PMID- 10909565
TI  - [Bureaucratic features of managed care].

PMID- 10909566
TI  - [Israel's ATLS program: summary and outlook].
AB  - In recent years a vigorous effort has been made to improve quality of primary
      trauma care in Israel. Advanced trauma life support courses (ATLS) were given to
      physicians throughout the country, regardless of their specialties. In 7 years
      4229 physicians participated in 202 courses with an average success rate of 76%.
      In the future, issues such as mandatory vs. voluntary training, language
      barriers, and continuous decline of knowledge should be addressed if momentum is
      to be maintained.

PMID- 10909567
TI  - [Screening tests for early detecting breast cancer in women in Israel-
      performance rates and patient characteristics].
AB  - Screening tests including mammograms for early detection of breast cancer are in
      the basket of services provided under the National Health Insurance Law. The law
      also defines the population groups entitled to mammograms, and sets the frequency
      of the test as once every 2 years. The aim of this study was to examine the
      screening rates for early detection of breast cancer at the inception of the law,
      in order to monitor future changes in performance rates, and identify the
      characteristics of those unlikely to undergo these tests, in order to promote the
      use of screening tests by them. This study is part of a comprehensive survey
      examining the effect of the National Health Insurance Law on the Israeli
      population. The survey, carried out in the summer of 1995, included a sample of
      1,400 Israeli residents aged 22 and over. To determine performance rates for
      clinical breast examinations a subgroup of 515 women aged 30 and over was
      sampled. To determine performance rates for mammograms, 173 women were aged 50-74
      (the entitlement ages under the law), were sampled. 54% of women aged 30+
      reported having had at least 1 clinical breast examination during their lifetime,
      and 56% of women aged 50-74 reported having had a mammogram during the past 2
      years. Variables with an independent effect on the likelihood of having had a
      clinical breast examination by a physician during the past 2 years were: being
      over the age of 50, having at least 9 years of education, being a veteran
      resident of Israel (as opposed to a new immigrant), and being Jewish. Variables
      with an independent effect on the likelihood of having a mammogram during the
      past 2 years were: being a veteran resident of Israel, and having a high income-
      which was found to have a borderline effect. The findings of the survey emphasize
      the importance of changing the behavior patterns of both women and physicians,
      informing women about their entitlement to the tests, and raising consciousness
      of the importance of having repeated clinical examinations by a physician, as
      well as mammograms.

PMID- 10909568
TI  - [Routine use of of two internal mammary arteries for coronary bypass grafting-
      one year experience at the Tel Aviv Medical Center].
AB  - The skeletonized internal mammary artery (IMA) is longer, and its immediate
      spontaneous blood flow is greater than that of the pedicled IMA, thus providing
      increased versatility for complete, arterial myocardial revascularization without
      the use of saphenous vein grafts. From April 1996 to May 1997, 583 patients
      underwent coronary artery bypass grafting here and in 415 (71%) complete arterial
      revascularization was achieved using bilateral skeletonized IMA. The right
      gastroepiploic artery was used in 57 (13%); there were 329 males (79%) and 86
      women (21%); average age was 64 (30-87) and 175 (36%) were older than 70; 131
      (32%) were diabetics. Average number of grafts was 3.2 (range 2-6 grafts). At 30
      days, 5 (1.2%) had died and there had been 6 perioperative infarcts (1.4%), 5
      CVA's (1.2%), and 6 had sternal wound infections (1.4%). Up to 1-12 months of
      follow-up was achieved in 409 (99%). Late mortality was 1.4% (of which 3 were
      noncardiac). 394 (97%) were angina-free at latest follow-up. We conclude that
      arterial revascularization using bilateral skeletonized IMA is safe, as
      postoperative morbidity and mortality are low, even in old and diabetic patients.

PMID- 10909569
TI  - [Characterization of the biological process of aseptic loosening of joint
      implants in orthopedics].
AB  - The purpose of orthopedic joint implants is to improve joint movement. Within the
      past 30 years, biomechanical improvements affecting the life-span of the implants
      has brought a new type of problem: the biological response to debris from the
      implant material contributes greatly to aseptic loosening of the prosthesis. The
      process is mediated by osteotropic factors, cytokines released from mononuclear
      cells, and osteoblasts and osteoclasts in the bone-cement interface or bone
      implant interface.

PMID- 10909570
TI  - [Percutaneous revascularization of the left main coronary artery as coronary
      artery bypass in high surgical risks].
AB  - Coronary artery bypass grafting is the treatment of choice for obstructive
      disease of the left main coronary artery. Its proximal location and easy
      accessibility make the left main artery an inviting target for percutaneous
      intervention, an approach contraindicated by the high associated risk. We
      describe 2 patients at high operative risk in whom the obstructed main coronary
      artery was successfully revascularized percutaneously. Coronary stenting and
      rotational ablation of calcified arteries are essential for successful outcome
      and minimize complications.

PMID- 10909571
TI  - [Treating hospitalized children in severe pain with oral methadone].
AB  - Pain relief is usually inadequate in hospitalized patients, especially in
      children, either after surgery or with various medical conditions. Among other
      reasons, this is due to suboptimal use of available analgesic drugs. In the past
      2 years oral methadone has become our opioid of choice for severe pain in
      hospitalized children who can take oral medication. More than 70 babies and
      children, aged 8 months to 9 years, who suffered mainly from pain due to burns or
      cancer, were treated by the in-hospital pain service. They received 0.1%
      methadone syrup, 0.2-0.4 mg/kg/day, for from a few days to more than a month. In
      most there was significant pain relief with no serious side-effects. In some,
      treatment could be changed to parent-controlled analgesia after a few days, with
      no adverse effects. We describe 5 of the children who present the advantages of
      oral methadone over other opioids.

PMID- 10909572
TI  - [Intradermal hepatitis B vaccination in workers not responsive to intramuscular
      vaccination].
AB  - Health care workers are at continuous risk of hepatitis B infection. Currently
      recommended intramuscular vaccination confers immunity in only 85-90%. We
      examined the immunogenicity and safety of intradermal vaccination of hepatitis B
      vaccine in nonresponders. 400 hospital employees who had been immunized as
      recommended were screened for anti-HBs antibodies and 50 were found seronegative.
      Each received an intramuscular booster injection and antibody level was measured
      a month later. Excluded were 33 employees, including 24 late responders, 2 HbsAg
      carriers and 7 uncooperative employees. 17 employees (mean age 47.1 yrs) then
      received a series of 3 intradermal injections of Energix B, 0.25 ml in the
      forearm, 2-3 weeks apart. The mean number of previous intramuscular injections
      was 4.6 +/- 1.4. A month later there was a mean titer of 315.4 +/- 347.0 miu/ml
      of antibody in 16/17 workers. Side effects were minimal. Intradermal injection of
      hepatitis B vaccine for nonresponders seems effective for inducing
      seroconversion. Its cost-effectiveness for the health care system warrants
      assessment.

PMID- 10909573
TI  - [Why do they leave? Clinical characteristics of patients who leave the emergency
      room against medical advice].
AB  - The object of this study was to characterize those who leave the emergency
      department against medical advice and to examine the short-term consequences. The
      study was conducted retrospectively during 1992 and prospectively during May
      August 1993 by telephone interviews. About 0.5% of all the patients who applied
      to the emergency department left against medical advice. Their main
      characteristics was that they were mostly young, single men. A wide range of
      complaints had brought them to the emergency department, very similar to that of
      the control group, but with a higher tendency to abuse drugs and alcohol. Most of
      those who left against medical advice had less severe disease than the controls.
      However 10% of them had to be hospitalized within the subsequent 2 weeks, in
      comparison with 4% of the controls. This study suggests that improving the
      efficiency of the emergency department will decrease the number leaving against
      advice.

PMID- 10909574
TI  - [Effect of an extract containing esterol on plasma cholesterol and oxidants].
AB  - 16 patients with hypercholesterolemia were treated with an extract of alpha-alpha
      leaves (esterol) while on a low-fat, low-cholesterol diet. Esterol is believed to
      inhibit the absorption of cholesterol and bile acids and may interfere with the
      absorption of essential nutrients. As oxidative modification of lipoproteins is
      required for the process of atherosclerosis, plasma antioxidant vitamins were
      followed. After 4 months of treatment, plasma cholesterol decreased by 10% from
      282 to 250 mg/dl (p < 0.001) and LDL cholesterol by 13%, from 203 to 177 mg/dl (p
      < 0.001). Plasma antioxidant vitamins E, A and beta-carotene were unchanged.
      Thus, esterol has a cholesterol-lowering effect but apparently does not lower fat
      soluble, plasma antioxidant vitamins. Both cholesterol-lowering and plasma
      antioxidant vitamins are important for the primary prevention of coronary artery
      disease in hypercholesterolemia.

PMID- 10909575
TI  - [Cardiac failure following sting of yellow scorpion in an adult].
AB  - 3 men, aged 18, 29, and 47 had severe cardiovascular disturbances following the
      sting of the yellow scorpion (Leiurus quinquestriatus hebraeus), which is
      considered the most dangerous scorpion in Israel. Cardiovascular complications
      are common in children after scorpion sting, but are rare in adults. Pulmonary
      edema developed in 1 of those being reported and hypertension and arrhythmias in
      the other 2. Severe deterioration in left ventricle function was confirmed by
      echocardiographic measurement of diminished ejection fraction. All patients
      recovered completely. This is the first report of severe cardiac involvement in
      adults following scorpion sting. We therefore recommend that even adults who
      develop cardiac symptoms after scorpion sting, particularly those with chronic
      cardiac disease, be monitored and treated in an intensive care unit.

PMID- 10909576
TI  - [Female genital mutilation].

PMID- 10909577
TI  - [Genetic defects in the Y chromosome causing defective spermatogenesis in
      infertile men].

PMID- 10909578
TI  - [Cryopreservation and transplantation of ovarian tissue as a means of preserving
      female fertility].

PMID- 10909579
TI  - [A new variant of Creutzfeldt-Jakob disease and its relation to bovine spongiform
      encephalopathy (BSE) in Great Britain].

PMID- 10909580
TI  - [Minimally invasive coronary grafting--fashion or breakthrough?].

PMID- 10909581
TI  - [Cellular test used to determine compatibility between bone marrow donor and
      recipient in HLA in identical twins].

PMID- 10909582
TI  - [Medical-legal assessment of the patient with dementia to prepare a will:
      statement of medical opinion].

PMID- 10909583
TI  - [Diarrheal diseases caused to enterotoxigenic Escherichia coli (ETEC)].

PMID- 10909584
TI  - [Emery-Dreyfuss dystrophy--update].

PMID- 10909585
TI  - [Is the drinking of cow milk in infancy a predisposing factor for insulin
      dependent diabetes mellitus?].

PMID- 10909586
TI  - [Protection from occupational tuberculous infection].

PMID- 10909587
TI  - [Chylothorax following penetrating injury].
AB  - We describe a 19-year-old man with 9 stab wounds of the chest. Initial evaluation
      revealed paraplegia at the D-10 level and bilateral hemothorax. 2 days after
      admission right-sided chylothorax was diagnosed. Fasting and total parenteral
      nutrition resulted in complete clearance. Chylothorax can cause major metabolic
      consequences, but prompt treatment results in full recovery.

PMID- 10909588
TI  - [Primary care physicians in Israel--compared with European countries].
AB  - This study compares Israeli primary care physicians with those of European
      countries. In Israel a larger proportion of those in primary care are women. The
      Israeli physicians see many patients a day, but almost never make home visits.
      They also report for work the fewest hours a day, but spend 21 hours a month in
      continuous medical education. (more than Europeans?) The Israeli primary care
      physician scores high in screening for breast cancer and blood cholesterol level,
      but very low in the fields of minor surgery and alcohol and smoking prevention,
      contraception, nutrition counseling and normal pregnancy follow-up. Residency
      training and education may be inadequate, and more emphasis has to be put on the
      health system and recognizing environmental influences.

PMID- 10909589
TI  - [Living-related liver transplantation--first experiences at Rabin Medical
      Center].
AB  - Our experience with living-related liver transplantation is described. In 2 boys
      and 1 girl, aged 4-4.5 years with acute, fulminating hepatitis A, the presence of
      very severe jaundice (bilirubin levels > 18 mg%) associated with severe
      coagulopathy (INR > 10) and encephalopathy indicated the need for urgent liver
      transplantation. In all 3 cases the left lateral hepatic segment of a matched
      blood type parent was transplanted. None of the donors suffered a serious
      complication postoperatively and all returned to full activity in 6-16 weeks. The
      post-transplantation course was uneventful in 1 child, but in the other 2 there
      was hepatic arterial thrombosis in 1 at 1 day and in the other at 8 days post
      transplantation. Early detection of arterial thrombosis by Doppler sonography
      permitted salvage of the 2 hepatic grafts after thrombectomy and re-anastomosis.
      In 1 of these 2 children an anastomotic biliary stricture was found 2 months
      after transplantation. It was corrected at surgery and a percutaneous stent was
      inserted. All 3 children are alive with normal graft function at 2, 7 and 8
      months post-transplantation, respectively. This initial experience indicates that
      living-related liver transplantation is feasible in Israel. The technique might
      help to solve our severe organ shortage for children awaiting liver
      transplantation.

PMID- 10909590
TI  - [Delirium tremens in Israel].
AB  - We discuss pathogenetic aspects (biochemical, pharmacological) of delirium
      tremens (DT) in accordance with the acute clinical processes, the development of
      psychosis, and preventive treatment used in the various stages. A typical
      patient, a 33-year-old man, and the difficulties in diagnosis and treatment are
      presented and conclusions from the dangerous behavior of the patient are drawn.

PMID- 10909591
TI  - [Nursing home-acquired pneumonia--guidelines for hospitalization].
AB  - To determine if there are any specific features of nursing-home acquired
      pneumonia we carried out a retrospective study in a nursing home between 1995
      1996, based on clinical and laboratory data. We found no correlation between
      these findings and the severity of pneumonia, so it would be hazardous to
      determine rigid guidelines. These patients should be treated in the nursing home
      as long as conditions allow, in order to avoid hospitalization.

PMID- 10909592
TI  - [Acute hyperparathyroidism caused by hemorrhage into a parathyroid adenoma].
AB  - Acute hyperparathyroidism is a rare and dangerous condition. It is supposed to
      result from transformation of a mild chronic form into an acute and stormy
      illness. The causes and the mechanism of such a transformation are usually
      unknown. A case of acute hyperparathyroidism is presented in which hemorrhage
      into a parathyroid adenoma was recognized and diagnosed as the immediate cause of
      the transformation from the mild long-standing form of the disease into the
      severe acute form.

PMID- 10909593
TI  - [Chemical synovectomy in arthritis by intra-articular injection of osmic acid].
AB  - 18 patients suffering from persistent synovitis despite medical therapy were
      treated with an intra-articular injection of osmic acid. After 1 year of follow
      up, 68% had good results and there were no complications nor detectable
      radiographic evidence of disease progression. Because osmic acid is almost as
      effective as surgical synovectomy and is cheap and easy to administer, it can be
      recommended as the first choice for treatment of corticosteroid-resistant
      arthritis in the early stages of the disease.

PMID- 10909594
TI  - [Suicidal calls to a telephone emergency service].
AB  - Suicidal threats and suicidal ideation among callers to the Israeli hot-line
      (ERAN) were investigated, using 2 methods of analysis. The first, an
      epidemiological survey based on 8,272 calls received by all 8 ERAN posts during 2
      years, reported on their standard form for recording interactions with suicidal
      callers. The second is content analysis of 42 detailed reports of interactions
      with such callers. Epidemiological analysis revealed a higher rate of suicidal
      ideation among callers with a psychiatric history, compared with those without a
      history. However, the 2 groups did not differ in rate of suicidal threats. In
      addition, suicidal threats of adolescents were related mainly to problems of
      identity and self-image, while mental disorders were the main problems among
      adults. Content analysis identified 2 patterns of terminating the interaction,
      which represent 2 strategies of intervention to prevent suicide. The first is
      establishing a contact between the caller and an appropriate individual in the
      caller's environment who undertakes responsibility to help the caller. The second
      strategy is reducing the caller's tension, leading to a withdrawal of the
      suicidal threat. The first pattern is more characteristic of interactions with
      psychiatric callers, while the second is more frequent among non-psychiatric
      callers to ERAN. The hot-line makes a unique contribution in helping those
      threatening suicide, which constitutes a real emergency.

PMID- 10909595
TI  - [Ketogenic diet--an alternative therapy for epilepsy in adults].
AB  - The ketogenic diet is an accepted alternative for children with intractable
      generalized or multi-focal seizures not amenable to surgery. It is not commonly
      used in adults because of the impression that the diet is less effective after
      childhood, when it is more difficult both to achieve ketosis and to change
      dietary habits. We present a 20-year-old man with intractable epilepsy since
      early childhood who is being treated with great success by a medium-chain
      triglyceride ketogenic diet. It has not only controlled the seizures but has also
      improved quality of life. We recommend a therapeutic trial of the ketogenic diet
      in intractable epilepsy for all ages.

PMID- 10909596
TI  - [Biological warfare and the medical profession].

PMID- 10909597
TI  - [Exposure to pesticides and breast cancer].

PMID- 10909598
TI  - [Rheumatic aspects of parvovirus B-19 infection].

PMID- 10909599
TI  - [Bacterial infections complicating influenza].

PMID- 10909600
TI  - [Treatment of battered women--a diagnostic and intervention challenge for the
      primary physician].

PMID- 10909601
TI  - [Domestic violence in pregnancy].

PMID- 10909602
TI  - [Prokinetic medication in gastroenterology].

PMID- 10909603
TI  - [Future treatment modalities in Duchenne muscular dystrophy].

PMID- 10909604
TI  - [Diagnostic and therapeutic approach to simple ovarian cysts in the
      postmenopausal woman].

PMID- 10909605
TI  - [The painful shoulder--differential diagnosis, assessment and treatment].

PMID- 10909606
TI  - [Angiotensin II--a local growth factor].

PMID- 10909607
TI  - [Medicine and religion].

PMID- 10909608
TI  - [Drowning in Israel--1990-1992].
AB  - There are no epidemiological studies of drowning in Israel in the scientific
      literature, despite prominent reports in the media. We analyzed the extent of
      mortality from drowning in Israel during 1990-92, attempting to identify and
      characterize groups at high risk, and to determine trends and differences between
      Israel and other countries. Computerized death certificate files were provided by
      the Israel government Central Bureau of Statistics; deaths from drowning were
      included among external causes codes E-830, 832, E-910, E-954, E-964, E-984. In
      Israel, as in the United States, mortality from drowning is the fourth cause of
      death among all unintentional causes, and the second cause in age-groups 1-24,
      ranking after transport accidents. During 1990-92 there were 1.2 drownings a
      year/100,000 population. The highest rates were found among young non-Jews 15-24
      years old (7.8/100,000) and among elderly Jews (3.5/100,000). Unintentional
      drowning accounted for 89% of all deaths; while about 10% were defined as
      suicides. Males had a rate almost 3 times greater than females, and the among
      Arabs was 2.4 times greater than among Jews. The 1990-92 drowning rate was
      slightly lower than in previous years. Drowning rates in Israel are lower than in
      the United States, except in the elderly. Apparently the principal reason for
      this difference is difference in sites of drowning. In Israel most drownings
      occur in the sea, so site data are unavailable for international comparisons.
      Careful consideration of the categories (E-codes) included in the rates, and of
      local registration procedures, is necessary for international comparisons.
      Foreign workers, tourists and other nonresidents are not included in national
      vital statistics. But estimations based on Ministry of Interior sources show that
      foreign workers (most, recent arrivals) during the last few years are an
      extremely high risk group. Population-based drowning rates are not an accurate
      estimation of drowning risk, since universal exposure to the "opportunity to
      drown" is assumed.

PMID- 10909609
TI  - [Evaluation of 452 patients with erectile dysfunction treated by combinations of
      vasoactive agents by penile injection].
AB  - In the past 15 years there has been continuous increase in the use of injections
      into the corpora cavernosa of different vasoactive drugs for treatment of
      erectile dysfunction (ED). However, some of these drugs are very expensive, are
      not available everywhere, and have side effects. We therefore compared the
      success rate of the most widely used compounds, papaverine and regitine, in 452
      patients (age range 26-85) with different types of ED. Each patient received in
      the clinic injections of papaverine, 6-25 mg, and regitine, 0.05-1.5 mg. When
      maximal rigidity of the penis (MRP) was > 80%, we instructed the patient to self
      inject the drug at home, 5-30 minutes before coitus. If after 3 injections MRP
      was not > 80%, prostaglandin E1 (PGE1) in an average dose of 10-25 mcg was added.
      If there was no response, papaverin + regitine + PGE1 were given in higher
      dosage, and atropine sulfate, 0.02 + 0.06 mg, was added if necessary. Of 452
      patients, 305 (67.4%) had MRP > 80% after 3 injections of papaverine plus
      regitine. The other patients received PGE1 in addition. This was helpful in 61
      patients (41.5%), while 55 (63.9%) required papaverine + regitine + prostin in
      higher doses. Of these, only 31 received papaverine + regitine + PGE1 + atropine
      sulfate. Of these, 20 (64.5%) reached MRP > 80%, and 11 (2.4%) MRP < 60. For
      these 11 patients, we recommended a penile prosthesis. Thus in 67.4% of the 452
      patients, papaverine + regitine injections were effective; in 41.5%, PGE1; in
      63.9%, papaverine + regitine + prostin + atropine sulfate. Only 11 (2.4%) did not
      react to intracorporeal injection. This progressive method of treatment enabled
      us to select the optimal dosage and combinations of compounds in 441/452 patients
      (97.5%) according to the severity of their dysfunction. During follow-up of 6
      months, spontaneous erections without injection were achieved in 115 (26.0%).

PMID- 10909610
TI  - [Islet autoantibody assays in type I diabetes: superiority of passage from use of
      ICA to traditional tests].
AB  - Islet cell antibodies (ICA) continue to serve as the basis of the principal
      serological test for definition of active autoimmunity of beta-cells. Its
      disadvantages are the need for human pancreatic tissue and difficulty in
      obtaining quantitative results. In the past decade biochemically-defined beta
      cell antigens were described, leading to the development of sensitive and
      specific autoantibody assays, to predict insulin-dependent diabetes mellitus
      (IDDM). We examined the value of combined biochemically-based serological assays,
      such as autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and
      ICA512 (ICA512A) to replace the traditional ICA assay. Blood samples of 114 newly
      diagnosed IDDM patients, aged 12 +/- 5 yrs (range 2 months-29 years) were tested
      for ICA (indirect immunofluorescence), IAA, GADA and ICA512A (radiobinding
      assay). The latter 2 assays were performed using recombinant human [35S]-labeled
      antigen produced by in vitro transcription/translation. We found that fewer sera
      scored positive for ICA and/or IAA (80.7%, 92/114) than for 1 or more of IAA,
      GAD, or ICA512 (88.6%, 101/114). We conclude that combined testing for IAA, GAD
      and ICA512 can replace the traditional ICA/IAA test to predict IDDM and is
      helpful in the differential diagnosis of insulin-dependent and noninsulin
      dependent diabetes.

PMID- 10909611
TI  - [Community-acquired pneumonia in the elderly--guidelines for hospitalization].
AB  - A prospective study was carried out among elderly patients with community
      acquired pneumonia to determine if there are any specific features that could
      help in deciding whether to hospitalize, or to treat in the community. We
      concluded that there is no correlation between clinical presentation of pneumonia
      and outcome, except for impairment of consciousness. Laboratory data showed a
      correlation between oxygen saturation in arterial blood, levels of hemoglobin and
      albumin, and outcome. Sputum culture was not helpful in deciding about diagnosis
      and treatment, which remain empiric. These patients should be treated at home if
      conditions permit. Recommendations are made for improving such conditions.

PMID- 10909612
TI  - [Emergency stenting for acute left main coronary artery closure during cardiac
      catheterization].
AB  - We report a case of acute closure of the left main coronary artery, a rare
      complication of diagnostic cardiac catheterization, treated by emergency stenting
      prior to aorto-coronary bypass surgery. We suggest encroachment of the Judkins
      catheter into a calcified left main ostium; with dissection and acute thrombosis
      of this segment, as the possible mechanism. Clinically, the patient's condition
      deteriorated to cardiogenic shock and loss of consciousness. Remarkably, there
      was no angiographic evidence of significant left main coronary artery disease,
      besides the presence of calcification in the proximal part of the left coronary
      system and ventricularization of coronary pressure at the time of engagement. We
      chose to slide quickly the angioplasty guidewire through the left main coronary
      artery, which allowed prompt mechanical recanalization and rapid restoration of
      coronary flow, with dramatic clinical and hemodynamic improvement. This
      relatively simple procedure allowed stenting the left main artery after brief
      predilation, and the patient came to by-pass surgery in excellent condition. The
      rationale for surgery in this case was the need for complete coronary
      revascularization because of significant 3-vessel coronary artery disease.

PMID- 10909613
TI  - [Evaluation of a local infant formula enriched with polyunsaturated fatty acids
      produced in Israel].
AB  - Polyunsaturated fatty acids (PUFA) are vital for the normal development of the
      brain and the eye retina in infancy. Breast milk contains significant amounts of
      PUFA, and compensates for their low production in infancy. Only recently a few
      companies with worldwide product distribution have started to enrich infant
      formula with PUFA. We evaluated the safety and clinical efficacy of a locally
      made PUFA-enriched infant formula, produced for the first time in Israel. 50
      normal, full term infants participated in a prospective, randomized double-blind
      study. Half received a regular whey-predominant infant formula (Materna Plus),
      and the other half a PUFA-enriched formula (Materna Premium), both produced in
      Israel, for 30 days. Evaluation included physical examination, growth parameters,
      stool analysis, daily parental questionnaires regarding infant behavior and
      defecation, and developmental assessment. There were no significant differences
      on comparing growth parameters, infant behavior, attacks of restlessness, gas
      severity, or stool characteristics in the 2 groups. There were no side effects or
      abnormal stool findings in either group, and no differences in developmental
      assessment at 3 months of age. We conclude that the locally-produced PUFA
      enriched infant formula is safe and clinically efficient. We assume that the lack
      of any effect on developmental indices is due to the relatively short exposure to
      the PUFA-enriched diet. Nevertheless, based on the recent literature, there is no
      doubt that PUFA supplementation is vital in improving infant brain and eye
      development.

PMID- 10909614
TI  - [Conversion total hip replacement after failed internal fixation of
      intertrochantric fracture].
AB  - Between 1933-1995, 16 patients underwent conversion-total hip replacement after
      internal fixation of an intertrochanteric fracture failed. Clinical results were
      unsatisfactory compared to primary total hip replacement. There was a high
      incidence of intra- and postoperative complications, including femoral fracture,
      wound infection, and aseptic loosening. This study should increase the surgeon's
      awareness of the difficulties encountered in conversion of failed
      intertrochanteric fractures to total hip replacement.

PMID- 10909615
TI  - [Intravenous lignocaine for chronic pain: an 18-month experience].
AB  - Intravenous injection of lignocaine relieves pain in animals with experimentally
      induced pain, and in man, mainly those with neuropathic pain. 106 patients were
      treated with intravenous lignocaine during a period of 18 months (212 treatment
      sessions). Blood pressure, heart rate and pain scores were continuously monitored
      after an intravenous bolus of lignocaine, 1 mg/kg, followed by continuous
      infusion of lignocaine, 5 mg/kg during 1 hour. There was significant pain relief
      after each session in most patients, lasting from a few hours to 4 weeks. There
      were no significant side effects. We present 2 of our patients. Due to its
      simplicity, efficacy and safety, intravenous lignocaine injection is recommended
      for those with neuropathic pain unrelieved by other therapeutic modalities.

PMID- 10909617
TI  - [Who should be included in the list of authors, where and why].

PMID- 10909616
TI  - [Necrotizing soft tissue infection].
AB  - The dramatic course of necrotizing soft tissue infection represents a medical
      emergency, since it is limb- and life-threatening. Most necrotizing soft tissue
      infections are caused by mixed aerobic and anaerobic Gram-negative and Gram
      positive organisms. Most case have been reported in immuno-compromised hosts
      after penetrating trauma or surgery. We describe a unique series of cases of
      necrotizing soft tissue infection. The mainstay of treatment is early and daily
      debridement of devitalized tissue and broad-spectrum antibiotics. Hyperbaric
      oxygen therapy should be considered.

PMID- 10909618
TI  - [Neuronal ceroid-lipofuscinoses--a group of storage diseases unknown or
      unrecognized in Jews].

PMID- 10909619
TI  - [Electromagnetic interference in the medical environment and its effect on
      permanent pacemaker function].

PMID- 10909620
TI  - [Neurological significance of glutamate receptors in the central nervous system].

PMID- 10909621
TI  - [Pathogenesis of hypertension in obesity].

PMID- 10909622
TI  - [Endothelial cells and preeclampsia of pregnancy].

PMID- 10909623
TI  - [Therapeutic approach to motor fluctuation in patients with Parkinson disease].

PMID- 10909624
TI  - [Evaluation for epilepsy surgery].

PMID- 10909625
TI  - ["Baby bottle tooth decay"--a risk to the teeth of babies and young infants].

PMID- 10909626
TI  - [The impact of anorexia nervosa and pregnancy on mother, fetus and newborn].

PMID- 10909627
TI  - [The approach to patients susceptible to malignant hyperthermia].

PMID- 10909628
TI  - ["The best of doctors to Hell" (a study from the source of the Sages)].

PMID- 10909629
TI  - [Use of Intranet in the hospital setting].
AB  - In the Intranet system, the organization uses technologies developed and applied
      in the Internet network world-wide. Hospitals can use Internet technologies to
      make hospital information systems more efficient by improving use of existing
      systems and by adding additional possibilities. Furthermore, the hospital can
      improve its relations with its customers and also bring the organization
      additional customers. Intranet implementation can be divided into the areas of:
      communication, managing and distributing information, and application linkage.
      Implementation must be modular, gradual and planned according to economic,
      technological and organizational aspects of the hospitals. By the Intranet,
      organizations can achieve benefits that include: improving communication array,
      availability of data and information, using existing information systems and
      their applications, enhancing customer satisfaction and saving costs of manual
      application systems.

PMID- 10909630
TI  - [Management of malignant bowel obstruction in terminal care--is home care
      possible?].
AB  - Malignant bowel obstruction occurs in about 10% of those with advanced abdominal
      cancer and in about 25% of those with advanced pelvic cancer. Such patients
      usually develop nausea, vomiting, constipation, abdominal dilatation and colicky
      pain. Traditional therapy consists of intravenous fluids and decompression by
      duodenal tube, gastrostomy or operation but postoperative mortality is high.
      Treatment requires hospitalization and therefore such patients have not been
      considered candidates for home care. Palliative medical techniques can cope with
      this syndrome and allow home care. Hypodermoclysis, non-prokinetic antiemetics
      like haloperidol and scopolamine, octeotride, corticosteroids, and narcotics for
      severe abdominal pain can alleviate symptoms. Medications can be combined and
      infused subcutaneously in a syringe driver and patients can remain with their
      families in their natural environment. Such techniques can give these patients
      who have short life expectancies reasonable quality of life.

PMID- 10909631
TI  - [Kimura's disease and angiolymphoid hyperplasia with eosinophilia-- on disease
      with different expressions?].
AB  - Kimura's disease is a rare angiolymphoid proliferative disorder of soft tissue
      characterized by subcutaneous swelling and a predilection for the head and neck.
      There are usually enlarged regional lymph nodes, eosinophilia and elevated
      sedimentation rate and IgE levels. A 26-year-old women with subcutaneous masses
      in the submandibular area is reported. The diagnosis of Kimura's disease versus
      angiolymphoid hyperplasia is discussed.

PMID- 10909632
TI  - [Familial occurrence of Ebstein anomaly].
AB  - Ebstein anomaly is a rare congenital disease which affects location, structure
      and mobility of the tricuspid valve, and right atrium and ventricle. Although
      most cases are sporadic, familial occurrence has been reported. We report 2
      brothers born with Ebstein anomaly. The parents were first degree cousins and
      there were 8 other children. 2 daughters were born with other congenital heart
      anomalies, 1 with ventricular septal defect and the other with severe pulmonary
      artery stenosis. We suggest that in some families, Ebstein anomaly is an
      autosomal dominant disease with different expression in the sexes.

PMID- 10909633
TI  - [Benign intracranial hypertension following minocycline].
AB  - A 15-year-old girl, who had been treated with minocyclin for acne for 2 months,
      was admitted for investigation of headache, nausea and papilledema. A space
      occupying lesion was ruled out by computerized brain tomography. The diagnosis of
      benign intracranial pressure (pseudo-tumor cerebri) was made because of elevated
      cerebrospinal fluid pressure with normal biochemistry and cytology.
      Tetracyclines, especially minocyclin, commonly used for treating acne in
      adolescents, can cause benign intracranial pressure.

PMID- 10909634
TI  - [Acute gastroenteritis caused by enterohemorrhagic E. coli O157:H7].
AB  - We report a 48-year-old man admitted for watery diarrhea, high fever, chills and
      abdominal cramps. Enterohemorrhagic E. coli O157:H7 was isolated. This new,
      dangerous pathogen causes dysentery and complications such as hemolytic uremic
      syndrome and thrombotic thrombocytopenic purpura. These complications can cause
      renal failure, neurological deficit and death. Recognition of E. coli O157:H7
      infection is important since it causes a rare and dangerous condition. To the
      best of our knowledge this is the first case reported in Israel.

PMID- 10909635
TI  - [Laparoscopic approach to perforated duodenal ulcer].
AB  - As laparoscopy becomes more prevalent, it is being used for a growing variety of
      abdominal operations, both electively and as emergency treatment. We describe our
      preliminary experience in laparoscopic repair of perforated duodenal ulcer. 2
      women and 2 men, aged 40-78 were operated over a period of 4 months and in all
      laparoscopic suture and omentopexy were performed with meticulous abdominal
      lavage. Despite somewhat longer operative time but a similar period of
      hospitalization, the easier post-operative course and fewer wound complications
      justify this technique. The effectiveness of medical treatment of peptic disease,
      and especially the anti-Helicobacter pylori regimen, supports the view that
      closure of the perforation is usually enough, and vagotomy is not needed.

PMID- 10909637
TI  - [Killing the viable fetus--feticide].

PMID- 10909636
TI  - [Importance of internal fixation for talar neck fractures].
AB  - Fracture of the talus, which articulates with 4 other bones in the ankle and
      foot, must be properly diagnosed, classified and treated to avoid the common
      complications of post-traumatic osteoarthritis and avascular necrosis. Knowledge
      of blood supply and anatomy is imperative, since the surgical approach must not
      damage the few vascular structures that remain intact after the trauma. We
      present 5 cases of fractures at the neck of the talus. All underwent internal
      fixation, 1 after closed reduction and 4 after open reduction. In all the results
      were satisfactory, although 1 patient developed avascular necrosis of the talar
      body.

PMID- 10909639
TI  - [Bone marrow transplantation for severe autoimmune diseases--treatment of choice
      or a treatment of no choice?].

PMID- 10909638
TI  - [Autologous stem cell transplantation breast cancer with distant metastases].

PMID- 10909640
TI  - [Prosthetic heart valves].

PMID- 10909641
TI  - [Aortomyoplasty--a surgical treatment for end-stage heart failure].

PMID- 10909642
TI  - [Surgical treatment for gastric carcinoma--the Japanese versus the western
      approaches].

PMID- 10909643
TI  - [Hypothermia and cerebral injuries].

PMID- 10909644
TI  - [Autopsy--its relevance in the modern era].

PMID- 10909645
TI  - [Sentinel node biopsy in breast cancer--a new method for diagnosis of axillary
      lymph node metastasis].

PMID- 10909646
TI  - [Anticoagulant therapy in atrial flutter].

PMID- 10909647
TI  - [Sexual function after traumatic brain injury].

PMID- 10909648
TI  - [Colorectal carcinoma: recommendations for screening and early detection].

PMID- 10909649
TI  - [Teaching geriatrics to medical students].

PMID- 10909650
TI  - [John Locke: physician, diplomat and philosopher].

PMID- 10909651
TI  - [Transurethral microwave thermotherapy for benign prostatic hypertrophy in
      patients with high risk for surgery].
AB  - The effectiveness of transurethral microwave thermotherapy (TUMT) for benign
      prostatic hypertrophy in poor surgical risk patients (ASA class IV) with
      indwelling catheters, was assessed. All had had an indwelling catheter for 1-12
      months. Removal of the catheter was possible in 14 out of the 24 (58.3%). Urinary
      peak flow rates were 12.2 +/- 3.5 ml/sec at 3 months of follow-up and post
      voiding residual urine volumes of less than 50 ml were recorded in 13 catheter
      free patients. Our data suggest that TUMT is an effective procedure for
      management of high risk patients with indwelling catheters in whom surgery or
      anesthesia are contraindicated.

PMID- 10909652
TI  - [Combined treatment of hepatic tumors by cryosurgery and resection: first
      results].
AB  - Cryosurgery is an old technique which is being used for hepatic tumors as an
      adjuvant to hepatic resection. We recently treated 7 patients with multiple
      malignant liver tumors, 5 of whom had colorectal metastases, 1 carcinoid
      metastases, and 1 multiple hepatic lesions of hepatocellular carcinoma. 6
      underwent combined liver resection and cryoablation of lesions in the remaining
      liver. In the 7th patient, only cryoablation was performed because hepatic
      resection was rejected and there was an extrahepatic metastasis. The advantages
      of this treatment are removal or destruction of all liver lesions found by any
      method, including intraoperative ultrasound examination, maximal preservation of
      normal liver parenchyma and that it is curative in patients inoperable by
      standard criteria.

PMID- 10909653
TI  - [Mechanism of primary hypertension].
AB  - We review various theories of the pathogenetic mechanisms of steroid-induced and
      essential hypertension. We investigated the possibility that a pathogenetic
      mechanism leading to glucocorticoid (GC)-induced hypertension or to
      mineralocorticoid (MC)-induced hypertension, or both, may be of critical
      importance in primary hypertension. We studied plasma levels of corticosterone
      (BK) and aldosterone (Aldo), and their concentrations in arterial and renal
      tissues of spontaneously hypertensive rats (SHR), a model of primary
      hypertension, and in the antecedent strain WKY rats as a normotensive control.
      Plasma levels of BK and Aldo were found to be normal and identical in SHRs and
      WKYs. Tissue (intracellular) levels of BK were more than double in SHRs than in
      WKYs. Subsequently we examined the activity of 11 beta-hydroxy steroid
      dehydrogenase (11-HSD) in both aortic and renal tissues of SHRs and WKYs. 11-HSD
      converts BK to the corresponding 11-keto compound, 11-dehydro-corticosterone
      (cpd.AK), which is inactive, in view of its inability to bind to the MC receptors
      (and also to the GC receptors). BK, the main glucocorticoid in the rat, as well
      as cortisol, have high affinity for the MC-receptor (MR). Normally BK or cortisol
      are present in 10(2)-10(3) times greater concentrations than Aldo in tissues
      possessing MR. The enzyme 11-HSD deactivates BK (or cortisol), thus protecting MC
      receptors in the MC target tissues from being activated by GC. When we examined
      arterial and renal tissue activities of 11-HSD in SHRs, the activity of 11-HSD
      was only one-third that found in the WKY rats. This explained higher levels of BK
      in the tissues of SHR, and suggested that decreased activity of 11-HSD is a
      pathogenetic factor for hypertension in SHRs. Thus, in a model of primary
      hypertension such as SHR, decreased activity of 11-HSD in the target tissues of
      MC appears to lead to glucocorticoid-induced mineralocorticoid hypertension.

PMID- 10909654
TI  - [Splenic artery aneurysm].
AB  - Splenic artery aneurysm is an uncommon form of vascular disease of unknown
      etiology. Its clinical importance is due to its high mortality, especially in
      pregnancy, when maternal mortality is 70% and fetal mortality 95%. Most cases of
      splenic artery aneurysm are asymptomatic and are diagnosed incidentally. We
      present a woman with incidentally diagnosed splenic artery aneurysm in whom the
      splenic artery and its aneurysm were resected.

PMID- 10909655
TI  - [Massive pulmonary embolism--summary of experiences with 13 patients].
AB  - Pulmonary embolism is a common event in hospitalized patients. In some cases it
      presents with hemodynamic collapse, indicating massive obliteration of the
      pulmonary vasculature and has a very grim prognosis; 2/3 of such patients die
      within 2 hours of onset of symptoms. We describe our experience in 13 patients
      with massive pulmonary embolism. An aggressive diagnostic and therapeutic
      approach, utilizing sophisticated imaging techniques, thrombolytic therapy and
      surgery, led to the survival of 8 of the patients. Our experience supports an
      aggressive approach in these seriously ill patients.

PMID- 10909656
TI  - [Renal tubular dysgenesis in upper and western Galilee].
AB  - Renal tubular dysgenesis (RTD) is a very rare malformation. 48 cases have been
      described, mostly in North America, Europe and Israel. Histopathological
      examination plays a key role in its diagnosis of RTD. We present the results of a
      retrospective study documenting the frequency, clinical manifestations and
      pathological findings in RTD in the Upper and Eastern Galilee. In 343 perinatal
      autopsies performed in Safed and Nahariya Hospitals between 1974 and 1997, there
      were 5 cases with RTD. All were men, 3 were Druze and 2 were Jews. The parents of
      the Druze patients were first cousins; 2 cases were twins of whom 1 had RTD;
      intrauterine growth retardation was documented in 2 and oligohydramnios in 3
      cases. Life span of 4 newborns ranged from 1.1 to 49 hours and was complicated by
      severe respiratory failure and anuria. Ultrasound and postmortem examinations
      revealed no pathology of the kidney and urinary tracts. Absence of the proximal
      tubules was supported by immunohistochemistry for epithelial membrane antigen.
      Our previous assumption about the importance of lysozyme immunostaining for
      diagnosis of RTD was confirmed by this larger series of cases and by statistical
      analysis. Because RTD is considered an autosomal recessive phenotype with a
      recurrence rate of 25%, there should be genetic counseling of the family in every
      case of RTD.

PMID- 10909657
TI  - [Popliteal vascular trauma].
AB  - 6 cases of popliteal vascular trauma are presented, 3 due to posterior
      dislocation of the knee and 3 due to crush injury. The patients were referred
      from another hospital and some had undergone unnecessary angiography when
      ischemia was present, leading to delay in surgery. All patients presented with
      distal ischemia and underwent reconstructive surgery; 2 subsequently underwent
      below-knee amputation because of irreversible ischemia and sepsis. Urgent
      operation for popliteal vascular trauma is necessary whenever there is ischemia
      and intraoperative angiography may be necessary. There should be reconstruction
      of the artery and vein when there is concomitant venous damage, and fasciotomy
      and debridement are important. The harmful potential of occult popliteal vascular
      injuries and their ostensible mild presentation present a challenge for the
      emergency room surgeon.

PMID- 10909658
TI  - [Treatment of alcohol-withdrawal syndrome].

PMID- 10909659
TI  - [Antiphospholipid autoantibodies and reproduction].

PMID- 10909660
TI  - [Cytomegalovirus and atherosclerosis].

PMID- 10909661
TI  - [Preservation of ovarian function and fertility in women and men undergoing anti
      cancer therapy].

PMID- 10909662
TI  - [Heart rate variability, frequency domain analysis: use and applications in
      psychiatry].

PMID- 10909663
TI  - [Perineal approach to radical prostatectomy for organ-confined cancer].

PMID- 10909664
TI  - [Behavioral neurotoxicology--a developing field in occupational medicine].

PMID- 10909665
TI  - [The geriatric day hospital--past, present, future].

PMID- 10909666
TI  - [The family physician and prevention of alcohol-related problems].
AB  - Involvement of the family physician in the prevention of alcohol-related problems
      is described. Advice about risks in low-risk drinking is presented, as well as
      non-laboratory assessment of alcohol-dependency and of patients with increased
      risk of developing alcohol-related problems. The CAGE questionnaire, patterns of
      alcohol intake, and brief intervention among low-risk and high-risk patients are
      discussed.

PMID- 10909667
TI  - [The first medical appraisal: Rothschild and health services in early settlements
      and the medical network at the end of the 19th Century in Palestine].

PMID- 10909668
TI  - [Alcohol and trauma].

PMID- 10909669
TI  - [Laser injuries on the battlefield].

PMID- 10909670
TI  - ["The right to death with dignity"--in Holland: what are the dangers?].

PMID- 10909671
TI  - [Dr. Francois Rabellais: monk, physician, laughing philosopher and writer].

PMID- 10909672
TI  - [XVI Brazilian Congress of Clinical Neurophysiology. XXIV Meeting of the
      Brazilian League of Epilepsy. Sao Paulo, Brazil. 30 October-2 November 1999.
      Abstracts].

PMID- 10909673
TI  - 2000 Society for Academic Emergency Medicine (SAEM) annual meeting. San
      Francisco, California, USA. May 22-25, 2000. Abstracts.

PMID- 10909675
TI  - 669th Meeting, University of Keele. Abstracts.

PMID- 10909674
TI  - American Society of Hypertension 15th scientific meeting. May 16-20, 2000.
      Abstracts.

PMID- 10909676
TI  - 35th Meeting of the Canadian Congress of Neurological Sciences. Ottawa, Ontario,
      Canada. June 13-17, 2000. Abstracts.

PMID- 10909677
TI  - Canadian Ophthalmological Society annual meeting. Whistler, British Columbia,
      Canada. June 17-20, 2000. Abstracts.

PMID- 10909678
TI  - XX Congress of the International Society for Analytical Cytology. Abstracts.

PMID- 10909679
TI  - Outcome Measurements in Physical Medicine and Rehabilitation--Standard and
      Future. Vienna, Austria, December 1998. Abstracts.

PMID- 10909680
TI  - DMW/ISSX 2000 Meeting. The Drug Metabolism Workshop/International Society for the
      Study of Xenobiotics. St. Andrews, Scotland, June 11-16, 2000. Abstracts.

PMID- 10909681
TI  - 3rd Meeting of the International Society for Medical Gases (ISMG). Heidelberg,
      Germany, 29 September-1 October 1999. Abstracts.

PMID- 10909682
TI  - Euro-Neuro 2000: 2nd International Update on Neuro-Anaesthesia and Neuro
      Intensive Care. Genk, Belgium, 2-5 February 2000. Abstracts.

PMID- 10909683
TI  - XVth Congress of the European Association of Urology. Brussels, Belgium, April 12
      15, 2000. Abstracts.

PMID- 10909685
TI  - 3rd Symposium on the Control of Surgical Infections. Florence, Italy, April 14
      16, 1999. Abstracts.

PMID- 10909684
TI  - NCI-EORTC. From Discovery to Clinical Practice: Diagnostics Innovation,
      Implementation, and Evaluation. Nyborg Strand, Denmark, June 28-July 1, 2000.
      Abstracts.

PMID- 10909686
TI  - EUROPERIO 3. Geneva, Switzerland, June 8-11, 2000. Abstracts.

PMID- 10909687
TI  - International Congress 2000, 13th Annual International Congress on Endovascular
      Interventions.

PMID- 10909688
TI  - 11th Asian Pacific Congress of Gastroenterology and 8th Asian Pacific Congress of
      Digestive Endoscopy. Hong Kong, China, March 10-14, 2000. Abstracts.

PMID- 10909689
TI  - American Spinal Injury Association 25th annual meeting. Atlanta, Georgia, USA,
      April 19-21, 1999. Abstracts.

PMID- 10909690
TI  - International Symposium on Spinal Cord Injury: Neurobiology and New Therapeutic
      Approaches. Aachen, Germany, March 24-27, 1999. Abstracts.

PMID- 10909691
TI  - 139th Meeting of the Acoustical Society of America. Atlanta, Georgia, USA. 30 May
      3 June 2000. Abstracts.

PMID- 10909692
TI  - American College of Sports Medicine 47th annual meeting. Indianapolis, Indiana,
      USA. May 31-June 3, 2000. Abstracts.

PMID- 10909693
TI  - International Conference 1999: Basic and Therapeutic Aspects of Botulinum and
      Tetanus Toxins. Orlando, Florida, USA. November 16-18, 1999. Abstracts.

PMID- 10909694
TI  - [Society of Nephrology and Francophile Society of Dialysis 2nd joint meeting.
      Tours, France, 21-23 June 2000. Abstracts].

PMID- 10909695
TI  - 6th Annual meeting of the Organization for Human Brain Mapping. San Antonio,
      Texas, USA. June 12-16, 2000. Abstracts.

PMID- 10909696
TI  - 5th International Conference on Functional Mapping of the Human Brain.
      Dusseldorf, Germany, June 22-26, 1999. Abstracts.

PMID- 10909697
TI  - Neuroreceptor Mapping 2000 Conference. The 3rd International Symposium on
      Functional Neuroreceptor Mapping of Living Brain. New York City, New York, USA.
      June 9-11, 2000. Abstracts.

PMID- 10909698
TI  - North American Society of Pacing and Electrophysiology (NASPE) 21st annual
      meeting. Washington, DC, USA. May 17-20, 2000. Abstracts.

PMID- 10909699
TI  - 2000 American Alliance of Health, Physical Education, Recreation, and Dance
      National Convention (AAHPERD). Orlando, Florida, USA. March 21-25, 2000.
      Abstracts.

PMID- 10909700
TI  - [4th Congress of Pneumology of the French Speaking Languages. Nice, France, 26-29
      January 2000. Abstracts].

PMID- 10909701
TI  - SCANNING 2000. San Antonio, Texas, USA. May 9-12, 2000. Abstracts.

PMID- 10909703
TI  - Associated Professional Sleep Societies 14th annual meeting. Las Vegas, Nevada,
      USA. June 17-22, 2000. Abstracts.

PMID- 10909702
TI  - 87th Annual Congress of the Swiss Society of Radiology. Berne, Switzerland, 11-13
      May 2000. Abstracts.

PMID- 10909704
TI  - Surgical versus interventional procedures in patients with multivessel coronary
      artery disease.
AB  - OBJECTIVE: This study examined the clinical characteristics, risk factors,
      indications and post-intervention complications of patients with multivessel
      coronary artery disease (CAD) submitted to either percutaneous transluminal
      coronary angioplasty (PTCA) and/or stent placement versus isolated coronary
      artery bypass grafting (CABG). BACKGROUND: Several studies have examined the
      relative safety and outcome of patients submitted to those interventional
      procedures compared to CABG. Limited information is available regarding that
      subject in Puerto Rico. METHODS: We performed a retrospective analysis of the
      clinical, angiographic, operative, interventional, post-operative and post
      interventional data of patients submitted to those procedures in our institution
      from January 1998 to August 1998. There were 53 patients in the interventional
      group and 206 patients in the CAGB group. Comparison of quantitative variables by
      procedure was based on Student t test or Mann-Whitney-Wilcoxon test; categorical
      variables were compared using Pearson's chi-square or Fisher's exact test.
      RESULTS: There were no significant differences in age, body surface area, or
      cardiac risk factors. The most common pre-existing cardiovascular diagnosis was
      unstable angina. Three-vessel disease was the most common angiographic finding
      among CABG patients (61.7%). Two-vessel disease without left anterior descending
      coronary artery obstruction was significantly more common in the PTCA/Stent
      patients (58.5%). The vast majority (97.6%) of patients in the PTCA/Stent group
      and 52.4% of the CABG group had two-vessel intervention. A significantly higher
      frequency of complications occurred in the CABG group. However, the incidence of
      major complications, in both groups was not statistically different. Atrial
      arrhythmias were significantly more frequent in the CABG group. CONCLUSION: A
      larger prospective study should be conducted in order to corroborate these
      preliminary findings and seek effective solution to any identifiable problem.

PMID- 10909705
TI  - Intermittent infusion of inotropes in the outpatient setting: one-year post
      treatment analysis.
AB  - The course of patients with New York Heart Association (NYHA) class III and IV
      and refractory heart failure symptoms is characterized by progressive clinical
      deterioration and frequent hospital readmissions. The value of intermittent
      intravenous administration of inotropes in managing this group of patients in the
      outpatient setting has been controversial. In this study, patients with
      refractory heart failure symptoms were enrolled to assess the impact of a
      multidisciplinary outpatient program in terms of on hospital admissions,
      emergency room visits, and interval free of symptoms after administration of
      inotropes. This is a retrospective analysis on 41 patients with refractory heart
      failure treated at our outpatient cardiac infusion unit over a 20 month period.
      Thirteen patients with a NYHA class III [age 64 +/- 13; LVEF 27 +/- 9%] and 28
      patients with a NYHA class IV [age 65 +/- 13 years; LVEF 21 +/- 9%], mostly
      males, were included. A total of 65 admissions for decompensated HF were recorded
      in the previous 6-months prior to initiation of the outpatient program; compared
      to only 4 emergency room visits and 7 hospital admissions after enrollment.
      Furthermore, 17 patients have been discharged with improvement in NYHA class from
      3.5 +/- 0.6 to 1.4 +/- 0.5. On these patients, the interval free of symptoms
      since the last infusion treatment has ranged from 201 to 489 days, without
      emergency room visits or hospital admissions for congestive heart failure. The
      results of this study support the use of intermittent infusion of inotropes in
      the outpatient setting. Although the natural history for patients with refractory
      heart failure has been grim; the use of these intermittent infusions may in fact
      alter the natural course of end stage congestive heart failure patients and
      deserves further investigation.

PMID- 10909706
TI  - Perioperative outcomes in octogenarians undergoing cardiac surgery in Puerto
      Rico.
AB  - With the advances in surgical techniques and the advent of an aging population,
      the application of cardiac surgeries has broadened to include those patients over
      the age of 80. In order to characterize the in-hospital morbidity and mortality
      of elderly patients undergoing cardiac surgery at our cardiovascular center, a
      retrospective review of all medical records of consecutive octogenarian patients
      was made. Between January 1998 and April 1999, 76 patients (mean age (SD), 82.5
      (2.6)) underwent cardiac surgery, of which, 61.8% were males. Surgical procedures
      consisted of isolated coronary artery bypass grafting (CABG) in 64 patients,
      isolated aortic valve replacement (AVR) in 4 patients, combined CABG and left
      carotid endarterectomy in 4 patients, combined CABG and AVR in 2 patients,
      combined CABG and aortic aneurysm repair in 1 patient and combined AVR and aortic
      dissection repair in 1 patient. Surgery was elective in 51.3% of patients and
      seventy-one percent (54) experienced at least one postoperative complication. The
      most common complication was atrial arrhythmia (28) followed by low cardiac
      output (23) and pneumonia (16). Hospital mortality occurred in 11 (14.7%)
      patients, an estimate in agreement with previous published studies on
      octogenarians. Since the number of patients studied was small, these results
      require confirmation by other cardiovascular centers in the island. Further
      research to determine independent predictors of postoperative morbidity and
      mortality, to assess survival and quality of life after cardiac surgery and to
      evaluate cost-effectiveness considering new trends in managed health care is
      warranted.

PMID- 10909707
TI  - Characteristics of cancer patients under age 20 at a population-based registry,
      Puerto Rico, 1980-1991.
AB  - OBJECTIVES: To evaluate and describe the characteristics and incidence of
      pediatric (< 20 years) cancer in Puerto Rico between 1980-1991. METHODS: A
      descriptive study of all new childhood cancer cases among residents of Puerto
      Rico reported to the Cancer Registry between the years 1980 and 1991 was
      conducted. The distribution of cases was described by age, gender, place of
      residence, histology, last date known to be alive, and stage of disease.
      Incidence rates and standardized incidence rates by age were calculated. RESULTS:
      A total of 1,823 new pediatric cases were reported from 1980 through 1991. Over
      half were males, and 52.2% were aged < 10 years. Most cases resided in urban
      areas. The most frequent histologic types were leukemia (31.0%), lymphomas and
      other reticulo-endothelial neoplasms (16.2%), and brain, central nervous system,
      and intracranial and intraspinal neoplasms (16.0%). The most frequent type of
      tumor was acute lymphocytic leukemia (22.0%). Although the overall distribution
      of most neoplasms was similar between genders, a higher proportion of lymphomas
      was reported among males, and there were significantly more carcinomas among
      girls. The largest increase in the age-adjusted incidence rate between periods
      (1980-84 and 1985-89) occurred in the 5-9 age group. CONCLUSIONS: Overall, these
      findings are consistent with previous studies in USA. However, there were some
      differences in the distribution of histologic types when compared with similar
      studies in other countries, and with the results of the National Cancer
      Institute's Surveillance, Epidemiology and End Results (SEER) Program. Factors
      such as differences in diagnostic capabilities among countries must be taken into
      consideration.

PMID- 10909708
TI  - Drug release from Carbomer 934 matrices.
AB  - The main objective of this investigation was to describe the mechanism of drug
      release from Carbomer 934 hydrogel matrices and to evaluate the effect of polymer
      level, diluent type, and matrix restriction using customized device (that permits
      only one surface of the tablet to be exposed to the dissolution medium) on
      theophylline release from Carbomer matrices. Formulations containing theophylline
      (10%), Carbomer (10%, 30, 50%), direct compressible diluent (lactose fast flo,
      Avicel PH-101, Emcompress) and magnesium stearate (0.75%) were compressed at a
      target tablet weight of 450 mg and target hardness of 7-9 Kp. USP Apparatus 1,
      was used to test the drug release and Korsmeyer equation was used to describe the
      mechanism of drug release from Carbomer matrices. Results show that the release
      profile and release mechanism from Carbomer matrices were influenced by Carbomer
      level, diluent type, and matrix restriction. In general the release mechanism was
      anomalous (non-Fickian) except for 10% and 30% Carbomer level and in Avicel PH
      101 matrices, where, the release mechanism appears to follow super case II where,
      the n exponent has value greater than 0.89. All formulations selected appear to
      follow zero order release only up to 120 minutes. Restriction of tablet surface
      resulted in a shift toward Fickian release. This study demonstrated that it is
      possible to modify the drug release mechanism and rate, by changing polymer
      level, diluent type, and imposing physical restriction on the surface of the
      matrix.

PMID- 10909709
TI  - [Diagnosis of health needs of the elderly population of a community of Puerto
      Nuevo].
AB  - The purpose of this study was to identify the health needs of the non
      institutionalized population, 65 years and over, residing in a sector of the
      community of Puerto Nuevo. This was the first urbanization established in Puerto
      Rico in the early 50's. The "snowball" technique was use to identify all the
      residents 65 year and over of the mentioned sector. Eighty five elderly persons
      were interviewed to gather data of the following variables: demographics, health
      conditions, preventive measures, activities of daily living (ADLs, IADLs), health
      services utilization, psychosocial aspects and use of programs and services
      available for the elderly population. Statistical analysis included descriptive
      measures and chi-square. Results revealed a population with a higher education
      and economic level than the average for this age group in Puerto Rico. People
      over 75 years over reported more functional limitations than the 65-74 years
      interviewees did. In comparison with men, women were less educated and presented
      a higher percent of widows, persons living alone and functional limitations. In
      almost all the interviewees, help was available in case of need. The majority
      expressed satisfaction with their family and social lives. Very few utilized
      programs and services available for elderly persons. It is concluded that in
      order to improve their quality of life, this population needs to be managed in an
      holistic mode to address their biopsychosocial needs and to be educated in health
      promotion issues to prevent further functional limitations. They also need
      education about the available services for elderly persons.

PMID- 10909711
TI  - [Alternative methods of statistical analysis in epidemiology: frequency,
      likelihood, and Bayesian].

PMID- 10909710
TI  - [Ethical aspects of human lactation and breastfeeding].
AB  - Breastfeeding has experienced a surge in Puerto Rico thanks to the efforts of
      many women, as well as governmental, non-governmental and private organizations.
      Among the aspects which can affect the initiation, establishment and maintenance
      of successful breastfeeding one finds potential ethical conflicts among health
      professionals as well as the financial interests of the companies which produce
      and market artificial milks. These companies dedicate great marketing efforts and
      enormous sums of money in the sale of their products, in detriment of
      breastfeeding. The profit motive of these companies is in open contradiction to
      public health and to breastfeeding promotion. The international community has
      carried out efforts for more than two decades in the creation of structures which
      protect the rights of women and their children to ideal nutrition practices, free
      from commercial pressures, through breastfeeding. Possible ethical conflicts
      related to the new industry of breastfeeding paraphernalia are discussed,
      especially when these are marketed exclusively for profit. Recommendations are
      presented for health professionals in order for them to be able to face and
      respond to the unethical strategies practiced by the manufacturers of artificial
      milks in utilizing these professionals for legitimating and marketing their
      products.

PMID- 10909712
TI  - [Contributions of anthropology to an ethical approach to aging].
AB  - This article summarizes a presentation on the meanings and implications that
      crossing the old-age threshold has on the self-perception of the older adult. It
      draws from anthropological studies on the meaning of old age and sickness in old
      age that emphasize that meaning in old age for the older adult is the outcome of
      his/her considerations on aging in terms of individual experiences and the
      continuity of identity amidst the social and biological changes associated with
      old age. Implications for decision-making about medical treatment, the right to
      privacy, and the right to receive care in the less-restrictive possible
      environment for patient autonomy as well as interpretations about self-respect
      and self-determination are discussed.

PMID- 10909713
TI  - Ethical issues in nutritional sciences for the next century: nutrition research
      and counseling on nutraceutical supplementation and disease.
AB  - Ethical issues pertaining research and counseling in nutritional sciences will be
      arising in this new century. This issue will be of great importance especially in
      the area of nutraceutical supplementation and disease (pharmacological
      nutrition). Steps to insure bioethical correctness are discussed in this paper.

PMID- 10909715
TI  - [Pharmacology as a moral enterprise].

PMID- 10909714
TI  - Pigmented lesion of the oral cavity with eight years follow-up.
AB  - A 27 year old white female with a pigmented lesion on the anterior portion of the
      mandibular gingival is described. A prophylactic excisional biopsy was performed
      in conjunction with a gingival graft. A gingival graft was performed to
      accelerate the healing process and reduce post operative discomfort. An
      intradermal nevus was diagnosed. The number of documented oral nevi in the
      literature now exceeds 200 and approximately half of them are histologically of
      the intradermal type. If early detection of thin oral melanomas is to be
      achieved, all pigmented oral cavity lesions should be viewed with suspicion.

PMID- 10909716
TI  - [Late sequelae of early summer meningoencephalitis].
AB  - The incidence of tick-borne encephalitis varies widely in different geographic
      regions due to local difference in the rate of infected vectors (Ixodes ricinus)
      transmitting tick-borne encephalitis virus. In the Cantonal Hospital Winterthur a
      large number of cases are hospitalised due to endemic areas with infected ticks
      nearby. From 1976 until 1996 132 patients with tick-borne encephalitis were
      hospitalised (an average of 7 patients per year), compared with 535 cases (41 per
      year) in the whole of Switzerland during a similar period (1984-1992). While
      previously tick-borne encephalitis was considered to be a harmless illness with
      complete recovery, a postencephalitic syndrome after tick-borne encephalitis has
      recently been reported. Since the prevalence of sequelae differs in these
      publications, the aim of this study was to investigate sequelae in a Swiss
      population which had suffered from tick-borne encephalitis. We retrospectively
      analysed the patients with tick-borne encephalitis hospitalised in the years 1987
      1996, to determine the clinical and functional outcome. A few weeks after
      discharge from hospital, 73% patients still had complaints, and one year later
      56%. 32 patients were observed over 5 years and 31% still had some disability.
      After tick-borne encephalitis 10% of patients did not recover the same quality of
      life as before. The symptoms most frequently reported were fatigue, concentration
      deficits and impairment of memory. Objective neurological deficits were rare. Our
      results correspond well with experience in other countries and demonstrate the
      substantial morbidity of tick-borne encephalitis. We recommend therefore
      vaccination against tick-borne encephalitis, an effective measure with a low
      complication rate.

PMID- 10909717
TI  - [Patient self-monitoring of oral anticoagulation with CoaguChek].
AB  - We investigated the feasibility, quality and safety of patient self-control of
      oral anticoagulation. The patients were selected by their physicians on the basis
      of criteria such as compliance, skills and motivation. After theoretical and
      practical training they self-monitored and self-adjusted their anticoagulant
      dosage for 6 months by weekly self-measurement of their INR values using a
      capillary whole blood prothrombin time monitor (CoaguChek). Venous INR
      measurements once a month served as quality control. There were 51 study
      participants, who performed a median 5 INR measurements per month. 75.8% of all
      registered INR values were within the recommended individual INR target ranges.
      The coefficient of correlation between capillary (y) and venous (x) INR values
      was r = 0.87 (regression analysis y = 1.0 x -0.2). The concordance of capillary
      and venous INR values was 80% with respect to the individual INR target ranges.
      There were 5 minor bleeding episodes and no overt thromboembolic recurrences
      during the study period. In conclusion, the study demonstrated that patient self
      control of oral anticoagulation is feasible and achieves a high percentage of INR
      values within the recommended target ranges. Therefore, self-control of oral
      anticoagulation can be offered to skilled and motivated patients as an
      alternative to physician-guided antiocogulation. However, specific training of
      these selected patients is necessary.

PMID- 10909718
TI  - [Fulminant liver failure in anamnestic morbid obesity].
AB  - Jejunoileal bypass was an effective method of treatment for weight reduction in
      severe cases of obesity. However, long-term follow-up revealed serious and even
      lethal side-effects, e.g. acute liver failure, as shown in a case report of a
      patient who died 28 years post-operatively of acute liver failure as a direct
      result of liver cirrhosis. We therefore conclude that jejunoileal bypass should
      no longer be performed, especially as better methods, such as gastric banding,
      exist. Patient care and monitoring is highly important and, if feasible, the
      bypass procedure should be reversed.

PMID- 10909719
TI  - [In search of strategies for preventing brain damage as a sequela of bacterial
      meningitis].
AB  - Multiplication of bacteria within the central nervous system compartment triggers
      a host response with an overshooting inflammatory reaction which leads to brain
      parenchyma damage. Some of the inflammatory and neurotoxic mediators involved in
      the processes leading to neuronal injury during bacterial meningitis have been
      identified in recent years. As a result, the therapeutic approach to the disease
      has widened from eradication of the bacterial pathogen with antibiotics to
      attenuation of the detrimental effects of host defences. Corticosteroids
      represent an example of the adjuvant therapeutic strategies aimed at
      downmodulating excessive inflammation in the infected central nervous system.
      Pathophysiological concepts derived from an experimental rat model of bacterial
      meningitis revealed possible therapeutic strategies for prevention of brain
      damage. The insights gained led to the evaluation of new therapeutic modalities
      such as anticytokine agents, matrix metalloproteinase inhibitors, antioxidants,
      and antagonists of endothelin and glutamate. Bacterial meningitis is still
      associated with persistent neurological sequelae in approximately one third of
      surviving patients. Future research in the model will evaluate whether the
      neuroprotective agents identified so far have the potential to attenuate learning
      disabilities as a long-term consequence of bacterial meningitis.

PMID- 10909720
TI  - [Periorbital hemorrhage in amyloidosis].

PMID- 10909721
TI  - [Special problems after lung transplantation: walking a tightrope between
      infection and graft rejection].
AB  - Between November 1992 and September 1999 84 lungs have been transplanted at
      University Hospital Zurich. Currently the 1-year survival rate is up to 85%.
      However, long-term success is limited by the development of chronic rejection in
      the form of bronchiolitis obliterans. The risk factors are repeated episodes of
      acute rejection and infections, due to cytomegalovirus in particular. Both can
      occur in asymptomatic patients and are sometimes detected only by transbronchial
      lung biopsy. At the Zurich Lung Transplant Centre biopsies are performed as
      surveillance biopsies in asymptomatic patients in the first 6 months after
      transplantation, for clinical indications and as follow-up biopsies after a
      pathological result. Open lung biopsies are performed for special indications
      only. We evaluated 408 transbronchial biopsies taken between November 1992 and
      September 1999. Relevant findings were present in 46% of biopsies in symptomatic
      patients. Relevant acute rejection episodes were diagnosed in 15% of surveillance
      biopsies. Overall, 72% of acute rejection episodes requiring therapy and 33% of
      biopsies detecting cytomegalovirus were found in surveillance biopsies. 7 of 11
      late (> 45 days postoperative) and 1 of 5 early (< or = 45 days postoperative)
      open lung biopsies revealed new diagnoses. Transbronchial biopsy after lung
      transplantation is at present the gold standard for diagnosis of acute rejection
      and cytomegalovirus pneumonia of the lung.

PMID- 10909722
TI  - [Kidney transplantation: what does biopsy contribute?].
AB  - Kidney biopsy is an important diagnostic tool for the evaluation of kidney
      transplantation. Histological evaluation of the donor kidney serves to identify
      risk factors for recurrent disease, neoplasia and/or graft failure due to
      numerous factors such as damage to the donor kidney during surgical removal or
      implantation, injury sustained during the transport process between the donor and
      recipient, and less than optimal allograft perfusion during the intra- and
      postoperative period. The most important question for the pathologist is the
      cause of renal dysfunction (rejection) after transplantation. The value of renal
      allograft biopsy has been significantly enhanced by several developments:
      improved, internationally accepted classification of kidney transplantation
      pathology (Banff 1997) and the development of molecular biological techniques
      such as RT-PCR evaluation of perforin, granzyme B and Fas ligand, which can be
      applied to renal allograft tissue to obtain a diagnosis of acute rejection with
      high sensitivity and specificity, are very promising but not used in routine
      diagnosis.

PMID- 10909723
TI  - [Heart transplantation: life-long biopsies for prevention of rejection?].
AB  - The transplantation of a heart restores the quality of life and productivity to
      patients who have experienced severe loss of contractility of heart muscle during
      an infection or as a result of long-lasting chronic heart disease. Monitoring for
      allograft rejection requires expensive procedures whereby, with catheterisation
      of the right heart, endomyocardial biopsies are retrieved. Evaluation by the
      pathologist uses a standardised diagnostic scheme which is in use worldwide. We
      have tested the interobserver agreement in a very heterogeneous group of
      examining pathologists and found moderate agreement with a kappa value of 0.52.
      The development of other methods to improve and even to replace invasive
      procedures for monitoring acceptance/rejection of a cardiac allograft requires
      interdisciplinary cooperation.

PMID- 10909724
TI  - [Liver transplantation and tumors: risk and chance].
AB  - Liver transplantation is the established therapy of choice for endstages of acute
      and chronic liver diseases of various aetiologies. The place of liver
      transplantation in the treatment of malignant liver disease, in particular
      hepatocellular carcinoma, remains, however, debated: liver transplantation for
      hepatocellular carcinoma achieves 5-year survival similar to that for other
      indications, and 5-year disease-free survival better than that following
      "curative" resection, provided certain criteria are fulfilled (one node max. 5 cm
      in diameter or max. 3 nodes each of max. 3 cm in diameter). This must be weighed
      against the uncertainties of preoperative staging and the shortage of donor
      organs. In contrast, cholangiocarcinoma has a poor prognosis after liver
      transplantation with 3- and 5-year survival rates below 20%. Only small,
      incidental, peripheral, intrahepatic cholangiocarcinomas in patients with primary
      sclerosing cholangitis seem to be an exception to this rule. Liver metastases
      indicate generalised tumour spread, and thus are not an indication for liver
      transplantation. Liver transplantation may be justified for liver metastases of
      neuroendocrine gastrointestinal tumours, provided the primary has been curatively
      resected and there is no extrahepatic spread. Finally, liver-transplanted
      (immunosuppressed) patients are at increased risk to develop malignant tumours.
      This includes in particular epithelial skin tumours, (EBV-associated
      lymphoproliferative diseases and (HHV8-induced) Kaposi's sarcoma.

PMID- 10909725
TI  - [Bleeding from angiodysplasias--endoscopic treatment].

PMID- 10909726
TI  - Ultrasonic effects on electroorganic processes. Part 14. Indirect
      electroreduction of benzyl chlorides with anthracene redox-mediatory system
AB  - Ultrasonic effects were observed in the indirect electroreduction of benzyl
      chlorides with a radical anion mediator electrogenerated from anthracene. Both
      the current efficiency for the toluenes formed and the current density (reaction
      rate) at a working electrode were significantly increased in potential-controlled
      electrolysis under ultrasonic irradiation (20 kHz). These effects are important
      from a practical aspect and are rationalized as being due to mass transport
      promotion caused by ultrasonic cavitation. Although the efficiency could be also
      increased in the direct electroreduction in the absence of the mediator under
      irradiation, the current density was only slightly increased.

PMID- 10909727
TI  - Ultrasonic effects on electroorganic processes. Part 17. Product selectivity
      control in cathodic reduction of acrylonitrile
AB  - Product selectivity for adiponitrile, which was formed as the corresponding
      hydrodimeric product along with propionitrile as the hydromonomeric product in
      the cathodic reduction of acrylonitrile, was significantly increased under
      ultrasonic irradiation with an intensity above the ultrasonic cavitation
      threshold. This ultrasonic effect is rationalized as due to mass transport
      promotion of acrylonitrile molecules to the cathode surface from the bulk
      electrolytic solution by high speed jet streams caused by the cavitation. A
      mechanism for the ultrasonic effect is discussed in detail on the basis of the
      reaction pathway of the hydrodimerization of acrylonitrile.

PMID- 10909728
TI  - Sonochemical formation of nitrate and nitrite in water
AB  - The formation of nitrite and nitrate ions in water under irradiation with 900 kHz
      ultrasound was studied as a function of time, temperature and gas
      (oxygen/nitrogen) composition. The rate decreases as temperature increases, and
      is below the detection limit when there is no O2 gas present. The absolute rate
      of formation of NOx- ions obtained (about 30 x 10(-9) mol min-1 W-1) agrees well
      with previous similar studies. The differences in the NO2-/NO3- ratio found
      between various studies can be satisfactorily explained though a mechanism where
      HNO2 and HNO3 are formed in the gas phase of the imploding cavity, and then
      dissolve in the water and dissociate to ions. The NO2- species is initially
      substantially favoured, as considerably more NO is formed than NO2. Thermodynamic
      calculations indicate that at the 'hot spot' temperature of about 5000 K believed
      to be present, there would very large amounts of NO and OH radicals present, and
      at such high temperatures, thermodynamics would be a good approximation of the
      situation, since the rates of reactions would be very rapid. The reaction needs
      O2 in order to proceed to a significant degree; no NOx- was detected in the
      absence of oxygen gas.

PMID- 10909729
TI  - Sonochemical degradation of chlorophenols in water
AB  - Sonochemical degradation of dilute aqueous solutions of 2-, 3- and 4-chlorophenol
      and pentachlorophenol has been investigated under air or argon atmosphere. The
      degradation follows first-order kinetics in the initial state with rates in the
      range 4.5-6.6 microM min-1 under air and 6.0-7.2 microM min-1 under argon at a
      concentration of 100 microM of chlorophenols. The rate of OH radical formation
      from water is 19.8 microM min-1 under argon and 14.7 microM min-1 under air in
      the same sonolysis conditions. The sonolysis of chlorophenols is effectively
      inhibited, but not completely, by the addition of t-BuOH, which is known to be an
      efficient OH radical scavenger in aqueous sonolysis. This suggests that the main
      degradation of chlorophenols proceeds via reaction with OH radicals; a thermal
      reaction also occurs, although its contribution is small. The addition of
      appropriate amounts of Fe(II) ions accelerates the degradation. This is probably
      due to the regeneration of OH radicals from hydrogen peroxide, which would be
      formed from recombination of OH radicals and which may contribute a little to the
      degradation. The ability to inhibit bacterial multiplication of pentachlorophenol
      decreases with ultrasonic irradiation.

PMID- 10909730
TI  - Evidence against singlet oxygen formation by sonolysis of aqueous oxygen
      saturated solutions of Hematoporphyrin and rose bengal. The mechanism of
      sonodynamic therapy.
AB  - The possible role of singlet oxygen in the mechanism of sonodynamic therapy, the
      synergistic effect of ultrasound and certain sonosensitizers, was investigated.
      We used 4,4'-bis(1-p-carboxyphenyl-3- methyl-5-hydroxyl)-pyrazole (DRD 156), a
      sensitive new reagent which reacts specifically with singlet oxygen (1O2) but not
      with OH radicals, superoxide anion radicals or H2O2, to produce an EPR detectable
      signal. Sonolysis (48 kHz) of 90% D2O oxygen-saturated PBS solutions of
      Hematoporphyrin or Rose Bengal did not lead to the formation of detectable EPR
      signals of the semiquinone radical of DRD156. In contrast, the EPR signal of the
      semiquinone radical of DRD156 was observed during photoirradiation of
      Hematoporphyrin at 505 nm or of Rose Bengal at 544 nm. These results are
      inconsistent with a major role for singlet oxygen formation in the sonolysis of
      aqueous solutions of these compounds. An alternative mechanism for sonodynamic
      therapy involving peroxyl and alkoxyl radicals is discussed.

PMID- 10909731
TI  - Ultrasonic initiation of polystyrene latex synthesis
AB  - Polystyrene latex samples have been synthesised from an oil-in-water (o/w)
      emulsion of the monomer using ultrasonic irradiation as the initiation source. No
      added chemical initiators were used in any of the reactions. The free radicals
      formed from the cavitation process under the action of the ultrasound are
      sufficient to initiate the polymerisation. In the current study, the effects of
      varying the input intensity of the ultrasound were investigated. A marked
      increase in the monomer conversion rate as a function of time was seen as the
      power was increased. Despite this increase in conversion rate, the increasing
      intensity did not affect the resultant latex particle sizes. In all cases, the
      particle diameters at the conclusion of a polymerisation were seen to be in the
      range of 40 to 50 nm. The effects of changing the concentration of surfactant in
      the polymerisation medium and of changing the temperature were also probed.
      Increases in both were seen to lead to an increased rate of conversion at a fixed
      input intensity. Again, the particle diameters were invariant as a function of
      changing conditions. The small particle sizes and high conversion rates are
      thought to be due to a continuous nucleation process that is caused by the
      scavenging of free radicals throughout the polymerisation by freshly formed small
      oil droplets.

PMID- 10909732
TI  - Kinetics of nitrous acid formation in a two-phase tri-n-butylphosphate
      diluent/aqueous nitric acid extraction system under the effect of power
      ultrasound
AB  - The kinetics of nitrous acid formation were investigated in two-phase tri-n
      butylphosphate (TBP)-diluent/HNO3 (1.5-6.0 mol l-1) systems, where diluent is n
      C16H34, n-C12H26, n-C9H20 and i-C8H18, under the effect of power ultrasound at 20
      kHz frequency under Ar atmosphere. The rate of HNO2 sonochemical formation
      decreases with the rise in diluent vapor pressure. The HNO2 formed is distributed
      between the aqueous and organic phases due to its extraction with TBP. The
      kinetics of HNO2 sonochemical formation in the two-phase system exhibits
      induction periods due to NOx (NO + NO2) gas reactions in the HNO3 medium. This
      induction period decreases with increasing HNO3 concentration and ultrasound
      intensity. The HNO2 steady-state concentration was obtained under long-time
      sonication as the result of HNO2 sonochemical decomposition. HNO2 decomposes
      faster under sonication in the aqueous phase than in the organic phase.

PMID- 10909743
TI  - [XVI Brazilian Congress of the Department of Arrhythmia and Clinical
      Electrophysiology. XVI Brazilian Congress of Pediatric Cardiology. VI Brazilian
      Congress of Ergometry. Abstracts].

PMID- 10909744
TI  - 12th World Congress of the International Society for the Study of Hypertension in
      Pregnancy. Paris, France, July 9-13, 2000. Abstracts.

PMID- 10909745
TI  - [GASTRO 2000. National Week of Gastroenterology. Veracruz, Mexico, 4-9 December
      2000. Abstracts].

PMID- 10909746
TI  - [XXI Portuguese Congress of Cardiology. Vilamoura, 9-12 April 2000. Abstracts].

PMID- 10909747
TI  - 6th Annual International Conference of the University Diabetes Outreach Project,
      the Pan American Health Organization, and the Caribbean Food and Nutrition
      Institute: Diabetes and Hypertension. Ocho Rios, Jamaica, March 2-5, 2000.
      Abstracts.

PMID- 10909748
TI  - Messenger RNA transcripts coding for progesterone receptor A and B isoforms are
      expressed in human osteoblast cells.

PMID- 10909749
TI  - Osteoclast differentiation and activity.

PMID- 10909750
TI  - Transcriptional control of osteoblast differentiation.

PMID- 10909751
TI  - Osteogenesis: bone development from primitive progenitors.

PMID- 10909752
TI  - The recombinant expression of bone morphogenetic protein type IA receptor (Alk3)
      in mesenchymal progenitors C3H10T1/2 is sufficient for osteo-/chondrogenic
      development.

PMID- 10909753
TI  - Mechanisms of steroid action on osteoclasts and osteoblasts.

PMID- 10909754
TI  - Functions of nitric oxide in bone.

PMID- 10909755
TI  - Bone markers: overuse and much abuse.

PMID- 10909756
TI  - Therapeutic uses of recombinant complement receptors.

PMID- 10909757
TI  - Definition of the molecular mechanism of action of tissue-selective oestrogen
      receptor modulators.

PMID- 10909758
TI  - Models and responses in depression and aggression.

PMID- 10909759
TI  - Studies on progesterone receptor expression in human osteoblast cells.

PMID- 10909760
TI  - Collagen cross-links levels and bone density in postmenopausal coeliac patients.

PMID- 10909761
TI  - The expression of cartilage oligomeric matrix protein, thrombospondin-1, bone
      sialoprotein and osteopontin in calcified and non-calcified arterial lesions.

PMID- 10909762
TI  - Identification of genes expressed during the osteogenic differentiation of
      vascular pericytes in vitro.

PMID- 10909763
TI  - Serological antigen selection of phage displayed colorectal tumour cDNA
      libraries.

PMID- 10909764
TI  - Glycated IAPP shows a reduced inhibitory action on insulin secretion.

PMID- 10909765
TI  - Generation of a phage display library to determine specificity of proteases.

PMID- 10909766
TI  - Phage-display of antigenic peptides applied to vaccine design.

PMID- 10909767
TI  - Cytokine gene expression during monocyte macrophage maturation and foam cell
      transformation.

PMID- 10909768
TI  - Investigation of methionine metabolism in peripheral blood mononuclear cells of
      Irish hyperhomocysteinemic subjects.

PMID- 10909769
TI  - A latex agglutination assay for the detection of anti-streptokinase antibodies.

PMID- 10909770
TI  - The suppression of lipoprotein lipase expression in J774.2 macrophages by IFN
      gamma and TNF-alpha is mediated at the transcriptional level.

PMID- 10909772
TI  - Characterisation of a prothrombinase activator on the hepatoma derived cell-line,
      PLC/PRF/5.

PMID- 10909771
TI  - Regulation of macrophage lipoprotein lipase expression by lipopolysaccharide.

PMID- 10909773
TI  - Promoter sequence of rat thimet oligopeptidase.

PMID- 10909774
TI  - An antibody-lectin sandwich assay for asialo-LDL levels in atherosclerosis.

PMID- 10909775
TI  - A molecular approach for stroke prevention.

PMID- 10909776
TI  - Stability of type VIII collagen homotrimers: comparison with alpha1(X).

PMID- 10909777
TI  - Secondary structure of a fibrillin-1 eight-cysteine motif.

PMID- 10909778
TI  - Coronary heart disease risk assessment in Kocaeli Region Turkey.

PMID- 10909779
TI  - Validated method for total homocysteine determination.

PMID- 10909780
TI  - The influence of platelet-derived growth factor on lipoprotein lipase gene
      expression.

PMID- 10909781
TI  - Corticosterone influences the NMDA receptor antagonist MK-801 induced
      hyperactivity in the rat.

PMID- 10909782
TI  - The effect of fluid shear stress on osteoblast precursor cells.

PMID- 10909783
TI  - Differential bone morphogenetic protein expression by pluripotent bone marrow
      stromal stem cells.

PMID- 10909784
TI  - Probing the stability of the tertiary structure of glutamate dehydrogenase by
      limited proteolysis.

PMID- 10909785
TI  - Construction and investigation of co-operativity in hybrids of norleucine- and
      glutamate-active subunits of clostridial glutamate dehydrogenase.

PMID- 10909786
TI  - A non-specific soluble dipeptide hydrolase from guinea-pig brain.

PMID- 10909787
TI  - Purification of an extracellular proteinase from Staphylococcus sciuri found on
      the surface of Tilsit cheese.

PMID- 10909788
TI  - NKA, analogs with conformational constraint.

PMID- 10909789
TI  - Gly-(CSNH)-Phe resists hydrolysis by membrane dipeptidase.

PMID- 10909790
TI  - Design, synthesis and properties of conformationally-restricted lipid mimetics.

PMID- 10909791
TI  - Production and characterization of anti-coumarin scFv antibodies.

PMID- 10909792
TI  - NMR studies of the extracellular loop of the beta subunit of the high affinity
      IgE receptor.

PMID- 10909793
TI  - Molecular modelling of the IgE receptor loops-lipid interaction.

PMID- 10909794
TI  - Studies on the aggregation and secondary structure of peptides derived from non-A
      beta component of Alzheimer's disease amyloid.

PMID- 10909795
TI  - Targeting of doxorubicin loaded liposomes to T-cells via the transferrin
      receptor.

PMID- 10909796
TI  - Recombinant anti-polyamine antibodies.

PMID- 10909797
TI  - Production of Fab fragments and Fab-steroid complexes suitable for crystal
      growth.

PMID- 10909798
TI  - Biotinylation of TNF for use in receptor studies.

PMID- 10909799
TI  - Development of a sensitive ELISA for myoglobin detection in the early diagnosis
      of acute myocardial infarction.

PMID- 10909800
TI  - Antibody affinity and the detection limit of solid-phase enzyme immunoassay.

PMID- 10909801
TI  - Superoxide dismutase activity of antibodies purified from the human arteries and
      atherosclerotic lesions.

PMID- 10909802
TI  - A computer model of the LFA-3/CD2 complex.

PMID- 10909803
TI  - Pitfalls of using organic solvents in biological systems.

PMID- 10909804
TI  - Cytokine processing by transformed and non-transformed cell types.

PMID- 10909805
TI  - Isolation of single-chain variable fragment (scFv) antibodies against synthetic
      peptide fragments of human cathepsin S.

PMID- 10909806
TI  - Anti-peptide antibodies to epitopes masked by the carbohydrate moieties in
      transferrin.

PMID- 10909807
TI  - New reagents for the study of perforin synthesis storage and processing.

PMID- 10909808
TI  - Non-lethal effects of perforin on polymorphonuclear leukocytes.

PMID- 10909809
TI  - Development and characterisation of anti-peptide antibodies to rat
      lipopolysaccharide binding protein.

PMID- 10909810
TI  - Modulation of metalloproteinase expression in trophoblast cell lines by
      cytokines.

PMID- 10909811
TI  - Immunoregulatory role of natural autoantibody in health & disease.

PMID- 10909812
TI  - Characterization of immunoglobulins with specificity against non-self-antigens &
      of autoantibody in physiological immune responses (7S/19S).

PMID- 10909813
TI  - Role of autoantibody (7S/19S) in the physiological immune response.

PMID- 10909814
TI  - Binding and signalling properties of a GH-enhancing monoclonal antibody.

PMID- 10909815
TI  - Antioxidant status and DNA damage in patients with insulin-dependent diabetes
      mellitus.

PMID- 10909816
TI  - The role of dietary manipulation in the control of aggression in pigs.

PMID- 10909817
TI  - In vitro toxicological assessment of mixtures of organic solvents of industrial
      importance.

PMID- 10909818
TI  - Enzymatic deglycosylation of casein micelles in bovine milk.

PMID- 10909819
TI  - The effect of a conjugated dienoic derivative of linoleic acid on the in vitro
      growth of MCF-7 and SW480 human cancer cell lines.

PMID- 10909820
TI  - The effect of a conjugated linoleic acid on superoxide dismutase, catalase and
      glutathione peroxidase in oxidatively-challenged liver cells.

PMID- 10909821
TI  - An investigation of thymidine kinase 1 from normal and transformed mammary cell
      lines.

PMID- 10909822
TI  - Hepatic phenylalanine hydroxylase of Clethrionomys glareolus Schreber as a
      bioindicator of pollution.

PMID- 10909823
TI  - Mutations of human medium-chian acyl-CoA dehydrogenase.

PMID- 10909824
TI  - A comparison of some of the methods available for analysing the substrate
      dependence of the exchange of the alpha-protons of amino acids catalysed by
      pyridoxal-phosphate-dependent enzymes.

PMID- 10909825
TI  - Synthesis of benzyloxycarbonylglycylglycinephenylalanine p-nitroanilide and an
      evaluation of its potential as a substrate for alpha-chymotrypsin and subtilisin
      BPN'.

PMID- 10909826
TI  - An attempt to cyanylate the thiol group of bovine serum albumin with 13C-enriched
      cyanide and to observe the thiocyanate carbon by 13C-NMR.

PMID- 10909827
TI  - Quenching of beta-lactoglobulin fluorescence by 2-nitro-5-thiobenzoic acid.

PMID- 10909828
TI  - Effect of the bulk solvent on the pKa values of the oxyanions of serine protease
      derivatives.

PMID- 10909829
TI  - Affinity chromatography of bacterial D-lactate dehydrogenases.

PMID- 10909830
TI  - Purification and properties of psychrophilic dehydrogenases.

PMID- 10909831
TI  - Experimental evidence for the formation of a complex between butyryl coenzyme A
      dehydrogenase and the 'electron transferring flavoprotein', ETF.

PMID- 10909832
TI  - Cysteine-lysine ion pairs in yeast pyruvate carboxylase.

PMID- 10909833
TI  - Alpha1-proteinase inhibitor and alpha1-chymotrypsin inhibitor in Alzheimer's
      disease.

PMID- 10909834
TI  - Report on a longitudinal study of hprt mutant frequency in vivo in a group of
      healthy humans.

PMID- 10909835
TI  - Rapid membrane capture PCR-based method for detection of Listeria species.

PMID- 10909836
TI  - Inappropriate expression of the yeast transcription factor Ace2p affects cell
      growth.

PMID- 10909837
TI  - Mutational spectrum of phenylketonuria in Ireland.

PMID- 10909838
TI  - Stable expression for investigation of possible differential activity of two
      polymorphic forms of the human arginine specific ADP-ribosyltransferase.

PMID- 10909839
TI  - Arginine-specific ADP-ribosyltransferase of human polymorphonuclear neutrophil
      leucocytes: cDNA cloning and identification of a polymorphic site in the coding
      region.

PMID- 10909840
TI  - The formation and secretion of cholesteryl esters in rat hepatocytes are reduced
      by lovastatin and simvastatin.

PMID- 10909841
TI  - Correlation of rat hepatic phenylalanine hydroxylase with concentrations of
      tetrahydrobiopterin and of GTP.

PMID- 10909842
TI  - A coupled enzyme assay for myo-inositol.

PMID- 10909843
TI  - Does urea synthesis play a role in bicarbonate disposal?

PMID- 10909844
TI  - A comparison between the application of the comet assay and an immunochemical DNA
      damage assay on the level of DNA damage within X-ray irradiated human whole
      blood.

PMID- 10909845
TI  - Molecular basis of hereditary pancreatitis.
AB  - Hereditary pancreatitis (HP) is an autosomal dominant disease. Two heterozygous
      missense mutations, R122H (R117H) and N29I (N21I), in the cationic trypsinogen
      gene have been clearly associated with HP. The 'self-destruct' model proposed for
      the R122H mutation is discussed in connection with the existing theory of
      pancreatitis, and the basic biochemistry and physiology of trypsinogen, with
      particular reference to R122 as the primary autolysis site of the cationic
      trypsinogen. Two different genetic mechanisms are identified which cause the
      R122H mutation, and gene conversion is the likely cause of the N29I mutation. A
      unifying model, which highlights an indirect impairment on the R122 autolysis
      site is hypothesised for the N29I mutation. Possible predisposition to
      pancreatitis by additional DNA variants in the gene, such as the A16V signal
      peptide cleavage site mutation and the K23R activation peptide cleavage site
      mutation is suspected, but not proven. Evidence of genetic heterogeneity of HP is
      reviewed and cystic fibrosis transmembrane conductance regulator (CFTR) gene
      mutations detected in HP families are re-evaluated. Finally, large scale
      association studies are expected to clarify the additional variants' role in
      pancreatitis and to identify new HP genes.

PMID- 10909846
TI  - Maternal and paternal lineages in Albania and the genetic structure of Indo
      European populations.
AB  - Mitochondrial DNA HV1 sequences and Y chromosome haplotypes (DYS19 STR and YAP)
      were characterised in an Albanian sample and compared with those of several other
      Indo-European populations from the European continent. No significant difference
      was observed between Albanians and most other Europeans, despite the fact that
      Albanians are clearly different from all other Indo-Europeans linguistically. We
      observe a general lack of genetic structure among Indo-European populations for
      both maternal and paternal polymorphisms, as well as low levels of correlation
      between linguistics and genetics, even though slightly more significant for the Y
      chromosome than for mtDNA. Altogether, our results show that the linguistic
      structure of continental Indo-European populations is not reflected in the
      variability of the mitochondrial and Y chromosome markers. This discrepancy could
      be due to very recent differentiation of Indo-European populations in Europe
      and/or substantial amounts of gene flow among these populations.

PMID- 10909847
TI  - Loss of heterozygosity in renal and hepatic epithelial cystic cells from ADPKD1
      patients.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the commonest
      genetic diseases in man, affecting 1:1000 individuals in the Caucasian
      population. It is caused by mutations in the PKD1 or PKD2 genes. Recently,
      controversial data regarding the mutational mechanism underlying cyst initiation
      have been reported: genetic analyses have shown that second somatic mutations may
      lead to cyst formation (detected as microsatellite loss of heterozygosity, LOH,
      and point mutations), but immunohistochemical studies show strong
      immunoreactivity for polycystin in some cysts. In order to further characterise
      this matter we have analysed 211 cysts from seven different patients for LOH, we
      have detected a 13.3% LOH for PKD1. This loss was specific to PKD1 as no LOH was
      detected when other chromosomal regions were studied. Whenever linkage analysis
      has been possible, it has been proved that the lost allele corresponded to the
      wild-type. Our data supports previous results in the two-hit theory for ADPKD due
      to the large number of cysts studied. ADPKD would occur through a recessive
      cellular mechanism. The probability of cyst development would depend on the
      probability of mutation in the second allele. The different phenotypical
      expression of the same mutation reported in ADPKD could be due to the different
      tendency of inactivation in the second allele in each individual.

PMID- 10909848
TI  - An essential SMN interacting protein (SIP1) is not involved in the phenotypic
      variability of spinal muscular atrophy (SMA).
AB  - The survival motor neuron (SMN) protein and the SMN interacting protein 1 (SIP1)
      are part of a 300 kD protein complex with a crucial role in snRNP biogenesis and
      pre-mRNA splicing. Both proteins are colocalised in nuclear structures called
      gems and in the cytoplasm. Approximately 96% of patients with autosomal recessive
      spinal muscular atrophy (SMA) show mutations in the SMN1 gene, while about 4%
      fail to show any mutation, despite a typical SMA phenotype. Additionally, sibs
      with identical 5q13 homologs and homozygous absence of SMN1 can show variable
      phenotypes which suggest that SMA is modified by other, yet unknown factors.
      Since both genes, SMN1 and SIP1, belong to the same pathway and are part of the
      same protein complex, it is obvious to ask whether mutations within SIP1 are
      responsible for both the phenotypic variability and the appearance of non-SMN
      mutated SMA patients. First, we identified the chromosomal location of SIP1 and
      assigned it to chromosomal region 14q13-q21 by fluorescence in situ
      hybridisation. No SMA related disorder has yet been assigned to this chromosomal
      region. Next, we determined the exon-intron structure of the SIP1 gene which
      encompasses 10 exons and identified five transcription isoforms. We sequenced
      either RT-PCR products or genomic DNA covering the complete coding region from 23
      typical SMA patients who had failed to show any SMN1 mutation. No mutation and no
      polymorphism was found within SIP1. Additionally, we sequenced RT-PCR products or
      genomic fragments of the entire SIP1 coding region from 26 sibs of 11 SMA
      families with identical genotypes (delta7SMN/delta7SMN or delta7SMN/other
      mutation) but different phenotypes and again no mutation was found. Finally, we
      performed quantitative analysis of RT-PCR products from the same 26 sibs. No
      difference in expression level of the five isoforms among phenotypically variable
      sibs was observed. Based on these data, we suggest that neither the phenotypic
      variability nor the 5q-unlinked SMA are caused by mutations within SIP1.

PMID- 10909849
TI  - Identification of novel USH2A mutations: implications for the structure of USH2A
      protein.
AB  - Usher syndrome type II is an autosomal recessive disorder, characterised by
      stable hearing impairment from childhood and progressive retinitis pigmentosa
      from the late teens. Mutations in the USH2A gene, located on 1q41, were recently
      shown to be responsible for Usher syndrome type IIa. We have investigated the
      molecular pathology of Usher type II by screening the USH2A gene for mutations in
      31 unrelated patients from Denmark and Norway. Besides the frequent 2299delG
      mutation, which accounted for 44% of the disease alleles, a heterogeneous
      spectrum of mutations was identified. Sixteen new, putative disease-causing
      mutations were detected, of which 12 were private and four were shared by
      unrelated patients. The disease-causing mutations were scattered throughout the
      gene and included six nonsense and seven missense mutations, two deletions and
      one small insertion. In addition, six non-pathogenic polymorphisms were
      identified. All missense mutations resulted in major amino acid side-chain
      alterations. Four missense mutations affected the N-terminal part of USH2A,
      whereas three missense mutations affected the laminin-type epidermal growth
      factor-like (LE) domain. The structural consequences of the mutations affecting
      the LE domain are discussed in relation to the three-dimensional structure of a
      LE-module of the mouse laminin gamma1 chain.

PMID- 10909850
TI  - Myotonic dystrophy (DM) protein kinase levels in congenital and adult DM
      patients.
AB  - Myotonic dystrophy is caused by a (CTG)n trinucleotide repeat expansion located
      in the 3' untranslated region of the myotonic dystrophy protein kinase gene
      (DMPK). To date, the disease mechanism has proven elusive. The mutation would not
      be expected to affect kinase function and yet the disease is inherited in a
      dominant fashion. Mutant DMPK transcripts have been demonstrated to be retained
      in affected cell nuclei which could reduce DMPK protein levels and cause disease
      by haploinsufficiency. An alternate hypothesis is that the expansion confers a
      toxic gain of function on the transcript. In previous studies, various 52-55 kDa
      proteins have been detected using antisera targeted against DMPK and a decline of
      two of these candidates in disease tissues was reported. Current information now
      suggests that these proteins are not products of the myotonic dystrophy gene. We
      have characterised an antiserum which has been confirmed to recognise authentic
      71 and 80 kDa isoforms of DMPK. Determination of the kinase levels in disease
      tissues with controls for patient age and tissue integrity demonstrates a modest
      overexpression in adult patients. In tissues from severely affected congenital
      patients only a slight decline is seen. This data argues against DMPK
      haploinsufficiency as a disease mechanism.

PMID- 10909851
TI  - Molecular characterisation of 10 Dutch properdin type I deficient families:
      mutation analysis and X-inactivation studies.
AB  - Properdin type I deficiency is characterised by complete absence of extracellular
      properdin, a positive regulator of the alternative pathway of complement
      activation. Properdin deficiency is associated with increased susceptibility to
      severe meningococcal disease. We have identified the genetic defect in 10 Dutch
      families. Six different mutations and one sequence polymorphism in the properdin
      gene were found. All amino acid substitutions were limited to conserved amino
      acids in exons 7 and 8 in contrast to the premature stops that were found in
      other exons. The missense mutations may alter the protein conformation in such a
      way that properdin will not be secreted and therefore catabolised
      intracellularly. The decreased properdin levels found in some healthy females
      carrying one mutated properdin gene were studied for X-inactivation. Most
      carriers with extreme low or high properdin levels showed preferential X
      inactivation for the normal or mutated X chromosome, respectively. We observed
      some exceptions, suggesting additional regulation of properdin excretion apart
      from X-inactivation.

PMID- 10909852
TI  - Effect of the size of the deletion and clinical manifestation in Wolf-Hirschhorn
      syndrome: analysis of 13 patients with a de novo deletion.
AB  - We performed clinical, cytogenetic, and molecular analyses on 13 patients (8
      females and 5 males, aged 6 months to 13 years) with Wolf-Hirschhorn syndrome due
      to de novo deletions of chromosome 4p. All patients presented with the typical
      facial gestalt, microcephaly, and profound mental retardation. Other clinical
      signs were low birth weight (10/13; 77%), postnatal short stature (8/12; 66%),
      muscular hypotonia (12/13; 92%), seizures (11/13; 85%), congenital heart defects
      (4/13; 31%), colobomata of iris (4/12; 33%), genital anomalies (4/13; 31%),
      deafness (3/13; 23%), and renal anomalies (3/13; 23%). The smallest deletion was
      a submicroscopic terminal deletion of nearly 2.5 Mb. The largest was a terminal
      deletion of nearly 30 Mb. Cleft lip/palate, preauricular pits/tags, and
      congenital heart defects were present only in patients with terminal deletions
      larger than 10 Mb. The deviations from mean birth weight, birth length, and
      postnatal head circumference correlated with the size of the deletion.
      Determining the parental origin of the deletion with microsatellite markers, the
      maternal allele was missing in three patients and the paternal allele in eight
      patients. Our observations support the existence of a partial genotype-phenotype
      correlation in Wolf-Hirschhorn syndrome.

PMID- 10909853
TI  - Giant axonal neuropathy locus refinement to a < 590 kb critical interval.
AB  - Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative
      disorder, characterised clinically by the development of chronic distal
      polyneuropathy during childhood, mental retardation, kinky or curly hair,
      skeletal abnormalities and, ultrastructurally, by axons in the central and
      peripheral nervous systems distended by masses of tightly woven neurofilaments.
      We recently localised the GAN locus in 16q24.1 to a 5-cM interval between the
      D16S507 and D16S511 markers by homozygosity mapping in three consanguineous
      Tunisian families. We have now established a contig-based physical map of the
      region comprising YACs and BACs where we have placed four genes, ten ESTs, three
      STSs and two additional microsatellite markers, and where we have identified six
      new SSCP polymorphisms and six new microsatellite markers. Using these markers,
      we have refined the position of our previous flanking recombinants. We also
      identified a shared haplotype between two Tunisian families and a small region of
      homozygosity in a Turkish family with distant consanguinity, both suggesting the
      occurrence of historic recombinations and supporting the conclusions based on the
      phase-known recombinations. Taken together, these results allow us to establish a
      transcription map of the region, and to narrow down the GAN position to a < 590
      kb critical interval, an important step toward the identification of the
      defective gene.

PMID- 10909854
TI  - An autosomal dominant posterior polar cataract locus maps to human chromosome
      20p12-q12.
AB  - We assigned the locus for a previously reported new type of autosomal dominant
      posterior polar cataract (CPP3) to 20p12-q12 by a genome-wide two-point linkage
      analysis with microsatellite markers. CPP3 is characterized by progressive, disc
      shaped, posterior subcapsular opacity. The disease was seen in 10 members of a
      Japanese family and transmitted in an autosomal dominant fashion through four
      generations. We obtained a maximum lod score (Zmax) of 3.61 with a recombination
      fraction (theta) of 0.00 for markers D20S917, D20S885 and D20S874. Haplotype
      analysis gave the disease gene localization at a 15.7-cM interval between D20S851
      and D20S96 loci on chromosome 20p12-q12. Since the BFSP1 that encodes the lens
      specific beaded filament structural protein 1 (filensin) has been mapped around
      the CPP3 region, we performed sequence analysis on its entire coding region.
      However, no base substitution or deletion was detected in the CPP3 patients. The
      mapping of the CPP3 locus to 20p12-q12 not only expands our understanding of the
      genetic heterogeneity in autosomal dominant posterior polar cataracts but also is
      a clue for the positional cloning of the disease gene.

PMID- 10909855
TI  - Extended structural variation of a pentanucleotide repeat in the GSTP1 gene:
      characterisation in a normal population and in thyroid and gastric tumours.
AB  - The promoter region of the human GSTP1 gene contains a polymorphic short tandem
      repeat (STR) locus consisting of pentanucleotide repeat units (ATAAA). In this
      work we report the existence of a total of 26 alleles in a Caucasian population.
      While differences in size (ranging from one to five base pairs) were responsible
      for the major variation, in five size-defined classes, two alternative sequences
      were found. Automatic fragment sizing and sequencing analysis revealed that this
      polymorphism is of a highly complex nature in contrast with previous reports. A
      genetic population study was carried out on a random sample from Portugal showing
      no deviation from Hardy-Weinberg equilibrium. Somatic instability studies were
      also performed on gastric and thyroid tumours using this STR: no instability was
      detected in thyroid tumour tissues when compared with their normal counterpart
      but in gastric tumour tissues microsatellite instability (MSI) was detected in
      9.6% of the cases and loss of heterozygosity (LOH) also in 9.6% of the cases
      studied. The results obtained with GSTP1 in gastric cancer were compared with
      previously reported data on MSI using BAT-26 and several dinucleotide repeat
      markers.

PMID- 10909856
TI  - Pedigree tests of transmission disequilibrium.
AB  - High-resolution mapping is essential for the positional cloning of complex
      disease genes. In outbred populations, linkage disequilibrium is expected to
      extend for short distances and could provide a powerful fine-mapping tool.
      Current family-based association tests use nuclear family members to define
      allelic transmission and controls, but ignore other types of relatives. Here we
      construct a general approach for scoring allelic transmission that accommodates
      families of any size and uses all available genotypic information. Family data
      allows for the construction of an expected genotype for every non-founder, and
      orthogonal deviates from this expectation are a measure of allelic transmission.
      These allelic transmission scores can be used to extend previously described
      tests of linkage disequilibrium for dichotomous or quantitative traits. Some of
      these tests are illustrated, together with a permutation framework for estimating
      exact significance levels. Simulation studies are used to investigate power and
      error rates of the approach. As a practical application, the method is used to
      investigate the relationship between circulating angiotensin-1 converting enzyme
      (ACE) levels and polymorphisms in the ACE gene using previously published data.

PMID- 10909857
TI  - Severe cognitive impairment in DMD: obvious clinical indication for Dp71 isoform
      point mutation screening.
AB  - Duchenne muscular dystrophy is associated with variable degrees of selective
      cognitive defect with lower scores for verbal intelligence and reading abilities.
      A number of findings have shown that rearrangements located in the second part of
      the gene seem to be preferentially associated with cognitive impairment. Several
      dystrophin transcripts are expressed in the brain. The more distal of them, Dp71,
      is predominant. We have carried out a mutational analysis of Dp71 transcript in
      12 DMD patients severely, mildly or not retarded, all without detectable deletion
      or duplication. We have detected five point mutations causing Dp71 premature
      translation termination. All were found among the more severely mentally retarded
      patients of this group (VIQ < 50 and/or no reading acquisition).

PMID- 10909858
TI  - Mutation detection in the aspartoacylase gene in 17 patients with Canavan
      disease: four new mutations in the non-Jewish population.
AB  - Canavan disease is a severe progressive autosomal recessive disorder, which is
      characterised by spongy degeneration of the brain. The disease is caused by
      mutations in the aspartoacylase gene. Two different mutations were reported on
      98% of the alleles of Ashkenazi Jewish patients, in which population the disease
      is highly prevalent. In non-Jewish patients of European origin, one mutation
      (914C > A) is found in 50% of the alleles, the other alleles representing all
      kinds of different mutations. We here describe the results of the mutation
      analysis in 17 European, non-Jewish patients. Ten different mutations were found,
      of which four had not been described before (H21P, A57T, R168H, P181T). A
      deletion of exon4, which until now had only been described once, was revealed in
      all five alleles of Turkish origin tested, indicating that this is a founder
      effect in the Turkish population.

PMID- 10909859
TI  - Current challenges in cancer screening. Part I. Colon cancer screening.

PMID- 10909860
TI  - Current challenges in cancer screening. Part II. Prostate cancer screening.

PMID- 10909861
TI  - Current challenges in cancer screening. Part III. Cervical cancer screening: can
      we do better?

PMID- 10909862
TI  - Natural abundance heteronuclear NMR studies of the T3 mini-loop hairpin in the
      terminal repeat of the adenoassociated virus 2.
AB  - A DNA hairpin containing a T3 loop, as occurs in the terminal repeat of a popular
      gene therapy vector (Adenoassociated Virus 2, AAV2), has been extensively studied
      using homo- and heteronuclear NMR experiments. Almost complete assignment of the
      proton and carbon resonances, including H5'(Pro-S) and H5'(Pro-R) protons, has
      been accomplished at natural abundance. NOESY spectra in H2O and D2O have
      revealed many unusual NOEs, which, when combined with the epsilon, beta, gamma,
      and chi torsion angles determined from heteronuclear 1H-13C, 1H-31P, and 13C-31P
      coupling constants, have allowed for a more detailed picture of the T3 mini-loop
      hairpin. The three loop thymidines are all unpaired, yet are highly structured
      when bracketed by a 5'-GC...GC-3' stem sequence. The structure determined in this
      manuscript is considerably different from several other structures reported so
      far. Contrary to an RNA oligomer with a central U3 sequence that has the tendency
      to form a duplex with three U*U mismatches, the d(GAAGC-TTT-GCTTC) sequence
      exists mostly as a hairpin under millimolar NMR conditions. Since T3 triloop was
      found to be an essential element for the site-specific non-homologous integration
      of the AAV2 virus, and modification of the T3 loop residue abolishes such
      capability, the structure we report here may be of biological significance.

PMID- 10909863
TI  - Accuracy of bound peptide structures determined by exchange transferred nuclear
      Overhauser data: a simulation study.
AB  - The exchange-transferred NOE method to determine the three-dimensional structure
      of peptides bound to proteins, or other macromolecular systems, is becoming
      increasingly important in drug design efforts and for large or multicomponent
      assemblies, such as membrane receptors, where structural analysis of the full
      system is intractable. The exchange-transferred nuclear Overhauser effect
      spectroscopy (etNOESY) method allows the determination of the bound-state
      conformation of the peptide from the intra-molecular NOE interactions between
      ligand protons. Because only ligand-ligand NOEs are generally observable, the
      etNOESY method is restricted to fewer NOEs per residue than direct protein
      structure determination. In addition, the averaging of relaxation rates between
      free and bound states affects the measured cross-peak intensities, and possibly
      the accuracy of distance estimates. Accordingly, the study reported here was
      conducted to examine the conditions required to define a reliable structure. The
      program CORONA was used to simulate etNOE data using a rate-matrix including
      magnetic relaxation and exchange rates for two peptide-protein complexes derived
      from the reference complex of cAMP-dependent protein kinase ligated with a 24
      residue inhibitor peptide. The results indicate that reasonably accurate peptide
      structures can be determined with relatively few NOE interactions when the
      interactions occur between non-neighboring residues. The reliability of the
      structural result is suggested from the pattern of NOE interactions. A structure
      with an accuracy of approximately 1.3 A rms difference for the main-chain atoms
      can be obtained when etNOE interactions between non-neighboring residues occur
      over the length of the peptide. The global precision is higher (approximately 0.9
      A rms difference) but is not correlated to global accuracy. A local definition of
      precision along the backbone appears to be a good indicator of the local
      accuracy.

PMID- 10909864
TI  - Deuterium isotope effects on the central carbon metabolism of Escherichia coli
      cells grown on a D2O-containing minimal medium.
AB  - Isotope effects on the central carbon metabolism due to the addition of variable
      amounts of D2O (0 to 70%) were investigated with biosynthetically directed
      fractional 13C-labeling for Escherichia coli BL21(DE3) cells during exponential
      growth on a M9 minimal medium containing a mixture of 70% unlabeled and 30%
      uniformly 13C-labeled glucose as the sole carbon source. The resulting 13C
      labeling patterns in the amino acids were analysed by two-dimensional [13C,1H]
      correlation spectroscopy. With the aforementioned growth conditions, higher D2O
      contents resulted in an increase of the anaplerotic supply of the tricarboxylic
      acid cycle via carboxylation of phosphoenolpyruvate when compared to the influx
      of acetyl-CoA. Furthermore, the addition of D2O affected the C1 metabolic
      pathways that involve Ser and Gly. Otherwise the E. coli cells showed identical
      topologies of the active biosynthetic pathways in H2O and at elevated D2O
      contents, and the metabolic flux ratios characterizing glycolysis and the pentose
      phosphate pathway were not measurably affected by the addition of D2O. Cells that
      had been adapted for growth in D2O exhibited the same response to the presence of
      D2O in the nutrient medium as non-adapted cells. Implications of these data for
      the preparation of recombinant deuterated proteins for NMR studies are discussed.

PMID- 10909865
TI  - A set of HNCO-based experiments for measurement of residual dipolar couplings in
      15N, 13C, (2H)-labeled proteins.
AB  - Several HNCO-based three-dimensional experiments are described for the
      measurement of 13C'(i - 1)-13Calpha(i - 1), 5N(i)-13C'(i - 1), 15N(i)
      13Calpha(i), 15N(i)-13Calpha(i - 1), 1H(N)(i)-13Calpha(i), 1H(N)(i)-13Calpha(i -
      1), and 13Calpha(i - 1)-13Cbeta(i - 1) scalar and dipolar couplings in 15N, 13C,
      (2H)-labelled protein samples. These pulse sequences produce spin-state edited
      spectra superficially resembling an HNCO correlation spectrum, allowing accurate
      and simple measurement of couplings without introducing additional spectral
      crowding. Scalar and dipolar couplings are measured with good sensitivity from
      relatively large proteins, as demonstrated with three proteins: cardiac Troponin
      C, calerythrin and ubiquitin. Measurement of several dipolar couplings between
      spin-1/2 nuclei using spin-state selective 3D HNCO spectra provides a wealth of
      structural information.

PMID- 10909866
TI  - Sensitivity enhanced NMR spectroscopy by quenching scalar coupling mediated
      relaxation: application to the direct observation of hydrogen bonds in 13C/15N
      labeled proteins.
AB  - In this paper, we demonstrate that the sensitivity of triple-resonance NMR
      experiments can be enhanced significantly through quenching scalar coupling
      mediated relaxation by using composite-pulse decoupling (CPD) or.an adiabatic
      decoupling sequence on aliphatic, in particular alpha-carbons in 13C/15N-labeled
      proteins. The CPD-HNCO experiment renders 50% sensitivity enhancement over the
      conventional CT-HNCO experiment performed on a 12 kDa FK506 binding protein, when
      a total of 266 ms of amide nitrogen-carbonyl carbon defocusing and refocusing
      periods is employed. This is a typical time period for the direct detection of
      hydrogen bonds in proteins via trans-hydrogen bond 3hJ(NC') couplings. The
      experimental data fit theoretical analysis well. The significant enhancement in
      sensitivity makes the experiment more applicable to larger-sized proteins without
      resorting to perdeuteration.

PMID- 10909868
TI  - Detection of very weak side chain-main chain hydrogen bonding interactions in
      medium-size 13C/15N-labeled proteins by sensitivity-enhanced NMR spectroscopy.
AB  - We describe the direct observation of very weak side chain-main chain hydrogen
      bonding interactions in medium-size 13C/15N-labeled proteins with sensitivity
      enhanced NMR spectroscopy. Specifically, the remote correlation. between the
      hydrogen acceptor side chain carboxylate carbon 13CO2delta of glutamate 54 and
      the hydrogen donor backbone amide 15N of methionine 49 in a 12 kDa protein, human
      FKBP12, is detected via the trans-hydrogen bond 3hJ(NCO2delta) coupling by
      employing a novel sensitivity-enhanced HNCO-type experiment, CPD-HNCO. The
      3hJ(NCO2delta) coupling constant appears to be even smaller than the average
      value of backbone 3hJ(NC') couplings, consistent with more extensive local
      dynamics in protein side chains.

PMID- 10909869
TI  - Complete 1H and non-carbonylic 13C assignments of native hen egg-white lysozyme.

PMID- 10909867
TI  - The cisproline(i - 1)-aromatic(i) interaction: folding of the Ala-cisPro-Tyr
      peptide characterized by NMR and theoretical approaches.
AB  - Cisproline(i - 1)-aromatic(i) interactions have been detected in several short
      peptides in aqueous solution by analysis of anomalous chemical shifts measured by
      1H-NMR spectroscopy. This formation of local structure is of importance for
      protein folding and binding properties. To obtain an atomic-detail
      characterisation of the cisproline(i - 1)-aromatic(i) interaction in terms of
      structure, energetics and dynamics, we studied the minimal peptide unit, blocked
      Ala-cisPro-Tyr, using computational and experimental techniques. Structural
      database analyses and a systematic search revealed two groups of conformations
      displaying a cisproline(i - 1)-aromatic(i) interaction. These conformations were
      taken as seeds for molecular dynamics simulations in explicit solvent at 278 K.
      During a total of 33.6 ns of simulation, all the 'folded' conformations and some
      'unfolded' states were sampled. 1H- and 13C-chemical shifts and 3J-coupling
      constants were measured for the Ala-Pro-Tyr peptide. Excellent agreement was
      found between all the measured and computed NMR properties, showing the good
      quality of the force field. We find that under the experimental and simulation
      conditions, the Ala-cisPro-Tyr peptide is folded 90% of the time and displays two
      types of folded conformation which we denote 'a' and 'b'. The type a
      conformations are twice as populated as the type b conformations. The former have
      the tyrosine ring interacting with the alanine alpha proton and are enthalpically
      stabilised. The latter have the aromatic ring interacting with the proline side
      chain and are entropically stabilised. The combined and complementary use of
      computational and experimental techniques permitted derivation of a detailed
      scenario of the 'folding' of this peptide.

PMID- 10909870
TI  - 1H, 13C and 15N resonance assignments for a truncated and inhibited catalytic
      domain of matrix metalloproteinase-2.

PMID- 10909871
TI  - Sequence-specific 1H, 13C, and 15N assignment of the human melanoma inhibitory
      activity (MIA) protein.

PMID- 10909872
TI  - Sequence-specific 1H, 15N and 13C resonance assignments of the EEA1 FYVE domain.

PMID- 10909873
TI  - Sequence-specific 1H, 15N, and 13C assignment of the N-terminal domain of the
      human oncoprotein MDM2 that binds to p53.

PMID- 10909874
TI  - The cognitive impact of past behavior: influences on beliefs, attitudes, and
      future behavioral decisions.
AB  - To study the processes by which past behavior influences future behavior,
      participants were led to believe that without being aware of it, they had
      expressed either support for or opposition to the institution of comprehensive
      exams. Judgment and response time data suggested that participants' perceptions
      of their past behavior often influenced their decisions to repeat the behavior.
      This influence was partly the result of cognitive activity that influenced
      participants' cognitions about specific behavioral consequences and the attitude
      they based on these cognitions. More generally, however, feedback about past
      behavior had a direct effect on participants' attitudes and ultimate behavioral
      decisions that was independent of the outcome-specific cognitions. Results are
      discussed in terms of their implications for biased scanning of memory,
      dissonance reduction, self-perception, and the use of behavior as a heuristic.

PMID- 10909875
TI  - The "relative self": informational and judgmental consequences of comparative
      self-evaluation.
AB  - Results of 5 studies demonstrated that self-evaluative comparisons have 2
      distinct informational consequences with opposing judgmental effects: They
      selectively increase the accessibility of standard-consistent self-knowledge and
      provide an evaluative reference point. The first informational consequence
      produces assimilation in self-evaluative judgments, whereas the latter yields
      contrast. Using a lexical decision task, Study 1 demonstrated that a social
      comparison selectively increases the accessibility of standard-consistent self
      knowledge. Study 2 showed that this effect also holds for comparisons with
      objective standards. Studies 3 and 4 revealed that the same comparison may lead
      to assimilation on objective and contrast on subjective self-judgments. Finally,
      Study 5 demonstrated that assimilation results for comparisons with relevant and
      irrelevant standards, whereas contrast occurs only for relevant standards.

PMID- 10909876
TI  - Approach and avoidance: the influence of proprioceptive and exteroceptive cues on
      encoding of affective information.
AB  - In 3 experiments, the authors tested the assumption that perceived movements
      toward a person trigger the approach system and thereby facilitate the processing
      of positive affective concepts, whereas perceived movements away from a person
      trigger the avoidance system and thereby facilitate the processing of negative
      affective concepts. In the 1st study, participants categorized positive words
      more quickly than negative words while flexing the arm and negative words more
      quickly than positive words while extending the arm. The 2nd study revealed that
      positive words were categorized more rapidly than negative words if viewers had
      the impression that they were moving toward the computer screen, whereas negative
      words were categorized faster if viewers had the impression that they were moving
      away from the screen. These findings were replicated in Experiment 3 using a
      lexical decision task instead of an adjective evaluation task.

PMID- 10909877
TI  - Is acculturation unidimensional or bidimensional? A head-to-head comparison in
      the prediction of personality, self-identity, and adjustment.
AB  - The unidimensional model of acculturation posits that heritage and mainstream
      culture identifications have a strong inverse relation, whereas the bidimensional
      model posits that the 2 identifications are independent. The authors compared
      these models in 3 samples of ethnic Chinese (ns = 164, 150, and 204), 1 sample of
      non-Chinese East Asians (n = 70), and one diverse group of acculturating
      individuals (n = 140). Although the unidimensional measure showed a coherent
      pattern of external correlates, the bidimensional measure revealed independent
      dimensions corresponding to heritage and mainstream culture identification. These
      dimensions displayed patterns of noninverse correlations with personality, self
      identity, and psychosocial adjustment. The authors conclude that the
      bidimensional model is a more valid and useful operationalization of
      acculturation.

PMID- 10909878
TI  - Egocentric empathy gaps between owners and buyers: misperceptions of the
      endowment effect.
AB  - In 5 studies, the authors examined people's perceptions of the endowment effect,
      or the tendency to value an object more once one owns it. In the 1st 2 studies,
      the authors documented egocentric empathy gaps between owners and buyers
      regarding the endowment effect: Both owners and buyers overestimated the
      similarity between their own valuation of a commodity and the valuation of people
      in the other role. The next 2 studies showed that these empathy gaps may lead to
      reduced earnings in a market setting. The final study showed that egocentric
      empathy gaps stem partly from people's misprediction of what their own valuation
      would be if they were in the other role.

PMID- 10909879
TI  - Intergroup discrimination in the minimal group paradigm: categorization,
      reciprocation, or fear?
AB  - H. Tajfel's (1970) minimal group paradigm (MGP) research suggests that social
      categorization is a sufficient antecedent of ingroup-favoring discrimination. Two
      experiments examined whether discrimination in the MGP arises from categorization
      or processes of outcome dependence, that is, ingroup reciprocity and outgroup
      fear. Experiment 1 unconfounded categorization from outcome dependence.
      Categorized men discriminated only when dependent on others. Categorized women
      discriminated regardless of the structure of dependence. Experiment 2 examined
      dependence on the ingroup versus the outgroup as the locus of male-initiated
      discrimination. Consistently with an ingroup reciprocity effect, men
      discriminated when dependent on ingroup, but not outgroup, members. Sex
      differences are discussed in regard to women's heightened ingroup dependence
      produced by biological or environmental constraints.

PMID- 10909880
TI  - The personal-group discrepancy: Is there a common information basis for personal
      and group judgment?
AB  - In contrast to motivational accounts of the personal-group discrepancy, results
      from this article suggest that the discrepancy is explained by aggregating
      different sets of comparison outcomes for either personal or group ratings.
      Results from a longitudinal study with East German (the minority group) and West
      German (the majority group) samples confirm the personal-group discrepancy and
      support our approach. First, social comparisons influenced evaluations of
      economic situation at both group and personal levels. Second, ratings of group
      versus personal economic situation were based on different sets of comparisons.
      Third, the mean structure of both sets of comparison outcomes mirrored the
      personal-group discrepancy. Fourth, an interaction between personal-group
      discrepancy and group status supported the authors' suggestions-concerning the
      direction of the discrepancy.

PMID- 10909881
TI  - Handshaking, gender, personality, and first impressions.
AB  - Although people's handshakes are thought to reflect their personality and
      influence our first impressions of them, these relations have seldom been
      formally investigated. One hundred twelve participants had their hand shaken
      twice by 4 trained coders (2 men and 2 women) and completed 4 personality
      measures. The participants' handshakes were stable and consistent across time and
      coders. There were also gender differences on most of the handshaking
      characteristics. A firm handshake was related positively to extraversion and
      emotional expressiveness and negatively to shyness and neuroticism; it was also
      positively related to openness to experience, but only for women. Finally,
      handshake characteristics were related to the impressions of the participants
      formed by the coders. These results demonstrate that personality traits, assessed
      through self-report, can predict specific behaviors assessed by trained
      observers. The pattern of relations among openness, gender, handshaking, and
      first impressions suggests that a firm handshake may be an effective form of self
      promotion for women.

PMID- 10909882
TI  - The body as a source of self-esteem: the effect of mortality salience on
      identification with one's body, interest in sex, and appearance monitoring.
AB  - The present research investigated the role of the physical body as a source of
      self-esteem and tested the hypothesis derived from terror management theory that
      reminding people of their mortality increases self-esteem striving in the form of
      identification with one's body, interest in sex, and appearance monitoring. The
      results revealed that individuals high in body esteem responded to mortality
      salience manipulations with increased identification with their physical bodies
      in Study 1 and with increased interest in sex in Study 2. Study 3 showed that
      reminders of death led to decreased appearance monitoring among appearance
      oriented participants who were low in body esteem. These findings provide insight
      into why people often go to extreme lengths to meet cultural standards for the
      body and its appearance.

PMID- 10909883
TI  - Coping and physical health during caregiving: the roles of positive and negative
      affect.
AB  - The associations among coping, mood, and health variables were examined
      prospectively over 2 years in 86 HIV positive (HIV+) and 167 HIV negative (HIV-)
      gay men undergoing the stress of AIDS-related caregiving. Path models suggested
      that including both positive and negative mood and the men's associated coping
      strategies increases understanding of why some people suffer adverse health
      effects during times of stress. Among the HIV- caregivers, higher levels of
      social coping predicted increases in positive affect, which in turn resulted in
      lower levels of physical symptoms. In contrast, higher levels of cognitive
      avoidance predicted increases in negative affect, which in turn resulted in
      higher levels of physical symptoms. Self-injurious forms of avoidance coping
      predicted higher levels of physical symptoms independent of mood among the HIV+
      caregivers.

PMID- 10909884
TI  - Attitude toward women's societal roles moderates the effect of gender cues on
      target individuation.
AB  - In 4 studies, participants read trait descriptions and formed impressions of 2
      male and 2 female targets. They then attempted to recall which traits had
      described each target. As predicted, participants with a "progressive" attitude
      toward women's rights and roles (J. T. Spence, R. L. Helmreich, & J. Stapp, 1973)
      made fewer within-group recall errors for female targets than for male targets,
      indicating greater individuation of the female targets, whereas participants with
      a "traditional" attitude made fewer errors for male targets. The findings of a
      5th study suggested that progressive participants were motivated to individuate
      women by their belief that it is important to improve the status of women and
      other groups low in power and by their identification with women and feminism.
      Traditional participants' greater individuation of men was believed to stem from
      their perception of men's higher status (as confirmed by pretests) and their
      acceptance of the status quo.

PMID- 10909885
TI  - Chemokines as mediators of diseases related to surgical conditions.
AB  - Chemokines are important mediators of inflammation. Animal studies suggest that
      inhibition of chemokine action results in a decrease in inflammation. Novel anti
      inflammatory agents directed against chemokines are now available. Surgeons are
      uniquely positioned to treat multiple chemokine-mediated diseases. In this
      article, we review the biology and nomenclature of chemokines as well as their
      role in neutrophil migration. Further, the potential role of chemokines in
      various diseases related to surgical conditions, including adult respiratory
      distress syndrome, atherosclerosis, inflammatory bowel disease, and solid organ
      rejection, is reviewed. Finally, the idea that chemokines could be targets for
      novel therapeutic agents is discussed.

PMID- 10909886
TI  - Time-pattern of lactate and lactate to pyruvate ratio in the first 24 hours of
      intensive care emergency admissions.
AB  - Blood lactate elevation in critically ill patients commonly is taken as a sign of
      impaired tissue perfusion. Simultaneous elevation of lactate to pyruvate ratio
      (L/P ratio) may be helpful in discriminating between different mechanisms of
      hyperlactatemia and thus in determining the relevance of the finding. We studied
      prospectively the prevalence and the time pattern of hyperlactatemia and
      simultaneous L/P ratio elevation in 98 consecutive emergency admission patients
      in a 23-bed surgical-medical University Hospital intensive care unit. Blood
      lactate, L/P ratio, and blood gases were measured at 2-h intervals during the
      initial 24 h of intensive care unit admission. Hyperlactatemia (blood lactate
      over 2 mmol/L) was found in 48 (49%) patients, and the median peak value of the
      non-survivors was higher than that of the survivors [5.3 (interquartile range 1.9
      7.5) vs. 1.9 (1.3-2.9) mmol/L, respectively, p = 0.003]. Hyperlactatemia at
      admission (n = 31) was associated with a higher hospital mortality than
      hyperlactatemia developing later (n = 17) (29.0% vs. 5.9%, P = 0.003). Sustained
      admission hyperlactatemia (>6 h) was associated with higher mortality than short
      lasting hyperlactatemia (36.8% vs. 0%, P = 0.008). Simultaneously elevated L/P
      ratio (L/P ratio > 18; n = 16) was associated with higher mortality than
      hyperlactatemia with normal L/P ratio (n = 32; 37.5% vs. 12.5%, respectively, P =
      0.03) and was found mainly in patients who had severe circulatory failure. The
      hyperlactatemia of patients with sepsis was not associated with L/P ratio
      elevation. We conclude that hyperlactatemia is common in emergency admission
      patients. Hyperlactatemia with L/P ratio elevation and lactic acidosis is likely
      to be associated with inadequate tissue perfusion. Hyperlactatemia persisting
      more than 6 h and simultaneous elevation of L/P ratio are associated with
      increased mortality.

PMID- 10909887
TI  - Gastric-arterial PCO2 gradient does not reflect systemic and splanchnic
      hemodynamics or oxygen transport after cardiac surgery.
AB  - Gastric mucosal-arterial PCO2 gradient (P(g-a)CO2) is used to assess splanchnic
      perfusion and oxygenation. We evaluated whether P(g-a)CO2 reflects whole body (Q)
      and splanchnic (Qsp) blood flow, oxygen delivery (DO2) and consumption (VO2)
      after coronary artery by pass graft (CABG) operation. Thirty patients received
      dobutamine or dopexamine to increase cardiac index, 15 patients enalapril or
      sodium nitroprusside to lower blood pressure, and 30 patients were controls. We
      measured Q, Qsp (hepatic vein catheter and indocyanine green), and gastric
      mucosal PCO2 (nasogastric tonometer) before and after interventions. Multiple
      linear regression model showed that none of the changes in Q, Qsp, and splanchnic
      or systemic DO2 and VO2 significantly explained changes in P(g-a)CO2 (deltaP(g
      a)CO2). All independent variables together explained only 7% of deltaP(g-a)CO2.
      Increased splanchnic blood flow (0.65 +/- .19 vs. 0.94 +/- .31 L/min/m2, P <
      0.001) and increased splanchnic DO2 (101 +/- 28 vs. 143 +/- 42 mL/min/m2, P <
      0.001) during catecholamine infusions were associated with increased P(g-a)CO2 (8
      +/- 8 vs. 11 +/- 7 mmHg, P = 0.003). P(g-a)CO2 does not reflect whole body or
      splanchnic blood flow, DO2 or VO2 after CABG operations. The physiology of P(g
      a)CO2 is complex and therefore it is difficult for clinicians to interpret
      changes in gastric mucosal-arterial PCO2 gradient in individual patients after
      cardiac surgery.

PMID- 10909888
TI  - Does the timing of hypertonic saline resuscitation affect its potential to
      prevent lung damage?
AB  - Hypertonic saline (HS) resuscitation has been reported to prevent lung damage by
      suppressing neutrophil activation in animal models. Data on the effectiveness of
      HS to prevent organ damage in the clinical setting are inconsistent. We
      investigated whether the timing of HS administration relative to neutrophil
      activation could affect its potential to block neutrophil responses. Different
      likely clinical circumstances were simulated in vitro by exposing human
      neutrophils to HS at different time points before and after activation with N
      formyl-methionyl-leucyl-phenylalanine (fMLP). The in vivo effect of using HS as a
      secondary resuscitation fluid was determined with a mouse model of hemorrhage.
      BALB/c mice were hemorrhaged (40 +/- 5 mmHg) for 1 h and partially resuscitated
      with HS or Lactated Ringer's (LR) 20 min before completing resuscitation with LR
      or HS, respectively. Neutrophil activation parameters were determined 2 h after
      complete resuscitation and lung damage was assessed after 24 h. The length of
      exposure to physiologically relevant HS levels (20 mM) determined the suppressive
      effect on in vitro neutrophil superoxide formation. HS treatment caused a
      transient state of suppression during which neutrophil activation was suppressed;
      however, HS was unable to suppress cells that were stimulated with fMLP before HS
      was added. Accordingly, in vivo lung damage was greater in animals that received
      HS after they had been partially resuscitated with LR compared to mice that
      received HS before LR (P < 0.05). We conclude that timing of exposure to HS
      affects neutrophil responses in vitro and may reduce the potential of HS
      resuscitation to prevent lung injury in vivo.

PMID- 10909889
TI  - Hypertonic/hyperoncotic resuscitation after intestinal superior mesenteric artery
      occlusion: early effects on circulation and intestinal reperfusion.
AB  - The objective of the study was to determine the early effects of
      hypertonic/hyperoncotic starch resuscitation after 2 h occlusion of the superior
      mesenteric artery (SMA) in comparison to animals reperfused without treatment and
      isotonic resuscitation. SMA was clamped (18 pigs, 19-23 kg) for 2 h followed by a
      2-h reperfusion period, which was initiated with isotonic (ISO) (35 mL/kg 0.9%
      NaCl and 5 mL/kg 10% hydroxyethyl starch within 30 min) or
      hypertonic/hyperoncotic resuscitation (HHES) (7.5% NaCl/10% hydroxyethyl starch
      within 5 min). Cardiac output (CO), mean arterial blood pressure (MAP), serum
      lactate, antimesenteric serosal Laser-Doppler values (LD), and intramural pHi
      (tonometry) were measured. Without resuscitation at the onset of reperfusion MAP
      (70 +/- 3 mmHg) decreased to 40 +/- 3 mmHg and CO to 31% of baseline values after
      30 min. Serum lactate increased to 5.1 +/- 1.6 mmol/L without improvement. The
      decrease of CO was attenuated only during the initial 30 min of reperfusion in
      the ISO group, but significantly better counteracted by hypertonic/hyperoncotic
      resuscitation. Without treatment, LD flow of the ileum (baseline 23-27 LD units)
      recovered but intramural pH (pHi) remained significantly decreased (7.26 +/-
      0.05). With isotonic resuscitation LD values (21.8 +/- 2.1 LD units) and
      intramural pHi (7.09 +/- 0.14) decreased even more (P < 0.05) whereas the HHES
      group showed a significant hyperemic reaction and a normalization of the
      intramural pHi and serum lactate within 30 min. Hypertonic/hyperoncotic
      resuscitation significantly improves MAP and CO during reperfusion shock and
      induces an immediate hyperemic reperfusion reaction of the intestinal
      microcirculation. Adequate isotonic fluid replacement in order to restore the
      postischemic plasma volume loss may cause a pronounced deterioration of
      intestinal perfusion.

PMID- 10909891
TI  - Tissue oxygenation and hemodynamic response to NO synthase inhibition in septic
      shock.
AB  - The objective of the study was to evaluate the tissue oxygenation and hemodynamic
      effects of NOS inhibition in clinical severe septic shock. Eight patients with
      septic shock refractory to volume loading and high level of adrenergic support
      were prospectively enrolled in the study. Increasing doses of NOS inhibitors
      [N(G)-nitro-L-arginine-methyl ester (L-NAME) or N(G)-monomethyl-L-arginine (L
      NMMA)] were administered as i.v. bolus until a peak effect = 10 mmHg on mean
      blood pressure was obtained or until side effects occurred. If deemed clinically
      appropriate, a continuous infusion of L-NAME was instituted and adrenergic
      support weaning attempted. The bolus administration of NOS inhibitors transiently
      increased mean blood pressure by 10 mm Hg in all patients. Seven out of eight
      patients received an L-NAME infusion, associated over 24 h with a progressive
      decline in cardiac index (P < 0.001) and an increase in systemic vascular
      resistance (P < 0.01). Partial or total adrenergic support weaning was rapidly
      possible in 6/8 patients. Oxygen transport decreased (P < 0.001), but oxygen
      consumption remained unchanged in those patients in whom it could be measured by
      indirect calorimetry (5/8). Blood lactate and the difference between tonometric
      gastric and arterial PCO2 remained unchanged. There were 4/8 ICU survivors. We
      conclude that nitric oxide synthase inhibition in severe septic shock was
      followed with a progressive correction of the vasoplegic hemodynamic disturbances
      with finally normalization of cardiac output and systemic vascular resistances
      without any demonstrable deterioration in tissue oxygenation.

PMID- 10909890
TI  - Plasma activation during splanchnic arterial occlusion shock.
AB  - During circulatory shock, activating factors for cells in the microcirculation
      can be detected in plasma. But the source of such activators has remained
      uncertain. We have demonstrated recently that homogenates derived from the
      pancreas but not other peritoneal organs activate naive leukocytes. Production of
      such activating factors can be blocked by a serine protease inhibitor. Thus,
      factors generated by pancreatic proteases may possibly produce cellular
      activation in vivo. Rats were subjected to 90 min of superior mesenteric and
      celiac artery occlusion followed by reperfusion (SAO shock). In addition, rats
      were subjected to SAO shock for 120 min, after a 60-min pretreatment prior to
      occlusion with either saline or the serine protease inhibitor Futhan (nafamostat
      mesilate, 3.3 mg/kg b.w.). A sham SAO protocol was carried out as a control.
      Cellular activation was tested by neutrophil pseudopod formation and NBT
      reduction. Plasma from SAO-shocked animals but not sham shock rats exhibited a
      significant increase (P < 0.001) in the activation of naive leukocytes. Futhan
      treated animals subjected to SAO shock exhibited a significantly higher post
      reperfusion blood pressure than non-treated animals (P < 0.005 for all time
      points greater than 120 minutes), as well as significantly greater survival (P <
      0.001). Neutrophil pseudopod formation and plasma peroxide production, an
      additional index of cellular activation, were significantly lower in Futhan
      treated SAO shock plasma (P < 0.05) than levels in non-treated SAO shock animals.
      These results demonstrate that activating factors for leukocyte are released in
      SAO shock and can be mitigated by pretreatment with the serine protease inhibitor
      Futhan. Proteolytically derived plasma factors released during SAO shock may
      contribute to leukocyte activation and ensuing organ dysfunction.

PMID- 10909892
TI  - Distinct effects of systemic infusion of G-CSF vs. IL-6 on lung and liver
      inflammation and injury in hemorrhagic shock.
AB  - Production of pro-inflammatory cytokines, such as granulocyte colony-stimulating
      factor (G-CSF) and interleukin-6 (IL-6) occurs at multiple tissue sites in
      hemorrhagic shock (HS), resulting in elevated circulating plasma levels. The
      current study was designed to test the hypothesis that circulating G-CSF and IL-6
      contribute to polymorphonuclear neutrophilic granulocyte (PMN)-mediated
      inflammation and organ injury in HS. Sprague-Dawley rats were subjected to
      decompensated HS (mean arterial blood pressure = 40 mm Hg for 2.5 h), followed by
      resuscitation with lactated Ringer's solution with or without G-CSF (3 microg/kg)
      or IL-6 (3 microg/kg). Animals were killed 4 h after resuscitation, and their
      lungs and livers were assessed quantitatively for PMN infiltration, organ injury,
      and activation of NF-kappaB and signal transducer and activator or transcription
      (STAT) 3. Infusion of G-CSF during resuscitation increased PMN infiltration into
      the lungs by 2.4-fold (P < 0.01) compared with animals resuscitated with lactated
      Ringer's solution alone. Increased PMN infiltration was accompanied by
      interstitial edema and pneumocyte swelling, resulting in a 42% increase in lung
      alveolar wall cross-sectional surface area (P < 0.01) and a 3.7-fold increase in
      Stat3 activity (P < 0.01). G-CSF infusion did not affect PMN infiltration into
      the liver and was accompanied by a 68% decrease in focal hepatocellular necrosis
      (P < 0.01). Infusion of IL-6, in contrast, dramatically decreased inflammation
      and injury in both the lung and liver; the anti-inflammatory effects of IL-6 may
      be mediated, in part, by down-modulation of nuclear factor (NF)-kappaB activity.
      Thus, circulating G-CSF and IL-6 have opposing effects on PMN recruitment and
      injury in the lung in HS while both protect against hepatic necrosis. The
      beneficial effect of these cytokines on liver injury in HS appears to be
      independent of PMN recruitment.

PMID- 10909893
TI  - Effect of LFA-1beta antibody on leukocyte adherence in response to hemorrhagic
      shock in rats.
AB  - The activation and adherence of leukocytes to the venular endothelium are
      critical steps in the pathogenesis of generalized microvascular injury following
      hemorrhagic shock. Previous studies have shown that the integrins CD11/CD18 play
      a significant role in this interaction. The purpose of this study is to examine
      the efficacy of anti-LFA-1beta, an antibody to CD11a/CD18, in attenuating
      leukocyte adherence before, during, and after hemorrhagic shock. Following a
      control period, blood was withdrawn to reduce the mean arterial pressure to 40 mm
      Hg for 30 min in urethane-anesthetized rats. Mesenteric venules in a
      transilluminated segment of the small intestines were examined to quantitate
      leukocyte adherence using intravital microscopy. In sham-operated rats (control),
      there was minimal to no leukocyte adherence throughout the experiment.
      Hemorrhagic shock resulted in significant leukocyte adherence during
      resuscitation (10.8 +/- 1.7 cells/100 microm, P < 0.01) when compared to control.
      Anti-LFA-1beta, when given before hemorrhagic shock, significantly attenuated
      leukocyte adherence during resuscitation (1.1 +/- 0.8, P < 0.01) when compared
      with hemorrhagic shock alone. This protective effect of anti-LFA-1beta on
      leukocyte adherence was even demonstrated when it was given during (1.6 +/- 0.3,
      P < 0.01) and 10 min after hemorrhagic shock (5.8 +/- 0.4, P < 0.05). These
      results suggest that anti-LFA-1beta may be of potential therapeutic benefit
      against microvascular injury caused by hemorrhagic shock.

PMID- 10909894
TI  - Interruption of hepatic gap junctional communication in the rat during
      inflammation induced by bacterial lipopolysaccharide.
AB  - Gap junctional cellular communication is important in the propagation of signals
      that coordinate hepatic metabolism. Hepatocytes express two different connexin
      (Cx) genes, Cx32 and Cx26, which encode for the subunit component of gap junction
      channels. Previous studies have shown that the expression of hepatic Cx32 is
      reduced during inflammatory conditions. The objective of this study was to
      evaluate whether this decrease in Cx32 expression results in a decrease in
      hepatic gap junctional communication. Transfer of the dye Lucifer Yellow between
      hepatocytes was measured after microinjection of single cells in an isolated
      perfused liver. Livers were harvested from rats subjected to an inflammatory
      condition induced by administration of bacterial lipopolysaccharide (LPS). A
      decrease in gap junctional cellular communication was observed within 6 h of the
      LPS treatment. This decrease in dye coupling was reversible, because gap
      junctional communication returned to control levels within 48 h of the LPS
      injection. The inhibition of hepatic gap junctional communication was associated
      with the disappearance of Cx32 and Cx26 from the hepatocyte plasma membrane as
      detected by indirect immunostaining. Cx32 mRNA levels were also reduced during
      inflammation as previously reported. However, Cx26 mRNA levels were unaffected or
      even transiently increased after the injection of LPS without significant
      increase in the polypeptide level. Thus, the down-regulation of Cx32 and Cx26
      from the hepatocyte surface is apparently due to a rapid degradation of the
      polypeptide from the cell surface. We hypothesize that this loss of gap
      junctional cellular communication within the liver may contribute to the
      disordered hepatic metabolic that occurs during inflammatory states.

PMID- 10909895
TI  - Terbutaline prevents circulatory failure and mitigates mortality in rodents with
      endotoxemia.
AB  - Septic shock is characterized by a decrease in systemic vascular resistance.
      Nevertheless, regional increases in vascular resistance can occur that may
      predispose mammals to organ dysfunction, including the acute respiratory distress
      syndrome. In the host infected by endotoxin (lipopolysaccharide, LPS), the
      expression and release of proinflammatory tumor necrosis factor-alpha (TNFalpha)
      rapidly increases, and this cytokine production is regulated by agents elevating
      cyclic AMP. In this report, we present evidence that terbutaline, a beta2
      agonist, inhibits TNFalpha production and enhances interleukin-10 (IL-10) release
      in the anesthetized rat treated with LPS. In addition, an overproduction of
      nitric oxide (NO, examined by its metabolites nitrite/nitrate) by inducible NO
      synthase (iNOS, examined by western blot analysis) is attenuated by pretreatment
      of LPS rats with terbutaline. Overall, pretreatment of rats with terbutaline
      attenuates the delayed hypotension and prevents vascular hyporeactivity to
      norepinephrine. In addition, pretreatment of mice with terbutaline also improves
      the survival in a model of severe endotoxemia. The infiltration of
      polymorphonuclear neutrophils into organs (e.g., lung and liver) from the
      surviving LPS mice treated with terbutaline was reduced almost to that seen in
      the normal controls. These findings suggest that the inhibition of TNFalpha and
      NO (via iNOS) production as well as the increment of IL-10 production contribute
      to the beneficial effect of terbutaline in animals with endotoxic shock.

PMID- 10909896
TI  - Endotoxemia alters splanchnic capacitance.
AB  - The splanchnic circulation constitutes a major portion of the total capacitance
      vasculature and may affect venous return and subsequently cardiac output during
      low output states. This study assessed the effects of rapid (10 microg/kg over 5
      min) and slow (10 microg/kg over 60 min) induction of endotoxin (Escherichia
      coli) shock on splanchnic blood volume in 8 farm swine. Blood volume was measured
      by using Tc99m-labeled erythrocytes and radionuclide imaging. Baseline arterial
      pressure (MAP), central venous pressure (CVP), and liver, splenic, mesenteric and
      total splanchnic volumes were stable during the 30-min baseline. Approximately 30
      min after the rapid endotoxin infusion, splenic volume decreased by 45%, whereas
      liver volume increased by 40% and MAP decreased by 60% (P < 0.01). The reduction
      in splenic volume occurred within 10 min of the endotoxin infusion, whereas liver
      volume changes occurred after MAP reduction. The slow endotoxin infusion also
      reduced splenic volume by approximately 50% (P = 0.05), whereas MAP declined by
      30% (P < 0.05). However, the slow endotoxin infusion lowered liver volume (P <
      0.05). Mesenteric volume was unaffected by the fast or slow endotoxin infusion.
      Total splanchnic volume was unaffected by the fast infusion but decreased by 37%
      in the slow infusion group (P < 0.05). In summary, E. coli endotoxin reduces
      splenic blood volume and increases liver blood volume after acute hypotension
      ensues. Endotoxin does not increase total splanchnic blood volume and may
      actually decrease total splanchnic volume in the absence of circulatory collapse.
      This endotoxin shock model is not associated with blood volume pooling in the
      splanchnic capacitance circulation.

PMID- 10909897
TI  - Procalcitonin and proinflammatory cytokine interactions in sepsis.
AB  - Immunoneutralization of procalcitonin (ProCT), a putative mediator of sepsis, has
      been shown to increase survival in an animal model of sepsis. To better
      understand the role that ProCT plays in the sepsis cascade, we studied the
      relationship of this hormone to the proximal proinflammatory mediators, IL-1beta
      and TNFalpha. Hamsters were made septic by i.p. implantation of Escherichia coli
      impregnated agar pellets. A time line study of serum IL-beta, TNFalpha, and ProCT
      levels showed that the increase in the cytokines was transient and less than 2
      fold over baseline, whereas ProCT increased >100-fold by 12 h and remains
      elevated through 24 h. TNFalpha (400 microg/kg) was injected into healthy
      animals, inducing an elevation in ProCT that was 25-fold greater than controls.
      ProCT (30 microg/kg) was given to healthy and septic animals. In healthy animals,
      there was no significant elevation in serum IL-1beta or TNFalpha levels. In
      septic animals, IL-1beta was modestly blunted at 3 h but not at 12 h, and there
      was no change in TNFalpha levels. ProCT did not initiate or enhance IL-1beta or
      TNFalpha expression; however, the massive and sustained elevation of this hormone
      seen in sepsis can be induced by the proximal cytokine, TNFalpha. This study
      suggests that ProCT is a secondary mediator that might augment and amplify but
      does not initiate the septic response. Immunoneutralization of ProCT may prove to
      be an important clinical strategy, in view of its sustained elevation and the
      difficulty in initiating therapy for sepsis during the early phases of illness.

PMID- 10909899
TI  - Neural tube closure in humans initiates at multiple sites: evidence from human
      embryos and implications for the pathogenesis of neural tube defects.
AB  - The closure of the neural tube (NT) in the human embryo has generally been
      described as a continuous process that begins at the level of the future cervical
      region and proceeds both rostrally and caudally. On the other hand, multiple
      initiation sites of NT closure have been demonstrated in mice and other animals.
      In humans, based on the study of neural tube defects (NTD) in clinical cases, van
      Allen et al. (1993) proposed a multisite NT closure model in which five closure
      sites exist in the NT of human embryos. In the present study, we examined human
      embryos in which the NT was closing (Congenital Anomaly Research Center, Kyoto
      University) grossly and histologically, and found that NT closure in human
      embryos initiates at multiple sites but that the mode of NT closure in humans is
      different from that in many other animal species. In addition to the future
      cervical region that is widely accepted as an initiation site of NT closure (Site
      A), the mesencephalic-rhombencephalic boundary was found to be another initiation
      site (Site B). The second closure initiating at Site B proceeds bidirectionally
      and its caudal extension meets the first closure from Site A over the
      rhombencephalon, and the rostral extension of the second closure meets another
      closure extending from the rostral end of the neural groove (Site C) over the
      prosencephalon, where the anterior neuropore closes. The caudal extension of the
      first closure initiating at Site A was found to proceed all the way down to the
      caudal end of the neural groove where the posterior neuropore is formed,
      indicating that in humans, NT closure does not initiate at the caudal end of the
      neural groove to proceed rostrally. Since there is a considerable species
      difference in the mode of NT closure, we should be careful when extrapolating the
      data from other animals to the human. It seems that the type of NTD affects the
      intrauterine survival of abnormal embryos. Almost all the embryos with total
      dysraphism appear to die by 5 weeks of gestation, those with an opening over the
      rhombencephalon by 6.5 weeks, and those with a defect at the frontal and parietal
      regions survive beyond 7 weeks.

PMID- 10909898
TI  - Morphological study of the tegmental pedunculopontine nucleus, substantia nigra
      and subthalamic nucleus, and their interconnections in rat organotypic culture.
AB  - The morphological organization of the tegmental pedunculopontine nucleus,
      midbrain extrapyramidal area, substantia nigra and subthalamic nucleus and their
      interrelationships were studied in rat organotypic culture using
      immunohistochemistry and NADPH-diaphorase histochemistry. Three coronal sections,
      one containing the tegmental pedunculopontine nucleus/midbrain extrapyramidal
      area, another with the substantia nigra and the third with the subthalamic
      nucleus, were obtained from postnatal 1-2-day-old rats. These sections were co
      cultured for 3-4 weeks using the roller-tube technique. In the tegmental
      pedunculopontine nucleus/midbrain extrapyramidal area, the distribution pattern
      of cholinergic neurons was similar to that found in the in vivo study. We could,
      therefore, identify the subdivisions of the tegmental pedunculopontine nucleus
      (i.e., pars compacta and pars dissipata) and the midbrain extrapyramidal area. As
      in the in vivo situation, glutamate immunoreactive neurons were also located in
      these areas. Approximately 10% of NADPH-diaphorase positive neurons in the
      tegmental pedunculopontine nucleus, were glutamate immunoreactive. In the
      substantia nigra, as in the in vivo, tyrosine hydroxylase immunoreactive
      (putative dopaminergic) neurons were identified predominantly in the substantia
      nigra pars compacta, and parvalbumin immunoreactive neurons (putative GABAergic)
      mainly in the substantia nigra pars reticulata. The subthalamic nucleus was
      ladened with glutamate immunoreactive neurons. NADPH-diaphorase stained axons
      originating from the tegmental pedunculopontine nucleus were traced into the
      substantia nigra and subthalamic nucleus. They were often in close apposition to
      tyrosine hydroxylase immunoreactive neurons in the substantia nigra. Parvalbumin
      immunoreactive fibers from the substantia nigra projected heavily to the midbrain
      extrapyramidal area, but only sparsely to the tegmental pedunculopontine nucleus
      and the subthalamic nucleus. These findings indicate that the tegmental
      pedunculopontine nucleus/midbrain extrapyramidal area, substantia nigra and
      subthalamic nucleus in the organotypic culture have retained a basic
      morphological organization and connectivity similar to those seen in the in vivo
      situation. Therefore, this preparation could be a useful model to conduct further
      studies to investigate functional circuits among the structures represented.

PMID- 10909900
TI  - Surface changes in the rat vomeronasal epithelium during degeneration and
      regeneration of sensory receptor cells.
AB  - To investigate cell turnover in the vomeronasal epithelium we used electron
      microscopy to obtain quantitative measurements of changes observed at the surface
      of the sensory epithelium. Receptor cell degeneration was induced by sensory
      nerve transection and animals were examined at postoperative recovery times of 2,
      4, 6, 10, 15, 35 and 60 days. We measured the number and density of receptor and
      supporting cells, and membrane length at the surface of the sensory epithelium.
      The number of receptor cells rapidly decreased during the degeneration period,
      reaching a minimum at 6 days. After 15 days of recovery the number and density of
      receptor cells returned to control levels. The surface membrane length for
      regenerated receptor cells was similar to that of controls, however the
      morphological appearance was characteristic of immature cells. In contrast to the
      receptor cells, the number and density of supporting cells did not change during
      degeneration and regeneration. However, there was a significant increase in the
      length of supporting cell-surface membranes. These results suggest that during
      receptor cell degeneration, supporting cell membranes compensate for the loss of
      receptor cells by expanding their surface membrane length to help to maintain the
      continuity of the epithelial surface. Thus, an important role of vomeronasal
      supporting cells may be to maintain the structural integrity of the epithelium
      during turnover of the receptor cell population.

PMID- 10909901
TI  - Morphological analysis of peripheral nerve regenerated by means of vein grafts
      filled with fresh skeletal muscle.
AB  - Clinical data have shown that a vein segment filled with fresh skeletal muscle
      can be considered a good autologous grafting conduit for the repair of peripheral
      nerve lesions. In this study, the long-term morphological organization of rat
      sciatic nerve fibers regenerated along a muscle-vein-combined graft conduit is
      further analysed by light and electron microscopy. Regenerated nerve fibers were
      organized into fascicles of various sizes that were clearly delimited by
      perineurial-like shells made by long and thin cytoplasmic processes of
      perineurial-like bipolar cells and by densely packed collagen fibrils. Grafted
      skeletal muscle fibers were still detectable among nerve fiber fascicles.
      However, in spite of the persistence of skeletal muscle along the graft,
      regenerated nerve fibers showed a good morphological pattern of regeneration,
      providing further evidence that the muscle-vein-combined grafting technique
      represents an effective surgical alternative to the classical fresh nerve
      autograft for the repair of peripheral nerve defects.

PMID- 10909902
TI  - Changes in expression of the lysosomal membrane glycoprotein, LAMP-1 in
      interdigital regions during embryonic mouse limb development, in vivo and in
      vitro.
AB  - Syndactyly, a failure of the digits to separate into individual units, affects
      about 8 to 9 per 1000 newborns and results from an aberration of the normal
      development of the interdigital tissues. Limb digit separation is the result of
      programmed cell death (apoptosis). Lysosomes play a role in the process of cell
      self-destruction. Our experiment was designed to test the hypothesis that the
      intensity of interdigital lysosomes increases during the separation of digits in
      vivo and in vitro. The primary mouse monoclonal antibody, 1D4B, detects the
      presence of lysosomes by identifying the LAMP-1 glycoprotein on the lysosome cell
      membrane. In our experiment this antibody immunodetected interdigital lysosome
      proteins in serial sections of limbs from Swiss-Webster mouse embryos,
      gestational ages E12.5 through E15, key developmental stages for digit
      separation. Digit separation was associated with an increase in intensity of
      lysosomal protein staining. In E12.5 limbs, the presence of lysosomes was
      enriched in the distal aspect of the interdigital tissue. However, the number of
      lysosomes markedly increased in the E13 and E14 limbs, including the entire
      length and width of the interdigital tissue in the E14 limbs. This lysosomal
      protein presence in E14 limbs was significant compared to E12.5, E13, and E15
      limbs. By day 12.5, the mouse embryo limb is committed to digit separation.
      Addition of retinoic acid to the culture medium of limbs earlier in development,
      such as E12, results in induction of the process of digit separation. Cultured
      E12 limbs that did not receive an addition of retinoic acid, did not show digit
      separation. We conclude that in the limb development process, the enrichment in
      interdigit LAMP-1 proteins, may indicate a relationship between lysosomes,
      apoptosis, and digit separation. We also conclude that retinoic acid has an
      important role in digit separation in vivo, as shown in limb development, and
      demonstrated through the addition of retinoic acid to media of cultured tissues.

PMID- 10909903
TI  - Nitrergic and peptidergic innervation in the developing rat heart.
AB  - The phenotypic expression and anatomic distribution of nitrergic and peptidergic
      innervation in the developing rat heart was localized by reduced nicotinamide
      adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and
      immunohistochemistry using antibodies against neuronal isoform of nitric oxide
      synthase (nNOS), neuropeptide Y (NPY) and calcitoningene-related peptide (CGRP).
      NPY-immunoreactive nerve fibers showed the earliest expression by 16 days of
      gestation, with preferential innervation of the nodal and perinodal areas,
      followed by the innervation of the valves and ventricles by postnatal day 7. NPY
      immunoreactivity was also localized to a large proportion of the intrinsic
      cardiac ganglia from 16 days of gestation onwards with a progressive increase in
      the number of neuronal cell bodies per ganglia with age. CGRP-positive nerve
      fibers appeared by 19 days of gestation and were less dense during the
      gestational and early postnatal periods, and showed a quantitative increase in
      density by 7 days, followed by a decrease by 3 weeks postnatal. None of the
      intrinsic ganglia were stained positive for CGRP, indicating the extrinsic
      sensory origin of these stained fibers. Nitrergic innervation paralleled the
      sensory innervation, with the cardiac ganglia and nerve fibers showing a positive
      labeling from 19 days of gestation onwards. NADPH-d and nNOS were partially co
      localized. Double-label immunohistochemistry showed that a considerable
      proportion of sensory CGRP-immunopositive fibers were also immunoreactive for
      NOS. The results of the present study show that neuropeptides and nitric oxide
      are expressed by the late gestational period and that autonomic efferent
      innervation precedes sensory and nitrergic innervation in the developing heart.

PMID- 10909904
TI  - Dorsoventral compartmentalization of mesoderm in heart-forming area of chick
      embryo.
AB  - In early chick development (stages 5-8) the seemingly homogeneous mesoderm in the
      heart-forming area splits to somatic and splanchnic cardiogenic layers. Little is
      known about dorsoventral compartmentalization before splitting. Electron
      microscopic analysis shows the early dorsoventral polarization of
      precardiomyocytes. The dorsal compartment has epithelial and the ventral
      compartment mesenchymal features with numerous protrusions. At stage 5+-6
      staining for wheat germ agglutinine (WGA) transiently demarcates the ventral part
      of mesoderm. The glycosomes (beta-glycogen) show a dorsoventral gradient in the
      mesoderm of the cardiogenic field during the initial step of the compaction. The
      differential expression of glycosomes depends on the activity of glycogen
      synthase kinase 3-beta, a component of the wnt-signaling pathway, and might in
      this spatiotemporal developmental window be involved in the commitment of
      presumptive cardiogenic and somatic cells. To verify this hypothesis simulation
      experiments with LiCl in vitro were carried out. The normal splitting of the
      mesoderm and the development of heart primordia were disturbed. Blocking the
      receptors of WGA by WGA in vitro at stage 5-5+ perturbs the migration of mesoderm
      to anterio-medial direction. It appears that early specification of dorsal and
      ventral compartments of the mesoderm in the heart-forming area correlates with
      the gradient of glycosomes. Our results suggest that the target of LiCl action
      (glycogen synthase kinase 3-beta) might be involved in the specification of heart
      primordia and that WGA receptors mediate the migration of mesoderm to the
      anteriomedial direction.

PMID- 10909905
TI  - Developmental changes of NADPH-diaphorase positive structures in the isthmic
      nuclei of the chick.
AB  - Nicotine adenine dinucleotide phosphate-diaphorase staining was used to study
      nitric oxide synthase activity and distribution in the midbrain visual structures
      of white leghorn chick embryos and post-hatched chickens. Enzyme staining first
      appeared in the isthmic region at the tenth embryonic day (E10) in the neuropil
      of the nucleus isthmi, pars parvocellularis. At E11 faint enzyme positivity
      appeared also in the nucl. isthmi pars magnocellularis, the nucl. semilunaris and
      the nucl. isthmo-opticus. The staining intensity of the isthmic nuclei
      dramatically increased between the 12.5th and the 13th days of incubation. The
      nucl. isthmi, pars parvocellularis showed the strongest enzyme reaction
      throughout embryonic life. A day before hatching all the isthmic nuclei were
      heavily stained, however, nicotine adenine dinucleotide phosphate-diaphorase
      positive cells occurred exclusively in the nucleus isthmo-opticus. In the tectum
      opticum, intensely stained cells occupied the stratum fibrosum et griseum
      superficiale. The layer containing the projection neurons to the isthmo-optic
      nucleus was unstained. In the isthmic region, the intensity of staining surpassed
      that of the tectum and reached its maximum at E17 and then slowly decreased till
      the end of the experimental period (120 days post-hatched). The tractus isthmo
      opticus showed nicotine adenine dinucleotide phosphate-diaphorase activity
      throughout the investigated period of life of the chicken, but the tractus
      tectoisthmo-opticus was unstained. Our results suggest that in the isthmic
      nuclei, nicotine adenine dinucleotide phosphate-diaphorase-positive neurons occur
      only in the isthmo-optic nucleus and optic tectum. The other positively stained
      structures are the fibers and terminals of tectal cells. In most brain areas
      nicotine adenine dinucleotide phosphate-diaphorase indicates nitric oxide
      synthase that produces nitric oxide. The transient appearance of this molecule is
      probably necessary for neuronal differentiation or the establishment of synaptic
      connections in the isthmic nuclei, and these developmental changes are under the
      control of the optic tectum.

PMID- 10909906
TI  - Comparison of in vitro activity of danofloxacin, florfenicol, oxytetracycline,
      spectinomycin and tilmicosin against recent field isolates of Mycoplasma bovis.
AB  - The minimum inhibitory concentrations (MICS) and minimum mycoplasmacidal
      concentrations (MMCs) of danofloxacin, florfenicol, oxytetracycline,
      spectinomycin and tilmicosin against 62 recent British field isolates of
      Mycoplasma bovis were determined in vitro by a broth microdilution method. The
      isolates were most susceptible todanofloxacin with MIC90 and MMC90 values of 0.5
      microg/ml and 1.0 microg/ml, respectively. They were less susceptible to
      florfenicol with a MIC90 of 16 microg/ml and MMC90 of 32 microg/ml.
      Oxytetracycline and spectinomycin had only a limited effect against the majority
      of isolates tested with MIC50s of 32 microg/ml and 4 microg/ml, respectively and
      MIC90s of 64 microg/ml and more than 128 microg/ml, respectively. Nearly 20 per
      cent of the isolates were highly resistant to spectinomycin, and tilmicosin was
      ineffective, with 92 per cent of the isolates having MIC values of 128 microg/ml
      or greater. There was no evidence of resistance by M bovis to danofloxacin.

PMID- 10909907
TI  - Congenital arthrogryposis: an inherited limb deformity in pedigree Suffolk lambs.
AB  - Thirty of 52 pedigree Suffolk lambs (58 per cent) were born with arthrogryposis
      characterised by bilateral flexion rigidity of the metacarpophalangeal and carpal
      joints. The recent introduction of a breeding ram was identified as the only
      significant risk factor in the flock, and embryo transfer was used to test the
      hypothesis that the arthrogryposis was an inherited disorder associated with the
      introduction of this ram. Two adult ewes that had previously produced lambs with
      arthrogryposis by the ram and four of its affected daughters were available as
      donors, and 20 crossbred ewes were used as recipients. Ten Suffolk-crossed ewes
      that had no known familial relationship with the ram were also mated by the ram
      as controls and they produced 10 normal lambs. Following embryo transfer, 19
      lambs were born, of which seven were stillborn; arthrogryposis was evident in 10
      of the 12 live lambs. Analysis of the data suggested that in the population under
      study, arthrogryposis was inherited as an autosomal recessive condition.

PMID- 10909908
TI  - Observations on the trajectory of the bullet in 15 horses euthanased by free
      bullet.
AB  - The trajectories taken by the free bullets used to euthanase 15 horses were
      examined. The point of entry of the bullet relative to the recommended site was
      measured, together with the angle of the trajectory of the bullet relative to a
      tangent to its point of entry, the deviation of the trajectory from the midline
      of the brain, the structures of the brain that were damaged and the extent of
      this damage. Despite a reasonably consistent point of entry, there were wide
      variations in the damage inflicted, ranging from the total destruction of the
      hindbrain to injury to the cerebral cortex alone. The extent of the bullet's
      lateral deviation from the midline appeared to be the most significant factor
      affecting the level of destruction to the hindbrain, suggesting that angular
      direction may be more important than precise surface location in effecting a
      satisfactory kill.

PMID- 10909909
TI  - Attitude of Swedish veterinary and medical students to animal experimentation.
AB  - Nearly all veterinary and medical students (94 per cent) found it morally
      acceptable to use animals in research and believed it to be a necessity in order
      to treat human diseases. In contrast with the medical students a substantial
      proportion of veterinary students (40 per cent) considered themselves animal
      rights activists. Unlike the medical curriculum, the veterinary curriculum
      contains a two-week course in laboratory animal medicine, and a higher proportion
      of the students who had not been through this course was opposed to the use of
      animals in research than of the students who had completed the course. The course
      modified the views of half the students; more than 26 per cent of them became
      more positive towards animal use in research after the course, whereas 3 per cent
      became more negative.

PMID- 10909910
TI  - Changes in vaginal microbiology associated with the use of progesterone-releasing
      intravaginal devices.

PMID- 10909911
TI  - Serum antibodies to porcine circovirus type 1 and type 2 in pigs with and without
      PMWS.

PMID- 10909912
TI  - Crenosoma vulpis, the fox lungworm, in a dog in Ireland.

PMID- 10909913
TI  - Preliminary investigation committee findings.

PMID- 10909914
TI  - Badgers and TB in cattle.

PMID- 10909915
TI  - RCVS review of the veterinary nurse training scheme.

PMID- 10909916
TI  - Use of lignocaine in food animals.

PMID- 10909917
TI  - Out-of-hours calls.

PMID- 10909918
TI  - Megabacteria in mammals.

PMID- 10909919
TI  - Newcastle disease in Italy.

PMID- 10909920
TI  - Sweet itch research project.

PMID- 10909921
TI  - Recent developments in iterative image reconstruction for PET and SPECT.

PMID- 10909922
TI  - Noise characterization of block-iterative reconstruction algorithms: I. Theory.
AB  - Researchers have shown increasing interest in block-iterative image
      reconstruction algorithms due to the computational and modeling advantages they
      provide. Although their convergence properties have been well documented, little
      is known about how they behave in the presence of noise. In this work, we fully
      characterize the ensemble statistical properties of the rescaled block-iterative
      expectation-maximization (RBI-EM) reconstruction algorithm and the rescaled block
      iterative simultaneous multiplicative algebraic reconstruction technique (RBI
      SMART). Also included in the analysis are the special cases of RBI-EM, maximum
      likelihood EM (ML-EM) and ordered-subset EM (OS-EM), and the special case of RBI
      SMART, SMART. A theoretical formulation strategy similar to that previously
      outlined for ML-EM is followed for the RBI methods. The theoretical formulations
      in this paper rely on one approximation, namely, that the noise in the
      reconstructed image is small compared to the mean image. In a second paper, the
      approximation will be justified through Monte Carlo simulations covering a range
      of noise levels, iteration points, and subset orderings. The ensemble statistical
      parameters could then be used to evaluate objective measures of image quality.

PMID- 10909923
TI  - Interior-point methodology for 3-D PET reconstruction.
AB  - Interior-point methods have been successfully applied to a wide variety of linear
      and nonlinear programming applications. This paper presents a class of
      algorithms, based on path-following interior-point methodology, for performing
      regularized maximum-likelihood (ML) reconstructions on three-dimensional (3-D)
      emission tomography data. The algorithms solve a sequence of subproblems that
      converge to the regularized maximum likelihood solution from the interior of the
      feasible region (the nonnegative orthant). We propose two methods, a primal
      method which updates only the primal image variables and a primal-dual method
      which simultaneously updates the primal variables and the Lagrange multipliers. A
      parallel implementation permits the interior-point methods to scale to very large
      reconstruction problems. Termination is based on well-defined convergence
      measures, namely, the Karush-Kuhn-Tucker first-order necessary conditions for
      optimality. We demonstrate the rapid convergence of the path-following interior
      point methods using both data from a small animal scanner and Monte Carlo
      simulated data. The proposed methods can readily be applied to solve the
      regularized, weighted least squares reconstruction problem.

PMID- 10909924
TI  - Fast maximum entropy approximation in SPECT using the RBI-MAP algorithm.
AB  - In this work, we present a method for approximating constrained maximum entropy
      (ME) reconstructions of SPECT data with modifications to a block-iterative
      maximum a posteriori (MAP) algorithm. Maximum likelihood (ML)-based
      reconstruction algorithms require some form of noise smoothing. Constrained ME
      provides a more formal method of noise smoothing without requiring the user to
      select parameters. In the context of SPECT, constrained ME seeks the minimum
      information image estimate among those whose projections are a given distance
      from the noisy measured data, with that distance determined by the magnitude of
      the Poisson noise. Images that meet the distance criterion are referred to as
      feasible images. We find that modeling of all principal degrading factors
      (attenuation, detector response, and scatter) in the reconstruction is critical
      because feasibility is not meaningful unless the projection model is as accurate
      as possible. Because the constrained ME solution is the same as a MAP solution
      for a particular value of the MAP weighting parameter, beta, the constrained ME
      solution can be found with a MAP algorithm if the correct value of beta is found.
      We show that the RBI-MAP algorithm, if used with a dynamic scheme for estimating
      beta, can approximate constrained ME solutions in 20 or fewer iterations. We
      compare results for various methods of achieving feasible images on a simulation
      of Tl-201 cardiac SPECT data. Results show that the RBI-MAP ME approximation
      provides images and quantitative estimates close to those from a slower algorithm
      that gives the true ME solution. Also, we find that the ME results have higher
      spatial resolution and greater high-frequency noise content than a feasibility
      based stopping rule, feasibility-based low-pass filtering, and a quadratic Gibbs
      prior with beta selected according to the feasibility criterion. We conclude that
      fast ME approximation is possible using either RBI-MAP with the dynamic procedure
      or a feasibility-based stopping rule, and that such reconstructions may be
      particularly useful in applications where resolution is critical.

PMID- 10909926
TI  - On the optimality of the gridding reconstruction algorithm.
AB  - Gridding reconstruction is a method to reconstruct data onto a Cartesian grid
      from a set of nonuniformly sampled measurements. This method is appreciated for
      being robust and computationally fast. However, it lacks solid analysis and
      design tools to quantify or minimize the reconstruction error. Least squares
      reconstruction (LSR), on the other hand, is another method which is optimal in
      the sense that it minimizes the reconstruction error. This method is
      computationally intensive and, in many cases, sensitive to measurement noise.
      Hence, it is rarely used in practice. Despite their seemingly different
      approaches, the gridding and LSR methods are shown to be closely related. The
      similarity between these two methods is accentuated when they are properly
      expressed in a common matrix form. It is shown that the gridding algorithm can be
      considered an approximation to the least squares method. The optimal gridding
      parameters are defined as the ones which yield the minimum approximation error.
      These parameters are calculated by minimizing the norm of an approximation error
      matrix. This problem is studied and solved in the general form of approximation
      using linearly structured matrices. This method not only supports more general
      forms of the gridding algorithm, it can also be used to accelerate the
      reconstruction techniques from incomplete data. The application of this method to
      a case of two-dimensional (2-D) spiral magnetic resonance imaging shows a
      reduction of more than 4 dB in the average reconstruction error.

PMID- 10909925
TI  - Left ventricular motion reconstruction based on elastic vector splines.
AB  - In medical imaging it is common to reconstruct dense motion estimates, from
      sparse measurements of that motion, using some form of elastic spline (thin-plate
      spline, snakes and other deformable models, etc.). Usually the elastic spline
      uses only bending energy (second-order smoothness constraint) or stretching
      energy (first-order smoothness constraint), or a combination of the two. These
      elastic splines belong to a family of elastic vector splines called the Laplacian
      splines. This spline family is derived from an energy minimization functional,
      which is composed of multiple-order smoothness constraints. These splines can be
      explicitly tuned to vary the smoothness of the solution according to the
      deformation in the modeled material/tissue. In this context, it is natural to
      question which members of the family will reconstruct the motion more accurately.
      We compare different members of this spline family to assess how well these
      splines reconstruct human cardiac motion. We find that the commonly used splines
      (containing first-order and/or second-order smoothness terms only) are not the
      most accurate for modeling human cardiac motion.

PMID- 10909927
TI  - 3-D reconstruction of coronary arterial tree to optimize angiographic
      visualization.
AB  - Due to vessel overlap and foreshortening, multiple projections are necessary to
      adequately evaluate the coronary tree with arteriography. Catheter-based
      interventions can only be optimally performed when these visualization problems
      are successfully solved. The traditional method provides multiple selected views
      in which overlap and foreshortening are subjectively minimized based on two
      dimensional (2-D) projections. A pair of images acquired from routine
      angiographic study at arbitrary orientation using a single-plane imaging system
      were chosen for three-dimensional (3-D) reconstruction. After the arterial
      segment of interest (e.g., a single coronary stenosis or bifurcation lesion) was
      selected, a set of gantry angulations minimizing segment foreshortening was
      calculated. Multiple computer-generated projection images with minimized segment
      foreshortening were then used to choose views with minimal overlapped vessels
      relative to the segment of interest. The optimized views could then be utilized
      to guide subsequent angiographic acquisition and interpretation. Over 800 cases
      of coronary arterial trees have been reconstructed, in which more than 40 cases
      were performed in room during cardiac catheterization. The accuracy of 3-D length
      measurement was confirmed to be within an average root-mean-square (rms) 3.5%
      error using eight different pairs of angiograms of an intracoronary guidewire of
      105-mm length with eight radiopaque markers of 15-mm interdistance. The accuracy
      of similarity between the additional computer-generated projections versus the
      actual acquired views was demonstrated with the average rms errors of 3.09 mm and
      3.13 mm in 20 LCA and 20 RCA cases, respectively. The projections of the
      reconstructed patient-specific 3-D coronary tree model can be utilized for
      planning optimal clinical views: minimal overlap and foreshortening. The
      assessment of lesion length and diameter narrowing can be optimized in both
      interventional cases and studies of disease progression and regression.

PMID- 10909928
TI  - Fast delineation and visualization of vessels in 3-D angiographic images.
AB  - A method is presented which aids the clinician in obtaining quantitative measures
      and a three-dimensional (3-D) representation of vessels from 3-D angiographic
      data with a minimum of user interaction. Based on two user defined starting
      points, an iterative procedure tracks the central vessel axis. During the
      tracking process, the minimum diameter and a surface rendering of the vessels are
      computed, allowing for interactive inspection of the vasculature. Applications of
      the method to CTA, contrast enhanced (CE)-MRA and phase contrast (PC)-MRA images
      of the abdomen are shown. In all applications, a long stretch of vessels with
      varying width is tracked, delineated, and visualized, in less than 10 s on a
      standard clinical workstation.

PMID- 10909929
TI  - Localization of epileptogenic zones in F-18 FDG brain PET of patients with
      temporal lobe epilepsy using artificial neural network.
AB  - For an objective interpretation of cerebral metabolic pattern to find
      epileptogenic zones in patients with temporal lobe epilepsy (TLE), we developed a
      computer-aided classifier using an artificial neural network (ANN). We studied
      261 epilepsy patients diagnosed as no abnormal findings (NA, n = 64), left TLE (n
      = 116), or right TLE (n = 81) on interictal brain F-18-fluorodeoxyglucose
      positron emission tomography (FDG PET) by the consensus of two expert physicians.
      Seventeen asymmetry indexes between the mean counts of the 34 mirrored regions
      were extracted from the spatially normalized images and used as input parameters.
      The three diagnoses of NA, left TLE, and right TLE were used as outputs of the
      ANN. The structure of the ANN was optimized with variable error goals and the
      number of hidden units. On the criteria of agreement of diagnoses with those of
      expert viewers, the best classifier was chosen, which yielded a maximum average
      agreement of 85% for the test set when we used an error goal of 20 (sum of
      squared error) and ten hidden units. We could devise an ANN that performed as
      well in diagnosing left or right TLE on FDG PET as human experts and could be
      used as a clinical decision support tool.

PMID- 10909930
TI  - The future of academic surgery.

PMID- 10909931
TI  - The impact of coronary stenting on immediate procedural complication and long
      term clinical restenosis at Waikato Hospital.
AB  - AIM: Clinical data on coronary stenting from within New Zealand is scarce and, in
      particular, the impact of current stent technologies is unknown. We reviewed all
      angioplasties undertaken at Waikato Hospital over a two year period to determine
      the clinical effect of coronary stenting on the local population. METHODS: Data
      from all patients who underwent coronary angioplasty at Waikato Hospital between
      July 1, 1995 and July 1, 1997 were included. Stents were deployed either to
      remedy sub-optimal results, or were electively used for saphenous vein grafts or
      restenotic lesions. Patient follow-up was obtained through a combination of
      database review, chart search and GP or patient contact. RESULTS: 662 lesions
      were dilated in 441 patients. 91 lesions were stented, 52.7% for sub-optimal
      results following balloon angioplasty. 98% of patients were followed up at six
      months. Whilst procedural success rate was higher in stented patients compared to
      unstented patients (96.7% vs 87.5% respectively, p=0.009) the in-hospital sub
      acute occlusion rate was also increased (6.8% vs 1.9% respectively, p=0.007). At
      six months, coronary restenosis requiring repeat angioplasty was infrequent
      (10.9% overall) with no significant difference between the two groups (8.1% vs.
      11.2% for stented vs unstented patients respectively, p=NS). CONCLUSIONS: The use
      of stents appears effective in improving immediate procedural success rates.
      Despite stented patients being at higher risk initially, their complication and
      six month clinical restenosis rates were similar.

PMID- 10909932
TI  - Problem gamblers: do GPs want to intervene?
AB  - AIM: To survey GPs' attitudes towards problem gamblers and knowledge to
      successfully intervene. METHODS: 100 GPs, randomly selected for gender and
      geographical distribution, were anonymously surveyed by questionnaire through the
      Royal New Zealand College of General Practitioners. RESULTS: 80 GPs responded
      (80% of those surveyed). There was strong support (85%) for problem gambling
      being within a GP's mandate, for involvement in treatment of problem gambling
      (72%) and for their having a role in supporting a family where a member has a
      gambling problem (80%). There was less confidence in: raising the issue of
      gambling with patients (53%), in knowledge of resources (38%) and in having the
      necessary training to intervene (19%). CONCLUSIONS: GPs see problem gambling as a
      legitimate role for their intervention, however, they have concerns around their
      competency and knowledge of resources. The provision of undergraduate and
      postgraduate training may assist to remove barriers to an accepted role in
      primary health.

PMID- 10909933
TI  - Some influences on cognitive development in a group of very low birthweight
      infants at four years.
AB  - AIM: To report the findings of an audit of 91 < 1,500 grams birthweight children
      at four years of age and consider the cognitive and behavioural results in the
      light of gestation, birthweight and socio-economic status. METHOD: Children born
      in 1993 were assessed using the Stanford-Binet Intelligence Scale, Conners'
      Parent Rating Scales and clinical evaluation. Parent interview provided further
      information on development, health and behaviour. RESULTS: Significant
      differences were demonstrated in a number of comparisons. For the Stanford-Binet
      results, children >28 weeks gestation obtained higher mean scores than those of
      shorter gestation for Abstract Visual Reasoning (representing cognitive skills
      such as spatial perception and visual - motor coordination), and Quantitative
      Reasoning (which includes numerical ability). In the case of birthweight, the
      mean score for children > or = 1,000 grams was higher on Quantitative Reasoning
      than that obtained by the lower birthweight group. When socioeconomic status
      classification was introduced, a number of differences in test scores were
      apparent, with children whose parents were in the lowest classification
      consistently performing less well. Quality of language results followed the same
      pattern. Analysis of the Conners' Scales identified this low socio-economic
      status group as having more learning problems and higher scores on the
      Hyperactivity Index than those whose parents were in the highest socioeconomic
      status group. CONCLUSION: Results for cognitive performance on the Stanford-Binet
      Scale were within one standard deviation of the mean, for the study population as
      a group. However, findings suggested that children <1,000 grams birthweight, or
      <28 weeks gestation, and those <1,500 grams with parents in the lowest socio
      economic group, were at particular risk of achieving lower scores prior to school
      entry. Their pattern of cognitive ability and behaviour could inhibit their
      adjustment to formal education when complex concepts require problem solving at a
      more advanced level.

PMID- 10909934
TI  - Health researchers' views of ethics committee functioning in New Zealand.
AB  - AIMS: To find out, from the perspective of researchers, how ethics committees are
      dealing with matters of ethical concern in research on humans and to seek the
      views of researchers on their role in thinking through the ethical issues in
      research. METHODS: A sample of researchers was selected from the Health Research
      Council database of grant recipients. Information was sought, using a mailed
      questionnaire, in relation to essential elements of concern to ethics committees
      according to the 1996 National Standard, types of study undertaken, codes of
      practice, national application forms, multicentre review, aspects of committee
      function and the role of researchers. RESULTS: The response rate was 35/40
      (87.5%). Approximately half the respondents commented favourably on most aspects
      of ethics committee functioning. Major criticisms were directed at the assessment
      of risks and benefits, scientific validity and handling of consent procedures.
      Consistent weaknesses in multicentre review, quality of advice and the
      composition of committees were noted. Positive aspects were: availability of
      chairpersons for discussion, the protection of vulnerable participants, the
      handling of the Health Information Privacy Code and the introduction of a
      national application form. Most researchers expected to take a major role in
      thinking through the ethical issues in their work. Half reported occasions where
      ethics committees had unnecessarily impeded research. CONCLUSIONS: The high level
      of commitment of researchers to ethics should be acknowledged by involving them
      more in guideline development and education. Perceived deficiencies in the range
      of expertise on ethics committees, particularly expertise to judge potential
      harms in experimental research, should be further investigated and addressed.
      Recommendations to improve the quality of ethical review include reducing the
      overload on committees by identifying categories of research which might not
      require full ethics committee review.

PMID- 10909935
TI  - Communicating information about sore throats and rheumatic fever to South
      Auckland high-school students.
AB  - AIMS: The present study examined the effectiveness of three modes of
      communication designed to increase high school students' knowledge about throat
      infections and rheumatic fever in a high risk area. METHODS: The study was part
      of an evaluation of a rheumatic fever prevention programme that has established
      27 school-based 'sore throat' clinics in South Auckland. The rationale for the
      clinics was explained to students through: assemblies conducted by public health
      nurses, written information sheets and classroom lessons. The effectiveness of
      each communication mode was assessed by comparing the knowledge of students from
      eight classes at an intervention school with eight classes at a control school
      before and after the intervention school students received the teaching. RESULTS:
      Students at the intervention school showed a significant improvement in knowledge
      compared to students at the control school. The assembly presentations by health
      professionals were more effective in informing students than information sheets
      or classroom lessons. CONCLUSIONS: This study suggests that presentations by
      health professionals are an effective method of teaching basic health information
      to students in these South Auckand secondary schools. Classroom teachers need to
      be provided with appropriate resources, if they are to provide effective
      instruction. Written information sheets should not be relied on.

PMID- 10909936
TI  - Investigation of the prevalence of Legionella species in domestic hot water
      systems.
AB  - AIMS: To investigate the prevalence of Legionella spp. in the hot water systems
      of a representative sample of Wellington domestic residences with electrically
      heated hot water systems, and to investigate risk factors (eg water temperature,
      plumbing materials) for such contamination. METHOD: 100 households with
      electrically heated hot water systems in the Wellington area were investigated.
      Samples of hot water from several hot water outlets were collected, and
      characteristics of the plumbing system were recorded. Water samples and swabs
      were cultured and further examined by polymerase chain reaction (PCR) and direct
      fluorescence antibody (DFA) testing to identify Legionella spp. and serogroups.
      RESULTS: No Legionella spp. were isolated by culture. PCR tested positive for
      Legionella in specimens from twelve residences. Six of these were also positive
      by DFA testing. The only environmental factor found to be associated with the
      presence of Legionella was recent plumbing work on the hot water system. Five of
      the twelve PCR-positive residences, and four of the six DFA-confirmed residences
      had hot water delivery temperatures in excess of 60 degrees C. CONCLUSIONS: The
      results suggest that either Legionellae colonise domestic hot water reticulation
      systems and/or that the organisms are killed during passage through the hot water
      tank. Both possibilities may be correct. Further work to characterise the
      microbial ecology of Legionella-positive hot water distribution systems would be
      useful, as would the development of improved methods for culturing the organisms
      from potable water.

PMID- 10909937
TI  - Nosocomial pneumonia in adult general medical and surgical patients at
      Christchurch Hospital.
AB  - AIMS: To determine the incidence, microbial cause, and outcome of nosocomial
      pneumonia in adult general medical and surgical patients at Christchurch
      Hospital. METHOD: A one-year prospective study of consecutive patients developing
      nosocomial pneumonia in a university-affiliated hospital. Expanded diagnostic
      laboratory testing was undertaken to identify the microbial cause of pneumonia.
      RESULTS: We recruited 126 patients, which represented an incidence of 6.1 per
      1,000 admissions. Only 52 (41%) patients submitted sputum that satisfied the
      cytological screening criteria for testing. A microbial cause was identified in
      47 cases (37%): the most common was Legionella spp. (sixteen cases), followed by
      Influenza A (six cases) and Staphylococcus aureus (four cases). We did not
      identify an environmental source of the Legionella species. Fourteen patients
      (11%) died as a consequence of pneumonia and nearly all of these had significant
      comorbidity. Renal impairment, alcohol excess, and severity of pneumonia were the
      most powerful predictors of a fatal outcome by univariate analysis. CONCLUSIONS:
      In most patients we did not identify a microbial cause of pneumonia; when we did,
      Legionella species were the most common, although this micro-organism has a long
      incubation period so some subjects may have acquired it before admission. These
      results guide preventative efforts, diagnostic testing and selection of
      antimicrobial therapy for nosocomial pneumonia in our hospital.

PMID- 10909938
TI  - Patients with infectious gastroenteritis in New Zealand rarely need antimicrobial
      treatment.

PMID- 10909939
TI  - Controlling pertussis in New Zealand by improving our immunisation rate.

PMID- 10909940
TI  - Gastrogate: the ethical responsibilities of doctors and administrators.

PMID- 10909942
TI  - Medical practitioner guilty of conviction.

PMID- 10909941
TI  - Soy formulas and the effects of isoflavones on the thyroid.

PMID- 10909943
TI  - Informed consent.

PMID- 10909944
TI  - Removal of name following convictions.

PMID- 10909946
TI  - Comparison of National Death Index and World Wide Web death searches.
AB  - The authors used the National Death Index and a World Wide Web Internet site that
      searches the Social Security Administration master files of deaths to determine
      the mortality status of 1,000 US subjects from the College Alumni Health Study.
      Subjects were classified as definitely dead, possibly dead, or presumed alive. Of
      246 definite deaths pinpointed by the National Death Index, the World Wide Web
      identified 94.7% of them. Of 438 men presumed alive according to the National
      Death Index, the World Wide Web identified 97.5% of them. However, the World Wide
      Web was not useful for identifying deaths of women. This study demonstrated that
      the World Wide Web may provide an alternative, inexpensive method of determining
      the mortality status of subjects in relatively small epidemiologic studies.

PMID- 10909945
TI  - Randomized controlled trial of audio computer-assisted self-interviewing: utility
      and acceptability in longitudinal studies. HIVNET Vaccine Preparedness Study
      Protocol Team.
AB  - Recent studies have reported on the utility of audio computer-assisted self
      interviewing (ACASI) in surveys of human immunodeficiency virus (HIV) risk
      behaviors that involve a single assessment. This paper reports the results of a
      test of ACASI within a longitudinal study of HIV risk behavior and infection.
      Study participants (gay men (n = 1,974) and injection drug users (n = 903)) were
      randomly assigned to either ACASI or interviewer-administered assessment at their
      second follow-up visit 12 months after baseline. Significantly more of the
      sexually active gay men assessed via ACASI reported having sexual partners who
      were HIV antibody positive (odds ratio = 1.36, 95% confidence interval: 1.08,
      1.72), and a higher proportion reported unprotected receptive anal intercourse.
      Among injection drug users (IDUs), our hypothesis was partially supported.
      Significantly more IDUs assessed via ACASI reported using a needle after another
      person without cleaning it (odds ratio = 2.40, 95% confidence interval: 1.34,
      4.30). ACASI-assessed IDUs reported similar rates of needle sharing and needle
      exchange use but a lower frequency of injection. Participants reported few
      problems using ACASI, and it was well accepted among members of both risk groups.
      Sixty percent of the participants felt that the ACASI elicited more honest
      responses than did interviewer-administered questionnaires. Together, these data
      are consistent with prior research findings and suggest that ACASI can enhance
      the quality of behavioral assessment and provide an acceptable method for
      collecting self-reports of HIV risk behavior in longitudinal studies and clinical
      trials of prevention interventions.

PMID- 10909947
TI  - Cocaine use during pregnancy and intrauterine growth retardation: new insights
      based on maternal hair tests.
AB  - Prenatal cocaine use is more accurately measured by maternal hair assay than by
      urine toxicology screening or self-report. To investigate the consequences of
      improved measurement, the authors ascertained cocaine use during pregnancy by
      maternal hair test, urine test, and self-report in a sample of 691 patients
      recruited from one New York City hospital in 1990-1992. Associations with
      intrauterine growth retardation, head circumference, and length of gestation were
      investigated. A positive hair test at delivery was not more strongly associated
      with birth weight (-38.1 g; 95% CI: -164, 88.3) or head circumference (-1.73 mm;
      95% CI: -5.91, 2.44) than a positive urine test at delivery (-182 g (95% CI: 
      295, -69.8) and -6.11 mm (95% CI: -9.99, -2.24), respectively). Cocaine
      concentration in hair (which was higher if urine tests were positive) had a dose
      response relationship with birth weight: a 27-g decrease (95% CI: -51.9, -1.04)
      with each log-unit increase in concentration. Birth weights were similar among
      infants of never users and infants of users who stopped using cocaine before
      delivery. Heavier use of cocaine, but not lighter use, was associated with
      intrauterine growth retardation, and exposure in late pregnancy was necessary to
      the association. Although maternal hair tests were instrumental in clarifying
      these relations, their clinical use is probably not warranted.

PMID- 10909948
TI  - Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children
      with birth weights less than 1,750 grams.
AB  - The authors examined the relation between intrapartum magnesium sulfate exposure
      and risk of cerebral palsy in a case-control study of low birth weight children
      designed to control for confounding by the clinical indications for magnesium in
      pregnancy. Case children (n = 97) included all singleton children with cerebral
      palsy who were born in 1985-1989 in Atlanta, Georgia with a birth weight less
      than 1,750 g and whose mothers had not had a hypertension-related disease during
      pregnancy. Control children (n = 110) were randomly selected from the infant
      survivors using identical selection criteria. Data on magnesium sulfate exposure,
      labor and delivery, and infant characteristics were abstracted from hospital
      records. The authors found no association between exposure to magnesium sulfate
      and cerebral palsy risk (odds ratio = 0.9; 95% confidence interval: 0.3, 2.6)
      either in all children or in subgroups with varying likelihoods for exposure to
      magnesium. However, the association did vary by birth weight, with a protective
      effect being seen in children born weighing less than 1,500 g and an elevated
      risk in children with birth weights of 1,500 g or more; all confidence intervals
      included 1.0 except for the combined <1,500 g group. Several ongoing randomized
      clinical trials of magnesium and cerebral palsy may shed more definitive light on
      this relation.

PMID- 10909949
TI  - Critical growth phases for adult shortness.
AB  - Previous growth studies have not explored how different growth phases-the fetal,
      infancy, childhood, and puberty phases-interact with each other in the
      development of adult shortness. In this paper, the authors attempt to describe
      the importance of each growth phase for adult shortness and the effect of growth
      in one phase on other, subsequent phases. The authors analyzed data from a
      longitudinal population-based growth study of 2,850 healthy, full term Swedish
      children born between 1973 and 1975. The height values were transformed into a
      centimeter score (CMS) by subtracting the raw values from the reference mean
      values for a particular age and sex. Subnormal growth in any growth phase, as
      defined by a decrease of 3 CMS or more during a growth phase, was associated with
      significant increased risk for final heights below 0, -6, and -12 CMS. For
      children with subnormal growth during one, two, and three phases, the percentages
      for final height below -12 CMS (a standard deviation score of approximately -2)
      were 0.5%, 9.4%, and 75%, respectively. Most children (57/62) with a final height
      below -12 CMS had subnormal growth in two or three phases. Height gains during
      the four growth phases were interdependent. The infancy phase was negatively
      associated with fetal growth (r = -0.33, p < 0.01); the childhood phase was
      positively associated with infancy growth (r = 0.21, p < 0.01); and the puberty
      phase was negatively associated with childhood growth (r = -0.10, p < 0.01).

PMID- 10909950
TI  - Glucose intolerance and physical inactivity: the relative importance of low
      habitual energy expenditure and cardiorespiratory fitness.
AB  - Glucose intolerance and diabetes mellitus are associated with physical
      inactivity, but it is unclear whether preventive interventions should aim at
      increasing overall energy expenditure or increasing participation in vigorous,
      fitness-enhancing activities. Studies aimed at separating and quantifying the
      effects of these two dimensions of physical activity should use well-validated
      measurement instruments and employ a study design in which the bivariate error
      structure of these instruments is determined. In the Isle of Ely Study
      (Cambridgeshire, United Kingdom), 775 individuals aged 45-70 years in 1994-1997
      completed a glucose tolerance test and assessment of 4-day physical activity
      level (total energy expenditure/basal metabolic rate) by heart rate monitoring, a
      technique that has been validated against doubly labeled water and whole-body
      calorimetry. Cardiorespiratory fitness (maximum oxygen uptake (VO2max) per kg))
      was measured in a submaximal test. To correct for measurement error, the authors
      had 190 individuals repeat both tests on three occasions at 4-month intervals.
      Two-hour glucose level was negatively correlated with physical activity level
      (men: r = -0.22, p < 0.001; women: r = -0.11, p < 0.05) and VO2max per kg (men: r
      = -0.18, p < 0.01; women: r = -0.19, p < 0.001) and was positively correlated
      with age and obesity. The model incorporating bivariate adjustment for
      measurement error showed that energy expenditure had a major effect on glucose
      tolerance, but there was less of an effect for cardiorespiratory fitness. These
      data provide support for public health strategies aimed at increasing overall
      energy expenditure.

PMID- 10909951
TI  - Total homocysteine and estrogen status indicators in the Third National Health
      and Nutrition Examination Survey.
AB  - The possibility that estrogen status modulates total homocysteine concentration,
      a risk factor for vascular occlusion, was examined in a representative sample of
      the US population, the Third National Health and Nutrition Examination Survey
      (phase 2), 1991-1994. The geometric mean serum total homocysteine concentration
      was compared among population subgroups differing on inferred estrogen status,
      after adjusting for potential confounding by age, race-ethnicity, smoking, and
      the serum concentration of creatinine, folate, and vitamin B-12. Premenopausal
      women aged 17-54 years had a lower mean serum total homocysteine concentration
      (8.1 micromol/liter, 95% confidence interval (CI): 7.9, 8.2) than men in the same
      age range (8.9 micromol/liter, 95% CI: 8.6, 9.3). In the age range 17-44 years,
      pregnant women (6.0 micromol/liter, 95% CI: 5.4, 6.8), but not oral contraceptive
      users (7.9 micromol/liter, 95% CI: 7.6, 8.2), had a lower mean serum total
      homocysteine concentration than nonpregnant, non-oral-contraceptive-using women
      (8.1 micromol/liter, 95% CI: 7.9, 8.2). The mean serum total homocysteine
      concentration of estrogen-using women aged > or = 55 years (9.5 micromol/liter,
      95% CI: 8.9, 10.1) was significantly decreased relative to nonestrogen users
      (10.7 micromol/liter, 95% CI: 10.3, 11.1) and men (10.4 micromol/liter, 95% CI:
      9.8, 11.0) in the same age range. These findings suggest that higher estrogen
      status is associated with a decreased mean serum total homocysteine
      concentration, independent of nutritional status and muscle mass, and that
      estrogen may explain the previously reported male-female difference in total
      homocysteine concentration.

PMID- 10909952
TI  - Multivitamin use and mortality in a large prospective study.
AB  - To determine the relation between multivitamin use and death from heart disease,
      cerebrovascular disease, and cancer, the authors examined a prospective cohort of
      1,063,023 adult Americans in 1982-1989 and compared the mortality of users of
      multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C,
      or E in combination with that of vitamin nonusers by using multivariate Cox
      proportional hazard models. Multivitamin users had heart disease and
      cerebrovascular disease mortality risks similar to those of nonusers, whereas
      combination users had mortality risks that were 15% lower than those of nonusers.
      Multivitamin and combination use had minimal effect on cancer mortality overall,
      although mortality from all cancers combined was increased among male current
      smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence
      interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16,
      95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR =
      0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked.
      No such associations were seen in women. These observational data provide limited
      support for the hypothesis that multivitamin use in combination with vitamin A,
      C, or E may reduce heart disease and cardiovascular disease mortality, but add to
      concerns raised by randomized studies that some vitamin supplements may adversely
      affect male smokers.

PMID- 10909953
TI  - Are the obese at greater risk for depression?
AB  - Two waves of data from a community-based study (Alameda County Study, 1994-1995)
      were used to investigate the association between obesity and depression.
      Depression was measured with 12 items covering Diagnostic and Statistical Manual
      of Mental Disorders: DSM-IV diagnostic criteria for major depressive episode.
      Following US Public Health Service criteria, obese subjects were defined as those
      with body mass index scores at the 85th percentile or higher. Covariates were
      age, sex, education, marital status, social isolation and social support, chronic
      medical conditions, functional impairment, life events, and financial strain.
      Results were mixed. In cross-sectional analyses, greater odds for depression in
      1994 were observed for the obese, with and without adjustment for covariates.
      When obesity and depression were examined prospectively, controlling for other
      variables, obesity in 1994 predicted depression in 1995 (odds ratio (OR) = 1.73,
      95% confidence interval (CI): 1.04, 2.87). When the data were analyzed with
      obesity defined as a body mass index of > or = 30, cross-sectional results were
      the same. However, the prospective multivariate analyses were not significant (OR
      = 1.43, 95% CI: 0.85, 2.43). Although these data do not resolve the role of
      obesity as a risk factor for depression, overall the results suggest an
      association between obesity and depression. The authors found no support for the
      "jolly fat" hypothesis (obesity reduces risk of depression). However, there has
      been sufficient disparity of results thus far to justify continued research.

PMID- 10909954
TI  - How many foodborne outbreaks of Salmonella infection occurred in France in 1995?
      Application of the capture-recapture method to three surveillance systems.
AB  - Despite control measures, foodborne outbreaks of non-typhi Salmonella infection
      continue to occur in developed countries. The authors aimed to assess the number
      of foodborne Salmonella outbreaks that occurred in France in 1995 using a capture
      recapture approach. Data from three sources--the National Public Health Network
      (NPHN), the Ministry of Agriculture (MA), which receives mandatory notification,
      and the National Salmonella and Shigella Reference Center (NRC)-were collected.
      Matching algorithms permitted identification of matched outbreaks. The total
      number of outbreaks was estimated by log-linear modeling taking into account
      source dependencies and the variable catchability. The final estimate was
      adjusted for the positive predictive value (66%) of the NRC case definition. The
      dependence between the NPHN and the MA was also evaluated by means of a
      qualitative survey. A total of 716 foodborne Salmonella outbreaks were reported
      to the three sources, and 108 matches were identified. The best-fitting model,
      taking into account a positive dependence between the NPHN and MA sources, gave
      an estimate of 757 outbreaks. The sensitivity was 15% for the NPHN, 10% for the
      MA, and 50% for the NRC. In France, routine mandatory reporting of foodborne
      Salmonella outbreaks is very incomplete, and it is not representative of the
      serotype and the type of outbreak.

PMID- 10909955
TI  - Impact of protease inhibitors and other antiretroviral treatments on acquired
      immunodeficiency syndrome survival in San Francisco, California, 1987-1996.
AB  - The authors assessed temporal trends in acquired immunodeficiency syndrome (AIDS)
      survival for 15,271 persons in San Francisco, California, diagnosed between 1987
      and 1996 with an opportunistic illness included in the 1987 AIDS case definition.
      Predictors of survival were evaluated for 5,686 persons who were diagnosed
      between 1993 and 1996 and met the 1993 AIDS case definition. Median survival was
      19 months for persons diagnosed between 1987 and 1989, 17 months for persons
      diagnosed between 1990 and 1992, 15 months for persons diagnosed between 1993 and
      1994, and 31 months for persons diagnosed between 1995 and 1996. Decreased
      mortality was associated with use of antiretroviral therapy without protease
      inhibitors before AIDS (relative hazard (RH) = 0.88, 95% confidence interval
      (CI): 0.8, 1.0) and after AIDS (RH = 0.83, 95% CI: 0.7, 0.9) and use of
      antiretroviral agents with protease inhibitors before AIDS (RH = 0.25, 95% CI:
      0.2, 0.3) and after AIDS (RH = 0.36, 95% CI: 0.3, 0.4). Increased mortality was
      found for persons aged > or = 40 years (RH = 1.43, 95% CI: 1.3, 1.6), persons
      initially diagnosed with an opportunistic illness (RH = 1.97, 95% CI: 1.8, 2.2),
      and homosexual injection drug users (RH = 1.33, 95% CI: 1.2, 1.5). Survival after
      AIDS has increased. Treatment with antiretroviral agents, particularly protease
      inhibitors, strongly predicts improved survival.

PMID- 10909956
TI  - Multiple modes of hepatitis A virus transmission among methamphetamine users.
AB  - Methamphetamine users are at increased risk of hepatitis A, but modes of
      transmission are unclear. The authors conducted a case-control study among
      methamphetamine users during an outbreak in Iowa in 1997. Twenty-eight reported,
      laboratory-confirmed, hepatitis A cases did not differ from 18 susceptible
      controls with respect to age, sex, or number of doses used. When compared with
      controls in multivariate analysis, case-patients were more likely to have
      injected methamphetamine (odds ratio (OR) = 5.5, 95% confidence interval (CI):
      1.1, 27), to have used methamphetamine with another case-patient (OR = 6.2, 95%
      CI: 0.95, 41), and to have used brown methamphetamine (OR = 5.5, 95% CI: 0.51,
      59). Receptive needle sharing was reported by 10 of the 20 case-patients who
      injected. Methamphetamine use with another case-patient was also associated with
      hepatitis A in an analysis restricted to noninjectors (OR = 17, 95% CI: 1.0,
      630). During this outbreak, hepatitis A may have been transmitted from person to
      person among methamphetamine users through the fecal-oral and the percutaneous
      routes. Methamphetamine users should be vaccinated against hepatitis A and should
      be given immune globulin if they used methamphetamine with a case-patient in the
      last 2 weeks. Persons who intend to continue using methamphetamine should be
      advised about safer practices.

PMID- 10909957
TI  - Re: "Interaction between tobacco and alcohol consumption and the risk of cancers
      of the upper aero-digestive tract in Brazil".

PMID- 10909958
TI  - Re: "Parallel analyses of individual and ecologic data on residential radon,
      cofactors, and lung cancer in Sweden".

PMID- 10909959
TI  - Re: "Placenta previa: preponderance of male sex at birth".

PMID- 10909960
TI  - Melanin-concentrating hormone regulates leptin synthesis and secretion in rat
      adipocytes.
AB  - Obesity is a common problem in Western society and is associated with significant
      morbidity and mortality. Energy homeostasis is regulated by a complex system
      involving both peripheral signals such as leptin and a number of orexigenic and
      anorectic neuropeptides. Obesity can result from dysregulation of the peripheral
      and/or central signals. Melanin-concentrating hormone (MCH) is a hypothalamic
      peptide that is important in the regulation of feeding behavior, primarily via
      uncharacterized signaling pathways in the central nervous system. Leptin,
      expressed in adipose tissue, mediates some of its actions through several
      hypothalamic neuropeptides, notably agouti-related peptide, proopiomelanocortin,
      and neuropeptide Y. Expression of leptin is regulated by dietary status, insulin,
      and glucocorticoids. Furthermore, certain neuropeptides may act on adipocytes.
      However, the potential effect of MCH has not been investigated. We report that
      MCH stimulates leptin mRNA expression and leptin secretion. MCH stimulated a 2
      fold increase in leptin secretion by isolated rat adipocytes after 4 h of
      treatment. This increase in secreted leptin was preceded by a rapid and transient
      increase in ob mRNA levels; MCH stimulated a 2.5-fold increase in ob mRNA within
      1 h of treatment, followed by a decline to basal levels within 4 h. In addition,
      we demonstrate that the MCH receptor SLC-1 is expressed in adipocytes, suggesting
      that fat cells may be targets of MCH or an MCH-like peptide under physiological
      conditions. Finally, using a radioimmunoassay, MCH/MCH-like peptide was detected
      in rat plasma. This study establishes a novel in vitro mammalian system for
      examining MCH signaling pathways.

PMID- 10909961
TI  - Fatty acid oxidation and the regulation of malonyl-CoA in human muscle.
AB  - Questions concerning whether malonyl-CoA is regulated in human muscle and whether
      malonyl-CoA modulates fatty acid oxidation are still unanswered. To address these
      questions, whole-body fatty acid oxidation and the concentration of malonyl-CoA,
      citrate, and malate were determined in the vastus lateralis muscle of 16 healthy
      nonobese Swedish men during a sequential euglycemic-hyperinsulinemic clamp.
      Insulin was infused at rates of 0.25 and 1.0 mU x kg(-1) x min(-1), and glucose
      was infused at rates of 2.0 +/- 0.2 and 8.1 +/- 0.7 mg x kg(-1) x min(-1),
      respectively. During the low-dose insulin infusion, whole-body fatty acid
      oxidation, as determined by indirect calorimetry, decreased by 22% from a basal
      rate of 0.94 +/- 0.06 to 0.74 +/- 0.07 mg x kg(-1) x min(-1) (P = 0.005), but no
      increase in malonyl-CoA was observed. In contrast, during the high-dose insulin
      infusion, malonyl-CoA increased from 0.20 +/- 0.01 to 0.24 +/- 0.01 nmol/g (P <
      0.001), and whole-body fatty acid oxidation decreased by an additional 41% to
      0.44 +/- 0.06 mg x kg(-1) x min(-1) (P < 0.001). The increase in malonyl-CoA was
      associated with 30-50% increases in the concentrations of citrate (102 +/- 6 vs.
      137 +/- 7 nmol/g, P < 0.001), an allosteric activator of the rate-limiting enzyme
      in the malonyl-CoA formation, acetyl-CoA carboxylase, and malate (80 +/- 6 vs.
      126 +/- 9 nmol/g, P = 0.002), an antiporter for citrate efflux from the
      mitochondria. Significant correlations were observed between the concentration of
      malonyl-CoA and both glucose utilization (r = 0.53, P = 0.002) and the sum of the
      concentrations of citrate and malate (r = 0.52, P < 0.001), a proposed index of
      the cytosolic concentration of citrate. In addition, an inverse correlation
      between malonyl-CoA concentration and fatty acid oxidation was observed (r = 
      0.32, P = 0.03). The results indicate that an infusion of insulin and glucose at
      a high rate leads to increases in the concentration of malonyl-CoA in skeletal
      muscle and to decreases in whole-body and, presumably, muscle fatty acid
      oxidation. Furthermore, they suggest that the increase in malonyl-CoA in this
      situation is due, at least in part, to an increase in the cytosolic concentration
      of citrate. Because cytosolic citrate is also an inhibitor of
      phosphofructokinase, an attractive hypothesis is that changes in its
      concentration are part of an autoregulatory mechanism by which glucose modulates
      its own use and the use of fatty acids as fuels for skeletal muscle.

PMID- 10909963
TI  - Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of
      exercise training.
AB  - The fiber type-specific expression of skeletal muscle GLUT4 and the effect of 2
      weeks of low-intensity training were investigated in 8 young untrained male
      subjects. Single muscle fibers were dissected from a vastus lateralis biopsy
      sample. Based on myosin heavy chain (MHC) expression, fibers were pooled into 3
      groups (MHC I, MHC IIA, and MHC IIX), and the GLUT4 content of 15-40 pooled
      fibers was determined using SDS-PAGE and immunological detection. The GLUT4
      content in pooled muscle fibers expressing MHC I was approximately 20% higher (P
      < 0.05) than that in muscle fibers expressing MHC IIA or MHC IIX. No difference
      in GLUT4 could be detected between fibers expressing MHC IIA or MHC IIX. Two
      weeks of exercise training increased (P < 0.05) the peak power output of the knee
      extensors by 13%, the maximal activities of citrate synthase and 3-hydroxyacyl
      CoA dehydrogenase by 21 and 18%, respectively, and the GLUT4 protein content by
      26% in a muscle homogenate. Furthermore, a 23% increase (P < 0.05) in GLUT4 was
      seen in fibers expressing the MHC I isoform after exercise training for 2 weeks.
      No change was seen in fibers expressing MHC IIA or MHC IIX. In conclusion, our
      data directly demonstrate that GLUT4 is expressed in a fiber type-specific manner
      in human skeletal muscle, although fiber type differences are relatively small.
      In addition, low-intensity exercise training recruiting primarily fibers
      expressing MHC I increased GLUT4 content in these fibers but not in fibers
      expressing MHC IIA or MHC IIX, indicating that GLUT4 protein content is related
      more to activity level of the fiber than to its fiber type, which is defined by
      expression of contractile protein.

PMID- 10909962
TI  - Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated
      glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O,
      [18F]fluoro-deoxy-glucose, and positron emission tomography.
AB  - In vitro studies have shown that insulin and exercise stimulate glucose uptake in
      part via distinct mechanisms. We determined whether a high rate of insulin
      stimulated glucose uptake (good insulin sensitivity) is associated with an
      enhanced ability of exercise to increase glucose uptake in vivo in humans. In our
      study, 22 normal subjects performed one-legged isometric exercise for 105 min (45
      150 min) under intravenously maintained euglycemic-hyperinsulinemic conditions (0
      150 min). Rates of oxygen consumption, blood flow, and glucose uptake were
      quantitated simultaneously in skeletal muscle of both legs using [15O]O2,
      [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one
      legged exercise, performed at an intensity of 11% of maximal isometric force, was
      designed to induce similar increases in oxygen consumption in both groups. In the
      entire group, exercise increased oxygen consumption from 2.3 +/- 0.3 ml x kg(-1)
      muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin
      and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1)
      muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x min(-1)
      (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose
      uptake was due to marked increases in blood flow (36 +/- 5 ml x kg(-1) muscle x
      min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x min(-1) [insulin and
      exercise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/
      0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/1 (insulin and exercise) (P < 0.001).
      The subjects were classified according to their mean rate of whole-body insulin
      stimulated glucose uptake into those with high (49 +/- 3 micromol x kg(-1) x min(
      1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated
      glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1)
      muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin
      stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x min(-1)) rates of oxygen
      consumption were comparable between the groups. Exercise increased glucose uptake
      more in the group with high insulin sensitivity (195 +/- 25 pmol x kg(-1) muscle
      x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol
      x kg(-1) muscle x min(-1)) (P < 0.05). Muscle blood flow was closely correlated
      with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin
      stimulated (30 +/- 5 vs. 35 +/- 6 ml x kg(-1) muscle x min(-1)) and exercise
      induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x min(-1)) in
      muscle blood flow were similar between the groups. Glucose extraction remained
      higher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in
      the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05). We
      conclude that whereas acute exercise per se increases glucose uptake via
      increasing glucose delivery, good insulin sensitivity modulates exercise-induced
      increases in glucose uptake by enhancing cellular glucose extraction.

PMID- 10909964
TI  - Glycogen synthase sensitivity to insulin and glucose-6-phosphate is mediated by
      both NH2- and COOH-terminal phosphorylation sites.
AB  - In skeletal muscle, insulin activates glycogen synthase by reducing
      phosphorylation at both NH2- and COOH-terminal sites of the enzyme and by
      elevating the levels of glucose-6-phosphate, an allosteric activator of glycogen
      synthase. To study the mechanism of regulation of glycogen synthase by insulin
      and glucose-6-phosphate, we generated stable Rat-1 fibroblast clones expressing
      rabbit muscle glycogen synthase with Ser-->Ala substitutions at key
      phosphorylation sites. We found that 1) elimination of the phosphorylation of
      either NH2- or COOH-terminal sites did not abolish insulin stimulation of
      glycogen synthase; 2) mutations at both Ser-7 and Ser-640 were necessary to
      bypass insulin activation; 3) mutation at Ser-7, coupled with the disruption of
      the motif for recognition by glycogen synthase kinase-3 (GSK-3), did not
      eliminate the insulin effect; and 4) mutation of either Ser-7 or Ser-640
      increased the sensitivity of glycogen synthase to glucose 6-phosphate >10-fold.
      We conclude that Ser-7 and Ser-640 are both involved in mediating the response of
      glycogen synthase to insulin and activation by glucose 6-phosphate. In Rat-1
      fibroblasts, GSK-3 action is not essential for glycogen synthase activation by
      insulin, and GSK-3-independent mechanisms also operate.

PMID- 10909965
TI  - Involvement of thyroid hormones in the effect of intracerebroventricular leptin
      infusion on uncoupling protein-3 expression in rat muscle.
AB  - We have shown previously that continuous (6 days) intracerebroventricular (ICV)
      leptin infusion in normal rats resulted in decreases in food intake and body
      weight. A reduction of food intake imposed on control rats (pair-feeding), aimed
      at mimicking leptin-induced hyperphagia, produced a marked decrease in the
      expression of muscle uncoupling protein-3 (UCP-3), whereas ICV infusion of leptin
      prevented such a decrease in UCP-3. To investigate an involvement of thyroid
      hormones in this effect of leptin, plasma levels of these hormones were
      determined in ICV leptin-infused, ICV vehicle-infused ad libitum fed or pair-fed
      controls. ICV leptin infusion and pair-feeding resulted in decreased plasma
      thyroid-stimulating hormone (TSH) and T4 levels relative to ad libitum fed
      controls. ICV leptin infusion maintained plasma levels of T3, but the levels were
      decreased by pair-feeding. The activity of the enzyme (hepatic 5'-monodeiodinase)
      responsible for T4/T3 conversion was measured. In the leptin-infused group, the
      activity of 5'-monodeiodinase was maintained at the values measured in ad libitum
      fed rats; in pair-fed rats, activity was reduced. Thus, conversion of T4 to T3 is
      decreased by pair-feeding, whereas such is not the case during leptin infusion.
      To further substantiate an involvement of thyroid hormones in the effect of
      leptin on muscle UCP-3 expression, hypothyroid rats were ICV infused with leptin
      or vehicle. It was observed that in hypothyroid rats, ICV leptin was unable to
      maintain muscle UCP-3 expression at values measured in ad libitum fed controls.
      These results suggest that central leptin stimulates T3 production via an
      activation of T4 to T3 conversion, and that this stimulation could be responsible
      for the effect of leptin on muscle UCP-3 expression. Thyroid hormones could thus
      be important mediators of the effect of leptin on energy expenditure.

PMID- 10909966
TI  - Aberrant macrophage cytokine production is a conserved feature among autoimmune
      prone mouse strains: elevated interleukin (IL)-12 and an imbalance in tumor
      necrosis factor-alpha and IL-10 define a unique cytokine profile in macrophages
      from young nonobese diabetic mice.
AB  - Cytokines derived from macrophages (Mo) play a critical role in the development
      of type 1 diabetes in the nonobese diabetic (NOD) mouse. Based on earlier
      findings from lupus-prone strains of inherent cytokine defects in Mo , NOD Mo
      were evaluated for intrinsically dysregulated cytokine production with the
      potential to initiate or exacerbate disease. Endotoxin-activated peritoneal Mo
      from young prediseased NOD mice produced interleukin (IL)-1 and tumor necrosis
      factor (TNF)-alpha levels similar to those of Mo from a panel of control strains
      but reduced compared with the congenic diabetes-resistant NOR strain. IL-6 and IL
      10 production were similar in NOD and NOR Mo, indicating that reduction in NOD IL
      1 and TNF-alpha expression was selective. Nevertheless, the ratio of TNF-alpha
      and IL-10 production, a stringent index of normal Mo function, distinguished NOD
      from all normal strains. The most striking feature of NOD Mo, however, was their
      substantially elevated IL-12 production. This response was induced not only by
      endotoxin but also by bacillus Calmette-Guerin (BCG) and CD40 ligand and was
      associated with (and likely caused by) the enhanced and prolonged expression of
      p40 mRNA. Moreover, NOD Mo IL-12 expression appeared to be near maximally induced
      by lipopolysaccharide (LPS) alone, because it was only slightly enhanced by the
      addition of gamma-interferon, a stimulus that substantially elevated LPS-induced
      IL-12 production in Mo from normal strains. Accompanied by a unique profile of
      TNF-alpha and IL-10, the dramatic elevation of IL-12 expression by NOD Mo
      reflects intrinsic defects of the innate immune system with the potential to
      initiate and propagate the pathogenic autoreactive T-helper type 1 response
      characteristic of type 1 diabetes.

PMID- 10909967
TI  - Cytokines induce apoptosis in beta-cells isolated from mice lacking the inducible
      isoform of nitric oxide synthase (iNOS-/-).
AB  - Prolonged exposure of rodent beta-cells to combinations of cytokines induces the
      inducible form of nitric oxide synthase (iNOS) expression and Fas expression,
      nitric oxide (NO) production, and cell death. It also induces the expression of
      potential "defense" genes, such as manganese superoxide dismutase (MnSOD) and
      heat shock protein (hsp) 70. NO is a radical with multifaceted actions. Recent
      studies have shown that NO, in addition to having cytotoxic actions, may regulate
      gene transcription. It remains unclear whether NO mediates cytokine-induced gene
      expression and subsequent beta-cell death. Previous studies using NO synthase
      blockers yielded conflicting results, which may be due to nonspecific effects of
      these agents. In this study, we examined the effects of cytokines on gene
      expression, determined by reverse transcriptase-polymerase chain reaction (RT
      PCR), and viability, determined by nuclear dyes, of pancreatic islets or
      fluorescence-activated cell sorter (FACS)-purified beta-cells isolated from iNOS
      knockout mice (iNOS-/-, background C57BL/6x129SvEv) or their respective controls
      (C57BL/6x129SvEv). The combination of cytokines used was interleukin-1beta (50
      U/ml) plus gamma-interferon (1,000 U/ml) plus tumor necrosis factor-alpha (1,000
      U/ml). The lack of cytokine-induced iNOS activity in the iNOS-/- islet cells was
      confirmed by RT-PCR and nitrite determination. Cytokines induced a >3-fold
      increase in Fas and MnSOD mRNA expression in wild-type (WT) and iNOS-/- islets.
      On the other hand, hsp 70 was induced in WT but not in iNOS-/- islets. Prolonged
      (6-9 days) exposure of WT islets to cytokines leads to an 80-90% decrease in
      islet cell viability, whereas viability decreased by only 10-30% in iNOS-/- islet
      cells. To determine the mode of cytokine-induced cell death, FACS-purified beta
      cells were exposed to the same cytokines. After 9 days, the apoptosis index was
      similarly increased in WT (39 +/- 3%) and iNOS4-/- (33 +/- 4%) beta-cells. On the
      other hand, cytokines increased necrosis in WT (20 +/- 4%) but not in iNOS-/- (7
      +/- 3%) beta-cells. From these data, we concluded that 1) NO is required for
      cytokine-induced hsp 70 mRNA expression but not for Fas and MnSOD expression, 2)
      cytokines induce both apoptosis and necrosis in mouse beta-cells, and 3) cytokine
      induced apoptosis is mostly NO-independent, whereas necrosis requires NO
      formation.

PMID- 10909968
TI  - Protection of insulin-producing RINm5F cells against cytokine-mediated toxicity
      through overexpression of antioxidant enzymes.
AB  - Nitric oxide (NO) and reactive oxygen species (ROS) are crucial elements in
      cytokine-mediated beta-cell destruction. In insulin-producing RINm5F cells,
      overexpression of cytoprotective enzymes provides significant protection against
      the synergistic toxicity of NO and ROS. We therefore examined whether
      overexpression of catalase (Cat), glutathione peroxidase (Gpx), and Cu/Zn
      superoxide dismutase (SOD) can provide protection for bioengineered RINm5F cells
      against cytokine-mediated toxicity. A 72-h exposure of RINm5F control cells to
      interleukin-1beta (IL-1beta) alone or a combination of IL-1beta, tumor necrosis
      factor-alpha, and gamma-interferon resulted in a time- and concentration
      dependent decrease of cell viability in the 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyl tetrazolium bromide (MTT) cytotoxicity assay. Although IL-1beta alone
      caused only a moderate reduction of viability in the range of 25%, the cytokine
      mixture induced a significant loss of viability of >75%. This increased toxicity
      of the cytokine mixture compared with that of IL-1beta alone could be explained
      by a higher rate of NO generation within the early 24-48 h incubation period that
      would favor the toxic synergism of NO and oxygen free radicals. Overexpression of
      Cat, Gpx, and Cu/Zn SOD protected against toxicity of the cytokine mixture but
      not against that of IL-1beta alone. The reduction of cytokine-mediated toxicity
      was evident also because of an increased proliferation rate and a drastic
      decrease in the cell death rate. The improved antioxidant defense status did not
      prevent the activation of iNOS after cytokine exposure. However, RINm5F cells
      overexpressing cytoprotective enzymes showed a significantly lower level of ROS
      damaged protein residues. Thus, protection through Cat, Gpx, and Cu/Zn SOD
      overexpression was apparently because of an inactivation of ROS generated in the
      signal cascades of the cytokines. Overexpression of cytoprotective enzymes thus
      represents a feasible strategy to protect insulin-producing cells against
      cytokine-mediated cytotoxicity.

PMID- 10909969
TI  - K(ATP) channel openers protect rat islets against the toxic effect of
      streptozotocin.
AB  - We examined the influence of two K(ATP) channel openers, diazoxide and an analog
      (NNC 55-0118), on experimental beta-cell damage induced by streptozotocin (STZ;
      0.5 mmol/l). Rat pancreatic islets were exposed to diazoxide or NNC 55-0118 for
      30 min and were further incubated for 30 min after the addition of STZ. The
      islets were then washed and cultured for 24 h. Islets exposed to STZ alone showed
      extensive morphological damage, reduced glucose oxidation, low insulin content,
      and severely impaired glucose-stimulated insulin secretion and proinsulin
      biosynthesis. Islets treated with STZ in the presence of the channel openers
      (0.03-0.30 mmol/l) showed dose-dependent preservation of the morphology and
      improved glucose oxidation rates, insulin content, and secretion. NNC 55-0118 was
      capable of fully counteracting the STZ impairment, whereas diazoxide had a less
      protective effect. NNC 55-0118 did not counteract STZ-induced depression of islet
      NAD levels when examined 2 h after STZ exposure, which suggests that the
      mechanism of action by NNC 55-0118 is not through an inhibition of poly(ADP
      ribose) polymerase. The results illustrate that K(ATP) channel openers can
      protect insulin-producing cells against toxic damage, an effect that may be of
      use in subjects with ongoing insulitis.

PMID- 10909970
TI  - Regulation of the diabetes-associated autoantigen IA-2 in INS-1 pancreatic beta
      cells.
AB  - IA-2, a member of the protein tyrosine phosphatase family, represents a major
      target autoantigen in type 1 diabetes. To study the regulation of IA-2 gene
      expression, we used INS-1 insulinoma cells to analyze beta-cell signal
      transduction pathways as well as the effect of metabolic and hormonal factors
      involved in the regulation of the insulin secretory pathway. Quantitative
      competitive reverse transcriptase-polymerase chain reaction revealed that an
      increase of cellular cAMP mediated by forskolin (10 micromol/l, 24 h) or 3
      isobutyl-1-methylxanthine (100 micromol/l, 24 h) induced maximal stimulation of
      IA-2 mRNA levels (451 +/- 85 and 338 +/- 86% compared with basal conditions; P <
      0.001). In contrast, activation of protein kinase C (PKC) by short-term treatment
      with phorbol 12-myristate 13-acetate (PMA) (1 micromol/l, 6 h) did not alter IA-2
      expression, whereas depletion of PKC by prolonged culturing (24 h) exerted a
      significant inhibition (57 +/- 24%; P < 0.05). cAMP-dependent upregulation was
      confirmed by the findings that glucagon (10 micromol/l, 24-48 h) increased levels
      of IA-2 mRNA (190 +/- 35%; P < 0.05), whereas short-term incubation with high
      glucose concentration showed no effect. However, prolonged incubation in high
      glucose (21 mmol/l) induced a time- and dose-dependent increase of IA-2 mRNA
      expression, reaching maximal values after 144 h (285 +/- 68%; P < 0.05). These
      studies demonstrate that stimuli of insulin secretion that operate by activation
      of adenylate cyclase generating cAMP significantly increase IA-2 gene expression.
      In contrast, activation of PKC by high glucose concentration or PMA exerted no
      effect, suggesting that IA-2 gene expression is not simply coupled to insulin
      secretion, but may be involved in the fine regulation of beta-cell function.
      These findings may be important to clarify the function of IA-2 in beta-cells and
      elucidate mechanisms involved in the induction of autoimmunity to IA-2.

PMID- 10909971
TI  - Activating transcription factor-2 is a positive regulator in CaM kinase IV
      induced human insulin gene expression.
AB  - Insulin plays a crucial role in the regulation of glucose-homeostasis, and its
      synthesis is regulated by several stimuli. The transcription of the human insulin
      gene, enhanced by an elevated intracellular concentration of calcium ions, was
      completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The
      activity of the transcription factor activating transcription factor-2 (ATF-2),
      which binds to the cAMP responsive elements of the human insulin gene, was
      enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis
      studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for
      activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not
      altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen
      activated protein (MAP) kinase. Furthermore, when transfected into rat primary
      cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity,
      whereas cAMP response element-binding protein (CREB) repressed it. These results
      suggest a mechanism in which ATF-2 regulates insulin gene expression in
      pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased
      by an elevated concentration of calcium ions.

PMID- 10909972
TI  - Acute overexpression of lactate dehydrogenase-A perturbs beta-cell mitochondrial
      metabolism and insulin secretion.
AB  - Islet beta-cells express low levels of lactate dehydrogenase and have high
      glycerol phosphate dehydrogenase activity. To determine whether this
      configuration favors oxidative glucose metabolism via mitochondria in the beta
      cell and is important for beta-cell metabolic signal transduction, we have
      determined the effects on glucose metabolism and insulin secretion of acute
      overexpression of the skeletal muscle isoform of lactate dehydrogenase (LDH)-A.
      Monitored in single MIN6 beta-cells, LDH hyperexpression (achieved by
      intranuclear cDNA microinjection or adenoviral infection) diminished the response
      to glucose of both phases of increases in mitochondrial NAD(P)H, as well as
      increases in mitochondrial membrane potential, cytosolic free ATP, and cystolic
      free Ca2+. These effects were observed at all glucose concentrations, but were
      most pronounced at submaximal glucose levels. Correspondingly, adenoviral vector
      mediated LDH-A overexpression reduced insulin secretion stimulated by 11 mmol/l
      glucose and the subsequent response to stimulation with 30 mmol/l glucose, but it
      was without significant effect when the concentration of glucose was raised
      acutely from 3 to 30 mmol/l. Thus, overexpression of LDH activity interferes with
      normal glucose metabolism and insulin secretion in the islet beta-cell type, and
      it may therefore be directly responsible for insulin secretory defects in some
      forms of type 2 diabetes. The results also reinforce the view that glucose
      derived pyruvate metabolism in the mitochondrion is critical for glucose
      stimulated insulin secretion in the beta-cell.

PMID- 10909974
TI  - Induction of PEPCK gene expression in insulinopenia in rat small intestine.
AB  - PEPCK is a key enzyme of gluconeogenesis in liver and kidney. Recently, we have
      shown that small intestine also contributes to the endogenous glucose production
      in insulinopenia in rats and that glutamine is the main precursor of glucose
      synthesized in this tissue. The expression of the PEPCK gene in rat and human
      small intestine and the effect of streptozotocin-induced diabetes and fasting
      have been studied using reverse transcriptase-polymerase chain reaction, Northern
      blot analysis, and determination of enzyme activity. The PEPCK gene is expressed
      along the whole small intestine in adult rat and human. The abundance of PEPCK
      mRNA was increased approximately 30 times in the duodenum, 15 times in the
      jejunum, and only 3 times in the ileum from diabetic rats. PEPCK mRNA was
      downregulated in all parts of the tissue upon insulin treatment for 10 h. In 48-h
      fasted rats, the PEPCK mRNA abundance was increased 17 times in the duodenum and
      the jejunum and 3 times in the ileum, and it was normalized upon refeeding for 7
      h. PEPCK activity was also increased 2-5 times in diabetic and fasted rats in the
      duodenum and jejunum but not in the ileum. We conclude that PEPCK is a crucial
      enzyme contributing to the induction of gluconeogenesis in small intestine, just
      as it is well known to be in the liver and kidney.

PMID- 10909973
TI  - Glucagon-like peptide 1 stimulates insulin gene promoter activity by protein
      kinase A-independent activation of the rat insulin I gene cAMP response element.
AB  - Glucagon-like peptide 1 (GLP-1), a hormonal activator of adenyl cyclase,
      stimulates insulin gene transcription, an effect mediated by the cAMP response
      element (CRE) of the rat insulin I gene promoter (RIP1). Here we demonstrate that
      the signaling mechanism underlying stimulatory effects of GLP-1 on insulin gene
      transcription results from protein kinase A (PKA)-independent activation of the
      RIP1 CRE. Although GLP-1 stimulates cAMP production in rat INS-1 insulinoma
      cells, we find accompanying activation of a -410-bp RIP1 luciferase construct (
      410RIP1-LUC) to exist independently of this second messenger. GLP-1 produced a
      dose-dependent stimulation of -410RIP1-LUC (EC50 0.43 nmol/l), an effect
      reproduced by the GLP-1 receptor agonist exendin-4 and abolished by the
      antagonist exendin(9-39). Activation of RIP1 by GLP-1 was not affected by
      cotransfection with dominant-negative Gs alpha, was not blocked by cAMP
      antagonist Rp-cAMPS, and was insensitive to PKA antagonist H-89. Truncation of 
      410RIP1-LUC to generate -307-, -206-, and -166-bp constructs revealed 2 segments
      of RIP1 targeted by GLP-1. The first segment, not regulated by forskolin, was
      located between -410 and -307 bp of the promoter. The second segment, regulated
      by both GLP-1 and forskolin, included the CRE and was located between -206 and 
      166 bp. Consistent with these observations, stimulatory effects of GLP-1 at RIP1
      were reduced after introduction of delta-182 and delta-183/180 inactivating
      deletions at the CRE. The action of GLP-1 at -410RIP1-LUC was also reduced by
      cotransfection with A-CREB, a genetically engineered isoform of the CRE binding
      protein CREB, which dimerizes with and prevents binding of basic-region-leucine
      zipper (bZIP) transcription factors to the CRE. In contrast, the action of GLP-1
      at the CRE was not blocked by cotransfection with M1-CREB, an isoform that lacks
      a consensus serine residue serving as substrate for PKA-mediated phosphorylation.
      On the basis of these studies, it is proposed that PKA-independent stimulatory
      actions of GLP-1 at RIP1 are mediated by bZIP transcription factors related in
      structure but not identical to CREB.

PMID- 10909975
TI  - Decreased insulin responsiveness of glucose uptake in cultured human skeletal
      muscle cells from insulin-resistant nondiabetic relatives of type 2 diabetic
      families.
AB  - To investigate the contribution of inherited biochemical defects to the
      peripheral insulin resistance of type 2 diabetes, we studied cultured skeletal
      muscle from 10 insulin-resistant nondiabetic first-degree relatives of type 2
      diabetic families and 6 control subjects. Insulin stimulation of glucose uptake
      and glycogen synthesis was maximal in myoblasts. Insulin-stimulated glucose
      uptake (fold-stimulation over basal uptake) was decreased in relative compared
      with control myoblasts at 0.001 micromol/l (0.93 +/- 0.05 [mean +/- SE] vs. 1.15
      +/- 0.06, P < 0.05) and 0.1 micromol/l (1.38 +/- 0.10 vs. 1.69 +/- 0.08, P =
      0.025) insulin. Insulin responsiveness was markedly impaired in 5 of the relative
      myoblast cultures, and in 4 of these, there was an associated increase in basal
      glucose uptake (76.7 +/- 7.0 vs. 47.4 +/- 5.5 pmol x min(-1) x mg(-1) protein,
      relative vs. control; P < 0.02). Expression of insulin receptor substrate 1,
      phosphatidylinositol 3-kinase, protein kinase B, and glycogen synthase was normal
      in the relative cultures with impaired insulin responsiveness. Glycogen synthesis
      was also normal in the relative cultures. We conclude that the persistence of
      impaired insulin responsiveness in some of the relative cultures supports the
      role of inherited factors in the insulin resistance of type 2 diabetes and that
      the association with increased basal glucose uptake suggests that the 2
      abnormalities may be linked.

PMID- 10909976
TI  - Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic
      subjects.
AB  - It has previously been shown that Wortmannin, a phosphatidylinositol 3-kinase
      inhibitor, inhibits glucose transport activated by insulin but not by ischemia,
      suggesting the importance of an activating mechanism that bypasses the insulin
      signal. To evaluate the relevance of this insulin-independent pathway in insulin
      resistant subjects, the ability of ischemia to stimulate glucose uptake was
      investigated in 9 patients with type 2 diabetes and in 9 healthy control subjects
      (fasting glucose level 9.4 +/- 0.8 vs. 5.1 +/- 0.1 mmol/l, P < 0.001, in type 2
      diabetic patients and control subjects, respectively; fasting insulin level
      insulin 8.1 +/- 2.6 vs. 4.5 +/-0.7 mU/l, P < 0.05, respectively) matched for sex,
      age, and BMI. Arterial plasma and interstitial concentrations of glucose and
      lactate (measured by subcutaneous and muscle microdialysis) were recorded in the
      forearm before, during, and after ischemia induced locally for 20 min. During
      ischemia, the muscle interstitial glucose concentration decreased significantly
      from 7.7 +/- 0.6 to 5.4 +/- 0.4 mmol/l (P < 0.01) and from 4.4 +/- 0.3 to 3.6 +/-
      0.3 mmol/l (P < 0.05) in type 2 diabetic patients and control subjects,
      respectively. The arterial-interstitial (A-I) glucose concentration difference
      was 1.7 +/- 0.6 and 0.7 +/- 0.3 mmol/ at basal, and it increased significantly to
      3.5 +/- 0.7 (P < 0.01) and 1.4 +/-0.3 mmol/l (P < 0.05) during ischemia in each
      group, respectively. Interstitial lactate increased significantly during ischemia
      from 0.8 +/- 0.1 to 1.1 +/- 0.1 mmol/l (P < 0.05) and from 0.5 +/- 0.1 to 0.9 +/-
      0.2 mmol/l (P < 0.05), respectively. The A-I glucose concentration difference was
      abolished immediately postischemia and regained after approximately 15 min,
      whereas high interstitial lactate levels remained elevated throughout the study.
      Subcutaneous interstitial glucose concentrations remained unchanged during
      ischemia and postischemia in both groups, whereas the interstitial lactate
      concentration in adipose tissue increased during ischemia from 1.4 +/- 0.2 to 2.0
      +/- 0.2 mmol/l (P < 0.05) and from 1.1 +/- 0.1 to 1.8 +/- 0.3 mmol/l (P < 0.05)
      in type 2 diabetic patients and control subjects, respectively. Plasma glucose
      and lactate levels were unchanged in both groups during the study period. The
      results show that in muscle, but not in adipose tissue, glucose uptake is
      efficiently activated by ischemia in insulin-resistant type 2 diabetic subjects,
      suggesting the activation of a putative alternative pathway to the insulin signal
      in muscle cells.

PMID- 10909977
TI  - Renal substrate metabolism and gluconeogenesis during hypoglycemia in humans.
AB  - To examine the potential contribution of precursor substrates to renal
      gluconeogenesis during hypoglycemia, 14 healthy subjects had arterialized hand
      vein and renal vein (under fluoroscopy) catheterized after an overnight fast. Net
      renal balance of lactate, glycerol, alanine, and glutamine was determined
      simultaneously with systemic and renal glucose kinetics using arteriovenous
      concentration differences and 6-[2H2]glucose tracer dilution. Renal plasma flow
      was measured by para-aminohippurate clearance and was converted to blood flow
      using the mathematical value (1-hematocrit). Arterial and renal vein samples were
      obtained in the postabsorptive state and during a 180-min hyperinsulinemic period
      during either euglycemia or hypoglycemia. Insulin increased from 49 +/- 14 to 130
      +/- 25 pmol/l (hypoglycemia) and to 102 +/- 10 pmol/l (euglycemia). Arterial
      blood glucose decreased from 4.5 +/-0.2 to 3.0 +/- 0.1 mmol/l during hypoglycemia
      but did not change during euglycemia (4.3 +/- 0.2 mmol/l). After 150 min,
      endogenous glucose production reached a plateau value that was higher during
      hypoglycemia (10.3 +/0.6 micromol x kg(-1) x min(-1)) than during euglycemia
      (5.73 +/-0.6 micromol x kg(-1) x min(-1), P < 0.001). Hypoglycemia was associated
      with a rise in renal glucose production (RGP) from 3.0 +/- 0.7 to 5.4 +/- 0.6
      micromol x kg(-1) x min(-1) (P < 0.05), although glucose utilization remained the
      same (2.0 +/- 0.8 vs. 2.1 +/-0.6 micromol x kg(-1) x min(-1)). As a result, net
      renal glucose output increased from 1.0 +/- 0.3 to 3.3 +/- 0.40 micromol x kg(-1)
      x min(-1). Elevations in net renal uptake of lactate (2.4 +/- 0.5 to 3.5 +/- 0.7
      vs. 2.8 +/- 0.4 micromol x kg(-1) x min(-1)), glycerol (0.6 +/- 0.3 to 1.3 +/-
      0.5 vs. 0.4 +/- 0.2 micromol x kg(-1) x min(-1)), and glutamine (0.7 +/- 0.2 to
      1.1 +/- 0.3 vs. 0.1 +/- 0.3 micromol x kg(-1) x min(-1)) during hypoglycemia
      versus euglycemia (P < 0.05) could account for nearly 60% of all glucose carbons
      released in the renal vein during hypoglycemia. Our data indicate that extraction
      of circulating gluconeogenic precursors by the kidney is enhanced and responsible
      for a substantial fraction of the compensatory rise in RGP during sustained
      hypoglycemia. Increased renal gluconeogenesis from circulating substrates
      represents an additional physiological mechanism by which the decrease in blood
      glucose concentration is attenuated in humans.

PMID- 10909978
TI  - The IR1152 mutant insulin receptor selectively impairs insulin action in skeletal
      muscle but not in liver.
AB  - In patients harboring the IR1152 mutant insulin receptor, hepatic glucose
      production was normally suppressed by insulin. Hepatocytes without the insulin
      receptor gene and expressing IR1152 (Hep(MUT)) also showed normal insulin
      suppression of glucose production and full insulin response of glycogen synthase.
      In contrast, expression of the IR1152 mutant in skeletal muscle maximally
      increased glucose uptake and storage, preventing further insulin stimulation. IRS
      1 phosphorylation was normally stimulated by insulin in both intact Hep(MUT) and
      L6 skeletal muscle cells expressing the IR1152 mutant (L6(MUT)). At variance, IRS
      2 phosphorylation exhibited high basal levels with no further insulin-dependent
      increase in L6(MUT) but almost normal phosphorylation, both basal and insulin
      stimulated, in the Hep(MUT) cells. In vitro, IR1152 mutant preparations from both
      the L6(MUT) and the Hep(MUT) cells exhibited increased basal and no insulin
      stimulated phosphorylation of IRS-2 immobilized from either muscle or liver
      cells. IR1152 internalization in liver and muscle cells closely paralleled the
      ability of this mutant to phosphorylate IRS-2 in vivo in these cells. Block of
      receptor internalization (wild-type and mutant) in the liver and muscle cells
      also inhibited IRS-2, but not IRS-1, phosphorylation. Thus, the mechanisms
      controlling insulin receptor internalization differ in liver and skeletal muscle
      cells and may enable IR1152 to control glucose metabolism selectively in liver.
      In both cell types, receptor internalization seems necessary for IRS-2 but not
      IRS-1 phosphorylation.

PMID- 10909979
TI  - Transient effects of long-term leptin supplementation in the prevention of diet
      induced obesity in mice.
AB  - Low plasma leptin levels have been shown to be associated with the development of
      obesity in mice as well as in humans. The present study was undertaken to
      determine if raising plasma leptin levels of obesity-prone C57BL/6J (B6) mice to
      those seen in obesity-resistant A/J mice would prevent the development of diet
      induced obesity. Four-week-old B6 (n = 40) and A/J (n = 10) male mice were weaned
      onto a low-fat (11% kcal) diet. When the animals weighed 20 g, their diets were
      changed to a high-fat (HF) diet (58% kcal), and a continuous infusion of leptin
      (0.4 mg x kg(-1) x day(-1)) or phosphate-buffered saline (control) was started
      using Alzet minipumps. The A/J mice were not treated but were included to monitor
      the efficacy of the minipumps in raising plasma leptin in B6 mice. The mice were
      followed for 12 weeks. Chronic treatment with leptin for 4 weeks raised plasma
      levels in B6 mice to that of A/J mice. Plasma leptin in B6 control mice remained
      significantly lower than A/J mice through week 4. By week 8, leptin levels in the
      B6 control group had risen and were similar to A/J mice. Although there were
      significant weight differences between B6 treated and B6 control groups for 2-3
      weeks after pump implantation, these differences were transient. Ultimately,
      there were no weight differences between the B6 treated and B6 control groups.
      There were no differences in plasma glucose between B6 treated and control
      groups. Plasma insulin values were also not different between the 2 groups. There
      was no effect of leptin supplementation on locomotor activity or food intake in
      B6 mice. In summary, this study demonstrates that leptin supplementation in
      animals that show low plasma leptin levels in response to fat feeding may slow
      but does not prevent the subsequent development of diet-induced obesity.

PMID- 10909980
TI  - Glucose-mediated glucose disposal in insulin-resistant normoglycemic relatives of
      type 2 diabetic patients.
AB  - With the aim of investigating glucose-mediated glucose disposal (glucose
      effectiveness [GE]) in 15 (3 female and 12 male subjects) insulin-resistant
      normoglycemic relatives of patients with type 2 diabetes (DM2), and 15 age-, sex
      , and BMI-matched control subjects without a family history of DM2, we performed
      2 studies: 1) a 5-h euglycemic near-normoinsulinemic pancreatic clamp with
      somatostatin (360 microg/h), insulin (0.25 mU x kg(-1) x min(-1)), glucagon (0.5
      ng x kg(-1) x min(-1)), growth hormone (6 ng x kg(-1) x min(-1)), and tritiated
      glucose infusion and indirect calorimetry; and 2) on a separate day, an identical
      5-h clamp but at hyperglycemia (approximately 12 mmol/l) over the last 2 h.
      Fasting plasma insulin (PI) concentrations were elevated in the relatives
      compared with control subjects (49 +/- 6 vs. 32 +/- 5 pmol/l, P < 0.04), whereas
      plasma glucose (PG) was not (5.6 +/- 0.1 vs. 5.5 +/-0.1 mmol/l). At the end
      (i.e., 4.5-5.0 h) of the euglycemic clamp (PG, 6.1 +/- 0.4 vs. 5.6 +/- 0.1
      mmol/l; PI, 78 +/- 5 vs. 73 +/-6 pmol/l), peripheral glucose uptake
      (Rd(euglycemia)) was decreased in the relatives (2.93 +/- 0.08 vs. 3.70 +/-0.23
      mg x min(-1) x kg(-1) fat free mass [FFM], P < 0.005), due to a decreased
      nonoxidative glucose disposal (0.83 +/-0.21 vs. 1.62 +/- 0.19 mg x min(-1) x kg(
      1) FFM, P < 0.01), but hepatic glucose production (HGP) was increased (1.97 +/
      0.19 vs. 1.50 +/- 0.13 mg x min(-1) x kg(-1) FFM, P < 0.05). At the matched end
      of the hyperglycemic clamp (PG, 12.7 +/-0.2 vs. 12.6 +/- 0.2 mmol/l; PI, 87 +/- 5
      vs. 78 +/- 7 pmol/l), peripheral glucose disposal (Rd(hyperglycemia)) (5.52 +/-
      0.22 vs. 5.92 +/- 0.29 mg x min(-1) x kg(-1) FFM, NS), nonoxidative glucose
      disposal (2.93 +/- 0.18 vs. 2.78 +/- 0.25 mg x min(-1) x kg(-1) FFM, NS), and
      HGP(hyperglycemia) (1.20 +/- 0.09 vs. 1.37 +/-0.23 mg x min(-1) x kg(-1) FFM, NS)
      were all identical. When the effectiveness of glucose itself on glucose uptake
      and production [(Rd(hyperglycemia) - Rd(euglycemia))/deltaPG and (HGP(euglycemia)
      HGP(hyperglycemia))/deltaPG] was calculated, the relatives had a 22% increase in
      peripheral uptake (0.022 +/- 0.002 vs. 0.018 +/- 0.002 mg x min(-1) x kg(-1) FFM
      per mg/dl), due to a significantly increased nonoxidative glucose metabolism and
      enhanced suppression of HGP (0.0076 +/- 0.0021 vs. 0.0011 +/- 0.0022 mg x min(-1)
      x kg(-1) FFM per mg/dl, P < 0.05). In conclusion, in insulin-resistant relatives
      of DM2 patients, whole-body glucose-mediated glucose disposal is increased by GE
      enhancement of the muscle nonoxidative glucose pathway and by GE enhancement of
      the suppression of HGP. These mechanisms may represent a compensatory mechanism
      to the ongoing insulin resistance of these relatives.

PMID- 10909981
TI  - Obesity is associated with a decreased leptin transport across the blood-brain
      barrier in rats.
AB  - Leptin exerts important effects on the regulation of food intake and energy
      expenditure by acting in the brain. Leptin is secreted by adipocytes into the
      bloodstream and must gain access to specific regions in the brain involved in
      regulating energy balance. Its action is mediated by interaction with a receptor
      that is mainly expressed in the hypothalamus but is also present in other
      cerebral areas. To reach these target areas, leptin most likely needs to cross
      the blood-brain barrier (BBB). In this study, we compared the permeability of
      leptin at the BBB in homozygous lean (FA/FA), high-fat diet-induced (HFD) obese
      rats (FA/FA rats on a highfat diet), and genetically obese fa/fa Zucker rats by
      quantifying the permeability coefficient surface area (PS) product after
      correction for the residual plasma volume (Vp) occupied by leptin in the vessel
      bed of different brain regions. The intravenous bolus injection technique was
      used in the cannulated brachial vein and artery using leptin radioiodinated with
      2 isotopes of iodine (125I and 131I) to separately determine the PS and Vp
      values. The PS for leptin at the BBB in lean FA/FA rats ranged from 11.0 +/- 1.6
      at the cortex to 14.8 +/- 1.4 x 10(-6) ml x g(-1) x ml(-1) at the posterior
      hypothalamus. The PS for leptin in HFD obese FA/FA and obese fa/fa rats ranged
      from 3.0- to 4.0-fold lower than in lean FA/FA rats. The Vp values were not
      significantly different among the 3 groups studied. SDS-PAGE analysis of the
      radioiodinated leptin after 60 min of uptake revealed intact protein in the 8
      different brain regions. Plasma leptin levels were significantly higher in both
      obese rat groups compared with those in lean FA/FA rats. Leptin levels in
      cerebrospinal fluid were not significantly different among the 3 groups of rats.
      These findings strongly suggest that the leptin receptor (OB-R) in the BBB can be
      easily saturated. Saturation of the BBB OB-R in obese individuals would explain
      the defect in leptin transport into the brain described in this study.

PMID- 10909982
TI  - Impaired expression of the uncoupling protein-3 gene in skeletal muscle during
      lactation: fibrates and troglitazone reverse lactation-induced downregulation of
      the uncoupling protein-3 gene.
AB  - The expression of uncoupling protein (UCP)-3 mRNA in skeletal muscle is
      dramatically reduced during lactation in mice. The reduction in UCP-3 mRNA levels
      lowers the amount of the UCP-3 protein in skeletal muscle mitochondria during
      lactation. Spontaneous or abrupt weaning reverses the downregulation of the UCP-3
      mRNA but not the reduction in UCP-3 protein levels. In lactating and virgin mice,
      however, fasting increases UCP-3 mRNA levels. Changes in UCP-3 mRNA occur in
      parallel with modifications in the levels of free fatty acids, which are reduced
      in lactation and are upregulated due to weaning or fasting. Modifications in the
      energy nutritional stress of lactating dams achieved by manipulating litter sizes
      do not influence UCP-3 mRNA levels in skeletal muscle. Conversely, when mice are
      fed a high-fat diet after parturition, the downregulation of UCP-3 mRNA and UCP-3
      protein levels due to lactation is partially reversed, as is the reduction in
      serum free fatty acid levels. Treatment of lactating mice with a single injection
      of bezafibrate, an activator of the peroxisome proliferator-activated receptor
      (PPAR), raises UCP-3 mRNA in skeletal muscle to levels similar to those in virgin
      mice. 4-chloro-6-[(2,3-xylidine)-pirimidinylthio] acetic acid (WY-14,643), a
      specific ligand of the PPAR-alpha subtype, causes the most dramatic increase in
      UCP-3 mRNA, whereas troglitazone, a specific activator of PPAR-gamma, also
      significantly increases UCP-3 mRNA abundance in skeletal muscle of lactating
      mice. However, in virgin mice, bezafibrate and WY-14,643 do not significantly
      affect UCP-3 mRNA expression, whereas troglitazone is at least as effective as it
      is in lactating dams. It is proposed that the UCP-3 gene is regulated in skeletal
      muscle during lactation in response to changes in circulating free fatty acids by
      mechanisms involving activation of PPARs. The impaired expression of the UCP-3
      gene is consistent with the involvement of UCP-3 gene regulation in the reduction
      of the use of fatty acids as fuel by the skeletal muscle and in impaired
      adaptative thermogenesis, both of which are major metabolic adaptations that
      occur during lactation.

PMID- 10909983
TI  - Free fatty acid elevation impairs insulin-mediated vasodilation and nitric oxide
      production.
AB  - The effect and time course of free fatty acid (FFA) elevation on insulin-mediated
      vasodilation (IMV) and the relationship of FFA elevation to changes in insulin
      mediated glucose uptake was studied. Two groups of lean insulin-sensitive
      subjects underwent euglycemic-hyperinsulinemic (40 mU x m(-2) x min(-1)) clamp
      studies with and without superimposed FFA elevation on 2 occasions approximately
      4 weeks apart. Groups differed only by duration of FFA elevation, either short (2
      4 h, n = 12) or long (8 h, n = 7). On both occasions, rates of whole-body glucose
      uptake were measured, and changes in leg blood flow (LBF) and femoral vein nitric
      oxide nitrite plus nitrate (NOx) flux in response to the clamps were determined.
      Short FFA infusion did not have any significant effect on the parameters of
      interest. In contrast, long FFA infusion decreased rates of whole-body glucose
      uptake from 47.7 +/-2.8 to 32.2 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.01),
      insulin-mediated increases in LBF from 66 +/- 8 to 37 +/- 7% (P < 0.05), and
      insulin-induced increases in NOx flux from 25 +/- 9 to 5 +/- 9% (P < 0.05).
      Importantly, throughout all groups, FFA-induced changes in whole-body glucose
      uptake correlated significantly with FFA-induced changes in insulin-mediated
      increases in LBF (r = 0.706, P < 0.001), which indicates coupling of metabolic
      and vascular effects. In a different protocol, short FFA elevation blunted the
      LBF response to NG-monomethyl-L-arginine (L-NMMA), which is an inhibitor of NO
      synthase. LBF in response to L-NMMA decreased by 17.3 +/- 2.4 and 9.0 +/- 1.4% in
      the groups without and with FFA elevation, respectively (P < 0.05), which
      indicates that FFA elevation interferes with shear stress-induced NO production.
      Thus, impairment of shear stress-induced vasodilation and IMV by FFA elevation
      occurs with different time courses, and impairment of IMV occurs only if glucose
      metabolism is concomitantly reduced. These findings suggest that NO production in
      response to the different stimuli may be mediated via different signaling
      pathways. FFA-induced reduction in NO production may contribute to the higher
      incidence of hypertension and macrovascular disease in insulin-resistant
      patients.

PMID- 10909984
TI  - Induction of endothelin-1 expression by glucose: an effect of protein kinase C
      activation.
AB  - Enhanced actions or levels of endothelin-1 (ET-1), a potent vasoconstrictor, have
      been associated with decreased blood flow in the retina and peripheral nerves of
      diabetic animals and may be related to the development of pathologies in these
      tissues. Hyperglycemia has been postulated to increase ET-1 secretion in
      endothelial cells. We have characterized the mechanism by which elevation of
      glucose is increasing ET-1 mRNA expression in capillary bovine retinal
      endothelial cells (BREC) and bovine retinal pericytes (BRPC). Elevation of
      glucose, but not mannitol, from 5.5 to 25 mmol/l for 3 days increased membranous
      protein kinase C (PKC) activities and ET-1 mRNA in parallel levels by 2-fold in
      BREC and BRPC. These effects were reversed by decreasing glucose levels to 5.5
      mmol/l for an additional 2 days. Glucose-induced ET-1 overexpression was
      inhibited by a general PKC inhibitor, GF109203X, and a mitogen-activated protein
      kinase kinase inhibitor, PD98059, but not by wortmannin, a phosphatidylinositol 3
      kinase inhibitor. By immunoblot analysis, PKC-beta2 and -delta isoforms in BREC
      were significantly increased relative to other isoforms in the membranous
      fractions when glucose level was increased. Overexpression of PKC-beta1 and 
      delta isoforms but not PKC-zeta isoform by adenovirus vectors containing the
      respective cDNA enhanced in parallel PKC activities, proteins, and basal and
      glucose-induced ET-1 mRNA expression by at least 2-fold. These results showed
      that enhanced ET-1 expression induced by hyperglycemia in diabetes is partly due
      to activation of PKC-beta and -delta isoforms, suggesting that inhibition of
      these PKC isoforms may prevent early changes in diabetic retinopathy and
      neuropathy.

PMID- 10909985
TI  - The diabetic milieu modulates the advanced glycation end product-receptor complex
      in the mesangium by inducing or upregulating galectin-3 expression.
AB  - Nonenzymatic glycation has been implicated in the pathogenesis of the
      dysregulated tissue remodeling that characterizes diabetic glomerulopathy, via
      the formation of advanced glycation end products (AGEs) and their binding to cell
      surface receptors. Several AGE-binding proteins have been identified so far,
      including p60, p90, and the adhesive and growth-regulating lectin galectin-3 (Gal
      3), the components of the so-called AGE-receptor complex. This study aimed to
      evaluate the mesangial expression of the AGE-receptor complex and its modulation
      by the diabetic milieu, both in vivo, in non-diabetic versus streptozotocin
      induced diabetic rats, and in vitro, in mesangial cells exposed to either normal
      glucose (NG) levels (5.5 mmol/l), as compared with high glucose (HG) levels (30
      mmol/l) and iso-osmolar mannitol (M), or to native bovine serum albumin (BSA), as
      compared with glycated BSA with AGE formation (BSA-AGE) and glycated BSA in which
      AGE formation was prevented by aminoguanidine (BSA-AM). In vivo, Gal-3 protein
      and mRNA were not detectable in glomeruli from nondiabetic rats until 12 months
      after initiating the study. On the contrary, in diabetic rats, Gal-3 expression
      was observed at 2 months of disease duration, and it increased thereafter. Both
      p60 and p90 immunoreactivities were observed at the glomerular level with
      slightly increased expression of p90, but not p60, in diabetic versus nondiabetic
      animals. In vitro, Gal-3 was not detectable in mesangial cells cultured in NG
      (although it became evident after a certain number of passages in culture),
      whereas Gal-3 was detectable in cells grown on BSA. Prolonged exposure (2-4
      weeks) of mesangial cells to HG but not to M, as well as growing cells on BSA-AGE
      and, to a lesser extent, BSA-AM, induced or significantly increased the
      expression of Gal-3, both protein (up to 2.65-fold) and mRNA (up to 3.10-fold)
      and its secretion in the medium (by approximately 50%). Both p60 and p90 were
      demonstrated in mesangial cells under NG conditions, and the expression of p90,
      but not p60, was upregulated by approximately 20% by HG or BSA-AGE. These results
      indicate that 1) under basal conditions, Gal-3, unlike p90 and p60, is not
      detectable in the mesangium but becomes expressed with aging and 2) the diabetic
      milieu induces or upregulates Gal-3 production, whereas it increases only
      slightly the expression of p90, but not p60. Gal-3 expression or overexpression
      may modulate the AGE-receptor-mediated events by modifying the function of the
      AGE-receptor complex. Additionally, it may exert direct effects on tissue
      remodeling by virtue of its adhesive and growth-regulating properties.

PMID- 10909986
TI  - Increased circulating nitric oxide in young patients with type 1 diabetes and
      persistent microalbuminuria: relation to glomerular hyperfiltration.
AB  - Hyperglycemia has been causally linked to vascular and glomerular dysfunction by
      a variety of biochemical mechanisms, including a glucose-dependent abnormality in
      nitric oxide (NO) production and action. NO is a candidate for mediating
      hyperfiltration and the increased vascular permeability induced by diabetes.
      Serum nitrite and nitrate (NO2-+ NO3-) concentrations were assessed as an index
      of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with
      and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200
      microg/min), compared with a well-balanced group of healthy control subjects. In
      all subjects, glomerular filtration rate (GFR) was determined by radionuclide
      imaging. Our study showed that NO2- + NO3- serum content and GFR values were
      significantly higher in microalbuminuric diabetic patients than in the other 2
      groups. GFR was significantly and positively related to AER levels (r2 = 0.75, P
      < 0.0001), whereas NO2- + NO3- serum content was independently associated with
      both AER and GFR values (beta = 2.086, P = 0.05, beta = 1.273, P = 0.0085,
      respectively), suggesting a strong link between circulating NO, glomerular
      hyperfiltration, and microalbuminuria in young type 1 diabetic patients with
      early nephropathy. Interestingly, mean HbA1c, serum concentration was
      significantly higher in microalbuminuric than in normoalbuminuric diabetic
      subjects (P < 0.05) and was independently associated with AER values, suggesting
      a role for chronic hyperglycemia in the genesis of diabetic nephropathy.
      Moreover, HbA1c serum concentration was significantly and positively related to
      NO2 + NO3 serum content (r2 = 0.45, P = 0.0063) and GFR values (r2 = 0.57, P =
      0.0011), suggesting that chronic hyperglycemia may act through a mechanism that
      involves increased NO generation and/or action. In conclusion, we suggest that in
      young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is
      associated with an increased NO biosynthesis and action that contributes to
      generating glomerular hyperfiltration and persistent microalbuminuria.

PMID- 10909987
TI  - Naturally occurring amino acid substitutions at Arg1174 in the human insulin
      receptor result in differential effects on receptor biosynthesis and hybrid
      formation, leading to discordant clinical phenotypes.
AB  - Missense mutations in the tyrosine kinase domain of the human insulin receptor
      frequently result in a dominantly inherited form of insulin resistance. We noted
      a marked disparity in the clinical phenotypes of our study subjects with
      different missense mutations at the same residue (Arg1174) of the insulin
      receptor. Subjects with a tryptophan substitution (W) were only moderately
      hyperinsulinemic, whereas those with a glutamine substitution (Q) had severe
      clinical and biochemical insulin resistance. Studies were undertaken to explore
      the molecular mechanisms underlying these differences. Both W and Q mutant
      receptors bound insulin normally but were kinase inactive. The W mutation
      resulted in more rapid degradation of newly synthesized mutant receptor, which
      contrasted with the near-normal biosynthesis of the Q receptor. The propensity of
      the W receptor to form hybrids with the cotransfected wild-type (WT) receptor was
      also markedly impaired compared with the Q receptor, to an extent greater than
      could be explained by lower steady-state expression. Thus, the more clinically
      benign consequences of the heterozygous W mutant receptor are likely to relate to
      its impaired biosynthesis and/or reduced capacity to form hybrids with WT
      receptors. In addition to providing an explanation for the milder phenotype of
      1174W versus 1174Q carriers, these studies provide further support for the notion
      that the dominant-negative effect of insulin receptor tyrosine kinase mutations
      involves the competition between inactive mutant homodimers and WT/mutant hybrids
      with active WT homodimers for both ligands and intracellular substrates.

PMID- 10909988
TI  - A new mitochondrial DNA mutation at 14577 T/C is probably a major pathogenic
      mutation for maternally inherited type 2 diabetes.
AB  - From a family of 16 diabetic patients with typical maternal inheritance, we
      investigated a 69-year-old woman with type 2 diabetes. The proband showed no
      major deletions in the mitochondrial DNA (mtDNA). Direct sequencing revealed 7
      missense and 5 ribosomal RNA homoplasmic nucleotide substitutions when compared
      with the Cambridge Sequence and its recent revision. When compared with the
      control cybrid cells, the proband cybrid cells showed 6 nucleotide substitutions.
      Among these, 14577 T/C, which turned out to be 98.9% heteroplasmic, is a new
      missense substitution in the NADH dehydrogenase 6 gene. We also observed 2 other
      patients with 14577 T/C substitution from another group of 252 unrelated diabetic
      patients, whereas no individual from a group of 529 control subjects had 14577
      T/C substitution. Furthermore, these 6 substitutions were in linkage
      disequilibrium. Mitochondrial respiratory chain complex I activity and O2
      consumption rates of the proband cybrid cells, which were obtained by the fusion
      of mtDNA-deleted (rho0) HeLa cells and mtDNA from the proband, showed 64.5 and
      61.5% reductions, respectively, compared with control cybrid cells. The present
      study strongly indicates that the new mtDNA mutation at 14577 T/C is probably a
      major pathogenic mutation for type 2 diabetes in this family.

PMID- 10909989
TI  - Serum leptin concentrations during severe protein-energy malnutrition:
      correlation with growth parameters and endocrine function.
AB  - Circulating leptin, insulin, insulin-like growth factor-I (IGF-I), cortisol, and
      albumin concentrations and the growth hormone (GH) response to provocation were
      measured in 30 children with severe protein-energy malnutrition (PEM), 20 with
      marasmus and 10 with kwashiorkor, as well as 10 age-matched normal children (body
      mass index [BMI] >50th and <90th percentile for age and sex) and 10 prepubertal
      obese children (BMI >95th percentile for age and sex). Patients with PEM had a
      significantly lower BMI, midarm circumference (MAC), and skinfold thickness (SFT)
      compared with the age-matched control group. Basal cortisol and GH concentrations
      were significantly higher in the malnourished groups versus controls. Leptin and
      IGF-I were significantly lower in the marasmic and kwashiorkor groups versus
      normal children. Fasting insulin levels were significantly decreased in the
      kwashiorkor group compared with marasmic and normal children. The BMI correlated
      significantly with leptin (r = .77, P < .001), basal insulin (r = .61, P < .001),
      and IGF-I (r = .77, P < .001) and negatively with basal GH (r = -.52, P < .001).
      These findings suggest that during prolonged nutritional deprivation, the
      decreased energy intake, diminished subcutaneous fat mass, and declining insulin
      (and possibly IGF-I) concentration suppress leptin production. In support of this
      view, serum leptin levels were positively correlated with triceps, scapular, and
      abdominal SFT (r = .763, .75, and .744, respectively, P < .0001) in all of the
      children. Moreover, basal insulin and circulating IGF-I were correlated
      significantly with leptin concentrations (r = .47 and .62, respectively, P <
      .001). Basal levels of cortisol and GH were significantly elevated in the 2
      groups with severe PEM. It is suggested that low leptin levels can stimulate the
      hypothalamic-pituitary-adrenal (HPA) axis and possibly the hypothalamic-pituitary
      GH axis to maintain the high cortisol and GH levels necessary for effective
      lipolysis to ensure a fuel (fatty acids) supply for the metabolism of brain and
      peripheral tissue during nutritional deprivation. In summary, during prolonged
      PEM, the decreased synthesis of IGF-I and the low level of insulin and/or its
      diminished effect due to an insulin-resistant status in the presence of high
      circulating GH and cortisol levels ensure substrate diversion away from growth
      toward metabolic homeostasis. Leptin appears to be an important signal in the
      process of metabolic/endocrine adaptation to prolonged nutritional deprivation.

PMID- 10909990
TI  - Effects of exercise on plasma high-density lipoprotein cholesteryl ester
      metabolism in male and female miniature swine.
AB  - We studied the effects of exercise on high-density lipoprotein (HDL) cholesteryl
      ester (CE) metabolism in 6 male and 6 female miniature pigs fed a commercial
      swine diet supplemented with cholesterol and fat. The diets were fed for a total
      period of 20 weeks. During the last 12 weeks of the feeding period, the pigs were
      exercised on a motorized treadmill 5 days per week for 45 min/d at a speed of 9.5
      to 10.0 km/h at 0% grade. Homologous HDL preparations were radiolabeled with
      cholesteryl (1-14C)oleate and intravenously administered to the pigs, followed by
      blood sampling at the appropriate time points and measurement of radiolabeled HDL
      CE. This was performed while the animals were sedentary and after the exercise
      period. Plasma cholesterol increased after the exercise protocol from 7.21 +/-
      1.90 to 8.50 +/- 2.81 mmol/L (mean +/- SD, n = 6) in the females and from 8.11 +/
      3.61 to 10.07 +/- 3.61 in the males. HDL CE transport rates in female pigs were
      significantly lower (23%) after the exercise protocol (118 +/- 14 v 91 +/- 14
      micromol/h/L plasma). HDL CE transport rates in the males were also lower (11%)
      after exercise (90 +/- 20 v 80 +/- 18 micromol/h/L plasma), but this effect was
      not statistically significant. Further, the residence time or life span of HDL CE
      was significantly longer after the exercise protocol in both male and female
      pigs. Thus, the results of this study suggest that exercise reduces the transport
      rate of HDL CE and prolongs the life span of HDL CE in hypercholesterolemic pigs.

PMID- 10909991
TI  - Lower beta-cell secretion in physically active first-degree relatives of type 2
      diabetes patients.
AB  - Regular physical activity may prevent or postpone type 2 diabetes, and is thought
      to be related to an increase of insulin sensitivity. We studied whether
      physically active, glucose-tolerant first-degree relatives of type 2 diabetes
      patients differ in glucose tolerance (oral glucose tolerance test [OGTT]) and
      insulin secretion (hyperglycemic glucose clamp) from less active first-degree
      relatives. A group of 37 relatives was split into 2 subgroups according to the
      sex-specific median of the sports index, assessed by a questionnaire, as the
      cutoff point. Blood glucose levels during the OGTT were lower in the highly
      active subgroup versus the less active counterparts (multivariate ANOVA [MANOVA],
      P = .011), but the plasma insulin levels were similar. First-phase secretion was
      not different in the highly active group versus the less active group, but second
      phase secretion (average plasma insulin in the third hour) was significantly
      lower (P = .016). As expected, the insulin sensitivity index (ISI) was higher in
      the highly active subgroup (P= .011). Subdivision into subgroups with high or low
      maximal O2 consumption (VO2max) resulted in similar differences, but these were
      not significant. In a group of 21 controls, the results resembled the values in
      the relatives but were less often statistically significant. In conclusion,
      regular physical activity not only is associated with increased insulin
      sensitivity but also downregulates the pancreatic beta cell. This downregulation
      may provide an extra mechanism by which physical activity diminishes the
      development of type 2 diabetes.

PMID- 10909992
TI  - Indomethacin decreases insulin secretion in patients with type 2 diabetes
      mellitus.
AB  - In healthy subjects, basal endogenous glucose production (EGP) is partly
      regulated by paracrine intrahepatic factors. Administration of indomethacin, an
      inhibitor of prostaglandin synthesis, resulted in a transient stimulation of EGP
      without changes in glucoregulatory hormone concentrations. It is unknown whether
      similar paracrine factors influence basal EGP in type 2 diabetes mellitus. The
      effects of 150 mg indomethacin, a nonendocrine stimulator of glucose production
      in healthy adults, and placebo on EGP were measured in a randomized placebo
      controlled study in patients with type 2 diabetes mellitus (3 men and 3 women;
      mean age, 58.5 years; mean body mass index, 28.6 kg x m(-2)). EGP was measured
      before and for 6 hours after administration of placebo/indomethacin, by a primed,
      continuous infusion of [6,6-2H2]glucose. After indomethacin, plasma glucose and
      EGP increased in all subjects by 14% (P < .05) and 48% (P < .05), respectively.
      In the control experiment, plasma glucose and EGP declined gradually in all
      subjects by 22% (P < .001) and 17% (P = .004), respectively. The stimulation of
      glucose production coincided with the inhibition of insulin secretion by 52%
      within 1 hour after administration of indomethacin (P < .001). In the control
      experiment, insulin secretion decreased gradually by 18% after 6 hours (P <
      .001). Thus, indomethacin inhibits insulin secretion and stimulates EGP in type 2
      diabetes.

PMID- 10909993
TI  - The 4G/4G polymorphism of the hypofibrinolytic plasminogen activator inhibitor
      type 1 gene: an independent risk factor for serious pregnancy complications.
AB  - The specific aim of the current study of 133 women with at least 1 pregnancy and
      measures of hypofibrinolytic and thrombophilic gene mutations was to determine
      retrospectively whether the mutations were associated with adverse pregnancy
      outcomes including prematurity, miscarriage, stillbirth, intrauterine growth
      retardation (IUGR), eclampsia, and abruptio placentae. Four gene mutations
      (factor V Leiden, methylenetetrahydrofolate reductase [MTHFR], prothrombin, and
      4G/5G polymorphism of the plasminogen activator inhibitor type 1 [PAI-1] gene)
      were assessed by polymerase chain reaction (PCR). One hundred twenty-two women
      were genotyped for all 4 genes and divided into gene mutation (n = 68) and non
      gene (n = 54) groups. The gene mutation group included those with at least 1
      thrombophilic mutation (heterozygous for factor V Leiden, heterozygous for
      prothrombin, and homozygous for MTHFR), or hypofibrinolysis with homozygosity for
      the 4G polymorphism of the PAI-1 gene. The non-gene mutation group included those
      with no mutation for all 4 genes (wild-type normal) or who were wild-type normal
      for the prothrombin and factor V Leiden mutations and heterozygous for MTHFR
      and/or 4G/5G for the PAI-1 gene, neither heterozygosity associated with
      coagulation abnormalities. The 68 women with gene mutations, versus 54 in the non
      gene mutation group, has more prematurity (10% v 4%, chi2 = 5.4, P = .021), more
      IUGR (3% v 0%, P = .035), and more total complications of pregnancy (37% v 21%,
      chi2 = 11.6, P = .001). The number of pregnancies (P = .0001) and 4G/4G
      polymorphism of the PAI-1 gene (P = .029) were positively associated with
      complications of pregnancy by stepwise logistic regression when the age, number
      of pregnancies, and all 4 gene mutations were the explanatory variables.
      Heritable hypofibrinolysis, mediated by 4G/4G homozygosity for the PAI-1 gene, is
      an independent significant, potentially reversible risk factor for pregnancy
      complications, probably acting through thrombotic induction of placental
      insufficiency.

PMID- 10909994
TI  - Streptozotocin-induced diabetic pregnant rats exhibit signs and symptoms
      mimicking preeclampsia.
AB  - The number of patients with hypertension, obesity, diabetes, and hyperlipidemia
      is increasing. This tendency is observed in pregnant women, in whom many
      obstetrical and perinatal complications occur. The prevention of these
      abnormalities is important in reducing perinatal mortality and the risk of
      coronary disease. We established a pregnant rat model with diabetes and signs and
      symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or
      citrate buffer was injected into the tail vein. After STZ administration, plasma
      glucose was increased within 48 hours and sustained at a high level until day 20
      of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers
      were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ
      treated versus control rats. The systolic blood pressure, urinary protein, and
      hematocrit were increased significantly in STZ-treated rats. Total cholesterol
      and triglycerides were also elevated in STZ-treated rats, but plasma leptin
      levels were decreased. The STZ-induced diabetic pregnant rat model exhibited
      preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine
      growth restriction. This model closely mimics the features of human pregnancy
      complicated by diabetes and is useful for the basic study of the pathophysiology
      of pregnancy with diabetes.

PMID- 10909995
TI  - Effect of short-term exercise training on leptin and insulin action.
AB  - The purpose of the study was to determine the effect of short-term exercise
      training (7 consecutive days for 60 min/d at 75% maximal oxygen consumption [VO2
      max]), which did not change body mass on fasting plasma leptin concentration and
      insulin action. Young, lean subjects (n = 16; age, 21.9 +/- 0.6 years; body fat,
      17.5% +/- 1.5%) and older subjects with relatively more adipose tissue (n = 14;
      age, 58.6 +/- 1.4 years; body fat, 28.3% +/- 1.3%) were studied (mean +/- SE).
      Fasting plasma leptin was significantly (P < .05) related to adiposity (fat mass,
      r = .58; % body fat, r = .76) in this population. Body mass did not change (P <
      .05) in any of the groups with training (71.8 +/- 2.5 v 71.9 +/- 2.5 kg). The
      insulin sensitivity index (SI determined from an intravenous glucose tolerance
      test (IVGTT) improved significantly (P < .05) in both the young group (4.8 +/-
      0.6 v6.9 +/- 0.8 x 10(-4)/ min (microU/mL) and the older group (3.2 +/- 0.6 v 5.9
      +/- 1.0 x 10(-4)/min (microU/mL)). Fasting leptin did not change with training in
      either group (10.4 +/- 1.6 v 9.2 +/- 1.0 ng/mL). These findings suggest that
      exercise does not independently affect the fasting plasma leptin concentration
      and the improvement in insulin action with exercise is not associated with an
      alteration in fasting leptin in healthy sedentary lean and relatively lean
      subjects.

PMID- 10909996
TI  - Effect of JTT-501 on net hepatic glucose balance and peripheral glucose uptake in
      alloxan-induced diabetic dogs.
AB  - JTT-501, a new insulin sensitizer, improves peripheral glucose uptake in insulin
      resistant animals such as KK-Ay mice and Zucker fatty rats. However, the effect
      of JTT-501 on hepatic glucose metabolism has not been addressed. To investigate
      this effect, experiments were performed on 6 alloxan-diabetic dogs. Three
      experiments were conducted for each dog: the treatment experiment, which followed
      a 10-day oral treatment with JTT-501 30 mg x kg(-1) x d(-1), and 2 control
      experiments 2 weeks before and 2 weeks after the treatment experiment. A
      hyperinsulinemic-hyperglycemic clamp was performed with the tracer dilution
      method (intraportal insulin infusion rate, 18 pmol x kg(-1) x min(-1)). Arterial
      hyperglycemia (approximately 10 mmol/L) was maintained by adjusting the
      peripheral glucose infusion rate. After a 45-minute basal period (period I),
      portal glucose infusion (22.2 micromol x kg(-1)min(-1)) was administered for 120
      minutes (period II). This was followed by a 90-minutes recovery period (period
      III). JTT-501 increased insulin-stimulated glucose utilization (P < .05) and
      enhanced insulin-mediated suppression of glucose production (P < .05) in periods
      I and III. Net hepatic glucose balance (NHGB) determined by the arterial-venous
      (A-V) difference method was increased by JTT-501 in period II (P < .01). We
      conclude that JTT-501 enhances both hepatic and peripheral insulin sensitivity
      and therefore may have important therapeutic effects in type 2 diabetes.

PMID- 10909997
TI  - The effects ex vivo and in vitro of insulin and C-peptide on Na/K adenosine
      triphosphatase activity in red blood cell membranes of type 1 diabetic patients.
AB  - The decrease in Na/K adenosine triphosphatase (ATPase) activity observed in
      several tissues of type 1 diabetic patients is thought to play a role in the
      development of long-term complications. Infusion of insulin may restore this
      enzyme activity in red blood cells (RBCs), and recent arguments have been
      developed for a similar role of C-peptide. The aims of this study were to
      determine whether insulin acts directly on the RBC enzyme and to evaluate the
      effect of C-peptide on Na/K ATPase activity. Thirty-nine C-peptide-negative type
      1 diabetic patients were studied (blood glucose, 11.2 +/- 1.49 mmol/L; hemoglobin
      A1c [HbA1c], 8.9% +/- 0.1%, mean +/- SEM). Blood samples were obtained in the
      morning, before breakfast and insulin injection. Intact and living RBCs were
      resuspended in their own plasma and incubated with or without insulin (50
      microU/mL) or C-peptide (6 nmol/L). Ex vivo by microcalorimetry, the heat
      produced after 1 hour by the enzyme-induced hydrolysis of adenosine triphosphate
      (ATP), was measured in a thermostated microcalorimeter at 37 degrees C. The
      results showed that Na/K ATPase activity was significantly increased by insulin
      (12.4 +/- 0.5 v 15.4 +/- 0.9 mW/L RBCs, P < .05, n = 23) but not by C-peptide
      (11.9 +/- 0.7 v 12.9 +/- 0.9 mW/L RBCs, NS, P = .26, n = 12). In another
      experiment, RBC suspensions were incubated at 37 degrees C in a water bath with
      or without insulin (50 microU/mL) or C-peptide (6 nmol/L) for 10 minutes. RBC
      membranes were isolated and Na/K ATPase activity was assessed by measuring
      inorganic phosphate release at saturating concentrations of all substrates. The
      results showed that insulin and C-peptide significantly increased RBC Na/K ATPase
      activity (342 +/- 25, P < .005 and 363 +/- 30, P < .005, respectively v255 +/- 22
      nmol Pi x mg protein(-1) x h(-1), n = 14). We conclude that insulin and C-peptide
      act directly on RBC Na/K ATPase, thus restoring this activity in type 1 diabetic
      patients. The stimulatory effect of C-peptide observed in vitro on RBC Na/K
      ATPase activity confirms that C-peptide plays a physiological role.

PMID- 10909998
TI  - Characterization of methylaminoisobutyric acid transport by system A in rat
      mammary gland.
AB  - During lactation, the mammary gland has a large demand for amino acids for the
      synthesis of milk proteins and fatty acids. Arteriovenous differences in amino
      acids across the mammary gland show an elevated uptake of small neutral amino
      acids that are mainly transported via system A. The purpose of this study was to
      characterize the transport of methylaminoisobutyric acid (MeAIB), an amino acid
      analog used to model transport by system A in lactating rat mammary gland
      explants. MeAIB accumulation in mammary gland cells increased steadily, and after
      3 hours of incubation, the intracellular concentration of the analog was 8-fold
      higher than the concentration in the medium. MeAIB transport into mammary gland
      explants showed a Km of 3.3 +/- 0.4 mmol/L and a maximal velocity (Vmax) of 555
      +/- 23 pmol/microL intracellular fluid (ICF) x min, indicating a system with high
      capacity but low affinity for its substrate. MeAIB transport into mammary tissue
      depended highly on Na+, and the uptake was inhibited by addition of natural and
      analog small neutral amino acids. Cationic, anionic, and large neutral amino
      acids did not reduce MeAIB transport into mammary gland explants. Preincubation
      of mammary gland explants in an amino acid-free medium stimulated MeAIB
      transport, suggesting an adaptive regulation. The addition of an equimolar
      mixture of alanine, glycine, and serine to the preincubation medium inhibited
      stimulation of MeAIB transport. Furthermore, stimulation of MeAIB uptake by amino
      acid starvation was also prevented by the addition of actinomycin D,
      cycloheximide, tunicamycin, and colchicine. Dibutyryl cyclic adenosine
      monophosphate (cAMP) increased MeAIB uptake, whereas phorbol 12-myristate 13
      acetate (PMA) did not stimulate MeAIB transport. During the first postweaning
      days, kinetic analyses showed a decrease of 27% in the Vmax. Injection of rat
      lactating mammary gland mRNA into Xenopus laevis oocytes induced expression of
      the MeAIB transport system; however, the induction was only 83% above background
      MeAIB uptake. The results of this study provide a partial explanation for the
      formation of the metabolic pool of small neutral amino acids in the lactating
      mammary gland.

PMID- 10909999
TI  - In vivo sequential study of skeletal muscle capillary permeability in diabetic
      rats: effect of anthocyanosides.
AB  - Alterations in the capillary filtration of macromolecules are well documented in
      diabetic patients and experimental diabetes. Various flavonoids including
      anthocyanosides and ginkgo biloba extracts have been shown to be effective
      against experimentally induced capillary hyperfiltration. The aim of the present
      study was to test the effects of anthocyanosides on capillary filtration in
      diabetic rats. For this purpose, we have validated the use of our previously
      described in vivo method for measurement of the capillary filtration of albumin
      (CFA) in rats. Male Wistar rats with streptozotocin (STZ)-induced diabetes were
      randomized in 3 groups to receive either ginkgo biloba (group A), Vaccinium
      myrtillus (group B), or no treatment (group C). The isotopic test of CFA
      consisted of intravenously injecting 99mtechnetium-labeled albumin, inducing
      venous compression on a hindquarter, and measuring radioactivity externally on
      the limb before, during, and after removal of venous compression. After removal
      of the tourniquet, the radioactivity curve decreased. Interstitial albumin
      retention (AR) and the ratio of the amplitudes of the low- and high-frequency
      peaks (LF/HF ratio), an index of lymphatic function obtained by the fast Fourier
      transform of the last part of the radioactivity curve, were calculated. In STZ
      treated animals, the isotopic test was performed at a mean age of 97 days (time
      1) and after 6 weeks (time 2) and 12 weeks (time 3) of treatment, ie, 6 and 12
      weeks after time 1. At time 1, AR was significantly higher in the 3 diabetic
      groups than in the control rats, without a significant difference between these
      groups. In group B, AR decreased significantly (P = .015) at times 2 and 3. In
      group C, AR increased significantly (P < .0005) from time 1 to time 3. In group
      A, AR increased slightly (NS) between time 1 and time 3. In groups A and C, the
      LF/HF ratio significantly increased with time (P < .0005) and the levels at time
      3 were significantly higher versus control rats (P < .0001). In group B, the
      LF/HF ratio remained unchanged from time 1 to time 3 and similar to the values
      found in the control rats. In conclusion, these data show that (1) this new in
      vivo noninvasive method can be used to study CFA in skeletal muscle in diabetic
      rats, (2) it is reproducible and may be repeated over several months to evaluate
      spontaneous microcirculatory changes, and (3) anthocyanosides appear to be
      effective in preventing the increase in CFA and the failure of lymphatic uptake
      of interstitial albumin in diabetic animals.

PMID- 10910000
TI  - Effect of furosemide on the plasma concentration and urinary excretion of purine
      bases, adenosine, and uridine.
AB  - To examine whether furosemide affects the plasma concentration and urinary
      excretion of purine bases, adenosine, and uridine, we administered 20 mg
      furosemide intravenously to 6 healthy subjects. Furosemide decreased the plasma
      concentration of hypoxanthine by 39% and increased plasma renin activity (PRA)
      and the plasma concentration of protein by 3.4-fold and 9%, respectively, at 90
      minutes after administration. Furthermore, it decreased the urinary excretion of
      hypoxanthine, xanthine, and uric acid by 47%, 49%, and 49%, respectively, and the
      fractional clearance of xanthine and uric acid by 44% and 47%, respectively,
      during the 1-hour period between 60 and 120 minutes after administration.
      However, furosemide did not affect the plasma concentration or urinary excretion
      of adenosine and uridine. In addition, in an in vitro incubation study of
      erythrocytes, furosemide (10 microg/mL) did not affect the concentration of
      hypoxanthine in the incubation medium or the activity of erythrocyte purine
      nucleoside phosphorylase and 5'-nucleotidase. These results imply that xanthine
      may share a renal transport pathway with uric acid. Further, it is suggested that
      the furosemide-induced decrease in hypoxanthine may be ascribable to a decrease
      in adenosine triphosphate (ATP) degradation related to the inhibition of chloride
      transport in the body.

PMID- 10910001
TI  - Relationship between plasminogen activator inhibitor-1 antigen, leptin, and fat
      mass in obese children and adolescents.
AB  - Hyperleptinemia may be associated with cardiovascular risk and is linked with
      parameters of fibrinolytic processes in adults. We studied whether body fatness,
      leptin, and insulin interact with plasminogen activator inhibitor-1 antigen (PAI
      1-Ag) and tissue-type plasminogen activator antigen (tPA-Ag) in obese children
      and adolescents. Twenty-three boys (mean +/- SD: age, 10.7 +/- 3.3 years; body
      mass index [BMI], 28.7 +/- 5.4 Kg/m2) and 19 girls (age, 11.9 +/- 2.7 years; BMI,
      29.4 +/- 4.8 Kg/m2) were investigated. Body fat mass (FM) in the children was
      calculated by bioelectrical impedance analysis, and blood samples were obtained
      for leptin, insulin, C-peptide, PAI-1-Ag, and tPA-Ag. The children were divided
      into 3 subgroups according to maturation. Maturity was associated with greater
      adiposity and higher levels of leptin and C-peptide, but insulin and PAI-1-Ag
      were not different between prepubertal, pubertal, and late/postpubertal children.
      PAI-1-Ag was associated with leptin and insulin, but not after adjustment for
      fatness. PAI-1-Ag was independently associated with tPA-Ag (r = .36, P < .02).
      Multiple regression analysis showed that tPA-Ag failed to reach the level of
      significance (P = .07), but FM contributed to the variation in PAI-1-Ag (adjusted
      R2 = .29). The BMI was the main determinant for the variation in leptin (adjusted
      R2 = .386) and in insulin (adjusted R2 = .60, all P < .001). Neither gender,
      maturation, chronological age, or leptin contributed significantly to the
      variation in either PAI-1-Ag or tPA-Ag. Our data suggest that adiposity and other
      variables contribute to higher levels of PAI-1-Ag. Leptin seems not to be
      independently linked with fibrinolytic parameters, but an unfavorable metabolic
      and fibrinolytic risk profile might emanate from the obese pubertal stage.

PMID- 10910002
TI  - Assessment of insulin secretion in relatives of patients with type 2 (non-insulin
      dependent) diabetes mellitus: evidence of early beta-cell dysfunction.
AB  - To examine beta-cell function in glucose-tolerant offspring of type 2 diabetic
      families, 41 insulin-resistant (hyperinsulinemic-euglycemic clamp, P < .001)
      first-degree relatives and 32 controls underwent oral (OGTT) and intravenous
      (IVGTT) glucose tolerance tests and a constant intravenous glucose infusion (4.0
      or 4.5 mg/kg/min) with blood sampling every minute for insulin determinations.
      Insulin concentration time-series were analyzed with complementary mathematical
      models (deconvolution and autocorrelation analysis, approximate entropy [ApEn],
      and coefficient of variation [CV] for a 6-point moving average, together with a
      combined index for regularity and stationarity [RaS] based on the last 2
      measures). During the OGTT, the area under the curve (AUC) for plasma glucose was
      moderately (11%) but significantly (P < .01) elevated in the relatives despite a
      trend for increased serum insulin (AUC, P = .14). The acute-phase serum insulin
      response (IVGTT) did not differ between groups (2,055 +/- 330 v 1,766 +/- 229
      pmol/L x 10 min, P = .84) but was inappropriately low (individually, P < .05 v
      control group) for the degree of insulin resistance in 16 relatives.
      Deconvolution analysis of the insulin time-series did not uncover differences in
      either the intersecretory pulse interval (5.8 +/- 0.2 v5.7 +/- 0.2 min/pulse) or
      the fractional secretory burst amplitude (133% +/- 10% v 116% +/- 7% over basal)
      between the 2 groups. Similarly, significant autocorrelation coefficients were
      observed in a comparable number of relatives and control subjects (P = .74). In
      contrast, the RaS index was significantly higher (ie, insulin time-series was
      more irregular and nonstationary) in the relatives (0.221 +/- 0.194) than in the
      controls (-0.318 +/- 0.176, P < .05), primarily attributed to the pattern of
      insulin secretion in relatives with a strong genetic burden. In conclusion,
      nonstationary and disorderly insulin secretion patterns during glucose
      stimulation and a low acute-phase serum insulin response associated with
      significant insulin resistance suggest early beta-cell regulatory dysfunction in
      individuals genetically predisposed to type 2 diabetes mellitus prior to any
      evident alterations in insulin secretory burst frequency or mass.

PMID- 10910003
TI  - Regulation of lipoprotein lipase and hormone-sensitive lipase activity and gene
      expression in adipose and muscle tissue by growth hormone treatment during weight
      loss in obese patients.
AB  - It is well known that growth hormone (GH) treatment reduces fat mass (FM), which
      presumably is mediated through stimulation of triglyceride breakdown and
      inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). However, it is
      unknown which of the 2 GH-regulated pathways are of most importance for the
      reduction in FM. We investigated the effect of weight loss together with GH
      treatment on the activity and gene expression of LPL and hormone-sensitive lipase
      (HSL) in AT and muscle tissue. A very-low-calorie diet ([VLCD] 740 kcal/d) was
      given to 18 obese women (body mass index [BMI] > 35 kg/m2) and half of them were
      treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo
      controlled study. Subcutaneous fat and muscle biopsies were taken before and
      after 4 weeks. Weight loss after 4 weeks was similar in the 2 groups, with a
      reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0%
      ([NS] nonsignificant). The weight loss resulted in a small and NS reduction of AT
      LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was
      significantly reduced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was
      not affected by the weight loss alone, but a significant reduction was observed
      in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly
      enhanced after weight loss, but GH had no additional effect on this minor
      increment. This is in accordance with the finding that the increment in free
      fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was
      associated with a significant reduction of high-density lipoprotein (HDL)
      cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL activity
      but had no additional effect on the hypocaloric-induced loss of FM, indicating
      that under such circumstances, AT-LPL does not directly regulate adipose tissue
      mass. GH was not found to have opposite effects on the activity of LPL in adipose
      tissue and muscle, since GH treatment reduced them both (by 65% and 20%,
      respectively). The VLCD-induced weight loss was associated with a minor enhanced
      activity of AT-HSL with no independent effect of GH. Thus, concerning body
      weight, FM, and lipolytic activity, treatment with GH offers no extra benefits
      during a VLCD for 4 weeks.

PMID- 10910004
TI  - Long-term administration of highly purified eicosapentaenoic acid ethyl ester
      prevents diabetes and abnormalities of blood coagulation in male WBN/Kob rats.
AB  - We investigated the effect of long-term administration of highly purified
      eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid, on
      the development of diabetes, insulin resistance, and abnormalities of blood
      coagulation in male WBN/Kob rats, a model of spontaneous diabetes mellitus. After
      8-month oral EPA-E treatment, the incidence of diabetes at a dose of 0.1, 0.3,
      and 1.0 g/kg was 92%, 50%, and 17%, respectively. Its incidence was suppressed
      significantly and dose-dependently at a dose of 0.3 g/kg or higher compared with
      the rate (100%) for the vehicle control. Additionally, EPA-E significantly and
      dose-dependently decreased the elevation of plasma glucose after an oral glucose
      load and increased the glucose infusion rate (GIR) during the euglycemic insulin
      glucose clamp test at a dose of 0.1 g/kg or higher compared with the vehicle
      control. Furthermore, EPA-E significantly and dose-dependently ameliorated
      coagulation-related parameters, including the prothrombin time (PT), activated
      partial thromboplastin time (APTT), fibrinogen level, and factor II, V, VII,
      VIII, IX, X, XI, and XII and antithrombin III (AT III) activities, and
      fibrinolysis-related parameters, including plasminogen, tissue-type plasminogen
      activator (t-PA), alpha2-plasmin inhibitor (alpha2-PI), and plasminogen activator
      inhibitor (PAI), and also suppressed ADP- or collagen-induced platelet
      aggregation and the cholesterol to phospholipid (C/P) molar ratio in platelet
      membranes at a dose of 0.1 g/kg or higher. These data demonstrate multiple
      actions of the product in these laboratory animals. These include changes in
      platelet function, coagulation/fibrinolysis factors, plasma immunoreactive
      insulin secretion, and plasma glucose/insulin resistance.

PMID- 10910005
TI  - Involvement of bradykinin in acute exercise-induced increase of glucose uptake
      and GLUT-4 translocation in skeletal muscle: studies in normal and diabetic
      humans and rats.
AB  - Acute exercise induces glucose uptake in skeletal muscle in vivo, but the
      molecular mechanism of this phenomenon remains to be identified. In this study,
      we evaluated the involvement of bradykinin in exercise-induced glucose uptake in
      humans and rats. In human studies, plasma bradykinin concentrations increased
      significantly during an ergometer exercise (20 minutes) in 8 healthy
      normoglycemic subjects and 6 well-controlled type 2 diabetic patients (mean
      hemoglobin A1c [HbA1c], 6.4% +/- 0.6%), but not in 6 poorly controlled type 2
      diabetics (mean HbA1c, 11.6% +/- 2.6%). In rat studies, plasma bradykinin
      concentrations also significantly increased after 1 hour of swimming in
      nondiabetic and mildly diabetic (streptozotocin [STZ] 45 mg/kg intravenously
      [IV]) rats, but not in rats with severe diabetes (STZ 65 mg/kg IV). Glucose
      influx (maximum velocity [Vmax]) and GLUT-4 translocation in skeletal muscle of
      nondiabetic rats significantly increased after 1 hour of swimming, but these
      increases were abrogated by subcutaneous infusion of bradykinin B2 receptor
      antagonist HOE-140 (400 microg x kg(-1) x d(-1)). Insulin-stimulated tyrosine
      phosphorylation and phosphatidylinositol (PI) 3-kinase activity in response to
      insulin injection (20 U/kg IV) in the portal vein were significantly attenuated
      in exercised rats pretreated with HOE-140 compared with saline-treated exercised
      rats. Our results suggest that plasma bradykinin concentrations increase in
      response to acute exercise and this increase is affected by blood glucose status
      in diabetic patients. Moreover, the exercise-induced increase in bradykinin may
      be involved in modulating exercise-induced glucose transport through an increase
      of GLUT-4 translocation, as well as enhancement of the insulin signal pathway,
      during the postexercise period in skeletal muscle, resulting in a decrease of
      blood glucose.

PMID- 10910006
TI  - Lipolysis and lipid oxidation in weight-losing cancer patients and healthy
      subjects.
AB  - Increased lipolysis has been suggested as one of the possible mechanisms
      underlying cancer cachexia. The study aim was to assess whether lipolysis is
      increased in weight-losing cancer patients, considering their differences in food
      intake and body composition. Sixteen healthy subjects and 18 cancer patients with
      different tumor types and a weight loss of at least 5% in the previous 6 months
      were included in the study. Food intake was recorded for 4 days. After an
      overnight fast, [1,1,2,3,3-2H5]glycerol was infused to determine the rate of
      appearance (Ra) of glycerol as a measure of whole-body lipolysis, and [1
      13C]palmitic acid was infused to determine the Ra of palmitate as a measure of
      adipocyte fatty acid release. Palmitate oxidation was determined by measuring
      13CO2 enrichment in breath samples, and body composition was measured by
      bioelectrical impedance analysis. After adjustment for energy intake, whole-body
      lipolysis was significantly higher in cancer patients versus healthy subjects
      (6.46 +/- 0.63 and 4.67 +/- 0.46 micromol/kg +/- min, respectively, P < .05). The
      difference in adipocyte fatty acid release did not reach statistical
      significance. The rate of palmitate oxidation was also significantly higher in
      patients than in healthy subjects (1.15 +/- 0.10 and 0.93 +/- 0.07 )micromol/kg x
      min, respectively, P < .05). No differences in body composition were observed
      between groups. In conclusion, whole-body lipolysis (as measured by the Ra of
      glycerol) and palmitate oxidation were elevated in weight-losing cancer patients,
      but fatty acid release was not significantly different.

PMID- 10910007
TI  - Reversal of type 2 diabetes in mice by products of malaria parasites: I. Effect
      of inactivated parasites.
AB  - C57BL/KsJ-db/db and C57BL/KsJ-ob/ob mice are good models for studies on human
      obesity and type 2 diabetes. We have previously shown that infection with blood
      stage malaria or injection of extracts from malaria-parasitized red blood cells
      induces hypoglycemia in normal mice and normalizes hyperglycemia in mice made
      moderately diabetic by streptozotocin. In the present study, we show that a
      single intravenous (IV) injection of Formalin-fixed Plasmodium yoelii YM (FFYM)
      preparation decreases blood glucose in db/db mice from an initial value of 19
      mmol/L to a normal value of 7 mmol/L (P < .0001) for at least 24 hours and
      reduces food intake. Plasma insulin concentrations in db/db mice were not
      altered. FFYM was also active in normal and ob/ob mice, an effect associated with
      an increase in plasma insulin. Although the rate of weight gain in lean ob/+ and
      lean db/+ was not altered by this treatment, there was a significant reduction in
      weight gain in db/db and ob/ob mice (P < .001). We suggest that malaria-derived
      molecules, when fully characterized, may provide structural information for the
      development of new agents for the management of type 2 diabetes.

PMID- 10910008
TI  - Platelet function in patients with familial hypertriglyceridemia: evidence that
      platelet reactivity is modulated by apolipoprotein E content of very-low-density
      lipoprotein particles.
AB  - We evaluated platelet function in patients with familial hypertriglyceridemia
      (FHTG). Compared with healthy gender-matched controls, platelets from patients
      showed lower aggregation (P < .01) and thromboxane formation (P < .01) in
      response to collagen. Very-low-density lipoprotein (VLDL) particles obtained from
      the patients inhibited collagen-induced aggregation, whereas VLDL particles from
      controls had opposite effects. The VLDL-induced effect was regulated by its
      apolipoprotein E (apoE) content. Indeed, apoE-VLDL-rich fractions caused
      antiaggregative effects, whereas apoE-VLDL-poor fractions produced a strong
      proaggregative response. Since we have recently demonstrated that VLDL particles
      may regulate the activity of platelet low-density lipoprotein (LDL) receptor by a
      phenomenon of downregulation and desensitization, in this study, we have
      investigated the effect of prolonged exposure to circulating VLDL levels on the
      activity of platelet LDL receptor by a double-blind controlled study with
      gemfibrozil (600 mg twice daily) in 18 subjects with FHTG. Platelets from
      patients exhibited fewer platelet LDL receptors and 125I-LDL binding was
      saturable at a lower protein concentration. After 6 months, gemfibrozil therapy
      versus placebo had a marked lipid-lowering effect, significantly decreased
      triglycerides (61%), VLDL cholesterol (72%), apoB (28%), and apoE (55%), and
      increased high-density lipoprotein (44%) and apoA-I (18%). Furthermore,
      gemfibrozil affected the apoprotein composition of VLDL: total protein increased
      by 28%, the molar ratio of apoE to apoB decreased 64%, and apoE content decreased
      55%. However, no differences in phospholipid, triglyceride, or total cholesterol
      were detected. Moreover, platelet function was markedly altered by gemfibrozil
      therapy. Collagen-induced aggregation and thromboxane formation were
      significantly enhanced (P < .01). The initial antiaggregative pattern of VLDL
      particles was changed to a significant proaggregative effect (P < .01), and the
      number of LDL binding sites was markedly upregulated (P < .001). Both receptor
      upregulation and the change in the aggregative effect of VLDL particles were
      associated with the reduction of apoE content in VLDL particles (P < .05). The
      overall results indicate that in the regulation of platelet reactivity in
      hypertriglyceridemic patients, apoE content of VLDL particles and their
      interaction with the platelet LDL receptor are involved.

PMID- 10910009
TI  - Comparison of the inhibitory effect of insulin and hypoglycemia on insulin
      secretion in humans.
AB  - Although both insulin and hypoglycemia are known to inhibit endogenous insulin
      secretion, their potency to suppress insulin secretion has not been directly
      compared thus far. The serum C-peptide concentration was measured during 28
      euglycemic and 28 stepwise hypoglycemic (4.1,3.6, 3.1, and 2.6 mmol/L) clamp
      experiments using either a low-rate (1.5 mU x min(-1) x kg(-1)) or high-rate
      (15.0 mU x mU(-1) x kg(-1)) insulin infusion. The experiments lasted 6 hours and
      were performed in 28 lean healthy men. During both the euglycemic and
      hypoglycemic clamps, serum insulin was approximately 40-fold higher during the
      high-rates versus low-rate insulin infusion (euglycemia, 24,029 +/- 1,595 v 543
      +/- 34 pmol/L; hypoglycemia, 23,624 +/- 1,587 v 622 +/- 32 pmol/L). Under
      euglycemic conditions, serum C-peptide decreased from 0.54 +/- 0.04 to 0.41 +/-
      0.05 nmol/L during the low-rate insulin infusion (P < .05) and from 0.55 +/- 0.07
      to 0.27 +/- 0.09 nmol/L during the high-rate insulin infusion (P < .001). Under
      hypoglycemic conditions, serum C-peptide decreased from 0.50 +/- 0.03 to 0.02 +/-
      0.01 nmol/L during the low-rate insulin infusion (P< .001) and from 0.46 +/- 0.07
      to 0.02 +/- 0.01 nmol/L during the high-rate insulin infusion (P< .001). In the
      euglycemic clamp condition, the high-rate insulin infusion reduced the C-peptide
      concentration more than the low-rate insulin infusion (P < .05). Independent of
      the rate of insulin infusion, the decrease in C-peptide was distinctly more
      pronounced during hypoglycemia versus euglycemia (P < .001). These data indicate
      that insulin inhibits insulin/C-peptide secretion in a dose-dependent manner.
      Hypoglycemia is a much stronger inhibitor of insulin secretion than insulin
      itself.

PMID- 10910010
TI  - Exercise training prevents maturation-induced decreases in insulin receptor
      substrate-1 and phosphatidylinositol 3-kinase in rat skeletal muscle.
AB  - We have previously reported that exercise training prevents a maturation-induced
      decrease in insulin sensitivity and suggested that an improvement of insulin
      sensitivity by exercise training was attributable, in part, to an increase in
      insulin-sensitive GLUT-4 on the skeletal muscle plasma membrane. In this study,
      we examined the effects of maturation and exercise training on the gene
      expression and protein content of the components of post-insulin receptor signal
      transduction in rat skeletal muscle. Rats aged 3 weeks were sedentary or trained
      by voluntary running through 4 or 27 weeks of age, and then the rats in both the
      sedentary and trained groups were killed and the gastrocnemius muscle was
      immediately removed for analysis of mRNA and protein content. The concentration
      of mRNA and protein for insulin receptor substrate-1 (IRS-1) in sedentary rats
      significantly decreased with maturation (49% and 63%, respectively, at age 27
      weeks v age 4 weeks), but in trained rats they did not decrease with maturation.
      Although the level of phosphatidylinositol 3-kinase (PI 3-kinase) mRNA in
      sedentary rats was not altered with maturation, PI 3-kinase protein in sedentary
      rats significantly decreased with maturation (73% at 27 weeks v 4 weeks).
      However, PI 3-kinase protein in trained rats did not decrease with maturation.
      These results suggest that the prevention of maturation-induced decreases in the
      protein content of IRS-1 and PI 3-kinase is involved in the mechanisms
      responsible for the improvement of insulin sensitivity by exercise training, and
      exercise training may affect transcriptional regulation of the IRS-1 gene and
      posttranscriptional regulation of PI 3-kinase expression.

PMID- 10910011
TI  - Introduction. Norepinephrine: neurotransmitter for the millennium.

PMID- 10910012
TI  - Problems with currently available antidepressants.
AB  - Although options for pharmacologic treatment for depression have grown seemingly
      exponentially over the past several decades, the current armamentarium of
      antidepressants continues to have limitations of both efficacy and tolerability.
      The problems include an unacceptable lack of efficacy, delayed onset of
      therapeutic effects, an inability to predict responses to one or another agent,
      drug-drug interactions, and difficulty with tolerability during both acute and
      chronic treatment. This article reviews the problems that persist in the use of
      currently available antidepressant medications and presents a list of attributes
      that would be characteristic of the ideal antidepressant.

PMID- 10910013
TI  - Norepinephrine dysfunction in depression.
AB  - The study of the noradrenergic neurotransmitter system remains one of the
      cornerstones of depression research. Better understanding of the action of
      norepinephrine and other catecholamines at the synaptic and intracellular level
      holds the potential for providing clues to the etiology of depression and
      introduces exciting possibilities for the development of novel medications for
      the treatment of depression. The following review of norepinephrine as it relates
      to depression will shed light on the current understanding of the noradrenergic
      system and the role for selective norepinephrine reuptake inhibitors (selective
      NRIs) in the treatment of depression.

PMID- 10910014
TI  - Norepinephrine involvement in antidepressant action.
AB  - Because of the introduction and popularity of the selective serotonin reuptake
      inhibitor (SSRI) antidepressants, much attention was centered on the
      indolealkylamine 5-hydroxytryptamine, or serotonin. To some extent, this focus on
      serotonin occurred at the expense of the catecholamine neurotransmitter
      norepinephrine. Nevertheless, it has been apparent for almost 40 years that
      selective blockers of norepinephrine reuptake may be antidepressants (e.g.,
      desipramine). This brief review covers the acute pharmacologic effects that may
      be responsible for the efficacy of currently marketed antidepressants as well as
      that of reboxetine, a newly developed selective norepinephrine reuptake
      inhibitor. Also discussed is the fact that the acute pharmacologic profile of
      selective reuptake inhibitors often predicts effects they produce when given long
      term. For example, the long-term administration of SSRIs produces certain effects
      on serotonergic systems, but not noradrenergic ones. By contrast, selective
      norepinephrine reuptake inhibitors, when given long term, modify certain
      noradrenergic parameters, but not serotonergic indices. Finally, it is speculated
      how drugs that enhance central noradrenergic transmission might ameliorate the
      symptoms of depression.

PMID- 10910016
TI  - Plasma exchange for acute attacks of demyelinating disease: detecting a Lazarus
      effect.

PMID- 10910015
TI  - Clinical efficacy of reboxetine in major depression.
AB  - The past decade has witnessed the advent of selective serotonin reuptake
      inhibitors (SSRIs) as first-line treatments for major depression. Still, there is
      considerable debate as to whether these agents are as effective or as potent as
      the first-generation tricyclic antidepressants (TCAs) or the mixed reuptake
      inhibitor, venlafaxine, all of which exert considerable effect on norepinephrine
      (NE) reuptake. Recently, reboxetine, a selective NE reuptake inhibitor (selective
      NRI), has been introduced in Europe. This drug has only a minimal affinity for
      muscarinic acetylcholine receptors and therefore causes less dry mouth,
      constipation, or other such effects than do the TCAs. Reboxetine does not block
      serotonin reuptake or alpha1 receptors and, thus, does not appear to produce
      significant nausea, diarrhea, or hypotension. Unlike other antidepressants,
      reboxetine appears to be nonsedating. Data on acute and long-term clinical
      efficacy and safety from double-blind, placebo-controlled, and active comparator
      studies with reboxetine are reviewed. These studies indicate that reboxetine is
      significantly more effective than placebo and as effective as fluoxetine in
      reducing depressive symptoms. Improvements in social adjustments were reported to
      be more favorable with reboxetine than with fluoxetine. Further, data from
      controlled clinical trials have shown that the side effect profile for reboxetine
      is relatively benign. The clinical implications of studies on reboxetine are
      discussed with an eye toward understanding the potential role NE reuptake
      blockers may play in the treatment of patients with major depression.

PMID- 10910017
TI  - Ethical lessons learned from the use of therapeutic plasma exchange in neurologic
      disease.
AB  - Conflicts of interest are inherent in the practice of medicine, particularly in
      the conduct of clinical research. Such conflicts can often be identified and even
      resolved by the application of ethical principles as an integral part of such
      research. The opportunity to participate in a series of controlled clinical
      trials of therapeutic plasma exchange (TPE) in diverse neurologic disease
      provided an insight into some of the ethical dilemmas posed by such conflicts of
      interest. Chief among these was the recognition that informed consent is a
      precious though fragile and multidimensional concept. In the last analysis,
      ethics is the "business of being human"; respect for its guidance helps to ensure
      the success of clinical research.

PMID- 10910018
TI  - Immunoadsorption in Guillain-Barre syndrome and myasthenia gravis.
AB  - Elimination of circulating antibodies by hemapheresis is an empirical treatment
      concept in various neuroimmunological diseases. Plasma exchange (PE) has been
      shown to be superior to symptomatic treatment in Guillain-Barre syndrome (GBS) in
      two large multicenter studies. It is also effective in myasthenia gravis (MG),
      although no comparative studies have been performed. Immunoadsorption (IA) using
      polyvinyl alcohol gel columns to which phenylalanin (IM-PH) or tryptophan (IM-TR)
      are covalently bound is an alternative to PE, and seems to have equal efficacy
      and comparable side effects. This method also obviates the need for replacement
      of plasma with human albumin or plasma. We compared the treatment results of 11
      patients with GBS treated by PE to those of 13 patients treated by IA using an IM
      TR column. Here, we found no statistically significant differences with regard to
      efficacy and clinical or procedural complications. From these data we conclude
      that immunoadsorption can be used as an equal alternative to PE. A large
      multicenter study comparing PE, intravenous immunoglobulins (IVIG), and the
      combination of both in the treatment of GBS revealed no significant difference
      between the 3 treatment groups. In MG, only 2 small studies have been performed
      using IA, and no studies comparing PE or other treatments to IA have been
      conducted. Both investigations of IA therapy demonstrated a marked reduction in
      the acetylcholine receptor (AchR) antibodies and a sustained improvement of the
      clinical signs. These results therefore show that IA is an effective treatment
      for myasthenia gravis.

PMID- 10910019
TI  - Apheresis and selective adsorption plus immunoglobulin treatment in Guillain
      Barre syndrome.
AB  - Plasma exchange (PE) and administration of intravenous immunoglobulin (i.v. IgG)
      are established treatments for Guillain-Barre syndrome (GBS). Combination
      treatment with elimination of postulated pathogenetic factors by PE or selective
      adsorption (SA) treatment and subsequent immunomodulation by intravenous IgG may
      provide a more effective treatment. In a single-center randomized study, 45
      patients with acute GBS were prospectively examined using a clinical score. We
      treated 11 patients by PE, 13 with SA using a tryptophan-linked polyvinyl alcohol
      gel adsorbent, and 21 with SA followed by intravenous IgG. The patients treated
      sequentially by selective adsorption and intravenous IgG improved significantly
      better than the patients who received plasma treatment only. The results suggest
      that combination treatment of GBS may be superior to plasma treatment alone.

PMID- 10910020
TI  - Therapeutic apheresis for cancer related hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) can be seen as a result of disseminated cancer,
      as a consequence of chemotherapy, or in association with bone marrow
      transplantation (BMT). Further distinction can be made when the clinical
      presentation is that of an acute, fulminant course with rapidly progressive renal
      failure or that of a sub-acute form with a slow progression of renal involvement.
      Each of the different etiologies (cancer, chemotherapy, or BMT) and each of the
      two basic clinical presentations has its own prognosis. There are no randomized,
      controlled studies to elucidate the role of therapeutic apheresis for cancer
      related HUS. Hemolytic uremic syndrome related to disseminated cancer is most
      often a terminal event and is not commonly treated with apheresis procedures,
      although there are anecdotal reports that plasma exchange may be beneficial.
      Chemotherapy and drug-related HUS have a prognosis that is strongly dependent on
      the severity of the presentation, but even in the most severe cases may respond
      to either immunoadsorption or plasma exchange with fresh frozen plasma (FFP).
      Finally, BMT-related HUS has a poor prognosis but may respond to
      immunoadsorption, plasma exchange, or a combination of the two.

PMID- 10910022
TI  - Therapeutic apheresis application using membrane plasma fractionation technology:
      present scope and limitations.
AB  - Membrane technologies have been applied for therapeutic apheresis, such as plasma
      separation and plasma fractionation. Membrane used for plasma fractionation has a
      microporous structure with pore sizes in the range of 0.01-0.04 microm. A
      membrane plasma fractionator is utilized for the second filter in the double
      filtration plasmapheresis (DFPP) system and is applied for treatment of various
      diseases. This article summarizes the present scope and limitation of membrane
      plasma fractionation.

PMID- 10910021
TI  - Apheresis registry in France: indications, techniques, and complications. French
      Registry Study Group.
AB  - The French Registry for Plasma Exchange (PE) was set up in 1985. For 13 years it
      has allowed for the analysis of the techniques used, along with the indications
      and complications. After a decrease in the number of participating centers due to
      the heaviness of the data collection mode, the telematic network created in 1991
      led to a new increase in participants from 26 in 1990 to 69 in 1998. Follow-up
      shows a slight fall in activity since some protocols ended, while the
      neurological pathologies remain the most frequent indicators. The important
      modifications observed over the years are the increase of the centrifugation
      technique, the development of plasma treatment, and the plasma substitution by an
      association of albumin-pentastarch. The French Registry for plasma exchange is
      the largest data base dealing with therapeutic hemapheresis. The registry set-up
      through the internet is the first step toward an international data base.

PMID- 10910023
TI  - Low density lipoprotein apheresis in treatment of hyperlipidemia: experience with
      four different technologies.
AB  - The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes
      combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD)
      refractory to diet and lipid lowering drugs is poor. A new therapeutic option for
      such patients is regular treatment with low density lipoprotein (LDL) apheresis.
      In total 33 patients (16 males, 17 female, aged 43.8+/-14.3 years), suffering
      from severe HLP resistant to diet and lipid lowering drugs, were treated for
      62.3+/-21.3 (range, 1-113) months with LDL-apheresis. Four different LDL
      apheresis systems were used: the dextran sulfate adsorption for 28 of 33
      (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter,
      Germany), LDL-hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the
      immunoadsorption system with special antilipoprotein (a) columns for 1 of 33
      patients (Lipopak, Pocard, Russia). Before applying LDL-apheresis, 27 of 33
      patients suffered from CHD with severe angina pectoris symptoms, a history of
      myocardial infarction or coronary artery venous bypass (CAVB). With LDL
      apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28%
      for Lp(a), and 38% for triglycerides were reached. Severe side-effects, such as
      shock or allergic reactions, were very rare (0.5%). In the course of treatment an
      improvement in general well-being and increased performance were experienced in
      29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to
      100% of nitrate medication was observed. Regarding the different apheresis
      systems used, there were no significant differences with respect to the clinical
      outcome and concerning total cholesterol, LDL, HDL, and triglyceride
      concentrations. But, in respect to elevated lipoprotein (a) levels, the
      immunoadsorption method using special anti-lipoprotein (a) columns seems to be
      the most effective (-57% versus -25% [Kaneka, p < 0.05] or -23% [Baxter, p <
      0.05]). The present data clearly demonstrate that treatment with LDL-apheresis in
      patients suffering from severe HLP, refractory to maximum conservative therapy,
      is effective and safe in long-term application.

PMID- 10910024
TI  - Push-pull sorbent-based pheresis and hemodiabsorption in the treatment of hepatic
      failure: preliminary results of a clinical trial with the BioLogic-DTPF System.
AB  - The BioLogic-DTPF System combines hemodiabsorption (the BioLogic-DT System with
      dialysis against powdered sorbent) with push-pull sorbent-based pheresis (the
      BioLogic-PF System with powdered sorbent surrounding plasma filters). At blood
      flow rates of 200 ml/min, the system clears creatinine and aromatic amino acids
      at 120-160 ml/min, unconjugated bilirubin at 20-40 ml/min, and cytokines at 15-25
      ml/min. This article outlines a study of the DTPF System in treatment of patients
      with hepatic failure with Grade 3 or 4 encephalopathy and respiratory and kidney
      insufficiency. Treatment appeared to be safe, and there are no significant
      hematologic changes. Physiologic changes include improved blood pressure and
      encephalopathy and stable urine output. Chemical changes include decrease in
      plasma levels of bilirubin, aromatic amino acids, ammonium, creatinine, and
      interleukin-3 (IL-1beta). The BioLogic-DT System is now marketed for treatment of
      acute hepatic failure with encephalopathy. The BioLogic-DTPF System adds the
      capability of removing bilirubin and other strongly protein-bound toxins from
      treated patients and may be of clinical benefit in management of patients with
      the most severe hepatic failure and encephalopathy.

PMID- 10910025
TI  - Neutrophil activation in immunoadsorption.
AB  - Immunoadsorption therapy (IAT) is used in the treatment of autoimmune diseases.
      Although IAT has been reported to modify humoral immunity by inducing chemokines
      and activating complements, much remains unknown about the biological effects of
      IAT on cellular components in peripheral blood. To define the influence of IAT on
      leukocytes, we determined leukocyte L-selectin (CD62L) and Mac-1 (CD11b) as
      parameters for activation of leukocytes in peripheral blood during IAT.
      Peripheral leukocyte L-selectin and Mac-1 were determined continuously by flow
      cytometry in 6 patients with neuroimmunological disorders in whom IAT was
      conducted using a Plasma Flow OP-05 (Asahi Medical Corp., Tokyo, Japan) as a
      plasma separator and Immusorba TR-350 (Asahi Medical Corp., Tokyo, Japan) as an
      adsorption column. Expression of neutrophils (PMN) L-selectin was decreased 30
      min after starting IAT, with the decreases particularly marked at the end of IAT,
      while expression of mononuclear cells (MNC) L-selectin slightly increased during
      IAT. Expression of PMN Mac-1 was markedly increased at the end of IAT, whereas
      expression of MNC Mac-1 did not change during IAT. Leukocyte counts decreased 30
      min after starting IAT, and then increased to the initial level or higher in
      parallel with L-selectin downregulation and Mac-1 upregulation on PMN. L-selectin
      downregulation and Mac-1 upregulation on PMN suggested that activation of PMN
      associated with changes in peripheral leukocyte counts occurred during IAT and
      might play some role in modulating the human circulating blood and immune
      systems.

PMID- 10910026
TI  - Immunoadsorption in dilated cardiomyopathy.
AB  - The prognosis for patients suffering from advanced stages of dilated
      cardiomyopathy (DCM) is poor. Recent studies have shown that immunoadsorption
      (IA) may represent an effective alternative therapeutic approach for other kinds
      of autoimmune diseases with circulating autoantibodies. The objective of this
      pilot study was to ascertain the short-term hemodynamic effects of IA in patients
      with idiopathic DCM and circulating autoantibodies. Our study included 9 patients
      with circulating beta1-adrenoreceptor antibodies who suffered from idiopathic DCM
      as well as severe heart failure (left ventricular ejection fraction <30%).
      Immunoadsorption was performed on 5 consecutive days using an adsorber against
      immunoglobulins (Ig Therasorb, Baxter, Unterschleissheim, Germany). Substitution
      of 0.5 g/kg of polyclonal immunoglobulin took place after the final IA session.
      During IA, the cardiac index and stroke volume index increased from 2.0+/-0.42 to
      2.9+/-0.79 L/min(-1)/m(-2), p < 0.01, and from 24.0+/-7.4 to 35.9+/-10.3 ml/m2, p
      < 0.05, respectively. In addition to drug therapy, IA may represent a promising
      alternative therapeutic possibility for hemodynamic stabilization of patients
      with severe idiopathic DCM.

PMID- 10910027
TI  - The role of immunoadsorption using dextran-sulfate cellulose columns in the
      treatment of systemic lupus erythematosus.
AB  - Immunoadsorption using dextran sulfate (DS)-cellulose columns is reviewed. An
      extracorporeal selective adsorption system using such columns has been developed
      and clinically used to remove anti-DNA from the circulating blood of systemic
      lupus erythematosus (SLE) patients. These columns can adsorb pathogenic anti-DNA
      subgroups of high avidity and/or cationic antibodies, anticardiolipin, anti
      CLbeta2GPI, and anaphylatoxins. An open clinical study on 19 SLE cases (the mean
      number of apheresis sessions totaled 3.7 times; the mean dose of prednisolone, 38
      mg/day) revealed that the mean SLE disease activity index (SLEDAI) score
      significantly decreased from the pretreatment level of 10.2 to 4.5 after
      treatment. Several case reports have indicated that this modality might also be
      useful for treating patients with antiphospholipid syndrome. Compartment model
      analyses showed the one-compartment model to be the most suitable for the
      kinetics of anti-DNA during and following the apheresis procedure. The
      indications for immunoadsorption in the treatment of SLE remain controversial. A
      steroid-sparing effect might be one of them, but further controlled studies are
      necessary to verify this hypothesis.

PMID- 10910028
TI  - Influence of atorvastatin versus simvastatin on fibrinogen and other
      hemorheological parameters in patients with severe hypercholesterolemia treated
      with regular low-density lipoprotein immunoadsorption apheresis.
AB  - Low-density lipoprotein (LDL) apheresis is a treatment option in patients with
      coronary artery disease and elevated LDL cholesterol concentrations if maximal
      drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is
      more effective when combined with strong lipid-lowering drugs, such as
      atorvastatin. However, conflicting data have been published concerning the effect
      of atorvastatin on fibrinogen concentration. Therefore, we investigated the
      effect of atorvastatin compared to simvastatin on fibrinogen concentration and
      other hemorheological parameters in patients treated by weekly LDL apheresis.
      Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male,
      54.0+/-8.9 years) with coronary artery disease treated by weekly LDL
      immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and
      once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma
      and blood viscosity at different shear rates, parameters of red cell aggregation
      at stasis and shear rate 3/s, and erythrocyte filterability were determined 7
      days after the last LDL apheresis after each drug had been given for a minimum
      for 8 weeks. Fibrinogen concentration did not show any statistically significant
      difference during therapy with atorvastatin (3.09+/-0.36 g/L) compared to
      simvastatin (3.13+/-0.77 g/L). Plasma and blood viscosity as well as erythrocyte
      filterability were also unchanged. The increase in red cell aggregation at stasis
      during atorvastatin treatment (5.82+/-1.00 U versus 4.89+/-0.48 U during
      simvastatin; p < 0.05) was inversely correlated with a lower high-density
      liprotein (HDL) cholesterol concentration (1.17+/-0.21 mmol/L versus 1.31+/-0.30
      mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to
      lower concentrations during atorvastatin (4.14+/-0.61 mmol/L versus 4.56+/-0.66
      mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated
      (3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin;
      p < 0.05). In conclusion, fibrinogen concentration and other hemorheological
      parameters were unchanged during atorvastatin compared to simvastatin therapy
      with the exception of a higher red cell aggregation at stasis. Therefore, with
      respect to hemorheology, we conclude that atorvastatin should not be withheld
      from hypercholesterolemic patients regularly treated with LDL immunoadsorption.

PMID- 10910029
TI  - Temporary vascular access for extracorporeal therapies.
AB  - Central venous catheters provide at the present time the basic and ideal method
      to perform acute extracorporeal blood purification. Rapid launch of
      extracorporeal therapy is indicated in two situations: first, renal conditions
      presenting as a recognized acute organic renal failure (ARF) and acute
      decompensation of end stage renal disease (ESRD) without permanent vascular
      access; second, non-renal conditions presenting as urgent clinical situations
      requiring isolated ultrafiltration for chronic congestive heart failure,
      plasmapheresis or selective immunoadsorption for immune diseases, cytapheresis
      for hematological disease, and selective detoxification for certain types of
      poisoning. Central venous catheters are classified into 2 categories according to
      the duration of use: temporary catheter (less than 90 days) and permanent
      catheter (more than 90 days). A temporary catheter, including rigid
      (polyethylene, teflon) and semirigid (polyurethane) material, is indicated in
      emergency situations and for short-term use. A permanent catheter, made usually
      of soft silicone rubber with a subcutaneous anchoring system, has a subcutaneous
      tunnel and is indicated in medium and long-term use. Catheter design has
      benefited greatly from technical advances and material hemocompatability.
      However, catheter-related morbidity still remains high and is associated with an
      unacceptable incidence rate of infection and/or vein thrombosis. This article
      covers our present knowledge regarding catheter indications, technical aspects of
      catheter insertion and care, functional limitation of central venous catheters,
      and catheter-related complications. It is also our intent to provide the reader
      with optimal indication and catheter care in order to prevent and reduce the
      burden of catheter-related morbidity.

PMID- 10910030
TI  - Do automated red cell exchanges relieve priapism in patients with sickle cell
      anemia?
AB  - Priapism is a dramatic, painful complication for some men afflicted by sickle
      cell anemia. Although the natural history remains unclear, many believe replacing
      the patient's abnormal red blood cells (RBCs) with normal RBCs by apheresis is
      effective. However, no controlled trials have demonstrated its effectiveness. We
      exchanged 7 men after medical management failed. All procedures reduced sickle
      hemoglobin levels to < 30%. Two patients underwent emergency automated red cell
      exchanges without any detumescence or reduction of pain. The remaining 5 patients
      were exchanged non-emergently; 4 experienced no detumescence or relief of pain.
      One adult experienced resolution 8 h postexchange. However, he had a history of
      "stuttering" priapism. All required decompression procedures. Automated RBC
      exchanges were not effective in achieving detumescence or reducing pain.

PMID- 10910031
TI  - Frequent beta-catenin gene mutations and accumulations of the protein in the
      putative preneoplastic lesions lacking macroscopic aberrant crypt foci
      appearance, in rat colon carcinogenesis.
AB  - Activating mutations in the beta-catenin gene is thought to be responsible for
      the excessive beta-catenin signaling involved in the majority of carcinogen
      induced colonic carcinomas. To determine whether beta-catenin signaling is
      involved in the initial stage of colon carcinogenesis, mutational analysis of the
      gene and immunohistochemistry for beta-catenin protein were performed in the
      early appearing lesions, including aberrant crypt foci (ACF), of colonic mucosa
      in rats given azoxymethane. Male F344 rats received s.c. injections of
      azoxymethane at a dose of 15 mg/kg body weight, once weekly for 3 weeks, and they
      were sacrificed 10 weeks after the carcinogen treatment. The colonic mucosa was
      examined in en face preparations and in serial sections after the observation in
      whole mount preparations. Microscopical observations in the cross sections have
      shown two populations of histologically altered crypts. The first type had a
      macroscopic feature resembling ACF [histologically altered crypts with ACF
      appearance (HACAs)]. The second type of altered crypts did not have the ACF-like
      appearance and could not be clearly distinguished from adjacent normal crypts in
      whole mount preparations [histologically altered crypts with macroscopically
      normal-like appearance (HACNs)]. The beta-catenin gene mutations were recognized
      in 10 of 15 HACNs (67%) and 3 of 15 HACAs (20%). Frequent immunoreactivity of
      beta-catenin protein was seen in the cytoplasm of HACNs (13 of 15 cases), whereas
      apparent accumulation was not confirmed in any HACAs analyzed. These results
      suggest that (a) there are two types of putative preneoplastic lesions in cancer
      predisposed colonic mucosa, and beta-catenin signaling may contribute to the
      initial stage of colon carcinogenesis; and (b) HACNs are more likely to be direct
      precursors of colon tumors than HACAs in the rat colon carcinogenesis.

PMID- 10910032
TI  - The epidermal growth factor receptor is required to maintain the proliferative
      population in the basal compartment of epidermal tumors.
AB  - Previous studies using keratinocytes from epidermal growth factor receptor (EGFR)
      deficient mice revealed that the EGFR is not required for papilloma formation
      initiated by a mutant rasHa gene, although the tumors that develop are very small
      (A. A. Dlugosz et aL, Cancer Res., 57: 3180-3188, 1997). The current study used a
      combination of bromodeoxyuridine pulse-chase, proliferating cell nuclear antigen
      distribution, and differentiation marker analysis to reveal the following: (a)
      the EGFR was required to maintain the proliferative population in the basal cell
      compartment of papillomas; (b) in the absence of EGFR, cycling tumor cells
      migrated into the suprabasal compartment and initiated the differentiation
      program prematurely; and (c) these changes were associated with cell cycle
      arrest. Further analysis of v-rasHa-transformed EGFR-deficient keratinocytes in
      vitro indicated that such cells migrated more on and attached less to
      extracellular matrix components. Together, these studies reveal that an essential
      function for the EGFR pathway in squamous tumors is to maintain a proliferative
      pool of basal cells and prevent premature terminal differentiation.

PMID- 10910033
TI  - Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis:
      a cancer-prone chronic inflammatory disease.
AB  - Ulcerative colitis (UC) is a chronic inflammatory disease that produces reactive
      oxygen and nitrogen species and increases the risk of colorectal cancer (CRC).
      The p53 tumor suppressor gene is frequently mutated in UC-associated dysplastic
      lesions and CRC. We are exploring the hypothesis that p53 mutations in the
      nontumorous colonic tissue in noncancerous UC cases indicate genetic damage from
      exposure to exogenous and endogenous carcinogens and may identify individuals at
      increased cancer risk. We are reporting, for the first time, the frequency of
      specific p53 mutated alleles in nontumorous colon tissue from donors either with
      or without UC by using a highly sensitive genotypic mutation assay. Higher p53
      mutation frequencies of both G:C to A:T transitions at the CpG site of codon 248
      and C:G to T:A transitions at codon 247 were observed in colon from UC cases when
      compared with normal adult controls (P = 0.001 and P = 0.001, respectively). In
      the UC cases, higher p53 codon 247 and 248 mutation frequencies were observed in
      the inflamed lesional regions when compared with the nonlesional regions of their
      colon (P < 0.001 and P = 0.001). The colonic nitric oxide synthase-2 activity was
      higher in UC cases than in non-UC adult controls (P = 0.02). Our data are
      consistent with the hypothesis that a higher frequency of p53 mutant cells can be
      generated under oxidative stress in people with UC. The increased frequency of
      specific p53 mutated alleles in noncancerous UC colon tissue may confer
      susceptibility to the development of CRC in an inflammatory microenvironment.

PMID- 10910034
TI  - Exisulind induction of apoptosis involves guanosine 3',5'-cyclic monophosphate
      phosphodiesterase inhibition, protein kinase G activation, and attenuated beta
      catenin.
AB  - Sulindac sulfone (exisulind), although a nonsteroidal anti-inflammatory drug
      derivative, induces apoptosis in tumor cells by a mechanism that does not involve
      cyclooxygenase inhibition. SW480 colon tumor cells contain guanosine 3',5'
      monophosphate (cGMP) phosphodiesterase (PDE) isoforms of the PDE5 and PDE2 gene
      families that are inhibited by exisulind and new synthetic analogues. The
      analogues maintain rank order of potency for PDE inhibition, apoptosis induction,
      and growth inhibition. A novel mechanism for exisulind to induce apoptosis is
      studied involving sustained increases in cGMP levels and cGMP-dependent protein
      kinase (PKG) induction not found with selective PDE5 or most other PDE
      inhibitors. Accumulated beta-catenin, shown to be a substrate for PKG, is
      decreased by exisulind, suggesting a mechanism to explain apoptosis induction in
      neoplastic cells harboring adenomatous polyposis coli gene mutations.

PMID- 10910036
TI  - High resolution allelotype of microdissected primary nasopharyngeal carcinoma.
AB  - Nasopharyngeal carcinoma (NPC) is a common cancer in South China but is rare in
      other parts of the world. To better understand the molecular basis of this
      cancer, we performed high-resolution allelotyping on 27 microdissected primary
      tumors using 382 microsatellite markers. We have detected high frequencies of
      allelic imbalance on 3p (96.3%), 9p (85.2%), 9q (88.9%), 11q (74.1%), 12q
      (70.4%), 13q (55.6%), 14q (85.2%), and 16q (55.6%). Nonrandom allelic changes of
      12q and 16q were revealed for the first time. In addition, loss of heterozygosity
      on chromosomal arms 1p (37.0%), 5q (44.4%), and 12p (44.4%) were also common in
      NPC. Multiple minimally deleted regions, 7-40 cM, were identified at 3p14-24.2,
      11q21-23, 13q12-14, 13q31-32, 14q24-32, and 16q22-23. Frequent deletions of these
      minimally deleted regions implied the presence of tumor suppressor genes that may
      be involved in the development of NPC. Consistent loss of heterozygosity on 3p,
      9p, and 14q in almost all tumors suggested that such changes are critical events
      in NPC tumorigenesis.

PMID- 10910035
TI  - Inhibition of metastatic tumor growth in nude mice by portal vein infusions of
      matrix-targeted retroviral vectors bearing a cytocidal cyclin G1 construct.
AB  - Tumor invasion and associated angiogenesis evoke a remodeling of extracellular
      matrix components. Retroviral vectors bearing auxiliary matrix-targeting motifs
      (ie., collagen-binding polypeptides) accumulate at sites of newly exposed
      collagen, thus promoting tumor site-specific gene delivery. In this study, we
      assessed the antitumor effects of serial portal vein infusions of matrix-targeted
      vectors bearing a mutant cyclin G1 (dnG1) construct in a nude mouse model of
      liver metastasis. The size of tumor foci was dramatically reduced in dnG1 vector
      treated mice compared with that in control vector- or PBS-treated animals (P =
      0.0002). These findings represent a definitive advance in the development of
      targeted injectable vectors for metastatic cancer.

PMID- 10910037
TI  - Isolation and characterization of a novel human gene, DRCTNNB1A, the expression
      of which is down-regulated by beta-catenin.
AB  - Beta-catenin plays significant roles in cell-to-cell adhesion and the Wnt/Wg
      signal transduction pathway. Accumulation of this protein in the cytoplasm and
      nucleus as a result of mutations of the adenomatous polyposis coli tumor
      suppressor gene or of the beta-catenin gene itself is often seen in a wide
      variety of tumors including carcinomas of the colon, liver, uterus, and brain.
      Interaction of accumulated beta-catenin with Tcf/Lef transcription factors is
      known to deregulate expression of some downstream genes, but the precise
      mechanisms whereby beta-catenin contributes to carcinogenesis remain to be
      disclosed. Here we report isolation of a novel murine gene, Drctnnb1a (down
      regulated by Ctnnb1, a), the expression of which was experimentally down
      regulated in response to the activated form of beta-catenin. To investigate a
      possible role of DRCTNNB1A in cancers, we also isolated the human homologue,
      DRCTNNB1A, the deduced product of which was 91% identical to the murine protein.
      The transcript was expressed in all human tissues examined, and we assigned the
      genomic location of DRCTNNB1A to chromosomal band 7p15.3 by in situ
      hybridization. Expression of DRCTNNB1A in SW480 colon cancer cells was
      significantly increased in response to reduction of intracellular beta-catenin by
      adenovirus-mediated transfer of the beta-catenin-binding domain of the
      adenomatous polyposis coli gene into the cells. Furthermore, we documented
      reduced expression of DRCTNNB1A in 12 of 15 primary colorectal cancers examined,
      compared with corresponding adjacent noncancerous mucosae. Our results implied
      that DRCTNNB1A is one of the genes involved in the beta-catenin-Tcf/Lef signaling
      pathway, and that reduced expression of DRCTNNB1A may have some role in
      colorectal carcinogenesis.

PMID- 10910038
TI  - Down-regulation of HP1Hsalpha expression is associated with the metastatic
      phenotype in breast cancer.
AB  - We previously identified a down-regulation in heterochromatin-associated protein
      1 (HP1)Hsalpha expression in MDA-MB-231 breast carcinoma cells (highly
      invasive/metastatic) compared with MCF-7 cells (poorly invasive/nonmetastatic).
      In this study, we demonstrate that HP1Hsalpha, but not HP1Hsbeta or HP1Hsgamma,
      is down-regulated at the mRNA and protein levels in highly invasive/metastatic
      breast cancer cell lines. In agreement, little to no nuclear HP1Hsalpha staining
      was observed in these cell lines. In contrast, poorly invasive/nonmetastatic cell
      lines showed HP1Hsalpha localization to the nucleus and nuclear membrane.
      Transfection of MDA-MB-231 cells with a green fluorescent protein-HP1Hsalpha
      expression vector decreased their ability to invade a collagen IV/laminin/gelatin
      matrix compared with green fluorescent protein-transfected controls. Consistent
      with the cell culture studies, immunohistochemical analysis of HP1Hsalpha protein
      localization in distant metastatic tissues from breast cancer patients revealed a
      decrease in the staining intensity and percentage of cells expressing HP1Hsalpha
      in seven of nine distant metastatic lesions compared with normal mammary and
      primary tumors. These results demonstrate a role for HP1Hsalpha in breast cancer
      invasion and metastasis. Given the role of HP1 in transcriptional silencing in
      Drosophila, we propose a model in which HP1Hsalpha normally silences genes
      involved in breast cancer invasion and metastasis.

PMID- 10910039
TI  - Front-cell-specific expression of membrane-type 1 matrix metalloproteinase and
      gelatinase A during cohort migration of colon carcinoma cells induced by
      hepatocyte growth factor/scatter factor.
AB  - Migration of tumor cells is usually assessed as single cell locomotion in vitro
      using Boyden chamber type assays. In vivo, however, carcinoma cells frequently
      invade the surrounding tissue as coherent clusters or nests of cells. We have
      called this type of movement "cohort migration" and developed a two-dimensional
      in vitro cohort migration model, in which human rectal well-differentiated
      adenocarcinoma cells (L-10) migrate from piled-up cell islands as coherent sheets
      of cells when stimulated with hepatocyte growth factor/scatter factor. In this
      study, we examined whether there is a cohort migration-specific way of expression
      of matrix metalloproteinases (MMP) and whether degradation of extracellular
      matrix is necessary for this type of migration. Production of membrane-type 1-MMP
      (MT1-MMP) and gelatinase A (MMP-2) by L-10 cells was demonstrated by gelatin
      zymography, immunoblotting, and reverse transcription-PCR. When cohort migration
      was induced with hepatocyte growth factor/scatter factor, MT1-MMP and MMP-2 were
      immunolocalized predominantly in the leading edges of the front cells of
      migrating cell sheets, with the following cells being negative. In addition,
      during the cohort migration on gelatin-coated substratum, the gelatin matrix was
      degraded by the cells, in a very organized manner, causing radially arrayed lysis
      of gelatin matrix at the sites of leading edges. BB94, a synthetic inhibitor
      specific to MMPs, tissue inhibitor of metalloproteinases-1 and -2, and the COOH
      terminal hemopexin-like domain of MMP-2 inhibited the migration on gelatin
      matrix. Thus, these data demonstrate that gelatin matrix is reorganized to suit
      cell migration via leading-edge-of-front-cell-specific localization of MT1-MMP
      and MMP-2 during cohort migration and suggest that the reorganization is
      essential for this type of migration.

PMID- 10910040
TI  - Frequent alteration of p63 expression in human primary bladder carcinomas.
AB  - p63, a recently identified member of the p53 gene family, encodes multiple
      products with transactivating, death-inducing, and dominant-negative activities.
      To explore the penetrance of p63 in bladder carcinogenesis, we performed
      expression and mutation analyses of two major isotypes, TAp63 and deltaNp63, in
      63 bladder specimens. In 12 normal tissues, TAp63 was expressed at an easily
      detectable level whereas deltaNp63 was absent or extremely low. While none of 47
      carcinomas showed allelic deletion of the gene, marked reduction of TAp63 and
      abnormal overexpression of deltaNp63 were found in 25 (53.2%) and 30 (63.8%)
      carcinomas, respectively. Tumor-specific alteration of TAp63 and deltaNp63
      expression was identified in two and three of six matched sets, respectively. In
      addition, reduced expression of TAp63 showed a correlation with tumor stage and
      grade. Abnormal expression of TAp63 or deltaNp63 isoform was also observed in
      three of four cell lines, and treatment with 5-Aza-2'-deoxycytidine led to up- or
      down-regulation of TAp63 and/or deltaNp63 expression, suggesting that the
      promoters of both isoforms might be affected by DNA methylation, but not in a
      reciprocal fashion. No sequence alteration of p63 was identified in 47 carcinomas
      whereas 17 (34.8%) of these showed p53 mutations, and no association between p63
      expression and the mutational status of p53 or expression of p21Waf1, MDM2, and
      14-3-3sigma was recognized. Our data suggest that altered expression of p63 is a
      frequent event in bladder carcinogenesis and might contribute to the progression
      of bladder tumors, possibly via the mechanism(s) distinct from the p53 pathway.

PMID- 10910041
TI  - Carcinogenic metals induce hypoxia-inducible factor-stimulated transcription by
      reactive oxygen species-independent mechanism.
AB  - Nickel (Ni2+) and cobalt (Co2+) mimic hypoxia and were used as a tool to study
      the role of oxygen sensing and signaling cascades in the regulation of hypoxia
      inducible gene expression. These metals can produce oxidative stress; therefore,
      it was conceivable that reactive oxygen species (ROS) may trigger signaling
      pathways resulting in the activation of the hypoxia-inducible factor (HIF)-1
      transcription factor and up-regulation of hypoxia-related genes. We found that
      the exposure of A549 cells to Co2+ or Ni2+ produced oxidative stress, and
      although Co2+ was a more potent producer of ROS than Ni2+, both metals equally
      increased the expression of Cap43, a hypoxia-regulated gene. The coadministration
      of hydrogen peroxide with metals induced more ROS; however, this did not further
      increase the expression of Cap43 mRNA. The free radical scavenger 2
      mercaptoethanol completely suppressed ROS generation by CoCl2 and NiCl2 but did
      not diminish the induced Cap43 gene expression. The activity of the HIF-1
      transcription factor as assessed in transient transfection assays was stimulated
      by Ni2+, hypoxia, and desferrioxamine, but this activation was not diminished
      when oxidative stress was attenuated nor was HIF-dependent transcription enhanced
      by hydrogen peroxide. We conclude that ROS are produced during the exposure of
      cells to metals that mimic hypoxia, but the formation of ROS was not involved in
      the activation of HIF-1-dependent genes.

PMID- 10910042
TI  - Differential formation of beta-catenin/lymphoid enhancer factor-1 DNA binding
      complex induced by nitric oxide in mouse colonic epithelial cells differing in
      adenomatous polyposis coli (Apc) genotype.
AB  - Increased cytoplasmic beta-catenin levels and the associated nuclear beta
      catenin/T-cell factor (Tcf)-lymphoid enhancer factor (LEF) complex formation have
      been frequently found in colon cancer. In this context, overproduction of nitric
      oxide (NO) attributable to inflammatory stimuli in diseases such as ulcerative
      colitis and Crohn's disease may-contribute to colonic carcinogenesis. Therefore,
      we examined the modulation by NO of cytoplasmic beta-catenin levels and the
      formation of the nuclear beta-catenin/LEF-1 DNA binding complex in conditionally
      immortalized mouse colonic epithelial cells that differed in adenomatous
      polyposis coli (Apc) genotype, namely young adult mouse colon (YAMC; Apc+/+) and
      immortal mouse colon epithelium (IMCE; ApcMin/+). Unlike most colon cancer cell
      lines, this pair of cell lines has either nondetectable or low basal level of
      beta-catenin when they are cultured under nonpermissive and nonproliferative
      conditions. Using electrophoretic mobility shift assays, we found that NO
      releasing agents (E)-methyl-2-[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexeneamide
      and S-nitroso-N-acetylpenicillamine greatly enhanced the formation of beta
      catenin/LEF-1 DNA binding complex in a concentration- and time-dependent fashion
      in YAMC and IMCE cells. Significantly, IMCE cells showed a markedly greater
      amount of nuclear beta-catenin/LEF-1 DNA binding complex in response to NO. Super
      shift by anti-beta-catenin antibody confirmed the presence of beta-catenin in the
      complex. Western blot analysis of the soluble cytoplasmic fractions demonstrated
      that these NO donors caused differential accumulation of cytoplasmic beta-catenin
      in YAMC and IMCE. In conclusion, this study indicates that the defective beta
      catenin degradation machinery attributable to ApcMin/+ mutation in IMCE cells not
      only affects basal levels but also contributes to NO-induced dysregulation of
      cytoplasmic beta-catenin and nuclear beta-catenin/LEF-1 DNA binding complex
      formation.

PMID- 10910043
TI  - Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and
      enhancing ubiquitination of HER-2.
AB  - Overexpression of HER-2/ErbB-2, a homologue of the epidermal growth factor
      receptor, is associated with poor prognosis, and an ErbB-2-specific antibody is
      therapeutic when administered to patients with metastatic breast cancer. To
      understand the mechanism underlying immunotherapy, we concentrated on antibody-
      and epidermal growth factor-induced degradation of ErbB-2. We show that enhanced
      degradation is preceded by poly-ubiquitination of ErbB-2. This process
      necessitates recruitment of the c-Cbl ubiquitin ligase to tyrosine 1112 of ErbB
      2. Consequently, mutagenesis of this site retards antibody-induced degradation.
      Thus, the therapeutic potential of certain antibodies may be due to their ability
      to direct ErbB-2 to a c-Cbl-regulated proteolytic pathway.

PMID- 10910044
TI  - Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and
      human xenograft models.
AB  - Topotecan was encapsulated in sphingomyelin/cholesterol liposomes using an
      ionophore-generated proton gradient. After i.v. injection, liposomal topotecan
      was eliminated from the plasma much more slowly than free drug, resulting in a
      400-fold increase in plasma area under the curve. Further, high-performance
      liquid chromatography analysis of plasma samples demonstrated that topotecan was
      protected from hydrolysis within the liposomal carrier with >80% of the drug
      remaining as the active, lactone species up to 24 h. The improved
      pharmacokinetics observed with liposomal topotecan correlated with increased
      efficacy in both murine and human tumor models. In the L1210 ascitic tumor model,
      optimal doses of liposomal topotecan resulted in a 60-day survival rate of 60
      80%, whereas in a L1210 liver metastasis model, 100% long-term survival (>60
      days) was achieved. In contrast, long-term survivors were rarely seen after
      treatment with free topotecan. Further, in a human breast carcinoma model (MDA
      435/LCC6), liposomal topotecan provided greatly improved increase in life span
      relative to the free drug. These results suggest that liposomal encapsulation can
      significantly enhance the therapeutic activity of topotecan.

PMID- 10910045
TI  - In vivo inhibition of estrone sulfatase activity and growth of nitrosomethylurea
      induced mammary tumors by 667 COUMATE.
AB  - The development of potent steroid sulfatase inhibitors is an important new
      therapeutic strategy for the treatment of postmenopausal women with breast
      cancer. A series of tricyclic coumarin sulfamates were synthesized, and their
      inhibitory properties were examined in vitro and in vivo. In a placental
      microsomal assay system, 667 COUMATE emerged as the most potent inhibitor with an
      IC50 of 8 nM. Administration of a single dose (10 mg/kg, p.o.) of 667 COUMATE
      inhibited rat liver estrone sulfatase activity by 93%. 667 COUMATE was devoid of
      estrogenicity, as indicated by its failure to stimulate the growth of uteri in
      ovariectomized rats. In vivo, estrone sulfate-stimulated growth of uteri in
      ovariectomized rats was inhibited by 667 COUMATE. Using the nitrosomethylurea
      induced mammary tumor model, we found that 667 COUMATE caused regression of
      estrone sulfate-stimulated tumor growth in a dose-dependent manner. The
      identification of 667 COUMATE as a potent steroid sulfatase inhibitor will enable
      the therapeutic potential of this type of therapy to be evaluated.

PMID- 10910046
TI  - Identification of new minimally lost regions on 18q in head and neck squamous
      cell carcinoma.
AB  - Loss of heterozygosity (LOH) on 18q predicts poor survival in head and neck
      squamous cell carcinomas (HNSCCs). Several putative tumor suppressor genes, such
      as DCC, DPC4/Smad4, and MADR2/Smad2, are mapped to 18q, but thus far, the
      important gene locus in HNSCC is not known. To identify possible gene loci on
      18q, we performed LOH studies using tumor DNA from 57 HNSCC primary tumor cell
      lines and DNA isolated from fibroblasts or lymphoblastoid cells from the same
      patients. Forty-two highly polymorphic microsatellite markers spaced not more
      than 5 cM apart (mean distance, 1.82 cM) spanning the region from D18S44 in
      18q11.1 to D18S1141 in 18q23 were used. D18S71 in 18p11.21 on 18p was also used
      to determine whether the short arm was retained. Forty-three of 57 (75%) HNSCC
      lines showed LOH or isolated allelic imbalance (AI) for at least one locus on
      18q. Although many of the cell lines had large distal 18q deletions with a
      breakpoint between 18q11.1 and 18q12.2 to qter, three loci were identified that
      were lost in 70% or more of the cases. The minimally lost regions (MLRs) range in
      size from 1.5-15.79 cM. The most proximal is centered on D18S39 (1.56 cM) in band
      18q21.1, with LOH or isolated AI in 28 of 38 (74%) of informative cases. The
      largest (15.8 cM) begins at D18S61 (28 of 40; 70%) in band 18q22.2 and extends
      through D18S50 in 18q23. The third is centered on D18S70 (30 of 40; 75%) in band
      18q23 (3.67 cM). Of these MLRs, only the one centered on D18S39 has been
      implicated previously in HNSCC. D18S70, the most frequently lost marker, was the
      only marker consistently lost in three tumor cell lines with very minimal losses,
      UM-SCC-19, UM-SCC-67, and UM-SCC-73A. In addition, UM-SCC-91 exhibited AI only at
      this locus, and UT-SCC-4 had AI at D18S70 and D18S39 only. Close physical mapping
      of these three regions may pinpoint one or more previously unidentified tumor
      suppressor genes.

PMID- 10910047
TI  - Biallelic methylation and silencing of mouse Aprt in normal kidney cells.
AB  - Heritable gene silencing is an important mechanism of tumor suppressor gene
      inactivation in a variety of human cancers. In the present study, we show that
      methylation-associated silencing of the autosomal adenine
      phosphoribosyltransferase (Aprt) locus occurs in primary mouse kidney cells. Aprt
      deficient cells were isolated from mice that were heterozygous for Aprt, i.e.,
      they contained one wild-type Aprt allele and one targeted allele bearing an
      insertion of the bacterial neo gene. Although silencing of the wild-type allele
      alone was sufficient for the cells to become completely Aprt-deficient, biallelic
      methylation of the promoter region was found to occur. Moreover, despite the
      absence of selective pressure against the targeted allele, phenotypic silencing
      of the inserted neo gene accompanied silencing of the wild-type Aprt allele. A
      potential role for allelic homology in these events is discussed.

PMID- 10910048
TI  - BCR-ABL mediates arsenic trioxide-induced apoptosis independently of its aberrant
      kinase activity.
AB  - In the prechemotherapy era arsenic derivatives were used for treatment of chronic
      myelogenous leukemia, a myeloproliferative disorder characterized by the t(9;22)
      translocation, the Philadelphia chromosome (Ph+). In acute promyelocytic leukemia
      response to arsenic trioxide (As2O3) has been shown to be genetically determined
      by the acute promyelocytic leukemia-specific t(15;17) translocation product
      PML/RARalpha. Hence, we reasoned that As2O3 might have a selective inhibitory
      effect on proliferation of BCR-ABL-expressing cells. Here, we report that: (a)
      As2O3 induced apoptosis in Ph+ but not in Ph- lymphoblasts; (b) enforced
      expression of BCR-ABL in U937 cells dramatically increased the sensitivity to
      As2O3; (c) the effect of As2O3 was independent of BCR-ABL kinase activity; and
      (d) As2O3 reduced proliferation of chronic myelogenous leukemia blasts but not of
      peripheral CD34+ progenitors. In summary, these data establish As2O3 as a tumor
      cell-specific agent, making its clinical application in Ph+ leukemia feasible.

PMID- 10910049
TI  - Reproductive state of rat mammary gland stroma modulates human breast cancer cell
      migration and invasion.
AB  - It has been established that the invasive behavior of cancer cells can be
      regulated by alterations in their extracellular environment. We investigated
      whether extracellular matrix isolated from nulliparous and postlactating
      (involuting) rat mammary glands differentially modulated the metastatic behavior
      of human breast cancer cells. Using modified Boyden chamber and three-dimensional
      culture assays, nulliparous mammary matrix was found to suppress motility and
      invasion in highly metastatic MDA-MB-435 cells, whereas involution mammary matrix
      supported motility and invasion in highly metastatic MDA-MB-435 cells, but not in
      cells with low metastatic potential. Biochemical characterization of the matrices
      revealed intact fibronectin (FN) and low matrix metalloproteinase activity in
      nulliparous mammary matrix and fragmented FN and high matrix metalloproteinase
      activity in the matrix isolated from involuting glands. Purified intact FN was
      found to inhibit cell invasiveness, whereas FN fragments enhanced cell
      invasiveness in a matrix metalloproteinase-dependent manner. These data suggest
      that physiological changes that occur in the mammary extracellular matrix as a
      result of reproductive status alter the in vitro parameters of metastatic
      potential.

PMID- 10910050
TI  - Human carcinoembryonic antigen functions as a general inhibitor of anoikis.
AB  - Human carcinoembryonic antigen (CEA), a widely used tumor marker, and CEACAM6
      [formerly nonspecific cross-reacting antigen (NCA)] are up-regulated in many
      types of human cancers, whereas family member CEACAM1 [formerly biliary
      glycoprotein (BGP)] is usually down-regulated. Deregulated overexpression of
      CEA/CEACAM6 but not CEACAM1 can inhibit the differentiation and disrupt the
      polarization and tissue architecture of many different types of cells. In this
      report, we show that CEA and CEACAM6, but not CEACAM1, markedly inhibit the
      apoptosis of cells when deprived of their anchorage to the extracellular matrix,
      a process known as anoikis. By blocking this tissue architecture surveillance
      mechanism, the architectural perturbation initiated by CEA/CEACAM6 can thus be
      maintained.

PMID- 10910051
TI  - Loss of cell cycle control allows selective microtubule-active drug-induced Bcl-2
      phosphorylation and cytotoxicity in autonomous cancer cells.
AB  - Lack of selectivity in the killing of tumor and normal cells is a major obstacle
      in cancer therapy. By inhibiting normal but not autonomous cell growth, we
      exploited the differences in cell cycle regulation to achieve a selective
      protection of nonautonomous cells against paclitaxel and other microtubule-active
      drugs. Tubulin polymerization, a primary effect of paclitaxel, can be dissociated
      from Bcl-2 phosphorylation and cytotoxicity in HL-60 cells. Growth arrest
      prevented paclitaxel-induced Bcl-2 phosphorylation and apoptosis without
      affecting paclitaxel-induced tubulin polymerization. We abrogated the effects of
      paclitaxel on MCF-10A immortalized breast cells, while preserving its effects on
      MCF-7 cancer cells. Unlike MCF-7 cells, MCF-10A cells were arrested by epidermal
      growth factor withdrawal, precluding paclitaxel-induced Bcl-2 phosphorylation.
      Furthermore, the inhibition of the epidermal growth factor receptor kinase with
      low doses of AG1478 arrested growth of MCF-10A but not MCF-7 cells. Pretreatment
      with AG1478 did not affect paclitaxel-induced Bcl-2/Raf-1 phosphorylation in MCF
      7 but abrogated such phosphorylation in MCF-10A. Exploitation of growth factor
      dependency may allow the protection of normal cells from microtubule-active
      drugs.

PMID- 10910052
TI  - Differential expression of cell surface molecules in prostate cancer cells.
AB  - The expression of 119 cell surface molecules was catalogued for three prostate
      cancer cell lines, LNCaP, PC3, and DU145, all of which were established from
      metastases. Many of these molecules are common to all three cell lines, whereas
      some are differentially expressed. More prostate basal epithelial cell-specific
      than luminal epithelial cell-specific molecules are detected, especially in DU145
      and PC3 cells. The cancer cells also express molecules that are not normally
      associated with prostate epithelial cells. As a population, expression of these
      molecules appears to be heterogeneous. This heterogeneity may be an inherent
      property of the population.

PMID- 10910053
TI  - Heat-induced gene expression as a novel targeted cancer gene therapy strategy.
AB  - One of the main advantages of gene therapy over traditional therapy is the
      potential to target the expression of therapeutic genes in desired cells or
      tissues. To achieve targeted gene expression, we experimented with a new approach
      based on the long-established phenomenon of the heat shock response. By using the
      green fluorescence protein as a reporter gene, it was demonstrated that
      expression of a heterologous gene with a heat shock protein 70 promoter could be
      elevated to 500-1000-fold over background by moderate hyperthermia (39 degrees C
      to 43 degrees C) in tissue cultured cells. The heat-induced green fluorescence
      protein expression was first detectable at 3 h after heating and reached a
      maximum at 18-24 h. The expression dropped back to baseline within 72 h. In
      addition, when cells were infected with adenovirus vectors containing the heat
      inducible interleukin 12 or tumor necrosis factor alpha genes and then heated (42
      degrees C, 30 min), expression was at least 13,600- or 6.8 x 10(5)-fold over
      background, respectively. Intralesion injection of the interleukin-12-carrying
      adenovirus vector in a mouse melanoma tumor model caused significant tumor growth
      delay only with hyperthermia treatment. Our results therefore support heat
      induced gene expression as a feasible approach for targeted cancer gene therapy.

PMID- 10910054
TI  - Cytochrome P450 1B1 (CYP1B1) pharmacogenetics: association of polymorphisms with
      functional differences in estrogen hydroxylation activity.
AB  - Activation of 17beta-estradiol (E2) through the formation of catechol estrogen
      metabolites, 2-OH-E2 and 4-OH-E2, and the C-16alpha hydroxylation product,
      16alpha-OH-E2, has been postulated to be a factor in mammary carcinogenesis.
      Cytochrome P450 1B1 (CYP1B1) exceeds other P450 enzymes in both estrogen
      hydroxylation activity and expression level in breast tissue. To determine
      whether inherited variants of CYP1B1 differ from wild-type CYP1B1 in estrogen
      hydroxylase activity, we expressed recombinant wild-type and five polymorphic
      variants of CYP1B1: variant 1 (codon 48Arg-->Gly), variant 2 (codon 119Ala-
      >Ser), variant 3 (codon 432Val-->Leu), variant 4 (codon453Asn-->Ser), variant 5
      (48Gly, 119Ser, 432Leu, 453Ser). The His-tagged proteins were purified by nickel
      nitrilotriacetic acid (Ni-NTA) chromatography and analyzed by electrophoresis and
      spectrophotometry. We performed assays of E2 hydroxylation activity and
      quantitated production of 2-OH-E2, 4-OH-E2, and 16alpha-OH-E2 by gas
      chromatography/mass spectrometry. Wild-type CYP1B1 formed 4-OH-E2 as main product
      (Km, 40+/-8 microM; k(cat) 4.4+/-0.4, min(-1); k(cat)/Km, 110 mM(-1) min(-1)),
      followed by 2-OH-E2 (Km, 34+/-4 microM; k(cat), 1.9+/-0.1 min(-1); k(cat)/Km, 55
      mM(-1)min(-1)) and 16alpha-OH-E2 (Km, 39+/-5.7 microM; k(cat), 0.30+/-0.02 min(
      1); k(cat)/Km, 7.6 mM(-1)min(-1)). The CYP1B1 variants also formed 4-OH-E2 as the
      main product but displayed 2.4- to 3.4-fold higher catalytic efficiencies
      k(cat)/Km than the wild-type enzyme, ranging from 270 mM(-1)min(-1) for variant
      4, to 370 mM(-1)min(-1) for variant 2. The variant enzymes also exceeded wild
      type CYP1B1 with respect to 2- and 16alpha-hydroxylation activity. Thus,
      inherited alterations in CYP1B1 estrogen hydroxylation activity may be associated
      with significant changes in estrogen metabolism and, thereby, may possibly
      explain interindividual differences in breast cancer risk associated with
      estrogen-mediated carcinogenicity.

PMID- 10910055
TI  - Arsenic mediates cell proliferation and gene expression in the bladder
      epithelium: association with activating protein-1 transactivation.
AB  - Although the mechanism of action has not yet been defined, epidemiological
      studies have demonstrated an association between elevated arsenic levels in
      drinking water and the incidence of urinary bladder transitional cell carcinomas.
      In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite
      in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of
      exposure. This was accompanied by the accumulation of inorganic trivalent
      arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well
      as a persistent increase in DNA binding of the activating protein (AP)-1
      transcription factor. AP-1 transactivation by arsenic also occurred in bladders
      of transgenic mice containing an AP-1 luciferase reporter. Consistent with these
      in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding
      in a human bladder epithelial cell line. Gene expression studies using RNase
      protection assays, reverse transcription-PCR, and cDNA microarrays indicated that
      arsenite alters the expression of a number of genes associated with cell growth,
      such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and
      GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells
      likely contributes to its ability to cause cancer.

PMID- 10910056
TI  - Cytochrome P4501B1 mediates induction of bone marrow cytotoxicity and preleukemia
      cells in mice treated with 7,12-dimethylbenz[a]anthracene.
AB  - Humans are exposed to polycyclic aromatic hydrocarbons (PAHs) through many
      environmental pollutants, especially cigarette smoke. These chemicals cause a
      variety of tumors and immunotoxic effects, as a consequence of bioactivation by P
      450 cytochromes to dihydrodiol epoxides. The recently identified cytochrome
      P4501B1 (CYP1B1) bioactivates PAHs but is also a physiological regulator, as
      evidenced by linkage of CYP1B1 deficiency to congenital human glaucoma. This
      investigation demonstrates that CYP1B1 null mice are almost completely protected
      from the acute bone marrow cytotoxic and preleukemic effects of the prototypic
      PAH 7,12-dimethylbenz[a]anthracene (DMBA). CYP1B1 null mice did not produce the
      appreciable amounts of bone marrow DMBA dihydrodiol epoxide DNA adducts present
      in wild-type mice, despite comparable hepatic inductions of the prominent PAH
      metabolizing P-450 cytochrome, CYP1A1. Wild-type mice constitutively expressed
      low levels of bone marrow CYP1B1. These findings suggest that CYP1B1 is
      responsible for the formation of DMBA dihydrodiol epoxides in the bone marrow.
      Furthermore, this study substantiates the importance of DMBA dihydrodiol epoxide
      generation at the site of cancer initiation and suggests that tissue-specific
      constitutive CYP1B1 expression may contribute to cancer susceptibility in the
      human population.

PMID- 10910057
TI  - Mice heterozygous for a Brca1 or Brca2 mutation display distinct mammary gland
      and ovarian phenotypes in response to diethylstilbestrol.
AB  - Women who inherit mutations in the breast cancer susceptibility genes, BRCA1 and
      BRCA2, are predisposed to the development of breast and ovarian cancer. We used
      mice with a Brca1 mutation on a BALB/cJ inbred background (BALB/cB1+/- mice) or a
      Brca2 genetic alteration on the 129/SvEv genetic background (129B2+/- mice) to
      investigate potential gene-environment interactions between defects in these
      genes and treatment with the highly estrogenic compound diethylstilbestrol (DES).
      Beginning at 3 weeks of age, BALB/cB1+/-, 129B2+/-, and wild-type female mice
      were fed a control diet or a diet containing 640 ppb DES for 26 weeks. DES
      treatment caused vaginal epithelial hyperplasia and hyperkeratosis, uterine
      inflammation, adenomyosis, and fibrosis, as well as oviductal smooth muscle
      hypertrophy. The severity of the DES response was mouse strain specific. The
      estrogen-responsive 129/SvEv strain exhibited an extreme response in the
      reproductive tract, whereas the effect in BALB/cJ and C3H/HeN(MMTV-) mice was
      less severe. The Brca1 and Brca2 genetic alterations influenced the phenotypic
      response of BALB/cJ and 129/SvEv inbred strains, respectively, to DES in the
      mammary gland and ovary. The mammary duct branching morphology was inhibited in
      DES-treated BALB/cB1+/- mice compared with similarly treated BALB/cB1+/+
      littermates. In addition, the majority of BALB/cB1+/- mice had atrophied ovaries,
      whereas wild-type littermates were largely diagnosed with arrested follicular
      development. The mammary ductal architecture in untreated 129B2+/- mice revealed
      a subtle inhibited branching phenotype that was enhanced with DES treatment.
      However, no significant differences were observed in ovarian pathology between
      129B2+/+ and 129B2+/- mice. These data suggest that estrogenic compounds may
      modulate mammary gland or ovarian morphology in BALB/cB1+/- and 129B2+/- mice.
      These observations are consistent with the hypothesis that compromised DNA repair
      processes in cells harboring Brca1 or Brca2 mutations lead to inhibited growth
      and differentiation compared with the proliferative response of wild-type cells
      to DES treatment.

PMID- 10910058
TI  - A plasmin-derived hexapeptide from the carboxyl end of osteocalcin counteracts
      oxytocin-mediated growth inhibition [corrected] of osteosarcoma cells.
AB  - We have previously described the presence of the functional plasminogen activator
      system on the surfaces of bone neoplastic cells and the fact that plasmin
      specifically cleaves bone matrix protein osteocalcin (OC). The cleavage of OC to
      NH2-midterminal (1-44) and COOH-terminal RFYGPV hexapeptide (44-49) proceeds with
      detachment of both products from bone mineral. Because the sequence of OC-derived
      hexapeptide (HP) is nearly identical to the E2 region of the oxytocin receptor
      (OTR), we set out to ascertain whether the HP interferes with the osteosarcoma
      (OS)-associated oxytocin (OT) system. We documented the presence and functional
      activity of OTRs in several OS cells by means of (a) OT-mediated inhibition of OS
      growth; (b) expression of OTR mRNA by means of reverse transcription-PCR; (c)
      immunofluorescence staining with IF3 monoclonal antibody specific for human OTR;
      and (d) saturation binding and Scatchard analysis of OT binding to the receptors
      of isolated membranes or intact OS cells. Although we could not demonstrate
      direct binding of HP to OT, the presence of HP in cultures of OS cells
      antagonizes the inhibitory effect of OT on these cells. Additionally, in
      competitive binding assays, the HP effectively competes with binding of OT to its
      cognate receptors. The results indicate the existence of an OTR/OT system in
      tumor cells of bone origin. Suggested plasminogen activator-OC-OTR/OT
      interactions may have an effect on the regulation of cell proliferation within
      the bone tissue as well as properties of the extracellular matrix surrounding the
      tumor foci in the bone.

PMID- 10910059
TI  - Chemopreventive properties of trans-resveratrol are associated with inhibition of
      activation of the IkappaB kinase.
AB  - trans-Resveratrol (Res), a phytoalexin found at high levels in grapes and in
      grape products such as red wine, has been shown to have anti-inflammatory and
      antioncogenic properties. Because the transcription factor nuclear factor kappaB
      (NF-kappaB) is involved in inflammatory diseases and oncogenesis, we tested
      whether Res could modulate NF-kappaB activity. Res was shown to be a potent
      inhibitor of both NF-kappaB activation and NF-kappaB-dependent gene expression
      through its ability to inhibit IkappaB kinase activity, the key regulator in NF
      kappaB activation, likely by inhibiting an upstream signaling component. In
      addition, Res blocked the expression of mRNA-encoding monocyte chemoattractant
      protein-1, a NF-kappaB-regulated gene. Relative to cancer chemopreventive
      properties, Res induced apoptosis in fibroblasts after the induced expression of
      oncogenic H-Ras. Thus, Res is likely to function by inhibiting inflammatory and
      oncogenic diseases, at least in part, through the inhibition of NF-kappaB
      activation by blocking IkappaB kinase activity. These data may also explain
      aspects of the so-called "French paradox" that is associated with reduced
      mortality from coronary heart disease and certain cancers and provide a molecular
      rationale for the role of a potent chemopreventive compound in blocking the
      initiation of inflammation and oncogenesis.

PMID- 10910060
TI  - Adenovirus-mediated transfer of the thyroid sodium/iodide symporter gene into
      tumors for a targeted radiotherapy.
AB  - The Na+/I- symporter (NIS) present in the membranes of thyroid cells is
      responsible for the capacity of the thyroid to concentrate iodide. This allows
      treatment of thyroid cancers with 131I. We propose to enlarge this therapeutic
      strategy to nonthyroid tumors by using an adenoviral vector to deliver the NIS
      gene into the tumor cells. We constructed a recombinant adenovirus encoding the
      rat NIS gene under the control of the cytomegalovirus promoter (AdNIS). Infection
      of SiHa cells (human cervix tumor cells) with AdNIS resulted in perchlorate
      sensitive 125I uptake by these cells to a level 125-225 times higher than that in
      noninfected cells. Similar results were obtained for other human tumor cell
      lines, including MCF7 and T-47D (mammary gland), DU 145 and PC-3 (prostate), A549
      (lung), and HT-29 (colon), demonstrating that the AdNIS vector can function in
      tumor cells of various origins. In addition, AdNIS-infected tumor cells were
      selectively killed by exposure to 131I, as revealed by clonogenic assays. To
      assess the efficiency of this cancer gene therapy strategy in vivo, we injected
      the AdNIS vector in human tumors (SiHa or MCF7 cells) established s.c. in nude
      mice. Immunohistological analysis confirmed the expression of the NIS protein in
      the tumor. Three days after intratumoral injection, AdNIS-treated tumors could
      specifically accumulate 125I or 123I, as revealed by kinetics and imaging
      experiments. A quantitative analysis demonstrated that the uptake in AdNIS
      injected tumors was 4-25 times higher than that in nontreated tumors. On average,
      11% of the total amount of injected 125I could be recovered per gram of AdNIS
      treated tumor tissue. Altogether, these data indicate that AdNIS is very
      efficient in triggering significant iodide uptake by a tumor, outlining the
      potential of this novel cancer gene therapy approach for a targeted radiotherapy.

PMID- 10910061
TI  - dUTP nucleotidohydrolase isoform expression in normal and neoplastic tissues:
      association with survival and response to 5-fluorouracil in colorectal cancer.
AB  - Aberrant dUTP metabolism plays a significant role in the underlying molecular
      mechanisms of cell killing mediated by inhibitors of thymidylate biosynthesis.
      dUTP nucleotidohydrolase (dUTPase) is the key regulator of dUTP pools, and
      significant evidence exists suggesting that the expression of this enzyme may be
      an important determinant of cytotoxicity mediated by inhibitors of thymidylate
      synthase (TS). In this study, we have determined the expression patterns of
      dUTPase in normal and neoplastic tissues and examined the association between
      dUTPase expression and response to 5-fluorouracil (5-FU)-based chemotherapy and
      overall survival in colorectal cancer. Immunohistochemistry was performed on
      formalin-fixed, paraffin-embedded tissue sections using a monoclonal antibody
      (MAb), DUT415, that cross-reacts with both nuclear and mitochondrial isoforms of
      human dUTPase. Nuclear and cytoplasmic staining was observed in both normal and
      neoplastic tissues. In normal tissues, nuclear dUTPase staining was observed
      exclusively in replicating cell types. This observation is in agreement with cell
      culture studies where expression of the nuclear isoform (DUT-N) is proliferation
      dependent In contrast, cytoplasmic expression of dUTPase does not correlate with
      proliferation status and was observed in tissues rich in mitochondria. Consistent
      with this observation, cell culture studies reveal that the mitochondrial isoform
      (DUT-M) is expressed constitutively, independent of cell cycle status. These data
      suggest that in normal tissues, nuclear staining with the DUT415 antibody
      represents the DUT-N isoform, whereas cytoplasmic staining represents the DUT-M
      isoform. In colon cancer tumor specimens, expression of dUTPase was shown to be
      highly variable in both amount and intracellular localization. Patterns of
      dUTPase protein expression observed included exclusive nuclear, exclusive
      cytoplasmic, and combined nuclear and cytoplasmic staining. Thus,
      immunohistochemical detection of dUTPase in colon cancers provides distinct
      intracellular phenotypes of expression that may be of significant prognostic
      value. To examine the association between dUTPase expression and response to 5-FU
      based chemotherapy and overall survival, we initiated a retrospective study
      including tumor specimens from 20 patients who had received protracted infusion
      of 5-FU and leucovorin for treatment of metastatic colon cancer. Positive nuclear
      staining was found in 8 patients, whereas 12 lacked nuclear expression. Of the
      patients lacking nuclear dUTPase expression, 6 responded to 5-FU-based
      chemotherapy, 4 had stable disease, and 2 had progressive disease. Of the
      patients presenting positive nuclear dUTPase expression, 0 responded to
      chemotherapy, 1 had stable disease, and 7 had progressive disease (P = 0.005).
      The median survival for patients with tumors lacking nuclear staining was 8.5
      months and 6.9 months for patients with tumors demonstrating positive nuclear
      dUTPase expression (P = 0.09). Time to progression was significantly longer for
      patients with tumors lacking nuclear staining (P = 0.017). Variable cytoplasmic
      dUTPase expression was observed in these tumors; however, there was no apparent
      association with clinical response or survival in this limited study. Nuclear
      dUTPase staining within these tumors was also associated with TS gene expression
      (P = 0.06). This study demonstrates that low intratumoral levels of nuclear
      dUTPase protein expression is associated with response to 5-FU-based
      chemotherapy, greater time to progression, and greater overall survival in
      colorectal cancer. Conversely, high levels of nuclear dUTPase protein expression
      predict for tumor resistance to chemotherapy, shorter time to progression, and
      shorter overall survival. This report represents the first clinical study
      implicating dUTPase overexpression as a mechanism of resistance to TS inhibitor
      based chemotherapy.

PMID- 10910062
TI  - A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and
      the mammalian target of rapamycin in mitogen-stimulated and transformed cells.
AB  - The microbially derived antiproliferative agent rapamycin inhibits cell growth by
      interfering with the signaling functions of the mammalian target of rapamycin
      (mTOR). In this study, we demonstrate that interleukin-3 stimulation induces a
      wortmannin-sensitive increase in mTOR kinase activity in a myeloid progenitor
      cell line. The involvement of phosphoinositide 3'-kinase (PI3K) in the regulation
      of mTOR activity was further suggested by findings that mTOR was phosphorylated
      in vitro and in vivo by the PI3K-regulated protein kinase, AKT/PKB. Although AKT
      phosphorylated mTOR at two COOH-terminal sites (Thr2446 and Ser2448) in vitro,
      Ser2448 was the major phosphorylation site in insulin-stimulated or -activated
      AKT-expressing human embryonic kidney cells. Transient transfection assays with
      mTOR mutants bearing Ala substitutions at Ser2448 and/or Thr2446 indicated that
      AKT-dependent mTOR phosphorylation was not essential for either PHAS-I
      phosphorylation or p70S6K activation in HEK cells. However, a deletion of amino
      acids 2430-2450 in mTOR, which includes the potential AKT phosphorylation sites,
      significantly increased both the basal protein kinase activity and in vivo
      signaling functions of mTOR. These results demonstrate that mTOR is a direct
      target of the PI3K-AKT signaling pathway in mitogen-stimulated cells, and that
      the identified AKT phosphorylation sites are nested within a "repressor domain"
      that negatively regulates the catalytic activity of mTOR. Furthermore, the
      activation status of the PI3K-AKT pathway in cancer cells may be an important
      determinant of cellular sensitivity to the cytostatic effect of rapamycin.

PMID- 10910063
TI  - Methotrexate cross-resistance in a mitoxantrone-selected multidrug-resistant MCF7
      breast cancer cell line is attributable to enhanced energy-dependent drug efflux.
AB  - Cellular resistance to the antifolate methotrexate (MTX) is often caused by
      target amplification, uptake defects, or alterations in polyglutamylation. Here
      we have examined MTX cross-resistance in a human breast carcinoma cell line
      (MCF7/MX) selected in the presence of mitoxantrone, an anticancer agent
      associated with the multidrug resistance (MDR) phenotype. Examination of protein
      expression and enzyme activities showed that MCF7/MX cells displayed none of the
      classical mechanisms of MTX resistance. They did, however, exhibit an ATP
      sensitive accumulation defect accompanied by reduced polyglutamylation. Although
      the kinetics of drug uptake was similar between parental and resistant cells, the
      resistant cells exhibited increased energy-dependent drug efflux. This suggested
      the involvement of an ATP-binding cassette (ABC) transporter. However, cells
      transfected with the breast cancer resistance protein (BCRP)-the ABC transporter
      known to be highly overexpressed in MCF7/MX cells and to confer mitoxantrone
      resistance (D. D. Ross et al., J. Natl. Cancer Inst. 91: 429-433, 1999)-were not
      MTX resistant, which suggested that this transporter is not involved in MTX cross
      resistance. Moreover, members of the MRP protein family of transport proteins,
      which had previously been implicated in MTX resistance, were not found to be
      overexpressed in the MCF7/MX cells. Thus, our data suggest that a novel MTX
      specific efflux pump may be involved in this unusual cross-resistance phenotype.

PMID- 10910064
TI  - Differential signaling by an anti-p185(HER2) antibody and heregulin.
AB  - To understand the molecular mechanisms by which anti-p185HER2 antibody and the
      ligand heregulin inhibit tumor growth, we have investigated several signaling
      proteins and pathways. We report here that anti-p185HER2 monoclonal antibody ID5
      induced tyrosine phosphorylation of HER2 in SKBr3 breast cancer cells that
      overexpress p185HER2. Heregulin beta1 induced phosphorylation of both HER3 and
      HER2. ID5 produced a greater association of phospholipase C (PLC)-gamma1 with
      HER2 than did heregulin. Concordantly, ID5, but not heregulin, increased PLC
      gamma1 activity. However, the G1 cell cycle arrest and induction of p27Kip1
      produced by ID5 were not affected by the inhibition of PLC-gamma. ID5
      preferentially induced binding of the Mr 46,000 isoform of SHC to HER2, whereas
      heregulin preferentially induced binding of the Mr 52,00 isoform of SHC to HER3.
      Heregulin, but not ID5, induced the p85 subunit of phosphatidylinositol 3'-kinase
      (PI3-K) to interact with HER3. Heregulin induced sustained activation of P13-K
      signaling, whereas ID5 had only a transient effect. Heregulin, but not ID5,
      activated the c-Jun-NH2-terminal kinase cascade. Pretreatment of SKBr3 cells with
      ID5 decreased heregulin-induced association of HER2 with HER3 as well as the
      activation of c-Jun-NH2-terminal kinase and PI3-K activities. Inhibition of the
      mitogen-activated protein kinase pathway in SKBr3 cells did not affect heregulin
      induced G2-M-phase arrest, apoptosis, and differentiation. Heregulin-induced
      apoptosis could be blocked by inhibition of p70s6k, but not by inhibition of PI3
      K. Heregulin-induced differentiation could be eliminated by inhibition of PI3-K.
      We conclude that ID5 and heregulin signal via different pathways, although both
      agents can inhibit the clonogenic growth of cells that overexpress HER2.

PMID- 10910065
TI  - Intracellular acidification of human melanoma xenografts by the respiratory
      inhibitor m-iodobenzylguanidine plus hyperglycemia: a 31P magnetic resonance
      spectroscopy study.
AB  - In vivo 31P magnetic resonance spectroscopy demonstrates that human melanoma
      xenografts can be significantly acidified by induction of hyperglycemia combined
      with administration of m-iodobenzylguanidine (MIBG), an inhibitor of
      mitochondrial respiration. In melanoma xenografts (< or =8 mm diameter),
      intracellular pH (pHi, measured by the chemical shift of the Pi resonance) and
      extracellular pH (pHe, measured with 3-aminopropylphosphonate) was reduced by
      less than 0.2 unit during i.v. infusion of glucose for 40 min. Administration of
      MIBG (30 mg/kg) under hyperglycemic conditions (26 mM) reduced tumor pHi and pHe
      by approximately 0.4 (P < 0.001) and approximately 0.6 (P < 0.001) unit,
      respectively; coincidentally, the nucleoside triphosphates:Pi ratio decreased
      approximately 60% (P < 0.004) relative to the baseline level. Minimal changes in
      pHi and pHe and a small decrease in nucleoside triphosphates:Pi ratio (26%, P =
      0.2) were observed in liver in response to MIBG plus hyperglycemia. These results
      suggest that under normoglycemic and hyperglycemic conditions, small human
      melanoma xenografts (< or =8 mm) may exhibit a relatively high level of oxidative
      phosphorylation that may be blocked by MIBG. The acidification may result from
      increased lactate production as a direct effect of MIBG inhibition of respiration
      in mitochondria of tumor cells, or through indirect systemic effects, which
      remain to be identified. The synergetic effects of MIBG and hyperglycemia result
      in significant acidification of the tumor and a decrease in tumor bioenergetic
      status, and the effects are largely selective for tumors in comparison with
      normal tissues.

PMID- 10910066
TI  - Taxol and anti-stathmin therapy: a synergistic combination that targets the
      mitotic spindle.
AB  - Stathmin is an abundant cytosolic phosphoprotein that plays an important role in
      the regulation of cellular proliferation. Its major function is to promote
      depolymerization of the microtubules that make up the mitotic spindle. Taxol is
      an effective chemotherapeutic agent whose activity is mediated through
      stabilization of the microtubules of the mitotic spindle. We demonstrate that
      antisense inhibition of stathmin expression chemosensitizes K562 leukemic cells
      to the antitumor effects of Taxol and results in a synergistic inhibition of
      their growth and clonogenic potential. In the presence of stathmin inhibition,
      exposure to Taxol results in more severe mitotic abnormalities (hypodiploidy and
      multinucleation). This, in turn, results in increased apoptosis of the aneuploid
      cells during subsequent cell division cycles. This novel molecular-based
      therapeutic approach may provide an effective form of cancer therapy that would
      avoid the severe toxicities associated with the use of multiple chemotherapeutic
      agents with overlapping toxicity profiles.

PMID- 10910067
TI  - Generation of tumor-specific T-lymphocytes by cross-priming with human dendritic
      cells ingesting apoptotic tumor cells.
AB  - It has been suggested that dendritic cells (DCs) are capable of ingesting
      apoptotic tumor cells (ATCs) and presenting tumor-associated antigens to immune
      cells. We evaluated the potential of human DCs, which have ingested ATCs, to
      serve as a source of antigenic epitopes for presentation to T cells specific for
      PCI-13, a squamous cell carcinoma of the head and neck cell line. Immature DCs
      (DCimm) generated in the presence of interleukin 4 and granulocyte machrophage
      colony-stimulating factor from peripheral blood monocytes of HLA-A2+ healthy
      donors were incubated in the presence of ATCs. Uptake of ATCs by DCs was
      monitored by flow cytometry and confocal microscopy after 2-18 h of coincubation.
      When DCs were matured (DCmat) in the presence of proinflammatory cytokines, their
      capacity to uptake ATCs was reduced. Responses of PCI-13-specific CD8+ T cells to
      unmodified PCI-13 cells and to DCimm or DCmat +/- ATCs or +/- tumor lysates were
      tested in gamma-IFN enzyme-linked immunospot and cytotoxicity assays. Unmodified
      tumor cells were found to be the best stimulators of antitumor activity of the
      established T-cell line, and ATCs alone were minimally stimulatory. However, DCs
      that ingested ATCs were able to present tumor antigens to CTLs, and DCimm and
      DCmat were almost equally stimulatory. When DCs plus various tumor-derived
      preparations were used as antigen-presenting cells with autologous HLA-A2+ T
      cells obtained from normal donors, DCs that had ingested ATCs were more effective
      in generating CD8+ CTLs than tumor cells alone or DCs pulsed with tumor lysates.
      The results indicate that human DCs fed with ATCs and then matured effectively
      generated T cell-mediated antitumor responses in vitro.

PMID- 10910068
TI  - Identification of a new endoplasmic reticulum-resident protein recognized by HLA
      A24-restricted tumor-infiltrating lymphocytes of lung cancer.
AB  - To help clarify the molecular basis of tumor immunology in lung cancer, we have
      investigated antigens recognized by HLA-A24-restricted CTLs established from T
      cells infiltrating into lung adenocarcinoma and report a new gene encoding tumor
      epitopes recognized by the CTLs. This gene was located on chromosome 4q31.22 and
      encoded an unreported endoplasmic reticulum-resident protein with 412 deduced
      amino acids. This protein had a molecular mass of 46 kDa and was expressed in the
      majority of malignant cells and tissues tested, with the exception of T-cell
      leukemia cells, but was not expressed in a panel of normal cells and tissues,
      except in those of the testis, placenta, and fetal liver. Two peptides at
      positions 13-20 and 75-84 were recognized by the CTLs and had an ability to
      induce HLA-A24-restricted and tumor-specific CTLs in peripheral blood mononuclear
      cells of lung cancer patients. Thus, these peptides might be appropriate
      molecules for use in the specific immunotherapy of HLA-A24+ patients with lung
      and other cancers.

PMID- 10910069
TI  - Peripheral burst of tumor-specific cytotoxic T lymphocytes and infiltration of
      metastatic lesions by memory CD8+ T cells in melanoma patients receiving
      interleukin 12.
AB  - Systemic effects on T-cell-mediated antitumor immunity, on expression of T-cell
      adhesion/homing receptors, and on the promotion of T-cell infiltration of
      neoplastic tissue may represent key steps for the efficacy of immunological
      therapies of cancer. In this study, we investigated whether these processes can
      be promoted by s.c. administration of low-dose (0.5 microg/kg) recombinant human
      interleukin-12 (rHuIL-12) to metastatic melanoma patients. A striking burst of
      HLA-restricted CTL precursors (CTLp) directed to autologous tumor was documented
      in peripheral blood by a high-efficiency limiting dilution analysis technique
      within a few days after rHuIL-12 injection. A similar burst in peripheral CTLp
      frequency was observed even when looking at response to a single tumor-derived
      peptide, as documented by an increase in Melan-A/Mart-1(27-35)-specific CTLp in
      two HLA-A*0201+ patients by limiting dilution analysis and by staining peripheral
      blood lymphocytes (PBLs) with HLA-A*0201-melanoma antigen-A/melanoma antigen
      recognized by T cells (Melan-A/Mart)-1 tetrameric complexes. The CTLp burst was
      associated, in PBLs, with enhanced expression of T-cell adhesion/homing receptors
      CD11a/CD18, CD49d, CD44, and with increased proportion of cutaneous lymphocyte
      antigen (CLA)-positive T cells. This was matched by a marked increase, in serum,
      of soluble forms of the endothelial cell adhesion molecules E-selectin, vascular
      cell adhesion molecules (VCAM)-1 and intercellular adhesion molecules (ICAM)-1.
      Infiltration of neoplastic tissue by CDS+ T cells with a memory and cytolytic
      phenotype was found by immunohistochemistry in eight of eight posttreatment
      metastatic lesions but not in five of five pretreatment metastatic lesions from
      three patients. Increased tumor necrosis and/or fibrosis were also found in
      several posttherapy lesions of two of three patients in comparison with
      pretherapy metastases. These results provide the first evidence that rHuIL-12 can
      boost the frequency of circulating antitumor CTLp in tumor patients, enhances
      expression of ligand receptor pairs contributing to the lymphocyte function
      associated antigen-1/ICAM-1, very late antigen-4/VCAM-1, and CLA/E-selectin
      adhesion pathways, and promotes infiltration of neoplastic lesions by CD8+ memory
      T cells in a clinical setting.

PMID- 10910070
TI  - HER-2/neu is a tumor rejection target in tolerized HER-2/neu transgenic mice.
AB  - HER-2/neu (neu-N) transgenic mice, which express the nontransforming rat proto
      oncogene, develop spontaneous focal mammary adenocarcinomas beginning at 5-6
      months of age. The development and histology of these tumors bears a striking
      resemblance to what is seen in patients with breast cancer. We have characterized
      the immunological responses to HER-2/neu (neu) in this animal model. neu-positive
      tumor lines, which were derived from spontaneous tumors that formed in neu-N
      animals, are highly immunogenic in parental, FVB/N mice. In contrast, a 100-fold
      lower tumor challenge is sufficient for growth in 100% of transgenic animals.
      Despite significant tolerance to the transgene, neu-specific immune responses
      similar to those observed in breast cancer patients can be demonstrated in neu-N
      mice prior to vaccination. Both cellular and humoral neu-specific responses in
      transgenic mice can be boosted with neu-specific vaccination, although to a
      significantly lesser degree than what is observed in FVB/N mice, indicating that
      the T cells involved are less responsive than in the nontoleragenic parental
      strain. Using irradiated whole-cell and recombinant vaccinia virus vaccinations
      we are able to protect neu-N mice from a neu-expressing tumor challenge. T-cell
      depletion experiments demonstrated that the observed protection is T cell
      dependent. The vaccine-dependent neu-specific immune response is also sufficient
      to delay the onset of spontaneous tumor formation in these mice. These data
      suggest that, despite tolerance to neu in this transgenic model, it is possible
      to immunize neu-specific T cells to achieve neu-specific tumor rejection in vivo.
      These transgenic mice provide a spontaneous tumor model for identifying vaccine
      approaches potent enough to overcome mechanisms of immune tolerance that are
      likely to exist in patients with cancer.

PMID- 10910071
TI  - Differences of biodistribution, pharmacokinetics, and tumor targeting between
      interleukins 2 and 15.
AB  - Interleukin-2 (IL-2) and interleukin-15 (IL-15) are T-cell tropic factors that
      share beta and gammac subunits of their receptors on T/NK-cells. Although these
      two cytokines share receptor components, the IL-15Ralpha molecule is expressed
      constitutively by various tissue cells, whereas the IL-2Ralpha expression is
      mostly restricted to activated mononuclear cells. Consequently, we postulated
      that the biodistribution of IL-15 might be different from that of IL-2 and that
      individual alpha chains play an important role in this respect. This study
      investigated the differences between IL-2 and IL-15 in pharmacokinetics,
      biodistribution, and their tumor-targeting abilities. It found that only IL-2
      showed specific binding to a protein, alpha2-macroglobulin, which may be the
      reason that IL-2 displays longer blood clearance than IL-15. Upon injection of
      these cytokines into mice, we observed that IL-15 accumulated significantly more
      than IL-2 in kidney, spleen, and bone. These are all tissues that express IL-15
      receptor alpha but not IL-2 receptor alpha. To evaluate the tumor-targeting
      ability of each cytokine, we used nude mice xenografted with three A431 tumors,
      parental and cells transfected with alpha subunit of the receptor for either IL-2
      or IL-15. When examined using radioiodinated IL-2 or IL-15, each cytokine
      accumulated on the target cells, expressing its respective alpha chain,
      suggesting that the expression of the alpha chains is sufficient to define
      specific biodistribution of IL-2 and IL-15, although these cytokines share the
      beta and yc molecules of their receptors. IL-15 displayed better target-specific
      accumulation and more rapid clearance from the circulation than did IL-2, and
      thus it can be considered to be a novel and unique therapeutic agent.

PMID- 10910072
TI  - Serological cloning of a melanocyte rab guanosine 5'-triphosphate-binding protein
      and a chromosome condensation protein from a melanoma complementary DNA library.
AB  - Characterization of immunogenic human melanoma antigens has been a major focus of
      tumor immunologists over the past two decades, and a broad array of antigens
      recognized by antibodies and T cells in the autologous host has been defined. In
      the present study, a melanoma library was screened by SEREX (serological analysis
      of cDNA expression libraries), and 43 genes were isolated, 2 of which, NY-MEL-1
      and NY-MEL-3, encode novel gene products with differential tissue expression. NY
      MEL-1 encodes a new rab GTP-binding protein, rab38. Among >40 rab proteins, rab38
      has a unique COOH terminus which would allow posttranslational farnesylation and
      palmitoylation, lipid modifications normally occurring in ras proteins but not in
      other rab proteins. It is also the only rab gene showing a predominant mRNA
      expression in melanocytes, a cell-specific expression pattern likely related to
      melanosomal transport and docking. Northern blot analysis showed no detectable
      expression in other normal tissues. Consistent with this lineage specificity,
      rab38 mRNA is expressed in 80-90% of melanoma (17 of 19), but rarely in
      nonmelanocytic malignancies (1 of 16). The second novel gene isolated, NY-MEL-3,
      encodes a mitotic protein highly homologous to the Xenopus chromosome
      condensation protein XCAP-G, designated hCAP-G. Analysis of hCAP-G mRNA
      expression showed highest expression in the testis among normal tissues and
      variable expression in tumor cells, reflecting the proliferative activity in
      these cells. This mitosis-related expression suggests hCAP-G as a possible
      proliferation marker and a potential prognostic indicator in cancer. These
      findings provide further support that SEREX can define biologically significant
      molecules in cancer.

PMID- 10910073
TI  - Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR
      ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21).
AB  - We have studied a patient who presented with clinical features suggestive of
      chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were
      undetectable by reverse transcription-PCR, but a novel reciprocal translocation,
      t(5;10)(q33;q21.2), was seen by standard cytogenetic analysis. Chromosome band
      5q33 contains the gene encoding the platelet-derived growth factor beta receptor
      (PDGFbetaR), the receptor tyrosine kinase that is disrupted by the t(5;7),
      t(5;12), and t(5;14) in myeloid disorders, resulting in the fusion of PDGFbetaR
      to HIP1, TEL/ETV6, and CEV14, respectively. Southern analysis with PDGFbetaR cDNA
      revealed novel bands in patient but not control DNA after digestion with several
      restriction enzymes, indicating that this gene is also targeted by the t(5;10).
      Fluorescence in situ hybridization analysis of chromosome 5 indicated that a
      small inversion at 5q33 had taken place in addition to the interchromosomal
      translocation. The site of the chromosome 10 breakpoint fell within YAC 940e4.
      Because all PDGFbetaR fusions described thus far result in splicing to a common
      exon of this gene, we performed 5'-rapid amplification of cDNA ends PCR on
      patient RNA. Several clones were isolated in which PDGFbetaR fused in frame to
      H4/D10S170, a previously described ubiquitously expressed gene that is fused to
      the ret protein tyrosine kinase to form the PTC-1 oncogene in approximately 20%
      of papillary thyroid carcinomas. The presence of H4-PDGFbetaR chimeric mRNA in
      the patient was confirmed by reverse transcription-PCR; reciprocal PDGFbeta1R-H4
      transcripts were not detected. We conclude that t(5;10)(q33;q21.2) is a novel
      translocation in BCR-ABL-negative chronic myeloid leukemia and that this
      abnormality results in an H4-PDGFbetaR fusion gene. This finding further
      strengthens the association between myeloproliferative disorders and deregulated
      tyrosine kinases.

PMID- 10910074
TI  - Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic
      implications.
AB  - p53 abnormalities constitute the most frequent genetic alterations identified in
      larynx cancers. p53 overexpression in histologically "tumor-free" surgical
      margins correlates with a high recurrence rate. However, only 50-60% of tumors
      overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx
      cancers, and overexpression of eIF4E in histologically "tumor-free" margins
      predicts a significantly higher recurrence. We undertook this study to correlate
      the expression of p53 and eIF4E in the tumors and surgical margins of squamous
      cell cancers of the larynx and to determine their prognostic value. A
      retrospective analysis was performed on 54 patients who underwent surgery for
      squamous cell cancers of the larynx. Patient and tumor characteristics were
      reviewed, and the time to recurrence was noted. Paraffin-embedded sections from
      the tumors and surgical margins were immunostained with antibodies to eIF4E and
      p53, and a qualitative analysis was performed. All 54 patients (100%)
      overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were
      p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All
      6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the
      margins. There was a significant correlation between p53 and eIF4E being positive
      in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the
      25 patients (84%) that recurred, including the 6 patients with p53-positive
      margins, had eIF4E-positive margins. Hence, although the univariate analysis
      showed that nodal status and both eIF4E and p53 expression in the margins were
      significant predictors of recurrence (P < 0.05), in the multivariate analyses
      only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were
      significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the
      disease-free intervals for eIF4E-positive margins were significantly shorter than
      eIF4E-negative margins (P = 0.0007). There was no additional effect to the
      combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of
      eIF4E in the margins appears to be a more sensitive indicator of recurrence and
      may be an earlier event in the process of tumorigenesis than p53.

PMID- 10910075
TI  - High incidence of breast and endometrial neoplasia resembling human Cowden
      syndrome in pten+/- mice.
AB  - PTEN is one of the most commonly mutated tumor suppressor genes in human cancer.
      PTEN mutations have been implicated in the development of a variety of human
      neoplasia, including high-grade glioblastoma, prostate, breast, endometrial, and
      thyroid carcinoma. Germ-line mutations of PTEN cause Cowden's syndrome (CS), a
      multiple hamartoma condition resulting in increased susceptibility for the
      development of cancer. When more than 6 months old, pten+/- mice develop a range
      of tumors, partially resembling the spectrum of neoplasia observed in CS
      patients. One-half (32 of 65) of pten+/- females developed breast tumors, whereas
      all (65 of 65) of the females had endometrial hyperplasia, and there was a high
      incidence (14 of 65) of endometrial cancer. Hamartoamous tumors of the
      gastrointestinal tract, as well as prostate and adrenal neoplasia, were also
      frequently observed. Significantly, the spectrum of neoplasia observed in pten+/-
      mice partially overlaps with the types of tumors frequently detected in CS
      patients. The majority of tumors in pten+/- mice exhibit loss of heterozygosity
      at the pten locus, which indicates the importance for loss of PTEN function in
      tumor formation. Consistent with the role of PTEN in negative regulation of
      PKB/Akt phosphorylation and activity, pten loss of heterozygosity is accompanied
      by hyperphosphorylation of PKB/Akt in tumors. Taken together, our results
      establish pten+/- mice as an excellent animal model system for the investigation
      of PTEN-related hamartoma syndromes, as well as the role of PTEN in breast and
      endometrial carcinogenesis.

PMID- 10910076
TI  - Proliferation-associated SNF2-like gene (PASG): a SNF2 family member altered in
      leukemia.
AB  - To identify genes involved in cell growth and/or apoptosis in leukemia,
      differential display was used to identify mRNAs that showed altered expression
      levels after cytokine withdrawal from the cytokine-dependent MO7e cell line.
      Sequence analysis of one transcript that showed a profound decrease in expression
      after cytokine withdrawal revealed it to be a member of the SNF2 family of
      chromatin remodeling ATPases. This cDNA had a 2514-nucleotide (838-amino acid)
      open reading frame and encoded an additional 230 amino acids at the NH2 terminus
      compared with the murine homologue, lsh, and the human counterpart, Hells. This
      gene locus has been designated SMARCA6 (SWI/SNF2-related, matrix-associated,
      actin-dependent regulator of chromatin, subfamily A, member 6). The highest
      levels of mRNA expression in humans are observed in proliferative tissues such as
      the thymus, testis, and bone marrow. Whereas cytokine withdrawal in MO7e cells
      leads to apoptosis and decreased mRNA expression, growth arrest without the
      induction of apoptosis of MO7e cells also leads to down-regulation of mRNA
      expression, suggesting an association with cell proliferation and not suppression
      of apoptosis. Nuclear localization of this SNF2-like putative helicase is
      dependent on a nuclear localization sequence located in the NH2-terminal region.
      Based on sequence homology to other SNF2-like helicases, the pattern of tissue
      expression, and the association of expression with cell proliferation, we refer
      to the protein product as proliferation-associated SNF2-like gene product [PASG
      (D. W. Lee et al., Blood, 94: 594a, 1999)]. Examination of acute myelogenous
      leukemia and acute lymphoblastic leukemia samples revealed a high frequency of a
      PASG transcript containing an in-frame 75-nucleotide deletion, which codes for a
      conserved motif known to be critical for the transactivation activity of a
      related yeast SWI/SNF polypeptide. These results extend our knowledge of this
      SNF2-like family member and suggest a role for PASG in leukemogenesis.

PMID- 10910077
TI  - Methylation of the androgen receptor minimal promoter silences transcription in
      human prostate cancer.
AB  - Advanced hormone-independent prostate cancer is characterized by a significant
      loss of androgen receptor (AR) expression in 20-30% of the tumors. The
      transcriptional block underlying this phenomenon is not known, but we have
      proposed that methylation of CpG sites in the AR promoter may reversibly
      inactivate transcription of the AR (D. F. Jarrard et al, Cancer Res., 58: 5310
      5314, 1998). In this study, detailed methylation analysis using bisulfite
      sequencing was performed on a series of AR expression-positive and -negative
      prostate cancer cells. We found that methylation of several consensus sequences
      in the AR promoter (from -131 to -121 and +44 to +54) are tightly linked to the
      loss of AR expression in metastatic hormone-independent prostate cancer cell
      lines. These consensus sites of methylation correlate with the minimal promoter
      region critical for AR transcription. In human tissues, no methylation was
      demonstrated in normal or primary prostate cancers that express the AR. Four of
      15 tumors obtained from men who had died from hormone-independent prostate cancer
      demonstrated a significant loss of AR expression immunohistochemically and two
      (50%) of these AR-negative tumors contained AR methylation. We conclude that the
      AR promoter contains specific CpG methylation hot spots that are markers for gene
      silencing. Furthermore, AR methylation may represent a phenotype important in the
      development of hormone independence in a subset of advanced prostate cancer in
      which AR expression is lost. The finding of AR methylation also represents the
      first report of aberrant methylation on an X-linked gene associated with a
      somatic male cancer.

PMID- 10910078
TI  - Mirk protein kinase is a mitogen-activated protein kinase substrate that mediates
      survival of colon cancer cells.
AB  - We have cloned a novel gene mirk (minibrain-related kinase) encoding a protein
      kinase that enables colon carcinoma cells to survive under certain stress
      conditions. Mirk is a mitogen-activated protein kinase substrate but is down
      regulated by activated extracellular signal-regulated kinases (erks) in vivo.
      Mirk contains a PEST region characteristic of rapidly turned over proteins and is
      broken down to a Mr 57,000 form only in the nucleus. In each of three colon
      carcinoma cell lines, mirk levels were increased 20-fold when erk activation was
      blocked by the MEK inhibitor PD98059 in serum-free medium. Addition of IGF-I to
      activate erks blocked this increase. Mirk was stably overexpressed in two colon
      carcinoma cell lines to attain levels seen in colon cancers. Each of five mirk
      transfectants proliferated when switched to serum-free medium and regained rapid
      growth when serum was restored, whereas five vector control transfectants and
      three kinase-dead mutant mirk transfectants did not. mirk mRNA levels were
      elevated in several types of carcinomas, and mirk protein was detected in each of
      seven colon carcinoma cell lines. mirk was expressed at a higher protein level in
      Western blots from three of eight colon cancers compared with paired normal colon
      tissue, suggesting that mirk plays a role in the evolution of a subset of colon
      cancers. mirk is not mutated in colon carcinomas. Mirk may mediate tumor cell
      survival in mitogen-poor environments or early in colon cancer development before
      many autocrine growth factors have been induced.

PMID- 10910079
TI  - Increased tumor necrosis factor-alpha sensitivity of MCF-7 cells transfected with
      NAD(P)H:quinone reductase.
AB  - Evidence from a number of studies suggests that the mechanism by which tumor
      necrosis factor (TNF) kills transformed cells involves oxidative stress.
      NAD(P)H:(quinone acceptor) oxidoreductase (NQO1) is an antioxidant enzyme with
      particular relevance to cancer. The MCF-7 breast cancer cell line was stably
      transfected with rat NQO1 cDNA to determine whether increased NQO1 activity
      alters sensitivity to TNF-induced apoptosis. Five clones, with a range of NQO1
      enzyme activities from 5- to 50-fold greater than the MCF-7 line, and two control
      transfectants were examined. Northern blot hybridization analyses and reverse
      transcription-PCR demonstrated that the increase in NQO1 activity in the
      transfectants was attributable to expression from the transfected rat sequence.
      Based on sulforhodamine B assays for the number of viable cells, the NQO1 clones
      showed increased sensitivity to EO9, an indoloquinone that undergoes bioactive
      reduction by NQO1. Viability studies also demonstrated that the NQO1
      transfectants were significantly more sensitive to TNF than the control
      transfectants or MCF-7 parent. This increased sensitivity could not be explained
      by changes in superoxide dismutase or catalase activity or to increased
      sensitivity to oxidative stress in general, as assessed by response to hydrogen
      peroxide and paraquat treatment. Using dichlorodihydrofluorescein diacetate as a
      probe, we found that the NQO1 transfectants had no difference in baseline level
      of oxidative stress compared to the control cells but did exhibit greater
      intracellular oxidative stress after TNF treatment. We conclude that NQO1 can
      affect the TNF-mediated pathway to apoptosis.

PMID- 10910080
TI  - Identification and fine mapping of a region showing a high frequency of allelic
      imbalance on chromosome 16q23.2 that corresponds to a prostate cancer
      susceptibility locus.
AB  - Linkage to a prostate cancer susceptibility locus was recently reported on
      chromosome 16q23. We now report a region exhibiting a high frequency of allelic
      imbalance (AI) corresponding to this locus in tumors from 51 men diagnosed with
      prostate cancer using the same linked markers. The highest frequency of AI was
      found at markers D16S3096 (45%) and D16S516 (53%) that map to chromosome 16q23.2.
      In addition, 19 of the 51 (37%) prostate tumors showed interstitial AI involving
      one or both of these markers. This result strongly suggests that a candidate
      prostate cancer tumor suppressor gene maps between markers D16S3096 and D16S516.
      We estimate that the distance between these markers is approximately 118 kb using
      a Stanford radiation hybrid panel. We observed a positive association with family
      history (P = 0.048) when comparing those men showing interstitial AI at markers
      D16S3096 and/or D16S516 with those without any imbalance at these two markers.
      Taken together, these data suggest that we have precisely localized a region of
      chromosome 16q23.2 that may harbor a prostate cancer tumor suppressor gene
      implicated in the development of non-familial and possibly familial forms of
      prostate cancer.

PMID- 10910081
TI  - Cadherin switching in human prostate cancer progression.
AB  - The progression of carcinomas is associated with the loss of epithelial
      morphology and a concomitant acquisition of a more mesenchymal phenotype, which
      in turn is thought to contribute to the invasive and/or metastatic behavior of
      the malignant process. Changes in the expression of cadherins, "cadherin
      switching," plays a critical role during embryogenesis, particularly in
      morphogenetic processes. Loss of E-cadherin is reported to be associated with a
      poor prognosis; however, thus far, evidence (R. Umbas, et al., Cancer Res. 54:
      3929-3933, 1994) for up-regulation of other cadherins has only been reported in
      vitro, ie., we have found evidence (M. J. G. Bussemakers et al., Int. J. Cancer,
      85: 446-450, 2000) for cadherin switching in prostate cancer cell lines (up
      regulation of N-cadherin and cadherin-11, two mesenchymal cadherins, in cell
      lines that lack a functional E-cadherin-catenin adhesion complex). Here, we
      report on the immunohistochemical analysis of the expression of N-cadherin and
      cadherin-11 in human prostate cancer specimens. N-cadherin was not expressed in
      normal prostate tissue; however, in prostatic cancer, N-cadherin was found to be
      expressed in the poorly differentiated areas, which showed mainly aberrant or
      negative E-cadherin staining. Cadherin-11 is expressed in the stroma of all
      prostatic tumors, in the area where stromal and epithelial cells are found. In
      addition, cadherin-11 is also expressed in a dotted pattern or at the membrane of
      the epithelial cells of high-grade cancers. In a number of metastatic lesions, N
      cadherin and cadherin-11 are expressed homogeneously. These data raise the
      possibility that cadherin switching plays an important role in prostate cancer
      metastasis.

PMID- 10910082
TI  - Wild-type p53 suppresses angiogenesis in human leiomyosarcoma and synovial
      sarcoma by transcriptional suppression of vascular endothelial growth factor
      expression.
AB  - Our recent studies (R. Pollock et al., Clin. Cancer Res., 4: 1985-1994, 1998; M.
      Milas et al., Cancer Gene Ther., in press, 2000) have shown that the restoration
      of wild-type (wt) p53 enhances cell cycle control in vitro and inhibits the
      growth of human soft-tissue sarcoma in severe combined immunodeficient mice. We
      hypothesized that the antitumor effect of wt p53 overexpression in sarcoma cells
      is attributable not only to enhanced cell cycle control but also to inhibition of
      angiogenesis. We evaluated the effect of restoring wt p53 function on
      angiogenesis in human soft-tissue sarcoma harboring mutant p53. Restoration of wt
      p53 expression in human leiomyosarcoma SKLMS-1 cells that contain mutant p53
      markedly inhibited angiogenesis induced by tumor cells in vivo. Angiogenesis
      assays using an in vivo Matrigel plug assay demonstrated that less
      neovascularization in severe combined immunodeficient mice was observed with
      conditioned medium (CM) from human synovial sarcoma cells expressing wt p53
      compared with CM from human synovial sarcoma cells expressing mutant p53.
      Microvessel density and microvessel counts were lower in tumor xenografts from
      cells containing wt p53 than in tumor xenografts from cells containing mutant
      p53. The growth and migration of murine lung endothelial cells were decreased
      when cells were treated with CM from sarcoma cells expressing wt p53 compared
      with CM from sarcoma cells expressing mutant p53. The introduction of wt p53 into
      sarcoma cells containing mutant p53 significantly reduced the expression of
      vascular endothelial growth factor (VEGF), which is a key mediator of tumor
      angiogenesis. Stimulation of endothelial cell migration by CM from cells
      expressing mutant p53 was significantly reduced after anti-VEGF neutralizing
      antibody was added to the CM. Using luciferase as the reporter of VEGF promoter
      activity, we found that wt p53 inhibited VEGF promoter activity in SKLMS-1 cells.
      Deletion analysis defined an 87-bp region (bp -135 to -48) in the VEGF promoter
      that is necessary for inhibiting VEGF promoter activity by wt p53. The
      transcription factor Sp1 may be involved in the repression of VEGF promoter
      activity by wt p53 in SKLMS-1 cells. These data indicated that wt p53 can
      suppress angiogenesis in human soft-tissue sarcomas by transcriptional repression
      of VEGF expression.

PMID- 10910083
TI  - The value of platelet-derived endothelial cell growth factor as a novel predictor
      of advancement of uterine cervical cancers.
AB  - Serum platelet-derived endothelial cell growth factor (PD-ECGF) in patients with
      uterine cervical cancers revealed a significantly positive correlation with
      clinical stage and tumor size and with the advancement indicators lymph node
      metastasis, parametrial involvement, and vessel permeation in both squamous cell
      carcinomas and adenocarcinomas. The prognosis of the patients with high serum PD
      ECGF was extremely poor, whereas the 36-month survival rate of the other patients
      with low serum PD-ECGF was 81.3% in squamous cell carcinomas and 80.0% in
      adenocarcinomas. Our data indicate that serum PD-ECGF levels reflect the status
      of advancement of uterine cervical cancers and thus may be recognized as a novel
      tumor marker for both squamous cell carcinomas and adenocarcinomas of the uterine
      cervix.

PMID- 10910084
TI  - Teaching hospital?

PMID- 10910085
TI  - The relation between tendency for psychopathology and reduced frontal brain
      volume in healthy people.
AB  - OBJECTIVE: We hypothesized that tendency toward psychopathology is associated
      with lower frontotemporal volumes. BACKGROUND: Although there is considerable
      evidence for structural abnormalities in patients with major psychiatric
      disorders and increased recognition that neural substrates may underlie
      individual differences in personality, there have been no studies in healthy
      people attempting to relate personality to volumetric measures of brain
      structure. METHOD: We used magnetic resonance imaging with an advanced method for
      automated segmentation of cranial compartments to gray matter, white matter, and
      cerebrospinal fluid. We examined the relation between frontal and temporal lobe
      volumes and Minnesota Multiphasic Personality Inventory measures of tendency
      toward psychopathology in 59 healthy individuals. RESULTS: As hypothesized,
      higher scores on the clinical scales were associated with lower average frontal
      lobe volume. When the sample was divided according to sex, however, these
      correlations were significant in men (n = 29) but not in women (n = 30). The
      highest correlation was observed between lower frontal white matter volume in men
      and high schizophrenia scale score (r[27] = -0.59, p <0.001). CONCLUSIONS: The
      findings suggest that personality dimensions in healthy people can be linked to
      neural substrates, which can potentially serve as endophenotypic markers of
      disposition to psychopathology. The sexually dimorphic effects are consistent
      with gender-related differences in the clinical manifestations of psychiatric
      disorders and may suggest sex hormone modulation of the psychopathologic
      processes.

PMID- 10910086
TI  - Quantitative electroencephalographic correlates of psychosis in Alzheimer
      disease.
AB  - OBJECTIVE: We hypothesized that the distinctive neurobiology of Alzheimer disease
      (AD) with psychosis would be reflected in more severe abnormalities in frontal
      and temporal regions on quantitative electroencephalography (QEEG). BACKGROUND:
      Patients with AD and psychosis have more rapid cognitive decline and greater
      pathologic involvement of frontal and temporal cortex than AD patients without
      psychotic features. METHOD: We evaluated brain function using QEEG in a group of
      44 patients who had a diagnosis of probable or possible AD. All patients were
      administered the Mini-Mental State Examination and the Neuropsychiatric Inventory
      to assess psychiatric symptoms, including the presence of hallucinations and
      delusions. Absolute and relative power in patients with and without psychosis
      were compared to determine if there were regional or global QEEG differences in
      these two groups. RESULTS: Patients with psychosis showed greater overall
      absolute and relative delta power but no regional predominance of slowing
      compared with those without psychosis. Those with psychosis had a concomitant
      decrease in relative alpha power. These differences remained after adjustment for
      different dementia severity in the two groups. CONCLUSIONS: This finding suggests
      more severe brain dysfunction in patients with psychosis than in those with
      similar levels of cognitive impairment but without psychosis. The QEEG
      abnormalities were not regionally specific and involved all areas assessed.

PMID- 10910087
TI  - Negative symptoms in patients with major depressive disorder: a preliminary
      report.
AB  - OBJECTIVE: The purpose of this study was to examine negative symptoms (NSs) in
      patients with major depressive disorder (MDD) and their relation to depressive
      symptoms (DSs) and other psychiatric symptoms. BACKGROUND: Features similar to
      NSs were previously described in patients with depression. METHOD: The Hamilton
      Rating Scale for Depression (HRSD), Positive and Negative Symptom Scale (PANSS),
      Scale for the Assessment of Negative Symptoms (SANS), and Mini-Mental State
      Examination were administered to 23 patients with MDD and 10 normal control
      subjects. RESULTS: As expected, the mean scores of the HRSD, SANS, and negative
      symptom subscale of the PANSS of the patients with MDD were significantly higher
      than those of control subjects, validating the clinical significance of NSs as
      well as DSs in MDD patients. Within the MDD group, although measures of NSs were
      intercorrelated, there were no other correlations between the measures. Thus,
      measures of NSs and DSs were not intercorrelated. When the HRSD was divided in
      two subscales, HRSD negative symptom subscale scores but not HRSD depressive
      symptom subscale scores were correlated with PANSS negative symptom subscale and
      SANS total scores as well as with scores on the affective flattening subscale.
      CONCLUSIONS: These results suggest a high level of NSs in patients with MDD,
      which are distinct from positive symptoms of depression and may constitute a
      distinct dimension. Negative symptoms and DSs in MDD may represent separate
      constructs. Further, the HRSD might have possible subscales in MDD as it does in
      schizophrenia.

PMID- 10910088
TI  - Depression, psychomotor retardation, negative symptoms, and memory in
      schizophrenia.
AB  - OBJECTIVE: The purpose of this study was to examine the relations between
      depression, psychomotor retardation, and negative symptoms in schizophrenia as
      well as the specific contribution of each of these factors to memory impairment.
      BACKGROUND: It has been suggested that depression overlaps with negative
      symptomatology in schizophrenia. The relation between psychomotor retardation and
      negative symptomatology has been unclear. METHOD: The Hamilton Depression Rating
      Scale, The Positive and Negative Symptom Scale for Schizophrenia, and Scale for
      the Assessment of Negative Symptoms were used to assess depressive and negative
      symptomatology in a sample of patients with schizophrenia. Verbal memory
      performance was assessed by a free recall test. Two indices of processing speed
      were measured. Correlations among variables were computed. RESULTS: Depression
      score was correlated with the avolition item from the Scale for the Assessment of
      Negative Symptoms and with both measures of processing speed. Negative
      symptomatology was unrelated to processing speed. Memory performance was
      correlated with depression score, slowing of processing speed, and avolition. Its
      correlation with depression score and processing speed remained significant when
      the other factors were partialled out. CONCLUSIONS: Memory performance in
      schizophrenia may be affected by lack of motivation, psychomotor retardation, and
      depression. It is suggested that negative symptoms could be split between a
      volitional component linked to depression and cognitive efficiency and an
      emotional component unrelated to them.

PMID- 10910089
TI  - Neurologic examination abnormalities in schizophrenia with and without a history
      of alcoholism.
AB  - OBJECTIVE: The current investigation examines the impact of a past history of
      alcoholism on neurologic examination abnormalities in schizophrenia (SZ).
      BACKGROUND: Individuals with SZ have a high rate of comorbid alcohol use
      disorders (AUDs), but relatively little is known about the potential adverse
      consequences of alcoholism for neuropsychological and neurologic functioning in
      SZ. Recent evidence suggests consistent but subtle neurocognitive differences
      between groups, with more prominent differences in neurologic examination
      abnormalities. METHOD: Thirty-three male patients with SZ or SZ/AUDs were
      evaluated using a modified Neurologic Evaluation Scale (NES) and ratings for
      positive and negative symptoms. RESULTS: The SZ/AUD group exhibited a greater
      impairment in the Cognitive-Perceptual factor of the Neurologic Evaluation Scale.
      Greater impairment in the tandem-Romberg factor or in motor items was not found,
      nor were groups different based on positive or negative symptoms. CONCLUSIONS: A
      history of alcoholism in SZ is associated with greater overall neurologic
      impairment, particularly in the area of cognitive-perceptual dysfunction, an area
      often found to be impaired in patients with schizophrenia without alcoholism.

PMID- 10910090
TI  - Effects of optokinetically induced rotatory self-motion on spatial perception and
      representation.
AB  - OBJECTIVE: Our aim was to investigate the influence of optokinetically induced
      rotatory self-motion sensation (circular vection [CV]) on asymmetries in real and
      representational space in normal subjects. BACKGROUND: Vestibular and optokinetic
      stimulation (particularly when accompanied by rightward CV) can reduce left-sided
      hemineglect in patients. METHOD: Twenty healthy right-handed men were
      administered a line bisection (LB) task and a stimulus-response compatibility
      task monitoring mental representation of space (the RULER task). The RULER task
      required speeded unimanual decisions ("smaller than 6?" vs. "larger than 6?") to
      foveally presented numbers between 1 and 11. Both tasks were performed in a
      baseline condition (no stimulation) and with full-field optokinetic stimulation
      to induce CV to either side. RESULTS: The bisection marks of both hands were
      shifted significantly to the left during leftward CV, introducing a pseudoneglect
      for the left and right hands. Rightward CV did not influence LB. In the RULER
      task, we found a stimulus-response compatibility, namely, faster right-hand
      responses to large numbers (i.e., 7-11) and faster left-hand responses to small
      numbers (i.e., 1-5). Although optokinetic stimulation did not significantly
      affect subjects' representation of space, the overall pattern of observed
      deviations was strikingly similar to that obtained in LB. CONCLUSIONS:
      Optokinetic stimulation affects healthy subjects' exploration and, to a lesser
      extent, their representation of space. In contrast to previous studies in neglect
      patients and healthy subjects, we found that leftward CV rather than rightward CV
      induced a leftward deviation of the subjective midpoint. This discrepancy is most
      likely a consequence of the exclusively peripheral visual field stimulation in
      our experiment. We suggest that the leftward deviation during rightward CV
      described in former studies may be due to the cuing effect of the leftward moving
      dots in the central visual field. In the absence of these central cues, the
      direction of CV seems to be the main determining factor for observed hemispatial
      effects.

PMID- 10910091
TI  - Developmental instability predicts individual variation in verbal memory skill
      after caffeine ingestion.
AB  - OBJECTIVE: To determine the mediating effects of developmental instability on
      individual differences in response to caffeine. BACKGROUND: Individual variation
      of drug effects might reflect broad genomic factors as well as the direct effects
      of specific alleles. The current study tested the hypothesis that individual
      differences in developmental instability, in part determined by genomic
      characteristics, would predict individual variation in the magnitude of caffeine
      induced verbal memory deficits. Minor physical anomalies and fluctuating
      asymmetry were used as measures of developmental instability. METHOD: One hundred
      participants were (1) administered one version of the Rey Auditory Verbal
      Learning Test; (2) given a dose of caffeine determined by body weight (3 mg/kg);
      (3) assessed for minor physical anomalies and fluctuating asymmetry; and (4)
      given an alternate randomized version of the Rey Auditory Verbal Learning Test.
      RESULTS: Consistent with predictions, a composite measure of developmental
      instability predicted the magnitude of caffeine-induced memory decrements.
      CONCLUSIONS: These results may have important implications for the genetic
      underpinnings of individual differences in drug effects.

PMID- 10910092
TI  - Abnormal neuropsychological findings are not necessarily a sign of cerebral
      impairment: a matched comparison between chronic fatigue syndrome and multiple
      sclerosis.
AB  - OBJECTIVE: The aim of this study was to assess the potential impact of effort in
      comparative studies assessing neurocognitive dysfunction in patients with and
      without a neurologic diagnosis. BACKGROUND: It was hypothesized that a subgroup
      within a group of patients with prominent neurocognitive complaints but without a
      neurologic diagnosis would have impaired performance on a task originally
      designed to detect malingering. METHOD: We compared the neuropsychological
      performance of a group of 40 patients with a definite diagnosis of multiple
      sclerosis (MS) with that of 67 patients with chronic fatigue syndrome (CFS). The
      Amsterdam Short-Term Memory Test, a forced-choice memory task, served as measure
      to detect submaximal effort. In addition, we administered a regular
      neuropsychological task generally considered to be sensitive for cognitive
      deterioration. RESULTS: Compared with the MS group (13%), a larger proportion of
      the matched CFS group (30%) obtained scores indicative of reduced effort. In
      contrast, the proportions of patients scoring below the cutoff value on a
      conventional neuropsychological test did not differ significantly (17% of MS
      patients and 16% of CFS patients). CONCLUSIONS: The results obtained raise the
      question of to what extent abnormal test findings in the absence of documented
      neurologic impairment should be interpreted as a sign of cerebral impairment. The
      suggestion has been made to screen more often for biased results in comparative
      research studies so as to enhance valid interpretation of neuropsychological
      findings.

PMID- 10910093
TI  - A program for neuropsychological investigation of deep brain stimulation (PNIDBS)
      in movement disorder patients: development, feasibility, and preliminary data.
AB  - OBJECTIVE: This technical report and feasibility study propose a standardized
      method for collecting neuropsychological data in patients undergoing the deep
      brain stimulation (DBS) procedure. BACKGROUND: Programs for standardizing motor
      data collected in studies investigating surgical therapies for Parkinson disease
      are already widely used (e.g., Core Assessment Program for Intracerebral
      Transplantations). The development and rationale for the proposed Program for
      Neuropsychological Investigation of Deep Brain Stimulation (PNIDBS) are outlined,
      and support for the feasibility of these methodologies is provided via
      preliminary data. METHOD: The PNIDBS includes a core battery of
      neuropsychological tests that assesses a wide range of cognitive functions
      (attention, language, visuospatial, memory, and executive) as well as depression.
      Using the PNIDBS, three Parkinson disease and two dystonia patients were
      evaluated at baseline and after surgery, once with stimulation off and once with
      stimulation on. RESULTS: Patients with severe motor disabilities were able to
      complete the PNIDBS. These preliminary data suggest that the DBS procedure as a
      whole had a minimal impact on cognitive functioning in most patients studied.
      There was also some evidence that the one patient who showed cognitive decline
      after the DBS procedure had demographic and clinical characteristics that may
      have put him at risk for this decline. CONCLUSIONS: The procedures in the PNIDBS
      were systematically developed and are feasible to execute. The relatively brief
      core battery has multiple versions and can be supplemented to meet individual
      investigator needs. By evaluating the components of the DBS procedure (electrode
      placement and stimulation), the PNIDBS can address clinical questions regarding
      the cognitive effects of the DBS procedure as well as investigate basic
      scientific issues regarding how different cognitive functions are affected when
      subcortical-prefrontal circuits are manipulated by the DBS procedure.

PMID- 10910094
TI  - Hypersexuality and hemiballism due to subthalamic infarction.
AB  - OBJECTIVE: A 70-year-old right-handed man presented with a subthalamic infarction
      followed by persistent hypersexuality and hemiballism. A lacunar infarction 1 cm
      in diameter was observed on magnetic resonance imaging. We hypothesized that
      metabolic abnormalities would be detected in cortical areas related to his
      neurobehavioral symptoms. BACKGROUND: Statistical validation of the regional
      metabolic changes that may relate to neuropsychiatric symptoms has been elusive.
      Relating metabolic changes to neuropsychiatric symptoms is especially important
      in unique neurobehavioral cases. METHOD: Quantitative fluorodeoxyglucose positron
      emission tomography was obtained for a single-subject comparison with scans from
      60 healthy subjects. RESULTS: Substantial glucose hypometabolism (p <0.001,
      uncorrected; [df = 56]) was identified in the subthalamic nucleus at the site of
      the lacunar infarction. Hypermetabolism (p <0.01) was identified within the basal
      forebrain and temporal lobes, anterior cingulate and medial prefrontal cortices
      (areas previously associated with hypersexuality), and striatum (p <0.001)
      ipsilateral to the stroke (areas known to relate to hemiballism). CONCLUSIONS:
      Single-subject statistical parametric mapping may improve our understanding of
      unique neurobehavioral cases.

PMID- 10910095
TI  - Oncogenic transformation of cells by a conditionally active form of the protein
      kinase Akt/PKB.
AB  - The Akt/PKB protein kinase is implicated in the control of cell cycle progression
      and the suppression of apoptosis in cancer cells. Here we describe the use of a
      conditionally active form of Akt/PKB (M+ Akt:ER*) to study the ability of this
      protein to influence biological processes that are central to the process of
      oncogenic transformation of mammalian cells. Activation of M+ Akt:ER* in Rat1
      cells elicited alterations in cell morphology and promoted anchorage-independent
      growth in agarose with high efficiency. Consistent with these observations,
      activation of M+ Akt:ER* suppressed the apoptosis of Rat1 cells that occurs after
      the detachment of these cells from extracellular matrix. Furthermore, activation
      of M+ Akt:ER* was sufficient to promote the progression of quiescent Rat1 cells
      into the S and G2-M phases of the cell cycle. In accord with this is the
      observation that activation of M+ Akt:ER* led to decreased expression of the
      cyclin-dependent kinase inhibitor p27Kip1 with a concomitant increase in cyclin
      dependent kinase-2 activity. Perhaps surprisingly, activation of M+ Akt:ER* or
      expression of a constitutively active form of Akt led to rapid activation of
      MAP/ERK Kinase (MEK) and the extracellular signal-regulated kinase (ERK)/mitogen
      activated protein (MAP) kinases in Rat1 cells. However, pharmacological
      inhibition of MEK by PD098059 did not inhibit the morphological alterations of
      Rat1 cells that occur after M+ Akt:ER* activation. These data suggest that M+
      Akt:ER* can activate a number of pathways in Rat1 cells, leading to significant
      alterations in a number of biological processes. The conditional transformation
      system described here will allow further elucidation of the ability of Akt to
      contribute to both the normal response of cells to mitogenic stimulation and the
      aberrant proliferation observed in cancer cells.

PMID- 10910096
TI  - Specific inhibition of growth factor-stimulated extracellular signal-regulated
      kinase 1 and 2 activation in intact cells by electroporation of a growth factor
      receptor-binding protein 2-Src homology 2 binding peptide.
AB  - Activation of the Ras pathway is central to mitogenesis by a variety of growth
      factors such as the epidermal growth factor, platelet-derived growth factor, or
      hepatocyte growth factor. Ras activation requires the function of adaptors such
      as growth factor receptor-binding protein 2, which can bind either directly or
      indirectly through Src homology 2 domains to the activated receptor. To examine
      the role of the Src homology 2 domain of growth factor receptor-binding protein 2
      in the mitogenic response triggered by these growth factors, we introduced a
      peptide (PVPE-phosphono-methylphenylalanine-INQS) that can selectively bind this
      domain into mouse, rat, or human cells growing on conductive indium-tin oxide
      coated glass by in situ electroporation. Cells were subsequently stimulated with
      growth factors and assessed for activation of a downstream target, extracellular
      signal-regulated kinase (ERK) 1/2, by probing with antibodies specific for its
      activated form. Electrodes and slides were configured to provide
      nonelectroporated control cells side by side with the electroporated ones, both
      growing on the same type of indium-tin oxide-coated glass surface. The data
      demonstrate that the peptide can cause a dramatic inhibition of epidermal growth
      factor or platelet-derived growth factor-mediated ERK1/2 activation and DNA
      synthesis in vivo, compared with its control phenylalanine-containing
      counterpart. In contrast, the peptide had a very limited effect on hepatocyte
      growth factor-triggered ERK1/2 activation and DNA synthesis. These results
      demonstrate the potential of the in situ electroporation approach described here
      in the study of the coupling of activated receptor tyrosine kinases to the ERK1/2
      cascade.

PMID- 10910097
TI  - Src family kinase activity is required for Kit-mediated mitogen-activated protein
      (MAP) kinase activation, however loss of functional retinoblastoma protein makes
      MAP kinase activation unnecessary for growth of small cell lung cancer cells.
AB  - Small cell lung cancer (SCLC) is characterized by multiple genetic alterations
      that include inactivation of the retinoblastoma protein (Rb), the establishment
      of several autocrine loops including that induced by coexpression of stem cell
      factor (SCF) and Kit, and the ectopic expression and activation of Src family
      kinases. Previous studies have shown that Lck associates with, and becomes
      activated by, Kit after SCF stimulation of SCLC cells. In the present study, we
      have demonstrated that PP1, a pharmacological inhibitor of Src kinases, blocked
      SCF-mediated activation of mitogen-activated protein (MAP) kinase, but it also
      inhibited Kit activation. However, MAP kinase activation was more sensitive than
      Kit activation to the effects of PP1. Overexpression of Lck reduced the
      sensitivity of MAP kinase activation to PP1 without altering the sensitivity of
      Kit activation, which suggested a role for Lck in SCF-mediated MAP kinase
      activation. Inducible expression of a dominant negative Lck inhibited MAP kinase
      activation in a dose-dependent manner, which confirmed that Src family kinase
      activity is required for SCF-induced MAP kinase activation. The growth of cells
      that expressed dominant negative Lck was unaffected, however, despite the
      inhibition of MAP kinase. Growth was also unaffected by the inhibition of the MAP
      kinase pathway using PD 98059, but sensitivity to the MAP/extracellular signal
      regulated kinase kinase inhibitor could be partially restored by expression of
      wild-type Rb. Therefore, MAP kinase activation seems to be dispensable for the
      growth of SCLC only in the absence of Rb expression. These data suggest that the
      SCF/Kit autocrine loop, through activation of Lck and subsequently MAP kinase,
      and the mutational inactivation of Rb contribute to the loss of G1-S phase
      checkpoint regulation during the pathogenesis of SCLC. Furthermore, the data
      demonstrate that, in established SCLC cell lines, proliferative signal
      transduction initiated by Kit is mediated by pathways other than the classic MAP
      kinase pathway.

PMID- 10910098
TI  - p53-mediated differentiation of the erythroleukemia cell line K562.
AB  - The tumor suppressor gene p53 can mediate both apoptosis and cell cycle arrest.
      In addition, p53 also influences differentiation. To further characterize the
      differentiation inducing properties of p53, we overexpressed a temperature
      inducible p53 mutant (ptsp53Val135) in the erythroleukemia cell line K562. The
      results show that wild-type p53 and hemin synergistically induce erythroid
      differentiation of K562 cells, indicating that p53 plays a role in the molecular
      regulation of differentiation. However, wild-type p53 did not affect phorbol 12
      myristate 13-acetate-dependent appearance of the megakaryocyte-related cell
      surface antigens CD9 and CD61, suggesting that p53 does not generally affect
      phenotypic modulation. The cyclin-dependent kinase inhibitor p21, a
      transcriptional target of p53, halts the cell cycle in G1 and has also been
      implicated in the regulation of differentiation and apoptosis. However,
      transiently overexpressed p21 did neither induce differentiation nor affect the
      cell cycle distribution or viability of K562 cells, suggesting that targets
      downstream of p53 other than p21 are critical for the p53-mediated
      differentiation response.

PMID- 10910099
TI  - Cell cycle control during liver development in the rat: evidence indicating a
      role for cyclin D1 posttranscriptional regulation.
AB  - Hepatocytes are capable of marked changes in proliferation in response to various
      physiological and pathophysiological stimuli. Although the changes in adult
      hepatocyte growth regulation that accompany reduction of liver mass, liver
      injury, and liver carcinogenesis have come under intense scrutiny, the regulation
      of hepatocyte growth during the latter stages of development is largely
      uncharacterized. We have examined hepatic cell cycle control in the developing
      rat. Analysis of term (fetal day 21) liver and cultured, term hepatocytes
      revealed G0-G1 growth-arrested cells relative to preterm (fetal day 19) liver and
      isolated hepatocytes. G1 cyclin-dependent kinase (CDK) activity was correlated
      with growth arrest at term in both in vivo and in vitro studies. The decline in
      CDK activity at term could not be attributed to a change in CDK protein content.
      Rather, the decline in CDK activity was associated with a concomitant decline in
      cyclin D1 protein content. However, cyclin D1 mRNA levels did not correlate with
      protein levels. Cyclin D1 mRNA was present at a higher level in adult livers, in
      which cyclin D1 protein was absent, than in fetal livers. We also examined the
      phosphorylation (activation) state of p38 mitogen-activated protein kinase, a
      potential hepatocyte-growth regulator and modulator of cyclin D1 content. p38
      activity was inversely related to cyclin D1 content during liver development and
      regeneration. These data indicate that a posttranscriptional mechanism regulating
      cyclin D1 content is involved in the temporary hepatocyte growth arrest seen in
      the perinatal period and in the maintenance of adult hepatocytes in a quiescent
      state. We speculate that this posttranscriptional regulation may be downstream
      from the p38 mitogen-activated protein kinase pathway.

PMID- 10910100
TI  - The role of p21 in interferon gamma-mediated growth inhibition of human breast
      cancer cells.
AB  - IFN-gamma-mediated growth inhibition requires signal transducers and activators
      of transcription (STAT)-1 activation and may require induction of the cyclin
      dependent kinase inhibitor p21. Using an electrophoretic mobility shift assay, we
      identified STAT1 activation after IFN-gamma treatment in breast cancer cell
      lines. Accordingly, IFN-gamma inhibited proliferation of monolayer cultured MCF-7
      and MDA-MB-231 breast cancer cells. Interestingly, IFN-gamma inhibited anchorage
      independent growth of MCF-7 cells but had no effect on MDA-MB-231 colony
      formation. Because p21 has been shown to play a role in anchorage-independent
      growth and is a transcriptional target of STAT1, we examined the effect of IFN
      gamma on p21 mRNA. We found that IFN-gamma induced p21 mRNA in MCF-7 cells but
      not in MDA-MB-231 cells. Furthermore, IFN-gamma induced activation of a p21
      promoter-luciferase reporter construct that contained the STAT1-inducible element
      in MCF-7 cells, but not in MDA-MB-231 cells. IFN-gamma treatment resulted in
      increased p21 protein in MCF-7 cells, whereas MDA-MB-231 cells did not appear to
      express detectable p21, even after IFN-gamma treatment. However, in MDA-MB-231
      cells, p21 protein was detected only after proteosome inhibition, suggesting that
      degradation may be responsible for the undetectable level of p21 in these cells,
      despite the abundant mRNA levels. Finally, focus formation of MDA-MB-231 cells
      was inhibited by overexpression of p21. In conclusion, STAT1 activation does not
      appear to be sufficient for IFN-gamma-mediated growth inhibition. Furthermore,
      the role of p21 appears to be complex because monolayer growth inhibition occurs
      in the absence of p21, but anchorage-independent growth inhibition may require
      p21. Breast cancer cells may provide a unique model for further study of IFN
      gamma signaling.

PMID- 10910101
TI  - Localization of heme oxygenase-2 and modulation of cGMP levels by carbon monoxide
      and/or nitric oxide in the retina.
AB  - Heme oxygenase-2 (HO-2) synthesizes carbon monoxide (CO), a modulator of soluble
      guanylate cyclase (sGC). To examine this signal transduction pathway in the
      retina, we immunocytochemically localized HO-2, and investigated the effects of
      CO on cGMP levels. In turtle, HO-2-like immunoreactivity (-LI) was in all
      photoreceptors, some amacrine cells, and in numerous bipolar and ganglion cells.
      HO-2-LI colocalized with sGC activity in many cells. In rat, HO-LI was found only
      in the inner retina, in ganglion and amacrine cells. In turtle, stimulation with
      CO alone primarily increased cGMP-LI in bipolar cells in the visual streak.
      Stimulation with a combination of CO and nitric oxide (NO) dramatically increased
      cGMP-LI throughout the retina, in comparison to the smaller increases seen with
      NO or CO alone. These data suggest that CO is an endogenous modulator of the
      sGC/cGMP signaling pathway in many retinal neurons, and can dramatically amplify
      NO-stimulated increases in cGMP.

PMID- 10910102
TI  - Inhibitory basket cell synaptic input to layer IV simple cells in cat striate
      visual cortex (area 17): a quantitative analysis of connectivity.
AB  - In the absence of a direct and specific marker for basket cells, the aim of this
      paper was to use available data to estimate the density of basket cell synaptic
      input to smooth and spiny neurons within layer IV of cat striate visual cortex
      (area 17). A linear quantitative analysis of layer IV basket cell connectivity
      data suggests that on average basket cells (1) comprise 25-35% of all GABAergic
      neurons in layer IV (3552-4736 cells mm(-3)), (2) account for 30-41% of all
      putative inhibitory dendritic synapses of layer IV spiny stellate cells (145-195
      synapses cell(-1)) and a similar proportion of layer IV basket cells (25-37%, 71
      107 synapses cell(-1)), and (3) provide each layer IV spiny cell with 13-45 axons
      and each layer IV basket cell with 6-29 axons. These estimates suggest that
      basket cells may be less common and provide a smaller proportion of the dendritic
      synaptic input to layer IV spiny and smooth neurons than previously thought. In
      addition, the analysis indicates that a layer IV spiny stellate cell may receive
      on average as many synapses and axons from layer IV basket cells as from lateral
      geniculate relay cells. Based on this potential numerical similarity, a
      geniculate-basket synaptic pairing in a spine-shaft microcircuit is hypothesized.
      This microcircuit could implement a type of local (dendritic) push-pull
      interaction underlying subfield antagonism.

PMID- 10910103
TI  - Effect of monocular deprivation on NMDAR1 immunostaining in ocular dominance
      columns of the marmoset Callithrix jacchus.
AB  - We previously showed that immunoreactivity to N-Methyl-D-aspartate (NMDA)
      receptors in primary visual cortex of Callithrix jacchus is regulated by visual
      activity during the second and third postnatal months (Fonta et al., 1997). The
      purpose of the present study was to show that the columnar pattern of high and
      low NMDAR1 immunoreactivity observed in monocularly deprived animals corresponds
      to ocular dominance columns linked to the nondeprived and deprived eye,
      respectively. We compared cortical distribution of NMDAR1 receptors and the
      projection zones of thalamic afferents, revealed by transneuronal transport of
      tritiated proline, in 2-month-old, either monocularly deprived or control,
      marmosets. The data show that ocular dominance columns exist in 2-month-old
      marmosets and that a 2-week monocular deprivation by means of eyelid suture leads
      to a modification of the thalamo-cortical afferents organization. Experiments of
      neuronal tracing and immunohistochemistry performed on the same animals
      demonstrated that cortical domains with decreased NMDAR1 level correspond to the
      deprived eye columns. These investigations, coupled to the previous results,
      strongly suggest that the NMDA receptors, regulated by visual activity, are
      involved in the refining of ocular dominance columns in the primary visual cortex
      of juvenile marmoset.

PMID- 10910104
TI  - Visual adaptation modulates a potassium conductance in retinular cells of the
      crayfish.
AB  - Crayfish photoreceptors exhibit a voltage-dependent potassium conductance, G(K),
      that is generally similar to the delayed rectifier channel described in neurons
      and other arthropod retinular cells. G(K) activation (i.e. the apparent
      threshold, Vth) occurs near the resting potential and G(K) is substantially
      reduced by 25 mM extracellular tetraethylammonium (TEA) and by intracellular Cs+
      injections. Light exposure, sufficient to reduce visual sensitivity 100-fold,
      increases Vth (shifts it in the depolarizing direction) by about 20 mV. The light
      dependent change in Vth does not depend upon the corresponding increase
      (depolarization) of the steady-state membrane potential nor does it depend upon
      inward calcium currents. Vth is slightly influenced by fluctuations in Ko
      associated with the light-elicited currents. During light exposure Ko (measured
      with K+-sensitive electrodes) increases by 2.1 mM (equivalent to an 8 mV increase
      in E(K)). This increase in E(K) makes only a modest contribution to the light
      dependent change in Vth as determined by perfusion with high potassium salines.
      Intracellular calcium injections increase Vth by 10 to 20 mV and reduce visual
      sensitivity by 5- to 10-fold. The results imply that during exposure to high
      levels of illumination, K+ currents at the steady-state membrane potential are
      diminished by a calcium-dependent change in G(K) gating and, to a smaller degree,
      by a reduced K+ concentration gradient. It is notable that Ca2+ appears to
      inhibit both G(K) and the light-elicited conductance from both inside and outside
      the plasma membrane. As a consequence of the light-dependent change in Vth, G(K)
      makes only modest contributions to the changes in sensitivity and speed normally
      associated with light adaptation. These functions are regulated by the
      transduction pathway and are revealed at the resting potential in the time course
      and magnitude of the light-elicited currents.

PMID- 10910105
TI  - Suppression outside the classical cortical receptive field.
AB  - The important visual stimulus parameters for a given cell are defined by the
      classical receptive field (CRF). However, cells are also influenced by visual
      stimuli presented in areas surrounding the CRF. The experiments described here
      were conducted to determine the incidence and nature of CRF surround influences
      in the primary visual cortex. From extracellular recordings in the cat's striate
      cortex, we find that for over half of the cells investigated (56%, 153/271), the
      effect of stimulation in the surround of the CRF is to suppress the neuron's
      activity by at least 10% compared to the response to a grating presented within
      the CRF alone. For the remainder of the cells, the interactions were minimal and
      a few were of a facilitatory nature. In this paper, we focus on the suppressive
      interactions. Simple and complex cell types exhibit equal incidences of surround
      suppression. Suppression is observed for cells in all layers, and its degree is
      strongly correlated between the two eyes for binocular neurons. These results
      show that surround suppression is a prevalent form of inhibition and may play an
      important role in visual processing.

PMID- 10910106
TI  - GABA responses of rod bipolar cells in rabbit retinal slices.
AB  - GABAergic responses of rabbit rod bipolar cells were reexamined by using whole
      cell recordings in the superfused slice preparation to determine if there is
      GABA(C) receptor input to their axon terminal and to characterize the
      contribution that GABA(A) and GABA(C) receptors make to the total GABA current on
      the axon terminals of these cells. Pharmacological agents specifically blocking
      GABA(A) and GABA(C) receptor currents demonstrated that 37% of the GABA-activated
      current was blocked by either the GABA(A) antagonists bicuculline or SR-95531,
      whereas the remaining 63% of the GABA current was blocked by a mixture of
      bicuculline and the GABA(C) antagonist TPMPA. This indicated that GABA(C)
      receptors were present on the axon terminal of the rabbit rod bipolar cell and
      that they were responsible for mediating the bicuculline insensitive GABA
      current.

PMID- 10910107
TI  - Cannabinoid receptors on goldfish retinal bipolar cells: electron-microscope
      immunocytochemistry and whole-cell recordings.
AB  - Cannabinoid CB1 receptors are distributed throughout the CNS and interact with
      GABA, glutamate, and dopamine systems. Cannabinoids have effects on the visual
      system, some of which may have a retinal component, particularly the enhancement
      of photosensitivity. We used immunocytochemistry and whole-cell recording to
      study cannabinoids in the goldfish retina. Immunoblots of an antiserum against
      amino acids (1-14) of the rat CB1 receptor produced a single band in goldfish
      retina at about 70 kDa. Light microscope immunocytochemistry of CB1 receptor
      immunoreactivity (CB1R-IR) revealed intense staining of Muller cells and weaker
      staining of ON bipolar cells (verified with double labeling with PKC-IR) and the
      outer and inner plexiform layers. Ultrastructural analysis revealed that CB1R-IR
      was localized intracellularly as well as on the plasma membrane of photoreceptor
      terminals, bipolar cell terminals and, rarely, amacrine cell boutons. Membrane
      associated CB1R-IR was restricted to cone pedicles at sites removed from the
      synaptic ribbon. Regarding bipolar cells, membrane-associated CB1R-IR was found
      at 93% of the synaptic terminals in sublamina b (ON-type) and only at 33% of the
      synaptic terminals in sublamina a (OFF-type). Whole-cell recordings from large ON
      type Mb bipolar cells showed that the delayed rectifier (I(K(V))) was rapidly and
      reversibly inhibited by 1 microM of the cannabinoid agonists CP 54490 and (+)-WIN
      55212-2, effects blocked completely by the antagonist SR 141716A (1 microM).
      Inhibition of I(K(V)) in the Mb bipolar cells by cannabinoids should result in a
      more tonic ON response to increments of light. As such, cannabinoids may play a
      role in modulating the temporal aspects of signaling in the retina.

PMID- 10910109
TI  - Response profiles to texture border patterns in area V1.
AB  - Cells in area V1 of the anesthetized macaque monkey were stimulated with large
      texture patterns composed of homogeneous regions of line elements (texels) with
      different orientations. To human observers, such patterns appear to segregate,
      with the percept of sharp boundaries between texture regions. Our objective was
      to investigate whether the boundaries are reflected in the responses of single
      cells in V1. We measured responses to individual texels at different distances
      from the texture border. For each cell, patterns of optimally or orthogonally
      orientated texels were adjusted so that only one texel fell into the receptive
      field and all other texels fell in the visually unresponsive regions outside. In
      37 out of 156 neurons tested (24%), texels immediately adjacent to a texture
      border evoked reliably larger responses than identical texels farther away from
      the border. In 17 neurons (11%), responses to texels near the border were
      relatively reduced. Border enhancement effects were generally stronger than
      border attenuation effects. When tested with four different border configurations
      (two global orientations and two edge polarities), many cells showed reliable
      effects for only one or two configurations, consistent with cells encoding
      information about the orientation of the texture border or its location with
      respect to the segmented region. Across the sample, enhancement effects were
      similar for all texture borders. Modulation by the texture surround was
      predominantly suppressive; even the responses near texture borders were smaller
      than those to a single line. We compared these results with the results of a
      popout test in which the line in the receptive field was surrounded by
      homogeneous texture fields either orthogonal or parallel to the center line. The
      patterns of response modulation and the temporal onset of differential responses
      were similar in the two tests, suggesting that the two perceptual phenomena are
      mediated by similar neural mechanisms.

PMID- 10910108
TI  - Photoreceptors, visual pigments, and ellipsosomes in the killifish, Fundulus
      heteroclitus: a microspectrophotometric and histological study.
AB  - The photoreceptor layer of F. heteroclitus was examined by light and electron
      microscopy. We identified four cone visual pigments with maximum absorbance
      (lambda(max)) in the UV (363 nm), short (400 nm), middle (463 nm), and long (563
      nm) wavelength regions of the spectrum and a rod visual pigment that peaked in
      the middle wavelengths (503 nm). Electron-dense bodies, ellipsosomes and
      pseudoellipsosomes, were present in the distal ellipsoids of long/middle (L/M)
      and long/long (L/L) wavelength double cones and in single short wavelength (S)
      cones, respectively. The light absorption of ellipsosomes indicated the presence
      of reduced cytochrome-c with the highest optical densities found in the M members
      of L/M double cones. By contrast, S cones contained pseudo-ellipsosomes which had
      very low optical density. UV cones were present everywhere as part of square or
      row mosaics in the retina of F. heteroclitus. Cone packing was on average higher
      for locations in the upper half of the retina while the highest cone density was
      found in the centro-ventral retina. An analysis of potential quantum catches for
      each cone type as a function of retinal sector and underwater irradiance
      characteristics revealed higher overall quantum catches for cones in the upper
      retina when the light field was assumed homogeneous, and higher quantum catches
      for cones in the lower retina when downwelling, horizontal, and upwelling
      irradiances were considered separately. At dusk, quantum catch was highest for M
      cones and the contribution to the overall retinal quantum catch by UV and S cones
      was much greater than during daylight hours. We propose that UV and S cones may
      be used to detect targets of interest against the background irradiance sensed by
      double cones.

PMID- 10910110
TI  - Distribution of the alpha1 subunit of the GABA(A) receptor on midget and parasol
      ganglion cells in the retina of the common marmoset Callithrix jacchus.
AB  - The inhibitory neurotransmitter gamma aminobutyric acid (GABA) has been shown to
      influence the responses of ganglion cells in the mammalian retina. Consistently,
      GABA(A) receptor subunits have been localized to different ganglion cell types.
      In this study, the distribution of the alpha1 subunit of the GABA(A) receptor on
      the dendrites of midget and parasol ganglion cells was investigated
      quantitatively in the retina of a New World monkey, the marmoset. Ganglion cells
      were injected with Neurobiotin in a live in vitro retinal whole-mount
      preparation. Retinal pieces were then processed with an antibody against the
      alpha1 subunit of the GABA(A) receptor. Strong punctate immunoreactivity
      indicative of synaptic localization is present in the ON and OFF sublamina of the
      inner plexiform layer. Many of the immunoreactive puncta coincide with the
      dendrites of both midget and parasol ganglion cells. Immunoreactive puncta are
      present on distal and proximal dendrites of ON and OFF cells of both ganglion
      cell types. On average, parasol cells show a slight increase in the spatial
      density of immunoreactive puncta with distance from the soma, whereas the density
      of immunoreactive puncta on midget cells stays even. Parasol ganglion cells show
      a slightly higher average density of immunoreactive puncta (0.083 puncta/microm
      dendrite) than midget cells (0.054 puncta/microm dendrite).

PMID- 10910111
TI  - A temporal model for early vision that explains detection thresholds for light
      pulses on flickering backgrounds.
AB  - A model is presented for the early (retinal) stages of temporal processing of
      light inputs in the visual system. The model consists of a sequence of three
      adaptation processes, with two instantaneous nonlinearities in between. The three
      adaptation processes are, in order of processing of the light input: a divisive
      light adaptation, a subtractive light adaptation, and a contrast gain control.
      Divisive light adaptation is modeled by two gain controls. The first of these is
      a fast feedback loop with square-root behavior, the second a slow feedback loop
      with logarithm-like behavior. This can explain several aspects of the temporal
      behavior of photoreceptor outputs. Subtractive light adaptation is modeled by a
      high-pass filter equivalent to a fractional differentiation, and it can explain
      the attenuation of low frequencies observed in ganglion cell responses. Contrast
      gain control in the model is fast (Victor, 1987), and can explain the decreased
      detectability of test signals that are superimposed on dynamic backgrounds. We
      determine psychophysical detection thresholds for brief test pulses that are
      presented on flickering backgrounds, for a wide range of temporal modulation
      frequencies of these backgrounds. The model can explain the psychophysical data
      for the full range of modulation frequencies tested, as well as detection
      thresholds obtained for test pulses on backgrounds with increment and decrement
      steps in intensity.

PMID- 10910112
TI  - Neuronal and microglial response in the retina of streptozotocin-induced diabetic
      rats.
AB  - This study reports Muller cell and neuronal changes and microglial reaction in
      streptozotocin-induced diabetic rats. Glial fibrillary acidic protein (GFAP)
      immunoreactivity was largely confined to astrocytes in the nerve fiber layer
      (NFL) and ganglion cell layer (GCL) in control rats. In diabetic rats especially
      those killed after 12 months, GFAP immunostaining could be traced along the
      entire length of Muller cell processes, extending from the inner to the outer
      limiting membrane. With the antibody neuronal nuclei, immunopositive cells were
      located in the GCL and the inner part of the inner nuclear layer (INL) in both
      diabetic and age-matched control rats. In diabetic rats, labelled cells were
      reduced in both layers being more marked in the INL. In age-matched control rats,
      OX42-immunoreactive microglial cells were distributed mainly in the NFL and GCL;
      some cells were localized in the inner plexiform layer, but rarely in the outer
      plexiform layer (OPL). Beginning 1 month after diabetes, the microglial cells
      appeared hypertrophic. Furthermore, microglial number as estimated from cell
      counts in different layers of the retina was significantly increased, with the
      occurrence of some cells in the OPL at 4 months. At 14 and 16 months, reactive
      microglial cells were detected in the outer nuclear layer and photoreceptor
      layer. Present results suggest that microglial reaction in induced diabetes was
      elicited by neuronal cell loss in both GCL and INL as well as by some pathologic
      changes affecting the photoreceptors.

PMID- 10910114
TI  - Expression of glycine and the glycine transporter Glyt-1 in the developing rat
      retina.
AB  - Previous studies show that glycine transporter-1 (glyt-1) is a consistent
      membrane marker of adult retinal neurons that are likely to release glycine at
      their synaptic terminals (Pow, 1998; Vaney et al., 1998; Pow & Hendrickson,
      1999). The current study investigated when glyt-1 immunoreactivity appeared in
      the postnatal rat retina, and whether all glycine-containing neurons also
      labelled for glyt-1. Ganglion cells, horizontal cells, and photoreceptors showed
      transient labelling. Many cells in the ganglion cell layer are immunoreactive for
      both glycine and glyt-1 at postnatal day (Pd) 1 but both are minimal by Pd5.
      Transient immunoreactivity for both glyt-1 and glycine was observed in
      presumptive horizontal cells between Pd5 and Pd10. At Pd1 many cells in the outer
      part of the retina which resembled immature photoreceptors were heavily labelled
      for glycine, but did not express glyt-1 these disappeared at older ages. These
      findings suggest diverse mechanisms and transient roles for glycine in the
      developing rat retina. In the adult rat retina, a subpopulation of amacrine cells
      are prominently immunoreactive for both glycine and glyt-1. These cells labelled
      for glycine at Pd1, but did not express significant levels of glyt-1 until Pd5.
      Processes from these amacrine cells did not reach the inner half of the inner
      plexiform layer until Pd10-14. Bipolar cells became glycine-IR between Pd10 and
      Pd14, but consistently lacked any glyt-1 immunoreactivity. This temporal pattern
      of labelling strongly indicates that bipolar cells label for glycine when gap
      junctions become functional between glycine/glyt-1 immunoreactive amacrine cells
      and cone bipolar cells.

PMID- 10910113
TI  - Second messenger pathways involved in up-regulation of an L-type calcium channel.
AB  - Catfish cone horizontal cells contain a voltage-gated L-type calcium channel that
      is modulated by activation of metabotropic glutamate receptors (mGluRs).
      Activation of group I mGluRs with the mGluR I agonist, (S)-3,5
      dihydroxyphenylglycine [(S) 3,5-DHPG], potentiated peak calcium current
      amplitude, shifted the membrane potential corresponding to peak current activity,
      and widened the calcium current's activation range. In this study, we have
      examined the mechanisms linking activation of the mGluRs with "up-regulation" of
      calcium current activity. Under whole-cell voltage-clamp conditions favoring
      expression of the L-type calcium current, we provide evidence that activation of
      mGluRs initiate the diacylglyceral (DG) second messenger pathway to activate
      protein kinase C (PKC) and up-regulate calcium channel activity. This evidence
      was based on results using a number of PKC activators and inhibitors. PKC
      activators mimicked the effect of (S) 3,5-DHPG on calcium current activity. Up
      regulation of the calcium channel by PKC activators or (S) 3,5-DHPG was
      eliminated if PKC inhibitors were present. These results also demonstrated that
      activation of group I mGluRs were linked to a pertussis toxin sensitive G
      protein. When the GTP analog, guanosine 5-0-(3-thiotriphosphate (GTPgammaS), was
      allowed to diffuse into voltage-clamp cells, up-regulation of the calcium channel
      occurred and mimicked the effect of (S) 3,5-DHPG. However, when pertussis toxin
      (PTX) was allowed to diffuse into the cell along with GTPgammaS, GTPgammaS failed
      to modulate calcium current activity. IP3 (inositol 1,4,5 triphosphate) is a
      second product produced by activation of group I mGluRs. Once formed, IP3 can
      trigger calcium release from IP3-sensitive intracellular stores. To determine if
      the IP3 second messenger system was involved in up-regulation of calcium channel,
      (S) 3,5-DHPG was applied to voltage-clamped cone horizontal cells containing
      different concentrations of the calcium buffer, EGTA. Low concentrations of EGTA
      failed to buffer calcium released from intracellular stores. In the presence of
      low EGTA concentrations, (S) 3,5-DHPG's enhancement of the calcium current
      amplitude was reduced. Inhibition of the calcium current amplitude in low
      concentrations of EGTA was eliminated in the presence of the intracellular
      calcium store blocker, heparin. These results suggest that both the DG and IP3
      second messenger pathways are involved in modulation of the voltage-gated calcium
      channel in catfish cone horizontal cells. The DG pathway up-regulates the voltage
      gated calcium channel activity whereas calcium released from IP3 intracellular
      stores inhibits peak current amplitude.

PMID- 10910116
TI  - Manganese exposures in Toronto during use of the gasoline additive,
      methylcyclopentadienyl manganese tricarbonyl.
AB  - A year-long population-weighted study of personal exposures to particulate matter
      (PM2.5) was conducted in Toronto while the manganese-containing additive,
      methylcyclopentadienyl manganese tricarbonyl (MMT), was present in gasoline at an
      average level of 11.9 mg Mn/l, which was higher than the maximum of 8.3 mg Mn/l
      allowed in the U.S. In this study, 925 three-day personal samples of PM2.5 (air
      concentration of aerosol with an aerodynamic diameter of less than 2.5 microm)
      were collected, along with a record of participants' occupations, personal
      habits, surroundings, and activities during sampling. Stationary samples of PM2.5
      were collected indoors and outdoors at a subset of participants' homes over the
      same 3-day periods. Three-day samples of PM2.5 were also collected at fixed
      locations. Personal exposures to PM2.5 were highly influenced by exposure to
      tobacco smoke, and were poorly correlated with outdoor levels (Kendall's
      tau=0.13). The mean concentration of PM2.5 in homes (21 microg/m3) was
      significantly higher than the mean outdoor level (15 microg/m3). By contrast, the
      mean PM2.5 Mn concentration (air concentration of Mn in PM2.5) was higher
      outdoors (9.7 ng/m3) than indoors (5.5 ng/m3). Other than from tobacco smoke,
      there were no indications of significant indoor sources of PM2.5 Mn in homes. The
      most important predictor of exposure to PM2.5 was time spent in the subway, and a
      high level (428 ng/m3) of PM2.5 Mn was measured in the subway. The source of this
      Mn was hypothesized to be friction erosion of subway rails. Small, but
      statistically significant correlations were present between personal exposures to
      PM2.5 Mn and several traffic-related variables (time spent in transit, in a motor
      vehicle, near a roadway with traffic, and in a parking garage). However, in a
      stepwise regression that adjusted for weather and personal activities, time in a
      motor vehicle was the only traffic-related variable significantly associated with
      PM2.5 Mn, and it was only the 10th most important personal activity variable in
      the final model. Concentrations of PM2.5 Mn were higher at two fixed locations
      than outside of participants' homes, which were likely further from high traffic
      areas than the fixed sites. Likewise, outdoor and fixed site samples collected
      during periods that included weekend days contained lower air concentrations of
      Mn than samples collected during weekdays when traffic was heavier. On the other
      hand, the monthly average concentration of Mn in gasoline was negatively
      correlated with both outdoor and personal PM2.5 Mn, which suggests that traffic
      related sources of Mn other than MMT may be present. After omitting participants
      with exposure to Mn from certain identifiable non-MMT sources (subway riders,
      metal workers and persons exposed to tobacco smoke), the average (median)
      personal exposure of the remaining 325 participants to PM2.5 Mn was reduced from
      14 ng/m3 (8.5 ng/m3 ) to 8.3 ng/m3 (7.0 ng/m3). Potential sources of this
      residual Mn exposure include, in addition to MMT, naturally occurring Mn in the
      earth's crust, other occupational exposure, airborne release of Mn from
      industrial operations, and friction erosion of Mn from steel-containing products.
      Taken together, these facts (elimination of participants with Mn exposure from
      known non-MMT sources reduced average exposures by 40%, the existence of multiple
      non-MMT sources of the remaining Mn exposure, and the negative correlation
      between MMT usage and PM2.5 Mn) suggest that the preponderance of personal Mn
      exposure was from non-MMT sources.

PMID- 10910115
TI  - Ozone dose-response effects of varied equivalent minute ventilation rates.
AB  - While it is well known that exercise minute ventilation (V(E)) results in greater
      pulmonary function and subjective symptoms (SS) responses upon exposure to a
      given ozone (O3) dose, the magnitude of V(E) increase to produce a significant
      forced expiratory volume in 1 s (FEV1.0) response compared to that observed at a
      lower exercise V(E) for the same O3 concentration and exposure time is unclear,
      especially in prolonged (i.e., >2 h) exposures. Further, in prolonged exposures,
      the relationship of body size to FEV1.0 response to a given O3 exposure dose has
      not been systematically examined. In the present study, 30 young adults were
      exposed on four occasions for 6 h (during a 6.6-h period) to constant 03 levels
      of zero (filtered air, FA) or 0.12 parts per million (ppm). At the latter
      concentration, exercise V(E) was varied in exposures to 17, 20, and 23 l min(-1)
      m(-2) of BSA, respectively, for each individual to achieve an equivalent
      ventilation rate, EVR). In the FA exposure, EVR was 23 l min(-1) m2. Percent
      changes in FEV1.0 for the three 0.12 ppm O3 exposures were significantly greater
      than that for FA, but did not differ significantly from each other. For the 6.6-h
      exposures, exercise EVR at or in excess of 17 l min(-1) m(-2), SS values were
      significantly greater than those observed for the FA protocol. Further, SS values
      at 6.6 h of exposure to 0.12 ppm O3 for the exercise EVR of 23 l min(-1) m(-2)
      protocol were significantly greater than for the 0.12 ppm O3 exercise EVR of 17 l
      min(-1) m(-2) protocol. To achieve a widened EVR, two 1-h exposures to 0.30 ppm
      O3 with continuous exercise (CE) at a level necessitating an EVR of 17 and
      approximately 34 l min(-1) m(-2), respectively, were completed by each subject.
      All postexposure pulmonary function and SS responses were significantly greater
      for the higher 1-h EVR protocol. In all exposures with significant O3-induced
      changes in FEV1.0 and SS, it was found that the smaller subjects who exercised at
      the lowest absolute V(E) had significantly smaller responses than did the larger
      subjects. These results strongly suggest that for the O3 concentrations and
      exposure durations used in this study, the effect of V(E) on O3-induced FEV1.0
      and SS responses is not body-size-dependent.

PMID- 10910118
TI  - Personal exposure assessment studies may suffer from exposure-relevant selection
      bias.
AB  - We evaluated exposure-relevant selection bias within the framework of a study on
      personal air pollution exposure, using traffic data as exposure proxy. Based on
      random samples of 3000 (Basel) and 2532 (Helsinki) persons, 50 and 250 subjects,
      respectively, were recruited for direct monitoring and 250 (Basel, Helsinki) for
      indirect monitoring. In Basel, participants of direct monitoring as compared to
      non-participants were more likely to live at streets with low traffic volume (49%
      below 1st quartile vs. 27%). Adjusted for sex, age and nationality, an increase
      of 100 cars per hour was associated with 14% less participation (odds ratio (OR):
      0.861; 95% CI: 0.731, 1.007). Although in Helsinki, traffic volume was neither
      significantly related to participation in direct nor indirect monitoring, the
      point estimates indicate a tendency to decreased participation with increasing
      traffic intensity at home. We conclude that selection bias regarding exposure
      relevant characteristics is likely to occur when recruiting participants for
      studies including demanding personal exposure assessment. Correction for factors
      routinely collected may not fully account for exposure-relevant bias. This is of
      particular importance when using exposure data for modelling population exposure
      distributions, whereas in epidemiological studies, a reduced range of exposure
      must not a priori distort the exposure-response relationship.

PMID- 10910117
TI  - Modeling methylene chloride exposure-reduction options for home paint-stripper
      users.
AB  - Home improvement is a popular activity, but one that can also involve exposure to
      hazardous substances. Paint stripping is of particular concern because of the
      high potential exposures to methylene chloride, a solvent that is a potential
      human carcinogen and neurotoxicant. This article presents a general methodology
      for evaluating the effectiveness of behavioral interventions for reducing these
      risks. It doubles as a model that assesses exposure patterns, incorporating user
      time-activity patterns and risk-mitigation strategies. The model draws upon
      recent innovations in indoor air-quality modeling to estimate exposure through
      inhalation and dermal pathways to paint-stripper users. It is designed to use
      data gathered from home paint-stripper users about room characteristics, amount
      of stripper used, time-activity patterns and exposure-reduction strategies (e.g.,
      increased ventilation and modification in the timing of stripper application,
      scraping, and breaks). Results indicate that the effectiveness of behavioral
      interventions depends strongly on characteristics of the room (e.g., size, number
      and size of doors and windows, base air-exchange rates). The greatest simple
      reduction in exposure is achieved by using an exhaust fan in addition to opening
      windows and doors. These results can help identify the most important information
      for product labels and other risk-communication materials.

PMID- 10910119
TI  - Time budgets of infants for exposure assessment: a methodological study.
AB  - The paper presents the application of the microenvironment approach for
      collection of time budget data to assess exposure of people to indoor air
      pollution. The aim of the study was to objectively test the hypothesis that
      exposure to pollutants from combustion of low-grade cooking fuels is a
      significant risk factor for acute respiratory infection (ARI) in infants (0-12
      months). One of the specific objectives of this study was to estimate, in the
      winter season, the integrated daily exposure of infants and their mothers to
      respirable suspended particles (RSPs) and carbon monoxide (CO). The daily
      integrated exposure was estimated by splitting the day into parts called
      microenvironments identified by the mobility patterns of the infants and mothers.
      These were so determined such that the spatial variation in the concentration of
      pollutants during these microenvironments is believed to be relatively
      insignificant under the given conditions, based on results of past studies and
      subjective judgement. The time spent in these microenvironments by the infants
      and mothers was determined by preparing time budgets. Very little correlation was
      found between the two methods of measurement (recall method and direct
      observation using a stopwatch) for the total time spent in cooking or time
      actually near the stove. It was observed that infants in houses using kerosene
      were near the stove for a duration that is 68% of the total cooking duration,
      while for infants in wood-using households this duration is only 44% (on the
      basis of the recall method, these numbers are 84% and 63% respectively). The
      infants spent more time in the indoor noncooking microenvironment irrespective of
      the fuel and slum type.

PMID- 10910120
TI  - PCB exposure in utero and via breast milk. A review.
AB  - A review of the literature was conducted to investigate the importance to
      offspring of in utero and breast milk polychlorinated biphenyl (PCB) exposure.
      All reports that we could identify (n=25) were included, representing 16 study
      populations. Tissue-specific PCB concentrations in human placenta, breast milk,
      maternal blood and cord blood were compared to determine accumulation ratios
      between tissue compartments. On a lipid basis, the highest concentration of PCB
      in placenta (5027 ng/g fat) was 2.8 times higher than the highest concentration
      of PCB in breast milk ( 1770 ng/g fat). While there are limitations with regard
      to quantitation methods and statistical methods utilized by the reviewed studies,
      our results suggest that PCBs may be capable of crossing the placenta to a
      greater extent than previously believed. Future studies of PCB body burden in the
      perinatal period should include placenta, breast milk, maternal and cord blood
      specimens. In order to compare PCB concentrations in various tissues and with
      other studies, concentrations should be determined on a lipid basis.

PMID- 10910121
TI  - Relationships among personal, indoor, and outdoor fine and coarse particle
      concentrations for individuals with COPD.
AB  - This study characterizes the personal, indoor, and outdoor PM2.5, PM10, and PM2.5
      10 exposures of 18 individuals with chronic obstructive pulmonary disease (COPD)
      living in Boston, MA. Monitoring was performed for each participant for six
      consecutive days in the winters of 1996 or 1997 and for six to twelve days in the
      summer of 1996. On each day, 12-h personal, indoor, and outdoor samples of PM2.5
      and PM10 were collected simultaneously. Home characteristic information and time
      activity patterns were also obtained. Personal exposures were higher than
      corresponding indoor and outdoor concentrations for all particle measures and for
      all seasons, except for winter indoor PM2.5-10 levels, which were higher than
      personal and outdoor levels. Higher personal exposures may be due to the
      proximity of the individuals to particle sources, such as cooking and cleaning.
      Indoor concentrations were associated with both outdoor concentrations and
      personal exposures (as determined by individual least square regression
      analyses), with associations strongest for PM2.5. Indoor PM2.5 concentrations
      were significantly associated with outdoor and personal levels for 12 and 15 of
      the 17 individuals, respectively. Both the strength and magnitude of the
      associations varied by individual. Also, personal PM2.5, but not PM2.5-10,
      exposures were associated with outdoor levels, with 10 of the 17 subjects having
      significant associations. The strength of the personal-outdoor association for
      PM2.5 was strongly related to that for indoor and outdoor levels, suggesting that
      home characteristics and indoor particulate sources were key determinants of the
      personal-outdoor association for PM2.5. Air exchange rates were found to be
      important determinants of both indoor and personal levels. Again, substantial
      interpersonal variability in the personal-outdoor relationship was found, as
      personal exposures varied by as much as 200% for a given outdoor level.

PMID- 10910122
TI  - The spatial and temporal variation of particulate matter within the home.
AB  - Numerous epidemiological studies have found associations between ambient
      particulate matter and adverse health outcomes. The importance of indoor
      particles has also been recognised since people spend an average of 90% of their
      time indoors. In order to better understand exposure to particles this study was
      carried out to provide data on the characteristics of airborne particulate matter
      found inside homes in the UK. Forty-eight-h measurements were taken at 10 houses
      during the summer of 1999. Particulate matter with a 50% cut-off efficiency at an
      aerodynamic diameter of 2.5 microm (PM2.5) and total suspended particulate (TSP)
      mass concentrations were measured gravimetrically in the kitchen and living room
      of each home. Concurrent continuous measurements of particle number
      concentrations over eight different aerodynamic diameter size ranges were made
      with an optical particle counter. Occupants were asked to complete a time
      activity diary and a short questionnaire relating to various housing
      characteristics for the 48-h period. The volunteers spent approximately 60% of
      their time at home indoors. The geometric mean concentration of TSP over the 48 h
      was 32 microg/m3 in the kitchen and 41 microg/m3 in the living room. The
      geometric mean concentration of PM2.5 was 13 microg/m3 in the kitchen (integrated
      over the entire 48-h period) and 12 microg/m3 in the living room (integrated over
      the time the volunteer was present in the house) with a range of 5 to 77
      microg/m3. The continuous measurements showed large variability over the day as a
      result of activities such as cooking and smoking and the patterns were similar in
      the kitchen and the living room. A good correlation of both mass and mean number
      concentration between rooms indicated a high degree of spatial uniformity.

PMID- 10910123
TI  - Gene transfer into chicken embryos as an effective system of analysis in
      developmental biology.
AB  - Chicken embryos have been used as a model animal in developmental biology since
      the time of comparative and experimental embryology. Recent application of gene
      transfer techniques to the chicken embryo increases their value as an
      experimental animal. Today, gene transfer into chicken cells is performed by
      three major systems, lipofection, electroporation and the virus-mediated method.
      Each system has its own features and applicability. In this overview and the
      associated four minireviews, the methods and application of each system will be
      presented.

PMID- 10910124
TI  - Misexpression of genes in brain vesicles by in ovo electroporation.
AB  - Transfection to living chick embryos in ovo by electroporation has been recently
      developed. In this mini-review, misexpression in brain vesicles is introduced. To
      transfect, expression plasmid is inserted in the brain vesicle, and the square
      pulse of 25 V, 50 ms was charged five times. The translation product of the
      transfected gene is detected 2 h after electroporation, and reaches the peak at
      24 h after electroporation. Transfection is so effective that this method is
      contributing greatly to the study of the molecular mechanisms of morphogenesis.

PMID- 10910125
TI  - Applications of microelectroporation for studies of chick embryogenesis.
AB  - A technique by which genes can be introduced into the cells and tissues of
      developing embryos has great potential for studying the roles of genes during
      vertebrate embryogenesis. The 'microelectroporation' technique, in which DNA is
      introduced into cells within a restricted area of developing chick embryos with
      high reproducibility, was developed by the authors. In this review, the
      advantages and applications of this microelectroporation technique for
      developmental studies and functional analysis of genes in chick embryos is
      discussed.

PMID- 10910126
TI  - Application of efficient and specific gene transfer systems and organ culture
      techniques for the elucidation of mechanisms of epithelial-mesenchymal
      interaction in the developing gut.
AB  - Epithelial-mesenchymal interactions are very important in the development of the
      vertebrate gut. In the avian embryonic stomach (proventriculus), expression of
      embryonic chick pepsinogen (ECPg) gene, which is specific to developing glandular
      cells in stomach epithelium, is regulated by mesenchymal influence. Molecular
      mechanisms of tissue-specific transcriptional regulation of the ECPg gene and the
      molecular nature of the mesenchymal signals were analyzed using a combination of
      the classic organ culture system and gene transfer strategies. In the present
      review, three methods for the introduction of DNA into tissues are described:
      lipofection, electroporation and retroviral infection, and characteristics of
      each system are discussed.

PMID- 10910127
TI  - Gene transfer into chicken embryos by retrovirus vectors.
AB  - While chickens have many properties that are advantageous for embryological
      studies, their genetic analysis has been restricted. However, by using retrovirus
      vector systems in combination with classical techniques of experimental
      developmental biology, it has recently become possible to analyze the function of
      genes involved in the development of this organism. Avian retrovirus vectors are
      unique in that they can be divided into two categories: replication-competent and
      replication-defective (replication-incompetent). By choosing the vectors
      correctly, there are many experimental applications of these vectors such as
      induction of constitutive (or regulated) gene expression in a restricted region
      of tissues, organs and embryos; cell lineage analysis; and formation of
      concentration gradients of morphogens in micromass cultures. In this paper,
      several retrovirus vectors available for the chicken will be introduced and their
      applications in developmental biology will be reviewed.

PMID- 10910128
TI  - Synergistic effects of FGF and non-ridge ectoderm on gene expression involved in
      the formation of the anteroposterior axis of the chick limb bud in cell culture.
AB  - Skeletal patterning of the vertebrate limb is controlled by the zone of
      polarizing activity (ZPA), apical ectodermal ridge (AER) and dorsal ectoderm. In
      the present study, to understand the involvement of fibroblast growth factor
      (FGF) and non-ridge ectoderm in anteroposterior (AP) axis formation, gene
      expression in chick limb bud mesenchymal cells in culture was investigated by
      reverse transcription-polymerase chain reaction and in situ hybridization. It was
      found that Shh expression was locally maintained in the mesenchymal cells
      underneath and near non-ridge ectoderm in coculture with the posterior
      mesenchymal cells and non-ridge ectoderm in the presence of FGF-4 by in situ
      hybridization. In Shh-expressing anterior limb bud mesenchymal cells cultured
      with non-ridge ectoderm, it was also discovered that Bmp-2 was activated in the
      presence of FGF-2, -4 and -8, while Hoxd-13 was activated in the presence of FGF
      4 and that FGF-2 had a similar effect but FGF-8 did not. This result indicates
      that Hoxd-13 activation by SHH depends on non-ridge ectoderm and FGF-2 or FGF-4,
      and that there may be a difference in the effect on AP axis formation of the limb
      bud between FGF-2, -4 and -8. Possible roles of these genes and signal molecules
      in AP pattern formation are discussed.

PMID- 10910129
TI  - Analysis of cartilage maturation using micromass cultures of primary
      chondrocytes.
AB  - A micromass culture (MM-C) system of primary immature chondrocytes for functional
      analysis of soluble factors involved in the maturation step of cartilage was
      previously developed. Ectopically expressed BMP-2 was shown to induce the
      expression of the Ihh and Noggin genes. Here it is demonstrated that, upon longer
      culture, secreted bone morphogenetic protein-2 (BMP-2) further promotes the
      maturation step as judged by the induction of type X collagen and BMP-6
      expression, which are known to be detectable in the later phase of cartilage
      maturation. Induction of all of these genes by secreted BMP-2 was not inhibited
      by ectopic expression of parathyroid hormone-related peptide (PTHrP) induced by
      retrovirus vector infection, although the same virus vector showed strong
      inhibitory effects on the expression of type X collagen gene or alkaline
      phosphatase activity in mature chondrocytes. These results suggest that the
      maturation-promoting activity exhibited by BMP-2 is dominant over the suppressive
      effect of PTHrP in immature chondrocytes. When the BMP-6 gene was introduced into
      the same virus vector as that used for BMP-2, it induced the same sets of genes
      (Ihh, Noggin, type X collagen and endogenous BMP-6) as BMP-2 did. These results
      also suggest that BMP-6 would autonomously maintain and/or promote a later stage
      of chondrocytic maturation.

PMID- 10910131
TI  - Expression and characterization of Xenopus type I collagen alpha 1 (COL1A1)
      during embryonic development.
AB  - A cDNA encoding Xenopus type I collagen alpha 1 (Xenopus COL1A1) has been
      isolated from an ovary cDNA library. The COL1A1 cDNA is approximately 5.7 kb
      pairs and encodes 1447 amino acids. The putative COL1A1 polypeptide shares high
      identities of amino acid sequence with other vertebrate COL1A1 proteins. The
      level of Xenopus COL1A1 transcripts was increased markedly in the posterior
      region of the embryo at the tail-bud stage, then gradually spread to the anterior
      region. Histological observations of the tail-bud embryos showed that COL1A1 was
      mainly expressed in the inner layer of the posterior dorsal epidermis exposed to
      the somite mesoderm, except for in the dorsal fin. Less intense signals were also
      detected in the outer layer of the dorsal epidermis and dermatome. The expression
      of COL1A1 was increased in posteriorized embryos resulting from treatment with
      retinoic acid but decreased in hyper-dorsalized embryos resulting from lithium
      chloride treatment. These results suggest that COL1A1 is a major component of the
      dorsal dermis exposed to the somite in Xenopus embryos, but its expression is not
      related to the temporal sequence of somite segregation.

PMID- 10910130
TI  - A Drosophila Winged-helix nude (Whn)-like transcription factor with essential
      functions throughout development.
AB  - A Drosophila gene, Dwhn (Drosophila whn-like), encoding a putative
      transcriptional regulator with a DNA binding domain similar to that of mouse
      Winged-helix nude (Whn) was cloned. Analyses of the phenotypes produced by a
      hypomorphic mutation and transgene expression suggested a role in cell fate
      decision during the differentiation of the compound eye, wing veins and bristles.
      During embryonic development, Dwhn expression started ubiquitously followed by
      more restricted expression in striking contrast to the expression patterns of
      other Drosophila forkhead (fkh) family genes whose local expression correlate
      well to their roles as local homeotic genes. This broad expression may correspond
      to the multiple defects in embryos homozygous for strong alleles, such as defects
      in the formation of central and peripheral nervous systems, germ band retraction,
      head involution, and dorsal closure. The DNA binding specificity of Dwhn differed
      from that of Whn despite the strong sequence conservation in the DNA binding
      domain. Dwhn is the first invertebrate Whn-like transcriptional regulator, and
      should provide insights into the basic functions and evolution of the whn family
      genes.

PMID- 10910132
TI  - IFN-gamma induces apoptosis in mouse embryonic stem cells, a putative mechanism
      of its embryotoxicity.
AB  - It has been reported that interferon (IFN)-gamma should inhibit in vitro mouse
      embryo growth by direct cell toxicity. However, the mechanism involved has not
      been clearly established. In the present study, this question was addressed using
      the embryonic stem (ES) cell model. It was found that IFN-gamma, induces a dose
      dependent apoptosis in ES cells, as assessed by trypan-blue staining, by Annexin
      V labeling and DNA analysis, Moreover, IFN-gamma treatment cooperates with Fas
      mediated apoptosis, a phenomenon that has been recently reported. As Bcl-2
      oncoprotein functions as a death repressor molecule in an evolutionarily
      conserved cell death pathway, its expression was analyzed by flow cytometry. It
      was demonstrated that Bcl-2 is expressed in ES cells. When compared to untreated
      ES cells, IFN-gamma-treated, apoptotic cells expressed a lower Bcl-2 level and a
      normal level of Fas, whereas surviving cells expressed a normal level of Bcl-2
      but a lower Fas expression. Altogether, these data suggest that IFN-gamma may
      influence early mouse embryo development by promoting apoptosis, which may
      constitute a novel mechanism of IFN-gamma embryotoxicity.

PMID- 10910133
TI  - Reduction of intramembranous particles in the periacrosomal plasma membrane of
      boar spermatozoa during in vitro capacitation: a statistical study.
AB  - Membrane remodeling in the periacrosomal plasma membrane (PAPM) of boar
      spermatozoa during incubation in capacitation medium was examined by the freeze
      fracture technique. In the preservation medium (PM) group, the major small (about
      8 nm) intramembranous particles (IMP) and the minor large (> 10 nm) IMP were
      distributed evenly in the PAPM. The IMP-free area increased during capacitation.
      To correct the IMP-free area, arithmetically redistributed (ARD)-IMP density was
      used for statistical analysis. In the PM group, the mean density +/- SD of large
      IMP was 379 +/- 64 and 266 +/- 58/microm2, and that of small IMP was 1450 +/- 155
      and 672 +/- 252/microm2 in protoplasmic (P) and external (E) faces, respectively.
      During capacitation, the significant (P < 0.01) reduction of large IMP density
      was encountered only in the E face of a few incubation groups, while that of the
      small IMP density occurred in the P face by 2 h. Consequently, reduction of the
      total IMP density of both faces was not significant in the large IMP, but it was
      significant (P < 0.01) in the small IMP. One-fifth of the total small IMP density
      reduced by 2 h. Filipin-sterol complexes (FSC) were numerous in the PAPM, and FSC
      free areas also increased during capacitation. The mechanism of IMP-free area
      formation and the behavior of the small IMP in the PAPM during capacitation were
      discussed in relation to membrane stability.

PMID- 10910134
TI  - A diffusible factor involved in MAP-kinase ERK2-regulated development of
      Dictyostelium.
AB  - Mitogen-activated protein (MAP)-kinase extracellular signal regulated kinase
      (ERK2) is essential for regulation of the intracellular cyclic adenosine
      monophosphate (cAMP) level in Dictyostelium. The mutant lacking ERK2, erk2-null,
      is arrested at the pre-aggregation stage, but develops into a fruiting body in a
      mixed population of wild-type and mutant cells. This fact implies that wild-type
      cells provide a certain factor that is missing in erk2-null. It was clarified
      that both wild-type strains KAx3 and Ax2 secreted a diffusible factor that
      enables erk2-null to develop. The fruiting body formed from erk2-null cells was
      smaller than that formed by the wild-type cells and consisted of a small sorus
      supported by a slender stalk with a single row of vacuolated stalk cells. The
      resulting spores were able to germinate and multiply on a bacterial lawn, but
      they were unable to develop unless the factor was provided. After 8 h of
      starvation, wild-type cells started to secrete the factor, which had a molecular
      mass of less than 3 kDa and was heat stable. The effect of this factor could not
      be mimicked by either cAMP or folate. Adenylyl cyclase A and cell surface cAMP
      receptors cAR1 and cAR3 were all indispensable components for the factor to
      function. Considering the molecular mass and the mode of action, this factor
      could be a novel one. Possible targets of this factor are discussed in terms of
      cAMP-dependent protein kinase activation.

PMID- 10910135
TI  - Non-dependence of cyclin E/Cdk2 kinase activity on the initiation of oocyte
      maturation in goldfish.
AB  - Cdk2 kinase activity increases during oocyte maturation but neither cyclin A nor
      B is associated with Cdk2 in mature oocytes in goldfish. As a potential Cdk2
      partner in meiosis, a cyclin E homolog was isolated from a goldfish oocyte cDNA
      library. A monoclonal antibody was raised against bacterially produced full
      length goldfish cyclin E. Both cyclin E and Cdk2 were already present in immature
      oocytes and their protein levels did not change remarkably during oocyte
      maturation. Cyclin E formed a complex mainly with Cdk2 just at the time of
      germinal vesicle breakdown (GVBD) in association with the increase in Cdk2 kinase
      activity, although a fraction of cyclin E bound to Cdk(s) other than Cdk2 and
      Cdc2. Ectopic activation of cyclin E/Cdk2 by the injection of cyclin E messenger
      RNA (mRNA) into immature oocytes did not induce maturation-promoting factor (MPF)
      activation and GVBD. Furthermore, inhibition of cyclin E/Cdk2 kinase activity by
      the injection of p21SDI1 into the oocytes treated with 17alpha,20beta-dihydroxy-4
      pregnen-3-one had no effect on MPF activation and GVBD. These results indicate
      that cyclin E/Cdk2 kinase activity is insufficient and unnecessary for initiating
      goldfish oocyte maturation.

PMID- 10910136
TI  - Intravascular and endobronchial DNA delivery to murine lung tissue using a novel,
      nonviral vector.
AB  - Gene transfer to the lung can be achieved via either the airway or the pulmonary
      vasculature. We evaluated gene transfer and expression by intravascular and
      endobronchial routes, using DNA complexed with G9 PAMAM dendrimer or naked
      plasmid DNA. Intravascular tail vein delivery of dendrimer-complexed pCF1CAT
      plasmid resulted in high levels of transgene expression in the lung at 12 and 24
      hr, followed by a second peak of expression 3 to 5 days after administration.
      After intravenous administration of the complexes, CAT expression was never
      observed in organs other than the lung. There were only minimal levels of CAT
      protein expressed in the lung after intravenous administration of naked plasmid
      DNA. Repeated intravascular doses of the dendrimer-complexed plasmid,
      administered four times at 4-day intervals, maintained expression at 15-25% of
      peak concentrations achieved after the initial dose. Endobronchial delivery of
      naked pCF1CAT plasmid produced significant amounts of CAT protein in the lung.
      Comparison of intratracheal and intranasal routes resulted in similar expression
      levels of CAT in the lung and trachea. However, in juxtaposition to vascular
      delivery, intranasal delivery of dendrimer-complexed plasmid DNA gave lower
      levels of CAT expression than that observed with naked plasmid DNA. In situ
      localization of CAT enzymatic activity suggested that vascular administration
      seemed to achieve expression in the lung parenchyma, mainly within the alveoli,
      while endobronchial administration primarily targeted bronchial epithelium. Our
      results show that intravenously administered G9 dendrimer is an effective vector
      for pulmonary gene transfer and that transgene expression can be prolonged by
      repeated administration of dendrimer-complexed DNA.

PMID- 10910137
TI  - A novel telomerase-specific gene therapy: gene transfer of caspase-8 utilizing
      the human telomerase catalytic subunit gene promoter.
AB  - Apoptosis is a genetically encoded cell death process and is a pathway that may
      be disrupted in tumor cells. Therefore, therapies that restore the ability to
      undergo apoptosis are promising for the treatment of tumor cells. We have
      demonstrated that the transfer of apoptosis-inducible genes inhibits the growth
      of tumors in vitro and in vivo through induction of apoptosis. However, to
      restrict induction of apoptosis to tumor cells, we need to explore a tumor
      specific expression system of these genes. In the present study, we developed the
      telomerase-specific transfer system of apoptosis-inducible genes, utilizing the
      promoter of the human telomerase catalytic subunit (hTERT) gene. Approximately
      90% of tumors have telomerase activity whereas most normal cells do not express
      the activity. These observations indicate that telomerase is a particularly
      attractive target for the tumor-specific expression system of vectors. We
      demonstrate here that by using the hTERT promoter-driven caspase-8 expression
      vector (hTERT/caspase-8), apoptosis is restricted to telomerase-positive tumor
      cells of wide range, and is not seen in normal fibroblast cells without
      telomerase activity. Furthermore, treatment of subcutaneous tumors in nude mice
      with the hTERT/caspase-8 construct inhibited tumor growth significantly because
      of induction of apoptosis (p < 0.01). The telomerase-specific expression of
      apoptosis-inducible genes afforded by the hTERT promoter, therefore, may be a
      novel and promising targeting approach for the treatment of tumors with
      telomerase activity.

PMID- 10910138
TI  - Immunotherapy of a viral disease by in vivo production of therapeutic monoclonal
      antibodies.
AB  - Continuous and sustained in vivo production of monoclonal antibodies by
      engineered cells might render long-term antibody-based treatments cost-effective,
      avoid side effects associated with infusion of massive doses of antibody, and
      circumvent possible antiidiotypic responses against the therapeutic agent. The
      FrCasE retrovirus induces a lethal neurodegeneration on infection of newborn
      mice. We report here that implantation of cellulose sulfate capsules containing
      cells secreting an ectopic monoclonal antibody neutralizing FrCasE can prevent
      animals from developing the disease. All treated mice showed reduced or
      undetectable viremia in addition to a lack of the histopathological lesions
      characteristic of FrCasE infection. This work paves the way for a novel gene/cell
      antibody-based immunotherapy of a variety of severe viral and nonviral diseases.

PMID- 10910139
TI  - Targeted macrophage cytotoxicity using a nonreplicative live vector expressing a
      tumor-specific single-chain variable region fragment.
AB  - Antigen-specific recognition and subsequent destruction of tumor cells is the
      goal of vaccine-based immunotherapy of cancer. Often, however, tumor antigen
      specific cytotoxic T lymphocytes (CTLs) are either not available or in a state of
      anergy. In addition, MHCI expression on tumor cells is often downregulated.
      Either or both of these situations can allow tumor growth to proceed unchecked by
      CTL control. We have shown previously that tumor antigen-specific monoclonal
      antibodies can be expressed in vaccinia virus and that activated macrophages
      infected with this virus acquire the ability to kill tumor cells expressing that
      antigen. Here we show that a membrane-anchored form of the scFv portion of the
      MUC1 tumor antigen-specific monoclonal antibody, SM3, can be expressed on
      activated macrophages with the highly attenuated poxvirus, modified vaccinia
      Ankara (MVA), as a gene transfer vector. Cells infected with the MVA-scFv
      construct were shown to express the membrane-bound scFv by Western blot and FACS
      analysis. That cells expressing the membrane-anchored scFv specifically bind
      antigen was shown by FACS and by BIAcore analysis. GM-CSF-activated macrophages
      were infected with the construct and shown to recognize specifically MUC1
      expressing tumor cells as measured by IL-12 release. Furthermore, activated
      macrophages expressing the membrane-bound scFv specifically lyse target cells
      expressing the MUC1 antigen but not cells that do not express MUC1.

PMID- 10910140
TI  - Helper virus-free herpes simplex virus type 1 amplicon vectors for granulocyte
      macrophage colony-stimulating factor-enhanced vaccination therapy for
      experimental glioma.
AB  - Subcutaneous vaccination therapy with glioma cells, which are retrovirally
      transduced to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF),
      has previously proven effective in C57BL/6 mice harboring intracerebral GL261
      gliomas. However, clinical ex vivo gene therapy for human gliomas would be
      difficult, as transgene delivery via retroviral vectors occurs only in dividing
      cells and ex vivo glioma cells have a low growth fraction. To circumvent this
      problem, a helper virus-free herpes simplex virus type 1 (HSV-1) amplicon vector
      was used. When primary cultures of human glioblastoma cells were infected with
      HSV-1 amplicon vectors at an MOI of 1, more than 90% of both dividing and
      nondividing cells were transduced. When cells were infected with an amplicon
      vector, HSVGM, bearing the GM-CSF cDNA in the presence of Polybrene, GM-CSF
      secretion into the medium during the first 24 hr after infection was 1026
      ng/10(6) cells, whereas mock-infected cells did not secrete detectable GM-CSF.
      Subcutaneous vaccination of C57BL/6 mice with 5 x 10(5) irradiated HSVGM
      transduced GL261 cells 7 days prior to intracerebral implantation of 10(6) wild
      type GL261 cells yielded 60% long-term survivors (>80 days), similar to the 50%
      long-term survivors obtained by vaccination with retrovirally GM-CSF-transduced
      GL261 cells. In contrast, animals vaccinated with the same number of nontranduced
      GL261 cells or with GL261 cells infected with helper virus-free packaged HSV-1
      amplicon vectors carrying no transgene showed only 10% long-term survivors. In
      conclusion, helper virus-free HSV-1 amplicon vectors appear to be effective for
      cytokine-enhanced vaccination therapy of glioma, with the advantages that both
      dividing and nondividing tumor cells can be infected, no viral proteins are
      expressed, and these vectors are safe and compatible with clinical use.

PMID- 10910141
TI  - Analysis of 4070A envelope levels in retroviral preparations and effect on target
      cell transduction efficiency.
AB  - A number of stable producer cell lines for high-titer Mo-MuLV vectors have been
      constructed. Development has previously centered on increasing end-point titers
      by producing maximal levels of Mo-MuLV Gag/Pol, envelope glycoproteins, and
      retroviral RNA genomes. We describe the production yields and transduction
      efficiency characteristics of two Mo-MuLV packaging cell lines, FLYA13 and
      TEFLYA. Although they both produce 4070A-pseudotyped retroviral vectors
      reproducibly at >1 x 10(6) LFU ml(-1), the transduction efficiency of
      unconcentrated and concentrated virus from FLYA13 lines is poor compared with
      vector preparations from TEFLYA lines. A powerful inhibitor of retroviral
      transduction is secreted by FLYA13 packaging cells. We show that the inhibitory
      factor does not affect transduction of target cells by RD114-pseudotyped vectors.
      This suggests that the inhibitory factor functions at the level of envelope
      receptor interactions. Phosphate starvation of target cells shows a two-fold
      increase in Pit2 receptor mRNA and causes some improvement in FLYA13 virus
      transduction efficiency. Western blots show that FLYA13 viral samples contain an
      eight-fold higher ratio of 4070A envelope to p30gag than that of virus produced
      by TEFLYA producer cell lines. This study correlates overexpression of 4070A
      envelope glycoprotein in retroviral preparations with a reduction of transduction
      efficiency at high multiplicities of infection. We suggest that TEFLYA packaging
      cells express preferable levels of 4070A compared with FLYA13, which not only
      enables high-titer stocks to be generated, but also facilitates a high efficiency
      of transduction of target cells.

PMID- 10910143
TI  - Administration of neomycin resistance gene-marked EBV-specific cytotoxic T
      lymphocytes as therapy for patients receiving a bone marrow transplant for
      relapsed EBV-positive Hodgkin disease.

PMID- 10910142
TI  - A phase I-II trial to examine the toxicity of CMV- and EBV-specific cytotoxic T
      lymphocytes when used for prophylaxis against EBV and CMV disease in recipients
      of CD34-selected/T cell-depleted stem cell transplants.
AB  - Epstein-Barr virus (EBV)-induced lymphoproliferative disease and cytomegalovirus
      (CMV) infection are major causes of morbidity and mortality in individuals with
      compromised cellular immunity. Although anti-viral pharmacological agents exist,
      severe side effects such as myelosuppression often limit the application of these
      medications. Infusion of ex vivo-expanded, virus-specific cytotoxic T-lymphocytes
      (CTL) has been proven to be safe and efficacious for the prophylaxis and
      treatment of EBV and CMV complications. While EBV-specific CTL can be readily and
      reliably produced with EBV-immortalized B-lymphoblastoid cell lines (BLCL) as
      stimulators, current protocols for CMV-specific CTL, which use CMV-infected
      fibroblasts as stimulators, may be associated with alloreactivity and the need
      for cloning, as well as the potential for exposure to human blood-born infectious
      agents. Our laboratory has developed a novel system to generate EBV/CMV-bi
      specific CTL by co-culturing PBMC with autologous BLCL expressing a CMV protein
      pp65 (BLCLpp65) (Sun et al., 1999). pp65, an immunodominant CMV antigen, is
      transduced into BLCL by a recombinant retrovirus MSCVpp65. While low in
      alloreactivity, BLCLpp65-stimulated CTL are cytolytic to autologous cells
      infected with EBV or CMV, and this cytotoxicity is mediated by polyclonal, CD8+,
      MHC Class I-restricted T-cells. Further experiments revealed that retroviral
      transduction and expression of pp65 do not compromise the capacity of presenting
      EBV antigens, and T cells stimulated by BLCLpp65 recognize clinical strains of
      CMV (Sun et al., 2000). These data indicated that BLCLpp65 could substitute for
      BLCL as antigen presenting cells in adoptive immunotherapy against EBV-LPD, with
      the benefit of providing protection against CMV reactivation. This protocol is a
      Phase I/II study to examine the toxicity associated with and the immunologic
      effects of ex vivo simultaneously expanded EBV- and CMV-specific CTL for
      prophylaxis against EBV and CMV complications in recipients of CD34 selected/T
      cell depleted stem cell transplants (SCT). EBV/CMV-specific CTL will be generated
      from peripheral blood mononuclear cells (PBMC) of EBV/CMV-seropositive donors in
      a course of from 21-28 days by weekly stimulation with autologous BLCLpp65.
      Qualified CTL will be administered to consenting patients at 40, 60, and 80 days
      post-transpOFF criteria of molecular virology and immunological reconstitution,
      which include blood levels of pp65 antigen and EBV viral DNA, and virus-specific
      CTL precursor frequency. Patients will also be tested for replication-competent
      retrovirus at 3, 6, and 12 month intervals post-transplant to ensure bio-safety.

PMID- 10910144
TI  - Phase I study of chemokine and cytokine gene-modified autologous neuroblastoma
      cells for treatment of relapsed/refractory neuroblastoma using an adenoviral
      vector.

PMID- 10910145
TI  - Historical perspective on prostate brachytherapy.
AB  - Brachytherapy--radiation delivered close to or within a tumor--had its origins at
      the beginning of this century. Its use in prostate cancer was delayed first by
      the view that this was a relatively radioresistant cancer and then by clinical
      experience showing high failure and morbidity rates. More recently, technological
      innovations such as ultrasonography and computer-based treatment planning have
      made prostate brachytherapy a reasonable treatment option for many patients.

PMID- 10910146
TI  - Role of brachytherapy in patients with stage T1c, T2a adenocarcinoma of the
      prostate.
AB  - The precise role of brachytherapy in treating patients with adenocarcinoma of the
      prostate remains unclear. Recent literature suggests that the long-term disease
      free survival of patients with well-differentiated and localized tumors who
      receive brachytherapy is comparable to that of patients with similar tumors who
      are treated with radical prostatectomy or external-beam radiation. Advances in
      imaging technology, treatment planning software, and delivery apparatus have
      resulted in a technique that is accurate and reproducible. We explore the
      development of contemporary brachytherapy and examine the current published data
      relating to its emergence as a medically successful, cost-effective, and low
      morbidity therapeutic modality for patients with stage T(1c), T(2a) prostate
      cancer.

PMID- 10910147
TI  - Radical prostatectomy versus brachytherapy for early-stage prostate cancer.
AB  - BACKGROUND AND PURPOSE: The considerations in choosing a treatment for prostate
      cancer are potential for cure, acute toxicity, long-term morbidity, quality of
      life, and direct and indirect costs. The classic options are radical
      prostatectomy, external-beam radiation, and watchful waiting. During the last
      decade, technological advances have fostered another: brachytherapy. METHODS:
      This article compares brachytherapy and radical prostatectomy in terms of cancer
      control, complications, and cost using series from medical centers that have
      pioneered and advocated particular procedures. RESULTS: In the surgical series
      from Johns Hopkins, the 7-year success rate (no PSA >0.2 ng/mL) of anatomic
      radical prostatectomy was 97.8% in patients with stage T(2c) or lower disease and
      a Gleason score of < or =6. In the brachytherapy series from Seattle, the 7-year
      success rate (PSA < or =0.5 ng/mL) was 79%. Postoperatively, 68% of the patients
      who were potent preoperatively maintained erectile function, and 92% were fully
      continent. Urethral toxicity is slightly more common in patients treated by
      brachytherapy, but in the authors' series, no patient remained incontinent after
      6 months. Some patients became impotent during follow-up. The cost of
      brachytherapy ($16,200) is less than that of ($27,000), although the difference
      may be reduced by the use of neoadjuvant hormonal therapy with the former.
      CONCLUSION: Patients receiving brachytherapy appear to have a slightly higher
      rate of disease progression. The side effects generally are acceptable and may be
      less severe than those of surgery. Further follow-up data are needed to define
      the roles of these two treatments for early-stage prostate cancer.

PMID- 10910148
TI  - Role of transrectal ultrasonography in prostate brachytherapy.
AB  - Modern brachytherapy has been made possible by advances in ultrasound technology.
      This technology allows accurate determination of gland size, determination of the
      relation to the pubic arch, and real-time placement of the radioactive sources. A
      thorough familiarity with transrectal ultrasonography thus is required to produce
      high-quality implants consistently.

PMID- 10910149
TI  - Analysis of prostate seed loading for permanent implants.
AB  - The goal of radioactive seed implantation in prostate cancer is to treat the
      tumor to the necessary dose while minimizing the dose to adjacent normal
      structures. The uniform and peripheral loading schemes used in the past have
      serious limitations. However, with the availability of three-dimensional
      treatment-planning systems, it has become possible to do custom volume loading
      based on volumetric ultrasound imaging of the gland. As a result, the dose
      distributions are more uniform, and the doses to the urethra and rectum are
      maintained in a safe range.

PMID- 10910151
TI  - Treatment of high-grade low-stage prostate cancer by high-dose-rate
      brachytherapy.
AB  - BACKGROUND AND PURPOSE: The best management of patients with low-stage, high
      grade prostate cancer remains unclear. In an attempt to improve the outcomes of
      this high-risk group, we have offered those with Gleason > or =7 cancers
      removable-source high-dose-rate (HDR) brachytherapy in combination with external
      beam radiation. PATIENTS AND METHODS: We reviewed the clinical histories of 61
      consecutive patients with high-grade clinical stage T1-T2 lesions who received
      the combination radiation therapy between March 1997 and November 1998. The
      average Gleason score was 7.5. The HDR brachytherapy was given in three sessions
      with removable-source afterloaded (192)Ir to a minimum peripheral dose of 6 Gy.
      Conformal external-beam radiation in 25 fractions to a dose of 50 Gy was given
      beginning 1 week later. Patients with prostate volumes >40 cc received a
      luteinizing hormone-releasing hormone analog before brachytherapy. RESULTS: Among
      the 52 patients available for follow-up (average duration 11.8 months), there has
      been one death from prostate cancer. After treatment, only one patient had an
      initial rise in serum prostate specific antigen (PSA) concentration. In addition
      to the patient who died, there have been three confirmed treatment failures.
      Toxicity was mild, with only two patients having RTOG grade 3 or 4 effects.
      Neither of them required surgery. CONCLUSION: Although long-term results are not
      available, available data suggest that HDR brachytherapy plus external-beam
      radiation is at least as effective as any single therapy for high-risk, low-stage
      prostate cancer. The toxicity is acceptable.

PMID- 10910150
TI  - Minimally invasive treatment for localized adenocarcinoma of the prostate: review
      of 1048 patients treated with ultrasound-guided palladium-103 brachytherapy.
AB  - PURPOSE: To assess the effectiveness of palladium-103 brachytherapy in stage T1
      and T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The charts of 1048
      patients treated between 1991 and 1999 with transperineal realtime ultrasound
      guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum
      prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients,
      780 had sufficient data for this report. Preoperative total androgen blockade
      (leuprolide and flutamide) was used selectively in patients whose prostate size
      was >50 cc and those whose tumors had a Gleason score of >7. RESULTS: At 1 year,
      86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5
      years, 86% of the 166 patients with data available had stable PSA values <1.5
      ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients
      with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated
      with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those
      treated with radioisotope monotherapy. There was one disease-related death; the
      principal morbidity was short-term bladder and bowel irritation without permanent
      sequelae. Impotence occurred in approximately 15% of patients, and incontinence
      occurred in 5% of those who had undergone prior transurethral resection of the
      prostate. CONCLUSION: The technique used in this study proved effective in
      reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1
      and 2 years postoperatively. These results are comparable to those of external
      beam radiation therapy and radical prostatectomy while demonstrating a
      significant reduction in morbidity.

PMID- 10910152
TI  - High- and low-risk prostate cancer treated with 3D CT-guided brachytherapy: 1-to
      5-year follow-up.
AB  - PURPOSE: To provide a preliminary report of 301 patients treated for prostate
      carcinoma with three-dimensional CT-guided transischiorectal stereotactic
      brachytherapy using either iodine-125 or palladium-103 seeds as monotherapy.
      PATIENTS AND METHODS: Patients with clinical stage T1, T(2ab), or T(3ab) disease
      with prostate volumes 23 to 180 cm3 and serum prostate specific antigen (PSA)
      concentrations of 0.9 to 143 ng/mL had seeds placed 10 mm apart under CT
      guidance. No androgen blockade was used postoperatively, but 47% of the patients
      had hormonal therapy preoperatively. RESULTS: At 12 to 63 months (median 26
      months) of follow-up, PSA concentrations had decreased to <2 ng/mL in 90% of the
      patients and to <1 ng/mL in 83%. Four patients underwent transurethral resection
      or incision at least 12 months after implantation; none became incontinent. Three
      patients had rectal ulceration that lasted for several months. CONCLUSIONS:
      Computed tomography-guided transischiorectal brachytherapy allows accurate
      placement of radionuclide seeds in prostate glands of all sizes. The early
      results, as judged by serum PSA, are encouraging.

PMID- 10910153
TI  - Real-time magnetic resonance imaging-guided brachytherapy in the treatment of
      selected patients with clinically localized prostate cancer.
AB  - BACKGROUND AND PURPOSE: A real-time three-dimensional magnetic resonance imaging
      (MRI)-guided implant technique has been designed and implemented. This report
      summarizes the dosimetry achieved and the acute morbidity in the first patients.
      PATIENTS AND METHODS: To date, 43 patients with clinical stage T(1c)N(X)M(0)
      prostate cancer, serum prostate specific antigen <10 ng/mL, and biopsy Gleason
      score no higher than 3 + 4 have been treated. The procedure was performed using
      an open magnet, with axial T1-weighted and fast spin echo images. The prescribed
      minimum radiation dose to the peripheral zone was 160 Gy. The total activity
      implanted ranged from 18.8 to 47.5 mCi using 43 to 120 (median 80) (125)I seeds.
      Dosimetric analyses were performed intraoperatively in real time for the tumor,
      anterior rectal wall, and prostatic urethra. RESULTS: The percent of the clinical
      target volume receiving the prescription dose was 89% to 99% (median 96%). Using
      a conservative estimate of 164 Gy, no more than 9% of the urethral volume
      exceeded the tolerated dose. Using an estimated tolerated dose of 82 Gy, 30% to
      100% (median 68%) of the anterior rectal wall volume was within the dose limit.
      Thirty-nine patients voided spontaneously within 3 hours of Foley catheter
      discontinuation, although four patients required recatheterization for a period.
      No patient reported gastrointestinal or sexual dysfunction during the first
      postoperative month. CONCLUSION: A real-time MR-guided technique can achieve a
      minimum of 89% coverage of the tumor volume while maintaining the prostatic
      urethra and most of the anterior rectal wall below tolerance levels. Acute
      morbidity was minimal. Further follow-up is needed to ascertain the impact on
      cancer control and quality of life.

PMID- 10910154
TI  - Health-related quality of life and morbidity in patients receiving brachytherapy
      for clinically localized prostate cancer.
AB  - Health-related quality of life must be a factor when treatment options are
      discussed with a patient. Quality of life is measured by validated questionnaires
      that include generic and disease-targeted measures. Urinary and rectal symptoms
      and sexual function are evaluated after treatment for prostate cancer. Quality of
      life is adversely affected in the early post-brachytherapy period primarily by
      the urinary morbidity. Urinary symptoms peak 2 months after treatment and decline
      thereafter, although severe long-term urinary toxicity occurs in 3% to 12% of
      patients. Urinary symptoms are generally treated with alpha-blocker and
      anticholinergic drugs, but 2% to 5% of patients require transurethral resection
      of the prostate to relieve persistent obstruction. However, 6 months after
      treatment, overall satisfaction is excellent, and the majority of patients would
      recommend the procedure to a friend.

PMID- 10910155
TI  - Biopsy results after real-time ultrasound-guided transperineal implants for stage
      T1-T2 prostate cancer.
AB  - PURPOSE: To analyze the results of ultrasound-guided brachytherapy for stage T1
      T2 prostate cancer, as shown by biopsy results. PATIENTS AND METHODS: The 268
      patients (mean age 66 years; range 41-83 years) underwent real-time ultrasound
      guided implantation of either iodine-125 (N = 186) or palladium-103 (N = 82)
      seeds. Of these patients, 96 (36%) received total androgen suppression for 3
      months prior to and 3 months after implantation. Prostate biopsy was performed 24
      months later, with the six to eight cores all being interpreted by the same
      pathologist. Each specimen was rated either positive or negative for cancer.
      RESULTS: Of the 268 patients, 238 (89%) had a negative biopsy at 24 months. Among
      the patients receiving androgen suppression, 2% were found to have positive
      biopsies compared with 16% of those not given hormones (P = 0.004). Of the 155
      patients with stage T1-T(2a) cancer, 6% had a positive biopsy compared with 19%
      of patients with stage T(2b) or T(2c) cancer (P = 0.001). In the entire series,
      the pretreatment serum concentration of prostate specific antigen, Gleason score,
      and isotope (I v Pd) were not significant predictors of a positive biopsy.
      However, among the 172 patients who did not receive androgen suppression, all
      three factors were predictive: 42% for Gleason score of 7 to 10 v 13% for Gleason
      score < or =6 (P = 0.001): 25% for pretreatment PSA concentration >10 ng/mL v 13%
      for PSA < or = 10 ng/mL (P = 0.05); and 27% for stage T(2b) or T(2c) v 9% for
      stage T1 or T(2a) (P = 0.001). The isotope used and the last PSA value were not
      significant predictors. CONCLUSION: Brachytherapy provides excellent local
      control of prostate cancer, with 89% of patients having negative biopsies 2 years
      after treatment. High-risk patients may benefit from the addition of androgen
      suppression.

PMID- 10910156
TI  - Minimizing rectal and urinary complications in prostate brachytherapy.
AB  - With any therapy for early prostate cancer, control must be evaluated with a view
      to toxicities. Brachytherapy may be associated with urethral and rectal toxicity
      and erectile impotence. Patients with large glands or significant symptoms before
      treatment are at greatest risk. Long-term toxicity can be minimized by
      understanding the tolerance of the normal tissues and meticulous placement of the
      radioactive seeds.

PMID- 10910157
TI  - Salvage radical prostatectomy after radiation therapy and brachytherapy.
AB  - Local recurrence after any type of radiation therapy presents the clinician with
      a significant challenge. If there is no evidence of metastatic disease, patients
      can be offered a potentially curative salvage prostatectomy. To qualify for such
      surgery, patients should be at least 12 months from the completion of radiation
      and have at least a 10-year life expectancy; ideally, they will have a serum
      prostate specific antigen concentration <10 ng/mL and a Gleason score of 7 or
      less. Perioperative complications are substantial, with urinary incontinence
      rates of 40% to 50% and rectal injury rates of 10% to 15%. Long-term disease-free
      survival rates of 30% to 40% can be expected.

PMID- 10910158
TI  - Propagation of spontaneous synchronized activity in cortical slice cultures
      recorded by planar electrode arrays.
AB  - The spatial propagation of synchronized activity in cortical slice cultures was
      characterized by multi-site extracellular recording. Spontaneous activity was
      studied in normal culture medium, and in bicuculline- or kainic acid-containing
      media. A common feature in all these conditions was that activity was generated
      first in superficial layers (i.e., layer I/II) before spreading over the whole
      area of the slice. In culture medium or bicuculline-containing medium, the
      initiation site of the activity was not constant and showed a large variety of
      patterns of horizontal propagation. Kainic acid induced epileptiform activity,
      consisting of intense initial bursts followed by repetitive after-discharges.
      Though the patterns of spatial propagation of the bursts were variable as in the
      other conditions, the after-discharges followed a constant path. Cross
      correlation analysis indicated that the network moved in a graded fashion to a
      steady state during the sequence of after-discharges.

PMID- 10910159
TI  - Power frequency magnetic field exposure and gap junctional communication in Clone
      9 cells.
AB  - Exposure to a power-frequency magnetic field has been reported to produce a
      statistically significant inhibition of gap junctional communication (GJC) in
      Clone 9 cells that have been pre-stressed by treatment with low concentrations of
      chloral hydrate (CH) [C.F. Blackman, J.P. Blanchard, S.G. Benane, D.E. House,
      J.A. Elder, Double blind test of magnetic field effects on neurite outgrowth,
      Bioelectromagnetics, 19 (1998) 204-209]. This observation might provide
      mechanistic insight into the possible role of electromagnetic fields (EMFs) in
      the carcinogenic process, since cancer cells frequently show decreased or absent
      GJC, and tumor promoting chemicals have been observed to inhibit GJC. Magnetic
      field exposure conditions were 45 Hz, 23.8 microT rms + parallel DC 36.6 microT,
      for 30 min of exposure. The responses of Clone 9 cells to the GJC-inhibiting
      effects of the tumor promoter 12-O-tetradecanoylphorbol 13-acetate and the
      chemical CH were evaluated and compared to reported results [S.G. Benane, C.F.
      Blackman, D.E. House, Effects of perchloroethylene and its metabolites on
      intercellular communication in Clone 9 rat liver cells, J. Toxicol. Environ.
      Health, 48 (1996) 427-437]. Before magnetic field exposure, cells were exposed
      for 24 h to either 3 (nine experiments) or 5 mM (11 experiments) CH to produce
      GJC of 67% or 50%, respectively, relative to unexposed controls. GJC was assessed
      microscopically using the scrape-loading technique and a blinded protocol. No
      statistically significant effect was observed due to magnetic field exposure with
      either CH concentration.

PMID- 10910160
TI  - Perspectives for microelectrode arrays for biosensing and membrane
      electroporation.
AB  - Electrochemical microelectrode devices are among the great challenges for
      bioelectrochemistry, cell biology and recently also for biomedical research and
      new clinical electrotherapies. Two representative cases in cell biology and
      medical research for new trends in the technical devices are selected, heading at
      new diagnostic and therapeutic clinical applications. One example is from the
      field of biosensing cholinergic neurotransmitter substances by the nicotinic
      acetylcholine receptor (AcChoR) in solid-supported lipid bilayer membrane and the
      other one refers to new developments of electrode systems for the electrochemical
      delivery of drugs and genes to biological cell aggregates and tissue by the
      powerful method of membrane electroporation. In both cases addressed to, the new
      developments include the use of electrical feedback control of electrode arrays
      for biosensing processes as well as for the extent and duration of tissue
      electroporation. In line with the impressive advances in medical microsurgery,
      where increasingly smaller organ targets become accessible, microelectrode
      systems have become a continuous technical challenge for bioanalytical purposes
      and, as discussed here in some detail, for the new field of the electroporative
      delivery of effector substances like drugs and genes, using miniaturized
      electrochemical electrode arrays.

PMID- 10910161
TI  - Theoretical modeling of the effects of shock duration, frequency, and strength on
      the degree of electroporation.
AB  - Electroporation is becoming an increasingly important tool for introducing
      biologically active compounds into living cells, yet the effectiveness of this
      technique can be low, particularly in vivo. One way to improve the success rate
      is to optimize the shock protocols, but experimental studies are costly, time
      consuming, and yield only an indirect measurement of pore creation.
      Alternatively, this study models electroporation in two geometries, a space
      clamped membrane and a single cell, and investigates the effects of pulse
      duration, frequency, shape, and strength. The creation of pores is described by a
      first order differential equation derived from the Smoluchowski equation. Both
      the membrane and the cell are exposed to monophasic and biphasic shocks of
      varying duration (membrane, 10 micros-100 s; cell, 0.1 micros-200 ms) and to
      trains of monophasic and biphasic pulses of varying frequency (membrane, 50 Hz-4
      kHz; cell, 200 kHz-6 MHz). The effectiveness of each shock is measured by the
      fractional pore area (FPA). The results indicate that FPA is sensitive to shock
      duration only in a very narrow range (membrane, approximately 1 ms; cell,
      approximately 0.25 micros). In contrast, FPA is sensitive to shock strength and
      frequency of the pulse train, increasing linearly with shock strength and
      decreasing slowly with frequency. In all cases, monophasic shocks were at least
      as effective as biphasic shocks, implying that varying the strength and frequency
      of a monophasic pulse train is the most effective way to control the creation of
      pores.

PMID- 10910162
TI  - Electrochemical properties of Doyle catalyst immobilized on carbon paste in the
      presence of DNA.
AB  - The electrochemical behaviour of Doyle catalyst, dirhodium(II) tetrakis [methyl-2
      oxopyrrolidine-5(S)-carboxylate] (Rh2(5S-MEPY)4), immobilised in graphite powder
      was evaluated preparing the carbon paste electrode, as well as its
      electrochemical properties in the presence (DCDE) and absence (DCE) of DNA. In
      both cases, one redox couple at 0.35 V vs. SCE in 0.5 mol l(-1) KCl solution at
      pH 7 and 10 mV s(-1) was observed. The resolution of the peak current in the
      voltammetric studies and other electrochemical properties were improved when the
      Doyle catalyst was immobilised in the presence of DNA. The estimated rate
      constants were of 17 and 26 s(-1) for a scan rate of 1 V s(-1) for DCE and DCDE,
      respectively. Furthermore, the interaction between rhodium carboxylates and
      electrolytes become more evident, suggesting a good hydrophilic and conductor
      character of this biopolymer.

PMID- 10910163
TI  - Redox potential is a determinant in the Escherichia coli anaerobic fermentative
      growth and survival: effects of impermeable oxidant.
AB  - Decrease of redox potential (Eh) down to -550-600 mV in the Escherichia coli
      culture is observed during growth in either anaerobic or aerobic conditions. The
      E. coli growth and survival under anaerobic fermentative conditions were found to
      be strongly inhibited by potassium ferricyanide in the concentration of 1 mM,
      when Eh was decreased to -50-100 mV. This oxidant also resulted in approximately
      2-fold decrease of total and N,N'-dicyclohexylcarbodiimide (DCCD)-inhibited H+
      efflux, 2.5-fold inhibition in K+ influx, 1.5-fold less K+ accumulation, and
      delayed a decrease in Eh to negative values by bacteria. K3[Fe(CN)6] was shown to
      block an ATP-dependent increase in the amount of accessible thiol groups of
      membrane vesicles that was inhibited by DCCD, and this inhibition by the oxidant
      could be recovered by dithiothreitol. These effects were not observed with cells
      growing under aerobic conditions. The effects of K3[Fe(CN)6], an impermeable
      oxidant, might be explained by the fact that redox potential is a determinant in
      the E. coli anaerobic fermentative growth and survival that has a regulatory role
      in maintaining H+ and K fluxes and the number of accessible thiol groups on
      membrane.

PMID- 10910164
TI  - Non-thermal effects of continuous 2.45 GHz microwaves on Fas-induced apoptosis in
      human Jurkat T-cell line.
AB  - Non-thermal effects of microwaves (MWs) are one of the main issues studied for
      revising standards. The effects of MW exposure on apoptosis at non-thermal level
      (48 h, 2.45 GHz, 5 mW/cm2) have been studied. Results obtained assess non-thermal
      MW effects on Fas, but neither on butyrate- nor on ceramide-induced apoptosis in
      human Jurkat T-cell line. These data show that MW interacts either with Fas
      pathway between receptor and caspase-3 activation or on membrane proteins (i.e.
      Fas receptor or neurosphyngomyelinase).

PMID- 10910165
TI  - Oxidative modification of neurogranin by nitric oxide: an amperometric study.
AB  - Neurogranin (Ng) is a neuron-specific protein kinase C (PKC) substrate, which
      contains four cysteine (Cys) residues. Recently, it has been shown that Ng is a
      redox-sensitive protein and is a likely target of nitric oxide (NO) and other
      oxidants [F.-S. Sheu, C.W. Mahoney, K. Seki, K.-P. Huang, Nitric oxide
      modification of rat brain neurogranin affects its phosphorylation by protein
      kinase C and affinity for calmodulin, J. Biol. Chem. 271 (1996) 22407-22413: J.
      Li, J.H. Pak, F.L. Huang, K.-P. Huang, N-methyl-D-aspartate induces
      neurogranin/RC3 oxidation in rat brain slices, J. Biol. Chem. 274 (1999) 1294
      1300]. In this study, we directly examine the redox reactions between dissolved
      NO and Cys as well as between NO and bacterial expressed Ng in its reduced form,
      at concentrations approximate to the physiological levels in phosphate buffer
      solution (PBS) under aerobic conditions. The reaction kinetics are measured
      directly by our newly developed electrochemical sensor. Our sensor is based on
      the chemical modification of electrode with immobilized nanoparticles of
      transition metal palladium (Pd) which serves as catalytic centers for the
      electrochemical oxidation of thiol and NO selectively and quantitatively at
      different potentials. It detects Cys and Ng in a linear range from nano to
      micromolar concentration at + 450 mV, vs. a saturated calomel reference electrode
      (SCE), while the detection of NO at the sensor can be optimally achieved at + 700
      mV (vs. SCE) with a linear current-to-concentration range of nM to microM. It
      thus provides a selective control to monitor two reactants independently. With
      this sensor as a detector, we found that (1) the oxidation of either Cys or Ng by
      NO is a fast reaction which reaches a near completion within 1-2 min at its
      physiological concentration; and (2) after the completion of reaction, NO is
      mostly, if not all, regenerated, an observation consistent with the reaction
      mechanism involving the formation of S-nitrosothiol as an intermediate. The
      reaction kinetics of both NO to Cys and NO to Ng implies that NO can achieve
      local action on cellular proteins in addition to its effect on targets located in
      neighboring cells via concentration-gradient-dependent diffusion.

PMID- 10910166
TI  - Redox characteristics of manganese and cobalt complexes obtained from pyridine N
      oxide.
AB  - Manganese and cobalt complexes, using pyridine N-oxide as ligand, have been
      synthesized, and their cyclic and square-wave voltammetric measurements have been
      carried out. The results reveal that the complexes exhibit different voltammetric
      pattern, which suggests that the redox processes are most probably metal
      centered. In both complexes, extra redox activity is observed once the potential
      exceeds certain value of the voltage. The observation of an oxidation wave in
      manganese complex at + 0.75 V vs. Ag/AgCl or + 0.95 V vs. NHE strongly suggests
      that this complex can bring about oxidation of water and can, thus, serve as a
      synthetic analogue of water oxidizing complex (WOC) of PS II.

PMID- 10910167
TI  - Electrocatalytic oxidation of NADH at the self-assembled monolayer of nickel(II)
      macrocycle on gold electrode.
AB  - Electroactive self-assembled monolayers (SAMs) of macrocyclic Ni(II) complex (1)
      were fabricated on gold electrode and its electrochemistry has been studied in
      different supporting electrolytes. Substantial stabilization of tervalent nickel
      and a significant negative shift of formal potential of the Ni(3+/2+) couple have
      been observed when the supporting electrolyte is changed from nitrate to
      phosphate. Coordination of supporting electrolyte anion with the Ni(III) complex
      shifts the formal potential and thus tervalent nickel is stabilized. SAM of 1
      electrode shows an excellent electrocatalytic activity towards the oxidation of
      NADH in aqueous NaNO3 solution, whereas it scarcely catalyzes the oxidation of
      NADH in aqueous phosphate buffer solution. The electrocatalytic oxidation of NADH
      in Na2SO4 solution is less efficient than that in NaNO3 solution. The anion
      dependent electrocatalysis has been discussed on the basis of the difference in
      the coordinating ability of the anions with the tervalent nickel centers. Steady
      state current has been measured for the oxidation of NADH and it was proportional
      to the concentration of NADH.

PMID- 10910168
TI  - Photoelectric measurements of s-BLM/nucleoli: a new technique for studying
      apoptosis.
AB  - A new method based on photoelectric measurement for analyzing apoptosis of cell
      free MCF-7 nucleoli is reported. Supported bilayer lipid membrane (s-BLM) was
      used to enclose nucleoli in biological environment. The s-BLM was self-assembled
      on the wall of a super-thin cell. During the apoptosis induced by Taxol, the
      photoelectric current of the self-assembled s-BLM/nucleoli was found decreasing
      with time, suggesting the degradation of nucleus DNA. Electron transfer along the
      DNA double helix and along nuclear skeleton is assumed in the interpretation.
      This novel photoelectric analytical method may provide a rapid and sensitive
      technique to evaluate apoptosis.

PMID- 10910169
TI  - An electroanalytical investigation on the redox properties of lacidipine
      supporting its anti-oxidant effect.
AB  - The redox properties of lacidipine (PyH2), one of the most pharmacologically
      active N-unsubstituted 1,4-dihydropyridines, have been studied by cyclic
      voltammetry and controlled potential electrolysis in acetonitrile, an aprotic
      solvent that is, at best, a mimic of the lipofilic layer of biological membranes.
      PyH2 undergoes a two-electron oxidation process involving two consecutive one
      electron releases, the latter requiring potentials much less positive than the
      former. The overall process occurs through a primary one-electron step
      accompanied by a fast proton release, with the formation of a neutral radical
      (PyH*), which undergoes a further and quite easier one-electron step, thus
      providing the main ultimate product (PyH+) consisting in the protonated form of
      the parent pyridine derivative. This appears relevant for the anti-oxidant effect
      since the radical intermediate is much more prone to be oxidized than to be
      reduced, thus preventing the propagation of the oxidative chain reaction. The
      mentioned release of protons in the primary electrode step causes the overall
      process to be complicated by a parassite side reaction involving the coupling
      between one of the electrode products (H+) and the starting species. The
      protonation of PyH2 subtracts part of the original species from the electrode
      process because the parent cationic species (PyH3+) is no longer electroactive.
      This parassite reaction occurs rather slowly in the timescale of
      electroanalytical measurements (the relevant kinetic constant has been estimated
      to be 6.4 l mol(-1) s(-1)), thus markedly affecting the process only in the
      presence of relatively high PyH2 concentrations and progressively decreasing with
      the starting PyH2 concentration. All the products formed in the oxidation process
      (PyH+, H+ and PyH3+) have been identified by voltammetric evidences based on deep
      investigations on their cathodic behaviour. The advantageous anti-oxidant
      properties displayed by PyH2 with respect to those exhibited by phenolic anti
      oxidants such as vitamin E are also discussed.

PMID- 10910170
TI  - Electrochemical signaling in green plants: effects of 2,4-dinitrophenol on
      variation and action potentials in soybean.
AB  - Nerve cells in animals and phloem cells in plants share one fundamental property:
      they possess excitable membranes by which electrical excitations in the form of
      action potentials can propagate. Action potentials in green plants can be as fast
      as the action potentials in axons of nervous cells. The presence of the pesticide
      2,4-dinitrophenol (DNP) in soil is a most serious environmental problem and has
      an impact on agriculture and human health. In the present work we show that DNP
      induces fast action potentials and decreases the variation potential in a
      soybean. The speed of the propagation of action potentials is up to 2 m/s, and
      the duration time of single action potentials is typically 20 ms. The automatic
      measurement of the electrical potential difference can be effectively used in
      environmental plant physiology, as well as for studying molecular mechanisms of
      transport processes and the influence of external stimuli on plants.

PMID- 10910171
TI  - Are the stainless steel electrodes inert?
AB  - The electrodes used for electroporation, electrofusion, and electrotransfection,
      as well as in electrochemotherapy should not interact with the object and release
      electrolysis products. We studied how far the stainless steel electrodes fulfil
      these requirements. The results showed that in the case of the exponential
      electric pulses with amplitude of 3 kV cm(-1) and time constant of 0.5 ms, the
      stainless steel electrodes released ferrous ions to a concentration of several
      micromoles per liter. We determined experimentally the dependence of the amount
      of the released ferrous ions on the pulse parameters and on the ionic strength of
      the medium. It was shown that the released ferrous ions should not be ignored.
      They could be of importance for the bleomycin electrochemotherapy.

PMID- 10910172
TI  - Dosimetry bibliography.

PMID- 10910174
TI  - Scientific contributions of ankylosing spondylitis patient advocacy groups.
AB  - The Spondylitis Association of America has been the driving force behind a major
      research initiative in the US, having leveraged a substantial amount of money
      into a $4.5 million grant from the National Institute of Arthritis and
      Musculoskeletal and Skin Diseases. The grant last year established the North
      American Spondylitis Consortium to expedite the search for genes that determine
      susceptibility to ankylosing spondylitis. The German Ankylosing Spondylitis
      Society, which has more than 14,000 patient members, initiated in 1996 a
      professional survey of ankylosing spondylitis patients, with financial support
      from the German Federal Health Ministry. The results of this survey have recently
      been published, but only in the German language; a part of it is summarized here
      in English. Following are some of the important findings. The average age at
      disease onset does not differ significantly between men and women, but there is a
      significantly longer delay in disease diagnosis among female patients. The
      average delay in disease diagnosis is getting shorter; there was an average delay
      of 15 years for patients with disease onset in the 1950s, and it decreased to 7.5
      years for patients with disease onset between 1975 and 1979. There was a
      relatively greater degree of underdiagnosis of the disease among female than male
      patients in the past; whereas only 10% of the patients in whom the disease was
      diagnosed in about 1960 were women, this percentage has progressively increased
      in the subsequent decades to reach 46% among those in whom the disease was
      diagnosed since 1990. The speed at which spinal ankylosis progresses is slower in
      female patients, but women are in a significantly worse situation than men in
      terms of pain and the need for drug therapy, even though the women in the German
      Ankylosing Spondylitis Society sample are, on average, younger than the men and
      have a shorter average disease duration. It is possible that the slower and
      relatively incomplete progression to spinal ankylosis in female patients impedes
      the occurrence of a decrease in pain with time, compared with that observed in
      male patients.

PMID- 10910173
TI  - Update: the twenty subtypes of HLA-B27.
AB  - HLA-B27 is a serologic specificity that encompasses 20 different alleles-HLA
      B*2701 to B*2720. These alleles are also called subtypes of HLA-B27, and they
      have evolved from the B*2705 subtype, mostly from changes in exons 2 and 3 (which
      encode the alpha 1 and alpha 2 domains of the peptide binding groove,
      respectively). Occurrence of ankylosing spondylitis (AS) or related
      spondyloarthropathy (SpA) has thus far been documented in subjects possessing any
      one of the first 10 subtypes. However, B*2706 in Southeast Asian and B*2709 in
      the Italian island population of Sardinia may have a relatively much weaker
      association with AS. The 10 most recent subtypes have not yet been studied for
      disease association. There may exist a hierarchical ranking, resulting, in part,
      from differences in other co-inherited genetic factors, or due to environmental
      factors; eg, B*2705 is clearly disease-associated throughout the world, but not
      among the West Africans of Senegal and Gambia. It is important to investigate
      whether certain subtypes show any preferential association with some of the
      clinical features or forms of AS and related SpA among the various ethnic/racial
      populations and geographic regions of the world. This may help to identify the
      polymorphic positions of HLA-B27 that may have a disease-predisposing role.

PMID- 10910175
TI  - HLA-B27 and immunogenetics of spondyloarthropathies.
AB  - The arthritogenic peptide hypothesis has inspired research aimed at defining the
      peptide-presenting properties of HLA-B27 subtypes and their relation to
      ankylosing spondylitis. Various studies have shed new light on the influence of
      HLA-B27 polymorphism in modulating peptide binding and T-cell antigen
      presentation. Moreover, multiple factors along the antigen processing-loading
      pathway, including tapasin, contribute to shaping the HLA-B27 repertoire. Other
      studies have revealed significant peptide-binding similarities between HLA-B27
      and subtypes of HLA-B39, supporting a role of this antigen in
      spondyloarthropathy. A putative pathogenetic role of the HLA-B27 heavy chain,
      initially suggested from studies in transgenic mice, is claimed on the basis of
      novel, yet circumstantial, evidence concerning an apparently unusual capacity of
      the heavy chain to form stable homodimers or misfold after biosynthesis. Finally,
      it appears that arthritogenic infections might downregulate HLA-B27 expression,
      favoring bacterial survival. The specificity and mechanism of this phenomenon are
      yet to be defined.

PMID- 10910176
TI  - Chlamydia and associated arthritis.
AB  - An inflammatory arthritis is known to follow urogenital infection with the
      intracellular bacterium Chlamydia trachomatis in some individuals, and recent
      research results have elucidated important aspects of the characteristics of this
      Chlamydia-associated joint disease. Although the several extra-articular features
      of Chlamydia-induced arthritis have been defined clinically, their detailed
      causes remain largely unexplained. Current data indicate that the clinical
      characteristics of joint disease associated with C. trachomatis infection and
      those associated with postenteric arthritis are not easily distinguishable,
      although the response of each to antibiotic therapy does differ. The biologic
      characteristics of Chlamydia and enteric organisms in the joint show profound
      differences, and these are probably responsible for the variable responses to
      drug treatment. Molecular analyses of synovial C. trachomatis have demonstrated
      that long-term infection of the joint occurs primarily in synovial tissue and
      that the organism exhibits highly unusual biologic properties in its synovial
      context. These unusual molecular, biochemical, and other characteristics provide
      explanations for the frequent culture negativity of joint materials for C.
      trachomatis and for several other aspects of the arthritogenic process. Much
      remains to be learned concerning the behavior of this organism in the joint and
      concerning its interaction with its synovial host cells.

PMID- 10910177
TI  - Clinical aspects, outcome assessment, and management of ankylosing spondylitis
      and postenteric reactive arthritis.
AB  - The cause of ankylosing spondylitis remains unclear. Proof that this disorder is
      an autoimmune disease attributable to crossreactivity between bacteria and HLA
      B27 is still lacking. Differences in endogenous peptide presentation by HLA-B27
      subtypes might be relevant in the etiopathogenesis. Fractures of the osteoporotic
      spine contribute to morbidity. Spinal cord injury may occur. MR imaging enables
      identifying sacroiliitis earlier than plain radiography. Sweet syndrome has now
      been described in patients with ankylosing spondylitis and Crohn disease.
      Progress has been made in the assessment of ankylosing spondylitis. There are now
      core sets for different settings and validated instruments for functioning and
      disease activity that will enable demonstrating efficacy of new therapeutic
      interventions. The debate continues on classification of postinfectious and
      reactive arthritis. Bacterial antigens may be found in the inflamed joints;
      occasionally 16S ribosomal RNA is also demonstrated. Antibiotics seem not to be
      effective in postenteric reactive arthritis. More than 25 years have now elapsed
      since the association between ankylosing spondylitis and HLA-B27 was first
      described in 1973. The cause of this disease is still unknown, but a lot of
      progress has been made regarding the molecular structure of HLA-B27, the spectrum
      of disease, the clinical and radiographic assessment of ankylosing spondylitis,
      and its treatment. Recent advances in research on ankylosing spondylitis are
      reviewed here.

PMID- 10910178
TI  - Juvenile spondyloarthropathies.
AB  - This paper reviews the recent literature on the juvenile spondyloarthropathies.
      Several case reports emphasized clinical characteristics of the
      spondyloarthropathies including reactive arthritis. MR imaging seemed to enhance
      the detection of sacroiliitis in children with spondyloarthropathies. The
      presence of different cytokines in various forms of juvenile arthritis including
      the juvenile spondyloarthropathies was investigated and suggested a role for the
      anti-inflammatory cytokines in milder disease. Evidence for the association of
      low-molecular-weight polypeptide gene polymorphism with susceptibility to acute
      anterior uveitis was found in a Mexican population of patients with
      spondyloarthropathies, including 80 with juvenile spondyloarthropathy. A review
      of therapeutic use of sulfasalazine in children with chronic arthritis, including
      those with juvenile spondyloarthropathy, concluded that it was safe and
      effective. Last, a study assessed aerobic fitness and physical activity in
      patients with juvenile spondyloarthropathy in remission and suggested a decline
      in physical fitness in older patients.

PMID- 10910179
TI  - Psoriatic arthritis: evolving concepts.
AB  - Articles included in this review reflect the recent advances made in basic
      research and the clinical management of psoriatic arthritis in 1999. Some of
      these advances are destined to modify the current approach to the disease. The
      problems related to nosology and epidemiology, the two still controversial
      aspects, are discussed first. Genetic susceptibility to psoriasis and psoriatic
      arthritis, and the inciting role played by some bacteria, are confirmed, and
      attention is focused on the role of T cells, cytokines, adhesion molecules, and
      angiogenetic factors in the skin and synovial membrane. New classification
      criteria are provided and a simplified spectrum of the disease seems to emerge
      from clinical studies. Modern imaging techniques enable early articular changes
      to be discovered, support innovative pathogenetic hypotheses, and allow new
      therapeutic approaches.

PMID- 10910180
TI  - Spondyloarthropathies in sub-Saharan Africa.
AB  - HLA-B27 is virtually absent in most of the sub-Saharan Africa populations, and
      ankylosing spondylitis is rare; only a few patients have been reported from
      central and southern Africa. HLA-B27 was present in only one of 17 patients (6%).
      The disease shows clinical features that are similar to those observed in white
      HLA-B27-negative patients with ankylosing spondylitis; ie, the disease onset is
      later compared with HLAB27-positive patients, the patients rarely get acute
      anterior uveitis as one of the extra-articular manifestations, and familial
      occurrence of ankylosing spondylitis is rarely observed. There is a virtual
      absence of ankylosing spondylitis even in the west African countries of Gambia
      and Senegal, where 3% to 6% of the general population has HLA-B27. The epidemic
      of HIV infection in sub-Saharan Africa in recent years, however, has been
      associated with a dramatic upsurge in the prevalence of spondyloarthropathies
      other than ankylosing spondylitis, primarily reactive arthritis and
      undifferentiated forms of the disease, and less often psoriatic arthritis. HLA
      B27, because of its rarity and virtual lack of association with the observed
      cases of spondyloarthropathy in this population, cannot be used as an aid to
      diagnosis of spondyloarthropathy in black Africans. Conversely, HIV infection is
      increasingly showing such a strong association with reactive arthritis, psoriatic
      arthritis, and undifferentiated spondyloarthropathies in sub-Saharan African
      populations that any patient with acute or chronic inflammatory arthritis may
      need to be tested for possible HIV infection. More research is needed on the
      evaluation of risk and protective factors in sub-Saharan African populations to
      better delineate the relative importance of genetic and environmental factors in
      the pathogenesis of spondyloarthropathies.

PMID- 10910181
TI  - Parvovirus-associated arthritis.
AB  - Human parvovirus B19 is the cause of several distinct clinical syndromes. The
      most common is erythema infectiosum (fifth disease), a febrile exanthem occurring
      primarily in children. Recent studies have shown that parvovirus B19 can cause
      acute arthritis and occasionally a chronic arthropathy, both in children and
      adults. Parvovirus B19 DNA has been detected in studies in the synovial tissue of
      patients with rheumatoid arthritis, but other studies have varied in their
      findings. Recent studies also indicate a possible connective tissue disease-like
      syndrome with parvoviral infections. The common features of this syndrome are
      malar eruption, arthralgias, arthritis, and laboratory abnormalities including
      antinuclear antibody and rheumatoid factor positivity. However, the data indicate
      it is unlikely that B19 infection causes rheumatoid arthritis or systemic lupus
      erythematosus. Continued studies of the pathogenesis of acute and chronic
      parvoviral B19 infections and arthropathy may provide insights into virus-host
      interactions and mechanisms of joint disease and connective tissue disease.

PMID- 10910182
TI  - Hepatitis C-associated arthritis.
AB  - Rheumatologic complications of hepatitis C virus (HCV) infection are common and
      include mixed cryoglobulinemia, vasculitis, sicca symptoms, myalgia, arthritis,
      and fibromyalgia. The prevalence of cryoglobulinemia in Sweden and Germany is
      much lower compared with data from southern Europe. Viral, genetic, or
      environmental factors may be responsible for such a difference in prevalence.
      There is no single clinical picture of arthritis in patients with HCV infection.
      There is a well-defined picture of arthritis associated with the presence of
      mixed cryoglobulinemia that consists of an intermittent mono- or oligoarticular,
      nondestructive arthritis affecting large and medium-size joints. Involvement of
      salivary and lacrimal glands is common in HCV-infected subjects, but HCV antigens
      are not detected in affected glands. HCV-infected subjects express a high
      prevalence of a variety of autoantibodies, usually in low titers. The clinical
      significance of most of these autoantibodies is not clear. The prevalence and
      titer of these autoantibodies are unaffected by interferon-alpha therapy. Several
      studies have attempted to assess whether HCV infection may be involved in the
      etiopathogenesis of rheumatic and autoimmune diseases. The results of most of
      these studies do not support the idea that HCV infection may play a pathogenic
      role in the development of systemic lupus erythematosus, antiphospholipid
      syndrome, or leukocytoclastic vasculitis. Experience treating patients with HCV
      associated arthritis is limited and treatment remains controversial. No major
      therapeutic trials in HCV-associated arthritis were reported in the past 2 years.

PMID- 10910184
TI  - Poststreptococcal reactive arthritis.
AB  - The occurrence of an entity designated poststreptococcal reactive arthritis
      (PSReA) has been highlighted in recent reports. The syndrome was considered part
      of the spectrum of acute rheumatic fever by some, whereas others stressed the
      differences between the two diseases. As distinct from acute rheumatic fever,
      PSReA is characterized by a shorter latency period between the inciting
      streptococcal infection and the onset of arthritis, a higher frequency of
      involvement of the small joints and axial skeleton, poor response to aspirin and
      other nonsteroidal anti-inflammatory drugs, a protracted course of arthritis, a
      low incidence of carditis, and absence of other major manifestations of acute
      rheumatic fever. Recent studies have demonstrated an increased frequency of
      DRB1*01 in patients with PSReA, which contrasts with the increased frequency of
      DRB1*16 in rheumatic fever. Because 6% of patients with PSReA have been reported
      to have late onset carditis, it is judicious to recommend that patients with
      PSReA receive prophylactic antimicrobials for a minimum period of 5 years or
      until the age of 21 years, whichever is longer.

PMID- 10910183
TI  - Reactive arthritis.
AB  - During the past year, no big advances were reported in understanding the
      pathogenesis or treatment of reactive arthritis (ReA). The need for generally
      accepted diagnostic criteria has become a central issue. Regarding pathogenesis,
      attention has been drawn to a similarity between ReA and the experimental antigen
      induced arthritis. Molecular mechanisms of the HLA-B27-associated pathogenesis
      have remained, in spite of intensive research, so far a mystery. It is apparent
      that antibiotics have no effect on the fully developed reactive arthritis, with
      the exception of patients with Chlamydia-triggered ReA, who might benefit from a
      course of antibiotics.

PMID- 10910185
TI  - Lyme disease.
AB  - Lyme disease (LD) is the most common tick-borne disease in the US. The overall
      trend has been an average annual increase in cases since surveillance was
      initiated by the Centers for Disease Control and Prevention in 1982. To date, 10
      different Borrelia species have been described within the Borrelia burgdorferi
      sensu lato complex, although only Borrelia burgdorferi sensu strico, Borrelia
      garinii, and Borrelia afzelii have been associated with human disease. Ixodes
      ticks often carry more than one potential pathogen, and co-infection with B.
      burgdorferi and other organisms have been reported. Recent findings suggested
      that maintenance cycles of other tick-borne pathogens may be different than those
      for B. burgdorferi. A better understanding of the pathogenesis of Lyme arthritis
      has provided clues about the mechanisms responsible for variation in clinical
      expression of the disease. Results of therapeutic trials in Lyme neuroborreliosis
      are likely to have an impact upon treatment recommendations. A long term follow
      up study of children treated for LD indicated that the prognosis is excellent in
      most cases. A safe vaccine for the prevention of LD has been approved in adults.
      Preliminary data suggested that the vaccine is safe and immunogenic in children.

PMID- 10910186
TI  - Bone sarcoidosis.
AB  - Sarcoidosis is a disease that exhibits extremely heterogeneous clinical
      manifestations. Although the lungs are the most commonly involved organs, the
      extension of the granulomatous process may also affect the bones. Almost any bone
      can be involved; curiously, the small bones of the hands and feet are most
      frequently affected. Diagnosis and recognition of osseous sarcoidosis is easy,
      but the therapy is disappointing. Corticosteroids and antimalarials may control
      pain and swelling, but usually do not influence the course of osseous
      sarcoidosis.

PMID- 10910187
TI  - Treatment of bone diseases with bisphosphonates, excluding osteoporosis.
AB  - The main biologic action of bisphosphonates consists of the inhibition of
      osteoclastic bone resorption, and, at least, for the drugs introduced after
      etidronate, without any significant inhibition of bone mineralization.
      Bisphosphonates therefore play a major role in conditions that are characterized,
      at least partly, by an increased bone resorption. Primary and secondary
      osteoporosis by far constitute the most widespread indications for
      bisphosphonates, mostly because recent published trials have demonstrated their
      ability to prevent fractures. Potentially crippling conditions such as
      symptomatic Paget disease of bone remain a major therapeutic challenge for
      bisphosphonates, but the prevention of the major complications such as sarcoma
      has still to be proven. The availability of more potent bisphosphonates, less
      toxic for bones, has certainly widened the therapeutic interventions to
      asymptomatic patients, bearing in mind the various potential troublesome
      complications. Fibrous dysplasia resembles, in certain aspects, Paget disease; it
      is therefore not surprising that bisphosphonate therapy has been proposed in this
      indication. With the aging of world populations, more and more cancers will be
      diagnosed. For those with a bone metastatic propensity or malignant hematologic
      condition, such as multiple myeloma, the most recent generation of more potent
      bisphosphonates may bring more comfort to crippled patients and even, hopefully,
      have a direct antitumoral activity, if used synergistically with the
      armamentarium already available to the clinician. New indications for
      bisphosphonates include osteogenesis imperfecta both in children and adults. In
      the future, they might be used in the prevention of erosions in rheumatoid
      arthritis and of loosening of joint prostheses, as well as possibly in
      osteoarthritis. Now that the fear of theoretically freezing bone remodeling has
      been reasonably dismissed, potential uses for bisphosphonates might be considered
      nearly infinite.

PMID- 10910188
TI  - Quantitative ultrasound in postmenopausal osteoporosis.
AB  - Ultrasound has been proposed as a low-cost, radiation-free method for
      osteoporosis assessment in postmenopausal women. Large prospective studies have
      shown that ultrasound parameters can be used for fracture risk estimate in this
      population, providing that adequate quality control is performed. The places of
      both ultrasound and the current gold standard method for bone assessment, dual
      energy x-ray absorptiometry, are still to be determined. Further studies are
      needed on the diagnosis of osteoporosis using ultrasound, because current
      diagnostic thresholds, designed by the World Health Organization, do not apply to
      this-new technology. Monitoring of skeletal changes and treatment effects by
      ultrasound cannot be recommended.

PMID- 10910189
TI  - Effects of growth hormone and insulinlike growth factor-I on body growth and
      adult bone metabolism.
AB  - The anabolic action of growth hormone (GH) on bone is well demonstrated by the
      short stature and delayed bone maturation in children with GH deficiency and in
      acromegalic patients with increased cortical bone mass. The body growth is
      regulated by growth hormone and insulin-like growth factor-I (IGF-I). The classic
      somatomedin hypothesis of this regulation is that most IGF-I in the blood
      originates in the liver and that body growth is controlled by the concentration
      of IGF-I in the blood. We have recently abolished IGF-I production in the livers
      of mice by using the Cre/loxP recombination system. The mice, in which IGF-I
      production had been inactivated in the liver, displayed a more than 80% reduction
      in serum IGF-I. In contrast, they demonstrated a normal postnatal growth,
      indicating that extrahepatic, autocrine/paracrine-acting IGF-I is the main
      determinant of postnatal growth. GH is also important for normal adult bone
      remodeling. Adults with GH deficiency have reduced bone mass, and GH treatment
      increases bone mass in GH-deficient adults. Future clinical studies will
      determine whether some patients with decreased bone mass for other reasons will
      benefit from treatment with GH alone or in combination with other treatments.

PMID- 10910190
TI  - Hyperparathyroidism: the limits of surgery in cases of bone or cardiovascular
      involvement.
AB  - In primary hyperparathyroidism (PHPT), asymptomatic bone disease can be detected
      by bone densitometry. The bone mineral density is about 10% lower than normal
      control values, especially in the cortical radius. Without parathyroidectomy,
      bone mineral density is frequently stable, but a few patients, mostly
      postmenopausal women, have a significant decrease. Histology shows maintenance of
      trabecular connectivity but with an increase in cortical porosity. After
      parathyroidectomy, bone mineral density increases, particularly at the lumbar
      spine and femoral neck, and the benefit persists after 10 years. The fracture
      risk is controversial but risk of trabecular bone fracture may be higher than
      that for controls. The impact of PHPT on survival is also controversial, but
      highest quartile of serum calcium, osteoporosis, old age, and low lean mass are
      each associated with a death risk. There is also a debate about the criteria for
      distinguishing between asymptomatic and symptomatic PHPT and about the bone
      mineral density threshold that should be used as a basis to recommend surgery.
      The rate of progression of PHPT is slow but in some cases bone loss progresses,
      justifying bone mineral density follow-up. The frequency of inadequate follow-up
      and the cost of nonoperative follow-up are in favor of recommending surgery. With
      broader indications for surgery, it is mandatory to improve the biochemical
      diagnosis of PHPT.

PMID- 10910192
TI  - Bibliography. Current world literature. Infectious arthritis and immune
      dysfunction.

PMID- 10910191
TI  - Bibliography. Current world literature. Spondyloarthropathies.

PMID- 10910193
TI  - Bibliography. Current world literature. Metabolic bone disease.

PMID- 10910195
TI  - Incipient ovarian failure and premature ovarian failure show the same
      immunological profile.
AB  - PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual
      cycles, infertility and a raised early-follicular FSH in women under 40. IOF
      might be a precursor or a mitigated form of premature ovarian failure (POF).
      Disturbances in the immune system may play a role in ovarian failure. METHOD OF
      STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients,
      50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did
      not differ between the groups. There was a statistically significant difference
      in lymphocyte subsets between the control group and the POF group, with the IOF
      group taking an intermediate position. We found a decrease in percentage of T
      suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in
      natural killer cells, and an increase in B lymphocytes and HLA-DR positive T
      cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form
      of POF. The question remains whether these changes are the cause or the
      consequence of the ovarian failure.

PMID- 10910194
TI  - Mammary glands of Aly mice: developmental changes and lactation-related
      expression of specific proteins, alpha-casein, GLyCAM-1 and MAdCAM-1.
AB  - PROBLEM: (1) Aly mouse is an autosomal recessive mutant mouse that lacks lymph
      nodes and Peyer's patches. Defects of mammary glands might explain why these mice
      fail to nurture their pups. (2) Expressions of glycosylation-dependent cell
      adhesion molecule 1 (GlyCAM-1) and mucosal addressin cell adhesion molecule-1
      (MAdCAM-1) in mammary glands of lactating mice have been suggested, but only
      scant information is available. METHODS: The thickness and weight of mammary
      glands were measured directly. The expression of specific proteins, alpha-casein,
      GlyCAM-1, and MAdCAM-1 in mammary glands was detected by reverse transcription
      polymerase chain reaction (RT-PCR). MAdCAM-1 expression was also confirmed by
      immunohistochemistry (IHC). RESULTS: Fat pads of mammary glands of homozygous
      (aly/aly) mice were small and weighed less than those of heterozygous (aly/+ )
      mice. An increase in end-bud development was evident in aly/aly mice. During
      pregnancy, growth of the mammary gland and alveolar formation were noted in both
      groups. The expression of alpha-casein, GlyCAM-1 and MAdCAM-1 was detected in
      both groups of mice by RT-PCR from late-pregnancy. Immunohistochemically, MAdCAM
      1 was noted in small vessels around the mammary globules. CONCLUSIONS: Our
      results demonstrated marked changes in the structure of the mammary glands of
      aly/aly mice. The expression of lactation-related proteins was detected during
      development, pregnancy, and lactation in both aly/aly and aly/+ mice.

PMID- 10910196
TI  - Conductivity detection of polymerase chain reaction products separated by micro
      reversed-phase liquid chromatography.
AB  - In this paper, we describe the application of micro-reversed-phase high
      performance liquid chromatography (mu-RP-HPLC) for the separation and/or
      purification of polymerase chain reaction (PCR) products with detection
      accomplished using a miniaturized conductivity detector. The conductivity
      detector used two Pt wires and a bipolar waveform applied to the electrode pair
      from which the conductivity of the bulk solution could be measured. In the mobile
      phase used for the mu-RP-HPLC separation of the PCR product, the mass detection
      limit for herring sperm DNA using conductivity was found to be 11 ng. Efficient
      separation of the PCR amplicon from the other reagents present in the PCR
      cocktail was achieved in less than 4 min with a capacity factor of 2.5 and
      separation efficiency of 9.1 x 10(3) plates. The separation was carried out using
      reversed-phase ion-pair chromatography with a triethylammonium acetate ion
      pairing agent.

PMID- 10910197
TI  - Hydrodynamic aspects of slurry packing processes in microcolumn liquid
      chromatography.
AB  - A Stokesian dynamics computer simulation based method is presented for the
      estimation of the bed porosity of slurry-packed capillary liquid chromatography
      (LC) columns. A colloidally well-described reversed-phase stationary phase-slurry
      liquid suspension was used as a model system. The applied simulation method takes
      into account the velocity of the slurry and colloidal interaction forces, as well
      as inter-particle hydrodynamic interactions. The predicted bed porosities suggest
      that a lower slurry velocity leads to a denser packing structure due to the
      increased effect of colloidal repulsion effects. The results of the simulations
      were compared with the external porosity and chromatographic performance of
      capillary LC columns that were packed at different filtration and compaction
      pressures. However, the trends that were observed in the experimental results
      suggest that hydrodynamic packing parameters have no or little effect on the
      chromatographic performance of capillary LC columns. Within the experimental
      parameter window, the chromatographic performance and the column porosity were
      not influenced by the filtration and compaction pressure, nor by the duration of
      the compaction process.

PMID- 10910198
TI  - New stationary phase for liquid chromatography with chemically bonded pinane
      ligand: synthesis and characterization by nuclear magnetic resonance and high
      performance liquid chromatographic investigations.
AB  - A new bicyclic phase for liquid chromatography was prepared by solution
      polymerization approaches. To introduce a C4 spacer the starting molecule 3
      formylpinane was reduced to the alcohol followed by a substitution of the hydroxy
      group through a bromide. The obtained halide reacted with magnesium and allyl
      bromide to the 3-(but-3'-enyl)pinane which was hydrosilylated with
      trichlorosilane and finally immobilized to silica gels with different pore sizes
      using the technique of solution polymerization. To elucidate the structure of 3
      (but-3'-enyl)pinane high-resolution two-dimensional nuclear magnetic resonance
      (NMR) spectra were carried out. The new phases were characterized, on the one
      hand by employing 13C and 29Si solid-state NMR spectroscopy and on the other
      hand, by separating a standard test mixture consisting of mainly monosubstituted
      aromatic compounds. The results achieved in chromatography were correlated with
      the information gained from 29Si CP/MAS NMR measurements.

PMID- 10910199
TI  - Pore size distributions of cation-exchange adsorbents determined by inverse size
      exclusion chromatography.
AB  - The pore dimensions, pore size distributions, and phase ratios were determined
      for a set of cation-exchange adsorbents using inverse size-exclusion
      chromatography (ISEC). The adsorbents examined represent a diverse set of
      materials from Pharmacia, TosoHaas, BioSepra, and EM Industries, which are widely
      used for protein purification. The ISEC was carried out using dextran standards
      with relative molecular masses of 180-6,105,000. This technique provided a
      comparative characterization of the accessible internal pore surface area, as a
      function of solute size, for the adsorbents tested. Adsorbent preparation
      strategies in which polymers are generated in situ or grafted onto base materials
      were found to have significant effects on pore dimensions and phase ratios.

PMID- 10910200
TI  - Fullerenes separation with monomeric type C30 stationary phase in high
      performance liquid chromatography.
AB  - The temperature effect on the separation of fullerenes in LC was examined using
      monomeric type C30, C18 and C8 alkyl bonded stationary phases. It appears that
      the C30 phase exhibits superior separation ability for fullerenes. It is observed
      that the maximum retention temperature of fullerenes on the C30 phase is around
      20 degrees C. A strong correlation between the changes in NMR spectra and the
      retention behavior of the solutes was found. The interpretation of the retention
      behavior of fullerenes on the alkyl bonded stationary phases, including the
      behavior in subambient temperature, is discussed using the information obtained
      by CP-MAS solid-state NMR spectroscopy and LC.

PMID- 10910202
TI  - Investigation of combwax of honeybees with high-temperature gas chromatography
      and high-temperature gas chromatography-chemical ionization mass spectrometry.
      II: High-temperature gas chromatography-chemical ionization mass spectrometry.
AB  - Crude combwax of six various honey bee species have been analyzed by high
      temperature gas chromatography (HTGC)-chemical ionization mass spectrometry after
      a two-step silylation procedure. An optimized chromatographic procedure,
      described previously, enables the separation of high-molecular mass lipid
      compounds resulting in a characteristic fingerprint of the combwaxes of different
      honeybee species. The coupling of HTGC to mass spectrometry requires appropriate
      instrumentation in order to achieve sufficient sensitivity at high elution
      temperatures and avoid loss of chromatographic resolution. Chemical ionization
      was carried out using methane as reagent gas in order to determine the molecular
      mass of the individual compounds by means of abundant quasi molecular ions. To
      confirm the presence of unsaturated wax esters, ammonia was used as reagent gas.
      More than 80 lipid constituents were separated and characterized by their mass
      spectra. Representative chemical ionization mass spectra of individual compounds
      are presented. Both, HTGC-flame ionization detection data and the results of the
      HTGC-mass spectrometric investigations enabled a rapid profiling of the
      individual classes of compounds in crude combwaxes.

PMID- 10910201
TI  - Preparative isolation and purification of notopterol and isoimperatorin from
      Notopterygium forbessi Boiss (Chinese traditional medicinal herb) by high-speed
      counter-current chromatography.
AB  - Preparative high-speed counter-current chromatography was successfully used for
      isolation and purification of coumarins from Chinese traditional medicinal herb
      Notopterygium forbessi Boiss (Qianghuo in Chinese) using stepwise elution with a
      pair of two-phase solvent systems composed of light petroleum-ethyl acetate
      methanol-water at volume ratios of 5:5:4.8:5 and 5:5:5:4. Four major components
      including notopterol and isoimperatorin were isolated, each at over 98% purity.

PMID- 10910203
TI  - Quantitative analysis of mutagenic heterocyclic aromatic amines in cooked meat
      using liquid chromatography-atmospheric pressure chemical ionisation tandem mass
      spectrometry.
AB  - Five mutagenic heterocyclic aromatic amines (HAAs) were quantified from meat
      extracts, and grilled and pan fried bacon samples using stable isotopically
      labeled internal standards. These compounds were isolated from the matrices by a
      tandem solid-phase extraction procedure, followed by separation on reversed-phase
      liquid chromatography (HPLC) and quantified by atmospheric pressure chemical
      ionization tandem mass spectrometry (APCIMS-MS). Tandem mass spectrometry (MS-MS)
      acquisition was done in selected reaction monitoring (SRM) mode to provide a high
      degree of sensitivity and selectivity for accurate quantification of HAAs. The
      detection and quantification limits of these HAAs approached 0.015 and 0.045
      microg/kg (part-per-billion), respectively, with only 4 g of meat. The HAA levels
      ranged widely from 0.045 to 45.500 microg/kg, and 2-amino-3,8-dimethylimidazo[4,5
      f]quinoxaline (MeIQx) was the predominant HAA found in these samples. The amount
      of HAAs formed was highly dependent upon the type of meat and method of
      preparation. An intralaboratory comparison of the extraction procedure showed
      that estimates of these HAAs obtained by three different individuals at HAA
      levels below 2 microg/kg were within 5% with coefficients of variation below 19%,
      indicating the robustness of the analytical method. Moreover, because all of
      these HAAs from this class of molecules undergo facile cleavage at the N
      methylimidazole moiety under collision-induced dissociation (CID) conditions, MS
      MS analysis in the constant neutral loss mode of [M+H]+-15 enabled the
      identification of two other HAAs, 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx)
      and 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMeIgQx), which have
      rarely been reported in cooked meats.

PMID- 10910204
TI  - Isolation and preparative purification of microcystin variants.
AB  - Preparative reversed-phase liquid chromatography was successfully used to purify
      two microcystins (microcystin LR and microcystin LA) from a cyanobacterial
      process waste. The separation protocol involved extraction of lyophilized cells
      by methanol, isolation and concentration by solid-phase extraction, and
      purification by reversed-phase HPLC. Milligram-level loading of microcystins was
      obtained on a solid-phase extraction cartridge packed with 0.5 g of C18
      stationary phase. The separations were first carried out on an analytical column
      and then scaled-up to a preparative column. The microcystins were quantified by
      HPLC and enzyme-linked immunosorbent assay. A method to remove microcystins
      rapidly and economically from the cyanobacterial process waste is also described.

PMID- 10910205
TI  - Determination of neurotoxin 3-N-oxalyl-2,3-diaminopropionic acid and non-protein
      amino acids in Lathyrus sativus by precolumn derivatization with 1-fluoro-2,4
      dinitrobenzene.
AB  - A rapid and simple method is presented for determining neuro-excitatory
      nonprotein amino acid 3-N-oxalyl-2,3-diaminopropionic acid (beta-ODAP) and non
      protein amino acids in Lathyrus sativus. Seed and foliage extracts of Lathyrus
      sativus were treated with 1-fluoro-2,4-dinitrobenzene (FDNB) and a reversed-phase
      high-performance liquid chromatography method (RP HPLC) for the separation of the
      derivatives in the pmol range is reported. The RP HPLC method and a colorimetric
      method were compared for measuring ODAP.

PMID- 10910206
TI  - Chromatographic characterization of molecularly imprinted polymers binding the
      herbicide 2,4,5-trichlorophenoxyacetic acid.
AB  - Two polymers binding the herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
      were prepared by utilising the technique of the non-covalent molecular imprinting
      polymerisation in an aqueous medium. The polymers obtained were packed in HPLC
      columns and the effects of the mobile phase composition on the retention of the
      imprinting molecule and the selectivity of the stationary phases towards several
      analogous structures were studied by liquid chromatography. The columns showed a
      good level of selectivity towards the template and strictly related molecules. It
      was found that the molecular recognition mechanism acting on the columns was
      dependent on a combination of ion pair and hydrophobic interactions.

PMID- 10910207
TI  - Improved scheme of chelation ion chromatography with a mixed eluent for the
      simultaneous analysis of transition metals at microg l(-1) levels.
AB  - An improved scheme of chelation ion chromatography (CIC) system and a mixed
      eluent for the simultaneous determination of transition metals are described. A
      method based on the improved CIC system and the mixed eluent
      (PDCA/Na2C2O4/LiOH/NaCl) for the analysis of seven metals (Pb2+, Cu2+, Ni2+,
      Zn2+, Co2+, Cd2+ and Mn2+) at microg l(-1) levels in a single isocratic elution
      is developed. The optimize conditions which are different from references for
      analyte concentration and chromatographic separation are studied in detail. D418
      chelation resin is used to further reduce values of the reagent blank. The above
      seven metals are measured at 565 nm using 2-[(5-Bromo-2-Pyridyl)-Azo]-5-Diethyl
      AminoPhenol(5-Br-PADAP) as the post-column derivatizing reagent. Detection limits
      range from 0.3 to 12 microg l(-1) when 4 ml of sample is pre-concentrated. The
      results of real sample analysis are satisfactory.

PMID- 10910208
TI  - Insoluble beta-cyclodextrin polymer for capillary gas chromatographic separation
      of enantiomers and isomers.
AB  - An insoluble beta-cyclodextrin polymer cross-linked with identified
      epichiorohydrin has been prepared; its structure was identified by means of
      infrared and 13C NMR spectra. Three capillary columns have been coated with the
      polymer treated by ultrasonication by three coating methods. Chromatographic
      characteristics such as column efficiency, thermal stability and polarity, have
      been studied, and two kinds of disubstituted benzene isomers and eight pairs of
      enantiomers have been separated on the three capillary columns. The results show
      that the beta-cyclodextrin polymer is suitable for use as a capillary gas
      chromatographic stationary phase, and that the column, prepared by loading beta
      cyclodextrin polymer stationary phase with 50% methyl-50% phenylsilicone (OV-17),
      shows good chromatographic properties in separating enantiomers and positional
      isomers.

PMID- 10910209
TI  - Novel use of a dual-zone restricted access sorbent: normal-phase solid-phase
      extraction separation of methyl oleate from polynuclear aromatic hydrocarbons
      stemming from semi-permeable membrane devices.
AB  - A normal-phase solid-phase extraction (SPE) method was developed utilizing a dual
      zone restricted-access sorbent to separate methyl oleate from the 16 US
      Environmental Protection Agency priority-pollutant polynuclear aromatic
      hydrocarbons in a hexane matrix. This technique represents a new development in
      SPE methodology expanding the limited number of available normal-phase SPE
      sorbents. While based on a specific application (removal of methyl oleate from
      semipermeable membrane device extracts), this cleanup method could easily be
      adapted for other uses requiring the removal/isolation of methyl oleate and
      potentially related compounds.

PMID- 10910211
TI  - Preparation of 4,4'-(1-[(2)H6]methylethylidene)bis-[2,3,5,6-(2)H4]phenol and its
      application to the measurement of bisphenol A in beverages by stable isotope
      dilution mass spectrometry.
AB  - The preparation of 4,4'-(1-[(2)H6]methylethylidene)bis-[2,3,5,6-(2)H4]phenol,
      bisphenol A-d14, was achieved in excellent yield by reaction of [2H6]acetone with
      [2H6]phenol in the presence of deuterium chloride. The product thus obtained was
      shown by mass spectroscopy to be a mixture of the 2H14, 2H13 and 2H12 isotopomers
      in the relative proportions of 82.3:16.2:1.5, respectively. An isotope dilution
      gas chromatography-mass spectrometric method using bisphenol A-d14 as an internal
      standard was developed to measure the level of bisphenol A in beverages. The
      procedure involves extracting bisphenol A into dichloromethane, and then
      purifying the analyte by back extraction into dilute aqueous sodium hydroxide.
      Conversion of bisphenol A and its internal standard, bisphenol A-d14, to their
      corresponding O-bis(trifluoroacetyl) derivatives by treatment with
      trifluoroacetic anhydride gave compounds with good chromatographic properties and
      whose mass fragmentometry is such that loss of M-CH3 and M-C2H3 are the base
      peaks in the mass spectra of the analyte and internal standard, respectively.
      Quantification of bisphenol A was achieved by comparing the area of the M-15 ion
      to that of the corresponding ion of bisphenol A-d14. The characteristics of our
      assay are: an analyte recovery of better than 95%, a root mean square signal-to
      noise ratio of 79:1 for 1.7 pg on column and an inter-assay RSD of better than 4%
      (n=5).

PMID- 10910210
TI  - Pressurised liquid extraction of polycyclic aromatic hydrocarbons from
      contaminated soils.
AB  - The reliability and efficiency of the pressurised liquid extraction technique
      (PLE) for extracting polycyclic aromatic hydrocarbons (PAHs) from contaminated
      soil has been investigated. Experimental design was used to study the influence
      of seven extraction variables (sample load, solvents used, solvent ratios,
      pressure, temperature, extraction time, and rinse volume). The results show that
      large sample loads in combination with small solvent volumes may result in low
      extraction efficiency. They also indicate that the recovery of low-molecular-mass
      PAHs is reduced by low extraction temperatures. The exact settings of the other
      variables are, however, less significant for the extraction efficiency. Repeated
      extractions at optimised settings of the tested variables show that PLE is an
      exhaustive extraction technique that generally results in high yields. In
      addition, extraction of a certified reference material (CRM 103-100) revealed
      that the method is both accurate and precise. Another finding was that adding the
      internal standard on top of the soil in the extraction cell causes considerable
      over-estimation of the concentrations when large samples are extracted with small
      solvent volumes. This is because the PLE-cell resembles a chromatographic column,
      so compounds added to the top of the soil layer have a longer distance to travel
      through the soil compared to the average distance of the native compounds, which
      are distributed evenly throughout the column. We therefore recommend that the
      internal standard should be added to the extract immediately after the extraction
      or, alternatively, carefully mixed with the sample prior to extraction.

PMID- 10910212
TI  - Dynamic system for the calibration of semi-volatile carbonyl compounds in air.
AB  - A dynamic calibration system designed for generating accurate and precise
      concentrations of semi-volatile carbonyls in the ppb (v/v) (ppbv)-ppt (v/v)
      (pptv) range has been developed and tested. Alkanals from C6 to C9 were used as
      test compounds. Diffusion rates of their vapours from capillary tubes were
      determined theoretically and with two methods whose accuracy was independently
      evaluated with liquid standard solutions. Methods selected for testing the
      calibration system were those commonly used for the selective quantification of
      carbonyls in air. One is based on the well-known reaction with 2,4
      dinitrophenylhydrazine (DNPH), followed by the analysis of formed hydrazones by
      HPLC-UV. The other is based on the retention of carbonyls on graphitic carbon
      adsorbents, followed by MS detection of the sample injected into a capillary
      column by thermal desorption. A good consistency was found between the values of
      the diffusion rates determined by the two methods. The scatter between the two
      methods was in the range of +/-10% when diffusion rates of ca. 1 ng/s were
      attained. Experimental values closely approached those calculated by applying the
      equation describing the diffusion of a vapour in equilibrium with the liquid
      through a capillary tube.

PMID- 10910213
TI  - Multiple-technique analytical characterization of a mixture containing chemical
      weapons simulant from a munition.
AB  - An amber yellow organic liquid was found in a munition shell at Dugway Proving
      Grounds, UT, USA, that was likely used as a simulant of chemical weapons. The
      primary analytical techniques to characterize the mixture were gas chromatography
      infrared detection-mass spectral detection (GC-IR-MS); liquid chromatography-mass
      spectrometry (LC-MS); nuclear magnetic resonance (NMR) using the nuclei 1H, 13C
      and 31P; and gas chromatography-atomic emission detection (GC-AED). Six major
      phosphorus-containing components were identified and confirmed by at least three
      techniques, and several additional phosphorus-containing components of lower
      concentration have been identified by GC-IR-MS and LC-MS. Five major non
      phosphorus components, including ethyl acetate, diethyl sulfide and dibutylamine,
      have been identified by multiple techniques. The major phosphorus compound
      (23.9+/-0.4 wt.%) was O,O,O-triethyl phosphorothioate (I) and the second most
      abundant (14.4+/-0.2 wt.%) was O,O,S-triethyl phosphorothioate (III). No VX, G
      agent, or pesticide was observed in the sample, although III may be a
      cholinesterase inhibitor which produces delayed toxic response. III also produces
      a false hit for the pesticide cyanthoate when analyzed by GC-MS-EI. The mixture
      appears to have been formulated as a chemical warfare agent simulant, most likely
      as a challenge of agent detection techniques.

PMID- 10910214
TI  - Polymer additive analysis by pyrolysis-gas chromatography. I. Plasticizers.
AB  - Plasticizers are widely used in thermoplastic polymers to modify their physical
      properties and processibility. Plasticizers as well as most of the other
      additives in the polymer can be qualitatively analyzed by pyrolysis-gas
      chromatography (Py-GC) simultaneously with the polymer composition. The key to
      the successful analysis of plasticizers not only requires a comprehensive
      understanding of commercial plasticizers but also requires knowledge of the
      polymer and its applications, as well as the Py-GC technique. In this study,
      several plasticizers in different polymeric systems were studied to demonstrate
      the utility of Py-GC as a good tool for the characterization of these systems.
      The advantages of using Py-GC for plasticizer analysis are also discussed.

PMID- 10910215
TI  - Retention behaviour of ceramides in sub-critical fluid chromatography in
      comparison with non-aqueous reversed-phase liquid chromatography.
AB  - This study was devoted to the development of an analytical method for ceramide
      analysis in packed subcritical fluid chromatography (pSubFC). Monofunctional
      grafted silica support was found to be more suitable for ceramide analysis. Five
      Kromasil columns were coupled and the parameters, temperature, pressure and
      percentage of organic modifier in CO2 were optimised, considering selectivity and
      analysis time. The final conditions were 31 degrees C, 6% of methanol (MeOH) and
      13 MPa. In these conditions the selectivity for structural differences (methylene
      group, unsaturation or two different bases) were studied. As classically
      observed, the methylene selectivity decreased with the increase of the eluotropic
      strength. Moreover, unlike in non-aqueous reversed-phase liquid chromatography
      (NARP-LC), adding a further unsaturation and two further methylene groups on
      ceramide results to an increase of retention in pSubFC. Moreover, this last
      technique allowed to separate ceramides with the same total number of carbons
      containing unsaturated fatty acids, when the distribution of carbon number of the
      two chain is very different. These results had enabled to plot retention chart in
      order to predict ceramide structure in view to identify additional ceramide. This
      retention chart was finally compared with the one already obtained in NARP-LC.

PMID- 10910216
TI  - Split-flow injector for capillary zone electrophoresis.
AB  - A simple construction of a split-flow injector eliminating some common problems
      connected with the use of such devices is described. It consists of a low
      pressure pump, an injection valve and a delivery tube in which the separating
      capillary inlet is fixed. The sample is injected without moving the separating
      capillary inlet and without interrupting the applied voltage. The grounded
      electrophoretic electrode is close to the injection valve so that all metal parts
      of the injector are kept at a sufficiently low potential. Minimum length and
      small internal diameter of delivery tube minimizes additional sample zone
      broadening. The effects of some experimental parameters, such as the position of
      the separation capillary inlet with respect to the background solution flow
      direction and background solution flow-rate are experimentally studied. The
      injector was tested primarily for the electrokinetic injection.

PMID- 10910218
TI  - Fast development of separation methods for the chiral analysis of amino acid
      derivatives using capillary electrophoresis and experimental designs.
AB  - The use of experimental design in method development was studied for the chiral
      separation of several amino acid derivatives with capillary electrophoresis. The
      aim of this study was to define rapidly experimental conditions under which the
      enantiomers can be sufficiently separated for quantification and to derive a
      methodology for the separation of new compounds. Three modified cyclodextrins
      (CDs) were used as chiral selectors: hydroxypropyl-beta-cyclodextrin,
      carboxymethyl-beta-CD and sulfobutylether-beta-CD. The following factors were
      examined: the type of cyclodextrin, the CD concentration, the pH and the % of
      organic modifier (methanol) of the electrolyte. Two types of fractional factorial
      design were used depending on the type of analyte and on the number of factors
      selected: a 3(4-2) fractional factorial design (4 factors studied at 3 different
      levels) and a 2(3-1) fractional factorial design (3 factors at 2 different
      levels). From the 14 compounds investigated, 12 could be separated with one or
      another CD and not more than 9 experiments were required. No generalisation of
      the best analysis conditions was possible within this family of compounds.
      Specific analysis conditions must be defined for each analyte. Experimental
      designs have shown to be very useful to determine rapidly conditions under which
      each enantiomer can be separated with an acceptable resolution.

PMID- 10910217
TI  - Laser-induced dispersed fluorescence detection of polycyclic aromatic compounds
      in soil extracts separated by capillary electrochromatography.
AB  - Polycyclic aromatic hydrocarbons (PAHs) and nitrogen containing aromatic
      compounds (NCACs) are characterized in soil extracts and laboratory standards by
      capillary electrochromatography (CEC) with laser-induced dispersed fluorescence
      (LIDF) detection using a liquid-nitrogen cooled charge-coupled device detector.
      The LIDF detection technique provides information on compound identity and, when
      coupled with the high separation efficiencies of the CEC technique, proves useful
      in the analysis of complex mixtures. Differences in fluorescence spectra also
      provide a means of identifying co-eluting compounds by using deconvolution
      algorithms. Detection limits range from 0.5 to 96x10(-10) M for selected PAHs and
      0.9-3.7x10(-10) M for selected NCACs. Soil extracts are also injected onto the
      CEC column to evaluate chromatographic method performance with respect to complex
      samples and the ability to withstand exposure to environmental samples.

PMID- 10910219
TI  - Free solution mobility of DNA molecules containing variable numbers of cationic
      phosphoramidate internucleoside linkages.
AB  - The free solution electrophoretic mobility of an 118-base pair DNA fragment
      containing zero, three, six or nine cationic phosphoramidate internucleoside
      linkages has been measured by capillary electrophoresis. The electrophoretic
      mobility decreases with the increasing number of cationic phosphoramidate
      linkages, as expected because of the reduced negative charge on the DNA
      molecules. The decrease in mobility is approximately linear for DNA molecules
      containing three and six cationic phosphoramidate linkages, but begins to level
      off when nine cationic phosphoramidate linkages have been added. The mobility
      also varies somewhat depending on whether the modified phosphoramidate linkages
      are located at the 5'- or 3'-end of the DNA molecule.

PMID- 10910220
TI  - Determination of sulfonated azo dyes in river water samples by capillary zone
      electrophoresis.
AB  - A method based on capillary zone electrophoresis coupled with photodiode-array
      detection has been developed to determine several sulfonated dyes, including a
      sulfonated dye (acid yellow 1), and the sulfonated azo dyes acid orange 7, acid
      orange 12, acid orange 52, acid red 26, acid red 27 and acid red 88. A CElect
      FS75 CE column is used. The electrophoresis buffer contains a 1:5 dilution of 10
      mM phosphoric acid and tetrabutylammonium hydroxide buffer (pH 11.5), and 25 mM
      of triethylamine, the final pH being 11.55. The detection limits for the seven
      dyes ranged from 0.1 to 4.53 microg/ml. Spiked river water samples (100 ml),
      containing different concentration levels (0.025-0.150 microg/ml) of the dyes
      were analyzed after acidification (pH 3) and pre-concentration in disposable SPE
      Oasis HLB, 1 ml cartridges.

PMID- 10910221
TI  - Validation of a capillary electrophoresis method for determination of 5
      aminolevulinic acid and degradation products.
AB  - A capillary electrophoresis method was developed for simultaneous quantification
      of 5-aminolevulinic acid (ALA) and its degradation products 2,5-dicarboxyethyl
      3,6-dihydropyrazine and 2,5-dicarboxyethylpyrazine in aqueous solution within a
      total analysis time of 9 min. The optimized method was validated with respect to
      specificity, precision, linearity, limits of detection and quantitation, and
      robustness. The degradation products were quantified with respect to the ALA
      peak. A related micellar electrokinetic chromatography method, involving the
      addition of sodium dodecylsulfate to the running buffer solution, was applied for
      direct injection of an oil-in-water emulsion containing ALA, i.e. without sample
      pretreatment.

PMID- 10910222
TI  - High-performance liquid chromatography with multi-wavelength detection of the
      bisphenol A impurities.
AB  - A reversed-phase HPLC method was developed for the analysis of 15 impurities
      present in the process streams from the production of bisphenol A. UV spectra
      were taken for standard components. These were evaluated and the detection
      wavelengths of 254, 280 and 305 nm were selected for the chromatograms to be
      recorded. Concurrent detection at the wavelengths selected of the chromatograms
      taken makes it easier to identify the components and considerably improves the
      accuracy of the quantitative analysis.

PMID- 10910223
TI  - Rapid high-performance liquid chromatography method for the analysis of sodium
      benzoate and potassium sorbate in foods.
AB  - A rapid and reliable method is presented for the determination of the
      preservatives sodium benzoate and potassium sorbate in fruit juices, sodas, soy
      sauce, ketchup, peanut butter, cream cheese, and other foods. The procedure
      utilizes high-performance liquid chromatography (HPLC) followed by UV diode array
      detection for identification and quantitation of the two preservatives. Liquid
      samples were prepared by diluting 1 ml of the sample with 10 ml of an
      acetonitrile/ammonium acetate buffer solution. Samples of viscous or solid foods
      were prepared by blending the sample with the same buffer solution in a 1:5 ratio
      followed by a dilution identical to liquid samples. All samples were filtered to
      remove particulate matter prior to analysis. The HPLC determination of the
      preservatives was performed using a reversed-phase C18 column and UV detection at
      225 nm for sodium benzoate and 255 nm potassium sorbate. The percentage of
      preservative in the sample was calculated by external standard using authentic
      sodium benzoate and potassium sorbate. Apple juice, apple sauce, soy sauce, and
      peanut butter, spiked at 0.10 and 0.050% for both sodium benzoate and potassium
      sorbate, yielded recoveries ranging from 82 to 96%. The method can detect 0.0010%
      (10 mg/l) of either preservative in a juice matrix.

PMID- 10910224
TI  - Sensitive determination of dissolved sulfide in estuarine water by solid-phase
      extraction and high-performance liquid chromatography of methylene blue.
AB  - A sensitive method involving solid-phase extraction and HPLC analysis of
      methylene blue has been developed to measure nanomolar levels of dissolved
      sulfide in oxic surface waters. The procedure included 1) a preconcentration
      step, in which methylene blue generated from sulfide reaction with n,n-dimethyl-p
      phenylenediamine in acidic conditions in the presence of ferric ion was absorbed
      onto Waters tC18 cartridge; and 2) a determination step, in which methylene blue
      was separated by HPLC in a gradient elution to minimize natural organic matter
      interference and detected by absorbance. The concentrations of the dissolved
      sulfide, quantified by standard addition, were about 2.1-4.7 nM in oxic surface
      waters from Galveston Bay, Texas.

PMID- 10910225
TI  - Oral estramustine phosphate and oral etoposide for the treatment of hormone
      refractory prostate cancer.
AB  - BACKGROUND: The purpose of the present study was to evaluate the antitumor
      activity and toxicity of oral estramustine phosphate (EMP) in combination with
      oral etoposide in patients with hormone-refractory prostate cancer. METHODS:
      Twenty patients with adenocarcinoma of the prostate that progressed after one or
      more regimens of androgen-deprivation therapy were enrolled into this trial. Oral
      EMP was administered twice daily, for a total daily dose of 560 mg, and oral
      etoposide (50 mg/bodyweight per day) was given on days 1-21 and was stopped on
      days 22-35. Treatment was continued until evidence of disease progression
      appeared or two consecutive rises in the prostate-specific antigen (PSA) value
      were observed. RESULTS: Ten of 20 patients showed a decrease of 50% or greater in
      the PSA value from initially elevated PSA levels after therapy. The median
      progression-free duration and 2 year cause-specific survival rate of these 10
      patients were 208 days (range 71-693 days) and 67.5%, respectively. There were no
      significant differences in age, pretreatment PSA value, duration from initial
      treatment to relapse, prior therapy or survival between patients who had a
      decrease of 50% or greater in PSA values after this combination therapy and those
      who did not. The main toxicities (> or =grade 2) were anemia, leukocytopenia,
      thrombocytopenia, gastrointestinal and hepatic disorders, which occurred in 40,
      15, 10, 15 and 5% of patients, respectively. CONCLUSIONS: The combination of oral
      EMP and etoposide is considered to be a well-tolerated outpatient treatment
      regimen for patients with hormone-refractory prostate cancer and the therapy
      deserves further investigation.

PMID- 10910226
TI  - Urinary tract cancer screening through analysis of urinary red blood cell volume
      distribution.
AB  - BACKGROUND: Hematuria is differentiated between glomerular and urinary tract
      origins on the basis of urinary red cell morphology. We used this distinction in
      a program of mass screening for urinary tract cancer to achieve cost-effective
      and safe hematuria screening. METHODS: Of a total of 21372 adults (mean age 52.3
      years; range 20-79 years) participating in a health screening, 912 (4.3%) had a
      positive dipstick for hematuria and were enrolled in the present study. Urinary
      red cell volume distribution curves (RDC), the simplest method of assessing
      urinary red cell morphology, were calculated and subjects were divided into two
      groups based on their RDC patterns. Group I subjects had a normocytic or mixed
      pattern and they were immediately investigated for urinary tract malignancy
      because of the associated risk for urological disease. Group II subjects had a
      microcytic pattern and, therefore, were judged to be at a low risk of urologic
      malignancy and were followed up 3 years later without urologic investigations.
      RESULTS: Among the 38 subjects in group I (4% of all dipstick-positive subjects),
      one case of bladder cancer was detected. In the remaining 37 patients, 15 cases
      of benign diseases were discovered. Group II was composed of 869 subjects (96%).
      The inquiry into their health status conducted 3 years later revealed that 831
      (95.6%) were healthy and, of these, 13 had experienced gross hematuria during the
      period but urological malignancies were ruled out by their urologists, two (0.2%)
      had died of diseases other than urological cancer and 36 (4.1%) were lost to
      follow-up. With our method, total costs have been reduced by 93.8% against a
      conventional setting of a full evaluation for all cases of hematuria.
      CONCLUSIONS: Microcytic hematuria, accounting for 96% of asymptomatic
      microhematuria cases in the present study, was not associated with a risk for
      urinary tract malignancy. Compared with conventional hematuria screening with a
      complete work-up of all cases of hematuria, investigating only subjects with
      mixed or normocytic RDC patterns was safe and cost effective.

PMID- 10910227
TI  - Trends and characteristics in prostate cancer mortality in Japan.
AB  - BACKGROUND: In North America, the incidence and mortality of prostate cancer has
      been declining since the early 1990s. We calculated the age-adjusted death rates,
      age-specific death rates and standardized mortality ratio (SMR) for prostate
      cancer in Japan and analyzed their features. METHODS: Yearly age-adjusted death
      rates for prostate cancer were calculated by dividing the number of events by the
      population at risk, with direct standardization to the world population. Age
      specific death rates were calculated for the 1970s, 1980s and 1990s and which age
      group showed the highest rate of increase was examined. The SMR in each
      prefecture was also calculated for each period. RESULTS: The respective number of
      deaths and the age-adjusted death rate was 1107 and 2.29 in 1973 and 6251 and
      5.15 in 1997. The age-specific death rates showed an exponential increase with
      age in all three periods and the rate of increase was higher in older age groups.
      The distribution of SMR showed the same tendency in all three periods. The
      prefectures with significantly high or low SMR were distributed in clusters.
      CONCLUSIONS: The prostate cancer death rate is increasing rapidly in Japan.
      However, the age-adjusted death rate has remained stable from 1996 to 1997. How
      this figure will change and whether the prostate cancer death rate in Japan will
      begin to decline, like in North America, is of interest. The prefectures with
      significantly high or low SMR showed a characteristic clustered distribution
      pattern.

PMID- 10910228
TI  - High-dose chemotherapy with peripheral blood stem cell transplantation for
      advanced testicular cancer.
AB  - BACKGROUND: The present study was performed in order to investigate the efficacy
      and safety of high-dose chemotherapy for the treatment of patients with advanced
      testicular cancer. METHODS: Seven patients were treated with high-dose
      carboplatin, etoposide and cyclophosphamide followed by peripheral blood stem
      cell transplantation. Five patients received one cycle and two patients received
      two cycles of the high-dose chemotherapy. RESULTS: Of the seven patients, one
      achieved a complete response and four achieved partial responses with markers
      negative. As a result of subsequent surgery for residual tumors, three of the
      four partial responders showed no residual cancer cells. One patient who did not
      undergo surgery received radiotherapy after the high-dose chemotherapy and the
      residual tumors disappeared. All five patients who had either a complete or
      partial response are still alive and without evidence of disease at 12, 27, 30,
      37 and 40 months. One patient is alive with disease at 7 months and one died of
      progressive disease at 6 months. The hematologic recovery after high-dose
      chemotherapy was rapid and non-hematologic toxicities were usually mild and
      manageable. CONCLUSIONS: High-dose chemotherapy followed by peripheral blood stem
      cell transplantation is safe and effective for use in patients with far-advanced
      testicular cancer, particularly when the high-dose chemotherapy is conducted as
      the initial treatment. Further larger and long-term follow-up studies are needed
      to define the role of high-dose chemotherapy on testicular cancer.

PMID- 10910229
TI  - Prognostic value of tumor-associated macrophage count in human bladder cancer.
AB  - BACKGROUND: We determined the tumor-associated macrophage (TAM) count to
      investigate its importance in predicting clinical outcome or prognosis in
      patients with bladder cancer. METHODS: The TAM count and microvessel count (MVC)
      were determined immunohistochemically in 63 patients with bladder cancer,
      including 40 superficial bladder cancers and 23 invasive bladder cancers. To
      examine the relationship between TAM count and clinical outcome or prognosis in
      bladder cancer, cystectomy rates, distant metastasis rates, vascular invasion
      rates and 5 year survival rates were compared between patients with low (< 67)
      and high (> or = 67) TAM counts. RESULTS: The TAM count in invasive bladder
      cancers (154.22+/-11.98) was significantly higher than in superficial bladder
      cancers (49.05+/-7.76; P<0.0001). The MVC in invasive bladder cancers (71.55+/
      10.44) was also significantly higher than in superficial bladder cancers (47.02+/
      5.57; P<0.05). There was a positive correlation between TAM count and MVC
      (r=0.30; P=0.02). Immunohistochemical staining using CD68/horseradish peroxidase
      monoclonal antibody showed more infiltrating cells in invasive than superficial
      bladder cancers. Patients with a high TAM count (> or =67) showed significantly
      higher rates of cystectomy, distant metastasis and vascular invasion than those
      with a lower TAM count (<67). The 5 year survival rate estimated using the Kaplan
      Meier method was significantly lower in patients with a high TAM count than in
      those with a low TAM count (P<0.0001). CONCLUSIONS: Our results suggest that
      determination of TAM count in bladder cancer tissues is of value to predict the
      clinical outcome or prognosis and to select appropriate treatment strategies in
      patients with bladder cancer.

PMID- 10910230
TI  - Extracorporeal shock wave lithotripsy for a ureteral stone in crossed fused renal
      ectopia.
AB  - BACKGROUND: A 63-year-old woman presented with right flank pain and macroscopic
      hematuria. RESULTS/METHODS: A plain film showed a calcific shadow on the right
      iliac bone. On excretory urography, the right kidney was seen in the normal
      position, but the left kidney was not. Bilateral retrograde pyelogram revealed
      the S-shaped kidney and mild obstruction from a 12 x 5 mm calculus in the
      proximal ureter of the crossed kidney. The patient was successfully treated with
      in situ extracorporeal shock wave lithotripsy (ESWL) treatment and is stone free
      at 1 month follow up. CONCLUSION: We believe this is the first case of successful
      ESWL in a crossed kidney.

PMID- 10910232
TI  - Epidermoid cyst arising from the spermatic cord area.
AB  - PURPOSE: We report on an epidermoid cyst arising from the spermatic cord area
      that was confirmed histologically after local excision. METHODS/RESULTS:
      Radiologic studies demonstrated a well-encapsulated solid mass in the left
      inguinal region, which was adjacent to the left spermatic cord. Tumor resection
      was then performed. Pathological examination revealed a epidermoid cyst lined
      with keratinized squamous epithelium. CONCLUSION: There was no recurrence
      observed 5 years after surgery.

PMID- 10910231
TI  - Urachal tuberculosis.
AB  - BACKGROUND: We report on an extremely rare case of urachal tuberculosis that was
      confirmed using a polymerase chain reaction test of paraffin-embedded material.
      METHODS/RESULTS: A 62-year-old man presented with pollakiuria. With a diagnosis
      of urachal abscess, the patient underwent en bloc resection of the cystic mass. A
      bacterial culture test of the content showed no organism. The histopathologic
      findings suggested urachal tuberculosis. The AMPLICOR polymerase chain reaction
      test by using paraffin-embedded sections revealed the existence of Mycobacterium
      tuberculosis in the resected tissue. The only positive finding in systemic
      screening examinations for tuberculosis was old tuberculosis scars in the upper
      right lung. It was supposed that hematogeneous spreading from the lung lesion may
      result in urachal tuberculosis after a long latent period. CONCLUSIONS: Although
      urachal tuberculosis is an extremely rare condition, tuberculosis must always be
      kept in mind when observing any infectious diseases.

PMID- 10910233
TI  - Familial adenomatous polyposis: results after ileal pouch-anal anastomosis in
      teenagers.
AB  - PURPOSE: Virtually all untreated patients with familial adenomatous polyposis
      develop colorectal carcinoma. Thus, prophylactic colectomy is indicated.
      Detractors of ileal pouch-anal anastomosis prefer ileorectal anastomosis for
      teenagers because of the potential negative impact of ileal pouch-anal
      anastomosis on quality of life. The aim of this study was to assess the effects
      on quality of life of ileal pouch-anal anastomosis in teenagers with familial
      adenomatous polyposis. METHODS: Between 1981 and 1998, 48 teenagers underwent
      ileal pouch-anal anastomosis for familial adenomatous polyposis. One patient had
      proctectomy and ileal pouch-anal anastomosis after previous ileorectal
      anastomosis. A temporary diverting loop ileostomy was established in 42 patients
      (87.5 percent). One patient had colonic carcinoma diagnosed preoperatively. Two
      other patients were found to have unsuspected rectal cancer at surgery. Mean
      follow-up (+/- standard deviation) in 43 patients was 80.5 +/- 42 months.
      RESULTS: There was no immediate postoperative mortality. Postoperative
      complications included pelvic sepsis (3 patients; 1 requiring reoperation) and
      bleeding (1 patient; no surgery required). One patient died of metastatic colonic
      carcinoma. Ten patients required reoperation, seven had bowel obstruction, one
      had portal hypertension, and two required an ileostomy. The mean (+/- standard
      deviation) daytime and nighttime stool frequency was 4 +/- 1.5 and 1 +/- 1,
      respectively. One patient reported daytime and nighttime incontinence, and two
      patients reported nighttime incontinence only. No patient experienced impotence
      or retrograde ejaculation. Social, sexual, sport, housework, recreation, family,
      travel, and work activities were improved or unchanged in 82.5, 87, 80, 90, 80,
      92.5, 77.5, and 89 percent of patients, respectively. Three male patients
      fathered children, and three female patients had a total of six children after
      normal pregnancies and deliveries. CONCLUSION: The impact of ileal pouch-anal
      anastomosis on quality of life was favorable in the majority of teenagers. The
      risk of rectal cancer should be the major consideration before proposing an
      operation to teenagers with familial adenomatous polyposis.

PMID- 10910234
TI  - Extrafascial excision of the rectum: surgical anatomy of the fascia propria.
AB  - PURPOSE: It is now agreed that it is of vital importance to maintain the fascia
      propria as an intact envelope around the mesorectum to prevent tumor spillage
      while performing rectal excision for cancer. There are several surgical
      techniques described to achieve an intact fascial envelope, each arising from
      differing descriptions of the fascia propria of the rectum. The aim of this study
      was to describe the detailed surgical anatomy of the fascia propria. METHODS:
      Thirteen rectal specimens surgically removed by the technique of extrafascial
      excision were subjected to gross inspection, dissection, and histologic and
      electron microscopic examination. The attachments, thickness, and composition of
      the fascia propria were determined. RESULTS: The fascia propria is a continuous
      fascial sleeve surrounding the rectum and mesorectum that can be dissected as a
      complete "sock" off a fresh extrafascial specimen. It is 154 (+/- 1 standard
      deviation = 61-391) microm thick, is thinner anteriorly than posteriorly (P <
      0.05), and is composed predominantly of collagen. It can be identified surgically
      at the pelvic brim as a shiny membrane and lies inside the hypogastric nerves and
      the pelvic plexuses. CONCLUSION: The fascia propria forms a sleeve around the
      mesorectum, offering a surface against which to dissect, enabling safe removal of
      the rectum with its intact mesorectum while preserving the autonomic nerves of
      the pelvis. The term "extrafascial excision" highlights the importance of the
      fascia propria in this operation.

PMID- 10910235
TI  - Strictureplasty for Crohn's disease: meta-analysis.
AB  - PURPOSE: The objective of this study was to analyze patient outcome after
      strictureplasty for management of intestinal stricture caused by Crohn's disease
      based on differences in surgical procedures. METHODS: A MEDLINE search was
      performed using a medical subject heading analysis for strictureplasty in Crohn's
      disease. Meta-analysis of multiple variables for outcome was performed using
      random-effects models. RESULTS: Five hundred six patients underwent 1,825
      strictureplasties for Crohn's disease with minimal morbidity and zero mortality.
      Ninety percent of strictures were less than 10 cm in length. Approximately 85
      percent of these procedures used the Heineke-Mikulicz technique and 13 percent
      used Finney strictureplasty. Forty-four percent of procedures included concurrent
      bowel resection. Recurrence rate of Crohn's disease after strictureplasty was
      increased in patients with longer study duration after surgery (P = 0.04), who
      showed symptoms of active disease (P = 0.02), who experienced preoperative weight
      loss (P = 0.02), or who received the Heineke-Mikulicz procedure (P = 0.008). The
      proportion of patients requiring additional surgery was increased with longer
      study duration (P = 0.006), with preoperative weight loss (P = 0.001), or with
      the Heineke-Mikulicz procedure (P = 0.005). The proportion of patients requiring
      additional surgery was decreased when a Finney strictureplasty was used (P =
      0.008) as compared with those treated by the Heineke-Mikulicz procedure.
      CONCLUSION: Although the Heineke-Mikulicz technique is most often used for
      Crohn's strictureplasty, outcome analysis revealed the Finney strictureplasty may
      reduce the reoperation rate.

PMID- 10910236
TI  - Strictureplasty in Crohn's disease: surgical option.
AB  - PURPOSE: The objective of this study was to review early and late results of our
      personal experience with strictureplasty for patients affected by Crohn's
      disease. METHOD: During a 16-year period, 44 of 383 patients underwent
      strictureplasty. Of the 269 strictures present at surgery, 174 were treated by
      performing strictureplasties (156 were closed transversely according to the
      Heineke-Mikulicz technique, 16 were done side-to-side in the Finney manner, and 2
      were done according to Jaboulay technique), and 88 were treated with a
      synchronous resection. An individualized technique was used for seven other
      strictures, with side-to-side ileocolic (5 strictures in 3 patients) or ileoileal
      anastomosis (2 strictures in one patient). RESULTS: No operative mortality was
      recorded, nor were septic complications caused by anastomotic leakage observed.
      The mean follow-up period was 47.8 +/- 42.4 (range, 3-132) months. After a median
      follow-up period of 50 (range, 18-89) months, a second operation for symptomatic
      recurrence was performed on ten patients, and two of them developed new
      symptomatic strictures after 3 and 36 months, requiring a third operation.
      Symptomatic restrictures of previous strictureplasty sites requiring surgery
      occurred in 8.8 percent of cases. Furthermore, no statistically significant
      difference (Kaplan-Meier) was observed in the reoperation rate among the patients
      with skip lesions or closed strictures or among patients treated by
      strictureplasty alone or with associated resection. CONCLUSION: We conclude that
      strictureplasty is a valuable adjunct or alternative to resection in the
      treatment of Crohn's strictures.

PMID- 10910237
TI  - Anorectal physiologic testing for bowel dysfunction in patients with spinal cord
      lesions.
AB  - PURPOSE: Bowel dysfunction is common in patients with spinal cord lesions. This
      study aims to determine whether there are any discriminatory findings at
      anorectal physiologic testing in patients with spinal cord lesions. METHODS:
      Twelve consecutive patients (6 females) with significant spinal cord lesions who
      had mixed symptoms of constipation, fecal impaction, and fecal incontinence were
      evaluated by perfusion manometry and pudendal nerve terminal motor latency. None
      of the patients had a sphincter defect as evaluated by endoanal ultrasonography.
      RESULTS: The median age was 54 (range, 40-87) years. Eight (67 percent) of them
      had had traumatic spinal cord injuries. Other spinal cord lesions included spina
      bifida, syringomyelia, arachnoid cyst, and spinal cord ischemia after abdominal
      aortic aneurysm repair. In patients with spinal cord lesions, the mean (range)
      resting anal canal pressure and maximum squeeze anal canal pressure were 46 (10
      100) mmHg and 76 (30-120) mmHg respectively compared with 62 (50-70) mmHg, and
      138 (100-180) mmHg, respectively, in healthy controls. Eleven (92 percent)
      patients had prolonged pudendal nerve terminal motor latency (9 bilateral and 2
      unilateral) whereas rectoanal inhibitory reflex was abolished in all 9 patients
      tested. CONCLUSIONS: Spinal patients with severe bowel symptoms tended to have
      lower anal canal pressures than healthy controls. Pudendal netropathy and
      impaired rectoanal inhibitory reflex are common and may be important in the
      pathogenesis of bowel dysfunction in patients with spinal cord lesions.

PMID- 10910239
TI  - Development of constipation in nursing home residents.
AB  - PURPOSE: Constipation is a common complaint among geriatric patients and may
      result in significant morbidity, especially among nursing home residents. The
      prevalence of constipation increases with advancing age and may be a result of
      the aging process, but the exact cause is unknown. The aim of this study was to
      describe the prevalence of constipation and to determine risk factors for the
      development of constipation in a large population of nursing home residents.
      METHODS: The Minimum Data Set is an assessment instrument used in nearly all
      Medicare-certified and Medicaid-certified nursing facilities. Nursing home
      residents who were at least 65 years of age and who had assessments at baseline
      and at three months were included in the study (N = 21,012). Baseline risk
      factors were included in a multivariate logistic regression to determine their
      association with the development of constipation. To allow causal implications,
      nursing home residents with constipation at baseline were excluded. The variables
      examined included medications, mobility, comorbid illness, and nutrition.
      RESULTS: The mean age (+/- standard deviation) of nursing home residents was 83
      +/- 8 years, and the population was 70 percent female and 83 percent white. At
      baseline, the prevalence of constipation was 12.5 percent (N = 2,627). By the
      three-month assessment, 7 percent (N = 1,291) of nursing home residents had
      developed constipation. The factors associated independently with the development
      of constipation were, in order of magnitude, race, decreased fluid intake,
      pneumonia, Parkinson's disease, and the presence of allergies. Congestive heart
      failure and the use of a feeding tube were two factors identified as having a
      protective effect. CONCLUSION: The variables associated with the development of
      constipation may be used to identify geriatric nursing home residents at risk and
      to prevent constipation and its potential complications. Further study is needed
      to demonstrate a causal relationship between the risk factors and the development
      of constipation.

PMID- 10910238
TI  - Postoperative colonic motility and tone in patients after colorectal surgery.
AB  - PURPOSE: Colonic motility is crucial for the resolution of postoperative ileus.
      However, few data are available on postoperative colonic motility and no data on
      postoperative colonic tone. We aimed to characterize postoperative colonic tone
      and motility in patients. METHODS: Nineteen patients were investigated with
      combined barostat and manometry recordings after left colonic surgery. During
      surgery a combined recording catheter was placed in the colon with two barostat
      bags and four manometry channels cephalad to the anastomosis. Recordings were
      performed twice daily from Day 1 to Day 3 after surgery. RESULTS: Manometry
      showed an increasing colonic motility index, which was a mean (+/- standard error
      of the mean) of 37 +/- 5 mmHg/minute on Day 1, 87 +/- 19 mmHg/minute on Day 2,
      and 102 +/- 13 mmHg/minute on Day 3 (P < 0.05 for Day 1 vs. Day 2 and Day 2 vs.
      Day 3). Low barostat bag volumes indicating a high colonic tone were observed on
      Day 1 after surgery and increased subsequently (barostat bag I was 19 +/- 4, 32
      +/- 6, and 32 +/- 6 ml; barostat bag II was 13 +/- 1, 19 +/- 3, and 22 +/- 5 ml
      on Days 1, 2, and 3, respectively; for both barostat bags P < 0.05 for Day 1 vs.
      Day 2 but not Day 2 vs. Day 3). CONCLUSIONS: Colonic motility increased during
      the postoperative course. The low barostat bag volumes indicated a high colonic
      tone postoperatively which would correspond to a contracted rather than to a
      distended colon. High colonic tone postoperatively may be relevant for
      pharmacologic treatment of postoperative ileus.

PMID- 10910240
TI  - Repair of fistulas-in-ano using fibrin adhesive: long-term follow-up.
AB  - PURPOSE: Fibrin adhesive has been successfully used to treat fistulas-in-ano, but
      long-term data have been lacking. We report the results of our 18-month study
      examining the repair of fistulas-in-ano using autologous and commercial fibrin
      adhesive. METHODS: A 79-patient, prospective, non-randomized clinical trial was
      performed in which fibrin adhesive was used to repair fistulas-in-ano. Twenty-six
      patients were treated with autologous fibrin tissue adhesive made from their own
      blood, and 53 patients were treated with commercial fibrin sealant. In the
      operating room the patient underwent an examination under anesthesia, with an
      attempt to identify the primary and secondary fistula tract openings. The fistula
      tract was then curetted. Fibrin adhesive was injected into the secondary fistula
      tract opening until adhesive was seen coming from the primary opening. A
      petroleum jelly gauze was then applied over both the primary and secondary
      openings, and the patient was sent home. Follow-up visits occurred one week, one
      month, three months, and one year later. RESULTS: Fourteen of 26 (54 percent)
      patients treated with autologous fibrin tissue adhesive made from their own blood
      had complete closure of their fistulas after a one-year follow-up, whereas 34 of
      53 (64 percent) patients treated with commercial fibrin sealant had closure of
      their fistulas. Most treatment failures occurred within the first 3 months, but
      late failures were seen as far as 11 months postoperative. CONCLUSIONS: Fibrin
      tissue adhesive offers a unique mode of managing fistulas-in-ano, which is
      surgically less invasive, but recurrences up to one year later are being seen.
      Longer follow-up and further research is recommended for improvement.

PMID- 10910241
TI  - Prospective evaluation of omentoplasty in preventing leakage of colorectal
      anastomosis.
AB  - PURPOSE: The aim of this study was to investigate the role of omentoplasty, by
      means of intact omentum, in preventing anastomotic leakages after rectal
      resection. METHODS: Between 1992 and 1997 a total of 112 patients (64 males) with
      a mean age of 64.7 (range, 39-83) years were randomly assigned to undergo
      omentoplasty (Group A) or not (Group B) to reinforce the colorectal anastomosis
      after anterior resection for rectal cancer. The primary end point was anastomotic
      leakage; the secondary end point included morbidity and mortality related to
      omentoplasty. RESULTS: The two groups were comparable in terms of preoperative
      and intraoperative characteristics. Staple-ring disruption at plain abdominal
      radiographs was detected in seven instances in Group A and in ten in Group B
      patients (P = not significant). Two leakages were evident clinically in Group A
      and seven in Group B (P < 0.05). Three leaks were documented radiologically in
      Group A and eight in Group B (P = not significant). No complications related to
      omentoplasty were observed in Group A. There were two repeat operations for
      anastomotic leakage in Group B. At followup, one stricture developed in Group A
      and three in Group B (P = not significant) CONCLUSIONS: Despite a similar
      incidence of staple-ring defects, a strikingly lower rate of clinically and
      radiologically detected leaks developed in patients submitted to omentoplasty.
      Although not affecting the incidence of anastomotic disruption, omentoplasty
      seems to contain the severity of anastomotic leakage.

PMID- 10910242
TI  - New, simple approach for maximal pudendal nerve exposure: anomalies and prospects
      for functional reconstruction.
AB  - PURPOSE: Functional neosphincters after pudendal nerve anastomosis proved
      possible in animal models and may be applicable in humans, but access is a
      recognized problem. We report the occurrence of pudendal nerve anomalies, its
      implications for reconstruction, and describe a new approach for maximal
      exposure. METHODS: Adult human cadavers were positioned prone and dissected via a
      gluteal approach. Pudendal nerve variations and physical measurements were
      analyzed statistically. RESULTS: A new, simple, four-step approach (surface
      landmarks and exposure of gluteus maximus muscle, sacrotuberous ligament, and
      pudendal neurovascular bundle) permitted optimal pudendal nerve exposure in all
      14 human cadavers (28 limbs). Six were males and had a mean age of 82 (range, 58
      102) years. Two anomalies, Type 1 (2-trunked) and Type 2 (3-trunked), of the
      pudendal nerve were recognized in 30 percent of cadavers, with a left-to-right
      ratio of 2.5:1. Mean pudendal nerve length over the ischial spine was 23.9
      (range, 19-28) mm right, 24.2 (range, 19-28) mm left (P = 0.54), but its diameter
      measured 5.2 mm (right) and 4.9 mm (left; P = 0.04). Mean length of pudendal
      nerve trunk exposed after reflection of the sacrotuberous ligament was 55 (range,
      44-75) mm on either side before division into terminal branches. The number and
      percent frequency of inferior rectal nerve on both sides were 1 (13 percent), 2
      (76 percent), and 3 (11 percent), respectively, with a mean length of 27.1
      (range, 21-34) mm right and 27.9 (range, 20-33) mm left (P = 0.31). CONCLUSION: A
      simple four-step approach to the pudendal nerve contributes to improved access in
      all cases. It facilitates reconstruction because it allows accurate nerve
      selection and recognition of potential anomalies that might influence functional
      outcome.

PMID- 10910243
TI  - Randomized trial of fecal diversion for sphincter repair.
AB  - PURPOSE: Fecal diversion for sphincter repair is controversial. This randomized
      trial assessed whether fecal diversion would improve primary wound healing and
      functional outcome after sphincter repair. METHODS: Thirty-three patients with
      fecal incontinence requiring sphincter repair were recruited, but only 27 agreed
      to be randomly assigned to a defunctioning stoma (n = 13) or no stoma (n = 14).
      Patients were assessed by the Cleveland Clinic Incontinence Score (0-20) and anal
      physiology; the mean follow-up was 34 (range, 16-47) months. RESULTS:
      Incontinence score improved significantly in both groups (stoma, 13.5-7.8; P =
      0.0072; no stoma, 14-9.6; P = 0.0470): No difference was found between the two
      groups. Maximum resting pressure and maximum squeeze pressure increased
      significantly only in the no-stoma group (maximum resting pressure, 52.4-71.3 cm
      H2O; maximum squeeze pressure, 87.3-100.7 cm H2O; P < 0.0001). There was no
      significant difference in functional outcome (stoma, 7.8; no stoma, 9.6; P =
      0.4567) or the number with complications of sphincter repair (stoma, 5; no stoma,
      3; P = 0.4197). However, stoma-related complications occurred in 7 of 13 patients
      having a stoma (parastomal hernia, 2; prolapsed stoma, 1; incisional hernia at
      the stoma site requiring repair, 5; and wound infection at the closure site, 1).
      CONCLUSION: Fecal diversion in sphincter repair is unnecessary, because it gives
      no benefit in terms of wound healing or functional outcome, and it is a source of
      morbidity.

PMID- 10910245
TI  - Prognostic influence of p53 nuclear overexpression in colorectal carcinoma.
AB  - PURPOSE: The aim of this study was to test the prognostic influence of p53
      nuclear overexpression in colorectal carcinoma. METHODS: We performed an analysis
      of the prognostic influence of the nuclear overexpression of p53 with
      immunohistochemistry in 126 cases of colorectal carcinoma operated on in our
      hospital between 1987 and 1992, with a minimum follow-up time of 60 months (5
      years). RESULTS: Our results show a statistically significant prognostic
      influence of p53 overexpression on disease-free survival time, but not on the
      overall survival time, in univariate analysis, but this influence is lost in
      multivariate analysis. CONCLUSIONS: Our results confirm recent reports by other
      authors that failed to show the independent prognostic value of p53 in colorectal
      carcinoma.

PMID- 10910244
TI  - Variations in motor evoked potential latencies in the anal sphincter system with
      sacral magnetic stimulation.
AB  - PURPOSE: The anal sphincter system of the skeletal musculature consists of
      various parts but functions as a single unit. The motor latencies measured at the
      puborectalis, deep external anal sphincter, superficial external anal sphincter,
      and subcutaneous external anal sphincter have yet to be clearly elucidated. This
      study was designed to measure the motor latencies of these sphincters separately
      and to investigate the electrophysiologic heterogeneity of the anal sphincter
      system. METHODS: In 20 preoperative patients with colon cancer without either
      neurologic or anorectal diseases, motor evoked potentials were taken separately
      bilaterally at levels measuring approximately 5, 3.8, 2.6, and 1.5 cm from the
      perineal skin using a concentric needle electrode after magnetic stimulation on
      the sacral region. These latencies were considered to be separately measured at
      the puborectalis, deep, superficial, and subcutaneous external anal sphincter.
      RESULTS: The motor latencies (median (95 percent confidence interval)) were 4.33
      (4.1-4.93; right) and 4.24 (3.97-5.22; left) ms at the 5 cm level; 5.96 (5.45
      7.32; right) and 6.44 (5.49-8.20; left) ms at the 3.8 cm level; 9.28 (7.99-11.21;
      right) and 8.88 (7.68-10.93; left) ms at the 2.6 cm level; and 11.06 (9.69-14.13;
      right) and 9.18 (8.09-10.31; left) ms at the 1.5 cm level. Significant
      differences were seen in the latencies between the 5 cm level and the other
      levels and between the 3.8 cm level and the other levels. CONCLUSIONS: The motor
      latencies in the anal sphincter system significantly varied depending on the
      distance from the skin. The latency may be shortest in the puborectalis and
      increasingly longer in the deep, superficial, and subcutaneous EAS, in that
      order.

PMID- 10910247
TI  - Angiogenesis of liver metastases: role of sinusoidal endothelial cells.
AB  - PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of
      endothelial cells derived from pre-existing blood vessels. Vascular endothelial
      growth factor is the growth factor most closely implicated in the development of
      neovessels in colon cancer. However, vascular endothelial growth factor-specific
      receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels
      surrounding vascular endothelial growth factor-producing secondary hepatic
      tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism
      of neovessel formation within liver metastatic carcinomas remains unclear. The
      purpose of this study was to determine whether sinusoidal endothelial cells are
      involved in tumor angiogenesis in a syngeneic model of liver metastases from
      colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by
      fluorescence microscopy after uptake of acetylated low density lipoprotein
      labeled with a fluorescent probe (dioctadecylindocarbocyanine). One hundred
      microliters of dioctadecylindocarbocyanine acetylated low density lipoprotein
      were injected intraportally at the start of experiment in BD IX rats. Two days
      later, intraportal injection of 10(7) DHD K12, a chemically induced colon
      carcinoma cell line, was performed in syngeneic BD IX rats. Animals were killed
      one week later and the livers were processed for routine histologic examination
      and immunohistochemistry using the rat endothelial cell antigen-1 monoclonal
      antibody. RESULTS: In normal parenchyma fluorescence was associated with
      sinusoidal cells but not with endothelium of large blood vessels. Thus, specific
      acetylated low density lipoprotein uptake allowed histological differentiation of
      sinusoidal endothelial cells from other large-vessel endothelial cells present in
      the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence
      was generated. Labeled cells accumulated at the periphery of the metastases. When
      tumors grow beyond 200 microm, neovessel formation was observed; there was an
      invasion of fluorescent-labeled cells from the periphery, which were arranged in
      a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor
      vessels are lined with sinusoidal endothelial cells. Identification of a specific
      cell type involved in the formation of the stromal compartment of tumors has
      important implications. Sinusoidal endothelial cells express well-characterized
      surface receptors and differ morphologically and metabolically from large-vessel
      endothelia. They should be considered as attractive targets for future and
      existing antiangiogenic strategies directed against the stromal compartment of
      liver metastases.

PMID- 10910246
TI  - The natural history of isolated rectosigmoid adenomatous polyps: is flexible
      sigmoidoscopy a safe alternative for surveillance?
AB  - PURPOSE: Colonoscopic surveillance is recommended for patients with adenomatous
      polyps. Significant cost savings would result from identification of subgroups of
      patients in whom less costly surveillance would suffice. This study was performed
      to determine the natural history of patients undergoing removal of isolated
      rectosigmoid adenomas and to establish whether flexible sigmoidoscopy might be
      adequate for follow-up. METHODS: A retrospective review of a database of 7,677
      colonoscopies, from 1990 to 1996, identified patients who had a minimal follow-up
      of two years after removal of adenomatous polyps isolated to the rectosigmoid.
      Polyps detected on surveillance colonoscopy were categorized as distal (< or =60
      cm from anal verge), proximal (>60 cm from anal verge), and diffuse (proximal
      plus distal). The risk of polyp formation was determined by actuarial analysis
      using the Kaplan-Meier method. RESULTS: Sixty-two patients undergoing
      surveillance for adenomas met inclusion criteria. At the index colonoscopy, 124
      isolated rectosigmoid polyps were identified. The median polyp size was 1 cm and
      median frequency was one polyp. The median follow-up time for the entire cohort
      (N = 62) was 53 months. At follow-up surveillance colonoscopy, 105 additional
      adenomas were discovered and removed in 40 patients. No malignant polyps were
      detected. The pattern of polyps detected were proximal (n = 19), rectosigmoid (n
      = 16), and diffuse (n = 5). CONCLUSIONS: The majority (65 percent) of patients
      with isolated rectosigmoid polyps have additional polyps on long-term
      surveillance, and 60 percent of patients will have these polyps located proximal
      to the reach of a sigmoidoscope. Therefore, flexible sigmoidoscopy is not a safe
      alternative for surveillance of patients with isolated rectosigmoid polyps.

PMID- 10910248
TI  - Effect of pedunculated seromuscular flap on bursting strength of intestinal
      anastomosis after corticosteroid treatment.
AB  - PURPOSE: This study was designed to investigate the protective effect of a
      pedunculated seromuscular flap on intestinal anastomosis after corticosteroid
      treatment. METHODS: Forty male Sprague-Dawley rats were divided into four groups,
      and all animals underwent intestinal anastomosis. Two groups, with or without
      seromuscular flap wrapping, received 5 mg cortisone acetate, and two groups
      received placebo (saline) preoperatively for 16 days. Anastomotic strength was
      defined as bursting pressure (in millimeters of mercury). The pedunculated
      seromuscular flap was prepared from a segment of intestine next to the
      anastomosis. Intestinal bursting strength at the anastomotic site was measured at
      Postoperative Day 8. RESULTS: The anastomotic bursting strength was significantly
      lower in the steroid groups at Postoperative Day 8 (P < 0.01). The pedunculated
      seromuscular flap increased the strength of the anastomosis both in the steroid
      and control groups (P < 0.05). CONCLUSION: The adverse effect of corticosteroids
      on intestinal anastomoses may be prevented by a pedunculated seromuscular flap.

PMID- 10910249
TI  - Use of accurate diagnostic criteria may increase incidence of stercoral
      perforation of the colon.
AB  - PURPOSE: Stercoral perforation of the colon is reported to be a rare disease with
      poor prognosis. The aim of this study was to determine the frequency of stercoral
      perforation of the colon, to define diagnostic criteria for stercoral perforation
      of the colon, and to analyze the patient outcome in a university hospital
      gastrointestinal surgery unit. METHODS: From November 1993 until November 1998
      all surgically treated patients with a colorectal disease were prospectively
      recorded in a computerized database. Diagnosis of stercoral perforation of the
      colon was made if 1) the colonic perforation was round or ovoid, exceeded 1 cm in
      diameter, and lay antimesenteric; 2) fecalomas were present within the colon,
      protruding through the perforation site or lying within the abdominal cavity; and
      3) pressure necrosis or ulcer and chronic inflammatory reaction around the
      perforation site were present microscopically. Any additional colon pathology led
      to exclusion from the diagnosis of stercoral perforation of the colon. Using the
      same criteria, 81 cases in the literature were found to qualify and were further
      analyzed. RESULTS: In a five-year period 1,295 patients underwent colorectal
      interventions through laparotomy. A total of 566 (44 percent) cases were
      emergencies, 220 (17 percent) of these caused by colonic perforation. Seven
      patients had stercoral perforation of the colon. The incidence of stercoral
      perforation of the colon was 0.5 percent of all surgical colorectal procedures
      through laparotomy, 1.2 percent of all emergency colorectal procedures, and 3.2
      percent of all colonic perforations. The mean age of the patients was 59 (median,
      64; range, 22-85) years. All perforations were situated in the left hemicolon or
      upper rectum. The round or ovoid perforation had a mean diameter of 3.6 cm.
      Fecalomas were present in all patients and protruded from the perforation site or
      were found within the free abdominal cavity in three of them. Generalized
      stercoral peritonitis was a constant finding. Using a colonic resection without
      immediate restoration of continuity, an extensive intraoperative lavage, and
      antibiotics, there was no in-hospital mortality. Analysis of the reports in the
      literature revealed additionally that 28 percent of patients with stercoral
      perforation of the colon have multiple stercoral ulcers in the colon and that
      substantial mortality is encountered if only minor surgical procedures of
      treatment are used. CONCLUSIONS: The incidence of stercoral perforation of the
      colon seemed to have been underestimated. The reason for this might be the lack
      of defined diagnostic criteria for this disease. Low mortality is obtained by
      early surgical eradication of the affected part of the colon, including all
      stercoral ulcers, and by aggressive therapy for peritonitis.

PMID- 10910250
TI  - Antineutrophil cytoplasmic antibodies in inflammatory bowel disease: clinical
      role and review of the literature.
AB  - PURPOSE: Perinuclear antineutrophil cytoplasmic antibodies have been found
      consistently in patients with ulcerative colitis; however, their pathogenetic and
      clinical role is still uncertain. In this study we tested the prevalence of
      perinuclear antineutrophil cytoplasmic antibodies in a large population of
      patients with ulcerative colitis and Crohn's disease, with particular attention
      to the possible correlation with clinical features. METHODS: Perinuclear
      antineutrophil cytoplasmic antibody reactivity was investigated with indirect
      immunofluorescence in 279 patients with ulcerative colitis, 110 patients with
      Crohn's disease, and 252 unrelated healthy subjects. RESULTS: Perinuclear
      antineutrophil cytoplasmic antibodies were found in 84 of 279 patients with
      ulcerative colitis (30 percent), 10 of 110 patients with Crohn's disease (9
      percent), and 2 of 252 healthy subjects (<1 percent; P < 0.001), respectively.
      Perinuclear antineutrophil cytoplasmic antibodies were significantly more
      frequent in patients with ulcerative colitis with higher relapse rate (43 vs. 27
      percent; P < 0.002), and patients with Crohn's disease with colitis (27 vs. 2.5
      percent; P < 0.0003). Perinuclear antineutrophil cytoplasmic antibodies were also
      significantly less frequent in patients with ulcerative colitis in remission (18
      vs. 34 percent; P < 0.0025). CONCLUSIONS: In this study we confirm the relative
      specificity of perinuclear antineutrophil cytoplasmic antibodies, either for
      ulcerative colitis or for Crohn's disease involving the colon. Perinuclear
      antineutrophil cytoplasmic antibodies were more frequently found in patients with
      ulcerative colitis with a more aggressive clinical behavior; however, their
      presence had a limited value in identifying homogeneous subgroups of patients in
      our population.

PMID- 10910251
TI  - Proposed association between ileoanal j-pouch perforation and rapid consumption
      of a high-calorie, high-fiber meal: report of two cases.
AB  - PURPOSE: We report two cases of ileoanal J-pouch rupture after rapid consumption
      of high-fiber, high-calorie meals. METHOD: We review the food intake,
      presentation, laboratory and radiographic data, and course of two patients who
      developed ileoanal J-pouch perforation after rapid consumption of meals rich in
      fiber or calories or both. The potential association between food consumption and
      rupture is explored. RESULTS: The authors propose that the rapid ingestion of a
      high-fiber, high-calorie meal may lead to an acute intraluminal pressure
      elevation or a closed-loop obstruction. These effects may be the basis for an
      association between food ingestion patterns and perforation at the distal
      transection site in an ileoanal J-pouch. CONCLUSION: The authors hypothesize that
      the rapid ingestion of a high-fiber, high-calorie meal may be associated with J
      pouch perforation. Further investigative efforts are needed to confirm this
      association and to evaluate whether a causal relationship is present. If
      causality is established, physicians may develop a higher index of suspicion for
      pouch rupture in patients who present with abdominal disturbances after the rapid
      ingestion of a high-fiber, high-calorie meal.

PMID- 10910252
TI  - Familial adenomatous polyposis complicated by an intrahepatic desmoid tumor:
      report of a case.
AB  - Desmoids are uncommon proliferations of fibroblasts that occur with
      disproportionate frequency in patients with familial adenomatous polyposis. They
      do not metastasize and are histologically benign. Despite this, the unpredictable
      and often aggressive nature of familial adenomatous polyposis-associated desmoids
      and their tendency to occur in intra-abdominal sites means that they present a
      difficult management problem, and they are a leading cause of death in patients
      with familial adenomatous polyposis who have undergone colectomy. We report a
      case of a patient with familial adenomatous polyposis who had extensive and
      aggressive desmoid disease and whose management was further complicated by a
      large intrahepatic desmoid. There are no previous reports of desmoids occurring
      in the liver.

PMID- 10910253
TI  - Lumbar osteomyelitis and epidural abscess complicating recurrent pilonidal cyst:
      report of a case.
AB  - PURPOSE: This study was conducted to report the rare presentation of lumbar
      osteomyelitis and epidural abscess as a complication of a pilonidal cyst.
      METHODS: A case report is presented. RESULTS: We describe the rare case of a male
      patient with diabetes with a recurring pilonidal cyst who developed a lumbar
      osteomyelitis and epidural abscess three weeks after pilonidal cyst excision with
      epidural anesthesia, with a fatal outcome despite emergency treatment.
      CONCLUSIONS: Life-threatening complications should be kept in mind in high-risk
      patients with repetitive surgery and neurologic involvement.

PMID- 10910254
TI  - How to remove an impacted chicken bone from the sigmoid colon endoscopically.
AB  - A technique for endoscopic removal of a chicken bone impacted in the sigmoid
      colon is described. Using biopsy forceps, a silk tie was looped around the
      impacted bone and then gently pulled caudally as it exited the anus. This
      disimpacted the bone. There were no complications.

PMID- 10910255
TI  - Modification of the gluteal perforator-based flap for reconstruction of the
      posterior vagina.
AB  - Vaginal reconstruction after pelvic exenteration not only affords significant
      psychological benefit, it also decreases the morbidity and mortality associated
      with pelvic exenteration. In irradiated patients filling the surgical defect with
      healthy, well-vascularized tissue, such as omental flaps, colonic advancements,
      and myocutaneous flaps, has been shown to decrease the incidence of fistulas,
      bowel obstructions, infections, and hemorrhage. A novel use of the gluteal
      perforator-based flap is described in the unique circumstance of posterior pelvic
      exenteration with sacrectomy.

PMID- 10910256
TI  - Mechanisms of nephrotoxicity.

PMID- 10910257
TI  - Histopathology of calcineurin inhibitor-induced nephrotoxicity.

PMID- 10910258
TI  - The clinical impact of nephrotoxicity in renal transplantation.

PMID- 10910259
TI  - The clinical impact of nephrotoxicity in liver transplantation.

PMID- 10910260
TI  - The clinical impact of cyclosporine nephrotoxicity in heart transplantation.

PMID- 10910261
TI  - Is nonnephrotoxic immunosuppression a possibility?

PMID- 10910262
TI  - Management strategies for nephrotoxicity.

PMID- 10910263
TI  - Extracellular matrix proteins in organ transplantation.

PMID- 10910264
TI  - Encephalitis caused by human herpesvirus-6 in transplant recipients: relevance of
      a novel neurotropic virus.
AB  - BACKGROUND: Human herpesvirus-6 (HHV-6) is a neurotropic virus. Encephalitis is a
      significant clinical manifestation of HHV-6; however, sparse data on this entity
      exist in transplant recipients. METHODS: Cases of HHV-6 encephalitis reported in
      the literature (13 bone marrow transplant recipients and 1 liver transplant
      recipient) were reviewed. The diagnosis was established in all by viral isolation
      and/or detection of HHV-6 DNA in the cerebrospinal fluid by polymerase chain
      reaction or histopathologic method. RESULTS: HHV-6 encephalitis occurred a median
      of 45 days (range 10 days to 15 months) after transplantation. Mental status
      changes, ranging from confusion to coma (92%), seizures (25%), and headache (25%)
      were the predominant clinical presentations. Focal neurologic findings occurred
      in only 17% of the patients. Twenty-five percent of the patients had fever;
      however, the height of fever (< or =40 degrees C) in febrile patients was
      striking. Cerebrospinal fluid pleocytosis was generally lacking. Abnormal
      neuroimaging findings, characterized by low-attenuation lesions in the posterior
      cerebral lobes, were present only in 17% of the patients. Overall mortality in
      patients with HHV-6 encephalitis was 58% (7 of 12); 42% (5 of 12) of the deaths
      were caused by HHV-6. Cure was documented in 7 of 8 patients who received
      ganciclovir or foscarnet for > or =7 days, compared with 0% (0 of 4) in those who
      did not receive these drugs or received them for < 7 days (P=.01). CONCLUSIONS:
      HHV-6 may be associated with encephalitis after transplantation and warrants
      consideration in transplant recipients with encephalitis of unidentifiable
      etiology.

PMID- 10910265
TI  - The role of IL-2 in allograft rejection--a lesson learned from experimental work.

PMID- 10910266
TI  - Mixed bone marrow chimerism across discordant xenogeneic barriers: the solution
      for inducing xenotransplant tolerance?

PMID- 10910267
TI  - Porcine stem cell engraftment and seeding of murine thymus with class II+ cells
      in mice expressing porcine cytokines: toward tolerance induction across
      discordant xenogeneic barriers.
AB  - BACKGROUND: Mixed hematopoietic chimerism is a reliable means of tolerance
      induction, but its utility has not been demonstrated in discordant xenogeneic
      combinations because of the difficulty in achieving lasting hematopoietic
      engraftment. Miniature swine are likely to be suitable organ donors for humans.
      To evaluate the ability of mixed chimerism to induce swine-specific tolerance in
      widely disparate xenogeneic recipients, this study aimed to achieve long-lasting
      chimerism in a pig to mouse combination. METHODS: Immunodeficient transgenic mice
      were developed by crossing transgenic founders carrying porcine interleukin-3,
      granulocyte macrophage-colony stimulating factor, and stem cell factor genes with
      severe combined immunodeficient mice or non-obese diabetic/severe combined
      immunodeficient mice. Swine bone marrow transplantation was performed in these
      mice, and porcine chimerism was followed for 20 weeks. RESULTS: Whereas swine
      cells became undetectable in all non-Tg littermates by 7 weeks, high levels of
      porcine hematopoietic chimerism, including the presence of porcine class II+
      cells in the host thymus were maintained in Tg mice for >20 weeks. Colony-forming
      assays revealed the presence of large numbers of swine hematopoietic progenitor
      cells in the marrow of these mice at 20 weeks after bone marrow transplantation.
      CONCLUSIONS: These transgenic mice demonstrate for the first time that
      spontaneous migration of marrow donor antigen-presenting cells to an intact
      recipient thymus can occur and that porcine stem cells can persist in this highly
      disparate species combination. These data therefore support the feasibility of
      the eventual goal of tolerance induction by mixed chimerism in discordant
      xenogeneic combinations.

PMID- 10910268
TI  - Transplantation of the bone marrow microenvironment leads to hematopoietic
      chimerism without cytoreductive conditioning.
AB  - BACKGROUND: It has been hypothesized that regimens to induce transplantation
      tolerance and long-term hematopoietic chimerism require recipient conditioning
      with whole body irradiation or a cytoablative regimen to create space within the
      marrow microenvironment to permit pluripotent stem cell engraftment. The purpose
      of this study was to determine if transplantation of an intact bone marrow
      microenvironment in the form of a bone graft would permit stable hematopoietic
      stem cell engraftment, shape the repertoire of developing T cells, and induce
      donor-specific unresponsiveness in the absence of a conditioning regimen.
      METHODS: Fragments of femur were transplanted under the kidney capsule of
      recipient mice. At defined time points after bone graft transplantation
      recipients were assayed for chimerism, bone graft viability, and responses to
      donor and third party alloantigens in vitro and in vivo. RESULTS: In the absence
      of an immunological barrier, bone graft transplantation resulted in long-term
      multi-lineage hematopoietic chimerism in the peripheral blood. Nude bone graft
      transplantation into SCID recipients resulted in development of donor- derived T
      cells that underwent negative selection on bone graft derived I-E+ cells within
      the thymus. Across a fully allogeneic barrier in immunocompetent recipients
      treated with combined blockade of the CD40 and CD28 pathways bone graft
      transplantation resulted in long-term donor-specific hyporesponsiveness in vitro
      and acceptance of donor specific skin grafts. CONCLUSIONS: Transplantation of
      bone marrow in the form of a bone graft may facilitate the production of
      hematopoietic chimerism and lead to long-term donor-specific hyporesponsiveness
      in the absence of a cytoreductive conditioning regimen.

PMID- 10910269
TI  - Durable donor-specific T and B cell tolerance in rhesus macaques induced with
      peritransplantation anti-CD3 immunotoxin and deoxyspergualin: absence of chronic
      allograft nephropathy.
AB  - Tolerance induction can prevent acute kidney allograft rejection without chronic
      immunosuppression. It is uncertain whether specific tolerance can prevent chronic
      allograft nephropathy (CAN), which involves both nonimmune and immune injury.
      This report provides evidence that immunologically tolerant macaques, induced
      with immunotoxin and deoxyspergualin, developed neither acute rejection nor CAN.
      Long survivors, bearing MHC-mismatched grafts without chronic immunosuppression
      for 0.8 to 3.4 years, exhibited general immune competence with donor-specific T
      and B cell tolerance and no functional or histological evidence of CAN. Stringent
      criteria for tolerance were satisfied by specific prolongation of donor skin
      grafts with rapid rejection of third-party skin, followed by indefinite
      acceptance of a second donor kidney graft and establishment of microchimerism.
      Primate tolerance with documented absence of CAN may give impetus to the clinical
      application of tolerance.

PMID- 10910270
TI  - Renal xenografts from triple-transgenic pigs are not hyperacutely rejected but
      cause coagulopathy in non-immunosuppressed baboons.
AB  - BACKGROUND: The genetic modification of pigs is a powerful strategy that may
      ultimately enable successful xenotransplantation of porcine organs into humans.
      METHODS: Transgenic pigs were produced by microinjection of gene constructs for
      human complement regulatory proteins CD55 and CD59 and the enzyme alpha1,2
      fucosyltransferase (H-transferase, HT), which reduces expression of the major
      xenoepitope galactose-alpha1,3-galactose (alphaGal). Kidneys from CD55/HT and
      CD55/CD59/HT transgenic pigs were transplanted into nephrectomised,
      nonimmunosuppressed adult baboons. RESULTS: In several lines of transgenic pigs,
      CD55 and CD59 were expressed strongly in all tissues examined, whereas HT
      expression was relatively weak and did not significantly reduce alphaGal. Control
      nontransgenic kidneys (n=4) grafted into baboons were hyperacutely rejected
      within 1 hr. In contrast, kidneys from CD55/HT pigs (n=2) were rejected after 30
      hr, although kidneys from CD55/CD59/HT pigs (n=6) maintained function for up to 5
      days. In the latter grafts, infiltration by macrophages, T cells, and B cells was
      observed at days 3 and 5 posttransplantation. The recipients developed
      thrombocytopenia and abnormalities in coagulation, manifested in increased
      clotting times and an elevation in the plasma level of the fibrin degradation
      product D-dimer, within 2 days of transplantation. Treatment with low molecular
      weight heparin prevented profound thrombocytopenia but not the other aspects of
      coagulopathy. CONCLUSIONS: Strong expression of CD55 and CD59 completely
      protected porcine kidneys from hyperacute rejection and allowed a detailed
      analysis of xenograft rejection in the absence of immunosuppression. Coagulopathy
      appears to be a common feature of pig-to-baboon renal transplantation and
      represents yet another major barrier to its clinical application.

PMID- 10910271
TI  - Early and late chemokine production correlates with cellular recruitment in
      cardiac allograft vasculopathy.
AB  - BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of
      late mortality in heart transplant recipients. Activated T lymphocytes and
      macrophages infiltrate the donor heart before vascular intimal thickening
      develops, but the specific mediators of mononuclear cell recruitment leading to
      CAV are unknown. Therefore, we sought to define the relationship between
      chemokine gene expression and production, T lymphocyte and macrophage
      recruitment, and intimal thickening in a murine model of CAV. METHODS: B10.A or
      B10.BR strain hearts were transplanted heterotopically into B10.BR mice.
      Recipients were killed at 1, 4, 7, 14, and 30 days. Donor hearts were assayed for
      chemokine gene expression with ribonuclease protection and for protein with
      ELISA. Intragraft cellular infiltration was defined immunohistochemically.
      Intimal thickening was quantitated morphometrically. RESULTS: Early and late
      patterns of intragraft chemokine expression associated with distinct cellular
      infiltration were identified. First, transient MIP-2 and MCP-1/JE production in
      isografts and allografts correlated with neutrophil and macrophage infiltration.
      MCP-1/JE production and macrophage infiltration was greater in allografts than
      isografts. Second, allografts demonstrated sustained lymphotactin, RANTES, and IP
      10 expression, beginning at day 4, correlating with persistent macrophage and T
      lymphocyte infiltration. Intimal thickening became evident at 14 days. Isografts
      did not display the late pattern of sustained chemokine gene expression, cellular
      infiltration, or intimal thickening. CONCLUSIONS: Transient, early MIP-2, and MCP
      1/JE production in isografts and allografts correlated with neutrophil and
      macrophage recruitment, and is likely related to ischemia-reperfusion. In
      allografts, the delayed induction of chemokines specific for macrophages and T
      lymphocytes correlated with mononuclear cell infiltration and preceded intimal
      thickening. This study thus demonstrates a dual pattern of chemokine induction
      correlating with intragraft mononuclear cell recruitment, associated with
      ischemia-reperfusion and CAV development. Chemokine-directed interventions may
      interfere with leukocyte trafficking and inhibit CAV development.

PMID- 10910272
TI  - Prevention of graft vessel disease by combined FTY720/cyclosporine. A treatment
      in a rat carotid artery transplantation model.
AB  - BACKGROUND: Graft vessel disease (GVD) is an important problem often responsible
      for late graft loss. The effects of FTY720, an immunomodulator with a novel
      mechanism of action were investigated in combination with cyclosporine A (CsA) in
      a carotid artery allograft model. METHODS: A segment of the carotid artery of
      Lewis rats was replaced by a DA allograft. Seven groups of eight rats were
      treated for 8 weeks with vehicle (P), CsA 0.3 (C0.3), 1 (C1) or 3 (C3) mg x kg(
      1).day(-1) or a combination of CsA 1 with FTY 0.01 (C1F0.01), 0.03 (C1F0.03), and
      0.1 (C1F0.1) mg x kg(-1).day(-1). Lumen area was estimated by magnetic resonance
      imaging, peripheral lymphocyte count and drug concentrations were determined at 1
      and 8 weeks. Neointima, media, and lumen area were measured morphometrically.
      Intimal and adventitial infiltration of mononuclear cells, and medial smooth
      muscle cells number was assessed using a score. RESULTS: FTY720 did not influence
      CsA blood concentrations. FTY720 but not CsA decreased the PLC dose dependently.
      Magnetic resonance imaging revealed that treatment groups have larger lumen size
      than group P. Histological and morphometric evaluation showed that all aspects of
      GVD were dose dependently suppressed by treatment and lumen narrowing was
      prevented. CONCLUSIONS: CsA, at clinically relevant blood levels, suppressed GVD
      only partly. The addition of FTY720 was well tolerated and completely suppressed
      GVD development. In vivo lumen size did not correlate with the histologically
      estimated neointimal thickness.

PMID- 10910273
TI  - Prior induction of heat shock proteins by a nitric oxide donor attenuates cardiac
      ischemia/reperfusion injury in the rat.
AB  - BACKGROUND: Recent studies have demonstrated that nitric oxide (NO) releasers
      considerably increase heat shock proteins (HSPs) in the in vitro cell system,
      providing resistance to oxidant damage. This study was designed to examine the
      cellular responses of HSPs induced by prior administration of an NO releaser,
      FK409 (FK), in an in vivo transplantation model. METHODS: Lewis rats received
      either saline or FK solution intravenously administered at different time points
      before graft harvesting (10 micromol/kg) or for 15 min during reperfusion (0.66
      micromol/kg/min). Tissue specimens were taken to determine HSP70 and heme
      oxygenase-1/HSP32 (HO-1) expression, and glutathione content. After 24-hr
      preservation with University of Wisconsin solution, heterotopic cardiac
      transplantations were performed, and graft survival was determined at 14 days.
      Tissue samples for end labeling of nuclear DNA fragments (TdT-mediated d-uridine
      triphosphate biotin nick end labeling; TUNEL) and propidium iodide staining were
      taken 15 min after reperfusion. RESULTS: The gene and protein expression of HSP70
      after FK administration peaked at 12 min and 60-90 min, whereas those of HO-1
      peaked at 6 min and 90 min, respectively. Then, representative cardiac grafts
      taken 60 min after FK treatment were examined for further assay. Localization of
      induced HSP70 and HO-1 molecules were observed in the myocardium and vascular
      endothelium, respectively. Prior treatment of FK was effective in preventing the
      reduction of tissue glutathione contents compared with control (P<0.05). Fewer
      TUNEL and propidium iodide-positive cells were also observed in the FK group
      (P<0.0005, vs. control). The graft survival rate was higher in the FK group (9/10
      vs. 1/10 of control; P<0.001), whereas the groups either harvested 10 min after
      FK pretreatment or continuously infused for 15 min during reperfusion were
      inferior, similar to that of control. CONCLUSION: Prior induction of HSP70 and HO
      1 with a relatively low dose of FK administration attenuates ischemia and
      reperfusion injury, which was due to antioxidant and antiapoptotic activities
      augmented by such stress proteins. Thus, NO releasers as a pharmacological
      maneuver may provide an innovative approach for the prevention of ischemia and
      reperfusion injury.

PMID- 10910274
TI  - Co-transplantation of donor-derived hepatocytes induces long-term tolerance to
      cardiac allografts in a rat model.
AB  - BACKGROUND: Liver allografts transplanted between MHC-disparate mice, rats, and
      swine are spontaneously accepted in most strain combinations without requirement
      for immunosuppression. The underlying mechanism has, however, remained elusive.
      Here, we demonstrate that co-transplantation of donor-derived hepatocytes protect
      Lewis (RT1.A1) cardiac allografts from acute and chronic rejection in DA (RT1.Aa)
      recipients indefinitely. METHODS: Livers of donor Lewis rats were harvested and
      the hepatocytes separated from hepatic leukocytes by collagenase digestion and
      gradient separation. DA recipient animals were transplanted Lewis cardiac
      allografts and simultaneously intraportally infused either Lewis-derived
      hepatocytes or hepatic leukocytes. Recipient animals were either not further
      treated or received a single dose of 15 mg/kg cyclosporine. RESULTS: Donor
      hepatocytes alone significantly protected syngeneic cardiac allografts from
      rejection, whereas hepatic leukocytes failed to influence graft survival. In
      combination with cyclosporine, recipient cardiac allografts were indefinitely
      protected from rejection. Graft-infiltrating cells in tolerant animals presented
      as clusters of CD4+ T cells and stained mostly positive for interleukin-4,
      whereas graft-infiltrating cells in rejected allografts were predominantly
      positive for interferon-gamma. Adoptive transfer of splenocytes derived from
      tolerant animals protected Lewis cardiac allografts from rejection in DA
      recipients without immunosuppression. In contrast, hepatic leukocytes protected
      only 50% of the allografts from rejection. CONCLUSION: We propose that donor
      hepatocytes induce permanent engraftment of syngeneic allografts by establishing
      a Th2 type alloresponse that is transferable to new graft recipients. The results
      of this study demonstrate that liver parenchymal cells significantly mediate
      spontaneously liver-induced tolerance.

PMID- 10910275
TI  - Increased accuracy of renal allograft rejection diagnosis using combined
      perforin, granzyme B, and Fas ligand fine-needle aspiration immunocytology.
AB  - BACKGROUND: Two major routes by which cytotoxic T lymphocytes induce apoptosis in
      target cells are the perforin-granzyme and the Fas ligand/Fas pathways.
      Intragraft expression of message for these immune activation genes has been shown
      to correlate very closely with clinical rejection. We have immunolabeled fine
      needle aspiration biopsy samples using a panel of cytotoxic T-cell activation
      markers to evaluate the immunocytochemical identification of the protein products
      of these genes in the verification of human renal allograft rejection. METHODS:
      In this retrospective pilot study, 140 fine-needle aspiration biopsy samples from
      50 human renal allografts were labeled using alkaline phosphatase/ anti-alkaline
      phosphatase immunocytochemistry incorporating monoclonal antibodies to perforin,
      granzyme B, and Fas ligand. Levels of positive labeling for these markers were
      compared with the original clinical diagnosis of rejection. RESULTS: An excellent
      correlation with clinical rejection was obtained when all three antibodies were
      positive. The false positive rate for each antibody was sufficient to make any
      one alone or in combination with one other unreliable for diagnosing rejection.
      When all three antibodies gave positive labeling, agreement with clinical
      rejection status was superior to using conventional morphological cytology.
      CONCLUSIONS: In addition to providing valuable morphological information
      regarding the composition of inflammatory leukocyte populations and the
      preservation status of renal parenchymal cells, fine-needle aspiration biopsy
      samples may be labeled using combined perforin, granzyme B, and Fas ligand
      immunocytochemistry to offer a safe and reliable method for diagnosing rejection
      with an excellent level of accuracy.

PMID- 10910276
TI  - mRNA expression of intercellular adhesion molecule-1 and vascular cell adhesion
      molecule-1 in acute renal allograft rejection.
AB  - BACKGROUND: The intercellular adhesion molecule-1 (ICAM-1) and the vascular cell
      adhesion molecule-1 (VCAM-1) show a form of complementary distribution in normal
      and grafted kidneys. The molecular mechanism by which ICAM-1 and VCAM-1 are
      increased or induced on vascular cells during acute renal allograft rejection has
      not been clearly defined. METHODS: We examined ICAM-1 and VCAM-1 mRNA expression
      in 17 renal allograft biopsies with (n=12) and without (n=5) features of acute
      rejection, and four control renal biopsies with no detectable abnormalities by
      RNA in situ hybridization. The expression of ICAM-1 and VCAM-1 protein was also
      assessed by immunohistochemical staining of frozen sections. RESULTS: In controls
      and nonrejecting graft biopsies, the signals of the ICAM-1 and VCAM-1 transcripts
      in vascular cells were almost negligible. Specific signals of ICAM-1 and VCAM-1
      mRNAs were detected on the endothelial cells of small muscular arteries in most
      cases with acute renal allograft rejection. The messages for ICAM-1 and VCAM-1
      were also detected on arterial smooth muscle cells in all the five cases with
      severe type III rejection. CONCLUSIONS: These results suggest that the induced
      appearance of ICAM-1 and VCAM-1 on the vascular cells of acutely rejecting renal
      transplants was related to actual cellular synthesis and that both adhesion
      molecules could act together in the rejection process. They also suggest that the
      expression of ICAM-1 and VCAM-1 genes by arterial smooth muscle cells may be an
      important cause of transmural arteritis in severe acute renal allograft
      rejection.

PMID- 10910277
TI  - Human herpesvirus-6 antigenemia after liver transplantation.
AB  - BACKGROUND: Human herpesvirus (HHV)-6 has recently been reported in liver
      transplant patients. It infects and causes dysfunction in hepatic transplants,
      which provides serious differential diagnostic problems between allograft
      rejection and viral infection. The diagnosis of posttransplantation HHV-6
      infection is usually based on serology or on polymerase chain reaction detection
      of viral DNA in peripheral blood specimens. However, serology does not tell the
      exact time of the infection, and detection of viral DNA by polymerase chain
      reaction may also indicate a latent infection in seropositive patients. Here we
      report the diagnostic use of frequent monitoring of HHV-6 antigenemia after liver
      transplantation. METHODS: Altogether 622 blood specimens from 51 consecutive
      adult liver transplant patients were analyzed. The diagnosis was based on
      demonstration of HHV-6-specific antigens in peripheral blood mononuclear cells
      using immunoperoxidase staining and monoclonal antibodies and on serology.
      RESULTS: During the first year (7-280 days) after transplantation, HHV-6
      infection was diagnosed in 11 (22%) of 51 patients. HHV-6 early antigens, as well
      as HHV-6 variant B antigens, were detected in all 11 patients. HHV-6 diagnosis
      was confirmed by serology. The episode of HHV-6 antigenemia usually lasted for
      several weeks together with mild, if any, clinical signs of the infection. A
      significant graft dysfunction was associated with HHV-6 antigenemia in 8 of 11
      patients, and viral antigens were also detected in the liver biopsy specimens of
      3 of these patients. CONCLUSIONS: An active HHV-6 infection can be diagnosed from
      peripheral blood by detection of virus-specific antigens in mononuclear cells.
      HHV-6 antigenemia correlated with seroresponse.

PMID- 10910278
TI  - Human herpesvirus-6 in liver transplant recipients: role in pathogenesis of
      fungal infections, neurologic complications, and outcome.
AB  - BACKGROUND: The clinical impact and relevance of human herpesvirus-6 (HHV-6)
      infection in liver transplant recipients, has not been fully discerned. METHODS:
      A prospective study of 80 consecutive liver transplant recipients was performed
      using surveillance cultures for HHV-6 at weeks 2, 3, 4, and 6 after
      transplantation. Viral isolation was used for the detection of HHV-6. RESULTS:
      HHV-6 infection occurred in 39% (31 of 80) of the patients. Patients with HHV-6
      infection were more likely to have hepatocellular carcinoma as underlying liver
      disease (P=.09). Mental status changes of unidentifiable etiology were
      significantly more likely to occur in patients with HHV-6 compared with those
      without (26%, 9 of 31 vs. 6%, 3 of 49, P=.008). HHV-6 infection was an
      independent predictor of invasive fungal infections (odds ratio 8.3, 95%
      confidence interval, 1.2-58.0, P=.03). A significant association between HHV-6
      infection and CMV infection after transplantation, CMV recipient and donor
      serostatus, rejection, or fever of unknown origin, could not be documented.
      Mortality at last follow-up in patients with HHV-6 infection (29%, 9 of 31) was
      significantly greater than those without HHV-6 (6%, 3 of 49, P=.008).
      CONCLUSIONS: Central nervous system complications of unknown etiology after liver
      transplantation may be related to HHV-6 infection. HHV-6 viremia was an
      independently significant predictor of invasive fungal infections and was
      associated with late mortality in liver transplantation recipients.

PMID- 10910279
TI  - Long-term results after conversion from cyclosporine to tacrolimus in pediatric
      liver transplantation for acute and chronic rejection.
AB  - Tacrolimus is beneficial in liver transplantation for reversing steroid-resistant
      acute rejection, and for controlling the process of chronic rejection in
      allograft recipients receiving Cyclosporine- (CyA) based regimens. Very little is
      known about the long-term efficacy of tacrolimus in pediatric transplantation
      after conversion from CyA. Our study examines the long-term outcome after
      conversion to tacrolimus for acute or chronic rejection in pediatric liver
      transplant (LTx) recipients. METHOD: Seventy-three children (age < 18 years)
      receiving their primary LTx under CyA between August 1989 and April 1996 were
      converted to tacrolimus for ongoing acute rejection (n=22, group I) or chronic
      rejection (n=51, group II). Mean age at the time of conversion was 10.2+/-5.5
      years with a mean interval from LTx to conversion of 3.5+/-2.9 (range 0.5-10.1
      years). There were 33 boys and 40 girls. All patients were followed until June
      1999. Mean follow-up was 97.3+/-17.4 months (range 62.4-118.9 months). RESULTS:
      Overall 5-year actual patient survival was 78.1% and 8-year actuarial survival
      was 74.6%. Patients converted to tacrolimus therapy to resolve acute rejection
      (group I) experience significantly better patient and graft survival at 5 and 8
      years than those converted to resolve chronic rejection (group II). Eight-year
      patient survival and graft survival was 95.5 and 90.9% for group I compared to
      74.6 and 53.5% for group II, respectively (long rank P=0.035 and 0.01,
      respectively). Nearly 75% of children were weaned off steroids after conversion.
      There was a marked improvement in hypertension, gum hyperplasia, hirsutism, and
      cushingoid appearance. One child in group I (4.5%) and four children in group II
      (7.8%) developed posttransplant lymphoproliferative disorder after conversion.
      There was an improvement in growth in children who were less than the age of 12
      years at the time of conversion and who were weaned off steroids; more
      significantly girls responded more favorably than boys. CONCLUSION: The benefit
      of transplantation is maintained long-term after conversion to tacrolimus for
      acute or chronic rejection. The response rate was significantly better in group I
      as compared with group 11. Marked improvement in growth, hypertension, and
      reversal of the brutalizing effects of CyA was noted after conversion to
      tacrolimus. The results suggest that early conversion of pediatric liver
      transplant patients is warranted for the treatment of acute and chronic
      rejection, and for improvements in quality of life.

PMID- 10910280
TI  - Minimal blood loss living donor hepatectomy.
AB  - BACKGROUND: Donor hepatectomy with maximal safety while preserving graft
      viability is of principal concern in living donor liver transplantation. There
      are compelling reasons for avoiding blood transfusion, even with autologous
      blood, to avoid the potential risks it imposes on healthy donors. This study aims
      to describe the surgical technique and clinical outcomes of living donor
      hepatectomy with minimal blood loss requiring no blood transfusion. METHODS:
      Donor hepatectomy was performed in 30 living donors according to a detailed
      preoperative imaging study of the vascular and biliary anatomy. Liver parenchymal
      transection was carried out with strict adherence to a meticulous surgical
      technique without vascular inflow occlusion to either side of the liver. Pre-,
      intra-, and postoperative data were gathered, and factors related to blood loss
      were analyzed retrospectively. RESULTS: The intraoperative blood loss ranged from
      20 to 300 ml with a mean of 72.0+/-58.9 ml (median, 55 ml), and neither
      homologous nor autologous blood transfusion was required in any of the donors
      intra- and postoperatively. All 30 donors were discharged with minimal
      complications, and remain well at a mean follow-up of 24 months after donation.
      Excellent graft viability was verified by the fact that all 30 recipients are
      alive and well with a few manageable complications. The actual graft and patient
      survival are both 100% at the time of writing. CONCLUSIONS: Regardless of the
      extent of donor hepatectomy, blood loss can and should be kept to a minimum, and
      living donor hepatectomy without blood transfusion is a realistic objective.

PMID- 10910282
TI  - Anti-Gal antibodies in humans and 1, 3alpha-galactosyltransferase knock-out mice.
AB  - BACKGROUND: Due to the absence of alphaGAL epitopes, humans and
      galactosyltransferase knock-out (GALT/ KO) mice express high levels of anti-Gal
      antibodies. We describe the properties of mouse anti-GAL antibodies. METHODS:
      Anti-GAL IgG antibodies were quantified by affinity purification. Antibody
      affinities and avidities were determined in direct binding and competition
      assays. Antibody-mediated rejection was investigated using hyperimmunized GALT/KO
      mice as recipients of GAL+ heart allografts. RESULTS: In young GALT/KO mice the
      levels of anti-GAL antibodies were low. Immunization of GALT/KO mice resulted in
      increased anti-GAL antibody expression. In mouse serum 0.6% of IgG was specific
      for alphaGAL compared to 0.5% in human serum. The avidity of purified mouse and
      human anti-GAL IgG was 30 and 6 nM, the affinity 15 and 50 microM, respectively.
      The isotype distribution in mouse and human anti-GAL IgG appeared to be similar
      to the isotype distribution in normal sera. The affinity of mouse and human anti
      GAL IgM was 150 and 750 microM, respectively. Immunized GALT/KO recipients of
      GAL+ heart transplants rejected their grafts within 2 hr although nonimmunized
      GALT/KO mice retained their grafts for up to 6 days. Immunohistological
      examination of the rejected GAL+ hearts revealed massive deposition of IgM and
      IgG on endothelial cells of the graft with a concomitant deposition of
      complement. CONCLUSIONS: Our studies demonstrate that anti-GAL antibodies from
      immunized GALT/KO mice bind alphaGAL with an avidity/affinity similar to human
      anti-GAL antibodies and are able to induce hyperacute rejection of GAL+ heart
      allografts.

PMID- 10910281
TI  - Specific suppression of interleukin 2 biosynthesis by synthetic antisense
      oligodeoxynucleotides does not influence allograft rejection.
AB  - BACKGROUND: Interleukin (IL)-2 supplementation can reverse both blood transfusion
      induced tolerance to kidney allografts and spontaneous tolerance to liver
      allografts in rats. Moreover, IL-2 expression is frequently suppressed in models
      of allograft tolerance. The failure of IL-2 biosynthesis might therefore play a
      critical role in tolerance induction. METHODS: Three antisense
      oligodeoxynucleotides (AS-1, AS-2, AS-3) to rat IL-2, and a control oligo (C-1)
      consisting of a scrambled version of AS-1, were evaluated for gene-specific
      suppression of IL-2 biosynthesis in vitro and in vivo, and for their effects on
      kidney allograft survival. Reverse transcriptase-polymerase chain reaction and IL
      2 protein assays were used to assay concanavalin A-driven IL-2 biosynthesis by
      lymph node lymphocytes in vitro. PVG recipients of Dark Agouti kidney allografts
      were treated with the oligos. Graft survival and IL-2 biosynthesis by reverse
      transcriptase-polymerase chain reaction in spleen and graft biopsy specimens were
      assessed. RESULTS: The AS-1 oligo, but not the AS-2, AS-3 or C-1 oligos,
      suppressed concanavalin A-driven IL-2 biosynthesis for the 4 days of culture.
      This effect was dependent on delivery of the AS-1 oligo with lipofectamine.
      Supplementation with exogenous IL-2 reversed the suppression of lymphocyte
      proliferation in AS-1-treated cultures. Administration of AS-1 intravenously at
      10 mg/kg/day to PVG recipients of Dark Agouti kidney allografts suppressed IL-2
      (but not IL-6, interferon-gamma, or tumor necrosis factor-alpha) synthesis in the
      grafts of seven of nine rats, as measured in biopsy specimens taken at days 2-7.
      By contrast, all nine control grafts strongly expressed IL-2. However, neither
      graft histopathology nor graft survival was affected. CONCLUSIONS: Antisense
      oligonucleotides can powerfully suppress IL-2 biosynthesis in vitro and in
      allograft recipients in vivo, but this does not affect kidney allograft
      rejection.

PMID- 10910283
TI  - Involvement of antibody-dependent apoptosis in graft rejection.
AB  - BACKGROUND: Both humoral factors and apoptosis have been recently suggested to
      play a role in chronic allograft rejection. However, a link between
      alloantibodies and grafted cell apoptosis has never been proposed. Using the
      aortic allograft model in the rat, we have previously demonstrated the presence
      of IgG associated with the disappearance of donor endothelial and medial smooth
      muscle cells. In the present study, we tested the interaction between recipient
      allosera, enriched with antibodies by presensitization, and primary culture of
      cardiovascular cells of donor origin. METHODS: For this purpose endothelial
      cells, smooth muscle cells, adventitial fibroblasts, and cardiac myocytes of
      donor origin were cultured. Binding of alloantisera to these cells was analyzed
      by flow cytometry. Apoptosis of donor cells was evaluated by Tdt-mediated d' UTP
      FITC nick end labeling, 4',6-diamidino-2-phenylindole and DNA ladder techniques.
      The alloantisera were compared with anti-MHC class I monoclonal antibodies.
      Finally the colocalization of antibodies and apoptosis was investigated in vivo.
      RESULTS: In vitro, alloantisera bind to cardiovascular cells of donor origin.
      These cells expressed MHC class I but not MHC class II. There was a partial
      competition between anti-MHC I mouse monoclonal antibody and alloantisera mainly
      of the IgG isotype. Alloantisera bound to, but did not induce lysis of, donor
      RBC. Alloantisera induced apoptosis of donor cardiovascular cells as assessed by
      the typical morphological aspect of the donor cells after 24 hr of incubation.
      These data were confirmed by the Tdt-mediated d' UTP-FITC nick end labeling
      positivity of the cells and the fragmentation of the nucleus visualized by 4',6
      diamidino-2-phenylindole and DNA ladder techniques. Similar apoptosis was induced
      by specific monoclonal antibodies directed against the MHC class I of donor
      cells. Primary culture of similar vascular cells of recipient origin was
      insensitive to alloantisera directed against donor alloantigens. Finally, in
      vivo, using allopresentization and aortic allografts, an association of
      alloantibody binding and endothelial cell apoptosis was observed at day 5, and a
      similar association with smooth muscle cell apoptosis on day 12 after grafting.
      CONCLUSION: These data demonstrate the role of humoral injury in chronic
      allograft rejection and suggest new therapeutical approaches focused on the
      induction of resistance to antibody-dependent apoptosis.

PMID- 10910285
TI  - Synergistic effect of anti-T cell receptor monoclonal antibody and 15
      deoxyspergualin on cardiac xenograft survival in a mouse-to-rat model.
AB  - BACKGROUND: Successful xenograft transplantation faces several obstacles
      including the presence of xenoantibodies, natural killer cell- and macrophage
      mediated rejection, and T lymphocyte activation. METHODS: A mouse-to-rat cardiac
      xenograft model was used to examine the synergistic effect of anti-T cell
      receptor (TCR) monoclonal antibodies (mAb) and 15-deoxyspergualin (DSG) on graft
      survival. RESULTS: Pretransplantation injections (days -5, -3, and -1) of anti
      TCR mAb (500 microg/kg/day) combined with continuous i.p. infusion of DSG (5
      mg/kg/day) from day -7 to 28 significantly prolonged graft survival compared to
      untreated controls (3.3+/-0.5 vs. 44.2+/-5.6 days, P<0.001). Postoperative
      splenectomy combined with discontinuation of all other treatment on day 28
      enhanced graft survival in rats treated with anti-TCR mAb and DSG to 71.0+/-2.5
      days. Histological examination of grafts showed characteristic signs of vascular
      rejection: interstitial edema and hemorrhage, and polymorphonuclear cell
      infiltration. Antimouse antibody titers in recipients were increased upon
      rejection in each group that received a xenograft. Flow cytometry analysis showed
      a markedly decreased T cell population and a relatively increased mature B cell
      population (IgM(bright)/IgD(dull)) in spleens of rats treated with anti-TCR mAb
      and DSG on day 28. CONCLUSIONS: The mechanism of prolonged xenograft survival in
      this model may include inhibition of antibody production by arrest of B-cell
      maturation during development from IgM(dull)/IgD(bright) mature B cells to
      antibody producing cells, and inhibition of T cell activation. The rejection seen
      in our model may be caused by xenoreactive antibodies and may be associated with
      T cells, natural killer cells, and macrophages.

PMID- 10910284
TI  - CD8+ T cells contribute to the development of transplant arteriosclerosis despite
      CD154 blockade.
AB  - BACKGROUND: The CD40-CD154 receptor-ligand pair plays a critical role in
      allograft rejection by mediating the activation of endothelial cells, antigen
      presenting cells, and T cells. Blockade of this interaction prevents acute
      allograft rejection and leads to prolonged allograft survival in numerous
      experimental models, but in most cases indefinite graft survival is not achieved
      due to evolving transplant arteriosclerosis. In this study, we have used a model
      of transplant arteriosclerosis to investigate whether CD4+ and CD8+ T cells are
      differentially affected by CD154 blockade. METHODS: BALB/c (H2d) aortic grafts
      were transplanted into C57BL/6 (H2b) recipients treated with anti-CD154
      monoclonal antibody in the presence or absence of CD8+ T-cell depletion.
      Histology and morphometric measurements were performed on day 30 after
      transplantation. RESULTS: Only combined treatment with anti-CD154 and anti-CD8
      monoclonal antibodies resulted in a significant reduction of intimal
      proliferation (33 +/-10% vs. 67+/-14%; untreated control). Administration of
      either antibody alone did not produce this effect. Thymectomy did not alter the
      degree of intimal proliferation observed in any of the treatment groups.
      CONCLUSIONS: Our data provide direct evidence that CD8+ T cells are not targeted
      effectively by CD154 blockade and that the transplant arteriosclerosis seen after
      CD154 blockade is not due to recent thymic emigrant T cells.

PMID- 10910286
TI  - Effects on human and nonhuman primate immune response of a new rat anti-CD2
      monoclonal antibody.
AB  - BACKGROUND: Nonhuman primate models are highly clinically relevant in
      transplantation. The development of immunosuppressive tools or a tolerogenic
      regimen for primate models therefore represents an important goal of
      transplantation immunological research. Hence, we have developed a rat monoclonal
      antibody (mAb) that recognizes the CD2 molecule (LO-CD2b) on both human and
      nonhuman primate cells. METHODS: The LO-CD2b mAb has been characterized by flow
      cytometry, E-rosetting inhibition, and Western blotting. In vitro inhibition of
      immune responses by LO-CD2b was assessed after both mitogenic and allogeneic
      stimulation in mixed lymphocyte reactions (MLR). Several LO-CD2b dose and time
      responses were tested. In vivo, peripheral and lymph node T-cell depletion was
      examined both by flow cytometry and immunohistology in 10 baboons that received
      intravenous injection of LO-CD2b at different doses and time courses.
      Xenosensitization (anti-rat) was assessed by ELISA. Renal allograft survival was
      followed in two baboons treated with iterative LO-CD2b injections. RESULTS: In
      vitro, LO-CD2b binds a lymphocyte antigenic determinant of 52 kDa that is
      recognized by other well-characterized anti-CD2 mAbs (T11, Leu5b). LO-CD2b
      recognized natural killer CD2+ cells. Administration of 200 ng/ml LO-CD2b almost
      completely inhibited human and baboon mitogenic stimulation. Allogeneic baboon
      and human MLR were completely inhibited by the addition of LO-CD2b (at 312 ng/ml)
      on the day of the initiation of culture; when added after 1 or 2 days, LO-CD2b
      still provided a significant MLR inhibition (>50%). Incubation of LO-CD2b with
      baboon peripheral blood mononuclear cells produced very low cytokine levels
      (interferon-y, tumor necrosis factor-alpha, interleukin 2). In secondary MLR,
      baboon peripheral blood mononuclear cells previously incubated with LO-CD2b were
      unable to respond to a second allogeneic stimulation but were able to react to
      mitogens. In vivo, within the first hour after LO-CD2b injection (at 0.15, 0.5,
      and 2 mg/kg), an 85-90% peripheral depletion of CD2+ cells was observed. A
      partial T-cell depletion in inguinal lymph nodes was seen after 1 week. The
      mechanism of peripheral T-cell depletion could have been antibody-dependent cell
      cytotoxicity or opsonization but was complement independent. Iterative LO-CD2b
      injections (12 days at 0.35 mg/kg) slightly prolonged the renal allograft
      survival in two baboons. CONCLUSION: LO-CD2b is a nonactivating rat anti-CD2 mAb
      able to strongly inhibit both mitogenic and allogeneic responses in human and
      nonhuman primates. In vivo, LO-CD2b provides a rapid peripheral T-cell depletion,
      which is reversible within days after the cessation of injections. This rat mAb
      represents a very important tool for in vivo experimental investigation in
      nonhuman primates because it similarly reacts against human T cells in vitro.

PMID- 10910287
TI  - Prolonged survival of heart allografts from p53-deficient mice.
AB  - BACKGROUND: Acute rejection of the heart allograft is the major cause of heart
      failure in the first month after transplantation. Most studies on the prevention
      of acute rejection have concentrated on immune suppression of the recipients,
      whereas little is known about the effects of genetically manipulated donor organs
      on heart allograft survival. Herein, we describe a mouse model of heart
      allografts donated by p53-/- mice that can prolong the survival time of the
      grafts. METHODS: Hearts of p53-/- or p53+/+ C57BL/6J mice were grafted to the
      neck carotid artery and jugular vein of BALB/c mice using a cuff technique. The
      graft survival was observed daily. The hearts were analyzed using several
      techniques, including histology, immunofluorescence, terminal deoxynucleotidyl
      transferase-mediated dUTP-biotin nick end labeling (TUNEL), and Western blot
      analysis. RESULTS: p53+/+ allografts ceased beating at 7.6+/-0.5 days, whereas
      p53-/- hearts were beating at 10.5+/-1.1 days after transplantation (P<0.01).
      Mean histological rejection scores were significantly lower in allografts donated
      by p53-deficient mice. Furthermore, apoptotic cells, determined by TUNEL and a
      reagent kit for detection of cardiac apoptosis, were of high numbers in the
      allograft sections from wild-type hearts but rare in p53-/- allografts (4.2+/-1.3
      vs. 0.7+/-0.5/250x field). Immunofluorescence staining and Western blot analysis
      revealed that high levels of p53 and proapoptotic protein Bax were expressed in
      wild-type grafts but not p53-/- allografts. Interestingly, Bcl-2, an
      antiapoptotic protein, was abundant in cardiac allografts from p53-/- mice and
      almost undetectable in grafts from wild-type mice. CONCLUSIONS: Thus, p53 is
      involved in cardiac apoptosis induced by alloimmune reaction, and prolonged
      survival of heart allografts can be achieved when p53 is lacking.

PMID- 10910288
TI  - Rat cytomegalovirus infection in kidney allograft recipients is associated with
      increased expression of intracellular adhesion molecule-1 vascular adhesion
      molecule-1, and their ligands leukocyte function antigen-1 and very late antigen
      4 in the graft.
AB  - BACKGROUND: Cytomegalovirus (CMV) infection is suggested to be a risk factor for
      chronic rejection. We have recently shown that rat CMV (RCMV) increases the
      inflammatory response and accelerates chronic rejection in a model of rat kidney
      allograft. In this study, the early inflammatory response and time-related
      expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) and their ligands, leukocyte function antigen-1 (LFA
      1) and very late antigen-4 (VLA-4), in the grafts were investigated in RCMV
      infected rats and compared to noninfected rats developing chronic rejection.
      METHODS: Transplantations were performed in a rat strain combination of DA (RT1a)
      >BN (RT1n) receiving triple drug immunosuppression. One group of rats was
      infected with RCMV, and the other was left uninfected. The grafts were harvested
      at different time points after transplantation. The adhesion molecules, their
      ligands and activation markers, MHC class II antigens and interleukin-2-receptors
      (IL-2-R), were demonstrated by monoclonal antibodies and immunoperoxidase
      staining from frozen sections of the grafts. Graft histology was evaluated
      according to the Banff criteria. RESULTS: RCMV caused a significant, prolonged
      increase of VCAM-1 and ICAM-1 expression in the vascular endothelium compared to
      the noninfected grafts. Also, the number of cells expressing activation markers,
      LFA-1 and VLA-4 was significantly enhanced in these animals. Significantly
      enhanced histological changes of chronic rejection were seen in the RCMV-infected
      group. CONCLUSIONS: Prolonged, increased expression of ICAM-1 and VCAM-1, and
      increased numbers of inflammatory cells expressing their ligands in the CMV
      infected grafts, were associated with accelerated chronic allograft nephropathy.

PMID- 10910289
TI  - Preferential induction of Th1 responses by functionally mature hepatic (CD8alpha-
      and CD8alpha+) dendritic cells: association with conversion from liver transplant
      tolerance to acute rejection.
AB  - BACKGROUND: Liver grafts are accepted across major histocompatibility barriers in
      mice without immunosuppressive therapy. Potentially tolerogenic immature donor
      dendritic cells (DC) may play a key role in this phenomenon, but recovery of
      purified DC from normal livers for functional analysis is inherently difficult.
      Administration of in vitro propagated immature donor DC to recipients of
      different types of allograft can prolong transplant survival. By contrast, marked
      increases in donor liver DC as the result of Flt3 ligand (FL) administration and
      the resulting augmentation of allostimulatory activity within host lymphoid
      tissue, is associated with acute graft rejection. Here, we compared the capacity
      of in vitro generated normal liver immature DC and FL-treated donor liver DC to
      induce alloimmune CD4+ T helper (Th) 1/Th2 and CD8+ T cytotoxic (Tc) 1/Tc2
      responses, in vitro and in vivo. METHODS: B10 (H2b, IAb) immature liver DC were
      propagated from normal hepatic nonparenchymal cells in granulocyte macrophage
      colony stimulating factor (GM-CSF) for 6-8 days. Freshly isolated DC from livers
      of FL-treated mice (FL-liver DC) were cultured overnight (o/n) in GM-CSF, and
      both myeloid (CD11c+ CD8alpha-) and lymphoid DC (CD11c+ CD8alpha+) flow-sorted
      for functional analysis. Proliferative activity and production of interferon
      (IFN)-gamma, interleukin (IL)-4, and IL-10 by naive C3H (H2k, IEk) T cells in
      response to DC stimulation was assessed by [3H]thymidine incorporation, and by
      multicolor flow cytometric analysis, respectively, after 3-day mixed leukocyte
      reactions. To investigate their in vivo trafficking, B10 DC were injected
      subcutaneously into normal C3H mice. Sections of lymphoid tissue were
      immunostained for donor MHC class II+ (IAb+) cells, and for IFN-gamma, IL-4, and
      IL-10 production. Donor cells and clusters of specific cytokine-secreting cells
      were enumerated. RESULTS: Both in vitro propagated normal liver-derived DC, and
      freshly isolated bulk FL-liver DC showed an immature phenotype (MHC class II(lo),
      CD40-, CD80-, and CD86-) and were weak stimulators of naive allogeneic T cells.
      After o/n incubation in GM-CSF, both CD8alpha- and CD8alpha+ FL-liver DC
      exhibited marked up-regulation of surface MHC class II and costimulatory
      molecules, and acquired potent stimulatory activity for Th1 (mainly) and Th2
      cells. Both in vitro propagated immature DC and o/n-cultured mature FL-liver DC
      homed in vivo to host lymphoid tissues, but with different kinetics. Whereas the
      mature allogeneic FL-liver DC induced IFN-gamma+ clusters in splenic T-cell areas
      within 2 days, the IFN-gamma response to immature DC was much slower and weaker.
      CONCLUSIONS: FL-treated donor livers that are rejected acutely contain markedly
      enhanced numbers of myeloid (CD8alpha-) and lymphoid (CD8alpha+) DC, many of
      which are capable of maturing rapidly into strong inducers of Th1 and Tcl
      responses. Substantial differences in quantity, and both the phenotypic and
      functional characteristics of the DC constituency of donor livers, may contribute
      significantly toward the distinct outcomes of liver transplant tolerance and
      rejection.

PMID- 10910290
TI  - Early up-regulation of macrophages and myofibroblasts: a new marker for
      development of chronic renal allograft rejection.
AB  - BACKGROUND: Increased numbers of macrophages and myofibroblasts are observed to
      occur in chronic renal allograft rejection (CR). The aim of this study was to
      examine the expression of cellular markers for the macrophage and myofibroblast
      in early renal transplant biopsy specimens and correlate these findings with
      allograft outcome. METHODS: The first postengraftment biopsy specimens from 53
      patients who underwent renal transplantation between January 1993 and December
      1995 were studied using immunohistochemistry with antibodies to alpha-smooth
      muscle actin, which identifies myofibroblasts and CD68, a marker for monocytes
      and macrophages. Patients were followed until December 1998 (mean follow-up 4.7+/
      1.2 years). RESULTS: Nine patients had progressed to CR by the time of the study,
      whereas 44 patients continued to have stable renal function. A marked increase in
      both macrophages (P=0.02) and myofibroblasts (P=0.04) was noted in the first
      biopsy specimen obtained after engraftment in the patients who developed CR
      compared with those with stable allograft function. There was a positive
      correlation between alpha-smooth muscle actin and collagen expression (P=0.0001).
      CONCLUSION: Significant increases in macrophages and myofibroblasts occur in the
      first renal biopsy specimen in those patients who later develop CR.

PMID- 10910291
TI  - Acute rejection presenting as nephrotic syndrome.
AB  - BACKGROUND: Early diagnosis and treatment of acute rejection is important to
      prevent continued renal injury. Acute rejection most commonly presents with
      asymptomatic rise in serum creatinine. Proteinuria associated with acute
      rejection is well established; however, there is limited documentation of the
      presentation of acute rejection as nephrotic syndrome in the literature. METHODS
      AND RESULTS: We report a renal transplant patient who presented with early onset
      nephrotic syndrome without change in serum creatinine, whose allograft biopsy
      confirmed acute glomerulitis and vascular rejection. Treatment of the acute
      rejection was accompanied by resolution of the nephrotic syndrome. A second
      episode of acute rejection was also manifested as nephrotic range proteinuria.
      CONCLUSION: The nephrotic syndrome in early post-transplantation period should
      prompt a work-up for acute rejection even in the absence of the common findings
      of this complication.

PMID- 10910292
TI  - Human parvovirus B19 infection presenting as persistent anemia in renal
      transplant recipients.
AB  - BACKGROUND: Immunosuppression cannot be achieved without immunosuppressive
      effects. Human Parvovirus infection is known to occur after organ
      transplantation. We present our experience with Parvovirus infection in two
      cases. METHODS AND RESULTS: Two kidney transplant recipients developed
      symptomatic anemia requiring blood transfusions. Common causes of anemia, such as
      gastrointestinal bleeding, iron/vitamin deficiencies, hemolysis, and drug
      toxicities, were ruled out. A peripheral smear revealed low reticulocyte count.
      Bone marrow examination showed hypoplastic bone marrow with intranuclear
      inclusions suggestive of human Parvovirus. This was confirmed by
      immunohistochemical analysis. Treatment with i.v. immunoglobulin G resulted in a
      dramatic sustained response. Transplant kidney function remained stable.
      CONCLUSION: Human Parvovirus infections should be considered in immunosuppressed
      individuals with anemia with poor bone marrow response. Bone marrow examination
      can reveal viral inclusions and can be confirmed by immunohistochemical analysis.
      Intravenous immunoglobulin G results in resolution of anemia.

PMID- 10910293
TI  - Chronic exercise training effects on immune function.
AB  - PURPOSE: This paper reviews the recent literature on the chronic effects of
      exercise training on immune function in humans. There is a general perception by
      athletes and other physically active individuals that regular moderate activity
      enhances, whereas intense exercise suppresses, resistance to minor illnesses such
      as upper respiratory tract infection (URTI). This perception is supported by
      epidemiological data in endurance athletes and limited data from intervention
      studies using moderate exercise in previously untrained individuals. The
      apparently high incidence of URTI among endurance athletes has prompted interest
      the relationship between chronic exercise training and immune function. Whereas
      immune cell number is generally normal during intense exercise training, recent
      evidence suggests that prolonged periods of intense training may lead to slight
      impairment in immune parameters such as neutrophil function, serum and mucosal
      immunoglobulin levels, plasma glutamine concentration, and possibly natural
      killer cell cytotoxic activity. In contrast. moderate exercise training has
      either no effect on, or may stimulate, these immune parameters. CONCLUSION:
      Whereas athletes are not clinically immune deficient, it is possible that the
      combined effects of small changes in several immune parameters may compromise
      resistance to minor illnesses such as URTI. Strategies to prevent URTI in
      athletes include avoiding overtraining, providing adequate rest and recovery
      during the training cycle and after competition, limiting exposure to sources of
      infection, ensuring adequate nutrition, and possibly vitamin C supplementation.
      It is uncertain at present whether moderate exercise training is helpful in
      preventing infectious illness among the wider population.

PMID- 10910294
TI  - Glutamine and arginine: immunonutrients for improved health.
AB  - There is considerable literature demonstrating that specific nutrients can
      influence immune function in health and disease. This review will examine the
      literature and the rational for classifying two amino acids, glutamine (gln) and
      arginine (arg), as "immunonutrients" during infections. An understanding of
      immune defenses during infections (virus, parasite, bacteria, protozoa) and
      metabolism of gln and arg by immune cells is necessary to understand how these
      nutrients can influence specific functions of the immune system. This review
      focuses on several key clinical studies in immunosuppressed individuals (burn
      patients, individuals with cancer and HIV infection, and those undergoing surgery
      or who have experienced major traumas) that have tested the hypothesis that the
      provision of gln and/or arg is beneficial to immune function and clinical
      outcome. These clinical studies support the dietary "essentiality" of these two
      nutrients for improving immune responses in most immunosuppressive states
      associated with high rates of infection. However, the role of these nutrients in
      modulating the immune changes that occur with exercise in healthy athletes
      demands additional experiments.

PMID- 10910295
TI  - Dietary fats and immune status in athletes: clinical implications.
AB  - Athletes are competitive, train at very high levels with inadequate rest, consume
      too few calories, avoid fats, and may be at increased risk of infections. The
      immune system is sensitive to both fat intake and intense exercise, suggesting
      that athletes may have suppressed immune function. It has been reported that many
      athletes consume about 25% fewer calories than the estimated expenditure, leading
      to low intakes of some essential micronutrients and fats. Acute exercise has been
      shown to increase inflammatory and decrease antiinflammatory immune factors and
      may increase oxidant stress. Chronic exercise appears to improve immune
      competence. Lipids are powerful mediators of the immune system, and they may
      modulate the immunosuppressive effects of strenuous exercise. Studies have shown
      that a low-fat high-carbohydrate diet (15% fat, 65% CHO, 20% protein of total
      calories), typically eaten by athletes, increases inflammatory and decreases
      antiinflammatory immune factors, depresses antioxidants, and negatively affects
      blood lipoprotein ratios. Increasing total caloric intake by 25% to match energy
      expenditure and the dietary fat intake to 32% in athletes appears to reverse the
      negative effects on immune function and lipoprotein levels reported on a low-fat
      diet. Increasing the dietary fat intake of athletes to 42%, while maintaining
      caloric intake equal to expenditure, does not negatively affect immune competency
      or blood lipoproteins, whereas it improves endurance exercise performance at 60
      80% of VO2max in cyclists, soldiers, and runners. There is no evidence that
      higher fat intakes (up to 42% of total calories), in calorically balanced diets,
      increase the risk of cancer, but studies are needed to determine whether the
      beneficial effects of higher fat diets in athletes reduce their rate of
      infections.

PMID- 10910296
TI  - Acute exercise effects on the immune system.
AB  - PURPOSE: In recent years, health professionals have placed increased attention on
      the benefits of physical activity for maintaining health in the general
      population as well as regaining health in many disease states. Conversely,
      reports of apparent decreases in immune cell function after acute exercise are
      widespread in the literature. The purpose of this article is to evaluate
      critically the available data and currently employed methods, with the aim of
      establishing whether genuine or artefactual alterations of immune function are
      being reported. During and immediately after exercise, the total number of white
      blood cells in peripheral blood samples increases, such that the relative
      proportions of cell types within the leukocyte pool are altered. A number of
      important areas of discussion arise from these shifts in the number of
      circulating cells after exercise, not least of which is the artefactual effects
      they may have on currently employed assays of immune cell function. Recent
      advances in methodology are beginning to call into question the assumption that
      acute exercise has any genuine immunosuppressive effect. CONCLUSION: At present,
      there is little evidence to suggest that the range of acute exercise intensities
      and durations recommended by ACSM has a major detrimental effect on the function
      of individual T- and B-lymphocytes, natural killer cells and neutrophils.
      Although individual cells may not be as adversely affected as previously
      supposed, it is unclear whether the numerical content of the circulating
      population is an important clinical consideration.

PMID- 10910297
TI  - Is infection risk linked to exercise workload?
AB  - Anecdotal, survey, and epidemiological data suggest that endurance athletes are
      at an increased risk for upper respiratory tract infection (URTI) during periods
      of heavy training and the 1 - to 2-wk period after race events. The majority of
      athletes, however, who participate in endurance race events do not experience
      illness. Of greater public health importance is the consistent finding of a
      reduction in URTI risk reported by fitness enthusiasts and athletes who engage in
      regular exercise training while avoiding overreaching/overtraining. Although it
      naturally follows that infection risk should in some way be linked to acute and
      chronic exercise-induced alterations in immunity, attempts thus far to measure
      this association have been unsuccessful. There is growing evidence that for
      several hours subsequent to heavy exertion, several components of both the innate
      and adaptive immune system exhibit suppressed function. The immune response to
      heavy exertion is transient, however, and further research on the mechanisms
      underlying the immune response to prolonged and intensive endurance exercise is
      necessary before meaningful clinical applications can be drawn. Some attempts
      have been made through chemical or nutritional means (e.g., indomethacin,
      glutamine, vitamin C, and carbohydrate supplementation) to attenuate immune
      changes after intensive exercise to lower the risk of infection. No consistent
      relationship between nutritional interventions, exercise immunology, and
      alteration in URTI risk has yet been established.

PMID- 10910299
TI  - Viral hepatitis and exercise.
AB  - Increase awareness and publicity of human immunodeficiency virus (HIV) has
      fostered a heightened sense of concern regarding the transmission of infectious
      agents during sports and athletic competition. Although the potential risk is
      low, there are other unanswered questions and issues regarding infectious disease
      and sports. Viral hepatitis is a common infection and predominantly affects the
      young who are most likely to lead active lives and engage in both amateur and
      competitive sport-related activity. This article summarizes the common forms of
      viral hepatitis and the associated clinical syndromes. In addition, a review of
      the literature addressing the effect of exercise and the various states of liver
      disease is presented. Finally, I will address the question regarding
      participation and return to physical activity following acute viral hepatitis, as
      well as chronic hepatitis.

PMID- 10910300
TI  - Infectious diseases in sports.
AB  - Participation in sports in on the increase; this article addresses the
      intersection of sports and infectious diseases. Some infections occur with
      increased incidence in sports; others have an increased impact in that setting.
      Addressed in this article are issues of diagnosis, prevention, and management of
      many of these infections. Included are skin/soft tissue infections, infections
      related to water exposure, viral infections, infections related to blood
      exposure, and vaccinations.

PMID- 10910298
TI  - Mechanisms of exercise limitation in HIV+ individuals.
AB  - Cardiopulmonary exercise testing (CPX) is an important diagnostic tool for both
      clinical and research purposes in HIV positive (HIV+) individuals. Important
      information can be obtained from the gas exchange responses that can elucidate
      heart, lung, peripheral vascular, pulmonary vascular, and muscle abnormalities in
      this population. A large percentage of these patients are deconditioned, respond
      well to exercise training, and have no intrinsic limitation to exercise. Results
      of a progressively increasing CPX can be used to: 1) design an exercise
      prescription for aerobic training in HIV+ individuals; 2) identify and refer
      patients with subtle abnormalities of gas exchange for further diagnostic studies
      to exclude early infectious complications: and 3) evaluate the improvements in
      maximal oxygen uptake, lactic acidosis threshold, and gas exchange kinetics as
      result from an aerobic exercise training program. Gas exchange kinetic analysis
      of constant work rate tests can provide similar information in a nonmaximal,
      reproducible, readily obtainable format. Both progressively increasing and
      constant work rate CPX tests provide important information on the changes in
      oxygen flow from the environment to the exercising muscle that occur with aerobic
      exercise training. Finally, a case study involving the exercise prescription for
      HIV+ individuals is reviewed as well as the risk of transmission of HIV during
      competitive sports competition events.

PMID- 10910301
TI  - Picture of the month. Phytophotodermatitis.

PMID- 10910302
TI  - Prescription diversion among patients in a family practice clinic.

PMID- 10910303
TI  - More points on vagally mediated atrial fibrillation.

PMID- 10910304
TI  - Characteristics and experiences of parents and adults who want antibiotics for
      cold symptoms.
AB  - OBJECTIVE: To characterize people who want antibiotics for cold symptoms and to
      suggest reasons for antibiotic expectations. DESIGN: Cross-sectional telephone
      survey in the spring of 1997 (March 10 to May 16). SETTING: Three primary care
      clinics in metropolitan Minneapolis, Minn. PARTICIPANTS: Two hundred forty-nine
      parents of symptomatic children and 256 symptomatic adults contacting their
      medical provider (primary care physician, nurse practitioner, or physician
      assistant) for care of cold symptoms. MAIN DEPENDENT MEASURE: Wanting an
      antibiotic prescription for cold symptoms. RESULTS: Thirty percent of parents and
      50% of symptomatic adults wanted an antibiotic prescription. Factors associated
      with desire for antibiotics differed between groups. Parents who wanted
      antibiotics for their children were more likely than other parents to report
      severe symptoms (odds ratio [OR], 2.11; 95% confidence interval [CI], 1.16-3.85),
      to want relief for their child (OR, 2.63; 95% CI, 1.34-5.46), and to believe that
      antibiotic therapy helps cold symptoms (OR, 1.95; 95% CI, 1.08-3.55). Symptomatic
      adults who wanted antibiotics were more likely than other symptomatic adults to
      report severe cold symptoms (OR, 2.10; 95% CI, 1.22-3.67) that have lasted too
      long (OR, 2.40; 95% CI, 1.31-4.49), to previously have recovered faster with
      antibiotic therapy (OR, 2.82; 95% CI, 1.65-4.89), and to be confident that they
      know how to treat the cold (OR, 1.79; 95% CI, 1.03-3.16). They were less likely
      to believe that too many people take antibiotics for a cold (OR, 0.57; 95% CI,
      0.33-0.98). CONCLUSIONS: Parents may be amenable to clinical messages that other
      treatments may be more effective than antibiotics in managing cold symptoms.
      Experiences of symptomatic adults may conflict with this message. Previous cold
      related medical management and drug resistance might need to be discussed with
      adult patients.

PMID- 10910305
TI  - The family physician's reasonable approach to upper respiratory tract infection
      care for this century.

PMID- 10910306
TI  - Family physicians' role in recruitment of organ donors.
AB  - OBJECTIVE: To determine if family physicians can increase the commitment of
      patients to organ donation. DESIGN: Prospective, systematically randomized, cross
      sectional study. SETTING: Family practice residency medical center associated
      with an urban, community-based teaching institution. PATIENTS: A total of 300
      patients aged 18 years or older, able to give consent, and being seen for non
      life-threatening visits; 247 patients returned valid second questionnaires.
      INTERVENTIONS: Instruments included 2 self-administered questionnaires. All
      patients received questionnaire 1 to be completed in the examination room. They
      also received an informational brochure, a Michigan Secretary of State driver's
      license sticker (donor sticker) and questionnaire 2. Group 1 received the written
      materials only. Group 2 received written materials plus a brief verbal discussion
      by the investigators following a standard protocol. Questionnaire 2 was to be
      completed and returned after the interventions. MAIN OUTCOME MEASURES: Self
      reported completion of donor sticker was used to evaluate commitment to organ
      donation. Knowledge scores were summed for preintervention and postintervention
      means. RESULT: Thirty-three percent of patients had already committed to organ
      donation prior to the study. Of those not previously committed, 40% decided to do
      so after the interventions. There was no statistical difference in the
      recruitment of donors between the 2 intervention groups. Of new donors
      identified, 65% stated their decision was due to written materials provided,
      while 34% attributed this to discussion with a physician. Thirty-five percent of
      the family members made arrangements to donate their own organs after the
      discussion with the patient. There was a significant difference between mean
      pretest and posttest knowledge scores (10 questions; 7.9 vs 9.2; P<.01).
      CONCLUSION: Family physicians can increase the commitment to organ donation
      through a relatively simple intervention.

PMID- 10910307
TI  - Demographic predictors of melanoma stage at diagnosis.
AB  - OBJECTIVE: To examine sociodemographic characteristics as possible predictors of
      late-stage melanoma diagnosis. We hypothesized that late-stage diagnosis would be
      associated with the following: older age, male sex, unmarried status, lower
      educational attainment and income level, rural residence, and cigarette smoking.
      METHODS: We used data from the state tumor registry to study all incident cases
      of melanoma occurring in Florida during 1994 whose stage at diagnosis was
      available (N = 1884). We used multiple logistic regression to determine the
      effects of sociodemographic characteristics on the odds of late-stage (regional
      or distant metastases) diagnosis. RESULTS: There were 243 patients (12.9%)
      diagnosed as having melanoma that had metastasized to either regional lymph nodes
      or distant sites. Patients who were unmarried (odds ratio, 1.5; P= .01), male
      (odds ratio, 2.2; P<.001), or smokers (odds ratio, 2.2; P<.001) or who resided in
      communities with lower median educational attainment (odds ratio, 1.5; P= .048)
      had greater odds of having a late-stage diagnosis. CONCLUSIONS: To detect these
      cancers at an earlier stage and improve outcomes, there should be increased
      educational efforts directed toward physicians who treat these patients. A
      recognition that there may be additional risk factors for late-stage diagnosis,
      beyond the established risk factors, such as family history and excess sun
      exposure, should be included in the initial assessment. Specific public education
      efforts should also be targeted to these patients to increase their self
      surveillance and surveillance of their partners.

PMID- 10910308
TI  - Use of child reports of daily functioning to facilitate identification of
      psychosocial problems in children.
AB  - BACKGROUND: Despite the availability of effective screening measures, physicians
      fail to identify and manage many children with psychosocial problems. Physicians
      are most likely to identify children with psychosocial problems when parents
      voice concerns about their child's functioning. However, few parents express
      concerns to their child's physician, and children's perspectives of their own
      functioning are rarely considered. This study evaluated the potential utility of
      children's reports of their own functioning. METHODS: The Child Functioning Scale
      (CFS) was completed by 107 parents and children and compared with the Pediatric
      Symptom Checklist (PSC) and physician reports on the psychosocial status of each
      child. RESULTS: Physicians identified 20% of the children identified by the PSC.
      Children's self-reported problems on the CFS would have identified 53.3% of these
      children. Additionally, 11.2% of children who did not meet criteria on the PSC
      self-reported problems in daily functioning. CONCLUSION: Collecting information
      about children's perceptions of their own daily functioning could provide
      physicians with an additional tool for the assessment of psychosocial problems.

PMID- 10910309
TI  - Does influenza vaccination exacerbate asthma? Analysis of a large cohort of
      children with asthma. Vaccine Safety Datalink Team.
AB  - CONTEXT: Although influenza vaccination is recommended for children with asthma,
      only a minority are vaccinated. One reason for low influenza vaccine coverage
      among children with asthma may be concern that influenza vaccination may induce
      an exacerbation of asthma. OBJECTIVE: To evaluate the safety of influenza
      vaccination in children with asthma, we studied the incidence of hospitalizations
      and emergency department visits for asthma following influenza vaccination.
      DESIGN: Retrospective cohort study-analysis of population-based computerized
      medical and vaccination records. SETTING: : Four large health maintenance
      organizations on the West Coast of the United States. SUBJECTS: Children with
      asthma 1 through 6 years of age, identified by search of computerized databases
      of medical encounters and pharmacy prescriptions. MAIN OUTCOME MEASURES:
      Exacerbations of asthma. RESULTS: In unadjusted analyses vaccination was
      associated with high rates of asthma exacerbations. However, after adjusting for
      asthma severity using a self-control method, the incidence rate ratios of asthma
      exacerbations after vaccination were 0.58 (95% confidence interval, 0.36-0.95),
      0.74 (95% confidence interval, 0.47-1.17), and 0.98 (95% confidence interval,
      0.76-1.27) during the 3 influenza seasons. CONCLUSIONS: After controlling for
      asthma severity, we found that influenza vaccination does not result in acute
      asthma exacerbations in children. Concern about possible exacerbation of asthma
      is not a valid reason to not vaccinate children with asthma against influenza.

PMID- 10910311
TI  - National patterns of physician activities related to obesity management.
AB  - CONTEXT: National physician practices related to the clinical recognition and
      management of obesity are unknown. OBJECTIVES: To estimate national patterns of
      office-based, obesity-related practices and to determine the independent
      predictors of these practices. DESIGN: Serial cross-sectional surveys of
      physician office visits. SETTING: Ambulatory medical care in the United States.
      PATIENTS: We analyzed 55,858 adult physician office visits sampled in the 1995
      1996 National Ambulatory Medical Care Surveys. Data from the Third National
      Health and Nutrition Examination Surveys, 1988-1994 were used to assess and,
      then, adjust for the underreporting of obesity. MAIN OUTCOME MEASURES: Reporting
      of obesity at office visits and physician counseling for weight loss, exercise,
      and diet among patients identified as obese. RESULTS: Physicians reported obesity
      in only 8.6% of 1995-1996 National Ambulatory Medical Care Surveys visits. The
      22.7% prevalence rate of the Third National Health and Nutrition Examination
      Surveys, 1988-1994 suggests that physicians reported obesity in only 38% of their
      obese patients. Among visits by patients identified as obese, physicians
      frequently provided counseling for weight loss (35.5%), exercise (32.8%), and
      diet (41.5%). Adjusted for population prevalence; however, each service was
      provided to no more than one quarter of all obese patients. While patients with
      obesity-related comorbidities were treated more aggressively, in these patients,
      weight loss counseling occurred at only 52% of the visits. CONCLUSIONS: Specific
      interventions to address obesity are infrequent in visits to US physicians.
      Obesity is underreported and interventions are only moderately likely among
      patients identified as obese, even for those with serious obesity-related
      comorbidities.

PMID- 10910310
TI  - Effectiveness and costs of omeprazole vs ranitidine for treatment of symptomatic
      gastroesophageal reflux disease in primary care clinics in West Virginia.
AB  - OBJECTIVE: To compare clinical, health-related quality of life (HRQL), and
      medical cost outcomes in patients with symptomatic gastroesophageal reflux
      disease (GERD) receiving omeprazole sodium or ranitidine hydrochloride treatment.
      METHODS: A multicenter, randomized, open-label, medical effectiveness trial
      conducted in 5 university-based family medicine clinics. Two hundred sixty-eight
      patients with GERD were recruited and randomly assigned to omeprazole sodium, 20
      mg once daily, or ranitidine hydrochloride, 150 mg twice daily, for up to 6
      months. Main outcome assessments included the Gastrointestinal Symptom Rating
      Scale (GSRS) Reflux score, Psychological General Well-Being Index, and Short-Form
      36 Health Survey administered at baseline and 2, 4, 12, and 24 weeks. Medical
      resource use and cost data were collected. RESULTS: More omeprazole-treated
      patients reported improved heartburn resolution at 2 weeks (49.0% vs 33.3%;
      P=.007) and 4 weeks (58.6% vs 35.0%; P<.001) compared with ranitidine-treated
      patients. The GSRS Reflux scores across 3 months showed overall differences
      between omeprazole (mean, 2.67) and ranitidine (mean, 2.95) groups (P=.04). Mean
      total 6-month medical costs were $915 lower ($8371 vs $9286; P=.64), and no
      difference in mean outpatient medical costs ($1198 vs $1158; P=.76) were observed
      in the omeprazole group compared with the ranitidine group. A post hoc secondary
      analysis showed that, at 12 and 24 weeks, patients treated with omeprazole for 8
      weeks or more reported greater heartburn resolution (ie, 24 [43%] of 56 patients
      at both intervals) than patients treated with ranitidine for 8 weeks or more (12
      [24%] and 13 [26%] of 50 patients, respectively; P=.001). CONCLUSIONS: Ranitidine
      and omeprazole were both effective at improving heartburn symptoms; however,
      omeprazole provided greater resolution of heartburn symptoms at 2 and 4 weeks.
      Despite omeprazole's higher acquisition cost, there were no significant
      differences in total or outpatient costs between groups.

PMID- 10910312
TI  - Emergency contraception.
AB  - Emergency contraception is used after unprotected intercourse or a contraceptive
      accident to prevent unwanted pregnancy. It is thought to work by stopping or
      delaying ovulation or preventing implantation if fertilization has already taken
      place. Hormonal methods, mifepristone, and intrauterine device insertion are
      among the methods used worldwide. Combination estrogen-progestin birth control
      pills are the most commonly used form of emergency contraception in the United
      States. According to the Yuzpe method, combination pills are taken within 72
      hours after intercourse, followed by a second identical dose 12 hours later. With
      this method, the number of unintended pregnancies is reduced by about 75%. Nausea
      and vomiting are the most troublesome adverse effects, but these can be
      controlled with antiemetic medication taken prior to the first dose. The Food and
      Drug Administration, Washington, DC, has approved an emergency contraception kit
      consisting of 4 combination pills, a urine pregnancy test, and a patient
      information book. Most recently, the Food and Drug Administration has approved a
      progestin-only formulation, which has fewer adverse effects and equal or improved
      efficacy compared with the combination formula. An intrauterine device can be
      inserted up to 5 days after unprotected intercourse and is a cost-effective
      option if it is used as ongoing contraceptive protection. The most readily
      available form of emergency contraception consists of 2 doses of estrogen
      progestin combination birth control pills or 2 levonorgestrel pills taken 12
      hours apart. Emergency contraception should not be considered as an alternative
      to ongoing contraceptive methods, but can prevent unwanted pregnancy.

PMID- 10910313
TI  - Bacterial vaginosis and treatment of sexual partners.

PMID- 10910314
TI  - Amylophagia presenting as gestational diabetes.
AB  - Amylophagia, or the practice of consuming purified starch, is a particular
      expression of the more general phenomenon of pica. This compulsive dietary
      aberration, observed in many pregnant patients worldwide, is common among rural
      African American women in the southern United States. The effect this practice
      has on the course of gestational diabetes has not been examined. We report 2
      cases of gestational diabetes, refractory to initial dietary management, in which
      the patients were consuming one-half to 1 box of cornstarch per day. Following
      cessation of amylophagia, the gestational hyperglycemia spontaneously resolved.
      Amylophagia is a complex behavioral phenomenon arising from the interplay of
      biochemical, hematological, psychological, and cultural factors. In some patient
      populations, it may represent an often overlooked etiologic or exacerbating
      factor in the condition of gestational diabetes. Family physicians practicing
      obstetrics should inquire about amylophagia in patients who are at risk for this
      behavior and in patients who present with gestational hyperglycemia.

PMID- 10910315
TI  - Pyomyositis in a 5-year-old child.
AB  - We present a case of pyomyositis in an otherwise healthy 5-year-old child that
      underscores the potential for serious, life-threatening complications.
      Pyomyositis of the gluteal, psoas, and iliacus muscles was associated with
      osteomyelitis, septic arthritis, a large inferior vena cava thrombus, septic
      pulmonary emboli, and eventual pneumonia. Primary pyomyositis is a purulent
      infection of striated muscle thought to be caused by seeding from a transient
      bacteremia. The focal infection typically forms an abscess that generally
      responds to intravenous antibiotics and occasionally requires adjunctive computed
      tomography-guided aspiration and drainage. This localized infectious process
      rarely produces further sequelae unless treatment is delayed. Pyomyositis is rare
      in healthy individuals and requires a high clinical suspicion in patients who
      present with fever, leukocytosis, and localized pain.

PMID- 10910316
TI  - Pilagra.

PMID- 10910317
TI  - A health warning on bioterrorism.

PMID- 10910318
TI  - Genome sequencing for all.

PMID- 10910319
TI  - German agencies sound alarm on risks of broad gene patents...as spending goes up
      for research.

PMID- 10910320
TI  - Internet publishing camps renew hostilities.

PMID- 10910321
TI  - US scientists seek more funds for high-tech equipment.

PMID- 10910322
TI  - Mbeki gives AIDS scientists the cold shoulder.

PMID- 10910323
TI  - UK studentships get funding boost.

PMID- 10910324
TI  - Tangled tale of a lost, stolen and disputed coelacanth.

PMID- 10910325
TI  - Sweden streamlines research administration.

PMID- 10910326
TI  - Scientists back GM for Third World.

PMID- 10910328
TI  - Landsat reveals China's farmland reserves, but they're vanishing fast

PMID- 10910327
TI  - Chemistry meets computing.

PMID- 10910329
TI  - Please don't downgrade the sequencers' role..

PMID- 10910331
TI  - The search continues for Karman's St Christopher

PMID- 10910330
TI  - When public-interest science needs solidarity.

PMID- 10910333
TI  - The Oort crowd

PMID- 10910332
TI  - The structure of matter

PMID- 10910335
TI  - The smallest random laser

PMID- 10910334
TI  - Segmentation in silico.

PMID- 10910336
TI  - Apoptosis. The little devil of death.

PMID- 10910337
TI  - Rock signature from the sky

PMID- 10910339
TI  - Pulsar astronomy. Older than they look

PMID- 10910338
TI  - One-hit neuronal death.

PMID- 10910340
TI  - Plant pathology. The bugs from Brazil.

PMID- 10910341
TI  - Developmental biology. Bringing two hearts together.

PMID- 10910342
TI  - A self-extending paediatric leg implant.

PMID- 10910343
TI  - Preventing cyanide release from leaves.

PMID- 10910344
TI  - A triclosan-resistant bacterial enzyme.

PMID- 10910345
TI  - Materials science. Diffusion of a polymer 'pancake'

PMID- 10910346
TI  - Transcranial magnetic stimulation and the human brain.
AB  - Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non
      invasive tool for studying the human brain. A pulsed magnetic field creates
      current flow in the brain and can temporarily excite or inhibit specific areas.
      TMS of motor cortex can produce a muscle twitch or block movement; TMS of
      occipital cortex can produce visual phosphenes or scotomas. TMS can also alter
      the functioning of the brain beyond the time of stimulation, offering potential
      for therapy.

PMID- 10910348
TI  - A large age for the pulsar B1757-24 from an upper limit on its proper motion
AB  - The 'characteristic age' of a pulsar is usually considered to approximate its
      true age, but this assumption has led to some puzzling results, including the
      fact that many pulsars with small characteristic ages have no associated
      supernova remnants. The pulsar B1757-24 is located just outside the edge of a
      supernova remnant; the properties of the system indicate that the pulsar was born
      at the centre of the remnant with a substantial velocity, and that it has
      subsequently overtaken the expanding blast wave. With a characteristic age of
      16,000 yr, the pulsar is expected to have a proper motion of 63-80
      milliarcseconds (mas) per year. Here we report observations of the nebula
      surrounding the pulsar, which limit its proper motion to less than 25 mas yr(-1),
      implying a minimum age of 39,000 yr. A more detailed analysis argues that the
      true age may be as great as 170,000 yr, which is significantly larger than the
      characteristic age. We conclude from this result and other discrepancies
      associated with pulsars that characteristic ages greatly underestimate the true
      ages of pulsars.

PMID- 10910349
TI  - Realignment of the flux-line lattice by a change in the symmetry of
      superconductivity in UPt3
AB  - In 1957, Abrikosov described how quanta of magnetic flux enter the interior of a
      bulk type II superconductor. It was subsequently predicted that, in an isotropic
      superconductor, the repulsive forces between the flux lines would cause them to
      order in two dimensions, forming a hexagonal lattice. Flux-line lattices with
      different geometry can also be found in conventional (type II) superconductors;
      however, the ideal hexagonal lattice structure should always occur when the
      magnetic field is applied along a hexagonal crystal direction. Here we report
      measurements of the orientation of the flux-line lattice in the heavy-fermion
      superconductor UPt3, for this special case. As the temperature is increased, the
      hexagonal lattice, which is initially aligned along the crystal symmetry
      directions, realigns itself with the anisotropic superconducting gap. The
      superconductivity in UPt3 is unusual (even compared to unconventional oxide
      superconductors) because the superconducting gap has a lower rotational symmetry
      than the crystal structure. This special feature enables our data to demonstrate
      clearly the link between the microscopic symmetry of the superconductivity and
      the mesoscopic physics of the flux-line lattice. Moreover, our observations
      provide a stringent test of the theoretical description of the unconventional
      superconductivity in UPt3.

PMID- 10910350
TI  - Shaped-pulse optimization of coherent emission of high-harmonic soft X-rays
AB  - When an intense laser pulse is focused into a gas, the light-atom interaction
      that occurs as atoms are ionized results in an extremely nonlinear optical
      process--the generation of high harmonics of the driving laser frequency.
      Harmonics that extend up to orders of about 300 have been reported, some
      corresponding to photon energies in excess of 500 eV. Because this technique is
      simple to implement and generates coherent, laser-like, soft X-ray beams, it is
      currently being developed for applications in science and technology; these
      include probing the dynamics in chemical and materials systems and imaging. Here
      we report that by carefully tailoring the shapes of intense light pulses, we can
      control the interaction of light with an atom during ionization, improving the
      efficiency of X-ray generation by an order of magnitude. We demonstrate that it
      is possible to tune the spectral characteristics of the emitted radiation, and to
      steer the interaction between different orders of nonlinear processes.

PMID- 10910347
TI  - The genome sequence of the plant pathogen Xylella fastidiosa. The Xylella
      fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis.
AB  - Xylella fastidiosa is a fastidious, xylem-limited bacterium that causes a range
      of economically important plant diseases. Here we report the complete genome
      sequence of X. fastidiosa clone 9a5c, which causes citrus variegated chlorosis--a
      serious disease of orange trees. The genome comprises a 52.7% GC-rich 2,679,305
      base-pair (bp) circular chromosome and two plasmids of 51,158 bp and 1,285 bp. We
      can assign putative functions to 47% of the 2,904 predicted coding regions.
      Efficient metabolic functions are predicted, with sugars as the principal energy
      and carbon source, supporting existence in the nutrient-poor xylem sap. The
      mechanisms associated with pathogenicity and virulence involve toxins,
      antibiotics and ion sequestration systems, as well as bacterium-bacterium and
      bacterium-host interactions mediated by a range of proteins. Orthologues of some
      of these proteins have only been identified in animal and human pathogens; their
      presence in X. fastidiosa indicates that the molecular basis for bacterial
      pathogenicity is both conserved and independent of host. At least 83 genes are
      bacteriophage-derived and include virulence-associated genes from other bacteria,
      providing direct evidence of phage-mediated horizontal gene transfer.

PMID- 10910351
TI  - Configurational entropy and diffusivity of supercooled water
AB  - As a liquid approaches the glass transition, its properties are dominated by
      local potential minima in its energy landscape. The liquid experiences localized
      vibrations in the basins of attraction surrounding the minima, and rearranges via
      relatively infrequent inter-basin jumps. As a result, the liquid dynamics at low
      temperature are related to the system's exploration of its own configuration
      space. The 'thermodynamic approach' to the glass transition considers the
      reduction in configuration space explored as the system cools, and predicts that
      the configurational entropy (a measure of the number of local potential energy
      minima sampled by the liquid) is related to the diffusion constant. Here we
      report a stringent test of the thermodynamic approach for liquid water (a
      convenient system to study because of an anomalous pressure dependence in the
      diffusion constant). We calculate the configurational entropy at points spanning
      a large region of the temperature-density plane, using a model that reproduces
      the dynamical anomalies of liquid water. We find that the thermodynamic approach
      can be used to understand the characteristic dynamic anomalies, and that the
      diffusive dynamics are governed by the configurational entropy. Our results
      indicate that the thermodynamic approach might be extended to predict the
      dynamical behaviour of supercooled liquids in general.

PMID- 10910352
TI  - Electronic connection to the interior of a mesoporous insulator with nanowires of
      crystalline RuO2
AB  - Highly porous materials such as mesoporous oxides are of technological interest
      for catalytic, sensing and remediation applications: the mesopores (of size 2-50
      nm) permit ingress by molecules and guests that are physically excluded from
      microporous materials. Connecting the interior of porous materials with a
      nanoscale or 'molecular' wire would allow the direct electronic control (and
      monitoring) of chemical reactions and the creation of nanostructures for high
      density electronic materials. The challenge is to create an electronic pathway
      (that is, a wire) within a mesoporous platform without greatly occluding its free
      volume and reactive surface area. Here we report the synthesis of an
      electronically conductive mesoporous composite--by the cryogenic decomposition of
      RuO4--on the nanoscale network of a partially densified silica aerogel. The
      composite consists of a three-dimensional web of interconnected (approximately 4
      nm in diameter) crystallites of RuO2, supported conformally on the nanoscopic
      silica network. The resulting monolithic (RuO2//SiO2) composite retains the free
      volume of the aerogel and exhibits pure electronic conductivity. In addition to
      acting as a wired mesoporous platform, the RuO2-wired silica aerogel behaves as a
      porous catalytic electrode for the oxidation of chloride to molecular chlorine.

PMID- 10910353
TI  - Determining the temperature of petroleum formation from the kinetic properties of
      petroleum asphaltenes
AB  - Knowledge of the timing and location of petroleum formation is important in
      assessing the extent of available reserves in hydrocarbon-forming basins. This
      can be predicted from the thermal history of a basin and the kinetic parameters
      that characterize the thermal breakdown of kerogen in source rocks. At present,
      the kinetic parameters of kerogen breakdown are experimentally determined using
      immature rock samples from basin margins, but questions remain about the accuracy
      of this approach, especially when significant variability is observed within
      individual source units. Here we show that the kinetics of hydrocarbon generation
      from petroleum asphaltenes can be used to determine the temperature conditions of
      the actual source rock at the time of expulsion of the sampled petroleum. This
      relationship reflects the structural similarity of asphaltenes to the parent
      kerogen. We expect that our approach may be used as a comparatively simple
      alternative method for assessing the petroleum generation characteristics of a
      given basin, which will allow for better estimates of the available oil resources
      and the risks associated with their exploration.

PMID- 10910354
TI  - Anomalous 17O compositions in massive sulphate deposits on the Earth
AB  - The variation of delta 18O that results from nearly all physical, biological and
      chemical processes on the Earth is approximately twice as large as the variation
      of delta 17O. This so-called 'mass-dependent' fractionation is well documented in
      terrestrial minerals. Evidence for 'mass-independent' fractionation (delta 17O = 
      delta 17O-0.52 delta 18O), where deviation from this tight relationship occurs,
      has so far been found only in meteoritic material and a few terrestrial
      atmospheric substances. In the rock record it is thought that oxygen isotopes
      have followed a mass-dependent relationship for at least the past 3.7 billion
      years, and no exception to this has been encountered for terrestrial solids.
      Here, however, we report oxygen-isotope values of two massive sulphate mineral
      deposits, which formed in surface environments on the Earth but show large
      isotopic anomalies (delta 17O up to 4.6%). These massive sulphate deposits are
      gypcretes from the central Namib Desert and the sulphate-bearing Miocene volcanic
      ash-beds in North America. The source of this isotope anomaly might be related to
      sulphur oxidation reactions in the atmosphere and therefore enable tracing of
      such oxidation. These findings also support the possibility of a chemical origin
      of variable isotope anomalies on other planets, such as Mars.

PMID- 10910355
TI  - Determining multiple length scales in rocks
AB  - Carbonate reservoirs in the Middle East are believed to contain about half of the
      world's oil. The processes of sedimentation and diagenesis produce in carbonate
      rocks microporous grains and a wide range of pore sizes, resulting in a complex
      spatial distribution of pores and pore connectivity. This heterogeneity makes it
      difficult to determine by conventional techniques the characteristic pore-length
      scales, which control fluid transport properties. Here we present a bulk
      measurement technique that is nondestructive and capable of extracting multiple
      length scales from carbonate rocks. The technique uses nuclear magnetic resonance
      to exploit the spatially varying magnetic field inside the pore space itself--a
      'fingerprint' of the pore structure. We found three primary length scales (1-100
      microm) in the Middle-East carbonate rocks and determined that the pores are well
      connected and spatially mixed. Such information is critical for reliably
      estimating the amount of capillary-bound water in the rock, which is important
      for efficient oil production. This method might also be used to complement other
      techniques for the study of shaly sand reservoirs and compartmentalization in
      cells and tissues.

PMID- 10910356
TI  - Cadmium toxicity among wildlife in the Colorado Rocky Mountains.
AB  - Cadmium is known to be both extremely toxic and ubiquitous in natural
      environments. It occurs in almost all soils, surface waters and plants, and it is
      readily mobilized by human activities such as mining. As a result, cadmium has
      been named as a potential health threat to wildlife species; however, because it
      exists most commonly in the environment as a trace constituent, reported
      incidences of cadmium toxicity are rare. Here we have measured trace metals in
      the food web and tissues of white-tailed ptarmigan (Lagopus leucurus) in
      Colorado. Our results suggest that cadmium toxicity may be more common among
      natural populations of vertebrates than has been appreciated to date and that
      cadmium toxicity may often go undetected or unrecognized. In addition, our
      research shows that ingestion of even trace quantities of cadmium can influence
      not only the physiology and health of individual organisms, but also the
      demographics and the distribution of species.

PMID- 10910357
TI  - Competition induces adaptive shifts in caste ratios of a polyembryonic wasp.
AB  - An important transition in insect life-history evolution was the shift from a
      solitary existence to living in groups comprising specialized castes. Caste
      forming species produce some individuals that reproduce and others with worker
      functions that have few or no offspring. Morphologically specialized castes are
      well known in eusocial species like ants and termites, but castes have also
      evolved in less-studied groups like thrips, aphids and polyembryonic wasps.
      Because selection acts at both the individual and the colony level, ratios of
      investment in different castes are predicted to vary with environmental factors
      like competition and resources. However, experimental evidence for adaptive
      shifts in caste ratios is limited owing to the experimental difficulty of
      manipulating factors thought to influence caste ratios, and because some species
      produce behaviourally flexible castes that switch tasks in response to colony
      needs. Unlike other caste-forming species, the broods of polyembryonic wasps
      develop clonally, so that increased production of one caste probably results in
      decreased production of the other. Here we show that the polyembryonic wasp
      Copidosoma floridanum alters caste ratios in response to interspecific
      competition. Our results reveal a distinct trade-off by C. floridanum between
      reproduction and defence, and show experimentally that caste ratios shift in an
      adaptive manner.

PMID- 10910358
TI  - Condition-dependent signalling of genetic variation in stalk-eyed flies.
AB  - Handicap models of sexual selection predict that male sexual ornaments have
      strong condition-dependent expression and this allows females to evaluate male
      genetic quality. A number of previous experiments have demonstrated heightened
      condition-dependence of sexual ornaments in response to environmental stress.
      Here we show that genetic variation underlies the response to environmental
      stress (variable food quality) of a sexual ornament (male eye span) in the stalk
      eyed fly Cyrtodiopsis dalmanni. Some male genotypes develop large eye span under
      all conditions, whereas other genotypes progressively reduce eye span as
      conditions deteriorate. Several non-sexual traits (female eye span, male and
      female wing length) also show genetic variation in condition-dependent
      expression, but their genetic response is entirely explained by scaling with body
      size. In contrast, the male sexual ornament still reveals genetic variation in
      the response to environmental stress after accounting for differences in body
      size. These results strongly support the hypothesis that female mate choice
      yields genetic benefits for offspring.

PMID- 10910359
TI  - The segment polarity network is a robust developmental module.
AB  - All insects possess homologous segments, but segment specification differs
      radically among insect orders. In Drosophila, maternal morphogens control the
      patterned activation of gap genes, which encode transcriptional regulators that
      shape the patterned expression of pair-rule genes. This patterning cascade takes
      place before cellularization. Pair-rule gene products subsequently 'imprint'
      segment polarity genes with reiterated patterns, thus defining the primordial
      segments. This mechanism must be greatly modified in insect groups in which many
      segments emerge only after cellularization. In beetles and parasitic wasps, for
      instance, pair-rule homologues are expressed in patterns consistent with roles
      during segmentation, but these patterns emerge within cellular fields. In
      contrast, although in locusts pair-rule homologues may not control segmentation,
      some segment polarity genes and their interactions are conserved. Perhaps
      segmentation is modular, with each module autonomously expressing a
      characteristic intrinsic behaviour in response to transient stimuli. If so,
      evolution could rearrange inputs to modules without changing their intrinsic
      behaviours. Here we suggest, using computer simulations, that the Drosophila
      segment polarity genes constitute such a module, and that this module is
      resistant to variations in the kinetic constants that govern its behaviour.

PMID- 10910360
TI  - A sphingosine-1-phosphate receptor regulates cell migration during vertebrate
      heart development.
AB  - Coordinated cell migration is essential in many fundamental biological processes
      including embryonic development, organogenesis, wound healing and the immune
      response. During organogenesis, groups of cells are directed to specific
      locations within the embryo. Here we show that the zebrafish miles apart (mil)
      mutation specifically affects the migration of the heart precursors to the
      midline. We found that mutant cells transplanted into a wild-type embryo migrate
      normally and that wild-type cells in a mutant embryo fail to migrate, suggesting
      that mil may be involved in generating an environment permissive for migration.
      We isolated mil by positional cloning and show that it encodes a member of the
      lysosphingolipid G-protein-coupled receptor family. We also show that sphingosine
      1-phosphate is a ligand for Mil, and that it activates several downstream
      signalling events that are not activated by the mutant alleles. These data reveal
      a new role for lysosphingolipids in regulating cell migration during vertebrate
      development and provide the first molecular clues into the fusion of the
      bilateral heart primordia during organogenesis of the heart.

PMID- 10910361
TI  - A one-hit model of cell death in inherited neuronal degenerations.
AB  - In genetic disorders associated with premature neuronal death, symptoms may not
      appear for years or decades. This delay in clinical onset is often assumed to
      reflect the occurrence of age-dependent cumulative damage. For example, it has
      been suggested that oxidative stress disrupts metabolism in neurological
      degenerative disorders by the cumulative damage of essential macromolecules. A
      prediction of the cumulative damage hypothesis is that the probability of cell
      death will increase over time. Here we show in contrast that the kinetics of
      neuronal death in 12 models of photoreceptor degeneration, hippocampal neurons
      undergoing excitotoxic cell death, a mouse model of cerebellar degeneration and
      Parkinson's and Huntington's diseases are all exponential and better explained by
      mathematical models in which the risk of cell death remains constant or decreases
      exponentially with age. These kinetics argue against the cumulative damage
      hypothesis; instead, the time of death of any neuron is random. Our findings are
      most simply accommodated by a 'one-hit' biochemical model in which mutation
      imposes a mutant steady state on the neuron and a single event randomly initiates
      cell death. This model appears to be common to many forms of neurodegeneration
      and has implications for therapeutic strategies.

PMID- 10910362
TI  - Genetic ablation of parathyroid glands reveals another source of parathyroid
      hormone.
AB  - The parathyroid glands are the only known source of circulating parathyroid
      hormone (PTH), which initiates an endocrine cascade that regulates serum calcium
      concentration. Glial cells missing2 (Gcm2), a mouse homologue of Drosophila Gcm,
      is the only transcription factor whose expression is restricted to the
      parathyroid glands. Here we show that Gcm2-deficient mice lack parathyroid glands
      and exhibit a biological hypoparathyroidism, identifying Gcm2 as a master
      regulatory gene of parathyroid gland development. Unlike PTH receptor-deficient
      mice, however, Gcm2-deficient mice are viable and fertile, and have only a mildly
      abnormal bone phenotype. Despite their lack of parathyroid glands, Gcm2-deficient
      mice have PTH serum levels identical to those of wild-type mice, as do
      parathyroidectomized wild-type animals. Expression and ablation studies
      identified the thymus, where Gcm1, another Gcm homologue, is expressed, as the
      additional, downregulatable source of PTH. Thus, Gcm2 deletion uncovers an
      auxiliary mechanism for the regulation of calcium homeostasis in the absence of
      parathyroid glands. We propose that this backup mechanism may be a general
      feature of endocrine regulation.

PMID- 10910364
TI  - PML regulates p53 acetylation and premature senescence induced by oncogenic Ras.
AB  - The tumour suppressor p53 induces cellular senescence in response to oncogenic
      signals. p53 activity is modulated by protein stability and post-translational
      modification, including phosphorylation and acetylation. The mechanism of p53
      activation by oncogenes remains largely unknown. Here we report that the tumour
      suppressor PML regulates the p53 response to oncogenic signals. We found that
      oncogenic Ras upregulates PML expression, and overexpression of PML induces
      senescence in a p53-dependent manner. p53 is acetylated at lysine 382 upon Ras
      expression, an event that is essential for its biological function. Ras induces
      re-localization of p53 and the CBP acetyltransferase within the PML nuclear
      bodies and induces the formation of a trimeric p53-PML-CBP complex. Lastly, Ras
      induced p53 acetylation, p53-CBP complex stabilization and senescence are lost in
      PML-/- fibroblasts. Our data establish a link between PML and p53 and indicate
      that integrity of the PML bodies is required for p53 acetylation and senescence
      upon oncogene expression.

PMID- 10910363
TI  - A cholesteryl ester transfer protein inhibitor attenuates atherosclerosis in
      rabbits.
AB  - Cholesteryl ester transfer protein (CETP) is a plasma protein that mediates the
      exchange of cholesteryl ester in high-density lipoprotein (HDL) for triglyceride
      in very low density lipoprotein (VLDL). This process decreases the level of anti
      atherogenic HDL cholesterol and increases pro-atherogenic VLDL and low density
      lipoprotein (LDL) cholesterol, so CETP is potentially atherogenic. On the other
      hand, CETP could also be anti-atherogenic, because it participates in reverse
      cholesterol transport (transfer of cholesterol from peripheral cells through the
      plasma to the liver). Because the role of CETP in atherosclerosis remains
      unclear, we have attempted to develop a potent and specific CETP inhibitor. Here
      we describe CETP inhibitors that form a disulphide bond with CETP, and present
      one such inhibitor (JTT-705) that increases HDL cholesterol, decreases non-HDL
      cholesterol and inhibits the progression of atherosclerosis in rabbits. Our
      findings indicate that CETP may be atherogenic in vivo and that JTT-705 may be a
      potential anti-atherogenic drug.

PMID- 10910365
TI  - Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage
      response.
AB  - BRCA1 encodes a familial breast cancer suppressor that has a critical role in
      cellular responses to DNA damage. Mouse cells deficient for Brca1 show genetic
      instability, defective G2-M checkpoint control and reduced homologous
      recombination. BRCA1 also directly interacts with proteins of the DNA repair
      machinery and regulates expression of both the p21 and GADD45 genes. However, it
      remains unclear how DNA damage signals are transmitted to modulate the repair
      function of BRCA1. Here we show that the BRCA1-associated protein CtIP becomes
      hyperphosphorylated and dissociated from BRCA1 upon ionizing radiation. This
      phosphorylation event requires the protein kinase (ATM) that is mutated in the
      disease ataxia telangiectasia. ATM phosphorylates CtIP at serine residues 664 and
      745, and mutation of these sites to alanine abrogates the dissociation of BRCA1
      from CtIP, resulting in persistent repression of BRCA1-dependent induction of
      GADD45 upon ionizing radiation. We conclude that ATM, by phosphorylating CtIP
      upon ionizing radiation, may modulate BRCA1-mediated regulation of the DNA damage
      response GADD45 gene, thus providing a potential link between ATM deficiency and
      breast cancer.

PMID- 10910366
TI  - The roles of orthostatic hypotension, orthostatic tachycardia, and subnormal
      erythrocyte volume in the pathogenesis of the chronic fatigue syndrome.
AB  - BACKGROUND: Orthostatic hypotension during upright tilt is an important physical
      disorder in patients with chronic fatigue syndrome. We have tested its occurrence
      during prolonged standing, whether it is correctable, and whether reduced
      circulating erythrocyte volume is present. METHODS: Fifteen patients were
      randomly selected from a large population of patients with chronic fatigue
      syndrome, studied, and observed for several years (by DSB). Blood pressure (BP)
      and heart rate (HR) measured with Dinamap every minute for 30 minutes supine and
      60 minutes standing were compared with these findings in 15 healthy age- and
      gender-matched control subjects and later during lower body compression with
      military antishock trousers (MAST). Plasma catecholamines and circulating
      erythrocyte and plasma volumes were also measured by isotopic dilution methods.
      RESULTS: Abnormal findings in the patients included excessive orthostatic
      reductions in systolic (P < 0.001) and diastolic BP (P < 0.001) and excessive
      orthostatic tachycardia (P < 0.01), together with presyncopal symptoms in 11 of
      the 15 patients and in none of the control subjects after standing for 60 min.
      Lower body compression with the MAST restored all orthostatic measurements to
      normal and overcame presyncopal symptoms within 10 min. Circulating erythrocyte
      but not plasma volumes were subnormal in the 12 women (P < 0.01) and plasma
      norepinephrine concentration rose excessively after standing for 10 min.
      CONCLUSION: Delayed orthostatic hypotension and/or tachycardia caused by
      excessive gravitational venous pooling, which is correctable with external lower
      body compression, together with subnormal circulating erythrocyte volume, are
      very frequent, although not invariably demonstrable, findings in moderate to
      severe chronic fatigue syndrome. When present, they may be involved in its
      pathogenesis.

PMID- 10910367
TI  - Cocaine abuse: repolarization abnormalities and ventricular arrhythmias.
AB  - Increased QT and QT dispersion has been linked to arrhythmic death in patients
      with congenital and acquired long QT syndromes. The repolarization abnormalities
      were studied in 45 patients with a history of chest pain, somnolence, or
      disorientation admitted to the hospital for cocaine abuse. Group I was composed
      of patients with anginal chest pain (n = 23), whereas in group II patients (n =
      22), chest pain was absent. Measurements were made of QT and QTc and of QT and
      QTc dispersion characteristics. Cocaine prolonged the QT, QTc, and QTc dispersion
      and enhanced the appearance of abnormal U waves. Lethal ventricular arrhythmias
      were observed in 3 patients. Anginal chest pain may be a marker for myocardial
      ischemia and, in the presence of abnormal ventricular repolarization, may cause
      lethal ventricular arrhythmias and sudden death in persons exposed to cocaine.

PMID- 10910368
TI  - The association of left ventricular mass with cardiovascular risk factors in
      African American women.
AB  - BACKGROUND: African American women have disproportionately high rates of
      myocardial infarction and stroke. Left ventricular hypertrophy is an independent
      risk factor for cardiovascular disease. Increases in left ventricular mass (LVM)
      may precede the expression of hypertension. The purpose of this study was to
      determine whether LVM is related to cardiovascular risk variables in healthy,
      premenopausal African American women. METHODS: Normotensive or borderline
      hypertensive nondiabetic African American women (N = 52; mean age, 31 years)
      underwent anthropometric and blood pressure measurements, oral glucose tolerance
      test, euglycemic clamp, fasting lipid profile, and two-dimensional
      echocardiography. LVM was calculated by the cube root formula and adjusted for
      height [LVM index (LVMI)]. RESULTS: LVMI correlated with body mass index (r =
      .36, P = 0.009), systolic blood pressure (r = .44, P = 0.001), diastolic blood
      pressure (r = .43, P = 0.002), and central body fat (r = .42, P = 0.002). LVMI
      also directly correlated with lipoprotein (a) (r = .34, P = 0.02). Significant
      independent relationships of other metabolic variables with LVMI were not
      detected. DISCUSSION: These data show that increased LVMI is associated with body
      mass index and central obesity, but not with lipids, insulin resistance, or
      insulin sensitivity. LVMI is also associated with blood pressure before the
      expression of severe hypertension in healthy, premenopausal African American
      women.

PMID- 10910369
TI  - Elevated mortality rates from circulatory disease in African American men and
      women of Los Angeles County, California--a possible genetic susceptibility?
AB  - OBJECTIVE: Reports of higher mortality in African Americans have often focused on
      socioeconomic differences. Such differences do not explain the excess mortality
      in African Americans compared with Hispanics in Los Angeles County. We suggest
      the existence of genetic factors to explain at least some of the differences in
      mortality risk. METHODS: We compared the mortality rates from circulatory
      diseases in African American and Hispanic adults of Los Angeles County for 1988
      to 1992 with the frequency of the angiotensin-converting enzyme (ACE) genotype.
      RESULTS: African American adults 45 to 74 years old had a 2-fold higher overall
      mortality rate than Hispanics. The largest differences were seen for hypertensive
      disease and cardiomyopathy in men; the most striking differences were seen in the
      youngest age group. Rates were lower in women than in men, but African American
      women also showed substantial excess compared with Hispanics. ACE genotype also
      showed a significant difference between the Hispanic and African American
      population; the latter had a significantly higher prevalence of the DD genotype,
      which is associated with a higher level of circulating enzyme, and lower
      prevalence of the II genotype, which is associated with a lower enzyme level.
      CONCLUSION: African American adults aged 45 to 74 years in Los Angeles County
      have a substantial excess mortality from hypertensive diseases compared with a
      similar Hispanic population. The frequency of the ACE DD genotype was higher in
      African Americans than in Hispanics. These studies may indirectly support the
      possibility of a genetic contribution to the excess hypertensive disease
      mortality in African Americans.

PMID- 10910370
TI  - Cardiac and plasma catecholamine responses to exercise in patients with type 2
      diabetes: prognostic implications for cardiac-cerebrovascular events.
AB  - BACKGROUND: Patients with diabetes mellitus have an altered exercise plasma
      catecholamine response, which may be related to the abnormal sympathoadrenal
      function and autonomic neuropathy. Presence of autonomic neuropathy is associated
      with poor prognosis, but relationship between exercise plasma catecholamine and
      prognosis has not been investigated. This study determined if altered plasma
      catecholamine response to exercise was associated with cardiac-cerebrovascular
      events. METHODS: Forty patients with type 2 diabetes without apparent
      macrovascular complications and 30 control subjects performed treadmill exercise
      with serial measurements of plasma norepinephrine and epinephrine. Clinical,
      exercise, and catecholaminergic variables considered relevant to the cardiac
      cerebrovascular events were examined by Cox regression model. Analysis of 24-hour
      heart rate variability was performed in a subgroup of patients. RESULTS: During
      7.2 years, 8 patients, but no control subjects, had events (3 myocardial and 5
      cerebral infarctions). Compared with Event(-) patients, Event(+) patients had:
      (1) orthostatic hypotension; (2) lower peak exercise heart rate; (3) lower plasma
      norepinephrine immediately after exercise; and (4) lower plasma epinephrine at
      peak exercise. High frequency components in heart rate variability analysis were
      diminished in Event(+) patients. Multivariate analysis showed that peak heart
      rate (P = 0.04) and plasma epinephrine at peak exercise (P = 0.03) were
      independent predictors of subsequent events. CONCLUSIONS: These data suggest that
      chronotropic incompetence and lower plasma epinephrine response to exercise are
      associated with high risk of cardiac-cerebrovascular events in patients with type
      2 diabetes.

PMID- 10910371
TI  - Perinatal consequences of maternal-fetal Rh blood group interaction in diabetic
      pregnancy: a nonimmunological perspective.
AB  - BACKGROUND: The recent discoveries about the structure of Rh protein that suggest
      a transport function and the recent observations of a positive correlation
      between Rh(D) protein and glycosylated hemoglobin levels in non-insulin-dependent
      diabetes mellitus prompted us to review our data on diabetic pregnancy to
      evaluate the perinatal consequences of maternal-fetal Rh blood group interactions
      in a metabolic perspective. SUBJECTS AND METHODS: One hundred thirty-two women
      with gestational diabetes and 120 women with preexisting insulin-dependent
      diabetes mellitus were examined. Three hundred eighty-seven consecutive
      nondiabetic puerperae from the same population were considered control subjects.
      RESULTS: In both gestational and insulin-dependent diabetes mellitus, an
      increased proportion of mother Rh(+)/newborn Rh(-) and a decreased proportion of
      mother Rh(-)/newborn Rh(+) joint phenotype has been observed. No deviation has
      been observed for joint phenotypes in which mother and newborn are similar [ie,
      Rh(+)/Rh(+) and Rh(-)/Rh(-)]. In the situation of mother Rh(+)/newborn Rh(-),
      there is a relatively lower rate of fetal loss and a decreased tendency to high
      birth weight. On the contrary, in pairs mother Rh(-)/newborn Rh(+) the fetus
      shows an increase of fetal loss and of tendency to high birth weight.
      CONCLUSIONS: The results are compatible with the hypothesis that when the density
      of Rh protein in the mother is higher than that in the fetus, the conceptus is
      relatively protected against the toxic effect of glucose. In the opposite
      genotypic combination (ie, density of Rh protein higher in the fetus than in the
      mother), the fetus is relatively more susceptible to these effects.

PMID- 10910372
TI  - Healthy patients who perceive poor health: why are they worried sick?
AB  - OBJECTIVE: To explore characteristics of patients who are physically healthy but
      who perceive poor health by investigating the hypothesis that mental health
      problems, financial strain, and deficiencies in social support underlie why these
      patients are "worried sick." METHODS: Three hundred forty-eight continuity
      patients in 2 rural primary care practices were administered the PRIME-MD, the
      MOS SF-36, a health-related worry (1-item, 5-point) scale, the MOS social support
      survey, and perceived economic strain instruments. The patient's physician rated
      physical health on a 10-point scale. Health care utilization was defined as the
      number of office visits and total office and laboratory charges for 6 months
      before and after the interview date. RESULTS: Two hundred thirty-seven patients
      (group A) scored in the upper and middle terciles on the MOS health perceptions
      scale. One hundred eleven patients scored in the lower tercile on health
      perceptions: 59 (group B) were rated as having good physical health (physical
      health rating > 6) and 52 (group C) as having poor health (rating < or = 6). The
      "worried sick" patients (group B) resembled Group A with regard to physical
      health, but resembled the sick (group C) with regard to all MOS functional
      scales, prevalence of mental health diagnoses, and worry. Social support was
      similar across groups. Only 1 of 3 measures of economic strain was less in group
      A than B and C. CONCLUSIONS: Our measures of mental health problems, financial
      strain, and deficiencies in social support accounted only in part for the
      differences among the three groups. Other explanations of why some are "worried
      sick" require study, such as other life stressors and personality traits.

PMID- 10910374
TI  - Doxorubicin-induced cardiomyopathy.

PMID- 10910373
TI  - Chronic rejection of renal transplants: new clinical insights.
AB  - Chronic rejection is the most important cause for returning to dialysis after
      failure of a renal transplant. The term chronic allograft nephropathy refers to
      the progressive decline of renal function seen in some renal transplant
      recipients in association with alloantigen-dependent and alloantigen-independent
      factors. This review examines the role of factors related to allorecognition,
      injury, nephron dosing, and donor and recipient characteristics in the
      development of chronic allograft nephropathy. The clinical associations to
      chronic allograft nephropathy are presented in the context of pathogenetic
      mechanisms of renal damage and disease progression. As there is no therapy
      available at this time for established chronic allograft nephropathy, possible
      areas of intervention for the prevention of chronic rejection are discussed.

PMID- 10910375
TI  - Amiodarone toxicity in a patient with simultaneous involvement of cornea, thyroid
      gland, and lung.
AB  - Amiodarone, an iodine-rich benzofuran derivative, is a highly effective agent for
      the prophylaxis and treatment of cardiac arrhythmias, but it is associated with
      numerous side effects. Amiodarone toxicity involving several organs
      simultaneously has rarely been reported heretofore. In this report, we describe a
      case of a 73-year-old man who developed symptomatic hypothyroidism, pulmonary
      toxicity, and vortex epitheliopathy of the cornea during 6 months of amiodarone
      therapy for frequent palpitation and angina after myocardial infarction. This
      case illustrates that amiodarone may cause toxicity involving several organs
      concurrently in a patient receiving long-term amiodarone therapy. This may be of
      clinical significance in managing such patients.

PMID- 10910376
TI  - Acute, symptomatic atrial fibrillation after sildenafil citrate therapy in a
      patient with hypertrophic obstructive cardiomyopathy.
AB  - This case report describes a patient with hypertrophic cardiomyopathy who
      developed symptomatic atrial fibrillation on two occasions after ingesting
      sildenafil citrate (Viagra). Sildenafil citrate should be withheld or used with
      extreme caution in persons with hypertrophic obstructive cardiomyopathy.

PMID- 10910377
TI  - An uncommon case of fluid retention simulating a congestive heart failure after
      aspirin consumption.
AB  - Nonsteroidal anti-inflammatory drugs are widely used and relatively safe
      medications. We report here an uncommon case of fluid retention simulating acute
      congestive heart failure, secondary to aspirin consumption, promptly reversible
      after discontinuation of therapy, and triggered again by pharmacological
      challenge test.

PMID- 10910378
TI  - Nuclear medicine and radiopharmaceuticals.

PMID- 10910379
TI  - Highlights from WM2K.

PMID- 10910380
TI  - Introduction of the Taylor lecturer.

PMID- 10910381
TI  - The 1999 Lauriston S. Taylor lecture--back to background: natural radiation and
      radioactivity exposed.
AB  - I am profoundly grateful for being chosen as the twenty-third presenter of the
      Lauriston S. Taylor Lecture, and I share this honor with a list of distinguished
      scientists, including my husband, who pay tribute to the premier leader in
      radiation protection. In 1938, Laurie was working for the National Bureau of
      Standards and chaired the Advisory Committee on X-ray and Radium Protection, a
      group of 8 persons, who set the pace for all forthcoming radiation standards. NBS
      had, since 1913, been standardizing essentially all of the radium offered for
      sale in the U.S., and the problem arose to revise the handbook on proper
      conditions for handling radium based on the then current knowledge. This resulted
      in Handbook 23 (1938) superseding the 1934 work. At the time Laurie was a
      scientist working in the measurements side of radiation and though he contributed
      much to that field, his name is inseparably linked with guidance in radiation
      protection. Today we pay tribute for his leadership that he carried out with
      intelligence, grace, and personal warmth. My talk today deals mostly with
      measured data for naturally occurring internal radiation emitters and how these
      data can be used for predictive purposes in estimating the dose and risk from
      internal body contamination. This stresses the "and Measurements" part of the
      Council's title. The topic of this year's NCRP Annual Meeting is "Radiation
      Protection in Medicine: Contemporary Issues." I believe that physicians and State
      and Federal agencies will have to cope with complaints following various exposure
      situations resulting from the cleanup of background radionuclides during closure
      at nuclear facilities, military use of radioactivity, and occurrences of high
      natural background in some locations. They will find comfort in the knowledge
      that existing background radiation data can be the basis for predictions of
      realistic dose and risk in most situations.

PMID- 10910382
TI  - Evaluation of uncertainties in estimates of fetal doses from 59Fe kinetic studies
      at Vanderbilt University.
AB  - In a 1997 paper, Stabin et al. published estimates of the fetal radiation doses
      for women who received oral administrations of 59Fe at Vanderbilt University in
      the 1940's. These authors concluded that there was "considerable uncertainty...
      in the amount of radioactive material administered to these subjects." In an
      effort to quantify this uncertainty, the underlying factors in the input data
      used in the Stabin et al. dose estimates have been examined in detail. Such
      factors include (a) an absence of detailed information on, and discrepancies in,
      the amounts of 59Fe reported to have been administered; (b) the probability that
      the radioactive iron included 55Fe as well as 59Fe; (c) uncertainties as to the
      period of time that elapsed between the administration of the radioiron and the
      taking of the maternal blood samples, and the accompanying impacts of radioactive
      decay; (d) possible losses of 59Fe in the procedures used in preparing the blood
      samples; and (e) questions as to the reported efficiency of the counting
      equipment. Our principal conclusion is that, due to the significant uncertainties
      and the lack of key information, it is not possible to estimate the doses
      accurately. An ancillary conclusion, however, is that the doses were probably
      significantly higher than previously estimated. This latter possibility should be
      carefully considered by any investigators who subsequently seek to use these
      estimates to quantify the relationship between the doses to the fetus and the
      resulting health effects.

PMID- 10910383
TI  - Personnel exposure during gamma endovascular brachytherapy.
AB  - PURPOSE: The use of 192Ir brachytherapy for the treatment of in-stent restenosis
      of the coronary arteries has shown promising clinical results. This paper
      investigates the radiation exposure of catheterization laboratory staff
      associated with the performance of this procedure. METHODS AND MATERIALS: Cath
      lab staff were monitored using personal monitors (shielded against fluoroscopic x
      rays) during the performance of eleven cases using nominal 10 GBq 192Ir sources.
      Staff positions in the lab were simultaneously tracked by video cameras. Direct
      measurements were also made using a survey meter. Treatments were administered in
      a conventional cardiac-catheterization-laboratory. RESULTS: The dosimeter
      readings were analyzed in combination with the radiation survey and time motion
      survey. Brachytherapy procedural times for the cardiologist, oncologist,
      physicist, and angiographic assistants were, respectively, 26 +/- 24, 401 +/-
      132, 486 +/- 148, and 7 +/- 13 s per case (mean +/- standard deviation). Readings
      of the personnel monitors were low. Credible upper limits of the respective doses
      are estimated to be less than 10, 10, 7, and 5 microSv per procedure. Auxiliary
      shields reduced the dose to individuals located outside of the catheterization
      laboratory to less than 0.5 microSv per procedure. CONCLUSIONS: The average
      radiation dose received by laboratory personnel during a representative 192Ir
      endocoronary brachytherapy procedure is estimated to be less than 0.1% of the
      NCRP recommended annual radiation worker's Maximum Permissible Dose (1% of the
      general public's MPD). This level is justifiable as long as the use of 192Ir
      benefits patients by producing an improved clinical outcome relative to the use
      of a less penetrating radionuclide or the application of alternative therapies.
      Further optimization of the delivery procedure is expected to reduce staff dose.

PMID- 10910384
TI  - The impact of plutonium speciation on the distribution coefficients in a sediment
      sea water system, and radiological assessment of doses to humans.
AB  - When radionuclides are released from a source into the marine environment, the
      assessment of long term consequences to humans depends on information on the
      source term, transport in water, interactions with sediments (KD) and biological
      uptake (CF). Sensitivity analysis of assessment models demonstrates that KD is
      one of the most sensitive parameters contributing to large uncertainties in the
      assessment. Furthermore, the interaction of Pu-species with sediments is a time
      and temperature dependent process. The distribution coefficient, Bq kg(-1)
      sediment per Bq L(-1) sea water, increases with time until pseudo
      equilibrium/equilibrium is reached (KD). Thus, the contact time between
      contaminated sea water and sediments should be taken into account in dispersion
      and dose assessment models. In the present work, dynamic tracer experiments have
      been performed where different Pu-species are added to a sediment-sea water
      system to obtain information on KD's. After a defined contact time, the samples
      have been sequentially extracted to determine mobile and bound fractions. The
      results indicate that the distribution coefficient, KD, for plutonium depends on
      Pu-species in question. Thus, sediments act as a sink for Pu(III, IV) (high KD),
      while Pu(III, IV)-organic and Pu(V, VI) should be considered more mobile (low
      KD). Furthermore, the interaction with inert fractions obtained from sequential
      extraction depends less on Pu-species but increase with time. For short time
      interactions, species-specific time functions rather than KD constants should be
      applied in assessment models. When the accepted KD (10(5) L kg(-1)) is
      implemented in the model, the estimated collective dose is about 8 x 10(-4)
      person-Sv, i.e., a factor of about 2 lower than for Pu(III, IV)-organic and Pu(V,
      VI). So changes in KD have an impact on the assessment of collective dose
      received from a potential release of plutonium from fallout, reactor accidents,
      etc., which underlines the need for more detailed studies on speciation,
      kinetics, and KD's in different sediment-sea water systems.

PMID- 10910385
TI  - Long-term trends of radiocesium activity concentrations in vegetation in Irish
      semi-natural ecosystems.
AB  - 137Cs activity concentrations were determined in vegetation from four Irish
      blanket bog ecosystems during the summer months of 1989-1997. The dominant and
      abundant vegetation species were sampled at each site and the data were used to
      estimate long-term trends of 137Cs activity concentrations. A general decline in
      the 137Cs activity concentrations in vegetation was observed from all sites
      sampled. The fastest and most consistent long-term rates of 137Cs decline were
      observed in the bryophyte and lichen vegetation group with 137Cs effective half
      life (T ef) values of 2.2 to 10.7 y. The ericoid group with the exception of one
      case also showed a significant long-term decline in 137Cs activity concentrations
      with T ef values of 3.5 to 12.4 y as did the rush species Juncus squarrosus (T ef
      range 9.3 to 12.8 y). The sedge and grass groups showed the slowest and the least
      consistent rates of 137Cs decline, with T ef values of 2.9 to 59.8 y. Preliminary
      evaluation of 137Cs activity concentrations in sheep from some of the studied
      sites suggests that the decline found in vegetation is reflected in sheep.

PMID- 10910386
TI  - A dosimetric model for inhaled radioactive gases.
AB  - Mathematical simulation models have been used to study transport of insoluble and
      nonreactive gases for more than twenty years. However, gas and vapor transport
      and uptake still are not well understood, and a mathematical model for slightly
      soluble and nonreactive gas transport and uptake still has not been developed.
      This paper describes the development of a mathematical model of diffusion,
      convection, lateral transport into the airway wall, and alveolar absorption for
      inhaled radioactive gases in human conductive and respiratory airways. The model
      is based on a single-path trumpet-bell model. Sensitivity studies were conducted
      to ascertain the influence on the final model of the functional residual
      capacity, the tidal volume and diffusivity and solubility. Results obtained with
      this model are presented for HT gas exposure and are compared with other
      findings. In general, the results obtained in this research are in good agreement
      with other mean experimental results.

PMID- 10910387
TI  - WENDI: an improved neutron rem meter.
AB  - Neutron rem meters are routinely used for real-time field measurements of neutron
      dose equivalent where neutron spectra are unknown or poorly characterized. These
      meters are designed so that their response per unit fluence approximates an
      appropriate fluence-to-dose conversion function. Typically, a polyethylene
      moderator assembly surrounds a thermal neutron detector, such as a BF3 counter
      tube. Internal absorbers may also be used to further fine-tune the detector
      response to the shape of the desired fluence conversion function. Historical
      designs suffer from a number of limitations. Accuracy for some designs is poor at
      intermediate energies (50 keV-250 keV) critical for nuclear power plant
      dosimetry. The well-known Andersson-Braun design suffers from angular dependence
      because of its lack of spherical symmetry. Furthermore, all models using a pure
      polyethylene moderator have no useful high-energy response, which makes them
      inaccurate around high-energy accelerator facilities. This paper describes two
      new neutron rem meter designs with improved accuracy over the energy range from
      thermal to 5 GeV. The Wide Energy Neutron Detection Instrument (WENDI) makes use
      of both neutron generation and absorption to contour the detector response
      function. Tungsten or tungsten carbide (WC) powder is added to a polyethylene
      moderator with the expressed purpose of generating spallation neutrons in
      tungsten nuclei and thus enhance the high-energy response of the meter beyond 8
      MeV. Tungsten's absorption resonance structure below several keV was also found
      to be useful in contouring the meter's response function. The WENDI rem meters
      were designed and optimized using the Los Alamos Monte Carlo codes MCNP, MCNPX,
      and LAHET. A first generation prototype (WENDI-I) was built in 1995 and its
      testing was completed in 1996. This design placed a BF3 counter in the center of
      a spherical moderator assembly, whose outer shell consisted of 30% by weight WC
      in a matrix of polyethylene. A borated silicone rubber (5% boron by weight)
      absorber covered an inner polyethylene sphere to control the meter's response at
      intermediate energies. A second generation design (WENDI-II) was finalized and
      tested in 1999. It further extended the high-energy response beyond 20 MeV,
      increased sensitivity, and greatly facilitated the manufacturing process. A 3He
      counter tube is located in the center of a cylindrical polyethylene moderator
      assembly. Tungsten powder surrounds the counter tube at an inner radius of 4 cm
      and performs the double duty of neutron generation above 8 MeV and absorption
      below several keV. WENDI-II is suitable for field use as a portable rem meter in
      a variety of work place environments, and has been recently commercialized under
      license by Eberline Instruments, Inc. and Ludlum Measurements, Inc. Sensitivity
      is about a factor of 12 higher than that of the Hankins Modified Sphere (Eberline
      NRD meter) in a bare 252Cf field. Additionally, the energy response for WENDI-II
      closely follows the contour of the Ambient Dose Equivalent per unit fluence
      function [H'(10)/phi] above 0.1 MeV. Its energy response at 500 MeV is
      approximately 15 times higher than that of the Hankins and Andersson-Braun
      meters. Measurements of the energy and directional response of the improved meter
      are presented and the measured response function is shown to agree closely with
      the predictions of the Monte Carlo simulations in the range from 0.144 MeV to 19
      MeV.

PMID- 10910389
TI  - Free water 3H concentration in diet samples collected from 1969 to 1988 in Akita,
      Japan.
AB  - Fallout 3H concentrations in diet samples collected from 1969 to 1988 in Akita
      Prefecture are reported. Since the data for samples from the 1960's and 1970's
      are important to understand the long-term movement of 3H in the environment, we
      searched for old diet samples. Recently, diet samples collected in Akita
      Prefecture during 1969-1982 were found and subjected to 3H analysis. The samples
      were originally gathered for nutrition survey programs and had been stored in a
      refrigerated warehouse at -20 degrees C until we located them. The free water 3H
      concentrations in the samples were measured and are reported here. The present
      results are combined with already published data; together they show 3H
      concentrations exponentially decrease from 1969 to 1988 with an apparent half
      time of 5.9 y. Levels of diet free water 3H concentrations are also similar to
      measured and estimated precipitation 3H concentrations in Akita City.

PMID- 10910388
TI  - Radiocesium in children residing in the western districts of the Bryansk Oblast
      from 1991-1996.
AB  - Measurements of 137Cs body burden were carried out in 1991-1996 for children
      residing in the western part of Bryansk Oblast (Russia) where area contamination
      with 137Cs following the Chernobyl accident varied from 0.03-3.7 MBq m(-2). The
      mean and median values of 137Cs specific activity (SA) in the bodies of children
      5-15 y old for the whole period of surveillance averaged for 26,029 measurements
      was 85 Bq kg(-1) and 49 Bq kg(-1), respectively. Mean values in different places
      of residence varied from 30-342 Bq kg(-1) for the settlements where the number of
      examinees was not less than 50. There is a moderately strong relationship between
      mean SA in the settlement and the level of area contamination with 137Cs. A
      strong seasonal effect on 137Cs body burden was found. The ratio of average SA
      values is 1:1.75 for spring to autumn 1992-1995 in the settlement where the
      largest number of children was examined. This effect might be attributed to a
      seasonal change in diet. Based on questionnaire information on individual
      consumption of locally produced foods, the descending rank of contribution of
      food items to 137Cs intake by children was found to be: meat-mushrooms-milk
      vegetables. Assuming that the dose distribution would follow the distribution of
      SA values, internal doses to the whole body from ingested 137Cs were assessed.
      The mean value of annual internal dose averaged for the whole set of measurements
      is 0.21 mSv, and the median of the individual dose distribution is 0.12 mSv y(-1)
      For 2% of the total sample the annual dose exceeded 1 mSv, with the highest
      individual dose being 9 mSv in 1994 for a 7-y-old girl.

PMID- 10910390
TI  - Distribution of natural radioactivity in rocks from Ikogosi-Ekiti, Southwestern
      Nigeria and its radiological implications.
AB  - The natural radioactivity in some rock samples in Ikogosi-Ekiti, Southwestern
      Nigeria, has been measured using a very sensitive gamma spectroscopic system
      consisting of a 76 mm x 76 mm NaI(TI) scintillation detector system coupled to a
      versatile Canberra Series 10 plus multichannel analyzer. The average
      concentrations of natural radioisotopes 238U, 232Th, and 40K are 57.9 +/- 28.1 Bq
      kg-1, 81.6 +/- 23.8 Bq kg(-1) and 1203.1 +/- 687.2 Bq kg(-1), respectively. These
      average values give rise to a mean absorbed dose rate of 0.128 +/- 0.051, microGy
      h(-1) at a height of 1.0 m and an effective dose equivalent of 156.90 microSv (y
      1). The results indicate no radiological anomaly. The data presented here will
      serve as a baseline survey for primordial radionuclide concentrations in rocks of
      the area.

PMID- 10910392
TI  - Does body size contribute to sensitivity of bone tumor induction by radionuclide
      exposure?
AB  - Investigation of a possible increase in sensitivity to occurrence of radionuclide
      induced skeletal malignancy with increasing body size was analyzed among 358
      beagles injected as young adults with either 226Ra or monomeric 239Pu and
      maintained for their lifespans. Corresponding analyses were performed for about
      240 other beagles injected as young adults with 90Sr, 228Ra, or 228Th. Body
      masses at the time of injection ranged between about 5.6 and 16 kg. Logistic
      regression analysis using body mass and cumulative skeletal radiation dose as the
      independent variables indicated that there could not be established a dependency
      of tumor occurrence upon body mass, although skeletal dose was found to be
      significantly correlated with occurrence of bone cancer. Regression analysis
      indicated that for any dosage group there could not be established a correlation
      between body mass and skeletal dose. Each dosage group having similar injected
      kBq kg(-1) for each nuclide was divided into 2 subgroups of equal size, one
      containing the less massive dogs and the other containing the more massive dogs.
      These subgroups within a roughly uniform value of skeletal dose-rate were
      compared by Fisher's Exact Test, and the less massive subgroups were combined
      within each nuclide for an additional, separate analysis against the combined
      more massive subgroups using the same method. In only one instance (the dosage
      group given 3607 kBq 90Sr kg(-1)) was there indicated a substantially greater
      tumor occurrence among dogs in the more massive subgroup (p = 0.061). However,
      for the group given 0.382 kBq 239Pu kg(-1) there was indicated a significant
      difference between subgroups, but the effect was exactly opposite to that found
      for the highest level 90Sr dogs in that the less massive subgroup had a higher
      relative tumor occurrence than the most massive (p = 0.042). For all groups with
      a p-value < 0.10, a possible correlation was investigated between survival and
      body mass at injection (since bone tumor occurrence might be a function of
      longevity), but a significant relationship could not be determined. No
      significant differences could be established between the combined more massive
      and the combined less massive subgroups for any radionuclide. We conclude that,
      for the conditions in our experiment, relative size within a species does not
      contribute importantly to the sensitivity (lifetime occurrence) for induction of
      skeletal malignancy.

PMID- 10910391
TI  - Radium-induced eye melanomas in dogs.
AB  - The intraocular radiotoxicity of intravenously injected 226Ra and 228Ra was
      studied in beagle dogs. Approximately 0.071% of injected radium was retained in
      each eye of beagles following intravenous administration. The retention was
      principally in the tapetum and the intraocular pigmented structures where
      significant pigmentary lesions were produced. These included melanotic plaques on
      the iris, melanosis of the ciliary body, varying degrees of tapetal degeneration,
      and intraocular melanomas. The tumors occurred principally in the ciliary body
      and to a much lesser extent in the iris. They appeared to arise from the pigment
      epithelium layer of the ciliary body. Thus, unlike melanomas arising in other
      sites, they are apparently not of neural crest origin. In addition to bone
      cancer, they represent another radium-induced neoplasm in beagles. Radium-induced
      intraocular melanomas have not been reported in people.

PMID- 10910393
TI  - Chest wall thickness measurements of the LLNL phantom for small area germanium
      detector counting.
AB  - The Lawrence Livermore National Laboratory (LLNL) phantom was developed to
      calibrate lung counting systems that are used to estimate plutonium and other low
      energy photon emitting radionuclides deposited in the lung. Originally, low
      energy photon counting systems consisted of sodium iodide or phoswich detectors,
      but they have been largely replaced by smaller germanium detector arrays. The
      average chest wall thicknesses of the LLNL phantom's torso plate and its overlay
      plates provided by the manufacturer refer to the regions covered by phoswich
      detectors; however, germanium detectors are of a different size and are placed in
      different locations on the phantom's torso plate. Previous work has shown that
      the manufacturer's data were not applicable for large area germanium detectors.
      The lung counting system at the Korea Atomic Energy Institute (KAERI) is a small
      area germanium detector array. Although the detectors are placed within the
      phoswich circles, only about 25% of the area is covered by the detectors. The
      LLNL phantom at KAERI has been examined to determine if the manufacturer's data
      are valid or if new chest wall thickness values must be determined. This paper
      presents chest wall thickness data for the LLNL phantom with and without its B
      series overlay plates at 17 keV, 60 keV, 200 keV, and 1,500 keV and shows that
      these values are different from the manufacturer's values.

PMID- 10910394
TI  - UK report on mobile phones.

PMID- 10910395
TI  - Rutgers University case study: a guide to non-routine high dose rate procedures
      for biomedical facilities.
AB  - Non-routine potentially high dose rate procedures occasionally present themselves
      at biomedical facilities. Lacking significant operational experience, many
      biomedical facilities decide to contract out the work to consulting firms without
      seriously considering doing the work themselves. This study shares the
      University's experiences during a non-routine procedure to extract a 60Co
      irradiation source from an underground storage facility and relocate it to an
      above-ground shielded storage cask.

PMID- 10910397
TI  - Effective dose equivalent estimates in diagnostic radiology with single
      dosimetry.
AB  - In many external exposure situations dose estimates obtained from personal
      monitors significantly overestimate the Effective Dose Equivalent (EDE). This
      occurs particularly when the body is not uniformly exposed due to the irradiation
      conditions or due to protective shielding (i.e., lead apron) of portions of the
      body (NCRP 1995). Many numerical relationships between monitoring data and EDE
      have been proposed to perform more accurate dose estimates (Gill et al. 1980;
      Faulkner and Harrison 1988; Webster 1989; Niklason et al. 1994; Berger et al.
      1995). Also, organizations such as the Conference of Radiation Control Program
      Directors (CRCPD), the National Council on Radiation Protection and Measurements
      (NCRP) and the Electric Power Research Institute (EPRI) have published
      recommendations on this subject (CRCPD 1995; NCRP 1995; EPRI 1998). Before
      implementing the use of any of the proposed relationships, they should be
      thoroughly reviewed so that proper practices are chosen and monitoring data are
      properly evaluated. It is also important for each facility to be aware of the
      regulatory requirements in their state such as if the methodology is approved for
      use, which method and for whom can the EDE be applied. The United States Nuclear
      Regulatory Agency (NRC) does not currently permit dose weighting for any of its
      licensees. The EPRI study performed in 1997 was initiated by the NRC to determine
      how viable dose weighting would be, and for which NRC licensee population. This
      paper discusses numerical relationships for external exposure in diagnostic
      radiology for estimating EDE in a single-monitor program.

PMID- 10910396
TI  - Radiation safety education for laboratory animal science.
AB  - Students enrolled in the laboratory animal science graduate program at MCP
      Hahnemann University seek to gain entrance to veterinary school or to manage an
      animal facility within an academic institution, pharmaceutical or biotechnology
      company conducting biomedical research. Ongoing interaction between faculty in
      the radiation oncology, radiation safety, and lab animal science disciplines
      revealed an acute need for radiation safety education for laboratory animal
      science students who will likely interact with researchers either designing and
      writing protocols for animal studies using radiation or radioactive materials, or
      veterinary staff who will use sources of radiation to diagnose and/or treat
      possible animal injuries and diseases. A core course in the Radiation Sciences
      graduate program was modified to address the needs of these students, instructing
      them in radiation safety, detection and counting instrumentation, and radiation
      biology. These fundamental areas were integrated to help the students gain a
      sound, basic knowledge of radiation and radioactive materials used in biomedical
      research.

PMID- 10910398
TI  - Dose rate limitations of integrating survey meters for diagnostic x-ray surveys.
AB  - Medical and health physicists are often called upon to measure scatter and
      evaluate shielding for diagnostic x-ray installations. As exposure times are
      typically too short to allow rate meters to be successfully used, integrating
      survey meters are often employed. Pressurized survey meters are particularly
      valuable because of their increased sensitivity. In practice, some integrating
      survey meters may give erroneous results under typical measurement conditions.

PMID- 10910399
TI  - Why the radium wasn't found.
AB  - Although this search for lost radium tubes was conducted some forty years ago,
      the lessons deduced in this report are still relevant today. The origin of the
      loss and five stages of the search, which turned out to be unsuccessful, are
      described in detail. These included monitoring the hospital incinerator, its ash,
      residential pathways, the municipal rubbish tip, the hospital theatre and its
      drains, and the hospital environs. Incidentally, the searcher nearly became a
      victim of quicksand, and a false lead was attributed to the use of uranium
      coloring agent in the wall tiles of the hospital theatre. The deduced lessons
      include the necessity for users of sealed radioactive sources to have adequately
      trained staff; to follow an accredited code of practice; to have ready access to
      a radiation survey meter; to have a suitable storage safe and a meticulously
      maintained source register. Some advice is given about the conduct of a search
      and desirable personal attributes of a proficient searcher.

PMID- 10910400
TI  - Experimental incineration of low level radioactive samples.
AB  - To determine the volume reduction potential for incineration of radioactivity in
      low-level radioactive waste, an incineration experiment was performed at the
      Okayama University Radioisotope Center (OURIC). Solid low-level radioactive
      samples (LLRS) were prepared for 15 routinely used radionuclides (45Ca, 1251,
      32p, 33p, 35S, 59Fe, 123I, 131I, 67Ga, 99mTc, 111In, 3H, 14C, 51Cr, and 201Tl).
      For each radionuclide, incinerated one at a time, the smoke duct radioisotope
      concentration was less than 1/10 of the regulatory concentration limit (The
      Japanese law concerning prevention of radiation hazard due to radioisotopes,
      etc.). The radionuclide-containing combustible and semi-combustible LLRS were
      incinerated at the AP-1 50R furnace erected at OURIC, and the distribution of
      radioactivity inside and outside the furnace was measured. In the experimental
      incineration of LLRS containing these 15 radionuclides, the fractions released
      (RF) in the gas phase of the final smoke duct ranged from 0.165 to 0.99. The
      radioactivities remaining in the incineration residue were 99mTc, 87%; 59Fe,
      83.1%; 45Ca, 75%; 51Cr, 62.1%; 33P, 62.0%; 32P, 61.1%; 67Ga, 57.7%; 35S, 26.0%;
      111In, 21.1%; 201Tl, 16.6%; 123I, 11.9%; 131I, 8.2%; 125I, 2.4%; 14C, 0.39%; 3H,
      0.04%. In the incineration of LLR S containing 35S, the rate of adhesion to the
      furnace wall was lower at high-temperature (809 degrees C) incineration than at
      low-temperature (376 degrees C) incineration. For LLRS containing one of the
      three radioiodines, 123I, 125I, or 131I, no such difference was observed between
      low (372 degrees C) and high (827 degrees C) temperature incineration (RF varied
      from 0.82 to 0.94).

PMID- 10910401
TI  - A programmable gas sampler to measure the average radon concentration in a test
      chamber or in the field.
AB  - A Tedlar gas sampling bag was used to retain samples of the test environment of
      interest. Samples, typically hourly, were transferred into a gas sampling bag.
      The volume of each sample was determined by a programmable timer or any computer
      capable of executing a compiled basic program. The program automatically adjusted
      the sample volume of each increment to exactly compensate for radioactive decay
      of radon referred to the end of the exposure period. At that time the radon
      activity collected in the sampling bag was the exact average for the whole
      period. A single Lucas cell was used to report the average concentration for
      typically 2 and 3 day exposures. The results compared with calculated predictions
      and with the average of a series of grab samples taken during the measurement
      period. The benefit of this method was the large work load reduction needed to
      determine the average concentration from a series of grab samples and the ability
      to employ Lucas cells, which are inherently more stable and less expensive than
      active measurement equipment normally used for chamber standardizations.

PMID- 10910402
TI  - Alpha spectormetry measurement reproducibility study for uranium, plutonium, and
      americium in water at Rocky Flats environmental technology site.
AB  - An evaluation of alpha-spectrometry measurement reproducibility of low level
      241Am, 239pU, 238U, and 234U concentrations in surface and ground waters at the
      Rocky Flats Environmental Technology Site was performed using the known and
      measured values of laboratory control samples. Tile purpose of the evaluation was
      to determine the lower limits of reliable quantitative measurement performed on
      recent surface water samples and historic ground water samples using alpha
      spectrometry. At known concentrations between 0.1 and 30 pCi L(-1) (3.7 x 10(-3)
      to 1.11 Bq (L-1)), the reproducibility is dependent on the magnitude of the
      measurement and is quantifiably reproducible to one significant figure.

PMID- 10910403
TI  - Selection of respiratory protection devices for use in very high concentrations
      of airborne plutonium.
AB  - This paper focuses on the proper selection of respiratory protection devices for
      use in very high concentrations of airborne plutonium. Special attention is given
      to the determination of levels at which airborne plutonium presents a hazard that
      is immediately dangerous to life or health.

PMID- 10910404
TI  - State- and sex-specific prevalence of selected characteristics--Behavioral Risk
      Factor Surveillance System, 1996 and 1997.
AB  - PROBLEM/CONDITION: High-risk behaviors (e.g., physical inactivity, cigarette
      smoking, and drinking and driving) and lack of preventive health care (e.g.,
      screening for cancer) are associated with morbidity and mortality from chronic
      disease and injury. The Behavioral Risk Factor Surveillance System (BRFSS)
      collects state-specific information to determine the prevalence of such behaviors
      and preventive practices. By using the BRFSS, states can gain a better
      understanding of the factors that have a major affect on the health of their
      adult populations. The BRFSS is also used to monitor progress toward national
      health objectives. REPORTING PERIOD COVERED: 1996 and 1997. DESCRIPTION OF
      SYSTEM: The BRFSS is a state-based telephone survey of the civilian,
      noninstitutionalized, adult (i.e., persons aged 18 years) population. In both
      1996 and 1997, 50 states, the District of Columbia, and the Commonwealth of
      Puerto Rico participated in the BRFSS. RESULTS: As in previous years, state- and
      sex-specific variations occurred in the prevalence of high-risk behaviors,
      awareness of certain medical conditions, use of preventive health services, and
      health-care coverage. For example, in 1997, the percentage of adults who reported
      being current cigarette smokers ranged from 13.8% to 30.7% among states (median:
      23.2%), and the percentage of adults who reported driving after drinking too much
      alcohol ranged from 0.6% to 5.3% (median: 1.9%). Binge drinking varied
      substantially not only by state (range: 6.3%-23.3%; median: 14.5%) but also by
      sex (men: 22.3%; women: 6.7%). Similarly, the prevalence of overweight varied
      considerably by sex: 62.2% of men and 44.5% of women were overweight in 1997.
      INTERPRETATION: The 1996 and 1997 BRFSS data demonstrate that U.S. adults engage
      in behaviors that are detrimental to their health. The data also demonstrate that
      many adults are making efforts to prevent chronic disease and injury. The
      prevalence of certain behaviors and health practices differs between states and
      between men and women. The reasons for these differences by state and sex are
      subjects for further analysis, but only through continued surveillance can the
      areas that need further study be identified. PUBLIC HEALTH ACTIONS: Data from the
      BRFSS are useful in developing and guiding public health programs and policies.
      For many states, the BRFSS is the only source of state-level data on behaviors
      and practices related to chronic disease and injury; therefore, BRFSS data are
      vital for effective decision-making at the local level. States will continue to
      use these data to help prevent premature morbidity and mortality among their
      adult population and to assess progress toward national health objectives.

PMID- 10910405
TI  - Having your cake (genetically modified) and eating it.

PMID- 10910406
TI  - What factors determine whether individuals found to have hypercholesterolaemia at
      mass screening accept advice to visit their physician.
AB  - OBJECTIVE: This study aims to identify the determinants of compliance with the
      recommendation to visit a physician for advice which was given to individuals
      whose cholesterolemia was > 6.2 mmol/l at mass screening for risk factors of
      cardiovascular diseases. METHODS: Data were collected from 1144 adults found to
      be hypercholesterolemic during a screening programme in 54 work sites and 29
      public areas and contacted by phone two to six months later. Based on the Health
      Belief Model, perceived seriousness, perceived self-efficacy, and cues to action
      were measured. Potential determinants of compliance to the recommendation were
      examined using multivariate analyses. RESULTS: Mean compliance was 58.6%. For the
      perceived seriousness dimension of the Health Belief Model, personal history of
      CVD or risk factors, and prior awareness of cholesterol levels were important
      determinants. Those already treated for hypercholesterolemia comply twice as much
      as those who were aware and untreated. Among cues to action, higher cholesterol
      levels and hypertension are associated with greater compliance; however, smokers
      were less likely to comply. The dimension of perceived self-efficacy, as measured
      by ease of access to health services and prior success in eating habit
      modification, is also associated with compliance to the recommendation.
      Compliance increases significantly with age. For those previously aware of their
      elevated cholesterol level, variables representing perceived self-efficacy were
      no longer determinants. For those previously unaware of their elevated
      cholesterol level, variables representing CVD perceived threat do not influence
      compliance. CONCLUSION: The Health Belief Model appears to be an appropriate
      framework to the determinants of compliance with the recommendation to visit a
      doctor during mass screening.

PMID- 10910407
TI  - Cervical cancer screening: spatial associations of outcome and risk factors in
      Rotterdam.
AB  - OBJECTIVE: Obtaining insight into the geographic distribution of attendance and
      smear test results at the cervical cancer screening program in Rotterdam
      neighbourhoods, associated with socio-economic status, marital status and the
      percentage migrants. DESIGN: Ecological analysis was carried out on data on
      cervical cancer screening outcome and population figures, provided by the
      Rotterdam Local Health Information System, in which health information is
      collected at neighbourhood level. SETTING: The cervical cancer screening program
      in the city of Rotterdam. PARTICIPANTS: Fifty-three neighbourhoods, with overall
      569,105 inhabitants, of whom 70,621 women between 1992 and 1994 were invited for
      the screening program. MAIN RESULTS: Between neighbourhoods a large difference in
      attendance rate and the percentage positive smears exists. A high socio-economic
      level of a neighbourhood, and a low percentage migrants, single or divorced women
      correspond with high attendance. A high socio-economic status of a neighbourhood
      and a low percentage migrants correspond with a low percentage smear test Pap 3B
      or higher. Socio-economic status, percentage migrants and marital status are
      highly interrelated on neighbourhood level. Multivariate analysis showed a
      negative correlation between the attendance rate and the percentage of single and
      divorced women, and a positive correlation between the percentage migrants and
      the percentage of positive smears (Pap 3B or higher). CONCLUSION: Various risk
      groups, showing low attendance or a high percentage of positive smears, are
      clustered in neighbourhoods and can be identified by socio-economic status,
      marital status and nationality. Activities to improve attendance can be focused
      towards these neighbourhoods.

PMID- 10910408
TI  - Reconstructing the life course: health during early old age in a follow-up study
      based on the Boyd Orr cohort.
AB  - A method is described for investigating life course influences on health in early
      old age. The lives of some 300 individuals at present aged 65-75 y have been
      reconstructed from the archived records of a pre-WWII survey, in which they took
      part as children, and from lifegrid interviews with the same individuals 60 y
      later. Despite loss to study at several points those interviewed are shown to be
      representative of the British population socio-demographically, in comparison
      with the 1931 and 1991 decennial censuses, and physically, in comparison with the
      Health Survey for England. Bias is conservative because the most disadvantaged
      were disproportionately affected by loss to follow-up through death and because
      non-responders to interview were more disadvantaged as children than the
      interviewees. Representativeness and conservative bias, it is argued, justify the
      use of these data for investigating life course influences on health in early old
      age.

PMID- 10910409
TI  - Prevention of suicide by youth health care.
AB  - The objective of this study was to examine the effect of freely accessible
      consultation hours in secondary schools by youth health care departments, on
      population rates for suicide and parasuicide. To this end, an ecologic case
      referent study design was used, with data from the Netherlands Bureau of
      Statistics, the National Hospital Discharge Register, the High-School Students
      Study, the youth health care departments in the Netherlands and relevant census.
      Cases were 137 suicide victims aged 15-19 y and 182 12-18 y old subjects admitted
      to hospital because of parasuicide and additionally coded as having had surgery
      as a consequence of the attempted suicide or having a pertinent psychiatric
      disorder. The relevant census in the regions of the participating youth health
      care departments served as referents. The High-School Students Study included
      4997 students aged 12-18 y of which 303 reported having attempted suicide at
      least once. In the ecologic case-referent studies the adjusted Odds Ratio for
      completed suicide in regions with open consultation hours was 0.98 (95% CI 0.69
      1.38) and the weighted Odds Ratio for parasuicide was 1.30 (95% CI 0.97-1.75).
      Analysis of the data of the High-School Students Study resulted in an Odds Ratio
      of 0.96 (95% CI 0.72-1.26). The overall homogeneous Odds Ratio for (para)suicide
      in regions with open consultation hours for all three studies was 1.00 (95% CI
      0.97-1.04); the heterogeneous Odds Ratio was 1.08 (95% CI 0.95 1.09). This study
      does not support the hypothesis that regions, where youth health care departments
      have instituted freely accessible consultation hours in secondary schools, show
      lower rates of suicide or parasuicide compared to regions where no consultation
      hours were implemented.

PMID- 10910410
TI  - Providing welfare rights advice in primary care.
AB  - OBJECTIVE: To evaluate the introduction of dedicated open access welfare rights
      advice sessions in a general practice setting. DESIGN: A retrospective study of
      416 client visits over a 11 month period from August 1995. A prospective
      questionnaire survey of 34 attendees over a three month period from April 1996.
      Semi-structured interviews with 11 involved primary care staff. SETTING: An inner
      city health centre. OUTCOMES: Social characteristics of clients attending;
      problems presented; benefit uptake; views from the health centre staff and
      welfare rights advisers and comments on future development. RESULTS: A total of
      270 new clients used the service during the study period with 146 repeat visits
      (35%). Of the new clients, 158 out of 270 (59%) reported that they were disabled
      and 50% of the 158 had specific disability based welfare rights enquiries. 15% of
      new clients (40 out of 270) were found to be owed money by the current benefit
      system. Of these, 24 clients obtained one-off payments totalling l15,863 and 16
      clients obtained regular payments totalling l539 a week. 58% of interviewed
      clients had not previously accessed any welfare rights advisory services. The
      welfare rights service was considered by the primary health care team to be a
      very useful contribution in a highly deprived area. CONCLUSIONS: The advice
      service increased the uptake of social security benefits in 15% of all new
      attendees. An open access service may not have been the most efficient method of
      delivering such advice. However, the high proportion of new clients who reported
      having a disability suggested that a health centre setting may be particularly
      accessible for those reporting disability. Further work is required to explore
      these findings and the most effective and efficient method of delivering the
      service in a deprived inner city setting.

PMID- 10910411
TI  - They have not heard of AIDS: HIV/AIDS awareness among married women in Bombay.
AB  - Many married women in India have still not heard of AIDS despite increasing
      risks, intensive health education campaigns and widespread scientific and media
      attention. Cross-sectional survey data collected from 350 married women in
      Bombay, India, revealed that one out of three women had not heard of AIDS. The
      women who had not heard of AIDS had significantly fewer years of formal
      education, lower personal and family incomes, less exposure to the mass media and
      were more likely not to know of condoms in comparison to the women who had heard
      of AIDS. The results suggest that there are socio-economic barriers to health
      information. Specific interventions targeted to this group using specific
      channels of communication are urgently needed.

PMID- 10910412
TI  - Tackling the emerging pandemic of non-communicable diseases in sub-Saharan
      Africa: the essential NCD health intervention project.
AB  - There is evidence that the prevalence of certain non-communicable diseases, such
      as diabetes and hypertension, is increasing rapidly in parts of sub-Saharan
      Africa. Others, such as asthma and epilepsy, are known to be common but to be
      poorly managed. This paper describes a project, funded by the Department for
      International Development of the British Government, which aims to provide costed
      and evaluated treatment packages for use at primary health care level, methods
      and materials for evaluating the quality of non-communicable disease care, and a
      protocol for the assessment for national opportunities for the prevention of
      hypertension, heart disease and diabetes. Methods are being developed and piloted
      in urban and rural Tanzania and Cameroon.

PMID- 10910413
TI  - Statement by the Royal Institute of Public Health and Hygiene and Society of
      Public Health on the 'Review of the framework for overseeing developments in
      biotechnology'.

PMID- 10910414
TI  - The future of being old in America: a mental health perspective.

PMID- 10910415
TI  - Personality disorders in elderly patients with dysthymic disorder.
AB  - The authors evaluated personality disorders in elderly patients with DSM-IV
      dysthymic disorder (DD) to identify prevalent personality disorders and their
      clinical correlates. Outpatients (>/=60 years; N=76) with DD were evaluated; most
      were male (65.8%) and had late age at onset (>50 years: 60.5%). Axis II disorders
      were present in 31.2% of patients, with obsessive-compulsive personality disorder
      (OCD; 17.1%) and avoidant personality disorder (11.8%) being the most common.
      Personality disorders were associated with an earlier age at onset of depressive
      illness, greater lifetime history of comorbid Axis I disorders, greater severity
      of depressive symptoms, and lower socioeconomic status. Personality disorders
      occurred in a minority of elderly patients with DD and mainly comprised the
      obsessive-compulsive and avoidant subtypes, similar to reports of personality
      disorders in elderly patients with major depression. In contrast, young adults
      with DD have been shown consistently to have personality disorders at high
      frequency. Together with the predominance of late onset and the lack of
      psychiatric comorbidity, the current findings on personality disorders reinforce
      our view that DD in elderly patients is typically a different disorder from DD in
      young adults.

PMID- 10910416
TI  - A longitudinal study of apolipoprotein-E genotype and depressive symptoms in
      community-dwelling older adults.
AB  - The Apolipoprotein-E (APOE) epsilon 4 allele is a risk factor for Alzheimer's
      disease (AD) and cognitive decline in older adults. Depression may also be a risk
      factor for dementia, and depression is important in the differential diagnosis of
      dementia. The authors performed a 5-year longitudinal study of APOE genotype and
      change in Geriatric Depression Scale scores in 113 community-dwelling older
      adults. No association was observed between APOE genotype and change in
      depressive symptoms. These results do not support the hypothesis that the APOE
      epsilon 4 allele is associated with depression. Important objections have been
      raised to APOE genotyping in the diagnosis of AD. However, the specificity of
      APOE genotyping in AD diagnosis would not appear to be compromised by an
      association with depression.

PMID- 10910417
TI  - Subtypes of cognitive impairment in depressed older adults.
AB  - The authors examined the cognitive profiles of 104 older adults with major
      depression and empirically identified three subgroups with distinct patterns of
      cognitive impairment. The entire sample demonstrated memory impairment relative
      to age-standardized scores, distributed equally across the three cognitive
      subgroups. One-third of subjects displayed either executive impairment or
      attentional deficits. The subgroup with executive dysfunction had greater
      behavioral disability. Identification of executive impairment in depressed older
      adults may facilitate intervention for disturbances in planning, sequencing,
      organizing, and abstracting. Demonstrating the presence of subtypes of cognitive
      impairments in older adults may provide the basis for further investigation of
      mechanisms of late-life depression and the pathophysiology of antidepressant
      response. The association of behavioral disability with executive dysfunction can
      initiate an inquiry into the biology of functional impairment ultimately linking
      biological research to studies of treatment effectiveness.

PMID- 10910418
TI  - The association of demographic factors and physical illness with personality
      change in a community sample of elderly African Americans.
AB  - In a community-based dementia study of African Americans age 65 and older living
      in Indianapolis, key informants were asked to assess the types of personality
      change in all subjects. Information was also collected on demographic factors,
      cognitive functioning, physical well-being, and medical illness. Twenty-nine
      percent of subjects without dementia had reported personality change. Reports of
      personality change were significantly associated with being male, having poor
      daily functioning scores, suffering from physical disability, and having a
      history of cancer.

PMID- 10910419
TI  - Effects of alcohol consumption on the treatment of depression among elderly
      patients.
AB  - The authors examined the effects of alcohol use on the short-term and 3-4-month
      treatment outcomes of patients with late-life depression. Patients (N=2,666) were
      assessed for symptoms of depression, alcohol use, and disability during an
      initial inpatient hospitalization and then 3-4 months postdischarge. Contrary to
      our hypothesis that alcohol consumption imparted a significant additive detriment
      to treatment outcome in patients already suffering from major depression, the
      results suggest that treatment was effective even in those with concomitant use
      of alcohol. Moreover, there appeared to be an added benefit when even modest
      alcohol consumption was decreased among elderly patients suffering from
      depression.

PMID- 10910420
TI  - A retrospective chart review of gabapentin for the treatment of aggressive and
      agitated behavior in patients with dementias.
AB  - In a 24-patient case series from retrospective chart review, the authors examined
      the use of gabapentin for the treatment of aggressive and agitated behaviors in
      nursing home patients with a DSM-IV diagnosis of dementia. On Clinical Global
      Rating Scale scores, 17 of 22 patients were much or greatly improved; 4 were
      minimally improved; and only 1 remained unchanged. Two of the 24 patients
      discontinued use of the medication because of excessive sedation. No other
      significant side effects were noted in treatment lasting up to 2 years.

PMID- 10910422
TI  - Electroconvulsive therapy in old-old patients.
AB  - The authors compared falls, cardiovascular factors, confusion, gastrointestinal,
      pulmonary, and metabolic side effects for "old-old" (>75 years) patient groups
      treated with either electroconvulsive therapy (ECT) or pharmacotherapy. A subset
      of a pharmacotherapy patient group was selected to match for age, sex, and
      diagnosis in a case-control design. Side effects were recorded from each selected
      patient's medical record and compared between groups. Patients receiving ECT
      showed fewer cardiovascular and gastrointestinal side effects. Patients receiving
      ECT had longer lengths of stay and more favorable outcomes. Overall, there was a
      tendency for ECT to result in fewer side effects and better treatment outcomes.
      ECT appears to be relatively safe and more effective than pharmacotherapy for
      major depressive disorders in old-old patients.

PMID- 10910421
TI  - Effect of nortriptyline and paroxetine on extrapyramidal signs and symptoms: A
      prospective double-blind study in depressed elderly patients.
AB  - Selective serotonin-reuptake inhibitors (SSRIs) and tricyclic antidepressants
      (TCAs) have been reported to induce extrapyramidal signs and symptoms (EPS). The
      authors examined the change from baseline EPS, measured by an objective rating
      scale, in a group of elderly depressed patients participating in an ongoing
      randomized, double-blind comparison of nortriptyline and paroxetine. Mild
      baseline EPS were present in both groups. After 6 weeks of antidepressant
      treatment, patients in the nortriptyline group showed a significant decrease in
      total EPS scores. Patients in the paroxetine group showed a similar decrease in
      EPS from baseline, which did not reach statistical significance. There was no
      significant difference between nortriptyline and paroxetine in the change in EPS.

PMID- 10910423
TI  - Functional impairment in older schizophrenic persons. Toward a conceptual model.
AB  - The authors examined the determinants and consequences of impaired functioning in
      older schizophrenic persons by adapting a model of impairment developed by
      Berkman and Gurland. The sample consisted of 117 persons age 55 or older with a
      DSM-III-R diagnosis of schizophrenia. In logistic-regression analysis, the
      overall model attained significance in predicting functional impairment, and
      three predictor variables-abnormal movements, use of antiparkinsonian agents, and
      negative symptoms-attained independent significance. Functional impairment had a
      direct effect on two of the seven resultant variables, community activities and
      self-health, and an indirect effect on two other resultant variables, depression
      and life satisfaction. Thus, the Berkman-Gurland Model has potential usefulness
      for exploring functioning impairment among older schizophrenic persons. Moreover,
      the variables that have the greatest impact on functional impairment are
      potentially remediable.

PMID- 10910425
TI  - Effectiveness of nursing home staff as managers of disruptive behavior:
      perceptions of nursing directors.
AB  - Nursing directors of 899 geographically diverse skilled nursing facilities
      reported substantial limitations in the competence of staff at all levels in
      managing behaviorally disturbed patients and a broad-based need for improvements
      in skills. The authors propose an interdisciplinary team training model as an
      appropriate design for improving competence and promoting collaborative care.

PMID- 10910424
TI  - Weight change in older depressed patients during acute pharmacotherapy with
      paroxetine and nortriptyline: a double-blind randomized trial.
AB  - The authors examined weight change in 32 elderly patients treated for 12 weeks
      with either nortriptyline or paroxetine during acute-phase pharmacotherapy.
      Random assignment to treatment and double-blind assessment of weight change were
      performed, including ascertainment of premorbid (i.e., pre-depression) weight.
      Pretreatment severity of depression was correlated with weight loss during the
      depressive episode and depression-related weight loss, in turn, correlated with
      weight regained during antidepressant treatment. There was no differential weight
      change associated with nortriptyline vs. paroxetine. Rather, subjects in both
      groups approximated their premorbid weights by 12 weeks of acute-phase
      pharmacotherapy with either agent. However, additional investigation of weight
      change during continuation and maintenance pharmacotherapy is necessary and would
      be clinically useful for the long-term management of elderly patients with
      depression.

PMID- 10910426
TI  - Apolipoprotein-E epsilon 4 allele frequency and conferred risk for Cuban
      Americans with Alzheimer's disease.
AB  - The authors compared Apo-E epsilon 4 frequencies for Cuban American and white non
      Hispanic persons with and without Alzheimer's disease (AD). The Apo-E epsilon 4
      allele conferred as large a risk for AD in Cuban Americans as for white non
      Hispanics, a finding that differs from those for Hispanic subjects as a whole.

PMID- 10910427
TI  - Apolipoprotein-E and white-matter hyperintensities in late-life depression.
AB  - The authors conducted a follow-up study of 16 patients with late-life depression
      approximately 6 years after their initial assessment to evaluate the
      relationships between apolipoprotein-E (APO-E) status and white-matter
      hyperintensities (WMH). Ten patients had WMH at baseline, and four patients
      demonstrated an increase in WMH size over time. Three of four patients with the
      APO-E epsilon 4 allele demonstrated an increase in WMH over time, and only 1 of
      12 patients without an epsilon 4 allele had an increase in WMH. Three of four
      patients with APO-E epsilon 4 allele developed a chronic course of major
      depression at follow-up. Patients with APO-E epsilon 4 had a higher number of
      depressive episodes and lower age at onset. APO-E may be a risk factor for
      cerebrovascular disease associated with late-life depression and may affect the
      clinical characteristics and disease course of depression.

PMID- 10910428
TI  - The emerging role of parathyroid hormone-related protein as a renal regulating
      factor.

PMID- 10910429
TI  - Haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura--new insights
      into underlying biochemical mechanisms.

PMID- 10910430
TI  - Leptin and blood pressure--is there a link?

PMID- 10910431
TI  - Should we reduce blood cholesterol to prevent cardiovascular disease among
      patients with chronic renal failure?

PMID- 10910432
TI  - Peritoneal solute transport--we know it is important, but what is it?

PMID- 10910433
TI  - Laparoscopic live-donor nephrectomy.

PMID- 10910434
TI  - Role of reactive oxygen species in glomerulonephritis.

PMID- 10910435
TI  - Progress in dialysis technology: membrane selection and patient outcome.

PMID- 10910436
TI  - Inhibitory effects of rosmarinic acid on the proliferation of cultured murine
      mesangial cells.
AB  - BACKGROUND: Rosmarinic acid is a phenolic compound widely distributed in Labiatae
      herbs such as rosemary, sweet basil, and perilla, which are frequently used with
      meat and fish dishes in Western and Asian countries. In the present study we
      investigated the effects of rosmarinic acid on cultured murine mesangial cell
      proliferation. METHODS: Cultured murine mesangial cells were stimulated by growth
      factors with or without rosmarinic acid, and [(3)H]thymidine incorporation was
      measured in regard both to signal transduction and to cell cycle dependency. In
      other experiments, mRNA extracted from the cells was analysed by Northern
      blotting. RESULTS: Rosmarinic acid inhibited the cell proliferation induced by
      platelet-derived growth factor (PDGF) (P<0.01; IC(50) values, 1.4 microg/ml) or
      tumour necrosis factor-alpha (P<0.01; IC(50) values, 3. 8 microg/ml), and these
      effects involved both the G(0)/G(1) and G(1)/S phases of the cell cycle.
      Rosmarinic acid also suppressed the mRNA expressions of PDGF and c-myc in PDGF
      stimulated mesangial cells. CONCLUSIONS: Rosmarinic acid inhibits cytokine
      induced mesangial cell proliferation and suppresses PDGF and c-myc mRNA
      expression in PDGF-stimulated mesangial cells. Rosmarinic acid in Labiatae herbs
      might be a promising agent to prevent mesangial cell proliferation.

PMID- 10910437
TI  - Interleukin 12 induces crescentic glomerular lesions in a high IgA strain of ddY
      mice, independently of changes in IgA deposition.
AB  - BACKGROUND: Our recently established high immunoglobulin (Ig)A inbred strain
      (HIGA) of ddY mice showed constantly high serum IgA levels, progressive mesangial
      sclerosis accompanied by IgA deposits, and elevated renal expression of
      transforming growth factor (TGF)-beta, mimicking IgA nephropathy. In the present
      study, we assessed the role of the immune system, especially of T cells, in this
      strain. METHODS: The in vitro production of interferon (IFN)-gamma, interleukin
      (IL)-4 and TGF-beta1 by splenic CD4+ T cells was assessed in HIGA mice at 14 and
      28 weeks of age by comparison with age-matched C57BL/6 and BALB/c mice, T-helper
      (Th) 1, and Th2 prone controls respectively. Moreover, recombinant murine IL-12
      was administered intraperitoneally to HIGA mice and serum IgA and renal lesions
      were analysed. RESULTS: The production of IFN-gamma by splenic CD4+ T cells was
      markedly upregulated in HIGA mice at both ages as compared with age-matched
      C57BL/6 and BALB/c mice. Although splenic CD4+ T cells from HIGA mice produced
      less IL-4 than those from BALB/c mice at both ages, the former produced
      significantly more IL-4 with age, which contrasted with the age-associated
      decrease in the latter. Moreover, TGF-beta1 production of these cells in HIGA
      mice was equal to or greater than that in the two groups of control mice at both
      ages. Daily intraperitoneal administration of IL-12 for 1 week significantly
      enhanced crescent formation with glomerular macrophage accumulation and
      interstitial cell infiltration, whereas it reduced the serum IgA level.
      CONCLUSIONS: In HIGA mice, Th1 is markedly upregulated from a young age and there
      is an age-associated Th2 increase with TGF-beta1 upregulation in helper T cells.
      The former may be related to the exacerbation of inflammatory renal lesions on IL
      12 administration, while the latter may contribute to increased IgA production,
      leading to glomerular IgA deposition and progressive glomerulosclerosis in HIGA
      mice. The pathogenic role of T cell function and fluctuation of these subsets,
      especially the Th1/Th2 balance, is crucial to the immunopathological phenotype of
      the renal lesions in HIGA mice.

PMID- 10910438
TI  - Dissociation between urine osmolality and urinary excretion of aquaporin-2 in
      healthy volunteers.
AB  - BACKGROUND: It has been suggested that urinary excretion of the vasopressin
      dependent water channel of the kidney collecting duct, aquaporin-2 (AQP2),
      reflects renal vasopressin action and might be used clinically. It is unclear,
      however, what relation exists between urine osmolality and urinary excretion of
      AQP2 (UAQP2) and it is unknown whether UAQP2 is influenced by hyperosmolality of
      urine or tubular flow rates. METHODS: We measured urine osmolality and UAQP2 in
      healthy volunteers in various conditions: (i) overnight dehydration continued
      during the day, (ii) after infusion of 700 ml hypertonic saline (NaCl 2.5%), and
      (iii) after intranasal administration of 40 microg 1-desamino-8-D-arginine
      vasopressin (DDAVP). The last two tests were performed after water loading. In
      addition, a DDAVP test was performed, after administration of frusemide. RESULTS:
      After overnight dehydration, the urine osmolality increased from 888+/-18 to
      1004+/-17 mosmol/kg during additional hours of thirsting, whereas UAQP2 doubled
      from 140+/-45 to 285+/-63 fmol AQP2/micromol creatinine. Infusion of hypertonic
      saline increased urine osmolality from 70+/-3 to 451+/-68 mosmol/kg, while UAQP2
      remained almost zero. Urine osmolality increased from 101+/-17 to 860+/-30
      mosmol/kg after administration of DDAVP, with a parallel increase in UAQP2 from
      32+/-14 to 394+/-81 fmol AQP2/micromol creatinine. Pre-treatment with frusemide
      attenuated the increase in urine osmolality, but had no effect on UAQP2 after
      DDAVP. CONCLUSIONS: Our data demonstrate that a simple relationship between urine
      osmolality and UAQP2 does not exist. Therefore, random or once-only measurements
      of UAQP2 as an index of renal vasopressin action are not useful. In contrast,
      intranasal application of DDAVP resulted in a parallel rise in urine osmolality
      and UAQP2. Therefore this test might be useful in studying patients with urine
      concentration defects. The DDAVP-frusemide test revealed that the release of AQP2
      into urine is not caused by hypertonicity of tubular fluid.

PMID- 10910439
TI  - Dynamic renal function testing by compartmental analysis: assessment of renal
      functional reserve in essential hypertension.
AB  - BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary
      protein load cause patterns of acute changes in renal function that are
      fundamentally different from changes in normal controls. METHODS: Renal
      clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were
      determined before and after protein ingestion. These tests were performed in
      healthy controls and in patients with essential hypertension (mean arterial
      pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period,
      and after long-term treatment with carvedilol and fosinopril, respectively.
      RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular
      filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two
      tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16
      hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The
      eight patients who were randomized to receive carvedilol improved in their renal
      response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min;
      P=0.04), whereas the eight other patients randomized to receive fosinopril
      exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the
      acute shifts in renal plasma flows were not significant. Mean arterial blood
      pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015).
      CONCLUSIONS: In essential hypertension an acute protein load induces a decrease
      in GFR that may normalize under antihypertensive treatment. The acute changes in
      GFR can be reliably monitored by the here-described compartmental analysis method
      of renal functional reserve.

PMID- 10910440
TI  - Cytokines and T-cell responses in superantigen-related glomerulonephritis
      following methicillin-resistant Staphylococcus aureus infection.
AB  - BACKGROUND: We have previously reported that 10 patients who developed
      glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus
      aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets
      of T cells and in T cells expressing several T-cell receptor (TCR) V beta+cells,
      perhaps representing V beta-specific T-cell activation by MRSA-derived
      superantigens (Kidney Int 1995; 47: 207-216). In this study we examine cytokine
      levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the
      expression of IL-2 receptors in order to better understand the role of bacterial
      superantigens and cytokines in the pathogenesis of MRSA-associated GN. METHODS:
      Twenty-two patients with MRSA infection who later developed GN caused by
      staphylococcal enterotoxin were evaluated immunologically in comparison with
      patients whose MRSA infection was not followed by GN (non-GN group) and normal
      individuals. RESULTS: Among peripheral lymphocytes, the frequency of T cells
      expressing several TCR V betas, especially V beta 5-family TCR, was higher in the
      GN group than in both the non-GN group and the normal healthy control group. GN
      patients also showed increased serum levels of several cytokines, including
      tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-2,
      IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis.
      Memory cells, and IL-2 receptors also were elevated in the GN group. CONCLUSION:
      These results suggest that T cells activated by MRSA-derived staphylococcal
      enterotoxins and subsequent production of cytokines may play an important role in
      the pathogenesis of MRSA-associated GN.

PMID- 10910441
TI  - The protective effect of taurine against gentamicin-induced acute tubular
      necrosis in rats.
AB  - BACKGROUND: Taurine, which is the major intracellular free beta-amino acid, is
      known to be an endogenous antioxidant and a membrane-stabilizing agent. In this
      study, we wished to know whether taurine altered the concentration of gentamicin
      in kidney tissue and could protect against gentamicin-induced acute proximal
      tubular injury. METHODS: Wistar albino rats of both sexes were assigned to three
      groups, which all received one of the following daily intraperitoneal injections
      for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as
      gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone
      (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus
      7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was
      collected for 24 h for the determination of urine volume and creatinine.
      Intracardiac blood was collected for blood urea nitrogen (BUN) and serum
      creatinine determination. The kidneys were removed, weighed, and the left kidneys
      were subjected to biochemical analysis for the determination of thiobarbituric
      acid-reactive substance (TBARS) and lactate levels, and glutathione peroxidase
      (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided
      vertically in half. The upper halves were used for histopathological examination,
      by light and electron microscopy. The lower halves were used to detect the
      gentamicin concentration within the kidney tissue, by high-performance liquid
      chromatography (HPLC). Changes in body weight and normalized kidney weight were
      recorded. RESULTS: Taurine treatment reduced gentamicin-induced increases in
      serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels
      (0.57+/-0.02 vs 1.06+/-0.08 mg/dl, P<0.001; 9.00+/-1.46 vs 20.9+/-2.73 ml,
      P<0.001; 25.3+/-1.87 vs 54.1+/-6.99 mg/dl, P<0. 001; 2.56+/-0.10 vs 3.44+/-0.08
      micromol/g wet tissue, P<0.001; and 66.4+/-3.41 vs 79.5+/-5.07 nmol/g wet tissue,
      P>0.05, respectively). Taurine reduced the accumulation of gentamicin within the
      kidney tissue (233+/-29 vs 494+/-93 microg/g wet tissue, P<0.05). Taurine
      treatment also prevented body weight loss due to gentamicin administration
      (17.8+/-1.64 vs -10.0+/-7.08 g, P<0.01) and normalized reduced Gpx and SOD
      activities (3.46+/-0.16 vs 2.37+/-0. 15 U/g wet tissue, P<0.01; and 15577+/-377
      vs 12662+/-577 U/g wet tissue, P<0.01, respectively). Light microscopic
      examination of the renal tissues from gentamicin-treated rats revealed severe
      histopathological changes, whereas specimens obtained from taurine-treated rats
      revealed only mild changes. This finding was supported by electron microscopic
      examination. CONCLUSIONS: Our observations suggest that taurine treatment
      attenuates the accumulation of gentamicin within kidney tissue and counteracts
      the deleterious effect of gentamicin on renal tubular function. They may have
      potentially important clinical implications.

PMID- 10910442
TI  - Kinetics of carbamylated haemoglobin in acute renal failure.
AB  - BACKGROUND: Carbamylation of proteins by isocyanic acid, the reactive form of
      cyanate derived from urea, is increased in uraemia and may contribute to uraemic
      toxicity. Kinetics of carbamylation that may reflect uraemic toxicity is not
      clearly defined in acute renal failure (ARF). METHODS: Twenty-eight patients with
      ARF and 13 with chronic renal failure (CRF) were included in the study in order
      to determine changes in carbamylated haemoglobin concentration (CarHb) in ARF.
      The usefulness of this parameter for differentiating ARF from CRF was also
      investigated. CarHb was measured by high-performance liquid chromatography after
      acid hydrolysis. RESULTS: Mean CarHb level (expressed as microg carbamyl valine
      per gram (CV/g) Hb) was significantly higher in ARF (54.3+/-5.2) than in normal
      subjects (31.6+/-1.3). On admission, CarHb level was correlated with duration of
      ARF prior to hospitalization in the intensive care unit (r(2)=0.723, P<0.001).
      CarHb was significantly higher at recovery in the subgroup of patients requiring
      haemodialysis than in the subgroup not requiring haemodialysis (82. 4+/-11.3 vs
      46.7+/-5.2, P<0.01). Similarly dialysis patients lost more weight (8.6+/-1.4 vs
      2.7+/-0.5 kg, P<0.005) and had higher averaged blood urea levels in the 20 days
      prior to recovery (17. 6+/-1.9 vs 11.3+/-1.8 mol/l, P<0.05). After recovery,
      CarHb level decreased at a rate of 0.219 microg CV/g Hb per day in patients with
      reversible renal insufficiency. CarHb concentration was higher in patients with
      CRF. A cut-off CarHb value of 100 microg CV/g Hb had a sensitivity of 94% and a
      positive predictive value of 94% for differentiating ARF from CRF. CONCLUSIONS:
      Kinetics of CarHb showed a near normal red blood cell life span in ARF. Changes
      in CarHb enabled, with a good sensitivity, the distinction to be made between
      patients who recovered from ARF and those with sustained renal impairment,
      whether due to prior CRF or resulting from parenchymal sequelae. Measurement of
      CarHb is valuable at clinical presentation of ARF in patients with an unknown
      medical history of renal disease.

PMID- 10910443
TI  - Extended daily veno-venous high-flux haemodialysis in patients with acute renal
      failure and multiple organ dysfunction syndrome using a single path batch
      dialysis system.
AB  - BACKGROUND: In the treatment of acute renal failure in patients with multiple
      organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT)
      are increasingly used because of excellent volume control in the presence of
      improved cardiovascular stability. Patients with MODS, however, are frequently
      catabolic and have a high urea generation rate requiring either cost-intensive
      high-volume CRRT or additional intermittent haemodialysis to provide adequate
      clearance of small-molecular waste products. We tested the closed-loop batch
      haemodialysis system (called Genius((R))) for the treatment of acute renal
      failure in patients with MODS in the intensive care unit. METHODS: Blood flow and
      countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate
      tank of the Genius((R)) system lasts for 18 h of extended single-path high-flux
      haemodialysis (18 h-HFD) using polysulphous F60 S((R)) dialysers. Blood pressure,
      body temperature, and venous blood temperature in the extracorporeal circuit (no
      heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea
      clearance, and total urea removal were monitored. In addition we tested the
      bacteriological quality of the spent dialysate at the end of 18-h treatments.
      RESULTS: Twenty patients with acute renal failure and MODS were investigated.
      Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8
      l/day). Total removal of urea was 14.1+/-6.5 g/day keeping serum levels of urea
      below 13 mmol/l. Mean arterial pressure remained stable during the 18-h
      treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the
      venous blood tubing dropped by 5+/-0.5 degrees C during the 18-h treatment (0.28
      degrees C/h) in the presence of unchanged core temperature in the patients. There
      was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming
      units/ml). CONCLUSIONS: Extended high-flux dialysis using the Genius((R)) system
      combines the benefits of CRRT (good cardiovascular stability, sterile dialysate)
      with the advantages of intermittent dialysis (high urea clearance, low treatment
      costs). High efficiency, simplicity and flexibility of the system offers the
      unique opportunity to use the same dialysis machine for extended time periods (18
      h) as well as for shorter intermittent renal replacement therapy in critically
      ill patients.

PMID- 10910444
TI  - Impaired endothelium-dependent vasodilatation in uraemia.
AB  - BACKGROUND: Patients with chronic renal failure (CRF) have a substantially
      increased risk of cardiovascular death, the proposed mechanisms being arrhythmias
      (left ventricular hypertrophy) and accelerated atherosclerosis. The vascular
      endothelium protects against the development of atherosclerosis principally by
      releasing vasoactive substances such as nitric oxide (NO) and endothelium-derived
      hyperpolarizing factor. In CRF there is accumulation of endogenous inhibitors of
      NO synthesis. In this present study we assessed endothelium-dependent
      vasodilatation in patients with advanced uraemia. METHODS: Sixteen uraemic
      patients (pre-dialysis and continuous ambulatory peritoneal dialysis) and 18
      controls were studied. Forearm plethysmography was used to measure forearm blood
      flow and the changes induced by carbachol (endothelium-dependent vasodilator) and
      sodium nitroprusside (SNP; endothelium-independent vasodilator). The order of
      drugs infused was randomized between subjects. Dose response curves were
      constructed for each agent and area under the curve (AUC) calculated (arbitrary
      units). RESULTS: Overall, vasodilatation to SNP and carbachol was similar between
      uraemic patients and controls. However, it became apparent that there was a
      marked order effect for the drugs infused, such that infusion of SNP as the first
      agent blunted the subsequent response to carbachol. When only those patients and
      controls who received carbachol followed by SNP were studied (10 in each group),
      the response to carbachol in uraemic patients was attenuated compared to
      controls: AUC (median(range)) for uraemic patients 529.0 (150.9-834.7) compared
      to AUC for controls 703.9 (583.5-1576.6); P=0. 028. Vasodilatation to SNP was,
      however, similar between groups: AUC for uraemic patients 1475.0 (857.8-4717.1)
      compared to AUC for controls 1328.1 (216.6-3311.4); P=0.545. CONCLUSIONS: This
      study has demonstrated a marked drug order effect not previously described for
      forearm plethysmography. When the order effect was taken into account, this study
      demonstrated reduced vasodilatation to carbachol in uraemic patients with a
      preserved response to SNP. This pattern indicates impaired endothelium-dependent
      vasodilatation in uraemic patients, a defect that may predispose this group to
      accelerated atherosclerosis.

PMID- 10910445
TI  - [(99m)Tc]-sestamibi parathyroid scintigraphy in chronic haemodialysis patients:
      static and dynamic explorations.
AB  - BACKGROUND: The place of parathyroid gland imaging by [(99m)Tc](technetium)
      sestamibi scintigraphy in uraemic patients with secondary hyperparathyroidism
      remains a matter of debate. The purpose of the present study was (i) to assess
      its value with respect to plasma intact parathyroid hormone (iPTH) levels and to
      surgical parathyroidectomy (PTx), and (ii) to explore the possibility of
      suppressing parathyroid [(99m)Tc]-sestamibi uptake by calcitriol. METHODS: In a
      first cross-sectional, static study 52 chronic haemodialysis (HD) patients with
      plasma iPTH levels between 14 and 2791 pg/ml (normal, 10-65 pg/ml) had a
      [(99m)Tc]-sestamibi scan, and 21 of them underwent surgical PTx. In a second
      longitudinal, dynamic study 14 chronic HD patients with advanced secondary
      hyperparathyroidism received short-term calcitriol treatment in an attempt to
      suppress [(99m)Tc]-sestamibi imaging of parathyroid glands. Calcitriol was given
      intravenously for 2 weeks, 2 microg after each haemodialysis session.
      Scintigraphy was carried out before and at the end of this inhibition test.
      RESULTS: [(99m)Tc]-Sestamibi scan led to imaging of one or more (maximum three)
      parathyroid glands in most, but not all, HD patients with plasma iPTH values >600
      pg/ml. Based on surgical findings, overall sensitivity of [(99m)Tc]-sestamibi
      scan in correctly locating parathyroid glands was only 50%, whereas specificity
      was 100%. In contrast, its sensitivity was 100% in locating single glands in the
      subgroup of five patients with recurrent hyperparathyroidism. The calcitriol
      inhibition test showed suppression of [(99m)Tc]-sestamibi uptake by at least one
      parathyroid gland in eight patients (57%), with complete suppression in five of
      them (36%). Basal plasma iPTH or decrease of plasma iPTH in response to
      calcitriol was not predictive of suppressible [(99m)Tc]-sestamibi uptake in the
      individual case, although mean iPTH was markedly higher in patients with non
      suppressible parathyroid glands. CONCLUSION: Because of its relatively low
      sensitivity the [(99m)Tc]-sestamibi scan is of limited help in the exploration of
      uraemic patients with severe secondary hyperparathyroidism before a first
      surgical PTx. However, it is very useful in locating the remaining parathyroid
      gland(s) in case of reoperation. The novel calcitriol inhibition test of
      [(99m)Tc]-sestamibi uptake could help to better distinguish parathyroid glands
      with non-suppressible, autonomous activity from glands whose activity might be
      amenable to long-term suppression.

PMID- 10910446
TI  - Dialysate related cytokine induction and response to recombinant human
      erythropoietin in haemodialysis patients.
AB  - BACKGROUND: Chronic inflammatory disorders or infections represent a major cause
      of hyporesponsiveness to recombinant human erythropoietin (rHuEpo). To test the
      hypothesis that dialysate-related cytokine induction alters the response to
      rHuEpo, we conducted a prospective study with matched pairs of chronic
      haemodialysis patients. We compared the effect of two dialysis fluids, differing
      in their microbiological quality, on the rHuEpo therapy. METHODS: Thirty male
      patients with end-stage renal disease maintained on regular haemodialysis were
      assigned either to a group treated with conventional (potentially
      microbiologically contaminated) dialysate (group I) or to a group treated with
      online-produced ultrapure dialysate (group II). Randomization was stratified
      according to the maintenance dose of rHuEpo necessary to maintain a target
      haemoglobin level of 10-10.5 g/dl. Patients were followed for 12 months. Kt/V was
      calculated by the formula of Daugirdas. Haemoglobin levels were measured weekly
      and serum ferritin concentrations were determined at 6-week intervals. C-reactive
      protein (CRP) and interleukin-6 (IL-6) was measured by an ELISA at the start of
      the study and after 3, 6 and 12 months. RESULTS: In group I, continuous use of
      bicarbonate dialysate did not change the rHuEpo dosage given to achieve the
      target haemoglobin level and was associated with elevated surrogate markers (CRP,
      IL-6) of cytokine-induced inflammation. The switch from conventional to online
      produced ultrapure dialysate in group II resulted in a lower bacterial
      contamination with a significant decrease of CRP and IL-6 blood levels. It was
      accompanied by a significant and sustained reduction of the rHuEpo dosage, which
      was required to correct the anaemia. Using multiple regression analysis, IL-6
      levels are shown to have a strong predictive value for rHuEpo dosage in both
      groups. CONCLUSIONS: Our data demonstrate that dialysate-related factors such as
      low bacterial contamination can induce the activation of monocytes, resulting in
      elevated serum levels of IL-6. Dialysate-related cytokine induction might
      diminish erythropoiesis. The use of pyrogen free ultrapure dialysate resulted in
      a better response to rHuEpo. Not only would it save money, but it would also help
      to maintain an optimal haemoglobin level without further increase in rHuEpo
      dosage.

PMID- 10910447
TI  - Plasma concentrations of alpha-melanocyte-stimulating hormone are elevated in
      patients on chronic haemodialysis.
AB  - BACKGROUND: Clinical and/or laboratory signs of systemic inflammation occur
      frequently in patients undergoing long-term haemodialysis. It is likely,
      therefore, that a compensatory release of endogenous anti-inflammatory molecules
      occurs to limit host reactions. The aim of the present research was to determine
      if the potent anti-inflammatory peptide alpha-melanocyte-stimulating hormone
      (alpha-MSH), a pro-opiomelanocortin derivative, is increased in plasma of
      haemodialysis patients. Because endotoxin and cytokines induce alpha-MSH in vivo
      and in vitro, we also measured plasma concentrations of endotoxin, interleukin-6
      (IL-6), and tumour necrosis factor alpha (TNF-alpha), and the two circulating
      products of activated monocytes, nitric oxide (NO) and neopterin. METHODS: Thirty
      five chronic haemodialysis patients, 20 patients with chronic renal failure not
      yet on dialysis, and 35 normal controls were included in the study. In the
      haemodialysis group, blood samples were obtained before and at the end of a
      dialysis session. Plasma alpha-MSH was measured using a double antibody
      radioimmunoassay, and IL-6, TNF-alpha, and neopterin using specific enzyme-linked
      immunosorbent assays. Plasma nitrites were determined by a colorimetric method,
      and endotoxin with the quantitative chromogenic LAL (limulus amoebocyte lysate)
      method. RESULTS: Mean plasma alpha-MSH was higher in haemodialysis patients than
      in control subjects, with the peptide concentrations being particularly elevated
      in dialysed patients with detectable endotoxin. High alpha-MSH concentrations
      were observed in the pre-dialysis samples, with no substantial change at the end
      of the dialysis session. Plasma concentrations of IL-6, TNF-alpha, neopterin, and
      NO were generally elevated in chronic haemodialysis patients and there was a
      negative correlation between circulating alpha-MSH and IL-6. In patients with
      renal failure not yet on dialysis, mean plasma alpha-MSH was similar to that of
      normal subjects. CONCLUSIONS: alpha-MSH is increased in the circulation of
      chronic haemodialysis patients and particularly so in case of detectable
      endotoxaemia. Reduction of renal clearance is unlikely to contribute to the
      observed rise of the peptide because alpha-MSH concentration is not increased in
      patients with chronic renal failure who are not yet on dialysis. It is likely
      that dialysis-associated endotoxaemia, directly and/or through cytokine release,
      enhances the production of the anti-inflammatory mediator alpha-MSH that limits
      host reactions.

PMID- 10910448
TI  - T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients.
AB  - BACKGROUND: Patients on chronic intermittent haemodialysis (HD) show an impaired
      cellular and humoral immune response that clinically appears with frequent
      infectious complications and low vaccination responses. This immune defect
      strongly correlates with reduced in vitro proliferative responses of T cells. The
      defect is localized in antigen presenting cells, which show a decreased co
      stimulatory activity. Furthermore, the impaired immune response correlates with
      an increased production of pro-inflammatory cytokines. In response to primary
      activation, CD4 positive T helper (Th) cells mainly differentiate into either Th1
      or Th2 cells. Th1 cells support cell mediated immunity whereas Th2 cells enhance
      humoral immune responses. Since both types of responses mutually inhibit each
      other, the impaired humoral immune response seen in HD patients could either be
      due to a reduced number of Th2 cells or to a predominant Th1 response. METHODS:
      We analysed the Th cell profile in HD patients using flow cytometry. Monocytic
      cytokine expression was analysed using both flow cytometry and enzyme linked
      immunoadsorbant assays. RESULTS: Our data demonstrate that the cytokine
      differentiation profile in circulating T cells from HD patients is dysregulated
      and characterized by an increase in Th1 cells, but a normal amount of Th2 cells.
      Moreover, the skewed helper cell responses correlate with a higher percentage of
      monocytes capable of secreting the Th1 promoting cytokine interleukin 12 (IL-12).
      CONCLUSIONS: Our findings contribute to a better understanding of the
      pathogenesis of impaired cellular immune functions in dialysis patients and, in
      particular, the decreased antibody production after vaccination. They provide a
      link between overproduction of pro-inflammatory cytokines (IL-12) and imbalanced
      T-cell activation.

PMID- 10910449
TI  - L-Arginine-enriched preservation solution decreases ischaemia/reperfusion injury
      in canine kidneys after long-term cold storage.
AB  - BACKGROUND: Kidneys stored hypothermically for transplantation show varying
      degrees of tissue injury, depending on the duration of preservation. The causes
      of injury are not entirely clear. We investigated the quality of renal functional
      recovery in canine kidneys after 72 h hypothermic preservation in custodiol
      solution or custodiol solution plus L-arginine. METHODS: Kidneys obtained from
      mongrel dogs, weighing 18-25 kg, were subjected to 72-h cold ischaemia after
      flushing. Animals were divided into two groups (n=18/group). A flush solution of
      either custodiol solution or custodiol solution plus L-arginine 1 mmol/l was used
      for each group. After 72-h cold storage all animals had a contralateral
      nephrectomy, and autotransplantation was performed to external iliac artery and
      vein. Survivals were evaluated at 3 days. RESULTS: Renal damage was assessed by
      kidney function tests, serum creatinine (SCr), blood urea nitrogen (BUN) and
      light histology. Malondialdehyde (MDA) was measured as an index of lipid
      peroxidation. SCr and BUN (24, 48 and 72 h) were significantly different from the
      control and L-arginine groups. Histological damage was less in the L-arginine
      group. MDA levels were significantly different with the lower levels in the L
      arginine group. CONCLUSIONS: On the basis of these data, we concluded that
      exogenous L-arginine (a substrate for NO synthesis) has a beneficial and
      protective effect on long-term (72 h) hypothermic ischaemical damage in canine
      kidneys.

PMID- 10910450
TI  - Randomized trial of conversion from mycophenolate mofetil to azathioprine 6
      months after renal allograft transplantation.
AB  - BACKGROUND: In the first year after renal allograft transplantation, triple
      therapy immunosuppression with cyclosporin (CsA), prednisone (P), and
      mycophenolate mofetil (MMF) is superior to a triple therapy treatment that
      includes azathioprine (AZA) instead of MMF. Whether long-term treatment with CsA
      P-MMF is better than treatment with CsA-P-AZA is a matter of debate, as 3-year
      graft survival is similar in MMF- and AZA-treated patients. The purpose of the
      present study was to examine the short-term effect of changing MMF to AZA in low
      risk renal allograft recipients 6 months after transplantation. METHOD: This was
      a randomized, open-label single-centre study, recruiting 48 low risk renal
      allograft recipients on CsA-P-MMF therapy 6 months after transplantation,
      comparing the outcome with continued MMF treatment (2 g b.i.d.) (group A, n=22)
      or switching MMF to AZA (1 mg/kg) treatment (group B, n=26). RESULTS: The outcome
      after a 6-months follow-up of patients in group A and group B was similar.
      Treatment failure rates (defined as clinically diagnosed acute rejection
      episodes) were 4.5% in group A and 3.8% in group B. There were no patient deaths
      and no graft failures during the 6-months observation period. Graft function was
      excellent and similar in both groups. CONCLUSION: Replacing MMF with AZA 6 months
      after transplantation in low-risk renal allograft recipients is safe and is not
      associated with altered graft function in the short term.

PMID- 10910451
TI  - Very-long-chain acyl-coenzyme A dehydrogenase deficiency--a new cause of
      myoglobinuric acute renal failure.

PMID- 10910452
TI  - Primary Epstein-Barr virus infection and recurrent type I membranoproliferative
      glomerulonephritis after renal transplantation.

PMID- 10910453
TI  - A case of anti-glomerular basement membrane glomerulonephritis superimposed on
      membranous nephropathy.

PMID- 10910454
TI  - Two renal transplants from one cadaveric donor: one recipient with simultaneous B
      cell lymphoma and Kaposi's sarcoma, and the other with T cell lymphoma.

PMID- 10910455
TI  - The hypertensive young lady with renal cysts--it is not always polycystic kidney
      disease.

PMID- 10910457
TI  - Steinstrasse due to distal renal tubular acidosis with sensorineural deafness.

PMID- 10910456
TI  - Physician-induced hypocalcaemia, nephrocalcinosis, and incomplete distal renal
      tubular acidosis.

PMID- 10910458
TI  - A domestic fight or something else?

PMID- 10910459
TI  - The renal divisions of the medical faculties of gent and heidelberg, with the
      support of fresenius medical care

PMID- 10910460
TI  - Does E/A ratio correctly estimate diastolic dysfunction in patients with chronic
      renal failure?

PMID- 10910461
TI  - Abysmal prognosis with type 2 diabetes entering dialysis.

PMID- 10910462
TI  - Troponin I is a better prognostic parameter of cardiovascular events in
      asymptomatic patients on haemodialysis than troponin T.

PMID- 10910463
TI  - Renal thrombotic microangiopathy, campylobacter gastroenteritis and anti
      cardiolipin antibody.

PMID- 10910464
TI  - Albanian contribution to the treatment of refugee renal patients from Kosovo.

PMID- 10910465
TI  - Tumoural calcinosis associated with subclavian vein occlusion and hypercalcaemia
      in a haemodialysis patient.

PMID- 10910466
TI  - Effect of fish oil in a patient with post-transplantation IgA nephropathy.

PMID- 10910468
TI  - Announcements

PMID- 10910467
TI  - The effect of intradialytic exercise on solute removal.

PMID- 10910469
TI  - Assessing lymphocyte functions in neonates for revealing abnormal prenatal
      development of the immune system.
AB  - Because it is difficult to assess prenatally induced functional deficits of the
      human immune system, we developed an ex vivo method for differentiation and
      maturation of peripheral lymphocytes of newborn, preferentially using umbilical
      cord blood. Many lymphocyte subsets of newborn infants are "immature" with
      respect to defined surface receptors. An example of such an immaturity is the
      almost complete lack of "memory"-type helper T cells (also designated as helper
      inducer cells), characterized by expressing the surface receptors:
      CD4(+)CD45R0(+)CD45RA(-)CD29(high). On the other hand, umbilical cord blood
      contains many "naive"-type helper T cells (often designated as suppressor-inducer
      cells), with the receptors: CD4(+)CD45R0(-)CD45RA(+)CD29(low). In this report, we
      demonstrate that the immature helper lymphocyte population of umbilical cord
      blood is capable of differentiating to mature cells following stimulation with
      pokeweed mitogen (PWM) and other stimulants ex vivo. The obtained receptor
      pattern is virtually indistinguishable from the one observed on the mature cells
      of adults. Such an extensive differentiation can only be achieved with cells of
      newborns. As intermediates during differentiation in culture, CD45R0(+)CD45RA(+)
      cells may be observed which are rather rare in vivo. Additionally, the appearance
      of several activation (CD25, CD69, HLA-DR) and adhesion (CD11a, CD11b, CD11c,
      CD18, CD49b, CD49d, CD54) receptors on CD4 cells were analyzed. With this model
      system evidence for the sequence of events during differentiation and maturation
      may be obtained. This ex vivo-model is capable of studying the capacity of
      lymphocytes for differentiation and activation processes barely accessible in
      vivo. It may also be expected to represent an interesting tool for measuring the
      capacity for maturation and differentiation in the blood of children of different
      ages under normal and pathological conditions ex vivo. In addition, substance
      induced effects may be studied in vitro with this approach on immature cells from
      newborn, or infants during culturing. Teratogenesis Carcinog. Mutagen. 20:171
      193, 2000.

PMID- 10910470
TI  - Metabolic fate of chemical mixtures. I. "Shuttle Oxidant" effect of lipoxygenase
      generated radical of chlorpromazine and related phenothiazines on the oxidation
      of benzidine and other xenobiotics.
AB  - Many carcinogens, mutagens, teratogens, and other toxicants are known to be
      oxidized by lipoxygenases to potentially deleterious free radical intermediates.
      In this study, we tested for the first time the possibility that certain
      efficient substrates for lipoxygenase produce shuttle oxidants that stimulate the
      generation of reactive species from other chemicals. To evaluate the hypothesis,
      we investigated the metabolic interaction of two well-known substrates,
      chlorpromazine and benzidine, which have been shown to be oxidized by soybean
      lipoxygenase in the presence of hydrogen peroxide. The evidence presented here
      clearly indicates that the chlorpromazine cation radical generated by the
      lipoxygenase triggers a rapid oxidation of benzidine to benzidine diimine. Under
      the experimental conditions employed, the metabolic interaction resulted in a 42
      fold stimulation in the rate of benzidine oxidation. The magnitude of stimulation
      of benzidine oxidation exhibited a dependence on the pH of the reaction medium,
      amount of the enzyme, and concentration of chlorpromazine, benzidine, and
      hydrogen peroxide. A number of other phenothiazines were also found to stimulate
      benzidine oxidation, albeit to a lesser degree. The chlorpromazine cation radical
      stimulated the oxidation of all six other xenobiotics tested. The highest
      stimulation (94-fold) was noted with tetramethyl phenylenediamine oxidation to
      the Wursters blue radical, while the lowest stimulatory response (2-fold) was
      observed with guaiacol. Preliminary data suggest that purified human term
      placental lipoxygenase also displays a similar stimulatory response in the
      benzidine oxidation in the presence of chlorpromazine. Although the toxicological
      significance of these in vitro findings remains to be established, it is worth
      pondering whether such a synergistic interaction occurs in humans in vivo.
      Teratogenesis Carcinog. Mutagen. 20:195-208, 2000.

PMID- 10910471
TI  - Phenolphthalein induces chromosome aberrations in human and Chinese hamster liver
      cells (CHEL) cultured in vitro.
AB  - Phenolphthalein is a nonprescription laxative agent that has been widely used
      during this century. Recent studies in animal models have shown that
      phenolphthalein has carcinogenic activity. In order to assess cytogenetic effects
      on human cells in vitro, we tested phenolphthalein in a chromosome aberration
      assay in human embryo cells derived from amniotic fluid. Our results show that
      phenolphthalein induces a significant increase in the frequency of chromosome
      aberrations in human cells. The lowest dose level at which the clastogenic effect
      is evident is 23.2 microg/ml. Similar positive results were obtained in a Chinese
      hamster liver cell line, which is metabolically competent to activate different
      classes of promutagens and procarcinogens into biologically active metabolites.
      Instead, parallel experiments in Chinese hamster ovary cells did not show any
      clastogenic effect due to phenolphthalein. These latter data suggested that
      phenolphthalein acts as a promutagen and must be metabolically activated to exert
      its clastogenic effect. Teratogenesis Carcinog. Mutagen. 20:209-217, 2000.

PMID- 10910472
TI  - Comparative developmental toxicity study of indium in rats and mice.
AB  - The developmental toxicity of indium was examined in both rats and mice using
      comparable experimental protocols. Pregnant rats received a single intravenous
      administration of indium trichloride (InCl(3)) at 0.4 mg In/kg, on day 9, 10, or
      11 of pregnancy and their fetuses were examined on day 20. Pregnant mice were
      treated in the same manner at 0.8 or 1.6 mg In/kg on day 7, 8, or 9 of pregnancy
      and their fetuses were examined on day 18. In rats, indium caused fetal weight
      decrease and fetal gross malformations, such as brachyury, kinked tail, cleft
      palate, and oligodactyly, most severely by the administration on day 10. In mice,
      however, indium did not cause fetal gross malformations, although it caused fetal
      weight decrease at 0.8 mg In/kg or more and fetal death at 1.6 mg In/kg, most
      severely by the administration on day 8. It was concluded from these results that
      rats and mice were susceptible to the embryotoxicity of indium at similar
      developmental stages in the early organogenetic period, but mice were less
      susceptible to the teratogenicity of indium than rats in terms of gross
      malformation. Toxicokinetic factors may be involved in this different
      susceptibility. Teratogenesis Carcinog. Mutagen. 20:219-227, 2000.

PMID- 10910473
TI  - Nongenotoxic (epigenetic) carcinogens: pesticides as an example. A critical
      review.
AB  - The following groups of pesticides are considered in this review by supposed
      mechanisms of their carcinogenicity: hepatocarcinogenic pesticides, pesticides -
      peroxisome proliferators, pesticides as endocrine disruptors, goitrogenic
      pesticides, pesticides producing sustained cell proliferation and some others.
      With very rare exceptions, pesticides do not react with DNA directly and the
      mechanisms of their carcinogenicity are, in general, similar to those of other
      nongenotoxic (epigenetic) carcinogens, namely: promotion of spontaneous
      initiation, cytotoxicity with sustained cell proliferation, oxidative stress,
      formation of activated receptors and some others. Genotoxicity of pesticides
      varies from its complete absence (propiconazol as an example) to a very
      pronounced one (captafol) with remaining compounds in between. These two
      compounds demonstrate full correlation between genotoxicity and carcinogenicity
      (or their absence). Many pesticides give positive results in some tests for
      genotoxicity but these results are frequently controversial, not readily
      reproducible, or obtained only at toxic dose levels. The weak genotoxicity of the
      majority of pesticides is easily explainable by their rather severe testing
      before their introduction into practical use. The above mechanisms are threshold
      based and therefore pesticides are regulated through NOEL/safety factor. There
      exist examples of lack of correlation between genotoxicity and carcinogenicity:
      some pesticides are genotoxic (although not strongly) but noncarcinogenic, others
      are considered as nongenotoxic but are strongly carcinogenic (chlorothalonil,
      acetochlor). The general scheme of the promoters' effect is presented in which an
      important role is attributed to the cytochrome P-450 induction (some pesticides
      are the cytochrome P-450 inducers), formation of reactive oxygen species and
      peroxitome proliferation. Teratogenesis Carcinog. Mutagen. 20:229-240, 2000.

PMID- 10910474
TI  - Genotoxicity of instant coffee and of some phenolic compounds present in coffee
      upon nitrosation.
AB  - Instant coffee exhibits genotoxic activity upon nitrosation at acidic pH values
      in the Ames tester strain TA100. Using adsorption chromatography (Amberlit XAD-2)
      it was observed that the major fraction of molecules responsible for the
      genotoxic activity upon nitrosation was not retained on this resin, suggesting
      that the polar molecules present in instant coffee could be responsible for the
      genotoxicity observed upon nitrosation. Some phenolic molecules present in
      instant coffee (catechol, caffeic acid, and chlorogenic acid) were also genotoxic
      upon nitrosation under the same experimental conditions. The concentrations of
      nitrosatable phenolic compounds in the studied coffee were determined by HPLC and
      their contributions to the total genotoxicity observed were studied. The results
      obtained suggest that besides phenolic compounds other molecules were also
      involved in the genotoxicity of this beverage upon nitrosation. Teratogenesis
      Carcinog. Mutagen. 20:241-249, 2000.

PMID- 10910475
TI  - Intraoperative cerebral arterial embolization during total hip arthroplasty.
AB  - BACKGROUND: Fat embolism to the pulmonary circulation is known to occur during
      total hip arthroplasty, especially during insertion of a cemented femoral
      component. Fat and air bubbles may enter the systemic circulation via a patent
      foramen ovale or through pulmonary circulation. METHODS: To determine whether
      microemboli to the brain were occurring during total hip arthroplasty, 23
      patients underwent transcranial Doppler assessment of emboli to the middle
      cerebral artery during total hip arthroplasty. Surgery was performed with the
      patient in the lateral decubitus position so that the probe recorded from the
      nondependent side. RESULTS: Successful recordings were made in 20 patients, in 8
      of 20 patients there were embolic signals, which ranging from 1 to 200. In all
      eight patients, signals were recorded during impaction of a cemented component or
      after relocation of the hip. Only one patient showed evidence of emboli with
      impaction of the acetabulum component. In two patients there were 150 and 200
      embolic signals: in both mild respiratory symptoms developed. One patient became
      overtly agitated during a flurry of emboli. CONCLUSION: Cerebral microemboli can
      occur during total hip arthroplasty. Whether this contributes to changes in
      postoperative cognitive function is unknown.

PMID- 10910476
TI  - Competence of the internal jugular vein valve is damaged by cannulation and
      catheterization of the internal jugular vein.
AB  - BACKGROUND: Experimental results suggest that the competence of the internal
      jugular vein (IJV) valve may be damaged when the IJV is cannulated for insertion
      of a central venous catheter. It has further been hypothesized that the risk of
      causing incompetence of the proximally located valve might be reduced by using a
      more distal site for venous cannulation. The present study evaluated these
      hypotheses in surgical patients. METHODS: Ninety-one patients without preexisting
      incompetence of the IJV valve were randomly assigned to undergo distal or
      proximal IJV cannulation (> or = 1 cm above or below the cricoid level,
      respectively). Color Doppler ultrasound was used to study whether new valvular
      incompetence was present during Valsalva maneuvers after insertion of a central
      venous catheter, immediately after removal of the catheter, and, in a subset of
      patients, several months after catheter removal, when compared with baseline
      findings before cannulation of the IJV. RESULTS: Incompetence of the IJV valve
      was frequently induced both by proximal and distal cannulation and
      catheterization of the IJV. Its incidence was higher after proximal than after
      distal cannulation (76% vs. 41%; P < 0.01) and tended to be so after removal of
      the catheter (47% vs. 28%; P = 0.07). Valvular incompetence persisting
      immediately after removal of the catheter did not recover within 8-27 months in
      most cases. CONCLUSIONS: Cannulation and catheterization of the IJV may cause
      persistent incompetence of the IJV valve. Choosing a more distal site for venous
      cannulation may slightly lower the risk of causing valvular incompetence but does
      not reliably avoid it.

PMID- 10910477
TI  - Preliminary report on the association of apolipoprotein E polymorphisms, with
      postoperative peak serum creatinine concentrations in cardiac surgical patients.
AB  - BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of
      patients and is associated with major increases in morbidity, mortality, and
      cost. Genetic polymorphisms have been implicated as a factor in the progression
      of chronic renal disease, but a genetic basis for the development of acute renal
      impairment has not been investigated. The authors therefore tested the hypothesis
      that apolipoprotein E alleles are associated with different postoperative changes
      in serum creatinine after cardiac surgery. METHODS: The authors performed a
      prospective observational study with use of data from 564 coronary bypass
      surgical patients who were enrolled in an ongoing investigation of apolipoprotein
      E genotypes and organ dysfunction at a university hospital between 1989-1999.
      Renal function was assessed among apolipoprotein E genotype groups by comparisons
      of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative
      change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping
      (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase
      in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26;
      E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and
      epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative
      serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2).
      There was no difference in baseline creatinine among allele groups. CONCLUSIONS:
      Inheritance of the apolipoprotein epsilon4 allele is associated with reduced
      postoperative increase in serum creatinine after cardiac surgery, compared with
      the epsilon3 or epsilon2 allele. This is the first report of a possible genetic
      basis for acute renal impairment. These data may contribute to renal risk
      stratification for cardiac surgery and raise questions regarding apolipoprotein E
      and the pathophysiology of acute renal injury.

PMID- 10910478
TI  - Omission of nitrous oxide from a propofol-based anesthetic does not affect the
      recovery of women undergoing outpatient gynecologic surgery.
AB  - BACKGROUND: Although nitrous oxide (N2O) is used commonly during anesthesia,
      clinically relevant advantages-disadvantages of using this agent are not well
      established in the ambulatory setting. This study in women undergoing ambulatory
      gynecologic surgery compares outcomes in patients administered total intravenous
      anesthesia with propofol versus the propofol plus N2O. The primary outcome was
      the time to home readiness. Secondary outcomes included the incidence of
      postanesthetic adverse events. METHODS: Women presenting for elective ambulatory
      termination of pregnancy or gynecologic laparoscopy were induced with an
      intravenous sleep dose of propofol and fentanyl. After induction, subjects were
      randomly allocated to maintenance anesthesia with propofol alone or propofol plus
      65% N2O. Patients were assessed by a blinded observer in the postanesthetic care
      unit at 20-min intervals to determine home readiness. Postoperative pain and
      nausea were measured with visual analog scales. Postoperative analgesics and
      antiemetics were recorded. The incidence of adverse events occurring after
      hospital discharge was assessed by a telephone interview 24 h postoperatively.
      RESULTS: A total of 740 patients received propofol alone, and 750 patients
      received propofol plus N2O. Mean home readiness times were not significantly
      different between treatment groups. There were no significant differences between
      groups in pain scores, nausea scores, analgesia administration, or antiemetic
      administration before discharge. There were no significant differences in the
      frequency of adverse events for 24 h after discharge from hospital. CONCLUSIONS:
      Omission of N2O from a propofol-based anesthetic for ambulatory gynecologic
      surgery does not affect time to home readiness or the incidence of postoperative
      adverse events up to 24 h after discharge from hospital. (Key words: Awareness;
      outpatient surgery; total intravenous anesthesia.)

PMID- 10910479
TI  - Use of the intubating laryngeal mask airway: are muscle relaxants necessary?
AB  - BACKGROUND: The intubating laryngeal mask airway (ILMA) is designed to facilitate
      blind tracheal intubation. The effect of a muscle relaxant on the ability to
      perform tracheal intubation through the ILMA device has not been previously
      evaluated. This randomized, double-blind, placebo-controlled study was designed
      to evaluate rocuronium, 0.2 or 0.4 mg/kg administered intravenously, on the
      success rate and incidence of complications associated with ILMA-assisted
      tracheal intubation. METHODS: A total of 75 healthy patients were induced with
      propofol 2 mg/kg and fentanyl 1 microg/kg intravenously. After insertion of the
      ILMA device, patients were administered either saline, rocuronium 0.2 mg/kg, or
      rocuronium 0.4 mg/kg in a total volume of 5 ml. At 90 s after administration of
      the study drug, tracheal intubation was attempted using a disposable polyvinyl
      tube. If unsuccessful, a reusable silicone tube was tried. In addition to
      recording the time and number of attempts required to secure the airway, the
      incidence of complications during placement of the tracheal tube and removal of
      the ILMA were noted. RESULTS: Tracheal intubation was successful in 76-96% of the
      patients. The overall success rates and times required to secure the airway were
      similar in all three treatment groups. The high-dose rocuronium group experienced
      less patient movement (8 vs. 28 and 48%) and coughing (12 vs. 20 and 52%) than
      the low-dose rocuronium and saline groups, respectively. Use of rocuronium was
      also associated with a dose-related decrease in the requirement for supplemental
      bolus doses of propofol during intubation and removal of the ILMA device.
      CONCLUSIONS: Use of rocuronium did not significantly improve the success rate in
      performing tracheal intubation through the ILMA. However, it produced dose
      related decreases in coughing and movement after tracheal intubation and reduced
      difficulties associated with removal of the ILMA device.

PMID- 10910480
TI  - Preanesthetic train-of-four fade predicts the atracurium requirement of
      myasthenia gravis patients.
AB  - BACKGROUND: The most sensitive diagnostic criterion of myasthenia gravis is a
      decrement in the muscular response to repetitive stimulation. The authors
      hypothesized that myasthenia gravis patients who show a train-of-four ratio
      (T4/T1) < 0.9 in the preanesthetic period will have increased sensitivity to
      nondepolarizing neuromuscular blocking agents compared with myasthenia gravis
      patients with preanesthetic T4/T1 > or = 0.9. METHODS: After institutional review
      board approval was obtained, 20 electrophysiologically documented myasthenia
      gravis patients were studied. Current pyridostigmine therapy was continued until
      the morning of surgery. Before induction of anesthesia, neuromuscular
      transmission was recorded from the hypothenar muscles using electromyography with
      train-of-four stimulation of the ulnar nerve. According to the T4/T1 ratio,
      patients were assigned to the "normal" group (T4/T1 > or = 0.9) or the
      "decrement" group (T4/T1 < 0.9). After induction of intravenous anesthesia, the
      effective dose to achieve a 95% neuromuscular blockade (ED95) for atracurium was
      assessed with a cumulative bolus technique. Postoperatively, pyridostigmine was
      titrated to obtain a T4/T1 > 0.75 and to treat residual myasthenic symptoms.
      RESULTS: In 14 patients, preanesthetic T4/T1 was > or = 0.9 (normal), whereas 6
      patients presented with T4/T1 < 0.9 (decrement). Decrement patients had a lower
      ED95 of 0.07 +/- 0.03 mg/kg atracurium (mean +/- SD) compared with normal
      patients with an ED95 of 0.24 +/- 0.11 mg/kg atracurium (P = 0.002). All patients
      were extubated within 30 min after surgery. Postoperative pyridostigmine infusion
      did not differ significantly between groups. CONCLUSIONS: The requirement for
      atracurium is significantly reduced in myasthenia gravis patients with a T4/T1
      ratio < 0.9 before anesthesia. This study indicates that routine neuromuscular
      monitoring in myasthenia gravis patients should be extended into the preinduction
      period to identify patients who require less atracurium.

PMID- 10910481
TI  - beta-adrenergic desensitization after burn excision not affected by the use of
      epinephrine to limit blood loss.
AB  - BACKGROUND: Burn patients have impaired myocardial function and decreased beta
      adrenergic responsiveness. Further beta-adrenergic dysfunction from systemic
      absorption of topically administered epinephrine that is given to limit blood
      loss during burn excision could affect perioperative management. The authors
      evaluated the effect of topical epinephrine administration to patients during
      burn excision on the lymphocytic beta-adrenergic response. METHODS: Fifty-five
      patients (age, 2-18 yr) with 20-90% body surface area burns received a
      standardized anesthetic for a burn excision procedure. Lymphocyte samples were
      taken at baseline and 1 and 3 h after the initial use of epinephrine (n = 43) or
      thrombin (controls, n = 12). Plasma epinephrine levels were measured by high
      performance liquid chromatography. Lymphocyte beta-adrenergic responsiveness was
      assessed by measuring production of cyclic adenosine monophosphate (cAMP) after
      stimulation with isoproterenol, prostaglandin E1 (PGE1), and forskolin. beta
      adrenergic receptor binding assays using iodopindolol and CGP12177 yielded beta
      adrenergic receptor density. RESULTS: Epinephrine levels were elevated at 1 h (P
      < 0.01) and 3 h (P < 0.01) after epinephrine use but not in control patients.
      Production of cAMP in lymphocytes 1 h after epinephrine was greater in patients
      receiving epinephrine than in control patients on stimulation with isoproterenol
      (P < 0.05) and PGE1 (P < 0.05). Three hours after epinephrine administration,
      production of cAMP decreased when compared with baseline in both control patients
      and those receiving epinephrine after stimulation with isoproterenol (P < 0. 05),
      PGE1(P < 0.05), and forskolin (P < 0.05). Lymphocytic beta-adrenergic receptor
      content was not changed. CONCLUSIONS: Topical epinephrine to limit blood loss
      during burn excision resulted in significant systemic absorption and increased
      plasma epinephrine levels. Acute sensitization of the lymphocytic beta-adrenergic
      cascade was induced by the administration of epinephrine reflected by increased
      cAMP production after stimulation with isoproterenol and PGE1. The lymphocytic
      beta-adrenergic cascade exhibited homologous and heterologous desensitization 3 h
      after the use of epinephrine or thrombin, indicating that epinephrine
      administration was not a causative factor.

PMID- 10910482
TI  - Endotoxin desensitization of human mononuclear cells after cardiopulmonary
      bypass: role of humoral factors.
AB  - BACKGROUND: The ability of leukocytes to release proinflammatory cytokines on
      lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass
      (CPB). This study tested contribution and interaction of humoral factors in
      altered leukocyte responsiveness to lipopolysaccharide. METHODS: Whole blood and
      isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained
      after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were
      cultured in the absence or presence of lipopolysaccharide and assessed for
      release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and
      their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In
      addition, dose-response characteristics and interaction of IL-10 and
      norepinephrine as modulators of TNF-alpha release were studied. RESULTS:
      Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25
      pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th
      percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce
      proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0
      6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal
      of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P <
      0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of
      PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or
      norepinephrine in concentrations present in plasma after CPB led to a reduced
      lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response.
      Coadministration of norepinephrine and IL-10 had synergistic effects. Although
      pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma
      obtained at T2 largely restored the TNF-alpha response in vitro, their addition
      post-treatment failed to restore the monocytic TNF-alpha response. CONCLUSIONS:
      Plasma contains interacting factors that inhibit the release of TNF-alpha and
      increase the release of IL-10, presumably attenuating the inflammatory response
      to CPB. Although norepinephrine fails to induce a cytokine response in the
      absence of other stimuli, its administration seems to augment the
      antiinflammatory IL-10 response while attenuating the TNF-alpha response.

PMID- 10910483
TI  - Arterial to end-tidal carbon dioxide pressure difference during laparoscopic
      surgery in pregnancy.
AB  - BACKGROUND: There is controversy about whether capnography is adequate to monitor
      pulmonary ventilation to reduce the risk of significant respiratory acidosis in
      pregnant patients undergoing laparoscopic surgery. In this prospective study,
      changes in arterial to end-tidal carbon dioxide pressure difference (PaCO2-
      PetCO2), induced by carbon dioxide pneumoperitoneum, were determined in pregnant
      patients undergoing laparoscopic cholecystectomy. METHODS: Eight pregnant women
      underwent general anesthesia at 17-30 weeks of gestation. Carbon dioxide
      pnueumoperitoneum was initiated after obtaining arterial blood for gas analysis.
      Pulmonary ventilation was adjusted to maintain PetCO2 around 32 mmHg during the
      procedure. Arterial blood gas analysis was performed during insufflation, after
      the termination of insufflation, after extubation, and in the postoperative
      period. RESULTS: The mean +/- SD for PaCO2--PetCO2 was 2.4 +/- 1.5 before carbon
      dioxide pneumoperitoneum, 2.6 +/- 1.2 during, and 1.9 +/- 1.4 mmHg after
      termination of pneumoperitoneum. PaCO2 and pH during pneumoperitoneum were 35 +/-
      1.7 mmHg and 7.41 +/- 0.02, respectively. There were no significant differences
      in either mean PaCO2--PetCO2 or PaCO2 and pH during various phases of
      laparoscopy. CONCLUSIONS: Capnography is adequate to guide ventilation during
      laparoscopic surgery in pregnant patients. Respiratory acidosis did not occur
      when PetCO2 was maintained at 32 mmHg during carbon dioxide pneumoperitoneum.

PMID- 10910484
TI  - Perioperative considerations in a patient with orthostatic intolerance syndrome.

PMID- 10910485
TI  - Desflurane as a marker of limb-to-systemic leak during hyperthermic isolated limb
      perfusion.

PMID- 10910486
TI  - Assessment of length-dependent regulation of myocardial function in coronary
      surgery patients using transmitral flow velocity patterns.
AB  - BACKGROUND: In a subset of coronary surgery patients, a transient increase in
      cardiac load by leg elevation resulted in a decrease in maximal rate of pressure
      development (dP/dtmax) and a major increase in end-diastolic pressure (EDP). This
      impairment of left ventricular (LV) function appeared to be related to a
      deficient length-dependent regulation of myocardial function. The present study
      investigated whether analysis of transmitral flow patterns with transesophageal
      echocardiography constituted a noninvasive method to identify these patients.
      METHODS: High-fidelity LV pressure tracings and transmitral flow signals were
      obtained in 50 coronary surgery patients during an increase in cardiac load by
      leg elevation. Using linear regression analysis, changes in transmitral E-wave
      velocity and deceleration time (DT) were related to changes in dP/dtmax and EDP.
      RESULTS: Changes in dP/dtmax with leg elevation were closely related to
      corresponding changes in E-wave velocity (r = 0.81; P < 0. 001) and to changes in
      DT (r = 0.78; P < 0.001). Similarly, changes in EDP were related to changes in E
      wave velocity (r = 0.83; P < 0. 001) and to changes in DT (r = 0.84; P < 0.001).
      The decrease in dP/dtmax and the major increase in EDP in some patients was
      associated with an increase in E-wave velocity and a decrease in DT, indicating
      development of a restrictive LV filling pattern. CONCLUSIONS: Impairment of LV
      function with leg elevation was associated with the development of a restrictive
      transmitral filling pattern. Analysis of transmitral flow patterns by means of
      transesophageal echocardiography therefore allowed noninvasive identification of
      a subset of coronary surgery patients with impaired length-dependent regulation
      of LV function.

PMID- 10910487
TI  - The effects of increasing plasma concentrations of dexmedetomidine in humans.
AB  - BACKGROUND: This study determined the responses to increasing plasma
      concentrations of dexmedetomidine in humans. METHODS: Ten healthy men (20-27 yr)
      provided informed consent and were monitored (underwent electrocardiography,
      measured arterial, central venous [CVP] and pulmonary artery [PAP] pressures,
      cardiac output, oxygen saturation, end-tidal carbon dioxide [ETCO2], respiration,
      blood gas, and catecholamines). Hemodynamic measurements, blood sampling, and
      psychometric, cold pressor, and baroreflex tests were performed at rest and
      during sequential 40-min intravenous target infusions of dexmedetomidine (0.5,
      0.8, 1.2, 2.0, 3.2, 5.0, and 8.0 ng/ml; baroreflex testing only at 0.5 and 0.8
      ng/ml). RESULTS: The initial dose of dexmedetomidine decreased catecholamines 45
      76% and eliminated the norepinephrine increase that was seen during the cold
      pressor test. Catecholamine suppression persisted in subsequent infusions. The
      first two doses of dexmedetomidine increased sedation 38 and 65%, and lowered
      mean arterial pressure by 13%, but did not change central venous pressure or
      pulmonary artery pressure. Subsequent higher doses increased sedation, all
      pressures, and calculated vascular resistance, and resulted in significant
      decreases in heart rate, cardiac output, and stroke volume. Recall and
      recognition decreased at a dose of more than 0.7 ng/ml. The pain rating and mean
      arterial pressure increase to cold pressor test progressively diminished as the
      dexmedetomidine dose increased. The baroreflex heart rate slowing as a result of
      phenylephrine challenge was potentiated at both doses of dexmedetomidine.
      Respiratory variables were minimally changed during infusions, whereas acid-base
      was unchanged. CONCLUSIONS: Increasing concentrations of dexmedetomidine in
      humans resulted in progressive increases in sedation and analgesia, decreases in
      heart rate, cardiac output, and memory. A biphasic (low, then high) dose-response
      relation for mean arterial pressure, pulmonary arterial pressure, and vascular
      resistances, and an attenuation of the cold pressor response also were observed.

PMID- 10910488
TI  - Epidural infusion of ropivacaine for postoperative analgesia after major
      orthopedic surgery: pharmacokinetic evaluation.
AB  - BACKGROUND: Changing plasma protein concentrations may affect the protein binding
      and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors
      evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural
      infusion to provide postoperative analgesia. METHODS: Twenty-eight patients,
      scheduled for major orthopedic surgery during combined epidural and general
      anesthesia received a bolus dose of ropivacaine (50 or 75 mg), followed by
      constant-rate (10 ml/h) epidural infusion of ropivacaine 2 mg/ml (group 1) or 3
      mg/ml (group 2). Total and unbound plasma concentrations of ropivacaine and
      pipecoloxylidide and plasma concentrations of alpha1-acid glycoprotein were
      determined. In addition, the urinary excretion of ropivacaine and major
      metabolites was measured. RESULTS: Total plasma concentrations of ropivacaine
      increased steadily during the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l
      in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine
      concentrations reached average steady state levels of approximately 0.06 and 0.07
      mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/-
      0.4 and 0.4 +/- 0.2 mg/l (group 1) and 1.2 +/- 0.4 and 0.5 +/- 0.1 mg/l (group 2)
      after 72 h infusion. alpha1-Acid glycoprotein concentrations initially decreased,
      but thereafter increased steadily to approximately twice the baseline values.
      CONCLUSIONS: Postoperative increases in plasma alpha1-acid glycoprotein
      concentrations enhance the protein binding of ropivacaine and pipecoloxylidide,
      causing divergence of total and unbound plasma concentrations.

PMID- 10910489
TI  - Absence of bronchodilation during desflurane anesthesia: a comparison to
      sevoflurane and thiopental.
AB  - BACKGROUND: Bronchospasm is a potential complication in anyone undergoing general
      anesthesia. Because volatile anesthetics relax bronchial smooth muscle, the
      effects of two newer volatile anesthetics, desflurane and sevoflurane, on
      respiratory resistance were evaluated. The authors hypothesized that desflurane
      would have greater bronchodilating effects because of its ability to increase
      sympathetic nervous system activity. METHODS: Informed consent was obtained from
      patients undergoing elective surgery with general anesthesia. We recorded airway
      flow and pressure after thiopental induction and tracheal intubation (baseline)
      and for 10 min after beginning volatile anesthesia ( approximately 1 minimum
      alveolar concentration inspired). Respiratory system resistance was determined
      using the isovolume technique. RESULTS: Fifty subjects were randomized to receive
      sevoflurane (n = 20), desflurane (n = 20), or thiopental infusion (n = 10, 0.25
      mg. kg-1. h-1). There were no differences between groups for age, height, weight,
      smoking history, and American Society of Anesthesiologists physical class. On
      average, sevoflurane reduced respiratory resistance 15% below baseline, whereas
      both desflurane (+5%) and thiopental (+10%) did not decrease respiratory
      resistance. The respiratory resistance changes did not differ in patients with
      and without a history of smoking during sevoflurane or thiopental. In contrast,
      administration of desflurane to smokers resulted in the greatest increase in
      respiratory resistance. CONCLUSIONS: Sevoflurane causes moderate bronchodilation
      that is not observed with desflurane or sodium thiopental. The
      bronchoconstriction produced by desflurane was primarily noted in patients who
      currently smoked. (Key words: Bronchospasm; respiratory resistance; volatile
      anesthetics.)

PMID- 10910490
TI  - Acute opioid tolerance: intraoperative remifentanil increases postoperative pain
      and morphine requirement.
AB  - BACKGROUND: Rapid development of acute opioid tolerance is well established in
      animals and is more likely to occur with large doses of short-acting drugs. The
      authors therefore tested the hypothesis that intraoperative remifentanil
      administration results in acute opioid tolerance that is manifested by increased
      postoperative pain and opioid requirement. METHODS: Fifty adult patients
      undergoing major abdominal surgery were randomly assigned to two anesthetic
      regimens: (1) desflurane was kept constant at 0.5 minimum alveolar concentrations
      and a remifentanil infusion was titrated to autonomic responses (remifentanil
      group); or (2) remifentanil at 0.1 microg. kg-1. min-1 and desflurane titrated to
      autonomic responses (desflurane group). All patients were given a bolus of 0.15
      mg/kg morphine 40 min before the end of surgery. Morphine was initially titrated
      to need by postanesthesia care nurses blinded to group assignment. Subsequently,
      patients-who were also blinded to group assignment-controlled their own morphine
      administration. Pain scores and morphine consumption were recorded for 24
      postoperative h. RESULTS: The mean remifentanil infusion rate was 0.3 +/- 0.2
      microg. kg-1. min-1 in the remifentanil group, which was significantly greater
      than in the desflurane group. Intraoperative hemodynamic responses were similar
      in each group. Postoperative pain scores were significantly greater in the
      remifentanil group. These patients required morphine significantly earlier than
      those in the desflurane group and needed nearly twice as much morphine in the
      first 24 postoperative h: 59 mg (25-75% interquartile range, 43-71) versus 32 mg
      (25-75% interquartile range, 19-59; P < 0.01). CONCLUSIONS: Relatively large-dose
      intraoperative remifentanil increased postoperative pain and morphine
      consumption. These data suggest that remifentanil causes acute opioid tolerance
      and hyperalgesia.

PMID- 10910491
TI  - Subarachnoid meperidine (Pethidine) causes significant nausea and vomiting during
      labor. The Duke Women's Anesthesia Research Group.
AB  - BACKGROUND: The combined spinal-epidural (CSE) technique using bupivicaine
      fentanyl has become an established method of pain control during parturition. One
      limitation is the relatively short duration of effective analgesia produced by
      bupivicaine-fentanyl. In contrast, subarachnoid meperidine has been shown to
      provide a long duration of anesthesia in nonobstetric patients. Therefore, the
      authors tested the hypothesis that subarachnoid meperidine produces a significant
      increase in the duration of analgesia compared with bupivicaine-fentanyl.
      METHODS: Based on a power analysis of preliminary data, the authors intended to
      recruit 90 patients for the study, randomized to three groups: 2.5 mg bupivicaine
      25 microg fentanyl, 15 mg meperidine, or 25 mg meperidine. However, after
      enrolling 34 patients, the study was discontinued because of a significant
      increase in nausea or vomiting in the study patients. RESULTS: Nausea or vomiting
      was substantially increased in both meperidine groups compared with the
      bupivicaine-fentanyl group: 16 with nausea or vomiting in the meperidine groups
      (n = 21), compared with 1 in the bupivicaine-fentanyl group (n = 11), P = 0.0011.
      The mean duration of analgesia provided by 25 mg meperidine was 126 +/- 51 min,
      compared with 98 +/- 29 min for bupivicaine-fentanyl and 90 +/- 67 min for 15 mg
      meperidine. These data were not significant (P = 0.27). CONCLUSIONS: Although
      intrathecal meperidine could potentially prolong subarachnoid analgesia during
      labor, its use was associated with a significant incidence of nausea or vomiting.
      These data do not support the use of subarachnoid meperidine in doses of 15 or 25
      mg for labor analgesia.

PMID- 10910492
TI  - Effects of intravenous Zaprinast and inhaled nitric oxide on pulmonary
      hemodynamics and gas exchange in an ovine model of acute respiratory distress
      syndrome.
AB  - BACKGROUND: Inhaled nitric oxide (No) selectively dilates the pulmonary
      vasculature and improves gas exchange in acute respiratory distress syndrome.
      Because of the very short half-life of NO, inhaled NO is administered
      continuously. Intravenous Zaprinast (2-o-propoxyphenyl-8-azapurin-6-one), a
      cyclic guanosine monophosphate phosphodiesterase inhibitor, increases the
      efficacy and prolongs the duration of action of inhaled NO in models of acute
      pulmonary hypertension. Its efficacy in lung injury models is uncertain. The
      authors hypothesized that the use of intravenous Zaprinast would have similar
      beneficial effects when used in combination with inhaled NO to improve
      oxygenation and dilate the pulmonary vasculature in a diffuse model of acute lung
      injury. METHODS: The authors studied two groups of sheep with lung injury
      produced by saline lavage. In the first group, 0, 5, 10, and 20 ppm of inhaled NO
      were administered in a random order before and after an intravenous Zaprinast
      infusion (2 mg/kg bolus followed by 0.1 mg. kg-1. min-1). In the second group,
      inhaled NO was administered at the same concentrations before and after an
      intravenous infusion of Zaprinast solvent (0.05 m NaOH). RESULTS: After lavage,
      inhaled NO decreased pulmonary arterial pressure and resistance with no systemic
      hemodynamic effects, increased arterial oxygen partial pressure, and decreased
      venous admixture (all P < 0.05). The intravenous administration of Zaprinast
      alone decreased pulmonary artery pressure but worsened gas exchange (P < 0.05).
      Zaprinast infusion abolished the beneficial ability of inhaled NO to improve
      pulmonary gas exchange and reduce pulmonary artery pressure (P < 0. 05 vs.
      control). CONCLUSIONS: This study suggests that nonselective vasodilation induced
      by intravenously administered Zaprinast at the dose used in our study not only
      worsens gas exchange, but also abolishes the beneficial effects of inhaled NO.

PMID- 10910493
TI  - Anesthetic effects on cerebral metabolic rate predict histologic outcome from
      near-complete forebrain ischemia in the rat.
AB  - BACKGROUND: Although reduction of cerebral metabolic rate is thought to
      contribute to anesthetic neuroprotection, histologic evidence to support this
      concept has not been provided. In this study, histologic outcome was evaluated in
      rats subjected to different durations of severe forebrain ischemia while
      anesthetized with volatile anesthetics that have substantially different effects
      on cerebral metabolic rate. METHODS: Normothermic rats that underwent fasting
      were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60%
      nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use
      of a combination of bilateral carotid occlusion and controlled hypotension. Rats
      in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas
      the halothane group received 6.5 min ischemia. Histologic damage was assessed 4
      days later. RESULTS: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent
      of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus
      halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead
      neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no
      difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0.
      935). A similar pattern was observed in hippocampal CA4 and the neocortex.
      Striatal damage was not affected by anesthetic or ischemic duration. CONCLUSIONS:
      At 6.5 min ischemia, isoflurane provided improved outcome versus halothane.
      Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to
      onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate
      by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of
      ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome
      became similar to that in halothane-N2O-anesthetized rats. These results provide
      evidence that cerebral metabolic rate reduction has an advantageous effect on
      outcome from severe brain ischemia, but also suggest that such benefit is likely
      to be small.

PMID- 10910494
TI  - Propofol selectively attenuates endothelium-dependent pulmonary vasodilation in
      chronically instrumented dogs.
AB  - BACKGROUND: The objective was to investigate the effects of propofol anesthesia
      on the pulmonary vascular response to endothelium-dependent and -independent
      vasodilators, compared with the responses measured in the conscious state.
      METHODS: Twenty-six conditioned, male, mongrel dogs were instrumented long-term
      to measure the left pulmonary vascular pressure-flow relation. Pressure-flow
      plots were measured on separate days in conscious and propofol-anesthetized (5.0
      mg/kg plus 0.5 mg. kg-1. min-1 intravenously) dogs at baseline, after
      preconstriction with the thromboxane mimetic U46619, and during the cumulative
      intravenous administration of endothelium-dependent (acetylcholine and
      bradykinin) and -independent (proline-nitric oxide) vasodilators. RESULTS:
      Propofol had no effect on the baseline pressure-flow relation compared with the
      conscious state. A lower (P < 0.05) dose of U46619 was necessary to achieve the
      same degree of preconstriction during propofol anesthesia. The pulmonary
      vasodilator responses to bradykinin and proline-nitric oxide were similar in the
      conscious and propofol-anesthetized states. In contrast, the pulmonary
      vasodilator response to acetylcholine was markedly attenuated (P < 0.01) during
      propofol anesthesia. The intralipid vehicle for propofol had no effect on the
      acetylcholine dose-response relation. CONCLUSION: These results suggest that
      propofol causes a specific defect in the signal transduction pathway for
      acetylcholine-induced pulmonary vasodilation. This defect involves the
      endothelial and not the vascular smooth muscle component of the response.

PMID- 10910495
TI  - Propofol attenuates acetylcholine-induced pulmonary vasorelaxation: role of
      nitric oxide and endothelium-derived hyperpolarizing factors.
AB  - BACKGROUND: The mechanism by which propofol selectively attenuates the pulmonary
      vasodilator response to acetylcholine is unknown. The goals of this study were to
      identify the contributions of endogenous endothelial mediators (nitric oxide
      [NO], prostacyclin, and endothelium-derived hyperpolarizing factors [EDHFs]) to
      acetylcholine-induced pulmonary vasorelaxation, and to delineate the extent to
      which propofol attenuates responses to these endothelium-derived relaxing
      factors. METHODS: Canine pulmonary arterial rings were suspended for isometric
      tension recording. The effects of propofol on the vasorelaxation responses to
      acetylcholine, bradykinin, and the guanylyl cyclase activator, SIN-1, were
      assessed in phenylephrine-precontracted rings. The contributions of NO,
      prostacyclin, and EDHFs to acetylcholine-induced vasorelaxation were assessed in
      control and propofol-treated rings by pretreating the rings with a NO synthase
      inhibitor (l-NAME), a cyclooxygenase inhibitor (indomethacin), and a cytochrome
      P450 inhibitor (clotrimazole or SKF 525A) alone and in combination. RESULTS:
      Propofol caused a dose-dependent rightward shift in the acetylcholine dose
      response relation, whereas it had no effect on the pulmonary vasorelaxant
      responses to bradykinin or SIN-1. Cyclooxygenase inhibition only attenuated
      acetylcholine-induced relaxation at high concentrations of the agonist. NO
      synthase inhibition and cytochrome P450 inhibition each attenuated the response
      to acetylcholine, and combined inhibition abolished the response. Propofol
      further attenuated acetylcholine-induced relaxation after NO synthase inhibition
      and after cytochrome P450 inhibition. CONCLUSION: These results suggest that
      acetylcholine-induced pulmonary vasorelaxation is mediated by two components: NO
      and a cytochrome P450 metabolite likely to be an EDHF. Propofol selectively
      attenuates acetylcholine-induced relaxation by inhibiting both of these
      endothelium-derived mediators.

PMID- 10910496
TI  - Absence of stereospecific effects of bupivacaine isomers on heart mitochondrial
      bioenergetics.
AB  - BACKGROUND: Highly lipophilic local anesthetics interfere with mitochondrial
      energy metabolism. These metabolic effects could, in part, explain some toxic
      effects of local anesthetics, such as bupivacaine-induced myocardial depression.
      The purpose of this study was to compare the optically pure isomers of
      bupivacaine on heart mitochondrial bioenergetics. METHODS: Both bupivacaine
      enantiomers were tested on rat heart isolated mitochondria. Oxygen consumption,
      adenosine triphosphate synthesis, and enzymatic activities of the four complexes
      of the respiratory chain were measured. RESULTS: No significant differences were
      found between R(+)- and S(-)-bupivacaine on mitochondrial oxidative
      phosphorylation with a similar dose-dependent decrease in adenosine triphosphate
      synthesis. Complex I (nicotinamide adenine dinucleotide ubiquinone reductase) was
      the enzymatic complex of the respiratory chain most sensitive to the bupivacaine
      isomers. Half-inhibitory concentrations for R(+)- and S(-)-bupivacaine were not
      statistically different (3.3 +/- 0.4 mm and 2.8 +/- 0.6 mm, respectively).
      CONCLUSIONS: No stereospecific effects of bupivacaine enantiomers were shown in
      the inhibition of complex I activity and uncoupling of oxidative phosphorylation.
      This can be correlated with the lack of stereospecific effects of bupivacaine on
      myocardial depression. The lipid solubility of local anesthetics appears to be
      the principal physicochemical factor affecting the potency of these tertiary
      amines on mitochondrial bioenergetics.

PMID- 10910497
TI  - Effects of propofol on hippocampal synaptic transmission in behaving rats.
AB  - BACKGROUND: The action of propofol has been studied in vitro and in vivo, but the
      effects of intravenously administered propofol on synaptic transmission in freely
      behaving rats have not been studied before. METHODS: Rats were implanted with
      recording electrodes in the dentate gyrus and with stimulation electrodes in the
      medial perforant path (MPP). Paired pulses at different interpulse intervals
      (IPIs) were delivered to the MPP, and average evoked potentials were recorded in
      the dentate gyrus before and after a bolus of propofol (10 or 20 mg/kg
      administered intravenously) or control vehicle was injected via femoral vein
      cannula. Because of the layered structure of the hippocampus, population
      excitatory postsynaptic potentials and population spikes could be distinguished
      and analyzed. RESULTS: Propofol has no significant effect on the population
      excitatory postsynaptic potentials or population spike evoked by a single MPP
      stimulus pulse. However, paired-pulse inhibition of the dentate population spikes
      was increased at IPI of 20 and 30 ms. Paired-pulse inhibition of the population
      spike was most prominent when tail pinch response was lost (deep and moderate
      anesthesia), but it persisted during light anesthesia. At 200 ms IPI, paired
      pulse facilitation of population spikes was observed during moderate anesthesia
      in most rats. CONCLUSIONS: In freely behaving rats, intravenous propofol enhanced
      paired-pulse inhibition at < 50 ms IPI, likely by enhancing gamma-aminobutyric
      acid A receptor-mediated inhibition. Propofol also increased paired-pulse
      facilitation at 200 ms IPI through an unknown mechanism, which may contribute to
      the neuroexcitatory effect of propofol.

PMID- 10910498
TI  - Effects of radolmidine, a novel alpha2 -adrenergic agonist compared with
      dexmedetomidine in different pain models in the rat.
AB  - BACKGROUND: Intrathecally administered alpha2-adrenoceptor agonists produce
      effective antinociception, but sedation is an important adverse effect.
      Radolmidine is a novel alpha2-adrenoceptor agonist with a different
      pharmacokinetic profile compared with the well-researched dexmedetomidine. This
      study determined the antinociceptive and sedative effects of radolmidine in
      different models of acute and chronic pain. Dexmedetomidine and saline served as
      controls. METHODS: Male Sprague-Dawley rats were studied in acute pain (tail
      flick), carrageenan inflammation, and the spinal nerve ligation model of
      neuropathic pain. Mechanical allodynia was assessed with von Frey filaments, cold
      allodynia with the acetone test, and thermal hyperalgesia with the paw flick
      test. Locomotor activity-vigilance was assessed in a dark field. Dexmedetomidine
      and radolmidine were administered intrathecally in doses of 0.25 microg, 2.5
      microg, 5 microg, and 10 microg. RESULTS: In the tail flick test, radolmidine
      showed a dose-dependent antinociceptive effect, being equipotent compared with
      dexmedetomidine. In carrageenan inflammation, intrathecal doses of 2.5 microg or
      5 microg of dexmedetomidine/radolmidine produced significant antinociception
      compared with saline (P < 0.01). The two drugs were equianalgesic. In the
      neuropathic pain model, an intrathecal dose of 5 microg dexmedetomidine
      radolmidine had a significant antiallodynic effect compared with saline (P <
      0.01). The two drugs were equipotent. Intrathecal administration of both
      dexmedetomidine and radolmidine dose dependently decreased spontaneous locomotor
      acitivity-vigilance, but this effect was significantly smaller after intrathecal
      administration of radolmidine than after intrathecal dexmedetomidine.
      CONCLUSIONS: Radolmidine and dexmedetomidine had equipotent antinociceptive
      effects in all tests studied. However, radolmidine caused significantly less
      sedation than dexmedetomidine, probably because of a different pharmacokinetic
      profile.

PMID- 10910499
TI  - Propofol stimulates ciliary motility via the nitric oxide-cyclic GMP pathway in
      cultured rat tracheal epithelial cells.
AB  - BACKGROUND: Airway ciliary motility is impaired by inhaled anesthetics. Recent
      reports show that nitric oxide (NO) induces upregulation in ciliary beat
      frequency (CBF), and others report that propofol, an intravenous anesthetic,
      stimulates NO release; this raises the possibility that propofol increases CBF by
      stimulating the NO-cyclic guanosine monophosphate (cGMP) signal pathway. In this
      study, the authors investigated the effects of propofol on CBF and its relation
      with the NO-cGMP pathway using the pharmacologic blockers NG-monomethyl-l
      arginine (l-NMMA), an NO synthase inhibitor; 1H-[1,2,4]oxidazole[4,3-a]quinoxalin
      1-one (ODQ), a soluble guanylyl cyclase inhibitor; and KT5823, a cGMP-dependent
      protein kinase inhibitor, in cultured rat tracheal epithelial cells. METHODS: Rat
      tracheal tissues were explanted and cultured for 3-5 days. Images of ciliated
      cells were videotaped using a phase-contrast microscope. Baseline CBF and CBF 25
      min after exposure to propofol or blocker were measured using video analysis.
      RESULTS: Vehicle (0.1% dimethyl sulfoxide; n = 11) increased CBF by 0.2 +/- 1.7%
      (mean +/- SD) from baseline. Propofol stimulated CBF significantly (P < 0.01) and
      dose dependently (1 microM, 2.0 +/- 1. 9%, n = 6; 10 microM, 8.2 +/- 6.7%, n = 9;
      100 microM, 14.0 +/- 4.7%, n = 10). Intralipid (0.05%), the clinical vehicle of
      propofol, did not affect CBF (-0.2 +/- 2.2%; n = 5). The enhancement of CBF with
      use of 100 microm propofol was abolished (P < 0.01) by coadministration of 10
      mmicroM l-NMMA (2.4 +/- 3.6%; n = 5), 100 microM ODQ (-0.3 +/- 2.2%; n = 6) or 30
      microM KT5823 (-0.1 +/- 4. 1%; n = 8). l-NMMA, ODQ, or KT5823 alone did not
      change CBF. CONCLUSIONS: These results show that propofol stimulates CBF viathe
      NO-cGMP pathway in rat tracheal epithelial cells, suggesting a possible advantage
      of propofol in decreasing respiratory risk.

PMID- 10910500
TI  - Effect of pretreatment with intrathecal excitatory amino acid receptor
      antagonists on the development of pain behavior caused by plantar incision.
AB  - BACKGROUND: Drugs that block spinal excitatory amino acid receptor activation may
      prevent pain after surgery. The authors previously studied the effect of
      excitatory amino acid receptor antagonists after incision. In the present study,
      we examined the role of N-methyl-d-aspartate (NMDA), non-NMDA, and metabotropic
      glutamate receptors (mGluRs) on the development of pain behavior after plantar
      incision. METHODS: Rats with lumbar intrathecal catheters were anesthetized with
      halothane. Fifteen minutes before an incision was made, drug [40 nmol MK-801; 20
      nmol NBQX; or 200 nmol (+)-MCPG] or vehicle was injected intrathecally followed
      by an infusion of the same drug for 75 min. Withdrawal thresholds to calibrated
      von Frey filaments applied adjacent to the wound and response frequencies to a
      blunt mechanical stimulus applied directly to the wound were measured before
      incision and 1, 2, 4, and 6 h after incision and then once daily for 6 days.
      RESULTS: Preincision treatments with antagonists against the NMDA (MK-801) and
      group I and II metabotropic receptors [(+)-MCPG] did not inhibit the development
      of mechanical hyperalgesia caused by incision. Preincision treatment with the non
      NMDA receptor antagonist NBQX increased withdrawal thresholds at 1 and 2 h and on
      postoperative day 1 compared with the vehicle group; response frequencies were
      reduced 1 and 2 h after incision and on postoperative day 2 (P < 0.05). In an
      additional group, postincision treatment with NBQX was similar to preincision
      treatment. CONCLUSION: Spinal NMDA and mGluR antagonists may not be useful for
      preventing postsurgical pain. Spinal non-NMDA receptor antagonists reduced pain
      behaviors, but a preventive effect using preincision treatment was not apparent.

PMID- 10910501
TI  - Local anesthetic inhibition of m1 muscarinic acetylcholine signaling.
AB  - BACKGROUND: Local anesthetics inhibit lipid mediator signaling
      (lysophosphatidate, thromboxane) by acting on intracellular domains of the
      receptor or on the G protein. On receptors for polar agonists, the ligand-binding
      pocket could form an additional site of interaction, possibly resulting in
      superadditive inhibition. The authors therefore investigated the effects of local
      anesthetics on m1 muscarinic receptor functioning. METHODS: The authors expressed
      receptors in isolation using Xenopus oocytes. Using a two-electrode voltage
      clamp, the authors measured the effects of lidocaine, QX314 (permanently
      charged), and benzocaine (permanently uncharged) on Ca2+-activated Cl- currents
      elicited by methylcholine. The authors also characterized the interaction of
      lidocaine with [3H] quinuclydinyl benzylate ([3H]QNB) binding to m1 receptors.
      RESULTS: Lidocaine inhibited muscarinic signaling with a half-maximal inhibitory
      concentration (IC50 18 nm) 140-fold less than that of extracellularly
      administered QX314 (IC50 2.4 microm). Intracellularly injected QX314 (IC50 0.96
      mm) and extracellularly applied benzocaine (IC50 1.2 mm) inhibited at high
      concentrations only. Inhibition of muscarinic signaling by extracellularly
      applied QX314 and lidocaine was the result of noncompetitive antagonism.
      Intracellularly injected QX314 and benzocaine inhibited muscarinic and
      lysophosphatidate signaling at similar concentrations, suggesting an action on
      the common G-protein pathway. Combined administration of intracellularly injected
      (IC50 19 microm) and extracellularly applied QX314 (IC50 49 nm) exerted
      superadditive inhibition. Lidocaine did not displace specific [3H]QNB binding to
      m1 receptors. CONCLUSIONS: m1 Muscarinic signaling is inhibited by clinically
      relevant concentrations of lidocaine and by extracellularly administered QX314,
      suggesting that the major site of action is a extracellular domain of the
      muscarinic receptor. An additional less potent but superadditive inhibitory
      effect on the G-protein is suggested.

PMID- 10910503
TI  - Analgesic mechanisms of ketamine in the presence and absence of peripheral
      inflammation.
AB  - BACKGROUND: The studies on the mechanisms of ketamine antinociception have led to
      conflicting results. In this study, the authors investigated the contribution of
      supraspinal monoaminergic descending inhibitory system to ketamine analgesia for
      acute nociception and inflammation-induced hyperalgesia. METHODS: Male Sprague
      Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were
      measured to assess the thermal nociceptive threshold. The analgesic effects of
      intrathecal or intraperitoneal ketamine were examined in the rats that received
      unilateral intraplantar carrageenan and in those that were untreated. In
      addition, it was examined whether pretreatment with intrathecal yohimbine or
      methysergide inhibited the analgesic effects of ketamine. Using an intrathecal
      microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in
      lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both
      saline- and carrageenan-treated rats. RESULTS: In the untreated rats,
      intraperitoneal but not intrathecal ketamine produced antinociceptive effects in
      a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide
      inhibited these antinociceptive effects. Intraplantar carrageenan significantly
      reduced paw withdrawal latencies on the injected paw but not on the contralateral
      paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw
      withdrawal latencies on the injected side in a dose-dependent manner without any
      effects on the contralateral side. Neither yohimbine nor methysergide inhibited
      these antihyperalgesic effects. In analyses of monoamines, the magnitude of
      increase in monoamines after intraperitoneal ketamine was significantly smaller
      in the carrageenan-treated rats than in the saline-treated rats. CONCLUSION:
      These results demonstrated that ketamine produced antinociceptive effects through
      an activation of the monoaminergic descending inhibitory system, whereas, in a
      unilateral peripheral inflammation-induced hyperalgesic state, the monoaminergic
      system did not contribute to the antihyperalgesic effects of ketamine. The
      mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are
      different.

PMID- 10910502
TI  - Cholinesterase inhibition by potato glycoalkaloids slows mivacurium metabolism.
AB  - BACKGROUND: The duration of action for many pharmaceutical agents is dependent on
      their breakdown by endogenous hydrolytic enzymes. Dietary factors that interact
      with these enzyme systems may alter drug efficacy and time course.
      Cholinesterases such as acetylcholinesterase (AChE) and butyrylcholinesterase
      (BuChE) hydrolyze and inactivate several anesthetic drugs, including cocaine,
      heroin, esmolol, local ester anesthetics, and neuromuscular blocking drugs.
      Natural glycoalkaloid toxins produced by plants of the family Solanaceae, which
      includes potatoes and tomatoes, inhibit both AChE and BuChE. Here the authors
      assess the extent to which two solanaceous glycoalkaloids (SGAs), alpha-solanine
      and alpha-chaconine, can alter the effects of neuromuscular blocking drugs and
      cholinesterase inhibitors in vivo and in vitro. METHODS: Inhibition of purified
      human AChE and BuChE by SGAs, neuromuscular blocking drugs, and cholinesterase
      inhibitors was assessed by an in vitro colorimetric cholinesterase assay. In vivo
      experiments were carried out using anesthetized rabbits to test whether SGAs
      affect recovery from mivacurium-induced paralysis. RESULTS: SGAs inhibited human
      BuChE at concentrations similar to those found in serum of individuals who have
      eaten a standard serving of potatoes. Coapplication of SGAs (30-100 nm) with
      neuromuscular blocking drugs and cholinesterase inhibitors produced additive
      cholinesterase inhibition. SGA administration to anesthetized rabbits inhibited
      serum cholinesterase activity and mivacurium hydrolysis. In addition, SGA
      prolonged the time needed for recovery from mivacurium-induced paralysis (149 +/-
      12% of control; n = 12). CONCLUSIONS: These findings support the hypothesis that
      inhibition of endogenous enzyme systems by dietary factors can influence
      anesthetic drug metabolism and duration of action. Diet may contribute to the
      wide variation in recovery time from neuromuscular blockade seen in normal,
      healthy individuals.

PMID- 10910504
TI  - Process analysis in outpatient knee surgery: effects of regional and general
      anesthesia on anesthesia-controlled time.
AB  - BACKGROUND: The performance of anesthetic procedures before operating room entry
      (e.g., with either general or regional anesthesia [RA] induction rooms) should
      decrease anesthesia-controlled time in the operating room. The authors
      retrospectively studied the associations between anesthesia techniques and
      anesthesia-controlled time, evaluating one surgeon performing a single procedure
      over a 3-yr period. The authors hypothesized that, using the anesthesia care team
      model, RA would be associated with reduced anesthesia-controlled time compared
      with general anesthesia (GA) alone or combined general-regional anesthesia (GA
      RA). METHODS: The authors queried an institutional database for 369 consecutive
      patients undergoing the same procedure (anterior cruciate ligament
      reconstruction) performed by one surgeon over a 3-yr period (July 1995 through
      June 1998). Throughout the period of study, anesthesia staffing consisted of an
      attending anesthesiologist medically directing two nurse anesthetists in two
      operating rooms. Anesthesia-controlled time values were compared based on
      anesthesia techniques (GA, RA, or GA-RA) using one-way analysis of variance,
      general linear modeling using time-series and seasonal adjustments, and chi
      square tests when appropriate. P < 0. 05 was considered significant. RESULTS: RA
      was associated with the lowest anesthesia-controlled time (11.4 +/- 1.3 min, mean
      +/- 2 SEM). GA-RA (15.7 +/- 1.0 min) was associated with lower anesthesia
      controlled time than GA used alone (20.3 +/- 1.2 min). CONCLUSIONS: When compared
      with GA without an induction room for outpatients undergoing anterior cruciate
      ligament reconstruction, RA with an induction room was associated with the lowest
      anesthesia- controlled time. Managers must weigh the costs and time required for
      anesthesiologists and additional personnel to place nerve blocks or induce GA
      preoperatively in such a staffing model.

PMID- 10910505
TI  - Gender differences in opioid-mediated analgesia: animal and human studies.

PMID- 10910506
TI  - Anesthesiologists and perioperative communication.

PMID- 10910507
TI  - Rovenstine lecture: patient values, Hippocrates, science, and technology: what we
      (physicians) can do versus what we should do for the patient.

PMID- 10910508
TI  - An additional dimension to the efficacy of epidural steroids.

PMID- 10910509
TI  - Need for precise diagnosis prior to epidural steroids.

PMID- 10910510
TI  - Intraabdominal bleeding masked by hemodilution after hysteroscopy.

PMID- 10910511
TI  - Right atrial membrane interfering with insertion of pulmonary artery catheter.

PMID- 10910512
TI  - Anaphylaxis during insertion of a ventriculoperitoneal shunt.

PMID- 10910513
TI  - Paravertebral lumbar sympathetic block for labor analgesia.

PMID- 10910514
TI  - Ambulatory continuous perineural infusion: are we ready?

PMID- 10910515
TI  - Nonopioid analgesia improves outcomes.

PMID- 10910516
TI  - Use of supplemental oxygen during surgery is not risk free.

PMID- 10910517
TI  - Supplemental oxygen for the prevention of nausea and vomiting.

PMID- 10910518
TI  - Gastropathy and NSAIDs.

PMID- 10910519
TI  - Electric pumps and hyperbaric treatment.

PMID- 10910520
TI  - WuScope versus conventional laryngoscope in cervical spine immobilization.

PMID- 10910521
TI  - Cardiac arrest in multiple visceral organ transplantation: successful treatment
      with continuous venovenous hemodiafiltration.

PMID- 10910522
TI  - Use of the univent bronchial-blocker tube for unanticipated difficult
      endotracheal intubation.

PMID- 10910524
TI  - Positive breath alcohol readings following "generic" propofol administration.

PMID- 10910523
TI  - Acute hypoglycemia following combined spinal-epidural anesthesia (CSE) in a
      parturient with diabetes mellitus.

PMID- 10910525
TI  - Caudal anesthesia with ropivacaine in an awake 1,090-g baby.

PMID- 10910526
TI  - Retinopathy in patients with type 1 diabetes 4 years after intensive therapy.

PMID- 10910527
TI  - Biracial Japanese American identity: an evolving process.
AB  - This qualitative study explored the complexity of biracial identity development
      in Japanese Americans. It is based on the constant comparable method of analysis,
      or grounded theory. The study focused on how Japanese Americans perceived
      themselves in relation to other individuals, groups, and their environment. The
      data consisted of 15 extensive semistructured interviews with 8 men and 7 women
      (ages 20 to 40 years), each with 1 Japanese parent and 1 non-Asian parent.
      Findings relate to participants' initiating explorations of identity and
      perseverance in pursuing a biracial identity, which depended on the degree of
      support or negative experience within their social networks. Participants
      explored identity options attempting to develop their own meaning of identity, to
      develop a confident sense of themselves, and to secure a positive ethnic
      identity. Identity development among participants varied. It was a long-term
      process involving changes in the individual-environment relationship, which
      differed in the way individual participants influenced or selected from
      environmental opportunities, even creating or recreating some aspects. Within a
      given setting, as youths, the potential for social experiences were relatively
      fixed and changed only gradually. As adults, there were opportunities for
      participants to select their own social and geographic settings, providing
      opportunity for change. In their new environments, participants were exposed to
      new contacts and role models, acquired new behavioral repertoire, and underwent
      role transitions. Depending on this, new and different aspects of biracial
      identity developed. Participants indicated it was an emotional and conflictual
      process to positive assertion of identity. Before reaching this, all of the
      participants experienced periods of confusion. Most asserted biracial identity
      gradually, through a process of racial identity development consisting of the
      individual's changing or maintaining certain reference group perspectives,
      identifications, and allegiances as they passed through a series of life
      experiences. Instead of staying marginalized, they integrated both cultures,
      recognizing positive values of both, thus developing an integrated identity.
      Although the participants' experiences and perceptions were varied, the
      overarching themes of self-evaluation, confusion of categorization, belonging,
      infusion/exploration, situational use of identity, and resolution/acceptance/self
      verification were presented. On the basis of the research, a model of ethnic
      identity for biracial individuals is proposed.

PMID- 10910528
TI  - Acculturative stress, depression, and suicidal ideation in Mexican immigrants.
AB  - This study examined the relationship among acculturative stress, depression, and
      suicidal ideation in a sample of Mexican immigrants. Also examined were variables
      that predict depression and suicidal ideation. Multiple regression analyses
      revealed that acculturative stress significantly predicted depression and
      suicidal ideation and that family support, social support, religiosity, agreement
      with the decision to migrate, and expectations for the future were significant
      predictors of depression and suicidal ideation. The overall findings suggest that
      adult Mexican immigrants who experience elevated levels of acculturative stress
      may be at risk for experiencing critical levels of depression and suicidal
      ideation. The findings highlight the importance of using culturally relevant
      clinical methods when assessing and treating the depressed and potentially
      suicidal acculturating individual.

PMID- 10910529
TI  - The influence of self-efficacy on alcohol use among American Indians.
AB  - The influence of self-efficacy (general and substance use) on alcohol use among
      114 American Indian and Native Alaskan adults was examined. Analysis of variance
      was performed to assess differences between alcohol use groups (nonuse, low use,
      and medium-high use). Low general self-efficacy (GSE) was associated with higher
      alcohol use. High substance use self-efficacy (SSE) was associated with higher
      alcohol use. Moreover, low GSE was associated with higher SSE. Results indicate
      that alcohol use may be in response to feelings of powerlessness within one's
      life and may be sustained by perceived feelings of control over use. The study
      suggests that the concept of self-efficacy appears to relate to empowerment
      issues and, as such, would have important applications for use with minority
      individuals.

PMID- 10910530
TI  - Development and validation of the Self-Identity Inventory (SII): a multicultural
      identity development instrument.
AB  - The Self-Identity Inventory (SII) was developed using the Optimal Theory Applied
      to Identity Development (OTAID) model. A sample of 325 culturally diverse
      respondents completed the SII, the Tolerance Scale from the California
      Psychological Inventory, the Belief Systems Analysis Scale, and the Social
      Desirability and Infrequency Scales. Through confirmatory factor analysis,
      goodness-of-fit, and social desirability/item infrequency measures, SII items
      were analyzed, resulting in a 6-scale, 71-item inventory. Internal consistency
      for the scales ranged from .72 to .90. Test-retest reliability ranged from .72 to
      .92. Correlations with external construct validity measures supported
      predictions. Interscale correlations and other statistical tests primarily
      supported the OTAID model. Implications for therapy and future research are
      suggested.

PMID- 10910531
TI  - The conception of depression in Chinese American college students.
AB  - The conception of depression in Chinese American college students was examined
      with the Center for Epidemiologic Studies--Depression Scale (CES-D). It was
      hypothesized that, because of their significant engagement with mainstream
      American culture, these students' conception of depression would better
      approximate White Americans' differentiated view (L. Radloff, 1977) than the
      general Chinese American community's integrated view (Y. Ying, 1988). A total of
      353 bicultural Chinese American college students participated in the study.
      Consistent with the hypothesis, principal-components factor analysis with varimax
      rotation revealed a factor structure and loading similar to that found in White
      American adults. Confirmatory factor analysis also showed Chinese American
      college students to better approximate Radloff's differentiated model based on
      her White American samples than Ying's integrated model based on her Chinese
      American community sample. Implications of the findings and directions for future
      research are discussed.

PMID- 10910532
TI  - Effects of racial socialization and racial identity on acculturative stress in
      African American college students.
AB  - The aim of this study was to determine if racial identity mediates the relation
      between racial socialization and acculturative stress in African American
      university students, once demographic factors are accounted for. In a sample of
      84 participants, significant relations were found between racial socialization
      and acculturative stress, racial socialization and racial identity, and racial
      identity and acculturative stress. Partial support for a mediational model was
      found, with the best predictors of acculturative stress being immersion attitudes
      and internalization attitudes.

PMID- 10910533
TI  - Hispanic counselors' race and accent and Euro Americans' universal-diverse
      orientation: a study of initial perceptions.
AB  - This study examined Euro American participants' initial perceptions of male
      Hispanic counselors. Two hundred twelve college students evaluated male Hispanic
      counselors whose race was White, Mestizo (a mix of White European and Native
      American ancestry), or Black and who spoke English with or without a Spanish
      accent. The participants' perceptions were analyzed in the context of their
      scores on universal-diverse orientation, a new theory and measure of
      multicultural awareness (M. L. Miville et al., 1999). Results suggest that
      participants' perceptions of the Hispanic counselors as attractive, expert, and
      trustworthy, as well as their willingness to work with them in long-term therapy,
      were affected by the counselors' race and accent and by the participants' level
      of universal-diverse orientation. These results are discussed in the context of
      relevant literature, and recommendations for future research in this area are
      provided.

PMID- 10910534
TI  - Revenge of the mutant cockroach: culturally adapted storytelling in the treatment
      of a low-income African American boy.
AB  - A clinical case is presented in which a culturally adapted storytelling technique
      was used in child therapy with a socioeconomically disadvantaged African American
      boy. In this intervention, the child and therapist co-created a story by taking
      turns adding to the story during therapy sessions. The child's contributions to
      the story were interpreted by taking into account his sociocultural context, and
      the therapist's responses were adapted to reflect relevant sociocultural factors.
      Advantages of storytelling techniques in child therapy are presented, and issues
      to consider when using these techniques with culturally diverse populations are
      discussed.

PMID- 10910535
TI  - Cytogenetics: from aneuploidy to polymorphism.

PMID- 10910536
TI  - Acid gastro-esophageal reflux in the 10 degrees-reversed-Trendelenburg-position
      in supine sleeping infants.
AB  - Many pediatricians recommend, empirically, the "supine reversed-Trendelenburg
      sleeping position" in infant regurgitation, although its efficacy has not been
      validated. Esophageal pH monitoring data from 10 consecutively investigated
      regurgitating infants show that the acid reflux parameters in all of them were
      increased in the "supine reversed-Trendelenburg position at 10 degrees" in
      comparison to the flat supine sleeping position. We conclude that further studies
      are needed to evaluate the effect of the "supine reversed-Trendelenburg position"
      on reflux parameters before recommending this position as a possible treatment to
      decrease esophageal acid exposure.

PMID- 10910537
TI  - Study of human Y chromosome polymorphism in Taiwan.
AB  - The Y chromosome is one of the human chromosomes carrying significant amount of
      constitutive heterochromatin. To investigate the prevalence of Y chromosome
      polymorphism and its clinical significance in Taiwan, we analyzed the Y
      chromosome among 6,286 unrelated males by G-banding and, if necessary,
      fluorescence in situ hybridization studies. The prevalence of the Y chromosome
      variants were: large Y (Yq+) 3.6%, pericentric inverted Y [inv(Y)] 0.27%, and
      small Y (Yq-) 0.59%, respectively. More than 99% of those variants were from
      their biological fathers. The incidence of the Y polymorphisms was similar in
      three groups: children with mental retardation, other chromosomal aberrations or
      multiple congenital anomalies, and normal controls. The Yq12 heterochromatin
      region may contribute to the variation in Y chromosome length. The prevalence of
      inv(Y) and Yq+ was higher than those in the white population. Our results
      conclude that there are no indications that Yq+, inv(Y) and Yq- are connected
      with any deviations in intelligence or with an increased risk of physical
      malformations or other chromosomal disorders, which is of great help for genetic
      counseling.

PMID- 10910538
TI  - Tuberous sclerosis with visceral organ involvement.
AB  - This study is to determine the incidence of visceral organ involvement in
      tuberous sclerosis (TS). We reviewed 30 cases of TS diagnosed between 1987 to
      1997. There were 17 males and 13 females, ages ranged from one day old to 17
      years old. Among the 30 cases, 25 patients had seizures and skin manifestations;
      24 had cerebral tubercles; 10 had heart involvement (9 rhabdomyoma, 1 dilated
      cardiomyopathy); 4 had kidney involvement (3 polycystic kidney disease, 1 renal
      hamartoma); and 3 had retinal astrocytic hamartoma. Based on our study, the most
      common visceral organs involved were the heart and kidney. Among the ten patients
      with cardiac rhabdomyoma, six were less than 1 year old (mean age 1.6 +/- 2.2
      years old). One newborn presented with a cardiac mass diagnosed by prenatal
      sonography and another newborn, noted to have tachycardia after birth, underwent
      surgical intervention due to impending heart failure. Four patients had kidney
      abnormalities; three were less than 5 years old (mean age 5.2 +/- 5.2 years).
      During this 10 year period, there was no mortality seen among patients with
      visceral organ involvement. We suggest that clinicians treating patients with TS
      should not overlook the visceral organs, especially heart and kidney, which, if
      involved can have significant morbidity.

PMID- 10910539
TI  - Thrombocytosis in children at one medical center of southern Taiwan.
AB  - Thrombocytosis in children is common, but usually without symptoms. The causes of
      thrombocytosis in children are considered to be mostly due to infection, trauma,
      surgery, blood disease, prematurity, renal disease and chronic inflammation. To
      evaluate the incidence and etiology of thrombocytosis of the hospitalized
      patients, patients who were admitted to the Pediatric Department of Kaohsiung
      Medical College Hospital (KMCH) from October 1996 to November 1997 were studied.
      There were 2910 cases studied and 220 cases (127 male and 93 female) had
      thrombocytosis (> or = 500 x 10(9)/L) with a rate of 7.6%. The causes of
      thrombocytosis are infections (49.5%), Kawasaki disease (6.4%), postsplenectomy
      (7.8%), blood diseases (3.7%), malignancies (3.2%), renal disorders (3.2%),
      prematurity (3.2%), tissue damage (4.5%), chronic inflammation (1.8%), recovery
      from marrow suppression (1.3%), immunologic disturbances (2.2%), essential
      thrombocythemia (0.5%), and miscellaneous factors (3.7%). Thrombocytosis
      associated with multiple, simultaneous causative factors was found in 9.0% of
      these cases. Thrombocytosis secondary to infectious diseases or Kawasaki disease
      was significantly more common in children under 2 years old. The most commonly
      associated infectious disease was respiratory tract infection (61.1%). There were
      29 children (13.2%) presenting a platelet count of more than 800,000/mm3.
      However, no thrombotic complications were seen in any of the children. By far,
      the major cause of thrombocytosis in our cases was reactive in character. Most of
      the thrombocytosis cases were due to infections, inflammatory diseases, or
      Kawasaki disease.

PMID- 10910540
TI  - Glucose and insulin infusion versus kayexalate for the early treatment of non
      oliguric hyperkalemia in very-low-birth-weight infants.
AB  - Forty very low birth weight (VLBW) infants with non-oliguric hyperkalemia in the
      first few days after birth were enrolled in this study. They were randomly
      divided into 2 groups, regular insulin (RI) infusion group and kayexalate resin
      enema group. Therapy was administered when serum potassium level was greater than
      6 mEq/L. None of these infants received blood transfusion during this study
      course. In RI group (n = 20), the ratio of infusion glucose to regular insulin
      was 10-15 gm glucose to 1 unit RI, and the glucose infusion rate was maintained
      at least 6 mg/Kg/min. In Kayexalate group (n = 20), the dose of Kayexalate was 1
      gm/Kg body weight given rectally every four hours. All treatment discontinued
      after the serum potassium level returned to normal for 6 hours. The mean
      gestational ages were 27.4 +/- 1.8 weeks in RI group and 28.4 +/- 2.4 weeks in
      Kayexalate group, respectively. Mean birth weights were 935 +/- 259 gm (RI) and
      1065 +/- 214 gm (Kayexalate). The ages at onset of hyperkalemia were 24.6 +/- 8.2
      (RI) and 22.2 +/- 8.1 (Kayexalate) hours after birth. The mean urine outputs
      during the 8-hour interval prior to development of hyperkalemia were 5.4 +/- 1.3
      (RI) and 5.5 +/- 0.9 (Kayexalate) ml/kg/min. The durations of hyperkalemia were
      26.4 +/- 14.9 (RI) and 38.6 +/- 13.3 (Kayexalate) hours. The peak serum potassium
      levels during therapy were 7.3 +/- 0.9 and 7.4 +/- 0.6 mEq/L. The incidences of
      grade II and above intraventricular hemorrhage (IVH) were 15% (3/20) and 50%
      (10/20). The incidences of cardiac dysrhythmia were 5% (1/20) and 10% (2/20).
      Significantly shorter duration of non-oliguric hyperkalemia and lower incidence
      of IVH were noted in RI group, but there were no differences in the peak
      potassium level or the incidence of cardiac dysrhythmia between these two groups.
      We conclude that to use early continuous regular insulin infusion therapy for the
      treatment of non-oliguric hyperkalemia in VLBW infants is more effective than
      kayexalate in decreasing the duration of hyperkalemia and reducing the incidence
      of intraventricular hemorrhage.

PMID- 10910541
TI  - The relation of white blood cell count and atherogenic index ratio of LDL
      cholesterol to HDL-cholesterol in Taiwan school children.
AB  - White blood cell (WBC) count is an independent coronary risk factor in adults. To
      clarify the relation of WBC count and atherogenesity in children, we conducted a
      cross-sectional study in Taiwan from February to June 1996. A total of 3818
      subjects were eligible in the final analyses. The ratio of low to high density
      lipoprotein cholesterol was calculated as atherogenic index. The 75th percentile
      of atherogenic index was calculated and used as cut-off point for high and low
      levels. The mean WBC count in children with high atherogenic index (6.82 x 10(9)
      cells/L) was significantly (p < 0.001) higher than those with low atherogenic
      index (6.58 x 10(9) cells/L). By multiple logistic regression analysis, higher
      WBC count (> or = 7.8 x 10(9) cells/L) was found to be an independent risk
      indicator of atherogenesity (odds ratio: 1.70, 95% confidence interval: 1.20
      2.41) among obese children. Other significant factors associated with
      atherogenesity were gender, obesity, age, triglyceride and total cholesterol
      level. Our results indicate that obese children with higher WBC count have higher
      atherogenic index.

PMID- 10910542
TI  - Eczema herpeticum in children with atopic dermatitis.
AB  - Eczema herpeticum (EH), a form of disseminated cutaneous herpes simplex virus
      (HSV) infection, is a potentially life-threatening disease. It usually occurs in
      individuals with atopic dermatitis (AD) or other preexisting dermatosis. The
      resulting disruption of the skin barrier decreases the ability of such
      individuals to localize an HSV infection. We report eight AD cases with eczema
      herpeticum, seen from February 1989 to January 1996. Their ages ranged from 5
      months to 6 years (mean age 2.5 years), There were 5 boys and 3 girls. Their
      laboratory data showed: IgE: 39 to 474, mean 197 IU/ml; eosinophil count 139 to
      560, mean 314/mm3; Tzanck smear positive in 6 out of 6 patients; vesicle fluid
      culture positive for Herpes simplex type I in 4 out of 4 patients. All patients
      were treated with acyclovir and recovered.

PMID- 10910543
TI  - Rapid diagnosis of common aneuploidies by quantitative fluorescent polymerase
      chain reaction.
AB  - The most frequent autosomal aneuploidies in newborns involve chromosomes 21, 18,
      and 13. The pre- and postnatal detection of chromosome abnormalities has been
      almost exclusively performed by cytogenetic analysis. In this paper, we assess
      the diagnostic value of fluorescent polymerase chain reaction (PCR) using
      polymorphic small tandem repeats (STR). PCR products are distinguished via both
      size and fluorescence intensity to confirm the trisomy by either triallelic
      signals with similar fluorescence intensities or diallelic pattern with double
      dose response. Compared with the relatively time-consuming and laborious classic
      cytogenetic analysis, this technique is rapid, inexpensive, and sensitive for the
      detection of trisomies 21, 18 and 13, particularly when the numbers of cells
      obtained from the prenatal diagnosis is limited or where cell culture fails. With
      greater samples tested and more STR markers available, this method will become
      more reliable. This study investigates the detection of aneuploides involving
      chromosomes 21, 18, and 13 by comparing quantitative fluorescent PCR with
      karyotyping performed by conventional cytogenetics. The results obtained by the
      two techniques were concordant in all trisomy cases of this study.

PMID- 10910544
TI  - Pancreatic tumors in children: report of three cases.
AB  - From 1981 to 1996, we experienced 3 cases of pancreatic tumors in children--two
      pancreatoblastomas (PB) and one solid and cystic tumor (SCT). The ages were 1
      month, 4 years, and 13 years of age respectively. The two cases of
      pancreatoblastoma initially presented as chronic diarrhea with failure to thrive,
      the other case presented with abdominal mass. All of them were studied by
      laboratory examination, ultrasonography, computed tomography and pathology.
      Increasing alpha- fetoprotein (AFP) levels were found in the 2 pancreatoblastoma
      cases, however, the level in the SCT case was normal. Abdominal sonography showed
      pancreatic masses with or without calcification, and the echogenicity may be
      solid and/or cystic. All patients underwent total excision of the tumors. We have
      reviewed the literature and find no pancreatoblastoma with chronic diarrhea was
      reported in young children, especially in neonate. Therefore, we suggest that
      young children presenting with an abdominal mass and/or weight loss should
      undergo imaging studies for the possibility of pancreatic tumors.

PMID- 10910545
TI  - Typhoid fever presenting as infection-associated hemophagocytic syndrome: report
      of one case.
AB  - This report describes a 13-year-old boy who had high fever with severe
      pancytopenia and acute psychosis as initial presentation. Bone marrow examination
      was compatible with infection-associated hemophagocytic syndrome (IAHS). Blood
      culture showed no growth of bacteria while the culture of bone marrow yielded
      Salmonella typhi. The clinical condition stabilized shortly after the use of
      ceftriaxone. This case illustrates that typhoid fever must be included in the
      differential diagnosis of IAHS. In cases with IAHS, bacterial culture as well as
      morphological study of bone marrow is necessary for the evaluation of etiological
      agent and to avoid injudicious use of chemotherapy.

PMID- 10910546
TI  - Intractable wheezing and swallowing problem in an infant: report of one case.
AB  - A 9-month-old female infant with intractable wheezing and frequent aspiration
      pneumonia was poor response to the usual treatment for respiratory disease. The
      barium swallow test revealed barium aspirating into trachea directly. Because of
      the high-risk nature for aspiration in the swallowing disorder infant, a
      nasogastric tube feeding therapy was prescribed. Fortunately, her symptoms were
      greatly reduced. One month later, the clinical and roentgenographic findings
      strongly support a causal relationship between swallowing problem and wheezing.
      Therefore, swallowing problem should be considered when a young infant has
      refractory wheezing, even when there is no developmental problem.

PMID- 10910547
TI  - Kikuchi's disease (histiocytic necrotizing lymphadenitis): report of one case.
AB  - Kikuchi's disease (histiocytic necrotizing lymphadenitis) is a self-limited
      disease of unknown cause. The disease often presents with persistently
      intermittent fever and enlarged cervical lymph nodes. It usually occurs in adult
      group and is unresponsive to antibiotic therapy. The diagnosis can be confirmed
      by histopathological findings of lymph node in open biopsy. We report a pediatric
      case of Kikuchi's disease in an 8-year-8-month-old school-age boy with
      generalized lymphadenopathy. He was hospitalized under the impression of fever of
      unknown origin. A diagnosis of Kikuchi's disease was made by cervical lymph node
      histology. Reviewing the literature of Kikuchi's disease, we found very few
      reports in young pediatric group. We conclude that Kikuchi's disease should be
      considered in the differential diagnosis of fever of unknown origin in children,
      even in the absence of cervical lymphadenopathy.

PMID- 10910548
TI  - Cyanotic congenital heart disease and necrotizing enterocolitis: report of three
      cases.
AB  - Three infants with cyanotic congenital heart diseases (CCHD) had abdominal
      distension, poor activity at day 2, day 3, and day 23. The abdominal
      roentgenograms showed dilated bowel loops, pneumatosis intestinalis, and
      pneumoperitoneum. Necrotizing enterocolitis (NEC) was diagnosed. After medical
      and surgical intervention, one infant survived. In this report, we discuss the
      relationship between CCHD and NEC. The possible risk factors were also discussed,
      and it is recommended that NEC be a considered significant complication of
      infants with CCHD.

PMID- 10910549
TI  - Congenital esophageal stenosis treated with endoscopic balloon dilation: report
      of one case.
AB  - Congenital esophageal stenosis is a narrowing of esophageal lumen that is present
      at birth, and may be asymptomatic in the neonate. Stenosis of the lower esophagus
      is a very rare form of esophageal obstruction. Three types of congenital
      esophageal stenosis have been described: fibromuscular stenosis, membranous webs,
      and tracheobronchial remnants. Fibromuscular stenosis and membranous webs respond
      to dilation, but must be distinguished from strictures caused by peptic
      esophagitis. Tracheobronchial remnants generally require surgical therapy. We
      report a 5-year-old girl with congenital esophageal stenosis, who presented with
      persistent dysphagia and poor weight gain. An esophagogram showed stricture of
      lower esophagus with proximal dilatation above esophagogastric junction. She was
      successfully treated with endoscopic balloon dilation.

PMID- 10910550
TI  - Are intestinal pathogens declining in Taiwan?

PMID- 10910551
TI  - Asymptomatic gross hematuria followed by persistent microhematuria.
AB  - A case of a previously healthy, 13-year-old male with IgA nephropathy is
      presented in order to illustrate clinical onset and differential diagnosis of
      this rather common clinical entity. The laboratory and histopathological
      diagnosis is illustrated and discussed, as well, together with a brief discussion
      of possible pathogenesis. In this disorder, in which approximately 11% of
      affected patients experience spontaneous remission, future development of
      molecular probes to determine prognosis is of great importance.

PMID- 10910552
TI  - Infantile cholestasis--advances in its understanding: new concepts.
AB  - Cholestasis is decrease or absence of bile flow into the duodenum. It can be
      either or in combination pathology of hepatocytes, intrahepatic bile ducts or
      extrahepatic bile ducts. Hepatocyte with their bile secretory apparatus and tight
      junction between hepatocytes are of specific importance in this. Bile is formed
      by several different energy-dependent transport processes. Secretion of bile is a
      complex metabolic process, which depends upon multiple structural and functional
      components in the hepatocytes and bile duct cells. The regulation of bile flow is
      regulated by many hormones. Bile is secreted in bile ducts having pressure of 15
      25 cm of water. Rise in pressure in these bile ducts of more than 35 cm of water
      result suppression of bile flow and jaundice. A rise of conjugated serum
      bilirubin above the value of 400-500 mumol/L finds an alternate excretory pathway
      like urine. Various conditions are responsible for infantile cholestasis and can
      have different outcome of chronic cholestasis. These can be extrahepatic or
      intrahepatic and acute or chronic. Pathological consequences of infantile
      cholestasis are mainly because of malabsorption of fat and fat-soluble vitamins
      and hepatocellular dysfunctions. A battery of tests are required to diagnose the
      early infantile cholestasis. In the management of cholestasis diet rich in MCT is
      needed. Further, a high caloric intake up to 200 kcal/day to get adequate weight
      gain is desirable. Phototherapy, phenobarbitone and rifampicin is helpful in the
      pruritus of cholestasis by enhancing the excretion of bile. Ursodeoxycholic acid
      is specifically helpful in the cholestasis. A number of anti-inflammatory and
      immunosuppressive agents and a new compound, FK 506 has specific role in the
      management.

PMID- 10910553
TI  - Choledochal cyst in infancy: a follow-up study.
AB  - From January 1980 to February 1997, 19 cases, 8 males and 11 females, of
      choledochal cyst were diagnosed before one year old. The majority of patients
      were diagnosed by ultrasonography before 6 months old (15/19; 79%), including two
      diagnosed prenatally. According to Todani's classification, type Ia was the most
      common (74%), followed by type Ic (26%). Fourteen patients underwent Roux-en-Y
      choledocho- or hepatico-jejunostomy and cyst excision, 3 patients underwent Kasai
      operation, and I patient underwent external biliary drainage only. The remaining
      one patient with Trisomy 18 anomaly refused operation. Four of the 10 patients in
      whom liver histologic examinations were performed, had liver cirrhosis. The
      follow-up period of these patients ranged from 6 months to 9 years, with a mean
      of 4.1 years. We divided these 19 cases into 2 groups, according to the presence
      or absence of biliary atresia. In the 7 infants with biliary atresia (37%), all
      presented with jaundice and alcoholic stool. Two patients died due to delayed
      presentation and surgery, both had liver cirrhosis. One patient is living with
      liver cirrhosis. Another patient was lost to follow-up, but frequent cholangitis
      was noted till 8 months old. The remaining 3 patients are living and well. In the
      12 without biliary atresia, 9 patients are living and well. Two patients died,
      one due to Trisomy 18 anomaly and the other with delayed surgery and liver
      cirrhosis. One case was lost to follow-up. In summary: 1-) a possibility of the
      association of biliary atresia in infants with choledochal cyst should be
      carefully searched and considered as a unique group; 2) ultrasonography is a good
      diagnostic tool in choledochal cyst during prenatal or infancy period; 3) the
      mortality cases were characterized by prolonged bile stasis, biliary cirrhosis,
      delayed surgery, or multiple anomalies; 4) surgery should be performed as early
      as possible for those with persistent jaundice and light colored stools.

PMID- 10910555
TI  - Normal values of inner canthal distance, interpupillary distance and palpebral
      fissure length in normal Chinese children in Taiwan.
AB  - Ocular measurements, including inner canthal distance, outer canthal distance,
      interpupillary distance, and palpebral fissure length are important in the
      evaluation of congenital deformities and posttraumatic telecanthus. In this
      research, 4446 normal Chinese children in Taiwan were enrolled in our study. The
      sample of 284 full term neonates, 2742 infants and children aged from 1 month to
      3 years, and 1420 preschool children were measured for inner canthal distance,
      outer canthal distance, interpupillary distance and palpebral fissure length. We
      calculated the mean value and standard deviation of the ocular measurements in
      normal Chinese newborns, infants and preschool children in Taiwan under 5 years.
      No significant sex differences were observed. Compared with previous studies,
      inner canthal distance, outer canthal distance and interpupillary distance in
      Chinese children in Taiwan were wider than those in Caucasian children, but the
      palpebral fissure length was not significantly different. We also found that
      inner canthal distance was wider than palpebral fissure length at the same age;
      therefore it was not correct to diagnose hypertelorism in Chinese children in
      Taiwan; as if an imaginary third eye could fit between the eyes. Thus, we suggest
      that measurements should be adjusted with normal standards specific for race.
      Consideration of the position of eyes is relevant for the diagnosis of a large
      number of syndromes.

PMID- 10910554
TI  - Clinical analysis of a dysentery outbreak in Taichung.
AB  - In September 1993, we collected 207 patients due to dysentery, who visited the
      Department of Pediatrics at China Medical College Hospital. In our report, 67.6%
      of these patients were amebic dysentery, 19.3% were combined infection with
      amebic and Shigella sonnei dysentery, and 13.1% were Shigella sonnei dysentery.
      Therefore, amebic dysentery was the predominant cause during this outbreak. The
      clinical features of this outbreak were, in descending order, watery stool,
      fever, abdominal pain, mucinous stool and bloody stool. No concurrent liver
      abscess was discerned. Because there had not been such a clustering of dysentery
      in Taichung for so many years, we thought that travel to endemic areas might have
      been the underlying predisposing cause. Most of the school water supplying system
      was ground water, which might have been contaminated by a few patients returning
      from endemic areas. We thought that fecal-oral route by contaminated water might
      have been the primary transmission route.

PMID- 10910557
TI  - Guillain-Barre syndrome presenting with severe pain: report of one case.
AB  - Most neurologists are familiar with pain in Guillain-Barre syndrome but some
      pediatricians may still miss or underestimate it. We report a 10-year-old girl
      who presented with headache and numbness in lower extremities. On examination,
      she could walk and showed hyporeflexia, mild muscle weakness, prominent neck
      rigidity and right facial nerve palsy. Headache and pain in neck, low back and
      calves were so severe that she could not fall asleep and the response to
      analgesic was very poor. On 8th day of illness, she needed mechanical ventilation
      and suffered tetraplegia. Symptoms of autonomic dysfunction including
      hypertension and sinus tachycardia appeared thereafter and lasted for a week.
      After receiving a high dose of intravenous immunoglobulin (2 g/kg in 2 days), her
      condition improved gradually although joint pain persisted for about three weeks.
      She could walk unaided by day 40 and run by day 70, and recovered completely 6
      months later. We emphasize that pain in GBS needs proper evaluation and
      management in children as well as in adults.

PMID- 10910556
TI  - Typhoid fever in children: a fourteen-year experience.
AB  - From 1982 to 1995, 71 children admitted in our medical center were diagnosed to
      have typhoid fever by culture or serology. Of the 71 children, most (83%) were
      aged 5-15 years. These children usually presented with fever and gastrointestinal
      symptoms, including abdominal pain, diarrhea, nausea or vomiting, and
      constipation. Hepatosplenomegaly was the most common physical sign observed and
      abdominal tenderness ranked the second. Thrombocytopenia occurring in 9 patients
      (13%) was the most common mode of complication. Other complications included
      intestinal perforation (3%), rectal bleeding (3%), ascites or pleural effusion
      (4%), and meningitis (1%). The incidence of complications tended to be higher
      among children 5 years of age or older (p = 0.31). Most patients responded well
      to appropriate antimicrobial therapies. There was no mortality. Relapse was
      observed in two children, although both had received 10 days of chloramphenicol
      therapy. The clinical isolates of Salmonella typhi were susceptible in vitro to
      all the antibiotics tested, including chloramphenicol, which, however, showed a
      higher MIC90 level than other drugs tested. In conclusion, there were age
      specific differences of typhoid fever in children in terms of the incidence and
      morbidity and antibiotic resistance of S. typhi has not been a problem in this
      area at least up to 1995.

PMID- 10910558
TI  - Carnitine transport defect presenting with hyperammonemia: report of one case.
AB  - Carnitine (beta-hydroxy-gamma-trimethylaminobutyric acid) is involved in the
      transport of long-chain fatty acids into the mitochondrial matrix and removal of
      potentially toxic acylcarnitine esters. Carnitine transport defect is a very rare
      metabolic disease. A 7-month-old female infant was found to have consciousness
      disturbance, hyperammonemia, hepatomegaly and elevated transaminases. Both the
      concentrations of free carnitine and acylcarnitines in her blood were very low.
      The diagnosis of carnitine transport defect was confirmed by assays of carnitine
      uptake and transport in skin fibroblasts. She responded dramatically to carnitine
      therapy, and there was no hyperammonemia attack for more than 3 years. Her
      cardiac function also remained normal.

PMID- 10910559
TI  - Wolf-Hirschhorn (4p deletion) syndrome: report of one case.
AB  - Wolf-Hirschhorn syndrome is an uncommon chromosomal disorder caused by loss of
      material from the distal aspect of the short arm of chromosome 4. Its
      characteristic features include profound growth retardation with psychomotor
      delay, severe mental deficiency, facial dysmorphia, midline defects and skeletal
      anomalies. We herein report a case of 4p deletion syndrome and review related
      literature.

PMID- 10910560
TI  - Toxic megacolon in Salmonella colitis: report of two cases.
AB  - Toxic megacolon is a complication that usually presents in inflammatory bowel
      disease such as ulcerative colitis or Crohn's disease. It also occurs in typhoid
      fever, acute bacillary dysentery, amebic colitis, ischemic colitis,
      pseudomembranous colitis and severe salmonellosis. This report describes the
      occurrence of toxic megacolon in two young children with Salmonella colitis
      manifesting as abdominal distension, diarrhea and fever. The clinical course of
      these two cases suggests that toxic megacolon is a severe complication of
      salmonellosis in children, irrespective of the use of antibiotics. In the light
      of its paucity in children and severity, accurate diagnosis and appropriate
      intensive medical-surgical management is essential.

PMID- 10910561
TI  - Alcohol and other drug use among adolescent students in the Atlantic provinces.

PMID- 10910562
TI  - Closer to home: the case for experiential participation in health reform.
AB  - This article describes partial results from a case study of community
      participation in "New Directions for a Healthy B.C.", a now-abandoned health
      reform policy. For this study, focus groups were conducted to explore the
      perspectives of traditionally under-represented citizens in understanding reasons
      for nonparticipation and to identify strategies for fostering participation in
      the health reform process. The findings indicate that participating in
      traditional ways- committee meetings, public fora, completing surveys--was not
      relevant to the realities of these individuals. Yet, rather than merely refusing
      to be involved, focus group members extended an invitation for health planning
      group members to experience their daily lives; an idea that is referred to in the
      literature as 'experiential participation.' In order to foster broad-based
      participation in community health initiatives, the findings from this study argue
      for a new understanding of, and appreciation for what actually constitutes
      participation.

PMID- 10910563
TI  - Firearm safety courses for elementary school-age children.

PMID- 10910564
TI  - [Epidemic of gastroenteritis of viral origin associated with eating imported
      raspberries].
AB  - Several episodes of food poisoning affected the region of Quebec City in July and
      August 1997. In the first two episodes, the analysis of two cohorts (A and B)
      demonstrated that the consumption of a raspberry mousse with raspberry sauce
      increased the risk of contracting gastroenteritis (A, RR = 2.6 p = 0.001; B, RR =
      4.7 p = 0.02). More than 200 people were sick after eating a raspberry dessert.
      The common ingredient of all those desserts was raspberries imported from Bosnia.
      Viral studies on the raspberry sauce (2) and stool samples (5) using the genome
      amplification method by PCR indicated the presence of genomic material compatible
      with a virus of the Caliciviruses family. Southern hybridization and sequence
      analysis showed that the nucleotide sequences found in the raspberry sauce and in
      the stool samples were identical. It is important to maintain active surveillance
      to detect and limit the spread of this kind of outbreak.

PMID- 10910565
TI  - The role of community organizations in the transformation of the health services
      delivery system in the Montreal metropolitan area.
AB  - In 1995 the Montreal Regional Health and Social Services Board began a major
      process of change to its health care system. This transformation places
      particular emphasis on primary health care and increases the role of local
      community services centres (CLSCs) and community organizations (COs). In order to
      understand this process as experienced by COs, the present exploratory study was
      conducted during the summer and fall of 1996. We targeted 12 COs, 4 CLSCs, the
      Quebec Federation of CLSCs, and the Montreal CLSC Working Group. Semi-structured
      group interviews and CO documents were used as sources of information. Most
      participants believe in the need for change but feel that the strategies and
      implementation have been mismanaged. COs are feeling the pressure to
      professionalize and specialize current and future services. The "social economy"
      appears to be gaining momentum in the health sector.

PMID- 10910566
TI  - Caregiving arrangement and nutrition: good news with some reservations.
AB  - The objective of this study was to assess the impact of caregiving arrangement on
      the iron and folate status of infants and toddlers reared at home or enrolled in
      centre-based, independent home, or licensed home care. One hundred and eighty
      nine children aged 2 to 29 months were assessed 1 month prior to child care entry
      and at 6 months after entry into child care. Dietary (24-hour records),
      anthropometric (height, weight, head circumference) and biochemical (red blood
      cell folate, hematocrit, transferrin, and serum ferritin concentrations) methods
      were used to assess nutritional status. Frequency of illness was determined by a
      series of telephone interviews. Median intake of nutrients exceeded Canadian
      recommendations, regardless of care arrangement. Fifteen of 65 children had
      hematocrit values below age-specific cutoffs at the 6-month post-entry to child
      care visit. Children were frequently taken to obtain medical advice (average of 4
      to 6 times during the study period) and 75% of subjects were prescribed at least
      one course of antibiotics. In conclusion, infants and toddlers in this study were
      generally well nourished, regardless of child care arrangement; however, iron
      status may remain an issue in this sample of infants and toddlers.

PMID- 10910568
TI  - Cancer coverage in mass-circulating Canadian women's magazines.
AB  - Mass media can inform health beliefs and shape cancer control behaviours. This
      study surveyed cancer coverage in 309 issues of Canadian women's magazines for
      the period 1991-1997. Magazines were selected if 1996 revenue > $10 million and
      circulation > 500,000; Canadian Living, Chatelaine, Flare and Homemaker's met
      these criteria. The volume of cancer coverage varied significantly by year and by
      magazine. However, coverage of specific cancers did not reflect their
      contribution as a cause of cancer death in Canadian women. The percentage of
      articles on lung cancer was lower and on breast cancer was higher than the
      percentage of deaths due to these cancers. All magazines had decreased coverage
      of lung cancer in 1997 compared to 1991. National cancer resource agencies and
      research initiatives on breast cancer were infrequently mentioned. These results
      argue for greater partnerships between the media and health educators to enhance
      balanced dissemination of cancer control information to Canadian women.

PMID- 10910567
TI  - Life expectancy at birth at the local level in Ontario.

PMID- 10910569
TI  - How reliable are selected scales from population-based health surveys? An
      analysis among seniors.
AB  - The objective of the study was to assess the internal consistency and test-retest
      reliability of selected scales from four national and provincial surveys used to
      study the health status of community-dwelling seniors. Items on physical
      impairment, psychological well-being, activities of daily living, chronic health
      problems, social support, and stressful life events were selected from these
      surveys and administered in a group of 1,054 seniors, aged 65 and over, living in
      Wellington County, Ontario. Each scale exhibited high internal consistency
      (Cronbach's alpha > or = 0.70) except for the stressful life events and social
      support scales. The intra-class coefficients (rho) for all scales were > 0.80. In
      addition, almost all single items measures used in this study also exhibited high
      test-retest reliability (kappa > 0.80) except for measures of perceived health
      status (kappa = 0.69) and availability of help in crisis situation (kappa =
      0.48).

PMID- 10910571
TI  - [Global health indicators as predictors of mortality in elderly persons: a six
      year prospective study].
AB  - The objective of this prospective study was to determine if certain global health
      indicators can predict the occurrence of mortality in a representative sample of
      the elderly in three age strata, after adjusting for sex. The sample, matched for
      age and sex, comprised 559 subjects. Structured interviews based on the OARS and
      SMAF were used to assess health. The cumulative number of deaths per month was
      then recorded over a six-year period. Cox's multivariate model was used to
      express the relative mortality risk among these three age cohorts using the
      overall health indicators as predictors. The results indicate that these
      indicators are significant predictors of mortality only in the 65-72 age group.
      Several hypotheses are presented to explain this phenomenon: psychological
      adjustment to illness, internalization of prevailing social norms, or a cohort
      and survival effect.

PMID- 10910570
TI  - Optimal health care system.

PMID- 10910573
TI  - Use of seclusion and restraint in psychiatric patients in Harare Hospital
      Psychiatric Unit, Zimbabwe: gender differences.
AB  - OBJECTIVE: To examine the frequency and indications for use of seclusion and
      restraint of psychiatric patients in relation to gender differences and risk
      factors in Harare Hospital Psychiatric Unit. DESIGN: Descriptive study. SETTING:
      Harare Central Hospital Psychiatric Unit, Harare, Zimbabwe. SUBJECTS: 95
      consecutively secluded/restrained patients were recruited for the study. MAIN
      OUTCOME MEASURES: The frequency of seclusion and the characteristics of patients
      secluded/restrained. RESULTS: 54 (56.8%) patients were males and 41 were females.
      They had a median (Q1, Q3) age of 30 (Q1, = 24, Q3 = 36) years. Over two thirds
      (70.5%) of them were aged 35 years or less. The frequency of seclusion and
      restraint was 8.5% (95% CI 6.9 to 10.1) of the population of 1,115 patients
      admitted during the study period. The groups (male versus female) differed
      significantly with respect to marital status; single patients being 4.66 (95% CI
      1.17 to 19.96) times more likely to be males when compared to the
      divorced/separated patients. Male patients were more likely to have been brought
      by police than by their relatives or friends (OR 3.30; CI 1.19 to 9.73; p =
      0.020). CONCLUSION: Seclusion/restraints of psychiatric patients were common in a
      psychiatric unit. Male patients were more likely to be brought by police. Female
      patients resorted more to physically assaulting staff/other patients than did
      male patients.

PMID- 10910572
TI  - Predictors of mortality in children hospitalized with dysentery in Harare,
      Zimbabwe.
AB  - OBJECTIVES: To document the pattern of complications and identify risk factors
      for subsequent mortality in a hospitalized paediatric population during a
      Shigella dysenteriae type 1 epidemic. DESIGN: Hospital based prognostic study.
      SETTING: Paediatric wards in Harare and Parirenyatwa tertiary referral hospitals.
      SUBJECTS: All children aged one month to 12 years admitted to the wards with a
      history of bloody diarrhoea between January 1993 to June 30 1994 were included in
      the study (n = 312). MAIN OUTCOME MEASURES: Patterns of complications and
      predictors of mortality. RESULTS: The peak age group of the patients was 12 to 23
      months. Ninety five children died giving an overall case fatality rate (CFR) of
      30.4% (95% CI, 25.3 to 35.6). One third (n = 107) had haemolytic uraemic syndrome
      (HUS), among whom the CFR was 43%. Other complications included altered
      consciousness (35%), seizures (12%), coma (4.5%), severe dehydration (14%),
      abdominal distention (17%), rectal prolapse (5%) and ileus (6%). In a
      multivariate analysis, temperature < 36 degrees C (OR 2.12; 95% CI, 1.33 to
      3.39), severe dehydration (OR, 1.70; 95% CI, 1.15 to 2.53), hyperkalemia (> 5.5
      mmol/L) (OR, 1.74; 95% CI, 1.01 to 1.97), hyponatremia (< 120 mmol/L) (OR, 1.57;
      95% CI, 1.17 to 2.11), urea (> 8 mmol/L) (OR, 1.74; 95% CI, 1.29 to 2.36), and
      abdominal distention (OR, 1.67; 95% CI, 1.16 to 2.41) were found to be predictors
      of mortality. CONCLUSION: Some of the major clinical and laboratory features
      allowing the early identification of children at increased risk of dying during
      dysentery outbreaks have been delineated. The high fatality associated with
      complicated dysentery highlights the need for preventive strategies which are
      sustainable in the region.

PMID- 10910574
TI  - Pediatric emergency and critical care medicine.

PMID- 10910575
TI  - Pediatric advanced life support providing a better prognosis for near-missing
      child.

PMID- 10910576
TI  - The preliminary result of the training course of pediatric advanced life support.
AB  - To improve the preparedness of health care providers in pediatric resuscitation
      and to evaluate the effectiveness of the Pediatric Advanced Life Support course,
      we followed the standard guidelines of American Heart Association to conduct the
      first 10-hour course of Pediatric Advanced Life Support course in our hospital
      and designed this study. A total of 160 doctors and nurses were enrolled in the
      providers course held on Jan. 11, 1998. A pretest, posttest and survey
      questionnaire were given to each participant. One hundred and twenty-nine
      completed these tests. The average scores were 73.1 for the pretest and 86.8 for
      the posttest. The average scores on the pretest and posttest among doctors (n =
      57) and nurses (n = 72) are 72.6, 86.7 and 73.5, 86.8, respectively (p < 0.001).
      In the participants with pretest score of less than 80 (n = 92), the mean values
      of pretest and posttest scores were 69.0 and 86.4. The participants with pretest
      scores higher than or equal to 80 (n = 37) had pretest and posttest mean values
      of 83.3 and 87.7. The participants with less background knowledge (pretest < 80)
      had better increment scores after this course (p < 0.05). The mean posttest
      scores in those working in private clinics and having 20 years of working
      experience are 74.0 and 72.0 (lower than the criteria for successful completion
      of written examination). We conclude that this provider course did increase the
      knowledge and skill pertaining to pediatric resuscitation personnel, particularly
      in participants with less background knowledge. The participants from private
      clinics or with working experience more than 20 years need a repeatedly
      educational PALS training course.

PMID- 10910577
TI  - Shock in the pediatric emergency service: five years' experience.
AB  - We undertook a retrospective study of the risk factors determining outcome of
      nontraumatic patients with shock in the pediatric emergency service. From October
      1992 through September 1997, 22 patients with the diagnosis of shock were
      identified, including 11 with septic shock (50%), 7 with hypovolemic shock (32%)
      and 4 with cardiogenic shock (18%). Their age ranged from 2 months to 19 years
      old. Among the cases, 14 patients (64%) had other underlying diseases. Gram
      negative bacterial sepsis (6/11, 55%), dilated cardiomyopathy (2/4, 50%) and
      acute gastroenteritis (7/7, 100%) were the most frequent causes of septic,
      cardiogenic and hypovolemic shock, respectively. In total, 12 patients (55%)
      died. The mortality rate was high in septic shock (9/11, 82%) and cardiogenic
      shock patients (3/4, 75%), but low in hypovolemic shock patients (0/7, 0%). The
      risk factors of poor outcome in patients with shock included thrombocytopenia,
      prolonged prothrombin time and partial thromboplastin time. Patients with
      leukopenia, a higher level of C-reactive protein, or under 2 years of age tended
      to have poor outcome.

PMID- 10910578
TI  - Congenital choanal atresia: computed tomographic and clinical findings.
AB  - Congenital choanal atresia is a rare developmental anomaly characterized by
      failure of communication of the posterior nasal cavity with the nasopharynx. It
      may present as a component of the CHARGE association (C, coloboma; H, heart
      disease; A, atresia choanae; R, retarded growth and development; G, genital
      hypoplasia; and E, ear anomalies and/or deafness). The purpose of this study is
      to evaluate the computed tomographic (CT) appearance of membranous or bony type
      congenital choanal atresia. Six patients (4 females, 2 males; age range, 1 day to
      8 weeks; mean, 13.8 days) with choanal atresia were included in this study and
      evaluated by CT scan. The CT clearly delineated the full anatomic abnormalities
      of choanal atresia. Among the 6 patients, three (50%) had bilateral membranous
      atresia, two (33%) had bilateral bony atresia, and one (17%) had unilateral
      (left) membranous atresia. Additionally, two (33%) patients (1 bilateral
      membranous atresia, 1 bilateral bony atresia) fit at least four of the six
      criteria in the CHARGE association. The CT plays a significant role in the
      diagnostic and therapeutic approach to congenital choanal atresia and should be
      the examination method of choice to evaluate neonates with nasal obstruction.

PMID- 10910579
TI  - Sonographic measurements of renal size in normal children and children with
      compensatory renal hypertrophy.
AB  - Renal length and anteroposterior diameter of both kidneys were measured from
      normal renal sonograms of 326 children (aged from newborn to 15 years) and
      graphed to provide a growth chart of normal renal size against age. Mean renal
      lengths are reported for each year of age. The renal size of 20 children with
      single kidney, either congenital or postnephrectomy, were also evaluated. Our
      data showed actual nephromegaly of the solitary kidney indicating compensatory
      renal growth.

PMID- 10910580
TI  - Midterm outcome of mitral valve regurgitation after repair of atrioventricular
      septal defect.
AB  - The purpose of this retrospective study was to evaluate the outcome of mitral
      regurgitation (MR) following repair of atrioventricular septal defects (AVSDs).
      Echocardiograms of all survivors after AVSD surgery between 1991 and 1996 were
      reviewed. This study enrolled 16 patients who had had more than two postoperative
      color Doppler studies. On each echocardiogram, MR severity was graded on a 1+ to
      4+ scale, based on the size of the MR jet. Mean age at surgery was 31.1 months
      (range 2.5 to 83) and mean postoperative follow-up duration was 23.6 months
      (range 1 to 59). Mild deterioration of mitral valve function was common. MR
      severity increased by one or more grades in 5 patients (31%) between the initial
      and final examinations. However, the deterioration in mitral valve function
      occurred primarily on the immediate postoperative stage. On mid-term follow-up,
      the MR improved, or at least became stationary, in all patients. Mitral
      valvuloplasty was not necessary in surviving patients. We conclude that
      postoperative MR remains fairly stable following AVSD repair. Serious
      deterioration is rare.

PMID- 10910581
TI  - Nephrocalcinosis in childhood.
AB  - Charts of 16 children with nephrocalcinosis between 1990 and 1997 were reviewed.
      The cause of nephrocalcinosis was believed to be iatrogenic in 7 patients (43.8%)
      and non-iatrogenic in 9 (56.2%). Vitamin D therapy was responsible for 5 patients
      of iatrogenic nephrocalcinosis, and furosemide therapy for the remaining
      iatrogenic patients. Non-iatrogenic cases consisted of 3 patients with renal
      tubular acidosis, 3 patients with idiopathic hypercalciuria, and the 3 other
      patients with rare underlying conditions. Abdominal X-ray detected
      nephrocalcinosis in only 2 (12.5%) of the total 16 patients. None showed
      resolution of nephrocalcinosis during these years of follow-up.

PMID- 10910582
TI  - Molecular diagnosis of Apert syndrome in Chinese patients.
AB  - Apert syndrome is a clinically distinct condition characterized by
      craniosynostosis and severe syndactyly of the hands and the feet. Apert syndrome
      results from either of two specific nucleotide substitutions, both C-to-G
      transversions, in the fibroblast growth factor receptor 2 (FGFR2) gene. To
      determine if Chinese Apert syndrome patients carry the same mutations, fifteen
      unrelated Apert syndrome patients and a fetus from a mother with Apert syndrome
      were studied by the use of restriction analysis and direct sequencing. The
      results demonstrated that 13 had the Ser252Trp mutation and 2 had the Pro253Arg
      mutation. Prenatal diagnosis of the fetus was successfully made.

PMID- 10910583
TI  - Calcinosis cutis following extravasation of calcium gluconate in neonates.
AB  - Neonatal hypocalcemia is not an uncommon condition, especially in the premature
      neonate. It is effectively treated by intravenous infusion with calcium
      gluconate. We treated nine neonates with subcutaneous calcium deposition
      following calcium replacement with calcium gluconate from Jan. 1997 to Dec. 1997.
      Three of the infants were born to diabetic mothers, two had perinatal asphyxia
      and four were born prematurity. The average dosing number was 7.4 (5 to 9 doses).
      The onset of calcinosis cutis was 5 to 11 days after the first dose. The
      replacement of calcium gluconate caused amorphous masses at the site of
      extravasation and contracture of joint movement. A radiographic study was
      performed to determine the extent and course of extravasation, and areas remote
      from the infusion site also showed calcification. There is no specific mode of
      treatment except supportive management and a skin graft. The patient could
      functionally recover with cosmetic residue. In our follow-up clinics, all infants
      completely recovered without functional limitations.

PMID- 10910584
TI  - Primary splenic lymphoma in a child.
AB  - Primary splenic lymphoma is a relatively rare cause of splenomegaly; its reported
      incidence being less than 1% of non-Hodgkin lymphoma in most reported series. We
      report a 10 year-old boy presenting with a huge splenic mass which was found
      incidentally after an abdominal contusion. Diffuse large cell lymphoma of the
      spleen with no evidence of disease dissemination was proven after tumor
      resection. After surgery and adjuvant chemotherapy, he has remained disease free
      3 years since the diagnosis. The purpose of this paper is to report a rare
      occurrence of primary splenic lymphoma in a child.

PMID- 10910585
TI  - Idiopathic thrombocytopenic purpura preceding malignant lymphoma: report of one
      case.
AB  - Idiopathic thrombocytopenic purpura (ITP) preceding malignant lymphoma is a rare
      condition. Most cases occur simultaneously with lymphoma or after it has been
      diagnosed. The case of a child with idiopathic thrombocytopenic purpura recovered
      after prednisolone treatment, but lymphoma developed four months later. The
      pathogenesis for idiopathic thrombocytopenic purpura evolving into malignant
      lymphoma is still unknown and further study is necessary.

PMID- 10910586
TI  - Prompt recognition of necrotizing fasciitis in a newborn.
AB  - We report a 13-day-old female neonate with necrotizing fasciitis, who presented
      with fever and erythema on her back. Rapidly progressive extension of the
      erythema to the abdominal wall occurred within 12 hours. Sonography for the
      lesion showed extensive fascial thickening with fluid accumulation. An abscess
      was also demonstrated. Necrotizing fasciitis was highly suspected. Under
      sonographic guidance, pus was aspirated from the abscess. A smear for the
      aspirated pus revealed a large number of neutrophils and abundant gram-positive
      cocci. Immediate surgical debridement was done. Cultures from the pus and blood
      revealed Staphylococcus aureus. The patient was free of symptoms after surgical
      debridement and aggressive antibiotic therapy. She had skin grafting to
      reconstruct the debrided wound on the 20th hospital day and was discharged
      shortly after the debridement of wound.

PMID- 10910588
TI  - Isolation of Eikenella corrodens from polymicrobial hepatic abscess: report of
      one case.
AB  - Eikenella corrodens is a rare cause of hepatic abscess. We report a case of a
      hepatic abscess caused by (1) Bacteroides fragilis, (2) Streptococcus
      constellatus and (3) E. corrodens, which illustrates potential problems of
      antibiotic coverage due to the presence of Eikenella species. The infection
      followed an episode of acute gastroenteritis and the clinical course appeared
      indolent evolving over one week. Besides empirical antibiotics, initial
      percutaneous aspiration was performed and yielded pus which grew E. corrodens
      concomitantly with Streptococcus species. E. corrodens was sensitive to
      penicillin but resistant to clindamycin and metronidazole. But B. fragilis was
      resistant to penicillin. So the antibiotics were switched to
      amoxicillin/clavulanate. Unfortunately fever persisted and the abscess increased
      in size. Therefore echo-guided percutaneous drainage with pigtail catheter was
      installed. Fever subsided 5 days later. After 21 days treatment of antibiotics,
      the patient was discharged in good condition despite having some sterile fluid in
      the residual abscess cavity. Two months after discharge the follow-up echogram
      confirmed complete resolution of the residual abscess. This patient shows us the
      existence of E. corrodens in pediatric patients, especially when the hepatic
      abscess is very likely from the spread of an oral or abdominal infection.

PMID- 10910587
TI  - Corneal opacity and congenital glaucoma associated with massive heparan
      sulfaturia: report of one case.
AB  - A four month-old male infant was noted to have had severe corneal opacity since
      birth. Buphthalmos, increased intraocular pressure and corneal opacity with
      neovascularization were noted during physical examination. There was neither
      dysmorphic face nor hirsutism and the liver and spleen were impalpable. In
      addition, hypotonia, poor head control, and absence of Moro and grasping reflexes
      were also noted. There was no evidence of congenital infection by TORCH study.
      Tests of both urine and plasma amino acids were within normal limits. However,
      excessive urinary excretion of heparan sulfate was detected by thin-layer
      chromatography. Corneal transplantation was performed at 6 months old.
      Histopathological examination of the corneal button showed homogeneous thickening
      of Bowmen's membrane and intracytoplasmic pinkish substances in corneal stroma.
      The Alcian blue stain was positive, which was consistent with
      mucopolysaccharidosis of cornea. The manifestation of this case may be a clinical
      variant of Sanfilippo's syndrome (Mucopolysaccharidosis type III).

PMID- 10910589
TI  - Excitatory and inhibitory amino acid levels in the cerebrospinal fluids of
      children with neurological disorders.
AB  - Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children
      with various neurological disorders was performed with high performance liquid
      chromatography (HPLC). Glutamate increased in patients with bacterial meningitis,
      aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis
      and seizure disorders. Glycine increased in both bacterial and aseptic
      meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the
      main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory
      amino acids are richly distributed in brain tissue and are related to neuron
      activity. Changes in amino acid levels in the CSF may reflect the pathologic
      state and severity of brain insults, and may be useful in monitoring disease
      processes. Further study is necessary to determine whether CSF aminos acid levels
      have a role in practical clinical application.

PMID- 10910590
TI  - Congenital duodenal membrane: a ten-year review.
AB  - Traditionally, congenital duodenal membrane (CDM) has been classified as a type
      of duodenal atresia. To provide a better understanding of this disease entity,
      the experience of our 13 patients with congenital duodenal membrane treated from
      April 1988 to November 1998 is reported. Nine were boys and four were girls,
      including four prematures (31%). Late diagnosis was made in eight babies and led
      to prolonged hospitalization (mean 20 days), although duodenal obstruction was
      demonstrated by barium study in all 13 patients. The low frequency of bilious
      vomiting (46%) and abdominal distention (39%), and lack of definite findings on
      plain abdominal X-ray and abdominal ultrasonography, have contributed to the
      delayed diagnosis in our patients. Nevertheless, no major complications developed
      after web excision with duodenoplasty, and satisfactory weight gain was noted in
      all patients except the two with Down syndrome. Since CDM is often overlooked, a
      better understanding of this disease entity can prevent delayed diagnosis, growth
      retardation and prolonged hospitalization.

PMID- 10910591
TI  - Factors affecting the mortality of sick newborns admitted to intensive care
      units.
AB  - In order to provide better understanding of the factors affecting the mortality
      of sick newborns in the Taipei metropolitan area, data of newborns admitted to
      the intensive care units (ICU) were analyzed retrospectively according to the
      hospital type of care. Fourteen of the 19 hospitals with an ICU admitting sick
      newborns joined the data collection: 3 were local hospitals, 7 were regional
      hospitals and 4 were medical centers. Perinatal and neonatal data of 1083 sick
      newborns were analyzed: 60% were premature newborns and 58% were male newborns.
      The maternal referral rate was 7.8% and the neonatal transport rate was 36.2%.
      Fifty-nine percent of very low birth-weight newborns and 66% of extremely low
      birth-weight (ELBW) newborns were admitted to the medical centers. The two most
      common illnesses were perinatal asphyxia and respiratory distress syndrome. About
      40% needed assisted ventilation. There were higher incidence of maternal
      referral, fetal distress, resuscitation in the delivery room, perinatal asphyxia,
      and necrotizing enterocolitis; lower incidence of meconium aspiration syndrome,
      sepsis and pneumothorax in newborns admitted to the medical center than those
      newborns admitted to other hospitals. A total of 153 newborns (14%) died. The
      most common cause of death was sepsis (22.9%). Multivariate logistic regression
      analysis revealed that factors significantly related to the mortality were
      gestational age < 28 weeks, congenital anomaly, sepsis, resuscitation in the
      delivery room, neonatal transport, congenital heart disease, hospital type of
      care, ELBW, pneumothorax and high-risk pregnancy. The results of the study stress
      the importance of regionalization of perinatal and neonatal care, organization of
      neonatal transport system, newborn resuscitation training, infection control, and
      delicate ventilatory care in the further improvement of the outcome of sick
      newborns in the Taipei metropolitan area.

PMID- 10910592
TI  - Group B Streptococcal infection in neonates: an 11-year review.
AB  - Group B Streptococcal (GBS) infection is an important cause of infant morbidity
      and mortality. The purpose of this study is to evaluate the incidence, clinical
      characteristics, mortality and complications of this infection. From 1985 through
      1995, 66 infants with early onset disease (EOD) and 23 infants with late onset
      disease (LOD) were treated at Mackay Memorial Hospital (MMH). The occurrence rate
      of EOD was 3.26-10.08/1000 admissions. The incidence of the disease was 0.11
      1.39/1000 live births. Of the 66 EOD infants, 24 (36%) were preterm infants.
      There were 33 (50%) infants in EOD category with respiratory distress and 40
      (60%) infants with sepsis. Among the 23 LOD infants, 3 (13%) were preterm
      infants. There were 6 (13%) infants in LOD category with respiratory distress and
      16 (69%) with sepsis. Nine (13%) EOD infants and 14 (60%) LOD infants had
      meningitis. Leukopenia occurred in 24 (36%) EOD infants and 5 (21%) LOD infants.
      Twelve (18%) EOD infants and 9 (39%) LOD infants had a history of prolonged
      rupture of membrane (PROM). The mortality rate was 14% in EOD and 4% in LOD
      infants. Four (17%) LOD infants developed neurological seguelae. Clinically, EOD
      infants were often premature and prone to develop sepsis, respiratory distress
      and leukopenia, while LOD often presented with meningitis and sepsis. Our
      estimated occurrence rate and incidence of EOD were similar to the European
      estimates. The influence of prenatal measures on EOD and the meaning of PROM on
      LOD need further evaluation.

PMID- 10910593
TI  - Influence of perinatal factors on limit of viability in extremely low birth
      weight infants.
AB  - This retrospective study investigated the influence of perinatal factors on the
      limit of viability in extremely low birth weight (ELBW) infants. From January
      1997 to May 1998, all infants weighing less than 1000 gm admitted to NICU of
      China Medical College Hospital were enrolled in this study. Still-born infants
      and infants with congenital anomaly were excluded. The end outcome was survival
      of the infants (defined as alive at discharge). Eighty-four infants were included
      in this study. Their mean gestational age (GA) was 25.8 +/- 1.76 weeks, mean
      birth weight (BW) was 772 +/- 114 gm, and overall survival rate was 48.8%. The
      smallest intact survival was a female infant of GA 23 weeks and BW 530 gm. Early
      neonatal mortality rate (< 7 days) was 26.2% (23/84). The cut off levels, below
      which mortality significantly increased, were GA < 24 weeks and BW < 700 gm (odds
      ratio, 6.11, confidence interval, 2.01 to 18.63 for GA; odds ratio, 2.65,
      confidence interval, 1.09 to 6.39 for BW). The two most significant factors which
      independently affected neonatal survival were GA < 24 weeks and early neonatal
      dexamethasone treatment for the prevention of chronic lung disease (odds ratio,
      9.24, confidence interval, 2.53 to 33.76 for GA; odds ratio, 35.83, confidence
      interval, 7.03 to 183 for dexamethasone treatment). We conclude that in order to
      further reduce neonatal mortality, efforts should be made in the areas of
      prenatal care and women's health to prevent extreme prematurity and low birth
      weight infants. In the case of an impending delivery of an ELBW infant, an active
      plan of management for all gestations > or = 24 weeks seems appropriate. Finally,
      unless it is proven to be safe, early neonatal dexamethasone treatment for
      prevention of chronic lung disease should not be routinely used in ELBW infants.

PMID- 10910594
TI  - Infants of twin pregnancies with one twin demise in the uterus: a retrospective
      study.
AB  - Many papers have reported that twin pregnancies with one twin demise in the
      uterus can cause complications in the surviving twin. We retrospectively reviewed
      charts from 1988 to 1997 at our hospital and found 17 of 302 twin deliveries with
      one twin intrauterine fetal death. The incidence of intrauterine death of a
      single twin was 5.7%. Six of the surviving twin (35.3%) had renal function
      impairment. One died due to acute renal failure. The other five patients
      recovered normal serum creatinine level. Five patients (29.4%) had abnormal brain
      imaging findings. One had multicystic encephalomalacia and microcephaly. Three of
      the five patients were complicated with cerebral palsy. After dividing the
      patients into complicated (n = 8, 47.1%) and non-complicated (n = 9, 52.9%)
      groups, we found that the patients with complication had lower Apgar score at 5
      minutes and those with monochorionic diamniotic placenta had higher incidences of
      complication (62.5% vs 12.5%). We conclude that twin pregnancies with one fetal
      demise in the uterus do result in a higher incidence of complication in the
      surviving twin, especially if placentation type is monochorionic diamniotic. In
      managing the surviving twin of the monozygous twin pregnancies with one fetal
      demise in the uterus, we must be careful to monitor these patients. If
      complication was suspected, we should arrange the brain and kidney
      ultrasonography and manage these patients appropriately to decrease the
      complication risk.

PMID- 10910595
TI  - Clinical experience of ketogenic diet on children with refractory epilepsy.
AB  - Thirteen children with refractory epilepsy received a ketogenic diet (medium
      chain triglyceride oil diet) as an alternative therapy since September 1997.
      Their seizure patterns included (1) generalized tonic-clonic seizures, (2)
      myoclonic seizures, (3) generalized tonic + atonic seizures, (4) complex partial
      seizures, (5) generalized clonic + atonic + myoclonic seizures, (6) head nodding
      + myoclonic + gelastic seizures, and (7) generalized tonic-clonic + myoclonic +
      atonic seizures. Major concerns emphasized on the efficacy and side effects of
      the diet. Clinical observation one month after the diet revealed that 53.8% of
      the patients had a > 75% reduction in seizure frequency and 76.9% of the patients
      had a > 50% reduction in seizure frequency. Six patients had some degrees of
      improvement in cognitive function and/ or school performances. The most common
      side effects were body weight loss (n = 6) and diarrhea (n = 5). Others included
      bad temper (n = 1), abdominal cramps (n = 2), nausea (n = 2), bad body smell (n =
      1), and renal stones (n = 1). Even after discontinuation of the diet, 61.5% of
      patients still had a > 50% reduction in seizure frequency. We concluded that the
      ketogenic diet deserves a trial in children with refractory epilepsy.

PMID- 10910596
TI  - The significance of early subtle coronary arterial lesions on echocardiogram in
      Kawasaki disease.
AB  - Intensive echocardiographic studies were undertaken in 37 patients with Kawasaki
      disease (KD) and 12 febrile controls during the acute stages. Video-tape
      recordings were read doubly-blinded by 3 pediatric cardiologists at 2 hospitals.
      Three characteristics of subtle coronary arterial lesions, including contour of
      lumen, smoothness of endothelium and sono-homogeneity of the surrounding tissue
      were particularly described. Seven of the 37 KD patients (19%) were found to have
      coronary arterial aneurysms (CAA) at the end of the convalescent stage. The 3
      cardiologists agreed in the diagnosis of the subtle lesions by 72%. More patients
      with Kawasaki disease were found to have an irregular endothelium than the
      controls (P < 0.001). KD patients later complicated with CAA were more likely to
      have had the three characteristics of subtle coronary lesions during the acute
      stage than the KD patients without aneurysms (P < 0.001). Also, the coronary
      arterial size measured during the acute stage were found to be positively
      correlated with their largest dilatation at the convalescent stage (P = 0.0001, r
      = 0.61). We conclude that early subtle coronary arterial lesions can herald the
      development of coronary arterial aneurysms.

PMID- 10910597
TI  - Clinical observations of erythema multiforme in children.
AB  - Erythema multiforme (EM), a cutaneous or mucocutaneous disorder, occurs primarily
      in young adults. To evaluate the precipitating factors, clinical courses, and
      treatment of this disease in children, 30 cases aged from 1 month old to 15 years
      of age were studied retrospectively from Jan 1988 to Aug 1998. Twenty-three cases
      were diagnosed as minor type; the other 7 were of major type (Stevens-Johnson
      syndrome). Mycoplasma infection was identified in 4 patients, and adenovirus in
      one patient with EM minor. Cytomegalovirus was found in one EM major patient.
      Anticonvulsant administration before the skin lesions were recorded in 5 EM major
      patients and 2 EM minor patients. All cases received supportive treatment during
      admission. Besides, 6 of 7 patients with EM major, and 11 of 23 EM minor (Group
      A) received systemic corticosteroid at a dose equal to prednisolone 1-2 mg/kg/day
      for 3-14 days. One EM major patient and 11 patients with EM minor (Group B)
      received supportive care only. One EM minor patient with acute idiopathic
      thrombocytopenia purpura was treated with intravenous immunoglobulin. The mean
      duration of course of EM minor was 11.8 +/- 2.9 days, and it was 25.1 +/- 9.8
      days for EM major. No mortality and no sequelae were noted. The average disease
      course and hospitalization time were not significantly different between Group A
      and B: (11.4 +/- 3.1 days vs 12.4 +/- 2.9 days, p = 0.45); (5.4 +/- 2.0 days vs
      6.3 +/- 3.1 days, p = 0.47). This study demonstrated that infections, especially
      mycoplasma, and anticonvulsants play important roles in childhood EM. The skin
      lesions of EM minor subsided within 2 weeks, and EM major recovered completely
      within 6 weeks. Systemic corticosteroid may be beneficial to EM major, but
      probably is unnecessary for patients with EM minor.

PMID- 10910598
TI  - Adult type anomalous origin of the left coronary artery from the main pulmonary
      artery: report of one case.
AB  - Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA
      syndrome) is a rare disease. Most of the cases suffer from myocardial infarction,
      congestive heart failure or even death during the early infantile period, and
      thus are called "infantile type". We present one five-year-old girl with ALCAPA
      syndrome, adult type, who was initially suspected to be a case of atypical
      Kawasaki disease (KD) complicated with coronary arterial aneurysms. Due to
      persistent dilatation of the coronary artery after medical treatment for one year
      and a turbulent flow noticed between the left coronary artery (LCA) and the main
      pulmonary artery (MPA), cardiac catheterization was arranged. The diagnosis was
      established from the coronary cineangiography in spite of a direct connection
      between the aorta and LCA revealed from the echocardiogram. Thereafter open heart
      surgery was undertaken. Diagnosis of ALCAPA syndrome can be made by
      echocardiogram, but this is not fully satisfactory. Selective coronary
      cineangiography remains the definitive diagnosis. Although the patients of adult
      type are more asymptomatic, surgical correction should be undertaken as soon as
      the diagnosis is established since a substantial risk is still present.

PMID- 10910600
TI  - Purpura fulminans in children: report of two cases.
AB  - Purpura fulminans, usually seen in previously healthy children acquiring severe
      infections, especially meningococcal sepsis and meningitis, is a rare
      catastrophic disease with initial hemorrhagic skin lesions rapidly progressing to
      gangrene accompanied by shock and frequently resulting in death. We report 2
      cases of purpura fulminans who were diagnosed in the past 2 years. Both blood
      cultures yielded Neisseria meningitidis. One of them expired within 48 hours
      after admission despite aggressive therapy. The second patient, who received the
      treatment of heparin, antibiotics, and blood product replacement, survived with
      minimal sequelae. We deem young age and severe coagulopathy are especially
      associated with a fatal outcome in children with purpura fulminans. Early
      recognition of this disease and prompt appropriate therapy may be lifesaving for
      these patients.

PMID- 10910599
TI  - Endophthalmitis as a complication of meningococcal meningitis: report of one
      case.
AB  - Metastatic meningococcal endophthalmitis, although rare, is a rapidly progressive
      and sight-threatening infection. We present a 10-month-old infant with
      meningococcal meningitis who developed unilateral metastatic endophthalmitis. If
      patients develop a sepsis-like picture with cloudy cornea and purulent
      conjunctivitis, we have to consider the possibility of endophthalmitis and full
      ophthalmological evaluations are indicated. Treatment should be started as early
      as possible. The outcome of endophthalmitis is frequently permanent visual
      impairment. Endophthalmitis is a true medical emergency requiring early
      antibiotic therapy with full dose of antimicrobials to avoid morbidity and
      blindness.

PMID- 10910601
TI  - Aneurysm of the ascending aorta in a neonate.
AB  - Aneurysms of the thoracic aorta rarely occur in children. We present a female
      neonate who was referred to our hospital due to a heart murmur associated with
      cough and fever at 22 days of age. Both the echocardiography and aortography
      displayed an aneurysm of the ascending aorta at the aortic root. A patent ductus
      arteriosus (PDA) flow was detected on admission but it was not detectable when
      she was 3 months old. Neither physical characteristics of Marfan nor Turner
      syndrome were found, but she has had a huge cutaneous hemangioma over the right
      trunk since birth. The aneurysm did not progress during one year of follow-up.
      The etiology might be idiopathic or medial agenesis. Surgery will be warranted
      only if the aneurysm enlarges.

PMID- 10910602
TI  - Diagnosis of anomalous innominate artery syndrome by spiral CT with 3D
      reconstruction of the airway: report of one case.
AB  - Stridor in infants is a symptom that indicates partial obstruction of the large
      airways. Vascular rings are an unusual cause of tracheal compression which can
      induce stridor in infants and children. We report a 4-month-old boy with
      recurrent wheezing and stridor for 2 months. Spiral computed tomography (CT) and
      three-dimensional (3D) reconstruction aided in the diagnosis of external
      compression on the trachea by an innominate artery. Successful relief of the
      airway's obstruction was achieved by aortopexy. Three months after surgery, he
      was symptom free without any medication.

PMID- 10910603
TI  - Leukocyte adhesion deficiency disorder: report of one case.
AB  - In this paper, a case of leukocyte adhesion deficiency disorder confirmed by flow
      cytometry and leukocyte chemotaxis assays is reported. The 32-day-old female
      infant was admitted to our ward on account of delayed umbilical cord detachment
      and omphalitis. After admission, hemogram revealed severe leukocytosis (white
      blood cell (WBC) counts: 86,800/cumm), and there was poor clinical response to
      several kinds of antibiotics. The above history indicated that the patient might
      be a case of leukocyte adhesion deficiency disorder. A definite absence of
      CD11b/CD18 adhesion molecule on the patient's granulocytes and severe defects of
      leukocyte function demonstrated by chemotaxis, chemokinesis and zymosan-induced
      respiratory burst assays confirmed this diagnosis.

PMID- 10910604
TI  - Recent advances in the understanding of childhood asthma.
AB  - The worldwide increase in diagnosed cases of asthma in the last 15 years, in
      spite of the better understanding of the pathogenesis of the disease and the
      availability of more potent bronchodilators and anti-inflammatory agents, has
      been the concern of clinicians worldwide. For pediatricians, it is most
      disturbing to learn that asthma is the most common chronic disease in childhood.
      In addition, asthma hospitalization rates are highest among children, and death
      rates from asthma are among the highest irrespective of ethnic background in U.S.
      This article will review recent advances in the link between respiratory
      syncytial virus and asthma and discuss modified national guidelines for the
      diagnosis and management of asthma pertinent to care for childhood asthma, as
      well as current thought on allergen immunotherapy in children with asthma. A
      brief perspective is added on the future trend of asthma research. It is hoped
      that these issues will provide incentives for further efforts in childhood asthma
      research.

PMID- 10910605
TI  - Diagnosis of the congenital urethral anomalies of male child by voiding
      cystourethrography.
AB  - Congenital urethral anomalies in boys are rare. This report concerns seven
      children with congenital urethral anomalies other than hypospadias from March
      1995 to February 1998. Seven cases of congenital urethral anomalies were
      diagnosed by voiding cystourethrography (VCUG) from 1246 examinations of boys
      over a period of three years. There were four posterior urethral values, one
      anterior urethral valve, one anterior urethral diverticulum, and one
      megalourethra. Five of them had vesicoureteral reflux (VUR). Two cases of
      posterior urethral valve had renal failure in spite of surgery. Three cases
      exhibited renal cystic dysplasia. The clinical presentation and imaging findings
      are presented. Conventional fluoroscopically monitored VCUG is the principal
      examination used for bladder and urethra study in children. Therefore, in boys
      presenting the signs and symptoms related to voiding disturbance, VCUG is used to
      detect not only VUR but also anomalies in the bladder and urethra. In conclusion,
      VCUG is safe and essential for diagnosis of congenital urethral anomalies.

PMID- 10910606
TI  - Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in
      healthy adolescents on two-dose schedule.
AB  - This is an open, randomized study to compare the immunogenicity and
      reactogenicity of two recombinant hepatitis B virus (HBV) vaccines. The HBV-NF is
      a new formulation with a new adjuvant phenoxyethanol which replaced the
      conventional adjuvant of a commercially available recombinant HBV vaccine
      (Engerix-B). These two vaccines had the same 20 micrograms hepatitis B surface
      antigen (HBsAg). They were administered to the deltoid muscle of 116 healthy
      adolescents, aged between twelve and eighteen years, according to the 0, 6-month
      schedule. Serum was taken at month 0, 1, 6, and 7. Antibody to HBsAg was tested
      by radioimmunoassay. Geometric mean titers of both vaccines displayed no
      significant difference at month 1, 6, and 7. Following the second dose of
      vaccine, the seroprotection titer (10 mIU/ml) rates at month 7 were 90.9% in HBV
      NF and 93.4% in Engerix-B, respectively (p = 0.43). The incidences of local and
      general adverse reactions were from 3% to 7% without significant difference
      between the two vaccines and the reactions were all mild and tolerable. Based on
      this study, regimens of this two-dose schedule proved to be safe and immunogenic,
      which may provide a cost-effective alternative for HBV mass vaccination program
      in adolescents.

PMID- 10910607
TI  - Comparison of immunogenicity of simultaneous and nonsimultaneous vaccination with
      MMR and JE vaccine among 15-month-old children.
AB  - To evaluate the immunogenicity of measles- mumps- rubella (MMR) vaccination with
      Japanese encephalitis (JE) vaccine nonsimultaneously and simultaneously, 145
      babies, aged 15 months were enrolled into two groups. Group A received MMR and JE
      vaccines nonsimultaneously at an interval of 6 weeks; group B received the
      vaccinations simultaneously. Antibody titers of MMR and JE were detected before
      and 8 weeks after vaccination. A total of 118 babies (61 in group A; 57 in group
      B) completed the study. In group A, mean increments of logarithmic geometric mean
      titers (GMTs) of MMR and JE were 4.51, 5.93, 4.07 and 1.99; seroresponse rates
      were 100% (61/61), 77.05% (47/61), 96.72% (59/61) and 59.02% (36/61)
      respectively. In group B, mean increments of logarithmic GMTs of MMR and JE were
      4.35, 5.37, 4.44 and 1.93; seroresponse rates were 98.25% (56/57), 77.19%
      (44/57), 98.25% (56/57) and 57.89% (33/57) respectively. There were no
      significant differences between these two groups. These results suggest that
      simultaneous and nonsimultaneous vaccination with MMR and JE vaccines were
      similar in immunogenicity.

PMID- 10910608
TI  - Effect of local massage on vaccination: DTP and DTPa.
AB  - We previously demonstrated that local massage for one minute can enhance
      immunogenicity of diphtheria, tetanus, and whole-cell pertussis (DTPw)
      vaccination. This study further analyzes the effects of more intense local
      manipulation on infants after DTPw and DTPa (diphtheria, tetanus, and acellular
      pertussis) vaccination. A total of 808 infants aged two months were recruited to
      be vaccinated with either DTPw or DTPa. Vaccinees in both groups were further
      divided into two groups; those receiving local manipulation (massage and hot
      packing after vaccinations) and those receiving only vaccinations. Results showed
      that safety profiles were largely similar between those who had local
      manipulation following vaccination and those without. The only significant
      difference was more frequent local reactions including pain and swelling
      following the first two doses in both the DTPa and DTPw groups receiving
      manipulation compared with the groups not receiving manipulation. Serologic tests
      revealed that local manipulation had no significant effect on antibody response
      to pertussis toxin and filamentous hemagglutinin, and diphtheria and tetanus
      toxins. The effect of local massage on DTPw was related to the intensity of local
      massage. Too vigorous a local manipulation caused adverse local reactions and no
      beneficial effect on antibody response. As for the infants receiving DTPa and
      local massages for two minutes with hot packing, no significant effect on either
      the reactogenicity or immunogenicity was found.

PMID- 10910609
TI  - Radiographic presentation of pulmonary tuberculosis in young children.
AB  - Ten cases of pulmonary tuberculosis (TB) with the isolation of Mycobacterium
      tuberculosis in patients under 6 years of age occurring between July 1994 and
      June 1998 were retrospectively reviewed. Radiographs showed air-space
      consolidation (n = 4), micronodular (n = 3) and miliary lesions (n = 1). Two
      patients showed non-specific bronchopneumonic infiltrations. Other uncommon
      radiographic findings include pneumatocele formation and pleural effusion.
      Lymphadenopathies were detected in 6 (60%) cases using chest radiographs or
      computed tomography (CT), commonly with involvement of the paratracheal and hilar
      lymph nodes. However, most lymph node enlargement was not noted in routine
      postero-anterior (PA) radiographs and usually required a chest CT scan for
      confirmation. Since lymphadenopathy is common in children with pulmonary TB in
      Taiwan, we suggest using chest CT scans to detect such pathology in cases of
      suspected TB if other diagnostic tests are not conclusive.

PMID- 10910610
TI  - A follow-up study of systemic-onset juvenile rheumatoid arthritis in children.
AB  - We analyzed the clinical and laboratory features, treatment, and course of twenty
      one children with systemic-onset juvenile rheumatoid arthritis (S-JRA)
      encountered at our institution over the past ten years. There were eleven boys
      and ten girls. The mean age at onset was 11.6 +/- 4.2 years. The mean duration of
      symptoms prior to diagnosis was 5.5 +/- 1.7 months, and the mean follow-up period
      was 45.7 +/- 9.5 months. The clinical and laboratory features at presentation
      were similar to previous reports, except that peripheral blood smear revealed
      toxic granulation of neutrophils in 60% of our patients. Although systemic
      manifestation could be readily controlled by non-steroidal anti-inflammatory
      drugs (NSAIDs) with or without additional steroids, nine patients suffered from
      chronic arthritis (duration > 6 months) requiring disease-modifying anti
      rheumatic drugs (DMARDs). Of the nine children with chronic arthritis, six (67%)
      had a monocylic systemic course, and seven (78%) had polyarticular disease (five
      or more joints affected) at the disease onset. Five patients developed severe
      destructive polyarthritis, with persistent anemia, thrombocytosis, elevated serum
      C-reactive protein (CRP) levels, and marked functional limitation during follow
      up. One of the five patients with severe arthritis developed systemic lupus
      erythromatosis after 8-year follow-up, and died of sepsis. Our study indicated
      significant morbidity in children with S-JRA in Taiwan.

PMID- 10910611
TI  - Intraarticular triamcinolone hexacetonide injection in children with chronic
      arthritis: a survey of clinical practice.
AB  - To assess the efficacy of the intraarticular steroid(IAS) injection in the
      management of arthritis and the possible related complications in children with
      chronic arthritis. We evaluated 11 children of chronic arthritis (4 girls and 7
      boys), age of onset ranged from 2-13.6 years, who had persistent arthritis
      treated with IAS from November 1994 to June 1997. The results of injections
      showed that the beneficial effect was noted within one day to 2 weeks without
      significant adverse reactions, remission exceeding 6 months was seen in 10 of 11
      patients (in 14 of 18 joints). According to subgroups of chronic arthritis, the
      remission rate of IAS injection in children with pauciarticular arthritis reached
      100%. A significant fall in C-reactive protein (CRP) between pre- and post-IAS
      injection (p = 0.03), but there were no differences in hemoglobin (Hb), white
      blood cells (WBCs), thrombocytes (Plts), erythrocyte sedimentation rate (ESR) and
      osteocalcin level. No injection-related complications were found. In conclusion,
      the IAS injection was an effective and safe treatment in children with chronic
      arthritis with no obvious complications especially in pauciarticular arthritis.

PMID- 10910612
TI  - Nonfunctioning pancreatic tumor manifestated as abdominal mass in a child.
AB  - This report concerns a 9-year-old girl with a nonfunctioning pancreatic tumor
      presented as an abdominal mass. An encapsulated tumor, measuring approximately 8
      x 7 cm, was found during operation, and debulking surgery was done.
      Histopathologic studies proved that it was a pancreatic tumor, compatible with
      non-functioning islet cell tumors. She displayed neither clinical picture of
      jaundice, nor excessive hormonal manifestations such as diarrhea or flushing. No
      evidence would suggest its association with multiple endocrine neoplasia type I.
      To our knowledge, it has never been reported in children in Taiwan.

PMID- 10910613
TI  - Spondyloepiphyseal dysplasia congenita: report of one case.
AB  - Spondyloepiphyseal dysplasia (SED) congenita is a rare disorder with autosomal
      dominant inheritance which demonstrates short stature since birth and displays
      progressive involvement of the spine and the epiphyses of long bones. We present
      a case of SED congenita with short stature since birth, flat midface, short neck,
      barrel chest with pectus carinatum, lumbar lordosis, myopia without retinal
      detachment, and flat, avoid-shaped vertebral bodies. Neurological examination is
      normal. No specific biochemical change or intellectual impairment can be
      discerned.

PMID- 10910614
TI  - Multiple pterygium syndrome: report of one case.
AB  - Multiple pterygium syndrome is a rare autosomal recessive disease which is
      characterized by multiple pterygium across the major joint and other associated
      anomalies. In this article, we report a male premature infant who was born with
      bizarre appearance: mask face with low set ear and micrognathia; pterygium of
      neck, antecubital, popliteal and intercrural area with four extremities flexion
      contracture. He was thought to be the first case report in Taiwan. Besides, we
      review medical literature about this disease.

PMID- 10910615
TI  - Esophageal foreign body presenting with stridor: report of one case.
AB  - We report a case of a 12-month-old infant who developed acute respiratory
      distress with stridor from an impacted proximal esophageal foreign body. She was
      treated inappropriately as upper respiratory infections prior to the validation
      of the presenting complaint. Difficulties in diagnosis of esophageal foreign
      bodies arise, when the patient presents with atypical symptoms. Clinical
      suspicion remains the most important aid to diagnosis and endoscopic examination
      is essential for the diagnosis and successful management of foreign bodies in the
      esophagus.

PMID- 10910616
TI  - Transient hypothyroxinemia of very low birth weight infants.

PMID- 10910617
TI  - Helicobacter pylori infection.
AB  - Helicobacter pylori colonizes the stomach of man, especially during childhood.
      However, H. pylori strains are not created equal, with major differences in
      virulence factors such as the vacuolating cytotoxin A and the cytotoxic
      associated gene A, probably accounting for different clinical symptoms. The
      majority of infected subjects remain asymptomatic. Symptoms are aspecific.
      Helicobacter pylori infection is correlated with socioeconomic conditions and
      hygienic circumstances, resulting in an extremely high prevalence in children in
      developing countries. The golden standard technique to diagnose Helicobacter
      infection is culture of gastric biopsies; specificity and sensitivity of serology
      are low during childhood. Carbon-13 urea breath tests are a useful in the
      diagnosis but especially during follow-up. Recommended treatment consists of
      proton pump inhibitors in combination with two antibiotics out of amoxycillin,
      clarithromycin and metronidazole. The importance or clinical relevance of
      Helicobacter infection in asymptomatic individuals remains to be determined.

PMID- 10910619
TI  - Community-acquired Pseudomonas aeruginosa bacteremia and sepsis in previously
      healthy infants.
AB  - Pseudomonas aeruginosa bacteremia, or sepsis, often occurs in hospitals,
      affecting mainly children with underlying problems. However, it can also appear
      in communities, and affects infants and children without underlying diseases. We
      report eight cases of Pseudomonas aeruginosa bacteremia, or sepsis, in previously
      healthy infants over a three-year period. All patients were less than twelve
      months old and the majority presented with sepsis, diarrhea, ecthyma gangrenosum,
      and neutropenia. The infection route may have been the gastrointestinal tract.
      Concomitant gastrointestinal infections may have played a role in pathogenesis.

PMID- 10910618
TI  - Correlations of serum lipids, uric acid, and albumin among mothers, offspring,
      and siblings in Taipei, Taiwan.
AB  - The purpose of this study was to investigate the correlations of serum lipids,
      uric acid, and albumin, among mothers (n = 111), offspring (n = 208), and
      siblings (n = 57) in Taipei, Taiwan. Analytical items included serum
      triglyceride, serum total cholesterol, high-density lipoprotein cholesterol, low
      density lipoprotein cholesterol, uric acid, and albumin. Statistical analysis was
      performed according to the SAS UNIVARIATE procedure; while regression
      coefficient, parent-offspring regressions, paired-comparison and heritability
      were estimated. These results show higher heritabilities of four types of serum
      lipids, uric acid and albumin between mothers and testers (bYX) or siblings (bZX)
      by parent-offspring regression analysis. Regression coefficients (bYX) of six
      characters were significantly different (p < 0.05-0.01). Regression coefficients
      (bZX) for total cholesterol, low-density lipoprotein cholesterol, uric acid, and
      albumin were significantly different (p < 0.05-0.01), showing the result of
      genetic control, because their heritabilities were very high at 0.75-1.0, 0.77
      1.0, 0.96-1.0, and 0.48-0.82, respectively. This study disclosed that the serum
      lipids of children in Taipei, Taiwan were significantly correlated with that of
      parents, which may be attributed to the result of genetic control.

PMID- 10910620
TI  - Thyroid function in the sick very low-birth-weight infants.
AB  - This study was undertaken to determine postnatal changes in thyroid function in
      very low-birth-weight (VLBW) infants. A total of one-hundred VLBW infants
      participated. Serial examination of serum levels of thyroxine (T4), free T4,
      triiodothyronine (T3), and thyroid-stimulating hormone (TSH) was performed in the
      neonatal period. A total of eighty-nine infants survived to discharge, while
      eleven died during hospitalization. Transient hypothyroxinemia was found in forty
      one (46.1 percent) of the survivors. One of the surviving infants had primary
      hypothyroidism. His data was excluded from the analysis. In the other eighty
      eight surviving infants, TSH levels were within normal limits throughout the six
      week study period. T4 and free T4 values decreased after the first day of life,
      reaching a nadir at one week of age, followed by progressive increases. The mean
      cord blood T3 level was very low; the serum T3 value increased progressively in
      the postnatal period. We found a correlation between low T4 and free T4 values
      and mortality and neonatal illness. Hypothyroxinemia was associated with critical
      illness. In conclusion, the postnatal changes in thyroid function in VLBW infants
      were characteristic, with transient hypothyroxinemia being common in these
      infants. Further investigation of the relationship between thyroid function,
      death, neonatal illness, and developmental outcome is warranted.

PMID- 10910621
TI  - Autoimmune manifestations in patients with primary immunodeficiency.
AB  - Primary immunodeficiency comprises a heterogeneous group of disorders. Autoimmune
      and/or rheumatic manifestations are not uncommon in these patients. It may be the
      first and/or sole sign before the underlying disease is established. This study
      focuses on the children of primary immunodeficiency with autoimmune disease to
      survey the clinical and laboratory finding retrospectively. From January 1985 to
      June 1998, ten patients (M:F = 9:1) of primary immunodeficiency with at least one
      well defined autoimmune disease were identified. The underlying immunodeficiency
      included three with Bruton's disease, three with common variable
      immunodeficiency, one with hyper-IgM, one with primary CD4 T-cell deficiency and
      two with Wiskott-Aldrich syndrome. The autoimmune manifestations include
      arthritis in six, ulcerative colitis in one, and autoimmune hemolytic anemia in
      three children. The major treatment was steroid and non-steroid anti-inflammatory
      drug. Infection could be controlled with antibiotics and intravenous
      immunoglobulin in all save one. The morbidity among these patients included
      bronchiectasis with pulmonary hypertension in three, joint stiffness, short
      stature, and delayed puberty in two. In conclusion, autoimmune diseases are
      frequently seen in patients with primary immunodeficiency. It could be the first
      and/or sole sign of disease. The possibility of immunodeficiency should be kept
      in mind when evaluating patients with autoimmune diseases.

PMID- 10910622
TI  - Cardiovascular function in young patients with type 1 diabetes mellitus.
AB  - Echocardiographic assessment of cardiovascular function was performed in 47 type
      1 diabetic patients and 30 healthy control subjects of comparable age, height,
      weight, and heart rate. Indexed left ventricular mass, stroke volume, cardiac
      output, cardiac index, shortening fraction, indexed diastolic dimension, and
      indexed diastolic volume were calculated and compared between patient and control
      groups. Left ventricular mass and performance were slightly elevated in type 1
      diabetic patients compared with 30 healthy control individuals. However, only
      cardiac output had borderline statistical significance (p = 0.06). The reason
      might be short duration (mean, 4.02 +/- 4.07 years) of diabetes in our patients
      group. In 18 of 47 patients the duration of type 1 diabetes was even less than
      two years. Relation of left ventricular mass to independent variables showed
      that, left ventricular mass was significantly correlated with stroke volume (p =
      0.008), cardiac index (p = 0.0005), indexed systolic blood pressure (p =
      0.0000199), indexed diastolic blood pressure (p = 0.0000172) and left ventricular
      contractility (p = 0.000273) in diabetic patients. Left ventricular contractility
      was also independently associated in diabetic patients with the indexed systolic
      and diastolic blood pressure (p = 0.0000755 and 0.000678 respectively). Albumin
      excretion, duration of diabetes, glycosylated hemoglobin (HbAlc), serum
      creatinine, and left ventricular preload did not have significant univariate
      correlation with left ventricular contractility.

PMID- 10910624
TI  - Croup syndrome in children: five-year experience.
AB  - To investigate the etiology and clinical features of croup syndrome, clinical
      records of hospitalized children with a diagnosis of croup syndrome were reviewed
      from April 1990 to January 1996. There was a total of 132 children, aged between
      three months and seven years with a mean age of 21.3 +/- 16.8 months. A diagnosis
      of laryngotracheobronchitis was made in 123 (93.2 percent) children. Twenty-three
      pathogens were identified in twenty-two of them, including seven parainfluenza
      viruses, five respiratory syncytial viruses, four influenza A viruses, four
      Mycoplasma pneumoniae, and three adenoviruses. Bacterial tracheitis was confirmed
      by bronchoscopic examination in seven cases (5.3 percent). Cultures of the
      respiratory secretions yielded viridans streptococci in six and Staphylococcus
      aureus in one child. Two children (1.5 percent) had spasmodic croup. No case with
      epiglottitis was noted in the present study. A fever lasting for more than three
      days was noted in five (71 percent) children with bacterial tracheitis and thirty
      five (28 percent) children with laryngotracheobronchitis (p = 0.048). Among
      children with laryngotracheobronchitis, an associated diagnosis of pneumonia,
      acute otitis media, or paranasal sinusitis was more frequently observed in those
      with fever > 3 days (40 percent) than those with a shorter duration of fever (17
      percent, p = 0.013). In conclusion, a child with a longer duration of fever and
      more severe manifestations of airway obstruction probably has a bacterial cause
      of croup syndrome or a bacterial complication. Bacterial tracheitis is more
      common than epiglottitis in Taiwan.

PMID- 10910623
TI  - Longitudinal study of serum free thyroxine and thyrotropin levels by
      chemiluminescent immunoassay during infancy.
AB  - From October 1996 to December 1997, ninety normal infants born at full-term were
      enrolled in this study. There were 59 female infants and 31 male infants. Both
      serum free thyroxine and thyrotropin levels were measured by chemiluminescent
      immunoassay in the first week (n = 75), 3 months (n = 66), 6 months (n = 79), and
      12 months (n = 77) of age. Serum free thyroxine levels (ng/dL) (mean +/- standard
      deviation) were 2.2 +/- 0.5, 1.3 +/- 0.2, 1.2 +/- 0.2, 1.0 +/- 0.2 for each age
      group, respectively. Serum thyrotropin levels (mIU/L) (mean +/- standard
      deviation) were 9.7 +/- 6.7, 3.0 +/- 1.6, 2.7 +/- 1.3, 2.5 +/- 1.2 for each age
      group, respectively. There was no significant difference between the levels of
      these two parameters between male and female. The present study provides the
      reference data for the normal range of thyroid function during infancy. Our
      results also show that the serum free T4 and TSH levels tend to decline during
      the first year of life.

PMID- 10910625
TI  - An R248C mutation of FGFR3 leading to thanatophoric dysplasia type I.
AB  - Thanatophoric dysplasia (TD) is the most common form of lethal neonatal dwarfism
      with micromelic shortening of the limbs, macrocephaly, platyspondyly, and reduced
      thoracic cavity. R248C mutation in the extracellular domain of fibrobast growth
      factor receptor 3 (FGFR3) was common in TD type I. Two TD type I patients were
      examined for R248C mutation by use of restriction digestion and direct
      sequencing. The results showed that both patients carried R248C mutation. Because
      of the homogeneity of R248C mutation among different ethnic populations, all TD
      patients should be analysed using this PCR-based method presented in this work.

PMID- 10910626
TI  - Hydrops fetalis with complete heart block secondary to congenital lupus: report
      of one case.
AB  - Neonatal lupus erythematosus is an uncommon syndrome characterized by a
      congenital heart block and/or cutaneous lesion. We report a male newborn with
      neonatal lupus erythematosus presenting with complete heart block, cutaneous
      lesions, and hydrops. Transplacental passage of anti-SSA/Ro and anti-SSB/La
      antibodies were positive. Under the regimens of steroid for maternal systemic
      lupus erythematosus, perinatal anticongestive agents, and postnatal ventricular
      pacing with inotropic therapy, the infant died at the age of two days. The
      prognosis of hydrops fetalis secondary to neonatal lupus with complete heart
      block is usually fatal.

PMID- 10910627
TI  - Sonographic and color Doppler sonographic diagnosis of acute osteomyelitis:
      report of one case.
AB  - Acute osteomyelitis in childhood is uncommon. Early diagnosis is often difficult.
      We present a 7-year-old boy with clinical manifestation of fever and progressive
      left thigh swelling for one week. Sonography of the left thigh showed periosteal
      thickening with subperiosteal abscess around the metaphysis of the left distal
      femur. Tc-99m bone scintigraphy showed increased uptakes at the left distal
      femur. Osteomyelitis was suspected from the examination of ultrasound and bone
      scan examinations. His symptoms were not relieved following systemic antibiotic
      therapy and a follow-up color Doppler sonography showed vascular flows within and
      around the periosteum indicating active inflammation. He finally received
      surgical drainage and the operative findings confirmed the diagnosis of
      osteomyelitis. In conclusion, ultrasound may be a helpful and convenient tool for
      establishing the early diagnosis of pediatric osteomyelitis. Ultrasound and color
      Doppler sonography can be used as clinical parameters to evaluate the disease
      severity and the progression of osteomyelitis in children.

PMID- 10910628
TI  - Neonatal intestinal perforation caused by congenital defect of the small
      intestinal musculature: report of one case.
AB  - Congenital defect of the small intestinal musculature is a rare cause of neonatal
      spontaneous intestinal obstruction or perforation. Its etiology and pathogenesis
      are still controversial. A male infant presented with intestinal obstruction at
      two days of age and rapidly progressed to perforation and septic shock. He died
      at seven days of age. Autopsy finding revealed a perforation hole at twenty-five
      cm proximal to ileocecal valve. Histology examination demonstrates multifocal
      deficiency of the inner circular muscle layer three cm around the perforation
      site. The clinical and histological characteristics are reviewed and discussed.
      We propose that the muscle defect of small intestine, especially ileum, is
      secondary to ischemic injury rather than an embryological malformation.

PMID- 10910629
TI  - Noonan syndrome associated with moyamoya disease: report of one case.
AB  - We report a patient with Noonan syndrome who had repeated transient ischemic
      attacks. Moyamoya was diagnosed from the image study. In addition, flunarizine
      therapy seems to be effective in the prevention of recurrent symptoms and signs.
      The association of Noonan syndrome and Moyamoya has been reported. To the best of
      our knowledge, this is the second case report of an association of the Noonan
      syndrome and Moyamoya. Further study should ensue.

PMID- 10910630
TI  - Cystic neuroblastoma with hepatic metastasis: report of one case.
AB  - Neuroblastoma is the most common infant malignancy, but cystic neuroblastoma is a
      rare presentation of this disease. There were only thirty-one reported cases in
      literature. Here we report another case. A 4-month-old female baby presented with
      a huge abdominal mass which was histologically proved to be a cystic
      neuroblastoma. Her urinary vanillylmandelic acid (VMA) was elevated. The image
      studies, including abdominal sonography, computed tomography, and magnetic
      resonance image, revealed a huge main mass with calcification and septa in the
      abdominal cavity, and multiple metastatic nodules with septation in the liver. A
      three-layer fluid-fluid level was found in the main mass and also in the
      metastatic nodules. No previous report showed a three-layer fluid-fluid level in
      the cystic component of neuroblastoma like the case presented here. It may be
      evidence of easy hemorrhagic character of this tumor.

PMID- 10910631
TI  - X-linked agammaglobulinemia presenting as juvenile chronic arthritis: report of
      one case.
AB  - Bruton agammaglobulinemia (X-linked agammaglobulinemia, XLA), transmitted by X
      linked recessive inheritance, affects only males. Twenty percent of patients with
      XLA may have arthritis. Septic arthritis may occur, but there is also a form of
      arthritis that is similar to rheumatoid arthritis or juvenile chronic arthritis.
      Here we report one case of XLA in a boy with non-erosive chronic right knee
      arthritis. There was no evidence of septic arthritis. Regular intravenous
      gammaglobulin replacement therapy and oral naproxen resulted in dramatic
      improvement in the arthritis. This case illustrates that XLA should be considered
      as a possible underlying cause of juvenile chronic arthritis in males.

PMID- 10910633
TI  - [Molecular studies of genetic diseases].

PMID- 10910635
TI  - [Molecular diagnosis of neoplasms].
AB  - Based on general biological features of cancer cells, different aspects of cancer
      diagnostics are discussed.

PMID- 10910634
TI  - [Mitochondrial diseases--causes and diagnosis].
AB  - Increasing numbers of diseases due to disturbances in mitochondrial DNA (mtDNA)
      are being discovered. Mutations in mtDNA mainly cause malfunctioning of muscle
      and nerve cells. The most common diseases and their molecular diagnosis are
      briefly described.

PMID- 10910636
TI  - [Genetic background of retinoblastoma].
AB  - Retinoblastoma is a malignant tumour of the eye ball, which develops as a result
      of the mutation of both alleles of RB-1 gene. Molecular mechanisms and their
      implications in clinical diagnosis and genetic counselling in retinoblastoma
      families are discussed.

PMID- 10910637
TI  - [Neurofibromatosis type 1 --Recklinghausen's disease; pathogenesis and clinical
      symptoms].
AB  - Neurofibromatosis type 1 (NF1) or von Recklinghausen neurofibromatosis is a
      common autosomal dominant disorder affecting 1 in 3000 individuals. The gene for
      NF1 is localized on chromosome 17q11.2. The gene mutations or the inactivation
      its protein product--neurofibromin are responsible for the manifestation of the
      disease. NF1 demonstrates a wide variability of clinical symptoms classified by
      NIH Consensus Conference in 1987.

PMID- 10910638
TI  - [Neurofibromatosis type 2 (NF2)--classical example of a rare familial cancer
      syndrome].
AB  - Type 2 neurofibromatosis (NF2) is a dominantly inherited disorder characterized
      by a predisposition to multiple tumours of the nervous system. The incidence in
      the Caucasian population is estimated between one in 35,000 and one in 40,000 of
      live births. The NF2 gene was isolated and shown to have mutations in NF2
      patients. It is considered to belong to tumour suppressor gene family. Direct NF2
      gene analysis enables verification of tentative clinical diagnosis and makes
      genetic counselling possible.

PMID- 10910639
TI  - [Mutations causing hereditary hyperphenylalaninemia].
AB  - Mutations in the genes encoding different parts of phenylalanine hydroxylation
      system cause persistent hyperphenylalaninaemia. The most frequent form of
      hyperphenylalaninaemia is caused by mutations in the PAH gene. The most common
      variant result from defect of tetrahydrobiopterin synthase. Mutations in the PAH
      and PTS genes in the Polish population are presented. Genotype--phenotype
      correlations are discussed.

PMID- 10910640
TI  - [Molecular genetics of congenital skeletal dysplasias related to mutations of
      fibroblast growth factor receptors].
AB  - Fibroblast growth factor receptors belong to the family of a membrane bound
      tyrosine kinases, which respond to stimulation by the fibroblast growth factor
      family of cytokines. Signalling through fibroblast growth factor receptors
      regulates proliferation and differentiation of connective tissue cells.
      Disruption of these important processes during morphogenesis results in skeletal
      dysplasias. Mutations of the fibroblast growth factor receptors (1, 2 and 3)
      cause achondroplasia, Crouzon syndrome and Apert syndrome, which are amongst the
      most common congenital dysmorphic syndromes. There exists a correlation between
      the genotype and phenotype in fibroblast growth factor receptors related
      syndromes. This relation can be explained on the basis of molecular pathology of
      the receptor protein. An increased frequency of new mutations and exclusive
      paternal origin of mutated alleles is explained by the role of fibroblast growth
      factor signalling during spermatogenesis. The availability of molecular tests for
      fibroblast growth factor receptors related syndromes should facilitate the
      diagnostic accuracy of these pleiotropic diseases which is independent of
      expression variability.

PMID- 10910641
TI  - [Hyperammonaemia type II as one of the congenital urea cycle defects].
AB  - Ornithine transcarbamylase (OTC) deficiency (hyperamonaemia type II; MIM 311250)
      is an X-linked disease inherited by a partially dominant trait. Clinical
      manifestations are more severe in hemizygous males than in heterozygous females.
      To date about 160 different mutations and 10 polymorphisms have been identified
      in the OTC gene. The mutations are mostly point mutations and are equally
      distributed within the gene. The majority of the OTC gene mutations occurred in
      the paternal germ cells. Treatment of the patients requires restriction of
      dietary protein intake and activation of other pathways of waste nitrogen.
      Recently, a study of gene therapy has been started. It consists of the transfer
      of cloned ornithine transcarbamylase sequence into cultured cells and animals.

PMID- 10910642
TI  - [Molecular aspects of familial hypophosphatemic rickets].
AB  - Familial hypophosphataemic rickets (XLH) is an X-linked dominant disorder
      resulting in hypophosphataemia, abnormal regulation of 25-hydroxy vitamin D
      metabolism, elevated activity of alkaline phosphatase, bone deformities and short
      stature. In 1995-97 the sequence of PEX gene responsible for the disease was
      established. The PEX gene spreads 24.3 kb and includes 22 small exons coding a
      protein belonging to a neutral endopeptidase family. Function of the protein is
      not known yet. Mutation analysis in patients from North America, Africa and
      Europe (including Poland) revealed the presence of many different types of the
      PEX gene mutations. Identified deletions, insertions and substitution are
      supposed to change the structure of the PEX protein. Active form of vitamin D3, 1
      alpha-hydroxylase and phosphate supplementation are now the recommended treatment
      of XLH patients. Further research is necessary to understand the role of the PEX
      protein in the pathogenesis of hypophosphatamic rickets.

PMID- 10910643
TI  - [Chronic granulomatous disease].
AB  - Chronic granulomatous disease (CGD) is characterized by severe, protracted and
      often fatal infections, which results from a failure of the NADPH oxidase enzyme
      system in the patient's phagocytes to produce reactive oxygen species (ROS). The
      NADPH oxidase enzyme is a system composed of a number of interacting cytosol and
      membrane components. The absence of any of the components causes failure of the
      system. Mutations in the genes coding various parts of the oxidase system cause
      CGD.

PMID- 10910644
TI  - [Juvenile form of Huntington's disease--diagnostic problems].
AB  - Variability of clinical manifestation is an important feature of Huntington's
      disease (HD). It is due to the high instability of CAG sequences within a coding
      region of IT15 gene. We present five pedigrees in which apart from the adult form
      of HD the juvenile form of the disease affected some of the patients--as a result
      of genetic anticipation. Molecular analysis confirmed the well known fact that
      anticipation, which manifests itself by earlier onset of the disease in the
      subsequent generations, is strongly correlated with the degree of amplification
      of (CAG)n repeats in IT15 gene. An interesting feature of the presented data is
      the fact, that expansion of CAG repeats occurred not only at the paternal but
      also at the maternal transmission of the mutation. Some children in the presented
      HD pedigrees presented other neurological disturbances which could be suspected
      of HD; a molecular analysis revealing normal number of CAG repeats, enabled us to
      avoid misdiagnosis. The presented data provide evidence that clinical diagnosis
      of HD, particularly in cases with not very characteristic clinical picture--is
      not possible without DNA analysis--even in the families undoubtfully affected
      with the disease.

PMID- 10910645
TI  - [Germline mosaicism in a family with Duchenne muscular dystrophy].
AB  - In families with Duchenne/Becker muscular dystrophy, DNA analysis allows direct
      detection of the sex-linked dystrophy gene mutation. The detection of two alleles
      (heterozygous) in the region of a deletion in an affected son, excludes the
      mother having the same deletion. However, it is known that in isolated cases of
      this disease there is a risk of mosaicism, resulting in genetically different
      cell lines in the same or different tissues. Because of this consideration, in a
      subsequent pregnancy, prenatal diagnosis was performed on the mother, who was
      previously excluded from carrying the deletion based on DNA analysis of blood
      leukocytes. The examination showed the sex of the foetus to be male, and notably,
      a deletion identical to that in the ill boy was detected. This indicates that the
      patient has a germ cell deletion (germline mosaicism).

PMID- 10910646
TI  - [Molecular study of bone marrow chimerism and expression of EVI-1 gene as
      manifestations of minimal residual disease after bone marrow transplantation
      (BMT)].
AB  - Leukaemias are the most frequent tumour diseases in children. Bone marrow
      transplantation (BMT) is the most effective therapy for many patients with
      leukaemia. Highly polymorphic microsatellite markers provide useful genetic
      markers for detection of complete or mixed chimerism in patients after (BMT).
      Chimerism can be monitored successfully using several polymerase chain reaction
      (PCR) techniques and cytogenetic analysis, especially fluorescent in situ
      hybridization (FISH). It is still unclear whether individuals with mixed
      chimerism after bone marrow transplantation have an increased risk of developing
      leukaemic relapse or graft rejection. EVI-1 gene was mapped in human chromosome
      3q26. It encodes zinc finger, DNA binding protein detected only in the nucleus.
      The EVI-1 function is unknown. It is not expressed in normal human haematopoietic
      cells, but is expressed in leukaemias especially with 3q26 abnormalities.
      Expression of the EVI-1 may play a significant role in pathogenesis of human
      leukaemias. Molecular study of chimerism and expression of EVI-1 gene may be
      useful for monitoring residual disease after bone marrow transplantation.

PMID- 10910647
TI  - [Molecular diagnosis of inherited disease].
AB  - The ability to detect mutations in nucleic acids sequence is of fundamental
      importance in medical molecular genetics. The aim is to link mutations of
      identified genes to particular disease phenotypes and to facilitate rapid,
      molecular diagnosis. There are numerous techniques described for screening
      unknown mutations, and for diagnosing those which have been identified
      previously. Each method offers different advantages and has its own limitations.

PMID- 10910648
TI  - [Use of polymerase chain reaction for pediatric diagnosis].
AB  - Basic principles of main molecular biology techniques: polymerase chain reaction
      (PCR) and its variants; asymmetric PCR, ARMS, nested PCR, multiplex PCR and
      competitive PCR are discussed. Nucleic acids techniques are making increasing
      progress in molecular diagnostics. Sequence analysis of amplified DNA allows
      better identification of the pathogen, detection of mutant genes and more
      accurate prognosis and therapy of certain diseases.

PMID- 10910649
TI  - [Draft of additional protocol to the convention for the protection of human
      rights and dignity regarding applications to biology and medicine on the
      prohibition of cloning humans].

PMID- 10910650
TI  - [Use of rectal diazepam administration for control of epileptic seizures in
      children. A multicenter study].
AB  - The purpose of this multicentre study of an unselected group of 178 children with
      prolonged convulsions or status epilepticus was to evaluate the effects of rectal
      administration of Diazepam by means of a rectal appliance. We found that diazepam
      is effective against seizures in 98% of cases, has a rapid onset of action and is
      safe. We recommend this form of treatment at all levels of medical care and also
      for use by parents or other care givers.

PMID- 10910651
TI  - [The value of the head-up tilt table test for with unexplained syncope in
      children and young adolescents].
AB  - Syncope occurs in about 15% of children and young adolescents. The diagnosis of
      syncope of unknown origin is frequently difficult. In 1986, Kenny et al.
      introduced the Head-up Tilt Table Test (HUT), which enables to reproduce syncope.
      The aim of the study was to evaluate HUT in diagnosis of syncope in children and
      young adolescents. Ninety five children and young adolescents (57 females, 38
      males, age range 7-18 years) with recurrent syncope of unexplained etiology were
      referred for HUT. The study group was divided into two subgroups: A--with history
      consistent with vasovagal syncope (VVS) and B--with non-characteristic symptoms
      for VVS. HUT was performed according to the Westminster protocol. The patient was
      tilted at 60 degree for 45 min. or until syncope occurred. Positive response to
      HUT was 36%. Negative outcome occurred in 59%. Non-diagnostic HUT was observed in
      5%. The vasodepressive type of VVS was recognised in 35%, cardioinhibitory in 12%
      and mixed in 53%. In group A positive response of HUT occurred in 65% of pts.,
      negative in 31%. In group B positive HUT was observed in 4% of pts. and negative
      in 89%. CONCLUSIONS: 1. In children and young adolescents head-up tilt test is a
      very useful diagnostic method. 2. In patients referred for the head-up tilt test
      the history of syncope should be taken into consideration.

PMID- 10910653
TI  - [Influence of immediate newborn care on infant adaptation to the environment].
AB  - The indicators of newborns' adaptation during 75 min after birth were compared in
      three randomised groups of full-term newborns: skin-to-skin contact (group I),
      swaddled newborns beside the mother (group II), swaddled and separated from the
      mother (group III). The changes in skin temperature, blood glucose, pH, heart
      rate, respiration rate and crying time were studied. All the above
      characteristics but pH were significantly the most favourable for infants in the
      skin-to-skin group. The analysis of individual trends of changes in skin
      temperature indicated that for all but two newborns not separated from the mother
      (skin-to-skin or lying besides) the temperature was growing during the
      observation period, whereas in the separated group, six newborns (27%) had
      unstable not growing temperature. The mean level of blood glucose was the highest
      in skin-to-skin group (60.1 mg/dl), lower in group of swaddled and lying beside
      mother (52.5 mg/dl) and the lowest (49.6 mg/dl) in the separated group. The mean
      duration of crying time in the skin-to-skin contact was a little shorter than in
      the group of newborns lying besides the mother and more than three times shorter
      than in the separated group. The observed number of episodes of crying were 7, 17
      and 38 in the three groups respectively. All results indicated that skin-to-skin
      contact is optimal for newborns', adaptation after birth especially as a
      protection against hypothermia and hypoglycaemia.

PMID- 10910652
TI  - [Breastfeeding and HIV infection].
AB  - In developing countries, the benefits of breastfeeding in relation to the child's
      survival outnumber the risk of transmitting HIV via the mother's milk. In these
      countries different actions are undertaken to reduce the risk of vertical
      transmission during breastfeeding. On the contrary, in the developed countries
      HIV positive mothers are strongly recommended to avoid breastfeeding due to a
      high and well documented risk of transmitting the virus to a child this way. The
      following three important questions need to be addressed if we are to apply
      different interventions aimed at reducing the risk of postnatal vertical
      transmission of HIV: what is the rate of HIV vertical transmission through
      breastfeeding? When exactly can this transmission take place? What are the risk
      factors for HIV transmission? Although these questions are not easily answered
      and we only have estimates of the transmission rates, certain facts should be
      noted: the rate of transmission through breastfeeding is definitely high, primary
      HIV infection in a breastfeeding mother (postnatal infection) is related to the
      significantly increased risk of HIV transmission to the child, the risk of HIV
      transmission is almost double in the case of children breastfed for longer than
      15 months.

PMID- 10910655
TI  - [Nocturnal enuresis in children. II--Diagnosis and treatment of nocturnal
      enuresis].
AB  - The classification of the various types of urination disorders among children as
      well as the latest theories explaining the causes of nocturnal enuresis were
      presented in the first part of the article entitled "Nocturnal Enuresis in
      Children" (in "Medycyna Wieku Rozwojowego" 1998, II, 1 pp. 55-69). The second
      part of this article concentrates on the differential diagnostics of urination
      disorders amongst patients seeking help for nocturnal enuresis. The diagnostic
      model developed by the Urodynamic Unit at the Department of Paediatric Surgery,
      National Research Institute of Mother and Child can be applied in an outpatient
      clinic. Hospitalization of the patient is not necessary to carry out the study,
      meaning that the child is spared any additional stress. Currently applied methods
      for treating nocturnal enuresis by non-pharmacological methods are also discussed
      in this text.

PMID- 10910654
TI  - [Apoptosis and hepatic cell proliferation in autoimmune hepatitis and chronic
      viral hepatitis C in children: analysis of APO-1/Fas (CD95), bcl-2 and Ki67
      expression].
AB  - Hepatocyte damage in autoimmune hepatitis (AIH) and chronic viral hepatitis C
      (CVH) is attributed to an immune response. We analysed liver biopsy specimens
      from 4 children with AIH type I, 3 children with AIH type II and 2 children with
      CVH, using ApopDetek in situ hybridisation method and Mabs anti CD95, Ki67, bcl-2
      by means of APAAP technique. The histological appearance of apoptotic bodies in
      both conditions was similar. The proliferation activity of the hepatocytes was
      elevated in cases of CVH and less extensive in AIH. Immunohistochemical analysis
      suggested that the liver damage in AIH and CVH could be mediated by CD95 system
      as a mechanism of T-cell mediated cytotoxicity.

PMID- 10910656
TI  - [Evaluation of treatment and preventive care for recurrent urolithiasis in
      children].
AB  - Among 425 children with urolithiasis treated in the Paediatric Clinical
      Department of the National Research Institute of Mother and Child in Warsaw
      between 1976-1997, 50 of them i.e. 11.7% (26 boys and 24 girls) had recurrent
      urolithiasis. Patients' age was from 10 months to 16 years and 5 months. The
      number of recurrences of uroliothiasis before treatment in the Institute was from
      1 to 8. Most of the children had numerous surgical operations, some of them
      excreted stones spontaneously. The etiology was determined in all cases. A
      metabolic cause of urolithiasis was found in 34 cases, i.e. 68% of the analysed
      group. They were as follows: idiopathic hypercalcuria--24 cases, uric acid
      urolithiasis--5 cases, cystynuria--4 cases, and incomplete distal renal tubular
      acidosis--1 case. Other reasons for urolithiasis were: infection--7 cases,
      idiopathic urolithiasis--8 cases, ren spongiosum--1 case. Prevention of
      recurrences depending on the etiology was successful. In 45 cases no recurrences
      were found. Recurrent urolithiasis was observed in 4 cases of cystynuria and in
      one case of incomplete tubular acidosis. The observation period was from 3-19
      years.

PMID- 10910658
TI  - [Microbiological evaluation of the vagina in women being screened for
      inflammatory and precancerous conditions of female genitalia].
AB  - The aim of this work was to study the microbiology of vaginal secretion in 3665
      (19 to 72 year old) women investigated in the screening programme for
      inflammatory and malignant diseases. Microbiological examinations of the vaginal
      contents were carried out using direct preparations (Miller and Gram methods) and
      different media for cultures. Normal biocenosis (I and II grade of cleanliness)
      of the vagina was observed in 40.74% investigated patients. Abnormal biocenosis
      was classified as early, advanced and chronic state infections. In our study we
      present data on isolated strains of saprophytic organisms and pathogens including
      yeasts and Trichomonas vaginalis in early and chronic infections. There were
      homogeneous and mixed infections. The role of the physiological Lactobacillus
      species inhibiting development of pathogenic flora is suggestive of beneficial
      influence on the vaginal environment. Candidiasis of the vagina was identified in
      11.35% examined women. High percentage Candida growth was found together with
      Lactobacillus vaginalis. It is noteworthy that trichomoniasis was less frequent
      compared to our previous reports. Totally we were able to isolate 2597 strains of
      bacteria. Bacteria type of abnormal biocenosis was found in 46.82%. The data from
      this study indicated that microbiological pictures (stained acc. to both Miller
      and Gram methods) are still of importance for the evaluation of vaginal contents.
      The second significant factor in microbiology of human vagina is the role of
      culture. This role of cultures for microbiologic studies of vaginal contents is
      beyond any doubt.

PMID- 10910657
TI  - [Flow cytometry, basic principles and applications--with special reference to
      pediatrics].
AB  - Flow cytometry in clinical applications and research is the result of knowledge
      and techniques concerning cyto and fluorochemistry, laser technology, monoclonal
      antibodies and computer processing. Flow cytometry can assess multiple physical
      and biological cell properties, in a relatively short period of time. It is
      specially important, that specimens can concern different types of material:
      fresh solid tissue, embedded in paraffin, blood, bone marrow, body fluids. Under
      optimal conditions (standarization of method and quality control) precise and
      objective analysis of a large number of cells is provided. An experienced team
      and cooperation with clinicians and pathologists are indispensable for correct
      clinical interpretation of flow cytometry data. The aim of this study mainly
      concerns: general principles of flow cytometry operation, clinical applications-
      especially in paediatrics. It is also an encouragement to use this valuable and
      modern instrument in clinical and research work.

PMID- 10910659
TI  - [Preliminary evaluation of health behavior in obese students from a selected
      group of Warsaw adolescents].
AB  - The aim of this study was to assess health behaviour in obese pupils aged 11-17
      years in one of the districts in Warsaw. Self-assessment about own health,
      appearance and possibilities was also studied. Questionnaire studies were carried
      out in pupils with obesity and in a control group of pupils, with normal body
      weight. We found the biggest deficiency of health promoting behaviour in the
      field of physical activity and dietary habits. Differences between the two groups
      of pupils were statistically significant. Significant differences were also found
      in self-assessment concerning physical fitness and appearance. We did not find
      any differences between obese and non-obese pupils in health risk behaviour:
      alcohol drinking, tobacco smoking, frequency of injuries and in psychosocial
      indicators.

PMID- 10910660
TI  - [Test questions in adolescent medicine for self-learning and self-evaluation. VI.
      Problems in obstetric and gynecology].

PMID- 10910661
TI  - [Monitoring high dose methotrexate therapy (HD MTX) in children with osteosarcoma
      and computer simulation using a pharmacokinetic model].
AB  - The pharmacokinetics of methotrexate (MTX) was studied in 15 children with
      osteosarcoma, treated (54 courses) with high-dose methotrexate (8, 10 i 12 g/m2;
      4 h i.v. infusion). Pharmacokinetic analysis was performed by standard non
      compartmental methods and using two-compartment nonlinear model with coexistence
      of additional, parallel linear route of elimination from central compartment. The
      model was used for computer simulation and prognosis of the serum-level curve
      course depending on the simulated dosage, enhanced diuresis and simulated kidney
      or liver insufficiency during the dose individualization. The usage of the
      pharmacokinetic model for computer simulations may improve understanding of the
      MTX kinetics and can optimise dosage regimens for the next cycles of
      chemotherapy.

PMID- 10910662
TI  - [Cleft lip and palate--surgical treatment. Personal and other authors' opinions].
AB  - The author describes and motivates her own strategy in the surgical treatment of
      the cleft lip and palate in children. She also presents a short historical review
      of the opinions and the motives of the timing and the modes of surgical treatment
      of this congenital malformation.

PMID- 10910663
TI  - [Cleft lip and palate--problematic cleft speech].
AB  - The early restoration of facial and palatal morphology in patients with cleft of
      lip and/or palate provides the anatomical base for good speech outcome. The
      author gives the up todate overview of the main problems concerning cleft speech,
      such as velopalatal insufficiency and typical articulation errors. The article
      describes the modern methods for the evaluation of VPI and current trends in
      treatment modalities for VPI.

PMID- 10910664
TI  - [Function of the eustachian tube in patients with cleft lip and/or palate].
AB  - This study examines eustachian tube function in 180 children with clefts of the
      palate or lip and palate. The results indicate that before palatoplasty
      dysfunction of eustachian tube is universal. Recovery of eustachian tube function
      depends on type of cleft palate.

PMID- 10910665
TI  - [Selection of patient age for evaluation of treatment results in cleft lip and
      palate].
AB  - The results of the complex treatment of 125 patients with unilateral and
      bilateral lip and palate cleft, aged 3-5, 10-12 and 14-18 years, were evaluated
      by analysis of medical documentation. The study showed that the results of lip,
      vestibule and palate reconstruction and speech can be evaluated already at 12
      years of age. However, final esthetic and functional assessment of the nose and
      maxillo-occlusional conditions is indicated after 14 years of age, best between
      18-20 years.

PMID- 10910666
TI  - [Assessment of long-term results in cleft lip and palate].
AB  - The study concerned 230 patients (175 UCLP and 55 BCLP) aged 14-20, who had been
      treated in the years 1972-82 in accordance with the Centre for Congenital Defects
      programme, at the Department of Plastic Surgery, Medical University of Lodz. The
      follow-up comprised: aesthetic and functional assessment of the lip, upper
      vestibule and nose as well as evaluation of occlusion and speech abilities
      (intelligibility, articulation, nasality). The assessment of lip and vestibule
      gave good and acceptable results in 97% of UCLP patients and in 89% of BCLP. The
      external nose appeared aesthetically and functionally good in 67% of UCLP and in
      94% of BCLP. The defects of occlusion, mainly various forms of cross-bite, were
      found in 48% of UCLP, who had undergone orthodontic treatment. The maxillo
      occlusal defects with no prior orthodontics were found in 63% of UCLP. Alike the
      defects of occlusion in untreated BCLP were most frequent. The intelligibility
      and articulation of speech were significantly better in patients who had
      undertaken the postoperational speech therapy (95%:75%). The assessment in
      general presented better results in UCLP patients, who had been submitted not
      only to surgery but also took up orthodontic treatment and speech therapy.

PMID- 10910667
TI  - [Molecular analysis in Prader-Willi syndrome diagnosis].
AB  - Prader-Willi syndrome is a rare neurogenetic disorder, which is evidence of
      genomic imprinting in undercentromeric region of chromosome 15. Defects of the
      SNRPN gene are the main cause of the syndrome. PWS is an incurable disorder.
      Nevertheless a diagnosis based on DNA analysis is possible. Molecular diagnostic
      research includes DNA methylation analysis in the 15q11-q13 region, the gene
      dosage analysis of the SNRPN gene and the microsatellite polymorphism analysis.
      The result of DNA analysis is the base of verification of the clinical diagnosis.
      It also enables to determine the type of molecular defect, from which a genetic
      risk is depended and what is the base of genetic counselling.

PMID- 10910668
TI  - [Biochemical markers of bone turnover and their use].
AB  - Although the clinician's ability to diagnose and monitor bone disease has
      improved in the past decade, there is still a need for more specific methods of
      assessing disturbances in bone metabolism. This article presents a review of
      biochemical bone markers and their practical applications in various disease
      states. Bone resorption and formation markers are considered to be useful in
      diagnosis and anticancer treatment of primary osseous tumours and metastatic bone
      diseases. However, better understanding of cellular and molecular events in the
      different phases of remodeling seems to be necessary to develop more adequate
      clinical diagnostic procedures and treatment for bone diseases.

PMID- 10910669
TI  - [Histopathologic differentiation of tumors derived from neuroblastic cells in
      children depending on age].
AB  - The histopathology of 224 tumours of neuroblastic origin was analysed in relation
      to the age of patients. Maturing neuroblastomas (NBS) dominated in infants, where
      as in the most numerous group of children 1-5 years of age, prevalence of
      neuroblastomas without any signs of maturation was noted. In children over 5
      years of age a high incidence of tumours with evident maturation was noted
      (ganglioneuroblastomas and ganglioneuromas). The prevalence of maturing
      neuroblastomas in infants correlate well with an advantageous clinical course of
      neuroblastomas at this age.

PMID- 10910671
TI  - [Test questions from developmental medicine for self-learning and self
      evaluation].

PMID- 10910670
TI  - [Standard parenteral solutions for children up to 3 years of age].
AB  - Standard parenteral solutions for children up to 3 years of age and body weight 3
      15 kg are presented and mixing procedure under laminar flow is described.

PMID- 10910672
TI  - [Anti-tobacco education programs for children and youth at different stages of
      schooling].
AB  - Anti-tobacco education programmes for children and youth, developed at the
      National Research Institute of Mother and Child, are presented. The targets and
      goals of elaboration and implementation of these programmes are discussed. The
      four programmes contribute to a continuum of anti-tobacco education from
      preschool to secondary school. For each programme, the elaborated educational
      objectives, curriculum structure and methodology are presented. Problems related
      to evaluation of health promotion programmes are discussed in relation to the
      requirements of evidence-based medicine. Results of pilot programme
      implementation are presented. The programmes have been accepted by teachers,
      pupils and parents and can be implemented in the reformed education system in
      Poland.

PMID- 10910674
TI  - [The effect of tobacco smoking on the human immune system].
AB  - The influence of tobacco smoking in development of respiratory, cardiovascular
      diseases and impairment of foetal development is well documented. Recent studies
      have shown adverse effects of tobacco smoke on the immune system. Particular
      place of impact of tobacco smoke is BALT (bronchus-associated lymphoid tissue).
      Tobacco smoking increases the inflammatory processes and also has an
      immunosuppressive effect. It is very important in relation to more frequent youth
      and children diseases linked with the immune system. In school education
      programmes to prevent tobacco smoking carried out by the Institute of Mother and
      Child it is also very important to include this aspect.

PMID- 10910675
TI  - [Primary prevention program for neural tube defects in Poland].
AB  - The National Neural Tube Defect Primary Prevention Programme is presented. The
      programme is based on an information and education campaign aimed at showing
      health benefits derived from appropriate level of consumption of folic acid by
      women of reproductive age.

PMID- 10910673
TI  - [Compensatory antioxidant activity in blood of women whose pregnancy is
      complicated by cigarette smoking].
AB  - In pregnancy complicated by the cigarette smoking the risk of oxidative damage
      depends not only on the amount of physiologically enhanced free oxygen species
      but may be affected by intoxication with tobacco smoke radicals. In the presented
      studies oxidative damage was estimated through measurement of lipid peroxidation,
      level of total antioxidant activity and selected antioxidants in plasma and
      erythrocytes of non-smoking and smoking pregnant women. No differences were found
      between those two groups in the level of lipid peroxidation and antioxidant
      activity. Plasma concentration of vitamin A was lower by 15% in smoking than in
      non-smoking women but vitamin E level did not change. In erythrocytes of the
      smoking group, concentration of reduced glutathione was 35% higher than in the
      non-smoking group but activity of glutathione peroxidase and concentration of
      vitamin E were the same. The observed changes indicate that protection of
      erythrocytes against free radicals may be sufficient to prevent lipid
      peroxidation and may manifest local and adaptive response of metabolism for
      tobacco smoking by pregnant women.

PMID- 10910676
TI  - [Evaluation of knowledge, attitudes and practice in healthy women of childbearing
      age concerning prophylactic folic acid--preliminary report].
AB  - Use of folic acid supplements before conception and during the first trimester of
      pregnancy, is associated with a reduced incidence of neural tube defects. The
      Ministry of Health guidelines recommend the use of folic acid supplements by all
      women in childbearing age. The aim of this study was to evaluate knowledge,
      attitudes and behaviour of women in childbearing age with regard to the
      effectiveness of folic acid prophylaxis in neural tube foetal defects. The effect
      of the education al level on knowledge about folic acid supplementation and its
      implementation was also studied. Data were collected by questionnaires
      administered by trained staff in July 1999 in 8 Primary Health Centres in Warsaw
      on a sample of 400 women aged 15-50. Only 52.8% of women reported ever hearing of
      or reading about folic acid, 15% reported that folic acid helped to reduce the
      risk for neural tube defects. The most commonly cited sources of information were
      the woman's general practitioner (43.0%) and magazines (41.7%). Overall, 13% of
      women reported taking multivitamins containing folic acid on a daily basis.
      Failure to take supplements was significantly associated with lower education.
      Educational interventions are required to inform women of the benefit of peri
      conceptional folate supplementation and to increase folate intake among them.

PMID- 10910677
TI  - [Methylene tetrahydrofolate reductase mutations as genetic risk factors for
      neural tube defects (NTF)].
AB  - Folic acid supplementation before conception and during the first trimester of
      pregnancy prevents about 70% of all neural tube defects (NTD). Folic acid is a
      cofactor in the homocysteine metabolism. Its product--S-adenosylmethionine is a
      major methyl donor for reactions taking place in a cell. The 677 C-->T mutation
      in the methylene tetrahydrofolate reductase gene leads to thermolability and
      decreased activity of the enzyme. In the individuals homozygous for that mutation
      hyperhomocystynemia and lowered plasma folate level are observed. Presence of the
      MTHFR 677 C-->T mutation increases the requirements for folic acid, especially at
      the time of rapid foetal growth. Studies showed higher rate of TT homozygotes in
      people with NTD and their parents compared with the control group.
      Hyperhomocystynemia has been associated with higher risk of recurrent
      miscarriages in women. It was also proved that stillbirths are a risk factor
      associated with NTDs. TT homozygosity varies among different country populations,
      from 6% to 16%. An additional risk factor for NTD is MTHFR 1298 A-->C mutation.
      Combined heterozygosity for the 1298 A-->C and 677 C-->T mutations is associated
      with increased homocysteine and lowered plasma folate levels. This genotype is
      more frequent in NTD patients compared with controls. Further investigations in
      the field of genetic aspects of NTD in Poland will be very important for the
      primary prevention of NTD.

PMID- 10910678
TI  - [Evaluation of the usefulness for neonatal mass screening in light of 35 years
      personal experience].
AB  - The results and the significance of neonatal mass-screening programmes for inborn
      errors of metabolism, conducted by the National Research Institute of Mother and
      Child (NRIMC), are discussed. As the first in Poland, in 1964, mass-screening for
      phenylketonuria (PKU) was introduced. The BIA-Guthrie test was used. Other
      Guthrie tests (GBIA) were applied in homocystinuria, tyrosinemia, histidinemia
      and leucinosis (Maple Syrup Urine Disease-MSUD). In the middle of the 60. the
      Beutler and Baluda test was introduced for galactosaemia, as well as the Efron
      urine test in infant screening for different inborn errors of metabolism. In the
      middle of the 70., neonatal mass-screening for cystic fibrosis (CF,
      mucoviscidosis) was started. Meconium tests and the sweat test with ion selective
      chloride electrode were used. Apart from inborn errors of metabolism, we also
      introduced a screening programme for neuroblastoma in which vaniline mandelic
      acid (VMA) in urine was estimated and for congenital hypothyroidism were TSH
      level was assessed. The results of screening are shown in the tables and in the
      figures. In our opinion the best clinical results are obtained with screening for
      congenital hypothyroidism and for PKU, since very early detection and treatment
      in these diseases prevents severe mental retardation. We therefore consider that
      both these screening programmes should be treated as obligatory examinations in
      all neonates. Taking into consideration the fact that there are different types
      of hyperhenylalaninemias, the principles of differential diagnosis are discussed.
      Molecular genetic investigations, carried out in the NRIMC Department of Genetics
      proved to be a very important procedure in the verification of diagnosis of
      different mutations. The authors also discuss the problem of dietary treatment
      duration in PKU. In our opinion the hypophenyloalanine diet regimen in girls,
      should not be discontinued during adolescence, since there is the problem of
      maternal PKU and the possibility of foetal damage. The results of our own
      investigations of maternal PKU are discussed. The significance of mass-screening
      for galactosemia is still under discussion. In our opinion, mass-screening for
      galactosemia is not useful and we have discontinued it. Selective screening has
      been started combined with molecular genetic studies in high risk families. In
      the future, we plan to prepare guidelines on the principles of diagnosis and
      treatment of galactosemia in children and women in the reproductive age. Mass
      screening for cystic fibrosis is also still under discussion. The results of the
      early screening programmes were not satisfactory and the tests were discontinued.
      In 1998, after reorganisation of the whole system, CF screening, using tripsin
      radioimmune assays, was started again. The new screening programme is combined
      with molecular genetic investigation of different mutations. It is still too
      early to assess the importance and success of this CF mass-screening programme.
      We decided to discontinue the screening for homocystinuria, histidinemia,
      tyrosinemia, leucinosis and for neuroblastoma, since these programmes did not
      comply with criteria of mass-screening. In 1997, major reorganisation of
      screening programmes for inborn errors of metabolism, at NRIMC, was undertaken.
      The Guthrie test for PKU was changed to a quantitative colorimetric method. The
      immuno-luminometric method is used for TSH estimation. The whole system is based
      on complete computer control of all the steps of screening, from blood sampling
      on filter paper until the final diagnosis. The advantages of this modern system
      of organisation of the screening programme are discussed.

PMID- 10910679
TI  - [Assessment of the influence of the Chernobyl nuclear disaster on incidence of
      thyroid diseases among children in Poland. Preliminary results].
AB  - It was attempted to assess the incidence of thyroid diseases in Polish children
      born between 1980-1986, who at the time of the Chernobyl nuclear disaster were 0
      6 years old, or whose mothers were in the third trimester of pregnancy. 3071
      children have been examined, 1772 girls and 1299 boys. The following were
      assessed in each child: the health status, the developmental level, the thyroid
      ultrasound examination, and the level of TSH, FT4, antithyroid antibodies ATM and
      ATGL in the blood serum. Disorders in thyroid morphology (abnormal echogenicity)
      have been found in 462 children (15%), almost twice as much in girls than in
      boys. Goiter has been recognized in 4.6% of all children, an abnormal echogenity
      in 5.4% and focal changes in 4.8%. 3.9% of children have been found to have a
      high level of ATM antibodies, and 8.7%--a high level of ATGL antibodies. Among 6
      children, who had thyroidectomy, 2 children have been diagnosed to have ca
      papillary and 4 children--adenoma.

PMID- 10910680
TI  - [Evaluation of the possibility of using the National Cancer Registry for survival
      analysis of children and youth with selected malignancies--leukemias and
      lymphomas during 1990-1995 in Poland].
AB  - There are about 1400 new cases of cancer and almost 600 deaths from cancer a year
      in children and youth aged between 0-19 in Poland. Leukaemias and lymphomas
      comprise 37.8% of the total number of cases and 43.3% of the total number of
      deaths from cancer. The National Cancer Registry is the unique data source of the
      incidence of cancer as well as further health information in particular the fact
      of death. In this research, pioneer attempt of using Registry data to conduct
      survival analysis in children and youth with leukaemias and lymphomas has been
      undertaken. Cox regression and Kaplan-Meier survival curves methods were used.
      Organizational and clinical conclusions have been formulated. Organizational
      conclusions concern mainly the principles of conducting the Registry namely
      introducing of International Classification of Diseases for Oncology (ICD-O) and
      extending the period of observation from 2 to 5 years. The leading clinical
      conclusions are: lack of improvement in prognosis in the 6 years period from 1990
      to 1995 and crucial importance of early diagnosis of oncological disease for
      survival time. Further clinical conclusions concerning the impact of treatment
      cannot be made on the basis of the Registry data.

PMID- 10910682
TI  - [Hansa-East Project open architecture for hospital information systems-
      preliminary report].
AB  - Results of implementation of middleware based hospital information system in the
      National Research Institute of Mother and Child in Warsaw are presented. This was
      objective of the international information technology (IT) Hansa-East Project
      dedicated to promotion of UE standards CEN/TC251 ENV 12967-1 for open
      architecture of hospital information systems. Middleware DHE of the Italian
      company GESI was used. In the paper, the methodology of middleware based hospital
      information system is presented, as well as preliminary evaluation.

PMID- 10910681
TI  - [Evaluation of the possible use of the National Cancer Registry for survival
      analysis of children and youth with selected malignant neoplasms--tumors in 1990
      1995 in Poland].
AB  - This paper is the continuation of previous research described in the article
      "Evaluation of the possibility of using the National Cancer Registry in survival
      analysis of children and youth with selected malignancies-leukaemias and
      lymphomas in 1990-1995 year in Poland" on the basis of the National Cancer
      Registry data concerning tumours. Tumours comprise 62.0% of total number of cases
      and 56.6% of total number of deaths from cancer in children and youth. Modern
      methods of statistical analysis such as Cox regression and Kaplan-Meier survival
      curves method have been used. The conclusion formulated in the previous paper is
      still valid. Despite the fact that the Registry is not designed for survival
      analysis, they are possible and are the basis of many important findings. The
      crucial factor for the value of the Register in the time of advanced statistical
      analysis and computer methods is organisation of the Registry and data quality.
      Organizational and clinical conclusions have been formulated. Organizational
      conclusions concern mainly the principles of conducting the Registry namely
      introducing of International Classification of Diseases for Oncology (ICD-O) and
      extending it from 2 to 5 years the period of observation. The leading clinical
      conclusions are: lack of improvement in prognosis in the 6 years period 1990-1995
      and crucial importance of early diagnosis of oncological disease for survival
      time. Further clinical conclusions concerning the impact of treatment cannot be
      stated on the basis of the Registry data.

PMID- 10910684
TI  - Relaxation-induced dipolar exchange with recoupling-An MAS NMR method for
      determining heteronuclear distances without irradiating the second spin
AB  - A new magic-angle spinning NMR method for distance determination between unlike
      spins, where one of the two spins in question is not irradiated at all, is
      introduced. Relaxation-induced dipolar exchange with recoupling (RIDER)
      experiments can be performed with conventional double-resonance equipment and
      utilize the familiar pi-pulse trains to recouple the heteronuclear dipolar
      interaction under magic-angle spinning conditions. Longitudinal relaxation of the
      passive spin during a delay between two recoupling periods results in a dephasing
      of the heteronuclear coherence and consequently a dephasing of the magnetization
      detected after the second recoupling period. The information about the dipolar
      coupling is obtained by recording normalized dephasing curves in a fashion
      similar to the REDOR experiment. At intermediate mixing times, the dephasing
      curves also depend on the relaxation properties of the passive spin, i.e., on
      single- and double-quantum longitudinal relaxation times for the case of I = 1
      nuclei, and these relaxation times can be estimated with this new method. To a
      good approximation, the experiment does not depend on possible quadrupolar
      interactions of the passive spin, which makes RIDER an attractive method when
      distances to quadrupolar nuclei are to be determined. The new method is
      demonstrated experimentally with (14)N and (2)H as heteronuclei and observation
      of (13)C in natural abundance. Copyright 2000 Academic Press.

PMID- 10910683
TI  - [Organization of school health care during health reform implementation in
      Poland].
AB  - School children and adolescents needs particularly good medical health care
      because of the specific character of this developmental period and the danger due
      to risky behaviours among pupils. The aim of this study was to assess the quality
      prophylactic health care for pupils in the early stage of initiating health care
      reforms. The initiation of the health reform on January 1st 1999 caused a
      deterioration of prophylactic medical health care in pupils. It may also produce
      more health problems among school children and adolescents in the future.

PMID- 10910685
TI  - Initial conditions for carbon-13 MAS NMR 1D exchange involving chemically
      equivalent and inequivalent nuclei
AB  - A major problem in dynamic 1D (13)C MAS NMR concerns the exchange between
      magnetically inequivalent, but chemically equivalent sites, whose signals are not
      resolved in the regular 1D spectrum. This difficulty may be overcome by properly
      preparing the initial nonequilibrium state of the spin system in the exchange
      experiments. In the present paper we discuss the advantages and limitations of
      several such experiments already in use and propose a new sequence, which we term
      SELDOM-ODESSA. Unlike the other 1D-exchange methods, this experiment yields pure
      absorption spectra that can more readily be analyzed quantitatively. The
      experiment is a hybrid comprising a SELDOM sequence, for selective excitation of
      one of the spinning sideband manifolds in the spectrum, followed by the ODESSA
      sequence, which induces alternate polarization in the excited sideband manifold.
      The evolution of the spectrum following this sequence provides information on
      both the exchange between congruent sites belonging to the same group of
      equivalent nuclei, and the exchange between inequivalent sites. Results are
      presented for a tropolone sample specifically enriched in carbon-13 at the
      carbonyl and hydroxyl sites. The dominant exchange mechanism in this sample
      involves spin diffusion. The various spin exchange processes in this sample, in
      the presence and absence of proton decoupling during the mixing time, are
      measured and discussed. Copyright 2000 Academic Press.

PMID- 10910686
TI  - Reducing inhomogeneity artifacts in functional MRI of human brain activation-thin
      sections vs gradient compensation.
AB  - We evaluated two methods for correcting inhomogeneity-induced signal losses in
      magnetic resonance gradient-echo imaging that either use gradient compensation or
      simply acquire thin sections. The strategies were tested in the human brain in
      terms of achievable quality of T2*-weighted images at the level of the
      hippocampus and of functional activation maps of the visual cortex. Experiments
      were performed at 2.0 T and based on single-shot echo-planar imaging at 2. 0 x
      2.0 mm(2) resolution, 4 mm section thickness, and 2.0 s temporal resolution.
      Gradient compensation involved a sequential 16-step variation of the refocusing
      lobe of the slice-selection gradient (TR/TE = 125/53 ms, flip angle 15 degrees ),
      whereas thin sections divided the 4-mm target plane into either four 1-mm or
      eight 0.5-mm interleaved multislice acquisitions (TR/TE = 2000/54 ms, flip angle
      70 degrees ). Both approaches were capable of alleviating the inhomogeneity
      problem for structures in the base of the brain. When compared to standard 4-mm
      EPI, functional mapping in the visual cortex was partially compromised because of
      a lower signal-to-noise ratio of inhomogeneity-corrected images by either method.
      Relative to each other, consistently better results were obtained with the use of
      contiguous thin sections, in particular for a thickness of 1 mm. Multislice
      acquisitions of thin sections require minimal technical adjustments.

PMID- 10910687
TI  - Separation of anisotropy and exchange broadening using (15)N CSA-(15)N-(1)H
      dipole-dipole relaxation cross-correlation experiments.
AB  - Based on the measurement of cross-correlation rates between (15)N CSA and (15)N
      (1)H dipole-dipole relaxation we propose a procedure for separating exchange
      contributions to transverse relaxation rates (R(2) = 1/T(2)) from effects caused
      by anisotropic rotational diffusion of the protein molecule. This approach
      determines the influence of anisotropy and chemical exchange processes
      independently and therefore circumvents difficulties associated with the
      currently standard use of T(1)/T(2) ratios to determine the rotational diffusion
      tensor. We find from computer simulations that, in the presence of even small
      amounts of internal flexibility, fitting T(1)/T(2) ratios tends to underestimate
      the anisotropy of overall tumbling. An additional problem exists when the N-H
      bond vector directions are not distributed homogeneously over the surface of a
      unit sphere, such as in helix bundles or beta-sheets. Such a case was found in
      segment 4 of the gelation factor (ABP 120), an F-actin cross-linking protein, in
      which the diffusion tensor cannot be calculated from T(1)/T(2) ratios. The (15)N
      CSA tensor of the residues for this beta-sheet protein was found to vary even
      within secondary structure elements. The use of a common value for the whole
      protein molecule therefore might be an oversimplification. Using our approach it
      is immediately apparent that no exchange broadening exists for segment 4 although
      strongly reduced T(2) relaxation times for several residues could be mistaken as
      indications for exchange processes.

PMID- 10910688
TI  - NMRLAB-Advanced NMR data processing in matlab
AB  - NMRLAB is a toolbox for NMR data processing in MATLAB (The Mathworks). MATLAB is
      a matrix-oriented high-level programming environment which gives access to fast
      algorithms for a large number of numerical tasks on many common computer
      platforms. To take advantage of fast matrix operations in MATLAB most processing
      commands in NMRLAB have been vectorized. Data processing can be achieved either
      by scripts or by a user-friendly command structure. An interface to WaveLab
      enables spectral denoising employing wavelet transforms. The use of wavelet
      denoising is demonstrated for one- and two-dimensional data. Copyright 2000
      Academic Press.

PMID- 10910689
TI  - Spectral estimation of NMR relaxation
AB  - In this paper, spectral estimation of NMR relaxation is constructed as an
      extension of Fourier Transform (FT) theory as it is practiced in NMR or MRI,
      where multidimensional FT theory is used. nD NMR strives to separate overlapping
      resonances, so the treatment given here deals primarily with monoexponential
      decay. In the domain of real error, it is shown how optimal estimation based on
      prior knowledge can be derived. Assuming small Gaussian error, the estimation
      variance and bias are derived. Minimum bias and minimum variance are shown to be
      contradictory experimental design objectives. The analytical continuation of
      spectral estimation is constructed in an optimal manner. An important property of
      spectral estimation is that it is phase invariant. Hence, hypercomplex data
      storage is unnecessary. It is shown that, under reasonable assumptions, spectral
      estimation is unbiased in the context of complex error and its variance is
      reduced because the modulus of the whole signal is used. Because of phase
      invariance, the labor of phasing and any error due to imperfect phase can be
      avoided. A comparison of spectral estimation with nonlinear least squares (NLS)
      estimation is made analytically and with numerical examples. Compared to
      conventional sampling for NLS estimation, spectral estimation would typically
      provide estimation values of comparable precision in one-quarter to one-tenth of
      the spectrometer time when S/N is high. When S/N is low, the time saved can be
      used for signal averaging at the sampled points to give better precision. NLS
      typically provides one estimate at a time, whereas spectral estimation is
      inherently parallel. The frequency dimensions of conventional nD FT NMR may be
      denoted D(1), D(2), etc. As an extension of nD FT NMR, one can view spectral
      estimation of NMR relaxation as an extension into the zeroth dimension. In nD
      NMR, the information content of a spectrum can be extracted as a set of n-tuples
      (omega(1), ellipsis omega(n)), corresponding to the peak maxima. Spectral
      estimation of NMR relaxation allows this information content to be extended to a
      set of (n + 1)-tuples (lambda, omega(1), ellipsis omega(n)), where lambda is the
      relaxation rate. Copyright 2000 Academic Press.

PMID- 10910690
TI  - Calculation of cross-polarization spectra influenced by slow molecular tumbling
AB  - A numeric algorithm which is suitable for calculating lineshapes of cross
      polarization spectra influenced by isotropic and anisotropic tumbling is
      proposed. It is based on a description of the cross-polarization process using
      single-transition operators combined with rotational diffusion represented by a
      stationary Markov operator. A corresponding Fortran program can be implemented on
      a regular personal computer. The calculations yield spectral lineshapes for
      various mixing times under given cross-polarization conditions which reflect the
      characteristics of molecular motion. Representative results show typical
      transient oscillations on powder spectra, the dependence of the lineshapes on the
      degree of mobility, the effects of sample spinning, the consequence of a given
      deviation from the Hartmann-Hahn condition, and the effect of additional dipolar
      coupling between I spins. The applicability of the algorithm is demonstrated on
      supercooled glycerol as a model system. Copyright 2000 Academic Press.

PMID- 10910691
TI  - A high-resolution (13)C 3D CSA-CSA-CSA correlation experiment by means of magic
      angle turning.
AB  - It is shown in this paper that a previously reported 90 degrees sample flipping
      (13)C 2D CSA-CSA correlation experiment may be carried out alternatively by
      employing constant slow sample rotation about the magic angle axis and by
      synchronizing the read pulse to 13 of the rotor cycle. A high-resolution 3D CSA
      CSA-CSA correlation experiment based on the magic angle turning technique is
      reported in which the conventional 90 degrees 2D CSA-CSA powder pattern for each
      carbon in a system containing a number of inequivalent carbons may be separated
      according to the isotropic chemical shift value. The technique is demonstrated on
      1,2,3-trimethoxybenzene in which all of the overlapping powder patterns that
      cannot be segregated by the 2D CSA-CSA experiment are resolved successfully by
      the 3D CSA-CSA-CSA experiment, including even the two methoxy groups (M(1) and
      M(3)) whose isotropic shifts, confirmed by high-speed MAS, are separated by only
      1 ppm. A difference of 4 ppm in the principal value component (delta(33)) between
      M(1) and M(3) is readily obtained.

PMID- 10910693
TI  - Nuclear magnetic resonance in inhomogeneous magnetic fields
AB  - The response of the spin system has been investigated by numerical simulations in
      the case of a nuclear magnetic resonance (NMR) experiment performed in
      inhomogeneous static and radiofrequency fields. The particular case of the NMR
      MOUSE was considered. The static field and the component of the radiofrequency
      field perpendicular to the static field were evaluated as well as the spatial
      distribution of the maximum NMR signal detected by the surface coil. The NMR
      response to various pulse sequences was evaluated numerically for the case of an
      ensemble of isolated spins (1/2). The behavior of the echo train in Carr-Purcell
      like pulse sequences used for measurements of transverse relaxation and self
      diffusion was simulated and compared with the experiment. The echo train is shown
      to behave qualitatively differently depending on the particular phase schemes
      used in these pulse sequences. Different echo trains are obtained, because of the
      different superposition of Hahn and stimulated echoes forming mixed echoes as a
      result of the spatial distribution of pulse flip angles. The superposition of
      Hahn and stimulated echoes originating from different spatial regions leads to
      distortions of the mixed echoes in intensity, shape, and phase. The volume
      selection produced by Carr-Purcell-like pulse sequences is also investigated for
      the NMR-MOUSE. The developed numerical simulation procedure is useful for
      understanding a variety of experiments performed with the NMR-MOUSE and for
      improving its performance. Copyright 2000 Academic Press.

PMID- 10910692
TI  - Single-quantum coherence filter for strongly coupled spin systems for localized
      (1)H NMR spectroscopy.
AB  - A pulse sequence for localized in vivo (1)H NMR spectroscopy is presented, which
      selectively filters single-quantum coherence built up by strongly coupled spin
      systems. Uncoupled and weakly coupled spin systems do not contribute to the
      signal output. Analytical calculations using a product operator description of
      the strongly coupled AB spin system as well as in vitro tests demonstrate that
      the proposed filter produces a signal output for a strongly coupled AB spin
      system, whereas the resonances of a weakly coupled AX spin system and of
      uncoupled spins are widely suppressed. As a potential application, the detection
      of the strongly coupled AA'BB' spin system of taurine at 1.5 T is discussed.

PMID- 10910694
TI  - MAS as a tool for suppressing dipolar field effects in high-resolution liquid NMR
AB  - We propose high-resolution magic angle spinning as a radical method for the
      suppression of dipolar field effects in liquid NMR. This technique works for any
      sample shape and any spatial distribution of nuclear magnetization. Furthermore,
      it removes any possibility of spectral clustering or instability due to the
      dipolar field. Copyright 2000 Academic Press.

PMID- 10910695
TI  - The virtual NMR spectrometer: a computer program for efficient simulation of NMR
      experiments involving pulsed field gradients.
AB  - This paper presents a software program, the Virtual NMR Spectrometer, for
      computer simulation of multichannel, multidimensional NMR experiments on user
      defined spin systems. The program is capable of reproducing most features of the
      modern NMR experiment, including homo- and heteronuclear pulse sequences, phase
      cycling, pulsed field gradients, and shaped pulses. Two different approaches are
      implemented to simulate the effect of pulsed field gradients on coherence
      selection, an explicit calculation of all coherence transfer pathways, and an
      effective approximate method using integration over multiple positions in the
      sample. The applications of the Virtual NMR Spectrometer are illustrated using
      homonuclear COSY and DQF COSY experiments with gradient selection, heteronuclear
      HSQC, and TROSY. The program uses an intuitive graphical user interface, which
      resembles the appearance and operation of a real spectrometer. A translator is
      used to allow the user to design pulse sequences with the same programming
      language used in the actual experiment on a real spectrometer. The Virtual NMR
      Spectrometer is designed as a useful tool for developing new NMR experiments and
      for tuning and adjusting the experimental setup for existing ones prior to
      running costly NMR experiments, in order to reduce the setup time on a real
      spectrometer. It will also be a useful aid for learning the general principles of
      magnetic resonance and contemporary innovations in NMR pulse sequence design.

PMID- 10910696
TI  - Finite-difference approach for the high-precision analysis of rotating-frame
      diffusion images
AB  - A finite-difference approach has been developed for precisely determining
      diffusion coefficient and T(1) relaxation time in fluid samples analyzed by
      magnetization-grating rotating-frame imaging (MAGROFI) with either a surface coil
      or a toroid cavity detector (TCD). This approach avoids shortcomings of
      phenomenologically based approximations, such as neglect of sample geometries
      with singularities at the confines of the sample volume, and accounts for the
      diffusive edge enhancement observed in fluid imaging. Error limits are discussed.
      The new method has been applied to the determination of the self-diffusion
      coefficient for MAGROFI experiments using TCDs filled with acetone. Copyright
      2000 Academic Press.

PMID- 10910697
TI  - Evidence of red cell alignment in the magnetic field of an NMR spectrometer based
      on the diffusion tensor of water.
AB  - The alignment of human erythrocytes in aqueous suspensions in the magnetic field
      B(0) (called the z-direction) of an NMR spectrometer was shown by calculating the
      diffusion tensor for water in the sample. The diffusion was measured using a
      pulsed-field-gradient spin-echo NMR method. The extent of diffusion anisotropy
      for water was exemplified by the values of the apparent diffusion coefficients
      with erythrocytes of normal shape and volume: for a typical experiment the values
      for the x-, y-, and z-directions were (6.88 +/- 0.17) x 10(-10), (7.07 +/- 0.17)
      x 10(-10), and (10.20 +/- 0.17) x 10(-10) m(2) s(-1), respectively. Cells in hypo
      and hyperosmotic media were also studied and they too showed the anisotropy of
      the apparent diffusion coefficients but the extents were different. A new method
      of data analysis was developed using the Standard Add-On Packages in a
      Mathematica program. The experimental findings support evidence of erythrocyte
      alignment that was previously obtained with a high-field-gradient q-space method.

PMID- 10910699
TI  - 15N chemical shift tensor magnitude and orientation in the molecular frame of
      uracil determined via MAS NMR.
AB  - The potential of heteronuclear MAS NMR spectroscopy for the characterization of
      (15)N chemical shift (CS) tensors in multiply labeled systems has been
      illustrated, in one of the first studies of this type, by a measurement of the
      chemical shift tensor magnitude and orientation in the molecular frame for the
      two (15)N sites of uracil. Employing polycrystalline samples of (15)N(2) and 2
      (13)C, (15)N(2)-labeled uracil, we have measured, via (15)N-(13)C REDOR and (15)N
      (1)H dipolar-shift experiments, the polar and azimuthal angles (&theta;, psi) of
      orientation of the (15)N-(13)C and (15)N-(1)H dipolar vectors in the (15)N CS
      tensor frame. The (&theta;(NC), psi(NC)) angles are determined to be (92 +/- 10
      degrees, 100 +/- 5 degrees ) and (132 +/- 3 degrees, 88 +/- 10 degrees ) for the
      N1 and N3 sites, respectively. Similarly, (&theta;(NH), psi(NH)) are found to be
      (15 +/- 5 degrees, -80 +/- 10 degrees ) and (15 +/- 5 degrees, 90 +/- 10 degrees
      ) for the N1 and N3 sites, respectively. These results obtained based only on MAS
      NMR measurements have been compared with the data reported in the literature.

PMID- 10910698
TI  - Intermolecular dipole-dipole relaxation of (129)Xe dissolved in water.
AB  - Intermolecular (129)Xe-(1)H nuclear Overhauser effects and (129)Xe longitudinal
      relaxation time measurements were used to demonstrate that the dipole-dipole
      coupling is the dominant relaxation mechanism for (129)Xe in water, at room
      temperature. (129)Xe-(1)H cross-relaxation rates were derived to be sigma(XeH)
      approximately 3.2 +/- 0.3 x 10(-3) s(-1), independent of xenon pressure (in the
      range of 1-10 bar) and of the presence of oxygen. Corresponding xenon-proton
      internuclear distances were calculated to be 2.69 +/- 0.12 A. Using the magnitude
      of the dipole-dipole coupling and the spin density ratio between dissolved xenon
      and bulk water, it is estimated that (129)Xe-(1)H spin polarization-induced
      nuclear Overhauser effects would yield little net proton signal enhancement in
      water.

PMID- 10910700
TI  - Imaging of the (1)H NMR second moment with (13)C chemical-shift resolution
AB  - A method of (13)C chemical-shift-resolved (1)H second moment imaging is proposed
      for molecular mobility imaging of heterogeneous materials. For evaluating the
      (1)H second moment, the method relies on the curve fitting procedure using spin
      echo shapes indirectly: The information of (1)H echo shapes is transferred to the
      (13)C signal amplitude through (1)H-(13)C cross polarization and then the curve
      fitting is made using the (13)C signal amplitude. The (13)C signal is detected
      under (1)H dipolar decoupling and magic angle spinning, resulting in the
      incorporation of (13)C chemical-shift resolution. Imaging information is included
      in the (13)C signal by application of phase-encoding gradients. The second moment
      images obtained can reflect the molecular mobility at every molecular site
      separated by (13)C chemical shifts, yielding detailed information on the
      molecular mobility. The method is demonstrated by spatially 1D experiments
      performed on a model sample. Copyright 2000 Academic Press.

PMID- 10910702
TI  - Separation of the ortho and para NMR signals in solid deuterium via DQ filtering
AB  - Double quantum (DQ) filtering is shown to lead to an effective separation of the
      NMR signals from the para (I = 1) and ortho (I = 2) molecules in solid deuterium.
      The separation is achieved by the pulse sequence 90(&phi;)( degrees )-t(pr)
      90(&phi;)( degrees )-t(ev)-90(x)( degrees )-t, where the phase-cycled first two
      pulses create the DQ coherence. Two components are observed after the third
      pulse; the para signal shows the maximum at a short time t while the ortho signal
      reaches the maximum at a longer t. The observed signal can be expressed as (1/2)
      summation operator(I) [F(I)(t(pr) - t) - F(I)(t(pr) + t)], where F(I)(t) is a
      proper fitting function for the free induction signal of the para and ortho
      molecules (with I = 1 or 2, respectively). Numerical fits to experimental data at
      4.2 and 2 K show that this method can be used to determine the ratio
      F(1)(0)/F(2)(0) and thus, because the initial value F(I)(0) is proportional to
      the respective magnetization before the pulse sequence, the ortho and para
      concentrations in solid deuterium. Copyright 2000 Academic Press.

PMID- 10910701
TI  - ENDOR spectroscopic and molecular orbital study of the dynamical properties of
      the side chain in radical anions of ubiquinones Q-1, Q-2, Q-6, and Q-10.
AB  - The dynamics of the side chain of the radical anions of ubiquinones Q-1 (2,3
      dimethoxy-5-methyl-6-[3-methyl-2-butenyl]-1,4-benzoquinone), Q-2, Q-6, and Q-10
      have been investigated using electron nuclear double-resonance (ENDOR)
      spectroscopy. When radicals are produced in the liquid phase, secondary radicals
      are also formed. The EPR spectra of these additional radicals overlap with the
      radical of interest. ENDOR spectroscopy was found to be capable for studying the
      dynamical properties of such conditions. The temperature dependence of the
      isotropic hyperfine coupling constants of the beta- and gamma-protons of the side
      chain was measured. The activation energy of the rotation and other dynamical
      properties of the side chain were calculated assuming that rotation can be
      modeled by the classical two-jump model. The rotation energy barrier for Q-1 was
      also determined by the hybrid Hartree-Fock/density functional method UB3LYP with
      the 6-31G(d) basis set. Calculated results were in good agreement with the
      experimental results. Despite the numerous parameters affecting the ENDOR
      linewidth ENDOR spectroscopy was shown to be a potential method for studying the
      dynamical properties of the mixtures of the radicals. Prominent forbidden
      transitions appear in the ENDOR spectra when alkali ions are present in the
      sample. From these transitions measured ENDOR-induced EPR spectra showed an
      additional doublet and phase transition in electron Zeeman frequency.

PMID- 10910703
TI  - Sample restriction using magnetic field gradients in high-resolution solid-state
      NMR
AB  - Many solid-state NMR experiments are sensitive to inhomogeneity in the
      radiofrequency field. We propose a method to restrict the sample volume, in magic
      angle spinning experiments, using a static magnetic field gradient and a
      selective pulse. The position of the gradient is calculated for our experimental
      configuration and we have simulated the effects of selective pulses to determine
      the excited volume. The resulting sequences are applied to a sample of sodium
      acetate using frequency-switched Lee-Goldburg proton-proton homonuclear dipolar
      decoupling. A gain of a factor of 2 on the carbon resolution is experimentally
      observed. Copyright 2000 Academic Press.

PMID- 10910704
TI  - Double-quantum filtration under rotational-resonance conditions: numerical
      simulations and experimental results
AB  - The dependence of the performance of a recently introduced pulse sequence to
      achieve double-quantum excitation under the n = 1 rotational-resonance condition
      (T. Karlsson, M. Eden, H. Luthman, and M. H. Levitt, 2000, J. Magn. Reson. 145,
      95-107) on different spin-system properties is investigated by means of numerical
      simulations and (13)C MAS NMR experiments. For spin systems where chemical
      shielding anisotropies amount to only an insignificant fraction of the isotropic
      chemical shielding difference, high efficiencies are found for large and small
      dipolar coupling interactions. In the presence of significant chemical shielding
      anisotropies the overall efficiencies decrease and become strongly dependent on
      the duration of the excitation period. It is demonstrated that those spin-system
      parameters which are sensitively encoded in the lineshapes of a conventional n =
      1 rotational-resonance spectrum are similarly sensitively encoded in the
      corresponding rotational-resonance double-quantum-filtered lineshapes and may be
      quantitatively recovered by iterative lineshape-fitting approaches. In certain
      favorable circumstances, the in-built selectivity of the rotational-resonance
      double-quantum-filtration approach permits successful application of the
      experiment on spin systems with more than two spins. Copyright 2000 Academic
      Press.

PMID- 10910706
TI  - A dip in powder deuterium NMR lineshapes
AB  - An analysis of powder (2)H NMR lineshapes based on the Redfield theory reveal an
      interesting dip at the center of the powder spectra, that is, at the magic angle
      beta = 54.7. This extra feature, which has completely been ignored in the
      literature, has interesting dynamic implications. From its presence or absence it
      is possible to tell whether the dominant dynamic process causing relaxation is
      fast or slow relative to the inverse of the Larmor frequency, 1/omega(0). The
      angle-dependent lineshape function is derived in closed form and the powder
      spectra are displayed for two typical cases. Copyright 2000 Academic Press.

PMID- 10910705
TI  - ESEEM measurements with time-resolved detection of the entire ESE signal shape.
AB  - In this work we discuss the extension of electron spin-echo envelope modulation
      (ESEEM) measurements to the additional time dimension, the spin-echo coordinate.
      The time-resolved acquisition of the entire spin-echo signal shape retains
      information on the dependence of the ESEEM amplitude on the position within the
      ESE signal. Therefore, not only can such acquisition be completely substituted
      for the boxcar integration in ESEEM measurements, but it can also improve the
      performance of the ESEEM experiments in terms of obtaining correct modulation
      amplitudes and a better signal/noise ratio. Implementing such an acquisition in
      pulse-adjustable ESEEM measurements transforms these techniques into routine and
      convenient experiments used to increase the modulation amplitude.

PMID- 10910707
TI  - Polarization transfer in lipid membranes.
AB  - Polarization transfer is a key experiment for the detection of insensitive nuclei
      by NMR. Transfer in liquids is often achieved through J-coupling using the INEPT
      experiment, while in solids the dipolar coupling is used with cross polarization.
      Liquid crystals, including lipid membranes, are intermediate cases between solids
      and liquids. In the present article, we compare several transfer methods for
      lipid membranes spinning at the magic angle. It is shown that the most commonly
      used cross polarization technique is, in most cases, advantageously replaced by
      refocused INEPT or even by the NOE enhancement experiment, a method that is not
      normally used in that context. In principle, these enhancement techniques could
      be applied to other systems, including biological tissues and, more generally,
      soft matter systems that are neither solid nor liquid by NMR standards.

PMID- 10910708
TI  - Structurally conserved soluble acid phosphatases are synthesized and released by
      Leishmania major promastigotes.
AB  - Previously it was reported that promastigotes of virtually all pathogenic
      Leishmania species, except Leishmania major, release a structurally conserved
      soluble acid phosphatase (AcP) activity during their growth in vitro (P. S. Doyle
      and D. M. Dwyer, Exp. Parasitol. 77, 435-444 1993). In the current study we used
      a highly sensitive fluorogenic detection method to demonstrate that soluble AcPs
      were in fact produced by promastigotes of several different strains of L. major.
      These L. major AcP activities were readily immunoprecipitated with a rabbit
      antibody previously generated against the L. donovani AcP. Results of metabolic
      labeling and immunoprecipitations demonstrated that AcPs produced by the L.
      majors strains examined had an apparent molecular mass of approximately 77 kDa.
      Results of Southern hybridization analysis with an L. donovani AcP gene probe
      showed that the AcP gene loci were conserved in the L. major strains examined.
      Taken together, these results indicate that the AcP enzyme has been structurally
      and functionally conserved throughout the evolution of pathogenic species of
      Leishmania. Such conservation suggests that the AcPs play a functional role in
      the growth and survival of this group of important human pathogens.

PMID- 10910709
TI  - Entamoeba histolytica: tyrosine kinase activity induced by fibronectin through
      the beta1-integrin-like molecule.
AB  - Previously, we characterized a 140-kDa protein from Entamoeba histolytica as a
      beta1-integrin-like molecule that binds fibronectin. In this work we present data
      showing that the amoebic receptor is associated with another surface molecule,
      the 220-kDa lectin, and with protein tyrosine kinase activity. By
      immunoprecipitation with the alphabeta1Eh antibody, we demonstrated by immune
      complex assays for tyrosine protein kinases that the amoebic fibronectin receptor
      was associated with two phosphorylated proteins of 50 and 70 kDa when internal
      membranes were used as the source of antigen. When cells were stimulated with
      fibronectin, two proteins of 55 and 90 kDa were tyrosine phosphorylated, as shown
      by Western blot with alphaPY20, its phosphorylation being time dependent after
      fibronectin stimulation. However, when the actin cytoskeleton of fibronectin
      stimulated trophozoites was stabilized with phalloidin, the level and the pattern
      of phosphorylated proteins were different. In this case, a high-molecular-weight
      component, heavily phosphorylated, was present, which may include the 220-kDa
      lectin. We also present data confirming that the signaling pathway that is
      activated by fibronectin is specific. This was demonstrated by comparing the
      pattern of phosphoproteins obtained in immune complexes prepared with
      alphabeta1Eh, alphaL220, and alphaPY20 from total extracts obtained in the
      presence of phalloidin, from cells that had been exposed to fibronectin, soluble
      concanavalin A, or concanavalin-A-coated substrate. The presence of tyrosine
      kinases associated with the beta1-integrin-like amoebic molecule was confirmed by
      immunoprecipitation assays along with the combined use of a tyrosine kinase
      specific substrate, the peptide RR-SRC, and a tyrosine kinase inhibitor,
      genistein.

PMID- 10910711
TI  - Schistosoma mansoni: immunodiagnosis is improved by sodium metaperiodate which
      reduces cross-reactivity due to glycosylated epitopes of soluble egg antigen.
AB  - ELISA with soluble egg antigen (SEA) from Schistosoma mansoni is widely used in
      the diagnosis of schistosomiasis, but cross-reactivity with other intestinal
      helminths, overestimating the true prevalence, represents a great limitation. The
      role of glycoproteins of SEA in cross-reactions was investigated. SEA was
      oxidized with sodium metaperiodate (SMP) in ELISA and immunoblot. One hundred
      schistosomiasis-negative individuals sera were submitted to SMP-ELISA improving
      the specificity from 73% without SMP treatment to 97% with SMP. On the other
      hand, 94 S. mansoni-positive sera were evaluated showing that 99% were positive
      in ELISA either with or without SMP treatment, indicating the maintenance of high
      sensitivity under SMP treatment. By immunoblot, 24 sera from persons with
      schistosomiasis and 10 sera from schistosomiasis-free persons were assayed under
      reducing and nonreducing conditions with or without SMP, looking for specific
      infection markers and cross-reactivity markers. Reactivity from positive sera
      showed that specific molecules were mainly low-molecular-mass antigens and seem
      to have predominant proteic epitopes. The unspecific molecules reacting with some
      schistosomiasis-negative individuals harboring other intestinal parasites (false
      positive sera) were mostly larger than 60 kDa and seemed to be basically
      glycosylated. Glycosylated epitopes have an important role in cross-reaction and
      SMP can successfully be used to reduce the false reactivity of SEA with no
      decrease in sensitivity, especially in ELISA as an immunodiagnostic screening
      surveillance method, which is useful in areas of low schistosomiasis
      transmission.

PMID- 10910712
TI  - Plasmodium falciparum: cloned and expressed CIDR domains of PfEMP1 bind to
      chondroitin sulfate A.
AB  - Adherence of erythrocytes infected with mature asexual Plasmodium falciparum
      parasites (iRBC) to microvascular endothelial cells contributes to the pathology
      of P. falciparum malaria. It has been shown that the variant P. falciparum
      erythrocyte membrane protein 1 (PfEMP1) confers adhesion to a wide range of cell
      surface receptors. Previously, the cysteine-rich interdomain region (CIDR) of
      PfEMP1 has been identified as binding site to CD36. We provide evidence that the
      same region can also mediate binding to chondroitin sulfate A (CSA). CIDR domains
      of two different parasite strains were expressed in Escherichia coli as a 6xHis
      tagged protein. Purified recombinant protein bound to Chinese hamster ovary (CHO)
      cells which naturally express chondroitin sulfate A. Treatment of wild-type CHO
      cells with chondroitinase ABC reduced binding up to 94.4%. Competitive binding
      using soluble CSA inhibited binding to CHO cells by up to 100% at 2 mg/ml and by
      62.4% at 0.5 mg/ml, whereas 1 mg/ml heparan sulfate had only a little effect
      (18.1%). In contrast, a recombinant 6xHis-tagged DBL1 domain showed no binding to
      wild-type CHO cells. Such an approach of analyzing various domains of PfEMP1 as
      recombinant proteins may elucidate their functions and may lead to novel anti
      adherence therapeutics, especially for maternal malaria infections.

PMID- 10910710
TI  - Leishmania sp: comparative study with Toxoplasma gondii and Trypanosoma cruzi in
      their ability to initialize IL-12 and IFN-gamma synthesis.
AB  - We compared in vitro and in vivo induction of IL-12 (p40) and IFN-gamma by mouse
      cells stimulated with Toxoplasma gondii, Trypanosoma cruzi, and different species
      of Leishmania. Spleen cells cultured in vitro with T. cruzi or T. gondii, but not
      with Leishmania, produced IL-12 (p40) and IFN-gamma. Accordingly, IL-12 (p40) was
      produced by macrophages stimulated in vitro with live T. cruzi or T. gondii or
      membrane glycoconjugates obtained from trypomastigotes or tachyzoites. No IL-12
      production was detected when macrophages were stimulated with live parasites or
      glycoconjugates from Leishmania, regardless of priming with IFN-gamma. In vivo,
      only T. cruzi and T. gondii induced the synthesis of IL-12 and IFN-gamma by mouse
      spleen cells after intraperitoneal injection of parasites. When injected
      subcutaneously, live Leishmania sp. induced IL-12 (p40) and IFN-gamma production
      by draining lymph node cells, albeit the levels were slightly lower than those
      induced by infection with T. gondii or T. cruzi using the same route. Together
      our results indicate that under different conditions, the intracellular protozoa
      T. gondii and T. cruzi are more potent stimulators of IL-12 and IFN-gamma
      synthesis by host immune cells than parasites of the genus Leishmania.

PMID- 10910713
TI  - Echinococcus granulosus: DNA extraction from germinal layers allows strain
      determination in fertile and nonfertile hydatid cysts.
AB  - A method for the isolation of Echinococcus granulosus DNA from germinal layers of
      hydatid cysts is described. The method includes a hexadecyltrimethylammonium
      bromide/chloroform extraction and an adsorption to diatomaceous earth suspension.
      DNA suitable for polymerase chain reaction was obtained and used for parasite
      strain determination by mitochondrial cytochrome c oxidase I gene sequencing.
      Fertile and nonfertile cyst isolates from sheep, cattle, pigs, and humans were
      characterized. Hitherto, no direct parasite strain characterization has been made
      on nonfertile hydatid cysts, whereas here we report that nonfertile hydatid cysts
      were produced by sheep strain (G1 genotype) in sheep, cattle, and humans and by
      pig strain (G7 genotype) in pigs.

PMID- 10910714
TI  - Giardia lamblia: effect of infection with symptomatic and asymptomatic isolates
      on the growth of gerbils (Meriones unguiculatus).
AB  - Gerbils (Meriones unguiculatus) were intragastrically inoculated with axenic
      Giardia lamblia cultures from symptomatic and asymptomatic children. All isolates
      were able to colonize the duodenum. However, the colonization capacity of the
      symptomatic isolates was significantly higher compared to that of the
      asymptomatic ones. Despite the different colonization capacity of the isolates,
      the growth curves of infected animals were significantly lower than those of
      controls. The study demonstrates that acute giardia infections are capable of
      altering the corporal development of the host. These results may suggest that not
      only symptomatic, but also asymptomatic giardiasis in children, often unnoticed
      by parents and clinicians, could be causing a silent detriment in their
      nutritional status.

PMID- 10910715
TI  - Involvement of platelets in experimental mouse trypanosomiasis: evidence of mouse
      platelet cytotoxicity against Trypanosoma equiperdum.
AB  - Platelets play an important role in the human response to parasites. Trypanosoma
      equiperdum, a parasite that has the horse as its natural host, is able to induce
      infection in mice and thus it may represent a simple model for studying the role
      of platelets in the development of a parasitosis. Although several aspects of the
      murine response to T. equiperdum infection have been clarified, the precise
      mechanism of killing of the parasite is still unclear. We have studied the
      involvement of blood platelets in experimental murine infection with T.
      equiperdum. Infected mice show a progressive decrease of the number of
      circulating platelets. The production of thromboxane A2 (TxA2) by platelets
      stimulated with collagen decreases progressively with the progression of T.
      equiperdum infection, compatible with in vivo platelet activation or with a
      possible antagonistic effect by trypanosomes on the production of TxA2. Finally,
      mouse platelets exert in vitro a direct parasitocidal activity on T. equiperdum
      at ratios >/=20:1. Complement fractions do not enhance platelet trypanocidal
      activity, whereas IgM fractions do, at least in short-term coincubation
      experiments. Our data show that platelets are involved in experimental murine T.
      equiperdum infection and confirm that platelet parasitocidal activity is a
      generalized phenomenon in mammals.

PMID- 10910716
TI  - Immunohistochemical localization of acid proteinase in Ascaris suum adult worm.

PMID- 10910717
TI  - Toxoplasma gondii: are host cell adenosine nucleotides a direct source for purine
      salvage?

PMID- 10910719
TI  - Toxoplasma gondii: purification and characterization of an immunogenic
      metallopeptidase.
AB  - A Toxoplasma gondii aminopeptidase specific for the fluorogenic substrate L
      arginine 7-amino-4-methylcoumarin was identified in cell-free extract. This
      enzyme was purified by high-performance liquid chromatography using first size
      exclusion, then anion exchange, followed by a second size exclusion. The purified
      enzyme exhibited a pl of 4.7 by chromatofocusing and had an apparent molecular
      weight of 110 kDa, as determined by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis under reducing conditions. The purification factor was 80.9 and
      the yield was 14%. The optimal activity was at pH 7.4 and was strongly inhibited
      by EDTA and o-phenanthroline. Antibodies against this T. gondii metallopeptidase
      were detected by immunoprecipitation and immunoblotting in human sera obtained
      from patients undergoing toxoplasmosis.

PMID- 10910718
TI  - Plasmodium falciparum: DBL-1 var sequence analysis in field isolates from central
      Brazil.

PMID- 10910720
TI  - Gag-derived proteins of HIV-1 isolates from Indian patients: cloning, expression,
      and purification of p24 of B- and C-subtypes.
AB  - A simple and efficient method for hyperexpression in Escherichia coli and
      purification of capsid protein, p24, of human immunodeficiency virus type 1 (HIV
      1) of both B- and C-subtypes is described. DNA-encoding p24 of C-subtype was
      cloned from C-subtype gag sequence which was obtained by PCR amplification using
      DNA extracted from peripheral blood mononuclear lymphocytes (PBMLs) of an HIV-1
      infected patient from India. DNA-encoding p24B protein was amplified directly by
      two-step PCR using genomic DNA obtained from PBMLs of an HIV-infected individual.
      A T7 promoter-based expression system was optimized for hyperexpression of p24 in
      the soluble form. Both p24 (B- and C-subtype) were purified to near homogeneity
      using conventional chromatographic techniques. Purification of p24 (C subtype)
      was described for the first time with yield of 53 mg from 1 liter of culture. The
      yield of p24 (B-subtype) was 67 mg from 1 liter of culture, which was severalfold
      better than reported earlier. The immunoreactivity of both types of p24 to sera
      from HIV-infected individuals was comparable. This report describes a simple,
      highly efficient, and reproducible method for obtaining large quantities of
      highly pure p24 of both B- and C-subtype, which can be used for structural,
      biochemical, and immunological characterization and, eventually, for diagnostic
      and prognostic applications.

PMID- 10910722
TI  - Dictyostelium discoideum as expression host: isotopic labeling of a recombinant
      glycoprotein for NMR studies.
AB  - The advantages of the organism Dictyostelium discoideum as an expression host for
      recombinant glycoproteins have been exploited for the production of an
      isotopically labeled cell surface protein for NMR structure studies. Growth
      medium containing [(15)N]NH(4)Cl and [(13)C]glycerol was used to generate
      isotopically labeled Escherichia coli, which was subsequently introduced to D.
      discoideum cells in simple Mes buffer. A variety of growth conditions were
      screened to establish minimal amounts of nitrogen and carbon metabolites for a
      cost-effective protocol. Following single-step purification by anion-exchange
      chromatography, 8 mg of uniformly (13)C,(15)N-labeled protein secreted by
      approximately 10(10) D. discoideum cells was isolated from 3.3 liters of
      supernatant. Mass spectrometry showed the recombinant protein of 16 kDa to have
      incorporated greater than 99.9% isotopic label. The two-dimensional (1)H-(13)C
      HSQC spectrum confirms (13)C labeling of both glycan and amino acid residues of
      the glycoprotein. All heteronuclear NMR spectra showed a good dispersion of cross
      peaks essential for high-quality structure determination.

PMID- 10910721
TI  - Expression, purification, and characterization of equistatin in Pichia pastoris.
AB  - Equistatin (EI) is a cysteine protease inhibitor that was isolated from the sea
      anemone Actinia equina. It belongs to a recently discovered group of
      thyroglobulin type-I domain inhibitors called thyropins. Since native EI is found
      only in low amounts in the body of sea anemone and expression of recombinant EI
      in Escherichia coli yielded only 1 mg/liter of protein, we used the Pichia
      pastoris expression system to obtain higher yields. A cDNA encoding EI was
      inserted into pPIC9 vector and transformed into the P. pastoris, strain GS115.
      Clones expressing high levels of EI were selected from 48 transformants.
      Recombinant EI was produced in 2-liter shake flasks and recovered from the
      fermentation broth by affinity chromatography using CM-papain-Sepharose. SDS-PAGE
      and N-terminal sequence analysis revealed that EI was N-terminally intact and
      running at the expected molecular weight of 22 kDa. The equilibrium dissociation
      constants of EI with papain and bovine cathepsin D were determined and were found
      to be similar to the results for the native inhibitor. EI production was scaled
      up to a bench top fermentor with a 25 mg/liter yield of active EI.

PMID- 10910723
TI  - Purification to homogeneity of Candida albicans glucosamine-6-phosphate synthase
      overexpressed in Escherichia coli.
AB  - The Candida albicans GFA1 gene encoding glucosamine-6-phosphate synthase, an
      enzyme of cell wall biosynthesis pathway in fungi and bacteria, recently an
      object of interest as a target for the chemotherapy of systemic mycoses, was PCR
      amplified and cloned to an Escherichia coli expression vector pET23b. The
      activity of the enzyme in the lysates from the overproducing E. coli strain was
      approximately 50-100 times higher than in the lysates from the control E. coli
      strain. This abundant overproduction allows to purify milligram amounts of the
      enzyme to homogeneity.

PMID- 10910724
TI  - Rapid purification of His(6)-tagged Bacillus subtilis core RNA polymerase.
AB  - Bacillus subtilis core RNA polymerase, containing a His(6)-fusion to the C
      terminus of the beta' subunit, was isolated by Ni-NTA, Superdex 200 gel
      filtration, and Mono Q anion-exchange chromatography. The purified core enzyme
      was shown to be free of the major sigma factor(A) and the transcription factors
      NusA and GreA. The purification procedure can be completed within 1 working day,
      is scalable, and yields highly purified and active core RNA polymerase.

PMID- 10910725
TI  - Purification of the Caenorhabditis elegans transposase Tc1A refolded during gel
      filtration chromatography.
AB  - Full-length recombinant transposase Tc1A from Caenorhabditis elegans (343 amino
      acids) expressed in Escherichia coli BL21 in inclusion bodies has been purified
      in a high yield in a soluble form. The procedure includes denaturation of the
      inclusion bodies followed by refolding of the Tc1A protein by gel filtration.
      This last step is absolutely crucial to give a high yield of soluble and active
      protein since it allows the physical separation of the aggregates from
      intermediates that give rise to correctly refolded protein. This step is very
      sensitive to the concentration of protein. Good yields of refolded protein are
      obtained by refolding 2 to 12 mg of denatured protein. The other purification
      steps involve the initial use of gel filtration under denaturing conditions and a
      final step of ion-exchange chromatography. Biological activity of the purified
      protein was confirmed in an in vitro transposon excision assay and its DNA
      binding capacity by UV crosslinking. This new Tc1A purification procedure gives a
      yield of 12-16 mg/liter E. coli culture, in a form suitable for crystallization
      studies.

PMID- 10910726
TI  - A modified metal-ion affinity chromatography procedure for the purification of
      histidine-tagged recombinant proteins expressed in Drosophila S2 cells.
AB  - We have developed a modified method of immobilized metal-ion affinity
      chromatography (IMAC) that can be used for the purification of histidine-tagged
      proteins from conditioned medium containing free copper ions. Classical methods
      of IMAC purification, using resins such as Ni-NTA, have proven inefficient for
      this type of purification and require multiple steps due to the interference of
      divalent copper ions with the binding of His-tagged protein to the charged resin.
      In contrast, this modified IMAC procedure, using chelating Sepharose instead of
      Ni-NTA, enables efficient purification from copper-containing medium in a single
      step. This method appears to rely upon a preferential interaction of protein
      copper complexes with immobilized chelating resin. We have utilized this method
      to purify active, His-tagged murine interleukin 12 from the conditioned medium of
      Drosophila S2 cells coexpressing recombinant p40 and His-tagged p35 subunits and
      for the purification of the extracellular domain of the erythropoietin receptor.
      This method should be applicable to the purification of a wide variety of His
      tagged fusion proteins expressed in Drosophila cells and in other systems where
      free metal ions are present.

PMID- 10910727
TI  - Expression of human membrane type 1 matrix metalloproteinase in Pichia pastoris.
AB  - A soluble, C-terminal truncated form of human membrane type 1 matrix
      metalloproteinase (MT1-MMP) containing the hemopexin-like domain was expressed in
      Pichia pastoris strain KM71. High levels of secreted protein were detected.
      Although the c-DNA for the proenzyme (Ala(21)-Glu(523) called DeltaTM-MT1-MMP)
      was cloned, almost only active MT1-MMP (Tyr(112)-Glu(523)) with identical N
      terminus as described for the wild-type enzyme was isolated. This active enzyme
      was highly purified and characterized with respect to its biochemical properties.
      The recombinant protein showed high stability against autolysis and proteolysis
      by yeast proteases, although the calculated in vivo half-life is rather low. The
      biochemical properties of this new MT1-MMP species were compared with the well
      characterized catalytic domain (Ile(114)-Ile(318)) of MT1-MMP. The novel form of
      MT1-MMP exhibited a higher stability against autolysis than the isolated
      catalytic domain (Ile(114)-Ile(318)).

PMID- 10910728
TI  - Refolding, purification, and characterization of human recombinant PDE4A
      constructs expressed in Escherichia coli.
AB  - A 5'-truncated PDE4A-cDNA corresponding to the amino acid positions 200-886 of
      the "full-length" sequence (Accession No. L20965) was generated from human
      leukocyte mRNA by RT-PCR. Several PDE4A constructs containing the catalytic
      region and differing in their degree of N- and/or C-terminal truncation (amino
      acid positions 200-886, 200-704, 342-886, and 342-704) were expressed in
      Escherichia coli to investigate the effect of truncations on purification
      characteristics, long-term stability, and aggregation. All peptides accumulated
      as inclusion bodies, necessitating refolding prior to purification by dye and
      metal chelate affinity chromatography. The constructs differed in long-term
      stability due to variable levels of protease contamination. The position of the
      His-tag also influenced the purification results. The best results were obtained
      with the N- and C-truncated form C-terminally His-tagged, appropriate quantities
      of which were obtained in pure form and was found to be stable against
      proteolysis at 4 degrees C for at least 6 weeks. The comparison of the molecular
      mass of the investigated PDE4A constructs obtained by SDS electrophoresis, size
      exclusion chromatography, and analytical ultracentrifugation indicated that C
      terminal truncated PDE4A forms dimers whereas PDE4A constructs with a complete C
      terminus tend to form larger aggregates.

PMID- 10910729
TI  - Functional expression of dipeptidyl peptidase I (Cathepsin C) of the oriental
      blood fluke Schistosoma japonicum in Trichoplusia ni insect cells.
AB  - Proenzyme dipeptidyl peptidase I (DPP I) of Schistosoma japonicum was expressed
      in a baculovirus expression system utilizing Trichoplusia ni BTI-5B1-4 (High
      Five) strain host insect cells. The recombinant enzyme was purified from cell
      culture supernatants by affinity chromatography on nickel-nitriloacetic acid
      resin, exploiting a polyhistidine tag fused to the COOH-terminus of the
      recombinant protease. The purified recombinant enzyme resolved in reducing SDS
      PAGE gels as three forms, of 55, 39, and 38 kDa, all of which were reactive with
      antiserum raised against bacterially expressed S. japonicum DPP I. NH(2)-terminal
      sequence analysis of the 55-kDa polypeptide revealed that it corresponded to
      residues -180 to -175, NH(2)-SRXKXK, of the proregion peptide of S. japonicum DPP
      I. The 39- and 38-kDa polypeptides shared the NH(2)-terminal sequence, LDXNQLY,
      corresponding to residues -73 to -67 of the proregion peptide and thus were
      generated by removal of 126 residues from the NH(2)-terminus of the proenzyme.
      Following activation for 24 h at pH 7.0, 37 degrees C under reducing conditions,
      the recombinant enzyme exhibited exopeptidase activity against synthetic peptidyl
      substrates diagnostic of DPP I. Specificity constants (k(cat)/K(m)) for the
      recombinant protease for the substrates H-Gly-Arg-NHMec and H-Gly-Phe-NHMec were
      found to be 14.4 and 10.7 mM(-)1 s(-1), respectively, at pH 7.0. Approximately 1
      mg of affinity-purified schistosome DPP I was obtained per liter of insect cell
      culture supernatant, representing approximately 2 x 10(9) High Five cells.

PMID- 10910730
TI  - Production and purification of the heavy chain fragment C of botulinum
      neurotoxin, serotype A, expressed in the methylotrophic yeast Pichia pastoris.
AB  - A recombinant H(C) fragment of botulinum neurotoxin, serotype A (rBoNTA(H(C))),
      has been successfully expressed in a Mut(+) strain of the methylotrophic yeast
      Pichia pastoris for use as an antigen in a proposed human vaccine. Fermentation
      employed glycerol batch, glycerol-fed batch, and methanol-fed batch phases to
      achieve high cell density. Induction times were short to maximize rBoNTA(H(C))
      production while minimizing proteolytic degradation. Concentration of
      rBoNTA(H(C)) in yeast cell lysates was generally 1-2% of the total protein based
      on ELISA analysis. The H(C) fragment was purified from cell lysates using a
      multistep ion-exchange (IEC) chromatographic process, including SP, Q, and HS
      resins. The zwitterionic detergent Chaps was included in the buffer system to
      combat possible interactions, such as protein-protein or protein-DNA
      interactions. Following IEC was a hydrophobic interaction chromatography (HIC)
      polishing step, using phenyl resin. The H(C) fragment was purified to >95% purity
      with yields up to 450 mg/kg cells based on ELISA and Bradford protein assay. The
      purified H(C) fragment of serotype A was stable, elicited an immune response in
      mice, and was protected upon challenge with native botulinum type A neurotoxin.

PMID- 10910731
TI  - Bacterial and nonbacterial expression of wild-type and mutant human phospholipid
      hydroperoxide glutathione peroxidase and purification of the mutant enzyme in the
      milligram scale.
AB  - 15-Lipoxygenases and phospholipid hydroperoxide glutathione peroxidases are
      counterparts in the metabolism of hydroperoxy lipids and a balanced regulation of
      both enzymes is essential for normal cell function. Glutathione peroxidases
      contain selenocysteine as catalytically active amino acid and this selenocysteine
      is encoded by a TGA stop codon. Detailed protein chemical investigations on
      phospholipid hydroperoxide glutathione peroxidases and crystal trials have been
      hampered in the past by limited protein supply. There is no efficient natural
      source for large-scale enzyme preparation and overexpression of the functional
      protein in recombinant systems has not been reported so far. To avoid problems
      with recognition of the selenocysteine stop codon we mutated the selenocysteine
      to a cysteine and expressed the Sec46Cys mutant in milligram amounts in the
      baculovirus/insect cell system and as His-tag fusion protein in Escherichia coli.
      The recombinant enzyme species were purified by conventional fast protein liquid
      chromatography (nonfusion protein) or by affinity chromatography on a nickel
      matrix (His-tag protein). Surprisingly, we found that both protein variants were
      functional although their specific activities were reduced when compared with the
      wild-type enzyme. Basic protein chemical and enzymatic properties of the purified
      enzyme species were determined and monoclonal antibodies which recognize the
      native phospholipid hydroperoxide glutathione peroxidases were raised using our
      enzyme preparations as antigen. The described strategies for overexpression of
      mutant phospholipid hydroperoxide glutathione peroxidase species and their
      purification from recombinant sources provide sufficient amounts of enzyme for
      future protein chemical investigations and detailed crystal trials.

PMID- 10910733
TI  - Use of modified BL21(DE3) Escherichia coli cells for high-level expression of
      recombinant peanut allergens affected by poor codon usage.
AB  - We previously cloned a panel of peanut allergens by phage display technology.
      Examination of the codons used in these sequences indicated that most of the
      cDNAs contain an excess of the least used codons in Escherichia coli, namely
      AGG/AGA, that correspond to a minor tRNA, the product of the dnaY gene. To
      achieve high-level expression of the peanut allergens, the cDNAs were subcloned
      into an expression vector of the pET series (Novagen) in order to produce
      (His)(10)-tagged fusion proteins in conventional E. coli BL21(DE3) cells. The
      peanut allergens Ara h 1, Ara h 2, and Ara h 6 with an AGG/AGA codon content of 8
      10% were only marginally expressed, whereas the peanut profilin Ara h 5, with an
      AGG/AGA codon content of only 0.8%, was efficiently expressed in these cells.
      Hence, by using modified BL21(DE3) E. coli cells, namely BL21-CodonPlus(DE3)-RIL
      cells (Stratagene) with extra copies of E. coli argU, ileY, and leuW tRNA genes,
      it was possible to attain high-level expression of the proteins affected by rare
      codon usage. IPTG-induced expression of several recombinant peanut allergens,
      such as Ara h 1, Ara h 2, and Ara h 6, was greatly increased in these special
      cells compared to the expression yield achieved by conventional E. coli hosts.
      The purification of the soluble and the insoluble fraction of Ara h 2 was
      performed by metal-affinity chromatography and yielded a total of about 30 mg
      (His)(10)-tagged recombinant protein per liter of culture of transformed
      BL21(DE3)CodonPlus-RIL cells. This is over 100 times more than achieved by
      production of Ara h 2 in conventional BL21(DE3) cells.

PMID- 10910732
TI  - Overexpression in Escherichia coli and characterization of the chloroplast
      fructose-1,6-bisphosphatase from wheat.
AB  - An important Calvin cycle enzyme, chloroplast fructose-1, 6-bisphosphatase
      (FBPase) from wheat, has been cloned and expressed up to 15% of the total cell
      protein using a pPLc expression vector in Escherichia coli by replacing the
      codons in the 5'-terminal encoding sequence with optimal and A/T-rich ones. The
      overexpressed wheat FBPase is soluble, fully active, and heat stable. It can be
      purified by chromatography in turn on DEAE-Sepharose and Sephacryl S-200, and
      around 15 mg of purified enzymes (>95%) is obtained from 1 liter of cultured
      bacteria. Its special activity is 8.8 u/mg, K(cat) is 22.9/S, K(m) is 121 microM,
      and V(max) is 128 micromol/min. mg. The recombinant FBPase can be activated by
      DTT, Na(+), or low concentrations of Li(+), Ca(2+), Zn(2+), GuHCl, and urea,
      while it can be inhibited by K(+) or NH(+)(4).

PMID- 10910734
TI  - Self-nonself discrimination revisited. Introduction.

PMID- 10910736
TI  - There is only one immune system! The view from immunopathology.
AB  - The generators of B and T cell diversity produce specificities for both
      autochthonous and exogenous paratopes. A wide variety of positive and negative,
      central and peripheral mechanisms has evolved to regulate the immune response.
      All potential immunogens are recognized by the system using the same set of
      'rules', without discrimination between 'self' and 'nonself' or between the
      'toxic' and the 'benign'. In every response, whether positive or negative, the
      factors mobilized and the balance between protection and damage depend upon the
      quality, quantity, location, and timing of immunogen presentation, as well as
      upon properties of the host.

PMID- 10910735
TI  - Localization dose and time of antigens determine immune reactivity.
AB  - Two models to explain patterns of immune reactivity of T and B cells are
      compared: the two-signal theories and the antigen-localization-dose-time and
      structure concept. The two-signal theory states that signal 1 (= antigen alone
      signalling via specific T or B cell receptor) turns T and B cells off, signal 1
      plus co-stimulatory signals 2 induces them. Our model employs immuno-reactivity
      antigen parameters, i.e. localization-dose-time kinetics and structure of antigen
      in determining T and B cell reactivity. Both concepts have in common that immune
      reactivity is somatically learned and not germline defined and that there is
      nothing unique to the antigenic structure itself that could distinguish self from
      nonself antigens. While two-signal theories base positive versus negative
      reactivity on the presence or absence of co-stimulatory signals anywhere in the
      body, our alternative model proposes that besides antigen structure, dose and
      time it is the localization of antigen--vis-a-vis the organized lymphoid tissues-
      that determines reactivity patterns as follows. First, antigen that does not
      reach secondary lymphoid organs in minimum doses or for sufficiently long time
      periods, is immunologically ignored. Second, antigen that either usually exists
      in the lymphoid system or reaches it and persists in excessive amounts for long
      periods deletes T cells. Third, antigen that is transported to secondary lymphoid
      organs in sufficient (but not excessive) amounts and for a sufficient time period
      (but does not persist) induces an effective immune response. B cell responses are
      also induced exclusively in lymphoid tissues. Short-term B cell responses are T
      independent against antigens linked to bacterial lipopolysaccharides or against
      highly repetitive and strictly ordered antigens; thus, B cells are pattern
      recognizers (monomeric antigens usually accessible to B cells are in general
      likely to be self-antigens. Strictly ordered repetitive antigens are virtually by
      definition infectious agents). Long-term (switched) B cell responses against mono
      and polymorphic antigens are T cell dependent regulated by time dose and
      localization of antigen.

PMID- 10910737
TI  - Self/nonself discrimination among immunoregulatory (CD4) T cells.
AB  - This review covers work on immunological tolerance from 1962 up to the present,
      focusing on the Th, CD4+ compartment of the immune system. The principle
      mechanism of tolerance is identified as deletion, occurring centrally and in the
      periphery. In the periphery, deletion is the normal response of CD4 T cells to
      soluble monomeric proteins that occurs when activation (mainly of dendritic
      cells) is avoided. Thus activation and the signals which induce it are crucial to
      understanding S/NS discrimination, as has long been known. The thymus is
      important as the site where new T cells first see self-antigens, and as one
      largely shielded from activation, although deletion in the thymus and the
      periphery has the same threshold. The relative contribution of dendritic cells
      and developing T cells to deletion in the thymus remains unclear. Activation
      induced cell death, containment, anergy and deviation constitute subsidiary
      mechanisms, and sequestration/neglect is important in limiting the scope of
      deletion.

PMID- 10910738
TI  - How does the immune system distinguish self from nonself?

PMID- 10910739
TI  - A minimal model for the self-nonself discrimination: a return to the basics.
AB  - An immune system is required in any host that evolves slowly relative to the
      pathogens that attack it. This immune system must somatically generate and
      regulate new specificities. We propose a mechanism that results in a self-nonself
      discrimination that is a one-time regulatory event, which occurs early in
      development when maternal protection ensures an environment that is free of
      nonself. Our proposed mechanism considers all T and B cells to arise in an i
      state which is incapable of effector reactions. Uniquely in iTh (helpers) a
      prolonged absence of antigen permits their differentiation to eTh (only nonself
      antigens are absent). In all i-state cells antigen induces an anticipatory a
      state which, in the presence of eTh and via associative recognition of antigen
      results in the e-state, and which in the absence of eTh results in cell death.

PMID- 10910740
TI  - Self-tolerance: context dependent tuning of T cell antigen recognition.
AB  - Physiological messages to cells are encoded in the magnitude, and in the time-
      and space-contingencies, of sets of stimuli. In particular, individual T cells
      continuously integrate antigenic and other signals and respond differentially to
      the rate of change in the level of stimulation, translated intracellularly into
      'metabolic perturbations'. The organization of the immune response at the cell
      population level in space and time is also conductive to discriminating the
      magnitude of 'system perturbations'. In this way, the immune system was
      'designed' to respond in a characteristic explosive way mainly to episodes of
      infection and not to the continuous presence of self-antigens. T cells are
      selected to be moderately autoreactive, and the degree of autoreactivity that
      they express is continuously controlled through activation-threshold tuning.
      Their level of autoreactivity is maintained in a range that facilitates survival
      and self-renewal and is probably used in performing some immunoregulatory
      functions and possibly other physiological functions. Autoreactivity and outward
      directed immunity are regulated simultaneously and interactively through the
      interplay of selection, tuning, controlled activation and feedback.

PMID- 10910741
TI  - Germ-line selection ensures embryonic autoreactivity and a positive
      discrimination of self mediated by supraclonal mechanisms.
AB  - It is necessary to clarify principles and mechanisms of natural tolerance to body
      tissues, in order to derive appropriate diagnostics, therapeutics and prognostics
      of autoimmune diseases (AID). I will argue that AIDs result from deficits in
      autoreactive regulatory T cell generation and/or function, and propose a model
      that explains why relatively few prototypes of AID exist, as well as their organ
      specificity or systemic nature. The model suggests that natural tolerance is
      achieved through evolutionarily selected developmental genetic programs: (i) for
      patterns of V-region expression early in life that ensure auto(multi)reactivity
      at the outset of the system; (ii) for a cellular composition of thymic stroma
      that 'breeds' and activates regulatory (autoreactive) T cells in early
      development; (iii) for lymphocyte differentiation and population dynamics, that
      results in peripheral 'education' of regulatory tissue-specific cells, while
      allowing for 'unregulated' clonal responses to nonself. In the present model,
      S/NS discrimination is 'supraclonal' and 'dominant', related to other 'systemic'
      properties such as the regulation of total lymphocyte numbers, the 'open
      endedness' of repertoires, and their differences in health and disease. Dominant
      tolerance models in general, also solve the paradox that pathogenic
      autoreactivity is rare, in spite of the extensive V-region degeneracy of
      lymphocyte recognition and the high frequency of cross-reactivity between S/NS;
      in short, it is astonishing that we are not autoimmune every time we get
      infected. As in other areas of biomedical science, time is perhaps ripe to move
      from component (clonal) analysis to system's biology, as some have proned for
      years.

PMID- 10910742
TI  - Discrimination and dialogue in the immune system.
AB  - This paper presents reasons for concluding that the immune system maintains the
      individual body throughout the vicissitudes of life without the need to make an
      absolute distinction between self and nonself. Self-maintenance and defence
      against parasites both require measured inflammation, and the immune system, in
      both its innate and adaptive arms, regulates inflammation. The intensity,
      dynamics and orchestration of inflammation emerge from an ongoing dialogue.

PMID- 10910743
TI  - Contemporary models for peripheral tolerance and the classical 'historical
      postulate'.
AB  - The formulators of Clonal Selection Theory proposed that what distinguishes self
      from foreign antigens is their early appearance in development, and their
      continuous presence thereafter. This early presence of a self antigen in an
      animals life history was envisaged to ensure that lymphocytes specific for the
      self antigen were silenced rather than activated. I call this idea 'the
      historical postulate'. Contemporary models for the activation/inactivation of
      helper T cells implicitly violate this postulate. I argue against such a
      violation and for a model of T helper cell activation/inactivation that
      reconciles contemporary observations with the postulate.

PMID- 10910744
TI  - Danger: the view from the bottom of the cliff.

PMID- 10910745
TI  - Editorial second thoughts: preamble to round 2.

PMID- 10910746
TI  - Moving beyond the immune self?
AB  - We are witnessing a significant challenge to immunology's basic tenet, the immune
      self. Such an 'entity' is increasingly regarded as polymorphous and ill defined
      as transplantation biology and autoimmunity have demonstrated phenomena that fail
      to allow faithful adherence to a strict dichotomy of self/nonself discrimination.
      Instead of searching for elusive criteria of 'self' and 'other', immune responses
      are increasingly studied as arising within complex contexts, which determine
      various degrees of reactivity or dormancy. When the character of the immune
      'object' is determined by the context in which it appears, not its character as
      'foreign' per se, self/nonself discrimination recedes as a governing principle.
      In such context-based models, 'ecologic' controls arise from the entire organism
      in which the immune system is fully integrated. In these systems, subject-object
      relationships become blurred. Viewed from this perspective, a new theoretical
      construction of the immune system, one originally proposed by Jerne, is
      contending with Burnet's theory of immune identity. Although it is too early to
      judge which theory will prove more capacious, it is already apparent that Jerne's
      formulation has had a decisive impact in shaping new models of immunity.

PMID- 10910747
TI  - Self, intentionality, and immunological explanation.
AB  - In this paper I propose that there are a number of conceptual reasons to preserve
      self-concepts in immunology. First, I contend that immunological language,
      including self-terminology, is neither genuinely anthropomorphic, nor
      perniciously teleological. Furthermore, although teleology associated with future
      directed purposive intent is clearly inappropriate in biological contexts, a
      special type of teleology, intentionality-as-aboutness, needs to be present if
      there is to be functional explanation in immunology. Second, based on an analogy
      with the human self, a self comprised of both non-specific innate functions and
      somatic self-representation, I claim that self-terminology is very appropriate in
      immunological contexts. Finally, given the appropriateness of self-concepts in
      immunology, I suggest that the most satisfactory conceptual structure for self
      nonself discrimination probably includes both innate and somatic mechanisms.

PMID- 10910748
TI  - Silverstein and rose: round 2

PMID- 10910749
TI  - Mitchison, katz, and chain: round 2

PMID- 10910750
TI  - Langman and cohn: round 2

PMID- 10910751
TI  - Hopeful monsters and other ideas

PMID- 10910752
TI  - Irun R. Cohen: round 2

PMID- 10910753
TI  - Bretscher: round 2

PMID- 10910755
TI  - Zinkernagel: round 3

PMID- 10910754
TI  - Anderson and matzinger: round 2

PMID- 10910756
TI  - Silverstein and rose: round 3

PMID- 10910757
TI  - Mitchison, katz, and chain: round 3

PMID- 10910759
TI  - Grossman: round 3

PMID- 10910758
TI  - Langman and cohn: round 3

PMID- 10910760
TI  - Coutinho: round 3

PMID- 10910761
TI  - Cohen: round 3

PMID- 10910762
TI  - Bretscher: round 3

PMID- 10910763
TI  - Anderson and matzinger: round 3

PMID- 10910764
TI  - Editorial summary

PMID- 10910765
TI  - SOCS: physiological suppressors of cytokine signaling.
AB  - Cytokines regulate cellular behavior by interacting with receptors on the plasma
      membrane of target cells and activating intracellular signal transduction
      cascades such as the JAK-STAT pathway. Suppressors of cytokine signaling (SOCS)
      proteins negatively regulate cytokine signaling. The SOCS family consists of
      eight proteins: SOCS1-SOCS7 and CIS, each of which contains a central Src
      homology 2 (SH2) domain and a C-terminal SOCS box. The expression of CIS, SOCS1,
      SOCS2 and SOCS3 is induced in response to stimulation by a wide variety of
      cytokines, and overexpression of these proteins in cell lines results in
      inhibition of cytokine signaling. Thus, SOCS proteins appear to form part of a
      classical negative feedback loop. The analysis of mice lacking SOCS1 has revealed
      that it is critical in the negative regulation of IFN(gamma) signaling and in the
      differentiation of T cells. Additionally, the analysis of mouse embryos lacking
      SOCS3 suggests that SOCS3 negatively regulates fetal liver erythropoiesis,
      probably through its ability to modulate erythropoietin (Epo) signaling. Thus,
      the use of gene targeting has confirmed that SOCS proteins regulate cytokine
      signaling in a physiological setting.

PMID- 10910766
TI  - Cellular Samurai: katanin and the severing of microtubules.
AB  - Recent biochemical studies of the AAA ATPase, katanin, provide a foundation for
      understanding how microtubules might be severed along their length. These in
      vitro studies are complemented by a series of recent reports of direct in vivo
      observation of microtubule breakage, which indicate that the in vitro phenomenon
      of catalysed microtubule severing is likely to be physiological. There is also
      new evidence that microtubule severing by katanin is important for the production
      of non-centrosomal microtubules in cells such as neurons and epithelial cells.
      Although it has been difficult to establish the role of katanin in mitosis, new
      genetic evidence indicates that a katanin-like protein, MEI-1, plays an essential
      role in meiosis in C. elegans. Finally, new proteins involved in the severing of
      axonemal microtubules have been discovered in the deflagellation system of
      Chlamydomonas.

PMID- 10910767
TI  - Amino-terminal domain of classic cadherins determines the specificity of the
      adhesive interactions.
AB  - Classic cadherins are transmembrane receptors involved in cell type-specific
      calcium-dependent intercellular adhesion. The specificity of adhesion is mediated
      by homophilic interactions between cadherins extending from opposing cell
      surfaces. In addition, classic cadherins can self-associate forming lateral
      dimers. Whereas it is widely excepted that lateral dimerization of cadherins is
      critical for adhesion, details of this process are not known. Yet, no evidence
      for physical association between different classic cadherins in cells expressing
      complex cadherin patterns has been reported. To study lateral and adhesive
      intercadherin interactions, we examined interactions between two classic
      cadherins, E- and P-cadherins, in epithelial A-431 cells co-producing both
      proteins. We showed that these cells exhibited heterocomplexes consisting of
      laterally assembled E- and P-cadherins. These complexes were formed by a
      mechanism involving Trp(156) of E-cadherin. Removal of calcium ions from the
      culture medium triggered a novel Trp(156)-independent type of lateral E-cadherin
      P-cadherin association. Notably, an antiparallel (adhesive) mode of interaction
      between these cadherins was negligible. The specificity of adhesive interaction
      was localized to the amino-terminal (EC1) domain of both cadherins. Thus, EC1
      domain of classic cadherins exposes two determinants responsible for nonspecific
      lateral and cadherin type-specific adhesive dimerization.

PMID- 10910768
TI  - RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex:
      involvement of the Ral pathway in receptor endocytosis.
AB  - RLIP76 is a modular protein that was identified as a putative effector of Ral, a
      GTPase activated during Ras signaling. To explore further the contribution of the
      Ral-RLIP76 pathway to Ras signaling, we have looked for partners of RLIP76. Mu2,
      the medium chain of the AP2 complex is shown to interact with RLIP76. We show
      also that in vivo endogenous AP2 and RLIP76 form a complex and that this in vivo
      interaction is independent of cells being stimulated by a growth factor.
      Furthermore, RLIP76 differentiates AP2 from AP1 in vivo as RLIP76 differentiates
      mu2 from mu1 in vitro and in two hybrid assays. We show that activated Ral
      interferes with both tranferrin receptor endocytosis and epidermal growth factor
      (EGF) receptor endocytosis in HeLa cells. We propose a model where the Ral-RLIP76
      pathway connects signal transduction and endocytosis through interaction on one
      hand between the Ras-Ral pathway and RLIP, on the other hand between RLIP and
      proteins belonging to the endocytotic machinery.

PMID- 10910769
TI  - Nuclear translocation and aggregate formation of heat shock cognate protein 70
      (Hsc70) in oxidative stress and apoptosis.
AB  - Recent evidence has shown a role for the heat shock cognate protein Hsc70 in the
      response to oxidative stress. We have investigated the subcellular distribution
      of Hsc70 by means of laser scanning confocal microscopy in neuroblastoma NB41A3
      cells, in fibroblasts R6 cells and in R6-Bcl-2, an apoptosis-resistant cell line,
      and its function in oxidative stress and in apoptosis has been evaluated.
      Endogenous Hsc70 is localised predominantly in the cytoplasm in unstressed cells,
      whereas oxidative stress but not apoptosis induces its translocation into the
      nucleus. In transfected cells overexpressing Hsc70 increased nuclear
      translocation and aggregation of Hsc70 in intracellular speckles is observed
      after oxidative stress and, to a lesser degree, after exposure to apoptotic
      agents. Bcl-2 did not influence the movement of Hsc70 nor the formation of Hsc70
      containing speckles. Nuclear translocation of Hsc70 can be modulated by the
      expression of components from a previously described plasma membrane
      oxidoreductase involved in the cellular response against oxidative stress. Our
      data may suggest a correlation between differential translocation of Hsc70 with
      specific functions in apoptosis and a potential role in the protection against
      reactive oxygen species.

PMID- 10910770
TI  - The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat
      aorta smooth muscle cells are inhibited by basic fibroblast growth factor.
AB  - In response to endovascular injury, platelet-derived growth factor-BB (PDGF-BB)
      and basic fibroblast growth factor (bFGF) are released locally and modulate
      vascular smooth muscle cells (SMC) proliferation and migration within the
      vascular wall. The aim of the present in vitro study was to determine how rat
      aorta SMC respond to the simultaneous exposure to PDGF-BB and bFGF. In a modified
      Boyden chamber assay bFGF exhibited a dose-dependent effect to inhibit the
      chemotactic action of PDGF-BB. A comparable result was observed in proliferation
      assays. In contrast, MIP-1 beta, epidermal growth factor (EGF), fibronectin and
      acidic FGF (aFGF) did not inhibit the chemotactic effect of PDGF-BB. Denatured
      bFGF did not exert an inhibitory effect and neutralizing antibodies either to
      bFGF or to bFGF-receptor abolished the inhibition observed in the presence of
      bFGF. The role played by PDGF receptor alpha (PDGF-Ralpha) was investigated in
      PDGF-Ralpha-dominant negative-transfected SMC, by selectively blocking PDGF-BB
      binding to PDGF-Ralpha with neomycin, by neutralizing PDGF-Ralpha with a
      monoclonal antibody and by selectively stimulating PDGF-Ralpha with PDGF-AA; in
      all cases the effect of bFGF to inhibit PDGF-BB-directed SMC migration was
      abolished. These in vitro studies show that bFGF significantly inhibits PDGF-BB
      induced SMC migration and proliferation and that this effect is mediated by both
      PDGF-Ralpha and bFGF receptor.

PMID- 10910771
TI  - Signaling specificities of fibroblast growth factor receptors in early Xenopus
      embryo.
AB  - Formation of mesoderm and posterior structures in early Xenopus embryos is
      dependent on fibroblast growth factor (FGF) signaling. Although several FGF
      receptors (FGFRs) are expressed in the early embryo, their respective role in
      these processes remains poorly understood. We provide evidence that FGFR-1 and
      FGFR-4 signals elicit distinct responses both in naive and neuralized ectodermal
      cells. We show that naive ectodermal cells expressing a constitutively active
      chimeric torso-FGFR-1 (t-R1) are converted into mesoderm in a Ras-dependent
      manner, while those expressing torso-FGFR-4 (t-R4) differentiate into epidermis
      without significant activation of Erk-1. In neuralized ectoderm, expression of t
      R4 causes the up-regulation of the midbrain markers En-2 and Wnt-1, but not of
      the hindbrain nor the spinal cord markers Krox20 and Hoxb9. Mutation of tyr(776)
      in the phospholipase C-(gamma) binding consensus sequence YLDL of t-R4 completely
      abolishes En-2 and Wnt-1 induction. In contrast to t-R4, platelet derived growth
      factor (PDGF)-dependent FGFR-1 activation in neuralized ectodermal cells
      expressing a chimeric PDGFR-FGFR-1 receptor results in the expression of Krox20
      and Hoxb9. A similar effect is observed when an inducible form of oncogenic Raf
      is expressed, therefore implicating FGFR-1 and Raf in the transduction of FGF
      caudalizing signals in neural tissue. Our results suggest that FGFR-1 and FGFR-4
      transduce distinct signals in embryonic cells, and mainly differ in their ability
      to activate the Ras/MAPK pathway.

PMID- 10910772
TI  - Laminin and alpha7beta1 integrin regulate agrin-induced clustering of
      acetylcholine receptors.
AB  - The clustering of acetylcholine receptors (AChRs) in the post-synaptic membrane
      of skeletal muscle is an early developmental event in the formation of the
      neuromuscular junction. Several studies show that laminin, as well as neural
      agrin, can induce AChR clustering in C2C12 myofibers. We recently showed that
      specific isoforms of the alpha7beta1 integrin (a receptor normally found at
      neuromuscular junctions) colocalize and physically interact with AChR clusters in
      a laminin-dependent fashion. In contrast, induction with agrin alone fails to
      promote localization of the integrin with AChR clusters. Together both agrin and
      laminin enhance the interaction of the integrin with AChRs and their aggregation
      into clusters. To further understand this mechanism we investigated cluster
      formation and the association of the alpha7beta1 integrin and AChR over time
      following induction with laminin and/or agrin. Our results show that the
      alpha7beta1 integrin associates with AChRs early during the formation of the post
      synaptic membrane and that laminin modulates this recruitment. Laminin induces a
      rapid stable association of the integrin and AChRs and this association is
      independent of clustering. In addition to laminin-1, merosin (laminin-2/4) is
      present both before and after formation of neuromuscular junctions and also
      promotes AChR clustering and colocalization with the integrin as well as
      synergism with agrin. Using site directed mutagenesis we demonstrate that a
      tyrosine residue in the cytoplasmic domain of both (&agr;)7A and (&agr;)7B chains
      regulates the localization of the integrin with AChR clusters. We also provide
      evidence that laminin, through its association with the alpha7beta1 integrin,
      reduces by 20-fold the concentration of agrin required to promote AChR clustering
      and accelerates the formation of clusters. Thus laminin, agrin and the
      alpha7beta1 integrin act in a concerted manner early in the development of the
      post-synaptic membrane, with laminin priming newly formed myofibers to rapidly
      and vigorously respond to low concentrations of neural agrin produced by
      innervating motor neurons.

PMID- 10910773
TI  - The conserved amphipatic alpha-helical core motif of RARgamma and RARalpha
      activating domains is indispensable for RA-induced differentiation of F9 cells.
AB  - In monolayers cultures, retinoic acid (RA) induces the differentiation of F9
      embryonal carcinomal (EC) cells into primitive endoderm-like cells, while a
      combination of RA and dibutyryl cAMP leads to parietal endoderm-like
      differentiation. Knock out of all RARgamma isoforms (RARgamma(-/-) line)
      drastically impairs primitive and subsequent parietal endodermal differentiation
      and affects the induction of many endogenous RA-responsive genes. Using lines
      that reexpress RARgamma2 or overexpress RARalpha1 lacking their AF-2AD core
      (RARgammadeltaAF2 and RARalphadeltaAF2, respectively), we show that this
      conserved amphipatic alpha-helical motif (helix 12) of the ligand binding domain,
      and therefore the activation function AF-2 of both receptors, is required for the
      induction of differentiation and target gene expression upon RA treatment of F9
      EC cells. We also show that these deletion mutants behave as dominant negatives.

PMID- 10910774
TI  - Somatic linker histone H1 is present throughout mouse embryogenesis and is not
      replaced by variant H1 degrees.
AB  - A striking feature of early embryogenesis in a number of organisms is the use of
      embryonic linker histones or high mobility group proteins in place of somatic
      histone H1. The transition in chromatin composition towards somatic H1 appears to
      be correlated with a major increase in transcription at the activation of the
      zygotic genome. Previous studies have supported the idea that the mouse embryo
      essentially follows this pattern, with the significant difference that the
      substitute linker histone might be the differentiation variant H1 degrees, rather
      than an embryonic variant. We show that histone H1 degrees is not a major linker
      histone during early mouse development. Instead, somatic H1 was present
      throughout this period. Though present in mature oocytes, somatic H1 was not
      found on maternal metaphase II chromatin. Upon formation of pronuclear envelopes,
      somatic H1 was rapidly incorporated onto maternal and paternal chromatin, and the
      amount of somatic H1 steadily increased on embryonic chromatin through to the 8
      cell stage. Microinjection of somatic H1 into oocytes, and nuclear transfer
      experiments, demonstrated that factors in the oocyte cytoplasm and the nuclear
      envelope, played central roles in regulating the loading of H1 onto chromatin.
      Exchange of H1 from transferred nuclei onto maternal chromatin required breakdown
      of the nuclear envelope and the extent of exchange was inversely correlated with
      the developmental advancement of the donor nucleus.

PMID- 10910775
TI  - Mouse keratinocytes immortalized with large T antigen acquire alpha3beta1
      integrin-dependent secretion of MMP-9/gelatinase B.
AB  - Remodeling of the extracellular matrix during tissue development, wound repair
      and tumor cell invasion depends on the coordinated regulation of cell adhesion
      receptors, matrix proteins and enzymes that proteolyse the extracellular matrix.
      Integrin alpha3beta1 is a major receptor on epidermal keratinocytes for laminin-5
      in the cutaneous basement membrane and is required for normal basement membrane
      organization during skin development. alpha3beta1 is also expressed at high
      levels in the majority of adherent transformed cells and in most tumors, and it
      could have similar roles in extracellular matrix remodeling during tumorigenesis
      and cell invasion. In the present study, we show that alpha3beta1 expression is
      required in immortalized mouse keratinocytes (MK) for the production of the
      matrix metalloproteinase MMP-9/gelatinase B, an MMP that is coexpressed with
      alpha3beta1 in epithelial cell carcinomas and during wound healing, and
      contributes to the invasive potential of some tumor cells. MMP-9 was expressed in
      MK cells derived from wild-type mice, but not in MK cells derived from alpha3
      null mice. Reconstitution of alpha3beta1 expression in alpha3-null MK cells
      through transfection with the alpha3 subunit restored MMP-9 secretion, indicating
      an alpha3beta1-dependent pathway for MMP-9 production. alpha3beta1-dependent
      expression of MMP-9 was associated with the immortalized phenotype, since
      nonimmortalized, primary keratinocytes required soluble growth factors, but not
      alpha3beta1, for efficient expression of MMP-9. Our results suggest that an
      alpha3beta1-independent pathway(s) for MMP-9 production is suppressed in
      keratinocytes immortalized with large T antigen, and that an alpha3beta1
      dependent pathway is required for sustained production of MMP-9 in the absence of
      other pathways.

PMID- 10910776
TI  - Integration of nature and nurture: a new paradigm for psychiatry.

PMID- 10910777
TI  - Classifying depression: should paradigms lost be regained?
AB  - OBJECTIVE: Classification of the depressive disorders has long been
      controversial. The dominant current model is unitarian, with disorders largely
      distinguished on the basis of severity. Both the unitarian and the contrasting
      binarian views (of two principal types) have proved to be unsatisfactory. The
      binarian model's procrustean requirements are too inflexible to address the
      evident heterogeneity contributed to by clinical manifestations and underlying
      personality features. METHOD: This article briefly reviews the historically
      favored unitarian and binarian viewpoints on classification of depression.
      RESULTS: The author argues that the "final common pathway" model, articulated in
      the early 1970s, helped to cement psychiatric classification in subsequent DSM
      and ICD revisions into a unitarian framework, leading to a relatively sterile
      period of depression research. Clinically described depressive typologies were
      obscured rather than refined by appropriate modeling paradigms. A contrasting,
      empirically based hierarchical model, driven by disorder-specific clinical
      manifestations such as psychotic features and observable psychomotor disturbance,
      is proposed as a paradigm for distinguishing psychotic, melancholic, and
      nonmelancholic classes of depression, while a spectrum model is favored for
      distinguishing the principal nonmelancholic subclasses. CONCLUSIONS: Resolution
      of the better paradigm requires that the two models undergo comparative testing
      in applied studies, particularly ones pursuing neurobiological determinants and
      differential responses to antidepressant treatments.

PMID- 10910778
TI  - Flawed meta-analyses comparing psychotherapy with pharmacotherapy.
AB  - OBJECTIVE: The author sought to illustrate the invalidity of meta-analyses that
      claim to quantitatively compare the benefits of psychotherapy to pharmacotherapy
      in patients with psychiatric disorders. METHOD: Studies included in four meta
      analyses were retrieved and their study designs evaluated. RESULTS: The meta
      analyses compared effect sizes from disparate studies that were not uniformly
      blind, random, controlled, or of high quality. The studies did not directly
      address the comparative efficacy question or lacked assay sensitivity.
      CONCLUSIONS: Numerous types of studies exemplify the need for caution in
      evaluating meta-analytic conclusions without first critically examining the
      included studies. Estimates of the relative efficacy of different treatments are
      not well founded when based almost exclusively on indirect, multiply confounded
      comparisons. Meta-analyses based on flawed studies or studies that lack
      demonstrated assay sensitivity are also inadequate for the criticism of treatment
      guidelines. Some bodies of data are inadequate to support a proper meta-analysis.

PMID- 10910779
TI  - Images in neuroscience. Neural networks: neural systems II.

PMID- 10910781
TI  - Twin sisters with psychotic disorders.

PMID- 10910783
TI  - Impact of stressful life events, depression, social support, coping, and cortisol
      on progression to AIDS.
AB  - OBJECTIVE: This study examined prospectively the effects of stressful events,
      depressive symptoms, social support, coping methods, and cortisol levels on
      progression of HIV-1 infection. METHOD: Eighty-two homosexual men with HIV type-1
      infection without AIDS or symptoms at baseline were studied every 6 months for up
      to 7. 5 years. Men were recruited from rural and urban areas in North Carolina,
      and none was using antiretroviral medications at entry. Disease progression was
      defined as CD4(+) lymphocyte count <200/microl or the presence of an AIDS
      indicator condition. RESULTS: Cox regression models with time-dependent
      covariates were used adjusting for race, baseline CD4(+) count and viral load,
      and cumulative average antiretroviral medications. Faster progression to AIDS was
      associated with higher cumulative average stressful life events, coping by means
      of denial, and higher serum cortisol as well as with lower cumulative average
      satisfaction with social support. Other background (e.g., age, education) and
      health habit variables (e.g., tobacco use, risky sexual behavior) did not
      significantly predict disease progression. The risk of AIDS was approximately
      doubled for every 1.5-unit decrease in cumulative average support satisfaction
      and for every cumulative average increase of one severe stressor, one unit of
      denial, and 5 mg/dl of cortisol. CONCLUSIONS: Further research is needed to
      determine if treatments based on these findings might alter the clinical course
      of HIV-1 infection.

PMID- 10910784
TI  - Stress and vulnerability to posttraumatic stress disorder in children and
      adolescents.
AB  - OBJECTIVE: This study examined the experiential factors and interacting
      vulnerabilities that contribute to the development of posttraumatic stress
      disorder (PTSD) in children and adolescents. METHOD: Of 100 consecutive referrals
      to an inner-city child and adolescent psychiatry clinic, 59 had experienced a
      trauma that qualified as a precipitant of PTSD. For those with trauma, ages
      ranged from 3 to 18 years (mean=9.9, SD=4.10); 39 (66%) were males. The authors
      used a series of multiple regression analyses to examine the contribution of
      demographic characteristics, the nature of the stressor(s), and the role of
      preexisting clinical signs in the development of PTSD. RESULTS: Twenty-two
      percent of the 59 children who had been traumatized met full criteria for PTSD,
      32% had some symptoms of PTSD but did not meet full criteria, and 46% had no
      symptoms of PTSD. Witnessing domestic violence or being physically abused
      predicted severity of PTSD. Children with preexisting aggressive behavior were
      more likely to be victims of physical abuse. CONCLUSIONS: Traumatic experience
      interacts with factors in the child and family to contribute to the development
      of PTSD. Trauma that threatens family integrity appears to make a strong
      contribution to the development of PTSD. Increased understanding of the factors
      contributing to PTSD may provide additional opportunities for developing
      effective interventions.

PMID- 10910786
TI  - Stressful life events and previous episodes in the etiology of major depression
      in women: an evaluation of the "kindling" hypothesis.
AB  - OBJECTIVE: Although previous evidence has suggested that the etiologic role of
      stressful life events in major depression is reduced in recurrent versus first
      onset cases, this question deserves reexamination because of potential
      methodological limitations of the previous studies. METHOD: Members of female
      female twin pairs from a population-based registry (N=2,395), who were
      interviewed four times over a period of 9 years, formed a study group that
      contained 97,515 person-months and 1,380 onsets of major depression. Discrete
      time survival, proportional hazards model, and piece-wise regression analyses
      were used to examine the interaction between life event exposure and number of
      previous depressive episodes in the prediction of episodes of major depression.
      RESULTS: For those with zero to nine previous depressive episodes, the
      depressogenic effect of stressful life events declined substantially with
      increasing episode number. However, the association between stressful life events
      and major depression was not substantially influenced by additional episodes.
      This pattern of results was robust to the addition of indices of event severity,
      measures of genetic risk, and restriction to independent stressful life events.
      The same pattern was also seen upon examining within-person changes in number of
      episodes. CONCLUSIONS: The association between previous number of depressive
      episodes and the pathogenic impact of stressful life events on major depression
      is likely causal and biphasic. Through approximately nine episodes, the
      association between stressful life event exposure and risk of major depression
      progressively declines but is largely unchanged with further episodes. These
      results are consistent with the kindling hypothesis but suggest a threshold at
      which the mind/brain is no longer additionally sensitized to the depressive
      state.

PMID- 10910785
TI  - Yohimbine challenge in children with anxiety disorders.
AB  - OBJECTIVE: The authors evaluated the neurohormonal and subjective mood response
      of children with anxiety disorders who were challenged with yohimbine. METHOD:
      Seventeen children with DSM-IV diagnoses of anxiety disorders and 15 normal
      comparison children were given yohimbine orally (0.1 mg/kg). Neurohormonal
      measures and visual analog self-reports of tenseness were recorded over a 150
      minute period. RESULTS: Yohimbine was uniformly well tolerated, and it
      behaviorally differentiated children with anxiety disorders from normal
      comparison children with higher maximum change (Deltamax) ratings of anxiety in
      the patients (mean=17.4 mm, SD=29.8) than in the comparison subjects (mean=0.3
      mm, SD=4.4). Yohimbine-stimulated Deltamax growth hormone (GH) for children with
      anxiety disorders (mean=-1.5 ng/ml, SD=5.9) was significantly reduced compared to
      that of normal comparison children (mean=2.7 ng/ml, SD=4.5). CONCLUSIONS:
      Yohimbine selectively elevates self-rated anxiety in children with anxiety
      disorders and is associated with the blunting of GH in those children relative to
      that of comparison children. Presence of a blunted GH response to yohimbine in
      children with anxiety disorders is reminiscent of findings in adults with anxiety
      disorders, particularly panic disorder. These findings support enhanced central
      adrenergic sensitivity in children with anxiety disorders, as demonstrated by
      yohimbine-exacerbated anxiety. The findings should be reconciled with the absence
      of clonidine-related GH blunting in the same cohort.

PMID- 10910787
TI  - Low cortisol and risk for PTSD in adult offspring of holocaust survivors.
AB  - OBJECTIVE: The study examined the association between cortisol and putative risk
      factors for posttraumatic stress disorder (PTSD) in a sample of subjects at
      increased risk for the development of PTSD. METHOD: Twenty-four-hour urinary
      cortisol excretion was measured in 35 adult offspring of Holocaust survivors and
      15 healthy comparison subjects who were not offspring of Holocaust survivors.
      Subjects were also characterized with regard to clinical symptoms, presence or
      absence of psychiatric diagnoses including PTSD, and presence or absence of PTSD
      in their parents. RESULTS: Low cortisol levels were significantly associated with
      both PTSD in parents and lifetime PTSD in subjects, whereas having a current
      psychiatric diagnosis other than PTSD was relatively, but nonsignificantly,
      associated with higher cortisol levels. Offspring with both parental PTSD and
      lifetime PTSD had the lowest cortisol levels of all study groups. CONCLUSIONS:
      Parental PTSD, a putative risk factor for PTSD, appears to be associated with low
      cortisol levels in offspring, even in the absence of lifetime PTSD in the
      offspring. The findings suggest that low cortisol levels in PTSD may constitute a
      vulnerability marker related to parental PTSD as well as a state-related
      characteristic associated with acute or chronic PTSD symptoms.

PMID- 10910788
TI  - Longitudinal study of earthquake-related PTSD in a randomly selected community
      sample in north China.
AB  - OBJECTIVE: This study longitudinally described rates of posttraumatic stress
      disorder (PTSD) in two groups with different levels of severity of exposure to an
      earthquake in North China. The effects of diagnostic criteria on the frequency of
      detected PTSD were also examined. METHOD: Subjects were randomly sampled in two
      villages at different distances from the earthquake epicenter. A total of 181 and
      157 subjects were assessed at 3 months and 9 months after the earthquake,
      respectively, for PTSD by using both DSM-IV and DSM-III-R criteria. The brief
      version of the World Health Organization Quality of Life Assessment and three
      subscales of the SCL-90-R were also administered at both assessment points.
      RESULTS: The village with a higher level of initial exposure to the earthquake
      and a higher level of postearthquake support had a lower frequency of PTSD than
      the village with a lower level of initial exposure and less postearthquake
      support. The rate of onset of DSM-IV PTSD within 9 months for the two villages
      was 19.8% and 30.3%, respectively. In both villages, the rate of onset of
      earthquake-related PTSD within 9 months was 24.2% by using DSM-IV criteria and
      41.4% by using DSM-III-R criteria. The introduction in DSM-IV of a criterion
      requiring clinically significant distress or impairment in functioning for a
      diagnosis of PTSD was a major contributor to the lower rate of DSM-IV PTSD.
      CONCLUSIONS: PTSD may be as prevalent and persistent in disaster victims in China
      as in those elsewhere. Prompt and effective postdisaster intervention could
      mitigate the impact of initial exposure and reduce the probability of PTSD
      occurrence. Caution should be used in comparing rates of postdisaster PTSD
      identified by using different diagnostic criteria.

PMID- 10910790
TI  - Health and disability costs of depressive illness in a major U.S. corporation.
AB  - OBJECTIVE: Employers are playing an increasingly influential role in determining
      the scope and character of health coverage in the United States. This study
      compares the health and disability costs of depressive illness with those of four
      other chronic conditions among employees of a large U.S. corporation. METHOD:
      Data from the health and employee files of 15,153 employees of a major U.S.
      corporation who filed health claims in 1995 were examined. Analyses compared the
      mental health costs, medical costs, sick days, and total health and disability
      costs associated with depression and four other conditions: heart disease,
      diabetes, hypertension, and back problems. Regression models were used to control
      for demographic differences and job characteristics. RESULTS: Employees treated
      for depression incurred annual per capita health and disability costs of $5,415,
      significantly more than the cost for hypertension and comparable to the cost for
      the three other medical conditions. Employees with depressive illness plus any of
      the other conditions cost 1.7 times more than those with the comparison medical
      conditions alone. Depressive illness was associated with a mean of 9.86 annual
      sick days, significantly more than any of the other conditions. Depressed
      employees under the age of 40 years took 3.5 more annual sick days than those 40
      years old or older. CONCLUSIONS: The cost of depression to employers,
      particularly the cost in lost work days, is as great or greater than the cost of
      many other common medical illnesses, and the combination of depressive and other
      common illnesses is particularly costly. The strong association between
      depressive illness and sick days in younger workers suggests that the impact of
      depression may increase as these workers age.

PMID- 10910789
TI  - Changing patterns of psychiatric inpatient care for children and adolescents in
      general hospitals, 1988-1995.
AB  - OBJECTIVE: The authors examine patterns in utilization of psychiatric inpatient
      services by children and adolescents in general hospitals during 1988-1995.
      METHOD: National Hospital Discharge Survey data were used to describe utilization
      patterns for children and adolescents with primary psychiatric diagnoses in
      general hospitals from 1988 to 1995. RESULTS: During the study period, there was
      a 36% increase in hospital discharges and a 44% decline in mean length of stay,
      resulting in a 23% decline in the number of bed-days, from more than 3 million to
      about 2.5 million. The number of nonpsychotic major depressive disorders
      increased significantly. Discharges from public hospitals have declined, and
      those from proprietary hospitals have risen. Concurrently, the role of private
      insurance declined and the role of Medicaid increased. During the period of
      study, the mean and median length of stay declined most for children and
      adolescents who were hospitalized in private facilities and those covered by
      private insurance. Across the United States, the mean length of stay declined
      significantly; this decline was almost 60% in the West. Discharges also declined
      in the West, in contrast to the Midwest and the South, where they significantly
      increased. CONCLUSIONS: Increased numbers of discharges and decreased length of
      stay may reflect evolving market forces and characteristics of hospitals. Further
      penetration by managed care into the public insurance system or modifications in
      existing Medicaid policy could have a profound impact on the availability of
      inpatient resources.

PMID- 10910791
TI  - Hypnotic visual illusion alters color processing in the brain.
AB  - OBJECTIVE: This study was designed to determine whether hypnosis can modulate
      color perception. Such evidence would provide insight into the nature of hypnosis
      and its underlying mechanisms. METHOD: Eight highly hypnotizable subjects were
      asked to see a color pattern in color, a similar gray-scale pattern in color, the
      color pattern as gray scale, and the gray-scale pattern as gray scale during
      positron emission tomography scanning by means of [(15)O]CO(2). The classic color
      area in the fusiform or lingual region of the brain was first identified by
      analyzing the results when subjects were asked to perceive color as color versus
      when they were asked to perceive gray scale as gray scale. RESULTS: When subjects
      were hypnotized, color areas of the left and right hemispheres were activated
      when they were asked to perceive color, whether they were actually shown the
      color or the gray-scale stimulus. These brain regions had decreased activation
      when subjects were told to see gray scale, whether they were actually shown the
      color or gray-scale stimuli. These results were obtained only during hypnosis in
      the left hemisphere, whereas blood flow changes reflected instructions to
      perceive color versus gray scale in the right hemisphere, whether or not subjects
      had been hypnotized. CONCLUSIONS: Among highly hypnotizable subjects, observed
      changes in subjective experience achieved during hypnosis were reflected by
      changes in brain function similar to those that occur in perception. These
      findings support the claim that hypnosis is a psychological state with distinct
      neural correlates and is not just the result of adopting a role.

PMID- 10910792
TI  - Do the dimensions of the temperament and character inventory map a simple genetic
      architecture? Evidence from molecular genetics and factor analysis.
AB  - OBJECTIVE: It has been reported that the human temperament dimensions of novelty
      seeking and harm avoidance are associated with polymorphisms in the D(4) dopamine
      receptor gene (D4DR) and the serotonin-transporter-linked promoter region (5
      HTTLPR), respectively. Although these findings are consistent with Cloninger's
      hypothesized psychobiological model of temperament and character, many studies
      failed to replicate these findings. In the present study the authors tested
      whether the psychobiological model taps the genetic architecture of personality
      by exploring associations between these candidate genes and the dimensions of the
      Temperament and Character Inventory and by examining its phenotypic structure.
      METHOD: Of the 946 male and female participants in the Baltimore Longitudinal
      Study of Aging to whom the Temperament and Character Inventory was administered,
      587 were genotyped for a polymorphism with a 48-base-pair repeat in the D4DR gene
      and 425 were genotyped for a 44-base-pair insertion or deletion in the 5-HTTLPR
      polymorphism. RESULTS: There was no significant association between D4DR
      polymorphisms and novelty seeking. The authors also failed to find an association
      between 5-HTTLPR polymorphisms and harm avoidance. The factor structure of the
      Temperament and Character Inventory did not reveal the hypothesized phenotypic
      structure. CONCLUSIONS: This investigation produced no support for the
      temperament-character model at either the biological or psychological level.

PMID- 10910793
TI  - Muscle dysmorphia in male weightlifters: a case-control study.
AB  - OBJECTIVE: Muscle dysmorphia is a form of body dysmorphic disorder in which
      individuals develop a pathological preoccupation with their muscularity. METHOD:
      The authors interviewed 24 men with muscle dysmorphia and 30 normal comparison
      weightlifters, recruited from gymnasiums in the Boston area, using a battery of
      demographic, psychiatric, and physical measures. RESULTS: The men with muscle
      dysmorphia differed significantly from the normal comparison weightlifters on
      numerous measures, including body dissatisfaction, eating attitudes, prevalence
      of anabolic steroid use, and lifetime prevalence of DSM-IV mood, anxiety, and
      eating disorders. The men with muscle dysmorphia frequently described shame,
      embarrassment, and impairment of social and occupational functioning in
      association with their condition. By contrast, normal weightlifters displayed
      little pathology. Indeed, in an a posteriori analysis, the normal weightlifters
      proved closely comparable to a group of male college students recruited as a
      normal comparison group in an earlier study. CONCLUSIONS: Muscle dysmorphia
      appears to be a valid diagnostic entity, possibly related to a larger group of
      disorders, and is associated with striking and stereotypical features. Men with
      muscle dysmorphia differ sharply from normal weightlifters, most of whom display
      little psychopathology. Further research is necessary to characterize the
      nosology and potential treatment of this syndrome.

PMID- 10910794
TI  - Body image perception among men in three countries.
AB  - OBJECTIVE: The authors tested the hypothesis that men in modern Western societies
      would desire to have a much leaner and more muscular body than the body they
      actually had or perceived themselves to have. METHOD: The height, weight, and
      body fat of college-aged men in Austria (N=54), France (N=65), and the United
      States (N=81) were measured. Using the somatomorphic matrix, a computerized test
      devised by the authors, the men chose the body image that they felt represented
      1) their own body, 2) the body they ideally would like to have, 3) the body of an
      average man of their age, and 4) the male body they believed was preferred by
      women. The men's actual fat and muscularity was compared with that of the four
      images chosen. RESULTS: Only slight demographic and physical differences were
      found among the three groups of men. Modest differences were found between the
      men's measured fat and the fat of the images chosen. However, measures of
      muscularity produced large and highly significant differences. In all three
      countries, men chose a ideal body that was a mean of about 28 lb (13 kg) more
      muscular than themselves and estimated that women preferred a male body about 30
      lb (14 kg) more muscular than themselves. In a pilot study, however, the authors
      found that actual women preferred an ordinary male body without added muscle.
      CONCLUSIONS: The wide discrepancy between men's actual muscularity and their body
      ideals may help explain the apparent rise in disorders such as muscle dysmorphia
      and anabolic steroid abuse.

PMID- 10910795
TI  - Outcome predictors for the cognitive behavior treatment of bulimia nervosa: data
      from a multisite study.
AB  - OBJECTIVE: The aim of this study was to discover clinically useful predictors of
      attrition and outcome in the treatment of bulimia nervosa with cognitive behavior
      therapy. METHOD: Pretreatment, course of treatment, and outcome data were
      gathered on 194 women meeting the DSM-III-R criteria for bulimia nervosa who were
      treated with 18 sessions of manual-based cognitive behavior therapy in a three
      site study. Differences between dropouts and nondropouts and between recovered
      and nonrecovered participants were first examined descriptively, and signal
      detection analyses were then used to determine clinically significant cutoff
      points predicting attrition and abstinence. RESULTS: The dropouts were
      characterized by more severe bulimic cognitions and greater impulsivity, but it
      was not possible to identify clinically useful predictors. The participants with
      treatment failures were characterized by poor social adjustment and a lower body
      mass index, presumably indicating greater dietary restriction. However, early
      progress in therapy best predicted outcome. Signal detection analyses revealed
      that poor outcome was predicted by a reduction in purging of less than 70% by
      treatment session 6, allowing identification of a substantial proportion of
      prospective failures. CONCLUSIONS: A cutoff point based on reduction of purging
      by session 6 usefully differentiates patients who will and will not respond to
      cognitive behavior therapy for bulimia nervosa, potentially allowing early use of
      a second therapy.

PMID- 10910796
TI  - Relative risk of attention deficits in siblings of patients with schizophrenia.
AB  - OBJECTIVE: Impaired attention has frequently been observed in studies of
      unaffected siblings of patients with schizophrenia. To assess the suitability of
      impaired attention for use as an intermediate phenotype in genetic studies, the
      authors estimated the relative risk of impaired attention in a large group of
      siblings. METHOD: The authors used the Continuous Performance Test, 1-9 version,
      with and without a distraction condition, to study 147 patients with
      schizophrenia, 193 of their siblings, and 47 normal comparison subjects. Relative
      risk (l) was estimated by using cutoff scores that were one, two, and three
      standard deviations below the mean sensitivity index value (d cent) of the normal
      comparison group in both Continuous Performance Test conditions. RESULTS:
      Patients but not their siblings performed worse than the normal comparison
      subjects in both conditions. Fifty percent of the patients, 24% of their
      siblings, and 18% of the normal comparison subjects scored one standard deviation
      below the mean score of the comparison group for the more difficult distraction
      version of the Continuous Performance Test. The patients with Continuous
      Performance Test scores one standard deviation below the mean score of the
      comparison group had a total of 97 siblings. Compared with the comparison group,
      this subgroup of siblings had significantly lower Continuous Performance Test
      scores. Relative risk was also significantly higher for the siblings of patients
      whose scores were one standard deviation (l=2. 1) and two standard deviations
      (l=3.3) below the mean of comparison subjects. Attempts to assess ascertainment
      bias suggest that this may be an underestimate. CONCLUSIONS: Poor performance on
      the Continuous Performance Test appears to be familial and, possibly, genetic.
      Relative risk estimates were in the moderate range. Given the ease of
      administering the Continuous Performance Test, the use of impaired attention as
      an intermediate phenotype could increase the power of genetic studies of
      schizophrenia.

PMID- 10910797
TI  - Randomized controlled trial of the use of compensatory strategies to enhance
      adaptive functioning in outpatients with schizophrenia.
AB  - OBJECTIVE: Cognitive adaptation training is a novel psychosocial treatment
      approach designed to improve adaptive functioning by using compensatory
      strategies in the home or work environment to bypass the cognitive deficits
      associated with schizophrenia. The authors tested the effect of cognitive
      adaptation training on level of adaptive functioning in outpatients with
      schizophrenia. METHOD: Forty-five patients with DSM-IV schizophrenia or
      schizoaffective disorder were randomly assigned for 9 months to one of three
      treatment conditions: 1) standard medication follow-up, 2) standard medication
      follow-up plus cognitive adaptation training, and 3) standard medication follow
      up plus a condition designed to control for therapist time and provide
      environmental changes unrelated to cognitive deficits. Comprehensive assessments
      were conducted every 3 months by raters who were blind to treatment condition.
      RESULTS: Significant differences were found between the three treatment groups in
      levels of psychotic symptoms, motivation, and global functioning at the end of
      the 9-month study period. Patients in the cognitive adaptation training group
      overall had higher levels of improvement, compared with those in the remaining
      treatment conditions. In addition, the three groups had significantly different
      relapse rates over the 9-month study: 13% for the cognitive adaptation training
      group, 69% for the group in which therapist time and environmental changes were
      controlled, and 33% for the group who received standard follow-up only.
      CONCLUSIONS: Compensatory strategies may improve outcomes for patients with
      schizophrenia.

PMID- 10910798
TI  - Cross-sectional study of older outpatients with schizophrenia and healthy
      comparison subjects: no differences in age-related cognitive decline.
AB  - OBJECTIVE: Little is known about the progression of cognitive deficits in older,
      community-dwelling patients with schizophrenia, especially in comparison to
      healthy subjects. METHOD: The authors examined the relationship of age to
      performance on the Mattis Dementia Rating Scale in 116 outpatients with
      schizophrenia and 122 normal comparison subjects. Subjects ranged in age from 40
      to 85 years. RESULTS: Dementia Rating Scale scores were lower in the
      schizophrenia group but correlated negatively with age in both groups, with no
      significant differences seen between the schizophrenia and normal comparison
      groups in slopes that depicted age-related variation. CONCLUSIONS: This cross
      sectional study suggests a relatively stable long-term course of cognitive
      impairment in individuals with schizophrenia, with no evidence of faster
      cognitive decline in outpatients with schizophrenia than in normal comparison
      subjects.

PMID- 10910799
TI  - Heat intolerance in patients with chronic schizophrenia maintained with
      antipsychotic drugs.
AB  - OBJECTIVE: Schizophrenia may be associated with hyperthermic syndromes such as
      febrile catatonia, neuroleptic malignant syndrome, and heatstroke. The authors
      hypothesized that an exercise-heat tolerance test would disclose abnormal
      thermoregulation in schizophrenic patients. METHOD: Seven male schizophrenic
      outpatients in remission maintained on depot antipsychotic treatment and eight
      healthy comparison subjects completed a heat tolerance test that consisted of two
      50-minute bouts of walking a motor-driven treadmill at 40xC (relative
      humidity=40%). RESULTS: A significantly higher rise in rectal and skin
      temperatures was observed in the patient group. No differences in heart rate,
      blood pressure, or perspiration were detected. CONCLUSIONS: Schizophrenic
      patients maintained on antipsychotic drugs exhibit impaired heat tolerance.
      Possible explanations are a reduced ability to convey heat from the body's core
      to the periphery with or without excessive heat production. The hyperthermic
      response to the heat tolerance test may reflect a dysfunction associated with
      schizophrenia, a neuroleptic-induced side effect, or both.

PMID- 10910800
TI  - Novel polymorphism in the gene region encoding the carboxyl-terminal
      intracellular domain of the NMDA receptor 2B subunit: analysis of association
      with schizophrenia.
AB  - OBJECTIVE: N-methyl-D-aspartate (NMDA) receptor antagonists are known to produce
      a syndrome resembling schizophrenia, probably due to their blockade of NMDA
      receptors. The NMDA receptor 2B (NR2B) subunit has been identified as one of the
      major proteins in the postsynaptic density at glutamatergic synapses, suggesting
      that the carboxyl-terminal domain of the NR2B subunit may play a significant role
      in intracellular signal transduction. METHOD: The authors screened for genetic
      variations in the region of the NR2B subunit gene encoding the carboxyl-terminal
      intracellular domain in patients with schizophrenia and studied the association
      between schizophrenia and a novel polymorphism of the NR2B subunit gene. RESULTS:
      One silent mutation (2664C/T) was identified. No significant differences in the
      frequencies of 2664C/T genotypes and alleles were found between patients with
      schizophrenia and healthy comparison subjects. CONCLUSIONS: The findings provided
      no evidence of an association between schizophrenia and the 2664C/T polymorphism
      of the NR2B subunit gene.

PMID- 10910801
TI  - Fluoxetine for bulimia nervosa following poor response to psychotherapy.
AB  - OBJECTIVE: This was an investigation of whether treatment with fluoxetine is
      useful for individuals with bulimia nervosa who do not respond to psychotherapy
      or relapse afterward. METHOD: Twenty-two patients with bulimia nervosa who had
      not responded to, or had relapsed following, a course of cognitive behavior
      therapy or interpersonal psychotherapy were randomly assigned to receive placebo
      (N=9) or fluoxetine (60 mg/day, N=13) for 8 weeks. RESULTS: The median frequency
      of binge eating in the previous 28 days declined from 22 to four episodes in the
      fluoxetine group but increased from 15 to 18 episodes in the placebo group.
      Similarly, purging frequency in the previous 28 days declined from 30 to six
      episodes in the fluoxetine group but increased from 15 to 38 episodes in the
      placebo group. CONCLUSIONS: Fluoxetine may be a useful intervention for patients
      with bulimia nervosa who have not responded adequately to psychological
      treatment.

PMID- 10910802
TI  - Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed
      patients: a double-blind, placebo-controlled study.
AB  - OBJECTIVE: The primary objective of this investigation was to examine the acute
      antidepressant effects of intravenous hydrocortisone and ovine corticotropin
      releasing hormone (CRH) infusions in patients with major depression. METHOD:
      Twenty-two patients who met DSM-III-R criteria for nonpsychotic major depression
      were randomly assigned to receive intravenously 1 mg/kg of ovine CRH, 15 mg of
      hydrocortisone, or saline under double-blind conditions on day 1. Standard
      depression rating scales were completed on day 1 before the study medications
      were administered and again the following day (day 2). RESULTS: Patients treated
      with hydrocortisone demonstrated a significantly greater reduction in total 21
      item Hamilton Depression Rating Scale scores (mean reduction=8.4 points or 37%)
      than patients given ovine CRH (mean=1.2 points) or placebo (mean=1.3 points).
      CONCLUSIONS: Acute hydrocortisone infusion is associated with a rapid and robust
      reduction in depressive symptoms. The authors discuss the therapeutic
      implications of these findings.

PMID- 10910803
TI  - Frequency of anxiety disorders in psychiatric outpatients with major depressive
      disorder.
AB  - OBJECTIVE: The authors determined the frequency of anxiety disorders in a large
      group of depressed outpatients seeking treatment. METHOD: The Structured Clinical
      Interview for DSM-IV was administered to 373 depressed outpatients. RESULTS: More
      than one-half of the patients met the full criteria for a current anxiety
      disorder, and more than one-half of the patients with an anxiety disorder had
      more than one. When partial remissions and anxiety disorder diagnoses classified
      as "not otherwise specified" were included, two-thirds of the patients had a
      current anxiety disorder and three-quarters had a lifetime history of an anxiety
      disorder. CONCLUSIONS: The majority of patients with a principal diagnosis of
      unipolar major depressive disorder have a comorbid anxiety disorder. Because
      antidepressant medications have differential efficacies for anxiety disorders,
      knowledge of the presence of a comorbid anxiety disorder in a depressed patient
      may have treatment implications.

PMID- 10910804
TI  - Irritable bowel syndrome and mirtazapine.

PMID- 10910805
TI  - Quetiapine for treatment-resistant mania.

PMID- 10910806
TI  - Acupuncture and neuropathy.

PMID- 10910807
TI  - Antipsychotics during pregnancy.

PMID- 10910808
TI  - Limbic encephalitis and late-onset psychosis.

PMID- 10910809
TI  - Stressful life events and depression.

PMID- 10910811
TI  - More questions about recovered memories.

PMID- 10910813
TI  - More questions about recovered memories.

PMID- 10910814
TI  - More questions about recovered memories.

PMID- 10910815
TI  - More questions about recovered memories.

PMID- 10910816
TI  - Dr. Chu replies

PMID- 10910817
TI  - More questions about recovered memories.

PMID- 10910827
TI  - A strategy to improve endobronchial drug administration.

PMID- 10910828
TI  - Plasma aprotinin concentrations during cardiac surgery: full- versus half-dose
      regimens.
AB  - Aprotinin is an effective but expensive drug used during cardiac surgery to
      reduce blood loss and transfusion requirements. Currently, aprotinin is
      administered to adults according to a fixed protocol regardless of the patient's
      weight. The purpose of this study was to determine aprotinin levels in patients
      receiving full- and half-dose aprotinin regimens by a simple functional aprotinin
      assay and to design a more individualized aprotinin dosage regimen for cardiac
      surgical patients. The mean plasma aprotinin concentration peaked 5 min after the
      initiation of cardiopulmonary bypass (full 401 +/- 92 KIU/mL, half 226 +/- 56
      KIU/mL). The mean plasma aprotinin concentration after 60 min on cardiopulmonary
      bypass was less (full 236 +/- 81 KIU/mL, half 160 +/- 63 KIU/mL). There was large
      variation in the aprotinin concentration among patients. A statistically
      significant correlation was found between aprotinin concentration and patient
      weight (r(2) = 0.67, P < 0.05). IMPLICATIONS: The current dosing schedule for
      aprotinin results in a large variation in aprotinin plasma concentrations among
      patients and a large variation within each patient over time. We combined the
      information provided by our study with that of a previous pharmacokinetic study
      to develop a potentially improved, weight-based, dosing regime for aprotinin.

PMID- 10910829
TI  - Elimination of recombinant hirudin by modified ultrafiltration during simulated
      cardiopulmonary bypass: assessment of different filter systems.
AB  - Recombinant hirudin (r-hirudin) is being used increasingly in patients with
      heparin-induced thrombocytopenia type II. Renal failure has been demonstrated to
      prolong the half-life of r-hirudin and to cause bleeding in patients who have
      undergone cardiopulmonary bypass (CPB). We assessed the ability of different
      filter systems for modified ultrafiltration to eliminate r-hirudin in vitro using
      simulated CPB. r-Hirudin concentration was measured (chromogenic laboratory
      standard plus ecarin clotting time) before and after filtration, and its
      elimination was calculated using both controlled system flow and arterial inflow
      (separate pump). Four hemofilters (Renoflow II, Baxter; Arylane H4, Cobe;
      Ultraflux AV 600, Fresenius; and BCS 110 Plus, Iostra) and two plasmapheresis
      filter systems (ASAHI Plasmaflow OP, Diamed; and PF 2000 N, Gambro) were assessed
      (5 filters of each brand = 30 filters) in a closed in vitro CPB system applying
      conditions usually occurring during CPB. Ten plasmapheresis filters showed a
      greater ability than 20 hemofilters to eliminate r-hirudin (60%-70% vs 15%-42%)
      within the shortest time (80 vs 180 s). Among the four hemofilter systems, the
      Arylane H4 filter provided the most effective (42%) r-hirudin elimination.
      Elimination of r-hirudin was markedly improved using plasmapheresis systems,
      compared with hemofilter systems. Our findings may be relevant to patients with
      impaired renal function, who have been administered r-hirudin during CPB.
      IMPLICATIONS: Modified ultrafiltration may enhance the elimination of recombinant
      hirudin, although plasmapheresis systems provide the most rapid and complete
      elimination of recombinant-hirudin during simulated cardiopulmonary bypass. The
      decision to use a specific system will ultimately depend on the prevailing
      clinical situation and overall health of the patient.

PMID- 10910830
TI  - Myocardial dysfunction associated with proinflammatory cytokines after esophageal
      resection.
AB  - Proinflammatory cytokines have been implicated in mediating myocardial
      dysfunction associated with major surgery. We investigated the profile of
      proinflammatory cytokines and the association of cytokine levels with myocardial
      function after esophagectomy. We studied 12 patients who underwent subtotal
      esophagectomy. One patient died of multiple organ failure. This patient had the
      largest interleukin-6 (IL-6) level of all the subjects. IL-6 levels increased
      from 14.9 +/- 8.7 pg/mL to 498.4 +/- 294.3 pg/mL (P < 0.05) at 6 h
      postoperatively. Interleukin-8 (IL-8) levels also significantly increased
      postoperatively. Right ventricular ejection fraction (RVEF) decreased from 44% +/
      1% to 36% +/- 2% (P < 0.05) and 37% +/- 2% (P < 0.05) at 6 h and 12 h
      postoperatively. Stroke volume index (SVI) decreased significantly at the end of
      operation and at 6 h and 12 h postoperatively. The changes of RVEF and SVI showed
      an independent negative correlation with the IL-6 level (r = -0.70, P < 0.001 and
      r = -0.62, P < 0.001, respectively). In contrast, the change of RVEF and SVI was
      not correlated with the IL-8 level. Esophagectomy is associated with transient
      depression of myocardial function. IL-6 may contribute to this postoperative
      myocardial dysfunction. IMPLICATIONS: We examined the association between
      myocardial function and proinflammatory cytokines after esophagectomy.
      Interleukin-6 may be the cytokine that most sensitively reflects the
      postoperative myocardial dysfunction.

PMID- 10910831
TI  - The concentration-dependent effects of propofol on rat ventricular myocytes.
AB  - Whether propofol contributes a direct negative inotropic effect is controversial.
      Our principal aim in this study was to determine whether negative inotropic
      effects of propofol occur at clinically relevant concentrations. We constructed
      the concentration-response relationship for the negative inotropic effects on
      intact, isolated, stimulated rat ventricular myocytes. Contraction was measured
      as cell shortening by using an optical system. Propofol was applied as dilutions
      of the commercial preparation in physiological saline solution. The drug vehicle
      had a minimal effect on myocyte contractility. Propofol produced a concentration
      dependent reduction in evoked contraction at concentrations greater than 5
      microM. The maximum effect was observed at >100 microM, with the K(0.5)
      calculated to be 34.5 microM (95% CI, 21.8-54.7 microM). In further experiments,
      we investigated the relationship between changes in contractility and changes in
      Ca(2+) transient (measured by using fura-2 fluorescence) after the application of
      propofol. By using the shift in the relationship of the cell length to fura-2
      fluorescence ratio in the relaxation phase of a contraction as an index of Ca(2+)
      response of the myofilaments, we demonstrated that some of the negative inotropic
      effect of propofol may be caused by a reduction in myofilament Ca(2+)
      sensitivity. We confirmed this by comparing the reduction in contractility in the
      presence of propofol with that caused by reducing the extracellular Ca(2+)
      concentration. We observed that, for a decrease in the fura-2 fluorescence ratio
      of 21%, propofol caused a 12% (95% CI, 2% to 22%) greater reduction in
      contractility than predicted from reducing the extracellular Ca(2+)
      concentration. However, the K(0.5) for the negative inotropic effect of propofol
      we observed is more than 80 times the 50% effective concentration value for
      anesthesia. The potential relevance of these findings for clinical use of
      propofol in humans is discussed. IMPLICATIONS: By using intact, isolated rat
      heart ventricle cells, we investigated the mechanisms and concentration
      dependence of the depressant effect of propofol on contractility of the heart. We
      conclude that direct effects of propofol on the heart are unlikely to be of
      significance at the clinical dosage usually given.

PMID- 10910833
TI  - Severe incisional pain and long thoracic nerve injury after port-access minimally
      invasive mitral valve surgery.
AB  - The authors describe the occurrence of severe postoperative pain and long
      thoracic nerve injury after Port-Access minimally invasive mitral valve surgery.
      The potential for these events and the impact on postoperative hospitalization
      and rehabilitation are emphasized.

PMID- 10910832
TI  - Fast-track cardiac anesthesia: use of remifentanil combined with intrathecal
      morphine as an alternative to sufentanil during desflurane anesthesia.
AB  - The purpose of this cardiac fast-track study was to evaluate the use of
      remifentanil (R) combined with intrathecal (IT) morphine as an alternative to
      sufentanil (S) during desflurane anesthesia with respect to postoperative pain
      control. Prior to entering the operating room, patients in the R group (n = 20)
      received morphine, 8 microg/kg IT. Anesthesia was induced using a standardized
      anesthetic technique in all patients. In the R group, anesthesia was maintained
      with R, 0.1 microg. kg(-1). min(-1) in combination with desflurane 3-10%. In the
      S group (n = 20), patients received S 0.3 microg. kg(-1). h(-1) and desflurane 3
      10%. There were no differences between the two groups with respect to time from
      arrival in the intensive care unit to tracheal extubation (5.1 +/- 4.3 h vs 5.8
      +/- 6.7 h for R and S groups, respectively). After extubation, patients in the R
      group had significantly lower visual analog pain scores, reduced patient
      controlled analgesic requirements, and greater satisfaction with their
      perioperative pain management, compared with patients in the S group. We conclude
      that R combined with IT morphine provided superior pain control after cardiac
      surgery compared with a S-based general anesthetic technique. IMPLICATIONS: As
      part of a cardiac fast-tracking program involving desflurane anesthesia, the use
      of intrathecal morphine in combination with a remifentanil infusion provided
      improved postoperative pain control, compared with IV sufentanil alone.

PMID- 10910834
TI  - Intraoperative use of inhaled PGI(2) for acute pulmonary hypertension and right
      ventricular failure.
AB  - Inhaled prostacyclin (PGI(2)) can be used as an effective pulmonary vasodilator
      intraoperatively to treat pulmonary hypertension and impending right ventricular
      failure.

PMID- 10910835
TI  - Pulmonary thromboembolism during liver transplantation: possible association with
      antifibrinolytic drugs and novel treatment options.
AB  - The authors describe two cases of massive intraoperative pulmonary
      thromboembolism resulting in cardiovascular collapse during liver
      transplantation. The potential role of antifibrinolytic drugs is discussed, along
      with the use of treatment modalities not previously applied in this setting.

PMID- 10910836
TI  - Congenital tracheal bronchus: the inability to isolate the right lung with a
      univent bronchial blocker tube.
AB  - Tracheal bronchus is a congenital anomaly in which the right upper lobe bronchus
      originates from the lateral tracheal wall. This anatomic variant is reported in
      approximately 1 of 250 patients at bronchoscopy. Although it is usually of little
      clinical significance, this atypical origin of the right upper lobe bronchus may
      complicate one-lung ventilation during thoracic surgery.

PMID- 10910837
TI  - Safe and cost-effective preoperative preparation of patients with
      pheochromocytoma.
AB  - This study examines the management of patients diagnosed with pheochromocytoma at
      a major academic teaching hospital. The findings indicate that most patients can
      be safely managed as outpatients preoperatively, resulting in significantly
      shorter hospitalizations and no adverse sequelae.

PMID- 10910838
TI  - The awakening concentration of sevoflurane in children.
AB  - Sevoflurane is frequently used as a rapidly acting drug for the induction of
      anesthesia. We investigated the awakening concentration (MAC-awake) of
      sevoflurane in ASA physical status I children (age range 2-10 yr). We also
      investigated the effects of two different doses of clonidine (2 and 4 microg/kg)
      on the MAC-awake of sevoflurane. Subjects were randomly divided into three groups
      and received placebo (n = 24), clonidine 2 microg/kg (n = 17), or clonidine 4
      microg/kg (n = 22) orally, 100 min before the induction of anesthesia. Sedation
      scores were estimated, by using a five-point scale, after entry into the
      operating room, and anesthesia was induced and maintained with sevoflurane in
      oxygen and balanced nitrogen, without an additional anesthetic. After surgery,
      end-tidal sevoflurane was decreased stepwise by 0.2% at 15-min intervals, a
      standardized verbal command was played to the patients, and the MAC-awake was
      determined. The MAC-awake of sevoflurane alone was 0. 78% +/- 0.24% (mean +/-
      SD), which decreased to 0.36% +/- 0.09% and 0.36% +/- 0.16% (both P <0.0001,
      compared with the control group) after premedication with the small and large
      doses of clonidine, respectively. The lack of any dose-response relationship
      might be explained by a plateau effect. IMPLICATIONS: The awakening concentration
      of sevoflurane in unpremedicated children was 0.78%. Oral clonidine premedication
      at a dose of 2 microg/kg reduced the awakening concentration to 0.36%. However,
      an additional decrease in this value was not observed after the administration of
      the larger dose of clonidine premedication (4 microg/kg).

PMID- 10910839
TI  - Propionic acidemia in a four-month-old male: a case study and anesthetic
      implications.
AB  - Propionic acidemia is a rare genetic disease associated with significant medical
      problems. When patients with this disease present for surgery, their anesthetic
      must be tailored to meet their special needs. This case report provides
      information regarding propionic acidemia and its anesthetic management.

PMID- 10910840
TI  - Is succinylcholine after pretreatment with d-tubocurarine and lidocaine
      contraindicated for outpatient anesthesia?
AB  - Because succinylcholine has obvious advantages for facilitating endotracheal
      intubation in the ambulatory setting (e.g., low cost, fast onset, and no need for
      reversal of neuromuscular block), it is important to determine whether this
      muscle relaxant is indeed associated with an increased incidence of postoperative
      myalgias, compared with alternative but more expensive nondepolarizing muscle
      relaxants. We studied 119 outpatients undergoing endoscopic nasal sinus surgery
      or septoplasty. The anesthetic technique consisted of propofol/lidocaine for
      induction, followed by isoflurane/nitrous oxide/oxygen for maintenance. Oral
      tracheal intubation was performed by using a fiberscope. Patients were randomly
      assigned to one of two muscle relaxant groups. Group 1 patients received d
      tubocurarine 3 mg followed by succinylcholine 1.5 mg/kg. Group 2 patients
      received mivacurium 0.2 mg/kg. After recovery from anesthesia, patients were
      asked whether they had any muscle pain and/or stiffness. Pain was categorized by
      location and quantified by using a verbal scale (from 0 to 10). Analgesic usage
      and myalgias limiting ambulation were recorded. After discharge from the
      ambulatory surgery unit, patients were contacted by telephone on Postoperative
      Day 1. If patients complained of myalgias, they were contacted by telephone on
      Days 2 and 3. Only one patient (in the mivacurium-treated group) reported myalgia
      as a limiting factor in ambulation or resumption of normal activity. There were
      no differences between groups with respect to the incidence (21% in the
      succinylcholine-treated group and 18% in the mivacurium-treated group), location,
      or severity of myalgia. In conclusion, succinylcholine (preceded by pretreatment
      with d-tubocurarine and lidocaine) is not associated with an increased incidence
      of myalgias, compared with mivacurium, when used to facilitate tracheal
      intubation in patients undergoing ambulatory nasal surgery. IMPLICATIONS: The
      results of this study show that the frequency of muscle pains after surgery in
      outpatients is approximately 20%, regardless of whether succinylcholine (after
      precurarization) or mivacurium is used to assist in insertion of the breathing
      tube.

PMID- 10910841
TI  - A comparison of distilled water and normal saline as diluents for endobronchial
      administration of epinephrine in the dog.
AB  - We compared the effects of distilled water and normal saline as diluents for the
      endobronchial administration of epinephrine in anesthetized dogs by using a cross
      over design. Six dogs received 2 mL of either normal saline or distilled water
      into the bronchus, and the other solution was administered 1 wk later. Eight dogs
      received 0.02 mg/kg epinephrine diluted in either distilled water (E + water) or
      normal saline (E + saline) to a total volume of 2 mL into the bronchus, and the
      other solution was administered 1 wk later. Normal saline or distilled water
      without epinephrine did not affect the plasma epinephrine concentration, mean
      arterial pressure (MAP), and PaO(2). The peak plasma epinephrine concentration
      was significantly larger after treatment with E + water (26.5 +/- 7.9 ng/mL) than
      after E + saline (2.1 +/- 0.7 ng/mL). E + water caused an increase in MAP of 91
      +/- 24 mm Hg, whereas E + saline did not affect MAP. The maximal decrease in
      PaO(2) after the administration of E + water (14 +/- 5 mm Hg) was significantly
      greater than after E + saline (7 +/- 2 mm Hg). In conclusion, distilled water as
      the diluent for endobronchially administered epinephrine to a total volume of 2
      mL allowed better absorption of epinephrine compared with normal saline without a
      serious detrimental effect on PaO(2). IMPLICATIONS: Using a small volume of
      distilled water as the diluent for endobronchial epinephrine administration
      significantly increased epinephrine absorption and arterial pressure in
      comparison with normal saline, without having a serious detrimental effect on
      PaO(2), in an anesthetized, noncardiopulmonary, resuscitation dog model.

PMID- 10910842
TI  - Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered
      acetylcholine receptor expression.
AB  - Large doses of glucocorticoids can alter muscle physiology and susceptibility to
      neuromuscular blocking drugs by mechanisms not clearly understood. We
      investigated the effects of moderate and large doses of prednisolone on muscle
      function and pharmacology, and their relationship to changes in muscle size and
      acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague
      Dawley rats were randomly allocated to receive daily subcutaneous doses of 10
      mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal
      volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food
      restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked
      peak twitch tensions, tetanic tensions, and fatigability, and the dose-response
      curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo
      and related to muscle mass or expression of AChRs. Rate of body weight gain was
      depressed in the P100, FR, and P10 groups compared with the S group. Tibialis
      muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked
      peak twitch and tetanic tensions were less in the P100 group than in the P10 or S
      groups, however, tension per milligram of muscle mass was greater in the P100
      group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg)
      in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9
      +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10
      group than in the S group. The evoked tensions correlated with muscle mass (r(2)
      = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose
      of d-tubocurarine did not correlate with muscle mass or AChR expression. Our
      results suggest that the neuromuscular dysfunction after prednisolone is dose
      dependent, and derives primarily from muscle atrophy and derives less so from
      changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic
      glucocorticoid therapy alters neuromuscular physiology and pharmacology are
      unclear. We suggest that the observed effects are dose-dependent and derive
      primarily from muscle atrophy and derive less from changes in acetylcholine
      receptor expression.

PMID- 10910843
TI  - Could heart rate variability analysis become an early predictor of imminent brain
      death? A pilot study.
AB  - Physiology of brain death is characterized by major disturbances of autonomic
      nervous system (ANS) activity which can lead to graft dysfunction. These findings
      exhibit the importance of early diagnosis of brain death to improve
      transplantation outcome. The aim of this prospective study was to assess whether
      heart rate variability (HRV) analysis, a noninvasive method to investigate ANS
      activity in comatose patients, could achieve this goal. A total of 14 brain
      injured patients were included in the study as soon as they exhibited the
      clinical signs of imminent brain death. The electrocardiogram was then recorded
      from two leads with a Holter digital monitor. The clinical diagnosis of brain
      death was considered after an autonomic storm had occurred. HRV was assessed from
      6 h before to 6 h after brain death in both time domain and spectral analysis,
      estimating either global ANS activity (index of variability, total power),
      parasympathetic activity (percentage of delta of R-R interval >50 ms, root mean
      square for successive interval differences, LnHF) or sympathetic activity (LnLF).
      Hourly averages of these variables were compared by using one-way analysis of
      variance. To assess whether HRV could per se diagnose brain death, receiver
      operating characteristic curves were generated for total power, root mean square
      for successive interval differences, and LnHF. We observed, for 6 h before brain
      death, a progressive extinction of the influence of the ANS on cardiovascular
      regulation. There was no activity in the two components of the ANS as soon as
      brain death occurred. HRV analysis appeared to be a very sensitive but a less
      specific method of diagnosing brain death. IMPLICATIONS: A total of 14 brain
      injured patients with the clinical criteria of imminent brain death were enrolled
      for electrocardiogram recording and heart rate variability analysis (a
      noninvasive method to investigate autonomic nervous system activity). For 6 h
      before brain death, we observed a progressive extinction of autonomic nervous
      system activity which was not present as soon as brain death was clinically
      evoked.

PMID- 10910844
TI  - Economic analysis of linking operating room scheduling and hospital material
      management information systems for just-in-time inventory control.
AB  - Operating room (OR) scheduling information systems can decrease perioperative
      labor costs. Material management information systems can decrease perioperative
      inventory costs. We used computer simulation to investigate whether using the OR
      schedule to trigger purchasing of perioperative supplies is likely to further
      decrease perioperative inventory costs, as compared with using sophisticated,
      stand-alone material management inventory control. Although we designed the
      simulations to favor financially linking the information systems, we found that
      this strategy would be expected to decrease inventory costs substantively only
      for items of high price ($1000 each) and volume (>1000 used each year). Because
      expensive items typically have different models and sizes, each of which is used
      by a hospital less often than this, for almost all items there will be no benefit
      to making daily adjustments to the order volume based on booked cases. We
      conclude that, in a hospital with a sophisticated material management information
      system, OR managers will probably achieve greater cost reductions from focusing
      on negotiating less expensive purchase prices for items than on trying to link
      the OR information system with the hospital's material management information
      system to achieve just-in-time inventory control. IMPLICATIONS: In a hospital
      with a sophisticated material management information system, operating room
      managers will probably achieve greater cost reductions from focusing on
      negotiating less expensive purchase prices for items than on trying to link the
      operating room information system with the hospital's material management
      information system to achieve just-in-time inventory control.

PMID- 10910845
TI  - Postoperative death and malpractice suits: is autopsy useful?
AB  - This report demonstrates the extremely high yield of autopsies performed in the
      case of postoperative death with suspicion of malpractice. They frequently
      identified undetected complications. They could also suggest faulty or negligent
      practice that would otherwise go unrecognized. This report supports the
      widespread use of autopsies to investigate perioperative death.

PMID- 10910846
TI  - The effect of calcium channel blockers on cerebral oxygenation during tracheal
      extubation.
AB  - Calcium channel blockers are effective in stabilizing systemic hemodynamics
      during tracheal extubation. However, they may increase cerebral blood flow (CBF)
      during tracheal extubation because of cerebral vasodilation, even if systemic
      arterial blood pressure decreases. In this study, we observed changes in cerebral
      oxygenation during tracheal extubation by using near-infrared spectroscopy and
      evaluated the effect of nicardipine and diltiazem on the resultant changes. We
      studied 45 women undergoing elective gynecologic surgery. After surgery, the
      patients were randomly allocated to three groups (n = 15 each): saline (control),
      0.02 mg/kg nicardipine, and 0.2 mg/kg diltiazem. After 2 min, we started to
      aspirate secretions for 2 min and then, extubated the trachea. Changes in
      cerebral oxygenated hemoglobin (HbO(2)) and deoxygenated hemoglobin were measured
      during the extubation procedure for 9 min after drug treatment. Systemic
      hemodynamics, including mean arterial blood pressure, heart rate, end-tidal
      CO(2), end-tidal sevoflurane concentration, and peripheral arterial oxygen
      saturation were also monitored. During extubation, HbO(2) increased
      significantly, presumably caused by the increase in CBF. Changes in deoxygenated
      hemoglobin were minimal. Compared with the control, nicardipine and diltiazem
      significantly inhibited the increase in mean arterial blood pressure. On the
      contrary, they significantly enhanced the increase in HbO(2). In conclusion,
      calcium channel blockers may increase CBF during extubation, even if these drugs
      stabilize systemic hemodynamics. IMPLICATIONS: This study is a preliminary report
      evaluating the changes in cerebral oxygenation during the tracheal extubation.
      Cerebral oxygenated hemoglobin increased significantly, presumably caused by the
      increase in cerebral blood flow during extubation. In addition, these changes
      were enhanced by calcium channel blockers.

PMID- 10910847
TI  - A correlation between dexmedetomidine-induced biphasic increases in free
      cytosolic calcium concentration and energy metabolism in astrocytes.
AB  - The alpha(2)-adrenergic agonist, dexmedetomidine, increases free cytosolic
      calcium concentration ([Ca(2+)](i)) in astrocytes, but not in neurons. The
      present study was performed to characterize the origin of the increased Ca(2+) in
      mouse astrocytes cultured from the cerebral cortex, the dose dependence of the
      effect, and its functional consequences. The increase in [Ca(2+)](i) was
      independent of extracellular Ca(2+), but was inhibited by dantrolene, showing
      that it is derived from intracellular stores; two peaks in [Ca(2+)](i) were
      demonstrated-one around 100 nM dexmedetomidine and the other in the low
      micromolar range. A similar dose dependence was found for pyruvate
      dehydrogenation, the initial metabolic reaction of oxidative degradation of
      pyruvate, suggesting that the these events are interrelated. The alpha(2)
      adrenergic antagonist, yohimbine, abolished the metabolic stimulation at both
      peaks. However, whereas the increase in [Ca(2+)] (i) at 100 nM is abolished by
      yohimbine, increase in the micromolar range was partly inhibited by yohimbine and
      partly by idazoxan, an inhibitor at the imidazoline-preferring site. The
      stimulation of energy metabolism in cerebrocortical astrocytes may explain the
      repeated finding that dexmedetomidine does not decrease oxidative metabolism in
      the brain in vivo. The functional importance of the additional imidazoline
      receptor-mediated increase in [Ca(2+)](i) at large dexmedetomidine concentrations
      is unknown. IMPLICATIONS: Cytosolic calcium concentration and metabolism were
      measured in cultured astrocytes, the predominant glial cells. The results suggest
      that dexmedetomidine may owe its anesthetic effects to a Ca(2+)-dependent
      increase in astrocytic energy metabolism, allowing these cells to more
      effectively remove extracellular glutamate and potassium ions, and thus,
      decreasing neuronal excitability.

PMID- 10910848
TI  - A randomized, double-blinded comparison of ondansetron, droperidol, and placebo
      for prevention of postoperative nausea and vomiting after supratentorial
      craniotomy.
AB  - Nausea or vomiting occurs frequently after craniotomy. Because of the need for
      frequent postoperative neurological assessment, an effective antiemetic with
      minimal sedative side effects is needed. Therefore, we compared ondansetron to
      droperidol in a randomized, double-blinded, placebo-controlled study. A total of
      60 adults requiring elective supratentorial craniotomy received standardized IV
      anesthesia with 4 mg of ondansetron, 0.625 mg of droperidol, or placebo at skin
      closure. The incidence of postoperative nausea, emesis, pain and sedation scores,
      and rescue antiemetic use were recorded at 0, 0.5, 1, 4, 8, 12, 24, and 48 h. All
      groups were demographically similar. Differences existed for cumulative 8, 12,
      and 24 h incidences of nausea (24 h, P = 0.03) and emesis (24 h, P = 0.04).
      Within 4 h, when maximal effect could be expected from treatment, 20% of the
      ondansetron group, 25% of the droperidol group and 50% of the placebo group
      received rescue antiemetic (P = 0.12). No differences in pain (P = 0.82) or
      sedation (P = 0.74) scores were detected. Both ondansetron and droperidol prevent
      nausea; however, only droperidol reduces emesis after supratentorial craniotomy.
      The dose of droperidol used was not more sedating than ondansetron. Sustained
      reduction in nausea and emesis over 24 h indicates a preemptive benefit of
      prophylactic antiemetic in this surgical population. IMPLICATIONS: Nausea and
      vomiting after brain surgery are particularly troubling, because effective
      treatment may cause sedation, making postoperative neurological assessment
      difficult. Our study shows that both ondansetron and droperidol are effective in
      reducing nausea, and that droperidol is particularly effective in reducing
      vomiting. Neither drug caused more sedation than placebo.

PMID- 10910849
TI  - Concentrations of lidocaine and monoethylglycine xylidide in brain, cerebrospinal
      fluid, and plasma during lidocaine-induced epileptiform electroencephalogram
      activity in rabbits: the effects of epinephrine and hypocapnia.
AB  - When injecting lidocaine into tissues, the mean toxic dose of lidocaine may be
      increased by adding epinephrine to lidocaine and by decreasing the PaCO(2). In
      contrast, when lidocaine is introduced directly into an artery or vein, adding
      epinephrine to lidocaine may decrease the mean toxic dose of lidocaine. Less is
      known about the effects of decreased PaCO(2) on intravascular lidocaine toxicity.
      We infused lidocaine in 24 rabbits at 4 mg. kg(-1). min(-1) with/without
      epinephrine and with/without hypocapnia. We measured the time to onset of
      lidocaine-induced seizures, total dose of lidocaine at the time of seizures, and
      concentrations of lidocaine and monoethylglycine xylidide (MEGX), a metabolite of
      lidocaine, in plasma, brain, and cerebrospinal fluid. Epinephrine decreased onset
      time by 11% with hypocapnia and by 21% with normocapnia, and it increased plasma
      MEGX by 1 microg/mL with hypocapnia and 2 microg/mL with normocapnia. Hypocapnia
      increased onset time by 18% without epinephrine and by 33% with epinephrine, and
      it increased whole-brain MEGX by 10 microg/mL without epinephrine and by 14
      microg/mL with epinephrine. We conclude that, when lidocaine is given
      intravascularly, hypocapnia increases onset time and lidocaine dose required for
      seizures. These effects occur with no change in the concentration of lidocaine in
      plasma or the brain. IMPLICATIONS: Hypocapnia increases the toxic dose of
      lidocaine given IV without altering lidocaine concentrations in blood, brain, or
      cerebrospinal fluid. Whole-brain monoethylglycine xylidide concentration is
      greater during hypocapnia than during normocapnia, and the addition of
      epinephrine to lidocaine increases the concentration of monoethylglycine xylidide
      in plasma.

PMID- 10910850
TI  - Informed consent for obstetric anesthesia research: factors that influence
      parturients' decisions to participate.
AB  - Patients who are approached to participate in clinical studies just before
      delivery may have insufficient time to make an informed decision and/or may feel
      pressured into participation. This study was designed to examine factors that
      influence parturients to consent or decline participation in an anesthesia study
      related to their delivery. Parturients who had been approached to participate in
      a continuing clinical obstetric anesthesia study were subsequently given a
      questionnaire that documented their reasons for consenting or declining
      participation. There were no demographic differences among the consenters (n =
      166) and nonconsenters (n = 109). The most important factors in the patient's
      decision to consent were related to their understanding and perceived importance
      of the study and the potential benefit to other women. Forty-one (40. 6%)
      nonconsenters strongly considered their pain/discomfort a factor in declining
      participation. Only one patient felt some pressure to consent, suggesting that
      the overall environment was noncoercive. Logistic regression analysis
      demonstrated that patients who read the consent form completely, those who had
      participated in a previous research study, and those who were less anxious about
      participating were more likely to consent. IMPLICATIONS: Obtaining informed
      consent for obstetric anesthesia studies presents a challenge to the
      anesthesiologist. Results from this study suggest that the environment in which
      consent for obstetric studies is sought is not coercive. However, it is important
      that the anesthesiologist ensures that the patient fully understands the study
      and develops a rapport with the patient to allay any anxiety associated with her
      participation as a potential research subject.

PMID- 10910851
TI  - Comparison of epidural fentanyl versus epidural sufentanil for analgesia in
      ambulatory patients in early labor.
AB  - Epidural sufentanil, after a lidocaine and epinephrine test dose, provides
      adequate analgesia and allows for ambulation during early labor. Epidural
      fentanyl has not been evaluated in this setting. The current study was designed
      to determine whether there is an analgesic difference between epidural fentanyl
      and epidural sufentanil in laboring patients. Forty-six laboring nulliparous
      women, at <5-cm cervical dilation, who requested epidural analgesia were
      enrolled. After a 3-mL test dose of lidocaine with epinephrine, patients were
      randomized to receive either sufentanil 20 microg or fentanyl 100 microg. After
      administration of the analgesic, pain scores and side effects were recorded for
      each patient at 5, 10, 15, 20, and 30 min and every 30 min thereafter, by an
      observer blinded to the technique used. There were no demographic differences
      between the two groups. Pain relief was rapid for all patients. The mean
      durations of analgesia were similar between the sufentanil group (138 +/- 50 min)
      and the fentanyl group (124 +/- 42 min). Side effects were similar between the
      two groups. In early laboring patients, epidural fentanyl 100 microg, after a
      lidocaine and epinephrine test dose, provides analgesia comparable to that of
      sufentanil 20 microg. IMPLICATIONS: In early laboring patients, epidural fentanyl
      100 microg, after a lidocaine and epinephrine test dose, provides analgesia
      comparable to that of sufentanil 20 microg.

PMID- 10910852
TI  - Brachial plexus anesthesia with verapamil and/or morphine.
AB  - Calcium channel blockers potentiate the analgesic properties of both local
      anesthetics and opioids. We examined the analgesic effects of administering
      morphine, verapamil, or its combination into the brachial plexus sheath with
      lidocaine in 75 patients undergoing upper extremity orthopedic surgery. All
      patients received brachial plexus anesthesia with 40 mL of 1.5% lidocaine and
      epinephrine 5 microg/mL. In addition, patients were randomized to 1 of 5 groups:
      Group 1 received IV saline; Group 2 received IV verapamil 2.5 mg and morphine 5
      mg; Group 3 received IV verapamil 2.5 mg and morphine 5 mg was added to the
      lidocaine solution; Group 4 received IV morphine 5 mg and verapamil 2.5 mg was
      added to the lidocaine solution; and Group 5 received verapamil 2.5 mg and
      morphine 5 mg were added to the lidocaine solution. Postoperatively, patients
      rated their pain (0-10) at 1, 6, 12, and 24 h. Patients were instructed to take 1
      acetaminophen 325 mg/oxycodone 5 mg tablet every 3 h whenever the pain score
      exceeded 3. Analgesic duration was significantly increased in those patients
      receiving brachial plexus blocks with morphine (Groups 3 and 5) (P < 0.005). The
      total 24 h acetaminophen/oxycodone use was also less in Groups 3 and 5 (P < 0.
      03). Duration of anesthesia (time of abolition of pinprick response) was
      significantly increased in those patients receiving brachial plexus blocks with
      verapamil (Groups 4 and 5) (P = 0.002). We conclude that the addition of
      verapamil to brachial plexus block with lidocaine can prolong the duration of
      sensory anesthesia, but it had no effect on analgesic duration of 24 h analgesic
      use. IMPLICATIONS: The addition of verapamil to brachial plexus block with
      lidocaine and morphine prolongs the duration of sensory anesthesia, but has no
      effect on analgesic duration or 24 h analgesic use.

PMID- 10910853
TI  - Fentanyl improves analgesia but prolongs the onset of axillary brachial plexus
      block by peripheral mechanism.
AB  - We evaluated the effects of fentanyl added to lidocaine for axillary brachial
      plexus block in 66 adult patients scheduled for elective hand and forearm
      surgery. In this double-blinded study, all patients received 40 mL of 1.5%
      lidocaine with 1:200,000 epinephrine, injected into the brachial plexus sheath
      using the axillary perivascular technique, and they were randomized into three
      groups. Group 1 was given lidocaine containing 2 mL of normal saline plus 2 mL of
      normal saline IV. Patients in Group 2 received lidocaine containing 100 microg
      fentanyl plus 2 mL of normal saline IV. Group 3 patients received lidocaine
      containing 2 mL of normal saline plus 100 microg fentanyl IV. Sensory and motor
      blockade were evaluated by using a pinprick technique and by measuring the
      gripping force, respectively. The success rate of sensory blockade for radial and
      musculocutaneous nerves and the duration of the sensory blockade significantly
      increased in Group 2 (323 +/- 96 min) as compared with Group 1 (250 +/- 79 min).
      However, onset time of analgesia was prolonged in every nerve distribution by
      adding fentanyl to brachial plexus block. IV fentanyl had no effect on the
      success rate, onset, or duration of blockade. We conclude that the addition of
      fentanyl to lidocaine causes an improved success rate of sensory blockade but a
      delayed onset of analgesia, although this may be accounted for by the decreased
      pH caused by the fentanyl. IMPLICATIONS: It is still unclear whether the addition
      of a peripheral opioid is useful for nerve blockade in humans. Peripheral
      application of fentanyl to lidocaine for axillary brachial plexus blockade in
      this study provided an improved success rate of sensory blockade and prolonged
      duration.

PMID- 10910854
TI  - Small-dose clonidine prolongs postoperative analgesia after sciatic-femoral nerve
      block with 0.75% ropivacaine for foot surgery.
AB  - To evaluate the effects of adding small-dose clonidine to 0.75% ropivacaine
      during peripheral nerve blocks, 30 ASA physical status I and II patients
      undergoing hallux valgus repair under combined sciatic-femoral nerve block were
      randomly allocated in a double-blinded fashion to receive block placement with 30
      mL of either 0.75% ropivacaine alone (group Ropivacaine, n = 15) or 0.75%
      ropivacaine plus 1 microg/kg clonidine (group Ropivacaine-Clonidine, n = 15).
      Hemodynamic variables, oxygen saturation, and levels of sedation, as well as the
      time required to achieve surgical block and time to first analgesic request, were
      recorded by a blinded observer. Time to surgical blockade required 10 min in both
      groups. Patients in the Ropivacaine-Clonidine group were more sedated than
      patients in the Ropivacaine group only 10 min after block placement. No
      differences in oxygen saturation and hemodynamic variables, degree of pain
      measured at first analgesic request, and consumption of postoperative analgesics
      were observed between the two groups. The mean time from block placement to first
      request for pain medication was shorter in group Ropivacaine (13.7 h; 25th-75th
      percentiles: 11. 8-14.5 h) than in group Ropivacaine-Clonidine (16.8 h; 25th-75th
      percentiles: 13.5-17.8 h) (P = 0.038). We conclude that adding 1 microg/kg
      clonidine to 0.75% ropivacaine provided a 3-h delay in first request for pain
      medication after hallux valgus repair, with no clinically relevant side effects.
      IMPLICATIONS: This prospective, randomized, double-blinded study demonstrated
      that, when providing combined sciatic-femoral nerve block for hallux valgus
      repair, the addition of 1 microg/kg clonidine to 0.75% ropivacaine prolongs the
      duration of postoperative analgesia by 3 h, with only a slight and short-lived
      increase in the degree of sedation and no hemodynamic adverse effects.

PMID- 10910855
TI  - The efficacy and safety of epidural infusions of levobupivacaine with and without
      clonidine for postoperative pain relief in patients undergoing total hip
      replacement.
AB  - We assessed the efficacy and tolerability of epidural infusions of
      levobupivacaine, levobupivacaine plus clonidine, and clonidine for postoperative
      analgesia in 86 patients undergoing total hip replacement. For each group, an
      epidural cannula was inserted before surgery and 15 mL of 0.75% plain
      levobupivacaine was administered. Three hours later, an epidural infusion (6
      mL/h) of levobupivacaine 0.125% (L), levobupivacaine 0.125% plus clonidine 8.3
      microg/mL (LC) or clonidine alone (8.3 microg/mL) (C) was initiated. Morphine
      consumption was recorded for the following 24 h as were visual analog pain scores
      and the degree of sensory and motor blockade. The mean (median) morphine
      consumption was lowest in the combination group (LC),14 (7) mg; higher in the
      clonidine group (C), 23 (21) mg; and highest in the levobupivacaine group (L), 37
      (36) mg (P = 0.022). The median times until the first request for analgesia which
      were 2. 9, 5.9, and 12.5 h for Groups L, C, and LC, respectively (P < or = 0.
      01). There were no statistical differences among the groups regarding the maximum
      degree of postoperative motor blockade. On average, the systolic blood pressure
      in the two clonidine groups was slightly lower than in those from the
      levobupivacaine group. We conclude that the epidural administration of a
      combination of levobupivacaine plus clonidine is well tolerated and gives better
      analgesia than either drug used alone. IMPLICATIONS: In patients undergoing total
      hip replacement, the addition of the alpha(2)-adrenergic agonist clonidine to
      epidural infusions of levobupivacaine significantly improved postoperative
      analgesia.

PMID- 10910856
TI  - The current perception thresholds vary between horizontal and 70 degrees tilt-up
      positions.
AB  - We investigated the influence of posture on current perception threshold (CPT).
      The subjects consisted of 20 healthy male volunteers (23-31 yr old). At both the
      horizontal and the 70 degrees tilt-up position (TUP), the CPTs (5, 250, and 2000
      Hz) of the middle finger were determined by using the Neurometer CPT/C
      (Neuropteran, Baltimore, MD). Autonomic nervous activities were evaluated by
      heart rate variability (HRV) analysis and spontaneous baroreflex sensitivity
      analysis at the two postures previously mentioned. The three CPTs at the 70
      degrees TUP were significantly lower than those at the horizontal posture (5 Hz,
      P < 0.05; 250 Hz, P < 0.001; 2000 Hz, P < 0.05). The changes in HRV and
      spontaneous baroreflex sensitivity at the 70 degrees TUP indicated decreasing
      parasympathetic tone. The CPTs of 5 and 250 Hz were significantly correlated with
      mean systolic blood pressure at the 70 degrees TUP. The CPT of 2000 Hz was
      significantly correlated with the 0.15-0.4 Hz component in HRV at both postures.
      The regression analysis of the difference of 5 Hz CPT with that of the mean
      systolic blood pressure showed a significant correlation (P < 0.001). To evaluate
      the clinical course of peripheral nerve disorders, the comparison of CPTs
      measured during the same posture is important. This suggests that CPTs must be
      measured at the horizontal posture. IMPLICATIONS: Current perception thresholds
      at the 70 degrees tilt-up posture were significantly lower than those at the
      horizontal posture. When the compensatory mechanism for preserving blood pressure
      was emphasized, the current perception thresholds would have a relational
      connection to mean systolic blood pressure, similar to the concept of
      hypertension-induced hypoalgesia.

PMID- 10910857
TI  - Preventing postoperative pain by local anesthetic instillation after laparoscopic
      gynecologic surgery: a placebo-controlled comparison of bupivacaine and
      ropivacaine.
AB  - We tested the hypothesis that local anesthetics instilled at the end of
      laparoscopic gynecologic procedures are able to prevent postoperative pain at
      wake-up and during the first 24 h. A total of 180 patients were randomly assigned
      into three groups to receive an intraperitoneal instillation of 20 mL of either
      bupivacaine 0.5% (Group B), ropivacaine 0.75% (Group R) or saline (Group S) at
      the end of surgery. All patients received analgesia with acetaminophen and
      ketoprofen IV infusions. Pain was assessed by using a 0-10 graded numerical scale
      (NS) every 5 min in the postanesthesia care unit and IV morphine was administered
      if NS was >4. Assessment of pain was continued every 4 h on the ward, and
      subcutaneous morphine was injected if needed to keep the NS score < 4.
      Postoperative nausea and vomiting (PONV) was rated on a 4-point scale. The
      morphine consumption at wake-up and over the first 24 h was significantly lower
      (P < 0.05) in Group B (mean, 0.92 mg at wake-up; 3.08 mg over 24 h) and in Group
      R (mean, 0.25 mg at wake-up; 0.69 mg over 24 h), than in Group S (mean, 4.18 mg
      at wake-up; 12.93 mg over 24 h). The morphine-sparing effect of ropivacaine was
      significantly greater than that of bupivacaine. Both local anesthetics were
      effective in the prevention of PONV. We concluded that local anesthetics should
      be instilled in all gynecologic patients at the end of all laparoscopic
      procedures. IMPLICATIONS: Local anesthetic instillation (ropivacaine rather than
      bupivacaine) at the end of laparoscopy prevents postoperative pain and
      dramatically decreases the need for morphine. This technique, compared with
      placebo, is safe, improves patient comfort, shortens the stay in the
      postoperative care unit and decreases nursing care in the ward.

PMID- 10910858
TI  - The superiority of water-diluted 0.25% to neat 1% lidocaine for trigger-point
      injections in myofascial pain syndrome: a prospective, randomized, double-blinded
      trial.
AB  - Trigger-point injection with a mixture of commercially available 1% lidocaine in
      sterile distilled water at a ratio of 1:3 compared with 1% lidocaine alone
      resulted in better efficacy and less injection pain. This simple procedure may be
      suitable for treatments of a wide range of myofascial pain syndromes.

PMID- 10910859
TI  - The addition of dilute epinephrine produces equieffectiveness of bupivacaine
      enantiomers for cutaneous analgesia in the rat.
AB  - We investigated the effectiveness for cutaneous analgesia of bupivacaine (Bup)
      stereoisomers in male rats. As a model of infiltration anesthesia, inhibition of
      a nocifensive reflex by subcutaneous injection of 0.6 mL of different
      concentrations of R-, S-, and racemic-Bup was evaluated quantitatively by the
      fraction of times a pinprick failed to evoke a nocifensive motor response. R-Bup
      was more potent in the extent of block; however, S-Bup had a longer-lasting
      action at smaller doses. This significant difference was apparent when R-Bup and
      S-Bup were administered in equipotent doses of 0.06% and 0.075%, respectively. Co
      injection of epinephrine (Epi) with these equipotent doses enhanced and prolonged
      the blocking effects of both Bup stereoisomers, although at dilutions of
      1:100,000 to 1:1,000,000 Epi itself induced partial, transient analgesia. At
      1:2,000,000 dilution, Epi alone had no analgesic effect; however, when co
      injected with the shorter-acting R-Bup (0. 06%), Epi prolonged its blocking
      effect to equal the duration of block evoked by equipotent S-Bup (0.075%). We
      conclude R-Bup is more potent for cutaneous analgesia and that the longer
      duration of block by S-Bup probably originates from vasoconstrictor activity.
      IMPLICATIONS: Here we show that the more potent optical R-isomer of bupivacaine
      (Bup) can be used at a smaller dose (80%) than the S-isomer of Bup to give equal
      pain relief of a skin prick. Although the analgesia from R-Bup is briefer than
      that from equipotent S-Bup solutions, the durations become equal when a very
      dilute solution of the vasoconstrictor epinephrine is mixed with the R-isomer.
      The resulting vasoconstriction thus reduces vascular drug uptake and peak blood
      levels of systemic drug, reducing potential toxicity.

PMID- 10910860
TI  - The effect of spinal ibuprofen on opioid withdrawal in the rat.
AB  - This study examines the effect of spinal ibuprofen on the behavioral
      manifestations associated with the opioid abstinence syndrome. Rats (n = 8 per
      group) were infused for 5 days with morphine and then pretreated with a spinal
      bolus dose of ibuprofen before systemic naloxone antagonism (300 microg). Groups
      included ibuprofen S(+) 1. 36, 13.6, and 136 nmol, and ibuprofen R(-) 136 nmol. A
      separate group of saline-infused rats was given ibuprofen S(+) 136 nmol before
      naloxone antagonism. Ibuprofen S(+), but not R(-), dose-dependently and
      stereospecifically blocked opioid withdrawal hyperalgesia but did not
      significantly alter other signs of the opioid abstinence syndrome. We conclude
      that hyperalgesia associated with opioid withdrawal can be blocked by spinally
      administered ibuprofen, and suggest that there may be a role for spinal
      prostaglandins in the enhancement of nociception observed in association with the
      opioid abstinence syndrome. IMPLICATIONS: This study shows that spinal ibuprofen
      blocks opioid withdrawal hyperalgesia in the rat in a stereospecific fashion,
      implicating the likely release of spinal prostaglandins during withdrawal and
      their possible role as neuromodulators in the enhancement of nociception that
      accompanies this phenomenon.

PMID- 10910861
TI  - The effects of intrathecal morphine encapsulated in L- and D
      dipalmitoylphosphatidyl choline liposomes on acute nociception in rats.
AB  - Liposomes can serve as a sustained-release carrier system, permitting the spinal
      delivery of large opioid doses restricting the dose for acute systemic uptake. We
      evaluated the antinociceptive effects of morphine encapsulated in liposomes of
      two isomeric phospholipids, L-dipalmitoylphosphatidyl choline (L-DPPC) and D
      dipalmitoylphosphatidyl choline (D-DPPC), in comparison with morphine in saline.
      Sprague-Dawley rats with chronic lumbar intrathecal catheters were tested for
      their acute nociceptive response using a hindpaw thermal escape test. Their
      general behavior, motor function, pinna reflex, and corneal reflex were also
      examined. The duration of antinociception was longer in both liposomal morphine
      groups than in the free morphine group. The peak antinociceptive effects were
      observed within 30 min after intrathecal morphine, L-DPPC or D-DPPC morphine
      injection. The rank order of the area under the effect-time curve for
      antinociception was L-DPPC morphine > D-DPPC morphine > morphine. The 50%
      effective dose was: 2.7 microg (morphine), 4.6 microg (L-DPPC morphine), and 6.4
      microg (D-DPPC morphine). D-DPPC morphine had less side effects for a given
      antinociceptive AUC than morphine. In conclusion, L-DPPC and D-DPPC liposome
      encapsulation of morphine prolonged the antinociceptive effect on acute thermal
      stimulation and could decrease side effects, compared with morphine alone.
      IMPLICATIONS: Two isomers of liposome (L-dipalmitoylphosphatidyl choline and D
      dipalmitoylphosphatidyl choline) encapsulation of morphine prolonged the
      analgesic effect on acute thermal-induced pain when administered intrathecally
      and could decrease side effects, compared with morphine alone.

PMID- 10910862
TI  - Intrathecal baclofen pump implantation complicated by epidural lipomatosis.
AB  - Intrathecal baclofen is a useful therapy in patients with spasticity. We describe
      a patient who underwent an intrathecal pump implant, complicated by epidural
      lipomatosis that ultimately required a single level laminectomy and fat debulking
      before successful implantation.

PMID- 10910863
TI  - Naloxone-resistant respiratory depression and neurological eye symptoms after
      intrathecal morphine.
AB  - We describe a case of neurological symptoms after the intrathecal use of an
      opioid. These symptoms were not reversible by the use of an opioid-antagonist.

PMID- 10910864
TI  - Compound A concentrations during low-flow sevoflurane anesthesia correlate
      directly with the concentration of monovalent bases in carbon dioxide absorbents.
AB  - Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Potassium
      hydroxide (KOH) and sodium hydroxide (NaOH) are primary determinants of this
      degradation reaction. To address this, new carbon dioxide absorbents, such as
      Amsorb((R)) (A; Armstrong Medical, Coleraine, Northern Ireland), which contains
      neither KOH nor NaOH, Dragersorb 800 Plus((R)) (D; Drager, Luebeck, Germany), and
      Medisorb((R)) (M; Datex-Ohmeda, Bromma, Sweden), which contain some NaOH (1% to
      2%) and only trace amounts of KOH (0.003%), were recently developed. We compared
      Compound A concentrations using these three CO(2) absorbents during low-flow (1
      L/min) sevoflurane anesthesia in surgical patients, with those using a
      conventional CO(2) absorbent, Dragersorb 800 (C). The mean Compound A
      concentrations +/- SD using C, A, D, and M were 18.7 +/- 2.5, 1.8 +/- 0.7, 13.3
      +/- 3.5, and 11.2 +/- 2.6 ppm, respectively, with significant differences (P <
      0.001; A versus C, A versus D, A versus M, C versus D, C versus M). Amsorb
      prevented the degradation of sevoflurane to Compound A, whereas Dragersorb 800
      Plus and Medisorb decreased the degradation to Compound A. IMPLICATIONS:
      Sevoflurane degradation to Compound A is decreased by lowering the concentration
      of monovalent bases in the carbon dioxide absorbent (Dragersorb 800 Plus)
      [Drager, Luebeck, Germany] and Medisorb) [Datex-Ohmeda, Bromma, Sweden]) and is
      virtually eliminated in the absence of these bases (Amsorb) [Armstrong Medical,
      Coleraine, Northern Ireland]).

PMID- 10910865
TI  - Sevoflurane stimulates inositol 1,4,5-trisphosphate in skeletal muscle.
AB  - Inositol 1,4,5-triphosphate (IP(3)) plays an important role in excitation
      contraction coupling and malignant hyperthermia in skeletal muscle. We
      investigated whether sevoflurane affects IP(3) formation in L(6) skeletal muscle
      cells and studied the mechanisms that modulate IP(3). Sevoflurane stimulated
      IP(3) production from a basal level of 78.4 +/- 6.1 to 730.0 +/- 53.1 pmol. mg.
      protein(-1) in 2 mM of sevoflurane in a dose-dependent manner. A dose of 10
      microM of U73122 (a phospholipase C antagonist) significantly decreased 0.8 mM of
      sevoflurane-stimulated IP(3) production from 387. 8 +/- 24.7 to 247.8 +/- 19.8
      pmol. mg. protein(-1). A dose of 100 microM of (p-amylcinnamoyl) anthranilic acid
      (a PLA(2) antagonist) also significantly decreased sevoflurane-stimulated IP(3)
      production to 282.0 +/- 24.0 pmol. mg. protein(-1). Exposure to 1 microM of
      genistein and tyrphostin A23 (tyrosine kinase inhibitors) significantly decreased
      sevoflurane-stimulated IP(3) production to 241.0 +/- 35.3 and 267.4 +/- 32.9
      pmol. mg. protein(-1). Sevoflurane-stimulated IP(3) production was significantly
      decreased by 10 microM of 8-(N,N-diethylamino) octyl-3,4-5-trimathoxybenzoate (an
      intracellular calcium antagonist) and 100 microM and 1 mM of guanosine 5'-O-(2
      thiodiphosphate) (GDPbetaS), a guanosine 5'triphosphate-binding protein
      inhibitor. Elevation of IP(3) production was significantly higher in halothane
      than in sevoflurane and isoflurane at the same concentration of 0.8 mM. We
      conclude that sevoflurane-stimulated IP(3) production involves phospholipase C,
      phospholipase A(2), tyrosine kinase, and guanosine 5'triphosphate-binding protein
      and the stimulation is associated with concentration of intracellular ionized
      calcium. IMPLICATIONS: Inhaled anesthetics increase intracellular ionized calcium
      in the skeletal muscle cell and the ionized calcium increase is partly released
      from the intracellular store by inositol 1,4,5-triphosphate (IP(3)) formation.
      IP(3) plays an important role in excitation-contraction coupling and malignant
      hyperthermia. We studied whether sevoflurane affects IP(3) formation and the
      mechanisms that modulate IP(3).

PMID- 10910866
TI  - Absorption of carbon dioxide by dry soda lime decreases carbon monoxide formation
      from isoflurane degradation.
AB  - This study was performed to determine whether the absorption of carbon dioxide
      (CO(2)) influences the formation of carbon monoxide (CO) from degradation of
      isoflurane in dry soda lime. Isoflurane (0. 5%), CO(2) (5%), a combination of the
      two in oxygen, and pure oxygen were separately passed through samples of 600 g of
      completely dried soda lime (duration of exposure, 60 min; flow rate, 5 L/min).
      Downstream of the soda lime, we measured concentrations of CO, isoflurane, and
      CO(2) as well as the gas temperature. CO(2) increased the peaks of CO
      concentration (842 +/- 81 vs 738 +/- 28 ppm) and shortened the rise time of CO to
      maximum values (12 +/- 2 vs 19 +/- 4 min). However, CO(2) inhibited total CO
      formation (99 +/- 10 vs 145 +/- 6 mL). At the same time, CO(2) absorption by the
      soda lime decreased in the presence of CO formation (from 21.4 +/- 0. 8 to 19.4
      +/- 0.9 g). The temperature of the gases increased during the passage of both
      isoflurane and CO(2) (to 32.6 +/- 2.0 degrees C and 39.4 +/- 4.0 degrees C,
      respectively), but the largest increase (to 41.5 +/- 2.1 degrees C) was recorded
      when isoflurane and CO(2) simultaneously passed through the dry soda lime. We
      assume that the simultaneous reduction in CO formation and CO(2) absorption is
      caused by the competition for the alkali hydroxides present in most of soda lime
      brands. IMPLICATIONS: We determined, in vitro, that carbon monoxide (CO)
      formation from isoflurane by dry soda lime is reduced by carbon dioxide (CO(2)).
      We believe that the potential for injury from CO is less in the clinical milieu
      than suggested by data from experiments without CO(2) because of an
      interdependence between CO formation and CO(2) absorption.

PMID- 10910867
TI  - Between-center variability of results of the in vitro contracture test for
      malignant hyperthermia susceptibility.
AB  - The in vitro contracture test (IVCT) remains the standard test for the diagnosis
      of malignant hyperthermia (MH) susceptibility. The aim of this study was to
      investigate whether results of the IVCT varied between two diagnostic centers.
      The study took place at the national MH centers in Denmark and Sweden. Forty
      three patients investigated for MH gave informed consent to have four extra
      muscle specimens excised. These were sent to the other center and immediately
      used for a parallel IVCT, according to the protocol of the European MH Group.
      Results of the IVCTs performed in the two centers on muscle samples from the same
      patients were compared. Each patient was assigned a diagnosis according to the
      result obtained in the "mother-center." Identical diagnostic results were
      obtained for 56% of the patients. The differing diagnostic outcomes were almost
      exclusively seen in cases with contractures of <5 mN (0.5 g) and abnormal results
      in only one or two muscle strips. We suggest different criteria for the
      interpretation of results for clinical and scientific purposes. The clinical
      criteria should remain unchanged. The scientific designation of susceptibility
      should be used in cases with contractures of > or =5 mN and abnormal results in
      at least 75% of the tested muscle strips. IMPLICATIONS: The diagnostic outcomes
      of tests for malignant hyperthermia susceptibility were compared between two
      laboratories by using muscle tissue from the same patients. Identical outcomes
      were found for 56% of the patients. Almost all diverging outcomes were seen in
      cases with a few small contractures near the cutoff limit. Different diagnostic
      criteria for clinical and scientific purposes are suggested.

PMID- 10910868
TI  - Propofol without muscle relaxants for conventional or fiberoptic nasotracheal
      intubation: a dose-finding study.
AB  - Endotracheal intubation has been performed during the administration of propofol
      anesthesia without neuromuscular blockade. In this study, we determined the
      propofol dose required for conventional nasotracheal or for fiberoptic
      nasotracheal intubation of all patients. Thirty-two patients undergoing
      maxillofacial surgery were randomly assigned to the conventional (n = 16) or to
      the fiberoptic (n = 16) intubation group. In both groups, anesthesia was induced
      by using IV fentanyl and IV titrated propofol according to clinical need
      (spontaneous respiration rate, verbal response). An endotracheal tube was placed
      nasally in the pharynx and the vocal cords visualized by using a fiberscope
      inserted via the tube. In the conventional group, the larynx was visualized
      additionally with a laryngoscope blade (Miller). In both groups propofol was
      titrated until the vocal cords opened. Patients were tracheally intubated, and
      the propofol dose was recorded. In all patients, the trachea could be intubated
      without the use of muscle relaxants. Considerable interindividual differences of
      dose requirements were observed. The amount of propofol required in the
      conventional group was significantly (P < 0.0001) larger (median +/- SD: 2.74 +/-
      1.59 mg/kg; range 1.95-7.07 mg/kg) than in the fiberoptic group (1.37 +/- 0.59
      mg/kg; 0.72-2.86 mg/kg). Hemodynamics remained stable in all patients.
      Postintubational hoarseness occurred in three patients of each group. Fiberoptic
      nasal intubation without a muscle relaxant can be facilitated with significantly
      smaller and more predictable dosages of propofol than conventional nasal
      endotracheal intubation. The possibility of titrating the propofol dose under
      assisted ventilation until the vocal cords open during fiberoptic nasotracheal
      intubation and the better predictability of the required dose favors the
      fiberoptic approach. IMPLICATIONS: In this study, contrary to all preceding
      studies using predefined doses of propofol and opioids, we determined the minimal
      required propofol dose in combination with fentanyl for conventional or
      fiberoptic nasotracheal intubation without muscle relaxants.

PMID- 10910870
TI  - The effects of glycopyrrolate on oral mucous host defenses in healthy volunteers.
AB  - We studied the effects of glycopyrrolate on oral mucous host defenses. Single IV
      doses of glycopyrrolate (4 microg/kg) or placebo were administered to 12 healthy
      volunteers in a randomized, double-blinded, cross-over study. Salivary flow rates
      and the concentrations/activities of total protein, amylase, and nonimmunologic
      (lysozyme, lactoferrin, myeloperoxidase, total salivary peroxidase, and
      thiocyanate) and immunologic (total immunoglobulin A, immunoglobulin G, and
      immunoglobulin M) mucous host defense factors were determined for paraffin
      stimulated whole saliva before and 1, 3, 6, 12, 24, and 48 h after drug
      administration. Glycopyrrolate serum concentrations were determined before and 2,
      4, 6, 10, 15, and 30 min and 1, 2, 3, 6, 12, and 24 h after IV drug injection.
      Salivary flow rates were decreased significantly for 12 h after glycopyrrolate
      injection, compared with saline injection. The concentrations of immunologic and
      nonimmunologic defense factors were increased in the glycopyrrolate group, and
      differences between the groups were found for all factors (P < 0.05-0.001) except
      lysozyme and total salivary peroxidase. In contrast, because of the reduced flow
      rate, the output of all defense factors into the saliva was decreased after
      glycopyrrolate injection, compared with saline injection. Glycopyrrolate thus
      decreases the output of salivary host defense factors into the oral cavity.
      IMPLICATIONS: Glycopyrrolate induces long-lasting hyposalivation and decreases
      the secretion of salivary immunologic and nonimmunologic defense factors in
      healthy volunteers.

PMID- 10910869
TI  - Inhaled anesthetics have hyperalgesic effects at 0.1 minimum alveolar anesthetic
      concentration.
AB  - We investigated the hyperalgesic (antianalgesic) effect of the inhaled
      anesthetics isoflurane, halothane, nitrous oxide, and diethyl ether, or the
      nonimmobilizer 1, 2-dichlorohexafluorocyclobutane at subanesthetic partial
      pressures (or, for the nonimmobilizer, subanesthetic partial pressures predicted
      from lipid solubility) in rats. Hyperalgesia was assessed as a decrease in the
      time to withdrawal of a rat hind paw exposed to heat. All four anesthetics,
      including nitrous oxide and diethyl ether, produced hyperalgesia at low partial
      pressures, with a maximal effect at 0.1 minimum alveolar anesthetic concentration
      (MAC) required to prevent response to movement in 50% of animals, and analgesia
      (an increased time to withdrawal of the hind paw) at 0. 4 to 0.8 MAC. The
      nonimmobilizer had neither analgesic nor hyperalgesia effects. We propose that
      inhaled anesthetics with a higher MAC-Awake (the MAC-fraction that suppresses
      appropriate responsiveness to command), such as nitrous oxide and diethyl ether,
      can be used as analgesics because patients are conscious at higher anesthetic
      partial pressures, including those which have analgesic effects, whereas
      anesthetics with a lower MAC-Awake do not produce analgesic effects at
      concentrations that permit consciousness. IMPLICATIONS: The inhaled anesthetics
      isoflurane, halothane, nitrous oxide, and diethyl ether produce antianalgesia at
      subanesthetic concentrations, with a maximal effect at approximately one-tenth
      the concentration required for anesthesia. This effect may enhance perception of
      pain when such small concentrations are reached during recovery from anesthesia.

PMID- 10910871
TI  - The comparative dose-response effects of melatonin and midazolam for
      premedication of adult patients: a double-blinded, placebo-controlled study.
AB  - We designed this prospective, randomized, double-blinded, placebo-controlled
      study to compare the perioperative effects of different doses of melatonin and
      midazolam. Doses of 0.05, 0.1, or 0. 2 mg/kg sublingual midazolam or melatonin or
      placebo were given to 84 women, approximately 100 min before a standard
      anesthetic. Sedation, anxiety, and orientation were quantified before, 10, 30,
      60, and 90 min after premedication, and 15, 30, 60, and 90 min after admission to
      the recovery room. Psychomotor performance of the patient was evaluated at these
      times also, by using the digit-symbol substitution test and Trieger dot test.
      Patients who received premedication with either midazolam or melatonin had a
      significant decrease in anxiety levels and increase in levels of sedation
      preoperatively compared with control subjects. Patients in the three midazolam
      groups experienced significant psychomotor impairment in the preoperative period
      compared with melatonin or placebo. After operation, patients who received 0.2
      mg/kg midazolam premedication had increased levels of sedation at 90 min compared
      with 0.05 and 0. 1 mg/kg melatonin groups. In addition, patients in the three
      midazolam groups had impairment of performance on the digit-symbol substitution
      test at all times compared with the 0.05 mg/kg melatonin group. Premedication
      with 0.05 mg/kg melatonin was associated with preoperative anxiolysis and
      sedation without impairment of cognitive and psychomotor skills or affecting the
      quality of recovery. IMPLICATIONS: Premedication with 0.05 mg/kg melatonin was
      associated with preoperative anxiolysis and sedation without impairment of
      cognitive and psychomotor skills or affecting the quality of recovery.

PMID- 10910872
TI  - Isoflurane does not depress the hypoxic response of rabbit carotid body
      chemoreceptors.
AB  - Whether volatile anesthetics have an effect on the peripheral chemoreceptors is
      controversial, possibly because of differences in end-tidal CO(2) concentrations.
      We studied the effect of isoflurane on the hypoxic chemosensitivity of carotid
      body chemoreceptors at three different PaCO(2) levels before and during the
      administration of 1.0% isoflurane (0.5 minimum alveolar anesthetic concentration)
      in six normothermic New Zealand white rabbits anesthetized with thiopental. The
      response of the chemoreceptors was fitted to the equation: Frequency (Hz) = a + b
      x PaCO(2) + c x (1/PaO(2)) + Dx (1/PaO(2))(2). Mean values for the coefficients
      a, b, c and d for the control state were -4.5, 0.13, 771, and 6332, respectively.
      This relationship was not changed by addition of isoflurane at 1.0% end-tidal
      concentration (P = 0.40, analysis of variance). We conclude that isoflurane at
      1.0% end-tidal concentration does not depress the hypoxic response of rabbit
      carotid body chemoreceptors during either hypo-, normo-, or hypercapnia.
      IMPLICATIONS: By measuring single-fiber chemoreceptor activity in anesthetized
      rabbits, we showed that isoflurane at 1.0% end-tidal concentration does not
      depress the hypoxic chemosensitivity of peripheral chemoreceptors during either
      hypo-, normo-, or hypercapnia in this species.

PMID- 10910873
TI  - Analgesia and anesthesia: etymology and literary history of related Greek words.

PMID- 10910874
TI  - Vecuronium-induced neuromuscular blockade in a patient with cerebral palsy and
      hemiplegia.
AB  - We evaluated vecuronium-induced neuromuscular block in both arms of a patient
      with cerebral palsy and hemiplegia. A remarkable resistance to vecuronium was
      observed in the hemiplegia side compared with cerebral palsy side. Complete
      recovery from neuromuscular block should be assessed in the cerebral palsy side
      that shows a delayed recovery.

PMID- 10910875
TI  - Bearded Sikhs and tracheal intubation.

PMID- 10910876
TI  - Additional view of the mitral valve.

PMID- 10910877
TI  - Airway obstruction from uvular edema after traumatic adenoidectomy.

PMID- 10910878
TI  - Drug company-supported symposia: what should be disclosed?

PMID- 10910879
TI  - Difficult airway management with Fogarty catheter balloon inflation.

PMID- 10910880
TI  - Ondansetron and evidence-based medicine.

PMID- 10910881
TI  - Cannabis is not equivalent to cannabinoids.

PMID- 10910882
TI  - Antifibrinolytic therapy reduces blood loss in knee replacement surgery.

PMID- 10910883
TI  - Misdiagnosis of ECG artifacts may lead to drastic and unnecessary interventions.

PMID- 10910884
TI  - Transesophageal echocardiographic diagnosis of acute aortic valve insufficiency
      after mitral valve repair.

PMID- 10910885
TI  - Anesthesia for fetal intervention.

PMID- 10910886
TI  - Two suggestions to facilitate patient positioning in the performance of regional
      anesthesia.

PMID- 10910887
TI  - Use of a fiberscope and closed-circuit television for teaching laryngeal mask
      insertion.

PMID- 10910888
TI  - Prolonged survival and tissue trafficking following adoptive transfer of CD4zeta
      gene-modified autologous CD4(+) and CD8(+) T cells in human immunodeficiency
      virus-infected subjects.
AB  - We have genetically engineered CD4(+) and CD8(+) T cells with human
      immunodeficiency virus (HIV) specificity by inserting a gene, CD4zeta, containing
      the extracellular domain of human CD4 (which binds HIV env) linked to the zeta
      (zeta) chain of the T-cell receptor (which mediates T-cell activation). Twenty
      four HIV-positive subjects received a single infusion of 2 to 3 x 10(10)
      autologous CD4zeta-modified CD4(+) and CD8(+) T cells administered with (n = 11)
      or without (n = 13) interleukin-2 (IL-2). Subjects had CD4 counts greater than
      50/microL and viral loads of at least 1000 copies/mL at entry. T cells were
      costimulated ex vivo through CD3 and CD28 and expanded for approximately 2 weeks.
      CD4zeta was detected in 1% to 3% of blood mononuclear cells at 8 weeks and 0.1%
      at 1 year after infusion, and survival was not enhanced by IL-2. Trafficking of
      gene-modified T cells to bulk rectal tissue and/or isolated lamina propria
      lymphocytes was documented in a subset of 5 of 5 patients at 14 days and 2 of 3
      at 1 year. A greater than 0.5 log mean decrease in rectal tissue-associated HIV
      RNA was observed for at least 14 days, suggesting compartmental antiviral
      activity of CD4zeta T cells. CD4(+) counts increased by 73/microL at 8 weeks in
      the group receiving IL-2. There was no significant mean change in plasma HIV RNA
      or blood proviral DNA in either treatment arm. This sustained, high-level
      persistence of gene-modified T cells demonstrates the feasibility of ex vivo T
      cell gene therapy in HIV-infected adults and suggests the importance of providing
      HIV-specific T-helper function.

PMID- 10910889
TI  - Molecular characterization of a granulocyte macrophage-colony-stimulating factor
      receptor alpha subunit-associated protein, GRAP.
AB  - The granulocyte macrophage-colony-stimulating factor receptor (GM-CSF-R) is a
      heterodimer composed of 2 subunits, alpha and beta, and ligand binding to the
      high-affinity receptor leads to signalling for the multiple actions of GM-CSF on
      target cells. In order to explore the role of the alpha subunit in signalling, we
      used a yeast-2-hybrid system to identify proteins interacting with the
      intracellular domain of the GMR-alpha. A cDNA encoding a predicted protein of 198
      amino acids, designated GRAP (GM-CSF receptor alpha subunit-associated protein),
      was isolated in experiments using the intracellular portion of GMR-alpha as bait.
      The interaction between GRAP and GMR-alpha was confirmed by coimmunoprecipitation
      in mammalian cells. GRAP mRNA is widely expressed in normal human and mouse
      tissues and in neoplastic human cell lines, but it is not restricted to cells or
      tissues that express GM-CSF receptors. Three discrete GRAP mRNA species were
      detected in human tissues and cells, with estimated sizes of 3.3, 3.1, and 1.3
      kb. GRAP is highly conserved throughout evolution, and homologues are found in
      yeast. The GRAP locus in Saccharomyces cerevisiae was disrupted, and mutant yeast
      cells showed an inappropriate stress response under normal culture conditions,
      manifested by early accumulation of glycogen during the logarithmic growth phase.
      GRAP is, therefore, a highly conserved and widely expressed protein that binds to
      the intracellular domain of GMR-alpha, and it appears to play an important role
      in cellular metabolism.

PMID- 10910890
TI  - alpha-thalassemia resulting from a negative chromosomal position effect.
AB  - To date, all of the chromosomal deletions that cause alpha-thalassemia remove the
      structural alpha genes and/or their regulatory element (HS -40). A unique
      deletion occurs in a single family that juxtaposes a region that normally lies
      approximately 18-kilobase downstream of the human alpha cluster, next to a
      structurally normal alpha-globin gene, and silences its expression. During
      development, the CpG island associated with the alpha-globin promoter in the
      rearranged chromosome becomes densely methylated and insensitive to
      endonucleases, demonstrating that the normal chromatin structure around the alpha
      globin gene is perturbed by this mutation and that the gene is inactivated by a
      negative chromosomal position effect. These findings highlight the importance of
      the chromosomal environment in regulating globin gene expression.

PMID- 10910891
TI  - The role of immunoglobulin translocations in the pathogenesis of B-cell
      malignancies.

PMID- 10910892
TI  - Erythropoietin, iron, and erythropoiesis.
AB  - Recent knowledge gained regarding the relationship between erythropoietin, iron,
      and erythropoiesis in patients with blood loss anemia, with or without
      recombinant human erythropoietin therapy, has implications for patient
      management. Under conditions of significant blood loss, erythropoietin therapy,
      or both, iron-restricted erythropoiesis is evident, even in the presence of
      storage iron and iron oral supplementation. Intravenous iron therapy in renal
      dialysis patients undergoing erythropoietin therapy can produce hematologic
      responses with serum ferritin levels up to 400 microg/L, indicating that
      traditional biochemical markers of storage iron in patients with anemia caused by
      chronic disease are unhelpful in the assessment of iron status. Newer
      measurements of erythrocyte and reticulocyte indices using automated counters
      show promise in the evaluation of iron-restricted erythropoiesis. Assays for
      serum erythropoietin and the transferrin receptor are valuable tools for clinical
      research, but their roles in routine clinical practice remain undefined. The
      availability of safer intravenous iron preparations allows for carefully
      controlled studies of their value in patients undergoing erythropoietin therapy
      or experiencing blood loss, or both.

PMID- 10910893
TI  - Induction of monocyte- and T-cell-attracting chemokines in the lung during the
      generation of idiopathic pneumonia syndrome following allogeneic murine bone
      marrow transplantation.
AB  - Idiopathic pneumonia syndrome (IPS) is a significant complication following bone
      marrow transplantation (BMT). We have developed a murine model in which severe
      IPS is induced by pre-BMT conditioning and allogeneic T cells and is
      characterized by the recruitment of host monocytes and donor T cells into the
      lung by day 7 post-BMT. Chemokines regulate cellular recruitment and the
      migration of cells into inflammatory lesions. In this study, we examined the
      profiles of chemokines produced locally in the lung (parenchyma and
      bronchoalveolar lavage fluid) and systemically (serum) during the generation of
      IPS in the peri-BMT period. Protein and messenger RNA (mRNA) levels of CC
      chemokines (monocyte/lymphocyte attractants), especially monocyte chemoattractant
      protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated
      upon activation normal T-cell expressed and secreted), and C10, were
      preferentially induced in the lung by day 7 postallogeneic BMT. In addition,
      there was an increase in mRNA for IP-10 (a monocyte and Th1-cell
      chemoattractant). The CXC chemokines MIP-2 and KC, known neutrophil attractants,
      were moderately elevated. For the most part, these increases in chemokines were
      dependent on the coinfusion of allogeneic T cells with the BM inoculum.
      Ribonuclease protection assay and in situ hybridization analyses post-BMT showed
      that the lung was a major producer of MCP-1, a potent inducer of monocyte
      chemotaxis. Increases in MCP-1 levels in the lung preceded host APC influx
      whereas MIP-1alpha levels accompanied donor T-cell infiltration. In summary, we
      have shown that monocyte- and T-cell-attracting chemokines are associated with
      monocyte and T-cell recruitment during IPS.

PMID- 10910894
TI  - LEC induces chemotaxis and adhesion by interacting with CCR1 and CCR8.
AB  - Liver-expressed chemokine (LEC) is an unusually large CC chemokine, which is also
      known as LMC, HCC-4, NCC-4, and CCL16. Previously, LEC was shown to induce
      leukocyte migration but the responsible signaling receptors were not
      characterized. We report chemotaxis and competitive binding studies that show LEC
      binds to and activates CCR1 and CCR8 transfected HEK-293 cells. LEC induced
      maximal migration of CCR1 and CCR8 transfected cells at 89.3 nmol/L and cell
      adhesion at 5.6 nmol/L. The molar concentration of LEC required to induce maximum
      cell migration is 20- to 200-fold greater than that required for RANTES or I309,
      respectively. All 3 chemokines induced maximal static adhesion at 5 to 7 nmol/L.
      A neutralizing polyclonal antibody to LEC was developed to demonstrate that the
      unusually high concentration of LEC required to induce chemotaxis was a property
      of LEC and not as a result of an irrelevant protein contamination. This study
      suggests that LEC may be a more effective inducer of cell adhesion than cell
      migration.

PMID- 10910895
TI  - Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis
      of 2 prospective trials to assess the value of parenteral treatment with
      lepirudin and its therapeutic aPTT range.
AB  - This meta-analysis focuses on 2 prospective studies in patients with heparin
      induced thrombocytopenia (HIT) and thromboembolic complication (TEC) who were
      treated with lepirudin (n = 113). Data were compared with those of a historical
      control group (n = 91). The primary endpoint (combined incidence of death, new
      TEC, and limb amputation) occurred in 25 lepirudin-treated patients (22.1%; 95%
      CI, 14.5%-29.8%): 11 died (9.7%; 95% CI, 4.9%-16.8%), 7 underwent limb amputation
      (6.2%; 95% CI, 2.5%-12.3%), and 12 experienced new TEC (10.6%; 95% CI, 5.8%
      18.3%). The risk was highest in the period between diagnosis of HIT and the start
      of lepirudin therapy (combined event rate per patient day 6.1%). It markedly
      decreased to 1.3% during lepirudin treatment and to 0.7% in the posttreatment
      period. From the start of lepirudin therapy to the end of follow-up, lepirudin
      treated patients had consistently lower incidences of the combined endpoint than
      the historical control group (P =.004, log-rank test), primarily because of a
      reduced risk for new TEC (P =. 005). Thrombin-antithrombin levels in the
      pretreatment period (median, 43.9 microg/L) decreased after the initiation of
      lepirudin (at 24 hours +/- 6 hours; median, 9.18 microg/L.) During treatment with
      lepirudin, aPTT ratios of 1.5 to 2.5 produced optimal clinical efficacy with a
      moderate risk for bleeding, aPTT ratios lower than 1. 5 were subtherapeutic, and
      aPTT levels greater than 2.5 were associated with high bleeding risk. Bleeding
      events requiring transfusion were significantly more frequent in patients taking
      lepirudin than in historical control patients (P =.02). In conclusion, this meta
      analysis provides further evidence that lepirudin is an effective and acceptably
      safe treatment for patients with HIT.

PMID- 10910896
TI  - patients with the description of a new scoring system and its validation on 253
      other patients.
AB  - Using Cox models, we established a new prognostic system based on simple clinical
      parameters in a training series of 232 patients whose diagnoses were made before
      1989. Adverse prognostic factors for survival (P <.01) were age 65 years or
      older, male gender, albumin level lower than 40 g/L, hemoglobin level lower than
      12 g/dL, platelet count less than 150 x 10(9)/L, white blood cell count less than
      4 x 10(9)/L, high number of cytopenias, and hepatomegaly. Taking age (age 65
      years or older, 1 point; younger than 65 years, 0 points), albumin (less than 40
      g/L, 1 point; 40 g/L or more, 0 points), and total number of cytopenias (no
      cytopenia, 0 points; 1 cytopenia, 1 point; 2 or 3 cytopenias, 2 points) into
      account, we separated the 232 patients into 3 groups with low (score 0 or 1),
      intermediate (score 2), or high (score 3 or 4) risk, associated with 5-year
      survival rates at 87%, 62%, and 25%, respectively (P <.0001). Only the presence
      of 2 or 3 cytopenias was an independent prognostic factor among patients younger
      than 65 years (P <.0001). Albumin level lower than 40 g/L and the presence of 1
      or more cytopenia defined a prognostic system for patients 65 years and older.
      Patients at low risk, intermediate risk, and high risk had 5-year survival rates
      at 92%, 63%, and 27%, respectively (P <.0001). The 3 prognostic systems separated
      the 167 patients of a test series in groups with significantly different survival
      rates. The overall scoring system retained a significant prognostic value in 86
      additional patients treated between 1990 and 1996. We conclude that the
      combination of age, albumin level, and blood cell counts might help to select
      patients with Waldenstrom macroglobulinemia for treatment and to evaluate
      therapeutic results.

PMID- 10910897
TI  - Constitutive elevation of serum alpha-fetoprotein in Fanconi anemia.
AB  - The diagnosis of Fanconi anemia (FA) is based on the association of congenital
      malformations, bone marrow failure syndrome, and hypersensitivity to chromosomal
      breaks induced by cross-linking agents. In the absence of typical features, the
      diagnosis is not easy to establish because there is no simple and cost-effective
      test; thus, investigators must rely on specialized analyses of chromosomal
      breaks. Because we observed elevated serum alpha-fetoprotein (sAFP) levels in FA
      patients, we investigated this parameter as a possible diagnostic tool. Serum AFP
      levels from 61 FA patients and 27 controls with acquired aplastic anemia or other
      inherited bone marrow failure syndromes were analyzed using a fluoroimmunoassay
      based on the TRACE technology. Serum AFP levels were significantly more elevated
      (P <.0001) in FA than in non-FA aplastic patients. In the detection of FA
      patients among patients with bone marrow failure syndromes, this assay had a
      sensitivity of 93% and a specificity of 100%. This elevation was not explained by
      liver abnormalities. Levels of sAFP were unchanged during at least 4 years of
      follow-up, and allogeneic bone marrow transplantation did not modify sAFP levels.
      Three of 4 FA patients with mosaicism as well as 5 of 6 FA patients with
      myelodysplastic syndrome were detected by this test. Heterozygous parents of FA
      patients had normal sAFP levels. Measurement of sAFP levels with this automated,
      cost-effective, and reproducible fluoroimmunoassay could be proposed for the
      preliminary diagnosis of FA whenever this disorder is suspected.

PMID- 10910898
TI  - Successful in vivo purging of CD34-containing peripheral blood harvests in mantle
      cell and indolent lymphoma: evidence for a role of both chemotherapy and
      rituximab infusion.
AB  - Elimination of tumor cells ("purging") from hematopoietic stem cell products is a
      major goal of bone marrow-supported high-dose cancer chemotherapy. We developed
      an in vivo purging method capable of providing tumor-free stem cell products from
      most patients with mantle cell or follicular lymphoma and bone marrow
      involvement. In a prospective study, 15 patients with CD20(+) mantle cell or
      follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)
      detectable molecular rearrangement received 2 cycles of intensive chemotherapy,
      each of which was followed by infusion of a growth factor and 2 doses of the anti
      CD20 monoclonal antibody rituximab. The role of rituximab was established by
      comparison with 10 control patients prospectively treated with an identical
      chemotherapy regimen but no rituximab. The CD34(+) cells harvested from the
      patients who received both chemotherapy and rituximab were PCR-negative in 93% of
      cases (versus 40% of controls; P =.007). Aside from providing PCR-negative
      harvests, the chemoimmunotherapy treatment produced complete clinical and
      molecular remission in all 14 evaluable patients, including all 6 with mantle
      cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic
      progenitor cells can be successfully accomplished in most patients with CD20(+)
      lymphoma, including mantle cell lymphoma. The results depended on the activity of
      both chemotherapy and rituximab infusion and provide the proof of principle that
      in vivo purging is feasible and possibly superior to currently available ex vivo
      techniques. The high short-term complete-response rate observed suggests the
      presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy
      combination used.

PMID- 10910899
TI  - The immunophenotype of 177 adults with acute myeloid leukemia: proposal of a
      prognostic score.
AB  - In acute myeloid leukemia (AML) patients, a variety of clinical and biologic
      parameters, including phenotype, have been examined for potential value in
      predicting treatment response and survival. The European Group for the
      Immunological Classification of Leukaemias (EGIL) has proposed that AML be
      defined immunologically by the expression of 2 or more of the following myeloid
      markers: myeloperoxidase, CD13, CD33, CDw65, and CD117. With regard to this
      classification, the prognostic significance of 21 antigens taken separately and
      with immunophenotypic subgroups were evaluated and compared with other clinical
      and biological variables in 177 adult AML patients. None of the antigens tested
      were associated with treatment outcome. In contrast, patients with blasts
      disclosing a full expression of panmyeloid phenotype (defined by the expression
      of all 5 myeloid markers) had a higher complete remission rate (P <. 0001) and
      differed significantly in disease-free survival (P =.02) and overall survival (P
      =.008) than patients whose cells expressed fewer than 5 of these markers. In
      multivariate analysis, only age, panmyeloid phenotype, performance status, and
      permeability glycoprotein activity influence treatment outcome. Cytogenetics was
      significant in univariate analysis but not in multivariate analysis, most likely
      because of the redundancy with panmyeloid phenotype and a higher sensitivity of
      immunophenotyping. Patients whose cells exhibit the panmyeloid phenotype appear
      to define a relatively homogeneous biological subset of AML. The 4 independent
      prognostic factors were used to create a prognostic score, defined by the number
      of factors present. This score permitted a stratification of patients with AML,
      thereby allowing for the consideration of innovative therapies to improve outcome
      in the poorer outcome groups.

PMID- 10910900
TI  - In vivo generation of human dendritic cell subsets by Flt3 ligand.
AB  - Dendritic cells (DCs) represent a family of ontogenically distinct leukocytes
      involved in immune response regulation. The ability of DCs to stimulate T-cell
      immunity has led to their use as vectors for immunotherapy vaccines. However, it
      is unclear whether and to what degree in vitro-generated DCs are representative
      of DCs that develop in vivo. Treatment of mice with human Flt3 ligand (FL)
      dramatically increases the number of DCs. We report here that administration of
      FL to healthy human volunteers increased the number of circulating CD11c(+ )IL
      3Ralpha(low) DC (mean 44-fold) and CD11c(-) IL-3Ralpha(high) DC precursors (mean
      12-fold). Moreover, the CD11c(+ )DCs were efficient stimulators of T cells in
      vitro. Thus, FL can expand the number of circulating, functionally competent
      human DCs in vivo.

PMID- 10910901
TI  - Highly efficient gene transfer in naive human T cells with a murine leukemia
      virus-based vector.
AB  - Retroviral vectors based on the Moloney murine leukemia virus (MuLV) have become
      the primary tool for gene delivery into hematopoietic cells, but clinical trials
      have been hampered by low transduction efficiencies. Recently, we and others have
      shown that gene transfer of MuLV-based vectors into T cells can be significantly
      augmented using a fibronectin-facilitated protocol. Nevertheless, the relative
      abilities of naive (CD45RA(+)) and memory (CD45RO(+)) lymphocyte subsets to be
      transduced has not been assessed. Although naive T cells demonstrate a restricted
      cytokine profile following antigen stimulation and a decreased susceptibility to
      infection with human immunodeficiency virus, it was not clear whether they could
      be efficiently infected with a MuLV vector. This study describes conditions that
      permitted gene transfer of an enhanced green fluorescent protein-expressing
      retroviral vector in more than 50% of naive umbilical cord (UC) blood and
      peripheral blood (PB) T cells following CD3/CD28 ligation. Moreover, treatment of
      naive T cells with interleukin-7 resulted in the maintenance of a CD45RA
      phenotype and gene transfer levels approached 20%. Finally, it was determined
      that parameters for optimal transduction of CD45RA(+) T cells isolated from PB
      and UC blood differed: transduction of the UC cells was significantly increased
      by the presence of autologous mononuclear cells (24.5% versus 56.5%). Because
      naive T cells harbor a receptor repertoire that allows them to respond to novel
      antigens, the development of protocols targeting their transduction is crucial
      for gene therapy applications. This approach will also allow the functions of
      exogenous genes to be evaluated in primary nontransformed naive T cells.

PMID- 10910902
TI  - Inactivation of a GFP retrovirus occurs at multiple levels in long-term
      repopulating stem cells and their differentiated progeny.
AB  - Hematopoietic stem cell gene therapy holds promise for the treatment of many
      hematologic disorders. One major variable that has limited the overall success of
      gene therapy to date is the lack of sustained gene expression from viral vectors
      in transduced stem cell populations. To understand the basis for reduced gene
      expression at a single-cell level, we have used a murine retroviral vector, MFG,
      that expresses the green fluorescent protein (GFP) to transduce purified
      populations of long-term self-renewing hematopoietic stem cells (LT-HSC) isolated
      using the fluorescence-activated cell sorter. Limiting dilution reconstitution of
      lethally irradiated recipient mice with 100% transduced, GFP(+) LT-HSC showed
      that silencing of gene expression occurred rapidly in most integration events at
      the LT-HSC level, irrespective of the initial levels of GFP expression. When
      inactivation occurred at the LT-HSC level, there was no GFP expression in any
      hematopoietic lineage clonally derived from silenced LT-HSC. Inactivation
      downstream of LT-HSC that stably expressed GFP( )in long-term reconstituted
      animals was restricted primarily to lymphoid cells. These observations suggest at
      least 2 distinct mechanisms of silencing retrovirally expressed genes in
      hematopoietic cells.

PMID- 10910903
TI  - Enforced P-glycoprotein pump function in murine bone marrow cells results in
      expansion of side population stem cells in vitro and repopulating cells in vivo.
AB  - The human multidrug resistance-1 (MDR1) gene product, P-glycoprotein (P-gp), is
      well known for its ability to confer drug resistance; however, recent evidence
      suggests that P-gp expression can have more general effects on cellular
      development. In support of this idea, it was previously shown that retroviral
      mediated MDR1 expression in murine bone marrow cells resulted in the expansion of
      stem cells in culture and in the development of a myeloproliferative syndrome in
      transplanted mice. It is now reported that MDR1-mediated stem cell expansion is
      associated with an increase in side population (SP) stem cells, defined by
      Hoechst dye staining. Transduction of murine bone marrow cells with an MDR1
      retroviral vector resulted in an almost 2 log increase in SP cell numbers over 12
      days in culture, whereas there was a rapid loss of SP cells from control
      cultures. Stem cell amplification was not limited to ex vivo expansion cultures
      but was also evident when MDR1-transduced cells were directly transplanted into
      irradiated mice. In these cases, stem cell expansion was associated with
      relatively high vector copy numbers in stem cell clones. As previously reported,
      some cases were associated with a characteristic myeloproliferative syndrome. A
      functionally inactive MDR1 mutant cDNA was used to show that P-gp pump function
      was required both for amplification of phenotypically defined SP cells and
      functionally defined repopulating cells. These studies further support the
      concept that ABC transporter function can have important effects on hematopoietic
      stem cell development.

PMID- 10910904
TI  - GATA factor transgenes under GATA-1 locus control rescue germline GATA-1 mutant
      deficiencies.
AB  - GATA-1 germline mutation in mice results in embryonic lethality due to defective
      erythroid cell maturation, and thus other hematopoietic GATA factors do not
      compensate for the loss of GATA-1. To determine whether the obligate presence of
      GATA-1 in erythroid cells is due to its distinct biochemical properties or
      spatiotemporal patterning, we attempted to rescue GATA-1 mutant mice with
      hematopoietic GATA factor complementary DNAs (cDNAs) placed under the
      transcriptional control of the GATA-1 gene. We found that transgenic expression
      of a GATA-1 cDNA fully abrogated the GATA-1-deficient phenotype. Surprisingly,
      GATA-2 and GATA-3 factors expressed from the same regulatory cassette also
      rescued the embryonic lethal phenotype of the GATA-1 mutation. However, adult
      mice rescued with the latter transgenes developed anemia, while GATA-1 transgenic
      mice did not. These results demonstrate that the transcriptional control
      dictating proper GATA-1 accumulation is the most critical determinant of GATA-1
      activity during erythropoiesis. The results also show that there are biochemical
      distinctions among the hematopoietic GATA proteins and that during adult
      hematopoiesis the hematopoietic GATA factors are not functionally equivalent.

PMID- 10910905
TI  - Expression of connexin 43 (Cx43) is critical for normal hematopoiesis.
AB  - Gap junctions are intercellular channels, formed by individual structural units
      known as connexins (Cx), that allow the intercellular exchange of various
      messenger molecules. The finding that numbers of Cx43-type gap junctions in bone
      marrow are elevated during establishment and regeneration of the hematopoietic
      system has led to the hypothesis that expression of Cx43 is critical during the
      initiation of blood cell formation. To test this hypothesis, lymphoid and myeloid
      development were examined in mice with a targeted disruption of the gene encoding
      Cx43. Because Cx43-/- mice die perinatally, initial analyses were performed on
      Cx43-/-, Cx43+/-, and Cx43+/+ embryos and newborns. The data indicate that lack
      of Cx43 expression during embryogenesis compromises the terminal stages of
      primary T and B lymphopoiesis. Cx43-/- embryos and neonates had a reduced
      frequency of CD4(+) and T-cell receptor-expressing thymocytes and surface IgM(+)
      cells compared to their Cx43+/+ littermates. Surprisingly, Cx43+/-
      embryos/neonates also showed defects in B- and T-cell development similar to
      those observed in Cx43-/- littermates, but their hematopoietic system was normal
      at 4 weeks of age. However, the regeneration of lymphoid and myeloid cells was
      severely impaired in the Cx43+/- mice after cytoablative treatment. Taken
      together, these data indicate that loss of a single Cx43 allele can affect blood
      cell formation. Finally, the results of reciprocal bone marrow transplants
      between Cx43+/+ and Cx43+/- mice and examination of hematopoietic progenitors and
      stromal cells in vitro indicates that the primary effects of Cx43 are mediated
      through its expression in the hematopoietic microenvironment.

PMID- 10910906
TI  - Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective
      tyrosine kinase inhibitor.
AB  - STI 571 (formerly known as CGP 57148B) is a known inhibitor of the c-abl, bcr
      abl, and platelet-derived growth-factor receptor (PDGFR) tyrosine kinases. This
      compound is being evaluated in clinical trials for the treatment of chronic
      myelogenous leukemia. We sought to extend the activity profile of STI 571 by
      testing its ability to inhibit the tyrosine kinase activity of c-kit, a receptor
      structurally similar to PDGFR. We treated a c-kit expressing a human myeloid
      leukemia cell line, M-07e, with STI 571 before stimulation with Steel factor
      (SLF). STI 571 inhibited c-kit autophosphorylation, activation of mitogen
      activated protein (MAP) kinase, and activation of Akt without altering total
      protein levels of c-kit, MAP kinase, or Akt. The concentration that produced 50%
      inhibition for these effects was approximately 100 nmol/L. STI 571 also
      significantly decreased SLF-dependent growth of M-07e cells in a dose-dependent
      manner and blocked the antiapoptotic activity of SLF. In contrast, the compound
      had no effect on MAP kinase activation or cellular proliferation in response to
      granulocyte-macrophage colony-stimulating factor. We also tested the activity of
      STI 571 in a human mast cell leukemia cell line (HMC-1), which has an activated
      mutant form of c-kit. STI 571 had a more potent inhibitory effect on the kinase
      activity of this mutant receptor than it did on ligand-dependent activation of
      the wild-type receptor. These findings show that STI 571 selectively inhibits c
      kit tyrosine kinase activity and downstream activation of target proteins
      involved in cellular proliferation and survival. This compound may be useful in
      treating cancers associated with increased c-kit kinase activity.

PMID- 10910907
TI  - JNK and p38 are activated by erythropoietin (EPO) but are not induced in
      apoptosis following EPO withdrawal in EPO-dependent HCD57 cells.
AB  - Jun N-terminal kinase (JNK) and p38, members of the mitogen-activated protein
      kinase family of serine/threonine kinases, are activated as a result of cellular
      stress but may also play a role in growth factor-induced proliferation and/or
      survival or differentiation of many cells. A recent report has implicated JNK and
      p38 in the induction of apoptosis in the erythropoietin (EPO)-dependent erythroid
      cell line HCD57 following EPO withdrawal, whereas our previously reported data
      did not support a role for JNK in growth factor withdrawal-induced apoptosis in
      HCD57 cells. Therefore, further testing was done to see if JNK was activated in
      EPO withdrawal-induced apoptosis; the study was extended to p38 and characterized
      the effect of EPO on JNK and p38 activities. Treatment of HCD57 cells with EPO
      resulted in a gradual and sustained activation of both JNK and p38 activity;
      these activities decreased on EPO withdrawal. Transient activation of p42/p44
      extracellular signal-related kinases (ERK) was also detected. Inhibition of ERK
      activity inhibited proliferation in EPO-treated cells but neither induced
      apoptosis nor activated JNK. Inhibition of p38 activity inhibited proliferation
      but did not protect HCD57 cells from apoptosis induced by EPO withdrawal.
      Treatment of HCD57 cells with tumor necrosis factor-alpha induced JNK activation
      but did not induce apoptosis. These results implicate JNK, p38, and ERK in EPO
      induced proliferation and/or survival of erythroid cells but do not support a
      role for JNK or p38 in apoptosis induced by EPO withdrawal from erythroid cells.

PMID- 10910908
TI  - A member of Forkhead family transcription factor, FKHRL1, is one of the
      downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in
      erythropoietin signal transduction.
AB  - The phosphatidylinositol 3-kinase (PI3K) signaling pathway is important for the
      regulation of a number of cellular responses. Serine/threonine kinase Akt
      (protein kinase B; PKB) is downstream of PI3K and activated by growth factors.
      This study found that erythropoietin (EPO) induced tyrosine phosphorylation of
      Akt in a time- and dose-dependent manner in EPO-dependent human leukemia cell
      line UT-7/EPO. In vitro kinase assay using histone H2B and glucose synthase
      kinase as substrates demonstrated that Akt was actually activated by EPO. EPO
      induced phosphorylation of Akt was completely blocked by a PI3K-specific
      inhibitor, LY294002, at 10 micromol/L, indicating that activation of Akt by EPO
      is dependent on PI3K activity. In addition, overexpression of the constitutively
      active form of Akt on UT-7/EPO cells partially blocked apoptosis induced by
      withdrawal of EPO from the culture medium. This finding suggested that the PI3K
      Akt activation pathway plays some role in the antiapoptotic effect of EPO. EPO
      induced phosphorylation of a member of the trancription factor Forkhead family,
      FKHRL1, at threonine 32 and serine 253 in a dose- and time-dependent manner in UT
      7/EPO cells. Moreover, results showed that Akt kinase activated by EPO directly
      phosphorylated FKHRL1 protein and that FKHRL1 phosphorylation was completely
      dependent on PI3K activity as is the case for Akt. In conjunction with the
      evidence that FKHRL1 is expressed in normal human erythroid progenitor cells and
      erythroblasts, the results suggest that FKHRL1 plays an important role in
      erythropoiesis as one of the downstream target molecules of PI3K-Akt.

PMID- 10910909
TI  - Mouse Jagged2 is differentially expressed in hematopoietic progenitors and
      endothelial cells and promotes the survival and proliferation of hematopoietic
      progenitors by direct cell-to-cell contact.
AB  - To study the regulation of the early stages of hematopoiesis, cDNA
      representational difference analysis was used to isolate genes that were
      differentially expressed in primitive hematopoietic progenitors. The reasoning
      was that such genes were more likely to provide functions important to
      hematopoietic stem cells and progenitors. One of the genes identified through
      this approach encodes mouse Jagged2 (mJagged2). Using quantitative reverse
      transcription-polymerase chain reaction, it was shown that mJagged2 was
      differentially expressed in c-kit(+) hematopoietic progenitors, including those
      with the phenotypes of Lin(-) c-kit(+) Rh(lo) Ho(lo) and Lin(-) c-kit(+) Rh(hi)
      Ho(lo), and that they have been shown to be highly enriched for long-term and
      short-term repopulating hematopoietic stem cells, respectively. Western blot
      analyses showed that endothelial cells also expressed high levels of Jagged2, but
      stromal fibroblasts did not. Using a coculture system we found that exogenous,
      full-length mJagged2 promoted the survival and proliferation of hematopoietic
      progenitors, including the high-proliferative potential colony-forming cells.
      Direct cell-to-cell contact was required for this effect. Taken together, these
      findings indicate that both c-kit(+) hematopoietic progenitors and endothelial
      cells express Jagged2 and that exogenous, full-length Jagged2 promotes the
      survival and proliferation of hematopoietic progenitors.

PMID- 10910910
TI  - A novel cause of mild/moderate hemophilia A: mutations scattered in the factor
      VIII C1 domain reduce factor VIII binding to von Willebrand factor.
AB  - The mechanisms responsible for the low factor VIII (fVIII) activity in the plasma
      of patients with mild/moderate hemophilia A are poorly understood. In such
      patients, we have identified a series of fVIII mutations (Ile2098Ser, Ser2119Tyr,
      Asn2129Ser, Arg2150His, and Pro2153Gln) clustered in the C1 domain and associated
      with reduced binding of fVIII to von Willebrand factor (vWf). For each patient
      plasma, the specific activity of mutated fVIII was close to that of normal fVIII.
      Scatchard analysis showed that the affinity for vWf of recombinant Ile2098Ser,
      Ser2119Tyr, and Arg2150His fVIII mutants was reduced 8-fold, 80-fold, and 3-fold,
      respectively, when compared with normal fVIII. Given the importance of vWf for
      the stability of fVIII in plasma, these findings suggested that the reduction of
      fVIII binding to vWf resulting from the above-mentioned mutations could
      contribute to patients' low fVIII plasma levels. We, therefore, analyzed the
      effect of vWf on fVIII production by Chinese hamster ovary (CHO) cells
      transfected with expression vectors for recombinant B domain-deleted normal,
      Ile2098Ser, Ser2119Tyr, and Arg2150His fVIII. These 3 mutations impaired the vWf
      dependent accumulation of functional fVIII in culture medium. Analysis of fVIII
      production by transiently transfected CHO cells indicated that, in addition to
      the impaired stabilization by vWf, the secretion of functional Ile2098Ser and
      Arg2150His fVIII was reduced about 2-fold and 6-fold, respectively, by comparison
      to Ser2119Tyr and normal fVIII. These findings indicate that C1-domain mutations
      resulting in reduced fVIII binding to vWf are an important cause of mild/moderate
      hemophilia A.

PMID- 10910912
TI  - A topological study of the human gamma-glutamyl carboxylase.
AB  - gamma-Glutamyl carboxylase (GC), a polytopic membrane protein found in the
      endoplasmic reticulum (ER), catalyzes vitamin K-dependent posttranslational
      modification of glutamate to gamma-carboxyl glutamate. In an attempt to delineate
      the structure of this important enzyme, in vitro translation and in vivo mapping
      were used to study its membrane topology. Using terminus-tagged full-length
      carboxylase, expressed in 293 cells, it was demonstrated that the amino-terminus
      of the GC is on the cytoplasmic side of the ER, while the carboxyl-terminus is on
      the lumenal side. In addition, a series of fusions were made to encode each
      predicted transmembrane domain (TMD) followed by a leader peptidase (Lep)
      reporter tag, as analyzed by the computer algorithm TOPPRED II. Following in
      vitro translation of each fusion in the presence of canine microsomes, the
      topological orientation of the Lep tag was determined by proteinase K digestion
      and endoglycosidase H (Endo H) cleavage. From the topological orientation of the
      Lep tag in each fusion, the GC spans the ER membrane at least 5 times, with its N
      terminus in the cytoplasm and its C-terminus in the lumen.

PMID- 10910911
TI  - Induction of monocyte tissue factor expression by homocysteine: a possible
      mechanism for thrombosis.
AB  - Moderately elevated plasma homocysteine levels are an important independent risk
      factor for arterial and venous thrombosis and for atherosclerosis. Some
      investigators have proposed that homocysteine's effects result from oxidant
      injury to the vascular endothelium or from an alteration in endothelial function.
      However, homocysteine may have other cellular targets. We now report that
      homocysteine, at physiologically relevant concentrations, induces the expression
      of tissue factor by monocytes. In response to homocysteine, monocytes express
      procoagulant activity in a dose-dependent and a time-dependent manner. This
      activity is attributable to tissue factor because it was dependent on factor VII
      and blocked by anti-tissue factor antibodies. Tissue factor mRNA levels were also
      increased in monocytes after homocysteine treatment. The effect was found to be
      specific because analogues of homocysteine (homocystine and homocysteine
      thiolactone) did not mimic homocysteine's activity, nor did other thiol compounds
      (cysteine, 2-mercaptoethanol, dithiothreitol). On the other hand, methionine, the
      metabolic precursor of homocysteine, was active though less potent than
      homocysteine. Catalase and superoxide dismutase (scavengers of H(2)O(2) and O(2)(
      ) Radicals, respectively) were unable to block the expression of tissue factor
      induced by homocysteine, as was a 5-fold excess of the reducing agent 2
      mercaptoethanol. We conclude that the induction of tissue factor expression by
      circulating monocytes is a plausible mechanism by which homocysteine may induce
      thrombosis and that a nonspecific redox process is not involved.

PMID- 10910913
TI  - Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to
      the 1.5-angstrom human C2-domain crystal structure.
AB  - Factor VIII C domains contain key binding sites for von Willebrand factor (vWF)
      and phospholipid membranes. Hemophilic patients were screened for factor VIII C
      domain mutations to provide a well-characterized series. Mutated residues were
      localized to the high-resolution C2 structure and to a homology model of C1. Of
      30 families found with mutations in the C domains, there were 14 missense
      changes, and 9 of these were novel. Of the missense mutations, 10 were associated
      with reduced vWF binding and 8 were at residues with surface-exposed side chains.
      Six of the 10 mutants had nearly equivalent factor VIII clotting activity and
      antigen level, suggesting that reduced vWF binding could cause hemophilia by
      reducing factor VIII stability in circulation. When the present series was
      combined with previously described mutations from an online international
      database, 11 C1 and C2 mutations in patients with mild or moderately severe
      hemophilia A were associated with antibody-inhibitor development in at least one
      affected individual. Of these substitutions, 6 occurred at surface-exposed
      residues. As further details of the C1 structure and its interface with C2 become
      available, and as binding studies are performed on the plasma of more patients
      with hemophilic C-domain mutations, prediction of surface binding sites should
      improve, allowing confirmation by site-specific mutagenesis of surface-exposed
      residues.

PMID- 10910914
TI  - The factor XIII V34L polymorphism accelerates thrombin activation of factor XIII
      and affects cross-linked fibrin structure.
AB  - Factor XIII on activation by thrombin cross-links fibrin. A common polymorphism
      Val to Leu at position 34 in the FXIII A subunit is under investigation as a risk
      determinant of thrombosis. Because Val34Leu is close to the thrombin cleavage
      site, the hypothesis that it would alter the function of FXIII was tested.
      Analysis of FXIII subunit proteolysis by thrombin using sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and high-performance liquid chromatography
      showed that FXIII 34Leu was cleaved by thrombin more rapidly and by lower doses
      than 34Val. Mass spectrometry of isolated activation peptides confirmed the
      predicted single methyl group difference and demonstrated that the thrombin
      cleavage site is unaltered by Val34Leu. Kinetic analysis of activation peptide
      release demonstrated that the catalytic efficiency (k(cat)/K(m)) of thrombin was
      0.5 for FXIII 34Leu and 0.2 (micromol/L)(-1) x sec(-1) for 34Val. Presence of
      fibrin increased the catalytic efficiency to 4.8 and 2.2 (micromol/L)(-1) x sec(
      1), respectively. Although the 34Leu peptide was released at a similar rate as
      fibrinopeptide A, the 34Val peptide was released more slowly than fibrinopeptide
      A but more quickly than fibrinopeptide B generation. Cross-linking of gamma- and
      alpha-chains appeared earlier when fibrin was incubated with FXIII 34Leu than
      with 34Val. Fully activated 34Leu and 34Val FXIII showed similar cross-linking
      activity. Analysis of fibrin clots prepared using plasma from FXIII 34Leu
      subjects by turbidity and permeability measurements showed reduced fiber
      mass/length ratio and porosity compared to 34Val. The structural differences were
      confirmed by electron microscopy. These results demonstrate that Val34Leu
      accelerates activation of FXIII by thrombin and consequently affects the
      structure of the cross-linked fibrin clot.

PMID- 10910915
TI  - Pharmacologic properties of P(2Z)/P2X(7 )receptor characterized in murine
      dendritic cells: role on the induction of apoptosis.
AB  - In the immune system, extracellular adenosine 5'-triphosphate (ATP) mediates a
      variety of effects mainly through activation of a particular receptor subtype,
      the pore-forming P(2Z)/P2X(7) purinoceptor. This purinergic receptor has been
      described chiefly in cells of hemopoietic origin such as T cells, thymocytes,
      monocytes, macrophages, and phagocytic cells of thymic reticulum. In this study,
      we characterized the P(2Z)/P2X(7) purinoceptor and the ATP-mediated apoptosis in
      murine spleen-derived dendritic cells (DCs). Dye uptake and apoptosis were
      evaluated by flow cytometry. ATP-treated DCs were permeable to different low
      molecular-weight fluorescent probes such as ethidium bromide, YO-PRO 1, and
      lucifer yellow. Such an effect was dose-dependent (EC(50): 721 micromol/L);
      mediated by the fully anionic agonist (ATP(4-)); and specifically stimulated by
      ATP, BzATP, and ATPgammaS. Additionally, an ATP-induced increase in intracellular
      calcium was detected by microfluorometry. Furthermore, ATP treatment induced a
      significant increase in apoptotic DCs (64. 46% +/- 3.8%) when compared with
      untreated control cells (34% +/- 5. 8%), as ascertained by the TdT-mediated dUTP
      nick end labeling technique. Both ATP-induced DC permeabilization and apoptosis
      were inhibited by oxidized ATP, a P(2Z)/P2X(7)-specific antagonist. In
      conclusion, we characterized the expression of the P(2Z)/P2X(7) purinoceptor in
      murine spleen-derived DCs and described its role on the induction of apoptosis.

PMID- 10910916
TI  - Interleukin-15 redirects the outcome of a tolerizing T-cell stimulus from
      apoptosis to anergy.
AB  - Clonal deletion and anergy are 2 mechanisms used by the immune system to
      establish peripheral tolerance. In vitro, these mechanisms are induced in T
      lymphocytes by triggering the T-cell receptor (signal 1) in the absence of
      costimulation (signal 2). T-cell clones have been shown either to become anergic
      or to die in response to signal 1 alone; yet the factors that govern this choice
      remain unknown. This study evaluated the influence of the cytokines interleukin
      (IL)-2 and IL-15 on the response of the Th1 clone hemagglutinin (T-HA) to signal
      1, delivered by stimulation with immobilized anti-CD3 monoclonal antibody (mAb).
      The response induced by immobilized anti-CD3 mAb was dependent on the cytokine
      milieu; in the presence of IL-2, T-HA cells were subject to apoptosis, whereas in
      the presence of IL-15 the cells remained viable but showed proliferative
      unresponsiveness. After release from the anti-CD3 stimulus, the IL-15-rescued T
      HA cells regained responsiveness to IL-2 and IL-15 growth factor activity.
      However, they were unable to proliferate when stimulated with their cognate
      antigen presented by professional antigen-presenting cells (signal 1 plus 2) and
      thus had acquired an anergic phenotype. These data assign a novel function to the
      previously reported antiapoptotic activity of IL-15, namely, the capacity to
      redirect the T-cell response to partial stimulation from clonal deletion to
      anergy. Furthermore, they emphasize that the cytokine environment can critically
      influence the outcome of a tolerizing stimulus.

PMID- 10910917
TI  - A-myb rescues murine B-cell lymphomas from IgM-receptor-mediated apoptosis
      through c-myc transcriptional regulation.
AB  - A-myb is a member of the myb family of transcription factors, which regulates
      proliferation, differentiation, and apoptosis of hematopoietic cells. A-Myb
      expression is normally restricted to the proliferating B-cell centroblasts and
      transgenic mice overexpressing A-myb displayed enhanced hyperplasia of the lymph
      nodes. Because A-Myb is highly expressed in several subtypes of human B-cell
      neoplasias, we sought to determine whether the A-myb gene promoted proliferation
      and survival of B lymphocytes, using the WEHI 231 and CH33 murine B-cell
      lymphomas as models. Here, we show that ectopic expression of A-myb rescues WEHI
      231 and CH33 cells from growth arrest and apoptosis induced by anti-IgM
      treatment. Previously, we demonstrated an essential role of the c-myc gene in
      promoting cell survival of WEHI 231 cells in response to a variety of apoptotic
      stimuli. Furthermore, we and others have shown that the c-myc gene is potently
      transactivated by A-Myb in several cell types. Thus, we sought to determine
      whether c-Myc would mediate the A-Myb antiapoptotic effect in B cells. Here we
      show that ectopic expression of A-myb leads to maintenance of c-myc expression,
      and that expression of antisense c-myc RNA ablates A-Myb-mediated survival
      signals. Thus, these findings strongly implicate the A-myb gene in the regulation
      of B-cell survival and confirm the c-myc gene as one of the downstream targets of
      A-myb in these cells. Overall, our observation suggests that A-myb expression may
      be relevant to the pathology of human B-cell neoplasias.

PMID- 10910918
TI  - CD3zeta and CD28 down-modulation on CD8 T cells during viral infection.
AB  - Down-modulation of CD3zeta expression on CD8 T lymphocytes occurs, independently
      of other T-cell receptor (TCR)-CD3 components, in tumor-infiltrating lymphocytes,
      human immunodeficiency virus infection, and autoimmune disease. These
      associations suggest that it might be related to chronic antigenic stimulation.
      CD3zeta down-modulation was found, however, in CD8 T cells that proliferate in
      response to acute viral infections. In 3 otherwise healthy donors with acute
      gastroenteritis, infectious mononucleosis, and Epstein-Barr
      virus/cytomegalovirus/mononucleosis, 30% to 60% of circulating CD8 T cells had
      down-modulated CD3zeta to below the level of detection. The CD3zeta-T cells were
      also CD28- but expressed the activation markers HLA-DR and CD57. CD3zeta-CD28- T
      cells are effector CTL because they express perforin and produce IFN-gamma, but
      not IL-2, on activation and contain the viral-specific cytotoxic T lymphocyte
      (CTL). However, CD3zeta-CD28-T cells generally do not express CD25 after anti-CD3
      and anti-CD28 stimulation and are not cytotoxic until they are cultured with IL-2
      overnight. Cytotoxicity coincides with the re-expression of CD3zeta but not CD28.
      Down-modulation of CD3zeta and CD28 on effector CTL may control CTL triggering
      and proliferation to prevent immunopathogenesis.

PMID- 10910919
TI  - Caspase-independent commitment phase to apoptosis in activated blood T
      lymphocytes: reversibility at low apoptotic insult.
AB  - Little is known about the mechanisms of programmed death triggered in T
      lymphocytes by stimuli that can bypass caspase activation. Anti-CD2 monoclonal
      antibody and staurosporine are such apoptosis inducers because they operate in
      the presence of broad-spectrum caspase inhibitors BOC-D.fmk and Z-VAD.fmk. A
      system was devised, based on the isolation according to density of activated
      blood T cells progressively engaged in the apoptotic process. This allowed
      definition of a sequence of caspase-dependent and caspase-independent apoptogenic
      events that are triggered by anti-CD2 and staurosporine. Thus, a commitment phase
      to apoptosis was defined that is entirely caspase independent and that is
      characterized by cell volume loss, partial chromatin condensation, and release
      into the cytosol and the nucleus of mitochondrial "apoptosis-inducing factor "
      (AIF). Committed cells were viable, displayed a high mitochondrial inner
      transmembrane potential (triangle upPsim), and lacked large-scale and
      oligonucleosomal DNA fragmentation. Mitochondrial release of AIF was selective
      because cytochrome c was retained in mitochondria of the very same cells.
      Mitochondrial release of cytochrome c occurred later, at the onset of the
      execution phase of apoptosis, concurrently with triangle upPsim collapse, poly
      (ADP-ribose) polymerase cleavage, and DNA fragmentation. The apoptogenic events
      of this commitment phase are reversible if the strength of the stimulus is low
      and of short duration.

PMID- 10910920
TI  - The PI3 kinase, p38 SAP kinase, and NF-kappaB signal transduction pathways are
      involved in the survival and maturation of lipopolysaccharide-stimulated human
      monocyte-derived dendritic cells.
AB  - As a dendritic cell (DC) matures, it becomes more potent as an antigen-presenting
      cell. This functional change is accompanied by a change in DC immunophenotype.
      The signal transduction events underlying this process are poorly characterized.
      In this study, we have investigated the signal transduction pathways involved in
      the lipopolysaccharide (LPS)-induced maturation of human monocyte-derived DCs
      (MoDCs) in vitro. We show that exposure of immature MoDCs to LPS activates the
      p38 stress-activated protein kinase (p38SAPK), extracellular signal-regulated
      protein kinase (ERK), phosphoinositide 3-OH kinase (PI3 kinase)/Akt, and nuclear
      factor (NF)-kappaB pathways. Studies using inhibitors demonstrate that PI3
      kinase/Akt but not the other pathways are important in maintaining survival of
      LPS-stimulated MoDCs. Inhibiting p38SAPK prevented activation of the
      transcription factors ATF-2 and CREB and significantly reduced the LPS-induced up
      regulation of CD80, CD83, and CD86, but did not have any significant effect on
      the LPS-induced changes in macropinocytosis or HLA-DR, CD40, and CD1a expression.
      Inhibiting the NF-kappaB pathway significantly reduced the LPS-induced up
      regulation of HLA-DR as well as CD80, CD83, and CD86. Inhibiting the p38SAPK and
      NF-kappaB pathways simultaneously had variable effects depending on the cell
      surface marker studied. It thus appears that different aspects of LPS-induced
      MoDC maturation are regulated by different and sometimes overlapping pathways.

PMID- 10910921
TI  - Differential use of FasL- and perforin-mediated cytolytic mechanisms by T-cell
      subsets involved in graft-versus-myeloid leukemia responses.
AB  - In graft-versus-leukemia (GVL) responses, the cellular subsets and effector
      mechanisms responsible for cytotoxicity against leukemic cells in vivo remain
      poorly characterized. A murine model of syngeneic GVL that features CD4(+) and
      CD8(+) T-cell responses against the MMB3.19 myeloid leukemia cell line has been
      previously described. MMB3.19 expresses high levels of functional Fas and tumor
      necrosis factor (TNF) receptors that do not transduce proapoptotic signals.
      Through the use of perforin- and Fas ligand (FasL)-deficient mice, it was
      demonstrated that CD4(+) T cells mediate anti-MMB3.19 effects in vivo primarily
      through the use of FasL and secondarily through perforin mechanisms. Conversely,
      CD8(+) T cells induce GVL effects primarily through the use of perforin and
      minimally through FasL mechanisms. Although the in vivo observations of CD8(+) T
      cells were reflective of their in vitro cytotoxic T lymphocyte (CTL) activity,
      for CD4(+) T cells, in vitro responses were dominated by the perforin pathway. In
      addition, the diminished capacity of T cells from perforin- and FasL-deficient
      mice to lyse MMB3.19 target cells appeared directly related to their deficient
      cytotoxic functions rather than to defects in activation because these cells were
      fully capable of mounting proliferative responses to the tumor cells. These
      findings demonstrate that GVL responses of T-cell subsets can involve
      preferential use of different cytotoxic mechanisms. In particular, these findings
      identify a role for both FasL-employing CD4(+) CTLs and the more novel perforin
      utilizing CD4(+) T-cell subset in responses against a myeloid leukemia.

PMID- 10910922
TI  - Functional characterization of an IL-7-dependent CD4(+)CD8alphaalpha(+) Th3-type
      malignant cell line derived from a patient with a cutaneous T-cell lymphoma.
AB  - CDR3 of the functional rearranged T-cell receptor variable beta region (TCR
      Vbeta) transcript was sequenced in order to demonstrate for the first time the
      identity between a long-term cultured T-cell line derived from a cutaneous T-cell
      lymphoma (CTCL) patient and the malignant T-cell clone present in the blood. The
      patient's peripheral blood lymphocyte-derived cultured T-cell line had a
      CD3(+)Vbeta22(+)CD4(+)CD8alphaalpha(+)CD25(-) phenotype. It was named Pno and had
      been cultured for more than 1 year. Both fresh and long-term-cultured tumor cells
      proliferated highly in response to interleukin-7 (IL-7), and exogeneous IL-7
      prevented Pno lymphocytes from apoptosis and maintained high levels of Bcl-2
      expression. This unique malignant cloned lymphocyte line was further used to
      carry out functional studies. The results indicated that the CD3/TCR structures
      expressed by the Pno lymphocytes were functional because an immobilized anti-CD3
      monoclonal antibody (mAb) or the combination of a soluble anti-CD3 mAb with
      submitogenic doses of phorbol 12 beta-myristate 13 alpha-acetate induced a
      proliferative response. Further, the CD2 and CD28 coreceptors were functional
      because they were able to induce a strong proliferative response upon their
      specific stimulation. Finally, the Pno T cell line had a Th3-type cytokine
      profile because it produced high amounts of the immunosuppressor cytokine tumor
      growth factor-beta1 (TGF-beta1). This high production of TGF-beta1 may inhibit
      antitumor specific responses in CTCL.

PMID- 10910923
TI  - B-cell-autonomous somatic mutation deficit following bone marrow transplant.
AB  - Hematopoietic stem cell transplantation is characterized by a prolonged period of
      humoral immunodeficiency. We have previously shown that the deficiencies are
      probably not due to the failure to utilize the appropriate V regions in the pre
      immune repertoire. However, a striking observation, which correlated with the
      absence of immunoglobulin IgD(-) cells and was consistent with a defect in
      antigen-driven responses, was that rearrangements in bone marrow transplant (BMT)
      recipients exhibited much less somatic mutation than did rearrangements obtained
      from healthy subjects. In this paper, we present evidence suggesting that naive B
      cells obtained from BMT recipients lack the capacity to accumulate somatic
      mutations in a T-cell-dependent manner compared with healthy subjects. This
      appears to be a B-cell-autonomous deficit because T cells from some patients,
      which were not able to support the accumulation of mutations in autologous naive
      B cells, were able to support accumulation of mutations in heterologous healthy
      subject naive B cells.

PMID- 10910924
TI  - Selection and characterization of BCR-ABL positive cell lines with differential
      sensitivity to the tyrosine kinase inhibitor STI571: diverse mechanisms of
      resistance.
AB  - Targeting the tyrosine kinase activity of Bcr-Abl with STI571 is an attractive
      therapeutic strategy in chronic myelogenous leukemia (CML). A few CML cell lines
      and primary progenitors are, however, resistant to this compound. We investigated
      the mechanism of this resistance in clones of the murine BaF/3 cells transfected
      with BCR-ABL and in 4 human cell lines from which sensitive (s) and resistant (r)
      clones were generated by various methods. Although the resistant cells were able
      to survive in the presence of STI571, their proliferation was approximately 30%
      lower than that of their sensitive counterparts in the absence of the compound.
      The concentration of STI571 needed for a 50% reduction in viable cells after a 3
      day exposure was on average 10 times higher in the resistant (2-3 micromol/L)
      than in the sensitive (0.2-0.25 micromol/L) clones. The mechanism of resistance
      to STI571 varied among the cell lines. Thus, in Baf/BCR-ABL-r, LAMA84-r, and
      AR230-r, there was up-regulation of the Bcr-Abl protein associated with
      amplification of the BCR-ABL gene. In K562-r, there was no Bcr-Abl
      overexpression, but the IC(50) for the inhibition of Bcr-Abl autophosphorylation
      was increased in the resistant clones. Sequencing of the Abl kinase domain
      revealed no mutations. The multidrug resistance P-glycoprotein (Pgp) was
      overexpressed in LAMA84-r, indicating that at least 2 mechanisms of resistance
      operate in this cell line. KCL22-r showed neither Bcr-Abl up-regulation nor a
      higher threshold for tyrosine kinase inhibition by STI571. We conclude that BCR
      ABL-positive cells can evade the inhibitory effect of STI571 by different
      mechanisms, such as Bcr-Abl overexpression, reduced intake mediated by Pgp, and,
      possibly, acquisition of compensatory mutations in genes other than BCR-ABL.

PMID- 10910925
TI  - Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their
      clinical implications in acute myelogenous leukemia.
AB  - A previous study reported that a nondifferentiating myeloid leukemia cell line
      produced differentiation-inhibiting factors. One of the factors was purified as a
      homologue of the nm23 genes. The nm23 genes were overexpressed in acute
      myelogenous leukemia (AML) cells, and a higher level of nm23 gene expression was
      correlated with a poor prognosis in AML. The present study determined the plasma
      levels of nm23-H1 protein by enzyme-linked immunosorbent assay and assessed the
      association between this level and the clinical outcome in 102 patients with AML.
      The plasma concentration of nm23-H1 was higher in patients with AML than in
      normal controls (P =.0001). Plasma nm23-H1 levels were correlated with the
      product of the intracellular nm23 messenger RNA (mRNA) level and the white blood
      cell count, but not with the mRNA level alone. Therefore, nm23-H1 plasma levels
      probably depend on the total mass of leukemic cells overexpressing the nm23-H1
      gene. Overall survival was lower in patients with higher plasma nm23-H1 levels
      than in those with lower levels. Multivariate analysis using the Cox proportional
      hazard model showed that elevated plasma nm23-H1 levels significantly contributed
      to the prognosis of AML patients. Furthermore, the plasma nm23-H1 levels were
      investigated in 70 patients with other hematologic neoplasms, including 6 with
      acute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 with
      myelodysplastic syndrome. Plasma nm23-H1 levels were significantly higher in all
      of these hematologic neoplasms than in normal controls. Increased plasma levels
      of nm23-H1 may have prognostic value in these hematologic malignancies as well as
      in AML.

PMID- 10910926
TI  - Molecular features responsible for the absence of immunoglobulin heavy chain
      protein synthesis in an IgH(-) subgroup of multiple myeloma.
AB  - This study involved 12 patients with multiple myeloma (MM), in whom malignant
      plasma cells did not contain immunoglobulin heavy chain (IgH) protein chains.
      Southern blot analysis revealed monoallelic J(H) gene rearrangements in 10
      patients, biallelic rearrangement in 1 patient, and biallelic deletion of the
      J(H) and C(micro) regions in 1 patient. Heteroduplex polymerase chain reaction
      analysis enabled the identification and sequencing of 9 clonal J(H) gene
      rearrangements. Only 4 of the joinings were complete V(H)-(D)-J(H)
      rearrangements, including 3 in-frame rearrangements with evidence of somatic
      hypermutation. Five rearrangements concerned incomplete D(H)-J(H) joinings,
      mainly associated with deletion of the other allele. Curiously, in at least 1 of
      these 5 cases the second allele seemed to be in germline configuration, whereas
      the in-frame V(kappa)-J(kappa) gene rearrangements contained somatic mutations.
      The configuration of the IGH genes was further investigated by use of C(H)
      probes. In 5 patients the rearrangements in the J(H) and C(H) regions were not
      concordant, probably caused by illegitimate IGH class switch recombination
      (chromosomal translocations to 14q32. 3). These data indicate that in many IgH(-)
      MM patients illegitimate IGH class switch rearrangement or illegitimate deletion
      of the functional V(H)-(D(H))-J(H) allele are responsible for IgH negativity. For
      example, the exclusive presence of D(H)-J(H) rearrangements in combination with
      mutated IGK genes can only be explained in terms of normal B-cell development, if
      the second (functional) IGH allele is deleted, which was probably the case in
      most patients. Therefore, defects at the DNA level are responsible for the lack
      of IgH protein production in most IgH(-) MM patients.

PMID- 10910927
TI  - TEL/AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase
      in childhood acute lymphoblastic leukemia.
AB  - The t(12;21) translocation resulting in TEL/AML1 gene fusion is present in
      approximately 25% of patients with precursor B-lineage pediatric acute
      lymphoblastic leukemia (ALL). Studies suggest an association with a good
      prognosis; however, relapse can occur. We studied the relation between t(12;21),
      determined by fluorescence in situ hybridization or polymerase chain reaction,
      and in vitro drug resistance, measured by the MTT assay, in childhood B-lineage
      ALL at diagnosis. A total of 180 ALL samples were tested, 51 (28%) of which were
      positive for t(12;21). The median LC(50) values did not differ significantly
      between TEL/AML1-positive and -negative samples for prednisolone, dexamethasone,
      daunorubicin, thiopurines, epipodophyllotoxins, and 4-HOO-ifosfamide. However,
      the TEL/AML1-positive patients were relatively more sensitive to L-asparaginase
      (ASP; 5.9-fold; P =.029) and slightly but significantly more resistant to
      vincristine (1.5-fold; P =.011) and cytarabine (1.5-fold; P =.014). After
      matching for unevenly distributed patient characteristics-that is, excluding
      patients younger than 12 months, patients with CD10-negative immature B-lineage
      ALL, patients with Philadelphia chromosome, and patients who were hyperdiploid
      (more than 50 chromosomes) from the TEL/AML1 negative group-the only remaining
      difference was a relative sensitivity for ASP in the TEL/AML1-positive samples
      (10.8-fold; P =. 012). In conclusion, the presence of TEL/AML1 gene fusion in
      childhood precursor B-lineage ALL does not seem to be associated with a high in
      vitro drug sensitivity, except for ASP, indicating that these patients could
      benefit from treatment schedules with significant use of this drug.

PMID- 10910928
TI  - LSP1 modulates the locomotion of monocyte-differentiated U937 cells.
AB  - To examine the effect of lymphocyte specific protein 1 (LSP1) on phagocytic cell
      motility, stable transfection of LSP1-null U937 cell line with an episomal
      expression vector carrying the LSP1 complementary DNA created lines expressing
      varied LSP1 levels. Mock transfectants without LSP1 (U937(-)) and cell lines with
      LSP1 levels similar to those of monocytes (U937(+)) or 4-fold those of monocytes
      (U937(+)) express LSP1 as indicated and express other actin-binding proteins at
      normal levels before or after monocytic induction (MI) with dibutyryl cyclic
      adenosine monophosphate. The cell lines were compared for rate of growth and cell
      division and, after monocytic differentiation, were video-tracked to measure
      locomotion as distance moved in 2 hours and examined for morphologic changes.
      Rates of cell division and growth were similar for different U937 cell lines at
      all LSP1 levels. In contrast, mean rate of locomotion (micrometers moved in 2
      hours) was slower in MI-U937( +) (7.78 + 1.11 microm, n = 3) and MI-U937(-)
      (23.89 + 2.78 microm, n = 3) than in MI-U937(+) cells (50.77 + 4.11 microm, n =
      3). Compared with MI-U937(-), the locomotive histogram (n = 150 cells) of MI
      U937(+) or MI-U937( +) cells shows all cells move respectively faster or slower
      as an entire cell population. In LSP1(+) U937 phagocytes, high LSP1 levels
      inhibit some (locomotion) but not all (cytokinesis) cell motile behaviors and
      cause the formation of surface projections. In contrast, normal LSP1 levels in
      U937 phagocytes enhance some (locomotion) but not all (cytokinesis) cellular
      motile behaviors and have no effect on cell morphology. Therefore, LSP1 level has
      a unique biphasic effect on cellular locomotion. The data suggest LSP1 is an
      important regulator of phagocyte locomotion.

PMID- 10910929
TI  - Molecular analysis of 9 new families with chronic granulomatous disease caused by
      mutations in CYBA, the gene encoding p22(phox).
AB  - Chronic granulomatous disease is a rare inherited disorder caused by nonexistent
      or severely decreased phagocyte superoxide production that results in a severe
      defect in host defense and consequent predisposition to microbial infection. The
      enzyme responsible for generating the superoxide, NADPH oxidase, involves at
      least 5 protein components. The absence of, or a defect in, any 1 of 4 of these
      proteins (p22(phox), p47(phox), p67(phox), or gp91(phox)) gives rise to the known
      types of chronic granulomatous disease. One of the rarest forms of the disease is
      due to defects in the CYBA gene encoding p22(phox), which together with
      gp91(phox) forms flavocytochrome b(558), the catalytic core of NADPH oxidase. To
      date, only 9 kindreds with p22(phox) deficiency have been described in the
      literature comprising 10 mutant alleles. Four polymorphisms in the CYBA gene have
      also been reported. Here we describe 9 new, unrelated kindreds containing 12
      mutations, 9 of which are novel. In addition, we report 3 new polymorphisms. The
      novel mutations are (a) deletion of exons 2 and 3, (b) a missense mutation in
      exon 3 (T155-->C), (c) a splice site mutation at the 5' end of intron 3, (d) a
      missense mutation in exon 2 (G74-->T), (e) a nonsense mutation in exon 1 (G26-
      >A), (f) a missense mutation in exon 4 (C268-->T), (g) a frameshift in exon 3 due
      to the insertion of C at C162, (h) a nonsense mutation in exon 2 (G107-->A), and
      (i) a missense mutation in exon 2 (G70-->A).

PMID- 10910930
TI  - The molecular defect in hypotransferrinemic mice.
AB  - Hypotransferrinemic (Trf(hpx/hpx)) mice have a severe deficiency in serum
      transferrin (Trf) as the result of a spontaneous mutation linked to the murine
      Trf locus. They are born alive, but before weaning, die from severe anemia if
      they are not treated with exogenous Trf or red blood cell transfusions. We have
      determined the molecular basis of the hpx mutation. It results from a single
      point mutation, which alters an invariable nucleotide in the splice donor site
      after exon 16 of the Trf gene. No normal Trf messenger RNA (mRNA) is made from
      the hpx allele. A small amount of mRNA results from the usage of cryptic splice
      sites within exon 16. The predominant cryptic splice site produces a Trf mRNA
      carrying a 27-base pair (bp), in-frame deletion. Less than 1% of normal levels of
      a Trf-like protein is found in the serum of Trf(hpx/hpx) mice, most likely
      resulting from translation of the internally deleted mRNA. Despite their severe
      Trf deficiency, however, Trf(hpx/hpx) mice initially treated with transferrin
      injections can survive after weaning without any further treatment. They have
      massive tissue iron overload develop in all nonhematopoietic tissues, while they
      continue to have severe iron deficiency anemia. Their liver iron burden is 100
      fold greater than that of wild-type mice and 15- to 20-fold more than that of
      mice lacking the hemochromatosis gene, Hfe. Trf(hpx/hpx) mice thus provide an
      additional model with a defined molecular defect for the study of genetic iron
      disorders.

PMID- 10910931
TI  - Fetal hemoglobin in sickle cell disease: relationship to erythrocyte
      phosphatidylserine exposure and coagulation activation.
AB  - In sickle cell disease (SCD), loss of erythrocyte membrane phospholipid asymmetry
      occurs with the exposure of phosphatidylserine (PS), which provides a docking
      site for coagulation proteins. In vivo sickling/desickling, with resulting red
      cell membrane changes and microvesicle formation, appears to be one of the
      factors responsible for PS exposure. We evaluated children with SCD homozygous
      for sickle hemoglobin (SS disease) and controls (n = 65) and demonstrate that
      high levels of fetal hemoglobin (assessed as F cells) are associated with
      decreased microvesicle formation, PS exposure, and thrombin generation. F cells
      correlated inversely with both microvesicles and PS positivity (P <.000001) in SS
      disease. Multiple regression analyses using various hematologic parameters as
      independent variables, and either microvesicles or PS positivity as the dependent
      variable, showed a strong relationship only with F cells. Additionally, plasma
      prothrombin fragment F1.2 levels (a marker for thrombin generation) correlated
      with both PS positivity (P <.001) and F cells (P <.01). An F-cell level of
      approximately 70% was associated with normal levels of prothrombin fragment F1.2
      and with microvesicle formation indistinguishable from control values. We suggest
      that the use of such surrogate biologic markers in conjunction with F-cell
      numbers may provide valuable insights into the biology and consequences of in
      vivo sickling.

PMID- 10910933
TI  - Triose phosphate isomerase deficiency in 3 French families: two novel null
      alleles, a frameshift mutation (TPI Alfortville) and an alteration in the
      initiation codon (TPI Paris).
AB  - Three French families with triose phosphate isomerase (TPI) deficiency were
      studied, and 2 new mutations giving rise to null alleles were observed: a
      frameshift mutation with deletion of the 86-87 TG dinucleotide in codon 29 (TPI
      Alfortville) and a T-->A transversion in nucleotide 2 of the initiation codon
      (TPI Paris). The first mutation occurred in compound heterozygosity with the
      frequent E105D mutation. The second mutation occurred in association with the 2
      nucleotide promoter variant (-43G,-46A). In a third family, the propositus was an
      E105D homozygote. In the TPI Paris family, the coinheritance of the -43,-46
      promoter variant appeared to exert little, if any, effect on TPI enzyme activity,
      a finding consistent with 2 previous reports that questioned the putative role of
      the promoter polymorphism as a true deficiency variant. Similarly, the further
      coinheritance of glucose-6-phosphate dehydrogenase (G6PD) A- (202 G-->A/376 A-
      >G) appeared to have little effect on the observed phenotype. Compound
      heterozygosity for the E105D mutation with the null allele TPI Alfortville
      appeared to lead to a more severe clinical syndrome than did E105D homozygosity,
      suggesting that compound heterozygosity with null alleles may lead to more
      profound clinical abnormalities than homozygosity with missense alleles. A
      simple, rapid polymerase chain reaction and restriction enzyme procedure for the
      E105D mutation was developed for prenatal diagnosis in one family and
      subsequently used for screening in the other families.

PMID- 10910932
TI  - Wild-type HFE protein normalizes transferrin iron accumulation in macrophages
      from subjects with hereditary hemochromatosis.
AB  - Hereditary hemochromatosis (HC) is one of the most common single-gene hereditary
      diseases. A phenotypic hallmark of HC is low iron in reticuloendothelial cells in
      spite of body iron overload. Most patients with HC have the same mutation, a
      change of cysteine at position 282 to tyrosine (C282Y) in the HFE protein. The
      role of HFE in iron metabolism and the basis for the phenotypic abnormalities of
      HC are not understood. To clarify the role of HFE in the phenotypic expression of
      HC, we studied monocytes-macrophages from subjects carrying the C282Y mutation in
      the HFE protein and clinically expressing HC and transfected them with wild-type
      HFE by using an attenuated Salmonella typhimurium strain as a gene carrier. The
      Salmonella system allowed us to deliver genes of interest specifically to
      monocytes-macrophages with high transduction efficiency. The accumulation of
      (55)Fe delivered by (55)Fe-Tf was significantly lower in macrophages from
      patients with HC than from controls expressing wild-type HFE. Transfection of HC
      macrophages with the HFE gene resulted in a high level of expression of HFE
      protein at the cell surface. The accumulation of (55)Fe delivered by (55)Fe-Tf
      was raised by 40% to 60%, and this was reflected by an increase in the (55)Fe
      ferritin pool within the HFE-transfected cells. These results suggest that the
      iron-deficient phenotype of HC macrophages is a direct effect of the HFE
      mutation, and they demonstrate a role for HFE in the accumulation of iron in
      these cells.

PMID- 10910934
TI  - The human ankyrin-1 gene is selectively transcribed in erythroid cell lines
      despite the presence of a housekeeping-like promoter.
AB  - To begin to study the sequence variations identified in the 5' flanking genomic
      DNA of the ankyrin gene in ankyrin-deficient hereditary spherocytosis patients
      and to provide additional insight into our understanding of the regulation of
      genes encoding erythrocyte membrane proteins, we have identified and
      characterized the erythroid promoter of the human ankyrin-1 gene. This compact
      promoter has characteristics of a housekeeping gene promoter, including very high
      G+C content and enzyme restriction sites characteristic of an HTF-island, no
      TATA, InR, or CCAAT consensus sequences, and multiple transcription initiation
      sites. In vitro DNAseI footprinting analyses revealed binding sites for GATA-1,
      CACCC-binding, and CGCCC-binding proteins. Transfection of ankyrin
      promoter/reporter plasmids into tissue culture cell lines yielded expression in
      erythroid, but not muscle, neural, or HeLa cells. Electrophoretic mobility shift
      assays, including competition and antibody supershift experiments, demonstrated
      binding of GATA-1, BKLF, and Sp1 to core ankyrin promoter sequences. In
      transfection assays, mutation of the Sp1 site had no effect on reporter gene
      expression, mutation of the CACCC site decreased expression by half, and mutation
      of the GATA-1 site completely abolished activity. The ankyrin gene erythroid
      promoter was transactivated in heterologous cells by forced expression of GATA-1
      and to a lesser degree BKLF.

PMID- 10910935
TI  - Recipient elimination of allogeneic lymphoid cells: donor CD4(+) cells are
      effective alloantigen-presenting cells.
AB  - The encounter with allogeneic major histocompatibility complex (MHC) molecules
      expressed on donor leukocytes during transfusion of blood products has been shown
      to impact the recipient's immune responses in a number of settings. To better
      understand the responses induced by the transfer of allogeneic cells, a murine
      model was used to characterize the recipient responses that control the fate of
      the allogeneic lymphoid cells. Recipient CD8(+) cells could rapidly eliminate a
      large number of donor cells within 3 days after injection. When elimination
      responses were studied in the absence of CD8(+) cells, it was found that
      alloantibody production was the secondary elimination mechanism. Optimal
      recipient CD8(+) and B cell responses in this model required help from CD4(+)
      cells that could be provided by 3 different pathways. Although recipient CD4(+)
      cells could provide help when activated by direct recognition of allogeneic MHC
      class II molecules expressed on donor cells or by indirect recognition of
      processed alloantigen presented on recipient antigen-presenting cells (APCs), the
      most rapid recipient responses were generated by help provided by donor CD4(+)
      cells. Purified donor CD4(+) cells were also able to induce these rapid
      responses, indicating that activated donor CD4(+) cells expressing allogeneic MHC
      molecules were able to effectively stimulate responses by both recipient CD8(+)
      and B cells.

PMID- 10910936
TI  - Graft-versus-host disease and donor-directed hemagglutinin titers after ABO
      mismatched related and unrelated marrow allografts: evidence for a graft-versus
      plasma cell effect.
AB  - The gradual disappearance of host antidonor isohemagglutinins after major ABO
      mismatched hematopoietic stem cell (HSC) allografts has been attributed to the
      gradual destruction of host plasma cells by graft-versus-host effects. To
      corroborate this hypothesis, we retrospectively analyzed results from 383 major
      or major/minor ABO-mismatched unrelated and related HSC allografts performed
      between 1983 and 1998. All patients were conditioned by high-dose pretransplant
      therapy and given methotrexate/cyclosporine for graft-versus-host disease (GvHD)
      prophylaxis. Of the 383 patients, 155 had HLA-matched related and 228 had
      unrelated grafts. We asked whether unrelated recipients experienced a more rapid
      disappearance of isohemagglutinins than related recipients, and whether, within
      the groups of related and unrelated recipients, the titer disappeared faster in
      patients with GvHD than in those without GvHD. The median time to reach
      undetectable antidonor IgG and IgM titers was significantly shorter in unrelated
      recipients (46 versus 61 days; P =.016). In addition, related recipients with
      GvHD had a 2. 2-fold increased likelihood (1.12-4.39,95% CI; P =.02) of reaching
      undetectable titers within 100 days than patients without GvHD. The persistence
      of antidonor isohemagglutinins led to significantly increased red blood cell
      (RBC) transfusion requirements in the ABO-mismatched related patients compared
      with ABO-matched counterparts. However, time to neutrophil and platelet
      engraftment, incidence of GvHD, and survival were not influenced by ABO
      incompatibility. In conclusion, our results corroborate the hypothesis that the
      rate of disappearance of antidonor isohemagglutinins after ABO-mismatched
      allogeneic HSC grafts is influenced by the degree of genetic disparity between
      donor and recipient, suggesting a graft-versus-plasma cell effect.

PMID- 10910937
TI  - Molecular modification of a recombinant anti-CD3epsilon-directed immunotoxin by
      inducing terminal cysteine bridging enhances anti-GVHD efficacy and reduces organ
      toxicity in a lethal murine model.
AB  - Immunotoxin (IT) therapy shows potential for selectively eliminating GVHD-causing
      T cells in vivo, but the field has been hampered by toxicity. Previously, we
      showed that a genetically engineered IT consisting of a single-chain protein,
      including the anti-CD3sFv spliced to a portion of diphtheria-toxin (DT(390)) has
      anti-GVHD effects, but pronounced organ toxicity common to this class of agent. A
      recombinant DT(390) anti-CD3sFv protein previously shown to have anti-GVHD
      activity was modified to reduce its filtration into kidney by genetically
      inserting a cysteine residue downstream of the sFv moiety at the c-terminus of
      the protein. This modification produced an intermolecular disulfide bridge,
      resulting in a bivalent, rather than a monovalent IT, termed SS2, that
      selectively inhibited T-cell proliferation in vitro. Although monomer and SS2
      were similar in in vitro activity, SS2 had a superior therapeutic index in vivo
      with at least 8-fold more being tolerated with reduced kidney toxicity. Most
      importantly, in a lethal model of GVHD, 40 microg SS2 given for 1 day, protected
      100% of the mice from lethal GVHD for 3 months, whereas the maximum tolerated
      dose (MTD) of monomer protected only 33%. To our knowledge, this is the first
      time disulfide bonded ITs have been created in this way and this simple molecular
      modification may address several problems in the IT field because it (1) markedly
      increased efficacy curing mice of GVHD after a single daily treatment, (2)
      markedly decreased organ toxicity, (3) increased the tolerated dosage, and (4)
      created a therapeutic window where none existed before.

PMID- 10910938
TI  - A novel application of cyclosporine A in nonmyeloablative pretransplant host
      conditioning for allogeneic BMT.
AB  - The treatment of mice with anti-CD4 and anti-CD8 monoclonal antibodies (mAbs) on
      day -5, plus 3 Gy whole body irradiation (WBI) and 7 Gy thymic irradiation (TI)
      on day 0, allows fully major-histocompatibility-complex-mismatched allogeneic
      bone marrow engraftment and the induction of immunologic tolerance. TI is
      required in this model to overcome alloreactivity and possibly to make "space" in
      the recipient thymus so that lasting central tolerance can be achieved. In
      addition to suppressing mature T cells in the periphery, Cyclosporine A (CYA) and
      glucocorticoids have a powerful influence on the thymus. In this study, we
      evaluated whether the administration of CYA to recipient mice for 12 days prior
      to bone marrow transplant (BMT), of glucocorticosteroids on the day of BMT, or a
      combination of both, could create space and overcome alloresistance in the thymus
      by specifically depleting immature and mature thymocytes prior to BMT. High
      levels of multilineage donor hematopoietic repopulation and specific
      transplantation tolerance were achieved in mice treated from days -15 to -3 with
      CYA (20 mg/kg/d subcutaneously), anti-CD4/CD8 mAbs on day -5, followed by 3 Gy
      WBI and 15 x 10(6) allogeneic bone marrow cells on day 0. Vbeta analysis
      suggested a central deletional tolerance mechanism. The same treatment without
      CYA pretreatment allowed only transient chimerism, without tolerance.
      Corticosteroid treatment abolished the engraftment-promoting and tolerance
      inducing effects of CYA. These results demonstrate a novel pretransplantation
      only application of CYA, which facilitates allogeneic marrow engraftment with
      minimal conditioning, by creating thymic space and/or overcoming intrathymic
      alloresistance.

PMID- 10910940
TI  - alpha-fibrinogen Thr312Ala polymorphism and venous thromboembolism.
AB  - The Aalpha-fibrinogen Thr312Ala polymorphism, which occurs in a region involved
      in factor XIII (FXIII)-dependent cross-linking processes, is associated with
      poststroke mortality in subjects with atrial fibrillation, suggesting an
      influence either on intraatrial clot formation or embolization. We have
      determined the association of Thr312Ala with deep vein thrombosis (DVT) and
      pulmonary embolism (PE) and have assessed the interaction of Thr312Ala with the
      FXIII Val34Leu polymorphism in 122 patients with DVT, 99 patients with PE, and
      254 healthy control subjects. The genotype distribution of patients with PE (TT =
      49%, TA = 36%, AA = 15%), but not DVT (TT = 50%, TA = 42%, AA = 8%), differed
      significantly from healthy control subjects (TT = 60%, TA = 34%, AA = 6%, P
      =.02). A significant interaction of Thr312Ala and Val34Leu was also identified (P
      =.01), indicating an inverse association between Leu34 and Ala312. These results
      support the hypothesis that Thr312Ala alters FXIII-dependent cross-linking,
      making formed fibrin clot more susceptible to embolization.

PMID- 10910939
TI  - Therapeutic levels of human factor VIII and IX using HIV-1-based lentiviral
      vectors in mouse liver.
AB  - Lentiviral vectors have the potential to play an important role in hemophilia
      gene therapy. The present study used human immunodeficiency virus (HIV)-based
      lentiviral vectors containing an EF1alpha enhancer/promoter driving human factors
      VIII (hFVIII) or IX (hFIX) complementary DNA expression for portal vein injection
      into C57Bl/6 mice. Increasing doses of hFIX-expressing lentivirus resulted in a
      dose-dependent, sustained increase in serum hFIX levels up to approximately 50-60
      ng/mL. Partial hepatectomy resulted in a 4- to 6-fold increase (P < 0.005) in
      serum hFIX of up to 350 ng/mL compared with the nonhepatectomized counterparts.
      The expression of plasma hFVIII reached 30 ng/mL (15% of normal) but was
      transient as the plasma levels fell concomitant with the formation of anti-hFVIII
      antibodies. However, hFVIII levels were persistent in immunodeficient C57Bl/6
      scid mice, suggesting humoral immunity-limited gene expression in immunocompetent
      mice. This study demonstrates that lentiviral vectors can produce therapeutic
      levels of coagulation factors in vivo, which can be enhanced with hepatocellular
      proliferation.

PMID- 10910941
TI  - Splenectomy selectively affects the distribution and mobility of the
      recirculating lymphocyte pool.
AB  - The spleen plays a major role in immune surveillance, but the impact that
      splenectomy exerts on the immune competence of an individual is not fully
      resolved. Here we show that neonatal splenectomy in sheep does not abrogate the
      development of a large, nonrecirculating pool of lymphocytes and that it has no
      effect on the acquisition of a normal blood lymphocyte profile. Splenectomy did,
      however, result in a significant decrease in blood residency time of
      recirculating lymphocytes and in an enhanced accumulation of recirculating
      lymphocytes in lymph nodes. Furthermore, nonrecirculating peripheral blood
      lymphocytes were less likely to migrate to the lung, possibly because of
      saturation of the marginal pool by recirculating lymphocytes. Although
      splenectomy has little effect on the development or distribution of lymphocyte
      subsets in blood and lymph, it has marked effects on the rate of recirculation of
      lymphocytes, which may have significant implications for peripheral immune
      surveillance in patients who undergo splenectomy.

PMID- 10910942
TI  - Pure red cell aplasia due to parvovirus B19 in a patient treated with rituximab.
AB  - Rituximab is a chimeric monoclonal antibody directed against CD20 and used in the
      treatment of B-cell non-Hodgkin's lymphoma. Due to its ability to deplete B
      lymphocytes, rituximab can interfere with humoral immunity, causing it to be
      suppressed for several months after treatment. The reported case depicts a
      serious consequence of this effect of rituximab therapy: pure red cell aplasia
      resulting from chronic parvovirus B19 infection. The point of interest in this
      case is not only the association between rituximab therapy and pure red cell
      aplasia, but the diagnostic and therapeutic utility of the knowledge of
      parvovirus B19 as the likely etiologic link between the two. Given the known
      efficacy of intravenous immunoglobulin (IVIg) in the treatment of chronic
      parvovirus B19 infection, this therapy can cure some of these patients and
      successfully render most others transfusion-independent until recovery of their
      own humoral immune system.

PMID- 10910943
TI  - Ligation of the CD44 adhesion molecule inhibits drug-induced apoptosis in human
      myeloid leukemia cells.
AB  - Adhesion molecules can improve hematopoietic cell survival; however, their role
      in leukemic cell resistance to drug-induced apoptosis is poorly documented. The
      CD44 adhesion molecule is strongly expressed on acute myeloid leukemia (AML)
      blasts. Using 2 myeloid cell lines, HL60 and NB4, evidence is presented that
      prior incubation with the CD44-specific monoclonal antibody (mAb) A3D8, reported
      to induce differentiation of AML blasts, significantly decreases apoptosis
      induced by 3 drugs used in AML chemotherapy: daunorubicin (DNR), mitoxantrone,
      and etoposide. In addition, in HL60 cells, CD44 ligation with A3D8 mAb fully
      abrogates the DNR-triggered generation of ceramide, a lipid second messenger
      involved in the DNR apoptotic signaling pathway. Moreover, results show that the
      A3D8 mAb and Bcl-2 additively inhibit DNR-induced apoptosis in HL60 cells
      overexpressing Bcl-2. These results suggest that, to eradicate AML blasts, the
      differentiation-inducing anti-CD44 mAb A3D8 should not be administered prior to
      apoptosis-inducing drugs.

PMID- 10910944
TI  - Familial thrombophilia associated with fibrinogen paris V: Dusart syndrome.
AB  - We report on a family with a history of venous thromboembolism associated with
      fibrinogen Paris V (fibrinogen Aalpha-Arg554-->Cys). Ten members experienced
      thrombotic events, including 4 with fatal pulmonary emboli. Pulmonary embolism
      was the presenting feature in 4. Those with the mutation and a history of
      thrombosis had somewhat higher fibrinogen concentrations than those with the
      mutation and no thrombosis (294 +/- 70 mg/dL vs 217 +/- 37 mg/dL, respectively).
      The Paris V mutation consistently caused a prolongation of the reptilase time,
      and fibrin clots containing the abnormal fibrinogen were more translucent than
      normal clots. Given the early onset of symptoms and the initial presentation with
      pulmonary embolism in some family members, it was justifiable to offer
      prophylactic anticoagulation with warfarin to carriers of the mutation.
      Fibrinogen Paris V has now been reported in 4 apparently unrelated families,
      indicating that it is a relatively common cause of dysfibrinogenemia-associated
      thrombosis.

PMID- 10910945
TI  - Identification of tamoxifen-DNA adducts in the endometrium of women treated with
      tamoxifen.
AB  - The risk of developing endometrial cancer increases significantly for women
      treated with tamoxifen (TAM); the present study was designed to investigate the
      mechanism of this carcinogenic effect. Endometrial tissue was obtained from 16
      women treated for varying lengths of time with TAM and from 15 untreated control
      subjects. DNA was analyzed with a (32)P-post-labeling/HPLC on-line monitoring
      assay capable of detecting 2.5 adducts/10(10) nucleotides. Using this sensitive
      and specific assay, TAM-DNA adducts were detected in eight women. The major
      adducts found were trans and cis epimers of alpha-(N(2)-deoxyguanosinyl)
      tamoxifen (dG-N(2)-TAM); levels ranged between 0.2-12 and 1.6-8.3 adducts/10(8)
      nucleotides, respectively. There was marked inter-individual variation in the
      relative amounts of cis and trans adducts present. Low levels (0.74-1.1
      adducts/10(8) nucleotides) of trans and cis forms of dG-N(2)-TAM N-oxide were
      detected in one patient. DNA adducts derived from 4-hydroxytamoxifen quinone
      methide were not observed. We conclude from this analysis that trans and cis dG
      N(2)-TAMs accumulate in significant amounts in the endometrium of many, but not
      all, women treated with this drug. The level of adducts found, coupled with the
      previous demonstration of their mutagenicity [Cancer Res., 59, 2091, 1999],
      suggest that a genotoxic mechanism may be responsible for TAM-induced endometrial
      cancer.

PMID- 10910946
TI  - Chemoprevention of biliary carcinogenesis in syrian hamsters by the novel
      carboxamide derivative IS-741 after initiation with N-nitrosobis(2
      oxopropyl)amine (BOP).
AB  - To elucidate the possible inhibitory effect of a novel carboxamide derivative (IS
      741) on biliary carcinogenesis, Syrian hamsters were subjected to
      cholecystoduodenostomy and ligation of the distal end of the common duct, and
      then given a regular diet (group I) or a diet containing 200 p.p.m. of IS-741
      (group II). All hamsters were subcutaneously injected with N-nitrosobis(2
      oxopropyl)amine until 10 weeks after surgery, and continued to feed on their
      respective dietary regimen until termination of the experiment at 16 weeks after
      surgery. Biliary adenocarcinomas were evaluated histologically. Non-cancerous and
      cancerous hepatobiliary tract tissues were analyzed for phospholipase A(2)
      (PLA(2)) activity, myeloperoxidase (MPO) activity, and the concentrations of
      prostaglandin (PG), i.e., prostaglandin E(2), 6-ketoprostaglandin F(1)alpha and
      thromboxane B(2). IS-741 significantly inhibited the development and multiplicity
      of hepatobiliary adenocarcinomas and reduced the proliferating cell nuclear
      antigen labeling indices in non-cancerous hepatobiliary tissues, compared with
      group I. The anti-cancerous effect of IS-741 was associated with a significant
      inhibition of PLA(2) and MPO levels in non-cancerous tissues of the extrahepatic
      biliary tract and the liver, and in cancerous tissue of the liver. Furthermore,
      IS-741 reduced the production of PGs in non-cancerous hepatobiliary tissues,
      compared with group I. Although the precise mechanism of action of IS-741 in
      preventing biliary tumorigenesis remains to be elucidated, it is likely to be
      related to modulation of arachidonic acid metabolism and/or suppression of
      neutrophil accumulation.

PMID- 10910947
TI  - 3-Methylcholanthrene triggers the differentiation of alveolar tumor cells from
      canine bronchial basal cells and an altered p53 gene promotes their clonal
      expansion.
AB  - Alveolar type II cells arising in canine bronchial autografts following exposure
      to 3-methylcholanthrene (MCA) give rise to carcinomas of varying glandular and
      squamous growth patterns. To study the role of the tumor suppressor gene p53 in
      this process, sections from progressive lesions were immunostained for p53
      protein; microdissected regions were screened for p53 mutations. Adjacent
      sections were examined for type II cell expression [cuboid cell shape, large
      roundish nucleus, cytoplasmic staining for surfactant protein A (SP-A)] and
      proliferating cell nuclear antigen expression. Evidence for an altered p53
      function (nuclear staining, missense mutations) was found in most carcinomas of
      all histologic types and in all grades of bronchial dysplasia, but not in
      hyperplastic or normal bronchial epithelium. It was primarily associated with the
      hyperplastic type II cell populations present in the basal zone of the lesions.
      In addition, we found SP-A staining in hyperplastic (but not in normal) bronchial
      basal cells. These data suggest that MCA initiates type II cell differentiation
      through phenotypic selection (basal cells). Inactivation of the p53 gene promotes
      the clonal expansion of the type II cells into discernible populations of
      (squamous or glandular) alveolar tumor cells. This in vivo study is the first to
      show that p53 is involved in a specific pathway leading to bronchogenic
      carcinoma.

PMID- 10910948
TI  - Hydroquinone, a benzene metabolite, increases the level of aneusomy of
      chromosomes 7 and 8 in human CD34-positive blood progenitor cells.
AB  - Benzene is an established human carcinogen, producing leukemia, hematotoxicity
      and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its
      conversion to phenol and hydroquinone, the latter being oxidized to the highly
      toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell
      lines to hydroquinone has previously been shown to cause various forms of genetic
      damage, including aneusomy and the loss and gain of chromosomes. However, the
      target cells for leukemogenesis are the pluripotent stem cells or early
      progenitor cells which carry the CD34 antigen (CD34(+) cells). In this study,
      human cord blood, which is particularly rich in CD34(+) cells, was exposed to
      hydroquinone for 72 h in a medium that favored CD34(+) cell survival and growth.
      CD34(+) and CD34(-) cells were then isolated. Fluorescence in situ hybridization
      was employed to determine the level of aneusomy of chromosomes 7 and 8 in both
      cell types. CD34(+) cells were generally more susceptible to aneusomy induction
      by hydroquinone than CD34(-) cells. Increased trisomy and monosomy of chromosomes
      7 and 8 were observed in CD34(+) cells (P(trend) < 0.001), whereas in CD34(-)
      cells only an increased level of monosomy 7 was detected (P(trend) = 0.002).
      Particularly striking effects of hydroquinone were observed in CD34(+) cells on
      monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid
      leukemias, suggesting that these aneusomies produced by hydroquinone in CD34(+)
      cells play a role in benzene-induced leukemogenesis.

PMID- 10910949
TI  - Activation of JNK, p38 and ERK mitogen-activated protein kinases by chromium(VI)
      is mediated through oxidative stress but does not affect cytotoxicity.
AB  - In this study we have explored the involvement of oxidative stress in Cr(VI)
      induced JNK, p38 and ERK signaling pathways and their effects on Cr(VI)
      cytotoxicity in human non-small cell lung carcinoma CL3 cells. Exposure to
      K(2)Cr(2)O(7) markedly activated JNK and p38 and moderately activated ERK in a
      dose- (10-80 microM) and time-dependent (1-12 h) manner. The activated p38
      decreased markedly and rapidly and the activated JNK decreased gradually when
      Cr(VI) was removed from the medium. Post-incubation of Cr(VI)-treated cells with
      H(2)O(2) increased the activities of JNK and p38, but not ERK. Co-administering
      Cr(VI) with 3-amino-1,2, 4-triazole (3AT), a catalase inhibitor, enhanced p38
      activation, but did not influence JNK and ERK activation by Cr(VI). Conversely,
      co-administering Cr(VI) with mannitol, a hydroxyl radical scavenger and a Cr(V)
      chelator, reduced p38 activation and increased JNK and ERK activation by Cr(VI).
      These results indicate that p38 activation by Cr(VI) is positively correlated
      with oxidative stress, while JNK activity can be enhanced by either a quencher
      (mannitol) or activator (H(2)O(2)) of redox reactions in Cr(VI)-exposed CL3
      cells. However, both 3AT and mannitol reduced the cytotoxicity of Cr(VI), but
      H(2)O(2) did not. The JNK activated by Cr(VI) was decreased (approximately 50%)
      by expression of a kinase-defective form of MKK7 (MKK7A) but not that of MKK4
      (MKK4KR), suggesting that activation of JNK by Cr(VI) is mediated through MKK7.
      SB202190, a specific inhibitor of p38, markedly decreased JNK but did not change
      ERK activation by Cr(VI). PD98059, a specific inhibitor of ERK kinases MKK1/2,
      blocked ERK and p38 but did not alter JNK activation by Cr(VI). Neither the
      specific kinase inhibitors nor expression of MKK7A altered Cr(VI)-induced
      cytotoxicity. Together, these results suggest that activation of the JNK, p38 and
      ERK pathways by Cr(VI) is mediated through diverse redox mechanisms, yet their
      activation does not correlate with Cr(VI) cytotoxicity.

PMID- 10910950
TI  - Cooperation of bcl-2 and myc in the neoplastic transformation of normal rat liver
      epithelial cells is related to the down-regulation of gap junction-mediated
      intercellular communication.
AB  - The objectives of this study were to isolate several rat liver epithelial cell
      clones containing the human bcl-2 and myc/bcl-2 genes in order to study their
      potential cooperative effect on neoplastic transformation and gap junction
      mediated intercellular communication (GJIC) and to test the hypothesis that the
      loss of GJIC leads to tumorigenesis. Using anchorage-independent growth as a
      surrogate marker for neoplastic transformation, we transfected both normal rat
      liver epithelial cells, WB-F344, and a WB-F344 cell line overexpressing v-myc
      with human bcl-2 cDNA. Those cell lines that only expressed v-myc or human bcl-2
      were unable to form colonies in soft agar. However, those cell lines that
      overexpressed both v-myc and human bcl-2 showed varying ability to form colonies
      in soft agar, which did not correlate with their human bcl-2 expression level. In
      order to test if there was a correlation between cell line growth in soft agar
      and the ability to communicate through gap junctions, we performed scrape load
      dye transfer and fluorescence recovery after photobleaching assays. Our results
      show that v-myc and human bcl-2 can cooperate in the transformation of normal
      cells, but the degree to which the cells are transformed is dependent on the
      cells' ability to communicate through gap junctions.

PMID- 10910951
TI  - Identification of a novel splicing product of the RON receptor tyrosine kinase in
      human colorectal carcinoma cells.
AB  - The RON receptor tyrosine kinase is a 180 kDa heterodimeric protein composed of a
      40 kDa alpha chain and a 145 kDa beta chain with intrinsic tyrosine kinase
      activity. Activation of RON causes cell dissociation, motility and invasion of
      extracellular matrices, suggesting that RON might be involved in tumor
      metastasis. We report here the cloning of a novel splice variant of RON in human
      colorectal carcinoma cell line HT-29. This RON variant is first produced as a
      single chain precursor with a molecular mass of 160 kDa. Proteolytic cleavage
      results in a 40 kDa alpha chain and a short form of the beta chain with a
      molecular mass of 125 kDa. The altered receptor is synthesized from a transcript
      differing from the full-length RON mRNA by an in-frame deletion of 109 amino
      acids in the extracellular domain of the RON beta chain. The consequence of the
      deletion is constitutive activation of the protein with autophosphorylation.
      Expression of the RON variant in colon epithelial CoTr cells results in increased
      cell migration and invasion of extracellular matrices. These data suggest that
      generation of the activated splice variant of RON may contribute to the invasive
      phenotype of human colorectal carcinomas in vivo.

PMID- 10910952
TI  - Morphodensitometric analysis of protein kinase C beta(II) expression in rat
      colon: modulation by diet and relation to in situ cell proliferation and
      apoptosis.
AB  - We have recently demonstrated that overexpression of PKC beta(II) renders
      transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation
      and aberrant crypt foci formation. In order to further investigate the ability of
      PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization
      of PKC beta(II) with respect to cell proliferation and apoptosis along the entire
      colonic crypt axis following carcinogen and diet manipulation. Rats were provided
      diets containing either corn oil [containing n-6 polyunsaturated fatty acids
      (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or
      pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After
      16 weeks, an intermediate time point when no macroscopic tumors are detected,
      colonic sections were utilized for immunohistochemical image analysis and
      immunoblotting. Cell proliferation was measured by incorporation of
      bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase
      mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II)
      staining was localized to the upper portion of the crypt. In comparison, proximal
      crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05)
      PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle
      and lower tertiles). There was also an interaction (P < 0.05) between dietary fat
      and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin >
      corn/cellulose) in all regions of the distal colonic crypt. With respect to
      colonic cell kinetics, proliferation paralleled the increase in PKC beta(II)
      expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal
      surface was inversely proportional to PKC beta(II) expression in the upper
      tertile. These results suggest that an elevation in PKC beta(II) expression along
      the crypt axis in the distal colon is linked to enhancement of cell proliferation
      and suppression of apoptosis, predictive intermediate biomarkers of tumor
      development. Therefore, select dietary factors may confer protection against
      colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II)
      expression.

PMID- 10910953
TI  - Induction of microsatellite mutations by oxidative agents in human lung cancer
      cell lines.
AB  - Genomic instability has been associated with cancer development. Oxidative DNA
      damage seems to contribute to genetic instability observed in cancer. We have
      used human lung cancer cell lines carrying a plasmid vector containing a (CA)(13)
      microsatellite sequence to study frameshift mutations mediated by ROS-generating
      chemicals paraquat and hydrogen peroxide. Exposure of the cells to both paraquat
      and hydrogen peroxide resulted in significantly higher mutation frequencies
      compared with untreated control cells. Mutation frequencies up to 27-fold higher
      than the spontaneous mutation frequencies were obtained. The majority of the
      reversion mutants contained frameshift mutations within the target sequence.
      However, the pattern of deletions and additions was significantly different in
      the two cell lines. These results indicate that oxidative damage may play a role
      in instability of microsatellite sequences in vivo.

PMID- 10910954
TI  - Reduced expression levels of nucleotide excision repair genes in lung cancer: a
      case-control analysis.
AB  - Epidemiological studies have indicated that reduced DNA repair capacity and
      increased DNA adduct levels are associated with increased risk of lung cancer.
      Nucleotide excision repair (NER) is the major pathway in humans for repairing DNA
      adducts induced by smoking-related carcinogens, such as benzo[a]pyrene diol
      epoxide. We hypothesized that genetically determined baseline expression level of
      genes involved in NER is associated with risk of lung cancer. In a pilot case
      control study, we measured the relative expression levels of five NER genes
      [ERCC1, XPB/ERCC3, XPG/ERCC5, CSB/ERCC6 and XPC (ERCC, excision repair cross
      complementing; CSB, Cockayne's syndrome complementary group B)] in
      phytohemagglutinin-stimulated peripheral lymphocytes obtained from 75 lung cancer
      patients and 95 controls using a newly developed multiplex RT-PCR assay. Cases
      and controls were matched on age, sex, ethnicity and tobacco use. The expression
      level of the beta-actin gene was used as an internal control for the relative
      quantitation. We observed a 12.2 and 12.5% decrease in the baseline expression
      levels of XPG/ERCC5 and CSB/ERCC6, respectively, in cases compared with controls.
      These differences were statistically significant (P < 0.01) when the median
      expression level in the controls was used as the cut-off point, the lung cancer
      patients were significantly more likely than the controls to have reduced
      expression levels of XPG/ERCC5 [odds ratio (OR), 2.32; 95% confidence interval
      (CI), 1.22-4.43] and CSB/ERCC6 (OR, 2.49; 95% CI, 1.28-4.84). There was also a
      dose-response relationship between reduced expression levels and increased lung
      cancer risk (trend test: P < 0.01). Our results suggest that individuals whose
      expression levels of XPG/ERCC5 and CSB/ERCC6 are reduced may be at higher risk of
      lung cancer.

PMID- 10910955
TI  - Effects of vitamin E and selenium supplementation on esophageal
      adenocarcinogenesis in a surgical model with rats.
AB  - Two well-known antioxidative nutrients, vitamin E and selenium, were used in this
      study to investigate possible inhibitory action against the formation of
      esophageal adenocarcinoma (EAC) in rats. In this model, carcinogenesis is
      believed to be driven by oxidative stress. Male Sprague-Dawley rats (8 weeks old)
      were divided into four groups and received esophagoduodenal anastomosis (EDA)
      surgery plus iron supplementation (12 mg/kg/week). Vitamin E and selenium were
      supplemented in the diet in the forms of alpha-tocopheryl acetate (750 IU/kg) and
      sodium selenate (1.7 mg Se/kg), which were 10 times the regular amounts in the
      basic AIN93M diet. At 40 weeks after surgery, all the EDA groups had lower body
      weights than the non-operated control group. Iron nutrition (hemoglobin, total
      serum iron and transferrin saturation) was normal as a result of iron
      supplementation after EDA. Vitamin E supplementation maintained the normal plasma
      level of alpha-tocopherol in EDA rats, but not those of gamma-tocopherol and
      retinol. Selenium supplementation increased the serum and liver selenium contents
      of the EDA rats. Histopathological analysis showed that selenium supplementation
      increased the incidence of EAC and the tumor volume. The selenium level in the
      tumor is higher than that in the duodenum of the same animal. Vitamin E
      supplementation, however, inhibited carcinogenesis, especially in the selenium
      supplemented group. We believe that vitamin E exerts its effect through its
      antioxidative properties, and a high dose of inorganic selenium may promote
      carcinogenesis by enhancing oxidative stress.

PMID- 10910956
TI  - A potential mechanism for fumonisin B(1)-mediated hepatocarcinogenesis: cyclin D1
      stabilization associated with activation of Akt and inhibition of GSK-3beta
      activity.
AB  - Fumonisin B(1) (FB(1)) is a worldwide corn contaminant and has been
      epidemiologically linked to the high incidence of human esophageal cancer in
      South Africa and China. FB(1) is hepatocarcinogenic in rats by an unknown
      mechanism. Inhibition of ceramide synthase and disruption of membrane
      phospholipids have been shown to be mechanisms of toxicity. Here we show
      overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver
      specimens obtained from a long-term feeding study of FB(1) in rats. In rats fed
      FB(1) short-term, cyclin D1 protein levels in liver were increased up to five
      fold in a dose-responsive manner. Northern blot analysis demonstrated no increase
      in mRNA levels of cyclin D1. 2D electrophoresis of cyclin D1 protein in FB(1)
      treated samples showed a distinct pattern of migration (presence of less
      negatively charged form of the protein) that differed from controls. Recently, it
      has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase
      3beta (GSK-3beta) on a single threonine residue (Thr-286) positively regulates
      proteosomal degradation of cyclin D1. In FB(1)-treated samples we detected GSK
      3beta phosphorylated on serine 9; activated protein kinase B (Akt) appears to be
      responsible for this activity-inhibiting phosphorylation. These findings suggest
      that overexpression of cyclin D1 results from stabilization due to a lack of
      phosphorylation mediated by GSK-3beta. We also observed an increase in cyclin
      dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB(1)-treated samples;
      additionally, elevated Cdk4 activity was shown by increased phosphorylation of
      the retinoblastoma protein. In summary, the activation of Akt leads to increased
      survival, inhibition of GSK-3beta activity and post-translational stabilization
      of cyclin D1, all events responsible for disruption of the cell cycle G(1)/S
      restriction point in hepatocytes. This is the first report suggesting the
      mechanism by which FB(1) acts as a carcinogen.

PMID- 10910957
TI  - Phytic acid in wheat bran affects colon morphology, cell differentiation and
      apoptosis.
AB  - Wheat bran (WB) and its component phytic acid (PA) have both been shown to
      decrease early biomarkers of colon carcinogenesis, i.e. the PCNA labeling index
      of cell proliferation and certain aberrant crypt foci parameters. However, it is
      not known how WB and PA alter other biomarkers of colon cancer risk, such as rate
      of apoptosis and degree of differentiation, or how they affect colon morphology.
      Thus, the objectives of this study were to determine the effects of WB on these
      parameters, to see if PA contributes to these effects and whether there is a
      difference between endogenous and exogenously added PA. Five groups of
      azoxymethane-treated male Fischer 344 rats were fed a basal control diet (BD) or
      BD supplemented with either 25% wheat bran, 25% dephytinized wheat bran (DWB),
      25% DWB plus 1.0% PA or 1.0% PA for 100 days. The WB, DWB and PA diets
      significantly increased the rate of apoptosis and cell differentiation in the
      whole crypt and the top 40% of the crypt. The WB, DWB and PA diets also
      significantly increased cell apoptosis in the bottom 60% of the crypt, while all
      the treatment groups significantly increased cell differentiation versus the BD
      group in the bottom 60% of the crypt. In addition, the WB, DWB and PA diets
      decreased the number of crypts per millimeter of colon, while the DWB and PA
      diets also decreased crypt height measured as number of cells. It is concluded
      that WB, partly due to its dietary fiber and endogenous PA, and exogenous PA when
      added to a low fiber diet can increase cell apoptosis and differentiation and
      favorably affect colon morphology.

PMID- 10910958
TI  - Promotion by sodium barbital induces early development but does not increase the
      multiplicity of hereditary renal tumors in Eker rats.
AB  - Induced cell proliferation is important in the mode of action of many non
      genotoxic renal carcinogens. Since Tsc2 mutant (Eker) rats are genetically
      predisposed to the development of renal cell tumors, they provide a useful animal
      model in which to study the action of renal carcinogens. Sodium barbital was used
      as a model non-genotoxic renal carcinogen to test whether a concentration that
      increased renal tubular proliferation without severe nephrotoxicity would enhance
      tumor induction in a hereditary tumor model. First, a subchronic concentration
      response study was conducted in wild-type male Long-Evans rats to determine
      increased cell proliferation without severe nephrotoxicity. Rats were dosed with
      sodium barbital in the feed at 0, 50, 250, 500, 1000, 2000 or 4000 p.p.m. for 3
      or 8 weeks. Cell proliferation within the cortex and nephrotoxicity were
      quantitated. Enhanced proliferation with minimal nephrotoxicity occurred at 500
      p.p.m. A second study was conducted in male Tsc2 mutant rats given sodium
      barbital in the feed at 0, 100 or 500 p.p.m. from 9 weeks of age to either 6 or
      12 months of age. An additional group of rats was treated with sodium barbital
      for 6 months and then provided control feed until 12 months of age. Rats
      necropsied at 6 months of age had a concentration-dependent increase in
      preneoplastic and total renal lesions. Sodium barbital-treated rats necropsied at
      12 months of age had numbers of lesions that were not different from controls.
      Total combined preneoplastic and neoplastic lesions in the 6 month, high dose
      group was the same as the 12 month control group. These data show that sodium
      barbital caused progression to the stage of spontaneous renal lesions in Tsc2
      mutant rats but did not increase their overall number. These data suggest that
      enhanced cell proliferation without significant cytotoxicity exerted a
      promotional influence in this hereditary model.

PMID- 10910960
TI  - Sequential and morphological analyses of aberrant crypt foci formation in mice of
      differing susceptibility to azoxymethane-induced colon carcinogenesis.
AB  - Aberrant crypt foci (ACF), putative preneoplastic lesions, are early
      morphological changes induced by the colon carcinogen azoxymethane (AOM).
      Although inbred mice differ markedly in their susceptibility to AOM
      carcinogenesis, we have previously shown that ACF develop in both resistant and
      sensitive mouse strains after AOM treatment. The purpose of this study was to
      examine the sequential development and identify the morphological characteristics
      of ACF induced by AOM in the distal colon of sensitive and resistant mice. A/J
      (highly susceptible), SWR/J (relatively susceptible) and AKR/J (resistant) mice
      were treated with 10 mg/kg AOM or saline i.p. once a week for 6 weeks and were
      killed at 1, 2, 4, 6, 9 and 24 weeks after the last injection. The distal colons
      were stained with methylene blue and the numbers of ACF and tumors determined.
      Tumors were present as early as 4 weeks after AOM exposure in SWR/J and A/J mice
      and increased in frequency throughout the study in both strains. No tumors
      developed in the AKR/J mice. ACF, however, formed in all strains of mice. The
      greatest difference between susceptible and resistant strains was in the number
      of large ACF that developed at later time points. Furthermore, morphometric
      analysis revealed that A/J mice had the highest percentage of dysplastic ACF,
      followed by SWR/J mice. These data indicate that the difference in cancer risk
      from AOM may be due to the lack of progression of smaller ACF in the resistant
      mice and to the development of dysplasia in a higher percentage of ACF from
      susceptible strains.

PMID- 10910959
TI  - Identification of the human liver microsomal cytochrome P450s involved in the
      metabolism of N-nitrosodi-n-propylamine.
AB  - The ability of human liver cytochrome P450s to metabolize the environmental
      carcinogen N-nitrosodi-n-propylamine (NDPA) was investigated. The maximum rate of
      NDPA depropylation in seven human liver microsomal samples was 1.15 nmol/min/mg
      (range 0.53-2.60). Troleandomycin, a P450 3A4/5 inhibitor, inhibited
      depropylation modestly (10-60%) in three of seven samples. Diethyldithiocarbamic
      acid, a potent 2E1 inhibitor, and a 2E1 inhibitory monoclonal antibody (mAb)
      inhibited the reaction in all samples (23 to almost 100%). No significant
      inhibition was observed with the 2C9 inhibitor sulfaphenazole or with mAbs to
      3A4, 2A6 and 2D6. The 2C8/9/18/19 mAb inhibited depropylation in one sample by
      approximately 25% and approximately 25% of the activity in another sample could
      not be accounted for by the inhibitors. Denitrosation of NDPA by three of the
      microsomal samples exhibited low K(m) values (51-86 microM) while two of these
      also had high K(m) values (2.6 and 4.6 mM). Purified human P450 2B6 and 3A4 and
      human P450 2A6, 2C8, 2C9 and 2D6 membranes had high K(m) values relative to their
      maximum turnover rates and are unlikely to participate in NDPA metabolism at
      micromolar concentrations. Conversely, purified rabbit 2E1 exhibited K(m) and
      V(max) values for depropylation of 52 microM and 13.4 nmol
      propionaldehyde/min/nmol P450, respectively. Values for denitrosation were 66
      microM and 1.44 nmol nitrite/min/nmol P450, respectively. The toxicity of NDPA in
      transfected human liver epithelial cells expressing 2E1 was dose dependent down
      to 50 microM. No toxicity was observed in control cells or those expressing 2A6.
      These results indicate that 2E1 is the major human liver microsomal isoform
      responsible for NDPA metabolism at low micromolar concentrations. We also show
      that purified P450s catalyze the denitrosation of NDPA at approximately 10-20% of
      the rate of depropylation and K(m) values for both reactions are the same for
      each isozyme. This is consistent with the formation of an initial intermediate
      common to both pathways, presumably an alpha-nitrosamino radical.

PMID- 10910961
TI  - Loss of DNA-protein crosslinks from formaldehyde-exposed cells occurs through
      spontaneous hydrolysis and an active repair process linked to proteosome
      function.
AB  - DNA-protein crosslinks (DPC) involving all major histones are the dominant form
      of DNA damage in formaldehyde-exposed cells. In order to understand the repair
      mechanisms for these lesions we conducted detailed analysis of the stability of
      formaldehyde-induced DPC in vitro and in human cells. DNA-histone linkages were
      found to be hydrolytically unstable, with t(1/2) = 18.3 h at 37 degrees C. When
      histones were allowed to remain bound to DNA after crosslink breakage, the half
      life of DPC increased to 26.3 h. This suggests that approximately 30% of
      spontaneously broken DPC could be re-established under physiological conditions.
      The half-lives of DPC in three human cell lines (HF/SV fibroblasts, kidney Ad293
      and lung A549 cells) were similar and averaged 12.5 h (range 11.6-13.0 h). After
      adjustment for spontaneous loss, an active repair process was calculated to
      eliminate DPC from these cells with an average t(1/2) = 23.3 h. Removal of DPC
      from peripheral human lymphocytes was slower (t(1/2) = 18.1 h), due to
      inefficient active repair (t(1/2) = 66.6 h). This indicates that the major
      portion of DPC is lost from lymphocytes through spontaneous hydrolysis rather
      than being actively repaired. Depletion of intracellular glutathione from A549
      cells had no significant effect on the initial levels of DPC, the rate of their
      repair or cell survival. Nucleotide excision repair does not appear to be
      involved in the removal of DPC, since the kinetics of DPC elimination in XP-A and
      XP-F fibroblasts were very similar to normal cells. Incubation of normal or XP-A
      cells with lactacystin, a specific inhibitor of proteosomes, caused inhibition of
      DPC repair, suggesting that the active removal of DPC in cells may involve
      proteolytic degradation of crosslinked proteins. XP-F cells showed somewhat
      higher sensitivity to formaldehyde, possibly signaling participation of XPF
      protein in the removal of residual peptide-DNA adducts.

PMID- 10910962
TI  - Multicolour FISH detection of radioactive iodine-induced 17cen-p53 chromosomal
      breakage in buccal cells from therapeutically exposed patients.
AB  - Simultaneous labelling of 17cen and the p53 locus by multicolour FISH was used to
      monitor radioactive iodine-induced structural and numerical chromosome
      abnormalities in buccal cells from 29 hyperthyroidism and thyroid cancer patients
      sampled before and after therapeutic treatment. This novel methodology allowed
      the efficient detection of 17p deletions leading to p53 allelic deletions, 17p
      gains and whole chromosome 17 numerical abnormalities in epithelial cells. Highly
      significant increases in the frequency of cells with (i) 17p abnormalities (1.8
      fold; P < 0.001), including p53 monoallelic deletions (2.1-fold; P < 0.001) and
      17p gains (3.5-fold; P < 0.001); (ii) chromosome 17 numerical abnormalities (2
      fold; P < 0.001); and (iii) simultaneous 17p breakage and chromosome 17 numerical
      abnormalities (2.3-fold; P < 0.001), were observed after radioactive iodine
      treatment. As expected, the major contribution to these increases was detected in
      hyperthyroidism patients compared with thyroid cancer patients who suffered
      thyroidectomy before radioactive iodine exposure and, therefore, experienced a
      rapid elimination of the radioisotope. Considering that both the genetic
      endpoints and the target tissue are extremely relevant in carcinogenesis, it is
      suggested that the observed genetic damage could contribute to the reported
      increase in cancer risk of people therapeutically or accidentally exposed to
      radioactive iodine.

PMID- 10910963
TI  - Duodenal-content reflux esophagitis induces the development of glandular
      metaplasia and adenosquamous carcinoma in rats.
AB  - Recent studies have demonstrated that refluxed duodenal contents cause esophageal
      carcinoma in rats without exposure to carcinogens. The histopathological spectrum
      of these carcinomas includes squamous-cell carcinoma, adenocarcinoma and
      adenosquamous carcinoma. Pure adenocarcinomas are thought to arise in areas of
      columnar metaplasia adjacent to the anastomosis, similar to Barrett's esophagus
      in humans. In contrast, the histogenesis of adenosquamous carcinomas is unclear.
      The purpose here was to investigate the pathogenesis of esophageal adenosquamous
      carcinomas in a time-course experiment of chronic duodenal-content reflux without
      carcinogen. Forty-two 8-week-old male Sprague-Dawley rats were divided into seven
      groups and exposed to duodenal-content esophageal reflux during 10, 15, 20, 25,
      30, 35 and 40 weeks, respectively. All animals underwent an esophagojejunostomy
      with gastric preservation in order to produce chronic esophagitis. The rats
      received a standard diet without addition of carcinogens. An increasing incidence
      of glandular metaplasia and carcinoma was observed over the time course, starting
      at 20 weeks. After 40 weeks of reflux, multiple foci of glandular metaplasia and
      adenosquamous carcinoma were found in 83 and 50% of the animals, respectively.
      Most of the carcinomas occurred in the middle and proximal esophagus and had a
      dual pattern of differentiation, glandular and squamous. These findings confirm
      that duodenal content reflux alone has a carcinogenic effect. We propose that
      chronic duodenal reflux induces the development of metaplastic cells with
      glandular differentiation from the stem cells of squamous epithelium, and that
      glandular metaplastic foci are the morphological element from which tumors with a
      dual pattern of differentiation arise.

PMID- 10910964
TI  - Effect of chlorinated hydrocarbons on expression of cytochrome P450 1A1, 1A2 and
      1B1 and 2- and 4-hydroxylation of 17beta-estradiol in female Sprague-Dawley rats.
AB  - Chlorinated hydrocarbons (CHCs) are environmental contaminants that bioaccumulate
      and hence are detected in human tissues. Epidemiological evidence suggests that
      the increased incidence of a variety of human cancers, such as lymphoma, leukemia
      and liver and breast cancers, might be attributed to exposure to these agents.
      The ability of CHCs to disrupt estrogen homeostasis is hypothesized to be
      responsible for their biological effects. The present study examined the effect
      of CHCs on the expression of cytochrome P450 (CYP)1A1, CYP1A2 and CYP1B1 mRNAs
      and the consequent 2- and 4-hydroxylation of 17beta-estradiol (E(2)) in female
      Sprague-Dawley rats. Animals were administered a single dose of the LD(50) of
      2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) (25 microg/kg), 2, 4
      dichlorophenoxyacetic acid (2,4-D) (375 mg/kg) and dieldrin (DED) (38 mg/kg) by
      gavage. Seventy-two hours after treatment, increased expression of CYP1A1, CYP1A2
      and CYP1B1 was observed in the liver, kidney and mammary tissue. Since CYP1A and
      CYP1B1 are the major enzymes catalyzing 2- and 4-hydroxylation of E(2),
      respectively, the effect of these CHCs on the metabolism of E(2) was investigated
      in rat tissues. Formation of 2- and 4-catechol estrogens was increased in a
      tissue-specific manner in response to treatment. TCDD was the most potent inducer
      for CYP1 enzyme mRNA and for the 2- and 4-hydroxylation of E(2). 2,4-D and DED
      induced similar responses, but less than that of TCDD. These results suggest that
      induction of CYP1 family enzymes and consequent increases in estrogen metabolism
      by CHCs in target tissues may be factors contributing to the biological effects
      associated with exposure to these agents.

PMID- 10910965
TI  - 7H-benzo[c]fluorene: a major DNA adduct-forming component of coal tar.
AB  - Coal tar is a complex mixture that exhibits high carcinogenic potency in lungs of
      animals when administered in the diet. Studies have noted that lung tumor
      induction does not correlate with the benzo[a]pyrene content of coal tar,
      suggesting that other hydrocarbons may be involved in the observed
      tumorigenicity. Our previous studies have demonstrated that a major 'unknown'
      chemical-DNA adduct is formed in the lung of mice exposed to coal tar. We have
      used an in vitro rat microsomal activation system to generate the 'unknown'
      adduct with neat coal tar and fractions of coal tar obtained by chemical
      fractionation and HPLC. Chemical-DNA adduct formation was evaluated by (32)P
      postlabeling using both multi-dimensional TLC and HPLC. GC-MS analysis of the
      coal tar fractions obtained from HPLC, which produced the 'unknown' adduct in
      vitro, demonstrated that the adducting hydrocarbon had a mass of 216. A careful
      evaluation of candidate hydrocarbons led to the conclusion that a benzofluorene
      derivative may be responsible for forming the 'unknown' chemical-DNA adduct.
      Comparative in vitro and in vivo studies on the adducting properties of all three
      isomers of benzofluorene indicated that 7H-benzo[c]fluorene is responsible for
      producing the 'unknown' adduct observed in the lung of mice ingesting coal tar.
      Animal feeding studies also demonstrated that 7H-benzo[c]fluorene formed
      considerably more lung DNA adducts than 11H-benzo[a]fluorene and 11H
      benzo[b]fluorene. These data indicate that the four-ring polycyclic aromatic
      hydrocarbon 7H-benzo[c]fluorene, a hydrocarbon not previously shown to form DNA
      adducts in lung, is in fact a potent lung DNA adductor and is a candidate PAH for
      causing lung tumors in animals treated with coal tar.

PMID- 10910966
TI  - Diverse chemical carcinogens fail to induce G(1) arrest in MCF-7 cells.
AB  - The effect of three reactive potent chemical carcinogens on the passage of MCF-7
      cells through the cell cycle was investigated. While these cells, which express
      wild-type p53, were arrested in G(1) after treatment with actinomycin D (a
      positive control), treatment with anti-benzo[a]pyrene dihydrodiol epoxide, N
      acetoxy-N-2-fluorenylacetamide or N-methyl-N'-nitro-N-nitrosoguanidine, at doses
      consistent with survival of significant numbers of cells, caused the cells to
      accumulate in S phase, with little increase in those in G(1). This property of
      these three reactive potent carcinogens, of diverse chemical types, to induce
      evasion of G(1) arrest (the stealth property) presumably increases the likelihood
      of malignant change, because DNA replication continues on a damaged template.
      This stealth characteristic may be a major contributor to the tumorigenicity of
      DNA-adducting chemical carcinogens in general.

PMID- 10910967
TI  - Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting
      bax and p21(CIP) expression.
AB  - We investigated whether resveratrol (RV) affects azoxymethane (AOM)-induced colon
      carcinogenesis, by administering RV (200 microg/kg/day in drinking water) to male
      F344 rats for 100 days, beginning 10 days before carcinogen treatment (two weekly
      doses of 15 mg/kg AOM). Aberrant crypt foci (ACF) were isolated and
      proliferation, apoptosis and expression of the cell cycle genes bax and p21 were
      determined. RV significantly reduced the number of ACF/colon [25.7 +/- 3.6 (mean
      +/- SEM) versus 39.4 +/- 3.3 in controls; P < 0.01] and their multiplicity (2.7
      +/- 0.3 versus 4.9 +/- 0.6 in controls; P < 0.01), and also abolished large ACF.
      In RV-treated rats, bax expression was enhanced in ACF but not in the surrounding
      mucosa. In both controls and RV-treated rats, proliferation was higher in ACF
      than in normal mucosa. p21 was expressed in ACF of controls and of RV-treated
      rats and in normal mucosa of controls, but was lost in normal mucosa of RV
      treated animals. In conclusion, the results suggest a protective role of RV in
      colon carcinogenesis with a mechanism involving changes in bax and p21
      expression.

PMID- 10910968
TI  - Genomic instability-based transgenic models of prostate cancer.
AB  - To develop animal models that represent the broad spectrum of human prostate
      cancer, we created transgenic mice with targeted prostate-specific expression of
      two genes (ECO:RI and c-fos) implicated in the induction of genomic instability.
      Expression of the transgenes was restricted to prostate epithelial cells by
      coupling them to the tissue-specific, hormonally regulated probasin promoter
      (PB). The effects of transgene expression were examined histologically in
      prostate sections at time points taken from 4 to 24 months of age. The
      progressive presence of regions of mild-to-severe hyperplasia, low- and high
      grade prostatic intra-epithelial neoplasia, and well-differentiated
      adenocarcinoma was observed in both PBECO:RI lines but no significant pathology
      was detected in the PBfos line. Prostate tissue of PBECO:RI mice was examined for
      expression of p53, proliferating cell nuclear antigen (PCNA) and Ki67 at multiple
      time points. Although p53 does not appear to be mutated, levels of PCNA and Ki67
      are elevated and correlate with the severity of the prostatic lesions. Overall,
      pre-neoplastic and neoplastic stages represented in the PBECO:RI model showed
      similarity to corresponding early stages of the human disease. This genomic
      instability-based model will be used to study the mechanisms involved in the
      early stages of prostate carcinogenesis and to investigate the nature of
      subsequent events necessary for the progression to advanced disease.

PMID- 10910969
TI  - Transport of free and N-linked oligomannoside species across the rough
      endoplasmic reticulum membranes.
AB  - The N-glycosylation process occurs in the rough endoplasmic reticulum. It
      requires the transport of glycosyl donors into the lumen and the exit of the
      glycosylated products toward the secretory pathway. Besides this main flow, the
      formation of free oligomannosides, glycopeptides, and misfolded glycoproteins
      which do not enter the secretory pathway and are cleared out of the endoplasmic
      reticulum by specific transports has been demonstrated. This review focuses on
      the export mechanisms of these three side products of the N-glycosylation process
      and discusses their physiological significance.

PMID- 10910970
TI  - Influenza virus infection of desialylated cells.
AB  - Sialic acid has long been considered to be the sole receptor for influenza virus.
      The viral hemagglutinin (HA) is known to bind cell surface sialic acid, and
      sialic acids on viral glyco-proteins are cleaved by the viral neuraminidase (NA)
      to promote efficient release of progeny virus particles. However, NWS-Mvi, a
      mutant virus completely lacking NA, grows well in MDCK cells continuously treated
      with exogenous neuraminidase (sialidase). Exogenous sialidase quantitatively
      releases all sialic acids from purified glycoproteins and glycolipids of MDCK
      cells and efficiently removes surface sialic acid from intact cells. Binding of
      NWS-Mvi and parent influenza viruses to MDCK cells is indistinguishable, and is
      only partially reduced by sialidase treatment of the cells. Both mutant and wild
      type viruses enter enzymatically desialylated cells and initiate transcription.
      The ability of influenza A reassortant viruses to infect desialylated cells is
      shared by recent H3N2 clinical isolates, suggesting that this may be a general
      property of influenza A viruses. We propose that influenza virus infection can
      result from sialic acid-independent receptors, either directly or in a multistage
      process. When sialic acid is present, it may act to enhance virus binding to the
      cell surface to increase interaction with secondary receptors to mediate entry.
      Understanding virus entry will be critical to further efforts in infection
      control and prevention.

PMID- 10910971
TI  - Characterization of the rabbit homolog of human MUC1 glycoprotein isolated from
      bladder by affinity chromatography on immobilized jacalin.
AB  - The urinary bladder is lined by transitional epithelium, the glycocalyx on the
      luminal surface has interesting properties and is implicated in protective
      functions. Glycoconjugates are major components of the glycocalyx, but their
      biochemical nature is not well understood. Previous studies on rabbit bladder
      indicated the presence of significant levels of sialoglycoproteins compared to
      glycosaminoglycans in the epithelium. In this study, rabbit explant cultures were
      radiolabeled by precursor sugars or amino acids and a major lectin-reactive
      glycoprotein of rabbit bladder mucosa was isolated by affinity chromatography on
      jacalin-agarose. The radiolabeled glycoprotein was purified to homogeneity by a
      second cycle on the lectin column, followed by gel filtration and density
      gradient centrifugation. The average molecular mass of the glycoprotein was
      estimated to be 245 kDa and 210 kDa by gel filtration and SDS-PAGE, respectively.
      Its buoyant density was 1.40 g/ml, suggesting a carbohydrate content of
      approximately 50%. The percent distribution of glucosamine-derived tritium label
      in sialic acid, galactosamine, and glucosamine was 30, 52, and 18, respectively.
      The glycoprotein consisted entirely of small sialylated and neutral
      oligosaccharides O-glycosidically linked to serine and threonine residues. The
      same glycoprotein could be immunoprecipitated with an antibody against the
      carboxy terminal 17 amino acid peptide of human MUC1 mucin glycoprotein. This
      suggests that this mucin glycoprotein is the rabbit homolog of MUC1 glycoprotein,
      which has been previously established to be a component of human bladder
      urothelium and has been purified from human urine and biochemically
      characterized.

PMID- 10910972
TI  - Exploring the glycan repertoire of genetically modified mice by isolation and
      profiling of the major glycan classes and nano-NMR analysis of glycan mixtures.
AB  - The production of mice with genetic alterations in glycosyltransferases has
      highlighted the need to isolate and study complex mixtures of the major classes
      of oligosaccharides (glycans) from intact tissues. We have found that nano-NMR
      spectroscopy of whole mixtures of N- and O-glycans can complement HPLC profiling
      methods for elucidating structural details. Working toward obtaining such glycan
      mixtures from mouse tissues, we decided to develop an approach to isolate not
      only N- and O-glycans, but also to separate out glycosphingolipids,
      glycosaminoglycans and glycosylphosphatidylinositol anchors. We describe here a
      comprehensive Glycan Isolation Protocol that is based primarily upon the
      physicochemical characteristics of the molecules, and requires only commonly
      available reagents and equipment. Using radiolabeled internal tracers, we show
      that recovery of each major class of glycans is as good or better than with
      conventional approaches for isolating individual classes, and that cross
      contamination is minimal. The recovered glycans are of sufficient purity to
      provide a "glycoprofile" of a cell type or tissue. We applied this approach to
      compare the N- and O-glycans from wild type mouse tissues with those from mice
      genetically deficient in glycosyltransferases. N- and O-glycan mixtures from
      organs of mice deficient in ST6Gal-I (CMP-Sia:Galbeta1-4GlcNAc alpha2-6
      sialyltransferase) were studied by the nano-NMR spectroscopy approach, showing no
      detectable alpha2-6-linked sialic acids. Thus, ST6Gal-I is likely responsible for
      generating most or all of these residues in normal mice. Similar studies indicate
      that this linkage is very rare in ganglioside glycans, even in wild-type tissues.
      In mice deficient in GalNAcT-8 (UDP-GalNAc:polypeptide O-Ser/Thr GalNAc
      transferase 8), HPLC profiling indicates that O-glycans persist in the thymus in
      large amounts, without a major change in overall profile, suggesting that other
      enzymes can synthesize the GalNAc-O-Ser/Thr linkage in this tissue. These results
      demonstrate the applicability of nano-NMR spectroscopy to complex glycan
      mixtures, as well as the versatility of the Glycan Isolation Protocol, which
      makes possible the concurrent examination of multiple glycan classes from intact
      vertebrate tissues.

PMID- 10910973
TI  - Exploring the outcome of genetic modifications of glycosylation in cultured cell
      lines by concurrent isolation of the major classes of vertebrate glycans.
AB  - In the preceding article (Manzi,A.E., Norgard-Sumnicht,K., Argade,S., Marth,J.D.,
      van Halbeek,H. and Varki.A. [2000] GLYCOBIOLOGY:, 10, 669-688), we reported a
      comprehensive approach for the extraction, fractionation, and isolation of all of
      the major classes of sugar chains (glycans) from vertebrate tissues. Here we
      apply this "Glycan Isolation Protocol" to a variety of cultured mammalian cell
      lines, including two wild-type Chinese hamster ovary (CHO) cell lines and some of
      their genetically modified variants that were predicted or known to have defined
      abnormalities in the biosynthesis of one or more classes of glycans. We also use
      this approach to characterize clone 489, a new derivative of the GAG-deficient
      CHO clone pgsA-745, in which sulfation has been restored by transfection of a
      wild-type CHO cDNA library. By metabolically labeling the cell lines with [6
      (3)H]glucosamine we were able to monitor the recovery of all major classes of
      glycans. The results allow us to reach several conclusions: first, the protocol
      described in the preceding paper is further validated by finding good recovery of
      total radioactivity and appropriate distribution of label in the correct glycan
      classes in the fractions from a variety of cell lines; second, the amount of
      radioactivity recovered in free glycosylphosphatidylinositol (GPI) lipids is
      remarkably high when compared to that found in GPI anchors, with the former being
      the dominant form in some cells; third, cells with known genetic mutations in
      specific glycosylation pathways are shown to have the expected changes in the
      distribution of recovered radioactivity in the appropriate fractions; fourth, the
      N- and O- glycans recovered via the protocol are of adequate quality to
      demonstrate marked differences in their structural profiles and/or content;
      fifth, the protocol can pick up unexpected differences of glycan classes not
      predicted to be affected by the primary defect; finally, the reappearance of
      sulfation in the novel clone 489 is not due to restoration of GAG sulfation, but
      rather due to the new expression of sulfation in the fraction enriched in N- and
      O-linked glycopeptides. These results demonstrate the power of this comprehensive
      approach for the concurrent exploration and profiling of the different major
      classes of glycans in cells.

PMID- 10910974
TI  - Expression of histo-blood group antigens by lipopolysaccharides of Helicobacter
      pylori strains from asian hosts: the propensity to express type 1 blood-group
      antigens.
AB  - Past studies have shown that the cell surface lipopolysaccharides (LPSs) of the
      ubiquitous human gastric pathogen Helicobacter pylori (a type 1 carcinogen)
      isolated from people residing in Europe and North America express predominantly
      type 2 Lewis x (Le(x)) and Le(y) epitopes and, infrequently, type 1 Le(a), Le(b),
      and Le(d) antigens. This production of Lewis blood-group structures by H. pylori
      LPSs, similar to those found in the surfaces of human gastric cells, allows the
      bacterium to mimic its human niche. In this study, LPSs of H.pylori strains
      extracted from patients living in China, Japan, and Singapore were chemically and
      serologically analyzed. When compared with Western H.pylori LPSs, these Asian
      strains showed a stronger tendency to produce type 1 blood groups. Of particular
      interest, and novel observations in H.pylori, the O-chain regions of strains F
      58C and R-58A carried type 1 Le(a) without the presence of type 2 Le(x), strains
      R-7A and H607 were shown to have the capability of producing the type 1 blood
      group A antigen, and strains CA2, H507, and H428 expressed simultaneously the
      difucosyl isomeric antigens, type 1 Le(b) and type 2 Le(y). The apparent
      proclivity for the production of type 1 histo-blood group antigens in Asian
      H.pylori LPSs, as compared with Western strains, may be an adaptive evolutionary
      effect in that differences in the gastric cell surfaces of the respective hosts
      might be significantly dissimilar to select for the formation of different LPS
      structures on the resident H.pylori strain.

PMID- 10910975
TI  - The spacing of S-domains on HS glycosaminoglycans determines whether the chain is
      a substrate for intracellular heparanases.
AB  - Heparanases are mammalian endoglucuronidases that degrade heparan sulfate (HS)
      glycosaminoglycans to short 5-6 kDa pieces. In the Golgi, HS glycosaminoglycans
      are modified by a series of interdependent reactions which result in chains that
      have regions rich in N- and O-sulfate groups and iduronate residues (S-domains),
      separated by regions that are nearly devoid of sulfate. Structural analysis of
      the short HS chains produced by Chinese hamster ovary (CHO) cell heparanases
      indicate that the enzymes recognize differences in sulfate content between S
      domains and unmodified sequences, and cleave the chain at junctions between these
      regions. To look more closely at whether the spacing of S-domains on the gly-
      cosaminoglycan influences its ability to be cleaved by heparanases, we examined
      the susceptibility of the HS chains synthesized by the proteoglycan synthesis
      mutant, pgsE-606. PGS:E-606 cells are deficient in the modification enzyme N
      deacetylase/N-sulfotransferase I, and synthesize HS chains that have fewer N- and
      O-sulfate groups and iduronate residues compared to wild-type (Bame et al.,
      (1991), J. Biol. Chem., 266, 10287). HS glycosaminoglycans were isolated from
      wild-type and pgsE-606 cells and separated into populations based on sulfate
      content. Compared to wild-type HS, which has 14 S-domains, pgsE-606 cells
      synthesize three HS species, 606-1, 606-2, and 606-3, with 1, 4, and 8 S-domains,
      respectively. The spacing of the S-domains on the pgsE-606 HS chains is similar
      to the spacing the modified sequences on wild-type HS, indicating that each
      mutant glycosaminoglycan is composed of wild-type-like sequences and sequences
      devoid of S-domains. When incubated with partially purified CHO heparanases, only
      the portion of the mutant HS chains that had S-domains were degraded. Structural
      analysis of the heparanase-products confirmed that both the number and the
      arrangement of S-domains on the HS glycosaminoglycan are important for heparanase
      susceptibility. The structure of the different pgsE-606 HS chains also suggests
      mechanisms for the placement of S-domains when the gly- cosaminoglycan is
      synthesized.

PMID- 10910976
TI  - Effect of proteasome inhibitors on the release into the cytosol of free
      polymannose oligosaccharides from glycoproteins.
AB  - Prompted by previous observations which suggested that the release of polymannose
      oligosaccharides shortly after the cotranslational N-glycosylation of proteins is
      a function of the ER-associated quality control system (Moore and Spiro (1994) J.
      Biol. Chem., 269, 12715-12721), we evaluated the effect which proteasome
      inhibitors have on the appearance of these free saccharide components. Employing
      as a model system castanospermine-treated BW5147 mouse T-lymphoma cells in which
      accelerated degradation of the T-cell receptor (TCR) alpha subunit takes place
      (Kearse et al. (1994) EMBO J., 13, 3678-3686), we noted that both lactacystin and
      N-acetyl-L-leucyl-L-leucyl-L-norleucinal, but not leupeptin, brought about a
      rapid and substantial reduction in the release of free polymannose
      oligosaccharides into the cytosol during pulse-chase studies, while the
      oligosaccharides in the intravesicular compartment remained unchanged, as
      measured by streptolysin O permeabilization. This inhibition was furthermore
      selective in that it affected solely the components terminating in a single N
      acetylglucosamine residue (OS-GlcNAc(1)) and not the oligosaccharides terminating
      in a di-N-acetylchitobiose sequence (OS-GlcNAc(2)), which reside primarily in the
      intravesicular compartment. Despite the quantitative effect of the proteasome
      inhibitors on the cytosolic oligosaccharides, the molar distribution of the
      triglucosyl OS-GlcNAc(1) species was unaffected. The decrease in cytosolic
      oligosaccharides brought about by proteasome inhibition was reflected in a
      pronounced increase in the stability of the TCRalpha subunit. Our findings
      suggest that the N-deglycosylation and proteasome mediated degradation are
      coupled events. On the basis of our data and those of others we propose that the
      quality control mechanism involves proteasomes associated with the cytosolic side
      of the endoplasmic reticulum acting in concert with a membrane situated N
      glycanase. Such a complex by removing the carbohydrate units could facilitate the
      retrograde ER to cytosol translocation of glycoproteins.

PMID- 10910978
TI  - Reduction of the major xenoantigen on glycosphingolipids of swine endothelial
      cells by various glycosyltransferases.
AB  - The effect of the various glycosyltransferases on glycosphingolipids was
      examined, using transfected swine endothelial cell (SEC) lines. The reactivity of
      parental SEC to normal human serum (NHS) and Griffonia simplicifolia IB(4)
      (GSIB4) lectin, which binds to the Gal alpha1-3 Gal beta 1-4 GlcNAc-R (alpha
      galactosyl epitope), was reduced by approximately 20% by the treatment with D
      PDMP (D-threo-1-phenyl-2-decan- oylamino-3-morpholino-1-propanol), suggesting
      that glycosphingolipids contained by SEC have a considerable amount of the alpha
      galactosyl epitope. The overexpression of two different types of
      glycosyltransferase, N-acetylglucosaminyl transferase III (GnT-III), as well as
      alpha2, 6-sialyltransferase (ST6Gal I), alpha2,3-sialyltransferase (ST3Gal III),
      and alpha1,2-fucosyltransferase (alpha1,2FT), suppresses the total antigenicity
      of SEC significantly. However, the reduction in reactivities toward NHS and GSIB4
      lectin in the case of GnT-III transfectants was milder than those in other
      transfectants. Western blot analysis indicated that the glycoproteins in all
      transfectants had diminished reactivity to NHS and GSIB4 lectin to approximately
      the same extent. Therefore, the neutral glycosphingolipids of these transfectants
      were separated by thin layer chromatography, followed by immunostaining with NHS
      and GSIB4 lectin. The levels of the alpha-galactosyl epitope in
      glycosphingolipids were not decreased in the GnT-III transfectants but were in
      the ST6Gal I, ST3Gal III, and alpha1,2FT transfectants. These data indicate that
      ST6Gal I, ST3Gal III, and alpha1,2FT reduced the alpha-galactosyl epitope in both
      glycoproteins and glycosphingolipids, while GnT-III reduced them only in
      glycoproteins.

PMID- 10910977
TI  - Evidence for interaction of yeast protein kinase C with several subunits of
      oligosaccharyl transferase.
AB  - Oligosaccharyltransferase (OT) in Saccharomyces cerevisiae is an enzyme complex
      consisting of 8 transmembrane proteins located in the endoplasmic reticulum (ER).
      Studies on potential protein-protein interactions in OT using a two-hybrid
      library screen revealed that protein kinase C (Pkc1p) interacted with the lumenal
      domains of several OT subunits. Additional genetic experiments revealed that
      overexpression of two OT subunits rescued the growth defect caused by
      overexpression of a Pkc1 active site mutant, implying that there are specific
      genetic interactions between PKC1 and OT. These in vivo findings were
      complemented by in vitro studies that showed that several of the OT subunits
      bound to a fusion protein consisting of glutathione S-transferase linked via its
      C-terminus to Pkc1p. Assays of OT activity, in which glycosylation of a simple
      acceptor peptide was assayed in microsomes from wild-type and a pkc1 null
      revealed a 50% reduction in activity in the microsomes from the null strain. In
      contrast, strains containing null mutations of two other genes known to be
      downstream of Pkc1p in the PKC1-MAP kinase pathway had a level of OT activity
      comparable to that of wild-type cells. These in vivo and in vitro experiments
      suggest that in yeast cells Pkc1p may be involved in regulation of the N
      glycosylation of proteins.

PMID- 10910980
TI  - Response

PMID- 10910979
TI  - Bisphenol A and related endocrine disruptors.
AB  - The article highlighted in this issue is "Bisphenol A-Induced Increase in Uterine
      Weight and Alterations in Uterine Morphology in Ovariectomized B6C3F1 Mice: Role
      of the Estrogen Receptor" by Andriana D. Papaconstantinou, Thomas H. Umbreit,
      Benjamin R. Fisher, Peter L. Goering, Nicholas T. Lappas, and Ken M. Brown (pp.
      332-339).

PMID- 10910981
TI  - Gerhard Zbinden, 1924-1993.

PMID- 10910982
TI  - Metals and disorders of cell accumulation: modulation of apoptosis and cell
      proliferation.

PMID- 10910983
TI  - Evaluation of percutaneous penetration of natural rubber latex proteins.
AB  - Latex allergy is recognized worldwide as a serious health risk. To date, exposure
      assessment and intervention strategies have focused primarily on respiratory
      protection; this work evaluates the potential role of dermal protein penetration
      in the development of latex allergy. In vitro penetration models using flow
      through diffusion cells and both human surgical specimens and hairless guinea pig
      skin (CrL: IAF/HA) demonstrated iodinated latex proteins (ammoniated and non
      ammoniated) penetrating into and through both intact and abraded skin. Although
      less than 1% penetration was observed with intact skin, up to 23% of latex
      proteins applied to abraded skin were recovered from receptor fluid within 24 h
      of exposure. Phosphoimaging of the concentrated effluent revealed proteins
      ranging in size from 3 to 26 kDa. Using a (3)H(2)O penetration assay to evaluate
      barrier integrity, the amount of latex protein penetration was found to
      positively correlate with the degree of dermabrasion. Immunohistochemistry of the
      skin localized latex proteins in the Langerhans cell-rich epidermis and in the
      dermis. Both in vitro penetration studies and immunohistochemistry supported the
      use of hairless guinea pig skin as a surrogate for human skin in evaluating latex
      protein penetration. In studies performed in vivo, 35% of hairless guinea pigs
      topically exposed to latex proteins (100 microg) 5 days per week for 3 months
      demonstrated elevations in latex-specific IgG1. The implication for these data is
      that the skin is not only a plausible route for latex sensitization but can be a
      major exposure route when the integument has been compromised.

PMID- 10910984
TI  - Toxicokinetics of phenolphthalein in male and female rats and mice.
AB  - Phenolphthalein (PTH), which has been used as the active ingredient in a number
      of prescription and over-the-counter laxative products, is a rodent chemical
      carcinogen in multiple organs in the NTP 2-year bioassay at doses of 291-2927
      mg/kg. This paper describes the toxicokinetics and estimates the internal dose of
      PTH administered as a single iv or gavage dose, or ad libitum for 14 days in feed
      to F344 rats, B6C3F1 mice, p53 (+/-) mice, and C57BL mice at doses that bracketed
      those used in the bioassay. Plasma concentrations for free phenolphthalein (PTH
      F) and phenolphthalein glucuronide (PTH-G) were obtained for each dose regimen.
      Total phenolphthalein (PTH-T) was calculated as the sum of the molar
      concentrations of PTH-F and PTH-G. Noncompartmental pharmacokinetic models were
      used to calculate the area under the curve (AUC) from 0 h to infinity
      (AUC(infinity)), clearance (Cl), and oral bioavailability (F) for PTH-F; and were
      used to calculate AUC(infinity), t((1/2)), and relative absorption (Q) for PTH-T.
      After iv administration, PTH-F rapidly declined in rats and mice; PTH-T rose
      rapidly to Cmax and slowly declined 6-8 h after dosing, with no sex-related
      differences for rats or mice. For feed studies, mean plasma concentration
      (f1.gif" BORDER="0">(infinity)) and 24-h area under the curve (AUC(24h)) values
      were calculated. Results from feed studies showed no dose response in rat plasma
      PTH-F above approximately 50 mg/kg. Rat PTH-T AUC(24h) and f1.gif"
      BORDER="0">(infinity) were linear with doses up to approximately 650 mg/kg. In
      B6C3F1 mice, PTH-F and PTH-T AUC(24h) increased nonlinearly with doses above
      approximately 165 mg/kg. PTH is well absorbed and readily converted to PTH-G when
      administered in feed to rats and mice, except at the highest bioassay doses,
      where PTH absorption may be saturated.

PMID- 10910985
TI  - The disinfection by-products dichloro-, dibromo-, and bromochloroacetic acid
      impact intestinal microflora and metabolism in Fischer 344 rats upon exposure in
      drinking water.
AB  - Human consumption of chlorinated drinking water has been linked epidemiologically
      to bladder, kidney, and rectal cancers. The disinfection by-product (DBP)
      dichloroacetic acid is a hepatocarcinogen in Fischer 344 rats and B6C3F1 mice.
      The objective of this study is to determine the effect of the DBPs dichloro-,
      bromochloro-, and dibromoacetic acids (DCA, BCA, DBA) on intestinal microbial
      populations and their metabolism, with emphasis on enzymes involved in the
      bioactivation of procarcinogens and promutagens. One-month-old male Fischer 344
      rats were provided water ad libitum containing 1 g/l DCA, BCA, or DBA for up to 5
      weeks. At 1, 3, and 5 weeks of treatment, beta-glucuronidase (GLR), beta
      galactosidase (GAL), beta-glucosidase (GLU), nitroreductase (NR), azoreductase
      (AR), and dechlorinase (DC) activities were determined in cecal and small and
      large intestinal homogenates. After 5 weeks of treatment, intestinal populations
      were enumerated on selective media. Cecal GAL (DCA, BCA, DBA) and GLR (DCA, DBA)
      activities were reduced after 1 and 3 weeks of treatment and GAL activity was
      elevated at 5 weeks (BCA). Large intestinal GAL (DCA, BCA) and GLU (DCA, BCA,
      DBA) activities were elevated after 5 weeks of treatment. Week 5 cecal AR (DCA,
      BCA, DBA), NR (DCA), and DC (DCA, DBA) activities were reduced. Even though some
      significant changes in intestinal populations were observed, use of selective
      media was not sensitive enough to explain fluctuations in enzyme activity.
      Haloacetic acids in the drinking water alter intestinal metabolism, which could
      influence bioactivation of promutagens and procarcinogens in the drinking water.

PMID- 10910986
TI  - Possible relationship between phototoxicity and photodegradation of sitafloxacin,
      a quinolone antibacterial agent, in the auricular skin of albino mice.
AB  - We compared the phototoxic potential of the quinolone antibacterial agent
      sitafloxacin with those of lomefloxacin and sparfloxacin. Female BALB/c mice were
      given a single intravenous administration of sitafloxacin, lomefloxacin, or
      sparfloxacin at 10 or 40 mg/kg, followed by ultraviolet-A (UVA) irradiation for 4
      h (21.6 J/cm(2)). At 10 mg/kg, all quinolones induced either none or minimum
      inflammation in the auricle. At 40 mg/kg, sitafloxacin induced mild phototoxic
      inflammation in the dermal skin, while lomefloxacin and sparfloxacin induced very
      severe inflammation. In particular, 2/5 animals of the lomefloxacin group showed
      partial necrosis in the dermis and epidermis. We then determined the time course
      change of sitafloxacin concentrations in serum and auricular tissue by high
      performance liquid chromatography. Sitafloxacin concentrations in the auricle
      were markedly decreased under UVA irradiation, whereas those in sera were not
      affected. Furthermore, we examined the severity of sitafloxacin-induced
      phototoxicity under varied duration of UVA irradiation. The severity of
      phototoxicity increased with increasing duration of UVA irradiation, and
      statistical analysis showed a close correlation between the severity and the
      decreased area under the drug concentration curve under UVA irradiation
      (DeltaAUC(auricle)). The severity was decreased with delay in commencement of UVA
      irradiation, indicating the importance of commencement time of irradiation in the
      experimental condition of the phototoxicity study. It might be attributed to the
      decrease in DeltaAUC(auricle) after administration. These results suggest that
      sitafloxacin possesses milder phototoxic potential than lomefloxacin or
      sparfloxacin and is degraded in the auricular skin under UVA irradiation, and
      that the severity of phototoxicity is directly proportional to the
      DeltaAUC(auricle).

PMID- 10910987
TI  - Correlation between Bcl-2 overexpression and H-ras mutation in naturally
      occurring hepatocellular proliferative lesions of the B6C3F1 mouse.
AB  - The correlation between the mutation at codon 61 of the H-ras gene and the
      expression of the Bcl-2 protein was investigated in naturally occurring
      hepatocellular proliferative lesions in B6C3F1 mice. Specimens of histologically
      diagnosed neoplastic or preneoplastic lesions of the liver, obtained from the
      control mice used for 2-year carcinogenicity studies, were examined by
      immunohistochemical techniques. All of 25 lesions confirmed to be hepatocellular
      carcinomas stained positive for the Bcl-2 protein. Three of 12 foci of cellular
      alterations, as well as 24 of 42 hepatocellular adenomas, stained weakly
      positive. Bcl-2 protein was expressed to a greater degree in hepatocellular
      carcinomas as opposed to adenomas and confirmed by Western blot analysis. Seven
      of 18 hepatocellular adenomas that stained positive for Bcl-2 and three of 16
      hepatocellular adenomas that stained negative had a mutation at codon 61 of the H
      ras gene. Overexpression of Bcl-2 protein is likely to enhance the malignant
      turnover of the neoplastic cells, following a mutation at codon 61 of the H-ras
      gene particularly. These findings suggest that Bcl-2 overexpression and the
      mutation at codon 61 of the H-ras gene may be critical factors in the development
      of naturally occurring hepatocellular tumors in B6C3F1 mice.

PMID- 10910988
TI  - Morphological transformation by 8-hydroxy-2'-deoxyguanosine in Syrian hamster
      embryo (SHE) cells.
AB  - 8-Hydroxy-2'-deoxyguanosine (OH8dG) is one of the most prevalent oxidative DNA
      modifications found in eukaryotic cells. Previous studies have suggested an
      association between OH8dG formation and carcinogenesis. However, it is unclear
      whether OH8dG formation results in the necessary genotoxic events for cancer
      development. In the present study, the formation of OH8dG and its ability to
      transform Syrian hamster embryo (SHE) cells was examined. Methylene blue, a
      photosensitizer that in the presence of light can generate singlet oxygen by a
      type II mechanism, was used to produce oxidative DNA damage (predominantly OH8dG)
      in SHE cells. Photoactivated methylene blue produced a dose-dependent increase in
      OH8dG as well as a dose-dependent increase in morphological transformation in SHE
      cells. SHE cells transfected with DNA that contained increasing concentrations of
      OH8dG displayed a dose-dependent increase in morphological transformation.
      Treatment with beta-carotene (a singlet oxygen quencher) inhibited both the
      formation of OH8dG and the induction of morphological transformation in
      photoactivated methylene blue-treated SHE cells. These results suggest that
      formation of OH8dG can induce morphological transformation and provide further
      support for a role of OH8dG formation in the carcinogenesis process.

PMID- 10910990
TI  - Differential modulation of catecholamines by chlorotriazine herbicides in
      pheochromocytoma (PC12) cells in vitro.
AB  - Epidemiological, wildlife, and laboratory studies have pointed to the possible
      adverse health effects of chlorotriazine herbicide (i.e. , atrazine, simazine,
      and cyanazine) exposure. However, the cellular mechanism(s) of action of these
      compounds remains unknown. Recently, it was reported by Cooper et al. (2000,
      Toxicol. Sci. 53, 297-307) that atrazine disrupts ovarian function by altering
      hypothalamic catecholamine concentrations and subsequently the regulation of
      luteinizing hormone (LH) and prolactin (PRL) secretion by the pituitary. In this
      study, we examined the effect of three chlorotriazines on catecholamine
      metabolism in vitro using PC12 cells. Intracellular norepinephrine (NE) and
      dopamine (DA) concentrations and spontaneous NE release were measured following
      treatment with different concentrations of atrazine, simazine (0, 12. 5, 25, 50,
      100, and 200 microM) and cyanazine (0, 25, 50, 100, and 400 microM) for 6, 12,
      18, 24, and 48 h. Atrazine and simazine significantly decreased intracellular DA
      concentration in a concentration-dependent manner. Intracellular NE concentration
      was also significantly decreased by 100 and 200 microM atrazine and 200 microM
      simazine. Similarly, there was a dose-dependent inhibition of NE release with 100
      and 200 microM concentrations of both compounds. Although 100 and 400 microM
      cyanazine increased intracellular NE concentration, 50, 100, and 400 microM
      cyanazine significantly increased NE release at 24 and 36 h. In contrast,
      intracellular DA concentration was decreased by cyanazine, but only at 400
      microM. The GABA(A)-receptor agonist, muscimol (0, 0.01, 0.1, and 1.0 microM) had
      no effect on either the release or on intracellular catecholamine concentrations
      from 6 through 24 h of treatment. Cell viability was somewhat lower in the groups
      exposed to 100 and 200 microM atrazine and simazine. However, the reduction in
      viability was significant only in the highest dose of atrazine used (200 microM)
      at 24 h. Cyanazine did not have an effect on the viability at any of the doses
      tested, and the cells were functional, even up to 48 h of exposure. These data
      indicate that both atrazine and simazine inhibit the cellular synthesis of DA
      mediated by the tyrosine hydroxylase (TH), and NE mediated by dopamine beta
      hydroxylase (DbetaH), and, as a result, there is a partial or significant
      inhibition of NE release. Cyanazine, on the other hand, stimulated the synthesis
      of intracellular NE, and not DA. Thus, chlorotriazine compounds presumably act at
      the enzymatic steps or sites of CA biosynthesis to modulate monoaminergic
      activity in PC12 cells.

PMID- 10910989
TI  - Low levels of expression of cytochromes P-450 in normal and cancerous fetal
      pancreatic tissues of hamsters treated with NNK and/or ethanol.
AB  - Previous studies from this laboratory have demonstrated that administration of
      the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
      (NNK) to pregnant hamsters results in tumors in the offspring. Whereas treatment
      with NNK alone caused mainly tumors in the respiratory tract of the treated
      offspring, cotreatment with ethanol (EtOH) and NNK shifted the site of tumor
      formation to the pancreas. In order to determine potential mechanisms for the
      cocarcinogenic effects of EtOH, the levels of NNK metabolites and expression of
      various CYPs implicated in the metabolic activation of NNK were determined in
      fetal liver and pancreas. NNK and its metabolite, 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanol (NNAL), were detected at low and variable levels in the fetal
      liver and pancreas, with an NNAL to NNK ratio greater than 20 in both organs.
      EtOH had no effect on the amount of metabolites found in either organ. Results
      obtained with the fetal liver samples, which served as a positive control,
      correlated very well with our previous studies demonstrating low levels of
      expression of several CYP isozymes at both the protein and RNA level. Western
      blot analysis showed low but detectable levels of CYP1A1, barely detectable
      levels of CYP2E1, and an absence of CYP1A2 and 2B family members in the fetal
      pancreas. RNA transcripts were undetectable by ribonuclease protection in the
      fetal pancreas, although readily seen in fetal liver samples. Treatment with NNK,
      EtOH, or both NNK and EtOH had small and variable effects on the levels of
      metabolism of NNK and expression of the isozymes. These findings suggest that
      alternative mechanisms may be responsible for transplacentally induced tumors in
      this model system.

PMID- 10910991
TI  - Bisphenol A-induced increase in uterine weight and alterations in uterine
      morphology in ovariectomized B6C3F1 mice: role of the estrogen receptor.
AB  - The ability of the environmental xenoestrogen bisphenol A (BPA) to increase
      uterine wet weight in the rodent remains controversial, and few studies have
      previously examined the effects of BPA on uterine morphology. Furthermore, it is
      not known whether BPA-induced uterotrophic effects are, similarly to beta
      estradiol (E(2)), mediated through the estrogen receptor (ER). In this study, we
      compared the effects of BPA on uterine wet weight and morphology to those of E(2)
      in the B6C3F1 ovariectomized mouse. To examine whether these effects were
      mediated through the ER, the antiestrogen ICI 182, 780 (ICI) was co-administered
      with BPA or E(2). We report that subcutaneous administration of BPA at doses
      between 0.8 and 8 mg/day over 4 days significantly increased mean uterine wet
      weights above those of vehicle (corn oil)-treated mice. The uterine weight data
      suggest that BPA acts as a partial agonist with an EC(50) of 0.72 mg/day compared
      to 19.4 ng/day for E(2). BPA (2 mg/day) and E(2) (40 ng/day) induced a
      significant increase in luminal epithelial height and in the thickness of both
      the stromal and myometrial layers of the uterus. The effects of 40 ng E(2)/day on
      all endpoints studied were reversed by 20 microg ICI/day. ICI at 200, but not 20
      microg/day, was able to reverse the BPA (2 mg/day)-induced increase in both
      uterine wet weight and luminal epithelial height. ICI alone at 200 microg/day
      stimulated an increase in thickness of both the stroma and myometrium and did not
      reverse the effects of BPA (2 mg/day) on these layers. These results suggest that
      the BPA-induced increase in uterine wet weight and in luminal epithelial height
      in the ovariectomized B6C3F1 mouse are mediated by the ER.

PMID- 10910992
TI  - The effects of TCDD on the activation of ovalbumin (OVA)-specific DO11.10
      transgenic CD4(+) T cells in adoptively transferred mice.
AB  - Exposure to the environmental contaminant 2,3,7, 8-tetrachlorodibenzo-p-dioxin
      (TCDD) suppresses the generation of T cell-dependent immunity, both humoral and
      cell-mediated. However, the mechanism of TCDD-induced immune suppression remains
      to be defined. We hypothesized that exposure to TCDD suppresses the activation of
      naive CD4(+) T cells and prevents their expansion and differentiation into
      effector T-helper cells capable of driving T cell-dependent immune responses. To
      test this hypothesis, we adoptively-transferred DO11.10 OVA-specific T-cell
      receptor (TCR) transgenic T cells into syngeneic recipients and used a TCR
      specific monoclonal antibody to track the in vivo activation of naive CD4(+) T
      lymphocytes following exposure to OVA. The production of OVA-specific antibodies
      was suppressed in a dose-dependent manner in adoptively transferred mice that had
      been exposed to TCDD. Although TCDD exposure had little effect on the expansion
      or activation of the adoptively transferred, OVA-specific CD4(+) T cells, these
      cells disappeared from the spleen more rapidly in TCDD-treated mice and produced
      significantly decreased levels of the T cell-derived cytokines IL-2 and IL-10.
      There was also a trend towards reduced IFN-gamma and IL-4 production following in
      vitro re-stimulation. These data suggest that TCDD may interfere with the
      survival and/or differentiation of OVA-specific T-helper cells. These results
      demonstrate for the first time the potential of the DO11.10 adoptive transfer
      system to directly assess immunotoxic effects of xenobiotics on antigen-specific
      CD4(+) T cells in vivo.

PMID- 10910993
TI  - Mutagenicity studies of benzidine and its analogs: structure-activity
      relationships.
AB  - The Ames Salmonella/microsome assay was employed to test the mutagenicity of
      benzidine and its analogs using strains TA98 and TA100 in the presence and
      absence of Aroclor 1254-induced rat S9 mix. 3,3'-Dichlorobenzidine-2HCl and 4,4'
      dinitro-2-biphenylamine were directly mutagenic to TA98, while 4,4'-dinitro-2
      biphenylamine was directly mutagenic to both TA98 and TA100 in the absence of S9
      mix. 2-Aminobiphenyl, 3-aminobiphenyl, and 3,3'-5,5'-tetramethylbenzidine were
      not mutagenic in either strains in the presence or absence of S9. In the presence
      of S9 mix, 4-aminobiphenyl, benzidine, 3, 3'-dichlorobenzidine-2HCl, 3,3'
      dimethoxybenzidine, 3,3'-4, 4'-tetraaminobiphenyl, o-tolidine, N, N-N', N'
      tetramethylbenzidine, and 4,4'-dinitro-2-biphenylamine were mutagenic to TA98; 4
      aminobiphenyl, 3,3'-dichlorobenzidine-2HCl, 3, 3'-dimethoxybenzidine, and 4,4'
      dinitro-2-biphenylamine were mutagenic to TA100. Physicochemical parameters of
      these compounds including oxidation potentials, the energy difference between the
      lowest unoccupied molecular orbital and the highest occupied molecular orbital,
      ionization potentials, dipole moment, relative partition coefficient, and
      basicity did not correlate with their bacterial mutagenic activities.

PMID- 10910994
TI  - TCDD suppression of tissue transglutaminase stimulation by retinoids in malignant
      human keratinocytes.
AB  - The human keratinocyte line SCC-4 is a model system in which to explore the
      mechanism by which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with the
      action of hormones in the steroid receptor superfamily. In present work, retinoid
      induction of tissue transglutaminase mRNA was suppressed 60-70% by 10 nM TCDD in
      the human squamous carcinoma cell line SCC-4. This effect occurred without
      enhanced degradation of the mRNA and thus appeared to result from altered
      transcription. The actions of all-trans-retinoic acid and the synthetic retinoid
      TTNPB ((E)4-[2-(5,6,7,8-tetrahydro-5,5,8, 8-tetramethyl-2-naphthylenyl)
      1propenyl] benzoic acid), which resists metabolic degradation, were suppressed to
      the same extent without obvious changes in their EC(50)s. In addition, TCDD
      suppression of reporter transcription, driven by a retinoic acid response
      element, was not evident in transient or stable transfections of SCC-4 cells.
      Sodium butyrate (3 mM) alone induced tissue transglutaminase and augmented
      retinoid induction. In the presence of butyrate, TCDD acted as an inducer and did
      not reduce retinoid stimulation. Retinoic acid induction of tissue
      transglutaminase displayed a lag phase of >24 h, indicating that the induction
      has an indirect component. Rather than depleting active retinoid in the culture
      medium or generally inactivating retinoid receptor function, TCDD may suppress
      retinoid action in this case by interfering with the late phase of induction.

PMID- 10910995
TI  - Biphasic effects of 1,1,1-trichloroethane on the locomotor activity of mice:
      relationship to blood and brain solvent concentrations.
AB  - Despite the central nervous system (CNS) being a target of virtually all
      solvents, few solvents have been thoroughly studied for their effects on
      unlearned animal behaviors. Of the solvents that have been studied, little is
      known about the relationship of exposure concentration to behavioral effect, and
      quantitative data relating the toxicologically important target organ (i.e.,
      brain) dose to behavioral effect are almost non-existent. To examine the
      concentration- and time-dependency of effects of 1,1, 1-trichloroethane (TRI) on
      behavior, male albino Swiss-Webster mice were exposed to TRI (500-14,000 ppm) in
      static inhalation chambers for 30 min, during which locomotor activity was
      measured. Separate mice were exposed to the same concentrations under identical
      conditions for 6, 12, 18, 24, and 30 min, to determine blood and brain
      concentrations versus time profiles for TRI. This allowed for the relationships
      between blood and brain concentrations of TRI and locomotor activity to be
      discerned. The lowest TRI concentrations studied (500-2000 ppm) had no
      statistically significant effect on activity, intermediate concentrations (4000
      8000 ppm) increased activity immediately to levels that remained constant over
      time, and higher concentrations (10,000-14,000 ppm) produced biphasic effects,
      i.e., increases in activity followed by decreases. 1,1, 1-Trichloroethane
      concentrations in blood and brain approached steady-state equilibria very
      rapidly, demonstrated linear kinetics, and increased in direct proportion to one
      another. Locomotor activity increased monophasically ( approximately 3.5-fold) as
      solvent concentrations increased from approximately 50-150 microg/g brain and
      microg/ml blood. As concentrations exceeded the upper limit of this range, the
      activity level declined and eventually fell below the control activity level at
      approximately 250 microg/g brain and microg/ml blood. Regression analyses
      indicated that blood and brain concentrations during exposure were strongly
      correlated with locomotor activity, as were measures of internal dose integrated
      over time. The broad exposure range employed demonstrated that TRI, like some
      classical CNS depressants, is capable of producing biphasic effects on behavior,
      supporting the hypothesis that selected solvents are members of the general class
      of CNS depressant drugs. By relating internal dose measures of TRI to locomotor
      activity, our understanding of the effects observed and their predictive value
      may be enhanced.

PMID- 10910996
TI  - Subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin modulates the
      pathophysiology of endometriosis in the cynomolgus monkey.
AB  - An increase in the incidence and severity of endometriosis following treatment
      with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was a serendipitous finding in a
      reproductive toxicology study in rhesus monkeys. The purpose of this study was to
      investigate the effects of subchronic exposure to TCDD on the survival and growth
      of surgically implanted endometrial fragments. Endometrial fragments of equal
      size (4 x 1 mm(2)) were auto-transplanted to the pelvic cavity of nulliparous
      cynomolgus monkeys (Macaca fascicularis, n = 23), who were divided into 4
      treatment groups and dosed 5 days a week with gelatin capsules containing 0, 1,
      5, or 25 ng/kg body weight of TCDD mixed with glucose. Endometrial implant
      survival was monitored by laparoscopy at intervals of 1, 3, and 6 months. Animals
      were euthanized at 12 months of treatment in the early to mid luteal phase and
      the maximal and minimal endometrial implant diameter was measured. Both the
      maximal and minimal diameters were significantly reduced in the 0.71-ng/kg/day
      TCDD dose group, compared to controls, whereas the survival rate was unaffected
      (20 vs. 16%, respectively). In contrast, exposure to 3.57 and 17.86 ng/kg/day
      TCDD for 1 year resulted in a significantly higher survival rate of implants
      (26.7% and 33.3% respectively vs. 16.0%) and significantly larger diameter
      implants in the 17.86-ng/kg/day dose group only, compared to the control group.
      Treatment had no effect on circulating gonadal steroid levels or menstrual cycle
      characteristics. It is concluded that TCDD facilitates the survival of
      endometrial implants and exerts a bimodal effect on endometrial implant growth.

PMID- 10910997
TI  - Physiological role of the aryl hydrocarbon receptor in mouse ovary development.
AB  - The aryl hydrocarbon receptor (AhR) regulates the toxicity of environmental
      contaminants such as 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD). As the
      physiological role of the AhR in the ovary is unknown, the purpose of this study
      was to test the hypothesis that the AhR regulates the appearance and numbers of
      ovarian follicles. Ovaries were harvested from AhR-deficient (AhRKO) and wild
      type mice on gestational day 18 (GD 18) and postnatal days (PND) 2-3, 8, 32-35,
      and 53. Complete serial sections of ovaries were evaluated histologically for the
      presence of germ cells and follicles. On GD 18, there was no difference in the
      number of germ cells per ovary between AhRKO and wild-type fetuses. However, by
      PND 2-3, AhRKO mice had significantly more fully formed primordial follicles
      (AhRKO = 38,440 +/- 3632 versus wild-type = 21,120 +/- 2688) and fewer single
      germ cells than wild-type mice (AhRKO = 12,696 +/- 1192 vs. wild-type = 18,160 +/
      720). On PND 8 and 32-35, there was no difference in the number of follicles
      between AhRKO and wild-type mice but by PND 53, AhRKO mice had significantly
      fewer antral follicles than wild-type (AhRKO = 3416 +/- 480 vs. wild-type = 6776
      +/- 1024). Taken together, these results suggest that the AhR may play a role in
      the formation of primordial follicles and the regulation of antral follicle
      numbers.

PMID- 10910998
TI  - Cellular and molecular mechanisms of action of linuron: an antiandrogenic
      herbicide that produces reproductive malformations in male rats.
AB  - Antiandrogenic chemicals alter sex differentiation by several different
      mechanisms. Some, like flutamide, procymidone, or vinclozolin compete with
      androgens for the androgen receptor (AR), inhibit AR-DNA binding, and alter
      androgen-dependent gene expression in vivo and in vitro. Finasteride and some
      phthalate esters demasculinize male rats by inhibiting fetal androgen synthesis.
      Linuron, which is a weak competitive inhibitor of AR binding (reported Ki of 100
      microM), alters sexual differentiation in an antiandrogenic manner. However, the
      pattern of malformations more closely resembles that produced by the phthalate
      esters than by vinclozolin treatment. The present study was designed to determine
      if linuron acted as an AR antagonist in vitro and in vivo. In vitro, we (1)
      confirmed the affinity of linuron for the rat AR, and found (2) that linuron
      binds human AR (hAR), and (3) acts as an hAR antagonist. Linuron competed with an
      androgen for rat prostatic AR (EC(50) = 100-300 microM) and human AR (hAR) in a
      COS cell-binding assay (EC(50) = 20 microM). Linuron inhibited
      dihydrotestosterone (DHT)-hAR induced gene expression in CV-1 and MDA-MB-453-KB2
      cells (EC(50) = 10 microM) at concentrations that were not cytotoxic. In short
      term in vivo studies, linuron treatment reduced testosterone- and DHT-dependent
      tissue weights in the Hershberger assay (oral 100 mg/kg/d for 7 days, using
      castrate-immature-testosterone propionate-treated male rats; an assay used for
      decades to screen for AR agonists and antagonists) and altered the expression of
      androgen-regulated ventral prostate genes (oral 100 mg/kg/d for 4 days).
      Histological effects of in utero exposure to linuron (100 mg/kg/d, day 14-18) or
      DBP (500 mg/kg/d, day 14 to postnatal day 3) on the testes and epididymides also
      are shown here. Taken together, these results support the hypothesis that linuron
      is an AR antagonist both in vivo and in vitro, but it remains to be determined if
      linuron alters sexual differentiation by additional mechanisms of action.

PMID- 10910999
TI  - Neonatal exposure of male rats to nonylphenol has no effect on the reproductive
      tract.
AB  - P. C. Lee (1998, ENDOCRINE: 9, 105-111) has reported that neonatal exposure of SD
      rats to nonylphenol (NP; 8 mg/kg/day) by daily intraperitoneal (ip) injection in
      DMSO results in decreased ventral prostate and epididymides weights, and delayed
      testes descent, at post natal day (pnd) 31. These effects were surprising given
      that similar effects were not reported in an earlier multi-generation study of
      NP. We have repeated the central experiment described by Lee and were unable to
      confirm the effects reported. Alpk (Wistar derived) rats were exposed to NP
      (8mg/kg/day by ip injection in either arachis oil or DMSO) from pnd 1-10 and
      assessed on pnd 34-36. No significant effects on animal body weights were
      observed. The weights of the epididymides, seminal vesicles, testes, and ventral
      prostate were unaffected using either vehicle. Testes descent proceeded normally,
      with both test and control testes fully descended by pnd 29. Possible reasons for
      this divergence in findings for NP are discussed.

PMID- 10911000
TI  - Pulmonary chemokine and mutagenic responses in rats after subchronic inhalation
      of amorphous and crystalline silica.
AB  - Chronic inhalation of crystalline silica can produce lung tumors in rats whereas
      this has not been shown for amorphous silica. At present the mechanisms
      underlying this rat lung tumor response are unknown, although a significant role
      for chronic inflammation and cell proliferation has been postulated. To examine
      the processes that may contribute to the development of rat lung tumors after
      silica exposure, we characterized the effects of subchronic inhalation of
      amorphous and crystalline silica in rats. Rats were exposed for 6 h/day, on 5
      days/week, for up to 13 weeks to 3 mg/m(3) crystalline or 50 mg/m(3) amorphous
      silica. The effects on the lung were characterized after 6.5 and 13 weeks of
      exposure as well as after 3 and 8 months of recovery. Exposure concentrations
      were selected to induce high pulmonary inflammatory-cell responses by both
      compounds. Endpoints characterized after silica exposure included mutation in the
      HPRT gene of isolated alveolar cells in an ex vivo assay, changes in
      bronchoalveolar lavage fluid markers of cellular and biochemical lung injury and
      inflammation, expression of mRNA for the chemokine MIP-2, and detection of
      oxidative DNA damage. Lung burdens of silica were also determined. After 13 weeks
      of exposure, lavage neutrophils were increased from 0.26% (controls) to 47 and
      55% of total lavaged cells for crystalline and amorphous silica, with
      significantly greater lavage neutrophil numbers after amorphous silica (9.3 x
      10(7) PMNs) compared to crystalline silica (6.5 x 10(7) PMNs). Lung burdens were
      819 and 882 microg for crystalline and amorphous silica, respectively. BAL fluid
      levels of LDH as an indicator of cytotoxicity were twice as high for amorphous
      silica compared to those of crystalline silica, at the end of exposure. All
      parameters remained increased for crystalline silica and decreased rapidly for
      amorphous silica in the 8-month recovery period. Increased MIP-2 expression was
      observed at the end of the exposure period for both amorphous and crystalline
      silica. After 8 months of recovery, those markers remained elevated in
      crystalline silica-exposed rats, whereas amorphous silica-exposed rats were not
      significantly different from controls. A significant increase in HPRT mutation
      frequency in alveolar epithelial cells was detected immediately after 13 weeks of
      exposure to crystalline, but not to amorphous silica. A significant increase in
      TUNEL staining was detected in macrophages and terminal bronchiolar epithelial
      cells of amorphous silica-exposed rats at the end of the exposure period;
      however, crystalline silica produced far less staining. The observation that
      genotoxic effects in alveolar epithelial cells occurred only after crystalline
      but not amorphous silica exposure, despite a high degree of inflammatory-cell
      response after subchronic exposure to both types of silica, suggests that in
      addition to an inflammatory response, particle biopersistence, solubility, and
      direct or indirect epithelial cell cytotoxicity may be key factors for the
      induction of either mutagenic events or target cell death.

PMID- 10911001
TI  - Toxicity of tetrafluoroethylene and S-(1,1,2, 2-tetrafluoroethyl)-L-cysteine in
      rats and mice.
AB  - Groups of 25 female F344 rats and 25 female B6C3F1 mice were exposed to 0, 30,
      300, 600, or 1200 ppm tetrafluoroethylene (TFE) by inhalation for up to 12 days.
      Another set of 25 female rats and 25 female mice of the same strains were given
      0, 5, 20, or 50 mg/kg of S-(1,1,2,2-tetrafluoroethyl)-L-cysteine (TFE-CYS) by
      oral gavage for 12 days. Both 12-day exposure regimens consisted of exposures for
      5 consecutive days, a weekend with no exposures, and 4 consecutive daily
      exposures following the weekend. Five animals per group were sacrificed after the
      first exposure, the fifth exposure, and the ninth exposure for evaluation of cell
      proliferation in the liver and kidney. The remaining animals in each group (up to
      10) were sacrificed after the ninth exposure (test day 12) for pathological
      evaluation of the liver, kidney, and spleen. Clinical pathology evaluations were
      performed on test day 11 or 12. Inhalation of TFE by rats and mice caused slight
      microscopic changes in the kidneys of rats and mice, but no histopathological
      changes in the liver. In the kidney, administration of TFE-CYS by gavage caused
      severe microscopic changes in rats, moderate-to-severe changes in mice, and no
      microscopic changes in the liver. Cell proliferation was increased in the kidneys
      of rats and mice given TFE by inhalation and TFE-CYS by gavage. TFE-CYS also
      caused increased liver weights and cell proliferation in the liver of rats and
      mice at the high doses. The cell proliferation response in the kidney and liver
      was transient in both species, being most pronounced after 5 days of exposure,
      and less evident or absent after 12 days of exposure. In the kidney, the cell
      proliferation and histopathologic response in rats was generally more pronounced
      than in mice. Kidney damage and cell proliferation were confined to the pars
      recta (P3) of the outer stripe of the outer medulla and medullary rays. Tubules
      in mice exposed to TFE and TFE-CYS had mostly regenerating cells by test day 12,
      while in rats the tubules still showed marked degeneration along with
      regeneration by the end of the study. The cortical labyrinth (P1 and P2 segments)
      was also affected at the 50 mg/kg dose of TFE-CYS in rats. Rats exposed to 50
      mg/kg TFE-CYS had a mild anemia, and rats exposed to 1200 ppm TFE had slight,
      biologically inconsequential decreases in erythrocyte mass that may have been
      compound-related. In spite of the rather pronounced histopathologic changes in
      the kidneys of rats exposed to TFE-CYS, there was no clinical chemistry evidence
      for decreased kidney function. Increased levels of urinary fluoride were present
      in rats exposed to 300 ppm and greater of TFE, and in rats exposed to 20 and 50
      mg/kg TFE-CYS. The spleen was not affected in this study. Overall, the results of
      this study suggest that effects of TFE could be attributed to the toxicity of TFE
      CYS over the course of a 2-week exposure, as all effects that were seen with TFE
      were also seen with TFE-CYS.

PMID- 10911002
TI  - Cytotoxicity assessment of Ma-huang (Ephedra) under different conditions of
      preparation.
AB  - Ma-huang is a traditional Chinese medicinal herb derived from EPHEDRA: sinica
      Stapf and other EPHEDRA: species, used to treat asthma, nose and lung congestion,
      and fever with anhidrosis. It contains 0.5-2.5% by weight of total alkaloids, of
      which ephedrine accounts for 30 to 90%. Recently, large amounts of ma-huang were
      used as a source of ephedrine in many dietary supplements formulated for weight
      reduction, because ephedrine has been found effective in inducing weight loss in
      diet-restricted obese patients. However, indiscriminate consumption of ma-huang
      containing products has resulted in many cases of poisoning, some of which were
      fatal. The objective of this study is to investigate the relative toxicity of ma
      huang extracted under different conditions. The toxicities of various extracts
      were assayed using MTT colorimetry on a battery of cell lines, while ephedrine
      alkaloids were analyzed with HPLC. The results are summarized as follows. (1) The
      cytotoxicity of all ma-huang extracts could not be totally accounted for by their
      ephedrine contents, suggesting the presence of other toxins in the extracts. (2)
      Grinding was a significant condition enhancing the toxicity of the extracts. (3)
      The relatively high sensitivity of the Neuro-2a cell line to the toxicity of ma
      huang extracts suggests that the toxic principles were acting on neuronal cells.
      (4) One condition to produce a ma-huang extract with high ephedrine-to-toxins
      ratio would be to boil the whole herb for two h.

PMID- 10911003
TI  - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with
      hyperinsulinemia and insulin resistance.
AB  - High exposures of Vietnam veterans to 2,3,7, 8-Tetrachlorodibenzo-p-dioxin, a
      dioxin contained in the herbicide mixture Agent Orange, have previously been
      demonstrated to be associated with an increased prevalence of diabetes and
      hyperinsulinemia in non-diabetic subjects. Sixty-nine persons were identified who
      were in good health and had normal glucose levels during glucose tolerance
      testing. These subjects lived within 25 miles of the Vertac/Hercules Superfund
      site located in Jacksonville, Arkansas. The blood sera lipid concentrations of
      TCDD for the 69 subjects ranged between 2 and 94 ppt. When subjects with blood
      sera lipid TCDD levels in the top 10% (TCDD > 15 ppt, n = 7) were compared to
      subjects with lower levels (2-15 ppt, n = 62), there were no group differences in
      age, obesity, gender distribution, total lipids, or glucose levels. However,
      plasma insulin concentrations, at fasting and 30, 60, and 120 min following a 75
      g glucose load, were significantly higher in the group with high blood TCDD
      levels. These finding could not be explained by other known risk factors for
      hyperinsulinemia. The finding of the TCDD-hyperinsulinemia relationship is
      consistent with studies of Vietnam veterans and suggests that high blood TCDD
      levels may cause insulin resistance.

PMID- 10911004
TI  - Islet transplantation in seven patients with type 1 diabetes mellitus using a
      glucocorticoid-free immunosuppressive regimen.
AB  - BACKGROUND: Registry data on patients with type 1 diabetes mellitus who undergo
      pancreatic islet transplantation indicate that only 8 percent are free of the
      need for insulin therapy at one year. METHODS: Seven consecutive patients with
      type 1 diabetes and a history of severe hypoglycemia and metabolic instability
      underwent islet transplantation in conjunction with a glucocorticoid-free
      immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab.
      Islets were isolated by ductal perfusion with cold, purified collagenase,
      digested and purified in xenoprotein-free medium, and transplanted immediately by
      means of a percutaneous transhepatic portal embolization. RESULTS: All seven
      patients quickly attained sustained insulin independence after transplantation of
      a mean (+/-SD) islet mass of 11,547+/-1604 islet equivalents per kilogram of body
      weight (median follow-up, 11.9 months; range, 4.4 to 14.9). All recipients
      required islets from two donor pancreases, and one required a third transplant
      from two donors to achieve sustained insulin independence. The mean glycosylated
      hemoglobin values were normal after transplantation in all recipients. The mean
      amplitude of glycemic excursions (a measure of fluctuations in blood glucose
      concentrations) was significantly decreased after the attainment of insulin
      independence (from 198+/-32 mg per deciliter [11.1+/-1.8 mmol per liter] before
      transplantation to 119+/-37 mg per deciliter [6.7+/-2.1 mmol per liter] after the
      first transplantation and 51+/-30 mg per deciliter [2.8+/-1.7 mmol per liter]
      after the attainment of insulin independence; P<0.001). There were no further
      episodes of hypoglycemic coma. Complications were minor, and there were no
      significant increases in lipid concentrations during follow-up. CONCLUSIONS: Our
      observations in patients with type 1 diabetes indicate that islet transplantation
      can result in insulin independence with excellent metabolic control when
      glucocorticoid-free immunosuppression is combined with the infusion of an
      adequate islet mass.

PMID- 10911005
TI  - Effect of lung-volume-reduction surgery in patients with severe emphysema.
AB  - BACKGROUND: Although many patients with severe emphysema have undergone lung
      volume-reduction surgery, the benefits are uncertain. We conducted a randomized,
      controlled trial of the surgery in patients with emphysema. Patients with
      isolated bullae were excluded because such patients are known to improve after
      bullectomy. METHODS: Potentially eligible patients were given intensive medical
      treatment and completed a smoking-cessation program and a six-week outpatient
      rehabilitation program before random assignment to surgery or continued medical
      treatment. After 15 patients had been randomized, the entry criteria were
      modified to exclude patients with a carbon monoxide gas-transfer value less than
      30 percent of the predicted value or a shuttle-walking distance of less than 150
      m, because of the deaths of 5 such patients (3 treated surgically and 2 treated
      medically). RESULTS: Of the 174 subjects who were initially assessed, 24 were
      randomly assigned to continued medical treatment and 24 to surgery. At base line
      in both groups, the median forced expiratory volume in one second (FEV1) was 0.75
      liter, and the median shuttle-walking distance was 215 m. Five patients in the
      surgical group (21 percent) and three patients in the medical group (12 percent)
      died (P=0.43). After six months, the median FEV1 had increased by 70 ml in the
      surgical group and decreased by 80 ml in the medical group (P=0.02). The median
      shuttle-walking distance increased by 50 m in the surgical group and decreased by
      20 m in the medical group (P=0.02). There were similar changes on a quality-of
      life scale and similar changes at 12 months of follow-up. Five of the 19
      surviving patients in the surgical group had no benefit from the treatment.
      CONCLUSIONS: In selected patients with severe emphysema, lung-volume-reduction
      surgery can improve FEV1, walking distance, and quality of life. Whether it
      reduces mortality is uncertain.

PMID- 10911006
TI  - Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated
      congestive heart failure. Nesiritide Study Group.
AB  - BACKGROUND: Intravenous infusion of nesiritide, a brain (B-type) natriuretic
      peptide, has beneficial hemodynamic effects in patients with decompensated
      congestive heart failure. We investigated the clinical use of nesiritide in such
      patients. METHODS: Patients hospitalized because of symptomatic congestive heart
      failure were enrolled in either an efficacy trial or a comparative trial. In the
      efficacy trial, which required the placement of a Swan-Ganz catheter, 127
      patients with a pulmonary-capillary wedge pressure of 18 mm Hg or higher and a
      cardiac index of 2.7 liters per minute per square meter of body-surface area or
      less were randomly assigned to double-blind treatment with placebo or nesiritide
      (infused at a rate of 0.015 or 0.030 microg per kilogram of body weight per
      minute) for six hours. In the comparative trial, which did not require
      hemodynamic monitoring, 305 patients were randomly assigned to open-label therapy
      with standard agents or nesiritide for up to seven days. RESULTS: In the efficacy
      trial, at six hours, nesiritide infusion at rates of 0.015 and 0.030 microg per
      kilogram per minute decreased pulmonary-capillary wedge pressure by 6.0 and 9.6
      mm Hg, respectively (as compared with an increase of 2.0 mm Hg with placebo,
      P<0.001), resulted in improvements in global clinical status in 60 percent and 67
      percent of the patients (as compared with 14 percent of those receiving placebo,
      P<0.001), reduced dyspnea in 57 percent and 53 percent of the patients (as
      compared with 12 percent of those receiving placebo, P<0.001), and reduced
      fatigue in 32 percent and 38 percent of the patients (as compared with 5 percent
      of those receiving placebo, P<0.001). In the comparative trial, the improvements
      in global clinical status, dyspnea, and fatigue were sustained with nesiritide
      therapy for up to seven days and were similar to those observed with standard
      intravenous therapy for heart failure. The most common side effect was dose
      related hypotension, which was usually asymptomatic. CONCLUSIONS: In patients
      hospitalized with decompensated congestive heart failure, nesiritide improves
      hemodynamic function and clinical status. Nesiritide is useful for the treatment
      of decompensated congestive heart failure.

PMID- 10911007
TI  - Preoperative staging of non-small-cell lung cancer with positron-emission
      tomography.
AB  - BACKGROUND: Determining the stage of non-small-cell lung cancer often requires
      multiple preoperative tests and invasive procedures. Whole-body positron-emission
      tomography (PET) may simplify and improve the evaluation of patients with this
      tumor. METHODS: We prospectively compared the ability of a standard approach to
      staging (computed tomography [CT], ultrasonography, bone scanning, and, when
      indicated, needle biopsies) and one involving PET to detect metastases in
      mediastinal lymph nodes and at distant sites in 102 patients with resectable non
      small-cell lung cancer. The presence of mediastinal metastatic disease was
      confirmed histopathologically. Distant metastases that were detected by PET were
      further evaluated by standard imaging tests and biopsies. Patients were followed
      postoperatively for six months by standard methods to detect occult metastases.
      Logistic-regression analysis was used to evaluate the ability of PET and CT to
      identify malignant mediastinal lymph nodes. RESULTS: The sensitivity and
      specificity of PET for the detection of mediastinal metastases were 91 percent
      (95 percent confidence interval, 81 to 100 percent) and 86 percent (95 percent
      confidence interval, 78 to 94 percent), respectively. The corresponding values
      for CT were 75 percent (95 percent confidence interval, 60 to 90 percent) and 66
      percent (95 percent confidence interval, 55 to 77 percent). When the results of
      PET and CT were adjusted for each other, only PET results were positively
      correlated with the histopathological findings in mediastinal lymph nodes
      (P<0.001). PET identified distant metastases that had not been found by standard
      methods in 11 of 102 patients. The sensitivity and specificity of PET for the
      detection of both mediastinal and distant metastatic disease were 95 percent (95
      percent confidence interval, 88 to 100 percent) and 83 percent (95 percent
      confidence interval, 74 to 92 percent), respectively. The use of PET to identify
      the stage of the disease resulted in a different stage from the one determined by
      standard methods in 62 patients: the stage was lowered in 20 and raised in 42.
      CONCLUSIONS: PET improves the rate of detection of local and distant metastases
      in patients with non-small-cell lung cancer.

PMID- 10911008
TI  - A molecular link between the sudden infant death syndrome and the long-QT
      syndrome.

PMID- 10911009
TI  - Images in clinical medicine. Lung cancer presenting as an ankle metastasis.

PMID- 10911010
TI  - Chronic obstructive pulmonary disease.

PMID- 10911011
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 23-2000. A 49-year-old man with the acquired immunodeficiency
      syndrome and a tibial lesion.

PMID- 10911012
TI  - Successful islet transplantation for patients with diabetes--fact or fantasy?

PMID- 10911013
TI  - Metabolic staging of lung cancer.

PMID- 10911015
TI  - Correction: Cytokeratin-Positive Cells in the Bone Marrow and Survival of
      Patients with Stage I, II, or III Breast Cancer.

PMID- 10911014
TI  - The rise and fall of the futility movement.

PMID- 10911016
TI  - Novel approaches for designing 5'-O-ester prodrugs of 3'-azido-2', 3'
      dideoxythymidine (AZT).
AB  - 3'-Azido-2',3'-dideoxythymidine (AZT, 1, zidovudine, RetrovirTM) is used to treat
      patients with human immunodeficiency virus (HIV) infection. AZT, after conversion
      to AZT-5'-triphosphate (AZT-TP) by cellular enzymes, inhibits HIV-reverse
      transcriptase (HIV-RT). The major clinical limitations of AZT are due to clinical
      toxicities that include bone marrow suppression, hepatic abnormalities and
      myopathy, absolute dependence on host cell kinase-mediated activation which leads
      to low activity, limited brain uptake, a short half-life of about one hour in
      plasma that dictates frequent administration to maintain therapeutic drug levels,
      low potential for metabolic activation and/or high susceptibility to catabolism,
      and the rapid development of resistance by HIV-1. These limitations have prompted
      the development of strategies for designing prodrugs of AZT. A variety of 5'-O
      substituted prodrugs of AZT constitute the subject of this review. The drug
      design rationale on which these approaches are based is that the ester conjugate
      will be converted by hydrolysis and/or enzymatic cleavage to AZT or its 5&prime;
      monophosphate (AZT-MP). Most prodrug derivatives of AZT have been prepared by
      derivatization of AZT at its 5'-O position to provide two prominent classes of
      compounds that encompass: A) 5'-O-carboxylic esters derived from 1) cyclic 5'-O
      carboxylic acids such as steroidal 17b-carboxylic acids, 1-adamantanecarboxylic
      acid, bicyclam carboxylic acid derivatives, O-acetylsalicylic acid, and
      carbohydrate derivatives, 2) amino acids, 3) 1, 4-dihydro-1-methyl-3
      pyridinylcarboxylic acid, 4) aliphatic fatty acid analogs such as myristic acid
      containing a heteroatom, or without a heteroatom such as stearic acid, and 5)
      long chain polyunsaturated fatty acid analogs such as retinoic acid, and B)
      masked phosphates such as 1) phosphodiesters that include monoalkyl or monoaryl
      phosphate, carbohydrate, ether lipid, ester lipid, and foscarnet derivatives, 2)
      a variety of phosphotriesters that include dialkylphosphotriesters,
      diarylphosphotriesters, glycolate and lactate phosphotriesters, phosphotriester
      approaches using simultaneous enzymatic and chemical hydrolysis of bis(4
      acyloxybenzyl) esters, bis(S-acyl-2-thioethyl) (SATE) esters, cyclosaligenyl
      prodrugs, glycosyl phosphotriesters, and steroidal phosphotriesters, 3)
      phosphoramidate derivatives, 4) dinucleoside phosphate derivatives that possess a
      second anti-HIV moiety such as AZT-P-ddA, AZT-P-ddI, AZTP2AZT, AZTP2ACV), and 5)
      5'-hydrogen phosphonate and 5'-methylene phosphonate derivatives of AZT. In these
      prodrugs, the conjugating moiety is linked to AZT via a 5'-O-ester or 5'-O
      phosphate group. 5'-O-Substituted AZT prodrugs have been designed with the
      objectives of improving anti-HIV activity, enhancing blood-brain barrier
      penetration, modifying pharmacokinetic properties to increase plasma half-life
      and improving drug delivery with respect to site-specific targeting or drug
      localization. Bypassing the first phosphorylation step, regulating transport and
      conferring sustained release of AZT prolong its duration of action, decrease
      toxicity and improve patient acceptability. The properties of these prodrugs and
      their anti-HIV activities are now reviewed.

PMID- 10911017
TI  - Recent advances in inducible cyclooxygenase (COX-2) inhibition.
AB  - Cyclooxygenase is the key enzyme in the biosynthesis of prostanoids, biologically
      active substances that are involved in several physiological processes but also
      in pathological conditions such as inflammation. Since ten years now, it is well
      known that this enzyme exists under two forms: a constitutive (COX-1) and an
      inducible form (COX-2). Both enzymes are sensitive to inhibition by conventional
      nonsteroidal anti-inflammatory drugs (NSAIDs). Observations that COX-1, involved
      in several homeostatic processes, played a housekeeping role while COX-2
      expression was associated with inflammation and other pathologies such as cancer
      proliferation have led to the development of COX-2 selective inhibitors in order
      to reduce the classical side-effects, of which gastric irritation is the most
      common, associated with the use of conventional NSAIDs.

PMID- 10911018
TI  - The GABA transporter and its inhibitors.
AB  - GABA is the major inhibitory neurotransmitter in the brain and GABA re- uptake
      from the synaptic cleft is one important mechanism in the regulation of GABA
      activity. Inhibition of the re-uptake of GABA by potent and selective inhibitors
      of the GABA transporter enhances GABA activity. This property can be used
      therapeutically in for instance epilepsy or psychiatric disorders. In this paper
      putative structures of the GABA transporter, its mechanism of action, the
      progress made in the search for its amino acids involved in the binding of
      substrates and the SAR of inhibitors acting at the transporter will be discussed.
      To date only highly selective GAT-1 inhibitors are available. These compounds are
      lipophilic derivatives of (R)-nipecotic acid and guvacine. The most potent
      inhibitors of the cloned human GAT-1 are NNC-711 (IC50 = 0.04 mM) and tiagabine
      (IC50 = 0.07 mM). A diheteroarylvinyloxy analogue of tiagabine, 5 times more
      potent than tiagabine, has been reported recently. For the GAT-2, GAT-3 and BGT-1
      subtypes only compounds with a small preference for one of the subtypes have been
      published.

PMID- 10911020
TI  - Towards 3D structures of G protein-coupled receptors: a multidisciplinary
      approach.
AB  - Current strategies in pharmaceutical research comprise two methodologically
      different but complementary approaches for lead finding purposes, namely the
      random screening of compound libraries and the structure-based effort, commonly
      termed rational drug design. The structure-based approach is aimed to exploit 3D
      structure data of the molecular components involved in the molecular recognition
      event that underlies the attempt to therapeutically modulate the biological
      function of a macromolecular target with proven pathophysiological relevance for
      a disease state. In this context, G protein-coupled receptors (GPCRs) constitute
      the most prominent family of validated drug targets within biomedical research,
      since approximately 60 % of approved drugs elicit their therapeutic effects by
      selectively addressing members of that target family. From a 3D structure point
      of view, these transmembrane signal transduction systems represent the most
      challenging task for structure determination, which is due to the heterogeneous
      and fine-balanced environment conditions that are necessary for structural and
      functional integrity of the receptor protein. This contribution will address the
      different concepts to derive structurally relevant information on the
      transmemebrane seven-helix protein (7TM) domain of GPCRs with special emphasis
      laid on the multidisciplinarity of the applied methodologies. The current status
      of electron-cryo-microscopy on 2D crystals and even high-resolution x-ray
      crystallography on 7TM proteins will be introduced highlighting the
      transferability of the emerging structural principles onto the GPCR superfamily.
      Special techniques from bioinformatics and homology-related molecular modeling in
      combination with tailor-made protein simulation methodologies complement the
      experimentally derived data, in that they facilitate the 3D structure generation
      and structure validation process. This contribution summarises the most recent
      results of GPCR structure studies with the aim to underline the impact of
      structure data not only for the purpose of rationalising structure-activity data
      on low-molecular weight antagonists within the context of a protein binding
      pocket, but also for a better understanding of e.g. mutagenesis experiments, thus
      qualifying GPCR structure models as valid communication platforms establishing a
      functional link between molecular biology, biophysics, bioinformatics and organic
      chemistry in a highly efficient manner.

PMID- 10911019
TI  - Recent advances in the design and synthesis of SH2 inhibitors of Src, Grb2 and
      ZAP-70.
AB  - A perspective is offered on the recent development of Src-homology 2 (SH2)
      antagonists of Src, Grb2 and ZAP-70. Inhibiting Src SH2 is believed to be a
      potentially attractive way of regulating bone resorption. Grb2 SH2 has been shown
      to be an important component of the mitogenic ras pathway; and thus might be of
      utility in cancer research. ZAP-70 is a tyrosine kinase that is expressed solely
      in T-cells and natural killer cells. Since inhibition of the tandem SH2 domains
      of ZAP-70 has been shown to block T-cell proliferation, antagonists for this
      particular protein could have implications in immune suppression. The emphasis of
      the article is placed on the structure-based design, synthesis and biological
      activity of a number of newly reported SH2 antagonists in each of the three
      areas.

PMID- 10911021
TI  - Molecular manipulation of G-protein-coupled receptors: a new avenue into drug
      discovery.
AB  - During the past 10 years or so, associated with the introduction of molecular
      biology techniques to G protein-coupled receptor (GPCR) research, outstanding
      progress has been made in understanding the mechanisms of action of these key
      proteins and their physiological functions. in-vivo manipulation of levels of
      GPCRs using transgenic and gene knock-out approaches have been particularly
      successful in assessing the roles of specific GPCRs in animal physiology. Drug
      discovery is aiming to produce highly specific compounds based on subtle
      definition of receptor subtypes which can best be studied using heterologous
      expression of wild type or mutated forms of cDNA or genes encoding these
      proteins. Furthermore, new therapeutic opportunities may be provided by
      investigation of orphan receptors, the natural ligands for which remain
      unidentified. Some human diseases have been shown to be associated with rare
      mutations of GPCRs and the possibility that widely distributed polymorphisms in
      GPCR genes may allow selective therapeutic strategies for population subgroups is
      driving the development of the science of pharmacogenetics.

PMID- 10911022
TI  - Characterisation of G-protein-coupled receptors by antibodies.
AB  - G-protein-coupled receptors constitute a superfamily of integral membrane
      proteins encompassing hundreds of receptors for all types of chemical messengers,
      as well as, for example, the key molecules of our light and smell sensory
      systems, bioactive amines, peptide hormones, neurotransmitters and even proteins.
      Because of their complicated organisation with the characteristic seven
      transmembrane segments (7 TM) it has yet been impossible to structurally
      characterise any G-protein coupled receptor by crystallography or magnetic
      resonance. However, a number of indirect methods to study the structure and
      ligand binding of these proteins have been developed. Various studies have shown
      that antibodies produced against G-protein-coupled receptors are valuable tools.
      In this review we focus on the use of anti-receptor antibodies for the
      characterisation of membranes, cells and tissue, for mapping of the binding site,
      for purification by immunoaffinity chromatography and for biochemical studies of
      G-protein-coupled receptors. As an example we describe the characterisation of
      the G-protein-coupled neuropeptide Y receptor subtypes.

PMID- 10911023
TI  - Signal transduction pathways of G protein-coupled receptors and their cross-talk
      with receptor tyrosine kinases: lessons from bradykinin signaling.
AB  - G protein-coupled receptors (GPCRs) represent a major class of drug targets.
      Recent investigation of GPCR signaling has revealed interesting novel features of
      their signal transduction pathways which may be of great relevance to drug
      application and the development of novel drugs. Firstly, a single class of GPCRs
      such as the bradykinin type 2 receptor (B2R) may couple to different classes of G
      proteins in a cell-specific and time-dependent manner, resulting in simultaneous
      or consecutive initiation of different signaling chains. Secondly, the different
      signaling pathways emanating from one or several GPCRs exhibit extensive cross
      talk, resulting in positive or negative signal modulation. Thirdly, GPCRs
      including B2R have the capacity for generation of mitogenic signals. GPCR-induced
      mitogenic signaling involves activation of the p44/p42 "mitogen activated protein
      kinases" (MAPK) and frequently "transactivation" of receptor tyrosine kinases
      (RTKs), an unrelated class of receptors for mitogenic polypeptides, via currently
      only partly understood pathways. Cytoplasmic tyrosine kinases and protein
      tyrosine phosphatases (PTPs) which regulate RTK signaling are likely mediators of
      RTK transactivation in response to GPCRs. Finally, GPCR signaling is the subject
      of regulation by RTKs and other tyrosine kinases, including tyrosine
      phosphorylation of GPCRs itself, of G proteins, and of downstream molecules such
      as members of the protein kinase C family. In conclusion, known agonists of GPCRs
      are likely to have unexpected effects on RTK pathways and activators of signal
      mediating enzymes previously thought to be exclusively linked to RTK activity
      such as tyrosine kinases or PTPs may be of much interest for modulating GPCR
      mediated biological responses.

PMID- 10911024
TI  - Conformational and topographical considerations in designing agonist
      peptidomimetics from peptide leads.
AB  - The design of peptidomimetic ligands with agonist biological activities in vitro
      and in vivo has been challenging. Lofty goals have been set for this research
      including high potency, high receptor type selectivity, high stability in vitro
      and in vivo, and high efficacy in vitro and in vivo for agonists. A systematic
      stepwise strategy has been developed to accomplish these goals. These include
      determining the primary amino acid side chain residues required for molecular
      recognition and, in the case of agonist activity, those required for information
      transduction. In addition to determining the preferred backbone conformation
      which can serve as a template for the bioactive conformation (an alpha-helix,
      beta-turn, beta-sheet, etc.), a strategy has been developed to examine and
      determine the preferred side chain conformations in chi space (chi1, chi2, etc.).
      These include specific covalent and non-covalent constraints which can place the
      constrained side chains at highly preferred gauche (-), or gauche (+), or trans
      conformations. Examples are provided that illustrate this methodology and provide
      insight into the topographical requirements for ligand receptor interactions.
      Often, at this juncture one can obtain a quite precise 3D pharmacophore for the
      ligand, as well as high stability to agonist biodegradation and good
      bioavailability including the ability to cross membrane barriers. If a non
      peptide ligand is desired, efforts are in progress to develop templates, and
      aspects of conformational design that permit assembling of all components
      necessary for molecular recognition and transduction. Here the proper choice of
      template that can place the key side chain residue in 3D space is still
      difficult, and thus only partial success has been achieved in terms of potent and
      selective ligands. A few of these approaches are presented and discussed in some
      detail.

PMID- 10911025
TI  - Receptor targeting for tumor localisation and therapy with radiopeptides.
AB  - Receptor targeting with radiolabeled peptides has become very important in
      nuclear oncology in the past few years. The most frequently used peptides in the
      clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain
      chelators for the radioisotopes 111In, 86Y, 90Y, 67Ga, 68Ga and 64Cu or for 99mTc
      and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs
      of &alpha-melanocyte-stimulating hormone (&alpha-MSH), neurotensin, vasoactive
      intestinal peptide (VIP), bombesin (BN), substance P (SP) and
      gastrin/cholecystokinin (CCK) are also being developed, evaluated in vitro and in
      vivo and tested for clinical application. This review focuses on the expression
      in tumors and the regulation of receptors for these neuropeptides as well as the
      development of novel chelator-peptide conjugates suitable for in vivo
      scintigraphy or internal radiotherapy. The state of the art of radiopeptide
      pharmaceuticals is illustrated with four SRIF analogs, modified with the
      macrocyclic chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic
      acid (DOTA): [D-Phe1]-octreotide (DOTAOC), [D-Phe1, Tyr3]-octreotide (DOTATOC),
      vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal
      chelator capable of strongly encapsulating hard metals such as 111In and 67Ga for
      Single Photon Emission Tomography (SPET), 68Ga, 86Y and 64Cu for Positron
      Emission Tomography (PET) as well as 90Y for receptor-mediated radionuclide
      therapy and radiolanthanides which exhibit different interesting decay schemes.
      From biodistribution studies in experimental animals and from clinical data it is
      concluded that DOTATOC is currently the most suitable SRIF radiopeptide with the
      best potential in the clinic.

PMID- 10911358
TI  - Angiopoietin 2 expression in the retina: upregulation during physiologic and
      pathologic neovascularization.
AB  - Vascular development in the embryo requires coordinated signaling through several
      endothelial cell-specific receptors; however, it is not known whether this is
      also required later during retinal vascular development or as part of retinal
      neovascularization in adults. The Tie2 receptor has been implicated in
      stabilization and maturation of vessels through action of an agonist ligand,
      angiopoietin 1 (Ang1) and an antagonistic ligand, Ang2. In this study, we have
      demonstrated that ang2 mRNA levels are increased in the retina during development
      of the deep retinal capillaries by angiogenesis and during pathologic
      angiogenesis in a model of ischemic retinopathy. Mice with hemizygous disruption
      of the ang2 gene by insertion of a promoterless beta-galactosidase (beta gal)
      gene behind the ang2 promoter, show constitutive beta gal staining primarily in
      cells along the outer border of the inner nuclear layer identified as horizontal
      cells by colocalization of calbindin. During development of the deep capillary
      bed or retinal neovascularization, other cells in the inner nuclear layer and
      ganglion cell layer, in regions of neovascularization, stain for beta gal. Thus,
      there is temporal and spatial correlation of Ang2 expression with developmental
      and pathologic angiogenesis in the retina, suggesting that it may play a role.

PMID- 10911359
TI  - Compartmentalization of ceramide signaling: physical foundations and biological
      effects.

PMID- 10911360
TI  - Retinal and choroidal neovascularization.
AB  - The unique vascular supply of the retina, the ability to visualize the
      vasculature in vivo, and the ability to selectively express genes in the retina
      make the retina an ideal model system to study molecular mechanisms of
      angiogenesis. In addition, this area of investigation has great clinical
      significance, because retinal and choroidal neovascularization are the most
      common causes of severe visual loss in developed countries and new treatments are
      needed. As a result, interest in ocular neovascularization is rapidly growing and
      there has been considerable recent progress. Use of genetically engineered mice
      in recently developed murine models provides a means to investigate the role of
      individual gene products in neovascularization in two distinct vascular beds, the
      retinal vasculature and the choroidal vasculature. It appears that angiogenesis
      in different vascular beds has common themes, but also has tissue-specific
      aspects. This review summarizes recent progress in the field of ocular
      neovascularization and the prospects that it provides for the development of new
      treatments.

PMID- 10911361
TI  - Transcriptional silencing in fission yeast.
AB  - In eukaryotes, epigenetic events govern diverse processes, ranging from gene
      expression to other aspects of global chromosome architecture essential for
      preserving the integrity of the genome. Transcriptional silencing at the mating
      type locus, centromeres, and telomeres of the fission yeast is regulated by
      epigenetic mechanisms. Epigenetic states are inherited in cis during mitosis and,
      remarkably, even through meiosis. Several trans-acting genes that affect
      silencing are found to encode either chromatin proteins such as chromodomain
      proteins Swi6 and Clr4 or the factors that affect chromatin assembly, including
      histone deacetylase homologs Clr3 and Clr6. A recent study showed that Swi6 is
      involved in imprinting at the mating-type locus and contributes to the cellular
      memory responsible for maintenance of the silenced state. The "gene" in this
      instance thus comprises DNA plus the associated Swi6-containing protein complex.

PMID- 10911362
TI  - Human marrow stromal precursors are alpha 1 integrin subunit-positive.
AB  - In this work we studied the expression of adhesion molecules on primate human and
      non-human marrow stromal cells (primary cultures and lines) and on human CD34(+)
      hematopoietic normal and leukemic precursors. Differential expression of alpha1
      integrin subunit was observed, since this molecule was intensely expressed by
      marrow stroma but not detected on CD34(+) cells. We used this difference to
      select, in fresh bone marrow samples, alpha 1-positive cells. We found that all
      stromal precursors giving rise to colony-forming units-fibroblasts (CFU-F) were
      present in the alpha 1-positive fraction. No colonies were detected in the alpha
      1-negative fraction even after 2 weeks of culture. Phenotypic studies of stromal
      cells derived from alpha1-positive cells and grown in long-term marrow culture
      indicated that these cells were similar to stromal cells from primary cultures.
      We also observed early upregulation of alpha 4 and alpha 2 integrin subunits in
      cultures derived from alpha1-positive cells with maximal expression by day 10 (26
      and 51%, respectively) preceding a gradual decline to low to nil values at day 30
      (4.5 and 12%). These data indicate that alpha 1 integrin subunit is a marker for
      both mature stromal cells and stromal precursors, while alpha 2 and alpha 4
      integrin subunits are expressed primarily by immature cells.

PMID- 10911363
TI  - Platelet-derived growth factor induces collagenase 3 transcription in osteoblasts
      through the activator protein 1 complex.
AB  - Platelet-derived growth factor (PDGF) BB is a mitogen that stimulates bone
      resorption and increases collagenase 3 transcription in osteoblasts, although the
      mechanisms involved are as yet unknown. We examined the effect of PDGF BB on
      collagenase 3 transcription in cultures of osteoblasts from fetal rat calvariae
      (Ob cells). PDGF BB increased the activity of collagenase 3 promoter fragments
      transiently transfected into Ob cells. Deletion analysis of the collagenase
      promoter revealed three regions that impaired the induction of collagenase 3 by
      PDGF BB. A construct spanning base pair -53 to +28 collagenase 3 sequences, in
      relation to the start site of transcription +1, was fully responsive to PDGF BB
      and was studied in detail. Targeted mutations of an AP-1 site in this fragment
      decreased basal collagenase promoter activity and the responsiveness to PDGF BB,
      whereas mutations of Stat3 and Ets binding sites did not alter the response to
      PDGF. Electrophoretic mobility shift assay, using nuclear extracts from control
      and treated cells, revealed AP-1 nuclear protein complexes that were enhanced in
      extracts from PDGF BB-treated Ob cells. Supershift assays revealed that
      antibodies to c-Fos, Fos B, Fra-2, c-Jun, Jun B, and Jun D shifted the binding of
      nuclear extracts from cells treated with PDGF BB to AP-1 sequences. In
      conclusion, PDGF BB induces collagenase 3 transcription in osteoblasts by
      regulating nuclear proteins interacting with AP-1 sequences.

PMID- 10911364
TI  - Activation of osteoclasts by interleukin-1: divergent responsiveness in
      osteoclasts formed in vivo and in vitro.
AB  - Recently, it has been found that osteoclasts are induced and activated by
      osteoblastic cells through expression of receptor activator NF-kB ligand (RANKL),
      and that soluble recombinant RANKL, with M-CSF, can replace the need for
      osteoblastic cells in osteoclast formation. We exploited this opportunity to
      compare the responsiveness of osteoclast-like cells (OCL) formed in vitro in the
      absence of osteoblasts, with that of osteoclasts ex vivo. We found that while OCL
      responded to several hormones and cytokines like ex vivo osteoclasts, their
      responsiveness to interleukin-1 (IL-1) was fundamentally different: IL1 directly
      stimulated actin ring formation in OCL, but had no effect on actin rings or
      survival in osteoclasts ex vivo unless osteoblastic cells were present. This
      difference could not be attributed to the use of plastic culture substrates for
      OCL formation, nor to osteoblastic contamination, and did not seem to be mediated
      by the macrophages that form in OCL cultures. To understand the mechanisms by
      which IL-1 induces bone loss, it will need to be determined whether or not IL-1
      responsive OCLs have a counterpart in vivo. Whichever is the case, our data
      suggest that the behavior of osteoclasts formed in culture will not always
      predict that of osteoclasts in vivo.

PMID- 10911365
TI  - Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene.
AB  - The runt related transcription factor CBFA1 (AML3/PEBP2alphaA/RUNX2) regulates
      expression of several bone- and cartilage-related genes and is required for bone
      formation in vivo. The gene regulatory mechanisms that control activation and
      repression of CBFA1 gene transcription during osteoblast differentiation and
      skeletal development are essential for proper execution of the osteogenic
      program. We have therefore defined functional contributions of 5' regulatory
      sequences conserved in rat, mouse and human CBFA1 genes to transcription.
      Deletion analysis reveals that 0.6 kB of the bone-related rat or mouse CBFA1
      promoter (P1, MASNS protein isoform) is sufficient to confer transcriptional
      activation, and that there are multiple promoter domains which positively and
      negatively regulate transcription. Progressive deletion of promoter segments
      between nt -351 and -92 causes a striking 30- to 100-fold combined decrease in
      promoter activity. Additionally, 5' UTR sequences repress reporter gene
      transcription 2- to 3-fold. Our data demonstrate that CBFA1 is a principal DNA
      binding protein interacting with the 5' region of the CBFA1 gene in osseous
      cells, that there are at least three CBFA1 recognition motifs in the rat CBFA1
      promoter, and that there are three tandemly repeated CBFA1 sites within the 5'
      UTR. We find that forced expression of CBFA1 protein downregulates CBFA1 promoter
      activity and that a single CBFA1 site is sufficient for transcriptional
      autosuppression. Thus, our data indicate that the CBFA1 gene is autoregulated in
      part by negative feedback on its own promoter to stringently control CBFA1 gene
      expression and function during bone formation.

PMID- 10911366
TI  - Effect of cytokines on the proliferation/differentiation of stroma-initiating
      cells.
AB  - A culture system that identifies the precursor of murine bone marrow fibroblastic
      stromal cells (stroma-initiating cells, SIC) has been developed. In this system,
      mature fibroblasts are depleted by adherence to plastic dishes and the
      nonadherent cells are seeded at a low density, which results in the formation of
      colonies composed of fibroblastic cells. Macrophage colony-stimulating factor (M
      CSF) has been shown to accelerate the colony formation in the system. In this
      study, we examined the stroma-inducing activity of a number of cytokines. Neither
      granulocyte-CSF, stem cell factor, interleukin (IL)-1, IL-6, transforming growth
      factor, epidermal growth factor, insulin-like growth factor, platelet-derived
      growth factor, nor fibroblast growth factor showed the activity. Similarly, tumor
      necrosis factor (TNF) did not show any stroma-inducing activity, but the factor
      inhibited the stromal colony formation induced by M-CSF. In this study, we found
      that granulocyte/macrophage-CSF (GM-CSF) and IL-3, as well as M-CSF had the
      stroma-inducing activity. Neither an additive nor synergistic effect was observed
      when the three factors were assayed in various combinations. The stroma-inducing
      activity of M-CSF, GM-CSF and IL-3 was observed even if lineage-negative bone
      marrow cells were used as target cells, suggesting that mature hematopoietic
      cells such as macrophages and granulocytes were not involved in the induction of
      stromal colony formation by these factors. Our results raise the possibility that
      GM-CSF and IL-3 as well as M-CSF stimulate the proliferation or differentiation
      of the precursor of bone marrow fibroblastic stromal cells.

PMID- 10911367
TI  - Myostatin regulation during skeletal muscle regeneration.
AB  - Myostatin, a member of the TGF-beta superfamily, is a key negative regulator of
      skeletal muscle growth. The role of myostatin during skeletal muscle regeneration
      has not previously been reported. In the present studies, normal Sprague-Dawley
      and growth hormone (GH)-deficient (dw/dw) rats were administered the myotoxin,
      notexin, in the right M. biceps femoris on day 0. The dw/dw rats then received
      either saline or human-N-methionyl GH (200microg/100g body weight/day) during the
      ensuing regeneration. Normal and dw/dw M. biceps femoris were dissected on days
      1, 2, 3, 5, 9 and 13, formalin-fixed, then immunostained for myostatin protein.
      Immunostaining for myostatin revealed high levels of protein within necrotic
      fibres and connective tissue of normal and dw/dw damaged muscles. Regenerating
      myotubes contained no myostatin at the time of fusion (peak fusion on day 5), and
      only low levels of myostatin were observed during subsequent myotube enlargement.
      Fibres which survived assault by notexin (survivor fibres) contained moderate to
      high myostatin immunostaining initially. The levels in both normal and dw/dw rat
      survivor fibres decreased on days 2-3, then increased on days 9-13. In dw/dw
      rats, there was no observed effect of GH administration on the levels of
      myostatin protein in damaged muscle. The low level of myostatin observed in
      regenerating myotubes in these studies suggests a negative regulatory role for
      myostatin in muscle regeneration.

PMID- 10911368
TI  - Contrasting effects of oncogene expression on two carrier-mediated systems
      internalizing folate compounds in Fisher rat 3T3 cells.
AB  - Folate compound transport into Fisher rat 3T3 (FR3T3) cells at physiological pH
      occurs predominantly by an acid pH-dependent, mobile carrier system. However,
      influx of [(3)H]MTX by this system is 3-4-fold higher at pH 6 than at pH 7.5, the
      optimum for RFC-1-mediated folate compound transport. This acid pH dependency
      reflects an alteration of influx V(max) rather than of influx K(m) in these cells
      at different pH. Acid pH-dependent folate compound transport interacts
      effectively with MTX, 5lLCHO-folateH(4), 5lLCH(3)-folateH(4) and folic acid as
      permeants (influx Ki = 2.7-5.3 microM). The relative inhibition of influx of
      [(3)H]MTX by the organic anions, probenecid, and PO(4) was different than for RFC
      1 mediated influx. The folate requirements for growth in culture of FR3T3 cells
      and cytotoxicity of MTX compared to L1210 cells reflects the interactions of
      these folate compounds with acid pH-dependent folate transport. 5lLCHO-folateH(4)
      and PO(4) act as exchange anions for this system but their transpositioning has
      variable effects on transport. 5lLCHO-folateH(4) inhibits influx (decelerative
      equilibrium exchange) but stimulates efflux of [(3)H]MTX (accelerative
      equilibrium exchange) while PO(4) inhibits efflux. In FR3T3 cells transfected
      with cmyc and Hras, influx V(max) for [(3)H]MTX is downregulated 4-fold and 9
      fold, respectively. At the same time, RFC-1 expression, which is detectable in
      FR3T3 cells at the level of its mRNA and RFC-1 mediated folate compound
      transport, is increased 3-5-fold in these transfectants. The increase in RFC-1
      expression in FR3T3Hras cells appears to result from a higher rate of
      transcription of the gene in these cells as determined by a luciferase reporter
      gene assay of RFC-1 promoter activity. This downregulation of the acid pH
      dependent system and concomitant upregulation of the RFC-1 mediated system
      markedly altered pH dependency for influx of [(3)H]MTX in these transfectants
      compared to that seen in untransfected cells. We conclude that the major route
      for internalization at a physiological pH of folate compounds in FR3T3 cells is
      by an acid pH-dependent carrier-mediated system independent of RFC-1 expression
      and is downregulated by oncogene expression.

PMID- 10911370
TI  - Branched-chain amino acids inhibit proteolysis in rat skeletal muscle: mechanisms
      involved.
AB  - Incubation of isolated rat soleus and EDL muscles in the presence of 10 mM
      leucine resulted in a decreased proteolytic rate as measured by the release of
      tyrosine into the incubation medium. The effect of this branched-chain amino acid
      (BCAA) is associated with a decreased activity of the lysosomal proteases and a
      decreased expression of the genes of the ATP-ubiquitin-dependent proteolysis
      (ubiquitin and C8). Incubation of muscles in the presence of actinomycin D
      revealed that the effects of the amino acid can be accounted for by an inhibition
      of the transcription rate. The presence of leucine did not influence the gene
      expression of other nonlysosomal (m-calpain) and lysosomal (cathepsin B)
      proteolytic systems. It is concluded that the well-known effect of BCAA on muscle
      proteolysis is mediated, in the short term, by the inhibition of lysosomal
      proteolysis. In a longer period, based on the inhibition of gene transcription
      observed, an involvement of the ATP-dependent proteolytic system is also likely
      to occur.

PMID- 10911369
TI  - Synectin, syndecan-4 cytoplasmic domain binding PDZ protein, inhibits cell
      migration.
AB  - Syndecan-4, a member of the syndecan gene family of proteoglycans, is an
      important regulator of bFGF signaling. In particular, bFGF-dependent regulation
      of cell growth and migration has been linked to syndecan-4 cytoplasmic domain
      mediated interactions. Screening of a yeast two-hybrid library with a cytoplasmic
      domain of rat syndecan-4 identified a novel binding partner, here termed
      synectin. Synectin is highly homologous to semaphorin F binding protein semcap1,
      glucose 1 transporter binding protein glut1cbp, and RGS-GAIP/neuropilin-1 binding
      protein GIPC. Overexpression of synectin in ECV304 cells in culture led to a dose
      dependent inhibition of migration while not affecting cell adhesion or growth
      rate. We conclude that synectin is involved in syndecan-4-dependent interactions
      and may play a role in the assembly of syndecan-4 signaling complex.

PMID- 10911371
TI  - Calcium signaling induced by adhesion mediates protein tyrosine phosphorylation
      and is independent of pHi.
AB  - Our goal was to evaluate early signaling events that occur as epithelial cells
      make initial contact with a substrate and to correlate them with phosphorylation.
      The corneal epithelium was chosen to study signaling events that occur with
      adhesion because it represents a simple system in which the tissue adheres to a
      basal lamina, is avascular, and is bathed by a tear film in which changes in the
      local environment are hypothesized to alter signaling. To perform these
      experiments we developed a novel adhesion assay to capture the changes in
      intracellular Ca(2+) and pH that occur as a cell makes its initial contact with a
      substrate. The first transient cytosolic Ca(2+) peak was detected only as the
      cell made contact with the substrate and was demonstrated using fluorimetric
      assays combined with live cell imaging. We demonstrated that this transient
      Ca(2+) peak always preceded a cytoplasmic alkalization. When the intracellular
      environment was modified, the initial response was altered. Pretreatment with 1,2
      bis(o-aminophenoxy)ethane-N,N, N'N'-tetraacetic acid (BAPTA), an intracellular
      chelator, inhibited Ca(2+) mobilization, whereas benzamil altered the duration of
      the oscillations. Thapsigargin caused an initial Ca(2+) release followed by a
      long attenuated response. An inositol triphosphate analog induced a large initial
      response, whereas heparin inhibited Ca(2+) oscillations. Inhibitors of tyrosine
      phosphorylation did not alter the initial mobilization of cytosolic Ca(2) but
      clearance of cytosolic Ca(2+) was inhibited. Exposing corneal epithelial cells to
      BAPTA, benzamil, or thapsigargin also attenuated the phosphorylation of the focal
      adhesion protein paxillin. However, although heparin inhibited Ca(2+)
      oscillations, it did not alter phosphorylation of paxillin. These studies
      demonstrate that the initial contact that a cell makes with a substrate modulates
      the intracellular environment, and that changes in Ca(2+) mobilization can alter
      later signaling events such as the phosphorylation of specific adhesion proteins.
      These findings may have implications for wound repair and development.

PMID- 10911372
TI  - Cyclosporine has a direct effect on the differentiation of a mucin-secreting cell
      line.
AB  - Cyclosporine is a potent immunosuppressant used in the treatment of ulcerative
      colitis and keratoconjunctivitis sicca. Neither the etiologies of these diseases
      nor the mechanism by which cyclosporine exerts its therapeutic effect is well
      understood. Since both diseases are linked by a common decrease in mucin-filled
      goblet cells, this study tests a hypothesis that cyclosporine acts directly on
      goblet cells to promote their differentiation and production of secretory mucins.
      The HT29-18N2 human colon adenocarcinoma cell line, which is capable of forming
      monolayers of well-differentiated goblet cells, was used as a model system.
      Cyclosporine induced a dose-dependent increase in intracellular mucin stores. A 2
      week exposure to 1 microM cyclosporine resulted in an average increase in mucin
      volume of 94%. This increase resulted from both a higher percentage of cells with
      mucin stores and an increased volume of mucin per cell. PSC-833, a
      nonimmunosuppressive analog of cyclosporine, also increased mucin production. The
      intracellular accumulation of mucin was not a result of reduced secretion, since
      the time required for the release of pulse-radiolabeled glycoproteins was similar
      for both control and cyclosporine-treated monolayers. The effect of cyclosporine
      was not mediated by the drug's previously documented abilities to decrease
      cellular proliferation rates, inhibit calmodulin, antagonize prolactin receptor
      binding, or modulate prostaglandin production.

PMID- 10911373
TI  - Molecular mechanism of cGMP-mediated smooth muscle relaxation.
AB  - Contraction and relaxation of smooth muscle is a tightly regulated process
      involving numerous endogenous substances and their intracellular second
      messengers. We examine the key role of cyclic guanosine monophosphate (cGMP) in
      mediating smooth muscle relaxation. We briefly review the current art regarding
      cGMP generation and degradation, while focusing on the recent identification of
      the molecular mechanisms underlying cGMP-mediated smooth muscle relaxation. cGMP
      induced SM relaxation is mediated mainly by cGMP-dependent protein kinase
      activation. It involves several molecular events culminating in a reduction in
      intracellular Ca(2+) concentration and a decrease in the sensitivity of the
      contractile system to Ca(2+). We propose that the cGMP-induced decrease in Ca(2+)
      sensitivity is a strategic way to achieve "active relaxation" of the smooth
      muscle. In summary, we present compelling evidence supporting a key role for cGMP
      as a mediator of smooth muscle relaxation in physiological and pharmacological
      settings.

PMID- 10911374
TI  - Evaluation of human herpesvirus type 8 infection in childhood langerhans cell
      histiocytosis.
AB  - The etiology of Langerhans cell histiocytosis (LCH) is unknown. Viral causes,
      including human herpesvirus type 6 (HHV6), have been suggested but remain
      unproved. The recently discovered human herpesvirus type 8 (HHV8), the cause of
      Kaposi's sarcoma, infects dendritic cells in the bone marrow associated with
      multiple myeloma. Evidence for an association of HHV8 infection with LCH in
      children was studied by two approaches: indirectly by HHV8-specific serologic
      assays and directly by detection of HHV8 sequences using polymerase chain
      reaction in affected bone marrow samples. Using three different assays specific
      for HHV8 antibodies, 3 of 10 (30%) children with LCH had detectable HHV8
      antibodies, which was not different from the prevalence of 5 of 30 (17%) in
      healthy controls of similar age (P = 0.65). Of bone marrow samples from three
      additional children with LCH, all had amplifiable DNA but were negative for HHV8
      sequences. These studies of a small number of patients do not demonstrate an
      increased prevalence of HHV8 infection in children with LCH, and they do not
      suggest a causal role for HHV8 in the etiology of LCH.

PMID- 10911375
TI  - Fibrinogen bellingham: a gamma-chain R275C substitution and a beta-promoter
      polymorphism in a thrombotic member of an asymptomatic family.
AB  - Congenital dysfibrinogenemia is a rare cause of unexplained thrombosis. However,
      most individuals with dysfibrinogenemia are asymptomatic, suggesting that co
      morbid factors contribute to thrombo-embolic events. The potential roles of
      additional genetic or acquired prothrombotic risk factors are poorly understood
      because detailed family studies are lacking. Herein, we describe a family whose
      propositus was a young Caucasian man with recurrent venous thrombo-emboli and
      dysfibrinogenemia due to heterozygosity for an Arg-->Cys substitution at residue
      275 in the gamma-chain. The only additional thrombophilic abnormality found in
      the proband was heterozygosity for a G/A transition at position -455 in the
      fibrinogen beta-chain promoter; a genotype associated with high acute phase
      levels of fibrinogen. The proband's father, who died of a cerebral artery
      thrombosis, carried the gammaR275C substitution but not the beta-promoter -455
      variant. Among 14 living relatives, eight were heterozygous for one or the other
      mutation and only one, a 21-year-old niece, was dually affected. None had
      suffered bleeding or thrombosis. In vitro studies of the proband's purified
      fibrinogen revealed markedly abnormal thrombin-catalyzed polymerization and
      delayed fibrin clot lysis by tPA-activated plasmin. We hypothesize that the
      gammaR275C substitution predisposes to thrombosis by generating clots that are
      relatively resistant to fibrinolysis. The clinical risk is low, however, in the
      absence of an additional thrombophilic mutation. The beta-promoter variant could,
      theoretically, contribute to this risk by augmenting expression of the
      dysfibrinogen under conditions of stress. Like the common hereditary
      thrombophilias, heterozygous familial dysfibrinogenemia induces thrombosis in the
      setting of multiple prothrombotic influences.

PMID- 10911376
TI  - Platelet transfusions: utilization and associated costs in a tertiary care
      hospital.
AB  - We implemented a prospective study to evaluate platelet transfusion utilization,
      resource use, and costs in a tertiary care hospital over a 6-month period. All
      hospitalized patients receiving platelet transfusions between July and December
      1996 were followed prospectively to determine platelet use and costs. Clinical
      and financial data were collected, evaluated, and compared to identify trends in
      resource utilization based on admitting service and platelet-refractory status.
      One thousand nine hundred forty-four platelet units were transfused to 245
      hospitalized patients (50.6% male, mean age 49 years) during the study period.
      The majority of platelet units transfused were single donor (N = 1,460, 75%) and
      administered to bone marrow patients and patients with a hematological
      malignancy/disorder. Median hospitalization costs per admission were $27,750,
      ranging from a high of $58,729 for admission to the Bone Marrow Transplant
      service to $13,856 per admission to the Internal Medicine/Other service. Patients
      were refractory to platelet transfusions during 21.6% of hospitalizations.
      Hospital stays were longer (35.0 days vs. 14.4 days, P < 0.001) and inpatient
      hospital costs ($103,956 vs. $37,817, P < 0.001) were more than two and a half
      times higher for patients refractory to platelet transfusions. Platelet
      utilization, resource use, and costs vary by admitting service. Refractoriness to
      platelet transfusion was associated with significantly greater costs and lengths
      of stay. Monitoring platelet transfusion practices, particularly for patients
      refractory to platelet transfusions, may be beneficial for limiting costs and
      improving efficacy.

PMID- 10911377
TI  - Serum-soluble fas level determines clinical symptoms and outcome of patients with
      aggressive non-Hodgkin's lymphoma.
AB  - Soluble Fas (sFas) blocks apoptosis induced by Fas ligand in vitro. The serum
      concentration of sFas is elevated in lympho-proliferative diseases. We
      hypothesized that higher levels of sFas worsen the clinical symptoms and outcome
      of patients with aggressive non-Hodgkin's lymphoma (NHL). We prospectively
      measured the serum concentrations of sFas in 67 consecutive patients with
      aggressive NHL (59 with diffuse large cell lymphoma and 8 with diffuse small
      cleaved cell lymphoma). sFas was significantly elevated in patients with
      aggressive NHL compared to healthy controls (N = 36, P< 0.005), while sFas in
      patients with B symptoms (4.20 +/- 2.12 microg/l) was significantly higher than
      in those without B symptoms (2.66 +/- 1.08 microg/l, P < 0.005). No significant
      difference was observed between B-cell lymphoma and T-cell lymphoma or between
      patients with clinical stage I or II and those with clinical stage III or IV.
      Significant correlations were found between sFas concentration and both soluble
      interleukin-2 receptor (R = 0.400, P < 0.001) and C-reactive protein (R = 0.340,
      P < 0.01) levels in patients with aggressive NHL. No correlation was observed
      between sFas and either white blood cell count or lactate dehydrogenase.
      Generalized Wilcoxon analysis revealed that NHL patients with sFas less than 4
      microg/l had better overall survival than those with sFas above 4 microg/l (P <
      0.001). The serum concentration of sFas might be associated with clinical
      symptoms and the prognosis of patients with aggressive NHL.

PMID- 10911378
TI  - Alterations in hemostasis associated with hyperthermia in a canine model.
AB  - Use of hyperthermia in the treatment of cancer and viral infection has received
      renewed interest. However, the in vivo relationship between hyperthermia and
      direct versus indirect effects upon hemostasis are incompletely defined, although
      we do know that disseminated intravascular coagulation (DIC) is a common sequel
      to heat stroke. The purpose of the present study was to more precisely define the
      relationship between hyperthermia and derangements of hemostasis, thereby
      providing a guideline for the development of safe hyperthermia treatment
      regimens. The present investigation examined the in vivo effects of high-grade
      whole-body hyperthermia (WBH) (42.5 degrees C, 90 min) on hemostasis in a canine
      model. Induction of hyperthermia via extracorporeal circulation of heated blood
      (ECC-WBH) caused thrombocytopenia, increased plasma fibrin degradation products
      (FDPs), prolonged clotting times, increased serum liver enzymes, and evidence of
      spontaneous bleeding. However, when WBH was induced by peritoneal lavage (PL
      WBH), transient thrombocytopenia was the only significant alteration. Temporal
      correlation between hemostatic alterations and elevations in serum alanine
      aminotransferase (ALT) levels in the ECC-WBH treatment group suggested that liver
      injury is responsible, at least in part, for the coagulopathy associated with
      high-grade hyperthermia and that in the absence of liver injury, identical
      degrees of hyperthermia cause only incidental decreases in platelet numbers.

PMID- 10911379
TI  - Type I and type II T-cell profiles in aplastic anemia and refractory anemia.
AB  - Immune-mediated suppression of hematopoiesis has been considered the most
      important mechanism in the development of idiopathic aplastic anemia (AA) and
      some types of myelodysplastic syndrome (MDS). Using flow cytometric analysis of
      intracellular cytokine expression at the single-cell level, we analyzed helper-T
      (Th) and cytotoxic-T (Tc) subsets in patients with AA and MDS of refractory
      anemia (RA) subtype. The results showed marked increases in the Th1/Th2 ratio and
      Tc1/Tc2 ratio in both AA and MDS/RA. Overproduction of cytokines inhibitory to
      hematopoiesis reported so far might be a reflection of imbalanced development of
      Th and Tc. Determination of the factors that affect Th and Tc profiles may lead
      to further understanding of immunological states and the development of effective
      immunotherapy in AA as well as some types of MDS.

PMID- 10911380
TI  - Quantitative flow cytometry for the differential diagnosis of leukemic B-cell
      chronic lymphoproliferative disorders.
AB  - We have investigated whether the quantitative flow cytometry is an useful tool to
      better characterize B-cell chronic lymphoproliferative disorders (CLDs).
      Peripheral blood samples from 104 patients with leukemic B-cell disorders and 20
      healthy donors were analyzed. Directly phycoerythrin-conjugated CD19, CD20, CD22,
      CD23, CD79b, and CD5 monoclonal antibodies (MoAbs) and QuantiBRITE pre-calibrated
      beads were used to calculate the number of antigen molecules per cell, expressed
      as antibody binding capacity (ABC). As compared to normal controls, in chronic
      lymphocytic leukemias (CLL) all MoAbs tested, with the exception of CD23 and CD5,
      showed lower ABC levels. In prolymphocytic leukemias (PL), CD5 and CD23 antigens
      were constantly absent while lower CD19 and CD22 ABC levels were observed. Hairy
      cell leukemias (HCL) displayed very high levels of CD20 and CD22. Of interest,
      splenic lymphomas with villous lymphocytes (SLVL) could be discriminated from HCL
      for higher CD79b and lower CD19 ABC values. Finally, higher CD20 levels were
      detected in follicular lymphomas (FL), whereas higher CD79b and CD5 levels
      characterized mantle cell lymphomas (MCL). Seven out of 61 CLL cases were defined
      as morphologically atypical. When compared with typical forms, lower levels of
      CD19 and CD23 and higher CD20 and CD22 ABC values were detected. However, we
      failed to demonstrate quantitative differences between atypical CLL and MCL. Our
      results suggest that quantitative flow cytometry may be a useful additional tool
      to better identify some types of B-cell CLDs.

PMID- 10911381
TI  - Increased D-dimer levels correlate with binding of activated protein C, but not
      tissue factor expression, on peripheral blood monocytes in cancer patients.
AB  - Monocyte tissue factor expression is supposed to play an important role in the
      hypercoagulability of blood in cancer patients. The relation between coagulation
      parameters and the expression of monocyte membrane proteins involved in
      hemostasis or monocyte activation was studied in 21 patients with a disseminated
      malignancy and 21 age- and sex-matched healthy controls. In the cancer patient
      group no increase of monocyte tissue factor expression was found (8. 4% vs. 7.8%;
      P = 0.83), but a significant increase of monocyte-bound activated protein C (APC)
      (28.8% vs. 13.4%; P = 0.009) and monocyte CD16 expression (34.5% vs. 27.0%; P =
      0.007) was observed. There was also a significant increase of D-dimers (2.0 vs.
      0.2 microg/ml; P = 0.001), a decrease of antithrombin (83.5% vs. 102.0%; P =
      0.004), but no increase of TAT complexes (1.7 vs. 1.5 microg/l; P = 0.38) or
      factor VII(a) (68.5% vs. 75.0%; P = 0.52). The increase of D-dimers was
      significantly correlated with the monocyte APC (R = 0.60; P = 0. 005), but not
      with monocyte tissue factor levels (R = -0.22; P = 0. 35) or TAT complexes (R =
      0.12; P = 0.60). These results reflect a local rather than systemic thrombin and
      fibrin formation. It is suggested that the APC formed locally enters the
      circulation and binds to peripheral blood monocytes. APC bound on monocytes is
      known to inhibit monocyte cytokine production and might therefore be involved in
      regulatory responses of monocytes in cancer patients.

PMID- 10911382
TI  - Iron absorption and transport-an update.
AB  - Iron is vital for all living organisms. However, excess iron is hazardous because
      it produces free radical formation. Therefore, iron absorption is carefully
      regulated to maintain an equilibrium between absorption and body loss of iron. In
      countries where heme is a significant part of the diet, most body iron is derived
      from dietary heme iron because heme binds few of the luminal intestinal iron
      chelators that inhibit absorption of non-heme iron. Uptake of luminal heme into
      enterocytes occurs as a metalloporphyrin. Intracellularly, iron is released from
      heme by heme oxygenase so that iron leaves the enterocyte to enter the plasma as
      non-heme iron. Ferric iron is absorbed via a beta(3) integrin and mobilferrin
      (IMP) pathway that is not shared with other nutritional metals. Ferrous iron
      uptake is facilitated by DMT-1 (Nramp-2, DCT-1) in a pathway shared with
      manganese. Other proteins were recently described which are believed to play a
      role in iron absorption. SFT (Stimulator of Iron Transport) is postulated to
      facilitate both ferric and ferrous iron uptake, and Hephaestin is thought to be
      important in transfer of iron from enterocytes into the plasma. The iron
      concentration within enterocytes reflects the total body iron and either
      upregulates or satiates iron-binding sites on regulatory proteins. Enterocytes of
      hemochromatotics are iron-depleted similarly to the absorptive cells of iron
      deficient subjects. Iron depletion, hemolysis, and hypoxia each can stimulate
      iron absorption. In non-intestinal cells most iron uptake occurs via either the
      classical clathrin-coated pathway utilizing transferrin receptors or the poorly
      defined transferrin receptor independent pathway. Non-intestinal cells possess
      the IMP and DMT-1 pathways though their role in the absence of iron overload is
      unclear. This suggests that these pathways have intracellular functions in
      addition to facilitating iron uptake.

PMID- 10911383
TI  - Pulmonary hemorrhage in a hemophiliac simulating a lung neoplasm.
AB  - We report an elderly, male smoker with moderate hemophilia B who presented with
      hemoptysis. Chest imaging revealed a well-circumscribed, pulmonary, mass lesion.
      Repeated bronchoscopy failed to make a diagnosis, and the patient ultimately
      underwent open thoracotomy with resection of the mass. Pathologic examination
      revealed hemorrhagic changes in association with bullous lung disease. This is
      the first report of symptomatic pulmonary hemorrhage in a patient with hemophilia
      B. Hemorrhage into a pre-existing bulla can simulate a primary lung neoplasm.

PMID- 10911384
TI  - Rubella-associated aplastic anemia treated by syngeneic stem cell
      transplantations.
AB  - A 14-year-old boy presented with aplastic anemia 3 months after contracting
      rubella. Stem cell transplantations from his identical twin were carried out.
      Successful engraftment occurred only when conditioning therapy was given prior to
      the infusion of the syngeneic stem cells, supporting an immune mechanism to
      explain the pathogenesis of virus-associated aplastic anemia.

PMID- 10911385
TI  - Prolonged complete remission of myelodysplastic syndrome treated with danazol,
      retinoic acid and low-dose prednisone.
AB  - Myelodysplastic syndrome (MDS) is a diverse group of clonal hematologic
      neoplasms. Different medications have been tried in MDS; however, no effective
      treatment has been yet established. We report a patient with MDS who achieved a
      complete remission in response to combination therapy of danazol, retinoic acid,
      and prednisone. A 53-year-old female presented with pancytopenia, macrocytosis,
      and hypercellular bone marrow with erythroid hyperplasia and dysplasia and 10%
      ringed sideroblasts. Cytogenetic studies revealed the presence of two abnormal
      clones. She was diagnosed as having MDS-refractory anemia and was given blood
      transfusions to maintain blood cell counts at acceptable levels. At the same
      time, she was started on a combination of danazol (600 mg/day), retinoic acid
      (100 mg/day), and prednisone (10 mg every other day). Fourteen months later, the
      patient was in complete hematologic remission; she had normal peripheral blood
      count, and the blood smear showed normal morphology. Bone marrow studies revealed
      normal trilineage hematopoiesis. She was continued on the same combination
      treatment for 86 months, and she remained in complete clinical remission. Eighty
      eight months from diagnosis, she relapsed with acute myeloid leukemia. This is
      the first reported case of MDS-RA that sustained a complete hematologic remission
      for a prolonged period in response to this combination treatment. This report
      indicates that restoration of normal hematopoiesis, prolongation of disease-free
      survival, and delay in the transformation to acute leukemia may be achieved by
      this combination of treatment in a subset of patients with MDS, especially
      refractory anemia with severe thrombocytopenia.

PMID- 10911386
TI  - Multiple myeloma expressing CD19(+)CD56(-) phenotype.
AB  - A 70-year-old woman presented with monoclonal gammopathy, pancytopenia, and renal
      insufficiency, which were initially refractory to combination chemotherapy by
      VMMD (vincristine, ranimustine, melphalan, and dexamethasone) and MP (melphalan
      and prednisolone) regimens. The myeloma cells, which consisted of 73% of bone
      marrow nucleated cells, expressed CD38(+), CD19(+), CD56(-), CD45(-), CD49e(-),
      and MPC-1(+) phenotypes by flow cytometric analysis and showed the rearranged
      immunoglobulin heavy chain (IgH) gene by Southern blotting. By immunostaining,
      the myeloma cells were positive for cytoplasmic immunoglobulin light chain kappa.
      These results suggest that myeloma cells can express CD19(+)CD56(-), the
      phenotype considered to be expressed on only normal plasma cells.

PMID- 10911387
TI  - Congenital dyserythropoietic anemia type III associated with congenital
      atrioseptal defect has led to severe cardiac problems in a 32-year-old patient.
AB  - We report the case of a 32-year-old woman who was admitted at hospital because of
      ortho-dyspnea, arrhythmia, and paleness. Clinical examination showed continuous
      arrhythmia, systolic heart murmur, enlargement of spleen and liver, and
      pathologic hematological parameters, thus indicating an intravasal hemolysis
      (elevated HBDH, bilirubin, and reticulocytes; reduced hemoglobin and haptoglobin
      levels), and bone-marrow-smears showed a typical cytomorphology of CDA III. The
      patient's diagnosis was heart failure caused by mitral valve insufficiency due to
      congenital atrioseptal defect associated with congenital dyserythropoietic anemia
      type III (CDA III).

PMID- 10911388
TI  - Primary effusion lymphoma with B-cell phenotype.
AB  - We describe here a case of primary effusion lymphoma that occurred in a 78-year
      old woman. She was successively treated with prednisolone but died 15 months
      after the diagnosis of primary effusion lymphoma. The immunohistochemistry
      revealed the neoplastic cells to be CD19(+), CD20(+), CD21(+), Sm-Ig(+), and HLA
      DR(+). This patient exhibited clonal IgH and clonal kappa light chain gene
      rearrangement, indicating a B-cell origin. The present case was distinguished
      from the majority cases of HHV-8-positive primary effusion lymphoma. Here we
      present clinical details of response to therapy in this case.

PMID- 10911389
TI  - Tributyrin plus all-trans-retinoic acid efficiently induces fetal hemoglobin
      expression in human erythroleukemia cells.
AB  - Fourteen butyrate derivatives and retinoic acid were tested with respect to the
      hemoglobin F-inducing activity using the K562 erythroleukemia cell line as a
      model system. Four novel butyrate derivatives with hemoglobin F-inducing activity
      have been identified. Combined treatment with the butyrate derivative tributyrin
      and retinoic acid in vitro led to a 7-fold increase of hemoglobin synthesis.
      Tributyrin and retinoic acid might be promising drugs for clinical trials to
      treat patients with beta-hemoglobinopathies.

PMID- 10911390
TI  - Acquired inhibitor of thrombin associated with an ulcerative colitis.

PMID- 10911391
TI  - Factor XII deficiency associated with coronary stent thrombosis.

PMID- 10911392
TI  - Mutation analysis of the SPARC gene in the 5q-syndrome.

PMID- 10911394
TI  - Meiosis and apoptosis in germ cells of X-autosome translocation carrier boars.
AB  - Meiotic features and fate of germ cells were studied using electron microscopy on
      surface spread spermatocytes and in situ tests for apoptosis on testicular
      tissues of normal boars and X-autosome translocation (X-AT) carrier boars.
      Histological sections of the translocation t(Xp+; 14q-) carrier boars showed
      accumulation of degenerating germ cells including binucleate and multinucleate
      cells, as well as pyknosis and nuclear fragmentation characteristic of apoptosis.
      Synaptonemal complex analysis of X-AT carrier boars revealed 19 bivalents
      including a large complex made up of the altered X (Xp+) and normal chromosome
      14, and a smaller element representing the Y chromosome in synapsis with the
      derived chromosome 14 (14q-) in most (89.3%) of the germ cells. In situ tests for
      apoptotic DNA fragmentation revealed positive signals exclusively among early
      spermatocytes and degenerating germ cells. These findings and the absence of
      stages beyond pachytene suggest that the meiocytes are arrested at pachytene and
      eliminated through apoptotic process in spite of the complete synapsis displayed
      by the chromosomes involved in this translocation. Failure of meiotic progress in
      our X-AT carriers would appear to be the result of the disruption of gene
      sequence (or function) caused by the involvement of the X chromosome in this
      rearrangement, rather than the deleterious consequences of abnormal segregation
      anticipated in reciprocal translocation carriers. We hypothesize that this
      disruption could have affected the induction of stage-specific gene products in
      meiosis such as heat shock proteins and caused the excessive release of
      endonucleases normally produced by early prophase meiocytes, leading to their
      apoptosis in our X-autosome translocation carrier boars.

PMID- 10911393
TI  - Pattern of expression of the KGF receptor and its ligands KGF and FGF-10 during
      postnatal mouse mammary gland development.
AB  - The expression of the KGF receptor (KGFR) and its stromal ligands, KGF and FGF
      10, was compared during mouse mammary gland development. KGFR expression in
      mammary parenchyma is maximal in mature virgin mice, declines during pregnancy
      and lactation, but rises after weaning. The rise in KGFR mRNA in the virgin
      animal corresponds to parenchymal growth. The fall in KGFR expression in
      pregnancy is driven by hormone-induced alveolar differentiation since the level
      of KGFR mRNA is 5-fold higher in isolated ductal cells compared to alveolar
      cells. KGF and FGF-10 expression patterns differ during ductal development. FGF
      10 is also expressed at about a 15-fold higher molar level than KGF. During
      pregnancy and lactation, expression of KGF and FGF-10 decreases in intact fat
      pads but is unchanged in parenchyma-free fat pads. Thus, the decrease in KGF and
      FGF-10 expression observed in intact glands during pregnancy and lactation is not
      a direct consequence of the changing hormonal milieu but more likely reflects an
      increase in the ratio of epithelium to stroma. Differences in the level and
      pattern of expression of mRNA for KGF, FGF-10, and the KGFR during postnatal
      development of the mouse mammary gland are a result of morphological development,
      changes in the ratio of stroma to epithelium, and hormonal regulation of cell
      differentiation. These changes suggest that the biological roles that these
      growth factors play are regulated by fluctuations in both growth factor and
      growth factor receptor expression and that KGF and FGF-10 may have different
      regulatory functions.

PMID- 10911395
TI  - Genetic reprogramming of lactate dehydrogenase, citrate synthase, and
      phosphofructokinase mRNA in bovine nuclear transfer embryos produced using bovine
      fibroblast cell nuclei.
AB  - Adult animal cloning has progressed to allow the production of offspring cloned
      from adult cells, however many cloned calves die prenatally or shortly after
      birth. This study examined the expression of three important metabolic enzymes,
      lactate dehydrogenase (LDH), citrate synthase, and phosphofructokinase (PFK), to
      determine if their detection in nuclear transfer (NT) embryos mimics that
      determined for in vitro produced embryos. A day 40 nuclear transfer produced
      fetus derived from an adult cell line was collected and fetal fibroblast cultures
      were established and maintained. Reconstructed NT embryos were then produced from
      this cell line, and RT-PCR was used to evaluate mRNA reprogramming. All three
      mRNAs encoding these enzymes were detected in the regenerated fetal fibroblast
      cell line. Detection patterns were first determined for IVF produced embryos (1
      cell, 2-cell, 6-8 cell, morula, and blastocyst stages) to compare with their
      detection in NT embryos. PFK has three subunits: PFK-L, PFK-M, and PFK-P. PFK-L
      and PFK-P were not detected in bovine oocytes. PFK subunits were not detected in
      6-8 cell embryos but were detected in blastocysts. Results from NT embryo RT-PCR
      demonstrated that PFK was not detected in 8-cell NT embryos but was detected in
      NT blastocysts indicating that proper nuclear reprogramming had occurred. Citrate
      synthase was detected in oocytes and throughout development to the blastocyst
      stage in both bovine IVF and NT embryos. LDH-A and LDH-B were detected in bovine
      oocytes and in all stages of IVF and NT embryos examined up to the blastocyst
      stage. A third subunit, LDH-C was not detected at the blastocyst stage in IVF or
      NT embryos but was detected in all earlier stages and in mature oocytes. In
      addition, LDH-C mRNA was detected in gonad isolated from the NT and an in vivo
      produced control fetus. These results indicate that the three metabolic enzymes
      maintain normal expression patterns and therefore must be properly reprogrammed
      following nuclear transfer.

PMID- 10911397
TI  - Derivation and characterization of pluripotent embryonic germ cells in chicken.
AB  - Embryonic germ (EG) cell lines established from primordial germ cells (PGCs) are
      undifferentiated and pluripotent stem cells. To date, EG cells with proven germ
      line transmission have been completely established only in the mouse with
      embryonic stem (ES) cells. We isolated PGCs from 5.5-day-old (stage 28) chicken
      embryonic gonads and established a putative chicken EG cell line with EG culture
      medium supplemented with stem cell factor (SCF), leukemia inhibitory factor
      (LIF), basic fibroblast growth factor (bFGF), interleukin-11 (IL-11), and insulin
      like growth factor-I (IGF-I). These cells grew continuously for ten passages (4
      months) on a feeder layer of mitotically active chicken embryonic fibroblasts.
      After several passages, these cells were characterized by screening with the
      periodic acid-Schiff reaction, anti-SSEA-1 antibody, and a proliferation assay.
      The chicken EG cells maintained characteristics of gonadal PGCs and
      undifferentiated stem cells. When cultured in suspension, the chicken EG cells
      successfully formed an embryoid body and differentiated into a variety of cell
      types. The chicken EG cells were injected into stage X blastodermal layer and
      produced chimeric chickens with various differentiated tissues derived from the
      EG cells. Chicken EG cells will be useful for the production of transgenic
      chickens and for studies of germ cell differentiation and genomic imprinting.

PMID- 10911396
TI  - Porcine leptin receptor: molecular structure and expression in the ovary.
AB  - The porcine leptin receptor complementary DNA was cloned and sequenced and the
      leptin receptor gene expression evaluated in the porcine ovary. An open reading
      frame of 3498 nt cDNA was amplified from pig liver mRNA by RT-PCR. Sequence
      homology with the extracellular, transmembrane, and cytoplasmic domains of human,
      mouse, rat, sheep, and cow leptin receptors varied between 45% and 90%. Leptin
      receptor mRNA was present in porcine kidney, liver, spleen, lung, brain, testis,
      uterus, ovary, corpus luteum (CL), theca, and granulosa cells. The abundance of
      leptin receptor transcripts and protein varied during luteinization of granulosa
      cells in vitro and in the CL during the pig luteal phase. In the postovulatory
      CL, both mRNA and protein were low but detectable, maximal expression was
      observed in the midcycle CL, and lowest abundance occurred in regressed CL.
      Leptin receptor mRNA was present in granulosa cells at isolation and increased in
      abundance as the cells luteinized over 96 hr in culture. Leptin receptor protein
      was detectable after 12 hr of in vitro luteinization. We conclude that leptin
      receptor is expressed in granulosa and luteal cells, and varies during pig
      ovarian cell differentiation.

PMID- 10911398
TI  - Effects of Kit Ligand and anti-Kit antibody on growth of cultured mouse preantral
      follicles.
AB  - Paracrine regulations between the oocyte and granulosa cells are likely to be key
      regulators of early folliculogenesis. Evidence obtained from genetic mutants as
      well as in vivo experiments suggest that Kit and Kit Ligand (KL) may regulate
      early follicular morphogenesis and function. In this study, we used in vitro
      culture of intact mouse follicles to confirm and extend these findings. Two
      concentrations of Kit Ligand (20 and 50 ng/ml) or an antibody blocking the Kit
      Kit Ligand interactions (SC1494) were added to preantral follicles grown
      individually for 12 days and which were finally triggered to ovulate. Effects on
      follicle and oocyte survival, granulosa cell function (antrum formation, cell
      numbers, steroidogenesis), and oocyte function (growth, survival, nuclear and/or
      cytoplasmic maturation) were then analyzed. In optimal culture conditions
      (presence of 5% fetal calf serum), 50 ng/ml of KL significantly improved
      cytoplasmic maturation of the oocyte and increased follicular testosterone
      output, but other parameters were not altered. In serum-free culture conditions,
      KL was mitogenic for granulosa cells at 50 ng/ml, but could not induce antrum
      formation and no differences were observed between control and treated groups for
      steroidogenesis or oocyte growth. Blockade of Kit-Kit Ligand interactions by
      addition of a blocking antibody decreased oocyte survival 6-9 days after addition
      of the antibody, but did not upset granulosa cell proliferation. Antrum formation
      was, however, strongly inhibited. In addition, the blocking antibody markedly
      reduced aromatase activity of granulosa cells. We conclude that Kit/KL
      interactions are important for antrum formation and follicular steroidogenesis
      and regulate survival and cytoplasmic maturation of the oocyte.

PMID- 10911399
TI  - Induction of gonadal intersex in genotypic male rainbow trout (Oncorhynchus
      mykiss) embryos following immersion in estradiol-17beta.
AB  - This investigation was conducted to determine the initial period of gonadal
      sensitivity to estrogen in genetically male rainbow trout (Oncorhynchus mykiss).
      Fish were immersed in approximately 250 microg estradiol-17beta, (E2)/l for two 2
      hr periods during different stages of embryonic development beginning 30 days
      postfertilization (DPF) and continuing until 68 DPF. Histological analysis of
      gonad samples indicated a significant proportion of E2-treated fish had intersex
      gonads; these gonads were primarily comprised of testicular tissue with one or
      more oocytes scattered throughout. The most sensitive period for altering normal
      testicular development was found to occur between 44 and 51 DPF (63% intersex),
      while the labile period in general was determined to span 24 days (from 30 to 54
      DPF). Additionally, quantitative RT-PCR was used to measure estrogen receptor
      (ER) mRNA expression in whole individual untreated embryos at six weekly time
      points throughout the period of E2-exposure. Although the intersex condition was
      not observed throughout the entire E2-exposure period, ER mRNA was detected at
      each time point assayed.

PMID- 10911400
TI  - Centrosome reduction during Rhesus spermiogenesis: gamma-tubulin, centrin, and
      centriole degeneration.
AB  - Centrosome reduction during spermiogenesis has been studied using anti-gamma
      tubulin and anti-centrin antibodies and electron microscopy in nonhuman primates.
      Rhesus spermatids possess apparently normal centrosomes comprising a pair of
      centrioles associated with gamma-tubulin and centrin. However, they do not
      nucleate detectable microtubules. The spermatids discard gamma-tubulin in the
      residual bodies during the spermiation stage. Mature sperm do not have any
      detectable gamma-tubulin. About half of the centrin associated with the distal
      centriole degenerates during spermiogenesis and the remainder is intimately bound
      to the centriolar microtubules. The mature sperm possess highly degenerated
      distal centrioles. The centriolar microtubules degenerate in the rostral region
      and the ventral side of the sperm. The study indicates that the centrosome is
      reduced during rhesus spermiogenesis, but not completely as in mice.

PMID- 10911401
TI  - Zinc is sufficiently abundant within mammalian sperm nuclei to bind
      stoichiometrically with protamine 2.
AB  - Although studies have demonstrated that zinc can bind to sperm nuclear proteins,
      specifically protamine 2, it has not been shown that the metal is sufficiently
      abundant inside the sperm nucleus to interact stoichiometrically with these
      proteins. In this study proton-induced X-ray emission (PIXE) has been used to
      measure the amount of sulfur and zinc within the nuclei of individual sperm cells
      to infer the stoichiometry of zinc binding to protamine 2 in six species of
      mammal: bull, chinchilla, stallion, hamster, human, and mouse (protamine 2
      comprises from 0% (bull) to 67% (mouse) of the protamine present in the sperm of
      these animals). Using the sulfur mass and electrophoretic data on the relative
      proportion of protamine 1 and protamine 2 in the sperm chromatin of these
      species, the protamine 1, protamine 2, and total protamine contents within each
      species sperm nuclei have been determined. The PIXE measurements reveal that the
      zinc content of the sperm nucleus varies proportionately with the protamine 2
      content of sperm chromatin. PIXE analyses of hamster protamines extracted under
      conditions that appear to at least partially preserve zinc binding also confirm
      that the majority of the metal is bound to protamine. In five of the species
      examined, sufficient zinc is present for each protamine 2 molecule to bind one
      zinc. The results obtained for chinchilla sperm, conversely, indicate the
      chinchilla protamine 2 molecule may interact differently with zinc. Chinchilla
      sperm only contain enough zinc for one atom to be bound to two protamine 2
      molecules.

PMID- 10911402
TI  - Excessive concentration of glucose during in vitro maturation impairs the
      developmental competence of bovine oocytes after in vitro fertilization:
      relevance to intracellular reactive oxygen species and glutathione contents.
AB  - The effect of glucose (0, 1.5, 5.6 or 20.0 mM) in synthetic oviduct fluid
      supplemented with 20 amino acids (SOFaa) on the developmental competence of
      bovine oocytes after in vitro fertilization was investigated. Intracellular
      reactive oxygen species (ROS) and the glutathione content of bovine oocytes
      matured in SOFaa containing 0-20.0 mM glucose were also examined. When oocytes
      were matured in SOFaa without glucose, the nuclear maturation rate was lower than
      that in oocytes matured in glucose-containing medium. The developmental
      competence to the blastocyst stage of oocytes matured in 1.5 mM glucose was
      higher than that of oocytes matured in 20.0 mM glucose. In addition, the
      intracellular ROS content of oocytes matured in 0, 1.5 or 5.6 mM glucose was
      lower than that of oocytes matured in 20.0 mM glucose. Furthermore, the
      intracellular glutathione content of oocytes matured in 0, 1.5 or 5.6 mM glucose
      was higher than that of oocytes matured in 20.0 mM glucose. These results show
      that excessive glucose in the medium for oocyte maturation impairs the
      development of bovine oocytes to the blastocyst stage, possibly due to the
      increase of ROS and the decrease in the intracellular glutathione content of
      bovine oocytes.

PMID- 10911403
TI  - Molecular and binding characteristics of IP3 receptors in bovine spermatozoa.
AB  - We have shown the presence of inositol 1,4,5-triphosphate (IP3) receptors in
      bovine spermatozoa. These receptors are mainly localized and functionally
      associated with the acrosome region. Molecular characterization of these bovine
      IP3 receptors has shown that the functional size of the IP3 binding domain is a
      protein of 66+/-2 kDa, in agreement with the size of both bovine adrenal cortex
      and bovine adrenal medullar chromaffin cells IP3 receptors. In contrast, bovine
      cerebellum IP3 receptor displays molecular weight of 220+/-5 kDa, a value in
      agreement with data in the literature. Bovine IP3 receptors have a one-affinity
      state characterized by a low affinity (Kd 750 nM) and a relatively high density
      (7.5 pmol/mg protein). They are functional and release internal calcium upon the
      binding of the second messenger. Moreover, the finding that the specific A1
      adenosine receptor agonist R-PIA elicits almost the same effect as IP3 might be
      of some help in understanding the physiological role of these inhibitory
      adenosine receptors in mammalian spermatozoa.

PMID- 10911404
TI  - Proteinases, cell cycle regulation, and apoptosis during mammary gland involution
      (minireview).

PMID- 10911405
TI  - Mechanism of the block to hybridization and selfing between the sympatric
      ascidians Ciona intestinalis and Ciona savignyi.

PMID- 10911406
TI  - Anti-goitrous effect of lecithin-bound iodine in propylthiouracil treated rats.
AB  - OBJECTIVE: Excess iodine and some iodine-containing compounds are known to affect
      various parameters of thyroid function. Lecithin-bound iodine (LBI) is a compound
      which induces involution of an enlarged thyroid. LBI was tested for its ability
      to affect thyroid ornithine decarboxylase (ODC) activity and apoptosis. METHODS:
      LBI was given orally to propylthiouracil-pretreated rats and the changes in ODC
      activity and apoptosis were observed. The thyroid apoptosis was detected by DNA
      laddering and flow cytometry. RESULTS: LBI suppressed the thyroid ODC activity
      within one hour after its administration and lowered slightly but significantly
      the thyroid putrescine levels at 3 h. The DNA cleavage ladder was evident at 3-6
      h after LBI treatment. Propylthiouracil induced thyroid enlargement was reduced
      significantly at 3 days after chronic treatment with LBI. The thyroidal content
      of putrescine was also decreased after chronic treatment. These effects of LBI
      were essentially the same as those of excess iodide, while other iodinated
      compounds including amiodarone, iopanoic acid and erythrosine had no effect on
      the thyroid ODC activity. CONCLUSIONS: These results suggest that LBI may exert
      its anti-goitrous effects, consisting of the inhibition of ODC activity and
      apoptosis, in the form of inorganic iodide in vivo.

PMID- 10911407
TI  - PCR based diagnosis of 21-hydroxylase gene defects in Slovak patients with
      congenital adrenal hyperplasia.
AB  - OBJECTIVE: To analyse 21-hydroxylase gene for 8 most common mutations in patients
      with salt-wasting type of congenital adrenal hyperplasia. METHODS: Allele
      specific PCR performed on 8 salt-wasting CAH patients and their 23 healthy
      relatives. RESULTS: Two patients were homozygous for 8 bp deletion in exon 3,
      while 6 patients were homozygous for intron 2 splice mutation. Mutant allele for
      splice mutation was found also in both parents of patients with this type of
      mutation. CONCLUSIONS: These preliminary results show that only two mutations, 8
      bp deletion in exon 3 and splice mutation in intron 2, were present in this group
      of Slovak patients with salt-wasting type of congenital adrenal hyperplasia.

PMID- 10911408
TI  - The influence of thyroxine on intensity of energy metabolism in bone marrow
      myeloid cells and neutrophilic polymorphonuclear leukocytes of neonatal pig.
AB  - OBJECTIVES: To investigate the participation of thyroxine in the regulation of
      energy metabolism in neutrophilic polymorphonuclear leukocytes and their bone
      marrow precursors. MATERIALS AND METHODS: The influence of L-thyroxine (T4; 4
      mg/kg every 12 hr from day 2 to 10 of age) was estimated on the activity of
      hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), lactate
      dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), NADP-dependent
      isocitrate dehydrogenase (ICDH) and cytochrome C-oxidase in bone marrow myeloid
      cells and circulating neutrophils of 3, 5 and 10 day (d) old piglets. Serum T4
      and 3,5, 3'-triiodothyronine (T3) concentrations were estimated at every stage of
      experiment by radioimmunoassay. Bone marrow cells of myeloid lineage and blood
      neutrophilic polymorphonuclear leukocytes were separated by differential
      centrifugation of haematopoietic cell suspension using Ficoll-Hypaque gradients.
      RESULTS: The hyperthyroid status resulted in significant increase in PFK and LDH
      activity in myelokaryocytes of 3 and 3-5 d piglets, while the activity of HK and
      PK in the cells of 3-10 d animals remained unchanged. Moreover, ICDH activity in
      myelokaryocytes increased on day 10 and that of cytochrome C oxidase in bone
      marrow cells at all intervals. Marked increase in HK and LDH activity on day 3-5
      was found also in blood polymorphonuclear granulocytes, while PFK and PK activity
      was increased during the whole period. At the same time even the increase in ICDH
      and cytochrome C-oxidase activity was observed, respectively, in 3 and 5-10 d old
      piglet neutrophils. Besides that, T4 inhibited G-6-PDH activity in myeloid cells
      on day 3 to 10 and did not influence the enzyme activity in circulating
      leukocytes. CONCLUSIONS: The administration of T4 resulted in preferential
      stimulation of oxidative stages of carbohydrate catabolism in myelocaryocytes,
      while the activity of glycolytic enzymes in these cells was less affected. On the
      contrary, the enzymes of glycolysis in blood neutrophils showed higher
      sensitivity to T4 action as compared to catalysts of oxidative reactions. The
      intensity of pentose phosphate pathway seems to be inhibited in bone marrow
      myelocaryocytes of T4 treated animals, while that in blood leukocytes remained
      unaffected.

PMID- 10911410
TI  - Histopathology of mammary tumours in female rats treated with 1-methyl-1
      nitrosourea.
AB  - OBJECTIVE: To induce, evaluate and classify advanced stages of mammary gland
      tumours induced by MNU. METHODS: Female Sprague-Dawley rats were injected
      intraperitoneally with 1-methyl-1-nitrosourea (MNU; 50 mg.kg-1) on the day 33,
      40, 47, 54 and 61 of age in the first experiment and on 50th and 113th day in the
      second experiment. On the 117th day (first experiment) and on the 153rd day of
      age (second experiment) the rats were sacrificed by decapitation and their
      mammary glands were evaluated both macroscopically and microscopically for the
      presence of grossly detectable mammary tumours. Mammary tumours were classified
      according to Russo et al. (1990). RESULTS AND CONCLUSIONS: The final incidence of
      palpable carcinomas was ranging from 60 % to 76 %. All microscopically evaluated
      tumours were malignant. Among the total number of lesions classified the
      percentage of invasive tumours ranged from 35 % to 44 %. No metastases were
      observed in other organs in MNU treated animals.

PMID- 10911409
TI  - Methimazole protection against oxidative stress induced by hyperthyroidism in
      Graves disease.
AB  - OBJECTIVE: To examine the dynamics of oxidative stress in patients with
      hyperthyroidism before and during the treatment with methimazole using the
      measurement of conjugated dienes, malondialdehyde, and Schiff bases in blood
      serum. METHODS: In eight female patients with diagnosed Graves disease and 8
      healthy control subjects (7 females and one male) several parameters of oxidative
      stress (the level of conjugated dienes [CD], malondialdehyde [MDA] and Schiff
      bases [SB]) were estimated before and during the treatment with methimazole
      (Metizol -POLFA) as well as by hormonal and immunological tests. In addition,
      serum levels of TSH, free thyroxine (FT4), free triiodothyronine (FT3),
      antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-Tg) and low
      density lipoprotein-cholesterol fraction (LDL-Ch) were estimated. RESULTS: We
      observed increased concentrations of free thyroxine (FT4) and free
      triiodothyronine (FT3), as well as of antithyroperoxidase (anti-TPO) and
      antithyroglobulin (anti-Tg) antibodies. At the same time, TSH level was
      significantly suppressed. The concentrations of thyroid hormones and of TSH
      normalised after the methimazole treatment. The examined parameters, i.e., CD,
      MDA, and SB, were evaluated as proportions of each of them to the level of low
      density lipoproteins-cholesterol fraction (LDL-Ch). This fraction of cholesterol
      contains many polyunsaturated fatty acids, being a substrate for the peroxidation
      of lipids. Additionally, the CD/MDA ratio was calculated. CONCLUSIONS: The
      increase of the CD/LDL ratio in Graves hyperthyroidism and its normalisation in
      the course of the treatment with methimazole suggests that the drug can be
      protective against the oxidative stress induced by overproduction of thyroid
      hormones. The ratio of CD/MDA decreased in all the patients, as compared to the
      control group, showing a high speed of lipid peroxidation.

PMID- 10911411
TI  - Vitamin A, vitamin E and carotenoid status and metabolism during ageing:
      functional and nutritional consequences (project proposal).

PMID- 10911412
TI  - Research productivity: time to lead.

PMID- 10911413
TI  - Relationship among balance impairments, functional performance, and disability in
      people with peripheral vestibular hypofunction.
AB  - BACKGROUND AND PURPOSE: Physical therapy interventions are often based on assumed
      relationships among impairments, functional performance, and disability. The
      purposes of this study were (1) to describe balance impairments, functional
      performance, and disability in subjects with unilateral peripheral vestibular
      hypofunction (UVH) and bilateral peripheral vestibular hypofunction (BVH), (2) to
      examine the relationship among these factors, and (3) to determine whether
      disability can be explained by commonly used tests of balance and functional
      performance. SUBJECTS: Participants were 85 subjects (mean age=62.5 years,
      SD=16.5) with UVH (n=41) or BVH (n=44) diagnosed by vestibular function tests and
      clinical examination. METHODS: Each subject completed the Dizziness Handicap
      Inventory (DHI) to obtain a measure of disability. Functional performance was
      measured with a modified Timed Up & Go Test (TUG). Balance impairments were
      measured with computerized posturography and balance tests. Descriptive
      statistics, correlational analyses, and stepwise regressions were performed.
      RESULTS: Subjects with BVH had poorer balance but similar TUG scores and
      perceived levels of disability, as compared with subjects with UVH. Weak to
      moderate correlations existed among balance measurements, TUG scores, and DHI
      scores. Balance impairments and TUG scores together explained 78% of the variance
      in DHI scores of the subjects with BVH, whereas balance impairments alone
      explained 13% of the variance in DHI scores of the subjects with UVH. CONCLUSION
      AND DISCUSSION: Balance impairments and functional performance appear to be more
      closely related to disability in individuals with BVH as compared with those with
      UVH. Clinical tests of balance impairments and functional performance appear to
      be useful in explaining disability.

PMID- 10911414
TI  - Comparison of the University of California-Los Angeles Shoulder Scale and the
      Simple Shoulder Test with the shoulder pain and disability index: single
      administration reliability and validity.
AB  - BACKGROUND AND PURPOSE: Shoulder scales are often used to evaluate treatment
      efficacy, yet little is known about the psychometric properties of these scales.
      Only one scale has undergone psychometric scrutiny: the Shoulder Pain and
      Disability Index (SPADI). This study compared 2 shoulder measures-the University
      of California-Los Angeles (UCLA) Shoulder Scale and the Simple Shoulder Test
      (SST)-with the SPADI. SUBJECTS: One hundred ninety-two patients with shoulder
      disorders were recruited from one physician's office to complete the self-report
      sections of the 3 scales. METHODS: Cronbach alpha values and standard errors of
      measurement (SEM) were calculated for each of the multi-item subscales. Validity
      was examined through calculation of correlation coefficients among the 3 scales.
      Factor analysis was completed to assess the underlying constructs of the SPADI
      and the SST. RESULTS: Cronbach alpha values ranged from.85 to.95. The SEM values
      for the multi-item scales ranged from 4.75 to 11.65. Evidence for validity to
      reflect function was indicated by the correlation between the SST and the SPADI
      disability subscale. The factor analysis of the SPADI revealed loading on 1
      factor, whereas the SST loaded on 2 factors. CONCLUSION AND DISCUSSION: All
      scales demonstrated good internal consistency, suggesting that all items for each
      scale measure the same construct. However, the SEMs for all scales were high.
      Factor loading was inconsistent, suggesting that patients may not distinguish
      between pain and function.

PMID- 10911415
TI  - Effects of immobilization on plantar-flexion torque, fatigue resistance, and
      functional ability following an ankle fracture.
AB  - BACKGROUND AND PURPOSE: The goal of this investigation was to study the recovery
      of ankle plantar-flexor peak torque, fatigue resistance, and functional ability
      (stair climbing, walking) following cast immobilization in patients with ankle
      fractures. SUBJECTS: The participants were 10 patients who underwent open
      reduction-internal fixation and 8 weeks of cast immobilization following a
      fracture of the ankle mortise and 10 age- and sex-matched, noninjured comparison
      subjects. METHODS: Plantar-flexor torque and fatigue resistance were measured at
      1, 5, and 10 weeks of rehabilitation using an isokinetic dynamometer. Ankle
      plantar-flexor peak torque and fatigue resistance were correlated to timed
      ambulation, timed stair climbing, and unilateral heel-rises. RESULTS: Following
      immobilization, plantar-flexor peak torque was decreased at all angular speeds
      and positions. The decrease in peak torque was associated with an increase in
      fatigue resistance. With rehabilitation, ankle plantar-flexor torque and fatigue
      resistance normalized. Regression analysis revealed a strong relationship between
      plantar-flexor peak torque and functional measures. By 10 weeks post
      immobilization, peak torque, fatigue resistance, and all measures of functional
      performance had returned to control levels. CONCLUSION AND DISCUSSION: The
      decrease in muscle performance, functional ability, and fatigue resistance
      induced by 8 weeks of cast immobilization can be reversed with 10 weeks of
      supervised physical therapy. In addition, this study demonstrated that ankle
      plantar flexor torque is a good predictor of stair-climbing and walking
      performance in patients with ankle fractures.

PMID- 10911416
TI  - Submaximal exercise testing: clinical application and interpretation.
AB  - Compared with maximal exercise testing, submaximal exercise testing appears to
      have greater applicability to physical therapists in their role as clinical
      exercise specialists. This review contrasts maximal and submaximal exercise
      testing. Two major categories of submaximal tests (ie, predictive and performance
      tests) and their relative merits are described. Predictive tests are submaximal
      tests that are used to predict maximal aerobic capacity. Performance tests
      involve measuring the responses to standardized physical activities that are
      typically encountered in everyday life. To maximize the validity and reliability
      of data obtained from submaximal tests, physical therapists are cautioned to
      apply the tests selectively based on their indications; to adhere to methods,
      including the requisite number of practice sessions; and to use measurements such
      as heart rate, blood pressure, exertion, and pain to evaluate test performance
      and to safely monitor patients.

PMID- 10911417
TI  - Neuroanatomical substrates of functional recovery after experimental spinal cord
      injury: implications of basic science research for human spinal cord injury.
AB  - Human spinal cord injury (SCI) is a devastating condition that results in
      persistent motor deficits. Considerable basic and clinical research is directed
      at attenuating these deficits. Many basic scientists use animal models of SCI to
      (1) characterize lesion development, (2) determine the role of spared axons in
      recovery, and (3) develop therapeutic interventions based on these findings. In
      this article, current research is reviewed that indicates: (1) most individuals
      with SCI will have some sparing of white matter at the lesion epicenter even when
      the lesion appears clinically complete, (2) even minimal tissue sparing has a
      profound impact on segmental systems and recovery of function, and (3)
      facilitatory intervention such as weight bearing and locomotor training after SCI
      may be more effective than compensatory strategies at inducing neuroplasticity
      and motor recovery. Body weight supported treadmill step training is discussed as
      an example of new facilitatory interventions based on basic science research
      using animal models.

PMID- 10911418
TI  - Spinal manipulation.

PMID- 10911420
TI  - [Fine needle aspiration biopsy of mediastinal masses guided by computed
      tomography--summary of 63 patients].
AB  - Progress in diagnostic radiology and pathology during the past decade has changed
      the approach to diagnosis of mediastinal masses. Diagnosis by CT-guided needle
      biopsy (CTNB) has replaced open biopsy and mediastinoscopy, CTNB of mediastinal
      masses is accurate, reliable and safe. It is done under local anesthesia, in
      ambulatory patients and is tolerated well. Between July 1987 and April 1997 we
      performed 67 biopsies in 63 patients aged 6-86 years; 33 were women (average age
      40.8 years) and 30 men (average age 38.3 years). 57 of 67 biopsies were core
      biopsies for histologic examination and 10 were cytologic biopsies. In this
      report we concentrate on the 57 core biopsies. 41 of the biopsies were
      diagnostic; in 3 of them no evidence of malignancy was found. In 38 of the
      biopsies a tumor, malignant or benign, or an inflammatory process was diagnosed.
      In 24 of the biopsies the diagnosis was lymphoma. In 16 there was not enough
      material for diagnosis. We repeated the biopsy in 4 of the latter due to high
      suspicion of malignancy and reached a diagnosis in all 4 of them. In 6 the
      diagnosis was reached only on operation. The biopsies were from all compartments
      of the mediastinum. There were no complications such as pneumothorax or bleeding,
      except for 1 case of mild hemoptysis. In conclusion, CTNB of mediastinal lesions
      is accurate, safe and relatively cheap. In 72% a diagnosis was reached in the
      first attempt and a second attempt raised the diagnostic rate to 79%. We believe
      that CTNB should be the first step in tissue diagnosis of mediastinal masses,
      including those under high suspicion of lymphoma.

PMID- 10911419
TI  - [Experience at Sheba Hospital in oncogenetic counseling and genetic testing of
      women with a high risk for breast and ovarian cancer].
AB  - There is inherited predisposition to breast and ovarian cancer in 5-10% of all
      women with these diseases. Germline mutations in BRCA1 and BRCA2 presumably
      account for most of the genetically susceptible individuals. We summarize 2 years
      of experience in counseling and testing for inherited predisposition to these
      cancers. 597 women (from 320 families) have been evaluated since August 1995. 242
      were evaluated for inherited predisposition to breast and ovarian cancer. One
      third had clear-cut evidence of familial background. 74 families were of
      Ashkenazi origin; the age range of breast cancer was 30-35, of ovarian cancer 40
      45. In 80% of families other cancers were also noted in first degree family
      members, including lung, colon, and prostate cancer and leukemia. Genetic testing
      revealed that 45% of affected and 25% of unaffected women were carriers of a
      mutation in BRCA1 or BRCA2: 67/90 185delAG (BRCA1), 12/90 6174delT (BRCA2), and
      4/90 of 5382insC (BRCA1). In addition, a novel mutation in exon 11 of BRCA1 was
      detected, carried by 7/90 women. The experience gained in oncogenetic counseling
      and genetic testing for inherited cancer predisposition will eventually enable
      determining an optimal, rational therapeutic regimen in carriers of mutations.

PMID- 10911421
TI  - [Topical photodynamic therapy in basal and squamous cell carcinoma and penile
      Bowen's disease with 20% aminolevulinic acid, and exposure to red light and
      infrared light].
AB  - Photodynamic therapy (PDT) is a noninvasive selective therapy for a specific
      group of skin tumors. 5-aminolevulinic acid 20% in a water-in-oil cream base was
      applied to the tumors as a photosensitizer and was followed after 12 hours by
      exposure to a high output light source emitting red (585-720 nm; 150 mW/cm2) and
      near infrared irradiation (1.25-1.6 mm; 50 mW/cm2) for 10-15 minutes (VersaLight,
      incoherent filtered light source). Complete responses were achieved after 1-3
      treatments in 26/31 lesions of superficial or small nodular basal cell carcinoma
      (BCC) and 4/5 in superficial, squamous cell carcinoma (SCC) lesions. There was a
      patient with Bowen's disease of the penis. Follow-up was for 12-24 months. This
      noninvasive, nearly painless treatment gives excellent therapeutic and cosmetic
      results. Our data show its efficacy for certain subtypes of BCC, SCC and Bowen's
      disease. Further studies will determine the exact cure and recurrence rates with
      this modality and compare it to other modes of skin cancer therapy.

PMID- 10911422
TI  - [Taxol (paclitaxel) as second-line therapy in breast and ovarian cancer].
AB  - Results of chemotherapy with taxol (paclitaxel) in 55 patients with recurrent
      breast and ovarian cancer were reviewed. Taxol was given as a 3-hour infusion,
      every 3 weeks, on an outpatient basis. There was complete or partial response in
      8 patients (23%) with breast cancer and 10 (50%) with ovarian cancer. Performance
      status and previous response to adriamycin were important prognostic factors.
      Toxicity was manageable. Treatment had to be stopped for hypersensitivity
      reactions in only 2 patients. Taxol given in an ambulatory clinic is safe and
      effective.

PMID- 10911423
TI  - [Sudden death from asthma in childhood, is it preventable?].
AB  - Sudden death from asthma is rare but occurs in the young age group. We recently
      faced this rare situation when 3 asthmatic children were dead on arrival at the
      local emergency room. All 3 had been treated with beta-2 agonist inhalation on a
      regular basis, without anti-inflammatory treatment, 2 of the children died while
      inhaling the beta-2 agonist. It is important that there be clear guidelines and
      full education about the management of asthma, during and between exacerbations,
      to prevent such deaths.

PMID- 10911424
TI  - [Cyclic vomiting syndrome in children].
AB  - Cyclic vomiting syndrome in children is a manifestation of various etiologies,
      including gastroenterological and renal disorders, central and autonomic nervous
      system abnormalities, as well as metabolic and endocrine dysfunction. Frequently
      no organic cause is found. Personality profiles of children with cyclic vomiting
      reveal perfectionism, competitiveness, and aggressive behavior. Vomiting attacks
      have been induced by anxiety and excitement in patients with cyclic vomiting. We
      describe an 8-year-old girl with cyclic vomiting, frequently associated with
      occipital headaches, photophobia or dizziness. Psychiatric evaluation indicated a
      generalized anxiety disorder.

PMID- 10911425
TI  - [Toxic optic neuropathy caused by methanol poisoning].
AB  - A 40-year-old woman attempted suicide by drinking methanol. Her visual acuity
      began to deteriorate 36 hours later and was found to be 6/60 in her right eye
      with no light perception in the left. No systemic manifestations other than the
      eye symptoms were found. In the following months visual acuity improved without
      specific therapy. 2 months following the methanol, visual acuity was 6/6 in the
      right eye and finger-counting at 1 meter in the left eye. There was pronounced
      optic atrophy in the left eye, as well as a central defect in the left visual
      field due to the methanol toxicity.

PMID- 10911426
TI  - [New treatments in AIDS--a true revolution].

PMID- 10911427
TI  - [Immunological reactivity of gangliosides in neuropathies].

PMID- 10911428
TI  - [Stress incontinence--diagnosis and management].

PMID- 10911429
TI  - [Initial treatment of primary open angle glaucoma: medication, laser or
      surgery?].

PMID- 10911430
TI  - [Progesterone and the risk of arterial and venous thrombosis].

PMID- 10911431
TI  - [Brenner tumor and tumors of transitional epithelium in the Mullerian system].

PMID- 10911432
TI  - [Growth hormone and the aging process].

PMID- 10911433
TI  - [Peritoneal tuberculosis--clinical features, diagnosis and treatment].

PMID- 10911434
TI  - [Rasmussen's encephalitis].

PMID- 10911435
TI  - [From biblical stories--multiple pregnancy and fetal sex determination in
      biblical times].

PMID- 10911436
TI  - [Changes in structure and process components of trauma care in emergency
      departments in Israel--Part I].
AB  - In recent years there have been tremendous efforts to improve primary trauma
      care. The Ministry of Health and other authorities have invested in new trauma
      facilities in various hospitals. A nationwide survey with regard to structure and
      function of emergency departments was carried out. Compared to a similar survey
      conducted in 1992, significant progress in quality and quantity of equipment at
      various emergency departments was demonstrated. However, there are still
      differences between various hospitals. A drive to standardize trauma care will
      undoubtedly contribute to improvement in care of the injured.

PMID- 10911437
TI  - [A story about the King of Denmark's horse, a mechanical ventilator and a
      righteous man of nations].

PMID- 10911438
TI  - [Brittle juvenile diabetes--a personal view].

PMID- 10911440
TI  - [The surgeon and the Emperor--a humanitarian on the battlefield].
AB  - The Baron Dominique-Jean Larrey, one of the greatest names in military surgery,
      participated as Chief Surgeon in all the Napoleonic campaigns. He developed the
      concept of early evacuation from the battlefield, and of immediate treatment of
      the wounded, even under fire. He implemented improved surgical techniques and
      improved wound care that were followed by surgeons all over Europe. His devotion
      to wounded soldiers crossed national boundaries and became a way of life. Here is
      an account of Larrey's involvement in the aftermath of the Battles of Lutzen and
      Bautzen (May-June 1813), when many soldiers were accused of self-mutilation and
      were about to be executed. He dared to oppose, singlehanded, the Emperor, the
      highest military authorities and their concurring physicians and surgeons, armed
      only by his undisputed honesty, professional authority and exceptional reputation
      won over years of devotion to wounded soldiers. Larrey saved the lives of many
      soldiers and set an example of unbent ethical integrity.

PMID- 10911439
TI  - [Risk of transmission of viral disease by needle punctures and cuts in hospital
      health care workers].
AB  - The accidental exposure of the health care workers (HCW) to blood and blood
      products constitutes a danger for transmission of blood-borne pathogens and the
      development of severe diseases. Most attention is focused on exposure to the
      viruses of hepatitis B, C and human immunodeficiency. The objectives of this
      prospective study were to determine the rate of exposure of our HCW to blood and
      blood products; to define the high risk groups; and to establish recommendations
      to prevent transmission or reduce the risk of exposure to these viruses. During
      the year 1996, 103 injuries from needle-puncture or other sharp objects were
      reported to our infectious diseases control unit. Most of those injured were
      women. 58.4% of the events occurred in the vicinity of the patient. The source of
      exposure was known in 60% of the cases. 73.8% of those injured had already been
      immunized against hepatitis B. The departments in which most exposures occurred
      were the operating theater (12.5%), medical departments A (10.6%) and B (9.6%),
      and the emergency department (7.7%). Nurses were at highest risk, constituting
      47% of those injured. Our recommendations are that a continuous teaching program
      be established for the high risk groups; that HCW be urged to report every event
      of exposure; and to encourage HCW to undergo active immunization against
      hepatitis B.

PMID- 10911441
TI  - [Empirical treatment of urinary tract infections in the delivery room--findings
      and desires].
AB  - Urinary tract infection (UTI) is the most common bacterial infection during
      pregnancy. In prenatal and delivery wards treatment is usually started at once in
      pregnant women with symptoms suggesting UTI, but there is no uniformity as to
      treatment. We surveyed such treatment in the delivery rooms throughout Israel,
      and whether the treatment differed in simple cystitis as opposed to
      pyelonephritis. Results of positive urine cultures from symptomatic parturients
      admitted here during 1995-1996 were examined. There were 17 different empiric
      treatment protocols in 28 delivery rooms, whose daily cost ranged from 1-119 NIS.
      We present the antimicrobial sensitivity of 156 bacteria isolated from the
      urinary cultures from pregnant women in our prenatal ward. Based upon urinary
      flora, sensitivity and daily cost, we suggest a protocol for empiric treatment.
      We recommend first and second generation cephalosporins for treatment of simple
      lower (UTIs), while gentamicin is suggested for treatment of clinical
      pyelonephritis during pregnancy. There is no medical nor economic justification
      for the multiplicity of empiric treatment protocols currently used. Considering
      our results, our protocol is cost-effective for the empiric treatment of UTI in
      hospitalized parturients and in the community as well.

PMID- 10911442
TI  - [Diagnosis of hyperprolactinemia: determination of prolactin level at rest].
AB  - We present 3 women who were referred for evaluation of stress-related mild-to
      moderate hyperprolactinemia. This frequent finding may mistakenly be considered a
      clinical problem, and lead to inappropriate investigation and therapy. We
      emphasize the importance of serial blood sampling for prolactin determination. We
      collected blood samples repeatedly under resting conditions from an indwelling
      venous brachial catheter, every 30 minutes for a total of 6 samples. All 3
      patients had normal prolactin levels 30-60 minutes after starting the test.
      Neither further investigation nor medical therapy were needed and these anxious
      patients were reassured that their hyperprolactinemia was factitious.

PMID- 10911443
TI  - [Nasopharyngeal colonization with Streptococcus pneumoniae in pediatric
      respiratory infections].
AB  - During the winter of 1995, nasopharyngeal colonization of Streptococcus
      pneumoniae was evaluated in 204 children with respiratory infection and 107
      normal control children. There was no difference in gender or mean age between
      the groups, and no difference in carrier rate between sick (24.5%) and normal
      (22%) children (p = 0.6). Carrier rates were 19%, 32%, 31% and 17% at 6, 12, 24
      and 48 months, respectively. Penicillin-resistant pneumococci (PRP) were found in
      42% of sick and 16.6% of normal children, (p < 0.05). Resistance to more than 2
      antibiotics was found in 28% of sick and in 12.5% of normal children. PRP were
      found in 67% and 34% of sick children with and without prior antibiotic treatment
      (p < 0.05). We conclude that there is no difference in the carrier rate of
      Streptococcus pneumoniae between sick and normal children. However, the high
      prevalence of PRP in children with respiratory infections is probably due to
      prior antibiotic treatment.

PMID- 10911444
TI  - [Concept management in penetration of unusually shaped foreign bodies into
      extremities].
AB  - During routine emergency room work penetration by foreign objects is frequently
      encountered, some of which may be very irregular in shape. These may cause
      further damage if inappropriately removed. It is important to perform a proper X
      ray survey.

PMID- 10911445
TI  - [Spontaneous internal jugular vein thrombosis complicating chronic pulmonary
      disease].
AB  - Spontaneous internal jugular thrombosis is a rare vascular disorder. It usually
      occurs as a result of external pressure due to a tumor, infection or as a result
      of damage to the vessel wall after trauma or central venous catheterization. We
      report a 35-year-old woman who suffered from severe pulmonary hypertension due to
      chronic cystic lung disease. She was admitted due to sudden, severe, right-sided
      neck pain. Internal jugular occlusion by a thrombus was demonstrated by
      ultrasound and CT-scans but no apparent cause was found. We postulated that the
      important factors in the development of her thrombosis were stasis due to
      pulmonary hypertension and high blood viscosity.

PMID- 10911446
TI  - [Miliary and reticulo-nodular pulmonary brucellosis].
AB  - Brucellosis is a classical zoonosis caused by a Gram-negative bacillus of the
      genus Brucella. Human brucellosis can either be acute or chronic and present with
      a variety of manifestations, mostly with fever and signs of musculo-skeletal
      involvement. It may be complicated by involvement of the cardiovascular, central
      nervous or genito-urinary systems. However, pulmonary brucellosis is a rare
      complication. We report a case of miliary and reticulo-nodular brucellar
      pneumonia with positive blood and sputum cultures and positive serological tests.
      To the best of our knowledge this is the first case to be reported from Israel of
      miliary pneumonia with sputum positive for brucellosis.

PMID- 10911447
TI  - [The diagnosis and treatment of Fournier's gangrene].
AB  - We treated 2 women and 8 men suffering from Fournier's gangrene during 1990-96. 2
      had diabetes, 1 suffered from ulcerative colitis and 1 was an alcoholic. In 8 of
      them the infection was triggered by a mixture of aerobic and anaerobic bacteria.
      Treatment consisted of repeated wide debridement and early colostomy. This
      aggressive approach resulted in relief of the septic signs within 24 hours and
      permitted early skin grafting of the wounds. 2 patients died due to sepsis that
      caused multiple organ failure. The 8 who survived were hospitalized for an
      average of 35 days. On follow-up examination 1-5 years later all patients had
      undergone closure of the colostomy and were completely rehabilitated. Fournier's
      gangrene is not rare in the geriatric population. We believe that early diagnosis
      and aggressive wide debridement, combined with early colostomy, are the keys to
      successful treatment.

PMID- 10911448
TI  - [Aphthous stomatitis as a first manifestation of Crohn's disease in a 5 year-old
      boy].
AB  - The incidence of Crohn's disease has risen dramatically over the past few years.
      The peak age of onset is in late adolescence, but it rarely occurs in the first
      few years of life. We describe a 5-year-old boy with recurrent bouts of fever,
      aphthous stomatitis, and anemia which did not respond to routine antibiotic
      therapy. It was only after a few months, when the characteristic symptoms of
      inflammatory bowel disease (IBD): abdominal pain and diarrhea appeared, that the
      diagnosis of Crohn's disease was made. This case illustrates the difficulty in
      diagnosing IBD in young children. The presenting symptoms of IBD in children are
      often nonspecific and extra-intestinal. There is usually a low index of suspicion
      by the physician as to the possibility of IBD in a young child.

PMID- 10911449
TI  - [A real threat to the profession].

PMID- 10911450
TI  - [Environmental factors and scleroderma].

PMID- 10911451
TI  - [Minimally invasive surgical procedures for female urinary stress incontinence].

PMID- 10911452
TI  - [MRCP--advanced imaging of the biliary and pancreatic ducts].

PMID- 10911453
TI  - [Diffuse idiopathic skeletal hyperostosis].

PMID- 10911454
TI  - [The role of jugular bulb catheters in the assessment of brain oxygenation].

PMID- 10911455
TI  - [Carbon dioxide angiography].

PMID- 10911456
TI  - [Body dysmorphic disorder].

PMID- 10911457
TI  - [Fecal impaction in the elderly].

PMID- 10911458
TI  - [The Hadassah physicians' "plot", from socialist principles to private practice].

PMID- 10911459
TI  - [Development of pulmonary hypertension and multi-valvular damage caused by
      appetite depressants].
AB  - Marked obesity is an independent risk factor for multi-system morbidity. The use
      of anorectic drugs is an aggressive strategy for weight reduction. It appears to
      be an easy way of dealing with the problem, because the patient needn't change
      his behavior. However, such treatment is not harmless. At the end of the 60's an
      outbreak of pulmonary hypertension was associated with the drug aminorex, and it
      was soon withdrawn from the market. 30 years later it became clear that new
      generation anorectic drugs (fenfluramine, dexfenfluramine, phentermine), which
      were being used world-wide, lead to both pulmonary hypertension and valvular
      damage. We describe a woman of 70 with both these complications which developed
      after prolonged anorectic therapy with a fenfluramine-phentermine combination.

PMID- 10911460
TI  - [The Mitrofanoff pouch in lower urinary tract reconstruction].
AB  - The Mitrofanoff principle, first described in 1980, consists of implanting a
      tubular organ such as the appendix, ureter, or fallopian tube into the wall of
      the bladder (or urinary reservoir) to create a non-refluxing, catherizable
      urinary conduit. Between 1993-1996, 7 men and 1 woman (aged 48-64, average 59)
      underwent radical cystectomy and urethrectomy combined with the creation of a
      MAINZ I urinary reservoir (based on the Mitrofanoff principle). In men the
      indication for the procedure was the diagnosis of invasive transitional cell
      carcinoma of the bladder with involvement of the prostatic urethra. All patients
      had refused urinary diversion to an ileal conduit because of its deleterious
      effect on the quality of life. In all patients the postoperative course was
      uneventful, apart from intraperitoneal urinary leakage from the reservoir in 1,
      successfully managed conservatively. The patients have gained full control of
      urinary drainage, performing intermittent self-catheterizations every 4-5 hours.
      In 3 patients there were difficulties with catheterization due to stenosis of the
      conduit, usually at the skin level. None have suffered leakage from the
      reservoir, during the day, even when it was full. Our experience shows that
      creation of a continent urinary reservoir according to the MAINZ I technique is
      an excellent surgical solution for patients in whom the creation of an orthotopic
      reservoir is impractical. The use of the umbilicus as a stomal site preserves
      normal body image and thus does not interfere with quality of life as in those
      undergoing radical cystectomy.

PMID- 10911461
TI  - [Willingness to donate organs towards the 2000s--results of a survey of attitudes
      among Israeli Jews].
AB  - A public opinion survey of Israeli Jewish adults (September) showed a large
      potential willingness to donate organs after death, while only a third of the
      sample was opposed. Nevertheless, only a very minor proportion held donor's
      cards, and over half expressed opposition to holding a donor card. As to next-of
      kin's organs, when the wishes of the relative were not known, a quarter of the
      sample opposed, a quarter agreed, and the remaining half hesitated to make a
      decision. Willingness to donate was not correlated with gender, age or income,
      but was related to religiosity: the more religious, the less willing to donate.
      And the religious reason was the salient one given for hesitation about donating,
      although there were many who could give no reason for their hesitation. Family
      members, doctors and rabbis (in ascending order) influenced willingness to
      consent to next-of-kin donations.

PMID- 10911462
TI  - [Use of restraints in a general hospital--a picture of the situation].
AB  - 28 in-patient units were surveyed during a 5-day period to determine the extent
      of the use of physical restraints in hospitalized patients. Information was
      gathered on the characteristics of restrained patients and indications for use
      and removal of restraints, patterns and means of restraints, monitoring, and
      written notations. 31 different patients (6% of those surveyed) were restrained
      in 13 units during the 5 days of the survey, an average of 15 (3%) daily.
      Characteristics of restrained patients were: age 70 and over requiring emergency
      hospitalization, reduced level of consciousness, limitation of mobility,
      incontinence, history of 2 or more chronic diseases, requiring multiple drugs,
      and use of multiple medical devices. Bilateral, soft hand restraints were most
      often used to prevent patients from removing tubes. Nurses initiated the decision
      to apply or remove restraints, which were usually removed as the patients'
      condition improved. Written policies were lacking regarding monitoring and follow
      up of restrained patients. Clearly written policies and increased staff awareness
      of potential hazards may reduce the use of restraints and the length of time they
      are employed.

PMID- 10911464
TI  - [Serotonin re-uptake inhibitors as primary therapy for carotid sinus
      hypersensitivity].
AB  - Carotid sinus syndrome is a well-recognized cause of unexplained syncope in older
      patients, and may, lead to significant morbidity due to trauma from falls. Dual
      chamber pacing has been shown to be effective in relieving symptoms due to
      bradycardia, but not due to vasodepressor response. We report an 84-year-old man
      with recurrent syncope due to carotid sinus hypersensitivity. He was treated only
      with a serotonin reuptake inhibitor and was symptom-free after 3 weeks of
      therapy. He has remained symptom-free for the past year.

PMID- 10911463
TI  - [Normotensive hydrocephalus complicating recurrent E. coli meningitis].
AB  - E. coli meningitis is a disease that occurs in predisposed patients, either as a
      result of trauma or in neonates after neurosurgery. Recurrent E. coli meningitis
      in an adult without any apparent predisposition is uncommon, and hydrocephalus
      complicating bacterial meningitis is even more rare. We report a unique case of a
      67-year-old alcoholic man who had had 2 consecutive episodes of E. coli
      meningitis within 2 months. In both episodes there was a favorable response to
      ceftriaxone. However, normotensive hydrocephalus appeared a few weeks later, with
      mental and physical deterioration.

PMID- 10911465
TI  - [Ultrasonographic imaging of superior sagittal thrombosis].
AB  - Ultrasonographic findings of superior sagittal sinus thrombosis include dilated
      and hyperechoic sinus (direct imaging of the thrombus). No flow should be
      demonstrated by the various Doppler techniques. In the deeper sinuses, if the
      thrombus can not be visualized after a negative Doppler study, MR imaging is
      recommended. Recanalization and reflow can be demonstrated on follow-up study.

PMID- 10911466
TI  - [Methotrexate treatment in refractory juvenile rheumatoid arthritis].
AB  - The mean time from initiation of methotrexate (MTX) treatment of juvenile
      rheumatoid arthritis (JRA) to partial remission of clinical symptoms and total
      clinical remission was assessed. 9 girls and 8 boys, from 3 to 18 years of age
      (mean 11.4 +/- 5.4) with active JRA by American College of Rheumatology (ACR)
      criteria (5 systemic, 8 polyarticular and 4 pauciarticular disease onset), who
      failed to respond to adequate courses of non-steroidal anti-inflammatory drugs
      (NSAID), steroids or disease-modifying drugs were studied. Clinic visits were
      scheduled at monthly intervals for physical and laboratory assessment of disease
      activity and drug safety. Partial response to MTX was defined a 25% reduction of
      the active joint count and/or articular severity score. Total clinical remission
      was defined as in adult rheumatoid arthritis. The duration of disease activity
      until enrollment ranged from 6 months to 14 years (4.5 +/- 3.7 yr); duration of
      therapy was 3 months to 3 years (14.6 +/- 9.3 mo) and dosage ranged from 5 to 15
      mg/m2/week. Prednisone in doses below 10 mg/day and NSAID were permitted. 14 of
      17 patients (82%) had a 25% reduction in joint activity after 6 weeks to 4 months
      (9.2 +/- 3.2 weeks); 10 (59%) went into full clinical remission after 5 to 26
      months (14.3 +/- 9 months); 3 relapsed after an initial response to treatment,
      and 4 (23%) did not respond to MTX. The non-responders were males who required
      higher doses of prednisone (p < 0.0001). MTX appears to be effective therapy for
      children with JRA. An initial response can be expected in most patients after 9
      weeks of treatment, and full clinical remission occurs after a mean of 14 months.

PMID- 10911467
TI  - [Is carotid endarterectomy without prior angiography justified?].

PMID- 10911468
TI  - [Valvular heart disease and primary pulmonary hypertension associated with
      fenfluramine-phentermine].

PMID- 10911469
TI  - [Hyperhomocysteinemia, complicated pregnancies and neural tube defects].

PMID- 10911470
TI  - [Biphosphonates as a treatment for arresting metastasis. A new indication?].

PMID- 10911471
TI  - [Osteopetrosis--new insights in pathophysiology and treatment modalities].

PMID- 10911472
TI  - [Prevention and management of local recurrence of rectal carcinoma].

PMID- 10911473
TI  - [Atrial septal aneurysm as a possible cause of cardiac embolism].

PMID- 10911474
TI  - [Psychiatric and epidemiologic projections of sexual abuse of children and
      adolescents].

PMID- 10911475
TI  - [The challenge: diagnosis and treatment of chronic scrotal pain].

PMID- 10911476
TI  - [Birth deformities in diabetic mothers--clinical and experimental aspects].

PMID- 10911477
TI  - [Syncope in children and adolescents: diagnosis, work-up and therapy].

PMID- 10911478
TI  - [Synovial fluid analysis in gout].

PMID- 10911479
TI  - [Two-hundred years since the birth of Thomas Hodgkin (1798-1886)].

PMID- 10911480
TI  - [Ignaz P Semmelweis: forgotten hero].

PMID- 10911481
TI  - [Laniado Medical Center] [In Process Citation]

PMID- 10911482
TI  - [Evaluation of predictive factors for stroke rehabilitation].
AB  - Our objective was to assess the functional disability of stroke patients by the
      functional independence measure (FIM) and to examine predictive factors for
      successful rehabilitation. In 127 consecutive stroke patients efficacy of FIM was
      23.9 +/- 188, efficiency 0.54 +/- 0.45, and 81.9% of patients returned home.
      Functional improvement was statistically significant (p < 0.001) in all FIM
      domains. Multivariate analysis showed that improvement in FIM score was
      significantly greater in the younger, among the married, the hemiparetic, and
      those with an admission FIM of 40-60, while efficiency was related only to type
      of diagnosis. In addition, the hemiparetic were 3.3 times more likely to return
      home than the hemiplegic. We conclude that rehabilitation priorities should be
      directed towards patients younger than 75 years and to those with an admission
      FIM of 40-60 points. The results of this study reaffirm the usefulness of the FIM
      index in assessing stroke rehabilitation.

PMID- 10911483
TI  - [Characteristics, management and prognosis of acute myocardial infarction in
      Israel in the 1990s. Israeli Survey Group on Acute Myocardial Infarction].
AB  - From 1990 to 1996 we conducted consecutive 2-month surveys in all CCUs (n = 26)
      in Israel. The aim was to compare the characteristics, management, and prognosis
      of patients with acute myocardial infarction (AMI) between the 4 surveys. Patient
      characteristics were similar in all surveys. About 75% of patients were males and
      had a first MI. Mechanical and arrhythmic complications decreased slightly
      between 1990 and 1996. In contrast, frequency of treatment with thrombolysis,
      aspirin, beta-blockers and ACE-I, as well as coronary interventional procedures,
      increased tremendously. In parallel, 30-day and 1-year mortality decreased
      significantly, from 16.5% and 22.5%, respectively, to 9.0% and 13.9%. After
      multiple adjustment for factors associated with mortality, the 30-day relative
      risk of death for patients hospitalized in 1992, 1994 and 1996 was 0.79 (95% CI
      0.59-1.08), 0.75 (95% CI 0.56-1.01) and 0.54 (95% CI 0.39-9.74), respectively, as
      compared with 1990. Although there is no direct proof that changes in management
      of AMI are related to the reduction in mortality seen during the course of the
      surveys, the association seems likely.

PMID- 10911484
TI  - [Video assisted thoracoscopic surgery (VATS) for spontaneous pneumothorax].
AB  - We report our initial experience with thoracoscopic surgery in the treatment of
      spontaneous pneumothorax in 14 patients, mean age 30.7 years. 7 were operated
      following 2 episodes of spontaneous pneumothorax, 6 after their first episode,
      and 1 after multiple episodes. All underwent bleb resection, pleurodesis and tube
      thoracostomy; in 1 we converted to a limited thoracotomy (93% success rate). Only
      oral analgesia was required for postoperative pain control and patients were
      discharged 2.6 days after surgery, on average. The apparent superiority of
      thoracoscopic over conventional, even limited, thoracotomy seems to justify such
      therapy even during the first episode.

PMID- 10911485
TI  - [Bowel-lengthening in a newborn with short bowel syndrome].
AB  - Advances in parenteral nutrition and supportive therapy have led to improvement
      in survival of babies with short-bowel syndrome. Those whose intestinal mass is
      very unlikely to be adequate should have surgical therapy as soon as possible,
      before they develop the complications of long-term parenteral nutrition or
      significant enteritis. We present a newborn with short-bowel syndrome due to
      prenatal midgut volvulus. At operation the remaining viable jejunum, 15 cm long,
      was anastomosed to the cecum. All feeding attempts failed, and the infant
      suffered from malabsorption. Calories and proteins had to be supplied by
      intravenous total parenteral nutrition. At 3 months of age there was significant
      widening of the remaining bowel and Bianchi's bowel-lengthening procedure was
      performed. The postoperative course was uneventful and there was gradual
      improvement in intestinal absorptive capacity. The patient was weaned from
      parenteral nutrition at 3 years of age. Now, 2 years later, she eats a normal
      diet.

PMID- 10911486
TI  - [Radiologic appearance of "falling gallstones" during laparoscopic
      cholecystectomy].
AB  - Laparoscopic cholecystectomy is the "gold standard" in treating cholelithiasis.
      Stones are frequently lost in the peritoneal cavity during the procedure, but
      "missing stones" have been regarded as insignificant. However, there is
      accumulating evidence that untreated "lost" stones may cause complications even
      years after operation. We present a 65-year-old woman who presented with vague
      complaints, anemia and an elevated ESR. CT scan showed an infiltrating process in
      extra-abdominal muscles compatible with sarcoma. At operation, 2.5 years after
      previous laparoscopic cholecystectomy, an abscess was found which contained
      biliary stones. Because of their small size they were not visible on CT scan. We
      discuss the possible ways of handling "falling stones."

PMID- 10911487
TI  - [Investigating chest pain--is there a gender bias?].
AB  - Ischemic heart disease (IHD) is women is characterized by a higher morbidity and
      mortality in the peri-infarction and coronary bypass peri-operative periods.
      These epidemiological data strengthen our impression that the health system
      unintentionally "ignores" the high proportion of females with IHD. The process of
      investigating chest pain, diagnosing IHD, and the subsequent treatment and
      rehabilitation, seem to differ between the genders. Time elapsed from beginning
      of chest pain to diagnosis of IHD seems to be longer in women than in men.
      Personal, educational and social factors are contributory. Although time elapsed
      between diagnosis and rehabilitation is usually similar in the genders, peri
      operative morbidity and mortality are higher in women. It may be that the higher
      rates in women are caused by delay in diagnosis and treatment, which allows
      worsening of the disease in women before treatment. This delay can occur during
      the time needed for evaluation of chest pain, from the door of the physician to
      diagnosis and treatment. In our retrospective study we determined the difference
      in referral of men and women with chest pain to the emergency department (ED) and
      the attitude of physicians in the ED and medical department to chest pain in men
      and in women, including final diagnosis on discharge. 615 patients over 18 years
      referred to the ED for chest pain during 3 randomly chosen, consecutive months
      were studied. We found that women constituted only 39.5% of the referred
      patients, but the proportion hospitalized was similar to that in men.
      Hospitalized women were older (57.7 +/- 18.4 versus 49.7 +/- 17.8 years in men),
      and had more risk factors (4 versus 2 in men). Proportions of specific diagnoses
      on discharge from hospital were equal in the genders. To bridge the differences
      and to implement education in prevention, investigation and treatment of IHD in
      women, we established the "Female Heart" clinic. The objective of this clinic is
      to reduce differences in the first step, in the process of evaluating chest pain
      in women, by educating and encouraging them to present early to their physicians,
      and by changing physicians' attitudes in the investigation of chest pain in
      women. We plan to determine in a prospective study if these goals are reached.

PMID- 10911488
TI  - [Postoperative pain relief].
AB  - The traditional approach to postoperative pain relief (POPR) is still in effect
      in many surgical departments in Israel: morphine or meperidine given i.m. "on
      demand." In spite of the availability of modern and more effective approaches for
      POPR, their utilization in hospitals in Israel is lagging. The aim of this
      project was to study how POPR is being performed in a randomly chosen academic
      gynecological department, with the assumption that increased awareness will
      facilitate the necessary changes needed to improve POPR. Four aspects of POPR
      were studied in 60 female subjects who underwent elective hysterectomy: patients'
      attitudes to postoperative pain and its relief ascertained prior to surgery;
      analgesics, prescribed and delivered; assessment of postoperative pain; and
      patients' satisfaction with POPR. Results show that patients' fear of
      postoperative pain is the largest component of their overall fear of the surgical
      procedure. Although they anticipate intense pain, and expect significant POPR,
      most women prefer not to receive opioid analgesics. Most patients received an
      average of 10-20 mg of morphine during the first 2 postoperative days. They
      reported at least moderate to severe pain on 5 of 6 measurements during that
      period. Nevertheless, most patients were satisfied with their POPR. It is likely
      that patients expressed a high level of satisfaction primarily due to their low
      level of expectations. Assuming that these results represent the POPR situation
      nationwide, practical steps should be undertaken for its improvement.

PMID- 10911489
TI  - [Warning labels on medications--influence of warning labels and physicians'
      orders on patient behavior].
AB  - Compliance of 40 mothers with a warning label, "for external use," on a medicine
      package was checked in a survey in a primary care clinic for children. We also
      checked parents' attitudes to giving a medicine to their child when instructions
      given by the physician or by a friend contradicted the printed warning on the
      label. All mothers who were told that the medicine was recommended by their
      physicians accepted the recommendation without hesitation. Another group included
      20 mothers who were told that the medicine was recommended by a friend. 9 of 20
      mothers in this group refused to use the medicine. Talking with the nurse about
      the potential risk of medicine in general, some mothers, after second thought,
      refused to give the medicine to their child. At the end, 65% of recommendations
      made by a friend were rejected by mothers as compared to only 15% of the
      physicians' recommendations. 35 of 40 mothers (87%) understood the meaning of the
      warning label, but only 13 (32%) had noticed it at all. We conclude that patients
      may accept their physicians' recommendation to use a medicine despite a
      contradictory warning label much more readily than when it was recommended by a
      friend. Therefore, any intervention program intended to promote a more cautious
      use of medicines should include not only the explanations of the various warning
      labels but should also promote a change in the patient's behavior to a more
      active search for warning labels.

PMID- 10911490
TI  - [Comparison between every-day and every-3-days fluoxetine in young, moderately
      depressed out-patients].
AB  - Fluoxetine is now a well-known and often-used specific serotonin reuptake
      inhibitor (SSRI) and antidepressant. It has a very long active half-life, from 2
      16 days. Our hypothesis was that sufficient therapeutic effectiveness would be
      achieved by prescribing the drug less frequently than once a day. To establish
      whether there is a difference between fluoxetine given daily or every 3 days, we
      assigned 25 outpatients with mild to moderate, acute major depressions (DSM-IV)
      to receive fluoxetine (20 mg), either each day or every 3 days. The study was
      open-labelled, using for assessment the HAM-D, GHQ-28 side-effect checklist and
      clinical judgment questionnaires. Follow-up lasted 6 months. Results indicated no
      differences in the clinical outcomes, except for slightly fewer side-effects in
      the study group. Although the open label design limits drawing definitive
      conclusions, our preliminary results provide more information, and support our
      hypothesis that low-dosage fluoxetine is beneficial. However, more comprehensive,
      double-blind studies are necessary to confirm our preliminary results.

PMID- 10911492
TI  - [The therapeutic orphan--end of an era?].

PMID- 10911491
TI  - [Tiagabine--a new antiepileptic drug].

PMID- 10911494
TI  - [The epidemiology of disasters].

PMID- 10911493
TI  - [Cloning in humans--state of the art].

PMID- 10911495
TI  - [Athlete's heart, or: where is the cut-off point between a healthy adaptive
      response and heart disease? Part I].

PMID- 10911496
TI  - [Imaging in liver transplantation--the 35-year revolution].

PMID- 10911497
TI  - [The "open artery hypothesis" following myocardial infarction-- catheterization
      for everyone?].

PMID- 10911498
TI  - [Myositis ossificans].

PMID- 10911499
TI  - [On the connection between psychological stress and diabetes mellitus].

PMID- 10911500
TI  - [Compliance with treatment of low back pain].

PMID- 10911501
TI  - [Nitric oxide in pregnancy].

PMID- 10911502
TI  - [Development of new drugs--the United States regulatory perspective, 1998].

PMID- 10911503
TI  - [External fixation of pelvic fractures--considerations and indications].

PMID- 10911504
TI  - [Soroka Medical Center].

PMID- 10911505
TI  - Reports stress need for global perspective on TB control.

PMID- 10911507
TI  - Growth of highly integrated health systems continues.

PMID- 10911506
TI  - NHLBI advocates closer attention to systolic blood pressure.

PMID- 10911508
TI  - Texas fight over drug product selection ends.

PMID- 10911510
TI  - Reaching out to pharmacy technicians.

PMID- 10911509
TI  - Turmeric.

PMID- 10911511
TI  - Medication assistance programs for uninsured and indigent patients.
AB  - Pharmaceutical company-sponsored medication assistance programs and the
      pharmacist's role in obtaining medications for indigent patients are discussed.
      Information about enrolling in medication assistance programs can be obtained
      through a variety of sources, including the Internet. Although some eligibility
      criteria may be common to many programs, each company operates independently, and
      the eligibility criteria vary, individuals involved in the administration of
      medication assistance programs should strive to ensure that correct information
      is reported. Pharmacists can play an important role in acquiring medications for
      patients by reviewing patient information, recommending patients for enrollment,
      and serving as a liaison between the patient or health care provider and the
      program administrator. Many pharmaceutical companies have programs that provide
      prescription medications to indigent or uninsured patients. Pharmacists can serve
      as a liaison between these programs and the patient or the health care provider.

PMID- 10911512
TI  - Absence of an interaction between ibuprofen and zaleplon.
AB  - The potential interaction between zaleplon and ibuprofen was studied. Healthy
      adult volunteers were given a dose of zaleplon 10 mg alone, a dose of ibuprofen
      600 mg alone, or a dose of zaleplon 10 mg and a dose of ibuprofen 600 mg
      concomitantly in an open-label, randomized, three-period crossover study. There
      was a seven-day washout period between treatments. Venous blood samples were
      collected for pharmacokinetic analysis at various intervals up to 14 hours after
      drug administration. A total of 17 subjects (11 men and 6 women) completed the
      study. There were no significant differences between zaleplon monotherapy and
      combination therapy in mean +/- SD, of zaleplon clearance (CL) (2.80 +/- 0.72
      versus 2.72 +/- 0.89 L/hr/kg, respectively), maximum plasma concentration (Cmax)
      (37.1 +/- 17.9 versus 39.8 +/- 20.0 ng/mL), or area under the concentration
      versus-time curve (AUC) (56.7 +/- 22.8 versus 59.2 +/- 22.0 ng.hr/mL). There were
      no significant differences between ibuprofen monotherapy and combination therapy
      in ibuprofen CL (71.6 +/- 17.0 versus 71.7 +/- 14.9 L/hr/kg), Cmax (40.8 +/- 10.2
      versus 40.4 +/- 10.0 micrograms/mL), or AUC (127.6 +/- 29.6 versus 126.4 +/- 29.7
      micrograms.hr/mL). Three subjects had one or more adverse effects with zaleplon
      alone, one subject had one or more with ibuprofen alone, and one subject had one
      or more with combination therapy. The adverse effects were mild and resolved
      without intervention. There was no evidence of a significant interaction between
      zaleplon and ibuprofen.

PMID- 10911513
TI  - Stability of propylthiouracil in extemporaneously prepared oral suspensions at 4
      and 25 degrees C.
AB  - The stability of propylthiouracil in two extemporaneously prepared suspensions at
      4 and 25 degrees C was studied. Commercially available 50-mg propylthiouracil
      tablets were used to prepare suspensions in 1:1 Ora-Sweet:Ora-Plus and in 1:1 1%
      methylcellulose:Simple Syrup, NF, to yield a propylthiouracil concentration of 5
      mg/mL. Each suspension was stored in 10 amber plastic prescription bottles, 5 of
      them at 4 degrees C and the other 5 at 25 degrees C. Three samples were taken
      from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days for assay by stability
      indicating high-performance liquid chromatography. More than 90% of the initial
      propylthiouracil concentration was retained in both suspensions for 70 days at 25
      degrees C and for 91 days at 4 degrees C. There were no changes in physical
      appearance, color, or odor, and the pH remained essentially unchanged.
      Propylthiouracil 5 mg/mL in two extemporaneously prepared oral suspensions was
      stable for at least 70 days at 25 degrees C and for at least 91 days at 4 degrees
      C.

PMID- 10911514
TI  - Effect of sex on serum protein binding characteristics of phenytoin in pediatric
      patients with epilepsy.

PMID- 10911515
TI  - Reducing costs through centralization and standardization of an i.v. admixture
      program.

PMID- 10911516
TI  - ASHP guidelines on quality assurance for pharmacy-prepared sterile products.
      American Society of Health System Pharmacists.

PMID- 10911518
TI  - Slow down--errors ahead.

PMID- 10911517
TI  - Pharmacists and the quality-of-care imperative.

PMID- 10911519
TI  - Pharmaceutical and antimicrobial differences between propofol emulsion products.

PMID- 10911520
TI  - Pancrelipase for treatment-refractory diarrhea associated with nelfinavir.

PMID- 10911521
TI  - Removal of drug samples from two teaching institutions.

PMID- 10911522
TI  - Recovery of fosphenytoin injection after simulated nasogastric administration.

PMID- 10911523
TI  - [What are the implications of office pediatricians managing outpatient
      emergencies?].

PMID- 10911524
TI  - [A normal sweat test does not exclude the diagnosis of cystic fibrosis].

PMID- 10911526
TI  - [Evaluation of the quality of life of infants and very young children: validation
      of a questionnaire. Multicenter European study].
AB  - In the last few years, evaluating quality of life in children has become possible
      using specific instruments; nevertheless, there is still an unsolved issue
      concerning the earliest ages, when the child is not able to give his/her own
      opinion. QUALIN, a new instrument designed to assess an infant's quality of life
      (between the ages of three months and three years) was developed from the study
      of spontaneous criteria used by parents or caregivers (paediatricians or nurses)
      when they think about the quality of life of a baby (preliminary survey including
      800 open-ended questionnaires). PATIENTS AND METHODS: One thousand four hundred
      and twelve children under the age of three were included in this validation
      study. QUALIN questionnaire is a 34-item scale and can be completed by parents or
      caregivers. Two forms are available: one form is designed for children under the
      age of one and the other is designed for children between the ages of one and
      three. The QUALIN questionnaire was translated into English, Italian and Spanish,
      and a European multicentric validation study was conducted in Belgium, France,
      Italy, Luxembourg, Spain and Switzerland. Data were collected with QUALIN
      questionnaires from children's parents and paediatricians. RESULTS: The
      psychometric properties of the scale are satisfactory (acceptability 90%,
      Cronbach's coefficient alpha over 0.75, correlations between two raters over
      0.50, construct validity with principal component analysis showed emerging
      factors in agreement with the hypotheses linked to the questionnaire
      construction). The results are interesting, showing significant differences
      according to the health status of the children and their country of origin.
      CONCLUSION: The QUALIN questionnaire can be used for studies concerning the
      quality of life of children less than three years of age.

PMID- 10911525
TI  - [Mucopolysaccharidosis type I in Morocco: clinical features and genetic profile].
AB  - BACKGROUND: Mucopolysaccharidoses (MPS) are inherited metabolic disorders due to
      lysosomal enzyme deficiencies, leading to glycosaminoglycan accumulation in
      lysosomes of different tissues. The aim of this study was to characterize MPS
      types, particularly MPS I, which are difficult to differentiate by clinical
      features. PATIENTS AND METHODS: Over a period of three years (June 1996-May
      1999), 16 Moroccan patients (3-20 years old) with MPS were investigated. Twelve
      of them came from the Souss region. In subjects with suspected clinical MPS I or
      II, the diagnosis was confirmed by biochemical investigations, which included the
      quantification of total glycosaminoglycans (GAGs) released in urine, their
      identification, and the assay of alpha-L-iduronidase activity in leucocytes. A
      molecular analysis was performed in parallel, to provide the genetic proof of the
      diagnosis. RESULTS: These 16 patients belonged to 12 families, nine of which were
      consanguineous (75%). Twelve patients had Hurler syndrome and three had
      Hurler/Scheie's syndrome; no case of Scheie's syndrome was observed. Short
      stature, coarse face, organomegaly, hernia, cardiac disease, mental delay and
      dysostosis were observed in variable degrees. We report three cases without
      corneal clouding. Increased total urinary GAGs, identified as dermatan sulfate
      and heparan sulfate by thin-layer chromatography and total deficiency of alpha-L
      iduronidase activity, were noted in studied subjects. At the molecular level the
      P533R mutation was detected in 24 among 26 alleles studied. CONCLUSION: It is now
      possible to perform the screening of MPS I and II in Morocco by analysis of
      clinical, radiologic observations and biological investigation. The predominance
      of P533R mutation could permit the screening of healthy heterozygotes and genetic
      counselling for families of Moroccan descent.

PMID- 10911527
TI  - [The impact on families of sickle cell disease in Togo].
AB  - AIM: In order to master the difficulties due to sickle cell disease, this work
      aimed at assessing the effects on the families of the presence of a child with
      sickle cell disease in Togo. POPULATION AND METHODS: From April 1 to November 31,
      1998, 103 families with one or many sickle cell patients followed up in the
      Sickle Cell Care Unit of the pediatric department of the Lome Teaching Hospital
      were surveyed. Main care takers of patients with sickle cell disease, especially
      mothers (90.3% of cases), were surveyed. RESULTS: Many parents were disturbed;
      the most common troubles were: compassion (pity) toward the child, 92.2%;
      insomnia, 82.5%; frustration, 76.7%; and fear of the death of the child, 73.5%.
      Less educated parents and those who lived alone (single parents, widows,
      separated) were more affected. Sickle cell disease caused the separation of seven
      couples out of 26 (26.9%), while in 11 couples of the 63 who still live together,
      relationships had deteriorated (17.5%). Most of the parents (83.3%) exaggerated
      the protection of their child and 65% mentioned financial problems. CONCLUSION:
      There is no doubt about the unfortunate effects of the presence of children with
      sickle cell disease in a family in Lome. Many joint actions should be taken
      toward the sick children and their families in order to reduce their sufferings.

PMID- 10911529
TI  - [Self-healing Hashimoto-Pritzker histiocytosis].
AB  - Congenital 'self-healing' Langerhans' cell histiocytosis of Hashimoto-Pritzker is
      a rare disease occurring mainly in the neonatal period. CASE REPORT: We report on
      the case of a newborn with widespread eruption since birth, consisting of
      nodules, papulonodules, sometimes with ulcerations and scabs, concerning all the
      body, with a predilection for the cephalic area and the scalp, without general
      abnormalities. The clinical examination, histopathological data,
      immunohistochemistry, and the benign evolution in nine-, 18- and 24-month periods
      without particular treatment define the diagnosis of congenital self-healing
      Langerhans' cell histiocytosis of Hashimoto-Pritzker. CONCLUSION: The position of
      this disease among the Langherans' cell histiocytoses is probably situated at the
      benign pole. This is a benign self-healing disease restricted to the skin and the
      prognosis is good (self-involution). It is important to eliminate a malignant
      form of other Langerhans' cell histiocytosis such as Letterer-Siwe disease by a
      checkup searching for a visceral disease. The good prognosis should not lead to
      forget the possibility of error or forms of relapses; it is therefore imperative
      to have a rigorous, regular and especially long-term follow-up.

PMID- 10911528
TI  - [Opsoclonus-myoclonus syndrome associated with non-metastatic neuroblastoma. Long
      term survival. Study of the French Society of Pediatric Oncologists].
AB  - Opsoclonus-myoclonus is a rare syndrome characterized by multidirectional chaotic
      eye movements, myoclonus and ataxia. In children, it could be a paraneoplastic
      syndrome in association with neuroblastoma, usually with a high survival rate,
      but having a high frequency of neurologic and psychologic sequelae. OBJECTIVES:
      The aim of this study was to describe oncologic outcome (prospectively) and
      neurologic outcome (retrospectively) in children with non-metastatic
      neuroblastoma, and to determine its best treatment. PATIENTS AND METHODS: Data
      were collected on 21 children diagnosed with localized neuroblastoma and
      opsoclonus-myoclonus between 1990-1999 from the French Society of Pediatric
      Oncology institutions. RESULTS: Median age at diagnosis was 18 months. Location
      of the tumor was abdominal in 14 cases, thoracic in three cases, pelvic in three
      cases, and cervical in the last case. There was a majority of small tumors with a
      maximal diameter < 5 cm in 13 cases. Only four tumors were initially considered
      as unresectable tumors and received first-line chemotherapy. Complete macroscopic
      resection was performed in 20 cases (four after primary chemotherapy). Nine
      children received chemotherapy. Twenty children remained in first complete
      remission, and one relapsed and died (the unique NMYC amplified case). Treatment
      for opsoclonus-myoclonus varied widely. Only one child received no medical
      treatment for opsoclonus-myoclonus, because of complete resolution of neurologic
      symptoms after exclusive surgery. The following agents were used: corticosteroids
      in 18 cases, intravenously immune globulin in five cases, and antiepileptic drugs
      in seven cases. Ten patients experienced relapses of opsoclonus-myoclonus
      symptoms, mainly related to the decrease of steroid therapy (5/10). Ten of 16
      assessable children had persistent neurologic deficits including speech delay or
      cognitive deficits (8/16), ataxia (6/16), motor delay (2/16), and behavioral
      problems (2/16). There is no correlation between neurologic outcome, and either
      age at diagnosis or duration of neurologic symptoms, or type of treatment of the
      tumor, particularly chemotherapy. CONCLUSION: Persistent neurologic deficits are
      characteristic for children with neuroblastoma and opsoclonus-myoclonus.
      Neurologic outcome seems unrelated to the treatment of neuroblastoma, which
      should exclusively be conducted according to oncological criteria. The treatment
      of opsoclonus-myoclonus should be standardized, mainly based on high-dose
      hydrocortisone, with a very low decreasing dosage, associated to intravenously
      immune globulin in severe cases. A biological immunologic work-up of the disease
      and cautious neurologic and psychologic standardized follow-up should be
      performed.

PMID- 10911530
TI  - [Digitalis intoxication during the neonatal period: role of dehydration].
AB  - BACKGROUND: Despite the great progress which has been made in the treatment of
      acute digitalis intoxication by digoxin-immune Fab, it still remains a severe
      complication of cardiotonic therapy. CASE REPORT: A neonate with ventricular
      septal defect and large left-to-right shunt was treated with digitalis and
      diuretics at the usual starting doses. An intensive phototherapy was also
      required because of a hyperbilirubinemia due to glucose-6-phosphate dehydrogenase
      deficiency. Toxic digoxin accumulation (plasma level 14 ng/mL) was diagnosed
      three days after the initiation of treatment by the presence of sinus bradycardia
      and bursts of ventricular fibrillation. Intravenous administration of digoxin
      specific antibody Fab fragments (Digidot) was effective, with a rapid improvement
      of the digitalis poisoning. CONCLUSION: Because of the particularities concerning
      drug distribution, metabolism and elimination of drugs in the neonatal period,
      the digoxin therapeutic index is narrow. This case report suggests the
      involvement of phototherapy and diuretics, which might induce a significant
      decrease in extracellular water and drug distribution volumes, ultimately
      promoting the occurrence of an intoxication.

PMID- 10911531
TI  - [Feingold syndrome].
AB  - BACKGROUND: Feingold syndrome is a combination of hand and foot anomalies,
      microcephaly, tracheo-esophageal fistula, esophageal/duodenal atresia, short
      palpebral fissures and developmental delay. The most frequent physical findings
      are clinodactyly of the second and fifth fingers with absent or hypoplastic
      middle phalanges, and syndactyly of the toes. Inheritance is autosomal dominant
      (MIM number 164280) with full penetrance concerning hand anomalies, variable
      expressivity and great intrafamilial variability. CASE REPORT: We report the case
      of an African boy with duodenal atresia, microcephaly, brachymesophalangy of the
      second and fifth fingers, unilateral thumb hypoplasia, bilateral syndactyly of
      toes 2-3 and amesophalangy of the toes. Karyotype was normal. No other member of
      the family was affected. A fresh mutation is possible. CONCLUSION:
      Brachymesophalangy affecting mainly the second and fifth fingers and
      amesophalangy of the lateral toes are cardinal clinical findings in Feingold
      syndrome. These clinical findings define the syndrome of brachydactyly A4-Temtamy
      type (MIM 112800), suggesting that brachydactyly A4 would be a partially
      expressed Feingold syndrome. The incidence of esophageal/duodenal atresia is 29%,
      including all the known cases. All karyotypes of reported patients were normal.

PMID- 10911532
TI  - [Constitutional deficiency of pulmonary surfactant protein B: clinical
      presentation, histologic and molecular diagnosis].
AB  - We report a female full-term infant with fatal respiratory failure of early onset
      due to inherited SP-B deficiency. Lung biopsy was performed at 18 days after
      birth, with histopathological characterization indicating congenital alveolar
      proteinosis. Immunohistochemical studies of lung tissue revealed the absence of
      SP-B and the presence of intra-alveolar SP-A normal quantities. Analysis of
      genomic DNA showed homozygosity for the 121ins2 mutation of the SFTPB gene. The
      infant died 21 days after birth. Both parents were heterozygotes for the
      mutation. Chorionic villus sampling was performed at the first trimester of the
      following pregnancy. Restriction analysis of amplified fetal DNA, studies of
      microsatellite segregation and direct sequencing led to the diagnosis of
      homozygosity for the parental wild-type allele. The diagnosis of congenital SP-B
      deficiency should be suspected whenever an early and acute respiratory failure in
      a term or near-term infant does not resolve after five days of age: diagnostic
      confirmation can be easily and rapidly obtained with the analysis of genomic DNA
      and immunohistochemical characterization of lung tissue.

PMID- 10911534
TI  - [Radiologic case of the month. Fracture-dislocation of the humeral epiphysis
      removed from obstetrical origin].

PMID- 10911533
TI  - [Antibiotic therapy in cystic fibrosis. II Antibiotic strategy].
AB  - Antibiotherapy is one of the main treatments of cystic fibrosis, contributing to
      a better nutritional and respiratory status and a prolonged survival. The choice
      of antibiotics depends on quantitative and qualitative analysis of sputum,
      bacteria resistance phenotypes and severity of infection. Haemophilus influenzae
      infection can be treated orally with the association of amoxicillin-clavulanic
      acid or a cephalosporin. Staphylococcus aureus generally remains sensitive to
      usual antibiotics; in case of a methicillin-resistant strain, an oral bitherapy
      or a parenteral cure can be proposed. Treatment of Pseudomonas aeruginosa is
      different in case of first colonization or chronic infection: in first
      colonization, parenteral antibiotherapy (beta-lactams-aminoglycosids) followed by
      inhaled antibiotherapy may eradicate the bacteria; in chronic infections,
      exacerbations require parenteral bi-antibiotherapy (beta-lactams or quinolons and
      aminoglycosids) for 15 to 21 days, inhaled antibiotics between the cures being
      useful to decrease the number of exacerbation. A careful monitoring of
      antibiotherapy is necessary because of possible induction of bacterial
      resistance, nephrotoxicity and ototoxicity of aminosids and allergy to beta
      lactams.

PMID- 10911535
TI  - [Suicidal behavior in adolescents. What questions for the professional?].
AB  - Suicidal behaviors are a major public health concern, particularly among
      adolescents. Yet health care providers are often ill-prepared in dealing with at
      risk adolescents, and particularly uncomfortable with the issue of suicide. By
      means of ten simple questions, the author tries to address some of the common
      queries of primary health care providers, hoping to increase their understanding
      of the phenomenon and their skills in detection, guidance and prevention.

PMID- 10911536
TI  - [Photodermatosis and photoprotection in children].
AB  - Photodermatosis is an heterogeneous group of affections characterized by an
      abnormal sensitivity of skin to sunlight responsible of a local or generalized
      eruption. Rare in children, the most frequent of them such as sun-burns,
      phytophotodermatosis and phototoxicity are fortunately benign, brief and
      spontaneously resolving. Some of them disappear spontaneously after few years
      like polymorphic light eruptions which are rather observed in children older than
      ten years. In case of recurrence, rare diagnosis have to be investigated with
      specific tests (phototests, blood exams, genetic investigations) as some
      metabolic or genetic disorders may be revealed by a photosensitivity, especially
      before the age of three years. The questioning of the parents and of the child is
      fundamental. Many diagnosis may be discussed depending on age and circumstances.
      Treatment consists in photoprotection recommendations, solar eviction and regular
      application of protective screens, whose spectrum of protection are different and
      have to be known in order to prescribe an adapted photoprotection.

PMID- 10911537
TI  - [Co-sleeping and sudden infant death syndrome].
AB  - Bedsharing has recently become a controversial subject. Some authors, mainly from
      North America, assign to bedsharing a positive effect on the efficacy and
      duration of breast-feeding. Moreover, it would protect against sudden infant
      death syndrome (SIDS). Conversely, other studies consider bedsharing as an
      additional risk factor for SIDS. From the literature data, there is some evidence
      for an increased risk of SIDS when bedsharing is associated with maternal smoking
      and alcohol consumption. Bedsharing cannot be recommended as an absolutely safe
      practice. Breast-feeding mothers should be aware of these potential hazards.

PMID- 10911538
TI  - [AIDS in Africa, considered as a disease of civilization].

PMID- 10911539
TI  - [Do standard safety seats for young children protect against head injury in urban
      traffic accidents?].

PMID- 10911540
TI  - [Umbilical hernia in African black children. the danger of progression].

PMID- 10911542
TI  - [National French observation study of ceftriaxone treatment of acute
      pyelonephritis in children].

PMID- 10911541
TI  - [Controversies about acute otitis media].

PMID- 10911543
TI  - [Our experience with portable insulin pumps in young children].

PMID- 10911544
TI  - [Regarding the nutritional status of African children adopted in France].

PMID- 10911545
TI  - [The commissions' life. The Commissions of the French Society of Pediatrics].

PMID- 10911546
TI  - [Point of view. Pediatrics and school troubles].

PMID- 10911547
TI  - [Genetics. Genetic tests in children. An immediate reflexion is needed].

PMID- 10911549
TI  - Deconstructing Mendel: new paradigms in genetic mechanisms.
AB  - As knowledge of the mechanisms of genetic action expands, this new information
      must be incorporated into the whole. The result is that old concepts are modified
      or deleted or new paradigms are created. The authors review advances in the
      understanding of traditional and nontraditional inheritance, including genomic
      imprinting and mitochondrial inheritance.

PMID- 10911548
TI  - Guidelines for the diagnosis and treatment of acromegaly: a Canadian perspective.
AB  - Acromegaly is a chronic, debilitating condition caused by excessive secretion of
      growth hormone (GH). In the majority of cases the condition results from benign
      pituitary adenomas or, rarely, from ectopic production of GH-releasing hormone.
      Regardless of the cause, excess GH results in physical disfigurement associated
      with arthropathy, diabetes, hypertension, cardiac dysfunction, obstructive sleep
      apnea and colonic neoplasia. The death rate for acromegalic patients is 2 to 3
      times higher than that of the general population, but with appropriate reduction
      of GH hypersecretion it tends to shift into the normal range. Treatment is thus
      aimed at normalizing GH secretion; eradicating or stabilizing the pituitary
      tumour while preserving normal pituitary function, and managing the associated
      complications. The treatment modalities available to achieve these objectives
      include transsphenoidal surgery, pharmacotherapy and radiation, or various
      combinations of these. This review provides an update on our current
      understanding of the pathophysiology of GH hypersecretion in acromegaly, the
      newly defined diagnostic criteria and the end point for a cure for acromegaly,
      and on new developments in drug treatment with the advent of slow-release forms
      of somatostatin analogues and the longer-acting dopamine receptor agonists, as
      well as in the area of radiotherapy. Its main purpose is to guide any physician
      involved in the diagnosis and management of patients with acromegaly.

PMID- 10911550
TI  - Multidimensional evaluation of training offered by the Finnish Institute of
      Occupational Health (FIOH).
AB  - This paper is about an evaluation of training offered by the Finnish Institute of
      Occupational Health (FIOH). FIOH is a research organisation, which produces,
      collects and disseminates information about work and health and promotes the
      utilisation of this knowledge. The target groups of the training are occupational
      health physicians, occupational health nurses, occupational health
      physiotherapists, safety officers and other personnel responsible for the
      development of the working environment. The central aim of the Evaluation Group
      was to evaluate the quality of the training given at FIOH and to make
      recommendations for further development in the near future. The evaluation was
      done by a joint evaluation group. The Evaluation Group consisted of specialists
      working in the field of occupational health and safety and in adult education
      outside the Institute, as well as staff members from the Institute. The specific
      objectives were: to evaluate how the objectives of the training were set and how
      the training was arranged to meet the needs of society: how relevant the training
      topics were from the viewpoint of the clients; how the annual planning of the
      training programme was done; and whether the courses were carried out in such a
      way that they would have a practical impact. All the evaluation should support
      the development and assessment skills of the training given by FIOH. Both the
      relevance of the training was assessed at the level of the society and at the
      level of training courses. The supply of the training was evaluated by different
      stakeholders. The quality of the training courses was evaluated by specialists in
      pedagogics and adult education. They evaluated the planning of the courses, the
      contents of the courses and teaching methods used at the courses, the course
      materials and the evaluation practices. The presentation describes the use of the
      multidimensional, process and participation oriented evaluation model and the
      outcomes of the evaluation.

PMID- 10911551
TI  - [The use of Internet in occupational medicine and industrial hygiene].
AB  - The internet as we know is today includes an array of tools that make information
      exchange easier than ever before. The best known Internet tools are the World
      Wide Web and the electronic mail. In the present job we identify those that are
      the home pages that better can help Industrial Hygienists and Doctors to acquire
      useful information for the profession. From the detailed examination of the
      possibilities offered from Internet (web documents acquisition, reading on line
      of scientific papers, use of mailing lists and e-mail) we can wait in future that
      the this new instrument will play an important role by offering extensive
      knowledge and information in the field of occupational and environmental health.

PMID- 10911552
TI  - [Occupational vascular acrosyndromes. Considerations on plethysmographic changes
      in the fingers resulting from postural variations of the arms: do they have
      diagnostic relevance or just physiopathologic significance?].
AB  - 334 subjects all with anamnesis indicating a vascular acrosyndrome (mostly due to
      their working conditions) were studied using the pulsoplethysmographic method to
      evaluate whether a relationship exists between the absence of increases to
      physiological acral posture and the presence of Raynaud's disease successively
      induced by Cold Test. The results obtained showed marked correlation (which for
      some of the subgroups examined was also statistically significant) between the
      lack of postural regolation and abnormal or frankly phatological plethysmographic
      findings following the Cold Test. The results appeared to be of some relevance in
      the physiopathologic interpretation of vascular acrosyndromes. According to the
      authors, the findings constitutive further proof of the reole played by changes
      in the "balance of vessel motility" in maintaining district circulatory
      homeostasis and may indicate the prevalence of vasoconstriction over endotelially
      mediated vasodilation. Consequently, the adoption of a routine test to evaluate
      postural sphygmic changes, before the traditional Cold Test, would allow more
      precise diagnosis and prognosis, particularly in the area of professional
      angiopathies.

PMID- 10911553
TI  - [Proposal of a computerized system for chemical risk management at biomedical
      laboratories].
AB  - The current italian and european directives require as an essential part of
      preventive procedures the risk assessment in every work setting. This procedure
      may be however difficult to be applied because of variability and specificity of
      work environment, work organisation, chemicals ect. It is true for the biomedical
      laboratories when the attention is focused on the identification and exposure
      evaluation of chemicals related to the analytical process, i.e. the first step to
      reach an accurated risk assessment. The starting point often has been the list of
      theoretically used compounds, which could be not exhaustive, or they could not
      reflect type and amount of chemicals really used. The proposed system is directly
      managed by the laboratory workers, by an labeling and reading bare code system.
      By the software, information about type, location, storage of the compounds
      present in the laboratory and amount used by each laboratory worker (by a
      personal card) are easily available. The proposed system should ensure precision
      and method in recording type and amount and in approximating the contact-
      absorption of the compounds used by each operator. By improving the chemical
      exposure assessment, a more accurate health and epidemiological surveillance
      would be possible. Finally, the system, by enabling the management of purchase,
      storage, utilization, waste of chemicals, could become an useful device for the
      quality assurance procedures.

PMID- 10911554
TI  - [Spinal diseases in the health setting. Epidemiologic findings at a hospital in
      eastern Sicily].
AB  - The importance of spinal column disorders has long been known, both for their
      frequency in working environments and the social consequences they provoke, i.e.
      absence from work and social insurance costs. Our study focussed on 800 health
      care workers: nursing personnel who provide direct patient care, and 150 office
      workers of Sicily Hospital. We estimated column pathologies by using Colombini,
      Occhipinti, Grieco method. On the basis of our results we may affirm that the
      column disorders are more frequent in hospital assistants: S.A.P. II degree 22%
      S.A.P. III degree 10%, in office workers S.A.P. II degree 6% S.A.P. III degree
      3%.

PMID- 10911555
TI  - Iodine deficiency and increased risk from radioactive iodine intake in nuclear
      medicine personnel.
AB  - Since the entity of the stable endogenous iodine pool is inversely related to the
      probability of thyroid uptake of radioactive iodine isotopes in subjects exposed
      for professional reasons to radioiodine intake, we evaluated the urinary iodine
      excretion, which is a reliable indicator of stable iodine daily intake, in 19
      subjects of a nuclear medicine department. Seventeen out of 19 subjects showed a
      reduced iodine elimination < 150 mcg iodine per g of urinary creatinine, while
      the values of TSH and free fractions of T3 e T4 were within normal limits.
      Thyroglobulin levels were increased in 5 subjects only, all with reduced iodine
      excretion. Iodine deficiency is still present in several european areas and is
      responsible for several thyroid diseases including cancer; it is also responsible
      for increased thyroid dosimetry after accidental intake. According to Breuer, an
      increased radiation rate to bone marrow and ovaries is expected in subjects with
      a reduced endogenous iodine pool. On account of these results, we recommend to
      monitor the urinary iodine excretion in personnel exposed to the risk of
      radioiodine contamination and correct their dietary daily intake, thus reducing
      organ dosimetry not only in normal working conditions, but also in case of
      accidental internal contamination.

PMID- 10911556
TI  - [Sleep disordered breathing: a new risk factor for accidents].
AB  - An estimated 2%-4% of the working population could be affected by sleep
      disordered breathing, in particular by obstructive sleep apnea syndrome. The main
      symptom is excessive daytime sleepiness, caused by sleep interruptions induced by
      respiratory events. The level of sleepiness varies according to the severity and
      duration of the disease: from a slight decrease in vigilance to an almost total
      inability to keep alert for more than a few hours. In addition, there is an
      increase in cardiovascular risks and dysmetabolic disorders, which has a variable
      incidence in the affected population. Even less severe clinical conditions can
      lead to a reduction in the power of concentration, attention and working
      performance. The recent trend of research aims at verifying the association
      between risk factors and obstructive sleep apnea syndrome in order to identify
      those subjects at real risk, to determine the actual level of sleep-disordered
      breathing which should be treated and whether the less serious disturbances, so
      frequent in the general population, represent a real threat to health.

PMID- 10911557
TI  - [Ethical problems in health surveillance].
AB  - Surveillance of workers' health in the field of occupational medicine poses
      substantial ethical problems in view of occupational medicine's complex
      responsibilities towards workers and employers, preventive and protection
      services, workers' representatives, public healthcare and preventive medicine
      facilities, controlling agencies and judicial authorities. Potentially
      conflicting rights and duties often come into play in this sector. In the last
      few years various international and national bodies have drawn up codes of ethics
      or guidelines for the conduct of physicians in occupational medicine, three of
      which are of particular importance: 1) The International Ethical Code of the
      International Commission on Occupational Health (ICOH, 1992); 2) The Code of
      Conduct of the National Association of Company Doctors (ANMA, 1997); 3) The
      Technical and Ethical Guidelines for workers' health (ILO, 1998). The chief
      purpose of all these documents is to safeguard the health of workers and to
      guarantee the safety of the workplace by defining programmes of health
      supervision to match specific risks. The methods should be non-invasive and
      should allow for a check or efficiency. The physician is expected to have a high
      degree of professionalism and up-to-date skills; to be independent and impartial;
      to be reserved and capable of inter-disciplinary co-operation. On the basis of
      the above documents, a number of problematic aspects may be appraised concerning
      the relationship between the occupational health physician responsible for the
      surveillance activities of the local health authority and the relative company
      physician. The documents stress the importance of keeping up to date and of
      quality, fields in which the dominant role played by Scientific Societies is
      underlined. Finally it is recommended that health supervision be arranged in such
      a manner as to foster the professionalism and responsibility of the physician in
      charge rather than the formal implementation of health-care procedures that are
      inadequate and not in line with up-to-date scientific knowledge.

PMID- 10911558
TI  - [Health surveillance: from risk presumption to risk assessment].
AB  - A working group of the Occupational Medicine and Industrial Hygiene Association
      of Lombardy, the National Association of Occupational Health Physicians the
      National Society of Prevention Operators made a paper in order to rationalize the
      sanitary surveillance, observing the laws in force and following the European
      Directives. The authors, thinking that everyday experience not very useful health
      examinations are carried out and that the sanitary surveillance should be planned
      according to the real working risks, give methodological directives about the way
      to make the mandatory clinical examinations less frequent, to the firms, to the
      occupational health physician and to the public occupational health operators of
      the local health units that must supervise the sanitary surveillance.

PMID- 10911559
TI  - [Point of view of the magistrate].
AB  - The authors agrees to the three associations proposal that is useful and
      juridically correct. He considers all the situations that make the sanitary
      surveillance mandatory and assert the need of a common interpretation of the law
      that must fallow the new pattern pointed out by the legislative decree 626/94,
      respecting the European Community directives. Consequently the rules provided by
      the decree 303/56 should be interpreted in the light of the legislative decree
      626/94 principles.

PMID- 10911560
TI  - [Application of article 35 of the DPR 303/56: experience of the operators of the
      Public Occupational Services and competent physicians. Sample survey].
AB  - In the last three years 450 requests of derogation to the article 35 of
      legislative decree 303/56 reached one third of the Public Occupational Services,
      with a clear progressive increase of their number. The working risks derogation
      is most frequently requested for are: solvents, welding fumes and metallic dusts.
      The operators of the Public occupational Services employed these criteria to
      grant the derogation: the effectiveness of the prevention, the low concentrations
      of the harmful agents, the occasionality of the unhealthy working, the risk lack
      or scarcity. In the 80% of the cases the operators of the Public Occupational
      Services made an inspection in only two cases they notified breaches of the law.
      350 (70%) of the requested derogation were granted, 10 (20%) are now under
      evaluation, 90% (20%) were not allowed. In conclusion we point out that the use
      of the article 35 in industries with an adequate safety organization, by means of
      the dilution of the periodical clinical examinations, allows to better fit the
      health surveillance programs to the real working risks.

PMID- 10911561
TI  - [Application of article 35 of the DPR 303/56: experience of the competent
      physicians].
AB  - The "competent" doctor is much interested in the extensive application of the
      article 35 of DPR 303/56. As a matter of fact, that permits him a sanitary
      surveillance less concerned in formal performances and more related to work risk.
      The employers are often reluctant to require the derogation foreseen by the
      article 35 of DPR 303/56 because from such a request interventions on part the
      vigilance organ could derive causing instruction report report, notices and
      sanctions regarding situation independent from the risk which the derogation was
      requested. As a result, the modality for the derogation application has to be
      uniform all over the territory: an action at regional level is strictly necessary
      as well as check activity on part of the competent offices of the region.

PMID- 10911562
TI  - [Point of view of the entrepreneurs].
AB  - The main purpose of a business is the improvement, or rather as nowadays is said,
      when one speaks of total quality, the continue improvement. According with that
      entrepreneurs absolutely agree with the "oldness" of the decree 303/56 and with
      the involvement of scientific associations, the trade unions, or rather, or
      people that engage in prevention and workers safety. However it is necessary to
      keep in mind, in a high competitiveness setting and beyond the differences among
      the firms the difficulties for the business, in particular if it is of middling
      small size, in making an accurate risk assessment.

PMID- 10911563
TI  - [Point of view of the trade union].
AB  - The goal is "make healthy individuals in healthy organizations". The workers
      health tutorship isn't in contrast with the business purpose, if the business
      considers the workers health a development factor. He doesn't agree with so
      frequent clinical examination, that are useless. However we can't leave the
      sanitary surveillance, that must involve a lager number of workers indeed. The
      occupational health physician must be involved in the risk assessment and pay
      attention to the information coming from the workers. The public service must
      make the occupational health physician activity more effective, giving them a
      line.

PMID- 10911564
TI  - [Health surveillance in the parliamentary proposal for the development of a
      single text of general regulations for the protection of health and work safety].
AB  - The goal of the Work Commission of the Senate, making a proposal of a
      consolidation of several regulations in force, inspired to different
      philosophies, sometimes going to long time ago. The commission intends to issue
      an "up to date" law. With regard to the sanitary surveillance, physicians
      independence and capacity are of paramount importance. The physician capability
      on a continuous updating. The occupational health physician is concerned with the
      relationship between people and environment, therefore is duty can not come to
      the mere clinical examination: he must be involved in risk assessment, a basic
      factor in prevention, that must be absolutely reliable.

PMID- 10911565
TI  - [Proposals on health surveillance contained in the bill No. 2389 presented by
      Senator Smuraglia].
AB  - The Italian Interassociative Council for the Prevention has examined the bill n.
      2389 of senator Smuraglia, expressing appreciation for the initiative (demanded
      since a long time by the operators of the field) and for the remarkable
      commitment in the drawing up of such an extensive and well-organized text. At the
      same time the IICP set up and forwarded to senator Smuraglia some notes and
      additional proposals, as well as proposals for partial changes, on the following
      topics:--employer's functions--relationship between the employer and the
      surveillance bodyprevention and protection service--medical surveillance and
      "Competent Doctor" threshold limit values--informational system--institutional
      expertise--omologation--penalty system. In this report we quote the notes
      expressed with reference to the chapter about the medical surveillance and the
      competent doctor, of interest of this meeting. We can anticipate with
      satisfaction that senator Smuraglia admitted many of our proposals and that on
      their basis he signed a few amendments. Between the proposals we suggested I
      would like to mention the one concerning the overcoming of the existing medical
      surveillance system. This is a strict system, essentially outlined by the Law
      303/56 (article n. 33) and by the Law 1124/65, by now inadequate with reference
      to the new working reality and to the current pathology correlated to it. We
      submit some considerations and the first hypothesis on the constructions of a
      model of medical surveillance more flexible and open, in conformity with the new
      reality and the recommendations of the E.U.

PMID- 10911566
TI  - [Parliamentary proposal for health surveillance in the single text bill].

PMID- 10911567
TI  - [Round Table "Role of scientific and professional associations in proposing
      occupational health programs to regional and national authorities].
AB  - The six participants at the round table were experts in the field of Occupational
      Prevention working respectively in the Ministry of Health, the National Institute
      of Occupational Health, the Health Council of Lombardy, the Law-court of Milan,
      the CGIL Trade Union, and the Lombard Employers Association. All the participants
      were of one mind on the establishment of working groups within the scientific and
      professional associations with the aim of preparing and updating occupational
      exposure limits, diagnostic records, programs of biological and environmental
      monitoring, etc. Moreover, they stressed the need to establish permanent
      cooperation between the scientific and professional associations and the regional
      and national health authorities. These associations can make an important
      contribution, for example in preparing new preventive guidelines, because they
      can act faster than the legislative bodies. The validity of these proposals was
      confirmed by the judge attending the round table. He stated that technical
      standards proposed by groups of professionals or by scientific associations have
      usually been taken into consideration when relevant legislation has been applied.

PMID- 10911568
TI  - [Circular No. 31/SAN/99. Increase in the current frequency of health assessment
      imposed by the DPR 303/56 and criteria for the granting of derogation].

PMID- 10911569
TI  - [Waste of neural networks?].

PMID- 10911570
TI  - [Work suitability: toxic gas management and certificate of competence for
      operations related to their use].

PMID- 10911571
TI  - Prolonged culture of human cryopreserved embryos with recombinant human leukemia
      inhibitory factor.
AB  - PURPOSE: To evaluate the efficiency of recombinant human leukemia inhibitory
      factor (LIF) in the prolonged culture of human cryopreserved-thawing embryos.
      METHODS: After thawing, all embryos were divided into four groups: (1) Human
      tubal fluid (HTF), (2) HTF + LIF, (3) M3TH medium, and (4) M3TH medium plus LIF.
      Following prolonged culture, embryo development in each group was compared.
      RESULTS: In embryo development from about the 2- to 4-cell to 9- to 16-cell
      stage, there were nonsignificant differences between each group. There was lower
      morula formation rate in group 1 (6.9%) than those in other groups (23.2%, 19.7%,
      23.1%). The lower blastocyst formation in group 1 and 3 (0%, 0%) than those in
      group 2 and 4 (11.0%, 12.8%) were noted. CONCLUSIONS: LIF is beneficial for
      preimplantation embryos. LIF does not influence the early embryo development. LIF
      supplemented HTF provided a similar culture environment for thawing embryos as
      LIF-supplemented M3TH medium.

PMID- 10911572
TI  - Comparison of zona manipulated and zona intact blastocyst transfers: a
      prospective randomized trial.
AB  - PURPOSE: In this prospective randomized study the effects of enzymatic treatment
      of zona pellucida of blastocysts on implantation and pregnancy rates were
      evaluated in a group of patients who had more than five embryos on day 3.
      METHODS: Forty-six patients with a mean age of 29.8 +/- 4.5 years and mean
      duration of infertility of 6.72 +/- 0.63 years had blastocyst stage transfers,
      with a mean number of 2.9 +/- 0.1 embryos replaced per patient. Patients were
      randomly divided into two groups. The first group consisted of patients (n = 22)
      who had zona intact blastocyst stage transfers and the second group consisted of
      patients (n = 24) who had zona manipulated (enzymatic treatment) blastocyst stage
      transfers. Patient and cycle characteristics were similar in both groups. A
      commercial cell and serum-free sequential culture system was used for all
      embryos. RESULTS: Overall blastocyst formation rate was 50.3%. Transfer could be
      done in all patients. The positive beta-human chorionic gonadotropin rate in the
      zona intact group was 50% (11/22) and in the zona-manipulated group was 70.8%
      (17/24). Clinical pregnancy, ongoing pregnancy, and implantation rates in zona
      intact and manipulated groups were 45.5%, 27.3%, and 19%, and 62.5%, 45.8%, and
      24% respectively. Although implantation and pregnancy rates in the zona
      manipulated group were higher, there were no statistically significant
      differences in terms of these variables between two groups. No triplet pregnancy
      was obtained in either group, and the twin pregnancy rate was 20% (2/10) in the
      zona intact group and 13.3% (2/15) in the zona-manipulated group. CONCLUSIONS:
      With further improvements in the embryo culture systems it will become possible
      in the near future to achieve high implantation rates even with single blastocyst
      transfers. Enzymatic treatment of the zona pellucida seems that it does not alter
      the pregnancy and implantation rates, but further studies with larger group of
      patients are needed to clarify the real effect of this zona manipulation on
      pregnancy outcome.

PMID- 10911573
TI  - Does pretreatment with progestogen or oral contraceptive pills in low responders
      followed by the GnRHa flare protocol improve the outcome of IVF-ET?
AB  - PURPOSE: Women undergoing in vitro fertilization with low ovarian reserve and
      poor response to controlled ovarian hyperstimulation (COH) present a management
      dilemma. In a retrospective observational study, we compared the pretreatment use
      of the gestogen medroxyprogesterone acetate (10 mg twice daily from day 15 of the
      cycle for a minimum of 2 weeks) with an oral contraceptive pill (one tablet daily
      from day 4 of the cycle for a minimum of 3 weeks). METHODS: The criteria for
      inclusion in the study included one or more of the following: abandoned cycles
      due to poor response, fewer than four oocytes retrieved following a standard COH
      protocol, age > 39 years, and elevated basal serum follicle-stimulating hormone
      (FSH). Thirty-eight women received pretreatment with gestogen, and a similar
      number of women received pretreatment with the pill. The flare protocol was used
      in all treatment cycles combined with an individualized dose of human menopausal
      gonadotropin (hMG) (4-8 ampoules/day of 75 units FSH/ampoule) depending on
      previous response, age, and early follicular serum FSH level. Both groups were
      similar in mean age, duration of infertility, early follicular FSH levels, and
      the distribution of various aetiologies. RESULTS: Twenty-nine cycles were
      abandoned before oocyte retrieval, 15 (39.5%) in the pill group and 14 (36.8%) in
      the gestogen group, because of an inadequate ovarian response. The mean (+/- SD)
      number of ampoules (75 IU FSH/ampoule) of hMG used per cycle was similar in the
      pill and gestogen groups (59.7 +/- 19.3 vs. 70.2 +/- 29.4, respectively). There
      also was no difference seen in the numbers of oocytes retrieved (4.4 +/- 2.3 vs.
      4.2 +/- 2.5), total number of embryos (2.5 +/- 2.4 vs. 2.2 +/- 1.1), or the
      number of embryos transferred (1.8 +/- 1.2 vs. 2.1 +/- 1.0) in the pill and
      gestogen groups, respectively. One pregnancy in each group resulted following
      embryo transfer in 22 women in the pill group and in 24 women in the gestogen
      group. CONCLUSIONS: We conclude that pre-IVF treatment with oral contraceptive
      pill or gestogen combined with the flare protocol in women at high risk of or
      with a history of poor ovarian response, as defined in this study, did not appear
      to result in an improvement in outcome of IVF-embryo transfer.

PMID- 10911574
TI  - The effect of human fallopian tube epithelium on human sperm velocity motility
      and binding.
AB  - PURPOSE: A prospective, controlled in vitro study was conducted to evaluate the
      effects of human fallopian tube epithelium on the motility, velocity, and binding
      of human spermatozoa. METHODS: Eleven fallopian tubes from six women undergoing
      hysterectomy and semen samples from 14 male partners of women undergoing in vitro
      fertilization were collected. Human spermatozoa were cultured with monolayer of
      human fallopian tube epithelial cells. The motility and velocity were analyzed
      subsequently at 0, 2, 6, 24, and 48 hr of incubation. The sperm binding capacity
      was analyzed after 48 hr in the hemizona assay (HZA). RESULTS: The presence of
      the human fallopian tube epithelial cells did not have any beneficial effects on
      sperm motility and velocity. On the other hand, significant promoting effect was
      observed in the ability of the sperm to bind to the zona pellucida. CONCLUSIONS:
      The interaction of human spermatozoa with fallopian tube epithelial cells
      significantly increases sperm binding in the HZA.

PMID- 10911575
TI  - Analysis of spermatozoa from seven ICSI males with constitutional sex chromosomal
      abnormalities by fluorescent in situ hybridization.
AB  - PURPOSE: The objective was to estimate the risk for subfertile males with a
      constitutional sex chromosomal abnormality of transmitting such a chromosome
      abnormality to their children, conceived by intracytoplasmic sperm injection
      (ICSI). METHODS: Semen samples were obtained from seven severely oligospermic
      ICSI candidates. Six of them had a numerical sex chromosomal abnormality,
      including mosaic 45,X/46,XY, mosaic 46,XY/47, XXY, 47,XXY (Klinefelter's
      syndrome), and 47,XYY. One male had a structural abnormality, namely, an
      inversion of the Y chromosome. The semen was studied by three-color fluorescent
      in situ hybridization (FISH) with probes specific for chromosomes 18,X, and Y.
      RESULTS: Chromosomal aneuploidy rates of any of the three chromosomes were
      significantly higher than the aneuploidy rates observed in three control samples
      but comparable to the rates observed in 10 ICSI candidates with
      oligoasthenoteratozoospermia (OAT) and a normal constitutional karyotype.
      CONCLUSIONS: Our data indicate that males with (mosaic) sex chromosomal
      abnormalities have no higher risk of producing offspring with a sex chromosomal
      abnormality by ICSI than OAT males with a normal karyotype.

PMID- 10911576
TI  - Physiological induction of the acrosome reaction in human sperm: validation of a
      microassay using minimal volumes of solubilized, homologous zona pellucida.
AB  - PURPOSE: The objective was to develop a method that could accommodate
      microvolumes of solubilized human (ZP) and sperm for assessing the induction of
      the acrosome reaction. METHODS: A microassay using 1 microliter of 2.5, 1.25,
      0.6, 0.3, and 0.125 ZP/microliter incubated with 1 microliter of a highly motile
      sperm suspension for 60 min. As a control and parallel to the microassay a
      standard acrosome reaction technique was performed. RESULTS: No significant
      differences were observed between the percentage acrosome-reacted sperm reported
      by the two assays under basal conditions (spontaneous) or after induction with a
      Ca2+ ionophore or solubilized ZP. At a ZP concentration of 0.6 ZP/microliter, the
      percentages of acrosome-reacted spermatozoa in both techniques were significantly
      higher compared to the spontaneous acrosome reaction results, namely 18% and 17%,
      compared to 10% and 10%, respectively. Approximately a 30% level of acrosomal
      exocytosis was induced with 2.5 ZP/microliter both methods. CONCLUSIONS: This
      newly devised microtechnique is easy and rapid to perform, is repeatable, and
      facilitates the use of minimal volumes of solubilized human ZP (even a single ZP)
      for assessment of the inducibility of the acrosome reaction of a homologous sperm
      population.

PMID- 10911577
TI  - Hyaluronic acid inhibits apoptosis in granulosa cells via CD44.
AB  - PURPOSE: This study was designed to examine whether hyaluronic acid (HA) inhibits
      apoptosis in cumulus and mural granulosa cells and to examine whether this effect
      of HA was mediated through CD44. METHODS: Mural and cumulus granulosa cells were
      obtained from in vitro fertilization patients. The cells were cultured with
      various concentrations of HA or HA plus various concentrations of anti-CD44
      antibody without serum supplement. After 24 hr of culture, the cells were fixed
      and stained with Hoechst 33258. One thousand granulosa cells of each conditions
      were observed by fluorescence microscopy. RESULTS: HA inhibited apoptosis in both
      kinds of granulosa cells, and anti-CD44 antibody prevented this effect of HA.
      CONCLUSIONS: The incidence of apoptotic granulosa cells with fragmented condensed
      nuclei was reduced by HA via CD44.

PMID- 10911579
TI  - Low-dose aspirin for infertile women with thin endometrium receiving intrauterine
      insemination: a prospective, randomized study.
AB  - PURPOSE: The objective was to evaluate the effect of aspirin on infertile women
      with thin endometrium. METHODS: Patients who had thin endometrium (< or = 8 mm)
      and intrauterine insemination were divided into the aspirin and nonaspirin
      groups. Endometrial pattern (trilaminar and nontrilaminar) and thickness, the
      pulsatility index (PI) and resistance index (RI) of the uterine artery, spiral
      artery, and ovarian dominant follicles, and pregnancy rates of both groups were
      measured. RESULTS: A total of 114 and 122 women were included in the aspirin and
      nonaspirin groups, respectively. There were significantly higher percentages of
      trilaminar endometrium (46.5% vs. 26.2%) and pregnancy rate (18.4% vs. 9.0%)
      after aspirin therapy. There was nonsignificant difference in the endometrial
      thickness, and PI/RI values of the uterine artery, spiral artery, and ovarian
      dominant follicle between both groups. CONCLUSIONS: Higher pregnancy rate and
      better endometrial pattern were achieved in patients with thin endometrium after
      aspirin administration. Aspirin therapy could not significantly increase the
      endometrial thickness and the resistance of uterine and ovarian flow.

PMID- 10911578
TI  - Effects of aging on ovarian fecundity in terms of the incidence of apoptotic
      granulosa cells.
AB  - PURPOSE: The objective was to determine the effects of women's age on the ovarian
      fecundity as assessed by the incidence of apoptotic granulosa cells. METHODS:
      Twenty-eight normo-ovulatory women underwent ovulation induction for standard
      IVF. The husbands of these women showed severe male infertility factors. The
      women were divided into four groups according to their ages. Women underwent
      follicle aspiration after the administration of human menopausal gonadotropin
      plus human chorionic gonadotropin. The nuclei of granulosa cells were examined by
      using fluorescence microscopy, and the incidence of apoptotic granulosa cells was
      tabulated. RESULTS: Granulosa cells in the older women revealed a significant
      increase in the number of apoptotic cells. The number of total oocytes and the
      number of mature oocytes obtained significantly decreased with age. However,
      endometrial thickness and follicular estradiol, progesterone, and free
      testosterone levels were not significantly different among four different age
      groups. CONCLUSIONS: Age increases apoptotic changes in granulosa cells and
      consequently decreases the ovarian fecundity.

PMID- 10911580
TI  - Use of a laser to evaluate zona pellucida hardness at different stages of mouse
      embryonic development in vitro and in vivo.

PMID- 10911581
TI  - Survival and subsequent in vitro development of hamster embryos after exposure to
      cryoprotectant solutions.

PMID- 10911583
TI  - So why haven't I seen that manuscript?

PMID- 10911582
TI  - Induction of early pregnancy factor from mouse metoestrous ovaries and oviducts
      in vitro by steroid hormones.

PMID- 10911585
TI  - Keeping active can prevent Alzheimer's disease.

PMID- 10911584
TI  - Psychiatric problems in children linked to exposure to violence.

PMID- 10911586
TI  - Exploring the factors influencing relapse and recovery among drug and alcohol
      addicted women.
AB  - 1. Both women who were in treatment for relapse to and in sustained recovery from
      drugs and alcohol had multiple co-occurring addictions such as relationship,
      spending, food, and shopping that complicated the recovery process. 2. Depression
      is a major trigger for relapse in women with alcohol and drug problems.
      Recognition and treatment of depression is critical to achieve successful
      outcomes of treatment for these women, and teaching them to monitor their mood
      changes and seek help will improve the chances of preventing relapse. 3. Subjects
      in neither the relapse nor recovery sample recognized the significant influence
      of current violent partnerships or the ending of a violent relationship on their
      relapse or recovery.

PMID- 10911587
TI  - Suicide awareness at the elementary school level.
AB  - 1. Suicidal behavior is a real and growing problem in elementary school-age
      children. 2. Childhood suicides often are mistaken for accidents. 3. Knowledge is
      an effective tool in preventing suicides. It is imperative that suicide awareness
      and orientation for all school staff and parents be initiated at the elementary
      school level.

PMID- 10911588
TI  - Young widows' experience with an Internet self-help group.
AB  - 1. Finding empathetic support is an important factor in coping for people with
      various needs. 2. Support group resources may be limited due to long travel
      distances, expense of child care, lack of transportation, or no available group
      for specific needs. 3. Nurses can guide their patients to Internet support groups
      for self-care when traditional groups are not accessible or applicable to their
      circumstances.

PMID- 10911589
TI  - Effectiveness of use of home health nurses to decrease burden & depression of
      elderly caregivers.
AB  - The purpose of this research was to investigate the impact of home health nursing
      intervention on burden and depression of elderly caregivers who were caring for
      an ill relative in their home. Two groups of caregivers were compared for
      differences in caregiver burden and depression. The caregivers in the control
      group did not use the services of home health nurses, whereas the caregivers in
      the experimental group did use these services. Data were analyzed using the
      Burden Interview and the Center for Epidemiologic Studies Depression Scale.
      Multiple analysis of variance confirmed that caregivers who used the services of
      home health nurses were significantly less burdened and less depressed than
      caregivers who did not use these services.

PMID- 10911590
TI  - The global challenges of the HIV/AIDS pandemic.

PMID- 10911591
TI  - The sociological spread of HIV/AIDS in South Africa.
AB  - South Africa (SA) now accounts for more than 50% of newly reported HIV cases in
      sub-Saharan Africa annually. In 1993, approximately 90% of those reported as HIV
      positive in SA were of African descent. This paper examines sociological factors
      in the spread of HIV in SA through the application of Lalonde's (1974) Health
      Field Concept. SA's emerging District Health System (DHS) is discussed, as well
      as barriers to effective implementation and recommendations. Through Lalonde's
      sociopolitical view of health, a coordinated and multisectorial approach to
      HIV/AIDS in SA can be established. Without this approach, health care
      interventions will fail to target the population effectively, thereby reducing
      effectiveness and sustainability.

PMID- 10911592
TI  - Effects of an empowerment program on coping, quality of life, and the maternal
      role adaptation of Thai HIV-infected mothers.
AB  - The objective of this study was to explore strategies for improving the
      appropriateness of a health care delivery model to meet HIV-infected mothers'
      complex needs. A participatory action research paradigm was used as a process for
      an empowerment program (EP) and to elucidate the essential components of the
      program identified by these mothers. To test the EP's effectiveness, a
      nonequivalent control group pretest-posttest, quasi-experimental design was used.
      The participants included 94 Thai HIV-infected mothers rearing their own infants,
      with 46 in the 6-week experimental group and 48 in the control group. Study
      findings showed that the mothers in the EP group significantly increased levels
      of coping ability, quality of life, and maternal role adaptation when compared to
      mothers in the control group. In addition, data analysis revealed five components
      of the EP that were identified by mothers as essential for HIV-infected mothers'
      psychological well-being and their maternal role adaptation. These interventions
      included peer group meetings, professional support on infant rearing and maternal
      self-care, stress management, access to available social support, and alternative
      medicine. The mothers reported greater autonomy, accountability, collegiality,
      and more effective communication by the implication process of the EP.

PMID- 10911594
TI  - Current status of the HIV/AIDS pandemic in Tanzania.

PMID- 10911593
TI  - Patterns of partnership and condom use in two communities of female sex workers
      in Tanzania.
AB  - Two rapid ethnographic studies have found that commercial sex workers (CSWs) and
      other high-risk women in Tanzania have different categories of partners, ranging
      from single-time contacts to long and enduring relationships. Since the advent of
      HIV/AIDS prevention programs in Tanzania in the late 1980s, CSWs and their
      clients have been aware of the multiple benefits of condom use for the prevention
      of pregnancy and STDs including HIV. These women often use condoms for the single
      time contact. However, since the HIV/AIDS epidemic, casual partners have
      decreased in number. These days, most of their sexual contacts occur within long
      term partnerships, and within these relationships, condom use is rare. Although
      the message that condoms should be used during high-risk behavior has been
      largely accepted, the definition of a high-risk relationship needs to be extended
      from casual partnerships to include multiple long-term partnerships. In addition,
      men and women's empowerment through education, business, and equal rights needs
      to be addressed at all levels of society.

PMID- 10911595
TI  - The collaborative project: an effective Canadian partnership in HIV/AIDS nursing
      care.
AB  - Since 1995, the Canadian Association of Nurses in AIDS Care (CANAC), the Canadian
      Nurses Association, the Victorian Order of Nurses of Canada, and the Ordre des
      Infirmieres et Infirmiers du Quebec have collaborated on several HIV/AIDS
      initiatives supported by the AIDS Care, Treatment, and Support Program, Health
      Canada (the national health organization). CANAC is the lead and sponsoring
      association in this collaboration. Phases I and II of the collaboration (December
      1996 to March 1999) identified, promoted, and evaluated 17 nursing projects in
      HIV/AIDS care across Canada. This article describes the goals and outcomes of two
      of the collaboration's main projects: the identification of HIV/AIDS nursing
      research priorities and the mentorship program in HIV/AIDS care for Francophone
      nurses practicing in the province of Quebec.

PMID- 10911596
TI  - How home care agencies in Germany view the AIDS challenge: results of an
      exploratory study.
AB  - The purpose of this article is to examine the current state of home care services
      for people living with HIV/AIDS and other seriously ill patients in Germany. It
      is based on a research project promoted by the Federal Ministry for Labor that
      aimed to investigate the possibilities and problems related to home care of the
      critically ill and thus establish basic scientific principles that could be used
      to close a health care gap that has long been of concern. The article will
      initially offer a brief explanation of the causes underlying the current problems
      in the field of home care for seriously ill patients. The authors then present
      the implications for nursing qualification that will have to be addressed to
      develop a patient-oriented, priority-level home nursing care program for people
      with HIV/AIDS in Germany.

PMID- 10911597
TI  - Telephone support for Canadian nurses in HIV/AIDS care.
AB  - An assessment study was conducted with Canadian nurses (N = 177) in HIV/AIDS care
      to determine how social support influences the relationship between job stress
      and health (job satisfaction and burnout). The assessment study revealed that
      social support and coping both moderate the effects of these stressors on nurses'
      health and functioning outcomes (i.e., job satisfaction and burnout).
      Accordingly, the follow-up study tested the effectiveness of an intervention
      designed to enhance social support, promote the use of certain coping strategies
      for managing occupational stress, and prevent burnout in nurses. Telephone
      support groups, co-led by an expert facilitator and an expert AIDS nurse, were
      tested in a demonstration project for nurses in HIV/AIDS care (n = 30). The nurse
      participants reported that the intervention enhanced their coping, confidence,
      relationships, client care, and connections to the HIV/AIDS nursing community.

PMID- 10911598
TI  - The role and function of the HIV/AIDS coordinator nurse in Japan.
AB  - HIV/AIDS coordinator nurses (CNs) are key professionals in ensuring the provision
      of quality health care to patients with HIV/AIDS and to their families. Through
      this case study, the functions of the HIV/AIDS CN in Japan were identified, and
      an initial model of the HIV/AIDS CN role was developed. Four categories of
      responsibility were identified: (a) assessment, (b) diagnosis of nursing
      problems, (c) coordination, and (d) other related nursing activities. The
      category of other nursing activities included four subcategories. These were (a)
      consultation, (b) patient education, (c) expansion of the patient's support
      network, and (d) administrative or office work. These categories and
      subcategories contribute to an understanding of the role of the HIV/AIDS CN.

PMID- 10911599
TI  - Teaching HIV-infected outpatients the self-administration of subcutaneous
      interleukin-2 and strategies for symptom management.

PMID- 10911600
TI  - [Thrombosis of the basilar artery--a rare differential sudden deafness diagnosis
      and vestibular failure].
AB  - BACKGROUND: Occlusion of basilar artery is a rare and life-threatening event. A
      quick and safe diagnosis and initiation of adequate therapy are decisive. For the
      ENT-specialist it is important to know that this thrombosis, which runs a lethal
      course in many cases, can develop with a disturbance of hearing and/or vestibular
      function as initial symptoms. PATIENTS: Reported are four cases of thrombosis of
      the basilar or vertebral artery. Two out of four patients contacted the ENT
      emergency unit because of symptoms of acute vestibular neuritis, one patient was
      previously diagnosed with sudden deafness by a local ENT-specialist, one patient
      was treated for hypertension induced epistaxis in one of our wards. Only one
      patient initially presented additional neurological symptoms, causing suspicion
      for a brainstem lesion as well. However these symptoms were only noticed on close
      examination. By immediate anticoagulation therapy (with Heparin) progress of
      thrombosis could be avoided. The patient showed a complete recovery and was free
      of any symptoms two years after thrombosis. Two of the other two patients
      developed a delayed onset of neurological symptoms next to the initial symptoms
      of vestibular and cochlear affection (within 24 hours), therefore diagnosis of
      thrombosis was late and despite of immediate anticoagulation therapy (with
      Heparin) both patients died. The one patient treated for hypertension induced
      epistaxis developed only discrete symptoms of basilar artery thrombosis,
      nevertheless he was diagnosed and treated immediately. He made a complete
      recovery and was dismissed two weeks later. CONCLUSIONS: It is therefore
      necessary to carefully control and sometimes correct diagnosis in cases of sudden
      deafness and acute vestibular neuritis. Especially additional neurological
      symptoms indicate the necessity of a MRI-angiogram or CT-(angiography)scan to
      exclude thrombosis of the basilar artery.

PMID- 10911601
TI  - [Inner ear depression after middle ear interventions].
AB  - BACKGROUND: Any type of otosurgical procedure involves the risk of inner ear
      damage. As middle ear surgery is also performed for functional reasons this risk
      should be taken into consideration. The aim of this study was to analyse the
      frequency and the nature of sensorineural hearing loss following chronic ear
      surgery. PATIENTS: A total of 3989 middle ear cases operated on between 1991 and
      February 1999 at the Department of Otorhinolaryngology, Head and Neck Surgery,
      University of Wurzburg, Germany were studied retrospectively: 781 type I
      tympanoplasties, 2408 type III tympanoplasties and 800 cases of stapes surgery.
      The pre- and the postoperative audiograms in the frequency range between 500 and
      8000 Hz were analysed and correlated to the different intraoperative findings.
      RESULTS: Sensorineural hearing loss occurred in a total of 1.3% of 2224 patients
      with normal preoperative bone conduction thresholds: 0.2% became deaf, 0.8%
      acquired a high tone loss at 4 kHz and in 0.3% patients also 2 kHz was affected.
      None of the documented intraoperative complications such as bleeding, unexpected
      opening of a semicircular canal, extensive manipulation at the ossicular chain or
      a gusher phenoma showed a relevant effect on postoperative bone conduction
      thresholds. The incidence of high tone loss was not increased in cases of
      extensive drilling of the temporal bone. An unexpected opening of the vestibulum
      led to a small, but statistically significant change in postoperative bone
      conduction thresholds. CONCLUSIONS: Our results demonstrated that the risk for
      sensorineural hearing loss caused by middle ear surgery is low. None of the
      analysed factors seems to be a relevant prognostic risk factor for postoperative
      inner ear depression.

PMID- 10911603
TI  - [Meta-analysis of laser-assisted uvulopalatopharyngoplasty. What is clinically
      relevant up to now?].
AB  - BACKGROUND: Laser-assisted uvulopalatoplasty (LAUP) was not recommended by the
      American Sleep Disorders Association for the treatment of snoring and obstructive
      sleep apnea (OSA) because of data lacking in 1994. In the meantime numerous new
      papers concerning this subject have been published in peer reviewed journals. A
      new evaluation of the value of LAUP is presented. METHODS: In a world-wide
      literature search (Medline) from 1980 until March 1999, seventy articles were
      identified. The papers were analyzed concerning the subtopics "operative
      techniques", "LAUP and OSA", "LAUP and snoring", "pain", "side-effects",
      "indications" and "predictive criteria". RESULTS: On the basis of the collected
      data, it is possible to put definitive values on the subtopics "operative
      techniques", "LAUP and snoring" and "side-effects". In contrast, objective long
      term results concerning "LAUP and OSA" are still missing. Short-term results are
      promising. CONCLUSION: Nevertheless, LAUP and its related procedures presently
      should not be recommended for the treatment of any severity of OSA.

PMID- 10911602
TI  - [A new system for the classification of ethmoid polyposis. Effect of combined
      local and systemic steroid therapy].
AB  - BACKGROUND: Nasal polyps are a common disease with in the majority of cases
      unknown origin. Both the medical and surgical treatment of nasal polyps present a
      challenge in Otorhinolaryngology. METHODS: We developed a four-stage grading
      system for nasal polyps based on the endoscopic aspect of more than 300 patients.
      In a study of 37 patients, treated by systemically (Methylprednisolon 64 mg p.o.,
      decreasing amounts for the first 11 days) and locally (Budesonid 400 micrograms
      intranasal) applied steroids for 90 days, this staging-system was tested.
      RESULTS: The mean stage of polyps decreased significantly (p < 0.01) from 2.8 at
      day 0 to 1.7 at day 7 and further to 1.2 and to 0.7 at day 28 and day 90
      respectively. The mean nasal symptom score decreased equally from 1.14 on day 1
      to 0.19 and to 0.14 on day 7 and day 28 respectively. To summarize, we observed a
      significant (p < 0.01) decrease in polyp stages of 75% respectively a significant
      (p < 0.01) reduction of symptom scores of 93%. CONCLUSIONS: Thus, we present a
      suitable new grading system for nasal polyps which we applied directly to assess
      the efficacy of combined local and systemic steroid therapy. It was shown that
      this treatment can reduce polyps and prevent their recurrence over the observed
      time.

PMID- 10911604
TI  - [Speech improvement with velopharyngoplasty in patients with lip-jaw-palate
      clefts].
AB  - BACKGROUND: Despite successful closure of the hard and soft palate and intensive
      speech therapy a velopharyngeal insufficiency is not completely avoidable in each
      case of cleft palate. An improvement by velopharyngoplasty should be possible.
      PATIENTS AND METHODS: Two hundred and ninety patients suffering from cleft palate
      were examined before and one year after velopharyngoplasty according to Sanvenero
      Rosselli. Four main symptoms of the affected speech were assessed: changes of the
      resonance, inappropriate nasal air emission, articulary disorders (deviations
      from articulation areas), and non-physiological facial expression during
      speaking, each divided into three grades. Afterwards, the complete speech quality
      was classified. RESULTS: Assessing the symptoms separately and summarised the
      therapy including velopharyngoplasty was suitable to improve the speech quality
      in 83.1% of the cases, resulting in a widely unaffected speech. The improvement
      was greater in younger patients undergoing operation (Gamma-test, p < 0.001). But
      the final results were independent from age due to poorer initial situation in
      younger patients (Gamma-test, p < 0.001). CONCLUSIONS: The velopharyngoplasty is
      an important method for repair of velopharyngeal insufficiency in patients with
      cleft palate. In each individual case it is necessary to consider carefully if
      and when this operation should be performed. An intensive interdisciplinary co
      operation of all specialists involved in the treatment is indispensable.

PMID- 10911605
TI  - [Intraoperative neurophysiological monitoring (IONM) of the recurrent laryngeal
      nerve and microdissection. Surgical techniques for decreasing the risk of
      recurrent laryngeal nerve paralysis].
AB  - BACKGROUND: Frequently numerous recurrent laryngeal nerve injuries occur after
      operations on the thyroid glands. Compared with postoperative permanent
      hypocalcemia, unilateral and especially double-side recurrent paresis pose
      serious complication. As early as 1938 specialists [1] pleaded for a routine
      visualisation of the nervus recurrens in operations of the thyroid gland, to
      reduce the risk of permanently recurring paresis. In controversial discussions of
      the matter specialists have opted for a demonstration of the nerve also under
      medico-legal aspects. Implementing functionally-critical operational strategies
      requires the choice of an anatomically suitable operative procedure for the
      removal of morphological, functional and oncological changes, as well as the
      avoidance of complications. METHOD: Intra-operative Monitoring is highly
      recommendable as a neurophysiological method of supervision combined with
      microdissection to ensure the safe handling of recurrent laryngeal nerve.
      CONCLUSION: The rate of permanent paresis on the recurrent nerve can be lowered
      to less than 1 per cent when this is used as a routine procedure for all
      operations and the treatment of the thyroid gland diseases.

PMID- 10911607
TI  - [The value of hyperbaric oxygen therapy (HBO) in treatment of problem wounds in
      the area of plastic-reconstructive head and neck surgery].
AB  - BACKGROUND: Hyperbaric oxygenation therapy is presently predominantly discussed
      in connection with sudden deafness and tinnitus. Amongst this ongoing
      controversy, the primary indications of this in the middle of the 20th century
      established therapy, especially in regard to problem wounds in the plastic
      reconstructive surgery go mainly underrated. The present paper reviews the
      attention towards this area in plastic surgery. PATIENTS AND METHODS: Three
      typical cases (traumatic nasal tip reconstruction, wound ulceration after
      radiotherapy and lobe necrosis together with fistula following
      laryngopharyngectomy) are presented. RESULTS: Because of protracted and
      complicated wound healing HBO was applied in all three cases, eventually leading
      to very satisfying subconsequent wound-healing. In connection with these cases,
      the underlying problems and the effects of HBO are discussed. SUMMARIZING: The
      authors conclude, that HBO primary clinical application in treatment of
      problematic wound healing in head and neck appears to be very effective and
      helpful and should not be underrated whilst discussing this therapy in different
      contexts.

PMID- 10911606
TI  - [Recurrent laryngeal nerve paralysis after thyroidectomy].
AB  - AIM: The paper's aim is to examine and analyse the incidence rate of
      postoperative pareses of N. recurrens in 1311 operated thyroid sides and 909
      patients. PATIENTS AND SURGICAL TECHNIQUE: In histology we found nodular changes
      in 92.6% of 840 operated benignant strumata. In 69 malignant strumata the
      papillary thyroid carcinoma was the most common. The surgical concept changed
      within the last years from subtotal resections and enuclations to functional and
      total resections. RESULTS: Preoperative pareses of N. recurrens were seen in 5.3%
      of the patients, which emphasizes the demand for a preoperative laryngologic
      examination. Surgery on relapsed benignant strumata were followed by permanent
      unilateral pareses of N. recurrens in 9.9%, surgery on malignant strumata in 7.5%
      of the cases. After surgery of relapsed malignant strumata we found 2 permanent
      pareses in 21 reoperated thyroid sides. During a regular follow-up over the
      period of 12 months at least, we saw 22 transitory pareses of N. recurrens, which
      corresponds to a reversibility rate of 35%. In first surgical interventions with
      benignant histology the reversibility rate was 49%. Depending on first or relapse
      surgery, the histological findings and chosen surgical method the rate of
      permanent unilateral pareses of N. recurrens was only 1.7% in relation to the
      first time operated sides of benignant strumata.

PMID- 10911608
TI  - [Interesting case no. 34. Soft tissue emphysema of the neck after pressurized air
      insufflation].

PMID- 10911609
TI  - [Plastic reconstruction of the neck area].

PMID- 10911610
TI  - Restriction primers as short as 6-mers for PCR amplification of bacterial and
      plant genomic DNA and plant viral RNA.
AB  - Amplification of DNA or RNA sequences using the polymerase chain reaction (PCR)
      or reverse transcriptase PCR (RT-PCR) requires primers of an appropriate length
      to be designed. Two hexamer restriction primers, denoted as E101 and H301, which
      correspond to sequences of EcoRI and HindIII recognition sites, respectively,
      were selected and used as primers in PCR and RT-PCR. We first applied the
      restriction primers to the plasmid DNA and bacterial (Pseudomonas) and plant
      (Cymbidium) genomic DNAs. We observed positive DNA amplifications with the
      recombinant plasmid DNA and bacterial and plant genomic DNAs. Purified viral RNA
      was used for template in the RT-PCR with the primers and successful DNA
      amplification was obtained. These results suggest that the 6-mer restriction
      primers can be useful for new applications in PCR.

PMID- 10911611
TI  - Small, efficient hammerhead ribozymes.
AB  - The hammerhead ribozyme is able to cleave RNA in a sequence-specific manner.
      These ribozymes are usually designed with four basepairs in helix II, and with
      equal numbers of nucleotides in the 5' and 3' hybridizing arms that bind the RNA
      substrate on either side of the cleavage site. Here guidelines are given for
      redesigning the ribozyme so that it is small, but retains efficient cleavage
      activity. First, the ribozyme may be reduced in size by shortening the 5' arm of
      the ribozyme to five or six nucleotides; for these ribozymes, cleavage of short
      substrates is maximal. Second, the internal double-helix of the ribozyme (helix
      II) may be shortened to one or no basepairs, forming a miniribozyme or minizyme,
      respectively. The sequence of the shortened helix + loop II greatly affects
      cleavage rates. With eight or more nucleotides in both the 5' and the 3' arms of
      a miniribozyme containing an optimized sequence for helix + loop II, cleavage
      rates of short substrates are greater than for analogous ribozymes possessing a
      longer helix II. Cleavage of gene-length RNA substrates may be best achieved by
      miniribozymes.

PMID- 10911612
TI  - Sequence analysis and tissue specific expression of human HOXA7.
AB  - A 3071-bp fragment containing the human HOXA7 gene was sequenced. It contained
      two exons, one intron, and two polyadenylation signals (AATAAA) at positions 1844
      and 2923. The exon encoded 230 aa residues, while the hexapeptide, homeodomain,
      and C-terminal acidic domains were detected. When the total sequences were
      compared with those of murine Hoxa-7, the 5' untranslated region (UTR), exon I,
      intron, exon II, and 3' UTR exhibited 99, 92, 65, 85, and 72% homology,
      respectively. Through Northern analysis, about a 1.9-kb transcript was detected
      in the fetal kidney. Minor transcripts of 1.5 and 1.1-kb were also detected in
      the fetal liver as well as in the kidney. In the case of adult tissues, most of
      the tissues tested (lung, liver, skeletal muscle, kidney, pancreas, and
      placenta), except brain tissue, expressed a 5.3 kb transcript with various
      intensities. Our results here suggested that not only Abd-B type Hox genes, but
      the ones in paralogous groups I-VIII could generate multiple transcripts. The
      characterization of these tissue-specific and stage-specific alternative
      transcripts would help to understand the regulatory function of the HOXA7 gene
      during development, and possibly the pathology of human disease caused by Hox
      genes.

PMID- 10911613
TI  - The use of site-directed mutagenesis, transient transfection, and radioligand
      binding. A method for the characterization of receptor-ligand interactions.
AB  - Receptor-ligand interactions have traditionally been evaluated using a number of
      biochemical techniques including radioligand binding, photoaffinity labeling,
      crosslinking, and chemical modification. In modern biochemistry, these approaches
      have largely been superseded by site-directed mutagenesis in the study of protein
      function, owing in part to a better understanding of the chemical properties of
      oligonucleotides and to the ease with which mutant clones can now be generated.
      The Altered Sites II in vitro Mutagenesis System from the Promega Corporation
      employs oligonucleotides containing two mismatches to introduce specific
      nucleotide substitutions in the nucleic acid sequence of a target DNA. One of
      these mismatches will alter the primary sequence of a given protein, whereas the
      second will give rise to a silent restriction site that is used to screen for
      mutants. Transient transfection of tsA201 cells with mutant cDNA constructs using
      calcium phosphate as a carrier for plasmid DNA permits expression of recombinant
      receptors that can be characterized using radioligand binding assays. In this
      article, we focus on site-directed mutagenesis, heterologous expression in
      eukaryotic cells, and radioligand binding as a methodology to enable the
      characterization of receptor-ligand interactions.

PMID- 10911614
TI  - Absolute quantification of human chorionic gonadotropin-beta mRNA with TaqMan
      detection. 4.
AB  - We describe a reverse transcriptase-polymerase chain reaction (RT-PCR) for
      determination of human chorionic gonadotropin-beta (HCG beta) mRNA copies using
      the TaqMan system. To evaluate our quantitative assay, we analyzed HCG beta
      transcripts of all protein coding genes (HCG beta 5, 3, 8, and 7) in human RNA
      panels of different normal tissues and in glycodelin-A-stimulated trophoblast
      cell cultures. Absolute quantification using HCG beta TaqMan probe was found to
      be highly reproducible. Our study of RNA panels confirms recently published
      results that expression of HCG beta transcripts is a common feature of a great
      variety of different normal tissues. High levels of HCG beta mRNAs (> 1,000
      molecules per 200 ng RNA) were detected in placenta, uterus, and testis. An
      increase of HCG beta mRNA expression (1.7-fold) was detected at 150 micrograms/mL
      glycodelin-A treatment in trophoblast cell culture. Time-dependence study showed
      that the increase in HCG beta mRNA level was evident at 60 min after glycodelin-A
      treatment. In summary, we have developed a highly sensitive one-tube, one-enzyme
      quantitative RT-PCR system that is time-saving and avoids postamplification
      procedures.

PMID- 10911616
TI  - Gradient temperature hybridization using a thermocycler for RNase protection
      assays.
AB  - The RNase protection assay (RPA) is a sensitive and quantitative assay for the
      detection of specific RNAs. Because some probes require an optimal temperature
      for efficient hybridization to the target RNAs, preliminary experiments to
      determine the optimal temperatures have to be done empirically, a process that is
      laborious and time-consuming. In order to simplify this process, a new gradient
      temperature hybridization procedure has been developed with the use of a
      thermocycler. This procedure eliminates the need for preliminary experiments to
      determine the optimal temperature of hybridization for a given probe.

PMID- 10911617
TI  - The application of databases and PCR in the cloning of glycosidase genes from the
      protozoan Tritrichomonas foetus.
AB  - Conserved sequence amplification (CSA) has been used to obtain sequence data for
      two glycosidase genes from the primitive eukaryote Tritrichomonas foetus. Few
      genes have been cloned from this organism, and there is little information
      concerning protein sequence. CSA is reliant on the use of database searches to
      identify short sequences of 3-9 amino acids conserved within a protein across a
      wide range of species. PCR primers are then constructed based on this sequence
      data and the DNA is amplified and sequenced. In the case of the beta
      galactosidase gene, N-terminal amino acid sequence data were used to construct a
      primer that replaced the upstream primer to ensure the amplified product was
      related to beta-D-galactosidase. CSA was also applied to the gene encoding the
      enzyme beta-N-acetyl-D-glucosaminidase from T. foetus, but in this case a segment
      of DNA was amplified, which, if correct, should contain a third conserved motif.
      The products of the CSA were sequenced, and the data obtained were compared to
      data in the SwissProt database. The results obtained suggest that this approach
      is useful for the cloning of genes to obtain novel sequence data from organisms
      where little genetic information is available.

PMID- 10911615
TI  - Ribozyme as an approach for growth suppression of human pancreatic cancer.
AB  - Ribozymes (catalytic RNAs, RNA enzymes) are effective modulators of gene
      expression because of their simple structure, site-specific cleavage activity,
      and catalytic potential, and have potentially important implications for cancer
      gene therapy. Point mutations in the K-ras oncogene are found in approx 90% of
      human pancreatic carcinomas, and can be used as potential targets for specific
      ribozyme-mediated reversal of the malignant phenotype. In this study, we focused
      on in vitro manipulation of ribozyme targeting of the mutated K-ras oncogene in a
      human pancreatic carcinoma cell line. We evaluated the efficacy of an anti-K-ras
      hammerhead ribozyme targeted against GUU-mutated codon 12 of the K-ras gene in
      cultured pancreatic carcinoma cell lines. The anti-K-ras ribozyme significantly
      reduced cellular K-ras mRNA level (GUU-mutated codon 12) when the ribozyme was
      transfected into the Capan-1 pancreatic carcinoma cells. The ribozyme inhibited
      proliferation of the transfected Capan-1 cells. These results suggested that this
      ribozyme is capable of reversing the malignant phenotype in human pancreatic
      carcinoma cells.

PMID- 10911619
TI  - Automated DNA mutation analysis by single-strand conformation polymorphism using
      capillary electrophoresis with laser-induced fluorescence detection.
AB  - Automation is essential for rapid genetic-based mutation analysis in clinical
      laboratory to screen a large number of DNA samples. We propose in this report an
      automatic process using Beckman Coulter P/ACE capillary electrophoresis (CE) with
      laser-induced fluorescence (LIF) system to detect a single-point mutation in the
      codon 12 of human K-ras gene. Polymerase chain reaction (PCR) using a
      fluorescently labeled reverse primer and a plain forward primer to specifically
      amplify a selected 50 bp DNA fragment in human K-ras gene. The amplified DNA is
      placed on the sample tray of the CE system with a pre-programmed step for single
      strand conformation polymorphism (SSCP) analysis. Sample injection and
      denaturation processes are performed online along with separation and real-time
      data analysis. The concept of automation for rapid DNA mutation analysis using CE
      LIF system for SSCP is presented.

PMID- 10911618
TI  - Rapid screening for putative exported proteins from Staphylococcus aureus using
      alkaline phosphatase as a reporter molecule.
AB  - Staphylococcus aureus causes a wide range of infections in humans, ranging from
      superficial skin infections to the more serious toxin-mediated diseases such as
      toxic shock syndrome. Owing to the increasing resistance of this bacterium to a
      wide range of antibiotics, the need to determine the virulence factors involved
      in infection is becoming more important as these molecules are potential
      therapeutic targets. In this study, we have screened for putative exported
      proteins from S. aureus on the basis that these proteins are likely to be the
      first point of contact between the bacterium and host during infection. We have
      constructed gene fusions between S. aureus DNA and a truncated version of the
      Escherichia coli phoA gene, and we report on the characterization of the
      recombinants exhibiting alkaline phosphatase activity. As well as known S. aureus
      proteins, we have identified a number of putative open reading frames that encode
      proteins similar to those from nonstaphylococcal species and also unique proteins
      that do not have any homologues on the current databases.

PMID- 10911620
TI  - A yeast genetic assay for caspase cleavage of the amyloid-beta precursor protein.
AB  - A functional assay for proteolytic processing of the amyloid precursor protein
      (APP) was set up in yeast. This consisted of a membrane-bound chimeric protein
      containing the beta-secretase cleaved C-terminal fragment of APP fused to the
      Ga14 transcription factor. Using this chimera in a GAL-reporter yeast strain, an
      expression library of human cDNAs was screened for clones that could activate the
      GAL-reporter genes by proteolytic processing of the membrane-bound APP-Gal4. Two
      human proteases, caspase-3 and caspase-8, were identified and confirmed to act by
      a mechanism that involved proteolysis at the site in the APP-Gal4 chimera that
      corresponded to the natural caspase cleavage site in APP, thus linking a readily
      scorable phenotype to proteolytic processing of APP. The activation of caspase-3
      involved a mechanism that was independent of aspartic acid residue 175 at the
      cleavage site normally required for processing of caspase-3.

PMID- 10911621
TI  - Generation of a ribozyme-adenoviral vector against K-ras mutant human lung cancer
      cells.
AB  - ras mutations represent one of the most common oncogenetic lesions in human non
      small cell lung cancer (NSCLC) and adversely affect the survival of patients
      afflicted with this disease. ras-directed gene therapy in the past employed
      primarily antisense oligonucleotides (AS-ODN) or expression vectors (such as a
      viral vector construct) that deliver the antisense sequence to inactivate the
      mutant oncogene message. These approaches produced minimal toxicity, and yet were
      limited in efficacy. Ribozymes present a viable alternative in antisense therapy
      by virtue of their renewable catalytic capability for site-specific RNA cleavage.
      We recently produced an adenoviral vector with a hammerhead ribozyme transgene
      (KRbz) that is specific for the K-ras codon 12 mutant sequence GUU, given the
      considerations that (a) in the United States, approx 30% of human NSCLCs express
      K-ras oncogene mutations, nearly all of which reside in codon 12; (b) anti-K-ras,
      anti-H, as well as anti-N-ras hammerhead ribozymes are potent growth inhibitors
      in various human cancers tested; and (c) in vitro and animal model studies
      suggest that ribozymes directed at oncogene (K- and H-ras C-fos, BCR-ABL) or
      human immunodeficiency viral gene messages are more effective than their
      antisense counterpart. This article describes the techniques involved in the
      production of the KRbz-adenoviral vector that is specific for the K-ras mutation
      GTT, and summarizes its in vivo antitumor effect against NSCLC xenografts
      expressing the relevant K-ras mutation in athymic mice.

PMID- 10911622
TI  - Expression and purification of recombinant proteins by fusion to maltose-binding
      protein.
AB  - The pMAL vectors provide a method for purifying proteins from cloned genes by
      fusing them to maltose-binding protein (MBP, product of malE), which binds to
      amylose. The vectors use the tac promoter and the translation initiation signals
      of MBP to give high-level expression of the fusion, and an affinity purification
      for MBP to isolate the fusion protein. The pMAL polylinkers carry restriction
      sites to insert the gene of interest, and encode a site for a specific protease
      to separate MBP from the target protein after purification. Vectors with or
      without the malE signal sequence can be used, to express the protein
      cytoplasmically for the highest level of production or periplasmically to help in
      proper folding of disulfide-bonded proteins.

PMID- 10911623
TI  - Semiquantitative immunoblots of membrane protein-epidermal growth factor.
AB  - Membrane proteins or cytokines are sometimes difficult to isolate and purify. Our
      group recently concentrated on epidermal growth factor (EGF) protein expression
      studies. Mature EGF was initially identified from mouse submaxillary gland
      extract as a stimulator of eyelid opening and incisor eruption when injected into
      newborn mice and rats. The EGF precursor is a transmembrane protein with eight
      additional EGF-like repeats. Our previous study has shown that the EGF precursor
      without these eight EGF-like repeats (hEGF) was biologically active. Here, we
      introduce a modified method for rapid detection of hEGF. The membranous protein
      was directly extracted from various organs of transgenic mice (including the
      submandibular gland, kidney, liver, heart, and testis) with two different buffers
      and easily detected by semiquantitative immunoblotting.

PMID- 10911624
TI  - Detecting and minimizing glycosidase activities that can hydrolyze sugars from
      cell culture-produced glycoproteins.
AB  - Heterogeneity of cell culture-produced glycoproteins often results from the
      presence or absence of a few sugars found on the terminus of glycoprotein
      oligosaccharides. Variability in bioprocess factors can potentially lead to
      variability in this oligosaccharide heterogeneity (1). Although stochastic events
      in the intracellular biosynthetic process have long been recognized as a cause of
      oligosaccharide heterogeneity (2), more recent data has demonstrated that
      extracellular degradation by glycosidases can also contribute to oligosaccharide
      heterogeneity (3,4). The purpose of this chapter is to introduce the concept and
      consequence of glycosidase degradation, to discuss methods for evaluating whether
      glycosidase degradation is significant for a particular process, and to provide
      some potential remedies to alleviate undesirable degradation.

PMID- 10911625
TI  - Comparison of two kinds of methods to determine the titer of recombinant
      retrovirus containing beta-globin gene based on G418 selection.
AB  - Four recombinant retrovirus (RV) vectors containing human beta-globin gene and
      regulatory elements were constructed. To determine the titers of recombinant RV
      from corresponding producer cell lines, we compared two kinds of method (the
      simple and the conventional) based on G418 resistance, which is conferred by neo
      gene of RV vector. The results demonstrated that the simple method shortened the
      selection period to 3 d instead of 10-12 d with the conventional method and
      reduced the amount of work; importantly, the titers determined by the simple
      method were not different significantly from those measured by the conventional
      method. It can be concluded that the simple method can be used to determine the
      titers of recombinant RV containing not only cDNA but also genomic DNA with
      introns and complex regulatory elements instead of the conventional method.

PMID- 10911627
TI  - Allergic rhinitis and asthma: linking upper and lower airway disorders.

PMID- 10911626
TI  - How are allergic rhinitis and sinusitis connected with asthma?

PMID- 10911628
TI  - The association between allergic rhinitis and asthma in children and adolescents:
      epidemiologic considerations.

PMID- 10911629
TI  - A pathophysiologic link between allergic rhinitis and asthma.

PMID- 10911630
TI  - Treatment of allergic rhinitis with antihistamines and decongestants and their
      effects on the lower airway.

PMID- 10911631
TI  - Treatment of allergic rhinitis with intranasal steroids and their effects on the
      lower airway.

PMID- 10911632
TI  - Specific allergen immunotherapy for allergic rhinitis and asthma.

PMID- 10911633
TI  - Sinusitis and pediatric asthma.

PMID- 10911634
TI  - Quality-of-life outcomes measures of asthma and allergic rhinitis.

PMID- 10911635
TI  - The Vicenza Peritoneal Dialysis Course: from origin to the new millennium.

PMID- 10911636
TI  - Effects of osmotic agents upon the in vivo exposed mesothelial monolayer.

PMID- 10911638
TI  - Neoangiogenesis in the peritoneal membrane.
AB  - OBJECTIVE: This study reviews relevant publications on the peritoneal vasculature
      and tries to establish morphological-functional relationships. DESIGN: The design
      is a review article. RESULTS: Recent morphological studies in peritoneal dialysis
      (PD) patients have shown the presence of diabetiform neoangiogenesis in long-term
      peritoneal dialysis. The same abnormalities could be induced in rats administered
      a high glucose dialysis solution daily for 20 weeks. The animals showed
      functional abnormalities in peritoneal transport similar to those found in long
      term PD patients. Evidence was obtained in patients that vascular endothelial
      growth factor could be involved in glucose-induced peritoneal neoangiogenesis.
      CONCLUSIONS: Diabetiform peritoneal neoangiogenesis is an important pathogenetic
      factor in ultrafiltration failure in long-term peritoneal dialysis patients.

PMID- 10911637
TI  - Effect of high glucose on peritoneal mesothelial cell biology.
AB  - OBJECTIVE: This study reviews evidence that implicates high glucose (HG) in the
      pathogenesis of peritoneal fibrosis and proposes mechanisms potentially involved
      in the HG-induced peritoneal fibrosis that is observed in long-term peritoneal
      dialysis (PD) patients. DESIGN: Selected Western literature is reviewed,
      examining the effect of HG on rat or human peritoneal mesothelial cell (HPMC)
      biology with particular reference to extracellular matrix (ECM) gene expression
      and protein synthesis. RESULTS: HG up-regulated the expression of monocyte
      chemotactic peptide-1 (MCP-1), transforming growth factor beta 1 (TGF beta 1),
      and fibronectin messenger RNAs (mRNAs) and proteins. These HG-induced up
      regulations were effectively blocked by the inhibition of protein kinase C (PKC).
      In addition, cytosolic reactive oxygen species (ROS) rapidly increased in HPMC
      cultured under HG, and treatment with antioxidant effectively inhibited HG
      induced fibronectin protein synthesis by HPMC. CONCLUSION: Continuous exposure of
      the peritoneal membrane to HG may induce changes in HPMC biology, leading to
      excessive deposition of ECM and peritoneal injury. HG-induced activation of
      diacylglycerol PKC (DAG-PKC) plays a major role in up-regulation of MCP-1, TGF
      beta 1, and fibronectin synthesis by HPMC cultured under HG. In addition, ROS,
      recently recognized as signalling molecules, are rapidly generated in HPMC as a
      result of increased glucose metabolism and may prove to be an important mediator
      of HG-induced peritoneal injury.

PMID- 10911639
TI  - Chemistry of glucose and biochemical pathways of biological interest.
AB  - Glucose degradation, yielding GDPs, can take place in vivo or during heat
      treatment of glucose solutions. AGEs are formed from the interaction of D-glucose
      with reactive amino-acid side chains of proteins. Both GDPs and AGEs have been
      shown to impair cellular function. GDPs have additional damaging effects because
      they strongly promote AGE formation (as compared to D-glucose).

PMID- 10911640
TI  - Glucose degradation products: relationship with cell damage.

PMID- 10911641
TI  - Strategies to reduce glucose exposure in peritoneal dialysis patients.
AB  - Glucose has been used successfully for more than two decades in peritoneal
      dialysis, and in this regard, must be considered a safe and effective osmotic
      agent. Recently, however, insight has been growing about the potential for
      metabolic and peritoneal effects arising from long-term exposure to high glucose
      concentrations--for example, hyperlipidemia and loss of peritoneal
      ultrafiltration. Clinical concerns over exposure to excessive glucose and glucose
      degradation products (GDPs) during peritoneal dialysis can be significantly
      ameliorated by the use of non-glucose-based peritoneal dialysis (PD) solutions,
      in combination with more biocompatible glucose-based formulations. Peritoneal
      exposure to GDPs can be reduced by using low-GDP-containing glucose formulations
      and non glucose solutions such as amino acids and icodextrin. Peritoneal glucose
      exposure, hyperosmolar stress, and carbohydrate absorption can be reduced by
      using a combination of icodextrin and amino acids.

PMID- 10911642
TI  - Lactate-buffered and bicarbonate-buffered solutions with less glucose degradation
      products in a two-chamber system.

PMID- 10911643
TI  - Can we prevent the degradation of glucose in peritoneal dialysis solutions?

PMID- 10911644
TI  - The dialysis outcomes quality initiative guidelines: a new standard for
      everybody?

PMID- 10911645
TI  - Urea is the best molecule to target adequacy of peritoneal dialysis.
AB  - For hemodialysis, a large base of data shows the validity of modelling the
      dialysis dose and reliably estimating protein intake from equilibrated Kt/V urea
      (eKt/VU), the total dialyzer urea clearance provided during each treatment
      divided by the urea distribution volume. An eKt/VU of 1.05 thrice weekly is
      judged adequate, but is still under study. In continuous ambulatory peritoneal
      dialysis (CAPD), two dosage criteria are widely recognized: continuous
      ("standard") Kt/VU (stdKt/VU = 2.0 weekly), and total creatinine (Cr) clearance
      normalized to body surface area (KCrT = 70 L/week/1.73 m2). The CANUSA study
      concluded that a stdKt/VU of 2.1 and a KCrT of 70 L/week/1.73 m2 gave equivalent
      clinical outcomes. The Dialysis Outcomes Quality Initiative (DOQI) recommends
      values of 2.0 and 60 L/week/1.73 m2 respectively. An analysis of these two
      parameters for males and females over a wide range of body surface areas (BSAs)
      was done and the analysis showed: (1) The U and Cr dose criteria are
      incommensurable--that is, they can virtually never be achieved simultaneously in
      anephric patients. (2) The Cr criterion varies widely with the sex of the patient
      and with the BSA-dependent variation in stdKt/VU over a range of 2.1 to 3.0. (3)
      The U criterion always produces a KCrT < 60 L/week/1.73 m2 in females and 60-70
      L/week/1.73 m2 in males. With respect to U and Cr, the CANUSA results were
      concluded to be valid in patients with substantial residual renal function, but
      probably not applicable to anephric patients where the doses are clearly
      incommensurable.

PMID- 10911646
TI  - Creatinine is the best molecule to target adequacy of peritoneal dialysis.
AB  - The overall conclusion is that neither creatinine clearance nor urea clearance is
      the perfect index for predicting outcome in PD patients. In the absence of
      indices that are better validated and more convenient, creatinine and urea are
      what we have to use. They are best seen as two imperfect, but potentially
      complementary, measurements. On balance, creatinine clearance is the better of
      the two indices, in that it gives greater weight to residual renal function, and
      residual renal function is probably a stronger predictor of patient outcome than
      peritoneal clearance per se. However, creatinine clearance has a particular
      weakness in low transporters; values have to be interpreted with discretion in
      this group. Furthermore, both indices are flawed because of the manner in which
      they are conventionally normalized. Research into more appropriate methods of
      normalization, or into whether normalization is required at all, would be
      helpful. The complex relationship between these clearance indices, protein
      intake, and lean body mass also needs to be kept in mind. While this paper argues
      in favour of creatinine clearance as the better index, it still suggests that
      both indices be used, together with a large measure of clinical judgment.

PMID- 10911647
TI  - Automated peritoneal dialysis: clinical prescription and technology.

PMID- 10911648
TI  - Solute kinetics in automated peritoneal dialysis.

PMID- 10911650
TI  - Nightly intermittent peritoneal dialysis: targets and prescriptions.
AB  - Adequate peritoneal dialysis can be achieved in most ESRD patients, provided that
      the prescription is individualized according to body surface area, body weight,
      residual renal function, and peritoneal transport characteristics. NIPD is
      particularly indicated in patients with significant residual renal function or
      those with a high-transport peritoneal membrane (accounting for about 10% of the
      PD patient population). "Dry day" NIPD reduces small-solute clearance by at least
      10%-15% and middle-molecule clearance by almost 50%. Thus, most NIPD patients
      without residual renal function are at risk of inadequate treatment. The target
      dose of NIPD should be a weekly Kt/V of at least 2.2 and a weekly total
      creatinine clearance of 66 L/1.73 m2. However, the periodic clinical evaluation
      of patients should have priority over the mere achievement of a numerical
      clearance target.

PMID- 10911649
TI  - Optimization of fill volumes in automated peritoneal dialysis.

PMID- 10911651
TI  - Continuous cycling peritoneal dialysis, PD plus, and high-flow automated
      peritoneal dialysis: a spectrum of therapies.

PMID- 10911652
TI  - Advantages of tidal peritoneal dialysis.
AB  - Tidal peritoneal dialysis (TPD) was introduced in 1990 in the hopes of improving
      dialysis efficiency. Studies comparing low dialysate flow rates show that tidal
      peritoneal dialysis has no clearance advantage over intermittent peritoneal
      dialysis (IPD). With high dialysate flow rates, TPD may be superior or similar to
      IPD in efficacy, but it is expensive because of the high volumes of dialysis
      solution used. However, it provides better fluid flow mechanics and more comfort
      to the patient owing to fewer alarms and less pain during inflow and outflow.

PMID- 10911653
TI  - Sodium balance in automated peritoneal dialysis.

PMID- 10911654
TI  - Assessment of the effectiveness, safety, and biocompatibility of icodextrin in
      automated peritoneal dialysis. The Dextrin in APD in Amsterdam (DIANA) Group.
AB  - OBJECTIVE: Our study assessed the efficacy, safety, and biocompatibility of
      icodextrin (I) solution compared to glucose (G) solution as the daytime dwell in
      continuous cycling peritoneal dialysis (CCPD). DESIGN: In a randomized, open,
      prospective, parallel group study of two year's duration, either I or G was used
      for the long daytime dwell in CCPD patients. METHOD: The study was carried out in
      a university hospital and teaching hospital. Established CCPD patients and
      patients new to the modality were both included. Clinic visits were made at three
      month intervals. In all patients, clinical data were gathered; ultrafiltration
      (UF) was recorded; and serum, urine, and dialysate samples and effluents were
      collected. Peritoneal defense characteristics and mesothelial markers were
      determined. Every six months, peritoneal kinetics studies were performed, and
      serum samples for icodextrin metabolites were taken. RESULTS: Thirty-eight
      patients (19 G, 19 I) started the study. The median follow-up was 16 months and
      17 months respectively (range: 0.5 - 26 months and 3 - 26 months, respectively).
      Daytime UF volumes increased significantly (p < 0.001), and 24-hour UF tended to
      increase from baseline in the I group. Dialysate creatinine clearance increased
      non significantly in both groups over time. In I patients, serum disaccharides
      (maltose) concentration increased from 0.05+/-0.01 mg/mL [mean+/- standard error
      of mean (SEM)] at baseline, to an average concentration in the follow-up visits
      of 1.15+/- 0.04 mg/mL (p <0.001). At the same time, serum sodium levels decreased
      from 138.1 +/- 0.7 mmol/L to an average concentration in the follow-up visits of
      135.9 +/- 0.8 mmol/L (p < 0.050). At 12 months, the serum sodium concentration
      increased to a non significant difference from baseline. Serum osmolality
      increased, but did not differ significantly from G users at any visit. During
      peritonitis (P), daytime dwell UF decreased significantly compared to non
      peritonitis (NP) episodes in G patients (p < 0.0 01), but remained stable in I
      patients. Total 24-hour UF also decreased in G patients (p < 0.001), but not in I
      patients. In these I patients, serum disaccharides increased from 0.05 +/- 0.01
      mg/mL to 1.26 +/- 0.2 mg/mL during follow-up. During peritonitis, serum
      disaccharides concentration did not increase further (1.47 +/- 0.2 mg/mL, p=
      0.56). Thirty P episodes occurred during follow-up: 16 in G patients and 14 in I
      patients (1 per 17.6 months and 1 per 21.9 months, respectively.) After one year,
      absolute number and percentage of effluent peritoneal macrophages (PM phi s) were
      significantly higher in I patients than in G patients. The difference in
      percentage persisted after two years. The phagocytic capacity of PM phi s
      decreased over time, resulting in a borderline significant difference for
      coagulase-negative staphylococci phagocytosis (p=0.005) and a significant
      difference for E. coli phagocytosis (p <0.05) in favor of I patients. PM phi
      oxidative metabolism, PM phi cytokine production, and effluent opsonic capacity
      remained stable over time with no difference between the groups. Mass transfer
      area coefficients (MTACs) and clearances were stable and appeared unaffected by G
      or I treatment. Effluent cancer antigen 125 (CA125) was stable in G users and
      tended to decrease in I users. Effluent interleukin-8 (IL-8), carboxy-terminal
      propeptide of type I procollagen (PICP ), and amino-terminal propeptide of type
      III procollagen (PIIINP) did not change over time and did not differ between the
      groups. CONCLUSION: The use of I for the long daytime dwell in CCPD led to an
      increase in total UF of at least 261 mL per day, which was maintained over at
      least 24 months. During I treatment, serum I metabolites increased significantly
      and serum sodium concentrations decreased initially. As a result, serum
      osmolality increased slightly. Clinical adverse effects did not accompany these
      findings. The UF gain in the I patients was even higher during P, without a

PMID- 10911655
TI  - Description and clinical outcomes of peritoneal dialysis: analyses from the
      United States Renal Data System.
AB  - USRDS studies provide results that are consistent when considering the effect of
      time since the onset of ESRD in comparisons of PD and HD outcomes. The results
      are representative of patient selection and practice in the U.S., but may not
      apply in other countries, where patients are selected to PD using very different
      criteria. In international comparisons, even adjustment for comorbid conditions
      may not fully compensate for selection. The analytical experience from the USRDS
      may serve as a model for similar analyses in environments where different
      practices and registries are used.

PMID- 10911656
TI  - The European Registry: where do we stand?

PMID- 10911657
TI  - Long-term peritoneal dialysis outcome in a single center.

PMID- 10911658
TI  - Patients on chronic peritoneal dialysis for ten years or more in North America.
AB  - Thirty-six patients on peritoneal dialysis (PD) for more than ten years in six
      North American centers were analyzed retrospectively. In the six centers, the
      percentage of patients surviving for more than ten years varied between 0.8% and
      7.3%. The study group included 27 females and 9 males aged 38.6 +/- 14.2 years
      [mean +/- standard deviation (SD)] at the start of treatment. Of the 36 patients,
      28 were Caucasian. The most common cause of end-stage renal disease (ESRD),
      present in 12 patients, was chronic glomerulonephritis. Only 4 patients had
      diabetes. At the beginning of the study, 19 patients had hypertension (the most
      common comorbid condition); 11 had no comorbid conditions at the start.
      Creatinine clearance at the start was 4.12 +/- 3.5 mL per minute, and the mean
      duration to anuria was 51 +/- 25 months. Mean initial body weight was 55 +/- 9
      kg, and mean body surface area was 1.5 +/- 0.2 m2. Serum albumin levels showed an
      increase from 33.8 +/- 3.6 g/L at the start of the study to 38.2 +/- 3.9 g/L at
      the end. Hospitalization rate was low at 0.5 +/- 0.3 admissions per patient-year,
      and duration of hospitalization was 4.8 +/- 3.7 days per patient-year.
      Peritonitis was the most common cause of hospitalization. The mean peritonitis
      rate was 1 episode every 52 +/- 48 patient-months. There were 36 catheter changes
      in 18 patients; 16 patients had a single PD catheter throughout the period of
      study. Autonomous hyperparathyroidism was the most common long-term complication.
      At the end of the study period, 11 patients were still on PD, 9 had died, 5 had
      been transferred to hemodialysis (HD), 1 was alive with a functioning allograft,
      and 1 was lost to follow-up. We conclude that patients who survive longer than
      ten years on PD are most likely to be young Caucasian females, small in body
      size, who are non diabetic, with few comorbid conditions. These long-term
      survivors have few hospitalizations, and their peritonitis rate is low. In this
      group of patients, severe autonomous hyperparathyroidism is the most common long
      term complication.

PMID- 10911659
TI  - The role of peritoneal dialysis as first modality in an integrative approach to
      patients with end-stage renal disease.

PMID- 10911660
TI  - Initiation of dialysis: current trends and the case for timely initiation.

PMID- 10911661
TI  - L-carnitine and peritoneal dialysis.

PMID- 10911662
TI  - Major and minor risk factors for cardiovascular disease in peritoneal dialysis.
AB  - All uremic patients have multiple risk factors for CAD including in many, the
      conditions that caused their ESRD--for example, diabetes and hypertension.
      conventional risk factors--for example, dyslipidemia and hyperhomocysteinemia.
      risk factors that are unique to uremia--for example, calcium and phosphate
      abnormalities. PD patients have particular risk with respect to their lipid
      status and hyperinsulinemia. Many of these risks are potentially modifiable, but
      evidence does not exist to assess the impact of treatment on clinical outcomes.
      Therefore, current decisions for therapy directed at risk factor modification
      must be made on an individual basis.

PMID- 10911663
TI  - Management of high peritoneal transporters.
AB  - High transporters on chronic peritoneal dialysis are challenged by increased
      protein losses, high glucose absorption with associated metabolic abnormalities,
      and poor ultrafiltration. Furthermore, the relative risk of mortality and
      technique failure is higher in high transporters than in patients of other
      transport types. An approach for satisfactory management of such patients on
      peritoneal dialysis (PD) has not been clearly demonstrated.

PMID- 10911664
TI  - Use of amino acids in peritoneal dialysis solutions.

PMID- 10911665
TI  - Continuous-flow peritoneal dialysis.

PMID- 10911666
TI  - Erythropoietin therapy in peritoneal dialysis patients.

PMID- 10911667
TI  - Environmental scan 2000: issues facing state mental health agencies.
AB  - With the new millennium, state mental health agencies (SMHAs) are facing a
      variety of new issues. In this article, the authors report on the changes in
      state mental health systems that have occurred during the 2 years between
      interviews conducted with directors of each SMHA. While issues such as managed
      care, the influence of state Medicaid waivers on the development of
      public/private partnerships, and federal welfare reform continued to be key
      concerns, directors are focusing more on other issues such as assessing SMHA
      operations, establishing linkages with other state health and human service
      agencies, and inculcating new knowledge, technologies, and model practices.

PMID- 10911668
TI  - Effect of antidepressant choice on the incidence and economic intensity of
      hospitalization among depressed individuals.
AB  - This study identified differences in hospital utilization for mental health
      problems among depressed patients initially treated with selective serotonin
      reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs). A retrospective
      sample of 2,557 patients was obtained from a private insurance claims database.
      Quasi-experimental, two-stage multivariate regression modeling was used to
      estimate the likelihood of hospitalization and subsequent inpatient expenditures.
      Only 2% of the sample were hospitalized, and the average expenditures per
      admitted patient was about $8,000. Patients initially prescribed sertraline had
      the same likelihood of hospitalization for a mental health problem as patients
      prescribed TCAs. Patients initially prescribed fluoxetine were half as likely to
      be hospitalized as patients initially prescribed TCAs. Once hospitalized, no
      differential effects of a specific antidepressant on inpatient expenditures were
      found.

PMID- 10911669
TI  - Private and public ownership in outpatient substance abuse treatment: do we have
      a two-tiered system?
AB  - As investor-owned organizations increase their presence in the mental health care
      sector, questions emerge regarding the effects of ownership type on service
      delivery. One important question is whether ownership is related to patient
      access to care for persons requiring treatment for substance abuse problems.
      Using data from a 1995 national survey of outpatient substance abuse treatment
      units, the authors investigate whether there are differences in measures of
      patient access to care among investor-owned, not-for-profit, and public provider
      organizations. Results indicate investor-owned units cater to and serve a
      clientele that differs from that of not-for-profit and public units, suggesting
      the presence of a two-tiered system of substance abuse treatment.

PMID- 10911670
TI  - Social skills training modules in an intensive community support program.
AB  - The authors describe a randomized control study that tested the effectiveness of
      social skills training modules as an adjunct to an assertive community treatment
      (ACT) program. Implementation of the modules in this context presented multiple
      logistic and organizational problems. Only 21 of the 42 demonstration clients
      completed all or part of one of two scheduled modules. Thus the modules were not
      effective because of characteristics of the modules themselves, the nature of the
      overall program, and the study design. An ACT/social skills-training alliance
      would be more likely to succeed if individually tailored interventions were used
      rather than or supplementing the curriculum-based modules.

PMID- 10911671
TI  - A survey of burnout among mental health center directors in a rural state.
AB  - The executive directors of all Iowa community mental health centers were surveyed
      in order to determine the relationship between work environment and job burnout.
      Organizational characteristics related to "rurality," i.e., location in a rural
      county, fewer employees, smaller budgets, and more time spent in direct clinical
      care, were not associated with burnout among directors in this rural state.
      Implications of the effect of service reorganization on burnout in human service
      providers in regard to rural health policy, work force issues, and directions for
      future research are discussed.

PMID- 10911672
TI  - Managing care and dollars in the 21st century: recommendations for community
      mental health systems of care.

PMID- 10911673
TI  - Applying nominal group method to needs identification in Hong Kong mental health
      services.

PMID- 10911674
TI  - The domain of hypnosis: a multifactorial model.
AB  - A conceptual framework is presented to help the reader understand some
      controversies in the hypnosis literature and a means of understanding some
      important differences and disagreements in the field. It is this author's view
      that hypnotic behavior can be understood as a complex mix of four conceptual (and
      empirical) independent dimensions: expectations, akin to the placebo response in
      clinical technique; suggestion; a cognitive component including relaxation,
      imagery in all modalities, and trance logic; dissociation, which is seen as the
      key component of deep hypnosis, and which may involve individual differences in
      the flexible control of experience.

PMID- 10911675
TI  - Clinical applications of hypnosis for brief and efficient pain management
      psychotherapy.
AB  - This paper describes four specific clinical applications of hypnosis that can
      make psychotherapy for pain management briefer, more goal-oriented, and more
      efficient: (1) the assessment of hypnotizability; (2) the induction of hypnotic
      analgesia and development of individualized pain coping strategies; (3) direct
      suggestion, cognitive reframing, hypnotic metaphors, and pain relief imagery; and
      (4) brief psychodynamic reprocessing during the trance state of emotional factors
      in the patient's experience of chronic pain. Important theoretical and clinical
      issues regarding the relationship of hypnotizability to the induction of hypnotic
      analgesia are presented, and attempts to individualize pain treatment strategies
      on the basis of assessed differences in hypnotizability and patients' preferred
      coping strategies are described. Some ways are also presented of integrating
      direct hypnotic suggestion, cognitive reframing, hypnotic metaphors and imagery
      for alleviating the sensory and affective components of pain with an exploratory,
      insight-oriented, and brief psychodynamic reprocessing approach during trance for
      resolving unconscious sources of resistance to treatment and reducing the
      emotional overlay associated with chronic pain. Some basic assumptions underlying
      the use of this approach are discussed, and a brief step-by-step protocol is
      outlined.

PMID- 10911676
TI  - Psychoneuroimmunology: an interpretation of experimental and case study evidence
      towards a paradigm for predictable results.
AB  - This paper surveys a number of key experiments and case studies relating to
      psychoneuroimmunology. It finds that most techniques to influence or even direct
      the immune system via the mind fall into a series of theoretical categories
      called passive, active and targeted effects. By examining the results of
      experiments and studies in the light of these categories a number of important
      conclusions are drawn. These conclusions explain differences in experimental
      results, describe those variables that appear to be central to obtaining results,
      and describe in detail where experimentation should be concentrated to further
      knowledge of psychoneuroimmunology.

PMID- 10911677
TI  - Binaural-beat induced theta EEG activity and hypnotic susceptibility.
AB  - Six participants varying in degree of hypnotizability (2 lows, 2 mediums, and 2
      highs) were exposed to 3 20-minute sessions of a binaural-beat sound stimulation
      protocol designed to enhance theta brainwave activity. The Stanford Hypnotic
      Susceptibility Scale, Form C (SHSS:C) was used for pre- and post-stimulus
      measures of hypnotic susceptibility. A time-series analysis was utilized to
      evaluate anterior theta activity in response to binaural-beat sound stimulation
      over baseline and stimulus sessions. The protocol designed to increase anterior
      theta activity resulted in a significant increase in percent theta for 5 of 6
      participants. Hypnotic susceptibility levels remained stable in the high
      susceptible group and increased significantly in the low and medium-susceptible
      groups.

PMID- 10911678
TI  - Relationship between QEEG relative power and hypnotic susceptibility.
AB  - The purpose of this study was to investigate the relationship between
      quantitative electroencephalograph relative amplitude, relative power and
      hypnotic susceptibility. Hypnotic susceptibility, measured by the Wickramasekera
      Experience Inventory, was found to be positively correlated with QEEG theta
      relative amplitude (r = 0.260, p < .10). In addition, hypnotic susceptibility was
      found to be negatively correlated with QEEG alpha relative amplitude (r = -.323,
      p < .05) and alpha relative power (r = -0.322, p < .05). These findings suggest
      that QEEG relative amplitude and QEEG relative power, as correlates of hypnotic
      susceptibility, may be a promising avenue for future research.

PMID- 10911679
TI  - Renal and ureteral surgery in dogs.
AB  - Renal and ureteral surgeries are performed commonly in veterinary medicine.
      Potential surgeries include nephrectomy, nephrotomy, pyelolithotomy,
      neoureterostomy, and ureteral anastomosis. The most common reason for surgery is
      the removal of urinary calculi. Before performing surgery, consideration of the
      patient's renal function is important to obtain optimal results. Maintaining
      normal urine production in the perioperative and postoperative period is
      important in most cases. The surgical procedures listed previously are reviewed
      individually, including postoperative care.

PMID- 10911680
TI  - Cystotomy, partial cystectomy, and tube cystostomy.
AB  - Knowledge of the regional anatomy and healing characteristics of the urinary
      bladder are crucial to successful surgical intervention in common disorders of
      the bladder. Innervation and blood supply enter the neck region of the bladder on
      the dorsal surface. Surgical approach to the bladder is via a ventral midline
      incision. Cystotomy is most commonly performed on the ventral surface of the
      bladder and the incision is closed using absorbable suture material in a single
      layer, appositional closure. Removal of urinary calculi is the most common
      indication for cystotomy and should be accompanied by mucosal biopsy and culture.
      After cystotomy for removal of calculi, a lateral radiograph should be made to
      confirm removal of all calculi. Partial cystectomy is indicated for bladder
      trauma, neoplasia, patent urachus, and urachal diverticula. A large percentage of
      the bladder wall can be excised with gradual return to near normal function when
      the trigone region is preserved. Complete cystectomy is not recommended because
      of the patient morbidity and client dissatisfaction with these procedures. Tube
      cystostomy is performed routinely for temporary or permanent urinary diversion.
      Temporary diversion may be performed concurrently with surgical repair of
      urethral trauma or to relieve acute urethral obstructions. Permanent cystostomy
      may be performed in cases of neurogenic bladder atony or bladder cancer.

PMID- 10911681
TI  - Diagnosis and surgical management of ectopic ureters.
AB  - Ureteral ectopia is a congenital abnormality of the terminal segment of one or
      both ureters in which the ureteral orifice is located distal to the trigone of
      the bladder. Continuous or intermittent urinary incontinence is the most
      frequently reported clinical symptom associated with ureteral ectopia. A variety
      of anatomic morphologies of ectopic ureters have been reported. Historically,
      surgical therapy focused on reestablishing drainage of the ureters into the
      bladder lumen. However, continued urinary incontinence after surgery is the most
      frequently reported complication. Specific classification and successful
      management of the various types of ectopic ureters remain diagnostic and
      therapeutic challenges to the veterinary clinician. Cystoscopic evaluation of the
      lower urinary tract and urodynamic evaluation of bladder and urethral function
      has improved the presurgical assessment of the patient. Surgical procedures,
      which are aimed at repositioning the ureteral orifice(s) within the bladder lumen
      and treating primary sphincter incompetence, are necessary to successfully manage
      small animal patients with ectopic ureters.

PMID- 10911682
TI  - Urethrotomy and urethrostomy in the dog.
AB  - An incision, or urethrotomy, is made into the urethral lumen to remove or relieve
      an obstruction temporarily. When permanent diversion of urine flow proximal to an
      obstructed, severely damaged, or diseased urethra is required, a urethrostomy is
      performed. Urethrostomy is also performed to diminish the risk of urethral
      obstruction due to recurrent urinary calculi that are not likely to be resolved
      with medical therapy. Whenever possible, to reduce the risk of urethral stricture
      or recurrent urinary tract infection, urethral surgery is avoided when an
      obstruction can be relieved by retrohydropropulsion or catheterization.
      Urethrotomy can be performed in the prescrotal or perineal regions depending on
      the level of the urethral obstruction. Although urethrostomy can be made in the
      perineal and antepubic positions, scrotal urethrostomy is the procedure of choice
      provided the lesion is distal to this area. Specific urethrotomy and urethrostomy
      procedures are described, including discussion about selection of the appropriate
      procedure for the urethral problem, patient stabilization considerations, general
      postoperative management, and risk of complications.

PMID- 10911683
TI  - Managing traumatic urethral injuries.
AB  - Urethral injuries are relatively common in male dogs and cats. Urethral
      epithelium has impressive regenerative properties, and healing by second
      intention is effective as long as there is mucosal continuity across the
      traumatized area. Principles of managing traumatic urethral injuries include an
      accurate patient assessment, including a determination of the extent of the
      urethral injury; correction of electrolyte or acid-base disturbances; provision
      of urinary diversion, particularly with pelvic or perineal urethral defects;
      drainage of extravasated urine; and selection of a surgical procedure to repair
      or bypass the injured portion of urethra. Treatment options include temporary
      urinary diversion through cystostomy or urethral catheterization and second
      intention healing, permanent bypassing of the traumatized area through
      urethrostomy proximal to the injury site, and primary repair of transection
      injuries. The scrotal site is the most frequently used and preferred site for
      urethrostomy in the male dog to bypass the injured penile urethra. Urethral
      surgery necessitates care and attentiveness to detail, considering that accurate
      approximation of urethral mucosa minimizes fibrosis and helps maintain an
      adequate luminal diameter. Avoidance of stricture and preservation of function
      are goals of managing traumatic urethral injuries.

PMID- 10911685
TI  - Prostatic surgery in the dog.
AB  - Prostatic diseases are commonly encountered in the dog and a significant
      proportion of these will require some form of surgical intervention for their
      successful resolution. The previous perception of the prostate as an obscure
      pelvic organ coupled with a range of heretofore complex and unsatisfactory
      surgical techniques have deterred many surgeons from attempting surgical
      intervention. The recent introduction of omentalization techniques for the
      management of prostatic infections and secretory abnormalities, which require
      only modest surgical expertise, has now provided simple solutions for all benign
      parenchymal diseases. However, neoplastic disease remains a difficult disease
      both to diagnose and manage.

PMID- 10911684
TI  - Renal transplantation in cats.
AB  - Feline renal transplantation can offer long-term survival with a normal quality
      of life for cats with renal failure. However, it is important to remember that
      renal transplantation is a treatment option and not a cure. Renal transplantation
      is never performed on an emergency basis or prophylactically. Feline renal
      transplantation requires special microvascular instruments and an operating
      microscope. Careful patient selection and perioperative monitoring have improved
      the success rate. The new microemulsified form of cyclosporine is recommended for
      immunosuppression. As survival times have steadily improved, long-term
      complications, such as diabetes and neoplasia, are now being recognized.

PMID- 10911686
TI  - Unintentional injuries in childhood: analysis and recommendations.

PMID- 10911687
TI  - The history of injury control and the epidemiology of child and adolescent
      injuries.
AB  - Unintentional injuries claim the lives of more children each year than any other
      cause of death. A substantial proportion of child hospitalizations and emergency
      department visits also are attributable to unintentional injuries. The
      conceptualization of unintentional injuries as a public health problem that is
      preventable has gained credibility over the past few decades, as effective
      solutions to reduce the burden of injuries--such as child safety seats, bicycle
      helmets, and smoke detectors--have been identified. Successful implementation of
      these strategies requires a clear understanding of the circumstances surrounding
      injuries and the risk and protective factors that influence the likelihood that a
      child will be injured. Although adequate data on these factors is available for
      some causes of injury, such as motor vehicle crashes, it is almost nonexistent
      for others, such as unintentional firearm injuries. Overall, unintentional injury
      rates are highest among adolescents ages 15 to 19, males, children from
      impoverished families, and minorities. Also, some injuries occur more often in
      rural areas. Although these demographic risk factors cannot be modified,
      environmental and behavioral risks, such as unsafe roads, alcohol intoxication,
      unfenced swimming pools, and the absence of a smoke detector in the home, can be
      modified successfully with appropriate strategies. Motor vehicle occupant,
      drowning, and pedestrian injuries were the most common unintentional injuries
      causing death among children ages 0 to 19 in 1996. Together, these mechanisms
      accounted for more than half of all unintentional injury deaths among children
      and adolescents, although rates varied considerably by age. Child injury death
      rates across most age categories and mechanisms of injury have declined during
      the past 20 years, yet the reasons for these declines are poorly understood.
      Additional research about risk and protective factors, and efforts to implement
      successful injury prevention strategies among populations at highest risk for
      injuries, are necessary to further reduce the toll on children's lives.

PMID- 10911688
TI  - Individual-level injury prevention strategies in the clinical setting.
AB  - Health care providers have numerous opportunities to intervene with parents and
      children to promote child safety practices that reduce rates of unintentional
      injuries. These individual-level interventions may be delivered in a variety of
      settings such as physician offices, clinics, emergency departments, or hospitals.
      This article systematically reviews 22 randomized controlled trials (RCTs) that
      examined the impact of interventions delivered in the clinical setting on child
      safety practices and unintentional injuries. The results indicate that counseling
      and other interventions in the clinical setting are effective at increasing the
      adoption of some safety practices, but not others. Specifically, motor vehicle
      restraint use, smoke alarm ownership, and maintenance of a safe hot tap water
      temperature were more likely to be adopted following interventions in the
      clinical setting. Clinical interventions were not proven effective at increasing
      a variety of safety practices designed to protect young children from injuries in
      the home, increasing bicycle helmet use, or reducing the occurrence of childhood
      injuries, though few studies examined the latter two outcomes. Clinical
      interventions were most effective when they combined an array of health education
      and behavior change strategies such as counseling, demonstrations, the provision
      of subsidized safety devices, and reinforcement. The article concludes with
      implications for research and practice.

PMID- 10911689
TI  - Community-based injury prevention interventions.
AB  - Community-based interventions offer a promising solution for reducing child and
      adolescent unintentional injuries. By focusing on altering behavior, promoting
      environmental change within the community, or passing and enforcing legislation,
      these interventions seek to change social norms about acceptable safety
      behaviors. This article systematically reviews 32 studies that evaluated the
      impact of community-based injury prevention efforts on childhood injuries, safety
      behaviors, and the adoption of safety devices. Interventions targeted schools,
      municipalities, and cities. Most relied on an educational approach, sometimes in
      combination with legislation or subsidies, to reduce the cost of safety devices
      such as bicycle helmets. Results indicate that community-based approaches are
      effective at increasing some safety practices, such as bicycle helmet use and car
      seat use among children. The evidence is less compelling that such interventions
      increase child pedestrian safety, increase adolescent vehicle safety by reducing
      drinking and driving behaviors, or reduce rates of several categories of
      childhood injuries. Strong evidence supporting the effectiveness of community
      based interventions is lacking, in part because few studies used randomized
      controlled designs or examined injury rates among children and youths as outcome
      measures. Nonetheless, this review identifies common elements of successful
      community-based approaches that should be replicated in future studies. First,
      the use of multiple strategies grounded in a theory of behavior change is
      critical. Second, to maximize success, interventions should be integrated into
      the community and approaches should be tailored to meet unique community needs.
      Third, community stakeholders should be included in the development of community
      based strategies. This community involvement and ownership of the intervention
      increases the likelihood of modeling and peer pressure, leading to widespread
      adoption of a safety behavior. Finally, when possible, a randomized controlled
      design should be used to maximize the trustworthiness of reported findings and
      aid decisions about where to invest resources in community-based approaches to
      injury prevention.

PMID- 10911690
TI  - Legislative and regulatory strategies to reduce childhood unintentional injuries.
AB  - Laws and regulations are among the most effective mechanisms for getting large
      segments of the population to adopt safety behaviors. These have been applied at
      both the state and federal levels for diverse injury issues. Certain legal
      actions are taken to prevent the occurrence of an otherwise injury-producing
      event, while other legal actions are designed to prevent injury once an event has
      occurred. At the federal level, effective laws and regulations have been directed
      at dangers posed by unsafe manufactured products or motor vehicle design. At the
      state level, effective safety laws and regulations have been directed at
      encouraging safety behaviors and regulating the use of motor vehicles or other
      forms of transportation. In this article, six legislative efforts are described
      to point out pros and cons of the legislative approach to promoting safety. Three
      such efforts are aimed at preventing injury-producing events from occurring:
      mandating child-resistant packaging for prescription drugs and other hazardous
      substances, regulating tap water temperature by presetting a safe hot-water
      heater temperature at the factory, and graduated licensing. Three other examples
      illustrate the value and complexities of laws designed to prevent injuries once
      an injury-producing event does occur: mandatory bicycle helmet use, sleep-wear
      standards, and child safety seat use. This article concludes with specific
      recommendations, which include assessing the value of laws and regulations,
      preventing the rescission of laws and regulations known to work, refining
      existing laws to eliminate gaps in coverage, developing regulations to adapt to
      changing technology, exploring new legal means to encourage safe behavior, and
      increasing funding for basic and applied research and community programs. Further
      reductions in childhood injury rates will require that leaders working in the
      field of injury prevention together provide the creativity to devise new safety
      devices and programs, incentives to persuade the public to adopt a "culture of
      safety" as a social norm, training and education to develop new leaders and
      workers, and the political will to challenge the status quo and engage the public
      interest.

PMID- 10911691
TI  - The cost of childhood unintentional injuries and the value of prevention.
AB  - Cost data are useful in comparing various health problems, assessing risks,
      setting research priorities, and selecting interventions that most efficiently
      reduce health burdens. Using analyses of national and state data sets, this
      article presents data on the frequency, costs, and quality-of-life losses
      associated with unintentional childhood injuries in 1996. The frequency,
      severity, potential for death and disability, and costs of unintentional injury
      make it a leading childhood health problem. Unintentional childhood injuries in
      1996 resulted in an estimated $14 billion in lifetime medical spending, $1
      billion in other resource costs, and $66 billion in present and future work
      losses. These injuries imposed quality-of-life losses equivalent to 92,400 child
      deaths. Since Medicaid and other government sources paid for 39% of the days
      children spent in hospitals due to unintentional injuries, the government has a
      financial interest in, and arguably a responsibility for, assuring the safety of
      disadvantaged children. Federal agencies, however, devote relatively few public
      dollars to injury prevention research and programming. Several proven child
      safety interventions cost less than the medical and other resource costs they
      save. Thus, governments, managed care companies, and third-party payers could
      save money by encouraging the routine use of selected child safety measures such
      as child safety seats, bicycle helmets, and smoke detectors. Yet, these and other
      proven injury prevention interventions are not universally implemented.

PMID- 10911692
TI  - Evaluating injury prevention programs: the Oklahoma City Smoke Alarm Project.
AB  - Evaluation of injury prevention programs is critical for measuring program
      effects on reducing injury-related morbidity and mortality or on increasing the
      adoption of safety practices. During the planning and implementation of injury
      prevention programs, evaluation data also can be used to test program strategies
      and to measure the program's penetration among the target population. The
      availability of this early data enables program managers to refine a program,
      increasing the likelihood of successful outcomes. The Oklahoma City Smoke Alarm
      Project illustrates how an evaluation was designed to inform program decisions by
      providing methodologically sound data on program processes and outcomes. This
      community intervention trial was instituted to reduce residential fire-related
      injuries and deaths in a geographic area of Oklahoma City that was
      disproportionately affected by this problem. The distribution of free smoke
      alarms in targeted neighborhoods was accompanied by written educational pamphlets
      and home-based follow-up to test whether the alarms were functioning correctly.
      Early evaluation during the planning and implementation phases of the program
      allowed for midcourse corrections that increased the program's impact on desired
      outcomes. During the six years following the project, the residential fire
      related injury rate decreased 81% in the target population but only 7% in the
      rest of Oklahoma City. This dramatic decline in fire-related injuries in the
      target area is largely attributed to the free smoke alarm distribution as well as
      to educational efforts promoting awareness about residential fires and their
      prevention.

PMID- 10911693
TI  - Training injury control practitioners: the Indian Health Service model.
AB  - Many individuals practicing injury control have not received specific training
      for their work, in large part because of a scarcity of training opportunities.
      Consistent with its mission of "raising the health status of American Indian and
      Alaska Native people to the highest possible level," the Indian Health Service
      (IHS) created an innovative training program for federal and tribal employees.
      The model emphasizes training that is practical and can be applied immediately to
      community interventions. Many features of the IHS training model have broad
      applicability to other settings. These features include the use of experiential
      instruction, preceptors, and community case studies to train individuals from
      diverse cultural and educational backgrounds; educational strategies for employed
      adults; and courses that promote community empowerment. The development of IHS
      training courses are guided by community input, epidemiological data, advances in
      knowledge, and program evaluations. Courses range from a half-day "minicourse" to
      a full-year fellowship program. The success of the training model is evident in
      programs instituted by IHS Injury Prevention Specialist Fellowship graduates,
      whose projects have ranged from drowning prevention in Alaska to fire safety in
      North Dakota. The IHS training model could be applied in a variety of other
      community-based settings, but it is most relevant to programs that train
      individuals from diverse backgrounds who are not full-time students and programs
      that make community needs an organizational priority.

PMID- 10911694
TI  - Prometheus and the litigators. A mediation odyssey.

PMID- 10911695
TI  - "Where the public peril begins". 25 years after Tarasoff.

PMID- 10911696
TI  - The online message board controversy. Physicians hit with claims of libel and
      insider trading by their employers.

PMID- 10911697
TI  - Informed consent issues throughout the birthing process.

PMID- 10911698
TI  - [The document on children's health is a good start, but more must be involved].

PMID- 10911699
TI  - [Significance of child health services for children's health. Possibilities and
      limitations in a future perspective].

PMID- 10911700
TI  - [Research on bonding. The significance of early attachment between parents and
      children is confirmed].

PMID- 10911701
TI  - [Is it possible to become a "better" parent? Inadequate early attachment between
      parents and children seems to be preventable/treatable].

PMID- 10911702
TI  - [Historical glimpses on child health care and pediatric research. Swedish
      pediatrics in a world-leading position at the start of the 20th century].

PMID- 10911703
TI  - [Cardiovascular side-effects of triptanes in migraine exist but are rare. 5-HT
      receptor mediated extracranial vasoconstriction is the most common cause].
AB  - Triptans, 5-HT1B/1D agonists used in migraine treatment, are rarely involved in
      serious coronary events due to vasospasm. 5 HT1 receptors mediate vasodilation
      and vasoconstriction of coronary arteries. Reports of serious coronary events
      mainly concern patients with known risk factors for coronary artery disease. It
      is prudent to obtain a thorough medical history before treatment with a triptan
      is started. If chest pain occurs, the possibility of coronary ischemia should be
      investigated. Stroke, a known complication to migraine, has also been reported in
      patients treated with triptans, but available data do not suggest that triptans,
      when correctly used, greatly increase the risk.

PMID- 10911704
TI  - ["And how will it be in the future...?" Patients' needs of meaning can be met--or
      obstructed].

PMID- 10911705
TI  - [A moment in medicine, part 10. Language, a tool and a fire].

PMID- 10911707
TI  - [Inadequate bonding is a risk factor].

PMID- 10911706
TI  - [Views on a document from the MFR: Evidence-based child health care or...?].

PMID- 10911708
TI  - [Where is the competence to go if the contact with physicians will be thinned
      out?].

PMID- 10911709
TI  - The Swedish mammography screening trials. Check up on your sources.

PMID- 10911710
TI  - Final comment. The articles by Gotzsche and Olsen are not official Cochrane
      reviews and lack scientific merit.

PMID- 10911711
TI  - [Medical technology--a godsent gift or a complement to a dialogue-based
      medicine?].

PMID- 10911712
TI  - [The discussion on the utilization of working time is justified].

PMID- 10911713
TI  - [Dialogue between theologians and scientists--yes, but is there an interest?].

PMID- 10911714
TI  - [PET in Lund--some information].

PMID- 10911715
TI  - Oncological problems in pancreatic cancer surgery.
AB  - Despite the development of more sophisticated diagnostic techniques, it remains
      difficult to detect pancreatic carcinoma in the early stage. The resection rate
      has been increasing due to recent advances in surgical techniques and the
      application of extensive surgery. However, the postoperative prognosis has been
      poor due to commonly occurring liver metastasis. Recent molecular-biological
      studies have been clarifying occult liver metastasis and systemic disease in
      pancreatic cancer. This paper will review our experience and several problems in
      pancreatic cancer surgery.

PMID- 10911716
TI  - Cell biology of caveolae and its implication for clinical medicine.
AB  - Caveolae are small invaginations of the plasma membrane found in many cell types,
      and caveolins are integral membrane proteins that form the framework of caveolae.
      In the past several years, research on caveolae has developed explosively, and
      caveolae and/or caveolins have been shown to play many important roles in cell
      physiology: in particular, they are thought to be related to signal transduction,
      cholesterol transport, endocytosis and tumor suppression. On the other hand, some
      studies have suggested that another membrane domain called rafts is also involved
      in the same processes, and some confusion remains concerning the relationship
      between these two domains. Abnormalities in caveolae and/or caveolins have been
      found in various diseases, including cancer, atherosclerosis, muscular dystrophy
      and the Alzheimer's disease, which may make this domain a new focus for
      pharmacological research. This review will focus on the cell biology of caveolae,
      caveolins and rafts, and then summarize the implications of these findings for
      clinical studies.

PMID- 10911717
TI  - Evaluation of the Space Collaboration System: its history, image quality and
      effectiveness for joint case conference.
AB  - A joint case-conference was conducted between the Departments of Radiology at
      Nagoya and Kobe Universities using the Space Collaboration System (SCS), which
      connects 39 national universities and institutes by communication satellite. In
      the conference, both sides presented cases using medical images such as those
      from CT, MRI, and DSA, and the cases were discussed between participants at the
      two universities. After the final conference, we distributed a questionnaire to
      solicit responses from the 43 participating radiologists on the quality of the
      transferred images and their overall impression of the conference. The responses
      showed that the CT, MRI, and DSA images were clear enough to allow discussion,
      whereas the plain X-ray images were not. Hence from the standpoint of image
      quality, the SCS may be unsuited for medical image diagnosis, but useful for
      presentation of case images in joint conferences and seminars.

PMID- 10911719
TI  - Water fat separation using the single acquisition "sandwich" type 3-point Dixon
      method to optimize knee joint scans.
AB  - In this paper, we tried to evaluate the effect of water-fat separation on and to
      optimize the scan condition of the newly developed "Sandwiched" 3-point Dixon
      method at 0.35 Tesla (T), for knee joint imaging. Using a 0.35T superconductive
      open magnet system with a solenoid type knee coil, one male and two female normal
      volunteers (27-37 y.o.) underwent knee joint imaging. Each sequence provided good
      water-fat separated images. At 0.35T, the gradient echo provided a better
      contrast than the spin echo. Optimal cartilage-marrow and cartilage-fluid
      contrast could be obtained at a frip angle (FA) of 90 degrees. There was no
      significant correlation between cartilage-marrow, cartilage-fluid contrast and
      repetition time (TR) values within the tested range. Cartilage-fluid and
      cartilage-marrow contrast were both best at an FA of 90 degrees with the gradient
      echo sequence. TR from 350 ms to 650 ms did not cause any significant contrast
      difference in the fat suppressed images. This method is useful and could be the
      only practical choice for obtaining fat suppressed T1 weighted images for joint
      magnetic resonance (MR) imaging at 0.35T.

PMID- 10911718
TI  - Identification of plasma antibody epitopes and gene abnormalities in Japanese
      hemophilia A patients with factor VIII inhibitor.
AB  - Eleven Japanese hemophilia A patients with anti-factor VIII (FVIII) inhibitors
      were studied to localize both their inhibitory antibody epitopes and their
      genotypes. The inhibitor epitopes were studied in nine severe hemophilia A
      patients by means of a scanning method using the oligopeptide panel covering the
      FVIII polypeptides without the B domain. The 107 15 mer-peptides were synthesized
      on solid-phase pins and analyzed for their reactivity with diluted patient
      plasma. As indicated previously, a series of peptides corresponding to the A2 and
      C2 domains were recognized by plasma antibodies from 2 patients and 4 patients,
      respectively. In contrast, all the antibodies bound to several epitopes in the A3
      domain, while an epitope 1809-1821 covering the putative factor IX binding site
      was found in 3 patients. Southern blotting analysis showed that 8 out of 11
      patients had either gene deletions or inversions of the FVIII gene, indicating a
      higher proportion of gross gene alterations in inhibitor-positive hemophilia A
      patients. However, the correlation of gene abnormality type with epitope location
      was not fully established.

PMID- 10911720
TI  - A preliminary analysis of platelet von Willebrand factor oligosaccharides.
AB  - Little is known about the carbohydrate structure of the platelet von Willebrand
      factor (vWf). We have analyzed N-linked oligosaccharides from both plasma and
      platelet vWf by Fluorophore-Assisted-Carbohydrate Electrophoresis (FACE) and
      isoelectric focusing before and after digestion of the proteins with
      neuraminidase. We observed a greater variety of N-linked oligosaccharides derived
      from plasma vWf than from platelet vWf. Neuraminidase treatment reduced the
      oligosaccharides from both proteins to only two or three bands and produced
      significant increases in their isoelectric points.

PMID- 10911721
TI  - A discussion of anti-Aspergillus niger glucose oxidase monoclonal antibody
      reactivity to red blood cells of several species.
AB  - We observed that mouse spleen cells from rosettes with autologous red blood cells
      (RBCs) and that rosette-formation was suppressed by anti-Aspergillus niger
      glucose oxidase monoclonal antibody (mAb). In the present study, we investigated
      whether RBCs of species besides mice have the structure recognized by anti-A.
      niger glucose oxidase mAb by using rosette-formation and complement-mediated
      hemolysis. Lysates of monkey and human RBCs did not suppress rosette-formation
      whereas autologous (mouse), rat and sheep RBC lysates partially suppressed
      rosette-formation. Those lysates exerted their suppressive activity after they
      had been treated at 56 degrees C for 30 min. A. niger glucose oxidase also
      suppressed rosette-formation with or without treatment at 56 degrees C for 30
      min. Alternatively, anti-A. niger glucose oxidase mAb lysed mouse, rat and sheep
      RBCs but not human RBCs with complement. These findings suggest that the cell
      surfaces of mouse, rat and sheep RBCs have a structure which can be recognized by
      anti-A. niger glucose oxidase mAb while the cell surfaces of monkey and human
      RBCs do not.

PMID- 10911723
TI  - The photophysical properties of menthyl anthranilate: a UV-A sunscreen.
AB  - The results of a comprehensive investigation of the photophysical properties of
      the sunscreen agent menthyl anthranilate in various solvent systems are reported.
      Luminescence studies reveal that this ester is highly fluorescent (phi f = 0.64
      +/- 0.06 in ethanol) and has a solvent-dependent emission maximum in the range of
      390-405 nm. Phosphorescence has also been detected in low-temperature glasses
      with an emission maximum at 445 nm and a lifetime of 2.5 s. Kinetic UV-visible
      absorption measurements revealed a transient species with absorption maxima at
      480 nm and solvent-dependent lifetimes of 26-200 microseconds that are attributed
      to the triplet state. The triplet state is efficiently quenched by oxygen,
      leading to the formation of singlet oxygen in all of the solvent systems studied.
      The singlet-oxygen quantum yields (phi delta) determined by time-resolved near
      infrared luminescence measurements were determined to be in the range 0.09-0.12
      for all systems.

PMID- 10911722
TI  - Photo-oxidation of methionine-containing peptides by the 4-carboxybenzophenone
      triplet state in aqueous solution. Competition between intramolecular two
      centered three-electron bonded (S...S)+ and (S...N)+ formation.
AB  - Quantum yields for the formation of transients were measured following the
      quenching of triplet 4-carboxy-benzophenone (3CB*) by methionine-containing
      peptides in aqueous solutions. Ketyl radicals (CBH.), ketyl radical anions (CB.-)
      and various sulfur radical cations were identified following the triplet
      quenching events. The presence of these intermediates indicated that the triplet
      quenching mechanism can be characterized as mainly electron-transfer in nature.
      The quenching rate constants were of the order of 2 x 10(9) M-1 s-1. There were
      small, but significant, differences in the triplet-quenching rate constants, and
      these trends indicate the existence of multiple sulfur targets in the quenchers.
      The absorption of the transient products was followed in detail by using spectral
      resolution analysis. From the absorption data, quantum yields were estimated for
      the formation of the various transients. There were differences found in the
      yields of the transient products between the experiments, where the quenchers
      were the "mixed" stereoisomers of methionylmethionine (L,D and D,L) and
      experiments where the quenchers were L,L and D,D stereoisomers. Triplet-quenching
      data from several other methionine-containing small oligopeptides were analyzed
      in an analogous manner. Systematic variations were observed, and these patterns
      were discussed in terms of competitive donation of protons to the CB.- within the
      charge-transfer complex. The competition was between protons on carbons adjacent
      to the sulfur-radical center and protons on the protonated amino groups of the
      radical cation. In addition, there was a competition between the two
      intramolecular two-centered, three-electron bonded species (S therefore S)+ and
      (S therefore N)+ that play roles in the secondary kinetics.

PMID- 10911724
TI  - Protein changes in HL60 leukemia cells associated with 5-aminolevulinic acid
      based photodynamic therapy. Early effects on endoplasmic reticulum chaperones.
AB  - Using two-dimensional electrophoresis we investigated the effect of 5
      aminolevulinic acid (ALA)-based photodynamic therapy (PDT; induction with 1 mM
      ALA for 4 h followed by blue light dose of 18 J/cm2) on the protein expression in
      HL60 leukemia cells. ALA-PDT resulted in extensive qualitative and quantitative
      changes in the protein pattern of HL60 cell lysates. Of more than 1350 protein
      spots recognized on the protein maps of ALA-induced cells, seven proteins were
      enhanced and 17 suppressed following irradiation. Three of these, calreticulin
      precursor, p58 microsomal protein (ERp57) and protein disulfide isomerase (p55)
      have been identified by matrix-assisted laser desorption and ionization-mass
      spectrometry and the pI/molecular weight parameters of the affected proteins were
      estimated by computer analysis. The findings suggest participation of endoplasmic
      reticulum Ca(2+)-binding chaperones and/or Ca2+ signaling in ALA-PDT mediated
      cytotoxicity.

PMID- 10911725
TI  - Photoaddition of 4,6-dimethyltetrahydrobenzoangelicin to thymine in DNA: X-ray
      studies and experiments with model oligonucleotides.
AB  - The crystal structures of 4,6-dimethyltetrahydrobenzoangelicin (THBA), a
      furocoumarin analog, and of its furan-side cis-syn cycloadduct with thymine
      formed in the photoreaction with DNA, have been determined. The crystal structure
      of the latter compound contained only one enantiomeric form corresponding to the
      addition to a 5'-XpT site. Contrary to most psoralen derivatives studied, THBA
      showed higher photoreactivity toward synthetic oligonucleotides containing that
      sequence than toward those with the 5'-TpX sequence.

PMID- 10911726
TI  - A ruthenium probe for cell viability measurement using flow cytometry, confocal
      microscopy and time-resolved luminescence.
AB  - The capability of the new luminescent probe (dibenzo[h,j] dipyrido[3,2-a:2',3'
      c]phenazine)bis(2,2'-bipyridine)ruthenium(II) dication, (RB2Z), to discriminate
      live and dead cells has been tested on rat hepatocytes and mouse lymphocytes.
      RB2Z-stained cells were analyzed using flow cytometry, fluorescence (confocal)
      microscopy and time-resolved luminescence measurements. The established viability
      probes propidium iodide (PI) and SYTOX green (SG) were used as controls. The
      intense luminescence of RB2Z at 606 nm is localized in the nucleus of nonviable
      cells. Viability measurements by flow cytometry and fluorescence microscopy using
      RB2Z as dead-cell marker yield the same results as PI and SG. The luminescence
      lifetime of RB2Z also displays sensitivity to cell viability (0.45 and 0.82
      microsecond in presence of fully viable and dead cells, respectively). This
      ruthenium complex is photostable under laser sources and its 200 nm Stokes shift
      facilitates multicolor labeling experiments in flow cytometry and fluorescence
      microscopy. Unlike the currently available probes, the long-lived excited state
      of RB2Z also allows assays based on luminescence decay measurements.

PMID- 10911727
TI  - Conformational changes induced in the Tet repressor protein TetR(B) upon operator
      or anhydrotetracycline binding as revealed by time-resolved fluorescence
      spectroscopy on single tryptophan mutants.
AB  - We have analyzed the tryptophan (trp) fluorescence-decay kinetics of single trp
      mutants of the Tet repressor protein in the free, the tet operator and
      anhydrotetracycline (atc)-bound states. The position of the single trp varies
      between residues 164 and 171, in close proximity to one entrance of the
      tetracycline-binding pocket. A good fit of the trp fluorescence decay needed
      generally three exponentials. The decay times vary with detection wavelength, the
      extent of this variation being correlated to the variation of the emission
      maximum. Quenching experiments with neutral (acrylamide), cationic (N
      methylpyridinium chloride) and anionic quencher (KI) support the interpretation
      of the three fluorescence components within a conformer model. Operator and atc
      binding change the ratio of the relative amplitudes of the medium- and long-lived
      component, thus pointing to structural changes as indicated also by the changes
      in decay time. Since the fluorescence decay is different between the free, atc-
      and operator-bound states we conclude that the protein structure is different in
      each of these three states. The fluorescence quenching constants reflect not only
      the variation in solvent exposure with position, but also the fact that the net
      surface charge in this region is negative, because the quenching constants by the
      cationic quencher are up to 10-fold higher. The atc fluorescence appears to decay
      monoexponentially with about the same decay time for all mutants, except W170, in
      which the trp residue sterically interferes with atc.

PMID- 10911728
TI  - Meso-substituted cationic porphyrins of biological interest. Photophysical and
      physicochemical properties in solution and bound to liposomes.
AB  - A series of cationic porphyrins with 1-4 positive charges are studied: mono(N
      methyl-4-pyridyl)triphenylporphine chloride [Mono], cis(N-methyl-4
      pyridyl)diphenylporphine chloride [Cis], tri(N-methyl-4
      pyridyl)monophenylporphine chloride [Tri] and tetra(N-methyl-4-pyridyl)porphine
      chloride [Tetra]. Their photophysical properties are measured in small
      unilamellar vesicles and compared with those in homogeneous solution. Liposomes
      of L-alpha-dimyristoyl-phosphatidylcholine (100 nm diameter) and L-alpha
      dipalmitoyl-phosphatidylcholine (50 nm diameter) in phosphate-buffered saline (pH
      = 7.4) or D2O 0.15 M NaCl were used. The effect of the medium microheterogeinity
      is discussed. The triplet quantum yields in liposomes for all the porphyrins are
      about 0.7, similar to the value obtained for Tetra in aqueous media. The singlet
      molecular oxygen quantum yields for the hydrophilic compounds Tri and Tetra are
      greater than those of the hydrophobic ones, Mono and Cis. Also, association
      constants (KL) of the dyes to liposomes and their localization within the
      membranes are determined from fluorescence and fluorescence polarization
      measurements, respectively. KL values are in the range of 10(4)-10(5) M-1 for all
      the compounds, indicating that hydrophobic and coulombic interactions between
      porphyrins and liposomes are responsible for the dye association. Fluorescence
      polarization experiments indicate that Mono and Cis can penetrate into the
      lipidic phase, and that Tri and Tetra are located near the polar heads of the
      lipidic molecules.

PMID- 10911729
TI  - Active uptake of drugs into photosensitive liposomes and rapid release on UV
      photolysis.
AB  - Liposomes containing high concentrations of the anticancer drug doxorubicin,
      prepared by active-loading techniques, have been intensively investigated as
      potential agents for chemotherapy. The present study investigates the possibility
      of active uptake and photoinduced release of such solutes from liposomes
      incorporating a photoisomerizable lipid. The active loading of acridine orange
      and doxorubicin was investigated using liposomes containing entrapped ammonium
      sulfate. The liposomes were prepared with dipalmitoyl-L-alpha-phosphatidyl
      choline (DPPC) and a photochromic lipid, (1,2-(4'-n-butylphenyl)azo-4'-(gamma
      phenylbutyroyl))-glycero-3- phosphocholine (Bis-Azo PC), which isomerizes on
      exposure to near-UV light with resulting changes in membrane permeability to
      solutes. The rate of loading of the vesicles below the phase transition
      temperature of DPPC was investigated as a function of Bis-Azo PC and cholesterol
      concentrations in the liposome. The rate of doxorubicin uptake was found to be
      greatly decreased in the presence of cholesterol, while below 30 degrees C the
      rate of acridine orange uptake was increased in the presence of cholesterol. On
      exposure to a single UV laser pulse, actively loaded acridine orange was rapidly
      released from liposomes containing Bis-Azo PC at a rate similar to that found for
      the indicator dye calcein. However while cholesterol had previously been shown to
      greatly enhance the rate of photo-induced calcein leakage, it had no significant
      effect on the rate of acridine orange release. After active loading into DPPC
      vesicles containing Bis-Azo PC, doxorubicin was also released after exposure to a
      single laser pulse, but at a rate slower than for acridine orange and calcein.
      The difference in behavior between these systems is ascribed to the interactions
      of acridine orange and doxorubicin with the liposome bilayer. Photoinduced
      release of pharmacologically active materials from sensitized liposomes might
      provide a useful adjunct or alternative to conventional photodynamic therapy.

PMID- 10911730
TI  - Damage to DNA in bacterioplankton: a model of damage by ultraviolet radiation and
      its repair as influenced by vertical mixing.
AB  - A model of UV-induced DNA damage in oceanic bacterioplankton was developed and
      tested against previously published and novel measurements of cyclobutane
      pyrimidine dimers (CPD) in surface layers of the ocean. The model describes the
      effects of solar irradiance, wind-forced mixing of bacterioplankton and optical
      properties of the water on net DNA damage in the water column. The biological
      part includes the induction of CPD by UV radiation and repair of this damage
      through photoreactivation and excision. The modeled damage is compared with
      measured variability of CPD in the ocean: diel variation in natural
      bacterioplankton communities at the surface and in vertical profiles under
      different wind conditions (net damage as influenced by repair and mixing); in
      situ incubation of natural assemblages of bacterioplankton (damage and repair, no
      mixing); and in situ incubation of DNA solutions (no repair, no mixing). The
      model predictions are generally consistent with the measurements, showing similar
      patterns with depth, time and wind speed. A sensitivity analysis assesses the
      effect on net DNA damage of varying ozone thickness, colored dissolved organic
      matter concentration, chlorophyll concentration, wind speed and mixed layer
      depth. Ozone thickness and mixed layer depth are the most important factors
      affecting net DNA damage in the mixed layer. From the model, the total
      amplification factor (TAF; a relative measure of the increase of damage
      associated with a decrease in ozone thickness) for net DNA damage in the euphotic
      zone is 1.7, as compared with 2.1-2.2 for irradiance weighted for damage to DNA
      at the surface.

PMID- 10911731
TI  - The effect of decreasing temperature up to chilling values on the in vivo
      F685/F735 chlorophyll fluorescence ratio in Phaseolus vulgaris and Pisum sativum:
      the role of the photosystem I contribution to the 735 nm fluorescence band.
AB  - The effect of leaf temperature (T), between 23 and 4 degrees C, on the
      chlorophyll (Chl) fluorescence spectral shape was investigated under moderate
      (200 microE m-2 s-1) and low (30-35 microE m-2 s-1) light intensities in
      Phaseolus vulgaris and Pisum sativum. With decreasing temperature, an increase in
      the fluorescence yield at both 685 and 735 nm was observed. A marked change
      occurred at the longer emission band resulting in a decrease in the Chl
      fluorescence ratio, F685/F735, with reducing T. Our fluorescence analysis
      suggests that this effect is due to a temperature-induced state 1-state 2
      transition that decreases and increases photosystem II (PSII) and photosystem I
      (PSI) fluorescence, respectively. Time-resolved fluorescence life-time
      measurements support this interpretation. At a critical temperature (about 6
      degrees C) and low light intensity a sudden decrease in fluorescence intensity
      was observed, with a larger effect at 685 than at 735 nm. This is probably linked
      to a modification of the thylakoid membranes, induced by chilling temperatures,
      which can alter the spill-over from PSII to PSI. The contribution of photosystem
      I to the long-wavelength Chl fluorescence band (735 nm) at room temperature was
      estimated by both time-resolved fluorescence lifetime and fluorescence yield
      measurements at 685 and 735 nm. We found that PSI contributes to the 735 nm
      fluorescence for about 40, 10 and 35% at the minimal (F0), maximal (Fm) and
      steady-state (Fs) levels, respectively. Therefore, PSI must be taken into account
      in the analysis of Chl fluorescence parameters that include the 735 nm band and
      to interpret the changes in the Chl fluorescence ratio that can be induced by
      different agents.

PMID- 10911732
TI  - Spectroscopic properties of protochlorophyllide analyzed in situ in the course of
      etiolation and in illuminated leaves.
AB  - The spectroscopic properties of photoactive (i.e. flash-transformable) and
      nonphotoactive protochlorophyll(ide)s (Pchl(ide)) were reinvestigated during the
      development of bean leaves in darkness. Two phases in the process of Pchl(ide)
      accumulation were apparent from quantitative measurements of pigment content: a
      lag phase (first week) during which photoactive Pchl(ide) accumulated faster than
      nonphotoactive Pchl(ide); and a fast phase (second week), showing parallel
      accumulation of both types of Pchl(ide). 'Flashed-minus-dark' absorbance
      difference spectra recorded in situ at 77 K showed that P650-655 was the
      predominant form of photoactive protochlorophyllide regardless of developmental
      stage. Quantitative analysis of energy migration processes between the Pchl(ide)
      forms showed the existence of energy transfer units containing a 1:8 ratio of
      nonphotoactive and photoactive Pchl(ide)s during development. Gaussian
      deconvolution of in situ 77 K fluorescence spectra indicated that the 633 nm band
      of nonphotoactive Pchl(ide) was made of four bands, at 625, 631, 637 and 643 nm,
      whose relative amplitudes only slightly changed during development. The emission
      band of photoactive Pchlide was also analyzed using the same method. Three
      components were found at 644, 652 and 657 nm. The emission band of P650-655
      included the last two components, which become predominant only in fully
      etiolated plants. Photoactive Pchlide with an emission maximum at 653 nm was
      detected in the light during development of leaves of photoperiodically grown
      plants.

PMID- 10911733
TI  - Pharmacokinetics of ICG and HPPH-car for the detection of normal and tumor tissue
      using fluorescence, near-infrared reflectance imaging: a case study.
AB  - We present in vivo fluorescent, near-infrared (NIR), reflectance images of
      indocyanine green (ICG) and carotene-conjugated 2-devinyl-2-(1-hexyloxyethyl)
      pyropheophorbide (HPPH-car) to discriminate spontaneous canine adenocarcinoma
      from normal mammary tissue. Following intravenous administration of 1.0 mg kg-1
      ICG or 0.3 mg kg-1 HPPH-car into the canine, a 25 mW, 778 nm or 70 mW, 660 nm
      laser diode beam, expanded by a diverging lens to approximately 4 cm in diameter,
      illuminated the surface of the mammary tissue. Successfully propagating to the
      tissue surface, ICG or HPPH-car fluorescence generated from within the tissue was
      collected by an image-intensified, charge-coupled device camera fitted with an
      830 or 710 nm bandpass interference filter. Upon collecting time-dependent
      fluorescence images at the tissue surface overlying both normal and diseased
      tissue volumes, and fitting these images to a pharmacokinetic model describing
      the uptake (wash-in) and release (wash-out) of fluorescent dye, the
      pharmacokinetics of fluorescent dye was spatially determined. Mapping the
      fluorescence intensity owing to ICG indicates that the dye acts as a blood pool
      or blood persistent agent, for the model parameters show no difference in the ICG
      uptake rates between normal and diseased tissue regions. The wash-out of ICG was
      delayed for up to 72 h after intravenous injection in tissue volumes associated
      with disease, because ICG fluorescence was still detected in the diseased tissue
      72 h after injection. In contrast, HPPH-car pharmacokinetics illustrated active
      uptake into diseased tissues, perhaps owing to the overexpression of LDL
      receptors associated with the malignant cells. HPPH-car fluorescence was not
      discernable after 24 h. This work illustrates the ability to monitor the
      pharmacokinetic delivery of NIR fluorescent dyes within tissue volumes as great
      as 0.5-1 cm from the tissue surface in order to differentiate normal from
      diseased tissue volumes on the basis of parameters obtained from the
      pharmacokinetic models.

PMID- 10911734
TI  - Optimal excitation wavelengths for in vivo detection of oral neoplasia using
      fluorescence spectroscopy.
AB  - There is no satisfactory mechanism to detect premalignant lesions in the upper
      aero-digestive tract. Fluorescence spectroscopy has potential to bridge the gap
      between clinical examination and invasive biopsy; however, optimal excitation
      wavelengths have not yet been determined. The goals of this study were to
      determine optimal excitation-emission wavelength combinations to discriminate
      normal and precancerous/cancerous tissue, and estimate the performance of
      algorithms based on fluorescence. Fluorescence excitation-emission matrices (EEM)
      were measured in vivo from 62 sites in nine normal volunteers and 11 patients
      with a known or suspected premalignant or malignant oral cavity lesion. Using
      these data as a training set, algorithms were developed based on combinations of
      emission spectra at various excitation wavelengths to determine which excitation
      wavelengths contained the most diagnostic information. A second validation set of
      fluorescence EEM was measured in vivo from 281 sites in 56 normal volunteers and
      three patients with a known or suspected premalignant or malignant oral cavity
      lesion. Algorithms developed in the training set were applied without change to
      data from the validation set to obtain an unbiased estimate of algorithm
      performance. Optimal excitation wavelengths for detection of oral neoplasia were
      350, 380 and 400 nm. Using only a single emission wavelength of 472 nm, and 350
      and 400 nm excitation, algorithm performance in the training set was 90%
      sensitivity and 88% specificity and in the validation set was 100% sensitivity,
      98% specificity. These results suggest that fluorescence spectroscopy can provide
      a simple, objective tool to improve in vivo identification of oral cavity
      neoplasia.

PMID- 10911735
TI  - Subcellular localization of merocyanine 540 (MC540) and induction of apoptosis in
      murine myeloid leukemia cells.
AB  - Subcellular localization of photosensitizers is thought to play a critical role
      in determining the mode of cell death after photodynamic treatment (PDT) of
      leukemia cells. Using confocal laser scanning microscopy and fluorescent
      organelle probes, we examined the subcellular localization of merocyanine 540
      (MC540) in the murine myeloid leukemia M1 and WEHI 3B (JCS) cells. Two patterns
      of localization were observed: in JCS cells, MC540 was found to localize on the
      plasma membrane and mitochondria; and in M1 leukemia cells, MC540 was found to
      localize on lysosomes. The relationship between subcellular localization of MC540
      and PDT-induced apoptosis was investigated. Apoptotic cell death, as judged by
      the formation of apoptotic nuclei, was observed 4 h after irradiation in both
      leukemia cell lines. Typical ladders of apoptotic DNA fragments were also
      detected by DNA gel electrophoresis in PDT-treated JCS and M1 cells. At the
      irradiation dose of 46 kJ/m2 (LD90 for JCS and LD86 for M1 cells), the percentage
      of apoptotic JCS and M1 cells was 78 and 38%, respectively. This study provided
      substantial evidence that MC540 localized differentially in the mitochondria, and
      the subsequent photodamage of the organelle played an important role in PDT
      mediated apoptosis in myeloid leukemia cells.

PMID- 10911736
TI  - Photosensitization of red blood cell hemolysis by lutetium texaphyrin.
AB  - Lutetium (III) texaphyrin photosensitizes postirradiation or "delayed"
      photohemolysis (DPH) of human and bovine red blood cells at 730 nm by a Type-2
      pathway mediated by singlet molecular oxygen. The DPH rate increases with
      increasing incubation temperature and with the second power of the incident
      fluence. The experimental DPH curves are in good agreement with a multi-hit
      kinetics model based on target theory.

PMID- 10911737
TI  - Photodynamic therapy of human glioma spheroids using 5-aminolevulinic acid.
AB  - The response of human glioma spheroids to 5-aminolevulinic acid (ALA)-mediated
      photodynamic therapy (PDT) is investigated. A two-photon fluorescence microscopy
      technique is used to show that human glioma cells readily convert ALA to
      protoporphyrin IX throughout the entire spheroid volume. The central finding of
      this study is that the response of human glioma spheroids to ALA-mediated PDT
      depends not only on the total fluence, but also on the rate at which the fluence
      is delivered. At low fluences (< or = 50 J cm-2), lower fluence rates are more
      effective. At a fluence of 50 J cm-2, near-total spheroid kill is observed at
      fluence rates of as low as 10 mW cm-2. The fluence rate effect is not as
      pronounced at higher fluences (> 50 J cm-2), where a favorable response is
      observed throughout the range of fluence rates investigated. The clinical
      implications of these findings are discussed.

PMID- 10911738
TI  - UVB-induced epidermal growth factor receptor phosphorylation is critical for
      downstream signaling and keratinocyte survival.
AB  - We have recently shown that UVB radiation activates epidermal growth factor
      receptor (EGFR)/extracellular regulated kinase 1 and 2 (ERK1/2) and p38 signaling
      pathways in keratinocytes. However, the functional relevance of these processes
      for downstream signaling and cell survival remains to be determined. The specific
      EGFR inhibitor PD153035 markedly decreased UVB-induced phosphorylation of EGFR,
      ERK1/2 and shc, whereas p38 activation was unaffected. PD153035 pretreatment
      followed by UVB reduced clonogenic potential and enhanced peroxide production,
      apoptosis and cell death. Our data suggest that ligand-independent
      phosphorylation of EGFR and likely dependent downstream signaling pathways
      regulate cellular defense mechanisms important for cell survival following
      oxidative stress.

PMID- 10911740
TI  - In vivo near-infrared Raman spectroscopy: demonstration of feasibility during
      clinical gastrointestinal endoscopy.
AB  - Raman spectroscopy (RS) has potential for disease classification within the
      gastrointestinal tract (GI). A near-infrared (NIR) fiber-optic RS system has been
      developed previously. This study reports the first in vivo Raman spectra of human
      gastrointestinal tissues measured during routine clinical endoscopy. This was
      achieved by using this system with a fiber-optic probe that was passed through
      the endoscope instrument channel and placed in contact with the tissue surface.
      Spectra could be obtained with good signal-to-noise ratio in 5 s. The effects on
      the spectra of varying the pressure of the probe tip on the tissue and of the
      probe-tissue angle were determined and shown to be insignificant. The limited set
      of spectra from normal and diseased tissues revealed only subtle differences.
      Therefore, powerful spectral-sorting algorithms, successfully implemented in
      prior ex vivo studies, are required to realize the full diagnostic potential of
      RS for tissue classification in the GI.

PMID- 10911739
TI  - Effects of three characteristic amino acid residues of pharaonis phoborhodopsin
      on the absorption maximum.
AB  - Phoborhodopsin (pR or sensory rhodopsin II, sRII) or pharaonis phoborhodopsin
      (ppR or pharaonis sensory rhodopsin II, psRII) has a unique absorption maximum
      (lambda max) compared with three other archaeal rhodopsins: lambda max of pR or
      ppR at ca 500 nm and others at 560-590 nm. Alignment of amino acid sequences
      revealed three sites characteristic of the shorter wavelength-absorbing pigments.
      The amino acids of these three sites are conserved completely among archaeal
      rhodopsins having longer lambda max, and are different from those of pR or ppR.
      We replaced these amino acids of ppR with amino acids corresponding to those of
      bacteriorhodopsin, Val-108 to Met, Gly-130 to Ser and Thr-204 to Ala. The lambda
      max of V108M mutant was 502 nm with a slight redshift. G130S and T204A mutants
      had lambda max of 503 and 508 nm, respectively. Thus, each site contributes only
      a small effect to the color tuning. We then constructed three double mutants and
      one triple mutant. The opsin-shifts of these mutants suggest that Val-108 and Thr
      204 or Gly-130 are synergistic, and that Gly-130 and Thr-204 work additively.
      Even in the triple mutant, the lambda max was 515 nm, an opsin-shift only ca 30%
      of the shift value from 500 to 560 nm. This means that there is another yet
      unidentified factor responsible for the color tuning.

PMID- 10911741
TI  - [Fluorescent in situ hybridization (FISH). Diagnostic aide in certain chromosomal
      anomalies].

PMID- 10911742
TI  - [Fluorescent in situ hybridization (FISH), cytogenetic analytical complement for
      the diagnosis of malignant blood diseases].

PMID- 10911743
TI  - [Quick prenatal diagnosis using FISH in the analysis of non-cultured amniotic
      fluid cells].
AB  - We report our experience with fluorescence in situ hybridization (FISH) on
      uncultured amniocytes and standard cytogenetic analysis. The method have been
      suggested to 259 patients and performed for 199 amniotic fluid samples.
      Commercially available chromosome-specific DNA probes (Aneurysm) for chromosomes
      13, 18, 21, X and Y were used. All full trisomy 18, 21 and monosomy X were
      detected by FISH analysis with exception of one case of mosaic monosomy X. No
      false-positive result was observed. The efficiency, practicability and
      acceptability of the FISH diagnosis are discussed.

PMID- 10911744
TI  - [Diabetes and genetics: significance of intracellular signaling pathways].

PMID- 10911745
TI  - [Multidisciplinary consultation in predictive oncology: experience in Lausanne].

PMID- 10911746
TI  - [The abnormal child: several definitions].

PMID- 10911748
TI  - [Inactivation of the X-chromosome in female mammals].

PMID- 10911747
TI  - [Approach to the abnormal child].

PMID- 10911749
TI  - [Early screening of fetal aneuploidies (c-beta P/us TEST). Report of 600
      observations].

PMID- 10911750
TI  - [Diagnosis, treatment, and familial management of retinoblastoma].

PMID- 10911751
TI  - [Diagnosis of materno-fetal toxoplasmosis].
AB  - The antenatal diagnosis of congenital toxoplasmosis represents today an important
      application of molecular diagnostic methods such as PCR. Done directly in
      amniotic fluid, the PCR for T. gondii is able to detect in utero infected foetus
      with high probability. Doing so, it precludes to obtain foetal blood and to use
      more cumbersome and lengthy procedures such as inoculation to cell lines or to
      mice. Although it is use today in many centres, the molecular diagnosis of T.
      gondii by PCR is neither commercialized nor standardised. The objective of this
      report is to present the methodology used in our institution and to establish its
      degree of validation.

PMID- 10911752
TI  - [Molecular analyses for paternity research and subject identification].

PMID- 10911753
TI  - [Treatment of arterial hypertension and sexual dysfunctions. Is it a certain
      cause of poor treatment compliance?].
AB  - The great interest risen by sildenafil (Viagra) resulted in talking again about
      erectif dysfunction and sexual disorders. Its commercial introduction has already
      renewed speech and social representation about sexuality. Each of the
      antihypertensive drug classes is know to generate sexual disorders. In reducing
      or normalising blood pressure, they decrease intracavernous perfusion pressure,
      already compromised by vascular disease of the hypertensive patient. This is due
      less to a side effect than to the logical consequence of treatment. Analysing
      last 15 years' medical publications shows little interest in searching for sexual
      side effects of hypertensive medication, in both sexes. In its every day
      practice, the physician can more easily have an opinion about their
      repercussions, than by reading studies, with mention of erectile dysfunction
      percentages often lower then the known prevalence in general population. However,
      if we want to improve therapeutic observance, whereas nearly half of the
      hypertensive patients are not compliant, we need to remedy. The solution would be
      improving patient-physician communication and relationship, and preventing
      potentially harmful effects of each antihypertensive agent by proceeding, if
      possible, to a sexually oriented history taking and physical examination before
      and during the treatment. This article reviews the works especially about sexual
      side effects of antihypertensive drug therapy.

PMID- 10911754
TI  - [Disability in the eye of the storm].

PMID- 10911755
TI  - Malaria and complex emergencies.

PMID- 10911756
TI  - Leptospirosis, India. Report of the investigation of a post-cyclone outbreak in
      Orissa, November 1999.

PMID- 10911757
TI  - Progress towards poliomyelitis eradication, South-East Asia, 1998-1999. Part II.

PMID- 10911758
TI  - Who gets priority? Waiting list assessment using a scoring system.
AB  - This study examines the relationship between clinical priority and duration on
      the waiting list. Patients' priority is also compared from three different
      perspectives: the consultant at out-patients (clinical urgency), the general
      practitioner who later sends a letter requesting expedition of admission
      (clinical urgency) and the 18-month waiters. Clinical priority in 222 patients
      awaiting primary hip or knee arthroplasty was assessed using a modification of
      the New Zealand priority criteria scoring system, administered by postal
      questionnaire. There was no correlation between time on waiting list and clinical
      score (r = 0.0). The hip and knee patient scores were not significantly
      different. The mean scores in the consultant and GP groups were higher (greater
      pain and disability) than in the 18-month waiters. The Kappa inter-rater
      agreement method demonstrated that both groups of clinician's assessment of
      clinical urgency had a 'fair' strength of agreement with scoring system, but the
      agreement of the 18-month waiter group was 'very poor'. Time on a waiting list
      should not be a decisive factor in establishing priority for primary hip or knee
      arthroplasty. Scoring systems can aid in assigning clinical priority for
      operation and indeed for the initial out-patient referral.

PMID- 10911759
TI  - Are surgeons aware of the dangers of diathermy?
AB  - Surgical diathermy is an invaluable aid in modern surgery and most contemporary
      diathermy machines are considered safe. However, diathermy accidents do still
      occur and a diathermy unit can be potentially lethal if adequate care is not
      exercised in its use.

PMID- 10911760
TI  - eSurgery.

PMID- 10911761
TI  - Clinical governance and the NHS reforms.

PMID- 10911762
TI  - Why do hospital doctors need MBAs?

PMID- 10911763
TI  - The General Surgery intercollegiate examination and courses.

PMID- 10911764
TI  - Apolipoprotein E mutations, type V hyperlipoproteinaemia and diet.

PMID- 10911765
TI  - Protein-energy undernutrition in hospital in-patients.
AB  - Impaired nutritional status has been frequently reported in surveys estimating
      its prevalence amongst patients in hospital. While there is no doubt that protein
      energy undernutrition has serious implications for health, recovery from illness
      or surgery and hospital costs, lack of nationally or internationally accepted cut
      off points and guidelines for most nutrition-related variables make nutritional
      assessment difficult and proper comparisons between studies impossible. In
      reviewing published work in which the prevalence of undernutrition has been
      assessed, it can be seen that each study defined undernutrition, or nutritional
      risk, using different methodology. This present review aims to highlight the
      problems which arise when deciphering these studies, and the resulting difficulty
      in determining the true prevalence of undernutrition and nutritional risk,
      amongst both general and specific groups of hospital in-patients. It is widely
      agreed that routine hospital practices can further adversely affect the
      nutritional status of sick patients in hospital. How this occurs, and the
      potential effects of impaired nutritional status on clinical outcome are
      examined. The methods currently available to assess nutritional status are
      evaluated in the knowledge that such assessments are difficult in clinical
      practice. The review concludes by proposing that if we want the medical and
      nursing professions to consider the nutritional status of hospital patients
      seriously, definitions of undernutrition and nutritional risk, and cut-off values
      for the nutritional variables measured must be agreed to allow evidence-based
      practice. Outcome measures which allow clear comparisons between groups and
      treatments must be used in studies assessing the effects of nutritional
      interventions.

PMID- 10911767
TI  - Ethanol with a mixed meal increases postprandial triacylglycerol but decreases
      postprandial non-esterified fatty acid concentrations.
AB  - Plasma triacylglycerol concentrations increase after the acute ingestion of
      alcohol (specifically ethanol). However, the effect of ethanol when consumed with
      a mixed meal has not been well studied. The objective of the present study was to
      determine the perturbations of lipid metabolism that occur after ingestion of
      ethanol in combination with a mixed meal of specific fatty acid composition.
      Blood samples were taken from seven healthy male subjects before and after a
      mixed meal, with and without ethanol. The specific fatty acid composition of the
      test meal allowed the fatty acids to be traced into the plasma non-esterified
      fatty acid pool during the postprandial period. Statistical analysis by repeated
      measures ANOVA showed significant effects of ethanol. For example, postprandial
      lipaemia was enhanced after the ethanol test meal compared with the control (P <
      0.05), mainly due to increases in triacylglycerol-rich lipoproteins in the
      flotation range Sf 60-400 (VLDL1) (P < 0.05); those in the range Sf 20-60 (VLDL2)
      and also Sf > 400 (chylomicrons) were not significantly affected. The later
      postprandial increase in plasma non-esterified fatty acid concentrations was
      reduced after the ingestion of ethanol (P < 0.001), but the proportions of
      palmitoleic acid (a marker of fatty acid content of the test meal) and of
      linoleic acid (a marker of endogenous lipolysis) were not affected. The results
      suggest a primary effect of ethanol on the stimulation of secretion of large VLDL
      particles, which then compete for clearance with chylomicrons by lipoprotein
      lipase. The results do not support an effect of ethanol on the release of non
      esterified fatty acid into the plasma. The suppression of plasma non-esterified
      fatty acid concentrations during the postprandial period may contribute towards
      the beneficial effects of moderate ethanol consumption.

PMID- 10911766
TI  - The effect of 677C-->T and 1298A-->C mutations on plasma homocysteine and 5,10
      methylenetetrahydrofolate reductase activity in healthy subjects.
AB  - We have studied the effect of common mutations (677C-->T and 1298A-->C) of the
      methylenetetrahydrofolate reductase (MTHFR) gene in sixty-six healthy French
      subjects, aged 27-47 years. Serum folate, vitamin B12, and plasma total
      homocysteine were measured as well as the specific activity of MTHFR in
      lymphocytes. The frequency of subjects homozygous for the 677TT genotype was 18%,
      and that of those homozygous for the 1298CC genotype was 12.5%. The frequency of
      individuals heterozygous for both mutations was 23.5%. The 1298A-->C mutation was
      associated with decreased MTHFR specific activity in subjects with both 677CC and
      677CT genotypes. This activity was 60% for the 677CC/1298AC genotype and 52% for
      the 677CC/1298CC genotype when compared with the MTHFR specific activity of the
      677CC/1298AA genotype. Heterozygotes for both mutations (677CT/1298AC genotype)
      had 36% of the reference specific activity. Although homocysteine levels in 677TT
      and 1298CC genotype subjects were higher than for other genotypes, no significant
      differences were observed among different genotypes. This may be due to high
      serum folate level in our samples, and suggests that folate therapy may be useful
      to prevent hyperhomocysteinaemia in homozygous mutant subjects.

PMID- 10911768
TI  - Effect of dietary supplements and physical exercise on sensory perception,
      appetite, dietary intake and body weight in frail elderly subjects.
AB  - This present study investigated the effect of a 17-week intervention programme
      with nutrient-dense foods (enriched with vitamins and minerals at 25-100% of the
      Dutch recommended dietary allowance) and/or physical exercise in 159 frail
      elderly subjects (forty-six men, 113 women, mean age 78.7 (SD 5.6) years).
      Subjects were randomized into four groups: (1) control, (2) nutrition
      intervention, (3) exercise or (4) both nutrition intervention and exercise. Main
      outcome variables were sensory perception (smell test and questionnaire),
      appetite (questionnaire), energy intake (3 d food record) and body weight (on a
      weighing scale and with dual energy X-ray absorptiometry measurements). At
      baseline, moderate but significant correlations were found between appetite and
      energy intake (r 0.30, P < 0.0001), between smell test and smell perception
      assessed by questionnaire (r 0.40, P < 0.0001) and between lean body weight and
      energy intake (r 0.50, P < 0.0001). Results after 17-weeks intervention revealed
      neither change in smell test scores (P = 0.19) nor in appetite (P = 0.17). A
      slight positive effect of exercise compared with non-exercising groups on energy
      intake (difference 0.5 MJ, P = 0.05) was shown next to a preserving effect of
      exercise on lean body mass (+0.08 kg) compared with a decrease (-0.4 kg) in non
      exercisers (P < 0.02). The correlation between the change in lean body mass and
      change in energy intake was 0.18 (P = 0.05). In conclusion, an interesting
      preserving effect on lean body mass in frail elderly subjects due to 17 weeks of
      exercise was shown. Since a decline in lean body mass was observed in the non
      exercisers, effects may be attributable to change in activity pattern. Changes in
      lean mass were also slightly, but significantly, correlated with changes in
      energy intake. In turn, energy intake was not related to a change in reported
      appetite or sensory perception. Nutrient-dense foods were not able to improve any
      of the outcome variables in this study.

PMID- 10911769
TI  - Dietary fat clearance in type V hyperlipoproteinaemia secondary to a rare variant
      of human apolipoprotein E: the apolipoprotein E3 (Arg 136-->Ser)
AB  - This present case report describes two siblings with severe type V
      hyperlipoproteinaemia, diagnosed very early in life and due to the combination of
      the common apolipoprotein (Apo) E2 allele and rare mutant variant of ApoE, ApoE3
      (Arg 136-->Ser). Phenotyping of ApoE falsely identified E2/E2 phenotype. The
      presence of mutated ApoE was suspected on an unusual restriction polymorphism of
      a Hha 1 restriction site and confirmed by sequence analysis of the cloned
      polymerase chain reaction fragment of exon 4 and familial segregation study. The
      severity of the hypertriacylglycerolaemia was modulated by the lipid content of
      the diet. A low-fat diet enriched in medium-chain triacylglycerol (TAG) decreased
      but did not normalize plasma TAG levels in both affected patients of the
      pedigree. A standardized lipid-enriched test meal showed a marked impairment of
      TAG-rich lipoprotein (TRL) clearance, especially the exogeneous TRL bearing ApoB
      48 which still represented 79% of total TRL 7 h after the fat load. Finally,
      differences between the male and female siblings with the existence of a
      consanguine relationship in their parents suggested the involvement of other
      genetic factors in modulating the severity of phenotypic expression. This
      observation reinforces the usefulness of genotyping of ApoE for the
      characterization of genetic hypertriacylglycerolaemia and selection of the
      appropriate diet and treatment.

PMID- 10911770
TI  - The physical state of a meal affects hormone release and postprandial
      thermogenesis.
AB  - There is evidence that food consistency may influence postprandial physiological
      responses. Recently we found that homogenization of a vegetable-rich meal
      significantly delayed the gastric emptying rate and was more satiating than the
      same meal in solid-liquid form. In this present study we investigated whether
      homogenization also influences endocrine and metabolic responses to the meal.
      Eight healthy men, aged 21-28 (mean 24.5) years, were given the meal (cooked
      vegetables 250 g, cheese 35 g, croutons 50 g and olive oil 25 g, with water 300
      ml; total energy 2.6 MJ) in both solid-liquid (SM) and homogenized (HM) form, in
      random order, at 1-week intervals. Variables assayed were plasma glucose, insulin
      and glucose-dependent insulinotropic peptide (GIP) levels for 2 h and diet
      induced thermogenesis (DIT) for 5 h. Plasma glucose pattern was similar after
      both meals. However, HM induced significantly greater insulin, GIP and DIT
      responses than SM. Mean integrated areas under the curves (AUC) were 1.7 (SEM
      0.38) v. 1.2 (SEM 0.33) U/l per 120 min (P = 0.005) for insulin, 19.9 (SEM 2.44)
      v. 16 (SEM 1.92) nmol/l per 120 min (P = 0.042) for GIP, and 237.7 (SEM 16.32) v.
      126.4 (SEM 23.48) kJ/300 min (P = 0.0029) for DIT respectively. Differences
      between GIP-AUC after HM and SM correlated significantly with differences between
      insulin-AUC after HM and SM (r2 0.62, P = 0.021). These findings demonstrate that
      homogenization of a meal results in a coordinated series of changes of
      physiological gastroentero-pancreatic functions and confirm that the physical
      state of the meal plays an important role in modulating endocrine and metabolic
      responses to food.

PMID- 10911772
TI  - Effect of whole linseed (Linum usitatissimum) in the diet of finishing pigs on
      growth performance and on the quality and fatty acid composition of various
      tissues.
AB  - Pigs (n 144, 30 kg liveweight) were allocated to one of three diets differing in
      the level of whole linseed (Linum usitatissimum, also known as flaxseed). The
      diets contained 0, 50 and 100 g/kg for diets L0, L50 and L100 respectively, while
      containing a constant oil content (60 g/kg). Pigs were slaughtered at a
      liveweight of 77-87 kg. With the exception of a slight difference in feed intake,
      there was no effect of diet on production characteristics or carcass traits.
      Levels of alpha-linolenic acid were increased in all tissues studied as the
      amount of linseed in the diet increased. In the plasma, m. longissimus thoracis,
      liver and kidney eicosapentaenoic acid concentration increased markedly.
      Docosapentaenoic acid concentration increased in the muscle, liver and kidney,
      whereas in the plasma higher levels of docosahexaenoic acid were observed. None
      of the longer-chain fatty acids (C20 or longer) were detected in the subcutaneous
      fat. The changes in fatty acid composition resulted in marked changes to the n-6:
      n-3 and arachidonic: eicosapentaenoic acid ratios. Feeding whole linseed had no
      negative effect on the oxidative stability of the meat. Sensory panel results
      showed no significant differences by diet except for a reduction in abnormal
      odour (odour perceived by panellists to be abnormal in pigmeat) in the L50 diet
      and a reduction in the skatole odour (odour of 3-methylindole) in the pigs fed on
      diet L100. It is concluded that increasing the linseed content of pig diets up to
      100 g/kg has no adverse effect on the carcass or meat quality whilst enhancing
      the levels of n-3 fatty acids which have a potentially positive health effect in
      man.

PMID- 10911771
TI  - Lack of effect of supplementation with essential fatty acids on bone mineral
      density in healthy pre- and postmenopausal women: two randomized controlled
      trials of Efacal v. calcium alone.
AB  - Randomized controlled trials of the effects of the dietary supplement Efacal
      (Scotia Pharmaceuticals Plc, Guildford, Surrey, UK) v. Ca only on total body bone
      mineral density (BMD) and markers of bone turnover were conducted in healthy pre-
      and postmenopausal women separately. Total daily dose for 12 months for the
      Efacal groups was: Ca 1.0 g, evening primrose oil 4.0 g and marine fish oil 440
      mg; and for the control groups was: Ca 1.0 g. Reported compliance was better than
      90% in both age groups. For the forty-three premenopausal women (age range 25-40
      years), initial mean total body BMD values were similar for Efacal and control
      groups and both groups showed highly significant mean increases of about 1%;
      however, there were no significant between-group differences for the changes in
      BMD or markers of bone turnover. For the forty-two postmenopausal women (age
      range 50-65 years), initial mean total body BMD values were again well-matched
      across treatment groups. Both Efacal and control groups showed highly significant
      decreases in total body BMD of about 1%, but again there were no significant
      between-group differences in total body BMD or markers of bone turnover. Possible
      confounding variables such as initial total body BMD were explored but had no
      effect on the outcome in either age group. Nail quality improved in both age
      groups and in both Efacal and control groups. Again, there was no significant
      difference between treatment groups. No evidence was found to support a
      beneficial effect of Efacal on BMD in these women.

PMID- 10911773
TI  - Glucose-insulin relationships and thyroid status of cockerels selected for high
      or low residual food consumption.
AB  - The plasma glucose-insulin relationships and thyroid status were investigated in
      two lines of adult cockerels divergently selected for high (R+) or low (R-)
      residual food consumption (RFC). For a given body weight, R+ birds had a 74%
      higher food intake than R- birds. Plasma glucose concentrations were
      significantly lower in the R+ line compared with the R- when fasted, whereas R+
      birds exhibited a significantly lower plasma insulin concentration than R- birds
      either in fed or fasted state. After an overnight fast, R+ birds also exhibited a
      higher sensitivity to exogenous insulin in view of its more pronounced
      hypoglycaemic effect. After an oral glucose load, the glucose disposal of R+
      cockerels was faster despite lower glucose-induced plasma insulin concentration.
      Whilst plasma triacylglycerol concentrations were lower in the R+ line when fed,
      plasma non-esterified fatty acid concentrations were higher in fasted R+ than R-
      cockerels (684 v. 522 mumol/l). Higher plasma triiodothyronine concentrations
      were observed in fed R+ compared with R- birds (3.0 v. 2.1 nmol/l respectively).
      The higher plasma concentrations of triiodothyronine associated with lower
      concentrations of insulin could account for the leanness and the elevated diet
      induced thermogenesis previously observed in the R+ line.

PMID- 10911774
TI  - Dietary low-glucosinolate rapeseed meal affects thyroid status and nutrient
      utilization in rainbow trout (Oncorhynchus mykiss).
AB  - Two rapeseed (Brassica napus) meals, RM1 and RM2, with two levels of
      glucosinolates (GLS; 5 and 41 mumol/g DM respectively) were incorporated at the
      levels of 300 and 500 g/kg of the diets of juvenile rainbow trout (Oncorhynchus
      mykiss) in replacement of fish meal, and compared with a fish-meal-based diet. A
      decrease in the digestibility of the DM, protein, gross energy and P was observed
      with high-rapeseed meal (RM) incorporation. In trout fed on RM-based diets,
      growth performance was reduced even after only 3 weeks of feeding. Feed
      efficiency was adversely affected by RM and GLS intake. Protein and energy
      retention coefficients were significantly lower in fish fed on the diet
      containing the higher level of GLS. P retention was significantly lower with all
      the RM-based diets than with the fish-meal diet. Irrespective of the degree of
      growth inhibition, fish fed on RM-based diets exhibited similar typical features
      of hypothyroid condition due to GLS intake, expressed by lower plasma levels of
      triiodothyronine and especially thyroxine and a hyperactivity of the thyroid
      follicles. This hypothyroidal condition led to a strong adjustment of the
      deiodinase activities in the liver, the kidney and the brain. A significant
      increase of the outer ring deiodinase activities (deiodinases type I and II
      respectively) and a decrease of the inner ring deiodinase activity (deiodinase
      type III) were observed. It is concluded that the observed growth depression
      could be attributed to the concomitant presence of GLS, depressing the thyroid
      function, and of other antinutritional factors affecting digestibility and the
      metabolic utilization of dietary nutrients and energy.

PMID- 10911775
TI  - High-fat diets affect the expression of nuclear retinoic acid receptor in rat
      liver.
AB  - The purpose of this study was to differentiate between the effects of the amount
      and the type of dietary lipids on the expression of the retinoic acid receptor
      (RAR), but also the peroxisome proliferator-activated receptor (PPAR) and the
      receptor of the 9-cis retinoic acid (retinoid X receptor (RXR)) in rat liver. Six
      groups of eight rats (5-weeks old) were fed during 4 weeks on the following
      diets: control 50 g vegetable oil/kg, high-fat diet 250 g vegetable oil/kg. These
      oils were either coconut oil (rich in saturated fatty acids) or olive oil (rich
      in monounsaturated fatty acids) or safflower oil (rich in polyunsaturated fatty
      acids, mainly as n-6). The three high-fat diets induced a significant decrease of
      the maximal binding capacity of RAR and of the abundance of RAR beta mRNA.
      Simultaneously, an increased expression of PPAR alpha mRNA was observed while no
      significant difference on abundance of RXR alpha mRNA was observed. The
      mechanisms involved are probably multiple, but one hypothesis is that a
      modification of the equilibrium between the nuclear receptors, resulting from an
      increased expression of PPAR, induces a decreased expression of RAR in rat liver.

PMID- 10911776
TI  - The effect of high intakes of casein and casein phosphopeptide on calcium
      absorption in the rat.
AB  - The effect of the level or source of dietary protein or protein-derived peptides
      on Ca absorption is not well understood. We determined, therefore, the influence
      of habitual dietary casein level, meal casein and meal casein phosphopeptide
      (CPP) on Ca absorption in the rat. True fractional Ca absorption was investigated
      in male 7-week-old rats, Wistar strain, in three separate studies using a faecal
      47Sc: 47Ca ratio method. In studies A and C, rats (n 8 per group) were fed on a
      purified diet containing 200 g casein/kg for 2 weeks. Rats were then given a 47Ca
      labelled meal (10 g) containing (per kg) either 0, 100, 200, or 300 g casein
      (study A) or 0, 100, 200, 350 or 500 g CPP (study C). In study B, rats (n 24 per
      group) were fed on a purified diet containing (per kg) either 200, 350 or 500 g
      casein for 2 weeks. Each group was then further randomized into three groups (n 8
      per group) and given a 47Ca-labelled meal (10 g of the same diet) containing (per
      kg) either 200, 350 or 500 g casein. Ca absorption from a meal was unaffected by
      increasing meal casein concentration from 0 to 300 g/kg (study A), but was
      increased with a meal casein content of 500 g/kg (study B). Fractional Ca
      absorption decreased with increasing usual dietary casein intake in the range 200
      500 g/kg (study B), suggesting intestinal adaptation. Ca absorption was
      unaffected by inclusion of 100 g CPP/kg in a single meal but was significantly (P
      < 0.001) reduced by 200, 350 and 500 g CPP/kg meal, with no evident dose
      relationship. Thus, while Ca absorption was enhanced by high-casein meals, the
      mechanism remains unclear.

PMID- 10911777
TI  - Sedation, safety and MRI.

PMID- 10911778
TI  - Ethical issues in teleradiology.
AB  - Teleradiology is the electronic transmission of radiographic images from one
      geographic location to another for the purposes of diagnosis and/or consultation.
      It raises interesting ethical and practical issues which have received relatively
      little attention in the radiology or ethics literature to date. These include
      confidentiality, data security and technological reliability, consent,
      competence, interprofessional and professional-patient relationships, and the
      organization of medical services. This paper reviews these issues, discussing how
      far these are new concerns in radiological practice, and makes suggestions for
      minimum ethical and professional standards for teleradiological practice.

PMID- 10911779
TI  - The characteristics and significance of thoracic lymphadenopathy in parapneumonic
      effusion and empyema.
AB  - The occurrence of significant mediastinal lymphadenopathy together with pleural
      effusion or empyema inevitably raises concern about the presence of intrathoracic
      malignancy or granulomatous disease. Lymph node enlargement may also occur when
      pneumonia is accompanied by a parapneumonic effusion or empyema. Features that
      allow "benign" lymph node enlargement to be distinguished from malignant causes
      have not previously been determined. The present study aims to establish the CT
      characteristics of enlarged nodes in parapneumonic effusion. The appearances of
      mediastinal lymph nodes were recorded in 50 consecutive patients with
      parapneumonic effusion/empyema. 18 (36%) had mediastinal lymphadenopathy (node
      size greater than 1 cm). The mean number of enlarged nodes was 1.9 (range 1-3)
      and the mean size was 1.4 cm (2 cm maximum). Seven patients had a single involved
      site, nine patients two sites and two patients three sites. The right
      paratracheal area was most commonly involved and the subcarinal area contained
      the largest nodes. The presence of enlarged nodes did not correlate with
      biochemical and microbiological stage of pleural infection, length of history, or
      extent of consolidation. This study shows that mediastinal lymphadenopathy is
      commonly associated with parapneumonic effusion and that multiple sites may be
      involved. The degree of enlargement is moderate although lymphadenopathy of
      greater than 2 cm size should raise the possibility of other pathology.

PMID- 10911780
TI  - Systemic and regional haemodynamic effects of aortofemoral angiography.
AB  - The aim was to investigate the regional and systemic haemodynamic consequences of
      bolus injection of fluids with different physical properties in the course of
      routine aortography. Iopamidol was compared with an equiosmolar solution of
      mannitol and with a 0.9 N saline solution. Continuous blood flow and Pulsatility
      Index (PI), as an index of regional vascular resistance, were measured by Doppler
      technique. Finger arterial pressure and heart rate were monitored at the time and
      for 3 min following each intraaortic bolus injections. The patients who underwent
      routine aortography were grouped according to the site of the flow measurements:
      common femoral artery, common carotid artery and brachial artery. Flow changes
      induced by the bolus infusion were evident for all the fluids but only at the
      femoral artery level. After an immediate (3 +/- 2 s) and brief (2 +/- 2 s) but
      marked reduction of flow and in-phase increase of PI following the bolus, further
      haemodynamic changes were observed only in the femoral artery, with a peak at 35
      +/- 10 s and returning to baseline values after 70 +/- 15 s, in terms of both
      increased mean blood velocity and decreased PI. Saline and mannitol induced
      overall blood velocity alterations of 54% and 80%, respectively, and PI
      reductions of 44% and 57% compared with those induced by iopamidol. In the other
      vascular areas there was only a 17 +/- 2% increase of the physiological early
      diastolic backflow at the brachial artery level. Blood pressure decreased and
      heart rate increased in phase with the flow changes of the femoral artery. IN
      CONCLUSION: (1) a dramatic rheodynamic perturbation at the site of injection
      induces a vasodilating stimulus; (2) the haemodynamic response following
      injection results in marked vasodilation of only the tributary vascular bed; (3)
      flow steal may occur from other beds towards the lower limb vascular beds owing
      to vascular impedance imbalance; (4) a reduction of systemic arterial pressure is
      induced in phase with the regional vascular events and a reflex increase of the
      heart rate; and (5) the physical properties of the injected fluids influence the
      intensity of the perturbation, although the decisive triggering factor is the
      counterflowing bolus per se.

PMID- 10911781
TI  - Granularity of the carotid artery intima-medial layer: reproducibility of
      quantification by a computer-based program.
AB  - Ultrasound of the carotid artery identifies the hypoechoic intima-medial layer
      (IML). Increased granularity of the IML has been associated with early
      atherosclerosis. The aim of the study was to assess the reproducibility and
      observer agreement of a computer-based program measure of IML granularity. Ten
      healthy adult volunteers (median age 32 years, range 18-34 years) were examined
      twice, 2 weeks apart, with a 7 MHz linear transducer using standardized imaging
      settings, by two observers. Images of both common carotid arteries were digitized
      and analysed on a customized computer program. The ratio (averaged over a 1 cm
      length of arterial wall) of the lowest pixel brightness in the IML to the maximum
      pixel brightness in the intima-medial interface was determined. Overall mean
      intima-medial reflectivity (IMR) indices for the two observers were 0.761 +/-
      0.101 and 0.707 +/- 0.103, with single determination standard deviation values of
      0.090 and 0.073, respectively. For interobserver calculations, the overall mean
      IMR index for both sessions was 0.734 +/- 0.107, with a single determination
      standard deviation of 0.067. Comparison with the intima-medial thickness (IMT)
      showed an inverse correlation (r = -0.72). This method of quantifying the
      reflectivity of the IML demonstrates good reproducibility in subjects with normal
      IMT measurements. The technique may be of value in identifying subjects at high
      risk of atherosclerosis but with IMT still within the normal range.

PMID- 10911782
TI  - In vivo degradation of tungsten embolisation coils.
AB  - It has been suggested that tungsten embolisation coils in intracranial aneurysms
      may dissolve in situ. These coils are also used, in much larger quantities, for
      the occlusion of larger vessels outside the cranium. This study was performed to
      investigate whether tungsten embolisation coils may become degraded in vivo and
      to examine whether this is radiographically evident on medium-term follow-up. 10
      patients who had undergone aortic stent-graft repair of an abdominal aortic
      aneurysm (8 male and 2 female, mean age 69.7 years) and 10 age- and sex-matched
      controls were studied. The study group had also received an average of 64 cm of
      tungsten coil either to prevent or to treat an endoleak. Whole blood, serum and
      urine tungsten levels were assayed. Immediate post-operative and follow-up
      abdominal radiographs were reviewed by two consultant vascular radiologists to
      detect visible changes in the coils. Whole blood, serum and urine levels of
      tungsten were highly and significantly elevated (p < 0.001) in the study group
      compared with the controls. No radiographic changes in the coils were seen at an
      average of 16.7 months. In conclusion, tungsten embolisation coils dissolve in
      humans but radiographic changes are not apparent on medium-term follow-up. The
      clinical significance of these findings is uncertain but long-term follow-up is
      needed.

PMID- 10911784
TI  - Improving radiographer highlighting of trauma films in the accident and emergency
      department with a short course of study--an evaluation.
AB  - The case for radiographer abnormality highlighting in the Accident and Emergency
      (A&E) department is well documented. Following evaluative feedback, 280
      questionnaires were sent nationally to A&E radiology departments (excluding
      Northern Ireland). The intent of the survey was to ascertain the viability of
      constructing a short course in trauma plain film pattern recognition in the axial
      and appendicular skeleton. Following a highly positive response a course was
      designed and operated on a workshop basis, being lead primarily by reporting
      radiographers. The course was evaluated for effectiveness using three identical
      assessments of 42 films, including 12 positive for trauma. A sample of 22
      radiographers who attended the pilot course and subsequent courses throughout
      1998/99 undertook the assessment. The assessments themselves were performed at
      the start and end of the course and 6-10 weeks after completion. Results appear
      to indicate that a significant improvement in the specificity (p = 0.002) and
      accuracy (p = 0.005) was achieved following the course. In the light of
      continuing professional development, the course appears to address the needs of
      the majority of clinical radiographers working in A&E.

PMID- 10911783
TI  - The value of intubation dacryocystography after dacryocystorhinostomy.
AB  - We retrospectively reviewed 104 dacryocystograms carried out on 72 patients who
      had previously undergone dacryocystorhinostomy, to assess the diagnostic
      contribution of the radiological investigation in patients with persistent or
      recurrent symptoms. In patients whose symptoms were referable to the operated
      side, dacryocystography was performed as part of further pre-operative
      assessment. In 42% of these patients it demonstrated an anatomical or
      physiological abnormality that explained the symptoms. However, no clear reason
      for the recurrence of symptoms was demonstrated in 58% of cases.

PMID- 10911785
TI  - A comparison of fixed and variable kVp technique protocols for film-screen
      mammography.
AB  - Mammographic image quality, contrast and dose for a variable tube potential (kVp)
      technique protocol for film-screen mammography have been investigated. In this
      protocol, the tube potential is increased for larger breast thicknesses.
      Comparisons were made with fixed kVp protocols, in which the tube potential is
      kept constant and the breast thickness compensated for by prolonging the exposure
      ("fixed kVp" protocol). All measurements were performed on a mammography unit
      with a molybdenum target and filter. Image quality was quantified by image
      contrast, image detail detection and the minimum detectable dimension of low
      contrast objects. It was demonstrated that for a compressed breast thickness of
      less than about 40 mm, varying the tube potential had a negligible effect upon
      dose but a significant effect upon image quality. For a compressed breast
      thickness greater than about 60 mm, the effect of the tube potential upon image
      quality was much reduced; however, the effect upon dose was significantly
      greater. The variable kVp protocol takes advantage of this feature to yield a
      significantly lower dose for thicker breasts with a small reduction in image
      quality, often only within experimental uncertainty. For an exposure under
      automatic exposure control, increasing the tube potential from 26 kVp to 30 kVp
      for a breast of a reference tissue composition (50% adipose and 50% glandular)
      with a compressed thickness of 60 mm reduced the mean glandular dose from 6 mGy
      to 3.9 mGy (-35%), but increased the minimum detectable dimension of a low
      contrast mass from 0.8 (+/- 0.1) mm to 1.1 (+/- 0.1) mm. Adopting a variable kVp
      protocol led to a median patient mean glandular dose per film of 2.7 mGy, nearly
      independent of compressed breast thickness. In our survey, the mean age of women
      presenting for mammography is younger and the mean compressed breast thickness is
      less than reported from screening centres. This suggests that there will be a
      higher proportion of denser, glandular tissue in the breasts incorporated within
      this survey than for surveys from screening centres. The clinical use of the
      variable kVp protocol allows the extraction from patient data of separate changes
      in breast composition which are due to patient age and breast thickness. It is
      concluded that the reference breast tissue composition is not an accurate
      representation of the women presenting at this centre.

PMID- 10911786
TI  - False positive 131I whole body scans in thyroid cancer.
AB  - Well differentiated thyroid cancer is a rare disease in the UK. It is the only
      cancer which, having metastasized, remains curable by radioisotope therapy with
      131I. The main indication for administering repeat doses of 131I is the
      appearance of abnormal uptake in a whole body scan following diagnostic or
      therapeutic 131I administration. False positive scans, showing the presence of
      131I uptake in the absence of residual thyroid tissue or metastases can occur,
      although they are uncommon. Unless recognized as a false positive, 131I uptake
      may result in diagnostic error and lead to administration of an unnecessary
      therapy dose. We describe a series of nine patients in whom the scans showed
      false positive uptake of 131I, including cases where the cause of the uptake is
      still uncertain. We demonstrate the common sites of false positive uptake,
      discuss the underlying mechanisms and suggest a systematic approach to the
      interpretation of whole body scans in order to prevent unnecessary treatment with
      131I.

PMID- 10911787
TI  - Thyroid dosimetry in Europe following the Chernobyl accident.
AB  - Thyroid dose estimates for European populations following the Chernobyl accident
      in 1986 have been presented in the literature. These dose estimates used standard
      values for parameters such as thyroid mass, iodine uptake and biological half
      life. Previous work has shown that these values are not representative of
      European populations and that local values should be utilized. Using published
      data on revised thyroid dose estimates, thyroid dosimetry data arising as a
      result of the Chernobyl accident are presented for 22 European countries. When
      these are compared with previously published estimates it is found that in all
      cases the previous results underestimate the thyroid dose by up to a factor of 4.
      Risk estimates on the incidence of fatal and non-fatal thyroid cancers are also
      determined from this new data and, again, the results are underestimated. The
      results show an increase in the number of fatal cancers, rising from 149 as
      predicted by the NEA to 310 under the new estimates, and from 180 as predicted by
      UNSCEAR to the new estimate of 380.

PMID- 10911788
TI  - Experimental determination of practical peak voltage.
AB  - In diagnostic radiology the practical peak voltage was initially derived by
      postulating that, for a given combination of X-ray tube and contrast geometry, a
      constant X-ray tube voltage should produce the same low level contrast as an
      arbitrarily pulsating X-ray tube voltage. It has been shown previously that the
      practical peak voltage can be properly defined as a weighted average of the X-ray
      tube voltage. Up to now the concept of practical peak voltage was based entirely
      on the results of calculations. The present paper describes the experimental
      investigations for measuring and comparing the contrast-equivalent X-ray tube
      voltage and practical peak voltage derived from an invasive measurement of the
      time-dependent X-ray tube voltage. Within the experimental uncertainties, the
      results demonstrate the mutual equivalence of the practical peak voltage and the
      contrast-equivalent X-ray tube voltage.

PMID- 10911789
TI  - The need for the moving junction in craniospinal irradiation.
AB  - The moving junction is used in craniospinal irradiation (CSI) to smooth out any
      dose inhomogeneity across the head/spine junction. The aim of this study was to
      demonstrate the extent of the head/spine junction inhomogeneity in treatment
      plans of actual patients and to compare stationary and moving junction data. The
      radiotherapy plans, prescriptions and case notes of 18 patients (12
      medulloblastomas, 3 supratentorial primitive neuroectodermal tumours, 2
      pineoblastomas and 1 pineal germinoma) treated with CSI (35 Gy in 21 fractions
      over 29 days) were examined. At 16 months median follow-up (range 1.5-35.5
      months), no junctional recurrences or myelopathy were observed. Using the moving
      junction technique the mean maximum anterior cord dose, from 5 cm caudal to 3 cm
      cephalad of the Day 1 junction, was 36.3 Gy, and the mean minimum anterior cord
      dose was 32.9 Gy, with a mean within-patient variation of 3.4 Gy (9.7% of 35 Gy).
      In four patients, comparison of dose variation across the field junction was made
      between the original plans and a re-plan using a stationary junction. The effect
      of a matched junction, a 2 mm overlap and a 2 mm gap were studied both for moving
      junction and stationary junction techniques. Dose variations were similar in all
      cases for exactly-matched fields, but for a 2 mm overlap or gap the dose
      variation was smaller in all but one case for the moving junction technique.
      These data suggest that the moving junction is important to minimize the risk of
      overdose or underdose across the spine/head junction in CSI.

PMID- 10911790
TI  - The curved needle technique for accessing the L5/S1 disc space.
AB  - Bending the guide needle has been suggested as an alternative technique that may
      improve the success rate for accessing the L5/S1 level on discography. We
      performed a prospective randomized study to compare this technique with the use
      of a conventional straight needle. There was a significantly lower failure rate
      using the curved needle (p < 0.05). The incidence of nerve root impingement was
      also lower.

PMID- 10911791
TI  - Intraosseous pneumatocyst of the scapula.
AB  - Intraosseous pneumatocyst is a gas-containing cyst-like lesion that occurs most
      frequently in the ilium, sacrum or vertebrae. We present a case involving the
      left scapula that was found incidentally on CT. To our knowledge, intraosseous
      pneumatocyst of the scapula has not been previously reported.

PMID- 10911792
TI  - Perianal mucinous carcinoma successfully treated with a combination of external
      beam radiotherapy and high dose rate interstitial brachytherapy.
AB  - The case of an 84-year-old man with perianal mucinous carcinoma is presented. The
      tumour was 6 cm in diameter and extended into the surrounding tissues. Taking the
      patient's advanced age and disease into account, rectosigmoidectomy and colostomy
      were carried out without resection of most of the tumour. Radiotherapy consisted
      of pre-operative external beam radiotherapy (EBRT) of 40 Gy in 20 fractions, post
      operative EBRT of 24 Gy in 12 fractions, and high dose rate interstitial
      brachytherapy of 12 Gy in a single fraction. The patient tolerated the entire
      course of radiotherapy well. The patient is doing well without regrowth or
      complications 7 years after radiotherapy. To our knowledge, there have been no
      reports on the successful outcome of radiotherapy for perianal mucinous
      carcinoma. This case suggests that a combination of EBRT plus interstitial
      brachytherapy boost may play a role in the definitive treatment of perianal
      mucinous carcinoma.

PMID- 10911793
TI  - Pitfalls of breast MRI.
AB  - This article reviews some of the common pitfalls associated with breast MRI.
      Pitfalls can be broadly considered as "technical" (relating to patient factors or
      machine factors, which can influence image interpretation) or "non-technical"
      (relating to misinterpretation of imaging findings in the absence of technical
      problems). Awareness of potential pitfalls is important if MRI is to maximize its
      potential in breast imaging.

PMID- 10911794
TI  - Art for art sake, but is it legal?

PMID- 10911795
TI  - A lady with chronic left hypochondrial pain.

PMID- 10911796
TI  - Anaplastic large cell lymphoma: what's in a name?

PMID- 10911797
TI  - Problematic pigmented lesions: approach to diagnosis.
AB  - A number of pigmented lesions are difficult to classify and raise the possibility
      of a melanoma diagnosis. Care should be exercised to exclude non-melanocytic
      lesions, and benign melanocytic entities, both of which can mimic melanoma
      histologically. In addition, the possibility of the lesion being a melanoma
      variant or epidermotropic metastasis should be considered. There will still be
      some cases that are difficult to resolve. These usually fall into one of three
      categories: atypical junctional melanocytic lesion versus early melanoma; naevus
      versus naevoid melanoma; and atypical Spitz, cellular blue, and deep penetrating
      naevi versus thick melanoma. These will pose problems even for experts. The
      atypical Spitz lesions are perhaps the most important category because they tend
      to be from younger individuals, the differential diagnosis is thick melanoma, and
      there is no single discriminating histological feature.

PMID- 10911798
TI  - Neonatal thrombosis.

PMID- 10911800
TI  - Acp. Best practice no 160. Renal biopsy specimens.
AB  - Taking a kidney biopsy is not a trivial procedure. The sample is almost
      invariably smaller than the pathologist would like. Investigation usually
      requires division into even smaller samples to permit the application of
      specialist techniques. In some cases the biopsy is taken not for diagnosis, but
      to assess the extent of tissue damage. The clinical need is sometimes extremely
      urgent. These features all underline the crucial importance of collaboration
      between pathologist and nephrologist if maximum benefit is to be obtained from
      such very small samples. Consequently, in deciding what to do with a renal
      biopsy, flexibility and thought are required rather than a single prescribed list
      of procedures. This article, written after extensive international consultation,
      represents an attempt to define current best practice in the laboratory handling
      of renal biopsy specimens, while not neglecting the need to tailor processing to
      the individual needs of each case.

PMID- 10911801
TI  - The borderline cervical smear: colposcopic and biopsy outcome.
AB  - AIMS: To review the outcome of women referred with smears showing borderline
      nuclear change (BNC), and to determine any differences in outcome if BNC was
      persistent, preceded by dyskaryosis, or followed treatment for cervical
      intraepithelial neoplasia (CIN). In addition, to determine criteria that might
      permit delineation of a BNC subtype, predictive of CIN. METHODS: The records of
      178 women referred for colposcopy in 1993, with last smear showing BNC, were
      obtained from our laboratory database. The cytology, colposcopy, and biopsy
      follow up for a five year period were also obtained. The patients were divided
      into three categories according to their smear status before the last referral
      borderline smear: category 1, persistent BNC (n = 39); category 2, BNC preceded
      by dyskaryotic smears (n = 100); and category 3, BNC after treatment for CIN (n =
      39). The referral borderline smears were reviewed on cases with negative outcome
      and those with a biopsy diagnosis of CIN2 and CIN3. RESULTS: In 50 women (28%) no
      biopsy was deemed necessary after colposcopic assessment. The biopsy results in
      the remaining 128 (72%) women were as follows: normal in 18 (10%), koilocytosis
      in 12 (7%), CIN1 in 45 (25%), CIN2 in 32 (18%), and CIN3 in 21 (12%) women. High
      grade lesions (CIN2, CIN3) were seen on biopsy in 14 of 39, 33 of 100, and six of
      39 cases in category 1, category 2, and category 3, respectively. Blind review of
      the referral borderline smears from 53 women with a biopsy diagnosis of high
      grade lesions (32 CIN2, 21 CIN3) confirmed they were borderline in 23, upgraded
      them to mild dyskaryosis in 15, and found that 14 cases of isolated moderate or
      severe dyskaryotic cells had been missed originally. The borderline change was in
      mature squamous cells in five of 23 and in immature metaplastic epithelium in 18
      of 23 cases. After smear review in 68 women with negative outcome, 36 smears were
      reclassified as negative in keeping with inflammation and atrophy, three were
      considered unsatisfactory, one was upgraded to CIN1, and 28 were confirmed as
      BNC. Of the latter, 25 of 28 were in mature squamous cells. The five year follow
      up on women with negative colposcopy (n = 50), negative loop excision of
      transformation zone (LETZ) (n = 18), and LETZ with koilocytosis (n = 12) showed
      subsequent high grade CIN on LETZ in 16, 0, and two patients, respectively.
      CONCLUSIONS: On referral of women for colposcopy with last smear showing BNC, the
      outcome was high grade CIN in over 30% of cases, irrespective of whether the
      borderline smear was preceded by another borderline smear or by a dyskaryotic
      smear. In contrast, in those referred because of BNC after treatment of CIN, high
      grade CIN was seen less frequently (15% of cases). Furthermore, in cases that
      necessitated loop excisions, high grade CIN was seen in 41%. This study also
      showed that BNC associated with inflammation or atrophy, or BNC in mature
      squamous cells, appears to have lower predictive value for CIN than those cases
      where BNC is associated with immature metaplastic epithelium. The use of terms
      such as "BNC favour reactive" for the former and "BNC favour dyskaryosis" for the
      latter is recommended, together with follow up by cytology and colposcopy,
      respectively.

PMID- 10911799
TI  - The use of laboratory tests in the diagnosis of SLE.
AB  - ANA IIF is an effective screening assay in patients with clinical features of SLE
      and will detect most anti-ssDNA, anti-dsDNA, ENAs, and other autoantibodies.
      False positives are common. The clinical importance cannot be extrapolated from
      the ANA titre or pattern, although higher titres (> 1/160) are more likely to be
      important. HEp-2 cells are the most sensitive substrate for ANA detection, but
      this must be balanced against an increased incidence of insignificant positivity.
      ANA positive samples should be subjected to more specific assays for the
      diagnosis of SLE. A combination of ENA (Ro/La/Sm/RNP) and dsDNA assays will
      detect most patients with SLE as long as the characteristics of the assays used
      are well understood. ESR and CRP measurements provide useful additional
      information. Sjogren's syndrome and MCTD will produce overlapping serology with
      SLE, and anti-dsDNA titres are sometimes seen in autoimmune hepatitis and
      rheumatoid arthritis. All results should be reported in the light of the clinical
      details, by an experienced immunologist. A suggested diagnostic protocol is
      outlined in fig 1. The type of assay used crucially influences the predictive
      value of the tests. ELISA technology dominates routine laboratory practice, but
      tends to produce more false positive and true weak positive results, which may
      reduce the PPV of the test. This can be minimised by using IgG specific
      conjugates and careful assay validation. The NPV for SLE [figure: see text] is
      high for most assays but the PPV varies. Where necessary, laboratories should use
      crithidia or Farr dsDNA assays to confirm dubious ELISA dsDNA results, and ID/IB
      to confirm dubious ENA results. For monitoring, a precise, quantitative assay is
      required. It is unclear whether the detection of IgM or low affinity antibodies
      has a role here. A combination of anti-dsDNA, C3, C4, CRP, and ESR assays
      provides the most useful clinical information. Anti-ssDNA assays are likely to be
      useful, and are potentially more robust than anti-dsDNA assays, but require more
      validation. Local validation of individual assays and EQA participation is
      essential. Not all assays that apparently measure the same antibody specificities
      have equal clinical relevance, even within a single technology. Insufficient
      international or national reference preparations are currently available for many
      antibody specificities to enable effective standardisation. Quality assurance
      schemes reveal large differences in units reported by different assays for some
      analytes, even when calibrated against an IRP or equivalent reference
      preparation. Serial results can therefore only be compared from the same
      laboratory at present. Most autoantibodies increase during active disease, but
      few prospective data are currently available to justify treatment on the basis of
      rising titres. Further randomised prospective studies are required to examine the
      importance of antibody isotype and affinity in the monitoring of SLE by
      individual assay methods. The most important aspect of the appropriate use of
      laboratory assays is to become familiar with the limitations of the technology
      currently in use in your local laboratory, and to consult with your clinical
      immunologist in cases of doubt, preferably before commencing serological
      screening.

PMID- 10911803
TI  - Immunoflow cytometry and cell block immunohistochemistry in the FNA diagnosis of
      lymphoma: a review of 73 consecutive cases.
AB  - AIMS: To review the results of 73 consecutive fine needle aspirations (FNAs) that
      were collected by a pathologist and analysed by immunoflow cytometry. Material
      for a cell block was also collected from some of these lesions. METHODS: The
      setting was a large general hospital in rural New Zealand. The FNAs were
      performed by a pathologist, or a radiologist for image guided localisations.
      Material for immunoflow cytometry was collected into RPMI and, when required,
      material for a cell block was collected into formalin. RESULTS: Of the 73 samples
      collected by FNA nine were inadequate. Light chain restriction could be
      demonstrated in most FNA samples from B cell lymphomas (28 of 30 adequate
      samples). The exceptions were two cases of T cell rich B cell lymphoma.
      Artefactual light chain restriction was seen occasionally in T cell lymphomas,
      presumably as a result of autoantibodies binding to the cell surfaces. It was
      possible to subtype most (18 of 30 adequate samples) B cell lymphomas as chronic
      lymphocytic leukaemia (CLL), follicle centre cell lymphoma (FCCL), or mantle cell
      lymphoma. The CD4 to CD8 ratio was not usually restricted in T cell lymphomas and
      coexpression of CD4 and CD8 was not usually found. Loss of pan-T cell antigens
      was seen in some T cell lymphomas. Four of the six T cell lymphomas and three of
      the four non-lymphoid malignacies were diagnosed with the aid of cell block
      immunohistochemistry. Only one of the four cases of Hodgkin's lymphoma showed
      Reed-Sternberg cells in the FNA smears. CONCLUSIONS: It is not always possible to
      characterise lymphomas as fully with FNA and immunoflow cytometry as is possible
      with biopsy histology and a full battery of modern investigations. Nevertheless,
      in the setting of a large rural general hospital immunoflow cytometry on FNA
      samples is a highly effective method of diagnosing and typing B cell lymphomas.
      Immunoflow cytometry is of little use for T cell lymphomas or Hodgkin's
      lymphomas. We advocate the use of cell block immunohistochemistry in preference
      to immunoflow cytometry for cases in which the cytological appearance of the
      specimen is overtly malignant but the differential diagnosis includes non
      lymphoid malignancy.

PMID- 10911802
TI  - ALK expression in extranodal anaplastic large cell lymphoma favours systemic
      disease with (primary) nodal involvement and a good prognosis and occurs before
      dissemination.
AB  - AIMS: In anaplastic large cell lymphoma (ALCL), the site of origin has been
      described as an important prognostic factor. Recently, a fusion protein
      containing anaplastic lymphoma kinase (ALK) was described in systemic nodal ALCL,
      and shown to be associated with a good prognosis. The aims of this study were to
      investigate whether the presence of ALK protein differs between ALCL of different
      sites of origin; to determine whether ALK expression occurs before dissemination
      to other sites; and, finally, to investigate whether the site of origin remains a
      prognostic parameter in ALK negative ALCL. METHODS: ALK expression, as detected
      by immunohistochemistry using the monoclonal antibodies ALK1 and ALKc, was
      studied in 85 ALCLs from different sites of origin. In 22 patients, ALK
      expression was studied in multiple biopsies from different sites (including 13
      skin, 16 lymph node, and nine other). Overall survival time was analysed using
      the Kaplan Meier method. RESULTS: ALK expression was found in 20 of 51 systemic
      ALCLs with (primary) nodal involvement. No ALK expression was found in 15 primary
      cutaneous, 14 gastrointestinal, and five nasal ALCLs. Multiple and subsequent
      biopsies of patients showed ALK expression to be identical to that seen in the
      primary diagnostic biopsy. Kaplan Meier survival curves showed that in ALK
      negative ALCLs originating from different sites, primary cutaneous cases are
      associated with an excellent overall survival, whereas the other cases show a
      comparable five years survival of less than 40%. CONCLUSIONS: If present, ALK
      expression favours systemic ALCL with (primary) nodal involvement, and can be
      used in differentiating between extranodal involvement of systemic (nodal) ALCL
      and primary extranodal ALCL. ALK is expressed consistently in multiple biopsies
      of a given patient, indicating that the chromosomal abnormality leading to
      aberrant ALK expression occurs before dissemination to other sites. Finally, in
      ALK negative non-cutaneous ALCLs, different sites of origin show comparable poor
      survival.

PMID- 10911804
TI  - Malignant lymphoma of the urinary bladder: a clinicopathological study of 11
      cases.
AB  - AIM: To report the clinical and histological features and outcome of primary and
      secondary malignant lymphomas of the urinary bladder. METHODS: Eleven cases of
      malignant lymphoma of the urinary bladder were obtained from the registry of
      cases at St Bartholomews and the Royal London Hospitals. The lymphomas were
      classified on the basis of their morphology and immunophenotype, and the clinical
      records were reviewed. RESULTS: There were six primary lymphomas: three
      extranodal marginal zone lymphomas of mucosa associated lymphoid tissue (MALT)
      type and three diffuse large B cell lymphomas. Of the five secondary cases, four
      were diffuse large B cell lymphomas, one secondary to a systemic follicular
      follicle centre lymphoma, and one nodular sclerosis Hodgkins disease. Four
      patients with secondary lymphoma for whom follow up was available had died of
      disease within 13 months of diagnosis. Primary lymphomas followed a more indolent
      course. In one case, there was evidence of transformation from low grade MALT
      type to diffuse large B cell lymphoma. The most common presenting symptom was
      haematuria. Cystoscopic appearances were of solid, sometimes necrotic tumours
      resembling transitional cell carcinoma, and in one case the tumours were
      multiple. These cases represented 0.2% of all bladder neoplasms. CONCLUSIONS:
      Diffuse large B cell lymphoma and MALT-type lymphoma are the most common primary
      malignant lymphomas of the bladder. Lymphoepithelial lesions in MALT-type
      lymphoma involve transitional epithelium, and their presence in high grade
      lymphoma suggests a primary origin owing to transformation of low grade MALT-type
      lymphoma. Primary and secondary diffuse large B cell lymphomas of the bladder are
      histologically similar, but the prognosis of the former is favourable.

PMID- 10911805
TI  - Evaluation of argyrophilic nucleolar organiser regions (AgNORs) in multiple
      myeloma.
AB  - AIM: To investigate the prognostic value of argyrophylic nucleolar organiser
      regions (AgNORs) in multiple myeloma. METHODS: Bone marrow aspirates from 55
      newly diagnosed patients with multiple myeloma were stained with the one step
      AgNO3 technique. The mean number of AgNORs in each plasma cell nucleus (AgNOR
      count) was tested for a possible correlation with other clinical and laboratory
      variables at presentation (clinical stage, substage, heavy and light chain
      isotype, haemoglobin concentration, platelet count, marrow infiltration rate,
      degree of skeletal lesions, M protein concentration, plasma cell morphology, and
      serum concentrations of calcium, albumin, lactate dehydrogenase, C reactive
      protein, and beta 2 microglobulin) and with outcome (response to first line
      treatment, first remission duration, and overall survival). RESULTS: A
      significant association between mean (SD) AgNOR count was found only for clinical
      stage (stage I, 3.09 (1.19); stage II, 3.80 (1.53); stage III, 5.28 (1.79); p <
      0.005) and, from all stage determinants, only for M protein concentration (high,
      5.92 (1.80); low, 4.01 (1.92); p < 0.001). There was a linear relation between
      AgNOR count and serum M protein concentration for patients with both IgG (r =
      0.450; p < 0.01) and IgA (r = 0.768; p < 0.002) producing multiple myeloma.
      CONCLUSIONS: Unlike previous investigations, no clear prognostic value for the
      AgNOR count was found in multiple myeloma. Instead, the results indicate that the
      AgNOR count might be an index for M protein synthesis rate. This is consistent
      with other findings in tissues with low proliferative potential and high protein
      synthetic activity, and calls for a cautious interpretation of AgNORs in
      malignancies with similar features.

PMID- 10911806
TI  - Presence of mitochondrial tRNA(Leu(UUR)) A to G 3243 mutation in DNA extracted
      from serum and plasma of patients with type 2 diabetes mellitus.
AB  - AIMS/BACKGROUND: An A to G substitution at base pair 3243 in the mitochondrial
      tRNA(Leu(UUR)) gene (mt3243) is commonly associated with maternally inherited
      diabetes and deafness, and other diseases. It is possible that cell free
      mitochondrial DNA exists in serum and plasma from these patients, and these
      samples might be a source of material for the detection of such mutations.
      METHODS: Sixteen patients with type 2 diabetes mellitus and 25 healthy subjects
      were tested for the 3243 mutation by polymerase chain reaction restriction
      fragment length polymorphism (PCR-RFLP) analysis. Plasma and serum from the 41
      subjects were tested blind, without knowledge of the final diagnosis. RESULTS:
      PCR amplification of the mtRNA(Leu(UUR)) region in mitochondrial DNA (mtDNA) in
      serum samples revealed the presence of mtDNA in all samples. After ApaI digestion
      of the amplified DNA fragments, mt3243 was detected in the serum and plasma
      samples of the seven patients with diabetes who had previously been found to have
      this mutation in their leucocyte DNA. None of the serum/plasma samples from the
      healthy subjects or those patients negative for mt3243 in their leucocytes had
      this mutation (p < 0.001). In addition, the degree of heteroplasmy of mt3243
      appeared to be higher in serum and plasma samples than in leucocytes among mt3243
      carriers (p < 0.05). CONCLUSIONS: Therefore, mtDNA and associated mutations are
      present and detectable in serum and plasma. Plasma and serum might be alternative
      sources for the molecular diagnosis of mt3243 associated diabetes mellitus, as
      well as other mitochondrial mediated diseases.

PMID- 10911807
TI  - Photodynamic treatment of pooled coumarin plasma for external quality assessment
      of the prothrombin time.
AB  - AIMS: To determine the conditions of photodynamic inactivation of vesicular
      stomatitis virus (VSV) added to pooled coumarin plasma and the effects of the
      photodynamic treatment on the prothrombin times and international normalised
      ratio (INR) in a Netherlands national external quality assessment scheme.
      METHODS: Pooled coumarin plasma samples were illuminated with visible light in
      the presence of 1 microM methylene blue. Inactivation conditions for VSV in
      pooled coumarin plasma were determined using an end point dilution assay. Plasma
      illuminated for 20 minutes was mixed with red blood cells and mailed to
      participants of the Netherlands external quality assessment (EQA) scheme.
      Prothrombin times and INRs were determined with various thromboplastin reagents.
      RESULTS: Photodynamic treatment using 1 microM methylene blue and 700 W/m2 caused
      4.7 log inactivation of VSV in pooled coumarin plasma. Fibrinogen and coagulation
      factors II, V, VII, and X were decreased slightly by the treatment. These
      conditions caused prolongation of the prothrombin time in EQA surveys. The
      magnitude of the effect was different for various thromboplastin reagents. The
      increase of the INR was negligible when measured with the Thrombotest reagent.
      With other reagents, an approximately 5-16% increase of the INR was observed.
      Interlaboratory variation of the INR was not affected by photodynamic treatment.
      CONCLUSIONS: Photodynamic treatment of pooled coumarin plasma is very effective
      for the inactivation of some enveloped viruses such as VSV, but has only a
      limited effect on the prothrombin time and INR. Photodynamic treatment can be
      used to improve the viral safety of coumarin plasma for EQA of the prothrombin
      time and INR.

PMID- 10911808
TI  - Benchmarking general practice use of pathology services: a model for monitoring
      change.
AB  - AIMS: To identify a model to assess general practitioner use of pathology
      services that could be applied to assess specific interventions designed to
      promote best practice. METHODS: A database containing standardised requesting
      data for 22 general practices was constructed. The database contained 28 tests
      covering 95% of general practitioner activity, distributed across pathology, and
      it was evaluated during two sequential six month periods. A comparison of ranks
      of requesting activity between different time periods was undertaken by
      calculating Pearson rank correlation coefficients. Requesting numbers were also
      adjusted for patients' age and sex distributions within the 22 practices for a
      sample of three high volume tests. The effects of distributing requesting
      guidelines and details of requesting activity were assessed during two sequential
      three month periods. RESULTS: Requesting activity was extremely stable during the
      two baseline periods for most test (r > 0.80 for 20 of the 28 tests). Several
      less discriminatory tests were identified. Age and sex adjustment had minimal
      impact on the ranks of requesting activity. Requesting activity during the two
      three month periods after distributing guidelines and comparative details of
      individual requesting activity showed little change (overall correlation
      coefficient, 0.844 between baseline and intervention periods). CONCLUSIONS:
      Ranking general practitioners requesting activity adjusted for practice list size
      provides a reproducible means of measuring requesting activity for most pathology
      tests performed in general practice. Activity was not influenced by age or sex of
      patients on the practice list. Distributing requesting guidelines and individual
      requesting activity on their own do not have any measurable impact on requesting
      activity. More innovative (possibly multiple) interventions might be required to
      influence general practitioner requesting practice.

PMID- 10911809
TI  - Exercise induced mobilisation of the marginated granulocyte pool in the
      investigation of ethnic neutropenia.
AB  - This study was designed to determine whether ethnic neutropenia is caused by an
      increased proportion of neutrophils being present in the marginated granulocyte
      pool. Thirty two healthy volunteers, half of whom were African or Afro-Caribbean
      and half of whom were white, exercised vigorously for 10 minutes on a step
      machine to mobilise granulocytes from the marginated granulocyte pool into the
      circulating granulocyte pool. The amount of work performed and the pulse rate
      response of the two ethnic groups were compared to determine whether the exercise
      carried out was comparable. A full blood count and an automated differential
      count were performed before and after the exercise. The haemoglobin
      concentration, platelet count, and absolute counts of total leucocytes and
      leucocyte subsets before and after exercise were compared in each individual and
      the values in the two ethnic groups both before and after exercise were compared.
      The absolute increase in neutrophils in the two ethnic groups was compared. The
      African/Afro-Caribbean group was found to have a reduced rather than enhanced
      ability to mobilise neutrophils from the marginated granulocyte pool. Therefore,
      increased margination of neutrophils is unlikely to be the cause of ethnic
      neutropenia.

PMID- 10911810
TI  - Re: Intra-alveolar haemorrhage in sudden infant death syndrome: a cause for
      concern?

PMID- 10911811
TI  - Re: Gynaecological effects of tamoxifen.

PMID- 10911812
TI  - Understanding non-compliance with treatment in adults with cystic fibrosis.

PMID- 10911813
TI  - The compliance conundrum in cystic fibrosis.

PMID- 10911814
TI  - The role of vitamins in cystic fibrosis.

PMID- 10911815
TI  - Holidays and cystic fibrosis.

PMID- 10911816
TI  - Physiotherapy in cystic fibrosis.

PMID- 10911817
TI  - Bronchodilators in cystic fibrosis.

PMID- 10911819
TI  - Goodbye to presenteeism.

PMID- 10911818
TI  - Infection control in cystic fibrosis: methicillin-resistant Staphylococcus
      aureus, Pseudomonas aeruginosa and the Burkholderia cepacia complex.

PMID- 10911820
TI  - Nut allergy in children: investigation and management.

PMID- 10911821
TI  - Air pollution--better or worse?

PMID- 10911822
TI  - Palliative care in India.

PMID- 10911824
TI  - Practice guidelines and other support for clinical innovation.

PMID- 10911823
TI  - How relevant are animal models to human ageing?

PMID- 10911825
TI  - Randomized controlled trial of nettle sting for treatment of base-of-thumb pain.
AB  - There are numerous published references to use of nettle sting for arthritis pain
      but no randomized controlled trials have been reported. We conducted a randomized
      controlled double-blind crossover study in 27 patients with osteoarthritic pain
      at the base of the thumb or index finger. Patients applied stinging nettle leaf
      (Urtica dioica) daily for one week to the painful area. The effect of this
      treatment was compared with that of placebo, white deadnettle leaf (Lamium
      album), for one week after a five-week washout period. Observations of pain and
      disability were recorded for the twelve weeks of the study. After one week's
      treatment with nettle sting, score reductions on both visual analogue scale
      (pain) and health assessment questionnaire (disability) were significantly
      greater than with placebo (P = 0.026 and P = 0.0027).

PMID- 10911826
TI  - Diagnosis of psychiatric disorder in clinical evaluation of chronic fatigue
      syndrome.
AB  - The overlap of symptoms in chronic fatigue syndrome (CFS) and psychiatric
      disorders such as depression can complicate diagnosis. Patients often complain
      that they are wrongly given a psychiatric label. We compared psychiatric
      diagnoses made by general practitioners and hospital doctors with diagnoses
      established according to research diagnostic criteria. 68 CFS patients referred
      to a hospital fatigue clinic were assessed, and psychiatric diagnoses were
      established by use of a standardized interview schedule designed to provide
      current and lifetime diagnoses. These were compared with psychiatric diagnoses
      previously given to patients. Of the 31 patients who had previously received a
      psychiatric diagnosis 21 (68%) had been misdiagnosed: in most cases there was no
      evidence of any past or current psychiatric disorder. Of the 37 patients who had
      not previously received a psychiatric diagnosis 13 (35%) had a treatable
      psychiatric disorder in addition to CFS. These findings highlight the
      difficulties of routine clinical evaluation of psychiatric disorder in CFS
      patients. We advise doctors to focus on subtle features that discriminate between
      disorders and to use a brief screening instrument such as the Hospital Anxiety
      and Depression Scale.

PMID- 10911827
TI  - A multiple-sclerosis-like syndrome associated with glue-sniffing.

PMID- 10911828
TI  - Alimentary hyperglycaemia mistaken for diabetes mellitus.

PMID- 10911829
TI  - Acute myocardial infarction without raised creatine kinase activity.

PMID- 10911830
TI  - Epstein-Barr virus infection mimicking extrahepatic biliary obstruction.

PMID- 10911831
TI  - Salmonella meningitis and a green iguana.

PMID- 10911832
TI  - Angel's trumpet and the eye.

PMID- 10911833
TI  - Seven questions about paediatric research.

PMID- 10911834
TI  - Treatments for bubonic plague: reports from seventeenth century British
      epidemics.

PMID- 10911835
TI  - Insulin coma therapy for schizophrenia.

PMID- 10911836
TI  - Surgical correction of refractive error.

PMID- 10911837
TI  - Female beauty.

PMID- 10911838
TI  - Pain management in herpes zoster ophthalmicus.

PMID- 10911839
TI  - Venous pulsation in the orbit.

PMID- 10911840
TI  - The emperor with the shaking head.

PMID- 10911841
TI  - Malaria with a positive 'monospot' test.

PMID- 10911842
TI  - Ancient records of birth defects.

PMID- 10911843
TI  - Pulled elbow.

PMID- 10911844
TI  - The most pressing issue?

PMID- 10911845
TI  - Chronic fatigue syndrome in mother and child.

PMID- 10911846
TI  - Bias in peer review.

PMID- 10911847
TI  - An introduction to sexually transmitted infections: the 1976 volume of the
      British Journal of Venereal Diseases.

PMID- 10911848
TI  - Infectivity tests in syphilis. 1969.

PMID- 10911849
TI  - The prevention of syringe-transmitted hepatitis. 1946.

PMID- 10911850
TI  - Cortisone in the treatment of syphilitic eye disease. 1953.

PMID- 10911851
TI  - Ocular syndromes of TRIC virus infection and their possible genital significance.
      1964.

PMID- 10911852
TI  - My choice: Ocular syndromes of TRIC virus infection and their possible genital
      significance.

PMID- 10911853
TI  - Medical professional secrecy with special reference to venereal diseases. 1967.

PMID- 10911854
TI  - Natural history of genital warts. 1971.

PMID- 10911855
TI  - Chlamydial infection. Isolation of Chlamydia from patients with non-specific
      genital infection. 1972.

PMID- 10911856
TI  - 27 years of uninterrupted contact tracing the "Tyneside scheme". 1972.

PMID- 10911857
TI  - Chlamydial infection. Incidence in 'non-specific' urethritis. 1972.

PMID- 10911858
TI  - The first Harrison Lecture 1974. The life and times of Colonel L W Harrison.
      1974.

PMID- 10911859
TI  - Changes in the incidence of acute gonococcal and nongonococcal salpingitis. 1978.

PMID- 10911860
TI  - Survival of treponemes after treatment: comments, clinical conclusions, and
      recommendations. 1986.

PMID- 10911861
TI  - Sexual behaviour in women attending a genitourinary medicine clinic. 1988.

PMID- 10911862
TI  - Teenagers and the risks of sexually transmitted diseases: a need for the
      provision of balanced information. 1992.

PMID- 10911863
TI  - The parahippocampal region. Implications for neurological and psychiatric
      diseases. Introduction.

PMID- 10911864
TI  - Anatomical organization of the parahippocampal-hippocampal network.
AB  - The anatomical organization of the parahippocampal-hippocampal network indicates
      that it consists of different parallel circuits. Considering the topographical
      distribution of sensory cortical inputs, the hypothesis is that the major
      parallel circuits carry functionally different information. These functionally
      different parallel routes reach different portions of the hippocampal network
      along the longitudinal axis of all fields as well as along the perpendicularly
      oriented transverse axis of CA1 and the subiculum. In the remaining fields of the
      hippocampal formation, that is, the dentate gyrus and CA2/CA3, separation along
      the transverse axis is not present. By contrast, here the functionally different
      pathways converge onto the same neuronal population. The entorhinal cortex holds
      a pivotal position among the cortices that make up the parahippocampal region. By
      way of the networks of the superficial and deep layers, it mediates,
      respectively, the input and output streams of the hippocampal formation.
      Moreover, the intrinsic entorhinal network, particularly the interconnections
      between the deep and superficial layers, may mediate the comparison of
      hippocampal input and output signals. As such, the entorhinal cortex may form
      part of a novelty detection network. In addition, the organization of the
      entorhinal-hippocampal network may facilitate the holding of information.
      Finally, the terminal organization of the presubicular input to the medial
      entorhinal cortex indicates that the interactions between the deep and
      superficial entorhinal layers may be influenced by this input.

PMID- 10911865
TI  - The parahippocampal region: corticocortical connectivity.
AB  - The parahippocampal region, as defined in this review, comprises the cortical
      regions that surround the rodent hippocampus including the perirhinal,
      postrhinal, and entorhinal cortices. The comparable regions in the primate brain
      are the perirhinal, parahippocampal, and entorhinal cortices. The perirhinal and
      postrhinal/parahippocampal cortices provide the major polysensory input to the
      hippocampus through their entorhinal connections and are the recipients of
      differing combinations of sensory information. The differences in the perirhinal
      and postrhinal cortical afferentation have important functional implications, in
      part, because these two regions project with different terminal patterns to the
      entorhinal cortex. The perirhinal cortex projects preferentially to the lateral
      entorhinal area (LEA), and the postrhinal cortex projects preferentially to the
      medial entorhinal area (MEA) and the caudal portion of LEA. Although the
      perirhinal and postrhinal cortices provide the major cortical input to the
      entorhinal cortex, the entorhinal cortex itself receives some direct cortical
      input. An examination of the cortical afferentation of the entorhinal cortex
      reveals an interesting principle of connectivity among these regions; the
      composition of the direct neocortical input to the LEA is more similar to that of
      the perirhinal cortex, and the composition of the direct neocortical input to the
      MEA is more similar to that of the postrhinal cortex. Thus, polymodal
      associational input to the LEA and the MEA exhibits some segregation and is
      organized in parallel. The organization of intrinsic connections for each of the
      parahippocampal regions also contributes to the segregation of information into
      parallel pathways.

PMID- 10911866
TI  - Development of the entorhino-hippocampal projection: guidance by Cajal-Retzius
      cell axons.
AB  - The entorhinal cortex gives rise to a massive projection to the hippocampus and
      fascia dentata. In the rat, this projection forms early in development with first
      entorhinal axons reaching the hippocampus around embryonic day (E) 17. From the
      very beginning, the entorhinal axons recognize their appropriate termination
      zones in the hippocampus proper and fascia dentata, i.e., stratum lacunosum
      moleculare and the outer molecular layer of the dentate. This is remarkable,
      because at the time of entorhinal fiber ingrowth, the definitive target cells of
      entorhinal axons, pyramidal cells and granule cells, are not yet fully developed,
      and the majority of their distal dendritic tips have not yet reached these
      layers. This raises the question as to the cellular and molecular signals guiding
      the entorhinal axons to and keeping them in their target layers. Here we
      hypothesize that early generated Cajal-Retzius (CR) cells located in stratum
      lacunosum-moleculare and the outer molecular layer of the dentate, and in
      particular their axons projecting to the entorhinal cortex, provide a template
      that is used by the entorhinal axons to find their target layers in the
      hippocampus.

PMID- 10911867
TI  - Physiology of the entorhinal and perirhinal projections to the hippocampus
      studied by current source density analysis.
AB  - Evoked field potentials and current-source-density analysis were used to study
      the olfactory, entorhinal, and perirhinal projections to the hippocampus. In
      urethane-anesthetized rats, various structures were electrically stimulated, and
      evoked potentials were mapped using glass micropipettes or multichannel silicon
      probes. Stimulation of the olfactory bulb, lateral olfactory tract, piriform
      cortex, amygdala-entorhinal transition, lateral entorhinal cortex, or lateral
      perforant path (LPP) evoked an outer molecular layer sink (inferred distal
      dendritic excitation) in the dentate gyrus, with progressively decreasing onset
      latency. Medial perforant path (MPP) stimulation evoked a middle molecular layer
      sink (mid-dendritic excitation) in the dentate gyrus. LPP and MPP were also
      inferred to monosynaptically excite the distal dendrites of CA3, often resulting
      in a population spike in CA3. CA3 spiking, in turn, was often followed by
      excitation at the inner molecular layer of the dentate gyrus. LPP and MPP evoked
      distal dendritic sinks but no population spikes in CA1. Stimulation of the
      perirhinal cortex activated a sink in the subiculum/CA1 border without activating
      the dentate gyrus. In addition, reverberatory activity through a hippocampal
      entorhinal-hippocampal pathway may be activated by MPP or CA3 stimulation. It is
      suggested that the parallel projections of the entorhinal and perirhinal inputs
      to the distal dendrites of hippocampal principal neurons enhance local and
      distributed processing as characterized by CA3 to dentate gyrus feedback, and
      hippocampal-entorhinal reverberation.

PMID- 10911868
TI  - Molecular effects of the psychotropic NMDA receptor antagonist MK-801 in the rat
      entorhinal cortex: increases in AP-1 DNA binding activity and expression of Fos
      and Jun family members.
AB  - Noncompetitive NMDA receptor antagonists such as phencyclidine and MK-801 produce
      psychotropic symptoms that closely resemble schizophrenic psychosis and induce
      the expression of immediate early genes in limbic cortical areas. We are
      concentrating on analyzing molecular and physiological effects that these drugs
      produce in the entorhinal cortex and on the potential connection between these
      effects and the psychotic symptoms. We show here that MK-801 increases the DNA
      binding activity of the activator protein-1 (AP-1) complex in the entorhinal
      cortex. We also observed increased expression of mRNAs for Fos and Jun
      transcription factor family members c-Fos, FosB, Fra-2, and JunB, as well as Fos
      family proteins in the entorhinal cortex after MK-801 administration. This
      suggests that the activated AP-1 complex consists of these transcription factors.
      Genes regulated by the AP-1 complex in the entorhinal cortex might be involved in
      the pathophysiology of psychotic behavior and are potential targets for new
      antipsychotic drugs.

PMID- 10911869
TI  - Two-phase computational model training long-term memories in the entorhinal
      hippocampal region.
AB  - The computational model described here is driven by the hypothesis that a major
      function of the entorhinal cortex (EC)-hippocampal system is to alter synaptic
      connections in the neocortex. It is based on the following postulates: (1) The EC
      compares the difference between neocortical representations (primary input) and
      feedback information conveyed by the hippocampus (the "reconstructed input"). The
      difference between the primary input and the reconstructed input (termed "error")
      initiates plastic changes in the hippocampal networks (error compensation). (2)
      Comparison of the primary input and reconstructed input requires that these
      representations are available simultaneously in the EC network. We suggest that
      compensation of time delays is achieved by predictive structures, such as the CA3
      recurrent network and EC-CA1 connections. (3) Alteration of intrahippocampal
      connections gives rise to a new hippocampal output. The hippocampus generates
      separated (independent) outputs, which, in turn, train long-term memory traces in
      the EC (independent components, IC). The ICs of the long-term memory trace are
      generated in a two-step manner, the operations of which we attribute to the
      activities of the CA3 (whitening) and CA1 (separation) fields. (4) The different
      hippocampal fields can perform both nonlinear and linear operations, albeit at
      different times (theta and sharp phases). We suggest that long-term memory is
      represented in a distributed and hierarchical reconstruction network, which is
      under the supervision of the hippocampal output. Several of these model
      predictions can be tested experimentally.

PMID- 10911870
TI  - Properties of entorhinal cortex projection cells to the hippocampal formation.
AB  - There are multiple connections from the entorhinal cortex (EC) to the hippocampus
      that carry the information from the EC to the hippocampus. Layer II cells of the
      medial EC innervating the dentate gyrus (DG)-molecular layer possess K(+)-outward
      currents and inward rectifier currents that are potentially modulated by changes
      in intracellular second messengers. Layer II cells responded to synaptic
      stimulation with a rather flat input-output curve, and much stronger stimuli are
      required to generate action potentials in these neurons than in EC layer III
      cells. During repetitive stimulation at frequencies of 10 Hz and more, EC layer
      II cells respond with increased likelihood to generate action potentials. Two
      different NMDA conductances can be demonstrated in these neurons. A slow, less
      Mg, less voltage-dependent component is responsible for the transient
      depolarization between the fast and slow IPSP. A second group of neurons also
      projects to the DG. These are either pyramidal or nonpyramidal cells in the deep
      layers of the EC. At least part of these neurons also possess rhythmogenic
      properties. In contrast to layer II cells, layer III neurons have a steep input
      output curve and show during repetitive synaptic activation a tendency to
      repolarize and to display long-lasting inhibitions dependent on GABAB-, atropine
      , and naloxone-sensitive components. As a consequence, they are readily activated
      during low frequency stimulation, but project only a few action potentials to
      area CA1 initially during higher (more than 10 Hz) frequency synaptic
      stimulation.

PMID- 10911871
TI  - Oscillatory activity in entorhinal neurons and circuits. Mechanisms and function.
AB  - Layers II and V of the entorhinal cortex (EC) occupy a privileged anatomical
      position in the temporal lobe memory system that allows them to gate the main
      flow of information in and out of the hippocampus, respectively. In vivo studies
      have shown that layer II of the EC is a robust generator of theta as well as
      gamma activity. Theta may also be present in layer V, but the layer V network is
      particularly prone to genesis of short-lasting high-frequency oscillations
      ("ripples"). Interestingly, in vitro studies have shown that EC layers II and V,
      but not layer III, have the potential to act as independent pacemakers of
      population oscillatory activity. Moreover, it has also been shown that subgroups
      of principal neurons both within layers II and V, but not layer III, are endowed
      with autorhythmic properties. These are characterized by subthreshold
      oscillations where the depolarizing phase is driven by the activation of
      "persistent" Na+ channels. We propose that the oscillatory properties of layer II
      and V neurons and local circuits are responsible for setting up the proper
      temporal dynamics for the coordination of the multiple sensory inputs that
      converge onto EC and thus help to generate sensory representations and memory
      encoding.

PMID- 10911872
TI  - Differential information processing by hippocampal and subicular neurons.
AB  - It has been known for some years that hippocampal neurons are critically involved
      in processing of information necessary for encoding memories. What is less
      understood is the role of the subiculum in this process. We describe here
      differential response characteristics of subicular and hippocampal neurons in
      rats during execution of a delayed-nonmatch-to-sample short-term memory task.
      Subicular neurons, unlike hippocampal neurons, fire primarily in the delay
      interval of the task and appear to provide a temporal linkage between events
      encoded in hippocampus during the sample and nonmatch phases. Indeed, a large
      proportion of subicular neurons fire robustly for the entire duration of the
      delay only. Further analyses using electrical activation methods indicate that
      subicular neurons that receive short latency inputs from the anterior thalamus
      and do not project to cingulate cortex are the most responsive to stimuli with
      behavioral significance.

PMID- 10911873
TI  - The parahippocampal region and object identification.
AB  - The hippocampus has long been thought to be critical for memory, including memory
      for objects. However, recent neuropsychological studies in nonhuman primates have
      indicated that other regions within the medial temporal lobe, specifically,
      structures in the parahippocampal region, are primarily responsible for object
      recognition and object identification. This article reviews the behavioral
      effects of removal of structures within the parahippocampal region in monkeys,
      and cites relevant work in rodents as well. It is argued that the perirhinal
      cortex, in particular, contributes to object identification in at least two ways:
      (i) by serving as the final stage in the ventral visual cortical pathway that
      represents stimulus features, and (ii) by operating as part of a network for
      associating together sensory inputs within and across sensory modalities.

PMID- 10911874
TI  - The neurophysiology of memory.
AB  - How do the structures of the medial temporal lobe contribute to memory? To
      address this question, we examine the neurophysiological correlates of both
      recognition and associative memory in the medial temporal lobe of humans,
      monkeys, and rats. These cross-species comparisons show that the patterns of
      mnemonic activity observed throughout the medial temporal lobe are largely
      conserved across species. Moreover, these findings show that neurons in each of
      the medial temporal lobe areas can perform both similar as well as distinctive
      mnemonic functions. In some cases, similar patterns of mnemonic activity are
      observed across all structures of the medial temporal lobe. In the majority of
      cases, however, the hippocampal formation and surrounding cortex signal mnemonic
      information in distinct, but complementary ways.

PMID- 10911875
TI  - Involvement of non-neuronal cells in entorhinal-hippocampal reorganization
      following lesions.
AB  - Entorhinal lesion leads to anterograde degeneration of perforant path fibers in
      their main hippocampal termination zones. Subsequently, remaining fibers sprout
      and form new synapses on the denervated dendrites. This degeneration and
      reorganization is accompanied by sequential changes in glial morphology and
      function. Within a few hours following the lesion, amoeboid microglia migrate
      into the zone of denervation. Some hours later, signs of activation can be seen
      on astrocytes in the zone of denervation, where both cell types proliferate and
      remain in an activated state for more than two weeks. These activated glial cells
      might be involved in lesion-induced plasticity in at least two ways: (1) by
      releasing cytokines and growth factors which regulate layer-specific sprouting
      and (2) by phagocytosis of axonal debris, because myelin sheaths act as obstacles
      for sprouting fibers in the central nervous system. Whereas direct evidence for
      the former is still missing, the latter was investigated using phagocytosis
      dependent labeling techniques. Both microglial cells and astrocytes incorporate
      axonal debris. Phagocytosing microglial cells develop the immune phenotype of
      antigen-presenting cells, whereas astrocytes strongly express FasL (CD95L), which
      induces apoptosis of activated lymphocytes. Thus, the interaction of glial cells
      with immune cells might be another, previously underestimated, aspect of
      reorganization following entorhinal lesion.

PMID- 10911876
TI  - Reorganization of the rat fascia dentata after a unilateral entorhinal cortex
      lesion. Role of the extracellular matrix.
AB  - Entorhinal cortex lesion (ECL) partially denervates the fascia dentata of the
      hippocampus. This is said to induce the sprouting of intact fibers from
      neighboring layers that invade the zone of the degenerating axons. However,
      recent studies using anterograde tracing failed to demonstrate sprouting across
      laminar boundaries. Sprouting does occur, but it mainly involves unlesioned fiber
      systems terminating within the layer of fiber degeneration. It is now of interest
      to identify the cues that could underlie this layer-specific sprouting response.
      Since extracellular matrix (ECM) molecules delineate boundaries of axonal growth
      during development, it was tested whether these molecules play a similar role
      during the sprouting process following ECL. After ECL, reactive astrocytes
      rapidly synthesize and secrete growth-inhibiting ECM molecules, such as tenascin
      C and the chondroitin sulfate proteoglycan neurocan, into the ECM of the outer
      molecular layer. These molecules form a sharp border against the nondenervated
      inner molecular layer. This pattern of ECM molecule expression may contribute to
      the layer-specific sprouting response of surviving afferents after ECL: axons
      trying to grow into the denervated outer molecular layer, for example, from the
      inner molecular layer, would be deflected by a growth-inhibiting ECM barrier.

PMID- 10911877
TI  - Pathological changes in the parahippocampal region in select non-Alzheimer's
      dementias.
AB  - The transentorhinal and entorhinal regions of the human brain extend over the
      ambient gyrus and anterior portions of the parahippocampal gyrus. They are
      important components of the limbic loop which receives its major afferents from
      the neocortical sensory association areas and generates powerful efferent
      projections both directly and via intermediary relay stations to the prefrontal
      cortex. The bilateral structural preservation of limbic loop components is a
      prerequisite for the maintenance of intact memory functions. In progressive
      neurodegenerative diseases, such as Alzheimer's disease, argyrophilic grain
      disease, Pick's disease, idiopathic Parkinson syndrome, and Huntington's disease,
      the transentorhinal and entorhinal regions are particularly susceptible to severe
      pathological changes. The transentorhinal region typically registers the initial
      alterations and becomes the most severely involved. From this transitional region
      of the mesocortex, the alterations usually invade with decreasing severity both
      the entorhinal region and temporal proneocortex. Each type of lesion that
      develops in the above-mentioned neurodegenerative disorders hampers or even
      interrupts data-transport from the sensory neocortex to the prefrontal neocortex,
      thereby contributing to the insidious development of progressive changes in
      personality, cognitive decline, and, ultimately, dementia.

PMID- 10911878
TI  - From healthy aging to early Alzheimer's disease: in vivo detection of entorhinal
      cortex atrophy.
AB  - Using quantitative structural MRI protocols, we examined the effects of age on
      alterations in entorhinal cortex (EC) volume. The left EC was found to be smaller
      than the right in both young and healthy aged subjects. More importantly, the
      right EC, but not the left, was significantly smaller in elderly participants
      compared to young controls. In an attempt to determine the earliest sites of
      involvement in mild and incipient Alzheimer's disease (AD), we compared
      entorhinal and hippocampal volume in (1) healthy elderly controls, (2) patients
      with very mild AD, and (3) elderly patients who were evaluated for cognitive
      complaints, but did not meet criteria for dementia. Both patient groups differed
      from controls in EC volume, but not from each other. In contrast, the two patient
      groups differed in hippocampal volume from controls, as well as from each other,
      with the mild AD cases showing the greatest atrophy. These results suggest that
      degeneration of the EC and hippocampal formation occurs before the onset of overt
      dementia. In fact, follow-up clinical evaluations available on 23 of 28
      nondemented patients indicated that 12 of 23 had converted to AD. Converters
      could be best differentiated from nonconverters on the basis of entorhinal
      volume.

PMID- 10911879
TI  - The parahippocampal gyrus in Alzheimer's disease. Clinical and preclinical
      neuroanatomical correlates.
AB  - The human parahippocampal gyrus forms a large part of the limbic lobe along the
      ventromedial part of the temporal cortical mantle. It is a variable and
      complicated cortex in terms of structure, and the latter is aggravated further by
      interfaces with the anterior insula anteriorly and the cingulate gyrus and
      occipital lobe posteriorly. Additional complications relate to its lateral border
      with the temporal cortex and especially the sulcal configurations that define
      this junction. The rhinal sulcus, which separates parahippocampal and temporal
      cortices in other species, including the anthropoid apes, is either lacking or
      rudimentary in the human brain. Thus, defining this junction requires
      cytoarchitectural examination and precludes the use of mere inspection of sulcal
      existing patterns. The cortical areas that form the parahippocampal gyrus are
      vulnerable to pathological changes in Alzheimer's disease (AD), and its
      entorhinal and perirhinal subdivisions are both the most heavily damaged cortical
      areas and the focus for disease onset. The neurons that acquire neurofibrillary
      tangles (NFTs) occupy the junction of the isocortical mantle with the limbic
      cortical mantle, but share, or partially share, a vulnerability phenotype with
      large neurons in both domains. The differential expression of this phenotype
      across time creates the false impression of NFT spread in cross-sectional
      comparisons of AD brains. The questions of what this phenotype is and why it is
      expressed first in the perirhinal and entorhinal cortices of the parahippocampal
      gyrus are the central molecular biological/neuroanatomical questions in
      understanding the etiology of AD.

PMID- 10911880
TI  - Cellular and molecular neuropathology of the parahippocampal region in
      schizophrenia.
AB  - The entorhinal cortex, subiculum, and hippocampus have been regions of great
      interest in both clinical and neuropathological investigations of schizophrenia.
      Postmortem studies have identified numerous abnormalities, although many remain
      controversial or unconfirmed. Among the cellular and molecular neuropathological
      findings are (1) abnormal cytoarchitecture of the entorhinal cortex characterized
      by poorly formed layer II neuron clusters and laminar disorganization; (2) normal
      neuron density but smaller neuron size in the superficial lamina of the
      entorhinal cortex and subiculum; (3) abnormal expression of the microtubule
      associated protein MAP2 in the entorhinal cortex and subiculum; (4) aberrant
      glutamatergic and catecholaminergic innervation of the entorhinal cortex; (5)
      abnormal mRNA expression of various transcription factors, ion channels, and
      neurosecretory pathway-related proteins in entorhinal stellate neurons; and (6)
      an absence of any neurodegeneration. Altogether, these findings suggest that
      aberrant neurodevelopmental processes play a key role in the pathobiology of
      schizophrenia and provide a neuroanatomic basis for understanding many of the
      clinical and neuropsychological abnormalities in the disorder.

PMID- 10911882
TI  - Epileptogenesis in the parahippocampal region. Parallels with the dentate gyrus.
AB  - Limbic seizures have often been attributed to pathology in the hippocampus, such
      as the well described condition termed Ammon's Horn sclerosis, in which many of
      the hippocampal principal cells have degenerated. However, several studies in
      both the clinical and basic literature indicate that the parahippocampal region
      may also play an important role. This region sustains a characteristic pattern of
      damage in most animal models of epilepsy that is similar to that identified in
      humans with intractable temporal lobe epilepsy. Perhaps the most striking aspect
      of parahippocampal pathology is the marked loss of neurons in layer III of the
      entorhinal cortex. The similarity of cell loss in layer III and cell loss in the
      hilus of the dentate gyrus is compared, as is the characteristic resistance of
      layer II neurons and dentate granule cells. Cellular electrophysiological results
      are used as a basis for the hypothesis that synaptic inhibition plays a role in
      the relative vulnerability of these neurons. Studies of neurogenesis in both
      areas is also discussed. It is proposed that this may be an additional factor
      that influences vulnerability in these areas.

PMID- 10911881
TI  - Amygdalo-entorhinal inputs to the hippocampal formation in relation to
      schizophrenia.
AB  - This chapter reviews recent postmortem studies of schizophrenic brain and
      discusses the potential role of the amygdala in the induction of hippocampal
      abnormalities in this disorder. Based on available evidence, sectors CA4, CA3,
      and CA2, but not CA1, show preferential changes in schizophrenic subjects,
      although the most pronounced changes have been found in CA3 and CA2. It seems
      likely that the amygdala would contribute in some way to the induction of
      abnormalities along the trisynaptic pathway via its direct input to sectors CA3
      and CA2, as well as an indirect one that involves the entorhinal cortex and its
      perforant path projection to the area dentata. The postmortem findings reported
      to date have been integrated into a working model in which decreases of
      inhibitory GABAergic modulation are invoked to explain the observation from a
      recent PET scan study (Heckers et al., 1999) that baseline metabolic activity in
      the hippocampus of schizophrenics is increased. In addition, however, the
      apparent inability of schizophrenics to increase metabolic activity in the
      hippocampus when challenged with a memory retrieval task may reflect a
      disturbance of disinhibitory modulation postulated herein to occur in sector CA3,
      a key relay point along the trisynaptic pathway. Overall, it seems plausible that
      an increase of excitatory activity entering the hippocampus from the basolateral
      complex via both direct and indirect pathways may make a significant contribution
      to the pathophysiology of schizophrenia.

PMID- 10911883
TI  - Neurons in layer III of the entorhinal cortex. A role in epileptogenesis and
      epilepsy?
AB  - A preferential lesion of neurons in layer III of the entorhinal cortex (EC) is
      often observed in patients suffering from temporal lobe epilepsy and in several
      animal models of the disease. This lesion is duplicated in rats by a focal, intra
      entorhinal injection of the "indirect" excitotoxin aminooxyacetic acid (AOAA),
      providing a model that can be used to study the mechanisms underlying seizure
      induced cell death and epilepsy. Doomed neurons in the EC and in several
      associated limbic structures show pathological changes within hours after the
      AOAA injection, but GABAergic neurons in layer III of the EC are quite resistant.
      This pattern of neuron loss eventually results in hippocampal and entorhinal
      hyperexcitability. Notably, the seizure-induced death of layer III neurons in the
      EC can be attenuated by eliminating the prominent excitatory input from the
      presubiculum. Taken together, these results suggest opportunities to target
      parahippocampal structures for the treatment of temporal lobe epilepsy.

PMID- 10911884
TI  - The parahippocampal cortices and kindling.
AB  - The piriform and perirhinal cortices are parahippocampal structures with strong
      connections to limbic structures, including the amygdala and hippocampus, as well
      as other parahippocampal structures such as the entorhinal cortex. In this paper,
      we present results, based on anatomical, physiological, and kindling studies,
      that suggest that the perirhinal and piriform cortices might be very important in
      the secondary generalization of limbic seizures, particularly those with
      convulsive expression. These kindling data further suggest that the progressive
      lowering of afterdischarge thresholds in the parahippocampal structures, due to
      insult and/or genetic predisposition, might provide the neural basis for the
      clinical presentation of temporal lobe epilepsy.

PMID- 10911885
TI  - Memory deficits characterized by patterns of lesions to the hippocampus and
      parahippocampal cortex.
AB  - Spatial and nonspatial memory tests were given to patients with small thermal
      lesions administered to the medial temporal lobes in an attempt at alleviating
      pharmacologically resistant epilepsy. In all three spatial memory experiments
      presented in this paper, patients with lesions that included the right
      parahippocampal cortex were seriously impaired. Their impairment, together with
      the performance of patients with lesions to the right hippocampus (sparing the
      right parahippocampal cortex), provides the different patterns of deficits that
      lead to different interpretations of the function of the parahippocampal cortex.
      The distinction between the effects of functional damage in hippocampus and the
      effects of a lesion to the hippocampus or to regions surrounding the hippocampus,
      such as the parahippocampal cortex, is emphasized. We conclude that the right
      parahippocampal cortex participates in spatial memory beyond serving as a gateway
      to the hippocampus.

PMID- 10911886
TI  - Reciprocal connections between the amygdala and the hippocampal formation,
      perirhinal cortex, and postrhinal cortex in rat. A review.
AB  - Recent anterograde and retrograde studies in the rat have provided detailed
      information on the origin and termination of the interconnections between the
      amygdaloid complex and the hippocampal formation and parahippocampal areas
      (including areas 35 and 36 of the perirhinal cortex and the postrhinal cortex).
      The most substantial inputs to the amygdala originate in the rostral half of the
      entorhinal cortex, the temporal end of the CA1 subfield and subiculum, and areas
      35 and 36 of the perirhinal cortex. The amygdaloid nuclei receiving the heaviest
      inputs are the lateral, basal, accessory basal, and central nuclei as well as the
      amygdalohippocampal area. The heaviest projections from the amygdala to the
      hippocampal formation and the parahippocampal areas originate in the lateral,
      basal, accessory basal, and posterior cortical nuclei. These pathways terminate
      in the rostral half of the entorhinal cortex, the temporal end of the CA3 and CA1
      subfields or the subiculum, the parasubiculum, areas 35 and 36 of the perirhinal
      cortex, and the postrhinal cortex. The connectional data are summarized and the
      underlying principles of organization of these projections are discussed.

PMID- 10911887
TI  - Networks of the hippocampal memory system of the rat. The pivotal role of the
      subiculum.
AB  - The hippocampal system, consisting of the hippocampus, subiculum, and adjacent
      parahippocampal region, is known to play an important role in learning and memory
      processes. It is also known that the originally proposed trisynaptic circuit is a
      simplified representation of the organization of this system. In this paper, we
      present evidence, both anatomically and electrophysiologically, for the existence
      of direct and indirect parallel pathways through the hippocampal memory system
      arising from the perirhinal and postrhinal cortex. These pathways form nested
      loops. The subiculum occupies a central position within these loops. In the
      subiculum, both "raw" and highly processed information will converge. Therefore,
      we propose that the subiculum occupies a pivotal position in the hippocampal
      memory system, both as recipient and comparator of signals and as a distributor
      of processed information.

PMID- 10911888
TI  - Imaging epileptiform discharges in slices of piriform cortex with voltage
      sensitive fluorescent dyes.
AB  - Voltage imaging techniques were used to investigate epileptiform discharges in
      brain slices containing piriform cortex (PC). These experiments pinpointed the
      site of discharge onset in the endopiriform nucleus (En). Under some conditions,
      discharge onset also occurred simultaneously in adjoining neocortex. With
      slightly suprathreshold electrical stimulation, discharge generation was a two
      stage process in which onset was preceded by a sustained spatially localized
      depolarization denoted as plateau activity. Plateau activity was seen away from
      the onset site, in a border region between En and layer III of PC. A similar two
      stage sequence was seen for slices taken from a variety of planes, using two
      different interictal models as well as an ictal model. Plateau activity was found
      to be necessary for the generation of both kinds of discharge. Synaptic
      transmission at the site of onset was found to be required for the generation of
      interictal-like discharges, but ictal-like discharges were different in that they
      could still be generated when synaptic transmission at this site was impaired.
      These studies identify specialized regions with potentially important roles in
      epileptogenesis and help to elucidate the neuronal circuitry that can produce
      epileptiform activity.

PMID- 10911889
TI  - Computational modeling of entorhinal cortex.
AB  - Computational modeling provides a means for linking the physiological and
      anatomical characteristics of entorhinal cortex at a cellular level to the
      functional role of this region in behavior. We have developed detailed
      simulations of entorhinal cortical neurons and networks, with an emphasis on the
      role of acetylcholine in entorhinal cortical function. Computational modeling
      suggests that when acetylcholine levels are high, this sets appropriate dynamics
      for the storage of stimuli during performance of delayed matching tasks. In
      particular, acetylcholine activates a calcium-sensitive nonspecific cation
      current which provides an intrinsic cellular mechanism which could maintain
      neuronal activity across a delay period. Simulations demonstrate how this
      phenomena could underlie entorhinal cortex delay activity as described in
      previous unit recordings. Acetylcholine also induces theta rhythm oscillations
      which may be appropriate for timing of afferent input to be encoded in
      hippocampus and for extraction of individual stored sequences from multiple
      stored sequences. Lower levels of acetylcholine may allow sharp wave dynamics
      which can reactivate associations encoded in hippocampus and drive the formation
      of additional traces in hippocampus and entorhinal cortex during consolidation.

PMID- 10911890
TI  - Disruption of the ventral visual stream in a case of reduplicative paramnesia.

PMID- 10911892
TI  - Higher cortisol values facilitate spatial memory in toddlers. Brief report.

PMID- 10911891
TI  - Predator exposure produces retrograde amnesia and blocks synaptic plasticity.
      Progress toward understanding how the hippocampus is affected by stress.

PMID- 10911893
TI  - Functional characterization of hippocampal output to the entorhinal cortex in the
      rat.

PMID- 10911895
TI  - Age-related deficits in episodic memory may result from decreased responsiveness
      of hippocampal place cells to changes in context.

PMID- 10911894
TI  - Dopamine, serotonin, and noradrenaline strongly inhibit the direct perforant path
      CA1 synaptic input, but have little effect on the Schaffer collateral input.

PMID- 10911896
TI  - Presubicular input to the dendrites of layer-V entorhinal neurons in the rat.

PMID- 10911897
TI  - Perirhinal cortex and thalamic stimulation induces LTP in different areas of the
      amygdala.

PMID- 10911898
TI  - The parahippocampal region and auditory-mnemonic processing.

PMID- 10911899
TI  - Impaired sensory gating and attention in rats with developmental abnormalities of
      the mesocortex. Implications for schizophrenia.

PMID- 10911900
TI  - Morphometric MRI analysis of the parahippocampal region in temporal lobe
      epilepsy.
AB  - Despite neuropathological and electrophysiological evidence for the involvement
      of parahippocampal structures in temporal lobe epilepsy (TLE), little attention
      has been paid to morphometric changes in these structures, and the relation of
      these changes to TLE. We performed high-resolution MRI volumetric analysis to
      examine in vivo the morphology of the parahippocampal region in 20 healthy
      subjects and 6 TLE patients with MRI evidence of unilateral hippocampal atrophy.
      In normal controls the standardized volume of the left entorhinal cortex (EC) was
      1305 +/- 138 mm3 and that of the right EC was 1376 +/- 170 mm3; the left
      perirhinal cortex (PC) was 2900 +/- 554 mm3 and the right PC was 2771 +/- 486
      mm3; the left posterior parahippocampal cortex (PPC) was 2499 +/- 583 mm3 and the
      right PPC was 2234 +/- 404 mm3. Using a 2 standard deviation cutoff from the mean
      of normal controls, we found ipsilateral to the seizure focus: (i) a reduction in
      the volume of the EC in all patients; (ii) a reduction of the PC in 2/6 (33%)
      patients; (iii) no reduction in the volume of the PPC in any patient. In 3/6
      (50%) of patients, the EC was also abnormally small contralateral to the seizure
      focus. In patients with unilateral TLE, the EC is the most affected structure
      within the parahippocampal region. Whether this is due to a primary role of the
      EC in the genesis of TLE or is the consequence of its pivotal position in the
      reciprocal flow of information between the hippocampus and the neo- and limbic
      cortices remains to be explored.

PMID- 10911901
TI  - Translating the knowledge of molecular alterations that occur during colon
      carcinogenesis into clinically relevant solutions.

PMID- 10911902
TI  - Different pathways of colorectal carcinogenesis and their clinical pictures.
AB  - An entertaining debate in cancer genetics concerns the relative importance of
      selection for a growth advantage and genomic instability in tumorigenesis. Below,
      I present evidence that shows that selection is more important, particularly in
      the early stages of tumorigenesis, but that genomic instability is also an
      indisputable feature of many cancers. One attractive possibility is that some
      mutations may have pleiotropic effects both on cell replication or apoptosis and
      on genomic instability.

PMID- 10911903
TI  - Control of beta-catenin signaling in tumor development.
AB  - The wnt signal transduction pathway is involved in various differentiation events
      during embryonic development and leads to tumor formation when aberrantly
      activated. The wnt signal is transmitted to the nucleus by the cytoplasmic
      component beta-catenin: in the absence of wnts, beta-catenin is constitutively
      degraded in proteasomes, whereas in the presence of wnts beta-catenin is
      stabilized and can associate with HMG box transcription factors of the LEF/TCF
      family. The LEF/TCF/beta-catenin complexes activate specific wnt target genes. In
      tumors, beta-catenin degradation is blocked by mutations of beta-catenin or of
      the tumor suppressor gene product APC. As a consequence, beta-catenin is
      stabilized, constitutive complexes with LEF/TCF factors are formed, and oncogenic
      target genes, such as c-myc, cyclin D1, and c-jun, are activated. Thus, control
      of beta-catenin is a major regulatory event in normal wnt signaling and during
      tumor formation. It has been found that a multiprotein complex assembled by the
      cytoplasmic component conductin induces degradation of cytoplasmic beta-catenin.
      The complex includes APC, the serine/threonine kinase GSK3 beta, and beta
      catenin, which bind to conductin at distinct domains. In colon carcinoma cells,
      forced expression of conductin downregulates beta-catenin, whereas in normal
      cells mutants of conductin that are deficient in complex formation stabilize beta
      catenin. Fragments of APC that contain a conductin-binding domain also block beta
      catenin degradation. In Xenopus embryos, conductin inhibits the wnt pathway. In
      situ hybridization analysis shows that conductin is expressed in various
      embryonal tissues known to be regulated by wnts, such as the developing brain,
      mesenchyme below the epidermis, lung mesenchyme, and kidney. It is suggested that
      conductin controls wnt signaling by assembling the essential components of the
      beta-catenin degradation pathway. Alterations of conductin function may lead to
      tumor formation.

PMID- 10911904
TI  - Genetic testing for familial adenomatous polyposis.
AB  - Familial adenomatous polyposis (FAP, Mendelian Inheritance in Man number *175,100
      [edited by Victor A. McKusick], accessible on line under
      http:?www3.ncbi.nlm.nih.gov/htbin-post/ Omim/dispmim?175100) is a dominantly
      inherited colorectal cancer predisposition syndrome. The designation Gardner
      Syndrome is used for phenotypic variants of FAP with additional extracolonic
      symptoms. After the adenomatous polyposis coli (APC) gene was identified with the
      help of positional cloning strategies in 1991, it became evident that
      inactivation of this tumor suppressor is based on loss of carboxyterminal protein
      protein interaction domains. Identification of multiple molecular constituents
      binding to the distal half of the APC protein revealed its crucial involvement in
      wnt-signaling. Because the spectrum of mutations is predominated by small
      insertions and deletions, nonsense-, and splice-site mutations, a prescreening
      procedure is employed for the identification of germinal mutations in FAP
      patients that relies on in vitro synthesis of APC gene products, an approach also
      known under the acronym PTT (protein truncation test). Absence of nonsense
      mediated mRNA decay of mutated APC transcripts allows the application of a cDNA
      based coupled in vitro transcription/translation reaction for exons 1 to 14.
      Examination of four overlapping fragments from genomic DNA of probands reveals
      stops in the large APC exon 15, encompassing more than 6500 base pairs. Using
      this procedure, mutations causing the disease will be identified in about 80% of
      FAP patients. In the other cases of clinically manifest FAP, evidence exists that
      reduction of the steady state level of APC protein as a result of transcriptional
      silencing or large genomic deletions could provide for the clinical phenotype.
      Although some genotype-phenotype correlations have been described, exceptions
      from the rule have been reported, that is, for CHRPE. Modifier genes for the
      development of extracolonic manifestations are currently still enigmatic.
      Knowledge of such genes would essentially contribute to a better presymptomatic
      treatment of FAP patients.

PMID- 10911905
TI  - Molecular genetics of hereditary nonpolyposis colorectal cancer.
AB  - The initial paradigm developed for colorectal carcinogenesis was derived from the
      observation that these tumors suffer a large number of chromosomal losses. This
      phenomenon results from unbalanced mitoses, and to date there is no clear
      explanation for this type of genomic instability. In 1993, a second type of
      genomic instability was detected and linked to 12-15% of sporadic tumors, as well
      as 90% or more of the colon cancers in hereditary nonpolyposis colorectal cancer
      (HNPCC). HNPCC tumors are typically diploid and do not have the inactivating
      mutations at the tumor suppressor genes commonly found in the other cancers.
      These tumors were found because they have a very large number (perhaps in excess
      of 10(5)) of insertion or deletion mutations at microsatellite sequences; as a
      result, this has been termed microsatellite instability (MSI). The majority of
      HNPCC families can be linked to germline mutations in the DNA mismatch repair
      (MMR) genes hMSH2 or hMLH1. Germline mutations in hMSH6 and hPMS2 in HNPCC
      families are much less common. HNPCC tumors develop through the accumulation of
      mutations at genes that control cellular growth, and these genes are not the same
      as those recognized in the initial pathway outlined by Vogelstein et al. The
      genetic targets of MSI all contain repetitive sequences in coding regions that
      are unstable when the DNA MMR system is inoperative. Certain pathological
      features have been identified that suggest that colon cancers have developed in
      the setting of defective DNA MMR.

PMID- 10911906
TI  - Pathology of hereditary nonpolyposis colorectal cancer.
AB  - The magnitude of the pathologist's role in the diagnosis of hereditary
      nonpolyposis colorectal cancer (HNPCC) is underestimated. The diagnostic features
      are not specific to HNPCC cancers, but relate to all cancers showing high levels
      of DNA microsatellite instability (MSI-H). Three major groups of MSI-H cancers
      can be recognized by histopathological criteria: (1) right-sided poorly
      differentiated cancers, (2) right-sided mucinous cancers, and (3) adenocarcinomas
      in any location showing tumor-infiltrating (intraepithelial) lymphocytes (TIL).
      The poorly differentiated cancers are relatively well circumscribed and the cells
      are arranged in sheets or trabeculae. TIL may be very numerous in poorly
      differentiated cancers. The presence of TIL as estimated in H&E sections equates
      with a percentage of intraepithelial T cells (CD3+) in the range of 4 to 30%.
      Most of the T cells are CD8+ (cytotoxic T cells). Peritumoral lymphocytes and the
      so-called Crohn's-like reaction are associated with TIL, but are harder to
      quantify. Of the 15% of colorectal cancers that are MSI-H, 13% will be sporadic
      and 2% will occur in the context of HNPCC. HNPCC should be suspected if the
      patient is young (less than 55 years) because sporadic MSI-H cancers (associated
      with hypermethylation of the promoter region of hMLH1) occur almost exclusively
      in elderly subjects. Workup of a suspected case should include DNA microsatellite
      testing with a panel of mononucleotide (e.g., BAT26, BAT25) and dinucleotide
      (e.g., D5S346, D2S123, and D177S250) markers before referral to a cancer family
      or clinical genetics clinic. Immunohistochemical staining for hMLH1 and hMSH2
      identifies the underlying mutation in a proportion of cases. The colorectal
      adenoma is the usual precursor lesion in HNPCC, though serrated polyps are
      implicated in a small subset.

PMID- 10911907
TI  - Clinical aspects of hereditary nonpolyposis colorectal cancer.

PMID- 10911908
TI  - Use of representational difference analysis and cDNA arrays for transcriptional
      profiling of tumor tissue.
AB  - Representational difference analysis of cDNA (cDNA-RDA) was used for a comparison
      of the global transcript level of tumor of the larynx and the corresponding
      normal epithelial tissue toward the end of detecting differentially expressed
      genes. Overall, some 130 gene fragments were identified. By sequence analysis and
      homology comparison, they could be put into several groups related to (potential)
      functions. Apart from genes whose overexpression was most likely a result of
      tumor growth or dedifferentiation of epithelial tissue, a lot of genes were
      isolated that play major roles in signal transduction pathways or apoptosis or
      act as oncogenes or tumor suppressor genes, in addition to new, entirely unknown
      genes. Moreover, some cDNAs of known genes were identified that derived from
      unconventional splicing activity or other transcript modifications. All
      identified fragments were arrayed on solid support and used for reverse Northern
      blot analyses. The use of preselected RDA fragments as targets in array-based
      profiling experiments circumvents many of the problems encountered when dealing
      with large clone libraries.

PMID- 10911909
TI  - CD44 acts both as a growth- and invasiveness-promoting molecule and as a tumor
      suppressing cofactor.
AB  - High-molecular-weight splice variants of the CD44 transmembrane protein family
      have been implicated in tumorigenesis and metastasis formation. By contrast, in
      certain tumors--for example, Burkitt's lymphoma, neuroblastomas, and prostate
      cancer--loss of CD44 expression seems to accompany transformation. Here we
      describe two modes of action of CD44 proteins. They can bind growth factors and
      present them to their authentic high-affinity receptors, and thus promote
      proliferation and invasiveness of cells. Under these conditions the CD44 proteins
      recruit ERM proteins--for example, ezrin or moesin--to their cytoplasmic tails,
      thereby producing links to the cytoskeleton. This mode of action could account
      for the tumor-promoting action of CD44 proteins. The second mode of action of
      CD44 proteins comes into play when cells reach confluent growth conditions. Under
      specific conditions, binding of another ligand, the ECM component hyaluronate,
      leads to the activation and binding to the CD44 cytoplasmic tail of the tumor
      suppressor protein merlin. The activation of merlin confers growth arrest, so
      called contact inhibition. This function of CD44 proteins defines them as tumor
      suppressors. The type of action of CD44 on a given cell will depend on the
      isoform pattern of CD44 expressed, on the cellular equipment with ERM protein
      members, on the nature of the ECM, and on yet-unknown conditions.

PMID- 10911910
TI  - The p53 tumor suppressor gene: from molecular biology to clinical investigation.
AB  - The tumor suppressor p53 is a phosphoprotein barely detectable in the nucleus of
      normal cells. Upon cellular stress, particularly that induced by DNA damage, p53
      can arrest cell cycle progression, thus allowing the DNA to be repaired; or it
      can lead to apoptosis. These functions are achieved, in part, by the
      transactivational properties of p53, which activate a series of genes involved in
      cell cycle regulation. In cancer cells bearing a mutant p53, this protein is no
      longer able to control cell proliferation, resulting in inefficient DNA repair
      and the emergence of genetically unstable cells. The most common changes of p53
      in human cancers are point missense mutations within the coding sequences of the
      gene. Such mutations are found in all major histogenetic groups, including
      cancers of the colon (60%), stomach (60%), breast (20%), lung (70%), brain (40%),
      and esophagus (60%). It is estimated that p53 mutations are the most frequent
      genetic event in human cancers, accounting for more than 50% of cases. One of the
      most striking features of the inactive mutant p53 protein is its increased
      stability (half-life of several hours, compared to 20 min for wild-type p53) and
      its accumulation in the nucleus of neoplastic cells. Therefore, positive
      immunostaining is indicative of abnormalities of the p53 gene and its product.
      Several studies have shown that p53 mutations are associated with short survival
      in colorectal cancer, but the use of p53 as a tumoral marker is still a matter of
      debate.

PMID- 10911911
TI  - The epigenetics of colorectal cancer.
AB  - Colorectal cancer has provided an excellent model for studying the genetic basis
      of cancer and is one of the better-understood malignancies in this regard. The
      orderly progression of the disease, with distinct genetic alterations at each
      step, is a useful framework for deciphering the molecular basis of neoplasia.
      Epigenetics, the study of clonal changes in gene expression without associated
      genetic lesions, has raised increased interest recently, in part because of the
      identification of DNA methylation as a potential molecular mediator of the
      process. Several tumor-suppressor genes are silenced in various neoplasms in
      association with aberrant promoter methylation, and in the absence of coding
      region mutations. The study of DNA methylation changes in colorectal cancer has
      now provided additional clues into the pathogenesis of the disease. This review
      presents evidence for a model whereby DNA methylation changes play two distinct
      roles in the molecular evolution of colorectal cancer. Initially, progressive
      methylation and silencing of a subset of genes takes place in normal tissues as a
      function of age or time-dependent events and predisposes these normal cells to
      neoplastic transformation. At a later stage of disease progression, DNA
      methylation plays an important role in a subset of tumors affected by the CpG
      island methylator phenotype (CIMP), a recently identified pathway that results in
      a form of epigenetic instability through the simultaneous silencing of multiple
      genes. DNA methylation changes have important interactions with genetic lesions
      in this cancer type. CIMP+ cancers include the majority of tumors with sporadic
      mismatch repair deficiency through hypermethylation of the hMLH1 promoter, and
      also account for the majority of tumors with Ki-ras mutations through an unknown
      mechanism. By contrast, CIMP- cases evolve along a more classic genetic
      instability pathway, with a high rate of p53 mutations and chromosomal changes.
      Thus, the integration of epigenetic and genetic information provides a more
      complete molecular understanding of colorectal cancer and may have implications
      for the diagnosis, prognosis, and treatment of patients affected by this disease.

PMID- 10911912
TI  - How does DNA methyltransferase cause oncogenic transformation?
AB  - Global hypomethylation of genes and repetitive sequences, as well as
      hypermethylation of certain genes known to be involved in tumor suppression, are
      observed concurrently in cancer cells. Aberrant expression of DNA
      methyltransferase 1 (dnmt1) is a downstream effector of multiple tumorigenic
      pathways, and several data suggest that dnmt1 plays a causal role in these
      pathways. These data raise two critical questions: Why does ectopic expression of
      dnmt1 transform cells? and How can global hypomethylation exist in a cell that
      bears high levels of DNMT1 activity? It is proposed that DNMT1 induces cellular
      transformation by a mechanism that does not involve DNA methylation and that the
      low level of methylation in cancer cells is a result of induction of a DNA
      demethylase in these cells. Both DNMT1 and the demethylase play a causal role in
      cellular transformation and are candidate anticancer targets.

PMID- 10911913
TI  - Altered mechanisms of apoptosis in colon cancer: Fas resistance and counterattack
      in the tumor-immune conflict.
AB  - Fas (CD95/APO-1) is a cell surface "death receptor" that mediates apoptosis upon
      engagement by its ligand, FasL. Fas-mediated apoptosis of lymphocytes normally
      serves immunoregulatory roles, including tolerance acquisition, immune response
      termination, and maintenance of immune privilege in certain organs. Colon tumors
      can exploit this lymphocyte death program by expressing FasL. This may enable
      colon tumors to mount a "Fas counterattack" against antitumor lymphocytes,
      impairing antitumor immune responses. FasL-expressing colon tumor-derived cell
      lines can trigger Fas-mediated apoptosis of cocultured T cells in vitro. FasL
      expressed in esophageal cancer has been significantly associated with apoptosis
      and depletion of tumor-infiltrating lymphocytes (TIL) in vivo. FasL may also
      facilitate metastatic colonization of Fas-sensitive organs such as the liver, by
      inducing apoptosis of target organ cells. Normal colonic epithelial cells express
      Fas and are relatively sensitive to Fas-mediated apoptosis. By contrast, colon
      tumor-derived cell lines are usually resistant to induction of Fas-mediated
      apoptosis, and colon cancer cells frequently coexpress Fas and FasL. The
      mechanisms allowing resistance to Fas-mediated apoptosis are complex, and defects
      have been identified at several levels of Fas signal transduction. The "Bcl-2
      rheostat" may be pitched against apoptosis in colon cancer, inasmuch as
      overexpression of Bcl-2, downregulation of Bak, and mutation of Bax are common
      defects in colon tumors. Caspase-1 is also downregulated in colon cancer. The
      high frequency of p53 mutations in late-stage cancers may also inhibit Fas
      signaling. Fundamental defects in apoptosis signaling may contribute to both
      immuno- and chemoresistance in colon cancer and allow expression of FasL to
      counterattack antitumor lymphocytes.

PMID- 10911914
TI  - Translational studies on Cox-2 inhibitors in the prevention and treatment of
      colon cancer.
AB  - Inhibitors of the inducible cyclooxygenase (COX-2) have emerged as a promising
      new class of drugs that may be useful for the prevention of colorectal cancer.
      Experimental evidence to support such a claim has come from both clinical and
      laboratory findings that show that both selective and nonselective COX inhibitors
      effectively block tumor growth. Although the precise mechanism(s) by which these
      drugs modulate tumor growth is not known, there is evidence from colon carcinoma
      cell culture studies that COX-2 activity may play an important role in regulating
      angiogenesis and apoptosis. Recent data obtained in animal studies suggest that
      COX-2 inhibitors may also be useful in the treatment of established colorectal
      tumors. Treatment of COX-2 expressing tumor cells with selective COX-2 inhibitors
      appears to reset the balance between cell proliferation and cell death such that
      there is no increase in tumor volume.

PMID- 10911915
TI  - Inhibition of CDKs as a therapeutic modality.
AB  - Altered cell cycle control has emerged as a recurring theme in neoplasia.
      Strategies that would return toward normal the altered cell cycle control present
      in tumor cells have appeal as novel approaches to cancer treatment. Cyclin
      dependent kinases (CDKs) control the progression through the cell cycle,
      operating at the transition from the G2 to M and G1 to S phases, and progression
      through S. CDKs are regulated by a complex set of mechanisms, including the
      presence of activating cyclins, regulatory phosphorylations, and endogenous CDK
      inhibitors at "checkpoints." This overview focuses on progress in defining
      compounds that can antagonize directly the action of CDKs. These have emerged as
      various types of ATP site-directed inhibitors, including flavopiridol, N
      substituted adenine derivatives, the natural product butyrolactone, staurosporine
      derivatives, and, more recently, the synthetic paullones. Paullones appear to be
      of interest in that one of the most active members of the class, 9-nitropaullone
      (alsterpaullone), requires relatively brief periods of exposure to living cells
      in order to effect lasting effects on cellular and proliferative potential. Two
      of these compounds, flavopiridol and UCN-01 (7-hydroxy-staurosporine), have
      entered early clinical trials and achieved concentrations that might potentially
      modulate CDK function. In the case of UCN-01, unexpected human plasma protein
      binding might prevent direct inhibition of CDKs but allow drug concentrations to
      be achieved that indirectly affect CDKs by checkpoint abrogation. Further studies
      with CDK inhibitors should define the expected end point of CDK inhibition more
      clearly in preclinical models and clinical systems, including cytostasis,
      apoptosis, or differentiation.

PMID- 10911916
TI  - p53: a potential target antigen for immunotherapy of cancer.
AB  - Approximately 50% of all human malignancies exhibit mutation and aberrant
      expression of p53, making this protein an interesting candidate target for
      immunotherapy of cancer. Mutations in p53 are highly diverse. Therefore,
      targeting of determinants within the wild-type p53 sequence appears most
      practical. Despite the fact that p53 is ubiquitously expressed, adoptive
      immunotherapy of tumor-bearing mice with p53-specific cytotoxic T lymphocytes
      (CTL) results in eradication of p53-overexpressing tumors in the absence of
      immunopathological damage to normal tissues. These CTL also eliminate tumors that
      do not show greatly enhanced expression of p53, indicating that the sensitivity
      of these tumors for p53-specific CTL is determined by the efficiency by which p53
      derived peptides are processed into class I MHC, rather than by the steady state
      levels of p53. Of note, although p53-specific CTL can readily be isolated from
      p53-/- mice, tolerance for this self antigen may prevent induction of similarly
      effective CTL in p53+/+ subjects. The T helper (Th) branch of the p53-specific
      immune response does not seem to be profoundly affected by tolerance. In
      addition, more and more evidence is obtained for the pivotal role of tumor
      specific Th cells in the induction and effector phases of the antitumor response,
      also against tumors that lack class II MHC expression. The efficacy of Th cells,
      specific for a recently identified class II MHC-restricted p53 peptide, against
      p53-overexpressing tumors is currently being investigated. In addition, natural
      and induced Th responses are analyzed both in a murine tumor model and in a phase
      I clinical trial involving p53-specific vaccination of colon cancer patients.

PMID- 10911917
TI  - Colorectal cancer vaccines: antiidiotypic antibody, recombinant protein, and
      viral vector.
AB  - The colorectal cancer antigen GA733 (also termed CO17-1A, KSI-4, Ep-CAM, KSA) has
      proved to be a useful target in passive immunotherapy with monoclonal antibody
      and in active immunotherapy with antiidiotypic antibodies in cancer patients. The
      GA733 antigen was molecularly cloned and expressed in baculovirus (BV),
      adenovirus (AV), and vaccinia virus (VV). Recombinant BV-, VV-, and AV-GA733
      induced antigen-specific cytotoxic antibodies and proliferative and delayed-type
      hypersensitive lymphocytes. However, only the AV recombinant induced antigen
      specific cytolytic T lymphocytes and regression of established tumors. Cured mice
      were protected against challenge with antigen-negative tumors, indicating antigen
      spreading of immune responses. In a model of active immunotherapy against the
      murine homologue of the human GA733 antigen, murine epithelial glycoprotein
      (mEGP), BV-derived mEGP protein in various adjuvants did not protect mice against
      a challenge with mEGP-positive tumors. AV mEGP, only when combined with
      interleukin-2, significantly inhibited growth of established mEGP-positive
      tumors. This is in contrast to the same vaccine expressing the human antigen that
      was effective without interleukin-2. AV GA733, in combination with interleukin-2,
      is a candidate vaccine for colorectal cancer patients.

PMID- 10911918
TI  - Ga733/EpCAM as a target for passive and active specific immunotherapy in patients
      with colorectal carcinoma.
AB  - GA733/EpCAM is an oncofetal antigen abundantly expressed in colorectal carcinoma.
      This antigen can spontaneously induce a humoral and cellular antitumor immunity
      and may therefore be a suitable target structure for immunotherapy. Patients with
      advanced colorectal carcinoma have been treated with monoclonal antibodies (MAb17
      1A) against this structure. The data indicate that the chimeric variant was not
      superior to the original mouse MAb. Addition of cytokines and chemotherapeutics
      may improve the therapeutic effect of the MAb. A particularly interesting regimen
      is a combination of MAb17-1A/GM-CSF/alpha-IFN/5-Fu. The GA733 protein antigen can
      also be used as a vaccine. Patients with colorectal carcinoma stages B and C were
      vaccinated with this protein antigen in combination with GM-CSF as an adjuvant
      cytokine. A strong type I T cell response was induced that seemed to be MHC class
      I as well as class II restricted. No systemic side effects were noted.

PMID- 10911919
TI  - Radioimmunotherapy of colorectal cancer liver metastases: combination with
      radiotherapy.
AB  - The expected therapeutic gain of a combined radioimmunotherapy (RIT) with
      conventional radiotherapy (RT) would be a synergy of tumor irradiation, provided
      that toxic, dose-limiting side effects concern different organs. We have shown in
      a model of subcutaneous human colon cancer transplants in nude mice that RIT with
      131I-labeled anti-CEA antibody fragments combined with fractionated RT give an
      additive therapeutic effect without increase of side effects. A second study of
      different timing schedules of RIT and RT has shown that close association of both
      therapies without delay is more efficient than a therapy with a treatment-free
      interval of two weeks. In a new model of human colon cancer liver metastases in
      nude mice, early treatment with RIT and with RT has been curative, whereas
      therapies initiated later were less efficient, suggesting that the combined
      therapy is likely to be more efficient in an adjuvant situation after surgery. At
      the clinical level, six patients with limited liver metastatic disease from
      colorectal cancer were treated with RIT using 200 mCi 131I-labeled anti-CEA MAb
      F(ab')2 fragments combined with fractionated external beam RT of 20 Gy to the
      entire liver. As expected, spontaneously reversible bone marrow toxicity grade 3
      to 4 and reversible liver toxicity grade 1 to 3 have been observed. By
      computerized tomography, three patients showed stable disease and one patient
      partial remission, whereas two patients had progressive disease. In conclusion,
      animal experiments have shown a clear advantage of combined RT and RIT, and the
      clinical study shows the feasibility of such a therapy in patients with
      colorectal cancer liver metastases.

PMID- 10911920
TI  - Partial opioids. Medications for the treatment of pain and drug abuse.
AB  - Pentazocine and cyclazocine are two benzomorphans that were synthesized by the
      late Sydney Archer in 1962. These benzomorphans were synthesized as part of an
      effort to develop analgesics with little or no abuse potential. Pentazocine is
      used as an analgesic, often in individuals who have sever pain or in those who
      have drug-abuse problems. Cyclazocine is a low-liability analgesic and potential
      therapeutic for the treatment of drug abuse. The risk of drug dependence is lower
      with the benzomorphans, which usually act as partial agonists at the mu opioid
      receptor and as kappa agonists. In an attempt to synthesize analogs of
      cyclazocine with increased bioavailability and varying kappa agonist and partial
      mu agonist properties, a series of 8-amino derivatives of cyclazocine were
      synthesized. These compounds were characterized in radioligand binding assays for
      their affinity and selectivity for the mu, delta, and kappa opioid receptors.
      Mouse antinociceptive tests were used to characterize the agonist and antagonist
      properties of each compound at the mu, delta and kappa receptors.

PMID- 10911921
TI  - Spinal and supraspinal mechanisms of neuropathic pain.
AB  - Neuropathic pain is associated with abnormal tactile and thermal responses that
      may be extraterritorial to the injured nerve. Importantly, tactile allodynia and
      thermal hyperalgesia may involve separate pathways, since complete and partial
      spinal cord lesions have blocked allodynia, but not hyperalgesia, after spinal
      nerve ligation (SNL). Furthermore, lesions of the dorsal column, and lidocaine
      microinjected into dorsal column nuclei block only tactile allodynia. Conversely,
      thermal hyperalgesia, but not tactile allodynia was blocked by desensitization of
      C-fibers with resiniferotoxin. Therefore, it seems that tactile allodynia is
      likely to be mediated by large diameter A beta fibers, and not susceptible to
      modulation by spinal opioids, whereas hyperalgesia is mediated by unmyelinated C
      fibers, and is sensitive to blockade by spinal opioids. Additionally, abnormal,
      spontaneous afferent drive in neuropathic pain may contribute to NMDA-mediated
      central sensitization by glutamate and by non-opioid actions of spinal dynorphin.
      Correspondingly, SNL elicited elevation in spinal dynorphin content in spinal
      segments at and adjacent to the zone of entry of the injured nerve along with
      signs of neuropathic pain. Antiserum to dynorphin A(1-17) or MK-801 given
      spinally blocked thermal hyperalgesia, but not tactile allodynia, after SNL, and
      also restored diminished morphine antinociception. Finally, afferent drive may
      induce descending facilitation from the rostroventromedial medulla (RVM).
      Blocking afferent drive with bupivicaine also restored lost potency of PAG
      morphine, as did CCK antagonists in the RVM. This observation is consistent with
      afferent drive activating descending facilitation from the RVM, and thus
      diminishing opioid activity, and may underlie the clinical observation of limited
      responsiveness of neuropathic pain to opioids.

PMID- 10911922
TI  - A third life for burimamide. Discovery and characterization of a novel class of
      non-opioid analgesics derived from histamine antagonists.
AB  - Burimamide, a histamine (HA) derivative with both H2- and H3-blocking properties,
      induces antinociception when injected into the rodent CNS. Several related
      compounds share this property, and structure-activity studies have shown that
      this new class of analgesics is distinct from known HA antagonists. The
      prototype, named improgan, shows a preclinical profile of a highly effective
      analgesic, with activity against thermal, mechanical and inflammatory nociception
      after doses that do not alter motor balance or locomotor activity. Improgen
      analgesia is not blocked by opioid antagonists and is observed in opioid receptor
      knock-out mice. Unlike morphine, improgan does not induce tolerance after daily
      dosing. Extensive in vitro pharmacology studies have excluded known
      histaminergic, opioid, serotonergic, GABAergic and adrenergic receptor
      mechanisms, as well as 50 other sites of action. The improgan-like analgesic
      activity of some HA congeners suggests an analgesic action on a novel HA
      receptor, but further studies are required to substantiate this. Studies in
      progress are characterizing the sites and mechanisms of action of improgan, and
      developing brain-penetrating derivatives that could be useful for clinical pain.

PMID- 10911923
TI  - Peripheral opioid modulation of visceral pain.
AB  - Opioids are widely and successfully used for control of pain, including pain
      arising from the viscera. Constipating, sedating, respiratory depressant and
      other effects of opioids, however, often limit their long-term use in the
      treatment of a variety of visceral pain states. Accordingly, understanding
      visceral pain mechanisms and its modulation is important to developing improved
      strategies for pain control.

PMID- 10911925
TI  - Development of novel medications for drug addiction. The legacy of an African
      shrub.
AB  - Ibogaine, one of several alkaloids found in the root bark of the African shrub
      Tabernanthe iboga, has been claimed to be effective in treating multiple forms of
      drug abuse. Problems associated with side effects of ibogaine have spawned a
      search for more effective and safer structural derivatives. 18
      Methoxycoronaridine (18-MC), a novel iboga alkaloid congener, appears to have
      substantial potential for broad use as an anti-addictive therapy. Like ibogaine
      (40 mg/kg), 18-MC (40 mg/kg) decreases the intravenous self-administration of
      morphine and cocaine and the oral self-administration of ethanol and nicotine in
      rats; unlike ibogaine, 18-MC does not affect responding for a non-drug reinforcer
      (water). Ibogaine and 18-MC appear to reduce the reinforcing efficacies, rather
      than the potencies, of drugs of abuse. Both ibogaine and 18-MC decreases
      extracellular levels of dopamine in the nucleus accumbens while only ibogaine
      increases serotonin levels in this brain region. Both ibogaine and 18-MC block
      morphine-induced and nicotine-induced dopamine release in the accumbens; only
      ibogaine enhances cocaine-induced increases in dopamine levels. Ibogaine produces
      whole body tremors and, at high doses (at least 100 mg/kg), cerebellar damage; 18
      MC does not produce these effects. Ibogaine, but not 18-MC, causes bradycardia at
      high doses. Ibogaine and its metabolite noribogaine have low microM affinities
      for kappa and mu opioid receptors, NMDA receptors, 5HT-3 receptors, sigma-2
      sites, sodium channels and the serotonin transporter. 18-MC has low microM
      affinities at all three opioid receptors and at 5HT-3 receptors but much lower or
      no affinities for NMDA and sigma-2 receptors, sodium channels, and the 5HT
      transporter. Both 18-MC and ibogaine are sequestered in fat and, like ibogaine,
      18-MC probably has an active metabolite. 18-MC also has (+) and (-) enantiomers,
      both of which are active. Considered together, all of the data indicate that 18
      MC should be safer than ibogaine and at least as efficacious as an anti-addictive
      medication.

PMID- 10911924
TI  - Neurobiological adaptations to psychostimulants and opiates as a basis of
      treatment development.
AB  - Abuse of illicit substances, in particular psychostimulants and opiates, is a
      worldwide public health issue. Chronic use of cocaine and amphetamine causes
      common neurobiological adaptations that may guide new treatment development.
      These include perturbations in dopamine and serotonin neurotransmission, leading
      to trials of antidepressants, and serotonin and dopamine augmentation strategies.
      The detection of cerebral perfusion abnormalities caused by psychostimulants has
      led to examination of antiplatelet and excitatory amino acid (EAA) antagonist
      therapies. Further, development of cocaine vaccines allows for testing of
      peripheral blockade approaches to cocaine addiction. New approaches to behavioral
      treatments for cocaine dependence are also reviewed. For opiate dependence,
      understanding of heroin's effects on mu and kappa opiate receptors has led to
      investigations of the partial mu agonist buprenorphine in opiate maintenance.
      Evidence for hyper-excitability of locus coeruleus (LC) noradrenergic neurons and
      EEA inputs to the LC guides trials of new alpha 2-adrenergic agonists and EEA
      antagonists to alleviate opiate withdrawal. Finally, clinical experience with
      withdrawal from methadone and LAAM has led to trials of antagonist-accelerated
      opiate withdrawal. Improved treatment of psychostimulant and opiate addiction is
      critically needed, and likely to have wide-reaching impact in health care and
      society.

PMID- 10911926
TI  - Interactions between kappa opioid agonists and cocaine. Preclinical studies.
AB  - Kappa opioid agonists inhibit dopamine release from mesolimbic dopaminergic
      neurons and attenuate some behavioral effects of cocaine in rodents. Evidence
      that kappa opioid agonists may act as functional antagonists of cocaine led us to
      examine their interactions with cocaine's abuse-related effects in rhesus
      monkeys. In cocaine self-administration studies, four arylacetamides (U50,488,
      enadoline, (-) spiradoline and PD117302) and four benzomorphans
      (ethylketocyclazocine [EKC], bremazocine, Mr2033 and cyclazozine) each were
      administered as continuous infusions over 10 days. EKC, Mr2033, bremazocine,
      U50,488 and enadoline produced significant dose-dependent and sustained decreases
      in cocaine self-administration and also decreased food-maintained responding at
      some doses. Emesis and sedation were occasionally observed during the first two
      days of kappa agonist treatment, but tolerance developed rapidly to these
      effects. Cyclazocine, PD117302 and spiradoline did not significantly alter
      cocaine self-administration. The behavioral effects of EKC and U50,488 were
      antagonized by both the kappa opioid antagonist nor-binaltorphimine and the non
      selective opioid antagonist naloxone. In general, compounds with mixed activity
      at both kappa and mu opioid receptors (e.g. EKC, Mr2033) decreased cocaine self
      administration more consistently and with fewer or less severe undesirable side
      effects than more selective kappa agonists (e.g. U50,488, spiradoline). Although
      several kappa agonists decreased cocaine self-administration, EKC and U50,488 did
      not consistently block the discriminative stimulus effects of cocaine in monkeys
      trained to discriminate cocaine from saline. The extent to which kappa agonist
      induced decreases in cocaine self-administration reflect an antagonism of
      cocaine's abuse-related effect remains to be determined.

PMID- 10911927
TI  - Effects of the novel D1 dopamine receptor agonist ABT-431 on cocaine self
      administration and reinstatement.
AB  - Selective D1 dopamine agonists represent a potential pharmacotherapy for the
      treatment of cocaine addiction. Here we report that systemic injections of the
      novel D1 agonist ABT-431 lack the ability to induce cocaine-seeking behavior, and
      completely attenuate the ability of cocaine to induce this behavior in rats
      tested in a reinstatement paradigm. Similar doses suppress the initiation of
      cocaine self-administration, and produce an extinction-like response pattern in
      animals that subsequently initiate self-administration, without altering
      responding maintained by food pellets. There was no tolerance to this effect over
      4 days of testing. The results suggest that ABT-431 attenuates the motivation to
      seek cocaine, and masks the reinforcing effects of cocaine during self
      administration. The profile of ABT-431 is similar to the behavioral effects of
      other structurally distinct D1 agonists, and is consistent with the desired
      profile of a "methadone-like" compounds for cocaine addiction.

PMID- 10911928
TI  - GABA modulation of cocaine self-administration.
AB  - Recent experiments suggest that GABA compounds produce a clinically relevant
      modulation of cocaine reinforcement. This review summarizes the results of a
      number of studies that examined the effect of the GABAB agonist baclofen on
      cocaine self-administration using a variety of schedules of reinforcement. The
      results demonstrate that baclofen causes a dramatic reduction in cocaine self
      administration which does not appear to be accounted for by a general disruption
      of behavior. However, the effect is dependent on the unit injection dose of
      cocaine and on the response requirements of the schedule. These results predict
      that in a clinical setting any potential therapeutic effect of baclofen will
      interact with the cost and availability of cocaine.

PMID- 10911929
TI  - Application of artificial enzymes to the problem of cocaine.
AB  - Cocaine mediates its reinforcing and toxic actions through a "loss of function"
      effect at multiple receptors. The difficulties inherent in blocking a pleiotropic
      blocker pose a great obstacle for the classical receptor-antagonist approach and
      have contributed to the failure-to-date to devise specific treatments for cocaine
      overdose and addiction. As an alternative, we have embarked on an investigation
      of catalytic antibodies, a programmable class of artificial enzyme, as
      "peripheral blockers"--agents designed to bind and degrade cocaine in the
      circulation before it partitions into the central nervous system to exert
      reinforcing or toxic effects. We synthesized transition-state analogs of
      cocaine's hydrolysis at its benzoyl ester, immunized mice, prepared hybridomas,
      and developed the first anti-cocaine catalytic antibodies with the capacity to
      degrade cocaine to non-reinforcing, non-toxic products. We subsequently
      identified several families of anti-cocaine catalytic antibodies and found that
      out most potent antibody, Mab15A10, possessed sufficient activity to block
      cocaine-induced reinforcement and sudden death in rodent models of addiction and
      overdose, respectively. With the potential to promote cessation of use, prolong
      abstinence, and provide a treatment for acute overdose, the artificial enzyme
      approach comprehensively responds to the problem of cocaine.

PMID- 10911930
TI  - Neurobiology of addiction. Toward the development of new therapies.
AB  - Drug addiction is a chronic relapsing brain disorder characterized by
      neurobiological changes that lead to a compulsion to take a drug with loss of
      control over drug intake. The hypothesis outlined here is that knowledge of the
      neurochemical systems involved in the transition from drug use to the compulsive
      use of addiction will provide the rational basis for development of
      pharmacotherapies for drug addiction. Much evidence has been obtained in
      identifying the midbrain-basal forebrain neural elements involved in the positive
      reinforcing effects of drugs of abuse and more recently in the neural elements
      involved in the negative reinforcement associated with drug addiction. Key
      elements for the acute reinforcing effects of drugs of abuse include a
      macrostructure in the basal forebrain called the extended amygdala that contains
      parts of the nucleus accumbens and amgydala and involves key neurotransmitters
      such as dopamine, opioid peptides, serotonin, GABA, and glutamate. Withdrawal
      from drugs of abuse is associated with subjective symptoms of negative affect,
      such as dysphoria, depression, irritability and anxiety, and dysregulation of
      brain reward systems involving some of the same neurochemical systems implicated
      in the acute reinforcing effects of drugs of abuse. In addition, acute withdrawal
      is accompanied by recruitment of the brain stress neurotransmitter system,
      corticotropin-releasing factor. Animal models of craving involve not only
      conditioning models but also models of excessive drug intake during prolonged
      abstinence, post-acute withdrawal, that may reflect continued dysregulation of
      drug reinforcement that could lead to vulnerability to relapse and represent an
      important focus for pharmacotherapy. Such changes have been hypothesized to
      involve a change in set point for drug reward that may represent an allostatic
      state contributing to vulnerability to relapse and re-entry into the addiction
      cycle. Elucidation of the specific neuropharmacological changes contributing to
      this prolonged functional dysregulation will be the challenge of future research
      on the neurobiology of drug addiction.

PMID- 10911931
TI  - Methadone-related opioid agonist pharmacotherapy for heroin addiction. History,
      recent molecular and neurochemical research and future in mainstream medicine.
AB  - In 1963, Professor Vincent P. Dole at the Rockefeller University formed a small
      team to develop a pharmacotherapy for the management of heroin addiction. They
      hypothesized that heroin addiction is a disease of the brain with behavioral
      manifestations, and not merely a personality disorder or criminal behavior and
      began to address the specific question of whether a long-acting opioid agonist
      could be used in the long-term maintenance treatment of heroin addiction. Over
      the next 35 years, many studies documented the safety, efficacy and effectiveness
      of methadone pharmacotherapy for heroin addiction, but Federal regulations and
      stigmatization of heroin addiction prevented implementation of treatment.
      Finally, in 1999, NIH published a report unequivocally supporting methadone
      maintenance pharmacotherapy for heroin addiction. Two other effective opioid
      agonist treatments have been developed: the even longer acting opioid agonist l
      alpha-acetylmethadol (LAAM) has been approved for pharmacotherapy for heroin
      addiction, and still under study is the opioid partial agonist-antagonist
      buprenorphine-naloxone combination. A variety of studies, both laboratory based
      and clinical, have revealed the mechanisms of action of long-acting opioid
      agonists in treatment, including prevention of disruption of molecular, cellular
      and physiologic events and, in fact, allowing normalization of those functions
      disrupted by chronic heroin use. Recent molecular biological studies have
      revealed single nucleotide polymorphisms of the human mu opioid receptor gene;
      the mu opioid receptor is the site of action of heroin, the major opiate drug of
      abuse, analgesic agents such as morphine, and the major treatment agents for
      heroin addiction. These findings support the early hypotheses of our laboratory
      that addiction may be due to a combination of genetic, drug-induced and
      environmental (including behavioral) factors and also, that atypical stress
      responsivity may contribute to the acquisition and persistence of, as well as
      relapse to, use of addictive drugs.

PMID- 10911932
TI  - Prenatal cocaine exposure.
AB  - Cocaine abuse is a significant problem not only in the general population but
      also among pregnant women. Since cocaine readily crosses the placenta and is
      metabolized slowly in fetuses, they can be exposed to significant levels of
      cocaine for long periods. In humans the most common consequences of cocaine abuse
      during pregnancy include premature birth, lower birth weight, respiratory
      distress, bowel infarctions, cerebral infarctions, reduced head circumference,
      and increased risk of seizures. Behaviorally these newborns show an increased
      degree of "tremulousness," crying and irritability, and are over-reactive to
      environmental stimuli. Within a month these behaviors have recovered
      dramatically, but not to normal levels. Thus while there are a number of
      abnormalities associated with cocaine-exposed neonates, they are not imminently
      debilitating or life-threatening. However, the long-term consequences of this
      prenatal cocaine exposure remain to be elucidated. We have examined a rat model
      for neurochemical, neuroanatomical and behavioral changes resulting from prenatal
      cocaine exposure. Since cocaine is known to act by blocking the inactivation of
      the neurotransmitters dopamine, serotonin and norepinephrine, our studies have
      focused on brain dopamine (DA) and serotonin (5-HT) pathways. In this model
      system we have found neurochemical changes that are present at birth and that
      return to normal as the rat ages--similar to the recovery observed in infants.
      However, there are other neurochemical, anatomical and behavioral changes that
      persist after birth which may provide insights into the long-term consequences.
      It is hoped that by understanding the changes occurring in this rat model we will
      be better prepared to devise pharmacological interventions to circumvent the
      secondary consequences of prenatal cocaine exposure. These consequences might
      include increased susceptibility to drug addiction, seizures, depression,
      schizophrenia, Parkinson's disease, etc.

PMID- 10911934
TI  - Tobacco dependence. Global public health potential for new medications
      development and indications.
AB  - Current trends indicate that approximately 500 million of the world's existing
      cigarette smokers will prematurely die of causes that could be prevented by
      treatment of their addiction to tobacco delivered nicotine. Initial
      pharmacologically based treatment offerings and approaches have proven the
      concept that increasing the accessibility and diversity of treatment modalities
      helps more people quit smoking. These treatments have also shown, however, that
      the vast majority of smokers continues to find treatment less attractive and less
      accessible than cigarettes whose appeal is constantly stimulated by new
      formulations, marketing strategies, and implied claims of reduced risk. There
      appears to be considerable untapped potential public health benefit, as well as
      commercial opportunity, for medication developers to reach an increasing fraction
      of smokers who find current treatments unacceptable, inaccessible, or
      ineffective. The global opportunities to serve public health via medication
      development are growing even more rapidly as country after country recognizes the
      impending economic and health care problems posed by tobacco dependence and are
      opening their doors to treatment. Three areas of medications development offer
      particular promise: new forms of nicotine delivery, non-nicotine based
      medications, and new indications to reach those who are unable or unwilling to
      completely quit. This article discusses the biobehavioral rationale for
      medication development, the opportunities, and some of the prominent technical
      and regulatory challenges.

PMID- 10911933
TI  - Mimicking gene defects to treat drug dependence.
AB  - The genetic basis for drug dependence has focused on genes that encode receptors
      involved in the reinforcing properties of drugs of abuse or that determine drug
      taking behavior (e.g. impulsivity, etc.). Pharmacogenetic variations in the
      patterns of metabolism among individuals can also importantly modulate the risk
      of drug dependence. Cytochrome P450 drug metabolizing enzymes (CYPs), can
      activate (e.g. codeine to morphine) or deactivate (e.g. nicotine to cotinine)
      drugs of abuse. Some CYPs are polymorphic, that is, there are gene mutations
      which result in individuals with no (null mutations) or decreased enzyme activity
      (e.g. CYP2D6*10). Individuals with two null mutations appear in the population as
      phenotypic poor metabolizers. Using in vitro studies, we have identified drugs of
      abuse that are substrates of the polymorphic enzymes CYP2D6 (codeine,
      amphetamines, dextromethorphan), CYP2A6 (nicotine) and CYP2C19 (flunitrazepam).
      In human experimental studies, we have shown that CYP phenotype and genotype
      affect abuse liability of CYP2D6 metabolized drugs of abuse. In addition, we
      inhibited CYP2D6 and decreased individuals' risk of dependence experimentally
      (codeine, dextromethorphan) and treated codeine dependence. In epidemiologic
      studies CYP2D6 and CYP2A6 null mutations protect individuals from becoming
      codeine and tobacco dependent, respectively. With respect to CYP2A6, individuals
      with mutations, smoke fewer cigarettes and can quit more easily. Inhibiting
      CYP2A6 (e.g. tranylcypromine, methoxsalen) decreases smoking and the activation
      of procarcinogens. By mimicking these gene defects the risk of dependence can be
      decreased in individuals and new treatments developed.

PMID- 10911935
TI  - Ibogaine in acute opioid withdrawal. An open label case series.

PMID- 10911937
TI  - Pharmacological profiles of kappa opioids. Correlation between [35S]GTP gamma S
      binding and cyclic AMP production.

PMID- 10911936
TI  - Methamphetamine quantitative urine concentrations during a controlled trial of
      fluoxetine treatment. Preliminary analysis.

PMID- 10911938
TI  - Synchronous activity in the ventral tegmental area and prefrontal cortex.

PMID- 10911939
TI  - Histamine modulation of nucleus accumbens neurons.

PMID- 10911940
TI  - Dopaminergic mechanisms in relapse to cocaine-seeking behavior. Implications for
      medications development.

PMID- 10911941
TI  - 18-Methoxycoronaridine differentially alters the sensitized behavioral and
      dopaminergic responses to repeated cocaine and morphine administration.
      Implications for sensitization in the mediation of drug addiction.

PMID- 10911942
TI  - Some new directions for research on the biology of aging.
AB  - A highly selective, eclectic, and personal view of new directions and new
      opportunities for research on the biology of aging is briefly outlined. Some
      concern is raised regarding the present emphasis on the use of centenarians for
      the definition of genetic loci responsible for unusually robust retention of
      structure and function. More progress is likely to be made were we to focus on
      the genetic basis for "elite" aging in middle-aged subjects examined for very
      specific phenotypes, as these are likely to be far less polygenic. Descriptive
      gerontology is entering a renaissance, given such new clinical tools as
      functional MRI and basic science tools such as functional genomics and
      proteomics. Advances in genomics should expedite answers to such questions as why
      some avian species have exceptionally long lifespans despite unusual loads of
      oxidative stress. One hopes to see renewed mechanistic studies, using such tools,
      at the systems levels. New methodologies are permitting the evaluation of
      stochastic alterations in gene structure and function in postreplicative cells.
      The exciting work on molecular misreading should prompt us to reexplore the Orgel
      hypothesis as it applies to such cell types. Epigenetic shifts in gene expression
      that occur in association with sexual maturation and the cessation of growth may
      have deleterious consequences late in the life course. It will therefore be
      important for gerontologists to investigate the molecular biology of pubescence.
      Finally, our community should investigate the impact of environmental
      "gerontogens," agents that accelerate specific processes of aging and specific
      senescent phenotypes.

PMID- 10911943
TI  - Molecular gerontology. Bridging the simple and the complex.
AB  - It is clear, both empirically and theoretically, that the mechanisms of aging are
      multiple and complex. Nevertheless, single gene mutations and simple
      interventions such as calorie restriction have broad effects on the senescent
      phenotype. The major challenge is to unite highly reductionist analysis of
      molecular components with integrative model systems that can "put it all
      together." Two themes are developed. In the first, biochemical models are
      described that show how the network concept of cellular aging can be used to
      integrate multiple biochemical mechanisms that contribute to cellular
      instability. In the second theme, the role of intrinsic developmental chance is
      examined as a major factor contributing, in addition to genes and environment, to
      the divergence of the senescent phenotype. The implications of these themes for
      research strategies in molecular gerontology are discussed.

PMID- 10911944
TI  - Metabolic control and gene dysregulation in yeast aging.
AB  - Life span in the yeast Saccharomyces cerevisiae is usually measured by the number
      of divisions individual cells complete. Four broad physiologic processes that
      determine yeast life span have been identified: metabolic control, resistance to
      stress, chromatin-dependent gene regulation, and genetic stability. A pathway of
      interorganelle communication involving mitochondria, the nucleus, and peroxisomes
      has provided a molecular mechanism of aging based on metabolic control. This
      pathway functions continuously, rather than as an on-off switch, in determining
      life span. The longevity gene RAS2 modulates this pathway. RAS2 also modulates a
      variety of other cellular processes, including stress responses and chromatin
      dependent gene regulation. An optimal level of Ras2p activity is required for
      maximum longevity. This may be due to the integration of life maintenance
      processes by RAS2, which functions as a homeostatic device in yeast longevity.
      Loss of transcriptional silencing of heterochromatic regions of the genome is a
      mark of yeast aging. It is now clear that the functional status of chromatin
      plays an important role in aging. Changes in this functional status result in
      gene dysregulation, which can be altered by manipulation of the histone
      deacetylase genes. Silencing of ribosomal DNA appears to be of particular
      importance. Extrachromosomal ribosomal DNA circles are neither sufficient nor
      necessary for yeast aging.

PMID- 10911945
TI  - Mitochondrial oxidative stress and aging in the filamentous fungus Podospora
      anserina.
AB  - In the filamentous fungus Podospora anserina, mitochondrial oxidative stress is a
      major contributor to aging. Reactive oxygen species (ROS) generated as a result
      of electron leakage during respiration lead to damage of components of the
      electron transport chain. In aging wild-type cultures, damaged proteins cannot be
      replaced because the mitochondrial genes encoding some of the corresponding
      subunits gradually become deleted from the mitochondrial DNA (mtDNA).
      Consequently, these defects result in an increased generation of reactive oxygen
      species and respiration deficits leading to cell death. Analyses of wild-type
      strains and of different long-lived mutants of P. anserina provide strong
      evidence that molecular mechanisms controlling aging processes in this fungus are
      complex and act at different levels. A basic mechanism (e.g., damage by ROS)
      appears to be overlaid by prominent instabilities of the mtDNA.

PMID- 10911946
TI  - Molecular genetic mechanisms of life span manipulation in Caenorhabditis elegans.
AB  - Aging and a limited life span are fundamental biological realities. Recent
      studies have demonstrated that longevity can be manipulated and have revealed
      molecular mechanisms underlying longevity control in the soil nematode
      Caenorhabditis elegans. Signals from both neurons and the gonad appear to
      negatively regulate longevity. One tissue-specific signal involves an insulin
      like phosphatidylinositol 3-OH kinase pathway, dependent upon the DAF-16 forkhead
      transcription factor. These signals regulate mechanisms determining longevity
      that include the OLD-1 (formerly referred to as TKR-1) receptor tyrosine kinase.
      Interestingly, increased resistance to environmental stress shows a strong
      correlation with life extension.

PMID- 10911947
TI  - Genetics of human aging. The search for genes contributing to human longevity and
      diseases of the old.
AB  - An aging population of humans reflects early-onset morbidity and mortality as
      well as late-onset disease in the phase when the mortality rate doubles and,
      finally, longevity of extremely long-lived subjects. Genetic influences have been
      reported to be relevant for each of these three phases. A growing field in
      genetic research is aimed at the identification of genes involved in
      multifactorial diseases of the old and in longevity. Important issues in these
      studies include the definition of phenotype, which maximally highlights the
      genetic contribution, whether earlier and later onset phenotypes have loci in
      common, and how to rank or reject the many candidate disease loci found in
      different studies. These issues will be illustrated from research on
      cardiovascular disease and osteoarthritis.

PMID- 10911948
TI  - Genetics of survival.
AB  - The fields of gerontology and genetics have merged, spawning novel lines of
      investigation and generating a wealth of new results in recent years. However,
      the lack of clarity and consistency in the basic definitions upon which the
      science of gerontology must rest has fostered a certain amount of enduring
      confusion. Among the unclear issues are the genetic components of life span and
      the distinction between "normal" and "pathologic" aging. At a time of massive
      world population aging, such issues have, beyond their scientific importance, a
      momentous social and economic impact. A simple axiomatic framework, consisting of
      three definitions and five axioms, is proposed that clarifies the aforementioned
      issues and reconciles disparate data in gerontology. Based on this framework, a
      new classification of genes involved in survival is proposed. Within the
      Compensatory Adaptation Theory of aging, apparent paradoxes are solved and
      problems in gerontology may be formulated anew.

PMID- 10911949
TI  - Melanin accumulation accelerates melanocyte senescence by a mechanism involving
      p16INK4a/CDK4/pRB and E2F1.
AB  - Cellular and molecular evidence suggests that senescence is a powerful tumor
      suppressor mechanism that prevents most higher eukaryotic cells from dividing
      indefinitely in vivo. Recent work has demonstrated that alpha-melanocyte
      stimulating hormone (alpha-MSH) or cholera toxin (CT) can activate a cAMP pathway
      that elicits proliferative arrest and senescence in normal human pigmented
      melanocytes. In these cells, senescence is associated with increased binding of
      p16INK4a to CDK4 and loss of E2F-binding activity. Because senescence may provide
      defense against malignant transformation of melanocytes, and because pigmentation
      is a strong defense against melanoma, we examined the ability of melanocytes
      derived from light and dark skin to respond to CT. Here we demonstrate that in
      melanocytes derived from dark-skinned individuals, CT-induced melanogenesis is
      associated with accumulation of the tumor suppressor p16INK4a,
      underphosphorylated retinoblastoma protein (pRb), downregulation of cyclin E,
      decreased expression of E2F1, and loss of E2F-regulated S-phase gene expression.
      In contrast to other senescent cell types, melanocytes have reduced or absent
      levels of the cyclin-dependent kinase inhibitors p27Kip1 and p21Waf-1.
      Importantly, melanocytes derived from light-skinned individuals accumulated
      smaller amounts of melanin than did those from dark-skinned individuals under the
      same conditions, and they continued to proliferate for several more division
      cycles. This delayed senescence may result from reduced association of p16 with
      CDK4, reduced levels of underphosphorylated pRb, and steady levels of cyclin E
      and E2F1. Because cyclin E-CDK2 inhibition is required for p16-mediated growth
      suppression, upregulation of p16 and downregulation of cyclin E appear essential
      for maintenance of terminal growth and senescence. Given the rising incidence of
      melanoma, identification of major growth regulatory proteins involved in
      senescence should shed light on the biology of this genetically mysterious tumor.

PMID- 10911950
TI  - Stress-induced premature senescence. Essence of life, evolution, stress, and
      aging.

PMID- 10911951
TI  - Role of oxidative stress in telomere length regulation and replicative
      senescence.
AB  - Replicative senescence is tied into organismal aging processes in more than one
      respect, and telomeres appear to be the major trigger of replicative senescence
      under many conditions in vitro and in vivo. However, the structure-function
      relationships in telomeres, the mechanisms of telomere shortening with advancing
      replicative age, and the regulation of senescence by telomeres are far from
      understood. Combining recent data on telomere structure, function of telomere
      binding proteins, and sensitivity of telomeres to oxidative damage, an
      integrative model of telomere shortening and signaling is developed. The model
      suggests that t-loop formation hinders access of repair proteins to telomeres,
      leading to accumulation of a basic sites and single-strand breaks. These might
      contribute to accelerated telomere shortening by transient stalling of
      replication as well as, if present in high concentrations, to a relief of
      torsional tension which might destabilize the telomeric loop structure. As a
      result, the single-stranded G-rich overhang, which is present at the very ends of
      telomeres but is normally protected at the base of the telomeric loop, will be
      exposed to the nucleoplasm. Free G-rich telomeric single strands are a strong
      inductor of the p53 pathway, and exposure of the overhangs seems to be the first
      step in the signal transduction cascade to replicative senescence.

PMID- 10911952
TI  - Replicative senescence and oxidant-induced premature senescence. Beyond the
      control of cell cycle checkpoints.
AB  - Normal human diploid fibroblasts (HDFs) undergo replicative senescence inevitably
      in tissue culture after a certain number of cell divisions. A number of molecular
      changes observed in replicative senescent cells occur in somatic cells during the
      process of aging. Genetic studies on replicative senescence indicate the control
      of tumor suppression mechanisms. Despite the significance of replicative
      senescence in aging and cancer, little is known about the central cause of the
      complex changes observed in replicative senescent cells. The interest in the
      phenomenon has intensified in recent years, since damaging agents, certain
      oncogenes and tumor suppressor genes have been found to induce features of
      senescence in early passage young HDFs or in immortalized tumor cells. The
      reported features of senescence are summarized here in order to clarify the
      concept of replicative senescence or premature senescence. The experimental
      results of extending the replicative life span by reducing ambient oxygen tension
      or by N-tert-butyl-alpha-phenylnitrone (PBN) argue a role of oxidative damage in
      replicative senescence. By inducing premature senescence with a pulse treatment
      of H2O2, we can study the role of the cell cycle checkpoint proteins p53, p21,
      p16 and Rb in gaining each feature of senescence. Although p53 and Rb control G1
      arrest and Rb appears to control cell enlargement, activation of the senescent
      associate beta-galactosidase, loss of cell replication and multiple molecular
      changes observed in premature senescent or replicative senescent cells are likely
      controlled by mechanisms beyond the cell cycle checkpoints.

PMID- 10911953
TI  - Poly(ADP-ribosyl)ation, genomic instability, and longevity.
AB  - Poly(ADP-ribosyl)ation is a DNA strandbreak-driven posttranslational modification
      of nuclear proteins that is catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1),
      with NAD+ serving as substrate. Recently, additional PARP isoforms were described
      that seem to account for a minor fraction of cellular poly(ADP-ribose) synthesis.
      We have previously described a correlation between poly(ADP-ribosyl)ation
      capacity of mononuclear leukocytes of various mammalian species and species
      specific life span. Likewise, lymphoblastoid cell lines derived from human
      centenarians display a higher poly(ADP-ribosyl)ation capacity than do controls.
      At the functional level, recent data show that PARP-1 is a key regulator of
      alkylation-induced sister-chromatid exchange, imposing a negative control
      commensurate with the enzyme activity. PARP-1 activity may therefore be
      responsible for tuning the rate of genomic instability events that are provoked
      by the constant attack of endogenous and exogenous genotoxins to a level
      appropriate for the longevity potential of a given organism or species.

PMID- 10911954
TI  - Aging and longevity. A paradigm of complementation between homeostatic mechanisms
      and genetic control?
AB  - Aging is a universal and inevitable phenomenon that affects nearly all animal
      species. It can be considered the product of an interaction between genetic,
      environmental, and lifestyle factors, which in turn influence longevity that
      varies between and within species. It has been proposed not only that the aging
      process is under genetic control, but that it can also be considered a result of
      the failure of homeostasis due to the accumulation of damage. This review article
      discusses these issues, focusing on the function of genes that associate with
      aging and longevity, as well as on the molecular mechanisms that control cell
      survival and maintenance during aging.

PMID- 10911955
TI  - Protein degradation by the proteasome and its implications in aging.
AB  - Free radical damage to cellular components is believed to contribute to the aging
      process. Studies on proteins have shown both an age-related decline in several
      enzyme activities and an age-related accumulation of oxidized forms of protein.
      Oxidized forms of protein are generally degraded more rapidly than their native
      counterparts. Indeed, the normal functions of the cell involve the regular
      elimination of these altered molecules. The proteasome, a multienzymatic
      proteolytic complex, is the major enzymatic system in charge of cellular
      "cleansing" and plays a key role in the degradation of damaged proteins.
      Consequently, proteasome function is very important in controlling the level of
      altered proteins in eukaryotic cells. Because the steady-state level of oxidized
      protein reflects the balance between the rate of protein oxidation and the rate
      of protein degradation, age-related accumulation of altered protein can be due to
      an increase of free radical-mediated damage, a loss of protease activity, or the
      combination of both mechanisms. One of the hypotheses put forward to explain the
      accumulation of altered proteins is the decrease of proteasome activity with age.
      In this paper, the importance of oxidative damage to proteins and that of their
      elimination by the proteasome are first described. Then, evidence for a decline
      of proteasome activity upon aging and upon oxidative stress is provided by
      studies from our and other laboratories.

PMID- 10911956
TI  - Fibroblast responses to exogenous and autocrine growth factors relevant to tissue
      repair. The effect of aging.
AB  - The aging process is often associated with impaired wound healing, but the
      cellular and molecular mechanisms implicated are not completely understood.
      Accordingly, we have investigated the response of human fibroblasts from donors
      of various ages to platelet-derived and autocrine growth factors, in terms of
      mitogenicity as well as extracellular matrix synthesis and degradation. Our data
      indicate that fibroblast responses persist during aging, suggesting the
      involvement of systemic factors in the regulation of the healing process. In this
      context, we have found that neutral endopeptidase-24.11, a metalloproteinase
      controlling the action of neuroendocrine peptides and also of immunocyte
      chemotaxis, is overexpressed during aging. Finally, the connection between these
      data and those from in vitro aging studies is discussed.

PMID- 10911957
TI  - The Werner syndrome. A model for the study of human aging.
AB  - Human aging is a complex process that leads to the gradual deterioration of body
      functions with time. Various models to approach the study of aging have been
      launched over the years such as the genetic analysis of life span in the yeast S.
      cerevisiae, the worm C. elegans, the fruitfly, and mouse, among others. In human
      models, there have been extensive efforts using replicative senescence, the study
      of centenerians, comparisons of young versus old at the organismal, cellular, and
      molecular levels, and the study of premature aging syndromes to understand the
      mechanisms leading to aging. One good model for studying human aging is a rare
      autosomal recessive disorder known as the Werner syndrome (WS), which is
      characterized by accelerated aging in vivo and in vitro. A genetic defect
      implicated in WS was mapped to the WRN locus. Mutations in this gene are believed
      to be associated, early in adulthood, with clinical symptoms normally found in
      old individuals. WRN functions as a DNA helicase, and recent evidence, summarized
      in this review, suggests specific biochemical roles for this multifaceted
      protein. The interaction of WRN protein with RPA (replication protein A) and p53
      will undoubtedly direct efforts to further dissect the genetic pathway(s) in
      which WRN protein functions in DNA metabolism and will help to unravel its
      contribution to the human aging process.

PMID- 10911958
TI  - Calorie restriction and age-related oxidative stress.
AB  - Calorie restriction (CR) in mammals has been recognized as the best characterized
      and most reproducible strategy for extending maximum survival, retarding
      physiological aging, and delaying the onset of age-related pathologic conditions
      in mammals. The overwhelming majority of studies using CR have used short-lived
      rodent species, although current work using rhesus and squirrel monkeys will
      determine whether this paradigm is also relevant to manipulating the rate of
      primate aging. The mechanism by which restricted calorie intake modifies the rate
      of aging and pathology has been the subject of much controversy, although an
      attenuation in the lifetime accumulation of oxidative damage appears to be a
      central feature. Although the majority of studies have focused on the ability of
      cells from calorie-restricted animals to scavenge free radicals to explain the
      slower accrual of oxidative damage with age, it is not established that CR has a
      consistent effect to upregulate the activity of these enzymes in all tissues. A
      major effect of calorie-restricted feeding now appears to be on the rate of
      production or leak of free radicals from the mitochondria. The details of the
      adaptation and the signaling pathway that induces this effect are currently
      unknown.

PMID- 10911959
TI  - Role of mitochondrial DNA mutations in disease and aging.
AB  - Since Harman in 1972 first proposed a role in the process of aging for the
      mitochondrial genome, a wealth of evidence has been accumulated to support this
      theory. We discuss the hereditary mitochondrial DNA disorders, which we believe
      may give insight into both normal aging and neurodegenerative conditions. We then
      review the evidence for the role of mitochondrial DNA mutations in both aging and
      age-related disorders and also discuss new approaches for investigating the
      mitochondrial genome at a single cell level, by observing the activity of the
      mitochondrial enzyme cytochrome c oxidase.

PMID- 10911960
TI  - Inherited variability of the mitochondrial genome and successful aging in humans.
AB  - Increasing data indicate that polymorphic variants of nuclear loci can affect
      rate and quality of aging in humans. However, the mitochondrial genome is another
      good candidate, because of the central role played by mitochondrial genes in
      oxidative phosphorylation (OXPHOS) and cell metabolism. A characteristic of the
      mitochondrial genome (mtDNA) is the high level of interindividual variability
      that ensues from high mutation rate and unilinear inheritance. Related groups of
      germline/inherited mtDNA polymorphisms (haplogroups) have been identified as
      continent-specific sets of stable/ancient/associated restriction fragment length
      polymorphisms in the mtDNA coding region, representing markers capable of exactly
      depicting the mtDNA pool of a specific population. The hypothesis can be put
      forward that mtDNA variants included in a haplogroup may have similar OXPHOS
      efficiency and therefore act as genetic factors predisposing to individual
      successful or unsuccessful aging. This idea can be explored by sampling groups of
      individuals of different ages from a well-defined population and comparing the
      pools of mtDNA haplogroups between samples. The results obtained by screening
      mtDNA haplogroups in about 800 Italians of different ages, including more than
      200 centenarians, agree with the hypothesis that the inherited variability of the
      mitochondrial genome is associated with the chance of successful aging and
      longevity in humans.

PMID- 10911961
TI  - Mitochondrial oxidative stress. Physiologic consequences and potential for a role
      in aging.
AB  - During the last 10 years, the theory known as the "free radical theory of aging"
      has achieved prominence as one of the most compelling explanations for many of
      the degenerative changes associated with aging. Although its appeal derives from
      a long-standing body of supporting correlative data, the theory was only recently
      more rigorously tested. Ongoing researches in the study of free radical
      biochemistry and the genetics of aging have been at the forefront of this work.
      First, transgenic approaches in invertebrate models with candidate genes such as
      superoxide dismutase (SOD) involved in the detoxification of reactive oxygen
      species (ROS) have shown that the endogenous production of ROS due to normal
      physiologic processes is a major limiter of life span. Genes involved in ROS
      detoxification are highly conserved among eukaryotes; hence, the physiologic
      processes that limit life span in invertebrates are likely to be similar in
      higher eukaryotes. Secondly, transgenic mice deficient in the antioxidant enzyme
      mitochondrial superoxide dismutase (SOD2) die within their first week of life,
      demonstrating the importance of limiting endogenous mitochondrial free radicals
      in mammals. Together, data from studies using transgenic invertebrates and those
      using sod2 mutant mice demonstrate that modulation of metabolic ROS can have a
      profound effect on life span. We show here that the effects of mitochondrial ROS
      can be modulated through appropriate catalytic antioxidant intervention. These
      catalytic antioxidants are discussed in the context of mitochondrial oxidative
      stress and their potential role in intervening in mitochondrial oxidative stress
      and aging.

PMID- 10911962
TI  - Tissue mitochondrial DNA changes. A stochastic system.
AB  - Several lines of evidence support the view that the bioenergetic function of the
      mitochondria in postmitotic tissue deteriorates during normal aging. Skeletal
      muscle is one such tissue that undergoes age-related fiber loss and atrophy and
      an age-associated rise in the number of cytochrome c oxidase (COX) deficient
      fibers. With such metabolic pressure placed on skeletal muscle it would be an
      obvious advantage to supplement the cellular requirement for energy by up
      regulating glycolysis, and alternative pathway for energy synthesis. Analysis of
      rat skeletal muscle utilizing antibodies directed against key enzymes involved in
      glycolysis has provided evidence of an age-associated increase in the enzymes
      involved in glycolysis. Fructose-6-phosphate kinase, aldolase, glyceraldehyde-3
      phosphate dehydrogenase, and pyruvate kinase protein levels appeared to increase
      in the soleus, gracilis, and quadriceps muscle from aged rats. The increase in
      the level of these proteins appeared to correlate to a corresponding decrease in
      the amount of cytochrome c oxidase protein measured in the same tissue. Together
      these results are interpreted to represent a general upregulation of glycolysis
      that occurs in response to the age-associated decrease in mitochondrial energy
      capacity. Mitochondrial DNA (mtDNA) damage and mutations may accumulate with
      advancing age until they reach a threshold level were they impinge on the
      bioenergy capacity of the cell or tissue. Evidence indicates that mtDNA from the
      skeletal muscle of both aged rats and humans not only undergoes changes at the
      nucleotide sequence level (mutations and DNA damage), but also undergoes
      modifications at the tertiary level to generate unique age-related conformational
      mtDNA species. One particular age-related conformational form was only detected
      in aged rat tissues with high demands on respiration, specifically in heart,
      kidney, soleus muscle, and, to a lesser extent, the quadriceps muscle. The age
      related form was not detected in gracilis muscle which is predominantly dependent
      upon glycolysis with regard to its energy requirements. Finally, a comprehensive
      hypothesis is presented that features the stochastic nature of the mitochondrial
      system. The basis of the hypothesis is that a dynamic relationship exists between
      endogenous mutagen production, DNA repair, mtDNA turnover, and nuclear control of
      mtDNA copy number and that age-associated changes in the dynamics of this
      relationship lead to a loss of functional full-length mtDNA that eventually leads
      to bioenergy decline.

PMID- 10911963
TI  - Inflamm-aging. An evolutionary perspective on immunosenescence.
AB  - In this paper we extend the "network theory of aging," and we argue that a global
      reduction in the capacity to cope with a variety of stressors and a concomitant
      progressive increase in proinflammatory status are major characteristics of the
      aging process. This phenomenon, which we will refer to as "inflamm-aging," is
      provoked by a continuous antigenic load and stress. On the basis of evolutionary
      studies, we also argue that the immune and the stress responses are equivalent
      and that antigens are nothing other than particular types of stressors. We also
      propose to return macrophage to its rightful place as central actor not only in
      the inflammatory response and immunity, but also in the stress response. The rate
      of reaching the threshold of proinflammatory status over which
      diseases/disabilities ensue and the individual capacity to cope with and adapt to
      stressors are assumed to be complex traits with a genetic component. Finally, we
      argue that the persistence of inflammatory stimuli over time represents the
      biologic background (first hit) favoring the susceptibility to age-related
      diseases/disabilities. A second hit (absence of robust gene variants and/or
      presence of frail gene variants) is likely necessary to develop overt organ
      specific age-related diseases having an inflammatory pathogenesis, such as
      atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this
      perspective, several paradoxes of healthy centenarians (increase of plasma levels
      of inflammatory cytokines, acute phase proteins, and coagulation factors) are
      illustrated and explained. In conclusion, the beneficial effects of inflammation
      devoted to the neutralization of dangerous/harmful agents early in life and in
      adulthood become detrimental late in life in a period largely not foreseen by
      evolution, according to the antagonistic pleiotropy theory of aging.

PMID- 10911964
TI  - The CA1 region of the human hippocampus is a hot spot in Alzheimer's disease.
AB  - Data from an ongoing study of differences in the total number of neurons in the
      five major subdivisions of the hippocampal regions of the brains of patients with
      Alzheimer's disease (AD) and normal age-matched controls confirm an earlier
      finding from our laboratories of a pronounced loss of CA1 neurons associated with
      AD. In view of an earlier finding that the CA1 region does not suffer normal age
      related neuronal loss, these data support the earlier conclusion that the
      neuropathologic mechanisms involved in the AD-related losses in CA1 are not
      related to normal aging and that the study of the cellular and molecular events
      involved in the AD-related loss of CA1 cells can aid in the identification of the
      unique pathologic processes associated with AD.

PMID- 10911965
TI  - Transgenic mouse models of Alzheimer's disease.
AB  - Alzheimer's disease (AD) pathology is characterized by A beta peptide-containing
      plaques, neurofibrillary tangles consisting of hyperphosphorylated tau, extensive
      neuritic degeneration, and distinct neuron loss. We generated several transgenic
      mouse lines expressing the human amyloid precursor protein (APP751) containing
      the AD-linked KM670/671NL double mutation (Swedish mutation) under the control of
      a neuron-specific Thy-1 promoter fragment. In the best APP-expressing line
      (APP23), compact A beta deposits can be detected at 6 months of age. These
      plaques dramatically increase with age, are mostly Congo Red positive, and
      accumulate typical plaque-associated proteins such as heparansulfate proteoglycan
      and apolipoprotein E. Activated astrocytes and microglia indicative of
      inflammatory processes reminiscent of AD accumulate around the deposits.
      Furthermore, plaques are surrounded by enlarged dystrophic neurites as visualized
      by neurofilament or Holmes-Luxol staining. Strong staining for
      acetylcholinesterase activity is found throughout the plaques and is accompanied
      by local distortion of the cholinergic fiber network. All congophilic plaques
      contain hyperphosphorylated tau reminiscent of early tau pathology. Modern
      stereologic methods demonstrate a significant loss of neurons in the hippocampal
      CA1 region, correlating with an increasing A beta plaque load. Interestingly,
      APP23 mice develop cerebral amyloid angiopathy in addition to amyloid plaques
      even though the APP transgene is only expressed in neurons. Crossbreeding of
      APP23 mice with transgenic mice carrying AD-linked presenilin mutations but not
      wild-type presenilin resulted in enhanced formation of pathology. In conclusion,
      our APP transgenic mice present many pathologic features, similar to those
      observed in AD and therefore offer excellent tools for studying the contribution
      of A beta to AD pathogenesis.

PMID- 10911966
TI  - Molecular misreading. A new type of transcript mutation in gerontology.
AB  - Molecular misreading is a novel process that causes mutations in neuronal
      transcripts. It is defined as the inaccurate conversion of genomic information
      from DNA into nonsense transcripts and the subsequent translation into mutant
      proteins. As a result of dinucleotide deletions (delta GA, delta GU, delta CU) in
      and around GAGAG motifs in mRNA the reading frame shifts to the +1 frame, and
      subsequently the so-called +1 proteins are synthetized. +1 Proteins have a wild
      type NH2 terminus and from the site of the dinucleotide deletion onwards an
      aberrant, nonfunctional COOH terminus. Molecular misreading was found in the rat
      vasopressin gene associated with diabetes insipidus and in the human genes linked
      to Alzheimer's disease (AD), that is, beta-amyloid precursor protein (beta APP)
      and ubiquitin-B (UBB). Moreover, beta APP+1 and UBB+1 proteins accumulate in the
      neuropathological hallmarks of AD. Inasmuch as these +1 proteins were also found
      in elderly, nondemented control patients, but not in younger ones (< 72 years),
      molecular misreading may act as a factor that becomes manifest in aged people. A
      hotspot for dinucleotide deletions is GAGAG motifs. Because statistically an
      average of 2.1 GAGAG motifs per gene can be expected, other genes expressed in
      other tissues may undergo molecular misreading as well. Indeed, we recently
      detected +1 proteins in proliferating cells present in tissues such as the liver,
      epididymis, parotid gland, and neuroblastoma cell lines. Therefore, molecular
      misreading can be regarded as a general biological source of transcript errors
      that may be involved in cellular derangements in numerous age-related pathologic
      conditions apart from Alzheimer's disease.

PMID- 10911967
TI  - Biogerontology: the next step.
AB  - After a long period of collecting empirical data describing the changes in
      organisms, organs, tissues, cells, and macromolecules, biogerontological research
      is now able to develop various possibilities for intervention. Because aging is a
      stochastic and nondeterministic process characterized by a progressive failure of
      maintenance and repair, it is reasoned that gene involved in homeodynamic repair
      pathways are the most likely candidate gerontogenes. A promising approach for the
      identification of critical gerontogenic processes is through the hormesis-like
      positive effects of mild stress. Stimulation of various repair pathways by mild
      stress has significant effects on delaying the onset of various age-associated
      alterations in cells, tissues, and organisms.

PMID- 10911968
TI  - Nuclear-mitochondrial interactions involved in aging in Podospora anserina.

PMID- 10911969
TI  - Inherited frailty. ApoE alleles determine survival after a diagnosis of heart
      disease or stroke at ages 85+.

PMID- 10911970
TI  - MtDNA deletions in aging and in nonmitochondrial pathologies.

PMID- 10911971
TI  - Transcriptome and proteome analysis in human senescent fibroblasts and
      fibroblasts undergoing premature senescence induced by repeated sublethal
      stresses.

PMID- 10911972
TI  - Human diploid fibroblasts display a decreased level of c-fos mRNA at 72 hours
      after exposure to sublethal H2O2 stress.

PMID- 10911973
TI  - Replicative senescence of interleukin-2-dependent human T lymphocytes. Flow
      cytometric characteristics of phenotype changes.

PMID- 10911974
TI  - Age-related changes in irradiation-induced apoptosis and expression of p21 and
      p53 in crypt stem cells of murine intestine.

PMID- 10911975
TI  - Testing evolutionary theories of aging.

PMID- 10911976
TI  - A novel in vitro model of conditionally immortalized human vascular smooth muscle
      cells. A tool for aging studies.

PMID- 10911977
TI  - Using stress resistance to isolate novel longevity mutations in Caenorhabditis
      elegans.

PMID- 10911978
TI  - Telomere length as a marker of oxidative stress in primary human fibroblast
      cultures.

PMID- 10911979
TI  - Programmed cell death and senescence in skeletal muscle stem cells.

PMID- 10911980
TI  - Study of the H1 linker histone variant, H1o, during the in vitro aging of human
      diploid fibroblasts.

PMID- 10911981
TI  - Aging-related muscle dysfunction. Failure of adaptation to oxidative stress?

PMID- 10911982
TI  - A theoretical model for "in machina" experiments on immunosenescence.

PMID- 10911983
TI  - Chromium in the environment: an evaluation of exposure of the UK general
      population and possible adverse health effects.
AB  - Chromium in the hexavalent form, Cr(VI), has long been recognized as a carcinogen
      and there is concern as to the effects of continuous low-level exposure to
      chromium both occupationally and environmentally. This review summarizes the
      available exposure data and known health effects and evaluates the potential risk
      to human health in the United Kingdom. Chromium emissions to the environment in
      the United Kingdom are predominantly derived from fuel combustion, waste
      incineration, and industrial processes. The less toxic trivalent form of chromium
      [Cr(III)] is dominant in most environmental compartments, and any Cr(VI), the
      more toxic form, that is emitted to the environment can be reduced to Cr(III).
      Food is a major source of exposure to chromium, and estimated daily oral intakes
      for infants (1 yr), children (11 yr), and adults are 33-45, 123-171, and 246-343
      micrograms/person/d, respectively. Soil ingestion, particularly common in young
      children, can contribute to oral intake. Inhalation is a minor route of exposure
      for the general population. Average daily inhalation intakes in infants can range
      from 0.004 microgram/d for rural infants to 0.14 microgram/d for urban infants
      who are passively exposed to tobacco smoke, whereas adults who live in
      industrialized areas and smoke may take up between 2 and 12 micrograms/d. The
      most serious health effect associated with Cr(VI) is lung cancer, which has been
      associated with some occupational exposure scenarios, whereas Cr(III) is an
      essential nutrient with a broad safety range and low toxicity. The human body has
      effective detoxification mechanisms that can reduce ingested or inhaled Cr(VI) to
      Cr(III). In conclusion, there is no clear evidence to relate exposure to
      environmental levels of chromium with adverse health effects in either the
      general UK population or subgroups exposed to chromium around industrialized or
      contaminated sites. It can be expected that an improved understanding of the
      relevance of possible long-term accumulation of Cr(III) in the body may
      facilitate a more complete assessment, in the future, of the health risks in the
      general population associated with environmental exposure to chromium.

PMID- 10911984
TI  - The practice of exposure assessment: a state-of-the-art review.
AB  - Each of us encounters hundreds of toxic agents everyday, without exposure and
      subsequent absorption (uptake) however, there is no risk of injury. Thus,
      exposure assessment is one of the three legs of the stool (along with toxicity
      assessment and dose-response assessment) upon which the practice of risk
      assessment rests. The field of exposure assessment has evolved out of at least 3
      other disciplines over the past 50 years, including health physics, industrial
      hygiene, and epidemiology. Exposure assessments are a necessary component to
      understanding the hazard posed by exposure to naturally (e.g., aflatoxins in
      foods, radon in air) and nonnaturally occurring toxicants (e.g., benzene in
      groundwater, MTBE in air, and food additives). This article presents a thorough
      review of the field, including a discussion of the terminology used in exposure
      assessment, a description of how to quantitatively estimate dose for the major
      sources of exposure (food, water, air, and soil), and many of the best sources of
      information. In addition, techniques for assessing both variability and
      uncertainty are presented. Lessons learned over the past twenty years are
      emphasized. Some example calculations are included, nearly 400 references are
      cited, and a glossary of terms is provided.

PMID- 10911985
TI  - Synergistic coupling of histone H3 phosphorylation and acetylation in response to
      epidermal growth factor stimulation.
AB  - Histone acetylation and phosphorylation have separately been suggested to affect
      chromatin structure and gene expression. Here we report that these two
      modifications are synergistic. Stimulation of mammalian cells by epidermal growth
      factor (EGF) results in rapid and sequential phosphorylation and acetylation of
      H3, and these dimodified H3 molecules are preferentially associated with the EGF
      activated c-fos promoter in a MAP kinase-dependent manner. In addition, the
      prototypical histone acetyltransferase Gcn5 displays an up to 10-fold preference
      for phosphorylated (Ser-10) H3 over nonphosphorylated H3 as substrate in vitro,
      suggesting that H3 phosphorylation can affect the efficiency of subsequent
      acetylation reactions. Together, these results illustrate how the addition of
      multiple histone modifications may be coupled during the process of gene
      expression.

PMID- 10911986
TI  - Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in
      vivo to Gcn5-mediated acetylation at lysine 14.
AB  - Multiple covalent modifications exist in the amino-terminal tails of core
      histones, but whether a relationship exists between them is unknown. We examined
      the relationship between serine 10 phosphorylation and lysine 14 acetylation in
      histone H3 and have found that, in vitro, several HAT enzymes displayed increased
      activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10
      phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for
      arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the
      ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at
      a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same
      subset of genes was also impaired by substitution of serine 10 to alanine in the
      histone H3 tail. These observations suggest that transcriptional regulation
      occurs by multiple mechanistically linked covalent modifications of histones.

PMID- 10911987
TI  - Multiple links between the NuA4 histone acetyltransferase complex and epigenetic
      control of transcription.
AB  - NuA4 is an essential histone H4/H2A acetyltransferase complex that interacts with
      activators and stimulates transcription in vitro. We have identified three novel
      NuA4 subunits: Act3/Arp4, an actin-related protein implicated in epigenetic
      control of transcription, Act1, and Epl1, a protein homologous to Drosophila
      Enhancer of Polycomb. Act3/Arp4 binds nucleosomes in vitro and is required for
      NuA4 integrity in vivo. Mutations in ACT3 and acetyltransferase-encoding ESA1
      cause gene-specific transcription defects. Accordingly, NuA4 is localized in
      precise loci within the nucleus and does not overlap with the silent chromatin
      marker Sir3. These data along with the known epigenetic roles of Act3/Arp4 and
      homologs of Epl1 and Esa1 strongly support an essential role for chromatin
      structure modification by NuA4 in transcription regulation in vivo.

PMID- 10911988
TI  - The 26S proteasome is required for estrogen receptor-alpha and coactivator
      turnover and for efficient estrogen receptor-alpha transactivation.
AB  - Estrogen receptor-alpha (ER alpha) is downregulated in the presence of its
      cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here,
      we show that ubiquitin proteasome function is required for ER alpha to serve as a
      transcriptional activator. Deletion of the last 61 amino acids of ER alpha,
      including residues that form helix 12, abolishes ligand-mediated downregulation
      of the receptor as do point mutations in the ligand binding domain that impair
      coactivator binding. In addition, coactivators also are subject to degradation by
      the 26S proteasome, but their intrinsic transcriptional activity is not affected.
      These data provide evidence that protein interactions with ER alpha coactivator
      binding surfaces are important for ligand-mediated receptor down-regulation and
      suggest that receptor and coactivator turnover contributes to ER alpha
      transcriptional activity.

PMID- 10911989
TI  - Multisite RNA binding and release of polypyrimidine tract binding protein during
      the regulation of c-src neural-specific splicing.
AB  - We studied the role of polypyrimidine tract binding protein in repressing
      splicing of the c-src neuron-specific N1 exon. Immunodepletion/add-back
      experiments demonstrate that PTB is essential for splicing repression in HeLa
      extract. When splicing is repressed, PTB cross-links to intronic CUCUCU elements
      flanking the N1 exon. Mutation of the downstream CU elements causes dissociation
      of PTB from the intact upstream CU elements and allows splicing. Thus, PTB
      molecules bound to multiple elements cooperate to repress splicing.
      Interestingly, in neuronal WERI-1 cell extract where N1 is spliced, PTB also
      binds to the upstream CU elements but is dissociated in the presence of ATP. We
      conclude that splicing repression by PTB is modulated in different cells by a
      combination of cooperative binding and ATP-dependent dissociation.

PMID- 10911990
TI  - Myotonic dystrophy: the role of the CUG triplet repeats in splicing of a novel
      DMPK exon and altered cytoplasmic DMPK mRNA isoform ratios.
AB  - The mechanism by which (CTG)n expansion in the 3' UTR of the DMPK gene causes
      myotonic dystrophy (DM) is unknown. We identified four RNA splicing factors-
      hnRNP C, U2AF (U2 auxiliary factor), PTB (polypyrimidine tract binding protein),
      and PSF (PTB associated splicing factor)--that bind to two short regions 3' of
      the (CUG)n, and found a novel 3' DMPK exon resulting in an mRNA lacking the
      repeats. We propose that the (CUG)n is an essential cis acting element for this
      splicing event. In contrast to (CUG)n containing mRNAs, the novel isoform is not
      retained in the nucleus in DM cells, resulting in imbalances in relative levels
      of cytoplasmic DMPK mRNA isoforms and a new dominant effect of the mutation on
      DMPK.

PMID- 10911991
TI  - Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy
      similar to the human X-linked disorder incontinentia pigmenti.
AB  - IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK),
      encoded by an X-linked gene in mice and humans. It is required for NF-kappa B
      activation and resistance to TNF-induced apoptosis. Female mice heterozygous for
      Ikk gamma/Nemo deficiency develop a unique dermatopathy characterized by
      keratinocyte hyperproliferation, skin inflammation, hyperkeratosis, and increased
      apoptosis. Although Ikk gamma+/- females eventually recover, Ikk gamma- males die
      in utero. These symptoms and inheritance pattern are very similar to those of
      incontinentia pigmenti (IP), a human genodermatosis, synthenic with the IKK
      gamma/NEMO locus. Indeed, biopsies and cells from IP patients exhibit defective
      IKK gamma/NEMO expression but normal expression of IKK catalytic subunits. This
      unique self-limiting disease, the first to be genetically linked to the IKK
      signaling pathway, is dependent on X-chromosome inactivation. We propose that the
      IKK gamma/NEMO-deficient cells trigger an inflammatory reaction that eventually
      leads to their death.

PMID- 10911992
TI  - NEMO/IKK gamma-deficient mice model incontinentia pigmenti.
AB  - Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO)
      produces male embryonic lethality, completely blocks NF-kappa B activation by
      proinflammatory cytokines, and interferes with the generation and/or persistence
      of lymphocytes. Heterozygous female mice develop patchy skin lesions with massive
      granulocyte infiltration and hyperproliferation and increased apoptosis of
      keratinocytes. Diseased animals present severe growth retardation and early
      mortality. Surviving mice recover almost completely, presumably through clearing
      the skin of NEMO-deficient keratinocytes. Male lethality and strikingly similar
      skin lesions in heterozygous females are hallmarks of the human genetic disorder
      incontinentia pigmenti (IP). Together with the recent discovery that mutations in
      the human NEMO gene cause IP, our results indicate that we have created a mouse
      model for that disease.

PMID- 10911993
TI  - DNA ligase IV deficiency in mice leads to defective neurogenesis and embryonic
      lethality via the p53 pathway.
AB  - DNA ligase IV (LIG4) is a nonhomologous end-joining (NHEJ) protein used for V(D)J
      recombination and DNA repair. In mice, Lig4 deficiency causes embryonic
      lethality, massive neuronal apoptosis, arrested lymphogenesis, and various
      cellular defects. Herein, we assess potential roles in this phenotype for
      INK4a/ARF and p53, two proteins implicated in apoptosis and senescence. INK4a/ARF
      deficiency rescued proliferation/senescence defects of Lig4-deficient fibroblasts
      but not other phenotypic aspects. In contrast, p53 deficiency rescued embryonic
      lethality, neuronal apoptosis, and fibroblast proliferation/senescence defects
      but not lymphocyte development or radiosensitivity. Young Lig4/p53 double null
      mice routinely died from pro-B lymphomas. Thus, in the context of Lig4
      deficiency, embryonic lethality and neuronal apoptosis likely result from a p53
      dependent response to unrepaired DNA damage, and neuronal apoptosis and
      lymphocyte developmental defects can be mechanistically dissociated.

PMID- 10911994
TI  - FLS2: an LRR receptor-like kinase involved in the perception of the bacterial
      elicitor flagellin in Arabidopsis.
AB  - Flagellin, the main protein of the bacterial flagella, elicits defence responses
      and alters growth in Arabidopsis seedlings. Previously, we identified the FLS1
      locus, which confers flagellin insensitivity in Ws-0. To identify additional
      components involved in flagellin perception, we screened for flagellin
      insensitivity mutants in the flagellin-sensitive accession La-er. Here, we
      describe the identification of a new locus, FLS2, by a map-based strategy. The
      FLS2 gene is ubiquitously expressed and encodes a putative receptor kinase. FLS2
      shares structural and functional homologies with known plant resistance genes and
      with components involved in the innate immune system of mammals and insects.

PMID- 10911995
TI  - GTP hydrolysis by Ran is required for nuclear envelope assembly.
AB  - Nuclear formation in Xenopus egg extracts requires cytosol and is inhibited by
      GTP gamma S, indicating a requirement for GTPase activity. Nuclear envelope (NE)
      vesicle fusion is extensively inhibited by GTP gamma S and two mutant forms of
      the Ran GTPase, Q69L and T24N. Depletion of either Ran or RCC1, the exchange
      factor for Ran, from the assembly reaction also inhibits this step of NE
      formation. Ran depletion can be complemented by the addition of Ran loaded with
      either GTP or GDP but not with GTP gamma S. RCC1 depletion is only complemented
      by RCC1 itself or by RanGTP. Thus, generation of RanGTP by RCC1 and GTP
      hydrolysis by Ran are both required for the extensive membrane fusion events that
      lead to NE formation.

PMID- 10911996
TI  - Unexpected structural diversity in DNA recombination: the restriction
      endonuclease connection.
AB  - Transposition requires a coordinated series of DNA breakage and joining
      reactions. The Tn7 transposase contains two proteins: TnsA, which carries out DNA
      breakage at the 5' ends of the transposon, and TnsB, which carries out breakage
      and joining at the 3' ends of the transposon. TnsB is a member of the retroviral
      integrase superfamily whose hallmark is a conserved DDE motif. We report here the
      structure of TnsA at 2.4 A resolution. Surprisingly, the TnsA fold is that of a
      type II restriction endonuclease. Thus, Tn7 transposition involves a
      collaboration between polypeptides, one containing a DDE motif and one that does
      not. This result indicates that the range of biological processes that utilize
      restriction enzyme-like folds also includes DNA transposition.

PMID- 10911997
TI  - Catalytic mechanism of DNA topoisomerase IB.
AB  - Type IB topoisomerases and tyrosine recombinases are structurally homologous
      strand transferases that act through DNA-(3'-phosphotyrosyl)-enzyme
      intermediates. A constellation of conserved amino acids (Arg-130, Lys-167, Arg
      223, and His-265 in vaccinia topoisomerase) catalyzes transesterification of
      tyrosine to the scissile phosphodiester. We used 5'-bridging phosphorothiolate
      modified DNAs to implicate Lys-167 as a general acid catalyst. The lower pKa of
      the 5'-S leaving group versus 5'-O restored activity to the K167A mutant, whereas
      there was no positive thio effect for mutants R223A and H265A. The lysine is
      located atop a flexible hairpin loop, and it shifts into the minor groove upon
      DNA binding. Coupling of conformational changes in a general acid loop to
      covalent catalysis of phosphoryl transfer is one of several mechanistic features
      shared by the topoisomerase/recombinase and protein phosphatase superfamilies.

PMID- 10911998
TI  - Structural basis for specificity switching of the Src SH2 domain.
AB  - The Src SH2 domain binds pYEEI-containing phosphopeptides in an extended
      conformation with a hydrophobic pocket, which includes ThrEF1, binding Ile(pY
      +3). Mutating ThrEF1 to tryptophan switches specificity to an Asn(pY +2)
      requirement, yielding a biological mimic of the Grb2 SH2 domain. Here we show
      that the Src ThrEF1Trp SH2 domain mutant binds pYVNV phosphopeptides in a beta
      turn conformation, which, despite differing conformations of the interacting
      tryptophan, closely resembles the native Grb2/pYVNV cognate peptide binding mode.
      The ThrEF1Trp substitution therefore switches specificity by physically occluding
      the pTyr +3 binding pocket and by providing additional interaction surface area
      for Asn(pY +2). This demonstrates structurally how novel SH2 domain specificities
      may rapidly evolve through single amino acid substitutions and suggests how new
      signaling pathways may develop.

PMID- 10911999
TI  - Solution structure of N-TRADD and characterization of the interaction of N-TRADD
      and C-TRAF2, a key step in the TNFR1 signaling pathway.
AB  - TRADD is a multifunctional signaling adaptor protein that is recruited to TNFR1
      upon ligand binding. The C-terminal of TRADD comprises the "death domain" that is
      responsible for association of TNFR1 and other death domain-containing proteins
      such as FADD and RIP. The N-terminal domain (N-TRADD) promotes the recruitment of
      TRAF2 to TNFR1 by binding to the C-terminal of TRAF2, leading to the activation
      of JNK/AP1 and NF-kappa B. The solution structure of N-TRADD was determined,
      revealing a novel protein fold. A combination of NMR, BIAcore, and mutagenesis
      experiments was used to help identify the site of interaction of N-TRADD with C
      TRAF2, providing a framework for future attempts to selectively inhibit the TNF
      signaling pathways.

PMID- 10912000
TI  - Uracil-DNA glycosylase (UNG)-deficient mice reveal a primary role of the enzyme
      during DNA replication.
AB  - Gene-targeted knockout mice have been generated lacking the major uracil-DNA
      glycosylase, UNG. In contrast to ung- mutants of bacteria and yeast, such mice do
      not exhibit a greatly increased spontaneous mutation frequency. However, there is
      only slow removal of uracil from misincorporated dUMP in isolated ung-/- nuclei
      and an elevated steady-state level of uracil in DNA in dividing ung-/- cells. A
      backup uracil-excising activity in tissue extracts from ung null mice, with
      properties indistinguishable from the mammalian SMUG1 DNA glycosylase, may
      account for the repair of premutagenic U:G mispairs resulting from cytosine
      deamination in vivo. The nuclear UNG protein has apparently evolved a specialized
      role in mammalian cells counteracting U:A base pairs formed by use of dUTP during
      DNA synthesis.

PMID- 10912001
TI  - FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation and
      reveals functional differences between P-TEFb and TFIIH.
AB  - We report that the chromatin-specific transcription elongation factor FACT
      functions in conjunction with the RNA polymerase II CTD kinase P-TEFb to
      alleviate transcription inhibition by DSIF (DRB sensitivity-inducing factor) and
      NELF (negative elongation factor). We find that the kinase activity of TFIIH is
      dispensable for this activity, demonstrating that TFIIH-mediated CTD
      phosphorylation is not involved in the regulation of FACT and DSIF/NELF
      activities. Thus, we propose a novel transcriptional regulatory network in which
      DSIF/NELF inhibition of transcription is prevented by P-TEFb in cooperation with
      FACT. This study uncovers a novel role for FACT in the regulation of
      transcription on naked DNA that is independent of its activities on chromatin
      templates. In addition, this study reveals functional differences between P-TEFb
      and TFIIH in the regulation of transcription.

PMID- 10912002
TI  - [Nonspecific defense mechanisms].

PMID- 10912003
TI  - [Natural history of pneumopathy].

PMID- 10912004
TI  - [Risk factors and prognosis].

PMID- 10912005
TI  - [Clinical and radiological aspects: conclusions, synthesis and prospects].

PMID- 10912006
TI  - [Management by the general practitioner].

PMID- 10912007
TI  - [Management in the acute phase].

PMID- 10912008
TI  - [Global management from the viewpoint of returning home].

PMID- 10912009
TI  - [Decisional approach. The patient: conclusions, synthesis and prospects].

PMID- 10912010
TI  - [Immunologic aging].

PMID- 10912011
TI  - [Microbiology].

PMID- 10912012
TI  - [Antibiotic therapy: pharmacology and therapeutic aspects].

PMID- 10912013
TI  - [Decisional approach. The illness: conclusions, synthesis and prospects].

PMID- 10912014
TI  - [The use of fibrin glue in abdominal surgery].
AB  - The data on use of fibrin glue (FG) in 215 patients operated on the abdominal
      organs, employing laser surgical techniques, are presented. In 132 patients, the
      complicated forms of gastric and duodenal ulcer disease, in 25--gastric cancer,
      in 24--colonic tumors, in 26--injuries to the liver were revealed. Considerable
      reduction in incidence of early postoperative complications as compared with that
      in patients operated on with the use of conventional techniques was noted.

PMID- 10912015
TI  - [A treatment method for patients with a local suppurative infection].
AB  - To treat patients with the post-injection abscess and mastitis, suspension of
      alveolar porcine macrophages was periodically introduced via a drainage tube into
      the cavity formed after sparing opening of an abscess and removal of necrotic
      tissues. Local use of the substance permitted to shorten by 30-50% the duration
      of hospital stay of the patients as compared to that in use of conventional
      methods.

PMID- 10912017
TI  - [The use of lasers in treating soft-tissue suppurative-inflammatory diseases].
AB  - The authors have established in vitro, that helium-neon (HN) laser rays at the
      therapeutic doses had no bactericidal effect. Bactericidal effect of the rays of
      an ultraviolet (UV) laser is manifested in exposure for 5 min (output power of 3
      mW, pulse frequency of 100 Hz, diameter of the irradiated area of 3 mm). In the
      clinic, a combined method with the use of HN-laser with radiant power of 20 J/cm2
      and UV laser with radiant power of 7 J/cm2 was employed. Duration of treatment of
      purulent-inflammatory diseases reduced 2-5-fold as compared with that in use of
      conventional methods of treatment.

PMID- 10912016
TI  - [A comparative study of the efficacy of antiseptics used for preventing
      infectious complications].
AB  - The results of comparative study of antimicrobial properties of decamethoxine and
      chlorhexidine bigluconate are presented. It is established that resistant to
      antibiotics strains of pathogens of nosocomial infections were highly susceptible
      to decamethoxine. Decamethoxine and, to a lesser degree, chlorhexidine
      bigluconate have a bactericidal effect in treatment of hand skin of the medical
      staff of surgical department. The authors consider it expedient to use the
      mentioned preparations for prevention of nosocomial infection.

PMID- 10912018
TI  - [The use of the catalase P-47 preparation for treating long-term nonhealing
      wounds and trophic ulcers].
AB  - The experience with the use of P-47 catalase preparation for treatment of 155
      patients with sluggish wounds and ulcers is summarized. Use of P-47 preparation
      contributes to increase in catalase activity and hence to normalization of the
      course of regenerative processes. P-47 preparation is recommended as an effective
      means for treatment of sluggish wounds and ulcers.

PMID- 10912019
TI  - [An experimental and clinical validation for the use of a collagen sponge for
      treating the suppurative-inflammatory complications of wound healing in emergency
      abdominal surgery].
AB  - In use of a collagen sponge in 253 patients with purulent inflammatory
      complications after appendectomy, a wound is cleaned 10 days, and
      epithelialization of its edges occurs 7.6 days earlier as compared to the control
      group patients. Duration of hospital stay of the patients reduces by 11.4 days.

PMID- 10912020
TI  - [A regenerative method for the surgical treatment of paronychia by applying a
      buried suture].
AB  - The suggested regenerative method for surgical treatment of panaritium with
      placing a blind suture at the period of formation of lipoblasts (at day 3 after
      the operative intervention) permits to prevent development of purulent
      complications, accelerate the process of wound healing within a period
      approximating that in wound healing by primary intention with complete
      restoration of the hand and digit function.

PMID- 10912021
TI  - [The skin microflora of the upper extremities as the source of suppurative
      diseases of the hand and fingers].
AB  - The parallel bacteriologic studies of microflora of skin of the upper extremities
      and pus in purulent diseases of the hands and digits in workers of the combine
      plant was carried out. It was established that besides Staphylococcus aureus, the
      haemolytic forms of coagulase-negative species, in particular S. hyicus, S.
      epidermidis, S. haemolyticus, S. warneri, were the agents of purulent
      inflammatory processes both in monocultures and in associations. Incidence of
      isolation of staphylococci and density of bacterial populations depend on the use
      of oils and emulsions in the manufacturing process.

PMID- 10912022
TI  - [The use of a laser in the surgical treatment of an epithelial coccygeal cyst].
AB  - In acute inflammation of pilonidal sinus (PS), use of a laser scalpel permitted
      to reduce considerably the incidence of postoperative suppuration. Pain syndrome
      became less pronounced, or was absent, wound swelling disappeared at the early
      period. No differences in results of surgical treatment of uncomplicated PS at
      the stage of chronic inflammation in use of CO2-laser and conventional methods of
      treatment were noted. An original technique of operation for PS complicated by
      multiple fistulas, purulent leaks, pyodermia has been suggested. For plastic
      closure of a wound, the effect of laser photohydraulic preparation was used.
      Operated on was 31 patient, no disease recurrence was noted. Rough cicatricial
      deformity of the sacro-coccygeal region was absent.

PMID- 10912023
TI  - [The radical treatment of a suppurating epithelial coccygeal cyst and of a cyst
      of the sacrococcygeal area].
AB  - The results of treatment of 65 patients after radical excision of the suppurated
      pilonidal sinus and cyst of the sacro-coccygeal region with subsequent
      irradiation of the wound with scattered beam of the helium-neon laser are
      presented.

PMID- 10912024
TI  - [The programmed revision of the wound after the radical excision of an epithelial
      coccygeal cyst].
AB  - A method of programmed revision has been developed and used in 20 patients after
      excision of the pilonidal sinus.

PMID- 10912025
TI  - [The surgical treatment of diseases of the patent urachus].
AB  - In the clinic, 23 patients were operated on the weeping umbilicus. A patent
      urachus was revealed in 10 patients: its complete patency--in 3, a stone
      containing cyst--in 3, phlegmon of the abdominal wall--in 4. Total excision of
      the urinary duct was performed in all the patients.

PMID- 10912026
TI  - [The classification of the complications of sclerotherapy in esophageal varices].
AB  - A modified classification of complications of sclerotherapy of esophageal varices
      is presented.

PMID- 10912027
TI  - [Debatable questions in the surgical treatment of thoracic aortic aneurysms].
AB  - Some controversies in the surgical approach to thoracic aortic aneurysms are
      discussed. The author recommends: to perform echocardiography in patients with
      aortic aneurysms for detection of intracardiac pathology which may complicate the
      postoperative course; to combine thoracic aortography with selective coronary
      angiography in patients with thoracic aortic aneurysm for diagnosis of coronary
      artery disease; to operate asymptomatic fusiform aneurysm that measure twice or
      more the size of the normal aorta; to resect and replace dissections of the
      ascending aorta during cardio-pulmonary bypass; and to use active shunts during
      resection of the descending and thoraco-abdominal aneurysm.

PMID- 10912028
TI  - [The natural body resistance of patients operated on for differentiated thyroid
      cancer].
AB  - After operation for differentiated thyroid cancer, late assessment of the indices
      of cellular and humoral immunity was carried out in 37 patients ranging in age
      from 20 to 70 years. Control group included 38 healthy subjects of the similar
      age. In patients examined, increase in IgC content, absence of changes in IgA and
      IgM levels were noted. Relative content of B-lymphocytes was increased, total
      number of lymphocytes, T- and O-cells--significantly decreased.

PMID- 10912029
TI  - [The combined treatment of diabetic angiopathy of the lower extremities].
AB  - On the basis of treatment of 200 patients with diabetic angiopathy of the lower
      extremities, the authors have substantiated a differential approach to choice of
      a method for treatment depending on a stage of the disease. Use of quantum
      therapy, plasmapheresis, prolonged intraarterial infusion of the drugs together
      with conventional methods permitted to improve the functional results of
      treatment and avoid lethality during the recent five years.

PMID- 10912030
TI  - [The efficacy of the surgical hemostasis of a chest wall wound during operations
      on the "dry" heart under perfusion-free deep hypothermia].
AB  - The methods for reducing the blood loss by means of enhancing the effectiveness
      of the technique of surgical hemostasis of a thoracic wall wound--the main source
      of blood loss in operations on "dry" heart under conditions of perfusion-free
      hypothermia (27-26 degrees C) are considered. Minimal traumatization of the soft
      tissues of the thoracic wall and adhesions during thoracotomy performance and
      early wound closure with simultaneous warming of a patient contributes to 2-3
      fold reduction in blood loss and shortening of the time of operation by 40-60
      min.

PMID- 10912031
TI  - [The potentials of angiographic studies in the diagnosis of cardiovascular
      diseases].
AB  - Studies of the cardiovascular system in 1150 patients were performed by means of
      angiographic complex of the firm "Thompson" (USA) equipped with a computer "DG
      300" (USA). The morphofunctional characteristics of circulation--capacity of
      vascular bed, elasticity of a vessel, degree of its stenosis, time of circulation
      and perfusion were studied. Four (0.3%) patients developed complications: 2-
      bleeding from the femoral artery, 2--cardiac arrest during coronarography.

PMID- 10912032
TI  - [Pericholedochal lymphadenitis in complicated opisthorchiasis].
AB  - The data on frequency, location and pronouncement of pericholedochal
      lymphadenitis in complicated forms of chronic opisthorchiasis requiring surgical
      correction have been summarized. Pericholedochal lymphadenitis is caused by
      infection in the bile ducts which is the most frequently noted in cholestasis.
      The authors recommend to perform external drainage of the bile ducts with the aim
      of their sanation.

PMID- 10912033
TI  - [The validation of the use of iodine-containing suture thread in surgical
      practice].
AB  - Tissue response to the implanted iodine-containing thread and its antibacterial
      activity were studied in the experiment. When compared with the existing
      analogues, the thread studied, causes the lesser inflammatory response, has
      pronounced antimicrobial action and has no negative effect on the course of a
      wound process. Universality of antiseptic action of iodine creates wide
      possibilities for use of the threads in the surgical practice.

PMID- 10912034
TI  - [Ways to improve ambulatory surgery in the polyclinic of a medical health unit].

PMID- 10912035
TI  - [The prospects for the use of oculometric apparatus in the training of surgeons].

PMID- 10912036
TI  - [The problems of teaching surgery in a medical institute].

PMID- 10912038
TI  - [An instrument for applying the surgical suture].

PMID- 10912037
TI  - [The problem of endogenous intoxication].

PMID- 10912039
TI  - [The clinical characteristics of a postinjection suppurative-necrotic phlegmon].

PMID- 10912040
TI  - [Sepsis in patients with destructive mastitis].

PMID- 10912041
TI  - [Segmental resection of the breast in acute puerperal mastitis].

PMID- 10912043
TI  - [A foreign body of the abdominal cavity].

PMID- 10912042
TI  - [Acute anaerobic paraproctitis complicated by necrosis of the perineum and
      phlegmon of the left buttock, left thigh and leg].

PMID- 10912044
TI  - [The migration of a large foreign body of the soft tissues of the lower
      extremity].

PMID- 10912045
TI  - [Endometriosis of a postoperative scar].

PMID- 10912046
TI  - [An unusual complication of lymphatic paronychia].

PMID- 10912047
TI  - [Acute focal typhlitis].

PMID- 10912048
TI  - [Torsion of the fallopian tube with a cyst in a pregnant woman].

PMID- 10912049
TI  - [A rare complication of peptic pyloroduodenal stenosis].

PMID- 10912050
TI  - [The diagnosis and surgical treatment of a lateral cyst and fistula of the neck].
AB  - Surgical treatment was performed in 66 patients with lateral cyst and 23 with
      congenital single brachiogenic cervical fistula. In 14 patients, a cyst was
      complicated by a cervical phlegmon, 17 had a complete fistula, 6--incomplete one.
      In cyst diagnosis, the clinical signs and puncture of a cyst is of crucial
      importance, in fistula diagnosis--its connection with the pharynx--introduction
      of a dye. Removal of the uncomplicated cyst, spontaneously opened cyst-phlegmon
      (in 58 patients) and fistula (in 20) was performed with the use of the most
      cosmetic oblique-transverse incision. A lateral cyst often becomes infected and
      is subject to removal immediately alter establishment of the diagnosis. It is
      preferable to operate the patients with a lateral congenital cervical fistula non
      complicated by infection when they are under school age.

PMID- 10912052
TI  - [A method for the musculoaponeurotic plastic repair of complex abdominal
      hernias].
AB  - A method for plasty of the complex forms of postoperative and umbilical hernias
      is described. The muscular-aponeurotic edges of the hernial ring are sutured in
      such a way to make the peritoneal leaflet adjoin each other. Use of the method
      mentioned permits approximation of the similar tissues, reduction in their
      tension when suturing and maximum preservation of the volume of the abdominal
      cavity. Decrease in incidence of the disease recurrences from 40 to 16% was
      noted.

PMID- 10912051
TI  - [The prevention and treatment of suppurative-septic complications in patients
      with acute appendicitis].
AB  - In the experiment on mongrel dogs, the absorption of indigo carmine dye after its
      retroperitoneal administration with 10% dimexide solution into the lymphatic and
      venous systems was studied. More rapid delivery of a dye into the portal system,
      including the cases with portal hypertension, and into the lymphatic system was
      established. A method for retroperitoneal administration of antibiotics with 10%
      dimexide solution for prevention and treatment of purulent-septic complications
      in patients with acute appendicitis has been developed. The method was used in
      120 patients, the result of treatment is good.

PMID- 10912053
TI  - [The 3-wall plastic repair of the inguinal canal in the surgical treatment of
      inguinal hernia].
AB  - The method of plasty of the inguinal canal consisting in strengthening of its
      inferior wall achieved by means of placement of the sutures embracing the
      inguinal ligament permitting to prevent the development of its disfibration
      dissection and rupture of the fibers is suggested. One hundred and forty-one
      operation was performed. The long-term results were studied at the period of from
      2 to 10 years. Disease recurrence was noted in 1 (0.7%) patient.

PMID- 10912054
TI  - [The prevention of the occurrence of complications in patients with a
      postoperative abdominal hernia].
AB  - In 48 patients with postoperative abdominal hernia, oxygen therapy in the complex
      with therapeutic physical training was used 4 times a day for 15 min. The
      treatment resulted in elimination of hypoxemia, decrease in coagulative blood
      activity, normalization of the blood ABB, improvement of microcirculation. No
      postoperative complications were noted.

PMID- 10912055
TI  - [The clinico-diagnostic significance of the general antiprotease capacity of the
      blood in assessing endotoxicosis in suppurative-inflammatory diseases of the
      abdominal cavity organs].
AB  - The views upon the value of general antiprotease capacity of the blood in
      evaluation of endotoxicosis in purulent-inflammatory processes of the abdominal
      cavity are presented. One hundred and thirty one patient with diffuse
      peritonitis, acute pancreatitis and obstructive jaundice was examined. A role of
      bacterial proteases in exhaustion of the inhibitors at the example of Pseudomonas
      aeruginosa strain has been established. Use of protease inhibitors (contrykal
      etc.) only for strict indications is substantiated.

PMID- 10912056
TI  - [The diagnosis and treatment of patients with foreign bodies in the stomach and
      intestines].
AB  - The results of treatment of 39 patients with complications caused by presence of
      foreign bodies in the stomach and intestine are presented. Conservative treatment
      was performed in detection of a single foreign body with a length up to 10 cm.
      The foreign body staying at the same place for three days should serve an
      indication for operation. The emergency operation should be performed in presence
      of multiple foreign bodies in the stomach, when their length is more than 10 cm.
      and in development of complications--perforation of a hollow organ, development
      of hemorrhage, abscess, or infiltrate in the abdominal cavity.

PMID- 10912057
TI  - [The prevention of the entry of foreign bodies into the stomach and intestines].
AB  - On the basis of the results of treatment of 320 patients, the organization and
      sanitary-instructive measures aimed at prevention of getting, or development of
      the foreign bodies in the stomach and intestine are suggested. The primary
      prophylaxis (prevention of penetration of the substances which are alien to the
      organism into its cavities and tissues) and the secondary one (removal of the
      foreign bodies from the organism of a patient before their penetration into the
      intestine) are distinguished.

PMID- 10912058
TI  - [Combined surgical interventions on the organs of the abdominal cavity].
AB  - The results of treatment of 197 patients who underwent combined operations on the
      stomach, duodenum, small, large intestine and rectum, gallbladder and anterior
      abdominal wall are presented. The postoperative lethality was 1.6%. This didn't
      exceed its level in separate performance of the similar operations.

PMID- 10912059
TI  - [The surgical treatment of gastric and duodenal peptic ulcers in patients living
      in a radionuclide-contaminated area].
AB  - The state of cellular and humoral immunity in patients with gastric and duodenal
      ulcer disease residing at the territory contaminated with radionuclides (35
      patients) and at relatively clean (42) territory, as well as in 47 virtually
      healthy subjects was studied. It was established that in patients residing at
      contaminated territory, the ulcer diseases aggravated rapidly, the complications
      often occurred, and the immunologic indices didn't differ from those in patients
      residing at relatively clean territory.

PMID- 10912060
TI  - [A new method of cholecystectomy].
AB  - On the basis of the results of specially performed investigations on 47 complexes
      of the liver with extrahepatic bile ducts and gallbladder, a new method of
      cholecystectomy has been developed. In the clinic, 132 patients were operated on
      for cholelithiasis, acute and chronic cholecystitis. In performance of subserous
      cholecystectomy, a danger of injuring the vessels of the hepatoduodenal ligament
      is excluded, its adequate blood supply and that of hepatic parenchyma adjacent to
      the gallbladder is preserved.

PMID- 10912061
TI  - [Combined operations with resection of the colon for locally disseminated stomach
      cancer].
AB  - The 20-year experience with performance of combined interventions for locally
      spread gastric cancer is summarized. Resection of the stomach and colon was
      performed in 29 patients, gastrectomy with resection of the transverse colon--in
      28, gastrectomy with the variants of hemicolectomy--in 5. There were 19 radical
      operations, and 43 palliative ones. Gross invasion of gastric tumour into the
      colon was revealed in 36 patients. Of them in 19, it was histologically
      confirmed. The postoperative complications were noted in 19.3%, the postoperative
      lethality was 9.7%.

PMID- 10912062
TI  - [Treatment methods for primary cancer of the lower lip].
AB  - The long-term results of treatment of primary cancer of a lower lip were studied
      in 954 patients. It was established that cryodestruction was the most effective
      method for treatment of I and IIA stage squamous cell keratinizing type cancer of
      a lower lip irrespective of its clinical form. In tumour spreading to the corner
      of a mouth, and in IIIA stage tumour, use of radiation methods of treatment as
      the independent ones (close-focus roentgenotherapy and long-focus gamma-therapy)
      has proved to be of low effectiveness.

PMID- 10912063
TI  - [The late results of surgical intervention in radically inoperable stomach
      cancer].
AB  - A long-term result of palliative operations, as well as that of exploratory
      laparotomy in 74 patients with gastric cancer was studied. In patients with
      suspected radically inoperable form of gastric cancer, the efforts should be made
      to remove a neoplasm, i.e. gastric resection to be performed.

PMID- 10912064
TI  - [The surgical treatment of patients with colonic cancer complicated by perifocal
      inflammation of the tissues].
AB  - In the clinic, at preoperative preparation of the patients with cancer of the
      colon complicated by perifocal inflammation, the irrigation of a tumour area,
      using antibacterial preparations, is employed. After laparoscopy, a drainage tube
      with microirrigator for perfusion of the antibacterial solution is introduced to
      the region of tumour location. Using the method described, 25 patients were
      prepared for the operation. Their state improved after 7-8 days. One-stage
      radical operation was performed in 20 patients. Of them in 17, primary intestinal
      anastomosis was created.

PMID- 10912065
TI  - [The diagnostic value of determining the level of the carbohydrate antigen 19-9
      in pancreatic cancer].
AB  - By means of a radioimmunologic method, the serum level of carbohydrate antigen
      (CA) 19-9 was measured in 96 patients, including 17 with pancreatic cancer, 35-
      with inflammatory diseases of the pancreas, 44--with cancer of another location.
      CA 19-9 level in patients with pancreatic cancer was considerably higher than in
      patients with other diseases and controls.

PMID- 10912066
TI  - [The prevention and treatment of cicatricial esophageal stenosis after the
      correction of atresia].
AB  - On the basis of the experience with treatment of esophageal atresia in 86
      patients, it was established that cicatricial stenosis of the esophagus after
      radical correction of a defect occurs as a consequence of anastomotic suture
      failure, violation of the technique of placing an anastomosis, gastro-esophageal
      reflux. The recommendations on prevention and treatment of cicatricial esophageal
      stenosis are given.

PMID- 10912067
TI  - [Intrapleural sorption detoxication in the combined treatment of acute
      destructive pneumonia in children].
AB  - The pathogenetic substantiation and technique of intrapleural sorption
      detoxication (IPSD) based on the use of high-dispersed silicone dioxide (trade
      mark "AEROSIL") are presented. Use of IPSD in the complex of treatment of 25
      children with complicated forms of acute destructive pneumonia permitted to
      shorten the duration of intoxication syndrome, sanation of suppurative foci, stay
      of the patients at a hospital.

PMID- 10912069
TI  - [The diagnosis and treatment of benign lymphoreticulosis in children].
AB  - The experience with diagnosis and treatment of benign lymphoreticulosis in 26
      children at the age of from 1 year and 9 mos to 14 years has been summarized. The
      involvement of the axillary and ulnar lymph nodes was the most frequent.
      Diagnosis was established on the basis of data of history, typical clinical signs
      of the disease, results of histologic study and serologic reactions. Maximum
      possible removal of the lymph nodes involved, antibacterial, desensibilizing and
      anti-inflammatory therapy were performed. All the patients recovered.

PMID- 10912068
TI  - [Rare forms of partial gigantism due to vascular hypoplasia].
AB  - On the basis of findings of angiographic studies performed in 35 patients with
      partial gigantism of the upper and lower extremities, the two types of
      developmental anomaly of the vessels have been distinguished.

PMID- 10912070
TI  - [The use of the CO2 laser in the combined treatment of chronic osteomyelitis in
      children].
AB  - The results of performance of sanation according to the conventional technique
      and with the use of CO2-laser in chronic osteomyelitis in 73 children have been
      analysed. Use of the CO2-laser contributed to improvement of quality of sanation,
      increase in incidence of an operative wound healing by first intention, reduction
      in duration of hospital treatment of a patient, improvement of the long-term
      results.

PMID- 10912071
TI  - [The surgical procedure in testicular torsion in children].
AB  - The results of treatment of 37 children with torsion of a testicle, including 18
      (48.6%) under 2 years of age, are presented. In doubtful viability, a testicle
      after untwisting was placed into its bed and observed for 12-24 h. Orchiectomy
      was performed only in total lack of viability. A testicle was preserved in
      24(64.8%) of the 33 patients. Two to five years after the operation, a good
      result was noted in 11, a satisfactory one--in 8, and unsatisfactory one--in 5
      patients.

PMID- 10912072
TI  - [The organization of the work of a department of surgical infection and
      proctology in a provincial hospital].

PMID- 10912073
TI  - [Methods for the cryosurgical treatment of hemorrhoids].

PMID- 10912074
TI  - [Current problems in the treatment of acute appendicitis].

PMID- 10912075
TI  - [Acute phlegmonous appendicitis simulating right-sided paranephritis].

PMID- 10912076
TI  - [A case of the complex diagnosis of acute appendicitis].

PMID- 10912077
TI  - [A rare case of obstruction of the large intestine].

PMID- 10912078
TI  - [A method for appendectomy].

PMID- 10912079
TI  - [A device for the local treatment of diseases of the distal large intestine].

PMID- 10912080
TI  - [Posttraumatic cicatricial stenosis of the upper and middle third of the left
      half of the colon].

PMID- 10912081
TI  - [A lipoma of the small intestine as the rare cause of the occurrence of
      intestinal hemorrhage].

PMID- 10912082
TI  - [A case of iatrogenic early postoperative adhesive intestinal obstruction after
      its extensive resection].

PMID- 10912083
TI  - [A case of combined inguinal hernia in a patient with rheumatoid polyarthritis].

PMID- 10912084
TI  - [A combined inguinal hernia].

PMID- 10912086
TI  - [Wound suppuration following herniotomy].

PMID- 10912085
TI  - [A pseudostrangulated hernia].

PMID- 10912087
TI  - [Torsion of the epiploic process of the large intestine in combination with acute
      appendicitis].

PMID- 10912088
TI  - [A ligature fistula of the stump of the meso-appendix].

PMID- 10912089
TI  - [A combination of acute phlegmonous appendicitis and an echinococcal cyst of the
      appendix].

PMID- 10912090
TI  - [The finding of the appendix in a hernial sac].

PMID- 10912091
TI  - [A combination of destructive forms of acute appendicitis and diverticulitis].

PMID- 10912092
TI  - [The diagnosis of closed injuries to the Achilles tendon].

PMID- 10912093
TI  - [How Germany manages it's diabetic patients].

PMID- 10912094
TI  - [New insulin sensitizers].

PMID- 10912095
TI  - [Obese type 2 diabetic patients. Faulty nutrition?].

PMID- 10912097
TI  - [In AT-III deficiency: heparin or hirudin?].

PMID- 10912096
TI  - [New European guidelines for type 2 diabetic patients. Vascular protection
      instead of blood glucose cosmetic management].

PMID- 10912098
TI  - [Nerve gas for facial creases?. Interview by Dr. Beate Schumacher].

PMID- 10912099
TI  - [A new method of coronary angiography. Imaging without intervention].

PMID- 10912100
TI  - [Drug therapy of chronic pain. A practical approach].
AB  - The management of chronic pain has been distinctly facilitated by the
      introduction of slow-release forms of various types of analgesics. The WHO ladder
      continues to represent a useful guide for the management of the patient with
      chronic pain, but should neither be binding on the physician nor restrict his
      options. In principle, it makes good sense to gain experience with a small number
      of analgesics. For combatting severe pain, morphine is the most reliable weapon.
      For all medications, the principle applies that they should be used on a regular
      and purposeful basis. The next dose should be taken before the pain reappears. In
      the case of anxiety, depression or nausea, additional medications may often be
      indicated. In some patients, in particular those with neuropathic pain, pumps for
      long-term application, or invasive techniques may be needed. These patients could
      benefit considerably from the care provided by pain specialists or
      interdisciplinary pain clinics.

PMID- 10912101
TI  - [Radiotherapy for tumor pain. Long-term freedom from pain with minimal side
      effects].
AB  - Radiotherapy may be the treatment of choice in patients suffering pain from early
      stage cancer and is used in curative intent. In addition, it is often used for
      palliative treatment in advanced tumor disease, when, thanks to local regression
      of the tumor, pain relief may be long-term and achieved with only mild or
      moderate side effects.

PMID- 10912102
TI  - [Oncologic pain therapy. Are there alternatives to pills and high-tech?].
AB  - State of the art pain management has to recognize physiologic, sensory,
      affective, cognitive, behavioural and sociocultural dimensions of the experience
      of cancer pain. This means that non-pharmacologic measures with effects on the
      subjective and affective situation of the patient may also be of benefit in pain
      management. However, restraint must be exercised in translating the positive
      results achieved with certain such measures in the treatment of benign pain to
      patients with cancer. Physiotherapy, psychology and psychotherapy should be used
      to expand pharmacologic and radiotherapeutic measures, but should not delay or
      replace them.

PMID- 10912103
TI  - [Internet addresses on the main topic. Pain therapy in oncology].

PMID- 10912104
TI  - [Conscientious evaluation of measuring accuracy. Hypertension League provides
      approval seals for automatic blood pressure units].

PMID- 10912105
TI  - [Treatment of hypertension. Between progress and cost control].

PMID- 10912106
TI  - [Diagnosis of polygenic diseases. Predictive gene tests--do they help the
      patient?].

PMID- 10912107
TI  - [Rubella in pregnancy and childhood. Diagnosis, prevention and therapy].

PMID- 10912108
TI  - [Fulminant lung embolism in heparin treatment. Heparin-induced thrombocytopenia
      type II].

PMID- 10912109
TI  - [A family physician on the National Health Insurance Action Program. This is how
      I deal with it].

PMID- 10912110
TI  - [Dr. Frank Ulrich Montgomery sounds the alarm. Young physicians are massively
      overloaded. Interview by Werner Loosen].

PMID- 10912111
TI  - [Family physician Dr. Friedrich Hach. Hospitals save--we pay the difference.
      Interview by Werner Loosen].

PMID- 10912112
TI  - [New breakthrough for ACE inhibitors. HOPE Study: hope for all vascular
      patients?].

PMID- 10912113
TI  - ["The minor difference" in coronary heart disease. When the heart of a woman
      breaks].

PMID- 10912114
TI  - [Is placebo a kind of mental healing?].

PMID- 10912115
TI  - [Exciting pictures from the internet. Embryo development per mouse click].

PMID- 10912116
TI  - [For 1,200 Marks per month 24-hour availability every day. How do physicians
      without boundaries live?. Interview by Dr. Beate Schumacher].

PMID- 10912117
TI  - [Primary coronary heart disease prevention in general practice. How does one
      recognize and define a risk patient?].
AB  - The major factors for atherosclerosis and atherosclerotic disease, such as
      coronary heart disease and cerebral or peripheral vascular disease are well
      known. An individual risk profile can be identified by careful history-taking
      supplemented by the measurement of a few objective parameters. This individual
      risk profile should be established as early as possible, and appropriate
      treatment instituted, since it has been shown that overall mortality as well as
      the morbidity and mortality associated with coronary artery disease can be
      decreased by more than 25% by such an approach.

PMID- 10912119
TI  - [New kidney, but a sick heart. Why many patients with renal failure and kidney
      transplant patients die of cardiovascular disease].
AB  - Renal insufficiency and dialysis is associated with hypertriglyceridemia caused
      by a decreased activity of the enzyme lipoprotein lipase. Peritoneal dialysis is
      further complicated by hypercholesterolemia due to an increase in the synthesis
      of VLDL by the liver, stimulated by a rise in glucose absorption from the
      peritoneal dialysate. The treatment of choice is a lipid lowering diet. If
      necessary, fibrates should be given in a dose adjusted to the renal failure.
      Hypercholesterolemia should be treated with HMG-CoA reductase inhibitors. Serum
      cholesterol is elevated in more than one-half of the patients with glomerular
      disease and protein-urea. The consequences are high rate of cardiovascular
      disease and accelerated progression of the glomerular disease, which can also be
      slowed by HMG-CoA reductase inhibitors. In 60 to 80% of the patients undergoing
      kidney transplantation, a cholesterol level of more than 250 mg/dl induced by
      corticosteroids and immunosuppressants is observed. Cardiovascular mortality is
      high (> 50%), with hypercholesterolemia being a major risk factor. There is
      evidence to show that increased cholesterol levels can shorten the survival time
      of transplanted kidneys. The treatment of choice is HMG-CoA reductase inhibitors
      which, to avoid the development of rhabdomyolysis should be used at a reduced
      dose when given together with cyclosporine or tacrolimus.

PMID- 10912118
TI  - [When lipids increase in dialysis: the role of heparin! Standard heparin
      increases, low-molecular-weight heparin lowers triglycerides].
AB  - Dyslipoproteinemia in patients on hemodialysis is characterized by a decrease in
      high density lipoprotein (HDL), cholesterol, hypertriglyceridemia, increased
      triglyceride-rich lipoproteins, such as very low density lipoprotein (VLDL) and
      intermediate density lipoprotein (IDL), a higher proportion of the small dense
      low density lipoprotein (small dense LDL) subfraction, and higher lipoprotein(a)
      concentration. The reason for the changes in triglyceride metabolism is an
      increase in the production of apolipoprotein B, and a decrease in the metabolism
      of VLDL as a consequence of decreased endothelial cell delipidation. The
      endothelial lipoprotein lipase, which plays a major role in this process, is
      released by heparin, which is essential for the function of the enzyme. Repeated
      administration of heparin for anticoagulation during hemodialysis apparently
      leads to an LPL depletion in the endothelium. This results in further exhaustion
      of lipolysis. Clinical studies in hemodialysis patients with high triglyceride
      and cholesterol levels indicate that a change from standard heparin to low
      molecular-weight heparin improves the lipid profile by lowering triglycerides and
      cholesterol.

PMID- 10912120
TI  - [Irritable bowel syndrome. Not to be examined too frequently!].

PMID- 10912121
TI  - [Thrombosis ABC, 5: No prophylaxis without bleeding risk. Safe navigation between
      Scylla and Charybdis].

PMID- 10912122
TI  - [Counseling before and during pregnancy. 1: Genetic counseling, risk of maternal
      age].

PMID- 10912123
TI  - [Young man with abdominal pain. Obstruction of the small intestine].

PMID- 10912124
TI  - [A regression wave rolls toward us. How to defend yourself].

PMID- 10912125
TI  - [Helicobacter test threatened by regression. Cost saving not allowed!].

PMID- 10912126
TI  - [Successful desensitization. Then the quality of life also improves].

PMID- 10912127
TI  - [Antibiotic therapy. Strong bacteriocidal effect prevents development of
      resistant pathogens].

PMID- 10912128
TI  - [Generalized social anxiety disorders: recognized too rarely].

PMID- 10912129
TI  - [Ceramide-containing cream. Skin barrier is repaired].

PMID- 10912130
TI  - [Prevention of ischemic complications. ACE inhibitor helps in endothelial
      crisis].

PMID- 10912131
TI  - [1. Diabetes mellitus: discrepancy between claims and reality].

PMID- 10912132
TI  - [In backache rapid minimal diagnosis is enough].

PMID- 10912133
TI  - [Liposuction, yes--but not for overweight patients].

PMID- 10912134
TI  - [Many ways lead to the same goal].

PMID- 10912135
TI  - [A drink for fat cells].

PMID- 10912136
TI  - [Dioxin poisoning: fasting is risky].

PMID- 10912137
TI  - [New hope in dystonia, tremor and Parkinson disease? A pacemaker for the brain.
      Interview by Dr. Christina Berndt].

PMID- 10912138
TI  - [Infants with screaming attacks. Staying cool and determining the etiology].

PMID- 10912139
TI  - [Promoting self examination! Testicular carcinoma: 200 fatalities too many].

PMID- 10912140
TI  - [Sore throat in general practice. Minimizing diagnosis--preventing superfluous
      use of antibiotics].
AB  - Sore throat usually is caused by viral pharyngitis, in about 15 to 30% by group A
      beta-haemolytic streptococci. Based on current concepts a guideline for the
      management in general practice is developed. If the typical symptoms of
      streptococcal pharyngo-tonsillitis are present--serious sore throat, fever more
      than 38.5 degrees C, purulent tonsillar exsudate, painful cervical
      lymphadenopathy, lack of cough or rhinorrhea--without any other diagnostic
      procedure penicillin is given for ten days. Only in cases of doubt throat swabs
      are taken for rapid diagnostic test and culture. The implementation of the
      guideline permits differentiation between viral pharyngitis and streptococcal
      tonsillitis by simple questions and physical examination and prevention of
      unnecessary diagnostics and antibiotic overuse.

PMID- 10912141
TI  - [Sore throat consultation--what is the value of a treatment guideline?].
AB  - OBJECTIVE: To investigate the possibility of rationalizing the management of sore
      throat in the doctor's office with the aid of appropriate guidelines. PATIENTS
      AND METHODS: Part 1 was designed as a retrospective study involving two
      comparative groups: A1 under the care of general practitioner (GP) A, and B1
      under the care of GP B. Part 2 was designed as a randomized prospective study
      involving two comparative groups and intervention: A2 under the care of GP A with
      no intervention, and B2 treated by GP B with intervention. The study was
      conducted in the group practice of the two GPs, located in a middle-sized town.
      Guidelines for the differential management of sore throat was developed. An
      overall total of 1010 patients with sore throat were divided into 4 groups, and
      their epidemiological data, care criteria (throat swabs, antibiotics) and
      effectiveness criteria (success rate, relapses) evaluated statistically using the
      Instat Guide program to identify guideline-influenced effects. RESULTS: No
      significant differences were to be seen between the three groups receiving
      routine care. In the guideline-oriented group, however, significant changes were
      observed (P < 0.01): more frequent identification of viral pharyngitis in
      comparison with other underlying clinical causes, a decrease in the frequency of
      throat swabs from 32% to 7%, and a decrease in the use of antibiotics from 51% to
      31%, with the success and relapse rates remaining virtually unchanged.
      CONCLUSION: The implementation of the guidelines results in the avoidance of
      unnecessary diagnostic measures and the overuse of antibiotics, while ensuring
      high-quality care and a high level of feasibility in the day-to-day work of the
      doctor's office.

PMID- 10912142
TI  - [Palliation of bone pain in metastatic prostate carcinoma. Value of radionuclide
      therapy with rhenium 186 HEDP].
AB  - Pain caused by bone metastases from carcinoma of the prostate are treated in
      particular by non-steroidal anti-inflammatory drugs and opioid-containing
      analgesics. In case of painful multilocular metastases, the use of osteotropic
      radionuclides which selectively irradiate the bone metastases while sparing
      healthy surrounding tissue offers an alternative. Owing to their favorable
      physical properties, rhenium-186 and samarium-153 are preferentially used. The
      rate of side effects--for the most part transient thrombocytopenia--is low, and
      the response rate is roughly 70 to 80% of the patients treated. Pain relief may
      last for between 1 and 6 months, with the option of multiple treatments. The
      prognosis of the disease is, however, not affected.

PMID- 10912143
TI  - [After myocardial infarct fit again for career].

PMID- 10912144
TI  - [Psoriasis symptoms improved by tonsillectomy].

PMID- 10912145
TI  - [How many cases of rhinitis are allergically-induced? Cave: Increase in
      sensitization].

PMID- 10912146
TI  - [Therapy of allergic rhinitis: recommendations of US-American experts. Critical
      evaluation of 1st generation antihistaminics].

PMID- 10912147
TI  - [Odor test: spray dose instead of inhalation bottle. Orienting smell evaluation
      simplified].

PMID- 10912148
TI  - [Counseling before and during pregnancy. 2: In vitro fertilization, status after
      miscarriage, gynecologic diseases, drugs].

PMID- 10912149
TI  - [Tachycardia and abdominal pain. Embolism-induced mesenterial infarct in atrial
      fibrillation].

PMID- 10912150
TI  - [Barmer model trial of phyto-pharmaceuticals. Alternative methods are under
      scrutiny. Interview by Dr. T. U. Keil].

PMID- 10912151
TI  - [Dementia or depressive pseudodementia? Rapid test for general practice].

PMID- 10912152
TI  - [Antihistaminics for urticaria. Scratching or yawning--alternatives of the past].

PMID- 10912153
TI  - [After removal of a malignant melanoma. Enhancing the immune system!].

PMID- 10912154
TI  - [Asthma therapy: exercise training improves everyday competence of the patient].

PMID- 10912155
TI  - [A-II blocker or ACE inhibitor in heart failure? Captopril can't be beat].

PMID- 10912156
TI  - [Interview with the author of ELITE II. Cave: small studies of fatal illnesses].

PMID- 10912158
TI  - [Laser beams into the middle of the heart. First angina at rest, then without
      symptoms].

PMID- 10912157
TI  - [A new class of potent antihypertensive agents. Especially systolic pressure is
      significantly reduced].

PMID- 10912160
TI  - [Aseptic femur head necrosis. Does shockwave therapy make an operation
      superfluous?. Interview by Bodo Dorra].

PMID- 10912159
TI  - [Certified continuing education online. Continuing education at home!].

PMID- 10912161
TI  - [Increased incidence of bronchial carcinomas. What is new in therapy and
      diagnosis?].
AB  - The increasing incidence and continuing poor prognosis of lung cancer make new
      therapeutic concepts necessary. For stage I and stage II disease, surgery remains
      the treatment of choice. In the case of inoperable patients, radiotherapy, used
      alone, may be a curative alternative. To improve the prognosis of stages II and
      III of non-small-cell lung cancer, multi-modal treatments such as neoadjuvant
      chemotherapy, combined chemo-/radiotherapy and post-operative irradiation are
      still being researched. Although present results indicate higher survival rates,
      these approaches have not yet become standard. The palliative options for stages
      III and IV have also clearly been expanded in recent years, so that late-stage
      lung cancer may yet respond to treatment. Such options are, in particular,
      invasive bronchoscopic procedures, such as treatment with the Nd-YAG laser,
      cryotherapy, dilatation and the implantation of stents, or intraluminal
      irradiation. The major and decisive measure, however, is still prevention which,
      for 85% of all lung cancer consists in the rejection of nicotine abuse. In the
      meantime, sensitive methods of early diagnosis have also become available.
      However, they are invasive and thus not suitable for large-scale screening, but
      are reserved for high-risk patients. Non-invasive methods are currently under
      development.

PMID- 10912162
TI  - [Internet addresses on the main topic. Bronchial carcinoma].

PMID- 10912163
TI  - [Information the family physician gives his patients to take home. Utilization,
      contents and origin of printed information].
AB  - Providing the patient with information is one of the most important tasks of the
      family doctor, both for legal and medical reasons. Apart from verbal information,
      a wealth of printed material is also available. In a survey of 62 randomly
      selected general practices, the volume and nature of such information material
      was investigated, and its importance in practice established by means of an
      interview. 88.7% of the doctors interviewed stated that they handed out printed
      matter every day, and 96.8% considered the availability of such information to be
      an important aid in their daily work. Most of the printed information dealt with
      metabolic and cardiovascular disorders, and 93.5% of the material was supplied by
      the pharmaceutical industry. This means that other institutions which have a task
      to inform patients are virtually not represented in the doctor's office. Printed
      material providing health-promoting information, for example, on such topics as
      smoking, AIDS, exercise, healthy eating and suchlike, were lacking. The data
      point to an urgent need for additional information material in the doctor's
      office.

PMID- 10912164
TI  - [When leg tissue slowly becomes edematous... Thrombosis ABC, 7: Chronic venous
      insufficiency].

PMID- 10912165
TI  - [Recent fluoroquinolones. Highly effective weapons for ambulatory therapy].

PMID- 10912166
TI  - [From atopic eczema to T-cell lymphoma. Morphologically and descriptively
      oriented dermatologic diagnosis (7)].

PMID- 10912167
TI  - [After baptism a red cross appeared on the forehead. Not a miracle--only a
      phototoxic reaction to perfume essence].

PMID- 10912168
TI  - [Dog and cat as source of infection. Highly contagious fungi are transmitted].

PMID- 10912169
TI  - [Counseling before and during pregnancy. 5: Stress on the cardiovascular system].

PMID- 10912170
TI  - [Diagnostic quiz. Pericardial tamponade in a 65-year-old woman. Hypothyroidism].

PMID- 10912171
TI  - [C. Kroegel on "Asthma therapy in a double-pack". Compliance next to the
      toothbrush. Interview by Dr. med. Julia Rautenstrauch].

PMID- 10912172
TI  - [Bacterial superinfection in bronchitis. Chief pathogens under scrutiny].

PMID- 10912173
TI  - [2. ECG quiz: Cases as they appear in your practice].

PMID- 10912174
TI  - Influence of mechanical forces on cells and tissues.

PMID- 10912175
TI  - Cell mechanotransduction and interactions with biological tissues.
AB  - The biomechanical mechanisms involved in the processes of tissue remodeling and
      adaptation are reviewed with emphasis on mechanotransduction at the cellular
      level. New theoretical models associated with experimental rheological techniques
      are briefly commented.

PMID- 10912176
TI  - The deformation behavior and viscoelastic properties of chondrocytes in articular
      cartilage.
AB  - Chondrocytes in articular cartilage utilize mechanical signals in conjunction
      with other environmental factors to regulate their metabolic activity. However,
      the sequence of biomechanical and biochemical events involved in the process of
      mechanical signal transduction has not been fully deciphered. A fundamental step
      in determining the role of various factors in regulating chondrocyte activity is
      to characterize accurately the biophysical environment within the tissue under
      physiological conditions of mechanical loading. Microscopic imaging studies have
      revealed that chondrocytes as well as their nuclei undergo shape and volume
      changes in a coordinated manner with deformation of the tissue matrix. Through
      micromechanical experiments, it has been shown that the chondrocyte behaves as a
      viscoelastic solid material with a mechanical stiffness that is several orders of
      magnitude lower than that of the cartilage extracellular matrix. These properties
      seem to be due to the structure of the chondrocyte cytoskeleton, and in part, the
      viscoelastic properties of the cell nucleus. The mechanical properties of the
      pericellular matrix that immediately surrounds the chondrocyte significantly
      differ from those of the chondrocyte and the extracellular matrix, suggesting
      that the pericellular matrix plays an important role in defining the mechanical
      environment of the chondrocyte. These experimentally measured values for
      chondrocyte and cartilage mechanical properties have been used in combination
      with theoretical constitutive modeling of the chondrocyte within articular
      cartilage to predict the non-uniform and time-varying stress-strain and fluid
      flow environment of the cell. The ultimate goal of these studies has been to
      elucidate the sequence of biomechanical and biochemical events through which
      mechanical stress influences chondrocyte activity in both health and in disease.

PMID- 10912177
TI  - Loading-induced changes in synovial fluid affect cartilage metabolism.
AB  - The object of this study was to determine whether changes in the synovial fluid
      (SF) induced by in vivo loading can alter the metabolic activity of chondrocytes
      in vitro, and, if so, whether insulin-like growth factor-I (IGF-I) is responsible
      for this effect. Therefore, SF was collected from ponies after a period of box
      rest and after they had been exercised for a week. Normal, unloaded articular
      cartilage explants were cultured in 20% solutions of these SFs for 4 days and
      chondrocyte bioactivity was determined by glycosaminoglycan (GAG) turnover (i.e.,
      the incorporation of 35SO4 into GAG and the release of GAG into the medium).
      Furthermore, the extent to which the bioactivity is IGF-I-dependent was
      determined in a cartilage explant culture in 20% SF, in the presence and absence
      of anti-IGF-I antibodies. In explants cultured in post-exercise SF, GAG synthesis
      was enhanced and GAG release was diminished when compared to cultures in pre
      exercise SF. SF analysis showed that IGF-I and IGFBP-3 levels were increased in
      post-exercise SF. There was a positive correlation between IGF-I levels and
      proteoglycan synthesis, but no correlation between IGF-I levels and proteoglycan
      release. Addition of anti-IGF-I antibodies significantly inhibited stimulation of
      proteoglycan synthesis in explants cultured in SF with 40%. However, there was no
      difference in inhibition of proteoglycan synthesis between pre- and post-exercise
      SF which indicated that the relative contribution of IGF-I in the stimulating
      effect of SF did not change. Proteoglycan release was not influenced by the
      presence of anti-IGF-I antibodies. It is concluded that chondrocyte metabolic
      activity is at least partially regulated by changes in the SF induced by in vivo
      loading. Exercise altered the SF in a way that it had a favourable effect on
      cartilage PG content by enhancing the PG synthesis and reducing the PG breakdown.
      IGF-I is an important contributor to the overall stimulating effect of SF on
      cartilage metabolism. It is, however, unlikely that IGF-I is the only mediator in
      the exercise-induced increase in this stimulating effect.

PMID- 10912178
TI  - Frictional behaviour of bovine articular cartilage.
AB  - The experimentally measured indentation displacement and friction of normal and
      degraded (treated with chondroitinase AC) bovine articular cartilage plugs
      against a smooth steel plate were compared with the predictions based on the
      biphasic theory using the finite element method. It was found that the measured
      indentation displacement of both cartilage specimens could be predicted from the
      biphasic theory and the permeability for the degraded cartilage specimen was
      increased approximately three times. However, the measured friction coefficient
      was much lower for short period of loading, and the difference in the finite
      element prediction of friction coefficient between the normal and degraded
      cartilage specimens was not observed in the experiment. Therefore, it was
      concluded that both biphasic and other mechanisms were important in controlling
      the frictional and lubricating characteristics of articular cartilage in mixed
      and boundary lubrication regimes.

PMID- 10912179
TI  - Chondrocyte regulation by mechanical load.
AB  - The effects of load on articular cartilage are complex. Dynamic loading of
      cartilage is associated with slight cell and tissue deformation as well as
      cyclical fluctuations in the hydrostatic pressure of cartilage and in fluid
      movement. Static loading results in expression of fluid from the tissue,
      concentrating extracellular matrix macromolecules and consequently increasing the
      concentrations of cations, reducing extracellular pH and increasing extracellular
      osmolarity. Each of these alterations is implicated in regulating the synthetic
      response of chondrocytes to load. However, the mechanisms by which these changes
      affect matrix turnover are poorly understood. In this review we consider how load
      may affect chondrocyte behaviour through its influence on membrane transport
      processes and thus on the intracellular environment.

PMID- 10912180
TI  - Intercellular Ca2+ waves in mechanically stimulated articular chondrocytes.
AB  - Articular cartilage is a tissue designed to withstand compression during joint
      movement and, in vivo, is subjected to a wide range of mechanical loading forces.
      Mechanosensitivity has been demonstrated to influence chondrocyte metabolism and
      cartilage homeostasis, but the mechanisms underlying mechanotransduction in these
      cells are poorly understood. In many cell types mechanical stimulation induces
      increases of the cytosolic Ca2+ concentration that propagates from cell to cell
      as an intercellular Ca2+ wave. Cell-to-cell communication through gap junctions
      underlies tissue co-ordination of metabolism and sensitivity to extracellular
      stimuli: gap junctional permeability to intracellular second messengers allows
      signal transduction pathways to be shared among several cells, ultimately
      resulting in co-ordinated tissue responses. Mechanically-induced Ca2+ signalling
      was investigated with digital fluorescence video imaging in primary cultures of
      rabbit articular chondrocytes. Mechanical stimulation of a single cell, obtained
      by briefly distorting the plasmamembrane with a micropipette, induced a wave of
      increased Ca2+ that was communicated to surrounding cells. Intercellular Ca2+
      spreading was inhibited by 18 alpha-glycyrrhetinic acid, suggesting the
      involvement of gap junctions in signal propagation. The functional expression of
      gap junctions was assessed, in confluent chondrocyte cultures, by the
      intercellular transfer of Lucifer yellow dye in microinjection experiments while
      the expression of connexin 43 could be detected in Western blots. A series of
      pharmacological tools known to interfere with the cell calcium handling capacity
      were employed to investigate the mechanism of mechanically-induced Ca2+
      signalling. In the absence of extracellular Ca2+ mechanical stimulation induced
      communicated Ca2+ waves similar to controls. Mechanical stress induced Ca2+
      influx both in the stimulated chondrocyte but not in the adjacent cells, as
      assessed by the Mn2+ quenching technique. Cells treatment with thapsigargin and
      with the phospholipase C inhibitor U73122 blocked mechanically-induced signal
      propagation. These results provide evidence that in chondrocytes mechanical
      stimulation activates phospholipase C, thus leading to an increase of
      intracellular inositol 1,4,5-trisphosphate. The second messenger, by permeating
      gap junctions, stimulates intracellular Ca2+ release in neighbouring cells.
      Intercellular Ca2+ waves may provide a mechanism to co-ordinate tissue responses
      in cartilage physiology.

PMID- 10912181
TI  - Transcriptional activation in chondrocytes submitted to hydrostatic pressure.
AB  - At present, only a little is known about the transcriptional regulation in
      chondrocytes submitted to various physicomechanical factors known to exist in
      articular cartilage. Recently, we have investigated the effects of hydrostatic
      pressure on transcriptional control in chondrocytes using human chondrosarcoma
      and immortalized chondrocyte cell lines for the experiments. Hydrostatic pressure
      was applied on the cells in a special computer-controlled, water-filled pressure
      chamber, where cyclic and static pressures up to 32 MPa can be created.
      Differential display RT-PCR and probing of cDNA arrays are the methods we have
      used to study differential gene expression due to hydrostatic pressure. By
      differential display RT-PCR experiments, we have observed several differentially
      expressed cDNA bands under continuous 30 MPa hydrostatic pressure, while 30 MPa
      cyclic pressure at 1 Hz produced much fewer changes. In the first phase of our
      studies, we have focused on the effects of 30 MPa hydrostatic pressure because it
      causes a unique hsp70-mediated stress response in immortalized chondrocytes.
      Differential display RT-PCR screening provided us with several clones that derive
      from low-abundance mRNAs, such as death-associated protein 3 (DAP3), a nucleotide
      binding protein which increases due to interferon-gamma induced cell death; PTZ
      17 (or p311), a seizure-related protein; H-NUC, a nuclear DNA binding protein;
      and one new gene of unknown function. In Northern blots, an induction was
      confirmed for the new gene, DAP3 and PTZ-17 were down-regulated in some but not
      in all parallel experiments; however, basal level of H-NUC mRNA was too low to be
      detected in Northern blots. We then chose to widen our screening to a number of
      known genes arrayed as cDNA blots. Under 30 MPa continuous hydrostatic pressure,
      four different time points were chosen (0, 3, 6 and 24 h) for the experiments.
      The screening of 588 cDNAs showed 15 up-regulated and 6 down-regulated genes.
      Consistently with our previous results hsp70 was highly induced, as well as
      hsp40, a chaperone protein functioning together with hsp70. Gadd45 and to a
      lesser extent Gadd153 (stress genes induced by, e.g., ionizing radiation and
      ischaemia) were up-regulated, as well as p21waf1,cip1, a protein participating in
      cell cycle regulation that can interact with Gadd45. Northern blots confirmed
      Gadd45 induction. Down-regulated transcripts included, e.g., DAD-1, glutathione S
      transferase pI, DNA-binding inhibitor ID-1H, and cytoplasmic dynein light chain.

PMID- 10912182
TI  - Effects of shear stress on articular chondrocyte metabolism.
AB  - The articular cartilage of diarthrodial joints experiences a variety of stresses,
      strains and pressures that result from normal activities of daily living. In
      normal cartilage, the extracellular matrix exists as a highly organized composite
      of specialized macromolecules that distributes loads at the bony ends. The
      chondrocyte response to mechanical loading is recognized as an integral component
      in the maintenance of articular cartilage matrix homeostasis. With inappropriate
      mechanical loading of the joint, as occurs with traumatic injury, ligament
      instability, bony malalignment or excessive weight bearing, the cartilage
      exhibits manifestations characteristic of osteoarthritis. Breakdown of cartilage
      in osteoarthritis involves degradation of the extracellular matrix macromolecules
      and decreased expression of chondrocyte proteins necessary for normal joint
      function. Osteoarthritic cartilage often exhibits increased amounts of type I
      collagen and synthesis of proteoglycans characteristic of immature cartilage. The
      shift in cartilage phenotype in response to altered load yields a matrix that
      fails to support normal joint function. Mathematical modeling and experimental
      studies in animal models confirm an association between altered loading of
      diarthrotic joints and arthritic changes. Both types of studies implicate shear
      forces as a critical component in the destructive profile. The severity of
      cartilage destruction in response to altered loads appears linked to expression
      of biological factors influencing matrix integrity and cellular metabolism.
      Determining how shear stress alters chondrocyte metabolism is fundamental to
      understanding how to limit matrix destruction and stimulate cartilage repair and
      regeneration. At present, the precise biochemical and molecular mechanisms by
      which shear forces alter chondrocyte metabolism from a normal to a degenerative
      phenotype remain unclear. The results presented here address the hypothesis that
      articular chondrocyte metabolism is modulated by direct effects of shear forces
      that act on the cell through mechanotransduction processes. The purpose of this
      work is to develop critical knowledge regarding the basic mechanisms by which
      mechanical loading modulates cartilage metabolism in health and disease. This
      presentation will describe the effects of using fluid induced shear stress as a
      model system for stimulation of articular chondrocytes in vitro. The fluid
      induced shear stress was applied using a cone viscometer system to stimulate all
      the cells uniformly under conditions of minimal turbulence. The experiments were
      carried using high-density primary monolayer cultures of normal and
      osteoarthritic human and normal bovine articular chondrocytes. The analysis of
      the cellular response included quantification of cytokine release, matrix
      metalloproteinase expression and activation of intracellular signaling pathways.
      The data presented here show that articular chondrocytes exhibit a dose- and time
      dependent response to shear stress that results in the release of soluble
      mediators and extracellular matrix macromolecules. The data suggest that the
      chondrocyte response to mechanical stimulation contributes to the maintenance of
      articular cartilage homeostasis in vivo.

PMID- 10912183
TI  - Chondrocyte integrin expression and function.
AB  - The extracellular matrix (ECM) is an "information rich" environment and
      interactions between the chondrocyte and ECM regulate many biological processes
      important to cartilage homeostasis and repair including cell attachment, growth,
      differentiation, and survival. The integrin family of cell surface receptors
      appears to play a major role in mediating cell-matrix interactions that are
      important in regulating these processes. Chondrocytes have been found to express
      several members of the integrin family which can serve as receptors for
      fibronectin (alpha 5 beta 1), types II and VI collagen (alpha 1 beta 1, alpha 2
      beta 1, alpha 10 beta 1), laminin (alpha 6 beta 1), and vitronectin and
      osteopontin (alpha V beta 3). Integrin expression can be regulated by growth
      factors including IGF-I and TGF-beta. By providing a link between the ECM and the
      cytoskeleton, integrins may be important transducers of mechanical stimuli.
      Integrin binding stimulates intracellular signaling which can affect gene
      expression and regulate chondrocyte function. Further studies are needed to more
      clearly define the role of integrins in cartilage.

PMID- 10912184
TI  - Phenotypic modulation of nasal septal chondrocytes by cytoskeleton modification.
AB  - The reversion to the initial round shape of chondrocytes in monolayer cultures is
      one of the initial events required for the expression of cartilage-specific
      macromolecules. Thus, considerable research efforts have focused on developing
      reliable procedures to maintain a round morphology of cultured chondrocytes. Our
      study focuses on evaluating the response of dedifferentiated fetal rat
      chondrocytes to cytochalasin D, an actin-disrupting agent, with special emphasis
      on the morphological events. Immediately after exposure to the drug, cells round
      up but flatten again after removing the agent. However, immunocytochemical
      procedures revealed a disorganization of microfilaments and intermediate
      filaments. Phase-contrast and scanning electron microscopic observations revealed
      that on day 6 of culture, cells located at the top of the cell layer adopted a
      spherical morphology. Prominent differences were noted in control cultures where
      cells had to aggregate prior to overt chondrogenesis. These morphological changes
      occurred parallel to the expression of type II collagen, marker of the
      chondrocytes phenotype, strongly expressed in experimental cultures, but
      relatively weak in control cultures, and only restricted on areas of polygonal
      cellular aggregates. Furthermore, [35S]-sulphate incorporation into sulphated
      glycosaminoglycans increased rapidly with the period of culture to a maximum
      after 7 days and was then two-fold in treated cultures. Taken together, these
      findings indicated that cytochalasin-D stimulates chondrogenesis in response to
      modification of cytoskeleton architecture and the subsequent rounding up of the
      cells.

PMID- 10912185
TI  - The role of chondrocyte-matrix interactions in maintaining and repairing
      articular cartilage.
AB  - Throughout life chondrocytes maintain the articular cartilage matrix by replacing
      degraded macromolecules and respond to focal cartilage injury or degeneration by
      increasing local synthesis activity. These observations suggest that mechanisms
      exist within articular cartilage that stimulate chondrocyte anabolic activity in
      response to matrix degradation or damage. An important cartilage anabolic factor,
      insulin-like growth factor I (IGF-I), appears to have a role in stimulating
      chondrocyte anabolic activity. Although IGF-I is ubiquitous, its bioavailability
      is controlled by a class of secreted proteins, IGF binding proteins (IGFPBs). Of
      the six known IGFPBs, IGFBP-3 is the most abundant in human articular cartilage.
      We recently found that with increasing age, articular chondrocytes increase their
      expression of IGFBP-3. This observation led us to investigate the potential role
      of IGFBP-3 in chondrocyte-matrix interactions. Using immunofluorescent staining
      and confocal microscopy we found that IGFBP-3 accumulates with increasing age in
      the chondrocyte territorial matrix where it co-localizes with fibronectin, but
      not with tenascin-C or type VI collagen. Using purified proteins we demonstrated
      that IGFBP-3 binds to fibronectin in a dose dependent manner, but not to tenascin
      C. In vitro studies showed that IGFBP-3 alone inhibited chondrocyte synthetic
      activity while intact fibronectin alone significantly stimulated activity. When
      fibronectin and IGFBP-3 were combined we found that the inhibitory activity of
      low concentrations of IGFPB-3 was enhanced. These observations indicate that in
      mature articular cartilage IGF-I is stored in the chondrocyte territorial matrix
      through binding to a complex of IGFPB-3 and intact fibronectin. Storage of IGF-I
      of the territorial matrix may help maintain a relatively constant level of
      available IGF-I and the local increase in matrix synthesis following matrix
      damage may result from release of IGF-I. This mechanism may have an important
      role in maintaining and repairing articular cartilage and failure of this
      mechanism may lead to progressive articular cartilage degeneration.

PMID- 10912186
TI  - Modulation of the mechanical properties of tissue engineered cartilage.
AB  - Cartilaginous constructs have been grown in vitro using chondrocytes,
      biodegradable polymer scaffolds, and tissue culture bioreactors. In the present
      work, we studied how the composition and mechanical properties of engineered
      cartilage can be modulated by the conditions and duration of in vitro
      cultivation, using three different environments: static flasks, mixed flasks, and
      rotating vessels. After 4-6 weeks, static culture yielded small and fragile
      constructs, while turbulent flow in mixed flasks induced the formation of an
      outer fibrous capsule; both environments resulted in constructs with poor
      mechanical properties. The constructs that were cultured freely suspended in a
      dynamic laminar flow field in rotating vessels had the highest fractions of
      glycosaminoglycans and collagen (respectively 75% and 39% of levels measured in
      native cartilage), and the best mechanical properties (equilibrium modulus,
      hydraulic permeability, dynamic stiffness, and streaming potential were all about
      20% of values measured in native cartilage). Chondrocytes in cartilaginous
      constructs remained metabolically active and phenotypically stable over prolonged
      cultivation in rotating bioreactors. The wet weight fraction of
      glycosaminoglycans and equilibrium modulus of 7 month constructs reached or
      exceeded the corresponding values measured from freshly explanted native
      cartilage. Taken together, these findings suggest that functional equivalents of
      native cartilage can be engineered by optimizing the hydrodynamic conditions in
      tissue culture bioreactors and the duration of tissue cultivation.

PMID- 10912187
TI  - The influence of mechanical loading on isolated chondrocytes seeded in agarose
      constructs.
AB  - Articular cartilage is subjected to dynamic compressive loading during normal
      activity which influences chondrocyte metabolism through various
      mechanotransduction pathways. A well characterised and reproducible model system,
      involving chondrocytes embedded in agarose gel, has been used to investigate the
      effects of mechanical compression on chondrocytes, isolated from full depth
      cartilage or separately from the superficial and deep zone tissue. The role of
      nitric oxide as a mediator of mechanical-induced effects has also been studied.
      Chondrocytes were isolated, separately, from full depth, superficial and deep
      zone cartilage and seeded in 3% agarose constructs. Dynamic compressive strain
      was applied to the constructs using a range of frequencies (0.3, 1 and 3 Hz).
      Glycosaminoglycan synthesis, cell proliferation and nitrite production were
      assessed. In further experiments, constructs were compressed in the presence of 1
      mM L-NAME or 10 microM dexamethasone. Glycosaminoglycan synthesis by full depth
      chondrocytes was affected by compressive strain in a frequency dependent manner.
      Dynamic strain at all frequencies induced an increase in [3H]-thymidine
      incorporation. Glycosaminoglycan synthesis by deep zone cells was affected by the
      strain regimes in a similar fashion to full depth cells, while superficial cells
      exhibited a similar proliferative response to full depth cells. Dynamic
      compression inhibited nitrite production, the effect being reversed by L-NAME.
      Compression induced stimulation of [3H]-TdR incorporation was reversed by L-NAME.
      These studies demonstrate that glycosaminoglycan synthesis and proliferation are
      influenced by the dynamic strain regimes in a distinct manner. Indeed the data
      suggest that these processes occur in different chondrocyte sub-populations. It
      may be speculated that nitric oxide acts as a mediator of mechanotransduction
      processes affecting proliferation primarily in the superficial cell sub
      population.

PMID- 10912188
TI  - Articular cartilage repair: problems and perspectives.

PMID- 10912189
TI  - The role of 3D-microscopy in the study of chondrocyte-matrix interaction
      (alginate bead or sponge, rat femoral head cap, human osteoarthritic cartilage)
      and pharmacological application.
AB  - The potentialities of a new non-invasive optical scanning microscopy technique
      were evaluated through 3D analysis of chondrocyte-matrix interactions. Five
      different 2D or 3D culture systems were used: (1) MonoLayer (ML) of human
      chondrosarcoma cell line; (2) rat or human chondrocytes encapsulated in Alginate
      Bead (AB); (3) human chondrocytes encapsulated in Alginate Sponge (AS); (4) Rat
      Femoral Head Cap (RFHC); (5) slices of knee human Osteoarthritic Cartilage
      (HOAC). Chondrocytes ML, AB, RFHC were incubated for 24 h in vitro in the
      presence of recombinant human interleukin1-beta (rhIL1-beta) and the effects on
      cytoskeleton organisation (F-actin filament), Focal Adhesion Kinase (FAK)
      expression (tyrosine kinase), collagenase B expression (metalloprotease) were
      studied. Furthermore, the production of intracellular IL1-beta by LPS- or rhIL1
      beta-stimulated chondrocytes was shown to be partly suppressed by rhein (active
      metabolite of diacerhein) in all culture systems. This high resolution light
      microscopy gave complementary information that could be important for a better
      understanding of the interaction of chondrocytes with the extracellular matrix in
      a variety of culture devices.

PMID- 10912190
TI  - Effects of diacerein on biosynthesis activities of chondrocytes in culture.
AB  - The maintenance of articular cartilage integrity requires a balance between
      anabolic and catabolic processes which are under the control of chondrocytes.
      These cells are living in an anaerobic environment and normally do not divide.
      They are responsible for the continuous maintenance of the cartilage
      extracellular matrix (ECM). Although multiple factors are involved in the dynamic
      homeostasis of cartilage, increases in cytokines such as interleukin-1 (IL-1) are
      associated with a decrease in synthesis and an increase in degradation of the
      proteoglycans and collagens. Conversely, growth factors such as transforming
      growth factor-beta (TGF-beta) stimulate chondrocyte synthesis of collagens and
      proteoglycans, and reduce the activity of IL-1 stimulated metalloproteases, thus
      opposing the inhibitory and catabolic effects of IL-1. By its capability to
      reduce IL-1 effects and to stimulate TGF-beta expression in cultured articular
      chondrocytes, diacerein could favour anabolic processes in the OA cartilage and,
      hence may contribute to delay the progression of the disease.

PMID- 10912191
TI  - Present perspectives on cartilage and chondrocyte mechanobiology.
AB  - The focus of work on mechanotransduction in cartilage has changed markedly over
      the last 10 years. At the beginning of the decade, the interest lay in
      determining the net response of cartilage plugs, almost always as 35S-sulphate or
      3H-proline incorporation, to a variety of external loads, with the focus on
      whether changes in frequency in particular would stimulate or inhibit
      proteoglycan and protein synthesis [9,21]. Over the past few years the emphasis
      has shifted; it is now based mainly at the level of the cell as illustrated in
      Fig. 1. Here we will present a brief overview of the work presented at this
      symposium in light of these changes in approach.

PMID- 10912192
TI  - Measuring outcome in neurosurgery.

PMID- 10912193
TI  - Spinal neurenteric cysts without associated malformations. Are they the same as
      those presenting in spinal dysraphism?
AB  - Spinal neurenteric cysts are rare intradural developmental lesions, usually
      composed of a thin-walled cyst whose lining mimicks gastro-intestinal or
      respiratory epithelium. A detailed review of the literature revealed 80 cases of
      solitary spinal neurenteric cysts (including a new case of ours), which were
      analysed and compared, regarding clinical and pathological aspects, with 56 such
      cases of those with concomitant evidence of dysraphism. Older age and cervical
      location were found to be statistically characteristic of the solitary cysts in
      contrast to younger age and lumbosarcal location for the 'dysraphic' cases.
      Magnetic resonance imaging is the diagnostic modality of choice. Good evidence of
      the developmental origin of incomplete separation of notochord and endoderm was
      given by the fact that histologically solitary cysts were mainly composed by
      endodermal derivatives, while 'dysraphic' had also mesenchymal and ectodermal
      elements. Thus, it seems that additional spinal dysraphic changes are more likely
      to be found when ectodermal and mesenchymal elements co-exist with endodermal
      ones, possibly indicating an earlier error in development than in other cases
      containing only endodermal elements.

PMID- 10912194
TI  - Assessing outcome in lumbar disc surgery using patient completed measures.
AB  - Measuring outcome after spinal surgery is difficult. The objective of this study
      was to assess the use of four measures in establishing outcome in patients
      undergoing lumbar discectomy. Forty-six consecutive patients who had undergone
      two operations for lumbar disc prolapse and 54 patients who had undergone one
      operation for the same condition over the same period were identified. The SF-36
      questionnaire was used to assess general health. The Roland-Morris questionnaire
      and a simple modification of the Roland-Morris questionnaire were used to assess
      back and leg related disability, respectively. Analogue pain scales were used to
      measure back pain and sciatica. The SF-36 scores revealed significantly worse
      health status in the two operation compared with the one operation patients and
      in all patients compared with the normal population. Using the Roland-Morris and
      the leg disability questionnaires, patients who had undergone two operations
      reported significantly worse disability (Roland-Morris, 53%, poor outcome) than
      those who had undergone one operation (Roland-Morris, 19%, poor outcome). There
      was significantly greater back disability than leg disability in both groups of
      patients and this was confirmed by the analogue pain scales. In patients who had
      undergone two operations, 25% classified their back pain as very bad or
      unbearable, and 22.5% described very bad or unbearable leg pain. For the one
      operation patients these figures were 9.5 and 2.4%, respectively. The results
      demonstrate that both generic and condition specific patient completed measures
      have the potential to detect differences in outcome between patients who have
      undergone either one or two lumbar disc operations. The study provides support
      for the use of these patient completed measures in assessing outcome in lumbar
      disc surgery.

PMID- 10912195
TI  - Split cord malformations in myelomeningocele patients.
AB  - Split cord malformations (SCMs) may occur in conjunction with myelomeningoceles,
      and are often ignored or misdiagnosed, potentially causing spinal cord tethering.
      In this paper, we study the incidence and clinical significance of such an
      association. We have retrospectively reviewed the medical records and radiographs
      of 20 myelomeningocele patients who had a SCM. These comprised at least 6% of our
      myelomeningocele patients. Five of the 20 had simultaneous repair of both lesions
      at birth. The other 15 were diagnosed with the SCM in a delayed fashion (mean age
      4.4 years). Clinical presentations that prompted a diagnostic investigation
      included hypertrichosis (1), pain (2), routine radiographic follow-up (2),
      neurourological deterioration (10) and progressive scoliosis (5). In 17 of the 20
      patients, the SCM involved the placode or was within one level of it. Fifteen of
      these were in the area of the placode or one segment above it. Five of the 20
      patients had hypertrichosis and 15 of the 20 patients had a bony midline septum
      (i.e. type I SCM). Several accompanying spinal dysraphic lesions also contributed
      to the tethering: thickened (previously inconspicuous) filum terminale (6),
      syringohydromyelia (5) and a neurenteric cyst with a benign teratoma (1).
      Arachnoiditis secondary to the prior myelomeningocele repair was found, as
      expected, in all 15 patients. However, in virtually all patients, there was also
      evidence of tethering at the level of the SCM. Long-term follow-up showed
      stabilization of preoperative symptoms and signs, whereas complications of the
      operation and clinical evidence of retethering were uncommon. Myelomeningocele
      patients should be screened with clinical examinations looking for hypertrichosis
      and with spinal radiographs preoperatively looking for evidence of SCM (bony
      midline septum and/or interpedicular widening not due to the myelomeningocele).
      Intraoperatively, the placode and the rostral spinal cord segment should be
      carefully inspected for an SCM and other dysraphic lesions.

PMID- 10912196
TI  - Post operative supplementary motor area syndrome: clinical features and outcome.
AB  - The syndrome of the supplementary motor area (SMA) is not well recognized and its
      features can easily be confused with pyramidal weakness. The authors describe the
      SMA syndrome in six patients who underwent surgery for tumours located in the
      SMA, three in the dominant and three in the non-dominant hemispheres. All of them
      underwent complete resection of the anatomically described SMA, with partial (n =
      4) or total resection (n = 2) of the tumour. In the postoperative period, all
      these patients exhibited reduction of spontaneous movements and difficulty in
      performing voluntary motor acts to command in the contralateral limbs, although
      the tone in the limbs was maintained or increased. The function of these limbs in
      serial automatic motor activities (for example, dressing and walking) was,
      however, relatively unaffected. Speech deficits were seen in only one of three
      patients with the dominant SMA syndrome. Besides a severe impairment of
      volitional movements, the salient features of the deficits in this syndrome are
      hemineglect and dyspraxia or apraxia involving the contralateral limbs. All
      patients recovered their motor functions over varying periods of time ranging
      from one to a few weeks. Long-term follow-up (median 24 months) in five patients
      revealed complete return of function in the affected limbs. It is important to
      recognize the entity of the SMA syndrome and differentiate it from the deficits
      that result from operative damage to the motor cortex as the deficits associated
      with the former are likely to recover almost completely over a short period of
      time.

PMID- 10912197
TI  - Experience with neurocysticercosis in the UK: correct diagnosis and neurosurgical
      management of the small enhancing brain lesion.
AB  - Neurocysticercosis is a major cause of epilepsy and other neurological morbidity
      in endemic areas of the world but is exceptionally rare in the West. We have
      recently had experience of eight patients with this condition, seven presenting
      with epilepsy and single or multiple small, enhancing parenchymal lesions and one
      with hydrocephalus caused by a midbrain lesion. One lesion was stereotactically
      excised after it persisted, but in five other cases spontaneous cyst resolution
      was observed during expectant management with anticonvulsants. Two patients with
      multiple lesions were referred to us for further management but were free of
      active infection. Recent studies show that neurocysticercosis may often be
      diagnosed based upon the clinical, epidemiological and radiological features.
      Spontaneous cyst resolution is to be expected in this condition and suspected
      patients should be carefully observed and surgery avoided. We believe that this
      disease presents more commonly than has been appreciated in the UK and propose a
      protocol for management.

PMID- 10912198
TI  - Head injury in the severely injured: long-term follow-up in 157 patients.
AB  - Ninety-two patients with head injury in the context of multiple injury were
      followed up 5 years after injury. Severe disability in this group of patients was
      nearly always due to brain/spinal cord injury, rather than musculoskeletal
      injury. A substantial number of patients with mild or moderate head injuries had
      significant persisting disability 5 years after injury.

PMID- 10912199
TI  - Giant intradiploic epidermoid cysts of the skull. A report of eight cases.
AB  - Giant intradiploic epidermoid cyst of the skull is a rare tumour. Only a small
      number of cases have been reported. Over a 16-year period, we treated eight cases
      of giant intradiploic epidermoid cyst of the skull. All cases were between 19 and
      45 years of age, except one aged of 61 years. Five cases presented with local
      swellings, three patients came with infection and one had an extradural abscess.
      All the patients were operated upon after adequate preoperative care. Patients
      with infection required appropriate antibiotics. Total or near total excision was
      carried out in all. One patient developed postoperative infection. So for those
      have been no recurrences. This appears to be the largest series of giant
      intradiploic epidermoid cyst of the skull so far reported.

PMID- 10912200
TI  - Studies of regional subdural pressure gradients during craniotomy.
AB  - We investigated subdural pressure gradients within the operative field of the
      exposed intact dura in 53 patients with space-occupying lesions during
      craniotomy. In 37 patients with supratentorial brain tumour paired measurements
      of subdural pressure were studied in either the same horizontal or vertical
      plane. In 16 patients with infratentorial brain tumours the influence of a tumour
      was studied by measuring subdural pressure bilaterally over the right and left
      cerebellar hemisphere. Significant correlation between the vertical distance and
      the difference in subdural pressure was found, with the highest pressure in the
      most downward part of the brain. In patients with tumour in one cerebellar
      hemisphere, subdural pressure ipsilateral to the tumour was significantly higher
      than the subdural pressure on the contralateral side. The present study
      demonstrates subdural pressure gradients within the area of the exposed dura. The
      subdural pressure was influenced by the underlying tumour and/or gravity. This
      must be taken into consideration when a dura incision is made.

PMID- 10912201
TI  - Neurosurgery in Victoria, Australia: training and practice compared with the
      United Kingdom.
AB  - In the UK there are currently great changes taking place in both higher surgical
      training and consultant practice. Australia inherited the British system, many
      aspects of which it retains, but has moved to a US type training programme.
      Recent experience of British and Australian neurosurgical practice allows useful
      comparisons to be made with possible benefit to both. Neurosurgery in Australia
      is a more consultant based service than that in the UK, with 73 consultants for a
      population of 18 million. Consultants work primarily from their private rooms and
      consultant numbers in the public sector are misleading as few of them approach
      full time. Neurosurgical training is organized on a national basis with a finite
      training programme. This consists of a rotation of different jobs supplemented by
      consultant led lectures and tutorials. Training is regularly monitored, with a
      final exit examination. The disadvantages are the relative lack of operating
      whilst training, many neurosurgeons becoming accredited with the personal
      operating experience expected of a British registrar; and the working hours; most
      trainees work 1 in 1, which precludes any sort of normal family life. In summary,
      the relative strengths of the British and Australian systems are largely
      complementary, there being ample scope for each to learn from the other.

PMID- 10912202
TI  - Subdural air limits the elicitation of compound muscle action potentials by high
      frequency transcranial electrical stimulation.
AB  - High-frequency transcranial electrical stimulation was performed in 8 patients
      undergoing surgery in the sitting position. Following the opening of the dura of
      the posterior fossa changes in compound muscle action potentials were observed.
      These changes were not attributable to surgical manoeuvres at the brain stem or
      spinal cord, or to anaesthetic changes. In all these cases intraoperative
      fluoroscopy of the skull revealed a subdural air collection underneath the
      stimulation electrodes. Such a subdural air collection, not infrequent in
      patients operated on in the sitting position, limits the application of high
      frequency transcranial electrical stimulation as a monitoring technique. It
      remains unclear if this effect is due to the increasing distance between scalp
      and cortex and the insulating effect of subdural air, or due to displacement of
      the motor cortex. The practical importance of this report is derived from the
      increasing application of intraoperative motor pathway monitoring.

PMID- 10912203
TI  - Distal superior cerebellar artery aneurysm.
AB  - A case of an aneurysm arising from the distal portion of the superior cerebellar
      artery is described. Angiography showed an aneurysm near the internal auditory
      canal, arising from the medial branch of the superior cerebellar artery
      associated with hypoplasia of the ipsilateral anterior inferior cerebellar artery
      and posterior inferior cerebellar artery.

PMID- 10912204
TI  - Brain abscess decades after a penetrating shrapnel injury.
AB  - We describe a patient who developed a brain abscess 52 years after sustaining a
      penetrating craniocerebral shrapnel injury. For 10 years he had suffered from
      diabetes mellitus, a disorder known to predispose to infections from a diminished
      body defence. The treatment and aetiology of this rare occurrence is discussed.

PMID- 10912205
TI  - Enterogenous cyst of the posterior fossa.
AB  - We report the case of a 13-year-old boy who presented with deafness due to a
      posterior fossa cystic lesion which was surgically excised. Histological
      examination showed it to be an enterogenous cyst. These extremely rare lesions
      seldom occur within the neural axis.

PMID- 10912206
TI  - Primary spinal germinoma in a patient with concomitant Klinefelter's syndrome.
AB  - It is known that patients with Klinefelter's syndrome are inclined to develop
      concomitant malignant tumours, as well as extragonadal germ cell tumours. The
      association of a primary spinal germinoma in a patient with Klinefelter's
      syndrome is reported for the first time, and the coincidence of elevated
      gonadotropin levels and oncogenesis is discussed.

PMID- 10912207
TI  - Intraparenchymal pericatheter cyst. A rare complication of ventriculoperitoneal
      shunt for hydrocephalus.
AB  - Intraparenchymal pericatheter cyst is rarely reported. Obstruction in the
      ventriculoperitoneal shunt leads to recurrence of hydrocephalus, signs of raised
      intracranial pressure and possibly secondary complications. Blockage of the
      distal catheter can result, unusually, in cerebrospinal fluid oedema and/or
      intraparenchymal cyst around the ventricular catheter which may produce focal
      neurological deficit. We report two cases of distal catheter obstruction with
      formation of cysts causing local mass effect and neurological deficit. Both
      patients had their shunt system replaced, which led to resolution of the cyst and
      clinical improvement. One patient had endoscopic exploration of the cyst which
      confirmed the diagnosis made on imaging studies. Magnetic resonance imaging was
      more helpful than computed tomography in differentiating between oedema and
      collection of cystic fluid. Early recognition and treatment of pericatheter cyst
      in the presence of distal shunt obstruction can lead to complete resolution of
      symptoms and signs.

PMID- 10912208
TI  - Maxillofacial-transclival juxtabasilar penetrating butcher's knife injury: a case
      report.
AB  - A 90-year-old woman presented with an accidental maxillofacial-clival penetrating
      injury with a butcher's knife, with its tip reaching the immediate proximity of
      the basilar artery. The knife was removed at surgery, with no untoward sequelae.

PMID- 10912209
TI  - Cerebellopontine angle medulloblastoma.

PMID- 10912210
TI  - Ganglioneuroblastoma of the cauda equina.
AB  - A 39-year-old lady presented with low back pain and neurogenic claudication.
      Magnetic resonance imagining revealed an intradural neoplasm in the cauda equina
      region. The patient underwent lumbar laminectomy and total excision of the
      neoplasm. Biopsy showed it to be a ganglioneuroblastoma, which is rare in the
      spinal canal and so far does not appear to have been reported in the region of
      the cauda equina. Its management is discussed.

PMID- 10912211
TI  - Upward migration of peritoneal catheter.

PMID- 10912212
TI  - Sudden unexplained death in psychiatric in-patients.

PMID- 10912213
TI  - Population research and mental health policy. Bridging the gap.

PMID- 10912214
TI  - Compensations for brain deficits. "Every cloud...".

PMID- 10912215
TI  - Treatment interventions and findings from research: bridging the chasm in child
      psychiatry.
AB  - BACKGROUND: Along with all other branches of medicine, child and adolescent
      psychiatry is faced with the need to consider its evidence base and justify its
      activities accordingly. AIMS: To consider critically the use of the term
      'evidence', to suggest limits to the value of conventionally defined evidence and
      to point to possible ways forward to bridge the gap between research findings and
      clinical practice. METHOD: A review of the literature relating to the use of
      evidence-based methods. RESULTS: The term 'evidence' needs to be used more widely
      than is conventionally the case. Substantial evidence exists from controlled
      trials, but there are barriers to its use. CONCLUSIONS: A move away from
      nonvalidated methods of intervention is both desirable and feasible. The use of
      qualitative methods of enquiry, both in situations where controlled trials are
      unlikely to be feasible and as adjuncts to quantitative methods, should be
      considered more seriously.

PMID- 10912216
TI  - Meta-analysis of randomised controlled trials of fluoxetine v. placebo and
      tricyclic antidepressants in the short-term treatment of major depression.
AB  - BACKGROUND: Previous meta-analyses of fluoxetine as an antidepressant have many
      methodological problems, including diagnosis of major depression, validity of
      outcome measures and lack of intention-to-treat analyses. AIMS: To provide an
      estimate of the effect of fluoxetine compared with placebo and tricyclic
      antidepressants (TCAs), and to investigate reasons for early discontinuation from
      acute treatment. METHOD: Randomised trials were analysed using both intention-to
      treat, efficacy and end-point. RESULTS: Fluoxetine was superior to placebo but
      effect size was low. In trials comparing fluoxetine v. TCA, the results for all
      trials and for the USA trials showed a trend in favour of fluoxetine. Those for
      the non-USA trials showed a trend in favour of TCA. When combined, the results
      showed that significantly fewer patients on fluoxetine discontinued treatment
      because of adverse events. CONCLUSION: Fluoxetine is superior to placebo,
      irrespective of the analytical approach use, whereas the results obtained v. TCAs
      depend on the approach used. Hence, the results should be interpreted in this
      light.

PMID- 10912217
TI  - Sixteen-year mortality in patients with affective disorder commenced on lithium.
AB  - BACKGROUND: Lithium treatment is claimed to reduce mortality in patients with
      affective disorder, but the evidence is conflicting. AIM: To estimate mortality
      rates from a cohort of patients with affective disorder commenced on lithium with
      an observation period of two years and a follow-up after 16 years. METHOD: The
      mortality rates of patients were compared with those of the general Danish
      population, standardised for age, gender and calendar time with respect to death
      from all causes, suicide and death from cardiovascular disease. RESULTS: Forty of
      the study's 133 patients died during the 16-year observation period (11 from
      suicide). Mortality among patients commenced on lithium was twice that of the
      general population. The statistically significantly elevated mortality was due
      largely to an excess of suicides; mortality from all other causes was similar to
      the background populations. Thirty-two patients died after the first two years of
      observation and were included in the analysis of the association between death
      and treatment compliance. Suicide occurred more frequently among those patients
      not complying with treatment. CONCLUSION: Mortality, especially suicide, was
      significantly increased in unselected patients with affective disorder commenced
      on lithium relative to the general population.

PMID- 10912218
TI  - Complementary approaches to the assessment of personality disorder. The
      Personality Assessment Schedule and Adult Personality Functioning Assessment
      compared.
AB  - BACKGROUND: Current concepts and measures of personality disorder are in many
      respects unsatisfactory. AIMS: To establish agreement between two contrasting
      measures of personality disorder, and to compare subject-informant agreement on
      each. To examine the extent to which trait abnormality can be separated from
      interpersonal and social role dysfunction. METHOD: Fifty-six subjects and their
      closest informants were interviewed and rated independently. Personality
      functioning was assessed using a modified Personality Assessment Schedule (M
      PAS), and the Adult Personality Functioning Assessment (APFA). RESULTS: Subject
      informant agreement on the M-PAS was moderately good, and agreement between the M
      PAS and the APFA, across and within subjects and informants, was comparable to
      that for the M-PAS. This was equally the case when M-PAS trait plus impairment
      scores and trait abnormality scores were used. CONCLUSIONS: The M-PAS and the
      APFA are probably assessing similar constructs. Trait abnormalities occur
      predominantly in an interpersonal context and could be assessed within that
      context.

PMID- 10912219
TI  - How mental illness is portrayed in children's television. A prospective study.
AB  - BACKGROUND: There are no published studies concerning the depiction of mental
      illness in children's television programmes. AIMS: To determine whether mental
      illness was depicted in children's television. METHOD: Sample of one complete
      week of children's television (57 hours, 50 minutes; 128 series episodes: 69
      cartoon animations, 12 non-cartoon animations, 47 real life) provided for
      children under the age of 10 years. Disclosure analysis of portrayals of mental
      illness through repeated viewings identified patterns in the use of linguistic,
      semiotic and rhetorical resources. RESULTS: Of the 128 episodes, 59 (46%)
      contained one or more references to mental illness, predominantly in cartoons (n
      = 47, 80%) compared with other episode types (chi 2 = 17.1, d.f. = 2, P < 0.05).
      Commonly occurring terms such as 'crazy' (n = 28), 'mad' (n = 19) and 'losing
      your mind' (n = 13) were employed to denote loss of control. The six consistently
      mentally ill characters were almost entirely devoid of admirable attributes.
      CONCLUSION: Young viewers are being socialized into stigmatizing conceptions of
      mental illness.

PMID- 10912220
TI  - Camberwell Assessment of Need for the Elderly (CANE). Development, validity and
      reliability.
AB  - BACKGROUND: There exists no instrument specifically designed to measure
      comprehensively the needs of older people with mental disorders. AIM: To develop
      such an instrument which would take account of patients', staff and careers'
      views on needs. METHOD: Following an extensive development process, the
      assessment instrument was subjected to a test-retest and interrater reliability
      study, while aspects of validity were addressed both during development and with
      data provided by sites in the UK, Sweden and the USA. RESULTS: The Camberwell
      Assessment of Need for the Elderly (CANE) comprises 24 items (plus two items for
      career needs), and records staff, career and patient views. It has good content,
      construct and consensual validity. It also demonstrates appropriate criterion
      validity. Reliability is generally very high: kappa > 0.85 for all staff ratings
      of interrater reliability. Correlations of interrater and test-retest reliability
      of total numbers of needs identified by staff were 0.99 and 0.93, respectively.
      CONCLUSIONS: The psychometric properties of the CANE seem to be highly
      acceptable. It was easily used by a wide range of professionals without formal
      training.

PMID- 10912221
TI  - Three-year prognosis of depression in the community-dwelling elderly.
AB  - BACKGROUND: Depression is the most common mental disorder in the community
      dwelling elderly. AIMS: To determine the three-year prognosis of depression in a
      cohort of 127 community-dwelling elderly subjects and identify factors relevant
      to outcome. METHOD: The subjects, diagnosed depressed at year 0 using the GMS
      AGECAT package, were followed up three years later. A number of factors were
      investigated for an association with recovery from, or persistence of,
      depression. RESULTS: At follow-up, 30.2% of the depressed subjects had died,
      34.9% had persistent or relapsed case-level depression, 24.5% had other case- or
      sub-case-level mental illness and 10.4% had recovered completely. Physical ill
      health, bereavement and positive family history of depression were associated
      with poor outcome, whereas treatment with antidepressant medication significantly
      improved prognosis. CONCLUSIONS: Late-life depression in community-dwelling
      subjects is a chronic condition. However, the positive response to antidepressant
      medication suggests that it should be vigorously treated.

PMID- 10912222
TI  - Functional correlates of musical and visual ability in frontotemporal dementia.
AB  - BACKGROUND: The emergence of new skills in the setting of dementia suggests that
      loss of function in one brain area can release new functions elsewhere. AIMS: To
      characterise 12 patients with frontotemporal dementia (FTD) who acquired, or
      sustained, new musical or visual abilities despite progression of their dementia.
      METHOD: Twelve patients with FTD who acquired or maintained musical or artistic
      ability were compared with 46 patients with FTD in whom new or sustained ability
      was absent. RESULTS: The group with musical or visual ability performed better on
      visual, but worse on verbal tasks than did the other patients with FTD. Nine had
      asymmetrical left anterior dysfunction. Nine showed the temporal lobe variant of
      FTD. CONCLUSION: Loss of function in the left anterior temporal lobe may lead to
      facilitation of artistic or musical skills. Patients with the left-sided temporal
      lobe variant of FTD offer an unexpected window into the neurological mediation of
      visual and musical talents.

PMID- 10912223
TI  - Low blood pressure and risk of depression in the elderly. A prospective community
      based study.
AB  - BACKGROUND: The relationship between depression and low blood pressure in
      unclear. AIMS: To examine the temporal relation between low blood pressure and
      depression in a two-year follow-up. METHOD: The study group consisted of 1389
      subjects aged 59-71 years; 1272 (92%) were examined after two years. Subjects
      completed the Center for Epidemiological Studies-Depression (CES-D) and the
      Spielberger inventory scales to assess depressive and anxiety symptoms
      respectively. Data were collected on socio-demographic characteristics, smoking
      and drinking habits, medical history, drug use and blood pressure measures.
      RESULTS: Among 1112 subjects who were considered as non-depressed at baseline,
      logistic regression models showed that low diastolic blood pressure (DBP) and
      decrease of blood pressure were predictors of high depressive symptomatology at
      follow-up. Baseline high CES-D scores did not predict low blood pressure two
      years after. CONCLUSIONS: In our study, low blood pressure was a risk factor for,
      but not a consequence of, high depressive symptomatology.

PMID- 10912224
TI  - APOE epsilon 4 influences the manifestation of Alzheimer's disease in adults with
      Down's syndrome.
AB  - BACKGROUND: Recent studies of the relationship between the apolipoprotein E
      (APOE) gene and Alzheimer's disease in adults with Down's syndrome have revealed
      inconsistent results. AIMS: To assess the role of the APOE gene in the
      manifestation of Alzheimer's disease in adults with Down's syndrome. METHOD: We
      studied the APOE genotypes of 24 adults with dementia and 33 non-demented adults
      with Down's syndrome over 35 years of age, and an additional group of 164 non
      learning disabled adults. We also carried out a meta-analysis of all previously
      published studies of association between APOE and Down's syndrome, incorporating
      the current data. RESULTS: We observed a non-significant excess of APOE epsilon 4
      and a reduction of epsilon 2 in adults with dementia compared with non-demented
      adults with Down's syndrome in our sample. However, meta-analysis showed a
      significantly higher frequency of epsilon 4 in adults with dementia compared with
      non-demented adults with Down's syndrome (odds ratio = 2.02, 95% CI 1.33-3.07, P
      = 0.001), but no significant reduction in the frequency of epsilon 2.
      CONCLUSIONS: The APOE epsilon 4 allele acts as a risk factor for the age-specific
      manifestation of Alzheimer's disease in people with Down's syndrome.

PMID- 10912225
TI  - Reliability and validity of the CANDID--a needs assessment instrument for adults
      with learning disabilities and mental health problems.
AB  - BACKGROUND: People with learning disabilities and mental health problems have
      complex needs. Care should be provided according to need. AIM: To develop a
      standardised needs-assessment instrument for adults with learning disabilities
      and mental health problems. METHOD: The Camberwell Assessment of Need for Adults
      with Developmental and Intellectual Disabilities (CANDID) was developed by
      modifying the Camberwell Assessment of Need (CAN). Concurrent validity was tested
      using the Global Assessment of Functioning (GAF) and the Disability Assessment
      Schedule (DAS). Test-retest and interrater reliability were investigated using 40
      adults with learning disabilities and mental health problems. RESULTS: CANDID
      scores were significantly correlated with both DAS (P < 0.05) and GAF scores (P <
      0.01). Correlation coefficients for interrater reliability were 0.93 (user), 0.90
      (career), and 0.97 (staff ratings); for test-retest reliability they were 0.71,
      0.69 and 0.86 respectively. Mean interview duration was less than 30 minutes.
      CONCLUSIONS: The CANDID is a brief, valid and reliable needs assessment
      instrument for adults with learning disabilities and mental health problems.

PMID- 10912226
TI  - Changing patterns in the use of the Mental Health Act 1983 in England, 1984-1996.
AB  - BACKGROUND: The Mental Health Act 1983 (MHA) is due to be revised by Parliament
      in the near future. AIMS: To explore changes in the use of the Act since its
      introduction. METHOD: The Department of Health and the Home Office routinely
      collect data on the numbers of patients admitted to psychiatric hospitals under
      the MHA. We present absolute figures, by year, for the total numbers admitted
      under each section of the Act. We used the total psychiatric hospital admissions
      and total prison populations as denominator data. RESULTS: Formal admissions rose
      from 16,044 in 1984 to 26,308 in 1996, a 63% increase. Admissions under the MHA
      have increased as a proportion of all admissions. The increase is mainly
      accounted for by changes in the use of Part II of the Act, in particular sections
      2 and 3. The use of forensic sections (Part III) has also increased, with a
      marked increase of sections 47 and 48. Use of Part X of the Act (sections 135 and
      136) declined in the late 1980s but rose again in the 1990s. CONCLUSIONS: Formal
      admissions are more common than they were in 1984, despite there being fewer
      psychiatric beds. This is probably due to changes in the provision of psychiatric
      services, and changing societal pressures on psychiatrists away from
      libertarianism and towards coercion.

PMID- 10912227
TI  - Cassel Personality Disorder Study. Methodology and treatment effects.
AB  - BACKGROUND: The effectiveness of hospital-based treatment models for personality
      disorder is still uncertain. AIMS: To compare effectiveness of two models of
      psychosocial intervention for personality disorder. METHOD: Two samples of people
      with personality disorder allocated to a one-stage treatment model (in-patient
      treatment with no after care) and to a two-stage model (shorter in-patient
      admission followed by outreach therapy) are prospectively compared. RESULTS:
      Subjects in the two-stage sample did significantly better on global assessment of
      mental health (according to the Global Assessment Score (GAS)) at 6 and 12 months
      and on social adjustment (according to the Social Adjustment Scale (SAS)) at 12
      months. Significant differences in rates of reliable improvement on the GAS (43%
      v. 17%) and SAS (39% v. 15%) in favour of the two-stage condition were found at
      12 months. Subjects with borderline personality disorder (BPD) allocated to the
      two-stage model improved significantly more than such patients in the one-stage
      model. CONCLUSIONS: A long-term phased model which combines hospital-based and
      community-based strategies has advantages over a purely in-patient model for the
      treatment of BPD.

PMID- 10912228
TI  - Comments on Jerusalem syndrome.

PMID- 10912229
TI  - Effectiveness of intensive treatment in severe mental illness.

PMID- 10912230
TI  - Antidepressant choice to minimise treatment resistance.

PMID- 10912231
TI  - Depression and interferon-alpha therapy.

PMID- 10912232
TI  - Sluggish economics affect health of Japanese 'business warriors'.

PMID- 10912233
TI  - Assessment and discharge following self-harm.

PMID- 10912234
TI  - Ambient iodine and lithium-associated with clinical hypothyroidism.

PMID- 10912235
TI  - Consent in mandatory homicide inquiries.

PMID- 10912236
TI  - Medical roles in mental health review tribunals.

PMID- 10912237
TI  - Possible neuroleptic malignant syndrome with quetiapine.

PMID- 10912238
TI  - Consultation on assessment of the health risk of dioxins; re-evaluation of the
      tolerable daily intake (TDI): executive summary.

PMID- 10912239
TI  - Exposure of populations to dioxins and related compounds.
AB  - The present situation with respect to the exposure of the general human
      population to PCDDs, PCDFs and (dioxin-like) PCBs and specific issues that should
      be taken into consideration for a risk assessment of these exposures have been
      summarized. The information is based on studies performed in The Netherlands and
      Germany in the last 10 years. Additional data have been collected through a
      literature search and through many contacts with researchers and national
      authorities. The most important route for human exposure to PCDDs, PCDFs and
      (dioxin-like) PCBs is food consumption contributing over 90% of total exposure,
      with products of animal origin and fish making the greatest contribution to this
      exposure. The dietary intake of PCDDs and PCDFs by the general population of
      industrialized countries is on average 1-3 picograms of (i)-TEQ per kilogram body
      weight per day. If the contribution of dioxin-like PCBs are also considered, the
      daily TEQ intake can be a factor of two to three higher. Special consumption
      habits and consumption of highly contaminated foodstuffs may lead to lower and
      higher TEQ intakes. In general, TEQ intake increases during childhood and
      stabilizes in adults of about 20 years of age. However, when normalized by body
      weight exposure is found to decrease with childhood age due to increasing body
      weight. Exposure has been shown to have fallen over time in all countries where
      data are available. Countries that started to implement measures to reduce dioxin
      emissions in the late 1980s, such as The Netherlands, United Kingdom and Germany,
      clearly show decreasing PCDD/PCDF and PCB levels in food and consequently a
      significantly lower dietary intake of these compounds by almost a factor of 2
      within the past 7 years.

PMID- 10912240
TI  - Mechanistic aspects--the dioxin (aryl hydrocarbon) receptor.
AB  - The Ah receptor mediates the toxicological responses of 2,3,7,8-TCDD and related
      compounds. Receptor-deficient animals were shown to be resistant to the toxic
      effects of dioxin, although there is also evidence for the existence of a
      receptor-independent pathway for dioxin-induced toxicity. In the cytosol the
      receptor is present in a non-activated ligand binding conformation. Association
      with Arnt in the nucleus turns the receptor complex into a ligand activated form.
      The physiological role of the receptor is not yet understood; however, the
      conservation of the receptor in a wide range of animal species (including humans)
      suggests a fundamental role in cellular physiology.

PMID- 10912242
TI  - Non-carcinogenic effects of TCDD in animals.
AB  - Exposure to TCDD and related chemicals leads to a plethora of effects in multiple
      species, tissues, and stages of development. Responses range from relatively
      simple biochemical alterations through overtly toxic responses, including
      lethality. The spectrum of effects shows some species variability, but many
      effects are seen in multiple wildlife, domestic, and laboratory species, ranging
      from fish through birds and mammals. The same responses can be generated
      regardless of the route of exposure, although the administered dose may vary. The
      body burden appears to be the most appropriate dosimetric. Many of the effects
      often attributed to TCDD are associated with relatively high doses: lethality,
      wasting, lymphoid and gonadal atrophy, chloracne, hepatotoxicity, adult
      neurotoxicity, and cardiotoxicity. Changes in multiple endocrine and growth
      factor systems have been reported in a manner which is tissue, sex, and age
      dependent. The most sensitive adverse effects observed in multiple species appear
      to be developmental, including effects on the developing immune, nervous, and
      reproductive systems. Such effects have been observed at maternal body burdens in
      the range of 30-80 ng/kg in both non-human primates and rodents. Biochemical
      effects on cytokine expression and metabolizing enzymes occur at body burdens
      which are within a factor of ten of the clearly adverse developmental responses.
      Thus, effects on the immune system, learning, and the developing reproductive
      system of multiple animals occur at body burdens which are close to those present
      in the background human population.

PMID- 10912241
TI  - Toxicokinetics.
AB  - The toxicokinetic determinants of dioxin and related chemicals depend on three
      major properties: lipophilicity, metabolism, and binding to CYP1A2 in the liver.
      The induction of CYP1A2 is partially under the control of the aryl hydrocarbon
      receptor (AhR). Lipophilicity increases with more chlorination and controls
      absorption and tissue partitioning. Metabolism is the rate-limiting step for
      elimination. Induction of CYP1A2 leads to hepatic sequestration of TCDD. Binding
      to this inducible hepatic protein results in non-linear dose-dependent tissue
      distribution: with increasing doses, the relative concentration in extra-hepatic
      tissues decreases while that in liver increases. The induction of this protein
      occurs in both animals and humans and results in an increase in the liver to fat
      ratio of these compounds. Humans have similar sensitivities to rodents for dioxin
      like compounds when using tissue concentration (from in vitro studies), body
      burden, average lifetime serum lipid concentration, or lifetime area-under-the
      curve concentration based on both low dose (biochemical) and high dose (cancer)
      driven endpoints. To reach the same tissue concentration in humans as rodents
      however, humans need a lower daily intake than rodents based on differences in
      pharmacokinetic behaviour. This clearly indicates that physiologically based
      pharmacokinetic models should be explored for the estimation of the daily intake
      of dioxin-like compounds in humans based on tissue dose levels or derivatives of
      those.

PMID- 10912243
TI  - Animal studies addressing the carcinogenicity of TCDD (or related compounds) with
      an emphasis on tumour promotion.
AB  - Dioxin and certain structurally related compounds increase the incidence of liver
      neoplasms in rodents upon chronic bioassay. Short-term studies indicate the lack
      of direct DNA-damaging effects including covalent binding to DNA; however,
      secondary mechanisms may be important in the observed carcinogenicity as these
      chemicals affect a number of pathways necessary for maintenance of normal growth
      control and differentiation status. Studies with TCDD in the mouse skin support a
      lack of initiating activity but an ability to promote the growth of previously
      initiated lesions indicative of a promoting agent. Mouse skin tumour promotion
      studies indicate that Ah receptor activation may be involved in promotion by TCDD
      and selected structurally related compounds. While the mechanism of
      carcinogenicity induced by TCDD is unknown, the processes involved have a no
      effect level, which in the rat liver is at an exposure level below 10 ng
      TCDD/kg/day. At least for the rodent liver, the relative effective dose for
      cytochrome P450 induction is not a good indicator of promotion potency. Studies
      on liver tumour promotion in the female rat liver support a non-genotoxic
      mechanism for the induction of neoplasms by TCDD. The ability of TCDD to enhance
      proliferation and inhibit apoptotic processes in focal hepatic lesions further
      supports an indirect mechanism of carcinogenicity.

PMID- 10912244
TI  - Human health effects after exposure to 2,3,7,8-TCDD.
AB  - In 1949, the first descriptions of human exposure to 2,3,7,8-tetrachlorodibenzo-p
      dioxin (2,3,7,8-TCDD)-contaminated chemicals were reported after a
      trichlorophenol reactor explosion in Nitro, West Virginia, USA. Reported non
      cancer health effects included a range of conditions affecting most systems.
      Additional reports of the health consequences of exposure continued through the
      remainder of the century. The majority of effects have been reported among highly
      exposed groups including occupational populations, such as chemical production
      workers, pesticide applicators, and individuals who handled or were exposed to
      materials treated with 2,3,7,8-TCDD-contaminated pesticides, and among residents
      of communities contaminated with tainted waste oil (Missouri, USA) and industrial
      effluent (Seveso, Italy). For only six exposed populations were biological
      measurements of 2,3,7,8-TCDD-contaminated collected and used to examine the
      relationship between non-cancer health effects and exposure. Of the many non
      cancer health effects thought to be associated with 2,3,7,8-TCDD exposure, only
      chloracne, elevations in GGT and triglyceride levels, and alterations in FSH and
      LH were related to serum 2,3,7,8-TCDD levels. Mortality from cardiovascular
      diseases also appeared to be elevated among cohorts of exposed chemical workers
      and Seveso residents. Continued surveillance of the health of exposed populations
      will be useful in identifying the long-term effects of both high and low 2,3,7,8
      TCDD exposure.

PMID- 10912245
TI  - Studies of cancer in humans.
AB  - The epidemiological evidence from the most highly 2,3,7,8-TCDD-exposed cohorts
      studied produces the strongest evidence of increased risks for all cancer
      combined, along with less strong evidence of increased risks for cancer of
      particular sites such as non-Hodgkin lymphoma, soft-tissue sarcoma and lung
      cancer. The relative risk for all cancer combined in the most highly exposed and
      longer-latency sub-cohorts is 1.4. While this relative risk is not likely to be
      explained by confounding, this possibility cannot be excluded. It should be borne
      in mind that the general population is exposed to 2-3 orders of magnitude lower
      levels of TCDD than those experienced by the equivalent life-time dose in the
      industrial populations examined or the population of Seveso.

PMID- 10912246
TI  - Health risks to infants from exposure to PCBs, PCDDs and PCDFs.
AB  - Global contamination by a variety of anthropogenic persistent organic chemicals,
      such as dioxins and PCBs, has resulted in human exposure throughout all phases of
      development. Detectable concentrations of PCBs and dioxins have been found in
      amniotic fluid, placenta and foetal tissue samples while infants who are breast
      fed can obtain blood levels greater than those of their mother's. In two separate
      food poisoning episodes where infants were exposed in utero to elevated levels of
      heat-degraded PCBs (PCBs, PCQs, PCDFs), a variety of adverse mental and physical
      developmental abnormalities have been observed. In additional human cohorts where
      exposure could be considered as environmental or background, more subtle effects,
      including lower birth weights, alterations in thyroid hormones and lymphocyte
      subpopulations and detriments in neurological development, have been consistently
      seen. In most instances, negative associations were made between in utero
      exposure to contaminants compared with lactational. Although the observed
      neurodevelopmental deficits have been described as subtle, there could be unknown
      consequences related to future intellectual functionality. Current regulatory
      efforts should focus on identification and control of environment and food chain
      contamination as in utero exposure is a direct consequence of the accumulated
      maternal body burdens.

PMID- 10912247
TI  - Risk ranges for various endpoints following exposure to 2,3,7,8-TCDD.
AB  - Conducting a dose-response analysis for an environmental contaminant requires a
      careful evaluation of most of the available data focusing on both the magnitude
      of the effect and the possible ranges of dose-response shapes which fit the data.
      This paper calculates potency values (1% response exposures) for human and animal
      data on cancer, non-cancer and biological effect endpoints for TCDD and finds
      that a reasonable estimate for 1% excess cancer would be between 1 and 50
      pg/kg/day. The paper also evaluates the adequacy of linear and non-linear models
      for fitting these data and concludes that the assumption of a threshold dose
      response is not fully supported by these data.

PMID- 10912248
TI  - Human risk assessment and TEFs.
AB  - The concept of toxic equivalency factors (TEFs) has been developed to facilitate
      risk assessment and regulatory control of exposure to complex PCDD, PCDF and PCB
      mixtures. Recently the European Centre for Environment and Health of the World
      Health Organization (WHO-ECEH) and the International Programme on Chemical Safety
      (IPCS) jointly re-evaluated the TEFs of PCDDs, PCDFs and dioxin-like PCBs for
      mammals and derived consensus TEFs for birds and fish (Stockholm, 1997). From a
      mechanistic point of view it can be concluded that, although the quantitative
      response will vary depending on the congener involved, the occurrence of a common
      mechanism (binding to the Ah receptor) legitimates the use of the TEF concept
      across species. But there also is criticism regarding the TEF concept.
      Pharmacokinetic differences between species can significantly influence the TEF
      value, and uncertainties due to additive or non-additive interactions, to
      differences in species responsiveness and to differences in the shape of the dose
      response curve might hamper the derivation of consensus TEF values. In this
      context it should be noted, however, that using TCDD alone, as the only measure
      of exposure to dioxin-like PCDDs, PCDFs and PCBs, would severely underestimate
      the risk from exposure to these compounds. Therefore, it can be concluded that,
      for pragmatic reasons, the TEF concept remains the most feasible approach for
      risk assessment purposes, in spite of the uncertainties associated with its use.

PMID- 10912249
TI  - Current risk assessment approaches in different countries.
AB  - Polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls
      (PCBs) exist as complex mixtures in environmental and biological samples. There
      is sufficient evidence that the toxic congeners share a common mode of action,
      involving binding to the Ah-receptor. Toxic equivalency factors (TEFs) and
      chemical residue data are used to calculate toxic equivalent (TEQ) concentrations
      in environmental samples, foods, animal and human tissues. Two different
      approaches have been used in the risk assessments of PCDDs, PCDFs and dioxin-like
      PCBs. WHO and most countries outside the USA have derived Tolerable Daily (or
      weekly) Intakes (TDI) in the order of 1-10 pg per kg of body weight for TCDD or
      TEQs based on data from rodent carcinogenicity studies. These countries have
      assumed the existence of a threshold dose for the carcinogenicity of dioxins,
      while US EPA and USFDA have used probabilistic estimates of cancer potency,
      treating cancer as a non-threshold effect and using a descriptor that addresses
      upper bound risk, the Risk Specific Dose (RsD). In the USA and other countries
      there is a growing concern over the non-cancer effects of dioxin-like compounds.
      In general, the various risk assessments have identified groups of the population
      that are at particular high risks and all have stressed the urgent need to reduce
      the sources of the environmental contamination with these compounds to the lowest
      possible.

PMID- 10912250
TI  - Prevalence and natural history of primary speech and language delay: findings
      from a systematic review of the literature.
AB  - The prevalence and the natural history of primary speech and language delays were
      two of four domains covered in a systematic review of the literature related to
      screening for speech and language delay carried out for the NHS in the UK. The
      structure and process of the full literature review is introduced and criteria
      for inclusion in the two domains are specified. The resulting data set gave 16
      prevalence estimates generated from 21 publications and 12 natural history
      studies generated from 18 publications. Results are summarized for six
      subdivisions of primary speech and language delays: (1) speech and/or language,
      (2) language only, (3) speech only, (4) expression with comprehension, (5)
      expression only and (6) comprehension only. Combination of the data suggests that
      both concurrent and predictive case definition can be problematic. Prediction
      improves if language is taken independently of speech and if expressive and
      receptive language are taken together. The results are discussed in terms of the
      need to develop a model of prevalence based on risk of subsequent difficulties.

PMID- 10912251
TI  - A comparison of three therapy methods for children with different types of
      developmental phonological disorder.
AB  - Treatment case studies of three children whose speech was characterized by non
      developmental errors are described. Three therapy methods were trialed with each
      child: phonological contrast; core vocabulary and PROMPT. The accuracy and
      intelligibility of the children's connected speech improved throughout the course
      of the programme. Intervention that focused on teaching a rule about the
      contrastive use of phonemes was most successful for a child who consistently made
      non-developmental errors. Children making inconsistent errors received most
      benefit from the core vocabulary approach that markedly enhanced consistency of
      production. However, once consistency was established, one child benefited from
      phonological contrast therapy. While the results of the study should be
      interpreted with caution due to the small sample size and the cumulative effects
      of intervention, the findings suggest that different parts of a child's
      phonological and phonetic system may respond to various types of treatment
      approaches that target different aspects of speech production. The implication
      drawn is that just as no single treatment approach is appropriate for all
      children with disordered phonology, management of some children may involve
      selecting and sequencing a range of different approaches.

PMID- 10912252
TI  - Correlates of social development in children with communication disorders: the
      concurrent predictive value of verbal short-term memory span.
AB  - Linguistic and cognitive correlates of social skill were examined in a clinically
      selected sample of children with communication disorders. Thirty-two children
      aged between 5 and 10 years were assessed using a questionnaire-based sociability
      scale. Specially designed measures of verbal and visuo-spatial short-term memory
      span were administered, as well as standardized tests of grammatical and lexical
      comprehension. Multiple regression analyses revealed strong prediction of social
      skill from STM measures but not from comprehension scores. The prediction was
      based on a striking negative correlation between serial word span and
      sociability. This word-span measure could offer a useful tool in the assessment
      of children with communication disorders. However, attention is drawn to the
      substantial number of children in the sample whose patterns of cognitive,
      linguistic and social skill are not clearly differentiated. It is suggested that
      assessment should aim to specify as clearly as possible individual patterns of
      strength and weakness and avoid unwarranted categorization.

PMID- 10912253
TI  - Language development following brain injury in early childhood: a longitudinal
      case study.
AB  - The present longitudinal case study was designed to investigate the possibility
      that a traumatic brain injury (TBI) occurring during the second year of life,
      while significant lexical and grammatical competencies are emerging, could have
      an impact on subsequent language development. Thus, the language development of a
      very young girl (BL) who suffered a TBI at the age of 17 months was monitored for
      6 months following the injury. Different procedures were used to measure her
      lexical and grammatical development: monthly parental checklists, free-play
      sessions and word-learning tasks. BL's results were compared with two control
      groups (n = 5 and 9) matched for age and gender. Overall, the results are
      consistent with the classical view of acquired language disorders in children:
      despite an initial decrease in the use of her premorbid vocabulary, BL showed no
      durable significant impairment on any measure of lexical or grammatical
      development.

PMID- 10912254
TI  - Language repair via metalinguistic means.
AB  - Children with specific language impairment (SLI) have been shown to be deficient
      in the use of complex sentences. In an attempt to remediate this area of
      weakness, two groups of such children (mean ages 9;4 and 10;6) received about 55
      half-hour sessions of metalinguistic training spread over 12 months. Results
      showed that the use of complex sentences increased to at least normal levels in
      the experimental groups, and were significantly improved, at both the written and
      oral levels, as compared with SLI control groups, which evidenced little change
      over the same period. Further analysis of the data revealed the striking finding
      that those children who had the poorest complex sentence usage tended to benefit
      the most from metalinguistic training. These results are interpreted as support
      for the hypothesis that metalinguistic training helps to overcome the presumed
      neurological deficit of the language disordered child by making linguistic rules
      conscious, and thereby providing a 'metalinguistic bridge' via which information
      can bypass the damaged area.

PMID- 10912255
TI  - Adult spoken discourse: the influences of age and education.
AB  - Spoken discourse is regarded as an important component of communication
      assessment, but data on the discourse characteristics of the adult population,
      and in particular those who fall into the fastest growing section of the
      population (those aged over 75), are scant. Therefore, detection of deficit is
      commonly dependent on the assessor's opinion as to what constitutes normal
      performance. To determine the effects of age, education and gender on spoken
      discourse, the conversational interaction and picture description skills of 189
      neurologically normal adults were examined. Conversation was appraised with
      reference to five parameters (initiation, topic maintenance, verbosity, turn
      taking, reference). Picture description was assessed for relevant content,
      length, efficiency and the inclusion of extraneous information. Level of
      education did not affect conversational interaction but in picture description
      those not educated beyond minimal school leaving produced shorter and less
      complete descriptions. Picture description content and length were not affected
      by advancing age but the older elderly (aged 75+) conveyed information with
      reduced efficiency. Conversational interaction style altered with advancing age,
      with some suggestion of change in the young elderly (age 60-74), but highly
      significant differences in respect of the old elderly. Gender had no effect on
      the parameters of conversation and no significant picture description differences
      were present in males and females though there were trends towards longer and
      higher content descriptions in females. The results have important diagnostic
      implications for those concerned with establishing whether pathology such as
      stroke has affected communication. On a wider scale, awareness of the effects of
      advancing age and limited education may facilitate successful communication for
      all who communicate with the public in a professional capacity.

PMID- 10912256
TI  - Reliability of speech and language therapists using therapy outcome measures.
AB  - The Therapy Outcome Measure (TOM) aims to provide Speech and Language Therapists
      (SLT) with a practical tool to measure outcomes of care by providing a quick and
      simple measure which can be used over time with patients and clients in a routine
      clinical setting. The TOM allows therapists to reflect their clinical judgement
      on the dimensions of impairment, disability/activity, handicap/participation and
      well-being on an 11-point ordinal scale. The purpose of this paper is to examine
      the reliability and the influences on reliability of SLT using this measure.
      Three studies are presented and give information on 73 SLT using the measure with
      different client groups. Study one assesses the degree of reliability of six SLT
      using the TOM following training and practice. Reliability was studied on three
      occasions and the results demonstrate the influence of training and practice.
      Study two included 56 SLT to examine reliability over a broader range of client
      groups and to investigate the effect of the SLT specializing on rating patients
      from within or -out that specialism. Eleven therapists were included in the
      study, which examined the influence of a specific training approach. The
      participating SLT achieved a substantial-moderate level of reliability; this was
      established in all domains. The degree of reliability achieved on the TOM was
      affected by some, but not extensive, training and experience.

PMID- 10912257
TI  - A multinational comparison of aphasia management practices.
AB  - The effect of restructuring of healthcare on the quality, quantity, and nature of
      aphasia management is largely unknown. The current study is the first to examine
      access, diagnostic, treatment, and discharge patterns of patients with aphasia in
      Australia, Canada, the UK, the US private sector (US-Private), and the US
      Veterans Health Administration in the Department of Veterans Affairs (US-VA). The
      authors developed a 37-item survey to be completed by clinicians working with
      aphasic patients. The survey focused on eight areas: access to care, evaluation
      procedures, group treatment, number and duration of treatment sessions,
      limitations of the number of sessions, termination of treatment, follow-up
      practices, and resumption of treatment. 394 surveys were distributed and 175 were
      returned completed (44% return rate). Respondents represented a range of ages,
      work experiences, and work settings. There was considerable consistency among
      respondents from our five healthcare systems. Results suggest that patients may
      be routinely denied treatment in direct contradiction to the research literature.
      Just as we carefully monitor the progress of patients receiving our treatment, we
      are obliged to monitor the effects of managed care on our patients, fellow
      clinicians, and our profession.

PMID- 10912259
TI  - Training in otorhinolaryngology: a European perspective.

PMID- 10912258
TI  - The future of head and neck surgery.

PMID- 10912260
TI  - Effect of anaesthetic agents on tympanometry and middle-ear effusions.
AB  - Following informed parental consent 93 children underwent bilateral grommet
      insertion. Tympanometry was performed pre-operatively, and immediately prior to
      myringotomy. A standardized anaesthetic was used. At myringotomy the presence or
      absence of fluid was recorded, as well as the time since induction of the general
      anaesthetic. A pre-operative type B tympanogram predicted a middle-ear effusion
      at myringotomy in 92 per cent of patients. A pre-operative type C2 tympanogram
      predicted a middle-ear effusion at myringotomy in 39 per cent of patients. Sixty
      tympanograms (30 per cent) changed following a general anaesthetic. Fourteen type
      B tympanograms changed to type A and eight of these had effusions. The duration
      of the general anaesthetic did not influence the probability of a middle-ear
      effusion being present at myringotomy. A pre-operative type B tympanogram is a
      good predictor of middle-ear fluid. The duration of the general anaesthetic is
      not significant in predicting the presence of a middle-ear effusion.

PMID- 10912261
TI  - The arcuate eminence is not a protrusion of the superior semi-circular canal but
      a trace of sulcus on the temporal lobe.
AB  - Thirteen cadavers (26 temporal bones) were examined to show the arcuate eminence,
      especially its correspondence to the superior semicircular canal and inferior
      surface of the temporal lobe. Arc-like eminences on the petrous bone were
      observed in 92 per cent of specimens, however, they did not exactly correspond to
      the superior semi-circular canal. Some eminences corresponded to sulci of the
      temporal lobe of which most were traces of the occipitotemporal sulcus. On the
      other hand, a dull, smooth and even domed eminence existed in nine temporal bones
      independently of the arc-like eminence. Those eminences corresponded to each
      superior semi-circular canal in only three out of nine specimens. The arcuate
      eminence was listed as an important landmark in the middle cranial fossa
      approach. However, in order to drill out the internal auditory canal safety,
      surgeons should rely on other landmarks or apply other methods from our data.

PMID- 10912262
TI  - Risk management of asymmetrical hearing impairment in an armed forces population.
AB  - The prevalence of asymmetrical hearing impairment in the entire service
      population (1490 individuals) of a Royal Air Force flying station was estimated
      from routine audiometric testing recorded in individuals' medical records.
      Criteria for magnetic resonance imaging (MRI) scanning to exclude the possibility
      of vestibular schwannoma were determined in accordance with the risk management
      principle that the cost of the screening should not exceed the value of the
      likely benefit. MRI scanning should be carried out in the presence of an
      asymmetrical sensorineural hearing impairment of (a) 15 dB or more at two
      adjacent frequencies, or (b) 15 dB or more averaged over 0.5, 1, 2, 3, 4, 6 and 8
      kHz.

PMID- 10912263
TI  - Maxillary sinus polyps secondary to dental extraction.
AB  - Polyps of the maxillary sinus were obtained from six patients who had reported
      upper tooth extraction with oroantral perforation prior to the development of
      symptoms, from 11 patients with chronic sinusitis, and from 12 patients with
      allergy. Histopathological features, scanning electron microscopy of the polyp
      epithelium and clinical data were compared in those groups of patients. The post
      traumatic polyps differed from those of other aetiologies by showing the presence
      of granulomas, less numerous inflammatory cells with very few eosinophils, nearly
      normal surface epithelium (smaller surface area occupied by nonciliated
      epithelium, absence of epithelial squamous cells, normal frequence of goblet
      cells), rapid appearance of symptoms, and shorter duration of the disease. It
      seems that the specific characteristics of the injury-induced polyps results from
      a different mechanism of their formation, involving primarily abnormal mucosal
      repair and to a lesser extent an inflammatory process.

PMID- 10912264
TI  - Clinico-pathological correlation between allergic rhinitis and bronchial asthma.
AB  - A prospective study was carried out on 52 patients with allergic rhinitis, during
      March 1993-January 1995. This was to analyse the occurrence of bronchial asthma
      among them and to correlate the symptoms, signs and pathological findings of
      allergic rhinitis with that of bronchial asthma in those patients with both the
      disorders. The therapeutic benefits with regard to the symptoms of bronchial
      asthma in these patients were assessed after treatment of their nasal allergy for
      a period of at least four months. A definite aetio-clinico-pathological
      correlation could be established between allergic rhinitis and bronchial asthma
      and it could be concluded from the study that prompt attention to nasal symptoms
      in cases with co-existent bronchial asthma helps to a large extent in curbing the
      symptoms of the latter.

PMID- 10912265
TI  - Tubular expanded polytetrafluoroethylene implants in glottal and neoglottal
      insufficiency: implantation technique in an animal model.
AB  - The problem of the therapy of glottal and neoglottal insufficiency is still
      unsolved. The surgical techniques and the materials employed up until now are not
      completely free from possible partial or total failures, early or late
      complications, or the need of a second operation. The objective of the study is
      to introduce a new thyroplasty technique of inserting tubular expanded
      polytetrafluoroethylene (e-PTFE) into the larynx of an animal model, with the
      purpose of using it next in human laryngeal tissue augmentation. Seven 30 kg pigs
      had tubular e-PTFE implanted under endoscopic control into a vocal fold or
      laryngeal vestibule. The implants were secured by suture to the thyroid
      cartilage. Short-term results demonstrate the ease and effectiveness of this mini
      invasive implant surgical technique. Long-term follow-up is underway in
      anticipation of applying this technique to human laryngeal tissue augmentation.

PMID- 10912266
TI  - Novel method for the application of anti-mist solution to surgical endoscopes.
AB  - Endoscopes require repeated cleaning and application of anti-mist solution during
      surgery. A novel, simple and inexpensive method of application of the anti-mist
      solution is described.

PMID- 10912267
TI  - Non-pseudomonal malignant otitis externa and jugular foramen syndrome secondary
      to cyclosporin-induced hypertrichosis in a diabetic renal transplant patient.
AB  - We present the case of a 58-year-old diabetic renal transplant patient who
      developed a left jugular foramen syndrome, secondary to an ipsilateral
      staphylococcal malignant (necrotizing) otitis externa. This followed a protracted
      episode of uncomplicated otitis externa with no evidence of bone involvement on
      computed tomography (CT) scanning. Cyclosporin-induced hypertrichosis (excess
      hair growth) in his external auditory canal contributed greatly to the initial
      difficulty in managing his otitis externa. Following an initial successful
      treatment with prolonged intravenous antibiotics the patient relapsed with a
      secondary infection in the same anatomical site due to Candida parapsilosis.
      Despite further intensive treatment including antimicrobials, a subtotal
      petrosectomy and hyperbaric oxygen therapy he eventually succumbed to his
      disease.

PMID- 10912268
TI  - Paraganglioma of the external auditory canal: an unusual case.
AB  - Primary paraganglioma of the external auditory canal is a rare otological
      finding. To date, only three cases have been reported in the world-wide
      literature. Such a tumour is now described in a 42-year-old female. The clinical
      and histopathological features of the case are discussed. The role of
      immunocytochemistry in defining diagnosis, from a large list of differentials, is
      illustrated. We present the first magnetic resonance images of this rare tumour
      and highlight the benefit of intra-operative frozen section in limiting surgery
      to canal excision.

PMID- 10912269
TI  - Abscess formation in the temporomandibular joint as a complication of otitis
      media.
AB  - A case of an eight-month-old girl with an abscess in the temporomandibular joint
      as a complication of acute otitis media is described. The complications of acute
      otitis media in general and the probable explanation for the development of this
      complication are discussed.

PMID- 10912270
TI  - When a mastoid swelling is not mastoiditis.
AB  - A case is reported of swelling over the mastoid process due to subgaleal abscess
      possibly secondary to trivial cutaneous trauma. The diagnosis was difficult as
      subgaleal abscess is an extremely rare condition especially after the advent of
      the antibiotic era. The route of entry of the infection to the subgaleal space
      was unclear as there was no skin puncture. The absence of substantial trauma
      excluded subgaleal haematoma as a precondition. We would like to discuss the
      possible aetiologies and the management of this rare case in the light of the
      limited information available in the world literature.

PMID- 10912271
TI  - Plasmacytoma of the mastoid bone: solitary and systemic.
AB  - Plasma cell tumours of the mastoid are rare malignancies of haematological
      origin. Two patients are described with a plasma cell tumour in the mastoid bone.
      In one patient it concerned a solitary plasmacytoma of the bone and in the other
      a focus in the mastoid of a recently diagnosed multiple myeloma. Symptoms in
      these patients were non-specific. Computed tomography (CT) and magnetic resonance
      image (MRI) scanning showed a non-specific space-occupying lesion in the mastoid.
      The diagnosis was made on immunohistological examination, that showed diffuse
      sheets of monoclonal plasma cells in a clear matrix. When a plasmacytoma lesion
      is found multiple myeloma should always be excluded. Treatment in case of
      solitary plasmacytoma of the mastoid bone consists of radiotherapy. In case of
      localization in the mastoid of multiple myeloma the treatment consists of
      palliative chemotherapy.

PMID- 10912272
TI  - Angiosarcoma of the maxillary sinus.
AB  - Angiosarcomas are rapidly growing malignant neoplasms arising from the vascular
      endothelial cells. Most common sites are the extremities and the retroperitoneal
      space, with only four per cent of angiosarcomas arising in the head and neck
      area, whilst the paranasal sinuses are one of the rarest locations. We report the
      case of a maxillary sinus angiosarcoma in a 72-year-old male patient. The first
      biopsy was inconclusive, whereas the second revealed an angiosarcoma. Medial
      maxillectomy was performed with subsequent external irradiation.

PMID- 10912273
TI  - Unusual presentations of isolated sphenoid fungal sinusitis.
AB  - Isolated sphenoid fungal sinusitis is a rare and often difficult to diagnose
      condition as the presenting symptoms are often vague and non-specific. In this
      series each case has a different clinical presentation with a different causative
      fungus. Although isolated fungal sphenoid sinusitis is usually seen in
      immunocompromised individuals, two of the three cases presented were
      immunocompetent. The fungi were Pseudallescheria boydii, Aspergillus fumigatus
      and Schizophyllum commune. In order to illustrate the great diversity of clinical
      signs, each case is individually presented. The characteristic radiological signs
      and the clinical management of each case are also presented. The danger signs of
      associated pathology are discussed with particular reference to an associated
      squamous carcinoma in one case. Surgical options and chemotherapy are discussed.
      Isolated sphenoid fungal sinusitis is a rare condition that if undiagnosed may
      result in considerable morbidity and even mortality of patients.

PMID- 10912274
TI  - Neck mass caused by an intraluminal jugular paraganglioma.
AB  - Paragangliomas can develop in a number of head and neck sites, the most common
      being the carotid body paragangliomas and glomus jugulare tumours. This is a case
      of a paraganglioma confined entirely within the lumen of the jugular vein.

PMID- 10912275
TI  - Narrow internal auditory canal syndrome: parasaggital reconstruction.
AB  - Narrow internal auditory canal (IAC) syndrome is a malformation of the temporal
      bone, that is defined as an IAC diameter of only 1-2 mm on high-resolution
      computed tomographic scans (HRCT). This syndrome is known to be caused by the
      absence (aplasia or hypoplasia) of the vestibulocochlear nerve. We present a case
      of unilateral narrow IAC syndrome which was diagnosed by HRCT. The aplasia of the
      vestibulocochlear nerve was confirmed using parasigittal reconstruction magnetic
      resonance image (MRI). The IAC was composed of two separate canals, one of which
      contained a facial nerve and the other was empty with aplasia of the
      vestibulocochlear nerve.

PMID- 10912276
TI  - Imaging for endoscopic sinus surgery in adults.
AB  - Computerized tomography (CT) offers the gold standard in terms of imaging the
      extent of disease and the fine detailed anatomy, both pre-requisites to the safe
      practice of endoscopic sinus surgery. Neither plain X-rays nor magnetic resonance
      imaging (MRI) offer optimal information in this respect. A variety of protocols
      minimizing radiation dose to the lens whilst providing high quality images are
      presented together with a menu of anatomical features that require careful
      evaluation pre-operatively.

PMID- 10912277
TI  - Laryngeal leiomyosarcoma.
AB  - We report one case of leiomyosarcoma (LMS) of the larynx occurring in a patient
      with a history of immunosuppressive therapy, and offer a critical review of the
      literature. Epstein-Barr virus (EBV) genome was not identified in the neoplastic
      cells. The patient was treated with endoscopic resection and post-operative
      radiotherapy. Lung metastasis and thyroid infiltration became evident 14 months
      following treatment despite the absence of laryngeal recurrence. Progressive
      decline occurred and the patient died 15 months after diagnosis.

PMID- 10912278
TI  - A unique parotid adenocarcinoma.
AB  - A large number of different types of benign and malignant tumours of the salivary
      glands are recognized, and rare and unusual variants arise from time to time that
      can be difficult to interpret. We report an apparently unique parotid neoplasm
      that does not fit any of the currently recognized diagnostic groups and can best
      be termed lymphadenocarcinoma. Clinical and pathological features are described,
      and its possible relationship to recognized tumour types is examined.

PMID- 10912279
TI  - Controlling tuberculosis--is it really feasible?

PMID- 10912280
TI  - Expression of transforming growth factor-beta but not tumor necrosis factor
      alpha, interferon-gamma, and interleukin-4 in granulomatous lung lesions in
      tuberculosis.
AB  - The expression of transforming growth factor (TGF-beta 1), tumor necrosis factor
      alpha (TNF-alpha), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) were
      assessed in lung tissues from patients with tuberculosis. Vimentin, a
      constitutively expressed cellular protein, was present in 12 of 19 tissue
      sections indicating adequate preservation of tissue proteins in these cases.
      Immunohistochemical studies for cytokines were done in the vimentin positive
      sections only. TGF-beta 1 was localized to mononuclear phagocytes of tuberculous
      lung lesions in 4 of 12 tuberculosis patients. TNF-alpha, IFN-gamma, and IL-4
      were absent in sections from all tuberculosis patients. The failure to detect the
      latter cytokines may indicate that these molecules may not be expressed at the
      site of disease, or are not a feature of the late stages of tuberculous
      granulomas. TGF beta-1, although not universally expressed, may be involved in
      the development and/or consequences of tuberculous granuloma formation. These
      data substantiate further the role of TGF-beta 1 in the immunopathology of
      tuberculosis.

PMID- 10912281
TI  - Identification of possible loci of variable number of tandem repeats in
      Mycobacterium tuberculosis.
AB  - Three VNTR loci were previously cloned from Mycobacterium tuberculosis in our
      laboratory. The VNTR sequences were used as queries to search for similar
      sequences in the GenBank database by the BLAST program. Direct and tandem repeats
      were identified visually. The search revealed 45 more loci of direct and tandem
      repeats. Comparison of the sequences to the ones in the genome sequence database
      of the M. tuberculosis CDC1551 strain revealed 22 different loci. Combining these
      results with previously reported experimental work, at least 24 loci should be
      polymorphic enough to be detected by simple PCR. The repeats are present both
      inside coding sequences and in intergenic regions on the 5' or 3' ends of genes.
      M. tuberculosis contains several VNTR. Studies of their functions may be useful
      for understanding the differences of phenotypes between strains.

PMID- 10912282
TI  - Molecular fingerprinting of Mycobacterium tuberculosis strains isolated in
      Vietnam using IS6110 as probe.
AB  - SETTING: Northern and Southern areas of Vietnam. OBJECTIVE: To study the
      correlation between DNA fingerprinting of 168 Mycobacterium tuberculosis strains
      isolated from patients with a particular historical past (political separation of
      Vietnam for 20 years) and data about geographical origin, drug susceptibility,
      HIV infection and BCG vaccination status. METHODS: Comparison of restriction
      fragment length polymorphism (RFLP) patterns produced by Southern hybridization
      of Pvull-digested chromosomal DNA. RESULTS: The number of IS6110 copies for the
      168 strains ranges from 0 to 23. Strains originating from the North or the South
      differ strongly with respect to the number of copies of IS6110. Indeed, the
      strains originating from the north have predominantly from 3 to 14 IS6110 copies
      while the southern strains have predominantly from 15 to 23 IS6110 copies.
      Furthermore, strains isolated in the North are dispersed into 6 groups whereas
      80% of the strains isolated in the South form a single group. Moreover, the
      prevalence of drug resistance is higher in strains isolated in the South than in
      the North. No noticeable correlation is observed between RFLP patterns, drug
      susceptibility, or HIV infection. CONCLUSION: The IS6110 fingerprints of 168 M.
      tuberculosis strains isolated in Vietnam showed a high range of polymorphism.
      Only a few strains have been found with no IS6110 (1.8%). The differences between
      the strains from the North and South, having more than six IS6110, suggests that
      they derived from ancestral strains that would be distinguishable by the number
      of IS6110 and their transposition sites throughout the genome. The genomic
      structure of the population of strains from South Vietnam resembles that of the
      Beijing strain population. This could account for a similar evolution of M.
      tuberculosis due to a selection by BCG-induced immunity in the two populations.

PMID- 10912283
TI  - Heat disinfection of clinical waste: microbiological assessment and monitoring of
      effectiveness.
AB  - Simple, rapid and reproducible protocols are described for the microbiological
      assessment of clinical waste treatment processes, using Bacillus subtilis spore
      tests and end-product sampling. The use of these protocols to commission a new
      heat disinfection system (HDS), based on a hot oil-filled auger, and to monitor
      it over the first 21 months of operation is described. It is suggested that these
      protocols are suitable for assessment of other non-burn heat-treatment
      technologies.

PMID- 10912284
TI  - Isolation of methicillin-resistant Staphylococcus aureus from non-sterile sites:
      evaluation of a new selective medium.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) are relatively common
      nosocomial isolates, causing problems for health-care professionals worldwide.
      Therefore, early detection of the organisms by the laboratory is essential. A new
      selective medium for MRSA is described, comprising a DNA-containing base and a
      combination of stains that permit direct visualisation of DNase activity around
      colonies. The medium is made partially selective by adding a number of
      antibiotics (aztreonam, polymyxin B, nystatin and oxacillin). When compared to
      other media used for the isolation of MRSA, it was found that the new medium
      allowed earlier detection of colonies and provided a good direct method of
      identification, reducing the need for time-consuming replating of colonies, and,
      therefore, the turnaround time for specimens entering the laboratory for MRSA
      screening.

PMID- 10912285
TI  - Bacteraemia among patients attending a cancer hospital in Lahore, Pakistan.
AB  - Bacteraemia can be life-threatening, particularly in the neutropenic cancer
      patient, and any episode of pyrexia is treated empirically with antibiotics, and
      a blood culture taken. Over an 18-month period, 3025 (934 patients) blood culture
      sets were received by the microbiology department of the Shaukat Khanum Memorial
      Cancer Hospital and Research Centre, Lahore, Pakistan. The blood culture sets
      used a blood/tryptone soya broth (1:5 ratio) mixture and were manually
      subcultured onto appropriate media following incubation at 37 degrees C. Of
      these, 406 (13.4%) were positive for bacteria or yeasts, the most common
      organisms being coagulase-negative staphylococci (16%), Escherichia coli (15.1%),
      other Enterobacteriaceae (11.8%), Staphylococcus aureus (9.1%) and Pseudomonas
      aeruginosa (8.6%). In addition, a number of unusual organisms were isolated which
      could have been peculiar to this institution or to patients with neoplastic
      disease. Sensitivity patterns for the major groups of organisms were compared
      with the previous year's figures (where available), to identify any change.

PMID- 10912286
TI  - Detection of Chlamydia trachomatis antigen in spontaneous abortions. Is this
      organism a primary or secondary indicator of risk?
AB  - In order to investigate whether or not Chlamydia trachomatis infection is a risk
      factor for pregnancy loss, 77 spontaneous abortion patients (6-24 weeks
      gestation), admitted to gynaecology emergency of Safdarjang Hospital, New Delhi,
      India. Twenty-five pregnant women (6-16 weeks gestation) attending the same
      hospital for induced abortion, were included in the study. C. trachomatis antigen
      was detected in endometrial curretage tissue by enzyme immunoassay (EIA). The
      detection rate was 15.6% (12/77) among spontaneous abortion patients and 4%
      (1/25) among women undergoing induced abortion. There was no statistically
      significant association between the mean age/mean gestational age of those
      experiencing spontaneous abortion, with and without C. trachomatis infection
      (26.9 years versus 25.06 years and 11.1 weeks versus 9.6 weeks, respectively).
      High prevalence of C. trachomatis was found in multigravidae and parous
      spontaneous abortion patients, compared with that in primigravidae and
      nulliparous Chlamydia-negative spontaneous aborters (75.0% versus 25.0%; 66.7%
      versus 33.3%, respectively). The prevalence of chlamydial antigen in patients
      with no prior history of spontaneous abortion was 16.1% (10/62) compared with
      18.1% (2/11) in women with one prior abortion. Further study is required to
      determine whether C. trachomatis infection is a primary or secondary indicator of
      risk.

PMID- 10912287
TI  - Effect of polysaccharide krestin on glutathione peroxidase gene expression in
      mouse peritoneal macrophages.
AB  - Polysaccharide krestin (PSK) is a protein-bound polysaccharide extracted from the
      sporophore Coriolus versicolor. Previously, we found that PSK could reduce the
      oxidative injury that oxidised low-density lipoprotein (Ox-LDL) produced in
      monocytes/macrophages, and therefore have some pro-phylactic or therapeutic
      effect on atherosclerosis. Glutathione peroxidases, including selenium-dependent
      glutathione peroxidase (SeGPx) and non-selenium-dependent glutathione peroxidase
      (non-SeGPx, also called glutathione S-transferase [GST]), play an important role
      in the defence against oxidative injury. In order to find out if the effects of
      PSK were associated with antioxidant enzymes, we investigated its effect on
      glutathione peroxidase activity and messenger RNA (mRNA) expression in mouse
      peritoneal macrophages. Results showed that PSK enhanced SeGPx and non-SeGPx
      activity, and increased SeGPx and GST-P (pi class GST) mRNA in mouse peritoneal
      macrophages. In addition, the induction by PSK of the two glutathione peroxidases
      could be blocked by cycloheximide (30 micrograms/mL), but 5 micrograms/mL
      actinomycin D and 50 micrograms/mL acetovanilone (a superoxide inhibitor) had no
      effect. We conclude that PSK improved glutathione peroxidase activity through
      transcriptional induction of mRNA expression.

PMID- 10912288
TI  - Deoxyribonucleic acid restriction digest patterns in Campylobacter species: a
      comparison with Penner serotype.
AB  - Diversity, based on restriction fragment length polymorphism (RFLP) analysis, was
      studied in 48 strains of Campylobacter, comprising 27 chicken and 21 human
      strains of C. jejuni and C. coli, using genomic Southern hybridisation.
      Restriction digests of chromosomal DNA were prepared by treating with HaeIII and
      probed using a C. jejuni DNA probe. Nineteen distinct hybridisation patterns were
      identified, and differences in hybridisation pattern between members of the two
      species, and in individual strains of the same species, were seen. The method
      described proved more discriminatory than the Penner serotype, as strains from
      the same serotype were distinguished. The relative simplicity of the patterns
      obtained, together with the apparent diversity identified among individual
      strains and species, suggests that DNA fingerprinting using the C. jejuni DNA
      probe could be a useful identification method in epidemiological studies of
      Campylobacter infection in Nigeria.

PMID- 10912289
TI  - Monoclonal reagents for rhesus-D typing of Irish patients and donors: a review.
AB  - Polyclonal anti-D reagents have been largely replaced by monoclonal reagents;
      however, although generally very potent, they can exhibit some variation in
      activity, particularly in the detection of weak Rhesus (Rh) D-positive cells.
      Hence, although patients and donors previously typed as Rh-D-negative (Du
      positive) are now being typed as Rh-D-positive, it is likely that two monoclonal
      reagents selected for Rh-D typing may give anomalous results. This has led to
      confusion in testing patients and donors in Irish laboratories. To address this
      problem, 29 commercially available monoclonal and monoclonal/polyclonal anti-D
      reagents were evaluated for reactivity with partial D and efficiency of weak-D
      detection, using the manual tube technique. The anti-D reagents used in column
      technologies (Biovue and Diamed) also were evaluated. Testing was limited by the
      availability of partial-D cells. The reagents directly agglutinated the majority
      of partial-D cells, with the exception of DVI, which required the indirect
      antiglobulin test for detection. Totem (Diagast) and Z039 (Scottish National
      Blood Transfusion Service) both directly agglutinated DVI. The weak-D detection
      rate for a number of immunoglobulin M (IgM) reagents was improved by incubation
      of initially negative tests. Sedimentation techniques, recommended for a number
      of reagents, were unsuitable for weak-D or partial-D detection. There were
      indications that IgM/IgG reagents gave lower direct-agglutination weak-D
      detection rates than did IgM reagents, although Totem and Novaclone produced
      results matching those of the IgM reagents. Laboratories should be aware of the
      guidelines for Rh-D typing of patients and donors, and select anti-D reagents
      accordingly.

PMID- 10912290
TI  - Inhibition of selective media in the isolation of thermophilic Campylobacter spp.
      from foods.

PMID- 10912291
TI  - Undetectable serum glucose concentration in a patient with priapism.

PMID- 10912292
TI  - Urinary antigen diagnosis of meningococcal disease.

PMID- 10912293
TI  - Fusobacterial infections: an underestimated threat.
AB  - The involvement of fusobacteria in a wide range of human and animal infection has
      long been recognised. Slow-growing anaerobes, often in polymicrobial culture,
      they are not always identified but are present mainly in the oropharynx, from
      where they are bloodborne to other sites or aspirated into the lung.
      Fusobacterium nucleatum is commonly found in periodontal disease and produces
      tissue irritants such as butyric acid, proteases and cytokines. It has strong
      adhesive properties due to the presence of lectins, and these outer-membrane
      proteins mediate adhesion to epithelia and tooth surfaces, and coagglutination
      with other suspected pathogens. F. necrophorum may cause necrotising tonsillitis
      and septicaemia, leading to the spread of infection and the development of
      abscesses in the lung and brain--a form of Lemierre's syndrome. Calf diphtheria,
      foot rot and other infections in animals are well defined, with the pathogenic
      mechanisms involving leucotoxins, endotoxins and adhesins. A foul smell produced
      by butyric acid and other metabolic products is common to all fusobacterial
      infections. Identification using simple tests is within the scope of most
      laboratories.

PMID- 10912294
TI  - Graft-versus-host disease in allogeneic bone marrow transplantation: the role of
      monoclonal antibodies in prevention and treatment.
AB  - Reconstitution of an individual's haemopoietic stem cells by bone marrow
      transplantation (BMT) is the recommended treatment for a number of haematological
      conditions, both malignant and non-malignant. Despite evolution in BMT technology
      over the past forty years, graft-versus-host disease (GvHD) remains a major,
      potentially lethal complication. GvHD normally affects the skin, liver and
      gastrointestinal tract, resulting in a high rate of morbidity. The standard
      prophylaxis for GvHD is a combination of methotrexate and cyclosporin A, but this
      is only partially effective. Acute GvHD is difficult to treat and many patients
      are resistant to steroid therapy. Alternative methods of prevention and treatment
      are now being sought, and include monoclonal antibodies (MAbs) which target T
      cells and cytokines. T-cell depletion of donor marrow using rat MAbs reduces the
      incidence of GvHD but can increase the chances of leukaemic relapse. Mouse MAbs
      also have been used but some produce severe side-effects. The most successful
      MAbs are those linked to toxins, and these immunotoxins (IT) have proved very
      effective in reversing steroid-resistant acute GvHD. MAb therapies are becoming
      increasingly important in the treatment and prevention of GvHD, and could replace
      steroids as the main treatment option in some situations. It is predicted that,
      ultimately, peripheral blood stem-cell transplantation will replace the use of
      BMT; however, this alternative stem-cell source will not remove the GvHD risks
      associated with allogeneic stem-cell transplantation. Therefore, reducing the
      risks will remain a major challenge in the successful allogeneic transplantation
      of haemopoeitic stem cells for the foreseeable future.

PMID- 10912296
TI  - Hippurate hydrolysis and speciation of thermophilic Campylobacter spp.

PMID- 10912295
TI  - Mammalian hexokinases and their abnormal expression in cancer.
AB  - The phosphorylation of glucose, a crucial step in cellular metabolism, is
      catalysed by hexokinases (HK), of which there are four (HKI-IV) in mammalian
      tissues. The brain HK, (HK1), like HKII and HKIII, has a molecular weight of
      approximately 100 kDa. HKII is insulin-sensitive and found in adipose and muscle
      cells. HKIV, also known as glucokinase, has a molecular weight of 50 kDa and is
      specific to liver and pancreas. Most brain HK is bound to mitochondria via
      porins, enabling coordination between glucose consumption and oxidation. Tumour
      cells are known to be highly glycolytic, and correspondingly increased expression
      of glycolytic enzymes, including HK, have been detected in resected tumours from
      patients with lung, gastrointestinal and breast cancer. In the latter group,
      further increases in HK activity were associated with metastatic disease. Some
      studies have demonstrated increased HK activity in renal tumours, and also have
      reported changes in the isoenzymic expression of HK. Experimental studies of the
      initiation and progression of liver tumours have demonstrated a shift in
      expression from that of HKIV to HKI and HKII, with increased HK binding to
      mitochondria and a > 100-fold increase in HK activity. However, studies using
      xenografts derived from gliomas found decreased HK activity corresponding with
      loss of chromosome 10, the carrier of the HKI gene. Compared with normal tissues,
      a number of mechanisms are associated with changes in HK activity seen in tumours
      of the liver and other sites, and these include HK gene dosage, increased
      transcription, modulation of HK promoter activity by a broader range of
      effectors, and increased mitochondrial binding of HK. Increased HK activity,
      together with increased glucose transport by tumour cells, has been exploited in
      cancer imaging using the positron-labelled glucose analogue (18F)fluoro-2-deoxy-D
      glucose (FDG), which is transported into cells and then phosphorylated, but
      undergoes little further metabolism. Accumulated FDG then can be detected using
      positron emission tomography (PET).

PMID- 10912297
TI  - Fugitive discharges from waste disposal treatments.

PMID- 10912298
TI  - Arm oedema following breast cancer treatment.
AB  - Chronic swelling of the arm due to lymphoedema is a common complication of breast
      cancer treatment. As well as deformity, the condition can cause feelings of
      heaviness, tightness and aching in the arm. It can also lead to anxiety or
      depression, and difficulties with adjustment to the cancer and in family
      relationships. Here, we consider how arm oedema should be managed.

PMID- 10912299
TI  - The management of spasticity.
AB  - Spasticity is a frequent feature of neurological disease in adults and children.
      Commonly associated symptoms include impaired movement, painful muscle spasms,
      stiffness and disturbed sleep. Severe or long-standing spasticity may lead to
      contractures and joint ankylosis, which can severely restrict the patient's care
      and rehabilitation. Here, we review the management of patients with spasticity,
      concentrating on the role of drug treatment.

PMID- 10912300
TI  - [symbol: see text] Tiagabine: add-on treatment for partial seizures.
AB  - Up to 30% of patients with epilepsy have seizures resistant to available
      treatments. We consider here the place of [symbol: see text] tiagabine (Gabitril
      Sanofi-Synthelabo), which was recently introduced as an "add-on therapy for
      partial seizures with or without secondary generalisation where control is not
      achieved by optimal doses of at least one other anti-epileptic".

PMID- 10912301
TI  - The importance of diabetes as a cardiovascular risk factor.

PMID- 10912302
TI  - Renal protection: progression, regression, remission from nephropathy beyond
      blood pressure control.

PMID- 10912303
TI  - Correlations of left ventricular hypertrophy with cardiovascular mortality.

PMID- 10912304
TI  - Sub-optimal ACE-inhibitor prescribing and increased all-cause mortality risk. A
      critical evaluation of routine clinical care.

PMID- 10912306
TI  - The optimal management of brain metastases.

PMID- 10912305
TI  - Viagra and male erectile dysfunction: prescribing restrictions should be
      abolished.

PMID- 10912307
TI  - Chronic hepatitis C beta-interferon-induced severe hypertriglyceridaemia with
      apolipoprotein E phenotype E3/2.
AB  - The mechanisms of hypertriglyceridaemia and changes in plasma lipoprotein
      subfractions by beta-interferon treatment were studied in a hepatitis C patient
      with apo E phenotype E3/2. Plasma levels of triglyceride (TG) were increased by
      treatment with 6 x 10(6) beta-interferon and reached 8.06 mmol/l at 4 weeks of
      treatment. Low energy and low fat diet reduced them to half the maximal level.
      Plasma levels of LDL1 (1.019 < d < 1.045)-C, LDL2 (1.045 < d < 1.063)-C, HDL2-C
      and HDL3-C were 0.39, 0.31, 0.21 and 0.28 mmol/l, respectively, which are low,
      but the plasma levels of IDL, which is a remnant of TG-rich lipoproteins, was
      normal at 7 weeks of treatment. The distribution of plasma lipoprotein
      subfractions returned to normal after interferon treatment was discontinued. The
      mass and activity of lipoprotein lipase (LPL) were reduced to half the baseline
      level by interferon treatment. The activity of hepatic triglyceride lipase (HTGL)
      which transforms IDL to LDL was normal. The patient's apo E phenotype was E3/2;
      with that phenotype the removal of TG-rich lipoproteins and IDL through the
      receptors of the remnant and LDL is impaired. But the IDL plasma level was
      normal, probably because of normal HTGL activity and high LDL-receptor activity.
      Lymphocyte LDL-receptor activity was double that of the control. We conclude that
      interferon caused the low mass and activity of LPL which in turn caused the
      hypertriglyceridaemia. And no retention of the remnant of TG-rich lipoproteins in
      this patient with apo E3/2 and low levels of LDL subfractions was due to the
      active removal of them through LDL-receptors as well as the impaired production
      of them by suppression of LPL by interferon.

PMID- 10912308
TI  - Are women discriminated against for lipid lowering therapy? Results from a
      prospective cohort of women with coronary artery disease.
AB  - The objective of the study was to compare the lipid management of men and women
      with documented coronary artery disease in 587 patients (433 men and 154 women)
      undergoing coronary angiography between 1991 and 1995. A fasting total
      cholesterol (TC) was measured in all patients on the morning of angiography. A
      postal/telephone follow-up was carried out one year after angiography in a
      subpopulation of 278 patients (194 men and 84 women) who were not taking lipid
      lowering therapy (LLT) or whose TC was > 5.2 mmol/l at the time of angiography.
      At baseline, mean TC was 5.89 mmol/l (SE 0.06) in the men and 6.47 mmol/l (SE
      0.09) in the women (p = < 0.0001). Action or recommendation to institute LLT was
      taken in 141 (32.7%) men and 62 (40.3%) women (p = 0.09). In the follow-up
      population, comparing men with women, 74 (38.3%) vs 39 (46.4%) were taking LLT (p
      = 0.21); 56 (28.9%) vs 26 (31.0%) had not undergone repeat TC testing (p = 0.73);
      when performed, repeat TC was 5.75 (0.09) mmol/l vs 5.64 (0.16) mmol/l (p =
      0.53); mean decrease in TC between baseline and follow-up was 0.86 (0.10) mmol/l
      vs 1.01 (0.21) mmol/l (p = 0.51). There was no significant gender difference in
      lipid management either at the time of coronary angiography or subsequent follow
      up, although the level of lipid-lowering drug use remained inadequate in both
      sexes.

PMID- 10912309
TI  - Behavioural and clinical findings in couples where the man presents with erectile
      disorder: a retrospective study.
AB  - Relevant data were extracted from the case records of a consecutive series of 128
      men (median age 57 years) who presented with erectile disorder and whose partners
      (median age 54 years) attended on the first or second consultation. The case
      records included responses to questionnaires addressing issues relating to sexual
      behaviour, used routinely in the clinic. Of these partners, 123 agreed to be
      clinically examined, including pelvic examination. The duration of erectile
      disorder ranged from less than one year to 40 years. Only about 10% of couples
      had experienced sexual kissing and/or caressing in the four weeks before
      presentation. Almost half the couples had not experienced any sexual activity for
      about 2.5 years. While 83.7% of men considered intercourse to be important to
      themselves, only 20.2% of the women rated intercourse somewhat or very important.
      Clinical evidence of urogenital atrophy was present in 33.3% of women over the
      age of 46 years. Three women had a vaginismic response to examination in the
      clinic and one of these women reported long term vaginismus pre-dating the onset
      of her partner's erectile disorder. One case of malignant ovarian tumour was
      identified. The observations from this study demonstrate the need to involve the
      partner in the assessment process of men presenting with erectile disorder.

PMID- 10912310
TI  - Is paediatric day case tonsillectomy desirable? The parents' perspective.
AB  - Tonsillectomy is the most commonly performed otolaryngological procedure in most
      units. There is considerable financial pressure to perform paediatric
      tonsillectomy as a day case. Responding to concern that day case tonsillectomy
      might not be welcomed by parents or felt to be in the best interests of the
      patients, we carried out an audit of paediatric tonsillectomy, by means of a
      questionnaire for parents and nursing staff to complete while 32 consecutive
      patients underwent tonsillectomy as inpatients. Although eight parents (25%) felt
      that day surgery should be an option, none of those surveyed felt that on this
      occasion their child was well enough to be discharged home six hours
      postoperatively. Furthermore, no child in the audit fulfilled all the essential
      discharge criteria at six hours. In this area, at least, it appears parents do
      not uniformly welcome paediatric day case tonsillectomy.

PMID- 10912311
TI  - Management of breast pain.
AB  - Mastalgia is a common problem among premenopausal women, and those with severe
      and protracted symptoms merit treatment. A range of non-hormonal and hormonal
      agents is available for symptom control among mastalgia sufferers but many are
      ineffective. Tamoxifen is the most effective and least toxic agent available for
      the treatment of severe chronic breast pain. Dosage with tamoxifen must be
      tailored to individual patient requirement and symptom control balanced against
      troublesome side-effects.

PMID- 10912312
TI  - Alternatives to hysterectomy for the treatment of excessive uterine bleeding.
AB  - Abnormal uterine bleeding is a common gynaecological problem that traditionally
      has been treated with hysterectomy. However, there are many other conservative
      treatment modalities that should be considered before hysterectomy. Medical
      therapies are effective in most cases. Endometrial ablation may be an effective
      surgical alternative to hysterectomy. This article reviews and updates the
      diagnostic concepts and management options for the treatment of abnormal uterine
      bleeding. The authors present a review of the pertinent literature and describe
      their experience with the latest balloon device for endometrial ablation therapy.

PMID- 10912313
TI  - Stalking: evil, illness, or both?
AB  - This article considers the definition and impact of stalking behaviours, and
      describes recent examples, as well as the characteristics and behaviours of
      stalkers. Current legal frameworks and their application are reviewed, including
      recent changes in the law. Management and treatment issues as well as attention
      to minimising a violent outcome and general ethical matters are discussed.

PMID- 10912315
TI  - Update on vancomycin resistance.
AB  - Enterococci can be responsible for severe infections such as endocarditis,
      meningitis and septicaemia and are one of the most important causes of nosocomial
      infections. Resistance in enterococci concerns many classes of antibiotics
      including, since 1986, glycopeptides. These antibiotics act by blocking cell wall
      formation, and resistance is due to synthesis of modified peptidoglycan
      precursors. Resistance can be acquired or intrinsic and strains may be resistant
      to vancomycin and teicoplanin, or to vancomycin only. Five types of glycopeptide
      resistance and their biochemical mechanisms have been described. Furthermore,
      strains that are dependent on vancomycin for growth have been isolated from
      clinical samples. Data suggest that resistance could originate in glycopeptide
      producing organisms or in enterococcal species intrinsically resistant to these
      antibiotics.

PMID- 10912314
TI  - DMARDs in the treatment of rheumatoid arthritis: current agents and future
      developments.
AB  - The purpose of this paper is to review the benefits and limitations of current
      disease-modifying antirheumatic drugs (DMARDs) used for the treatment of
      rheumatoid arthritis (RA). Literature about DMARD use in RA, both as monotherapy
      and in combination therapy, is reviewed. The efficacy and safety of methotrexate,
      antimalarials, gold-containing compounds, sulphasalazine, D-penicillamine,
      azathioprine and cyclosporin, as well as several new antirheumatic agents are
      considered. Controlled short-term clinical studies demonstrate that DMARDs are
      superior to placebo. Early and continuous use of DMARDs is necessary to slow
      joint damage and improve long-term outcomes. Unfortunately, long-term treatment
      with these drugs is frequently limited by loss of response and/or onset of
      serious adverse events. The efficacy of combination DMARD therapy has also been
      tested, but with mixed success, and the goals of combination DMARD therapy have
      yet to be fully realised. New DMARDs that have recently been introduced offer
      promise for future RA management.

PMID- 10912316
TI  - Ramipril.
AB  - Ramipril is a long-acting, lipophylic angiotensin converting enzyme inhibitor,
      its principle action is to inhibit the conversion of angiotensin I to the active
      angiotensin II. Ramipril is indicated in the treatment of hypertension,
      congestive cardiac failure (including that following acute myocardial
      infarction), nephropathy (with and without diabetes mellitus) and now, following
      the findings of the HOPE study, in the prevention of cardiovascular events
      (including myocardial infarction) in high risk individuals. This article
      concentrates on reviewing the evidence supporting ramipril's use in these
      indications.

PMID- 10912317
TI  - When is an aortic valve prosthesis too small? The need for dobutamine stress
      echocardiography.
AB  - We describe a patient who had undergone aortic valve replacement with a small
      prosthesis 10 years previously and who presented with exertional breathlessness.
      The resting transaortic pressure gradient was only 30 mmHg but increased to 165
      mmHg on dobutamine stress. Conventional resting echocardiography may fail to
      demonstrate abnormal prosthetic aortic valve function; in the presence of
      symptoms, dobutamine stress echocardiography should be considered.

PMID- 10912318
TI  - Transient pathological Q waves in suspected acute myocardial infarction:
      'electrical stunning'.
AB  - In acute coronary syndromes the development of pathological Q waves is usually
      taken as evidence of established myocardial infarction (MI). We describe two
      patients with suspected acute MI who developed transient pathological Q waves.
      Cardiac enzymes were normal and cardiac catheterisation showed severe proximal
      coronary disease. Recognition of 'non-infarction' Q waves is important and may
      influence management of these patients.

PMID- 10912319
TI  - Training in sigmoidoscopy: the experience of trainees in elderly medicine in East
      Anglia.
AB  - To assess the standard of training in postgraduate sigmoidoscopy in East Anglia,
      a questionnaire was prepared and distributed to pre-registration house officers
      (JHOs), senior house officers (SHOs) and specialist registrars (SpRs) in eight
      hospitals. The results suggest that practical instruction in technique is
      inadequate, and that most trainees perform too few sigmoidoscopies to become
      competent at either examining or recognising lesions. Many JHOs have not
      performed sigmoidoscopies or even witnessed important lesions in their early
      training. The training improved little during the SHO grade, with few trainees
      feeling happy with their training. The SpRs felt they were competent, although
      their training was thought inadequate. The current training programme needs
      detailed reassessment and improvement.

PMID- 10912320
TI  - Pott's puffy tumour: a rare cause of forehead swelling in a child.
AB  - We report a case of Pott's puffy tumour in a 12-year-old. Owing to the late
      development of the frontal sinuses, frontal sinus infection in children is rare.
      When present it can lead to osteomyelitis associated with forehead swelling.
      Early diagnosis and active treatment prevent progression to life-threatening
      intracranial spread.

PMID- 10912322
TI  - Thyrotoxicosis in Down's and Turner's syndromes: the likelihood of Hashimoto's
      thyroiditis as the underlying aetiology.
AB  - Biochemical thyrotoxicosis in young women is almost invariably due to Graves'
      disease. Its occurrence in females with Turner's and Down's syndromes, both of
      which are seldom associated with Graves' hyperthyroidism but are frequently
      allied to Hashimoto's thyroiditis, should alert physicians to the possibility of
      the latter. The discharge thyroiditis of Hashimoto's disease can be recurrent and
      protracted. A brisk response to antithyroid therapy would favour a thyroiditis
      and, in this circumstance, radio-iodine uptake should be reduced. The absence of
      TSH receptor antibodies in such cases, while not wholly refuting the notion of
      active Graves' disease, lends support to the existence of Hashimoto's
      thyroiditis.

PMID- 10912321
TI  - An unusual cause of Cushing's syndrome: primary pigmented nodular adrenal
      dysplasia.
AB  - We report a case of Cushing's syndrome due to primary pigmented nodular adrenal
      dysplasia (PPNAD) and discuss the diagnostic process and management of this rare
      case. The diagnosis of PPNAD is discussed in the context of other causes of
      Cushing's syndrome. Eighty-five per cent of cases of Cushing's syndrome are due
      to a pituitary corticotrophic tumour (Cushing's disease). Rarer causes include
      cortisol secreting adrenal adenoma and ectopic ACTH secretion. In the routine
      investigation of Cushing's disease it is not unusual to find bilateral adrenal
      nodules on the CT scan. We present a case of Cushing's syndrome in which this
      radiographic finding was present and yet the biochemical diagnosis was one of
      ACTH independent disease. Histology revealed PPNAD.

PMID- 10912323
TI  - A case of Noonan syndrome with pulmonary and abdominal lymphangiectasia.
AB  - Noonan syndrome is characterised by a Turner-like phenotype and a normal
      karyotype. Although it is reported to be associated with abnormalities of the
      lymphatic system, involvement of the pulmonary lymphatics is rare. We present a
      case of Noonan syndrome where a whole body scintigraphy revealed lymphangiectasia
      of the lower extremities, abdomen and lungs.

PMID- 10912324
TI  - The development of a digital image database of clinical photographs.
AB  - At the end of December 1998, the traditional clinical slide library at the Media
      Resources Centre University Hospital of Wales and University of Wales College of
      Medicine was closed to new acquisitions. This paper describes how a digital image
      database (Image AXS) has been customized to provide a source of rapidly
      accessible and easily searchable images, suitable for teaching and reference
      purposes. The basic functions of the program are explained and areas such as data
      integrity, image capture, storage, archiving and the impact that this technology
      has had on departmental workflow are discussed.

PMID- 10912325
TI  - A model for the implementation of a hybrid digital clinical photographic service.
AB  - This paper considers the potential that digital capture has for patient
      photography in a large teaching hospital, as well as drawing attention to the
      flaws of the technology which, at the present time, make it an unrealistic option
      for general use. It suggests that a 'hybrid' system--of analogue capture, digital
      storage and digital output--remains in place until digital camera technology
      becomes cheaper, more stable and more comparable with current 35 mm film
      technology. It makes recommendations for the digital storage and output of these
      images, and argues that the 35 mm slide be gradually phased out of large teaching
      hospitals' lecture theatres in order to help pave the way for a total digital
      service.

PMID- 10912326
TI  - The changing role of the medical illustrator.
AB  - The annual meeting of the Australian Institute of Medical and Biological
      Illustration in Melbourne in November 1998 included keynote addresses from
      Richard Morton and Robin Williams. Both speakers looked at the future of the
      medical illustration profession, and in particular the impact of new technology.
      This matter was also addressed by Joe Nicholls in a presentation given at the
      Institute of Medical Illustrators' Annual Symposium in Warwick, UK, in September
      1998. This paper is a synthesis of the ideas presented by these three speakers
      and elaborates on common themes in their presentations.

PMID- 10912327
TI  - Medical illustration in the UK: its current and potential role in medical
      education.
AB  - This paper describes how medical illustration has evolved to become increasingly
      important in undergraduate medical education, postgraduate medical education and
      continuing medical education, as new technologies have become available and new
      teaching methods have developed based on the emerging technologies. It also
      examines how the role of the medical illustrator has changed. The descriptor
      'medical illustration' fails to reflect the changing face of the profession and
      it is suggested that a new title is required to convey better the evolving role
      of the profession.

PMID- 10912328
TI  - Knowledge and acceptance of telemedicine in surgery: a survey.
AB  - A questionnaire was sent to the chief surgeons at 141 Swiss hospitals to evaluate
      their knowledge and acceptance of telemedicine in surgery. The response rate was
      69%. Ninety-three per cent of all surgical departments used computer technology,
      85% regularly used the Web and 88% had an internal hospital network. ISDN lines
      were used in 58% of the participants' hospitals. While 35% of respondents had
      participated at least once in networking, only 8% regularly used telemedicine.
      The opinion was that access to therapeutic advice (87%) was a better use of
      telemedicine than was obtaining a primary diagnosis (24%), although the majority
      accepted the principle of making (91%) and receiving (94%) a remote diagnosis.
      The survey suggested that surgeons are interested in telemedicine and open to its
      development, although their experience and knowledge are limited. Therefore,
      telemedicine in surgery may be advanced by creating surgical networks for
      teleconsultation and tele-education.

PMID- 10912329
TI  - Teledermoscopy--results of a multicentre study on 43 pigmented skin lesions.
AB  - We performed a multicentre study to evaluate the agreement between the direct
      clinical diagnosis and the telediagnosis of 43 cutaneous pigmented lesions.
      Digital clinical and dermoscopic images of the 43 pigmented skin lesions (11
      melanomas, 23 melanocytic naevi, three basal cell carcinomas, three lentigines,
      two seborrhoeic keratoses and one angiokeratoma) were sent by email to 11
      colleagues (six dermatologists, two residents in dermatology, one oncologist, one
      specialist in internal medicine and one general practitioner) in 10 centres.
      These 11 colleagues had different degrees of experience in dermoscopy. With
      histopathology as the gold standard, an average of 85% of the telediagnoses were
      correct, with results varying from 77% to 95%, whereas face-to-face diagnosis by
      an expert dermatologist was correct in 91% of cases. The kappa value for all
      participants ranged from 0.35 to 0.87. The results confirm that teledermoscopy
      can be a reliable technique for the diagnosis of pigmented skin lesions but one
      that will depend on the expertise of the observer.

PMID- 10912330
TI  - Teledermatology--the requirements of dermatologists in private practice.
AB  - Eighty-four dermatologists in private practice in Bavaria were surveyed by postal
      questionnaire. Of the 45 who responded (a 54% response rate), 96% used a computer
      in their private practice. Fifty-seven per cent of respondents owned systems with
      Pentium processors, while 23% were still using 386 or 486 processors. Most of
      them used the Windows 95, UNIX or Apple operating system. Of the respondents who
      had a modem, 74% used ISDN. There were few modems connected to the ordinary
      telephone network. Of all respondents, 56% used email regularly. Several possible
      teledermatology applications were proposed in the survey (i.e. teleconsultation,
      on-line/off-line videoconferencing, email attachments). Fifty-six per cent of
      respondents said that they would perform teleconsultations with dermatology
      clinics, 40% preferred a teleconsultation via telephone and computer, and 42%
      sending files via email. The survey demonstrated that a high proportion of
      dermatologists in private practice would use a teledermatology service.

PMID- 10912331
TI  - Transportation savings and medical benefits of a teleneuroradiological network.
AB  - Since 1996, Turku University Central Hospital has offered teleradiology
      consultations regarding computerized tomography examinations of the brain to
      three regional hospitals in Finland, in which neurosurgical or neuroradiological
      specialist services are not available, in order to avoid unnecessary patient
      transportation. We performed a retrospective survey of the teleconsultations
      performed in 1998. Medical records and the relevant radiology images were
      obtained. During the study period, teleconsultations were carried out for a total
      of 83 patients, of whom 16 were transported to the university hospital (i.e. 81%
      of these patients had avoided unnecessary transportation). The total savings
      amounted to 42,100 ECU. Of the 16 transported patients, 12 were immediately
      operated on in the university hospital. It was judged that, because of the
      consultation service, the patients undergoing an operation had benefited from a
      more rapid and a more complete recovery. In 1998 the teleradiology consultation
      service was established as part of the routine work of the Medical Imaging Centre
      and a fee for its services was adopted.

PMID- 10912332
TI  - The consistency of neuropsychological assessments performed via telecommunication
      and face to face.
AB  - Previous studies have suggested that cognitive assessments of adult psychiatric
      patients can be carried out as reliably via teleconsultation as they can face to
      face. However, the designs of these studies have often been less than
      satisfactory. The present study used videoconferencing at 128 kbit/s for the
      cognitive assessment of individuals with a history of alcohol abuse. Twenty-seven
      participants were given a range of assessments with two equivalent forms. One of
      the forms was given via videoconferencing and the other face to face. All
      participants were assessed using both media and the order of presentation was
      balanced across participants. Aspects of participant satisfaction with
      teleconsultations were also assessed, on 10-point scales. The teleconsultations
      were significantly longer (mean 40.7 min, SD 6.4) than the face-to-face sessions
      (mean 33.0 min, SD 5.3). For most of the outcome measures, cognitive assessment
      via teleconsultation produced similar results to face-to-face assessment. Most
      participants expressed high overall satisfaction with the teleconsultation (mean
      rating 8.2). The average ratings for the sound quality (mean 7.6) and visual
      quality of the equipment (mean 7.9) were also high. The findings imply that it is
      not necessary for patients and neuropsychologists to be present at the same
      location for cognitive assessments to be carried out.

PMID- 10912333
TI  - Psychiatric inpatient care planning via telemedicine.
AB  - We assessed the costs of psychiatric inpatient care-planning consultations to
      remote areas using videoconferencing, instead of the conventional face-to-face
      consultations at a hospital. The data were collected from all wards at the
      department of psychiatry of Oulu University Hospital over 11 months. A total of
      14 videoconferences were conducted with two primary-care centres located 220 km
      and 160 km from Oulu. During the same period, 20 conventional consultations at
      the Oulu University Hospital were also assessed. A questionnaire was completed by
      a total of 124 patients, relatives and health-care personnel; the response rate
      was about 90%. Of the respondents, 90% were satisfied with the quality of
      communication afforded by videoconferencing. At a workload of 20 patients per
      year, the cost of the videoconferences was FM2510 per patient; the cost of the
      conventional alternative was FM4750 per patient. At 50 care consultations per
      year, a remote municipality would save about FM117,000.

PMID- 10912334
TI  - An evaluation of a network for professional development in child and adolescent
      mental health in rural and remote communities.
AB  - In 1998 a telemedicine network was established in South Australia and the
      Northern Territory to deliver educational material to professionals working in
      child and adolescent mental health in remote areas. The network involved a wide
      range of health professions, from psychiatrists to psychologists and social
      workers. The first 12 months of network activity were evaluated by quantitative
      and qualitative techniques. Four sources of data were used: an activity log,
      questionnaires, interviews and action research. A total of 36 telemedicine
      sessions were held, ranging in duration from 45 to 90 min (average 56 min) and
      involving a total of 45 different professionals, who participated an average of
      four times each (range 1-15). The most common types of session were case
      discussions (47%), followed by specialist seminars (36%) and administrative and
      introductory sessions (17%). The benefits of the network included: networking and
      peer support; improved efficiency and reduced travel costs; and improved
      efficiency of health services. The problems included: costs; lack of access to
      technical support; and the need for staff induction and training.

PMID- 10912335
TI  - Technical evaluation of a low-bandwidth, Internet-based system for
      teleconsultations.
AB  - A low-bandwidth telemedicine system was evaluated in eight community hospitals
      connected to a central hospital via the Internet. PCs were used with
      videoconferencing software and modem connections to the telephone network. The
      average data connection rates, still-image transfer times and live-video
      transmission rates were determined. The time to send 640 x 480, 320 x 240 and 160
      x 120 pixel, 24-bit still images ranged from 29 s to 411 s. The average file
      transfer times for a 10 s MPEG video-clip was 8.6 min. The average live video
      frame rate was 1 frame/s (at the best image quality), with an average latency of
      3 s. The results suggest that Internet-based videoconferencing is acceptable for
      certain telemedicine applications.

PMID- 10912336
TI  - Internet-based transfer of cardiac ultrasound images.
AB  - A drawback to large-scale multicentre studies is the time required for the
      centralized evaluation of diagnostic images. We evaluated the feasibility of
      digital transfer of echocardiographic images to a central laboratory for rapid
      and accurate interpretation. Ten patients undergoing trans-oesophageal
      echocardiographic scanning at three sites had representative single images and
      multiframe loops stored digitally. The images were analysed in the ordinary way.
      All images were then transferred via the Internet to a central laboratory and
      reanalysed by a different observer. The file sizes were 1.5-72 MByte and the
      transfer rates achieved were 0.6-4.8 Mbit/min. Quantitative measurements were
      similar between most on-site and central laboratory measurements (all P > 0.25),
      although measurements differed for left atrial width and pulmonary venous
      systolic velocities (both P < 0.05). Digital transfer of echocardiographic images
      and data to a central laboratory may be useful for multicentre trials.

PMID- 10912337
TI  - A feasibility study of realtime telemedicine in Croatia using Internet
      videoconferencing.
AB  - We explored the feasibility of realtime telemedicine in Croatia using Internet
      videoconferencing. A 33 kbit/s link was established between a team of specialists
      in the General Hospital 'Sveti Duh' in Zagreb and a general practitioner's clinic
      in Selca, on the island of Brac. During a two-week study, 16 patients (median age
      51 years) were studied. Twenty-one teleconsultations (seven initial and 14 follow
      up visits) were conducted, 13 with a specialist in internal medicine, six with a
      surgeon and two with a neurologist. In 18 cases (86%) telemedicine successfully
      replaced hands-on examination. The mean duration of the teleconsultations was 7.2
      min (initial visits 7.4 min, follow-up visits 7.1 min). Each computer system cost
      about US$700. The total connection cost for the study was US$4.95. The
      teleconsultations saved the patients US$272 in travel costs. We suggest forming a
      permanent on-line specialist service connected to networked clinics via the
      Internet to improve access to health-care in Croatia.

PMID- 10912338
TI  - An exploratory survey of the applications of telemedicine in Ghana.
AB  - We examined the use of telemedicine at two major medical institutions in Ghana.
      Doctors and administrators were surveyed to assess their knowledge of computers
      and familiarity with telemedicine. The use of modern telecommunications and
      information technology products within the health service was also examined.
      Thirty questionnaires were distributed to staff at the two hospitals, one urban
      and one rural. Twenty were returned (a response rate of 67%). Although most of
      the respondents were computer literate, they were less familiar with telemedicine
      applications. Only a minority of the respondents were participating in an
      information-sharing network, transmitting information by fax or telephone, or had
      Internet access. Financial constraint appeared to be the major barrier to
      establishing information-sharing networks. Other constraints were technological
      and organizational. The respondents expressed an interest in using telemedicine,
      having access to health-care databases and specific telemedicine applications
      such as tele-education and videoconferencing. Staff in the urban hospital were
      more likely to be familiar with telemedicine and more likely to have access to
      information technology than those in the rural hospital.

PMID- 10912339
TI  - Telepsychiatry for post-traumatic stress disorder.

PMID- 10912340
TI  - Finite element analysis of brain contusion: an indirect impact study.
AB  - The mechanism of brain contusion has been investigated using a series of three
      dimensional (3D) finite element analyses. A head injury model was used to
      simulate forward and backward rotation around the upper cervical vertebra.
      Intracranial pressure and shear stress responses were calculated and compared.
      The results obtained with this model support the predictions of cavitation theory
      that a pressure gradient develops in the brain during indirect impact. Contrecoup
      pressure-time histories in the parasagittal plane demonstrated that an indirect
      impact induced a smaller intracranial pressure (-53.7 kPa for backward rotation,
      and -65.5 kPa for forward rotation) than that caused by a direct impact. In
      addition, negative pressures induced by indirect impact to the head were not high
      enough to form cavitation bubbles, which can damage the brain tissue. Simulations
      predicted that a decrease in skull deformation had a large effect in reducing the
      intracranial pressure. However, the areas of high shear stress concentration were
      consistent with those of clinical observations. The findings of this study
      suggest that shear strain theory appears to better account for the clinical
      findings in head injury when the head is subjected to an indirect impact.

PMID- 10912341
TI  - A spot check for estimating stereophotogrammetric errors.
AB  - Good practice rules in the management of a movement analysis laboratory recommend
      that photogrammetric measurement errors are assessed, prior to every experimental
      session, using an ad hoc experiment referred to as a spot check. The paper
      proposes an inexpensive and easy to make spot check. The test uses a rigid rod
      carrying two markers and a target point taken on the line joining them and
      coinciding with the rod tip. The latter point is placed in a fixed and measured
      position in the laboratory frame and the markers are tracked while the rod is
      kept stationary and while it is manually made to rotate about the target point.
      Several target points are used within the measurement volume. The instantaneous
      errors with which the laboratory co-ordinates of the latter points are
      reconstructed are determined and submitted to statistical analysis. A
      normalisation procedure is illustrated that aims at making the test results
      independent from the geometry of the test object. The experimental and analytical
      methods underlying the proposed spot check were validated experimentally in two
      movement analysis laboratories using repeated tests. A rod, 1.5 m long, carrying
      four markers was used. In this way, several test-object geometries were tested.
      Results confirmed that the photogrammetric error could be divided into a zero
      mean random and a systematic component. It was shown that the normalisation
      procedure was effective for the standard deviation of both error components when
      the two markers were located at a distance between them 1.5 times larger than the
      distance of their centroid from the tip of the rod. The systematic component bias
      could not be normalised, however a conservative value of it could be estimated.
      The two above-mentioned normalised standard deviations and the bias value can be
      taken as descriptors of the photogrammetric error of the specific measuring
      system tested. These parameters may also be used to assess the precision and the
      accuracy with which the laboratory position of a target point, defined relative
      to any specified marker cluster, may be reconstructed during movement analysis.

PMID- 10912342
TI  - Effectiveness of supplemental grasp-force feedback in the presence of vision.
AB  - Previous studies have shown that supplemental grasp-force feedback can improve
      control for users of a hand prosthesis or neuroprosthesis under conditions where
      vision provides little force information. Visual cues of force are widely
      available in everyday use, however, and may obviate the utility of supplemental
      force information. The purpose of the present study was to use a video-based hand
      neuroprosthesis simulator to determine whether grasp-force feedback can improve
      control in the presence of realistic visual information. Seven able-bodied
      subjects used the simulator to complete a simple grasp-and-hold task while
      controlling and viewing pre-recorded, digitised video clips of a neuroprosthesis
      user's hand squeezing a compliant object. The task was performed with and without
      supplemental force feedback presented via electrocutaneous stimulation. Subjects
      had to achieve and maintain the (simulated) grasp force within a target window of
      variable size (+/- 10-40% of full scale). Force feedback improved the success
      rate significantly for all target window sizes (8-16%, on average), and improved
      the success rate at all window sizes for six of the seven subjects. Overall, the
      improvement was equivalent functionally to a 35% increase in the window size.
      Feedback also allowed subjects to identify the direction of grasp errors more
      accurately, on average by 10-15%. In some cases, feedback improved the failure
      identification rate even if success rates were unchanged. It is thus concluded
      that supplemental grasp-force feedback can improve grasp control even with access
      to rich visual information from the hand and object.

PMID- 10912343
TI  - An artificial grasping evaluation system for the paralysed hand.
AB  - Neuromuscular electrical stimulation (NMES) has been used in upper limb
      rehabilitation towards restoring motor hand function. Quantitative evaluation of
      the artificially generated movement is necessary to achieve proper muscle
      activation. Custom-made gloves instrumented with force and position transducers
      were used to evaluate artificial quadriplegic grasping for a drinking activity.
      In spite of different sensor position, stimulation parameter dependence and lack
      of repeatability, grasp patterns achieved with the application of NMES follow the
      same patterns previously obtained with normal subjects, regarding force
      distribution among fingers and the shape of force curves. Larger forces were
      exerted by the thumb (average ranged from 2.8 to 4.5 N) following by index or
      long finger (average ranged from 1.8 to 3 N). The forces exerted ranged within
      the same interval as those previously measured and were sufficient to grasp an
      object of 10 N. Finger position achieved by interphalangeal joint status
      indicated the opening size of the hand throughout the range of movement. The
      instrumented gloves offer an alternative force and position feedback system for
      use in cylindrical grasp evaluation. The gloves can be used in a closed-loop
      control system, allowing on-line adjustment or in a clinical application to
      evaluate the results of a rehabilitation programme.

PMID- 10912344
TI  - New prototype NIRS instrument [corrected] to investigate multi-regional cerebral
      blood and tissue oxygenation and haemodynamics.
AB  - Near infra-red spectroscopy (NIRS) is a non-invasive optical technique used to
      assess blood and tissue oxygenation and haemodynamics in living tissue. It is
      presently used as a semi-continuous monitoring technique on a research basis.
      Multi-regional NIRS information could be beneficial for a better understanding of
      the development of cerebral injuries and the reduction of neurodevelopmental
      abnormalities in the human newborn. The paper presents the conversion of the
      continuous wave NIRS single-channel instrument (NIRDCU) into a prototype four
      channel instrument which can be used to provide continuous multi-regional
      information regarding the cerebral blood oxygenation and haemodynamics in the
      frontal, left parietal, right parietal and occipital region of the neonatal
      brain. This has been achieved by attaching an optical multiplexing system to the
      NIRDCU to select different transmitting and receiving fibres, thus addressing
      different regions in the brain. Preliminary laboratory tests on a phantom and on
      the adult forearm are presented, illustrating the practicality of regional
      monitoring.

PMID- 10912345
TI  - Influence of measurement noise and electrode mislocalisation on EEG dipole-source
      localisation.
AB  - Measurement noise in the electro-encephalogram (EEG) and inaccurate information
      about the locations of the EEG electrodes on the head induce localisation errors
      in the results of EEG dipole source analysis. These errors are studied by
      performing dipole source localisation for simulated electrode potentials in a
      spherical head model, for a range of different dipole locations and for two
      different numbers (27 and 148) of electrodes. Dipole source localisation is
      performed by iteratively minimising the residual energy (RE), using the simplex
      algorithm. The ratio of the dipole localisation error (cm) to the noise level (%)
      of Gaussian measurement noise amounts to 0.15 cm/% and 0.047 cm/% for the 27 and
      148 electrode configurations, respectively, for a radial dipole with 40%
      eccentricity The localisation error due to noise can be reduced by taking into
      account multiple time instants of the measured potentials. In the case of random
      displacements of the EEG electrodes, the ratio of dipole localisation errors to
      electrode location errors amounts to 0.78 cm-1 cm and 0.27 cm-1 cm for the 27 and
      148 electrode configurations, respectively. It is concluded that it is important
      to reduce the measurement noise, and particularly the electrode mislocalisation,
      as the influence of the latter is not reduced by taking into account multiple
      time instants.

PMID- 10912346
TI  - Detection and multichannel SVD-based filtering of trigeminal somatosensory evoked
      potentials.
AB  - Very weak and noisy trigeminal somatosensory evoked potentials (TSEPs) are
      considered, which are successfully evoked by electrical stimulation of the
      trigeminal nerve of 15 patients with endosseous oral implants. As TSEP analysis
      provides an objective means of assessing neuronal function, it is considered to
      be a promising tool for investigating tactile sensation through anchoring
      implants in bone. For this purpose, a study of TSEP signals acquired from
      patients with endosseous oral implants has been carried out. Since TSEPs are
      severely contaminated by background ongoing electrical activities of the brain, a
      methodology is developed for statistically detecting the transient signal (TSEP)
      in the biological noise (EEG). For nine out of 15 patients, transient signals are
      detected in the background EEG activity. The TSEPs of these nine patients are
      subjected to further analysis. A multichannel singular value decomposition (SVD)
      based filtering method is applied which successfully separates out the most
      energetic TSEPs from the background EEG, thereby increasing significantly the SNR
      of the recorded signals and improving extraction of the characteristic components
      of the TSEPs. It is shown that the most prominent feature of the TSEP signals for
      patients with endosseous oral implants is a wave with peak latency between 9 and
      15 ms, generally followed by a wave between 25 and 28 ms or 34 and 38 ms for the
      specific cortical response areas.

PMID- 10912347
TI  - An alpha modulation index for electroencephalographic studies using complex
      demodulation.
AB  - An automated technique for measuring the relative amount of amplitude modulation
      of electroencephalographic (EEG) alpha activity is developed to increase the
      number of existing tools for differentiating the various types of alpha activity.
      EEG data collected from 12 normal males is used to characterize alpha modulation
      frequency characteristics. From these findings, a complex demodulation method is
      constructed to extract the amplitude modulation envelope of alpha activity from
      an epoch of EEG data while disregarding both continuous amplitude alpha activity
      and activity outside the alpha band. A threshold technique is then used to
      determine the relative amount of modulation contained within the data epoch. This
      metric is termed the alpha modulation index (AMI). Good correlation (R2 = 0.86)
      is found when automated scoring results are compared with manual scoring of
      physiologic EEG alpha modulation. The flexibility of this technique makes it
      easily adaptable to other EEG frequency bands and applications.

PMID- 10912348
TI  - Two-dimensional Chebyshev pseudospectral modelling of cardiac propagation.
AB  - Bidomain or monodomain modelling has been used widely to study various issues
      related to action potential propagation in cardiac tissue. In most of these
      previous studies, the finite difference method is used to solve the partial
      differential equations associated with the model. Though the finite difference
      approach has provided useful insight in many cases, adequate discretisation of
      cardiac tissue with realistic dimensions often requires a large number of nodes,
      making the numerical solution process difficult or impossible with available
      computer resources. Here, a Chebyshev pseudospectral method is presented that
      allows a significant reduction in the number of nodes required for a given
      solution accuracy. The new method is used to solve the governing nonlinear
      partial differential equation for the monodomain model representing a two
      dimensional homogeneous sheet of cardiac tissue. The unknown transmembrane
      potential is expanded in terms of Chebyshev polynomial trial functions and the
      equation is enforced at the Gauss-Lobatto grid points. Spatial derivatives are
      obtained using the fast Fourier transform and the solution is advanced in time
      using an explicit technique. Numerical results indicate that the pseudospectral
      approach allows the number of nodes to be reduced by a factor of sixteen, while
      still maintaining the same error performance. This makes it possible to perform
      simulations with the same accuracy using about twelve times less CPU time and
      memory.

PMID- 10912349
TI  - Validation of real-time continuous perfusion measurement.
AB  - Perfusion, the rate at which blood in tissue is replenished at the capillary
      level, is a primary factor in the transport of heat, drugs, oxygen and nutrients.
      While there have been many measurement techniques proposed, most do not lend
      themselves to routine, continuous and real-time use. A minimally invasive probe,
      called the thermal diffusion probe (TDP), which uses a self-heated thermistor to
      measure absolute perfusion continuously and in real time, was validated at low
      flows with the microsphere technique. In 27 rabbits, simultaneous TDP
      measurements were made in liver from 0 to 60 ml min-1 100 g-1. The TDP perfusion
      correlated well with the microspheres (R2 = 0.898) and the agreement between
      techniques is very good with a slope close to unity (0.921) and an intercept
      close to zero (0.566 ml min-1 100 g-1). Variability between the two techniques
      was primarily due to the sampling error from the microsphere 'snap shot' of
      periodic blood flow when compared with the continuous TDP perfusion measurement.
      The ability to quantify local perfusion continuously and in real time may have a
      profound impact on patient management in a number of clinical areas such as organ
      transplantation, neurosurgery, oncology and others, in which quantitative
      knowledge of perfusion is of value.

PMID- 10912350
TI  - 3D micro-computed tomography of trabecular and cortical bone architecture with
      application to a rat model of immobilisation osteoporosis.
AB  - Bone mass and microarchitecture are the main determinants of bone strength. Three
      dimensional micro-computed tomography has the potential to examine complete bones
      of small laboratory animals with very high resolution in a non-invasive way. In
      the presented work, the proximal part of the tibiae of hindlimb unloaded and
      control rats were measured with 3D MicroCT, and the secondary spongiosa of the
      scanned region was evaluated using direct evaluation techniques that do not
      require model assumptions. For determination of the complete bone status, the
      cortex of the tibiae was evaluated and characterised by its thickness. It is
      shown that with the proposed anatomically conforming volume of interest (VOI), up
      to an eight-fold volume increase can be evaluated compared to cubic or spherical
      VOIs. A pronounced trabecular bone loss of -50% is seen after 23 days of tail
      suspension. With the new evaluation techniques, it is shown that most of this
      bone loss is caused by the thinning of trabeculae, and to a lesser extent by a
      decrease in their number. What changes most radically is the structure type: the
      remaining bone is more rod-like than the control group's bone. Cortical bone
      decreases less than trabecular bone, with only -18% after 23 days.

PMID- 10912351
TI  - Anisotropy of Young's modulus of human tibial cortical bone.
AB  - The anisotropy of Young's modulus in human cortical bone was determined for all
      spatial directions by performing coordinate rotations of a 6 by 6 elastic
      stiffness matrix. The elastic stiffness coefficients were determined
      experimentally from ultrasonic velocity measurements on 96 samples of normal
      cortical bone removed from the right tibia of eight human cadavers. The following
      measured values were used for our analysis: c11 = 19.5 GPa, c22 = 20.1 GPa, c33 =
      30.9 GPa, c44 = 5.72 GPa, c55 = 5.17 GPa, c66 = 4.05 GPa, c23 = 12.5 GPa. The
      remaining coefficients were determined by assuming that the specimens possessed
      at least an orthorhombic elastic symmetry, and further assuming that c13 = c23
      c12 = c11 - 2c66. Our analysis revealed a substantial anisotropy in Young's
      modulus in the plane containing the long axis of the tibia, with maxima of 20.9
      GPa parallel to the long axis, and minima of 11.8 GPa perpendicular to this axis.
      A less pronounced anisotropy was observed in the plane perpendicular to the long
      axis of the tibia. To display our results for the full three-dimensional
      anisotropy of cortical bone, a closed surface was used to represent Young's
      modulus in all spatial directions.

PMID- 10912352
TI  - Modelling of chronic wound healing dynamics.
AB  - Following chronic wound area over time can give a general overview of wound
      healing dynamics. Decrease or increase in wound area over time has been modelled
      using either exponential or linear models, which are two-parameter mathematical
      models. In many cases of chronic wound healing, a delay of healing process was
      noticed. Such dynamics cannot be described solely with two parameters. The
      reported study deals with two-, three-, and four-parameter models. Assessment of
      the models was based on weekly measurements of 226 chronic wounds of various
      aetiologies. Several quantitative fitting criteria, i.e. goodness of fit,
      handling missing data and prediction capability, and qualitative criteria, i.e.
      number of parameters and their biophysical meaning were considered. The median of
      goodness of fit of three- and four-parameter models was between 0.937 and 0.958,
      and the median of two-parameter models was 0.821 to 0.883. Two-parameter models
      fitted wound area over time significantly (p = 0.01) worse than three- and four
      parameter models. The criterion handling missing data provided similar results,
      with no significant difference between three- and four-parameter models. Median
      prediction error of two-parameter models was between 111 and 746; three-parameter
      models resulted in an error of 64 to 128, and finally four-parameter models
      resulted in the highest prediction error of 407 and 238. Based on the values of
      quantitative fitting criteria obtained, three parameters were chosen as the most
      appropriate. Based on qualitative criteria, the delayed exponential model was
      selected as the most general three-parameter model. It was found to have good
      prediction capability and in this capacity it could be used to help physicians
      choose the most appropriate treatment for patients with chronic wounds after an
      initial three-week observation period, when the median error increase of fitting
      is 74%.

PMID- 10912353
TI  - Numerical model of deep venous thrombosis detection using venous occlusion strain
      gauge plethysmography.
AB  - Strain gauge plethysmography (SGP) is a non-invasive method used in the detection
      of deep venous thrombosis (DVT). The technique is based on the measurement of
      calf volume changes in response to venous occlusion by a thigh cuff, the volume
      changes reflecting the rates of arterial inflow and venous outflow. A numerical
      model of the blood circulation within the limb and the response of this to a SGP
      test has been derived, based on treating the different parts of the circulatory
      system in the leg as resistance and capacitance elements. The simulation results
      were compared with clinical studies and support the ability of SGP to detect non
      occlusive clots of more than 50-60% of the lumen, as well detecting calf vein
      occlusion. The non-linear behaviour of the venous compliance with intra-luminal
      pressure appears to be a particularly important factor within the model. In
      addition, increases in venous tone due to post-operative venospasm were shown to
      be a potential source of false positive results.

PMID- 10912354
TI  - Influence of the size of syncytial units on synaptic potentials in smooth muscle.
AB  - The effect of the size of syncytial bundles of cells on the passive synaptic
      potentials generated within them has been explored. Computer simulations have
      been performed of neuronally produced spontaneous excitatory junction potentials
      (SEJPs) generated in cubical 'bidomain' model of syncytial tissue. It is found
      that indical properties of SEJPs vary conspicuously in syncytium sizes smaller
      than about 15-17-cube, but change very little in syncytium sizes greater than
      this. At the centroid of the cube, the peak amplitude Vp of the SEJP declines
      from 14.32 mV to 11.70 mV as syncytium size increases from 7-cube to 15-cube,
      i.e. a decrease of approximately 18%, while between system sizes 15-cube (Vp =
      11.70 mV) and 29-cube (Vp = 11.67 mV), the reduction is only approximately 0.3%.
      Similar trends are observed for the time to peak of SEJPs. These observations
      indicate a minimum bundle size in smooth muscle below which syncytial function is
      modified; the implications of this are discussed.

PMID- 10912356
TI  - Occupational medicine and the pursuit of quality.

PMID- 10912355
TI  - Spreading and motility of human glioblastoma cells on sheets of silicone rubber
      depend on substratum compliance.
AB  - Although there is a substantial quantity of experimental data examining the
      effects of adhesion on the morphology and migration of tissue cells, little
      attention has been focused on how changes in substratum mechanical properties
      affect these cellular behaviours. To determine whether the ability of a
      substratum mechanically to support traction influences cell morphology and
      motility, measurements are taken of the spreading, the fraction of a population
      with pseudopodia, the number of pseudopodia and the translocation of human SNB-19
      glioblastoma cells cultured on films of poly(methylphenyl)siloxane possessing a
      range of mechanical compliances. Cells cultured on these films generate
      deformations (i.e. 'wrinkles') that are used as a basis to estimate effective
      substratum compliances. The average projected cell area decreases by over 60%,
      with a two-orders-of-magnitude increase in compliance. Time-lapse videomicroscopy
      reveals that cell migration also decreases with increasing compliance: the
      average cell speed decreases from approximately 8 microns h-1 on the most rigid
      substrata to 1.2 microns h-1 on the most compliant substrata examined. Changes in
      compliance do not alter mean directional persistence time. These results are
      interpreted in terms of the predictions of mathematical models for the effects of
      substratum compliance on motility.

PMID- 10912357
TI  - An economic evaluation of occupational health.
AB  - There is an increasing need to evaluate the costs and benefits of an occupational
      health service (OHS). However, measuring benefits from an OHS is inherently
      difficult. Instead, an economic model can be constructed to present the minimum
      threshold benefits required for OHSs to be cost-effective, given what is known
      about costs. This model assumes that the benefits of an OHS are to maximize
      health and morale of employees; maximize performance and increase productivity;
      minimize medico-legal costs; enhance workplace safety; and reduce sickness
      absence. A certain distribution across these benefits can be assumed for each
      OHS. The overall required value of all benefits brought about by use of an OHS is
      in the range 158-199 Pounds per year. The plausibility of results can be assessed
      using known data and judgement. Despite many uncertainties it is likely that the
      minimum benefit thresholds will be achieved overall.

PMID- 10912358
TI  - A survey of the use of post-exposure prophylaxis for occupational exposure to
      human immunodeficiency virus.
AB  - The objective of this study was to review the appropriateness of the use of post
      HIV exposure prophylaxis for incidents involving occupational exposure to body
      fluids. The design was a retrospective analysis of the 32 incidents for which at
      least one dose of post-exposure prophylaxis was given, reported to the
      occupational health department of a London teaching hospital between 20 August
      1997 and 20 January 1999. The main outcome measures were the proportion of
      prescriptions for exposure to a known HIV positive source, and criteria for
      prescribing when the source patient's HIV status was unknown. Only 31% of
      prescriptions were for exposure to a known HIV positive source. The reasons for
      prescribing post-exposure prophylaxis in the other 69% of cases were unclear.
      Safety data for short courses of anti-retroviral drugs in this setting could help
      to assess the appropriateness of their use to allay anxiety in healthcare
      workers, pending clarification of the source patient's HIV status. Closer
      collaboration between departments and more detailed guidance would improve
      consistency of practice, and may save some unnecessary prescriptions for
      expensive and toxic drugs.

PMID- 10912359
TI  - Does vacation enable recuperation? Changes in well-being associated with time
      away from work.
AB  - The objective of this paper was to study the change of well-being associated with
      vacation and the effect of vacation related variables on these changes. Fifty
      three employees (16 women, 37 men) of a medium sized aluminium hardware
      manufacturer in Austria participated. Measures were taken 10 days before and 3
      days after vacation. A small follow-up group at 5 weeks post-vacation was
      included. Three days after vacation, physical complaints, the quality of sleep
      and mood had improved as compared to before vacation. Average life satisfaction
      did not change during vacation. Five weeks after vacation subjects still reported
      less physical complaints than before vacation. The experienced recuperation
      during vacation explained 56% of the variance regarding the change of well-being.
      Moderating variables of recuperation were the amount of personally available time
      and vacation satisfaction. Furthermore, the number of stressful days at home were
      associated negatively, while the number of non-stressful days at home and the
      number of days away from home correlated moderately positively with recuperation.
      The study indicates that vacation may improve well-being on a short term basis.

PMID- 10912360
TI  - Air blast circuit breaker noise and hearing loss: a multifactorial model for risk
      assessment.
AB  - The assessment of the risk to hearing from impulse noise exposure may be a
      problem for the occupational physician because existing legislative and
      international noise exposure standards deal primarily with continuous noise, and
      are not valid in excess of the peak exposure limit of 200 pa (140 dB). Noise
      exposure in excess of this level, for example that due to firearms, is frequently
      perceived as harmful, but this is not necessarily the case, as impulse noise
      standards do, in fact, allow exposure with a maximum in the order of 6.3 kPa (170
      dB). To illustrate this, a cross-sectional group of electrical transmission
      workers have been studied who were exposed to significant levels of impulse noise
      from air blast circuit breakers and firearms. Important hearing loss factors have
      been identified by means of a specially designed questionnaire. Using the Health
      & Safety Executive definition, the risk of hearing loss was determined by
      calculating prevalence odds ratios (ORs) for exposure to these factors. The OR
      for those with fewer than eight unprotected air blast circuit breaker exposures
      was 2.27 (95% confidence interval (CI), 1.01-5.08), whilst for those with more
      than eight exposures the OR was 2.10 (95% CI, 0.97-4.54). For firearm exposure,
      ORs of 1.61 (95% CI, 0.95-2.74) were noted in the medium exposure group and 2.05
      (95% CI, 1.08-3.86) in the high exposure group. When all the factors were
      included in the model, the most significant factor was age. The study gives
      support to the impulse noise exposure criteria, confirming the borderline risk
      from air blast circuit breaker noise exposure and the relative safety of moderate
      gunfire exposure.

PMID- 10912361
TI  - Surveillance on self-report: a trial of health and safety monitoring in
      occupational settings.
AB  - A method for monitoring health and safety in the workplace, referred to as
      'surveillance on self-report', is presented. This occupational health and safety
      monitoring method consists of a collection of data on certain aspects of health
      and safety obtained by dispensing self-administered questionnaires to employees
      or managers and supervisors in workplaces, and administering regular feedback on
      the responses. Based on the responses, a continual monitoring and improvement on
      certain aspects of health and safety were possible in two workplaces in New
      Zealand. This study has shown a methodology for the surveillance of hazard
      control and monitoring, injuries and illnesses, and organizational policies in
      occupational settings.

PMID- 10912362
TI  - Aggression in boat builders: a search for altered mood states in boat builders
      exposed to styrene.
AB  - Published reviews and industrywide anecdotal reports have suggested an
      association between exposure to some volatile organic compounds (VOCs) and
      altered mood states. In this paper we report a unique study of boat-builders
      exposed to styrene. Two hundred and thirteen employees exposed to solvents and
      144 who were not exposed completed questionnaires related to mood states.
      Additionally, for 23 of the 213 employees, the air concentrations of styrene were
      measured at their workplaces, and urinary concentrations of mandelic acid (a
      metabolite of styrene) were determined in order to assess biological exposure.
      Special features of this study included the use of the Prolife of Mood States
      (POMS) questionnaire and the availability of sound historical data. A weak
      association is demonstrated between styrene exposure and aggression/hostility.
      That this is found to be most marked in the earliest years of exposure suggests
      that selection characteristics might be a more important association than solvent
      exposure.

PMID- 10912363
TI  - A survey of eye trauma and diseases at a teaching hospital: implications for
      training in occupational ophthalmology in Nigeria.
AB  - This study explores the amount of occupational ophthalmology that it is possible
      to encounter within an existing teaching hospital system, as this offers the
      primary training facilities for resident doctors who expect to specialize in
      occupational medicine. The study was based on an analysis of ophthalmology
      patient records available at the University College Hospital, Ibadan, which is
      Nigeria's largest teaching hospital. One thousand, three hundred and thirty-four
      patients with eye disease were seen during the 1-year study. Of these, 1052
      (78.9%) did not have their occupations recorded. Accidents were the only
      occupational diagnoses recorded, and this occurred in 75 (5.6%) of cases. The
      findings indicate that doctors who train in this specialty should gain experience
      in industries that have sizeable occupational health services, in addition to
      their formal ophthalmology training, in order to acquire experience in primary
      and occupational eye care. It is suggested that greater emphasis be placed on
      occupational ophthalmology in teaching hospitals and that there is a general
      improvement in completing patients' records: in particular, a patient's
      occupation should be recorded.

PMID- 10912364
TI  - How do you manage dermatitis after exposure to the causative agent has ceased?
AB  - Contact dermatitis may not clear completely when the cause of the problem is
      removed, and in some cases continues long after the causal occupation has been
      given up. This paper outlines some methods of managing the problem.

PMID- 10912365
TI  - New stressors, new remedies.
AB  - This paper looks at the stressors prominent in the workplace at the end of the
      20th century--increases in workload, falls in social support, uncertainty and
      violence. It considers some of the pressures that have created these stressors
      and some of the interventions used to combat them; for example, better
      teamworking, different management style, an emphasis on quality, a more accurate
      analysis of the burgeoning costs of stress to organizations, and an increasing
      appreciation that parental stress affects children negatively and so makes our
      future society more at risk. It considers the rising emphasis on the individual
      role in stress, and on the increase in counselling services. It concludes that
      occupational health services have a very important role to play not only in
      providing secondary interventions but also in influencing preventive measures.

PMID- 10912366
TI  - Nasal lavage in woodworkers.

PMID- 10912367
TI  - Do health checks cause stress.

PMID- 10912368
TI  - Evidence-based occupational medicine: the good, the bad and the otherwise
      difficult.

PMID- 10912369
TI  - Occupational and environmental medicine: sustainable development?
AB  - Occupational medicine is evolving to meet the needs of the 21st century. There is
      a need to define the remit of occupational and environmental medicine in order to
      facilitate the development and maintenance of requisite competencies, the
      establishment of educational goals for practitioners and production of a
      professional product for the global market place. The delivery of occupational
      health services will be underpinned by quality assurance systems.

PMID- 10912370
TI  - Occupational and environmental medicine: moving the factory fence or hedging our
      bets?
AB  - Occupational and environmental medicine evolved out of concern for the effect of
      work hazards on health. The experienced gained in considering such hazards has
      been extended to understanding general risks in the environment. As we look
      toward the future, classical occupational and environmental hazards such as over
      exposure to lead, asbestos and mercury are waning and being replaced by concerns
      around sustainable development, toxicology testing and exposure information for
      high production volume chemicals, development of better approaches for setting
      workplace and community exposure limits, environmental justice and many others.
      The opportunities for the future exist in overcoming these new challenges.

PMID- 10912371
TI  - Major chemical incidents: bridging the occupational--public health gap.
AB  - Increasing awareness and concern about possible long-term health effects of
      exposure to chemicals after major chemical incidents has opened up a new area of
      public health activity. However, progress is hampered by a lack of low level
      exposures in potentially highly susceptible subgroups of the populations, and by
      a lack of expertise in public health. The challenge is to extend the
      toxicological and epidemiological experience developed in the occupational
      setting to the community level. To better define the problem population
      surveillance of acute chemical hazards, first set up in Wales, has been extended
      throughout the UK, and is also being piloted internationally. Further work is
      needed to address specific problems of the epidemiological follow-up of
      populations exposed, the assessment of the psychological consequences at the
      community level, and risk perception and communication. Organisational
      arrangements for the public health management of incidents and their sequelae
      must move beyond short-term funding and market competition and must incorporate
      the expertise of the occupational disciplines.

PMID- 10912372
TI  - Communicating occupational and environmental issues.
AB  - Effective health risk communication is an important tool that can prevent or
      modify the inappropriate public reactions that often accompany occupational and
      environmental health issues and allegations. The public perception of the
      magnitude or significance of risk is influenced by factors other than scientific
      data. The goal of risk communication therefore is more than just imparting
      scientific facts. It is about ensuring that the public fully understand risk and
      that they are enabled to make informed decisions under conditions of uncertainty.
      How people perceive risk, and their values and feelings toward occupational and
      environmental health issues, are as important considerations for risk
      communication as are numerical or factual scientific data. Occupational and
      environmental health scares often occur because of complexities such as the
      multidimensionality of risk, trust or mistrust in sources of information,
      technological revolution, the reliance of the public on the media for health
      information and the public desire for information and the truth. If, as health
      professionals, we are to address effectively both real and perceived occupational
      and environmental health issues, we need to be aware of the major advances that
      have been made in the use of risk communication in recent years.

PMID- 10912373
TI  - The application of the methods of evidence-based practice to occupational health.
AB  - Evidence-based methods of practice are becoming widely used in many areas of
      healthcare. The techniques of data appraisal, systematic review and meta-analysis
      and their application to clinical and preventative medicine through clinical
      guidelines and economic analyses are well established. These methods have only
      been applied to occupational health risks and interventions in a very limited way
      and there is considerable scope for wider use, especially in the clinical aspects
      of practice. This should improve the quality of prevention and would also enable
      practitioners to give more soundly based advice and to secure their professional
      positions as providers of quality assured information. Human and financial
      resources and commitment to the development of evidence-based approaches by the
      professions and those they work for are pre-requisites for success.

PMID- 10912374
TI  - Symptoms experienced in connection with mobile phone use.
AB  - Many people in Norway and Sweden reported headaches, fatigue, and other symptoms
      experienced in connection with the use of a mobile phone (MP). Therefore, we
      initiated a cross-sectional epidemiological study among 17,000 people, all using
      an MP in their job. Thirty-one percent of the respondents in Norway and 13% of
      those in Sweden had experienced at least one symptom in connection with MP use.
      Next to the sensations of warmth on the ear and behind/around the ear, burning
      sensations in the facial skin and headaches were most commonly reported. Most
      symptoms usually began during or within half an hour after the call and lasted
      for up to 2 h. Relatively few had consulted a physician or been on sick leave
      because of the symptoms, but about 45% among those with an MP attributed symptom
      had taken steps to reduce the symptom. These results suggest an awareness of the
      symptoms, but not necessarily a serious health problem.

PMID- 10912375
TI  - The teaching of occupational and environmental medicine to medical students in
      Australia and New Zealand.
AB  - All the medical schools in Australia and New Zealand were surveyed in order to
      determine the amount of teaching devoted to occupational and environmental
      medicine in the medical courses in 1998. A 100% response rate was achieved. The
      results showed that the number of hours devoted to these topics varied widely,
      but averaged 12.8 h and 10.5 topics. The most significant factor accounting for
      the variability was the presence on the universities' teaching staff of
      individuals trained in the practice of occupational medicine. While our findings
      show a greater time devoted to these topics than those of similar studies in the
      United States and Britain, the absolute time remains small when compared with the
      prevalence of occupational medicine problems in the community. There is little
      congruence in terms of both content and assessment processes between schools.

PMID- 10912376
TI  - Healthy workplace indicators: costing reasons for sickness absence within the UK
      National Health Service.
AB  - Sandwell Healthcare NHS Trust has been developing a tool for monitoring the
      reasons and costs of long-term sick leave (> 7 days). The data obtained from this
      process has been used to modify the type of occupational health and safety
      services provided for the Trust. Adoption of more standardized tools of this
      nature throughout the National Health Service (NHS) would help trusts to compare,
      and where appropriate enhance, the services provided by occupational health.
      Musculo-skeletal and mental health problems, account for the greatest costs
      arising from long-term sickness absence. It may therefore be prudent for NHS
      employers and their occupational health services to target their efforts on these
      particular problems.

PMID- 10912377
TI  - The risk of heat exhaustion at a deep underground metalliferous mine in relation
      to body-mass index and predicted VO2max.
AB  - The risk of heat exhaustion at a deep underground metalliferous mine was assessed
      in relation to the body-mass index (BMI) and predicted maximal oxygen uptake
      (VO2max) of miners, using case-control methodology. Sixty-five cases of acute
      heat exhaustion and 119 controls were studied. Heat exhaustion cases had a
      significantly higher BMI than controls (P = 0.006). The odds ratios increased
      with BMI. For a BMI of 32.00-36.99, compared to a BMI of less than 27.00 the odds
      ratio was 3.63 (95% confidence interval, 1.42-9.36). VO2max was not significantly
      lower in cases than controls. The odds ratios for heat exhaustion increased with
      decreasing VO2max, but not significantly. The sample size provided 80% power of
      detecting an odds ratio of 2.5 or greater. Deep underground miners should be
      advised to maintain a BMI of 24-27. Selection of miners on the basis of BMI
      should not be used as an alternative to satisfactory engineering controls such as
      ventilation and refrigeration.

PMID- 10912378
TI  - Occupational contact dermatitis in the UK: a surveillance report from EPIDERM and
      OPRA.
AB  - Since February 1993 the EPIDERM surveillance scheme has collected data on
      occupational skin disease from consultant dermatologists in the UK. Reporting by
      occupational physicians to the scheme began in May 1994 and was superseded in
      January 1996 by the Occupational Physicians Reporting Activity (OPRA). The
      schemes currently receive reports on incident cases from 244 dermatologists and
      790 occupational physicians. An estimated total of 9937 cases of contact
      dermatitis reported by dermatologists was calculated from surveillance data; 8129
      contact dermatitis cases were estimated from reports by occupational physicians.
      The annual incidence of occupational contact dermatitis from dermatologist
      reports was 6.4 cases per 100,000 workers and 6.5 per 100,000 from reports by
      occupational physicians, an overall rate of 12.9 cases per 100,000 workers.
      Manufacturing industries account for the greatest number of cases seen by both
      sets of reporting physicians, with health care employment second. Reports from
      dermatologists also indicate high rates of dermatitis in the personal service
      industries (mainly hairdressers and barbers) and in agriculture. With the
      exception of an increase in cases seen in nurses in both schemes, the numbers and
      proportions of cases of contact dermatitis within occupations have remained
      fairly constant over the 6-year reporting period. Agents accounting for the
      highest number of allergic contact dermatitis cases were rubber (23.4% of
      allergic cases reported by dermatologists), nickel (18.2), epoxies and other
      resins (15.6), aromatic amines (8.6), chromium and chromates (8.1), fragrances
      and cosmetics (8.0), and preservatives (7.3). Soaps (22.0% of cases), wet work
      (19.8), petroleum products (8.7), solvents (8.0), and cutting oils and coolants
      (7.8) were the most frequently cited agents in cases of irritant dermatitis. The
      national scope of the data, together with the parallel structure by which both
      dermatologists and occupational physicians report incident cases, is useful in
      determining the extent of skin hazards in UK industry and may help in better
      targeting efforts to reduce the burden of skin disease at work.

PMID- 10912379
TI  - What is the risk of noise-induced hearing loss at 80, 85, 90 dB(A) and above?
AB  - Regulations regarding risk from exposure to noise at work entail action at levels
      of 85 dB(A) and above. At 80 dB(A) there is no material risk in the vast majority
      of individuals. At 85 dB(A) there is a marginal risk with susceptible individuals
      accruing a significant hearing impairment from a lifetime of exposure. At 90
      dB(A) and above the risk becomes material, with the majority of individuals
      accruing a significant hearing impairment.

PMID- 10912380
TI  - Ergonomics and occupational medicine: future challenges.
AB  - Ergonomics has come a long way since the birth of the subject some 50 years ago.
      It now has an established research base and an appropriate portfolio of
      methodologies. A brief overview of the subject's development will be presented,
      with a particular focus on the contribution of ergonomics to our understanding of
      work related musculoskeletal disorders. Future challenges are also considered in
      this area, with particular emphasis on the need for a multidisciplinary approach
      to many industrial problems where the ergonomist, occupational physician and
      other professionals are needed to tackle existing and future work problems.
      Additionally, the importance of participatory ergonomics is considered, with
      respect to understanding and advancing solutions in this area. The issues of the
      ageing workforce and the challenges that must be met are also outlined. This area
      again emphasizes the need for a multidisciplinary team approach that is proactive
      and designed to maximize the health and wellbeing of workers at all ages, whilst
      also ensuring a full and productive life.

PMID- 10912381
TI  - Greek street food vending: an old habit turned new.

PMID- 10912382
TI  - Street foods in America--a true melting pot.

PMID- 10912383
TI  - Public (street) foods in Australia.

PMID- 10912384
TI  - Profile of street foods sold in Asian countries.

PMID- 10912385
TI  - Street foods in Africa.

PMID- 10912386
TI  - Street foods in Latin America.

PMID- 10912387
TI  - Sale of street food in Latin America. The Mexican case: joy or jeopardy?
AB  - Have you ever visited a public market in Mexico, Guatemala, Panama, Colombia,
      Venezuela, Peru or Brazil? Have you ever stopped to eat delicious Mayan-style
      pork tacos, turnovers filled with corn fungus or squash flower, octopus stuffed
      crepes, crab, cassava, 'alcapurrias' or grasshoppers with lime juice and chili,
      agave worms or a 'come back to life' seafood cocktail? If you have not, you have
      been missing a large part of the Mexican, Guatemalan, Panamanian, Colombian,
      Venezuelan, Peruvian and Brazilian folklore, taste, smell and color. And if you
      have visited these countries, it will be easier for you to understand the
      information in this chapter.

PMID- 10912388
TI  - Street food vending: the Israeli scenario.

PMID- 10912389
TI  - Vertigo. Taking the spin out of life.

PMID- 10912390
TI  - Health tips. Treating minor burns.

PMID- 10912391
TI  - Disposable hearing aids may offer added convenience.

PMID- 10912392
TI  - If you don't want to break a hip later, exercise now.

PMID- 10912393
TI  - High-protein, low-carb diets. Are they right for you?

PMID- 10912394
TI  - Platelet counts. What it means when they're high or low.

PMID- 10912395
TI  - Acute delirium. It sometimes occurs in a hospital setting.

PMID- 10912396
TI  - How frequently should my bone density be checked if I have osteoporosis?

PMID- 10912397
TI  - I have athlete's foot. How should I treat it?

PMID- 10912398
TI  - Fistula-in-ano after episiotomy.
AB  - BACKGROUND: In the past 2 years, we treated three women with fourth-degree
      lacerations or episiotomy infections presenting with persistent pain and drainage
      not responding to standard treatment. CASES: These women were referred for
      evaluation 5 weeks, 3.5 months, and 2 years postpartum. After diagnosing fistula
      in-ano, we treated them with fistulotomy and curettage, which resolved the
      problem. CONCLUSION: When a patient presents with pain or drainage at her
      episiotomy site, fistula-in-ano should be considered.

PMID- 10912399
TI  - Intermenstrual bleeding secondary to cesarean scar diverticuli: report of three
      cases.
AB  - BACKGROUND: The differential diagnosis of intermenstrual bleeding includes
      structural lesions of the endometrium and cervix. CASES: Discrete diverticuli
      were noted in the endocervical canals of three women presenting with histories of
      multiple cesareans and chief complaints of intermenstrual bleeding. On
      ultrasound, diverticuli were diagnosed as cavities filled with heterogeneous
      material consistent with blood. In one case, the diverticulum was also visualized
      on hysterosalpingogram. Hysterectomy specimens in two cases showed diverticuli
      lined with fibrous tissue in previous uterine scars; in one case, this also
      contained endometrium. CONCLUSION: Uterine scar diverticuli may cause
      intermenstrual bleeding in women with previous cesareans. When performing
      ultrasound in this clinical setting, physicians should look for these defects.

PMID- 10912400
TI  - Hormonal treatment of an endometrial stromal nodule followed by local excision.
AB  - BACKGROUND: Endometrial stromal nodule is a rare subtype of endometrial stromal
      tumor. Although such nodules are benign, hysterectomy has been considered the
      treatment of choice, because evaluation of the margin is required for diagnosis.
      The similarity between low-grade stromal sarcoma and stromal nodule suggests that
      stromal nodules might respond to hormonal management. CASE: Twenty-one-year-old
      nulligravida, diagnosed with endometrial stromal nodule, which decreased in size
      with leuprolide acetate treatment, underwent local excision of the tumor with
      preservation of reproductive function. CONCLUSION: Hormonal therapy was
      successful in decreasing the size of this stromal nodule which allowed for
      conservative management.

PMID- 10912401
TI  - Port-site recurrence after laparoscopic surgery for endometrial carcinoma.
AB  - BACKGROUND: Women with endometrial carcinoma are being treated with laparoscopic
      surgery, but the risk of port-site recurrences remains undefined. CASE: A 58-year
      old woman underwent laparoscopically assisted vaginal hysterectomy, bilateral
      salpingo-oophorectomy, and laparoscopic lymphadenectomy for endometrial cancer.
      Final surgical stage was IA, with grade 2 histology. Twenty-one months later, she
      developed a 5-cm recurrent tumor mass at a lateral laparoscopic port site. The
      mass was resected, and a restaging laparotomy performed, without evidence of
      other metastases. Radiation therapy was administered to the involved anterior
      abdominal wall. Two and one half years later, there is no evidence of recurrence.
      CONCLUSION: An isolated laparoscopic port-site recurrence might be attributable
      to the initial laparoscopic management of an otherwise good-prognosis endometrial
      carcinoma.

PMID- 10912402
TI  - Spontaneous ovarian hyperstimulation and primary hypothyroidism with a naturally
      conceived pregnancy.
AB  - BACKGROUND: Ovarian hyperstimulation syndrome, not related to ovulation
      induction, is rare. A MEDLINE search from 1987 to 1997 using the key words
      "spontaneous ovarian stimulation," "pregnancy," and "hypothyroidism" revealed
      only five cases: three associated with pregnancies and two with primary
      hypothyroidism. CASE: A 25-year-old white gravida 2, para 1, at 11-12 weeks'
      gestation presented with mild distension of a nontender abdomen, myxedematous
      facies, and large bilateral, multilobulated ovarian cysts. Conception had
      occurred spontaneously. Thyroid stimulating hormone was elevated, and free
      triiodothyronine and free thyroxine were low. Hypothyroidism, associated with
      spontaneous ovarian hyperstimulation syndrome, was diagnosed, and oral
      levothyroxine (0.10 mg/day) was started. With TSH still elevated at 21 weeks,
      levothyroxine was increased to 0.20 mg/day, and by 24 weeks, TSH and ovarian size
      were normal. Vaginal delivery of a 1120 g male infant occurred at 28 weeks.
      CONCLUSION: A case of naturally conceived pregnancy associated with spontaneous
      ovarian hyperstimulation and primary hypothyroidism is reported.

PMID- 10912404
TI  - Pregnancy in women with Noonan syndrome: report of two cases.
AB  - BACKGROUND: Noonan syndrome is similar phenotypically to Turner syndrome,
      accounting for one in 1000-2500 live births. Two thirds of patients have cardiac
      anomalies, half with pulmonary stenosis. Two cases of Noonan syndrome in
      pregnancy are presented, each woman with a different cardiac anomaly. CASES: The
      first patient sought preconception counseling for pulmonary stenosis. She
      conceived within a year and had a cesarean because of prolonged rupture of
      membranes, transverse lie, and variable decelerations. The second patient
      presented at 14 weeks' gestation with an unrepaired coarctation of the aorta. She
      had an assisted vaginal delivery at 38 weeks. CONCLUSION: Successful pregnancy
      was possible in women with Noonan syndrome. A coordinated multidisciplinary team
      approach improved the likelihood of a successful outcome.

PMID- 10912403
TI  - Acute fatty liver in the second trimester.
AB  - BACKGROUND: Acute fatty liver of pregnancy is a rare, potentially fatal disease
      that occurs in the late third trimester or early postpartum period. The case of a
      woman with acute fatty liver in the second trimester is presented. CASE: A 35
      year-old woman, gravida 5, para 4, presented at 22 weeks' gestation with nausea,
      vomiting, malaise, weight loss, and moderately elevated liver transaminase
      levels. The differential diagnoses included viral gastroenteritis and
      cholelithiasis. During the next 12 days, her transaminase levels increased,
      jaundice developed, her sensorium changed, and coagulopathy appeared. After the
      patient was transferred to a tertiary care hospital, acute fatty liver of
      pregnancy was diagnosed. The woman rapidly improved after delivery. CONCLUSION:
      Although acute fatty liver of pregnancy usually occurs in the late third
      trimester or early postpartum period, it can occur in the second trimester.

PMID- 10912405
TI  - Neurocysticercosis in pregnancy: a case initially diagnosed as eclampsia.
AB  - BACKGROUND: Neurocysticercosis is an infection of the central nervous system with
      the pork tapeworm's cysticercus. CASE: A 21-year-old Hispanic primigravida
      presented at 33 weeks' gestation with acute onset of mental status changes
      preceded by headaches and emesis. She was transferred comatose to our institution
      with a diagnosis of postictal state secondary to eclampsia. Upon arrival, the
      patient developed anisocoria, papilledema, posturing, and hypertension.
      Neuroimaging showed an intraventricular cyst. The patient was treated with
      ventriculostomy, induction of labor, postdelivery shunting, albendazole, and
      prednisone. CONCLUSION: Neurocysticercosis should be considered in the
      differential diagnosis of pregnant patients with coma and/or seizures, especially
      if the patient has emigrated from or traveled to an endemic area. Albendazole,
      with shunt procedure, is the treatment of choice for intraventricular
      neurocysticercosis.

PMID- 10912406
TI  - Libman-Sacks endocarditis in a pregnant woman with acute respiratory distress
      syndrome.
AB  - BACKGROUND: Sterile fibrinous vegetations on the mitral valve (Libman-Sacks
      endocarditis) might be found in one-third of patients with antiphospholipid
      antibodies. Usually of minor hemodynamic significance, these vegetations might
      complicate acute respiratory distress syndrome in pregnancy. CASE: Despite
      delivery and aggressive medical therapy, a 17-year-old primigravida with
      pyelonephritis and acute respiratory distress syndrome suffered rapid
      decompensation. Echocardiography showed mitral valve vegetations with severe
      regurgitation. Blood cultures were negative, but antinuclear antibody test and
      lupus anticoagulant were positive. The patient died of massive cerebral
      infarction and brainstem herniation. Autopsy found a patent foramen ovale and
      Libman-Sacks endocarditis. CONCLUSION: With rapid decompensation of acute
      respiratory distress syndrome in pregnancy, despite aggressive medical therapy,
      complicating processes must be considered, especially with antiphospholipid
      antibodies, which can be associated with sterile heart vegetations and subsequent
      fatal thromboembolism.

PMID- 10912407
TI  - Diffusion-weighted images and vasogenic edema in eclampsia.
AB  - BACKGROUND: In eclampsia, it is mandatory to recognize specific cerebrovascular
      complications before initiation of treatment. Diffusion-weighted magnetic
      resonance imaging (MRI) is a new technique that differentiates between cerebral
      infarction and hypertensive encephalopathy with vasogenic edema. CASE: A 23-year
      old primigravida developed eclampsia at 29 weeks' gestation. Focal neurologic
      signs and neuroimaging findings by computed tomography and MRI were consistent
      with acute infarction or vasogenic edema. Diffusion-weighted MRI did not show an
      abnormal signal, indicating vasogenic edema. Control of the severe hypertension
      without anticoagulation therapy was begun. After delivery, the woman's neurologic
      abnormalities disappeared. CONCLUSION: Diffusion-weighted MRI differentiated
      between cerebral infarction and vasogenic edema, helping in the management of
      eclampsia.

PMID- 10912408
TI  - The ex utero intrapartum treatment procedure for a large fetal neck mass in a
      twin gestation.
AB  - BACKGROUND: Large fetal neck masses can make it difficult or impossible to secure
      airways at birth, with associated risks of hypoxia, brain injury, and death.
      Based on a MEDLINE search from 1966 to June 1998, using the keywords EXIT
      procedure, placental support, twins, and neck mass, we report the first ex utero
      intrapartum treatment procedure performed in a twin gestation complicated by a
      large fetal neck mass. CASE: A giant fetal cervical mass was diagnosed in one
      fetus of a 20-week twin gestation by sonography and magnetic resonance imaging.
      At 35 weeks' gestation, the ex utero intrapartum treatment procedure was
      performed successfully for delivery of the normal twin, followed by intrapartum
      airway access of the twin with the neck mass. CONCLUSION: Even in twin
      gestations, the ex utero intrapartum treatment procedure is the delivery method
      of choice for fetuses with giant neck masses.

PMID- 10912409
TI  - Prenatal sonographic diagnosis of uterine rupture following open fetal surgery.
AB  - BACKGROUND: Reported cases of uterine rupture diagnosed by ultrasound have shown
      fetal membranes ballooning through uterine rupture sites, or adjacent areas of
      hemorrhage. CASE: A 27-year-old gravida 3, para 2 had open fetal surgery to
      repair a fetal myelomeningocele at 28 weeks' gestation. Her postoperative course
      was complicated by threatened preterm labor and anhydramnios. At 33 weeks'
      gestation, with maternal symptoms of bowel obstruction, ultrasound showed a fetal
      leg and section of umbilical cord protruding through the uterine wall.
      CONCLUSION: Even in the presence of anhydramnios, uterine wall rupture was
      identified, because ultrasound evaluation of the uterine wall showed prolapsed
      fetal parts and umbilical cord. Persistent anhydramnios after open fetal surgery
      should prompt a search for uterine rupture.

PMID- 10912411
TI  - Modified cesarean hysterectomy for placenta previa percreta with bladder
      invasion: retrovesical lower uterine segment bypass.
AB  - BACKGROUND: Present conservative and radical surgical management of placenta
      previa percreta with bladder invasion is associated with significant hemorrhage
      and the need for blood salvage, transfusion, and component therapy. Conventional
      cesarean hysterectomy strategies have high surgical morbidity, despite adequate
      personnel and resources. CASE: A 37-year-old, gravida 3, para 2-0-0-2, with a
      radiographic diagnosis of placenta previa percreta with bladder invasion, and
      confirmed fetal lung maturity, had a modified cesarean hysterectomy at 34 weeks'
      gestation. The bladder was partially mobilized beneath the percreta invasion site
      via the paravesical spaces. Estimated blood loss was 900 mL. Superficial
      placental bladder invasion was confirmed by pathology. The postoperative course
      was uneventful. CONCLUSION: Modified cesarean hysterectomy prevented hemorrhage
      and need for blood salvage, transfusion, or component therapy in managing a case
      of placenta previa percreta with bladder invasion.

PMID- 10912410
TI  - Umbilical artery regression: a rare complication of intravascular fetal
      transfusion.
AB  - BACKGROUND: Intravascular fetal transfusion is an important therapeutic advance
      but is associated with several complications. Regression of an umbilical artery
      associated with transfusion is rare. CASE: A case of red blood cell
      alloimmunization managed by serial transfusions was complicated by functional
      loss of an umbilical artery during pregnancy. Refractory fetal bradycardia
      occurred during the last transfusion procedure, requiring emergency preterm
      cesarean delivery. Coagulative necrosis, thrombosis, and focal calcification of
      one umbilical artery was confirmed after delivery. CONCLUSION: Umbilical artery
      regression associated with transfusion therapy is rare and may complicate
      subsequent fetal transfusions.

PMID- 10912412
TI  - Neonatal Hirschsprung disease, dysautonomia, and central hypoventilation.
AB  - BACKGROUND: A reported association between congenital central hypoventilation,
      long-segment intestinal aganglionosis (Hirschsprung disease), and autonomic
      dysfunction, with a high recurrence risk and mortality rate, is associated with
      abnormal neural crest development (neurocristopathy). CASE: A fetus had
      increasing polyhydramnios, no stomach bubble, and repeatedly nonreactive fetal
      heart rate tracings despite normal activity. There were no other fetal anomalies
      on ultrasound. Postnatally all of the above clinical features were diagnosed,
      prompting diagnosis of neurocristopathy syndrome. She died at 2 weeks of age.
      CONCLUSION: Antenatal polyhydramnios, nonreactive nonstress tests, and absent
      stomach bubble in an active fetus indicated neurocristopathy.

PMID- 10912413
TI  - Genital piercing to enhance sexual satisfaction.

PMID- 10912415
TI  - Menstrual abnormalities in a premenopausal woman with endometrial malacoplakia.

PMID- 10912414
TI  - Residual endometrium after uterine balloon ablation.

PMID- 10912416
TI  - Pyometra associated with retained products of conception.

PMID- 10912417
TI  - Anaphylactoid reaction after cryotherapy of the cervix.

PMID- 10912418
TI  - Cutaneous metastases of endometrial adenocarcinoma with squamous cell
      differentiation.

PMID- 10912419
TI  - Joint endoprosthesis lymphadenopathy mimicking lymph node involvement in a
      patient with endometrial carcinoma.

PMID- 10912420
TI  - Solitary brain metastasis indicating recurrent primary peritoneal carcinoma.

PMID- 10912421
TI  - Placenta increta complicating first-trimester D&C.

PMID- 10912422
TI  - Placenta increta presenting as delayed postabortal hemorrhage.

PMID- 10912423
TI  - Fluvastatin exposure during pregnancy.

PMID- 10912424
TI  - Successful pregnancy in an acromegalic women treated with octreotide.

PMID- 10912425
TI  - Laparoscopic treatment of uterine prolapse during pregnancy.

PMID- 10912426
TI  - Endometriosis of the appendix with symptoms of acute appendicitis in pregnancy.

PMID- 10912427
TI  - Gastric outlet obstruction at 30 weeks' gestation.

PMID- 10912428
TI  - Non-Hodgkin's lymphoma presenting with gigantomastia in pregnancy.

PMID- 10912429
TI  - Pregnancy with mitochondrial encephalopathy, lactic acidosis, and strokelike
      episodes syndrome.

PMID- 10912430
TI  - Ultrasound diagnosis of nuchal cord: the gray-scale divot sign.

PMID- 10912431
TI  - Fetomaternal hemorrhage in two pregnancies without prior risk factors.

PMID- 10912432
TI  - Sacrococcygeal teratoma with vascular placental dissemination.

PMID- 10912433
TI  - Neonatal brain abscess: complication of fetal monitoring.

PMID- 10912434
TI  - Pharmacokinetics during pregnancy: evidence-based maternal dose formulation.
AB  - OBJECTIVE: To review the literature regarding how drug pharmacokinetics differ
      between pregnant and nongravid women. DATA SOURCES: Articles published between
      1963 and 1997 were retrieved from the database of the National Library of
      Medicine for review, using the key words "pregnancy," "pharmacokinetics," and
      "human." Additional articles and book chapters were identified from the
      bibliographies of articles retrieved. METHODS OF STUDY SELECTION: Articles had to
      include primary data that were not previously published. Data abstracted from
      articles meeting the inclusion criteria included: sample size, estimated
      gestational age, area under the curve, volume of distribution, maximum plasma
      concentration, steady-state concentration, half-life, time to maximum plasma
      concentration, clearance, and data from nonpregnant controls. TABULATION,
      INTEGRATION, AND RESULTS: Of more than 1000 articles published, 61 articles and
      book chapters reported relevant pharmacokinetic data, such as those listed, based
      on primary data. Only two studies synthesized pharmacokinetic data into
      guidelines for individualized clinical regimens. CONCLUSION: Available data
      regarding the pharmacokinetics of therapeutic regimens during pregnancy do not
      provide clinically relevant guidelines for the formulation of therapy for
      individual patients. Pharmacokinetic investigations during pregnancy that produce
      evidence-based guidelines for treating individual patients were identified as a
      major area of need. Minimum requirements are recommended for reporting
      pharmacokinetic studies in obstetrics.

PMID- 10912435
TI  - The second-trimester fetus with isolated choroid plexus cysts: a meta-analysis of
      risk of trisomies 18 and 21.
AB  - OBJECTIVE: To assess the risk of trisomy 18 and trisomy 21 associated with
      isolated choroid plexus cysts diagnosed by ultrasound in the second trimester.
      METHODS OF STUDY SELECTION: We reviewed the unabridged PREMEDLINE and MEDLINE
      databases for articles written in the English language regarding second-trimester
      fetal isolated choroid plexus cysts and trisomies 18 and 21, published in the
      period 1987-1997. Selection criteria included only second-trimester, prospective
      studies in which the rate of fetal isolated choroid plexus cysts could be
      calculated, the number of fetuses with trisomy 18 and 21 was reported clearly,
      and pregnant women of all ages were included, rather than only those at high risk
      for aneuploidy due to advanced maternal age. TABULATION AND RESULTS: Thirteen
      prospective studies, comprising 246,545 second-trimester scans, were selected.
      Among 1346 fetuses with isolated choroid plexus cysts, seven had trisomy 18, and
      five had trisomy 21. For each study, a 2 x 2 table was constructed and the
      likelihood ratio of a positive test was computed. The likelihood ratios for
      trisomies 18 and 21 were found to be homogeneous (P = .08 for trisomy 18, and P =
      .16 for trisomy 21). The summary likelihood ratio and 95% confidence interval
      (CI) for each chromosomal abnormality were calculated using the Mantel-Haenszel
      fixed effects model of meta-analysis. The summary likelihood ratio for trisomy 18
      was 13.8 (CI 7.72, 25.14, P < .001) and for trisomy 21 was 1.87 (CI 0.78, 4.46, P
      = .16). CONCLUSION: The likelihood of trisomy 18 was 13.8 times greater than the
      a priori risk in fetuses with isolated choroid plexus cysts diagnosed in the
      second trimester. However, the likelihood of trisomy 21 was not significantly
      greater than the a priori risk with isolated choroid plexus cysts. The data
      supported offering pregnant women karyotyping to rule out trisomy 18 when
      maternal age at delivery is 36 years or older, or when the risk for trisomy 18
      detected by serum multiple-marker screen is more than one in 3000.

PMID- 10912436
TI  - Statistical evidence about the mechanism of action of the Yuzpe regimen of
      emergency contraception.
AB  - OBJECTIVE: To determine whether published statistical evidence about the
      effectiveness of the Yuzpe regimen of emergency contraception provides insight
      about its mechanism of action. DATA SOURCES: We searched the literature for
      studies that present information on the effectiveness of the Yuzpe regimen, on
      the probability of conception by menstrual cycle day, or on the occurrence of
      ovulation in women treated with the regimen. Searches of the electronic databases
      MEDLINE, POPLINE, EMBASE, and BIOSIS were supplemented by scrutiny of the
      bibliographies of all papers identified through the electronic search. METHODS OF
      STUDY SELECTION: We identified a review of the effectiveness of the Yuzpe regimen
      based on all seven clinical trials that present the number of women treated on
      each cycle day and the outcome of each treatment; this review also provided
      external estimates of the probability of conception by cycle day of unprotected
      intercourse from two other clinical studies. We identified three clinical studies
      of ovulation after treatment with the Yuzpe regimen. We included all identified
      studies in our analysis. TABULATION, INTEGRATION, AND RESULTS: We compared 40
      estimates of the actual effectiveness of the Yuzpe regimen with the maximum
      theoretical effectiveness that could be obtained if the regimen worked only by
      preventing or delaying ovulation. In the overwhelming majority of these
      comparisons, the former exceeded the latter. CONCLUSION: The Yuzpe regimen could
      not be as effective as it appears to be if it worked only by preventing or
      delaying ovulation.

PMID- 10912437
TI  - Vulvar vestibulitis: physical or psychosexual problem?
AB  - OBJECTIVE: To examine whether vestibulitis has a physical or a psychosexual
      etiology. DATA SOURCES: MEDLINE was searched to retrieve publications dating from
      January 1981 through June 1998 that evaluated the outcomes of surgical treatment
      and the psychosexual theory of the origin of vestibulitis. INTEGRATION: Articles
      were analyzed for methods of subject selection and surgery, surgical outcome, and
      length of follow-up. RESULTS: A significant decrease in symptoms (complete
      responses + partial responses) was reported by 89% of 646 women who had
      perineoplasty for vulvar vestibulitis. Complete resolution of dyspareunia with
      surgical treatment was reported in 72% of 512 women whose cases were reviewed in
      studies in which complete responses and partial responses were evaluated
      separately. Women with vestibulitis did not differ from the normal population
      with respect to marital satisfaction, psychologic distress, or psychopathology. A
      suggestion that childhood sexual abuse caused vestibulitis has not been
      confirmed. The findings of somatization and shyness might be explained as results
      rather than causes of vulvar vestibulitis. CONCLUSION: We do not agree that
      vestibulitis is a psychosexual problem and one that should not be treated
      surgically. A high rate of success can be achieved with proper surgical
      treatment.

PMID- 10912438
TI  - Hormone replacement therapy and the risk of colorectal cancer: a meta-analysis.
AB  - OBJECTIVE: To review systematically the association between hormone replacement
      therapy (HRT) and the risk of developing or dying from colorectal cancer. DATA
      SOURCES: We searched the English-language literature using MEDLINE, Current
      Contents, CancerLit, and bibliographies of selected studies. METHODS OF STUDY
      SELECTION: We included studies that specifically addressed the association of HRT
      with colorectal cancer, had adequate controls, and had retrievable risk
      estimates. We excluded letters, reviews, and multiple publications of the same
      data. TABULATION, INTEGRATION, AND RESULTS: Studies were evaluated independently
      by two of the authors. The exposures of interest were ever, recent, or former use
      of HRT, and the main outcome measures were colon and rectal cancer incidence and
      mortality. To reduce the risk of a "healthy estrogen user" bias, we defined
      recent HRT use as either at time of assessment or within the previous year. The
      most adjusted risk estimates were extracted. We used a random-effects model to
      calculate summary relative risks (RRs) and confidence intervals (CIs). Recent use
      of HRT was associated with a 33% reduction in the risk of colon cancer (RR =
      0.67; 95% CI 0.59, 0.77). Protection was limited to recent users; the risk of
      colon cancer with ever use of HRT was 0.92 (95% CI 0.79, 1.08). Duration of use
      was not significant. Three studies addressed the risk of fatal colon cancer; the
      summary RR for death from colon cancer in HRT users was 0.72 (95% CI 0.64, 0.81)
      compared with nonusers. Rectal cancer incidence was not associated with HRT.
      CONCLUSION: The risk of colon cancer may be decreased among recent postmenopausal
      HRT users. Although data are limited, the risk of fatal colon cancer also may be
      lower in HRT users.

PMID- 10912439
TI  - Haematocrit and plasma viscosity in atrial fibrillation.

PMID- 10912440
TI  - Anti-arrhythmic properties of moxonidine--implications for the MOXCON study.

PMID- 10912441
TI  - Left posterior fascicular ventricular tachycardia in myotonic dystrophy.

PMID- 10912442
TI  - Ruptured aneurysm of sinus of valsalva with ventricular septal defect: the role
      of transesophageal echocardiography in diagnosis.
AB  - We present a case of ruptured aneurysm of sinus of valsalva (ASV) along with
      subaortic ventricular septal defect (VSD). Transesophageal echocardiographic
      examination in addition to transthoracic echocardiography provides more powerful
      information about ASVs and coexistent cardiac malformations. This may be
      additional value for the cardiac surgeon planning resection of the lesion.

PMID- 10912443
TI  - Acute rheumatic carditis in Henoch-Schonlein purpura.

PMID- 10912444
TI  - Catheter ablation for tachyarrhythmia-induced cardiomyopathy in infants.

PMID- 10912445
TI  - Reexpression of T-type Ca channels after myocardial infarction: does it play a
      role in cardiac excitation?

PMID- 10912446
TI  - The 'second factor' of tachycardia-induced atrial remodeling.

PMID- 10912447
TI  - Cardiac microdialysis a powerful tool.

PMID- 10912448
TI  - EDHF and residual NO: different factors.

PMID- 10912449
TI  - Progress in the understanding of cardiac early afterdepolarizations and torsades
      de pointes: time to revise current concepts.

PMID- 10912451
TI  - Endogenous factors involved in regulation of tone of arterial vasa vasorum:
      implications for conduit vessel physiology.
AB  - The walls of conduit blood vessels are nourished by diffusion of oxygen from
      luminal blood and from the vasa vasorum. The vasa vasorum, or 'vessels of a
      vessel', form a network of microvessels that lie in the adventitia and penetrate
      the outer media of the host vessel wall. Although the importance of the vasa
      vasorum in providing nutritional support is not well defined, obstruction of
      blood flow through these vessels has been implicated in the pathogenesis of
      certain cardiovascular diseases including atherosclerosis. This review focuses on
      the mechanisms that regulate tone in the vasa vasorum of large arteries and the
      functional implications of changes in reactivity of vasa vasorum.

PMID- 10912450
TI  - The role of taurine in the pathogenesis of the cardiomyopathy of insulin
      dependent diabetes mellitus.
AB  - The cellular and molecular physiology and pathology of insulin-dependent diabetes
      mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly
      studied and understood through the use of animal models. Fundamental differences
      between the IDDM and NIDDM animal models may help to explain the etiology behind
      diabetic cardiomyopathy, one of the most severe complications of IDDM.
      Experimental rat models of IDDM exhibit a characteristic increase in tissue
      levels of taurine in the heart, a change that is not seen in NIDDM rats. This
      article deals with the causes and possible consequences of this observation which
      may contribute to the development of diabetic cardiomyopathy. Modulation of
      pyruvate dehydrogenase (lipoamide) (PDH; EC 1.2.4.1) activity was found to be a
      possible mode for taurine involvement. PDH is a mitochondrial protein and is the
      rate-limiting step in the generation of acetyl CoA from glycolysis. In IDDM, PDH
      activity is decreased through a mechanism that includes the stimulation of the de
      novo synthesis of a kinase activator protein (KAP) which phosphorylates PDH and
      inactivates the enzyme. This lesion does not occur in NIDDM rat hearts. Taurine
      is known to inhibit the phosphorylation of PDH in vitro, and in taurine-depleted
      rats PDH phosphorylation is known to increase. Thus, the increased levels of
      taurine in the diabetic heart may be inhibiting this phosphorylation which in
      turn may be stimulating the synthesis of KAP through a negative feedback process.
      The main argument for this theory would be the lack of change in both the taurine
      levels and the activity of PDH in the NIDDM rat model.

PMID- 10912452
TI  - L-Arginine administration prevents reperfusion-induced cardiomyocyte
      hypercontracture and reduces infarct size in the pig.
AB  - OBJECTIVE: Stimulation of cGMP synthesis protects cardiomyocytes against
      reoxygenation-induced hypercontracture. The purpose of this study was to
      determine whether L-arginine supplementation has a protective effect against
      reperfusion-induced hypercontracture and necrosis in the intact animal. METHODS:
      Twenty-four Large-White pigs were randomized to receive either 100 mg/kg of L
      arginine i.v. or vehicle 10 min before 48 min of coronary occlusion and 2 h of
      reperfusion. Hemodynamic variables, coronary blood flow and myocardial segment
      length changes (piezoelectric crystals) were monitored. Postmortem studies
      included quantification of myocardium at risk (in vivo fluorescein), infarct size
      (triphenyltetrazolium reaction), myocardial myeloperoxidase activity and
      histological analysis. Systemic, coronary vein, and myocardial cGMP concentration
      were measured in additional animals. RESULTS: Administration of L-arginine had no
      significant effect in hemodynamics or coronary blood flow. During reperfusion,
      myocardial cGMP content was reduced in the LAD as compared to control myocardium
      (P=0.02). L-Arginine increased myocardial cGMP content and caused a transient
      increase in plasma cGMP concentration during the initial minutes of reperfusion
      (P=0.02). The reduction in end-diastolic segment length induced by reperfusion,
      reflecting hypercontracture, was less pronounced in the L-arginine group
      (P=0.02). Infarct size was smaller in pigs receiving L-arginine (47.9+/-7.2% of
      the area at risk) than in controls (62.9+/-4.9%, P=0.047). There were no
      differences between groups in leukocyte accumulation in reperfused myocardium
      (P=0.80). CONCLUSION: L-Arginine supplementation reduces myocardial necrosis
      secondary to in situ ischemia-reperfusion by a direct protective effect against
      myocyte hypercontracture.

PMID- 10912453
TI  - Local neurohumoral regulation in the transition to isolated diastolic heart
      failure in hypertensive heart disease: absence of AT1 receptor downregulation and
      'overdrive' of the endothelin system.
AB  - OBJECTIVE: Although isolated diastolic heart failure with preserved left
      ventricular (LV) systolic function frequently occurs, regulation of local
      neurohumoral factors in the transition from diastolic dysfunction without signs
      of heart failure to diastolic failure, a target for therapeutic strategy, remains
      to be clarified, partly because of a lack of animal models. Our laboratory
      recently demonstrated that Dahl-Iwai salt-sensitive (Dahl-S) rats fed on a high
      salt diet since 7 weeks of age develop hypertension followed by compensated LV
      hypertrophy at 13 weeks and transition to isolated diastolic heart failure at 19
      weeks. METHODS: Gene expression of the components of the renin-angiotensin
      system, endothelin (ET) system and natriuretic peptide system in the left
      ventricle was investigated in the transition to isolated diastolic heart failure
      in this model. RESULTS: The compensated ventricular hypertrophy was associated
      with slight increases in angiotensin-converting enzyme (ACE) and angiotensin II
      type-1a (AT1a) receptor mRNA levels. Although preproET-1 (ppET-1) and ET
      converting enzyme-1 (ECE-1) mRNA levels were not increased, mRNA levels of ET
      type-A (ETA) and ET type-B (ETB) receptors were increased. Atrial natriuretic
      peptide (ANP) mRNA level increased, but not brain natriuretic peptide (BNP) mRNA
      level. At the decompensated failing stage (at 19 weeks), ACE mRNA level further
      increased without downregulation of ATla receptor mRNA level. The mRNA levels of
      ppET-1 and ECE-1 increased with persistent upregulation of mRNA levels of ETA and
      ETB receptors, and immunohistochemical staining for ET-1 was found at endothelial
      cells and myocytes. BNP mRNA level increased with a further increase in ANP mRNA
      level. CONCLUSIONS: The transition to isolated diastolic heart failure in
      hypertrophied hearts was associated with preserved gene expression of the renin
      angiotensin system and 'overdrive' of gene expression of the ET system. BNP gene
      expression is likely to be activated by the progression of diastolic failure
      rather than by LV hypertrophy alone.

PMID- 10912454
TI  - Characterisation of the transient outward K+ current in rabbit sinoatrial node
      cells.
AB  - OBJECTIVE: To (i) characterise the electrophysiological and pharmacological
      properties of the transient outward K+ current, I(to), (ii) determine the
      relationship between the density of I(to) and cell size, and (iii) determine the
      role of I(to) in electrical activity in rabbit sinoatrial node cells at 35
      degrees C. METHODS: Rabbit sinoatrial node cells were studied using whole-cell
      voltage and current clamp techniques. RESULTS: I(to) showed half activation and
      inactivation at +11 and -49 mV, respectively. I(to) was blocked by 4
      aminopyridine (4-AP) as well as the class I agents, quinidine and flecainide,
      with EC50 values of 326, 21 and 19 microM, respectively. The densities of the
      transient and sustained components of 4-AP-sensitive current were significantly
      correlated with cell capacitance, a measure of cell size, and were greater in
      cells with a larger capacitance. Block of I(to) by 4-AP affected both the action
      potential and pacemaker activity of sinoatrial node cells and the effects were
      greater in cells with a larger capacitance. CONCLUSIONS: I(to) in sinoatrial node
      cells shows similar electrophysiological and pharmacological properties to I(to)
      in atrial and ventricular cells. The expression of I(to) in sinoatrial node cells
      is heterogeneous and differs in large and small cells (likely to be from the
      periphery and centre of the sinoatrial node, respectively). I(to) plays an
      important role in action potential configuration and pacemaker activity in
      sinoatrial node cells, especially in larger cells.

PMID- 10912455
TI  - Reexpression of T-type Ca2+ channel gene and current in post-infarction remodeled
      rat left ventricle.
AB  - OBJECTIVE: T-type Ca2+ currents (I(Ca-T)) are present in neonatal rat myocytes
      but is not detected in adult ventricular myocytes. The present study was designed
      to investigate the expression of the T-type Ca2+ channel gene and current in post
      infarction remodeled hypertrophied rat left ventricle (LV). METHODS: We compared
      the expression of T-type Ca2+ channel gene alpha-1G in neonatal rat LV, in adult
      sham-operated LV and remodeled hypertrophied LV 3 to 4 weeks post-myocardial
      infarction (MI) using RNase protection assay (RPA). The cDNA fragment of alpha-1G
      used in RPA was obtained from poorly conserved region of recently published T
      type Ca2+ channel coding sequence of rat by RT-PCR. The fragment was verified by
      restriction enzyme digestion and sequencing. The presence of I(Ca-T) in LV of
      sham and post-MI rats was examined using patch-clamp techniques. In the presence
      of K+-free, Na+-free external solution, I(Ca-T) was separated from I(Ca-L) by
      different holding potentials (HP). I(Ca-T) was also recorded during
      depolarization to -40 mV from a HP of -80 mV with NaCl in external solution and
      I(Na) suppressed by 100 microM tetrodotoxin (TTX). RESULTS: The T-type Ca2+
      channel gene alpha-1G was expressed in neonatal heart, the expression level
      decreased by 80%, in adult sham heart and was reexpressed in MI (158% increases
      compared to sham; P<0.01). I(Ca-T) was recorded in 11 of 31 MI cells in presence
      of K+-free, Na+-free external solution and in 9 of 14 cells when I(Na) was
      suppressed by TTX. I(Ca-T) was not detected in any of 21 sham cells. I(Ca-T)
      density was 1.1+/-0.4 pA/pF. I(Ca-T) was more sensitive to Ni2+ and less
      sensitive to nisoldipine. CONCLUSIONS: T-type Ca2+ channel gene and current are
      reexpressed in rat post-MI remodeled LV myocytes. Its functional significance in
      the post-MI remodeling process remains to be defined.

PMID- 10912456
TI  - Stimulus interval-dependent differences in Ca2+ transients and contractile
      responses of diabetic rat cardiomyocytes.
AB  - OBJECTIVE: The aim of this study was to gain further insights into the
      consequences of insulin-dependent diabetes mellitus on cardiomyocyte calcium
      handling. METHODS: The effects of steady state and transient changes in stimulus
      frequency on the intracellular Ca2+ transient and cell shortening were examined
      in left ventricular cardiomyocytes isolated from the hearts of control and
      streptozotocin-induced diabetic rats. RESULTS: During steady state stimulation
      diabetic rat cardiomyocytes displayed a slower decay of the Ca2+ transient and
      longer times for maximum cell shortening and re-lengthening. At 1.5 mM
      extracellular [Ca2+], increasing stimulus frequency over the range 0.2-1.0 Hz led
      to an increase in resting and peak [Ca2+]i as well as the amplitude of the
      transient in both the control and diabetic groups. At frequencies greater than
      0.4 Hz the amplitude of the transient was significantly depressed in diabetic rat
      cells and this was not normalized by increasing extracellular [Ca2+] to 2.5 mM.
      Recovery of sarcoplasmic reticulum (SR) Ca2+ release was measured from the time
      course of restitution of the intracellular Ca2+ transient. In both control and
      diabetic rat cardiomyocytes recovery of the transient occurred in two phases. In
      diabetic rat myocytes, the initial rapid phase of restitution at intervals <1 s
      was markedly slowed. The fraction of Ca2+ recirculating between the SR and the
      cytosol was estimated from the decline in amplitude of transients following post
      rest potentiation. There was no difference in this fraction between control and
      diabetic rat cells either at 1.5 or 2.5 mM extracellular [Ca2+]. CONCLUSION: The
      blunted frequency response of diabetic rat cardiomyocytes at frequencies greater
      than 0.4 Hz is consistent with reduced SR Ca2+ uptake leading to reduced SR Ca2+
      content and subsequent release. At stimulus intervals greater than 1 Hz this is
      likely to be exacerbated by slower recovery of SR Ca2+ release. Despite the
      evidence for depressed SR Ca2+ uptake, the relative amount of Ca2+ recirculating
      within diabetic rat cardiomyocytes remains unaltered. This is most likely due to
      an accompanying reduction in Ca2+ efflux from the cell due either to depressed
      Na+/Ca2+ exchanger activity, or an elevation in intracellular Na+ levels.

PMID- 10912457
TI  - Angiotensin II directly increases transforming growth factor beta1 and
      osteopontin and indirectly affects collagen mRNA expression in the human heart.
AB  - OBJECTIVES: Angiotensin II (Ang II) induces fibroblast proliferation and collagen
      synthesis in the myocardium, but its precise mechanisms of action in human hearts
      are still unknown. Therefore, we investigated whether Ang II directly affects the
      collagen mRNA content in the human myocardium and in isolated human cardiac
      fibroblasts or whether the growth factors TGFbeta-1 and osteopontin are involved
      in this process. METHODS AND RESULTS I: In a first set of experiments, the direct
      effect of Ang II on collagen I, TGFbeta-1 and osteopontin mRNA content in fresh
      samples of human atrial myocardium was determined by the use of a short
      stimulation period. After 4 h, Ang II-stimulated atrial samples gave a
      significantly higher expression of both TGFbeta-1 (183+/-21% of control, p<0.05)
      and osteopontin mRNA (275+/-58%, p<0.02) than the controls. In contrast, the
      expression of collagen I mRNA was unchanged (95+/-8%). Stimulation with TGFbeta-1
      led to an increase in collagen I and III mRNA (127+/-10%, p<0.05; 140+/-15%,
      p<0.02). METHODS AND RESULTS II: In a second protocol, to assess the effects of
      longer stimulation periods, we determined the effects of Ang II and its potential
      mediator TGFbeta-1 on collagen I, III and fibronectin mRNA expression and on
      proliferation of cultured human cardiac fibroblasts. Ang II caused a dose
      dependent stimulation of proliferation but did not affect collagen I, II or
      fibronectin mRNA content after 24 h. In contrast, TGFbeta-1 stimulation
      significantly increased collagen I and III mRNA expression (124+/-5% and 128+/
      5%, p<0.002). CONCLUSIONS: In the human heart, Ang II does not directly increase
      collagen or fibronectin mRNA, but it does increase TGFbeta-1 and osteopontin mRNA
      expression. Since TGFbeta-1 induces collagen I and III mRNA in atrial samples and
      in isolated cardiac fibroblasts, it may represent a necessary mediator of the Ang
      II effects in the human heart.

PMID- 10912458
TI  - Gap junctional remodeling in relation to stabilization of atrial fibrillation in
      the goat.
AB  - OBJECTIVE: It has been postulated that high atrial rate induced changes at the
      level of the gap junctions ('gap junctional remodeling', i.e. changes in
      distribution, intercellular orientation and expression of gap junction proteins),
      could be part of the vicious circle of electrophysiologic and structural changes
      leading to sustained atrial fibrillation (AF). To obtain experimental evidence in
      favour of such a postulate the timing of this remodeling process was studied in
      relation to the development of sustained AF in a goat model. METHODS AND RESULTS:
      Thin sections from the left (LAA) and right atrial appendage (RAA) from goats in
      sinus rhythm (SR) or AF, induced through programmed endocardial burst pacing for
      time periods between 0 and 16 weeks, were immunolabeled with antibodies against
      connexin(Cx)40 and Cx43 and analysed by immunofluorescence and confocal laser
      scanning microscopy. During SR the distribution pattern for Cx43 was completely
      homogeneous (LAA and RAA) and for Cx40 mostly homogeneous (LAA: all five goats,
      RAA: three out of five goats). The distribution pattern for Cx43 remained stable
      during AF, while the Cx40 distribution pattern became increasingly heterogeneous,
      both in the LAA and RAA, with increasing duration of pacing. This increase in
      heterogeneity in Cx40 distribution correlated (Spearman rank order) with an
      increase in stability of AF and the occurrence of structural changes (myolysis)
      in atrial myocytes. The Cx40/Cx43 immunofluorescence signal ratio in both the LAA
      and RAA appeared to be significantly lower in AF (1-16 weeks) as compared to SR
      (0 weeks); going from 0 to 16 weeks average ratios decreased 54.5% (n=5; P=0.026)
      in the LAA and 35.8 (n=5; P=0.034) in the RAA. Western blot analyses revealed
      similar decreases in the total Cx40/Cx43 protein ratio, on average 50.0% (n=5;
      P=0.008) and 47.8% (n=5; P=0.02) in the LAA and RAA, respectively. No changes
      were measured in the levels of Cx40 or Cx43 mRNA, as was assessed through RT-PCR.
      CONCLUSION: The time course of changes in the distribution and content of Cx40
      gap junctions as observed during endocardial burst pacing of the goat atrium
      suggests that Cx40 gap junctional remodeling might be involved in the
      pathogenesis of sustained atrial fibrillation.

PMID- 10912459
TI  - Effect of protein kinase A on calcium sensitivity of force and its sarcomere
      length dependence in human cardiomyocytes.
AB  - OBJECTIVE: We investigated whether the Frank-Starling mechanism is absent or
      preserved in end-stage failing human myocardium and if phosphorylation of
      contractile proteins modulates its magnitude through the sarcomere length
      dependence of calcium sensitivity of isometric force development. METHODS: The
      effect of phosphorylation of troponin I and C-protein by the catalytic subunit of
      protein kinase A (3 microg/ml; 40 min at 20 degrees C) was studied in single
      Triton-skinned human cardiomyocytes isolated from donor and end-stage failing
      left ventricular myocardium at sarcomere lengths measured at rest of 1.8, 2.0 and
      2.2 microm. Isometric force development was studied at various free-calcium
      concentrations before and after protein kinase A incubation at 15 degrees C (pH
      7.1). RESULTS: Maximal isometric tension at 2.2 microm amounted to 39.6+/-10.4
      and 33.7+/-3.5 kN/m2 in donor and end-stage failing cardiomyocytes, respectively.
      The midpoints of the calcium sensitivity curves (pCa50) of donor and end-stage
      failing hearts differed markedly at all sarcomere lengths (mean delta
      pCa50=0.22). A reduction in sarcomere length from 2.2 to 1.8 microm caused
      reductions in maximum isometric force to 64% and 65% and in pCa50 by 0.10 and
      0.08 pCa units in donor and failing cardiomyocytes, respectively. In donor
      tissue, the effect of protein kinase A treatment was rather small, while in end
      stage failing myocardium it was much larger (delta pCa50=0.24) irrespective of
      sarcomere length. CONCLUSIONS: The data obtained indicate that the Frank-Starling
      mechanism is preserved in end-stage failing myocardium and suggest that sarcomere
      length dependence of calcium sensitivity and the effects of phosphorylation of
      troponin I and C-protein are independent.

PMID- 10912460
TI  - Electrical conductance of mouse connexin45 gap junction channels is modulated by
      phosphorylation.
AB  - In this study we report about the modulation of connexin45 (Cx45) gap junction
      channel properties by phosphorylation of the connexin molecules through different
      protein kinases. Phosphorylation of Cx45 was studied in HeLa cells transfected
      with mouse Cx45 (mCx45). Using Western blotting (WB) and immunocytochemistry,
      these cells were found exclusively positive for Cx45 and the protein was
      separated as a doublet of bands with a calculated mass of 46 and 48 kD. After
      dephosphorylation using calf intestine phosphatase (CIP), the 48 kD band
      disappeared almost completely leaving a single band at 46 kD. This effect can be
      prevented by including phosphatase inhibitors during CIP treatment. These results
      indicate that the 48 kD signal represents a phosphorylated form of Cx45. To
      investigate the effects of (de)phosphorylation of Cx45 on the conductive
      properties of gap junction channels built of this connexin, cell pairs were
      subjected to dual voltage clamp experiments and coupling was determined before
      and after addition of PMA, 4alpha-PDD, cAMP, cGMP, and pervanadate to the
      superfusate. 100 nM of the PKC activating phorbol ester PMA increased normalized
      junctional conductance by 50.9+/-28%. 100 nM of the inactive phorbol ester 4alpha
      PDD had no significant effect. Activation of PKA with 1 mM 8-Br-cAMP decreased
      coupling by 20.9+/-5.7% while 1 mM 8-Br-cGMP (PKG-activation) was ineffective.
      100 microM pervanadate, a tyrosine phosphatase inhibitor, reduced coupling by
      43.7+/-11.1%. Single channel measurements, under identical phosphorylating
      conditions, were not significantly different from each other and all frequency
      histograms exhibited two conductance peaks at approximately 20 and 40 pS. WB
      analysis revealed, as compared to control conditions, a relative increase of the
      48 kD signal upon stimulation with pervanadate (142+/-42%) and 8-Br-cAMP (50+/
      23%) whereas neither stimulation with PMA nor 8-Br-cGMP had a significant effect.
      These experiments show that electrical intercellular conductance via Cx45 gap
      junction channels is differentially regulated by phosphorylation. However,
      regulation does not act by changing single channel conductance, but most likely
      by modulation of the open probability of Cx45 gap junction channels.

PMID- 10912461
TI  - Characterization of the rat connexin40 promoter: two Sp1/Sp3 binding sites
      contribute to transcriptional activation.
AB  - OBJECTIVES: The gap junction protein connexin40 (Cx40) is differentially
      expressed during embryonic development and in adult tissues, for which the
      molecular basis is unknown. In order to elucidate the molecular mechanisms
      controlling Cx40 expression, we set out to map and characterize its promoter.
      METHODS: The transcriptional activity of individual rat Cx40 (rCx40)-derived
      promoter fragments fused to the luciferase reporter gene was determined by
      transfection/reporter assays in Cx40-expressing (A7r5, rat smooth muscle
      embryonic thoracic aorta cells, and BWEM, v-myc transformed rat fetal
      cardiomyocytes) and Cx40-nonexpressing cells (N2A, mouse neuroblastoma cells).
      The nature of DNA-protein interactions was investigated by a combination of
      standard electrophoretic-mobility-shift assays (EMSA) and EMSA/antibody
      supershift assays. RESULTS: Quantification of luciferase activity in cell lysates
      revealed that a 235-base-pair fragment, in between map positions -150 and +85
      relative to the transcription initiation site, is able to provide for a
      significant level of transcription in both Cx40-expressing (A7r5, BWEM) and 
      nonexpressing (N2A) cells. These results indicate that this region contains the
      basal promoter but is not sufficient to completely determine the endogenous Cx40
      expression pattern within these cell types. In search for the responsible
      transcriptional regulatory element(s), additional segments of the (-150, +85)
      region were deleted and the remaining fragments were tested for transcriptional
      activity. These studies established that the regions in between map positions (
      96, -71) and (+58, +85) contribute to promoter activity. EMSA with these regions
      revealed that predominantly two DNA-protein complexes are formed upon incubation
      with either A7r5, BWEM or N2A nuclear extracts, which could be both inhibited by
      including excess oligonucleotide containing the Sp1 consensus binding site in the
      binding reaction. Purified recombinant human Sp1 provided also for a shift in the
      EMSA using these promoter regions as target fragments. When the DNA-protein
      complexes formed with nuclear extract were subsequently incubated with either an
      anti-Sp1 or an anti-Sp3 antibody clear supershifts in the EMSA were obtained,
      indicating Sp1 and Sp3 binding to both the (-98, -64) and (+53, +87) regions. The
      introduction of mutations within the core sequence of the putative Sp1/Sp3
      binding sites present in these regulatory elements reduced the level of
      transcriptional activity and abrogated Sp1/Sp3 binding to these sites.
      CONCLUSION: The results indicate that at least two Sp1/Sp3 binding sites in the
      rCx40 promoter contribute to the transcriptional activation of its gene in
      cultured cells.

PMID- 10912462
TI  - Effects of probucol on changes of antioxidant enzymes in adriamycin-induced
      cardiomyopathy in rats.
AB  - OBJECTIVE: The clinical usefulness of doxorubicin (adriamycin, ADR) is restricted
      by the risk of developing congestive heart failure. Probucol has been reported to
      completely prevent ADR cardiomyopathy without interfering with its antitumor
      effects. The current study investigated the effects of ADR and probucol on
      antioxidant enzyme gene expression during adriamycin-induced cardiomyopathy in a
      rat model. METHODS: The mRNA abundance by Northern and immunoreactive protein
      levels by Western blotting of myocardial antioxidant enzymes, glutathione
      peroxidase (GSHPx), manganese superoxide dismutase (MnSOD) and catalase (CAT)
      were examined in relation to the enzyme activities in hemodynamically assessed
      control and treated animals. RESULTS: At 3 weeks post-treatment duration, ADR
      caused heart failure which was prevented by probucol. MnSOD mRNA abundance as
      well as protein levels were depressed by ADR treatment by 45% and 20%,
      respectively, and this change was prevented by probucol. However, the mRNA and
      protein levels of GSHPx and CAT were not significantly changed by ADR or
      probucol. ADR had no effect on SOD activity but this enzyme activity was
      increased by probucol and probucol plus ADR. GSHPx enzyme activity was decreased
      and oxidative stress as indicated by TBARS was increased by ADR and these changes
      were also modulated by probucol. CONCLUSION: An increase in oxidative stress,
      GSHPx inactivation and MnSOD downregulation during ADR cardiomyopathy were
      prevented by probucol treatment.

PMID- 10912463
TI  - Adrenergic inhibition of endogenous acetylcholine release on postganglionic
      cardiac vagal nerve terminals.
AB  - OBJECTIVE: The aim was to examine the adrenergic modulation of endogenous
      acetylcholine (ACh) release from vagal nerve terminals in the in vivo heart.
      METHODS: Using dialysis technique in anesthetized cats, we investigated the
      influence of exogenous noradrenaline on dialysate ACh response. Dialysis probes
      were implanted in the left ventricular myocardium and perfused with Krebs
      Henseleit buffer containing eserine (10(-4) M) at 3 microl/min. Dialysate ACh
      concentration was measured as an index of ACh release from cardiac vagal nerve
      terminals. The dialysate ACh response to vagal nerve stimulation was examined
      before and after local administration of noradrenaline (10(-5) M) through
      dialysis probes. RESULTS: Noradrenaline significantly attenuated the dialysate
      ACh response to vagal nerve stimulation (10 Hz) from 9.5+/-1.8 to 5.4+/-1.2 nM
      (n=7). In the presence of the alpha-adrenergic antagonist phentolamine (10(-4)
      M), noradrenaline did not attenuate the dialysate ACh response (from 9.8+/-2.7 to
      9.4+/-2.8 nM, n=6). The N-type Ca2+ channel blocker omega-conotoxin GVIA (10(-5)
      M) significantly attenuated the dialysate ACh response from 9.6+/-1.2 to 4.5+/
      0.7 nM (n=8). In the presence of omega-conotoxin GVIA, noradrenaline did not
      attenuate the dialysate ACh response (from 3.8+/-1.4 to 3.5+/-1.3 nM, n=7).
      CONCLUSIONS: Our results suggest the presynaptic adrenergic inhibition of ACh
      release on postganglionic cardiac vagal nerve terminals. Adrenergic inhibition of
      Ca2+ influx through the N-type Ca2+ channels could play a predominant role in the
      decrease in ACh release.

PMID- 10912464
TI  - Endothelium-dependent relaxation of rat aorta and main pulmonary artery by the
      phytoestrogens genistein and daidzein.
AB  - OBJECTIVE: The dietary phytoestrogens genistein and daidzein have been shown to
      relax agonist-preconstricted arteries in vitro; the mechanisms of relaxation
      remain incompletely understood. This study aimed to determine whether the
      relaxation of phenylephrine (PE)-constricted rat aorta and main pulmonary artery
      by genistein and daidzein was endothelium-dependent. METHODS: Effects of
      endothelial-denudation, and pretreatment with with 100 microM L-N(G)
      nitroarginine methyl ester (L-NAME) and/or 10 microM indomethacin on relaxation
      of PE (1 microM)-preconstricted contractures by genistein (1-100 microM) and
      daidzein (3-100 microM) were assessed by measuring isometric force development by
      rat arterial rings. The effect of L-NAME on relaxation to 17beta-estradiol (10
      microM) was also measured in aorta. RESULTS AND CONCLUSIONS: Genistein and
      daidzein caused concentration-dependent relaxation of aorta rings preconstricted
      with PE (1 microM). The IC50 values were 5.7 microM (n=8, 95% confidence limits
      4.3-7.7 microM) and 36.7 microM (n=12, 95% confidence limits 25.7-44.1 microM),
      respectively. Removal of the endothelium and pretreatment with L-NAME (100
      microM) significantly inhibited relaxation at 3, 10 and 30 microM genistein and
      10 and 30 microM daidzein. The contracture evoked in rat aorta by depolarization
      with 75 mM K+ solution was similarly relaxed by genistein in a partially
      endothelium-dependent manner. 17Beta-estradiol (10 microM) caused a 48.7+/-5.0%
      (n=11) relaxation of the PE contracture, which was significantly reduced to
      25.1+/-5.3% (n=7) by L-NAME. Relaxations brought about by 17beta-estradiol,
      genistein, and daidzein were not significantly affected by the genomic estrogen
      receptor antagonist ICI 182,780 (10 microM). Similar endothelium-dependent
      effects of genistein were observed in the main pulmonary artery. The results show
      that the relaxation of these rat arteries by concentrations of genistein and
      daidzein which overlap those present in human plasma after ingestion of soybean
      containing meals is largely endothelium dependent.

PMID- 10912465
TI  - Endothelium-dependent hyperpolarization and relaxation resistance to N(G)-nitro-L
      arginine and indomethacin in coronary circulation.
AB  - OBJECTIVE: It is controversial whether endothelium-dependent relaxation
      resistance to inhibitors of nitric oxide (NO) and prostacyclin synthases is
      completely attributed to endothelium-derived hyperpolarizing factor (EDHF). This
      study examined NO release and K+ channels involved in endothelium-dependent
      relaxation and hyperpolarization resistance to N(G)-nitro-L-arginine (L-NNA) and
      indomethacin in coronary arteries with emphasis on the microarteries. METHODS: NO
      release, isometric force, and membrane potential of porcine coronary arteries
      were measured using a NO-specific electrode, wire myograph, and microelectrode,
      respectively. RESULTS: In large arteries pretreated with indomethacin, bradykinin
      (BK) evoked a rise in [NO] from 5.5+/-2.4 nM to 105.0+/-19.6 nM and
      hyperpolarization. L-NNA treatment significantly reduced the BK-stimulated rise
      in [NO] to 32.1+/-11.3 nM but did not affect the hyperpolarization. In the
      presence of indomethacin and L-NNA, U46619 contracted and depolarized (from -51+/
      3 mV to -30+/-4 mV) vascular smooth muscle in microarteries. The addition of BK
      produced dose-dependent relaxation (maximal: 70.2+/-5.7%) and repolarization
      (membrane potential: -50+/-4 mV). Oxyhemoglobin eliminated indomethacin and L-NNA
      resistance rise in [NO] but not relaxation (42.3+/-4.4%) and repolarization (
      40+/-2 mV) by BK. Tetraethylammonium, charybdotoxin, and iberiotoxin partially
      decreased the BK-induced responses. Apamin alone did not affect the relaxation by
      BK; however, in combination with charybdotoxin it almost completely abolished the
      BK-induced relaxation and hyperpolarization. CONCLUSIONS: In porcine coronary
      arteries, both EDHF and NO contribute to BK-induced relaxation resistance to
      indomethacin and L-NNA. Large conductance Ca2+-activated K+ channels (BK(Ca)) may
      play an important role in mediating the BK-induced responses and small
      conductance Ca2+-activated K+ channels might function as 'backup' mechanisms when
      BK(Ca) is curtailed.

PMID- 10912466
TI  - Role of Ca2+- and swelling-activated Cl- channels in alpha1-adrenoceptor-mediated
      tone in pressurized rabbit mesenteric arterioles.
AB  - BACKGROUND: Ca2+-activated (I(Cl(Ca))) and swelling-induced (I(Cl(swell))) Cl-
      channels have, respectively, been postulated to participate in the membrane
      depolarization and contraction mediated by activation of alpha1-adrenoceptors and
      vascular wall distension during pressurization. Their respective function in
      generating active force in pressurized arterioles during alpha1-adrenoceptor
      stimulation remains unsettled. OBJECTIVES: Experimental protocols were designed
      to: (1) assess the relative contribution of I(Cl(Ca)) to the pressure-dependence
      of lumen diameter of mesenteric arterioles at different states of activation of
      the alpha1-adrenoceptor, and (2) investigate the potential role of I(Cl(swell))
      in spontaneous and agonist-mediated myogenic reactivity. METHODS: Segments of
      endothelium-denuded rabbit mesenteric arterioles with a lumen diameter of
      approximately 70 microm were cannulated at both ends and studied under isobaric
      conditions at 36 degrees C. Steady-state lumen diameter at each pressure step
      investigated (0-100 mmHg, in 20-mmHg increments) was measured by a video
      microscopy edge-detection technique. RESULTS: Under control conditions, 23% of
      the arterioles developed nifedipine-sensitive spontaneous myogenic tone. In the
      presence of 1 mM tetraethylammonium chloride (TEA) to inhibit Ca2+-dependent K+
      channels, the alpha1-agonist phenylephrine (PE) contracted the vessels in a
      concentration-dependent manner (0.1-10 microM) and potentiated myogenic
      reactivity. The contraction mediated by 1 microM PE/TEA was abolished by 1 microM
      nifedipine, indicating that Ca2+ entry through voltage-gated Ca2+ channels was a
      necessary step in the cascade leading to contraction. Niflumic acid (NfA, 100
      microM), a relatively selective inhibitor of I(Cl(Ca)), had no effect on myogenic
      tone but reversed the PE-induced contraction, varying with the concentration of
      PE and transmural pressure. For PE concentrations between 0.1 and 1 microM, but
      not for 10 microM PE, the relaxing efficacy of NfA decreased as applied pressure
      was raised from 0 to 100 mmHg. At all pressure steps, the NfA-induced relaxation
      was inversely related to the concentration of PE. DIDS (200 microM), another Cl-
      channel blocker, inhibited spontaneous myogenic tone, and partially suppressed a
      component of contraction at elevated transmural pressures in arterioles incubated
      in 1 microM PE/1 mM TEA/100 microM NfA. CONCLUSIONS: Our data indicate that under
      low to moderate stimulation of the alpha1-adrenoceptor signaling pathway,
      I(Cl(Ca)) channels play an important role in the sustained contraction produced.
      Their declining contribution to contraction with increasing transmural pressure
      may be explained, at least in part, by a progressive enhancement of stretch
      induced ionic conductances, possibly volume-sensitive Cl- channels.

PMID- 10912467
TI  - An inward rectifier and a voltage-dependent K+ current in single, cultured
      pericytes from bovine heart.
AB  - OBJECTIVE: The purpose of this study was to describe passive electrical
      properties and major membrane currents in coronary pericytes. METHODS: 78 single,
      cultured bovine pericytes were studied with the patch-clamp technique in the
      whole-cell mode. RESULTS: The membrane potential of the cells was -48.9+/-9.6 mV
      (mean+/-S.D.) with 5 mM and -23.2+/-2.2 mV with 60 mM extracellular K+. The
      membrane capacitance was 150.2+/-123.2 pF. The current-voltage relation of the
      pericytes was dominated by an inward current at hyperpolarized potentials and an
      outward current at depolarized potentials. Increasing extracellular K+ from 5 to
      60 mM led to an increase of the inward current and to a shift of this current to
      more depolarized potentials. The inward current was very sensitive to
      extracellular barium (50 microM). The maximum slope conductance of the cells at
      hyperpolarized potentials was 2.9+/-2.8 nS. Inward rectification of whole-cell
      currents was steep (slope factor = 6.8 mV). With elevated external K+ the outward
      current reversed near the potassium equilibrium potential. Onset of the outward
      current was sigmoid and inactivation of this current was monoexponential, slow
      (time constant = 12.8 s) and incomplete. Voltage-dependence of outward current
      steady-state activation was steep (slope factor = 4.6 mV). The outward current
      was very sensitive to 4-aminopyridine (dissociation constant = 0.1 mM). The
      maximum slope conductance at depolarized potentials was 16.6+/-15.6 nS.
      CONCLUSION: We report for the first time, patch-clamp recordings from coronary
      pericytes. An inward rectifier and a voltage-dependent K+ current were identified
      and characterized. Regulation of these currents may influence coronary blood
      flow.

PMID- 10912468
TI  - 17Beta-estradiol modulates endothelin-1 expression and release in human
      endothelial cells.
AB  - OBJECTIVE: In this study the role of 17beta-estradiol (E2) in the regulation of
      endothelin-1 (ET-1) mRNA expression and secretion was investigated in cultured
      human umbilical vein endothelial cells (HUVECs). METHODS: Endothelial cells were
      either deprived of or treated with 17beta-estradiol (10(-9), 10(-7) M) for 48 h.
      After the incubation, the effect of E2 on ET-1 gene expression was evaluated by
      Northern blot analysis. ET-1 release into the media was measured by
      radioimmunoassay after 6 h of incubation under basal conditions and upon
      stimulation with thrombin (4 U/ml). In addition, the cyclic guanosine 5'
      monophosphate (cGMP) content of cells was assayed by immunoassay. In order to
      exclude the role of nitric oxide (NO) in E2-induced effects on endothelin-1 gene
      expression and secretion, nitric oxide synthase (NOS) inhibitor, N-nitro L
      arginine methyl ester (1 mM) (L-NAME) was added to the media of some cultures.
      RESULTS: Incubation of HUVECs with 10(-9) and 10(-7) M E2 for 48 h resulted in a
      30 and 47% inhibition of ET-1 mRNA expression, respectively. Incubation with E2
      also decreased the basal and thrombin-stimulated ET-1 release while increasing
      the cGMP content of cells significantly. NOS inhibitor L-NAME increased the
      release of ET-1 from E2-incubated cells but did not alter the ET-1 release from
      hormone-deprived cells. However, ET-1 secretion of E2-treated cells were
      significantly less than the deprived ones. Northern blot analyses also
      demonstrated that inhibition of NOS only partly attenuated the effect of E2 on ET
      1 gene expression. In the presence of L-NAME, treatment with 10(-7) M E2 caused a
      12% decrease in ET-1 gene expression. CONCLUSION: The results demonstrate that E2
      may play both direct and indirect role in regulation of ET-1 gene expression and
      production in human endothelial cells. E2-induced increase in NO but decrease in
      ET-1 production may partly explain the mechanism of the protective effects of the
      hormone on the cardiovascular system.

PMID- 10912469
TI  - In vitro evaluation of c7E3-Fab (ReoPro) eluting polymer-coated coronary stents.
AB  - OBJECTIVE: Stent thrombosis and in-stent restenosis remain problematic in certain
      patient sub-groups. c7E3-Fab (ReoPro, abciximab) inhibits the platelet
      glycoprotein IIb/IIIa receptor as well as the smooth muscle cell alpha(v)beta3
      receptor, and thus may influence both processes, especially if high local
      concentrations could be achieved. We have studied the adsorption and elution
      characteristics of c7E3-Fab on commercially available polymer-coated stents. We
      have also investigated the effect of such antibody binding on platelet deposition
      in vitro, and on antibody deposition into ex vivo human saphenous vein wall to
      assess whether such stents may influence stent thrombosis and restenosis. METHODS
      AND RESULTS: Adsorption was measured using a radioisotope technique after
      immersing segments of polymer-coated stents in c7E3-Fab solutions. Uptake was
      dependent on antibody concentration and duration of immersion of wire in the
      solution. After 22 h (at 5 mg ml(-1)), 1146+/-101 ng cm(-1) wire was adsorbed. In
      an in vitro perfusion circuit, the antibody eluted slowly, with 53% remaining
      after 12 days washing. To determine the value that such stents might have in
      clinical practise, adsorption to balloon-mounted stents was assessed at room
      temperature, using commercially available c7E3-Fab (2 mg ml(-1)). Efficacy of
      eluting c7E3-Fab was determined by measuring deposition of 111-Indium platelets.
      Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3%
      compared to controls (P=0.018). Deployment of treated stents in ex vivo saphenous
      vein resulted in the deposition of c7E3-Fab in the intima and media. CONCLUSIONS:
      c7E3-Fab can be passively adsorbed onto polymer-coated stents. It elutes slowly
      and in a predictable manner, significantly inhibiting platelet deposition in
      vitro. These studies pave the way to developing stent-based delivery of a potent
      anti-platelet agent that may additionally affect smooth muscle cell activity.

PMID- 10912470
TI  - Altered expression of natriuretic peptide receptors in proANP gene disrupted
      mice.
AB  - BACKGROUND: The atrial natriuretic peptide (ANP) family is a complex system
      consisting of at least three polypeptides and at least three types of receptor.
      Each peptide interacts with different types of receptor at varying degrees of
      affinity. To determine if natriuretic peptide levels influence natriuretic
      peptide receptor expression and regulation, we examined the expression of
      guanylyl cyclase linked GC-A, GC-B and C-receptor in the lungs of mice with a
      mutation that inactivates the ANP gene (Nppa). METHODS: The mRNA level of GC-A,
      GC-B and C-receptor in the lung were studied by ribonuclease protection assays
      (RPA). RESULTS: Results of RPA showed that although the mRNA level of GC-A and GC
      B of heterozygous ANP+/- was not different from wild type ANP+/+ mice, they were
      significantly higher in the homozygous mutant ANP-/- mice. In addition, C
      receptor mRNA level in ANP+/- and ANP-/- was significantly lower than ANP+/+
      mice. The C-receptor results were confirmed by receptor binding assays and
      affinity cross-linking studies. CONCLUSIONS: Taken together these data suggest
      that permanent removal of ANP from the natriuretic peptide system results in an
      up-regulation of GC-A and GC-B, and a corresponding down-regulation of C-receptor
      in the lung of proANP gene disrupted mice. We postulated that changes in the
      natriuretic peptide receptor population may result in chronic hypertension and
      cardiac hypertrophy in the ANP-/- mice.

PMID- 10912471
TI  - Re: 'Ventricular arrhythmias induced by endothelin-1 or by acute ischemia: a
      comparative analysis using three dimensional mapping' (Cardiovasc Res 2000;45:310
      320).

PMID- 10912472
TI  - In-patient assessment of difficult diarrhoea.
AB  - 'Diarrhoea' remains a common problem presented to gastroenterologists. Assessment
      of the history will in most cases point to the investigations that will
      distinguish between organic and functional causes and lead to diagnosis. There
      exists a small group of patients either in whom there may be difficulties in
      distinguishing between organic and functional causes, or in whom a diagnosis of
      factitious diarrhoea is suspected. These patients should be admitted for a short
      in-patient assessment and undergo an analysis of 72-h stool weights. If these are
      less than 225 g/ day a functional cause should be suspected. If they are raised,
      then further investigations to exclude a factitious cause should include analysis
      of fluid balance, stool osmolality and stool electrolyte and creatinine content.
      A laxative screen should also be performed according to available quality control
      guidelines.

PMID- 10912473
TI  - Neuropathy in the brain-in-the-gut.
AB  - * The enteric nervous system has sensory neurons, interneurons and motor neurons
      and functions as a brain-in-the-gut. * Smooth muscles of the digestive tract are
      autogenic in the absence of neural control. * Enteric inhibitory motor neurons
      control excitability of the autogenic musculature. * The neuropathic form of
      chronic intestinal pseudo-obstruction is a form of disinhibitory motor disease
      linked with neuropathic degeneration in the enteric nervous system. * Patients
      with inflammatory degenerative neuropathy may progress from irritable bowel
      syndrome (IBS)-like symptoms to chronic pseudo-obstruction. * Detection of anti
      enteric neuronal antibodies may be a useful diagnostic test for early stages of
      inflammatory degenerative neuropathy in patients with symptoms of a functional
      gastrointestinal disorder. Awareness is increasing that autoimmune attack
      targeted to neuronal elements of the enteric nervous system may underlie
      irritable bowel-like symptoms that progress to chronic pseudo-obstruction. The
      inflammatory neuropathy disrupts the integrative functions of the brain-in-the
      gut, including reduction in the population of inhibitory motor neurons to the
      musculature. Extreme loss of inhibitory motor neurons is manifest as
      disinhibitory motor disease characterized by achalasia in smooth muscle
      sphincters and hyperactive, disorganized contractile behaviour of intestinal
      circular muscle which results in pseudo-obstruction. Detection of anti-enteric
      neuronal antibodies in the serum of patients with early symptoms of a functional
      gastrointestinal motility disorder may prove to be a useful diagnostic test for
      inflammatory enteric neuropathy.

PMID- 10912474
TI  - Helicobacter pylori gastritis in Africa.
AB  - * Helicobacter pylori gastritis progresses to gland loss and intestinal
      metaplasia in a considerable proportion of colonized subjects. * The progression
      to atrophic gastritis is a slow process, occurring with an incidence of 1-2% per
      year. * The progression of chronic H. pylori gastritis is the same in Africa as
      in Europe and South America. * This supports the concept of H. pylori as a
      causative factor of pre-neoplastic conditions of the gastric mucosa; other
      factors must play a modulating role in the progression to cancer. H. pylori
      gastritis may progress to atrophic gastritis and lead to the development of
      intestinal metaplasia, dysplasia and eventually gastric cancer in a minority of
      subjects. The available data on the kinetics of H. pylori gastritis are limited,
      but nevertheless very consistent. They suggest that the progression to gland loss
      or atrophic gastritis among H. pylori-positive subjects occurs at a rate of 1-2%
      per year. As H. pylori gastritis usually persists for life, a considerable
      proportion of H. pylori-positive subjects thus eventually show signs of gastric
      gland loss. The majority of these subjects progress to intestinal metaplasia.
      Despite these consistent findings in different areas of the world, the incidence
      of gastric cancer is only moderately related to the prevalence of H. pylori. An
      example is the so-called African enigma, referring to a low incidence of gastric
      cancer in certain countries of Africa, despite a high prevalence of H. pylori in
      all age groups. This is not due to differences in progression to atrophic
      gastritis; other yet unidentified factors therefore must play a role.

PMID- 10912475
TI  - Is villous atrophy always and only the result of gluten sensitive disease of the
      intestine?
AB  - 'Flat and flexible truths are beat out by every hammer' (Sir Thomas Browne,
      writer and physician) The prevalence of gluten-sensitive enteropathy (GSE) or
      coeliac disease is likely to be as high as 1:200 to 1:400 in the developed world.
      Current medical practice leaves a significant proportion of these cases
      undiagnosed. An association between untreated coeliac disease and intestinal
      malignancy is well described so it is possible that patients with undiagnosed
      coeliac disease constitute a significant reservoir of preventable
      gastrointestinal malignancy. However, it is not clear whether all patients with
      coeliac disease are equally at risk of malignancy nor are all cases of intestinal
      malignancy necessarily associated with wheat protein sensitivity. Thus the
      precise links between GSE, villous atrophy and malignancy have not yet been
      established. However, there is evidence that products of activated T-cell clones,
      be they antigen specific or malignant, influence epithelial cell proliferation,
      differentiation and function thus contributing to the histological lesion
      characteristic of GSE or small bowel lymphoma.

PMID- 10912476
TI  - Dilutional diarrhoea: under-diagnosed and over-investigated.
AB  - We report two cases of factitious diarrhoea caused by stool dilution. In the
      first report stools from a patient with chronic diarrhoea were found to have been
      diluted with urine, and the diarrhoea further compounded by surreptitious
      laxative misuse. In the second report, after prolonged investigation of high
      output ileostomy, the patient's ileal effluent was found to have been diluted
      with water. We conclude that factitious diarrhoea, in particular dilutional
      diarrhoea, is over-investigated and underdiagnosed. Stool weights, complete
      input/output measurement, analysis of stool osmolality and electrolytes, and
      laxative screening are essential in the investigation of chronic watery
      diarrhoea.

PMID- 10912477
TI  - Idiopathic myenteric ganglionitis underlying intractable vomiting in a young
      adult.
AB  - Inflammatory infiltration of intestinal myenteric plexuses (i.e. myenteric
      ganglionitis), along with severe intestinal motor abnormalities, may accompany
      paraneoplastic syndromes, neurological disorders and gastrointestinal infections,
      although rare cases can be idiopathic. In this report, we describe the case of a
      patient who presented with chronic intractable vomiting and weight loss
      associated with idiopathic myenteric ganglionitis mainly involving the stomach.
      Tissue analysis showed that the inflammatory infiltrate comprised T lymphocytes
      (CD4+ and CD8+), and peptide immunolabelling revealed a marked decrease of
      substance P/tachykinin immunoreactive staining in nerve fibres and myenteric
      neurones. Following systemic steroid therapy, the patient's symptoms dramatically
      improved, and after one year of follow-up his general condition remains
      satisfactory. The possible mechanisms leading to symptom generation and gastric
      dysmotility in the context of an idiopathic myenteric ganglionitis are discussed.

PMID- 10912478
TI  - Trends over time in Helicobacter pylori gastritis in Kenya.
AB  - OBJECTIVE AND DESIGN: There is increasing evidence to link infection of the
      gastric mucosa by Helicobacter pylori with the subsequent development of gastric
      cancer. This study was undertaken to document the progression of H. pylori
      gastritis in a rural Kenyan population with a moderate gastric cancer risk.
      METHOD: Biopsy follow-up study of 51 H. pylori-positive patients over an average
      of 5.5 years. RESULTS: In the study group, the number of individuals with
      moderate to severe atrophy rose from 17 (33%) to 22 (43%), an annual increase of
      1.8% [95% confidence interval (CI) -0.9% to 4.4%]. There was significant
      progression of atrophy (P< 0.05) in those with low overall scores for graded
      morphological variables at initial endoscopy. Intestinal metaplasia did not
      progress; indeed four out of 12 patients initially diagnosed with intestinal
      metaplasia showed no evidence of it in their follow-up biopsies. CONCLUSIONS: H.
      pylori gastritis with atrophy may provide a suitable environment within the
      gastric mucosa for the development of gastric cancer but it is likely that other
      factors in this population determine further progress towards dysplasia and
      cancer.

PMID- 10912479
TI  - Evidence favouring the gastro-oral route in the transmission of Helicobacter
      pylori infection in children.
AB  - OBJECTIVE: Several studies support the view that Helicobacter pylori is acquired
      in early life and within families. However, the exact route of transmission
      remains unknown. Given that H. pylori colonizes only the human gastric mucosa,
      the hypothesis that history of vomiting in siblings may be a relevant risk factor
      was tested in a paediatric setting. METHODS: One hundred urban children (age
      range 0.8-16.6 years, median 9), 44% with evidence of active H. pylori infection,
      were recruited. A structured questionnaire dealing with socio-economic issues was
      completed. Vomiting siblings and siblings of vomiting index children were
      screened for H. pylori by means of (13)C-urea breath test. Serum samples from
      index children were assayed for immunoglobulin G to hepatitis A (HAV) and Epstein
      Barr virus (EBV) in order to check for faecal-oral and oral-oral exposure,
      respectively. RESULTS: Vomiting siblings of H. pylori-infected index children and
      siblings of H. pylori-infected vomiting index children had a high rate of active
      H. pylori infection (60 and 67%, respectively). History of vomiting in siblings
      was positively associated with active H. pylori infection in the index children
      (multivariate odds ratio 2.4, 95% confidence interval 1.3-4.3). Seropositivity
      for HAV and EBV was found in 1 and 68 index children, respectively. The agreement
      between active H. pylori infection and EBV seropositivity was not significant
      (kappa = 0.26). CONCLUSIONS: History of vomiting in siblings is an independent
      risk factor for H. pylori. Nowadays, transmission of H. pylori in urban children
      may involve the gastro-oral route more than the faecal-oral or oral-oral
      pathways.

PMID- 10912480
TI  - Comparison of tests for assessment of Helicobacter pylori eradication: results of
      a multi-centre study using centralized facility testing.
AB  - BACKGROUND: The accuracy of diagnostic tests to assess Helicobacter pylori
      eradication has rarely been performed. AIM: To compare the tests most commonly
      used for this purpose, i.e. histology, culture and (13)C urea breath test
      performed in centralized facilities. METHODS: Prospective study where patients
      were included in four centres and diagnostic tests performed centrally by
      biologists experienced in the field. Gastric biopsies were obtained from antrum
      and corpus (two for histology, two for culture from each site) 4-6 weeks after an
      eradication treatment. The definition of a gold standard for H. pylori-positive
      patients was either a positive culture or both positive histology and urea breath
      test results. RESULTS: Ninety-seven patients for whom data on histology, culture
      and (13)C urea breath test were available were included. The majority were
      females (60%) suffering from non-ulcer dyspepsia (52%) and having received proton
      pump inhibitor-based triple therapy (62%). Forty-one per cent of the patients
      were H. pylori-positive according to the gold standard. The sensitivities were
      90%, 95% and 92.5% and the specificities 100%, 98.2% and 100% for culture,
      histology and (13)C urea breath test, respectively. CONCLUSION: All the methods
      had excellent specificity but the sensitivity ranged between 90 and 95%. The
      combination of two techniques which increases the sensitivity to virtually 100%
      is recommended in situations where the eradication treatment requires a precise
      evaluation such as in clinical trials.

PMID- 10912481
TI  - Non-Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese
      population.
AB  - BACKGROUND: Helicobacter pylori and non-steroidal anti-inflammatory drugs
      (NSAIDs) are recognized as the major causes of peptic ulcer disease. The status
      of H. pylori infection in the background population may influence the incidence
      of H. pylori-negative peptic ulcer disease. OBJECTIVE: To examine the incidence
      of H. pylori-negative peptic ulcer disease without intake of NSAIDs in Japan.
      PATIENTS: A total of 398 patients who had no eradication therapy for H. pylori
      prior to this study, including 246 patients with gastric ulcer (GU) and 152
      patients with duodenal ulcer (DU), were enrolled. METHODS: H. pylori status was
      assessed by rapid urease tests, histological examinations (haematoxylin & eosin
      stain, Giemsa stain and/or immunostaining) and serum IgG antibody. Two biopsy
      specimens were taken from the antrum within 3 cm of the pyloric and two from the
      middle corpus of the stomach, along the greater curvature. Patients were asked a
      series of questions regarding risk factors, including the use of NSAIDs. The
      presence of gastritis, gastric atrophy and intestinal metaplasia was examined
      according to the updated Sydney system. RESULTS: Of the 246 patients with GU, 12
      patients (4.9%) were considered to be H. pylori-negative. Of the 152 patients
      with DU, two patients (1.3%) were considered to be H. pylori-negative. Hence, a
      total of 14 patients were found to be H. pylori-negative. Nine of them were
      taking NSAIDs. Consequently, the frequency of H. pylori-negative ulcer without
      intake of NSAIDs was 1.3%. There was no significant difference in the frequencies
      of H. pylori-negative patients between the GU and DU groups. CONCLUSION: The
      incidence of H. pylori-negative peptic ulcer disease without intake of NSAIDs was
      very low in the Japanese population.

PMID- 10912482
TI  - Helicobacter pylori increases gastrin release from cultured canine antral G
      cells.
AB  - OBJECTIVE: To investigate the mechanisms underlying the hypergastrinaemia of
      Helicobacter pylori by examining the effects of H. pylori on basal and stimulated
      gastrin release from cultured canine G-cells. METHODS: Canine antral G-cells were
      prepared by collagenase-EDTA digestion and cultured for 40 h. G-cells were then
      cultured for a further 24 h with two different H. pylori sonicates before basal
      and bombesin-stimulated gastrin release were measured by radioimmunoassay.
      RESULTS: Treatment of G-cells with both H. pylori sonicates significantly
      enhanced basal gastrin release (by 17-27%) and bombesin-stimulated gastrin
      release (by 115-133%). This effect was independent of cagA and vacuolating
      cytotoxin status. Control treatment with Escherichia coli sonicate had no effect
      on gastrin release. There was no change in the cellular content of gastrin.
      CONCLUSIONS: Incubation of antral G-cells with H. pylori constituents enhances
      subsequent basal and bombesin-stimulated gastrin release. Direct contact between
      H. pylori and G-cells in the gastric antrum may be responsible for the
      hypergastrinaemia seen with the infection.

PMID- 10912483
TI  - Small bowel lymphoma in unrecognized coeliac disease: a cause for concern?
AB  - BACKGROUND AND AIM: It is not clear whether the increased risk of small bowel
      lymphoma seen in typical coeliac disease also applies to unrecognized or
      screening-detected coeliac patients. The aim of the present study was to
      determine the features of small bowel lymphoma and whether it is associated with
      unrecognized coeliac disease at the time of presentation. DESIGN: A retrospective
      search by the five pathology laboratories serving Northern Ireland, UK. METHODS:
      Snomed searches were used to identify cases of adenocarcinoma (SBA) and lymphoma
      (SBL) affecting the small intestine between 1987 and 1996. Pathology reports were
      obtained and analysed with respect to the clinical features, site of pathology,
      type of tumour, grading and the presence or absence of distant villous atrophy.
      RESULTS: One hundred and thirty-eight cases were identified of whom 69 (44 men;
      mean age 60.2 years) were SBL and 69 (41 men; mean age 68.0 years) were SBA.
      Comparing the SBL to the SBA group the clinical presentation was perforation (10
      vs 1, P= 0.009), small intestinal obstruction (20 vs 20, P= 1.0) and small
      intestinal mass (13 vs 15, P= 0.67). B-cell lymphomas occurred in 20 cases, T
      cell lymphomas in 24 cases and 25 were unclassified. There was one known coeliac
      patient in the SBL group and none in the SBA group (P = 1.0). Villous atrophy at
      a distant site was recorded in 13 patients in the SBL group compared to none in
      the SBA group, all of these patients having T-cell lymphomas. CONCLUSIONS:
      Similar numbers of SBL and SBA occurred in the study period. Their clinical
      presentation was similar although perforation was more common in the SBL group.
      One-third of all SBL patients (over half of T-cell lymphomas) had distant villous
      atrophy, indicating that small bowel lymphoma appears to be significantly
      associated with unrecognized coeliac disease.

PMID- 10912484
TI  - Barrett's oesophagus: results from a 13-year surveillance programme.
AB  - OBJECTIVES: To review the results of a 13-year surveillance programme of patients
      with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although
      the risk of cancer in Barrett's oesophagus is well established, the magnitude of
      this risk is still controversial. DESIGN: Records of all patients with
      histologically confirmed Barrett's oesophagus in our 13-year surveillance
      programme were examined retrospectively. SETTING: Integrated gastroenterology and
      gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS:
      During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of
      these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN
      OUTCOME MEASURES: The development of oesophageal adenocarcinoma. RESULTS: After a
      mean follow-up of 43 months, 12 patients, all with specialized epithelium,
      developed adenocarcinoma (11 men), an incidence for men of one cancer per 69
      patient-years; and for women, one cancer per 537 patient-years follow-up (P <
      0.01). If only patients with specialized mucosa were included the incidence of
      cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years;
      women, one per 468 patient-years). CONCLUSIONS: Whilst the role of screening
      patients with Barrett's oesophagus remains controversial, this study supports the
      routine surveillance of male patients with specialized epithelium.

PMID- 10912485
TI  - The effect of lifestyle changes on results of 24-h ambulatory oesophageal pH
      monitoring.
AB  - OBJECTIVES: Twenty-four-hour pH monitoring is the 'gold standard' investigation
      of gastro-oesophageal reflux disease. It has been suggested that results may be
      influenced by lifestyle alteration during the study. The aim of this study was to
      determine the influence of lifestyle alteration and anxiety on outcome in pH
      monitoring. METHODS: One hundred consecutive patients attending for pH monitoring
      were recruited. Post-intubation anxiety was quantified (STAI form Y-1). On
      completion a questionnaire was recorded comprising six questions regarding
      alteration to eating/drinking (FOOD) (score 0-6) and six regarding posture and
      activity (ACTIVITY) (score 0-6). The higher the score the greater the alteration
      of lifestyle. A 10-point visual analogue scale (VAS) scored the degree of
      distress caused by the experience. pH studies were positive if exposure times at
      pH < 4 were greater than established normal values or if the Symptom Index was >
      50%. Comparisons were made between patients with positive and negative studies
      regarding FOOD, ACTIVITY, VAS and STAI scores. RESULTS: Patients with positive pH
      studies had mean FOOD (2 vs 2; P> 0.05), ACTIVITY (2 vs 2; P> 0.05), VAS (3 vs 3;
      P> 0.05) and STAI (31 vs 32; P> 0.05) scores which were not significantly
      different from those of patients with negative pH studies. CONCLUSIONS: Lifestyle
      alteration was minimal in patients undergoing pH monitoring, nor was the
      experience distressing. There was no difference in lifestyle alteration and
      anxiety between those with positive and negative pH profiles.

PMID- 10912486
TI  - Audit of cyclosporin use in inflammatory bowel disease: limited benefits,
      numerous side-effects.
AB  - BACKGROUND: The failure of standard treatments for inflammatory bowel disease
      (IBD) has led to the use of immuno-modulatory therapy. Most reports of the use of
      cyclosporin are from single specialist centres. AIM: To survey the use of
      cyclosporin in IBD in Bristol's three teaching hospitals. PATIENTS AND METHODS:
      Over a 4-year period, all patients receiving cyclosporin for IBD were identified
      and the following data recorded: diagnosis, duration of disease, initial
      treatment, date initiated, dose of cyclosporin, side-effects, initial clinical
      response, and current patient status. RESULTS: Thirty-three patients were
      identified, of whom 26 had ulcerative colitis (UC), six had Crohn's disease and
      one had indeterminant colitis. The most frequent indication was as 'rescue'
      therapy in acute severe UC. The overall initial response rate was 63%, but this
      was only maintained in 30% long-term patients, with over half of them reporting
      side-effects. Four patients had life threatening side-effects. CONCLUSION:
      Although the initial response rates are encouraging, the long-term results are
      poor and at the expense of a high incidence of side-effects. We feel that the use
      of cyclosporin in IBD should be reconsidered until more information from
      randomized controlled studies becomes available.

PMID- 10912487
TI  - How frequently do large bowel diverticula perforate? An incidence and cross
      sectional study.
AB  - The aetiology of perforation of large bowel diverticula is poorly understood and
      a case-control study is required to identify the causes. Before such a study can
      be attempted, the incidence must be determined and groups at particular risk
      identified. Cases of perforated large bowel diverticula living in the Norwich
      postal code region treated between 1995 and 1997 were identified. Fifty-eight
      cases presented in a population of 531 241. The incidence was 4.0 cases per
      100,000 per year, increased with age and was higher in men than women (5.8 vs
      3.1). The most frequently used drugs were non-steroidal anti-inflammatory drugs
      (NSAIDs) (29%) and opiate analgesics (26% of cases). This is the first report of
      the incidence of perforated diverticular disease and allows a calculation of the
      population size needed to recruit sufficient cases for an aetiological
      investigation. The differences in incidence between genders should prompt a
      search for factors which differ between the sexes such as diet. NSAIDs are a
      known risk factor, although the data show that opiate analgesics should be
      investigated.

PMID- 10912488
TI  - Epidemiology of hepatitis C virus infection in seven European Union countries: a
      critical analysis of the literature. HENCORE Group. (Hepatitis C European Network
      for Co-operative Research.
AB  - Hepatitis C is now recognized as the most common infection causing chronic liver
      disease in the European population. Our aim was to assess the prevalence of the
      antibody to hepatitis C virus (HCV), and the incidence of HCV seroconversion in
      the general population and the main risk groups, namely intravenous drug users,
      haemodialysis and transfused patients, in seven countries of the European Union,
      by carrying out a critical analysis of the literature. Data sources used were the
      Medline database and a manual search using the key words: hepatitis C,
      prevalence, incidence, transmission, risk factors and epidemiology. Articles
      published between January 1990 and March 1997 were reviewed. Articles were
      reviewed according to a critical analysis method regarding title, type of
      article, study design, period and population, tests, results and their
      consistency with data. The tests performed were mainly second- or third
      generation serological tests. The average prevalence rate in blood donors was 1%,
      with a north-south gradient ranging from 0.04% to 2%. Prevalence varied from 20%
      to 30% in haemodialysis patients. The incidence in transfused patients was less
      than 1% after 1991. The prevalence in intravenous drug users was about 80%.
      Multicentre studies conducted in larger samples are needed to obtain more
      accurate and reliable results, in particular. However, the epidemiological
      studies available allowed us to assess the magnitude of HCV infection in Europe.

PMID- 10912489
TI  - Rapid effects of lipopolysaccharides on indocyanine green clearance in rat liver.
AB  - BACKGROUND: Lipopolysaccharides (LPSs) are thought to be one of the triggers of
      organ reactions to sepsis, which causes hepatocellular dysfunction. This
      dysfunction can be demonstrated by a reduction of organic anion transport. The
      aim of our study was to assess whether the transport of indocyanine green (ICG)
      is affected by LPS, and whether Kupffer cells are involved. METHODS: Single-pass
      liver perfusion with ICG at a concentration of 57.8 mg/kg/min was performed for
      130 min. pH, oxygen tension and perfusion pressure were continuously measured in
      influent and effluent. Taurocholate was infused at 48.3 mg/kg/min to achieve a
      stable bile flow. LPS was added at concentrations of 0.45, 0.9 and 1.44 mg/kg/min
      for 30 min. ICG was determined photometrically in perfusate and bile. To depress
      the function of Kupffer cells male Wistar rats were treated with GdCl3 24 h in
      advance. Primary cultured hepatocytes were used for studying the direct effect of
      LPS on the uptake rate of ICG. RESULTS: Forty-five minutes after administration
      of LPS a significant dose-dependent decrease of ICG uptake was seen in animals
      treated with LPS. Livers of animals pretreated with GdCl3 did not show this
      decrease. LPS had no direct effect on the uptake of ICG into primary cultured
      hepatocytes, whereas treatment of these cells with 8-bromo-cGMP resulted in a
      significant increase of ICG uptake. CONCLUSION: LPS has a rapid dose-dependent
      effect on the detoxification properties of the liver for ICG. The rapid effect of
      LPS on ICG uptake in hepatocytes is mediated by Kupffer cells.

PMID- 10912490
TI  - Factors predictive of liver cirrhosis in patients with chronic hepatitis B: a
      multivariate analysis in a longitudinal study.
AB  - OBJECTIVE AND DESIGN: Chronic hepatitis B virus (HBV) infection may lead to liver
      cirrhosis; however, factors associated with the development of cirrhosis have
      been incompletely studied. A total of 516 patients with chronic hepatitis B were
      followed up longitudinally to determine their outcome. METHODS: The clinical and
      pathological features were compared between those with and without cirrhosis
      occurrence. The risk factors were analysed, and the probability of the
      development of cirrhosis was estimated. RESULTS: During a mean follow-up period
      of 5.7 +/- 3.4 years (range 1-17 years), cirrhosis occurred in 71 patients, with
      a calculated annual incidence of 2.4%. Older age (> 45 years) at entry, male
      gender, persistent hepatitis (> 1.5-fold rise of serum alanine aminotransferase
      levels for at least one year) and diabetes mellitus were identified as
      independent risk factors of cirrhosis in a multivariate analysis (odds ratios
      8.0, 19.3, 2.0 and 5.2, respectively; P values all < 0.05). A logistic regression
      equation was used to predict the probability of cirrhosis occurrence, which was
      as high as 76.6% when all risk factors were present. Acute exacerbation or super
      infection by hepatitis C or D viruses were not significant predictors. Patients
      with subsequent cirrhosis had higher initial hepatic histological necro
      inflammatory activities when compared to age- and sex-matched non-cirrhotic
      controls (Knodell's scores: 8.2 +/- 2.4 versus 6.0 +/- 4.1, P< 0.05).
      CONCLUSIONS: Patients who were elderly, male, diabetic or had a history of
      persistent and histologically severe hepatitis were at increased risks of liver
      cirrhosis. Aggressive anti-viral therapy may be needed for these patients and
      they should be closely monitored for HBV-related late complications.

PMID- 10912491
TI  - Risk factors for the development of gallstone recurrence following medical
      dissolution. The British-Italian Gallstone Study Group.
AB  - OBJECTIVE: To assess risk factors for gallstone recurrence following non-surgical
      treatment. DESIGN: A prospective follow-up of a multicentre cohort of post
      dissolution gallstone patients. SETTING: Six gastroenterology units in the UK and
      Italy. PARTICIPANTS: One hundred and sixty-three patients with confirmed
      gallstone dissolution following non-surgical therapy (bile acids or lithotripsy
      plus bile acids), followed up by ultrasound scan and clinical assessment at 6
      monthly intervals for up to 6 years (median, 25 months; range, 6-70 months).
      OUTCOME MEASURES: Subject-related variables (sex, age, height, weight, body mass
      index), gallstone-related variables (number, diameter, presence of symptoms,
      months to complete stone clearance), treatment modalities (bile acid therapy,
      extracorporeal shock wave lithotripsy) and follow-up related variables (weight
      change, use of non-steroidal anti-inflammatory agents, statins, pregnancies
      and/or use of oestrogens) were assessed by univariate and multivariate analysis
      as putative risk factors for gallstone recurrence. RESULTS: Forty-five gallstone
      recurrences were observed during the follow-up period. Multiple primary
      gallstones and length of time to achieve gallstone dissolution were the only
      variables associated with a significant increase in the recurrence rate.
      Appearance of biliary sludge during follow-up was also significantly related to
      development of gallstone recurrence. Use of statins or non-steroidal anti
      inflammatory agents did not confer protection against recurrence. CONCLUSIONS:
      Patients with primary single stones are the best candidates for non-surgical
      treatment of gallstones, because of a low risk of gallstone recurrence. The
      positive association of recurrence with biliary sludge formation and time to
      dissolution of primary stones may provide indirect confirmation for the role of
      impaired gallbladder motility in the pathogenesis of this condition.

PMID- 10912492
TI  - A 'palliative' resection which became potentially curative.
AB  - We report a very unusual case of a woman with rectal cancer, who, at operation,
      appeared to have peritoneal metastases. An anterior resection was carried out,
      and subsequent histology showed the rectal tumour to be a well-differentiated
      Dukes' B adenocarcinoma, which had been completely excised. The apparent
      'metastases' were found to be schistosomal granulomas and there was also a
      schistosomal granuloma within the tumour.

PMID- 10912493
TI  - Infected hepatic cyst in a patient with multiple hepatic cysts: report of a case
      diagnosed by change of ultrasonographic findings.
AB  - Liver cysts are commonly observed, but infection of a liver cyst is a rare
      complication. Although patients have clinical symptoms, such as a high-grade
      fever and abdominal pain, diagnosing an infected cyst by abdominal
      ultrasonography, computed tomography (CT) with contrast medium and magnetic
      resonance imagings (MRI) is not always easy. We experienced an unusual case who
      had only clinical symptoms, such as high-grade fever and a right quadrant
      abdominal pain, but no imaging findings when admitted. Careful observation using
      ultrasonography once a week revealed signs of an infected cyst containing
      echogenic fluid 32 days after admission. We performed percutaneous transhepatic
      cystic drainage. When a patient has liver cysts and complains of high-grade fever
      and abdominal pain, liver cysts should be considered as a focus of sepsis, and we
      recommend repeat use of ultrasonography or CT, even if no typical findings occur
      the first time.

PMID- 10912494
TI  - Cirrhosis in Turner's syndrome: case report and literature review.
AB  - A case of cryptogenic cirrhosis in a patient with Turner's syndrome is presented.
      The individual was admitted for upper gastrointestinal bleeding due to
      oesophageal varices. After failure of medical treatment, a transjugular intra
      hepatic portal systemic shunt was used to control the bleeding. A liver biopsy
      revealed cirrhosis with minimal necro-inflammatory activity and no steatosis.
      Immunohistochemical staining for HCV, HBsAg and HBcAg was negative. No other risk
      factor for liver disease was recognized and none of the known causes of chronic
      liver disease was identified after a thorough evaluation for such. Turner's
      syndrome is a genetic disorder due to X chromosome monosomy in which a wide range
      of congenital anomalies can occur. Cardiac, renal and skeletal anomalies are all
      well recognized. The possible association of Turner's syndrome with cirrhosis is
      herein discussed along with a review of the published literature.

PMID- 10912495
TI  - Fludarabine induced intestinal pseudo-obstruction: case report and literature
      review.
AB  - Intestinal pseudo-obstruction is a recognized but rare complication of
      chemotherapy. Vinca alkaloids and cytarabine have been reported to be associated
      with intestinal pseudo-obstruction. We report a case of fludarabine induced
      severe intestinal pseudo-obstruction in a 66-year-old man suffering from non
      Hodgkin's lymphoma, and describe our successful management of this with a
      combination of parasympathomimetic and mechanical decompression, after failure of
      conservative management.

PMID- 10912496
TI  - Depression and control beliefs in relation to reemployment: what are the
      directions of effect?
AB  - Depressive symptoms, locus of control, and reemployment were assessed over the
      course of 1 year among 254 recently unemployed men and women. Individual growth
      curve modeling and discrete-time survival analyses were used to examine (a)
      whether reemployment resolved depressive symptoms or affected control beliefs,
      (b) whether depressive symptoms or control beliefs predicted time to
      reemployment, and (c) if these relationships changed over time. Depressive
      symptom declines were predicted by reemployment, but initial depression was
      completely unrelated to time to reemployment. Control beliefs were stable over
      time and thus not affected by reemployment. Instead, they predicted early
      reemployment. These processes varied according to reemployment type and time
      period. Implications for intervention and for stress and coping theory are
      discussed.

PMID- 10912497
TI  - Temp-to-permanent employees: a longitudinal study of stress and selection
      success.
AB  - Temp-to-permanent employees are temporary workers who have the opportunity to
      become permanent employees after a specific amount of time (e.g., generally after
      a 3- to 12-month period of trial work). The authors predicted that temporary
      worker individual differences, self-monitoring, tolerance for ambiguity, and role
      adjustment are related to temporary worker physiological stress and to whether
      temporary employees are offered permanent employment. Longitudinal data
      collection (pre- and postentry) resulted in data from 136 temp-to-permanent
      employees. Tolerance for ambiguity and role adjustment were found to be related
      to temporary worker stress and selection success. Self-monitoring was related to
      selection success for workers in an extended probationary period. These results
      suggest the need for further exploration and application of models of stress in
      understanding factors related to temporary worker success.

PMID- 10912498
TI  - Perceptions of safety at work: a framework for linking safety climate to safety
      performance, knowledge, and motivation.
AB  - Research in the areas of organizational climate and work performance was used to
      develop a framework for measuring perceptions of safety at work. The framework
      distinguished perceptions of the work environment from perceptions of performance
      related to safety. Two studies supported application of the framework to employee
      perceptions of safety in the workplace. Safety compliance and safety
      participation were distinguished as separate components of safety-related
      performance. Perceptions of knowledge about safety and motivation to perform
      safely influenced individual reports of safety performance and also mediated the
      link between safety climate and safety performance. Specific dimensions of safety
      climate were identified and constituted a higher order safety climate factor. The
      results support conceptualizing safety climate as an antecedent to safety
      performance in organizations.

PMID- 10912499
TI  - Financial problems and health complaints among farm couples: results of a 10-year
      follow-up study.
AB  - Over a 10-year period, this survey study of 91 Dutch dairy farm couples
      investigated both causal and reversed causal relationships between couples'
      financial problems and husbands' and wives' mental and physical health
      complaints, as well as crossover effects of mental and physical health complaints
      between spouses. These relationships were tested simultaneously using structural
      equation modeling analyses. Results showed that financial problems were not
      predictive of health complaints for either spouse but that husbands' health
      complaints did predict both couples' financial problems and wives' health
      complaints 10 years later. These findings emphasize the importance of mental and
      physical health as resources for both the business and the family. For wives,
      these effects were not found, which may reflect the different positions of
      husbands and wives at the farm and, hence, the different ways they allocate their
      resources.

PMID- 10912500
TI  - The relationships among objective and subjective environmental stress levels and
      serum uric acid: the moderating effect of perceived control.
AB  - This study was designed to investigate the effects of objective and subjective
      stress levels and perceived control on serum uric acid (SUA). Respondents were
      2,504 male and 1,176 female manufacturing employees. Objective job-related stress
      was assessed by the Ergonomic Stress Level (ESL) inventory (S. Melamed, D.
      Yekutieli, P. Froom, E. Kristal-Boneh, & J. Ribak, 1999). As expected, ESL was
      positively associated with SUA, but among male respondents only. The measure of
      subjective stress, environmental annoyance, was negatively related with SUA for
      male respondents, thus not confirming the hypothesis. Perceived control was not
      found to have a direct effect on SUA, after controlling for the ESL measure. For
      male respondents only, perceived control moderated the relationship between ESL
      and SUA: This relationship was negative for those reporting above-average control
      and positive for those reporting below-average control.

PMID- 10912501
TI  - Effects of perceived control on the outcomes of workplace aggression and
      violence.
AB  - This study examined the role of perceived control in ameliorating the negative
      outcomes associated with the experience of violence at work, using 2 large
      samples of hospital staff (N = 187) and group home staff (N = 195). Exploratory
      and confirmatory factor analyses of the measure of perceived control converged in
      suggesting a 3-factor structure consisting of Understanding, Prediction, and
      Influence. Results of a series of moderated regression analyses suggested that
      perceived control did not moderate the relationships between violence and fear or
      between fear and emotional well-being, somatic health, or neglect. However,
      perceived control was directly associated with emotional well-being and
      indirectly associated with somatic health and neglect. In addition, training that
      targets workplace violence was found to be related to enhanced perceptions of
      control.

PMID- 10912502
TI  - Effect of B2m gene disruption on MHC-determined odortypes.
AB  - Major histocompatibility complex (MHC) genes confer individual olfactory identity
      that can be detected with exquisite accuracy by mice. The fact that MHC genes
      themselves generate the characteristic odortype, rather than dedicated odor
      determining genes, was supported in studies of point mutations in H2K and HLA
      transgenic mice, which evinced distinct odor profiles in olfactory assays. In
      this article we provide further evidence for a central role of MHC genes
      themselves in odortype specification by demonstrating that mice that are unable
      to express their genomic class I MHC genes because they lack beta2-microglobulin
      are distinguishable by scent from otherwise identical mice which possess an
      intact B2m gene. This odortype disparity appears at 9-12 days of gestational age,
      the period in which the MHC is first detectable in fetal cells of normal mice.

PMID- 10912503
TI  - Germline repertoire of the immunoglobulin V(H)3 family in rhesus monkeys.
AB  - To facilitate molecular studies of antibody responses in rhesus monkeys (Macaca
      mulatta), we cloned and sequenced germline segments from its largest and most
      diverse immunoglobulin heavy-chain gene family, V(H)3. Using a PCR-based
      approach, we characterized 29 sequences, 20 with open reading frames (ORFs) and 9
      pseudogenes. The leader sequences, introns, exons, and recombination signal
      sequences of M. mulatta V(H)3 gene segments are not strictly identical to those
      of humans, but the mature coding regions demonstrate, on average, greater than
      90% sequence similarity. Although the framework regions are more highly
      conserved, the complementarity-determining regions (CDRs) also show strong
      similarities, and their predicted three-dimensional structures resemble those of
      their human homologues. In one instance, homologous macaque and human CDR1
      sequences were 100% identical at the nucleotide level, and some CDR2s shared
      nucleotide identity as high as 96.5%. However, some rhesus V(H)3 ORFs have
      unusual structural features, including atypical CDR lengths and uncommon amino
      acids at structurally crucial positions. The similarity of rhesus and human V(H)3
      homologues reinforces the notion that humoral immunity in this nonhuman primate
      species is an appropriate system for modeling human antibody responses.

PMID- 10912504
TI  - Sequence and diversity of MHC DQA and DQB genes of the owl monkey Aotus
      nancymaae.
AB  - The New World primate Aotus nancymaae has been recommended by the World Health
      Organization (WHO) as a model for evaluation of malaria vaccine candidates, given
      its susceptibility to experimental infection with the human malaria parasites
      Plasmodium falciparum and Plasmodium vivax. We present here the nucleotide
      sequences of the complete cDNA of MHC-DQA1 and of the polymorphic exon 2 segments
      of MHC-DQB1/DQB2. In a group of three nonrelated animals captured in the wild,
      five alleles of MHC-DQA1 could be identified. They all belong to one lineage,
      namely Aona-DQA1*27. This lineage has not been described in any other New World
      monkey species studied. In a group of 19 unrelated animals, 14 Aona-DQB1 alleles
      could be identified which are grouped into the two lineages Aona-DQB1*22 and Aona
      DQB1*23. These lineages have been described previously in the common marmoset and
      cotton-top tamarin. In addition, two Aona-DQB2 sequences could be identified
      which are highly similar to HLA-DQB2 sequences. Essential amino acid residues
      contributing to MHC DQ peptide binding pockets number 1 and 4 are conserved or
      semi-conserved between HLA-DQ and Aona-DQ molecules, indicating a capacity to
      bind similar peptide repertoires. These results fully support the use of Aotus
      monkeys as an animal model for evaluation of future subunit vaccine candidates.

PMID- 10912505
TI  - Importance of GAD65 peptides and I-Ag7 in the development of insulitis in
      nonobese diabetic mice.
AB  - Insulin-dependent diabetes mellitus (IDDM) develops in nonobese diabetic (NOD)
      mice through the destruction of the B cells in pancreatic Langerhans islets by
      islet autoantigen-specific T cells. The islet autoantigen glutamic acid
      decarboxylase 65 (GAD65) is thought to be a major target autoantigen in IDDM. In
      the present report, we established GAD65-specific T-cell clones using overlapping
      peptides that cover the amino acid sequences of mouse GAD65. T-cell epitopes of
      GAD65 were characterized by proliferation and binding assays using various
      analogue peptides and wild-type or mutant I-Ag7 transfectants. The efficacy of
      the peptide vaccine in IDDM was determined by administering T-cell epitope
      peptides to NOD mice and evaluating the histopathology of their insulitis. We
      obtained two types of T-cell clone, one specific for peptide p316-335 and another
      specific for p531-545 of GAD65. The p531-545 site has already been identified,
      but we report the p316-335 site for the first time. T-cell clones recognized
      those peptides in the wild-type I-Ag7 but not in the mutant I-Ag7 in which the
      serine at position 57 of the beta-chain was replaced by an aspartic acid. Both
      the p316-335 and p531-545 peptides bound weakly to I-Ag7. Some peptides with
      amino acid substitutions had antagonistic activity, and administration of a large
      amount of wild-type peptide reduced the severity of insulitis in NOD mice. Our
      results suggest that peptide vaccine therapy may be useful in autoimmune
      diseases, including IDDM.

PMID- 10912506
TI  - Gene structure of human and mouse NKLAM, a gene associated with cellular
      cytotoxicity.
AB  - A novel gene involved in cytotoxicity, NKLAM [for "natural killer (NK) lytic
      associated molecule"], has recently been identified in human NK cells. Its
      expression correlates with the cytolytic activity of both NK cells and cytotoxic
      T cells (CTLs); treatment of these cells with NKLAM-specific antisense
      oligonucleotides inhibits their cytotoxic function. NKLAM encodes a zinc finger
      protein that resides in NK cytolytic granules. Here, we identified a second human
      NKLAM transcript that differs from the original only at the 3' end, extending the
      open reading frame, and therefore encoding a significantly longer protein (731
      residues compared with 587). The genomic structure of human NKLAM indicates that
      these two isoforms are products of alternative splicing. Both forms of NKLAM
      protein are expressed in NK cells, with the larger protein predominant. Human
      NKLAM cDNA was used to isolate mouse NKLAM from a C57BL/6 spleen cDNA library.
      There is a single NKLAM isoform in the mouse which shares over 89% nucleotide and
      94% amino acid homology with the larger human form of NKLAM. The genomic
      organization of NKLAM is similar in both mouse and human. As with human NKLAM,
      mouse NKLAM mRNA is selectively expressed in CD8+ T cells NK cells, and activated
      peritoneal macrophages and further induced by cytokines that enhance the
      cytotoxic activity of these cells. These results indicate that human and mouse
      NKLAM are highly conserved both structurally and functionally, reinforcing the
      premise that this gene plays an important role in cellular cytotoxicity.

PMID- 10912507
TI  - Mhc class II B gene evolution in East African cichlid fishes.
AB  - A distinctive feature of essential major histocompatibility complex (Mhc) loci is
      their polymorphism characterized by large genetic distances between alleles and
      long persistence times of allelic lineages. Since the lineages often span several
      successive speciations, we investigated the behavior of the Mhc alleles during or
      close to the speciation phase. We sequenced exon 2 of the class II B locus 4 from
      232 East African cichlid fishes representing 32 related species. The divergence
      times of the (sub)species ranged from 6,000 to 8.4 million years. Two types of
      evolutionary analysis were used to elucidate the pattern of exon 2 sequence
      divergence. First, phylogenetic methods were applied to reconstruct the most
      likely evolutionary pathways leading from the last common ancestor of the set to
      the extant sequences, and to assess the probable mechanisms involved in allelic
      diversification. Second, pairwise comparisons of sequences were carried out to
      detect differences seemingly incompatible with origin by nonparallel point
      mutations. The analysis revealed point mutations to be the most important
      mechanism behind allelic divergences, with recombination playing only an
      auxiliary part. Comparison of sequences from related species revealed evidence of
      random allelic (lineage) losses apparently associated with speciation. Sharing of
      identical alleles could be demonstrated between species that diverged 2 million
      years ago. The phylogeny of the exon was incongruent with that of the flanking
      introns, indicating either a high degree of convergent evolution at the peptide
      binding region-encoding sites, or intron homogenization.

PMID- 10912508
TI  - Major histocompatibility complex class II A genes in cichlid fishes:
      identification, expression, linkage relationships, and haplotype variation.
AB  - Two cichlid species, the haplochromine Aulonocara hansbaenschi and the tilapiine
      Oreochromis niloticus, were used to study the major histocompatibility complex
      (Mhc) class II A variation within this group. Multiple class II A sequences were
      recovered from A. hansbaenschi and O. niloticus cDNA libraries and three sequence
      families, DAA, DBA, and DCA, were identified. Sets of O. niloticus haploid embryo
      families were used to determine the linkage relationships of these genes. Two
      independently assorting linkage groups were detected, DAA and DBA/DCA, neither of
      which is linked to the previously described Mhc class I gene cluster. Three DCA
      genes and up to four DBA genes were found to segregate in different haplotypes,
      whereas DAA occurred as a single locus. Four DBA haplotypes, DBA*H1-H4, were
      identified and shown to co-segregate with the previously described class II B
      haplotypes. Four DCA haplotypes, DCA*H1-H4, were found at a distance of 37 cM
      from the DBA/class II B cluster; in one DCA haplotype, DCA*H5, the genes were
      tightly linked to the DBA/class II B clusters. Transcripts of DAA and DBA genes
      were found in O. niloticus hepatopancreas and spleen; transcripts of DCA genes
      were detected in the A. hansbaenschi cDNA library, but not in O. niloticus. These
      findings provide a basis for using class II haplotypes as markers in the study of
      adaptive radiation in the cichlid species flocks of the East African Great Lakes.

PMID- 10912510
TI  - Sequence-specific oligonucleotide probing for MICB alleles reveals associations
      with MICA and HLA-B.

PMID- 10912511
TI  - Allogeneic responses to the class Ib antigen Qa1: limited T-cell receptor Valpha
      but not Vbeta chain usage.

PMID- 10912509
TI  - The sequence of J chain in an amphibian, Rana catesbeiana.

PMID- 10912513
TI  - HLA-Cw*1404: a new HLA-C allele with a hybrid 77Asn-80Asn NK motif.

PMID- 10912512
TI  - A novel Mhc-B-related processed pseudogene in two species of New World primates.

PMID- 10912514
TI  - Growth hormone axis overview--somatomedin hypothesis.
AB  - The possibility that the action of growth hormone (GH) on cartilage is mediated
      by a separate hormonal agent found in serum was suggested by incubation with
      hypophysectomized rat costal cartilage. The stability of this tissue permitted
      long incubations and the measurement of the uptake of 35S-sulfate provided a
      convenient index of growth stimulation. Under the conditions arbitrarily
      selected, normal rat serum, but not serum from hypophysectomized rats, induced a
      great stimulation of 35S uptake. In contrast, GH added directly to cartilage in
      these incubations was virtually inactive. It was suggested that a serum sulfation
      factor, now known as insulin-like growth factor-I (IGF-I), was a mediator of GH
      action. Recently it has been observed that addition of 35S-sulfate after 24 h of
      preincubation with GH permitted the direct effect of GH to be recognized. Other
      observations in intact hypophysectomized rats have established that GH can induce
      the expression of IGF-I in cartilage that acts in an autocrine-paracrine manner.
      The relative importance of the endocrine and autocrine-paracrine routes of IGF-I
      action on the growth of cartilage is in dispute. It is clearly established that
      serum IGF-I exerts a negative feedback on GH secretion by action on the
      hypothalamus and pituitary. Serum IGF-I concentrations reflect GH action in
      postnatal life. Measurement of serum IGF-I is the most-valuable index of GH
      hypersecretion in acromegaly and in conditions of growth impairment. GH receptor
      deficiency leads to a marked decrease in circulating IGF-I. Hypernutrition and
      hyperinsulinism of obesity directly promote hepatic IGF-I release and inhibit GH
      secretion by the pituitary. Differences in hepatic IGF-I synthesis in response to
      GH may contribute to physiological differences in stature.

PMID- 10912515
TI  - The relative importance of endocrine versus autocrine/paracrine insulin-like
      growth factor-I in the regulation of body growth.
AB  - Body growth is regulated by growth hormone (GH) and insulin-like growth factor-I
      (IGF-I). The classical somatomedin hypothesis of this regulation is that most IGF
      I in the blood originates in the liver and that body growth is controlled by the
      concentration of IGF-I in the blood. We have recently abolished IGF-I production
      in the livers of mice by using the Cre/loxP recombination system. These mice
      displayed a more than 75% reduction in serum IGF-I associated with increased
      serum levels of GH. In contrast, they demonstrated a normal postnatal growth,
      indicating that extrahepatic, autocrine/paracrine-acting IGF-I is the main
      determinant of postnatal growth. Thus, the "classical" somatomedin hypothesis
      needs revision. We propose the "dual somatomedin hypothesis" according to which:
      (1) autocrine/paracrine IGF-I is the main determinant of postnatal body growth
      and (2) liver-derived, endocrine-acting, IGF-I exerts negative feedback on GH
      secretion and possibly also exerts other effects on carbohydrate and lipid
      metabolism.

PMID- 10912516
TI  - The growth hormone/insulin-like growth factor-I system: implications for organ
      growth and development.
AB  - Growth hormone (GH) and insulin-like growth factors (IGFs) are essential for
      normal growth and development during embryonic stages as well as postnatally.
      While GH has little effect on these processes prenatally, the IGFs are important
      during these stages. On the other hand the GH-IGF-I axis is important for
      pubertal growth. To determine whether postnatal growth and development are
      dependent on circulating or locally produced IGF-I, we deleted the IGF-I gene in
      the liver using the cre/LoxP system used for tissue-specific gene deletion. These
      animals demonstrated approximately 75%-80% reduction in circulating IGF-I and an
      approximate fourfold increase in circulating GH. Despite the marked reductions in
      circulating IGF-I, growth and development was apparently normal. Thus the
      original somatomedin hypothesis needs to be re-evaluated in the light of these
      new findings.

PMID- 10912517
TI  - Role of the tyrosine kinase JAK2 in signal transduction by growth hormone.
AB  - Chronic renal failure in children results in impaired body growth. This effect is
      so severe in some children that not only does it have a negative impact on their
      self-image, but it also affects their ability to carry out normal day-to-day
      functions. Yet the mechanism by which chronic renal failure causes short stature
      is not well understood. Growth hormone (GH) therapy increases body height in
      prepubertal children, suggesting that a better understanding of how GH promotes
      body growth may lead to better insight into the impaired body growth in chronic
      renal failure and therefore better therapies. This review discusses what is
      currently known about how GH acts at a cellular level. The review discusses how
      GH is known to bind to a membrane-bound receptor and activate a cytoplasmic
      tyrosine kinase called Janus kinase (JAK) 2. The activated JAK2 in turn
      phosphorylates tyrosines within itself and the associated GH receptor, forming
      high-affinity binding sites for a variety of signaling molecules. Examples of
      such signaling molecules include signal transducers and activators of
      transcription (Stats), which regulate the expression of a variety of GH-dependent
      genes, and the adapter protein Shc, which leads to activation of the Ras-Raf-MEK
      MAP kinase pathway. In response to GH, JAK2 is also known to phosphorylate the
      insulin receptor substrates, leading to activation of phosphatidyl inositol 3'
      kinase and most likely other molecules that have been implicated in the
      regulation of metabolism. Finally, the ability of JAK2 to bind and activate the
      presumed adapter protein SH2-B is discussed. SH2-B has been shown to be a potent
      activator of GH-promoted JAK2 activity and downstream signaling events.
      Presumably these and other pathways initiated by GH combine to result in its
      ability to regulate body growth and metabolism.

PMID- 10912518
TI  - Role of insulin receptors and IGF receptors in growth and development.
AB  - Observations in targeted mouse mutants and patients with genetic abnormalities
      grant insight into the various and distinct roles of insulin-like growth factor
      receptors (IGF-Rs) and insulin receptors (IRs) during early development. While
      IGF-1Rs (mediating both IGF-1 and IGF-2 actions) are important for embryonic and
      fetal growth, IRs (mediating IGF-2 rather than insulin action) play a minor role.
      However, it is an oversimplification to conclude that IGF-1Rs mediate growth and
      IRs mediate metabolic responses. Mice lacking both IRs and IGF-1Rs are more
      severely growth retarded than mice lacking either receptor alone. The phenotype
      of combined deficiency of IRs and IGF-1Rs is similar to the phenotype caused by
      the absence of IGF-1 and IGF-2. This provides genetic proof that these two
      receptors account for the entirety of the growth promoting effects of IGF-1 and
      IGF-2. There is little evidence that hybrid insulin/IGF-1 receptors promote
      embryonic growth to a significant degree. The clinical presentation regarding
      severity of growth retardation and metabolic disturbances observed in animal
      models versus in humans may differ greatly and the reasons will be reviewed in
      detail.

PMID- 10912519
TI  - Regulation and role of the acid-labile subunit of the 150-kilodalton insulin-like
      growth factor complex in the mouse.
AB  - After birth, the acid-labile subunit (ALS) associates in the circulation with
      insulin-like growth factor (IGF)-I or -II and with IGF binding protein-3 (IGFBP
      3) to form a 150-kilodalton complex. This association leads to the retention of
      IGFs in the vascular system and promotes their endocrine actions. ALS is
      synthesized almost exclusively in liver, and both hepatic ALS mRNA and
      circulating levels are increased by growth hormone (GH). Three major areas of
      study were pursued to better understand the regulation of ALS synthesis and its
      role in the circulating IGF system. First, the mouse ALS gene was isolated and
      shown to be organized into two exons and a single intron on chromosome 17.
      Second, using transient transfection studies in the rat H4-II-E hepatoma cell
      line and primary rat hepatocytes, the region of the mouse promoter that is
      responsive to GH was mapped to a nine-base pair cis-element resembling a gamma
      interferon-activated sequence. The activation of the mouse ALS gene by GH is
      mediated by the binding of STAT5 isoforms to this sequence. Finally, an ALS
      knockout model was created by inactivating the ALS gene in mouse embryonic stem
      cells. Mice that are homozygous for the mutation grow at a slower rate after
      birth. This growth depression is associated with large decreases in the plasma
      concentrations of both IGF-I and IGFBP-3, indicating the critical role of ALS in
      the regulation of circulating levels of these proteins. Studies of this model
      will lead to a better understanding of the circulating IGF system.

PMID- 10912520
TI  - Overexpression of insulin-like growth factor binding protein-1 in transgenic
      mice.
AB  - Overexpression of insulin-like growth factor-binding protein (IGFBP-1) in
      transgenic mice has provided insight into the physiological role of this binding
      protein in modulating the metabolic and growth-promoting effects of the IGFs.
      IGFBP-1 transgenic mice demonstrate both intrauterine and postnatal growth
      retardation. Organ weight was proportionately reduced relative to body weight in
      most organs, with the exception of the brain, which was disproportionately small
      in transgenic mice. There were no gross neurological manifestations of the
      reduction in brain size. Transgenic mice also demonstrated fasting hyperglycemia,
      impaired glucose tolerance, and modest insulin resistance in skeletal muscle and
      hepatic tissue. From these data, we can conclude that overexpression of IGFBP-1
      results in inhibition of IGF action and in profound impairment of brain
      development, modest inhibition of fetal and postnatal growth, and inhibition of
      the metabolic effects of the IGFs. Increased expression of IGFBP-1 has been
      documented in a variety of situations, such as fetal nutritional deprivation and
      hypoxia, and has been considered to be a marker of metabolic disturbances that
      cause fetal growth retardation. The observations in IGFBP-1 transgenic mice
      suggest expression of IGFBP-1 may itself contribute to the growth retardation and
      impaired fetal brain development.

PMID- 10912521
TI  - Effects of IGFBP-2 overexpression in vitro and in vivo.
AB  - Insulin-like growth factor-binding proteins (IGFBPs) are important modulators of
      IGF actions and may have both stimulatory and inhibitory effects. Expression of
      IGFBP-2 is increased after fasting and in a variety of pathological conditions.
      However, the specific role of IGFBP-2 in growth physiology remains to be
      determined. In this review, we summarize data from in vitro and in vivo models
      suggesting that IGFBP-2 has mainly inhibitory effects on IGF actions. Since the
      growth hormone (GH)/IGF system is involved in a number of pathological
      alterations of the kidney and these changes may--at least in part--be due to
      increased IGF-I, local overexpression of inhibitory IGFBP-2 in the kidney might
      prevent IGF-I-induced lesions. This hypothesis will be tested by crossing GH
      transgenic mice, a common model of glomerulosclerosis, with transgenic mice
      characterized by systemic and renal overexpression of IGFBP-2.

PMID- 10912522
TI  - Effect of chronic renal failure and growth hormone therapy on the insulin-like
      growth factors and their binding proteins.
AB  - Children with chronic-renal failure (CRF) are often growth retarded, and
      abnormalities of the growth hormone (GH)/insulin-like growth factor (IGF) axis in
      CRF may contribute to this poor growth. Despite normal IGF levels in CRF serum,
      IGF bioactivity is low due to excess IGF-binding proteins (IGFBPs) in the 35-kDa
      serum fractions. Levels of IGFBP-1, -2, -4 and -6, and a 29-kDa IGFBP-3 fragment,
      are high in CRF serum, and levels of intact IGFBP- 1 and -2 correlate negatively
      with height. IGFBP-1 levels may be high due to insulin resistance, suggesting
      that the FKHR family of transcription factors may play a role in the
      overexpression of IGFBP-1, and other growth inhibitors, in CRF. GH-treated CRF
      children show catch-up growth that correlates positively with a rise in each
      component of the 150-kDa serum ternary complex (IGF-I or -II/IGFBP-3 or -5/acid
      labile subunit); IGFBP-1, -2 and -6 levels do not rise, but serum IGF bioactivity
      does. Thus, GH increases levels of IGFs and ternary complexes in CRF serum. It is
      likely that increased IGFs contribute to catch-up growth by overcoming the
      inhibitory effects of excess IGFBPs present in the CRF milieu.

PMID- 10912523
TI  - Insulin-like growth factor binding protein (IGFBP) displacers: relevance to the
      treatment of renal disease.
AB  - Chronic renal failure (CRF) results in complex metabolic and hormonal
      derangements, particularly in the GH-IGF-IGFBP axis, which can be manifest in
      children as growth retardation. The decreased glomerular filtration rate (GFR) in
      CRF is associated with increased plasma IGFBP levels, which may have an important
      role in inhibiting the bioavailability of IGF-I. There is a large literature from
      both animal and human studies showing that the administration of IGF-I can affect
      structure and function of normal and compromised kidneys. We propose an
      alternative therapeutic approach: activating bound IGF by administering molecules
      that bind to the IGFBPs. In initial animal studies we used a mutant IGF, an IGF
      displacer, that binds to IGFBPs but not to IGF receptors. In the rat this
      molecule activated the IGF system and produced IGF-like effects in vivo, such as
      increased kidney size, reduced serum creatinine, increased bone growth and
      increased body weight. Novel synthetic peptides have also been discovered which
      bind to specific IGFBPs, and we believe such molecules hold promise as
      therapeutic agents in renal disease.

PMID- 10912524
TI  - Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in
      children with chronic renal failure: relationship to growth and glomerular
      filtration rate. The European Study Group for Nutritional Treatment of Chronic
      Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in
      Chronic Renal Failure.
AB  - Growth retardation in children with chronic renal failure (CRF) is partly due to
      an inhibition of insulin-like growth factor (IGF) activity by an excess of high
      affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the
      serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific,
      recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined
      89 children [age 11.5 (2.8-19.0) years] with CRF [glomerular filtration rate 26.6
      (7.0-67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease
      undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold
      increased in CRF (prepubertal 1080+/-268 ng/ml; pubertal 989+/-299 ng/ml)
      compared to healthy prepubertal controls (265+/-73 ng/ml). In contrast, serum
      IGFBP-5 levels were not significantly increased neither in prepubertal (361+/-120
      ng/ml vs 282+/-75 ng/ml in controls) nor pubertal CRF children (478+/-165 ng/ml
      vs 491+/-80 ng/ml in controls). Immunoblot analysis showed the presence of intact
      as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels
      were inversely correlated with GFR (r=-0.39, P<0.001). In prepubertal children,
      IGFBP-4 levels were inversely correlated with standardized height (r=-0.40;
      P<0.005). In contrast, IGFBP-5 levels were positively correlated both with
      standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45,
      P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43%
      (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive
      correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively
      correlated with IGF-I (r=0.59, P<0.001), IGF-II(r=0.42, P<0.001)and IGFBP-3
      (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=-0.41, P<0.001). In
      summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to
      the degree of renal dysfunction and contributes to the marked increase in IGF
      binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with
      standardized height is consistent with its role as another inhibitor of the
      biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP
      5 is not elevated in CRF serum and circulates mainly as proteolysed fragments.
      The positive correlation of serum IGFBP-5 with growth and its increase during GH
      therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either
      by enhancing IGF activity through better presentation of TGF to its receptor or
      by an IGF-independent effect through activation of a specific, recently described
      putative IGFBP-5-receptor.

PMID- 10912525
TI  - Bone morphogenetic proteins and skeletal development: the kidney-bone connection.
AB  - The bone morphogenetic proteins (BMPs) are a family of pleiotropic morphogens
      isolated and cloned from the demineralized extracellular matrix of bone. BMPs and
      related cartilage-derived morphogenetic proteins (CDMPs) initiate, promote and
      maintain bone and cartilage. The pleiotropic effects of BMPs are based on
      concentration-dependent thresholds. Targeted disruption of gene action by
      homologous recombination has demonstrated the role of BMP 7 in kidney, eye and
      skeletal development. BMP 7 is critical for kidney tubulogenesis, retinal
      pigmented epithelium differentiation and skeletal pattern. BMP 7 is also
      synthesized by the kidney and is detectable in serum; hence BMP 7 is both an
      autocrine and endocrine morphogen. It is likely renal BMP 7 may influence
      skeletal development and growth in children although there may be sources of
      other BMPs with skeletogenic actions. In conclusion, we are beginning to unravel
      the mysteries of kidney-bone connection with special reference to pediatric
      nephrology.

PMID- 10912526
TI  - Chondromodulin-I as a novel cartilage-specific growth-modulating factor.
AB  - Cartilage is unique among mesenchymal tissues in that it is resistant to vascular
      invasion due to an intrinsic angiogenesis inhibitor. Chondromodulin-I (ChM-I), a
      25-kilodalton glycoprotein purified from bovine epiphyseal cartilage on the basis
      of growth-promoting activity for chondrocytes, was recently identified as an
      angiogenesis inhibitor. Human ChM-I cDNA revealed that the mature protein
      consists of 120 amino acids and is coded as the C-terminal part of a larger
      transmembrane precursor. Expression of ChM-I cDNA in CHO cells indicated that
      mature ChM-I molecules were secreted from the cells after post-translational
      modifications and cleavage from the precursor protein at the predicted processing
      site. ChM-I stimulated growth and colony formation of cultured chondrocytes, but
      inhibited angiogenesis in vitro and in vivo. In situ hybridization and
      immunohistochemistry revealed that ChM-I is specifically expressed in the
      avascular zone of cartilage in developing bone, but not present in the late
      hypertrophic and calcified zones that allow vascular invasion. ChM-I actually
      inhibited vascular invasion into cartilage that was ectopically induced by
      demineralized bone matrix in nude mice, leading to the suppression of replacement
      of cartilage by bone in vivo. These results suggest that ChM-I participates in
      the angiogenic switching of cartilage, and that the withdrawal of its expression
      allows capillary in-growth, which triggers the replacement of cartilage by bone
      during endochondral bone development.

PMID- 10912527
TI  - Role of parathyroid hormone-related peptide and Indian hedgehog in skeletal
      development.
AB  - Parathyroid hormone-related peptide (PTHrP), which frequently causes the humoral
      hypercalcemia of malignancy syndrome, is an autocrine/paracrine regulator of
      chondrocyte proliferation and differentiation that acts through the PTH/PTHrP
      receptor (PTH1R). PTHrP is generated in response to Indian hedgehog (Ihh), which
      mediates its actions through the membrane receptor patched, but interacts also
      with hedgehog-interacting protein (Hip). Mice lacking PTHrP show accelerated
      chondrocyte differentiation, and thus premature ossification of those bones that
      are formed through an endochondral process, and similar but more-severe
      abnormalities are observed in PTH1R-ablated animals. The mirror image of these
      skeletal findings, i.e., a severe delay in chondrocyte differentiation and
      endochondral ossification, is observed in transgenic mice that overexpress PTHrP
      under the control of the alpha1(II) procollagen promoter. Severe abnormalities in
      chondrocyte proliferation and differentiation are also observed in two genetic
      disorders in humans that are most likely caused by mutations in the PTH1R.
      Heterozygous PTH1R mutations that lead to constitutively activity were identified
      in Jansen metaphyseal chondrodysplasia, and homozygous or compound heterozygous
      mutations that lead to less-active or completely inactive receptors were
      identified in patients with Blomstrand lethal chondrodysplasia. Based on the
      growth plate abnormalities observed in these human disorders and in mice with
      abnormal expression of either PTHrP or the PTH1R, it appears plausible that
      impaired expression of PTHrP and/or its receptor contributes to the growth
      abnormalities in children with end-stage renal disease. In fact, mild-to-moderate
      renal failure leads in animals to a reduction in PTH1R expression in growth
      plates and impaired growth, but it remains uncertain whether this contributes to
      altered chondrocyte growth and differentiation.

PMID- 10912528
TI  - Suppression of growth plate chondrocyte proliferation by corticosteroids.
AB  - Growth depression is a side effect of high-dose glucocorticoid therapy in
      childhood. It is partially mediated by alterations of the somatotropic hormone
      axis and partially by direct local effects on growth plate chondrocytes. The
      mechanisms of interaction of corticosteroids and somatotropic and calciotropic
      hormones at the cellular level were recently investigated in more detail, using
      experimental models of primary cultures of growth plate chondrocytes. In
      proliferative chondrocytes, growth hormone (GH) and the calciotropic hormones
      parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D [1alpha,25(OH)2D3] increase
      cell proliferation via stimulation of paracrine insulin-like growth factor-I (IGF
      I) secretion. Corticosteroids decreased GH, and PTH or 1alpha,25(OH)2D3
      stimulated cell growth in a dose-dependent manner. Corticosteroids in high doses
      reduced the expression of the GH receptor and type 1 IGF receptor. But the main
      antiproliferative molecular effect of corticosteroid was the reduction in basal
      and hormone-stimulated IGF-I secretion. The in vitro results are in accordance
      with the observation in animal experiments and in children treated with
      corticosteroids, demonstrating that the growth-depressing effect of
      corticosteroids can be compensated for by supraphysiological doses of GH or IGF
      I.

PMID- 10912529
TI  - Catch-up growth: possible mechanisms.
AB  - Many systemic diseases impair linear growth. If remission occurs, growth will
      often accelerate beyond the normal rate for age, a phenomenon termed "catch-up
      growth." As a result, final height is improved, although this recovery of adult
      stature is frequently incomplete. Two principal models have been proposed to
      explain catch-up growth. The first model postulates a central nervous system
      mechanism that compares actual body size with an age-appropriate set-point and
      then adjusts growth rate accordingly. However, there is recent evidence that
      growth inhibition in a single growth plate is followed by local catch-up growth,
      a finding not readily explained by the neuroendocrine model. Thus, a new model
      has been proposed that places the mechanism within the growth plate itself.
      According to this model, growth-inhibiting conditions decrease proliferation of
      growth plate stem cells, thus conserving their proliferative potential.
      Additional research is needed to determine whether the mechanisms governing catch
      up growth are local, systemic, or both.

PMID- 10912530
TI  - Human 25-hydroxyvitamin D-1alpha-hydroxylase: cloning, mutations, and gene
      expression.
AB  - The rate-limiting, hormonally regulated step in the bioactivation of vitamin D is
      the 1alpha-hydroxylation of 25-hydroxyvitamin D, which occurs in the kidney and
      other tissues and is catalyzed by the mitochondrial cytochrome P450 enzyme,
      P450c1alpha. After many years of effort, the cDNA and gene encoding this enzyme
      were cloned from mouse, rat, and human tissue in late 1997. The human gene
      encoding the 1alpha-hydroxylase is 5 kb in length, located on chromosome 12, and
      comprises nine exons and eight introns; its intron/exon organization is very
      similar to that of the other four mitochondrial P450 enzymes cloned to date.
      Mutations in P450c1alpha cause 1alpha-hydroxylase deficiency, also known as
      vitamin D-dependent rickets type 1, a rare autosomal recessive disease
      characterized by rickets and impaired growth due to failure of renal synthesis of
      1,25(OH)2D. To date, 31 patients have been studied and 20 distinct mutations in
      the gene identified, including 13 mis-sense mutations, none of which encode a
      protein with significant enzyme activity. Recent studies in animals demonstrate
      that regulation of P450c1alpha gene expression by parathyroid hormone (PTH), low
      calcium diet, low phosphorus diet, and 1,25(OH)2D occurs at the level of its
      mRNA. Transcriptional activity of the mouse and human P450c1alpha gene promoters
      can be stimulated by PTH, cAMP, and forskolin and suppressed by 1,25(OH)2D.

PMID- 10912531
TI  - Molecular mechanisms of secondary hyperparathyroidism.
AB  - Secondary hyperparathyroidism is a frequent complication of chronic renal failure
      (CRF) and a major factor in the pathogenesis of renal osteodystrophy. A high
      serum phosphate, decreased levels of serum 1,25(OH)2D3 and the subsequently low
      serum calcium are the major metabolic abnormalities in CRF, which lead to the
      secondary hyperparathyroidism. At the level of parathyroid hormone (PTH)
      secretion there is insensitivity to the ambient serum calcium. PTH mRNA levels
      are increased by a post-transcriptional mechanism that involves the binding of PT
      cytosolic proteins to the PTH mRNA 3'-untranslated region (UTR). In a dietary
      model of secondary hyperparathyroidism due to hypocalcemia there is increased
      binding of parathyroid proteins to the 3'-UTR and decreased degradation as
      determined by an in vitro degradation assay. Changes in serum phosphate also
      dramatically regulate PTH mRNA stability. There is also regulation at the level
      of PT cell proliferation. PT cell proliferation is increased by experimental
      hypocalcemia or hyperphosphatemia and decreased by hypophosphatemia and
      administered 1,25(OH)2D3. The understanding of the molecular mechanisms involved
      in the genesis of secondary hyperparathyroidism will allow the design of new
      effective strategies in the management of this troubling condition.

PMID- 10912533
TI  - Pathophysiology of renal osteodystrophy.

PMID- 10912532
TI  - Molecular bone morphometry.
AB  - Quantitative histomorphometric assessment of bone biopsies represents a powerful
      and informative method for the study of metabolic bone diseases. It is the gold
      standard against which the noninvasive "diagnostic" markers of bone metabolism as
      well as newly available therapeutic modalities are tested. With the rapid
      progress in technology of molecular biology, identification of systemic and local
      biomolecules known to regulate bone metabolism can now be achieved. The study of
      localization, levels of expression, and synthesis of these factors in bone and
      its microenvironment is possible through applications of in situ hybridization
      histochemistry (ISHH) and immunohistochemistry (IHC). Application of ISHH allows
      study of specific mRNA expression. IHC determines the presence and distribution
      of target protein in cells. These two methodologies provide the link between the
      cellular processes of mRNA transcription and translation to the working protein.
      Combining the established bone histomorphometric techniques with ISHH and IHC
      elevates the study of bone to new heights, i.e., cellular and molecular
      mechanistic issues can now be studied.

PMID- 10912534
TI  - Implications of intermittent calcitriol therapy on growth and secondary
      hyperparathyroidism.
AB  - Secondary hyperparathyroidism is the most common skeletal lesion in pediatric
      patients undergoing maintenance dialysis. The present review summarizes a
      prospective randomized study that evaluated the biochemical and skeletal
      responses to intermittent calcitriol therapy in 33 pediatric patients on
      peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of
      intermittent calcitriol therapy on linear growth was evaluated in 16 of 33
      patients who had completed the clinical trial. Serum parathyroid hormone levels
      decreased by 62% from 648+/-125 pg/ml in patients treated with intermittent
      intraperitoneal (IP) calcitriol, and values remained unchanged from pre-treatment
      levels of 670+/-97 pg/ml with oral calcitriol therapy. Overall serum total and
      ionized calcium levels were higher in patients treated with IP calcitriol during
      the study. In contrast to these biochemical findings, the skeletal lesions of
      secondary hyperparathyroidism improved after 12 months of treatment in both
      groups and adynamic bone occurred in 33% of the patients. Z-scores for height
      decreased from -1.80 /-0.3 to -2.00+/-0.3, P<0.01, after 12 months of
      intermittent calcitriol therapy. Such findings suggest that an intermittent
      schedule of calcitriol administration adversely affects chondrocyte activity
      within epiphyseal cartilage in pre-pubertal children with end-stage renal
      disease.

PMID- 10912535
TI  - Modulation of endochondral bone formation: roles of growth hormone, 1,25
      dihydroxyvitamin D and hyperparathyroidism.
AB  - Impairment of linear growth occurs invariably in children with chronic renal
      failure. Recombinant human growth hormone and 1,25-dihydroxyvitamin D
      (calcitriol) are widely utilized to improve linear growth in children. Large
      doses of calcitriol, however, have been shown to suppress chondrocyte
      proliferation and may lead to the development of adynamic bone. Substantial
      reductions of growth have been shown in children with chronic renal failure
      treated with intermittent calcitriol therapy. These findings suggest that
      calcitriol can modify chondrocyte proliferation and/or differentiation in
      epiphyseal growth plate cartilage and may counteract the effects of growth
      hormone therapy in increasing linear growth in children with chronic renal
      failure. Parathyroid hormone related peptide (PTHrP) and its receptor (PTH/PTHrP
      receptor) play critical roles in regulating chondrocyte differentiation in the
      growth plate. The expression of PTH/PTHrP receptor mRNA is downregulated in
      animals with chronic renal failure and advanced secondary hyperparathyroidism;
      calcitriol and growth hormone therapy may modify the expression of PTH/PTHrP
      receptor. This article summarizes the separate and combined effects of growth
      hormone and calcitriol on endochondral bone formation in chronic renal failure
      and secondary hyperparathyroidism.

PMID- 10912536
TI  - Mechanism of transplantation-associated bone loss.
AB  - Successful renal transplantation is associated with abnormalities of function of
      the musculoskeletal system. Some of these problems result from incomplete
      resolution of abnormalities of mineral metabolism associated with end-stage renal
      disease, such as persistent hyperparathyroidism, hypercalcemia and decreased
      vitamin D. However, it is now appreciated that skeletal abnormalities, especially
      osteopenia with subsequent fractures, develop following transplantation. Most of
      the new disorders of bone and mineral metabolism are secondary to the
      immunosuppression required to prevent rejection. Glucocorticoids can not only
      induce osteonecrosis, but also increase the risk for fractures by decreasing
      cancellous bone mass and synthesis of bone matrix, and dampen the linear growth
      response in pediatric recipients. Other immunosuppressive agents, especially the
      calcineurin-phosphate inhibitors, independently exert a negative effect on bone.
      Future investigation is required to develop a better understanding of the
      pathophysiologic mechanisms involved in post-transplant bone disease in order to
      develop rational approaches for prevention and treatment.

PMID- 10912537
TI  - Bone mineral density in children after renal transplantation.
AB  - A successful kidney transplantation (Tx) offers good quality of life for children
      suffering from chronic renal failure. However, some metabolic abnormalities may
      not be corrected and may persist after Tx despite good graft function. Post-Tx
      bone disease seems to be a universal finding in adult Tx recipients, and is most
      probably related to steroids. Reports on bone mineral density (BMD) in children
      after renal Tx are not uniform. Recent studies suggest that BMD is normal when
      corrected for height. However, longitudinal studies show a transient decrease in
      BMD in the early post-Tx period. These controversial results raise the issue of
      the correct interpretation of dual-energy X-ray absorptiometry in children with
      stunted growth. Etiopathogenetic factors of the decreased BMD, preventive and
      therapeutic measures are discussed. In conclusion, the results of dual energy X
      ray absorptiometry should be interpreted with caution, especially in children
      with disturbed growth.

PMID- 10912538
TI  - Daily but not pulse calcitriol therapy improves growth in experimental uremia.
AB  - Calcitriol (C) pulse therapy is widely used to suppress secondary renal
      hyperparathyroidism. However, high C serum concentrations may have an
      antiproliferative effect on growth cartilage cells and may suppress growth rate.
      The study was designed to evaluate whether daily C and pulse C therapy have
      differential effects on growth in uremic rats. Female Sprague-Dawley rats (150 g,
      n=5-10 per group) underwent two-stage subtotal nephrectomy (U). The duration of
      uremia was 14-18 days. The animals were fed a standard diet or a diet with a low
      calcium content. Rats on a low-calcium diet were randomized for recombinant human
      growth hormone (rhGH) treatment (2.5 IU/kg per day) or solvent. C was injected
      subcutaneous twice daily (15 pmol/day) or intraperitoneal (105 pmol) twice per
      week. Weight gain and length gain was determined weekly. After sacrifice, total
      body calcium was determined by total body neutron activation analysis. Bone
      micromorphometric analysis of third lumbar vertebra and double staining with
      tetracycline for determination of mineralization rate were performed. Whereas
      daily C significantly increased total body length gain within 2 weeks, pulse C
      did not (U solvent 4.0+/-0.3 cm, UC bolus 4.3+/-0.4 cm, UC daily 5.3+/-0.3 cm,
      P<0.05). A low-calcium diet reduced and rhGH increased basal length gain and
      weight gain; regardless of these preconditions, daily but not bolus C increased
      length gain significantly. C both daily and in bolus form reduced bone osteoid
      content, but daily C improved mineral apposition rate more than C bolus. Total
      body calcium corrected for body weight decreased with a low-calcium diet, was
      lowest with concomitant rhGH treatment, and was not improved by C. In conclusion,
      daily but not bolus C treatment improves growth in uremic rats.

PMID- 10912539
TI  - Calcitriol pulse therapy is not more effective than daily calcitriol therapy in
      controlling secondary hyperparathyroidism in children with chronic renal failure.
      European Study Group on Vitamin D in Children with Renal Failure.
AB  - Calcitriol oral pulse therapy has been suggested as the treatment of choice for
      secondary hyperparathyroidism, but its efficacy and safety are still under
      discussion. The present randomized multicenter study compares the effect of an 8
      week course of daily versus intermittent (twice weekly) calcitriol therapy on
      parathyroid hormone (PTH) suppression in 59 children (mean age 8.4+/-4.7 years)
      with chronic renal insufficiency (mean Ccr 22.4+/-11.6 ml/min per 1.73 m2) and
      secondary hyperparathyroidism. After a 3-week washout period, the patients were
      randomly assigned to treatment with daily oral calcitriol (10 ng/kg per day) or
      intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose
      was not changed throughout the study period of 8 weeks. At start of the study,
      the median intact PTH (iPTH) level was 485 pg/ml (range 83-2032) in the daily
      group (n=29) and 315 pg/ml (range 93-1638) in the intermittent group (n=30).
      After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63
      1614) and 218 pg/ml (range 2-1785) (ns). The mean iPTH decrease from baseline was
      19.2+/-57.8% and 13.7+/-46.7% respectively (not significant). Calcitriol reduced
      the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the
      intermittent group. One episode of hypercalcemia (>11.5 mg/dl) was observed in
      both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed
      in the daily group. It is concluded that oral calcitriol pulse therapy does not
      control secondary hyperparathyroidism more effectively than the daily
      administration of calcitriol in children with chronic renal failure prior to
      dialysis.

PMID- 10912540
TI  - Analysis of muscle strength and bone structure in children with renal disease.
AB  - Bone structure and muscular strength of 30 children with renal disease were
      investigated by peripheral computed tomography and grip strength. Sixteen
      children suffered from nephrotic syndrome (NS) and had previously been treated
      with corticosteroids. Fourteen children suffered from chronic renal failure (CRF)
      ranging from mild renal failure to end-stage renal disease. Six children had
      received kidney transplants and corticosteroids for immunosuppression. There was
      a significant decrease in grip strength of children with NS (SD -0.91+/-1.5;
      P=0.042) and children with CRF (SD -1.38+/-1.4; P<0.001) compared with normal
      children. Furthermore, there was a significant correlation between cortical area
      and grip strength in all children with renal disease (r=0.92; P<0.0001).
      Trabecular bone mineral density did not correlate well with grip strength. These
      findings resemble results found in healthy children. Trabecular bone mineral
      density was significantly elevated in children with CRF compared with normal
      children (SD 1.14+/-1.4; P=0.008). Grip strength as a marker of muscle mass and
      cortical area as a marker of bone strength correlate well in children with renal
      disease, similar to the correlation in healthy children. Grip strength is
      significantly lower in children with NS and CRF compared with normal children.
      These data suggest that muscular impairment could be involved in renal
      osteopathy.

PMID- 10912541
TI  - Assessment of body composition in children with chronic renal failure.
AB  - In children with chronic renal failure treated conservatively by dialysis or by
      transplantation, various alterations of the nutritional, metabolic and fluid
      homeostasis may occur that may critically affect the patients' acute and chronic
      well-being. In the past, the assessment of body composition in children was
      hampered by insufficient precision, standardization and/or availability of
      appropriate anthropometric tools. Recently, there have been several
      methodological advances that may facilitate close and precise monitoring of body
      composition in this population. Specifically, the use of body mass index (BMI)
      data in children has become possible by the introduction of pediatric reference
      values processed for the calculation of standard deviation scores accounting for
      the skewed distribution of BMI. Skewness-adapted reference data have also been
      provided for percentage fat mass as assessed by multisite skinfold measurements.
      In addition, bioelectrical impedance analysis has been validated in healthy
      children as well as in pediatric dialysis and renal transplant populations. This
      novel auxological technique provides a highly reproducible, non-invasive and
      inexpensive way of assessing changes in total body water content in dialysed
      patients, as well as changes in fat and fat-free mass prior to dialysis and after
      renal transplantation.

PMID- 10912542
TI  - The impact of recombinant human growth hormone treatment on final adult height.
AB  - There are limited data addressing the issue of final adult height following
      treatment with recombinant human growth hormone (rhGH). Utilizing the
      chronological age of 18 years as the arbitrary age of final adult height for
      children with chronic renal insufficiency, all patients enrolled in the North
      American Pediatric Renal Transplant Cooperative Study prior to January 1999, and
      who had at least one follow-up visit at age 18 years or older, were evaluated.
      When comparing the final adult height in those patients receiving prior rhGH with
      a group not receiving rhGH, the delta height standard deviation score was greater
      in the rhGH treatment group.

PMID- 10912544
TI  - Growth and renal function after steroid-free tacrolimus-based immunosuppression
      in children with renal transplants.
AB  - Steroid withdrawal after renal transplantation and cyclosporine-based
      immunosuppression enhances growth in children, but this practice is not widely
      employed because of a 50%-60% rate of rejection, graft dysfunction, or graft
      loss. The current study evaluates growth and renal function after withdrawal and
      discontinuation of steroids within 1 year of transplantation in 52 children
      receiving tacrolimus (FK-506)-based immunosuppression. Height Z-score, weight-for
      height index (WHI), and body mass index (BMI), as well as graft loss and
      calculated creatinine clearance as a measure of glomerular filtration rate (GFR),
      were assessed. Children were divided into three groups according to age at
      transplantation: group I, 16 children aged 0-5 years; group II, 17 children aged
      6-12 years; group III, 19 children aged 13-16 years. Significant and sustained
      improvement in height occurred in groups I and III, with Z-scores increasing by
      1.51 and 1.57 standard deviations at 3 years after transplantation compared with
      the Z-score at transplantation (P<0.02). Mean WHI values remained near 100% in
      groups I and III, and significantly increased above 100% only in group II at 2
      years after transplantation. Although actual BMI scores improved significantly in
      groups II and III at both 2 and 3 years post transplantation (P<0.05), when BMI
      scores were adjusted for height age, none of these groups had values >95%
      denoting obesity. Failure of steroid withdrawal, defined as reinstitution of
      steroids, graft dysfunction, or graft loss, occurred in 9 of 68 (13%) children
      who underwent steroid withdrawal at any time after transplantation, and resulted
      in graft dysfunction or graft loss in 5 (7%). Over a 3-year period, rates of
      renal dysfunction, as manifested by >50% rise in the serum creatinine level above
      baseline, or graft loss were lower in these 68 children compared with 8 children
      who never had steroid withdrawal (P<0.05). Mean GFR at 3 years after
      transplantation ranged from 96 to 102 ml/min per 1.73 m2 in all three steroid
      withdrawal groups, and remained stable during the 3 years of follow-up. These
      data indicate that steroid withdrawal enables normalization of growth without
      obesity, and without imposing an excessive risk for graft dysfunction or graft
      loss.

PMID- 10912543
TI  - Effect of deflazacort versus methylprednisone on growth, body composition, lipid
      profile, and bone mass after renal transplantation. The Deflazacort Study Group.
AB  - Kidney function, growth velocity, weight/height ratio, body composition, lipid
      profile, and bone mass were studied in a randomized, multicenter trial of
      deflazacort versus methylprednisone in 27 prepubertal patients with kidney
      transplantation. Methylprednisone (0.20+/-0.03) was replaced by deflazacort (13
      patients, 0.30+/-0.03 mg/kg per day). After 12 months, creatinine clearance
      decreased significantly only during methylprednisone therapy. Growth velocity
      increased only in patients treated with deflazacort from 3.3+/-0.6 to 5.6+/-0.5
      cm/year. Serum levels of several components of the insulin-like growth factor
      axis did not change. Weight/height ratio was increased in methylprednisone
      treated patients (P<0.05) and decreased in deflazacort-treated patients
      (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and
      serum leptin increased only in methylprednisone-treated patients (P<0.025). Total
      cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone
      treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein
      cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11%
      (P<0.005) in deflazacort-treated patients. Total skeleton and lumbar spine bone
      mineral density decreased in both groups, but at 1 year methylprednisone-treated
      patients had lost 50% more bone. Bone mineral content decreased only in
      methylprednisone-treated patients (P<0.01). Our data suggest that substituting
      deflazacort for maintenance methylprednisone might prevent height loss, excessive
      bone loss, and fat accumulation; and leads to an improvement in the lipoproteins
      of these children.

PMID- 10912545
TI  - Changes in body composition of children with chronic renal failure on growth
      hormone.
AB  - Body composition is altered in children with chronic renal failure (CRF) and
      contributes to the significant growth failure seen in these children. Recombinant
      human growth hormone (rhGH) has been used in the past several years to improve
      the somatic growth of children with CRF. To determine if the growth achieved in
      these children occurs concomitantly with body compositional changes, seven
      prepubertal (n=6) and pubertal (n=1) children with chronic renal insufficiency
      (n=4) and end-stage renal disease (n=3) underwent measurements of total body fat
      (FM), fat free mass (FFM), bone mineral density (BMD), total bone mineral mass
      (TBBM), total body water (TBW), and total body potassium (TBK) before and 6
      months after initiation of subcutaneous recombinant human growth hormone (rhGH)
      at 0.35 mg/kg per week. The techniques used included dual-energy X-ray
      absorptiometry (for measurement of FM, BMD, and TBBM), total body potassium
      counting (for measurement of TBK), and deuterated water for assessment of TBW.
      Significant increases in both height and weight were seen following 6 months of
      rhGH therapy. These increases were accompanied by significant reductions in FM
      (4.4+/-1.4 kg vs. 3.6+/-1.2 kg, P=0.002) and percentage fat (18.6+/-3.9% vs.
      14.5+/-3.4%, P=0.04), while FFM (17.9+/-3.0 kg vs. 20.7+/-3.6 kg, P=0.04)
      increased significantly as did TBBM (776+/-171 g vs. 844+/-177 g, P=0.001).
      Increases in TBK, a measure of body cell mass, were also seen. No difference in
      total BMD was observed. Thus, growth in CRF is occurring with repletion of the
      FFM and TBBM compartments. Despite these improvements, no change was observed in
      the body mass index (BMI). Measurement of BMI alone does not define the
      compartmental catabolic losses in FFM.

PMID- 10912547
TI  - Abolishing disease: the best way to tackle inequality.

PMID- 10912546
TI  - Long-term effects of growth hormone treatment on growth and puberty in patients
      with chronic renal insufficiency.
AB  - Several prospective trials have shown that recombinant human growth hormone (GH)
      accelerates growth significantly during the first years of therapy, but the
      effects of long-term GH therapy with regard to long-term growth response and
      safety have not yet been established. Forty-five Dutch prepubertal children [28
      boys, 17 girls, mean (SD) age 7.8 (3.4) years] with chronic renal insufficiency
      (CRI) and severe growth retardation started GH therapy between 1988 and 1991
      within one of the randomized Dutch trials. Long-term GH therapy, in this study a
      maximum of 8 years, resulted in a sustained and significant improvement of height
      standard deviation score (SDS) compared with baseline values (P<0.001). The mean
      height SDS reached the lower end (-2 SDS) of the normal growth chart after 3
      years of GH therapy. During the following years the mean height SDS gradually
      increased, thereby approaching the mean target height SDS after 6 years of GH
      therapy. Three factors were significantly associated with the height SDS after 4
      years of GH therapy: height SDS at the start (+) of therapy, age at the start of
      therapy (-), and the duration of dialysis treatment (-). Bone maturation did not
      accelerate during long-term GH therapy. Children on a conservative regimen at the
      start of GH therapy had no accelerated deterioration of renal function during 6
      years of GH therapy. The average daily GH dose administered over the years had no
      significant influence on the glomerular filtration rate after 4 years. GH therapy
      had no adverse effects or significant effect on parathyroid hormone
      concentration, nor were there any radiological signs of renal osteodystrophy.
      Puberty started at a median age, within the normal range, of 12.4 years in boys
      and 12.0 years in girls, respectively. Long-term GH therapy leads to a sustained
      improvement in height SDS in children with growth retardation secondary to CRI,
      resulting in a normalization of height in accordance with their target height
      SDS, without evidence of deleterious effects on renal function or bone
      maturation. A GH dosage of 4 IU/m2 per day appears efficient and safe. Our long
      term data show that final height will be within the normal target height range
      when GH therapy is continued for many years.

PMID- 10912548
TI  - Help--we need a helpline! A public health audit case study.
AB  - Multi-disciplinary public health audit involving whole departments is often
      perceived as difficult to carry out in areas other than the annual report of the
      Director of Public Health. This paper describes the audit of an emergency
      telephone helpline set up during a meningococcal disease outbreak and provides
      standards that could be applied to any emergency helpline set up in response to
      issues of public health concern.

PMID- 10912549
TI  - Incomplete and inaccurate death certification--the impact on research.
AB  - BACKGROUND: The objectives of this study were (1) to investigate the extent of
      erroneous and/or omitted information on death certificates of patients-implanted
      with Bjork-Shiley Convexo-Concave (BSCC) heart valves; (2) to determine whether
      this information could be associated with a possible under-reporting of acute
      mechanical failure of this valve. METHODS: A review was carried out of death
      certificates and clinical notes for patients implanted in the United Kingdom with
      BSCC valves. This was a multicentre study (38 hospitals) based at the
      Cardiothoracic Department, NHLI, Imperial College School of Medicine at
      Hammersmith Hospital, London. The subjects were 478 patients implanted with a
      BSCC valve between 1979 and 1986 who died in the following years: 1984, 1987,
      1990, 1993 and 1996. The main outcome measures were: (1) percentage of death
      certificates that record the presence of a valve prosthesis; (2) percentage of
      death certificates that record the presence of a valve prosthesis for patients
      who had a post mortem; (3) percentage of death certificates that record
      inaccurate or incomplete information related to the surgery; (4) percentage of
      death certificates that do not record a post mortem where one is known to have
      been performed. RESULTS: Twenty-one per cent (101/478) of the total number of
      death certificates record the presence of the valve prosthesis. Thirty-five per
      cent (43/123) of the death certificates for patients who had a post mortem record
      the presence of a valve prosthesis. Six per cent (30/478) of death certificates
      report inaccurate information related to the valve surgery. Twenty-five per cent
      (118/478) of the total number of death certificates recorded a single cause of
      death. Twenty-three per cent (110/478) of all death certificates reviewed
      recorded only the mode of dying. Eight per cent (10/123) of the total number of
      death certificates for patients who had a post mortem did not record a post
      mortem. CONCLUSIONS: The relatively high number of death certificates that do not
      record the presence of a valve prosthesis and the observed under-reporting of
      post mortems may lead to inaccurate reporting of the number of BSCC valves that
      fail. Previous recommendations to improve accuracy in death certification appear
      to have gone unheeded, and changes in the way certificates are completed for
      patients with implanted cardiac devices should be considered.

PMID- 10912550
TI  - Evaluation of a community-based intervention to increase breastfeeding
      prevalence.
AB  - BACKGROUND: The aim of the study was to determine whether peer counselling in the
      antenatal and post-natal period would increase the prevalence and duration of
      breastfeeding among low-income women in Glasgow. METHODS: The study was designed
      as a quasi-experimental evaluation of a community-based breastfeeding promotion
      programme. The intervention comprised peer counselling of pregnant women, support
      of breastfeeding mothers and local awareness-raising activities. The study
      subjects were all women attending the antenatal booking clinic resident in either
      the intervention or control area. Data were collected by means of four self
      completion questionnaires, two administered antenatally and two post-natally. The
      proportions intending to breastfeed or breastfeeding in the intervention and
      control groups were compared at each assessment and over time. RESULTS: Of the
      995 women enrolled in the study, data were available for analysis on 919 (92 per
      cent) to 6 weeks postnatally. At booking, 18 per cent of the intervention group
      and 21 per cent of the control group stated an intention to breastfeed. At
      delivery, the proportions initiating breastfeeding were 23 per cent of the
      intervention subjects and 20 per cent of the controls, and by 6 weeks post
      natally, the proportion providing any breast milk had declined to 10 per cent of
      the intervention group and 8 per cent of the control group. Using multivariate
      analysis to adjust for factors (such as socio-economic status) known to influence
      breastfeeding, the breastfeeding prevalence was significantly higher in the
      intervention group relative to the controls at delivery [odds ratio (OR) 2.0; 95
      per cent confidence interval (CI) 1.2-3.1, p = 0.006]. By 6 weeks post-natally
      the difference between the two groups was not statistically significant (OR 1.8;
      95 per cent CI 1.0-3.4, p=0.07). CONCLUSIONS: As the impact of the intervention
      was not sustained even for the modest duration of 6 weeks postnatally, it would
      be premature to justify widespread use of peer support programmes to increase the
      prevalence of breastfeeding in socially disadvantaged communities.

PMID- 10912551
TI  - Identifying industrial sites with potential for residential exposure to asbestos.
AB  - BACKGROUND: Non-occupational exposure to asbestos has been of increasing
      interest, but residential exposure to asbestos often focuses on a few high
      profile asbestos users. This study aimed to identify industrial sites producing
      asbestos goods in a given area and time period. METHODS: A search of trade
      directories was carried out for industrial sites in West Yorkshire, England,
      where asbestos may have been used this century. RESULTS: A large number of
      factories with potential for residential exposure were found. A total of 269
      factories in West Yorkshire used asbestos between 1900 and 1979, many for short
      periods only. CONCLUSIONS: Identification of potential sources of residential
      exposure to asbestos would have greatly underestimated their number if either
      only high-profile users or existing official listings had been used. Any
      consideration of asbestos use should aim to identify all users, not just the high
      profile manufacturers.

PMID- 10912552
TI  - Patient satisfaction with out-of-hours services; how do GP co-operatives compare
      with deputizing and practice-based arrangements?
AB  - BACKGROUND: Although the rapid growth in general practitioner (GP) co-operatives
      has met with GP satisfaction, little is known about patient satisfaction. This
      study compares patient satisfaction with co-operative, GP practice-based and
      deputizing arrangements within one geographical area 15 months after a co
      operative had become established; and with telephone, primary care centre and
      home consultations within the co-operative. METHODS: A validated postal
      questionnaire survey of weighted samples of patients making contact with the co
      operative, practice-based and deputizing arrangements was undertaken. RESULTS: A
      total of 1,823 (53.2 per cent) patients responded. There were no significant
      differences between organizations in terms of overall satisfaction, but patients
      using practice-based arrangements were significantly more satisfied with the
      waiting time for telephone consultations (p<0.001) and more satisfied with
      waiting times for home visits than deputizing patients (p=0.020). Within the co
      operative, overall satisfaction, satisfaction with the doctor's manner and with
      the process of making contact was greater among those attending the primary care
      centre, and satisfaction with explanation and advice received greater than for
      patients receiving telephone consultations alone (p<0.01). Those receiving
      telephone advice reported increased information needs and help seeking during the
      following week (p< 0.05). CONCLUSIONS: Overall, patients were as satisfied with
      the co-operative as with practice-based or deputizing service arrangements,
      although many concerns were expressed about the quality of service provision.
      Differences in satisfaction were greater between forms of service delivery within
      the co-operative. Dissatisfaction with telephone consultations needs to be
      considered, together with issues relating to equity in access to out-of-hours'
      primary care centre consultations and the potential impact of NHS Direct.

PMID- 10912554
TI  - Inequalities in health: approaches by health authorities in an English health
      region.
AB  - BACKGROUND: In 1995 the Department of Health published Variations in health: what
      can the Department of Health do? This recommended that health authorities should
      have a comprehensive plan for identifying and tackling variations in health. We
      investigated how health authorities in the South and West Region were taking
      forward this work. METHODS: Semi-structured interviews and reviews of
      documentation were conducted in all health authorities in the South and West
      Region of England. RESULTS: All health authorities viewed tackling inequalities
      in health as important; however, explicit strategies did not exist and Health of
      the Nation targets were a vehicle for determining priorities of inequalities.
      Explicit corporate commitment was often weak. Analyses were being conducted to
      determine the magnitude of local health inequalities and to assist in designing
      appropriate interventions. The importance of alliance working was highlighted;
      much work was being done although success was variable. CONCLUSIONS: Efforts are
      being made throughout the South and West region to tackle inequalities in health.
      Although strategic vision at the corporate level was often lacking, there was
      evidence of commitment to taking the inequalities agenda forward within public
      health directorates. Strengthening of primary care and alliance working roles is
      essential. Recent national strategy documents, forthcoming legislation, and a
      review of health inequalities recognize the health effects of inequalities and
      require health authorities to collaborate with local partners to tackle these,
      and will offer opportunities to improve corporate commitment and alliance
      working. Uptake and success of these opportunities will have a major influence on
      progress in tackling health inequalities.

PMID- 10912553
TI  - Psychotropic medication use and risk of hormone-related cancers: the New York
      University Women's Health Study.
AB  - BACKGROUND: The use of psychotropic medications may increase the risk of hormone
      related cancers in females through increased gonadotropin secretion, but the data
      from epidemiologic studies are limited to evaluate the hypothesis. METHODS: The
      association between the use of psychotropic medications and cancer incidence was
      studied in a prospective cohort study that involves 15,270 women who participated
      in mammographic screening. The relative risks (RR) and 95 per cent confidence
      intervals (CIs) for cancer associated with the use of psychotropic medications
      were estimated by the Cox's proportional hazard model. RESULTS: During an average
      of 7.3 years of follow-up, 1,130 incident cases of cancer were identified,
      including 566 breast, 67 endometrial and 47 ovarian cancers. The use of any type
      of psychotropic medication at baseline was associated with increased risks of
      breast [relative risk (RR) = 1.39, 95 per cent CI 1.11-1.74], endometrial
      (RR=1.71; 95 per cent CI 0.93-3.14) and ovarian (RR= 1.48, 95 per cent CI 0.69
      3.16) cancers, whereas no increase in risk was observed for other cancers (RR =
      1.06). When the subjects were divided by menopausal status at baseline,
      premenopausal women tended to have higher risk of all hormone-related cancers (RR
      = 1.73, 95 per cent CI 1.27-2.35) than postmenopausal women (RR=1.23, 95 per cent
      CI 0.94-1.62). The magnitude of the RR associated with the use of these
      medications did not change by length of follow-up. Analysis by type of medication
      did not find that the association was limited to specific types. CONCLUSION: The
      observed association needs to be confirmed in further studies based on more
      detailed medication history.

PMID- 10912555
TI  - Comparison of the SF-36 health survey questionnaire with the Nottingham Health
      Profile in long-term survivors of a myocardial infarction.
AB  - BACKGROUND: Health-related quality of life, an important outcome measure in
      health interventions, can readily be assessed by questionnaire. Two widely
      evaluated examples are the Short Form 36 (SF-36) and Nottingham Health Profile
      (NHP) questionnaires, but as yet the discriminatory power of these tools has not
      been compared in a large population of patients with coronary heart disease.
      METHODS: All 4-year survivors of a myocardial infarction, identified from the
      Nottingham heart attack register, were sent the SF-36, NHP and additionally the
      Rose angina and dyspnoea questionnaires. Mean scores on the SF-36 and NHP were
      compared with age- and sex-adjusted norms in patients under and over 65 years.
      Sensitivity of the respective tools was assessed in distinguishing patients with
      differing degrees of cardiovascular symptomatology. RESULTS: In patients under 65
      years the SF-36 and NHP differed to the same extent from normative data--scores
      were lower in the comparable domains physical functioning/mobility, bodily
      pain/pain and energy/vitality, but not in mental health/emotional reaction
      scores. In social functioning/social isolation results were disparate--SF-36
      scores were lower and the NHP similar to normative data. In patients over 65
      years mean scores in all five domains were not significantly different from
      normative data for either tool. The SF-36 was more sensitive than the NHP at
      detecting the impact of breathlessness, particularly in patients with mild
      symptoms. Similarly, the SF-36, but not the NHP, could distinguish the effect of
      differing degrees of angina severity and frequency on social functioning.
      CONCLUSION: At least in myocardial infarction survivors, the SF-36 appears a more
      sensitive tool and may have benefits for assessing health-related quality of life
      in this patient group.

PMID- 10912556
TI  - Investigation of the association between excess winter mortality and socio
      economic deprivation.
AB  - BACKGROUND: Excess winter mortality is higher in England and Wales than in other
      European countries with similar or lower average winter temperatures. It might be
      expected that excess winter mortality would be higher in areas with greater socio
      economic deprivation, and if this were so preventive interventions could be
      directed at populations in these areas. The association between deprivation and
      excess winter mortality has not been adequately investigated in the past. The aim
      of this study was to look at the association between excess winter mortality and
      socio-economic deprivation, so that policy decisions to reduce this excess
      mortality could be appropriately directed. METHODS: Super Profile groups derived
      from the 1991 Census were used as a measure of socio-economic status. The age
      standardized excess winter death index (EWDI) was calculated for each Super
      Profile group, for the population of Bradford. The EWDI was also calculated for
      the manufacturing districts (Office for National Statistics area classification),
      a relatively deprived group, and compared with that for England and Wales.
      RESULTS: No significant trend was found in age-standardized excess winter
      mortality across the Super Profile groups. The manufacturing districts had a
      similar EWDI to the national value. CONCLUSION: Excess winter mortality is not
      associated with deprivation. Further research to identify the important
      aetiological factors and appropriate interventions to reduce excess winter
      mortality is needed.

PMID- 10912557
TI  - The new UK National Statistics Socio-Economic Classification (NS-SEC);
      investigating social class differences in self-reported health status.
AB  - BACKGROUND: The new UK National Statistics Socio-Economic Classification (NS-SEC)
      is theoretically based on differences in employment relations and conditions.
      Differences in employment relations could account for some of the often observed
      social class differences in health in the United Kingdom. This study investigates
      the associations of the NS-SEC with a well-validated health outcome measure--the
      Short Form health survey (SF-36). METHODS: Data from the Oxford Healthy
      Lifestyles Survey III (OHLS III, n = 6,454), a cross-sectional survey of adult
      men and women aged 18-64 randomly selected from the counties of Berkshire,
      Buckinghamshire, Northamptonshire and Oxfordshire, were analysed. The
      associations of the NS-SEC with the SF-36 physical and mental summary scores are
      investigated in a series of regression models controlling for age, lifestyle
      factors, housing and neighbourhood conditions. RESULTS: There are significant
      social class differences in the SF-36 physical and mental summary scores after
      controlling for age. When lifestyle, housing and neighbourhood conditions are
      controlled for, these differences reduce to non-significance. CONCLUSION: The NS
      SEC shows significant social class differences in health, further evidence for
      its construct validity. Social class differences in housing, neighbourhood and
      lifestyle factors appear to have a large role in understanding class differences
      in health. As it is grounded in theory, the NS-SEC is likely to prove a valuable
      tool for explanations of inequalities in health.

PMID- 10912558
TI  - Web page quality: can we measure it and what do we find? A report of exploratory
      findings.
AB  - BACKGROUND: The aim of this study was to report exploratory findings from an
      attempt to quantify the quality of a sample of World Wide Web (WWW) pages
      relating to MMR vaccine that a typical user might locate. METHOD: Forty pages
      obtained from a search of the WWW using two search engines and the search
      expression 'mmr vaccine' were analysed using a standard proforma. The proforma
      looked at the information the pages contained in terms of three categories:
      content, authorship and aesthetics. The information from each category was then
      quantified into a summary statistic, and receiver operating characteristic (ROC)
      curves were generated using a 'gold standard' of quality derived from the
      published literature. Optimal cut-off points for each of the three sections were
      calculated that best discriminated 'good' from 'bad' pages. Pages were also
      assessed as to whether they were pro- or anti-vaccination. RESULTS: For this
      sample, the combined contents and authorship score, with a cut-off of five, was a
      good discriminator, having 88 per cent sensitivity and 92 per cent specificity.
      Aesthetics was not a good discriminator. In the sample, 32.5 per cent of pages
      were pro-vaccination; 42.5 per cent were anti-vaccination and 25 per cent were
      neutral. The relative risk of being of poor quality if anti-vaccination was 3.3
      (95 per cent confidence interval 1.8, 6.1). CONCLUSION: The sample of Web pages
      did contain some quality information on MMR vaccine. It also contained a great
      deal of misleading, inaccurate data. The proforma, combined with a knowledge of
      the literature, may help to distinguish between the two.

PMID- 10912559
TI  - The accuracy of general practitioner records of smoking and alcohol use:
      comparison with patient questionnaires.
AB  - BACKGROUND: General practitioner (GP) records are increasingly being used as
      sources of information on potential confounders such as smoking use and alcohol
      intake in epidemiological studies. The aim of this study was to assess the
      accuracy of GP records on smoking use and alcohol intake compared with data from
      patient questionnaires. METHODS: Patients registered with 42 practices in
      Oxfordshire that agreed to take part in a post-marketing surveillance study of
      omeprazole were sent a postal questionnaire that included questions about alcohol
      and tobacco use. Two years later, data on these aspects of lifestyle were
      abstracted from the GP records. RESULTS: A total of 892 patients agreed to take
      part in the study; 804 (90 per cent) completed the postal questionnaire, and the
      records of 856 (96 per cent) were reviewed. Information on smoking and alcohol
      use was present in 74 per cent and 63 per cent of GP records, respectively.
      Agreement between the two data sources was moderate for both smoking (kappa =
      0.50) and alcohol use (kappa = 0.52). With regard to smoking, the main
      discrepancy between the two data sources was that 46 per cent (94/206) of
      patients who reported themselves as exsmokers were recorded as being never
      smokers in the GP record. With regard to alcohol, there were no systematic
      differences between the two data sources. CONCLUSION: Data from GP records on
      smoking status and alcohol use are incomplete and subject to some
      misclassification. This is a source of potential failed adjustment for
      confounding, which should be considered in epidemiological studies that make use
      of these records.

PMID- 10912561
TI  - Altogether now? Professional differences in the priorities of primary care
      groups.
AB  - BACKGROUND: Little is known about the similarities or differences with which
      Primary Care Group (PCG) Board members view the relative importance of the three
      functions with which they are charged, or how representative these views are of
      local primary care teams in general. This project explores the priorities of
      medical and nursing PCG Board members in relation to those of local General
      Practitioners (GPs) and practice nurses they represent. METHODS: Postal
      questionnaires were sent to GPs (n=236) and practice nurses (n= 137); structured
      telephone interviews were carried out with PCG Board members (n=61) in East
      Sussex, Brighton and Hove. RESULTS: There are large differences between the views
      of GPs and those of their nursing colleagues on how PCG Board members should
      determine priorities in their work. There are also marked differences in the
      priorities of PCG Boards (of whom the majority are GPs) and non-Board member GPs.
      Whereas around two-thirds of PCG Board members believe that improving health
      generally and reducing inequalities in particular are the most important tasks
      before them, this view is not shared by most GPs in the same localities, who are
      generally more concerned about commissioning services. There is some doubt among
      GPs generally about the suitability of PCG Board members as a vehicle for the
      tasks they have been set, and this doubt is also found among PCG Board members
      themselves. CONCLUSIONS: The priorities of PCG Board members of different
      disciplines need to be aligned in order that they have a clear focus on the tasks
      before them. PCG Boards must also have priorities that are consistent with the
      local practitioners who elected them. Effective systems of communication will
      need to be developed between PCG Board members, Health Authorities and individual
      Primary Care Groups. Local flexibility is essential to the success of Primary
      Care Groups, but tackling inequalities in health must always be at the forefront
      of their role.

PMID- 10912562
TI  - Cancer registries--future development and uses in Britain.
AB  - Cancer registries are a vital source of information on cancer epidemiology and
      cancer services. Their role has changed dramatically over the past 15 years. A
      number of factors will affect their future role, including health service
      changes, information technology, development of clinical datasets and greater
      demand for both health service and public information. The potential of cancer
      registration needs to be realized by clinicians and health authorities: how they
      can use the data, its limitations, and how they can support and influence it
      through this period of change. A strategic direction is needed so that cancer
      registries develop into a dynamic, interactive source of knowledge for the twenty
      first century.

PMID- 10912560
TI  - Trade-offs between location and waiting times in the provision of health care:
      the case of elective surgery on the Isle of Wight.
AB  - BACKGROUND: Recent UK government documents have stated that, within the National
      Health Service, consumers should be more involved in decision-making. This study
      considered the technique of discrete choice conjoint analysis (DCCA) for
      eliciting community views regarding the importance of reducing waiting times.
      More specifically, the study aimed to establish whether residents living on the
      Isle of Wight are prepared to travel to the mainland for elective surgery where
      waiting times are shorter but travel costs may be greater, and, further, if
      residents are willing to travel, what reduction in waiting time and increase in
      travel costs would be acceptable. METHODS: A DCCA questionnaire was sent to a
      random sample of 1,000 individuals living on the Isle of Wight. RESULTS: Seventy
      eight per cent of respondents were willing to travel to the mainland for elective
      surgery. Of these, 48 per cent always chose the mainland and 30 per cent traded
      between island and mainland, depending on the levels of waiting time and travel
      costs. Whereas 'traders' preferred the Isle of Wight, they would forgo their
      preferred location if waiting times were reduced by at least 3.9 months, and they
      were willing to pay over 12 for a 1 month reduction in waiting time. Different
      combinations of waiting time reductions and travel cost increases that were
      acceptable to traders were estimated. CONCLUSIONS: Carrying out elective surgery
      on the mainland offers the potential to reduce waiting lists for island
      residents. The majority of respondents would be willing to travel to the
      mainland. However, one-fifth of respondents were not willing to travel to the
      mainland for elective surgery. The preferences of this group are important in
      policy decisions. More generally, the paper demonstrates the potential
      application of DCCA to public health issues.

PMID- 10912563
TI  - Tuberculosis screening of new entrants; how can it be made more effective?
AB  - BACKGROUND: The importance of extending TB screening to all new entrants has been
      shown by the occurrence of cases of active TB and high rates of those needing
      prophylaxis or BCG protection. TB is particularly likely to be prevalent in
      populations with large numbers of refugees, but high rates in immigrants have
      been reported consistently both in this country and elsewhere in Europe. METHOD:
      This paper examines possible reasons for a low uptake of screening by immigrants
      in the United Kingdom and describes initiatives, some of which have already been
      launched in East London, by which access to screening could be increased.
      RESULTS: Screening at the new patient check-up by general practitioners has been
      shown to be practicable and effective in an East London pilot. This screening
      method could be expanded throughout East London and is applicable to other areas.
      Other ways of improving access to screening through other agencies have also been
      found to be acceptable. CONCLUSION: No one screening system is likely to be
      effective and pilots of methods of extending the access to new entrants need to
      be carried out and evaluated urgently.

PMID- 10912564
TI  - Development of the Paediatric Appropriateness Evaluation Protocol for use in the
      United Kingdom.
AB  - BACKGROUND: This paper describes a study to develop and test an instrument to
      measure the level of appropriate admissions and days of care in the paediatric
      hospital population. METHODS: The American version of the Paediatric
      Appropriateness Evaluation Protocol (PAEP) was modified by the consensus views of
      a panel of paediatricians and general practitioners. Reliability was tested in a
      pilot study in a random sample of 47 admissions from two district general
      hospitals. RESULTS: The agreement beyond chance for the raters using the PAEP for
      admission criteria was excellent (kappa = 0.848). It was poor (kappa = 0.345) for
      clinicians using subjective judgement. The agreement beyond chance for the day of
      care criteria was good (kappa =0.54). Trained reviewers achieved much higher
      reliability using the PAEP. CONCLUSION: The modified PAEP achieved high
      reliability and was judged acceptable by clinicians to retrospectively assess the
      appropriateness of admissions in the UK setting.

PMID- 10912565
TI  - Assessing the appropriateness of paediatric hospital admissions in the United
      Kingdom.
AB  - BACKGROUND: In order to assess whether the documented rise in paediatric
      admissions was due to inappropriate admissions, an objective measure of the
      appropriateness of paediatric admissions, modified for use in the United Kingdom,
      was used to measure the level of inappropriate admissions. The relationship of
      appropriateness of admissions to age, gender, time of admission and source of
      referral was investigated. METHODS: A retrospective review was carried out of a
      sample of paediatric records in 13 NHS district general hospitals in South
      Eastern England between April 1990 and March 1991 using the Paediatric
      Appropriateness Evaluation Protocol (PAEP) modified for use in the United
      Kingdom. RESULTS: A total of 3,324 paediatric admissions in 13 hospitals were
      assessed. Eight per cent of the sampled admissions were inappropriate. Age [odds
      ratio (OR)=0.87], gender (OR = 1.39) and weekend admissions (OR = 1.42) were
      associated with inappropriate admissions. After controlling for these factors,
      there was no significant variation between hospitals. CONCLUSION: The low level
      of inappropriate admissions may be a reflection of well-developed primary care
      services in the United Kingdom. Alternatives to hospital admission for the
      assessment of minor self-limiting illness in young children may have a role in
      reducing inappropriate admissions.

PMID- 10912566
TI  - Quarterly Communicable Disease Review October to December 1999--From the PHLS
      Communicable Disease Surveillance Centre.

PMID- 10912567
TI  - Minority ethnic groups and our healthier nation.

PMID- 10912568
TI  - Military health care.

PMID- 10912569
TI  - What should a health authority do to assess health needs associated with stroke?

PMID- 10912570
TI  - How does the prevalence of specific morbidites compare with measures of socio
      economic status at small area level?

PMID- 10912571
TI  - A novel synthetic DNA minor groove binder, MS-247: antitumor activity and
      cytotoxic mechanism.
AB  - PURPOSE: MS-247 is a novel synthetic compound possessing a DNA-binding moiety and
      a DNA-alkylating residue, chlorambucil. In this study, we evaluated the antitumor
      activity of MS-247 against murine tumor cell lines and its effects on DNA
      molecules in both cell-free and cellular systems. METHODS: The in vitro cytotoxic
      activity of MS-247 was evaluated against four murine tumor cell lines, P388,
      L1210, Colon26 and B16, and its in vivo antitumor activity was also tested in
      comparison with Adriamycin (ADM), cisplatin (CDDP) and paclitaxel. The ability of
      MS-247 to associate with the DNA minor groove was assessed by measuring quenching
      of Hoechst 33342 fluorescence. DNA-DNA interstrand crosslinks (ICL) were detected
      by an alkaline elution assay for cellular DNA and a band-shift assay using the
      plasmid pBR322. The effects of MS-247 on macromolecule synthesis (DNA, RNA and
      proteins) were examined by measuring incorporation of the radiolabeled
      precursors. RESULTS: MS-247 exhibited in vitro cytotoxicity with IC(50) values
      ranging 11 to 500 nM, and MS-247 given i.v. showed strong in vivo antitumor
      activity against i.p.-implanted L1210 leukemia cells and s.c.-implanted Colon26
      carcinoma cells, and moderate activity against i.p.-implanted P388 leukemia cells
      but no apparent activity against s.c.-implanted B16 melanoma cells. MS-247
      reversibly displaced Hoechst 33342 bound to DNA within a few minutes, and
      irreversibly formed ICL within 1-6 h in both the cell-free system and the
      cellular system. These results suggest that an association of MS-247 with the DNA
      minor groove occurred more quickly than ICL formation. The inhibition of DNA
      synthesis was more prominent than the inhibition of RNA and protein synthesis in
      L1210 cells exposed to MS-247, and a 6-h incubation with MS-247, which formed
      apparent ICL in the cellular system, strongly inhibited DNA synthesis. This
      result suggests that impairment of DNA replication preceded the inhibition of RNA
      and protein synthesis and that ICL formation greatly contributed to the
      inhibition of macromolecule synthesis. CONCLUSION: The results of this study
      suggest that MS-247 exerts its cytotoxic effect through impairment of DNA
      function by getting into the minor groove of DNA and subsequently forming ICL. MS
      247 has potent antitumor activity with a different spectrum from the activity of
      clinically proven antitumor agents such as paclitaxel, ADM and CDDP against
      several murine tumor cell lines. This result suggests that MS-247 may be useful
      for the treatment of human cancers.

PMID- 10912572
TI  - Pegylated liposome-encapsulated doxorubicin and cisplatin in the treatment of
      head and neck xenograft tumours.
AB  - PURPOSE: To evaluate the in vitro and in vivo activity of unencapsulated
      doxorubicin (DOX) and cisplatin (CDDP) and their pegylated liposome encapsulated
      counterparts (PLED and PLEC) in a subcutaneous model of human squamous cell
      cancer of the head and neck. METHODS: In vitro cytotoxicity was determined by
      means of the sulphorhodamine B assay and in vivo activity was assessed in terms
      of tumour growth delay following single intravenous doses of the various agents.
      Treatment-related toxicity was evaluated by means of serial weight measurement.
      RESULTS: The IC(50) values for DOX (12.1-fold) and CDDP (21.5-fold) were lower
      than for their liposome-encapsulated counterparts. When the two unencapsulated
      agents were compared, the IC(50) value for DOX was 16-fold lower than that for
      CDDP. In the in vivo studies, liposomes containing DTPA (PLEDTPA) exerted no
      effect on KB xenograft tumours when compared to untreated controls (P > 0.1).
      PLED was significantly more effective than DOX at doses of 2 mg/kg, 4 mg/kg and 8
      mg/kg (P < 0.001 for all comparisons). At the 8 mg/kg dose, 7/13 animals treated
      with PLED were free of disease at 60 days, compared to 0/12 treated with DOX.
      PLEC displayed superior activity in comparison to CDDP at the 4 mg/kg dose level
      (P < 0.001), although at doses of 2 mg/kg and 10 mg/kg this comparison only
      reached borderline statistical significance (0.1 > P > 0.05). The highest dose
      level of 20 mg/kg was fatal to all animals in the CDDP group but well-tolerated
      by the animals in the PLEC group. On the basis of serial weight measurements,
      both PLED and PLEC were shown to be tolerated better than DOX and CDDP.
      CONCLUSION: Both PLED and PLEC were shown to exert significant activity against
      head and neck xenograft tumours, with PLED showing particular efficacy.

PMID- 10912573
TI  - Pharmacokinetics and toxicity of high-dose intravenous methotrexate in the
      treatment of leptomeningeal carcinomatosis.
AB  - PURPOSE: To evaluate the pharmacokinetics and toxicity of high-dose intravenous
      (i.v.) methotrexate (MTX) with leucovorin in patients with meningeal
      carcinomatosis. METHODS: Of 16 eligible patients entered on this study, 13 with
      meningeal carcinomatosis from breast cancer, lung cancer, or osteosarcoma were
      treated with MTX at loading doses of 200-1500 mg/m2, followed by a 23-h infusion
      of 800-6000 mg/m2. Three patients without meningeal disease were also treated and
      the cerebrospinal fluid (CSF) MTX concentrations were compared in patients with
      and without central nervous system (CNS) disease. RESULTS: Patients without CNS
      disease had lower CSF MTX concentrations relative to the plasma MTX levels than
      those with CNS disease, who all had CSF MTX concentrations above the target
      cytotoxic concentration (1 microM). The CSF MTX concentrations correlated better
      with the free and the total plasma MTX concentrations than with the doses. The
      mean half-life of CSF MTX was 8.7 +/- 3.4 h. The mean plasma clearance of MTX was
      not significantly different in patients with CNS disease (84 +/- 41 ml/min per
      m2) versus without CNS disease (59 +/- 38 ml/min per m2). All toxicities were
      grade 2 or less except grade 3 hematologic toxicity. No patient had an objective
      response in the CSF. CONCLUSION: This trial demonstrates that potentially
      cytotoxic CSF MTX concentrations (> 1 microM) are delivered safely by i.v.
      infusion, a less invasive and better distributed CSF therapy compared with
      intrathecal MTX. Because of the excellent pharmacokinetics and toxicity, high
      dose i.v. MTX should be evaluated at a loading dose of 700 mg/m2 and a 23-h
      infusion of 2800 mg/m2 with leucovorin in less heavily pretreated patients with
      carcinomatous meningitis.

PMID- 10912574
TI  - Evaluation of toremifene for reversal of multidrug resistance in renal cell
      cancer patients treated with vinblastine.
AB  - PURPOSE: Expression of P-glycoprotein (Pgp), which confers the multidrug
      resistance (MDR) phenotype, is thought to contribute to the insensitivity of
      renal cell cancer (RCC) to chemotherapy. The development of Pgp inhibitors for
      clinical application has been hampered by unacceptable toxicity at doses required
      to achieve adequate cellular concentration. Toremifene is able to reverse MDR and
      sensitise RCC to vinblastine in vitro. However, in vivo toremifene is tightly
      bound to serum proteins, in particular the acute phase protein alpha1-acid
      glycoprotein (AAG), which may limit tissue availability. In this phase I-II study
      we assessed the tolerability of short courses of high dose toremifene in
      combination with vinblastine and evaluated the key determinants of MDR reversal
      in vivo. METHODS: Twenty-seven patients with metastatic RCC received escalating
      doses of oral toremifene for 3 days every 2 weeks in combination with vinblastine
      6 mg/m2 i.v. on day 3 of each cycle. The serum concentration of toremifene, its
      metabolites and AAG were measured and the effect of patients' serum on inhibition
      of Pgp in vitro was determined. RESULTS: Twenty-six patients were evaluable for
      response. Eight patients (31%) had stable disease and 18 patients (69%)
      progressive disease. The mean serum concentration of toremifene at 780 mg daily
      for 3 days was 7.82 microM [standard deviation (SD) 2.48, range 2.50 to 14.70],
      which exceeds that known to reverse MDR in vitro. The serum concentration of the
      major metabolite of toremifene, N-demethyltoremifene, which also reverses MDR,
      was 5.13 microM (SD 1.78, range 1.80 to 9.00). In 60% of patients the pre
      treatment AAG concentration was above that known to block the effects of
      toremifene in vitro. However, addition of serum from patients on toremifene to
      MCF-7 adr cells in vitro inhibited Pgp-mediated efflux of rhodamine 123.
      CONCLUSIONS: We have shown that short course, high-dose toremifene in combination
      with vinblastine is generally well tolerated and that the concentration of
      toremifene required to reverse MDR in vitro is achievable in vivo.

PMID- 10912576
TI  - Pharmacokinetics of 2-chloro-2'-deoxyadenosine administered subcutaneously or by
      continuous intravenous infusion.
AB  - PURPOSE: Cladribine (2-chlorodeoxyadenosine, 2-CDA) is effective in the treatment
      of various lymphoproliferative disorders. In the standard protocol the compound
      is administered by continuous intravenous (i.v.) infusion. In order to allow
      outpatient therapy alternative modes of administration such as subcutaneous
      (s.c.) injection would be desirable. The aim of the present study was to compare
      the pharmacokinetics of 2-CDA after i.v. and s.c. administration. PATIENTS AND
      METHODS: Nine patients received 0.1 mg/kg 2-CDA per 24 h on one occasion by
      continuous i.v. infusion and on another occasion as a bolus subcutaneously. The
      concentrations of 2-CDA in the plasma and urine were determined by HPLC. RESULTS:
      During i.v. infusion the concentration of 2-CDA in the plasma reached a plateau
      after 4-8 h, whereas with s.c. administration almost ten times higher peak
      concentrations were reached within 20 to 60 min. A two-compartment model was
      fitted to the data points whereby the goodness-of-fit statistics showed R2 values
      of > 0.98. The calculated rate of elimination, k(elim), averaged 0.336 h(-1) with
      s.c. and 0.397 h(-1) with i.v. administration. The estimated volumes of
      distribution were 1.67 and 1.58 l/kg. The areas under the concentration time
      curves (608 +/- 65 pmol x h/ml after s.c. administration vs 571 +/- 50 pmol x
      h/ml during i.v. infusion) and the urinary excretion of 2-CDA in 24 h (4.75 +/-
      0.95 vs 3.55 +/- 0.53 micromol/24 h) were similar in both groups, indicating
      identical bioavailability. CONCLUSIONS: Although the pharmacokinetic profile of 2
      CDA administered s.c. differs substantially from the profile of a continuous i.v.
      infusion the areas under the plasma concentration time curves, the urinary
      excretion of unchanged drug and the estimated pharmacokinetic variables were
      similar with both modes of administration, indicating that the different time
      courses of the plasma concentration did not influence the fraction metabolized or
      eliminated.

PMID- 10912575
TI  - Effects of the aromatase inhibitor anastrozole on serum oestrogens in Japanese
      and Caucasian women.
AB  - PURPOSE: Substantial differences in plasma oestrogen disposition have been
      reported between Japanese and Caucasian women, but there are currently few data
      available on the relative endocrinological effects of aromatase inhibitors in
      these two groups. Hence, the effects of the nonsteroidal aromatase inhibitor
      anastrozole on serum oestrogen concentrations were compared in 24 healthy
      postmenopausal Japanese women and 24 healthy postmenopausal Caucasian women.
      METHODS: Anastrozole, 1 mg/day, was given once daily for 16 days. Serum
      oestradiol and oestrone sulphate levels were measured on three consecutive days
      beginning 2 days before the first dose, and on a further three consecutive days
      beginning on the penultimate day of dosing. Trough concentrations of anastrozole
      (measured 24 h after dosing) were also determined during the same periods.
      RESULTS: There were no substantial differences in plasma oestrogen concentrations
      between the Japanese and Caucasian women at baseline. On average, anastrozole
      suppressed serum oestradiol and oestrone sulphate levels by approximately 87% and
      93%, respectively, for both Japanese and Caucasian women, and minimum plasma
      anastrozole concentrations at steady-state (anastrozole C(min)) were also similar
      in both groups. Statistical analysis of serum oestradiol and serum oestrone
      sulphate levels, and plasma anastrozole C(min) showed that there were no
      statistically significant differences between the Japanese and Caucasian women.
      CONCLUSION: Neither the pharmacodynamic effects of anastrozole on serum
      oestrogens nor the pharmacokinetics of anastrozole differ between postmenopausal
      Japanese and Caucasian women. Hence, these findings suggest that the therapeutic
      benefits of anastrozole in Caucasians will be predictive of the drug's effect in
      Japanese women and support the use of anastrozole in postmenopausal Japanese
      women with breast cancer.

PMID- 10912577
TI  - Dose escalation and pharmacokinetic study of irinotecan in combination with
      paclitaxel in patients with advanced cancer.
AB  - PURPOSE: Based on preclinical data demonstrating synergy between camptothecin
      analogues and taxanes, we determined the maximum tolerated dose (MTD) of
      irinotecan that could be given in combination with a fixed dose of paclitaxel of
      75 mg/m2, when both drugs were delivered on a weekly schedule. The
      pharmacokinetics of this combination were explored to determine whether the
      sequence of administration affected the elimination of irinotecan. METHODS: For
      the first cycle patients with advanced cancer were treated with irinotecan given
      as a 90-min infusion followed immediately by paclitaxel given at a dose of 75
      mg/m2 over 1 h. The sequence of drug administration was reversed in subsequent
      cycles for most patients. Chemotherapy was given weekly for 4 weeks, followed by
      a 2-week rest. In selected patients, plasma concentrations of irinotecan were
      determined by high-performance liquid chromatography during the first 24 h of
      cycle 1 and after the first dose of cycle 2 to determine whether the order of
      drug administration affected the elimination of irinotecan, or the toxicologic
      effects of the chemotherapy. RESULTS: A total of 53 cycles were delivered to 21
      patients. Reversible neutropenia was dose-limiting. Suppression of the other
      blood cell elements was modest. There was one partial response in a man with a
      previously treated cholangiocarcinoma that lasted 26 weeks. Prolonged
      stabilization of disease (6 months or more) was observed in five of the patients
      (24%). At the recommended dose of irinotecan (50 mg/m2), transfusions of red
      cells and platelets were not required. The sequence of drug administration
      produced no significant differences in the pharmacokinetic parameters of
      irinotecan or SN-38, which were similar to the values reported when irinotecan is
      administered alone. The most prominent nonhematologic toxicities were mild
      diarrhea and fatigue. CONCLUSIONS: The recommended dose of irinotecan on this
      schedule is 50 mg/m2. The sequence of drug administration affects neither the
      elimination of irinotecan nor the chemotherapy-related toxicity. This combination
      is well tolerated and causes minimal clinical side effects.

PMID- 10912579
TI  - Feasibility and pharmacokinetics of intraperitoneal suramin in advanced
      malignancy.
AB  - PURPOSE: Bioactive lipids have been causally linked to intraabdominal
      malignancies such as ovarian cancer. In advanced tumors confined to the
      peritoneal cavity. inhibition of lipid growth factors present in ascites might
      induce tumor remissions. The systemic toxicity of the growth factor inhibitor
      suramin has so far hampered its use in standard oncologic practice, but this
      could be alleviated by intraperitoneal administration. In this study the
      feasibility, toxicity and pharmacokinetics of intraperitoneal suramin
      administration are described. METHODS: Patients with histologically verified
      cancer confined to the abdominal cavity, for which no effective therapy was
      available, were treated with intraperitoneal suramin through a Tenckhoff
      catheter. Patients with ascites were treated with low-volume continuous i.p.
      infusions of 500 mg/24 h, and patients without ascites were treated with
      intermittent large-volume i.p. infusions of 1000 mg three times a week. Regular
      pharmacokinetic sampling of plasma and ascites fluid was carried out. Patients
      were treated for 6 weeks or until development of progressive disease or until
      plasma suramin levels exceeded 250 mg/l. RESULTS: Nine patients were treated in
      ten periods, three with intermittent i.p. suramin, and seven with continuous i.p.
      suramin, for a median of 28.5 days (16-42 days), with a median suramin dose of 12
      g (range 9 21 g ). Treatment was discontinued because of high systemic suramin
      levels in three patients (all in the intermittent schedule), progressive disease
      (five patients) or completion of planned treatment (one patient). Toxicity was
      mild, without any of the systemic side effects commonly associated with suramin.
      Intraperitoneal suramin levels were consistently higher than plasma levels in all
      patients, but this effect was most marked in the continuous infusion schedule.
      CONCLUSIONS: Intraperitoneal suramin infusion in patients with advanced
      peritoneal cancers is feasible and well-tolerated. Continuous low volume i.p.
      infusion in patients with ascites confers the largest pharmacokinetic advantage.

PMID- 10912578
TI  - Reduction of 5-fluorouracil (5-FU) gastrointestinal (GI) toxicity resulting from
      the protection of thymidylate synthase (TS) in GI tissue by repeated simultaneous
      administration of potassium oxonate (Oxo) in rats.
AB  - PURPOSE: An important cytotoxic effect of 5-fluorouracil (5-FU) is the
      inactivation of thymidylate synthase (TS) (EC 2.1.1.45) activity by the formation
      of a ternary complex consisting of covalently bound 5-fluorodeoxyuridine 5'
      monophosphate (FdUMP), TS and 5,10-methylenetetrahydrofolate (CH2FH4). The
      gastrointestinal (GI) toxicity of 5-FU is also caused by its phosphorylation in
      the GI tract. Potassium oxonate (O(XO)) competitively inhibits pyrimidine
      phosphoribosyltransferase (EC 2.4.2.10), which converts 5-FU to 5-fluorouridine
      5'-monophosphate (FUMP) in vitro. In this study the benefits of combining Oxo and
      tegafur (FT), which is a masked compound of 5-FU, in reducing the GI toxicity of
      5-FU and in protecting the activity of TS in the normal GI tissues were
      evaluated. METHODS: We administered orally a preparation of 1 M FT and 0.4 M 5
      chloro-2,4-dihydroxypyridine (CDHP) with or without 1 M O(XO) (called S-1 and FT
      + CDHP, respectively) or vehicle only (control) to rats for ten consecutive days
      and compared the toxicity, the histopathological findings and the free TS
      activity in the GI tissues of the treated rats. RESULTS: During the experimental
      periods, the signs of toxicity, such as a decrease in body weight, diarrhea and
      death, were only observed in the rats treated with FT + CDHP. The
      histopathological findings in the ileum and colon samples from rats treated
      consecutively with S-1 on day 1, day 4, day 7 and day 10 were less frequent and
      more mild than in the samples from rats treated with FT + CDHP. Furthermore, the
      free TS activities in the ileum samples of rats given S-1 and FT + CDHP were
      significantly decreased compared with the activity in samples from the control
      rats throughout the experimental periods. The free TS activities in GI tissues of
      rats treated with S-1 were higher than the TS activities in tissues from rats
      treated with FT + CDHP daily from day 4 to day 10, although activities in S-1
      treated rat were decreased to almost same low levels as in FT + CDHP-treated rats
      on day 1. CONCLUSIONS: Our results suggest that repeated simultaneous
      administration of Oxo and FT can effectively protect the activity of TS by
      decreasing FdUMP via FUMP from 5-FU in GI tissue, and may lead to a reduction in
      GI toxicity.

PMID- 10912580
TI  - Primary treatment of low-grade non-Hodgkin's lymphoma using an all oral
      anthracycline-containing regimen, chlorambucil, idarubicin, dexamethasone (CID)-
      a phase II study.
AB  - PURPOSE: The majority of patients with low-grade non-Hodgkin's lymphoma (LGNHL)
      are in the older age groups and are thus less able to tolerate aggressive
      treatment. Chlorambucil, alone and in combination, has been widely accepted as
      the initial treatment of choice for many years. The availability of an
      anthracycline which could be given orally in combination with chlorambucil and
      steroid led us to investigate the efficacy and toxicity of this novel regimen.
      METHODS: Patients (age less than 70 years) with a histologically confirmed
      diagnosis of LGNHL (Kiel classification) were eligible for the study if they had
      no previous chemotherapy. Treatment consisted of chlorambucil 20 mg/ m2 daily for
      3 days given on each day in three divided doses, idarubicin 10 mg/m2 for 3 days
      before breakfast, and dexamethasone 4 mg twice daily for 5 days. All drugs were
      given orally. Treatment was repeated every 21 days for a maximum of six courses.
      The regimen was assessed for toxicity and response. RESULTS: A total of 72
      patients were registered, and 64 were eligible (median age 52 years). Toxicity
      was assessed for all cycles given (347). The predominant toxicity was
      haematological, but in only one course did grade 4 neutropenia (less than 0.5 x
      10(9)) occur. Alopecia was not a problem. Full doses of the treatment were
      administered to 40% of the patients, with no delays or dose reductions. The
      overall response rate was 83%. Six patients had static disease and two progressed
      on treatment. Lactate dehydrogenase (LDH) was found to be a good predictor of
      response to treatment. Of 12 patients documented to have raised LDH, 5 failed to
      respond to treatment, compared to 1 of 32 patients who had a normal LDH (chi2
      10.65, P < 0.002). With a minimum follow-up of 4 years for all patients actuarial
      5-year event-free survival was 22% and overall survival was 65%. However, in
      patients with best and intermediate risk LGNHL (by the SNLG Prognostic Index for
      Low Grade Disease) overall survival are 88% and 64%, respectively. CONCLUSIONS:
      This novel regimen was effective and well tolerated.

PMID- 10912581
TI  - Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of
      acute toxicity in rats.
AB  - PURPOSE: After more than 50 years of methotrexate (MTX) treatment of acute
      lymphoblastic leukaemia (ALL), it is currently believed that as long as dose
      escalations are followed by adequate leucovorin rescue guided by monitoring MTX
      serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD
      MTX) can be tolerated without life-threatening toxicity. However, our recent
      experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate
      that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1
      mM, which is below the levels routinely found in patients on HD-MTX, demonstrate
      intolerable toxicity and some animals die within 8 h. Electron microscopy
      indicates that endothelial cell and platelet functions are perturbed. Since
      animal data are lacking, and interspecies differences not known, we wanted to
      investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of
      short-term effects. The maximum tolerated dose was chosen instead of LD(50) for
      reasons of animal welfare. METHODS: We infused MTX and 7-OH-MTX into
      anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were
      given as a bolus plus continuous infusion. The dose-finding ranges were 1.8 11.3
      g/kg MTX and 0.1-1.2 g/kg 7-OH-MTX. RESULTS: The maximum tolerated dose was
      between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum
      concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period
      were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or
      7-OH-MTX doses and concentrations died after sudden reductions in heart rate and
      blood pressure. CONCLUSIONS: We demonstrated a lower maximum tolerated dose of 7
      OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the
      therapeutic range after HD-MTX. If the rat/human interspecies differences are not
      large, our data may indicate that HD-MTX regimens should not be further dose
      intensified, due not so much to the effects of MTX as to those of 7-OH-MTX.

PMID- 10912582
TI  - Selenium compounds prevent the induction of drug resistance by cisplatin in human
      ovarian tumor xenografts in vivo.
AB  - PURPOSE: The development of drug resistance is a major cause for the failure of
      chemotherapy, particularly in ovarian cancer. Most previous research has focused
      on approaches to reverse drug resistance once it has arisen, that is, on the use
      of agents which can make drug-resistant tumors more sensitive to chemotherapy. We
      have suggested the feasibility of an alternative approach: the use of specific
      agents to prevent the development of resistance. METHODS: We designed an in vivo
      system to assay for the ability of compounds to prevent the induction of
      resistance by cisplatin. In this system, mice bearing tumors (which originated
      from A2780 human ovarian tumor cells) were treated with a low dose (2.6 mg/kg) of
      cisplatin and the tumors rapidly developed resistance to subsequent cisplatin
      treatment. Cell lines initiated from these tumors retained the resistant
      phenotype even after several months in culture. RESULTS: When either selenite or
      selenomethionine were administered (i.p., 1.5 mg/kg) close to the time of the
      initial cisplatin treatment, the induction of resistance was prevented. Similar
      treatments with sulfite or methionine had no effect on the induction of
      resistance by cisplatin. Studies in cells from treated tumors have indicated that
      the selenium compounds may prevent the induction of resistance by preventing a
      cisplatin-induced increase in glutathione level. CONCLUSIONS: Selenium compounds
      specifically prevent the induction by cisplatin of drug resistance in human
      ovarian tumors in vivo.

PMID- 10912583
TI  - A peptidomimetic inhibitor of ras functionality markedly suppresses growth of
      human prostate tumor xenografts in mice. Prospects for long-term clinical
      utility.
AB  - PURPOSE: These studies sought to evaluate the antitumor properties of an
      inhibitor of ras functionality, L-744,832, which acts at the level of its
      associated protein farnesyltransferase. METHODS: Studies were carried out to
      measure the effects of L-744,832 alone and in combination with paclitaxel (PTXL)
      against TSU-PR1, DU-145 and PC-3 human prostate tumors xenografted to NCR-nul
      (AT) mice. Tumor-bearing mice were treated on a schedule of daily for 5 days x2
      or 3 with the MTD of L-744,832 and every 3-4 days x4 with the MTD of PTXL
      starting 3-5 days after tumor implantation. Tumor volume in millimeters (4/3pir3)
      was measured 3 5 days after cessation of treatment and the increase in tumor
      volume in treated and control groups compared. Statistical analysis was carried
      out by the Chi-squared test. RESULTS: L-744,832 at its MTD markedly inhibited the
      growth of all three tumors (TIC for increase in tumor mass varied from 11% to 15%
      and inhibition of growth had a rapid onset (within 1-2 days) and was independent
      of ras gene status. Estimated tumor doubling times were 8-12-fold greater in
      treated animals than in control animals. Treatment with L-744,832 for as long as
      3 weeks had no untoward effects on the mice as determined by gross examination or
      necropsy. Administration of L-744,832 with this same dose and schedule
      potentiated the growth-inhibitory effect of PTXL at its MTD and induced some
      regression of TSU-PR1 with no obvious deleterious effects on the mice.
      CONCLUSIONS: L-744,832 could be safely administered over a protracted period of
      time to mice at doses which were markedly inhibitory to the growth of three human
      prostate tumor xenografts and in combination with PTXL was also well tolerated
      and brought about some regression of the TSU-PR1 tumor. Overall, these results
      suggest that L-744,832 could be clinically useful for long-term treatment of
      early-stage prostate cancer in patients and as an adjunct to cytotoxic therapy
      for late stages of this disease.

PMID- 10912584
TI  - Phenylsilsesquioxane fluid: developmental toxicity studies in rats and rabbits
      following oral administration.
AB  - Phenylsilsesquioxane fluid (PSF) is used widely in the personal care industry and
      is a common component of skin and oral care products. The potential developmental
      toxicity of PSF was evaluated in rats and rabbits. Groups of 25 sperm-positive
      Sprague-Dawley rats (Taconic Farms) and 15 sperm-positive New Zealand White
      rabbits (HRP) were administered dose levels of 50, 500, or 1000 mg/kg PSF in corn
      oil. Vehicle control groups of equal size were administered corn oil alone. Rats
      were dosed daily (5 ml/kg) on gestation d 6-15 and sacrificed on gestation d 20,
      while rabbits were dosed daily (1.5 ml/kg) on gestation d 6-18 and sacrificed on
      gestation d 29. The fetuses were removed by cesarean section and examined for
      gross external, visceral, cephalic, and skeletal anomalies. No treatment-related
      clinical signs of toxicity were observed. No marked effects upon maternal food
      consumption, body weight, body weight gain, or uterus or liver weight were
      detected. Fetal viability and body weight, as well as developmental endpoints,
      were unaffected by treatment. Accordingly, exposure of pregnant rats or rabbits
      to 50, 500, or 1000 mg/kg of PSF during the period of major organogenesis did not
      result in any biologically significant adverse or teratogenic effects in the dams
      or fetuses.

PMID- 10912585
TI  - Derivation of shellfish harvest reopening criteria following the New Carissa oil
      spill in Coos Bay, Oregon.
AB  - Oil spills in Alaska, California, Maine, and other states have raised concerns
      regarding potential contamination of fish and shellfish, and have led to
      temporary closures of seafood harvests while health risks are assessed. Lacking
      standardized protocols, these assessments are generally ad hoc, site-specific
      efforts, with significant differences in risk evaluation criteria. This article
      describes the response of a state health agency to shellfish contamination
      following an oil spill on the Oregon coast, and discusses some of the factors
      that can complicate the evaluation of potential health risks from consumption of
      oil-contaminated shellfish. On 4 February 1999, the Japanese-owned cargo ship M/V
      New Carissa, carrying an estimated 400,000 gallons of light diesel and heavy fuel
      oil, ran aground 2 miles north of Coos Bay, Oregon. Damage to the ship's hull
      from the grounding and pounding surf caused the release of an estimated 25,000 to
      70,000 gallons of oil. Concern for potential contamination of local recreational
      shellfish and commercial oyster beds prompted the Oregon Department of
      Agriculture (ODA) to close shellfish harvesting in Coos and Douglas counties. ODA
      requested assistance from the Oregon Health Division in the derivation of risk
      based criteria for reopening the shellfish harvest. Criteria were developed for
      the primary contaminants of concern, polycyclic aromatic hydrocarbons (PAHs)
      expressed as total benzo[a]-pyrene (BaP) equivalents. "Safe" (<10 microg/kg) and
      "unsafe" (>45 microg/kg) BaP equivalent levels were derived based on upper end
      (32.5 g/d) and average (7.5 g/d) estimates of shellfish consumption,
      respectively. Composite samples of oysters, clams, and mussels (15-20 per
      composite) were collected from target areas and analyzed for PAHs by gas
      chromatography/mass spectroscopy (GC/MS). Carcinogenic PAHs were converted to
      total BaP equivalents (wet weight) and compared with criteria. Two oyster
      samples, collected from a slough off of Coos Bay, contained 33.9 and 34.5
      microg/kg BaP equivalents; all other samples had less than 10 microg/kg BaP
      equivalents. An evaluation of the PAH profiles in the two higher oyster samples
      indicated a primary source other than the New Carissa oil. Because shellfish
      sample BaP equivalents attributable to the New Carissa oil spill did not exceed
      10 microg/kg, shellfish harvesting was reopened on 4 March 1999. This study
      revealed some of the inherent difficulties in attempting to quantify health risks
      from contaminated shellfish following an oil spill and demonstrated the clear
      need for standardized protocols for responding to such events.

PMID- 10912587
TI  - Evaluation of the pharmacokinetic interactions between orally administered
      trihalomethanes in the rat.
AB  - The blood kinetics of trihalomethanes has recently been reported to differ
      between an oral administration of any single trihalomethane (0.25 mmol/kg) [THMs:
      chloroform, bromoform, bromodichloromethane (BDCM), dibromochloromethane (DBCM)]
      and a combined administration of 0.25 mmol/kg of each of the 4 THMs. The
      significant increase in blood concentrations of THMs could be a consequence of
      pharmacokinetic interactions between two or more of the THMs present
      simultaneously. The objective of the present study was to characterize the blood
      kinetics of THMs following oral administration singly or as binary mixtures in
      order to assess the relative contribution of each THM to the kinetic
      interferences observed with the quaternary mixture. A single dose of each THM
      (0.5 mmol/kg) alone or of a binary mixture containing 0.5 mmol/kg of each THM was
      administered by gavage to male Sprague-Dawley rats. The venous blood
      concentrations of unchanged THMs were measured for up to 720 min
      postadministration by headspace gas chromatography. Results showed that, compared
      to single administration, each binary mixture caused a significant increase in
      the blood concentrations of both THMs present and this effect increased with
      time. The impact, however, was not similar for each mixture, especially during
      the first hour following administration of the compounds (bromoform and DBCM).
      Among the four THMs, bromoform and DBCM kinetics appeared to be more sensitive to
      the mixture effect and to exert the greatest impact on the kinetics of the second
      THM present in the mixture. Simulation exercises conducted with physiologically
      based toxicokinetic models suggest metabolic inhibition as the possible mechanism
      of the interaction between THMs. In conclusion, the results of this study show
      that, at the dose level investigated, every binary combination of THMs, when
      orally administered, resulted in a significant modulation of their
      pharmacokinetics and suggest that this is probably the consequence of a mutual
      metabolic inhibition between the THMs.

PMID- 10912586
TI  - Effects of inhaled 1,1,1-trichloroethane on the regional brain cyclic GMP levels
      in mice and rats.
AB  - As it is known that volatile organic compounds (VOCs) exhibit differential
      dispositions among anatomically discrete brain regions in rodents as well as in
      humans, potential toxicological consequences of this pharmacokinetic feature were
      evaluated using measurements of cyclic GMP (glucose monophosphate). With the
      knowledge of 1, 1, 1-trichloroethane (TRI) uptake and distribution in the various
      brain regions, cyclic GMP was evaluated due to (1) known susceptibility to the
      effects of organic solvents, (2) pivotal physiological role in perpetuating
      changes in neurochemical pathways, and (3) possible involvement with
      neurobehavioral functions, whose disruption is one of the primary health effects
      associated with solvent exposures. Male CD-1 mice and Sprague-Dawley rats inhaled
      5000 ppm TRI for 40 and 100 min in dynamic inhalation exposure chambers, and the
      brain was procured from the animals immediately following termination by
      microwave irradiation. After 40 min of TRI inhalation, significant decreases in
      cyclic GMP levels were found in the cerebellum of both species, 55% and 58%,
      respectively, relative to the controls. There was a further decrease in both
      species after 100 min of TRI inhalation. Smaller decreases in cyclic GMP were
      seen in the cortex of both species at both time points of measurement. A decrease
      in cyclic GMP was observed in the medulla oblongata of mice but not in rats after
      40 min of exposure. Due to its signal transduction functions, it might be
      expected that the effects of TRI on cyclic GMP levels could directly impact
      neurological function. Comparison of the results from this study with the
      regional brain distribution of TRI and its effects on behavioral performance seen
      in previous studies by this laboratory appeared to indicate that alterations in
      brain cyclic GMP levels are only involved with the neurobehavioral toxicity of
      TRI in an indirect fashion; consequently, behavioral effects and decreases in
      cyclic GMP do not appear to be directly related to regionally differential
      dispositions of TRI in rodent brain.

PMID- 10912588
TI  - Comparison of synthetic zeolite catalysts and alumina binders administered
      intratracheally to rats.
AB  - An intratracheal (IT) screening assay was performed in rats on a series of
      aluminosilicate catalysts (synthetic zeolites) and alumina binders to compare
      their relative ability to cause pulmonary fibrosis and related changes. Before
      initiation of IT screens, both the uniformity of deposition and residence time of
      a prototype catalyst in the lung were determined. Subsequently, the test
      materials were instilled and animals were evaluated 6 mo later for lung volumes,
      pulmonary pressure-volume curves, pulmonary hydroxyproline (OHPro) content, lung
      weights, and histopathology. Negative controls were saline and glass beads; the
      positive control was quartz. The test materials were organic-free ZSM-5 crystals,
      organic form of ZSM-5 crystals, alumina-bound ZSM-5, nickel/ZSM-5/ Al2O3 binder,
      used nickel/ZSM-5/Al2O3 binder, nickel-tungsten/ZSM-5/Al2O3 binder, and Bayer
      pseudoboehmite. For each, groups of 12 male rats were dosed once with either 25
      or 50 mg of ground particles (> or =95% less than 2.4 microm). Second to quartz,
      the sample of alumina caused the most pronounced pulmonary reactions at 6 mo
      after dosing. Therefore, the effects of four aluminas were subsequently compared
      (Bayer pseudoboehmite, Bayer gammaAl2O3, Ziegler pseudoboehmite, and Ziegler
      gammaAl2O3). The results support the idea of a lack of long-term effects from
      exposure to normal concentrations of these materials in the workplace. Also, the
      IT assay proved to be a very useful tool for ranking the relative effects of this
      series of zeolites and aluminas.

PMID- 10912589
TI  - Comparison of rhyming and word generation with FMRI.
AB  - Functional magnetic resonance imaging (FMRI) has been successfully used to non
      invasively map language function, but has several disadvantages. These include
      severe motion sensitivity, which limits overt verbal responses in behavioral
      paradigms, such as word generation. The lack of overt responses prevents
      behavioral validation, making data interpretation difficult. Our objective was to
      compare the FMRI activation patterns of a novel silent rhyme determination task
      requiring a non-verbal response, to covert word generation from visually
      presented letters. Five strongly right-handed subjects performed both tasks
      during multi-slice coronal echo-planar T2*-weighted FMRI. Single subject
      activation maps were generated for each task by correlation analysis of single
      pixel time series to a boxcar reference function. These maps for the two tasks
      were separately interpolated to 256(3), transformed into Talairach space, summed,
      and thresholded at t>6. Combined activation maps from both tasks showed similar
      robust perisylvian language area activation, including inferior frontal gyrus,
      posterior superior temporal lobe, and fusiform gyrus. Subjects performed well on
      the rhyming task, which activated left hemisphere cortical regions more
      selectively than the word generation task. The rhyming task showed less
      activation than the word generation task in areas typically not considered
      specifically related to language function, such as the dorsolateral prefrontal
      cortex and anterior cingulate. The rhyming task is a useful tool for brain
      mapping and clinical applications, potentially more specific to cortical language
      areas than verbal fluency.

PMID- 10912590
TI  - Modulation and task effects in auditory processing measured using fMRI.
AB  - Active listening has been reported to elicit a different sensory response from
      passive listening and is generally observed as an increase in the magnitude of
      activation. Sensory activation differences may therefore be masked by the effect
      of attention. The present study measured activation induced by static and
      modulated tones, while controlling attention by using target-discrimination and
      passive listening tasks. The factorial design enabled us to determine whether the
      stimulus-induced activation in auditory cortex was independent of the information
      processing demands of the task. Contrasted against a silent baseline, listening
      to the tones induced widespread activation in the temporal cortex, including
      Heschl's gyrus (HG), planum temporale, superior temporal gyrus (STG), and
      superior temporal sulcus. No additional auditory areas were recruited in the
      response to modulated tones compared to static tones, but there was an increase
      in the response in the STG, anterior to HG. Relative to passive listening, the
      active task increased the response in the STG, posterior to HG. The active task
      also recruited regions in the frontal and parietal cortex and subcortical areas.
      These findings indicate that preferential responses to the changing spectro
      temporal properties of the stimuli and to the target-discrimination task involve
      distinct, non-overlapping areas of the secondary auditory cortex. Thus, in the
      present study, differences in sensory activation were not masked by the effects
      of attention.

PMID- 10912591
TI  - Automated Talairach atlas labels for functional brain mapping.
AB  - An automated coordinate-based system to retrieve brain labels from the 1988
      Talairach Atlas, called the Talairach Daemon (TD), was previously introduced
      [Lancaster et al., 1997]. In the present study, the TD system and its 3-D
      database of labels for the 1988 Talairach atlas were tested for labeling of
      functional activation foci. TD system labels were compared with author-designated
      labels of activation coordinates from over 250 published functional brain-mapping
      studies and with manual atlas-derived labels from an expert group using a subset
      of these activation coordinates. Automated labeling by the TD system compared
      well with authors' labels, with a 70% or greater label match averaged over all
      locations. Author-label matching improved to greater than 90% within a search
      range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search
      utility was evaluated using individual activations from the M1 mouth region (30
      subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4
      & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the
      TD system's overall match with authors' labels (90%) was better than that of the
      expert group (80%). When used in concert with authors' deeper knowledge of an
      experiment, the TD system provides consistent and comprehensive labels for brain
      activation foci. Additional suggested applications of the TD system include
      interactive labeling, anatomical grouping of activation foci, lesion-deficit
      analysis, and neuroanatomy education.

PMID- 10912592
TI  - Effect of pentobarbital on visual processing in man.
AB  - To investigate the effect of sedative agents on visual processing in humans, we
      analysed the BOLD contrast signal response to a visual stimulation paradigm in 15
      healthy, adult volunteers using functional magnetic resonance imaging. The
      subjects were tested during alert state and under sedation following intravenous
      administration of pentobarbital. The injection of pentobarbital not only
      significantly reduced the response signal strength but the reduction in BOLD
      contrast signal was related to the ratio of amount of sedative administered and
      the subject's body weight. The three subjects with the highest relative sedative
      dosage even displayed an inverted (negative) BOLD contrast signal. A significant
      reduction in the number of positively correlating pixels was found 15 min after
      administration of pentobarbital. All measured parameters returned to near pre
      sedative levels by the end of the experimental session. The relative dosage
      dependence of the strength of the BOLD signal the negative BOLD signal in the
      three subjects with the highest relative sedative dosage indicates that
      pentobarbital had a more pronounced effect on cerebral blood flow than on
      cerebral oxidative metabolism.

PMID- 10912593
TI  - A new vibrotactile stimulator for functional MRI.
AB  - Presenting various stimuli in an MRI scanner can be difficult due to the high
      magnetic field associated with the scanner. Mechanical vibration stimuli are
      difficult to deliver to subjects in the MRI environment because most vibration
      devices contain internal circuitry that can adversely interact with the high
      magnetic field. Piezoelectric ceramics can provide a solution to this problem
      since they do not require any internal circuitry to vibrate. Piezoceramics are
      nonmagnetic and they can be made to vibrate if supplied with an alternating
      current from a straight wire. We designed a piezoceramic vibrotactile stimulator
      that is safe and effective in functional MRI experiments. The stimulator was
      tested in an fMRI experiment at 35 and 150 Hz. The results yielded activation
      sites in the primary sensory cortex and Brodmann area 40 at both frequencies.

PMID- 10912594
TI  - What's new in the diagnosis and treatment of juvenile rheumatoid arthritis.

PMID- 10912595
TI  - Focal fibrocartilaginous dysplasia of long bones: report of eight additional
      cases and literature review.
AB  - We report eight additional cases of focal fibrocartilaginous dysplasia (FFCD) in
      the proximal tibia (five), distal ulna (one), and distal femur (two).
      Spontaneous, complete resolution of the lesion was observed in two tibiae and one
      ulna. Three tibial lesions with genu varum deformity were managed with osteotomy.
      Two femoral FFCDs caused persistent or progressive deformity: one genu valgum
      with patellar dislocation, and one genu varum. These patients underwent
      concomitant deformity correction and lengthening by the Ilizarov method. The
      final results were satisfactory in all patients except one, who underwent valgus
      tibial osteotomy and developed mild postoperative genu valgum. The analysis of a
      total of 46 cases in the literature and our experience suggests that (a) FFCD has
      a wide histopathologic spectrum, ranging from purely dense, fibrous tendon-like
      tissue to benign fibrocartilaginous tissue; (b) at least 45% of tibial FFCD
      demonstrates progressive, spontaneous resolution; (c) in contrast, femoral and
      humeral FFCDs appear to have a slim possibility of spontaneous regression of the
      deformity; and (d) corrective osteotomy is indicated when the deformity is
      increasing or persistent, or when the existing deformity is severe enough to
      jeopardize adjacent joint mechanics and alignment.

PMID- 10912596
TI  - Wedge-shaped distal tibial epiphysis in the pathogenesis of equinovalgus
      deformity of the foot and ankle in tibial lengthening for fibular hemimelia.
AB  - Fibular hemimelia is associated with an equinovalgus deformity of the foot and
      ankle and different degrees of wedging of the distal tibial epiphysis. This
      deformity is often a major problem during lengthening of the shortened tibia. To
      determine the significance of the wedge-shaped distal tibial epiphysis in the
      pathogenesis of the equinovalgus deformity of the foot and ankle during and after
      lengthening, we reviewed 20 patients who had undergone tibial lengthening by
      either the Wagner or the Ilizarov technique. The mean duration of follow-up after
      removal of the fixator was 5.2 years (range, 2.3-9.7 years). Three types of wedge
      shaped distal tibial epiphyses were identified. A mildly wedged (type I)
      epiphysis was found in seven patients, a moderately wedged (type II) epiphysis
      was found in seven patients, and a severely wedged (type III) epiphysis, in six
      patients. Premature fusion of the lateral part of the distal tibial physis and
      growth retardation of the tibia were common after lengthening in patients with
      the type II or type III epiphysis. After lengthening, all patients with a type II
      or type III epiphysis had a recurrence or aggravation of foot deformities that
      existed before lengthening. This usually necessitated various secondary operative
      procedures to obtain a plantigrade foot. We believe that after lengthening, one
      should anticipate varying degrees of mild growth retardation and minimal foot
      deformity in patients with type I epiphysis, worsened asymmetric growth
      retardation and progressive foot deformity in patients with type II epiphysis,
      and severe growth retardation and severe foot deformity in patients with type III
      epiphysis.

PMID- 10912597
TI  - Motor milestones in children with diastrophic dysplasia.
AB  - Diastrophic dysplasia (DD), an autosomal recessive skeletal dysplasia, results in
      short-limbed short stature, generalized joint dysplasia, and spinal, hand, foot,
      and ear deformities. Children with DD experience both growth and motor
      developmental delays. To quantify the motor developmental delays, data on motor
      milestone attainment and other important characteristics were collected by
      retrospective questionnaire on 25 individuals with DD. Means and standard
      deviations were calculated for time to motor milestone attainment and are
      presented with minimum, maximum, 25th, 50th, 75th, and 90th percentile values.
      Percentages of individuals who could perform daily living and recreational tasks
      were tabulated. The mean times to milestone attainment for children with DD are
      all significantly longer than published means for nonaffected children. Notably,
      children with DD roll over at 5.2 +/- 2.2 months, sit unsupported at 8.3 +/- 2.3
      months, pull up to a stand at 13.5 +/- 5.8 months, and walk at 24.4 +/- 9.2
      months. The data presented here should be useful as preliminary reference
      standards for motor milestone attainment in children with DD.

PMID- 10912598
TI  - Scleroderma in childhood: a 35-year history of cases and review of the
      literature.
AB  - Scleroderma is a connective tissue disease with a variety of clinical
      presentations. The purpose of our study was to review representative cases of
      scleroderma in childhood to determine the initial presentation, course of the
      disease, orthopaedic manifestations, and the necessity and success of surgical
      intervention. Records from the four medical centers were retrospectively reviewed
      to identify the patients who were diagnosed with scleroderma over the past 35
      years. Data on disease presentation, course, treatment, and response were
      collected. Seventeen cases representing the variety of clinical presentations are
      presented. Scleroderma characteristically presents with asymmetric lesions
      involving the extremities and remains a diagnostic and therapeutic challenge.
      Treatment must be individualized to the patient and his or her specific
      limitations brought about by the disease. Early diagnosis, supportive care, and
      physical therapy combined with early orthopaedic surgical intervention to release
      joint contractures are among the most efficacious treatments.

PMID- 10912599
TI  - Inverted arcuate osteotomy and external fixation for adolescent tibia vara.
AB  - The purpose of our review is to describe and report results of a surgical
      technique for the treatment of adolescent Blount's disease. We retrospectively
      reviewed the results of 15 inverted arcuate osteotomies combined with external
      fixation. The inverted arc provides a proximal and stable osteotomy that can
      correct deformity in three planes. External fixation provides stable fixation,
      access to surgical wounds, and postoperative adjustment. According to the
      criteria of Schoenecker, we had 80% good results. Two patients with poor results
      were the most overcorrected, suggesting that overcorrection may not be so
      desirable as once suggested. We conclude that the inverted arcuate osteotomy with
      external fixation is an effective, reliable, and simple technique for treating
      adolescent tibia vara.

PMID- 10912600
TI  - Prognostic evaluation of Legg-Calve-Perthes disease by MRI. Part I: the role of
      physeal involvement.
AB  - Twenty-eight unselected hips affected by Legg-Calve-Perthes disease (LCPD) in 24
      patients from 1987 to 1994 had magnetic resonance imaging (MRI) performed. The
      patients were retrospectively reviewed at a mean follow-up of 5.4 years. An
      interobserver blind analysis was made to establish the reliability of four MRI
      parameters: extent of epiphyseal necrosis (EXT), lateral extrusion of the femoral
      head (LAT), physeal involvement (PHY), and metaphyseal changes (MET). The
      interobserver analysis resulted in a good reliability for all MRI parameters
      (concordance, >80%; K index, >0.45). A statistical correlation study (Spearman
      test) was then done between each MRI parameter and the condition of the hips at
      follow-up evaluated by Stulberg class and a personal scored system (total score)
      of clinical-radiographic condition. All MRI parameters appeared well correlated
      to the Stulberg class and to the total score (S > 0.66; p < 0.05). PHY resulted
      the strongest correlated parameter (S = 0.84 for Stulberg class; S = 0.91 for
      total score). Finally our statistical correlation study demonstrates physis
      involvement to have a high predictive value in LCPD; therefore it can be assumed
      as the main risk factor in formulating prognosis.

PMID- 10912601
TI  - Prognostic evaluation of Legg-Calve-Perthes disease by MRI. Part II:
      pathomorphogenesis and new classification.
AB  - The most widely used system of grading Legg-Calve-Perthes disease (LCPD) is still
      the radiographic grouping by Catterall, although it lacks interobserver
      reliability, especially in the early stages. The predictive value of Salter
      Thompson classification and Herring's "lateral pillar" classification are still
      being studied. In Part 1, we demonstrated the good reliability and the predictive
      value of four magnetic resonance imaging (MRI) indices (extension of necrosis,
      lateral extrusion, physeal involvement, metaphyseal changes) through their
      correlation to clinical and radiographic conditions of the hips at follow-up. The
      same good results were obtained by submitting to statistical analysis a second
      group of 31 patients (French series). On the basis of these statistical studies,
      a new classification has been proposed. It takes into account the extent of
      necrosis and two MRI risk signs: lateral extrusion and physeal involvement. The
      extent of necrosis up to or more than 50% separates two main groups, A and B. The
      associated MRI risk factors distinguished six classes with different prognoses.
      Appropriated treatment also is suggested for each class. Our experience on MRI in
      LCPD led us to draw a pathomorphogenetic model called "packed capsule." According
      to this biomechanical model, the femoral head is considered a segment of a sphere
      made of viscoelastic material and hermetically sealed. The deformation of the
      head depends on the behavior of the necrotic fluid collected inside the capsule
      under the weight-bearing forces. Finally, our suggestion in the treatment of
      Perthes disease is to relieve weight bearing up to the fragmentation stage,
      whether the diagnosis has been made by the use of MRI or without it. During the
      fragmentation stage, MRI is extremely useful in performing prognosis; at this
      time our classification can be applied, and the corresponding treatment can be
      followed.

PMID- 10912602
TI  - The effect of prereduction traction on the results of closed reduction of
      developmental dislocation of the hip.
AB  - A group of 86 developmentally dislocated hips in children aged 6-48 months was
      treated by closed reduction before 1957 without preliminary traction, and another
      group of 176 hips was treated after 1957 with prereduction traction. The results
      in these two groups were compared to clarify the effect of prereduction traction.
      During the treatment of these cases, subcutaneous adductor tenotomy was performed
      when obviously indicated. Otherwise preliminary traction was the only variable
      between the two groups. To rule out tenotomy as a factor influencing the result,
      the hips of children aged 6-36 months who had prereduction traction as the single
      variable were taken out of the group and the results analyzed. It is concluded
      that prereduction traction decreases the incidence of avascular necrosis of the
      femoral head when developmentally dislocated hips of children aged 6-36 months
      are treated with closed reduction with traction as the single variable.

PMID- 10912603
TI  - Femur shaft fractures in toddlers and young children: rarely from child abuse.
AB  - One hundred thirty-nine children younger than 4 years were identified
      retrospectively from the period of 1993 through 1997 to have an isolated fracture
      of the shaft of one or both femurs. Abuse was classified as group A (definite,
      likely, or questionable abuse) or group B (unknown cause, questionable accident,
      likely accident, or definite accident). The average age of the children was 2.3
      +/- 1.1 years. Thirteen children, 9% of the total group, average age of 1.1 +/-
      1.0 years, were likely to have been abused (group A). A total of 126 children,
      91% of the total, average age 2.3 +/- 1.0 years, sustained their fracture most
      likely as a result of an accident (group B). Whether a child had not yet achieved
      walking age (toddler) was the strongest predictor of likely abuse. Ten (42%) of
      24 of nonwalking children were in group A, whereas only three (2.6%) of 115 of
      walking children were in group A (p < 0.001). Child Protective Services may have
      been unnecessary in 42-63% of cases. Unless other evidence of abuse such as an
      inconsistent story, bruises, or other fractures are present, abuse is very
      unlikely to be involved in the walking-age child, analogous to the toddler
      fracture of the tibia.

PMID- 10912604
TI  - Intramedullary nailing of femoral fractures in adolescents.
AB  - Fifty femoral shaft fractures were treated with reamed, interlocking,
      intramedullary nails utilizing a greater trochanteric starting point from 1991
      through 1998. The 17 girls and 31 boys ranged in age from 10 to 16 years (mean,
      13.2 years) at the time of injury. Average follow-up after fracture was 16
      months. All fractures united, and the average leg-length discrepancy was 1 mm
      (range, -10 mm to +11 mm). No patient had angular or rotational deformities. No
      patients developed osseous necrosis of the femoral head. Despite intramedullary
      nailing through the greater trochanteric apophysis, articulotrochanteric distance
      measurements increased only 4.5 mm at the time of last follow-up. No patient
      developed significant proximal femoral deformity with some follow-up as far as 60
      months from the time of surgery. Intramedullary nailing through a trochanteric
      starting point is a safe, effective method for treating femur fractures in this
      adolescent age group.

PMID- 10912605
TI  - A technique to determine proper pin placement of crossed pins in supracondylar
      fractures of the elbow.
AB  - Supracondylar humerus fractures are the most common elbow injury in children.
      Stable fractures can be closed, reduced, and casted, whereas unstable fractures
      require percutaneous pinning. Studies have shown that there is a biomechanical
      advantage of crossed pin fixation as opposed to two lateral pin fixation.
      However, medial pin placement has the risk of injuring the ulnar nerve. This
      modification of technique was used on 46 patients, aged 12 months to 14 years
      (median age, 3.6 years). Two patients had an ulnar sensory and motor neurapraxia,
      and two patients had cubitus varus deformities postoperatively. Thus, a safe,
      easy, and reproducible technique of crossed pin fixation is described here.

PMID- 10912606
TI  - Wrist arthrodesis in children with cerebral palsy.
AB  - Wrist arthrodesis was performed on 19 upper extremities in 18 children with
      cerebral palsy to correct volar flexion and ulnar deviation deformities. Mean age
      at the time of surgery was 15.8 years, and mean follow-up was 4.7 years. Review
      of medical records and radiographs and follow-up clinical examination, including
      standardized functional testing and a child/parent questionnaire, were performed
      to assess outcome in technical, functional, and satisfaction domains. Technical
      domain outcomes were best when arthrodesis was performed by proximal row
      carpectomy with plate fixation. Functional improvement, as documented by the
      House scale, averaged 1.8 levels, with 14 children (83.3%) showing improvement.
      Child/parent satisfaction with cosmetic, hygienic, and functional outcomes was
      high, ranging from 72 to 94%. Wrist arthrodesis, when combined with appropriate
      procedures for the forearm, fingers, and thumb, provided excellent technical,
      functional, and satisfaction domain outcomes for children with cerebral palsy,
      particularly those with more severe upper extremity involvement, dyskinetic type
      cerebral palsy, or poor motivation for rehabilitation.

PMID- 10912607
TI  - Changes in gait at 1 year post-selective dorsal rhizotomy: results of a
      prospective randomized study.
AB  - We performed a prospective randomized trial to compare the effects of selective
      dorsal rhizotomy with intensive physical therapy to intensive physical therapy
      alone in a group of children with mild spastic diplegic cerebral palsy.
      Instrumented gait analysis was carried out upon enrollment into the study and
      after 1 year. Changes in ambulatory status, time/distance parameters, and gait
      kinematics were observed for both groups. Considerable variability was present in
      both groups. Changes in ankle dorsiflexion, foot progression angle, and hip and
      knee extension in stance were significantly better in the selective dorsal
      rhizotomy group compared to the physical therapy group at 1 year (p < 0.05).
      These differences were not associated with significant improvements in functional
      gait as determined by changes in time/distance parameters or ambulatory status.

PMID- 10912608
TI  - Lateral column lengthening as treatment for planovalgus foot deformity in
      ambulatory children with spastic cerebral palsy.
AB  - The purpose of this study was to investigate the effectiveness of lateral column
      lengthening in the treatment of flexible, planovalgus foot deformity of
      ambulatory children with spastic cerebral palsy (CP). Fifteen ambulatory children
      (23 feet) with spastic CP and flexible planovalgus foot deformities received
      lateral column lengthenings through the calcaneus or calcaneocuboid joint. At an
      average of 4.1 years of follow-up (minimum, 2.3 years), 17 (74%) feet had good,
      two (9%) had fair, and four (17%) had poor outcomes. Poor outcomes resulted from
      recurrence of deformity. Improvements in preoperative, postoperative, and follow
      up radiographic measurements were found. However, these improvements are not
      related to the clinical outcomes. Calcaneal lengthening is a successful treatment
      for flexible planovalgus foot deformity in ambulatory children with spastic CP.
      The high failure rate is a significant limitation to the procedure. Further
      investigation of the objective measurement of planovalgus foot deformity is
      needed.

PMID- 10912609
TI  - In situ posterolateral spine arthrodesis for grades III, IV, and V
      spondylolisthesis in children and adolescents.
AB  - The purpose of the study was to analyze the results after in situ posterolateral
      arthrodesis without reduction in children and adolescents with Meyerding grades
      III and IV spondylolisthesis and in patients with spondyloptosis who had an
      average follow-up of 12.8 years. The study population consisted of 21 patients
      who underwent an in situ posterolateral spinal fusion from L4 to S1 with
      autogenous iliac bone graft and were immobilized in a pantaloon cast for 4
      months. All patients reported improvement after the operation and had no
      limitation in daily activities. Only four of 21 patients complained of occasional
      mild pain after physical activity, which resolved with rest and did not disturb
      their work. After surgery there were no motor deficits, incontinence of bowel or
      bladder, or sexual dysfunction. Roentgenographic findings showed progression of
      the slip in five patients and increase of the slip angle and the displacement
      index in two patients. These changes happened during the first year after the
      operation. Progression of the slip was not associated with symptoms. There was no
      pseudarthrosis. In situ posterolateral arthrodesis with a large amount of
      autogenous bone graft followed by immobilization in a pantaloon cast yields a
      solid arthrodesis and provides satisfactory results.

PMID- 10912610
TI  - Relationship between Quantec measurement and Cobb angle in patients with
      idiopathic scoliosis.
AB  - The Quantec Spinal Imaging System (QSIS) is a raster stereography used to measure
      three-dimensional trunk images. The Q angle, a coronal plane measurement
      generated by the Quantec Spinal Imaging System (QSIS), was compared with the Cobb
      angle in assessment of scoliosis curve magnitude. One hundred forty-nine patients
      with idiopathic scoliosis were evaluated using both the Quantec system and plane
      radiographs. The Cobb and Q angles demonstrated significant correlation in the
      thoracic region (r = 0.65, p < 0.05), lumbar region (r = 0.63, p < 0.05), and in
      the thoracolumbar region (r = 0.70, p < 0.05). The difference between the Q and
      Cobb angles was small when the Cobb angle was <21 degrees with less than 6
      degrees of axial surface rotation, as measured by the QSIS method. For smaller
      curves with minimal rotation, there is close correlation between the Cobb angle
      and the Quantec angle.

PMID- 10912612
TI  - Evaluation of the hemi-Cincinnati incision for posteromedial soft-tissue release
      in clubfoot.
AB  - Posteromedial soft-tissue release operations were performed on 42 idiopathic
      clubfeet in children younger than 2 years of age through the medial half of the
      Cincinnati incision (the hemi-Cincinnati incision). This incision gave adequate
      exposure to all structures to be released. Wound closure was possible in all 42
      feet without having to hold the foot in plantarflexion or inversion. Wound
      healing was satisfactory in the majority of instances and 81% of the scars,
      assessed 9 months after the operation, were graded as excellent or good. The scar
      is located in an area of the foot that can be concealed easily and should a more
      radical soft-tissue operation be needed later, the same incision can be extended
      easily. The authors recommend this incision as the incision of choice for
      performing posteromedial soft-tissue release operations on clubfeet in children
      younger than 2 years of age.

PMID- 10912611
TI  - The functional outcome of staged surgery for the correction of talipes
      equinovarus.
AB  - Between 1988 and 1995, 110 idiopathic clubfeet from a cohort of 120 recalcitrant
      feet in 86 patients requiring surgical treatment were studied. There were 61 male
      and 25 female patients. The mean age at surgery was 9.5 months. In 91 feet, the
      surgery consisted of an initial plantarmedial release, followed 2 weeks later by
      a posterolateral release. Nineteen feet required only a posterolateral release.
      Feet were categorised preoperatively and prospectively according to a system
      suggested by Dimeglio into four groups, and the rates of relapse and wound
      healing data were previously reported. This paper reports the functional outcome
      of this cohort of idiopathic clubfeet and the results are related to the
      preoperative grade, the patient's gender, the age at which the child first
      walked, and whether the deformity is unilateral or bilateral. The interim
      functional outcome is good in the majority of cases despite a high rate of
      relapse in the more severe deformities.

PMID- 10912613
TI  - Predictive value of intraoperative clubfoot radiographs on revision rates.
AB  - The predictive value of intraoperative radiographic assessment and its
      correlation with short term revision rates is presented for surgical correction
      of resistant clubfoot. Seventy-three children (115 feet) who underwent a primary
      procedure at one institution for idiopathic clubfoot between January 1991 and
      December 1994 were reviewed. A strategy using sequential release guided by
      intraoperative radiographs was employed in all cases. The intraoperative
      radiographic findings correlated with the need for early revision surgery, with
      residual radiographic evidence of cavus deformity associated with the greatest
      risk for revision. The sequential release strategy resulted in fewer
      overcorrections compared with historical controls of more complete subtalar
      release.

PMID- 10912614
TI  - A preliminary report of the use of botulinum toxin type A in infants with
      clubfoot: four case studies.
AB  - This report describes the use of botulinum toxin type A (BTX-A) in four infants
      with very severe clubfoot deformity. The gastrocnemius and posterior tibial
      muscles were injected with BTX-A after the patients reached a treatment plateau
      in physical therapy. Significant improvement in foot dorsiflexion and foot
      flexibility was seen in two patients, and surgery was not required. Surgical
      intervention was necessary in the remaining two patients, both of whom were
      ultimately diagnosed with a demyelinating neuropathy. The use of botulinum toxin
      as an adjunct to conservative care in infants with clubfoot is discussed.

PMID- 10912615
TI  - Pyogenic spondylitis and early tuberculous spondylitis in children: differential
      diagnosis with standard radiographs and computed tomography.
AB  - In a study of 23 patients, axial computed tomography (CT) was the most valuable
      modality to differentiate between early tuberculous (10 patients) and pyogenic
      spondylitis (13 patients). Tuberculous spondylitis showed large erosions with
      calcification, whereas pyogenic spondylitis showed multiple small well-defined
      erosions, mostly without calcification. Both groups had large or small
      paravertebral soft tissue swelling, with accompanying calcification, in six of
      the 10 patients with tuberculous spondylitis and in only one patient with
      pyogenic spondylitis. Tuberculous spondylitis showed larger intraspinal
      extradural abscesses, with calcification in 50% of cases, whereas pyogenic
      spondylitis demonstrated no calcification.

PMID- 10912616
TI  - Epiphyseal separations after neonatal osteomyelitis and septic arthritis.
AB  - Complete separation of an epiphysis is a rare complication of neonatal
      osteomyelitis and septic arthritis. We report two cases of pathologic epiphyseal
      separation after neonatal osteomyelitis, involving the distal and proximal
      femoral epiphyses with a follow-up of 2 and 7.5 years, respectively. Birth
      trauma, scurvy, and nonaccidental injury should be considered in the differential
      diagnosis of pathologic epiphyseal slip. The pitfalls in diagnosis are many, and
      plain radiograms of unossified epiphyses are often misleading. A high index of
      suspicion and the use of imaging modalities are useful in making an early
      diagnosis of epiphyseal slip. The optimal treatment is controversial, and the
      long-term prognosis is uncertain. The potential for recovery appears to be
      excellent, provided an early diagnosis is made and prompt treatment by anatomic
      reduction of the displaced epiphysis is instituted.

PMID- 10912617
TI  - Three-dimensional structures of MHC class I-peptide complexes: implications for
      peptide recognition.
AB  - Over the last decade, the number of crystal structures of major
      histocompatibility complex (MHC) class I-peptide complexes has increased rapidly.
      These studies have provided unique and fascinating insights into the structural
      basis of MHC-peptide interactions and the specificity of peptide recognition by
      MHC class I molecules.

PMID- 10912618
TI  - A burgeoning family of biological mediators: chemokines and chemokine receptors.
AB  - Chemokines are a superfamily of pro-inflammatory polypeptide cytokines that
      selectively attract and activate different cell types. Most of its members are
      small proteins that exhibit conserved cysteines in specific positions. Chemokines
      activate cells through their binding to shared or unique cell surface receptors
      which belong to the seven-transmembrane (STM), G-protein-coupled receptors
      (GPCRs). The large number of chemokines and chemokine receptors are indicative of
      the importance of these molecules in a variety of pathophysiological conditions.

PMID- 10912620
TI  - Beyond a structural component: sphingolipids in immunology.
AB  - Two major classes of lipids participating in signaling cascades in immune cells
      are known today. One comprises glycerol-based lipids with diacylglycerol as its
      most prominent member that mediates the activation of classical and novel protein
      kinase C molecules. The second group contains the sphingolipids, with the best
      investigated representatives being sphingosine, sphingosine-1-phosphate, and
      ceramide. In the last years the latter two molecules have especially received
      considerable attention for their modulatory capacity in the course of an
      apoptotic response. Today it is clear that sphingolipids are ubiquitously
      distributed in all eukaryotic cells, especially in cellular membranes, where they
      were previously thought to fulfil an exclusively structural role. Recent
      findings, however, have demonstrated functions beyond this. Sphingolipid specific
      G-protein coupled receptors were identified and their role as intracellular
      second messengers has been further elucidated. In addition, glycosphingolipids,
      in particular, are enriched in certain membrane compartments, known as detergent
      resistant membranes. These serve as entry sites for several receptor-mediated
      signaling events by stabilizing receptor/kinase interactions, suggesting an
      involvement in the initiation of signaling cascades. Altogether, these findings
      have led to new insights into both the role of these lipids in signaling as well
      as the underlying pathology of several diseases with imbalances in the
      sphingolipid metabolism. The development of these disorders has mainly been
      attributed to the toxic potential of lysosphingolipids up to now. In addition,
      attempts have been made to develop compounds and drugs containing the
      sphingolipid backbone for influencing diseases associated with unwanted cell
      activation (e.g, cancer, inflammatory processes). These novel findings and
      developments are reviewed in the following.

PMID- 10912619
TI  - Listeria monocytogenes as an alternative vaccine vector for HIV.
AB  - The necessity for an HIV vaccine and a brief review of current strategies towards
      this aim are given here to set into context contemporary studies towards
      exploiting the bacterium Listeria monocytogenes as an HIV vaccine vector. The
      cell biology and immunology of this unusual intracellular organism are also
      reviewed, in addition to its application to introducing viral antigens, including
      HIV antigens, to the immune system.

PMID- 10912621
TI  - Cytokine-producing T cell subsets in human leishmaniasis.
AB  - Leishmania specific Th1/Th2 cells have been identified in humans as well as in
      mice. There is a correlation between the clinical outcome of the infection and
      the cytokine response profile. Generally, the production of Th2 cytokines leads
      to severe infection, whereas the production of Th1 cytokines leads to subclinical
      or mild infections. In mice, an infection leads to a polarisation of either Th1
      or Th2 Leishmania antigen specific cells. In contrast, both Th1 and Th2
      Leishmania antigen specific cells can be identified in humans cured from L.
      donovani infections. Theoretically, Th1 cells and Th2 cells mutually down
      regulate each other. However, the presence of antigen specific regulatory T cell
      subsets may provide an environment that allows the presence of both Th1 and Th2
      cells.

PMID- 10912622
TI  - Current status and future perspectives of DNA vaccine delivery by attenuated
      intracellular bacteria.
AB  - Vaccination by intradermal or intramuscular injection of antigen-encoding plasmid
      DNA elicits strong cellular and humoral immune responses. Professional antigen
      presenting cells (APC) seem to induce these responses, making it, therefore,
      desirable to deliver the plasmid molecules directly to these cells. The
      exploitation of attenuated intracellular bacteria as DNA delivery vehicles makes
      the direct targeting of DNA vaccine vectors to professional APC feasible.

PMID- 10912623
TI  - Prospects for development of new antimycobacterial drugs, with special reference
      to a new benzoxazinorifamycin, KRM-1648.
AB  - In this article, I have thoroughly reviewed the status of development of new
      antimycobacterial drugs, in particular, rifamycin derivatives (rifabutin,
      rifapentine, and a new benzoxazinorifamycin, KRM-1648), fluoroquinolones
      (ciprofloxacin, ofloxacin, sparfloxacin, levofloxacin, gatifloxacin,
      sitafloxacin, moxifloxacin, and others), new macrolides (clarithromycin,
      azithromycin, roxithromycin), and others. In this review, I have mainly described
      the in vitro and in vivo activities of these drugs against Mycobacterium
      tuberculosis and atypical mycobacteria, especially Mycobacterium avium complex.
      In addition, therapeutic efficacy of these drugs in cases of clinical treatment
      of mycobacterial infections have also been briefly mentioned.

PMID- 10912624
TI  - Immune phenomena in echinoderms.
AB  - Advances in biochemistry and molecular biology have made it possible to identify
      a number of mechanisms active in the immune phenomena of echinoderms. It is
      obvious that echinoderms have the ability to distinguish between different
      foreign objects (pathologically changed tissues, microorganisms, parasites,
      grafts) and to express variable effector mechanisms which are elicited
      specifically and repeatably after a variety of non-self challenges. The molecular
      and biochemical basis for the expression of these variable defense mechanisms and
      the specific signals which elicit one type of effector mechanism are not,
      however, yet well known. The high capacity of coelomocytes to phagocytose, entrap
      and encapsulate invading microorganisms is a valid immune cell-mediated mechanism
      of echinoderms. The entrapped bacteria, discharged cellular materials and
      disintegrating granular cells are compacted and provoke the cellular
      encapsulation reaction. Moreover, humoral-based reactions form an integral part
      of the echinoderm defense system against microbial invaders. Factors such as
      lysozyme, perforins (hemolysins) vitellogenin and lectins are normal constituents
      of hemolymph, while cytokines are synthesized by echinoderms in response to
      infection.

PMID- 10912625
TI  - Circulating immune complexes in advanced Hodgkin's disease: qualitative analysis
      and prognostic significance.
AB  - The level of circulating immune complexes (CIC) may be a reflection of the
      underlying malignancy and appears to be related to the stage of disease, tumor
      burden and prognosis. Prognostic factors at diagnosis, clinical response,
      survival and CIC were analyzed in 89 patients with Hodgkin's disease. All
      patients were newly diagnosed, in advanced stage and treated with MOPP regimen.
      The median follow-up was 41 months. CIC were estimated by the polyethylene glycol
      precipitation test. The median age was 40 years and 52% were under the age of 45.
      Nodular sclerosis and mixed cellularity were the most common histologies, 36 and
      35% respectively. "B" symptoms were present in 65%, bulky disease in 29% and bone
      marrow involvement in 4% of the total. The erythrocyte sedimentation rate (ESR)
      was over 30 in 72% of patients and 27% had one or two extranodal localizations.
      Complete remission (CR) was obtained in 69 patients (77%). The only factor
      influencing the CR rate was the number of extranodal localizations (p<0.05). The
      ten-year relapse-free survival (RFS) and overall survival (OS) were 63 and 83%,
      respectively. RFS was adversely influenced by lymphocyte depletion histology
      (p=0.009) and by performance status over 1 (p=0.003). Elevated CIC levels were
      detected in 58% of the total. Patients with ESR over 30 had significantly higher
      values of CIC (p<0.05). Qualitative analysis of the CIC showed high levels of
      positivity to immunoglobulin G and M. C-reactive protein (CRP) was identified in
      42% of all samples. CRP is an acute phase protein which shows conformational
      similarity to the immunoglobulin molecule. There were no significant correlations
      between levels of CIC and the other prognostic factors. Survival was not
      influenced by the CIC level.

PMID- 10912626
TI  - Lymphoid aggregates in gastric biopsies: relationship to other mucosal lesions.
AB  - The purpose of this study is to estimate the prevalence of lymphocyte aggregates
      (precursor of MALT lymphomas) in gastric mucosal biopsies and to associate
      gastric lymphoid tissue with the age of patients, Helicobacter-associated
      gastritis and other gastric mucosal pathology. A consecutive series of gastric
      mucosal samples from 150 children and 256 adults were assessed for the presence
      of lymphoid aggregates as well as morphological characteristics, Helicobacter
      pylori status, signs of gastritis, mucosal atrophy and lymphoepithelial lesions.
      Fifteen selected samples with prominent lymphoid aggregates and 10 controls were
      examined immunohistochemically for the immunoglobulins A, G, M, lymphocytes B and
      T, clonality of B cell population, atypical lymphocytes and Epstein-Barr virus
      (EBV) antigen. There was an increase of H. pylori infection and mucosal lymphoid
      aggregates (MALT) rates in parallel with the increasing age of patients noted in
      the histological assessment of the mucosal samples. A close association of
      lymphoid aggregates with H. pylori infection and prominent active gastritis was
      found, but in adults with chronic non-active, particularly atrophic gastritis
      this association became weaker. No morphological and immunohistochemical signs of
      MALT lymphoma were present. Lymphoid aggregates in children were larger, with
      follicles, but less numerous and tended to be located in the intermediate and
      deeper parts of the gastric mucosa. Immunohistochemical studies showed an
      increase of IgA, IgM and lymphocytes T in the deeper part of the lamina propria
      in H. pylori-associated gastritis and lymphocyte T accumulation in the periphery
      of the lymphoid follicles. No evidence of monoclonality, CD31 positive
      lymphocytes or EBV antigen was detected. Lymphoid aggregates are related, but not
      exclusively, to H. pylori infection. Their detection rates achieve a peak in
      young adults with H. pylori infection. Lymphocytic aggregates are also present in
      chronic atrophic gastritis without H. pylori infection and may relate to
      autoimmune inflammatory response to other factors.

PMID- 10912627
TI  - Interleukin 1beta decreases the GSH content and catalase activity in the human
      peritoneal mesothelial cells in vitro.
AB  - The object of this study was to assess the effects of the inflammatory cytokine
      interleukin 1beta (IL-1beta) (0.01-1.0 ng/ml) on the activity of catalase (CAT),
      superoxide dismutase (SOD) and the level of glutathione (GSH), all being
      antioxidant mechanisms, in human peritoneal mesothelial cells (HPMC) in in vitro
      culture. HPMC were obtained from the omenta of nonuremic donors. The activity of
      the antioxidant mechanisms was studied on monolayers of HPMC, which were deprived
      of serum 48 h prior to experiment. The effect of the cytokine was tested in a
      medium with low serum concentration (0.1%) or in a medium with 10% fetal calf
      serum (FCS). Activity of the antioxidant mechanisms was determined by
      spectrophotometry. The GSH level was decreased in mesothelial cells (MC) after 24
      h of exposition to IL-1. However, after 72 h of incubation with IL-1 the GSH
      level increased in MC in the presence of 10% FCS, p<0.05. The activity of CAT was
      inhibited after 72 h exposure to IL-1. Interleukin 1 did not affect SOD activity
      in MC. However, when supplemented with 10% FCS, IL-1 decreased the activity of
      SOD after 24 and 72 h of incubation. We conclude that the activity of antioxidant
      mechanisms in MC is decreased by IL-1beta in ways that might increase their
      vulnerability to the cytotoxic effect of free radicals.

PMID- 10912628
TI  - Identification of blood group A and B antigens in human glycophorin.
AB  - Glycophorin A (GPA), the major sialoglycoprotein of human erythrocyte membranes,
      was isolated separately from blood group A and B erythrocytes using phenol-water
      extraction. After purification, performed as gel filtration in the presence of
      SDS, two glycophorin samples GPA-A and GPA-B were run, in duplicate, in SDS-PAGE
      and electroblotted onto Immobilon P. After staining with 1) anti-glycophorin
      antibody and 2) with relevant anti-blood group (A or B) antibody it was shown
      that the band pattern of the samples in each duplicate was the same. GPA-A and
      GPA-B samples were also degraded using Carlson degradation (beta-elimination in
      mild alkaline/strong reducing conditions) and from reaction products the
      fractions of O-glycans and N-glycans were isolated; they were used in
      hemagglutination inhibition test. It was shown that both sugar fractions derived
      from GPA-A did inhibit agglutination of blood group A erythrocytes by anti-A
      antibody, whereas oligosaccharide fractions derived from GPA-B inhibited
      agglutination of blood group B erythrocytes by anti-B antibody. These results,
      obtained using immunochemical methods, confirm the presence of blood group A and
      B determinants in the carbohydrate moiety of human glycophorin, derived from the
      blood group A or B erythrocytes, respectively.

PMID- 10912629
TI  - Diseases of the pleura: the use of talc for pleurodesis.
AB  - Talc either insufflated (poudrage) or in a suspension (slurry) is commonly used
      to create a pleurodesis in patients with recurrent pneumothorax or recurrent
      pleural effusions. There are now at least 32 cases in the literature in which
      patients developed the acute respiratory distress syndrome after receiving talc
      intrapleurally. The mechanism for the development of acute respiratory distress
      syndrome after the intrapleural administration of talc is not known, but it may
      be related to the systemic absorption of talc. Since there are effective
      alternatives to talc for producing pleurodesis (mechanical abrasion if
      thoracoscopy is performed; tetracycline derivatives or bleomycin if chest tubes
      are used), intrapleural talc should not be used to produce a pleurodesis.

PMID- 10912630
TI  - The use of adenosine deaminase and adenosine deaminase isoenzymes in the
      diagnosis of tuberculous pleuritis.
AB  - The bacillary population described in tuberculous pleuritis is small, and its
      most likely pathogenetic mechanism is essentially immunologic. This explains why,
      until now, the diagnostic identification of tuberculous pleuritis (TP) has been
      based on the presence of granulomas in pleural biopsy. Correcting this diagnostic
      deficiency through other parameters related to the specific pathogenetic
      mechanism has been widely studied. The determination of the levels of adenosine
      deaminase (ADA) in pleural fluid offers high performance in its discriminating
      capacity to identify TP (sensitivity 87 to 100%, specificity 81 to 97%).
      Adenosine deaminase expresses the sum of two isoenzymes (ADA1 and ADA2). ADA1 is
      ubiquitous in all cells, including lymphocytes and monocytes, whereas ADA2 is
      found only in monocytes. Analysis and determination of these isoenzymes have
      shown that ADA in TP increases particularly at the expense of ADA2 and that the
      ADA1 /ADAp activity ratio improves performance in terms of sensitivity,
      specificity, and efficacy (100%, 92 to 97%, and 98%, respectively) in correcting
      all false-negative and false-positive results except 1 to 9% of
      nonlymphoproliferative malignancies. Only the high performance of ADA in the
      identification of TP allows it to be assumed that pleural biopsy can be obviated,
      especially in patients aged less than 35 years of age or having a lymphocyte-to
      neutrophil proportion of more than 0.75 in regions of high prevalence. Quick
      determination and low cost justify its routine use in exudates. The ADA1 /ADAp
      activity ratio improves performance even more and could be used in cases with
      uncertain diagnoses or in regions with low prevalence of tuberculosis.

PMID- 10912631
TI  - Management of malignant pleural mesothelioma: a critical review.
AB  - Malignant mesothelioma remains a uniformly fatal disease and best supportive care
      continues to be the standard treatment. Neither chemotherapy nor surgery has been
      shown to prolong survival. Radiotherapy is not curative but is useful for
      prophylaxis against needle-track metastases and for symptom palliation.
      Combinations of therapies have been tried but most studies were uncontrolled and
      selection bias makes the results impossible to interpret. The combination of
      extrapleural pneumonectomy, chemotherapy, and radiotherapy attracted much
      interest, but the subsequent results were disappointing in a highly selected
      group of patients. Randomized controlled trials are desperately needed to provide
      definitive information on experimental treatments. It is also important to
      develop better measures of disease response and to assess quality of life issues
      in clinical trials. If patients are to receive therapies other than palliation,
      they should only do so in the setting of randomized controlled trials under
      approved protocols.

PMID- 10912632
TI  - Treatment of spontaneous pneumothorax.
AB  - Spontaneous pneumothorax (SP) continues to be a frequent management problem. The
      lack of universally accepted management guidelines and a myriad of treatment
      options contribute to the current heterogeneous approach to SP. Forthcoming
      guidelines may improve management. Meantime, simple observation in stable
      patients with a primary spontaneous pneumothorax (PSP) is reasonable, and
      encouraging smoking cessation is paramount. More aggressive management of a
      patient with a secondary spontaneous pneumothorax (SSP) is advisable and should
      include at least chest tube drainage with chest tube size selection key. Careful
      assessment of recurrence risk and early corrective intervention for patients with
      a persistent air leak will improve care of both PSP and SSP patients. If chest
      tube-directed pleurodesis is chosen for recurrence prevention, talc is the most
      successful agent available. However, no more than 5 g of talc should be utilized,
      given the potential increased risk for acute respiratory failure at higher doses,
      and patients should be advised of alternatives such as doxycycline. No
      overwhelming clinical outcome advantages for a thoracoscopic over a limited
      thoracotomy approach to SP management has been reported in any randomized
      controlled trial. Institutional experience with and the availability of
      thoracoscopy or limited thoracotomy should dictate the operative approach to SP
      recurrence prevention and air leak correction until further study clarifies the
      choice.

PMID- 10912633
TI  - A new look at old agents for pleurodesis: nitrogen mustard, sodium hydroxide, and
      silver nitrate.
AB  - In this review we analyze the evolution of pleurodesis. In spite of the fact that
      this procedure started in the beginning of the 20th century, the ideal sclerosing
      agent is not yet known. Emphasis is placed on the current tendency toward
      minimally invasive procedures in which insertion of catheters is favored over
      surgical procedures such as placement of chest tubes or thoracoscopy. Among the
      sclerosing agents, talc is preferred throughout the world. However, the possible
      development of acute respiratory distress syndrome, which is sometimes fatal,
      caused the awakening of interest in other drugs. Nitrogen mustard induces
      pleurodesis but causes important side effects. Sodium hydroxide and silver
      nitrate are effective and may be used in humans beings.

PMID- 10912634
TI  - Nontraumatic chylothorax.
AB  - Nontraumatic chylothorax is an uncommon condition of thoracic or abdominal origin
      caused by multiple disorders, of which malignancy is by far the most frequent
      one. Because gross appearance of pleural fluid is frequently misleading, pleural
      fluid and serum lipid analysis is required for its diagnosis. In addition to the
      presence of chylomicrons, chylothoraces are usually characterized by all three of
      the following: (1) a triglyceride level of more than 110 mg/dL; (2) a ratio of
      pleural fluid to the serum triglyceride level of more than 1.0; and (3) a ratio
      of the pleural fluid to serum cholesterol level of less than 1.0. In patients
      with lymphoma-related chylothorax refractory to chemotherapy and radiation
      therapy, medical thoracoscopic talc pleurodesis has an acceptable complication
      rate and a 100% success rate in the prevention of recurrences. Pleuroperitoneal
      shunting is considered a safe and effective treatment in the management of
      persistent chylothorax in children in the absence of chylous ascites.

PMID- 10912635
TI  - Disorders of pulmonary circulation: pulmonary vascular disease.

PMID- 10912636
TI  - Oral contraceptives and thrombosis.
AB  - Oral contraceptives (OCs) are used by many millions of healthy young women. Their
      ease of use and efficacy against unwanted pregnancy has made them an
      indispensable part of modern society. Despite various changes in formulation,
      they are clearly associated with an increased risk of venous thromboembolism
      (VTE). Case-control and prospective studies have developed a range of relative
      risks of VTE, but the important issue is the impact of VTE relative to perceived
      benefits of the OC. This involves societal as well as medical judgment. The
      development of third-generation OCs has led to considerable concerns that these
      newer preparations may be associated with additional thrombotic risks over and
      above those of the traditional second-generation preparations. The paradoxical
      effect, that a change in progestogen in the combined OC could lead to increased
      VTE, could be explained by the induction of activated protein C resistance. In a
      society that is less prepared to accept unwanted side effects from medications,
      it is recommended that increased attention be given to patient selection, and
      possibly the incorporation into this process of some of the more recently
      discovered hypercoagulability markers.

PMID- 10912637
TI  - Cancer, thrombosis, and anticoagulants.
AB  - Rapid progress has been made recently in our understanding of the pathogenesis of
      coagulation activation in malignancy and mechanisms by which the coagulation
      mechanism may control malignant growth. Idiopathic thromboembolic disease may be
      the sentinel presentation in patients subsequently diagnosed with malignancy.
      Thrombosis complicating the course of malignancy may be notoriously difficult to
      treat, but the introduction of the low-molecular-weight heparins has greatly
      improved management and may obviate the need for invasive approaches, such as the
      use of inferior vena cava filters, in many cases. Tantalizing clues from clinical
      trials of anticoagulant therapy in cancer have suggested that components of
      coagulation pathways may support tumor growth. Many of these can be intercepted
      using drugs that are well known and non-toxic. The importance of performing high
      quality controlled clinical trials that build on past studies and on data from
      basic research cannot be overemphasized.

PMID- 10912638
TI  - Diagnosis of deep-vein thrombosis in the year 2000.
AB  - Deep-vein thrombosis is a relatively common disease, amenable to therapy but with
      a potentially fatal outcome if untreated. The diagnosis can be made in most
      patients with the noninvasive imaging procedure ultrasonography, but limitations
      exist. As with all tests, there is a potential for false-positive and false
      negative results. The latter are especially an issue for calf vein thrombi, and
      this in part has led to the concept of serial testing of the proximal venous
      system and not imaging the calf. The premise of the repeat (serial) test is that
      only thrombi that extend to the proximal system are clinically relevant and such
      thrombi will be detected on the repeat test. However, despite the safety of the
      serial testing concept, it is inconvenient and expensive. In the last few years,
      the diagnostic process has been improved by the validation of a clinical model
      that accurately categorizes patients as having low, moderate, or high
      probability. Among the improvements this provides is the elimination of serial
      testing if the ultrasonogram is normal and the clinical probability low. The
      fibrin degradation product D-dimer has been demonstrated to have a high negative
      predictive value and has also proven useful in diagnostic algorithms. The
      combination of the D-dimer with clinical model assessment will enable diagnostic
      testing strategies that are more safe, effective, and convenient for patients.

PMID- 10912639
TI  - Recommendations for prophylaxis of venous thromboembolism: International
      Consensus and the American College of Chest Physicians Fifth Consensus Conference
      on antithrombotic therapy.
AB  - The primary purpose of a Consensus Conference is to provide informed guidance on
      treatment decisions, assisting clinicians to make the optimal therapeutic choice
      for the patient, and providing protection against unjustified malpractice
      actions. The First American College of Chest Physicians (ACCP) Consensus
      Conference took place in 1985 and, using a systematic approach, provided
      recommendations for antithrombotic therapy based on published studies, and graded
      those recommendations on the level of clinical evidence. The European Consensus
      Conference was convened in 1991 to build on this process. During this period, the
      main developments included the introduction and widespread use of new
      thromboprophylactic agents such as low-molecular-weight heparins, and improved
      risk assessment, including an awareness that out-patients and general medical
      patients may also be at risk. Subsequently, the recommendations have been
      carefully reviewed and updated by experts who represent the extensive range of
      opinions in the field. The latest International Consensus Statement was published
      in 1997, and the most recent ACCP Consensus in 1998 and they provide extensive
      practice guidelines in the management of venous thromboembolism.

PMID- 10912640
TI  - Duration of anticoagulants in acute or recurrent venous thromboembolism.
AB  - While the most recent trend in secondary prophylaxis after venous thromboembolism
      has been toward a prolonged duration, it has become obvious that
      individualization according to risk factors is crucial. Subgroup analyses in a
      long-term follow-up of a previous trial, as well as new trials on patients with
      idiopathic thromboembolism, have now improved our base of evidence. Many studies
      on the influence of biochemical factors in the risk of recurrence have also been
      published recently. This review should be helpful in-the individual decision on
      how to tailor the duration of anticoagulation.

PMID- 10912641
TI  - Long-term treatment of venous thromboembolism with low-molecular-weight heparin.
AB  - Vitamin K antagonists are the most widely used form of long-term treatment of
      patients with venous thromboembolism (VTE). In certain patients, however, the
      desire to initiate oral anticoagulant therapy is tempered by concern about the
      risk of bleeding. In these cases, consideration should be given to alternative
      forms of treatment. Unfractionated heparin (UFH) may be an alternative, but it
      requires twice-daily subcutaneous administration, and the dosage must be adjusted
      after periodic blood tests. Therapy with low-molecular-weight heparin (LMWH) is
      the likely practical solution to this dilemma. Up to now, four small randomized
      trials have compared the efficacy and safety of LMWH therapy as an alternative to
      oral anticoagulants. When the results of the four studies are combined, a
      significant decrease is found in the bleeding rate in patients receiving LMWH.
      Two further studies by our group confirm this lower bleeding rate in patients on
      LMWH therapy. According to these data, we suggest that LMWH could be an
      alternative to oral anticoagulants in patients who cannot attend the laboratory
      for prothrombin time monitoring, as well as those who are at high risk for
      bleeding.

PMID- 10912642
TI  - Recurrent venous thromboembolism: diagnosis and management.
AB  - A diagnosis of recurrent venous thromboembolism is commonly suspected by
      physicians in the clinical setting. Many do not realize that recurrent venous
      thromboembolism may mimic the first venous thromboembolic event (VTE) and that
      only 20 to 30% of patients who have had a first VTE actually have objective
      recurrent thrombotic disease. Objective testing is necessary to prevent the
      misdiagnosis of thrombophilia in patients and the associated exposure to
      prolonged anticoagulant treatment that accompanies that diagnosis. In patients
      with clinically suspected recurrent venous thrombosis, compression
      ultrasonography in a new venous segment is the preferred diagnostic approach and
      contrast venography is an alternative test. There is insufficient evidence to
      know whether D-dimer testing is an effective approach to the diagnosis of
      thrombophilia. In patients with suspected recurrent pulmonary embolism, the
      diagnostic method should begin with ventilation/perfusion lung-imaging and a
      complementary pulmonary angiography when the results of initial tests are
      equivocal. Patients with recurrent venous thromboembolism should be treated with
      anticoagulants for longer than 6 months but the precise period depends on the
      patient's risk of bleeding as a result of the treatment. Finally, there is
      currently a lack of evidence that risk for recurrent VTE is increased in patients
      with a first episode of venous thromboembolism and heterozygous factor V Leiden
      mutation or the G2021OA prothrombin mutation.

PMID- 10912643
TI  - The post-thrombotic syndrome.
AB  - One of every three patients with deep-vein thrombosis of the lower extremities
      will develop, within 5 years, post-thrombotic sequelae that vary from minor signs
      to severe manifestations such as chronic pain, intractable edema, and leg
      ulceration. The post-thrombotic syndrome (PTS) develops as a result of the
      combination of venous hypertension due to persistent outflow obstruction or
      valvular incompetence and abnormal microvasculature or lymphatic function. Among
      factors potentially related to the development of PTS, recurrent ipsilateral
      thrombosis plays a major role. Whether the extent and the location of the initial
      thrombosis are associated with the development of PTS is still controversial. The
      diagnosis of PTS can be accepted on clinical grounds for patients with a history
      of venous thrombosis. The combination of a standardized clinical evaluation with
      the results of compression ultrasonography and Doppler ultrasonography helps
      diagnose or exclude a previous proximal-vein thrombosis. Prevention of recurrent
      thrombosis and use of compression elastic stockings are the cornerstones of PTS
      prevention. The management of this condition is demanding and often frustrating.
      Although several surgical procedures have been tested, conservative treatment is
      largely preferable, as more than 50% of patients either remain stable or improve
      during long-term follow-up, if carefully supervised and instructed to wear proper
      elastic stockings. Clinical presentation helps predict the prognosis, being the
      outcome of patients who refer with initially severe manifestations more favorable
      than that of patients whose symptoms progressively deteriorate over time.

PMID- 10912645
TI  - Neoplasms of the lung.

PMID- 10912646
TI  - Approach to pulmonary metastases.
AB  - The prognosis and response to therapy of metastases to the lungs are variable and
      highly dependent on the origin of the primary tumor and on the extent and pattern
      of spread. Due to the complex pathogenesis underlying the development of
      pulmonary metastases, specific tumor types often display characteristic clinical
      and radiographic patterns. Understanding these concepts is of paramount
      importance when planning a diagnostic work-up for patients with possible
      pulmonary metastases. This review presents state of the art strategies in
      imaging, medical therapy, and surgery. It should provide the busy pulmonologist
      with the information needed to devise safe and efficient diagnostic and treatment
      strategies for patients with pulmonary metastases of extrathoracic origin.

PMID- 10912644
TI  - Venous thromboembolism in heparin-induced thrombocytopenia.
AB  - Deep-vein thrombosis (DVT) and pulmonary embolism are among the most common
      complications of heparin-induced thrombocytopenia (HIT), an antibody-mediated
      adverse effect of heparin that leads paradoxically to in vivo activation of
      platelets and the coagulation system. Inappropriate treatment of HIT-associated
      DVT with warfarin can cause the DVT to progress to limb gangrene: this results
      from impaired ability of the protein C natural anticoagulant pathway to down
      regulate thrombin generation, thus leading to microvascular thrombosis and tissue
      necrosis. Appreciation of the importance of coagulation system activation in HIT
      provides a rationale for treatments that reduce thrombin generation, either via
      inhibiting factor Xa (danaparoid) or via inhibiting thrombin directly
      (lepirudin). Clinicians should know how to distinguish HIT from other
      thrombocytopenic disorders: for example, thrombocytopenia associated with
      pulmonary embolism can mimic HIT (pseudo-HIT), and acute dyspnea that can mimic
      acute pulmonary embolism can result from acute in vivo platelet activation in a
      patient with HIT antibodies who receives heparin bolus therapy (pseudo-pulmonary
      embolism).

PMID- 10912647
TI  - Solitary pulmonary nodule: time to think small.
AB  - The challenge presented by a solitary pulmonary nodule has faced physicians and
      patients since the advent of the chest radiograph. Is the nodule malignant or
      benign? When should something be done about it and what should that be? The
      majority of solitary nodules are benign, but the detection of a nodule may be the
      first and only chance for cure in the patient with lung cancer. The expanding
      availability and use of computed tomography are leading to increased numbers and
      decreased size of nodules detected. Surgical resection remains the most sensitive
      and specific method of analysis but introduces morbidity and mortality that may
      be unnecessary and avoidable. Advances in radiographic techniques have improved
      the ability to noninvasively identify whether a nodule is likely malignant or
      benign. Application of these techniques may ease the decision making and reduce
      the incision making.

PMID- 10912648
TI  - Environmental asbestos exposure and mesothelioma.
AB  - Epidemiologic studies of mesothelioma have focused primarily on occupational
      exposures to asbestos. Nonoccupational exposure to asbestos can be grouped into
      three main categories: paraoccupational (familial), neighborhood, and true
      environmental exposures. Elevated mesothelioma rates not attributable to
      occupational exposures have been observed in asbestos mining and manufacturing
      areas. Asbestos is one of the most dangerous environmental carcinogens because of
      the small dose known to cause mesothelioma and the rapid lethality of the disease
      once it develops. Further research is needed to characterize the contribution and
      risk profile for environmental asbestos and mesothelioma, and for the development
      of public health policy.

PMID- 10912649
TI  - Bronchoscopic photodynamic diagnosis and therapy for lung cancer.
AB  - Photodynamic diagnosis and therapy have exciting potential in lung cancer
      management. Fluorescence bronchoscopy enhances the detection of preinvasive
      lesions and early invasive carcinomas involving the central airways, whereas
      photodynamic therapy (PDT) provides an effective method for treating these
      lesions with preservation of lung tissue. However, the natural history of
      preinvasive lesions is poorly understood and so the value of treatment remains
      unclear. Although treatment for early invasive carcinomas'is not open to
      question, the possibility of undetected nodal disease means that PDT is unlikely
      to replace surgical resection in patients who are fit for thoracotomy. PDT also
      provides an effective method of palliating patients with advanced obstructing
      endobronchial tumors. Although it is considered superior to simple tumor
      debulking, its usefulness is limited by transient but potentially severe skin
      photosensitivity. There is therefore a need to develop new photosensitizing drugs
      with less severe side effects.

PMID- 10912650
TI  - Management of small cell cancer of the lung.
AB  - Small cell lung cancer (SCLC) accounts for 20% to 25% of bronchogenic carcinoma
      cases. Combination chemotherapy offers the best chance for improved survival.
      Cisplatin plus etoposide appears to be the most reasonable choice for first line
      therapy. Increasing dose intensity, although sometimes associated with higher
      response rates, does not appear to significantly improve survival. Concurrent
      thoracic radiotherapy administered early in the course of chemotherapy confers a
      survival advantage over chemotherapy alone in limited-stage SCLC. Prophylactic
      cranial irradiation reduces central nervous system recurrences with minimal long
      term sequelae and appears to improve survival. Several new cytotoxic agents are
      active in SCLC. These include gemcitabine, paclitaxel, docetaxel, topotecan,
      irinotecan, and JM216. Novel approaches being investigated include antibodies to
      factors expressed by SCLC cells and agents targeting angiogenesis, cell cycle
      regulation, and cell-signaling pathways.

PMID- 10912652
TI  - Bibliography. Current world literature. Diseases of the pleura.

PMID- 10912653
TI  - Bibliography. Current world literature. Disorders of pulmonary circulation.

PMID- 10912651
TI  - Primary non-small-cell lung cancer: determining the suitability of the patient
      and tumor for resection.
AB  - Choosing resective surgery for patients with bronchogenic carcinoma requires
      assessments of tumor suitability and patient suitability. Tumor suitability is
      largely dependent on the assessed stage of the tumor complex, based on
      characteristics of the primary tumor, detection of lymph node metastases, and
      detection of distant metastases. Imaging tests that assist in the determination
      of tumor stage include computed tomographic scans and positron emission
      tomographic (PET) scans. PET scans are more sensitive and specific than computed
      tomography. PET is also helpful in screening for distant metastases.
      Mediastinoscopy is required in most cases of mediastinal adenopathy. Patient
      suitability is assessed by predicting short-term surgical mortality, and the
      likelihood of crippling long-term respiratory failure. There is no single test
      that provides such information. Pulmonary function tests can be used to calculate
      the "predicted postoperative" function, and several algorithmic approaches have
      been devised to predict surgical risk. Assessments of regional pulmonary function
      are obtained with quantitative perfusion scintiscans. Cardiac function is also an
      important factor.

PMID- 10912654
TI  - Bibliography. Current world literature. Neoplasms of the lung.

PMID- 10912655
TI  - The physiology of the transplanted small bowel: an overview with insight into
      graft function.

PMID- 10912656
TI  - Distribution of atrophy in Helicobacter pylori-infected subjects taking proton
      pump inhibitors.
AB  - BACKGROUND: Gastric atrophy is associated with Helicobacter pylori infection.
      Conflicting results have been obtained as to whether acid suppressant therapy
      hastens the development or changes the distribution of atrophy in the stomach.
      The aim of this study was to investigate whether concomitant proton pump
      inhibitor (PPI) therapy in H. pylori-infected individuals resulted in an increase
      or an alteration in atrophy distribution and whether this was reflected by the
      plasma gastrin. METHODS: Multiple gastric biopsy specimens were taken from the
      antrum and corpus from 46 H. pylori-infected subjects, 18 of whom were taking
      PPIs, and assessed histologically by the updated Sydney System. The control group
      was age- and sex-matched to the index group. Fasting gastrin levels were
      measured. RESULTS: In the control group there was no significant tendency for
      either antral or corpus atrophy to predominate (P = 0.44). In the treatment group
      there was a significant tendency for corpus as opposed to antral atrophy to
      develop (P < 0.001). There was no significant difference in the overall atrophy
      score between the treated and untreated groups (P = 0.76). Fasting gastrin levels
      were significantly higher in the treated group (P < 0.001). CONCLUSIONS:
      Treatment with PPIs in H. pylori-infected subjects does not lead to an overall
      increase in gastric atrophy. It does, however, result in an increased prevalence
      of corpus as opposed to antral atrophy. This is associated with a significantly
      higher gastrin level.

PMID- 10912657
TI  - Perceptual hyperreactivity to auditory stimuli in patients with irritable bowel
      syndrome.
AB  - BACKGROUND: Patients with irritable bowel syndrome (IBS) have abnormal perception
      of visceral stimuli; however, no study has so far investigated the perception of
      non-visceral stimuli in IBS. In the present study we used event-related
      potentials (ERP) to study whether IBS patients differed from healthy controls in
      processing of auditory stimuli and, if so, how this was influenced by emotions.
      METHODS: We compared ERPs to auditory stimuli in 40 female diarrhoea-predominant
      IBS patients without current psychiatric illness with those in 20 healthy
      controls. Tones were used as standard and target stimuli, and words with
      emotional content as distractors. Characteristics of the first negative wave
      (N100) and mean amplitudes in 50-msec time intervals between 150 and 600 msec
      were assessed. RESULTS: At the frontal midline electrode IBS patients had
      significantly enhanced N100 amplitude to all stimuli, persisting after adjustment
      for age, current emotions, and personality traits. They additionally had enhanced
      waves 200-300 msec and 400-500 msec after stimulus. The latter differences
      disappeared after adjustment for emotions and personality traits. CONCLUSIONS: In
      the frontal brain region, IBS patients seem to have a hyperreactivity to auditory
      stimuli compared with controls. Later elements (P300, N400) of stimulus
      processing were influenced by emotions and personality traits. These may possibly
      contribute to changes in intestinal motility caused by stress. The study
      indicates that aberrant brain functioning may be an element of the irritable
      bowel syndrome. It may elucidate a mechanism for brain-gut interaction by which
      psychosocial stress may influence visceral pain perception in non-psychiatric
      subjects with an intestinal motility disorder and also the efficacy of
      psychiatric treatment on IBS symptoms.

PMID- 10912658
TI  - Scintigraphic assessment of interdigestive duodenogastric reflux in humans:
      distinguishing between duodenal and biliary reflux material.
AB  - BACKGROUND: Late duodenal phase III is characterized by retroperistalsis. The
      physiologic function of this phenomenon is unknown. Our aim was to study the
      relationship between duodenal motility and the transport of duodenal contents
      from the biliary tract and the duodenum by using a double-isotope technique.
      METHODS: Manometric analysis of the direction of interdigestive duodenal pressure
      waves was performed in 12 volunteers. Duodenal marker was infused directly into
      the proximal duodenum, and bile marker was infused intravenously for 2 h.
      Radionuclide activity was examined for regions corresponding to the stomach,
      gallbladder, and duodenum. RESULTS: In phase II, antegrade pressure waves
      dominated with propulsion of both markers to the jejunum. Retroperistalsis
      occurred in 90% of the activity fronts and was always (100%) followed by
      retropulsion of duodenal marker to the stomach. A clear-cut reflux of bile marker
      was seen in only 17% of the activity fronts. The incidence rate of duodenogastric
      reflux was highest in phase III (P=0.008) compared with phase II with an
      infrequent (P=0.002) admixture of bile. Bile marker contents increased abruptly
      in the gallbladder during phase III. CONCLUSIONS: Late phase III acts as a
      retroperistaltic pump, retropelling duodenal contents to the stomach. In this
      physiologic duodenogastric reflux. bile is avoided by deviation to the
      gallbladder, probably by a phase lll-associated occlusion of the sphincter Oddi.

PMID- 10912659
TI  - The prevalence and severity of intestinal disaccharidase deficiency in human
      immunodeficiency virus-infected subjects.
AB  - BACKGROUND: Gastrointestinal symptoms are distressing features of human
      immunodeficiency virus (HIV) infection, and management is often empirical,
      including withdrawal of dietary lactose. We assessed the prevalence and severity
      of intestinal disaccharidase deficiency in vitro and in vivo. METHODS: Fifty-four
      HIV-seropositive patients (19 HIV well +/- mild diarrhoea, 7 acquired
      immunodeficiency syndrome (AIDS) well, and 28 AIDS with diarrhoea) were studied
      with a combined non-invasive absorption-permeability-disaccharidase test that
      enables quantitative assessment of the rate of intestinal hydrolysis of lactose,
      sucrose, and palatinose. Thirty patients had jejunal biopsy specimens suitable
      for histomorphometric assessment, and 36 had in vitro disaccharidase activity
      measurement. RESULTS: Patients with HIV (with mild diarrhoea) and AIDS (with and
      without severe diarrhoea) had frequent but mild histomorphometric changes in
      jejunal specimens. This was associated with frequent (21%-100%) and often severe
      in vitro jejunal disaccharidase deficiency. In vivo hydrolysis of lactose,
      sucrose, and palatinose was impaired in 25%-75% of patients, apart from HIV well
      patients, who were normal. The prevalence of the in vivo lactase and sucrase
      deficiency was significantly (P < 0.006) lower than in vitro and severe in about
      30%. CONCLUSIONS: Intestinal disaccharidase deficiency is common both in vitro
      and in vivo in HIV-seropositive patients but sufficiently severe to consider
      lactose withdrawal only in about a quarter of the patients with AIDS and
      diarrhoea.

PMID- 10912660
TI  - Variations in colonic H2 and CO2 production as a cause of inadequate diagnosis of
      carbohydrate maldigestion in breath tests.
AB  - BACKGROUND: Lactose maldigestion is usually diagnosed by means of the H2 breath
      test. When 13C-lactose is used as substrate, a 13CO2 breath test can be performed
      simultaneously. In an earlier publication we described the relation between both
      the H2 and 13CO2 exhalation in breath and the measured intestinal lactase
      activity after consumption of 13C-lactose. We found a discrepancy between both
      breath test results in 36% of the cases. To investigate the possible cause of
      these incongruous breath test results, we studied gas production from
      carbohydrate in the colon, using 13C-lactulose as a non-absorbable substrate.
      METHODS: Experiments were performed in 21 subjects, by applying 5 different doses
      of 13C-lactulose. Repeatability studies were performed in six of these subjects,
      using 10 g substrate (three tests with 1-week intervals). RESULTS: Both the H2
      and the 13CO2 excretion in breath varied strongly interindividually and
      intraindividually after consumption of 13C-lactulose. In both cases no dose
      response relation was observed. A significant positive linear relationship was
      found between H2 and 13CO exhalation (r = 0.45, P < 0.005). Extrapolation of
      these results to 13C-lactose breath tests indicates that the colonic contribution
      of 13CO2 production to the total 13CO2 excretion in breath varies but is on the
      average large enough to cause false-negative 13CO2 breath test results.
      CONCLUSIONS: Excretion in breath of 13CO2 produced in the colon during a 13C
      lactulose breath test correlates with the breath H2 excretion. This could explain
      the occurrence of false-negative 13CO2 lactose breath tests when colonic gas
      production is high and false-negative lactose H2 breath test results when gas
      production is low. It can also explain the improved sensitivity of the combined
      H2/13CO2 lactose breath test compared with both breath tests alone.

PMID- 10912661
TI  - Continuous infusion of cholecystokinin leads to down-regulation of the
      cholecystokinin-A receptor in the rat pancreas.
AB  - BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently
      increased the proliferation of pancreatic acinar cells, whereas the CCK-A
      receptor antagonist devazepide decreased such proliferation. This effect ceased
      after 3 days. CCK-8S or devazepide injected twice daily induced a persistent
      effect on the cell proliferation involving the major cells of the exocrine
      pancreas. The aim of this study was to examine the effect of continuous infusion
      of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague
      Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S,
      200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic
      minipumps. The rats were killed after 4 days; I h before being killed they
      received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected
      for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence
      for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A
      receptor mRNA was performed for examination and semiquantification of receptor
      gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase
      in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect
      the CCK level but decreased the pancreatic weight by 24% compared with BSA
      infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell
      proliferation. Immunofluorescence for the CCK-A receptor showed a decreased
      labeling intensity after CCK-8S infusion. The mean optical density of in situ
      hybridization labeling of the sections from CCK-8S-treated rats was decreased to
      37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene
      expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a
      downregulation of the receptor gene expression in pancreatic acinar cells and
      decreased labeling of the receptor at immunohistochemistry. The results suggest
      that down-regulation of the receptor is a protective mechanism against
      overstimulation.

PMID- 10912662
TI  - Inflammatory bowel disease promotes venous thrombosis earlier in life.
AB  - BACKGROUND: Patients with inflammatory bowel disease (IBD) may be at increased
      risk of having venous thromboembolism. METHODS: Medical records from 1,253 IBD
      patients attending hospital care during the years 1987-97 were studied. These
      patients were recruited from a population of 340,000 inhabitants. Patients with
      verified venous thrombosis were characterized clinically, and blood samples were
      examined for coagulopathy including analyses of antithrombin, plasminogen,
      protein C, protein S, factor V, and prothrombin mutations. As control groups we
      used 99 patients with verified venous thrombosis and no history of IBD and 288
      volunteers with no history of thrombosis. RESULTS: The incidence of venous
      thrombosis was 1.5/1,000 IBD patients per year, which is comparable to the
      background population. The mean age was significantly lower in IBD patients than
      in non-IBD patients (53 versus 64 years, P= 0.0225). We found one patient with
      antithrombin deficiency but none with protein C, protein S, or plasminogen
      deficiency. Factor V mutation was as prevalent in IBD patients with thrombosis as
      in thrombotic non-IBD patients (27% versus 28%) and 3.0 times (95% confidence
      interval, 0.8-11.9) more frequent in IBD patients with thrombosis than in healthy
      controls. Prothrombin mutation was not detected in IBD patients with venous
      thrombosis. CONCLUSION: We found no increased incidence of venous thrombosis in
      IBD patients compared with a background population. However, IBD patients had
      venous thrombosis earlier in life than non-IBD patients. Although factor V
      mutation may contribute to thrombosis, IBD acts as a trigger through mechanisms
      that still remain unexplained.

PMID- 10912663
TI  - Allergy and mucosal eosinophil infiltrate in ulcerative colitis.
AB  - BACKGROUND: Data on allergy in ulcerative colitis (UC) have led to conflicting
      conclusions without proving any causal association. In this report we have
      investigated the presence of allergy and its possible relation with chronic
      colonic inflammation in patients with UC. METHODS: Fifty UC patients underwent
      clinical, endoscopic, and histologic evaluations. The allergologic study included
      family/personal history; prick/patch exposition to airborne, food, and contact
      allergens; total serum IgE; and quantification of eosinophils in peripheral blood
      and intestinal mucosa. Diagnosis of rhinitis, conjunctivitis, and asthma was
      confirmed by specific provocation tests. Fifty healthy subjects were studied as
      control group. RESULTS: A higher prevalence of allergic symptoms was found in
      patients (56%) and their first-degree relatives (52%) than in controls (18% and
      26%) (P < 0.0001; P = 0.008). In patients skin tests showed increased rates of
      immediate (54%) and delayed-type (20%) hypersensitivity compared with controls
      (30% and 6%) (P= 0.01; P= 0.03). Diagnosis of allergic IgE-mediated disease was
      made in 19 cases and 6 controls (P= 0.01), and allergic contact dermatitis in 10
      and 3, respectively (P= 0.03). IgE levels were higher in UC patients than in
      controls (P=0.02). No dose-response relationship was found between degree of
      colonic tissue eosinophilia and clinical. endoscopic, and histologic disease
      severity. The degree of colonic tissue eosinophilia was higher in the presence of
      skin reactivity to food allergens. CONCLUSIONS: UC patients frequently show
      several markers of allergy. In particular, our data suggest an association
      between ulcerative colitis, tissue eosinophilia, and type-I allergy.

PMID- 10912664
TI  - Chagasic megacolon and proximal jejunum microbiota.
AB  - BACKGROUND: Among other factors, control of jejunal microflora depends on
      intestinal emptiness, and it can be impaired by Chagas disease. This study was
      developed to identify the microecology of the proximal jejunum in chagasic
      megacolon. Our objective was to characterize both the jejunal microbial stasis
      before surgery and the microflora after surgical treatment in patients with
      chagasic megacolon. METHODS: The intestinal fluids were collected, and the
      proximal jejunum microflora was analyzed. RESULTS: Preoperative microflora had
      shown an increase in bacteria compatible with bacterial overgrowth syndrome,
      mainly facultative and strict anaerobes microorganisms and fungi. The microflora
      had changed in the postoperative period in 83% of these patients, with
      significant decrease in the number of transient microorganisms. CONCLUSIONS:
      Chagasic megacolon was related to an increase in jejunal microflora. By removing
      the impairment of the colon there was a transient decrease in the proximal
      jejunum microflora.

PMID- 10912665
TI  - Clinicopathologic features and FHIT gene expression in sporadic colorectal
      adenocarcinomas.
AB  - BACKGROUND: The putative tumour suppressor gene FHIT (fragile histidine triad)
      spans the common fragile site FRA3B, which is highly susceptible to breaks and
      deletions induced by genotoxic agents. Tumours associated with exposure to
      carcinogens, such as colorectal adenocarcinomas, should be particularly
      susceptible to alterations in the FHIT gene. We studied the frequency of FHIT
      alterations and their correlations with clinicopathologic features in sporadic
      colon carcinomas. METHODS: FHIT expression was investigated by reverse
      transcription polymerase chain reaction in 56 primary sporadic colorectal
      carcinomas. The same tumours and matched normal tissues were also investigated
      for loss of heterozygosity by using two markers located inside the FHIT gene.
      RESULTS: Twenty-nine of 56 tumours (51.8%) expressed aberrant FHIT transcripts.
      Four tumours had absence or nearly undetectable levels of the normal-sized FHIT
      transcript. Sequencing analysis of the altered transcripts showed FHIT mRNA
      lacking one or more exons, more frequent deletions of exons 4-5-6 or 4-5-6-7-8.
      At the genomic level 46.4% (13 of 28) of the cases showed alterations involving
      FHIT locus. We did not find any correlation between FHIT gene alterations and
      clinicopathologic characteristics of the tumours. CONCLUSIONS: Since the FHIT
      gene is frequently altered, its role in the molecular pathogenesis of sporadic
      colon carcinoma deserves further investigation.

PMID- 10912666
TI  - Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon
      plus placebo in patients with chronic hepatitis C resistant to interferon.
AB  - BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon
      (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the
      efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients
      were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44)
      plus interferon (3 MU three times weekly) for 6 months and were then followed up
      for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70%
      had HCV genotype 1. Five and four patients withdrew from the combination and the
      monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and
      gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001)
      in the combination group than in the monotherapy group; the differences were no
      longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8
      patients in the combination and the monotherapy groups, respectively (P = 0.67).
      In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year
      four versus one patient had a sustained normalization of ALAT, and in one patient
      the HCV RNA became negative. There was no difference in the histologic
      progression. In this setting, in contrast to chronic cholestasis, UDCA
      administration induced an increase in total serum bile acids and did not change
      primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective
      than IFN alone in terms of ALAT but not in terms of the virologic response. These
      results favor the hypothesis that UDCA has an effect on the biochemical indices
      of cellular injury independent of a change in primary bile acids.

PMID- 10912668
TI  - Transjugular intrahepatic portosystemic shunt for cirrhosis and ascites: Effects
      in patients with organic or functional renal failure.
AB  - BACKGROUND: A transjugular intrahepatic portosystemic shunt (TIPS) is
      increasingly being used for treatment of patients with refractory ascites and
      functional renal failure. In contrast, organic renal disease is commonly
      considered a relative contraindication for TIPS placement. The aim of this pilot
      study was to investigate the effects of TIPS in patients with refractory ascites
      and organic or functional renal impairment. METHODS: A TIPS was placed for
      refractory or intractable ascites in 10 consecutive patients with liver cirrhosis
      and impaired renal function (serum creatinine > 1.5 mg/100 ml). Four of them had
      organic kidney disorders. Of these patients, three had moderate renal impairment,
      and one had end-stage renal disease and needed hemodialysis every other day. The
      other six patients had functional renal impairment due to the underlying liver
      disease. RESULTS: TIPS was effective in reducing ascites in 8 of 10 patients,
      including all patients with organic renal disease. Furthermore, after TIPS the
      renal function improved in all patients. Serum creatinine and serum urea levels
      decreased significantly from 1.8 +/- 0.1 to 1.5 +/- 0.1 mg/100 ml (P < 0.05) and
      from 107 +/- 13 to 78 +/- 14 mg/100 ml (P < 0.05), respectively. The renal
      function of the three patients with organic renal failure improved similarly, as
      observed in the six patients with functional renal failure. In the patient on
      hemodialysis, TIPS was effective in reducing the frequency of paracenteses.
      CONCLUSION: TIPS may be useful in patients with functional and in patients with
      organic renal disease, resulting in improvement of ascites and renal function.

PMID- 10912667
TI  - Non-Invasive assessment of human hepatic mitochondrial function through the 13C
      methionine breath test.
AB  - BACKGROUND: Mitochondrial metabolism is essential for liver function, and the
      availability of simple and non-invasive tests able to assess hepatic
      mitochondrial function could be extremely useful. Since the amino acid methionine
      is mostly oxidized by liver mitochondria, we investigated the feasibility of a
      breath test with 13C-methionine in healthy subjects to assess hepatic
      mitochondrial function before and after ethanol-induced oxidative stress.
      METHODS: Twenty healthy male volunteers received 2 mg/kg body weight [methyl-13C]
      methionine. Breath 13CO2 enrichment was measured at base line and every 15 min
      thereafter for 180 min. Forty-eight hours later the test was repeated 30 min
      after the ingestion of ethanol (0.3 g/kg body weight). RESULTS: After oral
      administration of methionine, 13CO2 excretion reached a peak (4.76% +/- 0.9%)
      within 30-60 min and then decreased progressively. The cumulative 13CO2 excretion
      within 3 h was 7.81% +/- 0.66%. After ethanol-induced oxidative stress, 13CO2
      excretion increased slowly, with a delayed and significantly decreased peak
      (2.13% +/- 0.45%; P < 0.05). The cumulative 13CO2 exhalation was significantly
      decreased already at 60 min (1.22% +/- 0.29%; P < 0.05). CONCLUSIONS: The present
      results seem to indicate that the 13C-methionine breath test could act as a
      marker to estimate the oxidative capacity of liver mitochondria in healthy
      subjects. Further study, however, is still needed to confirm the validity of the
      test, which could yield clinically useful information in various liver pathologic
      conditions.

PMID- 10912669
TI  - Utilization of short-chain fatty acids by colonic mucosal tissue strips. A new
      method of assessing colonic mucosal metabolism.
AB  - BACKGROUND: Previous metabolic studies of the colonic mucosa have been done using
      isolated cells or small biopsy specimens. METHODS: A new method for assessing the
      utilization of short-chain fatty acids in human colonic mucosal tissue strips
      considerably larger than routine samples was evaluated and compared with the
      method of isolated colonocytes. Human colonic mucosal strips and isolated human
      and rat colonocytes were incubated with acetate (C2), butyrate (C4), and
      hexanoate (C6), and oxidation rates obtained by quantifying the production of
      CO2. RESULTS: The wet weight of strips was highly correlated with the production
      of CO2, and intersample coefficient of variance was <10%. The production of CO2
      from the oxidation of C2, C4, and C6 was in the order of C2 > C4 > C6 for both
      strips and isolated human and rat colonocytes. The production of adenosine
      triphosphate (ATP) in strips and isolated human and rat colonocytes was in the
      order of C2 < or = C4 < or = C6. The Km value for the oxidation of butyrate to
      CO2 in strips (1.8 mmol/l) was several times higher than previously reported for
      isolated human and rat colonocytes (0.1-0.3 mmol/l). CONCLUSIONS: This new method
      is highly reproducible and able to assess the metabolic activity of the colonic
      mucosa. The high Km value of butyrate oxidation in mucosal strips seems to
      reflect the in vivo Km value of colonocytes and shows the importance of a
      preserved anatomic structure in metabolic studies of the colonic epithelium. The
      low Km value for isolated colonocytes probably reflects the intracellular ability
      to oxidize butyrate. We propose that both isolated colonocytes and mucosal strips
      be used in studies of colonic mucosal metabolism. This method is relevant in
      disease states of the colon in which a disagreement prevails as to the ability to
      oxidize butyrate by colonocytes, such as in ulcerative colitis.

PMID- 10912670
TI  - Graft-versus-Host disease-like syndrome in malignant thymoma.
AB  - Allogenic transfusion of immunocompetent T lymphocytes into an immunodeficient
      recipient is necessary for the development of graft-versus-host-disease (GVHD).
      The gastrointestinal tract is one of the most involved organs in human GVHD, and
      single-cell necrosis with apoptotic change and crypt abscess are characteristic
      histopathologic features. The thymus is important in immune regulation, and
      dysregulation of the immune system can be expected once its microenvironment is
      disrupted. We report the case of a 38-year-old woman with malignant thymoma
      without transplantation or transfusion history who initially presented with
      myasthenia gravis and clinically developed a GVHD-like syndrome with
      characteristic GVHD-like colitis on colonoscopy. We propose that disruption of
      the thymic microenvironment caused a dysregulated immune system and development
      of a GVHD-like syndrome.

PMID- 10912671
TI  - Circulating Levels of Matrix Metalloproteinase-9 in Patients with Colorectal
      Cancer.

PMID- 10912672
TI  - Complete nucleotide sequence of Japanese flounder (Paralichthys olivaceus)
      mitochondrial genome: structural properties and cue for resolving teleostean
      relationships.
AB  - We cloned and sequenced the complete mitochondrial genome of Japanese flounder
      (Paralichthys olivaceus). A circular 17,090 bp mitochondrial genome from the
      flounder contains 37 structural genes as in other vertebrates so far reported.
      This is the first report of the complete mitochondrial sequence from a higher
      teleostean fish (Acanthopterygii). The organization including gene order is quite
      similar to that of other teleostean fishes as well as placental mammals. The
      putative control region of the Japanese flounder mitochondrial genome contains a
      length variable region of about a 74 bp tandem repeat cluster. As a preliminary
      study we adopted the maximum likelihood and neighbor-joining inference methods to
      examine phylogenetic relationships among teleostean and related fishes.
      Comparisons of amino acid sequences of protein-coding genes and nucleotide
      sequences of tRNA genes resolved some middle to deep branches among some
      teleostean fishes. The flounder mitochondrial genome does not show an indication
      of evolutionary rate difference among teleosts leading to difficulty in
      phylogenetic analyses, and our data is useful for future evolutionary studies
      dealing with higher teleostean fishes.

PMID- 10912673
TI  - Major histocompatibility complex class I loci from the gray whale (Eschrichtius
      robustus).
AB  - Sequences from exons encoding the peptide binding region of MHC class I (MHC-I)
      molecules were isolated from California gray whale (Eschrichtius robustus)
      genomic DNA to initiate an investigation of variation in these genes in a
      cetacean. These represent the first mysticete MHC-I sequences to be reported. The
      analysis of gray whale MHC-I sequences suggests the presence of at least three
      loci, which share greatest similarity to MHC-I in the ungulates, consistent with
      current views on cetacean phylogenetics. The peptide binding region of MHC is the
      most polymorphic part of the molecule and analysis of the variation and
      synonymous to nonsynonymous substitution ratios in gray whale sequences found
      these genes to display polymorphism characteristics similar to that attributed to
      selection in other species.

PMID- 10912674
TI  - Recent radiation of Iberian barbel fish (Teleostei, Cyprinidae) inferred from
      cytochrome b genes.
AB  - Nucleotide sequence fragments of the mitochondrial DNA gene encoding cytochrome b
      were examined in 26 individuals belonging to the seven species of Barbus endemic
      to the Iberian Peninsula: Barbus haasi, B. bocagei, B. graellsii, B. sclateri, B.
      comiza, B. guiraonis, and B. microcephalus. Six of the seven currently recognized
      species can be distinguished on the basis of their cytochrome b nucleotide
      sequences. Sequence divergence estimates for Spanish species of Barbus (0-6.5%)
      are, in general, low in comparison to those reported for other fish species, and
      hybrid individuals were found. All of these observations suggest a recent
      radiation. The inferred phylogenetic tree has two main clades, one including B.
      graellsii, B. guiraonis, and B. microcephalus, and the other the remaining
      species groups.

PMID- 10912675
TI  - Anthocyanin inheritance and instability in purple basil (Ocimum basilicum L.).
AB  - The instability of the purple pigments (anthocyanins) in purple basil varieties
      (Ocimum basilicum L.) limits their use as ornamental plants and as a potential
      anthocyanin source. Several self-pollinated generations of all purple plants were
      unsuccessful in stabilizing anthocyanin expression. In this study we investigated
      the inheritance and stability patterns of leaf traits using the Purple Ruffles
      variety. The results from the complete diallele crosses indicated anthocyanin
      expression in vegetative tissue is controlled by two dominant genes and ruffled
      leaf texture is controlled by a single recessive gene. Genes controlling leaf
      margin and leaf base structures were tightly linked to leaf texture. Essential
      oil production and oil constituents in leaves did not change as a result of the
      reversion in color. Color stability in cuttings was affected by the environment
      and the location where cuttings were taken. An accumulation of secondary
      metabolites (apigenin, genistein, and kaempferol) in green-reverted sectors on
      purple leaves was detected using reverse-phase high-performance liquid
      chromatography (HPLC) analysis; this suggested a potential block in the
      anthocyanin pathway. We hypothesize the reversion mutation is occurring in an
      anthocyanin regulatory gene.

PMID- 10912676
TI  - Genetic analyses of two independent chlorophyll-deficient mutants identified
      among the progeny of a single chimeric foliage soybean plant.
AB  - Chimeric (variegated) foliage plants are frequently observed in many species. In
      soybean [Glycine max(L.) Merr.], progeny of chimeric plants are a source of
      nuclear and cytoplasmically inherited mutants. Self-pollinated progeny of a
      single chimeric plant derived from tissue culture of PI 427099 (Jilin 3) included
      plants with green foliage, chimeric foliage, yellow foliage (viable), and yellow
      foliage (lethal). Our objectives were to determine (1) inheritance, linkage, and
      allelism of the lethal-yellow mutant with known chlorophyll-deficient mutants;
      (2) inheritance, linkage, and allelism of the viable-yellow mutant with known
      chlorophyll-deficient mutants; (3) allelism of the lethal-yellow mutant with the
      viable-yellow mutant; and (4) male and female gamete transmission of the viable
      yellow mutant trait. The viable-yellow mutant was allelic to T323, y20 y20 (Ames
      2) Mdh1-n Mdh1-n (Ames 2) and was assigned genetic type collection number T361
      and gene symbol y20 y20 (Ames 24) Mdh1-n Mdh1-n (Ames 22). The lethal-yellow
      mutant was allelic to T225H (Y18 y18) and was assigned genetic type collection
      number T362H and gene symbol Y18 y18 (Ames 2). T225H became Y18 y18 (Ames 1). The
      two chlorophyll-deficient mutants were not linked to each other. There was no
      significant difference in F(1) male or female gamete transmission of the viable
      yellow mutant. However, many cross-combinations gave significant deviations from
      the expected 3 green plants:1 viable-yellow plant in the F(2) generation. The
      allelism of these two chlorophyll-deficient mutants with mutants T225H and T323,
      derived from putative transposable element systems, is intriguing. An explanation
      of this phenomenon awaits molecular experimentation.

PMID- 10912677
TI  - Epistatic interaction between vernalization genes Vrn-Am1 and Vrn-Am2 in diploid
      wheat.
AB  - Genes Vrn-A(m)1 and Vrn-A(m)2 control the vernalization requirement in diploid
      wheat (Triticum monococcum). The epistatic interaction between these two genes on
      flowering date was studied here using a factorial analysis of variance. One
      hundred and two F2 plants were classified according to their genotypes for
      molecular markers tightly linked to Vrn-A(m)1 and Vrn-A(m)2. Mean comparisons
      showed that the VrnA(m)2 allele for winter growth habit was dominant to the vrn
      A(m)2 allele for spring growth habit and that the Vrn-A(m)1 allele for spring
      growth habit was dominant to the vrn-A(m)1 allele for winter growth habit. A
      significant interaction was found between these two genes, suggesting that they
      work in the same developmental pathway. Plants homozygous for the recessive vrn
      A(m)2 allele for spring growth habit flowered earlier than plants from the Vrn
      A(m)2 class independently of the alleles present at Vrn-A(m)1. However,
      differences in heading date between plants with the Vrn-A(m)1 allele and those
      with the vrn-A(m)1 allele were significant only when the dominant Vrn-A(m)2
      allele was present. A genetic model for the action of these two vernalization
      genes is proposed in which the role of Vrn-A(m)1 is to counteract the Vrn-A(m)2
      mediated delay of flowering.

PMID- 10912678
TI  - Founder effects and the genetic structure of Coulter pine.
AB  - Mean expected heterozygosity at 33 isozyme loci decreased with latitude from
      0.193 near the southern extreme of Coulter pine's range to 0.107 at its northern
      extreme. This decrease was paralleled by a loss of alleles north of the
      Peninsular Ranges of southern California. Fifteen alleles dropped out along the
      roughly lineal range, at points coincident with large gaps in the species'
      distribution. The pattern may reflect a cascading series of founder events as
      Coulter pine invaded the Trans. verse Ranges and the South Coast Ranges from
      Pleistocene refugia. Alleles were not replaced following colonization, probably
      because migration, Nm, among populations is only 0.74-1.27, depending on
      estimator, the lowest values reported in any pines. Wright's (F(ST)) indicated
      that 16.5% of the total genic diversity is among populations. The fixation index,
      (F(IS)) of 0.072 indicated only a moderate excess of homozygotes. However, the
      northernmost outlier had significant excess homozygosity (F = 0.253).
      Hybridization may also play a role in the genetic structure of Coulter pine: 16
      alleles were novel, or private, occurring only where Coulter pine was sympatric
      with Jeffrey pine, particularly at San Benito Mountain. Some of these novel
      alleles could be the result of introgression from Jeffrey pine, or possibly
      represent hybrizymes, products of intragenic recombination between genomes.

PMID- 10912679
TI  - Investigating the genetic model for brown stem rot resistance in soybean.
AB  - Genetic analyses have indicated that brown stem rot (BSR) resistance in soybean
      is conferred by dominant alleles at three independent loci, the actions of which
      may be modified by linked or independent loci. A study was conducted to
      characterize the inheritance of BSR resistance in PI 567609, a soybean plant
      introduction from China. Segregating progeny from crosses of PI 567609 with BSR
      susceptible and -resistant genotypes were evaluated for response to BSR-causal
      fungus, Phialophora gregata. Genetic analyses indicated that PI 567609 carries a
      single gene or cluster of linked genes for brown stem rot resistance, and that
      this gene (or cluster) is allelic to, or tightly linked to previously identified
      resistance genes, Rbs1, Rbs2, and Rbs3. Because previous allelism tests indicated
      that Rbs1, Rbs2, and Rbs3 were unlinked, and molecular mapping studies have
      indicated that Rbs1, Rbs2, and Rbs3 are linked on molecular linkage group J of
      soybean, a new model is proposed for BSR resistance. In this model, BSR
      resistance is controlled through the interaction of alleles at four independent
      loci, at least two of which are necessary to condition a resistance response.
      Functional redundancy at three of these loci allows any one of the three to
      interact with a fourth locus to confer resistance to BSR.

PMID- 10912680
TI  - Distorted segregation resulting from pea chromosome reconstructions with alien
      segments from Pisum fulvum.
AB  - Pea (Pisum sativum L.) satellited chromosome reconstructions were analyzed by
      cytologic markers to identify segregation distortion events. The presence of
      modified chromosomes was evaluated on the basis of additional rDNA genes, an
      extra and a longer satellite, all derived from chromosome 5 and chromosome 7 from
      P. fulvum Sibth. & Sm. The segregation of modified satellited chromosome 5 was
      monitored through fluorescent in situ hybridization with rDNA probe; it fitted
      the expected 1:2:1 ratio after self-pollination of a heterozygous genotype for
      modified chromosome 5. In different genotypes, which were heterozygous for both
      modified chromosomes 5 and 7, the combined segregation of these chromosomes
      showed the occurrence of seven karyotype classes instead of the expected nine.
      The classes with modified chromosome 7 and without modified chromosome 5, whether
      heterozygous or homozygous, were absent. The hypothesis of gamete selection was
      rejected since the expected segregation ratio of 5:3:1 was significant by chi
      square test. Based on the other hypothesis of postzygotic selection, the
      segregation ratio did not show a significant deviation from the expected 9:3:1
      ratio, thereby indicating that embryo abortion caused the segregation distortion
      (SD). The hypothesis of the SD system involving two loci carried by the alien
      satellites of modified chromosomes 5 and 7 is discussed in relation to the
      evolution of the P. fulvum genome.

PMID- 10912681
TI  - Chromosomal assignment of microsatellite loci in cotton.
AB  - Microsatellite markers or simple sequence repeats (SSRs) represent a new class of
      genetic markers for cotton (Gossypium sp.). Sixty-five SSR primer pairs were used
      to amplify 71 marker loci and genotype 13 monosomic and 27 monotelodisomic cotton
      cytogenetic stocks. Forty-two SSR loci were assigned to cotton chromosomes or
      chromosome arms. Thirty SSRs were not located to specific chromosomes in this
      study. Nineteen marker loci were shown to occur on the A subgenome and 11 on the
      D subgenome by screening accessions of G. herbaceum (2n = 2x = 26 = 2A1) and G.
      raimondii (2n = 2x = 26 = 2D5). The aneuploid stocks proved to be very powerful
      tools for localizing SSR markers to individual cotton chromosomes. Multiplex PCR
      bins of the SSR primers and semiautomated detection of the amplified products
      were optimized in this experiment. Thirteen multiplex PCR bins were optimized to
      contain an average of 4 SSR primer pairs per bin. This provides a protocol for
      high-throughput genotyping of cotton SSRs that improves the efficiency of genetic
      mapping and marker-assisted programs utilizing SSR markers.

PMID- 10912682
TI  - Quiescent intense (qi): a gene that affects young but not mature fruit color
      intensity in Cucurbita pepo.
AB  - Jack O'Lantern, a cultivar of the pumpkin group of Cucurbita pepo that has
      intense-colored young fruits, was crossed with Vegetable Spaghetti, a cultivar of
      the vegetable marrow group that has light-colored young fruits and genotype d/d I
      1/I-1 I-2/I-2. The F1 plants, regardless of the direction of the cross, had light
      colored young fruits. Young fruit color was observed to segregate in accordance
      with a 3 intense: 13 light ratio in the F2, indicating that two genes, one
      dominant and one recessive, are interacting. By crossing Jack O'Lantern with
      tester stocks of known genotypes, the dominant gene was identified as L-2. The
      recessive gene, previously undescribed, is herein designated quiescent intense
      (qi), as it intensifies young fruit color but was observed to have little or no
      effect on intermediate-age and mature fruit colors. The young fruits of Verte Non
      Coureuse D'Italie, a cultivar of the cocozelle group, are intense-colored. F1
      plants of the cross between this cultivar and Jack O'Lantern had intense-colored
      young fruits, but F1 plants of the cross between this cultivar and Vegetable
      Spaghetti had light-colored young fruits. Therefore both Verte Non-Coureuse
      D'Italie and Jack O'Lantern are qi/qi, while Vegetable Spaghetti is Qi/Qi.

PMID- 10912683
TI  - A new recessive ametapodia mutation in the chicken (Gallus domesticus).
AB  - An apparently new mutation that is associated with abnormal limb development
      appeared in a strain of Light Brown Leghorn chickens. Mutants are characterized
      by the complete absence of the tarsometatarsals, while severely hypoplastic
      development of the metacarpals is also present. The phenotype of the new mutant
      (ametapodia-2) closely resembles ametapodia-1, described in 1967, but ametapodia
      2 is inherited as an autosomal recessive (AMET*A), while ametapodia-1 was
      associated with an incompletely dominant gene (MP*A). Only heterozygous
      ametapodia-1 (MP*N/MP*A) were viable and able to reproduce, while homozygous
      ametapodia-2 mutants do not normally survive beyond 2-4 days of age. The
      shankless mutation (SHL*S) also reduces development of the metatarsal and
      metacarpal bones and has been shown to be associated with a pericentric inversion
      of chromosome 2. No obvious cytologic abnormality was apparent in ametapodia-2
      birds, and offspring of a cross between AMET*A carriers and shankless birds were
      normal, indicating that the two mutations are not alleles. Ametapodia-1 (MP*A)
      was found to be linked to the rose comb locus (R) by 16 crossover units. Linkage
      test matings between AMET*A and (R*R) showed independent segregation, strongly
      suggesting that the mutation occurred at a relatively distant locus and therefore
      is probably not allelic to MP*A.

PMID- 10912684
TI  - Linkage mapping of the ovine alpha-inhibin (INHA) beta(A)-inhibin/activin (INHBA)
      and beta(B)-inhibin/activin (INHBB) genes.
AB  - A full-sib mapping population was typed for Taql Southern blot RFLPs at the ovine
      alpha-inhibin (INHA), beta(A)-inhibin/activin (INHBA), and beta(B)
      inhibin/activin (INHBB) loci. The most likely positions were found by genetic
      linkage analysis. INHA was placed on ovine chromosome 2q, between microsatellite
      markers BM6444 and INRA135, while INHBB was located 39 cM proximal to INHA
      between markers BMS1126 and BMS2626. The INHBA gene, a comparative mapping anchor
      locus, mapped to chromosome 4, between microsatellites OARCP26 and BMS719. These
      data confirm and refine previous chromosomal assignments by in situ
      hybridization, provide comparative mapping information, and identify
      microsatellite markers suitable for QTL association studies with inhibin/activin
      genes in ruminants.

PMID- 10912685
TI  - The hypotrichosis-generating shorn (shn) mutation maps to distal chromosome 7 in
      the Norway rat.
AB  - We have recently identified an autosomal recessive mutation in the Norway rat
      that generates an almost complete absence of normal hair. Here we describe a
      multilocus backcross analysis that was used to map this mutation, named shorn
      (gene symbol shn), to the distal end of rat chromosome 7. Although this region in
      rat carries no previously mapped similar mutations, the homologous genomic
      regions in mouse and human contain several potential homologues and candidate
      genes.

PMID- 10912686
TI  - AUTOTET: a program for analysis of autotetraploid genotypic data.

PMID- 10912687
TI  - Try riding a horse.

PMID- 10912688
TI  - Granular myringitis: is it a surgical problem?
AB  - OBJECTIVE: An attempt to settle the controversies associated with granular
      myringitis (GM) including incidence, etiology, pathology, presentation, relation
      to chronic otitis media, and treatment. STUDY DESIGN: Retrospective. SETTING:
      Tertiary referral center and private otology practice. PATIENTS: 94 patients
      presenting with GM over 28 years. INTERVENTION: Diagnosis by otoscopy,
      audiometry, radiology, and bacteriology; long-term follow-up (6 months to 12
      years); assessment of treatment results. MAIN OUTCOME MEASURES: The pathologic
      states of the affected tympanic membranes were studied in both active and
      quiescent stages. The results of conservative versus surgical management were
      evaluated. RESULTS: The disease presents with chronic painless otorrhea, normal
      hearing and mastoid pneumatization, and granular areas, which may be patchy,
      diffuse, or segmental. The latter is the most frequent and is most commonly
      posterosuperior. The infecting organism is Pseudomonas aeruginosa. The pathologic
      process affects all drum layers and can cause a perforation. The most important
      predisposing factor is disturbed epithelial migration, which may be exaggerated
      by eustachian tube dysfunction. Of 26 cases treated conservatively, none healed
      without recurrence. Of 48 cases treated surgically, there were 2 recurrences.
      CONCLUSIONS: Pathologically, the disease affects all drum layers. It presents
      with an active stage, which may be misdiagnosed as chronic otitis media or
      cholesteatoma, and a quiescent stage when it may be overlooked. Although distinct
      from chronic otitis media, it can cause a perforation. The disease responds
      readily to medical treatment, but recurrence is common. Radical surgery offers a
      curative measure in refractory cases.

PMID- 10912689
TI  - Use of a hyaluronan-based biomembrane in the treatment of chronic
      cholesteatomatous otitis media.
AB  - OBJECTIVE: To test the efficacy and safety of a hyaluronan-based biomembrane in
      stimulating the healing process in patients undergoing tympanomastoid surgery.
      STUDY DESIGN: The trial was an open, two-arm, controlled, randomized,
      prospective, multicenter study conducted at two different hospitals. PATIENTS:
      Sixty subjects (18-65 years of age, both sexes) with chronic cholesteatomatous
      otitis media were enrolled and treated by the "one-stage open technique."
      Efficacy and safety parameters were assessed at 3, 5, 7, 9, 11, 13, 17, 21, and
      25 weeks after surgery. Three sets of composite criteria were considered:
      patient's assessment of quality of healing, otomicroscopy, and audiometry.
      RESULTS: Of the 60 patients, 50 completed the study. Subjects treated with the
      biomembrane had statistically significant better scores than controls (no
      treatment) for all variables considered, excluding audiometry (no significant
      differences). No adverse events occurred in treated patients. CONCLUSION: Data
      demonstrate that the application of a hyaluronan-based biomembrane improves the
      healing of the mastoid cavity following "open" tympanoplasty. In particular, re
      epithelialization was significantly faster after the application of the
      biomembrane. Moreover, the device neither caused any adverse events nor showed
      signs of ototoxicity. Re-epithelialization of open cavities and tympanic grafts
      still represents for surgeons an unpredictable step in the healing process.
      Hyaluronian-derivates may effectively contribute to the reduction of such
      variability.

PMID- 10912690
TI  - Preference for the closed technique in the management of cholesteatoma of the
      middle ear in children: a retrospective study of 215 consecutive patients treated
      over 10 years.
AB  - OBJECTIVES: To evaluate clinical data, extensions, residual and recurrent lesion
      rates, and functional results in cases of cholesteatoma in pediatric patients.
      DESIGN: A retrospective study at a single tertiary care center over a decade.
      PATIENTS: In 199 children (mean age 9.6 years), 215 cholesteatomas were treated
      surgically, and the children were followed up for an average of 70 months (range
      25-118 months). INTERVENTIONS: Therapeutic and rehabilitative surgical procedures
      were done, using either a closed technique (CT) or an open technique:
      tympanoplasty in open technique (TOT), radical mastoidectomy (RM), or Rambo's
      technique) MAIN OUTCOME MEASURES: Surgical findings, residual and recurrent
      lesions rate, and hearing assessment. RESULTS: The first surgical procedure was
      CT in 88% of cases, TOT in 10%, RM and Rambo's technique in 1%. Two operations
      were done in 61.8% of children; 21% had three operations and 4.5% had four.
      Residual lesions were observed in 21.5% of all children, 32.8% in those
      undergoing a planned second look. Recurrence rate was 9.8%. Surprisingly,
      residual and recurrent lesion rates were higher after TOT (23.8% and 19%) than
      after CT (20.5%, 8.9%), but TOT-treated children had much more extensive lesions.
      A speech reception threshold (SRT) <30 dB hearing loss (HL) was achieved in 63.7%
      of patients, and normal hearing was obtained in 12.1%; SRT was significantly
      better after CT (mean 26.7 dB) than after TOT (mean 37.4 dB), after type II (mean
      27 dB) than after type III (35 dB). A high-frequency pure-tone hearing loss >10
      dB was uncommon (7.6%). CONCLUSION: These results support the continued use of CT
      in most cases of cholesteatoma in children in developed countries.

PMID- 10912691
TI  - The effect of topical adrenaline on the development of myringosclerosis after
      tympanostomy tube insertion.
AB  - OBJECTIVE: To determine the effect of topical adrenaline application after
      myringotomy and before tympanostomy tube placement on the development of
      myringosclerosis. STUDY DESIGN: A prospective, randomized, double-blind study,
      with each patient acting as his or her own control. Ethical approval and full
      parental consent were obtained. SETTING: Department of Otorhinolaryngology-Head
      and Neck Surgery in a university teaching hospital. PATIENTS: Fifty children
      satisfying inclusion and exclusion criteria for first-time tympanostomy tube
      insertion. THERAPEUTIC INTERVENTION: Myringotomy followed by adrenaline
      application to incision before tympanostomy tube insertion. Control contralateral
      ear received saline application after myringotomy. Follow-up examination was done
      14 to 21 days after surgery and again after 1 year by a single blinded surgeon.
      MAIN OUTCOME MEASURE: Comparison of myringosclerosis between adrenaline-treated
      ears and matched control ears. RESULTS: No difference was found in early
      morbidity between the two groups of ears. Myringosclerosis after 1 year was not
      found to have been significantly affected by adrenaline application (p = 0.2)
      CONCLUSION: The use of adrenaline on the myringotomy site before tympanostomy
      tube placement was not found to influence early postoperative morbidity or the
      later development of myringosclerosis.

PMID- 10912692
TI  - Attic aeration in temporal bones from children with recurring otitis media:
      tympanostomy tubes did not cure disease in Prussak's space.
AB  - HYPOTHESIS: Blockage of the aeration pathways to the attic may cause
      circumscribed or widespread alterations that are difficult to diagnose
      clinically. The narrow route via the posterior pouch to Prussak's space is
      especially vulnerable to obstruction in recurring otitis media. BACKGROUND:
      Recent studies of the epitympanic diaphragm and compartments have clarified the
      anatomy of the attic aeration and drainage pathways and emphasized the role of
      their patency in the healing process of middle ear infections. In neonatal otitis
      media, the amniotic fluid cellular content (AFCC) has proved to be a good
      indicator in outlining the areas where inflammation products concentrate,
      possibly causing early blockage of ventilation. METHODS: Twenty-eight temporal
      bones from 14 children were studied; 4 of these children had experienced
      bilateral recurring otitis media. In the latter group, 1 ear was studied by
      microdissection and the other by serial sectioning. RESULTS: Prussak's space was
      involved in all 4 pairs of bones and either contained thick mucus, contained
      secretion in the process of organization, or was obliterated. The tympanic
      isthmus was fully obstructed in 1, partially blocked in 2, and open in 5
      specimens. CONCLUSIONS: If a thick mature connective tissue mass develops under
      the epidermal layer of Shrapnell's membrane during an obliteration process of
      Prussak's space, the condition may stay stable and benign. Severe retraction of
      Shrapnell's membrane represents a likely forerunner of a retraction pocket
      cholesteatoma. Systematic otomicroscopy allows early detection, and cure can be
      achieved by minor surgery. In some children, despite the treatment of recurring
      otitis media with ventilation tubes, the attic and mastoid can be extensively
      involved, necessitating atticomastoidectomy and the creation of new pathways for
      attic aeration.

PMID- 10912693
TI  - Magnetic resonance imaging of stapes prostheses.
AB  - OBJECTIVE: To assess the magnetic resonance imaging (MRI) compatibility of stapes
      prostheses. DATA SOURCES: A comprehensive review of the English literature
      evaluating MRI compatibility of stapes prostheses. Multiple series of stapes
      prostheses from different manufactures placed in a 1.5-tesla MRI field to
      determine ferromagnetic properties. RESULTS: When MRI was first introduced,
      reports demonstrated the MRI compatibility of stapes prostheses. The testing was
      performed on single copies of various prostheses from several manufacturers.
      Although implant manufacturers have indicated MRI compatibility, several reports
      of variable ferromagnetic properties of aneurysm clips have been reported. This
      variability has led to rotation of the clips and hemorrhage in patients with
      supposed MRI-compatible clips. These findings suggest that testing single stapes
      prostheses from a manufacturer might not completely assess the safety of MRI on
      patients with stapes prostheses. We performed MRI compatibility testing on
      several series of stapes prostheses from Xomed Surgical Products and Smith &
      Nephew Richards. Two series of Xomed stapes prostheses were found to have
      ferromagnetic properties. CONCLUSION: Manufacturing variability could lead to
      stapes prostheses being MRI incompatible. Each prosthesis should be tested before
      implantation for ferromagnetic properties.

PMID- 10912694
TI  - Intratympanic immunosuppressives for prevention of immune-mediated sensorineural
      hearing loss.
AB  - HYPOTHESIS: Round window membrane application of immunosuppressives reduces
      cochlear inflammation and hearing loss in a guinea pig model of sterile
      labyrinthitis. BACKGROUND: Systemic immunosuppressives are used to treat
      sensorineural hearing loss due to inflammation (autoimmune, bacterial, viral),
      which in animal models causes hearing loss. Transtympanic application of drugs is
      an attractive and possibly efficacious method of treatment that avoids systemic
      toxicities. METHODS: Sterile labyrinthitis was created using keyhole limpet
      hemocyanin (KLH). Dexamethasone (0.048 mg/day and 0.288 mg/day), cyclosporine
      (0.5%), prednisolone acetate (1%), fluorouracil, (5%), and FK506 (0.01%) were
      delivered to the round window membrane with one injection (filling middle ear
      space) or osmotic minipumps. Efficacy was evaluated by auditory brainstem
      response and histology. RESULTS: No drug was effective at reducing hearing loss
      or inflammation. CONCLUSION: Local application of immunosuppressives did not
      suppress inner ear inflammatory infiltrates and hearing loss in KLH-induced
      labyrinthitis in a guinea pig model.

PMID- 10912695
TI  - Degeneration in the cochlea after noise damage: primary versus secondary events.
AB  - PURPOSE: To determine if noise damage in the organ of Corti is different in the
      low- and high-frequency regions of the cochlea. MATERIALS AND METHODS:
      Chinchillas were exposed for 2 to 432 days to a 0.5 (low-frequency) or 4 kHz
      (high-frequency) octave band of noise at 47 to 95 dB sound pressure level.
      Auditory thresholds were determined before, during, and after the noise exposure.
      The cochleas were examined microscopically as plastic-embedded flat preparations.
      Missing cells were counted, and the sequence of degeneration was determined as a
      function of recovery time (0-30 days). RESULTS: With high-frequency noise,
      primary damage began as small focal losses of outer hair cells in the 4-8 kHz
      region. With continued exposure, damage progressed to involve loss of an entire
      segment of the organ of Corti, along with adjacent myelinated nerve fibers. Much
      of the latter loss is secondary to the intermixing of cochlear fluids through the
      damaged reticular lamina. With low-frequency noise, primary damage appeared as
      outer hair cell loss scattered over a broad area in the apex. With continued
      exposure, additional apical outer hair cells degenerated, while supporting cells,
      inner hair cells, and nerve fibers remained intact. Continued exposure to low
      frequency noise also resulted in focal lesions in the basal cochlea that were
      indistinguishable from those resulting from exposure to high-frequency noise.
      CONCLUSIONS: The patterns of cochlear damage and their relation to functional
      measures of hearing in noise-exposed chinchillas are similar to those seen in
      noise-exposed humans. Thus, the chinchilla is an excellent model for studying
      noise effects, with the long-term goal of identifying ways to limit noise-induced
      hearing loss in humans.

PMID- 10912696
TI  - Meningeal carcinomatosis manifested as bilateral progressive sensorineural
      hearing loss.
AB  - OBJECTIVE: Meningeal carcinomatosis is defined as the diffuse infiltration of the
      leptomeninges and subarachnoid space by malignant cells metastasizing from
      systemic cancer. The authors describe a rare case of meningeal carcinomatosis
      initially appearing as bilateral progressive sensorineural hearing loss. PATIENT:
      A 57-year-old man with lung cancer was referred to the authors' clinic because of
      progressive hearing loss, tinnitus, dizziness, and blurred vision for 1 month.
      RESULTS: Magnetic resonance imaging revealed abnormal leptomeningeal enhancement.
      Meningeal carcinomatosis was diagnosed by the detection of malignant cells in the
      cerebrospinal fluid after lumbar puncture. The patient died 1 year after
      diagnosis. CONCLUSIONS: Meningeal carcinomatosis must be considered in the
      differential diagnosis in cancer patients with bilateral progressive
      sensorineural hearing loss. Gadolinium-enhanced magnetic resonance imaging is a
      useful complementary diagnostic tool before lumbar puncture.

PMID- 10912697
TI  - Effect of protective agents against cisplatin ototoxicity.
AB  - HYPOTHESIS: The goals of this investigation were to compare the efficacy of three
      protective agents against cisplatin-induced elevation of auditory brainstem
      response (ABR) thresholds and to examine whether these protective agents prevent
      cisplatin-induced alterations of the antioxidant defense system in the cochlea of
      the rat. BACKGROUND: Cisplatin is an ototoxic antitumor agent. Previous animal
      studies have shown that cisplatin administration causes an elevation of ABR
      thresholds. These auditory changes are accompanied by alterations in the
      concentration of glutathione and the antioxidant enzymes in the cochlea. The
      authors' previous work has indicated that the protective agent
      diethyldithiocarbamate (DDTC) prevents decrease in glutathione (GSH), alteration
      of antioxidant enzyme activity, and disruption of cochlear function with
      cisplatin administration. METHODS: Wistar rats were sedated and underwent
      pretreatment ABR testing using clicks and tone burst stimuli at 8, 16, and 32
      kHz. Control rats received saline by intraperitoneal (i.p.) injection. Positive
      control rats were administered cisplatin 16 mg/kg i.p. Three groups of rats
      received protective agents in combination with cisplatin. The DDTC-protected rats
      were given 600 mg/kg of DDTC subcutaneously 1 hour after cisplatin. Animals
      protected by 4-methylthiobenzoic acid (MTBA) were given 250 mg/kg of this agent
      i.p. 30 minutes before cisplatin. Animals protected with ebselen were given 16
      mg/kg i.p. one hour before cisplatin. The ABR thresholds were recorded 72 hours
      after cisplatin administration in all groups. Cochleas were removed, and extracts
      of the tissues were analyzed for GSH, activities of antioxidant enzymes
      (superoxide dismutase [SOD], catalase, glutathione peroxidase, and glutathione
      reductase) and malondialdehyde (MDA) (as an index of lipid peroxidation).
      RESULTS: Cisplatin-treated rats had significant ABR threshold shifts, ranging
      from 27 to 40 dB. Rats administered each of the three protective agents in
      combination with cisplatin had ABR threshold shifts of <10 dB. The cochleae of
      rats administered cisplatin alone had nearly a 50% depletion of glutathione and
      about a 50% reduction in the activities of SOD, glutathione peroxidase, and
      glutathione reductase, while catalase activity was reduced to 70% of control
      values. These changes were accompanied by a reciprocal elevation of MDA of 165%.
      These changes, namely, the depletion of GSH and antioxidant enzyme activity and
      the elevation of MDA in the cochlea, were largely attenuated by the
      administration of the protective agents tested. CONCLUSION: These findings
      suggest that cisplatin ototoxicity is related to lipid peroxidation and that the
      use of protective agents prevents hearing loss and lipid peroxidation by sparing
      the antioxidant system in the cochlea. These results suggest the possibility that
      the clinical use of protective agents could effectively reduce or prevent damage
      to the inner ear of patients receiving cisplatin chemotherapy, provided that the
      antitumor effect is not altered.

PMID- 10912698
TI  - Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic
      emissions in laboratory animals.
AB  - OBJECTIVE: The role of transient evoked otoacoustic emissions (TEOAE) and
      distortion product otoacoustic emissions (DPOAE) as early indicators of cisplatin
      induced ototoxicity in three different rodent species--the guinea pig. the albino
      rat, and the fat sand rat (Psammomys obesus)--was investigated. In addition, an
      attempt was made to determine which of the three rodent species is most
      susceptible to cisplatin-induced ototoxicity as measured by auditory brainstem
      responses (ABR), BACKGROUND: There have been numerous clinical and experimental
      reports on cisplatin-induced ototoxicity, but to the authors' best knowledge,
      there has been no comparative report on the short-term effects of cisplatin on
      OAE measured with commercially available equipment between different rodent
      species. METHODS: Cisplatin was systemically administered as a single high dose
      (12 mg/kg intraperitoneally) to all three species, and the ototoxic effects were
      measured before and 3 days after the injection of cisplatin in the same animals,
      using ABR, TEOAE, and DPOAE. RESULTS: The ABR thresholds were significantly
      elevated in the guinea pigs and the albino rats but not in the sand rats.
      Significant depression of TEOAE energy and DPOAE amplitude occurred only in the
      guinea pigs. The depression of the DPOAE was greater than that of the TEOAE. The
      guinea pigs showed the greatest degree of ototoxicity (depression of ABR and
      OAE). CONCLUSIONS: Among the three rodent species, the guinea pig has the
      potential to be used as a sensitive animal model in studies of cisplatin
      ototoxicity. The study also showed that the recordings of TEOAE and DPOAE, in
      addition to ABR, are sensitive techniques for the assessment of cisplatin-induced
      ototoxicity.

PMID- 10912699
TI  - Preoperative cochlear implant imaging: is magnetic resonance imaging enough?
AB  - OBJECTIVE: To investigate the accuracy of magnetic resonance imaging (MRI) as a
      preoperative imaging technique for cochlear implant candidates. STUDY DESIGN:
      Retrospective, blinded. SETTING: Tertiary medical center. PATIENTS: 31 cochlear
      implant candidates with various causes of hearing loss. INTERVENTION: Cochlear
      implant patients received preoperative high-resolution temporal bone computed
      tomography (CT), and high-resolution T2-weighted fast spin echo MRI (FSE-MRI).
      The images were read independently of each other and in a blinded manner by two
      neuroradiologists. The imaging results were also correlated with intraoperative
      findings. MAIN OUTCOME MEASURES: Lack of agreement between the findings for
      either imaging technique; also, lack of agreement between imaging findings and
      intraoperative findings. RESULTS: FSE-MRI is equal to CT imaging in the detection
      of abnormalities of cochlear patency. It is better than CT imaging in detecting
      cochlear dysplasia and large vestibular aqueducts, and in determining the
      presence of the cochlear nerve. CONCLUSION: FSE-MRI is accurate in predicting
      inner ear anomalies and obstruction of the cochlear lumen. It also adds
      information not gathered from CT imaging, such as the presence and size of the
      cochlear nerve.

PMID- 10912700
TI  - Electrocochleography and gentamicin therapy for Meniere's disease: a preliminary
      report.
AB  - OBJECTIVE: It is widely held that an enlarged summating potential (SP) relative
      to the eighth nerve action potential (AP) is a reflection of endolymphatic
      hydrops. Aminoglycosides are an accepted treatment for incapacitating Meniere's
      disease and are known to affect both sensory and secretory cells of the inner
      ear. The intent of this study was to determine whether this effect on secretory
      cells could be objectively confirmed by virtue of changes in the
      electrocochleogram (ECoG) of patients receiving gentamicin therapy for Meniere's
      disease. STUDY DESIGN: This was a prospective longitudinal study of repeated ECoG
      measures in three groups of subjects. Meniere's patients undergoing gentamicin
      treatment were compared with two control groups: individuals with stable
      Meniere's disease and normal-hearing control subjects. SETTING: The study was
      conducted at a tertiary referral center. PATIENTS: The sample included 21 normal
      hearing subjects, 15 patients with stable unilateral Meniere's disease, and 12
      with disabling unilateral Meniere's disease. INTERVENTIONS: For patients with
      disabling Meniere's disease, gentamicin was administered transtympanically.
      Audiograms, impedance tests, and ECoG were performed twice for all subjects. MAIN
      OUTCOME MEASURES: The SP and AP amplitudes, AP latency, and SP/AP ratio of the
      EcoG were measured. RESULTS: A statistically significant reduction in the SP/AP
      ratio was observed after gentamicin administration (analysis of variance
      interaction effect: F2 = 5.64; p = 0.0065). CONCLUSIONS: The significant
      reduction in the SP/AP ratio in the gentamicin-treated Meniere's group supports
      the hypothesis that gentamicin improves the electrophysiologic function of the
      cochlea, possibly by reducing the severity of the associated endolymphatic
      hydrops.

PMID- 10912701
TI  - Outcome analysis of individualized vestibular rehabilitation protocols.
AB  - OBJECTIVE: To determine the outcome of vestibular rehabilitation protocols in
      subjects with peripheral vestibular disorders compared with normal and abnormal
      control subjects. STUDY DESIGN: Prospective study using repeated measure, matched
      control design. Subjects were solicited consecutively according to these
      criteria: vestibular disorder subjects who had abnormal results of computerized
      dynamic posturography (CDP) sensory organization tests (SOTs) 5 and 6 and
      underwent rehabilitation; vestibular disorder subjects who had abnormal results
      of SOTs 5 and 6 and did not undergo rehabilitation; and normal subjects (normal
      SOTs). SETTING: Tertiary neurotology clinic. SUBJECTS: Men and women over age 18
      with chronic vestibular disorders and chief complaints of unsteadiness,
      imbalance, and/or motion intolerance, and normal subjects. INTERVENTIONS: Pre-
      and post-rehabilitation assessment included CDP, vestibular disability, and
      activities of daily living questionnaires. Individualized rehabilitation plans
      were designed and implemented to address the subject's specific complaints and
      functional deficits. Supervised sessions were held at weekly intervals, and self
      administered programs were devised for daily home use. MAIN OUTCOME MEASURES: CDP
      composite and SOT scores, number of falls on CDP, and self-assessment
      questionnaire results. RESULTS: Subjects who underwent rehabilitation (Group A)
      showed statistically significant improvements in SOTs, overall composite score,
      and reduction in falls compared with abnormal (Group B) control groups. Group A's
      performances after rehabilitation were not significantly different from those of
      normal subjects (Group C) in SOTs 3 through 6, and close to normal on SOTs 1 and
      2. Subjects in Group A also reported statistically significant symptomatic
      improvement. CONCLUSIONS: Outcome measures of vestibular protocol physical
      therapy confirmed objective and subjective improvement in subjects with chronic
      peripheral vestibular disorders. These findings support results reported by other
      investigators.

PMID- 10912702
TI  - Results of serial vestibular testing in unilateral Meniere's disease.
AB  - OBJECTIVE: To determine the prevalence and character of vestibular abnormalities
      and the changes in vestibular function that occur in unilateral Meniere's
      disease. STUDY DESIGN: Retrospective case review. SETTING: Ambulatory patients at
      a tertiary care facility. PATIENTS: Entry criteria included a diagnosis of
      unilateral Meniere's disease and test results from at least two vestibular test
      sessions at the Johns Hopkins Otologic Vestibular Laboratory. One hundred twenty
      two cases were evaluated. MAIN OUTCOME MEASURES: Electronystagmographic
      evaluation, including caloric testing; audiometric tests; and medical records.
      RESULTS: Caloric weakness was demonstrated in 58% of patients on the involved
      side and in 19% on the normal side. Complete paralysis was found in 7%.
      Directional preponderance was seen in 33% of patients and completely normal
      scores in 27%. During the course of the disease, responses become weaker in 26%
      of patients and stronger in 11%. Of 39 patients tested more than twice, 26%
      showed both increases and decreases in caloric responses. After an acute attack,
      only one of eight patients showed a depressed response on the diseased side, and
      three showed an increased response. Spontaneous nystagmus, seen within 24 hours
      of an attack in 54 cases, was directed away from the diseased ear in only about
      one half of the cases. Benign paroxysmal positional vertigo was found in 44% of
      these patients. CONCLUSIONS: Possible pathophysiologic explanations for the
      various test results in Meniere's disease are discussed. Interpretation of
      caloric test results should take into account the absolute value of the slow
      phase eye speed scores, in addition to the right-left difference score. Also,
      established standards for the normal range of fluctuation in both absolute and
      comparative scores should be used when more than one test session has been
      undertaken.

PMID- 10912703
TI  - Isolated directional preponderance of caloric nystagmus: I. Clinical
      significance.
AB  - OBJECTIVES: To determine the clinical significance of an isolated directional
      preponderance (DP) on bithermal caloric testing. An isolated caloric DP was
      defined as a DP, calculated according to the standard Jongkees formula, of > or =
      40%, with a spontaneous nystagmus (SN) in darkness of < or = 2 degrees/s and a
      canal paresis (unilateral weakness) of < or = 25%. STUDY DESIGN: A retrospective
      analysis of all 15,542 bithermal caloric tests performed in the authors'
      department in the previous 10 years to identify all tests with an isolated DP of
      > or = 40%. This was followed by a review of the clinical data on the 144
      patients identified with such a result and then by a telephone or postal follow
      up study of these patients. The study group eventually comprised 114 patients;
      these were patients in whom a clinical diagnosis could be made at the time the
      caloric test was done, or who responded to requests for follow-up information.
      The 34 patients in whom a clinical diagnosis could not be made at the time of the
      caloric test, and who did not respond to requests for follow-up information, were
      excluded. STUDY SETTING: A balance disorders clinic in a tertiary referral
      hospital. INTERVENTION: All patients underwent standard bithermal caloric
      testing. Some of the patients also underwent rotational testing. OUTCOME
      MEASURES: A clinical diagnosis for the cause of the isolated DP, made either at
      the time of the caloric test or on the basis of information supplied at follow-up
      by the patient or by the referring physician. RESULTS: Of 114 patients, 39 had
      benign paroxysmal positioning vertigo, 14 had Meniere's disease, and 5 had
      migrainous vertigo. Five patients had central nervous system (CNS) disorders, and
      this was clinically apparent at the time of the caloric test in 4, so that only 1
      patient with an isolated DP developed evidence of a CNS disorder after the
      caloric test was done. In the other 54 patients, no definite diagnosis could be
      made, but 41 of these 54 were either completely well or much better at follow-up.
      CONCLUSIONS: An isolated DP on caloric testing is usually a transient, benign
      disorder. About half the patients with an isolated DP have either Meniere's
      disease or benign paroxysmal positioning vertigo; in most of the other half, no
      definite diagnosis is made but most of these patients will do well. Only
      approximately 5% have a CNS lesion and in almost all this is apparent at the time
      the caloric test is done. In a relapsing-remitting peripheral vestibular disorder
      such as benign paroxysmal positioning vertigo or Meniere's disease, the mechanism
      of an isolated DP could be enhanced dynamic gain of ipsilesional medial
      vestibular nucleus neurons, perhaps as a result of intermittent hyperfunction of
      primary semicircular canal vestibular afferents. The authors postulate that an
      isolated DP reflects a gain asymmetry between neurons in the medial vestibular
      nucleus on either side, caused either by increased sensitivity on one side or by
      reduced sensitivity on the other, perhaps as an adaptive change in response to
      abnormal input. In an accompanying article, the authors implement a realistic
      neural network model in which it is possible to simulate an isolated DP by
      adjusting the dynamic sensitivity of type 1 medial vestibular nucleus neurons on
      one side or of type 2 medial vestibular nucleus neurons on the other.

PMID- 10912704
TI  - Isolated directional preponderance of caloric nystagmus: II. A neural network
      model.
AB  - HYPOTHESIS: The purpose of this study was to simulate an isolated directional
      preponderance (DP) on bithermal caloric testing by constructing a realistic
      neural network model. The simulation was designed to capture not only the
      characteristics of the nystagmus response to caloric stimulation but also the
      response to rotational stimulation in patients with an isolated caloric DP.
      BACKGROUND: The nature of an isolated DP--that is, a DP in the absence of a
      significant spontaneous nystagmus or canal paresis--is outlined in the preceding
      article. In this article, the authors investigate the possible neural basis for
      an isolated caloric DP using the mathematic modeling technique of neural network
      simulation. Neural network models are typically abstract in nature; however, in
      this case the network was based on the known structure and function of the
      central vestibular system. METHODS: The neural network model was based on the
      known neuroanatomy and neurophysiology of the horizontal vestibuloocular reflex
      pathway. A leftward-rightward asymmetric modification of the dynamic responses of
      simulated medial vestibular nucleus type IA neurons on one side, or of type 2
      neurons on the other side, to peripheral input would generate an isolated caloric
      DP. RESULTS: The values of DP and associated canal paresis produced by the
      network were within the same range as in the patient group. The network also
      predicted that the rotational DP would be lower than the caloric DP: between 2.5%
      and 56.9% of the caloric DP value. The actual rotational DP value was between 3%
      and 57% (average 41%) of the corresponding caloric DP value. CONCLUSIONS: An
      isolated caloric DP can be simulated by a neural network model by modifying the
      activity of model units that represent medial vestibular nucleus neurons. An
      asymmetric dynamic response by a gain-enhancement function of either type 1A
      neurons on one side or of type 2 neurons on the other was sufficient to produce
      an isolated caloric DP. Excitatory gain enhancement of type 2 neurons produced a
      smaller rotational DP than a similar modification of type 1 neurons. This result
      indicates a potential neural locus for the generation of an isolated DP in
      patients with vestibular disorders.

PMID- 10912705
TI  - Lesions of the internal auditory canal and cerebellopontine angle in an only
      hearing ear: is surgery ever advisable?
AB  - OBJECTIVE: To define the indications for surgery in lesions of the internal
      auditory canal (IAC) and cerebellopontine angle (CPA) in an only hearing ear.
      STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center.
      PATIENTS: Seven patients with lesions of the IAC and CPA who were deaf on the
      side opposite the lesion. Five patients had vestibular schwannoma (VS), and one
      each had meningioma and progressive osseous stenosis of the IAC, respectively.
      The opposite ear was deaf from three different causes: VS (neurofibromatosis type
      2 [NF2]), sudden sensorineural hearing loss, idiopathic IAC stenosis.
      INTERVENTION(S): Middle fossa removal of VS in five, retrosigmoid resection of
      meningioma in one, and middle fossa IAC osseous decompression in one. MAIN
      OUTCOME MEASURE: Hearing as measured on pure-tone and speech audiometry. RESULTS:
      Preoperative hearing was class A in four patients, class B in two, and class C in
      one. Postoperative hearing was class A in three patients, class B in one, class C
      in two, and class D in one. CONCLUSIONS: Although the vast majority of
      neurotologic lesions in an only hearing ear are best managed nonoperatively, in
      highly selected cases surgical intervention is warranted. Surgical intervention
      should be considered when one or more of the following circumstances is present:
      (1) predicted natural history of the disease is relatively rapid loss of the
      remaining hearing, (2) substantial brainstem compression has evolved (e.g., large
      acoustic neuroma), and/or (3) operative intervention may result in improvement of
      hearing or carries relatively low risk of hearing loss (e.g., CPA meningioma).

PMID- 10912706
TI  - Squamous cell carcinoma of the external auditory canal: an evaluation of a
      staging system.
AB  - OBJECTIVE: The study was conducted to review a staging system proposed by the
      University of Pittsburgh for temporal bone cancer and to evaluate survival status
      according to stage, treatment, and certain prognostic factors. STUDY DESIGN: The
      study was a retrospective case review. SETTING: The study was conducted at a
      tertiary care medical center and specialty hospital. PATIENTS: Thirty-two
      patients with primary squamous cell carcinoma of the external auditory canal were
      studied. INTERVENTION: All patients underwent surgery of the temporal bone.
      Radiotherapy was given depending on tumor stage and histopathologic findings.
      MAIN OUTCOME MEASURES: The 2-year survival rates of patients undergoing surgical
      resection with or without adjuvant radiotherapy. RESULTS: The 2-year survival
      rates for primary squamous cell carcinoma of the temporal bone were as follows:
      T1 lesions 100%, T2 80%, T3 50%, and T4 7%. Survival for T3 tumors was 75% with
      postoperative radiotherapy, compared with 0% with surgery alone. CONCLUSIONS: The
      2-year survival data directly correlated with the staging system. The use of
      adjuvant radiotherapy increased survival rate in patients with a T3 lesion.

PMID- 10912707
TI  - Computerized medical record in a private neurotology practice.
AB  - OBJECTIVE: To develop a computerized medical record for a private neurotology
      practice using a relational database with templates. BACKGROUND: Computers have
      been used in the medicine many years for billing, scheduling appointments, and
      word processing. Neurotology represents a relatively narrow field of medicine,
      which is particularly suited to a computerized record. A computerized medical
      record should allow for better data storage and retrieval as well as better
      documentation of the patient care given. METHODS: Using a commercially available,
      record-keeping software in a local area computer network. templates were
      developed for several common neurotologic problems. A template for a neurotologic
      examination was also developed. These were adapted from templates developed by a
      group otolaryngology practice in a neighboring city. Data entry templates for
      vestibular and audiologic tests were also developed. Implementation of the
      computerized record was accomplished in phases, allowing elimination of the paper
      record. RESULTS: A fully computerized medical record has been developed and
      maintained in a private neurotology practice over the past year. Patient response
      to the computerized record system has been favorable. Office personnel have
      adapted well to a paperless record, and referring physicians have welcomed the
      documents generated by the computer. CONCLUSION: Computerizing the medical
      records of a neurotology practice is possible and allows for improved
      documentation, ongoing assessment of treatment results, and improved efficiency
      among office staff.

PMID- 10912708
TI  - Cystic vestibular schwannoma.

PMID- 10912709
TI  - Chondroblastoma of temporal bone.

PMID- 10912710
TI  - Unilateral cleft lip repair--state of the art.
AB  - OBJECTIVE: A number of surgical techniques are utilized to correct the unilateral
      cleft lip, including variations of the rotation-advancement technique. This
      attests to the variability of the original deformity and the esthetic and
      functional results from any one technique, especially those based on traditional
      geometric rearrangement of the skin and associated tissues. RESULTS: Most recent
      advances in cleft lip repair have occurred in two main areas. The morphological
      result has been improved by functional muscular reconstruction of the lip with or
      without orthopedic molding. Early correction of the nasal deformity has also been
      readvocated based on newer principles with excellent results demonstrated.
      CONCLUSION: Further work continues in these areas and improved outcomes will
      continue to be seen along with a clearer understanding of surgical affects on
      growth and development.

PMID- 10912711
TI  - Repair of bilateral complete cleft lip and nasal deformity--state of the art.
AB  - OBJECTIVE: Dissatisfaction with the stigmata of repaired bilateral cleft lip has
      stimulated surgeons to change conventional operative strategies. The old staged
      labial repairs, one side and later the other, have been replaced by simultaneous
      closure. For nasal correction, most surgeons no longer believe that the columella
      is deficient, and thus there is no need to recruit tissue from the lip or nostril
      sills as a secondary procedure. The columella is concealed in the nose. The new
      strategy is to construct the columella and nasal tip by anatomic positioning of
      the alar cartilages and sculpting the investing skin. Furthermore, nasal
      correction is done at the time of bilateral labial repair and, whenever possible,
      the alveolar clefts are closed as well. The goal is primary repair of the primary
      palate. CONCLUSION: Although the principles of synchronous repair of the
      bilateral complete cleft lip and nasal deformity are established, the techniques
      continue to evolve. Bilateral nasolabial repair requires continual study of three
      dimensional form and fourth-dimensional changes that are normal and altered by
      the deformity. Every surgeon who lifts a knife to care for these children has an
      obligation to periodically assess outcome.

PMID- 10912713
TI  - Standardization of 3-D CT measurements for length and angles by matrix
      transformation in the 3-D coordinate system.
AB  - OBJECTIVE: We attempted to establish a new 3-D cephalometry with helical computed
      tomography (CT) by introducing the matrix transformation of the 3-D coordinate
      system. SUBJECTS AND METHODS: Three-dimensional cephalometric landmarks on the
      craniofacial bones were expressed as 3-D vectors originating from the center of
      the sella. These vectors were standardized by the matrix transformation so that
      the midsagittal plane and cranial base line coincided with the XZ plane and X
      axis of the 3-D coordinate system, respectively. We also applied this new method
      to trace the normal growth of the craniofacial bones in 44 patients with head and
      neck cancer (age range, 5 to 26 years; 19 women and 25 men). RESULTS: The
      accuracy for length measurements was less than 3% of standard error of means with
      a slice thickness of 1 or 3 mm for 28 out of the 29 length measurements recorded.
      The precision errors by repeated measurements were 0.8% to 1.0% coefficients of
      variation for intra- and interobserver variability. Standardization of 3-D
      vectors representing the cephalometric landmarks allowed us to assess
      successfully the age-related transition of these landmarks of the patients'
      craniofacial bones. CONCLUSION: A new assessment method for 3-D CT cephalometry
      has been developed by standardizing cephalometric landmarks using a matrix
      transformation of the 3-D coordinate system. This new assessment method may offer
      potential in planning plastic and reconstructive surgery.

PMID- 10912714
TI  - Linkage analysis of candidate regions in Swedish nonsyndromic cleft lip with or
      without cleft palate families.
AB  - OBJECTIVE: To analyze linkage of five candidate regions for nonsyndromic cleft
      lip with or without palate (CLP) on chromosome 2p13, 4q, 6p23, and 19q13; in
      addition chromosome 1q32, the locus for van der Woude syndrome, on Swedish CLP
      families. DESIGN: Three to five linked microsatellite markers were selected from
      each candidate region. Polymerase chain reaction (PCR) with fluorescent-labeled
      microsatellite markers was performed on DNA samples from the participating
      families. Electrophoresis of the PCR products was performed on a laser
      fluorescent DNA sequencer. The genotype data were analyzed with multipoint
      linkage analysis. Modes of inheritance tested included two autosomal dominant, an
      autosomal recessive, and a nonparametric model. Multipoint logarithm of odds
      (LOD) scores were also calculated by assuming genetic heterogeneity.
      PARTICIPANTS: Nineteen Swedish multigenerational families with at least two first
      degree relatives affected with CLP. Greater than 50% of the families studied show
      vertical transmission of the clefting phenotype and both inter- and intrafamilial
      variability were noted. RESULTS: Cumulative multipoint LOD scores for the whole
      group of families calculated under autosomal dominant modes of inheritance were
      negative in all regions and less than -2 except chromosome 6p23. LOD scores
      calculated under recessive inheritance and the nonparametric model were
      inconclusive. There was no significant evidence of genetic heterogeneity among
      the sample group. CONCLUSIONS: The group of Swedish CLP families did not
      demonstrate significant linkage to any of the five candidate regions examined.
      This might suggest a new but yet unknown CLP locus or loci in this family group.
      However, because linkage could not be excluded in some individual families, they
      should still be tested with candidate genes from these regions.

PMID- 10912715
TI  - The relationship between temporal aspects of oral-nasal balance and
      classification of velopharyngeal status in speakers with cleft palate.
AB  - OBJECTIVE: The purpose of this investigation was to determine whether temporal
      patterns of oral-nasal balance differentiate speakers with cleft palate who
      exhibit adequate and inadequate velopharyngeal function. DESIGN: The Nasal
      Accelerometric Vibrational Index (NAVI) was used to measure the time course and
      amplitude of oral-nasal balance during the productions of syllables, words, and
      sentences. The measures obtained include mean amplitude, time integral (area
      under the curve), absolute duration, relative duration, rise time, and fall time.
      PARTICIPANTS: The subjects for this study were 20 children with repaired cleft
      palates with or without cleft lip. Ten children (aged 5 through 18 years) were
      assigned to the velopharyngeal competence (VPC) group (normal oral-nasal
      resonance, no nasal emission of air). Ten children (aged 3 through 19) were
      assigned to the velopharyngeal insufficiency (VPI) group (hypernasal speech,
      velopharyngeal gap observed via nasal endoscopy). RESULTS: Both mean amplitude
      and time integral of NAVI were greater in the VPI group than in the VPC group (p
      < .01). Absolute duration and relative duration of the NAVI signal were greater
      in the VPI group (p < .01). NAVI rise time was shorter in the VPI group (p <
      .01), and NAVI fall time was longer in the VPI group (p < .01). The amplitude
      measures contributed the most to discrimination of speaker group, but the
      durational measures become increasingly influential as a function of a speech
      task. CONCLUSIONS: Although amplitude of nasalization may have the strongest
      perceptual salience in classification of velopharyngeal status, the temporal
      component may exert greater influence during more complex speech tasks.

PMID- 10912716
TI  - Age-related changes in intracranial pressure in rabbits with uncorrected familial
      coronal suture synostosis.
AB  - OBJECTIVE: Chronic, elevated intracranial pressure (ICP) in craniosynostotic
      infants may result in ocular and neurocapsular problems; however, not all infants
      exhibit elevated ICP. Clinical ICP studies are further confounded by small and
      heterogeneic samples, multiple-suture involvement, and varying surgical
      management protocols. The present study was designed to describe longitudinal
      changes in ICP in a large, homogenous sample of rabbits with uncorrected
      familial, nonsyndromic coronal suture synostosis. METHODS: Ninety-one rabbits
      were divided into four groups: (1) normal rabbits (n = 28), (2) rabbits with
      delayed-onset coronal suture synostosis (DOCS; n = 25), (3) rabbits with
      unilateral coronal suture synostosis (UCS; n = 12), and (4) rabbits with
      bilateral coronal suture synostosis (BCS; n = 26). ICP was measured at 24 and 42
      days of age using a Codman epidural microtransducer. RESULTS: Rabbits with BCS
      had a significantly (p < .05) higher mean ICP at 25 days of age than rabbits in
      the other three groups by approximately 146%. However, by 42 days of age, mean
      ICP in normal control rabbits and rabbits with DOCS was significantly (p < .01)
      increased compared with their mean ICP values seen at 25 days of age, while mean
      ICP in BCS rabbits significantly (p < .01) decreased (by 32%) over the same time
      period. ICP in rabbits with UCS was between that seen in normal control rabbits
      and rabbits with BCS and did not significantly (p > .05) change over time.
      CONCLUSIONS: These findings suggest that the degree of suture involvement may be
      related to early increases in ICP. Possible multifactorial explanations for
      intracranial decompression and compensation in the craniosynostotic rabbit model
      are discussed.

PMID- 10912717
TI  - Facial growth in adulthood after primary periosteoplasty or primary bone grafting
      in UCLP.
AB  - OBJECTIVE: The primary research aim of this study was to compare long-term
      differences in craniofacial morphology at adulthood between two groups of
      unilateral cleft lip and palate (UCLP) patients: one operated by primary
      periosteoplasty and the other by primary bone grafting. DESIGN: The two groups
      were followed longitudinally at 5-year intervals; this study examined the 15- to
      20-year age range. SETTING: University hospital/center located in Prague,
      Bohemia, Czech Republic. PATIENTS: 17 men with primary bone grafting, 29 men with
      primary periosteoplasty. INTERVENTIONS: Primary bone grafting or periosteoplasty.
      METHODS: Serial cephalometric radiographs. MAIN OUTCOME MEASURES: Conventional
      cephalometric and finite element measures. RESULTS: The mandibular symphysis was
      larger in the bone-grafted group. The periosteoplasty group displayed a more
      horizontal growth of the mandible with less rotation than the bone-grafted group.
      There were no other significant differences. CONCLUSIONS: We conclude that the
      original outcomes differences observed in childhood and adolescence were masked
      by skeletal and dental compensations in adulthood. These observations can be
      attributed to both natural growth and clinical intervention.

PMID- 10912718
TI  - Vascular endothelial growth pattern of endochondral bone graft in the presence of
      demineralized intramembranous bone matrix--quantitative analysis.
AB  - OBJECTIVE: To determine the timely ingrowth of new blood vessels of composite
      endochondral (EC) bone and demineralized bone matrix (DBM) prepared from
      intramembranous (IM) origin (EC-DBM(IM)) and to compare it with EC bone graft
      alone. DESIGN: Thirty-two rabbits with 32 critical-size (10 x 5 mm), full
      thickness bony defects in rabbit parietal bone were divided into two groups:
      composite EC-DBM(IM) group-implanted with composite autogenous EC bone and
      DBM(IM); EC bone group-implanted with EC bone alone. Two rabbits from each group
      were sacrificed-1, 2, 3, 4, 5, 6, 7, and 14 days after grafting.
      Neovascularization was assessed by immunohistochemical staining with antihuman
      angiogenesis-related endothelial cell antibodies (EN 7/44). Quantitative analysis
      of neovascularization, represented by percentage area of positive
      immunohistochemical staining, was performed on 320 sections of the experimental
      groups by a computer-assisted image analyzer. RESULTS: Positive
      immunohistochemical staining was first identified on day 2 post grafting for the
      composite EC-DBM(IM) group in comparison with day 4 in the EC bone graft group.
      The composite EC-DBM(IM) bone graft group showed earlier and almost 100% more
      neovascularization when compared with the EC bone graft group. CONCLUSION:
      DBM(IM) enhances healing and integration of EC bone graft by enhancing
      vascularization as well as increasing the amount of new blood vessels formed. In
      clinical cases in which EC autogenous bone is used to graft a large defect such
      as in cleft palate and craniofacial surgery, DBM(IM) should allow better
      integration and healing of the EC bone graft to the host bone.

PMID- 10912719
TI  - An investigation of the dentition of parents of children with cleft lip and
      palate.
AB  - OBJECTIVE: The aim of this investigation was to identify whether any dental
      features in parents of children with cleft lip and palate can be useful as
      predictors of clefting. METHODS: The dentition of 28 pairs of parents of children
      with complete unilateral (17) and bilateral (11) cleft lip and palate and 21
      pairs of parents of noncleft children were evaluated. Clinical and radiographic
      examinations were carried out to identify abnormalities of tooth number and
      morphology. Study cast assessment was undertaken to evaluate incisor
      relationship, overjet, overbite, intercanine widths, and mesiodistal widths of
      individual teeth, and these data were subjected to statistical analysis. RESULTS:
      The prevalence of abnormalities of tooth number in parents of cleft children was
      similar to those reported elsewhere for general populations. In parents of
      children with unilateral clefts, there was no tooth-size asymmetry between teeth
      on the side corresponding to the child's cleft and noncleft sides, respectively.
      No differences were found in tooth widths and intercanine widths between parents
      of children with unilateral clefts and parents of children with bilateral clefts.
      The incisor relationship, overjet, overbite, and intercanine widths were found
      not to differ statistically between the parents of cleft children and parents of
      noncleft children. CONCLUSIONS: No predictors of clefting could be identified in
      the dentition of parents of children with cleft lip and palate.

PMID- 10912720
TI  - Evaluation of primary dentition in cleft lip and palate children with and without
      natal/neonatal teeth.
AB  - OBJECTIVE: Natal/neonatal teeth are very common in children with complete
      unilateral and bilateral cleft lip and palate. The extraction of these teeth is
      the usual treatment in the Hospital for Rehabilitation of Craniofacial Anomalies.
      The objective of this study was to verify whether these teeth could be of the
      normal complement or whether they were supernumerary. DESIGN: The primary
      dentition of children with cleft lip and palate with and without natal/neonatal
      teeth was compared at the Hospital for Rehabilitation of Craniofacial Anomalies.
      SUBJECTS: The sample consisted of 55 children with complete unilateral and
      bilateral cleft lip and palate with natal/neonatal teeth and 54 without. RESULTS:
      No positive association between these groups and missing lateral incisor or
      supernumerary or complete dentition was found. CONCLUSION: The extraction of the
      natal/neonatal teeth did not alter the final complement of primary teeth, and
      these teeth could be the lateral incisor or supernumerary.

PMID- 10912721
TI  - Double tongue, intraoral anomalies, and cleft palate--case reports and a
      discussion of developmental pathology.
AB  - OBJECTIVE: Isolated cleft palate is the most common presentation of the
      nonsyndromic cleft lip/palate combinations and is multifactorial in etiology. We
      report two cases of children with clefts of the secondary palate coexistent with
      double tongue and in either case mandibular epulis or superiorly displaced
      salivary gland. RESULTS AND DISCUSSION: In each case, the palatal cleft
      correlated anatomically with the intraoral space-occupying lesion. The ratio of
      tongue volume to intraoral volume during palatogenesis is discussed with
      reference to the pathogenesis of cleft palate. These clinical cases propose the
      model of a unifying sequence of developmental events whereby deformation of
      palatal shelf elevation results in secondary palatal clefting.

PMID- 10912722
TI  - A possible otological complication due to maxillary expansion in a cleft lip and
      palate patient.
AB  - OBJECTIVE: We present a possible negative side effect of a sudden onset of
      secretory otitis media in a 12-year-old boy with unilateral cleft lip and palate
      who underwent maxillary expansion. The secretory otitis media caused a temporary
      hearing loss developed during the activation of the expander appliance. The
      possible causes for this complication are discussed. CONCLUSIONS: Clinicians
      should be aware of the possible association between maxillary expansion and
      secretory otitis media.

PMID- 10912723
TI  - State of the art in oral and maxillofacial surgery: treatment of maxillary
      hypoplasia and anterior palatal and alveolar clefts.

PMID- 10912724
TI  - Citalopram for verbal agitation in patients with dementia.
AB  - Various behaviors can be associated with dementing disorders. Management of these
      behaviors is often challenging to caregivers and clinicians. Verbal agitation
      such as talking constantly, screaming, and repeating phrases and noises is one of
      the most frequently encountered behaviors in the long-term care setting. We
      report two cases in which verbal agitation favorably responded to citalopram, a
      selective serotonin reuptake inhibitor. We also discuss some other factors
      possibly associated with this response. Nonetheless, citalopram appears to be an
      added option in the treatment of verbal agitation in demented patients.

PMID- 10912725
TI  - Treatment of verbal agitation with a selective serotonin reuptake inhibitor.
AB  - The objective of this study was to examine the safety and efficacy of paroxetine
      as an alternative to neuroleptic medications for the treatment of verbal
      agitation in demented patients. An open case series design was used, and the
      setting included two nursing homes and an outpatient geriatric clinic.
      Participants were eight consecutive nursing home residents and seven community
      dwelling older adults diagnosed with dementia who exhibited verbal agitation in
      the form of repetitive questions or unwarranted request for attention. Patients
      received paroxetine orally in doses of 10 mg to 40 mg per day. The Cohen
      Mansfield Agitation Inventory (CMAI) was used to rate the frequency of verbal
      agitation. A baseline score was obtained before starting paroxetine. Six scores
      were then obtained at 2-week intervals over a period of 3 months. All patients
      had reduction (2-4 points per item) in the CMAI scores at the end of the first
      month of treatment with paroxetine. Scores were further reduced (up to 5 points
      per item, 67%-71% reduction from baseline) in five patients at the end of the
      third month of treatment. Most patients tolerated paroxetine well. In this
      report, the use of paroxetine was associated with reduction in verbal agitation.
      This finding supports the possibility that verbal agitation in demented patients
      could be a manifestation of underlying depression.

PMID- 10912727
TI  - Family history of dementia and current depression in nondemented community
      dwelling older adults.
AB  - Since it has been postulated that mood disturbance in nondemented older adults
      may represent a prodromal feature of dementia for a subgroup of patients, it
      would be expected that patients with these symptoms would evidence a greater
      prevalence of family history of dementia. In a sample of 3225 community-dwelling
      cognitively intact elderly recruited from a free memory-screening program, we
      found that current depression was more common in participants with a positive
      versus a negative family history of dementia in first-degree relatives (17%
      versus 11%; Fisher's Exact Test, P < .0001). This relationship remained
      significant after controlling for age, education, gender, ethnicity, and Folstein
      Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5,
      P < .001). The results suggest that symptoms of depression may herald the onset
      of an incipient dementia syndrome in a subset of geriatric patients.
      Alternatively, the results may be indicative of familial aggregation of dementia
      and depression.

PMID- 10912726
TI  - Atypical dementia and spastic paraplegia in a patient with primary lateral
      sclerosis and numerous necortical beta amyloid plaques: new disorder or
      Alzheimer's disease variant?
AB  - Primary lateral sclerosis (PLS) and hereditary spastic paraplegia (HSP) are
      clinically similar disorders in which progressive lower limb spasticity and
      corticospinal tract degeneration are characteristic. We report the occurrence of
      progressive spastic paraplegia and frontal systems dementia in a patient with
      postmortem features of PLS combined with moderate Alzheimer-like changes in
      neocortex and hippocampus. This combination of clinical and neuropathologic
      findings has not been described in PLS or HSP and varies from other cases in
      which spastic paraplegia, dementia, and Alzheimer neuropathology occurred
      concurrently. This 69-year-old woman developed spastic quadriplegia and dementia
      over 12 years. Left leg weakness progressed over 7 years to paraplegia, then
      quadriplegia by age 68. Sensory and cerebellar function were preserved and
      fasciculations were absent. Dementia characterized by concrete thinking,
      perseveration, and impaired executive function appeared in the seventh year and
      remained relatively stable until 6 months before death at age 69. Degeneration of
      the lateral corticospinal and dorsal spinocerebellar tracts confined to the
      spinal cord was evident at postmortem examination. Brain stem, midbrain, and
      cerebellum were normal. Numerous beta/A4 amyloid positive diffuse plaques (10
      15/200x field) were apparent in neocortex, and neurofibrillary tangles
      immunopositive for paired helical filament were detected in hippocampus. This
      case broadens the spectrum of disorders associated with Alzheimer neuropathologic
      changes. The relationship between PLS, HSP, and Alzheimer's disease requires
      further study.

PMID- 10912728
TI  - Depressive syndromes and functional disability in dementia.
AB  - The goals of this study were to assess (1) the prevalence of major and minor
      depression in Alzheimer's disease (AD), ischemic vascular dementia (IVD), and
      mixed dementia (AD/IVD); (2) demographic and clinical variables that may be
      associated with depression; and (3) the relationship between depression severity
      and the level of functional impairment and cognitive decline. Demographic
      variables, depression diagnoses, Mini-Mental State Examination scores, and
      Blessed Roth Dementia Rating Scale scores were compared in patients with AD (N =
      582), IVD (N = 48), and mixed dementia (N = 61) using analysis of variance and
      linear regression models. Data were collected using standardized rating
      instruments at the time of the patients' initial evaluations at the University
      dementia clinics. The results were that (1) depression was related to lower
      education, (2) major depression was more prevalent in IVD compared to probable
      AD, and (3) functional impairment was greater in patients with minor or major
      depression compared to patients without depression. Our data suggest that the
      level of functional disability in dementia may be related to severity of
      depression. Additional studies are needed to validate our results and examine the
      contribution of additional neurobiologic factors to the pathophysiology of
      depression in dementia.

PMID- 10912729
TI  - Age-group differences in treatment outcomes for male veterans with severe
      schizophrenia: a three-year longitudinal study.
AB  - Treatment outcomes in later-life schizophrenia are poorly understood and of
      serious concern for clinicians and mental health policy makers. Age-group
      differences were examined for 499 male veterans with severe schizophrenia
      enrolled in enhanced treatment programs at 12 Veterans Affairs hospitals.
      Participants were separated into three age groups (20-39 years, 40-59 years, 60
      years and above), with the following outcomes assessed at enrolment and 1 and 3
      years afterwards: psychiatric symptomatology, global functioning, impairment in
      Instrumental Activities of Daily Living (IADL), and hospital use. All three age
      groups experienced significant improvement in psychiatric symptoms over time. The
      oldest group fared worse than younger patients in terms of global functioning and
      generally required more inpatient services and assistance with IADL. Innovative
      programming is needed to meet the special needs of the growing population of
      older adults with schizophrenia.

PMID- 10912730
TI  - Dementia in rural primary care practices in Lake County, Oregon.
AB  - Procedures used in assessing patients with dementia in rural settings are little
      studied. Among all patients aged 65 years and older in the four primary care
      practices in Lake County, Oregon, dementia cases were identified from
      computerized office databases using preselected International Classification of
      Diseases, Ninth Edition, codes. A semi-structured chart review determined (1) a
      dementia diagnosis, (2) cognitive and functional domains assessed, and (3)
      diagnostic studies performed. Of 1540 available records, 30 had dementia.
      Nineteen of them met National Institute of Neurological and Communicative
      Diseases and Stroke-Alzheimer's Disease and Related Disorders Association
      criteria for Alzheimer's disease (AD). Cognitive impairment was documented in 73%
      of the 51 identified charts and all with AD. Laboratory studies were recorded in
      33% overall and in 42% with AD. Neuroimaging was documented in 18% overall and in
      16% with AD. The prevalence of documented dementia in these rural practices may
      be low, possibly because cases of mild dementia may not be labeled as such.
      Laboratory studies were performed in a minority of cases of dementia.

PMID- 10912731
TI  - The male menopause and mood: testosterone decline and depression in the aging
      male--is there a link?
AB  - The objective of this study was to review the literature on the hormonal changes
      that occur in aging males in order to determine if testosterone declines in
      relation to depressed mood and if testosterone might prove useful in treatment of
      depression. Pertinent articles were identified through a MEDLINE search from 1966
      to 1999 and by careful review of the bibliographies of articles most relevant to
      the topic. There is a moderate decline of total testosterone and more significant
      decline of bioavailable testosterone in aging males. Elderly males who are
      depressed appear to have the lowest testosterone levels. In eugonadal males,
      testosterone replacement does not have a significant effect on mood; in
      hypogonadal males, some studies show an effect whereas others do not. In several
      small studies of depressed hypogonadal males, testosterone was effective in
      alleviating depression. Major side effects of testosterone include increased
      hematocrit and potential effects on the prostate and lipid metabolism.
      Testosterone replacement as primary or adjuvant treatment of depression may prove
      useful in elderly, hypogonadal males who fail to respond to conventional
      antidepressants. Further studies are needed to confirm these initial impressions.

PMID- 10912732
TI  - Effect of EEG electrode density on dipole localization accuracy using two
      realistically shaped skull resistivity models.
AB  - The effect of number of EEG electrodes on the dipole localization was studied by
      comparing the results obtained using the 10-20 and 10-10 electrode systems. Two
      anatomically detailed models with resistivity values of 177.6 omega m and 67.0
      omega m for the skull were applied. Simulated potential values generated by
      current dipoles were applied to different combinations of the volume conductors
      and electrode systems. High and low resistivity models differed slightly in
      favour of the lower skull resistivity model when dipole localization was based on
      noiseless data. The localization errors were approximately three times larger
      using low resistivity model for generating the potentials, but applying high
      resistivity model for the inverse solution. The difference between the two
      electrode systems was minor in favour of the 10-10 electrode system when
      simulated, noiseless potentials were used. In the presence of noise the dipole
      localization algorithm operated more accurately using the denser electrode
      system. In conclusion, increasing the number of recording electrodes seems to
      improve the localization accuracy in the presence of noise. The absolute skull
      resistivity value also affects the accuracy, but using an incorrect value in
      modelling calculations seems to be the most serious source of error.

PMID- 10912733
TI  - Stability of late event-related potentials: topographical descriptors of motor
      control compared with the P300 amplitude.
AB  - The P300-amplitude evoked with an acoustic oddball-paradigm is considered the
      most stable late event-related potential (ERP). This amplitude-index has become a
      standard parameter in electrophysiology. Recently, a robust ERP-parameter (NoGo
      anteriorization, NGA) has been introduced, which reflects spatial brain
      electrical changes in relation to execution and inhibition of a motor response
      elicited with a Continuous Performance Test (CPT). The current study refers to
      the stability of this new topographical ERP-parameter compared to the stability
      of the classical P300-amplitude. For that purpose, 12 healthy subjects were
      investigated with both paradigms during recording of a 21-channel EEG. Analysis
      of the resulting ERPs revealed a very high stability for both, topographical and
      amplitude index: In every single subject, the brain electrical fields were
      characterized by a more anterior location in the NoGo- compared to the Go
      condition (=NGA) and by higher amplitudes after target compared to distractor
      condition. T-tests, analyses of the effect size and of the power revealed
      equivalent differences between the two contrasting conditions for the
      topographical compared to the amplitude index. These results indicate that the
      stability of the topographical ERP-parameters elicited with the CPT is sufficient
      for an electrophysiological standard-index. The possibility to elicit a robust
      and specific spatial brain activation with the CPT is an ideal completion to the
      classical P300 amplitude effect and, therefore, hopefully will be a useful
      expansion of the standard paradigms in electrophysiological laboratories.

PMID- 10912734
TI  - Trilinear modeling of event-related potentials.
AB  - This paper describes a method for estimating a set of spatial components (brain
      maps) and temporal components (waveforms) of brain potentials. These components
      play the role of bases of a coordinate system, in the sense that the brain
      potentials of any subject can be represented as superpositions of these
      components. The representation is unique given the spatial and temporal
      components, and this decomposition is particularly appealing for comparing the
      brain potentials of different subjects (say alcoholics and controls). It can also
      be used for single trial modeling, clinical classification of patients, and data
      filtering. The method is based on the topographic component model (TCM, Mocks
      1988) which models brain potentials in a trilinear form. We extend the TCM in two
      aspects. First, the diagonal amplitude matrix is replaced by a general loading
      matrix based on some neurophysiological considerations. Secondly, the number of
      spatial components and the number of temporal components can be different. The
      spatial components and temporal components are obtained respectively by
      performing singular value decomposition (SVD). This method is illustrated with
      visual P3 data.

PMID- 10912735
TI  - Localization of the epileptic focus by low-resolution electromagnetic tomography
      in patients with a lesion demonstrated by MRI.
AB  - Patients with medically intractable partial epilepsy and well-defined symptomatic
      MRI lesions were studied using phase-encoded frequency spectral analysis (PEFSA)
      combined with low-resolution electromagnetic tomography (LORETA). Ten patients
      admitted to the epilepsy monitoring unit with MRI-identified lesions and
      intractable partial epilepsy were studied using 31-electrode scalp EEG. The scalp
      electrodes were located in three-dimensional space using a magnetic digitizer and
      coregistered with the patient's MRI. PEFSA was used to obtain a phase-encoded
      scalp map for the ictal frequencies. The ictal generators were obtained from the
      scalp map using LORETA. In addition, the generators of interictal epileptogenic
      spikes were identified using time-domain LORETA. The LORETA generators were
      rostral to the MRI lesion in 87% (7/8) of patients with temporal lobe lesions,
      but all were located in the mesial temporal lobe in concordance with the
      patients' MRI lesions. In patients with frontal lobe epilepsy, the ictal
      generators at the time that the spectral power was maximal localized to the MRI
      lesions. Eight of 10 patients had interictal spikes, of which 4 were bilateral
      independent temporal lobe spikes. Only generators of the interictal spikes that
      were ipsilateral to seizure onset correlated with the ictal generators. LORETA
      combined with PEFSA of the ictal discharge can localize ictal EEG discharges
      accurately and improve correlation with brain anatomy by allowing coregistration
      of the ictal generator with the MRI. Analysis of interictal spikes was less
      useful than analysis of the ictal discharge.

PMID- 10912736
TI  - Moving mesh method for reconstructing some spread sources in the brain.
AB  - The purpose of this paper is to propose a new algorithm for the analysis of
      biomagnetic field data obtained from magnetoencephalography (MEG) measurements.
      This new method overcomes two major problems faced by the current method of data
      analysis. The first problem is the need to determine the number of sites of brain
      activity before calculations can be performed. The second problem is inability of
      the analysis to provide any information regarding the volume of the brain
      activity. The new data analysis method, called the Moving Mesh Method (MMM), is
      capable of analyzing MEG data without the need to determine the number of sources
      beforehand. In addition, the MMM determines the location of brain activity as a
      three dimensional volume, instead of as a point source of activity. The MMM uses
      an iterative method of calculating the position of the sources to achieve greater
      accuracy, and a regularized g-inverse matrix to stabilize its solution. The
      feasibility of the MMM was examined by two methods. First, a computer simulation
      was used to confirm the MMM's capability to analyzing MEG data. In the second
      experiment, the MMM was applied to analyze somatosensory evoked fields obtained
      using a new imaging system (Shimadzu Biomagnetic Imaging System, Model-100). From
      the interpretation of the results, we have concluded that the MMM is a feasible
      method of biomagnetic data analysis.

PMID- 10912738
TI  - Plasma endothelin is increased in early essential hypertension.
AB  - Local vascular generation of endothelin-1 (ET-1) may contribute to elevated
      peripheral resistance in hypertension. We tested the hypothesis that
      immunoreactive ET production in the forearm circulation is increased in early
      essential hypertensive subjects. Ten young, previously untreated male patients
      with mild essential hypertension and no signs of target organ damage were
      compared with matched normotensive subjects in an outpatient setting. Arterial
      and venous samples were obtained from indwelling catheters in the brachial artery
      and the medial cubital vein, respectively. Samples were collected at baseline and
      after induction of endothelium-dependent (acetylcholine) vasodilation.
      Immunoreactive ET (ET) was measured after column extraction by a sensitive
      radioimmunoassay employing a C-terminal ET-1 antibody with negligible cross
      reaction to big-ET. Individual recovery rates were determined for each sample.
      Basal ET was significantly higher in hypertensive than in normotensive subjects,
      both in venous and arterial samples (P < .01). This difference was also present
      after correction for recovery (P < .01). There was no significant difference
      between venous and arterial ET concentrations. Local vasodilation did not change
      arterial or venous ET levels. In conclusion, plasma ET is increased in young,
      untreated, essential hypertensive subjects with no signs of target organ damage.
      The increased circulating immunoreactive ET may point to a role for the peptide
      early in the development of high blood pressure.

PMID- 10912737
TI  - Orthostatic hypotension and the incidence of coronary heart disease: the
      Atherosclerosis Risk in Communities study.
AB  - We examined the association between orthostatic hypotension (OH) at baseline
      examination (1987-1989) and the incidence of coronary heart disease (CHD) over an
      average of 6 years, among 12,433 black and white middle-aged men and women
      participating in the Atherosclerosis Risk in Communities (ARIC) study. OH was
      defined as a SBP decrease > or = 20 mm Hg or a DBP decrease > or = 10 mm Hg after
      changing from supine to standing. CHD events included definite or probable
      myocardial infarctions (MI), silent MI, and fatal CHD. Five percent of
      participants had OH. Prevalence increased with advancing age and was more common
      among those with cardiovascular disease (CVD)-related comorbidities and risk
      factors. Those with OH had an increased risk of CHD (hazard ratio [HR] = 3.49,
      95% confidence interval [CI] = 2.58, 4.73). This association was attenuated after
      controlling for age, ethnicity, gender, comorbid conditions, and CVD risk factors
      (HR = 1.85, 95% CI = 1.31, 2.63).

PMID- 10912739
TI  - Association between muscle fiber composition and blood pressure levels during
      exercise in men.
AB  - Normotensive individuals with a magnified blood pressure (BP) level during
      exercise have an increased risk for developing hypertension. The purpose of this
      study was to determine if skeletal muscle fiber type is related to the BP level
      during exercise. Peak BP was determined in 35 normotensive, middle-aged (mean +/-
      SE, 46.0 +/- 1.8 years) men during maximal treadmill exercise. Fiber distribution
      (I, IIa, IIb) was measured in muscle samples (percutaneous needle biopsy) from
      the vastus lateralis and lateral gastrocnemius. The systolic BP during exercise
      was significantly (P < .05) related to the percentage of type IIb fibers in both
      the vastus lateralis (r = 0.37) and gastrocnemius (r = 0.38). Mean arterial
      pressure BP was also related to the percentage of type IIb fibers in the
      gastrocnemius (r = 0.39, P < .05), with a similar trend evident in the vastus
      lateralis (r = 0.31, P = 0.08). The percentage of type IIb muscle fibers in both
      muscle groups was associated with (P < .05) body fat (vastus lateralis, r = 0.44;
      gastrocnemius, r = 0.43). There were no relationships between the relative
      percentage of type I or IIa fibers with any BP parameters. Maximal oxygen
      consumption was negatively related to BP, but only when expressed relative to
      body weight (mL x kg(-1) x min(-1)). These data suggest that muscle morphology is
      related to the blood pressure level during exercise and provides insight into
      factors that may predispose individuals toward the development of hypertension
      and cardiovascular disease.

PMID- 10912740
TI  - Aerobic exercise training fails to reduce blood pressure in nondipper-type
      hypertension.
AB  - To assess whether aerobic exercise training is an effective and an alternative
      method to control blood pressure (BP) in hypertension, 32 uncomplicated, never
      treated patients suffering from mild-to-moderate essential arterial hypertension
      (EAH) were included in an aerobic exercise training program using a regular
      standardized cycle ergometer exercise for 3 months. In all EAH patients, before
      and after the exercise training period, ambulatory BP monitoring (ABPM) was
      performed and several metabolic variables were assessed. Before exercise, in 20
      EAH patients, a 48-h ABPM showed a normal day-night rhythm, with nocturnal BP
      decrease, according to a dipper-type hypertension, whereas in 12 EAH patients 48
      h ABPM profile indicated a nondipper-type hypertension. After exercise, EAH
      dippers presented a significant decrease in the daytime systolic and diastolic
      BP, whereas EAH nondippers did not show any change in daytime and nighttime
      systolic and diastolic BP. Our study confirms the controversy about the
      postulated BP lowering effect of dynamic exercise in EAH patients, in the sense
      that only EAH dipper patients seem to obtain a beneficial diurnal lowering BP
      effect deriving from exercise, possibly through a reduction in sympathetic tone.
      On the contrary, physical activity seems to fail in reducing diurnal and
      nocturnal BP values in EAH nondippers, suggesting that in nondipper-type
      hypertension, other "masking" endogenous or exogenous factors could interfere
      with and prevail over the adrenergic-vagal balance that modulates the day-night
      BP synchronism.

PMID- 10912741
TI  - Nocturnal blood pressure dipping: a consequence of diurnal physical activity
      blipping?
AB  - This study was designed to describe the interaction between physical activity
      (PA), quantified objectively by electronic activity monitors, and ambulatory
      blood pressure (ABP), and to test the hypothesis that modifying daily PA can
      effect significant changes in the diurnal variation in blood pressure and may
      result in altered dipping/nondipping status of an individual. Initially, 70
      individuals underwent simultaneous ABP and electronic activity monitoring
      (actigraph devices manufactured by Gaewihler Electronics, Switzerland) over a 24
      h period. Then, in a prospective study, the dipping/nondipping status of 43
      subjects was assessed using ABP recorded over two 24-h periods of differing
      activity levels. Of the 70 subjects (age 49 +/- 11 years, 42 male) the diurnal
      variation in systolic blood pressure (20 +/- 12%, step-up from night [120 +/- 12
      mm Hg] to day [144 +/- 13 mm Hg]) and diurnal variation in PA score (increment
      from sleep, 44 +/- 17 units) correlated significantly (R2 = 0.29; P < .05). Of
      the 43 subjects who underwent ABP monitoring on a more active day, four had a
      nondipping BP profile; 12 of these same 43 subjects had a nondipping BP profile
      when monitored on a less active day (chi2 = 4.9; P < .05). These results provide
      a quantitative description of the contribution of PA, including the sleep/awake
      status, to blood pressure variation in a group of normotensive and hypertensive
      individuals. The magnitude of this effect underscores the importance of
      interpreting 24-h ABP data only in the presence of adequately quantified activity
      data.

PMID- 10912742
TI  - The use of antihypertensive therapy in Spain (1986-1994).
AB  - We aimed to analyze the trends in antihypertensive therapy in Spain during the
      period 1986 to 1994, as well as the change in the pattern of different drugs, in
      relation to different national/international recommendations for hypertension
      treatment. Antihypertensive consumption was studied using the defined daily dose
      (DDD) and the DHD (DDD/1000 inhabitants/day) of each drug, as defined by the Drug
      Utilization Research Group of the European Office of the World Health
      Organization. The anatomical classification of hypotensive drugs has been made
      according to EPhMRA (European Pharmaceutical Market Association) guidelines. A
      significant increase of 117.4% (41.39/90 DHD) in antihypertensive drug
      consumption was observed in the period 1986 to 1994. In 1986 diuretics were the
      most consumed (30.27 DHD), followed by calcium antagonists (5.37), beta-blockers
      (3.93), and the angiotensin-converting enzyme (ACE) inhibitor (1.37). In 1994 ACE
      inhibitors, calcium antagonists, and beta-blockers increased significantly (P <
      .0001), whereas diuretics were still the most commonly prescribed. Nifedipine and
      captopril were the most used among calcium antagonists and ACE inhibitors.
      National and international recommendations had no effect on prescription
      patterns. Antihypertensive therapy of all types is increasing in Spain. Diuretics
      remain the most popular, beta-blockers stay stable, whereas the newer types are
      rising rapidly. National and international recommendations had no effect on
      prescription patterns.

PMID- 10912743
TI  - Effects of low-dose aspirin on clinic and ambulatory blood pressure in treated
      hypertensive patients. Collaborative Group of the Primary Prevention Project
      (PPP)--Hypertension study.
AB  - Nonsteroidal antiinflammatory drugs may affect blood pressure (BP) control in
      hypertensive patients receiving drug treatment, but data on the effects of low
      dose aspirin are scanty. This study assessed the effects of chronic treatment
      with low doses of aspirin (100 mg/day) on clinic and ambulatory systolic (SBP)
      and diastolic (DBP) BP in hypertensives on chronic, stable antihypertensive
      therapy. The study was conducted in the framework of the Primary Prevention
      Project (PPP), a randomized, controlled factorial trial on the preventive effect
      of aspirin or vitamin E in people with one or more cardiovascular risk factors.
      Fifteen Italian hypertension units studied 142 hypertensive patients (76 men, 66
      women; mean age 59 +/- 5.9 years) treated with different antihypertensive drugs:
      71 patients were randomized to aspirin and 71 served as controls. All patients
      underwent a clinic BP evaluation with an automatic sphygmomanometer and a 24-h
      ambulatory BP monitoring, at baseline and after 3 months of aspirin treatment. At
      the end of the study the changes in clinic SBP and DBP were not statistically
      different in treated and untreated subjects. Ambulatory SBP and DBP after 3
      months of aspirin treatment were similar to baseline: deltaSBP -0.5 mmHg (95%
      confidence intervals [CI] from -1.9 to +2.9 mm Hg) and deltaDBP -1.1 mm Hg (95%
      CI from -2.5 to +0.3 mm Hg). The pattern was similar in the control group. No
      interaction was found between aspirin and the most used antihypertensive drug
      classes (angiotensin converting enzyme inhibitors and calcium antagonists).
      Despite the relatively small sample size our results seem to exclude any
      significant influence of low-dose aspirin on BP control in hypertensives under
      treatment.

PMID- 10912744
TI  - Hyperapobetalipoproteinemia with compositional abnormality of LDL and IDL, a
      characteristic lipoprotein alteration in essential hypertension.
AB  - The number and composition of apoprotein B (apoB)-containing lipoproteins that
      are very low density lipoprotein (VLDL), intermediate-density lipoprotein (IDL),
      and low-density lipoprotein (LDL) have been analyzed in subjects with essential
      hypertension who have no obesity and glucose intolerance. Twenty-three essential
      hypertensive subjects without diabetes mellitus and obesity were recruited. VLDL,
      IDL, LDL, and high-density lipoprotein (HDL) were separated by
      ultracentrifugation in the 23 hypertensive and 17 healthy subjects (control
      group). ApoB was determined by highly sensitive latex agglutination method in
      each lipoprotein fraction. There were no significant differences in age and body
      mass index between the hypertension and control groups. In hypertension,
      cholesterol levels significantly increased in plasma (13%, P < .05) and in LDL
      (20%, P < .05), but decreased in HDL (-14%, P < .05). Triglyceride significantly
      increased in plasma (66%, P < .05) and in VLDL (105%, P < .05). ApoB also
      significantly increased in plasma and all lipoprotein fractions except HDL.
      (plasma, 35%; VLDL, 94%; IDL, 82%; LDL, 42%; P < .05). With respect to
      lipoprotein composition, the ratio of cholesterol to apoB significantly decreased
      in IDL (P < .05) and LDL (P < .05). In essential hypertension, the number of apoB
      containing lipoproteins (VLDL, IDL, LDL) all increased. A low ratio of
      cholesterol to apoB without changes in the ratio of triglyceride to apoB was
      noted in IDL and LDL, indicating the presence of small dense lipoprotein
      particles. Characteristic disorders of pure essential hypertension are
      characterized by hyperapobetalipoproteinemia and small dense LDL.

PMID- 10912745
TI  - Home blood pressure: accuracy is independent of monitoring schedules.
AB  - Long-term morbidity and mortality from hypertension are more closely related to
      home than to casual office blood pressure levels. There is no generally accepted
      recommendation on how to best schedule home blood pressure (HBP) recordings,
      perhaps because the effect of varying the home monitoring schedule on the HBP
      average is not well studied. The goals of this analysis are to describe the
      effects of HBP monitoring schedules on the accuracy of resultant HBP averages and
      to determine which monitoring schedule parameters correlate with HBP accuracy.
      Twelve published studies, each including home, office, and awake ambulatory blood
      pressure means were identified. Accuracy of office and HBP averages were
      determined by their agreement with corresponding awake ambulatory averages.
      Variations in HBP monitoring schedule parameters did not significantly affect the
      accuracy of the resultant HBP averages among the studies. In univariate analyses,
      no individual parameter correlated significantly with the final HBP average
      accuracy. As the total number of HBP readings obtained increased, or as other
      monitoring schedule parameters intensified, the superior accuracy of HBP levels
      as compared to that of casual office values also failed to significantly improve.
      No HBP accuracy differences were found among groups characterized by different
      HBP schedule parameter ranges. In conclusion, the accuracy of HBP measurements,
      as determined by their agreement with an awake ambulatory mean, is maintained
      regardless of substantial variations in HBP monitoring schedules. Therefore, the
      majority of the benefits derived from HBP monitoring will likely be achieved by
      obtaining only a few HBP measurements using a minimally complex monitoring
      schedule.

PMID- 10912746
TI  - Comparison of three blood pressure measurement methods for the evaluation of two
      antihypertensive drugs: feasibility, agreement, and reproducibility of blood
      pressure response.
AB  - Our objective was to compare three different methods of blood pressure
      measurement through the results of a controlled study aimed at comparing the
      antihypertensive effects of trandolapril and losartan. Two hundred and twenty
      nine hypertensive patients were randomized in a double-blind parallel group
      study. After a 3-week placebo period, they received either 2 mg trandolapril or
      50 mg losartan once daily for 6 weeks. At the end of both placebo and active
      treatment periods, three methods of blood pressure measurement were used: a)
      office blood pressure (three consecutive measurements); b) home self blood
      pressure measurements (SBPM), consisting of three consecutive measurements
      performed at home in the morning and in the evening for 7 consecutive days; and
      c) ambulatory blood pressure measurements (ABPM), 24-h BP recordings with three
      measurements per hour. Of the 229 patients, 199 (87%) performed at least 12 valid
      SBPM measurements during both placebo and treatment periods, whereas only 160
      (70%) performed good quality 24-h ABPM recordings during both periods (P <
      .0001). One hundred-forty patients performed the three methods of measurement
      well. At baseline and with treatment, agreement between office measurements and
      ABPM or SBPM was weak. Conversely, there was a good agreement between ABPM and
      SBPM. The mean difference (SBP/DBP) between ABPM and SBPM was 4.6 +/- 10.4/3.5 +/
      7.1 at baseline and 3.5 +/- 10.0/4.0 +/- 7.0 at the end of the treatment period.
      The correlation between SBPM and ABPM expressed by the r coefficient and the P
      values were the following: at baseline 0.79/0.70 (< 0.001/< .0001), with active
      treatment 0.74/0.69 (0.0001/.0001). Hourly and 24-h reproducibility of blood
      pressure response was quantified by the standard deviation of BP response.
      Compared with office blood pressure, both global and hourly SBPM responses
      exhibited a lower standard deviation. Hourly reproducibility of SBPM response
      (10.8 mm Hg/6.9 mm Hg) was lower than hourly reproducibility of ABPM response
      (15.6 mm Hg/11.9 mm Hg). In conclusion, SBPM was easier to perform than ABPM.
      There was a good agreement between these two methods whereas concordance between
      SBPM or ABPM and office measurements was weak. As hourly reproducibility of SBPM
      response is better than reproducibility of both hourly ABPM and office BP
      response, SBPM seems to be the most appropriate method for evaluating residual
      antihypertensive effect.

PMID- 10912747
TI  - Does hypertension and its pharmacotherapy affect the quality of sexual function
      in women?
AB  - Considerable research has been conducted into the effects of antihypertensive
      drugs on male sexual functioning. This remains underexplored in women, even
      though almost half of treated hypertensives are women. An ambulatory medical
      record-based, case-control study was designed to study sexual function in treated
      and untreated hypertensive women and healthy controls. We conducted this study at
      a teaching hospital with satellite clinics in upstate New York. Of 3312 medical
      records reviewed, 640 premenopausal white women with or without mild hypertension
      (defined as blood pressure [BP] > or = 140/90 and < 160/110 mmHg), in
      heterosexual relationships, with no other significant medical history, were
      eligible. Of these, 241 women agreed to participate, and 224 (35%) completed both
      a self-administered questionnaire and a telephone interview. Analysis was
      conducted on 211 women (107 healthy controls, and 104 mild hypertensives, of whom
      37 were unmedicated and 67 medicated). Questions on sexuality were classified
      into seven composite variables and later further divided. There were no
      demographic differences between participants and nonparticipants. Cases and
      controls differed only by age (P < .01); therefore, subsequent analysis was age
      adjusted. Current smokers reported a significantly lower mean score for orgasm
      than did nonsmokers (P = .04). Women with unmedicated and medicated hypertension
      did not differ significantly on sexuality scores and were subsequently combined.
      Using age-adjusted ANOVA, women with hypertension reported significantly
      decreased lubrication and orgasm and increased pain compared to nonhypertensive
      women. There were no significant differences by ANOVA in the quality of sexual
      functioning between six treatment groups. In conclusion, the quality of female
      sexual functioning was quantified in an ambulatory outpatient setting.
      Hypertensive women, regardless of type of treatment, reported age-adjusted
      decrease in vaginal lubrication, less frequent orgasm, and more frequent pain
      when compared to nonhypertensive women. Emotional aspects of sexual functioning
      in hypertensive women do not appear to be impaired. These areas require further
      investigation. An incidental finding indicated diminished orgasm reported in
      current smokers, compared to nonsmokers, which was not associated with age or
      hypertension.

PMID- 10912748
TI  - Genetic variation of the gamma subunit of the epithelial Na+ channel and
      essential hypertension. Relationship with salt sensitivity.
AB  - We evaluated the association of a common polymorphism in gammaENaC, consisting in
      a C to G transversion in codon 649, with essential hypertension and to the
      pressor response to salt in whites. Two hundred fifteen essential hypertensive
      patients, and 137 normotensive controls were genotyped for the gamma649 ENaC
      polymorphism by polymerase chain reaction method and diagnostic restriction
      enzyme digestion. The genotype distribution of the gamma649 ENaC polymorphism in
      the hypertensives, 129 CC (60%) and 86 CG/GG (40%) was not significantly
      different from that of the control group, 84 CC (61%) and 53 CG/GG (39%) (P =
      .81). Salt sensitivity was assessed in a group of 48 patients by 24-h mean blood
      pressure response to changes in salt intake. Nineteen patients were diagnosed as
      salt sensitive, whereas 29 had salt-resistant hypertension. The gamma649 ENaC
      genotype distribution in salt-sensitive patients was 12 CC (63%) and 7 CG/GG
      (37%), not significantly different from the distribution in the salt-resistant
      group, 19 CC (65%) and 10 CG/GG (35%), P = .87. The changes in systolic,
      diastolic, and mean blood pressure as measured by ambulatory blood pressure
      monitoring, and in plasma renin activity and plasma aldosterone induced by high
      salt diet were not different among the gamma649 ENaC genotypes. In the present
      study we found no association between the gamma649 ENaC polymorphism and
      essential hypertension or salt sensitivity. Although these data do not support a
      major causative role for this polymorphism, we cannot exclude that a functional
      mutation elsewhere in ENaC might be associated with essential hypertension.

PMID- 10912749
TI  - Molecular variations in the calcium-sensing receptor in relation to sodium
      balance and presence of hypertension in blacks and whites.
AB  - Sodium (Na) excretion is to an extent tied to calcium (Ca) excretion; increases
      in Ca result in increased Na excretion. We hypothesized that molecular variation
      in the calcium-sensing receptor (CaSR), which imparts certain of the influences
      of extracellular Ca, might be related to differences in Na balance and blood
      pressure. We further hypothesized that such an influence by CaSR is more
      pronounced in blacks than in whites, as the hypertension in blacks appears to be
      more dependent on Na retention. Three common molecular variants in CaSR were
      studied. Two were more frequent in the whites (A986S, P < .0001, and G990R, P =
      .093), whereas Q1011E was more frequent in the blacks (P < .0001). Two distinctly
      separate groups were studied: (1) healthy schoolchildren in whom levels of the
      renin-aldosterone axis and blood pressure were measured, and (2) normotensive and
      hypertensive adults. Studies of association were made separately in the whites
      and the blacks. No association of any of the variants with Na balance (as
      estimated from renin and aldosterone levels) was observed. In the black
      schoolchildren, Q1011E showed a marginal association with a higher blood pressure
      (P = .093 for systolic and P = .025 for diastolic), a relationship that was
      considered to be nonsignificant after adjusting for multiple comparisons. Nor was
      there a significant association of the variants with presence or absence of
      hypertension. In summary, studies of two cohorts that included whites and blacks
      did not suggest that molecular variations in the CaSR influence either Na balance
      or blood pressure.

PMID- 10912750
TI  - Hypertension and insulin resistant models have divergent propensities to learned
      helpless behavior in rodents.
AB  - The induction of learned helpless (LH) behavior in rats is a widely used model of
      unipolar depression. Recent studies have linked depression with hypertension and
      insulin resistance as observed in obesity, but the propensity of these disorders
      to manifest depression has not been reported. In this study, the LH behavioral
      paradigm was exploited in a model of hypertension (Dahl rat) and of insulin
      resistance (Zucker rat) to determine the propensity of these models to develop
      depression and to examine the profile of markers for the propensity of the
      cardiovascular system (plasma renin activity) and of the hypothalamus-pituitary
      adrenal axis (corticosterone) in the display of propensity to depression. Results
      show that Zucker rats displayed the lowest propensity to the development of LH
      behavior (12%), followed by the control Sprague-Dawley rats (27%), and then Dahl
      rats (66%). In contrast, congenital learned helpless (cLH) rats, a genetically
      bred strain for animal depression, had the highest propensity (>90%). A gender
      effect was observed in the Zucker and cLH rats, with females showing an increased
      propensity to develop LH behavior. Plasma renin activity in the Dahl and Sprague
      Dawley rats after the LH stress paradigm was not significantly different from
      baseline. In contrast, Zucker rats, with the lowest propensity to LH behavior,
      demonstrated a threefold increase in plasma renin activity after stress.
      Congenital LH rats, with the highest propensity to LH behavior, exhibited a
      significantly lower increase (43%) in plasma renin activity after stress.
      Hyporesponsive hypothalamus-pituitary-adrenal (HPA) axis functioning correlated
      with propensity of LH behavior. Stress-induced corticosterone levels increased
      under twofold in cLH rats, whereas they increased more than sevenfold in Zucker
      rats. Taken together, these studies suggest that whereas genetically prone
      hypertensive rats have a very high propensity to depression, insulin-resistant
      rats have a profound resistance to depression. Moreover, a hyporesponsive HPA
      axis may be a marker for disorders that are comorbid with depression, whereas a
      hyperresponsive renin-angiotensin system may be indicative of resilience.

PMID- 10912751
TI  - Potassium augments vascular relaxation mediated by nitric oxide in the carotid
      arteries of hypertensive Dahl rats.
AB  - The present study was designed to determine whether and how potassium
      supplementation improves the endothelial function of carotid arteries of
      hypertensive Dahl rats. Dahl salt-sensitive rats were fed a high sodium diet, a
      high sodium plus potassium-supplemented diet, a normal rat chow, or a potassium
      supplemented diet for 4 weeks. High sodium intake significantly increased the
      blood pressure, which was attenuated by potassium supplementation. The isometric
      tension of rat-isolated carotid rings was measured. In norepinephrine
      precontracted rings, the relaxation in response to acetylcholine, adenosine 5'
      diphosphate (ADP), and isoproterenol were significantly attenuated in
      hypertensive Dahl rats, which was improved by potassium supplementation.
      Pretreatment with N(G)-nitro-L-arginine methyl ester blocked the responses to
      acetylcholine and ADP, and eliminated the difference in relaxation in response to
      isoproterenol. The endothelium-independent relaxation in response to forskolin, S
      nitroso-N-acetyl-DL-penicillamine, and sodium nitroprusside was significantly
      attenuated in hypertensive Dahl rats, which was not affected by potassium
      supplementation. The results indicated that salt-induced hypertension was
      associated with marked alterations in the endothelial and vascular smooth muscle
      functions of the carotid arteries of Dahl rats. Potassium supplementation
      ameliorated the endothelial but not the smooth muscle function. The protective
      effect of potassium appeared to be achieved through increased endothelial nitric
      oxide production. The current studies, in conjunction with our recent studies on
      nitric oxide synthase activity in the kidney, strongly suggest that potassium
      attenuates development of hypertension by increasing nitric oxide production in
      Dahl rats.

PMID- 10912753
TI  - Home blood pressure normalcy: the Didima study.
AB  - To evaluate reference values of home blood pressure (HBP) a cross-sectional
      community study was conducted on 694 adult subjects (aged > or = 18 years) of the
      village Didima in southern Greece (participation rate 76.4%). Clinic blood
      pressure (CBP) was measured on two visits (triplicate measurements, mercury
      sphygmomanometer) and HBP on 3 workdays (duplicate morning and evening
      measurements, oscillometric devices; Omron HEM 705CP). After exclusion of 132
      subjects (103 treated hypertensives and 29 with incomplete data), 562 subjects
      were analyzed (mean +/- SD aged 51.2 +/- 17.2 years, 42.7% men). Average HBP
      (120.0 +/- 17.8/72.6 +/- 8.8 mm Hg, systolic/diastolic) was strongly correlated
      (P < .0001) with CBP (118.7 +/- 17.7/73.8 +/- 10.5 mm Hg). Systolic CBP was 1.3
      mm Hg lower than HBP (P < .01, 95% confidence interval 0.4, 2.2), whereas
      diastolic CBP was 1.2 mm Hg higher than HBP (P < .0001, 95% confidence interval
      0.6, 1.7). The threshold of HBP normality determined using three different
      approaches was 1) 139.7/83.0 mm Hg (systolic/diastolic) using the distribution
      criterion (95th percentile of the HBP distribution among 476 normotensive
      subjects); 2) 139.7/85.8 mm Hg using the correspondence criterion (the
      percentiles of the CBP distribution that correspond to CBP > or = 140/90 mm Hg
      were estimated, and the levels of BP that correspond to these same percentiles on
      the HBP distribution were calculated); and 3) 137.4/82.7 mm Hg using the
      regression criterion (calculation of the levels of HBP that correspond to CBP of
      140/90 mm Hg using the regression equation between HBP and CBP). Overall, the
      findings of the three criteria suggest that average HBP < 137/82 mm Hg might be
      considered as probably normal, > 140/86 mm Hg as probably abnormal, and within
      these limits as borderline. Until mortality-based prospective data are available,
      this approach might be useful in the interpretation of HBP in clinical practice.

PMID- 10912752
TI  - Type 1A dopamine receptor expression in the heart is not altered in spontaneously
      hypertensive rats.
AB  - We have recently demonstrated that type 1A dopamine (D1A) receptor is expressed
      in the rat heart, but its function still remains unknown. In the present study,
      we investigated possible changes in the expression level and the distribution of
      the cardiac D1A receptor in the development of left ventricular hypertrophy in
      spontaneously hypertensive rats/Izumo strain (SHR/Izm) at the ages of 4, 8, and
      20 weeks. We examined D1A receptor protein distribution by immunohistochemistry
      and gene expression by competitive polymerase chain reaction (competitive PCR).
      In SHR/Izm, compared with the age-matched Wistar Kyoto rats/Izmo strain
      (WKY/Izm), blood pressure and heart/body weight ratio were significantly
      increased at 8 and 20 weeks. By immunohistochemistry, the D1A receptor was
      localized in cardiomyocytes and vascular smooth muscle cells of coronary
      arteries, but not in interstitial fibrotic tissue. D1A receptor distribution was
      not changed either by the strain or the age. Competitive PCR analysis showed that
      the D1A receptor mRNA level was significantly higher at 4 weeks than at 8 and 20
      weeks in both strains of rats and that there was no significant difference in D1A
      receptor mRNA between SHR/Izm and WKY/Izm at any age (43.2 +/- 10.4 attomol x 10(
      3)/L v 43.1 +/- 11.2 attomol x 10(-3)/L at 4 weeks, P = not significant, 3.9 +/-
      0.9 attomol x 10(-3)/L v 4.0 +/- 1.3 attomol x 10(-3)/L at 8 weeks, P = not
      significant, 3.0 +/- 1.2 attomol x 10(-3)/L v 1.9 +/- 1.6 attomol x 10(-3)/L at
      20 weeks, P = not significant). These results do not support the hypothesis that
      changes in D1A receptor expression are associated with the development of left
      ventricular hypertrophy in SHR.

PMID- 10912754
TI  - Morphological changes in cavernous tissue in spontaneously hypertensive rats.
AB  - Erectile dysfunction has an increased prevalence in hypertensive patients and is
      associated with cardiovascular diseases. For many years the discussion has been
      polarized on whether in hypertensive patients, it is the arterial hypertension or
      the antihypertensive therapy that is the cause of male erectile dysfunction. The
      aim of our study was to determine the morphologic changes in cavernous tissue
      (CT) in an animal model of arterial hypertension. Male spontaneously hypertensive
      rats (SHR) (n = 15) and normotensive Wistar-Kyoto (WKY) rats (n = 15) were
      studied for 8 months. Animals were allowed to drink tap water and fed a standard
      rat chow ad libitum. Systolic blood pressure (SBP) was measured monthly by the
      tail/cuff method. At the end of the experiment all the animals were sacrificed
      for microscopic studies. Cavernous tissue was processed by hematoxylin and eosin,
      Masson's trichrome, and monoclonal anti-alpha smooth muscle actin. Cavernous
      smooth muscle (CSM) and vascular smooth muscle (VSM) proliferation and CT
      fibrosis were evaluated by a semiquantitative score. SHR showed a higher
      proliferative score in CSM (2.7 +/- 0.28 v 1.1 +/- 0.07; P < .001), as well as in
      VSM (2.7 +/- 0.25 v 1 +/- 0.05; P < .001), and higher CT fibrosis score (2.8 +/-
      0.28 v 0.1 +/- 0.07; P < .001), when compared to WKY rats. Furthermore, SHR
      showed a positive correlation between SBP and CSM proliferative score (r2 =
      0.9277), SBP and VSM proliferative score (r2 = 0.8828), and SBP and CT fibrosis
      score (r2 = 0.7775). In addition, an increase in the surrounding connective
      tissue at the perineurium and endoneurium of the amielinic nerves in CT was
      observed in the SHR group. According to these results we conclude that SHR
      present morphologic changes in vessels as well as in cavernous spaces of the
      erectile tissue that have a high positive correlation with high blood pressure.
      Moreover, the increase in extracellular matrix expansion seems to affect not only
      the interstitium but also the neural structures of the penis.

PMID- 10912755
TI  - Lack of association between a biallelic polymorphism in the adducin gene and
      blood pressure in whites and African Americans.
AB  - Population-based candidate gene association analyses are becoming increasingly
      popular as a result of a greater number of genes and gene polymorphisms having
      been identified for which some functional information is available. Because many
      biochemical and physiologic systems impact blood pressure regulation and
      hypertension susceptibility, many of these identified genes and polymorphisms are
      candidates for population-level association studies involving blood pressure
      levels or hypertension status. Recent studies have suggested that the alpha
      adducin gene may harbor polymorphisms that influence blood pressure level.
      Therefore, we embarked on a study to test one such polymorphism in two large US
      samples: one from an urban African American population (Maywood, IL) and another
      from a rural white population (Tecumseh, MI). We used both family-based
      association tests and tests that consider the impact of additional measured
      factors beyond adducin gene variation on blood pressure levels. We found no
      evidence for a significant effect of the chosen adducin polymorphism on blood
      pressure variation in either sample. We also found no association between Adducin
      genotypes and antihypertensive use. These facts, together with similar findings
      in companion studies, suggest that the alpha-adducin gene polymorphism does not
      have a pronounced effect on blood pressure variation in the populations studied.
      This does not suggest, however, that the alpha-adducin gene does not have a role
      in blood pressure regulation and hypertension susceptibility.

PMID- 10912756
TI  - Association and linkage analysis of the alpha-adducin gene and blood pressure.
AB  - In Milan hypertensive rats, a variant in the alpha-adducin gene has been shown to
      account for approximately 50% of the interindividual variation in blood pressure
      levels between these animals and their normotensive counterparts. Additional
      studies have suggested that a polymorphism within exon 10 of the human alpha
      adducin gene (Gly-460-Trp) may be associated with hypertension and salt
      sensitivity. On the basis of these observations, we investigated variation within
      or near the human alpha-adducin gene for linkage and association with a locus
      influencing blood pressure levels in 281 nuclear families (774 siblings aged 5 to
      37 years; 380 parents aged 26 to 57 years), selected from the white population of
      Rochester, Minnesota, without regard to health. Sib pair linkage analyses (n =
      852 sibling pairs) using a dinucleotide repeat marker (D4S43) that maps
      approximately 660 kb from the alpha-adducin gene provided no evidence of linkage
      between this marker locus and a locus influencing systolic, diastolic, or mean
      blood pressure levels. Allele frequencies for the Gly-460-Trp polymorphism were
      similar to those reported in other white populations (Gly = 0.812, Trp = 0.188);
      however, this polymorphism was not associated with any measure of blood pressure
      level in either parents or siblings. Therefore, variation within the alpha
      adducin gene does not appear to have a major influence on measures of blood
      pressure in white families from Rochester, Minnesota.

PMID- 10912757
TI  - Lack of evidence for an association between alpha-adducin and blood pressure
      regulation in Asian populations.
AB  - Recent studies have found the tryptophan allele of a glycine to tryptophan
      polymorphism at position 460 (G460W) of the alpha-adducin protein to be
      associated with essential hypertension in European populations. We examined
      whether the tryptophan allele is associated with hypertension in a different
      population, comprised of subjects of Chinese origin from Taiwan, and Chinese and
      Japanese origin from the San Francisco Bay area and Hawaii. We adapted the 5'
      allelic discrimination assay or TaqMan to type individuals for the G460W
      polymorphism, and using this method we typed more than 1000 individuals. The
      frequency of the W allele was slightly increased in the treated subjects in the
      Chinese population (0.458 v 0.423) but not the Japanese population (0.549 v
      0.558). We considered dominant, recessive, and additive models in our analysis.
      There was a significant result for a recessive model for systolic blood pressure
      in the Chinese population (chi2 6.84, df = 2, P < .05), but only suggestive
      evidence for diastolic blood pressure (chi2 3.30). In contrast, in the Japanese
      population, there was no evidence for a positive association under any model. For
      the combined Chinese and Japanese samples, the evidence for association with
      alpha-adducin was not significant.

PMID- 10912758
TI  - Association between the alpha-adducin gene and hypertension in the HyperGEN
      Study.
AB  - This report from the HyperGEN Study, one of four networks participating in the
      NHLBI-sponsored Family Blood Pressure Program, presents the results of an
      association study based on 822 white and 572 black subjects (cases and controls)
      participating in the HyperGEN Network from five geographically diverse field
      centers. All cases met the Joint National Committee on Detection and Treatment of
      High Blood Pressure (JNC VI) criteria for hypertension (Stage I or higher). Each
      subject was clinically examined for risk factors for hypertension as well as
      genotyped for the point mutation Gly460Trp at the alpha-adducin locus on
      chromosome 4p. In the white group, the prevalence of genotypes with one or more
      Trp alleles was 26% in normotensives, versus 33% in hypertensives randomly
      selected from the population, and 39% among the multiply affected hypertensive
      sibships. Overall, in whites, the Trp allele significantly increased the odds of
      hypertension (P = .0056), with an odds ratio (OR) of 1.73 (95% confidence
      interval [CI] = 1.17, 2.54). The alpha-adducin gene remained a significant
      independent predictor of hypertension in a multivariate logistic model even after
      correcting for other risk factors for hypertension, including gender, age, body
      mass index (BMI), smoking, LDL cholesterol, triglycerides, urine sodium (Na), and
      urine potassium (K), (OR = 1.55, 95% CI = 1.03, 2.34). Through the use of
      regression trees, several gene-by-environment interactions were implicated,
      suggesting that alpha-adducin appears to be a particularly important risk factor
      (OR = 4.2) for older (age > 60.5 years), less lean (BMI < 25.8 kg/m2) subjects
      with moderately high triglycerides (between 145.5 and 218.5 mg/dL). In the black
      group, the relationship was less clear. Overall, it was protective against
      hypertension. The prevalence of genotypes with one or more Trp alleles was 24%
      among normotensive versus 11% in hypertensive black subjects randomly selected
      from the population, and 13% among multiply affected hypertensive sibships,
      resulting in an OR of 0.48 (P = .0231; 95% CI = 0.25, 0.90). However, the Trp
      genotype was no longer a significant independent predictor of hypertension risk
      in the multivariate logistic model (OR = 0.79; 95% CI = 0.37, 1.67), suggesting
      that it may be operating through one or more of these other factors. Thus, we
      conclude that the alpha-adducin gene is a significant, independent risk factor
      for hypertension in whites, but not in blacks, and may play a particularly
      important role for subjects with certain constellations of other risk factors.

PMID- 10912759
TI  - Alpha-adducin polymorphism in hypertensives of South African ancestry.
AB  - The alpha-adducin gene contributes significantly to hypertension in MHS rats
      (rats of the Milan hypertensive strain) and in some white and Japanese
      populations, causing a low renin, sodium, and diuretic-sensitive hypertension. No
      data are available from populations of African ancestry who have a high
      prevalence of low renin, sodium, and diuretic-sensitive hypertension. We studied
      the relationship between the 460-Trp variant of alpha-adducin gene with
      hypertension using a case-control study design in black South Africans.
      Surprisingly we found that the overall frequency of the 460-Trp allele was low
      (approximately 6%), but in spite of such relatively low frequency, the 460-Trp
      allele was 2.5-fold more frequent in hypertensives than normotensives (P = .028),
      with an odds ratio for hypertension associated to the state of carrier of at
      least one 460-Trp allele of 2.68. The finding of such low frequency of the 460
      Trp allele in individuals of African ancestry points to the substantial ethnic
      variability of the genes that have been found to be associated with hypertension.
      On the other hand, it suggests an association of the 460-Trp allele with
      hypertension also in subjects of African origin.

PMID- 10912760
TI  - Pretreatment blood pressure as a predictor of 21-year mortality.
AB  - Our objective was to evaluate pretreatment predictors of longevity, particularly
      blood pressure, in a large cohort of hypertensive men. During 1974 to 1976,
      10,367 male hypertensive veterans (47% black) were identified at screening and
      subsequently characterized in 32 special Veterans Administration (VA)
      hypertension clinics. Their mean age was 52 years and mean blood pressure (BP)
      154/100 mm Hg. During an average of 21 years of follow-up, 61% died. Risk ratios
      for all-cause mortality as functions of BP and other risk factors are presented
      for each variable alone; for each variable controlling for age, race, and BP; and
      for a multivariate model. We observed that when the entire cohort was divided
      into deciles by systolic blood pressure (SBP) and by diastolic blood pressure
      (DBP), the risk ratios for 21-year mortality increased from lowest to highest
      decile by 178% for SBP and 16% for DBP. When the deciles were computed separately
      by age group, increases from lowest to highest decile for those less than 40
      years of age were 138% for SBP and 263% for DBP. For those over 60 years, the
      increases were 154% and -10%, respectively. Although blacks were younger and had
      more severe diastolic hypertension than whites, the risk ratios were similar
      within each race group. Risk patterns for mean arterial pressure and pulse
      pressure resembled those for SBP but had smaller gradients. Survival curves for
      BP groups suggested constant mortality rates during follow-up. Other significant
      observations included decreasing mortality with increasing body mass index and
      increased mortality in the Stroke Belt. We concluded that pretreatment SBP
      strongly predicted all-cause mortality during 21-year follow-up. For the young,
      both SBP and DBP were strong predictors; for the elderly, only SBP was
      predictive.

PMID- 10912761
TI  - All for one and one for all: introduction to a coordinated analysis of the Gly
      460-Trp alpha-adducin polymorphism.

PMID- 10912762
TI  - The risks of hypertension: a renewed call for high blood pressure control.

PMID- 10912763
TI  - Association and linkage analysis of alpha-adducin polymorphism: is the glass half
      full or half empty?

PMID- 10912764
TI  - Intrarenal angiotensin II augmentation in angiotensin II dependent hypertension.
AB  - In several models of angiotensin II (ANG II) dependent hypertension, intrarenal
      ANG II levels increase to a much greater extent than the circulating levels even
      though the renal renin levels are decreased. The 2-kidney-1-clip (2K1C) Goldblatt
      rat model is particularly intriguing because hypertension develops in the
      presence of an intact kidney which would be expected to maintain sodium balance
      and protect against hypertension. Although the non-clipped kidney becomes renin
      depleted, it exhibits enhanced microvascular reactivity and increased tubular
      fractional sodium reabsorption. The non-clipped kidney ANG II content is either
      elevated or unchanged and proximal tubular fluid ANG II concentrations are not
      suppressed compared to the nanomolar concentrations found in normal rats. These
      results suggest that intrarenal ANG II content can be regulated independently of
      renal renin content. A similar hypertensive process occurs in rats infused
      chronically with low doses of ANG II. Renal ANG II content increases over 14 days
      to a greater extent than the circulating concentrations. Functionally, ANG II
      infused rats demonstrate reduced sodium excretion and marked suppression of
      pressure natriuresis. These ANG II dependent influences on kidney function
      contribute to the maintenance of hypertension. Renal augmentation of ANG II,
      hypertension, and suppressed sodium excretion are blocked by AT1 receptor
      blockers. To study the mechanisms responsible for intrarenal ANG II augmentation,
      we infused a different form of ANG II (Val5 ANG II), that can be separated from
      endogenous ANG II by HPLC. These results indicated that the increased renal ANG
      II content was due to accumulation of circulating ANG II in addition to continued
      production of endogenous ANG II. The renal accumulation of Val5-ANG II was
      markedly reduced by concomitant treatment with the AT1 receptor blocker,
      losartan. In addition, we found an unchanged overall ANG II-AT1 receptor protein
      which probably contributes to the maintained ANG II dependent influences.
      Collectively, the data support the concept that there is internalization of ANG
      II through an AT1 receptor mediated process and that some of the internalized ANG
      II is protected from degradation. The augmented intrarenal ANG II coupled with
      sustained levels of AT1 receptors contribute to the continued ANG II dependent
      suppression of renal function and sodium excretion thereby maintaining the
      hypertension.

PMID- 10912766
TI  - Left ventricular mass predicted by a single reading of ambulatory blood pressure
      in essential hypertension.
AB  - The spectral power of heart rate variability has been shown to be negatively
      correlated with left ventricular mass (LVM), suggesting the contribution of left
      ventricular hypertrophy to autonomic dysfunction in essential hypertension.
      However, a simultaneous assessment of autonomic function and ambulatory blood
      pressure in relation to LVM has not been carried out. The objective of the
      present study was to elucidate the synergistic effects of ambulatory blood
      pressure and autonomic nerve activity on the heart. We enrolled 25 ambulant
      patients with untreated essential hypertension (9 men and 16 women; mean age 50.6
      +/- 2.0 years). The ambulatory blood pressure and heart rate variability were
      simultaneously monitored every 30 min for 24 h. The spectral power of high
      frequency (HF: 0.15 to 0.4 Hz) and low-frequency (LF: 0.05 to 0.15 Hz) bands were
      measured, and the ratio of LF to HF (LF/HF) was calculated. LF/HF and HF were
      used as indexes of sympathetic and parasympathetic activities, respectively. LVM
      was determined by echocardiography. Both the average daytime and nighttime
      systolic ambulatory blood pressures significantly correlated with the LVM index
      (r= 0.644, p< 0.001; and r= 0.428, p< 0.05; respectively), although there was no
      such correlation with the clinic blood pressures. In contrast, a single reading
      of ambulatory systolic blood pressure measured when LF/HF reached a maximum value
      was significantly correlated with the LVM index independently of age and sex
      (partial r= 0.484, p< 0.05). These results suggest that the ambulatory systolic
      blood pressure during increases in the activity of the sympathetic nervous system
      is able to infer LVM in essential hypertension.

PMID- 10912765
TI  - Sympathetic activity and body mass index contribute to blood pressure levels.
AB  - The purpose of this study was to clarify the relationships between obesity (BMI)
      and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a
      Japanese male population. In 912 young, non-diabetic, Japanese men with a wide
      range of BMI (16.5-33.6 kg/m2), blood pressure (BP), fasting plasma
      norepinephrine (NE), insulin and leptin levels were measured after an overnight
      fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The
      study was carried out using a cross-sectional design. When the subjects were
      subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group
      (BMI > 27.9 kg/m2) had a significantly higher systolic BP (p< 0.05) and pulse
      rate (p< 0.05) as well as higher NE (p< 0.01), insulin (p< 0.01), and leptin (p<
      0.01) levels than 86 subjects in the leanest group (BMI < 22.2 kg/m2). In the
      whole cohort, BMI correlated with mean BP (p< 0.01), plasma NE (p< 0.05), insulin
      (p< 0.001) and leptin (p< 0.001). The mean BP correlated with BMI (p< 0.001),
      plasma NE (p< 0.01), insulin (p< 0.01) and leptin (p< 0.05). Plasma leptin levels
      correlated with fasting plasma insulin levels (p < 0.05), but not with plasma NE
      levels (NS). As analyzed by multiple regression analysis, only plasma NE (p<
      0.05) and BMI (p< 0.001), but not plasma insulin levels, were significant,
      independent predictors of BP levels (r2=0.125, F= 10.51, p=0.0001). These results
      suggest that obesity (BMI) and heightened sympathetic nervous system activity
      contribute to BP elevation (hypertension).

PMID- 10912767
TI  - The regression of left ventricular hypertrophy by imidapril and the reduction of
      serum procollagen type III amino-terminal peptide in hypertensive patients.
AB  - Angiotensin-converting enzyme (ACE) inhibitors are known to be the most effective
      antihypertensive drugs for reducing left ventricular mass in hypertensives when
      compared to other classes of drugs. In the present study, we evaluated the
      effects of imidapril, an ACE inhibitor, on serum procollagen type III amino
      terminal peptide (PIIIP) levels as well as the left ventricular mass index
      (LVMI). The subjects consisted of 15 patients (12 men and 3 women) in the
      outpatient clinic of our hospital who were diagnosed as essential hypertensives
      and who had not been treated with any antihypertensive medication prior to the
      study. Left ventricular hypertrophy was observed in all of the patients, ie.,
      LVMI >110 g/m2 in men and >106 g/m2 in women. Blood pressure, LVMI, and serum
      PIIIP levels were measured before and after treatment with imidapril for 6
      months. The starting dose of imidapril was 5 mg, and this was increased to 10 mg.
      Finally, 1 mg of trichlormethiazide was added to obtain adequate control of blood
      pressure. Blood pressure significantly decreased in 12 patients, and the mean
      LVMI decreased significantly from 153.1 +/- 9.0 to 135.4 +/- 6.3 (p< 0.01) after
      treatment. The changes in LVMI and PIIIP levels with treatment had significant
      correlation (r=0.639, p< 0.05). The present study showed that imidapril reduces
      the left ventricular mass in hypertensives after 6 months of treatment, and that
      this may at least in part be due to a decrease in the collagen content of the
      hypertrophied heart, suggesting that serum PIIIP levels are a useful marker of
      the regression of left ventricular hypertrophy.

PMID- 10912768
TI  - Prognostic value of nighttime blood pressure in the elderly: a prospective study
      of 24-hour blood pressure.
AB  - Although it has been suggested in several reports that 24-h ambulatory blood
      pressure (BP) is a better predictor than casual BP measured in a clinician's
      office of the incidence of cardiovascular (CV) events, little information is
      available concerning the prognostic value of nighttime BP in the elderly
      population. Therefore, to evaluate the clinical implications of the nighttime BP
      in the elderly, we prospectively followed-up 324 elderly individuals (mean age,
      77.2 +/- 7.0 years) who had undergone ambulatory BP monitoring at an annual
      health examination over a mean follow-up period of 51.5 +/- 22.0 months, and the
      relationship between BP and CV events was analyzed using Cox's proportional
      hazard model. For the analysis, 310 participants, excluding 14 subjects who were
      withdrawn due to non-CV events, were classed into two groups, one consisting of
      134 individuals who were undergoing treatment with an anti-hypertensive drug
      (medicated group) and another consisting of 176 who were not medicated
      (nonmedicated group). New cardiovascular events developed in 43 cases in the
      medicated group and in 14 cases in the non-medicated group during the follow-up
      period. In the medicated group, a linear relationship was observed between BP and
      the event rates. The hazard ratio for CV events adjusted for age, sex, and other
      cardiovascular risks was 1.28 (95% confidence interval [CI], 1.05 to 1.54, p<
      0.05) for a 10 mmHg increase of 24-h systolic BP. Corresponding values in 24-h
      diastolic BP, nighttime systolic BP, and nighttime diastolic BP were 1.71 (1.19
      to 2.46, p< 0.01), 1.34 (1.13 to 1.58, p< 0.01), and 1.67 (1.20 to 2.31, p<
      0.01), respectively. In the non-medicated group, the event rate was least in the
      subgroup in the second-lowest quartile for nighttime systolic BP, with a slight
      non-significant increase in the subgroup of the lowest quartile. It was shown
      that insufficient control of nighttime BP in the elderly with hypertension is
      associated with the development of CV complications.

PMID- 10912769
TI  - Simultaneous intravascular two-dimensional plus Doppler ultrasound is useful for
      evaluation of postischemic vasodilatation: plasm NOx - levels determined by the
      Griess method may not reflect the extent of postischemic NO-induced
      vasodilatation.
AB  - Our objective was 1) to assess postischemic vasodilatation using simultaneous
      intravascular two-dimensional and Doppler ultrasound, and 2) to clarify whether
      plasma nitrite and nitrate (NOx-) levels change during postischemic
      vasodilatation. The vascular cross-sectional area (CSA) was evaluated in 18
      mongrel dogs, and the average instantaneous peak velocity (APV) in the iliac
      arteries after the 5-min occlusion of blood flow was determined. Plasma NOx-
      levels were measured at the baseline, during the occlusion of blood flow, and
      1.5, 3, and 10 min after recanalization. The %CSA significantly increased from 30
      s to 7 min after the recanalization, and maximal vasodilatation was observed at
      1.5 min after the recanalization (14.1 +/- 0.9 to 15.8 +/- 1.0 mm2, p< 0.0001 vs.
      baseline). Plasma NOx- levels were significantly reduced during the occlusion of
      blood flow and remained reduced at 1.5, 3, and 10 min after recanalization
      compared with the baseline values. We concluded that simultaneous intravascular
      two-dimensional and Doppler ultrasound is useful for assessment during
      postischemic vasodilatation, and that plasma NOx- levels assayed with the Griess
      reagent do not significantly increase, even when maximal vasodilatation is
      observed.

PMID- 10912771
TI  - Cardiomyocyte functions couple with left ventricular geometric patterns in
      hypertension.
AB  - Previous studies have suggested the prognostic significance of left ventricular
      (LV) geometric patterns in essential hypertension. However, the relation between
      cardiomyocyte functional changes and LV geometric patterns has not been
      clarified. This study was designed to assess the morphological and functional
      changes in isolated myocytes derived from different LV geometric patterns in
      hypertension. After 2-3 weeks of a high-salt (8%) diet from the age of 6 weeks,
      20 Dahl salt-sensitive (DS) rats were classified into the following three groups
      on the basis of an echocardiographically determined LV mass index and the
      relative wall thickness: concentric hypertrophy (11), eccentric hypertrophy (4),
      and concentric remodeling (5). Ten Dahl salt-resistant (DR) rats served as
      controls. In vivo LV functions were assessed based on echocardiographic
      measurements. We examined ventricular myocytes isolated from all groups. To
      evaluate the force-frequency relation, cardiomyocytes isolated from all groups
      were paced at stimulation rates of 0.3, 0.5, 1.0, 2.0, and 3.0 Hz. Concentric
      hypertrophy and eccentric hypertrophy groups exhibited an increase in myocyte
      width but no changes in the length. Concentric hypertrophy and concentric
      remodeling groups demonstrated in vivo LV dysfunction. In addition, DS rats,
      especially these with concentric hypertrophy, demonstrated impaired frequency
      responses in terms of both myocyte contraction and relaxation compared with DR
      rats. This impaired force-frequency relationship was especially remarkable at
      high frequencies. These findings suggest that the structural and functional
      changes in cardiomyocytes are closely related to the LV geometric pattern and may
      contribute to a different prognosis according to different geometric patterns.

PMID- 10912770
TI  - Central infusion of L-arginine or superoxide dismutase does not alter arterial
      pressure in SHR.
AB  - Cardiovascular responses to L-arginine and nitric oxide (NO) are augmented in the
      rostral ventrolateral medulla (RVLM) of spontaneously hypertensive rats (SHR),
      and the intravenous injection of superoxide dismutase (SOD) mimetic decreases the
      arterial pressure in these rats. In the present study, we examined whether the
      chronic central infusion of L-arginine or an SOD mimetic would reduce the blood
      pressure of SHR and alter responses to an NOS inhibitor or an NO donor in the
      RVLM. For this purpose, we administered L-arginine (SHR-Arg: 13.2 micromol/day,
      n=6), a stable membrane-permeable SOD mimetic, 4-hydroxy-2, 2,6,6-tetramethyl
      piperidine-1-oxyl (tempol) (SHR-Temp: 13.2 micromol/day, n=6), or vehicle (SHR-C:
      n=6) into the lateral ventricle of 12-week-old SHR for 2 weeks. When the rats
      reached 14 weeks of age, N(G)-nitro-L-arginine methyl ester (L-NAME: 10 nmol/50
      nl) or NOC 18 (NO donor: 10 nmol/50 nl) was microinjected into the unilateral
      RVLM. Blood pressure did not decrease in any of the treatment groups (SHR-Arg:
      209+/-4 mmHg, SHR-Temp: 210+/-6 mmHg, SHR-C: 197+/-6 mmHg). The microinjection of
      L-NAME into the RVLM induced a significant increase in the mean arterial pressure
      (MAP) (SHR-Arg: 10-4 mmHg, SHR-Temp: 12+/-4 mmHg, SHR-C: 11+/-3 mmHg), and the
      increases in MAP did not differ among the groups. The micro-injection of NOC 18
      reduced MAP (SHR-Arg: -12+/-2 mmHg, SHR-Temp: -15+/-3 mmHg, SHR-C: -13+/-3 mmHg),
      and the depressor responses were comparable among groups. These results do not
      support the hypothesis that chronic L-arginine deficiency or the enhanced
      degeneration of NO by superoxide radicals in the central nervous system
      contributes to the maintenance of arterial pressure in SHR.

PMID- 10912772
TI  - Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a
      rat model of chronic inhibition of nitric oxide synthesis by its cholesterol
      lowering independent actions.
AB  - Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3
      methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin may be through
      their cholesterol-lowering independent effects on the blood vessels. We have
      recently reported that chronic inhibition of nitric oxide (NO) synthesis with
      N(omega)nitro-L-arginine methyl ester (L-NAME) increases systolic blood pressure
      and induces coronary vascular inflammatory changes in rats. We designed this
      study to investigate whether treatment with pravastatin attenuates such
      proarteriosclerotic changes through their cholesterol-lowering independent
      effects. Several groups of Wistar-Kyoto rats were studied: the control group, L
      group received L-NAME in their drinking water (100 mg/kg per day) and L+Px group
      received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed
      marked increases in monocyte infiltration into the coronary arteries,
      proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant
      protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration
      began. Treatment with pravastatin did not affect serum cholesterol levels or
      systolic blood pressure but did reduce the L-NAME induced inflammatory and
      proliferative changes. Pravastatin also attenuated the MCP-1 gene expression
      induced by L-NAME. In summary, pravastatin inhibited the inflammatory and
      proliferative changes in the coronary vessels through their cholesterol
      independent effects in this model, which may provide an insight into the
      mechanisms of anti-inflammatory or anti-arteriosclerotic actions of pravastatin.

PMID- 10912774
TI  - Assessment of autonomic function in patients with acute myocardial infarction or
      diabetes mellitus by heart rate variability, ventricular late potential and QT
      dispersion.
AB  - To compare the efficacy and sensitivity of heart rate variability (HRV), QT
      dispersion (QTd) and ventricular late potential (VLP) examination in judging
      autonomic function. Thirty three patients with acute myocardial infarction (AMI)
      and 33 patients with diabetes mellitus (DM), all of whom were diagnosed with
      autonomic neuropathy determined by a standard test of cardiovascular autonomic
      function, were examined by HRV (timing domain methods), QTd and VLP. Thirty three
      normal individuals served as controls. The mean SD of the normal R-R interval
      (SDNN) in both the AMI and DM groups was significantly less than that in the
      control group (p< 0.01); and of course, the QTd of these groups was significantly
      greater than that of the controls (p< 0.01). The VLP positive rate of the AMI and
      DM groups were much higher than that of the control group (p< 0.001). SDNN was
      shown to be significantly negatively correlated to QTd (r= -0.45); and
      significantly negatively correlated to VLP (r= -0.47); QTd was shown to be
      positively, though not significantly, correlated to VLP (r=0.48). QTd could be
      looked as sieving index; HRV could be looked as routine examination of
      cardiovascular autonomic function, especially SDNN; the combination of HRV and
      VLP could improve the accuracy of diagnosis.

PMID- 10912773
TI  - Cardiovascular responses to glutamate and angiotensin II in ventrolateral medulla
      of hypertension induced by chronic inhibition of nitric oxide.
AB  - It has been suggested that nitric oxide (NO) influences the actions of L
      glutamate and angiotensin II in the brain. In the present study, we examined
      whether cardiovascular responses to L-glutamate and angiotensin II would be
      altered in the rostral ventrolateral medulla (RVLM) of rats treated with an NO
      synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Wistar rats were
      treated with either L-NAME (100 mg/kg/day, n=9) or vehicle (n=8) for 4 weeks. L
      glutamate (2 nmol/50 nl) or angiotensin 11 (100 pmol) was then microinjected into
      unilateral RVLM of anesthetized rats. Upon completion of the experiments,
      angiotensin-converting enzyme (ACE) activity of the brain stem was measured. The
      systolic blood pressure after 4 weeks of the treatment was significantly higher
      in the L-NAME group (203+/-8 mmHg) than in the control group (142+/-3 mmHg, p<
      0.01). The pressor response to L-glutamate microinjected into the RVLM was
      significantly greater in the L-NAME group (31+/-2 mmHg) than in the control group
      (24+/-1 mmHg, p< 0.01). Similarly, angiotensin II showed a greater pressor
      response in the L-NAME group. ACE activity of the brain stem did not differ
      between the groups. In conclusion, NO may have an inhibitory influence on the
      actions of L-glutamate and angiotensin II in the RVLM.

PMID- 10912775
TI  - Relation between left ventricular geometric alteration and extracardiac target
      organ damage in hypertensive patients.
AB  - To study the relation between left ventricular geometric alteration and
      extracardiac target organ damage in hypertensive patients. A retrospective study
      of 298 patients with essential hypertension was performed. Left ventricular mass
      index (LVMI) and relative wall thickness (RWT) were calculated using
      echocardiographic data. Patients were divided into four groups based on their
      left ventricular geometric pattern as determined using LVMI and RWT. Each of the
      four left ventricular geometric patterns was associated with a different degree
      of extracardiac organ damage. In multivariate analysis, LVMI and RWT showed
      strong, significant correlation to retinal changes and increases in serum
      creatinine levels, respectively. Alteration of left ventricular geometry resulted
      in an increase in the degree of extracardiac target organ damage.
      Echocardiographic classification of left ventricular geometry can further
      stratify hypertensive patients according to risk, and possibly according to the
      indications for intensive treatment.

PMID- 10912776
TI  - Relationship between hypertensive left ventricular hypertrophy and levels of
      endothelin and nitric oxide.
AB  - To investigate the relationship between hypertensive left ventricular hypertrophy
      (LVH) and levels of endothelin (ET) and nitric oxide (NO), and to provide an
      experimental basis for prevention and treatment of hypertensive LVH. Fifty eight
      hypertensive patients and 14 healthy controls were studied. All patients were
      examined by echocardiography. Left ventricular mass (LVM) and left ventricular
      mass index (LVMI) were calculated using Devereux RB formula. Hypertensive
      patients were divided into a LVH (+) group (n= 21) and a LVH (-) group (n=37),
      and the levels of endothelin and nitric oxide in the peripheral venous blood were
      measured. The mean ET level was significantly higher in the LVH (+) group than in
      LVH (-) group (p < 0.05), but the NO level was significantly lower in the LVH (+)
      group. The ET/NO ratio was significantly higher in the LVH (+) group than in LVH
      (-) group (p< 0.01). For the stepwise multiple regression analysis, the LVMI of
      hypertensive patients served as a dependent variable, and age, sex, BMI, MAP, ET,
      NO, and ET/NO served as independent variables. Only MAP, ET, and NO were found to
      have significant correlation to hypertensive LVH. ET had a significant positive
      correlation, and NO a significant negative relation to LVMI, but ET/NO showed no
      correlation to hypertensive LVH. ET and NO are involved in hypertensive LVH; the
      independent action of ET and NO in the pathogenesis of hypertensive LVH may
      weaken the relation between ET/NO and hypertensive LVH.

PMID- 10912777
TI  - Dual effect of heparin and low molecular weight heparin on cultured smooth muscle
      cells.
AB  - The effects of heparin and low molecular weight heparin (LMWH) on the growth of
      cultured human aortic smooth muscle cells (hASMCs) were studied. The fourth
      passage hASMCs were planted onto a 24-well plate (5 wells for each concentration
      of heparin or LMWH) and cultured by DMEM containing 5% either old or fresh human
      serum (HS), 10% fetal calf serum (FCS), and differing concentrations of heparin
      or LMWH (heparin and LMWH were presented as hexuronic acid) together with
      corresponding control groups (without heparin or LMWH) for 24h. hASMCs growth was
      estimated both morphologically and by 3H-TdR incorporation. The results revealed
      that both heparin and LMWH inhibited the proliferation of healthy growth hASMCs,
      but promoted the proliferation of weak growth hASMCs. These results suggest for
      the first time that heparin and LMWH have a dual regulative role (inhibition and
      promotion) in hASMCs growth and indicate that they may play an important role in
      controlling the proliferation of vascular smooth muscle cells and maintaining the
      integrity of vascular structure.

PMID- 10912778
TI  - Human renin mRNA expression and renin activity in transgenic mice.
AB  - The renin-angiotensin system (RAS) plays a very important role in the regulation
      of blood pressure and electrolyte homeostasis in mammals. It has also been
      hypothesized to regulate local tissue and organ blood supply in an
      autocrine/paracrine manner. To further study RAS physiology, transgenic mice
      carrying the human renin gene were produced by microinjection and were screened
      by PCR. The human renin transgene was found, by RT-PCR, to be expressed in the
      heart, kidney, and lung of transgenic mice, but not in the liver or skeletal
      muscle. The mean levels of renin activity in various tissues were determined by
      radioimmunoassay. The mean level of renin activity in the plasma and the
      heart/body weight ratio of the transgenic mice (n=7) were also found to be
      significantly higher (p< 0.05) than those of the control mice (n= 8). However, no
      significant differences were seen in the mean levels of renin activities in the
      kidney and heart between transgenic and control mice. Thus, the transcription of
      human renin gene in transgenic mice is regulated in a tissue-specific manner.
      This transgenic model will be useful in clarifying the regulatory mechanisms of
      the renin gene and the relationship between this gene and diseases.

PMID- 10912780
TI  - Potential role of macrophage colony-stimulating factor in the proliferation of
      DEL cells.
AB  - The replication and activation of both vascular smooth muscle cells and
      macrophages, which have previously entered the arterial wall, are key events in
      the atherosclerotic process. The importance of macrophage colony-stimulating
      factor (MCSF) in control of the growth/proliferation of both cell types confers
      to this compound a central role in the development of vascular lesions. In order
      to gain insight into the mechanisms of macrophage proliferation, we investigated
      the effect of MCSF upon the proliferation of DEL cells. DEL cells constitute a
      monocyte/histiocytic cell line that differentiates along a macrophage lineage
      following exposure to phorbol ester. DEL cells constitutively express MCSF, and
      its receptor MCSFR is encoded by c-fms. We examined whether MCSF might play a
      role in the proliferation of cultured DEL cells. [3H]Thymidine or 5-bromo-2
      deoxyuridine (BrdU) incorporation was measured following the addition of
      recombinant MCSF or L929 cell supernatant (as a source of MCSF) to quiescent DEL
      cells. In DEL cells, serum-free L929 cell supernatant induced DNA synthesis in a
      dose-dependent manner, and such an effect could be blunted by pretreatment of
      L929 cell supernatant with anti-mouse MCSF antibody. In these cells, DNA
      synthesis could also be triggered in a dose-dependent manner by the addition of
      recombinant human MCSF (rh MCSF) or thrombin. These findings clearly show that
      MCSF influences DEL cell proliferation and suggest an autocrine loop activation.
      They indicate that MCSF plays an important role in the development of vascular
      lesions, which occur during atherosclerotic progression.

PMID- 10912779
TI  - Renal protective effects of blocking the intrarenal renin-angiotensin system:
      angiotensin II type I receptor antagonist compared with angiotensin-converting
      enzyme inhibitor.
AB  - The present study compared renoprotective effects of angiotensin II type I
      receptor antagonist (AT1RA) with angiotensin converting enzyme inhibitor (ACEI),
      and their influence on the renin-angiotensin-system (RAS). Experimental nephrotic
      syndrome was induced in SD rats by repeated peritoneal injections of puromycin.
      Twenty-eight rats were randomly divided into four groups: normal control,
      nephrotic control, ACEI-treated, and AT1RA-treated groups. Serum, urine, and
      renal tissue were collected for study at the end of 12 weeks. Compared with those
      of the nephrotic control group, urinary protein was less and renal function was
      better in both treated groups. The glomerular and interstitial damage indexes of
      both ACEI- and AT1RA-treated rats were lower than those of nephrotic control
      rats, with no significant difference observed between the two treated groups.
      Local renal ACE activity and angiotensin II concentration were elevated in
      nephrotic rats (p< 0.01). However, there is no significant difference in
      circulating RAS, renal tissue renin, and aldosterone between the normal control
      and nephrotic control rats. As expected, enalapril inhibited the local renal ACE
      activity and significantly decreased angiotensin II (p< 0.01). Intrarenal ACE
      activity and angiotensin concentration returned to normal levels after treatment
      with irbesartan (p< 0.01). In conclusion, AT1RA and ACEI have comparable renal
      protective effects, and these protective effects were associated with the
      inhibition of intrarenal ANG II.

PMID- 10912781
TI  - The inhibitory mechanisms of amlodipine in human vascular smooth muscle cell
      proliferation.
AB  - The abnormal proliferation of vascular smooth muscle cells (VSMCs) is closely
      related to vascular diseases. There is growing evidence that calcium antagonists
      inhibit VSMC growth/proliferation, yet their molecular mechanisms remain to be
      determined. Recent reports suggest that p42/p44 mitogen-activated protein kinases
      (MAPKs) play an important role in cell growth and proliferation induced by growth
      factors. This study was designed to determine whether these MAPKs are involved in
      VSMC proliferation induced by basic fibroblast growth factor (bFGF) and to
      examine the inhibitory effect of amlodipine. Human VSMCs were obtained from inner
      mammary artery. p42/p44 MAPKs activity was measured by immunoblotting assay using
      anti-p42/p44 phospho-MAPK antibody. 1) bFGF (20 ng/ml) significantly activated
      p42/p44 MAPKs with a peak time of 5-15 min, which was maintained for 3 h. PD98059
      (100 nM-10 microM), a specific inhibitor of MAPK kinase, inhibited bFGF-induced
      p42/p44 MAPKs activation in a dose-dependent manner. 2) Amlodipine (1-100 nM)
      dose-dependently inhibited p42/p44 MAPKs activation by bFGF. 3) Amlodipine (10
      nM) could inhibit both short-term and long-term p42/p44 MAPKs activation by bFGF.
      Our results indicate that bFGF could activate p42/p44 MAPKs. Amlodipine, which
      could inhibit bFGF-induced human VSMC proliferation, inhibited both short-term
      and sustained p42/p44 MAPKs activation by bFGF, suggesting that bFGF-induced VSMC
      proliferation may be related to p42/p44 MAPKs activation, and that the
      antiproliferative effect of amlodipine may be related to its inhibition of
      p42/p44 MAPKs activation.

PMID- 10912782
TI  - Signal transduction mechanisms linking increased extracellular calcium to
      proliferation in ovarian surface epithelial cells.
AB  - Although ovarian surface epithelial (OSE) cells are the cell type responsible for
      malignant ovarian carcinoma, relatively little is known about either the
      extracellular stimuli or the intracellular signaling mechanisms responsible for
      regulating proliferation in these cells. We have demonstrated that OSE cells
      proliferate in response to elevation of extracellular calcium and that OSE cells
      express functional calcium-sensing receptors (CaR). Here we show that agonists of
      the CaR increase the kinase activity of Src and ERKs (extracellular signal
      regulated kinases) in rat OSE cells and promote association between tyrosine
      phosphorylated Shc and p120rasGAP. Expression of an interfering mutant CaR
      inhibited the proliferative response to elevated extracellular calcium, as well
      as CaR agonist-induced tyrosine phosphorylation and ERK activation. Transfection
      with dominant negative mutants of Ras, Raf, and MKK1 also inhibited the increase
      in ERK activity in response to calcium, as did treatment with herbimycin, a
      selective inhibitor for Src family kinases. These results indicate that the
      ability of OSE cells to proliferate in response to increases in extracellular
      calcium involves cross-talk between the G-protein-coupled CaR and the activation
      of a tyrosine kinase-dependent Ras-Raf-ERK signaling pathway.

PMID- 10912783
TI  - Differentiation of mesothelioma cells is influenced by the expression of
      proteoglycans.
AB  - Malignant mesothelioma characteristically shows epithelial and/or sarcomatous
      morphology, this phenotypic differentiation being correlated to the prognosis.
      The present study was undertaken to see whether proteoglycan (PG) expression
      influences mesothelioma differentiation. To assess this hypothesis, we studied a
      mesothelioma model, where the cells were induced to differentiate into epithelial
      or fibroblast-like morphology, mimicking the biphasic growth of this sarcoma.
      Series of PGs were analyzed in parallel by semiquantitative reversed
      transcriptase polymerase chain reaction, showing increased expression of syndecan
      2, syndecan-4, and hyaluronan synthase in the epithelial phenotype, whereas the
      fibroblast-like cells expressed more matrix PGs: versican, decorin, and biglycan.
      Western blotting confirms these differences and provides evidence of extensive
      shedding and rapid turnover of cell membrane PGs. Experimental down-regulation of
      the studied syndecans by antisense targeting resulted in a change in shape from
      polygonal to spindle-like morphology, while syndecan-1 and -4, but not syndecan
      2, could be associated with cell aggregation, indicating distinct functions of
      different syndecans. The PG profile is thus closely associated with the
      morphology and biological behavior of tumor cells, mesotheliomas showing a
      different profile than true epithelial tumors.

PMID- 10912785
TI  - Human dentin production in vitro.
AB  - The main hard tissues of teeth are composed of dentin and enamel, synthesized by
      the mesenchyme-derived odontoblasts and the epithelial-derived ameloblasts,
      respectively. Odontoblasts are highly differentiated post-mitotic cells secreting
      the organic matrix of dentin throughout the life of the animal. Pathological
      conditions such as carious lesions and dental injuries are often lethal to the
      odontoblasts, which are then replaced by other pulp cells. These cells are able
      to differentiate into odontoblast-like cells and produce a reparative dentin. In
      this study we reproduced this physiological event in an in vitro culture system
      using pulps of human third molars. Pulp cells cultured in presence of beta
      glycerophosphate formed mineralization nodules, which grew all over the culture
      period. The immunohistochemical study revealed that, as odontoblasts, pulp cells
      contributing to the nodule formation express type I collagen, osteonectin, and
      nestin. By the exception of nestin, these proteins are also detected in the
      nodules. The composition of the nodules was also analyzed by Fourier transform
      infrared microspectroscopy. The spectra obtained showed that both the organic and
      the mineral composition of the nodules have the characteristics of the human
      dentin and differ from those of enamel and bone. Taken together, these results
      show that both the molecular and the mineral characteristics of the human dentin
      matrix are respected in the in vitro culture conditions.

PMID- 10912784
TI  - Caveolin-1 and -2 expression is differentially regulated in cultured
      keratinocytes and within the regenerating epidermis of cutaneous wounds.
AB  - Keratinocyte growth factor (KGF) and its receptor are involved in various types
      of epithelial repair processes. To gain insight into the molecular mechanisms of
      KGF action in the healing skin wound, we searched for genes which are regulated
      by this factor in cultured keratinocytes. Using the PCR-select technology we
      constructed a subtractive cDNA library. One of the KGF-regulated genes that we
      identified was shown to encode caveolin-1, a major component of caveolar
      membranes. Caveolin-1 is involved in a wide variety of cellular processes,
      particularly in the regulation of various signal transduction pathways. Caveolin
      1 mRNA levels increased in cultured keratinocytes after KGF treatment. By in situ
      hybridization and immunohistochemistry we found a strong expression of caveolin-1
      in the KGF-responsive basal keratinocytes of the epidermis and the
      hyperproliferative epithelium of the wound as well as in endothelial cells and in
      other cells of the granulation tissue. In 13-day wounds expression of caveolin-1
      mRNA was restricted to the regenerated dermis. In addition to caveolin-1, the
      mRNA expression of caveolin-2, a second member of the caveolin family, was also
      induced in keratinocytes after stimulation with KGF but also with other growth
      factors and cytokines. In contrast to caveolin-1, caveolin-2 protein was
      expressed in all layers of the normal epidermis and in the suprabasal layers of
      the hyperproliferative wound epithelium. These results demonstrate a differential
      expression of caveolin-1 and -2 in proliferating versus differentiating
      keratinocytes.

PMID- 10912786
TI  - The cell adhesion molecule retina cognin is a cell surface protein disulfide
      isomerase that uses disulfide exchange activity to modulate cell adhesion.
AB  - The retina cell adhesion molecule, R-cognin, shares cDNA sequence with protein
      disulfide isomerase (PDI) but has a different molecular size and subcellular
      location. We asked whether R-cognin originated from a unique PDI gene transcript
      or was a product of posttranscriptional processing. The 3'-terminal partial cDNA
      clone for R-cognin was extended by both 5' RACE and by PCR from sequence near the
      5' end of the PDI-translated region. The cDNA sequence was compared to those of
      chicken, bovine, and human PDI. The R-cognin cDNA sequence was identical to that
      of chicken PDI and differed by less than 10% from mammalian PDI proteins. The
      role of the disulfide exchange activity characteristic of both proteins was
      studied by assessing the cell-aggregation-enhancing ability and tissue
      specificity of R-cognin and recombinant human PDI and its derivatives. Chicken
      and normal human PDI proteins showed tissue- and developmental-specific
      enhancement of cell aggregation identical to R-cognin, and this activity was
      blocked by inactivation of the -WCGHC- motifs which function in disulfide
      exchange. Dependence of retina cell aggregation on disulfide exchange activity
      was shown by blocking that activity with the inhibitor, DTNB, or with a
      recombinant human PDI with the -WCGHC- motif cysteines mutated. The results
      suggest that one -WCGHC- motif in R-cognin is sufficient and that the more C
      terminal motif is most active. We conclude that R-cognin is a tissue-specific
      protein product of the standard PDI chicken gene. The -WCGHC- motif in mature R
      cognin is necessary, but not sufficient, for cell adhesion.

PMID- 10912787
TI  - Transcriptional control elements of the rat thymidylate synthase promoter:
      evolutionary conservation of regulatory features.
AB  - The sequence elements that are important for the transcription and regulation of
      the rat thymidylate synthase (TS) gene were analyzed. The rat TS promoter lacks a
      TATA box and directs transcriptional initiation at multiple sites between 60 and
      20 nt upstream of the AUG translational start codon. Promoter deletion analyses
      showed that the region between -100 and -42 nt relative to the AUG codon was both
      necessary and sufficient for high level promoter activity and was designated the
      essential promoter region. The essential region also had bidirectional promoter
      activity. Site-directed mutagenesis revealed that four elements were especially
      important for promoter activity. These include Ets motifs at -85 and -50, an Sp1
      motif at -80, and an LSF motif that overlapped the upstream Ets and Sp1 motifs.
      Inactivation of E2F motifs that are upstream and downstream of the essential
      promoter region had no measurable effect on promoter activity in transient
      transfection assays. The rat TS promoter region directed S-phase-specific
      expression of a stably transfected minigene if a spliceable intron was included
      in the transcribed region. When the intron was deleted or the E2F motifs were
      inactivated, expression of the minigene changed very little during the G1 to S
      transition.

PMID- 10912788
TI  - TNF-alpha suppresses the PDGF beta-receptor kinase.
AB  - PDGF and TNF-alpha are both known to play important roles in inflammation, albeit
      frequently by opposing actions. Typically, TNF-alpha can attenuate PDGF beta
      receptor signaling. Pretreatment of mouse 3T3 L1 fibroblasts with TNF-alpha
      greatly diminished their proliferative response to PDGF. However, TNF-alpha
      affected neither the binding of PDGF-BB to cell surface receptors nor the total
      amount of PDGF beta-receptor in the cells, but decreased the PDGF-induced in
      vitro kinase activity of the receptor. The phosphatase inhibitor ortho-vanadate
      did not prevent this effect. Ortho-phosphate labeling of cells prior to TNF-alpha
      treatment and PDGF-BB stimulation confirmed a decrease of in vivo phosphorylation
      of the PDGF beta-receptor. Two-dimensional mapping after tryptic cleavage as well
      as phosphoamino acid analysis demonstrated a general decrease in phosphorylation
      of all known tyrosine residues in the PDGF beta-receptor. The exact mechanism for
      this suppression remains to be clarified.

PMID- 10912789
TI  - Inhibition of PKCalpha and rhoA translocation in differentiated smooth muscle by
      a caveolin scaffolding domain peptide.
AB  - Receptor-coupled contraction of smooth muscle involves recruitment to the plasma
      membrane of downstream effector molecules PKCalpha and rhoA but the mechanism of
      this signal integration is unclear. Caveolins, the principal structural proteins
      of caveolar plasma membrane invaginations, have been implicated in the
      organization and regulation of many signal transducing molecules. Thus, using
      laser scanning confocal immunofluorescent microscopy, we tested the hypothesis
      that caveolin is involved in smooth muscle signaling by investigating caveolin
      isoform expression and localization, together with the effect of a peptide
      inhibitor of caveolin function, in intact differentiated smooth muscle cells. All
      three main caveolin isoforms were identified in uterine, stomach, and ileal
      smooth muscles and assumed a predominantly plasma membranous localization in
      myometrial cells. Cytoplasmic introduction of a peptide corresponding to the
      caveolin-1 scaffolding domain-an essential region for caveolin interaction with
      signaling molecules--significantly inhibited agonist-induced translocation of
      both PKCalpha and rhoA. Translocation was unimpaired by a scrambled peptide and
      was unaltered in sham-treated cells. The membranous localization of caveolins,
      and direct inhibition of receptor-coupled PKCalpha and rhoA translocation by the
      caveolin-1 scaffolding domain, supports the concept that caveolins can regulate
      the integration of extracellular contractile stimuli and downstream intracellular
      effectors in smooth muscle.

PMID- 10912790
TI  - p53 checkpoint-defective cells are sensitive to X rays, but not hypoxia.
AB  - X-ray-induced damage leads to cell-cycle "checkpoint" arrest by p53-dependent
      induction of the cyclin-dependent kinase inhibitor p21 (Waf1/Cip1/Sdi1). Human
      tumor cells that lack this response fail to arrest after exposure to DNA-damaging
      agents, undergo multiple rounds of endoreduplicative DNA synthesis, and
      eventually commit to an apoptotic cell death. Since low oxygen tension can also
      induce p53 protein accumulation, and can lead to cell-cycle arrest or apoptosis,
      we examined the expression of p21 in tumor cells under normoxic and hypoxic
      conditions. In a survey of cells, mRNA for the p21 gene was induced two- to
      threefold in response to hypoxia in a seemingly p53-independent manner. We
      therefore examined genetically matched cells that differ in their p21 and p53
      status for response to ionizing radiation and hypoxia. We found that both p21
      deficient and p53-deficient cells exhibit an increase in chromosome instability,
      an increased level of apoptosis, and a failure to arrest after exposure to
      ionizing radiation. However, cells that lack either p21 or p53 exhibit no
      increase in chromosome instability or elevated apoptosis and still arrest in
      response to hypoxia. Thus, the mechanism responsible for the differential
      response to either hypoxia or X rays presumably lies in the control of cell-cycle
      progression in response to stress and its dependence on p21. Since the loss of a
      DNA-damage-dependent checkpoint does not sensitize cells to killing by stresses
      that elicit a DNA-damage-independent checkpoint, targeting the function of p21
      pharmacologically will not kill tumor cells in situ in the absence of a DNA
      damage signal.

PMID- 10912791
TI  - The central region of Gadd45 is required for its interaction with p21/WAF1.
AB  - Cell cycle arrest represents an important response to genotoxic stress and the
      tumor suppressor p53 has been described to act as a critical effector in this
      biological event. Upon stress, p53 becomes transcriptionally active and up
      regulates the transcription of downstream effector genes, which contain p53
      recognition sites in their regulatory regions. Among the genes activated are p21
      and GADD45, each of which independently exhibits growth-suppressive activity. The
      Gadd45 protein has been described to form a complex with p21, and thus, work was
      undertaken to map the regions of Gadd45 involved in this interaction and to
      examine the roles of those two proteins in growth suppression. In this report, a
      Gadd45 overlapping peptide library and a series of Gadd45 deletion mutants were
      used to define the domains of Gadd45 involved in the association with p21.
      Results using both in vitro and in vivo methods have shown that the interaction
      of Gadd45 with p21 involves a central region of Gadd45. Interestingly, the p21
      binding domain of Gadd45 also encodes the Cdc2-binding activity, indicating that
      the central region of Gadd45 may serve as an important "core," through which
      Gadd45 protein is able to present cross-talk with other cell cycle regulators. In
      addition, GADD45 inhibition of Cdc2 kinase activity was compared with Myd118 and
      CR6, two other members of the GADD45 family. GADD45 was shown to generate the
      strongest inhibitory effect on Cdc2 activity. Finally, results from short-term
      survival assays further demonstrated that p21 and GADD45 act upon different
      cellular pathways to exert their growth-suppressive function.

PMID- 10912792
TI  - p21CIP1 is dispensable for the G2 arrest caused by genistein in human melanoma
      cells.
AB  - We have investigated the effect of genistein on cell cycle distribution of the
      human choroidal melanoma cell line OCM-1. We report that this isoflavonoid
      arrested cells in G2. This effect was correlated with the induction of the CDK
      inhibitor p21CIP1. However, while CDK1 activity was markedly reduced following
      genistein treatment, CDK2 activity was not affected. This was in agreement with
      the absence of G1 arrest that we observed but caused some doubt about the
      functionality of p21CIP1. Attempts to demonstrate mutation or post-translational
      modification of p21CIP1 from OCM-1 cells were unsuccessful. In fact, the level of
      p21CIP1 induced by genistein was shown to be insufficient to cause CDK2
      inhibition. The role of p21CIP1 in the inhibition of CDK1 was questionable, as we
      demonstrated that genistein impaired Tyr15 dephosphorylation of CDK1 and because
      CDK1-cyclin B1 complexes from treated cells could be reactivated upon exposure to
      CDC25 phosphatase. Finally, we report that p21CIP1 was not absolutely required
      for the genistein-induced G2 arrest, as the isoflavone caused at least partial G2
      arrest in p21-deficient Rat-1 fibroblasts as well as in p21-/- mouse embryo
      fibroblasts.

PMID- 10912793
TI  - Activation of mitogen-activated protein kinases is required for alpha1-adrenergic
      agonist-induced cell scattering in transfected HepG2 cells.
AB  - Activation of alpha1B-adrenergic receptors ((alpha1B)AR) by phenylephrine (PE)
      induces scattering of HepG2 cells stably transfected with the (alpha1B)AR (TFG2
      cells). Scattering was also observed after stimulation of TFG2 cells with phorbol
      myristate acetate (PMA) but not with hepatocyte growth factor/scatter factor,
      epidermal growth factor, or insulin. PMA but not phenylephrine rapidly activated
      PKCalpha in TFG2 cells, and the highly selective PKC inhibitor
      bisindolylmaleimide (GFX) completely abolished PMA-induced but not PE-induced
      scattering. PE rapidly activated p44/42 mitogen-activated protein kinase (MAPK),
      p38 MAPK, c-Jun N-terminal kinase (JNK), and AP1 (c-fos/c-jun). Selective
      blockade of p42/44 MAPK activity by PD98059 or by transfection of a MEK1 dominant
      negative adenovirus significantly inhibited the PE-induced scattering of TFG2
      cells. Selective inhibition of p38 MAPK by SB203850 or SB202190 also blocked PE
      induced scattering, whereas treatment of TFG2 cells with the PI3 kinase
      inhibitors LY294002 or wortmannin did not inhibit PE-induced scattering. Blocking
      JNK activation with a dominant negative mutant of JNK or blocking AP1 activation
      with a dominant negative mutant of c-jun (TAM67) significantly inhibited PE
      induced cell scattering. These data indicate that PE-induced scattering of TFG2
      cells is mediated by complex mechanisms, including activation of p42/44 MAPK, p38
      MAPK, and JNK. Cell spreading has been reported to play important roles in wound
      repair, tumor invasion, and metastasis. Therefore, catecholamines acting via the
      (alpha1)AR may modulate these physiological and pathological processes.

PMID- 10912794
TI  - Predominant intracellular localization of the type I transforming growth factor
      beta receptor and increased nuclear accumulation after growth arrest.
AB  - Transforming growth factor-beta (TGF-beta) signaling requires the functional
      interaction of two distinct receptors, type I (RI) and type II (RII), at the cell
      surface. Exposure of cells to TGF-beta results in receptor internalization and
      down-regulation (Zwaagstra et al., 1999, Exp. Cell Res. 252, 352362); however,
      little is known about the subsequent fate of RI or RII. In this study the
      cellular distribution of RI was examined in cells before and after treatment with
      ligand. RI was localized by immunocytochemistry and confocal microscopy using two
      polyclonal antisera directed against two different epitopes, one in the C
      terminal region and one in the N-terminal region of the cytoplasmic domain. The
      majority of RI molecules in untreated MvlLu and A549 cells were found to be
      intracellular. Treatment of MvlLu and A549 cells with 100 pM TGF-beta1 for 24 h
      at 37 degrees C caused a redistribution of surface RI on MvlLu cells, as
      evidenced by surface RI aggregation. Unexpectedly, this TGF-beta1 treatment also
      caused redistribution and accumulation of intracellular RI in and around the
      nucleus for both MvlLu and A549 cells. Nuclear accumulation of RI was also
      promoted independently of ligand receptor activation by treatment of MvlLu cells
      with olomoucine, an agent that results in growth arrest. The capacity of RI to
      localize in the nucleus was confirmed by microscopic examination of 293 cells
      transiently expressing RI fused to green fluorescent protein (RI-GFP). Olomoucine
      treatment of these cells resulted in the movement of RI-GFP into the nucleus. Our
      results indicate that growth arrest alters intracellular transport/routing of RI
      and may indicate that RI functions not only at the cell surface but inside the
      cell as well.

PMID- 10912795
TI  - Independent role of p38 and ERK1/2 mitogen-activated kinases in the upregulation
      of matrix metalloproteinase-1.
AB  - Matrix metalloproteinase-1 (MMP-1) plays an important role in the degradation of
      extracellular matrix components under several physiological and pathological
      conditions. The expression of this protease is upregulated by mitogenic growth
      factors and proinflammatory cytokines, which have been shown to activate
      different sets of mitogen-activated protein (MAP) kinase pathways. Here we
      provide evidence that activation of the extracellular signal-regulated kinase 1/2
      (ERK1/2) or the p38 MAP kinase pathway is sufficient to induce transcription from
      the MMP-1 promoter in human primary fibroblasts, whereas modulation of mRNA
      stability seems to be of minor importance. Upregulation of MMP-1 expression by
      mitogenic or inflammatory stimuli is blocked by specific small molecular weight
      inhibitors of the ERK pathway or the p38 pathway, respectively, and
      constitutively active kinases within the ERK1/2 pathway (MEKK1, MEK1) or the p38
      pathway (ASK1, MEKK1, MKK3) are potent activators of the MMP-1 promoter. The
      current study provides evidence that distinct extracellular signals leading to
      upregulation of MMP-1 expression in fibroblasts are relayed independently through
      different MAP kinase pathways and are integrated at the level of the promoter.

PMID- 10912796
TI  - The Xenopus laevis aurora/Ip11p-related kinase pEg2 participates in the stability
      of the bipolar mitotic spindle.
AB  - The Xenopus laevis aurora/Ip11p-related kinase pEg2 is required for centrosome
      separation, which is a prerequisite for bipolar mitotic spindle formation. Here,
      we report that the inhibition of pEg2 by addition of either an inactive kinase or
      a monoclonal antibody destabilizes bipolar spindles previously assembled in
      Xenopus egg extracts. The bipolar spindles collapse to form structures such as
      microtubule asters with chromosome rosettes, monopolar spindles, and multipolar
      spindles. In collapsed spindles, chromosomes remain attached to the microtubules
      plus ends. The destabilization of the bipolar spindle is reminiscent of the
      destabilization observed after inhibition of cross-linking activities which
      maintain parallel and anti-parallel microtubules linked together. We have
      previously reported that pEg2 phosphorylates the kinesin-related protein XlEg5
      which is involved in centrosome separation but which was also reported to be
      involved in spindle stability. The collapse of the bipolar spindle observed after
      inhibition of pEg2 suggests that the kinase might regulate the cross-linking
      activity of XlEg5. We do not exclude the possibility that pEg2 also regulates
      other microtubule-based motor proteins involved in bipolar spindle stability. To
      our knowledge, this is the first evidence that aurora/Ip11p-related kinase
      activity actually participates not only in mitotic spindle formation by
      regulating centrosome separation but also in mitotic spindle stabilization.

PMID- 10912797
TI  - Form of human p53 protein during nuclear transport in Xenopus laevis embryos.
AB  - The p53 protein binds DNA as a tetramer inside the nucleus, but a form of the p53
      protein during nuclear transport has not been fully elucidated. To verify whether
      the human p53 protein passes through the nuclear pore as a monomer or oligomer,
      two different p53 mutants N1 and C1NLS- with or without a nuclear localization
      signal (NLS), respectively, were expressed in Xenopus laevis embryos. By the
      whole-mount immunostaining method, their intracellular distributions were
      observed to exist in an NLS-dependent manner. In a immunoprecipitation assay
      system, NLS-defective mutants formed oligomer in the cytoplasm. When coexpressed
      with NLS-containing N1, C1NLS- still stayed in the cytoplasm and did not inhibit
      N1 transport into the nucleus. Furthermore, when oligomerization-defective p53
      mutant was expressed in Xenopus embryos, efficiency of its nuclear transport was
      demonstrated to be unchanged compared to that of the wild type. Assuming that NLS
      defective p53 mutants have no dominant-negative effect on wild-type p53 in the
      nucleus of p53 heterozygous cells, we investigated the dominant-negative effect
      by CAT activity assay using human cell line Saos-2 and NLS-defective mutants. It
      was found that the NLS-defective p53 mutant did not have a dominant-negative
      effect on the function of wild-type p53 protein in the nucleus. Data indicate
      that each monomeric p53 protein independently passes through the nuclear pore;
      however, the possibility of homooligomeric p53 protein transport into the nucleus
      is not completely excluded.

PMID- 10912798
TI  - Immunocytochemical and biochemical characterization of FMRP, FXR1P, and FXR2P in
      the mouse.
AB  - Fragile X syndrome is caused by the absence of expression of the FMR1 gene. Both
      FXR1 and FXR2 are autosomal gene homologues of FMR1. The products of the three
      genes are belonging to a family of RNA-binding proteins, called FMRP, FXR1P, and
      FXR2P, respectively, and are associated with polyribosomes as cytoplasmic mRNP
      particles. The aim of the present study is to obtain more knowledge about the
      cellular function of the three proteins (Fxr proteins) and their
      interrelationships in vivo. We have utilized monospecific antibodies raised
      against each of these proteins and performed Western blotting and immunolabeling
      at the light-microscopic level on tissues of wild-type and Fmr1 knockout adult
      mice. In addition, we have performed immunoelectron microscopy on hippocampal
      neurons of wild-type mice to study the subcellular distribution of the Fxr
      proteins. A high expression was found in brain and gonads for all three proteins.
      Skeletal muscle tissue showed only a high expression for Fxr1p. In the brain the
      three proteins were colocalized in the cytoplasm of the neurons; however, in
      specific neurons Fxr1p was also found in the nucleolus. Immunoelectronmicrsocopy
      on hippocampal neurons demonstrated the majority of the three proteins in
      association with ribosomes and a minority in the nucleus. The colocalization of
      the Fxr proteins in neurons is consistent with similar cellular functions in
      those specific cells. The presence of the three proteins in the nucleus of
      hippocampal neurons suggests a nucleocytoplasmic shuttling for the Fxr proteins.
      In maturing and adult testis a differential expression was observed for the three
      proteins in the spermatogenic cells. The similarities and differences between the
      distribution of the Fxr proteins have implications with respect to their normal
      function and the pathogenesis of the fragile X syndrome.

PMID- 10912799
TI  - Purification and characterization of beta-actin-rich tumor cell pseudopodia: role
      of glycolysis.
AB  - The MSV-MDCK-INV invasive variant of Moloney sarcoma virus (mos) transformed MDCK
      cells express multiple beta-actin-rich pseudopodia (P. U. Le et al., Cancer Res.
      58, 1631-1635, 1998). We show here that the tips of these actively protruding
      cellular domains are morphologically distinct presenting numerous blebs and
      selectively pass through 1-microm-pore filters. The pseudopodia were purified
      from the underside of the filters and a major protein component was identified as
      the glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). By
      confocal microscopy, GAPDH colocalized with actin in MSV-MDCK-INV pseudopodia
      localizing this glycolytic enzyme to this site of active actin polymerization.
      Inhibition of glycolysis with 2-deoxyglucose or oxamate induced a rapid
      transformation of beta-actin-rich pseudopodia into extended lamellipodia and
      prevented cell motility. A localized glycolytic supply of energy therefore
      regulates the formation of beta-actin-rich pseudopodial protrusions and thereby
      the motility of invasive tumor cells.

PMID- 10912800
TI  - Apical secretion and sialylation of soluble dipeptidyl peptidase IV are two
      related events.
AB  - The role of glycans in the apical targeting of proteins in epithelial cells
      remains a debated question. We have expressed the mouse soluble dipeptidyl
      peptidase IV (DPP IV ectodomain) in kidney (MDCK) and in intestinal (Caco-2)
      epithelial cell lines, as a model to study the role of glycosylation in apical
      targeting. The mouse DPP IV ectodomain was secreted mainly into the apical medium
      by MDCK cells. Exposure of MDCK cells to GalNac-alpha-O-benzyl, a drug previously
      described as an inhibitor of mucin O-glycosylation, produced a protein with a
      lower molecular weight. In addition this treatment resulted in a decreased apical
      secretion and an increased basolateral secretion of mouse DPP IV ectodomain. When
      expressed in Caco-2 cells, the mouse DPP IV ectodomain was secreted mainly into
      the basolateral medium. However, BGN was still able to decrease the amount of
      apically secreted protein and to increase its basolateral secretion.
      Neuraminidase digestion showed that the most striking effect of BGN was a
      blockade of DPP IV sialylation in both MDCK and Caco-2 cells. These results
      indicate that a specific glycosylation step, namely, sialylation, plays a key
      role in the control of the apical targeting of a secreted DPP IV both in MDCK and
      Caco-2 cells.

PMID- 10912801
TI  - Different functional recognition of basolateral signals in Caco-2 and MDCK cells.
AB  - Using the basolateral mutant PS of the normally apical neurotrophin receptor p75
      (p75NTR) we have identified two cytoplasmic determinants responsible for this
      reversed localization in the human intestinal cell line, Caco2. These signals are
      based on two consecutive leucines (322-323) and a tyrosine (Y308). Truncation of
      the cytoplasmic tail removing the two leucines or their replacement by alanines
      led to a nonpolarized expression of the resulting mutants in Caco2 cells. To our
      surprise, the same mutations had no effect on the basolateral localization of the
      mutant PS in MDCK cells. In MDCK cells, the basolateral localization was entirely
      dependent on a cytoplasmic tyrosine Y308, while in Caco-2 cells this tyrosine
      signal was functional as a basolateral signal only when the cytoplasmic domain of
      PS was truncated shortly after it. These data indicate for the first time that
      there is a differential recognition of basolateral signals between MDCK and Caco
      2 cells.

PMID- 10912803
TI  - Simian virus 40 induces multiple S phases with the majority of viral DNA
      replication in the G2 and second S phase in CV-1 cells.
AB  - The infection of permissive monkey kidney cells (CV-1) with simian virus 40
      induces G1 growth-arrested cells into the cell cycle. After completion of the
      first S phase and movement into G2, mitosis was blocked and the cells entered
      another DNA synthesis cycle (second S phase). Growth-arrested CV-1 cells
      replicated significant amounts of viral DNA in the G2 phase with the majority of
      synthesis occurring during the second S phase. When mimosine-blocked (G1/S)
      infected cells were released into the cell cycle, a major portion of the viral
      DNA was detected in G2 with the largest accumulation in the second S phase. The
      total DNA produced per infected cell was 10-12C with approximately 0.5-2C of
      viral DNA replicated per cell. Therefore the majority of the DNA per cell was
      cellular, 4C from the first S phase and approximately 4-6C from the second
      cellular synthesis phase.

PMID- 10912802
TI  - Analysis of the subcellular distribution of protein kinase Calpha using PKC-GFP
      fusion proteins.
AB  - One important factor for the determination of the specific functions of protein
      kinase C (PKC) isoforms is their specific subcellular localization. In NIH 3T3
      fibroblasts phorbol esters induce translocation of PKCalpha to the plasma
      membrane and the nucleus. In order to investigate PKCalpha's subcellular
      distribution and especially its nuclear accumulation in more detail we used
      fusion proteins consisting of PKCalpha and the green fluorescent protein (GFP).
      Purified GFP-PKCalpha from baculovirus-infected insect cells undergoes nuclear
      accumulation without any further stimuli in digitonin-permeabilized cells.
      Interestingly, permeabilization appears to be a trigger for PKCalpha's nuclear
      translocation, since the fusion protein also translocates to the nucleus in
      transiently transfected cells following permeabilization. This suggests that
      PKCalpha has a high nuclear binding capacity even in the case of large protein
      amounts. In contrast to endogenous PKCalpha, overexpressed GFP-PKCalpha as well
      as overexpressed PKCalpha itself translocates mainly to the plasma membrane and
      only to a smaller extent to the nucleus following stimulation with phorbol ester.
      Use of fusion proteins of GFP and different mutants of PKCalpha enabled
      determination of motifs involved PKCalpha's subcellular distribution: A25E and
      K368R point mutations of PKCalpha showed enhanced affinity for the plasma
      membrane, whereas sequences within the regulatory domain probably confer
      PKCalpha's nuclear accumulation.

PMID- 10912804
TI  - Doxorubicin treatment activates a Z-VAD-sensitive caspase, which causes deltapsim
      loss, caspase-9 activity, and apoptosis in Jurkat cells.
AB  - Doxorubicin induces caspase-3 activation and apoptosis in Jurkat cells but
      inhibition of this enzyme did not prevent cell death, suggesting that another
      caspase(s) is critically implicated. Western blot analysis of cell extracts
      indicated that caspases 2, 3, 4, 6, 7, 8, 9, and 10 were activated by
      doxorubicin. Cotreatment of cells with the caspase inhibitors Ac-DEVD-CHO, Z
      VDVAD-fmk, Z-IETD-fmk, and Z-LEHD-fmk alone or in combination, or overexpression
      of CrmA, prevented many morphological features of apoptosis but not loss of
      mitochondrial membrane potential (delta(psi)m), phospatidilserine exposure, and
      cell death. Western blot analysis of cells treated with doxorubicin in the
      presence of inhibitors allowed elucidation of the sequential order of caspase
      activation. Z-IETD-fmk or Z-LEHD-fmk, which inhibit caspase-9 activity, blocked
      the activation of all caspases studied, lamin B degradation, and the development
      of apoptotic morphology, but not cell death. All morphological and biochemical
      features of apoptosis, as well as cell death, were prevented by cotreatment of
      cells with the general caspase inhibitor Z-VAD-fmk or by overexpression of Bcl-2.
      Doxorubicin cytotoxicity was also blocked by the protein synthesis inhibitor
      cycloheximide. Delayed addition of Z-VAD-fmk after doxorubicin treatment, but
      prior to the appearance of cells displaying a low delta(psi)m, prevented cell
      death. These results, taken together, suggest that the key mediator of
      doxorubicin-induced apoptosis in Jurkat cells may be an inducible, Z-VAD
      sensitive caspase (caspase-X), which would cause delta(psi)m loss, release of
      apoptogenic factors from mitochondria, and cell death.

PMID- 10912823
TI  - Kinematic properties of rapid hand movements in a knob turning task.
AB  - In order to understand how the central nervous system controls the kinematics of
      rapid finger and hand movements, we studied the motions of subjects turning a
      knob to light-emitting diode targets, similar to tuning a radio dial. On many
      trials, subjects turned the knob with a single, smooth, and regular motion as
      revealed by the angular position and velocity trajectories, but on others,
      subjects produced irregularities in the kinematics. Like many past studies, we
      interpreted these irregularities as discrete corrective submovements. Unlike
      other studies, we used a direct, objective algorithm to identify overlapping
      submovements, detecting appreciable inflections in the acceleration traces by
      examining zero crossings in their derivatives, jerk and snap. The movements
      without overlapping submovements on average had a near symmetric, bell-shaped
      velocity profile that was independent of speed, and which matched the theoretical
      minimum jerk velocity very closely. We proposed three plausible mechanisms for
      altering the shape of movement kinematics, and implemented a mass-spring model
      with nonlinear damping to explore the possibilities. Although there was
      relatively little variability in the shape and symmetry of movements across
      trials, there was a fair amount of variability in their amplitude. We show that
      subjects attempted to eliminate the need for corrective submovements by making
      more accurate primary movements with practice, but that the variability inherent
      in rapid movements dictated the need for corrective submovements. Subjects used
      corrective submovements to improve final endpoint accuracy while reducing
      endpoint variability, resulting in higher task success rates.

PMID- 10912824
TI  - The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in
      the rat.
AB  - Horizontal and vertical eye movements were recorded in alert pigmented rats using
      chronically implanted scleral search coils or temporary glue-on coils to test the
      dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body
      orientation. The contributions of semicircular-canal versus otolith-organ signals
      to the VOR were investigated by providing canal-only (vertical axis) and canal
      plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated
      canals only (upright yaw and nose-up roll) produced an accurate VOR during middle
      and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz,
      the canal-only rotations elicited a phase-advanced VOR. The addition of a
      changing gravity stimulus, and thus dynamic otolith stimulation, to the canal
      signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with
      accurate phase down to the lowest frequency tested (0.02 Hz). In order to further
      test the dependence of the VOR on gravitational signals, we tested vertical VOR
      with the head in an inverted posture (inverted roll). The VOR in this condition
      was advanced in phase across all frequencies tested. At low frequencies, the VOR
      during inverted roll was anticompensatory, characterized by slow-phase eye
      movement in the same direction as head movement. The substantial differences
      between canalonly VOR and canal plus otolith VOR suggest an important role of
      otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests
      that part of the otolith contribution arises from static tilt signals that are
      inverted when the head is inverted.

PMID- 10912825
TI  - Identification and localisation of auditory areas in guinea pig cortex.
AB  - The organisation of guinea pig auditory cortex was studied by combining
      histological methods with microelectrode mapping. This allowed the location of
      seven auditory areas to be determined in relation to the visual and primary
      somatosensory areas. The auditory areas were identified by single-unit recordings
      and their borders defined by evoked potential mapping. The visual areas were
      identified by their relatively high densities of myelinated fibres, while the
      primary somatosensory cortex was identified by its characteristic barrels of high
      cytochrome oxidase (CYO) activity in layer IV. The auditory region had moderate
      levels of CYO and myelin staining. When staining was optimal, there was a clear
      edge to the moderate CYO activity, which apparently corresponds to the dorsal
      border of the primary auditory area (AI) and the other core field that lies
      dorsocaudal to it (DC). Thus the primary somatosensory area and the visual and
      auditory regions were separated from each other by a region with lower levels of
      CYO and myelin staining. The ventral borders of AI and DC could not be determined
      histologically as there were no sharp transitions in the levels of CYO or myelin
      staining. The two core areas were partially surrounded by belt areas. The
      dorsorostral belt and most of the belt around DC responded more strongly to broad
      band stimuli than pure tones, while the ventrorostral belt, small field and a
      belt zone ventral to the rostral part of DC responded better to pure tones. Units
      in the small field (S) typically had higher thresholds and broader tuning to pure
      tones than AI, while units in the ventrorostral belt typically had longer onset
      latencies and gave more sustained responses than units in AI.

PMID- 10912826
TI  - Altered visuo-motor behavior during inactivation of the caudal fastigial nucleus
      in the cat.
AB  - It is known that the medio-posterior cerebellar lobules VI/VII of the vermis and
      caudal part of the fastigial nucleus (cFN) are involved in the control of
      saccadic displacements of the visual axis in space (gaze). We have recently shown
      in the head-unrestrained cat that inactivation of the cFN severely impairs the
      accuracy of orienting gaze shifts toward visual targets by altering the amplitude
      of both eye and head components. In the present paper, we report additional data
      that indicate that the deficits induced by cFN inactivation are not restricted to
      saccadic gaze shifts but extend to the forward reaching movement of the whole
      body toward a visual target. Indeed, the path followed by the animal walking
      toward a visible food target was systematically curved toward the inactivated
      side. This deficit could largely be accounted for by an angular bias in the
      heading direction used by the animal to reach the target. These data suggest that
      pharmacological inactivation of the cFN leads to a general deficit in spatial
      orientation.

PMID- 10912827
TI  - Lack of growth-associated protein-43 reemergence or of growth-associated protein
      43 mRNA modulation in deafferented vestibular nuclei during the first 6 weeks
      after unilateral inner ear lesion.
AB  - We investigated whether a unilateral inner ear lesion that destroyed the
      labyrinthine receptors, the cochlear receptors, and the spiral ganglion induced
      collateral sprouting in rat vestibular and auditory brainstem nuclei, using
      growth-associated protein-43 (GAP-43) as an indicator of synaptic remodeling.
      Both immunocytochemistry and in situ hybridization were performed to detect a
      potential modulation of GAP-43 and of its messenger RNA (mRNA) at different times
      after surgery. We failed to observe a reemergence of GAP-43 or a modulation of
      its mRNA in the deafferented vestibular nuclei at all survival times tested. In
      contrast, a substantial increase in the expression of GAP-43 was observed in the
      neuropil of the ipsilateral deafferented cochlear nuclei and in cell bodies of
      the ipsilateral superior olive. This increase was associated with an up- and
      downregulation of the mRNA coding for GAP-43 in the ipsilateral ventral cochlear
      nucleus and in the ipsilateral superior olive, respectively. These data indicate
      that synaptic remodeling, as assessed by GAP-43 expression, does not seem to
      occur in the deafferented vestibular complex during the first 6 weeks after
      labyrinthectomy, whereas it occurs within the first deafferented auditory relays
      at times as early as 4 days following spiral ganglion and cochlear receptors
      removal. We conclude that recovery of a normal resting discharge of the
      deafferented central vestibular neurons and consequently recovery of a normal
      resting posture and eye position may not depend on collateral sprouting of the
      remaining vestibular afferents. In contrast, we confirmed that a reactive
      synaptogenesis occurs in the brainstem auditory nuclei following cochlea and
      spiral ganglion removal. Its functional significance remains an open question.

PMID- 10912828
TI  - An immunohistochemical study of neuronal and glial cell reactions in retinae of
      rats with experimental glaucoma.
AB  - Glaucoma is a common disease seen in the eye clinic, but its associated
      pathological processes, especially the role of glial cells in glaucomatous
      retinae, are still under debate. The aim of the present work was to study the
      responses of astrocytes, Muller cells and microglia in retinae of rats with
      experimental glaucoma. Glaucoma was induced in adult male Wistar rats by
      cauterizing limbal-derived veins and the changes in glial fibrillary acidic
      protein (GFAP), OX42, OX18, OX6 and EDI expression were studied by
      immunohistochemical staining. Neuronal cell viability was studied by
      immunostaining with the neuronal nuclei (NeuN) antibody. In the experimental
      glaucomatous eyes, a significant drop in the number of NeuN-positive neurons was
      observed from 7 days postoperation and beyond in both the ganglion cell layer and
      inner nuclear layer. The expression of GFAP and OX42 was increased during the
      first 2 months after operation and reduced in rats at 3 and 4 months. OX6 and
      OX18 immunoreactivity was induced in some microglia of both glaucomatous and sham
      operated control eyes. Possible mechanisms of the reaction of astrocytes, Muller
      cells and microglia in neuronal degeneration following glaucoma are discussed.

PMID- 10912829
TI  - Electromyographic responses to a mechanical perturbation applied during impending
      arm movements in different directions: one-joint and two-joint conditions.
AB  - Directional tuning is a common finding for many physiological features of arm
      movements and related neuronal activity. We investigated whether the
      electromyographic response to a brief (30 ms) torque perturbation prior to
      voluntary movement depends on the direction of the impending movement. Pointing
      movements with the elbow joint alone and those involving both the shoulder and
      elbow joints were studied in separate experiments. Target direction was varied
      between flexion and extension for the one-joint experiments and among four
      spatial directions for the two-joint experiments. Movement trials in which a
      perturbation stretched the flexor muscles just prior to the pointing movement
      were randomly interspersed among unperturbed movement trials in each experiment.
      A small pre-load ensured some background activity of the flexor muscles. Results
      were remarkably similar for the one- and two-joint conditions. The short-latency
      reflex response of the stretched muscles (in a 30-60 ms window after perturbation
      onset) was not modulated with direction of target-reaching movement in a
      statistically significant manner, which confirms earlier findings for one-joint
      movements and extends these to the two-joint condition. Beyond the short-latency
      window, the perturbation provoked earlier onsets of target-reaching muscle
      activities for the agonist muscles, whether or not the muscle had been stretched
      by the perturbation. The onset of the braking activity of the antagonist muscles
      also occurred earlier in the presence of the brief perturbation prior to
      movement, irrespective of whether the muscle had been stretched or not. The
      magnitude of target-reaching muscle activity, in general, was greater for the
      perturbed trials, though not consistently for all muscles or all directions.
      These results suggest that, when movement is about to be initiated, in either
      single- or multi-joint conditions, the long-latency effects of the stretch
      strongly depend on the intended direction of movement. The dependence is such
      that the response serves to hasten and augment the intended movement, but not
      necessarily to oppose the perturbation.

PMID- 10912830
TI  - Effects of lingual nerve afferents on swallowing in sheep.
AB  - We investigated in sheep the effects of stimulation of the thick afferent fibers
      running through the lingual nerve (LN) upon the activity of some of the muscles
      and medullary interneurons or motoneurons which are active during swallowing.
      Using electromyography (EMG), and extra- and intracellular neuronal recording, we
      demonstrated that LN stimulation inhibited triggering and/or distal progression
      of deglutition reflexly induced by stimulation of the superior laryngeal nerve
      (SLN). This inhibition appeared as a delay, or the interruption or total
      suppression, of the EMG and neuronal swallowing activities, depending on the
      interval between SLN and LN stimulation. It was apparent at the level of the
      muscles and motoneurons of the nucleus ambiguus, as well as at the level of the
      interneurons of the dorsal medulla within or around the nucleus of solitary
      tract, which are assumed to be the core of the organizing system for swallowing,
      the so-called central pattern generator (CPG). Taking into account the
      stimulation parameters used in our experiments, it was likely that only LN
      mechanosensitive fibers were excited. These fibers were involved in the jaw
      opening reflex, and possibly in mastication regulation. Therefore, inhibition of
      swallowing could result from interactions between the hindbrain mastication and
      swallowing CPGs. However, it was also possible that mechanosensitive afferents
      acted upon the swallowing CPG directly or indirectly through supramedullary,
      especially cortical, loops.

PMID- 10912831
TI  - Changes in glutathione in the hippocampus of rats injected with kainate:
      depletion in neurons and upregulation in glia.
AB  - The aim of the present study was to elucidate the distribution of glutathione
      immunoreactivity in the normal hippocampus and after kainate-induced neuronal
      injury. A specific antibody was used that recognizes both the reduced (GSH) and
      oxidized (GSSG) forms of glutathione. Immunoreactivity to glutathione was
      observed in neurons, but few immunolabeled glial cells were observed in the
      normal hippocampus. After kainate injection, a decrease in glutathione
      immunoreactivity was observed in pyramidal neurons from as early as 1 day after
      injection. In contrast, dense staining to glutathione was observed in large
      numbers of reactive astrocytes at 3 days to 6 weeks after kainate injection. This
      suggests upregulation of glutathione synthesis in these cells. One possibility is
      that the high content of glutathione is protective to reactive astrocytes.
      Another possibility is that the high glutathione concentration in reactive
      astrocytes may be protective to neurons around the glial scar.

PMID- 10912832
TI  - Post-exercise facilitation of compound muscle action potentials evoked by
      transcranial magnetic stimulation in healthy subjects.
AB  - Post-exercise facilitation (PEF) of motor evoked potentials (MEPs) was studied by
      transcranial magnetic stimulation in 15 healthy subjects following standardized
      and controlled isometric contraction of the biceps brachii muscle. PEF was highly
      dependent on the time delay (TD) from muscle relaxation to delivery of the
      magnetic stimulus and only to a minor degree on the duration of the maintained
      muscular contraction of 2, 4, and 6 s. In addition, PEF was unaffected by the
      contraction levels of 25%, 50%, and 100% of maximal voluntary contraction (MVC).
      There was a linear relationship between the log amplitude of the post-exercise
      MEPs and the TD. The time point at which PEF had vanished was calculated to be
      15.2 s. In order to challenge the question whether segmental and/or
      suprasegmental mechanisms are primarily responsible for PEF, MEPs and H-reflexes
      were recorded from the soleus muscle following a sustained plantar flexion at the
      ankle joint in three healthy subjects. PEF of MEPs was present at a TD of 1000 ms
      following a sustained contraction of 6 s at a level of 50% of MVC. It was
      accompanied by a pronounced decrease in the soleus H-reflex amplitude at a TD of
      1000 ms.

PMID- 10912833
TI  - Differences between motion-direction perception and unspecific motion perception
      in the human knee joint.
AB  - Perception has commonly been seen as a conscious performance. Thus, regarding
      proprioception in some publications, it has been proposed that the term is
      properly used only when subjects are able to report on the direction as well as
      presence of imposed movements. Consequently, detections of movements without
      movement-direction perception have not been accepted as perceived, since these
      detections were regarded as unspecific. Unspecific sensation has been suggested
      to precede perception. From this "two-state model", it follows that threshold
      values should be lower for unconscious unspecific perception than for conscious
      specific perception. The aim of the present study was to test this suggested
      dichotomy. Proprioception was compared in unspecific detection trials (only the
      occurrence of a movement had to be detected, not its direction) and direction
      specific detection trials (the occurrence of a movement of a specific direction
      had to be detected). Two types of specific detection trials and two types of
      unspecific detection trials were studied. Pairs of threshold values were
      determined, regarding amplitude detection using different angular velocities and
      regarding velocity detection using different angular displacements, for flexion
      and extension. Our results showed that, independent of each other, both threshold
      paradigms (amplitude detection and velocity detection) revealed the same
      perception characteristics. In specific detection paradigms, the proprioceptive
      thresholds were two times lower than in unspecific detection paradigms. Thus,
      movements of a particular type could be detected more easily than movement per
      se. The suggested "two-state model" might, therefore, not be appropriate in
      describing proprioceptive perception.

PMID- 10912834
TI  - The spatial distribution of visual attention in developmental dyslexia.
AB  - The present study investigated the spatial distribution of visual attention in
      dyslexic and normally reading children. The performances of the two groups were
      investigated using two different paradigms. In experiment 1 we analyzed the
      distribution of processing resources both inside and outside the focus of visual
      attention by simply recording reaction times to the detection of a white dot
      target projected at different eccentricities from the fovea. The distribution of
      attentional resources differed significantly between the two groups of children.
      The eccentricity of the stimulus was significant only for normally reading
      children - who showed a normal gradient - as it influenced their detection speed,
      whereas it had no effect on dyslexic children, who exhibited a diffused
      distribution of visual processing resources inside the visual field. In
      experiment 2 we studied the distributed (unfocused) mode of attention in a visual
      search task by measuring reaction times to a target stimulus inside a large
      configuration with a variable number of distractors. Results show that as
      compared to normal children dyslexics are better able to distribute their
      attentional resources diffusely. Our conclusion is that reading disability may be
      characterized by a diffused distribution of visual processing resources. These
      data might be interpreted in the framework of studies on magnocellular deficits
      in dyslexia, whereby the anomalous distribution of visual attention might explain
      how transient pathway functioning influences the reading process.

PMID- 10912836
TI  - The relation between movement parameters and motor learning.
AB  - In a recent paper, Flament et al. (1999) studied the process of learning to flex
      the elbow faster. They concluded from their data that time-related parameters
      (e.g. movement time) changed faster during learning than magnitude-related
      parameters (e.g. peak velocity) and discussed this finding in terms of neural
      substrates responsible for the apparently different learning mechanisms. In this
      paper, I will argue that finding different time constants does not imply
      different learning mechanisms and will give a theoretical example of the
      development of parameters during learning to move faster. Despite the fact that
      only one learning process is modelled, various kinematic parameters show
      different time courses of learning. The differences the model predicts are
      comparable with the experimental results.

PMID- 10912835
TI  - Low-frequency otolith and semicircular canal interactions after canal
      inactivation.
AB  - During sustained constant velocity and low-frequency off-vertical axis rotations
      (OVAR), otolith signals contribute significantly to slow-phase eye velocity. The
      adaptive plasticity of these responses was investigated here after semicircular
      canal plugging. Inactivation of semicircular canals results in a highly
      compromised and deficient vestibulo-ocular reflex (VOR). Based on the VOR
      enhancement hypothesis, one could expect an adaptive increase of otolith-borne
      angular velocity signals due to combined otolith/canal inputs after inactivation
      of the semicircular canals. Contrary to expectations, however, the steady-state
      slow-phase velocity during constant velocity OVAR decreased in amplitude over
      time. A similar progressive decrease in VOR gain was also observed during low
      frequency off-vertical axis oscillations. This response deterioration was present
      in animals with either lateral or vertical semicircular canals inactivated and
      was limited to the plane(s) of the plugged canals. The results are consistent
      with the idea that the low-frequency otolith signals do not simply enhance VOR
      responses. Rather, the nervous system appears to correlate vestibular sensory
      information from the otoliths and the semicircular canals to generate an integral
      response to head motion.

PMID- 10912837
TI  - Costs induced by hip fractures: a prospective controlled study in Belgium.
      Belgian Hip Fracture Study Group.
AB  - The economic burden of hip fractures is thought to be important, but the excess
      medical costs they induce remain largely unknown. We assessed the direct medical
      costs induced by hip fractures during and after hospitalization. Hospital costs
      of 170 consecutive Belgian women with hip fracture were gathered. During the year
      following discharge, all medical costs were collected for the 159 hip fracture
      women who survived the acute hospitalization stay. A similar collection of data
      was performed on a comparison group of 159 age-and residence-matched women
      without a history of hip fracture. The mean cost of the acute hospital stay was
      8,667 Belgian francs and the mean 1-year hip-fracture-related extra costs after
      hospitalization was 6,636 Belgian francs. During the year following the acute
      hospital stay, 19% of the hip fracture women and 4% of the comparison women were
      newly admitted to nursing homes (p<0.001). Although health care costs increased
      with age, hip-fracture-related extra costs after hospitalization seemed similar
      in those below or above 81 years old. These extra costs amounted to 7,710 Belgian
      francs in women not living in nursing homes at the time of fracture, and to 3,479
      Belgian francs in women who lived in nursing homes. Health or mental status
      before hip fracture seemed not to affect extra costs. Taking into account the
      higher mortality of women with hip fracture, the extra costs during the acute
      hospital stay and during the 1-year follow-up amounted to a mean 15,151 Belgian
      francs. In conclusion, both acute hospital stays and subsequent medical care
      contribute significantly to medical costs induced by hip fractures.

PMID- 10912838
TI  - Walking after stroke: does it matter? Changes in bone mineral density within the
      first 12 months after stroke. A longitudinal study.
AB  - Stroke patients have increased risk of hip fractures. Nearly all fractures occur
      on the hemiplegic side, and reduced bone mineral density (BMD) may be an
      important predisposing factor. The aim of this study was to investigate the
      degree of demineralization within the first year after stroke, and to elucidate a
      possible difference in patients with high versus low ambulatory levels. Forty
      acute stroke patients were followed (17 initially wheelchair-bound and 23
      initially ambulatory). BMD was measured in the proximal femur bilaterally at a
      mean 6 days, 7 months and 1 year after stroke onset using dual-energy X-ray
      absorptiometry. Ambulatory status was independently associated with changes in
      BMD (p < or = 0.005) 1 year after stroke. The 17 initially wheelchair-bound
      patients had a significant 10% reduction in BMD at the paretic side and 5%
      reduction at the non-paretic side (p < 0.001), while the 23 patients initially
      able to walk had a significant loss (3%) only at the paretic side (p = 0.01). The
      analysis also indicated that the major reduction in BMD took place within the
      first 7 months. Two months after stroke 12 of the wheelchair-bound patients had
      relearned to walk. At the paretic side the 1 year changes in BMD in the patients
      who stayed wheelchair-bound, the patients who re-learned to walk within the first
      2 months and the patients who were able to walk throughout the study were 13%, 8%
      and 3%, respectively, and a statistically significant trend with ambulatory level
      was found (p = 0.007). This study provides clear evidence that lack of mobility
      and weight-bearing early after stroke is an important factor for the greater bone
      loss in the paretic leg, but that relearning to walk within the first 2 months
      after stroke, even with the support of another person, may reduce the bone loss
      after immobilization.

PMID- 10912839
TI  - Bone density in Ehlers-Danlos syndrome.
AB  - Ehlers-Danlos Syndrome (EDS) is the most common inherited disorder of connective
      tissue recognized. The objectives of the present study were to determine bone
      mineral density (BMD) and biochemical markers of bone metabolism in EDS. Twenty
      three subjects with Type III EDS and 23 matched controls underwent BMD
      measurement by dual-Energy X-ray absorptiometry (DXA) of the lumbar spine and
      femoral neck. Health history questionnaires and biochemical markers of bone and
      connective tissue metabolism were also assessed. No significant differences in
      BMD at the lumbar spine or differences in biochemical markers of bone and
      connective tissue metabolism were found between EDS subjects and controls. EDS
      subjects had a significantly decreased BMD at the femoral neck compared with
      controls, but this difference disappeared after adjustment for body height,
      weight and physical activity levels.

PMID- 10912840
TI  - Use of bone densitometry by Ontario family physicians.
AB  - A stratified (urban/rural), computer-generated random sample of 797 Ontario
      members of the College of Family Physicians of Canada received a self
      administered questionnaire by mail. The questionnaire examined current use of
      bone densitometry, focusing on reasons for its use, factors that limit use, and
      features of the report that are helpful to the family physician in subsequent
      patient management. The response rate was 64% (457/711) after excluding 77
      physicians who no longer practice family medicine. Ninety-two percent of the
      physicians used densitometry; of these, 97% ordered the test in the past year.
      Compared with urban physicians, rural physicians were more likely to 'never use
      densitometry' (p=0.04). Rural physicians who reported using densitometry used it
      less frequently (p=0.002), were less likely to have local access (p=0.001), and
      were less confident in its use (p=0.004) than their urban counterparts. Risk
      factors and hormone replacement therapy decision-making were ranked equally as
      the most frequent reasons for ordering the test, followed by follow-up. Few
      physicians identified limits to their use of densitometry. Female physicians used
      densitometry more frequently (p = 0.03) and were more confident in its use (p =
      0.02). Features of the bone density report found to be most helpful were the
      statement of fracture risk, suggestions for further investigation, management and
      follow-up, and percent reduction in bone density compared with age-matched
      controls. The use of bone densitometry by Ontario family physicians is consistent
      with published guidelines. These physicians identified the estimate of fracture
      risk and suggestions for investigation and management as the most helpful
      features of the bone density report. This suggests a role for the incorporation
      of clinical data in bone density reporting.

PMID- 10912841
TI  - Detailed analyses of periarticular osteoporosis in rheumatoid arthritis.
AB  - Periarticular osteopenia is the earliest radiographic sign of rheumatoid
      arthritis (RA). Recent studies using dual-energy X-ray absorptiometry (DXA) have
      indicated that the loss of periarticular BMD can be quantified by whole-hand bone
      mineral density (BMD) measurements. The aim of this study was to analyze
      periarticular BMD in more detail by DXA and quantitative ultrasound (QUS). In a
      cross-sectional study 23 women aged 30-76 years with early RA, mean disease
      duration 26 +/- 19 months, and 18 men aged 42-69 years, mean disease duration 24
      +/- 25 months, were examined. All patients received antirheumatic therapy. The
      reference population consisted of 103 age-matched controls (68 females, 35 males)
      and young healthy controls. BMD measurements were performed using a DXA Expert XL
      densitometer (Lunar). BMD of the whole-hand and two subregions was determined:
      two subchondral regions of interest (S.CH.) were set within the trabecular bone,
      distal to the proximal interphalangeal joints of digits II and III excluding the
      dense subchondral bone of the metacarpophalangeal (MCP) joint and two metacarpal
      regions of interest (MCP) were set including the entire MCP joint of these
      fingers. QUS measurements at the proximal phalanges of digits II-V were performed
      using a DBM Sonic (Igea); amplitude-dependent speed of sound (Ad-SoS) was
      determined. In comparison with whole-hand BMD measurements, bone loss was
      pronounced in patients with a disease duration of 18-72 months at the subchondral
      regions of interest in both genders compared with age-matched controls (women:
      mean BMD loss S.CH. -23%, p<0.001, whole-hand -16%, p<0.001; men: mean BMD loss
      S.CH. -19%, p < 0.05, whole-hand -12%, p<0.05). The bone changes were also shown
      by QUS (women: Ad-SOS values of 1950 +/- 90 m/s in RA vs 2137 +/- 35 m/s in young
      healthy controls (p <0.005); men AD-SOS 1956 +/- 87 m/s in RA vs 2146 +/- 41 m/s
      in young healthy controls (p <0.05)). These results show that BMD and Ad-SOS
      values are significantly lowered in patients with early RA and indicate that
      periarticular osteoporosis in early RA might possibly be better detected using
      detailed hand scan analyses.

PMID- 10912842
TI  - Suitability of the T-score for establishing bone mineral density categories.
AB  - The use of different reference ranges may give rise to different T-score values
      for the same bone mineral density (BMD) value. This study was designed to
      quantify the differences in the classification of a particular population on the
      basis of normal ranges obtained from other reference databases. The T-scores
      obtained in a sample of 148 women by applying the Spanish normal range were
      compared with the normal range obtained in NHANES III for femoral neck.
      Significant differences were found when T-scores were compared, but there were no
      differences in categorizations using the WHO criteria. The application of these
      reference ranges to a female population aged older than 45 years with known BMD
      showed significant differences in classification. In conclusion, the T-score can
      vary according to the normal range used as reference, but it has little influence
      on the categorization of individual patients. However, it may be important when
      applied to a general population.

PMID- 10912843
TI  - Discrimination of proximal hip fracture by quantitative ultrasound measurement at
      the radius.
AB  - Osteoporosis is a disease that culminates in fragility fractures and, therefore,
      imposes major burden on the health economy. In dealing with this worldwide
      condition, it is prudent to use a reliable, inexpensive, portable diagnostic
      means that does not use ionizing radiation and is capable of measuring bone
      properties at several sites. Recently, a quantitative ultrasound device
      (Omnisense) that measures speed of sound (SOS) at multiple skeletal sites was
      introduced. The Omnisense combines the 'axial transmission' mode and the critical
      angle concept. Preliminary reports suggested that of the different skeletal sites
      measured by this device, the distal third of the radius is the preferred
      measurement site for osteoporosis. In this cross-sectional study, SOS was
      determined at the radius using Omnisense in 50 hip-fractured elderly women (group
      F, age 76.1 +/- 6.0 years), 130 elderly controls (group NF, age 71.5 +/- 5.2
      years) and 185 young healthy controls (group YH, age 40.6 +/- 3.0 years). Actual
      SOS was significantly lower in group F compared with group NF (p = 0.0001).
      Whereas SOS T-scores calculated for each woman and stratified into age subgroups
      within each of the study groups indicate decline from -2.22 to -3.56 in group F
      and from -1.56 to -3.17 in group NF, there was an increase from -0.02 to 0.03 in
      group YH. Age- and BMI-adjusted logistic regression for hip fracture
      discrimination indicated an area under the receiver operating characteristic
      curve for hip fracture of 0.79 (95% CI, 0.73-0.86; p = 0.005) and an odds ratio
      of 1.92 (95% CI, 1.22-3.02; p = 0.005). We conclude that SOS measured at the
      radius by Omnisense discriminates subjects with hip fracture. from controls.
      Prospective studies are needed to support the role of Omnisense in assessing the
      risk of hip fracture.

PMID- 10912844
TI  - Long-term persistence of low bone density in orthotopic liver transplantation.
AB  - We determined bone density and metabolism in 46 patients (35 males, 11 females)
      who had undergone liver transplantation 1-48 months previously. Twenty-one
      patients were then followed for the next 24 months. At each visit, blood and
      urine samples for bone and liver metabolism parameters, as well as spinal and
      femoral dual-energy X-ray absorptiometry (DXA) scans, were obtained. Basal spinal
      and femoral density was low (p < 0.001). Patients with pre-transplant cholestatic
      diseases had lower spinal density than all the other subjects (p <0.05) and the
      cumulative methylprednisolone intake was an independent negative predictor of
      total hip density (p < 0.02). At baseline, urinary hydroxyproline and N
      telopeptide were at the upper normal level and decreased only after 24 months of
      follow-up (p < 0.05). During the first year of follow-up, femoral density
      decreased (p < 0.05) and a partial recovery was observed for both spine and femur
      after 24 months. After 12 months, femoral bone density was negatively associated
      with serum cyclosporin A levels (p < 0.005) and cumulative methylprednisolone
      intake (p < 0.05), while the percent decrease in spinal density after the first
      12 months was negatively predicted by mean daily methylprednisolone intake (p <
      0.05). In patients with pre-transplant cholestatic diseases, femoral and spinal
      density increased after the first (p < 0.05) and second year (p < 0.05),
      respectively. In patients with previous post-necrotic cirrhosis, femoral density
      decreased after 12 months (p<0.05) and was still lower than baseline after 24
      months (p < 0.05). However, at the end of the study the cumulative percentage of
      femoral neck osteoporosis was 43%. In conclusion, an elevated prevalence of
      spinal and femoral osteoporosis is present even many years after liver
      transplantation, with immunosuppressive treatment and pre-transplant liver
      disease being the most important pathogenetic factors.

PMID- 10912845
TI  - Does quantitative ultrasound imaging enhance precision and discrimination?
AB  - The aim of this study was to compare quantitative ultrasound (QUS) measurements
      obtained using a new calcaneal QUS imaging device with a conventional non-imaging
      device using fixed transducers. The study group consisted of 340 healthy women
      with no risk factors associated with osteoporosis (176 premenopausal and 164
      postmenopausal) and 83 women with one or more vertebral fractures. All women had
      QUS measurements performed on the Osteometer DTU-one (imaging) and Walker-Sonix
      UBA575+ (non-imaging) devices and bone mineral density (BMD) measurements
      performed at the spine and hip. A subgroup of 81 women had additional dual-energy
      X-ray absorptiometry (DXA) scans at the calcaneus. Short-term standardized
      precision (SP = SD/young adult SD) based on duplicate measurements was
      significantly better on the DTU for broadband ultrasound attenuation (BUA) (SP:
      DTU 0.15 vs UBA 0.21,p = 0.01) and speed of sound (SOS) (SP: DTU 0.14 vs UBA
      0.18, p = 0.01). However, long-term SP of the DTU was comparable to or
      significantly poorer than the SP of the UBA device. The BUA and SOS measurements
      obtained on the DTU and UBA were significantly correlated (r = 0.76 and 0.89 for
      BUA and SOS measurements respectively). The correlations between QUS and BMD
      measurements were all significant, ranging from 0.53 to 0.72. No significant
      improvements in the correlation with axial or peripheral BMD were observed using
      the imaging device. All the QUS measurement parameters showed a significant
      negative relationship between age and years since menopause in the postmenopausal
      group. Annual losses were lower for the DTU for BUA (DTU 0.22 dB/MHz per year vs
      UBA 0.44 dB/MHz per year) but comparable for SOS (DTU 0.29 m/s per-year vs UBA
      0.22 m/s per year). However, when these figures were standardized to take into
      account the clinical range, the annual losses were similar on the DTU and UBA.
      Age-adjusted odds ratios for each SD decline were similar on the DTU for BUA (DTU
      3.2 vs UBA 3.3) and SOS (DTU 3.4 vs UBA 5.1). The corresponding odds ratios for
      BMD at the lumbar spine, femoral neck and total hip were 2.7, 2.9 and 3.3
      respectively. Age-adjusted receiver-operating characteristics analysis yielded
      values for the area under the curve (AUC) ranging from 0.74 to 0.83. The DTU BUA
      AUC of 0.83 was significantly greater than the AUC obtained for UBA BUA and BMD
      measurements at the lumbar spine and femoral neck. Ultrasound imaging at the
      calcaneus was found to improve the standardized precision of BUA and SOS
      measurements in the short term but not in the long term. Neither the correlation
      with BMD nor the discriminatory ability of QUS was improved by utilizing QUS
      images at the calcaneus. The inconsistencies of the imaging system used for this
      study demonstrate that further development is required before it will be possible
      to show improvements in long-term precision.

PMID- 10912847
TI  - Epidemiology of osteoporotic pelvic fractures in elderly people in Finland: sharp
      increase in 1970-1997 and alarming projections for the new millennium.
AB  - The purpose of our epidemiologic study was to determine the current trend in the
      number and incidence of osteoporotic pelvic fractures in Finland, a country with
      a Caucasian population of 5 million. Thus, all Finns 60 years of age or older who
      were admitted to hospitals in 1970-1997 for primary treatment of a first
      osteoporotic pelvic fracture were selected from The National Hospital Discharge
      Register. In each year of the study, the number and the age-specific and age
      adjusted incidences of fractures were expressed as the number of. patients per
      100,000 individuals. The total number of osteoporotic pelvic fractures increased
      considerably in Finland during the study period, from 128 in 1970 to 913 in 1997,
      an average increase of 23% a year. The corresponding fracture incidence (per
      100,000 persons 60 years of age or older) was 20 in 1970 and 92 in 1997. The mean
      age of the patients also increased, from 74 years (1970) to 80 years (1997).
      Despite this, the age-adjusted incidence of osteoporotic pelvic fractures also
      showed a steady increase from 1970 to 1997: in women, from 31 to 103, and in men,
      from 13 to 38 (relative increases were 232% and 192%, respectively). If this
      trend continues, the current number of osteoporotic pelvic fractures in this
      country (about 900 fractures per year) may treble by the year 2030 (about 2,700
      fractures per year). We conclude that the number of osteoporotic pelvic fractures
      in elderly Finns is increasing at a rate that cannot be explained simply by
      demographic changes and therefore effective preventive measures should be
      urgently initiated to control the increasing burden of these age-related
      fractures.

PMID- 10912846
TI  - Short-term increases in bone turnover markers predict parathyroid hormone-induced
      spinal bone mineral density gains in postmenopausal women with glucocorticoid
      induced osteoporosis.
AB  - The purpose of this study was to test the ability of early changes in markers of
      bone turnover to predict subsequent changes in bone mineral density (BMD) induced
      by parathyroid hormone fragment, PTH (1-34), in postmenopausal osteoporotic women
      treated with estrogen and glucocorticoids. Forty-nine postmenopausal women with
      chronic, inflammatory diseases and BMD T-scores < or = -2.5 at the lumbar spine
      or femoral neck who were concurrently treated with estrogen > or = 1 year and
      prednisone 5-20 mg/day for > or = 1 year participated. Subjects were randomized
      to treatment with human PTH (1-34) 400 IU/day or to a control group for 1 year
      and followed for an additional year. Serum and urine were collected at baseline
      and 1, 3, 6, 9, 12, 18 and 24 months for measurement of bone alkaline phosphatase
      (BAP), osteocalcin (OC) and deoxypyridinoline (DPD). We constructed an Uncoupling
      Index (UI) from all three markers (UI = [ZBAP + Zoc]/2 -ZDPD, where the Z-score
      for each marker in each subject was calculated from the mean and standard
      deviation of the study population at baseline). BMD of the lumbar spine and hip
      was measured at baseline and every 6 months thereafter by dual-energy X-ray
      absorptiometry (DXA) and annually by quantitative computed tomography (QCT; spine
      only). BMD of the spine, but not hip (total, femoral neck or trochanter), and
      levels of all three markers increased significantly as a result of PTH treatment
      (p<0.01 compared with controls). The resorption response lagged behind that of
      formation as evidenced by a significant increase (p < 0.05) in the UI for the
      first 9 months of treatment. The UI values and changes from baseline to 1, 3 and
      6 months in BAP, OC and DPD were correlated with the 12- and 24-month changes in
      spine BMD measured both with QCT and with DXA (Spearman's rank coefficients
      <0.76; p<0.05). Most PTH-treated subjects could be identified as biochemical
      responders by least significant change analysis. Following 1 month of therapy,
      BAP and OC identified 65% and 81% as responders, respectively. The responder
      rates were 79%, 79% and 75% for BAP, OC and DPD, respectively by 6 months.
      Responders exhibited a high level of diagnostic accuracy for predicting a gain in
      BMD (areas under the receiver operating characteristic curves exceeding 0.79 for
      QCT and 0.70 for DXA), but not the magnitude of the gain. These data suggest that
      serial bone marker measurements may be useful in identifying skeletal responders
      to an anabolic therapy, such as PTH, in estrogen-replete postmenopausal women
      with glucocorticoid-induced osteoporosis.

PMID- 10912848
TI  - Pregnancy-associated osteoporosis: does the skeleton recover?
AB  - Osteoporosis in pregnancy is a rare clinical problem of unknown cause. If the
      bone loss results from the pregnancy alone it should improve toward normal after
      delivery; in contrast, where bone density was low before pregnancy, due to some
      other secondary cause, significant postpartum improvement might not be expected.
      Thirteen women (age 23-37 years) with pregnancy-associated osteoporosis
      presenting with either pain in the back and vertebral collapse (8 subjects) or
      pain in the hip (5 subjects) had consecutive dual-energy X-ray absorptiometry
      measurements of bone mineral density (BMD) for up to 8 years after an affected
      pregnancy. The BMD results were expressed as a Z-score in relation to an age
      matched mean. The mean initial (0-6 months postpartum) BMD was low in both groups
      and at both sites. In the back pain group the mean spine Z-score (Ll-L4) was 
      3.34 (range -2.25 to -4.66) and mean total hip Z-score was -2.41 (range -1.44 to 
      3.82). In the hip pain group the mean spine Z-score was -2.00 (range -1.48 to 
      2.65) and mean hip Z-score was -2.19 (range -1.12 to -3.26). Subsequent mean hip
      and spine BMD increased significantly toward the lower end of the normal range.
      We conclude that a reversible part of the bone loss is related to the pregnancy
      itself. A low BMD before pregnancy cannot be excluded. Knowledge that the bone
      density increases after an affected pregnancy, combined with the known rarity of
      recurrent symptoms in subsequent pregnancies, is important in prognosis.

PMID- 10912849
TI  - Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a
      prospective study.
AB  - To determine the effect of metabolic control on bone mineral density (BMD) in
      type 1 diabetes mellitus (type 1 DM), we studied BMD (by dual-energy X-ray energy
      absorptiometry) and bone remodeling parameters in 62 patients with type 1 DM both
      before and 7 years after commencement of intensive insulin therapy. Overall
      outcomes after the 7-year treatment included the stabilization of BMD at all
      sites, as well as a significant decrease in tartrate-resistant acid phosphatase
      (TRAP) (4.302 +/- 2.62 vs 2.65 +/- 0.97 IU/I; p=0.0001) and increase in intact
      parathyroid hormone (PTHi) (28.05 +/- 15.7 vs 39.78 +/- 22.41 ng/l; p=0.005).
      Presence of diabetic retinopathy (RTP) versus its absence (non-RTP) was
      associated with lower BMD in femoral neck (FN) (0.831 +/- 0.142 vs 0.756 +/-
      0.153 mg/ cm2; p = 0.03) and Ward's triangle (WT) (0.736 +/- 0.165 vs 0.632 +/-
      0.172 mg/cm2; p=0.03), and with a lower T-score in FN (-0.93 +/- 1.34 vs -1.70 +/
      1.46; p = 0.04) and WT (-0.72 +/- 1.42 vs -1.540 +/- 1.55; p = 0.04) and Z-score
      in FN (-0.591 +/- 1.23 vs -1.132 +/- 1.46; p=0.01). The percentage of patients
      with osteopenia or osteoporosis in the RTP group was significantly higher than in
      the non-RTP group (72% vs 53%, p=0.05; RR= 3.2) and the glycosylated hemoglobin
      (HbA1c) levels of the RTP group were also higher (8.53 +/- 1.6% vs 7.1+/- 1.1%;
      p=0.05). The improvement in metabolic control, increase in body mass index and
      decrease in resorption parameters could contribute to the stabilization of bone
      mass in type I DM but the presence of retinopathy is a critical factor in the
      progression of diabetic osteopenia.

PMID- 10912850
TI  - Deterioration in quality of life following hip fracture: a prospective study.
AB  - To examine longitudinal change in health-related quality of life (HRQoL)
      following hip fracture in elderly subjects, 32 patients with hip fractures and 29
      sex-matched non-fracture control subjects (mean +/- SD age 82 +/- 8 and 86 +/- 6
      years respectively) were enrolled in a prospective, case-control study. Fracture
      subjects completed a generic questionnaire, Short Form 36 (SF-36), and a disease
      targeted measure, the revised Osteoporosis Assessment Questionnaire (OPAQ2), on
      two separate occasions, within 1 week of fracture and 12-15 weeks after fracture.
      Controls completed both questionnaires on two occasions 12 weeks apart. SF-36
      scores were significantly correlated with OPAQ2 in comparable domains of Physical
      Function (r = 0.76), General Health (r = 0.70) and Mental Health/Tension
      (r=0.86). Control subjects had stable scores with the OPAQ2 and SF-36. At 3
      months after fracture there was a significant reduction in HRQoL in the SF-36
      domains Physical Function (-51%), Vitality (-24%) and Social Function (-26%) and
      in the OPAQ2 domains Physical Function (-20%), Social Activity (-49%) and General
      Health (-24%). Hip fracture patients thus had a lower baseline HRQoL and
      experienced a significant deterioration in HRQoL after hip fracture on both the
      SF-36 and OPAQ2. HRQoL should be part of a comprehensive assessment of the costs
      of osteoporosis including fracture-associated morbidity.

PMID- 10912851
TI  - Midline shift after severe head injury: pathophysiologic implications.
AB  - OBJECTIVE: To investigate the mechanism of the adverse effect of midline shift
      after severe traumatic brain injury. METHODS: This study compared averaged
      cerebral metabolic parameters of patients with midline shift > 5 mm (S) on
      initial computerized tomography scan to those of patients with shift < or = 5 mm
      (NS). The effect of an acute subdural hematoma (SDH) was determined by separating
      patients into those with and those without SDH and then re-examining the effect
      of shift in these subgroups. RESULTS: Four hundred fifty-four patients were
      studied. Cerebral metabolic rate of oxygen (CMRO2, in mL/100 g per min) was
      always lower with shift: 1.74 for SDH-S versus 2.21 for SDH-NS (p < 0.001), and
      1.80 for non-SDH-S versus 2.24 for non-SDH-NS (p < 0.001). No other major effects
      of shift were seen in SDH patients. Among non-SDH patients, shift was associated
      with higher intracranial pressure (ICP): 23.1 mm Hg versus 16.3 mm Hg (p <
      0.001). Other differences between shift and nonshift patients in the non-SDH
      group were due at least in part to interventions to treat the elevated ICP.
      CONCLUSION: Midline shift after severe traumatic brain injury is associated with
      reduced CMRo2, regardless of whether or not SDH is present. The deleterious
      effects of subdural blood may be related more to the mass effect of large SDHs
      than to the biochemical abnormalities caused by small amounts of blood in the
      subdural space.

PMID- 10912852
TI  - Sepsis after severe injury interrupts caspase-dependent processing of interleukin
      18.
AB  - BACKGROUND: Cysteine proteases (caspases) participate in the activation process
      of interleukin-18 (IL-18), a key cytokine for septic organ failure. This study
      evaluates the influence of caspase blockade on secretion of IL-18 into whole
      blood in patients with multiple injuries and in patients with severe sepsis.
      METHODS: Heparinized blood was collected from patients with multiple injuries,
      from septic patients, as well as from healthy humans. Whole blood was stimulated
      for 24 hours with lipopolysaccharide (LPS) or Staphylococcus aureus in the
      presence or absence of the caspase inhibitors Z-VAD and Z-DEVD. IL-18 was
      measured by enzyme-linked immunosorbent assay. RESULTS: S. aureus Cowan strain
      differentially increased the release of IL-18 in the three study populations,
      whereas LPS was ineffective. Z-VAD and to a lesser degree Z-DEVD decreased (p <
      0.05) S. aureus Cowan strain I-induced secretion of IL-18 into whole blood from
      control subjects and trauma patients. Caspase inhibitors did not influence
      release of IL-18 into whole blood from septic patients. CONCLUSION: Secretion of
      IL-18 into whole blood from healthy humans and trauma patients can be effectively
      controlled through blockade of caspase activity. In contrast, during sepsis,
      alternative mechanisms may regulate secretion of IL-18.

PMID- 10912853
TI  - Predictors of outcome in trauma during pregnancy: identification of patients who
      can be monitored for less than 6 hours.
AB  - BACKGROUND: The first objective of this study was to identify risk factors in
      pregnant patients suffering blunt trauma predictive for uterine contractions,
      preterm labor, or fetal loss. The second objective was to identify patients who
      can safely undergo fetal monitoring for 6 hours or less after blunt trauma by
      selecting out those patients demonstrating the identified risk factors. METHODS:
      A retrospective chart review was performed from January 1, 1990, through December
      31, 1998. Charts were reviewed for numerous possible risk factors for adverse
      outcomes. Statistical analysis was performed by using logistic regression.
      RESULTS: A total of 271 pregnant patients admitted after blunt trauma were
      identified. Risk factors significantly predictive of fetal death included
      ejections, motorcycle and pedestrian collisions, maternal death, maternal
      tachycardia, abnormal fetal heart rate, lack of restraints, and Injury Severity
      Score > 9. Risk factors significantly predictive of contractions or preterm labor
      included gestational age >35 weeks, assaults, and pedestrian collisions.
      CONCLUSION: Pregnant patients who present after blunt trauma with any of the
      identified risk factors for contractions, preterm labor, or fetal loss should be
      monitored for at least 24 hours. Patients without these risk factors can safely
      be monitored for 6 hours after trauma before discharge.

PMID- 10912854
TI  - Maintaining survivors' values of left ventricular power output during shock
      resuscitation: a prospective pilot study.
AB  - OBJECTIVE: Maintaining left ventricular power output (LVP) > 320 mm Hg x L/min/m2
      during resuscitation has been retrospectively associated with faster resolution
      of acidosis and survival after posttraumatic shock. The purpose of this
      prospective study was to evaluate the effects of maintaining LVP above this
      threshold during resuscitation on base deficit clearance, organ failure, and
      survival. METHODS: This was a study of a consecutive series of critically injured
      patients (PWR) monitored with a pulmonary artery catheter during initial
      resuscitation. LVP, calculated as cardiac index-(mean arterial pressure-central
      venous pressure), was maintained >320 mm Hg x L/min/m2 via a predefined protocol
      by using ventricular pressure-volume diagrams. Outcome was assessed by base
      deficit clearance (<6 mEq/L) in <24 hours, lowest base deficit in the first 24
      hours after admission (24-hr base deficit), organ dysfunctions/patient, and
      survival. Results were compared with 39 control patients (OXY) with identical
      enrollment criteria from a previous prospective study who were resuscitated based
      on oxygen transport criteria. RESULTS: Twenty patients were studied over a 6
      month period. Mean LVP during resuscitation in the PWR group was 360 +/- 100 mm
      Hg x L/min/m2. Admission base deficit was similar between the two groups (PWR 11
      +/- 4.2 vs. OXY 11 +/- 5.8 mEq/L;p = 0.66). More PWR patients cleared base
      deficit in < 24 hours than OXY patients (16 of 20 vs. 17 of 39, p = 0.009,
      Fisher's exact test), and the PWR patients had a significantly lower 24-hr base
      deficit (3.9 +/- 3.7 vs. 7.1 +/- 4.6 mEq/L, p = 0.01). Organ dysfunction rate was
      lower in the PWR group (2.1 +/- 1.5 vs. 3.2 +/- 1.4 organ dysfunctions/patient, p
      = 0.007). Survival in the PWR group was 15 of 20, versus 21 of 39 in the OXY
      group (p = 0.10). CONCLUSION: Prospectively maintaining LVP above 320 mm Hg x
      L/min/m2 during resuscitation is an achievable goal. It is associated with
      improved base deficit clearance and a lower rate of organ dysfunction after
      resuscitation from traumatic shock.

PMID- 10912855
TI  - Alterations in glucose-6-phosphatase gene expression in sepsis.
AB  - BACKGROUND: The influence of sepsis on the expression and activity of hepatic
      glucose-6-phosphatase (Glu-6-Pase) was examined during the early hyperglycemic
      phase and the later hypoglycemic phase. METHODS: Sepsis was induced in
      anesthetized, fasted rats by cecal ligation and puncture, and liver samples were
      taken at 0, 0.5, 1, 1.5, and 20 hours after cecal ligation and puncture. RESULTS:
      The mRNA abundance of hepatic Glu-6-Pase increased fourfold at 0.5 hours over
      healthy control values, two-fold after 1 hour, and returned to normal after 1.5
      hours. This finding was followed by a corresponding increase in Glu-6-Pase
      activity and was coincident with increased plasma glucose levels and decreased
      liver glucose-6-phosphate (Glu-6-P) at 0.5 and 1 hours. Plasma insulin and
      glucagon levels remained unchanged during this period, whereas corticosterone
      levels increased 2.5-fold over control values. At 20 hours cecal ligation and
      puncture, plasma glucose levels returned to normal, coincident with a 90%
      reduction in Glu-6-Pase mRNA abundance. Glu-6-Pase activity and Glu-6-P
      concentration returned to normal levels, while insulin, glucagon, and
      corticosterone levels increased significantly, i.e., 40-fold, 6.5-fold, and 6
      fold, respectively. CONCLUSION: The initial rise and subsequent decline in blood
      glucose correlate very well with a corticosterone-dependent induction of hepatic
      Glu-6-Pase, mRNA, and protein, followed by an insulin-dependent suppression of
      its expression.

PMID- 10912856
TI  - Use of an unmanned police car to reduce traffic speed.
AB  - OBJECTIVE: Motor vehicle collisions are the most common mechanism of traumatic
      death. Speeding is often implicated as a causal factor in motor vehicle crashes.
      One potential intervention, to prevent speeding, is the placement of a roadside
      unmanned police car. This study sought to answer the following questions: is
      speeding reduced by this intervention, does this intervention lose effectiveness
      over time, and when the car is removed, do motorists resume speeding? METHODS: A
      radarless speed detector was placed on a roadway that had a history of speed
      related collisions. Baseline speeds were recorded for 12 days. Thereafter, an
      unmanned police cruiser was parked near the road, and speeds were recorded for 10
      days. The police car was removed, and data collection continued 1 more week. The
      difference between the proportion of motorists exceeding 45-mph in the baseline
      period and the decoy intervention period was tested by using a chi2 test.
      RESULTS: During the baseline surveillance, 72.0% of vehicles (186,578 of 259,074
      motorists) had speeds greater than 45 mph. After placement of the unmanned police
      car, 41.0% of motorists (92,272 of 225,026 motorists) exceeded 45 mph (p <
      .0001). Over the 10-day study period, when the decoy police car was in place, the
      percentage of motorists exceeding 45 mph gradually increased from 27.2% to 47.4%.
      Upon removal of the police car, speeding returned approximately to baseline, with
      67.5% of motorists (120,640 of 178,752 motorists) exceeding 45-mph. CONCLUSION:
      Parking an unmanned police car beside a road was associated with a large
      reduction in speeding over a 10-day period. Removal of the unmanned police car
      resulted in a return to preintervention speeding.

PMID- 10912858
TI  - Nonoperative management of hepatic, splenic, and renal injuries in adults with
      multiple injuries.
AB  - BACKGROUND: Nonoperative management (NOM) of abdominal solid organ (ASO; liver,
      spleen, kidney) injuries from blunt trauma in adults has gained acceptance, but
      multisystem trauma remains a relative contraindication to NOM. METHODS: We
      reviewed the charts of 126 adult patients who underwent NOM of an ASO injury for
      success of NOM, transfusions, and complications. Patients were divided into two
      groups: group I had isolated ASO injuries (n = 48); group II had an ASO injury
      and at least one additional injury with an Abbreviated Injury Score > or = 2 (n =
      78). RESULTS: NOM was successful 89.6% of group I and 93.6% of group II patients
      (p = 0.55). Group II had higher Injury Severity Scores (20.7 +/- 9.8 vs. 8.3 +/-
      4.9 p < 0.05) and transfusion requirements (30.8% vs. 14.6%,p < 0.05) than group
      I. Complication rates were not different (group I, 20.8% vs. 26.9% group II, p =
      0.58). CONCLUSION: NOM of ASO injuries may attempted in adult patients with
      multiple injuries without increased morbidity.

PMID- 10912857
TI  - Lactated ringer's solution and hetastarch but not plasma resuscitation after rat
      hemorrhagic shock is associated with immediate lung apoptosis by the up
      regulation of the Bax protein.
AB  - BACKGROUND: We previously demonstrated that the type of resuscitation fluid used
      in hemorrhagic shock affects apoptosis. Unlike crystalloid, whole blood seems to
      attenuate programmed cell death. The purpose of this study was to determine
      whether the acellular components of whole blood (plasma, albumin) attenuated
      apoptosis and to determine whether this process involved the Bax protein pathway.
      METHODS: Rats were hemorrhaged 27.5 mL/kg, kept in hypovolemic shock for 75
      minutes, then resuscitated over 1 hour (n = 44). Control animals underwent
      anesthesia only (sham, n = 7). Treatment animals were bled then randomly assigned
      to the following resuscitation groups: no resuscitation (n = 6), whole blood (n =
      6), plasma (n = 6), 5% human albumin (n = 6), 6% hetastarch (n = 7), and lactated
      Ringer's solution (LR, n = 6). Hetastarch was used to control for any colloid
      effect. LR was used as positive control. Immediately after resuscitation, the
      lung was collected and evaluated for apoptosis by using two methods. TUNEL stain
      was used to determine general DNA damage, and Bax protein was used to
      specifically determine intrinsic pathway involvement. RESULTS: LR and hetastarch
      treatment resulted in significantly increased apoptosis in the lung as determined
      by both TUNEL and Bax expression (p < 0.05). Plasma infusion resulted in
      significantly less apoptosis than LR and hetastarch resuscitation. Multiple cell
      types (epithelium, endothelium, smooth muscle, monocytes) underwent apoptosis in
      the lung as demonstrated by the TUNEL stain, whereas Bax expression was limited
      to cells residing in the perivascular and peribronchial spaces. CONCLUSION:
      Apoptosis after volume resuscitation of hemorrhagic shock can be affected by the
      type of resuscitation fluid used. Manufactured fluids such as lactated Ringer's
      solution and 6% hetastarch resuscitation resulted in the highest degree of lung
      apoptosis. The plasma component of whole blood resulted in the least apoptosis.
      The process of apoptosis after hemorrhagic shock resuscitation involves the Bax
      protein.

PMID- 10912859
TI  - Effect of trauma system maturation on mortality rates in patients with blunt
      injuries in the Finger Lakes Region of New York State.
AB  - BACKGROUND: New York State instituted a statewide trauma system beginning in
      1990. By 1993, that system included uniform emergency medical system triage
      guidelines, designated trauma centers, transfer agreements between trauma centers
      and noncenters, and a trauma registry containing data on seriously injured
      patients in each region and the state as a whole. We reviewed the first 4 years
      of registry data for the Finger Lakes Region to determine what effects the
      institution of a trauma system has had on the outcome of trauma care in this
      region. DESIGN: Retrospective review of a regional trauma database. METHODS: All
      qualifying injured patients in the region were entered into the registry
      beginning in 1993. Data from 1993 through 1996 for patients with blunt injuries
      were analyzed by both Trauma and Injury Severity Score (TRISS) methodology and
      logistic regression analysis. For comparison, two time periods were defined: 1993
      1994 and 1995-1996. Outcomes for the two time periods were stratified by Revised
      Trauma Score and the presence or absence of head and/or cervical spine injury,
      and then compared by hospital type (regional trauma center, area trauma center,
      and noncenters). RESULTS: In the later time period, there was a statistically
      significant decrease in the region-wide mortality rate. This was associated with
      a marked improvement in performance of the noncenters and with an increase in the
      proportion of patients who received definitive care at a trauma center.
      CONCLUSIONS: Improved outcomes for patients with blunt trauma can occur early in
      the implementation of a trauma system. This improvement may be attributable in
      part to changes in field triage and early transport to trauma centers.

PMID- 10912860
TI  - Mortality after successful transcatheter arterial embolization in patients with
      unstable pelvic fractures: rate of blood transfusion as a predictive factor.
AB  - BACKGROUND: To determine the factors predictive of mortality in patients with
      unstable pelvic fractures after successful transcatheter arterial embolization.
      METHODS: A retrospective study of pelvic fractures between May of 1995 and April
      of 1998 was performed. Of 507 patients, 17 who were unstable underwent
      embolization. The success rate of embolization and the mortality rate after
      successful embolization were reviewed. Predictive factors (contrast medium
      extravasation, initial blood pressure, Injury Severity Score, timing of external
      fixation, time to angiography, volume of blood transfusion, rate of blood
      transfusion) of the final outcome were statistically analyzed. RESULTS:
      Embolization was 100% effective in stopping pelvic hemorrhage. The mortality of
      patients treated successfully with embolization was 17.6%. Among the predictive
      factors analyzed, only the rate of blood transfusion before embolization, 11.3 +/
      11.0 units/h (death) versus 3.2 +/- 1.9 units/h (survival) showed statistical
      significance with an odds ratio of 1.62 (95% confidence interval, 1.07-2.46).
      CONCLUSION: The success rate of embolization was 100% in stopping arterial
      hemorrhage of unstable pelvic fractures. The survival rate after successful
      embolization was 82.4%. Patients who had rapid blood transfusion before
      embolization had a poor final outcome. The risk of dying increased by 62% for
      every 1 unit/h increase of transfusion rate.

PMID- 10912861
TI  - Evaluation of unstable cervical spine injury: a 6-year experience.
AB  - BACKGROUND: The diagnosis of the unstable cervical spine, and its subsequent
      management can be difficult and a missed cervical spine injury can obviously have
      devastating consequences. METHODS: This study describes a 6-year experience with
      these injuries and presents an algorithm for their evaluation. The case records
      of 100 consecutive patients who underwent an operative procedure for an unstable
      cervical spine injury were reviewed. RESULTS: The population and injury
      characteristics were similar to that of previous studies. The process of
      evaluation of the spine was robust but failed to identify two unstable
      ligamentous injuries not detected on initial radiologic examination. Ten patients
      whose injuries were missed at other hospitals were identified by using this
      system. CONCLUSION: A systematic, well-structured approach to the potentially
      injured cervical spine allows safe and effective diagnosis and management of
      these patients. Failure to adhere to basic principles will result in missed
      unstable cervical spine injuries.

PMID- 10912862
TI  - Treatment of humeral shaft fractures by closed fixation using multiple
      intramedullary Kirschner wires.
AB  - BACKGROUND: The purpose of this study is to present the results of closed
      fixation of humeral shaft fractures with multiple intramedullary Kirschner wires.
      METHODS: Twenty-nine humeral shaft fractures in patients 14 to 60 years old were
      treated by closed fixation with multiple intramedullary Kirschner wires. Each
      patient was placed supine on the table and was administered general anesthesia.
      The fractured arm was held vertically up by a transolecranon traction, while the
      C-arm was kept parallel to the ground and opposite to the affected arm. A
      cortical window was created approximately 1.5 cm proximal to the olecranon fossa,
      after splitting the triceps. Under fluoroscopic control, multiple Kirschner wires
      were introduced retrograde therein, into the medullary cavity, to reach the
      humeral head. The wire tips were kept splayed to stabilize the fracture.
      Postoperatively, the limb was supported by an arm sling. RESULTS: Twenty-five
      fractures (86.4%) healed with excellent clinical and functional results, in an
      average of 11 weeks. Union was delayed in two patients, and one fracture had a
      nonunion after repeated trauma. Movements at the shoulder and the elbow were
      excellent to good in 27 patients (93%), whereas 2 patients (6.8%) had significant
      limitation of extension at the elbow. CONCLUSION: This technique has been found
      simple and effective in providing a stable fixation of transverse and short
      oblique fractures of the humeral diaphysis. Further study is required to evaluate
      this procedure in more extensive fracture patterns, as well as to compare the
      results with other methods of internal fixation.

PMID- 10912863
TI  - Neutrophil elastase may play a key role in developing symptomatic disseminated
      intravascular coagulation and multiple organ failure in patients with head
      injury.
AB  - OBJECTIVE: To study the mechanism associated with the development of symptomatic
      disseminated intravascular coagulation (DIC) after head injury. METHODS: Plasma
      parameters were analyzed in patients with symptomatic (group A, n = 10) and
      asymptomatic DIC (group B, n = 15) induced by head injury, and in patients in
      whom DIC was caused by sepsis (group C, n = 10). RESULTS: Levels of fibrinogen,
      alpha2PI-plasmin complex and platelets in group A (58.1 mg/dL, 22.4 microg/mL,
      16.0 x 10(4)/ mm3) and group B (98.3, 22.1, 16.6 x 10(4)) were comparable, but
      differed significantly from those in group C (297.4, 2.4, 6.3 x 10(4)).
      Significant differences were observed between groups A and B in both neutrophil
      elastase (1,528 vs. 293 microg/ml) and D-dimer (42.1 vs. 17.6 microg/mL).
      CONCLUSION: Neutrophil elastase may be implicated in the development of
      symptomatic DIC after head injury, whose characteristics include "enhanced
      fibrinolysis with minimal platelet loss."

PMID- 10912864
TI  - Multiple selectin blockade with a small molecule inhibitor downregulates liver
      chemokine expression and neutrophil infiltration after hemorrhagic shock.
AB  - BACKGROUND: The purpose of this study was to investigate the regulatory effect of
      a small molecule selectin inhibitor in the liver by examining the functional,
      structural, and survival response of animals subjected to hemorrhagic shock and
      to determine the liver infiltration of neutrophils and the regulation of
      chemokine expression. Selectins play an important role in the development of the
      lesions associated with ischemia/reperfusion and hemorrhagic shock. Blocking
      individually the selectin family of adhesion molecules with monoclonal antibodies
      has resulted in better organ function and survival. To our knowledge, there are
      no studies demonstrating the beneficial effect of multiple selectin blockade with
      a small molecule inhibitor under conditions of hemorrhagic shock. METHODS: Forty
      eight Sprague-Dawley rats were subjected to hemorrhagic shock. Three groups of
      animals were included (n = 16/group), i.e., the sham, control, and treated
      groups, which received a small molecule selectin inhibitor (TBC-1269) at 25 mg/kg
      body weight after the bleeding began. The following parameters were evaluated:
      fluid requirements during resuscitation, liver injury tests (aspartate
      aminotransferase, alanine aminotransferase), liver histology and myeloperoxidase,
      and macrophage inflammatory protein-2 mRNA and cytokine-induced neutrophil
      chemoattractant mRNA in liver tissue, and animal survival at 3 days. Statistical
      analysis included Student's t test and analysis of variance when indicated.
      RESULTS: Significant improvement in liver function and histology was noted in the
      treated group. Survival was also improved, although it is not known whether liver
      failure was the most proximate cause of lethality. Infiltration of neutrophils,
      measured by tissue myeloperoxidase, was significantly decreased in livers of
      treated animals. No significant changes were noted in fluid requirements. The
      small molecule selectin inhibitor group showed a down-regulating effect on liver
      macrophage inflammatory protein-2 and cytokine-induced neutrophil chemoattractant
      mRNA expression associated with less accumulation of neutrophils in the liver.
      CONCLUSION: This study supports the role that selectins play in the pathogenesis
      of hemorrhagic shock. The mechanism of protection seen after multiple selectin
      blockade (TBC-1269) centered, in part, around the infiltration of liver
      neutrophils, probably dependent on the induction of macrophage inflammatory
      protein-2 and cytokine-induced neutrophil chemoattractant mRNA expression in
      liver tissue.

PMID- 10912865
TI  - Hepatic blood flow and oxygen consumption after burn and sepsis.
AB  - BACKGROUND: Alteration in the hepatic circulation after burn and in sepsis seems
      to be an essential component in the development of multiple organ failure.
      METHODS: Female pigs (n = 12, 20-25 kg) were instrumented 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 six of them received 40% total body surface area third-degree
      burn. A total of 100 microg/kg Escherichia coli LPS was intravenously
      administered at 18 hours after burn. All animals were studied for 42 hours.
      RESULTS: Thermal injury resulted in a 48% decrease in hepatic arterial blood flow
      despite maintenance of normal cardiac output, resulting in a fall in hepatic
      oxygen delivery rate. Portal venous blood flow showed a 32% increase at 4 hours
      after burn. Post-LPS portal blood flow was significantly reduced for a period of
      8 hours (51% of baseline (bl), p < 0.05 analysis of variance [ANOVA]). The
      hepatic arterial blood supply was also significantly reduced (12-67% of bl, p <
      0.05 ANOVA) during the first 4 hours after LPS, indicating loss of the hepatic
      arterial response. The following 12 hours, a hepatic reperfusion phase was
      observed with an elevation of the hepatic arterial blood flow to 152% of bl (p <
      0.05 ANOVA). Postburn endotoxemia resulted in a significant decrease of hepatic
      oxygen delivery (88%) and hepatic oxygen consumption (79%). Although the burn
      injury did not affect the portal venous pressure, postburn endotoxemia caused a
      significant portal hypertension during a period of 8 hours (225% of bl, p < 0.05
      ANOVA). CONCLUSION: Postburn sepsis amplifies the selective vasconstrictive
      impact of thermal injury on hepatic arterial blood flow, yielding a pronounced
      ischemia/ reperfusion injury, associated with a critical reduction of hepatic
      oxygen delivery and consumption. A postburn septic challenge induces portal
      hypertension, which may account for previously documented gut barrier
      dysfunction.

PMID- 10912866
TI  - Dietary olive oil enhances murine lymphocyte calcium uptake.
AB  - BACKGROUND: Dietary lipids enhance immune function and improve outcome from
      injury or infection in animal models. We tested the hypothesis that amount, type,
      or both, of dietary lipid increases intracellular calcium concentration, a
      surrogate for lymphocyte activation. METHODS: Mice were fed 2 weeks on
      semipurified diets with 5% (by weight [w/w]), 10% (w/w), or 20% (w/w) dietary fat
      consisting of coconut, olive, safflower, or linseed oil. Changes in intracellular
      calcium concentration after mitogen stimulation of splenic lymphocytes was
      estimated by using flow cytometry. RESULTS: Olive oil diets increase
      intracellular calcium concentration after concanavalin A, lipopolysaccharide, and
      CD3 stimulation. On the other hand, linseed oil (which is high in omega-3 fatty
      acids, which have been shown in other studies to enhance immune function)
      depresses intracellular calcium levels. The amount of dietary fat had no effect
      on intracellular calcium. CONCLUSION: Olive oil merits further study in the
      application of nutritional pharmacology to immunomodulation of the critically
      injured, because it may enhance lymphocyte function.

PMID- 10912867
TI  - Accelerated healing with a mesh autograft/allodermal composite skin graft treated
      with silver nylon dressings with and without direct current in rats.
AB  - PURPOSE: Evaluation of the healing and persistence of a meshed composite skin
      graft applied without immunosuppression. METHODS: The contraction of wounds
      grafted with 9:1 split-thickness autograft/1.5:1 allodermal mesh composite skin
      grafts (auto/allo MCSGs) was investigated. No immunosuppressive agent was
      applied. Male ACI rats and female Lewis rats reciprocally served as allodermis
      graft donors and recipients. Autograft/dermal autograft and allograft/dermal
      allograft MCSGs were the controls. RESULTS: AT 3 months after grafting, when
      epithelized auto/allo MCSG wounds were measured by computerized morphometric
      analysis, the silver nylon (SN) dressing group displayed less contraction than
      the Vaseline (petroleum jelly) dressing group (p < 0.003), and direct current
      treatment (SNDC) was more effective than SN (p < 0.005). The histologic
      structures of the hair follicles appear to confine the rejection process to the
      allogeneic follicles of the graft. The focal nature of the rejection process and
      the relatively low antigenicity of the dermal matrix allowed the survival of the
      allodermis layer. Although direct current significantly enhanced MCSG healing, SN
      and SNDC were not the immunosuppressive agents that were confirmed. CONCLUSION:
      This type of MCSG can heal without immunosuppressive treatment.

PMID- 10912868
TI  - Half-life of blood carboxyhemoglobin after short-term and long-term exposure to
      carbon monoxide.
AB  - BACKGROUND: In models of smoke inhalation injury and carbon monoxide poisoning
      blood carboxy-hemoglobin (COHb) levels decrease faster than predicted by the
      generally recognized half-life of COHb. We studied the effects of duration of
      exposure to carbon monoxide (CO) on the subsequent CO elimination. METHODS: Each
      of four sheep were insufflated with CO gas mixtures either for a few minutes
      (short-term exposure) or for several hours (long-term exposure), then ventilated
      with air for 3 hours. Serial COHb concentrations were analyzed by using a two
      compartment, single central outlet mathematical model. RESULTS: Short-term
      exposures exhibited biphasic decreases of COHb concentration compatible with a
      two-compartment model; an initial rapid decrease (half-life 5.7 +/- 1.4 minutes)
      was followed by a slower phase (103 +/- 20.5 minutes). Long-term exposures
      exhibited almost monophasic decreases, which were nevertheless compatible with
      the model (half-life, 21.5 +/- 2.1 and 118 +/- 11.2 minutes). CONCLUSION: This
      study demonstrated different patterns of CO elimination curve, which suggests
      distribution of CO to two compartments having different rates of equilibration.

PMID- 10912869
TI  - Prevention of venous thromboembolism after injury: an evidence-based report--part
      I: analysis of risk factors and evaluation of the role of vena caval filters.
AB  - BACKGROUND: Trauma surgeons use a variety of methods to prevent venous
      thromboembolism (VT). The rationale for their use frequently is based on
      conclusions from research on nontrauma populations. Existing recommendations are
      based on expert opinion and consensus statements rather than systematic analysis
      of the existing literature and synthesis of available data. The objective is to
      produce an evidence-based report on the methods of prevention of VT after injury.
      METHODS: A panel of 17 national authorities from the academic, private, and
      managed care sectors helped design and review the project. We searched three
      electronic databases (MEDLINE, EM-BASE, and Cochrane Controlled Trial Register)
      to identify articles relevant to four key questions: methods of prophylaxis,
      methods of screening, risk factors for VT, and the role of vena caval filters.
      The initial 4,093 titles yielded 73 articles for meta-analysis. A random-effects
      model was used for all pooled results. Study quality was evaluated by previously
      published quality scores. In this article (part I), we report on the question
      ranked by the experts as the most important, i.e., Which is the best method to
      prevent VT?, and also on the incidence of deep venous thrombosis and pulmonary
      embolism in trauma patients. RESULTS: The incidence of deep venous thrombosis and
      pulmonary embolism reported in different studies varies widely. The pooled rates
      are 11.8% for deep venous thrombosis and 1.5% for pulmonary embolism. Only a few
      randomized controlled trials have evaluated the methods of VT prophylaxis among
      trauma patients, and combining their data is difficult because of different
      designs and preventive methods used. The quality of most studies is low. Meta
      analysis shows no evidence that low-dose heparin, mechanical prophylaxis, or low
      molecular-weight heparin are more effective than no prophylaxis or each other.
      However, the 95% confidence intervals of many of the comparisons are wide;
      therefore, a clinically important difference may exist. CONCLUSION: The trauma
      literature on VT prophylaxis provides inconsistent data. There is no evidence
      that any existing method of VT prophylaxis is clearly superior to the other
      methods or even to no prophylaxis. Our results cast serious doubt on the existing
      policies on VT prophylaxis, and we call for a large, high-quality, multicenter
      trial that can provide definitive answers.

PMID- 10912870
TI  - Prevention of venous thromboembolism after injury: an evidence-based report--part
      II: analysis of risk factors and evaluation of the role of vena caval filters.
AB  - OBJECTIVE: In part II, we describe the results of the literature search and data
      analysis concerning risk factors for venous thromboembolism and the role of vena
      caval filters (VCF) in preventing pulmonary embolism. METHODS: The methodology
      used in part I was used in part II. RESULTS: Spinal fractures and spinal-cord
      injuries increase the risk for development of deep venous thrombosis (DVT) by
      twofold and threefold, respectively. Patients with DVT were an average of 9 years
      older than patients without DVT. No specific age cut-off point for increased risk
      could be established because data could not be combined across studies. Patients
      with prophylactically inserted VCF had a lower incidence of pulmonary embolism
      (0.2%) compared with concurrently managed patients without VCF (1.5%) or
      historical controls without VCF (5.8%). These results are reported on
      uncontrolled studies with observational design. CONCLUSION: Spinal injuries,
      spinal cord injuries, and age are risk factors for development of DVT.
      Prophylactic placement of VCF in selected trauma patients may decrease the
      incidence of pulmonary embolism. Future research with well-designed studies is
      required to provide definitive answers.

PMID- 10912871
TI  - Whole blood transfusion for exsanguinating coagulopathy in a US field surgical
      hospital in postwar Kosovo.
AB  - An urgent blood drive in which active duty military field surgical hospital
      personnel volunteered to donate whole blood was conducted, and administration of
      warm, whole blood prevented the exsanguination of a normothermic coagulopathic
      patient who had received a massive transfusion. In austere care settings in which
      full blood banking capability may not be available, physicians should consider
      that exsanguinating hemorrhage can potentially be controlled surgically, but
      nonsurgical bleeding requires specific replacement therapy, and whole blood may
      be the best selection for repleting deficiencies of components that are otherwise
      unavailable.

PMID- 10912872
TI  - Gunshot wound to a duplicate ureter: successful treatment with
      ureteroureterostomy.

PMID- 10912873
TI  - Transperitoneal screw fixation of the sacroiliac joint.

PMID- 10912874
TI  - Diaphragmatic rupture presenting 50 years after the traumatic event.

PMID- 10912875
TI  - Delayed development of obstructive jaundice and pancreatitis resulting from
      traumatic intramural hematoma of the duodenum: report of a case requiring
      deferred laparotomy.

PMID- 10912876
TI  - Small bowel necrosis associated with early postoperative jejunal tube feeding in
      a trauma patient.
AB  - Several investigators have reported the association of small bowel ischemia and
      necrosis with needle catheter jejunostomy. We report a case of small bowel
      necrosis with continuous jejunal tube feeding and review the pathogenesis
      implicated in feeding-induced bowel necrosis.

PMID- 10912877
TI  - Splitting of the tentorium leaves by orbital injury.

PMID- 10912878
TI  - Priming of neutrophil [Ca2+]1 signaling and oxidative burst by human fracture
      fluids.

PMID- 10912879
TI  - Effectiveness of state trauma systems in reducing injury-related mortality.

PMID- 10912880
TI  - Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal
      muscle.
AB  - PURPOSE: To examine the effects of prolonged systemic administration of
      diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective
      indices of exercise-induced muscle damage in humans. METHODS: Fifty-four
      volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized
      double-blind, placebo-controlled trial. To achieve steady-state tissue levels,
      either placebo or diclofenac was orally administered two times a day for 27
      consecutive days. A strenuous 20-min stepping exercise program, about which the
      subjects were unfamiliar, was conducted on day 15. Creatine kinase (CK)
      activities were measured immediately before the exercise session and on days 16,
      18, and 27. Vastus lateralis muscle samples were obtained immediately before
      exercise and on day 27 for subsequent histological characterization of muscle
      inflammation. RESULTS: The preexercise muscle samples revealed no difference in
      muscle damage between the two groups. However, the postexercise muscle samples
      showed that the diclofenac-treated group demonstrated less muscle tissue damage
      than placebo-treated subjects (P = 0.002). The administration of diclofenac also
      resulted in a significant lowering of post-/pre-exercise CK ratios on days 18 (P
      = 0.03) and 27 (P = 0.02) compared with the placebo group, an indirect finding
      that supports the possibility of diclofenac reducing exercise-induced muscle
      damage. CONCLUSION: These findings demonstrate preadministration of diclofenac
      (in accordance with tissue half-life pharmacokinetics) significantly reduces
      quantitative indices of exercise-induced skeletal muscle damage in human muscle.

PMID- 10912881
TI  - Left ventricular contractility and function at peak aerobic and anaerobic
      exercises.
AB  - PURPOSE: The present study compared and evaluated left ventricular function and
      contractility at peak incremental aerobic type exercise and all-out explosive
      anaerobic effort in young healthy trained subjects. METHODS: Twenty-two young
      healthy trained subjects (19 +/- 1 yr) were studied by two-dimensional direct M
      mode echocardiography at peak aerobic and at peak all-out anaerobic exercises,
      performed on cycle ergometer. RESULTS: All subjects completed the study without
      any electrocardiographic abnormalities. Significant (P < 0.05) differences
      between the aerobic and the anaerobic efforts were noted for peak cardiac output
      (24 +/- 2.0 and 15.0 +/- 1.1 L x min (-1), respectively), left ventricular
      pressure-volume ratio (5.8 +/- 0.6 and 4.7 +/- 0.5 respectively), end systolic
      volume (33 +/- 4 and 42 +/- 5 mL, respectively), ejection fraction (79 +/- 7 and
      66 +/- 5%, respectively), and total peripheral resistance (TPR) (367 +/- 90 and
      704 +/- 90 dynes x s(-1) x cm(- 5), respectively). CONCLUSIONS: These data
      suggest that left ventricular at peak all out anaerobic effort differed markedly
      from those observed at peak aerobic exercise. These differences are presumably
      due to the different after-load responses between the two exercise modes.
      Therefore, it is suggested that anaerobic-type effort should be performed with
      great caution in normal young healthy subjects.

PMID- 10912882
TI  - Muscle damage and resting metabolic rate after acute resistance exercise with an
      eccentric overload.
AB  - PURPOSE: The purpose of this investigation was to determine whether muscle damage
      caused from acute resistance exercise with an eccentric overload would influence
      resting metabolic rate (RMR) up to 72 h postexercise in resistance-trained (RT)
      and untrained (UT) subjects. METHODS: Nine RT and 9 UT male subjects (mean +/-
      SD; age = 20.7 +/- 2.1 yr; body mass = 79.0 +/- 1.4 kg; height = 178.4 +/- 3.1
      cm; and body fat = 10.2 +/- 1.6%) were measured for RMR, creatine kinase
      concentration ([CK]), and rating of perceived muscle soreness (RPMS) on five
      consecutive mornings. To induce muscle damage, after the measurements on day 2,
      each subject performed leg presses that emphasized the eccentric movement for 8
      sets at his six-repetition maximum (6-RM). RESULTS: Compared with baseline, the
      RMR (kJ x d(-1) and kJ x kg FFM(-1) x h(-1) was significantly elevated for RT and
      UT at 24 h and 48 h postexercise. From 24 h to 48 h to 72 h postexercise, RMR
      significantly decreased within both groups. The UT group had a significantly
      higher RMR at 24 h (9,705.4 +/- 204.5 kJ x d(-1)) and 48 h postexercise (8,930.9
      +/- 104.4 kJ x d(-1)) when compared with the RT group (9,209.3 +/- 535.3 and
      8,601.7 + 353.7 kJ x d(-1)). Both [CK] and RPMS showed a similar time course.
      CONCLUSION: There was a significantly higher [CK] for the UT group at 24 h
      postexercise (320.4 +/- 20.1 U x L(-1)) and for both [CK] and RPMS at 48 h
      (1,140.3 +/- 37.1 U x L(-1) and 4.4 +/- 0.5, respectively) and 72 h postexercise
      (675.9 +/- 41.7 U x L(-1) and 1.67 +/- 0.5, respectively) when compared with the
      RT group (24 h, 201.9 +/- 13.4 U x L(-1); 48 h, 845.4 +/- 30.7 U x L(-1) and 3.7
      +/- 0.5: and 72 h postexercise, 420.2 +/- 70.2 U x L(-1) and 0.89 +/- 0.3). These
      data indicate that eccentrically induced muscle damage causes perturbations in
      RMR up to 48 h postexercise.

PMID- 10912883
TI  - Effects of half ironman competition on the development of late potentials.
AB  - OBJECTIVES: The primary purpose was to evaluate the prevalence of late potentials
      (LPs) in triathletes before and after a half ironman triathlon. The secondary
      purpose was to examine whether LPs are the electrocardiographic expression of a
      greater myocardial mass. METHODS: Nine asymptomatic male triathletes (mean age +/
      SD, 32 +/- 5 yr) were examined using signal-averaged ECG (SAECG) 48-72 h before
      (PRE), immediately after (POST), and 24-48 h after the completion (RECOVERY) of a
      half ironman triathlon. Late potentials were considered to be present if two of
      the following SAECG anomalies were observed: 1) a prolonged filtered QRS (/QRS)
      complex (> or = 114 ms), 2) a lengthened low amplitude signal (LAS) duration (>38
      ms), and/or 3) a low root mean square (RMS) voltage of the last 40 ms of the fQRS
      (<20 microV). Left ventricular dimensions were determined at PRE using M-mode
      echocardiography. RESULTS: There were no significant differences between PRE,
      POST, and RECOVERY in the fQRS duration, the LAS duration, or the RMS voltage.
      Two athletes displayed a single SAECG abnormality during PRE and two SAECG
      anomalies (i.e., LPs) during POST. Late potentials remained in one of the two
      athletes during RECOVERY. A moderate relationship existed between fQRS and left
      ventricular mass (r = 0.67, P < 0.05). CONCLUSIONS: Ultra-endurance training
      and/or events do not lead to LPs in the majority of triathletes who do not
      possess ventricular arrhythmias. However, a small subset of triathletes do
      display SAECG anomalies, which are augmented by an ultra-endurance event and may
      persist even after recovery from the event. Left ventricular mass does not affect
      overall SAECG parameters.

PMID- 10912884
TI  - The effect of BCAA supplementation upon the immune response of triathletes.
AB  - INTRODUCTION: Intense long-duration exercise could lead to immune suppression
      through a decrease in the circulating level of plasma glutamine. The decrease in
      plasma glutamine concentration as a consequence of intense long-duration exercise
      was reversed, in some cases, by supplementing the diet of the athletes with
      branched-chain amino acids (BCAA). To better address this question, we have
      evaluated some blood parameters (lymphocyte proliferation, the level of plasma
      cytokines, plasma glutamine concentration, and in vitro production of cytokines
      by peripheral blood lymphocytes) before and after the Sao Paulo International
      Triathlon, as well as the incidence of symptoms of infections between the groups.
      METHODS: Twelve elite male triathletes of mean age 25.5 +/- 3.2 yr (ranging from
      21.4 to 30.1 yr), weighing 74.16 +/- 3.9 kg, swam 1.5 km, cycled 40 km, and ran
      10 km (Olympic triathlon) in the Sao Paulo International Triathlon held in April
      1997 and April 1998. In both events, six athletes received BCAA and the others,
      placebo. RESULTS: Athletes from the BCAA group (BG) presented the same levels of
      plasma glutamine, before and after the trial, whereas those from the placebo
      group showed a reduction of 22.8% in plasma glutamine concentration after the
      competition. Changes in the proliferative response of peripheral blood
      lymphocytes were accompanied by a reduction in IL-1 production after exercise
      (22.2%), which was reversed by BCAA supplementation (20.3%), without changes in
      IL-2 production. DISCUSSION: The data obtained show that BCAA supplementation can
      reverse the reduction in serum glutamine concentration observed after prolonged
      intense exercise such as an Olympic triathlon. The decrease in plasma glutamine
      concentration is paralleled by an increased incidence of symptoms of infections
      that results in augmented proliferative response of lymphocytes cultivated in the
      absence of mitogens. The prevention of the lowering of plasma glutamine
      concentration allows an increased response of lymphocytes to ConA and LPS, as
      well as an increased production of IL-1 and 2, TNF-alpha, and IFN-gamma, possibly
      linked to the lower incidence of symptoms of infection (33.84%) reported by the
      supplemented athletes.

PMID- 10912885
TI  - Expression of the inducible nitric oxide synthase (iNOS) in human leukocytes:
      responses to running exercise.
AB  - INTRODUCTION: We examined the influence of two different bouts of vigorous
      running exercise on the expression of the inducible nitric oxide synthase (iNOS)
      in leukocytes (LE). METHODS: In study 1, 10 trained runners competed in a half
      marathon (HM) lasting 90.5 +/- 11.0 min. In study 2, 8 untrained subjects
      performed a graded treadmill test followed by a continuous run (CR) until
      exhaustion (11.3 +/- 1.3 min). iNOS mRNA levels were assessed by RT/PCR at rest,
      0, 3, and 24 h after HM and CR. In study 2, iNOS was additionally analyzed at the
      protein level in lympho- (L), mono- (M), and granulocytes (G) by flow cytometry
      at rest and up to 48 h after CR. RESULTS: Analysis revealed a rise of the iNOS
      transcript directly after the HM in 8 of 10 subjects. In study 2, the expression
      of iNOS protein at rest differed between L (mean +/- SE: 30.9 +/- 4.5% iNOS
      positive cells), M (91.3 +/- 4.0%), and G (64.9 +/- 10.3%): 3 h after CR,
      expression of iNOS increased in L (67.3 +/- 7.4%) and G (90.3 +/- 2.9%) and was
      still elevated 48 h post-exercise. However, our measurements failed to detect
      significant changes of leukocyte iNOS mRNA in response to CR. After the HM, our
      findings were paralleled by elevated plasma levels of interleukin-8,
      myeloperoxidase (MPO), and partly of TNF-alpha, whereas CR only induced a low
      rise of MPO. CONCLUSION: Our investigations revealed an increased expression of
      iNOS at the transcriptional and translational level in response to vigorous
      exercise. This reflects an inflammatory response and may contribute to an
      exercise-induced rise of endogenous nitric oxide production. It remains unclear
      if these effects serve an in-vivo immunoregulatory or cell-damaging role.

PMID- 10912886
TI  - Growth hormone responses during strenuous exercise: the role of GH-releasing
      hormone and GH-releasing peptide-2.
AB  - PURPOSE AND METHODS: This study was designed to investigate the role of two
      effective releasers of growth hormone (GH): GHRH and GHRP-2 during exercise (EX).
      Eight healthy male subjects (ages: 22 +/- 1.2 (mean +/- SD) yr, BMI: 22.5 +/- 2.2
      kg x m(-2)) were exposed to maximally stimulating dose of 100 microg GHRH iv, and
      200 microg GHRP-2 iv, during incremental EX on a cycle ergometer to exhaustion.
      GH responses after EX alone were compared with the responses after the combined
      administration of the same EX plus GHRH, EX plus GHRP-2, and EX plus GHRH plus
      GHRP-2. Blood samples were obtained in the fasted state at intervals for 2 h
      postexercise and the area under the GH response curve (AUC) was calculated by
      trapezoidal integration. RESULTS: Significant differences (P < 0.003) were
      observed between the AUCs after administration of EX alone (mean +/- SEM): 2,324
      +/- 312 microg x L(-1) 120 min, after EX plus GHRH: 6,952 +/- 1,083, after EX
      plus GHRP-2: 14,674 +/- 2,210, and after the combination EX plus GHRH plus GHRP
      2: 17,673 +/- 1,670. However, AUCs after each combination did not differ
      significantly from those after arithmetical addition of each separate stimulus,
      indicating that the mechanisms of the respective stimuli do not interact. Linear
      regression analysis on mean GH responses between 20 and 30 min after the start of
      EX showed that EX alone and GHRH alone explain about 59% (adj. R2) of the GH
      response to the combination EX plus GHRH. The ratio of the respective regression
      coefficients (GHRH vs EX) was about 2:1 (instead of 1:1), indicating that EX
      seems to potentiate the activity of GHRH. GHRH alone and EX alone also explained
      about 74% of the response to the combination EX plus GHRP-2. In the latter
      response, a synergistic action of GHRP-2 on GHRH could be observed. CONCLUSIONS:
      The data indicate that under strenuous EX conditions, endogenous GHRH activity
      causes a further increase of GH release. A GHRP-2 mediated mechanism in the
      central neuroendocrine regulation acts as a "booster," possibly by stimulating
      the effects of GHRH and/or an unknown hypothalamic factor, as well as by
      stimulating the pituitary GH release directly.

PMID- 10912887
TI  - Specific inspiratory muscle training in well-trained endurance athletes.
AB  - PURPOSE: It has been reported that arterial O2 desaturation occurs during maximal
      aerobic exercise in elite endurance athletes and that it might be associated with
      respiratory muscle fatigue and relative hypoventilation. We hypothesized that
      specific inspiratory muscle training (SIMT) will result in improvement in
      respiratory muscle function and thereupon in aerobic capacity in well-trained
      endurance athletes. METHODS: Twenty well-trained endurance athletes volunteered
      to the study and were randomized into two groups: 10 athletes comprised the
      training group and received SIMT, and 10 athletes were assigned to a control
      group and received sham training. Inspiratory training was performed using a
      threshold inspiratory muscle trainer, for 0.5 h x d(-1) six times a week for 10
      wk. Subjects in the control group received sham training with the same device,
      but with no resistance. RESULTS: Inspiratory muscle strength (PImax) increased
      significantly from 142.2 +/- 24.8 to 177.2 +/- 32.9 cm H2O (P < 0.005) in the
      training but remained unchanged in the control group. Inspiratory muscle
      endurance (PmPeak) also increased significantly, from 121.6 +/- 13.7 to 154.4 +/-
      22.1 cm H2O (P < 0.005), in the training group, but not in the control group. The
      improvement in the inspiratory muscle performance in the training group was not
      associated with improvement in peak VEmax, VO2max breathing reserve (BR). or
      arterial O2 saturation (%SaO2), measured during or at the peak of the exercise
      test. CONCLUSIONS: It may be concluded that 10 wk of SIMT can increase the
      inspiratory muscle performance in well-trained athletes. However, this increase
      was not associated with improvement in aerobic capacity, as determined by VO2max,
      or in arterial O2 desaturation during maximal graded exercise challenge. The
      significance of such results is uncertain and further studies are needed to
      elucidate the role of respiratory muscle training in the improvement of aerobic
      type exercise capacity.

PMID- 10912888
TI  - Effect of rhEPO administration on serum levels of sTfR and cycling performance.
AB  - PURPOSE: We assessed the possibility of using soluble transferrin receptor (sTfR)
      as an indicator of doping with recombinant erythropoietin (rhEPO). METHODS: A
      double-blind, placebo-controlled study was conducted with the administration of
      5,000 U of rhEPO (N = 10) or placebo (N = 10) three times weekly (181-232 U x kg(
      1) x wk-1) for 4 wk to male athletes. We measured hematocrit and the
      concentration of hemoglobin, sTfR, ferritin, EPO, and quantified the effects on
      performance by measuring time to exhaustion and maximal oxygen uptake (VO2max) on
      a cycle ergometer. RESULTS: Hematocrit increased from 42.7 +/- 1.6% to 50.8 +/-
      2.0% in the EPO group, and peaked 1 d after treatment was stopped. In the EPO
      group, there was an increase in sTfR (from 3.1 +/- 0.9 to 6.3 +/- 2.3 mg x L(-1)
      , P < 0.001) and in the ratio between sTfR and ferritin (sTfR-ferritin(-1)) (from
      3.2 +/- 1.6 to 11.8 +/- 5.1, P < 0.001). The sTfR increase was significant after
      1 wk of treatment and remained so for 1 wk posttreatment. Individual values for
      sTfR throughout the study period showed that 8 of 10 subjects receiving rhEPO,
      but none receiving placebo, had sTfR levels that exceeded the 95% confidence
      interval for all subjects at baseline (= 4.6 mg x L(-1)). VO2max increased from
      63.6 +/- 4.5 mL x kg(-1) x min(-1) before to 68.1 +/- 5.4 mL x kg(-1) x min(-1) 2
      d post rhEPO administration (7% increase, P = 0.001) in the EPO group.
      Hematocrit, sTfR, sTfR-ferritin(-1), and VO2max did not change in the placebo
      group. CONCLUSION: Serum levels of sTfR may be used as an indirect marker of
      supranormal erythropoiesis up to 1 wk after the administration of rhEPO, but the
      effects on endurance performance outlast the increase in sTfR.

PMID- 10912889
TI  - Human erythrocyte and plasma amino acid concentrations during exercise.
AB  - PURPOSE: This investigation examined the effects of exercise and maltodextrin
      (Md) or placebo (Pl) ingestion on plasma and erythrocyte concentrations of amino
      acids. METHODS: The erythrocyte and plasma concentrations of 17 amino acids, as
      well as plasma glucose and insulin, were analyzed in eight healthy trained male
      subjects before, during, and 25 min after 90-min cycle ergometer exercise at 65%
      peak oxygen uptake. The two treatments involved ingestion of orange-flavored
      water (Pl) or orange-flavored 10% maltodextrin solution (Md). RESULTS: Two-way
      ANOVA revealed 1) that plasma concentrations of alanine and tyrosine changed
      significantly during the treatments, 2) that the plasma concentrations were
      significantly different between treatments for glycine and threonine, 3) that all
      erythrocyte concentrations increased significantly throughout the treatments
      except for arginine and tyrosine, and 4) that there were no significant
      differences in erythrocyte concentrations between the treatments. Three-way ANOVA
      highlighted the significant differences in the time responses between plasma and
      erythrocyte concentrations; the changes in erythrocyte levels from rest being
      significantly different from plasma for all amino acids except aspartic acid,
      glycine, and ornithine. Plasma glucose concentrations became elevated and
      remained above rest values in Md but fell below rest values in Pl: the
      differences in concentration between treatments were significant.
      Correspondingly, plasma insulin was significantly higher in Md during exercise.
      CONCLUSION: These results highlight that far from being slow in the uptake of
      amino acids, the erythrocyte in fact sequesters amino acids at an appreciable
      rate during exercise without a corresponding elevation in the plasma amino acids.
      For a greater understanding of amino acid changes during exercise, the analysis
      of both plasma and erythrocytes is recommended.

PMID- 10912890
TI  - Tracking physical fitness and physical activity from childhood to adolescence:
      the muscatine study.
AB  - PURPOSE: Physical fitness and physical activity tracking data enhance our
      understanding as to when children settle into their long-term exercise and
      fitness patterns and, therefore. provide insight as to when programs focusing on
      preventing sedentary adults behaviors should be initiated. METHODS: In this
      paper, the tracking of physical fitness and physical activity was examined in a 5
      yr population-based study of children and adolescents in Muscatine, IA. Study
      subjects (N = 126) were pre- or early-pubescent at baseline (mean age boys 10.8
      yr and girls 10.3 yr). Physical fitness was measured using direct determination
      of oxygen uptake and maximal voluntary isometric contraction while physical
      activity was assessed via questionnaire. RESULTS: Boys classified as sedentary
      based on initial measurements of TV viewing and video game playing were 2.2 times
      more likely than their peers to also be classified as sedentary at follow-up.
      Tracking of most physical fitness and physical activity variables was moderate to
      high, indicating some predictability of early measurements for later values.
      Sedentary behavior tracked better in boys, whereas vigorous activity tended to
      track better in girls. CONCLUSION: These observations suggest that preventive
      efforts focused on maintaining physical fitness and physical activity through
      puberty will have favorable health benefits in later years.

PMID- 10912891
TI  - The effect of comments about shoe construction on impact forces during walking.
AB  - Comparisons of ground reaction forces (GRF) during gait are not typically
      conducted with blinding of the varied shoe characteristic, raising concerns
      related to the existence of a placebo effect, or a subject response based on a
      perceived expectation of change. PURPOSE: To determine whether investigator
      comments on shoe construction influenced GRF measures and ratings of shoe
      cushioning during walking. METHODS: 19 female college students volunteered for a
      study presented as a test of a new shoe material. The study involved walking (2.5
      m x s(-1)) under three shoe conditions (SC). Shoes in SC2 and SC3 were harder
      than those in SC1, but shoes in SC1 and SC3 looked similar. Subjects in a mislead
      group (N = 9) were told SC1 and SC3 were baseline measures in a standard shoe,
      with SC2 misleadingly described as a shoe constructed of unique new material. A
      control group performed the same three conditions without investigator
      description. GRF data were collected for 10 trials for each subject in each
      condition, and subjects rated the perceived cushioning of each shoe. GRF data and
      perceived cushioning scores were analyzed using mixed-factor (group by shoe)
      ANOVA. RESULTS: A significant shoe main effect was found for loading rate. Post
      hoc tests identified the difference between SC1 and both SC2 and SC3. The group
      main effect was not significant for any dependent variable. CONCLUSIONS: Results
      suggest that, as a group, GRF data and cushioning scores are not affected by
      investigator comments that do not match shoe construction characteristics.
      However, ratings of perceived shoe cushioning by some individual subjects
      reflected investigator comments and not the vertical GRF variables.

PMID- 10912892
TI  - A three-dimensional biomechanical analysis of sumo and conventional style
      deadlifts.
AB  - PURPOSE: Strength athletes often employ the deadlift in their training or
      rehabilitation regimens. The purpose of this study was to quantify kinematic and
      kinetic parameters by employing a three-dimensional analysis during sumo and
      conventional style deadlifts. METHODS: Two 60-Hz video cameras recorded 12 sumo
      and 12 conventional style lifters during a national powerlifting championship.
      Parameters were quantified at barbell liftoff (LO), at the instant the barbell
      passed the knees (KP), and at lift completion. Unpaired t-tests (P < 0.05) were
      used to compare all parameters. RESULTS: At LO and KP, thigh position was 11-16
      degrees more horizontal for the sumo group, whereas the knees and hips extended
      approximately 12 degrees more for the conventional group. The sumo group had 5-10
      degrees greater vertical trunk and thigh positions, employed a wider stance (70
      +/- 11 cm vs 32 +/- 8 cm), turned their feet out more (42 +/- 8 vs 14 +/- 6
      degrees). and gripped the bar with their hands closer together (47 +/- 4 cm vs 55
      +/- 10 cm). Vertical bar distance, mechanical work, and predicted energy
      expenditure were approximately 25-40% greater in the conventional group. Hip
      extensor, knee extensor, and ankle dorsiflexor moments were generated for the
      sumo group, whereas hip extensor, knee extensor, knee flexor, and ankle plantar
      flexor moments were generated for the conventional group. Ankle and knee moments
      and moment arms were significantly different between the sumo and conventional
      groups, whereas hip moments and moments arms did not show any significantly
      differences. Three-dimensional calculations were more accurate and significantly
      different than two-dimensional calculations, especially for the sumo deadlift.
      CONCLUSIONS: Biomechanical differences between sumo and conventional deadlifts
      result from technique variations between these exercises. Understanding these
      differences will aid the strength coach or rehabilitation specialist in
      determining which deadlift style an athlete or patient should employ.

PMID- 10912893
TI  - Effects of front and dual suspension mountain bike systems on uphill cycling
      performance.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of front
      suspension (FS) and dual suspension (DS) mountain bike designs on time-trial
      performance and physiological responses during uphill cycling on a paved- and off
      road course. METHODS: Six trained male cyclists (35.6 +/- 9 yr, 76.9 +/- 8.8 kg,
      VO2 peak 58.4 +/- 5.6 mL x kg(-1) x min-1)) were timed using both suspension
      systems on an uphill paved course (1.62 km, 183-m elevation gain) and an uphill
      off-road course (1.38 km, 123-m elevation gain). During the field trials, VO2 was
      monitored continuously with a KB1-C portable gas analyzer, and power output with
      an SRM training system. RESULTS: On the paved course, total ride time on FS (10.4
      +/- 0.7 min) and DS (10.4 +/- 0.8 min) was not different (P > 0.05). Similarly,
      total ride time on the off-road course was not significantly different on the FS
      bike (8.3 +/- 0.7 min) versus the DS bike (8.4 +/- 1.1 min). For each of the
      course conditions, there was no significant difference between FS and DS in
      average minute-by-minute VO2, whether expressed in absolute (ABS; L x min(-1)) or
      relative (REL; mL x [kg body wt +/- kg bike wt(-1)] x min(-1) values. Average
      power output (W) was significantly lower for ABS FS versus DS (266.1 +/- 61.6 W
      vs 341.9 +/- 61.1 W, P < 0.001) and REL FS versus DS (2.90 +/- 0.55 W x kg(-1) vs
      3.65 +/- 0.53 W x kg(-1), P < 0.001) during the off-road trials. Power output on
      the paved course was also significantly different for ABS FS versus DS (266.6 +/-
      52 W vs 345.4 +/- 53.4 W, P < 0.001) and REL FS versus DS (2.99 +/- 0.55 W x kg(
      1) vs 3.84 +/- 0.54 W x kg(-1), P < 0.001). CONCLUSION: We conclude that despite
      significant differences in power output between FS and DS mountain bike systems
      during uphill cycling, these differences do not translate into significant
      differences in oxygen cost or time to complete either a paved- or off-road
      course.

PMID- 10912894
TI  - Cadence, power, and muscle activation in cycle ergometry.
AB  - PURPOSE: Based on the resistance-rpm relationship for cycling, which is not
      unlike the force-velocity relationship of muscle, it is hypothesized that the
      cadence which requires the minimal muscle activation will be progressively higher
      as power output increases. METHODS: To test this hypothesis, subjects were
      instrumented with surface electrodes placed over seven muscles that were
      considered to be important during cycling. Measurements were made while subjects
      cycled at 100, 200, 300, and 400 W at each cadence: 50, 60, 80, 100, and 120 rpm.
      These power outputs represented effort which was up to 32% of peak power output
      for these subjects. RESULTS: When all seven muscles were averaged together, there
      was a proportional increase in EMG amplitude each cadence as power increased. A
      second-order polynomial equation fit the EMG:cadence results very well (r2 = 0.87
      0.996) for each power output. Optimal cadence (cadence with lowest amplitude of
      EMG for a given power output) increased with increases in power output: 57 +/-
      3.1, 70 +/- 3.7, 86 +/- 7.6, and 99 +/- 4.0 rpm for 100, 200, 300, and 400 W,
      respectively. CONCLUSION: The results confirm that the level of muscle activation
      varies with cadence at a given power output. The minimum EMG amplitude occurs at
      a progressively higher cadence as power output increases. These results have
      implications for the sense of effort and preferential use of higher cadences as
      power output is increased.

PMID- 10912895
TI  - Arm and leg power output in swimmers during simulated swimming.
AB  - PURPOSE: Previously, it has not been possible to compare power output of the arms
      and legs during simulated swimming using dry-land ergometry. The purpose of this
      study was to determine arm-pulling and leg-kicking power using isokinetic dry
      land ergometry. METHODS: Twenty-two highly trained male swimmers of mean (+/- SD)
      age, 23 +/- 3.6 yr; body mass, 78 +/- 5.9 kg; and stature, 1.79 +/- 0.04 m were
      recruited to the study. First, subjects performed 10 s of all-out exercise at
      each of five resistance settings, with 1 h rest in between, to determine the best
      maximal pull velocity (MPVopt). Second, they performed an all-out 30-s test at
      MPVopt, which was repeated the following day. These repeated 30-s tests were
      performed separately using simulated front-crawl arm-pulling and leg-kicking, on
      a computer-interfaced swim bench and purpose-built leg-kicking ergometer. Peak
      and mean power output (PPO; MPO) were determined from regression analysis of the
      power vs time relationship. RESULTS: The mean (+/- SEM) PPO for arms and legs
      were 304 +/- 22 W versus 435 +/- 36 W. For MPO, the means were 225 +/- 31 W vs
      312 +/- 26 W, respectively. These values were attained at mean MPVopt of 2.5 +/-
      0.2 m x s(-l) for arms and 2.3 +/- 0.4 m x s(-1) for legs. The variation in PPO
      from repeated testing was 7.3% for arms and 8.3% for legs. CONCLUSIONS: These
      results show that the legs can sustain greater power output than the arms during
      simulated swimming. Also, the intra-subject variation in measurement of power
      output is small using these dry-land ergometers. These methods of assessment
      might be useful in explaining swimming performance and in monitoring changes that
      take place during training.

PMID- 10912896
TI  - Performance of plantar flexor muscles with eccentric and isometric contractions
      in intact rats.
AB  - PURPOSE: To examine the changes in performance of active plantar flexor muscles
      of rats by controlled dorsiflexion (i.e., stretching of muscles) at two angular
      velocities. METHODS: Repeated stretches (30) at two velocities of ankle rotation
      [slow stretch (0.87 rads x s(-1) (i.e., 50 degrees x (s-1))), fast stretch (10.47
      rad x s(-1) (i.e., 600 degrees x s-1))] were superimposed on maximally active
      muscles from an ankle position of 1.57 rad to 0.70 rad (i.e., from 90 degrees to
      40 degrees). Repeated isometric contractions (30) of the same duration (1,900 ms)
      and rest interval (3 min) were performed at 1.13 rad (i.e., 65 degrees).
      Performance was assessed by measuring the isometric torque at ankle positions of
      1.57 and 0.70 rad, work during concentric contractions [range of motion 1.22 rad
      (i.e., 70 degrees)], and the time to produce 50% of the maximal isometric torque.
      RESULTS: Thirty isometric contractions resulted in a linear reduction in torque
      (total deficit of 13.8% at 1.57 rad), whereas for slow and fast stretches, half
      of the total, nonlinear deficit at 1.57 rad (about 30%) was completed after six
      stretches. Increases in half contraction times were larger for stretches than for
      isometric contractions. Reductions in isometric torque were greater at an ankle
      position of 1.57 rad than at 0.70 rad. One hour of rest after the repeated
      stretches and isometric contractions did not restore muscle performance.
      CONCLUSIONS: Isometric contractions of skeletal muscle can create a torque
      deficit which is much less than that after stretches. Repeated fast and slow
      stretches resulted in similar torque deficits which did not recover after a rest
      period of 1 h.

PMID- 10912897
TI  - Effect of salbutamol on muscle strength and endurance performance in nonasthmatic
      men.
AB  - PURPOSE: The ergogenic effect of acute beta2-adrenergic agonist administration in
      nonasthmatic individuals has not been clearly demonstrated. Therefore, the acute
      effects of oral administration of the beta2-adrenergic agonist salbutamol (4 mg)
      on muscle strength and endurance performance were studied in 16 nonasthmatic men
      in a double-blind randomized cross-over study. METHODS: Peak expiratory flow
      (Mini Wright Peakflowmeter), isokinetic strength of the knee extensors and knee
      flexors at four angular velocities (Cybex II dynamometer), and endurance
      performance in a cycle ergometer test until exhaustion at 70% of maximal workload
      were measured. RESULTS: Peak expiratory flow increased from 601 +/- 67 L x min(
      1) to 629 +/- 64 L x min(-1) after salbutamol (P < 0.05). Peak torque was higher
      after salbutamol than after placebo (4.4% for the knee extensors, 4.9% for the
      knee flexors) (P < 0.05). Mean endurance time increased from 3,039 +/- 1,031 s
      after placebo to 3,439 +/- 1,287 s after salbutamol (P = 0.19). When four
      subjects complaining about adverse side effects were excluded from the analysis,
      the increase in endurance time (729 +/- 1,007 s or 29%) was statistically
      significant (P <-0.05). Salbutamol did not affect VO2, respiratory exchange
      ratio, heart rate, and plasma free fatty acid and glycerol concentration during
      exercise; plasma lactate and potassium concentrations were increased (P < 0.05).
      CONCLUSIONS: Under the conditions of this study, oral salbutamol appears to be an
      effective ergogenic aid in nonasthmatic individuals not experiencing adverse side
      effects.

PMID- 10912898
TI  - Evaluation of the strength-size relationship in vivo using various muscle size
      indices.
AB  - PURPOSE: It is well accepted that maximum strength is related to muscle size. The
      primary purpose of this study was to determine whether anthropometric or dual
      energy x-ray absorptiometry (DEXA) estimates of muscle size were valid predictors
      of plantar flexor maximum voluntary contraction (MVC) strength and could be used
      in lieu of more sophisticated techniques (e.g., magnetic resonance imaging
      (MRI)). Additionally, we compared the relationship among MVC and three MRI
      determined muscle size measures; anatomical (ACSA) and physiological (PCSA) cross
      sectional areas; and muscle volume (VOLm). METHODS: We measured plantar flexor
      MVC at 1.83 rad and various indices of muscle size: 1) body weight, 2) total body
      lean mass (LM) (DEXA), 3) lower leg LM (DEXA), 4) lower leg circumference, 5)
      estimated muscle+bone cross-sectional area (CSA) from circumference and calf skin
      fold, 6) triceps surae ACSA, 7) triceps surae PCSA, and (8) triceps surae volume
      (VOLm), in 39 premenopausal women (mean +/- SD: 36 +/- 8 yr, 165 +/- 6 cm, and 65
      +/- 9 kg). RESULTS: Zero-order correlations showed significant (P < 0.05)
      associations between MVC and total body LM (r = 0.365), lower leg LM (r = 0.381),
      circumference (r = 0.584), estimated muscle+bone CSA (r = 0.447), ACSA (r =
      0.733), PCSA (r = 0.715), and VOLm (r = 0.649). By using the Fisher Z
      transformation, ACSA and PCSA correlated significantly higher with MVC (P < 0.05)
      than anthropometric and DEXA indices. Further, only ACSA and PCSA regressed to
      the origin, indicating the ability to predict MVC was greatest with these two
      measures. CONCLUSIONS: The MRI-determined muscle size indices, which were
      specific to the triceps surae, correlated with strength better than whole limb
      anthropometric and DEXA indices. In this group of women, both ACSA and PCSA
      appeared superior to VOLm for predicting strength. PCSA was not found to be more
      precise than ACSA. ACSA appears to provide adequate precision for estimating
      plantar flexor specific tension in vivo.

PMID- 10912899
TI  - Fatigue after submaximal intensive stretch-shortening cycle exercise.
AB  - OBJECTIVE: The aim of the present study was to examine some sites of
      neuromuscular fatigue after submaximal intensity stretch-shortening cycle
      exercise. METHODS: Twelve male subjects performed consecutive sledge jumps at 60%
      of maximal height until exhaustion (mean duration 443.7 s +/- 304.9 s, mean +/-
      SD). RESULTS: During the exercise, the blood lactate increased from 1.8 +/- 0.6
      mmol x L(-1) (before exercise) to 6.1 +/- 1.7 mmol x L(-1) (P < 0.001) and serum
      creatine-kinase from 248 +/- 142 IU x L(-1) to 584 +/- 344 IU x L(-1) (P <
      0.001). Electrical stimulation of the vastus lateralis and quadriceps femoris
      muscles to induce isometric knee extension resulted in decreased peak torque
      during single and double twitch after workout (from 22.1 +/- 6.3 Nm to 17.3 +/-
      8.0 Nm, P < 0.05, and from 96.6 +/- 15.4 Nm to 76.2 x 19.8 Nm, P < 0.001,
      respectively), whereas there were no significant changes in contraction and
      relaxation times. Torque during 20-Hz stimulation decreased significantly (from
      23.7 +/- 9.2 to 16.1 +/- 7.8 Nm, P < 0.01) but not at 100-Hz stimulation. During
      maximal voluntary isometric knee extensions, the rate of torque development was
      significantly (P < 0.01) more impaired than maximal torque (from 1619 +/- 390 Nm
      x s(-1) to 1,004 +/- 360 Nm x s(-1) and from 185 +/- 30.7 Nm to 151 +/- 32.3 Nm,
      respectively, both P < 0.001). At the same time, the muscle activation level
      increased by 15.8 +/- 24.1% (P < 0.05). The mean EMG amplitude of vastus
      lateralis during MVC increased by 34.9 +/- 39.2% (P > 0.05). CONCLUSION: It was
      concluded that after submaximal stretch-shortening exercise, the low-frequency
      fatigue occurred, very likely caused by lower Ca2+ release per single action
      potential.

PMID- 10912900
TI  - Comparisons of four methods of estimating physical activity in adult women.
AB  - PURPOSE: To compare four different methods of measuring physical activity (PA) in
      adult women under free-living conditions. METHODS: Twelve women participated in a
      7-d period during which PA was assessed via self-report, accelerometry and step
      counting. Subjects wore at the waist a Tritrac-R3D accelerometer, a Computer
      Science Application Inc. activity monitor (CSA), both of which measure bodily
      accelerations in various planes, and a Yamax Digi-Walker-500 that records steps.
      After the 7-d period subjects responded to a 7-d Physical Activity Recall
      interview (PAR). RESULTS: Physical activity-related energy expenditure (PAEE)
      determined from PAR was significantly higher than PAEE estimated from either the
      Tritrac, CSA, or the Yamax data. Time spent in light, moderate, and hard physical
      activity was not significantly different between PAR, CSA, and Tritrac. Log
      transformed activity counts from CSA were highly correlated with log-transformed
      Tritrac results (r > 0.90). Number of steps recorded by the Yamax was
      significantly correlated with untransformed Tritrac and CSA results. CONCLUSIONS:
      Based upon comparisons with PAR, Tritrac, CSA, and Yamax underestimate the amount
      of PAEE by 25, 46, and 48%, respectively. The correspondence between the Tritrac
      and CSA results suggests that both devices produce similar estimates of bodily
      movement in free-living women. The relationships among results for Tritrac, CSA,
      and Yamax indicate that the number of steps recorded by the Yamax is
      representative of the amount of physical activity performed during the day as
      estimated by Tritrac and CSA. These results should be useful when selecting a
      method to measure PA in individuals under free-living conditions.

PMID- 10912901
TI  - Evaluation of the kaiser physical activity survey in women.
AB  - PURPOSE: The Kaiser Physical Activity Survey (KPAS) was evaluated for test-retest
      reliability and comparison with direct and indirect measures of physical activity
      (PA) in 50 women (ages 20-60 yr) with a broad range of physical activity (PA)
      habits. METHODS: The KPAS, an adaptation of the Baecke usual physical activity
      survey, was designed specifically to assess activity in women. It provides four
      summary activity indexes: housework/caregiving, active living habits, sports, and
      occupation. Summary indexes were compared against direct (Caltrac accelerometer
      and PA records) and indirect (cardiorespiratory fitness (VO2 peak) and percent
      body fat) criterion measures of PA. Participants kept detailed PA records for
      two, 7-d periods, separated by 1 month. Caltrac accelerometers were worn
      concurrently with the PA records. RESULTS: Intraclass correlations for 1-month
      test-retest reliability were high for all KPAS indexes (r = 0.79 to 0.91, P <
      0.01). Age-adjusted Spearman rho correlations between the KPAS sports/exercise
      and active living habits indexes were of moderate magnitude for VO2 peak (r =
      0.34 to 0.76, P < 0.01) and percent body fat (r = -.30 to -0.59, P < 0.05). KPAS
      caregiving and occupation indexes were related to Caltrac kcal x d(-1) (r = 0.30
      to 0.44, P < 0.05). Correlations between similar activities from the KPAS and PA
      records ranged from r = 0.03 to 0.64. Daily, habitual activities from the KPAS
      and PA records had the highest correlations (r > 0.28). Correlations among
      infrequent activities were lower (r < 0.05). CONCLUSION: The KPAS demonstrated
      good reliability and was reasonably accurate in detecting regular
      housework/caregiving, occupation, sports/exercise, and active leisure activities
      among women with a broad range of physical activity habits.

PMID- 10912902
TI  - Validation of air displacement plethysmography for assessing body composition.
AB  - PURPOSE: The purpose of this study was to verify the validity of an air
      displacement plethysmography device (Bod Pod) for estimating body density (Db).
      METHODS: The Db from the Bod Pod (DbBP) was compared with the Db from hydrostatic
      weighing (DbHW) at residual lung volume in a heterogeneous sample of 30 black men
      who varied in age (32.0 +/- 7.7 yr), height (180.3 +/- 7.5 cm), body mass (84.2
      +/- 15.0 kg), body fatness (16.1 +/- 7.5%), and self-reported physical activity
      level and socioeconomic status. The Db for each method was converted to relative
      body fat (%BF) using race-specific conversion formulas and subsequently compared
      with %BF obtained from dual-energy x-ray absorptiometry (%BFDXA). RESULTS: Linear
      regression, using DbHW as the dependent variable and DbBP as the predictor,
      produced an R2 = 0.84 and SEE = 0.00721 g x cc(-1). However, the mean difference
      between the two methods (0.00450 +/- 0.00718 g x cc(-1) was significant (P <
      0.01). The Bod Pod underestimated the Db of 73% of the sample. The %BF estimates
      from the Bod Pod, HW, and DXA differed significantly (P < 0.01). The average
      %BFBP (17.7 +/- 7.4%) was significantly greater than %BFHW (15.8 +/- 7.5%) and
      %BFDXA (16.1 +/- 7.5%); however, there was no significant difference between
      %BFHW and %BFDXA. CONCLUSION: The Bod Pod significantly and systematically
      underestimated Db, resulting in an overestimation of %BF. More cross-validation
      research is needed before recommending the Bod Pod as a reference method.

PMID- 10912903
TI  - American College of Sports Medicine position stand. Exercise and type 2 diabetes.
AB  - Physical activity, including appropriate endurance and resistance training, is a
      major therapeutic modality for type 2 diabetes. Unfortunately, too often physical
      activity is an underutilized therapy. Favorable changes in glucose tolerance and
      insulin sensitivity usually deteriorate within 72 h of the last exercise session:
      consequently, regular physical activity is imperative to sustain glucose-lowering
      effects and improved insulin sensitivity. Individuals with type 2 diabetes should
      strive to achieve a minimum cumulative total of 1,000 kcal x wk(-1) from physical
      activities. Those with type 2 diabetes generally have a lower level of fitness
      (VO2max) than nondiabetic individuals. and therefore exercise intensity should be
      at a comfortable level (RPE 10-12) in the initial periods of training and should
      progress cautiously as tolerance for activity improves. Resistance training has
      the potential to improve muscle strength and endurance, enhance flexibility and
      body composition, decrease risk factors for cardiovascular disease, and result in
      improved glucose tolerance and insulin sensitivity. Modifications to exercise
      type and/or intensity may be necessary for those who have complications of
      diabetes. Individuals with type 2 diabetes may develop autonomic neuropathy,
      which affects the heart rate response to exercise, and as a result, ratings of
      perceived exertion rather than heart rate may need to be used for moderating
      intensity of physical activity. Although walking may be the most convenient low
      impact mode, some persons, because of peripheral neuropathy and/or foot problems,
      may need to do non-weight-bearing activities. Outcome expectations may contribute
      significantly to motivation to begin and maintain an exercise program.
      Interventions designed to encourage adoption of an exercise regimen must be
      responsive to the individual's current stage of readiness and focus efforts on
      moving the individual through the various "stages of change."

PMID- 10912904
TI  - The ethics of not testing in athletic competition.

PMID- 10912905
TI  - Soluble neutral metallopeptidases: physiological regulators of peptide action.
AB  - Classically, the pre- and post-secretory processing of peptide signals appears to
      be mediated primarily by subtilisin-like peptidases in secretory vesicles and/or
      membrane-associated neutral endopeptidases in the extracellular environment. This
      article presents both biochemical and physiological evidence to support a role
      for soluble neutral metallopeptidases in the mediation of cell-to-cell
      communication by the selective generation and termination of peptide signals.
      These soluble peptidases have been implicated in the normal and disease-state
      processing of peptides involved in neurological, endocrine and cardiovascular
      functions. In this context, specific inhibitors of these enzymes could
      selectively modulate peptide levels and thus have considerable therapeutic
      potential. The aim of this review is to discuss the design and development of
      specific inhibitors of soluble neutral metallopeptidases that have been
      instrumental in identifying the roles of these enzymes. It will also review the
      evidence and present a case for the involvement of soluble neutral
      metallopeptidases in the regulation of peptide signalling in both central nervous
      system (CNS) and peripheral tissues.

PMID- 10912906
TI  - The deprotection of Lys(Mtt) revisited.
AB  - The selective deprotection of Lys(Mtt)-containing peptidyl resins was
      successfully monitored by RP-HPLC using very short linear gradients. RP-HPLC
      analyses of the acidic filtrates also revealed the partial cleavage of the Trt
      groups and of the peptide-resin bond. The absorbance of the Mtt carbocation at
      470 nm is only twice that of the Trt cation. Thus, the UV monitoring at 470 nm
      seems to be inappropriate, especially at the end of the deprotection, when the
      Mtt and the Trt levels are comparable.

PMID- 10912907
TI  - Required structure of cationic peptide for oligonucleotide-binding and 
      delivering into cells.
AB  - Improvement of the methods for oligonucleotide delivery into cells is necessary
      for the development of antisense therapy. In the present work, a new strategy for
      oligonucleotide delivery into cells was tested using cationic peptides as a
      vector. At first, to understand what structure of the peptide is required for
      binding with an oligonucleotide, several kinds of alpha-helical and non-alpha
      helical peptides containing cationic amino acids were employed. As a result, the
      amphiphilic alpha-helix peptides were best for binding with the oligonucleotide,
      and the long chain length and large hydrophobic region in the amphiphilic
      structure of the peptide were necessary for the binding and forming of aggregates
      with the oligonucleotide. In the case of non-alpha-helical peptides, no
      significant binding ability was observed even if their chain lengths and number
      of cationic amino acid residues were equal to those of the alpha-helical
      peptides. The remarkable ability of oligonucleotide delivery into COS-7 cells was
      observed in the alpha-helical peptides with a long chain length and large
      hydrophobic region in the amphiphilic structure, but was not observed in the non
      alpha-helical peptides. It is considered that such alpha-helical peptides could
      form optimum aggregates with the ODN for uptake into cells. Based on these
      results, the alpha-helical peptide with a long chain length and large hydrophobic
      region is applicable as a vector for the delivery of oligonucleotides into cells.

PMID- 10912908
TI  - Optically active aromatic amino acids. Part VI. Synthesis and properties of
      (Leu5)-enkephalin analogues containing O-methyl-L-tyrosine1 with ring
      substitution at position 3'.
AB  - Twelve new [Tyr(Me)1, Leu5]-enkephalin analogues with substituents at position 3'
      of the Tyr ring have been synthesized using traditional solution methods. The
      substituents were -CO2H, -CONH2, -CO2Me, -(E)-CH=NOH, -(E)-CH=NOMe and CH2OH. The
      analogues were C-terminated with methyl esters, amides or as free acids. In the
      in vitro biological assays a remarkable agonist activity to the opiate receptor
      mu in guinea pig ileum (GPI) relative to Leu-ENK was shown by the following: Leu
      ENK, 100; [Tyr(Me)(3'-CO2Me)1, Leu-OMe5]-ENK (I), 8.1; [Tyr(Me)(3'-(E)-CH=NOH)1,
      Leu-OMe5]-ENK (VI), 26.2; [Tyr(Me)(3'-(E)-CH=NOH)1, Leu-OH5]-ENK (VII), 2.9;
      [Tyr(Me)(3'-(E)-CH=NOH)1, Leu-NH2(5)]-ENK (VIII), 4.7; and [Tyr(Me)(3'-CH2OH)1,
      Leu-OMe5]-ENK (X), 5.6. The agonist effect was naltrexone- or naloxone
      reversible. The masking of the hydroxyl group in (E)-hydroxyiminomethyl group of
      analogue (VI) by O-methylation has totally abolished its GPI agonist activity. It
      seems that the (E)-CH=NOH group shows affinity and plays an analogous role to the
      phenol group Tyr1 in leucine-enkephalin and in the tyramine group of the opiate
      alkaloids. The analogues: [Tyr(Me)(3'-CO2Me)1, Leu-OMe5]-ENK (I), [Tyr(Me)(3'
      CO2H)1, Leu-OMe5]-ENK (II), [Tyr(Me)(3'-CO2Me)1, Leu-NH2(5)]-ENK (III),
      [Tyr(Me)(3'-CO2H)1, Leu-NH2(5)]-ENK (IV), [Tyr(Me)(3'-CONH2)1, Leu-NH2(5)]-ENK
      (V), [Tyr(Me)(3'-(E)-CH=NOH)1, Leu-OMe5]-ENK (VI), [Tyr(Me)(3'-(E)-CH=NOH)1, Leu
      OH5]-ENK (VII), [Tyr(Me)(3'-(E)-CH=NOH)1, Leu-NH2(5)]-ENK (VIII), [Tyr(Me)(3'-(E)
      CH=NOMe)1, Leu-OMe5]-ENK (IX), [Tyr(Me)(3'-CH2OH)1, Leu-OMe5]-ENK (X),
      [Tyr(Me)(3'-CH2OH)1, Leu-OH5]-ENK (XI) and [Tyr(Me)(3'-CH2OH)1, Leu-NH2(5)]-ENK
      (XII) under testing had no significant agonist activity to the enkephalinergic
      receptor in mouse vas deferens (MVD). All methyl esters of synthesized analogues
      of [Leu5]-ENK showed higher activity to mu receptors than structurally identical
      C-terminal amides. It is a surprising result since usually C-terminate amides are
      stronger agonists than C-terminate esters.

PMID- 10912910
TI  - Effects of cyanide and deoxyglucose on Ca2+ signalling in macrovascular
      endothelial cells.
AB  - 1. We have studied the effects of the metabolic inhibitors cyanide (CN) and
      deoxyglucose (DG) on the intracellular Ca2+ concentration ([Ca2+]i) in
      macrovascular endothelial cells derived from human umbilical vein (EA cells). 2.
      CN- and DG increased [Ca2-]i in non-voltage clamped cells. This effect was
      dependent on extracellular Ca2+ concentration and membrane potential, indicating
      that CN- induced a Ca2+ entry. 3. During expose to CN- and/or DG, EA cells
      depolarise. This depolarisation is sometimes preceded by a small, but transient
      hyperpolarisation due to activation of a big - conductance K+ channels, BKCa,
      present in EA cells. However, in approximately 90% of the cells tested, the CN-
      and/or DG induced elevation of [Ca2+]i was insufficient to activate BKCa. 4. CN-
      and/or DG enhanced BKCa currents preactivated by an elevation of [Ca2+]i via cell
      dialysis with 0.5 and 1 microM, respectively. Thus, metabolic inhibition
      sensitises BKCa. 5. The CN- induced depolarisation of EA cells occurs by
      activating a current that reversed at positive membrane potentials. Substituting
      extracellular cations abolished the inward component of this current by NMDG,
      indicating that CN- activated a non-selective cation channel, NSC. This current
      was reduced by extracellular Ca2+ and Mg2'+ but is partially carried by Ca2+. 6.
      It is concluded that CN elevates [Ca2+]i by activating Ca2+ permeable NSC
      channels. The properties of these channels are similar to those of the recently
      described trp3 channels expressed in endothelium.

PMID- 10912909
TI  - Carbopeptides: chemoselective ligation of peptide aldehydes to an aminooxy
      functionalized D-galactose template.
AB  - Multifunctional, topological template molecules such as linear and cyclic
      peptides have been used for the attachment of peptide strands to form novel
      protein models of, for example, 4-alpha-helix bundles. The concept of
      carbohydrates as templates for de novo design of potential protein models has
      been previously described and these novel chimeric compounds were termed
      carbopeptides. Here, a second generation strategy in which carbopeptides are
      synthesized by chemoselective ligation of a peptide aldehyde to an aminooxy
      functionalized alpha-D-galactopyranoside is described. This template was prepared
      by per-O-acylation of methyl alpha-D-galactopyranoside with N,N-Boc2
      aminooxyacetic acid to form a tetra-functionalized template, followed by
      treatment with TFA-CH2Cl2 to release the aminooxy functionality. The peptide
      aldehydes Fmoc-Ser-Gly-Gly-H and H-Ala-Leu-Ala-Lys-Leu-Gly-Gly-H were synthesized
      by a BAL strategy. Four identical copies of peptide aldehyde were smoothly
      attached to the template by chemoselective ligation to form a 2.1 and a 2.9 kDa
      carbopeptide, respectively.

PMID- 10912911
TI  - Changes of endothelial nitric oxide synthase level and activity during
      endothelial cell proliferation.
AB  - The goal of this study was to investigate the effect of endothelial cell
      proliferation on the expression and activity of endothelial nitric oxide synthase
      (eNOS). Bovine atrial endothelial cells (BAtEC) were studied between day 1 and 6
      after seeding. During this period the number of cells in S-phase decreased
      progressively, while cell number and protein content increased, reaching a
      maximum at confluence (day 4). Expression of eNOS (determined by ELISA) and eNOS
      activity (determined by L-arginine to L-citrulline conversion) increased with
      culture duration with a maximum at confluence. Nitric oxide (*NO) release from
      BAtEC was determined after stimulation with Ca2+ ionophore A23187 (10 microM, 30
      min) by .NO chemiluminescence in the absence of a chemical reduction system.
      Total *NO release (measured in the presence of 100 U/ml superoxide dismutase) did
      not change with state of cell proliferation/growth, whereas "bioavailable" *NO
      (measured in the absence of superoxide dismutase) was low in highly proliferating
      BAtEC. Relative eNOS activity (.NO and L-citrulline production per eNOS protein)
      was highest in proliferating BAtEC. The novel finding of this study is that the
      specific eNOS activity is upregulated in proliferating BAtEC and downregulated in
      quiescent BAtEC. The amount of "bioavailable" *NO is determined by eNOS activity
      and *NO inactivation (probably by superoxide), both high in proliferating BAtEC.

PMID- 10912912
TI  - Human vascular and cardiac endothelia express mu opiate receptor transcripts.
AB  - Pharmacologic and immunologic evidence suggests that nitric oxide-coupled mu
      subtype opiate receptors are expressed in human vascular endothelium. In this
      study, we present molecular evidence of mu opiate receptor expression. Using
      primers derived from the human neuronal mu1 opiate receptor, we used RT-PCR to
      detect expression of mu transcripts from human endothelia. Sequence analysis of
      the RT-PCR products revealed 100% identity with the neuronal human mu1 receptor.
      We further show that pretreatment of human internal thoracic artery and cardiac
      atrial endothelium with the proinflammatory cytokines interleukin-1-alpha and 
      beta led to a significant increase in both the expression of the mu transcript
      and in morphine-stimulated nitric oxide release measured amperometrically. Taken
      together, these studies provide molecular evidence that mu-type opiate receptors
      are expressed in human vascular endothelia and that their expression can be
      upregulated by proinflammatory cytokines.

PMID- 10912913
TI  - Cyclic GMP-mediated macromolecular extravasation from angiogenic microvessels in
      vivo.
AB  - Previously, we reported an abrupt reduction in chick chorioallantoic membrane
      (CAM) microvascular permeability to macromolecules between days 4.5 and 5.0 of
      the 21-day gestation. Further, exogenous activation of the cAMP pathway at day
      4.5 served to restrict normal macromolecular extravasation. Here, we evaluated
      the influence of the cGMP pathway on macromolecular efflux at day 5.0. Zaprinast
      (10(-4) M), a selective inhibitor of the cGMP-specific phosphodiesterase (PDE V),
      acutely increased basal levels of FITC-dextran 40 extravasation. Further, the
      cGMP analogue, 8 br-cGMP (10(-4) and 10(-3) M) and the soluble guanylate cyclase
      activator, sodium nitroprusside (SNP, 10(-5) and 10(-4) M) increased tracer
      extravasation in a dose-dependent fashion. The cGMP-mediated increase was not
      associated with gap formation along the junctional clefts, however, vesiculo
      vacuolar structures were characteristic of CAM endothelial ultrastructure. KT
      5823 (10(-5) M), the highly selective protein kinase G (PKG) inhibitor, also
      served to increase basal tracer extravasation. The nonselective PDE inhibitor,
      IBMX (10(-4) M) had no effect alone, but reduced the permeability effects of both
      8 br-cGMP and SNP. Rolipram (10(-4) M), a selective PDE IV inhibitor, on the
      other hand, potentiated the effect of 8 br-cGMP. These results serve to suggest
      that cAMP degradation, rather than PKG activation, is a principal component of
      the cGMP-mediated increase in CAM endothelial permeability in vivo.

PMID- 10912915
TI  - Spinal cord compression injury in the mouse: presentation of a model including
      assessment of motor dysfunction.
AB  - The purpose of this study was to develop a spinal cord injury model in the mouse.
      Various degrees of extradural compression were used to induce mild, moderate or
      severe compression injuries. Furthermore, a locomotor rating scale was developed
      by which the functional outcome of the spinal cord injury could be assessed. The
      introduction of such a model will be useful for further studies on the
      pathogenesis and treatment strategies of spinal cord injury. To assess hindlimb
      motor function, a 10-point scale was used. Initially, the animals were allowed to
      move freely in an open field and were rated 0-5, 0 being no movement and 5 being
      almost normal. Animals scoring a 5 were then assessed using steel bars with
      decreasing widths from 2 cm to 5 mm. For each bar successfully crossed over, they
      gained additional points. Before injury the hindlimb motor function score (MFS)
      in all the animals was 10. In mice with mild compression, MFS was decreased
      slightly on day 1 and recovered to 9 +/- 0.6 on day 14. For mice with moderate
      compression, the MFS decreased to 4.6 +/- 0.4 on day 1 after injury and gradually
      improved to 8.1 +/- 0.6 on day 14. Severe injury resulted in paraplegia of the
      hindlimbs day 1 after injury with a score of 0.6 +/- 0.2. By day 14 after injury,
      these animals gradually recovered to 3.9 +/- 0.1, could bear the weight on the
      hindlimbs and walk with a severe deficit. There was a 3%, 9% and 19% decrease in
      the total cross-sectional area of the spinal cord 14 days after mild, moderate
      and severe injury, respectively. Microtubule-associated protein immunostaining
      revealed that the gray matter decreased to 61 +/- 7% in moderately injured
      animals, while severe compression resulted in a complete loss of gray matter.
      White matter decreased to 86 +/- 6% in moderately injured animals and 29 +/- 11%
      in severely injured animals. This study shows that the mouse can be used to
      achieve reproducible spinal cord compression injuries of various degrees of
      severity. The force of the impact correlates well with the neurological and light
      microscopic outcome. The motor function test presented in this paper and the
      computerized quantification of tissue damage can be used to evaluate the efficacy
      of different treatment strategies.

PMID- 10912914
TI  - Senile dementia associated with amyloid beta protein angiopathy and tau
      perivascular pathology but not neuritic plaques in patients homozygous for the
      APOE-epsilon4 allele.
AB  - Amyloid beta protein deposition in cortical and leptomeningeal vessels, causing
      the most common type of cerebral amyloid angiopathy, is found in sporadic and
      familial Alzheimer's disease (AD) and is the principal feature in the hereditary
      cerebral hemorrhage with amyloidosis, Dutch type. The presence of the
      Apolipopriotein E (APOE)-epsilon4 allele has been implicated as a risk factor for
      AD and the development of cerebral amyloid angiopathy in AD. We report clinical,
      pathological and biochemical studies on two APOE-epsilon4 homozygous subjects,
      who had senile dementia and whose main neuropathological feature was a severe and
      diffuse amyloid angiopathy associated with perivascular tau neurofibrillary
      pathology. Amyloid beta protein and ApoE immunoreactivity were observed in
      leptomeningeal vessels as well as in medium-sized and small vessels and
      capillaries in the parenchyma of the neocortex, hippocampus, thalamus,
      cerebellum, midbrain, pons, and medulla. The predominant peptide form of amyloid
      beta protein was that terminating at residue Val40, as determined by
      immunohistochemistry, amino acid sequence and mass spectrometry analysis. A crown
      of tau-immunopositive cell processes was consistently present around blood
      vessels. DNA sequence analysis of the Amyloid Precursor Protein gene and
      Presenilin-1 (PS-1) gene revealed no mutations. In these APOE-epsilon4 homozygous
      patients, the pathological process differed from that typically seen in AD in
      that they showed a heavy burden of perivascular tau-immunopositive cell processes
      associated with severe amyloid beta protein angiopathy, neurofibrillary tangles,
      some cortical Lewy bodies and an absence of neuritic plaques. These cases
      emphasize the concept that tau deposits may be pathogenetically related to
      amyloid beta protein deposition.

PMID- 10912916
TI  - Multiple mitochondrial DNA deletions in hereditary inclusion body myopathy.
AB  - We have recently described an autosomal dominant hereditary inclusion body
      myopathy (h-IBM). Clinically it is is characterized by congenital joint
      contractures and slowly progressive, proximal muscle weakness and
      ophthalmoplegia. There is deterioration of muscle function between 30 and 50
      years of age. While young patients show minor pathological changes in muscle, the
      middle-aged and old patients show rimmed vacuoles and inclusions of filaments
      measuring 15-18 nm in diameter. Except for the absence of significant
      inflammation the histopathology is similar to that found in sporadic inclusion
      body myositis (s-IBM). In s-IBM mitochondrial alterations including cytochrome c
      oxidase (COX) -deficient muscle fibers are common. These are due to multiple
      mitochondrial DNA (mtDNA) deletions. In this study we investigated the occurrence
      of mitochondrial alterations in autosomal dominant h-IBM. Young affected
      individuals showed no mitochondrial changes but three patients aged 38, 51 and 59
      years, respectively, showed ragged red fibers and COX-deficient muscle fibers.
      Polymerase chain reaction analysis showed multiple mtDNA deletions. By in situ
      hybridization clonal expansions of mtDNA with deletions were demonstrated in COX
      deficient muscle fibers. Most of the analyzed deletion breakpoints showed
      nucleotide repeats flanking the deletions. The results show that COX-deficient
      muscle fibers and somatic mtDNA deletions are present in this family with h-IBM.
      The same factors may be involved in the development of mtDNA deletions in s-IBM
      and this family with h-IBM.

PMID- 10912917
TI  - The extent of neurofibrillary pathology in perforant pathway neurons is the key
      determinant of dementia in the very old.
AB  - Neurofibrillary pathology as found in Alzheimer's disease (AD) is also found in
      the normal elderly, suggesting that these changes may be part of the aging
      process. In this study, we assessed the densities and distribution of structures
      recognized by the monoclonal antibody (mAb) to phosphorylated tau (AT8) in the
      hippocampal formation and medial temporal isocortex of 19 centenarians. Of these,
      4 cases were demented and 15 non-demented. AT8 immunoreactivity correlated with
      the global deterioration scale (GDS). The density of both intraneuronal
      neurofibrillary tangles (I-NFTs) and neuritic clusters (NCs) significantly
      correlated with the GDS in the layer II of the entorhinal cortex (r = 0.66, P =
      0.005 and r= 0.611, P = 0.01, respectively). Density of I-NFTs in the subiculum
      (r = 0.491; P = 0.034) also correlated significantly. No other area was found to
      be statistically significant. Importantly, no correlation was found when demented
      and non-demented centenarian cases were analyzed separately, suggesting that the
      difference marks a fundamental shift between AD and non-demented individuals.
      This assertion is supported by the significantly higher densities of I-NFTs and
      NCs in the transentorhinal (P = 0.043 and P = 0.011, respectively) and layer II
      of the entorhinal cortex (P = 0.02 and P = 0.007, respectively), and I-NFTs in
      the subiculum (P < 0.001) and CAI (P = 0.011) in the demented group when compared
      with the non-demented cases. Granular diffuse deposits, an early stage parameter
      of the neurofibrillary pathology involving accumulation of non-fibrillar
      abnormally phosphorylated tau protein did not correlate with the GDS or between
      the two groups studied. This study, combining morphometric and confocal analyses,
      not only provides further evidence that, in the brains of patients with AD, the
      perforant pathway is highly sensitive to tau pathology but also that involvement
      is distinct from the changes of normal aging, even of the oldest old.

PMID- 10912919
TI  - Ubiquitin-immunoreactive skein-like inclusions in the neostriatum are not
      restricted to amyotrophic lateral sclerosis, but are rather aging-related
      structures.
AB  - We examined the presence of ubiquitin-immunoreactive skein-like inclusions (SLI)
      in the neostriatum and spinal cord in normal individuals and patients with
      different neurodegenerative diseases. Ubiquitin-immunoreactive SLI in the
      neostriatum were observed both in the normal individuals and in the patients with
      a variety of neurodegenerative diseases. In particular, SLI were frequently seen
      in normal aged subjects and certain neurodegenerative diseases, such as
      progressive supranuclear palsy and myotonic dystrophy. In contrast, the
      occurrence rate of SLI in cases with Pick's disease and multiple system atrophy
      tended to decrease. On the other hand, SLI in the spinal anterior horn were
      detected in cases of amyotrophic lateral sclerosis, but not in any cases with
      other neurodegenerative diseases. SLI in the neostriatum were also identifiable
      using phosphotungstic acid-hematoxylin and Gomori trichrome staining. Ubiquitin
      immunoelectron microscopy demonstrated that the SLI in the neostriatum
      corresponded to bundles of filaments. These features of SLI in the neostriatum
      were quite similar to those of intracytoplasmic rod-like inclusions (RLI) in the
      large neurons of caudate nucleus, which were first described by Kojima and Ogawa
      in 1974. Our findings indicate that SLI in the neostriatum are ubiquitin-related
      structures whose occurrence increases by aging, and less frequently accompany
      several neurodegenerative diseases, and are identical to at least some RLI.

PMID- 10912918
TI  - Apolipoprotein E4 promotes the early deposition of Abeta42 and then Abeta40 in
      the elderly.
AB  - The apolipoprotein Eepsilon4 allele (ApoEepsilon4) is associated with a selective
      increase in deposition of the 40-amino acid form of the beta-amyloid peptide
      (Abeta40) in endstage Alzheimer's disease. To determine how apoE genotype affects
      the early events in beta-amyloid pathogenesis, we analyzed the medial temporal
      lobes of 244 elderly persons who were not clinically demented using antibodies
      selective for the C termini of Abeta40 and Abeta42. We found that: (1) the number
      of both Abeta42- and Abeta40-positive senile plaques increase with age; (2)
      Abeta42 appears at younger ages, and in more amyloid deposits, than does Abeta40
      in all ApoE groups; (3) when compared at similar ages, older persons with
      ApoEepsilon4 are more likely to have Abeta42- and Abeta40-immunoreactive deposits
      than are persons without ApoEepsilon4; (4) Abeta40-containing plaques arise at
      least a decade later than do Abeta42 plaques, and are seldom found in the medial
      temporal lobe of older persons lacking ApoEepsilon4; and (5) in the absence of
      overt Alzheimer's disease, cerebral amyloid angiopathy is rare in the elderly,
      but in our sample was significantly augmented in ApoEepsilon4 homozygotes. We
      conclude that ApoEepsilon4 hastens the onset of Abeta42 deposition in the
      senescent brain, which in turn fosters the earlier evolution of fibrillar,
      Abeta40-positive plaques, thereby increasing the risk of Alzheimer's disease.

PMID- 10912920
TI  - Alaskan Husky encephalopathy--a canine neurodegenerative disorder resembling
      subacute necrotizing encephalomyelopathy (Leigh syndrome).
AB  - The gross and histopathological findings in the brain and spinal cord of five
      Alaskan Husky dogs with a novel incapacitating and ultimately fatal familial and
      presumed hereditary neurodegenerative disorder are described. Four dogs presented
      with neurological deficits before the age of 1 year (7-11 months) and one animal
      at 2.5 years old. Clinical signs in all dogs were of acute onset and included
      ataxia, seizures, behavioral abnormalities, blindness, facial hypalgesia and
      difficulties in prehension of food. In animals allowed to survive, the disease
      was static but with frequent recurrences. Pathological findings were limited to
      the central nervous system. Grossly visible bilateral and symmetrical cavitated
      foci were consistently present in the thalamus with variable extension into the
      caudal brain stem. Microscopic lesions were more widespread and included foci of
      bilateral and symmetrical degeneration in the basal nuclei, midbrain, pons and
      medulla, as well as multifocal lesions at the base of sulci in the cerebral
      cortex and in the gray matter of cerebellar folia in the ventral vermis. Neuronal
      loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and
      hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration
      were the main histopathological findings. In addition, a population of reactive
      gemistocytic astrocytes with prominent cytoplasmic vacuolation was noted in the
      thalamus. Lesions of this nature in this distribution within the neuroaxis have
      not been reported in dogs. The neuropathological findings resemble Leigh's
      disease/subacute necrotizing encephalomyelopathy of man. Neuronal sparing in
      conjunction with apparently transient astrocytic vacuolation point to the
      possible pathogenetic role of astrocytes in the evolution of these lesions. An
      inherited metabolic derangement of unknown nature is postulated as the cause of
      this breed-specific disorder.

PMID- 10912921
TI  - Chronic inflammatory demyelinating polyneuropathy associated with
      dysglobulinemia: a peripheral nerve biopsy study in 18 cases.
AB  - The possible occurrence of chronic inflammatory demyelinating polyneuropathy
      (CIDP) in association with an identified dysglobulinemic status is recognized and
      a causal relationship between the two has been suggested. We had the opportunity
      to study 18 patients presenting with CIDP and dysglobulinemia. This was an IgG
      monoclonal gammopathy (IgG MG) in 8 cases, an IgM monoclonal gammopathy (IgM MG)
      in 8, an IgG-IgM biclonal gammopathy in 1 case and an IgM monoclonal
      cryoglobulinemia in another. A peripheral nerve biopsy specimen was available for
      all patients and the morphological findings in these specimens in the cases of
      CIDP with IgG MG or cryoglobulin did not differ from those without, whereas
      characteristic features were observed in the cases of CIDP with IgM MG and anti
      myelin associated glycoprotein activity.

PMID- 10912922
TI  - Association of osteopontin with ischemic axonal death in periventricular
      leukomalacia.
AB  - Osteopontin (OPN) is a bone matrix protein expressed my macrophages and related
      to the process of tissue calcification, and is also known to protect ischemic
      cells. To understand how OPN is involved in the process of ischemic axonal death
      in periventricular leukomalacia (PVL), we examined the immunoreactivity of OPN
      and ionized calcium binding adaptor molecule 1 (Iba1; microglia/macrophage
      marker) at various stages of PVL. OPN immunoreactivity paralleled the number of
      Iba1-positive foam cells; a finding which suggests the production of OPN protein
      by foam cells. OPN immunoreactivity was not found in either normal white matter
      or acute PVL lesions, but was detected at the subacute and chronic stages in
      swollen and calcified axons bordering the ischemic zone. These findings suggest
      that OPN is closely associated with death of swollen axons at the periphery of
      the ischemic zone, regulating the presence or absence of calcification.

PMID- 10912923
TI  - Changes of Fas and Fas ligand immunoreactivity after compression trauma to rat
      spinal cord.
AB  - This immunohistochemical study evaluated Fas and Fas ligand (FasL) in the rat
      nervous system and their changes in the spinal cord subjected to compression.
      Normal spinal cord showed a low level of Fas and FasL immunoreactivity in the
      white matter except in the corticospinal tracts. Fas and FasL immunoreactivity
      seemed to be located in axons and their myelin sheaths. Other regions of the
      nervous system did not show immunoreactivity to Fas and FasL. Moderate and severe
      compression injury of the spinal cord resulted in a reduction of Fas and FasL
      immunoreactivity in the white matter of injured T8-9 segments at 4 h and a
      complete loss at 1 day after trauma. This was seen even in the remaining white
      matter. In contrast, increased immunoreactivity to Fas and FasL was present in
      the cranial T7, caudal T10 (moderate injury) and T12 (severe injury) segments at
      day 4 with most intense staining were seen at day 9 after trauma. Increased Fas
      and FasL immunoreactivity may have pathophysiological implications for the
      development of secondary injuries after trauma to the spinal cord. Fas-FasL
      interactions may for instance be involved in apoptosis of oligodendrocytes which
      occurs as a delayed phenomenon after trauma to the spinal cord. The integrity of
      myelin sheaths may in this way be jeopardized by apoptosis of oligodendrocytes.

PMID- 10912924
TI  - Cytochrome c oxidase deficiency in the muscle of patients with zidovudine
      myopathy is segmental and affects both mitochondrial DNA- and nuclear DNA-encoded
      subunits.
AB  - Zidovudine (AZT) can induce a mitochondrial disorder associated with
      mitochondrial (mt) DNA depletion affecting skeletal muscle, heart, and liver.
      Zidovudine myopathy is characterized by ragged-red fibers and partial cytochrome
      c oxidase (COX) deficiency. We evaluated at a single fiber level the expression
      of COX II (mtDNA-encoded) and COX IV (nuclear DNA-encoded) subunits in 12 HIV
      infected patients with zidovudine myopathy. We also evaluated COX activity on
      longitudinal muscle sections in one patient. In all patients, evaluation of the
      expression of COX II and COX IV subunits showed focal deficiency. All fibers
      negative for COX II or COX IV were negative by COX histochemistry; 32-92% (median
      61%) of COX-negative fibers were negative for COX II antigens, and 7-58% (median
      28%) were negative for COX IV antigens. One hundred and thirty-nine of 317 COX
      negative fibers 139 (43.8%) were selectively negative for COX II; 28 of 317
      (8.8%) COX-negative fibers were selectively negative for COX IV. A study of
      longitudinal distribution of COX activity demonstrated that COX deficiency was
      segmental with blurred borders, as previously observed in patients with myoclonus
      epilepsy with ragged-red fibers. We conclude that proteins encoded by mtDNA are
      predominantly, but not exclusively, involved in zidovudine myopathy. Our results
      confirm the value of single muscle fiber evaluation in the assessment of
      mitochondrial abnormalities related to zidovudine.

PMID- 10912925
TI  - Coexisting pathologies in the brain: influence of vascular disease and
      Parkinson's disease on Alzheimer's pathology in the hippocampus.
AB  - The finding of more than one coexisting brain pathology in dementia sufferers is
      not unusual. However, it is unclear how these different diseases may interact or
      influence the evolution of one another. In this study we analyse the hippocampal
      expression patterns of hyperphosphorylated tau, paired helical filament (PHF)
      related protein, beta-amyloid and synaptophysin in a group of Alzheimer's disease
      (AD) sufferers with and without additional pathology. Compared to cases with only
      AD-type pathology we found that the presence of additional vascular disease
      augmented the accumulation of hyperphosphorylated tau in the CA1 region of the
      hippocampus without affecting PHF formation in cases with mild AD changes and
      reduced the extent of PHF formation in the CA2/3 and CA4 regions of the
      hippocampus in cases with severe AD pathology. We also found that synaptophysin
      immunoreactivity in the CA4 and dentate gyrus in pure AD was inversely related to
      the extent of amyloid accumulation but not to neurofibrillary pathology in the
      same regions. These relationships were lost when additional pathology was
      present. Memory scores obtained during life correlated closely with
      hyperphosphorylated tau and PHF-related protein expression in CA1 in pure AD but
      not in AD with additional pathology. Total amyloid and synaptophysin expression
      in the hippocampus did not correlate with memory scores in any patient group. Our
      findings suggest that the interactions of two pathologies in the hippocampus are
      complex and may differ depending on the stage reached in the evolution of a
      progressive disease such as AD.

PMID- 10912926
TI  - Neuron loss in cerebellar cortex of rats exposed to mercury vapor: a
      stereological study.
AB  - Mercury vapor produces tremor in humans and experimental animals. We have
      previously reported that mercury vapor intoxication over an 8-week period induces
      only subtle changes in dorsal root ganglia and nerve roots in rats. In the
      present study we have carried out stereological analyses of the cerebellum of the
      same rats, and demonstrated significant losses of Purkinje cells (12.7%, 2P =
      0.005) and granule cells (15.6%, 2P = 0.016). All sizes of Purkinje cells were
      lost with an equal probability, i.e. there were no indication of any preferential
      loss of any subpopulation of the neurons. The volume of the granular cell layer
      was significantly reduced (18.9%, 2P = 0.0 15), whereas the volumes of the
      molecular layer and the white matter were unchanged. Previous stereological
      studies have demonstrated that methyl mercury intoxication primarily induces
      degeneration in the peripheral nervous system, while sparing the cerebellum. We
      therefore suggest that metallic mercury vapor and methyl mercury have different
      toxicological profiles in rats, where metallic mercury vapor mainly affects the
      central nervous system and methyl mercury mainly affects the peripheral nervous
      system.

PMID- 10912927
TI  - Vascular endothelial growth factor (VEGF) is elevated in brain tumor cysts and
      correlates with tumor progression.
AB  - Vascular endothelial growth factor (VEGF), a key regulatory protein in
      neoangiogenesis, is strongly expressed in a variety of primary brain tumors,
      particularly malignant gliomas. In previous studies, high levels of VEGF were
      also reported in tumor cysts of glioblastomas. Using an ELISA method we measured
      the concentration of VEGF in matched samples of aspiration fluid from tumor cysts
      and serum. Samples were collected from 14 patients with primary brain tumors of
      various histology (six glioblastomas, one protoplasmatic astrocytoma, two
      pilocytic astrocytomas, one ependymoma, one meningioma, and three
      craniopharyngiomas) and two patients with solitary cystic brain metastases from
      adenocarcinomas of the lung. Aspiration fluids of tumor cysts from all patients
      revealed high VEGF levels ranging between 882 and 1,263,000 pg/ml, which were 2
      to more than 2,000 times higher than the corresponding serum levels. Maximum VEGF
      levels were detectable in cyst fluids from recurrent glioblastoma. Serum VEGF
      levels ranged between 125 and 716 pg/ml and did not differ from serum levels in
      145 healthy volunteers. In a single patient with metastatic lung cancer the
      concentration of VEGF in serum and cyst fluid was determined during disease
      progression. During 60 days of follow-up VEGF concentrations in the cyst fluid
      collected by puncture of an Ommaya reservoir increased 650-fold, while serum
      levels remained rather constant. These findings indicate that immunoreactive VEGF
      is produced at the tumor site and abundantly released into the cyst fluid of
      primary and metastatic brain tumors. Interestingly, this abundant local release
      is not reflected in serum VEGF levels, even in the case of very high VEGF
      concentrations in tumor cysts. Thus, VEGF may be biologically relevant for the
      formation of tumor cysts in brain tumors and correlates with local disease
      progression.

PMID- 10912928
TI  - Ganglion cells in the posterior pituitary: result of ectopia or
      transdifferentiation?
AB  - Histologic examination revealed large ganglion cells within the posterior
      pituitary of an 80-year-old woman who died of myocardial infarction. Apparently
      fully mature, the cells were an incidental finding scattered within hyperplastic
      foci of pars intermedia (PI)-derived cells (basophil invasion) on histologic
      examination of the pituitary obtained at autopsy. Immunocytochemistry showed
      staining reactivity for neuron-specific enolase, synaptophysin, alpha subunit of
      the glycoprotein hormones and beta-endorphin. The presence of these ganglion
      cells with features similar to those of magnocellular hypothalamic neurons could
      be considered the result of abnormal migration during the early phase of
      embryonic life, or differentiation/maturation of neuroblasts, presumed to occur
      in the embryonic neurohypophysis. Alternatively, transdifferentiation from
      proliferating PI cells may explain the emergence of neurons; a hypothesis
      supported by the proximity and shared alpha subunit, and beta-endorphin
      immunoreactivities of the two cell types.

PMID- 10912929
TI  - Increased cellularity of tumor-encased native vessels in prostate carcinoma is a
      marker for tumor progression.
AB  - Changes in the native vasculature of the prostate gland associated with prostate
      adenocarcinoma have not been well characterized. Eighty-nine whole mounts of
      entirely submitted radical prostatectomies were reviewed. Thirty prostates with a
      minimum of five native arteries surrounded by carcinoma with corresponding
      control arteries were found and included in this study. The number of nuclei in
      the media of native arteries was recorded per 0.138 mm2 using a 40x objective.
      The number of nuclei in vessels embedded in carcinoma (n = 204) was increased
      when compared with controls (26.37 versus 20.58 mean nuclei per 0.138 mm2; P <
      .001). Pathologic Stage T3 carcinomas contained vessels that were more cellular
      than stage T2 (P < .001). Vessels embedded in Gleason Grade 4 showed more
      cellularity than arteries embedded in Gleason Grade 3 (P < .002). Increased media
      cellularity of native prostate vessels encased in carcinoma is a histologic
      feature of higher grade/stage prostate carcinoma and provides positive indicator
      of advanced prostate cancer.

PMID- 10912930
TI  - Telomerase activity significantly correlates with chromosome alterations, cell
      differentiation, and proliferation in lung adenocarcinomas.
AB  - Telomerase activity was examined by the telomeric repeat amplification protocol
      assay in 25 cases of lung adenocarcinoma, in relation to cancer cell
      differentiation, proliferation, and chromosome alterations. Telomerase activity,
      chromosome alterations, and cell proliferation assessed by Ki-67 labeling were
      significantly lower (P < .001 to .05) in well-differentiated (10 cases) than in
      moderately differentiated (8 cases) or poorly differentiated (7 cases) lesions.
      Telomerase activity by semiquantitative analysis with scoring of 0 to 3 was
      significantly correlated with similarly graded chromosome alterations (P < .05)
      and Ki-67 labeling indices (P < .002). Telomerase activity and chromosome
      alteration (T-C) indices generated by multiplication of telomerase activity and
      chromosome alteration scores also showed a significant correlation with cell
      differentiation. The Clara cell subtype, confirmed by electron microscopic
      analysis, significantly predominated in the well-differentiated group, showing a
      low grade of telomerase activity and chromosome alterations and low Ki-67
      labeling indices, suggesting clinical relevance. No significant association of
      telomerase activity was found with p53 protein accumulation or Bcl-2 protein
      expression. The good correlation of telomerase activity with chromosome
      alterations, cell differentiation, and Ki-67 labeling indices suggests that this
      parameter might have potential application in estimation of prognosis.

PMID- 10912931
TI  - Histologic grading of breast cancer: linkage of patient outcome with level of
      pathologist agreement.
AB  - In the histologic grading of invasive breast cancer with the Nottingham
      modification of the Scarff-Bloom-Richardson grading scheme (NSBR), it has been
      found that when pathologists disagree, they tend not to disagree by much.
      However, if tumor grade is to be used as an important parameter in making
      treatment decisions, then even this generally small degree of pathologist
      variability in assessing grade needs to be correlated with patient outcome.
      Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for
      patient outcome data. Kaplan-Meier survival curves were constructed for NSBR
      scores grouped according to the level at which pathologists tend to agree in
      assessing grade, from a reproducibility perspective. For example, if a given
      tumor were assessed by several pathologists as having either an NSBR score of 5
      or 6, then what is the correct score--the intermediate-grade Score 6 assessments
      or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data
      such that data from patients with Score 5 tumors are grouped with patients having
      Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed
      with each other (that the tumor was either score 5 or 6) is better matched with
      patient outcome. In response to the above example, it was not surprising to find
      that patients with Score 5-6 tumors had a probability of survival between the
      established low and intermediate NSBR final combined grades. However, it is the
      discussion of this approach that highlights that optimal use of grading requires
      awareness of the level of pathologist agreement and understanding the value of
      pathologists' reaching consensus in assessments. Also, knowledge of possible
      clinical decision thresholds can help in providing relevant interpretations of
      grading results.

PMID- 10912932
TI  - Immunohistochemical study of type-1 blood antigen expressions in thyroid tumors:
      the significance for papillary carcinomas.
AB  - Immunohistochemical expressions of type 1 blood group antigens were studied for
      95 cases of thyroid tumors, including 29 follicular adenomas, 23 follicular
      carcinomas, and 43 papillary carcinomas, applying monoclonal antibodies against
      DU-PAN-2, CA19-9, Lewis(a) (Le(a)), and Lewis(b) (Le(b)). Normal thyroid tissue
      invariably failed to express all four antigens. In follicular adenomas, DU-PAN-2
      and CA19-9 were focally expressed in 7% and 21% of cases, and in follicular
      carcinomas, CA19-9 expression was limited to one case (4%); all cases were
      negative for DU-PAN-2. No or little expression of Le(a) or Le(b) was observed in
      these follicular tumors. In contrast, DU-PAN-2, CA19-9, Le(a), and Le(b) were
      expressed in 98%, 84%, 33%, and 49% of 43 papillary carcinomas, respectively. The
      positive stainings were observed mainly on the luminal surface of the tumor
      cells. The number of tumor cells that expressed DU-PAN-2 generally was greater
      than that of tumor cells that expressed CA19-9, Le(a), or Le(b). There was no
      significant difference in antigen expressions in female papillary carcinomas
      between subjects who were younger and older than 50 years old. The results
      suggest that DU-PAN-2 would be a useful immunohistochemical marker for
      distinguishing papillary carcinomas from follicular tumors. These
      immunohistochemical profiles imply the following: the activity of alpha2-3
      sialyltransferase, a specific glycosyltransferase, would be more strongly
      enhanced in papillary carcinomas than in follicular tumors; the antigen
      expressions in papillary carcinomas may not be related to the alteration of the
      female sex hormone environment.

PMID- 10912933
TI  - Squamous cell carcinoma of the thyroid: an aggressive tumor associated with tall
      cell variant of papillary thyroid carcinoma.
AB  - Squamous cell carcinoma of the thyroid (SCT) is an unusual neoplasm thought to
      arise as a primary tumor or as a component of an undifferentiated carcinoma. The
      role of p53 and Ki-67 as prognostic indicators in this type of tumor is not
      known. We studied eight cases of primary SCT. Three cases were analyzed for Ki-67
      by immunohistochemistry and for p53 by immunohistochemistry and loss of
      heterozygosity. Seven patients were women, and one was a man (age range, 31 to 90
      years). SCT were firm, were tan with areas of necrosis, and ranged in size from 2
      to 8 cm. Histologically, they had islands of squamous cells with spindle cell
      areas (two of eight). In four of eight cases, SCT was associated with the tall
      cell variant of papillary carcinoma (TCV). Positive staining for p53 was seen in
      two of three cases, and in one of three the TCV was also positive for p53. Mean
      MIB1 labeling index was 30% and 17% in SCT and TCV, respectively. At the time of
      presentation, six of eight patients had cervical lymph node metastases. In one
      case, the primary tumor had SCT and TCV; however, only the SCT component
      metastasized. After mean follow-up of 48 months, one patient had died of disease,
      five were alive with recurrent or metastatic tumor, and two were lost to follow
      up. Primary SCT is an aggressive neoplasm that may be found in association with
      TCV. p53 expression and high MIB1 labeling index occur in these tumors and may be
      useful prognosticators.

PMID- 10912934
TI  - Pulmonary pathology of Erdheim-Chester disease.
AB  - Erdheim-Chester disease (ECD) is a rare non-Langerhans' cell histiocytosis that
      may present with pulmonary symptoms. The condition seems to be nonfamilial and
      typically affects middle-aged adults. Radiographic and pathologic changes in the
      long bones are diagnostic, but patients often present with extraskeletal
      manifestations. Advanced pulmonary lesions are associated with extensive fibrosis
      that may lead to cardiorespiratory failure. The clinical, radiologic, and
      pathologic features of six patients with ECD with lung involvement are presented.
      The patients were three men and three women (mean age, 57). Five presented with
      progressive dyspnea, and one presented with diabetes insipidus. Open-lung
      biopsies showed histiocytic infiltrates in a lymphangitic pattern with associated
      fibrosis and lymphoplasmacytic inflammatory infiltrates. The histiocytes did not
      stain with periodic acid-Schiff. Immunoperoxidase studies performed on specimens
      from five of six patients showed that the histiocytes were positive for CD68 and
      Factor XIIIa and negative for CD1a. Specimens from two patients exhibited
      immunoreactivity for S-100 protein. Electron microscopy studies performed on
      specimens from two patients showed phagocytic lysosomes but no Birbeck granules.
      Clinical follow-up of up to 16 years was available. At the end of that time, five
      patients were dead of complications related to their disease; one patient remains
      alive 4 years after diagnosis but with severe respiratory compromise. ECD is a
      rare non-Langerhans' cell histiocytosis that may present as interstitial lung
      disease and resemble other pulmonary conditions, particularly usual interstitial
      pneumonitis and pulmonary Langerhans' cell histiocytosis. Recognition of this
      entity will allow better assessment of its true incidence, therapeutic options,
      and prognosis.

PMID- 10912935
TI  - Prognostic significance of apoptosis in synovial sarcoma: correlation with
      clinicopathologic parameters, cell proliferative activity, and expression of
      apoptosis-related proteins.
AB  - bcl-2 overexpression in synovial sarcomas has been recently reported. Although it
      is widely known that bcl-2 suppresses apoptosis in various cells, there are no
      studies that have examined the significance of apoptosis in synovial sarcoma. In
      the present study, we visualized apoptotic tumor cells by the terminal
      deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick end
      labeling (TUNEL) method in 49 cases of primary synovial sarcoma. The degree of
      apoptosis was analyzed in relation to several clinicopathologic parameters, cell
      proliferative activity, and immunohistochemical expression of apoptosis-related
      proteins, including bcl-2, bax, bcl-x, bak, p53, p21 (WAF1/CIP1), Fas, and Fas
      ligand. TUNEL index (TUNEL-I) significantly correlated with the mitotic index
      (MI) (n = 0.60, P < .0001) and Ki-67 labeling index (MIB1-I) (n = 0.52, P =
      0.0005). There was a highly significant association between high TUNEL-I value
      (>.8%) and poor prognosis (log-rank test; P < .0001). Many synovial sarcomas were
      diffusely positive for bcl-2 family proteins (bcl-2, bax, bcl-x, and bak) and
      were negative or only sporadically positive for Fas, Fas ligand, p53, and p21
      (WAF1/CIP1) proteins. The results indicated that increased rate of apoptosis in
      primary synovial sarcoma was considered to be an indicator of poor prognosis. In
      addition, apoptosis in synovial sarcoma may be controlled by multiple apoptosis
      regulating mechanisms, including the bcl-2 family.

PMID- 10912936
TI  - Immunoreactivity of B-cell markers (CD79a, L26) in rare cases of extranodal
      cytotoxic peripheral T- (NK/T-) cell lymphomas.
AB  - The monoclonal antibodies L26 (CD20) and CD79a are very useful reagents for the
      immunohistochemical assessment of B-cell lineage in lymphoproliferative
      disorders. Although very few CD20-positive peripheral T-cell lymphomas (PTL) have
      been reported, comprehensive analyses of CD79a reactivity in extranodal PTL and
      NK/T-cell lymphomas have not been performed previously. This study investigated
      CD79a (clone JCB117) and CD20 reactivity in 94 extranodal non-B-cell lymphomas
      (enteropathy-type intestinal T-cell lymphoma [n = 52], nasal NK/T-cell lymphoma
      [n = 11], and primary cutaneous PTL [n = 31]) and in 17 cases of nodal PTL,
      unspecified. In four cases (enteropathy-type intestinal T-cell lymphoma [n = 3]
      and nasal NK/T-cell lymphoma [n = 1]), the majority of tumor cells stained for
      CD79a (all CD20 negative) and one cutaneous PTL, unspecified, was CD20 positive
      (CD79a negative). Extensive immunophenotyping and polymerase chain reaction-based
      molecular analyses revealed that all five B-cell marker-positive extranodal
      lymphomas had a cytotoxic phenotype and did indeed represent monoclonal
      peripheral T-cell proliferations. To minimize the risk of misinterpretation of
      lymphoma cell lineage, especially in cases of extranodal, lymphoproliferative
      disease, we suggest the use of both CD79a and CD20 in combination with a panel of
      antibodies reactive to T cells, such as betaF1 and CD5, and to T cells and NK
      cells, such as CD3, CD2, CD56, and TIA-1.

PMID- 10912937
TI  - Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver:
      MOC31 compares favorably with other putative markers.
AB  - Distinguishing hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA)
      and cholangiocarcinoma (CC) can, at times, be difficult and sometimes requires
      immunohistochemical analysis. Recently, MOC31, an antibody directed against a
      cell surface glycoprotein, has been shown to be useful in separating HCC from
      both MA and CC; however, no study has compared MOC31 and other frequently used
      immunostains. We compare MOC31 with other commonly used immunostains for HCC, MA,
      and CC. Formalin-fixed, paraffin-embedded tissue sections from 57 previously
      characterized hepatic neoplasms (13 HCC, 14 CC, 3 combined HCC-CC, and 27 MA)
      were immunostained with antibodies directed against MOC31, cytokeratin (CK) 7,
      CK20, alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen, Ber-EP4, and
      Factor XIII-A. Two pathologists reviewed slides, and positivity was defined as
      more than 1% of cells staining with the appropriate pattern. Positive MOC31
      immunostaining was seen in 0 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 27 of 27
      MA; the staining was strong and diffuse. CK20 reactivity was observed in 0 of 13
      HCC, 2 of 14 CC, 0 of 3 HCC-CC, and 12 of 27 MA; CK7 immunostained 4 of 13 HCC,
      13 of 14 CC, 3 of 3 HCC-CC, and 15 of 27 MA; AFP was detected in 4 of 13 HCC and
      2 of 3 HCC-CC, whereas all CC and MA were negative; polyclonal carcinoembryonic
      antigen showed immunoreactivity in 12 of 13 HCC and 3 of 3 HCC-CC in a
      canalicular pattern, whereas diffuse positivity was identified in 13 of 14 CC and
      26 of 27 MA; Ber-EP4 immunostained 1 of 13 HCC, 14 of 14 CC, 2 of 3 HCC-CC, and
      26 of 27 MA; and Factor XIII-A was negative in all HCC, CC, and MA. MOC31
      expression distinguished HCC from adenocarcinoma in 56 of 57 cases. AFP was
      specific for HCC but was not sensitive. CK7 and CK20 have limited utility in
      distinguishing HCC from CC or MA, and Factor XIII-A is not useful. Ber-EP4
      staining was similar to MOC31, but one HCC did stain with Ber-EP4. Polyclonal CEA
      yields similar numerical results as MOC31, but the focal nature of the staining
      and occasional difficulty in evaluating the pattern can make interpretation
      problematic. We conclude that MOC31 should be a component of the
      immunohistochemical panel to distinguish HCC from CC and MA.

PMID- 10912938
TI  - Myocardial extramedullary hematopoiesis: a clinicopathologic study.
AB  - Extramedullary hematopoiesis (EMH) after fetal development is uncommon and is
      most often seen in patients who have hematologic disorders. EMH unassociated with
      hematologic disease is rare. After the recent observation of EMH in a myocardial
      infarct, we sought to determine the frequency and clinicopathologic setting of
      EMH in myocardial tissues submitted for pathologic examination. Hematoxylin and
      eosin (H&E)-stained sections from 805 consecutive myocardial samples (207
      surgical specimens, 598 autopsy specimens) were examined retrospectively. The
      presence of immature erythroid or myeloid cell clusters in intramyocardial
      capillaries or stroma was considered sufficient for the diagnosis of EMH.
      Immunoperoxidase studies confirming the nature of the hematopoietic cell
      infiltrate were performed in selected cases. Foci of EMH (often multiple) were
      identified in 15 of 207 surgical hearts (7.2%) and in 22 of 598 autopsy hearts
      (3.7%). Patient ages (exclusive of premature infants) ranged from 2 weeks to 73
      years (median, 13 years). Twenty-four of 37 (65%) EMH-positive cases were
      associated with infarcts in various stages of repair (accounting for 11 of 68
      [16.2%] of all infarcts in surgical specimens and 13 of 86 [15.1%] of infarcts in
      autopsy specimens). Acute infarcts less than 72 hours old, excluding those with
      acute extension, were not associated with EMH. Viral myocarditis and myocardial
      hypertrophy with fibrosis accounted for primary diagnoses in the nonischemic, EMH
      positive surgical cases, whereas seven of nine nonischemic, EMH-positive autopsy
      cases involved premature or term infants with no obvious myocardial disease.
      Another autopsy patient had sarcoidosis with myelophthisic involvement of her
      bone marrow and represented one of only two cases overall in which a
      hematopoietic disorder was coexistent or suspected. Myocardial EMH is relatively
      common after myocardial infarct but is rarely encountered in normal or
      nonischemic myocardium. Its presence in healing but not early acute stages of
      infarct suggests that EMH results from inflammation- or repair-associated trophic
      factors, not from ischemia itself.

PMID- 10912940
TI  - Hyperplastic-like mucosal change in Crohn's disease: an unusual form of
      dysplasia?
AB  - Patients with Crohn's disease are at increased risk of developing intestinal
      adenocarcinoma. Dysplasia is both a marker and a precursor of adenocarcinoma in
      this setting. In a review of our cases of Crohn's-related adenocarcinoma, we
      noted a peculiar hyperplastic-like mucosal change (HPC) in mucosa both adjacent
      to and distant from the adenocarcinoma in some cases. However, the significance
      of this change is unknown. We evaluated 30 cases of Crohn's-related
      adenocarcinoma and 30 age- and site-matched resection specimens with Crohn's
      disease without adenocarcinoma to determine the prevalence of this mucosal
      alteration in these groups. HPC was recognized by a diffuse expanse of flat
      mucosa with an architecture resembling that seen in colorectal hyperplastic
      polyps and composed of cells with cytologically bland basal nuclei and apical
      cytoplasmic mucin distention. The relationship of the HPC to the adenocarcinoma
      was noted in the Crohn's-related adenocarcinoma cases. An immunohistochemical
      stain for p53 (antibody DO7) was performed on all cases with HPC in both groups.
      HPC was identified in 10 of 30 (33%) cases of Crohn's-related adenocarcinoma
      compared with 3 of 30 (10%) cases in the control group (P = .03). In the 10 cases
      of Crohn's-related adenocarcinoma with HPC, this alteration was found adjacent to
      the adenocarcinoma in 3 cases, distant to the adenocarcinoma in 5 cases, and both
      adjacent to and distal from the adenocarcinoma in 2 cases. In two specimens, HPC
      was seen immediately adjacent to adenocarcinoma in the absence of adjacent
      dysplasia. p53 immunoreactivity was noted in HPC in 5 of 10 (50%) Crohn's-related
      adenocarcinomas. In contrast, p53 immunoreactivity was not seen in HPC in the
      three control cases with this mucosal alteration. In conclusion, HPC is found
      significantly more commonly in mucosa both adjacent to and distant from Crohn's
      related adenocarcinoma when compared with age- and site-matched controls. In
      addition, p53 immunoreactivity is more commonly seen in HPC in cases of Crohn's
      related adenocarcinoma compared with controls. These data suggest that this
      mucosal alteration may, in some cases, represent an unusual form of dysplasia in
      this setting.

PMID- 10912939
TI  - Image analysis and flow cytometric DNA studies of benign and malignant body
      cavity fluids: reappraisal of the role of current methods in the differential
      diagnosis of reactive versus malignant conditions.
AB  - Cytologic examination of body fluids is commonly performed in the clinical
      laboratory. Determination of the presence of malignancy may sometimes be
      difficult. In this study, we prospectively studied 60 body fluids with a panel of
      antibodies, including MOC-31, epithelial membrane antigen, carcinoembryonic
      antigen, B72.3, keratin, desmin, and CA-125. DNA and S-phase studies were
      performed both by flow cytometry and image analysis. Thirty-seven fluids were
      classified as benign and 23 were classified as malignant. The sensitivity of the
      antibodies for identification of carcinoma in descending order of percentage
      detection rate were MOC-31 (95%), epithelial membrane antigen (93%), B72.3 (84%),
      and carcinoembryonic antigen (80%). Desmin stained mesothelial cells in all
      cases. CA-125 gave similar results but was less specific. Flow cytometry detected
      14 of 20 malignant fluids and image analysis 17 of 23 by identifying an aneuploid
      population. Benign reactive mesothelial cells were not aneuploid. Tetraploidy due
      to reactive mesothelial cells was found in 9 of 37 body fluids. Their S-phase
      fraction was low (average, 3.2%). Tetraploidy in malignant cells was
      distinguished from the reactive mesothelial cells by high S-phase (average,
      25.95). S-phase had some use as a discriminating factor, because no benign
      reactive cases had more than 17%. However, 7 of 23 malignant cases had a value
      below 17%. DNA analysis by image was more sensitive and specific than flow.
      Either may be used when immunocytochemistry is nondiagnostic or cannot be
      performed.

PMID- 10912941
TI  - Primary mucoepidermoid carcinoma and sclerosing mucoepidermoid carcinoma with
      eosinophilia of the thyroid gland: a report of nine cases.
AB  - Mucoepidermoid carcinoma is a rare primary thyroid tumor with indolent biologic
      potential. Two types of tumors have been described under this category:
      mucoepidermoid carcinoma (MEC) and sclerosing mucoepidermoid carcinoma with
      eosinophilia (SMECE). The MEC shows both squamous and glandular differentiation
      in a background of a noninflamed gland, whereas SMECE is characterized by
      extensive sclerosis, squamous and glandular differentiation, a concomitant
      inflammatory infiltrate rich in eosinophils, and a background of lymphocytic
      thyroiditis. We present nine cases of these entities: five MEC and four SMECE.
      All tumors occurred in women (age 27 to 73 years). Five tumors showed
      extrathyroidal invasion and multiple lymph node metastases. One case of MEC
      showed a concomitant tall cell variant of papillary carcinoma with vascular
      invasion, and two cases showed intimately associated areas of usual papillary
      carcinoma. One of the latter cases also showed areas of transformation to
      anaplastic carcinoma. In all cases of SMECE and in only one case of MEC, the
      uninvolved thyroid tissue showed lymphocytic thyroiditis. Follow-up information
      was available in four of the nine cases (3 months to 7 years). Two patients with
      SMECE are alive with no evidence of disease. One patient with MEC and tall cell
      variant of papillary carcinoma died of disease after 3 months, and the patient
      with anaplastic carcinoma died after 5 months with lung metastasis. Both MEC and
      SMECE were positive for cytokeratin and negative for calcitonin. All cases of MEC
      were positive for thyroglobulin, whereas all cases of SMECE were negative. The
      immunohistochemical findings suggest that both MEC and SMECE have different
      histogenesis.

PMID- 10912942
TI  - Prognostic implications of calbindin-D28k expression in lung cancer: analysis of
      452 cases.
AB  - Calbindin D28k (Ca-D28k) acts as a buffering system to maintain cellular calcium
      homeostasis and is thought to play a role in inhibiting apoptosis. The goals of
      this study were to assess CA-D28k expression in lung carcinomas and to correlate
      these results with patient survival. A total of 452 lung carcinomas were
      immunostained with a monoclonal antibody specific for Ca-D28K using an avidin
      biotin peroxidase technique. The number of cells with nuclear staining was graded
      semiquantitatively into one of five groups: 0, fewer than 10%, 10 to 25%, more
      than 25 to 50%, more than 50 to 75%, and more than 75%. Results were correlated
      with patient survival using Kaplan-Meier survival curves. A total of 335 of 452
      (74%) lung carcinomas were positive for Ca-D28k. There was no statistically
      significant difference in the prevalence of Ca-D28k expression in tumors of
      different histologic type. Kaplan-Meier survival analysis revealed that for
      patients with adenocarcinoma, those with Ca-D28k-positive tumors had a better
      overall survival than patients with Ca-D28k-negative tumors (P = .036). This
      difference was also significant for patients with Stages I and II adenocarcinomas
      (P = .033). No statistically significant difference in prognosis was observed for
      patients with Stages III and IV adenocarcinomas or for patients with other lung
      carcinoma types of varying stage. Ca-D28k is commonly expressed in lung
      carcinomas of all histologic types. For patients with localized adenocarcinoma of
      the lung, Ca-D28k expression correlated with improved survival. No correlation
      between Ca-D28k expression and patient survival was found for disseminated
      adenocarcinoma and for other histologic types of lung carcinoma.

PMID- 10912943
TI  - Molecular genetic changes in metastatic primary Barrett's adenocarcinoma and
      related lymph node metastases: comparison with nonmetastatic Barrett's
      adenocarcinoma.
AB  - Lymph node metastasis is one of the strongest negative prognostic factors for
      patients with Barrett's adenocarcinoma (BCA). However, despite the importance of
      the metastatic process in BCA, the molecular basis of it remains poorly
      understood. To search for cytogenetic events associated with metastasis in
      regional or distant lymph nodes in BCA, we investigated 8 primary BCA and their
      lymph node metastases and compared them with 18 nonmetastatic BCA. In metastatic
      primary BCA, we observed significantly more DNA gains on 3q (P = .013), 17q (P =
      .019), and 22q (P = .021) compared with nonmetastatic primary BCA. No
      statistically significant correlation could be observed between DNA copy number
      changes and the histopathologic stage, grade, or survival (P > .05). The most
      frequent alteration observed only in lymph node metastases but not in the related
      primary tumor was loss of 2q (5 of 8). Coamplification of 7p and chromosome 17
      was found in 6 of 8 lymph node metastases. A comparison of DNA copy number
      changes between primary tumors and their corresponding metastases indicated a
      high degree of genetic heterogeneity. Fluorescence in situ hybridization analysis
      demonstrated the involvement of the Her-2/neu gene in primary BCA and its related
      lymph node metastases. Each of the investigated primary tumors and related lymph
      node metastases also showed striking heterogeneity with respect to Her-2/neu,
      with several areas displaying different levels of amplification. In summary, our
      data indicate that DNA copy number changes on 2q, 3q, 7p, 17q, and 22q may be
      involved in the metastatic process in BCA. Furthermore, the striking genetic
      heterogeneity that we found between primary BCA and its lymph node metastases may
      underlie BCA's poor responsiveness to therapy and could help explain why
      prognostic biomarkers measured exclusively in primary tumors give an incomplete
      view of the biologic potential of BCA.

PMID- 10912944
TI  - Blastic mantle cell leukemia: an unusual presentation of blastic mantle cell
      lymphoma.
AB  - Six patients had blood and bone marrow manifestations characterized by the
      presence of morphologically immature or blastic B-lineage lymphoid cells
      expressing CD5 antigen. The median patient age was 70 years, and the male-to
      female ratio was 5:1. The presence or degree of lymphadenopathy and splenomegaly
      was variable among this group at staging evaluation, although two patients did
      not have these features. One patient had an antecedent diagnosis of classical
      nodal mantle cell lymphoma, without prior morphologic blood or bone marrow
      involvement. Other patients lacked a history of underlying lymphoproliferative
      disorders. The median white blood cell count was 120 x 10(9)/L. Most patients had
      thrombocytopenia, whereas only one patient had neutropenia at presentation.
      Leukemic peripheral blood cells in these six cases were small to medium in size
      with fine or granular nuclear chromatin and small or inconspicuous nucleoli. The
      pattern of marrow involvement was interstitial or diffuse, with cells showing
      immature nuclear features resembling acute leukemia or blastic lymphoma. All
      tumors demonstrated a consistent immunophenotype of B-cell lineage, surface
      immunoglobulin positivity, and CD5 antigen expression. The progenitor cell
      associated markers CD34 and TdT were not expressed, and CD23 antigen was either
      negative (three of four cases) or only weakly present (one of four cases). The
      presence of a karyotypic t(11;14)(q13;q32) was documented in one tumor, whereas
      two other cases had BCL-1 gene rearrangements by either polymerase chain reaction
      or Southern blot analysis. Cyclin D1 mRNA overexpression was noted in three of
      four cases tested. This patient group was characterized by very poor overall
      survival (median, 3 months; range, 0.5 to 6 months). The aggregate clinical,
      pathologic, and genetic data in these unusual cases are consistent with de novo
      or predominant leukemic presentations of blastic mantle cell lymphoma. Accurate
      diagnosis in such cases is greatly facilitated by cytogenetic studies or the
      demonstration of BCL-1/cyclin D1 abnormalities.

PMID- 10912945
TI  - Correspondence re: Varma M, Linden MD, Amin MB. Effect of formalin fixation and
      epitope retrieval techniques on antibody 34betaE12 immunostaining of prostatic
      tissues. Mod Pathol 1999;12:472-8.

PMID- 10912946
TI  - Correspondence re: Kawano N, Inayama Y, Nagashima Y, Miyagi Y, Uemura H, Saitoh
      K, et al. Desmoplastic small round-cell tumor of the paratesticular region:
      report of an adult case with demonstration of EWS and WT1 gene fusion using
      paraffin-embedded tissue. Mod Pathol 1999;12:729-34.

PMID- 10912947
TI  - Determination of camptothecin analogs in biological matrices by high-performance
      liquid chromatography.
AB  - Several analogs of the topoisomerase I inhibitor camptothecin (CPT) have been
      introduced in clinical practice in the last decade. All CPT analogs are sensitive
      to a pH-dependent reversible conversion between a pharmacologically active
      lactone form and its inactive, lactone ring-opened, carboxylate form. The
      reversible conversion is also dependent on the, sometimes species-dependent,
      protein binding properties of the two forms, resulting in different lactone to
      carboxylate plasma ratios for the various analogs. Pharmacokinetic analysis of
      the CPT analogs is helpful in understanding the pharmacodynamic outcome of drug
      treatment, in clinical as well preclinical studies. Measurement of these analogs
      is habitually complicated by the chemical instability of the lactone moiety and
      necessitates a rapid centrifugation of the blood sample, preferably at the
      bedside of the patient, to collect the plasma supernatant. Since the lactone
      forms of these drugs are able to diffuse across cell membranes, including those
      of the red blood cells, rapid collection and processing is even necessary in the
      case where only the total concentrations of the CPT analogs are to be measured.
      Sample pretreatment procedures of the CPT analogs topotecan, irinotecan, 9
      aminocamptothecin and lurtotecan are summarized and discussed in this review.

PMID- 10912948
TI  - Phase II trial of gemcitabine in patients with pretreated advanced soft tissue
      sarcomas.
AB  - Because of the low number of active cytotoxic drugs and their limited activity,
      the evaluation of new anti-cancer agents for their activity in soft tissue
      sarcomas is a continuing need. The objectives of this prospective phase II trial
      of gemcitabine were to estimate the response rate and to define the toxicities of
      prolonged infusions of low-dose gemcitabine in patients with pretreated advanced
      soft tissue sarcomas. Patients were eligible if they had a histologic diagnosis
      of unresectable, recurrent or metastatic, progressive soft tissue sarcoma, and if
      they had been treated with at least one prior chemotherapy consisting of an
      anthracycline- and/or ifosfamide-containing regimen. Gemcitabine was administered
      as a 360 min infusion on days 1, 8 and 15 of a 28 day cycle. The initial dose of
      gemcitabine was 200 mg/m2 in all patients. Dose escalation to 250 mg/m2 was
      allowed in the case of stable disease and good tolerability of the drug. All 18
      patients (median age 58 years) who enrolled were treated with gemcitabine, and
      all were assessable for toxicity, response and survival. Only two of these 18
      patients had an objective response to a previous palliative chemotherapy. A
      median of 3 cycles (range 1-7) of gemcitabicin were administered. Two (11%) of
      the patients had a partial response lasting 5 and 6 months, respectively. Both of
      these patients had only lung metastases. Whereas one of these patients had a
      transient partial response to the foregoing chemotherapy (consisting of
      ifosfamide and doxorubicin), the other patient has been progressive on these
      drugs. One additional patient, progressive on ifosfamide and doxorubicin, had an
      objective response of greater than 50% confined to the lungs and stable local
      recurrence for 6 months. Six patients had stable disease for 3-6 months and nine
      patients had disease progression. The median survival was 8 months. Treatment
      generally was well tolerated with six patients having transient grade 3 non
      hematologic toxicity, four having grade 3 neutropenia, and one having grade 4
      neutropenia and thrombocytopenia. Gemcitabine, given as a prolonged infusion at a
      low dose level, has a favorable toxicity profile and displays antitumor activity
      in patients with intensively pretreated, advanced soft tissue sarcomas.

PMID- 10912949
TI  - Inter-relationships of paclitaxel disposition, infusion duration and cremophor EL
      kinetics in cancer patients.
AB  - Cremophor EL (CrEL) is a castor oil surfactant used as a vehicle for formulation
      of a variety of poorly water-soluble agents, including paclitaxel. Recently, we
      found that CrEL can influence the in vitro blood distribution of paclitaxel by
      reducing the free drug fraction, thereby altering drug accumulation in
      erythrocytes. The purpose of this study was to investigate the clinical
      pharmacokinetics of CrEL, and to examine inter-relationships of paclitaxel
      disposition, infusion duration and CrEL kinetics. The CrEL plasma clearance,
      studied in 17 patients for a total of 28 courses, was time dependent and
      increased significantly with prolongation of the infusion duration from 1 to 3 to
      24 h (p<0.03). An indirect response model, applied based on use of a Hill
      function for CrEL concentration-dependent alteration of in vivo blood
      distribution of paclitaxel, was used to fit experimental data of the 3 h infusion
      (r2=0.733; p=0.00001). Simulations for 1 and 24 h infusions using predicted
      parameters and CrEL kinetic data revealed that both short and prolonged
      administration schedules induce a low relative net change in paclitaxel blood
      distribution. Our pharmacokinetic/pharmacodynamic model demonstrates that CrEL
      causes disproportional accumulation of paclitaxel in plasma in a 3 h schedule,
      but is unlikely to affect drug pharmacokinetics in this manner with alternative
      infusion durations.

PMID- 10912950
TI  - 1,4-Anthraquinone: an anticancer drug that blocks nucleoside transport, inhibits
      macromolecule synthesis, induces DNA fragmentation, and decreases the growth and
      viability of L1210 leukemic cells in the same nanomolar range as daunorubicin in
      vitro.
AB  - 1,4-Anthraquinone (AQ) was synthesized and shown to prevent L1210 leukemic cells
      from synthesizing macromolecules and growing in vitro. In contrast, its dihydroxy
      9,10anthraquinone precursor, quinizarin, was inactive. The antitumor activity of
      AQ was compared to that of daunorubicin (DAU), which is structurally different
      from AQ but also contains a quinone moiety. AQ is equipotent to DAU against L1210
      tumor cell proliferation (IC50: 25 nM at day 2 and 9 nM at day 4) and viability
      (IC50: 100 nM at day 2 and 25 nM at day 4), suggesting that its cytostatic and
      cytotoxic activities are a combination of drug concentration and duration of drug
      exposure. Since AQ does not increase but rather decreases the mitotic index of
      L1210 cells at 24 h, it is not an antitubulin drug but might arrest early stages
      of cell cycle progression. Like DAU, a 1.5-3 h pretreatment with AQ is sufficient
      to inhibit the rates of DNA, RNA and protein syntheses (IC50: 2 microM)
      determined over 30-60 min periods of pulse-labeling in L1210 cells in vitro. In
      contrast to DAU, which is inactive, a 15 min pretreatment with AQ has the
      advantage of also inhibiting the cellular transport of both purine and pyrimidine
      nucleosides (IC50: 2.5 microM) over a 30 s period in vitro. Hence, AQ may prevent
      the incorporation [3H]thymidine into DNA because it rapidly blocks the uptake of
      these nucleosides by the tumor cells. After 24 h, AQ induces as much DNA cleavage
      as camptothecin and DAU, two anticancer drugs producing DNA strand breaks and
      known to, respectively, inhibit topoisomerase I and II activities. However, the
      concentration-dependent induction of DNA cleavage by AQ, which peaks at 1.6-4
      microM and disappears at 10-25 microM, resembles that of DAU. The mechanism by
      which AQ induces DNA cleavage is inhibited by actinomycin D, cycloheximide and
      aurintricarboxylic acid, suggesting that AQ activates endonucleases and triggers
      apoptosis. The abilities of AQ to block nucleoside transport, inhibit DNA
      synthesis and induce DNA fragmentation are irreversible upon drug removal,
      suggesting that this compound may rapidly interact with various molecular targets
      in cell membranes and nuclei to disrupt the functions of nucleoside transporters
      and nucleic acids, and trigger long-lasting antitumor effects which persist after
      cessation of drug treatment. Because of its potency and dual effects on
      nucleoside transport and DNA cleavage, the use of bifunctional AQ with
      antileukemic activity in the nM range in vitro might provide a considerable
      advantage in polychemotherapy to potentiate the action of antimetabolites and
      sensitize multidrug-resistant tumor cells.

PMID- 10912951
TI  - Growth inhibitory effect of a new camptothecin analog, DX-8951f, on various drug
      resistant sublines including BCRP-mediated camptothecin derivative-resistant
      variants derived from the human lung cancer cell line PC-6.
AB  - DX-8951f, a new water-soluble camptothecin (CPT) derivative, has been reported to
      show potent antitumor effects against various tumors in vitro and in vivo. We
      further evaluated the cytotoxic effect of DX-8951f against eight drug-resistant
      sublines derived by stepwise exposure of human oat cell carcinoma PC-6 to various
      drugs. In paclitaxel-, adriamycin-, vincristine- and etoposide-resistant cells,
      overexpression of P-glycoprotein (P-gp) and a correlative reduction in drug
      accumulation and typical drug-sensitivity pattern were confirmed. The etoposide
      resistant line with the highest P-gp level was cross-resistant also to SN-38, CPT
      11 and topotecan (TPT), but not to 9-aminocamptothecin (9-AC), CPT and DX-8951f.
      SN-38- and CPT-11-resistant cells, of which topoisomerase I activities and levels
      were similar to those of the parent cells, showed cross-resistance clearly to
      TPT, 9-AC and mitoxantrone, but hardly to DX-8951f. In these two resistant
      sublines, the intracellular topotecan level was significantly lower than that in
      parental PC-6 and the reduced accumulation was found to be mediated by breast
      cancer resistant protein (BCRP). The cisplatin-resistant variant, which had a 2
      fold increase in glutathione content, showed no cross-resistance and the 5
      fluorouracil-resistant variant, which had a 50% decrease in glutathione content,
      exhibited collateral sensitivity to most of the other anticancer agents including
      DX-8951f. We concluded that DX-8951f showed a potent cytotoxic effect on various
      types of drug-resistant cells.

PMID- 10912952
TI  - Antiproliferative activity in vitro of new malatoplatinum(ll) complexes.
AB  - The results of studies on antiproliferative activity in vitro of nine new
      platinum(II) complexes against cells of eight human and six murine neoplastic
      cell lines are described. New complexes with the anionic rest originating from
      enantiomeric forms of hydroxydicarboxylic malic acid were synthesized to obtain
      agents with increased water solubility and decreased toxicity. Three compounds,
      coded 1-3, with ethylenediamine as a neutral ligand, showed cytotoxic activity
      against 12 out of 14 target cell lines. Their cytotoxic activity was similar or
      even slightly higher than that of the reference carboplatin. The remaining six
      compounds, coded 4-9, with 1-alkylimidazole as a neutral ligand, revealed rather
      low cytotoxic activity, and only against the cells of the human bladder cancer
      cell line Hu1703He, ovarian cancer cell line OAW-42 and mouse leukemia P388. Most
      of them appeared to be negative against all other cell lines. No compounds,
      including reference carboplatin, showed any cytotoxicity against the cells of the
      T47D human breast cancer cell line or B16F-10 mouse melanoma cell line. The
      results obtained are in accordance with common opinion, i.e. that the presence of
      neutral amine ligands with NH groups is required for the cytotoxic activity of
      platinum complexes. Compounds with a primary amine (ethylenediamine) showed
      higher cytotoxic activity in vitro than complexes with a tertiary amine
      (1alkylimidazole).

PMID- 10912953
TI  - Bovine seminal ribonuclease attached to nanoparticles made of polylactic acid
      kills leukemia and lymphoma cell lines in vitro.
AB  - Bovine seminal ribonuclease (BS-RNase) is a protein with a number of biological
      effects. It shows antitumoral, aspermatogenic, antiembryonic, immunosuppressive
      and antiviral properties. The cytotoxic effects appear to be specific for tumor
      cells as non-malignant cells seem to be unaffected in vitro. Unfortunately, the
      in vivo application of BS-RNase so far was successful only when it was
      administered intratumorally. Therefore, the objective of the present
      investigation was to improve the properties of BS-RNase by attachment to
      nanoparticles made of polylactic acid (PLA-NP) using an adsorption method. This
      preparation was tested in vitro against leukemia (MOLT-4) and lymphoma (H9) cell
      lines sensitive and resistant to cytarabine. No difference between the
      nanoparticle preparation and pure BS-RNase was found in these tests. To examine
      the in vivo effects, the preparations were tested for their aspermatogenic and
      antiembryonal efficacy compared to the pure BS-RNase as a rapid test for
      antitumoral activity. The aspermatogenic and antiembryonal effects were enhanced
      by the nanoparticle preparation. Consequently, BS-RNase loaded adsorptively to
      PLA-NP holds promise for the in vivo use as an antitumoral agent. Further
      research will investigate the efficacy of this preparations in an in vivo tumor
      model.

PMID- 10912954
TI  - Toxicity and DNA binding of dextran-doxorubicin conjugates in multidrug-resistant
      KB-V1 cells: optimization of dextran size.
AB  - We previously showed that conjugating doxorubicin to very large 70-500 kDa
      dextran decreased its removal rate from P-glycoprotein (P-gp) over-expressing,
      multidrug-resistant KB-V1 cells. Furthermore these conjugates could act
      synergistically with other cancer drugs. In the drug-sensitive 3-1 clone, but not
      in the V1 subclone which was 300-fold more resistant to free doxorubicin,
      conjugation led to a size-related decrease in toxicity. Here we identified the
      optimal size of dextran for avoiding P-gp-mediated efflux and yet preserving as
      much as possible doxorubicin toxicity. Chemically reduced, intracellularly stable
      3.4-10 kDa conjugates were prepared. Confocal microscopy and fluorescence
      quenching experiments showed that these conjugates entered nuclei and interacted
      with DNA. In 3-1 cells, but not in V1 cells, cytotoxicity of conjugates decreased
      14- to 45-fold linearly related to log size of the carrier (r=0.95). In V1 cells
      toxicity of the 10 kDa conjugate exceeded that of free doxorubicin. After
      conjugation the equilibrium binding constant of the DNA-drug complex (KA)
      decreased only by up to 3-fold. In 3-1 cells, but not in VI cells, DNA binding
      kinetics was an important factor and toxicity could be linearly correlated to
      1/KA of conjugate (r=0.94). Drug accumulation decreased with an increase in
      dextran size but drug removal was decreased only in V1 cells. It appeared that
      drug uptake was also sensitive to dextran conjugation. In Vl cells drug removal
      was sensitive to the P-gp inhibitor verapamil or energy starvation. Ratios of
      V1/3-1 toxicity, drug accumulation and drug removal correlated linearly with log
      dextran size. When these ratios equaled 1, dextran sizes were estimated to be 32,
      103 and 21 kDa, respectively.

PMID- 10912955
TI  - Effects of combretastatin A-4 prodrug against a panel of malignant human B
      lymphoid cell lines.
AB  - Combretastatin A-4 (CA-4) is one of a family of compounds isolated from the South
      African willow tree Combretum caffrum. CA-4 was found to be active against murine
      melanoma and a variety of other human solid tumors. For the first time, we report
      the effect of CA-4 against a panel of malignant human B-lymphoid cell lines
      [early pre-B acute lymphoblastic leukemia (Reh), diffuse large cell lymphoma (WSU
      DLCL2), chronic lymphocytic leukemia (WSU-CLL) and Waldenstrom's
      macroglobulinemia (WSU-WM)]. Our results indicate, using the prodrug form of CA
      4, a concentration-dependent growth inhibition in all tested cell lines, although
      WSU-DLCL2 was more sensitive. Exposure to 4 nM CA-4 for 96 h induced 77% growth
      inhibition in Reh, 86% in WSU-CLL and 92% in WSU-WM. When used against the WSU
      DLCL2 cell line, this same concentration of CA-4 was completely toxic.
      Morphological examination showed CA-4 induced the formation of giant,
      multinucleated cells, a phenomenon commonly found in mitotic catastrophe. Only
      minimal numbers of cells showing characteristics of apoptosis were detected. In
      WSU-DLCL2 cells, CA-4 (3 nM) induced the highest apoptosis (5%) after 48 h, while
      the percentage of dead cells was approximately 47%. Exposure of Reh, WSU-CLL, WSU
      WM and WSU-DLCL2 cells for 24 h to 5 nM CA-4 induced 19, 28, 57 and 75% G2/M
      arrest, as determined by flow cytometry, respectively. Based on these preliminary
      studies, we believe that mitotic catastrophe is the predominant mechanism by
      which CA-4 induces cell death rather than apoptosis. Further studies to elucidate
      the mechanisms of CA-4 activity in vitro and in vivo are currently under
      investigation in our laboratory.

PMID- 10912956
TI  - Intraperitoneal injection of dextran sulfate as an anti-adherent drug for the
      prevention of peritoneal metastasis of cancer shows low toxicity in animals.
AB  - Intraperitoneal dextran sulfate with a mean molecular weight of 5 x 10(5) has
      been developed for use in an anti-adherent therapy against peritoneal
      carcinomatosis. The present study examined acute toxicity of i.p. injection of
      dextran sulfate in mice and rabbits. The 10, 50 and 90% lethal dose values are
      0.213 (0.146-0.252), 0.336 (0.291-0.405) and 0.530 mg/g (0.431-0.873 mg/g: 95%
      confidence interval) in mice, respectively. These are markedly larger than the
      efficacious dose of 0.005-0.01 mg/g obtained previously. Death or symptoms of
      intoxication were seen within 3 days after administration of toxic doses. Rabbits
      received i.p. injection of dextran sulfate at 0.02 mg/g, which was close to the
      efficacious dose. At 2, 4, 6, 8 and 13 days after administration, blood was taken
      for biochemical and hematological analyses. Dextran sulfate at 0.02 mg/g induced
      no remarkable abnormal findings. These results suggest that the i.p. dextran
      sulfate is safe as an anti-adherent agent against peritoneal metastasis of
      cancer.

PMID- 10912957
TI  - Nitric oxide synthase inhibitor suppresses the ototoxic side effect of cisplatin
      in guinea pigs.
AB  - Cisplatin is known to cause inner ear damage (ototoxicity). The role of inducible
      nitric oxide synthase (iNOS) in the cochlea of guinea pigs after injections of
      cisplatin or a combination of cisplatin and NOS inhibitor (NG-nitro-L-arginine
      methyl ester, L-NAME) i.p. was examined electro-and immunohistochemically. The
      auditory brain stem responses (ABR) were measured prior to injection and 3 days
      after the injection. Three days after injection, the cochleas were examined
      immunohistochemically for iNOS. We found that iNOS was expressed in the cisplatin
      and L-NAME/ cisplatin-treated cochlea. The threshold shift of ABR was
      significant in the cisplatin group, whereas it was decreased in the L
      NAME/cisplatin group. iNOS catalyzed high NO levels lead to inner ear
      dysfunction. Our results indicate that iNOS mediates the ototoxicity of
      cisplatin.

PMID- 10912958
TI  - Effects of obstetrician gender on communication and patient satisfaction.
AB  - OBJECTIVE: To describe patient-obstetrician communication during the first
      prenatal visit and its relationship to physician gender and patient satisfaction.
      METHODS: The first prenatal visit of 87 women with 21 obstetricians (11 male and
      ten female) was audiotaped and analyzed using the Roter Interaction Analysis
      System. Patient satisfaction was measured by postvisit questionnaire. RESULTS:
      Communication during first prenatal visits was largely biomedical, with little
      psychosocial or social discussion. Male physicians conducted longer visits than
      females (26 minutes versus 21.9 minutes, P < .05) and engaged in more
      facilitative communication (ie, making sure they were understood and providing
      direction and orientation) and explicit statements of concern and partnership (z
      > 1.96, P < .05). Female physicians devoted more communication to agreements,
      disagreements, and laughter than males (z > 1.96, P < .05). Satisfaction with
      physicians' emotional responsiveness and informational partnership was related to
      female physician gender and a variety of task-focused and affective communication
      variables. CONCLUSION: Communication and satisfaction between women and
      obstetricians during initial prenatal visits is related to physician gender and
      patient satisfaction. Male physicians conducted longer visits but women were more
      satisfied with female physicians.

PMID- 10912959
TI  - Genetics in obstetricians' offices: a survey study.
AB  - OBJECTIVE: To investigate obstetricians' genetic knowledge base and practice
      trends. METHODS: A questionnaire survey was sent to 1003 ACOG Fellows, 554 (55%)
      of whom responded. Results from the 446 respondents practicing obstetrics are
      reported. RESULTS: The majority of obstetricians surveyed (85.6%) reported
      completing standardized genetic-history forms for prenatal patients, and about
      half (48%) performed their own invasive diagnostic procedures. Most (87%) had
      access to genetic counselors. For aneuploidy risks associated with advanced
      maternal age, up to 69% of respondents provided at least some patient counseling
      in their offices. Physician knowledge of risk assessment and diagnostic testing
      in the areas of aneuploidy and neural tube defects was very good; however, for
      single-gene disorders such as cystic fibrosis, Tay-Sachs disease, and sickle cell
      disease, correct risk assessment or appropriate test selection presented
      difficulties for at least half of the respondents. Respondents cited the rapidity
      of changes in genetic testing as the greatest obstacle to providing genetic
      information to patients. CONCLUSION: Obstetricians' knowledge of inheritance and
      test selection pertaining to single-gene disorders was more limited than that for
      aneuploidy and neural tube defects. Comparable deficits were noted in patient
      education efforts for single-gene disorders.

PMID- 10912960
TI  - Obstetricians' ability to assess the airway.
AB  - OBJECTIVES: To assess the ability of obstetricians to recognize parturients at
      risk for difficult intubation and to examine the effect of education in airway
      examination on that ability. METHODS: The airways of 160 parturients were
      examined by four physicians: one attending and one resident obstetrician, and one
      attending and one resident anesthesiologist. After each airway examination, the
      physicians completed questionnaires about possible difficult intubation, use of
      antepartum consultation, and choice of analgesia early in labor. RESULTS:
      Instruction in airway examination did not affect obstetricians' ability to assess
      airways. Compared with the attending anesthesiologist's opinion, the sensitivity
      and specificity of the attending obstetrician before instruction were 0.59 and
      0.82, respectively, and for the obstetric resident, 0.41 and 0.89, respectively.
      After instruction, the sensitivity and specificity for the obstetric attending
      physician were 0.60 and 0.83, respectively and for the obstetric resident, 0.50
      and 0.87, respectively. In airways judged possible difficult intubations by the
      obstetricians, instruction did not affect the use of antepartum consultation or
      early epidural analgesia by the residents. In the obstetric attending physicians
      there was a significant increase in use of early epidural analgesia. CONCLUSION:
      Although instruction in airway examination did not affect obstetricians' ability
      to predict difficult airways, it did affect treatment of labor analgesia.

PMID- 10912961
TI  - Population-based screening for postpartum depression.
AB  - OBJECTIVE: To estimate the community prevalence in Olmsted County, Minnesota of
      elevated scores on the Edinburgh Postnatal Depression Scale, a self-report
      screening tool for postpartum depression. METHODS: At the 6-week postpartum
      visit, the Edinburgh Postnatal Depression Scale was administered to women who
      gave birth in Olmsted County between July 28, 1997 and March 28, 1998. Study
      sites included all ambulatory clinics that provide pregnancy care in the county,
      and women who missed postpartum visits were contacted by mail. A threshold of 12
      or more points on the scale was selected for clinical use; data for scores of ten
      and above were also examined. RESULTS: Of the 909 Olmsted County women studied
      (response rate 83.2%), 11.4% (n = 104) had scores of 12 or greater, with a 95%
      confidence interval (CI) of 9.4%, 13.5%. The percentage of women with a positive
      screen increased to 19.8% (n = 180; 95% CI 17.2%, 22.4%) when scores of 10 or
      higher were included, as has been recommended for screening in primary care
      settings. Forty-eight or 5.3% of the subjects (95% CI 3.8%, 6.7%) indicated
      experiencing suicidal ideation during the previous week. CONCLUSION: More than
      11% of women had elevated scores on the Edinburgh Postnatal Depression Scale,
      indicating a high likelihood of postpartum depression and the need for further
      assessment. The screening process required little extra time and was acceptable
      to the subjects and clinicians. Screening for postpartum depression is
      appropriate and feasible for clinical practice and increases the identification
      of women suffering from this serious, common, and highly treatable disorder.

PMID- 10912962
TI  - Increased risk of cytomegalovirus transmission in utero during late gestation.
AB  - OBJECTIVE: To determine whether the rate of human cytomegalovirus transmission in
      utero is related to the gestational age at the time of maternal infection.
      METHODS: One hundred twenty-three pregnant women followed in our units between
      1988 and 1998 were studied retrospectively. Each had developed a primary
      infection with cytomegalovirus evidenced by a seroconversion, confirmed by
      specific enzyme immunoassays. Infants were diagnosed by urine culture. RESULTS:
      Regardless of gestational age at the time of maternal cytomegalovirus
      seroconversion, the mean rate of intrauterine transmission was 57.5%. There was a
      statistically significant difference between early seroconversion (during the
      first trimester) and late seroconversion (during the third trimester) (36.0%
      versus 77.6%; P < .001). The risk of transmission calculated for seroconversion
      during the second trimester was intermediate (44.9%). CONCLUSION: A statistically
      significant difference in the rate of intrauterine cytomegalovirus transmission
      was observed according to the duration of pregnancy at which primary infection
      occurred. The rate of transmission increased with gestational age.

PMID- 10912963
TI  - Physical violence during pregnancy: maternal complications and birth outcomes.
AB  - OBJECTIVE: To assess the association between physical violence during the 12
      months before delivery and maternal complications and birth outcomes. METHODS: We
      used population-based data from 6143 women who delivered live-born infants
      between 1993 and 1995 in South Carolina. Data on women's physical violence during
      pregnancy were based on self-reports of "partner-inflicted physical hurt and
      being involved in a physical fight." Outcome data included maternal antenatal
      hospitalizations, labor and delivery complications, low birth weights, and
      preterm births. Odds ratios and 95% confidence intervals were calculated to
      measure the associations between physical violence, maternal morbidity, and birth
      outcomes. RESULTS: The prevalence of physical violence was 11.1%. Among women who
      experienced physical violence, 54% reported having been involved in physical
      fights only and 46% had been hurt by husbands or partners. In the latter group,
      70% also reported having been involved in fighting. Compared with those not
      reporting physical violence, women who did were more likely to deliver by
      cesarean and be hospitalized before delivery for maternal complications such as
      kidney infection, premature labor, and trauma due to falls or blows to the
      abdomen. CONCLUSION: Physical violence during the 12 months before delivery is
      common and is associated with adverse maternal conditions. The findings support
      the need for research on how to screen for physical violence early in pregnancy
      and to prevent its consequences.

PMID- 10912964
TI  - Management of pregnancies complicated by anti-Kell isoimmunization.
AB  - OBJECTIVE: To assess the efficacy of managing pregnancies complicated by anti
      Kell isoimmunization using the methods developed for evaluating anti-Rh-D
      isoimmunization. METHODS: We reviewed 156 anti-Kell-positive pregnancies seen
      from 1959 to 1995, which were managed with serial maternal titers, amniotic fluid
      deltaOD450 determination, and funipuncture. Data on maternal titers, paternal
      phenotypes, invasive fetal testing and therapies, and neonatal outcomes were
      collected and analyzed to determine whether severely affected pregnancies were
      identified in time for successful fetal and neonatal therapy. RESULTS: Twenty-one
      fetuses were affected, eight with severe disease, and two fetuses in this group
      died. All of the severely affected fetuses were associated with maternal serum
      titers of at least 1:32. A critical titer of 1:32 was found to be 100% sensitive
      for identifying the affected pregnancies. The affected group had significantly
      higher amniotic fluid deltaOD450 values over the range of gestational ages than
      did the unaffected group (P < .001). The upper Liley curve was a specific
      discriminator for the diagnosis of affected fetuses, and the lower curve was
      specific for the diagnosis of unaffected or mild cases. CONCLUSION: Fetal anemia
      due to anti-Kell isoimmunization might be due in part to erythropoietic
      suppression, but it is still largely a hemolytic process. The methods based on a
      hemolytic process, including use of a critical maternal serum titer of 1:32,
      serial amniotic fluid analyses when the titer was exceeded, and liberal use of
      funipuncture, were successful in identifying severely affected fetuses.

PMID- 10912965
TI  - Vaginal birth after cesarean: an appraisal of fetal risk.
AB  - OBJECTIVE: To expand on prior investigations and further evaluate the fetal risk
      associated with vaginal birth after cesarean (VBAC) by examining the incidence
      not only of a depressed Apgar score at 5 minutes but also of fetal acidemia.
      METHODS: Between January 1, 1991, and December 31, 1996, the following groups of
      patients who delivered a singleton fetus with birth weight greater than 750 g
      were identified: 2082 patients with one or more prior cesarean deliveries who
      were allowed a trial of labor, 1677 of whom delivered vaginally and 405 of whom
      delivered by repeat cesarean; 920 patients delivered by elective repeat cesarean;
      22,863 patients without a prior cesarean who delivered vaginally; and 2432
      patients delivered by primary cesarean after laboring. Umbilical cord arterial
      blood gases were obtained in 88.3% of these deliveries. Comparisons of Apgar
      scores at 5 minutes and umbilical cord arterial pH measurements were made between
      groups with chi2 or Fisher exact test, and odds ratios (ORs) were calculated.
      RESULTS: The only significant differences were noted between those patients who
      delivered vaginally after a prior cesarean and those patients who delivered
      vaginally without a prior cesarean. Neonates in the successful VBAC group were
      more likely to have an Apgar score at 5 minutes less than 7 (OR 1.52) or an
      umbilical arterial pH less than 7.1 (OR 1.69). Those neonates, however, were not
      at greater risk for an Apgar score less than 4 or a pH less than 7.0. CONCLUSION:
      Our experience suggests that VBAC poses a low level of fetal risk, although a
      much larger sample size would be required to exclude a two-fold increase in
      potentially damaging fetal acidemia.

PMID- 10912966
TI  - Fetal amino acid and enzyme levels with maternal smoking.
AB  - OBJECTIVE: To assess the influence of active maternal smoking on fetal amino acid
      and enzyme levels in early pregnancy. METHODS: The concentrations of 23 free
      amino acids and total protein, and the activity levels of four enzymes were
      measured in samples of maternal and fetal plasma from nine nonsmokers who were
      not exposed to tobacco smoke and nine long-term, heavy smokers matched for
      gestational age. To determine fetal exposure to smoking, cotinine levels were
      measured in maternal and fetal plasma and fetal liver samples from both groups.
      The pregnancies were between 12 and 17 weeks' gestation. RESULTS: In women who
      smoke, the median cotinine concentrations were 156 mg/mL in maternal plasma and
      89 ng/mL in fetal plasma, but only one fetal liver sample contained detectable
      cotinine. Significantly lower concentrations of serine, proline, alpha
      aminobutyric acid, leucine, and arginine were found in smokers compared with
      nonsmokers, with the lowest in arginine. Fetal plasma amylase activity was
      significantly higher in smokers than controls. There were no differences in
      concentrations of other amino acids or activity levels of other enzymes in the
      two groups. CONCLUSION: Maternal smoking affected placental and fetal protein
      metabolism and enzyme activity from at least 12 weeks' gestation. That finding
      indicates that high levels of tobacco exposure in the first trimester might cause
      irreversible changes in the cellular functions of the villous trophoblastic
      barrier.

PMID- 10912967
TI  - Intra-amniotic bleeding and fetal echogenic bowel.
AB  - OBJECTIVE: To assess the relationship between intra-amniotic bleeding and fetal
      echogenic bowel. METHODS: Comprehensive fetal ultrasound examinations were done
      before and 12 hours after fetal transfusions. Follow-up ultrasound examinations
      were done weekly in 28 fetuses with intra-amniotic bleeding. Hyperechogenic bowel
      was diagnosed when the echogenicity of fetal bowel was similar to that of bone.
      Postpuncture bleeding was identified when a stream of echogenic material from the
      cord into the amniotic space was seen, lasting at least 60 seconds. RESULTS: None
      of the fetuses had echogenic bowel before initial transfusions. Intra-amniotic
      bleeding was followed by bowel echogenicity in seven of 28 fetuses within the
      first 12 hours after bleeding episodes. Echogenic bowel remained in five fetuses
      2 weeks after the bleeding episodes. In three fetuses, echogenic bowel was still
      seen 4 weeks later. CONCLUSION: Intra-amniotic bleeding can lead to echogenic
      bowel.

PMID- 10912968
TI  - Detection of growth-restricted fetuses in preeclampsia: a case-control study.
AB  - OBJECTIVE: To determine the diagnostic accuracy of detecting growth-restricted
      fetuses in women with and without preeclampsia. METHODS: Over 2 years,
      parturients with reliable gestational ages, preeclampsia, and sonographic
      estimates of birth weights were matched (1:1) for gestational age with women
      without preeclampsia. Paired and unpaired t tests were used; P < .05 was
      significant. Odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated. RESULTS: Two hundred eighty-seven preeclamptic women were identified
      and matched. In each group, mean (+/- standard deviation [SD]) gestational age
      was 34.9 +/- 4.2 weeks, and 166 (57.8%) infants were born preterm. Fetal growth
      restriction (FGR) was significantly more common among women with preeclampsia
      (14.9%) than among controls (5.6%; OR 2.98, 95% CI 1.64, 5.44). The percentage of
      sonographic estimates within 10% of actual birth weight (57.5% versus 53.6%) was
      similar in the two groups (OR 1.16; 95% CI 0.84,1.62). Compared with normal
      growth, the mean (+/- SD) standardized absolute error was significantly higher
      among those with FGR regardless of group (preeclampsia 109 +/- 100 versus 158 +/-
      152 g/kg; P = .009; control 117 +/- 103 versus 233 +/- 206 g/kg; P < .001). Fetal
      growth restriction was detected more commonly among preeclamptic women than among
      controls (11.6% versus 0%; OR 4.74 95% CI 0.25, 90.31). The sensitivity and
      positive predictive value of FGR detection were 10% and 50%, respectively, among
      women with preeclampsia and 0% each among controls. CONCLUSION: Although FGR was
      detected more frequently in fetuses of women with preeclampsia than in those of
      controls, the ability to predict it with sonography remained poor.

PMID- 10912969
TI  - Comparison of three sonographic circumference measurement techniques to predict
      birth weight.
AB  - OBJECTIVE: To compare the accuracy of three different sonographic circumference
      measurement techniques in predicting birth weight in term fetuses, using a
      standard equation for estimating fetal weight. METHODS: Fifty-three singleton,
      term fetuses were examined sonographically within 24 hours of scheduled elective
      cesarean delivery. The biparietal diameter (BPD) and femur length (FL) were
      measured using standard techniques, and head circumference (HC) and abdominal
      circumference (AC) were measured using three separate circumference measurement
      techniques (Two-diameter, ellipse, and trace). With the use of each circumference
      method, estimated fetal weights were determined for each fetus according to a
      weight-estimation formula incorporating BPD, HC, AC, and FL. The accuracy of the
      formula using each circumference measurement technique for predicting actual
      birth weight was calculated. RESULTS: The mean (+/- standard deviation [SD])
      gestational age was 38.1 +/- 0.9 weeks and the mean actual birth weight was 3536
      +/- 472 g. The two-diameter and ellipse circumference measurements allowed more
      accurate birth weight prediction than did the trace method, with mean (+/- SD)
      percent deviations from the actual birth weight of -0.5 +/- 7.8%, 1.9 +/- 8.0%,
      and 8.2 +/- 11.6% (P < .05), respectively. The trace method was the least
      accurate, with a mean birth weight overestimation of 266 g and measurements
      within 10% of the actual birth weight only 49.1% of the time. The two-diameter
      and ellipse method yielded predicted birth weights within 10% of actual birth
      weights in 77.4 and 79.2% of cases, respectively. CONCLUSION: Two-diameter and
      ellipse circumference measurement techniques are similarly accurate in predicting
      birth weight and both are significantly better than the trace technique.

PMID- 10912970
TI  - Transvaginal Doppler assessment of fetal intracranial venous flow.
AB  - OBJECTIVE: To investigate physiologic blood-flow-velocity waveform patterns of
      the fetal cerebral venous system during normal pregnancies by transvaginal
      Doppler studies and to evaluate cases with abnormal venous-flow patterns.
      METHODS: Internal cerebral veins and the three dural sinuses, those of the
      superior sagittal sinus, vein of Galen, and straight sinus, were examined in
      normal cephalic-presenting fetuses of 20-40 weeks' gestation. For analysis, the
      venous index was defined as maximum minus minimum velocity divided by maximum
      velocity. Different cases with intracranial abnormalities were evaluated with
      emphasis on abnormal venous blood-flow patterns. RESULTS: Internal cerebral veins
      had pulsatile patterns with a venous index of 0.22 in 47.6% of fetuses, whereas
      all fetuses had pulsations in the dural sinuses. The vein of Galen had a
      significantly lower venous index (0.31) than the superior sagittal sinus (0.39)
      and the straight sinus (0.36), indicating that the amplitude of the intracranial
      venous pulsation might increase as the flow runs from the periphery toward the
      proximal portion. Significant regression lines of venous index were obtained,
      indicating the stability of the pulsation during pregnancy. A flat pattern of
      superior sagittal sinus flow was found in three cases of hydrocephalus and one of
      craniosynostosis. CONCLUSION: We showed the normal patterns of fetal cerebral
      venous blood-flow velocity and the abnormal patterns which might be associated
      with increased intracranial pressure. Doppler assessment of the intracranial
      venous system enabled us to evaluate intracranial abnormalities accompanied by
      increased intracranial pressure that might have prognostic clinical importance.

PMID- 10912971
TI  - Sonographic identification of fetuses with Down syndrome in the third trimester:
      a matched control study.
AB  - OBJECTIVE: To determine sonographic findings in Down syndrome fetuses in the
      third trimester. METHODS: Down syndrome fetuses who had third-trimester
      ultrasound examinations between 25 and 41 weeks' gestation were matched for
      gestational age with three controls each. Fetal structural anomalies, Down
      syndrome dysmorphology markers (abnormal facial profile, sandal gap, tongue
      thrusting, clinodactyly, or hypoplastic middle phalanx of the fifth finger), and
      abnormal long-bone biometry (femur, humerus, tibia, and fibula; femur length to
      biparietal diameter ratio; and femur length to abdominal circumference ratio were
      abstracted from the ultrasound reports. The fetal face, hands, feet, profile, and
      cardiac outflow tracts are routinely evaluated in our center. RESULTS: Seventeen
      fetuses with Down syndrome who had third-trimester ultrasound evaluations were
      identified. Anomalies included cardiac defects (five), tongue thrusting (three),
      clinodactyly (three), abnormal profile (three), sandal gap (two), and duodenal
      atresia (two). Of the 17 fetuses, at least one long-bone abnormality was found in
      13, at least one structural or biometric anomaly was found in 15, and at least
      two abnormal findings existed in 11. Abnormal ultrasound findings, including
      structural anomalies, short bones, and Down syndrome dysmorphology markers, were
      more common in cases than in matched controls. CONCLUSION: At least one abnormal
      ultrasound finding was present in 15 of 17 fetuses, and abnormal bone
      measurements or ratios were discovered in 13 of 17. Abnormal long-bone biometry
      at third-trimester ultrasound should raise the suspicion of fetal Down syndrome.

PMID- 10912972
TI  - Maternal serum screening for fetal trisomy 18: a comparison of fixed cutoff and
      patient-specific risk protocols.
AB  - OBJECTIVE: To compare the effectiveness of two widely used protocols for second
      trimester screening for fetal trisomy 18. METHODS: Second-trimester screening
      results for 41,565 women were reviewed to determine whether pregnancies could be
      considered to be at high risk for trisomy 18. The screening test was considered
      positive if either maternal serum concentrations of alpha-fetoprotein (MSAFP),
      hCG, and unconjugated estriol (E3) fell below defined levels, or the second
      trimester patient-specific risk (based on maternal age and serum analytes) was
      greater than 1:100. Detection rates, false-positive rates, and pregnancy outcomes
      for the two protocols were compared. RESULTS: The fixed-cutoff method showed a
      23% detection rate and a 0.19% false-positive rate for trisomy 18. These low
      rates were in close agreement with a theoretical expectation for fixed-cutoff
      trisomy 18 screening. The risk-based approach resulted in a 69% detection rate
      and a 0.45% false-positive rate. Both methods identified pregnancies with other
      fetal anomalies. CONCLUSION: Overall, the risk-based method is more effective
      than the fixed-cutoff approach to trisomy 18 screening.

PMID- 10912973
TI  - Prior knowledge of obstetric gestational age and possible bias of Ballard score.
AB  - OBJECTIVE: To determine whether prior knowledge of obstetric estimate of
      gestational age creates a bias in assignment of gestational age by the Ballard
      assessment score. METHODS: The Ballard assessment score was done on 82 infants
      weighing less than 2500 g by two examiners, one who had prior knowledge of best
      obstetric gestational age estimate and the other who was masked to that
      information. Obstetric gestational age was correlated with masked and unmasked
      score. Statistical analysis used Spearman rank correlation test, plotting the
      measurement means against the measurement differences, chi2, Wilcoxon signed-rank
      test, analysis of variance, and Student t test. Significance was assumed at P <
      .05. RESULTS: There was high reliability (r = 0.84-0.86) between obstetric
      gestational age estimates (33.3 +/- 3.0 weeks) and the gestational age derived
      from masked (34.3 +/- 3.0 weeks) and unmasked (34.0 +/- 3.0 weeks) Ballard
      scores. The mean difference between unmasked scores and gestational age was 1.38
      +/- 1.15 weeks and that between masked scores and obstetric gestational age was
      1.40 +/- 1.15 weeks, a nonsignificant difference. There was no significant
      difference in the number of cases with 100% agreement between masked and unmasked
      scores and obstetric gestational age or in the number of cases in which the score
      (masked or unmasked) differed by more than 2 weeks from obstetric gestational
      age. This study had over 99% power to detect a 1-week difference between the
      accuracy of masked and unmasked scores. CONCLUSION: Prior knowledge of obstetric
      gestational age did not bias the Ballard assessment score.

PMID- 10912974
TI  - Gestational bleeding, bacterial vaginosis, and common reproductive tract
      infections: risk for preterm birth and benefit of treatment.
AB  - OBJECTIVE: To examine associations between bacterial vaginosis and other
      prevalent lower genital tract infections and clinically recognized first
      trimester bleeding; possible independent and joint effects of gestational
      bleeding and bacterial vaginosis or other prevalent infections on preterm birth
      and premature rupture of membranes; and effects of antimicrobial treatment on
      reducing risks of preterm birth among these women. METHODS: A secondary analysis
      was conducted of 1100 pregnant women enrolled in a prospective observational
      study that examined the effects of standardized diagnosis and treatment of lower
      genital tract infections to prevent preterm birth. RESULTS: Sixty percent of
      women with first-trimester bleeding had one or more study infections detected at
      the initial examination. First-trimester bleeding was associated independently
      with the presence of bacterial vaginosis (odds ratio [OR] 1.5, 95% confidence
      interval [CI] 1.0, 2.3), Trichomonas vaginalis (OR 2.3, 95% CI 1.3, 4.2), and
      Chlamydia trachomatis (OR 2.7, 95% CI 1.4, 5.1). Preterm birth was increased
      among women with first-trimester bleeding and bacterial vaginosis (relative risk
      [RR] 4.4, 95% CI 2.0, 9.5) and bacterial vaginosis and T vaginalis (RR 3.0, 95%
      CI 1.0, 8.8). Systemic antimicrobial treatment reduced the rate of preterm birth
      among women with bacterial vaginosis without first-trimester bleeding (RR 0.37,
      95% CI 0.16, 0.88). Treatment of women with both first-trimester bleeding and
      bacterial vaginosis reduced preterm birth (RR 0.52, 95% CI 0.18, 1.55), but not
      significantly. CONCLUSION: First-trimester bleeding was increased among women
      with bacterial vaginosis, T vaginalis, C trachomatis, and combinations of these
      infections. Women with bacterial vaginosis who also experienced first-trimester
      bleeding were at heightened risk for preterm birth. Treatment of studied
      infections reduced significantly the risks of preterm birth among women without
      first-trimester bleeding.

PMID- 10912975
TI  - Prevention of preeclampsia: a randomized trial of atenolol in hyperdynamic
      patients before onset of hypertension.
AB  - OBJECTIVE: To determine if assessment of maternal hemodynamics could predict
      women at risk for the development of preeclampsia, if treatment directed at
      hemodynamic abnormalities before the onset of hypertension could prevent
      preeclampsia, and if mothers could be treated in a way that protects fetal
      growth. METHODS: A double-blinded, randomized controlled trial was conducted.
      Subjects were considered to be at risk for preeclampsia if their cardiac output
      was greater than 7.4 L/min before 24 weeks' gestation. Nulliparous and diabetic
      subjects at risk were treated with 100 mg of atenolol or placebo. Cardiac output
      was measured by Doppler technique. Inulin and para-aminohippurate clearances were
      performed. RESULTS: Treatment with atenolol reduced the incidence of preeclampsia
      from 5 of 28 (18%) to 1 of 28 (3.8%), (P = .04). Nulliparous women determined to
      be at risk for preeclampsia were similar to diabetic women at risk. Each was
      significantly heavier and had inulin and para-aminohippurate clearances greater
      than the control group. Treatment with atenolol was associated with infants
      weighing 440 g less than infants in the nulliparous placebo group, (P = .02). No
      effect on birth weight was seen in the diabetic patients. Mothers of the smallest
      infants who were treated with atenolol could be identified by unexpectedly large
      reductions in cardiac output. CONCLUSION: Measurement of cardiac output in the
      second trimester identified women at risk for preeclampsia. Treatment with
      atenolol decreased the incidence of preeclampsia. Nulliparous and diabetic women
      at risk for preeclampsia were similar with regard to maternal hemodynamics,
      maternal weight, and renal function. Treatment with atenolol was associated with
      reduced infant birth weight.

PMID- 10912976
TI  - Failure to obtain follow-up testing for gestational diabetic patients in a rural
      population.
AB  - OBJECTIVE: To determine physician and patient compliance rates for diabetes
      testing in patients with previous gestational diabetes. METHODS: Questionnaires
      regarding follow-up testing and personal health history were sent to 66 patients
      with previous gestational diabetes who did not have diabetes when they
      participated in a follow-up study conducted 5 years earlier. A 2-hour glucose
      tolerance test (GTT) was offered to those whose last test was done more than 1
      year previously. RESULTS: All 66 individuals returned the questionnaire and 20
      (30.3%) reported having received a yearly 2-hour GTT. Of the remaining 46, 19 had
      been tested at least once in the previous 5 years, but 27 had not been tested. Of
      the patients who had been tested at least once in the 5-year period, their
      physicians initiated testing 61.5% of the time and the patients initiated the
      remainder. There were no significant differences between physician specialty and
      rate or appropriateness of the testing. Of 39 individuals who had been tested at
      least once in the 5-year period, eight had diabetes and four were glucose
      intolerant. Of 12 individuals who had not been tested in the past year and agreed
      to be tested in 1995, four had diabetes and two had glucose intolerance.
      CONCLUSION: Although physicians and their gestational diabetic patients knew the
      risks of diabetes development, compliance with follow-up testing was poor and the
      risk of developing diabetes high.

PMID- 10912977
TI  - Selective screening for gestational diabetes mellitus in adolescent pregnancies.
AB  - OBJECTIVE: It is unclear whether it is cost-effective to universally screen
      adolescent gravidas for gestational diabetes mellitus (GDM). Our objective was to
      identify the prevalence of gestational diabetes in our adolescent population and
      to review risk factors that would most easily identify a subset of adolescent
      patients at greatest risk for the development of gestational diabetes. METHODS:
      Six hundred thirty-two adolescents were identified from 11,486 deliveries in our
      institution through International Classification of Diseases (9th edition) codes.
      Eleven of those adolescents had GDM. Their charts and those of a representative
      group of nondiabetic adolescent gravidas were analyzed for GDM risk factors,
      including race/ethnicity, body mass index (BMI), family history of diabetes,
      other medical disorders, and previous history of GDM, macrosomia, stillbirths, or
      anomalous fetus. Statistical analyses used chi2 and Student t tests as
      appropriate. RESULTS: The prevalence of GDM among adolescent gravidas was 1.7%.
      No difference was identified between the adolescent pregnancies with GDM and the
      comparison group for race/ethnicity, family history, or presence of medical
      disorders. Risk factors requiring a previous obstetric history could not be
      evaluated adequately because of the high prevalence of nulliparas. There was a
      higher prevalence of BMI over 27 in adolescents with GDM (P < .001). CONCLUSION:
      Body mass index is an important risk factor for the development of gestational
      diabetes in adolescent gravidas. We recommend that selective screening for GDM of
      adolescent gravidas be performed on the basis of BMI.

PMID- 10912978
TI  - Long-term results of hysteroscopic myomectomy for abnormal uterine bleeding.
AB  - OBJECTIVE: To analyze the efficacy of transcervical resection of submucous myomas
      and to identify prognostic factors for long-term results. METHODS: Two-hundred
      eighty-five women were treated with transcervical resection of submucous myomas
      without endometrial ablation. In case of incomplete resection a repeat procedure
      was offered. Long-term follow-up was obtained. Recurrence was defined as the need
      for further surgery. The relation of several variables with the outcome was
      analyzed using Cox proportional hazard regression analysis. RESULTS: Seventeen
      cases (6%) were lost to follow-up. The median follow-up was 46 months (range 1
      104 months); for cases without recurrence median follow-up was 42 months (range
      16-104 months). Forty-one (14.5%) patients had repeat surgery. An independent
      prognostic value of uterine size (P < .001) and number of submucous myomas (P <
      .001) for recurrence was noted. Twenty of 41 patients who had repeat surgery
      subsequently had a hysterectomy. None of the variables investigated predicted the
      need for hysterectomy. The surgery-free percentage of 165 patients with normal
      sized uteri and not more than two myomas was 94.3% (standard error +/- 1.8%) at 2
      years and 90.3% (+/- 3.0%) at 5 years. CONCLUSION: Transcervical resection of
      submucous myomas is a safe and effective treatment for patients with a normal
      sized uterus and not more than two myomas. It is an acceptable alternative for
      selected other patients. The need for a combined endometrial ablation is
      questionable. Transcervical resection of submucous myomas will give patients a
      high chance of averting further surgery and should modify the way patients are
      counseled.

PMID- 10912979
TI  - Randomized trial of antibiotic prophylaxis for combined urodynamics and
      cystourethroscopy.
AB  - OBJECTIVE: To determine the efficacy of prophylactic nitrofurantoin in preventing
      bacteriuria after urodynamics and cystourethroscopy. METHODS: We assumed that
      nitrofurantoin prophylaxis would decrease the rate of infection after urodynamics
      and cystourethroscopy from 19% to 5%. All women presenting for urodynamics and
      cystourethroscopy during a 27-month period were offered enrollment, and 142 were
      randomly assigned to receive two doses of long-acting nitrofurantoin 100 mg (n =
      74), or two doses of placebo (n = 68). Nitrofurantoin and placebo capsules were
      identical, and subjects and physicians were masked to group assignment.
      Differences were assessed using Student t test for continuous data and chi2
      analysis for dichotomous data. RESULTS: There were no statistical differences in
      demographic characteristics or final diagnoses between groups. Seven women (5%)
      who had bacteriuria on initial urine culture were not included in the final
      analysis. The frequency of bacteriuria in the postinstrumentation urine cultures
      was 6% overall, 7% in the treatment group, and 5% in the controls, a
      nonsignificant difference ([relative risk] 1.49, [confidence interval] 0.37,
      5.95). The power of the study was 33% to detect a significant difference.
      CONCLUSION: Bacteriuria after combined urodynamics and cystourethroscopy was not
      improved by a 1-day course of nitrofurantoin.

PMID- 10912980
TI  - Body mass index and outcome of incontinence surgery.
AB  - OBJECTIVE: To analyze the influence of body mass on the outcome of surgery for
      urinary incontinence. METHODS: Among 291 women operated on for stress
      incontinence, 187 (64%) were available for follow-up at 5 years. Eighty women had
      anterior colporrhaphy, 49 anterior colporrhaphy with needle suspension of the
      bladder neck, and 58 Burch colposuspension. Body mass index was calculated
      preoperatively and at follow-up. Women were classified as being of normal weight
      (body mass index [BMI] 20-25), overweight (BMI 26-30), or obese (BMI greater than
      30). Reported continence rates were analyzed according to BMI for each operation
      and the BMIs of continent patients were compared with those of incontinent
      patients. RESULTS: The continence rates at 5-year follow-up for anterior
      colporrhaphy, anterior colporrhaphy with needle suspension of bladder neck, and
      Burch colposuspension were 58, 51, and 86%, respectively (P < .001). The
      continence rates did not differ significantly among the three BMI groups for each
      procedure. A statistical power of 26% was found for the hypothesis that the
      outcome of the procedures does not depend on BMI. The preoperative and
      postoperative BMIs of continent and incontinent women for each procedure did not
      differ significantly. CONCLUSION: We did not find preoperative obesity to be a
      risk factor for failure of incontinence surgery, but the power of our study was
      limited.

PMID- 10912981
TI  - A simple system to determine who needs osteoporosis screening.
AB  - OBJECTIVE: To define factors that identify patients at highest risk for
      osteoporosis who should be screened. METHODS: We gave a questionnaire we
      developed for osteoporosis risk factors to 1346 menopausal women who were being
      screened by bone densitometry at the spine, hip, and femoral neck. Chi-square
      analysis using the one-tailed test was done on all categoric variables to
      determine differences or patterns in bone mineral density at specific sites.
      Multivariate logistic regression analysis was done on each of the three sites
      scanned to determine which combination of independent variables was a significant
      predictor of the presence or absence of osteoporosis. RESULTS: Factors identified
      that were significant for the presence of osteoporosis were age 61 years or
      older, weight 165 pounds or less, or lack of any use of estrogen, either oral
      contraceptives or estrogen replacement therapy. CONCLUSION: We devised a simple
      system to identify which patients should be screened for osteoporosis.

PMID- 10912982
TI  - Vascular endothelial growth factor in cervical carcinoma.
AB  - OBJECTIVE: To quantitate vascular endothelial growth factor of cervical carcinoma
      and elucidate its clinical correlation. METHODS: Intratumoral protein levels of
      vascular endothelial growth factor were measured in 104 cervical cancer patients
      and in 30 cervical tissue specimens of benign gynecologic diseases as controls.
      The concentrations were correlated with clinical and pathologic characteristics.
      RESULTS: The median concentrations of vascular endothelial growth factor in
      cervical cancer tissues were higher than those in benign cervical tissues (180.0
      versus 0.0 pg/mg of protein, P < .001). Tumors larger than 4 cm (1030.0 versus
      118.0 pg/mg of protein, P < .001) and with deep stromal invasion (364.0 versus
      111.0 pg/mg of protein, P = .016) had higher levels than those smaller than 4 cm
      or with superficial stromal invasion. Higher levels were also found in tumors
      with lymphovascular emboli (568.0 versus 118.0 pg/mg of protein, P = .006),
      parametrial invasion (582.0 versus 117.0 pg/mg of protein, P = .04), and pelvic
      lymph node metastasis (759.5 versus 121.0 pg/mg of protein, P = .002) than in
      those without. The protein levels of vascular endothelial growth factor
      correlated positively with tumor sizes (r = 0.340, P < .001). Tumors with
      overexpressed VEGF were larger (3.35 +/- 1.17 versus 2.13 +/- 1.28 cm, P < .001)
      and had higher incidence of deep stromal invasion (20 of 57 versus 6 of 47, P =
      .009), lymphovascular emboli (15 of 33 versus 11 of 71, P = .011), parametrial
      invasion (15 of 32 versus 11 of 72, P = .002), and lymph node metastasis (10 of
      20 versus 16 of 84, P = .004). CONCLUSION: Intratumoral protein level of vascular
      endothelial growth factor in cervical cancer tissue correlates well with local
      tumor progression and tumor metastasis. Vascular endothelial growth factor might
      be a marker for evaluating disease severity.

PMID- 10912983
TI  - A randomized controlled trial of laminaria, oral misoprostol, and vaginal
      misoprostol before abortion.
AB  - OBJECTIVE: To compare the efficacy and acceptability of oral misoprostol, vaginal
      misoprostol, and laminaria tents for cervical dilation before surgical abortion.
      METHODS: We conducted a randomized, double-blind, placebo-controlled trial
      comparing oral misoprostol 400 microg, vaginal misoprostol 400 microg, and one
      medium laminaria for dilating the cervix over 4 hours before surgical abortion.
      The study sample consisted of 106 women at 7-14 weeks' gestation who presented to
      San Francisco General Hospital requesting abortion. The primary outcome was the
      amount of cervical dilation measured by Pratt dilators. Secondary outcomes were
      the proportion of subjects needing further manual dilation, difficulty of
      dilation, duration of the procedure, blood loss, and side effects. RESULTS: The
      vaginal-misoprostol group had a significantly greater mean dilation (28.0 mm)
      than the oral misoprostol group (24.2 mm; P < .05) and a greater mean dilation
      than the laminaria group (25.9 mm), although this difference did not reach
      significance. Women who received laminaria reported significantly more pain at
      the time of placement (85.7% reported at least "a little" pain) compared with
      women who received misoprostol by either route (28.9% of oral-misoprostol and
      34.0% of vaginal-misoprostol subjects reported "a little" pain; P < .01). The
      proportion of subjects who required further manual dilation, ease of dilation,
      duration of the procedure, and blood loss were not significantly different among
      the groups. There was no difference in side effects during the 4-hour waiting
      period among the three groups, and gastrointestinal side effects were rare in all
      groups. CONCLUSION: Vaginal misoprostol is superior to oral misoprostol and is an
      acceptable alternative to laminaria tents for cervical dilation before surgical
      abortion in pregnancies of 7-14 weeks' gestation. It is inexpensive and easy to
      administer, and achieves equal or greater dilation with less pain on insertion
      and no increase in side effects compared with laminaria.

PMID- 10912984
TI  - Evaluation of the readability of ACOG patient education pamphlets. The American
      College of Obstetricians and Gynecologists.
AB  - OBJECTIVE: To evaluate whether ACOG's patient education pamphlets comply with the
      recommended readability level for health education materials intended for the
      general public. METHODS: All 100 English-language pamphlets available during 1997
      (created or revised between 1988 and 1997) were evaluated using four standard
      readability formulas. RESULTS: Mean readability levels of ACOG's pamphlets were
      between grade 7.0 to grade 9.3, depending on the formula used. Analysis of
      readability over the 10 years showed a trend toward lower readability levels.
      Analysis by category of pamphlet found that the lowest readability levels were in
      "Especially for teens" pamphlets. CONCLUSION: Our data suggested that most of
      ACOG's patient education pamphlets currently available are written at a higher
      readability level than recommended for the general public. The readability of
      those pamphlets improved in the 10 years since the organization published its
      first pamphlet, but the goal of sixth-grade readability level has not been
      reached.

PMID- 10912985
TI  - Topical lidocaine-prilocaine versus lidocaine for neonatal circumcision: a
      randomized controlled trial.
AB  - OBJECTIVE: To evaluate epicutaneous application of 5% lidocaine-prilocaine and
      30% lidocaine cream anesthetics for neonatal circumcision. METHODS: The efficacy
      of 5% lidocaine-prilocaine and 30% lidocaine creams was compared in a randomized,
      double-blind, placebo-controlled trial. Sixty-one neonates were randomly assigned
      to one of three groups: 5% prilocaine-lidocaine (n = 20), 30% lidocaine (n = 20),
      and a control group that received an acid-mantle cream (n = 21). Heart rate,
      oxygen saturation, and crying time were monitored before, during, and after
      circumcision. Blood pressure was measured before and after circumcision. RESULTS:
      Mean peak heart rates for the 5% lidocaine-prilocaine, 30% lidocaine, and control
      groups (+/- standard deviation) were 146 +/- 16, 157 +/- 10, and 164 +/- 16 beats
      per minute, respectively. During four of six active phases of circumcision, the
      5% lidocaine-prilocaine group suppressed significant increases in heart rate
      better than 30% lidocaine, which was more effective than control (dorsal clamp, P
      < .001; bell clamp on, P = .001; tightening, P = .001; bell clamp off, P < .001).
      During tightening of the bell clamp, significantly less crying was seen in the 5%
      lidocaine-prilocaine group (13 +/- 12 seconds) compared with 30% lidocaine (24 +/
      14 seconds) and controls (38 +/- 27 seconds) (P < .001). The group that received
      5% lidocaine-prilocaine also had no significant increase in systolic (t = 1.6, P
      = .12) or diastolic (t = 1.9, P = .067, respectively) blood pressure, unlike the
      group receiving 30% lidocaine (t = 4.8, P = .001 and t = 2.9, P = .009,
      respectively) and the placebo group (t = 2.5, P = .023 and t = 2.3, P = .032).
      There were no significant differences in oxygen saturation (alpha = .05, power
      0.79). CONCLUSION: Epicutaneous 5% lidocaine-prilocaine was more effective than
      30% lidocaine for neonatal circumcision, better reducing neonatal stress
      indicators. Lidocaine-prilocaine significantly shortened crying time during one
      of the most painful phases of circumcision. Both topical anesthetics were more
      effective than placebo in attenuating the behavioral and physiologic indicators
      of neonatal pain.

PMID- 10912986
TI  - Peritoneal fluid urea nitrogen and creatinine reference values.
AB  - OBJECTIVE: To evaluate urea nitrogen and creatinine levels in peritoneal fluid.
      METHODS: We prospectively evaluated 20 consecutive women having radical
      hysterectomy with lymphadenectomy. On postoperative days 2 and 3, serum, urine,
      and peritoneal fluid samples were tested for urea nitrogen and creatinine. Using
      power analysis we calculated an adequate sample size to be 16 patients. RESULTS:
      The mean urea nitrogen was 11 mg/dL in serum, 11 mg/dL in peritoneal fluid, and
      469 mg/dL in urine. The mean creatinine was .9 mg/dL in serum, 1.0 mg/dL in
      peritoneal fluid, and 141 mg/dL in urine. Urea nitrogen and creatinine values in
      peritoneal fluid and serum were essentially identical. Urine urea nitrogen and
      creatinine values were significantly greater than serum and peritoneal values (47
      to 157 times greater) (P < .011). On postoperative days 2 and 3, serial levels of
      serum, peritoneal fluid, and urine urea nitrogen and creatinine in the same
      subject showed no significant variation (P ranging from .19 to .31). CONCLUSION:
      Normal reference values of urea nitrogen and creatinine in peritoneal fluid are
      equivalent to serum values and significantly less than urine levels.

PMID- 10912987
TI  - A model for teaching newborn circumcision.
AB  - BACKGROUND: Hundreds of residents are trained to perform neonatal circumcision
      every year. This article describes the construction and use of a model designed
      to introduce trainees to neonatal circumcision using the Gomco technique.
      TECHNIQUE: A circumcision model was constructed using a clipboard, a pacifier,
      examination gloves, a rubber band, a syringe, tape, surgical towels, and a
      circumcision kit containing a 1.3 Gomco clamp, hemostats, surgical scissors, and
      a scalpel blade. DISCUSSION: With each trainee using a separate model, one
      instructor was able to guide four interns through three simulations each during a
      1-hour orientation session.

PMID- 10912988
TI  - Formal teaching of surgical skills in an obstetric-gynecologic residency.
AB  - OBJECTIVE: To describe a formal teaching program of basic surgical skills in an
      obstetric-gynecologic residency program and evaluate its effectiveness. METHODS:
      A surgical skills program was developed for all residents. Using bench and animal
      laboratory sessions, residents were given instruction and performed both
      laparoscopic and open abdominal procedures. All were given a pretest and were
      tested again 6 months later. Residents also evaluated their experiences. RESULTS:
      To date, the formal teaching sessions have been given to 24 residents, all of
      whom believed their confidence and technical skills improved as a result of the
      sessions. On a scale of 1 to 5, the median rating of the bench laboratory
      experience was 5 (range 4-5), and the pig laboratory was 5 (range 4-5). All
      residents believed the surgery sessions should be continued and the number of
      sessions increased. Preliminary evaluation indicated that time to suture a 10
      inch incision decreased by 28%, from an average of 225 (standard deviation [SD]
      51) seconds to 171 (SD 43) seconds (P < .001), and evaluation of surgical
      technique significantly improved at the second pretest (P = .013). Laparoscopic
      placement of pegs on a board in 2 minutes increased from an average of 5 (SD 2.5)
      to 7.3 (SD 2.6; P = .001). The cost of the bench laboratory sessions was minimal.
      Each pig was approximately $100, and the facility charge for each 4-hour
      laboratory session was $1500. CONCLUSION: When formal surgical training was given
      to obstetric-gynecologic residents, their surgical skills improved subjectively
      and objectively.

PMID- 10912989
TI  - Touch-pad technology: immediate feedback for resident educators in teenage
      reproductive health.
AB  - OBJECTIVE: To describe a program for residents in obstetrics and gynecology to
      design, research, and present an innovative teaching activity to secondary-school
      students in reproductive health. METHODS: An interactive 3-hour assembly was held
      for 285 grade-9 and -10 students. Six residents chose topics that encompassed key
      areas in adolescent health (menstruation, contraception, risk-taking behaviors,
      sexuality, and sexually transmitted diseases [STDs]). Each gave an interactive
      presentation designed to address issues identified through anonymous questions
      submitted by the students in advance. Touch-pad technology was used throughout
      the presentations to ascertain the students' knowledge about, and attitudes
      toward, a range of reproductive health issues. Each resident participant
      completed a follow-up questionnaire. RESULTS: Touch-pads provided a unique
      format, allowing teens to respond candidly to sensitive topics anonymously while
      providing important feedback to resident educators to help them focus their
      presentations and address areas of greatest need. Resident participants reported
      that by preparing these presentations, they honed their knowledge about
      contraception, STDs, and teen sexuality; identified important community resources
      for teens; and were sensitized to issues unique to teen sexual-health counseling.
      CONCLUSION: This project provided an opportunity for residents to improve their
      knowledge of teenage sexuality and to develop skills as teachers, while forging a
      valuable link between the community and the university.

PMID- 10912990
TI  - Risk factors for cesarean delivery in twin gestations near term.

PMID- 10912991
TI  - A blueprint for academic obstetrics and gynecology.

PMID- 10912992
TI  - Extracellular ATP-mediated propagation of Ca(2+) waves. Focus on "mechanical
      strain-induced Ca(2+) waves are propagated via ATP release and purinergic
      receptor activation".

PMID- 10912993
TI  - Focus on "molecular markers expressed in cultured and freshly isolated
      interstitial cells of Cajal".

PMID- 10912994
TI  - Reversible regulation of P2Y(2) nucleotide receptor expression in the duct
      ligated rat submandibular gland.
AB  - Ligation of the main excretory duct of the rat submandibular gland (SMG) produces
      a pronounced atrophy that is reversed upon ligature removal. Based on previous
      studies by our group and others suggesting that P2Y(2) nucleotide receptors are
      upregulated in response to tissue damage, we hypothesized that P2Y(2) receptor
      activity and mRNA levels would increase after duct ligation and return to control
      levels after ligature removal. Our results support this hypothesis. Intracellular
      Ca(2+) mobilization in response to the P2Y(2) receptor agonist UTP in SMG cells
      was increased significantly after ligation periods of 1.5 to 7 days, whereas no
      significant response was observed in the contralateral, nonligated gland. P2Y(2)
      receptor mRNA, as measured by semiquantitative RT-PCR, increased about 15-fold
      after 3 days of ligation. These increases reverted to control levels by 14 days
      after ligature removal. In situ hybridization revealed that the changes in P2Y(2)
      receptor mRNA abundance occurred mostly in acinar cells, which also were more
      adversely affected by ligation, including an increase in the appearance of
      apoptotic bodies. These findings support the idea that P2Y(2) receptor
      upregulation may be an important component of the response to injury in SMG and
      that recovery of normal physiological function may signal a decreased requirement
      for P2Y(2) receptors.

PMID- 10912995
TI  - Mechanical strain-induced Ca(2+) waves are propagated via ATP release and
      purinergic receptor activation.
AB  - Mechanical strain applied to prostate cancer cells induced an intracellular
      Ca(2+) (Ca(i)(2+)) wave spreading with a velocity of 15 microm/s. Ca(i)(2+) waves
      were not dependent on extracellular Ca(2+) and membrane potential because
      propagation was unaffected in high-K(+) and Ca(2+)-free solution. Waves did not
      depend on the cytoskeleton or gap junctions because cytochalasin B and
      nocodazole, which disrupt microfilaments and microtubules, respectively, and 1
      heptanol, which uncouples gap junctions, were without effects. Fluorescence
      recovery after photobleaching experiments revealed an absence of gap junctional
      coupling. Ca(i)(2+) waves were inhibited by the purinergic receptor antagonists
      basilen blue and suramin; by pretreatment with ATP, UTP, ADP, UDP, 2-methylthio
      ATP, and benzoylbenzoyl-ATP; after depletion of ATP by 2-deoxyglucose; and after
      ATP scavenging by apyrase. Waves were abolished by the anion channel inhibitors 5
      nitro-2-(3-phenylpropylamino)benzoic acid, tamoxifen, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid, niflumic acid, and gadolinium. ATP
      release following strain was significantly inhibited by anion channel blockers.
      Hence, ATP is secreted via mechanosensitive anion channels and activates
      purinergic receptors on the same cell or neighboring cells in an autocrine and
      paracrine manner, thus leading to Ca(i)(2+) wave propagation.

PMID- 10912997
TI  - Low extracellular Ca(2+) activates a transient Cl(-) current in chicken ovarian
      granulosa cells.
AB  - The effects of low Ca(2+) on ion currents in hen ovarian granulosa cells were
      examined. A fast activating and inactivating transient outward current (TOC) and
      a slowly activating outward current (SOC) could be observed. In the presence of
      normal Ca(2+) concentration (2. 5 mM) and with a holding potential of -80 mV, SOC
      was activated in all cells with command pulses more positive than -20 mV. In 2.5
      mM Ca(2+), TOC appeared in 10% of cells at the command pulse of +80 mV and in 60
      85% of cells at +100 to +120 mV. In low-Ca(2+) solution and command potential of
      +80 mV (holding potential of -80 mV), the amplitude of TOC was enhanced in cells
      that expressed it in normal Ca(2+), and TOC appeared in 43% of the cells that did
      not express it initially in normal Ca(2+). At both normal and low Ca(2+) levels,
      TOC decreased as the holding potential became more positive. TOC was reduced in
      Cl(-)-deficient solution and in the presence of 5-nitro-2-(3
      phenylpropylamino)benzoic acid, a Cl(-) channel blocker. These findings suggest
      that chicken granulosa cells express a Ca(2+)-inactivated TOC carried by Cl(-).
      This current may serve as a signal for some of the reduced metabolic functions of
      granulosa cells associated with Ca(2+) deficiency.

PMID- 10912996
TI  - Role of Rho in Ca(2+)-insensitive contraction and paxillin tyrosine
      phosphorylation in smooth muscle.
AB  - We investigated whether Rho activation is required for Ca(2+)-insensitive
      paxillin phosphorylation, myosin light chain (MLC) phosphorylation, and
      contraction in tracheal muscle. Tyrosine-phosphorylated proteins have been
      implicated in the Ca(2+)-insensitive contractile activation of smooth muscle
      tissues. The contractile activation of tracheal smooth muscle increases tyrosine
      phosphorylation of the cytoskeletal proteins paxillin and focal adhesion kinase.
      Paxillin is implicated in integrin-mediated signal transduction pathways that
      regulate cytoskeletal organization and cell motility. In fibroblasts and other
      nonmuscle cells, paxillin tyrosine phosphorylation depends on the activation of
      Rho and is inhibited by cytochalasin, an inhibitor of actin polymerization. In
      permeabilized muscle strips, we found that ACh induced Ca(2+)-insensitive
      contraction, MLC phosphorylation, and paxillin tyrosine phosphorylation. Ca(2+)
      insensitive contraction and MLC phosphorylation induced by ACh were inhibited by
      C3 transferase, an inhibitor of Rho activation; however, C3 transferase did not
      inhibit paxillin tyrosine phosphorylation. Ca(2+)-insensitive paxillin tyrosine
      phosphorylation was also not inhibited by the Rho kinase inhibitor Y-27632, by
      cytochalasin D, or by the inhibition of MLC phosphorylation. We conclude that, in
      tracheal smooth muscle, Rho mediates Ca(2+)-insensitive contraction and MLC
      phosphorylation but that Rho is not required for Ca(2+)-insensitive paxillin
      tyrosine phosphorylation. Paxillin phosphorylation also does not require
      actomyosin activation, nor is it inhibited by the actin filament capping agent
      cytochalasin D.

PMID- 10912998
TI  - Signaling mechanisms regulating bombesin-mediated AP-1 gene induction in the
      human gastric cancer SIIA.
AB  - The hormone bombesin (BBS) and its mammalian equivalent gastrin-releasing peptide
      (GRP) act through specific GRP receptors (GRP-R) to affect multiple cellular
      functions in the gastrointestinal tract; the intracellular signaling pathways
      leading to these effects are not clearly defined. Previously, we demonstrated
      that the human gastric cancer SIIA possesses GRP-R and that BBS stimulates
      activator protein-1 (AP-1) gene expression. The purpose of our present study was
      to determine the signaling pathways leading to AP-1 induction in SIIA cells. A
      rapid induction of c-jun and jun-B gene expression was noted after BBS treatment;
      this effect was blocked by specific GRP-R antagonists, indicating that BBS is
      acting through the GRP-R. The signaling pathways leading to increased AP-1 gene
      expression were delineated using phorbol 12-myristate 13-acetate (PMA), which
      stimulates protein kinase C (PKC)-dependent pathways, by forskolin (FSK), which
      stimulates protein kinase A (PKA)-dependent pathways, and by the use of various
      protein kinase inhibitors. Treatment with PMA stimulated AP-1 gene expression and
      DNA binding activity similar to the effects noted with BBS; FSK stimulated jun-B
      expression but produced only minimal increases of c-jun mRNA and AP-1 binding
      activity. Pretreatment of SIIA cells with either H-7 or H-8 (primarily PKC
      inhibitors) inhibited the induction of c-jun and jun-B mRNAs in response to BBS,
      whereas H-89 (PKA inhibitor) exhibited only minimal effects. Pretreatment with
      tyrphostin-25, a protein tyrosine kinase (PTK) inhibitor, attenuated the BBS
      mediated induction of c-jun and jun-B, but the effect was not as pronounced as
      with H-7. Collectively, our results demonstrate that BBS acts through its
      receptor to produce a rapid induction of both c-jun and jun-B mRNA and AP-1 DNA
      binding activity in the SIIA human gastric cancer. Moreover, this induction of AP
      1, in response to BBS, is mediated through both PKC- and PTK-dependent signal
      transduction pathways with only minimal involvement of PKA.

PMID- 10913000
TI  - Peroxynitrite-induced apoptosis involves activation of multiple caspases in HL-60
      cells.
AB  - In this study, we show that caspases 2, 3, 6, and 7 were activated during
      peroxynitrite-induced apoptosis in human leukemia HL-60 cells and that processing
      of these caspases was accompanied by cleavage of poly(ADP-ribose) polymerase and
      lamin B. Treatment of cells with DEVD-fluoromethyl ketone (FMK), a selective
      inhibitor for caspase 3-like proteases, resulted in a marked diminution of
      apoptotic cells. VAVAD-FMK, an inhibitor of caspase 2, partially inhibited the
      apoptotic response to peroxynitrite. However, selective inactivation of caspase 6
      by VEID-FMK did not affect apoptosis rates. These data suggest that caspase 3
      like proteases and caspase 2, but not caspase 6, are required for peroxynitrite
      induced apoptosis in this cell type. Moreover, we demonstrate that peroxynitrite
      treatment stimulated activation of caspases 8 and 9, two initial caspases in the
      apoptotic signaling pathway, and preincubation of cells with their inhibitor,
      IETD-FMK, inhibited activation of caspase 3-like proteases and caspase 2 at the
      concentration that prevents the apoptosis. These observations, together, suggest
      that caspase 8 and/or caspase 9 mediates activation of caspase 3-like proteases
      and caspase 2 during the apoptosis induced by peroxynitrite in HL-60 cells.

PMID- 10912999
TI  - Functional TSH receptor in human abdominal preadipocytes and orbital fibroblasts.
AB  - Controversy continues about whether, and to what levels of abundance, thyroid
      stimulating hormone receptors (TSHR) are found in human tissues other than the
      thyroid gland. Restricted expression to the thyroid and orbit would suggest that
      TSHR represents the target autoantigen in thyroid-associated ophthalmopathy. A
      more generalized pattern of tissue expression would be inconsistent with TSHR
      acting as the autoantigen that is solely responsible for selectively targeting
      the immune system to the orbit. We have detected TSHR mRNA in human abdominal
      adipose tissue by Northern blot analysis. TSHR protein was also detected, by
      immunoblotting with two different antibodies, in preadipocytes isolated from
      human abdominal subcutaneous and omental adipose tissue and in derivative
      adipocytes differentiated in primary culture. Preadipocytes treated with thyroid
      stimulating hormone (TSH) exhibited a sevenfold increase in the activity of p70
      S6 kinase, a serine/threonine kinase recently recognized as a downstream target
      of TSHR in thyroid cells. Activation of p70 S6 kinase by TSH was also observed in
      orbital fibroblasts. Thus TSHR protein expression is found in fibroblasts from
      several anatomic locations, suggesting that factors other than site-limited TSHR
      expression must be involved in restricting the distribution of Graves' disease
      manifestations. Furthermore, the presence of functional TSHR in preadipocytes
      raises the possibility of a novel role for TSHR signaling in adipose tissue
      development.

PMID- 10913001
TI  - Phosphatidylinositol 3-kinases regulate ERK and p38 MAP kinases in canine colonic
      smooth muscle.
AB  - In canine colon, M2/M3 muscarinic receptors are coupled to extracellular signal
      regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinases. We tested
      the hypothesis that this coupling is mediated by enzymes of the
      phosphatidylinositol (PI) 3-kinase family. RT-PCR and Western blotting
      demonstrated expression of two isoforms, PI 3-kinase-alpha and PI 3-kinase-gamma.
      Muscarinic stimulation of intact muscle strips (10 microM ACh) activated PI 3
      kinase-gamma, ERK and p38 MAP kinases, and MAP kinase-activated protein kinase-2,
      whereas PI 3-kinase-alpha activation was not detected. Wortmannin (25 microM)
      abolished the activation of PI 3-kinase-gamma, ERK, and p38 MAP kinases. MAP
      kinase inhibition was a PI 3-kinase-gamma-specific effect, since wortmannin did
      not inhibit recombinant activated murine ERK2 MAP kinase, protein kinase C, Raf
      1, or MAP kinase kinase. In cultured muscle cells, newborn calf serum (3%)
      activated PI 3-kinase-alpha and PI 3-kinase-gamma isoforms, ERK and p38 MAP
      kinases, and stimulated chemotactic cell migration. Using wortmannin and LY
      294002 to inhibit PI 3-kinase activity and PD-098059 and SB-203580 to inhibit ERK
      and p38 MAP kinases, we established that these enzymes are functionally important
      for regulation of chemotactic migration of colonic myocytes.

PMID- 10913002
TI  - Expression of GFRalpha-1, receptor for GDNF, in rat brain capillary during
      postnatal development of the BBB.
AB  - It is well known that the blood-brain barrier (BBB) matures at approximately 2 wk
      after birth in the rat. Recently, we showed that glial cell line-derived
      neurotrophic factor (GDNF) enhances the barrier function of porcine endothelial
      cells forming the BBB in culture. In the present study, we examined the relation
      between permeability of the BBB, using Evans blue as a tracer, and expression of
      the GDNF family receptor (GFRalpha-1) during postnatal development of the BBB.
      Morphometric analysis showed that exudation of Evans blue from capillaries of the
      cerebral cortex progressively decreased until postnatal day 21. Inversely,
      immunohistochemical examinations showed expression of GFRalpha-1 in the
      capillaries at postnatal day 3 and expression that reached the same levels as
      observed in adult rats by postnatal day 10. However, c-ret, which is thought to
      mediate a signal evoked by binding of GDNF to GFRalpha-1, was not expressed in
      the capillaries of the brain cortex in 3-mo-old rats. On the other hand, the
      tight junction proteins occludin and ZO-1 appeared to be fully expressed at
      birth. The reciprocal relation between GFRalpha-1 expression and the permeability
      of the BBB strongly suggests active participation of GDNF in postnatal
      development of the BBB, although the mechanism(s) involved is still veiled.

PMID- 10913003
TI  - Clathrin in mitotic spindles.
AB  - Subconfluent cultures of Madin-Darby canine kidney (MDCK) and CV-1 cells were
      immunostained with two monoclonal antibodies (MAbs), MAb X-22 and MAb 23, against
      clathrin heavy chain and with polyclonal antiserum against a conserved region of
      all mammalian clathrin light chains. In interphase MDCK and CV-1 cells, staining
      by all three antibodies resulted in the characteristic intracellular punctate
      vesicular and perinuclear staining pattern. In mitotic cells, all three anti
      clathrin antibodies strongly stained the mitotic spindle. Staining of clathrin in
      the mitotic spindle was colocalized with anti-tubulin staining of microtubular
      arrays in the spindle. Staining of the mitotic spindle was evident in mitotic
      cells from prometaphase to telophase and in spindles in mitotic cells released
      from a thymidine-nocodazole block. In CV-1 cells, staining of clathrin in the
      mitotic spindle was not affected by brefeldin A. On Western blots, clathrin was
      detected, but not enriched, in isolated spindles. The immunodetection of clathrin
      in the mitotic spindle may suggest a novel role for clathrin in mitosis.
      Alternatively, the recruitment of clathrin to the spindle may suggest a novel
      regulatory mechanism for localization of clathrin in mitotic cells.

PMID- 10913004
TI  - Forskolin-induced apical membrane insertion of virally expressed, epitope-tagged
      CFTR in polarized MDCK cells.
AB  - Channel gating of the cystic fibrosis transmembrane conductance regulator (CFTR)
      is activated in response to cAMP stimulation. In addition, CFTR activation may
      also involve rapid insertion of a subapical pool of CFTR into the plasma membrane
      (PM). However, this issue has been controversial, in part because of the
      difficulty in distinguishing cell surface vs. intracellular CFTR. Recently, a
      fully functional, epitope-tagged form of CFTR (M2-901/CFTR) that can be detected
      immunologically in nonpermeabilized cells was characterized (Howard M, Duvall MD,
      Devor DC, Dong J-Y, Henze K, and Frizzell RA. Am J Physiol Cell Physiol 269:
      C1565-C1576, 1995; and Schultz BD, Takahashi A, Liu C, Frizzell RA, and Howard M.
      Am J Physiol Cell Physiol 273: C2080-C2089, 1997). We have developed replication
      defective recombinant adenoviruses that express M2-901/CFTR and used them to
      probe cell surface CFTR in forskolin (FSK)-stimulated polarized Madin-Darby
      canine kidney (MDCK) cells. Virally expressed M2-901/CFTR was functional and was
      readily detected on the apical surface of FSK-stimulated polarized MDCK cells.
      Interestingly, at low multiplicity of infection, we observed FSK-stimulated
      insertion of M2901/CFTR into the apical PM, whereas at higher M2-901/CFTR
      expression levels, no increase in surface expression was detected using indirect
      immunofluorescence. Immunoelectron microscopy of unstimulated and FSK-stimulated
      cells confirmed the M2-901/CFTR redistribution to the PM upon FSK stimulation and
      demonstrates that the apically inserted M2-901/CFTR originates from a population
      of subapical vesicles. Our observations may reconcile previous conflicting
      reports regarding the effect of cAMP stimulation on CFTR trafficking.

PMID- 10913005
TI  - Genistein activates CFTR-mediated Cl(-) secretion in the murine trachea and
      colon.
AB  - The action of the isoflavone genistein on the cystic fibrosis transmembrane
      conductance regulator (CFTR) has been studied in many cell systems but not in
      intact murine tissues. We have investigated the action of genistein on murine
      tissues from normal and cystic fibrosis (CF) mice. Genistein increased the short
      circuit current (I(sc)) in tracheal (16.4 +/- 2.8 microA/cm(2)) and colonic (40.0
      +/- 4.4 microA/cm(2)) epithelia of wild-type mice. This increase was inhibited by
      furosemide, diphenylamine-2-carboxylate, and glibenclamide, but not by DIDS. In
      contrast, genistein produced no significant change in the I(sc) of the tracheal
      epithelium (0.9 +/- 1.1 microA/cm(2)) and decreased the I(sc) of colons from CF
      null (-13.1 +/- 2.3 microA/cm(2)) and DeltaF508 mice (-10.3 +/- 1.3
      microA/cm(2)). Delivery of a human CFTR cDNA-liposome complex to the airways of
      CF null mice restored the genistein response in the tracheas to wild-type levels.
      Tracheas from DeltaF508 mice were also studied: 46% of trachea showed no response
      to genistein, whereas 54% gave an increase in I(sc) similar to that in wild type.
      We conclude that genistein activates CFTR-mediated Cl(-) secretion in the murine
      trachea and distal colon.

PMID- 10913006
TI  - Physiological functions of the regulatory domains of the cardiac Na(+)/Ca(2+)
      exchanger NCX1.
AB  - Physiological functions of the intracellular regulatory domains of the
      Na(+)/Ca(2+) exchanger NCX1 were studied by examining Ca(2+) handling in CCL39
      cells expressing a low-affinity Ca(2+) regulatory site mutant (D447V/D498I), an
      exchanger inhibitory peptide (XIP) region mutant displaying no Na(+) inactivation
      (XIP-4YW), or a mutant lacking most of the central cytoplasmic loop (Delta246
      672). We found that D447V/D498I was unable to efficiently extrude Ca(2+) from the
      cytoplasm, particularly during a small rise in intracellular Ca(2+) concentration
      induced by the physiological agonist alpha-thrombin or thapsigargin. The same
      mutant took up Ca(2+) much less efficiently than the wild-type NCX1 in Na(+)-free
      medium when transfectants were not loaded with Na(+), although it appeared to
      take up Ca(2+) normally in transfectants preloaded with Na(+). XIP-4YW and, to a
      lesser extent, Delta246-672, but not NCX1 and D447V/D498I, markedly accelerated
      the loss of viability of Na(+)-loaded transfectants. Furthermore, XIP-4YW was not
      activated by phorbol ester, whereas XIP-4YW and D447V/D498I were resistant to
      inhibition by ATP depletion. The results suggest that these regulatory domains
      play important roles in the physiological and pathological Ca(2+) handling by
      NCX1, as well as in the regulation of NCX1 by protein kinase C or ATP depletion.

PMID- 10913007
TI  - Ca(2+)-dependent activation of c-jun NH(2)-terminal kinase in primary rabbit
      proximal tubule epithelial cells.
AB  - Previous work from this laboratory demonstrated that arachidonic acid activates c
      jun NH(2)-terminal kinase (JNK) through oxidative intermediates in a Ca(2+)
      independent manner (Cui X and Douglas JG. Arachidonic acid activates c-jun N
      terminal kinase through NADPH oxidase in rabbit proximal tubular epithelial
      cells. Proc Natl Acad Sci USA 94: 3771-3776, 1997.). We now report that JNK can
      also be activated via a Ca(2+)-dependent mechanism by agents that increase the
      cytosolic Ca(2+) concentration (Ca(2+) ionophore A(23187), Ca(2+)-ATPase
      inhibitor thapsigargin) or deplete intracellular Ca(2+) stores [intracellular
      Ca(2+) chelator 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA)
      AM]. The activation of JNK by BAPTA-AM occurs despite a decrease in cytosolic
      Ca(2+) concentration as detected by the indicator dye fura 2, but appears to be
      related to Ca(2+) metabolism, because modification of BAPTA with two methyl
      groups increases not only the chelation affinity for Ca(2+), but also the potency
      for JNK activation. BAPTA-AM stimulates Ca(2+) influx across the plasma membrane,
      and the resulting local Ca(2+) increases are probably involved in activation of
      JNK because Ca(2+) influx inhibitors (SKF-96365, nifedipine) and lowering of the
      free extracellular Ca(2+) concentration with EGTA reduce the BAPTA-induced JNK
      activation.

PMID- 10913008
TI  - Acid incubation causes exocytic insertion of NHE3 in OKP cells.
AB  - Incubation of opossum kidney clone P (OKP) cells in acid media (pH 6. 8) causes
      activation of Na(+)/H(+) exchanger 3 (NHE3) at 6, 12, and 24 h. OKP cell NHE3
      protein abundance was increased by 45% at 24 h of acid incubation but was
      unaffected at 3-12 h. By contrast, apical membrane NHE3, measured by surface
      biotinylation, increased approximately twofold at 6, 12, and 24 h, mirroring the
      increase in activity. Acid incubation caused a 76% increase in exocytic insertion
      of NHE3 into the apical membrane but had no effect on endocytic internalization
      at 6 h. Latrunculin B, an inhibitor of microfilament organization, inhibited the
      acid-induced increases in apical membrane NHE3, exocytic insertion of NHE3, and
      NHE3 activity at 6 h. These studies demonstrate two mechanisms for acid-induced
      increases in NHE3 activity. Beginning at 6 h, there is an increase in apical
      membrane NHE3 that is due to stimulated exocytic insertion and is required for
      increased NHE3 activity. At 24 h, there is an additional increase in total
      cellular NHE3.

PMID- 10913009
TI  - Characterization of outward K(+) currents in isolated smooth muscle cells from
      sheep urethra.
AB  - The perforated-patch technique was used to measure membrane currents in smooth
      muscle cells from sheep urethra. Depolarizing pulses evoked large transient
      outward currents and several components of sustained current. The transient
      current and a component of sustained current were blocked by iberiotoxin,
      penitrem A, and nifedipine but were unaffected by apamin or 4-aminopyridine,
      suggesting that they were mediated by large-conductance Ca(2+)-activated K(+)
      (BK) channels. When the BK current was blocked by exposure to penitrem A (100 nM)
      and Ca(2+)-free bath solution, there remained a voltage-sensitive K(+) current
      that was moderately sensitive to blockade with tetraethylammonium (TEA; half
      maximal effective dose = 3.0 +/- 0.8 mM) but not 4-aminopyridine. Penitrem A (100
      nM) increased the spike amplitude and plateau potential in slow waves evoked in
      single cells, whereas addition of TEA (10 mM) further increased the plateau
      potential and duration. In conclusion, both Ca(2+)-activated and voltage
      dependent K(+) currents were found in urethral myocytes. Both of these currents
      are capable of contributing to the slow wave in these cells, suggesting that they
      are likely to influence urethral tone under certain conditions.

PMID- 10913010
TI  - Aldosterone induces ras methylation in A6 epithelia.
AB  - Aldosterone increases Na(+) reabsorption by renal epithelial cells: the acute
      actions (<4 h) appear to be promoted by protein methylation. This paper describes
      the relationship between protein methylation and aldosterone's action and
      describes aldosterone-mediated targets for methylation in cultured renal cells
      (A6). Aldosterone increases protein methylation from 7.90 +/- 0.60 to 20.1 +/-
      0.80 methyl ester cpm/microg protein. Aldosterone stimulates protein methylation
      by increasing methyltransferase activity from 14.0 +/- 0.64 in aldosterone
      depleted cells to 31.8 +/- 2.60 methyl ester cpm/microg protein per hour in
      aldosterone-treated cells. Three known methyltransferase inhibitors reduce the
      aldosterone-induced increase in methyltransferase activity. One of these
      inhibitors, the isoprenyl-cysteine methyltransferase-specific inhibitor, S-trans,
      trans-farnesylthiosalicylic acid, completely blocks aldosterone-induced protein
      methylation and also aldosterone-induced short-circuit current. Aldosterone
      induces protein methylation in two molecular weight ranges: near 90 kDa and
      around 20 kDa. The lower molecular weight range is the weight of small G
      proteins, and aldosterone does increase both Ras protein 1.6-fold and Ras
      methylation almost 12-fold. Also, Ras antisense oligonucleotides reduce the
      activity of Na(+) channels by about fivefold. We conclude that 1) protein
      methylation is essential for aldosterone-induced increases in Na(+) transport; 2)
      one target for methylation is p21(ras); and 3) inhibition of Ras expression or
      Ras methylation inhibits Na(+) channel activity.

PMID- 10913011
TI  - Similarity of A(3)-adenosine and swelling-activated Cl(-) channels in
      nonpigmented ciliary epithelial cells.
AB  - Chloride release from nonpigmented ciliary epithelial (NPE) cells is a final step
      in forming aqueous humor, and adenosine stimulates Cl(-) transport by these
      cells. Whole cell patch clamping of cultured human NPE cells indicated that the
      A(3)-selective agonist 1-deoxy-1-(6-[([3-iodophenyl]methyl)amino]-9H-purin-9-yl)
      N-methyl-be ta-D-ribofuranuronamide (IB-MECA) stimulated currents (I(IB-MECA)) by
      approximately 90% at +80 mV. Partial replacement of external Cl(-) with aspartate
      reduced outward currents and shifted the reversal potential (V(rev)) from -23 +/-
      2 mV to -0.0 +/- 0.7 mV. Nitrate substitution had little effect. Perfusion with
      the Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB) and
      niflumic acid inhibited the currents. Partial Cl(-) replacement with aspartate
      and NO(3)(-), and perfusion with NPPB, had similar effects on the swelling
      activated whole cell currents (I(Swell)). Partial cyclamate substitution for
      external Cl(-) inhibited inward and outward currents of both I(IB-MECA) and
      I(Swell). Both sets of currents also showed outward rectification and
      inactivation at large depolarizing potentials. The results are consistent with
      the concept that A(3)-subtype adenosine agonists and swelling activate a common
      population of Cl(-) channels.

PMID- 10913012
TI  - Contrasting effects of NO and peroxynitrites on HSP70 expression and apoptosis in
      human monocytes.
AB  - The free radicals nitric oxide (.NO) and superoxide (O(2)(-).) react to form
      peroxynitrite (ONOO(-)), a highly toxic oxidant species. In this study we
      investigated the respective effects of NO and ONOO(-) in monocytes from healthy
      human donors. Purified monocytes were incubated for 6 or 16 h with a pure NO
      donor (S-nitroso-N-acetyl-DL-penicillamine, 0-2 mM), an.NO/ONOO(-) donor (3
      morpholinosydnonimine chlorhydrate, 0-2 mM) with and without superoxide dismutase
      (200 IU/ml), or pure ONOO(-). We provide evidence that 3-morpholinosydnonimine
      chlorhydrate alone represents a strong stress to human monocytes leading to a
      dose-dependent increase in heat shock protein-70 (HSP70) expression,
      mitochondrial membrane depolarization, and cell death by apoptosis and necrosis.
      These phenomena were abolished by superoxide dismutase, suggesting that ONOO(-),
      but not.NO, was responsible for the observed effects. This observation was
      further strengthened by the absence of a stress response in cells exposed to S
      nitroso-N-acetyl-DL-penicillamine. Conversely, exposure of cells to ONOO(-) alone
      also induced mitochondrial membrane depolarization and cell death by apoptosis
      and necrosis. Thus ONOO(-) formation may well explain the toxic effect generally
      attributed to.NO.

PMID- 10913014
TI  - Actin filament disruption inhibits L-type Ca(2+) channel current in cultured
      vascular smooth muscle cells.
AB  - To clarify interactions between the cytoskeleton and activity of L-type Ca(2+)
      (Ca(L)) channels in vascular smooth muscle (VSM) cells, we investigated the
      effect of disruption of actin filaments and microtubules on the L-type Ca(2+)
      current [I(Ba(L))] of cultured VSM cells (A7r5 cell line) using whole cell
      voltage clamp. The cells were exposed to each disrupter for 1 h and then examined
      electrophysiologically and morphologically. Results of immunostaining using anti
      alpha-actin and anti-alpha-tubulin antibodies showed that colchicine disrupted
      both actin filaments and microtubules, cytochalasin D disrupted only actin
      filaments, and nocodazole disrupted only microtubules. I(Ba(L)) was greatly
      reduced in cells that were exposed to colchicine or cytochalasin D but not to
      nocodazole. Colchicine even inhibited I(Ba(L)) by about 40% when the actin
      filaments were stabilized by phalloidin or when the cells were treated with
      phalloidin plus taxol to stabilize both cytoskeletal components. These results
      suggest that colchicine must also cause some inhibition of I(Ba(L)) due to
      another unknown mechanism, e.g., a direct block of Ca(L) channels. In summary,
      actin filament disruption of VSM cells inhibits Ca(L) channel activity, whereas
      disrupting the microtubules does not.

PMID- 10913013
TI  - Pharmacological modulation of ion transport across wild-type and DeltaF508 CFTR
      expressing human bronchial epithelia.
AB  - Forskolin, UTP, 1-ethyl-2-benzimidazolinone (1-EBIO), NS004, 8-methoxypsoralen
      (Methoxsalen; 8-MOP), and genistein were evaluated for their effects on ion
      transport across primary cultures of human bronchial epithelium (HBE) expressing
      wild-type (wt HBE) and DeltaF508 (DeltaF-HBE) cystic fibrosis transmembrane
      conductance regulator. In wt HBE, the baseline short-circuit current (I(sc))
      averaged 27.0 +/- 0.6 microA/cm(2) (n = 350). Amiloride reduced this I(sc) by
      13.5 +/- 0.5 microA/cm(2) (n = 317). In DeltaF-HBE, baseline I(sc) was 33.8 +/-
      1.2 microA/cm(2) (n = 200), and amiloride reduced this by 29.6 +/- 1.5
      microA/cm(2) (n = 116), demonstrating the characteristic hyperabsorption of Na(+)
      associated with cystic fibrosis (CF). In wt HBE, subsequent to amiloride,
      forskolin induced a sustained, bumetanide-sensitive I(sc) (DeltaI(sc) = 8.4 +/-
      0.8 microA/cm(2); n = 119). Addition of acetazolamide, 5-(N-ethyl-N-isopropyl)
      amiloride, and serosal 4, 4'-dinitrostilben-2,2'-disulfonic acid further reduced
      I(sc), suggesting forskolin also stimulates HCO(3)(-) secretion. This was
      confirmed by ion substitution studies. The forskolin-induced I(sc) was inhibited
      by 293B, Ba(2+), clofilium, and quinine, whereas charybdotoxin was without
      effect. In DeltaF-HBE the forskolin I(sc) response was reduced to 1.2 +/- 0.3
      microA/cm(2) (n = 30). In wt HBE, mucosal UTP induced a transient increase in
      I(sc) (Delta I(sc) = 15. 5 +/- 1.1 microA/cm(2); n = 44) followed by a sustained
      plateau, whereas in DeltaF-HBE the increase in I(sc) was reduced to 5.8 +/- 0. 7
      microA/cm(2) (n = 13). In wt HBE, 1-EBIO, NS004, 8-MOP, and genistein increased
      I(sc) by 11.6 +/- 0.9 (n = 20), 10.8 +/- 1.7 (n = 18), 10.0 +/- 1.6 (n = 5), and
      7.9 +/- 0.8 microA/cm(2) (n = 17), respectively. In DeltaF-HBE, 1-EBIO, NS004,
      and 8-MOP failed to stimulate Cl(-) secretion. However, addition of NS004
      subsequent to forskolin induced a sustained Cl(-) secretory response (2.1 +/- 0.3
      microA/cm(2), n = 21). In DeltaF-HBE, genistein alone stimulated Cl(-) secretion
      (2.5 +/- 0.5 microA/cm(2), n = 11). After incubation of DeltaF-HBE at 26 degrees
      C for 24 h, the responses to 1-EBIO, NS004, and genistein were all potentiated. 1
      EBIO and genistein increased Na(+) absorption across DeltaF-HBE, whereas NS004
      and 8-MOP had no effect. Finally, Ca(2+)-, but not cAMP-mediated agonists,
      stimulated K(+) secretion across both wt HBE and DeltaF-HBE in a glibenclamide
      dependent fashion. Our results demonstrate that pharmacological agents directed
      at both basolateral K(+) and apical Cl(-) conductances directly modulate Cl(-)
      secretion across HBE, indicating they may be useful in ameliorating the ion
      transport defect associated with CF.

PMID- 10913015
TI  - VCAM-1-induced inwardly rectifying K(+) current enhances Ca(2+) entry in human
      THP-1 monocytes.
AB  - Hyperpolarization in human leukemia THP-1 monocytes adherent to vascular cell
      adhesion molecule (VCAM)-1 is due to an induction of inwardly rectifying K(+)
      currents (I(ir)) (Colden-Stanfield M and Gallin EK, Am J Physiol Cell Physiol
      275: C267-C277, 1998). We determined whether the VCAM-1-induced hyperpolarization
      is sufficient to augment the increase in intracellular free calcium ([Ca(2+)](i))
      produced by Ca(2+) store depletion with thapsigargin (TG) and readdition of
      external CaCl(2) in fura 2-loaded THP-1 monocytes. Whereas there was a 2.1-fold
      increase in [Ca(2+)](i) in monocytes bound to glass for 5 h in response to TG and
      CaCl(2) addition, adherence to VCAM-1 produced a 5-fold increase in [Ca(2+)](i).
      Depolarization of monocytes adherent to VCAM-1 by I(ir) blockade or exposure to
      high [K(+)] abolished the enhancement of the peak [Ca(2+)](i) response. In
      monocytes bound to glass, hyperpolarization of the membrane potential with
      valinomycin, a K(+) ionophore, to the level of hyperpolarization seen in cells
      adherent to VCAM-1 produced similar changes in peak [Ca(2+)](i). Adherence of
      monocytes to E-selectin produced a similar peak [Ca(2+)](i) to cells bound to
      glass. Thus monocyte adherence to the physiological substrate VCAM-1 produces a
      hyperpolarization that is sufficient to enhance Ca(2+) entry and may impact
      Ca(2+)-dependent monocyte function.

PMID- 10913016
TI  - Hypertrophic effect of selective beta(1)-adrenoceptor stimulation on ventricular
      cardiomyocytes from adult rat.
AB  - We investigated whether selective beta(1)-adrenoceptor stimulation causes
      hypertrophic growth on isolated ventricular cardiomyocytes from adult rat. As
      parameters for the induction of hypertrophic growth, the increases of
      [(14)C]phenylalanine incorporation, protein and RNA mass, and cell size were
      determined. Isoproterenol (Iso, 10 microM) alone had no growth effect. In the
      presence of the beta(2)-adrenoceptor antagonist ICI-118551 (ICI, 10 microM), Iso
      caused an increase in [(14)C]phenylalanine incorporation, protein and RNA mass,
      cell volume, and cross-sectional area. We showed for phenylalanine incorporation
      that the growth effect of Iso+ICI could be antagonized by beta(1)-adrenoceptor
      blockade with atenolol (10 microM) or metoprolol (10 microM), indicating that it
      was caused by selective beta(1)-adrenoceptor stimulation. The growth response to
      Iso+ICI was accompanied by an increase in ornithine decarboxylase (ODC) activity
      and expression. Inhibition of ODC by the ODC antagonist difluoromethylornithine
      (1 mM) attenuated this hypertrophic response, indicating that ODC induction is
      causally involved. The growth response to Iso+ICI was found to be cAMP
      independent but was sensitive to genistein (100 microM) or rapamycin (0.1
      microM). The reaction was enhanced in the presence of pertussis toxin (10
      microM). We conclude that selective beta(1)-adrenoceptor stimulation causes
      hypertrophic growth of ventricular cardiomyocytes by a mechanism that is
      independent of cAMP but dependent on a tyrosine kinase and ODC.

PMID- 10913017
TI  - Negative feedback regulation of activated macrophages via Fas-mediated apoptosis.
AB  - Apoptosis is a critical event for eliminating activated macrophages. Here we show
      that Fas-mediated apoptosis may participate in the mechanism of negative feedback
      regulation of activated macrophages. Cytokine-activated macrophages released high
      levels of nitric oxide (NO) that induced apoptosis in macrophages themselves.
      This NO-induced macrophage apoptosis was inhibited by a Fas-Fc chimeric molecule
      that binds to Fas ligand (FasL) and prevents its interaction with endogenous cell
      surface Fas. High levels of NO stimulated the release of the soluble form of FasL
      that was inhibited by a matrix metalloproteinase inhibitor KB-8301. High levels
      of NO also upregulated the expression of Fas mRNA in macrophages. In addition,
      macrophages isolated from Fas-lacking mice were resistant to NO-induced
      apoptosis. Finally, inhibition of apoptosis by a caspase inhibitor augmented
      peroxide production from activated macrophages. These findings suggest that high
      levels of NO released from activated macrophages may promote the Fas-mediated
      macrophage apoptosis that may be a negative feedback mechanism for elimination
      and the downregulation of activated macrophages in the vessel wall.

PMID- 10913018
TI  - ATP activates DNA synthesis by acting on P2X receptors in human osteoblast-like
      MG-63 cells.
AB  - In human osteoblast-like MG-63 cells, extracellular ATP increased [(3)H]thymidine
      incorporation and cell proliferation and synergistically enhanced platelet
      derived growth factor- or insulin-like growth factor I-induced [(3)H]thymidine
      incorporation. ATP-induced [(3)H]thymidine incorporation was mimicked by the
      nonhydrolyzable ATP analogs adenosine 5'-O-(3-thiotriphosphate) and adenosine 5'
      adenylylimidodiphosphate and was inhibited by the P2 purinoceptor antagonist
      suramin, suggesting involvement of P2 purinoceptors. The P2Y receptor agonist UTP
      and UDP and a P2Y receptor antagonist reactive blue 2 did not affect
      [(3)H]thymidine incorporation, whereas the P2X receptor antagonist pyridoxal
      phosphate-6-azophenyl-2',4-disulfonic acid inhibited ATP-induced [(3)H]thymidine
      incorporation, suggesting that ATP-induced DNA synthesis was mediated by P2X
      receptors. RT-PCR analysis revealed that MG-63 cells expressed P2X(4), P2X(5),
      P2X(6), and P2X(7), but not P2X(1), P2X(2), and P2X(3), receptors. In fura 2
      loaded cells, not only ATP, but also UTP, increased intracellular Ca(2+)
      concentration, and inhibitors for several Ca(2+)-activated protein kinases had no
      effect on ATP-induced DNA synthesis, suggesting that an increase in intracellular
      Ca(2+) concentration is not indispensable for ATP-induced DNA synthesis. ATP
      increased mitogen-activated protein kinase activity in a Ca(2+)-independent
      manner and synergistically enhanced platelet-derived growth factor- or insulin
      like growth factor I-induced kinase activity. Furthermore, the mitogen-activated
      protein kinase kinase inhibitor PD-98059 totally abolished ATP-induced DNA
      synthesis. We conclude that ATP increases DNA synthesis and enhances the
      proliferative effects of growth factors through P2X receptors by activating a
      mitogen-activated protein kinase pathway.

PMID- 10913019
TI  - Soluble P-selectin moderates complement-dependent reperfusion injury of ischemic
      skeletal muscle.
AB  - P-selectin is an adhesion molecule expressed on activated endothelial and
      platelet surfaces. The function of the short consensus repeats (SCRs) of P
      selectin, homologous with the SCRs of complement regulatory proteins is largely
      unknown. In a model of murine hindlimb ischemia where local reperfusion injury is
      partly mediated by IgM natural antibody and classical complement pathway
      activation, we hypothesized that human soluble P-selectin (sP-sel) would moderate
      the complement component of the inflammatory response. Infusion of sP-sel
      supernatant or purified (p) sP-sel prepared from activated human platelets,
      reduced ischemic muscle vascular permeability by 48% and 43%, respectively,
      following reperfusion. Hindlimb immunohistochemistry demonstrated negligible C3
      staining colocalized with IgM in these groups compared with intense staining in
      the untreated injured mice. In vitro studies of mouse serum complement hemolytic
      activity showed that psP-sel inhibited the classical but not alternative
      complement pathway. Flow cytometry demonstrated that psP-sel inhibited C1q
      adherence to sensitized red blood cells. From these data we conclude that sP-sel
      moderates skeletal muscle reperfusion injury by inhibition of the classical
      complement pathway.

PMID- 10913020
TI  - Molecular markers expressed in cultured and freshly isolated interstitial cells
      of Cajal.
AB  - Located within the tunica muscularis of the gastrointestinal (GI) tract are
      networks of cells known as interstitial cells of Cajal (ICC). ICC are critical
      for important basic functions of GI motility such as generation and propagation
      of slow-wave pacemaker activity and reception of regulatory inputs from the
      enteric nervous system. We have developed a novel procedure to identify and
      isolate individual ICC from freshly dispersed cell preparations of the murine
      small intestine and gastric fundus and to determine differential transcriptional
      expression We have compared the expression profiles of pacemaker ICC isolated
      from the murine small intestine (IC-MY) and ICC involved in neurotransmission
      from the gastric fundus (IC-IM). We have also compared expression profiles
      between ICC and smooth muscle cells (SMC) and between freshly isolated ICC and
      cultured ICC. Cultured ICC express smooth muscle myosin, whereas freshly
      dispersed ICC do not. All cell types express muscarinic receptor types M(2) and
      M(3), neurokinin receptors NK(1) and NK(3), and inhibitory receptor VIP-1,
      whereas only cultured ICC and SMC express VIP-2. Both cultured and freshly
      dispersed IC-IM and IC-MY express the soluble form of stem cell factor, whereas
      SMC from the gastric fundus express only the membrane-bound form.

PMID- 10913021
TI  - Hyperinsulinemia compensates for infection-induced impairment in net hepatic
      glucose uptake during TPN.
AB  - In animals receiving total parenteral nutrition (TPN), infection impairs net
      hepatic glucose uptake (NHGU) by 40% and induces mild hyperinsulinemia. In the
      normal animal, the majority of the glucose taken up by the liver is diverted to
      lactate, but in the infected state, lactate release is curtailed. Because of the
      hyperinsulinemia and reduced NHGU, more glucose is utilized by peripheral
      tissues. Our aims were to determine the role of infection-induced
      hyperinsulinemia in 1) limiting the fall in NHGU and hepatic lactate release and
      2) increasing the proportion of glucose disposed of by peripheral tissues.
      Chronically catheterized dogs received TPN for 5 days via the inferior vena cava.
      On day 3, a fibrin clot with a nonlethal dose of E. coli was placed into the
      peritoneal cavity; sham dogs received a sterile clot. On day 5, somatostatin was
      infused to prevent endogenous pancreatic hormone secretion, and insulin and
      glucagon were replaced at rates matching incoming hormone concentrations observed
      previously in sham or infected dogs. The TPN-derived glucose infusion was
      adjusted to maintain a constant arterial plasma glucose level of approximately
      120 mg/dl. after a basal blood sampling period, the insulin infusion rate was
      either maintained constant (infected time control, Hi-Ins, n = 6; sham time
      control, Sham, n = 6) or decreased (infected + reduced insulin, Lo-Ins; n = 6)
      for 180 min to levels seen in noninfected dogs (from 23 +/- 2 to 12 +/- 1
      microU/ml). Reduction of insulin to noninfected levels decreased NHGU by 1.4 +/-
      0.5 mg x kg(-1) x min(-1) (P < 0.05) and nonhepatic glucose utilization by 4.8 +/
      0.8 mg x kg(-1) x min(-1) (P < 0.01). The fall in NHGU was caused by a decline
      in HGU (Delta-0.6 +/- 0.4 mg x kg(-1) x min(-1)) and a concomitant increase in
      hepatic glucose production (HGP, Delta0.8 +/- 0.5 mg x kg(-1) x min(-1)); net
      hepatic lactate release was not altered. Hyperinsulinemia that accompanies
      infection 1) primarily diverts glucose carbon to peripheral tissues, 2) limits
      the fall in NHGU by enhancing HGU and suppressing HGP, and 3) does not enhance
      hepatic lactate release, thus favoring hepatic glucose storage. Compensatory
      hyperinsulinemia plays a critical role in facilitating hepatic and peripheral
      glucose disposal during an infection.

PMID- 10913022
TI  - Synthesis rate of plasma albumin is a good indicator of liver albumin synthesis
      in sepsis.
AB  - Plasma albumin is well known to decrease in response to inflammation. The rate of
      albumin synthesis from both liver and plasma was measured in vivo by use of a
      large dose of L-[(2)H(3)-(14)C]valine in rats injected intravenously with live
      Escherichia coli and in pair-fed control rats during the acute-phase period (2
      days postinfection). The plasma albumin concentration was reduced by 50% in
      infected rats compared with pair-fed animals. Infection induced a fall in both
      liver albumin mRNA levels and albumin synthesis relative to total liver protein
      synthesis. However, absolute liver albumin synthesis rate (ASR) was not affected
      by infection. In plasma, albumin fractional synthesis rate was increased by 50%
      in infected animals compared with pair-fed animals. The albumin ASR estimated in
      the plasma was similar in the two groups. These results suggest that
      hypoalbuminemia is not due to reduced albumin synthesis during sepsis. Moreover,
      liver and plasma albumin ASR were similar. Therefore, albumin synthesis measured
      in the plasma is a good indicator of liver albumin synthesis.

PMID- 10913023
TI  - Thyroid status and response to endothelin-1 in rat arterial vessels.
AB  - We have previously reported that changes in thyroid status are associated with
      significant alterations in skeletal muscle blood flow during exercise and that
      changes in endothelium-dependent vasodilation may contribute to these blood flow
      abnormalities. The purpose of this study was to test the hypothesis that altered
      endothelium-dependent vasoconstriction is also associated with changes in thyroid
      status. To test this hypothesis, rats were rendered hypothyroid with
      propylthiouracil (Hypo, n = 14) or hyperthyroid with triiodothyronine (Hyper, n =
      14) over approximately 3 mo. Treatment efficacy was confirmed by altered (P <
      0.05) citrate synthase activity in several hindlimb skeletal muscles from Hypo
      and Hyper, compared with that in muscles from euthyroid rats (Eut, n = 12).
      Vascular rings were prepared from abdominal aortae, and responses to several
      vasoactive agents were determined in vitro. As found previously, maximal
      acetylcholine-induced vasorelaxation was modulated by thyroid status (Eut, 47 +/-
      9; Hypo, 28 +/- 6; Hyper, 68 +/- 5%; P < 0.05). Contractile responses of vascular
      rings with intact endothelium to the endothelium-derived constrictor endothelin-1
      (ET-1), however, were similar among groups across a range of ET-1 concentrations.
      In addition, maximal responses [Eut, 3.75 +/- 0.47; Hypo, 2.72 +/- 0.25; Hyper,
      3.22 +/- 0.42 g; not significant (NS)] and sensitivities (Eut, 8.12 +/- 0.09;
      Hypo, 8.10 +/- 0.06; Hyper, 8.28 +/- 0.09 -log M; NS) to ET-1 were similar among
      groups. If these findings from the conduit-type abdominal aorta extend into
      resistance vasculature, it appears that changes in endothelium-dependent
      vasoconstriction do not contribute to skeletal muscle blood flow abnormalities
      associated with thyroid disease states.

PMID- 10913024
TI  - Malonyl-CoA content and fatty acid oxidation in rat muscle and liver in vivo.
AB  - Malonyl-CoA acutely regulates fatty acid oxidation in liver in vivo by inhibiting
      carnitine palmitoyltransferase. Thus rapid increases in the concentration of
      malonyl-CoA, accompanied by decreases in long-chain fatty acyl carnitine (LCFA
      carnitine) and fatty acid oxidation have been observed in liver of fasted-refed
      rats. It is less clear that it plays a similar role in skeletal muscle. To
      examine this question, whole body respiratory quotients (RQ) and the
      concentrations of malonyl-CoA and LCFA-carnitine in muscle were determined in 48
      h-starved rats before and at various times after refeeding. RQ values were 0.82
      at baseline and increased to 0.93, 1. 0, 1.05, and 1.09 after 1, 3, 12, and 18 h
      of refeeding, respectively, suggesting inhibition of fat oxidation in all
      tissues. The increases in RQ at each time point correlated closely (r = 0.98)
      with increases (50-250%) in the concentration of malonyl-CoA in soleus and
      gastrocnemius muscles and decreases in plasma FFA and muscle LCFA-carnitine
      levels. Similar changes in malonyl-CoA and LCFA-carnitine were observed in liver.
      The increases in malonyl-CoA in muscle during refeeding were not associated with
      increases in the assayable activity of acetyl-CoA carboxylase (ACC) or decreases
      in the activity of malonyl-CoA decarboxylase (MCD). The results suggest that,
      during refeeding after a fast, decreases in fatty acid oxidation occur rapidly in
      muscle and are attributable both to decreases in plasma FFA and increases in the
      concentration of malonyl-CoA. They also suggest that the increase in malonyl-CoA
      in this situation is not due to changes in the assayable activity of either ACC
      or MCD or an increase in the cytosolic concentration of citrate.

PMID- 10913025
TI  - Association of phosphatidylinositol 3-kinase with the insulin receptor:
      compartmentation in rat liver.
AB  - Phosphatidylinositol 3-kinase (PI 3-kinase) plays an important role in a variety
      of hormone and growth factor-mediated intracellular signaling cascades and has
      been implicated in the regulation of a number of metabolic effects of insulin,
      including glucose transport and glycogen synthase activation. In the present
      study we have examined 1) the association of PI 3-kinase with the insulin
      receptor kinase (IRK) in rat liver and 2) the subcellular distribution of PI 3
      kinase-IRK interaction. Insulin treatment promoted a rapid and pronounced
      recruitment of PI 3-kinase to IRKs located at the plasma membrane, whereas no
      increase in association with endosomal IRKs was observed. In contrast to IRS-1
      associated PI 3-kinase activity, association of PI 3-kinase with the plasma
      membrane IRK did not augment the specific activity of the lipid kinase. With use
      of the selective PI 3-kinase inhibitor wortmannin, our data suggest that the cell
      surface IRK beta-subunit is not a substrate for the serine kinase activity of PI
      3-kinase. The functional significance for the insulin-stimulated selective
      recruitment of PI 3-kinase to cell surface IRKs remains to be elucidated.

PMID- 10913026
TI  - Pyruvate overrides inhibition of PDH during exercise after a low-carbohydrate
      diet.
AB  - The effects of carbohydrate deprivation on the regulation of pyruvate
      dehydrogenase (PDH) were studied at rest and during moderate-intensity exercise.
      An inhibitory effect of a chronic low-carbohydrate diet (LCD) on the active form
      of PDH (PDHa) mediated by a stable increase in PDH kinase (PDHK) activity has
      recently been reported (Peters SJ, Howlett RA, St. Amand TA, Heigenhauser GJF,
      and Spriet LL. Am J Physiol Endocrinol Metab 275: E980-E986, 1998.). In the
      present study, seven males cycled at 65% maximal O(2) uptake for 30 min after a 6
      day LCD. Exercise was repeated 1 wk later after a mixed diet (MD). Muscle
      biopsies were sampled from the vastus lateralis at rest and at 2 and 30 min of
      exercise. At rest, PDHa activity (0.18 +/- 0.04 vs. 0.63 +/- 0.18 mmol x min(-1)
      x kg wet wt(-1)), muscle glycogen content (310.2 +/- 36.9 vs. 563.9 +/- 32.6
      mmol/kg dry wt), and muscle lactate content (2.6 +/- 0.3 vs. 4.2 +/- 0.6 mmol/kg
      dry wt) were significantly lower after the LCD. Resting muscle acetyl-CoA (10.8
      +/- 1.9 vs. 7.4 +/- 0.8 micromol/kg dry wt) and acetylcarnitine (5.3 +/- 1.4 vs.
      1.6 +/- 0.3 mmol/kg dry wt) contents were significantly elevated after the LCD.
      During exercise, PDHa, glycogenolytic rate (LCD 5.8 +/- 0.4 vs. MD 6.9 +/- 0.2
      mmol x min(-1) x kg dry wt(-1)), and muscle concentrations of acetylcarnitine,
      pyruvate, and lactate increased to the same extent in both conditions. The
      results of the present study suggest that inhibition of resting PDH by elevated
      PDHK activity after a LCD may be overridden by the availability of muscle
      pyruvate during exercise.

PMID- 10913027
TI  - Importance of the hepatic arterial glucose level in generation of the portal
      signal in conscious dogs.
AB  - The aim of this study was to determine whether the elimination of the hepatic
      arterial-portal (A-P) venous glucose gradient would alter the effects of portal
      glucose delivery on hepatic or peripheral glucose uptake. Three groups of 42-h
      fasted conscious dogs (n = 7/group) were studied. After a 40-min basal period,
      somatostatin was infused peripherally along with intraportal insulin (7.2 pmol x
      kg(-1) x min(-1)) and glucagon (0.65 ng x kg(-1) x min(-1)). In test period 1 (90
      min), glucose was infused into a peripheral vein to double the hepatic glucose
      load (HGL) in all groups. In test period 2 (90 min) of the control group (CONT),
      saline was infused intraportally; in the other two groups, glucose was infused
      intraportally (22.2 micromol x kg(-1) x min(-1)). In the second group (PD),
      saline was simultaneously infused into the hepatic artery; in the third group
      (PD+HAD), glucose was infused into the hepatic artery to eliminate the negative
      hepatic A-P glucose gradient. HGL was twofold basal in each test period. Net
      hepatic glucose uptake (NHGU) was 10.1 +/- 2.2 and 12.8 +/- 2.1 vs. 11.5 +/- 1.6
      and 23.8 +/- 3.3* vs. 9.0 +/- 2.4 and 13.8 +/- 4.2 micromol x kg(-1) x min(-1) in
      the two periods of CONT, PD, and PD+HAD, respectively (* P < 0.05 vs. same test
      period in PD and PD+HAD). NHGU was 28.9 +/- 1.2 and 39.5 +/- 4.3 vs. 26.3 +/- 3.7
      and 24.5 +/- 3.7* vs. 36.1 +/- 3.8 and 53.3 +/- 8.5 micromol x kg(-1) x min(-1)
      in the first and second periods of CONT, PD, and PD+HAD, respectively (* P < 0.05
      vs. same test period in PD and PD+HAD). Thus the increment in NHGU and decrement
      in extrahepatic glucose uptake caused by the portal signal were significantly
      reduced by hepatic arterial glucose infusion. These results suggest that the
      hepatic arterial glucose level plays an important role in generation of the
      effect of portal glucose delivery on glucose uptake by liver and muscle.

PMID- 10913029
TI  - Amino acids regulate skeletal muscle PHAS-I and p70 S6-kinase phosphorylation
      independently of insulin.
AB  - Refeeding reverses the muscle protein loss seen with fasting. The physiological
      regulators and cellular control sites responsible for this reversal are
      incompletely defined. Phosphorylation of phosphorylated heat-acid stabled protein
      (PHAS-I) frees eukaryotic initiation factor 4E (eIF4E) and stimulates protein
      synthesis by accelerating translation initiation. Phosphorylation of p70 S6
      kinase (p70(S6k)) is thought to be involved in the regulation of the synthesis of
      some ribosomsal proteins and other selected proteins with polypyrimidine clusters
      near the transcription start site. We examined whether phosphorylation of PHAS-I
      and p70(S6k) was increased by feeding and determined the separate effects of
      insulin and amino acids on PHAS-I and p70(S6k) phosphorylation in rat skeletal
      muscle in vivo. Muscle was obtained from rats fed ad libitum or fasted overnight
      (n = 5 each). Other fasted rats were infused with insulin (3 microU x min(-1) x
      kg(-1), euglycemic clamp), amino acids, or the two combined. Gastrocnemius was
      freeze-clamped, and PHAS-I and p70(S6k) phosphorylation was measured by
      quantifying the several phosphorylated forms of these proteins seen on Western
      blots. We observed that feeding increased phosphorylation of both PHAS-I and
      p70(S6k) (P < 0.05). Infusion of amino acids alone reproduced the effect of
      feeding. Physiological hyperinsulinemia increased p70(S6K) (P < 0.05) but not
      PHAS-I phosphorylation (P = 0.98). Addition of insulin to amino acid infusion was
      no more effective than amino acids alone in promoting PHAS-I and p70(S6k)
      phosphorylation. We conclude that amino acid infusion alone enhances the
      activation of the protein synthetic pathways in vivo in rat skeletal muscle. This
      effect is not dependent on increases in plasma insulin and simulates the
      activation of protein synthesis that accompanies normal feeding.

PMID- 10913028
TI  - Effect of high-fat diet, surrounding temperature, and enterostatin on uncoupling
      protein gene expression.
AB  - Nonshivering thermogenesis induced in brown adipose tissue (BAT) during high-fat
      feeding is mediated through uncoupling protein 1 (UCP1). UCP2 is a recently
      identified homologue found in many tissues. To determine the role of UCP1 and
      UCP2 in thermoregulation and energy balance, we investigated the long-term effect
      of high-fat feeding on mRNA levels in mice at two different ambient temperatures.
      We also treated mice with the anorectic peptide enterostatin and compared mRNA
      levels in BAT, white adipose tissue (WAT), stomach, and duodenum. Here, we report
      that high-fat feeding at 23 degrees C increased UCP1 and UCP2 levels in BAT four-
      and threefold, respectively, and increased UCP2 levels fourfold in WAT. However,
      at 29 degrees C, UCP1 decreased, whereas UCP2 remained unchanged in BAT and
      increased twofold in WAT. Enterostatin increased UCP1 and decreased UCP2 mRNA in
      BAT. In stomach and duodenum, high-fat feeding decreased UCP2 mRNA, whereas
      enterostatin increased it. Our results suggest that the regulation of uncoupling
      protein mRNA levels by high-fat feeding is dependent on ambient temperature and
      that enterostatin is able to modulate it.

PMID- 10913030
TI  - Plasma leptin in moderately obese men: independent effects of weight loss and
      aerobic exercise.
AB  - The independent effects of weight loss and exercise on plasma leptin and total
      (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in
      52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control
      (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight
      loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma
      leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent
      weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5
      +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml).
      Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/-
      1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and
      SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue
      after weight loss results in a collateral decrease in circulating leptin, and
      exercise, independent of its effects on weight loss, has no profound influence on
      leptin secretion.

PMID- 10913031
TI  - Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis
      in brown fat.
AB  - To study the thermal response of interscapular brown fat (IBF) to norepinephrine
      (NE), urethan-anesthetized rats (1.2 g/kg ip) maintained at 28-30 degrees C
      received a constant venous infusion of NE (0-2 x 10(4) pmol/min) over a period of
      60 min. IBF temperatures (T(IBF)) were recorded with a small thermistor fixed
      under the IBF pad. Data were plotted against time and expressed as maximal
      variation (Deltat degrees C). Saline-injected rats showed a decrease in T(IBF) of
      approximately 0.6 degrees C. NE infusion increased T(IBF) by a maximum of
      approximately 3.0 degrees C at a dose of 10(4) pmol x min(-1) x 100 g body wt(
      1). Surgically thyroidectomized (Tx) rats kept on 0.05% methimazole showed a flat
      response to NE. Treatment with thyroxine (T(4), 0.8 microg x 100 g(-1) x day(-1))
      for 2-15 days normalized mitochondrial UCP1 (Western blotting) and IBF thermal
      response to NE, whereas iopanoic acid (5 mg x 100 g body wt(-1) x day(-1))
      blocked the effects of T(4). Treatment with 3,5, 3'-triiodothyronine (T(3), 0.6
      microg x 100 g body wt(-1) x day(-1)) for up to 15 days did not normalize UCP1
      levels. However, these animals showed a normal IBF thermal response to NE. Cold
      exposure for 5 days or feeding a cafeteria diet for 20 days increased UCP1 levels
      by approximately 3.5-fold. Nevertheless, the IBF thermal response was only
      greater than that of controls when maximal doses of NE (2 x 10(4) pmol/min and
      higher) were used. CONCLUSIONS: 1) hypothyroidism is associated with a blunted
      IBF thermal response to NE; 2) two- to fourfold changes in mitochondrial UCP1
      concentration are not necessarily translated into heat production during NE
      infusion.

PMID- 10913033
TI  - The relationship between creatine kinase kinetics and exercise intensity in human
      forearm is unchanged by age.
AB  - Using (31)P magnetic resonance spectroscopy, creatine kinase (CK) reaction
      kinetics was assessed in the forearm flexor digitorum profundus muscle of healthy
      young (n = 11, age 34.7 +/- 5 yr) and older (n = 20, age 73.5 +/- 8 yr) subjects
      at rest, intermittent exercise at 20% maximum voluntary contraction (MVC), and
      40% MVC. Exercise resulted in a significant increase in the average ratio of
      inorganic phosphate (P(i)) to phosphocreatine (PCr) from resting values of 0.073
      +/- 0.031 (young) and 0.082 +/- 0.037 (older) to 0. 268 +/- 0.140 (young, P <
      0.01) and 0.452 +/- 0.387 (older, P < 0. 01) at 40% MVC. At 40% MVC,
      intracellular pH decreased significantly, from resting values of 7.08 +/- 0.08
      (young) and 7.08 +/- 0.11 (older) to 6.84 +/- 0.19 (young, P < 0.05) and to 6.75
      +/- 0.25 (older, P < 0.05). Average values of the pseudo-first-order reaction
      rate k((PCr-->ATP)) at rest were 0.07 +/- 0.04 s(-1) in the young and 0.07 +/-
      0.03 s(-1) in the older group. At both exercise levels, the reaction rate
      constant increased compared with the resting value, but only the difference
      between the resting value and the 20% MVC value, which showed an 86% higher
      reaction rate constant in both groups, reached statistical significance (P <
      0.05). No difference in the reaction rate constant between the young and older
      groups was observed at either exercise level. As with k((PCr-->ATP)), the average
      phosphorus flux through the CK reaction increased during exercise at 20% MVC (P <
      0.05 in the older group) but decreased toward resting values at 40% MVC in both
      groups. The data in our study suggest that normal aging does not significantly
      affect the metabolic processes associated with the CK reaction.

PMID- 10913032
TI  - Growth hormone decreases muscle glutamine production and stimulates protein
      synthesis in hypercatabolic patients.
AB  - We determined the effects of 24-h recombinant human growth hormone (rhGH)
      infusion into a femoral artery on leg muscle protein kinetics, amino acid
      transport, and glutamine metabolism in eight adult hypercatabolic trauma
      patients. Metabolic pathways were assessed by leg arteriovenous catheterization
      and muscle biopsies with the use of stable amino acid isotopes. Muscle mRNA
      levels of selected enzymes were determined by competitive PCR. rhGH infusion
      significantly accelerated the inward transport rates of phenylalanine and leucine
      and protein synthesis, whereas the muscle protein degradation rate and cathepsin
      B and UbB polyubiquitin mRNA levels were not significantly modified by rhGH. rhGH
      infusion decreased the rate of glutamine de novo synthesis and glutamine
      precursor availability, total branched-chain amino acid catabolism, and
      nonprotein glutamate utilization. Thus net glutamine release from muscle into
      circulation significantly decreased after rhGH administration ( approximately
      50%), whereas glutamine synthetase mRNA levels increased after rhGH infusion,
      possibly to compensate for reduced glutamine precursor availability. We conclude
      that, after trauma, the anticatabolic action of rhGH is associated with a
      potentially harmful decrease in muscle glutamine production.

PMID- 10913034
TI  - Individual severity of dietary obesity in unselected Wistar rats: relationship
      with hyperphagia.
AB  - We investigated the relative importance of overeating, thermogenesis, and
      uncoupling protein (UCP) expression in determining the severity of obesity in
      male Wistar rats fed a highly palatable diet. After 2 wk of feeding, body weight
      did not differ significantly from controls (248 +/- 4 vs. 229 +/- 3 g; P > 0.3),
      but rectal temperature, brown adipose tissue (BAT) mass, UCP3 expression in
      gastrocnemius muscle, and UCP2 expression in white adipose tissue (WAT) were all
      elevated in diet-fed animals. In a further study, rats fed a palatable diet for 8
      wk exhibited higher energy intake and rectal temperature than controls. Dietary
      obese rats were divided into high (427-490 g; n = 8) and low (313-410 g; n = 10)
      weight gainers. The high gainers ate significantly more than the low gainers, and
      energy intake was positively correlated with weight gain (r(2) = 0.72, P < 0.01).
      UCP2 and UCP3 mRNA levels in gastrocnemius muscle were significantly increased
      above lean controls in all diet-fed animals, whereas UCPs in WAT and BAT did not
      differ significantly from controls. Whereas rats fed palatable food exhibited a
      thermogenic response, there was no significant difference in core temperature
      between high and low gain groups (37. 5 +/- 0.1 vs. 37.6 +/- 0.1 degrees C; P >
      0.5). We conclude that a higher energy intake is the critical factor determining
      susceptibility to dietary obesity in unselected Wistar rats.

PMID- 10913035
TI  - Effect of endurance training on lipid metabolism in women: a potential role for
      PPARalpha in the metabolic response to training.
AB  - Endurance training increases fatty acid oxidation (FAO) and skeletal muscle
      oxidative capacity. However, the source of the additional fat and the mechanisms
      for increasing FAO capacity in muscle are not clear. We measured whole body and
      regional lipolytic activity and whole body and plasma FAO in six lean women
      during 90 min of bicycling exercise (50% pretraining peak O(2) consumption)
      before and after 12 wk of endurance training. We also assessed skeletal muscle
      content of peroxisome proliferator-activated receptor-alpha (PPARalpha) and its
      target proteins that regulate FAO [medium-chain and very long chain acyl-CoA
      dehydrogenase (MCAD and VLCAD)]. Despite a 25% increase in whole body FAO during
      exercise after training (P < 0.05), training did not alter regional adipose
      tissue lipolysis (abdominal: 0.56 +/- 0.26 and 0.57 +/- 0.10 micromol x 100 g(-1)
      x min(-1); femoral: 0.13 +/- 0.07 and 0.09 +/- 0.02 micromol x 100 g(-1) x min(
      1)), whole body palmitate rate of appearance in plasma (168 +/- 18 and 150 +/- 25
      micromol/min), and plasma FAO (554 +/- 61 and 601 +/- 45 micromol/min). However,
      training doubled the levels of muscle PPARalpha, MCAD, and VLCAD. We conclude
      that training increases the use of nonplasma fatty acids and may enhance skeletal
      muscle oxidative capacity by PPARalpha regulation of gene expression.

PMID- 10913036
TI  - Differential regulation of leptin expression and function in A/J vs. C57BL/6J
      mice during diet-induced obesity.
AB  - Obesity-resistant (A/J) and obesity-prone (C57BL/6J) mice were weaned onto low
      fat (LF) or high-fat (HF) diets and studied after 2, 10, and 16 wk. Despite
      consuming the same amount of food, A/J mice on the HF diet deposited less carcass
      lipid and gained less weight than C57BL/6J mice over the course of the study.
      Leptin mRNA was increased in white adipose tissue (WAT) in both strains on the HF
      diet but to significantly higher levels in A/J compared with C57BL/6J mice.
      Uncoupling protein 1 (UCP1) and UCP2 mRNA were induced by the HF diet in brown
      adipose tissue (BAT) and WAT of A/J mice, respectively, but not in C57BL/6J mice.
      UCP1 mRNA was also significantly higher in retroperitoneal WAT of A/J compared
      with C57BL/6J mice. The ability of A/J mice to resist diet-induced obesity is
      associated with a strain-specific increase in leptin, UCP1, and UCP2 expression
      in adipose tissue. The findings indicate that the HF diet does not compromise
      leptin-dependent regulation of adipocyte gene expression in A/J mice and suggest
      that maintenance of leptin responsiveness confers resistance to diet-induced
      obesity.

PMID- 10913037
TI  - Weight stability masks sarcopenia in elderly men and women.
AB  - Skeletal muscle loss or sarcopenia in aging has been suggested in cross-sectional
      studies but has not been shown in elderly subjects using appropriate measurement
      techniques combined with a longitudinal study design. Longitudinal skeletal
      muscle mass changes after age 60 yr were investigated in independently living,
      healthy men (n = 24) and women (n = 54; mean age 73 yr) with a mean +/- SD follow
      up time of 4.7 +/- 2.3 yr. Measurements included regional skeletal muscle mass,
      four additional lean components (fat-free body mass, body cell mass, total body
      water, and bone mineral), and total body fat. Total appendicular skeletal muscle
      (TSM) mass decreased in men (-0.8 +/- 1.2 kg, P = 0.002), consisting of leg
      skeletal muscle (LSM) loss (-0.7 +/- 0.8 kg, P = 0.001) and a trend toward loss
      of arm skeletal muscle (ASM; -0.2 +/- 0.4 kg, P = 0.06). In women, TSM mass
      decreased (-0.4 +/- 1.2 kg, P = 0.006) and consisted of LSM loss (-0.3 +/- 0.8
      kg, P = 0.005) and a tendency for a loss of ASM (-0.1 +/- 0.6 kg, P = 0.20).
      Multiple regression modeling indicates greater rates of LSM loss in men. Body
      weight in men at follow-up did not change significantly (-0.5 +/- 3.0 kg, P =
      0.44) and fat mass increased (+1.2 +/- 2.4 kg, P = 0.03). Body weight and fat
      mass in women were nonsignificantly reduced (-0.8 +/- 3.9 kg, P = 0.15 and -0.8
      +/- 3.5 kg, P = 0.12). These observations suggest that sarcopenia is a
      progressive process, particularly in elderly men, and occurs even in healthy
      independently living older adults who may not manifest weight loss.

PMID- 10913038
TI  - Effect of training on insulin sensitivity of glucose uptake and lipolysis in
      human adipose tissue.
AB  - Training increases insulin sensitivity of both whole body and muscle in humans.
      To investigate whether training also increases insulin sensitivity of adipose
      tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight
      endurance-trained (T) and eight sedentary (S) young men [insulin infusion rates:
      10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(
      2)]. Glucose and glycerol concentrations were measured in arterial blood and also
      by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose
      tissue and in quadriceps femoris muscle (glucose only). Adipose tissue blood flow
      was measured by (133)Xe washout. In the basal state, adipose tissue blood flow
      tended to be higher in T compared with S subjects, and in both groups blood flow
      was constant during the clamp. The change from basal in arterial-interstitial
      glucose concentration difference was increased in T during the clamp but not in S
      subjects in both adipose tissue and muscle [adipose tissue: step I (n = 8), 0.48
      +/- 0.18 mM (T), 0.23 +/- 0.11 mM (S); step II (n = 8), 0.19 +/- 0.09 (T), -0.09
      +/- 0.24 (S); step III (n = 5), 0.47 +/- 0.24 (T), 0.06 +/- 0.28 (S); (T: P <
      0.001, S: P > 0.05); muscle: step I (n = 4), 1. 40 +/- 0.46 (T), 0.31 +/- 0.21
      (S); step II (n = 4), 1.14 +/- 0.54 (T), -0.08 +/- 0.14 (S); step III (n = 4),
      1.23 +/- 0.34 (T), 0.24 +/- 0.09 (S); (T: P < 0.01, S: P > 0.05)]. Interstitial
      glycerol concentration decreased faster in T than in S subjects [half-time: T, 44
      +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P < 0.05]. In conclusion, training
      enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and
      in skeletal muscle. Furthermore, interstitial glycerol data suggest that training
      also increases insulin sensitivity of lipolysis in subcutaneous adipose tissue.
      Insulin per se does not influence subcutaneous adipose tissue blood flow.

PMID- 10913039
TI  - The mineralocorticoid receptor mediates aldosterone-induced differentiation of
      T37i cells into brown adipocytes.
AB  - By use of targeted oncogenesis, a brown adipocyte cell line was derived from a
      hibernoma of a transgenic mouse carrying the proximal promoter of the human
      mineralocorticoid receptor (MR) linked to the SV40 large T antigen. T37i cells
      remain capable of differentiating into brown adipocytes upon insulin and
      triiodothyronine treatment as judged by their ability to express uncoupling
      protein 1 and maintain MR expression. Aldosterone treatment of undifferentiated
      cells induced accumulation of intracytoplasmic lipid droplets and mitochondria.
      This effect was accompanied by a significant and dose-dependent increase in
      intracellular triglyceride content (half-maximally effective dose 10(-9) M) and
      involved MR, because it was unaffected by RU-38486 treatment but was totally
      abolished in the presence of aldosterone antagonists (spironolactone, RU-26752).
      The expression of early adipogenic gene markers, such as lipoprotein lipase,
      peroxisome proliferator-activated receptor-gamma, and adipocyte-specific fatty
      acid binding protein 2, was enhanced by aldosterone, confirming activation of the
      differentiation process. We demonstrate that, in the T37i cell line, aldosterone
      participates in the very early induction of brown adipocyte differentiation. Our
      findings may have a broader biological significance and suggest that MR is not
      only implicated in maintaining electrolyte homeostasis but could also play a role
      in metabolism and energy balance.

PMID- 10913040
TI  - Enhanced intestinal synthesis of polyamines from proline in cortisol-treated
      piglets.
AB  - This study was conducted to determine a role for cortisol in regulating
      intestinal ornithine decarboxylase (ODC) activity and to identify the metabolic
      sources of ornithine for intestinal polyamine synthesis in suckling pigs. Thirty
      two 21-day-old suckling pigs were randomly assigned to one of four groups with
      eight animals each and received daily intramuscular injections of vehicle
      solution (sesame oil; control), hydrocortisone 21-acetate (HYD; 25 mg/kg body
      wt), RU-486 (10 mg/kg body wt, a potent blocker of glucocorticoid receptors), or
      HYD plus RU-486 for two consecutive days. At 29 days of age, pigs were killed for
      preparation of jejunal enterocytes. The cytosolic fraction was prepared for
      determining ODC activity. For metabolic studies, enterocytes were incubated for
      45 min at 37 degrees C in 2 ml of Krebs-bicarbonate buffer (pH 7.4) containing 1
      mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U-(14)C]glutamine, or 1 mM
      [U-(14)C]proline plus 1 mM glutamine. Cortisol administration increased
      intestinal ODC activity by 230%, polyamine (putrescine, spermidine, and spermine)
      synthesis from ornithine and proline by 75-180%, and intracellular polyamine
      concentrations by 45-83%. Polyamine synthesis from arginine was not detected in
      enterocytes of control pigs but was induced in cells of cortisol-treated pigs.
      There was no detectable synthesis of polyamines from glutamine in enterocytes of
      all groups of pigs. The stimulating effects of cortisol on intestinal ODC
      activity and polyamine synthesis were abolished by coadministration of RU-486.
      Our data indicate that an increase in plasma cortisol concentrations stimulates
      intestinal polyamine synthesis via a glucocorticoid receptor-mediated mechanism
      and that proline (an abundant amino acid in milk) is a major source of ornithine
      for intestinal polyamine synthesis in suckling neonates.

PMID- 10913041
TI  - Vanadate restores glucose 6-phosphate in diabetic rats: a mechanism to enhance
      glucose metabolism.
AB  - Vanadate mimics the metabolic actions of insulin. In diabetic rodents, vanadate
      also sensitizes peripheral tissues to insulin. We have analyzed whether this
      latter effect is brought about by a mechanism other than the known
      insulinomimetic actions of vanadium in vitro. We report that the levels of
      glucose 6-phosphate (G-6-P) in adipose, liver, and muscle of streptozotocin
      treated (STZ)-hyperglycemic rats are 77, 50, and 58% of those in healthy control
      rats, respectively. Normoglycemia was induced by vanadium or insulin therapy or
      by phlorizin. Vanadate fully restored G-6-P in all three insulin-responsive
      peripheral tissues. Insulin did not restore G-6-P in muscle, and phlorizin was
      ineffective in adipose and muscle. Incubation of diabetic adipose explants with
      glucose and vanadate in vitro increased lipogenic capacity three- to fourfold
      (half-maximally effective dose = 11 +/- 1 microM vanadate). Lipogenic capacity
      was elevated when a threshold level of approximately 7.5 +/- 0.3 nmol G-6-P/g
      tissue was reached. In summary, 1) chronic hyperglycemia largely reduces
      intracellular G-6-P in all three insulin-responsive tissues; 2) vanadate therapy
      restores this deficiency, but insulin therapy does not restore G-6-P in muscle
      tissue; 3) induction of normoglycemia per se (i.e., by phlorizin) restores G-6-P
      in liver only; and 4) glucose and vanadate together elevate G-6-P in adipose
      explants in vitro and significantly restore lipogenic capacity above the
      threshold of G-6-P level. We propose that hyperglycemia-associated decrease in
      peripheral G-6-P is a major factor responsible for peripheral resistance to
      insulin. The mechanism by which vanadate increases peripheral tissue capacity to
      metabolize glucose and to respond to the hormone involves elevation of this
      hexose phosphate metabolite and the cellular consequences of this elevated level
      of G-6-P.

PMID- 10913042
TI  - Short-term fasting abolishes the sex-related difference in GH and leptin
      secretion in humans.
AB  - We studied growth hormone (GH) and leptin secretion in eight male (age 29.3 +/-
      1.2 yr, body mass index 22.2 +/- 0.5 kg/m(2)) and seven female normal subjects
      (28.0 +/- 0.8 yr, 20.1 +/- 0.7 kg/m(2)) before and after 36 h of fasting. In the
      fed state, 8-h mean GH and leptin concentrations were higher in females (P < 0.05
      and P < 0. 0001, respectively). Fasting increased GH and decreased leptin in both
      sexes. There was significant interaction between gender and fasting (P < 0.05 for
      GH and P < 0.005 for leptin). Females showed a slighter increase in GH but a more
      marked decrease in leptin, so that there was no significant gender-related
      difference in GH and leptin after fasting. Fasting did not modify insulin-like
      growth factor (IGF) I, IGF binding protein (IGFBP)-3, acid-labile subunit, or GH
      binding protein; increased IGFBP-1 and free fatty acids (P < 0.0001) but
      decreased glucose (P < 0.001) and insulin levels (P < 0.05). In males, insulin
      levels were higher (P < 0.05) in the fed state and underwent deeper reduction
      after fasting (interaction P < 0.03). In conclusion, GH and leptin secretions are
      higher in women than in men in the fed but not in the fasting condition, which
      abolishes these gender-related differences in humans.

PMID- 10913043
TI  - Longitudinal changes in growth hormone secretory process irregularity assessed
      transpubertally in healthy boys.
AB  - Clarifying the time evolution, and underlying neuroendocrine regulation, of
      hormone secretion during puberty is of pivotal importance both physiologically
      and clinically. We sought to determine whether clinical growth and elevated
      growth hormone (GH) release in pubertal boys are associated with shifts in the
      irregularity of GH secretory patterns. We studied GH release in 23 healthy boys
      longitudinally at approximately 4-mo intervals over a 6-yr period throughout
      puberty, by repetitive blood sampling at 20-min intervals for 24 h on each study
      date. To quantify serial irregularity in the GH profiles, we utilized approximate
      entropy (ApEn), a scale- and model-independent quantification of the extent of
      sequential "randomness." Complementary statistical analyses establish that on a
      per-subject basis, serum GH concentration-time series show greatest secretory
      disorderliness (maximal ApEn) in prepuberty and mid-to-late puberty, followed by
      a steep decline in ApEn to maximal orderliness in postpubertal adolescence (P <
      0.0001, ANOVA). Pooling all subject comparisons, we observed a persistent
      positive correlation between ApEn and growth velocity (GrVel), Pearson r = 0.467
      (P < < 10(-10)). Moreover, in general, ApEn(GH) preceded GrVel evolution, with a
      time frame lead of 4-8 mo providing the most pronounced correlations between ApEn
      and GrVel. In the setting of low postpubertal growth, per-subject ApEn values
      fell to approximately one-half of maximal ApEn values and, on average, were in
      the 13th percentile from minimal (P < < 10(-10)) for fully mature boys. Thus, in
      a longitudinal transpubertal analysis, greater irregularity in GH secretion
      corresponds to greater linear growth in boys, which culminates in highly regular
      GH secretory dynamics after sexual maturity. In addition to clinical utility,
      there may be added experimental merit in knowing that GH dynamics typically
      predict accelerated linear growth in 4-8 mo.

PMID- 10913044
TI  - Loss of regulation of lipogenesis in the Zucker diabetic (ZDF) rat.
AB  - We present here a study on the role of leptin in the regulation of lipogenesis by
      examining the effect of dietary macronutrient composition on lipogenesis in the
      leptin receptor-defective Zucker diabetic fatty rat (ZDF) and its lean litter
      mate (ZL). Animals were pair fed two isocaloric diets differing in their fat-to
      carbohydrate ratio providing 10 and 30% energy as fat. Lipogenesis was measured
      in the rats using deuterated water and isotopomer analysis. From the deuterium
      incorporation into plasma palmitate, stearate, and oleate, we determined de novo
      synthesis of palmitate and synthesis of stearate by chain elongation and of
      oleate by desaturation. Because the macronutrient composition and the caloric
      density were controlled, changes in de novo lipogenesis under these dietary
      conditions represent adaptation to changes in the fat-to-carbohydrate ratio of
      the diet. De novo lipogenesis was normally suppressed in response to the high-fat
      diet in the ZL rat to maintain a relatively constant amount of lipids
      transported. The ZDF rat had a higher rate of lipogenesis, which was not
      suppressed by the high-fat diet. The results suggest an important hormonal role
      of leptin in the feedback regulation of lipogenesis.

PMID- 10913045
TI  - Impact of endotoxin on UCP homolog mRNA abundance, thermoregulation, and
      mitochondrial proton leak kinetics.
AB  - Linking tissue uncoupling protein (UCP) homolog abundance with functional
      metabolic outcomes and with expression of putative genetic regulators promises to
      better clarify UCP homolog physiological function. A murine endotoxemia model
      characterized by marked alterations in thermoregulation was employed to examine
      the association between heat production, UCP homolog expression, and
      mitochondrial proton leak ("uncoupling"). After intraperitoneal
      lipopolysaccharide (LPS, approximately 6 mg/kg) injection, colonic temperature
      (T(c)) in adult female C57BL6/J mice dropped to a nadir of approximately 30
      degrees C by 8 h, preceded by a four- to fivefold drop in liver UCP2 and
      UCP5/brain mitochondrial carrier protein 1 mRNA levels, with no change in their
      hindlimb skeletal muscle (SKM) expression. SKM UCP3 mRNA rose fivefold during
      development of hypothermia and was correlated with an LPS-induced increase in
      plasma free fatty acid concentration. UCP2 and UCP5 transcripts recovered about
      three- to sixfold in both tissues starting at 6-8 h, preceding a recovery of T(c)
      between 16 and 24 h. SKM UCP3 followed an opposite pattern. Such results are not
      consistent with an important influence of UCP3 in driving heat production but do
      not preclude a role for UCP2 or UCP5 in this process. The transcription
      coactivator PGC-1 displayed a transient LPS-evoked rise (threefold) or drop (two-
      to fivefold) in SKM and liver expression, respectively. No differences between
      control and LPS-treated mouse liver or SKM in vitro mitochondrial proton leak
      were evident at time points corresponding to large differences in UCP homolog
      expression.

PMID- 10913046
TI  - Meal fatty acid uptake in human adipose tissue: technical and experimental design
      issues.
AB  - The adipose tissue uptake of dietary fat has been studied using fatty acid
      radiotracers incorporated into a meal, followed by adipose tissue biopsies. A
      number of experimental design issues, including the use of isotopic tracers to
      measure meal fatty acid oxidation and plasma appearance of tracer, as well as the
      heterogeneity of adipose tissue fatty acid uptake, have been addressed. We
      examined these questions in a study of 24 volunteers (12 men and 12 women) who
      consumed a meal containing [(3)H]triolein and [(14)C]triolein. Slight differences
      in the purity of [(3)H]triolein vs. [(14)C]triolein were found, which could
      affect the apparent adipose tissue uptake of meal fatty acids. The adipose tissue
      triglyceride specific activity from bilateral biopsy sites agreed well, implying
      that a unilateral biopsy is satisfactory for measuring tracer uptake. Meal fatty
      acid oxidation measured using [(3)H]triolein and [(14)C]triolein was well
      correlated (r = 0.79, P < 0.0001). The peak tracer appearance in plasma
      chylomicrons occurred 1 h after the ingestion of a second, unlabeled meal. Our
      findings have implications for the experimental design of future meal fatty acid
      tracer/adipose tissue biopsy studies.

PMID- 10913047
TI  - Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans.
AB  - We tested for gender differences in dietary fatty acid metabolism in 12 nonobese
      men and 12 nonobese women using the meal fatty acid tracer/adipose tissue biopsy
      study design. In addition to determining body composition, measurements of
      regional adipose tissue lipoprotein lipase activity, blood flow, and fat cell
      size were performed to place the meal fatty acid kinetic studies in perspective.
      Twenty-four hours after ingesting the test meal, the concentration of meal fatty
      acids was greater (P < 0.05) in abdominal subcutaneous than in thigh adipose
      tissue in both men (0. 61 +/- 0.12 vs. 0.45 +/- 0.09 mg/g) and women (0.59 +/-
      0.10 vs. 0. 43 +/- 0.05) but was not different between men and women. A greater
      percentage of dietary fat was stored in subcutaneous adipose tissue in women than
      in men (38 +/- 3 vs. 24 +/- 3%, respectively, P < 0. 05), and a greater portion
      of meal fatty acid disposal was unaccounted for in men. Significant gender
      differences in regional adipose tissue blood flow after meal ingestion were
      noted; the differences were in the direction that could support greater nutrient
      storage in lower body fat in women.

PMID- 10913048
TI  - The direct effects of catecholamines on hepatic glucose production occur via
      alpha(1)- and beta(2)-receptors in the dog.
AB  - The role of alpha- and beta-adrenergic receptor subtypes in mediating the actions
      of catecholamines on hepatic glucose production (HGP) was determined in sixteen
      18-h-fasted conscious dogs maintained on a pancreatic clamp with basal insulin
      and glucagon. The experiment consisted of a 100-min equilibration, a 40-min
      basal, and two 90-min test periods in groups 1 and 2, plus a 60-min third test
      period in groups 3 and 4. In group 1 [alpha-blockade with norepinephrine (alpha
      blo+NE)], phentolamine (2 microg x kg(-1) x min(-1)) was infused portally during
      both test periods, and NE (50 ng x kg(-1) x min(-1)) was infused portally at the
      start of test period 2. In group 2, beta-blockade with epinephrine (beta
      blo+EPI), propranolol (1 microg x kg(-1) x min(-1)) was infused portally during
      both test periods, and EPI (8 ng x kg(-1) x min(-1)) was infused portally during
      test period 2. In group 3 (alpha(1)-blo+NE), prazosin (4 microg x kg(-1) x min(
      1)) was infused portally during all test periods, and NE (50 and 100 ng x kg(-1)
      x min(-1)) was infused portally during test periods 2 and 3, respectively. In
      group 4 (beta(2)-blo+EPI), butoxamine (40 microg x kg(-1) x min(-1)) was infused
      portally during all test periods, and EPI (8 and 40 ng x kg(-1) x min(-1)) was
      infused portally during test periods 2 and 3, respectively. In the presence of
      alpha- or alpha(1)-adrenergic blockade, a selective rise in hepatic sinusoidal NE
      failed to increase net hepatic glucose output (NHGO). In a previous study, the
      same rate of portal NE infusion had increased NHGO by 1.6 +/- 0.3 mg x kg(-1) x
      min(-1). In the presence of beta- or beta(2)-adrenergic blockade, the selective
      rise in hepatic sinusoidal EPI caused by EPI infusion at 8 ng x kg(-1) x min(-1)
      also failed to increase NHGO. In a previous study, the same rate of EPI infusion
      had increased NHGO by 1.6 +/- 0.4 mg x kg(-1) x min(-1). In conclusion, in the
      conscious dog, the direct effects of NE and EPI on HGP are predominantly mediated
      through alpha(1)- and beta(2)-adrenergic receptors, respectively.

PMID- 10913049
TI  - Where has secondary amyloid gone?

PMID- 10913050
TI  - What competence does a rheumatologist need?: an international perspective.
AB  - OBJECTIVES: To forecast, on the basis of the past and present position of
      rheumatologists in Europe, the competence needed in the future to secure and
      promote the specialty within the healthcare network. METHODS: Union Europeenne
      des Medecins Specialistes/European Board of Rheumatology (UEMS/EBR) questionnaire
      on (a) training centres in Europe, (b) rheumatologists' skills, (c) UEMS core
      curriculum. RESULTS: 173 training centres in rheumatology were identified.
      Reponses to the questionnaire showed both harmony and diversity in the practice
      of rheumatology. Harmony arises from the need to (a) have an extensive and
      profound knowledge of, and clinical experience with, all the causes of painful or
      disabled locomotor apparatus; (b) manage such disorders in the most cost
      effective way; and (c) promote "shared clinical decision making". The diversity
      seen both among and within the European countries is due to the different
      activities of rheumatologists. CONCLUSION: Rheumatological competence must be
      based on a common core, as described in the UEMS core curriculum, and on deeper
      and diverse clinical or scientific knowledge covering the entire field of the
      specialty, to secure its flexibility and resilience in the market place and to
      promote its scientific development.

PMID- 10913053
TI  - Carol-nachman prize for rheumatology

PMID- 10913051
TI  - Yttrium radiosynoviorthesis in the treatment of knee arthritis in rheumatoid
      arthritis: a systematic review.
AB  - OBJECTIVE: To consider the question: How strong is the evidence in favour of
      yttrium synovectomy in chronic knee arthritis in patients with rheumatoid
      arthritis in comparison with placebo and intra-articular steroid treatment?
      METHODS: A systematic review of the literature was performed using Medline and
      the Embase database. RESULTS: Initially, seven papers were identified, but only
      two met the inclusion criteria. Neither study showed evidence in favour of
      yttrium synovectomy. CONCLUSION: From the point of view of evidence based
      medicine it should be seriously questioned whether yttrium synovectomy deserves a
      place in clinical practice.

PMID- 10913054
TI  - Apoptosis and inflammation

PMID- 10913052
TI  - Development of a logically devised line drawing atlas for grading of knee
      osteoarthritis.
AB  - OBJECTIVES: To (a) develop an atlas of line drawings for the assessment and
      grading of narrowing and osteophyte (that is, changes of osteoarthritis) on knee
      radiographs, and (b) compare the performance of this atlas with that of the
      standard Osteoarthritis Research Society (OARS) photographic atlas of
      radiographs. METHODS: Normal joint space widths (grade 0) for the medial and
      lateral tibiofemoral and medial and lateral patellofemoral compartments were
      obtained from a previous community study. Grades 1-3 narrowing in each
      compartment was calculated separately for men and women, grade 3 being bone on
      bone, grades 1 and 2 being two thirds and one third the value of grade 0. Maximum
      osteophyte size (grade 3) for each of eight sites was determined from 715
      bilateral knee x ray films obtained in a knee osteoarthritis (OA) hospital
      clinic; grades 1-2 were calculated as two thirds and one third reductions in the
      area of grade 3. Drawings for narrowing and osteophyte were presented separately.
      50 sets of bilateral knee x ray radiographs (standing, extended anteroposterior;
      flexed skyline) showing a spectrum of OA grades were scored by three observers,
      twice using the OARS atlas and twice using the drawn atlas. RESULTS:
      Intraobserver and interobserver reproducibility was similar and generally good
      with both atlases, though varied according to site. All three observers preferred
      the line drawing atlas for ease and convenience of use. Higher scores for
      patellofemoral narrowing and lower scores for osteophyte, especially medial
      femoral osteophyte, were seen using the line drawing atlas, showing that the two
      atlases are not equivalent instruments. CONCLUSION: A logically derived line
      drawing atlas for grading of narrowing and osteophyte at the knee has been
      produced. The atlas showed comparable reproducibility with the OARS atlas, but
      was discordant in several aspects of grading. Such a system has several
      theoretical and practical advantages and should be considered for use in knee OA
      studies.

PMID- 10913056
TI  - Increased cellularity and expression of adhesion molecules in muscle biopsy
      specimens from patients with rheumatoid arthritis with clinical suspicion of
      vasculitis, but negative routine histology.
AB  - OBJECTIVE: Histological analysis of random quadriceps muscle biopsy specimens can
      be used to detect vasculitis in patients with rheumatoid arthritis (RA). This
      study aimed at determining the immunohistological features in patients with
      clinical suspicion of rheumatoid vasculitis, but without a transmural infiltrate
      or fibrinoid necrosis of the vessel wall on routine histology. METHODS: Three
      groups of patients with RA were studied: (a) without clinical signs of vasculitis
      (n=6); (b) with recent onset of extra-articular features and a clinical suspicion
      of vasculitis but normal routine histology (n=11); and (c) with recent onset of
      extra-articular features and vasculitis, histologically proved either in muscle
      or other biopsy specimens (n=14). A control group of patients with osteoarthritis
      was also included (n=5). Frozen sections from quadriceps muscle biopsy specimens
      were analysed with monoclonal antibodies to detect CD3, CD4, CD8, CD68, ICAM-1,
      VCAM-1, and HLA-DR. The slides were evaluated using a semiquantitative scoring
      system (0-4). RESULTS: The mean scores gradually increased from group 1 to 3,
      leading to significant differences between groups 1 and 2, but not between groups
      2 and 3 for most markers (p< 0.05). Thus the pathological changes were similar
      for the two groups with clinical signs of vasculitis, even when the conventional
      histological evaluation was negative. Higher immunohistological scores were
      associated with perivascular infiltrates on routine histology. CONCLUSION: The
      pathophysiological events leading to vasculitis are reflected by the changes in
      the quadriceps muscle biopsy specimens. The data indicate that the sensitivity of
      examination of muscle biopsy specimens for the diagnosis of rheumatoid vasculitis
      can be increased by the use of new criteria.

PMID- 10913057
TI  - Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and
      Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis
      and synovial proliferation.
AB  - OBJECTIVE: To investigate the involvement of Tie-1 and Tie-2, receptor tyrosine
      kinases required for angiogenesis, in synovial proliferation and angiogenesis of
      rheumatoid arthritis (RA). METHODS: Synovial tissues from 10 patients with RA and
      three control subjects were analysed by double immunohistochemistry and reverse
      transcriptase polymerase chain reaction (RT-PCR). RESULTS: Expression of Tie-1
      and Tie-2 was seen in all synovia, but predominantly in papillary projected
      portions. In synovial lining cells, Tie-2 was expressed mainly in the basal layer
      and frequently colocalised with vimentin and proliferating cell nuclear antigen
      (PCNA), whereas Tie-1 was also expressed in the superficial layer. In stromal
      cells, Tie-2 immunoreactivity was restricted to vimentin positive fibroblast-but
      not macrophage derived cells, whereas Tie-1 expression was not dependent on the
      phenotype. Tie receptors were also highly expressed in the endothelium and
      surrounding pericytes of capillaries scattered over the papillary proliferated
      synovium without notable difference in the expression of the two receptors.
      Furthermore, Tie positive vessels often overexpressed PCNA. In normal synovia,
      expression of Tie receptors was restricted to the capillary endothelium. RT-PCR
      confirmed the expression of Tie-1 and Tie-2 in RA synovial tissues and also in
      the cultured synoviocytes. CONCLUSION: The results suggest the possible
      involvement of overexpressed Tie-1 and Tie-2 in synovial lining and stromal cells
      in the pathophysiology of RA synovitis, probably through distinct mechanisms.
      Furthermore, expression of Tie receptors in actively growing vasculature may
      reflect the direct involvement of these receptors in angiogenesis and subsequent
      vascularisation.

PMID- 10913058
TI  - Effect of intensive exercise on patients with active rheumatoid arthritis: a
      randomised clinical trial.
AB  - OBJECTIVE: To investigate the effects of a dynamic, intensive exercise regimen on
      pain, disease activity, and physical functioning in active rheumatoid arthritis
      (RA). METHODS: 64 patients with RA with a mean age of 60 (13) years and mean
      disease duration of 8 (8) years, admitted to hospital because of active disease,
      were randomly assigned to an intensive exercise programme or to a conservative
      exercise programme during their period in hospital with a mean length of 30 (14)
      days. The intensive exercise programme consisted of knee and shoulder dynamic and
      isometric muscle strengthening exercises against resistance five times a week and
      conditioning bicycle training three times a week and was supplemental to the
      conservative exercise programme of range of motion and isometric exercises.
      Indices of disease activity, pain, muscle strength, and functional ability were
      assessed at 0, 3, 6, 12, and 24 weeks by a blinded observer. RESULTS: The medical
      treatment during the study was the same in both groups. Both groups improved in
      measures of disease activity, differences between groups were not statistically
      significant. The mean improvement in disease activity score at 24 weeks in the
      intensive and conservative exercise group was -1.4 (1. 5) and -0.7 (1.4),
      respectively. Measures of physical functioning improved significantly for
      patients in the intensive exercise group, and differences between groups were
      statistically significant for measures of muscle strength. CONCLUSION: A short
      term intensive exercise programme in active RA is more effective in improving
      muscle strength than a conservative exercise programme and does not have
      deleterious effects on disease activity.

PMID- 10913059
TI  - Familial aggregation of Behcet's disease in Turkey.
AB  - OBJECTIVE: Familial aggregation of Behcet's disease has been reported previously.
      The current study aimed at investigating the sibling recurrence risk ratio
      (lambda s) for Behcet's disease, which is of value in the estimation of the
      magnitude of genetic factors in the pathogenesis of Behcet's disease. METHODS:
      170 consecutive unrelated index cases (98 male, 72 female) were interviewed with
      a detailed questionnaire to ascertain their family trees and the manifestations
      of Behcet's disease in their relatives. Subsequently, the immediately older
      sibling, or if an older sibling was not available, the immediately younger
      sibling, was selected as the second sibling for the evaluation. These siblings
      were contacted by telephone, and all subjects with recurrent oral ulcers were
      invited for examination. RESULTS: 31 of the 170 index cases had 51 relatives
      fulfilling the International Study Group criteria. Among 166 second siblings,
      seven had Behcet's disease (six male, one female) and 22 siblings (eight male, 14
      female) with recurrent oral ulcers were identified. Sibling recurrence rate
      defined as the ratio of the risk of being affected among the siblings of patients
      and the risk of being affected in the general population- was found to be 4.2%,
      which gives a lambda s value for Behcet's disease of between 11.4 and 52.5 in
      Turkey. CONCLUSIONS: A high lambda s value supports a strong genetic background
      for Behcet's disease which will be helpful in designing genetic linkage studies.

PMID- 10913060
TI  - Polymorphism in the vitamin D receptor gene and bone mass in African-American and
      white mothers and children: a preliminary report.
AB  - OBJECTIVE: To evaluate the contribution of polymorphisms in the vitamin D
      receptor (VDR) gene to ethnic variations in bone mass in mother and children from
      different ethnic origins. METHODS: VDR genotypes and bone mass in 43 African
      American and white women, mean age 38.2 years, and 41 of their children were
      studied. All children had a whole body bone mass measurement at age 9, and 39 had
      follow up measurements at age 11, while all the mothers had a single measurement.
      DNA was extracted from peripheral blood samples, subjected to polymerase chain
      reactions using primers specific for the VDR gene, and the Bsm1 restriction
      fragment length polymorphism defined. RESULTS: There was a significant ethnic
      difference in the VDR genotype frequencies among the adults and the children. No
      African-American subjects had the genotype "BB". In contrast, there was a 25%
      frequency of the "BB" genotype in the white adults and 24% in the white children.
      After pooling the ethnic groups, the mean bone mass in the "bb" genotype was
      significantly higher than in the "BB" genotype among the mothers, but this was
      not found in the children at baseline. However, by age 11, those with the "Bb" or
      "bb" genotypes had a larger gain in bone mass than those with "BB". CONCLUSION:
      These data support the suggestion that the ethnic difference in VDR genotype
      frequencies, together with the association between the genotypes and bone mass,
      may help to explain the well known ethnic differences in bone mass. Further, our
      observations suggest that VDR polymorphism may have an effect on bone mass during
      puberty as peak bone mass is accumulated.

PMID- 10913061
TI  - Coffee consumption, rheumatoid factor, and the risk of rheumatoid arthritis.
AB  - BACKGROUND: Recent epidemiological studies have suggested that smoking is a risk
      factor for rheumatoid factor (RF) positive rheumatoid arthritis (RA). Being
      overweight, high serum cholesterol, and dietary factors have in some studies been
      found to be associated with the risk of RA. No attention, however, has been paid
      to coffee consumption as a risk determinant, though it is a shared covariate of
      the alleged risk factors. OBJECTIVES: This study aimed at examining coffee
      consumption for its associations with RF positivity and with the risk of RA.
      METHODS: Coffee consumption was studied, firstly, for its association with RF
      (sensitised sheep cell agglutination titre >/=128) in a cross sectional survey of
      6809 subjects with no clinical arthritis, and secondly, for its prediction of RA
      in a cohort of 18 981 men and women who had neither arthritis nor a history of it
      at the baseline examination in 1973-76. Up to late 1989, 126 subjects of the
      cohort study had developed RA, of whom, 89 were positive for RF by the time of
      diagnosis. RESULTS: In the cross sectional survey the number of cups of coffee
      drunk daily was directly proportional to the prevalence of RF positivity.
      Adjusted for age and sex this association was significant (p value for linear
      trend, 0.008), but after further adjustment for smoking the linear trend declined
      below significance (p=0.06). In the cohort study there was an association between
      coffee consumption and the risk of RF positive RA that was not due to age, sex,
      level of education, smoking, alcohol intake, body mass index, or serum
      cholesterol. After adjustment for these potential confounders the users of four
      or more cups a day still had a relative risk of 2.20 (95% confidence interval
      1.13 to 4.27) for developing RF positive RA compared with those drinking less.
      Coffee consumption did not predict the development of RF negative RA. CONCLUSION:
      Coffee consumption may be a risk factor for RA, possibly through mechanisms
      contributing to the production of RF. This hypothesis remains to be tested in
      further studies.

PMID- 10913062
TI  - Spontaneous and cytokine regulated c-fos gene expression in rheumatoid synovial
      cells: resistance to cytokine stimulation when the c-fos gene is overexpressed.
AB  - OBJECTIVE: To study the effect of cytokines on the transactivation of the c-fos
      gene in relation to the contribution of overexpression of c-fos/AP-1 in
      rheumatoid joint destruction. METHODS: The promoter region (-447 to +109) of the
      human c-fos gene was integrated upstream of the chloramphenicol acetyltransferase
      (CAT) reporter gene, and the effect of cytokines on the expression of the c-fos
      gene was studied in the rheumatoid synovial cells of early (3-4) or late (14-18)
      passages, in the presence or absence of cytokines, by the transient transfection
      assay. RESULTS: Expression of c-fos gene was enhanced by tumour necrosis factor
      alpha (TNF alpha) and interleukin 6 (IL6) in the synovial cells of early passage,
      whereas it was not enhanced in the synovial cells of late passage. The c-fos gene
      expression was also enhanced by 13-O-tetradecanoyl phorbol-13-acetate (TPA) in
      early passage but was somewhat suppressed in the late passage. It was found that
      the c-fos gene and c-Fos protein were both increased in the synovial cells of
      late passage. Similarly, c-fos gene expression was also not increased by TPA or
      cytokine stimulation in the stable c-fos transformants (fos-pH8) or H-ras
      transformed NIH3T3 cells (NIH H-ras cells) that constitutively expressed c-fos
      genes. CONCLUSIONS: Although TNF alpha and IL6 augmented c-fos gene expression of
      rheumatoid synovial cells, transactivation of c-fos gene became resistant against
      cytokine stimulation under prolonged expression of c-fos gene, which may impart a
      tumour-like characteristic to rheumatoid synovial cells.

PMID- 10913064
TI  - Healing of erosions in rheumatoid arthritis.
AB  - Reports on healing of erosions in rheumatoid arthritis are rare. However, it is
      expected that repair of erosions should be seen more often during the period of
      extensive use of disease modifying antirheumatic drugs, especially in patients
      who experience sustained remission. Two such cases are described.

PMID- 10913063
TI  - Early radiographic features in patients with anterior cruciate ligament rupture.
AB  - OBJECTIVE: To determine, in a preliminary cross sectional study of patients with
      anterior cruciate ligament (ACL) ruptured knees, which of the radiographic
      features-subchondral cortical plate thickness, trabecular sclerosis, and
      osteophytosis-appears before or in association with changes in joint space width
      (JSW) as a surrogate for articular cartilage thickness in patients with ruptured
      knees. METHODS: 19 patients (14 men), mean (95% CI) age 28.7 (23.6 to 33.8)
      years, had ACL rupture in one knee only, confirmed by arthroscopy. Anterior draw,
      Lachman's test, and pivot shift tests were performed and x5 posteroanterior
      macroradiographs of both knees in a standing semiflexed view were taken at a mean
      (95% CI) time from injury of 34. 3 (26.9 to 41.7) months. In each radiograph,
      computerised methods were used to measure minimum JSW and fractal signature
      analysis (FSA) to quantify the vertical and horizontal trabecular organisation,
      osteophyte area, and the subchondral cortical plate thickness, in the medial and
      lateral tibial compartments of all knees. RESULTS: Physical examination confirmed
      the presence of joint laxity in the injured knees. No statistical difference in
      either medial or lateral JSW and subchondral cortical plate thickness was
      detected between ACL ruptured and uninjured knees. FSA showed a significant
      decrease in fractal dimension for the horizontal trabeculae (size 0.42 mm) in the
      medial compartment of the ACL ruptured knees compared with the uninjured knees
      (p<0.01, multivariate analysis of variance). There was an inverse correlation (R 
      0.74) between the time since knee injury and the difference in FSA values for ACL
      ruptured and uninjured knees in medial compartment horizontal trabeculae (size
      0.4 mm). No significant changes were detected in the lateral compartment.
      Osteophytes were detected in the medial compartment of nine ACL injured knees.
      CONCLUSION: Compared with the uninjured knee, ACL rupture leads to thickening of
      subchondral horizontal trabeculae (decreased FSA) in the medial tibial
      compartment of all knees, reaching significance at about four years after injury.
      Osteophytes were present in the same compartment in 9/19 knees. No changes in JSW
      and subchondral cortical plate thickness were detected. Whether the bony changes
      detected in these ACL ruptured knees presage those of early osteoarthritis
      requires further study.

PMID- 10913065
TI  - Assessment of primary hip osteoarthritis: comparison of radiographic methods
      using colon radiographs.
AB  - OBJECTIVE: To compare the reliability of quantitative measurement of minimum hip
      joint space with a qualitative global assessment of radiological features for
      estimating the prevalence of primary osteoarthritis (OA) of the hip in colon
      radiographs. METHODS: All colon radiographs from patients aged 35 or older, taken
      at three different radiographic departments in Iceland during the years 1990-96,
      were examined. A total of 3002 hips in 638 men and 863 women were analysed.
      Intraobserver and interobserver reliability was assessed by measuring 147
      randomly selected radiographs (294 hips) twice by the same observer, and 87 and
      98 randomly selected radiographs (174 and 196 hips) by two additional independent
      observers. Minimum hip joint space was measured with a millimetre ruler, and
      global assessment of radiological features by a published atlas. RESULTS: With a
      minimum joint space of 2.5 mm or less as definition for OA, 212 hips were defined
      as having OA. When the global Kellgren and Lawrence assessment with grade 2
      (definite narrowing in the presence of definite osteophytes) or higher as
      definition for OA was used, 202 hips showed OA. However, only 166 hips were
      diagnosed as OA with both systems. With 2.0 or 3.0 mm minimum joint space as cut
      off point, the difference between the two methods increased. Both intrarater and
      interrater reliability was significantly higher with joint space measurement than
      with global assessment. CONCLUSIONS: Overall prevalence of radiological OA was
      similar with the two methods. However, the quantitative measurement of minimum
      hip joint space had a better within-observer and between-observer reliability
      than qualitative global assessment of radiographic features of hip OA. It is thus
      suggested that minimum joint space measurement is a preferable method in
      epidemiological studies of radiological hip OA.

PMID- 10913066
TI  - Incidence of RA in people with persistently raised RF.

PMID- 10913068
TI  - TrfA-dependent inner membrane-associated plasmid RK2 DNA synthesis and
      association of TrfA with membranes of different gram-negative hosts.
AB  - TrfA, the replication initiator protein of broad-host-range plasmid RK2, was
      tested for its ability to bind to the membrane of four different gram-negative
      hosts in addition to Escherichia coli: Pseudomonas aeruginosa, Pseudomonas
      putida, Salmonella enterica serovar Typhimurium, and Rhodobacter sphaeroides.
      Cells harboring TrfA-encoding plasmids were fractionated into soluble, inner
      membrane, and outer membrane fractions. The fractions were subjected to Western
      blotting, and the blots were probed with antibody to the TrfA proteins. TrfA was
      found to fractionate with the cell membranes of all species tested. When the two
      membrane fractions of these species were tested for their ability to synthesize
      plasmid DNA endogenously (i.e., without added template or enzymes), only the
      inner membrane fraction was capable of extensive synthesis that was inhibited by
      anti-TrfA antibody in a manner similar to that of the original host species, E.
      coli. In addition, although DNA synthesis did occur in the outer membrane
      fraction, it was much less extensive than that exhibited by the inner membrane
      fraction and only slightly affected by anti-TrfA antibody. Plasmid DNA
      synthesized by the inner membrane fraction of one representative species, P.
      aeruginosa, was characteristic of supercoil and intermediate forms of the
      plasmid. Extensive DNA synthesis was observed in the soluble fraction of another
      representative species, R. sphaeroides, but it was completely unaffected by anti
      TrfA antibody, suggesting that such synthesis was due to repair and/or
      nonspecific chain extension of plasmid DNA fragments.

PMID- 10913067
TI  - rpoS mutants in archival cultures of Salmonella enterica serovar typhimurium.
AB  - Long-term survival under limited growth conditions presents bacterial populations
      with unique environmental challenges. The existence of Salmonella enterica
      serovar Typhimurium cultures undisturbed in sealed nutrient agar stab vials for
      34 to 45 years offered a unique opportunity to examine genetic variability under
      natural conditions. We have initiated a study of genetic changes in these
      archival cultures. We chose to start with examination of the rpoS gene since,
      among gram-negative bacteria, many genes needed for survival are regulated by
      RpoS, the stationary-phase sigma factor. In each of 27 vials examined, cells had
      the rpoS start codon UUG instead of the expected AUG of Salmonella and
      Escherichia coli strains recorded in GenBank. Ten of the 27 had additional
      mutations in the rpoS gene compared with the X77752 wild-type strain currently
      recorded in GenBank. The rpoS mutations in the 10 strains included two deletions
      as well as point mutations that altered amino acid sequences substantially. Since
      these stored strains were derived from ancestral cells inoculated decades ago and
      remained undisturbed, it is assumed that the 10 rpoS mutations occurred during
      storage. Since the remaining 17 sequences were wild type (other than in the start
      codon), it is obvious that rpoS remained relatively stable during decades of
      sealed storage.

PMID- 10913069
TI  - Transcription of the nfrA-ywcH operon from Bacillus subtilis is specifically
      induced in response to heat.
AB  - The NfrA protein, an oxidoreductase from the soil bacterium Bacillus subtilis, is
      synthesized during the stationary phase and in response to heat. Analysis of
      promoter mutants revealed that the nfrA gene belongs to the class III heat shock
      genes in B. subtilis. An approximate 10-fold induction at both the
      transcriptional and the translational levels was found after thermal upshock.
      This induction resulted from enhanced synthesis of mRNA. Genetic and Northern
      blot analyses revealed that nfrA and the gene downstream of nfrA are transcribed
      as a bicistronic transcriptional unit. The unstable full-length transcript is
      processed into two short transcripts encoding nfrA and ywcH. The nfrA-ywcH operon
      is not induced by salt stress or by ethanol. According to previously published
      data, the transcription of class III genes in general is activated in response to
      the addition of these stressors. However, this conclusion is based on experiments
      which lacked a valid control. Therefore, it seems possible that the transcription
      of all class III genes is specifically induced by heat shock.

PMID- 10913070
TI  - Identification and characterization of a membrane permease involved in iron
      hydroxamate transport in Staphylococcus aureus.
AB  - Staphylococcus aureus was shown to transport iron complexed to a variety of
      hydroxamate type siderophores, including ferrichrome, aerobactin, and
      desferrioxamine. An S. aureus mutant defective in the ability to transport ferric
      hydroxamate complexes was isolated from a Tn917-LTV1 transposon insertion library
      after selection on iron-limited media containing aerobactin and streptonigrin.
      Chromosomal DNA flanking the Tn917-LTV1 insertion was identified by sequencing of
      chromosomal DNA isolated from the mutant. This information localized the
      transposon insertion to a gene whose predicted product shares significant
      similarity with FhuG of Bacillus subtilis. DNA sequence information was then used
      to clone a larger fragment of DNA surrounding the fhuG gene, and this resulted in
      the identification of an operon of three genes, fhuCBG, all of which show
      significant similarities to ferric hydroxamate uptake (fhu) genes in B. subtilis.
      FhuB and FhuG are highly hydrophobic, suggesting that they are embedded within
      the cytoplasmic membrane, while FhuC shares significant homology with ATP-binding
      proteins. Given this, the S. aureus FhuCBG proteins were predicted to be part of
      a binding protein-dependent transport system for ferric hydroxamates. Exogenous
      iron levels were shown to regulate ferric hydroxamate uptake in S. aureus. This
      regulation is attributable to Fur in S. aureus because a strain containing an
      insertionally inactivated fur gene showed maximal levels of ferric hydroxamate
      uptake even when the cells were grown under iron-replete conditions. By using the
      Fur titration assay, it was shown that the Fur box sequences upstream of fhuCBG
      are recognized by the Escherichia coli Fur protein.

PMID- 10913071
TI  - Functional characterization of the HasA(PF) hemophore and its truncated and
      chimeric variants: determination of a region involved in binding to the hemophore
      receptor.
AB  - Hemophores are secreted by several gram-negative bacteria (Serratia marcescens,
      Pseudomonas aeruginosa, Pseudomonas fluorescens, and Yersinia pestis) and form a
      family of homologous proteins. Unlike the S. marcescens hemophore (HasA(SM)), the
      P. fluorescens hemophore HasA(PF) has an additional region of 12 residues located
      immediately upstream from the C-terminal secretion signal. We show that HasA(PF)
      undergoes a C-terminal cleavage which removes the last 21 residues when secreted
      from P. fluorescens and that only the processed form is able to deliver heme to
      the S. marcescens outer membrane hemophore-specific receptor, HasR(SM).
      Functional analysis of variants including those with an internal deletion of the
      extra C-terminal domain show that the secretion signal does not inhibit the
      biological activity, whereas the 12-amino-acid region located upstream does. This
      extra domain may inhibit the interaction of the hemophore with HasR(SM). To
      localize the hemophore regions involved in binding to HasR, chimeric HasA(PF)
      HasA(SM) proteins were tested for biological activity. We show that residues 153
      to 180 of HasA(PF) are necessary for its interaction with the receptor.

PMID- 10913072
TI  - Tissue-specific gene expression identifies a gene in the lysogenic phage Gifsy-1
      that affects Salmonella enterica serovar typhimurium survival in Peyer's patches.
AB  - In vivo expression technology was used to identify Salmonella enterica serovar
      Typhimurium genes that are transcriptionally induced when the bacteria colonize
      the small intestines of mice. These genes were subsequently screened for those
      that are transcriptionally inactive during the systemic stages of disease. This
      procedure identified gipA, a gene that is specifically induced in the small
      intestine of the animal. The gipA gene is carried on the lambdoid phage Gifsy-1.
      Consistent with the expression profile, the sole defect conferred by a gipA null
      mutation is in growth or survival in a Peyer's patch. The gipA strain is wild
      type in its ability to initially colonize the small intestine and invade the
      intestinal epithelium. The mutant also survives and propagates at wild-type
      levels during the systemic stages of disease. The gipA open reading frame is
      homologous to a family of putative insertion sequence elements, although our
      evidence shows that transposition is not required for gipA function in the
      Peyer's patch. These results suggest that the bacteria sense and respond to the
      particular environment of the Peyer's patch, a critical site for the replication
      of Salmonella serovar Typhimurium.

PMID- 10913074
TI  - The chromosomal location of the Bacillus subtilis sporulation gene spoIIR is
      important for its function.
AB  - Formation of the asymmetrically located septum during sporulation of Bacillus
      subtilis results in enclosure of the origin-proximal 30% of the chromosome in the
      prespore compartment. The rest of the chromosome is then translocated into the
      prespore from the mother cell. Transcription of spoIIR is initiated in the
      prespore by RNA polymerase containing sigma(F) soon after the septum is formed.
      The SpoIIR protein is required for the activation of the transcription program
      directed by sigma(E) in the mother cell. The spoIIR locus is located at 324
      degrees, near the origin of replication (0/360 degrees ). We show here that
      movement of spoIIR to 28 degrees had little effect on sporulation. However,
      movement to regions not in the origin-proximal part of the chromosome
      substantially reduced sporulation efficiency. At 283 degrees sporulation was
      reduced to less than 20% of the level obtained when spoIIR was at its natural
      location, and movement to 190 degrees reduced sporulation to about 6% of that
      level. These positional effects were also seen in the transcription of a spoIIR
      lacZ fusion. In contrast, movement of other spo-lacZ fusions from 28 degrees to
      190 degrees had little effect on their expression. These results suggest that
      spoIIR is the subject of "positional regulation," in the sense that the
      chromosomal position of spoIIR is important for its expression and function.

PMID- 10913073
TI  - Characterization of LrpC DNA-binding properties and regulation of Bacillus
      subtilis lrpC gene expression.
AB  - The lrpC gene was identified during the Bacillus subtilis genome sequencing
      project. Previous experiments suggested that LrpC has a role in sporulation and
      in the regulation of amino acid metabolism and that it shares features with
      Escherichia coli Lrp, a transcription regulator (C. Beloin, S. Ayora, R. Exley,
      L. Hirschbein, N. Ogasawara, Y. Kasahara, J. C. Alonso, and F. Le Hegarat, Mol.
      Gen. Genet. 256:63-71, 1997). To characterize the interactions of LrpC with DNA,
      the protein was overproduced and purified. We show that LrpC binds to multiple
      sites in the upstream region of its own gene with a stronger affinity for a
      region encompassing P1, one of the putative promoters identified (P1 and P2). By
      analyzing lrpC-lacZ transcriptional fusions, we demonstrated that P1 is the major
      in vivo promoter and that, unlike many members of the lrp/asnC family, lrpC is
      not negatively autoregulated but rather slightly positively autoregulated.
      Production of LrpC in vivo is low in both rich and minimal media (50 to 300 LrpC
      molecules per cell). In rich medium, the cellular LrpC content is six- to
      sevenfold lower during the exponentional phase than during the stationary growth
      phase. Possible determinants and the biological significance of the regulation of
      lrpC expression are discussed.

PMID- 10913075
TI  - Effect of altered spacing between uhpT promoter elements on transcription
      activation.
AB  - Many bacterial promoters possess multiple sites for binding of transcriptional
      activator proteins. The uhpT promoter, which controls expression of the sugar
      phosphate transport system in Escherichia coli, possesses multiple sites for its
      specific activator protein, UhpA, and a single site for binding of the global
      regulator, the catabolite gene activator protein (CAP). The binding of UhpA to
      the uhpT promoter was determined by DNase protection assays; UhpA displayed
      different affinities for the target sites. The upstream or strong sites, between
      positions -80 and -50, exhibited a higher affinity for UhpA than did the
      downstream or weak sites, between positions -50 and -32, adjoining the RNA
      polymerase-binding site. Phosphorylation of UhpA strongly increased its affinity
      for both sites. To examine the possible roles of the two sets of UhpA-binding
      sites, a series of insertion and deletion mutations were introduced at the
      boundary between them, as suggested from the positions that were protected by
      UhpA against hydroxyl radical cleavage. Deletions extended in the direction of
      the weak sites. The insertion or deletion of one helical turn of DNA resulted in
      the loss of promoter activity and of occupancy by UhpA of the remaining weak-site
      sequences but was accompanied by normal occupancy of the strong site and no
      change in the gel retardation behavior of the promoter fragments. However, the
      deletion of two helical turns of DNA, i.e., 20, 21, or 22 bp, resulted in the
      novel appearance of UhpA-independent expression and in an additional level of
      expression that was dependent on UhpA but independent of an inducing signal. The
      UhpA-independent promoter activity was shown to result from activation by CAP at
      its more proximal position. UhpA-dependent activity under noninducing conditions
      appears to result from the binding of unphosphorylated UhpA to the strong sites,
      which are now in the position normally occupied by the weak sites. Thus,
      regulated phosphorylation of the response regulator UhpA enhances its occupancy
      of the weak sites where favorable contacts can allow the binding of RNA
      polymerase to the promoter.

PMID- 10913076
TI  - Substrate specificity and signal transduction pathways in the glucose-specific
      enzyme II (EII(Glc)) component of the Escherichia coli phosphotransferase system.
AB  - Escherichia coli adapted to glucose-limited chemostats contained mutations in
      ptsG resulting in V12G, V12F, and G13C substitutions in glucose-specific enzyme
      II (EII(Glc)) and resulting in increased transport of glucose and methyl-alpha
      glucoside. The mutations also resulted in faster growth on mannose and
      glucosamine in a PtsG-dependent manner. By use of enhanced growth on glucosamine
      for selection, four further sites were identified where substitutions caused
      broadened substrate specificity (G176D, A288V, G320S, and P384R). The altered
      amino acids include residues previously identified as changing the uptake of
      ribose, fructose, and mannitol. The mutations belonged to two classes. First, at
      two sites, changes affected transmembrane residues (A288V and G320S), probably
      altering sugar selectivity directly. More remarkably, the five other specificity
      mutations affected residues unlikely to be in transmembrane segments and were
      additionally associated with increased ptsG transcription in the absence of
      glucose. Increased expression of wild-type EII(Glc) was not by itself sufficient
      for growth with other sugars. A model is proposed in which the protein
      conformation determining sugar accessibility is linked to transcriptional signal
      transduction in EII(Glc). The conformation of EII(Glc) elicited by either glucose
      transport in the wild-type protein or permanently altered conformation in the
      second category of mutants results in altered signal transduction and interaction
      with a regulator, probably Mlc, controlling the transcription of pts genes.

PMID- 10913077
TI  - Glucose transporter mutants of Escherichia coli K-12 with changes in substrate
      recognition of IICB(Glc) and induction behavior of the ptsG gene.
AB  - In Escherichia coli K-12, the major glucose transporter with a central role in
      carbon catabolite repression and in inducer exclusion is the phosphoenolpyruvate
      dependent glucose:phosphotransferase system (PTS). Its membrane-bound subunit,
      IICB(Glc), is encoded by the gene ptsG; its soluble domain, IIA(Glc), is encoded
      by crr, which is a member of the pts operon. The system is inducible by D-glucose
      and, to a lesser degree, by L-sorbose. The regulation of ptsG transcription was
      analyzed by testing the induction of IICB(Glc) transporter activity and of a
      single-copy Phi(ptsGop-lacZ) fusion. Among mutations found to affect directly
      ptsG expression were those altering the activity of adenylate cyclase (cyaA), the
      repressor DgsA (dgsA; also called Mlc), the general PTS proteins enzyme I (ptsI)
      and histidine carrier protein HPr (ptsH), and the IIA(Glc) and IIB(Glc) domains,
      as well as several authentic and newly isolated UmgC mutations. The latter,
      originally thought to map in the repressor gene umgC outside the ptsG locus, were
      found to represent ptsG alleles. These affected invariably the substrate
      specificity of the IICB(Glc) domain, thus allowing efficient transport and
      phosphorylation of substrates normally transported very poorly or not at all by
      this PTS. Simultaneously, all of these substrates became inducers for ptsG. From
      the analysis of the mutants, from cis-trans dominance tests, and from the
      identification of the amino acid residues mutated in the UmgC mutants, a new
      regulatory mechanism involved in ptsG induction is postulated. According to this
      model, the phosphorylation state of IIB(Glc) modulates IIC(Glc) which, directly
      or indirectly, controls the repressor DgsA and hence ptsG expression. By the same
      mechanism, glucose uptake and phosphorylation also control the expression of the
      pts operon and probably of all operons controlled by the repressor DgsA.

PMID- 10913078
TI  - Identification of the Pseudomonas aeruginosa glmM gene, encoding
      phosphoglucosamine mutase.
AB  - A search for a potential algC homologue within the Pseudomonas aeruginosa PAO1
      genome database has revealed an open reading frame (ORF) of unknown function,
      ORF540 in contig 54 (July 1999 Pseudomonas genome release), that theoretically
      coded for a 445-amino-acid-residue polypeptide (I. M. Tavares, J. H. Leitao, A.
      M. Fialho, and I. Sa-Correia, Res. Microbiol. 150:105-116, 1999). The product of
      this gene is here identified as the phosphoglucosamine mutase (GlmM) which
      catalyzes the conversion of glucosamine-6-phosphate to glucosamine-1-phosphate,
      an essential step in the formation of the cell wall precursor UDP-N
      acetylglucosamine. The P. aeruginosa gene has been cloned into expression vectors
      and shown to restore normal peptidoglycan biosynthesis and cell growth of a glmM
      Escherichia coli mutant strain. The GlmM enzyme from P. aeruginosa has been
      overproduced to high levels and purified to homogeneity in a six-histidine-tagged
      form. Beside its phosphoglucosamine mutase activity, the P. aeruginosa enzyme is
      shown to exhibit phosphomannomutase and phosphoglucomutase activities, which
      represent about 20 and 2% of its GlmM activity, respectively.

PMID- 10913079
TI  - Global gene expression profiles of Bacillus subtilis grown under anaerobic
      conditions.
AB  - Bacillus subtilis can grow under anaerobic conditions, either with nitrate or
      nitrite as the electron acceptor or by fermentation. A DNA microarray containing
      4,020 genes from this organism was constructed to explore anaerobic gene
      expression patterns on a genomic scale. When mRNA levels of aerobic and anaerobic
      cultures during exponential growth were compared, several hundred genes were
      observed to be induced or repressed under anaerobic conditions. These genes are
      involved in a variety of cell functions, including carbon metabolism, electron
      transport, iron uptake, antibiotic production, and stress response. Among the
      highly induced genes are not only those responsible for nitrate respiration and
      fermentation but also those of unknown function. Certain groups of genes were
      specifically regulated during anaerobic growth on nitrite, while others were
      primarily affected during fermentative growth, indicating a complex regulatory
      circuitry of anaerobic metabolism.

PMID- 10913081
TI  - Phosphate starvation-inducible proteins of Bacillus subtilis: proteomics and
      transcriptional analysis.
AB  - The phosphate starvation response in Bacillus subtilis was analyzed using two
      dimensional (2D) polyacrylamide gel electrophoresis of cell extracts and
      supernatants from phosphate-starved cells. Most of the phosphate starvation
      induced proteins are under the control of sigma(B), the activity of which is
      increased by energy depletion. In order to define the proteins belonging to the
      Pho regulon, which is regulated by the two-component regulatory proteins PhoP and
      PhoR, the 2D protein pattern of the wild type was compared with those of a sigB
      mutant and a phoR mutant. By matrix-assisted laser desorption ionization-time of
      flight mass spectrometry, two alkaline phosphatases (APases) (PhoA and PhoB), an
      APase-alkaline phosphodiesterase (PhoD), a glycerophosphoryl diester
      phosphodiesterase (GlpQ), and the lipoprotein YdhF were identified as very
      strongly induced PhoPR-dependent proteins secreted into the extracellular medium.
      In the cytoplasmic fraction, PstB1, PstB2, and TuaD were identified as already
      known PhoPR-dependent proteins, in addition to PhoB, PhoD, and the previously
      described PstS. Transcriptional studies of glpQ and ydhF confirmed the strong
      PhoPR dependence. Northern hybridization and primer extension experiments showed
      that glpQ is transcribed monocistronically from a sigma(A) promoter which is
      overlapped by four putative TT(A/T)ACA-like PhoP binding sites. Furthermore, ydhF
      might be cotranscribed with phoB initiating from the phoB promoter. Only a small
      group of proteins remained phosphate starvation inducible in both phoR and sigB
      mutant and did not form a unique regulation group. Among these, YfhM and YjbC
      were controlled by sigma(B)-dependent and unknown PhoPR-independent mechanisms.
      Furthermore, YtxH and YvyD seemed to be induced after phosphate starvation in the
      wild type in a sigma(B)-dependent manner and in the sigB mutant probably via
      sigma(H). YxiE was induced by phosphate starvation independently of sigma(B) and
      PhoPR.

PMID- 10913082
TI  - Structural analysis of Bacillus subtilis spore peptidoglycan during sporulation.
AB  - A major structural element of bacterial endospores is a peptidoglycan (PG) wall.
      This wall is produced between the two opposed membranes surrounding the
      developing forespore and is composed of two layers. The inner layer is the germ
      cell wall, which appears to have a structure similar to that of the vegetative
      cell wall and which serves as the initial cell wall following spore germination.
      The outer layer, the cortex, has a modified structure, is required for
      maintenance of spore dehydration, and is degraded during spore germination.
      Theories suggest that the spore PG may also play a mechanical role in the
      attainment of spore dehydration. Inherent in one of these models is the
      production of a gradient of cross-linking across the span of the spore PG. We
      report analyses of the structure of PG found within immature, developing Bacillus
      subtilis forespores. The germ cell wall PG is synthesized first, followed by the
      cortex PG. The germ cell wall is relatively highly cross-linked. The degree of PG
      cross-linking drops rapidly during synthesis of the first layers of cortex PG and
      then increases two- to eightfold across the span of the outer 70% of the cortex.
      Analyses of forespore PG synthesis in mutant strains reveal that some strains
      that lack this gradient of cross-linking are able to achieve normal spore core
      dehydration. We conclude that spore PG with cross-linking within a broad range is
      able to maintain, and possibly to participate in, spore core dehydration. Our
      data indicate that the degree of spore PG cross-linking may have a more direct
      impact on the rate of spore germination and outgrowth.

PMID- 10913080
TI  - The serotype of type Ia and III group B streptococci is determined by the
      polymerase gene within the polycistronic capsule operon.
AB  - Streptococcus agalactiae is a primary cause of neonatal morbidity and mortality.
      Essential to the virulence of this pathogen is the production of a type-specific
      capsular polysaccharide (CPS) that enables the bacteria to evade host immune
      defenses. The identification, cloning, sequencing, and functional
      characterization of seven genes involved in type III capsule production have been
      previously reported. Here, we describe the cloning and sequencing of nine
      additional adjacent genes, cps(III)FGHIJKL, neu(III)B, and neu(III)C. Sequence
      comparisons suggested that these genes are involved in sialic acid synthesis,
      pentasaccharide repeating unit formation, and oligosaccharide transport and
      polymerization. The type III CPS (cpsIII) locus was comprised of 16 genes within
      15.5 kb of contiguous chromosomal DNA. Primer extension analysis and
      investigation of mRNA from mutants with polar insertions in their cpsIII loci
      supported the hypothesis that the operon is transcribed as a single polycistronic
      message. The translated cpsIII sequences were compared to those of the S.
      agalactiae cpsIa locus, and the primary difference between the operons was found
      to reside in cps(III)H, the putative CPS polymerase gene. Expression of cps(III)H
      in a type Ia strain resulted in suppression of CPS Ia synthesis and in production
      of a CPS which reacted with type III-specific polyclonal antibody. Likewise,
      expression of the putative type Ia polymerase gene in a type III strain reduced
      synthesis of type III CPS with production of a type Ia immunoreactive capsule.
      Based on the similar structures of the oligosaccharide repeating units of the
      type Ia and III capsules, our observations demonstrated that cps(Ia)H and
      cps(III)H encoded the type Ia and III CPS polymerases, respectively.
      Additionally, these findings suggested that a single gene can confer serotype
      specificity in organisms that produce complex polysaccharides.

PMID- 10913083
TI  - Mutational analysis of the tra locus of the broad-host-range Streptomyces plasmid
      pIJ101.
AB  - The tra gene of Streptomyces lividans plasmid pIJ101 encodes a 621-amino-acid
      protein that can mediate both plasmid transfer and the interbacterial transfer of
      chromosomal genes (i.e., chromosome-mobilizing ability [Cma]) during mating. Here
      we report the results of in-frame insertional mutagenesis studies aimed at
      defining regions of Tra required for these functions. While hexameric linker
      insertions throughout the tra gene affected plasmid and chromosomal gene
      transfer, insertions in a 200-amino-acid region of the Tra protein that contains
      presumed nucleotide-binding motifs and that is widely conserved among a
      functionally diverse family of bacterial and plasmid proteins (K. J. Begg, S. J.
      Dewar, and W. D. Donachie, J. Bacteriol. 177:6211-6222, 1995) had especially
      prominent effects on both functions. Insertions near the N terminus of Tra
      reduced Cma for either circular or linear host chromosomes to a much greater
      extent than pIJ101 plasmid transfer. Our results suggest that Cma involves Tra
      functions incremental to those needed for plasmid DNA transfer.

PMID- 10913084
TI  - VirB6 is required for stabilization of VirB5 and VirB3 and formation of VirB7
      homodimers in Agrobacterium tumefaciens.
AB  - VirB6 from Agrobacterium tumefaciens is an essential component of the type IV
      secretion machinery for T pilus formation and genetic transformation of plants.
      Due to its predicted topology as a polytopic inner membrane protein, it was
      proposed to form the transport pore for cell-to-cell transfer of genetic material
      and proteinaceous virulence factors. Here, we show that the absence of VirB6
      leads to reduced cellular levels of VirB5 and VirB3, which were proposed to
      assist T pilus formation as minor component(s) or assembly factor(s),
      respectively. Overexpression of virB6 in trans restored levels of cell-bound and
      T pilus-associated VirB5 to wild type but did not restore VirB3 levels. Thus,
      VirB6 has a stabilizing effect on VirB5 accumulation, thereby regulating T pilus
      assembly. In the absence of VirB6, cell-bound VirB7 monomers and VirB7-VirB9
      heterodimers were reduced and VirB7 homodimer formation was abolished. This
      effect could not be restored by expression of VirB6 in trans. Expression of TraD,
      a component of the transfer machinery of the IncN plasmid pKM101, with
      significant sequence similarity to VirB6, restored neither protein levels nor
      bacterial virulence but partly permitted T pilus formation in a virB6 deletion
      strain. VirB6 may therefore regulate T pilus formation by direct interaction with
      VirB5, and wild-type levels of VirB3 and VirB7 homodimers are not required.

PMID- 10913085
TI  - Inactivation of the stress- and starvation-inducible gls24 operon has a
      pleiotrophic effect on cell morphology, stress sensitivity, and gene expression
      in Enterococcus faecalis.
AB  - Enterococcus faecalis induces the synthesis of at least 42 proteins during 24 h
      of glucose starvation. Because of its induction during carbohydrate and complete
      starvation (incubation in tap water) and CdCl(2) and bile salts stresses, one of
      these proteins (Gls24) was qualified as a "general stress protein" and was
      analyzed at the molecular level. Its corresponding gene, gls24, seems to be the
      penultimate gene of an operon composed, altogether, of six open reading frames
      (ORFs). The ORF preceding gls24 (orf4) showed very strong identity with gls24.
      The deduced polypeptides of these two genes showed similarity with a 20-kDa
      hypothetical protein from Lactococcus lactis and an alkaline stress protein from
      Staphylococcus aureus with no previously known biological significance. Data from
      the operon sequence and Northern analysis led to the conclusions that (i) gls24
      possesses its own promoter which is especially induced at the onset of starvation
      and (ii) the operon promoter is stress inducible in exponential-phase cells. A
      mutation in the gls24 gene led to a severe reduction of growth rate and reduction
      of survival against 0.3% bile salts in the 24-h-starved cells compared to the
      wild-type strain. Moreover, the chain length of the mutant is significantly
      reduced during growth. These results argue strongly for a role of the protein
      Gls24 and/or GlsB in morphological changes and in stress tolerance in E.
      faecalis. Comparison of two-dimensional protein gels from wild-type cells with
      those from gls24 mutant cells revealed a pleiotropic effect of the mutation on
      gene expression. At least nine proteins were present in larger amounts in the
      mutant. For six of them, the corresponding N-terminal microsequence has been
      obtained. Three of these sequences map in genes coding for L-lactate
      dehydrogenase, lipoamide dehydrogenase, and pyruvate decarboxylase, all involved
      in pyruvate metabolism.

PMID- 10913086
TI  - Elevated levels of synthesis of over 20 proteins results after mutation of the
      Rhizobium leguminosarum exopolysaccharide synthesis gene pssA.
AB  - The protein expression profiles of Rhizobium leguminosarum strains in response to
      specific genetic perturbations in exopolysaccharide (EPS) biosynthesis genes were
      examined using two-dimensional gel electrophoresis. Lesions in either pssA, pssD,
      or pssE of R. leguminosarum bv. viciae VF39 or in pssA of R. leguminosarum bv.
      trifolii ANU794 not only abolished the capacity of these strains to synthesize
      EPS but also had a pleiotropic effect on protein synthesis levels. A minimum of
      22 protein differences were observed for the two pssA mutant strains. The
      differences identified in the pssD and pssE mutants of strain VF39 were a
      distinct subset of the same protein synthesis changes that occurred in the pssA
      mutant. The pssD and pssE mutant strains shared identical alterations in the
      proteins synthesized, suggesting that they share a common function in the
      biosynthesis of EPS. In contrast, a pssC mutant that produces 38% of the EPS
      level of the parental strain showed no differences in its protein synthesis
      patterns, suggesting that the absence of EPS itself was contributing to the
      changes in protein synthesis and that there may be a complex interconnection of
      the EPS biosynthetic pathway with other metabolic pathways. Genetic
      complementation of pssA can restore wild-type protein synthesis levels,
      indicating that many of the observed differences in protein synthesis are also a
      specific response to a dysfunctional PssA. The relevance of these proteins, which
      are grouped as members of the pssA mutant stimulon, remains unclear, as the
      majority lacked a homologue in the current sequence databases and therefore
      possibly represent a novel functional network(s). These findings have illustrated
      the potential of proteomics to reveal unexpected higher-order processes of
      protein function and regulation that arise from mutation. In addition, it is
      evident that enzymatic pathways and regulatory networks are more interconnected
      and more sensitive to structural changes in the cell than is often appreciated.
      In these cases, linking the observed phenotype directly to the mutated gene can
      be misleading, as the phenotype could be attributable to downstream effects of
      the mutation.

PMID- 10913087
TI  - Role of the Pseudomonas aeruginosa oxyR-recG operon in oxidative stress defense
      and DNA repair: OxyR-dependent regulation of katB-ankB, ahpB, and ahpC-ahpF.
AB  - Pseudomonas aeruginosa possesses an extensive armament of genes involved in
      oxidative stress defense, including katB-ankB, ahpB, and ahpC-ahpF. Transcription
      of these genes was regulated in response to H(2)O(2), paraquat, or organic
      peroxides. Expression of katB-lacZ and the observed KatB catalase levels in P.
      aeruginosa PAO1 were induced up to 250-fold after exposure to oxidative stress
      generating compounds. Also, ahpB-lacZ and ahpC-lacZ expression was 90- and 3-fold
      higher, respectively, upon exposure to paraquat. The dose- and time-response
      curves revealed that 1 microM paraquat was sufficient for half-maximal activation
      of each reporter fusion within 5 min of exposure. Expression of these genes was
      not observed in a DeltaoxyR mutant, indicating that OxyR was essential for this
      response. The transcriptional start sites of katB-ankB, ahpB, and ahpC-ahpF were
      mapped, putative OxyR-binding sites were identified upstream of the -35 promoter
      elements, and direct binding of purified OxyR protein to these target promoters
      was demonstrated. The oxyR mutant was hypersusceptible to oxidative stress
      generating agents, including H(2)O(2) and paraquat, in spite of total KatA
      catalase activity being comparable to that of the wild type. The oxyR phenotype
      was fully complemented by a plasmid containing the oxyR gene, while any of the
      katB, ahpB, or ahpCF genes alone resulted in only marginal complementation.
      Increased katB-lacZ expression and higher KatB catalase levels were detected in a
      DeltaahpCF background compared to wild-type bacteria, suggesting a compensatory
      function for KatB in the absence of AhpCF. In P. aeruginosa, oxyR is located
      upstream of recG, encoding a putative DNA repair enzyme. oxyR-lacZ and recG-lacZ
      reporter activities and oxyR-recG mRNA analysis showed that oxyR and recG are
      organized in an operon and expressed constitutively with regard to oxidative
      stress from a single promoter upstream of oxyR. Mutants affected in recG but not
      oxyR were dramatically impaired in DNA damage repair as measured by sensitivity
      to UV irradiation. In conclusion, we present evidence that the oxyR-recG locus is
      essential for oxidative stress defense and for DNA repair.

PMID- 10913088
TI  - AnkB, a periplasmic ankyrin-like protein in Pseudomonas aeruginosa, is required
      for optimal catalase B (KatB) activity and resistance to hydrogen peroxide.
AB  - In this study, we have cloned the ankB gene, encoding an ankyrin-like protein in
      Pseudomonas aeruginosa. The ankB gene is composed of 549 bp encoding a protein of
      183 amino acids that possesses four 33-amino-acid ankyrin repeats that are a
      hallmark of erythrocyte and brain ankyrins. The location of ankB is 57 bp
      downstream of katB, encoding a hydrogen peroxide-inducible catalase, KatB.
      Monomeric AnkB is a 19.4-kDa protein with a pI of 5.5 that possesses 22 primarily
      hydrophobic amino acids at residues 3 to 25, predicting an inner-membrane
      spanning motif with the N terminus in the cytoplasm and the C terminus in the
      periplasm. Such an orientation in the cytoplasmic membrane and, ultimately,
      periplasmic space was confirmed using AnkB-BlaM and AnkB-PhoA protein fusions.
      Circular dichroism analysis of recombinant AnkB minus its signal peptide revealed
      a secondary structure that is approximately 65% alpha-helical. RNase protection
      and KatB- and AnkB-LacZ translational fusion analyses indicated that katB and
      ankB are part of a small operon whose transcription is induced dramatically by
      H(2)O(2), and controlled by the global transactivator OxyR. Interestingly, unlike
      the spherical nature of ankyrin-deficient erythrocytes, the cellular morphology
      of an ankB mutant was identical to that of wild-type bacteria, yet the mutant
      produced more membrane vesicles. The mutant also exhibited a fourfold reduction
      in KatB activity and increased sensitivity to H(2)O(2), phenotypes that could be
      complemented in trans by a plasmid constitutively expressing ankB. Our results
      suggest that AnkB may form an antioxidant scaffolding with KatB in the periplasm
      at the cytoplasmic membrane, thus providing a protective lattice work for optimal
      H(2)O(2) detoxification.

PMID- 10913089
TI  - A protease-resistant catalase, KatA, released upon cell lysis during stationary
      phase is essential for aerobic survival of a Pseudomonas aeruginosa oxyR mutant
      at low cell densities.
AB  - A Pseudomonas aeruginosa oxyR mutant was dramatically sensitive to H(2)O(2),
      despite possessing wild-type catalase activity. Oxygen-dependent oxyR phenotypes
      also included an inability to survive aerobic serial dilution in Luria broth and
      to resist aminoglycosides. Plating the oxyR mutant after serial dilution in its
      own spent culture supernatant, which contained the major catalase KatA, or under
      anaerobic conditions allowed for survival. KatA was resistant to sodium dodecyl
      sulfate, proteinase K, pepsin, trypsin, chymotrypsin and the neutrophil protease
      cathepsin G. When provided in trans and expressed constitutively, the OxyR
      regulated genes katB, ahpB, and ahpCF could not restore both the serial dilution
      defect and H(2)O(2) resistance; only oxyR itself could do so. The aerobic
      dilution defect could be complemented, in part, by only ahpB and ahpCF,
      suggesting that the latter gene products could possess a catalase-like activity.
      Aerobic Luria broth was found to generate approximately 1.2 microM H(2)O(2) min(
      1) via autoxidation, a level sufficient to kill serially diluted oxyR and oxyR
      katA bacteria and explain the molecular mechanism behind the aerobic serial
      dilution defect. Taken together, our results indicate that inactivation of OxyR
      renders P. aeruginosa exquisitely sensitive to both H(2)O(2) and aminoglycosides,
      which are clinically and environmentally important antimicrobials.

PMID- 10913090
TI  - Identification and characterization of genes required for early Myxococcus
      xanthus developmental gene expression.
AB  - Starvation and cell density regulate the developmental expression of Myxococcus
      xanthus gene 4521. Three classes of mutants allow expression of this
      developmental gene during growth on nutrient agar, such that colonies of strains
      containing a Tn5 lac Omega4521 fusion are Lac(+). One class of these mutants
      inactivates SasN, a negative regulator of 4521 expression; another class
      activates SasS, a sensor kinase-positive regulator of 4521 expression; and a
      third class blocks lipopolysaccharide (LPS) O-antigen biosynthesis. To identify
      additional positive regulators of 4521 expression, 11 Lac(-) TnV. AS transposon
      insertion mutants were isolated from a screen of 18,000 Lac(+) LPS O-antigen
      mutants containing Tn5 lac Omega4521 (Tc(r)). Ten mutations identified genes that
      could encode positive regulators of 4521 developmental expression based on their
      ability to abolish 4521 expression during development in the absence of LPS O
      antigen and in an otherwise wild-type background. Eight of these mutations mapped
      to the sasB locus, which encodes the known 4521 regulators SasS and SasN. One
      mapped to sasS, whereas seven identified new genes. Three mutations mapped to a
      gene encoding an NtrC-like response regulator homologue, designated sasR, and
      four others mapped to a gene designated sasP. One mutation, designated ssp10,
      specifically suppressed the LPS O-antigen defect; the ssp10 mutation had no
      effect on 4521 expression in an otherwise wild-type background but reduced 4521
      developmental expression in the absence of LPS O antigen to a level close to that
      of the parent strain. All of the mutations except those in sasP conferred defects
      during growth and development. These data indicate that a number of elements are
      required for 4521 developmental expression and that most of these are necessary
      for normal growth and fruiting body development.

PMID- 10913091
TI  - Molecular identification of oligoalginate lyase of Sphingomonas sp. strain A1 as
      one of the enzymes required for complete depolymerization of alginate.
AB  - A bacterium, Sphingomonas sp. strain A1, can incorporate alginate into cells
      through a novel ABC (ATP-binding cassette) transporter system specific to the
      macromolecule. The transported alginate is depolymerized to di- and
      trisaccharides by three kinds of cytoplasmic alginate lyases (A1-I [66 kDa], A1
      II [25 kDa], and A1-III [40 kDa]) generated from a single precursor through
      posttranslational autoprocessing. The resultant alginate oligosaccharides were
      degraded to monosaccharides by cytoplasmic oligoalginate lyase. The enzyme and
      its gene were isolated from the bacterial cells grown in the presence of
      alginate. The purified enzyme was a monomer with a molecular mass of 85 kDa and
      cleaved glycosidic bonds not only in oligosaccharides produced from alginate by
      alginate lyases but also in polysaccharides (alginate, polymannuronate, and
      polyguluronate) most efficiently at pH 8.0 and 37 degrees C. The reaction
      catalyzed by the oligoalginate lyase was exolytic and thought to play an
      important role in the complete depolymerization of alginate in Sphingomonas sp.
      strain A1. The gene for this novel enzyme consisted of an open reading frame of
      2,286 bp encoding a polypeptide with a molecular weight of 86,543 and was located
      downstream of the genes coding for the precursor of alginate lyases (aly) and the
      ABC transporter (algS, algM1, and algM2). This result indicates that the genes
      for proteins required for the transport and complete depolymerization of alginate
      are assembled to form a cluster.

PMID- 10913092
TI  - Vibrio fischeri lux genes play an important role in colonization and development
      of the host light organ.
AB  - The bioluminescent bacterium Vibrio fischeri and juveniles of the squid Euprymna
      scolopes specifically recognize and respond to one another during the formation
      of a persistent colonization within the host's nascent light-emitting organ. The
      resulting fully developed light organ contains brightly luminescing bacteria and
      has undergone a bacterium-induced program of tissue differentiation, one
      component of which is a swelling of the epithelial cells that line the symbiont
      containing crypts. While the luminescence (lux) genes of symbiotic V. fischeri
      have been shown to be highly induced within the crypts, the role of these genes
      in the initiation and persistence of the symbiosis has not been rigorously
      examined. We have constructed and examined three mutants (luxA, luxI, and luxR),
      defective in either luciferase enzymatic or regulatory proteins. All three are
      unable to induce normal luminescence levels in the host and, 2 days after
      initiating the association, had a three- to fourfold defect in the extent of
      colonization. Surprisingly, these lux mutants also were unable to induce swelling
      in the crypt epithelial cells. Complementing, in trans, the defect in light
      emission restored both normal colonization capability and induction of swelling.
      We hypothesize that a diminished level of oxygen consumption by a luciferase
      deficient symbiotic population is responsible for the reduced fitness of lux
      mutants in the light organ crypts. This study is the first to show that the
      capacity for bioluminescence is critical for normal cell-cell interactions
      between a bacterium and its animal host and presents the first examples of V.
      fischeri genes that affect normal host tissue development.

PMID- 10913093
TI  - Escherichia coli DNA polymerase IV mutator activity: genetic requirements and
      mutational specificity.
AB  - The dinB gene of Escherichia coli is known to be involved in the untargeted
      mutagenesis of lambda phage. Recently, we have demonstrated that this damage
      inducible and SOS-controlled gene encodes a novel DNA polymerase, DNA Pol IV,
      which is able to dramatically increase the untargeted mutagenesis of F' plasmid.
      At the amino acid level, DNA Pol IV shares sequence homologies with E. coli UmuC
      (DNA Pol V), Rev1p, and Rad30p (DNA polymerase eta) of Saccharomyces cerevisiae
      and human Rad30A (XPV) proteins, all of which are involved in translesion DNA
      synthesis. To better characterize the Pol IV-dependent untargeted mutagenesis,
      i.e., the DNA Pol IV mutator activity, we analyzed the genetic requirements of
      this activity and determined the forward mutation spectrum generated by this
      protein within the cII gene of lambda phage. The results indicated that the DNA
      Pol IV mutator activity is independent of polA, polB, recA, umuDC, uvrA, and mutS
      functions. The analysis of more than 300 independent mutations obtained in the
      wild-type or mutS background revealed that the mutator activity clearly promotes
      single-nucleotide substitutions as well as one-base deletions in the ratio of
      about 1:2. The base changes were strikingly biased for substitutions toward G:C
      base pairs, and about 70% of them occurred in 5'-GX-3' sequences, where X
      represents the base (T, A, or C) that is mutated to G. These results are
      discussed with respect to the recently described biochemical characteristics of
      DNA Pol IV.

PMID- 10913094
TI  - An A-factor-dependent extracytoplasmic function sigma factor (sigma(AdsA)) that
      is essential for morphological development in Streptomyces griseus.
AB  - A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma-butyrolactone) at an extremely
      low concentration triggers streptomycin production and aerial mycelium formation
      in Streptomyces griseus. A-factor induces the expression of an A-factor-dependent
      transcriptional activator, AdpA, essential for both morphological and
      physiological differentiation by binding to the A-factor receptor protein ArpA,
      which has bound and repressed the adpA promoter, and dissociating it from the
      promoter. Nine DNA fragments that were specifically recognized and bound by
      histidine-tagged AdpA were isolated by cycles of a gel mobility shift-PCR method.
      One of them was located in front of a gene encoding an extracytoplasmic function
      sigma factor belonging to a subgroup of the primary sigma(70) family. The cloned
      gene was named AdpA-dependent sigma factor gene (adsA), and the gene product was
      named sigma(AdsA). Transcription of adsA depended on A-factor and AdpA, since
      adsA was transcribed at a very low and constant level in an A-factor-deficient
      mutant strain or in an adpA-disrupted strain. Consistent with this, transcription
      of adsA was greatly enhanced at or near the timing of aerial hyphae formation, as
      determined by low-resolution S1 nuclease mapping. High-resolution S1 mapping
      determined the transcriptional start point 82 nucleotides upstream of the
      translational start codon. DNase I footprinting showed that AdpA bound both
      strands symmetrically between the transcriptional start point and the
      translational start codon; AdpA protected the antisense strand from positions +7
      to +41 with respect to the transcriptional start point and the sense strand from
      positions +12 to +46. A weak palindrome was found in the AdpA-binding site. The
      unusual position bound by AdpA as a transcriptional activator, in relation to the
      promoter, suggested the presence of a mechanism by which AdpA activates
      transcription of adsA in some unknown way. Disruption of the chromosomal adsA
      gene resulted in loss of aerial hyphae formation but not streptomycin or yellow
      pigment production, indicating that sigma(AdsA) is involved only in morphological
      development and not in secondary metabolic function. The presence of a single
      copy in each of the Streptomyces species examined by Southern hybridization
      suggests a common role in morphogenesis in this genus.

PMID- 10913095
TI  - sigma(BldN), an extracytoplasmic function RNA polymerase sigma factor required
      for aerial mycelium formation in Streptomyces coelicolor A3(2).
AB  - Sporulation mutants of Streptomyces coelicolor appear white because they are
      defective in the synthesis of the gray polyketide spore pigment, and such white
      (whi) mutants have been used to define 13 sporulation loci. whiN, one of five new
      whi loci identified in a recent screen of NTG (N-methyl-N'-nitro-N
      nitrosoguanidine)-induced whi strains (N. J. Ryding et al., J. Bacteriol.
      181:5419-5425, 1999), was defined by two mutants, R112 and R650. R650 produced
      frequent spores that were longer than those of the wild type. In contrast, R112
      produced long, straight, undifferentiated hyphae, although rare spore chains were
      observed, sometimes showing highly irregular septum placement. Subcloning and
      sequencing showed that whiN encodes a member of the extracytoplasmic function
      subfamily of RNA polymerase sigma factors and that the sigma factor has an
      unusual N-terminal extension of approximately 86 residues that is not present in
      other sigma factors. A constructed whiN null mutant failed to form aerial
      mycelium (the "bald" phenotype) and, as a consequence, whiN was renamed bldN.
      This observation was not totally unexpected because, on some media, the R112
      point mutant produced substantially less aerial mycelium than its parent, M145.
      The bldN null mutant did not fit simply into the extracellular signaling cascade
      proposed for S. coelicolor bld mutants. Expression of bldN was analyzed during
      colony development in wild-type and aerial mycelium-deficient bld strains. bldN
      was transcribed from a single promoter, bldNp. bldN transcription was
      developmentally regulated, commencing approximately at the time of aerial
      mycelium formation, and depended on bldG and bldH, but not on bldA, bldB, bldC,
      bldF, bldK, or bldJ or on bldN itself. Transcription from the p1 promoter of the
      response-regulator gene bldM depended on bldN in vivo, and the bldMp1 promoter
      was shown to be a direct biochemical target for sigma(BldN) holoenzyme in vitro.

PMID- 10913096
TI  - Regulation of expression of the yiaKLMNOPQRS operon for carbohydrate utilization
      in Escherichia coli: involvement of the main transcriptional factors.
AB  - The yiaKLMNOPQRS (yiaK-S) gene cluster of Escherichia coli is believed to be
      involved in the utilization of a hitherto unknown carbohydrate which generates
      the intermediate L-xylulose. Transcription of yiaK-S as a single message from the
      unique promoter found upstream of yiaK is proven in this study. The 5' end has
      been located at 60 bp upstream from the ATG. Expression of the yiaK-S operon is
      controlled in the wild-type strain by a repressor encoded by yiaJ. No inducer
      molecule of the yiaK-S operon has been identified among over 80 carbohydrate or
      derivative compounds tested, the system being expressed only in a mutant strain
      lacking the YiaJ repressor. The lacZ transcriptional fusions in the genetic
      background of the mutant strain revealed that yiaK-S is modulated by the
      integration host factor and by the cyclic AMP (cAMP)-cAMP receptor protein (Crp)
      activator complex. A twofold increase in the induction was observed during
      anaerobic growth, which was independent of ArcA or Fnr. Gel mobility shift assays
      showed that the YiaJ repressor binds to a promoter fragment extending from -50 to
      +121. These studies also showed that the cAMP-Crp complex can bind to two
      different sites. The lacZ transcriptional fusions of different fragments of the
      promoter demonstrated that binding of cAMP-Crp to the Crp site 1, centered at 
      106, is essential for yiaK-S expression. The 5' end of the yiaJ gene was
      determined, and its promoter region was found to overlap with the divergent yiaK
      S promoter. Expression of yiaJ is autogenously regulated and reduced by the
      binding of Crp-cAMP to the Crp site 1 of the yiaK-S promoter.

PMID- 10913097
TI  - Role of the yiaR and yiaS genes of Escherichia coli in metabolism of endogenously
      formed L-xylulose.
AB  - Genes yiaP and yiaR of the yiaKLMNOPQRS cluster of Escherichia coli are required
      for the metabolism of the endogenously formed L-xylulose, whereas yiaS is
      required for this metabolism only in araD mutants. Like AraD, YiaS was shown to
      have L-ribulose-5-phosphate 4-epimerase activity. Similarity of YiaR to several 3
      epimerases suggested that this protein could catalyze the conversion of L
      xylulose-5-phosphate into L-ribulose-5-phosphate, thus completing the pathway
      between L-xylulose and the general metabolism.

PMID- 10913098
TI  - A carboxy-terminal 16-amino-acid region of sigma(38) of Escherichia coli is
      important for transcription under high-salt conditions and sigma activities in
      vivo.
AB  - sigma(38) (or sigma(S), the rpoS gene product) is a sigma subunit of RNA
      polymerase in Escherichia coli and directs transcription from a number of
      stationary-phase promoters as well as osmotically inducible promoters. In this
      study, we analyzed the function of the carboxy-terminal 16-amino-acid region of
      sigma(38) (residues 315 to 330), which is well conserved among the rpoS gene
      products of enteric bacterial species. Truncation of this region was shown to
      result in the loss of sigma activity in vivo using promoter-lacZ fusion
      constructs, but the mutant sigma(38) retained the binding activity in vivo to the
      core enzyme. The in vitro transcription analysis revealed that the transcription
      activity of sigma(38) holoenzyme under high potassium glutamate concentrations
      was significantly decreased by the truncation of the carboxy-terminal tail
      element.

PMID- 10913099
TI  - Demonstration of a novel glycolytic pathway in the hyperthermophilic archaeon
      Thermococcus zilligii by (13)C-labeling experiments and nuclear magnetic
      resonance analysis.
AB  - The operation of a novel glycolytic pathway was demonstrated in nongrowing cells
      of Thermococcus zilligii by analysis of the isotopic enrichment in the end
      products derived from fermentation of (13)C-labeled glucose. The new pathway
      involved the formation of formate, derived from C-1 in glucose, via cleavage of a
      six-carbon carboxylic acid.

PMID- 10913100
TI  - Effects of the Calvin cycle on nicotinamide adenine dinucleotide concentrations
      and redox balances of Xanthobacter flavus.
AB  - The levels of reduced and oxidized nicotinamide adenine dinucleotides were
      determined in Xanthobacter flavus during a transition from heterotrophic to
      autotrophic growth. Excess reducing equivalents are rapidly dissipated following
      induction of the Calvin cycle, indicating that the Calvin cycle serves as a sink
      for excess reducing equivalents. The physiological data support the conclusion
      previously derived from molecular studies in that expression of the Calvin cycle
      genes is controlled by the intracellular concentration of NADPH.

PMID- 10913101
TI  - Developmental regulation of the cell division protein FtsZ in Anabaena sp. strain
      PCC 7120, a cyanobacterium capable of terminal differentiation.
AB  - Heterocysts are terminally differentiated cells devoted to nitrogen fixation in
      the filamentous cyanobacterium Anabaena sp. strain PCC 7120. We show here that
      the cell division protein FtsZ is present in vegetative cells but undetectable in
      heterocysts. These results provide a first rational explanation for the inability
      of mature heterocysts to undergo cell division.

PMID- 10913102
TI  - Flavonoid-induced expression of a symbiosis-related gene in the cyanobacterium
      Nostoc punctiforme.
AB  - The flavonoid naringin was found to induce the expression of hrmA, a gene with a
      symbiotic phenotype in the cyanobacterium Nostoc punctiforme. A comparative
      analysis of several flavonoids revealed the 7-O-neohesperidoside, 4'-OH, and C-2
      C-3 double bond in naringin as structural determinants of its hrmA-inducing
      activity.

PMID- 10913104
TI  - 3-Deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase of Legionella pneumophila
      transfers two kdo residues to a structurally different lipid A precursor of
      Escherichia coli.
AB  - The 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo) transferase gene of Legionella
      pneumophila was cloned and sequenced. Despite remarkable structural differences
      in lipid A, the gene complemented a corresponding Escherichia coli mutant and was
      shown to encode a bifunctional enzyme which transferred 2 Kdo residues to a lipid
      A acceptor of E. coli.

PMID- 10913105
TI  - Identification, expression, and characterization of Escherichia coli guanine
      deaminase.
AB  - Using the human cDNA sequence corresponding to guanine deaminase, the Escherichia
      coli genome was scanned using the Basic Local Alignment Search Tool (BLAST), and
      a corresponding 439-residue open reading frame of unknown function was identified
      as having 36% identity to the human protein. The putative gene was amplified,
      subcloned into the pMAL-c2 vector, expressed, purified, and characterized
      enzymatically. The 50.2-kDa protein catalyzed the conversion of guanine to
      xanthine, having a K(m) of 15 microM with guanine and a k(cat) of 3.2 s(-1). The
      bacterial enzyme shares a nine-residue heavy metal binding site with human
      guanine deaminase, PG[FL]VDTHIH, and was found to contain approximately 1 mol of
      zinc per mol of subunit of protein. The E. coli guanine deaminase locus is 3'
      from an open reading frame which shows homology to a bacterial purine base
      permease.

PMID- 10913103
TI  - An oligoribonuclease gene in Streptomyces griseus.
AB  - In Streptomyces griseus, A-factor (2-isocapryloyl-3R-hydroxymethyl-gamma
      butyrolactone) serves as a microbial hormone that switches on many genes required
      for streptomycin production and morphological development. An open reading frame
      (Orf1) showing high sequence similarity to oligoribonucleases of various origins
      is present just downstream of adpA, one of the A-factor-dependent genes. Orf1 was
      named OrnA (oligoribonuclease A) because it showed 3'-to-5' exo-oligoribonuclease
      activity, releasing [(32)P]CMP from ApCpC[(32)P]pC used as a substrate. Reverse
      transcription-PCR and S1 nuclease mapping analyses revealed that ornA was
      transcribed from two promoters; one was a developmentally regulated, A-factor
      dependent promoter in front of adpA, and the other was a constitutive promoter in
      front of the ornA coding sequence. Transcription of ornA was thus additively
      enhanced at the initiation stage for secondary metabolism and aerial mycelium
      formation. ornA-disrupted strains grew slowly and scarcely formed aerial
      mycelium. ornA homologues were distributed in a wide variety of Streptomyces
      species, including S. coelicolor A3(2), as determined by Southern hybridization
      analysis. Disruption of the ornA homologue in S. coelicolor A3(2) also caused
      phenotypes similar to those of the S. griseus DeltaornA strains. The OrnA
      oligoribonucleases in Streptomyces species are therefore not essential but play
      an important role in vegetative growth and in the initiation of differentiation.

PMID- 10913106
TI  - Sequencing, cloning, and high-level expression of the pfp gene, encoding a PP(i)
      dependent phosphofructokinase from the extremely thermophilic eubacterium
      Dictyoglomus thermophilum.
AB  - The sequencing, cloning, and expression of the pfp gene from Dictyoglomus
      thermophilum, which consists of 1,041 bp and encodes a pyrophosphate-dependent
      phosphofructokinase, are described. A phylogenetic analysis indicates that the
      enzyme is closely related to the pyrophosphate-dependent enzyme from
      Thermoproteus tenax. The recombinant and native enzymes share a high degree of
      similarity for most properties examined.

PMID- 10913107
TI  - Dual functions of Streptococcus salivarius urease.
AB  - A urease-deficient derivative of Streptococcus salivarius 57.I was constructed by
      allelic exchange at the ureC locus. The wild-type strain was protected against
      acid killing through hydrolysis of physiologically relevant concentrations of
      urea, whereas the mutant was not. Also, S. salivarius could use urea as a source
      of nitrogen for growth exclusively through a urease-dependent pathway.

PMID- 10913108
TI  - H-NS-Dependent regulation of flagellar synthesis is mediated by a LysR family
      protein.
AB  - H-NS regulates the flagellar master operon (flhDC) and thus is necessary for
      flagellation of Escherichia coli. However, the molecular mechanism of its
      regulation has remained unknown. Genetic screening of a transposon insertion
      abolishing the H-NS effect revealed a previously unidentified gene, named hdfR,
      encoding a LysR family protein. Binding of purified HdfR to the flhDC promoter
      was demonstrated by a DNA mobility shift assay, indicating that HdfR is a
      transcriptional regulator for the flagellar master operon. Furthermore, the
      expression of the hdfR gene was shown to be negatively regulated by H-NS.

PMID- 10913109
TI  - Novel insertion sequence elements associated with genetic heterogeneity and
      phenotype conversion in Ralstonia solanacearum.
AB  - Three insertion sequences (IS) elements were isolated from the phytopathogen
      Ralstonia solanacearum. Southern hybridization using these IS elements as probes
      revealed hybridization profiles that varied greatly between different strains of
      the pathogen. During a spontaneous phenotype conversion event, the promoter of
      the phcA gene was interrupted by one of these IS elements.

PMID- 10913110
TI  - A novel type of bifunctional inhibitor directed against proteolytic activity and
      receptor/ligand interaction. Cystatin with a urokinase receptor binding site.
AB  - Cancer invasion and metastasis is a process requiring a coordinated series of
      (anti-)adhesive, migratory, and pericellular proteolytic events involving various
      proteases such as urokinase-type plasminogen activator (uPA)/plasmin, cathepsins
      B and L, and matrix metalloproteases. Novel types of double-headed inhibitors
      directed to different tumor-associated proteolytic systems were generated by
      substitution of a loop in chicken cystatin, which is nonessential for cysteine
      protease inhibition, with uPA-derived peptides covering the human uPA receptor
      binding sequence uPA-(19-31). The inhibition constants of these hybrids toward
      cysteine proteases are similar to those of wild-type cystatin (K(i), papain (pm),
      1.9-2.4; K(i), cathepsin B (nm), 1.0-1.7; K(i), cathepsin L (pm), 0.12-0.61).
      FACS analyses revealed that the hybrids compete for binding of uPA to the cell
      surface-associated uPA receptor (uPAR) expressed on human U937 cells. The
      simultaneous interaction of the hybrid molecules with papain and uPAR was
      analyzed by surface plasmon resonance. The measured K(D) value of a papain-bound
      cystatin variant harboring the uPAR binding sequence of uPA (chCys-uPA-(19-31))
      and soluble uPAR was 17 nm (K(D) value for uPA/uPAR interaction, 5 nm). These
      results indicate that cystatins with a uPAR binding site are efficient inhibitors
      of cysteine proteases and uPA/uPAR interaction at the same time. Therefore, these
      compact and small bifunctional inhibitors may represent promising agents for the
      therapy of solid tumors.

PMID- 10913111
TI  - NBS1 and TRF1 colocalize at promyelocytic leukemia bodies during late S/G2 phases
      in immortalized telomerase-negative cells. Implication of NBS1 in alternative
      lengthening of telomeres.
AB  - Nijmegen breakage syndrome, a chromosomal instability disorder, is characterized
      in part by cellular hypersensitivity to ionizing radiation. The NBS1 gene
      product, p95 (NBS1 or nibrin) forms a complex with Rad50 and Mre11. Cells
      deficient in the formation of this complex are defective in DNA double-strand
      break repair, cell cycle checkpoint control, and telomere length maintenance. How
      the NBS1 complex is involved in telomere length maintenance remains unclear. Here
      we show that the C-terminal region of NBS1 interacts directly with a telomere
      repeat binding factor, TRF1, by both yeast two-hybrid and in vivo DNA
      coimmunoprecipitation assays. NBS1 and Mre11 colocalize with TRF1 at
      promyelocytic leukemia (PML) nuclear bodies in immortalized telomerase-negative
      cell lines, but rarely in telomerase-positive cell lines. The translocation of
      NBS1 to PML bodies occurs specifically during late S to G(2) phases of the cell
      cycle and coincides with active DNA synthesis in these NBS1-containing PML
      bodies. These results suggest that NBS1 may be involved in alternative
      lengthening of telomeres in telomerase-negative immortalized cells.

PMID- 10913112
TI  - The role of gamma A/gamma ' fibrinogen in plasma factor XIII activation.
AB  - Factor XIII zymogen activation is a complex series of events that involve
      fibrinogen acting in several different roles. This report focuses on the role of
      fibrinogen as a cofactor in factor XIII activation by thrombin. We demonstrate
      that fibrinogen has two distinct activities that lead to an increased rate of
      factor XIII activation. First, the thrombin proteolytic activity is increased by
      fibrin. The cleavage rates of both a small chromogenic substrate and the factor
      XIII activation peptide are increased in the presence of either the major fibrin
      isoform, gammaA/gammaA fibrin, or a minor variant form, gammaA/gamma' fibrin.
      This enhancement of thrombin activity by fibrin is independent of fibrin
      polymerization and requires only cleavage of the fibrinopeptides. Subsequently,
      gammaA/gamma' fibrinogen accelerates plasma factor XIII activation by a non
      proteolytic mechanism. This increased rate of activation results in a slightly
      more rapid cross-linking of fibrin gammaA and gamma' chains and a significantly
      more rapid cross-linking of fibrin alpha chain multimers. Together, these results
      show that although both forms of fibrin increase the rate of activation peptide
      cleavage by thrombin, gammaA/gamma' fibrinogen also increases the rate of factor
      XIII activation in a non-proteolytic manner. A revised model of factor XIII
      activation is presented below.

PMID- 10913113
TI  - A novel cytosolic dual specificity phosphatase, interacting with glucokinase,
      increases glucose phosphorylation rate.
AB  - A novel protein was cloned from a rat liver cDNA library by interaction with the
      liver glucokinase. This protein contained 339 residues and possessed a canonical
      consensus sequence for a dual specificity phosphatase. The recombinant protein
      was able to dephosphorylate phosphotyrosyl and phosphoseryl/threonyl substrates.
      We called this protein the glucokinase-associated phosphatase (GKAP). The GKAP
      partially dephosphorylated the recombinant glucokinase previously phosphorylated,
      in vitro, by protein kinase A. The GKAP fused with green fluorescent protein was
      located in the cytosol, where glucokinase phosphorylates glucose, and not in the
      nucleus where the glucokinase is retained inactive by the glucokinase regulatory
      protein. More importantly, the GKAP accelerated the glucokinase activity in a
      dose-dependent manner and with a stoichiometry compatible with a physiological
      mechanism. This strongly suggested that the interaction between GKAP and
      glucokinase had a functional significance. The cloning of this novel protein with
      a dual specificity phosphatase activity allows the description of a possible new
      regulatory step in controlling the glycolysis flux.

PMID- 10913114
TI  - GAS41, a highly conserved protein in eukaryotic nuclei, binds to NuMA.
AB  - The yeast two-hybrid system was used to identify binding partners of NuMA, a
      component of the nuclear matrix in interphase cells. By using the C-terminal half
      of NuMA as bait, a human cDNA sequence coding for a 223-amino acid protein with a
      non-helical N-terminal domain and a C-terminal alpha-helical portion was
      identified and fully sequenced. It was identical to GAS41, a sequence amplified
      in human gliomas. The sequence of the homologous Drosophila protein was
      established, and the alignment for GAS41 from nine different species showed that
      GAS41 is a general eukaryotic protein found in species as diverse as Arabidopsis,
      Drosophila, Caenorhabditis elegans, yeast, and man. Northern blot analysis showed
      a single transcript in eight human tissues. A polyclonal antibody to GAS41 showed
      a dotted staining pattern in interphase nuclei and a uniform distribution in
      mitotic cells. A GFP-GAS41 fusion protein displayed equivalent patterns. In vitro
      GAS41 bound to the C-terminal part of the rod region of NuMA, as shown by dot
      overlay and by surface plasmon resonance measurements. The K(d) of the complex
      was 2 x 10(-)(7) m. GAS41 is related to the AF-9 and ENL proteins, which are
      putative transcription factors found as fusion proteins in some acute leukemias.
      The NuMA/GAS41 interaction may provide a link between nuclear structure and gene
      expression.

PMID- 10913115
TI  - Chitin catabolism in the marine bacterium Vibrio furnissii. Identification and
      molecular cloning of a chitoporin.
AB  - Chitin catabolism by the marine bacterium Vibrio furnissii involves many genes
      and proteins, including two unique periplasmic hydrolases, a chitodextrinase and
      a beta-N-acetylglucosaminidase (Keyhani, N. O. , and Roseman, S. (1996) J. Biol.
      Chem. 271, 33414-33424 and 33425-33432). A specific chitoporin in the outer
      membrane may be required for these glycosidases to be accessible to extracellular
      chitooligosaccharides, (GlcNAc)(n), that are produced by chitinases. We report
      here the identification and molecular cloning of such a porin. An outer membrane
      protein, OMP (apparent molecular mass 40 kDa) was expressed when V. furnissii was
      induced by (GlcNAc)(n), n = 2-6, but not by GlcNAc or other sugars. Based on the
      N-terminal sequence of OMP, oligonucleotides were synthesized and used to clone
      the gene, chiP. The deduced amino acid sequence of ChiP is similar to several
      bacterial porins; OMP is a processed form of ChiP. In Escherichia coli, two
      recombinant proteins were observed, corresponding to processed and unprocessed
      forms of ChiP. A null mutant of chiP was constructed in V. furnissii. In contrast
      to the parental strain, the mutant did not grow on (GlcNAc)(3) and transported a
      nonmetabolizable analogue of (GlcNAc)(2) at a reduced rate. These results imply
      that ChiP is a specific chitoporin.

PMID- 10913116
TI  - Chitin catabolism in the marine bacterium Vibrio furnissii. Identification,
      molecular cloning, and characterization of A N, N'-diacetylchitobiose
      phosphorylase.
AB  - The major product of bacterial chitinases is N,N'-diacetylchitobiose or
      (GlcNAc)(2). We have previously demonstrated that (GlcNAc)(2) is taken up
      unchanged by a specific permease in Vibrio furnissii (unlike Escherichia coli).
      It is generally held that marine Vibrios further metabolize cytoplasmic
      (GlcNAc)(2) by hydrolyzing it to two GlcNAcs (i.e. a "chitobiase "). Here we
      report instead that V. furnissii expresses a novel phosphorylase. The gene, chbP,
      was cloned into E. coli; the enzyme, ChbP, was purified to apparent homogeneity,
      and characterized kinetically. The DNA sequence indicates that chbP encodes an 89
      kDa protein. The enzymatic reaction was characterized as follows.
      (GlcNAc)(2)+P(i) GlcNAc-alpha-1-P+GlcNAc K'(cq)=1.0+/-0.2 Reaction 1 The K(m)
      values for the four substrates were in the range 0.3-1 mm. p-Nitrophenyl
      (GlcNAc)(2) was cleaved at 8.5% the rate of (GlcNAc)(2), and p-nitrophenyl (PNP)
      GlcNAc was 36% as active as GlcNAc in the reverse direction. All other compounds
      tested displayed </=1% of the activity of the indicated substrates including: for
      phosphorolysis, higher chitin oliogsaccharides, (GlcNAc)(n), n = 3-5, cellobiose,
      PNP-GlcNAc, and PNP-(GlcNAc)(3); for synthesis, (GlcNAc)(n) (n = 2-5), glucose,
      etc. (GlcNAc)(2) is a major regulator of the chitin catabolic cascade.
      Conceivably GlcNAc-alpha-1-P plays a similar but different role in regulation.

PMID- 10913117
TI  - The chitin disaccharide, N,N'-diacetylchitobiose, is catabolized by Escherichia
      coli and is transported/phosphorylated by the phosphoenolpyruvate:glycose
      phosphotransferase system.
AB  - We have previously reported that wild type strains of Escherichia coli grow on
      the chitin disaccharide N,N'-diacetylchitobiose, (GlcNAc)(2), as the sole source
      of carbon (Keyhani, N. O., and Roseman, S. (1997) Proc. Natl. Acad. Sci., U. S.
      A. 94, 14367-14371). A nonhydrolyzable analogue of (GlcNAc)(2,) methyl beta-N, N'
      [(3)H]diacetylthiochitobioside ([(3)H]Me-TCB), was used to characterize the
      disaccharide transport process, which was found to be mediated by the
      phosphoenolpyruvate:glycose phosphotransferase system (PTS). Here and in the
      accompanying papers (Keyhani, N. O., Boudker, O., and Roseman, S. (2000) J. Biol.
      Chem. 275, 33091-33101; Keyhani, N. O., Bacia, K., and Roseman, S. (2000) J.
      Biol. Chem. 275, 33102-33109; Keyhani, N. O., Rodgers, M., Demeler, B., Hansen,
      J., and Roseman, S. (2000) J. Biol. Chem. 275, 33110-33115), we report that
      transport of [(3)H]Me-TCB and (GlcNAc)(2) involves a specific PTS Enzyme II
      complex, requires Enzyme I and HPr of the PTS, and results in the accumulation of
      the sugar derivative as a phosphate ester. The phosphoryl group is linked to the
      C-6 position of the GlcNAc residue at the nonreducing end of the disaccharide.
      The [(3)H]Me-TCB uptake system was induced only by (GlcNAc)(n), n = 2 or 3. The
      apparent K(m) of transport was 50-100 micrometer, and effective inhibitors of
      uptake included (GlcNAc)(n), n = 2 or 3, cellobiose, and other PTS sugars, i.e.
      glucose and GlcNAc. Presumably the PTS sugars inhibit by competing for PTS
      components. Kinetic properties of the transport system are described.

PMID- 10913118
TI  - Isolation and characterization of IIAChb, a soluble protein of the enzyme II
      complex required for the transport/phosphorylation of N, N'-diacetylchitobiose in
      Escherichia coli.
AB  - N,N'-Diacetylchitobiose is transported/phosphorylated in Escherichia coli by the
      (GlcNAc)(2)-specific Enzyme II permease of the phosphoenolpyruvate:glycose
      phosphotransferase system. IIA(Chb), one protein of the Enzyme II complex, was
      cloned and purified to homogeneity. IIA(Chb) and phospho-IIA(Chb) form stable
      homodimers (). Phospho-IIA(Chb) behaves as a typical epsilon2-N (i.e. N-3)
      phospho-His protein. However, the rate constants for hydrolysis of phospho
      IIA(Chb) at pH 8.0 unexpectedly increased 7-fold between 25 and 37 degrees C and
      increased approximately 4-fold with decreasing protein concentration at 37
      degrees C (but not 25 degrees C). The data were explained by thermal denaturation
      studies using CD spectroscopy. IIA(Chb) and phospho-IIA(Chb) exhibit virtually
      identical spectra at 25 degrees C (approximately 80% alpha-helix), but phospho
      IIA(Chb) loses about 30% of its helicity at 37 degrees C, whereas IIA(Chb) shows
      only a slight change. Furthermore, the T(m) for thermal denaturation of IIA(Chb)
      was 54 degrees C, only slightly affected by concentration, whereas the T(m) for
      phospho-IIA(Chb) was much lower, ranging from 40 to 46 degrees C, depending on
      concentration. In addition, divalent cations (Mg(2+), Cu(2+), and Ni(2+)) have a
      dramatic and differential effect on the structure, depending on the state of
      phosphorylation of the protein. Thus, phosphorylation destabilizes IIA(Chb) at 37
      degrees C, potentially affecting the monomer/dimer transition, which correlates
      with its chemical instability at this temperature. The physiological consequences
      of this phenomenon are briefly considered.

PMID- 10913119
TI  - The transport/phosphorylation of N,N'-diacetylchitobiose in Escherichia coli.
      Characterization of phospho-IIB(Chb) and of a potential transition state analogue
      in the phosphotransfer reaction between the proteins IIA(Chb) AND IIB(Chb).
AB  - Enzyme II permeases of the phosphoenolpyruvate:glycose phosphotransferase system
      comprise one to five separately encoded polypeptides, but most contain similar
      domains (IIA, IIB, and IIC). The phosphoryl group is transferred from one domain
      to another, with histidine as the phosphoryl acceptor in IIA and cysteine as the
      acceptor in certain IIB domains. IIB(Chb) is a phosphocarrier in the
      uptake/phosphorylation of the chitin disaccharide, (GlcNAc)(2) by Escherichia
      coli and is unusual because it is separately encoded and soluble. Both the
      crystal and solution structures of a IIB(Chb) mutant (C10S) have been reported.
      In the present studies, homogeneous phospho-IIB(Chb) was isolated, and the
      phosphoryl-Cys linkage was established by (31)P NMR spectroscopy. Rate constants
      for the hydrolysis of phospho-IIB(Chb) plotted versus pH gave the same shape peak
      reported for the model compound, butyl thiophosphate, but was shifted about 4 pH
      units. Evidence is presented for a stable complex between homogeneous
      Cys10SerIIB(Chb) (which cannot be phosphorylated) and phospho-IIA(Chb), but not
      with IIA(Chb). The complex (a tetramer (3)) contains equimolar quantities of the
      two proteins and has been chemically cross-linked. It appears to be an analogue
      of the transition state complex in the reaction: phospho-IIA(Chb) + IIB(Chb) <-->
      IIA(Chb) + phospho-IIB(Chb). This is apparently the first report of the isolation
      of a transition state analogue in a protein-protein phosphotransfer reaction.

PMID- 10913120
TI  - Bcl-xL inhibits cytochrome c release but not mitochondrial depolarization during
      the activation of multiple death pathways by tumor necrosis factor-alpha.
AB  - Cells can respond differently to anti-CD95 antibody treatment. Type I cells show
      strong activation of caspase-8 and directly activate caspase-3. Type II cells
      weakly activate caspase-8 and must amplify their death signal through the
      mitochondria. These cells can be rescued by Bcl-x(L). Here we show that tumor
      necrosis factor-alpha induces both Type I and II pathways, which can be inhibited
      by benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (Z-VAD-fmk) and Bcl-x(L) in
      a cooperative fashion. Death induced in the presence of Z-VAD-fmk was associated
      with a partial inhibition of caspase-8, whereas no effects on cytochrome c
      release, DEVDase activity, and intranucleosomal DNA cleavage were observed. Thus,
      Z-VAD-fmk is likely weakening the death-inducing signaling complex-mediated
      activation of caspase-8 and diverting cells to a Type II pathway. Bcl-x(L)
      cooperates with Z-VAD-fmk by blocking the Type II pathway at the level of
      cytochrome c release. Surprisingly, although Bcl-x(L) was able to block
      cytochrome c release, it was unable to block mitochondrial depolarization,
      suggesting that these are separate events. This suggests that mitochondria occupy
      two places in apoptotic signaling, as initiators of apoptosis through the release
      of cytochrome c as well as a target for effector caspases.

PMID- 10913121
TI  - Expression of recombinant human pregnancy-associated plasma protein-A and
      identification of the proform of eosinophil major basic protein as its
      physiological inhibitor.
AB  - Pregnancy-associated plasma protein-A (PAPP-A), originally known from human
      pregnancy serum, has recently been demonstrated to be a metzincin superfamily
      metalloproteinase involved in normal and pathological insulin-like growth factor
      (IGF) physiology. PAPP-A specifically cleaves IGF-binding protein (IGFBP)-4, one
      of six antagonists of IGF action, which results in release of IGF bound to IGFBP
      4. IGFBP-4 is the only known PAPP-A substrate. Its cleavage by PAPP-A uniquely
      depends on the presence of IGF. We here report mammalian expression and
      purification of recombinant 1547-residue PAPP-A (rPAPP-A). The recombinant
      protein is secreted as a homodimer of about 400 kDa composed of two 200-kDa
      disulfide-bound subunits. Antigenically and functionally, rPAPP-A behaves like
      the native protein. In human pregnancy, PAPP-A is known to circulate as a 500-kDa
      disulfide-bound 2:2 complex with the proform of eosinophil major basic protein
      (proMBP), PAPP-A/proMBP. A comparison between rPAPP-A and pregnancy serum PAPP
      A/proMBP complex surprisingly reveals a difference greater than 100-fold in
      proteolytic activity, showing that proMBP functions as a proteinase inhibitor in
      vivo. We find that polyclonal antibodies against PAPP-A abrogate all detectable
      IGFBP-4 proteolytic activity in pregnancy serum, pointing at PAPP-A as the
      dominating, if not the only, IGFBP-4 proteinase present in the circulation. We
      further show that pregnancy serum and plasma contain traces (<1%) of uncomplexed
      PAPP-A with a much higher specific activity than the PAPP-A/proMBP complex. The
      measurable activity of the PAPP-A/proMBP complex probably results from the
      presence of a minor subpopulation of partly inhibited PAPP-A that exists in a 2:1
      complex with proMBP. Inhibition of PAPP-A by proMBP represents a novel inhibitory
      mechanism with the enzyme irreversibly bound to its inhibitor by disulfide bonds.

PMID- 10913122
TI  - Analytical sedimentation of the IIAChb and IIBChb proteins of the Escherichia
      coli N,N'-diacetylchitobiose phosphotransferase system. Demonstration of a model
      phosphotransfer transition state complex.
AB  - The phosphoenolpyruvate:glycose transferase system (PTS) is a prototypic
      signaling system responsible for the vectorial uptake and phosphorylation of
      carbohydrate substrates. The accompanying papers describe the proteins and
      product of the Escherichia coli N, N-diacetylchitobiose ((GlcNAc)(2)) PTS
      mediated permease. Unlike most PTS transporters, the Chb system is composed of
      two soluble proteins, IIA(Chb) and IIB(Chb), and one transmembrane receptor
      (IIC(Chb)). The oligomeric states of PTS permease proteins and phosphoproteins
      have been difficult to determine. Using analytical ultracentrifugation, both
      dephospho and phosphorylated IIA(Chb) are shown to exist as stable dimers,
      whereas IIB(Chb), phospho-IIB(Chb) and the mutant Cys10SerIIB(Chb) are monomers.
      The mutant protein Cys10SerIIB(Chb) is unable to accept phosphate from phospho
      IIA(Chb) but forms a stable higher order complex with phospho-IIA(Chb) (but not
      with dephospho-IIA(Chb)). The stoichiometry of proteins in the purified complex
      was determined to be 1:1, indicating that two molecules of Cys10SerIIB(Chb) are
      associated with one phospho-IIA(Chb) dimer in the complex. The complex appears to
      be a transition state analogue in the phosphotransfer reaction between the
      proteins. A model is presented that describes the concerted assembly and
      disassembly of IIA(Chb)-IIB(Chb) complexes contingent on phosphorylation
      dependent conformational changes, especially of IIA(Chb).

PMID- 10913123
TI  - A single point mutation in 3-deoxy-D-manno-octulosonate-8-phosphate synthase is
      responsible for temperature sensitivity in a mutant strain of Salmonella
      typhimurium.
AB  - Salmonella typhimurium mutants conditionally deficient in 3-deoxy-d-manno
      octulosonate-8-phosphate (KDO8P) synthase activity play a central role in our
      understanding of lipopolysaccharide function in enteric bacteria. The detailed
      characterization of KDO8P synthase from such a mutant, however, has not been
      previously reported. To address this issue KDO8P synthase from S. typhimurium
      AG701 and from a related temperature-sensitive strain (S. typhimurium AG701i50)
      have been overexpressed in Escherichia coli and purified to homogeneity. The
      enzyme from the temperature-sensitive strain has a single proline to serine
      substitution at position 145, leading to an increase in K(m) for both substrates,
      d-arabinose 5-phosphate and phosphoenolpyruvate. Analytical gel filtration and
      native polyacrylamide gel electrophoresis indicate that this enzyme also has an
      altered oligomeric state. These observations are rationalized through an
      examination of the structure of E. coli KDO8P synthase, which has 93% sequence
      identity to the enzyme from S. typhimurium.

PMID- 10913124
TI  - Distinct polyphosphoinositide binding selectivities for pleckstrin homology
      domains of GRP1-like proteins based on diglycine versus triglycine motifs.
AB  - GRP1 and the related proteins ARNO and cytohesin-1 are ARF exchange factors that
      contain a pleckstrin homology (PH) domain thought to target these proteins to
      cell membranes through binding polyphosphoinositides. Here we show the PH domains
      of all three proteins exhibit relatively high affinity for dioctanoyl
      phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P(3)), with K(D) values of
      0.05, 1.6 and 1.0 micrometer for GRP1, ARNO, and cytohesin-1, respectively.
      However, the GRP1 PH domain was unique among these proteins in its striking
      selectivity for PtdIns(3,4, 5)P(3) versus phosphatidylinositol 4,5-diphosphate
      (PtdIns(4,5)P(2)), for which it exhibits about 650-fold lower apparent affinity.
      Addition of a glycine to the Gly(274)-Gly(275) motif in GRP1 greatly increased
      its binding affinity for PtdIns(4,5)P(2) with little effect on its binding to
      PtdIns(3,4,5)P(3), while deletion of a single glycine in the corresponding
      triglycine motif of the ARNO PH domain markedly reduced its binding affinity for
      PtdIns(4,5)P(2) but not for PtdIns(3,4,5)P(3). In intact cells, the hemagglutinin
      epitope-tagged PH domain of GRP1 was recruited to ruffles in the cell surface in
      response to insulin, as were full-length GRP1 and cytohesin-1, but the PH domain
      of cytohesin-1 was not. These data indicate that the unique diglycine motif in
      the GRP1 PH domain, as opposed to the triglycine in ARNO and cytohesin-1, directs
      its remarkable PtdIns(3,4,5)P(3) binding selectivity.

PMID- 10913125
TI  - Conformational lability of herpesvirus protein VP22.
AB  - The herpesvirus protein VP22 traffics between cells, being exported from
      expressing cells in a non-Golgi-dependent manner and localizing in the nuclei of
      surrounding cells. This transport is retained in certain VP22 fusion proteins,
      making VP22 a candidate for use in macromolecular drug delivery. In an effort to
      understand the physical basis for this activity, we have initiated structural
      studies of VP22.C1, the C-terminal half of VP22, which possesses the full
      transport activity of the native protein. CD and Fourier transform infrared
      analyses indicate a secondary structure consisting of approximately 30% alpha
      helix, 17% beta-sheet, and 51% disordered and turn structure. Unfolding studies
      conducted by CD, differential scanning calorimetry, and fluorescence reveal a
      series of discrete structural transitions in the range of 20-60 degrees C. CD and
      fluorescence studies of interactions between VP22.C1 and divalent cations and
      model polyanions indicate that Mg(2+), Zn(2+), oligonucleotides, and heparin
      interact with the protein, causing changes in secondary structure and thermal
      stability. Additionally, the interaction of VP22.C1 with model lipids was
      examined. Fluorescence titrations of the protein with trans-parinaric acid at
      various temperatures suggest the binding of one to two molecules of parinaric
      acid to VP22.C1 at temperatures >40 degrees C, suggesting the possibility of
      conformation dependent membrane interaction under physiological conditions.

PMID- 10913126
TI  - A naturally occurring steroidogenic factor-1 mutation exhibits differential
      binding and activation of target genes.
AB  - Steroidogenic factor-1 (SF-1) is an orphan nuclear receptor that binds DNA as a
      monomer and regulates the transcription of multiple target genes. A mutation in
      the proximal (P)-box of the first zinc finger of SF-1 (G35E) has been reported to
      cause complete XY sex reversal and adrenal insufficiency. Because this P-box
      region dictates DNA binding specificity, we investigated the effect of this
      mutation on DNA binding and regulation of target genes. Binding of the P-box
      mutant was markedly impaired for most native SF-1 response elements. However,
      mutant SF-1 bound to a subset of response elements containing a CCA AGGTCA motif.
      Mutagenesis studies of response elements revealed that the first nucleotide
      position in the 5'-flanking sequence triplet and the central part of the half
      site dictate DNA binding specificity by the mutant SF-1. Further, introduction of
      a mutation into the SF-1 A-box, which has been proposed to bind to the 5'
      flanking sequence triplet, eliminated binding by mutant SF-1 to all response
      elements tested. These data support the idea that the A-box stabilizes monomeric
      binding by nuclear receptors. This action may be particularly important when P
      box binding affinity is compromised either by mutations in SF-1 or by sequence
      alterations in its binding site.

PMID- 10913127
TI  - Functional comparison of the K+-Cl- cotransporters KCC1 and KCC4.
AB  - The K(+)-Cl(-) cotransporters (KCCs) are members of the cation-chloride
      cotransporter gene family and fall into two phylogenetic subgroups: KCC2 paired
      with KCC4 and KCC1 paired with KCC3. We report a functional comparison in Xenopus
      oocytes of KCC1 and KCC4, widely expressed representatives of these two
      subgroups. KCC1 and KCC4 exhibit differential sensitivity to transport
      inhibitors, such that KCC4 is much less sensitive to bumetanide and furosemide.
      The efficacy of these anion inhibitors is critically dependent on the
      concentration of extracellular K(+), with much higher inhibition in 50 mm K(+)
      versus 2 mm K(+). KCC4 is also uniquely sensitive to 10 mm barium and to 2 mm
      trichlormethiazide. Kinetic characterization reveals divergent affinities for
      K(+) (K(m) values of approximately 25.5 and 17.5 mm for KCC1 and KCC4,
      respectively), probably due to variation within the second transmembrane segment.
      Although the two isoforms have equivalent affinities for Cl(-), they differ in
      the anion selectivity of K(+) transport (Cl(-) > SCN(-) = Br(-) > PO(4)(-3) > I(
      ) for KCC1 and Cl(-) > Br(-) > PO(4)(-3) = I(-) > SCN(-) for KCC4). Both KCCs
      express minimal K(+)-Cl(-) cotransport under isotonic conditions, with
      significant activation by cell swelling under hypotonic conditions. The cysteine
      alkylating agent N-ethylmaleimide activates K(+)-Cl(-) cotransport in isotonic
      conditions but abrogates hypotonic activation, an unexpected dissociation of N
      ethylmaleimide sensitivity and volume sensitivity. Although KCC4 is consistently
      more volume-sensitive, the hypotonic activation of both isoforms is critically
      dependent on protein phosphatase 1. Overall, the functional comparison of these
      cloned K(+)-Cl(-) cotransporters reveals important functional, pharmacological,
      and kinetic differences with both physiological and mechanistic implications.

PMID- 10913128
TI  - Constitutive release of ATP and evidence for major contribution of ecto
      nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular
      nucleotide concentrations.
AB  - Nucleotides are important extracellular signaling molecules. At least five
      mammalian P2Y receptors exist that are specifically activated by ATP, UTP, ADP,
      or UDP. Although the existence of ectoenzymes that metabolize extracellular
      nucleotides is well established, the relative flux of ATP and UTP through their
      extracellular metabolic products remains undefined. Therefore, we have studied
      the kinetics of accumulation and metabolism of endogenous ATP in the
      extracellular medium of four different cell lines. ATP concentrations reached a
      maximum immediately after change of medium and decreased thereafter with a single
      exponential decay (t(1/2);1 approximately;230-40 min). ATP levels did not fall to
      zero but attained a base-line concentration that was independent of the medium
      volume and of the initial ATP concentration. Although the base-line concentration
      of ATP remained stable for up to 12 h, [gamma-(32)P]ATP added to resting cells as
      a radiotracer was completely degraded within 120 min, indicating that steady
      state reflected a basal rate of ATP release balanced by ATP hydrolysis (20-200
      fmol x min(-)(1) x cell(-)(6)). High performance liquid chromatography analysis
      revealed that the gamma-phosphate of ATP was rapidly, although transiently,
      transferred during steady state to species subsequently identified as UTP and
      GTP, indicating the existence of both ecto-nucleoside diphosphokinase activity
      and the accumulation of endogenous UDP and GDP. Conversely, addition of [gamma
      (32)P]UTP to resting cells resulted in transient formation of [gamma-(32)P]ATP,
      indicating phosphorylation of endogenous ADP by nucleoside diphosphokinase. The
      final (32)P-products of [gamma-(32)P]ATP metabolism were [(32)P]orthophosphoric
      acid and a (32)P-labeled species that was further purified and identified as
      [(32)P]inorganic pyrophosphate. In C6 cells, the formation of
      [(32)P]pyrophosphate from [gamma-(32)P]ATP at steady state exceeded by 3-fold
      that of [(32)P]orthophosphate. These results illustrate for the first time a
      constitutive release of ATP and other nucleotides and reveal the existence of a
      complex extracellular metabolic pathway for released nucleotides. In addition to
      the existence of an ecto-ATPase activity, our results suggest a major scavenger
      role of ecto-ATP pyrophosphatase and a transphosphorylating activity of
      nucleoside diphosphokinase.

PMID- 10913129
TI  - Sterol regulatory element-binding protein-1 is regulated by glucose at the
      transcriptional level.
AB  - In vivo studies suggest that sterol regulatory element-binding protein (SREBP)-1
      plays a key role in the up-regulation of lipogenic genes in the livers of animals
      that have consumed excess amounts of carbohydrates. In light of this, we sought
      to use an established mouse hepatocyte cell line, H2-35, to further define the
      mechanism by which glucose regulates nuclear SREBP-1 levels. First, we show that
      these cells transcribe high levels of SREBP-1c that are increased 4-fold upon
      differentiation from a prehepatocyte to a hepatocyte phenotype, making them an
      ideal cell culture model for the study of SREBP-1c induction. Second, we
      demonstrate that the presence of precursor and mature forms of SREBP-1 protein
      are positively regulated by medium glucose concentrations ranging from 5. 5 to 25
      mm and are also regulated by insulin, with the amount of insulin in the fetal
      bovine serum being sufficient for maximal stimulation of SREBP-1 expression.
      Third, we show that the increase in SREBP-1 protein is due to an increase in
      SREBP-1 mRNA. Reporter gene analysis of the SREBP-1c promoter demonstrated a
      glucose-dependent induction of transcription. In contrast, expression of a fixed
      amount of the precursor form of SREBP-1c protein showed that glucose does not
      influence its cleavage. Fourth, we demonstrate that the glucose induction of
      SREBP could not be reproduced by fructose, xylose, or galactose nor by glucose
      analogs 2-deoxy glucose and 3-O-methyl glucopyranose. These data provide strong
      evidence for the induction of SREBP-1c mRNA by glucose leading to increased
      mature protein in the nucleus, thus providing a potential mechanism for the up
      regulation of lipogenic genes by glucose in vivo.

PMID- 10913130
TI  - Membrane localization of Raf assists engagement of downstream effectors.
AB  - We have previously described a small molecule-directed protein dimerization
      strategy, using coumermycin to juxtapose Raf fusion proteins containing the
      coumermycin-binding domain GyrB. Oligomerization of cytoplasmically localized Raf
      GyrB fusion proteins leads to an increase in the kinase activity of both Raf and
      its substrate Mek. Surprisingly, more distal targets, such as Erk1 and Erk2, are
      not activated using this approach. Here we report that coumermycin-induced
      oligomerization of a membrane-localized Raf-GyrB fusion protein potently
      activated Erk1 and Erk2, up-regulated Fos protein levels, and induced expression
      of many immediate-early response genes. Thus, both membrane localization and
      oligomerization of Raf-GyrB are required to target Raf signals to downstream
      effectors. The ability to activate the entire Raf signal transduction cascade
      conditionally, using coumermycin-induced oligomerization, should prove useful for
      dissecting Raf-mediated effects on gene expression and cellular differentiation.

PMID- 10913131
TI  - Identification of an atypical Grb2 carboxyl-terminal SH3 domain binding site in
      Gab docking proteins reveals Grb2-dependent and -independent recruitment of Gab1
      to receptor tyrosine kinases.
AB  - The Gab family of docking proteins is phosphorylated in response to various
      growth factors and cytokines and serves to recruit multiple signaling proteins.
      Gab1 acts downstream from the Met-hepatocyte growth factor receptor, and Gab1
      overexpression promotes Met-dependent morphogenesis of epithelial cells.
      Recruitment of Gab1 to Met or epidermal growth factor (EGF) receptors requires a
      receptor-binding site for the Grb2 adapter protein and a proline-rich domain in
      Gab1, defined as the Met-binding domain. To determine the requirement for Grb2 in
      Gab1 recruitment, we have mapped two Grb2 carboxyl-terminal SH3 domain binding
      sites conserved in Gab1 and related protein Gab2. One corresponds to a canonical
      Grb2-binding motif, whereas the second, located within the Gab1 Met-binding
      domain, requires the proline and arginine residues of an atypical PXXXR motif.
      The PXXXR motif is required but not sufficient for Grb2 binding, whereas an
      extended motif, PX3RX2KPX7PLD, conserved in Gab proteins as well as the Grb2/Gads
      docking protein, Slp-76, efficiently competes binding of Grb2 or Gads adapter
      proteins. The association of Gab1 with Grb2 is required for Gab1 recruitment to
      the EGF receptor but not the Met receptor. Hence different mechanisms of Gab1
      recruitment may reflect the distinct biological functions for Gab1 downstream
      from the EGF and Met receptors.

PMID- 10913132
TI  - NF-kappa B inhibits glucocorticoid and cAMP-mediated expression of the
      phosphoenolpyruvate carboxykinase gene.
AB  - Transcription of the phosphoenolpyruvate carboxykinase (PEPCK) gene is regulated
      by a variety of agents. Glucocorticoids, retinoic acid, and glucagon (via its
      second messenger, cAMP) stimulate PEPCK gene transcription, whereas insulin,
      phorbol esters, cytokines, and oxidative stress have an opposing effect.
      Stimulation of PEPCK gene expression has been extensively studied, and a number
      of important DNA elements and binding proteins that regulate the transcription of
      this gene have been identified. However, the mechanisms utilized to turn off
      expression of this gene are not well-defined. Many of the negative regulators of
      PEPCK gene transcription also stimulate the nuclear localization and activation
      of the transcription factor NF-kappaB, so we hypothesized that this factor could
      be involved in the repression of PEPCK gene expression. We find that the p65
      subunit of NF-kappaB represses the increase of PEPCK gene transcription mediated
      by glucocorticoids and cAMP in a concentration-dependent manner. The mutation of
      an NF-kappaB binding element identified in the PEPCK gene promoter fails to
      abrogate this repression. Further analysis suggests that p65 represses PEPCK gene
      transcription through a protein.protein interaction with the coactivator, CREB
      binding protein.

PMID- 10913133
TI  - Permeation and activation of the M2 ion channel of influenza A virus.
AB  - The M(2) ion channel protein of influenza A virus is essential for mediating
      protein-protein dissociation during the virus uncoating process that occurs when
      the virus is in the acidic environment of the lumen of the secondary endosome.
      The difficulty of determining the ion selectivity of this minimalistic ion
      channel is due in part to the fact that the channel activity is so great that it
      causes local acidification in the expressing cells and a consequent alteration of
      reversal voltage, V(rev). We have confirmed the high proton selectivity of the
      channel (1.5-2.0 x 10(6)) in both oocytes and mammalian cells by using four
      methods as follows: 1) comparison of V(rev) with proton equilibrium potential; 2)
      measurement of pH(in) and V(rev) while Na(+)(out) was replaced; 3) measurements
      with limiting external buffer concentration to limit proton currents
      specifically; and 4) comparison of measurements of M(2)-expressing cells with
      cells exposed to a protonophore. Increased currents at low pH(out) are due to
      true activation and not merely increased [H(+)](out) because increased pH(out)
      stops the outward current of acidified cells. Although the proton conductance is
      the biologically relevant conductance in an influenza virus-infected cell,
      experiments employing methods 1-3 show that the channel is also capable of
      conducting NH(4)(+), probably by a different mechanism from H(+).

PMID- 10913134
TI  - Identification of a cysteine residue in the active site of nitroalkane oxidase by
      modification with N-ethylmaleimide.
AB  - The flavoprotein nitroalkane oxidase catalyzes the oxidative denitrification of
      primary or secondary nitroalkanes to the corresponding aldehydes or ketones with
      production of hydrogen peroxide and nitrite. The enzyme is irreversibly
      inactivated by treatment with N-ethylmaleimide at pH 7. The inactivation is time
      dependent and shows first-order kinetics for three half-lives. The second-order
      rate constant for inactivation is 3.4 +/- 0.06 m(-)(1) min(-)(1). The competitive
      inhibitor valerate protects the enzyme from inactivation, indicating an active
      site-directed modification. Comparison of tryptic maps of enzyme treated with N
      [ethyl-1-(14)C]maleimide in the absence and presence of valerate shows a single
      radioactive peptide differentially labeled in the unprotected enzyme. The
      sequence of this peptide was determined to be LLNEVMCYPLFDGGNIGLR using Edman
      degradation and matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry. The cysteine residue was identified as the site of alkylation by
      ion trap mass spectrometry.

PMID- 10913135
TI  - Vinblastine-induced phosphorylation of Bcl-2 and Bcl-XL is mediated by JNK and
      occurs in parallel with inactivation of the Raf-1/MEK/ERK cascade.
AB  - Microtubule-damaging agents arrest cells at G(2)/M and induce apoptosis in
      association with phosphorylation of the anti-apoptotic proteins Bcl-2 and Bcl
      X(L). Because microtubule inhibitors activate JNK, we sought to determine whether
      JNK was responsible for Bcl-2/Bcl-X(L) phosphorylation in KB-3 cells treated with
      vinblastine. Two major endogenous forms of JNK, p46(JNK1) and p54(JNK2), were
      present in KB-3 cells, and both isoforms were activated by vinblastine as
      determined by Mono Q chromatography. We used antisense oligonucleotides (AS) to
      specifically inhibit their expression. A combination of AS-JNK1 with AS-JNK2
      inhibited by 80% vinblastine-induced phosphorylation of two known JNK substrates,
      c-Jun and ATF-2. In addition, AS-JNK1/2 inhibited vinblastine-induced
      phosphorylation of Bcl-2 by 85% and that of Bcl-X(L) by 65%. Stable expression of
      the JNK scaffold protein JIP-1 blocked vinblastine-induced phosphorylation of c
      Jun and ATF-2, but did not affect Bcl-2/Bcl-X(L) phosphorylation, confirming a
      bifurcation in JNK signaling involving both nuclear and non-nuclear substrates.
      Vinblastine-induced phosphorylation of Raf-1 was unaffected by AS-JNK1/2 and was
      associated with loss of activity for MEK substrate in vitro and inactivation of
      ERK in vivo. These results provide evidence for a direct role of the JNK pathway
      in apoptotic regulation through Bcl-2/Bcl-X(L) phosphorylation.

PMID- 10913136
TI  - Defective uptake and utilization of long chain fatty acids in muscle and adipose
      tissues of CD36 knockout mice.
AB  - The transmembrane protein CD36 has been identified in isolated cell studies as a
      putative transporter of long chain fatty acids. In humans, an association between
      CD36 deficiency and defective myocardial uptake of the fatty acid analog 15-(p
      iodophenyl)-3-(R, S)-methyl pentadecanoic acid (BMIPP) has been reported. To
      determine whether this association represents a causal link and to assess the
      physiological role of CD36, we compared tissue uptake and metabolism of two
      iodinated fatty acid analogs BMIPP and 15-(p-iodophenyl) pentadecanoic acid
      (IPPA) in CD36 null and wild type mice. We also investigated the uptake and lipid
      incorporation of palmitate by adipocytes isolated from both groups. Compared with
      wild type, uptake of BMIPP and IPPA was reduced in heart (50-80%), skeletal
      muscle (40-75%), and adipose tissues (60-70%) of null mice. The reduction was
      associated with a 50-68% decrease in label incorporation into triglycerides and
      in 2-3-fold accumulation of label in diglycerides. Identical results were
      obtained from studies of [(3)H]palmitate uptake in isolated adipocytes. The block
      in diglyceride to triglyceride conversion could not be explained by changes in
      specific activities of the key enzymes long chain acyl-CoA synthetase and
      diacylglycerol acyltransferase, which were similar in tissues from wild type and
      null mice. It is concluded that CD36 facilitates a large fraction of fatty acid
      uptake by heart, skeletal muscle, and adipose tissues and that CD36 deficiency in
      humans is the cause of the reported defect in myocardial BMIPP uptake. In CD36
      expressing tissues, uptake regulates fatty acid esterification at the level of
      diacylglycerol acyltransferase by determining fatty acyl-CoA supply. The membrane
      transport step may represent an important control site for fatty acid metabolism
      in vivo.

PMID- 10913137
TI  - A microsomal GTPase is required for glycopeptide export from the mammalian
      endoplasmic reticulum.
AB  - Bidirectional transport of proteins via the Sec61p translocon across the
      endoplasmic reticulum (ER) membrane is a recognized component of the ER quality
      control machinery. Following translocation and engagement by the luminal quality
      control system, misfolded and unassembled proteins are exported from the ER lumen
      back to the cytosol for degradation by the proteasome. Additionally, other ER
      contents, including oligosaccharides, oligopeptides, and glycopeptides, are
      efficiently exported from mammalian and yeast systems, indicating that
      bidirectional transport across ER membranes is a general eukaryotic phenomenon.
      Glycopeptide and protein export from the ER in in vitro systems is both ATP- and
      cytosol-dependent. Using a well established system to study glycopeptide export
      and conventional liquid chromatography, we isolated a single polypeptide species
      of 23 kDa from rat liver cytosol that was capable of fully supporting
      glycopeptide export from rat microsomes in the presence of an ATP-regenerating
      system. The protein was identified by mass spectrometric sequence analysis as
      guanylate kinase (GK), a housekeeping enzyme critical in the regulation of
      cellular GTP levels. We confirmed the ability of GK to substitute for complete
      cytosol by reconstitution of glycopeptide export from rat liver microsomes using
      highly purified recombinant GK from Saccharomyces cerevisiae. Most significantly,
      we found that the GK (and hence the cytosolic component) requirement was fully
      bypassed by low micromolar concentrations of GDP or GTP. Similarly, export was
      inhibited by non-hydrolyzable analogues of GDP and GTP, indicating a requirement
      for GTP hydrolysis. Membrane integrity was fully maintained under assay
      conditions, as no ER luminal proteins were released. Competence for glycopeptide
      export was abolished by very mild protease treatment of microsomes, indicating
      the presence of an essential protein on the cytosolic face of the ER membrane.
      These data demonstrate that export of glycopeptide export is controlled by a
      microsomal GTPase and is independent of cytosolic protein factors.

PMID- 10913138
TI  - S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B
      protein in vivo.
AB  - In solution, S100B protein is a noncovalent homodimer composed of two subunits
      associated in an antiparallel manner. Upon calcium binding, the conformation of
      S100B changes dramatically, leading to the exposure of hydrophobic residues at
      the surface of S100B. The residues in the C-terminal domain of S100B encompassing
      Phe(87) and Phe(88) have been implicated in interaction with target proteins. In
      this study, we used two-hybrid technology to identify specific S100B target
      proteins. Using S100B as bait, we identify S100A6 and S100A11 as specific targets
      for S100B. S100A1, the closest homologue of S100B, is capable of interaction with
      S100B but does not interact with S100A6 or S100A11. S100B, S100A6, and S100A11
      isoforms are co-regulated and co-localized in astrocytoma U373 cells.
      Furthermore, co-immunoprecipitation experiments demonstrated that Ca(2+)/Zn(2+)
      stabilizes S100B-S100A6 and S100B-S100A11 heterocomplexes. Deletion of the C
      terminal domain or mutation of Phe(87) and Phe(88) residues has no effect on
      S100B homodimerization and heterodimerization with S100A1 but drastically
      decreases interaction between S100B and S100A6 or S100A11. Our data suggest that
      the interaction between S100B and S100A6 or S100A11 should not be viewed as a
      typical S100 heterodimerization but rather as a model of interaction between
      S100B and target proteins.

PMID- 10913139
TI  - Homophilic interaction of junctional adhesion molecule.
AB  - Junctional adhesion molecule (JAM) is an integral membrane protein that belongs
      to the immunoglobulin superfamily, localizes at tight junctions, and regulates
      both paracellular permeability and leukocyte transmigration. To investigate
      molecular determinants of JAM function, the extracellular domain of murine JAM
      was produced as a recombinant soluble protein (rsJAM) in insect cells. rsJAM
      consisted in large part of noncovalent homodimers, as assessed by analytical
      ultracentrifugation. JAM dimers were also detected at the surface of Chinese
      hamster ovary cells transfected with murine JAM, as evaluated by cross-linking
      and immunoprecipitation. Furthermore, fluid-phase rsJAM bound dose-dependently
      solid-phase rsJAM, and such homophilic binding was inhibited by anti-JAM Fab
      BV11, but not by Fab BV12. Interestingly, Fab BV11 exclusively bound rsJAM dimers
      (but not monomers) in solution, whereas Fab BV12 bound both dimers and monomers.
      Finally, we mapped the BV11 and BV12 epitopes to a largely overlapping sequence
      in proximity of the extracellular amino terminus of JAM. We hypothesize that
      rsJAM dimerization induces a BV11-positive conformation which in turn is critical
      for rsJAM homophilic interactions. Dimerization and homophilic binding may
      contribute to both adhesive function and junctional organization of JAM.

PMID- 10913140
TI  - Changing the donor cofactor of bovine alpha 1, 3-galactosyltransferase by fusion
      with UDP-galactose 4-epimerase. More efficient biocatalysis for synthesis of
      alpha-Gal epitopes.
AB  - Two fusion enzymes consisting of uridine diphosphogalactose 4-epimerase (UDP
      galactose 4-epimerase, EC ) and alpha1, 3-galactosyltransferase (EC ) with an N
      terminal His(6) tag and an intervening three-glycine linker were constructed by
      in-frame fusion of the Escherichia coli galE gene either to the 3' terminus (f1)
      or to the 5' terminus (f2) of a truncated bovine alpha1, 3-galactosyltransferase
      gene, respectively. Both fusion proteins were expressed in cell lysate as active,
      soluble forms as well as in inclusion bodies as improperly folded proteins. Both
      f1 and f2 were determined to be homodimers, based on a single band observed at
      about 67 kDa in SDS-polyacrylamide gel electrophoresis and on a single peak with
      a molecular mass around 140 kDa determined by gel filtration chromatography for
      each of the enzymes. Without altering the acceptor specificity of the
      transferase, the fusion with the epimerase changed the donor requirement of
      alpha1, 3-galactosyltransferase from UDP-galactose to UDP-glucose and decreased
      the cost for the synthesis of biomedically important Galalpha1,3Gal-terminated
      oligosaccharides by more than 40-fold. For enzymatic synthesis of
      Galalpha1,3Galbeta1,4Glc from UDP-glucose and lactose, the genetically fused
      enzymes f1 and f2 exhibited kinetic advantages with overall reaction rates that
      were 300 and 50%, respectively, higher than that of the system containing equal
      amounts of epimerase and galactosyltransferase. These results indicated that the
      active sites of the epimerase and the transferase in fusion enzymes were in
      proximity. The kinetic parameters suggested a random mechanism for the substrate
      binding of the alpha1, 3-galactosyltransferase. This work demonstrated a general
      approach that fusion of a glycosyltransferase with an epimerase can change the
      required but expensive sugar nucleotide to a less expensive one.

PMID- 10913141
TI  - Interaction of mannose-binding protein with associated serine proteases: effects
      of naturally occurring mutations.
AB  - Mannose-binding protein (MBP; mannose-binding lectin) forms part of the innate
      immune system. By binding directly to carbohydrates on the surfaces of potential
      microbial pathogens, MBP and MBP-associated serine proteases (MASPs) can replace
      antibodies and complement components C1q, C1r, and C1s of the classical
      complement pathway. In order to investigate the mechanisms of MASP activation by
      MBP, the cDNAs of rat MASP-1 and -2 have been isolated, and portions encompassing
      the N-terminal CUB and epidermal growth factor-like domains have been expressed
      and purified. Biophysical characterization of the purified proteins indicates
      that each truncated MASP is a Ca(2+)-independent homodimer in solution, in which
      the interacting modules include the N-terminal two domains. Binding studies
      reveal that both MASPs associate independently with rat MBP in a Ca(2+)-dependent
      manner through interactions involving the N-terminal three domains. The
      biophysical properties of the truncated MASPs indicate that the interactions with
      MBP leading to complement activation differ significantly from those between
      components C1q, C1r, and C1s of the classical pathway. Analysis of MASP binding
      by rat MBP containing naturally occurring mutations equivalent to those
      associated with human immunodeficiency indicates that binding to both truncated
      MASP-1 and MASP-2 proteins is defective in such mutants.

PMID- 10913142
TI  - Cloning of a gene for an acyl-CoA dehydrogenase from Pisum sativum L. and
      purification and characterization of its product as an isovaleryl-CoA
      dehydrogenase.
AB  - Isovaleryl-CoA dehydrogenase (IVD, EC ) catalyzes the third step in the
      catabolism of leucine in mammals. Deficiency of this enzyme leads to the clinical
      disorder isovaleric acidemia. IVD has been purified and characterized from human
      and rat liver, and the x-ray crystallographic structure of purified recombinant
      human IVD has been reported. Nothing is known about IVD activity in plants,
      although cDNA clones from Arabidopsis thaliana and partial sequences from
      Gossypium hirsutum and Oryza sativa have been identified as putative IVDs based
      on sequence homology and immuno cross-reactivity. In this report we describe the
      identification and characterization of an IVD from pea, purification of the
      enzyme using a novel and rapid auxin affinity chromatography matrix, and cloning
      of the corresponding gene. At the amino acid level, pea IVD is 60% similar to
      human and rat IVD. The specific activity and abundance of plant IVD was found to
      be significantly lower than for its human counterpart and exhibits developmental
      regulation. Substrate specificity of the plant enzyme is similar to the human
      IVD, and it cross-reacts to anti-human IVD antibodies. Molecular modeling of the
      pea enzyme based on the structure of human IVD indicates a high degree of
      structural similarity among these enzymes. Glu-244, shown to function as the
      catalytic base in human IVD along with most of the amino acids that make up the
      acyl CoA binding pocket, is conserved in pea IVD. The genomic structure of the
      plant IVD gene consists of 13 exons and 12 introns, spanning approximately 4
      kilobases, and the predicted RNA splicing sites exhibit the extended consensus
      sequence described for other plant genes.

PMID- 10913143
TI  - A bovine adrenocortical Kv1.4 K(+) channel whose expression is potently inhibited
      by ACTH.
AB  - We have cloned a bovine adrenal cortical (bKv1.4) K(+) channel cDNA whose
      expression is rapidly inhibited by adrenocorticotropic hormone (ACTH). The 4386
      nucleotide cDNA is homologous to other voltage-gated, rapidly inactivating Kv1.4
      channels, and includes a 1986-nucleotide coding region and large 5'- and 3'
      untranslated regions. Bovine Kv1.4-specific mRNA from adrenal zona fasciculata
      (AZF) cells was rapidly and potently reduced by ACTH, with a t(12) of
      approximately 1 h and an IC(50) of 1.2 pm. The membrane-permeable cAMP analog 8
      pcpt-cAMP also reduced bKv1.4 mRNA expression with kinetics similar to that
      observed with ACTH. Reduction of bKv1.4 mRNA expression by ACTH and 8-pcpt-cAMP
      was only partially inhibited by the selective protein kinase A antagonist H-89.
      Consistent with their effect on bKv1.4 mRNA, ACTH and 8-pcpt-cAMP both
      dramatically reduced the expression of bKv1.4-associated A-type current measured
      over 72 h. These results demonstrate that bovine AZF cells synthesize a Kv1.4
      type channel whose expression is inhibited at the pretranslational level by ACTH
      and 8-pcpt-cAMP by a mechanism that is partially dependent on the activation of
      protein kinase A. The rapid, potent reduction of bKv1.4 mRNA produced by ACTH and
      8-pcpt-cAMP indicates that the expression of this K(+) channel is under tonic
      inhibitory control of the hypothalamic-pituitary-adrenal axis. The basic
      electrical properties of AZF cells might be tightly regulated at the
      transcriptional level by the normal diurnal pattern of ACTH secretion, and
      altered during bouts of stress by the enhanced release of this pituitary peptide.
      Under conditions of prolonged stress or adrenal insufficiency, persistent ACTH
      induced changes in the electrical properties of AZF cells could be coupled to
      parallel changes in cortisol secretion.

PMID- 10913144
TI  - MioC is an FMN-binding protein that is essential for Escherichia coli biotin
      synthase activity in vitro.
AB  - Biotin synthase is required for the conversion of dethiobiotin to biotin and
      requires a number of accessory proteins and small molecule cofactors for activity
      in vitro. We have previously identified two of these proteins as flavodoxin and
      ferredoxin (flavodoxin) NADP(+) reductase. We now report the identification of
      MioC as a third essential protein, together with its cloning, purification, and
      characterization. Purified MioC has a UV-visible spectrum characteristic of a
      flavoprotein and contains flavin mononucleotide. The presence of flavin
      mononucleotide and the primary sequence similarity to flavodoxin suggest that
      MioC may function as an electron transport protein. The role of MioC in the
      biotin synthase reaction is discussed, and the structure and function of MioC is
      compared with that of flavodoxin.

PMID- 10913145
TI  - Tumor necrosis factor-induced microtubule stabilization mediated by
      hyperphosphorylated oncoprotein 18 promotes cell death.
AB  - Tumor necrosis factor (TNF)-induced cell death in the fibrosarcoma cell line L929
      occurs independently of caspase activation and cytochrome c release. However, it
      is dependent on mitochondria and is characterized by increased production of
      reactive oxygen intermediates that are essential to the death process. To
      identify signaling molecules involved in this TNF-induced, reactive oxygen
      intermediate-dependent cell death pathway, we performed a comparative study by
      two-dimensional gel electrophoresis of phosphoproteins from a mitochondria
      enriched fraction derived from TNF-treated and control cells. TNF induced rapid
      and persistent phosphorylation of the phosphorylation-responsive regulator of the
      microtubule (MT) dynamics, oncoprotein 18 (Op18). By using induced overexpression
      of wild type Op18 and phosphorylation site-deficient mutants S25A/S38A and
      S16A/S63A in L929 cells, we show that TNF-induced phosphorylation on each of the
      four Ser residues of Op18 promotes cell death and that Ser(16) and Ser(63) are
      the primary sites. This hyperphosphorylation of Op18 is known to completely turn
      off its MT-destabilizing activity. As a result, TNF treatment of L929 cells
      induced elongated and extremely tangled microtubules. These TNF-induced changes
      to the MT network were also observed in cells overexpressing wild type Op18 and,
      to a lesser extent, in cells overexpressing the S25A/S38A mutant. No changes in
      the MT network were observed upon TNF treatment of cells overexpressing the
      S16A/S63A mutant, and these cells were desensitized to TNF-induced cell death.
      These findings indicate that TNF-induced MT stabilization is mediated by
      hyperphosphorylation of Op18 and that this promotes cell death. The data suggest
      that Op18 and the MT network play a functional role in transduction of the cell
      death signal to the mitochondria.

PMID- 10913146
TI  - Role of endoproteolytic processing in the adhesive and signaling functions of
      alphavbeta5 integrin.
AB  - Some integrin alpha subunits undergo a post-translational cleavage in their
      extracellular domain. However, the role of this cleavage in integrin function is
      unclear. Enzymes involved in this maturation belong to the subtilisin-like
      endoprotease family (convertases). To understand the role of the alpha subunit
      cleavage in integrin function, we have designed stable transfectants (PDX39P
      cells) expressing alpha(1)-PDX, a convertase inhibitor. Immunoprecipitation of
      cell surface proteins from PDX39P showed that alpha(3), alpha(6) and alpha(v)
      integrins lack endoproteolytic cleavage. We have compared adhesion between PDX39P
      cells and mock-transfected cells on different extracellular matrix proteins. No
      difference in adhesion could be observed on laminin-1 and type I collagen, while
      attachment of PDX39P cells to vitronectin (ligand of the alpha(v)beta(5)
      integrin) was dramatically reduced. The reduced adhesion of PDX39P cells was not
      due to changes in integrin affinity as determined by solid-phase receptor assay
      in a cell-free environment. Intracellular signaling pathways activated by
      alpha(v) integrin ligation were also affected in PDX39P cells. It thus seems that
      the absence of endoproteolytic cleavage of alpha(v) integrins has important
      consequences on signal transduction pathways leading to alterations in integrin
      function such as cell adhesion.

PMID- 10913147
TI  - Regulation of phosphoenolpyruvate carboxykinase and insulin-like growth factor
      binding protein-1 gene expression by insulin. The role of winged helix/forkhead
      proteins.
AB  - Winged helix/forkhead (Fox) transcription factors have been implicated in the
      regulation of a number of insulin-responsive genes. The insulin response elements
      (IREs) of the phosphoenolpyruvate carboxykinase (PEPCK) and insulin-like growth
      factor-binding protein-1 (IGFBP-1) genes bind members of the FKHR and HNF3
      subclasses of Fox proteins. Previous mutational analyses of the PEPCK and IGFBP-1
      IREs revealed mutations which do not affect the binding of HNF3 proteins to these
      elements but do eliminate the ability of the IREs to mediate an insulin response.
      This dissociation of binding and function provided compelling evidence that HNF3
      proteins, per se, are not insulin response proteins. The same approach was used
      here to determine if FKHRL1, a member of the FKHR subclass of Fox proteins, binds
      to the PEPCK and IGFBP-1 IREs in a manner that correlates with the ability of
      these elements to mediate an insulin response. Overexpression of FKHRL1
      stimulates transcription from transfected reporter constructs that contain a
      multimerized PEPCK IRE or an IGFBP-1 IRE and this stimulation is repressed by
      insulin. There is a direct correlation between the ability of mutant versions of
      the PEPCK and IGFBP-1 IREs to bind FKHRL1 and their ability to mediate FKHRL1
      induced transcription when FKHRL1 is overexpressed. However, under conditions
      where FKHRL1 is not overexpressed, there is a lack of correlation between FKHRL1
      binding to mutant versions of the PEPCK and IGFBP-1 IREs and the ability of these
      elements to mediate an insulin response. Therefore, the PEPCK and IGFBP-1 IREs
      mediate FKHRL1-induced transcription and its inhibition by insulin when this
      protein is overexpressed, but at the normal cellular concentration of FKHRL1 the
      insulin response mediated by these elements must involve another protein.

PMID- 10913148
TI  - The conformation of the T-antigen disaccharide bound to Maclura pomifera
      agglutinin in aqueous solution.
AB  - The complex of Maclura pomifera agglutinin with the T-antigen disaccharide (beta
      d-Gal-(1-->3)-alpha-d-GalNAc-(1-->O)-Me) was investigated by NMR spectroscopy in
      aqueous solution. Intramolecular transferred nuclear Overhauser enhancement (NOE)
      effects between the monosaccharide moieties were used to derive the ligand
      conformation in the lectin-bound state. Ligand protons in contact with the
      protein were identified by saturation transfer difference experiments and
      intermolecular transferred NOE effects. It is demonstrated that structural
      differences exist for the ligand-lectin complex in aqueous solution as compared
      with the previously published crystal structure (Lee, X., Thompson, A., Zhiming,
      Z., Ton-that, H., Biesterfeldt, J., Ogata, C., Xu, L., Johnston, R. A. Z. , and
      Young, N. M. (1998) J. Biol. Chem. 273, 6312-6318). In order to accommodate the O
      methyl group of the disaccharide, the amino acid side chain of Tyr-122 has to
      rotate from its position in the crystal. The NMR data are in accord with two
      conformational families at the beta-(1-->3)glycosidic linkage in the solution
      complex with interglycosidic angles phi/psi = 45/-65 degrees and -65/-18 degrees.
      These differ from the bound conformation of the ligand in the crystal (phi/psi =
      39/-8 degrees ) and are not highly populated by the ligand in the free state. The
      reason for the structural differences at the beta-(1-->3)glycosidic linkage are
      hydrogen bonds that stabilize the relative orientation of the monosaccharide
      units in the crystal. Our results demonstrate that the crystallization of a
      protein-carbohydrate complex can interfere with the delicate process of
      carbohydrate recognition in solution.

PMID- 10913149
TI  - Identification of subunits a, b, and c1 from Acetobacterium woodii Na+-F1F0
      ATPase. Subunits c1, c2, AND c3 constitute a mixed c-oligomer.
AB  - The Na(+)-F(1)F(0)-ATPase operon of Acetobacterium woodii was recently shown to
      contain, among eleven atp genes, those genes that encode subunit a and b, a gene
      encoding a 16-kDa proteolipid (subunit c(1)), and two genes encoding 8-kDa
      proteolipids (subunits c(2) and c(3)). Because subunits a, b, and c(1) were not
      found in previous enzyme preparations, we re-determined the subunit composition
      of the enzyme. The genes were overproduced, and specific antibodies were raised.
      Western blots revealed that subunits a, b, and c(1) are produced and localized in
      the cytoplasmic membrane. Membrane protein complexes were solubilized by
      dodecylmaltoside and separated by blue native-polyacrylamide gel electrophoresis,
      and the ATPase subunits were resolved by SDS-polyacrylamide gel electrophoresis.
      N-terminal sequence analyses revealed the presence of subunits a, c(2), c(3), b,
      delta, alpha, gamma, beta, and epsilon. Biochemical and immunological analyses
      revealed that subunits c(1), c(2), and c(3) are all part of the c-oligomer, the
      first of a F(1)F(0)-ATPase that contains 8- and 16-kDa proteolipids.

PMID- 10913150
TI  - Identification of the melatonin-binding site MT3 as the quinone reductase 2.
AB  - The regulation of the circadian rhythm is relayed from the central nervous system
      to the periphery by melatonin, a hormone synthesized at night in the pineal
      gland. Besides two melatonin G-coupled receptors, mt(1) and MT(2), the existence
      of a novel putative melatonin receptor, MT(3), was hypothesized from the
      observation of a binding site in both central and peripheral hamster tissues with
      an original binding profile and a very rapid kinetics of ligand exchange compared
      with mt(1) and MT(2). In this report, we present the purification of MT(3) from
      Syrian hamster kidney and its identification as the hamster homologue of the
      human quinone reductase 2 (QR(2), EC ). Our purification strategy included the
      use of an affinity chromatography step which was crucial in purifying MT(3) to
      homogeneity. The protein was sequenced by tandem mass spectrometry and shown to
      align with 95% identity with human QR(2). After transfection of CHO-K1 cells with
      the human QR(2) gene, not only did the QR(2) enzymatic activity appear, but also
      the melatonin-binding sites with MT(3) characteristics, both being below the
      limit of detection in the native cells. We further confronted inhibition data
      from MT(3) binding and QR(2) enzymatic activity obtained from samples of Syrian
      hamster kidney or QR(2)-overexpressing Chinese hamster ovary cells, and observed
      an overall good correlation of the data. In summary, our results provide the
      identification of the melatonin-binding site MT(3) as the quinone reductase QR(2)
      and open perspectives as to the function of this enzyme, known so far mainly for
      its detoxifying properties.

PMID- 10913151
TI  - Glucose-stimulated insulin biosynthesis depends on insulin-stimulated insulin
      gene transcription.
AB  - Glucose stimulation of pancreatic beta-cells leads to insulin secretion as well
      as up-regulation of insulin biosynthesis. The acute elevation in pro-insulin
      levels is thought to be exclusively because of the activation of translation of
      pre-existing prepro-insulin mRNA. Glucose-stimulated insulin gene transcription
      is believed to be a long term effect and should therefore not contribute to the
      acute elevation in pro-insulin levels. We have recently shown that glucose
      activates insulin gene transcription within minutes and that secreted insulin is
      one of the key factors triggering this process in an autocrine manner. We now
      provide evidence that 50% of the glucose-stimulated, acute pro-insulin
      biosynthesis within 30 min results from up-regulated insulin gene transcription.
      Our data led us to propose that glucose elevates pro-insulin levels by
      stimulating both transcriptional and post-transcriptional/post-translational
      events to an equal extent. Whereas the stimulatory effect on transcription is
      mediated by insulin secreted in response to glucose, glucose directly stimulates
      the post-transcriptional/post-translational processes.

PMID- 10913152
TI  - Synthetic zinc finger transcription factor action at an endogenous chromosomal
      site. Activation of the human erythropoietin gene.
AB  - We have targeted the activation of an endogenous chromosomal locus including the
      human erythropoietin gene using synthetic transcription factors. These
      transcription factors are targeted to particular DNA sequences in the 5'-flanking
      region of the erythropoietin gene through engineering of a zinc finger DNA
      binding domain. The DNA binding domain is linked to a VP16 transcriptional
      activation domain. We find that these synthetic transcription factors invariably
      activate transiently transfected templates in which sequences within the 5' flank
      of the erythropoietin gene are fused to a luciferase reporter. The efficiency of
      activation under these circumstances at a defined site is dependent on DNA
      binding affinity. In contrast, only a subset of these same zinc finger proteins
      is able to activate the endogenous chromosomal locus. The activity of these
      proteins is influenced by their capacity to gain access to their recognition
      elements within the chromatin infrastructure. Zinc finger transcription factors
      will provide a powerful tool to probe the determinants of chromatin accessibility
      and remodeling within endogenous chromosomal loci.

PMID- 10913153
TI  - Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt
      signaling.
AB  - Glycogen synthase kinase 3beta (GSK3beta) is a key component in many biological
      processes including insulin and Wnt signaling. Since the activation of each
      signaling pathway results in a decrease in GSK3beta activity, we examined the
      specificity of their downstream effects in the same cell type. Insulin induces an
      increased activity of glycogen synthase but has no influence on the protein level
      of beta-catenin. In contrast, Wnt increases the cytosolic pool of beta-catenin
      but not glycogen synthase activity. We found that, unlike insulin, neither the
      phosphorylation status of the serine9 residue of GSK3beta nor the activity of
      protein kinase B is regulated by Wnt. Although the decrease in GSK3beta activity
      is required, GSK3beta may not be the limiting component for Wnt signaling in the
      cells that we examined. Our results suggest that the axin-conductin complexed
      GSK3beta may be dedicated to Wnt rather than insulin signaling. Insulin and Wnt
      pathways regulate GSK3beta through different mechanisms, and therefore lead to
      distinct downstream events.

PMID- 10913154
TI  - p21 inhibits Thr161 phosphorylation of Cdc2 to enforce the G2 DNA damage
      checkpoint.
AB  - The cyclin-dependent kinase inhibitor p21 is required for a sustained G(2) arrest
      after activation of the DNA damage checkpoint. Here we have addressed the
      mechanism by which p21 can contribute to this arrest in G(2). We show that p21
      blocks the activating phosphorylation of Cdc2 on Thr(161). p21 does not interfere
      with the dephosphorylation of two inhibitory phosphorylation sites on Cdc2,
      Thr(14) and Tyr(15), indicating that p21 targets a different event in Cdc2
      activation as the well described DNA damage checkpoint pathway involving Chk1 and
      Cdc25C. Taken together our data show that a cell is equipped with at least two
      independent pathways to ensure efficient inhibition of Cdc2 activity in response
      to DNA damage, influencing both positive and negative regulatory phosphorylation
      events on Cdc2.

PMID- 10913155
TI  - Sustained down-regulation of the epidermal growth factor receptor by decorin. A
      mechanism for controlling tumor growth in vivo.
AB  - The small leucine-rich proteoglycan decorin interacts with the epidermal growth
      factor receptor (EGFR) and triggers a signaling cascade that leads to elevation
      of endogenous p21 and growth suppression. We demonstrate that decorin causes a
      sustained down-regulation of the EGFR. Upon stable expression of decorin, the
      EGFR number is reduced by approximately 40%, without changes in EGFR expression.
      However, EGFR phosphorylation is nearly completely abolished. Concurrently,
      decorin attenuates the EGFR-mediated mobilization of intracellular calcium and
      blocks the growth of tumor xenografts by down-regulating the EGFR kinase in vivo.
      Thus, decorin acts as an autocrine and paracrine regulator of tumor growth and
      could be utilized as an effective anti-cancer agent.

PMID- 10913156
TI  - Anandamide induces apoptosis in human cells via vanilloid receptors. Evidence for
      a protective role of cannabinoid receptors.
AB  - The endocannabinoid anandamide (AEA) is shown to induce apoptotic bodies
      formation and DNA fragmentation, hallmarks of programmed cell death, in human
      neuroblastoma CHP100 and lymphoma U937 cells. RNA and protein synthesis
      inhibitors like actinomycin D and cycloheximide reduced to one-fifth the number
      of apoptotic bodies induced by AEA, whereas the AEA transporter inhibitor AM404
      or the AEA hydrolase inhibitor ATFMK significantly increased the number of dying
      cells. Furthermore, specific antagonists of cannabinoid or vanilloid receptors
      potentiated or inhibited cell death induced by AEA, respectively. Other
      endocannabinoids such as 2-arachidonoylglycerol, linoleoylethanolamide,
      oleoylethanolamide, and palmitoylethanolamide did not promote cell death under
      the same experimental conditions. The formation of apoptotic bodies induced by
      AEA was paralleled by increases in intracellular calcium (3-fold over the
      controls), mitochondrial uncoupling (6-fold), and cytochrome c release (3-fold).
      The intracellular calcium chelator EGTA-AM reduced the number of apoptotic bodies
      to 40% of the controls, and electrotransferred anti-cytochrome c monoclonal
      antibodies fully prevented apoptosis induced by AEA. Moreover, 5-lipoxygenase
      inhibitors 5,8,11,14-eicosatetraynoic acid and MK886, cyclooxygenase inhibitor
      indomethacin, caspase-3 and caspase-9 inhibitors Z-DEVD-FMK and Z-LEHD-FMK, but
      not nitric oxide synthase inhibitor Nomega-nitro-l-arginine methyl ester,
      significantly reduced the cell death-inducing effect of AEA. The data presented
      indicate a protective role of cannabinoid receptors against apoptosis induced by
      AEA via vanilloid receptors.

PMID- 10913157
TI  - Human colorectal cancers express a constitutively active cholecystokinin
      B/gastrin receptor that stimulates cell growth.
AB  - Although ectopic expression of the cholecystokinin B/gastrin receptor (CCK-BR) is
      widely reported in human colorectal cancers, its role in mediating the
      proliferative effects of gastrin1-17 (G-17) on these cancers is unknown. Here we
      report the isolation of a novel splice variant of CCK-BR that exhibits
      constitutive (ligand-independent) activation of pathways regulating intracellular
      free Ca(2+) ([Ca(2+)](i)) and cell growth. The splice variant (designated CCK
      BRi4sv for intron 4-containing splice variant) is expressed in colorectal cancers
      but not in normal colonic mucosa adjacent to the cancer. Balb3T3 cells expressing
      CCK-BRi4sv exhibited spontaneous, ligand-independent, oscillatory increases in
      [Ca(2+)](i), whereas cells expressing wild-type CCK-BR did not. Primary cultures
      of cells isolated from resected colorectal cancers also exhibited a similar
      pattern of spontaneous [Ca(2+)](i) oscillations. For both Balb3T3 and primary
      tumor cells, application of G-17 (10 and 200 nm, respectively) caused an increase
      in [Ca(2+)](i). Selective CCK-BR antagonists blocked the G-17-stimulated Ca(2+)
      responses but not the spontaneous [Ca(2+)](i) oscillations. Cells expressing CCK
      BRi4sv exhibited an increased growth rate ( approximately 2.5-fold), in the
      absence of G-17, compared with cells expressing wild-type CCK-BR. The selective
      pattern of expression, constitutive activity, and trophic action associated with
      CCK-BRi4sv suggest that this variant may regulate colorectal cancer cell
      proliferation though a gastrin-independent mechanism.

PMID- 10913158
TI  - Characterization of a sulfur-regulated oxygenative alkylsulfatase from
      Pseudomonas putida S-313.
AB  - The atsK gene of Pseudomonas putida S-313 was required for growth with alkyl
      sulfate esters as sulfur source. The AtsK protein was overexpressed in
      Escherichia coli and purified to homogeneity. Sequence analysis revealed that
      AtsK was closely related to E. coli taurine dioxygenase (38% amino acid
      identity). The AtsK protein catalyzed the alpha-ketoglutarate-dependent cleavage
      of a range of alkyl sulfate esters, with chain lengths ranging from C(4) to
      C(12), required oxygen and Fe(2+) for activity and released succinate, sulfate,
      and the corresponding aldehyde as products. Enzyme activity was optimal at pH 7
      and was strongly stimulated by ascorbate. Unlike most other characterized alpha
      ketoglutarate-dependent dioxygenases, AtsK accepted a range of alpha-keto acids
      as co-substrates, including alpha-ketoglutarate (K(m) 140 microm), alpha
      ketoadipate, alpha-ketovalerate, and alpha-ketooctanoate. The measured K(m)
      values for hexyl sulfate and SDS were 40 and 34 microm, respectively. The
      apparent M(r) of the purified enzyme of 121,000 was consistent with a
      homotetrameric structure, which is unusual for this enzyme superfamily, members
      of which are usually monomeric or dimeric. The properties and amino acid sequence
      of the AtsK enzyme thus define it as an unusual oxygenolytic alkylsulfatase and a
      novel member of the alpha-ketoglutarate-dependent dioxygenase family.

PMID- 10913159
TI  - In vivo interaction of the adapter protein CD2-associated protein with the type 2
      polycystic kidney disease protein, polycystin-2.
AB  - We identified a developmentally regulated gene from mouse kidney whose expression
      is up-regulated in metanephrogenic mesenchyme cells when they are induced to
      differentiate to epithelial cells during kidney organogenesis. The deduced 70.5
      kDa protein, originally named METS-1 (mesenchyme-to-epithelium transition protein
      with SH3 domains), has since been cloned as a CD2-associated protein (CD2AP).
      CD2AP is strongly expressed in glomerular podocytes, and the absence of CD2AP in
      mice results in congenital nephrotic syndrome. We have found that METS-1/CD2AP
      (hereafter referred to as CD2AP) is expressed at lower levels in renal tubular
      epithelial cells in the adult kidney, particularly in distal nephron segments.
      Independent yeast two-hybrid screens using the COOH-terminal region of either
      CD2AP or polycystin-2 as bait identified the COOH termini of polycystin-2 and
      CD2AP, respectively, as strong interacting partners. This interaction was
      confirmed in cultured cells by co-immunoprecipitation of endogenous polycystin-2
      with endogenous CD2AP and vice versa. CD2AP shows a diffuse reticular cytoplasmic
      and perinuclear pattern of distribution, similar to polycystin-2, in cultured
      cells, and the two proteins co-localize by indirect double immunofluorescence
      microscopy. CD2AP is an adapter molecule that associates with a variety of
      membrane proteins to organize the cytoskeleton around a polarized site. Such a
      function fits well with that hypothesized for the polycystin proteins in renal
      tubular epithelial cells, and the present findings suggest that CD2AP has a role
      in polycystin-2 function.

PMID- 10913160
TI  - Activation of host cell phosphatidylinositol 3-kinases by Trypanosoma cruzi
      infection.
AB  - Trypanosoma cruzi, the causative agent of Chagas' disease in humans, is an
      intracellular protozoan parasite with the ability to invade a wide variety of
      mammalian cells by a unique and remarkable process in cell biology that is poorly
      understood. Here we present evidence suggesting a role for the host
      phosphatidylinositol (PI) 3-kinases during T. cruzi invasion. The PI 3-kinase
      inhibitor wortmannin marked inhibited T. cruzi infection when macrophages were
      pretreated for 20 min at 37 degrees C before inoculation. Infection of
      macrophages with T. cruzi markedly stimulated the formation of the lipid products
      of the phosphatidylinositol (PI) 3-kinases, PI 3-phospate, PI 3,4-biphosphate,
      and PI 3,4,5-triphosphate, but not PI 4-phosphate or PI 4,5-biphosphate. This
      activation was inhibited by wortmannin. Infection with T. cruzi also stimulated a
      marked increase in the in vitro lipid kinase activities that are present in the
      immunoprecipitates of anti-p85 subunit of class I PI 3-kinase and anti
      phosphotyrosine. In addition, T. cruzi invasion also activated lipid kinase
      activity found in immunoprecipitates of class II and class III PI 3-kinases.
      These data demonstrate that T. cruzi invasion into macrophages strongly activates
      separated PI 3-kinase isoforms. Furthermore, the inhibition of the class I and
      class III PI 3-kinase activities abolishes the parasite entry into macrophages.
      These findings suggest a prominent role for the host PI 3-kinase activities
      during the T. cruzi infection process.

PMID- 10913161
TI  - Heat shock protein 90 mediates protein-protein interactions between human
      aminoacyl-tRNA synthetases.
AB  - Heat shock protein 90 (hsp90) is a molecular chaperone responsible for protein
      folding and maturation in vivo. Interaction of hsp90 with human glutamyl-prolyl
      tRNA synthetase (EPRS) was found by genetic screening, co-immunoprecipitation,
      and in vitro binding experiments. This interaction was sensitive to the hsp90
      inhibitor, geldanamycin, and also ATP, suggesting that the chaperone activity of
      hsp90 is required for interaction with EPRS. Interaction of EPRS with hsp90 was
      targeted to the region of three tandem repeats linking the two catalytic domains
      of EPRS that is also responsible for the interaction with isoleucyl-tRNA
      synthetase (IRS). Interaction of EPRS and IRS also depended on the activity of
      hsp90, implying that their association was mediated by hsp90. EPRS and IRS form a
      macromolecular protein complex with at least six other tRNA synthetases and three
      cofactors. hsp90 preferentially binds to most of the complex-forming enzymes
      rather than those that are not found in the complex. In addition, inactivation of
      hsp90 interfered with the in vivo incorporation of the nascent aminoacyl-tRNA
      synthetases into the multi-ARS complex. Thus, hsp90 appears to mediate protein
      protein interactions of mammalian tRNA synthetases.

PMID- 10913162
TI  - Role for homodimerization in growth deregulation by E2a fusion proteins.
AB  - The oncogenic transcription factor E2a-Pbx1 is expressed in some cases of acute
      lymphoblastic leukemia as a result of chromosomal translocation 1;19. The early
      observation that E2a-Pbx1 incorporates transcriptional activation domains from
      E2a and a DNA-binding homeodomain from Pbx1 inspired a model in which E2a-Pbx1
      promotes leukemogenic transformation of lymphoid progenitor cells through
      transcriptional induction of target genes defined by the Pbx1 portion of the
      molecule. However, the subsequent demonstration that the only known DNA-binding
      module on the molecule, the Pbx1 homeodomain, is dispensable for the induction of
      lymphoblastic lymphoma in transgenic mice called into question the contribution
      made by the Pbx1 portion. In this study, we have used a domain swap approach
      coupled with a fibroblast-based focus formation assay to evaluate further the
      requirement for PBX1-encoded peptide elements in growth deregulation by E2a-Pbx1.
      No impairment of focus formation was observed when the entire Pbx1 portion was
      replaced with DNA-binding/dimerization domains derived from yeast transcription
      factor GAL4 or GCN4. Furthermore, replacement of Pbx1 with tandem FKBP domains
      that mediate homodimerization in the presence of a synthetic ligand led to
      striking growth deregulation exclusively in the presence of the dimerizing agent.
      N-terminal elements encoded by E2A, including the AD1 transcriptional activation
      domain, were required for dimerization-induced focus formation. We conclude that
      transcriptional target genes defined by heterologous C-terminal DNA-binding
      modules are not required in growth deregulation by E2a fusion proteins. We
      speculate that interactions between N-terminal E2a elements and undefined
      proteins that could function as components of a transcriptional coactivator
      complex may be more important.

PMID- 10913163
TI  - Target gene specificity of E2F and pocket protein family members in living cells.
AB  - E2F-mediated transcription is thought to involve binding of an E2F-pocket protein
      complex to promoters in the G(0) phase of the cell cycle and release of the
      pocket protein in late G(1), followed by release of E2F in S phase. We have
      tested this model by monitoring protein-DNA interactions in living cells using a
      formaldehyde cross-linking and immunoprecipitation assay. We find that E2F target
      genes are bound by distinct E2F-pocket protein complexes which change as cells
      progress through the cell cycle. We also find that certain E2F target gene
      promoters are bound by pocket proteins when such promoters are transcriptionally
      active. Our data indicate that the current model applies only to certain E2F
      target genes and suggest that Rb family members may regulate transcription in
      both G(0) and S phases. Finally, we find that a given promoter can be bound by
      one of several different E2F-pocket protein complexes at a given time in the cell
      cycle, suggesting that cell cycle-regulated transcription is a stochastic, not a
      predetermined, process.

PMID- 10913164
TI  - Identification of a methylation imprint mark within the mouse Gnas locus.
AB  - The imprinted mouse gene Gnas produces the G protein alpha-subunit G(S)alpha and
      several other gene products by using alternative promoters and first exons.
      G(S)alpha is maternally expressed in some tissues and biallelically expressed in
      most other tissues, while the gene products NESP55 and XLalphas are maternally
      and paternally expressed, respectively. We investigated the mechanisms of Gnas
      imprinting. The G(S)alpha promoter and first exon are not methylated on either
      allele. A further upstream region (approximately from positions -3400 to -939
      relative to the G(S)alpha translational start site) is methylated only on the
      maternal allele in all adult somatic tissues and in early postimplantation
      development. Within this region lies a fourth promoter and first exon (exon 1A)
      that generates paternal-specific mRNAs of unknown function. Exon 1A and G(S)alpha
      mRNAs have similar expression patterns, making competition between their
      promoters unlikely. Differential methylation in this region is established during
      gametogenesis, being present in oocytes and absent in spermatozoa, and is
      maintained in preimplantation E3. 5d blastocysts. Therefore, this region is a
      methylation imprint mark. In contrast, differential methylation of the NESP55 and
      XLalphas promoter regions (Nesp and Gnasxl) is not established during
      gametogenesis. The methylation imprint mark that we identified may be important
      for the tissue-specific imprinting of G(S)alpha.

PMID- 10913165
TI  - Coordinate transcriptional and translational regulation of ferritin in response
      to oxidative stress.
AB  - The global increase in transcription of cytoprotective genes induced in response
      to oxidative challenge has been termed the antioxidant response. Ferritin serves
      as the major iron-binding protein in nonhematopoietic tissues, limiting the
      catalytic availability of iron for participation in oxygen radical generation.
      Here we demonstrate that ferritin is a participant in the antioxidant response
      through a genetically defined electrophile response element (EpRE). The EpRE of
      ferritin H identified in this report exhibits sequence similarity to EpRE motifs
      found in antioxidant response genes such as those encoding NAD(P)H:quinone
      reductase, glutathione S-transferase, and heme oxygenase. However, the EpRE of
      ferritin H is unusual in structure, comprising two bidirectional motifs arranged
      in opposing directions on complementary DNA strands. In addition to EpRE-mediated
      transcriptional activation, we demonstrate that ferritin is subject to time
      dependent translational control through regulation of iron-regulatory proteins
      (IRP). Although IRP-1 is initially activated to its RNA binding (ferritin
      repressing) state by oxidants, it rapidly returns to its basal state. This
      permits the translation of newly synthesized ferritin transcripts and ultimately
      leads to increased levels of ferritin protein synthesis following oxidant
      exposure. Taken together, these results clarify the complex transcriptional and
      translational regulatory mechanisms that contribute to ferritin regulation in
      response to prooxidant stress and establish a role for ferritin in the
      antioxidant response.

PMID- 10913167
TI  - Aldose reductase-deficient mice develop nephrogenic diabetes insipidus.
AB  - Aldose reductase (ALR2) is thought to be involved in the pathogenesis of various
      diseases associated with diabetes mellitus, such as cataract, retinopathy,
      neuropathy, and nephropathy. However, its physiological functions are not well
      understood. We developed mice deficient in this enzyme and found that they had no
      apparent developmental or reproductive abnormality except that they drank and
      urinated significantly more than their wild-type littermates. These ALR2
      deficient mice exhibited a partially defective urine-concentrating ability,
      having a phenotype resembling that of nephrogenic diabetes insipidus.

PMID- 10913166
TI  - TEL, a putative tumor suppressor, modulates cell growth and cell morphology of
      ras-transformed cells while repressing the transcription of stromelysin-1.
AB  - TEL is a member of the ETS family of transcription factors that interacts with
      the mSin3 and SMRT corepressors to regulate transcription. TEL is biallelically
      disrupted in acute leukemia, and loss of heterozygosity at the TEL locus has been
      observed in various cancers. Here we show that expression of TEL in Ras
      transformed NIH 3T3 cells inhibits cell growth in soft agar and in normal
      cultures. Unexpectedly, cells expressing both Ras and TEL grew as aggregates. To
      begin to explain the morphology of Ras-plus TEL-expressing cells, we demonstrated
      that the endogenous matrix metalloproteinase stromelysin-1 was repressed by TEL.
      TEL bound sequences in the stromelysin-1 promoter and repressed the promoter in
      transient-expression assays, suggesting that it is a direct target for TEL
      mediated regulation. Mutants of TEL that removed a binding site for the mSin3A
      corepressor but retained the ETS domain failed to repress stromelysin-1. When BB
      94, a matrix metalloproteinase inhibitor, was added to the culture medium of Ras
      expressing cells, it caused a cell aggregation phenotype similar to that caused
      by TEL expression. In addition, TEL inhibited the invasiveness of Ras-transformed
      cells in vitro and in vivo. Our results suggest that TEL acts as a tumor
      suppressor, in part, by transcriptional repression of stromelysin-1.

PMID- 10913168
TI  - Artificially recruited TATA-binding protein fails to remodel chromatin and does
      not activate three promoters that require chromatin remodeling.
AB  - Transcriptional activators are believed to work in part by recruiting general
      transcription factors, such as TATA-binding protein (TBP) and the RNA polymerase
      II holoenzyme. Activation domains also contribute to remodeling of chromatin in
      vivo. To determine whether these two activities represent distinct functions of
      activation domains, we have examined transcriptional activation and chromatin
      remodeling accompanying artificial recruitment of TBP in yeast (Saccharomyces
      cerevisiae). We measured transcription of reporter genes with defined chromatin
      structure by artificial recruitment of TBP and found that a reporter gene whose
      TATA element was relatively accessible could be activated by artificially
      recruited TBP, whereas two promoters, GAL10 and CHA1, that have accessible
      activator binding sites, but nucleosomal TATA elements, could not. A third
      reporter gene containing the HIS4 promoter could be activated by GAL4-TBP only
      when a RAP1 binding site was present, although RAP1 alone could not activate the
      reporter, suggesting that RAP1 was needed to open the chromatin structure to
      allow activation. Consistent with this interpretation, artificially recruited TBP
      was unable to perturb nucleosome positioning via a nucleosomal binding site, in
      contrast to a true activator such as GAL4, or to perturb the TATA-containing
      nucleosome at the CHA1 promoter. Finally, we show that activation of the GAL10
      promoter by GAL4, which requires chromatin remodeling, can occur even in swi gcn5
      yeast, implying that remodeling pathways independent of GCN5, the SWI-SNF
      complex, and TFIID can operate during transcriptional activation in vivo.

PMID- 10913169
TI  - Cks1 is required for G(1) cyclin-cyclin-dependent kinase activity in budding
      yeast.
AB  - p13(suc1) (Cks) proteins have been implicated in the regulation of cyclin
      dependent kinase (CDK) activity. However, the mechanism by which Cks influences
      the function of cyclin-CDK complexes has remained elusive. We show here that Cks1
      is required for the protein kinase activity of budding yeast G(1) cyclin-CDK
      complexes. Cln2 and Cdc28 subunits coexpressed in baculovirus-infected insect
      cells fail to exhibit protein kinase activity towards multiple substrates in the
      absence of Cks1. Cks1 can both stabilize Cln2-Cdc28 complexes and activate intact
      complexes in vitro, suggesting that it plays multiple roles in the biogenesis of
      active G(1) cyclin-CDK complexes. In contrast, Cdc28 forms stable, active
      complexes with the B-type cyclins Clb4 and Clb5 regardless of whether Cks1 is
      present. The levels of Cln2-Cdc28 and Cln3-Cdc28 protein kinase activity are
      severely reduced in cks1-38 cell extracts. Moreover, phosphorylation of G(1)
      cyclins, which depends on Cdc28 activity, is reduced in cks1-38 cells. The role
      of Cks1 in promoting G(1) cyclin-CDK protein kinase activity both in vitro and in
      vivo provides a simple molecular rationale for the essential role of CKS1 in
      progression through G(1) phase in budding yeast.

PMID- 10913171
TI  - Mitochondrial protein import motor: the ATPase domain of matrix Hsp70 is crucial
      for binding to Tim44, while the peptide binding domain and the carboxy-terminal
      segment play a stimulatory role.
AB  - The import motor for preproteins that are targeted into the mitochondrial matrix
      consists of the matrix heat shock protein Hsp70 (mtHsp70) and the translocase
      subunit Tim44 of the inner membrane. mtHsp70 interacts with Tim44 in an ATP
      dependent reaction cycle, binds to preproteins in transit, and drives their
      translocation into the matrix. While different functional mechanisms are
      discussed for the mtHsp70-Tim44 machinery, little is known about the actual mode
      of interaction of both proteins. Here, we have addressed which of the three Hsp70
      regions, the ATPase domain, the peptide binding domain, or the carboxy-terminal
      segment, are required for the interaction with Tim44. By two independent means, a
      two-hybrid system and coprecipitation of mtHsp70 constructs imported into
      mitochondria, we show that the ATPase domain interacts with Tim44, although with
      a reduced efficiency compared to the full-length mtHsp70. The interaction of the
      ATPase domain with Tim44 is ATP sensitive. The peptide binding domain and carboxy
      terminal segment are unable to bind to Tim44 in the absence of the ATPase domain,
      but both regions enhance the interaction with Tim44 in the presence of the ATPase
      domain. We conclude that the ATPase domain of mtHsp70 is essential for and
      directly interacts with Tim44, clearly separating the mtHsp70-Tim44 interaction
      from the mtHsp70-substrate interaction.

PMID- 10913170
TI  - Regulation of c-SRC activity and function by the adapter protein CAS.
AB  - SRC family kinases play essential roles in a variety of cellular functions,
      including proliferation, survival, differentiation, and apoptosis. The activities
      of these kinases are regulated by intramolecular interactions and by heterologous
      binding partners that modulate the transition between active and inactive
      structural conformations. p130(CAS) (CAS) binds directly to both the SH2 and SH3
      domains of c-SRC and therefore has the potential to structurally alter and
      activate this kinase. In this report, we demonstrate that overexpression of full
      length CAS in COS-1 cells induces c-SRC-dependent tyrosine phosphorylation of
      multiple endogenous cellular proteins. A carboxy-terminal fragment of CAS (CAS
      CT), which contains the c-SRC binding site, was sufficient to induce c-SRC
      dependent protein tyrosine kinase activity, as measured by tyrosine
      phosphorylation of cortactin, paxillin, and, to a lesser extent, focal adhesion
      kinase. A single amino acid substitution located in the binding site for the SRC
      SH3 domain of CAS-CT disrupted CAS-CT's interaction with c-SRC and inhibited its
      ability to induce tyrosine phosphorylation of cortactin and paxillin. Murine
      C3H10T1/2 fibroblasts that expressed elevated levels of tyrosine phosphorylated
      CAS and c-SRC-CAS complexes exhibited an enhanced ability to form colonies in
      soft agar and to proliferate in the absence of serum or growth factors. CAS-CT
      fully substituted for CAS in mediating growth in soft agar but was less effective
      in promoting serum-independent growth. These data suggest that CAS plays an
      important role in regulating specific signaling pathways governing cell growth
      and/or survival, in part through its ability to interact with and modulate the
      activity of c-SRC.

PMID- 10913172
TI  - Rfc5, in cooperation with rad24, controls DNA damage checkpoints throughout the
      cell cycle in Saccharomyces cerevisiae.
AB  - RAD24 and RFC5 are required for DNA damage checkpoint control in the budding
      yeast Saccharomyces cerevisiae. Rad24 is structurally related to replication
      factor C (RFC) subunits and associates with RFC subunits Rfc2, Rfc3, Rfc4, and
      Rfc5. rad24Delta mutants are defective in all the G(1)-, S-, and G(2)/M-phase DNA
      damage checkpoints, whereas the rfc5-1 mutant is impaired only in the S-phase DNA
      damage checkpoint. Both the RFC subunits and Rad24 contain a consensus sequence
      for nucleoside triphosphate (NTP) binding. To determine whether the NTP-binding
      motif is important for Rad24 function, we mutated the conserved lysine(115)
      residue in this motif. The rad24-K115E mutation, which changes lysine to
      glutamate, confers a complete loss-of-function phenotype, while the rad24-K115R
      mutation, which changes lysine to arginine, shows no apparent phenotype. Although
      neither rfc5-1 nor rad24-K115R single mutants are defective in the G(1)- and
      G(2)/M-phase DNA damage checkpoints, rfc5-1 rad24-K115R double mutants become
      defective in these checkpoints. Coimmunoprecipitation experiments revealed that
      Rad24(K115R) fails to interact with the RFC proteins in rfc5-1 mutants. Together,
      these results indicate that RFC5, like RAD24, functions in all the G(1)-, S- and
      G(2)/M-phase DNA damage checkpoints and suggest that the interaction of Rad24
      with the RFC proteins is essential for DNA damage checkpoint control.

PMID- 10913174
TI  - TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of
      the receptor.
AB  - The extracellular region of the nerve growth factor (NGF) receptor, TrkA,
      contains two immunoglobulin (Ig)-like domains that are required for specific
      ligand binding. We have investigated the possible role of these two Ig-like
      domains in receptor dimerization and activation by using different mutants of the
      TrkA extracellular region. Deletions of each Ig-like domain, of both, and of the
      entire extracellular region were made. To probe the structural constraints on
      ligand-independent receptor dimerization, chimeric receptors were generated by
      swapping the Ig-like domains of the TrkA receptor for the third or fourth Ig-like
      domain of c-Kit. We also introduced single-amino-acid changes in conserved
      residues within the Ig-like domains of TrkA. Most of these TrkA variants did not
      bind NGF, and their expression in PC12nnr5 cells, which lack endogenous TrkA,
      promoted ligand-independent neurite outgrowth. Some TrkA mutant receptors induced
      malignant transformation of Rat-1 cells, as assessed by measuring proliferation
      in the absence of serum, anchorage-independent growth, and tumorigenesis in nude
      mice. These mutants exhibited constitutive phosphorylation and spontaneous
      dimerization consistent with their biological activities. Our data suggest that
      spontaneous dimerization of TrkA occurs when the structure of the Ig-like domains
      is altered, implying that the intact domains inhibit receptor dimerization in the
      absence of NGF.

PMID- 10913173
TI  - Relief of two built-In autoinhibitory mechanisms in P-TEFb is required for
      assembly of a multicomponent transcription elongation complex at the human
      immunodeficiency virus type 1 promoter.
AB  - Tat stimulation of human immunodeficiency virus type 1 (HIV-1) transcription
      requires Tat-dependent recruitment of human positive transcription elongation
      factor b (P-TEFb) to the HIV-1 promoter and the formation on the trans-acting
      response element (TAR) RNA of a P-TEFb-Tat-TAR ternary complex. We show here that
      the P-TEFb heterodimer of Cdk9-cyclin T1 is intrinsically incapable of forming a
      stable complex with Tat and TAR due to two built-in autoinhibitory mechanisms in
      P-TEFb. Both mechanisms exert little effect on the P-TEFb-Tat interaction but
      prevent the P-TEFb-Tat complex from binding to TAR RNA. The first autoinhibition
      arises from the unphosphorylated state of Cdk9, which establishes a P-TEFb
      conformation unfavorable for TAR recognition. Autophosphorylation of Cdk9
      overcomes this inhibition by inducing conformational changes in P-TEFb, thereby
      exposing a region in cyclin T1 for possible TAR binding. An intramolecular
      interaction between the N- and C-terminal regions of cyclin T1 sterically blocks
      the P-TEFb-TAR interaction and constitutes the second autoinhibitory mechanism.
      This inhibition is relieved by the binding of the C-terminal region of cyclin T1
      to the transcription elongation factor Tat-SF1 and perhaps other cellular
      factors. Upon release from the intramolecular interaction, the C-terminal region
      also interacts with RNA polymerase II and is required for HIV-1 transcription,
      suggesting its role in bridging the P-TEFb-Tat-TAR complex and the basal
      elongation apparatus. These data reveal novel control mechanisms for the assembly
      of a multicomponent transcription elongation complex at the HIV-1 promoter.

PMID- 10913175
TI  - Receptor-like protein tyrosine phosphatase alpha homodimerizes on the cell
      surface.
AB  - We reported previously that the N-terminal D1 catalytic domain of receptor
      protein-tyrosine phosphatase alpha (RPTPalpha) forms a symmetrical, inhibited
      dimer in a crystal structure, in which a helix-turn-helix wedge element from one
      monomer is inserted into the catalytic cleft of the other monomer. Previous
      functional studies also suggested that dimerization inhibits the biological
      activity of a CD45 chimeric RPTP and the catalytic activity of an isolated
      RPTPsigma D1 catalytic domain. Most recently, we have also shown that enforced
      dimerization inhibits the biological activity of full-length RPTPalpha in a wedge
      dependent manner. The physiological significance of such inhibition is unknown,
      due to a lack of understanding of how RPTPalpha dimerization is regulated in
      vivo. In this study, we show that transiently expressed cell surface RPTPalpha
      exists predominantly as homodimers, suggesting that dimerization-mediated
      inhibition of RPTPalpha biological activity is likely to be physiologically
      relevant. Consistent with our published and unpublished crystallographic data, we
      show that mutations in the wedge region of D1 catalytic domain and deletion of
      the entire D2 catalytic domain independently reduced but did not abolish
      RPTPalpha homodimerization, suggesting that both domains are critically involved
      but that neither is essential for homodimerization. Finally, we also provide
      evidence that both the RPTPalpha extracellular domain and the transmembrane
      domain were independently able to homodimerize. These results lead us to propose
      a zipper model in which inactive RPTPalpha dimers are stabilized by multiple,
      relatively weak dimerization interfaces. Dimerization in this manner would
      provide a potential mechanism for negative regulation of RPTPalpha. Such
      RPTPalpha dimers could be activated by extracellular ligands or intracellular
      binding proteins that induce monomerization or by intracellular signaling events
      that induce an open conformation of the dimer.

PMID- 10913176
TI  - Repression of RNA polymerase I transcription by the tumor suppressor p53.
AB  - The tumor suppressor protein p53 is frequently inactivated in tumors. It
      functions as a transcriptional activator as well as a repressor for a number of
      viral and cellular promoters transcribed by RNA polymerase II (Pol II) and by RNA
      Pol III. Moreover, it appears that p53 also suppresses RNA Pol I transcription.
      In this study, we examined the molecular mechanism of Pol I transcriptional
      inhibition by p53. We show that wild-type, but not mutant, p53 can repress Pol I
      transcription from a human rRNA gene promoter in cotransfection assays.
      Furthermore, we show that recombinant p53 inhibits rRNA transcription in a cell
      free transcription system. In agreement with these results, p53-null epithelial
      cells display an increased Pol I transcriptional activity compared to that of
      epithelial cells that express p53. However, both cell lines display comparable
      Pol I factor protein levels. Our biochemical analysis shows that p53 prevents the
      interaction between SL1 and UBF. Protein-protein interaction assays indicate that
      p53 binds to SL1, and this interaction is mostly mediated by direct contacts with
      TATA-binding protein and TAF(I)110. Moreover, template commitment assays show
      that while the formation of a UBF-SL1 complex can partially relieve the
      inhibition of transcription, only the assembly of a UBF-SL1-Pol I initiation
      complex on the rDNA promoter confers substantial protection against p53
      inhibition. In summary, our results suggest that p53 represses RNA Pol I
      transcription by directly interfering with the assembly of a productive
      transcriptional machinery on the rRNA promoter.

PMID- 10913177
TI  - The two proteins Pat1p (Mrt1p) and Spb8p interact in vivo, are required for mRNA
      decay, and are functionally linked to Pab1p.
AB  - We report here the characterization of a bypass suppressor of pab1Delta which
      leads to a fourfold stabilization of the unstable MFA2 mRNA. Cloning of the wild
      type gene for that suppressor reveals that it is identical to PAT1 (YCR077c), a
      gene whose product was reported to interact with Top2p. PAT1 is not an essential
      gene, but its deletion leads to a thermosensitive phenotype. Further analysis has
      shown that PAT1 is allelic with mrt1-3, a mutation previously reported to affect
      decapping and to bypass suppress pab1Delta, as is also the case for dcp1, spb8,
      and mrt3. Coimmunoprecipitation experiments show that Pat1p is associated with
      Spb8p. On sucrose gradients, the two proteins cosediment with fractions
      containing the polysomes. In the absence of Pat1p, however, Spb8p no longer
      cofractionates with the polysomes, while the removal of Spb8p leads to a sharp
      decrease in the level of Pat1p. Our results suggest that some of the factors
      involved in mRNA degradation could be associated with the mRNA that is still
      being translated, awaiting a specific signal to commit the mRNA to the
      degradation pathway.

PMID- 10913178
TI  - A U-rich element in the 5' untranslated region is necessary for the translation
      of p27 mRNA.
AB  - Increased translation of p27 mRNA correlates with withdrawal of cells from the
      cell cycle. This raised the possibility that antimitogenic signals might mediate
      their effects on p27 expression by altering complexes that formed on p27 mRNA,
      regulating its translation. In this report, we identify a U-rich sequence in the
      5' untranslated region (5'UTR) of p27 mRNA that is necessary for efficient
      translation in proliferating and nonproliferating cells. We show that a number of
      factors bind to the 5'UTR in vitro in a manner dependent on the U-rich element,
      and their availability in the cytosol is controlled in a growth- and cell cycle
      dependent fashion. One of these factors is HuR, a protein previously implicated
      in mRNA stability, transport, and translation. Another is hnRNP C1 and C2,
      proteins implicated in mRNA processing and the translation of a specific subset
      of mRNAs expressed in differentiated cells. In lovastatin-treated MDA468 cells,
      the mobility of the associated hnRNP C1 and C2 proteins changed, and this
      correlated with increased p27 expression. Together, these data suggest that the U
      rich dependent RNP complex on the 5'UTR may regulate the translation of p27 mRNA
      and may be a target of antimitogenic signals.

PMID- 10913179
TI  - Genetic interactions between TFIIS and the Swi-Snf chromatin-remodeling complex.
AB  - The eukaryotic transcript elongation factor TFIIS enables RNA polymerase II to
      read through blocks to elongation in vitro and interacts genetically with a
      variety of components of the transcription machinery in vivo. In Saccharomyces
      cerevisiae, the gene encoding TFIIS (PPR2) is not essential, and disruption
      strains exhibit only mild phenotypes and an increased sensitivity to 6-azauracil.
      The nonessential nature of TFIIS encouraged the use of a synthetic lethal screen
      to elucidate the in vivo roles of TFIIS as well as provide more information on
      other factors involved in the regulation of transcript elongation. Several genes
      were identified that are necessary for either cell survival or robust growth when
      the gene encoding TFIIS has been disrupted. These include UBP3, KEX2, STT4, and
      SWI2/SNF2. SWI1 and SNF5 disruptions were also synthetically lethal with
      ppr2Delta, suggesting that the reduced ability to remodel chromatin confers the
      synthetic phenotype. The synthetic phenotypes show marked osmosensitivity and
      cytoskeletal defects, including a terminal hyperelongated bud phenotype with the
      Swi-Snf complex. These results suggest that genes important in osmoregulation,
      cell membrane synthesis and integrity, and cell division may require the Swi-Snf
      complex and TFIIS for efficient transcription. The detection of these genetic
      interactions provides another functional link between the Swi-Snf complex and the
      elongation machinery.

PMID- 10913180
TI  - Receptor isoforms mediate opposing proliferative effects through gbetagamma
      activated p38 or Akt pathways.
AB  - The opposing effects on proliferation mediated by G-protein-coupled receptor
      isoforms differing in their COOH termini could be correlated with the abilities
      of the receptors to differentially activate p38, implicated in apoptotic events,
      or phosphatidylinositol 3-kinase (PI 3-K), which provides a source of survival
      signals. These contrasting growth responses of the somatostatin sst(2) receptor
      isoforms, which couple to identical Galpha subunit pools (Galpha(i3) > Galpha(i2)
      >> Galpha(0)), were both inhibited following betagamma sequestration. The
      sst(2(a)) receptor-mediated ATF-2 activation and inhibition of proliferation
      induced by basic fibroblast growth factor (bFGF) were dependent on prolonged
      phosphorylation of p38. In contrast, cell proliferation and the associated
      transient phosphorylation of Akt and p70(rsk) induced by sst(2(b)) receptors were
      blocked by the PI 3-K inhibitor LY 294002. Stimulation with bFGF alone had no
      effect on the activity of either p38 or Akt but markedly enhanced p38
      phosphorylation mediated by sst(2(a)) receptors, suggesting that a complex
      interplay exists between the transduction cascades activated by these distinct
      receptor types. In addition, although all receptors mediated a sustained
      activation of extracellular signal-regulated kinases (ERK1 and ERK2), induction
      of the tumor suppressor p21(cip1) was detected only following amplification of
      ERK and p38 phosphorylation by concomitant bFGF and sst(2(a)) receptor
      activation. Expression of constitutively active Akt in the presence of a p38
      inhibitor enabled a proliferative response to be detected in sst(2(a)) receptor
      expressing cells. These findings demonstrate that the duration of activation and
      a critical balance between the mitogen-activated protein kinase and PI 3-K
      pathways are important for controlling cell proliferation and that the COOH
      termini of the sst(2) receptor isoforms may determine the selection of
      appropriate betagamma-pairings necessary for interaction with distinct kinase
      cascades.

PMID- 10913181
TI  - C/EBPalpha inhibits cell growth via direct repression of E2F-DP-mediated
      transcription.
AB  - Using an inducible transcription system which allows the regulated expression of
      C/EBP isoforms in tissue culture cells, we have found that the ectopic expression
      of C/EBPalpha, at a level comparable to that found in normal liver tissue, has a
      pronounced antimitogenic effect in mouse L cells and NIH 3T3 cells. The
      inhibition of cell division by C/EBPalpha in mouse cells cannot be reversed by
      simian virus 40 T antigen, by oncogenic ras, or by adenovirus E1a protein. When
      expressed in thymidine kinase-deficient L cells or 3T3 cells, C/EBPalpha is
      detected in a protein complex which binds to the E2F binding sites found in the
      promoters of the genes for E2F-1 and dihydrofolate reductase (DHFR). Bacterially
      expressed C/EBPalpha has no affinity for these E2F sites, but when recombinant
      C/EBPalpha is added to nuclear extracts from mouse fibroblasts, a new E2F binding
      activity appears, which contains the C/EBPalpha protein. Using an E2F-DP1
      responsive promoter linked to a reporter gene, it can be shown that C/EBPalpha
      directly inhibits the induction of this promoter by E2F-DP1 in transient
      transfection assays. Furthermore, C/EBPalpha can be shown to inhibit the S-phase
      induction of the E2F and DHFR promoters in permanent cell lines. These findings
      delineate a straightforward mechanism for C/EBPalpha-mediated cell growth arrest
      through repression of E2F-DP-mediated S-phase transcription.

PMID- 10913182
TI  - Separation of membrane trafficking and actin remodeling functions of ARF6 with an
      effector domain mutant.
AB  - The ADP-ribosylation factor 6 (ARF6) GTPase has a dual function in cells,
      regulating membrane traffic and organizing cortical actin. ARF6 activation is
      required for recycling of the endosomal membrane back to the plasma membrane (PM)
      and also for ruffling at the PM induced by Rac. Additionally, ARF6 at the PM
      induces the formation of actin-containing protrusions. To identify sequences in
      ARF6 that are necessary for these distinct functions, we examined the behavior of
      a chimeric protein of ARF1 and ARF6. The 1-6 chimera (with the amino half of ARF1
      and the carboxyl half of ARF6) localized like ARF6 in HeLa cells and moved
      between the endosome and PM, but it did not form protrusions, an ARF6 effector
      function. Two residues in the amino-terminal half of ARF6, Q37 and S38, when
      substituted into the 1-6 chimera allowed protrusion formation, whereas removal of
      these residues from ARF6 resulted in an inability to form protrusions.
      Interestingly, expression of 1-6 in cells selectively inhibited protrusions
      induced by wild-type ARF6 but had no effect on ARF6-regulated membrane movement
      or Rac-induced ruffling. Thus, we have uncoupled two functions of ARF6, one
      involved in membrane trafficking, which is necessary for Rac ruffling, and
      another involved in protrusion formation.

PMID- 10913183
TI  - Induction of cell cycle progression and acceleration of apoptosis are two
      separable functions of c-Myc: transrepression correlates with acceleration of
      apoptosis.
AB  - Analysis of amino-terminus mutants of c-Myc has allowed a systematic study of the
      interrelationship between Myc's ability to regulate transcription and its
      apoptotic, proliferative, and transforming functions. First, we have found that c
      Myc-accelerated apoptosis does not directly correlate with its ability to
      transactivate transcription using the endogenous ornithine decarboxylase (ODC)
      gene as readout for transactivation. Furthermore, deletion of the conserved c-Myc
      box I domain implicated in transactivation does not inhibit apoptosis. Second,
      the ability of c-Myc to repress transcription, using the gadd45 gene as a
      readout, correlates with its ability to accelerate apoptosis. A conserved region
      of c-Myc implicated in mediating transrepression is absolutely required for c-Myc
      accelerated apoptosis. Third, a lymphoma-derived Thr58Ala mutation diminishes c
      Myc-accelerated apoptosis through a decreased ability to induce the release of
      cytochrome c from mitochondria. This mutation in a potential phosphorylation site
      does not affect cell cycle progression, providing genetic evidence that induction
      of cell cycle progression and acceleration of apoptosis are two separable
      functions of c-Myc. Finally, we show that the increased ability of Thr58Ala
      mutant to elicit cellular transformation correlates with its diminished ability
      to accelerate apoptosis. Bcl-2 overexpression blocked and the lymphoma-associated
      Thr58Ala mutation decreased c-Myc-accelerated apoptosis, and both led to a
      significant increase in the ability of Rat1a cells to form colonies in soft agar.
      This enhanced transformation was greater in soft agar containing a low
      concentration of serum, suggesting that protection from apoptosis is a mechanism
      contributing to the increased ability of these cells to proliferate in
      suspension. Thus, we show here for the first time that, in addition to mutations
      in complementary antiapoptotic genes, c-Myc itself can acquire mutations that
      potentiate neoplastic transformation by affecting apoptosis independently of cell
      cycle progression.

PMID- 10913184
TI  - Physical association of eukaryotic initiation factor 4G (eIF4G) with eIF4A
      strongly enhances binding of eIF4G to the internal ribosomal entry site of
      encephalomyocarditis virus and is required for internal initiation of
      translation.
AB  - Mammalian eukaryotic initiation factor 4GI (eIF4GI) may be divided into three
      similarly sized regions. The central region (amino acids [aa] 613 to 1090) binds
      eIF3, eIF4A, and the encephalomyocarditis virus (EMCV) internal ribosomal entry
      site (IRES) and mediates initiation on this RNA. We identified the regions of
      eIF4GI that are responsible for its specific interaction with the IRES and that
      are required to mediate 48S complex formation on the IRES in vitro. Mutational
      analysis demarcated the IRES binding fragment of eIF4GI (aa 746 to 949) and
      indicated that it does not resemble an RNA recognition motif (RRM)-like domain.
      An additional amino-terminal sequence (aa 722 to 746) was required for binding
      eIF4A and for 48S complex formation. eIF4GI bound the EMCV IRES and beta-globin
      mRNA with similar affinities, but association with eIF4A increased its affinity
      for the EMCV IRES (but not beta-globin RNA) by 2 orders of magnitude. On the
      other hand, eIF4GI mutants with defects in binding eIF4A were defective in
      mediating 48S complex formation even if they bound the IRES normally. These data
      indicate that the eIF4G-eIF4A complex, rather than eIF4G alone, is required for
      specific high-affinity binding to the EMCV IRES and for internal ribosomal entry
      on this RNA.

PMID- 10913185
TI  - RNA-Dependent replication and transcription of hepatitis delta virus RNA involve
      distinct cellular RNA polymerases.
AB  - Cellular DNA-dependent RNA polymerase II (pol II) has been postulated to carry
      out RNA-dependent RNA replication and transcription of hepatitis delta virus
      (HDV) RNA, generating a full-length (1.7-kb) RNA genome and a subgenomic-length
      (0.8-kb) mRNA. However, the supporting evidence for this hypothesis was ambiguous
      because the previous experiments relied on DNA-templated transcription to
      initiate HDV RNA synthesis. Furthermore, there is no evidence that the same
      cellular enzyme is involved in the synthesis of both RNA species. In this study,
      we used a novel HDV RNA-based transfection approach, devoid of any artificial HDV
      cDNA intermediates, to determine the enzymatic and metabolic requirements for the
      synthesis of these two RNA species. We showed that HDV subgenomic mRNA
      transcription was inhibited by a low concentration of alpha-amanitin (<3
      microgram/ml) and could be partially restored by an alpha-amanitin-resistant
      mutant pol II; however, surprisingly, the synthesis of the full-length (1.7-kb)
      antigenomic RNA was not affected by alpha-amanitin to a concentration higher than
      25 microgram/ml. By several other criteria, such as the differing requirement for
      the de novo-synthesized hepatitis delta antigen and temperature dependence, we
      further showed that the metabolic requirements of subgenomic HDV mRNA synthesis
      are different from those for the synthesis of genomic-length HDV RNA and cellular
      pol II transcripts. The synthesis of the two HDV RNA species could also be
      uncoupled under several different conditions. These findings provide strong
      evidence that pol II, or proteins derived from pol II transcripts, is involved in
      mRNA transcription from the HDV RNA template. In contrast, the synthesis of the
      1.7-kb HDV antigenomic RNA appears not to be dependent on pol II. These results
      reveal that there are distinct molecular mechanisms for the synthesis of these
      two RNA species.

PMID- 10913186
TI  - A common motif within the negative regulatory regions of multiple factors
      inhibits their transcriptional synergy.
AB  - DNA regulatory elements frequently harbor multiple recognition sites for several
      transcriptional activators. The response mounted from such compound response
      elements is often more pronounced than the simple sum of effects observed at
      single binding sites. The determinants of such transcriptional synergy and its
      control, however, are poorly understood. Through a genetic approach, we have
      uncovered a novel protein motif that limits the transcriptional synergy of
      multiple DNA-binding regulators. Disruption of these conserved synergy control
      motifs (SC motifs) selectively increases activity at compound, but not single,
      response elements. Although isolated SC motifs do not regulate transcription when
      tethered to DNA, their transfer to an activator lacking them is sufficient to
      impose limits on synergy. Mechanistic analysis of the two SC motifs found in the
      glucocorticoid receptor N-terminal region reveals that they function irrespective
      of the arrangement of the receptor binding sites or their distance from the
      transcription start site. Proper function, however, requires the receptor's
      ligand-binding domain and an engaged dimer interface. Notably, the motifs are not
      functional in yeast and do not alter the effect of p160 coactivators, suggesting
      that they require other nonconserved components to operate. Many activators
      across multiple classes harbor seemingly unrelated negative regulatory regions.
      The presence of SC motifs within them, however, suggests a common function and
      identifies SC motifs as critical elements of a general mechanism to modulate
      higher-order interactions among transcriptional regulators.

PMID- 10913187
TI  - Transcriptional scaffold: CIITA interacts with NF-Y, RFX, and CREB to cause
      stereospecific regulation of the class II major histocompatibility complex
      promoter.
AB  - Scaffold molecules interact with multiple effectors to elicit specific signal
      transduction pathways. CIITA, a non-DNA-binding regulator of class II major
      histocompatibility complex (MHC) gene transcription, may serve as a
      transcriptional scaffold. Regulation of the class II MHC promoter by CIITA
      requires strict spatial-helical arrangements of the X and Y promoter elements.
      The X element binds RFX (RFX5/RFXANK-RFXB/RFXAP) and CREB, while Y binds NF-Y/CBF
      (NF-YA, NF-YB, and NF-YC). CIITA interacts with all three. In vivo analysis using
      both N-terminal and C-terminal deletion constructs identified critical domains of
      CIITA that are required for interaction with NF-YB, NF-YC, RFX5, RFXANK/RFXB, and
      CREB. We propose that binding of NF-Y/CBF, RFX, and CREB by CIITA results in a
      macromolecular complex which allows transcription factors to interact with the
      class II MHC promoter in a spatially and helically constrained fashion.

PMID- 10913188
TI  - Evidence for separable functions of Srp1p, the yeast homolog of importin alpha
      (Karyopherin alpha): role for Srp1p and Sts1p in protein degradation.
AB  - Srp1p (importin alpha) functions as the nuclear localization signal (NLS)
      receptor in Saccharomyces cerevisiae. The srp1-31 mutant is defective in this
      nuclear localization function, whereas an srp1-49 mutant exhibits defects that
      are unrelated to this localization function, as was confirmed by intragenic
      complementation between the two mutants. RPN11 and STS1 (DBF8) were identified as
      high-dosage suppressors of the srp1-49 mutation but not of the srp1-31 mutation.
      We found that Sts1p interacts directly with Srp1p in vitro and also in vivo, as
      judged by coimmunoprecipitation and two-hybrid analyses. Mutants of Sts1p that
      cannot interact with Srp1p are incapable of suppressing srp1-49 defects, strongly
      suggesting that Sts1p functions in a complex with Srp1p. STS1 also interacted
      with the second suppressor, RPN11, a subunit of the 26S proteasome, in the two
      hybrid system. Further, degradation of Ub-Pro-beta-galactosidase, a test
      substrate for the ubiquitin-proteasome system, was defective in srp1-49 but not
      in srp1-31. This defect in protein degradation was alleviated by overexpression
      of either RPN11 or STS1 in srp1-49. These results suggest a role for Srp1p in
      regulation of protein degradation separate from its well-established role as the
      NLS receptor.

PMID- 10913189
TI  - Rap2 as a slowly responding molecular switch in the Rap1 signaling cascade.
AB  - Rap2 is a member of the Ras family of GTPases and exhibits 60% identity to Rap1,
      but the function and regulation of Rap2 remain obscure. We found that, unlike the
      other Ras family proteins, the GTP-bound active form exceeded 50% of total Rap2
      protein in adherent cells. Guanine nucleotide exchange factors (GEFs) for Rap1,
      C3G, Epac (or cyclic AMP [cAMP]-GEF), CalDAG-GEFI, PDZ-GEF1, and GFR efficiently
      increased the level of GTP-Rap2 both in 293T cells and in vitro. GTPase
      activating proteins (GAPs) for Rap1, rap1GAPII and SPA-1, stimulated Rap2 GTPase,
      but with low efficiency. The half-life of GTP-Rap2 was significantly longer than
      that of GTP-Rap1 in 293T cells, indicating that low sensitivity to GAPs caused a
      high GTP/GDP ratio on Rap2. Rap2 bound to the Ras-binding domain of Raf and
      inhibited Ras-dependent activation of Elk1 transcription factor, as did Rap1. The
      level of GTP-Rap2 in rat 3Y1 fibroblasts was decreased by the expression of v
      Src, and expression of a GTPase-deficient Rap2 mutant inhibited v-Src-dependent
      transformation of 3Y1 cells. Altogether, Rap2 is regulated by a similar set of
      GEFs and GAPs as Rap1 and functions as a slowly responding molecular switch in
      the Rap1 signaling cascade.

PMID- 10913190
TI  - A lipopolysaccharide-specific enhancer complex involving Ets, Elk-1, Sp1, and
      CREB binding protein and p300 is recruited to the tumor necrosis factor alpha
      promoter in vivo.
AB  - The tumor necrosis factor alpha (TNF-alpha) gene is rapidly activated by
      lipopolysaccharide (LPS). Here, we show that extracellular signal-regulated
      kinase (ERK) kinase activity but not calcineurin phosphatase activity is required
      for LPS-stimulated TNF-alpha gene expression. In LPS-stimulated macrophages, the
      ERK substrates Ets and Elk-1 bind to the TNF-alpha promoter in vivo. Strikingly,
      Ets and Elk-1 bind to two TNF-alpha nuclear factor of activated T cells (NFAT)
      binding sites, which are required for calcineurin and NFAT-dependent TNF-alpha
      gene expression in lymphocytes. The transcription factors ATF-2, c-jun, Egr-1,
      and Sp1 are also inducibly recruited to the TNF-alpha promoter in vivo, and the
      binding sites for each of these activators are required for LPS-stimulated TNF
      alpha gene expression. Furthermore, assembly of the LPS-stimulated TNF-alpha
      enhancer complex is dependent upon the coactivator proteins CREB binding protein
      and p300. The finding that a distinct set of transcription factors associates
      with a fixed set of binding sites on the TNF-alpha promoter in response to LPS
      stimulation lends new insights into the mechanisms by which complex patterns of
      gene regulation are achieved.

PMID- 10913191
TI  - Analysis of the complex relationship between nuclear export and aryl hydrocarbon
      receptor-mediated gene regulation.
AB  - The aryl hydrocarbon receptor (AHR) contains signals for both nuclear import and
      nuclear export (NES). The purpose of the studies in this report was to determine
      the relationship between the nuclear export of the AHR and AHR-mediated gene
      regulation. Blockage of nuclear export in HepG2 cells with leptomycin B (LMB)
      resulted in increased levels of AHR-AHR nuclear translocator (ARNT) complex in
      the nucleus and correlative reductions in agonist-stimulated AHR degradation.
      However, LMB exposure inhibited agonist-mediated induction of numerous AHR
      responsive reporter genes by 75 to 89% and also inhibited induction of endogenous
      CYP1A1. LMB did not transform the AHR to a ligand binding species or affect
      activation by TCDD (2, 3,7,8-tetrachlorodibenzo-p-dioxin). Mutagenesis of
      leucines 66 and 71 of the putative AHR NES resulted in a protein with reduced
      function in dimerization to ARNT and binding to DNA, while alanine substitution
      at leucine 69 (AHR(A69)) resulted in an AHR that bound with ARNT and associated
      with DNA. AHR(A69) protein injected directly into the nuclei of E36 cells
      remained nuclear following 6 h of agonist stimulation. In transient-transfection
      assays, AHR(A69) accumulated within the nucleus was not degraded efficiently
      following agonist exposure. Finally, AHR(A69) supported induction of AHR
      responsive reporter genes in an agonist-dependent manner. These findings show
      that it is possible to generate an AHR protein defective in nuclear export that
      is functional in agonist-mediated gene induction. This implies that the negative
      effect of LMB on agonist-mediated gene induction is independent of the nuclear
      export of the AHR.

PMID- 10913192
TI  - RhoB alteration is necessary for apoptotic and antineoplastic responses to
      farnesyltransferase inhibitors.
AB  - Farnesyltransferase inhibitors (FTIs) are in clinical trials, but how they
      selectively inhibit malignant cell growth remains uncertain. One important player
      in this process appears to be RhoB, an endosomal Rho protein that regulates
      receptor trafficking. FTI treatment elicits a gain of the geranylgeranylated RhoB
      isoform (RhoB-GG) that occurs due to modification of RhoB by
      geranylgeranyltransferase I in drug-treated cells. Notably, this event is
      sufficient to mediate antineoplastic effects in murine models and human carcinoma
      cells. To further assess this gain-of-function mechanism and determine whether
      RhoB-GG has a necessary role in drug action, we examined the FTI response of
      murine fibroblasts that cannot express RhoB-GG due to homozygous deletion of the
      rhoB gene. Nullizygous (-/-) cells were susceptible to cotransformation by
      adenovirus E1A plus activated H-Ras but defective in their FTI response, despite
      complete inhibition of H-Ras prenylation. Actin cytoskeletal and phenotypic
      events were disrupted in -/- cells, implicating RhoB-GG in these effects.
      Interestingly, -/- cells were resistant to FTI-induced growth inhibition under
      anchorage-dependent but not anchorage-independent conditions, indicating that,
      while RhoB-GG is sufficient, it is not necessary for growth inhibition under all
      conditions. In contrast, -/- cells were resistant to FTI-induced apoptosis in
      vitro and in vivo. Significantly, the apoptotic defect of -/- cells compromised
      the antitumor efficacy of FTI in xenograft assays. This study offers genetic
      proof of the hypothesis that RhoB-GG is a crucial mediator of the antineoplastic
      effects of FTIs.

PMID- 10913193
TI  - Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its RNA
      binding ability.
AB  - Sik (mouse Src-related intestinal kinase) and its orthologue BRK (human breast
      tumor kinase) are intracellular tyrosine kinases that are distantly related to
      the Src family and have a similar structure, but they lack the myristoylation
      signal. Here we demonstrate that Sik and BRK associate with the RNA binding
      protein Sam68 (Src associated during mitosis, 68 kDa). We found that Sik
      interacts with Sam68 through its SH3 and SH2 domains and that the proline-rich P3
      region of Sam68 is required for Sik and BRK SH3 binding. In the transformed HT29
      adenocarcinoma cell cell line, endogenous BRK and Sam68 colocalize in Sam68-SLM
      nuclear bodies (SNBs), while transfected Sik and Sam68 are localized diffusely in
      the nucleoplasm of nontransformed NMuMG mammary epithelial cells. Transfected Sik
      phosphorylates Sam68 in SNBs in HT29 cells and in the nucleoplasm of NMuMG cells.
      In functional studies, expression of Sik abolished the ability of Sam68 to bind
      RNA and act as a cellular Rev homologue. While Sam68 is a substrate for Src
      family kinases during mitosis, Sik/BRK is the first identified tyrosine kinase
      that can phosphorylate Sam68 and regulate its activity within the nucleus, where
      it resides during most of the cell cycle.

PMID- 10913194
TI  - Activin betaC and betaE genes are not essential for mouse liver growth,
      differentiation, and regeneration.
AB  - The liver is an essential organ that produces several serum proteins, stores
      vital nutrients, and detoxifies many carcinogenic and xenobiotic compounds.
      Various growth factors positively regulate liver growth, but only a few negative
      regulators are known. Among the latter are the transforming growth factor beta
      (TGF-beta) superfamily members TGF-beta1 and activin A. To study the function of
      novel activin family members, we have cloned and generated mice deficient in the
      activin betaC and betaE genes. Expression analyses demonstrated that these novel
      genes are liver specific in adult mice. Here, we show by RNase protection that
      activin betaC transcripts are present in the liver beginning at embryonic day
      11.5 (E11.5) whereas activin betaE expression is detected starting from E17.5.
      Gene targeting in embryonic stem cells was used to generate mice with null
      mutations in either the individual activin betaC and betaE genes or both genes.
      In contrast to the structurally related activin betaA and betaB subunits, which
      are necessary for embryonic development and pituitary follicle-stimulating
      hormone homeostasis, mice deficient in activin betaC and betaE were viable,
      survived to adulthood, and demonstrated no reproductive abnormalities. Although
      activin betaC and betaE mRNAs are abundantly expressed in the liver of wild-type
      mice, the single and double mutants did not show any defects in liver development
      and function. Furthermore, in the homozygous mutant mice, liver regeneration
      after >70% partial hepatectomy was comparable to that in wild-type mice. Our
      results suggest that activin betaC and betaE are not essential for either
      embryonic development or liver function.

PMID- 10913196
TI  - Functional collaboration between different cyclin-dependent kinase inhibitors
      suppresses tumor growth with distinct tissue specificity.
AB  - The presence of two families of seven distinct mammalian cyclin-dependent kinase
      (CDK) inhibitor genes is thought to mediate the complexity of connecting a
      variety of cellular processes to the cell cycle control pathway. The distinct
      pattern of tissue expression of CDK inhibitor genes suggests that they may
      function as tumor suppressors with different tissue specificities. To test this
      hypothesis, we have characterized two strains of double mutant mice lacking
      either p18(INK4c) and p27(KIP1) or p18(INK4c) and p21(CIP1/WAF1). Loss of both
      p18 and p27 function resulted in the spontaneous development by 3 months of age
      of at least eight different types of hyperplastic tissues and/or tumors in the
      pituitary, adrenals, thyroid, parathyroid, testes, pancreas, duodenum, and
      stomach. Six of these hyperplastic tissues and tumors were in endocrine organs,
      and several types of tumors routinely developed within the same animal, a
      phenotype reminiscent of that seen in combined human multiple endocrine neoplasia
      syndromes. The p18-p21 double null mice, on the other hand, developed pituitary
      adenomas, multifocal gastric neuroendocrine hyperplasia, and lung
      bronchioalveolar tumors later in life. G(1) CDK2 and CDK4 kinase activities were
      increased in both normal and neoplastic tissues derived from mice lacking
      individual CDK inhibitors and were synergistically stimulated by the simultaneous
      loss of two CDK inhibitors. This indicates that an increase in G(1) CDK kinase
      activity is a critical step during but is not sufficient for tumor growth. Our
      results suggest that functional collaborations between distinct CDK inhibitor
      genes are tissue specific and confer yet another level of regulation in cell
      growth control and tumor suppression.

PMID- 10913195
TI  - Sp110 localizes to the PML-Sp100 nuclear body and may function as a nuclear
      hormone receptor transcriptional coactivator.
AB  - The nuclear body is a multiprotein complex that may have a role in the regulation
      of gene transcription. This structure is disrupted in a variety of human
      disorders including acute promyelocytic leukemia and viral infections, suggesting
      that alterations in the nuclear body may have an important role in the
      pathogenesis of these diseases. In this study, we identified a cDNA encoding a
      leukocyte-specific nuclear body component designated Sp110. The N-terminal
      portion of Sp110 was homologous to two previously characterized components of the
      nuclear body (Sp100 and Sp140). The C-terminal region of Sp110 was homologous to
      the transcription intermediary factor 1 (TIF1) family of proteins. High levels of
      Sp110 mRNA were detected in human peripheral blood leukocytes and spleen but not
      in other tissues. The levels of Sp110 mRNA and protein in the human promyelocytic
      leukemia cell line NB4 increased following treatment with all-trans retinoic acid
      (ATRA), and Sp110 localized to PML-Sp100 nuclear bodies in ATRA-treated NB4
      cells. Because of the structural similarities between Sp110 and TIF1 proteins,
      the effect of Sp110 on gene transcription was examined. An Sp110 DNA-binding
      domain fusion protein activated transcription of a reporter gene in transfected
      mammalian cells. In addition, Sp110 produced a marked increase in ATRA-mediated
      expression of a reporter gene containing a retinoic acid response element. Taken
      together, the results of this study demonstrate that Sp110 is a member of the
      Sp100/Sp140 family of nuclear body components and that Sp110 may function as a
      nuclear hormone receptor transcriptional coactivator. The predominant expression
      of Sp110 in leukocytes and the enhanced expression of Sp110 in NB4 cells treated
      with ATRA raise the possibility that Sp110 has a role in inducing differentiation
      of myeloid cells.

PMID- 10913199
TI  - Education

PMID- 10913197
TI  - BCR-ABL prevents c-jun-mediated and proteasome-dependent FUS (TLS) proteolysis
      through a protein kinase CbetaII-dependent pathway.
AB  - The DNA binding activity of FUS (also known as TLS), a nuclear pro-oncogene
      involved in multiple translocations, is regulated by BCR-ABL in a protein kinase
      CbetaII (PKCbetaII)-dependent manner. We show here that in normal myeloid
      progenitor cells FUS, although not visibly ubiquitinated, undergoes proteasome
      dependent degradation, whereas in BCR-ABL-expressing cells, degradation is
      suppressed by PKCbetaII phosphorylation. Replacement of serine 256 with the
      phosphomimetic aspartic acid prevents proteasome-dependent proteolysis of FUS,
      while the serine-256-to-alanine FUS mutant is unstable and susceptible to
      degradation. Ectopic expression of the phosphomimetic S256D FUS mutant in
      granulocyte colony-stimulating factor-treated 32Dcl3 cells induces massive
      apoptosis and inhibits the differentiation of the cells escaping cell death,
      while the degradation-prone S256A mutant has no effect on either survival or
      differentiation. FUS proteolysis is induced by c-Jun, is suppressed by BCR-ABL or
      Jun kinase 1, and does not depend on c-Jun transactivation potential,
      ubiquitination, or its interaction with Jun kinase 1. In addition, c-Jun-induced
      FUS proteasome-dependent degradation is enhanced by heterogeneous nuclear
      ribonucleoprotein (hnRNP) A1 and depends on the formation of a FUS-Jun-hnRNP A1
      containing complex and on lack of PKCbetaII phosphorylation at serine 256 but not
      on FUS ubiquitination. Thus, novel mechanisms appear to be involved in the
      degradation of FUS in normal myeloid cells; moreover, the ability of the BCR-ABL
      oncoprotein to suppress FUS degradation by the induction of posttranslational
      modifications might contribute to the phenotype of BCR-ABL-expressing
      hematopoietic cells.

PMID- 10913200
TI  - Presidential address: How shall we teach? How shall we learn? Educating hand
      surgeons in the new millennium.

PMID- 10913198
TI  - HES-1 repression of differentiation and proliferation in PC12 cells: role for the
      helix 3-helix 4 domain in transcription repression.
AB  - HES-1 is a Hairy-related basic helix-loop-helix protein with three evolutionarily
      conserved regions known to define its function as a transcription repressor. The
      basic region, helix-loop-helix domain, and WRPW motif have been characterized for
      their molecular function in DNA binding, dimer formation, and corepressor
      recruitment, respectively. In contrast, the function conferred by a fourth
      conserved region, the helix 3-helix 4 (H-3/4) domain, is not known. To better
      understand H-3/4 domain function, we expressed HES-1 variants under tetracycline
      inducible control in PC12 cells. As expected, the induced expression of moderate
      levels of wild-type HES-1 in PC12 cells strongly inhibited nerve growth factor
      induced differentiation. This repression was dependent on the H-3/4 domain.
      Unexpectedly, expression of HES-1 also arrested cell growth, an effect that could
      be reversed upon down regulation of HES-1. Concomitant with growth arrest, there
      was a strong reduction in bromodeoxyuridine incorporation and PCNA protein
      levels, although not in cyclin D1 expression. Expression of a HES-1 protein
      carrying the H-3/4 domain, but not the WRPW domain, still partially inhibited
      both proliferation and differentiation. Transcription assays in PC12 cells
      directly demonstrated that the H-3/4 domain can mediate DNA-binding-dependent
      transcription repression, even in the absence of corepressor recruitment by the
      WRPW motif. HES-1 expression strongly repressed transcription of the p21(cip1)
      promoter, a cyclin-cyclin-dependent kinase inhibitor up regulated during NGF
      induced differentiation, and the H-3/4 domain is necessary for this repression.
      Thus, the H-3/4 domain of HES-1 contributes to transcription repression
      independently of WRPW function, inhibits neurite formation, and facilitates two
      distinct and previously uncharacterized roles for HES-1: the inhibition of cell
      proliferation and the direct transcriptional repression of the NGF-induced gene,
      p21.

PMID- 10913201
TI  - Development of hand surgery: education of hand surgeons.
AB  - An organized experience in the care of hand injuries and infections was not
      available until World War II, when military hand centers were established. Dr
      Sterling Bunnell was designated as a special civilian consultant to the Secretary
      of War. The surgeons in the military services during World War II became the
      nucleus of the American Society for Surgery of the Hand (ASSH). Following World
      War II and the Korean War there was a major shift toward medical
      subspecialization, and the growth of surgery of the hand as a subspecialty
      parallels that trend. The ASSH initiated a coordinated effort to improve the
      educational experience, and in 1967 the ASSH Resident Training Committee was
      evaluating hand training programs. The ASSH developed a comprehensive program in
      continuing medical education, and received full accreditation from the American
      Medical Association Council on Medical Education. The American Medical
      Association has included hand surgery on its list of designated specialties since
      1975. In 1973, the bylaws of the American Board of Medical Specialties were
      revised to provide special certification. The ASSH developed a proposal for a
      certificate of added qualification in surgery of the hand that was presented to
      the three primary boards (orthopaedic, plastic, surgery) and the ad hoc joint
      Committee on Surgery of the Hand was organized in 1982. An application for a
      certificate of added qualification in surgery was developed by the Joint
      Committee on Surgery of the Hand and approved by all three boards in 1985 and the
      ABMS in 1986. The first examination for the certificate of added qualification in
      surgery was held in 1989.

PMID- 10913202
TI  - Enzyme injection as nonsurgical treatment of Dupuytren's disease.
AB  - Surgical fasciectomy is the currently accepted treatment of Dupuytren's disease.
      The goal of this study was to test the clinical safety and efficacy of
      clostridial collagenase injection as a nonsurgical treatment of Dupuytren's
      disease in a phase II open-label trial. Thirty-five Dupuytren's disease patients
      entered the study (32 men and 3 women). The mean age was 65 years. The first 6
      patients were treated following a dose escalation protocol and received 300, 600,
      1,200, 2,400, 4,800, and 9,600 U collagenase injected into the cord that was
      causing contracture of the metacarpophalangeal (MCP) joint. There were no
      beneficial clinical effects of these injections. The remaining 29 patients had
      collagenase injections at a dose level of 10,000 U, causing contractures of 34
      MCP joints, 9 proximal interphalangeal (PIP) joints, and 1 thumb. Twenty-eight of
      the 34 MCP joint contractures corrected to normal extension (0 degrees ) and 2 of
      the 34 MCP joint contractures corrected to 5 degrees of normal extension, with
      full range of motion, within 1 to 14 days of injection. In the patients with PIP
      joint contractures, 4 of the 9 joints corrected to normal (0 degrees ). One PIP
      joint corrected to within 10 degrees of normal and 2 corrected to within 15
      degrees of normal. There were 2 failures; these patients will require surgery.
      The mean follow-up period was 20.0 +/- 5.6 months for the MCP joints and 14.1 +/-
      6.6 months for the PIP joints. Clostridial collagenase injection of Dupuytren's
      cords causing MCP and PIP joint contractures appears to have merit as nonsurgical
      treatment of this disorder. Pending further placebo, double-blind studies,
      collagenase injection to treat Dupuytren's disease may be a safe and effective
      alternative to surgical fasciectomy.

PMID- 10913203
TI  - Sensory function of the neurovascular island flap in thumb reconstruction:
      comparison of original and modified procedures.
AB  - A study was conducted to examine the sensory function of thumbs that were
      reconstructed using 2 procedures: the original Littler neurovascular island flap
      (NVIF) procedure and a modification of the NVIF procedure in which the divided
      nerve of the transferred island flap is sutured to the original nerve of the
      thumb. Twenty-one patients with a mean follow-up period of 4.6 years were
      examined. Nine patients were treated with the NVIF procedure and 12 with the
      modified NVIF procedure. Paresthesia was observed more frequently in the patients
      treated with the original NVIF procedure. The Semmes-Weinstein test and the
      static and moving 2-point discrimination examinations showed no significant
      difference between the 2 groups. The pulp writing test showed significantly
      better results for the patients treated with the modified NVIF procedure. The
      transferred pedicle flap was fully recognized as representing the thumb in the
      modified procedure. In the original procedure, however, the sensibility of the
      transferred pedicle flap was recognized as coming from the thumb in only 61% of
      the cases; furthermore, the original procedure carried an additional disadvantage
      in that sensibility of the transferred pedicle flap was recognized as coming from
      both the donor and recipient sites.

PMID- 10913205
TI  - An outcome study of thumb reconstruction using microvascular toe transfer.
AB  - The purpose of this study was to evaluate outcomes following microvascular toe to
      thumb transfer in a cohort study using the Michigan Hand Outcomes Questionnaire,
      the 36-item Short-Form Health Survey, the Lower Limb Function Questionnaire, and
      standardized hand function tests. Twenty-one patients who had unilateral,
      isolated thumb amputations at the metacarpophalangeal joints were studied: 16
      patients had toe transfer and 5 patients did not have reconstruction. The mean
      follow-up period was 7.2 years (range, 3-13 years). Toe transfer patients showed
      statistically significantly better overall hand function (effect size = 1.4), ADL
      (effect size = 3.4), work performance (effect size = 2.1), aesthetics (effect
      size = 1.9), and satisfaction (effect size = 1.1). Functional testing showed that
      strength and dexterity of the toe transfer hands were comparable to the opposite
      normal hands. Foot donor site morbidity was minimal. No significant difference
      was found in the mean Lower Limb Function Questionnaire scores between the toe
      transfer patients (1.4) and the amputation patients who did not undergo
      reconstruction (1.6). The results of our study showed that patients with toe
      transfer have better hand function than patients with thumb amputations at the
      level of the metacarpophalangeal joints.

PMID- 10913204
TI  - Thumb reconstruction with a wraparound free flap according to the level of
      amputation.
AB  - We surgically treated 37 thumbs amputated distal or proximal to the
      metacarpophalangeal (MCP) joint using a wraparound free flap from the great toe
      for the reconstruction. We studied the functional results of the procedure
      according to the level of amputation and the fixation angle of the iliac bone
      block. The cases were divided into 2 groups: group 1, which comprised 25 cases
      with the level of amputation distal to the MCP joint, and group 2, which
      comprised 12 cases with the level of amputation at or proximal to the MCP joint.
      Opposition of the reconstructed thumb to the other fingers was completely
      possible in all cases in group 1. In group 2 opposition was completely possible
      in 6 cases in which the iliac bone block was fixated into the position of 30
      degrees flexion and 45 degrees internal rotation; in the remaining 6 cases, in
      which the graft was fixated into the position of 30 degrees flexion and 30
      degrees internal rotation, complete opposition of the reconstructed thumb to the
      ring and little fingers was not possible. We found that amputation of the thumb
      proximal to the MCP joint is not an absolute contraindication for the wraparound
      free flap reconstruction. We recommend fixating the iliac bone block into 30
      degrees flexion and 45 degrees internal rotation to obtain better functional
      outcome in cases with amputation at or proximal to the MCP joint.

PMID- 10913206
TI  - Topical and systemic anticoagulation in the treatment of absent or compromised
      venous outflow in replanted fingertips.
AB  - Adequate venous repair is not always possible in fingertip replantation. We have
      used topical and systemic anticoagulation for fingertip replantation to overcome
      venous congestion in cases without venous repair or in cases in which there is
      obstruction of a repaired vein. Our technique consists of continuous external
      bleeding via a stab incision on the paraungal area and dripping heparinized
      saline solution at the incision site to maintain external bleeding. From July
      1985 to December 1993, 157 fingers in 140 patients with complete amputation of
      the fingertip were replanted at Korea University Guro Hospital. Of these, 74
      fingers in 68 patients were managed by topical and systemic anticoagulation due
      to the impossibility of repair or obstruction of a repaired vein. The overall
      survival rate of the fingertip replantations was 76%; that of the topical and
      systemic anticoagulation group was 64%.

PMID- 10913207
TI  - Experience with the pedicled latissimus dorsi flap for finger reconstruction.
AB  - The pedicled latissimus dorsi flap was used for the reconstruction of finger
      function in 12 patients with severely disabled hands. The fascial origin of the
      muscle was sutured directly to finger flexors in 6 patients, and to extensors in
      the other 6 patients in the forearm without severing the neurovascular pedicle.
      Voluntary contraction of the muscle was obtained in all patients. Useful tendon
      gliding was achieved in 6 patients, thereby providing total active motion of
      fingers of >100 degrees. In the remaining 6 patients, however, several problems
      such as stiff finger joints prevented appropriate tendon gliding, resulting in
      total active motion of <60 degrees. When these problems are overcome, the
      pedicled latissimus dorsi muscle can yield satisfactory excursion for extrinsic
      tendons of the fingers. In contrast to free muscle transplantation, early and
      predictable recovery of function can be obtained using this particular technique
      without any risk of denervation of the muscle.

PMID- 10913208
TI  - Mechanisms of load transfer in the cadaver forearm: role of the interosseous
      membrane.
AB  - Forces transmitted through the distal ulna and proximal radius, relative motion
      between the radial head and capitellum, and measurements of tissue strain and
      local fiber tension within the central band of the interosseous membrane were
      recorded as cadaveric forearms were loaded axially through the wrist. With the
      elbow in valgus alignment (the radial head in direct contact with the
      capitellum), an average of 93% of force applied to the wrist was transferred
      directly through the radius to the elbow with no appreciable load transfer
      through the interosseous membrane. With varus alignment (initial gap between the
      radial head and capitellum) load applied to the wrist displaced the radius
      proximally an average of 1.1 mm until radial head contact occurred at a mean
      applied wrist force of 89.0 N. Proximal displacement of the radius generated
      strain in the central band of the interosseous membrane and created a more ulnar
      positive wrist, which in turn increased distal ulnar loading; distal ulnar force
      averaged 19% and interosseous membrane averaged 54% of applied wrist force.
      Distal ulnar loading was unaffected by 25 degrees wrist flexion-extension or by
      20 degrees of radioulnar deviation. With 40 degrees ulnar deviation, mean distal
      ulnar forces were 18% and 48% of applied wrist force for valgus and varus elbow
      alignments, respectively. Mean load-sharing percentages at the wrist and elbow
      were not significantly different between 222. 5 N and 133.5 N of applied force
      for any wrist position and were unaffected by the angle of elbow flexion.

PMID- 10913209
TI  - Role of the forearm interosseous ligament: is it more than just longitudinal load
      transfer?
AB  - The objective of our study was to measure 3-dimensional force vectors (magnitude
      and direction) acting in the forearm when load is applied to the hand and to
      measure the actual force in the interosseous ligament (IOL). Fourteen cadaveric
      forearms were loaded to 136 N of compression while special load cells measured
      force vectors in the forearm. Computer forearm models were used to display the 3
      dimensional force vector directions. The study results showed that the radius
      bears most of the load at the wrist but load on the radius at the elbow is
      reduced because the IOL transfers load to the ulna between the wrist and the
      elbow. In addition to this role in longitudinal load transfer, our measurement of
      3-dimensional forces allowed identification of transverse vectors which suggest
      that the IOL also functions to keep the radius and ulna from splaying apart. Our
      results imply that the IOL participates not only in longitudinal load transfer
      but also in the maintenance of transverse stability of the forearm during
      compressive load transfer from the hand to the elbow.

PMID- 10913210
TI  - The dorsopalmar stability of the distal radioulnar joint.
AB  - Sixteen fresh-frozen adult human cadaveric upper extremities were used in a
      biomechanical analysis of distal radioulnar joint (DRUJ) stability. The relative
      contribution to stability of the DRUJ by the surrounding anatomic structures
      presumed to stabilize the joint was analyzed with respect to forearm rotation and
      wrist flexion and extension using a purpose-built 4-axis materials testing
      machine. The dominant structures stabilizing the DRUJ were the ligamentous
      components of the triangular fibrocartilage complex proper. The major constraint
      to dorsal translation of the distal ulna relative to the radius is the palmar
      radioulnar ligament. Palmar translation of the distal ulna relative to the radius
      is constrained primarily by the dorsal radioulnar ligament, with secondary
      constraint provided by the palmar radioulnar ligament and interosseous membrane.
      The ulnocarpal ligaments and extensor carpi ulnaris subsheath did not contribute
      significantly to DRUJ stability; however, approximately 20% of DRUJ constraint is
      provided by the articular contact of the radius and ulna. These relationships
      were consistent regardless of wrist position or degree of forearm rotation.

PMID- 10913211
TI  - Dorsolateral biplane closing radial osteotomy in zero variant cases of Kienbock's
      disease.
AB  - Twenty-six patients with Lichtman stages II and III Kienbock's disease had
      biplane dorsolateral radial closing osteotomy to reduce the radial inclination
      and dorsal angles on the sagittal plane. The effects of the procedure were
      studied clinically, radiologically, and by magnetic resonance imaging in a 2- to
      6-year follow-up study (average follow-up period, 3.5 years). The signal
      intensity on T1- and T2-weighted images of the lunate increased after surgery in
      all patients, suggesting revascularization. The comparative advantages of this
      technique are discussed with regard to others currently used.

PMID- 10913212
TI  - Scaphoid stress fracture in a 13-year-old gymnast: a case report.
AB  - We present a 13-year-old gymnast with a stress fracture of the scaphoid.
      Treatment was successful with immobilization for 8 weeks in a long arm spica cast
      followed by 4 weeks in a short arm splint.

PMID- 10913213
TI  - The role of multiple strands and locking sutures on gap formation of flexor
      tendon repairs during cyclical loading.
AB  - The purpose of this study was to delineate the contribution of increasing suture
      strands and locking repair design in the prevention of gap formation using a
      cadaveric model for linear cyclical loading. Forty flexor digitorum profundus
      tendons were lacerated and repaired using locked and nonlocked variations of a 4-
      and 8-strand flexor tendon repair. An incremental cyclical loading protocol from
      25 N to 65 N was used. Comparison of the amount of Newton-cycles to reach 1, 2,
      3, and 4 mm of gap and the Newton-cycles withstood before failure was performed
      using 2-way ANOVA. The 8-strand repairs demonstrated significantly increased
      fatigue strength compared with the 4-strand repairs, but the number of strands
      crossing the repair site did not significantly affect gap resistance. The locked
      repairs demonstrated a significant increase in gap resistance to 1 and 2 mm
      compared with the nonlocked repairs, but the difference was not sustained at
      higher load cycles. There was no association between gap resistance and fatigue
      strength. We conclude that an increase in the number of strands significantly
      increases the fatigue strength of a tendon repair but does not alter its gap
      resistance to cyclic loading. Locking of the repair does provide additional gap
      resistance at the relatively low cyclical loads anticipated during the early
      healing period using an active motion rehabilitation protocol.

PMID- 10913215
TI  - Twenty-five-year follow-up evaluation of an active silicone/Dacron tendon
      interposition prosthesis: A case report.
AB  - A 19-year-old man sustained a severe avulsion wound of the dominant distal
      forearm, dividing the radial and ulnar arteries, median and ulnar nerves, and all
      flexor tendons. Initial treatment consisted of revascularization. Shortly
      thereafter he had sural nerve grafting of the median and ulnar nerves. This was
      followed by insertion of a silicone/Dacron tendon interposition prosthesis to
      reconstruct a 4-cm deficit in the flexor profundus tendons and the flexor
      pollicis longus tendon. Six weeks thereafter an opposition transfer using the
      extensor indicis proprius and a Brand type 2 intrinsic transfer using the
      extensor carpi radialis longus and a plantaris tendon graft were performed.
      Several months later an attempt was made to remove the prosthesis. It was encased
      in scar tissue, however, and left in place. Evaluation 25 years later revealed
      that the flexor tendons and prosthesis were functioning well.

PMID- 10913214
TI  - Flexor tendon grafting to the hand: an assessment of the intrasynovial donor
      tendon-A preliminary single-cohort study.
AB  - We report the results of a pilot study using intrasynovial donor tendons for
      flexor tendon reconstruction in 8 patients (10 digits) at a mean follow-up time
      of 3.8 years for neglected or failed primary repair of zone 2 lacerations and for
      neglected flexor digitorum profundus avulsions. The flexor digitorum longus to
      the second toe was used as the donor tendon graft. Four patients (4 digits)
      underwent single-stage reconstruction and 4 patients (6 digits) had multistage
      reconstruction. The overall patient satisfaction using a standardized visual
      analog reporting scale was excellent. There was 1 excellent, 1 good, 1 fair, and
      1 poor result in the single-stage reconstruction group, including 1 repair site
      rupture and 1 digit requiring tenolysis. In the multistage reconstruction group
      there was 1 excellent, 3 good, 1 fair, and no poor results, including 1 digit
      requiring tenolysis. One patient was lost to follow-up. There was no donor site
      morbidity. The average active motion recovery was 64% and 56% for single-stage
      and multistage reconstructions, respectively, and was 73% overall for single
      digit reconstructions. The results of this pilot study suggest that intrasynovial
      tendon grafting may offer an improved alternative for tendon grafting to the
      synovial spaces of the digit.

PMID- 10913216
TI  - The effects of hypothyroidism and thyroid replacement on the development of
      carpal tunnel syndrome.
AB  - Hypothyroidism is commonly included as an important risk factor for carpal tunnel
      syndrome (CTS), yet no study clearly defines the nature of this association. The
      purpose of this study was to evaluate the relationship between hypothyroidism and
      CTS in a controlled study. Twenty-six hypothyroid patients (45 hands) meeting our
      inclusion criteria with a diagnosis of primary hypothyroidism were questioned
      regarding date of diagnosis of hypothyroidism, duration and dose of thyroid
      replacement, and the presence, character, and duration of CTS symptoms. Twenty
      four healthy volunteers (47 hands) were used as controls. Clinical examination
      included sensibility testing with Semmes-Weinstein monofilaments, Weber 2-point
      discrimination testing, examining for thenar muscle atrophy and weakness,
      Phalen's test, Tinel's sign at the wrist, and the manual compression test.
      Electrodiagnostic testing including distal motor latency and distal sensory
      latency was performed on the median nerve at the wrist on all subjects. Nineteen
      patients (73%; 31 hands [68%]) displayed symptoms of CTS; of these, 16 patients
      (25 hands) had clinical examinations consistent with CTS. Only 6 of the 16
      patients with clinical CTS (7 of 25 hands) had electrical studies that supported
      a diagnosis of CTS. All these symptomatic patients were biochemically euthyroid.
      All control subjects had normal electrical study results and normal sensibility
      testing. Two subjects had positive clinical examinations, giving a false-positive
      rate of 4%. Carpal tunnel syndrome symptoms are common in hypothyroid patients
      even when they are euthyroid. In this group of patients, normal median nerve
      latencies at the wrist in the presence of CTS symptoms and a positive physical
      examination are more prevalent than expected by the reported sensitivities of
      electrodiagnostic testing. Standards for assessing normal median nerve latencies
      may be significantly different in hypothyroid patients.

PMID- 10913217
TI  - Ulnar nerve compression by an anomalous muscle following carpal tunnel release: a
      case report.
AB  - We describe the acute development of ulnar nerve compression following carpal
      tunnel release in a patient with an accessory palmaris longus muscle. Although
      anomalous muscles in the wrist are relatively common and may produce ulnar nerve
      compression, this particular occurrence following carpal tunnel release has not
      been previously described in the literature. We theorize that the compression of
      the ulnar nerve proximal to Guyon's canal was caused by increased tension along
      the long axis of the anomalous accessory palmaris longus muscle as a consequence
      of transverse carpal ligament division.

PMID- 10913218
TI  - The recurrence of deformity after surgical centralization for radial clubhand.
AB  - Fourteen children representing 19 cases of radial clubhand had centralization of
      the carpus on the distal ulna during an 18-year period. Age at the time of the
      initial surgery averaged 3.2 years (range, 0.7-8.1 years) and the follow-up
      periods averaged 6.5 years (range, 1.5-22.2 years). There were 16 type IV radial
      and 3 type III clubhands. Preoperative, postoperative, and follow-up x-rays were
      used to determine the initial deformity, amount of surgical correction, and
      degree of recurrence. The total angulation (the combination of the radial
      deviation of the hand and the ulna bow) was measured. The average preoperative
      angulation measured 83 degrees (range, 55 degrees to 110 degrees ).
      Centralization corrected the angulation an average of 58 degrees (range, 15
      degrees to 95 degrees ) to an average immediate postoperative total angulation of
      25 degrees (range, 5 degrees to 60 degrees ). At the final follow-up examination
      there was a loss of 38 degrees (range, 5 degrees to 105 degrees ) and the total
      angulation increased to an average of 63 degrees (range, 20 degrees to 120
      degrees ). The difference between the preoperative, postoperative, and follow-up
      angles was statistically significant. There was a significant correlation between
      the preoperative angle and the final angle, the preoperative angle and the amount
      of correction, the amount of correction obtained at surgery and the recurrence of
      the deformity, and the age at time of initial surgery and the amount of
      recurrence.

PMID- 10913219
TI  - Quantitative abductor pollicis brevis strength testing: reliability and normative
      values.
AB  - We conducted this study to establish reliability and normative values for
      abductor pollicis brevis strength. A portable microprocessor-controlled hand-held
      device was used for testing. Twelve healthy subjects were used for intrarater and
      interrater reliability testing. Intraclass correlation coefficients were 0.92 for
      intrarater testing and 0.89 for interrater reliability. Normative values for
      abductor pollicis brevis strength are presented by gender and age from the test
      results of 297 volunteers (121 men and 176 women; age range, 20-59 years) with at
      least 30 subjects in each subgroup. Abductor pollicis brevis strength was
      significantly greater in the men than in the women in all age groups. No
      significant differences were found related to age, side, or dominance. The
      results suggest that quantitative muscle testing produces consistent values for
      abductor pollicis brevis strength that remain fairly constant in patients aged 20
      to 59 years.

PMID- 10913220
TI  - Community acquired methicillin-resistant Staphylococcus aureus hand infections:
      case reports and clinical implications.
AB  - We report a series of 4 cases of community acquired methicillin-resistant
      Staphylococcus aureus hand infections in patients without risk factors.
      Methicillin-resistant S aureus infections commonly involve the skin and soft
      tissue; therefore, hand infections may become more common as the prevalence of
      this pathogen increases. Hand surgeons must be aware of this emerging pathogen
      and obtain appropriate tissue cultures to diagnose and effectively treat this
      infection.

PMID- 10913221
TI  - Upper extremity injection of household insecticide: a report of five cases.
AB  - Self-injection of household insecticide into the upper extremity in 5 patients is
      reported. All patients had mental problems, such as depression, substance abuse,
      or both. Four of the 5 cases were suicide attempts. Household insecticides can be
      divided into 3 categories based on the main chemical component. The hydrocarbon
      vehicle used in these insecticides, however, is poorly cleared by the local
      tissues and is responsible for fever, leukocytosis, and liquifaction necrosis.
      The focus for the hand surgeon is recognition and early and frequently repeated
      debridement. Psychiatric treatment and hand therapy are required.

PMID- 10913222
TI  - Multiple epidermal inclusion cysts in a patient with rheumatoid arthritis: a case
      report.
AB  - A construction worker with rheumatoid arthritis presented with multiple soft
      tissue masses on the volar surface of the palm and digits. A misdiagnosis of
      rheumatoid nodules was made secondary to the patient's history of rheumatoid
      arthritis. Subsequent excision confirmed multiple epidermal inclusion cysts,
      which was not entertained in the preoperative differential diagnosis. Follow-up
      evaluation 3 years later revealed no evidence of local recurrence. Based on our
      literature review, multiple epidermal inclusion cysts is a rare entity and has
      not been reported in a patient with rheumatoid arthritis.

PMID- 10913223
TI  - Recurrent myxoma of the hand.
AB  - Myxoma is a rare benign tumor composed of stellate or spindle-shaped cells in a
      loose myxoid stroma. Few cases involving the hand have previously been described.
      We present a rare case of recurrent myxoma in the intermetacarpal space and
      detail the clinical behavior of this indolent tumor.

PMID- 10913224
TI  - Does alpha-linolenic acid in combination with linoleic acid influence liver
      metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in
      Syrian hamsters?
AB  - Some fatty acids are reported to inhibit tumor growth of pancreatic carcinoma.
      However, it is still unknown if alpha-linolenic acid (ALA) and linoleic acid (LA)
      inhibit liver metastasis of ductal pancreatic adenocarcinoma. Therefore we
      studied the effect of these fatty acids on liver metastasis in the animal model
      of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic adenocarcinoma in
      Syrian hamsters. Since lipid peroxidation seems to be involved in carcinogenesis
      and metastasis, we further analyzed the intrahepatic concentration of
      thiobarbituric acid-reactive substances (TBARS) and activity of glutathione
      peroxidase (GSH-Px) and superoxide dismutase (SOD). We observed an increase in
      the incidence and the number of liver metastases in response to the combination
      of ALA and LA. This was accompanied by a decrease in hepatic GSH-Px activity and
      an increase in hepatic SOD activity and TBARS concentration. The increase in
      hepatic lipid peroxidation seems to be one possible mechanism of increasing liver
      metastasis in this study.

PMID- 10913225
TI  - Effect of supplementation of arachidonic acid (AA) or a combination of AA plus
      docosahexaenoic acid on breastmilk fatty acid composition.
AB  - We investigated whether supplementation with arachidonic acid (20:4 omega 6; AA),
      or a combination of AA and docosahexaenoic acid (22:6 omega 3; DHA) would affect
      human milk polyunsaturated fatty acid (PUFA) composition. Ten women were daily
      supplemented with 300 mg AA, eight with 300 mg AA, 110 mg eicosapentaenoic acid
      (20:5 omega 3; EPA) and 400 mg DHA, for one week and eight women served as
      unsupplemented controls. Milk samples were collected on days 0, 1 and 7. The
      fatty acid composition of the milk was analyzed by capillary gas chromatography
      with flame ionisation detection. Supplementation with AA alone had no effect on
      breastmilk AA, but tended to reduce EPA and DHA levels. Administration of a
      combination of AA, EPA and DHA tended to increase both milk AA and long chain
      PUFA (LCPUFA)omega 3 content. A larger simultaneous increase of milk AA, DHA and
      EPA than observed in the present study can probably be accomplished by the use of
      a combination of a lower LCPUFA omega 6/LCPUFA omega 3 ratio and higher AA, EPA
      and DHA dosages.

PMID- 10913226
TI  - Preferential distribution of long chain polyunsaturated fatty acids in
      phospatidyl ethanolamine fraction of guinea pig alveolar apical membranes.
AB  - We investigated the fatty acid distribution in guinea pig alveolar apical
      membranes at different developmental stages. Fatty acid composition of the
      purified membranes isolated from guinea pig fetuses (at 65 day, term=68 day),
      neonates (day 1) and adult males was determined. The levels of arachidonic acid
      (AA) and docosahexaenoic acid (DHA) were higher in the adult guinea pig alveolar
      apical membrane phosphatidylethanolamine (PE) fraction (9. 3+/-2.2 and 2.9+/
      1.0%, respectively) while in other phospholipids (PL) fractions their levels were
      low or absent (P<0.01). Furthermore, levels of AA and DHA in the PE fraction of
      apical membrane increased significantly from fetal (6.6+/-3.0 and 0.8+/-0.4%,
      respectively) to neonatal life (10.3+/-1.5 and 3.0+/-0.8%, respectively).
      Increase in the level of DHA (almost four-fold) was much more pronounced than
      that of AA (P<0.05). As for guinea pig alveolar membranes, EPA and AA were mostly
      present in the PE fraction in pulmonary adenocarcinoma derived cells (A549
      cells), a parallel model of type II pneumocytes, with the levels of AA around
      three-fold greater than that of EPA, Binding of radiolabelled fatty acids to A549
      cells showed no significant differences between the maximum uptake achieved for
      different fatty acids (AA, 1.7+/-0.2, EPA, 2.3+/-0.3, LA, 1.7+/-0.2, OA, 2.0+/
      0.2nmol/mg protein, P>0.5). Once the fatty acids were taken up by these cells AA
      was mostly identifiable in the monoacylglycerol (MAG) fraction, whereas EPA was
      equally distributed between the MAG and PL fractions. Oleic acid was mainly
      present in the triglyceride (TAG) fraction whereas LA was evenly distributed
      between the TAG, MAG, and PL fractions. Our data demonstrate a preferential
      distribution of AA and DHA in PE fractions of alveolar apical membranes during
      development.

PMID- 10913227
TI  - The effect of granulocyte macrophage-colony stimulating factor on the
      prostaglandin E(2)-like activity of the small intestine of rat during total body
      irradiation.
AB  - Radiation-induced gastrointestinal toxicity is important for subjects receiving
      radiation to the pelvis. Eicosanoids and free radicals may be involved in the
      mechanism. rHuGM-CSF is a subcutaneously administered drug which may reduce some
      side effects of radiation. This experimental study was undertaken to determine
      the effectiveness of rHuGM-CSF on PGE(2)-like activity of the small intestine in
      rats. Thirty-two adult male Wistar-Albino rats entered the study to be randomized
      to one of the four groups: Group I. Control; II. Drug administered; III.
      Irradiated; IV. Irradiated and drug administered. Radiation was by total body
      irradiation, 800 rads with Cobalt 60. On the 9th day the animals were killed and
      biopsies were taken from the terminal ileum. PGE(2)-like activity was evaluated.
      Animals were weighed on the day of irradiation and end of the experiment. A
      statistically significant difference was found according to pre- and post
      treatment weights in the irradiated and nonirradiated drug administered groups
      (Groups II and IV) (P=0.035 and 0.018, respectively). PGE(2)-like activity in the
      intestinal tissue was statistically significant higher in the drug-treated
      animals, both in non-irradiated and irradiated groups. Surprisingly, irradiation
      was found to decrease the PGE(2)-like activity in the intestinal tissue
      (P=0.008). rHuGM-CSF was found to increase PGE(2)-like activity in the intestinal
      tissue. The cellular mechanisms underlying this must be clearly determined and
      weighed carefully in considering the drug for clinical usage.

PMID- 10913228
TI  - Sphingosine 1-phosphate amplifies phosphoinositide hydrolysis stimulated by
      prostaglandin f2 alpha in osteoblasts: involvement of p38MAP kinase.
AB  - We previously showed that sphingosine 1-phosphate phosphorylates p42/p44 mitogen
      activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1
      cells. In the present study, we investigated the effect of sphingosine 1
      phosphate on phospholipase C-catalyzing phosphoinositide hydrolysis induced by
      prostaglandin F2alpha (PGF2 alpha) in these cells. Sphingosine 1-phosphate
      significantly amplified the inositol phosphates formation by PGF2 alpha.
      Sphingosine 1-phosphate did not enhance the formation induced by NaF, a direct
      activator of heterotrimeric GTP-binding proteins. PD98059, an inhibitor of the
      kinase that activates p42/p44 MAP kinase, had little effect on the amplification
      by sphingosine 1-phosphate. SB203580, an inhibitor of p38 MAP kinase, reduced the
      effect of sphingosine 1-phosphate on the formation of inositol phosphates by PGF2
      alpha. The phosphorylation of p42/p44 MAP kinase by PGF alpha was attenuated by
      PD98059. SB203580 suppressed the phosphorylation of p38 MAP kinase by PGF2 alpha.
      Tumor necrosis factor-alpha enhanced the PGF2 alpha-stimulated formation of
      inositol phosphates. These results strongly suggest that sphingosine 1-phosphate
      amplifies PGF2 alpha-induced phosphoinositide hydrolysis by phospholipase C
      through p38 MAP kinase in osteoblasts.

PMID- 10913229
TI  - Involvement of LTD(4)in allergic pulmonary inflammation in mice: modulation by
      cysLT(1)antagonist MK-571.
AB  - Cysteinyl leukotrienes are potent inflammatory molecules playing a major role in
      asthma. The involvement of these mediators in hypersensitivity in mice is not
      well known. This study aimed at elucidating their implication by using MK-571, a
      cysLT(1)receptor antagonist. Mice were sensitized with a suspension of ovalbumin
      (8 microg) adsorbed to alum (2 mg) and were challenged with an aerosolized
      ovalbumin solution (0.5%). Inflammatory cell infiltration in the bronchoalveolar
      lavage (mostly eosinophils) following antigen challenge was inhibited by
      dexamethasone (0.1, 1 and 5 mg kg(-1)s.c.) and MK-571 (1, 10, 100 mg kg(-1)i.v.)
      in a dose-dependent manner. Maximal inhibition was 95% with 5 mg kg(
      1)dexamethasone and 90% with 100 mg kg(-1)MK-571. When injected together they
      showed an additive inhibitory effect on eosinophil infiltration. Bronchial
      hyperreactivity, measured by the increased pulmonary insufflation pressure to
      carbachol injections, was also inhibited dose-dependently by MK-571. The
      EC(50)values for carbachol were of 22.39+/-1.12 microg kg(-1)in sensitized and
      challenged animals that did not receive MK-571 and increased to 43.65+/-1.10,
      50.12+/-1.15 and 83.18+/-1.16 microg kg(-1)in animals treated with 1, 10 and 100
      mg kg(-1)MK-571 respectively. Lung microvascular leakage (as measured by Evans
      blue extravasation) induced by antigen bronchoprovocation was reduced by 22%
      after treatment with 10 mg kg(-1)MK-571. All these inhibitory effects of MK-571
      suggest a role for leukotriene D(4)in this animal model of allergic asthma.

PMID- 10913230
TI  - Nitric oxide enhances PGI(2)production by human pulmonary artery smooth muscle
      cells.
AB  - To evaluate the effect of exogenous nitric oxide (NO) and endogenous NO on the
      production of prostacyclin (PGI(2)) by cultured human pulmonary artery smooth
      muscle cells (HPASMC) treated with lipopolysaccharide (LPS), interleukin
      1(beta)(IL-1(beta)), tumor necrosis factor alpha (TNF(alpha)) or interferon gamma
      (IFN(gamma)), HPASMC were treated with LPS and cytokines together with or without
      sodium nitroprusside (SNP), NO donor, N(G)-monomethyl-L-arginine (L-NMMA), NO
      synthetase inhibitor, and methylene blue (MeB), an inhibitor of the soluble
      guanylate cyclase. After incubation for 24 h, the postculture media were
      collected for the assay of nitrite by chemiluminescence method and the assay of
      PGI(2)by radioimmunoassay. The incubation of HPASMC with various concentrations
      of LPS, IL-1(beta)or TNF(alpha)for 24 h caused a significant increase in nitrite
      release and PGI(2)production. However, IFN(gamma)slightly increased the release
      of nitrite and had little effect on PGI(2)production. Although the incubation of
      these cells for 24 h with SNP did not cause a significant increase in
      PGI(2)production, the incubation of HPASMC with SNP and 10 microg/ml LPS, or with
      SNP and 100 U/ml IL-1(beta)further increase PGI(2)production and this enhancement
      was closely related to the concentration of SNP. However, stimulatory effect of
      SNP on PGI(2)production was not found in TNF(alpha)- and IFN(gamma)- treated
      HPASMC. Addition of L-NMMA to a medium containing LPS or IL-1(beta)reduced
      nitrite release and attenuated the stimulatory effect of those agents on
      PGI(2)production. MeB significantly suppressed the production of PGI(2)by HPASMC
      treated with or without LPS or IL-1(beta). The addition of SNP partly reversed
      the inhibitory effect of MeB on PGI(2)production by HPASMC. These experimental
      results suggest that NO might stimulate PGI(2)production by HPASMC. Exogenous NO
      together with endogenous NO induced by LPS or cytokines from smooth muscle cells
      might synergetically enhance PGI(2)production by these cells, possibly in
      clinical disorders such as sepsis and acute respiratory distress syndrome.

PMID- 10913231
TI  - Changes in n-6 and n-3 polyunsaturated fatty acids during lipid-peroxidation of
      mitochondria obtained from rat liver and several brain regions: effect of alpha
      tocopherol.
AB  - The effect of intraperitoneal administration of alpha-tocopherol (100 mg/kg
      weight/24 h) on ascorbate (0-0.4 mM) induced lipid peroxidation of mitochondria
      isolated from rat liver, cerebral hemispheres, brain stem and cerebellum was
      examined. The ascorbate induced light emission in hepatic mitochondria was nearly
      completely inhibited by alpha-tocopherol (control-group: 114.32+/-14.4; vitamin E
      group: 17.45+/-2.84, c.p.m.x10(-4)). In brain mitochondria, 0.2 mM ascorbate
      produced the maximal chemiluminescence and significant differences among both
      groups were not observed. No significant differences in the chemiluminescence
      values between control and vitamin E treated groups were observed when the three
      brain regions were compared. The light emission produced by mitochondrial
      preparations was much higher in cerebral hemispheres than in brain stem and
      cerebellum. In liver and brain mitochondria from control group, the level of
      arachidonic acid (C20:4n6) and docosahexaenoic acid (C22:6n3) was profoundly
      affected. Docosahexaenoic in liver mitochondria from vitamin E group decreased by
      30% upon treatment with ascorbic acid when compared with mitochondria lacking
      ascorbic acid. As a consequence of vitamin E treatment, a significant increase of
      C22:6n3 was detected in rat liver mitochondria (control-group: 6.42 +/-0.12;
      vitamin E-group: 10.52 +/-0.46). Ratios of the alpha-tocopherol concentrations in
      mitochondria from rats receiving vitamin E to those of control rats were as
      follows: liver, 7.79; cerebral hemispheres, 0.81; brain stem, 0.95; cerebellum,
      1.05. In liver mitochondria, vitamin E shows a protector effect on oxidative
      damage. In addition, vitamin E concentration can be increased in hepatic but not
      in brain mitochondria. Lipid peroxidation mainly affected, arachidonic (C20:4n6)
      and docosahexaenoic (C22:6n3) acids.

PMID- 10913232
TI  - H-densities: a new concept for hydrated molecules.
AB  - It is common to represent molecules by "ball-and-stick" models that represent
      static positions of atoms. However, the vibrational states of water molecules
      involved in hydrogen bonding have wide amplitudes, even in their ground states.
      Here we introduce a new representation of this wide-amplitude vibrational motion:
      H-density plots. These plots represent the delocalized zero-point vibrational
      motion of terminal hydrogen atoms of water molecules weakly bound to other
      molecules. They are a vibrational analogy to electron densities. Calculations of
      the H-densities for complexes of water with water, benzene, phenol, and DNA bases
      are presented. These are obtained using the quantum diffusion Monte Carlo method.
      Comparisons of measured and calculated rotational constants provide experimental
      evidence of the new concept.

PMID- 10913233
TI  - Hypersensitive radical probes and the mechanisms of cytochrome P450-catalyzed
      hydroxylation reactions.
AB  - The title probes are precursors to kinetically calibrated, aryl-substituted
      cyclopropylcarbinyl radicals that rearrange with picosecond lifetimes.
      Applications in studies of cytochrome P450-catalyzed hydroxylation reactions are
      reviewed. Initially confusing results regarding lifetimes of radicals in the
      hydroxylation reactions were resolved when second-generation probes that
      distinguish between radicals and cations were employed. The results indicate that
      two electrophilic oxidizing species are involved in P450-catalyzed
      hydroxylations, an iron-oxo species that inserts oxygen and a hydroperoxo-iron
      species that inserts OH(+). The cationic rearrangement products are ascribed to
      reactions of the protonated alcohol products formed from the latter.

PMID- 10913235
TI  - Nickel-catalyzed cyclizations, couplings, and cycloadditions involving three
      reactive components.
AB  - Transition-metal-catalyzed processes that allow the efficient coupling of three
      reactive components in a chemoselective and stereoselective fashion are
      particularly useful in the synthesis of complex organic molecules from simple,
      readily available substrates. This account outlines work primarily from the
      author's laboratory on the development of nickel-catalyzed multicomponent
      coupling processes. An overview of new synthetic methods, a discussion of
      potential mechanisms, and a description of applications in complex-molecule
      synthesis are provided.

PMID- 10913234
TI  - Nanofabrication of self-assembled monolayers using scanning probe lithography.
AB  - This Account focuses on our recent and systematic effort in the development of
      generic scanning probe lithography (SPL)-based methodologies to produce
      nanopatterns of self-assembled monolayers (SAMs). The key to achieving high
      spatial precision is to keep the tip-surface interactions strong and local. The
      approaches used include two AFM-based methods, nanoshaving and nanografting,
      which rely on the local force, and two STM-based techniques, electron-induced
      diffusion and desorption, which use tunneling electrons for fabrication. In this
      Account we discuss the principle of these procedures and the critical steps in
      controlling local tip-surface interactions. The advantages of SPL will be
      illustrated through various examples of production and modification of SAM
      nanopatterns and their potential applications.

PMID- 10913236
TI  - A dynamic view of self-assembled monolayers.
AB  - In this Account, we discuss the dynamic features of self-assembled monolayers
      (SAMs) on both planar and nonplanar substrates. Our focus is on organothiol and
      organic acid-based monolayers. Results from variable-temperature electrochemical,
      calorimetric, vibrational, and solid-state NMR spectroscopic measurements lead to
      a convergent description of SAM dynamics.

PMID- 10913237
TI  - The whole story of the two-electron bond, with the delta bond as a paradigm.
AB  - It is shown that the delta bond, as found particularly in the Re(2)(6+) and
      Mo(2)(4+) cores of hundreds of compounds, provides a paradigm for the behavior of
      two-electron bonds of all types. By control of the angle of twist around the M-M
      axis, the strength of the bond can be systematically varied. By means of
      conventional electronic spectroscopy, nuclear magnetic resonance spectroscopy,
      and two-photon excitation spectroscopy, the entire picture of the manifold of
      four states for two electrons bonding two atoms, as first described by Coulson
      and Fischer in 1949, has been confirmed.

PMID- 10913238
TI  - Raising flags: applications of chemical marker groups to study self-assembly,
      chirality, and orientation of interfacial films by scanning tunneling microscopy.
AB  - When used in conjunction with "chemical marker groups" (functionalities such as 
      Br and -COOH), scanning tunneling microscopy is a powerful tool for studying the
      properties of liquid-solid interfaces. Chemical markers serve as "flags" for the
      identification of interfacial structures, allowing, for example, the absolute
      chirality of optically active molecules self-assembling on a graphite surface to
      be determined. Subtle changes in the orientation of these chemical
      functionalities that affect the long-range order of interfacial films have also
      been observed and explored. Finally, alterations in self-assembly resulting from
      variations in adsorbate or substrate structure can be deduced by taking advantage
      of these STM "flags".

PMID- 10913239
TI  - Elucidating a biological role for chromium at a molecular level.
AB  - Chromium is an essential trace element for mammals and is required for
      maintenance of proper carbohydrate and lipid metabolism. However, elucidating its
      function at a molecular level has proved to be problematic. Recent research has
      revealed that the chromium-binding oligopeptide chromodulin may play a unique
      role in the autoamplification of insulin signaling. Attempts to develop chromium
      containing nutritional supplements and therapeutics are described.

PMID- 10913240
TI  - Action of antimicrobial peptides: two-state model.
AB  - The argument and experimental evidence are presented for a two-state model that
      explains the action of both helical and beta-sheet antimicrobial peptides after
      they bind to the plasma membranes of cells. Each peptide has two distinct
      physical states of binding to lipid bilayers. At low peptide-to-lipid ratios
      (P/L), the peptide tends to adsorb in the lipid headgroup region in a
      functionally inactive state. At a P/L above a threshold value P/L, the peptide
      forms a multiple-pore state that is lethal to a cell. The susceptibility of a
      cell to an antimicrobial peptide depends on the value of P/L that is determined
      by the lipid composition of the cell membrane. This model provides plausible
      explanations for the experimental findings that the susceptibility of different
      bacteria to a peptide is not directly correlated to its binding affinity,
      different peptides preferentially kill different pathogens, and peptides exhibit
      varying levels of lytic activity against different eukaryotic cells.

PMID- 10913241
TI  - Electrochromic detection of a coherent component in the formation of the charge
      pair P(+)H(L)(-) in bacterial reaction centers.
AB  - We demonstrate coupling of an intraprotein electron transfer reaction to coherent
      vibrational motions. The kinetics of charge separation toward the radical pair
      state P(+)H(L)(-) were studied in reaction centers of Rhodobacter sphaeroides at
      15 K. The electrochromic shift of the bacteriochlorophyll monomers is the most
      prominent spectral feature associated with this charge displacement. The newly
      reported absolute absorption spectrum of the P(+)H(L)(-) state is discussed in
      terms of this shift. In wild-type reaction centers, the rise kinetics of the
      electrochromic shift display a small but significant 30 cm(-)(1) periodic
      modulation (period of approximately 1 ps). This modulation is also present in
      FL181Y mutant reaction centers, where overall charge separation is somewhat more
      rapid than in the wild-type reaction center. In contrast, in YM210L mutant
      reaction centers, where the charge separation is much slower, the modulation is
      absent. The conclusion that the motion along the reaction coordinate has a 30 cm(
      )(1) coherent component is discussed in light of possible mechanisms of electron
      transfer.

PMID- 10913242
TI  - Involvement of electrostatic interactions in the mechanism of peptide folding
      induced by sodium dodecyl sulfate binding.
AB  - Sodium dodecyl sulfate (SDS) has consistently been shown to induce secondary
      structure, particularly alpha-helices, in polypeptides, and is commonly used to
      model membrane and other hydrophobic environments. However, the precise mechanism
      by which SDS induces these conformational changes remains unclear. To examine the
      role of electrostatic interactions in this mechanism, we have designed two
      hydrophilic, charged amphipathic alpha-helical peptides, one basic
      (QAPAYKKAAKKLAES) and the other acidic (QAPAYEEAAEELAKS), and their structures
      were studied by CD and NMR. The design of the peptides is based on the sequence
      of the segment of residues 56-70 of human platelet factor 4 [PF4(56-70),
      QAPLYKKIIKKLLES]. Both peptides were unstructured in water, and in the presence
      of neutral, zwitterionic, or cationic detergents. However, in SDS at neutral pH,
      the basic peptide folded into an alpha-helix. By contrast, the pH needed to be
      lowered to 1.8 before alpha-helix formation was observed for the acidic peptide.
      Strong, attractive electrostatic interactions, between the anionic groups of SDS
      and the cationic groups of the lysines, appeared to be necessary to initiate the
      folding of the basic peptide. NMR analysis showed that the basic peptide was
      fully embedded in SDS-peptide micelles, and that its three-dimensional alpha
      helical structure could be superimposed on that of the native structure of PF4(56
      70). These results enabled us to propose a working model of the basic peptide-SDS
      complex, and a mechanism for SDS-induced alpha-helical folding. This study
      demonstrates that, while the folding of peptides is mostly driven by hydrophobic
      effects, electrostatic interactions play a significant role in the formation and
      the stabilization of SDS-induced structure.

PMID- 10913243
TI  - Interface characterization of the type II module pair from fibronectin.
AB  - The lone (1)F2(2)F2 modular pair of fibronectin is found in the collagen-binding
      region. This exclusive localization suggests the (1)F2(2)F2 pair plays an
      important role in the recognition of collagen. However, no information is
      currently available about the interaction between the two F2 modules and, thus,
      the orientation of their putative collagen-binding sites with respect to one
      another. Comparison of a variety of high-resolution NMR parameters from the F2
      modules in isolation and the (1)F2(2)F2 pair was used to establish the extent of
      interaction between the F2 modules in the pair. Chemical shifts of the F2 modules
      and the (1)F2(2)F2 pair indicate that the structures of the modules are preserved
      in the pair and that, with the exception of the covalent linkage, they do not
      interact. (15)N NMR relaxation data identify significant motion occurring in the
      linker region of the (1)F2(2)F2 pair, and analyses of the anisotropic diffusion
      properties of the (1)F2(2)F2 pair are consistent with the modules in the F2 pair
      tumbling independent of one another.

PMID- 10913244
TI  - NMR solution structure and receptor peptide binding of the CC chemokine eotaxin
      2.
AB  - The human CC chemokine eotaxin-2 is a specific agonist for the chemokine receptor
      CCR3 and may play a role in the recruitment of eosinophils in allergic diseases
      and parasitic infections. We report the solution structure of eotaxin-2
      determined using heteronuclear and triple resonance NMR methods. A family of 20
      structures was calculated by hybrid distance geometry-simulated annealing from
      854 NOE distance restraints, 48 dihedral angle restraints, and 12 hydrogen bond
      restraints. The structure of eotaxin-2 (73 amino acid residues) consists of a
      helical turn (residues 17-20) followed by a 3-stranded antiparallel beta-sheet
      (residues 22-26, 37-41, and 44-49) and an alpha-helix (residues 54-66). The N
      loop (residues 9-16) is packed against both the sheet and the helix with the two
      conserved disulfide bonds tethering the N-terminal/N-loop region to the beta
      sheet. The average backbone and heavy atom rmsd values of the 20 structures
      (residues 7-66) are 0.52 and 1.13 A, respectively. A linear peptide corresponding
      to the N-terminal region of CCR3 binds to eotaxin-2, inducing concentration
      dependent chemical shift changes or line broadening of many residues. The
      distribution of these residues suggests that the peptide binds into an extended
      groove located at the interface between the N-loop and the beta2-beta3 hairpin.
      The receptor peptide may also interact with the N-terminus of the chemokine and
      part of the alpha-helix. Comparison of the eotaxin-2 structure with those of
      related chemokines indicates several structural features that may contribute to
      receptor specificity.

PMID- 10913245
TI  - Crystal structures of spin labeled T4 lysozyme mutants: implications for the
      interpretation of EPR spectra in terms of structure.
AB  - High resolution (1.43-1.8 A) crystal structures and the corresponding electron
      paramagnetic resonance (EPR) spectra were determined for T4 lysozyme derivatives
      with a disulfide-linked nitroxide side chain [-CH(2)-S-S-CH(2)-(3-[2,2,5,5
      tetramethyl pyrroline-1-oxyl]) identical with R1] substituted at solvent-exposed
      helix surface sites (Lys65, Arg80, Arg119) or a tertiary contact site (Val75). In
      each case, electron density is clearly resolved for the disulfide group,
      revealing distinct rotamers of the side chain, defined by the dihedral angles
      X(1) and X(2). The electron density associated with the nitroxide ring in the
      different mutants is inversely correlated with its mobility determined from the
      EPR spectrum. Residue 80R1 assumes a single g(+)()g(+)() conformation (Chi(1) =
      286, X(2) = 294). Residue 119R1 has two EPR spectral components, apparently
      corresponding to two rotamers, one similar to that for 80R1 and the other in a
      tg(-)() conformation (Chi(1) = 175, X(2) = 54). The latter state is apparently
      stabilized by interaction of the disulfide with a Gln at i + 4, a situation also
      observed at 65R1. R1 residues at helix surface site 65 and tertiary contact site
      75 make intra- as well as intermolecular contacts in the crystal and serve to
      identify the kind of molecular interactions possible for the R1 side chain. A
      single conformation of the entire 75R1 side chain is stabilized by a variety of
      interactions with the nitroxide ring, including hydrophobic contacts and two
      unconventional C-H.O hydrogen bonds, one in which the nitroxide acts as a donor
      (with tyrosine) and the other in which it acts as an acceptor (with
      phenylalanine). The interactions revealed in these structures provide an
      important link between the dynamics of the R1 side chain, reflected in the EPR
      spectrum, and local protein structure. A library of such interactions will
      provide a basis for the quantitative interpretation of EPR spectra in terms of
      protein structure and dynamics.

PMID- 10913246
TI  - Preferential oxidation of zinc finger 2 in estrogen receptor DNA-binding domain
      prevents dimerization and, hence, DNA binding.
AB  - For approximately one-third of estrogen receptor (ER)-positive breast cancer
      patients, extracted tumor ER is unable to bind to its cognate DNA estrogen
      response element (ERE), an effect that is partly reversible by the thiol-reducing
      agent dithiothreitol (DTT). Full-length (67 kDa) ER or its 11 kDa recombinant DNA
      binding domain (ER-DBD) is also susceptible to loss of structure and function by
      the action of oxidants such as diamide and hydrogen peroxide; however, prior DNA
      binding by ER or ER-DBD protects against this oxidant induced loss of function.
      The ER-DBD contains two (Cys)(4)-liganded zinc finger motifs that cooperate to
      stabilize a rigid DNA-binding recognition helix and a flexible helix-supported
      dimerization loop, respectively. Comparisons between synthetic peptide analogues
      of each zinc finger and recombinant ER-DBD in the presence of zinc by
      electrophoretic mobility shift assay, circular dichroism, and mass spectrometry
      confirm that cooperativity between these zinc fingers is required for both ER-DBD
      structure (alpha-helicity) and function (dimeric DNA binding). Rapid proteolytic
      digestion of monomeric, non-DNA-bound ER-DBD followed by HPLC-MS analysis of the
      resulting peptides demonstrates that zinc inhibits thiol oxidation of the DNA
      binding finger, but not the finger supporting the flexible dimerization loop,
      which remains sensitive to internal disulfide formation. These findings indicate
      that the loss of ER DNA-binding function in extracts from some primary breast
      tumors and in ER or ER-DBD exposed to thiol-reacting oxidants results from this
      asymmetric zinc finger susceptibility to disulfide formation that prevents
      dimerization. Although ER-DBD contains several strategically located methionine
      residues, they are less susceptible to oxidation than the thiol groups and, thus,
      afford no protection against cysteine oxidation and consequent loss of ER DNA
      binding function.

PMID- 10913247
TI  - Active site of lysyl-tRNA synthetase: structural studies of the adenylation
      reaction.
AB  - Aminoacyl-tRNA synthetases play a key role in protein biosynthesis by catalyzing
      the specific aminoacylation of tRNA. The energy required for the formation of the
      ester bond between the amino acid carboxylate group and the tRNA acceptor stem is
      supplied by coupling the reaction to the hydrolysis of ATP. Lysyl-tRNA synthetase
      from Escherichia coli belongs to the family of class II synthetases and carries
      out a two-step reaction, in which lysine is activated by being attached to the
      alpha-phosphate of AMP before being transferred to the cognate tRNA. Crystals of
      the thermo-inducible E. coli lysyl-tRNA synthetase LysU which diffract to 2.1 A
      resolution have been used to determine crystal structures of the enzyme in the
      presence of lysine, the lysyl-adenylate intermediate, and the nonhydrolyzable ATP
      analogue AMP-PCP. Additional data have been obtained from crystals soaked in a
      solution containing ATP and Mn(2+). The refined crystal structures give
      "snapshots" of the active site corresponding to key steps in the aminoacylation
      reaction and provide the structural framework for understanding the mechanism of
      lysine activation. The active site of LysU is shaped to position the substrates
      for the nucleophilic attack of the lysine carboxylate on the ATP alpha-phosphate.
      No residues are directly involved in catalysis, but a number of highly conserved
      amino acids and three metal ions coordinate the substrates and stabilize the
      pentavalent transition state. A loop close to the catalytic pocket, disordered in
      the lysine-bound structure, becomes ordered upon adenine binding.

PMID- 10913249
TI  - Energetics of DNA intercalation reactions.
AB  - Isothermal titration calorimetry has been used to determine the binding enthalpy
      and heat capacity change (DeltaC(p)()) for a series of DNA intercalators,
      including ethidium, propidium, daunorubicin, and adriamycin. Temperature
      dependent binding enthalpies were measured directly for the ligands, from which
      DeltaC(p)() values of -140 to -160 cal mol(-)(1) K(-)(1) were calculated.
      Published van't Hoff plots were reanalyzed to obtain DeltaC(p)() values of -337
      to -423 cal mol(-)(1) K(-)(1) for the binding of actinomycin D to several DNA
      oligonucleotide duplexes with defined sequences. Heat capacity changes for DNA
      intercalation were found to correlate with the alterations in solvent-accessible
      surface area calculated from available high-resolution structural data. Multiple
      linear regression was used to derive the relationship DeltaC(p)() = 0. 382(+/
      0.026)DeltaA(np) - 0.121(+/-0.077)DeltaA(p) cal mol(-)(1) K(-)(1), where
      DeltaA(np) and DeltaA(p) are the binding-induced changes in nonpolar and polar
      solvent-accessible surface areas (in square angstroms), respectively. The
      DeltaC(p)() terms were used to estimate the hydrophobic contribution to
      intercalative binding free energies, yielding values that ranged from -11.2
      (ethidium) to -30 kcal mol(-)(1) (actinomycin D). An attempt was made to parse
      the observed binding free energies of ethidium and propidium into five underlying
      contributions. Such analysis showed that the DNA binding behavior of these simple
      intercalators is driven almost equally by hydrophobic effects and van der Waals
      contacts within the intercalation site.

PMID- 10913248
TI  - Stopped-flow fluorescence studies of HMG-domain protein binding to cisplatin
      modified DNA.
AB  - High-mobility group (HMG) domain proteins bind specifically to the major DNA
      adducts formed by the anticancer drug cisplatin and can modulate the biological
      response to this inorganic compound. Stopped-flow fluorescence studies were
      performed to investigate the kinetics of formation and dissociation of complexes
      between HMG-domain proteins and a series of 16-mer oligonucleotide probes
      containing both a 1,2-intrastrand d(GpG) cisplatin cross-link and a fluorescein
      modified deoxyuridine residue. Rate constants, activation parameters, and
      dissociation constants were determined for complexes formed by HMG1 domain A and
      the platinated DNA probes. The sequence context of the cisplatin adduct modulates
      the value of the associative rate constant for HMG1 domain A by a factor of 2-4,
      contributing significantly to differences in binding affinity. The rates of
      association or dissociation of the protein-DNA complex were similar for a 71 bp
      platinated DNA analogue. Additional kinetic studies performed with HMG1 domain B,
      an F37A domain A mutant, and the full-length HMG1 protein highlight differences
      in the binding properties of the HMG domains. The stopped-flow studies
      demonstrate the utility of the fluorescein-dU probe in studying protein-DNA
      complexes. The kinetic data will assist in determining what role these proteins
      might play in the cisplatin mechanism of action.

PMID- 10913250
TI  - Restricted motion of the lipoyl-lysine swinging arm in the pyruvate dehydrogenase
      complex of Escherichia coli.
AB  - The three lipoyl (E2plip) domains of the dihydrolipoyl acetyltransferase
      component of the pyruvate dehydrogenase (PDH) complex of Escherichia coli house
      the lipoyl-lysine side chain essential for active-site coupling and substrate
      channelling within the complex. The structure of the unlipoylated form of the
      innermost domain (E2plip(apo)) was determined by multidimensional NMR
      spectroscopy and found to resemble closely that of a nonfunctional hybrid domain
      determined previously [Green et al. (1995) J. Mol. Biol. 248, 328-343]. The
      domain comprises two four-stranded beta-sheets, with the target lysine residue
      residing at the tip of a type-I beta-turn in one of the sheets; the N- and C
      termini lie close together at the opposite end of the molecule in the other beta
      sheet. Measurement of (15)N NMR relaxation parameters and backbone
      hydrogen/deuterium (H/D) exchange rates reveals that the residues in and
      surrounding the lipoyl-lysine beta-turn in the E2plip(apo) form of the domain
      become less flexible after lipoylation of the lysine residue. This implies that
      the lipoyl-lysine side chain may not sample the full range of conformational
      space once thought. Moreover, reductive acetylation of the lipoylated domain
      (E2plip(holo) --> E2plip(redac)) was accompanied by large changes in chemical
      shift between the two forms, and multiple resonances were observed for several
      residues. This implies a change in conformation and the existence of multiple
      conformations of the domain on reductive acetylation, which may be important in
      stabilizing this catalytic intermediate.

PMID- 10913251
TI  - Structures of active and latent PAI-1: a possible stabilizing role for chloride
      ions.
AB  - Serpins exhibit a range of physiological roles and can contribute to certain
      disease states dependent on their various conformations. Understanding the
      mechanisms of the large-scale conformational reorganizations of serpins may lead
      to a better understanding of their roles in various cardiovascular diseases. We
      have studied the serpin, plasminogen activator inhibitor 1 (PAI-1), in both the
      active and the latent state and found that anionic halide ions may play a role in
      the active-to-latent structural transition. Crystallographic analysis of a stable
      mutant form of active PAI-1 identified an anion-binding site between the central
      beta-sheet and a small surface domain. A chloride ion was modeled in this site,
      and its identity was confirmed by soaking crystals in a bromide-containing
      solution and calculating a crystallographic difference map. The anion thus
      located forms a 4-fold ligated linchpin that tethers the surface domain to the
      central beta-sheet into which the reactive center loop must insert during the
      active-to-latent transition. Timecourse experiments measuring active PAI-1
      stability in the presence of various halide ions showed a clear trend for
      stabilization of the active form with F(-) > Cl(-) > Br(-) >> I(-). We propose
      that the "stickiness" of this pin (i.e., the electronegativity of the anion)
      contributes to the energetics of the active-to-latent transition in the PAI-1
      serpin.

PMID- 10913252
TI  - Structural analysis of the neuronal SNARE protein syntaxin-1A.
AB  - Intracellular trafficking depends on the docking and fusion of transport vesicles
      with cellular membranes. Central to docking and fusion is the pairing of SNARE
      proteins (soluble NSF attachment protein receptors) associated with the vesicle
      and target membranes (v- and t-SNAREs, respectively). Here, the X-ray structure
      of an N-terminal conserved domain of the neuronal t-SNARE syntaxin-1A was
      determined to a resolution of 1.9 A using multiwavelength anomalous diffraction.
      This X-ray structure, which is in general agreement with an NMR structure of a
      similar fragment, provides new insight into the interaction surface between the N
      terminal domain and the remainder of the protein. In vitro characterization of
      the intact cytoplasmic domain of syntaxin revealed that it forms dimers, and
      probably tetramers, at low micromolar concentrations, with concomitant structural
      changes that can be detected by limited proteolysis. These observations suggest
      that the promiscuity characteristic of pairing between v-SNAREs and t-SNAREs
      extends to the formation of homo-oligomeric t-SNARE complexes as well. They also
      suggest a potential role for the neuronal Sec1 protein (nSec1) in preventing the
      formation of syntaxin multimers.

PMID- 10913253
TI  - Myotonic dystrophy protein kinase domains mediate localization, oligomerization,
      novel catalytic activity, and autoinhibition.
AB  - Human myotonic dystrophy protein kinase (DMPK) is a member of a novel class of
      multidomain protein kinases that regulate cell size and shape in a variety of
      organisms. However, little is currently known about the general properties of
      DMPK including domain function, substrate specificity, and potential mechanisms
      of regulation. Two forms of the kinase are expressed in muscle, DMPK-1 and DMPK
      2. We demonstrate that the larger DMPK-1 form (the primary translation product)
      is proteolytically cleaved near the carboxy terminus to generate the smaller DMPK
      2 form. We further demonstrate that the coiled-coil domain is required for DMPK
      oligomerization; coiled-coil mediated oligomerization also correlated with
      enhanced catalytic activity. DMPK was found to exhibit a novel catalytic activity
      similar to, but distinct from, related protein kinases such as protein kinase C
      and A, and the Rho kinases. We observed that recombinant DMPK-1 exhibits low
      activity, whereas the activity of carboxy-terminally truncated DMPK is increased
      approximately 3-fold. The inhibitory activity of the full-length kinase was
      mapped to what appears to be a pseudosubstrate autoinhibitory domain at the
      extreme carboxy terminus of DMPK. To date, endogenous activators of DMPK are
      unknown; however, we observed that DMPK purified from cells exposed to the G
      protein activator GTP-gamma-S exhibited an approximately 2-fold increase in
      activity. These results suggest a general model of DMPK regulation with two main
      regulatory branches: short-term activation of the kinase in response to G protein
      second messengers and long-term activation as a result of proteolysis.

PMID- 10913254
TI  - Oligomerization of peptides analogous to the cytoplasmic domains of coatomer
      receptors revealed by mass spectrometry.
AB  - Members of the p24 family of type I transmembrane proteins are involved in
      budding of coat protein type I (COPI)-coated vesicles. They serve as coat protein
      receptors, binding via their cytoplasmic domains to coatomer, a stable cytosolic
      protein complex that represents the major coat component of these vesicles.
      Experimental evidence suggest that p23, a member of the p24 family, binds to
      coatomer in an oligomeric state and that this binding triggers polymerization of
      the coat protein. Toward an understanding of this process at the molecular level,
      formation of noncovalent complexes and their relative stabilities were analyzed
      by Fourier transform ion cyclotron resonance mass spectrometry using
      nanoelectrospray ionization. Specificity and stability of oligomers formed were
      established to depend on characteristic peptide sequence motifs and were
      confirmed by mass spectrometric competition experiments with control peptides.
      Mutations in the peptide sequence caused decreased interaction and
      destabilization of the noncovalent complexes. The formation and relative
      stabilities of dimeric and tetrameric complexes were assessed to be formed by
      cytoplasmic tails of coatomer receptors. The direct molecular identification
      provided by mass spectrometry correlates well with biochemical results. Thus,
      electrospray ionization mass spectrometry proves to be a powerful tool to
      investigate physiologically relevant peptide complexes.

PMID- 10913255
TI  - Halothane binding to a G protein coupled receptor in retinal membranes by
      photoaffinity labeling.
AB  - General anesthetics have been reported to alter the functions of G protein
      coupled receptor (GPCR) signaling systems. To determine whether these effects
      might be mediated by direct binding interactions with the GPCR or its associated
      G protein, we studied the binding character of halothane on mammalian rhodopsin,
      structurally the best understood GPCR, by using direct photoaffinity labeling
      with [(14)C]halothane. In the bleached bovine rod disk membranes (RDM), opsin and
      membrane lipids were dominantly photolabeled with [(14)C]halothane, but none of
      the three G protein subunits were labeled. In opsin itself, halothane labeling
      was inhibited by unlabeled halothane with an IC(50) of 0.9 mM and a Hill
      coefficient of -0.8. The stoichiometry was 1.1:1.0 (halothane:opsin molar ratio).
      The IC(50) values of isoflurane and 1-chloro-1,2, 2-trifluorocyclobutane were 5.0
      and 15 mM, respectively. Ethanol had no effect on opsin labeling by halothane. A
      nonimmobilizer, 1, 2-dichlorohexafluorocyclobutane, inhibited halothane labeling
      by 50% at 0.05 mM. The present results demonstrate that halothane binds
      specifically and selectively to GPCRs in the RDM. The absence of halothane
      binding to any of the G protein subunits strongly suggests that the functional
      effects of halothane on GPCR signaling systems are mediated by direct
      interactions with receptor proteins.

PMID- 10913256
TI  - Heregulin reverses the oligomerization of HER3.
AB  - We analyzed the propensity of the HER3 receptor and its extracellular domain
      (ECD) to undergo ligand-independent self-association. The HER3-ECD, purified from
      Drosophila S2 cells, binds the EGF-like domain of heregulin (hrg) with a K(d) of
      1.9 nM as measured by surface plasmon resonance (SPR) studies. In a gel shift
      assay, the HER3-ECD self-associates into a uniform, slowly migrating species in a
      concentration-dependent manner, starting at concentrations of <10 nM. In contrast
      to the HER3-ECD, the ECD from the related HER2 receptor does not oligomerize
      under the same conditions. The direct interaction of HER3-ECDs was also
      demonstrated by pull-down assays and SPR measurements under physiological salt
      conditions. This self-association of the HER3-ECD was reversed by the addition of
      hrg but not by EGF. The apparent equilibrium dissociation constant for the HER3
      ECD self-association is 15 nM, based on SPR measurements. In this analysis, hrg
      blocks HER3-ECD self-association, and the addition of hrg during the dissociation
      phase resulted in an accelerated off rate. This finding suggests that hrg can
      bind to and disrupt preexisting HER3-ECD oligomers. Full-length HER3 likewise
      exhibited self-association. Under conditions where co-immunoprecipitation and
      cross-linking of HER2 and HER3 were stimulated by hrg, HER3 self-association and
      cross-linking were disrupted by hrg. The implication is that the self-association
      of HER3-ECD favors the formation of catalytically inactive complexes of the HER3
      receptor. Binding of hrg releases HER3 which may then form signaling-competent
      HER3-HER2 heterodimers.

PMID- 10913257
TI  - The region of antithrombin interacting with full-length heparin chains outside
      the high-affinity pentasaccharide sequence extends to Lys136 but not to Lys139.
AB  - The interaction of a well-defined pentasaccharide sequence of heparin with a
      specific binding site on antithrombin activates the inhibitor through a
      conformational change. This change increases the rate of antithrombin inhibition
      of factor Xa, whereas acceleration of thrombin inhibition requires binding of
      both inhibitor and proteinase to the same heparin chain. An extended heparin
      binding site of antithrombin outside the specific pentasaccharide site has been
      proposed to account for the higher affinity of the inhibitor for full-length
      heparin chains by interacting with saccharides adjacent to the pentasaccharide
      sequence. To resolve conflicting evidence regarding the roles of Lys136 and
      Lys139 in this extended site, we have mutated the two residues to Ala or Gln.
      Mutation of Lys136 decreased the antithrombin affinity for full-length heparin by
      at least 5-fold but minimally altered the affinity for the pentasaccharide. As a
      result, the full-length heparin and pentasaccharide affinities were comparable.
      The reduced affinity for full-length heparin was associated with the loss of one
      ionic interaction and was caused by both a lower overall association rate
      constant and a higher overall dissociation rate constant. In contrast, mutation
      of Lys139 affected neither full-length heparin nor pentasaccharide affinity. The
      rate constants for inhibition of thrombin and factor Xa by the complexes between
      antithrombin and full-length heparin or pentasaccharide were unaffected by both
      mutations, indicating that neither Lys136 nor Lys139 is involved in heparin
      activation of the inhibitor. Together, these results show that Lys136 forms part
      of the extended heparin binding site of antithrombin that participates in the
      binding of full-length heparin chains, whereas Lys139 is located outside this
      site.

PMID- 10913258
TI  - Peptidase specificity characterization of C- and N-terminal catalytic sites of
      angiotensin I-converting enzyme.
AB  - Quenched fluorescence peptides were used to investigate the substrate specificity
      requirements for recombinant wild-type angiotensin I-converting enzyme (ACE) and
      two full-length mutants bearing a single functional active site (N- or C-domain).
      We assayed two series of bradykinin-related peptides flanked by o-aminobenzoic
      acid (Abz) and N-(2,4-dinitrophenyl)ethylenediamine (EDDnp), namely, Abz-GFSPFXQ
      EDDnp and Abz-GFSPFRX-EDDnp (X = natural amino acids), in which the fluorescence
      appeared when Abz/EDDnp are separated by substrate hydrolysis. Abz-GFSPFFQ-EDDnp
      was preferentially hydrolyzed by the C-domain while Abz-GFSPFQQ-EDDnp exhibits
      higher N-domain specificity. Internally quenched fluorescent analogues of N
      acetyl-SDKP-OH were also synthesized and assayed. Abz-SDK(Dnp)P-OH, in which Abz
      and Dnp (2,4-dinitrophenyl) are the fluorescent donor-acceptor pair, was cleaved
      at the D-K(Dnp) bond with high specificity by the ACE N-domain (k(cat)/K(m) = 1.1
      microM(-)(1) s(-)(1)) being practically resistant to hydrolysis by the C-domain.
      The importance of hydroxyl-containing amino acids at the P(2) position for N
      domain specificity was shown by performing the kinetics of hydrolysis of Abz
      TDK(Dnp)P-OH and Abz-YDK(Dnp)P-OH. The peptides Abz-YRK(Dnp)P-OH and Abz
      FRK(Dnp)P-OH which were hydrolyzed by wild-type ACE with K(m) values of 5.1 and
      4.0 microM and k(cat) values of 246 and 210 s(-)(1), respectively, have been
      shown to be excellent substrates for ACE. The differentiation of the catalytic
      specificity of the C- and N-domains of ACE seems to depend on very subtle
      variations on substrate-specific amino acids. The presence of a free C-terminal
      carboxyl group or an aromatic moiety at the same substrate position determines
      specific interactions with the ACE active site which is regulated by chloride and
      seems to distinguish the activities of both domains.

PMID- 10913259
TI  - The O(2) binding pocket of myohemerythrin: role of a conserved leucine.
AB  - A conserved O(2) binding pocket residue in Phascolopsis gouldii myohemerythrin
      (myoHr), namely, L104, was mutated to several other residues, and the effects on
      O(2) association and dissociation rates, O(2) affinity, and autoxidation were
      examined. The L104V, -F, and -Y myoHrs formed stable O(2) adducts whose UV-vis
      and resonance Raman spectra closely matched those of wild-type oxymyoHr. The
      L104V mutation produced only minimal effects on either O(2) association or
      dissociation, whereas the L104F and -Y mutations resulted in 100-300-fold
      decreases in both O(2) association and dissociation rates. These decreases are
      attributed to introduction of steric restrictions into the O(2) binding pocket,
      which are not present in either wild-type or L104V myoHrs. The failure to observe
      increased O(2) association or dissociation rates for L104V indicates that the
      side chain of leucine at position 104 does not sterically "gate" O(2) entry into
      or exit from the binding pocket in the rate-determining step(s). L104V myoHr
      autoxidized approximately 3 times faster than did wild type, whereas L104T
      autoxidized >10(6) times faster than did wild type. The latter large increase is
      attributed to increased side chain polarity, thereby increasing water occupancy
      in the oxymyoHr binding pocket. These results indicate that L104 contributes a
      hydrophobic barrier that restricts water entry into the oxymyoHr binding pocket.
      Thus, a leucine at position 104 in myoHr appears to have the optimal combination
      of size and hydrophobicity to facilitate O(2) binding while simultaneously
      inhibiting autoxidation.

PMID- 10913260
TI  - COUP-TF plays a dual role in the regulation of the ovalbumin gene.
AB  - The ovalbumin (Ov) gene contains a number of regulatory elements that control its
      transcriptional activity and restrict expression to avian oviduct. One major
      regulatory region, the steroid-dependent regulatory element (SDRE), is required
      for induction by estrogen and corticosterone. Another region, the negative
      regulatory element (NRE), downstream of the SDRE, acts primarily to repress gene
      expression. In addition, experiments within indicate that the binding site for
      the COUP transcription factor (COUP-TF) is also required for Ov gene
      transcription. To examine the interactions involving the SDRE, the NRE, and the
      COUP binding sites on Ov gene transcription, mutations in these regions were made
      and transfected into primary oviduct cell cultures. These experiments show that
      without the NRE, the SDRE is sufficient for induction by estrogen and
      corticosterone, irrespective of the COUP site. However, with the NRE intact, the
      COUP site is required for steroid induction, although without the NRE, the COUP
      site attenuates transcriptional activity. More interestingly, overexpression of
      COUP-TF1 with the Ov wild-type reporter construct alleviates the requirement for
      steroid hormones. These results demonstrate that the COUP site is essential and
      has a dual role in Ov gene transcription and that steroid hormones might directly
      or indirectly regulate the activity of COUP-TF1.

PMID- 10913261
TI  - The role of glutamic acid-69 in the activation of Citrobacter freundii tyrosine
      phenol-lyase by monovalent cations.
AB  - Tyrosine phenol-lyase (TPL) from Citrobacter freundii is activated about 30-fold
      by monovalent cations, the most effective being K(+), NH(4)(+), and Rb(+).
      Previous X-ray crystal structure analysis has demonstrated that the monovalent
      cation binding site is located at the interface between subunits, with ligands
      contributed by the carbonyl oxygens of Gly52 and Asn262 from one chain and
      monodentate ligation by one of the epsilon-oxygens of Glu69 from another chain
      [Antson, A. A., Demidkina, T. V., Gollnick, P., Dauter, Z., Von Tersch, R. L.,
      Long, J., Berezhnoy, S. N., Phillips, R. S., Harutyunyan, E. H., and Wilson, K.
      S. (1993) Biochemistry 32, 4195]. We have studied the effect of mutation of Glu69
      to glutamine (E69Q) and aspartate (E69D) to determine the role of Glu69 in the
      activation of TPL. E69Q TPL is activated by K(+), NH(4)(+), and Rb(+), with K(D)
      values similar to wild-type TPL, indicating that the negative charge on Glu69 is
      not necessary for cation binding and activation. In contrast, E69D TPL exhibits
      very low basal activity and only weak activation by monovalent cations, even
      though monovalent cations are capable of binding, indicating that the geometry of
      the monovalent cation binding site is critical for activation. Rapid-scanning
      stopped-flow kinetic studies of wild-type TPL show that the activating effect of
      the cation is seen in an acceleration of rates of quinonoid intermediate
      formation (30-50-fold) and of phenol elimination. Similar rapid-scanning stopped
      flow results were obtained with E69Q TPL; however, E69D TPL shows only a 4-fold
      increase in the rate of quinonoid intermediate formation with K(+). Preincubation
      of TPL with monovalent cations is necessary to observe the rate acceleration in
      stopped flow kinetic experiments, suggesting that the activation of TPL by
      monovalent cations is a slow process. In agreement with this conclusion, a slow
      increase (k < 0.5 s(-)(1)) in fluorescence intensity (lambda(ex) = 420 nm,
      lambda(em) = 505 nm) is observed when wild-type and E69Q TPL are mixed with K(+),
      Rb(+), and NH(4)(+) but not Li(+) or Na(+). E69D TPL shows no change in
      fluorescence under these conditions. High concentrations (>100 mM) of all
      monovalent cations result in inhibition of wild-type TPL. This inhibition is
      probably due to cation binding to the ES complex to form a complex that releases
      pyruvate slowly.

PMID- 10913262
TI  - Enzyme-catalyzed acylation of homoserine: mechanistic characterization of the
      Haemophilus influenzae met2-encoded homoserine transacetylase.
AB  - The first unique step in bacterial and plant methionine biosynthesis involves the
      acylation of the gamma-hydroxyl of homoserine. In Haemophilus influenzae,
      acylation is accomplished via an acetyl-CoA-dependent acetylation catalyzed by
      homoserine transacetylase. The activity of this enzyme regulates flux of
      homoserine into multiple biosynthetic pathways and, therefore, represents a
      critical control point for cell growth and viability. We have cloned homoserine
      transacetylase from H. influenzae and present the first detailed enzymatic study
      of this enzyme. Steady-state kinetic experiments demonstrate that the enzyme
      utilizes a ping-pong kinetic mechanism in which the acetyl group of acetyl-CoA is
      initially transferred to an enzyme nucleophile before subsequent transfer to
      homoserine to form the final product, O-acetylhomoserine. The maximal velocity
      and V/K(homoserine) were independent of pH over the range of values tested, while
      V/K(acetyl)(-)(CoA) was dependent upon the ionization state of a single group
      exhibiting a pK value of 8.6, which was required to be protonated. Solvent
      kinetic isotope effect studies yielded inverse effects of 0.75 on V and 0.74 on
      V/K(CoA) on the reverse reaction and effects of 1.2 on V and 1.7 on
      V/K(homoserine) on the forward reaction. Direct evidence for the formation of an
      acetyl-enzyme intermediate was obtained using rapid-quench labeling studies. On
      the basis of these observations, we propose a chemical mechanism for this
      important member of the acyltransferase family and contrast its mechanism with
      that of homoserine transsuccinylase.

PMID- 10913263
TI  - Crystal structures of fructose 1,6-bisphosphatase: mechanism of catalysis and
      allosteric inhibition revealed in product complexes.
AB  - Crystal structures of metal-product complexes of fructose 1, 6-bisphosphatase
      (FBPase) reveal competition between AMP and divalent cations. In the presence of
      AMP, the Zn(2+)-product and Mg(2+)-product complexes have a divalent cation
      present only at one of three metal binding sites (site 1). The enzyme is in the T
      state conformation with a disordered loop of residues 52-72 (loop 52-72). In the
      absence of AMP, the enzyme crystallizes in the R-state conformation, with loop 52
      72 associated with the active site. In structures without AMP, three metal
      binding sites are occupied by Zn(2+) and two of three metal sites (sites 1 and 2)
      by Mg(2+). Evidently, the association of AMP with FBPase disorders loop 52-72,
      the consequence of which is the release of cations from two of three metal
      binding sites. In the Mg(2+) complexes (but not the Zn(2+) complexes), the 1-OH
      group of fructose 6-phosphate (F6P) coordinates to the metal at site 1 and is
      oriented for a nucleophilic attack on the bound phosphate molecule. A mechanism
      is presented for the forward reaction, in which Asp74 and Glu98 together generate
      a hydroxide anion coordinated to the Mg(2+) at site 2, which then displaces F6P.
      Development of negative charge on the 1-oxygen of F6P is stabilized by its
      coordination to the Mg(2+) at site 1.

PMID- 10913264
TI  - Kinetic and structural characterization of urease active site variants.
AB  - Klebsiella aerogenes urease uses a dinuclear nickel active site to catalyze urea
      hydrolysis at >10(14)-fold the spontaneous rate. To better define the enzyme
      mechanism, we examined the kinetics and structures for a suite of site-directed
      variants involving four residues at the active site: His320, His219, Asp221, and
      Arg336. Compared to wild-type urease, the H320A, H320N, and H320Q variants
      exhibit similar approximately 10(-)(5)-fold deficiencies in rates, modest K(m)
      changes, and disorders in the peptide flap covering their active sites. The pH
      profiles for these mutant enzymes are anomalous with optima near 6 and shoulders
      that extend to pH 9. H219A urease exhibits 10(3)-fold increased K(m) over that of
      native enzyme, whereas the increase is less marked ( approximately 10(2)-fold) in
      the H219N and H219Q variants that retain hydrogen bonding capability. Structures
      for these variants show clearly resolved active site water molecules covered by
      well-ordered peptide flaps. Whereas the D221N variant is only moderately affected
      compared to wild-type enzyme, D221A urease possesses low activity ( approximately
      10(-)(3) that of native enzyme), a small increase in K(m), and a pH 5 optimum.
      The crystal structure for D221A urease is reminiscent of the His320 variants. The
      R336Q enzyme has a approximately 10(-)(4)-fold decreased catalytic rate with near
      normal pH dependence and an unaffected K(m). Phenylglyoxal inactivates the R336Q
      variant at over half the rate observed for native enzyme, demonstrating that
      modification of non-active-site arginines can eliminate activity, perhaps by
      affecting the peptide flap. Our data favor a mechanism in which His219 helps to
      polarize the substrate carbonyl group, a metal-bound terminal hydroxide or
      bridging oxo-dianion attacks urea to form a tetrahedral intermediate, and
      protonation occurs via the general acid His320 with Asp221 and Arg336 orienting
      and influencing the acidity of this residue. Furthermore, we conclude that the
      simple bell-shaped pH dependence of k(cat) and k(cat)/K(m) for the native enzyme
      masks a more complex underlying pH dependence involving at least four pK(a)s.

PMID- 10913265
TI  - Energetic and mechanistic studies of glucoamylase using molecular recognition of
      maltose OH groups coupled with site-directed mutagenesis.
AB  - Molecular recognition using a series of deoxygenated maltose analogues was used
      to determine the substrate transition-state binding energy profiles of 10 single
      residue mutants at the active site of glucoamylase from Aspergillus niger. The
      individual contribution of each substrate hydroxyl group to transition-state
      stabilization with the wild type and each mutant GA was determined from the
      relation Delta(DeltaG()) = -RT ln[(k(cat)/K(M))(x)/(k(cat)/K(M))(y)], where x
      represents either a mutant enzyme or substrate analogue and y the wild-type
      enzyme or parent substrate. The resulting binding energy profiles indicate that
      disrupting an active site hydrogen bond between enzyme and substrate, as
      identified in crystal structures, not only sharply reduces or eliminates the
      energy contributed from that particular hydrogen bond but also perturbs binding
      contributions from other substrate hydroxyl groups. Replacing the active site
      acidic groups, Asp55, Glu180, or Asp309, with the corresponding amides, and the
      neutral Trp178 with the basic Arg, all substantially reduced the binding energy
      contribution of the 4'- and 6'-OH groups of maltose at subsite -1, even though
      both Glu180 and Asp309 are localized at subsite 1. In contrast, the substitution,
      Asp176 --> Asn, located near subsites -1 and 1, did not substantially perturb any
      of the individual hydroxyl group binding energies. Similarly, the substitutions
      Tyr116 --> Ala, Ser119 --> Tyr, or Trp120 --> Phe also did not substantially
      alter the energy profiles even though Trp120 has a critical role in directing
      conformational changes necessary for activity. Since the mutations at Trp120 and
      Asp176 reduced k(cat) values by 50- and 12-fold, respectively, a large effect on
      k(cat) is not necessarily accompanied by changes in hydroxyl group binding energy
      contributions. Two substitutions, Asn182 --> Ala and Tyr306 --> Phe, had
      significant though small effects on interactions with 3- and 4'-OH, respectively.
      Binding interactions between the enzyme and the glucosyl group in subsite -1,
      particularly with the 4'- and 6'-OH groups, play an important role in substrate
      binding, while subsite 1 interactions may play a more important role in product
      release.

PMID- 10913266
TI  - Tight binding inhibitors of scytalone dehydratase: effects of site-directed
      mutations.
AB  - We explore the use of site-directed mutations of scytalone dehydratase to study
      inhibitor binding interactions. The enzyme is the physiological target of new
      fungicides and the subject of inhibitor design and optimization. X-ray structures
      show that potent inhibitors (K(i)'s approximately 10(-)(11) M) interact mostly
      with 11 amino acid side chains and, in some cases, with a single backbone amide.
      Fifteen site-directed mutants of the 11 enzyme residues were prepared to disrupt
      enzyme-inhibitor interactions, and inhibition constants for 13 inhibitors were
      determined to assess changes in binding potencies. The results indicate that two
      of the six hydrogen bonds (always present in X-ray structures of native enzyme
      inhibitor complexes) are not important for inhibitor binding. The other four
      hydrogen bonds are important for inhibitor binding, and the strength of the
      individual bonds is inhibitor-dependent. Inhibitor atoms remote from the hydrogen
      bonds influence their strength, presumably by effecting small changes in
      inhibitor orientation. Several hydrophobic amino acid residues are important
      recognition elements for lipophilic inhibitor functionalities, which is fully
      consistent with X-ray structures determined from crystals of enzyme-inhibitor
      complexes grown at neutral pH but not with those determined from crystals grown
      under acidic conditions. This study of mutant enzymes complements insights from X
      ray structures and structure-activity relationships of the wild-type enzyme for
      refining views of inhibitor recognition.

PMID- 10913267
TI  - GDP-mannose mannosyl hydrolase catalyzes nucleophilic substitution at carbon,
      unlike all other Nudix hydrolases.
AB  - GDP-mannose mannosyl hydrolase (GDPMH) from Escherichia coli is a 36. 8 kDa
      homodimer which, in the presence of Mg(2+), catalyzes the hydrolysis of GDP-alpha
      D-mannose or GDP-alpha-D-glucose to yield sugar and GDP. On the basis of its
      amino acid sequence, GDPMH is a member of the Nudix family of enzymes which
      catalyze the hydrolysis of nucleoside diphosphate derivatives by nucleophilic
      substitution at phosphorus. However, GDPMH has a sequence rearrangement (RE to
      ER) in the conserved Nudix motif and is missing a Glu residue characteristic of
      the Nudix signature sequence. By (1)H NMR, the initial hydrolysis product of GDP
      alpha-D-glucose is beta-D-glucose, indicating nucleophilic substitution with
      inversion at C1' of glucose. Substitution at carbon was confirmed by two
      dimensional (1)H-(13)C HSQC spectra of the products of hydrolysis in 48.4% (18)O
      labeled water which showed an additional C1' resonance of beta-D-glucose with a
      typical upfield (18)O isotope shift of 18 ppb and an intensity of 47.6% of the
      total signal. No (18)O isotope-shifted resonances (<4%) were found in the (31)P
      NMR spectrum of the GDP product. Thus, unlike all other Nudix enzymes studied so
      far, GDPMH catalyzes nucleophilic substitution at carbon rather than at
      phosphorus. A small solvent kinetic deuterium isotope effect on k(cat) of 1.76 +/
      0.25, independent of pH over the range of 6.0-9.3, suggests that the
      deprotonation of water may be part of the rate-limiting step.

PMID- 10913268
TI  - Three-dimensional structure and subunit topology of the V(1) ATPase from Manduca
      sexta midgut.
AB  - The three-dimensional structure of the Manduca sexta midgut V(1) ATPase has been
      determined at 3.2 nm resolution from electron micrographs of negatively stained
      specimens. The V(1) complex has a barrel-like structure 11 nm in height and 13.5
      nm in diameter. It is hexagonal in the top view, whereas in the side view, the
      six large subunits A and B are interdigitated for most of their length (9 nm).
      The topology and importance of the individual subunits of the V(1) complex have
      been explored by protease digestion, resistance to chaotropic agents, MALDI-TOF
      mass spectrometry, and CuCl(2)-induced disulfide formation. Treatment of V(1)
      with trypsin or chaotropic iodide resulted in a rapid cleavage or release of
      subunit D from the enzyme, indicating that this subunit is exposed in the
      complex. Trypsin cleavage of V(1) decreased the ATPase activity with a time
      course that was in line with the cleavage of subunits B, C, G, and F. When
      CuCl(2) was added to V(1) in the presence of CaADP, the cross-linked products A-E
      F and B-H were generated. In experiments where CuCl(2) was added after
      preincubation of CaATP, the cross-linked products E-F and E-G were formed. These
      changes in cross-linking of subunit E to near-neighbor subunits support the
      hypothesis that these are nucleotide-dependent conformational changes of the E
      subunit.

PMID- 10913269
TI  - The distal heme center in Bacillus subtilis succinate:quinone reductase is
      crucial for electron transfer to menaquinone.
AB  - Succinate:quinone reductases are membrane-bound enzymes that catalyze electron
      transfer from succinate to quinone. Some enzymes in vivo reduce ubiquinone
      (exergonic reaction) whereas others reduce menaquinone (endergonic reaction). The
      succinate:menaquinone reductases all contain two heme groups in the membrane
      anchor of the enzyme: a proximal heme (heme b(P)) located close to the negative
      side of the membrane and a distal heme (heme b(D)) located close to the positive
      side of the membrane. Heme b(D) is a distinctive feature of the
      succinate:menaquinone reductases, but the role of this heme in electron transfer
      to quinone has not previously been analyzed. His28 and His113 are the axial
      ligands to heme b(D) in Bacillus subtilis succinate:menaquinone reductase. We
      have individually replaced these His residues with Leu and Met, respectively,
      resulting in assembled membrane-bound enzymes. The H28L mutant enzyme lacks
      succinate:quinone reductase activity probably due to a defective quinone binding
      site. The H113M mutant enzyme contains heme b(D) with raised midpoint potential
      and is impaired in electron transfer to menaquinone. Our combined experimental
      data show that the heme b(D) center, into which we include a quinone binding
      site, is crucial for succinate:menaquinone reductase activity. The results
      support a model in which menaquinone is reduced on the positive side of the
      membrane and the transmembrane electrochemical potential provides driving force
      for electron transfer from succinate via heme b(P) and heme b(D) to menaquinone.

PMID- 10913271
TI  - Colicin pore-forming domains bind to Escherichia coli trimeric porins.
AB  - Colicin N kills sensitive Escherichia coli cells by first binding to its trimeric
      receptor (OmpF) via its receptor binding domain. It then uses OmpF to translocate
      across the outer membrane and in the process it also needs domains II and III of
      the protein TolA. Recent studies have demonstrated sodium dodecyl sulfate- (SDS)
      dependent complex formation between trimeric porins and TolA-II. Here we
      demonstrate that colicin N forms similar complexes with the same trimeric porins
      and that this association is unexpectedly solely dependent upon the pore-forming
      domain (P-domain). No binding was seen with the monomeric porin OmpA. In mixtures
      of P-domain and TolA with OmpF porin, only binary and no ternary complexes were
      observed, suggesting that binding of these proteins to the porin is mutually
      exclusive. Pull-down assays in solution show that porin-P-domain complexes also
      form in the presence of outer membrane lipopolysaccharide. This indicates that an
      additional colicin-porin interaction may occur within the outer membrane, one
      that involves the colicin pore domain rather than the receptor-binding domain.
      This may help to explain the role of porins and TolA-II in the later stages of
      colicin translocation.

PMID- 10913270
TI  - Evidence for two spectroscopically different dimers of light-harvesting complex I
      from green plants.
AB  - A preparation consisting of isolated dimeric peripheral antenna complexes from
      green plant photosystem I (light-harvesting complex I or LHCI) has been
      characterized by means of (polarized) steady-state absorption and fluorescence
      spectroscopy at low temperatures. We show that this preparation can be described
      reasonably well by a mixture of two types of dimers. In the first dimer about 10%
      of all Q(y)() absorption of the chlorophylls arises from two chlorophylls with
      absorption and emission maxima at about 711 and 733 nm, respectively, whereas in
      the second about 10% of the absorption arises from two chlorophylls with
      absorption and emission maxima at about 693 and 702 nm, respectively. The
      remaining chlorophylls show spectroscopic properties comparable to those of the
      related peripheral antenna complexes of photosystem II. We attribute the first
      dimer to a heterodimer of the Lhca1 and Lhca4 proteins and the second to a hetero
      or homodimer of the Lhca2 and/or Lhca3 proteins. We suggest that the
      chlorophylls responsible for the 733 nm emission (F-730) and 702 nm emission (F
      702) are excitonically coupled dimers and that F-730 originates from one of the
      strongest coupled pair of chlorophylls observed in nature.

PMID- 10913272
TI  - Interaction of the gonococcal porin P.IB with G- and F-actin.
AB  - The invasion of epithelial cells by N. gonorrheae is accompanied by formation of
      a halo of actin filaments around the enveloped bacterium. The transfer of the
      bacterial major outer membrane protein, porin, to the host cell membrane during
      invasion makes it a candidate for a facilitator for the formation of this halo.
      Western analysis shows here that gonococcal porin P.IB associates with the actin
      cytoskeleton in infected cells. Using the pyrene-labeled Mg forms of yeast and
      muscle actins, we demonstrate that under low ionic strength conditions, P.IB
      causes formation of filamentous actin assemblies, although they, unlike F-actin,
      cannot be internally cross-linked with N,N'-4-phenylenedimaleimide (PDM). In F
      buffer, low porin concentrations appear to accelerate actin polymerization.
      Higher P.IB concentrations lead to the formation of highly decorated fragmented F
      actin-like filaments in which the actin can be cross-linked by PDM. Co-assembly
      of P.IB with a pyrene-labeled mutant actin, S(265)C, prevents formation of a
      pyrene excimer present with labeled S(265)C F-actin alone. Addition of low
      concentrations of porin to preformed F-actin results in sparsely decorated F
      actin. Higher P.IB concentrations extensively decorate the filaments, thereby
      altering their morphology to a state like that observed when the components are
      copolymerized. With preformed labeled S(265)C F-actin, P.IB quenches the pyrene
      excimer. This decrease is prevented by the F-actin stabilizers phalloidin and to
      a lesser extent beryllium fluoride. P.IB's association with the actin
      cytoskeleton and its ability to interact with and remodel actin filaments support
      a direct role for porin in altering the host cell cytoskeleton during invasion.

PMID- 10913273
TI  - Interactions of the novel antimicrobial peptide buforin 2 with lipid bilayers:
      proline as a translocation promoting factor.
AB  - Buforin 2 is an antimicrobial peptide discovered in the stomach tissue of the
      Asian toad Bufo bufo gargarizans. The 21-residue peptide with +6 net charge shows
      antimicrobial activity an order of magnitude higher than that of magainin 2, a
      membrane-permeabilizing antimicrobial peptide from Xenopus laevis [Park, C. B.,
      Kim, M. S., and Kim, S. C. (1996) Biochem. Biophys. Res. Commun. 218, 408-413].
      In this study, we investigated the interactions of buforin 2 with phospholipid
      bilayers in comparison with magainin 2 to obtain insight into the mechanism of
      action of buforin 2. Equipotent Trp-substituted peptides were used to
      fluorometrically monitor peptide-lipid interactions. Circular dichroism
      measurements showed that buforin 2 selectively bound to liposomes composed of
      acidic phospholipids, assuming a secondary structure similar to that in
      trifluoroethanol/water, which is an amphipathic helix distorted around Pro(11)
      with a flexible N-terminal region [Yi, G. S., Park, C. B., Kim, S. C., and
      Cheong, C. (1996) FEBS Lett. 398, 87-90]. Magainin 2 induced the leakage of a
      fluorescent dye entrapped within lipid vesicles coupled to lipid flip-flop. These
      results have been interpreted as the formation of a peptide-lipid supramolecular
      complex pore [Matsuzaki, K. (1998) Biochim. Biophys. Acta 1376, 391-400]. Buforin
      2 exhibited much weaker membrane permeabilization activity despite its higher
      antimicrobial activity. In contrast, buforin 2 was more efficiently translocated
      across lipid bilayers than magainin 2. These results suggested that the ultimate
      target of buforin 2 is not the membrane but intracellular components.
      Furthermore, buforin 2 induced no lipid flip-flop, indicating that the mechanism
      of translocation of buforin 2 is different from that of magainin 2. The role of
      Pro was investigated by use of a P11A derivative of buforin 2. The derivation
      caused a change to magainin 2-like secondary structure and membrane behavior.
      Pro(11) was found to be a very important structural factor for the unique
      properties of buforin 2.

PMID- 10913274
TI  - Role of amino acid residues at turns in the conformational stability and folding
      of human lysozyme.
AB  - To clarify the role of amino acid residues at turns in the conformational
      stability and folding of a globular protein, six mutant human lysozymes deleted
      or substituted at turn structures were investigated by calorimetry, GuHCl
      denaturation experiments, and X-ray crystal analysis. The thermodynamic
      properties of the mutant and wild-type human lysozymes were compared and
      discussed on the basis of their three-dimensional structures. For the deletion
      mutants, Delta47-48 and Delta101, the deleted residues are in turns on the
      surface and are absent in human alpha-lactalbumin, which is homologous to human
      lysozyme in amino acid sequence and tertiary structure. The stability of both
      mutants would be expected to increase due to a decrease in conformational entropy
      in the denatured state; however, both proteins were destabilized. The
      destabilizations were mainly caused by the disappearance of intramolecular
      hydrogen bonds. Each part deleted was recovered by the turn region like the alpha
      lactalbumin structure, but there were differences in the main-chain conformation
      of the turn between each deletion mutant and alpha-lactalbumin even if the loop
      length was the same. For the point mutants, R50G, Q58G, H78G, and G37Q, the main
      chain conformations of these substitution residues located in turns adopt a left
      handed helical region in the wild-type structure. It is thought that the left
      handed non-Gly residue has unfavorable conformational energy compared to the left
      handed Gly residue. Q58G was stabilized, but the others had little effect on the
      stability. The structural analysis revealed that the turns could rearrange the
      main-chain conformation to accommodate the left-handed non-Gly residues. The
      present results indicate that turn structures are able to change their main-chain
      conformations, depending upon the side-chain features of amino acid residues on
      the turns. Furthermore, stopped-flow GuHCl denaturation experiments on the six
      mutants were performed. The effects of mutations on unfolding-refolding kinetics
      were significantly different among the mutant proteins. The
      deletion/substitutions in turns located in the alpha-domain of human lysozyme
      affected the refolding rate, indicating the contribution of turn structures to
      the folding of a globular protein.

PMID- 10913275
TI  - Site-directed mutagenesis and biochemical analysis of the endogenous ligands in
      the ferrous active site of clavaminate synthase. The His-3 variant of the 2-His-1
      carboxylate model.
AB  - The facial 2-His-1-carboxylate (Asp/Glu) motif has emerged as the structural
      paradigm for metal binding in the alpha-ketoglutarate (alpha-KG)-dependent
      nonheme iron oxygenases. Clavaminate synthase (CS2) is an unusual member of this
      enzyme family that mediates three different, nonsequential reactions during the
      biosynthesis of the beta-lactamase inhibitor clavulanic acid. In this study,
      covalent modification of CS2 by the affinity label N-bromoacetyl-L-arginine near
      His297, which is within the HRV signature of a His-2 motif, suggested this
      histidine could play a role in metal coordination. However, site-specific
      mutagenesis of eight His residues to Gln identified His145 and His280, but not
      His297, as involved in iron binding. Weak homology of His145 and its flanking
      sequence and the presence of Glu147 fitting the canonical acidic residue of the
      His-Xaa-Asp/Glu signature are consistent with His145 being a coordinating ligand
      (His-1). His280 and its flanking sequence, which give poor alignments to most
      other members of this enzyme family, are similar among a subset of these enzymes
      and notably to CarC, an apparent oxygenase involved in carbapenem biosynthesis.
      The separation of His145 and His280 is more than twice that seen in the current 2
      His-1-carboxylate model and may define an alternative iron binding motif, which
      we propose as His-3. These ligand assignments, based on kinetic measurements of
      both oxidative cyclization/desaturation and hydroxylation assays, establish that
      no histidine ligand switching occurs during the catalytic cycle. These results
      are confirmed in a recent X-ray crystal structure of CS1, a highly similar
      isozyme of CS2 (81% identical). Tyr299, Tyr300 in CS2 modified by N-bromoacetyl-L
      arginine, is hydrogen bonded to Glu146 (Glu147 in CS2) in this structure and well
      positioned for reaction with the affinity label.

PMID- 10913276
TI  - Direct interaction of SOS1 Ras exchange protein with the SH3 domain of
      phospholipase C-gamma1.
AB  - A recent report that microinjection of the SH3 domain of PLC-gamma1 could induce
      DNA synthesis raised the functional importance of the SH3 domain of PLC-gamma1 in
      mitogenic signaling. In this report, we provide evidence that SOS1, a p21Ras
      specific guanine nucleotide exchange factor, directly binds to the SH3 domain of
      PLC-gamma1, and that the SH3 domain of PLC-gamma1 is involved in SOS1-mediated
      p21Ras activation. SOS1 was coprecipitated with the GST-fused SH3 domain of PLC
      gamma1 in vitro. The interaction between SOS1 and the PLC-gamma1 SH3 domain is
      mediated by direct physical interaction. The carboxyl-terminal proline-rich
      domain of SOS1 is involved in the interaction with the PLC-gamma1 SH3 domain.
      Moreover, PLC-gamma1 could be co-immunoprecipitated with SOS1 antibody in cell
      lysates. From transient expression studies, we could demonstrate that the SH3
      domain of PLC-gamma1 is necessary for the association with SOS1 in vivo.
      Intriguingly, overexpression of the SH3 domain of PLC-gamma1, lipase-inactive PLC
      gamma1, or wild-type PLC-gamma1 elevated p21Ras activity and ERK activity when
      compared with vector transfected cells. The PLC-gamma1 mutant lacking the SH3
      domain could not activate p21Ras. p21Ras activities in cell lines overexpressing
      either PLC-gamma1 or the SH2-SH2-SH3 domain of PLC-gamma1 were elevated about 2
      fold compared to vector transfected cells. This study is the first to demonstrate
      that the PLC-gamma1 SH3 domain enhances p21Ras activity, and that the SH3 domain
      of PLC-gamma1 may be involved in the SOS1-mediated signaling pathway.

PMID- 10913278
TI  - Effects of cholesterol and enantiomeric cholesterol on P-glycoprotein
      localization and function in low-density membrane domains

PMID- 10913277
TI  - Triplex formation by psoralen-conjugated chimeric oligonucleoside
      methylphosphonates.
AB  - Interactions between nuclease-resistant, 5'-psoralen-conjugated, chimeric
      methylphosphonate oligodeoxyribo- or oligo-2'-O-methylribo-triplex-forming
      oligomers (TFOs) and a purine tract found in the envelope gene of HIV proviral
      DNA (env-DNA) were investigated by gel mobility shift assays or by photo-cross
      linking experiments. These chimeric TFOs contain mixtures of methylphosphonate
      and phosphodiester internucleotide bonds. A pyrimidine chimeric TFO composed of
      thymidine and 5-methyl-2'-deoxycytidine (C), d-PS-TpCpTpCpTpCpTpTpTpTpTpTpCpTpC
      (1mp) where PS is trimethylpsoralen and p is methylphosphonate, forms a stable
      triplex with env-DNA whose dissociation constant is 1. 3 microM at 22 degrees C
      and pH 7.0. The dissociation constant of chimeric TFO 2mp, d-PS
      UpCpTpCpTpCpTpUpTpUpTpUpCpTpC, decreased to 400 nM when four of the thymidines in
      1mp were replaced by 5-propynyl-2'-deoxyuridines (U), a result consistent with
      the increased stacking interactions and hydrophobic nature of 5-propynyl-U. An
      even greater decrease, 470 -50 nM, was observed for the all-phosphodiester
      versions of 1mp and 2mp. The differences in behavior of the chimeric versus the
      all-phosphodiester oligomers may be related to differences in the conformations
      between the propynyl-U-substituted versus the nonsubstituted TFOs. Thus, in the
      chimeric oligomer, the stabilizing effect of the propynyl-U's may be offset by
      the reduced ability of the methylphosphonate backbone to assume an A-type
      conformation, a conformation that appears to be preferred by propynyl-U
      containing TFOs. A chimeric oligo-2'-O-methylribopyrimidine with the same
      sequence as 1mp also formed a stable triplex, K(d) = 1.4 microM, with env-DNA. In
      contrast to the behavior of the pyrimidine TFOs, antiparallel A/G oligomers and
      parallel or antiparallel T/G oligomers did not form triplexes with env-DNA, even
      at oligomer concentrations of 10 microM. This lack of binding may be a
      consequence of the low G content (33%) of the triplex binding site. Irradiation
      of triplexes formed between the pyrimidine TFOs and env-DNA resulted in formation
      of photoadducts with either the upper-strand C or the lower-strand T at the 5'
      CpA-3' duplex/triplex junction. No interstrand cross-links were observed. The
      presence of a 5-propynyl-U at the 5'-end of the oligomer caused a reduction in
      the amount of upper-strand photoadduct but had no effect on photoadduct formation
      with the lower strand, suggesting that increased stacking interactions caused by
      the presence of the 5-propynyl-U change the orientation of psoralen with respect
      to the upper-strand C. The ability of chimeric methylphosphonate TFOs to bind to
      DNA, combined with their resistance to degradation by serum 3'-exonucleases,
      suggests that they may have utility in biological experiments.

PMID- 10913279
TI  - Ligand--protein interactions in the glutamate receptor.
AB  - Fourier transform infrared spectroscopy was used to investigate ligand-protein
      interactions in the ligand-binding domain of the GluR4 glutamate receptor
      subunit. Glutamate binding induces more extensive secondary structural changes in
      the ligand-binding domain than does kainate binding. Glutamate also alters the
      hydrogen bonding strength of the single free cysteine side chain in the domain,
      while kainate does not. On the other hand, the interaction of a binding site
      arginine residue with kainate appears to be stronger than that with glutamate.
      These results identify chemical and structural differences that may explain the
      different functional characteristics of the two agonists acting on ionotropic
      glutamate receptors. In doing so, they complement and extend recent
      crystallographic structures of the ligand-binding domain.

PMID- 10913280
TI  - L-685,458, an aspartyl protease transition state mimic, is a potent inhibitor of
      amyloid beta-protein precursor gamma-secretase activity.
AB  - Progressive cerebral amyloid beta-protein (A beta) deposition is believed to play
      a central role in the pathogenesis of Alzheimer's disease (AD). Elevated levels
      of A beta(42) peptide formation have been linked to early-onset familial AD
      causing gene mutations in the amyloid beta-protein precursor (A beta PP) and the
      presenilins. Sequential cleavage of A beta PP by the beta- and gamma-secretases
      generates the N- and C-termini of the A beta peptide, making both the beta- and
      gamma-secretase enzymes potential therapeutic targets for AD. The identity of the
      A beta PP gamma-secretase and the mechanism by which the C-termini of A beta are
      formed remain uncertain, although it has been suggested that the presenilins
      themselves are novel intramembrane-cleaving gamma-secretases of the aspartyl
      protease class [Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S.,
      Kimberly, W. T., and Selkoe, D. J. (1999) Nature 398, 513-517]. In this study we
      report the identification of L-685,458 as a structurally novel inhibitor of A
      beta PP gamma-secretase activity, with a similar potency for inhibition of A
      beta(42) and A beta(40) peptides. This compound contains an hydroxyethylene
      dipeptide isostere which suggests that it could function as a transition state
      analogue mimic of an aspartyl protease. The preferred stereochemistry of the
      hydroxyethylene dipeptide isostere was found to be the opposite to that required
      for inhibition of the HIV-1 aspartyl protease, a factor which may contribute to
      the observed specificity of this compound. Specific and potent inhibitors of A
      beta PP gamma-secretase activity such as L-685,458 will enable important advances
      toward the identification and elucidation of the mechanism of action of this
      enigmatic protease.

PMID- 10913281
TI  - Comparison of the structural stability of two homologous toxins isolated from the
      Taiwan cobra (Naja naja atra) venom.
AB  - Cardiotoxin analogue III (CTX III) and cobrotoxin (CBTX) isolated from the Taiwan
      cobra venom (Naja naja atra) are structurally homologous, small molecular weight,
      all-beta-sheet proteins, cross-linked by four disulfide bonds at identical
      positions. The conformational stabilities of these toxins are compared based on
      temperature-dependent chemical shifts and amide proton exchange kinetics using
      two-dimensional NMR spectroscopy. The structure of CTX III is found to be
      significantly more stable than that of CBTX. In both the toxins, beta-strand III
      appears to constitute the stability core. In CTX III, the stability of the triple
      stranded beta-sheet domain is observed to be markedly higher than the double
      stranded beta-sheet segment. In contrast, in CBTX, both structural domains
      (double- and triple-stranded beta-sheet domains) appear to contribute equally to
      the stability of the protein. Estimation of the free energy of exchange (Delta
      G(ex)) of residues in CBTX and CTX III reveals that the enhanced stability of the
      structure of CTX III stems from the strong interactions among the beta-strands
      constituting the triple-stranded beta-sheet domain and also the molecular forces
      bridging the residues at the N- and C-terminal ends of the molecule.

PMID- 10913282
TI  - Onconase: an unusually stable protein.
AB  - Several members of the RNase A superfamily are endowed with antitumor activity,
      showing selective cytotoxicity toward tumor cell lines. One of these is onconase,
      the smallest member of the superfamily, which at present is undergoing phase-III
      clinical trials as an antitumor drug. Our investigation focused on other
      interesting features of the enzyme, such as its unusually high denaturation
      temperature, its low catalytic activity, and its renal toxicity as a drug. We
      used differential scanning calorimetry, circular dichroism, fluorescence
      measurements, and limited proteolysis to investigate the molecular determinants
      of the stability of onconase and of a mutant, (M23L)-ONC, which is catalytically
      more active than the wild-type enzyme, and fully active as an antitumor agent.
      The determination of the main thermodynamic parameters of the protein led to the
      conclusion that onconase is an unusually stable protein. This was confirmed by
      its resistance to proteolysis. On the basis of this analysis and on a comparative
      analysis of the (M23L)-ONC variant of the protein, which is less stable and more
      sensitive to proteolysis, a model was constructed in line with available data.
      This model supports a satisfactory hypothesis of the molecular basis of onconase
      stability and low-catalytic activity.

PMID- 10913284
TI  - Sticky-end assembly of a designed peptide fiber provides insight into protein
      fibrillogenesis.
AB  - Coiled-coil motifs provide simple systems for studying molecular self-assembly.
      We designed two 28-residue peptides to assemble into an extended coiled-coil
      fiber. Complementary interactions in the core and flanking ion-pairs were used to
      direct staggered heterodimers. These had "sticky-ends" to promote the formation
      of long fibers. For comparison, we also synthesized a permuted version of one
      peptide to associate with the other peptide and form canonical heterodimers with
      "blunt-ends" that could not associate longitudinally. The assembly of both pairs
      was monitored in solution using circular dichroism spectroscopy. In each case,
      mixing the peptides led to increased and concentration-dependent circular
      dichroism signals at 222 nm, consistent with the desired alpha-helical
      structures. For the designed fiber-producing peptide mixture, we also observed a
      linear dichroism effect during flow orientation, indicative of the presence of
      long fibrous structures. X-ray fiber diffraction of partially aligned samples
      gave patterns indicative of coiled-coil structure. Furthermore, we used electron
      microscopy to visualize fiber formation directly. Interestingly, the fibers
      observed were at least several hundred micrometers long and 20 times thicker than
      expected for the dimeric coiled-coil design. This additional thickness implied
      lateral association of the designed structures. We propose that complementary
      features present in repeating structures of the type we describe promote lateral
      assembly, and that a similar mechanism may underlie fibrillogenesis in certain
      natural systems.

PMID- 10913283
TI  - Determination of the structure of Escherichia coli glyoxalase I suggests a
      structural basis for differential metal activation.
AB  - The metalloenzyme glyoxalase I (GlxI) converts the nonenzymatically produced
      hemimercaptal of cytotoxic methylglyoxal and glutathione to nontoxic S-D
      lactoylglutathione. Human GlxI, for which the structure is known, is active in
      the presence of Zn(2+). Unexpectedly, the Escherichia coli enzyme is inactive in
      the presence of Zn(2+) and is maximally active with Ni(2+). To understand this
      difference in metal activation and also to obtain a representative of the
      bacterial enzymes, the structure of E. coli Ni(2+)-GlxI has been determined.
      Structures have also been determined for the apo enzyme as well as complexes with
      Co(2+), Cd(2+), and Zn(2+). It is found that each of the protein-metal complexes
      that is catalytically active has octahedral geometry. This includes the complexes
      of the E. coli enzyme with Ni(2+), Co(2+), and Cd(2+), as well as the structures
      reported for the human Zn(2+) enzyme. Conversely, the complex of the E. coli
      enzyme with Zn(2+) has trigonal bipyramidal coordination and is inactive. This
      mode of coordination includes four protein ligands plus a single water molecule.
      In contrast, the coordination in the active forms of the enzyme includes two
      water molecules bound to the metal ion, suggesting that this may be a key feature
      of the catalytic mechanism. A comparison of the human and E. coli enzymes
      suggests that there are differences between the active sites that might be
      exploited for therapeutic use.

PMID- 10913285
TI  - Partially unfolded states of beta(2)-microglobulin and amyloid formation in
      vitro.
AB  - Dialysis-related amyloidosis (DRA) involves the aggregation of beta(2)
      microglobulin (beta(2)m) into amyloid fibrils. Using Congo red and thioflavin-T
      binding, electron microscopy, and X-ray fiber diffraction, we have determined
      conditions under which recombinant monomeric beta(2)m spontaneously associates to
      form fibrils in vitro. Fibrillogenesis is critically dependent on the pH and the
      ionic strength of the solution, with low pH and high ionic strength favoring
      fibril formation. The morphology of the fibrils formed varies with the growth
      conditions. At pH 4 in 0.4 M NaCl the fibrils are approximately 10 nm wide,
      relatively short (50-200 nm), and curvilinear. By contrast, at pH 1.6 the fibrils
      formed have the same width and morphology as those formed at pH 4 but extend to
      more than 600 nm in length. The dependence of fibril growth on ionic strength has
      allowed the conformational properties of monomeric beta(2)m to be determined
      under conditions where fibril growth is impaired. Circular dichroism studies show
      that titration of one or more residues with a pK(a) of 4.7 destabilizes native
      beta(2)m and generates a partially unfolded species. On average, these molecules
      retain significant secondary structure and have residual, non-native tertiary
      structure. They also bind the hydrophobic dye 1-anilinonaphthalene-8-sulfonic
      acid (ANS), show line broadening in one-dimensional (1)H NMR spectra, and are
      weakly protected from hydrogen exchange. Further acidification destabilizes this
      species, generating a second, more highly denatured state that is less
      fibrillogenic. These data are consistent with a model for beta(2)m
      fibrillogenesis in vitro involving the association of partially unfolded
      molecules into ordered fibrillar assemblies.

PMID- 10913286
TI  - Changes in dynamical behavior of the retinoid X receptor DNA-binding domain upon
      binding to a 14 base-pair DNA half site.
AB  - The retinoid X receptor (RXR) is a prominent member of the nuclear receptor
      family of ligand-inducible transcription factors. Many proteins of this family
      exert their function as heterodimers with RXR as a common upstream partner.
      Studies of the DNA-binding domains of several nuclear receptors reveal
      differences in structure and dynamics, both between the different proteins and
      between the free- and DNA-bound receptor DBDs. We investigated the differences in
      dynamics between RXR free in solution and in complex with a 14 base-pair
      oligonucleotide, using (1)H and (15)N relaxation studies. Nano- to picosecond
      dynamics were probed on (15)N, employing Lipari-Szabo analysis with an axially
      symmetric tumbling model to estimate the exchange contributions to the transverse
      relaxation rates. Furthermore, milli- to microsecond dynamics were estimated
      qualitatively for (1)H and (15)N, using CPMG-HSQC and CPMG-T(2) measurements with
      differential pulse spacing. RXR shows hardly any nano- to picosecond time-scale
      internal motion. Upon DNA binding, the order parameters show a tiny increase.
      Dynamics in the milli- to microsecond time scale is more prevalent. It is
      localized in the first and second zinc fingers of the free RXR. Upon DNA-binding,
      exchange associated with specific/aspecific DNA-binding of RXR is observed
      throughout the sequence, whereas conformational flexibility of the D-box and the
      second zinc finger of RXR is greatly reduced. Since this DNA-binding induced
      folding transition occurs remote from the DNA in a region which is involved in
      protein-protein interactions, it may very well be related to the cooperativity of
      dimeric DNA binding.

PMID- 10913287
TI  - Detailed characterization of the cooperative mechanism of Ca(2+) binding and
      catalytic activation in the Ca(2+) transport (SERCA) ATPase.
AB  - Expression of heterologous SERCA1a ATPase in Cos-1 cells was optimized to yield
      levels that account for 10-15% of the microsomal protein, as revealed by protein
      staining on electrophoretic gels. This high level of expression significantly
      improved our characterization of mutants, including direct measurements of Ca(2+)
      binding by the ATPase in the absence of ATP, and measurements of various enzyme
      functions in the presence of ATP or P(i). Mutational analysis distinguished two
      groups of amino acids within the transmembrane domain: The first group includes
      Glu771 (M5), Thr799 (M6), Asp800 (M6), and Glu908 (M8), whose individual
      mutations totally inhibit binding of the two Ca(2+) required for activation of
      one ATPase molecule. The second group includes Glu309 (M4) and Asn796 (M6), whose
      individual or combined mutations inhibit binding of only one and the same Ca(2+).
      The effects of mutations of these amino acids were interpreted in the light of
      recent information on the ATPase high-resolution structure, explaining the
      mechanism of Ca(2+) binding and catalytic activation in terms of two cooperative
      sites. The Glu771, Thr799, and Asp800 side chains contribute prominently to site
      1, together with less prominent contributions by Asn768 and Glu908. The Glu309,
      Asn796, and Asp800 side chains, as well as the Ala305 (and possibly Val304 and
      Ile307) carbonyl oxygen, contribute to site 2. Sequential binding begins with
      Ca(2+) occupancy of site 1, followed by transition to a conformation (E')
      sensitive to Ca(2+) inhibition of enzyme phosphorylation by P(i), but still
      unable to utilize ATP. The E' conformation accepts the second Ca(2+) on site 2,
      producing then a conformation (E' ') which is able to utilize ATP. Mutations of
      residues (Asp813 and Asp818) in the M6/M7 loop reduce Ca(2+) affinity and
      catalytic turnover, suggesting a strong influence of this loop on the correct
      positioning of the M6 helix. Mutation of Asp351 (at the catalytic site within the
      cytosolic domain) produces total inhibition of ATP utilization and enzyme
      phosphorylation by P(i), without a significant effect on Ca(2+) binding.

PMID- 10913288
TI  - Probing the S1/S1' substrate binding pocket geometry of HIV-1 protease with
      modified aspartic acid analogues.
AB  - Aspartates 25 and 125, the active site residues of HIV-1 protease, participate
      functionally in proteolysis by what is believed to be a general acid-general base
      mechanism. However, the structural role that these residues may play in the
      formation and maintenance of the neighboring S1/S1' substrate binding pockets
      remains largely unstudied. Because the active site aspartic acids are essential
      for catalysis, alteration of these residues to any other naturally occurring
      amino acid by conventional site-directed mutagenesis renders the protease
      inactive, and hence impossible to characterize functionally. To investigate
      whether Asp-25 and Asp-125 may also play a structural role that influences
      substrate processing, a series of active site protease mutants has been produced
      in a cell-free protein synthesizing system via readthrough of mRNA nonsense (UAG)
      codons by chemically misacylated suppressor tRNAs. The suppressor tRNAs were
      activated with the unnatural aspartic acid analogues erythro-beta-methylaspartic
      acid, threo-beta-methylaspartic acid, or beta,beta-dimethylaspartic acid. On the
      basis of the specific activity measurements of the mutants that were produced,
      the introduction of the beta-methyl moiety was found to alter protease function
      to varying extents depending upon its orientation. While a beta-methyl group in
      the erythro orientation was the least deleterious to the specific activity of the
      protease, a beta-methyl group in the threo orientation, present in the modified
      proteins containing threo-beta-methylaspartate and beta,beta-dimethylaspartate,
      resulted in specific activities between 0 and 45% of that of the wild type
      depending upon the substrate and the substituted active site position. Titration
      studies of pH versus specific activity and inactivation studies, using an
      aspartyl protease specific suicide inhibitor, demonstrated that the mutant
      proteases maintained bell-shaped pH profiles, as well as suicide-inhibitor
      susceptibilities that are characteristic of aspartyl proteases. A molecular
      dynamics simulation of the beta-substituted aspartates in position 25 of HIV-1
      protease indicated that the threo-beta-methyl moiety may partially obstruct the
      adjacent S1' binding pocket, and also cause reorganization within the pocket,
      especially with regard to residues Val-82 and Ile-84. This finding, in
      conjunction with the biochemical studies, suggests that the active site aspartate
      residues are in proximity to the S1/S1' binding pocket and may be spatially
      influenced by the residues presented in these pockets upon substrate binding. It
      thus seems possible that the catalytic residues cooperatively interact with the
      residues that constitute the S1/S1' binding pockets and can be repositioned
      during substrate binding to orient the active site carboxylates with respect to
      the scissile amide bond, a process that likely affects the facility of
      proteolysis.

PMID- 10913289
TI  - Interaction of cardiac troponin C with Ca(2+) sensitizer EMD 57033 and cardiac
      troponin I inhibitory peptide.
AB  - The binding of Ca(2+) to cardiac troponin C (cTnC) triggers contraction in
      cardiac muscle. In diseased heart, the myocardium is often desensitized to
      Ca(2+), leading to weak cardiac contractility. Compounds that can sensitize
      cardiac muscle to Ca(2+) would have potential therapeutic value in treating heart
      failure. The thiadiazinone derivative EMD 57033 is an identified 'Ca(2+)
      sensitizer', and cTnC is a potential target of the drug. In this work, we used 2D
      ?(1)H, (15)N?-HSQC NMR spectroscopy to monitor the binding of EMD 57033 to cTnC
      in the Ca(2+)-saturated state. By mapping the chemical shift changes to the
      structure of cTnC, EMD 57033 is found to bind to the C-domain of cTnC. To test
      whether EMD 57033 competes with cardiac TnI (cTnI) for cTnC and interferes with
      the inhibitory function, we examined the interaction of cTnC with an inhibitory
      cTnI peptide (residues 128-147, cIp) in the absence and presence of EMD 57033,
      respectively. cTnC was also titrated with EMD 57033 in the presence of cIp. The
      results show that although both the drug and cIp interact with the C-domain of
      cTnC, they do not displace each other, suggesting noncompetitive binding sites
      for the two targets. Detailed chemical shift mapping of the binding sites reveals
      that the regions encompassing helix G-loop IV-helix H are more affected by EMD
      57033, while residues located on helix E-loop III-helix F and the linker between
      sites III and IV are more affected by cIp. In both cases, the binding
      stoichiometry is 1:1. The binding affinities for the drug are 8.0 +/- 1.8 and 7.4
      +/- 4.8 microM in the absence and presence of cIp, respectively, while those for
      the peptide are 78.2 +/- 10.3 and 99.2 +/- 30.0 microM in the absence and
      presence of EMD 57033, respectively. These findings suggest that EMD 57033 may
      exert its positive inotropic effect by not directly enhancing Ca(2+) binding to
      the Ca(2+) regulatory site of cTnC, but by binding to the structural domain of
      cTnC, modulating the interaction between cTnC and other thin filament proteins,
      and increasing the apparent Ca(2+) sensitivity of the contractile system.

PMID- 10913290
TI  - Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide
      transformylase.
AB  - In Escherichia coli, the PurT-encoded glycinamide ribonucleotide transformylase,
      or PurT transformylase, catalyzes an alternative formylation of glycinamide
      ribonucleotide (GAR) in the de novo pathway for purine biosynthesis. On the basis
      of amino acid sequence analyses, it is known that the PurT transformylase belongs
      to the ATP-grasp superfamily of proteins. The common theme among members of this
      superfamily is a catalytic reaction mechanism that requires ATP and proceeds
      through an acyl phosphate intermediate. All of the enzymes belonging to the ATP
      grasp superfamily are composed of three structural motifs, termed the A-, B-, and
      C-domains, and in each case, the ATP is wedged between the B- and C-domains. Here
      we describe two high-resolution X-ray crystallographic structures of PurT
      transformylase from E. coli: one form complexed with the nonhydrolyzable ATP
      analogue AMPPNP and the second with bound AMPPNP and GAR. The latter structure is
      of special significance because it represents the first ternary complex to be
      determined for a member of the ATP-grasp superfamily involved in purine
      biosynthesis and as such provides new information about the active site region
      involved in ribonucleotide binding. Specifically in PurT transformylase, the GAR
      substrate is anchored to the protein via Glu 82, Asp 286, Lys 355, Arg 362, and
      Arg 363. Key amino acid side chains involved in binding the AMPPNP to the enzyme
      include Arg 114, Lys 155, Glu 195, Glu 203, and Glu 267. Strikingly, the amino
      group of GAR that is formylated during the reaction lies at 2.8 A from one of the
      gamma-phosphoryl oxygens of the AMPPNP.

PMID- 10913291
TI  - 8-Substituted cAMP analogues reveal marked differences in adaptability, hydrogen
      bonding, and charge accommodation between homologous binding sites (AI/AII and
      BI/BII) in cAMP kinase I and II.
AB  - cAMP analogues, systematically substituted at position 8 of the adenine moiety
      (C8), were tested quantitatively for binding to each cAMP interaction site (A and
      B) of the regulatory subunits of cAMP-dependent protein kinase type I (RI) and II
      (RII). Site AII did not accommodate cAMP analogues with any bulk at position 8,
      whereas site AI accepted even bulky 8-substituents. This implies that the narrow,
      buried pocket of site AI facing position C8 of cAMP in the RI-cAMP crystal [Su,
      Y., Dostmann, W. R., Herberg, F. W., Durick, K., Xuong, N. H., Ten Eyck, L.,
      Taylor, S. S., and Varughese, K. I. (1995) Science 269, 807-813] must undergo
      considerable conformational change and still support high-affinity cAMP analogue
      binding. The B sites of RI and RII differed in three respects. First, site BI had
      a lower affinity than site BII for cAMP analogues with hydrophobic, bulky 8
      substituents. Second, site BI had a preference for substituents with hydrogen
      bonding donor potential close to C8, whereas site BII had a preference for
      substituents with hydrogen bonding acceptor potential. This implies that Tyr(371)
      of RI and the homologous Tyr(379) of RII differ in their hydrogen bonding
      preference. Third, site BI preferred analogues with a positively charged amino
      group that was an extended distance from C8, whereas site BII discriminated
      against a positive charge. The combined results allow refinement of the cAMP
      binding site geometry of RI and RII in solution, and suggest design of improved
      isozyme-specific cAMP analogues.

PMID- 10913292
TI  - Monomeric sarcosine oxidase: 1. Flavin reactivity and active site binding
      determinants.
AB  - Monomeric sarcosine oxidase (MSOX) is an inducible bacterial flavoenzyme that
      catalyzes the oxidative demethylation of sarcosine (N-methylglycine) and contains
      covalently bound FAD [8alpha-(S-cysteinyl)FAD]. This paper describes the
      spectroscopic and thermodynamic properties of MSOX as well as the X-ray
      crystallographic characterization of three new enzyme.inhibitor complexes. MSOX
      stabilizes the anionic form of the oxidized flavin (pK(a) = 8.3 versus 10.4 with
      free FAD), forms a thermodynamically stable flavin radical, and stabilizes the
      anionic form of the radical (pK(a) < 6 versus pK(a) = 8.3 with free FAD). MSOX
      forms a covalent flavin.sulfite complex, but there appears to be a significant
      kinetic barrier against complex formation. Active site binding determinants were
      probed in thermodynamic studies with various substrate analogues whose binding
      was found to perturb the flavin absorption spectrum and inhibit MSOX activity.
      The carboxyl group of sarcosine is essential for binding since none is observed
      with simple amines. The amino group of sarcosine is not essential, but binding
      affinity depends on the nature of the substitution (CH(3)XCH(2)CO(2)(-), X =
      CH(2) < O < S < Se < Te), an effect which has been attributed to differences in
      the strength of donor-pi interactions. MSOX probably binds the zwitterionic form
      of sarcosine, as judged by the spectrally similar complexes formed with
      dimethylthioacetate [(CH(3))(2)S(+)CH(2)CO(2)(-)] and dimethylglycine (K(d) =
      20.5 and 17.4 mM, respectively) and by the crystal structure of the latter. The
      methyl group of sarcosine is not essential but does contribute to binding
      affinity. The methyl group contribution varied from -3.79 to -0.65 kcal/mol with
      CH(3)XCH(2)CO(2)(-) depending on the nature of the heteroatom (NH(2)(+) > O > S)
      and appeared to be inversely correlated with heteroatom electron density. Charge
      transfer complexes are formed with MSOX and CH(3)XCH(2)CO(2)(-) when X = S, Se,
      or Te. An excellent linear correlation is observed between the energy of the
      charge transfer bands and the one-electron reduction potentials of the ligands.
      The presence of a sulfur, selenium, or telurium atom identically positioned with
      respect to the flavin ring is confirmed by X-ray crystallography, although the
      increased atomic radius of S < Se < Te appears to simultaneously favor an
      alternate binding position for the heavier atoms. Although L-proline is a poor
      substrate, aromatic heterocyclic carboxylates containing a five-membered ring and
      various heteroatoms (X = NH, O, S) are good ligands (K(d, X=NH) = 1.37 mM) and
      form charge-transfer complexes with MSOX. The energy of the charge-transfer bands
      (S > O >> NH) is linearly correlated with the one-electron ionization potentials
      of the corresponding heterocyclic rings.

PMID- 10913293
TI  - Monomeric sarcosine oxidase: 2. Kinetic studies with sarcosine, alternate
      substrates, and a substrate analogue.
AB  - Monomeric sarcosine oxidase (MSOX) is a flavoenzyme that catalyzes the oxidative
      demethylation of sarcosine (N-methylglycine) to yield glycine, formaldehyde, and
      hydrogen peroxide. MSOX can oxidize other secondary amino acids (N-methyl-L
      alanine, N-ethylglycine, and L-proline), but N,N-dimethylglycine, a tertiary
      amine, is not a substrate. N-Methyl-L-alanine is a good alternate substrate,
      exhibiting a k(cat) value (8700 min(-)(1)) similar to sarcosine (7030 min(-)(1)).
      Turnover with L-proline (k(cat) = 25 min(-)(1)) at 25 degrees C occurs at less
      than 1% of the rate observed with sarcosine. MSOX is converted to a two-electron
      reduced form upon anaerobic reduction with sarcosine or L-proline. No evidence
      for a spectrally detectable intermediate was obtained in reductive half-reaction
      studies with L-proline. The reductive half-reaction with L-proline at 4 degrees C
      exhibited saturation kinetics (k(lim) = 6.0 min(-)(1), K(d) = 260 mM) and other
      features consistent with a mechanism in which a practically irreversible
      reduction step (E(ox). S --> E(red).P) with a rate constant, k(lim), is preceded
      by a rapidly attained equilibrium (K(d)) between free E and the E.S complex.
      Steady-state kinetic studies with sarcosine and N-methyl-L-alanine in the absence
      or presence of a dead-end inhibitor (pyrrole-2-carboxylate) indicate that
      catalysis proceeds via a "modified" ping pong mechanism in which oxygen reacts
      with E(red).P prior to the dissociation of the imino acid product. In this
      mechanism, double reciprocal plots will appear nearly parallel (as observed) if
      the reduction step is nearly irreversible. A polar mechanism, involving formation
      of a covalent 4a-flavin-substrate adduct is one of several plausible mechanisms
      for sarcosine oxidation. Thiols are known to form similar 4a-flavin adducts. MSOX
      does not form a 4a-adduct with thioglycolate but does form a charge-transfer
      complex that undergoes an unanticipated one-electron-transfer reaction to yield
      the anionic flavin radical.

PMID- 10913294
TI  - Molecular basis for complex formation between methylamine dehydrogenase and
      amicyanin revealed by inverse mutagenesis of an interprotein salt bridge.
AB  - Methylamine dehydrogenase (MADH) and amicyanin form a physiologic complex which
      is required for interprotein electron transfer. The crystal structure of this
      protein complex is known, and the importance of certain residues on amicyanin in
      its interaction with MADH has been demonstrated by site-directed mutagenesis. In
      this study, site-directed mutagenesis of MADH, kinetic data, and thermodynamic
      analysis are used to probe the molecular basis for stabilization of the protein
      complex by an interprotein salt bridge between Arg99 of amicyanin and Asp180 of
      the alpha subunit of MADH. This paper reports the first site-directed mutagenesis
      of MADH, as well as the construction, heterologous expression, and
      characterization of a six-His-tagged MADH. alpha Asp180 of MADH was converted to
      arginine to examine the effect on complex formation with native and mutant
      amicyanins. This mutation had no effect on the parameters for methylamine
      oxidation by MADH, but significantly affected its interaction with amicyanin. Of
      the native and mutant proteins that were studied, their observed order of
      affinity for each other was as follows: native MADH and native amicyanin > native
      MADH and R99D amicyanin > alpha D180R MADH and native amicyanin > alpha D180R
      MADH and R99D amicyanin, and alpha D180R MADH and R99L amicyanin. The alpha D180R
      mutation also eliminated the ionic strength dependence of the reaction of MADH
      with amicyanin that is observed with wild-type MADH. Interestingly, the inverse
      mutation pair of alpha D180R MADH and R99D amicyanin did not restore the
      favorable salt bridge, but instead disrupted complex formation much more severely
      than did either individual mutation. These results are explained using molecular
      modeling and thermodynamic analysis of the kinetic data to correlate the energy
      contributions of specific stabilizing and destabilizing interactions that are
      present in the wild-type and mutant complexes. A model is also proposed to
      describe the sequence of events that leads to stable complex formation between
      MADH and amicyanin.

PMID- 10913295
TI  - Recognition of chitooligosaccharides and their N-acetyl groups by putative
      subsites of chitin deacetylase from a deuteromycete, Colletotrichum
      lindemuthianum.
AB  - The reaction pattern of an extracellular chitin deacetylase from a Deuteromycete,
      Colletotrichum lindemuthianum ATCC 56676, was investigated by use of
      chitooligosaccharides [(GlcNAc)(n)(), n = 3-6] and partially N-deacetylated
      chitooligosaccharides as substrates. When 0.5% of (GlcNAc)(n)() was deacetylated,
      the corresponding monodeacetylated products were initially detected without any
      processivity, suggesting the involvement of a multiple-chain mechanism for the
      deacetylation reaction. The structural analysis of these first-step products
      indicated that the chitin deacetylase strongly recognizes a sequence of four N
      acetyl-D-glucosamine (GlcNAc) residues of the substrate (the subsites for the
      four GlcNAc residues are defined as -2, -1, 0, and +1, respectively, from the
      nonreducing end to the reducing end), and the N-acetyl group in the GlcNAc
      residue positioned at subsite 0 is exclusively deacetylated. When substrates of a
      low concentration (100 microM) were deacetylated, the initial deacetylation rate
      for (GlcNAc)(4) was comparable to that of (GlcNAc)(5), while deacetylation of
      (GlcNAc)(3) could not be detected. Reaction rate analyses of partially N
      deacetylated chitooligosaccharides suggested that subsite -2 strongly recognizes
      the N-acetyl group of the GlcNAc residue of the substrate, while the
      deacetylation rate was not affected when either subsite -1 or +1 was occupied
      with a D-glucosamine residue instead of GlcNAc residue. Thus, the reaction
      pattern of the chitin deacetylase is completely distinct from that of a
      Zygomycete, Mucor rouxii, which produces a chitin deacetylase for accumulation of
      chitosan in its cell wall.

PMID- 10913296
TI  - Binding site analysis of cellulose binding domain CBD(N1) from endoglucanse C of
      Cellulomonas fimi by site-directed mutagenesis.
AB  - Endoglucanase C (CenC), a beta1,4 glucanase from the soil bacterium Cellulomonas
      fimi, binds to amorphous cellulose via two homologous cellulose binding domains,
      termed CBD(N1) and CBD(N2). In this work, the contributions of 10 amino acids
      within the binding cleft of CBD(N1) were evaluated by single site-directed
      mutations to alanine residues. Each isolated domain containing a single mutation
      was analyzed for binding to an insoluble amorphous preparation of cellulose,
      phosphoric acid swollen Avicel (PASA), and to a soluble glucopyranoside polymer,
      barley beta-glucan. The effect of any given mutation on CBD binding was similar
      for both substrates, suggesting that the mechanism of binding to soluble and
      insoluble substrates is the same. Tyrosines 19 and 85 were essential for tight
      binding by CBD(N1) as their replacement by alanine results in affinity decrements
      of approximately 100-fold on PASA, barley beta-glucan, and soluble
      cellooligosaccharides. The tertiary structures of unbound Y19A and Y85A were
      assessed by heteronuclear single quantum coherence (HSQC) spectroscopy. These
      studies indicated that the structures of both mutants were perturbed but that all
      perturbations are very near to the site of mutation.

PMID- 10913297
TI  - Enzymatic synthesis of 1,3,6,8-tetrahydroxynaphthalene solely from malonyl
      coenzyme A by a fungal iterative type I polyketide synthase PKS1.
AB  - The Colletotrichum lagenarium PKS1 gene encoding iterative type I polyketide
      synthase of 1,3,6,8-tetrahydroxynaphthalene (T4HN) was overexpressed in
      Aspergillus oryzae. SDS-PAGE analysis of the cell-free extract prepared from the
      transformant showed an intense band of 230000 which corresponded to the molecular
      weight of the deduced PKS1 protein. By using this cell-free extract, in vitro
      synthesis of T4HN was successfully confirmed as the first example of the fungal
      multi-aromatic ring polyketide synthase activity ever detected. To identify the
      starter unit for T4HN synthesis, (14)C-labeled acetyl CoA and/or (14)C-labeled
      malonyl CoA were used as substrates for T4HN synthase reaction. Observed was the
      incorporation of (14)C label into T4HN solely from malonyl CoA even in the
      absence of acetyl CoA and not from acetyl CoA. This in vitro result unambiguously
      identified that malonyl CoA serves as the starter as well as extender units in
      the formation of T4HN by fungal polyketide synthase PKS1.

PMID- 10913298
TI  - Attachment of the N-terminal domain of Salmonella typhimurium AhpF to Escherichia
      coli thioredoxin reductase confers AhpC reductase activity but does not affect
      thioredoxin reductase activity.
AB  - AhpF of Salmonella typhimurium, the flavoprotein reductase required for catalytic
      turnover of AhpC with hydroperoxide substrates in the alkyl hydroperoxide
      reductase system, is a 57 kDa protein with homology to thioredoxin reductase
      (TrR) from Escherichia coli. Like TrR, AhpF employs tightly bound FAD and redox
      active disulfide center(s) in catalyzing electron transfer from reduced pyridine
      nucleotides to the disulfide bond of its protein substrate. Homology of AhpF to
      the smaller (35 kDa) TrR protein occurs in the C-terminal part of AhpF; a stretch
      of about 200 amino acids at the N-terminus of AhpF contains an additional redox
      active disulfide center and is required for catalysis of AhpC reduction. We have
      demonstrated that fusion of the N-terminal 207 amino acids of AhpF to full-length
      TrR results in a chimeric protein (Nt-TrR) with essentially the same catalytic
      efficiency (k(cat)/K(m)) as AhpF in AhpC reductase assays; both k(cat) and the
      K(m) for AhpC are decreased about 3-4-fold for Nt-TrR compared with AhpF. In
      addition, Nt-TrR retains essentially full TrR activity. Based on results from two
      mutants of Nt-TrR (C129, 132S and C342,345S), AhpC reductase activity requires
      both centers while TrR activity requires only the C-terminal-most disulfide
      center in Nt-TrR. The high catalytic efficiency with which Nt-TrR can reduce
      thioredoxin implies that the attached N-terminal domain does not block access of
      thioredoxin to the TrR-derived Cys342-Cys345 center of Nt-TrR nor does it impede
      the putative conformational changes that this part of Nt-TrR is proposed to
      undergo during catalysis. These studies indicate that the C-terminal part of AhpF
      and bacterial TrR have very similar mechanistic properties. These findings also
      confirm that the N-terminal domain of AhpF plays a direct role in AhpC reduction.

PMID- 10913299
TI  - Oligomerization of mouse alpha 1-syntrophin and self-association of its
      pleckstrin homology domain 1 containing sequences.
AB  - Syntrophins are known to self-associate to form oligomers. Mouse alpha 1
      syntrophin sequences were produced as chimeric fusion proteins in bacteria and
      were found to also oligomerize and in a micromolar Ca(2+)-dependent manner. The
      oligomerization was localized to the N-terminal pleckstrin homology domain (PH1)
      or adjacent sequences; the second, C-terminal PH2 domain did not show
      oligomerization. PH1 was found to self-associate, and calmodulin or Ca(2+)
      chelating agents such as ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'
      tetraacetic acid (EGTA) could effectively prevent this oligomerization. A single
      calmodulin bound per syntrophin to cause inhibition of the precipitation. Since
      calmodulin inhibited syntrophin oligomerization in the presence or absence of
      Ca(2+), Ca(2+) binding to syntrophin is responsible for the inhibition by EGTA of
      syntrophin oligomerization.

PMID- 10913300
TI  - The N-terminal fragment of human parathyroid hormone receptor 1 constitutes a
      hormone binding domain and reveals a distinct disulfide pattern.
AB  - The N-terminal extracellular parts of human G-protein coupled receptor class B,
      for example, receptors for secretin, glucagon, or parathyroid hormone, are
      involved in ligand binding. To obtain structural and functional information on
      the N-terminal receptor fragment of human parathyroid hormone receptor 1 (PTHR1),
      the truncated receptor was expressed in the cytosol of Escherichia coli in the
      form of inclusion bodies. Oxidative refolding of inclusion body material resulted
      in stable, soluble, monomeric protein. Ligand binding was proved by surface
      plasmon resonance spectroscopy and isothermal titration calorimetry. Refolded
      receptor fragment was able to bind parathyroid hormone with an apparent
      dissociation constant of 3-5 microM. Far-UV circular dichroism spectra showed
      that the refolded polypeptide contained approximately 25% alpha-helical and 23%
      beta-sheet secondary structures. Analysis of the disulfide bond pattern of the
      refolded receptor fragment revealed disulfide bonds between Cys170 and Cys131,
      Cys148 and Cys108, and Cys117 and Cys48. These results demonstrate that the
      extracellular N-terminal domain of the parathyroid hormone receptor (PTHR1)
      possesses a well-defined, stable conformation, which shows a significant ligand
      binding activity.

PMID- 10913301
TI  - Structural determinants for activity of glucagon-like peptide-2.
AB  - Glucagon-like peptide-2 (GLP-2) is a 33 amino acid gastrointestinal hormone that
      regulates epithelial growth in the intestine. Dipeptidylpeptidase IV cleaves GLP
      2 at the position 2 alanine, resulting in the inactivation of peptide activity.
      To understand the structural basis for GLP-2 action, we studied receptor binding
      and activation for 56 GLP-2 analogues with either position 2 substitutions or
      alanine replacements along the length of the peptide. The majority of position 2
      substitutions exhibited normal to enhanced GLP-2 receptor (GLP-2R) binding; in
      contrast, position 2 substitutions were less well tolerated in studies of
      receptor activation as only Gly, Ile, Pro, alpha-aminobutyric acid, D-Ala, or nor
      Val substitutions exhibited enhanced GLP-2R activation. In contrast, alanine
      replacement at positions 5,6,17, 20, 22, 23, 25, 26, 30, and 31 led to diminished
      GLP-2R binding. Position 2 substitutions containing Asp, Leu, Lys, Met, Phe, Trp,
      and Tyr, and Ala substitutions at positions 12 and 21 exhibited normal to
      enhanced GLP-2R binding but greater than 75% reduction in receptor activation. D
      Ala(2), Pro(2) and Gly(2), Ala(16) exhibited significantly lower EC(50)s for
      receptor activation than the parent peptide (p < 0.01-0.001). Circular dichroism
      analysis indicated that the enhanced activity of these GLP-2 analogues was
      independent of the alpha-helical content of the peptide. These results indicate
      that single amino acid substitutions within GLP-2 can confer structural changes
      to the ligand-receptor interface, allowing the identification of residues
      important for GLP-2R binding and receptor activation.

PMID- 10913302
TI  - The molecular origin of the inhibition of transducin activation in rhodopsin
      lacking the 9-methyl group of the retinal chromophore: a UV-Vis and FTIR
      spectroscopic study.
AB  - The formation of the active rhodopsin state metarhodopsin II (MII) is believed to
      be partially governed by specific steric constraints imposed onto the protein by
      the 9-methyl group of the retinal chromophore. We studied the properties of the
      synthetic pigment 9-demethyl rhodopsin (9dm-Rho), consisting of the rhodopsin
      apoprotein regenerated with synthetic retinal lacking the 9-methyl group, by UV
      vis and Fourier transform infrared difference spectroscopy. Low activation rates
      of the visual G-protein transducin by the modified pigment reported in previous
      studies are shown to not be caused by the reduced activity of its MII state, but
      to be due to a dramatic equilibrium shift from MII to its immediate precursor,
      MI. The MII state of 9dm-Rho displays only a partial deprotonation of the retinal
      Schiff base, leading to the formation of two MII subspecies absorbing at 380 and
      470 nm, both of which seem to be involved in transducin activation. The rate of
      MII formation is slowed by 2 orders of magnitude compared to rhodopsin. The dark
      state and the MI state of 9dm-Rho are distinctly different from their respective
      states in the native pigment, pointing to a more relaxed fit of the retinal
      chromophore in its binding pocket. The shifted equilibrium between MI and MII is
      therefore discussed in terms of an increased entropy of the 9dm-Rho MI state due
      to changed steric interactions.

PMID- 10913303
TI  - Sequence-specific DNA binding by the glucocorticoid receptor DNA-binding domain
      is linked to a salt-dependent histidine protonation.
AB  - We used isothermal titration calorimetry in the temperature range 21-25 degrees C
      to investigate the effect of pH on the calorimetric enthalpy (delta H(cal)) for
      sequence specific DNA-binding of the glucocorticoid receptor DNA-binding domain
      (GR DBD). Titrations were carried out in solutions containing 100 mM NaCl, 1 mM
      dithiothreitol, 5% glycerol by volume, and 20 mM Tris, Hepes, Mops, or sodium
      phosphate buffers at pH 7.5. A strong dependence of delta H(cal) on the buffer
      ionization enthalpy is observed, demonstrating that the DNA binding of the GR DBD
      is linked to proton uptake at these conditions. The apparent increase in the
      pK(a) for an amino acid side chain upon DNA binding is supported by the results
      of complementary titrations, where delta H(cal) shows a characteristic dependence
      on the solution pH. delta H(cal) is also a function of the NaCl concentration,
      with opposite dependencies in Tris and Hepes buffers, respectively, such that a
      similar delta H(cal) value is approached at 300 mM NaCl. This behavior shows that
      the DNA-binding induced protonation is inhibited by increased concentrations of
      NaCl. A comparison with structural data suggests that the protonation involves a
      histidine (His451) in the GR DBD, because in the complex this residue is located
      close to a DNA phosphate at an orientation that is consistent with a charged
      charged hydrogen bond in the protonated state. NMR spectra show that His451 is
      not protonated in the unbound protein at pH 7.5. The pH dependence in delta
      H(cal) can be quantitatively described by a shift of the pK(a) of His451 from
      approximately 6 in the unbound state to close to 8 when bound to DNA at low salt
      concentration conditions. A simple model involving a binding competition between
      a proton and a Na(+) counterion to the GR DBD-DNA complex reproduces the
      qualitative features of the salt dependence.

PMID- 10913304
TI  - Ets domain transcription factor PE1 suppresses human interstitial collagenase
      promoter activity by antagonizing protein-DNA interactions at a critical AP1
      element.
AB  - In MC3T3E1 calvarial osteoblasts, fibroblast growth factor receptor (FGFR)
      signaling elicits multiple transcriptional responses, including upregulation of
      the interstitial collagenase/matrix metalloproteinase 1 (MMP1) promoter. FGF
      responsiveness maps to a bipartite Ets/AP1 element at base pairs -123 to -61 in
      the human MMP1 promoter. Under basal conditions, the MMP1 promoter is repressed
      in part via protein-DNA interactions at the Ets cognate, and minimally two
      mechanisms convey MMP1 promoter upregulation by FGF2: (a) transcriptional
      activation via Fra1/c-Jun containing DNA-protein interactions at the AP1 cognate
      and (b) derepression of promoter activity regulated by the Ets cognate. To
      identify osteoblast Ets repressors that potentially participate in gene
      expression in the osteoblast, we performed reverse transcription-polymerase chain
      reaction (RT-PCR) analysis of mRNA isolated from MC3T3E1 cells, using
      degenerative amplimers to the conserved Ets DNA binding domain to survey the Ets
      genes expressed by these cells. Six distinct Ets mRNAs were identified: Ets2,
      Fli1, GABPalpha, SAP1, Elk1, and PE1. Of these, only PE1 has extensive homology
      to the known Ras-regulated Ets transcriptional repressor, ERF. Therefore, we
      cloned and characterized PE1 cDNA from a mouse brain library and performed
      functional analysis of this particular Ets family member. A 2 kb transcript was
      isolated from brain that encodes a approximately 57 kDa protein; the predicted
      protein contains the known N-terminal Ets domain of PE1 and a novel C-terminal
      domain with signficant homology to murine ERF. The murine PE1 open reading frame
      (ORF) is much larger than the previously reported human PE1 ORF. Consistent with
      this, affinity-purified rabbit anti-mouse PE1 antibody specifically recognizes an
      approximately 66 kDa protein present only in the nuclear fraction of MC3T3E1
      osteoblasts. Recombinant PE1 binds authentic AGGAWG Ets DNA cognates, and
      transient transfection studies demonstrate that PE1 represses MMP1 promoter
      activity. Surprisingly, although deletion of the MMP1 Ets cognate at nucleotides 
      88 to -83 abrogates FGF2 induction, it does not prevent suppression of the AP1
      dependent MMP1 promoter by PE1. PE1 regulation maps to the MMP1 promoter region 
      75 to -61, suggesting that PE1 suppresses transcription via protein-protein
      interactions with AP1. Consistent with this, recombinant GST-PE1 specifically
      inhibits the formation of protein-DNA interactions on the MMP1 AP1 site (-72 to 
      66) when present in an admixture with MC3T3E1 crude nuclear extract. In toto,
      these data indicate that PE1 participates in the transcriptional regulation of
      the MMP1 promoter in osteoblasts. As observed with other transcriptional
      repressors of MMP1 gene expression, transcriptional suppression by PE1 occurs via
      inhibition of AP1-dependent promoter activity.

PMID- 10913305
TI  - Assembly of Saccharomyces cerevisiae ribosomal stalk: binding of P1 proteins is
      required for the interaction of P2 proteins.
AB  - The yeast ribosomal stalk is formed by a protein pentamer made of the 38 kDa P0
      and four 12 kDa acidic P1/P2. The interaction of recombinant acidic proteins P1
      alpha and P2 beta with ribosomes from Saccharomyces cerevisiae D4567, lacking all
      the 12 kDa stalk components, has been used to study the in vitro assembly of this
      important ribosomal structure. Stimulation of the ribosome activity was obtained
      by incubating simultaneously the particles with both proteins, which were
      nonphosphorylated initially and remained unmodified afterward. The N-terminus
      state, free or blocked, did not affect either the binding or reactivating
      activity of both proteins. Independent incubation with each protein did not
      affect the activity of the particles, however, protein P2 beta alone was unable
      to bind the ribosome whereas P1 alpha could. The binding of P1 alpha alone is a
      saturable process in acidic-protein-deficient ribosomes and does not take place
      in complete wild-type particles. Binding of P1 proteins in the absence of P2
      proteins takes also place in vivo, when protein P1 beta is overexpressed in S.
      cerevisiae. In contrast, protein P2 beta is not detected in the ribosome in the
      P1-deficient D67 strain despite being accumulated in the cytoplasm. The results
      confirm that neither phosphorylation nor N-terminal blocking of the 12 kDa acidic
      proteins is required for the assembly and function of the yeast stalk. More
      importantly, and regardless of the involvement of other elements, they indicate
      that stalk assembling is a coordinated process, in which P1 proteins would
      provide a ribosomal anchorage to P2 proteins, and P2 components would confer
      functionality to the complex.

PMID- 10913306
TI  - Structural differences between Saccharomyces cerevisiae ribosomal stalk proteins
      P1 and P2 support their functional diversity.
AB  - The eukaryotic acidic P1 and P2 proteins modulate the activity of the ribosomal
      stalk but playing distinct roles. The aim of this work was to analyze the
      structural features that are behind their different function. A structural
      characterization of Saccharomyces cerevisaie P1 alpha and P2 beta proteins was
      performed by circular dichroism, nuclear magnetic resonance, fluorescence
      spectroscopy, thermal denaturation, and protease sensitivity. The results confirm
      the low structure present in both proteins but reveal clear differences between
      them. P1 alpha shows a virtually unordered secondary structure with a residual
      helical content that disappears below 30 degrees C and a clear tendency to
      acquire secondary structure at low pH and in the presence of trifluoroethanol. In
      agreement with this higher disorder P1 alpha has a fully solvent-accessible
      tryptophan residue and, in contrast to P2 beta, is highly sensitive to protease
      degradation. An interaction between both proteins was observed, which induces an
      increase in the global secondary structure content of both proteins. Moreover,
      mixing of both proteins causes a shift of the P1 alpha tryptophan 40 signal,
      pointing to an involvement of this region in the interaction. This evidence
      directly proves an interaction between P1 alpha and P2 beta before ribosome
      binding and suggests a functional complementation between them. On a whole, the
      results provide structural support for the different functional roles played by
      the proteins of the two groups showing, at the same time, that relatively small
      structural differences between the two stalk acidic protein types can result in
      significant functional changes.

PMID- 10913307
TI  - Expression and mutagenesis of the novel serpin endopin 2 demonstrates a
      requirement for cysteine-374 for dithiothreitol-sensitive inhibition of elastase.
AB  - The primary sequence of the serpin endopin 2 predicts a reactive site loop (RSL)
      region that possesses high homology to bovine elastase inhibitor, suggesting
      inhibition of elastase. Moreover, endopin 2 possesses two cysteine residues that
      implicate roles for reduced Cys residue(s) for inhibitory activity. To test these
      predicted properties, mutagenesis and chemical modification of recombinant
      endopin 2 were performed to examine the influence of dithiothreitol (DTT), a
      reducing agent, on endopin 2 activity. Endopin 2 inhibited elastase in a DTT
      dependent manner, with enhanced inhibition in the presence of DTT. The
      stoichiometry of inhibition in the presence of DTT occurred at a molar ratio of
      endopin 2 to elastase of 8/1, resulting in complete inhibition of elastase.
      However, a higher molar ratio (25/1) was required in the absence of DTT. DTT
      enhanced the formation of SDS-stable complexes of endopin 2 and elastase, a
      characteristic property of serpins. Site-directed mutagenesis of endopin 2, with
      substitution of Ala for Cys-232 or Cys-374, demonstrated that Cys-374 (but not
      Cys-232) was required for the DTT-sensitive nature of endopin 2. Chemical
      modification of Cys-374 by bis(maleimido)ethane also reduced inhibitory activity.
      Modified electrophoretic mobilities of mutant endopin 2 suggested the presence of
      intramolecular disulfide bonds; in addition, chemical modification suggested that
      Cys-374 influences the electrophoretic and conformational properties of endopin
      2. Moreover, the reducing agent glutathione enhanced endopin 2 activity,
      suggesting that glutathione can function as an endogenous reducing agent for
      endopin 2 in vivo. These findings demonstrate the importance of Cys-374 for DTT
      sensitive inhibition of elastase by endopin 2.

PMID- 10913308
TI  - Discrimination of pheromone enantiomers by two pheromone binding proteins from
      the gypsy moth Lymantria dispar.
AB  - The gypsy moth, Lymantria dispar, uses (7R, 8S)-cis-2-methyl-7, 8
      epoxyoctadecane, (+)-disparlure, as a sex pheromone. The (-) enantiomer of the
      pheromone is a strong behavioral antagonist. Specialized sensory hairs,
      sensillae, on the antennae of male moths detect the pheromone. Once the pheromone
      enters a sensillum, the very abundant pheromone binding protein (PBP) transports
      the odorant to the sensory neuron. We have expressed the two PBPs found in gypsy
      moth antennae, PBP1 and PBP2, and we have studied the affinity of these
      recombinant PBPs for the enantiomers of disparlure. To study pheromone binding
      under equilibrium conditions, we developed and validated a binding assay. We have
      addressed the two major problems with hydrophobic ligands in aqueous solution:
      (1) concentration-dependent adsorption of the ligand on vial surfaces and (2)
      separation of the protein-bound ligand from the material remaining free in
      solution. We used this assay to demonstrate for the first time that pheromone
      binding to PBP is reversible and that the two PBPs from L. dispar differ in their
      enantiomer binding preference. PBP1 has a higher affinity for the (-) enantiomer,
      while PBP2 has a higher affinity for the (+) enantiomer. The PBP from the wild
      silk moth, Antheraea polyphemus (Apol-3) bound the disparlure enantiomers more
      weakly than either of the L. dispar PBPs, but Apol-3 was also able to
      discriminate the enantiomers. We have observed extensive aggregation of both L.
      dispar PBPs and an increase in pheromone binding at high (>2 microM) PBP
      concentrations. We present a model of disparlure binding to the two PBPs.

PMID- 10913309
TI  - Functional conservation of the active sites of human and Drosophila angiotensin I
      converting enzyme.
AB  - Human somatic angiotensin I-converting enzyme (sACE) has two active sites present
      in two homologous protein domains, resulting from a tandem gene duplication. It
      has been proposed that the N- and C-terminal active sites can have specific in
      vivo roles. In Drosophila melanogaster, Ance and Acercode for two ACE-like single
      domain proteins, also predicted to have distinct physiological roles. We have
      investigated the relationship of Ance and Acer to the N- and C-domains of human
      sACE by genomic sequence analysis and by using domain-selective inhibitors,
      including RXP 407, a selective inhibitor of the human N-domain. These phosphinic
      peptides were potent inhibitors of Acer, but not of Ance. We conclude that the
      active sites of the N-domain and of Acer share structural features that permit
      the binding of the unusual RXP407 inhibitor and the hydrolysis of a broader range
      of peptide structures. In comparison, Ance, like the human C-domain of ACE,
      displays greater inhibitor selectivity. From the analysis of the published
      sequence of the Adh region of Drosophila chromosome 2, which carries Ance, Acer,
      and four additional ACE-like genes, we also suggest that this functional
      conservation is reflected in an ancestral gene structure identifiable in both
      protostome and deuterostome lineages and that the duplication seen in vertebrate
      genomes predates the divergence of these lineages. The conservation of ACE
      enzymes with distinct active sites in the evolution of both vertebrate and
      invertebrate species provides further evidence that these two kinds of active
      sites have different physiological functions.

PMID- 10913310
TI  - Nuclear magnetic resonance spectroscopy and molecular modeling reveal that
      different hydrogen bonding patterns are possible for G.U pairs: one hydrogen bond
      for each G.U pair in r(GGCGUGCC)(2) and two for each G.U pair in r(GAGUGCUC)(2).
AB  - G.U pairs occur frequently and have many important biological functions. The
      stability of symmetric tandem G.U motifs depends both on the adjacent Watson
      Crick base pairs, e.g., 5'G > 5'C, and the sequence of the G.U pairs, i.e., 5'-UG
      3' > 5'-GU-3', where an underline represents a nucleotide in a G.U pair [Wu, M.,
      McDowell, J. A., and Turner, D. H. (1995) Biochemistry 34, 3204-3211]. In
      particular, at 37 degrees C, the motif 5'-CGUG-3' is less stable by approximately
      3 kcal/mol compared with other symmetric tandem G.U motifs with G-C as adjacent
      pairs: 5'-GGUC-3', 5'-GUGC-3', and 5'-CUGG-3'. The solution structures of
      r(GAGUGCUC)(2) and r(GGCGUGCC)(2) duplexes have been determined by NMR and
      restrained simulated annealing. The global geometry of both duplexes is close to
      A-form, with some distortions localized in the tandem G.U pair region. The
      striking discovery is that in r(GGCGUGCC)(2) each G.U pair apparently has only
      one hydrogen bond instead of the two expected for a canonical wobble pair. In the
      one-hydrogen-bond model, the distance between GO6 and UH3 is too far to form a
      hydrogen bond. In addition, the temperature dependence of the imino proton
      resonances is also consistent with the different number of hydrogen bonds in the
      G.U pair. To test the NMR models, U or G in various G.U pairs were individually
      replaced by N3-methyluridine or isoguanosine, respectively, thus eliminating the
      possibility of hydrogen bonding between GO6 and UH3. The results of thermal
      melting studies on duplexes with these substitutions support the NMR models.

PMID- 10913311
TI  - Molecular recognition of cAMP by an RNA aptamer.
AB  - Two classes of RNA aptamers that bind the second messenger adenosine 3',5'-cyclic
      monophosphate (cAMP; 1) were isolated from a random-sequence pool using in vitro
      selection. Class I and class II aptamers are formed by 33- and 31-nucleotide
      RNAs, respectively, and each is comprised of similar stem-loop and single
      stranded structural elements. Class II aptamers, which dominate the final
      selected RNA population, require divalent cations for complex formation and
      display a dissociation constant (K(D)) for cAMP of approximately 10 microM. A
      representative class II aptamer exhibits substantial discrimination against 5'-
      and 3'-phosphorylated nucleosides such as ATP, 5'-AMP, and 3'-AMP. However,
      components of cAMP such as adenine and adenosine also are bound, indicating that
      the adenine moiety is the primary positive determinant of ligand binding.
      Specificity of cAMP binding appears to be established by hydrogen bonding
      interactions with the adenine base as well as by steric interactions with groups
      on the ribose moiety. In addition, the aptamer recognizes 8,5'-O-cycloadenosine
      (2) but not N(3), 5'-cycloadenosine (3), indicating that this RNA might
      selectively recognize the anti conformation of the N-glycosidic bond of cAMP.

PMID- 10913312
TI  - Role of calnexin, calreticulin, and endoplasmic reticulum mannosidase I in
      apolipoprotein(a) intracellular targeting.
AB  - Apolipoprotein(a) [apo(a)] is a component of atherogenic lipoprotein(a) [Lp(a)].
      Differences in the extent of endoplasmic reticulum (ER) associated degradation
      (ERAD) of apo(a) allelic variants contribute to the >1000-fold variation in
      plasma Lp(a) levels. Using human apo(a) transgenic mouse hepatocytes, we analyzed
      the role of the ER chaperones calnexin (CNX) and calreticulin (CRT), and ER
      mannosidase I in apo(a) intracellular targeting. Co-immunoprecipitation and pulse
      chase analyses revealed similar kinetics of apo(a) interaction with CNX and CRT,
      peaking 15-30 min after apo(a) synthesis. Trapping of apo(a) N-linked glycans in
      their monoglucosylated form, by posttranslational inhibition of ER glucosidase
      activity with castanospermine (CST), enhanced apo(a)-CNX/CRT interaction and
      prevented both apo(a) secretion and ERAD. Delay of CST addition until 20 or 30
      min after apo(a) synthesis [when no apo(a) had yet undergone degradation or Golgi
      specific carbohydrate modification] allowed a portion of apo(a) to be secreted or
      degraded. These results are consistent with a transient apo(a)-CNX/CRT
      association and suggest that events downstream of CNX/CRT interaction determine
      apo(a) intracellular targeting. Inhibition of ER mannosidase I with
      deoxymannojirimycin or kifunensine had no effect on apo(a) secretion, but
      inhibited proteasome-mediated apo(a) ERAD even under conditions where apo(a)
      CNX/CRT interaction was prevented. These results suggest a role for an
      additional, mannose-specific, ER lectin in targeting secretory proteins to the
      proteasome for destruction.

PMID- 10913313
TI  - Differential interaction of tubulin isotypes with the antimitotic compound IKP
      104.
AB  - The tubulin molecule is a heterodimer composed of two polypeptide chains,
      designated alpha and beta; both alpha and beta exist in numerous isotypic forms,
      which differ in their assembly and drug binding properties. 2-(4-Fluorophenyl)-1
      (2-chloro-3, 5-dimethoxyphenyl)-3-methyl-6-phenyl-4(1H)-pyridinone (IKP-104) is
      an antimitotic compound which inhibits polymerization and induces
      depolymerization of microtubules [Mizuhashi, F., et al. (1992) Jpn. J. Cancer
      Res. 83, 211]. Since the previous work was undertaken with isotypically
      unfractionated tubulin, we have investigated the interactions of IKP-104 with the
      isotypically purified tubulin dimers (alpha beta(II), alpha beta(III), and alpha
      beta(IV)). We find that IKP-104 binds to alpha beta(II) and alpha beta(III) at
      two classes of binding sites. However, affinities for each class of site are much
      weaker for alpha beta(III) than for alpha beta(II). Interestingly, the low
      affinity site on alpha beta(IV) was not detectable. Its high-affinity site was
      weaker than those of either alpha beta(II) or alpha beta(III). In a pattern
      consistent with these results, IKP-104 inhibited assembly better with alpha
      beta(II) than with the other two dimers. Higher concentrations of IKP-104 induced
      formation of spiral aggregates from alpha beta(II) and alpha beta(III) but not
      from alpha beta(IV). Our results suggest that the interaction of IKP-104 with
      tubulin isotypes is very complex: alpha beta(II) and alpha beta(III) differ
      quantitatively in their interaction with IKP-104, and alpha beta(IV)'s
      interaction differs both quantitatively and qualitatively from those of the other
      two dimers.

PMID- 10913314
TI  - Converting a c-type to a b-type cytochrome: Met61 to His61 mutant of Pseudomonas
      cytochrome c-551.
AB  - The gene nirM, coding for cytochrome c-551 in Pseudomonas stutzeri substrain
      ZoBell, was engineered to mutate Met61, the sixth ligand to the heme c, into
      His61, thereby converting the typical Met-His coordination of a c-type cytochrome
      into His-His, typical of b-type cytochromes. The mutant protein was expressed
      heterologously in Escherichia coli at levels 3-fold higher than in Pseudomonas
      and purified to homogeneity. The mutant retained low-spin visible spectral
      characteristics, indicating that the strong field ligand His 61 was coordinated
      to the iron. The physiochemical properties of the mutant were measured and
      compared to the wild-type properties. These included visible spectra, ligand
      binding reactions, stability to temperature and chemical denaturant, oxidation
      reduction potentials, and electron-transfer kinetics to the physiological nitrite
      reductase of Pseudomonas. Despite a change in potential from the normal 260 mV to
      55 mV, the mutant retained many of the properties of the c-551 family.

PMID- 10913315
TI  - Porphobilinogen synthase from pea: expression from an artificial gene, kinetic
      characterization, and novel implications for subunit interactions.
AB  - Porphobilinogen synthase (PBGS) is present in all organisms that synthesize
      tetrapyrroles such as heme, chlorophyll, and vitamin B(12). The homooctameric
      metalloenzyme catalyzes the condensation of two 5-aminolevulinic acid molecules
      to form the tetrapyrrole precursor porphobilinogen. An artificial gene encoding
      PBGS of pea (Pisum sativum L.) was designed to overcome previous problems during
      bacterial expression caused by suboptimal codon usage and was constructed by
      recursive polymerase chain reaction from synthetic oligonucleotides. The
      recombinant 330 residue enzyme without a putative chloroplast transit peptide was
      expressed in Escherichia coli and purified in 100-mg quantities. The specific
      activity is protein concentration dependent, which indicates that a maximally
      active octamer can dissociate into less active smaller units. The enzyme is most
      active at slightly alkaline pH; it shows two pK(a) values of 7.4 and 9.7. Atomic
      absorption spectroscopy shows maximal binding of three Mg(II) per subunit;
      kinetic data support two functionally distinct types of Mg(II) and the third
      appears to be nonphysiologic and inhibitory. Analysis of the protein
      concentration dependence of the specific activity suggests that the minimal
      functional unit is a tetramer. A model of octameric pea PBGS was built to predict
      the location of intermolecular disulfide linkages that were revealed by
      nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. As
      verified by site-specific mutagenesis, disulfide linkages can form between four
      cysteines per octamer, each located five amino acids from the C-terminus. These
      data are consistent with the protein undergoing conformational changes and the
      idea that whole-body motion can occur between subunits.

PMID- 10913316
TI  - Class I MHC is stabilized against thermal denaturation by physiological
      concentrations of NaCl.
AB  - Class I MHC molecules are ternary complexes composed of an allotype specific
      heavy chain, a noncovalently associated protein beta(2)-microglobulin (beta(2)m),
      and a peptide. The complexes are assembled in the endoplasmic reticulum by a
      complex series of chaperones and peptide-loading mechanisms. In the absence of
      beta(2)m or peptide, very little class I heavy chain is transported to the
      surface of the cell. Complexes that do not contain all three parts of the protein
      are not made productively in vivo and not at all in vitro. The ability of the
      complex to withstand thermal denaturation in vitro has been shown to be related
      to the binding affinity of the peptide. Paradoxically, some low-affinity peptide
      complexes denature at or below human basal body temperatures in vitro but are
      effective biological agents in vivo. Here we show that these complexes are
      stabilized against thermal denaturation by physiological cosolvents and maximally
      stabilized by 150 mM NaCl. While the degree of stabilization by 150 mM NaCl is
      greatest for low-affinity peptide/MHC complexes, the mechanism of stabilization
      is independent of peptide sequence. This effect is hypothesized to occur by
      multiple mechanisms including increasing the affinity of beta(2)m for the complex
      and charge screening.

PMID- 10913317
TI  - Role of phosphorylation in the conformation of tau peptides implicated in
      Alzheimer's disease.
AB  - A series of peptides corresponding to isolated regions of Tau (tau) protein have
      been synthesized and their conformations determined by (1)H NMR spectroscopy.
      Immunodominant peptides corresponding to tau(224-240) and a bisphosphorylated
      derivative in which a single Thr and a single Ser are phosphorylated at positions
      231 and 235 respectively, and which are recognized by an Alzheimer's disease
      specific monoclonal antibody, were the main focus of the study. The
      nonphosphorylated peptide adopts essentially a random coil conformation in
      aqueous solution, but becomes slightly more ordered into beta-type structure as
      the hydrophobicity of the solvent is increased by adding up to 50%
      trifluoroethanol (TFE). Similar trends are observed for the bisphosphorylated
      peptide, with a somewhat stronger tendency to form an extended structure. There
      is tentative NMR evidence for a small population of species containing a turn at
      residues 229-231 in the phosphorylated peptide, and this is strongly supported by
      CD spectroscopy. A proposal that the selection of a bioactive conformation from a
      disordered solution ensemble may be an important step (in either tubulin binding
      or in the formation of PHF) is supported by kinetic data on Pro isomerization. A
      recent study showed that Thr231 phosphorylation affected the rate of prolyl
      isomerization and abolished tubulin binding. This binding was restored by the
      action of the prolyl isomerase Pin1. In the current study, we find evidence for
      the existence of both trans and cis forms of tau peptides in solution but no
      difference in the equilibrium distribution of cis-trans isomers upon
      phosphorylation. Increasing hydrophobicity decreases the prevalence of cis forms
      and increases the major trans conformation of each of the prolines present in
      these molecules. We also synthesized mutant peptides containing Tyr substitutions
      preceding the Pro residues and found that phosphorylation of Tyr appears to have
      an effect on the equilibrium ratio of cis-trans isomerization and decreases the
      cis content.

PMID- 10913318
TI  - Characterization of an alkaline transition intermediate stabilized in the
      Phe82Trp variant of yeast iso-1-cytochrome c.
AB  - In general, mutation of the phylogenetically conserved residue Phe82 in yeast iso
      1-cytochrome c destabilizes the native conformation of the protein by
      facilitating the ligand exchange reactions that are associated with the alkaline
      conformational transitions of the ferricytochrome. Of the Phe82 variants surveyed
      thus far, Phe82Trp is unique in that it adopts a thermodynamically stable, high
      spin conformation at mildly alkaline pH. This species exhibits spectroscopic
      features that can only be detected transiently in other ferricytochromes c within
      the first 100 ms immediately after a pH-jump from neutrality to pH >10.
      Spectroscopic characterization of this high-spin reaction intermediate suggests
      that in addition to an obligatory pentacoordinate heme iron, a group within the
      heme pocket coordinates the heme iron but is then replaced either by Met80, to
      revert to the native conformation, or by Lys73 or Lys79, to yield one of the
      conventional alkaline conformers. Evidence is presented to suggest that this
      group is either a hydroxide ion or Tyr67 rather than a loosely bound Met80.

PMID- 10913319
TI  - Statistical parametric mapping of regional glucose metabolism in mesial temporal
      lobe epilepsy.
AB  - We investigated statistical parametric mapping (SPM) use for positron emission
      tomography (PET) with [(18)F]fluorodeoxyglucose (FDG) data analysis in mesial
      temporal lobe epilepsy. The study involved 14 patients with temporal lobe
      epilepsy ultimately treated by anterior temporal lobectomy. Surgical outcome in
      terms of seizure control was favorable in 12 patients. Two different SPM
      approaches were designed to analyze each FDG-PET scan: a direct comparison with a
      control group (n = 27) and a search for significant interhemispheric asymmetry
      considering the asymmetry existing in the control group. Statistical inference
      was performed, first, without correction for multiple comparisons (making the
      hypothesis of temporal hypometabolism) and, second, after correction for multiple
      comparisons. Search for temporal interhemispheric asymmetry under the hypothesis
      of temporal hypometabolism was the most reliable SPM approach: hypometabolism was
      identified on the side chosen for resection in most cases (sensitivity, 71%;
      specificity, 100%) and was predictive of favorable postsurgical outcome in 90% of
      the patients. There was no false-positive result within the control group using
      this approach. After correction for multiple comparisons, SPM also identified in
      some patients temporal hypermetabolic areas as well as extratemporal cortical and
      subcortical hypometabolic areas on the side of resection but also on the
      contralateral side. In a further step, SPM was used for a group analysis of
      patients with favorable outcome after reversing scans when needed to set an
      identical lateralization in all patients. This analysis identified multiple
      ipsilateral temporal and extratemporal hypometabolic regions; when temporal
      metabolic changes were specifically assessed, the contralateral mesiotemporal
      region was found hypermetabolic, possibly as a manifestation of compensatory
      mechanisms in the presence of a unilateral epileptogenic lesion.

PMID- 10913320
TI  - Movement-related electroencephalographic reactivity in Alzheimer disease.
AB  - Event-related desynchronization/synchronization (ERD/ERS) of alpha and beta
      electroencephalographic (EEG) rhythms was investigated in normal subjects and
      mild Alzheimer Disease patients (AD), performing unilateral right finger
      movements (about 10 s intermovement interval). Electroencephalographic data were
      sampled based on 10-20 system electrode montage. Surface Laplacian estimate of
      the potential reduced the head-volume conductor effects and annulled electrode
      reference variations. Results showed that EEG reactivity (i.e., ERD/ERS) of
      modeled contralateral rolandic cortex and motor performance were preserved in
      mild to moderate AD. In contrast, modeled activity (i.e., ERD/ERS) of
      frontolateral, centromedial, and ipsilateral rolandic areas was abnormal.
      Furthermore, interrelatedness of cortical response and movement timing was
      abnormal in AD patients. These results would support the working hypothesis that
      mild to moderate AD is a global brain network disease, including processing of
      sensorimotor information (despite no overt movement disorder). Further
      investigations will ascertain the clinical relevance of these results.

PMID- 10913321
TI  - Functional differentiation in the human auditory and language areas revealed by a
      dichotic listening task.
AB  - The human auditory cortex plays a special role in speech recognition. It is
      therefore necessary to clarify the functional roles of individual auditory areas.
      We applied functional magnetic resonance imaging (fMRI) to examine cortical
      responses to speech sounds, which were presented under the dichotic and diotic
      (binaural) listening conditions. We found two different response patterns in
      multiple auditory areas and language-related areas. In the auditory cortex, the
      medial portion of the secondary auditory area (A2), as well as a part of the
      planum temporale (PT) and the superior temporal gyrus and sulcus (ST), showed
      greater responses under the dichotic condition than under the diotic condition.
      This dichotic selectivity may reflect acoustic differences and attention-related
      factors such as spatial attention and selective attention to targets. In
      contrast, other parts of the auditory cortex showed comparable responses to the
      dichotic and diotic conditions. We found similar functional differentiation in
      the inferior frontal (IF) cortex. These results suggest that multiple auditory
      and language areas may play a pivotal role in integrating the functional
      differentiation for speech recognition.

PMID- 10913322
TI  - Multistart algorithms for MEG empirical data analysis reliably characterize
      locations and time courses of multiple sources.
AB  - We applied our newly developed Multistart algorithm (M. Huang et al., 1998,
      Electroencephalogr. Clin. Neurophysiol. 108, 32-44) to high signal-to-noise ratio
      (SNR) somatosensory responses and low SNR visual data to demonstrate the
      reliability of this analysis tool for determining source locations and time
      courses of empirical multisource neuromagnetic data. This algorithm performs a
      downhill simplex search hundreds to thousands of times with multiple, randomly
      selected initial starting parameters from within the head volume, in order to
      avoid problems of local minima. Two subjects participated in two studies: (1)
      somatosensory (left and right median nerves were stimulated using a square wave
      pulse of 0.2 ms duration) and (2) visual (small black and white bull's-eye
      patterns were presented to central and peripheral locations in four quadrants of
      the visual field). One subject participated in both of the studies mentioned
      above and in a third study (i.e., simultaneous somatosensory/visual stimulation).
      The best-fitting solutions were tightly clustered in high SNR somatosensory data
      and all dominant regions of activity could be identified in some instances by
      using a single model order (e.g., six dipoles) applied to a single interval of
      time (e.g., 15-250 ms) that captured the entire somatosensory response. In low
      SNR visual data, solutions were obtained from several different model orders and
      time intervals in order to capture the dominant activity across the entire visual
      response (e.g. , 60-300 ms). Our results demonstrate that Multistart MEG analysis
      procedures can localize multiple regions of activity and characterize their time
      courses in a reliable fashion. Sources for visual data were determined by
      comparing results across several different models, each of which was based on
      hundreds to thousands of different fits to the data.

PMID- 10913323
TI  - Nonlinear regression of functional MRI data: an item recognition task study.
AB  - A classical item-recognition task was used to examine human verbal working memory
      in an event-related functional MRI (fMRI) study. A highly flexible experimental
      design incorporated a broad variation of memory load and delay time. This design
      allows for only three or four repetitions per stimulus condition. In a first
      step, linear regression analysis was applied to locate functional activation in
      the fMRI data. As a second step, the time course of the hemodynamic response (HR)
      was analyzed using nonlinear regression, which served to quantify the dependency
      between HR shape properties and stimulation conditions in several regions-of
      interest. On the basis of this study, a closer description of the frontoparietal
      network involved in verbal working memory was possible.

PMID- 10913324
TI  - Regularization of diffusion-based direction maps for the tracking of brain white
      matter fascicles.
AB  - Magnetic resonance diffusion tensor imaging (DTI) provides information about
      fiber local directions in brain white matter. This paper addresses inference of
      the connectivity induced by fascicles made up of numerous fibers from such
      diffusion data. The usual fascicle tracking idea, which consists of following
      locally the direction of highest diffusion, is prone to erroneous forks because
      of problems induced by fiber crossing. In this paper, this difficulty is partly
      overcomed by the use of a priori knowledge of the low curvature of most of the
      fascicles. This knowledge is embedded in a model of the bending energy of a
      spaghetti plate representation of the white matter used to compute a regularized
      fascicle direction map. A new tracking algorithm is then proposed to highlight
      putative fascicle trajectories from this direction map. This algorithm takes into
      account potential fan shaped junctions between fascicles. A study of the tracking
      behavior according to the influence given to the a priori knowledge is proposed
      and concrete tracking results obtained with in vivo human brain data are
      illustrated. These results include putative trajectories of some pyramidal,
      commissural, and various association fibers.

PMID- 10913325
TI  - To smooth or not to smooth? Bias and efficiency in fMRI time-series analysis.
AB  - This paper concerns temporal filtering in fMRI time-series analysis. Whitening
      serially correlated data is the most efficient approach to parameter estimation.
      However, if there is a discrepancy between the assumed and the actual
      correlations, whitening can render the analysis exquisitely sensitive to bias
      when estimating the standard error of the ensuing parameter estimates. This bias,
      although not expressed in terms of the estimated responses, has profound effects
      on any statistic used for inference. The special constraints of fMRI analysis
      ensure that there will always be a misspecification of the assumed serial
      correlations. One resolution of this problem is to filter the data to minimize
      bias, while maintaining a reasonable degree of efficiency. In this paper we
      present expressions for efficiency (of parameter estimation) and bias (in
      estimating standard error) in terms of assumed and actual correlation structures
      in the context of the general linear model. We show that: (i) Whitening
      strategies can result in profound bias and are therefore probably precluded in
      parametric fMRI data analyses. (ii) Band-pass filtering, and implicitly
      smoothing, has an important role in protecting against inferential bias.

PMID- 10913326
TI  - In vivo magnetic resonance imaging of embryonic neural grafts in a rat model of
      striatonigral degeneration (multiple system atrophy).
AB  - The effects of embryonic neural transplantation in experimental models of
      neurodegenerative disorders are commonly assessed by behavioral tests and
      postmortem neurochemical or anatomical analysis. The purpose of the present study
      was to evaluate embryonic neuronal grafts in a novel rat model of multiple system
      atrophy (MSA) with the help of in vivo magnetic resonance imaging (MRI) and to
      correlate imaging with histological parameters. Striatonigral double lesions were
      created in male Wistar rats by unilateral intrastriatal injection of 3
      nitropropionic acid (3-NP). Seven weeks following lesion surgery animals were
      divided into four transplantation groups receiving either pure mesencephalic,
      pure striatal, mesencephalic-striatal cografts, or sham grafts. In vivo
      structural imaging was performed 21 weeks after transplantation using a whole
      body 1.5 Tesla MR scanner. The imaging protocol comprised T2-weighted TSE and T1
      weighted TIR sequences. Immunohistochemistry using DARPP-32 as striatal marker
      and tyrosinhydroxylase as marker for nigral neurons was performed for correlation
      analysis of imaging and histological parameters. The sensitivity of graft
      detection by in vivo MRI was 100%. The graft tissue was clearly demarcated from
      the remaining striatal tissue in both T2- and T1-weighted sequences.
      Morphometrically, cross-sectional areas of the grafts and spared intact striatum
      as defined by immunohistochemistry correlated significantly with measurements
      obtained by in vivo MRI. In conclusion, we were able to evaluate in vivo both
      lesion-induced damage and graft size in a 3-NP rat model of MSA using a
      conventional whole body 1.5 Tesla MRI scanner. Additionally, we obtained an
      excellent correlation between MRI and histological measurements.

PMID- 10913327
TI  - Selection of an adaptive test statistic for use with multiple comparison analyses
      of neuroimaging data.
AB  - Statistical analysis of neuroimages is commonly approached with intergroup
      comparisons made by repeated application of univariate or multivariate tests
      performed on the set of the regions of interest sampled in the acquired images.
      The use of such large numbers of tests requires application of techniques for
      correction for multiple comparisons. Standard multiple comparison adjustments
      (such as the Bonferroni) may be overly conservative when data are correlated
      and/or not normally distributed. Resampling-based step-down procedures that
      successfully account for unknown correlation structures in the data have recently
      been introduced. We combined resampling step-down procedures with the Minimum
      Variance Adaptive method, which allows selection of an optimal test statistic
      from a predefined class of statistics for the data under analysis. As shown in
      simulation studies and analysis of autoradiographic data, the combined technique
      exhibits a significant increase in statistical power, even for small sample sizes
      (n = 8, 9, 10).

PMID- 10913328
TI  - A method for removing imaging artifact from continuous EEG recorded during
      functional MRI.
AB  - Combined EEG/fMRI recording has been used to localize the generators of EEG
      events and to identify subject state in cognitive studies and is of increasing
      interest. However, the large EEG artifacts induced during fMRI have precluded
      simultaneous EEG and fMRI recording, restricting study design. Removing this
      artifact is difficult, as it normally exceeds EEG significantly and contains
      components in the EEG frequency range. We have developed a recording system and
      an artifact reduction method that reduce this artifact effectively. The recording
      system has large dynamic range to capture both low-amplitude EEG and large
      imaging artifact without distortion (resolution 2 microV, range 33.3 mV), 5-kHz
      sampling, and low-pass filtering prior to the main gain stage. Imaging artifact
      is reduced by subtracting an averaged artifact waveform, followed by adaptive
      noise cancellation to reduce any residual artifact. This method was validated in
      recordings from five subjects using periodic and continuous fMRI sequences.
      Spectral analysis revealed differences of only 10 to 18% between EEG recorded in
      the scanner without fMRI and the corrected EEG. Ninety-nine percent of spike
      waves (median 74 microV) added to the recordings were identified in the corrected
      EEG compared to 12% in the uncorrected EEG. The median noise after artifact
      reduction was 8 microV. All these measures indicate that most of the artifact was
      removed, with minimal EEG distortion. Using this recording system and artifact
      reduction method, we have demonstrated that simultaneous EEG/fMRI studies are for
      the first time possible, extending the scope of EEG/fMRI studies considerably.

PMID- 10913329
TI  - Correlator beware: correlation has limited selectivity for fMRI data analysis.
AB  - Groups of time-courses created from fMRI data by the frequently used correlation
      analysis are often highly heterogeneous. This heterogeneity is due to the limited
      selectivity of correlation when trying to match brain time-courses to an
      externally imposed activation paradigm. Thus, this process unnecessarily
      generates many type I errors (false positives). Furthermore, as a consequence of
      the heterogeneity, time-courses identified and grouped by correlation may in fact
      describe different activations. After demonstrating this inadequacy, we give one
      particular approach to partition such a heterogeneous group into internally more
      homogeneous subgroups, using Kendall's coefficient of concordance W, and show its
      applicability and application to both simulated and in vivo data. Such group
      partition and "purification" will help subsequent inferential methods to deal
      more efficiently with false positives.

PMID- 10913330
TI  - Genomic characterization and embryonic expression of the mouse Bigh3 (Tgfbi)
      gene.
AB  - Mutations in human BIGH3 (TGFB1), a gene identified after treatment of an
      adenocarcinoma cell line with TGF-beta, have been observed in patients with
      granular Groenouw type I, Reis-Bucklers, Thiel-Behnke, Avellino, and Lattice type
      I and IIIa, six autosomal dominant corneal dystrophies linked to chromosome 5q.
      In order to gain insight into the physiological role of this gene, we
      characterized the genomic structure of the mouse Bigh3 and its expression in
      murine embryos. The gene spans 30 kb on mouse chromosome 13 and has 17 exons.
      Embryonic expression of Bigh3 is observed in the mesenchyme of the first and
      second branchial arches as early as dpc 11.5 and is particularly strong in the
      mesenchyme of numerous tissues throughout all the development stages. In fetal
      eye, the expression is first seen at 11.5 dpc in the mesenchyme surrounding the
      optic stalk, extends toward the sclera and choroid by 14.3 dpc and reaches the
      cornea by 17.5 dpc. Because the physiological role of BIGH3/Bigh3 is still
      largely unknown, embryonic expression in organs like heart, vessels, and
      intestine may help to identify new functions which could be searched for in
      patients and in knock-out animal models. The characterization of the murine
      structure is a prerequisite for the making of such models.

PMID- 10913331
TI  - Mitochondrial expression of a short dystrophin-like product with molecular weight
      of 71 kDa.
AB  - In the brain, Dp71 is the most abundant protein product of the DMD gene and by
      alternative splicing of exon 78 two isoforms can be expressed, Dp71d and Dp71f.
      To explore the subcellular distribution of these Dp71 isoforms, specific
      monoclonal antibodies were used. Dp71d (with exon 78) was found in microsomes,
      while Dp71f (without exon 78) was detected in mitochondria. To determine the
      alterations which the absence of dystrophin proteins induces, we compared the
      expression of Dp71d in microsomes and Dp71f in mitochondria from mdx and mdx(3CV)
      mice. Dp71d in microsomes of mdx was similar to that of wild-type mice and, as
      expected, in mdx(3CV) this protein was undetectable. However, in mitochondria
      from mdx(3CV), Dp71f was overexpressed in comparison to mitochondria from mdx
      mice. Because in mdx(3CV) mice all the dystrophin proteins are mutated or
      diminished, we concluded that the protein detected in mitochondria is not a Dp71f
      but a novel product named Dp71f-like protein.

PMID- 10913332
TI  - Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in
      mouse calvaria.
AB  - The stimulators of bone resorption, prostaglandin E(2) (PGE(2)) and 1,25
      dihydroxyvitamin D(3) (1,25D(3)), act through osteoblast-like cells to activate
      osteoclasts. One candidate for the intermediary produced by osteoblasts that
      subsequently stimulates the osteoclast is osteoprotegerin ligand (OPGL). OPGL has
      been shown to stimulate osteoclast differentiation and activation. The aim of the
      work reported here was to determine if soluble recombinant extracellular domain
      of human OPGL would bring about the change in osteoclast adhesion from the
      periosteum of mouse calvaria to the adjacent bone surface that occurs with the
      above-mentioned stimulators of resorption. This change in adherence or
      translocation of osteoclasts onto the bone surface required the expression and
      functioning of the integrin subunit, beta 3. We show that this soluble OPGL, like
      PGE(2) and 1,25D(3), stimulated the release of osteoclasts from the periosteum
      and their adherence to the bone surface accompanied by an increase in staining
      for immunolocalized integrin subunit beta 3. Recombinant human osteoprotegerin
      (OPG), which binds strongly to OPGL, inhibited this translocation of osteoclasts
      that occurred with PGE(2) and 1,25D(3), leaving integrin beta-3-negative
      osteoclasts on the periosteum. PGE(2) and 1,25D(3) increased the expression of
      messenger RNA for OPGL compared with indomethacin-treated controls after 6 h
      exposure. Evidence is presented that the change in the adhesion of osteoclasts
      from the periosteum to the bone surface, resulting in osteoclast activation, is
      mediated by OPGL.

PMID- 10913333
TI  - Diversity of N-acetylglucosamine-6-O-sulfotransferases: molecular cloning of a
      novel enzyme with different distribution and specificities.
AB  - N-Acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) transfers sulfate to the C-6
      position of non-reducing N-acetylglucosamine (GlcNAc) residues. We cloned human
      and mouse cDNAs encoding a novel GlcNAc6ST, designated as GlcNAc6ST-4, which
      showed sequence identities of 26 to 41% to other GlcNAc6STs. Human organs with
      strong expression of the enzyme mRNA were the heart, spleen, and ovary, while in
      the mouse strong expression was detected in the kidney. The enzyme expressed in
      CHO cells preferentially acted on mannose-linked GlcNAc, while a core 2 mucin
      type oligosaccharide and an N-acetyllactosamine oligomer also served as
      acceptors. The distribution and the specificity of GlcNAc6ST are different from
      those of GlcNAc6STs identified previously.

PMID- 10913334
TI  - Homozygosity for the R1268Q mutation in MRP6, the pseudoxanthoma elasticum gene,
      is not disease-causing.
AB  - Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder of connective
      tissue, characterized by progressive calcification of the elastic fibers in the
      eye, the skin, and the cardiovascular system, resulting in decreased vision, skin
      lesions, and life-threatening vascular disease, with highly variable phenotypic
      expression. The PXE locus has been mapped to chromosome 16p13.1, and was recently
      further refined to a 500 kb-region, containing two pseudogenes and four candidate
      genes. In a comprehensive mutational screening, we were able to exclude the
      responsibility of pM5, UNK, and MRP1 genes, candidate on the basis of their
      genetic localization. Conversely, we have found pathogenetic mutations in the
      MRP6 gene, in patients affected with PXE, indicating that human MRP6, which
      encodes a 1503 amino-acids membrane protein, member of the human ATP binding
      cassette (ABC) transporters superfamily, is the gene responsible for PXE. In one
      large PXE pedigree for which we had identified a nonsense mutation (R1141X), we
      came across a G to A transition at position 3803 of the MRP6 cDNA sequence
      (R1268Q). Astonishingly, this latter variant was found at the homozygous state in
      the proband's unaffected husband. We investigated the R1268Q mutation, and found
      the Q1268 allele at a relatively high frequency (0.19) in a Caucasian control
      population (n = 62 subjects). Genotype frequencies were in Hardy-Weinberg
      equilibrium, and three healthy volunteers were homozygous for the Q1268 allele.
      These data indicate that the R1268Q variant in the MRP6 gene does not cause PXE
      per se. Further studies will elucidate if it may play a role when found in
      compound heterozygotes.

PMID- 10913335
TI  - Genomic structure and expression of human KCNJ9 (Kir3.3/GIRK3).
AB  - The human KCNJ9 (Kir 3.3, GIRK3) is a member of the G-protein-activated inwardly
      rectifying potassium (GIRK) channel family. Here we describe the genomic
      organization of the KCNJ9 locus on chromosome 1q21-23 as a candidate gene for
      Type II diabetes mellitus in the Pima Indian population. The gene spans
      approximately 7.6 kb and contains one noncoding and two coding exons separated by
      approximately 2.2 and approximately 2.6 kb introns, respectively. We identified
      14 single nucleotide polymorphisms (SNPs), including one that predicts a
      Val366Ala substitution, and an 8 base-pair (bp) insertion/deletion. Our
      expression studies revealed the presence of the transcript in various human
      tissues including pancreas, and two major insulin-responsive tissues: fat and
      skeletal muscle. The characterization of the KCNJ9 gene should facilitate further
      studies on the function of the KCNJ9 protein and allow evaluation of the
      potential role of the locus in Type II diabetes.

PMID- 10913336
TI  - Orexins suppress catecholamine synthesis and secretion in cultured PC12 cells.
AB  - New orexigenic peptides called orexin-A and -B have recently been described in
      neurons of the lateral hypothalamus and perifornical area. No orexins have been
      found in adipose tissues or visceral organs, including the adrenal gland.
      However, expression of the orexin-receptor 2 (OX2R) in the rat adrenal gland has
      been reported. To test the effects of orexins on peripheral organs, we
      investigated their effects on catecholamine synthesis and secretion in the rat
      pheochromocytoma cell line PC12. Orexin-A and -B (100 nM) significantly reduced
      basal and PACAP-induced tyrosine hydroxylase (TH) (the rate-limiting enzyme in
      the biosynthesis of catecholamines) mRNA levels. Orexin-A and -B (100 nM) also
      significantly inhibited the PACAP-induced increase in the cAMP level, suggesting
      that the suppressive effect on TH mRNA is mediated, at least in part, by the
      cAMP/protein kinase A pathway. Furthermore, orexin-A and -B (100 nM)
      significantly suppressed basal and PACAP-induced dopamine secretion from PC12
      cells. Next, we examined whether orexin receptors (OX1R, OX2R) were present in
      the rat adrenal gland and PC12 cells. In the adrenal glands, OX2R was as strongly
      expressed as in the hypothalamus, but OX1R was not detected. On the other hand,
      neither OX1R nor OX2R was expressed in PC12 cells. However, binding assays showed
      equal binding of orexin-A and -B to PC12 cells, suggesting the existence in these
      cells of some receptors for orexins. These results indicate that orexins suppress
      catecholamine release and synthesis, and that the inhibitory effect is mediated
      by the cAMP/protein kinase A pathway.

PMID- 10913337
TI  - The molecular characterization and tissue distribution of the human cysteinyl
      leukotriene CysLT(2) receptor.
AB  - Cysteinyl leukotrienes (CysLTs), slow-reacting substances of anaphylaxis, are
      lipid mediators known to possess potent proinflammatory action. Pharmacological
      studies using CysLTs indicate that at least two classes of G protein-coupled
      receptors (GPCRs), named CysLT(1) and CysLT(2), exist; the former is sensitive
      and the latter is resistant to the CysLT(1) antagonists currently used to treat
      asthma. Although the CysLT(1) receptor gene has been recently cloned, the
      molecular identity of the CysLT(2) receptor has remained elusive. Here we show
      that the pharmacological profile of an orphan GPCR (PSEC0146) is consistent with
      that of the CysLT(2) receptor. In human embryonic kidney 293 cells that express
      the PSEC0146 cDNA, leukotriene C(4) (LTC(4)) and leukotriene D(4) (LTD(4)) induce
      equal increases in intracellular calcium mobilization; these increases are not
      affected by CysLT(1) antagonists. Additionally, [(3)H]LTC(4) specifically binds
      to membranes from COS-1 cells transiently transfected with PSEC0146. Large
      amounts of the PSEC0146 mRNA are found in human heart, placenta, spleen, and
      peripheral blood leukocytes but not in the lung and the trachea. Pharmacological
      feature and expression studies will eventually lead to a better understanding of
      the classification of CysLT receptors, possibly leading to a reconsideration of
      the pathological and physiological role of CysLTs.

PMID- 10913339
TI  - Jumonji is a nuclear protein that participates in the negative regulation of cell
      growth.
AB  - The jumonji (jmj) gene, obtained by a gene trap strategy, is essential for mouse
      embryogenesis and is suggested to play important roles in cell growth during
      development. The amino acid sequence of the Jmj protein includes a nuclear
      localization signal and a DNA binding motif called the AT-rich interaction domain
      (ARID). To investigate the biological functions of the Jmj protein, we prepared
      specific antibodies. Using these antibodies, we showed that the Jmj protein is a
      160-kDa protein and localizes in the nuclei of COS-7 cells transfected with jmj
      cDNA and megakaryocytes from fetal liver which show strong endogenous expression
      of the jmj gene. Moreover, overexpression of the Jmj protein in COS-7 and NIH3T3
      cells remarkably reduced cell proliferation compared with control cells
      transfected with vector alone. These results show that the Jmj protein acts in
      cell nuclei and participates in the negative regulation of cell proliferation
      signaling.

PMID- 10913338
TI  - Involvement of the glucose-regulated protein 94 (Dd-GRP94) in starvation response
      of Dictyostelium discoideum cells.
AB  - Upon deprivation of nutrients, Dictyostelium discoideum Ax-2 cells arrest
      proliferation and initiate a metamorphosed developmental program including
      induction of altered gene expressions which are necessary for differentiation. In
      Ax-2 cells, we found out a member of Hsp90 family usually contained in the
      endoplasmic reticulum (ER), Dd-GRP94 (Dictyostelium discoideum glucose-regulated
      protein 94). In general, GRP94 are induced either by glucose-depletion or by
      depletion of Ca(2+) in intracellular Ca(2+) stores. Unexpectedly, however, the
      expression of Dd-grp94 was greatly reduced within 60 min of starvation. Dd-grp94
      overexpressing cells (GRP94(OE) cells) collected without forming distinct
      aggregation streams, and never formed normal fruiting bodies. Also, prespore
      differentiation as well as maturation into spores and stalk cells were
      particularly impaired in the GRP94(OE) cells. Thus Dd-GRP94 seems to be crucial
      in late differentiation as well as in starvation response.

PMID- 10913340
TI  - Molecular cloning and characterization of human FGF-20 on chromosome 8p21.3-p22.
AB  - The fibroblast growth factors (FGFs) play important roles in morphogenesis,
      angiogenesis, tissue remodeling, and carcinogenesis. Human FGF-20 has been cloned
      and characterized in this study. FGF-20 encodes a 211-amino-acid polypeptide with
      the FGF-core domain. A strong hydrophobic region was found in the FGF-core domain
      of FGF-20; however, no typical N-terminal signal sequence was found in FGF-20,
      just as in FGF-9 and FGF-16. Total amino acid identities are as follows: FGF-20
      vs FGF-9, 71.6%; FGF-20 vs FGF-16, 66.2%; FGF-9 vs FGF-16, 72.4%. Phylogenic
      analysis indicated that FGF-20, FGF-9, and FGF-16 constitute a subfamily among
      the FGF family. FGF-20 mRNA of 2.4 kb in size was detected in colon cancer cell
      line SW480 by Northern blot analysis. Lower levels of FGF-20 mRNA were detected
      in human fetal tissues and primary cancers by cDNA-PCR. The nucleotide sequence
      of FGF-20 cDNA is split into three parts in the human genome sequence of the
      chromosome 8p21.3-p22 region (Accession No. AB020858). These results indicate
      that the FGF-20 gene, located on human chromosome 8p21.3-p22, consists of three
      exons. Compared with the nucleotide sequence of FGF-20 cDNA determined in this
      study, one nucleotide deletion and one nucleotide substitution in the putative
      coding region were identified in human genome sequence AB020858.

PMID- 10913341
TI  - Electrophysiologic characteristics of the Ca-permeable channels, ECaC and CaT, in
      the kidney.
AB  - To investigate the molecular mechanism of Ca transport in the kidney, we have
      isolated Ca-permeable channels, rECaC (rat ECaC) and mCaT (mouse CaT1), from
      rodent kidney, which are recently reported as Ca-transporting proteins. RT-PCR
      suggested the presence of CaT1 in medullary tubules. It showed 67% homology with
      rECaC constructing a family. Whole cellular currents in Chinese hamster ovary
      (CHO) cells were measured by patch clamp. Expression of both proteins exhibited a
      similar large cation current, a high permeability to Ca, a time-dependent rapid
      inactivation, and a "run-down." When the pipet contained EGTA, the inactivation
      and the run-down did not occur. Addition of db-cAMP activated and following rp
      cAMPS recovered the mCaT-induced current significantly, whereas no influence was
      observed in the rECaC-induced one. We conclude that ECaC and CaT are a molecular
      family of ion channel with similar characteristics, contributing Ca transport in
      the kidney.

PMID- 10913342
TI  - cDNA Cloning and mRNA analysis of PGC-1 in epitrochlearis muscle in swimming
      exercised rats.
AB  - Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1), a cold
      inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis
      and respiration in muscle cells. In the present study, we first cloned a rat PGC
      1 gene from a brown adipose tissue cDNA library which encodes a predicted 796
      amino-acid protein and exhibits respectively 98% and 95% identity with the mouse
      and human homologues. Next, we examined the effect of swimming exercise training
      on the level of expression of the PGC-1 gene in rat epitrochlearis (Epi) muscle.
      PGC-1 mRNA level in Epi muscle in rats that swam 2 h a day for 3 and 7 days
      increased dramatically by 154% and 163%, respectively, compared to the non
      exercised control group. PGC-1 mRNA up-regulation was not observed in an
      immersion group treated at 35 degrees C during the training program but without
      swimming exercise. These results demonstrate that expression of the PGC-1 gene in
      Epi muscle is induced not only by cold exposure but also by prolonged low
      intensity physical exercise.

PMID- 10913343
TI  - Sucrose-diet feeding induces gene expression of heat shock protein in rat brain
      under stress.
AB  - Stress-induced hyperphagia is enhanced in the presence of sweets, particularly
      sucrose, which may act to attenuate stress. Recently, it was also reported that
      heat shock protein (HSP) may be involved in the defense against stress. To
      explore whether sucrose alters gene expression of HSP under stress, we determined
      the HSP mRNA levels in the hypothalamus, cerebellum, and cerebral cortex after
      restraint stress in sucrose-diet-fed rats. Competitive RT-PCR revealed that gene
      expressions of HSP27 in the cerebral cortex and cerebellum and of HSP70 in the
      cerebral cortex, hypothalamus, and cerebellum were induced by restraint stress
      under a sucrose-diet-fed condition. However, restraint stress by itself or
      sucrose diet alone did not induce expression of HSP27 or HSP70 mRNA in any of the
      three anatomical parts. It is suggested that sucrose facilitates the gene
      expression of HSP27 and HSP70 in brain after restraint stress, which may
      attenuate stress.

PMID- 10913344
TI  - NMR studies on novel antitumor drug candidates, deoxoartemisinin and
      carboxypropyldeoxoartemisinin.
AB  - Artemisinin and its derivatives, which have been known as antimalarial drugs,
      have also demonstrated their cytotoxicity against tumor cells. It has been
      proposed that antitumor activity depends on the lipophilicity of functional group
      on artemisinin derivatives. Solution structures of two artemisinin derivatives as
      antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin,
      were determined by NMR spectroscopy to elucidate structure-activity relationship.
      According to biological assay, antitumor efficiencies are not dependent upon
      lipophilicity. Instead, these compounds demonstrated their distinctive structural
      features of boat/chair conformation and capability to interact with receptors, as
      they have different efficiencies on antitumor activity. Especially, carboxypropyl
      moiety or carbonyl moiety in artemisinin derivatives influences the conformation
      and stability of ring structure. Although the detailed mechanism of antitumor
      activity by artemisinin derivatives has not been addressed, we suggest that
      antitumor activity is not determined only with lipophilicity and that artemisinin
      derivatives have specific target proteins in each type of cancer.

PMID- 10913346
TI  - Cloning and characterization of cDNA encoding a novel human leukotriene B(4)
      receptor.
AB  - By homology screening using BLAST searches of expressed sequence tags (ESTs), we
      have found a previously unidentified cDNA encoding a putative seven-transmembrane
      receptor with highest similarity to the leukotriene B(4) receptor, BLTR. Analysis
      of calcium flow in transfected cells, along with sequence analysis, revealed that
      the EST encoded a functionally inactive protein, lacking the segment
      corresponding to the C-terminal part of the putative receptor protein. The
      missing segment was obtained by PCR amplification of a human leukocyte cDNA
      library and ligated to the truncated EST cDNA. The novel cDNA encodes a full
      length receptor with 39% identity to the previously cloned BLTR. Studies of
      intracellular calcium flow of transfected HeLa cells exposed to various
      leukotrienes showed that also the novel BLTR-like receptor can be activated by
      leukotriene B(4), and it is therefore tentatively named BLTR2.

PMID- 10913345
TI  - Activation of the tumor metastasis suppressor gene, KAI1, by etoposide is
      mediated by p53 and c-Jun genes.
AB  - KAI1 is a metastasis suppressor gene which is capable of inhibiting the processes
      of tumor metastasis without affecting tumorigenicity per se. We found that
      etoposide, a topoisomerase II inhibitor, is able to activate the expression of
      the KAI1 gene in a dose-dependent manner in human prostate cancer cell lines,
      ALVA, DU145, and PC-3 as well as in human lung carcinoma cell A549. The
      activation of the KAI1 gene was mainly mediated by the c-Jun gene in the PC-3 and
      DU145 cell lines, while it was mediated by both p53 and c-Jun genes in the A549
      cell line. These results suggest that the augmentation of the KAI1 gene
      expression is independently controlled by p53 and c-Jun at the transcriptional
      level in the human cancer cell lines. Furthermore, treatment of these cell lines
      with etoposide resulted in significant reduction of cellular invasion measured by
      the Matrigel invasion chamber. Because etoposide has been shown to be effective
      on advanced prostate cancer when used in combination with other regimens, our
      results provide further rationale to use this drug as an antimetastatic agent.

PMID- 10913347
TI  - Genomic organization of the leukotriene B(4) receptor locus of human chromosome
      14.
AB  - The genomic region containing the genes encoding the first leukotriene B(4)
      receptor, BLTR, as well as the recently cloned second leukotriene B(4)-activated
      receptor, BLTR2, was mapped by (a) sequence analysis of a human bacterial
      artificial chromosome (BAC) library containing a 15-kb segment corresponding to
      chromosome 14q11. 2-12 where the BLTR/BLTR2 genes were previously shown to be
      located, together with (b) sequence analysis of 83 expressed sequence tags (ESTs)
      from this region. The BLTR gene includes four different 5' untranslated regions
      (UTRs) and a mutual acceptor site for the exon containing the intronless open
      reading frame. The BLTR2 gene is intronless and overlapped by a 5' UTR splice
      version of BLTR and, on the reverse strand, of the apoptosis-related CIDE-B gene.
      This indicates a complex posttranscriptional gene regulation. Further adding to
      the complexity of the region is evidence of a fourth putative and novel gene,
      most homologous to the rat adenylyl cyclase IV gene.

PMID- 10913348
TI  - Preparation of a monoclonal antibody to N(epsilon)-(Hexanonyl)lysine: application
      to the evaluation of protective effects of flavonoid supplementation against
      exercise-induced oxidative stress in rat skeletal muscle.
AB  - The monoclonal antibody to N(epsilon)-(hexanonyl)lysine (HEL), a novel adduct
      formed by the reaction of linoleic acid hydroperoxide and lysine, has been
      prepared and characterized. The obtained antibody specifically recognized the HEL
      moiety. Using the monoclonal antibody, we evaluated the protective effects of
      feeding eriocitrin, which is one of flavonoids in lemon fruit, on oxidative
      modification induced by exercise in rats. The supplementation of eriocitrin
      significantly suppressed the increase in HEL in the skeletal muscle by exercise.
      The result suggests that the determination of HEL may be a good method for
      evaluation of the protective effect of beneficial food factors against oxidative
      stress.

PMID- 10913349
TI  - Na(+) channel regulation by calmodulin kinase II in rat cerebellar granule cells.
AB  - The effects of specific CaM kinase II inhibitors were investigated on Na(+)
      channels from rat cerebellar granule cells. A maximal effect of KN-62 was
      observed at 20 microM and consisted of an 80% reduction of the peak Na(+) current
      after only a 10-min application. A hyperpolarizing shift of 8 mV in the steady
      state inactivation was also observed. KN-04 (20 microM), an inactive analog, had
      no detectable effect. KN-62 was however inactive on Na(+) currents recorded from
      Chinese hamster ovary cells expressing the type II A alpha subunit. We have also
      analyzed the inhibitory effects of CaM kinase II 296-311 and CaM kinase II 281
      309 peptides. Both peptides (75 microM) induced a maximum peak Na(+) current
      reduction within 30 min. Under similar conditions, a truncated peptide CaM kinase
      II 284-302 was ineffective. These results demonstrate that CaM kinase II acts as
      a modulator of Na(+) channel activity in cerebellar granule cells.

PMID- 10913350
TI  - Microisolated mouse osteoclasts express VIP-1 and PACAP receptors.
AB  - Skeletal tissue contains a network of nerve fibers expressing several
      neuropeptides, including vasoactive intestinal peptide (VIP) and the related
      peptide pituitary adenylate cyclase activating peptide (PACAP). These peptides
      have been demonstrated to regulate osteoclast formation and osteoclast activity.
      Using atomic force microscopy and by analysing changes of the intracellular
      calcium concentrations, we have recently demonstrated that multinucleated rat
      osteoclasts have cell membrane binding sites recognising VIP and PACAP. In the
      present study, we have further studied the expression of VIP receptor subtypes in
      mouse bone marrow cultures and isolated osteoclasts. A micromanipulation
      technique was used to isolate pure populations of osteoclasts formed in PTH
      stimulated mouse bone marrow cultures. By reverse transcriptase polymerase chain
      reaction (RT-PCR), we studied the expression of mRNA for VIP-1, VIP-2, and PACAP
      receptors. The purity of the microisolated osteoclasts was determined by studying
      the expression of specific mRNA associated with the phenotypic trait of
      osteoclasts or osteoblasts/stromal cells. In this study, we show that mouse
      osteoclasts express VIP-1 and PACAP, but not VIP-2, receptor mRNA.

PMID- 10913351
TI  - N-myc down-regulates activin A.
AB  - N-myc oncogene amplification is frequent in human neuroblastoma and predicts poor
      prognosis, but the molecular consequences have remained obscure. We report here
      that enhanced N-myc expression correlates with low or undetectable expression of
      activin A, but not other closely related members of the transforming growth
      factor-beta superfamily. N-myc interacts with the activin A promoter, eventually
      inducing down-regulation of activin A mRNA and protein. This study demonstrates
      for the first time N-myc-induced down-regulation of a gene implicated in signal
      transduction. Down-regulation of activin A could deprive neuroblastomas from a
      signal with growth-inhibitory activities toward the tumor and its stroma and
      thereby permit neuroblastoma progression.

PMID- 10913352
TI  - Dipeptidyl peptidase IV (DP IV/CD26) mRNA expression in PWM-stimulated T-cells is
      suppressed by specific DP IV inhibition, an effect mediated by TGF-beta(1).
AB  - Stimulation of human T-cells by pokeweed mitogen (PWM) results in a significant
      increase of IL-2, IFN-gamma, and DP IV mRNA expression as analyzed by
      quantitative RT-PCR. Here we show for the first time that the changes observed in
      cytokine mRNA expression are dose-dependently suppressed by the specific
      dipeptidyl peptidase IV inhibitor Lys[Z(NO(2))]-thiazolidide. Most interestingly,
      the inhibition of DP IV activity leads to a decrease in mRNA expression of the
      enzyme itself. Furthermore, evidence is provided that this suppression is
      mediated by TGF-beta(1). The presented data fit into the hypothesis that
      inhibition of DP IV leads to the induction of TGF-beta(1), which in turn provokes
      an arrest of cell cycle in late G(1).

PMID- 10913353
TI  - Phosphodiesterases 4D and 7A splice variants in the response of HUVEC cells to
      TNF-alpha(1).
AB  - The mRNA accumulation of phosphodiesterases PDE4D and PDE7A was studied by RNA
      blot analysis in human umbilical vein endothelial cells (HUVEC) incubated with
      TNFalpha for different periods. A contrasting behaviour was observed in the mRNA
      accumulation of the two genes. Further analysis by RT-PCR of the PDE4D and PDE7A
      splice variants gave different accumulation patterns which may indicate that
      differential splicing has a role in the regulation of these enzymes. Three
      previously undescribed PDE4D isoforms, with different accumulation patterns, were
      also detected. They code for truncated PDE4D isoforms, which could participate in
      the regulation of PDE4D activity.

PMID- 10913354
TI  - Application of hydrostatic pressure facilitates ex vivo adenovirus gene transfer
      into rabbit aortas.
AB  - We investigated whether application of hydrostatic pressure facilitates ex vivo
      adenovirus gene transfer into rabbit aortas. Assay of beta-galactosidase activity
      was performed in the aortas subjected to adenovirus encoding LacZ gene (Ad-LacZ)
      transfer. Application of hydrostatic pressure at 8 atmospheres during Ad-LacZ
      gene transfer (10(10) pfu/mL, 10 min) to aortic segments resulted in an
      approximately 4.5-fold increase in transgene efficiency. X-Gal staining showed
      predominant beta-galactosidase activity in the endothelial and the adventitial
      cells in the aorta subjected to pressure-supported Ad-LacZ gene transfer. Then we
      examined the effect of heme oxygenase-1 (HO-1), which catabolizes heme to carbon
      monoxide and biliverdin, by transferring adenovirus encoding HO-1 (Ad-HO-1) into
      rabbit aortas using this pressurization system. The Ad-HO-1-infected aortic
      segment showed a significantly decreased contractile response to phenylephrine
      compared to the Ad-LacZ-infected aortic segment. Pressure-supported adenovirus
      gene transfer may increase the feasibility of exploiting intraoperative
      adenovirus-mediated gene transfer.

PMID- 10913356
TI  - RNA interference for the organizer-specific gene Xlim-1 in Xenopus embryos.
AB  - Double-stranded RNA (dsRNA) interferes with gene expression in various species, a
      phenomenon known as RNA interference (RNAi). We show here that RNAi is also
      effective in modifying gene expression in Xenopus embryos. First, expression of
      an exogenous luciferase gene as a reporter in embryos was reduced by coinjection
      with dsRNA corresponding to the luciferase gene. Next, injection of dsRNA for
      Xlim-1, a homeobox gene suggested to be involved in Spemann organizer functions,
      reduced the endogenous level of Xlim-1 mRNA and produced embryos with reduced
      eyes or anterior truncation at high efficiency. In addition, injection of an
      antisense expression construct of Xlim-1 elicited phenotypes very similar to
      those of Xlim-1 dsRNA-injected embryos. These results indicate the effectiveness
      of RNAi for loss of function studies in Xenopus embryos, and the importance of
      Xlim-1 in head formation.

PMID- 10913355
TI  - PAL31, a novel nuclear protein, expressed in the developing brain.
AB  - We cloned a cDNA encoding a novel protein (PAL31) predominantly expressed in the
      fetal rat brain by differential display. PAL31 contains leucine-rich repeat
      domains, a highly acidic region and a putative nuclear localization signal. PAL31
      has 50-70% similarity to SSP29, APRIL, LANP, PHAP I, and PP32. Expression of
      PAL31 mRNA in the brain was high during the fetal period and decreased after
      birth. Immunohistochemical studies showed that PAL31 is expressed in the entire
      embryonic brain, whereas in the adult brain its expression is restricted to the
      subventricular zone where there are neural progenitor cells. It was also revealed
      that PAL31 is colocalized with PCNA in the nucleus, indicating that the PAL31
      expression is developmentally regulated. Considering the primary structure of
      PAL31 and its spatiotemporal expression pattern, PAL31 is a novel nuclear protein
      related to the development of the brain through the proliferation of neuronal
      cells.

PMID- 10913357
TI  - Potent and competitive inhibition of malic enzymes by lanthanide ions.
AB  - The catalytic activity of malic enzyme (ME), a member of a new class of oxidative
      decarboxylases, requires the presence of divalent cations (Mn(2+), Mg(2+), and
      others). The crystal structure at 2.9 A resolution of human mitochondrial NAD(+)
      dependent malic enzyme in a ternary complex with NAD(+) and the lanthanide ion
      Lu(3+), which has similar radius as Mn(2+), reveals a new conformation of the
      enzyme. The active site in this ternary complex is in an open form, while the
      organization of the tetramer of the enzyme actually resembles that with a closed
      active site. The Lu(3+) ion is bound to the enzyme at the same site as Mn(2+).
      Kinetic studies showed that Lu(3+) is a potent inhibitor of both the human
      NAD(P)(+)-dependent ME and the NADP(+)-dependent ME from pigeon liver, and is
      competitive with respect to the divalent cation, consistent with the structural
      information.

PMID- 10913359
TI  - Accessibility of the high-mannose glycans of glycoprotein gp120 from human
      immunodeficiency virus type 1 probed by in vitro interaction with mannose-binding
      lectins.
AB  - The direct interaction of mannose-specific plant lectins with gp120 of HIV-1 was
      studied by surface plasmon resonance. Inhibition experiments indicated that
      exposed high mannose type glycans play a key role in the interaction. Most of the
      lectins specifically accommodate outer alpha1,2-, alpha1,3-, or alpha1,6-linked
      di- or trimannosides, and especially legume lectins, also interact with the
      trimannoside core of the complex type glycans. The unexpected affinity of some
      lectins towards gp120 presumably results from conformational differences in their
      binding sites. These results demonstrate that mannose-specific plant lectins are
      powerful tools to study the accessibility and elucidate the function of the gp120
      glycans in the recognition and infection of the host cells by HIV-1.

PMID- 10913358
TI  - V642I APP-inducible neuronal cells: a model system for investigating Alzheimer's
      disorders.
AB  - APP is a precursor of beta amyloid deposited in Alzheimer's disease (AD).
      Although genetic studies established that mutations in APP cause familial AD
      (FAD), the mechanism for neuronal death by FAD mutants has not been well
      understood. We established neuronal cells (F11/EcR/V642I cells) in which V642I
      APP was inducibly expressed by ecdysone. Treatment with ecdysone, but not
      vehicle, killed most cells within a few days, with rounding, shrinkage, and
      detachment as well as nuclear fragmentation. Death was suppressed by Ac-DEVD-CHO
      and pertussis toxin. Electron microscopic analysis revealed that apoptosis
      occurred in ecdysone-treated cells. V642I-APP-induced death was suppressed by the
      anti-AD factors estrogen and apoE2. These data demonstrate not only that
      expression of this FAD gene causes neuronal apoptosis, but that F11/EcR/V642I
      cells, the first neuronal cells with inducible FAD gene expression, provide a
      useful model system in investigating AD disorders.

PMID- 10913360
TI  - alpha-Crystallin facilitates the reactivation of hydrogen peroxide-inactivated
      rhodanese.
AB  - It was previously shown that rhodanese, inactivated with hydrogen peroxide, could
      only be reactivated in the presence of a reductant or the substrate thiosulfate
      if these reagents were added soon after inactivation and if the oxidant was
      removed. Here, we report on the facilitated reactivation (75%) of hydrogen
      peroxide-inactivated rhodanese by the chaperone alpha-crystallin. Reactivation by
      the chaperone still required a reductant and thiosulfate. Without alpha
      crystallin, but in the presence of the reductant and thiosulfate, the inactivated
      enzyme regained about 39% of its original activity. The alpha-crystallin-assisted
      reactivation of hydrogen peroxide-inactivated rhodanese was independent of ATP.
      Further, we found, that alpha-crystallin interacted transiently, but could not
      form a stable complex with hydrogen peroxide-inactivated rhodanese. Unlike in
      prior studies that involved denaturation of rhodanese through chemical or thermal
      means, we have clearly shown that alpha-crystallin can function as a molecular
      chaperone in the reactivation of an oxidatively inactivated protein.

PMID- 10913361
TI  - Age-related effects of TGF-beta on proteoglycan synthesis in equine articular
      cartilage.
AB  - The synthesis of proteoglycans was measured in normal equine articular cartilage
      of ages 9 months to 20 years and the effect of TGF-beta1 on this activity was
      investigated. The rate of incorporation of [(35)S]Na(2)SO(4) decreased with age
      as did the responsiveness of the tissue to the growth factor. The enhanced
      synthesis of proteoglycan induced at all ages by TGF-beta1 was down-regulated by
      IL-1 beta and retinoic acid. The expression of mRNA for TGF-beta1, 2, and 3 was
      also measured, and although the level of TGF-beta1 was highest at all ages, the
      expression of each growth factor decreased with age.

PMID- 10913362
TI  - Rapid inhibition by sodium azide of the phosphoinositide-mediated calcium
      response to serotonin stimulation in human platelets: preservation in Alzheimer's
      disease.
AB  - The effect of sodium azide (NaN(3)) upon platelet Ca(2+) signalling has been
      investigated. A 60 s preincubation with 1 mM NaN(3) reduced the Ca(2+) response
      to 1 microM serotonin without a corresponding reduction in the responses to 52
      mU/ml thrombin or 70 microM beta-amyloid(25-35) (A beta(25-35)). The effect of
      NaN(3) upon the response to serotonin, which was not blocked by either
      glutathione ethyl ester (GTEE) or dithiothreitol (DTT), was similar in platelets
      obtained from patients with Alzheimer's disease and from age- and gender-matched
      controls. After a preincubation time of 5 min was used, the Ca(2+) response to
      thrombin was greatly reduced by 1 mM NaN(3), but not by 50 microM 4
      hydroxynonenal (HNE, 50 microM). Platelet levels of HNE and malondialdehyde were
      not significantly affected by up to 30 min of incubation with NaN(3) at room
      temperature. It is concluded that the rapid effect of NaN(3) upon the Ca(2+)
      response to serotonin in human platelets is not mediated by an inhibition of
      cytochrome c oxidase, and is due to an action proximal to phosphoinositide
      specific phospholipase C.

PMID- 10913363
TI  - The biphasic effects of nitric oxide in primary rat osteoblasts are cGMP
      dependent.
AB  - Nitric oxide is a gas radical regulating cell behaviour in the cardiovascular,
      immune, and central nervous systems. It has now been established as an important
      signalling molecule in bone. However, the effects of this gas radical on
      osteoblastic function are still unclear; in fact, while NO seems to be involved
      in anabolic processes mediated by mechanical strain, sex hormones and fracture
      healing, it also mediates catabolic processes in response to inflammation. We
      show here that a slow and moderate release of nitric oxide stimulates the
      replication of primary rat osteoblasts and alkaline phosphatase activity, while a
      rapid release and high concentrations of NO inhibit proliferation and induce
      apoptosis. We demonstrate that both the stimulatory and apoptosis-inducing
      effects of NO on primary osteoblasts are mediated by the second messenger cGMP,
      since both are abolished by the guanylate cyclase inhibitor ODQ.

PMID- 10913364
TI  - Nitric oxide regulates the aggregation of stimulated human neutrophils.
AB  - Neutrophil aggregation is mediated by both CD18 integrin and L-selectin. Nitric
      oxide attenuates the integrin-mediated adhesion of neutrophils to collagen and to
      endothelium and may therefore affect aggregation as well. FMLP-stimulated
      neutrophils exposed to l-arginine showed increased and prolonged aggregation,
      whereas cells pretreated with L-NAME did not differ from FMLP-stimulated
      controls. Nitric oxide is known to induce ADP ribosylation of G-actin, which
      inhibits polymerization. We detected equivalent levels of total F-actin in cells
      pretreated with l-arginine or L-NAME and non-pretreated controls. However,
      neutrophils pretreated with l-arginine and stimulated by CD18 integrin cross
      linking exhibited a more limited increase in total F-actin, compared to control
      and L-NAME-pretreated cells. Thus at least two signaling pathways may be involved
      FMLP-stimulated aggregation, mediated by CD18 integrins. More specifically, it is
      plausible that FMLP-receptor signaling upregulates CD18 integrins and endogenous
      NO subsequently modulates CD18-mediated signaling to prolong aggregation,
      possibly through ADP-ribosylation of actin.

PMID- 10913365
TI  - A rolling-circle plasmid from Psychrobacter sp. TA144: evidence for a novel rep
      subfamily.
AB  - In this paper we report the cloning and sequencing of two small plasmids, pTAUp
      and pTADw, from the Antarctic Gram-negative Psychrobacter sp strain TA144. The
      observation that pTAUp contains a putative Rep-coding gene (Psyrep) suggested
      that its duplication occurs via a rolling-circle replication mechanism. This
      hypothesis was confirmed by the identification of the pTAUp single-stranded DNA
      form. The putative pTAUp plus origin of replication was found at the 3' end of
      the Psyrep by using an in vivo complementation assay. Structural similarities at
      the level of (i) gene organization, (ii) protein sequence, and (iii) nick site
      sequences strongly suggest that the psychrophilic enzyme belongs to a new
      subfamily of replication enzymes.

PMID- 10913366
TI  - Membrane permeability modifications are involved in antibiotic resistance in
      Klebsiella pneumoniae.
AB  - Two Klebsiella pneumoniae strains selected according to their high cross
      resistance pattern to cephalosporins were characterized by (i) outer membrane
      protein content such as OmpA or nonspecific porins, (ii) MICs of various
      cephalosporins and unrelated antibiotics, (iii) beta-lactamase production, and
      (iv) active efflux of fluoroquinolones. An association of porin deficiency and
      beta-lactamase production induced a noticeable cephalosporin resistance. In
      addition to these mechanisms, the presence of an active efflux participating in
      high-level fluoroquinolone resistance was identified in one strain. The decrease
      of antibiotic uptake associated with efflux explains the Klebsiella adaptation
      against the drugs present in the environment.

PMID- 10913367
TI  - Immunomodulatory potential of thymulin-Zn(2+) in the alveolar epithelium:
      amelioration of endotoxin-induced cytokine release and partial amplification of a
      cytoprotective IL-10-sensitive pathway.
AB  - The immunomodulatory potential of thymulin in the perinatal epithelium is not
      well characterized. In an in vitro model of fetal alveolar type II epithelial
      cells, we investigated the exhibition of an anti-inflammatory activity of this
      peptide hormone. Thymulin selectively ameliorated, in a dose-dependent manner,
      the endotoxin-induced release of IL-1 beta (IC(50) = 657 ng. ml(-1)), but showed
      no inhibitory effect on IL-6 and TNF-alpha. Zinc, an anti-inflammatory
      antioxidant, which is required for the biological activity of thymulin, reduced
      the secretion of IL-1 beta (IC(50) = 62 microM), TNF-alpha (IC(50) = 1000
      microM), and, to a lesser extent, IL-6. This cation (100 microM) amplified the
      effect of thymulin on IL-1 beta and TNF-alpha (IC(50) < 0.1 ng. ml(-1)), but not
      on IL-6. Analysis of whether thymulin is up-regulating a counterpart anti
      inflammatory signaling loop revealed the involvement of an IL-10-sensitive
      pathway. These results indicate that thymulin acts as a novel dual
      immunoregulator by enhancing an anti-inflammatory cytoprotective response and
      depressing an inflammatory signal, an effect synergistically amplified, in part,
      by cationic zinc.

PMID- 10913368
TI  - Activation of ERK1/2 and cPLA(2) by the p55 TNF receptor occurs independently of
      FAN.
AB  - The generation of proinflammatory eicosanoids in response to tumor necrosis
      factor (TNF) involves the activation of cytosolic phospholipase A(2) (cPLA(2)),
      presumably by phosphorylation through extracellular signal-regulated kinases
      (ERK). Earlier results had suggested that a pathway involving the p55 TNF
      receptor (TNF-R55), neutral sphingomyelinase (N-SMase), and c-Raf-1 activates ERK
      and cPLA(2). We have previously shown that a cytoplasmic region of TNF-R55
      distinct from the death domain regulates the activation of N-SMase through
      binding of the adapter protein FAN. Analysis of embryonal fibroblasts from FAN
      knockout mice revealed that TNF-induced activation of both ERK and cPLA(2) occurs
      without involvement of FAN. Furthermore, we provide evidence that the TNF
      dependent activation of ERK and cPLA(2) requires the intact death domain of TNF
      R55. Finally, we demonstrate that in murine fibroblasts cPLA(2) is phosphorylated
      in response to TNF solely by ERK, but not by p38 mitogen-activated protein
      kinase, suggesting a signaling pathway from TNF-R55 via the death domain to ERK
      and cPLA(2).

PMID- 10913369
TI  - Dithiocarbamates inhibit hematopoiesis via a copper-dependent mechanism.
AB  - Dithiocarbamates (DTC), an important class of therapeutic and industrial
      chemicals, have alternatively been reported to be either beneficial or toxic to
      the hematopoietic and immune systems. In the present study, we investigated the
      potential of dimethyl- and diethyl-dithiocarbamate to alter clonogenic response
      of primary human CD34(+) bone marrow cells in vitro. Our results demonstrate that
      both compounds are potent inhibitors of clonogenic response in human CD34(+) bone
      marrow cells, suppressing cytokine-induced colony formation at concentrations
      between 100 and 500 nM. Pretreatment of bone marrow cells for 1 h with very high
      doses of DTC (30 microM) had no effect on colony formation. DTCs are known
      inhibitors of nuclear factor-kappa B (NF-kappa B); however, data presented herein
      demonstrate that DTC do not inhibit cytokine activation of NF-kappa B in CD34(+)
      bone marrow cells. Additional experiments demonstrate that DTCs induce a dose
      related increase in apoptosis, potentially acting via a cytotoxic mechanism. We
      further demonstrate that the addition of copper sulfate greatly potentiates the
      hematotoxicity of DTC and that the addition of a copper-specific chelator
      completely abrogates DTC clonogenic suppression. These data support a role for
      copper in DTC-induced hematotoxicity.

PMID- 10913370
TI  - TGF-beta 1 modulated the expression of alpha 5 beta 1 integrin and integrin
      mediated signaling in human hepatocarcinoma cells.
AB  - Integrins are a family of cell surface adhesion molecules which mediate cell
      adhesion and initiate signaling pathways that regulate cell spreading, migration,
      differentiation, and proliferation. TGF-beta is a multifunctional factor that
      induces a wide variety of cellular processes. In this study, we show that, TGF
      beta 1 treatment enhanced the amount of alpha 5 beta 1 integrin on cell surface,
      the mRNA level of alpha 5 subunit, and subsequently stimulated cell adhesion onto
      a fibronectin (Fn) and laminin (Ln) matrix in SMMC-7721 cells. TGF-beta 1 could
      also promote cell migration. Furthermore, our results showed that TGF-beta1
      treatment stimulated the tyrosine phosphorylation level of FAK, which can be
      activated by the ligation and clustering of integrins. PTEN can directly
      dephosphorylate FAK, and the results that TGF-beta 1 could down-regulate PTEN at
      protein level suggested that TGF-beta 1 might stimulate FAK phosphorylation
      through increasing integrin signaling and reducing dephosphorylation of FAK.
      These studies indicated that TGF-beta 1 and integrin-mediated signaling act
      synergistically to enhance cell adhesion and migration and affect downstream
      signaling molecules of hepatocarcinoma cells.

PMID- 10913372
TI  - cis-9,10-Methylenehexadecanoic acid inhibits contractility and actomyosin ATPase
      activity of guinea pig myocardium.
AB  - Superfusion with a cyclopropane fatty acid, cis-9, 10-methylenehexadecanoic acid
      (10-300 microM), reduced the contractility of papillary muscle isolated from
      guinea pigs in a dose-dependent manner. cis-9,10-Methylenehexadecanoic acid also
      inhibited the Mg(2+)-ATPase activity of guinea pig papillary myocardium by about
      40% at 400 microM. Since cis-9, 10-methylenehexadecanoic acid 4 microM inhibited
      the K(+)-EDTA-ATPase activity inherent in myosin's catalytic activity by about
      25%, the fatty acid was thought to interact with the catalytic center of the
      myosin molecule.

PMID- 10913371
TI  - Transcriptional activation function of zinc finger protein TIS11 and its negative
      regulation by phorbol ester.
AB  - TIS11, a CCCH zinc finger protein, is one of the typical growth factor-inducible
      nuclear proteins. We found that TIS11 possesses the potential to activate
      transcription when fused to the GAL4 DNA binding domain and transiently
      cotransfected into rat pheochromocytoma PC12 cells along with a GAL4-responsive
      luciferase reporter gene. The study with deletion mutants of TIS11 revealed that
      the major transactivation region is located at the N-terminal 101 amino acid
      residues and that the remaining central and C-terminal region had a moderate
      transactivational activity. In addition, the transactivational activity of TIS11
      was found to be significantly reduced by treating the transfectants with phorbol
      12-myristate 13-acetate (PMA). PMA-induced inactivation of TIS11 was blocked by
      calphostin C, a protein kinase C inhibitor, and PD98059, a mitogen-activated
      protein (MAP) kinase kinase inhibitor. These results suggested that TIS11
      functions as a positive transcriptional regulator and that the protein kinase
      C/MAP kinase signaling cascade is involved in negative regulation of TIS11 by
      PMA.

PMID- 10913373
TI  - Tools for evaluating ubiquitin (UbC) gene expression: characterization of the rat
      UbC promoter and use of an unique 3' mRNA sequence.
AB  - UbC is one of three members of the ubiquitin gene family. We have cloned the rat
      UbC promoter and used primer extension analysis to map the UbC site of
      transcription initiation to 63 bp upstream of the putative first intron. We used
      a rat UbC promoter-luciferase reporter minigene to transfect H9c2 cardiomyocytes,
      HepG2 hepatocytes, CaCo2 colon cells, NIH3T3 fibroblasts or L6 myocytes and found
      the rat UbC promoter has constitutive activity. We also showed that dexamethasone
      stimulated the UbC promoter in L6 myocytes. Finally, we showed that a UbC
      specific sequence at the 3' end of the rat UbC mRNA transcript can be used to
      selectively and quantitatively measure UbC: (1) mRNA using a RNase protection
      assay, and (2) transcription using a nuclear run-off assay to measure the rate of
      transcription of the UbC gene. These findings will be useful in studying the
      regulation of the UbC gene.

PMID- 10913374
TI  - Endothelial cells downregulate expression of the 70 kDa heat shock protein during
      hypoxia.
AB  - Hsp70 is induced by hypoxia in most mammalian cell types and contributes to their
      ability to survive hypoxic episodes. However, little is known about Hsp70
      expression in the hypoxia-tolerant endothelial cells (ECs). We investigated the
      effect of hypoxia on Hsp70 in human microvascular endothelial HMEC-1 cells.
      Reduction of pO(2) to 2.5% of normal for 20 h stimulated lactate production and
      the activity of glycolytic enzymes. This metabolic adaptation to hypoxia was
      accompanied by a remarkable reduction of Hsp70 on the protein level and on the
      mRNA level. Approximately 12 h after the hypoxic period Hsp70 expression reached
      pre-hypoxia levels again. Since ECs are adapted to the low oxygen tension of the
      vasculature they are confronted with a supraphysiological oxygen level during in
      vitro culture. We suppose that the high Hsp70 under these conditions reflects a
      stress response which disappears at the more physiological reduced oxygen tension
      during hypoxia.

PMID- 10913375
TI  - Interaction of yeast importin alpha with the NLS of prothymosin alpha is
      insufficient to trigger nuclear uptake of cargos.
AB  - A proliferation-related human protein prothymosin alpha displays exclusively
      nuclear localization when produced in human and Saccharomyces cerevisiae cells,
      whereas its isolated bipartite NLS confers nuclear targeting of the GFP reporter
      in human but not in yeast cells. To test whether this observation is indicative
      of the existence of specific requirements for nuclear targeting of proteins in
      yeast, a set of prothymosin alpha deletion mutants was constructed. Subcellular
      localization of these mutants fused to GFP was determined in yeast and compared
      with their ability to bind yeast importin alpha (Srp1p) in vitro. The NLS of
      prothymosin alpha turned out to be both necessary and sufficient to provide
      protein recognition by importin alpha. However, the NLS-importin alpha
      interaction did not ensure nuclear targeting of prothymosin alpha derivatives.
      This defect could be complemented by adding distinct prothymosin alpha sequences
      to the NLS-containing import substrate, possibly by providing binding site(s) for
      additional components of the yeast nuclear import machinery.

PMID- 10913376
TI  - Cholesterol modulates vascular reactivity to endothelin-1 by stimulating a pro
      inflammatory pathway.
AB  - Hypercholesterolemia (HC) is associated with coronary endothelial dysfunction and
      increased circulating levels of endothelin-1. We show that pre-treatment of
      intact rat aortic rings with cholesterol synergistically enhances the
      vasoconstriction induced by endothelin-1 suggesting that elevated levels of
      cholesterol may predispose to hypertension by modulating the vascular reactivity
      to endogenous vasoconstrictors. Moreover, we report that SB202190, a selective
      inhibitor of p38 MAPK, and PD98059 an inhibitor of MEK1/2 are able to abolish the
      vasoactive properties of cholesterol. MK-886, an inhibitor of 5-lipoxygenase is
      inefficient at blocking the vasoactive properties of cholesterol whereas NS-398,
      a selective inhibitor of cyclooxygenase-2 (COX-2) completely abolishes
      cholesterol-induced vasoconstriction. In intact rat aortae, cholesterol
      stimulates prostaglandin E(2) and prostaglandin F(2 alpha) production, an effect
      that can be completely prevented by inhibiting p38 MAPK, or COX-2. In vitro,
      cholesterol appears to stimulate a similar pro-inflammatory pathway in human
      cerebrovascular smooth muscle cells. Disruption of the MAPK/COX-2 pathway may
      represent a valuable therapy to block the hypertension associated with HC, as
      well as the development of atherosclerosis.

PMID- 10913377
TI  - N-ethylmaleimide-sensitive factor is associated with the nuclear envelope.
AB  - N-Ethylmaleimide-sensitive factor (NSF) is an ATPase involved in many membrane
      fusion events within the exocytic and endocytotic pathways. In the present study
      we showed that NSF is associated with the nuclear envelope. Golgi-associated NSF
      was released from membranes upon incubation with Mg(2+)-ATP, reflecting the
      disassembly of a complex consisting of NSF, soluble NSF attachment proteins
      (SNAPs), and SNAP receptors (SNAREs). In contrast nuclear envelope-associated NSF
      in interphase cells was not released by the same treatment. During mitosis,
      however, it was released from nuclear membranes by Mg(2+)-ATP. These results
      suggest that the binding mode of nuclear membrane-associated NSF changes during
      the cell cycle.

PMID- 10913378
TI  - Protein tyrosine phosphorylation induced by ubiquitin-like polypeptide in murine
      T helper clone type 2.
AB  - Ubi-L, an isoform of the monoclonal nonspecific suppressor factor (MNSF), is an
      8.5-kDa ubiquitin-like polypeptide. Ubi-L shows an antigen-nonspecific
      immunosuppressive action on various target cells including murine T helper type 2
      clone, D10 cells. Most recently, we have characterized the biochemical nature of
      the receptor for Ubi-L. In this study, we observed that Ubi-L receptor ligation
      rapidly and transiently stimulated tyrosine phosphorylation of 65- and 31-kDa
      proteins in concanavalin A-activated D10 cells. The addition of neutralizing
      antibody to Ubi-L receptor inhibited the protein tyrosine phosphorylations and
      the Ubi-L-mediated suppression of IL-4 production by D10 cells. Genistein, a
      tyrosine kinase inhibitor, also reduced the induction of these protein tyrosine
      phosphorylations. IFNgamma, which is also known to inhibit the proliferative
      response of D10 cells, showed a synergistic effect with Ubi-L. Interestingly,
      IFNgamma enhanced the Ubi-L-induced tyrosine phosphorylation of the 31-kDa
      protein. These results suggest that tyrosine phosphorylation may be a key step in
      the initiation of the Ubi-L receptor-mediated transmembrane signaling.

PMID- 10913379
TI  - The treatment of cranial germ cell tumours.
AB  - Germ cell tumours of the central nervous system (CNS) include many subtypes whose
      response to treatment varies, even though the symptoms and radiological
      appearances are similar. Five-year survival rates are 96% for germinomas, 100%
      for mature teratomas, 67% for immature teratomas and 69% for immature teratomas
      mixed with germinomas; for beta-HCG secreting germinomas the rate is only 38%.
      Patients with choriocarcinoma, embryonal carcinoma, or yolk sac tumour have the
      lowest survival rates; patients with germinoma or mature teratoma have longer
      survival rates. Although a wider resection is associated with a higher rate of
      survival for patients with non-germinomatous germ cell (NGGC) tumours, to date an
      aggressive surgical approach has been advocated only for pineal region tumours,
      but not for hypothalamic/neurohypophyseal tumours. Beside the delayed injury
      induced by radiotherapy, the late injury induced by chemotherapy is becoming
      increasingly evident. Cisplatin is considered an indispensable drug, but it may
      cause renal damage, ototoxicity, peripheral neuropathy and sterility, while
      etoposide is associated with an excess frequency of second neoplasms. Taking into
      account all of the published literature, the following therapeutic options are
      suggested: in pure germinoma tumours (GT) radiotherapy alone will usually ensure
      adequate control of the disease, and the long-term sequelae may be limited by
      reducing the dose delivered, as was proposed for germ cell testicular tumours, to
      30 Gy to limited fields plus 25-30 Gy to the spinal axis if there is disseminated
      disease. In cases of recurrence, which should be uncommon, patients may be
      rescued with both radiotherapy and chemotherapy. In NGGC tumours, the prognosis
      is more unfavourable and there is often dissemination to the spine at diagnosis;
      however, the tumour's high chemosensitivity suggests neoadjuvant treatment
      chemotherapy with cisplatin and etoposide for three cycles followed by
      consolidation radiotherapy with 40 Gy to the limited fields plus 30 Gy to the
      spinal axis if disseminated. In our opinion, a higher dose of radiotherapy in
      cases in which chemotherapy does not achieve a radiological complete remission is
      not advisable, because very often the residual radiological abnormality does not
      represent biologically active tumour but differentiated forms such as mature
      teratoma. The challenge for 2000 is to both cure these patients, and avoid the
      late and permanent sequelae of radiation and/or chemotherapy that may
      subsequently impair quality of life.

PMID- 10913380
TI  - Current status and future perspectives in gastric cancer management.
AB  - Gastric cancer is still a major health problem and a leading cause of cancer
      mortality despite a worldwide decline in incidence. Environmental and
      Helicobacter pylori (Hp) acting early in life in a multistep and multifactorial
      process may cause intestinal type carcinomas, whereas genetic abnormalities are
      related more to the diffuse type of disease. Primarily due to early detection of
      the disease, the results of treatment for gastric cancer have improved in Japan,
      Korea and several specialized Western centres. Surgery offers excellent long-term
      survival results for early gastric cancer (EGC). Advances in diagnostic and
      treatment technology have contributed to a trend towards minimal invasive surgery
      such as endoscopic mucosal resection (EMR) and laparoscopic surgery for selected
      mucosal cancers. In the Western world, however, more than 80% of patients at
      diagnosis have an advanced gastric cancer with a poor prognosis. The aim of
      surgery is complete removal of the tumour (UICC R0-resection), which is known to
      be the only proven, effective treatment modality and the most important treatment
      related prognostic factor. Gastrectomy with preservation of the spleen and
      pancreas in most cases is the standard procedure. However, at present there is no
      consensus about the optimal extent of lymph-node dissection. The hypothesis that
      extended (D2) lymph-node dissection leads to improved survival has not been
      confirmed in randomized trials. Results from specialized centres and ongoing
      multi-institutional randomized trials, however, indicate that D2 dissection, with
      preservation of the spleen and pancreas, can be performed with the same safety as
      a D1 dissection. Furthermore, in 50% of patients with node-positive disease, the
      extraperigastric N2 nodes are involved (N2 disease) and thus an R0-resection is
      achievable only by a D2 node dissection resulting in a 5-year survival of about
      30% for such patients. However, even after a D2 node dissection with curative
      potential, disease recurs in two-thirds of patients with locally advanced gastric
      cancer (LAGC) and is rapidly fatal. The need for an adjuvant treatment is
      obvious, but at present there is no such treatment of proven effectiveness.
      Promising results with preoperative chemotherapy, which increases the R0
      resection rate, and intra-or early postoperative intraperitoneal
      chemohyperthermia to prevent peritoneal dissemination have been reported.
      However, randomized trials are necessary before these combined treatments become
      widely accepted. Present data indicate that the treatment of gastric cancer has
      become more and more sophisticated with a tailored therapy for individual cases.
      Treatment includes a broad spectrum of therapeutic options from EMR for selected
      mucosal cancers to aggressive combined treatment for LAGC. Precise knowledge of
      patterns of recurrence and metastases, critical evaluation of clinicopathologic
      variables, integration of high technology into diagnosis to predict accurately
      pre-treatment staging, and the surgeon's ability to perform minimally invasive
      surgery and D2 node dissection technique are necessary for an appropriate
      treatment option. All these prerequisites are best ensured by management in
      experienced surgical oncology units.

PMID- 10913381
TI  - Chemistry, pharmacology and pharmacokinetics of N,N',N" 
      triethylenethiophosphoramide (ThioTEPA).
AB  - N,N',N" -triethylenethiophosphoramide (thioTEPA) is a trifunctional alkylating
      agent with a broad spectrum of antitumour activity developed in the 1950s. The
      drug is now experiencing renewed interest as it appears to be one of the most
      effective anticancer drugs in high dose regimens. Despite many years of
      experience with thioTEPA, pharmacologic data are incomplete and controversy
      remains with respect to the dose-dependent pharmacokinetics of thioTEPA. In
      recent years greater insight has been obtained into the metabolism of thioTEPA,
      but there is still a gap between the total urinary excretion of thioTEPA and
      metabolites and the alkylating activity. In vivo and in vitro studies show that
      alkylation of DNA by thioTEPA can follow two pathways, but it remains unclear
      which pathway represents the precise mechanism of action. The currently available
      sensitive analytical methods for thioTEPA and its metabolites can be used to
      elucidate the many questions that still exist even so many years after its
      introduction. An overview is given of the chemistry, pharmacology, clinical use
      and toxicity of thioTEPA as well as its pharmacokinetics and analytical methods
      for thioTEPA and its metabolites.

PMID- 10913382
TI  - Monoclonal antibody therapy for solid tumors.
AB  - Monoclonal antibody therapy for solid tumors has many theoretical attractions and
      a long history. Until recently, with the approval and widespread use of rituximab
      (Rituxan) and trastuzumab (Herceptin), monoclonal antibody therapy for tumors had
      not had significant success. This article reviews basic theories behind antibody
      development and their clinical implementation as treatment for solid tumors.
      Medline was searched for articles over the past 15 years dealing with laboratory
      and clinical applications of antibody therapy for solid tumors. In addition,
      American Society of Clinical Oncology (ASCO) abstracts from the past 3 years were
      reviewed to complement the Medline search. This article focuses on treatment for
      common solid tumors, including breast, colon and lung cancers.

PMID- 10913383
TI  - Herceptin (trastuzamab) in advanced breast cancer.
AB  - Herceptin (trastuzamab, Genentech, San Francisco, CA, USA) prolongs survival in
      metastatic breast cancer patients whose tumours overexpress the HER2/neu protein.
      Compared with chemotherapy alone, patients receiving chemotherapy and Herceptin
      have a significantly longer time to progression, a higher response rate and a
      longer duration of response. These effects are most marked in first-line
      treatment of metastatic disease. The addition of Herceptin is associated with few
      additional side-effects, apart from cardiac toxicity in patients concurrently
      receiving anthracyclines. As such, it seems reasonable for Herceptin to become
      considered as one of the routine treatment options in metastatic breast cancer.
      It would therefore be appropriate for HER2 status testing to be incorporated into
      the assessment of all patients with metastatic disease. The use of this
      medication will be limited by its cost. Furthermore, data are lacking on
      appropriate treatments durations in responders.

PMID- 10913384
TI  - Breast cancer risk following irradiation for Hodgkin's disease.
AB  - Radiation is commonly used to treat early-stage Hodgkin's disease. As the risk of
      recurrent Hodgkin's disease decreases as time from treatment elapses, the risk of
      radiation-induced breast cancer rises. Women irradiated between the time of
      puberty and the age of 30 are at the highest risk. The median time to breast
      cancer following radiation in this age group is approximately 15 years, usually
      when women are aged between 30 and 40, and often before regular breast screening
      is implemented. Risk factors associated with breast cancer development include
      age at irradiation, time since treatment and the radiation dose received. Current
      screening for breast cancer after Hodgkin's disease is inconsistent. In this
      article we review breast development, mechanisms of radiation-induced
      carcinogenesis, and findings from retrospective studies on Hodgkin's disease and
      breast cancer. We also review future considerations of management, including
      assessment of risk awareness in these women, guidelines for follow-up and
      screening, and chemoprevention both during and after treatment of Hodgkin's
      disease. The literature reviewed was obtained from Medline using the key words:
      breast cancer, Hodgkin's disease and radiation-induced cancer. The search was
      limited to English language literature. Other sources include reference lists in
      books and published papers.

PMID- 10913386
TI  - Articles to appear in forthcoming issues of cancer treatment reviews

PMID- 10913385
TI  - Anaemia in cancer: pathophysiology and treatment.
AB  - Anaemia in cancer patients is multifactorial and may occur as a either a direct
      effect of the cancer, as a result of the cancer treatment itself, or due to
      chemical factors produced by the cancer. The clinical symptoms of anaemia vary
      according to the individual's capacity to respond to blood loss or reduced red
      cell production. The haematological features in anaemic patients depend on the
      different types of malignant disease. Clinical and laboratory evaluation, and
      examination of the bone marrow can provide important diagnostic clues in many
      cases. Decisions are commonly made based on subjective consideration rather than
      on objective data. Blood transfusion involves many hazards, some of which may be
      reduced or avoided. Erythropoietin (EPO) treatment has been found to be effective
      in preventing anaemia and in reducing the need for blood transfusions, although
      it would be useful to identify high-risk patient subgroups who would benefit most
      from this expensive treatment. In advanced cancer patients the use of blood
      transfusion should be evaluated on an individual basis, according to the presence
      of distressing symptoms and life expectancy. These measures are unlikely to have
      an effect in irreversible and progressive bleeding states.

PMID- 10913387
TI  - Clinical infectious diseases and the evolving human immunodeficiency virus
      epidemic.

PMID- 10913388
TI  - Frequency of serological evidence of Bordetella infections and mixed infections
      with other respiratory pathogens in university students with cough illnesses.
AB  - Banked acute-phase and convalescent-phase serum samples from a previous study of
      respiratory illness in university students were examined for significant (>/=2
      fold) increases in ELISA titers of IgA and IgG antibody to Bordetella pertussis
      filamentous hemagglutinin, pertactin, and fimbriae-2 and >/=4-fold titer
      increases to agglutinogens by agglutination. ELISA titers of antibody to
      pertussis toxin could not be determined because of technical problems. Chlamydia
      pneumoniae infections were diagnosed by culture or by a >/=4-fold increase in
      immunofluorescence assay titer or a single high titer (>/=512). Mycoplasma
      pneumoniae, influenza A and B, adenovirus, and respiratory syncytial virus
      infections were diagnosed by >/=4-fold increases in complement fixation titer or
      a single high titer (>/=64). There were 319 subjects with cough of >/=5 days'
      duration, and of these, 47 (15%) had significant increases in antibody to B.
      pertussis antigens; 26 (8%) had significant increases to fimbriae-2 or
      agglutinogens, indicative of B. pertussis infection, and 2 (1%) had evidence of
      non-B. pertussis bordetella infections. Seventeen (36%) had evidence of mixed
      infections or cross-reacting antibodies (influenza B infections, 5; adenovirus
      infections, 4; influenza A infections, 3; C. pneumoniae infections, 3; and M.
      pneumoniae infections, 2). Our findings suggest that bordetella infections are
      common in young adults with cough illnesses (incidence, 9%), and a surprising
      number of these are mixed infections with other respiratory pathogens.

PMID- 10913390
TI  - Assessment of the relationship between antimicrobial usage and susceptibility:
      differences between the hospital and specific patient-care areas.
AB  - Current evidence suggests that controlling antibiotic resistance requires the
      monitoring of both susceptibility trends and antimicrobial usage within specific
      patient-care areas of the hospital. To assess the differences between
      antimicrobial usage-versus-susceptibility relationships found in the hospital and
      those relationships found in specific patient-care areas, susceptibility and
      antimicrobial usage data collected over a 5-year period (1992-1996) at the
      Medical University of South Carolina were analyzed. For each area, the
      relationship between drug use and susceptibility was analyzed for 8 gram-negative
      organisms with respect to 19 different agents and for 3 staphylococci with
      respect to 10 agents with use of simple linear regression. The relationships
      found in the hospital had a poorer overall agreement with the relationships found
      in the intensive care units (ICUs; <20%) than they did with the relationships
      found in the non-ICUs ( approximately 65%). Surveillance should include both
      susceptibility and drug usage patterns in individual areas within an institution.

PMID- 10913389
TI  - Antibody responses to Bordetella pertussis antigens and clinical correlations in
      elderly community residents.
AB  - A serological study to determine the frequency of Bordetella pertussis infection
      in 100 adults aged >/=65 years was carried out over a 3-year period. Ten serum
      samples (collected every 4 months) from each subject were examined for IgA and
      IgG antibodies to the following B. pertussis antigens: pertussis toxin (PT),
      filamentous hemagglutinin (FHA), pertactin, and fimbriae-2. A >/=2-fold titer
      increase in ELISA units from one time period to the next was considered
      serological evidence of infection. The rate of serologically defined infection
      (i.e., in which there was an increase in titer against any antigen) was 19.7 per
      100 person-years. With the use of more specific criteria that indicate definite
      B. pertussis infection (>/=2-fold increase in titer to PT) and probable B.
      pertussis infection (>/=2-fold increase in titer to PT or >/=2-fold increase to
      fimbriae-2), the rates were 3.3 and 8.0 per 100 person-years, respectively. Fifty
      percent of individuals with definite B. pertussis infections had time-associated
      symptomatology. Antibody patterns over time suggest that antibody to FHA and
      perhaps to pertactin is stimulated by infections with other organisms, as well as
      B. pertussis infections. Our data suggest that symptomatic pertussis occurs in
      elderly individuals. Consideration should be given to immunization of the elderly
      with acellular pertussis vaccines.

PMID- 10913391
TI  - Polyclonal Staphylococcal endocarditis caused by genetic variability.
AB  - Cultures of blood obtained from a patient with Staphylococcus epidermidis
      prosthetic valve endocarditis yielded 15 strains of S. epidermidis. Genome
      macrorestriction and amplified fragment-length polymorphism analyses of these
      strains showed that they belonged to 4 different, very closely related clones,
      suggesting that they were the result of genetic variability of an infecting
      strain during the infectious episode. In vivo experiments in a rat model for
      foreign body infections using 1 of the S. epidermidis strains from the patient
      showed genetic variability similar to that of the infecting strain. In the rat
      model, we also detected the simultaneous presence of different clones that were
      identical to those isolated from our patient, thus confirming the possibility of
      genetic variability. It is important to note that the 4 clones isolated from our
      patient presented with 2 different antibiograms. Therefore, in cases of foreign
      device-related infections due to coagulase-negative staphylococci, the
      possibility of polyclonal infection has to be taken into account, particularly as
      regards differences in antibiotic susceptibility.

PMID- 10913392
TI  - Editorial response: coagulase-negative staphylococcal infections: A diagnostic
      and therapeutic challenge.

PMID- 10913393
TI  - Immunogenicity of a heptavalent pneumococcal conjugate vaccine in Apache and
      Navajo Indian, Alaska native, and non-native American children aged <2 years.
AB  - High rates of invasive pneumococcal disease have been described among infants
      living in various Native American communities. In this study, we evaluated the
      immunogenicity of a 7-valent pneumococcal vaccine consisting of serotypes 4, 6B,
      9V, 14, 18C, 19F, and 23F covalently linked to the outer membrane protein complex
      of Neisseria meningitidis in Apache and Navajo Indian, Alaska Native, and non
      Native American children. The vaccine was administered at ages 2, 4, and 6
      months; a booster dose was given at age 15 months. Levels of serotype-specific
      immunoglobulin G (IgG) were measured by a standardized enzyme-linked
      immunosorbent assay. The responses after 3 primary doses of vaccine were similar
      in all 3 groups of children, except for those to serotypes 14 and 23F. One month
      after the booster dose, geometric mean concentrations (GMCs) of serotype-specific
      IgG antibodies increased significantly in all 3 groups of children, compared with
      GMCs of IgG antibodies to pneumococcal serotypes before the booster dose.

PMID- 10913394
TI  - Detection of multiple reactive protein species by immunoblotting after
      recombinant outer surface protein A lyme disease vaccination.
AB  - Laboratory confirmation of the diagnosis of Lyme disease is based on the
      detection of an immune response to Borrelia burgdorferi. The serodiagnosis of B.
      burgdorferi infection is complex and may be further confounded by the immune
      response to the recombinant outer surface protein A (OspA) Lyme disease vaccine.
      To describe how the serological response to the recombinant OspA Lyme disease
      vaccine affects testing for antibody to B. burgdorferi, 240 specimens from 80
      study subjects were obtained at defined intervals after recombinant OspA Lyme
      disease vaccination. Samples were tested by indirect enzyme-linked immunosorbent
      assay (ELISA), antibody capture enzyme immunoassay (EIA), and Western blotting
      (WB). After recombinant OspA Lyme disease vaccination, ELISA for 98% of the study
      subjects revealed reactivity. WB with use of OspA-containing B. burgdorferi
      strains as sources of antigens demonstrated multiple bands. Results of testing
      with a US Food and Drug Administration-approved WB kit showed homogeneous
      reactivity in the molecular weight region >30 kDa. Testing with OspA-free strains
      completely eliminated all vaccine-associated reactivity by both antibody capture
      EIA and WB.

PMID- 10913395
TI  - Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study.
AB  - We conducted this study to determine whether infection with human herpesvirus
      (HHV) 6A, HHV-6B, or HHV-7 differed between patients with chronic fatigue
      syndrome and control subjects. We recruited 26 patients and 52 nonfatigued
      matched control subjects from Atlanta. Serum samples were tested by enzyme
      immunoassay for seroreactivity to HHV-6, and all were seropositive. Lymphocyte
      specimens were cocultivated with cord blood lymphocytes and assayed for HHV-6 and
      HHV-7; neither virus was isolated. Finally, lymphocytes were tested by use of 3
      polymerase chain reaction methods for HHV-6A, HHV-6B, and HHV-7 DNA. HHV-6A or
      HHV-6B DNA was detected in 17 (22.4%) of 76 samples, and there were no
      significant differences (by matched analyses) between patients (3 [11.5%] of 26)
      and control subjects (14 [28%] of 50). HHV-7 DNA was detected in 14 subjects, and
      although control subjects (12 [24%]) were more likely than patients (2 [7.7%]) to
      be positive, the difference was not statistically significant. We found no
      evidence that active or latent infection with HHV-6A, HHV-6B, HHV-7, or any
      combination these 3 HHVs is associated with chronic fatigue syndrome.

PMID- 10913396
TI  - Bacterial meningitis in Malawian adults: pneumococcal disease is common, severe,
      and seasonal.
AB  - We prospectively collected laboratory details and outcome data on all patients
      with laboratory-confirmed cases of meningitis that presented to our unit in
      Blantyre, Malawi, from 1 April 1998 through 31 March 1999. There were 502
      patients with cases of meningitis; the most common causative organisms were
      Cryptococcus neoformans and Streptococcus pneumoniae. This pattern probably
      reflects the local human immunodeficiency virus (HIV) seroprevalence (31%) and is
      different from the pattern in 1974, when Neisseria meningitidis was the most
      common isolate. There has been an 8-fold increase in the number of meningitis
      cases per year since 1974, and a doubling of the percentage of medical admissions
      due to meningitis. The inpatient mortality rate among patients with cases of
      pneumococcal meningitis was 61%, and in the group as a whole was 41%. Despite the
      HIV-related pattern of infecting pathogens among these cases of meningitis and
      the increased incidence of the condition, there was evidence that the typical
      seasonal pattern of pneumococcal meningitis, which peaks in the cold, dry season,
      was preserved.

PMID- 10913397
TI  - Invasive pneumococcal infections in Canadian children, 1991-1998: implications
      for new vaccination strategies. Canadian Paediatric Society/Laboratory Centre for
      Disease Control Immunization Monitoring Program, Active (IMPACT).
AB  - We reviewed 2040 consecutive cases of invasive pneumococcal infection that were
      seen at 11 pediatric centers across Canada during 1991-1998 to determine if such
      infections could be prevented by new conjugate vaccines. Isolates from 1528 cases
      were serotyped. Most cases (61.5%) occurred in patients aged >2 years. Underlying
      medical conditions were present in 23.2% of case patients. Serotypes in the 7
      valent conjugate vaccine matched isolates as follows: 85.8% of tested isolates
      from children aged 6 months to 5 years, but significantly fewer isolates in
      younger and older children; 72.9% of isolates from non-healthy children, but
      83.9% of isolates from previously healthy children; and 95.4% of isolates with
      high-level penicillin resistance, but only 72.7% of those with intermediate-level
      resistance. Significant natural variation in the proportion of isolates matching
      7-valent vaccines occurred from year to year and among centers. New conjugate
      vaccines have great potential but their effectiveness and limitations require
      ongoing study.

PMID- 10913398
TI  - Human parvovirus B19 infection in infancy associated with acute and chronic
      lymphocytic myocarditis and high cytokine levels: report of 3 cases and review.
AB  - Human parvovirus B19 infection is occasionally associated with acute lymphocytic
      myocarditis (ALM). Three infants with B19 virus-associated ALM were followed up
      clinically, histologically, and immunovirologically. Each infant had B19 virus
      DNA in the blood or B19 virus-specific IgM antibodies. Two infants with postnatal
      infection recovered after immunosuppressive therapy. The third infant with
      possible prenatal infection developed chronic persistent myocarditis associated
      with persistent B19 virus DNA in the blood. All 3 infants had increased levels of
      interferon-gamma, tumor necrosis factor-alpha, and interleukins -6 and -8. Four
      newborns with congenital B19 virus infection and 4 infants and children who had
      postnatally acquired B19 virus infection without myocarditis all had normal
      levels of these cytokines. These observations suggest that B19 virus infection in
      infancy causes ALM in some infants and children.

PMID- 10913399
TI  - Tuberculous peritonitis in patients undergoing continuous ambulatory peritoneal
      dialysis: case report and review.
AB  - A case of tuberculous peritonitis complicating continuous ambulatory peritoneal
      dialysis (CAPD) in a 37-year-old man who presented with fever, abdominal pain,
      and a malfunctioning Tenckhoff catheter is reported. The patient was initially
      treated for presumed bacterial peritonitis but remained febrile and had
      persistent abdominal pain and peritoneal fluid pleocytosis, despite broad
      spectrum antibiotic therapy. Mycobacterium tuberculosis was isolated in a culture
      of peritoneal fluid, and the patient responded promptly to antituberculous
      therapy. More than 50 cases of tuberculous peritonitis complicating CAPD that
      have been reported in the English-language literature since the initial case was
      reported in 1980 are reviewed. The most common symptoms are fever (78%),
      abdominal pain (92%), and cloudy dialysate (90%); 76% of cases had a predominance
      of polymorphonuclear cells in peritoneal fluid. A smear for acid-fast bacilli or
      a culture was positive in 73% of cases. The peritoneal dialysis catheter was
      removed in 53% of cases, although this was rarely considered necessary for cure
      of tuberculosis. The attributable mortality rate is 15%, with the most
      significant factor being treatment delay (mean time from presentation to
      initiation of treatment, 6.74 weeks). We conclude that tuberculosis is an
      important diagnostic consideration for CAPD patients with peritonitis that is
      refractory to broad-spectrum antibiotics.

PMID- 10913400
TI  - Antibiotic susceptibility profiles for group B streptococci isolated from
      neonates, 1995-1998.
AB  - Antibiotic susceptibility profiles were analyzed for 119 invasive and 227
      colonizing strains of group B streptococci isolated from neonates at 6 US
      academic centers. All strains were susceptible to penicillin, vancomycin,
      chloramphenicol, and cefotaxime. The rate of resistance to erythromycin was 20.2%
      and to clindamycin was 6.9%. Resistance to erythromycin increased in 1997. Type V
      strains were more resistant to erythromycin than were type Ia (P=.003) and type
      Ib (P=.004) strains and were more resistant to clindamycin than were type Ia
      (P<.001), type Ib (P=.01), and type III (P=.001) strains. Resistance rates varied
      with geographic region: in California, there were high rates of resistance to
      erythromycin and clindamycin (32% and 12%, respectively), and low rates in
      Florida (8.5% and 2.1%, respectively). Penicillin continues to be the drug of
      choice for treatment of group B streptococcus infection. For women who are
      penicillin intolerant, however, the selection of an alternative antibiotic should
      be guided by contemporary resistance patterns observed in that region.

PMID- 10913401
TI  - Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during
      bacterial meningitis: association with blood-brain barrier damage and
      neurological sequelae.
AB  - To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in
      bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and
      endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in
      the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were
      detected in 91% and 97%, respectively, of CSF specimens from patients but were
      not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5
      patients who developed hearing impairment or secondary epilepsy than in those who
      recovered without neurological deficits. Levels of MMP-9 correlated with
      concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03).
      Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated
      independently and did not correlate with the CSF cell count. Therefore, MMPs may
      derive not only from granulocytes infiltrating the CSF space but also from
      parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a
      risk factor for the development of postmeningitidal neurological sequelae.

PMID- 10913402
TI  - Preparing for elimination of congenital Rubella syndrome (CRS): summary of a
      workshop on CRS elimination in the United States.
AB  - The goal of eliminating indigenous rubella and congenital rubella syndrome (CRS)
      in the United States in the near future is now within reach, because rubella
      incidence has been sustained at record-low levels since the mid-1990s. Effective
      prevention strategies to eliminate CRS and rubella require improvement in the
      surveillance of CRS and congenital rubella infection (CRI). The purpose of the
      workshop was to review rubella and CRS epidemiology, as well as current clinical,
      diagnostic, and laboratory practices, to determine whether new strategies are
      needed to achieve and document CRS elimination. Workshop participants agreed that
      surveillance for CRS must be strengthened, particularly through augmented
      laboratory capabilities, and the case definition for CRS must be revised to
      reflect the current scientific information available. Further studies of methods
      are needed to identify high-risk populations and geographic areas for rubella and
      CRS and to enhance identification of infants with CRS.

PMID- 10913403
TI  - Spectrum of clinical illness in hospitalized patients with "common cold" virus
      infections.
AB  - The viruses associated most frequently with the "common cold" are rhinoviruses
      and coronaviruses. The first prospective cohort study to determine the prevalence
      of rhinovirus and coronavirus infections in patients of all ages hospitalized for
      acute respiratory illnesses is described. Hospital admissions for acute
      respiratory illnesses were identified, and cell culture for rhinovirus and
      serologic assays on paired sera for coronaviruses 229E and OC43 were performed. A
      total of 61 infections with rhinoviruses and coronaviruses were identified from
      1198 respiratory illnesses (5.1%); in addition, 9 additional infections
      associated with >/=1 other respiratory viruses were identified. Of those infected
      with only rhinovirus or coronavirus, underlying cardiopulmonary diseases were
      present in 35% of the patients aged <5 years, in 93% aged between 5 and 35 years,
      and in 73% aged >35 years. The predominant clinical syndromes varied by age:
      pneumonia and bronchiolitis in children aged <5 years; exacerbations of asthma in
      older children and young adults; and pneumonia and exacerbations of chronic
      obstructive pulmonary disease and congestive heart failure in older adults.
      Therefore, rhinovirus and coronavirus infections in hospitalized patients were
      associated with lower respiratory tract illnesses in all age groups.

PMID- 10913404
TI  - Endemic carbapenem-resistant Acinetobacter species in Brooklyn, New York:
      citywide prevalence, interinstitutional spread, and relation to antibiotic usage.
AB  - Acinetobacter species are problematic nosocomial pathogens. In November 1997,
      pathogens isolated by microbiology laboratories were collected from 15 hospitals
      in Brooklyn, New York. Acinetobacter species accounted for 10% of gram-negative
      isolates. Only half of Acinetobacter species were susceptible to carbapenems; 11
      hospitals had at least 1 isolate resistant to carbapenems. Other Acinetobacter
      susceptibility rates were as follows: polymyxin, 99%; amikacin, 87%;
      ampicillin/sulbactam, 47%; ceftazidime, 25%; and ciprofloxacin 23%. Overall, 10%
      were resistant to all commonly used antibiotics. Genetic analysis by use of
      pulsed-field gel electrophoresis of 12 carbapenem-resistant isolates revealed 4
      strains that were recovered from >1 hospital, which suggests interinstitutional
      spread. Antibiotic usage data from 11 hospitals revealed that the use of third
      generation cephalosporins was associated significantly with the percentage of
      carbapenem-resistant strains (P=.03). Resistant Acinetobacter species have become
      endemic in Brooklyn, New York. Citywide strategies that involve surveillance,
      infection-control practices, and the reduction of antibiotic usage may be
      necessary to control the spread of these pathogens.

PMID- 10913405
TI  - Incidence and prevalence of recurrent respiratory papillomatosis among children
      in Atlanta and Seattle.
AB  - The incidence and prevalence of recurrent respiratory papillomatosis (RRP) for
      children aged <18 years were estimated in 2 US cities, Atlanta and Seattle, in
      1996. All otolaryngologists in a 24-county area in metropolitan Atlanta (101
      physicians) and an 8-county area in metropolitan Seattle (139 physicians) agreed
      to participate in the study. Medical record chart abstraction was performed only
      for children with documented current residence in the study area (21 patients in
      Atlanta and 14 patients in Seattle). The incidence rate for juvenile RRP was
      1.11/100,000 population in Atlanta and 0.36/100, 000 in Seattle. The prevalence
      rate was 2.59/100,000 population in Atlanta and 1.69/100,000 in Seattle. In
      neither city did prevalences differ significantly when stratified by sex or race.
      Extrapolation of these estimates to the US population suggests that 80-1500
      incident cases and 700-3000 prevalent cases of juvenile RRP will occur in the
      United States during 1999.

PMID- 10913406
TI  - Factors determining prevalence of maternal antibody to measles virus throughout
      infancy: a review.
AB  - The effectiveness of vaccination against measles, the leading cause of vaccine
      preventable deaths in infants globally, is greatly impacted by the level of
      maternal antibody to measles virus (or "measles maternal antibody"; MMA) during
      infancy. Variation in the prevalence of maternal antibody to measles virus
      between infant populations across countries and sociodemographic strata is poorly
      understood. We reviewed the literature on the prevalence of MMA, focusing on 3
      principal determinants: starting level of maternal antibody, placental transfer
      of maternal antibody, and rate of decay of maternal antibody after birth. Our
      review identified placental transfer as an important determinant, with greater
      efficiency found in studies performed in developed countries. Placental transfer
      was influenced by gestational age, human immunodeficiency virus infection, and
      malaria. Antibody levels in mothers varied widely between countries, although
      predictably according to vaccination status within populations. Rates of antibody
      decay across studies were similar. Future studies should evaluate the utility of
      the cord blood level of MMA as a predictor of vaccine efficacy in infancy;
      inclusion of World Health Organization international reference sera will
      facilitate comparisons. Greater understanding of the determinants of the
      prevalence of MMA will help national policy makers determine the appropriate age
      for measles vaccination.

PMID- 10913407
TI  - Treatment of latent tuberculosis infection: renewed opportunity for tuberculosis
      control.
AB  - New recommendations for targeted tuberculin testing and treatment of latent
      tuberculosis (TB) infection have recently been published. Changes in nomenclature
      from screening to targeted tuberculin testing and from preventive therapy to
      treatment of latent TB infection (LTBI) are intended to promote more widespread
      implementation by programs and health care providers. Targeted tuberculin testing
      is designed to identify persons at high risk for TB and is discouraged for
      persons at low risk. New recommendations for treatment of LTBI in both human
      immunodeficiency virus (HIV)-infected and HIV-uninfected patients include
      isoniazid for 9 months as the preferred regimen: isoniazid for 6 months based on
      local program conditions, rifampin and pyrazinamide for 2 months, and rifampin
      for 4 months. Treatment monitoring now places greater emphasis on clinical,
      rather than routine, laboratory monitoring. More widespread implementation of
      targeted tuberculin testing and treatment of LTBI is an important control
      strategy that will enhance efforts to eliminate TB in the United States.

PMID- 10913408
TI  - Special section: food safety.

PMID- 10913410
TI  - Bartonella quintana and urban trench fever.
AB  - Contemporary Bartonella quintana infections have emerged in diverse regions of
      the world, predominantly involving socially disadvantaged persons. Available data
      suggest that the human body louse Pediculus humanus is the vector for
      transmission of B. quintana. Descriptions of the clinical manifestations
      associated with contemporary B. quintana infections have varied considerably and
      include asymptomatic infection, a relapsing febrile illness, headache, leg pain,
      "culture-negative" endocarditis, and, in human immunodeficiency virus-infected
      persons, bacillary angiomatosis. Laboratory diagnosis is most convincing when B.
      quintana is isolated in blood culture, but growth often takes 20-40 days;
      problems exist with both sensitivity and specificity of serological assays. On
      the basis of available information, use of doxycycline, erythromycin, or
      azithromycin to treat B. quintana infections is recommended. Treatment of
      uncomplicated B. quintana bacteremia for 4-6 weeks and treatment of B. quintana
      endocarditis (in a person who does not undergo valve surgery) for 4-6 months are
      recommended, with the addition of a bactericidal agent (such as a third
      generation cephalosporin or an aminoglycoside) during the initial 2-3 weeks of
      therapy for endocarditis.

PMID- 10913409
TI  - Fluoroquinolone resistance in Salmonella: a web discussion.

PMID- 10913412
TI  - Dengue fever in international travelers.
AB  - Dengue virus infection is becoming increasingly recognized as one of the world's
      major emerging infectious diseases. Although only a few systematic studies have
      been conducted to assess the incidence and clinical course of dengue fever in
      travelers, it is now possible to estimate risk factors for travelers to areas of
      endemicity. Dengue virus and its vector, Aedes mosquitoes, benefit from human
      habitation and travel-related aspects of human behavior. Thus, travelers serve an
      important double role as potential victims of the disease and as vehicles for
      further spread of dengue.

PMID- 10913411
TI  - Replace hand washing with use of a waterless alcohol hand rub?
AB  - Hand hygiene is one of the basic components of any infection control program and
      is frequently considered synonymous with hand washing. However, health care
      workers frequently do not wash their hands, and compliance rarely exceeds 40%.
      Hand rubbing with a waterless, alcohol-based rub-in cleanser is commonly used in
      many European countries instead of hand washing. Scientific evidence and ease of
      use support employment of a hand rub for routine hand hygiene. It is
      microbiologically more effective in vitro and in vivo, it saves time, and
      preliminary data demonstrate better compliance than with hand washing. Therefore,
      a task force comprising experts from the Centers for Disease Control and
      Prevention and from professional societies is designing guidelines for the use of
      a hand rub in the United States. Today, most countries of Northern Europe
      recommend a hand rub for hand hygiene unless the hands are visibly soiled. Side
      effects are rare and are mainly related to dryness of the skin. This review
      evaluates the scientific and clinical evidence that support the use of alcohol
      based hand rubs in health care facilities as a new option for hand hygiene.

PMID- 10913413
TI  - Fever in the elderly.
AB  - Infections in the elderly, similar to other acute illnesses in this age group,
      may present in atypical, nonclassical fashions. Fever, the cardinal sign of
      infection, may be absent or blunted 20%-30% of the time. An absent or blunted
      fever response may in turn contribute to diagnostic delays in this population,
      which is already at risk for increased morbidity and mortality due to infection.
      On the other hand, the presence of a fever in the geriatric patient is more
      likely to be associated with a serious viral or bacterial infection than is fever
      in a younger patient. Finally, a diagnosis can be made in the majority of cases
      of fever of unknown origin (FUO) in the elderly. FUO is often associated with
      treatable conditions in this age group.

PMID- 10913414
TI  - Hepatitis C virus/human immunodeficiency virus coinfection: clinical management
      issues.
AB  - The use of highly active antiretroviral therapy (HAART) has extended the healthy
      lifespan of patients infected with human immunodeficiency virus (HIV); deaths
      among people with AIDS declined for the first time in 1996, after the institution
      of this therapeutic approach. As the life expectancy of HIV-infected patients
      increases, greater attention will need to be focused on the recognition and
      management of potentially severe concurrent illnesses that may increase their mid
      to long-range morbidity and mortality. The incidence of infection by hepatitis C
      virus (HCV) is increased among patients with HIV disease, reflecting shared
      epidemiological risks. HCV not only may have an impact on the health status of
      HIV-infected patients but also may decrease their quality of life and increase
      their health care costs. Although clinicians have been reluctant to treat viral
      hepatitis C in the HIV-infected population, this therapeutic nihilism is
      unwarranted. The majority of studies have concluded that treatment of hepatitis C
      in HIV-infected patients results in an initial efficacy and long-term response
      similar to those in the HIV-seronegative population. Furthermore, treatment of
      HCV infection in HCV/HIV-coinfected patients may improve tolerance for
      antiretroviral medications. Physicians caring for patients with HIV infection
      require up-to-date information to make rational decisions regarding HCV
      coinfection to ensure that morbidity and mortality are minimized and that quality
      of life and medical care costs are optimized.

PMID- 10913415
TI  - Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus
      infected patients receiving nucleoside analogue combination regimens.
AB  - During a 6-and-a-half month period, we identified 10 human immunodeficiency virus
      (HIV)-infected men who were receiving antiretroviral regimens, including
      nucleoside analogues, and who developed unexplained reproducible hyperlactatemia
      in association with either abdominal symptoms or an unaccounted-for elevated
      alanine aminotransferase level, or both. After careful consideration of the
      possible etiologies, antiretrovirals were discontinued; lactate levels normalized
      in all patients. The estimated incidence of this phenomenon in our clinic was
      20.9 cases per 1000 person-years of nucleoside analogue treatment. These
      observations extend the spectrum of the nucleoside analogue-induced lactic
      acidosis/hepatic steatosis syndrome by the identification of a subtle and perhaps
      earlier form, which has characteristic symptoms and laboratory abnormalities, and
      a favorable prognosis on discontinuation of antiretroviral therapy.

PMID- 10913416
TI  - Editorial response: hyperlactatemia and hepatic steatosis as features of
      mitochondrial toxicity of nucleoside analogue reverse transcriptase inhibitors.

PMID- 10913417
TI  - Increased disease burden and antibiotic resistance of bacteria causing severe
      community-acquired lower respiratory tract infections in human immunodeficiency
      virus type 1-infected children.
AB  - To improve the management of lower respiratory tract infections (LRTI) in human
      immunodeficiency virus type 1 (HIV-1)-infected children, we assessed the burden
      of disease, clinical outcome and antibiotic susceptibility of bacteria causing
      severe community-acquired LRTI in children. A prospective, descriptive study was
      performed in the pediatric wards at a secondary and tertiary care hospital in
      South Africa. Urban black children aged 2-60 months admitted with severe acute
      LRTI from March 1997 through February 1998 were enrolled. HIV-1 infection was
      present in 45.1% of 1215 cases of severe LRTI. Bacteremia occurred in 14.9% of
      HIV-1-infected and in 6.5% of HIV-1-uninfected children (P<.00001). The estimated
      relative incidence of bacteremic severe LRTI in children aged from 2 to 24 months
      were greater in HIV-1-infected than in -uninfected children for Streptococcus
      pneumoniae (risk ratio [RR], 42.9; 95% confidence interval [CI], 20.7-90.2),
      Haemophilus influenzae type b (RR, 21.4; 95% CI, 9.4-48.4), Staphylococcus aureus
      (RR, 97.9; 95% CI, 11.4-838.2) and Escherichia coli (RR, 49.0; 95% CI, 15.4-156).
      Isolation of Mycobacterium tuberculosis was also more common in HIV-1-infected
      than in -uninfected children (RR, 22.5; 95% CI, 13.4-37.6). In HIV-1-infected
      children, 60% of S. aureus and 85.7% of E. coli isolates were resistant to
      methicillin and trimethoprim-sulfamethoxazole, respectively. The case-fatality
      rates among HIV-1-infected children was 13.1%, and among HIV-1-uninfected
      children, 2.1% (adjusted odds ratio [AOR]; 6.52, 95% CI, 3.53-12.05; P<.00001).
      The changing spectrum of bacteria and antibiotic susceptibility patterns in HIV-1
      infected children requires a reevaluation of the empirical treatment of community
      acquired severe LRTI in children from developing countries with a high prevalence
      of childhood HIV-1 infection.

PMID- 10913418
TI  - Brief report: disseminated mycobacteriosis caused by drug-resistant Mycobacterium
      triplex in a human immunodeficiency virus-infected patient during highly active
      antiretroviral therapy.
AB  - Mycobacterium triplex is a novel species that, until now, has been isolated only
      from limited clinical samples, and its clinical relevance has been largely
      unknown. In this report, we describe the first case of disseminated disease
      caused by M. triplex in a human immunodeficiency virus-infected patient.

PMID- 10913419
TI  - Severe Chlamydia pneumoniae infection in patients with neutropenia: case reports
      and literature review.
AB  - Three cases of life-threatening C. pneumoniae infection in patients with acute
      leukemia and treatment-induced neutropenia are described. Diagnosis was made on
      the basis of the detection of C. pneumoniae-DNA, complemented by serology. The
      role of the widely distributed respiratory tract pathogen C. pneumoniae in
      febrile neutropenia is poorly understood, and studies are needed to estimate the
      frequency of severe pulmonary infection caused by this agent in patients with
      neutropenia.

PMID- 10913421
TI  - Significance of aspergillemia in patients with cancer: a 10-year study.
AB  - The significance of blood cultures positive for Aspergillus species for patients
      with cancer remains unclear. The significance of aspergillemia in 36 cancer
      patients over a 10-year period was evaluated. True aspergillemia was rare,
      occurred late in the course of aspergillosis, and was seen exclusively in
      patients with hematologic malignancies.

PMID- 10913420
TI  - Molecular evidence of ocular Epstein-Barr virus infection.
AB  - Ocular manifestations have been attributed to the Epstein-Barr virus (EBV),
      largely on the basis of seroepidemiologic data. Two patients who developed
      conjunctival disease as the presenting feature of EBV infection are reported,
      each confirmed by in situ hybridization of EBV genome in affected tissue biopsy
      specimens. Recognition of EBV-induced ocular disease as an initial presentation
      of clinical EBV infection is important to the practitioner because of the
      ubiquitous nature of this herpesvirus.

PMID- 10913422
TI  - Two unusual presentations of urogenital histoplasmosis and a review of the
      literature.
AB  - Two unusual clinical presentations of urogenital histoplasmosis are described. A
      review of the literature on urogenital histoplasmosis is provided.

PMID- 10913423
TI  - Multiple organ failure complicating probable scrub typhus.
AB  - This report describes a case of life-threatening acute respiratory distress
      syndrome with multiple organ failure complicating probable scrub typhus.
      Favorable outcome was associated with fluoroquinolone therapy. Scrub typhus
      should be suspected in travelers returning from Southeast Asia presenting with
      unexplained respiratory manifestations.

PMID- 10913424
TI  - Acute community-acquired diarrhea requiring hospital admission in Swiss children.
AB  - In order to ascertain the prevalence of agents that cause childhood diarrheal
      illness, stool specimens of 312 consecutive children with community-acquired
      diarrhea requiring admission were evaluated. Pathogens were detected in 166 (53%)
      of the 312 children (>/=2 pathogens in 28 children): Rotavirus (n=75), Salmonella
      spp. (n=37), Campylobacter spp. (n=24), Shigella spp. (n=5), Giardia spp. (n=4),
      Yersinia spp. (n=2), Aeromonas spp. (n=15), Cryptosporidium (n=15),
      enteropathogenic Escherichia coli (n=13), enterotoxigenic E. coli (n=7), and
      enterohemorrhagic E. coli (n=5). In conclusion, acute childhood diarrheal illness
      pathogens, such as Aeromonas, Cryptosporidium, and diarrheagenic E. coli, account
      for a large proportion of patients with a microbiologically positive stool
      specimen.

PMID- 10913425
TI  - Rapid progressive subacute sclerosing panencephalitis in a 2-year-old child with
      congenital athyreosis.
AB  - We present the unique case of a 2-year-old girl with congenital athyreosis who
      acquired primary measles virus infection at the age of 18 months, coincidentally
      with an Epstein-Barr virus infection. First neurologic symptoms of subacute
      sclerosing panencephalitis appeared 5 months later, and the girl died within 6
      months after a rapid progressive illness. Factors possibly predisposing to this
      extraordinary disease course-primary measles virus infection at an early age and
      lack of evidence for immunodeficiency-are discussed.

PMID- 10913426
TI  - Cutaneous leishmaniasis following local trauma: a clinical pearl.
AB  - Cutaneous leishmaniasis is acquired from the bite of an infected sand fly and can
      result in chronic skin lesions that develop within weeks to months after a bite.
      Local trauma has been implicated as a precipitating event in the development of
      skin lesions in patients who have been infected with Leishmania species. Here we
      report a case series and review the literature on patients who developed
      cutaneous leishmaniasis after local trauma, which may familiarize clinicians with
      this presentation.

PMID- 10913427
TI  - Helicobacter cinaedi septic arthritis and bacteremia in an immunocompetent
      patient.
AB  - We report on the first case of documented Helicobacter cinaedi septic arthritis
      in an immunocompetent heterosexual young man. The patient presented no identified
      risk factor except for contact with animals that have been incriminated as a
      possible source of infection, particularly for these patients. Despite prolonged
      bacteremia, the response to long-term therapy with ciprofloxacin and rifampin was
      excellent.

PMID- 10913428
TI  - Report of successful prolonged antifungal therapy for refractory allergic fungal
      sinusitis.
AB  - Allergic fungal sinusitis (AFS) is an increasingly recognized cause of refractory
      chronic sinusitis in the young immunocompetent host, analogous to allergic
      bronchopulmonary aspergillosis (ABPA), a related process in the lower respiratory
      tract. Most patients experience remittent disease despite corticosteroid therapy
      and aggressive sinus surgery. Because controlled trials have shown adjunctive
      antifungal therapy to be of benefit in treating ABPA, long-term oral itraconazole
      was used in a young man with remittent AFS, which was able to break the cycle of
      relapsing disease.

PMID- 10913429
TI  - Are "old" pioneering papers Passe?

PMID- 10913430
TI  - Reply

PMID- 10913431
TI  - Follow-up in herpes simplex virus encephalitis.

PMID- 10913432
TI  - Hyperlipidemia associated with the use of protease inhibitors.

PMID- 10913433
TI  - Successful treatment of vertebral osteomyelitis with linezolid in a patient
      receiving hemodialysis and with persistent methicillin-resistant Staphylococcus
      aureus and vancomycin-resistant Enterococcus bacteremias.

PMID- 10913434
TI  - The final nail.

PMID- 10913435
TI  - Analysis of plus-strand primer selection, removal, and reutilization by
      retroviral reverse transcriptases.
AB  - The ability of reverse transcriptase to generate, extend, and remove the primer
      derived from the polypurine tract (PPT) is vital for reverse transcription, since
      this process determines one of the ends required for integration of the viral
      DNA. Based on the ability of the RNase H activity of Moloney murine leukemia
      virus reverse transcriptase to cleave a long RNA/DNA hybrid containing the PPT,
      it appears that cleavages that could generate the plus-strand primer can occur by
      an internal cleavage mechanism without any positioning by an RNA 5'-end, and such
      cleavages may serve to minimize cleavage events within the PPT itself. If the PPT
      were to be cleaved inappropriately just upstream of the normal plus-strand origin
      site, the resulting 3'-ends would not be extended by reverse transcriptase.
      Extension of the PPT primer by at least 2 nucleotides is sufficient for
      recognition and correct cleavage by RNase H at the RNA-DNA junction to remove the
      primer. Specific removal of the PPT primer after polymerase extension deviates
      from the general observation that primer removal occurs by cleavage one
      nucleotide away from the RNA-DNA junction and suggests that the same PPT
      specificity determinants responsible for generation of the PPT primer also direct
      PPT primer removal. Once the PPT primer has been extended and removed from the
      nascent plus-strand DNA, reinitiation at the resulting plus-strand primer
      terminus does not occur, providing a mechanism to prevent the repeated initiation
      of plus strands.

PMID- 10913436
TI  - La autoantigen is cleaved in the COOH terminus and loses the nuclear localization
      signal during apoptosis.
AB  - La autoantigen is a 47-kDa nuclear protein that binds to nascent polymerase III
      transcripts and a number of viral RNAs. We show that La protein was cleaved to
      generate a 43-kDa fragment during apoptosis of human leukemic HL-60 cells treated
      with camptothecin or etoposide. Immunofluorescence microscopy showed that the La
      protein level was increased in the cytoplasm during apoptosis of HL-60 cells. In
      addition, UV irradiation of HeLa cells led to the cleavage and redistribution of
      La protein upon apoptosis. Several lines of evidence show that La protein is
      cleaved by caspase-3 or closely related proteases at Asp-374 in the COOH
      terminus. When the full-length (La) and COOH-terminally truncated (La delta C374)
      forms of La protein were expressed as fusion proteins with green fluorescence
      protein (GFP), GFP-La delta C374 was predominantly cytoplasmic, whereas GFP-La
      was localized in the nucleus. These results suggest that La protein loses the
      nuclear localization signal residing in the COOH terminus upon cleavage and is
      thus redistributed to the cytoplasm during apoptosis.

PMID- 10913437
TI  - Effects of site-directed mutagenesis on structure and function of recombinant rat
      liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme.
AB  - A site-directed mutagenesis, D244E, of S-adenosylhomocysteine hydrolase
      (AdoHcyase) changes drastically the nature of the protein, especially the NAD(+)
      binding affinity. The mutant enzyme contained NADH rather than NAD(+) (Gomi, T.,
      Takata, Y., Date, T., Fujioka, M., Aksamit, R. R., Backlund, P. S., and Cantoni,
      G. L. (1990) J. Biol. Chem. 265, 16102-16107). In contrast to the site-directed
      mutagenesis study, the crystal structures of human and rat AdoHcyase recently
      determined have shown that the carboxyl group of Asp-244 points in a direction
      opposite to the bound NAD molecule and does not participate in any hydrogen bonds
      with the NAD molecule. To explain the discrepancy between the mutagenesis study
      and the x-ray studies, we have determined the crystal structure of the
      recombinant rat-liver D244E mutant enzyme to 2.8-A resolution. The D244E mutation
      changes the enzyme structure from the open to the closed conformation by means of
      a approximately 17 degrees rotation of the individual catalytic domains around
      the molecular hinge sections. The D244E mutation shifts the catalytic reaction
      from a reversible to an irreversible fashion. The large affinity difference
      between NAD(+) and NADH is mainly due to the enzyme conformation, but not to the
      binding-site geometry; an NAD(+) in the open conformation is readily released
      from the enzyme, whereas an NADH in the closed conformation is trapped and cannot
      leave the enzyme. A catalytic mechanism of AdoHcyase has been proposed on the
      basis of the crystal structures of the wild-type and D244E enzymes.

PMID- 10913439
TI  - Hsp90 chaperone activity requires the full-length protein and interaction among
      its multiple domains.
AB  - Hsp90 is an abundant and ubiquitous protein involved in a diverse array of
      cellular processes. Mechanistically we understand little of the apparently
      complex interactions of this molecular chaperone. Recently, progress has been
      made in assigning some of the known functions of hsp90, such as nucleotide
      binding and peptide binding, to particular domains within the protein. We used
      fragments of hsp90 and chimeric proteins containing functional domains from hsp90
      or its mitochondrial homolog, TRAP1, to study the requirements for this protein
      in the folding of firefly luciferase as well as in the prevention of citrate
      synthase aggregation. In agreement with others who have found peptide binding and
      limited chaperone ability in fragments of hsp90, we see that multiple fragments
      from hsp90 can prevent the aggregation of thermally denatured citrate synthase, a
      measure of passive chaperoning activity. However, in contrast to these results,
      the luciferase folding assay was found to be much more demanding. Here, folding
      is mediated by hsp70 and hsp40, requires ATP, and thus is a measure of active
      chaperoning. Hsp90 and the co-chaperone, Hop, enhance this process. This hsp90
      activity was only observed using full-length hsp90 indicating that the
      cooperation of multiple functional domains is essential for active, chaperone
      mediated folding.

PMID- 10913438
TI  - A role for nuclear phospholipase Cbeta 1 in cell cycle control.
AB  - Phosphoinositide signaling resides in the nucleus, and among the enzymes of the
      cycle, phospholipase C (PLC) appears as the key element both in Saccharomyces
      cerevisiae and in mammalian cells. The yeast PLC pathway produces multiple
      inositol polyphosphates that modulate distinct nuclear processes. The mammalian
      PLCbeta(1), which localizes in the nucleus, is activated in insulin-like growth
      factor 1-mediated mitogenesis and undergoes down-regulation during murine
      erythroleukemia differentiation. PLCbeta(1) exists as two polypeptides of 150 and
      140 kDa generated from a single gene by alternative RNA splicing, both of them
      containing in the COOH-terminal tail a cluster of lysine residues responsible for
      nuclear localization. These clues prompted us to try to establish the critical
      nuclear target(s) of PLCbeta(1) subtypes in the control of cell cycle
      progression. The results reveal that the two subtypes of PLCbeta(1) that localize
      in the nucleus induce cell cycle progression in Friend erythroleukemia cells. In
      fact when they are overexpressed in the nucleus, cyclin D3, along with its kinase
      (cdk4) but not cyclin E is overexpressed even though cells are serum-starved. As
      a consequence of this enforced expression, retinoblastoma protein is
      phosphorylated and E2F-1 transcription factor is activated as well. On the whole
      the results reveal a direct effect of nuclear PLCbeta(1) signaling in G(1)
      progression by means of a specific target, i.e. cyclin D3/cdk4.

PMID- 10913440
TI  - Discrimination between translesion synthesis and template switching during bypass
      replication of thymine dimers in duplex DNA.
AB  - The goal of this study was to determine whether bypass replication occurs by
      translesion synthesis or template switching (copy choice) when a duplex molecule
      carrying a single cis,syn-cyclobutane thymine dimer is replicated in vitro by
      human cell extracts. Circular heteroduplex DNA molecules were constructed to
      contain the SV40 origin of replication and a mismatch opposite to or nearby the
      dimer. Control molecules with only the mismatch were also prepared.
      Heteroduplexes were methylated at CpG islands and replicated in vitro (30 min).
      Following bisulfite treatment, the nascent DNA complementary to the dimer
      containing template was distinguished from the other three strands by methylation
      specific polymerase chain reaction. Cloning and sequencing of polymerase chain
      reaction products revealed that 80-98% carried the sequence predicted for
      translesion synthesis, with two adenines incorporated opposite the dimer. The
      fraction of clones with sequence predictive of template switching was reduced
      when extracts deficient in mismatch repair or nucleotide excision repair
      activities were used to replicate the heteroduplex molecules. These results
      support the conclusion that lesion bypass during in vitro replication of duplex
      DNA containing thymine dimers occurs by translesion synthesis.

PMID- 10913442
TI  - The changing face of chronic care.

PMID- 10913441
TI  - Kinectin-kinesin binding domains and their effects on organelle motility.
AB  - Intracellular organelle motility involves motor proteins that move along
      microtubules or actin filaments. One of these motor proteins, kinesin, was
      proposed to bind to kinectin on membrane organelles during movement. Whether
      kinectin is the kinesin receptor on organelles with a role in organelle motility
      has been controversial. We have characterized the sites of interaction between
      human kinectin and conventional kinesin using in vivo and in vitro assays. The
      kinectin-binding domain on the kinesin tail partially overlaps its head-binding
      domain and the myosin-Va binding domain. The kinesin-binding domain on kinectin
      resides near the COOH terminus and enhances the microtubule-stimulated kinesin
      ATPase activity, and the overexpression of the kinectin-kinesin binding domains
      inhibited kinesin-dependent organelle motility in vivo. These data, when combined
      with other studies, suggest a role for kinectin in organelle motility.

PMID- 10913444
TI  - An update on changes in salaries of psychologists in independent practice.

PMID- 10913446
TI  - Implementing best-practice guidelines for schizophrenia in a public-sector
      institution.

PMID- 10913447
TI  - Self-help treatment for combined addiction and mental illness.

PMID- 10913448
TI  - The humiliation of a psychiatry patient when she is a medical patient.

PMID- 10913449
TI  - Galactorrhea and gynecomastia in a hypothyroid male being treated with
      risperidone.

PMID- 10913450
TI  - The young adult chronic patient: overview of a population. 1981.

PMID- 10913451
TI  - The young adult chronic patient: a look back.

PMID- 10913452
TI  - Psychiatric residency training, managed care, and contemporary clinical practice.
AB  - Managed care has transformed the health care environment that residents encounter
      on completion of their training. Unfortunately, residency education has not kept
      pace with changes in the field, leaving graduates inadequately prepared. The
      authors identify necessary changes in the residency training tasks of instilling
      values, imparting required knowledge, building core skills, selecting appropriate
      training sites, and offering a diversity of instructors and supervisors. They
      also discuss the obstacles that have impeded the evolution of academic clinical
      services and clinical training. They suggest strategies of change that may lead
      to more relevant educational programs that provide residents with a balanced
      perspective on the strengths and weaknesses of both traditional and contemporary
      approaches to delivering care.

PMID- 10913453
TI  - Releasing information to families of persons with severe mental illness: a survey
      of NAMI members.
AB  - OBJECTIVE: Guidelines for the treatment of severe mental illness recommend that
      providers share information with families and involve them in treatment. However,
      research indicates that consumer-provider-family collaboration is not part of
      routine clinical practice. This study examined the process of releasing
      information to families and the types of information they receive. METHODS: Self
      administered surveys were completed by 219 family and consumer members of the
      National Alliance for the Mentally Ill. The surveys gathered information about
      their experiences with providers' releasing information. Consumers' attitudes
      toward collaboration and family members' satisfaction with providers were also
      measured. Regression analyses examined the relationship between consumers'
      attitudes toward family involvement and whether providers discussed family
      involvement or the release of information with consumers. Further analyses
      examined the relationship between family satisfaction and release of information.
      RESULTS: The majority of family respondents (72 percent) reported that they
      received some specific information about their relative's mental illness. Most
      families received information about diagnosis and medications, but few received
      information about the treatment plan. Few consumers reported that their
      permission was requested to release information to their families. Consumers'
      attitudes toward their family and toward family involvement were significantly
      associated with whether they were encouraged by their provider to involve a
      family member in their treatment. No significant relationship was found between
      consumers' attitudes and whether their provider discussed the release of
      information. Family members' satisfaction was positively related to whether they
      received information from providers. CONCLUSIONS: The findings suggest that
      although some information is shared with families, collaboration is not currently
      part of routine clinical practice.

PMID- 10913454
TI  - Homelessness among persons with serious mental illness in an enhanced community
      based mental health system.
AB  - OBJECTIVE: Homelessness and patterns of service use were examined among seriously
      mentally ill persons in an area with a well-funded community-based mental health
      system. METHODS: The sample consisted of 438 individuals referred between 1990
      and 1992 to an extended acute care psychiatric hospital after a stay in a general
      hospital. Those experiencing an episode of homelessness, defined as an admission
      to a public shelter between 1990 and 1993, were compared with those who were
      residentially stable. Data from a longitudinal integrated database of public
      mental health and medical services were used to construct service utilization
      measures to test the mediating effect of outpatient mental health care on
      preventing homelessness. RESULTS: A homelessness rate of 24 percent was found
      among the 438 persons with serious mental illness. Those who experienced
      homelessness were more likely to be African American, receive general assistance,
      and have a comorbid substance abuse problem. They used significantly more
      inpatient psychiatric, emergency, and health care services than the subjects who
      did not become homeless. Forty to 50 percent of the homeless group received
      outpatient care during the year before and after their shelter episode. The
      number of persons who received intensive case management services increased after
      shelter admission. CONCLUSIONS: An enhanced community-based mental health system
      was not sufficient to prevent homelessness among high-risk persons with serious
      mental illness. Eleven percent of this group experienced homelessness after
      referral to an extended acute care facility. Strategies to prevent homelessness
      should be considered, perhaps at the time of discharge from the referring
      community hospital or extended acute care facility.

PMID- 10913455
TI  - Referral and housing processes in a long-term supported housing program for
      homeless veterans.
AB  - OBJECTIVE: The study examined client characteristics, case management variables,
      and housing features associated with referral, entry, and short-term success in a
      Department of Veterans Affairs (VA) national intensive case management and rental
      assistance program for homeless veterans. METHODS: Information collected from
      homeless veterans at the time of initial outreach contact and from case managers
      during the housing search was used to create logistic regression models of
      referral into the program and successful completion of several stages in the
      process of obtaining stable independent housing. RESULTS: Overall, only 8 percent
      of the more than 65,000 eligible veterans contacted by outreach workers were
      referred to the program. Those referred were more likely to be female, to have
      more sources of income, to have recently used VA services (including residential
      treatment), and to have serious mental health problems. Once in the program, 64
      percent of veterans eventually moved into an apartment, and 84 percent of those
      who obtained an apartment were stably housed one year later. In general,
      activities of case managers, such as accompanying the veteran to the public
      housing authority and securing additional sources of income, were associated with
      success in the housing process. The therapeutic alliance, clients' housing
      preferences, and the quality of housing were unrelated to retention of housing.
      CONCLUSIONS: This supported housing program was judged appropriate for a small
      percentage of eligible veterans. However, a large proportion of clients were
      successful in attaining permanent housing, which lends support to the
      effectiveness of the supported housing approach.

PMID- 10913456
TI  - Factors predicting choice of provider among homeless veterans with mental
      illness.
AB  - OBJECTIVE: Homeless persons with serious mental illness are especially likely to
      lack access to comprehensive medical and psychiatric care. This study examined
      the relative importance of predisposing factors, illness factors, and enabling
      factors as determinants of the use of Veterans Affairs (VA) health care services
      by mentally ill homeless veterans seeking services from a non-VA program.
      Predisposing factors included demographic characteristics and wartime service;
      illness factors were related to the type of medical problem and the need to seek
      medical care; and enabling factors included entitlement to VA medical services
      and location of VA facilities. METHODS: Logistic regression analysis was used to
      analyze data for 698 homeless veterans with mental illness who were enrolled in
      the Access to Community Care and Effective Services and Supports (ACCESS)
      program. RESULTS: About 56 percent of the mentally ill homeless veterans had used
      VA services at some time in their lives. Homeless veterans were almost twice as
      likely as other poor veterans to use VA services; those with a dual diagnosis
      were also more likely to use VA services. Enabling factors were more important
      than either predisposing or illness factors in predicting VA service use.
      Veterans most likely to use VA services were those who received VA benefits that
      gave them priority access to VA services and those who lived near a VA medical
      center. CONCLUSIONS: Specific characteristics of the service system and of
      veterans' entitlement were more important than clinical needs or predisposing
      factors in predicting service use.

PMID- 10913457
TI  - Efficacy of continuing advocacy in involuntary treatment.
AB  - OBJECTIVE: The effectiveness of an experimental model of personal advocacy for
      involuntarily hospitalized psychiatric patients was examined. In the model, a
      personal advocate represented the needs and best interests of patients throughout
      the period of involuntary hospital treatment. METHODS: The sample consisted of
      105 involuntarily hospitalized psychiatric inpatients in Canberra, Australia.
      Fifty-three consecutive patients received personal advocacy, which started soon
      after they entered the hospital and lasted through the commitment process to the
      time of discharge from involuntary care. The outcome of this group was compared
      with that of 52 consecutive patients in a control group who received routine
      rights advocacy from hospital entry through the commitment hearing only. RESULTS:
      The experimental and control groups were similar in demographic characteristics,
      diagnosis, and severity of illness. At the start of hospital care, satisfaction
      with care was similar in both groups; however, it improved significantly in the
      experimental group while it declined in the control group. Aftercare attendance
      was significantly better in the experimental group. The experimental subjects'
      risk of involuntary rehospitalization was less than half the risk of control
      subjects, and community tenure was significantly increased. Clinical staff
      reported that the experimental advocacy facilitated management of patients.
      CONCLUSIONS: Compared with routine rights advocacy, the experimental advocacy
      based on patients' needs and best interests, which was maintained throughout the
      patients' involuntary hospitalization, significantly improved patients' and staff
      members' experience of involuntary treatment. Better compliance with aftercare
      among patients receiving personal advocacy led to a statistically and
      economically significant reduction in rehospitalization.

PMID- 10913458
TI  - Satisfaction of caregivers of patients with schizophrenia in Finland.
AB  - OBJECTIVE: The aims of the study were to determine whether the caregivers of
      discharged patients with schizophrenia were satisfied with their situation in
      general and with psychiatric services in particular and to examine the factors
      associated with caregiver satisfaction. METHODS: The data were drawn from a
      national project designed to study the treatment and life situation of
      deinstitutionalized schizophrenia patients in Finland. The patients were
      discharged from psychiatric hospitals in 1986, and both the patients (N=775) and
      their caregivers (N=545) were interviewed after a three-year follow-up. RESULTS:
      One-fifth of the caregivers were dissatisfied with the situation in general, and
      one-third were dissatisfied with the psychiatric services the patient received.
      Caregivers were more likely to be dissatisfied with the situation if they lived
      with the patient and if the patient's functional state was poor or the patient's
      use of services, particularly medication and rehabilitation, was low. Caregivers
      were likely to be dissatisfied with the psychiatric services if the patient had
      severe psychotic symptoms and poor "maintenance of grip on life" or if the
      patient was given less psychiatric care and rehabilitation or used more social
      services. CONCLUSIONS: The satisfaction of caregivers of persons with mental
      illness appears to have two dimensions. First, caregivers need to be accepted and
      treated as active partners in the patients' care and rehabilitation. Second, the
      burden on the families of persons with mental illness can be alleviated with long
      term rehabilitation and care to help patients gain as high a functional state as
      possible.

PMID- 10913459
TI  - Monitoring aggression and problem behaviors in inpatient neuropsychiatric units.
AB  - The Problem Behavior Recording System (PBRS) is a computer-based monitoring
      system for tracking aggression and other problem behaviors among inpatients on
      neuropsychiatric units. The authors describe the system and compare it with other
      tracking systems. In 1997 a total of 405 aggressive incidents on an aggressive
      ambulatory neuropsychiatry unit were recorded on the PBRS, whereas only 112
      incidents, or 28 percent, were documented in hospital incident reports. In a
      further analysis, nursing notes in the charts of three patients were examined for
      a three-month period; 34 aggressive incidents were documented, compared with 41
      PBRS entries for the same patients. The chart review took nearly three hours to
      complete, compared with less than five minutes for the PBRS analysis.

PMID- 10913460
TI  - A questionnaire to measure factors that protect youth against stressors of inner
      city life.
AB  - This study reports the development of the My Life Questionnaire (MLQ), a self
      report measure of factors that protect inner-city youth against stressors such as
      poverty, crime, and violence. An initial pool of 23 items reflecting important
      protective factors was developed through focus groups with inner-city youth and
      clinicians working with them in a school-based mental health program. Item-total
      correlations and factor analysis resulted in a 12-item measure containing three
      factors: avoiding negative peer influences, focusing on the future, and religious
      involvement. Scores on the MLQ were negatively correlated with behavioral
      problems, supporting its validity. The measure holds promise for use in clinical
      and research efforts with disadvantaged urban youth.

PMID- 10913461
TI  - Unmet needs for substance abuse and mental health services among Northern Plains
      American Indian adolescents.
AB  - Use of mental health and substance abuse services was examined among 109 American
      Indian adolescents in a Northern Plains reservation community. Each was
      interviewed to assess psychiatric diagnosis and service use and to determine
      whether an adult had recognized a problem in the adolescent-a critical
      determinant of receipt of services. Of the 23 youths who had a disorder, nine (39
      percent) reported lifetime service use. Of the 25 who received services, 17 were
      treated by a school counselor; only one received services from a mental health
      specialist. Eight of the 25 youths with a psychiatric or substance use diagnosis
      who did not receive services reported that an adult had recognized a problem.

PMID- 10913462
TI  - Jay Haley revisited: the art of being a failure as an administrator.

PMID- 10913464
TI  - Managed care in Iowa.

PMID- 10913466
TI  - Medicare's mental health coverage

PMID- 10913465
TI  - Medicare's mental health coverage.

PMID- 10913467
TI  - The newer antidepressants.

PMID- 10913468
TI  - Oral self-mutilation.

PMID- 10913469
TI  - The Jerusalem syndrome.

PMID- 10913470
TI  - Usefulness of topography of coronary calcium by electron-beam computed tomography
      in predicting the natural history of coronary atherosclerosis.
AB  - Electron-beam computed tomography (EBCT) allows for accurate noninvasive
      detection and quantification of coronary calcium that is representative of
      underlying atherosclerotic disease. The present study quantitatively analyzes the
      topography and establishes the natural history of coronary calcium in patients
      with variable degrees of coronary atherosclerosis. EBCT was performed in 330
      consecutive patients aged 56 +/- 12 years (70% men) with recent (<3 months) onset
      of signs or symptoms of coronary artery disease (CAD) or who were evaluated
      because of a presumed high risk. Total calcium scores, computed by the Agatston
      method, were positive in 269 patients (82%) (mean age 58 +/- 11 years, 73% men).
      These patients were classified into 4 groups, with total calcium scores ranging
      between 1 and 30, >30 and 100, >100 and 400, and >400, respectively. The presence
      and amount of calcium was additionally assessed in 10 major segments of the
      coronary arterial tree, including the major coronary arteries. Of the 72 patients
      with calcium of only 1 of the major coronary arteries, the left anterior
      descending coronary artery was involved in 39 patients (54%) and the right
      coronary artery in 18 patients (25%). Left main stem calcium was observed in only
      10 of 139 patients (7%) with 1- or 2-vessel calcium and in 17 of 77 patients
      (23%) with 3-vessel calcium. Calcium was consistent most frequently in the
      proximal left anterior descending coronary artery, followed by the proximal left
      circumflex and right coronary artery segments. A significant decrease of
      frequency and amount of calcium from the proximal to distal segments was observed
      in the left coronary system but not in the right coronary artery, where the
      distribution was more even. With increasing total calcium scores, segmental
      scores in the more distal segments were enhanced, but the increase was most
      pronounced in the proximal segments and particularly in the proximal left
      anterior descending coronary artery. EBCT-derived coronary calcium shows an axial
      distribution that appears comparable to that of atherosclerotic lesions observed
      in pathologic and angiographic studies, highlighting the potential role of EBCT
      for studying the natural history of CAD.

PMID- 10913471
TI  - Management of coronary risk factors by registered nurses versus usual care in
      patients with unstable angina pectoris (a chest pain evaluation in the emergency
      room [CHEER] substudy).
AB  - This study examined whether nurses could manage coronary risk factors in patients
      with unstable angina more effectively than physicians practicing usual care.
      Three hundred twenty-six patients were randomized in the emergency room to a 6
      month program of risk factor management by a registered nurse versus
      participation in usual care. The nurse intervention consisted of a 30-minute
      counseling visit at 6 to 10 days after the chest pain episode and a second 30
      minute session 1 month later. Multiple risk factors were assessed and addressed:
      smoking, blood lipids, blood pressure, blood glucose, physical inactivity,
      weight, psychological stress, and social isolation. Compared with usual care,
      nurse intervention patients significantly reduced both triglycerides (-29 +/- 8
      vs 5 +/- 6 mg/dl; p <0.0004) and weight (-0.9 +/- 3.3 vs +0.1 +/- 2.1 kg; p =
      0.0071), and had corresponding improvements in self-reported diet compliance and
      exercise (+34 +/- 106 vs +9 +/- 98 minutes, p = 0.0491). No significant
      differences between groups were observed in terms of 6-month changes in total,
      high-density lipoprotein, or low-density lipoprotein cholesterol, blood pressure,
      fasting blood glucose, percent body fat or waist-hip ratio, or psychological
      distress scores. The 6-month rate of recurrent events (cardiac death, out-of
      hospital cardiac arrest, myocardial infarction) and/or revascularizations
      (coronary artery bypass surgery or coronary angioplasty) was lower in the nurse
      intervention group (1% vs 9%; p = 0.002). We conclude that a nurse-delivered risk
      factor intervention program for patients with chest pain is feasible and more
      effective than usual care in terms of fostering lifestyle changes that may lower
      coronary risk.

PMID- 10913472
TI  - Effect of quinapril initiated during progressive remodeling in asymptomatic
      patients with healed myocardial infarction.
AB  - Approximately 20% of patients with healed myocardial infarction develop
      asymptomatic progressive left ventricular (LV) dilation and remodeling and are at
      increased risk for progression to symptomatic congestive heart failure and
      premature death. It was the goal of this study to test whether quinapril may
      interrupt this process and to analyze potential mechanisms. Of 138 patients with
      an average infarct age of 56 months, 25 had asymptomatic progressive LV dilation
      and were randomized in a prospective, double-blind study to placebo or quinapril.
      At baseline (mean +/- SEM) ejection fraction was reduced (35 +/- 3% and 39 +/-
      3%) and end-diastolic volume (gated single-photon emission computed tomography)
      increased (104 +/- 9 and 117 +/- 12 ml/m(2)) with placebo (n = 13) and quinapril
      (n = 12), respectively. Progressive dilation continued in patients taking placebo
      (6 months: 9.4 +/- 5.2 ml/m(2), 12 months 24.6 +/- 5. 4 ml/m(2); change from
      baseline: p <0.05 vs baseline; p <0.05 vs 6 months), but not with quinapril (6
      months: -0.9 +/- 4.0 ml/m(2); 12 months: 4.1 +/- 5.2 ml/m(2) [p <0.05] vs
      placebo). Wedge pressure during bicycle exercise was similar at baseline, but at
      12 months tended to be lower with quinapril (17 +/- 1 mm Hg) than with placebo
      (24 +/- 4 mm Hg, p = 0.1673). Thus, quinapril prevented further progression of
      asymptomatic LV dilation and remodeling after remote myocardial infarction,
      possibly due to attenuation of an exercise-induced increase in LV filling
      pressure.

PMID- 10913473
TI  - A prospective study of dominance and coronary heart disease in the Normative
      Aging Study.
AB  - The purpose of this study was to examine the prospective relation between
      dominance, as assessed by a Minnesota Multiphasic Personality Inventory (MMPI-2)
      derived dominance scale, and incidence of coronary heart disease (CHD),
      independent of participants' anger level. The study was performed in the VA
      Normative Aging Study, an ongoing cohort of older (mean age 61 years) men. A
      total of 1,225 men who were free of CHD in 1986 completed the MMPI-2. A factor
      analysis of selected MMPI items provided the basis for the construction of a
      dominance scale and an anger scale. During an average of 8 years of follow-up,
      158 cases of incident CHD occurred, including 29 cases of fatal CHD, 69 cases of
      nonfatal myocardial infarction (MI), and 60 cases of angina pectoris (AP).
      Compared with men reporting the lowest levels of dominance (lower tertile), the
      multivariate-adjusted relative risk among men reporting the highest levels of
      dominance (upper tertile) was 1.80 (95% confidence interval [CI] 1.21 to 3.24)
      for combined nonfatal MI and fatal CHD. Additional adjustment for anger scores
      did not significantly alter this relation. There was no significant relation
      between dominance and AP. Our data suggest that dominance is an independent risk
      factor for CHD in older men.

PMID- 10913474
TI  - In vivo demonstration of an antithrombin effect of abciximab.
AB  - Abciximab prolonged the activated clotting time (ACT) in a post hoc analysis from
      the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing
      Ischemic Complications trial and an in vitro study has suggested an antithrombin
      effect of platelet glycoprotein IIb/IIIa inhibition. The purpose of this study
      was to evaluate the in vivo effects of abciximab on ACT and thrombin generation.
      In 46 patients undergoing coronary intervention, 24 received heparin and
      abciximab (group I), whereas 22 received heparin alone (group II). All received
      the same dose (70 U/kg) of heparin. Heparin was given after a baseline ACT, and
      in group I, abciximab was administered after the 5-minute ACT. Serial ACTs were
      recorded at baseline, 5, 10, 20, and every 30 minutes thereafter and at the
      procedure's end. No intervention including balloon angioplasty was performed
      until after the 20-minute ACT. The prothrombin fragment F1.2 (Nm/L) was measured
      at baseline, 20 minutes, and at the end of the procedure. Before (baseline)
      heparin and at 5 minutes, ACTs were similar. Abciximab prolonged ACT by a mean of
      34 to 64 seconds starting with the 10-minute ACT and extending to the 50-minute
      ACT (all p <0.01 vs heparin alone). There was a progressive decrease in the F1.2
      with abciximab, and baseline minus end F1.2 was 0.12 +/- 0.02 in group I versus
      0.05 +/- 0.04 in group II, p <0.05. These data indicate a significant in vivo
      effect of abciximab plus heparin in increasing ACT and decreasing F1.2, results
      that are consistent with an effect on reducing thrombin generation.

PMID- 10913475
TI  - Comparison of baseline and low-dose dobutamine technetium-99m sestamibi
      scintigraphy with low-dose dobutamine echocardiography for predicting functional
      recovery after revascularization.
AB  - Injection of sestamibi during low-dose dobutamine (LDD) infusion might improve
      tracer ability to detect viable myocardium. This study investigated the potential
      value of LDD technetium-99m sestamibi (sestamibi) single-photon emission computed
      tomography (SPECT) in predicting functional recovery after revascularization by
      comparing its results with those of sestamibi SPECT at rest and of LDD
      echocardiography. Before revascularization, 23 patients with chronic coronary
      artery disease and regional left ventricular dysfunction underwent sestamibi
      SPECT at rest and, on a separate day, LDD echocardiography and sestamibi SPECT
      with tracer injection during LDD infusion. Echocardiography at rest was repeated
      after revascularization. Semiquantitative sestamibi uptake results (grading from
      0 = normal to 4 = absent) and wall motion (grading from 1 = normal to 4 =
      dyskinesia) were evaluated with a 16-segment model. The ventricular wall was
      divided into 3 vascular territories. At follow-up, 20 of 32 asynergic vascular
      territories showed functional recovery, whereas 12 showed no changes. For
      prediction of functional recovery, LDD SPECT achieved better accuracy than SPECT
      at rest (87% vs 65%, p <0.05); positive and negative predictive values of LDD
      SPECT were 90% and 83%, respectively, which was not significantly different from
      the related LDD echocardiographic values (84% and 69%). Thus, LDD sestamibi SPECT
      appears to be a promising method for detecting myocardial viability, which
      provides better accuracy than sestamibi SPECT at rest, and achieves predictive
      values comparable to those of LDD echocardiography.

PMID- 10913476
TI  - Echocardiographic determinants of mortality in patients >67 years of age with
      chronic heart failure.
AB  - This study sought to assess the prognostic significance of echocardiographic
      measurements of left and right ventricular dimensions and function in patients
      >67 years of age with chronic congestive heart failure (CHF). This is a
      retrospective follow-up of elderly patients who underwent an echocardiography in
      the tertiary cardiac center. A total of 185 patients (131 men) aged >/=68 years
      (mean +/- SD 75 +/- 5) with CHF were enrolled into the study. After undergoing a
      detailed echocardiographic examination, all patients were followed-up for a
      median of 20 months (interquartile range 9 to 36). During the follow-up period 54
      patients (29%) died. Left ventricular (LV) M-mode isovolumic relaxation time
      (IVRT), end-diastolic and end-systolic diameters, fractional shortening and mass,
      transmitral E:A ratio, and left atrial dimension, as well as New York Heart
      Association class and the age were found by Cox proportional-hazards univariate
      analyses to predict the outcome in these patients (all p <0.05). In multivariate
      analyses including these measurements, LV IVRT (p <0.04), age (p <0.03), and New
      York Heart Association class (p <0.001) were found to be the independent
      predictors of outcome. In the Kaplan-Meier analysis, patients with LV IVRT >30 ms
      had a better prognosis at 3 years (cumulative survival 78% [95% confidence
      interval 65% to 91%]) than those with LV IVRT </=30 ms (survival 52% [95%
      confidence interval 37% to 68%]). Measurements of LV performance, especially
      those obtained during diastole, are significantly related to prognosis in
      patients >67 years of age with CHF. LV M-mode IVRT is among the most important
      independent predictors of outcome in this population.

PMID- 10913477
TI  - Utility of cardiopulmonary exercise in the assessment of clinical determinants of
      functional capacity in hypertrophic cardiomyopathy.
AB  - The utility of metabolic gas exchange measurements in evaluating the severity and
      determinants of exercise limitation was studied during upright symptom-limited
      cardiopulmonary exercise in 135 consecutive patients with hypertrophic
      cardiomyopathy (HC) and 50 healthy age- and gender-matched volunteers. Peak
      oxygen consumption (VO(2)) was less than predicted (age, gender, and size) in 99%
      patients. Peak VO(2) was significantly associated with New York Heart Association
      functional class; however, there was considerable overlap of peak VO(2) between
      classes I and III (70 +/- 15%, 56 +/- 15%, 35 +/- 11%, respectively). Patients
      with abnormal blood pressure responses and patients with chronotropic
      incompetence during exercise had lower percent-predicted peak VO(2) than patients
      with normal blood pressure and heart rate responses during exercise (p = 0.0001
      and p <0.001, respectively). Percent-predicted peak VO(2) was similar in patients
      with and without resting left ventricular outflow obstruction. Of those patients
      with resting gradients, however, there was a strong inverse correlation between
      the magnitude of the gradient and peak VO(2) (r = 0.5; p <0.001). In conclusion,
      peak VO(2) is significantly related to New York Heart Association functional
      class in this group of patients with HC, but peak VO(2) is a superior measure of
      cardiovascular performance in individual patients. Our peak VO(2) data indicate
      that mechanical obstruction has an adverse pathophysiologic effect on functional
      capacity and provide the rationale to support treatments aimed at gradient
      reduction. Low peak VO(2) characteristics including those with normal or near
      normal left ventricular wall thickness suggests that measurement of peak VO(2)
      may aid in the differential diagnosis between HC and athlete's heart.

PMID- 10913478
TI  - Noninvasive assessment of left ventricular end-diastolic pressure by the response
      of the transmitral a-wave velocity to a standardized Valsalva maneuver.
AB  - Impaired relaxation is frequently masked by elevated filling pressures, resulting
      in a pseudonormal flow pattern (E/A >1.0). Because the E/A wave ratio increases
      as filling pressures rise, it is generally assumed that patients with an E/A
      ratio of <1.0 (impaired relaxation pattern) have relatively low filling
      pressures. Nevertheless, patients with an E/A ratio of <1.0 can have as
      profoundly elevated filling pressures as patients with a pseudonormal or
      restrictive filling pattern. Because left ventricular (LV) pressure during end
      diastole essentially determines atrial afterload, the response of the A-wave
      velocity to a reduction of atrial afterload by a standardized Valsalva maneuver
      should allow estimation of LV end-diastolic pressure (LVEDP) regardless of the
      baseline Doppler flow pattern. This was tested in 20 consecutive patients who
      were studied by pulse-wave Doppler echocardiography during cardiac
      catheterization. There was a close correlation between LVEDP and the change in A
      wave velocity during the Valsalva maneuver (r = 0.85, SEE 6.7 mm Hg) regardless
      of the baseline E/A ratio. In patients with a LVEDP of <15 mm Hg the A wave
      decreased by 21 +/- 15 cm/s. In patients with a LVEDP of >25 mm Hg the A wave
      increased by 18 +/- 13 cm/s. The change in the E/A ratio during Valsalva
      correlated fairly with LVEDP (r = -0.72, SEE 8.8 mm Hg), the baseline E/A ratio
      correlated poorly, and scatter was substantial (r = 0.46, SEE 11.2 mm Hg). Just
      as elevated filling pressures can mask impaired relaxation, the impaired
      relaxation pattern can mask the presence of elevated filling pressures. This can
      be revealed by testing the response of the A wave to the Valsalva maneuver,
      allowing estimation of LVEDP independent of the baseline E/A ratio.

PMID- 10913479
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- 10913480
TI  - Valentin Fuster, MD, PhD: a conversation with the editor. Interview by Roberts
      WC.

PMID- 10913481
TI  - Henry Arthur Solomon, MD: a conversation with the editor. Interview by Roberts
      WC.

PMID- 10913482
TI  - Relation of C-reactive protein to extent and severity of coronary narrowing in
      patients with stable angina pectoris or abnormal exercise tests.

PMID- 10913483
TI  - Late prognostic value of flow-mediated dilation in the brachial artery of
      patients with chest pain.

PMID- 10913484
TI  - Prognostic value of exercise testing in women after acute coronary syndromes (The
      Stockholm Female Coronary Risk Study).

PMID- 10913485
TI  - Patterns of aspirin use before hospitalization for acute myocardial infarction.

PMID- 10913486
TI  - Breast artery calcium on routine mammography as a potential marker for increased
      risk of cardiovascular disease.

PMID- 10913487
TI  - Direct assessment of palmar circulation before transradial coronary intervention
      by color Doppler ultrasonography.

PMID- 10913488
TI  - Comparison of effects of simvastatin versus atorvastatin on high-density
      lipoprotein cholesterol and apolipoprotein A-I levels.

PMID- 10913489
TI  - Role of atrial pressure in the success of electrical cardioversion of chronic
      atrial fibrillation.

PMID- 10913490
TI  - Diurnal variations of the ventricular pacing threshold in patients with cardiac
      pacemakers are not related to changes in autonomic tone.

PMID- 10913491
TI  - KL-6 as a potential new marker for amiodarone-induced pulmonary toxicity.

PMID- 10913492
TI  - Usefulness of suppression of ventricular arrhythmia by biventricular pacing in
      severe congestive cardiac failure.

PMID- 10913493
TI  - Reduced indexes of left atrial hypercoagulability in patients with severe mitral
      regurgitation.

PMID- 10913494
TI  - Pulsed Doppler echocardiographic assessment of the fetal PR interval.

PMID- 10913495
TI  - Clinical significance of pulmonary arteriovenous malformations after staging
      bidirectional cavopulmonary anastomosis.

PMID- 10913496
TI  - Behavior of C-reactive protein levels in medically treated aortic dissection and
      intramural hematoma.

PMID- 10913497
TI  - Left atrial kinetic energy in AL amyloidosis: can it detect early dysfunction?

PMID- 10913498
TI  - Increased thrombus formation relates to ambient blood glucose and leukocyte count
      in diabetes mellitus type 2.

PMID- 10913500
TI  - Aorto-left ventricular tunnel: transcatheter closure using an amplatzer duct
      occluder device.

PMID- 10913499
TI  - Aggressive Lipid-Lowering Initiation Abates New Cardiac Events (ALLIANCE)
      rationale and design of atorvastatin versus usual care in hypercholesterolemic
      patients with coronary artery disease.

PMID- 10913501
TI  - Appropriate treatment of aortic intramural hematoma.

PMID- 10913502
TI  - Lithium increases N-acetyl-aspartate in the human brain: in vivo evidence in
      support of bcl-2's neurotrophic effects?
AB  - BACKGROUND: Recent preclinical studies have shown that lithium (Li) robustly
      increases the levels of the major neuroprotective protein, bcl-2, in rat brain
      and in cells of human neuronal origin. These effects are accompanied by striking
      neuroprotective effects in vitro and in the rodent central nervous system in
      vivo. We have undertaken the present study to determine if lithium exerts
      neurotrophic/ neuroprotective effects in the human brain in vivo. METHODS: Using
      quantitative proton magnetic resonance spectroscopy, N-acetyl-aspartate (NAA)
      levels (a putative marker of neuronal viability and function) were investigated
      longitudinally in 21 adult subjects (12 medication-free bipolar affective
      disorder patients and 9 healthy volunteers). Regional brain NAA levels were
      measured at baseline and following 4 weeks of lithium (administered in a blinded
      manner). RESULTS: A significant increase in total brain NAA concentration was
      documented (p < .0217). NAA concentration increased in all brain regions
      investigated, including the frontal, temporal, parietal, and occipital lobes.
      CONCLUSIONS: This study demonstrates for the first time that Li administration at
      therapeutic doses increases brain NAA concentration. These findings provide
      intriguing indirect support for the contention that chronic lithium increases
      neuronal viability/function in the human brain, and suggests that some of Li's
      long-term beneficial effects may be mediated by neurotrophic/neuroprotective
      events.

PMID- 10913504
TI  - Attention-deficit disorder and conduct disorder in girls: evidence for a familial
      subtype.
AB  - BACKGROUND: The frequent comorbidity between attention-deficit/hyperactivity
      disorder (ADHD) and conduct disorder (CD) raises the possibility that ADHD+CD is
      a distinct and separate condition. METHODS: We tested hypotheses about patterns
      of familial association between ADHD, CD, oppositional defiant disorder (ODD) and
      adult antisocial personality disorder (ASPD). Using family study methodology in a
      sample of girls, we found 11 children with diagnoses of ADHD+ CD, 39 with
      ADHD+ODD, and 90 with ADHD only. These were compared with 122 non-ADHD, non-CD
      control probands. Familial risk analysis was utilized. RESULTS: Relatives of each
      ADHD proband subgroup were at significantly greater risk for ADHD, and the
      relatives of ADHD-only subjects were at a greater risk of ODD than relatives of
      control subjects. Also, rates of CD were elevated among relatives of ADHD+CD
      probands only, and the coaggregation of ADHD and the antisocial disorders could
      not be accounted for by marriages between ADHD and antisocial spouses. Both ADHD
      and antisocial disorders occurred in the same relatives more often than expected
      by chance. CONCLUSIONS: These findings suggest that ADHD with and without
      antisocial disorders may be etiologically distinct disorders and provide evidence
      for the nosologic validity of ICD-10 hyperkinetic conduct disorder.

PMID- 10913503
TI  - Attention-deficit/hyperactivity disorder in adults: an overview.
AB  - To assess the validity of adult attention-deficit/hyperactivity disorder (ADHD),
      we reviewed clinical, family, psychopharmacologic, neurobiological, and outcome
      studies. We found multiple reports describing adults with clinical features
      highly reminiscent of the childhood ADHD. These adults, who are impulsive,
      inattentive, and restless, have the clinical "look and feel" of ADHD children. As
      with their childhood counterparts, many adults with ADHD suffer from antisocial,
      depressive, and anxiety disorders. They also show clinically significant
      impairments--histories of school failure, occupational problems, and traffic
      accidents. Studies of biological features show correspondences between child and
      adult cases of ADHD. Both show familial aggregation and a characteristic profile
      of neuropsychologic deficits; an emerging neuroimaging literature suggests that
      abnormalities in the same brain regions underlie both the child and adult forms
      of the disorder. Although these converging lines of evidence support the validity
      of ADHD in adults, follow-up studies of ADHD children have yielded ambiguous
      results. This ambiguity is in part due to differences in how researchers define
      the persistence of ADHD, a problem that suggests future research focus on how
      best to diagnose ADHD in adulthood.

PMID- 10913505
TI  - Differential limbic--cortical correlates of sadness and anxiety in healthy
      subjects: implications for affective disorders.
AB  - BACKGROUND: Affective disorders are associated with comorbidity of depression and
      anxiety symptoms. Positron emission tomography resting-state studies in affective
      disorders have generally failed to isolate specific symptom effects. Emotion
      provocation studies in healthy volunteers have produced variable results, due to
      differences in experimental paradigm and instructions. METHODS: To better
      delineate the neural correlates of sad mood and anxiety, this study used
      autobiographical memory scripts in eight healthy women to generate sadness,
      anxiety, or a neutral relaxed state in a within-subject design. RESULTS: Sadness
      and anxiety, when contrasted to a neutral emotional state, engaged a set of
      distinct paralimbic-cortical regions, with a limited number of common effects.
      Sadness was accompanied by specific activations of the subgenual cingulate area
      (BA) 25 and dorsal insula, specific deactivation of the right prefrontal cortex
      BA 9, and more prominent deactivation of the posterior parietal cortex BAs 40/7.
      Anxiety was associated with specific activations of the ventral insula, the
      orbitofrontal and anterior temporal cortices, specific deactivation of
      parahippocampal gyri, and more prominent deactivation of the inferior temporal
      cortex BAs 20/37. CONCLUSIONS: These findings are interpreted within a model in
      which sadness and anxiety are represented by segregated corticolimbic pathways,
      where a major role is played by selective dorsal cortical deactivations during
      sadness, and ventral cortical deactivations in anxiety.

PMID- 10913506
TI  - Activation of anterior paralimbic structures during guilt-related script-driven
      imagery.
AB  - BACKGROUND: Several recent neuroimaging studies have examined the neuroanatomical
      correlates of normal emotional states, such as happiness, sadness, fear, anger,
      anxiety, and disgust; however, no previous study has examined the emotional state
      of guilt. METHODS: In the current study, we used positron emission tomography and
      the script-driven imagery paradigm to study regional cerebral blood flow (rCBF)
      during the transient emotional experience of guilt in eight healthy male
      participants. In the Guilt condition, participants recalled and imagined
      participating in a personal event involving the most guilt they had ever
      experienced. In the Neutral condition, participants recalled and imagined
      participating in an emotionally neutral personal event. RESULTS: In the Guilt
      versus Neutral comparison, rCBF increases occurred in anterior paralimbic regions
      of the brain: bilateral anterior temporal poles, anterior cingulate gyrus, and
      left anterior insular cortex/inferior frontal gyrus. CONCLUSIONS: These results,
      along with those of previous studies, are consistent with the notion that
      anterior paralimbic regions of the brain mediate negative emotional states in
      healthy individuals.

PMID- 10913507
TI  - A pilot study of amygdala volumes in pediatric generalized anxiety disorder.
AB  - BACKGROUND: The neurodevelopment of childhood anxiety disorders is not well
      understood. Basic research has implicated the amygdala and circuits related to
      these nuclei as being central to several aspects of fear and fear-related
      behaviors in animals. METHODS: Magnetic resonance imaging was used to measure
      amygdala volumes and comparison brain regions in 12 child and adolescent subjects
      with generalized anxiety disorder and 24 comparison subjects. Groups were matched
      on age, sex, height, and handedness and were also similar on measures of weight,
      socioeconomic status, and full scale IQ. RESULTS: Right and total amygdala
      volumes were significantly larger in generalized anxiety disorder subjects.
      Intracranial, cerebral, cerebral gray and white matter, temporal lobe,
      hippocampal, and basal ganglia volumes and measures of the midsagittal area of
      the corpus callosum did not differ between groups. CONCLUSIONS: Although these
      data are preliminary and from a small sample, the results are consistent with a
      line of thinking that alterations in the structure and function of the amygdala
      may be associated with pediatric generalized anxiety disorder.

PMID- 10913508
TI  - Lithium regulation of aldolase A expression in the rat frontal cortex:
      identification by differential display.
AB  - BACKGROUND: Substantial evidence indicates that lithium may exert its therapeutic
      effects through progressive adaptive changes at the level of gene expression;
      however, the study of lithium-regulated genes has been primarily undertaken with
      the "candidate gene" approach based on a specific testable hypothesis. The aim of
      our study was to identify lithium-regulated genes that would not be predicted a
      priori by the candidate gene approach. METHODS: Differential display polymerase
      chain reaction was used to isolate and identify messenger RNAs (mRNAs) that are
      differentially expressed in the frontal cortex of rats given lithium for 5 weeks
      to achieve plasma lithium concentrations of 0.6 to 0.9 mmol/L. RESULTS: A
      putative lithium-regulated complementary DNA fragment (LRG1) was identified.
      Northern blot analysis revealed that 5 weeks of lithium treatment, but not 1
      week, significantly reduced LRG1 mRNA levels. LRG1 mRNA levels were similarly
      reduced by 5 weeks of carbamazepine, but not valproate administration. Sequence
      analysis and search of the GenBank database revealed that LRG1 is analogous to
      the sequence of the gene for rat aldolase A. CONCLUSIONS: These results
      demonstrate that chronic administration of lithium, but not short-term
      administration, down regulates the levels of aldolase A mRNA, suggesting this
      effect may play a role in mediating the therapeutic action of this agent.

PMID- 10913509
TI  - Elevated plasma thymopoietin associated with therapeutic nonresponsiveness in
      major depression.
AB  - BACKGROUND: Stress predisposes to major depression, and hyperactivity of the
      stress-activated hypothalamic-pituitary-adrenal (HPA) axis occurs in this
      disease. Thymopentin, an active fragment of thymopoietin (TP), reduces endocrine
      and behavioral responses to experimental stress, possibly by lowering plasma TP
      (pTP) levels. METHODS: Plasma TP and the HPA hormones arginine vasopressin
      (pAVP), adrenocorticotropic hormone (pACTH), and plasma cortisol (pCORT) were
      measured in 21 untreated depressed patients and 21 matched control subjects.
      Clinical responses to antidepressants were evaluated in 17 depressed patients.
      RESULTS: Plasma TP was elevated in depression (p < .002), with in 8 out of 21
      (38%) depressed patients having significant elevations (p < .03). For 17 patients
      whose antidepressant responses were evaluated, nonresponsiveness occurred in 6
      out of 7 (86%) with elevated pTP (>7.5 pg/mL) versus 3 out of 10 (30%) with
      normal pTP (p < .05). CONCLUSIONS: The significant association of elevated pTP
      with nonresponsiveness to antidepressant drugs may signify a distinct
      pathogenesis for the depression of patients with elevated pTP.

PMID- 10913510
TI  - Similarity in saliva cortisol measures in monozygotic twins and the influence of
      past major depression.
AB  - BACKGROUND: Some studies suggest that cortisol may be under genetic control. The
      aims of our study were to investigate the familial resemblance in morning and
      evening cortisol secretion as assessed by saliva cortisol and to assess the
      influence of history of major depression. METHODS: Women for this investigation
      were selected from an ongoing study in female-female twin pairs ascertained from
      the Virginia Twin Registry. Telephone screening assured that current
      inclusion/exclusion criteria were met. Subjects were asked to collect AM samples
      within 45 min after awakening, and evening samples immediately before bedtime for
      14 days. RESULTS: There was a high degree of correlation across weeks in both the
      AM and PM cortisol values, indicating significant stability across individuals.
      There was significant correlation between AM and PM cortisol in monozygotic
      twins. In twins with a history of major depression (n = 30), compared with the
      twins without past major depression (n = 28), there was a trend towards higher
      cortisol (p = .056). CONCLUSIONS: These results suggest that around 40-45% of the
      total variance in salivary cortisol is shared by monozygotic twins. Although the
      increase in baseline cortisol in twins with a history of major depression is only
      significant at the trend level, the effect size is comparable to an "in episode"
      depressed population.

PMID- 10913512
TI  - Present issues in the determination of troponins and other markers of cardiac
      damage.
AB  - OBJECTIVE: To review some of the recently proposed improvements and the
      corresponding apparent issues in the field of biochemical markers of cardiac
      damage. CONCLUSIONS: The continuous development of new analytical tools for the
      biochemical evaluation of patients with suspected myocardial injury brings
      without doubt new challenges of careful technological evaluation, implementation,
      and standardization but it may also provide a unique opportunity to markedly
      enhance our diagnostic performance in the clinical setting of acute coronary
      syndrome.

PMID- 10913511
TI  - Acute effects of mirtazapine on sleep continuity and sleep architecture in
      depressed patients: a pilot study.
AB  - BACKGROUND: Mirtazapine, a clinically effective antidepressant, acts by
      antagonizing central alpha2-adrenergic and 5-HT2/5-HT3 receptors. No data are
      available regarding mirtazapine's effects on sleep architecture in patients with
      major depressive disorder. METHODS: Six patients meeting criteria for major
      depressive disorder and scoring > or =4 on the three Hamilton Depression Rating
      Scale sleep items were studied. Polysomnographic evaluations were performed at
      baseline and after 1 (15 mg at bedtime) and 2 weeks (30 mg at bedtime) of open
      label mirtazapine treatment. RESULTS: Mirtazapine significantly decreased sleep
      latency and significantly increased total sleep time and sleep efficiency from
      baseline levels during week 1, with similar results observed after week 2.
      Mirtazapine did not significantly alter rapid eye movement sleep parameters.
      Clinically, Hamilton Depression Rating Scale and sleep disturbance ratings
      improved after treatment. CONCLUSIONS: Mirtazapine significantly improves sleep
      continuity in major depressive disorder patients with poor sleep quality at weeks
      1 and 2 of treatment, while preserving sleep architecture.

PMID- 10913513
TI  - Preliminary study pointing out a significant alteration in the biochemical
      composition of MUC2 in colorectal mucinous carcinoma.
AB  - OBJECTIVES: In this study, we characterized colonic MUC2 mucin from a mucinous
      carcinoma cell line and tried to find out carcinoma-associated alterations by
      comparing the results with those obtained from its benign phenotype previously.
      DESIGN AND METHODS: The molecular size distribution of the extracted molecules
      and their reactivity with two different MUC2 polypeptide antibodies indicated the
      presence of precursor and mature forms of the mucin in both cell lines. Isopycnic
      density gradient centrifugation gave good resolution of mature and precursor
      forms of MUC2 as assessed by agarose gel electrophoresis. Using this approach, we
      compared the different forms of MUC2 between benign and malign colonic cells.
      RESULTS: In the comparison, we detected some aberrant glycosylated MUC2 molecules
      in mucinous carcinoma cell line. Agarose gel electrophoretic analysis of the low
      density fractions indicated that these molecules are more charged than
      precursors, however, they are smaller and/or less glycosylated than mature MUC2
      molecules. CONCLUSION: The identification of unusual partially glycosylated forms
      of the major colonic mucin MUC2 is novel and unexpected. Implication of defective
      processes in the post translational modification/ processing of MUC2 opens a new
      field in the cancer mucin biology.

PMID- 10913514
TI  - Reference values and methods comparison of a new testosterone assay on the AxSYM
      system.
AB  - OBJECTIVES: We have contributed to the Design Validation Protocol of the new
      Abbott AxSYM Testosterone assay with a study on reference values and methods
      comparison. DESIGN AND METHODS: For reference values a population of 45 women and
      30 men was tested. In methods comparison, 132 samples for the AxSYM vs. ACS-180,
      and 30 for the AxSYM vs. Elecsys were used. Pearson and intraclass concordance
      coefficients and Passing-Bablock test were performed for overall group, men and
      women. RESULTS: Reference values were 0.9-3.1 (females) and 1.0-30.2 nmol/L
      (males). Globally, a good agreement between methods in both the AxSYM vs. ACS-180
      (slope: 0.88, y-intercept: 0.67, r = 0.961) and the AxSYM vs. Elecsys (slope:
      1.08, y-intercept: 0.31, r = 0.935) studies was found. Slightly worse results
      were observed for women. CONCLUSIONS: The reference range of testosterone by the
      AxSYM system matches with those published for other methods. An acceptable
      agreement between the AxSYM Testosterone assay and both a classical (ACS-180) and
      a more recent (Elecsys) methodology was observed.

PMID- 10913515
TI  - Measurement of nine human milk proteins by nephelometric immunoassays:
      application to the determination of mature milk protein profile.
AB  - OBJECTIVES: Microparticle-enhanced nephelometric immunoassays for six human milk
      proteins (beta-casein, kappa-casein, alpha-lactalbumin, serum albumin,
      lactoferrin, and lysozyme) and conventional immunonephelometry assays for
      immunoglobulin A, C3, and C4 complement proteins were developed and
      characterized. DESIGN AND METHODS: Microparticle-enhanced nephelometric
      immunoassays are competitive assays based on the nephelometric quantification of
      the inhibition of microparticle-protein conjugates immunoagglutination by the
      proteins to be assayed. RESULTS: High precision (CVs ranged from 1% to 14% in
      within- and between-assays) and recovery (linear recovery in dilution-overloading
      assay) ensure a reliable determination of the main human milk proteins by single
      step homogeneous nephelometric immunoassays, accurate over wide ranges of
      concentration. These immunoassays were easily applied to a large number of mature
      human milk samples (between 373 and 503 according to the proteins tested).
      CONCLUSIONS: The immunoassays developed could be applied to the fast
      determination of human milk protein profile usable for nursery milk bank and
      fortification.

PMID- 10913516
TI  - Chemical precipitation of apolipoprotein B-containing lipoproteins facilitates
      determination of LDL particle size.
AB  - OBJECTIVES: To simplify the determination of low-density lipoprotein (LDL)
      particle size by eliminating the need for ultracentrifugation. DESIGN AND
      METHODS: We compared LDL particle size determination by gradient gel
      electrophoresis using two different methods for separation of LDL: (a) by
      ultracentrifugation with a density between 1.019 and 1.063 g/mL, and (b) by
      precipitation of the apolipoprotein B-containing lipoproteins from plasma. LDL
      particle size was determined for 41 individuals using both methods. RESULTS: The
      correlation between these two methods was r = 0.98; peak particle diameter (nm)
      was reproducible with a coefficient of variation of 1. 3% for LDL separated by
      ultracentrifugation and 1.4% for LDL prepared by precipitation. The intra-assay
      variation within a single gel was 0.2%. CONCLUSION: Elimination of the need for
      ultracentrifugation or lipid staining significantly reduces the cost and
      simplifies the procedure of LDL particle sizing. As a result, larger patient
      populations can be more readily screened for the determination of LDL particle
      size.

PMID- 10913517
TI  - Evaluation of a particle-enhanced turbidimetric immunoassay for the measurement
      of ferritin: application to patients participating in an autologous blood
      transfusion program.
AB  - OBJECTIVES: To evaluate a turbidimetric immunoassay for the measurement of
      ferritin, and to assay this method in a group of patients undergoing an
      autologous blood transfusion program. DESIGN AND METHODS: We used an ILab 900
      analyzer. This instrument automates a particle-enhanced immunoturbidimetric assay
      with an analysis time of 9 min. This technique was compared with a microparticle
      immunoassay. The turbidimetric assay was used to measure ferritin in a group of
      30 patients undergoing an autologous blood transfusion program. RESULTS: The
      assay was linear in the range 3-1400 microg/L (r = 0.9999). The intra- and inter
      assay imprecision (CV) at 20, 97 and 469 microg/L were <3.0 and <5.0%,
      respectively. Recovery was 88. 7 to 97.4%. The detection limit was 3 microg/L.
      Hemoglobin (</=4 g/L), mild hyperbilirubilinemia (bilirubin </=50 micromol/L),
      triglycerides (</=10 mmol/L) and myeloma paraproteins did not interfere with the
      assay. The assay showed good correlation with a microparticle enzymoimmunoassay
      (r = 0.994) with a mean difference between methods of -6 +/- 16 microg/L. This
      method was sensitive, accurate, and fast enough for an efficient follow-up of
      autologous blood transfusion patients. CONCLUSIONS: The new automated serum assay
      for ferritin is an attractive alternative that avoids the need for dedicated
      instrumentation.

PMID- 10913519
TI  - Mycophenolate mofetil in stem cell transplant patients in relation to plasma
      level of active metabolite.
AB  - OBJECTIVES: To investigate mycophenolate mofetil (MMF) plasma levels and impact
      on acute graft versus host disease (aGvHD) after stem cell transplantation (SCT).
      METHODS: SCT patients (n = 14) with aGvHD (>/= II) receiving MMF (1-3 g/d) in
      addition to cyclosporine, prednisolone, and methotrexate for aGvHD prophylaxis
      were investigated. Plasma levels of mycophenolic acid (MPA) and its glucuronide
      metabolite (MPAG) were determined by high-performance liquid chromatography.
      RESULTS: Overall median steady state pre-dose plasma MPA concentration was 0.47
      mg/L and increased within 75 min after administration to 1.64 mg/L. In comparison
      to patients with skin aGvHD, patients with gut aGvHD had lower MPA
      concentrations, both pre-dose (p = 0.16) and after 75 min, (p = 0.02). All 7
      patients with skin aGvHD but only 2 patients with gut aGvHD responded to MMF.
      Overall, the pre-dose plasma MPA concentration was significantly (p = 0.007)
      greater in responders (n = 9) than in non-responders (n = 5). CONCLUSION: MMF
      seems to be an effective treatment for aGvHD in SCT patients particular in those
      patients without gut involvement.

PMID- 10913518
TI  - Expression of the genetic variants of human alpha-1-acid glycoprotein in cancer.
AB  - OBJECTIVES: We have investigated the AAG and its genetic variants concentrations
      in plasma samples of 61 patients suffering from different types of cancers.
      DESIGN AND METHODS: The patients were shared out in three groups, breast, lung,
      and ovary cancers groups. AAG concentration was measured by an
      immunonephelometric method and the phenotype was determined, after desialylation
      of plasma by analytical isoelectric focusing. Detection of AAG variants was made
      by immunoblotting and their proportions were determined by laser densitometry
      analysis. A population of 74 healthy individuals served as controls. RESULTS: The
      plasma concentrations of AAG in the breast and lung cancer groups were 2.5 times
      increased, while in the ovary cancer group, the concentrations were 1.6 times
      increased. AAG concentrations in the cancer population ranged between 0.45 and
      2.85 g/L (mean value 1.12 +/- 0.51 g/L). The proportions of the ORM1 and ORM2
      variants were similar to those in the healthy population. In breast and lung
      cancer groups, the relative concentrations of genetic variants were increased
      more than 2.5 fold, whereas a 1. 6-fold increase was observed in the ovary cancer
      group. CONCLUSIONS: These results show that AAG plasma concentrations are
      increased in these types of cancers and that changes in the expression of the
      genetic variants of AAG could also occur according to the type of cancer.

PMID- 10913520
TI  - Lipid peroxidation and antioxidant system in the blood of patients with Hodgkin's
      disease.
AB  - OBJECTIVES: The purpose of this study was to measure the extent of lipid
      peroxidation and the status of antioxidants in patients with Hodgkin's disease.
      DESIGN AND METHODS: Glutathione peroxidase (GPX) and superoxide dismutase (SOD)
      activities, and malondialdehyde (MDA), selenium, zinc and copper content have
      been measured in 20 patients with Hodgkin's disease and 30 age-matched controls.
      RESULTS: Significantly higher concentrations of MDA in plasma as well as in
      erythrocytes were found compared to the control group. In both plasma and
      erythrocytes, GPX activity, selenium and zinc levels were significantly lower in
      patients than in controls. However, SOD activity in erythrocytes and copper
      levels in both plasma and erythrocytes were significantly higher in patients.
      CONCLUSION: We conclude that the antioxidant system is impaired in Hodgkin's
      disease due to the abnormal metabolism of trace elements and antioxidant enzymes.

PMID- 10913521
TI  - Evaluation of the Roche diagnostics LightCycler-Factor V Leiden Mutation
      Detection Kit and the LightCycler-Prothrombin Mutation Detection Kit.

PMID- 10913522
TI  - Evaluation of the accuracy of enzymatically determined carrier status for Krabbe
      disease by DNA-based testing.

PMID- 10913523
TI  - Identification of exon 1 of prostase/KLK-L1 gene.

PMID- 10913575
TI  - Gigerenzer's normative critique of Kahneman and Tversky.
AB  - Gigerenzer has argued that it may be inappropriate to characterize some of the
      biases identified by Kahneman and Tversky as "errors" or "fallacies," for three
      reasons: (a) according to frequentists, no norms are appropriate for single-case
      judgments because single-case probabilities are meaningless; (b) even if single
      case probabilities make sense, they need not be governed by statistical norms
      because such norms are "content-blind" and can conflict with conversational
      norms; (c) conflicting statistical norms exist. I try to clear up certain
      misunderstandings that may have hindered progress in this debate. Gigerenzer's
      main point turns out to be far less extreme than the position of "normative
      agnosticism" attributed to him by Kahneman and Tversky: Gigerenzer is not denying
      that norms appropriate for single-case judgments exist, but is rather complaining
      that the existence and the nature of such norms have been dogmatically assumed by
      the heuristics and biases literature. In response to this complaint I argue that
      single-case probabilities (a) make sense and (b) are governed by probabilistic
      norms, and that (c) the existence of conflicting statistical norms may be less
      widespread and less damaging than Gigerenzer thinks.

PMID- 10913576
TI  - Causal cognition in a non-human primate: field playback experiments with Diana
      monkeys.
AB  - Crested guinea fowls (Guttera pucherani) living in West African rainforests give
      alarm calls to leopards (Panthera pardus) and sometimes humans (Homo sapiens),
      two main predators of sympatric Diana monkeys (Cercopithecus diana). When hearing
      these guinea fowl alarm calls, Diana monkeys respond as if a leopard were
      present, suggesting that by default the monkeys associate guinea fowl alarm calls
      with the presence of a leopard. To assess the monkeys' level of causal
      understanding, I primed monkeys to the presence of either a leopard or a human,
      before exposing them to playbacks of guinea fowl alarm calls. There were
      significant differences in the way leopard-primed groups and human-primed groups
      responded to guinea fowl alarm calls, suggesting that the monkeys' response was
      not directly driven by the alarm calls themselves but by the calls' underlying
      cause, i.e. the predator most likely to have caused the calls. Results are
      discussed with respect to three possible cognitive mechanisms - associative
      learning, specialized learning programs, and causal reasoning - that could have
      led to causal knowledge in Diana monkeys.

PMID- 10913577
TI  - The task-specific nature of domain-general reasoning.
AB  - This paper develops a theory of how interpretative processes constrain
      inferential performance on conditional reasoning tasks. Experiment 1 investigated
      the hypothesis that performance on common reasoning tasks is mediated by
      different interpretive variables. Necessity and sufficiency relations predicted
      performance on the conditional arguments task, whereas on the Wason task,
      performance was predicted by whether the conditional statement instantiated a
      deontic or a factual relation. Performance on the truth-table task was predicted
      by both sets of variables. Experiment 2 explored the mapping relation between
      interpretation, representation, and inference. It was observed that conditional
      responses to the Wason and arguments tasks were based on different
      representations of the conditional relationship. These data rule out a simple
      model of the interplay between interpretation and reasoning in which the
      interpretation of a statement is driven solely by its content, and instead,
      indicate that the interpretation of conditional relations is task-specific.

PMID- 10913578
TI  - Representation, space and Hollywood Squares: looking at things that aren't there
      anymore.
AB  - It has been argued that the human cognitive system is capable of using spatial
      indexes or oculomotor coordinates to relieve working memory load (Ballard, D. H.,
      Hayhoe, M. M., Pook, P. K., & Rao, R. P. N. (1997). Behavioral and Brain
      Sciences, 20(4), 723), track multiple moving items through occlusion (Scholl, D.
      J., & Pylyshyn, Z. W. (1999). Cognitive Psychology, 38, 259) or link incompatible
      cognitive and sensorimotor codes (Bridgeman, B., & Huemer, V. (1998).
      Consciousness and Cognition, 7, 454). Here we examine the use of such spatial
      information in memory for semantic information. Previous research has often
      focused on the role of task demands and the level of automaticity in the encoding
      of spatial location in memory tasks. We present five experiments where location
      is irrelevant to the task, and participants' encoding of spatial information is
      measured implicitly by their looking behavior during recall. In a paradigm
      developed from Spivey and Geng (Spivey, M. J., & Geng, J. (2000). submitted for
      publication), participants were presented with pieces of auditory, semantic
      information as part of an event occurring in one of four regions of a computer
      screen. In front of a blank grid, they were asked a question relating to one of
      those facts. Under certain conditions it was found that during the question
      period participants made significantly more saccades to the empty region of space
      where the semantic information had been previously presented. Our findings are
      discussed in relation to previous research on memory and spatial location, the
      dorsal and ventral streams of the visual system, and the notion of a cognitive
      perceptual system using spatial indexes to exploit the stability of the external
      world.

PMID- 10913579
TI  - alpha-fluoromethylhistidine depletes histamine from secreting but not from non
      secreting rat stomach ECL cells.
AB  - Histamine in the oxyntic mucosa of the rat stomach occurs in mast cells (10%) and
      ECL cells (90%). Unlike the mast cells, the ECL cells operate under the control
      of gastrin. alpha-Fluoromethylhistidine, an irreversible inhibitor of the
      histamine-forming enzyme, histidine decarboxylase depletes ECL-cell but not mast
      cell histamine. This report shows that the effectiveness by which histidine
      decarboxylase inhibition depletes ECL-cell histamine depends on the rate of
      histamine secretion. Rats received alpha-fluoromethylhistidine by continuous
      subcutaneous infusion for 24 h. Maximally effective doses (>/=3 mg/kg/h)
      inhibited histidine decarboxylase and reduced oxyntic mucosal histamine in fed
      rats by 80-90%. In fasted rats, the reduction was 50%. alpha
      Fluoromethylhistidine greatly reduced the number of histamine-immunoreactive ECL
      cells (immunocytochemistry) and of secretory vesicles in the ECL cells (electron
      microscopy) in fed but not in fasted rats. The half-life of oxyntic mucosal
      histamine (determined upon histidine decarboxylase inhibition) was 2.6 h in fed
      rats and 19.4 h in fasted rats. The amount of histamine secreted in response to
      gastrin (monitored by gastric submucosal microdialysis) was greatly reduced by
      alpha-fluoromethylhistidine in fed rats but not in fasted rats. ECL cells were
      isolated from rat stomach by elutriation (80% purity). Their histamine content
      was determined after culture, with or without alpha-fluoromethylhistidine, in the
      presence of varying concentrations of gastrin. In a medium containing 10 nM
      gastrin, ECL cells responded to a maximally effective concentration of alpha
      fluoromethylhistidine (0.1 nM) with 80% reduction in histamine content. In the
      absence of gastrin, ECL cells responded to alpha-fluoromethylhistidine with 45%
      reduction of histamine; the releasable histamine pool was unaffected. In
      conclusion, the combination of histidine decarboxylase inhibition and a high rate
      of histamine secretion will promptly exhaust the ECL-cell histamine pool, while
      histidine decarboxylase inhibition and a low secretion rate will affect the
      histamine pool much less.

PMID- 10913580
TI  - Stereospecific modulation of GABA(A) receptor function by urocanic acid isomers.
AB  - A deamination product of histidine, urocanic acid, accumulates in the skin of
      mammals as trans-urocanic acid. Ultraviolet (UV) irradition converts it to the
      cis-isomer that is an important mediator in UV-induced immunosuppression. We have
      recently shown that urocanic acid interferes with the agonist binding to GABA(A)
      receptors. We now report that the effects of urocanic acid on binding of a
      convulsant ligand (t-butylbicyclo[35S]phosphorothionate) to GABA(A) receptors in
      brain membrane homogenates are dependent on pH of the incubation medium, the
      agonistic actions being enhanced at the normal pH of the skin (5.5). Using
      Xenopus laevis oocytes expressing recombinant rat alpha1beta1gamma2S GABA(A)
      receptors, the low pH potentiated the direct agonistic action of trans-urocanic
      acid under two-electrode voltage-clamp, whereas cis-urocanic acid retained its
      low efficacy both at pH 5.5 and 7.4. The results thus indicate clear differences
      between urocanic acid isomers in functional activity at one putative receptor
      site of immunosuppression, the GABA(A) receptor, the presence of which in the
      skin remains to be demonstrated.

PMID- 10913581
TI  - S-nitroso-N-acetylpenicillamine and nitroprusside induce apoptosis in a neuronal
      cell line by the production of different reactive molecules.
AB  - CHP212 neuroblastoma cells were exposed to two different nitric oxide (NO)
      donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside. Apoptosis and
      necrosis were determined with flow cytometric analysis of annexin V binding and
      propodium iodide uptake. Both S-nitroso-N-acetylpenicillamine and sodium
      nitroprusside induced apoptosis, but with a different time dependency.
      Oxyhemoglobin (NO scavenger) attenuated the toxicity of S-nitroso-N
      acetylpenicillamine, but had no effect on the toxicity of sodium nitroprusside.
      By contrast, deferoxamine (iron chelator) attenuated the toxicity of sodium
      nitroprusside, but had no effect on the toxicity of S-nitroso-N
      acetylpenicillamine. Urate (ONOO(-) scavenger) did not influence the toxicity of
      either S-nitroso-N-acetylpenicillamine or sodium nitroprusside, but protected
      from SIN-1 (3-morpholinosydnonimine, ONOO(-) donor). It was shown that both
      dithiothreitol and ascorbic acid affected the toxicity of S-nitroso-N
      acetylpenicillamine and sodium nitroprusside in opposite ways. In the presence of
      dithiothreitol, superoxide dismutase and catalase decreased the toxicity of
      sodium nitroprusside. In the presence of cells, but not in their absence, S
      nitroso-N-acetylpenicillamine decomposed with a half-life of about 4 h as
      assessed by the production of nitrite and absorbance reduction at 335 nm. Sodium
      nitroprusside decomposed very slowly in the presence of cells as assessed by the
      production of ferrocyanide. It can be concluded that (1) slow and sustained
      release of NO from S-nitroso-N-acetylpenicillamine at the cell surface causes
      apoptosis in CHP212 cells, probably without the involvement of ONOO(-), (2)
      sodium nitroprusside causes apoptosis by the production of H(2)O(2) and/or iron,
      rather than NO, and probably has to be taken up by the cell for decomposition.

PMID- 10913582
TI  - Effects of trazodone on neurotransmitter release from rat mossy fibre cerebellar
      synaptosomes.
AB  - The effects of trazodone and putative sigma (sigma) receptor ligands were
      investigated on KCl-stimulated release of glutamate (Glu) and gamma-aminobutyric
      acid (GABA) from cerebellar mossy fibre synaptosomes. Both trazodone and
      serotonin (5-HT) inhibited the increase of Glu and GABA release evoked by 15 mM
      KCl. Trazodone increased the inhibition of Glu release caused by 0.01 microM 5
      HT, while it antagonized the inhibition induced by higher 5-HT concentrations.
      Despite the low affinity of trazodone for both sigma(1) and sigma(2) binding
      sites, with a pK(i) of 5.9 and 6.0 respectively, two sigma receptor ligands, (+)
      3-[3-hydroxypheny]-N-(1-propyl)piperidine ((+)-3-PPP) and N-[2-(3,4
      dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047) antagonized
      the effects of trazodone. The putative sigma receptor ligand N-allylnormetazocine
      ((+)-SKF 10,047) mimicked the inhibitory effect of trazodone. As with trazodone,
      (+)-3-PPP and BD 1047 antagonized the activity of (+)-SKF 10,047 but not that of
      5-HT. On the whole, these results suggest that trazodone shares a common
      molecular target with sigma compounds distinct from that of 5-HT and is involved
      in K(+)-stimulated Glu and GABA release from mossy fibre cerebellar synaptosomes.

PMID- 10913583
TI  - Positive effect of bumetanide on contractile activity of ventricular
      cardiomyocytes.
AB  - Although the beneficial effects of loop-diuretics in relieving congestive heart
      failure and essential hypertension are well established, there has been limited
      investigation into the direct cardiac effect of these drugs. The aim of the
      present study was to investigate mechanical and electrophysiological effects of
      three loop-diuretics, namely, frusemide, bumetanide and torasemide, in
      ventricular cardiomyocytes isolated from rabbit myocardium. Contractile
      performance was assessed using a video edge detection method and effects on L
      type Ca(2+) currents were determined using a 'perforated' patch-clamp technique.
      Unlike frusemide and torasemide, bumetanide produced concentration-dependent
      (3x10(-8) to 10(-5) M) increases in cell shortening and velocity of cell
      shortening. Neither frusemide, bumetanide nor torasemide exerted any action on
      peak Ca(2+) current amplitudes. In summary, the present investigation provides
      evidence for a direct contractile effect of the loop diuretic, bumetanide, in
      contrast to absence of effects by frusemide and torasemide, in ventricular
      cardiomyocytes isolated from rabbit myocardium.

PMID- 10913584
TI  - Binding properties of [3H]MS-377, a novel sigma receptor ligand, to rat brain
      membranes.
AB  - MS-377 ((R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]++ +methy
      l-2-pyrrolidinone L-tartrate) is a novel selective sigma receptor ligand,
      currently being developed for the treatment of schizophrenia. MS-377 showed anti
      phencyclidine (PCP), anti-dopaminergic and anti-serotonergic activities, and we
      anticipated that the anti-psychotic activities of MS-377 were associated with
      sigma(1) receptors. However, its pharmacological profile is partly distinct from
      those of selective sigma(1) receptor ligands. Thus, one of the possible
      speculations is that MS-377 has another site of action. In the present study, we
      examined the binding properties of radiolabeled MS-377 ([3H]MS-377) to rat brain
      membranes. [3H]MS-377 showed saturable and reversible binding to rat brain
      membranes. Scatchard plot and Hill plot from saturation studies were linear, with
      K(d) of 15.2+/-6.6 nM, B(max) of 599.4+/-58.6 fmol/mg protein and Hill
      coefficient of 1.01+/-0.01, indicating that [3H]MS-377 bound to a single high
      affinity site in rat brain membranes. Displacement studies revealed that the
      other sigma reference compounds with different structures inhibited the specific
      binding of [3H]MS-377 in a competitive manner. Stereoselectivity was observed for
      the inhibition of [3H]MS-377 binding, (+)-isomers were more potent than (-)
      isomers. Non-sigma receptor ligand PCP showed weak inhibition of [3H]MS-377
      binding. The rank order of potency for the sigma reference compounds to displace
      [3H]MS-377 binding were as following: haloperidol>MS-377=(+)-pentazocine>DTG (1,
      3-Ditolylguanidine)=(-)-pentazocine>BMY14802 (alpha-(4-fluorophenyl)-4-(5-fluoro
      2-pyramidinyl)-1-piperazine butanol)>(+)-SKF-10,047>(-)-SKF-10,047=PCP. These
      results suggested that the MS-377 selectively binds to sigma binding site with
      high affinity in rat brain membranes. Therefore, the anti-psychotic activities of
      MS-377 are attributable to association with sigma(1) receptors.

PMID- 10913585
TI  - Stress-induced hyperthermia in mice: effects of flesinoxan on heart rate and body
      temperature.
AB  - Stress-induced hyperthermia in mice has predictive validity for anxiolytic
      properties of drugs. In this paradigm, 60 min after drug administration rectal
      temperature is measured, which causes hyperthermia of 1-1.5 degrees C (DeltaT) in
      about 10 min. Flesinoxan, a selective 5-HT(1A) receptor agonist with anxiolytic
      like properties, causes hypothermia, which complicates interpretation of stress
      induced hyperthermia. Therefore, we combined flesinoxan treatment and the stress
      paradigm with radiotelemetric measurement of body temperature and heart rate,
      which is also related to anxiety. Subjects were either undisturbed or injected
      with flesinoxan (0-0.1-0.3-1.0 and 3.0 mg/kg), with or without the stress
      paradigm. Flesinoxan (1.0 and 3.0 mg/kg) caused a relatively long-lasting
      hypothermia, but did not lower heart rate. The rectal temperature procedure
      caused hyperthermia and tachycardia. Flesinoxan reduced the stress-induced
      hyperthermia and the tachycardia evoked by the stress procedure. Continuous
      radiotelemetric measurement of heart rate, apart from body temperature, revealed
      that flesinoxan has anxiolytic-like properties in mice.

PMID- 10913586
TI  - Activation of ATP-sensitive K(+) channels: mechanism of peripheral
      antinociceptive action of the nitric oxide donor, sodium nitroprusside.
AB  - Using the rat paw pressure test, in which sensitivity is increased by
      intraplantar injection of prostaglandin E(2) (PGE(2)), we conducted a study using
      several K(+) channel blockers. The objective was to determine what types of K(+)
      channels could be involved in the peripheral antinociceptive action of the nitric
      oxide donor sodium nitroprusside (SNP). SNP elicited a dose-dependent (250 and
      500 microgram/paw) peripheral antinociceptive effect, which was considered local,
      since only higher doses produced an effect in the contralateral paw. The effect
      of SNP (500 microgram/paw) was dose-dependently antagonized by intraplantar
      administration of the sulfonylureas tolbutamide (20, 40 and 160 microgram) and
      glibenclamide (40, 80 and 160 microgram), selective blockers of ATP-sensitive
      K(+) channels. Charybdotoxin (2 microgram/paw), a selective blocker of high
      conductance Ca(2+)-activated K(+) channels, and apamin (10 microgram/paw), a
      selective blocker of low conductance Ca(2+)-activated K(+) channels, did not
      modify the peripheral antinociception induced by SNP. Tetraethylammonium (2
      mg/paw), 4-aminopyridine (200 microgram/paw) and cesium (800 microgram/paw) also
      had no effect. Based on this experimental evidence, we conclude that the
      activation of ATP-sensitive K(+) channels could be the mechanism by which nitric
      oxide, donated by SNP, induces peripheral antinociception, and that Ca(2+)
      activated K(+) channels and voltage-dependent K(+) channels appear not to be
      involved in the process.

PMID- 10913587
TI  - Evaluation of anti-scratch properties of oxatomide and epinastine in mice.
AB  - Anti-scratch effects of oxatomide and epinastine were examined in mice.
      Scratching behavior and cutaneous reactions were induced in BALB/c, ICR and ddY
      mice by dinitrofluorobenzene painting, passive cutaneous anaphylaxis and
      substance P injection, respectively. Although oxatomide and epinastine failed to
      inhibit scratching behavior in BALB/c mice, they inhibited the cutaneous reaction
      significantly. The drugs potently inhibited both scratching behavior and
      cutaneous reaction in ICR mice. They also inhibited scratching behavior and
      cutaneous reaction in ddY mice, although cetirizine and terfenadine failed to
      affect them. Histamine did not induce frequent scratching behavior in BALB/c and
      ddY mice. These results indicate that oxatomide and epinastine inhibit the
      scratching behavior in ICR mice associated with passive cutaneous anaphylaxis
      mainly through an antagonistic action on histamine H(1) receptors. The results
      also indicate that these drugs inhibit substance P-induced scratching behavior in
      ddY mice through an action independent of the antagonistic action on histamine
      H(1) receptors.

PMID- 10913588
TI  - Sildenafil produces antinociception and increases morphine antinociception in the
      formalin test.
AB  - The antinociceptive activity of an inhibitor of phosphodiesterase 5 alone or
      combined with morphine was assessed in the formalin test. Local administration of
      1-[4-ethoxy-3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [3, 4-d]pyrimidin
      5-yl)phenylsulfonyl]-4-methyl piperazine (sildenafil, inhibitor of
      phosphodiesterase 5) produced a dose-dependent antinociceptive effect in the
      second phase of the formalin test in female Wistar rats. In contrast, morphine
      produced antinociception in both phases. Sildenafil significantly increased the
      morphine-induced antinociception. The antinociception produced by the drugs alone
      or combined was due to a local action, as its administration in the contralateral
      paw was ineffective. Pretreatment of the paws with N(G)-L-nitro-arginine methyl
      ester (L-NAME, nitric oxide (NO) synthesis inhibitor), 1H-[1,2, 4]-oxadiazolo[4,3
      a]quinoxalin-1-one (ODQ, guanylyl cyclase inhibitor) or naloxone blocked the
      effect of the combination. Results suggest that opioid receptors, NO and cyclic
      GMP are relevant in the combination-induced antinociception. In conclusion,
      sildenafil produced antinociception and increased that produced by morphine,
      probably through the inhibition of cyclic GMP degradation.

PMID- 10913589
TI  - Antinociceptive effects of Nigella sativa oil and its major component,
      thymoquinone, in mice.
AB  - The antinociceptive effects of Nigella sativa oil and its major component,
      thymoquinone, were examined in mice. The p.o. administration of N. sativa oil (50
      400 mg/kg) dose-dependently suppressed the nociceptive response in the hot-plate
      test, tail-pinch test, acetic acid-induced writhing test and in the early phase
      of the formalin test. The systemic administration (2.5-10 mg/kg, p.o. and 1-6
      mg/kg, i.p.) and the i.c.v. injection (1-4 microgram/mouse) of thymoquinone
      attenuated the nociceptive response in not only the early phase but also the late
      phase of the formalin test. Naloxone injected s.c. (1 mg/kg) significantly
      blocked N. sativa oil- and thymoquinone-induced antinociception in the early
      phase of the formalin test. Moreover, the i.c.v. injection of naloxone (10
      microgram/mouse), the mu(1)-opioid receptor antagonist, naloxonazine (1-5
      microgram/mouse), or the kappa-opioid receptor antagonist, nor-binaltorphimine (1
      5 microgram/mouse), significantly reversed thymoquinone-induced antinociception
      in the early phase but not the late phase of the formalin test, whereas the delta
      opioid receptor antagonist, naltrindole (1-5 ng/mouse, i.c.v.), had no effect on
      either phase. The antinociceptive effect of morphine was significantly reduced in
      thymoquinone- and N. sativa oil-tolerant mice, but not vice versa. These results
      suggest that N. sativa oil and thymoquinone produce antinociceptive effects
      through indirect activation of the supraspinal mu(1)- and kappa-opioid receptor
      subtypes.

PMID- 10913591
TI  - Inotropic effects of OR-1896, an active metabolite of levosimendan, on canine
      ventricular myocardium.
AB  - We performed experiments in dog ventricular trabeculae loaded with aequorin to
      elucidate the mechanism of positive inotropic effect of (R)-N-[4-(4-methyl-6-oxo
      1,4,5, 6-tetrahydro-pyridazin-3-yl)-phenyl]-acetamide (OR-1896), an active
      metabolite of (R)-([4-(1,4,5, 6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]
      hydrazono)-pr opaned initrile (levosimendan). Concentration-response curve for OR
      1896 was biphasic: positive inotropic effect of OR-1896 reached a plateau at 10(
      5) M (1st phase) and the concentration-response curve became steeper at 10(-3) M
      and higher (2nd phase). Maximum response of the 1st phase was 29% of maximal
      response to isoproterenol and associated with an increase in Ca(2+) transients of
      13% of the maximal response to isoproterenol. For a given increase in force, the
      increase in Ca(2+) transients by OR-1896 was lower than that induced by elevation
      of [Ca(2+)](o). The positive inotropic effect of OR-1896 was not associated with
      impairment of relaxation and it was abolished by carbachol. In conclusion, OR
      1896 has a positive inotropic effect partly due to an increase in myofibrillar
      Ca(2+) sensitivity that is exerted via cross-talk with signal transduction
      mediated by cAMP.

PMID- 10913590
TI  - Methamphetamine selectively alters brain glutathione.
AB  - As methamphetamine-induced neurotoxicity has been proposed to involve oxidative
      stress, reduced and oxidized glutathione (GSH and GSSG, respectively), vitamin E
      and ascorbate were measured in the striata of rats killed 2 or 24 h after a
      neurotoxic regimen of methamphetamine. At 2 h, methamphetamine increased GSH and
      GSSG (32. 5% and 43.7%, respectively) compared to controls at 2 h. No difference
      was seen in glutathione at 24 h, and in vitamin E and ascorbate at either time
      point. These findings indicate selectivity of methamphetamine for the glutathione
      system and a role for methamphetamine in inducing oxidative stress.

PMID- 10913592
TI  - Acute hemodynamic effects of insulin-sensitizing agents in isolated perfused rat
      hearts.
AB  - Troglitazone has direct effects on the hemodynamics of the heart. We investigated
      the effects of other insulin-sensitizing agents (rosiglitazone, pioglitazone and
      JTT-501 (4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3, 5
      isoxazolidinedione)) on the hemodynamics of the heart using isolated perfused rat
      hearts. Rosiglitazone significantly decreased heart rate and coronary perfusion
      pressure, and increased peak isovolumic left ventricular pressure, peak rate of
      rise of left ventricular pressure and peak rate of fall of left ventricular
      pressure. The effects of rosiglitazone, however, were milder than those of
      troglitazone. Neither pioglitazone nor JTT-501 had any effect on the heart. D
      alpha-tocopherol, a structural component of troglitazone, did not exert any
      effect on the heart. The coronary vasorelaxant effect of troglitazone and
      rosiglitazone was significantly suppressed by indomethacin, but not by N(omega)
      nitro-L-arginine methyl ester. In conclusion, only rosiglitazone, as well as
      troglitazone, exerted positive inotropic, positive lusitropic, negative
      chronotropic, and coronary vasorelaxant effects on the heart. The coronary
      vasorelaxant effect of troglitazone and rosiglitazone was mediated by
      prostaglandin production.

PMID- 10913593
TI  - Vasopressin receptor subtypes on mesenteric and cremasteric arterioles in rat.
AB  - We studied the effects of a selective vasopressin V(1A) receptor antagonist [1-(1
      (4-(3-acetylaminopropoxy)benzoyl)-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone
      (OPC-21268)] and a selective vasopressin V(2) receptor antagonist [5
      dimethylamino-1(4-(2-methylbenzoylamino)benzoyl)-2,3,4, 5-tetrahydro-1H
      benzazepine (OPC-31260)] on vasopressin-induced contraction of mesenteric and
      cremasteric arterioles in urethane-anaesthetized rats. Vasopressin was infused
      intravenously for 60 min or applied topically to arterioles directly. Vasopressin
      infusion (50, 100 or 500 ng/kg/min) decreased the diameter of both mesenteric and
      cremasteric arterioles. Vasopressin (500 ng/kg/min)-induced vasoconstriction was
      antagonized by OPC-21268 (0. 2, 1.0 and 5.0 mg/kg, i.v.), dose-dependently, but
      not by OPC-31260. Topically applied vasopressin (4.6x10(-10)-4.6x10(-8) M) dose
      dependently constricted both microvessels. Pre-administration of OPC-21268 (5.0
      mg/kg, i.v.) completely inhibited topically applied vasopressin-induced
      vasoconstriction in both microvessels, and OPC-31260 partially inhibited it in
      cremasteric arterioles. These results suggest that vasopressin induces
      vasoconstriction in rat mesenteric and cremasteric arterioles mainly by
      stimulating vasopressin V(1A) receptors, while vasoconstriction in cremasteric
      arterioles is partly associated with stimulation of vasopressin V(2) receptors.

PMID- 10913594
TI  - Are the anti-inflammatory effects of dexamethasone responsible for inhibition of
      the induction of enzymes involved in prostanoid formation in rat carrageenin
      induced pleurisy?
AB  - Since anti-inflammatory steroids modulate multiple gene expression, including the
      expression of prostaglandin H synthase-2 and phospholipase A(2), at the molecular
      level, we studied the effects of dexamethasone on rat carrageenin-induced
      pleurisy to elucidate whether regulation of phospholipase A(2) and prostaglandin
      H synthase-2 expression is the primary mechanism of its anti-inflammatory action.
      Suppression of plasma exudation by a lower dose of dexamethasone (0.3 mg/kg) was
      almost equal to that by aspirin (100 mg/kg), but that by higher dexamethasone
      doses (3 and 30 mg/kg) was considerably stronger, suggesting the involvement of
      effects other than that on prostanoid formation. The lower dose of dexamethasone
      also significantly reduced the pleural exudate neutrophil count and prostanoid
      levels. However, this dose affected neither the prostaglandin H synthase-2 level
      nor the phospholipase A(2) activity in the exudate cells. The prostaglandin H
      synthase-2 level was affected only at the higher doses, while phospholipase A(2)
      activity was not. These results suggest that the anti-inflammatory effects of
      dexamethasone in acute inflammation cannot be ascribed to direct interference
      with prostanoid formation via suppression of phospholipase A(2) and prostaglandin
      H synthase-2 expression.

PMID- 10913595
TI  - Inhibition of nitric oxide by phenylethanoids in activated macrophages.
AB  - Nitric oxide (NO) is one of the pro-inflammatory molecules. Some phenylethanoids
      have been previously shown to possess anti-inflammatory effects. Seven
      phenylethanoids from the stems of Cistanche deserticola, viz. isoacteoside,
      tubuloside B, acteoside, 2'-O-acetylacteoside, echinacoside, cistanoside A and
      tubuloside A, were tested for their effect on NO radical generation by activated
      murine macrophages. At the concentration of 100-200 microM, all the
      phenylethanoids reduced (6.3-62.3%) nitrite accumulation in lipopolysaccharide
      (0.1 microgram/ml)-stimulated J774.1 cells. At 200 microM, they inhibited by 32.2
      72.4% nitrite accumulation induced by lipopolysaccharide (0.1
      microgram/ml)/interferon-gamma (100 U/ml) in mouse peritoneal exudate
      macrophages. However, these compounds did not affect the expression of inducible
      nitric oxide (iNOS) mRNA, the iNOS protein level, or the iNOS activity in
      lipopolysaccharide-stimulated J774.1 cells. Instead, they showed a clear
      scavenging effect (6.9-43.9%) at the low concentrations of 2-10 microM of about
      12 microM nitrite generated from an NO donor, 1-propanamine-3-hydroxy-2-nitroso-1
      propylhydrazino (PAPA NONOate). These results indicate that the phenylethanoids
      have NO radical-scavenging activity, which possibly contributes to their anti
      inflammatory effects.

PMID- 10913596
TI  - Kinetic model of ATP synthase: pH dependence of the rate of ATP synthesis.
AB  - Recently, a novel molecular mechanism of torque generation in the F(0) portion of
      ATP synthase was proposed [Rohatgi, Saha and Nath (1998) Curr. Sci. 75, 716-718].
      In this mechanism, rotation of the c-subunit was conceived to take place in 12
      discrete steps of 30 degrees each due to the binding and unbinding of protons
      to/from the leading and trailing Asp-61 residues of the c-subunit, respectively.
      Based on this molecular mechanism, a kinetic scheme has been developed in this
      work. The scheme considers proton transport driven by a concentration gradient of
      protons across the proton half-channels, and the rotation of the c-subunit by
      changes in the electrical potential only. This kinetic scheme has been analyzed
      mathematically and an expression has been obtained to explain the pH dependence
      of the rate of ATP synthesis by ATP synthase under steady state operating
      conditions. For a single set of three enzymological kinetic parameters, this
      expression predicts the rates of ATP synthesis which agree well with the
      experimental data over a wide range of pH(in) and pH(out). A logical consequence
      of our analysis is that DeltapH and Deltapsi are kinetically inequivalent driving
      forces for ATP synthesis.

PMID- 10913597
TI  - Apoptosis-inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase
      involved in apoptosis.
AB  - Apoptosis-inducing factor (AIF) is encoded by one single gene located on the X
      chromosome. AIF is ubiquitously expressed, both in normal tissues and in a
      variety of cancer cell lines. The AIF precursor is synthesized in the cytosol and
      is imported into mitochondria. The mature AIF protein, a flavoprotein (prosthetic
      group: flavine adenine dinucleotide) with significant homology to plant ascorbate
      reductases and bacterial NADH oxidases, is normally confined to the mitochondrial
      intermembrane space. In a variety of different apoptosis-inducing conditions, AIF
      translocates through the outer mitochondrial membrane to the cytosol and to the
      nucleus. Ectopic (extra-mitochondrial) AIF induces nuclear chromatin
      condensation, as well as large scale ( approximately 50 kb) DNA fragmentation.
      Thus, similar to cytochrome c, AIF is a phylogenetically old, bifunctional
      protein with an electron acceptor/donor (oxidoreductase) function and a second
      apoptogenic function. In contrast to cytochrome c, however, AIF acts in a caspase
      independent fashion. The molecular mechanisms via which AIF induces apoptosis are
      discussed.

PMID- 10913598
TI  - States and transitions during forced unfolding of a single spectrin repeat.
AB  - Spectrin is a vital and abundant protein of the cytoskeleton. It has an elongated
      structure that is made by a chain of so-called spectrin repeats. Each repeat
      contains three antiparallel alpha-helices that form a coiled-coil structure.
      Spectrin forms an oligomeric structure that is able to cross-link actin
      filaments. In red cells, the spectrin/actin meshwork underlying cell membrane is
      thought to be responsible for special elastic properties of the cell. In order to
      determine mechanical unfolding properties of the spectrin repeat, we have used
      single molecule force spectroscopy to study the states of unfolding of an
      engineered polymeric protein consisting of identical spectrin domains. We
      demonstrate that the unfolding of spectrin domains can occur in a stepwise
      fashion during stretching. The force-extension patterns exhibit features that are
      compatible with the existence of at least one intermediate between the folded and
      the completely unfolded conformation. Only those polypeptides that still contain
      multiple intact repeats display intermediates, indicating a stabilisation effect.
      Precise force spectroscopy measurements on single molecules using engineered
      protein constructs reveal states and transitions during the mechanical unfolding
      of spectrin. Single molecule force spectroscopy appears to open a new window for
      the analysis of transition probabilities between different conformational states.

PMID- 10913599
TI  - High-conductance channel induced by the interaction of phage lambda with its
      receptor maltoporin.
AB  - Bacteriophage lambda that binds to liposomes bears its receptor maltoporin (LamB)
      and is able to inject its DNA into the internal space. During this process, the
      liposomes are permeabilized, suggesting that a transmembrane channel has formed
      (Roessner and Ihler (1986) J. Biol. Chem. 261, 386-390). This pore possibly
      constitutes the pathway used by lambda DNA to cross the membrane. We
      reconstituted purified LamB from Shigella in liposomes that were incubated with
      lambda phages. Addition of this mixture to a bilayer chamber resulted in the
      incorporation in planar bilayers of high-conductance channels whose conductance,
      kinetics and voltage dependence were totally different from those of maltoporin
      channels.

PMID- 10913600
TI  - Mitochondrial Isa2p plays a crucial role in the maturation of cellular iron
      sulfur proteins.
AB  - The assembly of iron-sulfur (Fe/S) clusters in a living cell is mediated by a
      complex machinery which, in eukaryotes, is localised within mitochondria. Here,
      we report on a new component of this machinery, the protein Isa2p of the yeast
      Saccharomyces cerevisiae. The protein shares sequence similarity with yeast Isa1p
      and the bacterial IscA proteins which recently have been shown to perform a
      function in Fe/S cluster biosynthesis. Like the Isa1p homologue, Isa2p is
      localised in the mitochondrial matrix as a soluble protein. Deletion of the ISA2
      gene results in the loss of mitochondrial DNA and a strong growth defect.
      Simultaneous deletion of the ISA1 gene does not further exacerbate this growth
      phenotype suggesting that the Isa proteins perform a non-essential function. When
      Isa2p was depleted by regulated gene expression, mtDNA was maintained, but cells
      grew slowly on non-fermentable carbon sources. The maturation of both
      mitochondrial and cytosolic Fe/S proteins was strongly impaired in the absence of
      Isa2p. Thus, Isa2p is a new member of the Fe/S cluster biosynthesis machinery of
      the mitochondrial matrix and may be involved in the binding of an intermediate of
      Fe/S cluster assembly.

PMID- 10913601
TI  - The heterotrimeric Thermus thermophilus Asp-tRNA(Asn) amidotransferase can also
      generate Gln-tRNA(Gln).
AB  - Thermus thermophilus strain HB8 is known to have a heterodimeric aspartyl
      tRNA(Asn) amidotransferase (Asp-AdT) capable of forming Asn-tRNA(Asn) [Becker,
      H.D. and Kern, D. (1998) Proc. Natl. Acad. Sci. USA 95, 12832-12837]. Here we
      show that, like other bacteria, T. thermophilus possesses the canonical set of
      amidotransferase (AdT) genes (gatA, gatB and gatC). We cloned and sequenced these
      genes, and constructed an artificial operon for overexpression in Escherichia
      coli of the thermophilic holoenzyme. The overproduced T. thermophilus AdT can
      generate Gln-tRNA(Gln) as well as Asn-tRNA(Asn). Thus, the T. thermophilus tRNA
      dependent AdT is a dual-specific Asp/Glu-AdT resembling other bacterial AdTs. In
      addition, we observed that removal of the 44 carboxy-terminal amino acids of the
      GatA subunit only inhibits the Asp-AdT activity, leaving the Glu-AdT activity of
      the mutant AdT unaltered; this shows that Asp-AdT and Glu-AdT activities can be
      mechanistically separated.

PMID- 10913603
TI  - Primary structure and expression of peroxisomal acetylspermidine oxidase in the
      methylotrophic yeast Candida boidinii.
AB  - Acetylspermidine oxidase (ASOD) belongs to a family of FAD-containing amine
      oxidases and catalyzes the oxidation of N-acetylated spermidine in polyamine
      metabolism. ASOD was purified to apparent homogeneity from cells of the
      methylotrophic yeast Candida boidinii grown on spermidine as the sole nitrogen
      source. C. boidinii ASOD catalyzed the oxidation of only N(1)-acetylspermidine.
      Based on partial amino acid sequences, oligonucleotide primers were designed for
      polymerase chain reaction, and the ASOD-encoding gene, ASO1, was cloned. The open
      reading frame encoding ASO1 was 1530 bp long and corresponded to a protein of 509
      amino acid residues (calculated molecular mass=57167 Da). ASO1 contained a FAD
      binding motif of G-A-G-I-A-G in the N-terminal region and carried an amino acid
      sequence of -S-K-L at the C-terminal, representing a typical peroxisome targeting
      signal 1. ASOD was localized in the peroxisomes in overexpressed C. boidinii. To
      our knowledge, this is the first report on the gene coding for ASOD that can
      catalyze the oxidation of N-acetylated polyamine as a substrate, from any type of
      organism.

PMID- 10913604
TI  - Covalent binding of ATPgammaS to the nucleotide-binding site in S14C-actin.
AB  - We have recently reported on the characterization of beta-actin carrying the
      mutation S14C in one of the phosphate-binding loops. The present paper describes
      the attachment of the adenosine 5'-[gamma-thio]-triphosphate (ATPgammaS) to actin
      containing this mutation. Treatment of S14C-actin with ATPgammaS blocked further
      nucleotide exchange and raised the thermal stability of the protein, suggesting
      the formation of a covalent bond between the sulfhydryl on the terminal phosphate
      of ATPgammaS and cysteine-14 of the mutant actin. The affinity of the derivatized
      G-actin for DNase I as compared to wild-type ATP-actin was lowered to a similar
      extent as that of ADP.AlF(4)-actin. The derivatized actin polymerized slower than
      ATP-actin but faster than ADP-actin. Under these conditions the bound ATPgammaS
      was hydrolyzed, suggesting the formation of a state corresponding to the
      transient ADP.P(i)-state. ATPgammaS-actin interacted normally with profilin,
      whereas the interaction with actin depolymerizing factor (ADF) was disturbed, as
      judged on the effects of these proteins on actin polymerization.

PMID- 10913602
TI  - ATP-dependent regulation of nuclear Ca(2+) levels in plant cells.
AB  - Localised alterations in cytoplasmic Ca(2+) levels are an integral part of the
      response of eukaryotic cells to a plethora of external stimuli. Due to the large
      size of nuclear pores, it has generally been assumed that intranuclear Ca(2+)
      levels reflect the prevailing cytoplasmic Ca(2+) levels. Using nuclei prepared
      from carrot (Daucus carota L.) cells, we now show that Ca(2+) can be transported
      across nuclear membranes in an ATP-dependent manner and that over 95% of Ca(2+)
      is accumulated into a pool releasable by the Ca(2+) ionophore A.23187. ATP
      dependent nuclear Ca(2+) uptake did not occur in the presence of ADP or ADPgammaS
      and was abolished by orthovanadate. Confocal microscopy of nuclei loaded with
      dextran-linked Indo-1 showed that the initial ATP-induced rise in [Ca(2+)] occurs
      in the nuclear periphery. The occurrence of ATP-dependent Ca(2+) uptake in plant
      nuclei suggests that alterations of intranuclear Ca(2+) levels may occur
      independently of cytoplasmic [Ca(2+)] changes.

PMID- 10913605
TI  - Type Ialpha phosphatidylinositol 4-phosphate 5-kinase is a putative target for
      increased intracellular phosphatidic acid.
AB  - Despite the fact that phosphatidic acid (PtdOH) has been implicated as a lipid
      second messenger for nearly a decade, its intracellular targets have remained
      unclear. We sought to investigate how an increase in the level of PtdOH could
      modulate phosphatidylinositol 4-phosphate 5-kinase (PIPkin), an enzyme involved
      in phosphatidylinositol 4,5-bisphosphate synthesis. Transfection of porcine
      aortic endothelial (PAE) cells with haemagglutinin (HA)-tagged type Ialpha PIPkin
      followed by immunofluorescence confocal microscopy revealed the enzyme to be
      localised to the plasma membrane. When the transfected PAE cells were stimulated
      with lyso-PtdOH, increased PIPkin activity was found to be associated with HA
      immunoprecipitates in an in vitro assay. This PIPkin activation was found to be
      greatly reduced by prior treatment of the cells with 1-butanol, thereby
      implicating phospholipase D (PLD) as the in vivo generator of PtdOH. In order to
      determine if the PtdOH-dependent activation of type Ialpha PIPkin was dictated by
      a specific molecular composition of PtdOH, the wild type murine and porcine alpha
      isoforms of diacylglycerol kinase (DGK) were individually co-transfected along
      with type Ialpha PIPkin. Under these conditions an increase in type Ialpha PIPkin
      lipid kinase activity was found in HA immunoprecipitates in an in vitro assay. No
      increases in lipid kinase activity were observed when type Ialpha PIPkin was co
      transfected with either the human DGKepsilon isoform or a kinase-dead mutant of
      the murine DGKalpha isoform. These results provide the first direct evidence for
      the unification of the production of saturated/monounsaturated PtdOH (through two
      different routes, PLD and DGK) and the in vivo activation of type Ialpha PIPkin
      by this lipid second messenger.

PMID- 10913606
TI  - Urokinase-type plasminogen activator up-regulates the expression of its cellular
      receptor.
AB  - The expression of the receptor for the urokinase-type plasminogen activator
      (uPAR) can be regulated by several hormones, cytokines, tumor promoters, etc.
      Recently, it has been reported that uPAR is capable of transducing signals, even
      though it is lacking a transmembrane domain and a cytoplasmatic tail. We now
      report that uPAR cell surface expression can be positively regulated by its
      ligand, uPA, in thyroid cells. The effect of uPA is independent of its
      proteolytic activity, since inactivated uPA or its aminoterminal fragment have
      the same effects of the active enzyme. The increase of uPAR on the cell surface
      correlates with an increase of specific uPAR mRNA. Finally, uPA up-regulates uPAR
      expression also in other cell lines of different type and origin, thus suggesting
      that the regulatory role of uPA on uPAR expression is not restricted to thyroid
      cells, but it occurs in different tissues, both normal and tumoral.

PMID- 10913608
TI  - Effect of DNA topology on plasmid DNA repair in vivo.
AB  - Escherichia coli nucleotide excision repair (NER) is responsible for removing
      bulky DNA adducts by dual incisions of the UvrABC endonuclease. Although the
      activity of the UvrAB complex which can induce DNA conformational change is
      employed in NER, the involvement of DNA topology and DNA topoisomerases remains
      unclear. We examined the effect of topoisomerase inhibitions on a NER in vivo
      system. The repair analysis of intracellular plasmid revealed that the DNA damage
      on positive supercoils generated by gyrase inhibition remained unrepaired,
      whereas the DNA damage was repaired in topoisomerase I mutants. These results
      suggest that DNA topology affects the NER process and the removal of positive
      supercoils by gyrase is vital for the efficiency of the E. coli NER system.

PMID- 10913609
TI  - Odorant and pheromone binding by aphrodisin, a hamster aphrodisiac protein.
AB  - Aphrodisin is a soluble glycoprotein of hamster vaginal discharges, which
      stimulates male copulatory behavior. Natural aphrodisin was purified and its post
      translational modifications characterized by MALDI-MS peptide mapping. To
      evaluate its ability to bind small volatile ligands, the aphrodisiac protein was
      expressed in the yeast Pichia pastoris as two major isoforms differing in their
      glycosylation degree, but close in conformation to the natural protein. Dimeric
      recombinant aphrodisins were equally able to efficiently bind odors (2-isobutyl-3
      methoxypyrazine and methyl thiobutyrate) and a pheromone (dimethyl disulfide),
      suggesting that they could act as pheromone carriers instead of, or in addition
      to, direct vomeronasal neuron receptor activators.

PMID- 10913607
TI  - Blue light regeneration of bacteriorhodopsin bleached by continuous light.
AB  - Photobleaching of bacteriorhodopsin (BR) by continuous light has recently been
      demonstrated. This bleaching consists of at least two subsequent product states.
      One of them is absorbing maximally in the blue spectral region. Our present study
      shows that upon illumination of the bleached sample with blue light a back
      photoprocess appears, resulting in regeneration of the original BR state. From a
      technical point of view, the observed phenomenon is similar to the reverting
      effect of blue light on the photocycle. An important difference is that the
      photobleached state of BR is much more stable than any of the photocycle
      intermediates, and may provide an advantage for several technical applications.

PMID- 10913610
TI  - Inversion of the anomeric configuration of the transferred sugar during
      inactivation of the macrolide antibiotic oleandomycin catalyzed by a macrolide
      glycosyltransferase.
AB  - Macrolides are a group of antibiotics structurally characterized by a macrocyclic
      lactone to which one or several deoxy-sugar moieties are attached. The sugar
      moieties are transferred to the different aglycones by glycosyltransferases
      (GTF). The OleI GTF of an oleandomycin producer, Streptomyces antibioticus,
      catalyzes the inactivation of this macrolide by glycosylation. The product of
      this reaction was isolated and its structure elucidated. The donor substrate of
      the reaction was UDP-alpha-D-glucose, but the reaction product showed a beta
      glycosidic linkage. The inversion of the anomeric configuration of the
      transferred sugar and other data about the kinetics of the reaction and primary
      structure analysis of several GTFs are compatible with a reaction mechanism
      involving a single nucleophilic substitution at the sugar anomeric carbon in the
      catalytic center of the enzyme.

PMID- 10913611
TI  - Role of the histidine residues of visna virus nucleocapsid protein in metal ion
      and DNA binding.
AB  - Zinc finger (ZF) domains in retroviral nucleocapsid proteins usually contain one
      histidine per metal ion coordination complex (Cys-X(2)-Cys-X(4)-His-X(4)-Cys).
      Visna virus nucleocapsid protein, p8, has two additional histidines (in the
      second of its two ZFs) that could potentially bind metal ions. Absorption spectra
      of cobalt-bound ZF2 peptides were altered by Cys alkylation and mutation, but not
      by mutation of the extra histidines. Our results show that visna p8 ZFs involve
      three Cys and one His in the canonical spacing in metal ion coordination, and
      that the two additional histidines appear to interact with nucleic acid bases in
      p8-DNA complexes.

PMID- 10913612
TI  - Kinetic analysis of the reaction catalyzed by chitinase A1 from Bacillus
      circulans WL-12 toward the novel substrates, partially N-deacetylated 4
      methylumbelliferyl chitobiosides.
AB  - The kinetic behavior of chitinase A1 from Bacillus circulans WL-12 was
      investigated using the novel fluorogenic substrates, N-deacetylated 4
      methylumbelliferyl chitobiosides [GlcN-GlcNAc-UMB (2), GlcNAc-GlcN-UMB (3), and
      (GlcN)(2)-UMB (4)], and the results were compared with those obtained using 4
      methylumbelliferyl N, N'-diacetylchitobiose [(GlcNAc)(2)-UMB (1)] as the
      substrate. The chitinase did not release the UMB moiety from compound 4, but
      successfully released UMB from the other substrates. k(cat)/K(m) values
      determined from the releasing rate of the UMB moiety were: 145.3 for 1, 8.3 for
      2, and 0.1 s(-1) M(-1) for 3. The lack of an N-acetyl group at subsite (-1)
      reduced the activity to a level 0.1% of that obtained with compound 1, while the
      absence of the N-acetyl group at subsite (-2) reduced the relative activity to
      5.7%. These observations strongly support the theory that chitinase A1 catalysis
      occurs via a 'substrate-assisted' mechanism. Using these novel fluorogenic
      substrates, we were able to quantitatively evaluate the recognition specificity
      of subsite (-2) toward the N-acetyl group of the substrate sugar residue. The (
      2) subsite of chitinase A1 was found to specifically recognize an N-acetylated
      sugar residue, but this specificity was not as strict as that found in subsite (
      1).

PMID- 10913613
TI  - The involvement of p38 mitogen-activated protein kinase in the alpha-melanocyte
      stimulating hormone (alpha-MSH)-induced melanogenic and anti-proliferative
      effects in B16 murine melanoma cells.
AB  - Activation of p38 or p44/42 mitogen-activated protein (MAP) kinases has been
      shown to trigger differentiation in a number of cell types. The present study has
      investigated the roles of these kinases in the alpha-melanocyte stimulating
      hormone (alpha-MSH)-induced melanogenic and proliferative responses in B16
      melanoma cells. Treatment of cells with alpha-MSH led to the time-dependent
      phosphorylation of both p38 and p44/42 MAP kinases. However, only inhibition of
      p38 MAP kinase activity with SB 203580 blocked both the alpha-MSH-induced
      melanogenic and anti-proliferative effects. It therefore appears that activation
      of the p38 pathway can promote melanogenesis and inhibit growth of B16 melanoma
      cells.

PMID- 10913615
TI  - Plant heterotrimeric G protein beta subunit is associated with membranes via
      protein interactions involving coiled-coil formation.
AB  - Gbeta subunits from animals are anchored to membranes via Ggamma subunits. No
      Ggamma has been identified in plants to date. Using differential centrifugation
      of Arabidopsis and broccoli extracts, Gbeta was highly enriched in the microsomal
      pellet. Treatment of microsomes with detergents and salts indicates that plant
      Gbeta is located at the membrane surface and attached to membranes by hydrophobic
      interactions. Analysis of transgenic plants expressing Gbeta-GFP fusion proteins
      showed that mutations in the heptad repeat domain of Gbeta severely diminished
      their membrane association. We propose that plant Gbeta is anchored to membranes
      by an unknown protein similar to animal Gbeta by Ggamma, via coiled-coil
      formation.

PMID- 10913614
TI  - Decreased expression of the gut-enriched Kruppel-like factor gene in intestinal
      adenomas of multiple intestinal neoplasia mice and in colonic adenomas of
      familial adenomatous polyposis patients.
AB  - Gut-enriched Kruppel-like factor (GKLF) is a zinc finger-containing transcription
      factor, the expression of which is associated with growth arrest. We compared
      Gklf expression in intestinal and colonic adenomas to normal mucosa in multiple
      intestinal neoplasia (Min) mice and familial adenomatous polyposis (FAP)
      patients, respectively, using semi-quantitative RT-PCR. In Min mice, the level of
      Gklf transcript is highest in normal-appearing intestinal tissues and decreases
      as the size of the adenoma increases. In FAP patients, the level of GKLF
      transcript is lower in adenomas compared to paired normal-appearing mucosa from
      the same patient or normal colonic mucosa from control individuals without FAP.
      The possibility of DNA methylation as a cause for the decreased expression of
      Gklf in adenomas of Min mice was investigated by methylation-specific PCR.
      Results indicate that the Gklf gene is not methylated in either normal or
      tumorous tissues. The findings of our study are therefore consistent with the
      potential role of GKLF as a negative growth regulator of gut epithelial cells.

PMID- 10913616
TI  - Flavones and flavonols at dietary levels inhibit a transformation of aryl
      hydrocarbon receptor induced by dioxin.
AB  - Dioxins invade the body mainly through the diet, and produce toxicity through the
      transformation of aryl hydrocarbon receptor (AhR). An inhibitor of the
      transformation should therefore protect against the toxicity and ideally be part
      of the diet. We examined flavonoids ubiquitously expressed in plant foods as one
      of the best candidates, and found that the subclasses flavones and flavonols
      suppressed antagonistically the transformation of AhR induced by 1 nM of 2,3,7,8
      tetrachlorodibenzo-p-dioxin, without exhibiting agonistic effects that transform
      AhR. The antagonistic IC(50) values ranged from 0.14 to 10 microM, close to the
      physiological levels in human.

PMID- 10913618
TI  - Probing sugar translocation through maltoporin at the single channel level.
AB  - Sugar permeation through maltoporin of Escherichia coli, a trimer protein that
      facilitates maltodextrin translocation across outer bacterial membranes, was
      investigated at the single channel level. For large sugars, such as maltohexaose,
      elementary events of individual sugar molecule penetration into the channel were
      readily observed. At small sugar concentrations an elementary event consists of
      maltoporin channel closure by one third of its initial conductance in sugar-free
      solution. Statistical analysis of such closures at higher sugar concentrations
      shows that all three pores of the maltoporin channel transport sugars
      independently. Interestingly, while channel conductance is only slightly
      asymmetric showing about 10% higher values at -200 mV than at +200 mV (from the
      side of protein addition), asymmetry in dependence of the sugar binding constant
      on the voltage polarity is about 20 times higher. Combining our data with
      observations made with bacteriophage-lambda we conclude that the sugar residence
      time is much more sensitive to (and is decreased by) voltages that are negative
      from the intra-cell side of the bacterial membrane.

PMID- 10913617
TI  - Role of reactive oxygen species and phosphatidylinositol 3-kinase in
      cardiomyocyte differentiation of embryonic stem cells.
AB  - Cardiotypic development in embryonic stem cell-derived embryoid bodies may be
      regulated by reactive oxygen species (ROS). ROS were generated by a NADPH oxidase
      like enzyme which was transiently expressed during the time course of embryoid
      body development. Incubation with either H(2)O(2) or menadione enhanced
      cardiomyogenesis, whereas the radical scavengers trolox,
      pyrrolidinedithiocarbamate and N-acetylcysteine exerted inhibitory effects. The
      phosphatidylinositol 3-kinase (PI-3-kinase) inhibitors LY294002 and wortmannin
      abolished cardiac commitment and downregulated ROS in embryoid bodies.
      Coadministration of LY294002 with prooxidants resumed cardiomyocyte
      differentiation, indicating a role for PI-3-kinase in the regulation of the
      intracellular redox state.

PMID- 10913619
TI  - Nascent Lep inserts into the Escherichia coli inner membrane in the vicinity of
      YidC, SecY and SecA.
AB  - Targeting and assembly of the Escherichia coli inner membrane protein leader
      peptidase (Lep) was studied using a homologous in vitro targeting/translocation
      assay. Assembly of full-length Lep was efficient in the co-translational presence
      of membrane vesicles and hardly occurred when membranes were added post
      translationally. This is consistent with the signal recognition particle
      dependent targeting of Lep. Crosslinking experiments showed that the hydrophilic
      region P1 of nascent membrane-inserted Lep 100-mer was in the vicinity of SecA
      and SecY, whereas the first transmembrane domain H1 was in the vicinity of YidC.
      These results suggested that YidC, together with the Sec translocase, functions
      in the assembly of Lep. YidC might be a more generic component in the assembly of
      inner membrane proteins.

PMID- 10913620
TI  - Patch-clamp study of liver nuclear ionic channels reconstituted into giant
      proteoliposomes.
AB  - Nuclear ionic channels (NICs) represent ubiquitous structures of living cells,
      although little is known about their functional properties and encoding genes. To
      characterize NICs, liver nuclear membrane vesicles were reconstituted into either
      planar lipid bilayers or proteoliposomes. Reconstitution of nuclear envelope (NE)
      vesicles into planar lipid bilayer proceeded with low efficiency. NE vesicle
      reconstitution into proteoliposomes led to NIC observations by the patch-clamp
      technique. Large conductance, voltage-gated, K(+)-permeant and Cl(-)-permeant
      NICs were characterized. An 80-105-pS K(+)-permeant NIC with conducting sub-state
      was also recorded. Our data establish that NICs can be characterized upon
      reconstitution into giant proteoliposomes and retain biophysical properties
      consistent with those described for native NICs.

PMID- 10913621
TI  - CD44v6 cell surface expression is a common feature of macrophages and macrophage
      like cells - implication for a natural macrophage extravasation mechanism
      mimicked by tumor cells.
AB  - Soluble CD44standard (sCD44s) and CD44v6 (sCD44v6) cannot only be detected in
      sera of patients with pancreatic carcinoma but also of healthy blood donors. To
      investigate whether sCD44s and sCD44v6 are derived from white blood cells, we
      stimulated whole blood with phytohemagglutinin and interleukin-2, which induced
      expression of CD44v6 only on monocytes. For further investigations, we used the
      promyelocytic leukemia cell line Hl-60. Only Hl-60 cells differentiating along
      the macrophage pathway showed increased expression of CD44s and CD44v6.
      Furthermore, only macrophages showed increased secretion of sCD44s and sCD44v6.
      Our data suggest that CD44s and CD44v6 are common adhesion molecules on
      macrophages and macrophage-like cells.

PMID- 10913622
TI  - The adenovirus-2 E1B-55K protein interacts with a mSin3A/histone deacetylase 1
      complex.
AB  - The adenovirus E1B-55K protein is a multifunctional phosphoprotein that regulates
      nuclear to cytoplasmic export of host cell and viral mRNAs during lytic viral
      growth. E1B-55K also blocks apoptosis by binding and functionally inactivating
      the human tumor suppressor protein p53. Here, we show that E1B-55K interacts with
      histone deacetylase 1 (HDAC1) and the transcriptional corepressor protein mSin3A,
      both in the adenovirus-transformed 293 cell line and during a lytic adenovirus
      infection. Furthermore, we show that the central amino acids 156-261 in E1B-55K
      are necessary for efficient HDAC1 interaction. Importantly, the E1B
      55K/mSin3A/HDAC1 complex is also enzymatically active, catalyzing deacetylation
      of a histone substrate peptide. Collectively, our results suggest that E1B-55K
      interaction with mSin3A/HDAC1 containing complexes may be significant for one or
      several of the multiple activities ascribed to this protein.

PMID- 10913624
TI  - Clostridium perfringens enterotoxin binds to the second extracellular loop of
      claudin-3, a tight junction integral membrane protein.
AB  - Claudins (claudin-1 to -18) with four transmembrane domains and two extracellular
      loops constitute tight junction strands. The peptide toxin Clostridium
      perfringens enterotoxin (CPE) has been shown to bind to claudin-3 and -4, but not
      to claudin-1 or -2. We constructed claudin-1/claudin-3 chimeric molecules and
      found that the second extracellular loop of claudin-3 conferred CPE sensitivity
      on L fibroblasts. Furthermore, overlay analyses revealed that the second
      extracellular loop of claudin-3 specifically bound to CPE at the K(a) value of
      1.0x10(8) M(-1). We concluded that the second extracellular loop is the site
      through which claudin-3 interacts with CPE on the cell surface.

PMID- 10913623
TI  - Regulation of iNOS expression and glutathione levels in rat liver by oxygen
      tension.
AB  - Molecular oxygen (O(2)) regulates the expression of a variety of genes. We
      hypothesized that O(2) tension may regulate iNOS expression in rat liver through
      the production of reactive oxygen species (ROS) and the reduction of
      intracellular glutathione (GSH) levels. To investigate this hypothesis, we
      determined the effects of hyperoxia upon iNOS induction (both at the protein and
      mRNA level) and the intracellular concentration of GSH in an isolated in vitro
      perfused rat liver preparation. To study the potential involvement of ROS in the
      intracellular signaling pathway linking changes in oxygen tension to gene
      expression, we repeated these determinations in the presence of the thiol
      antioxidant N-acetyl-L-cysteine (NAC). We found that 95% O(2) tension caused a
      significant induction of the iNOS protein and mRNA levels paralleled by a
      significant fall in intracellular GSH concentration. The addition of NAC (1 mM)
      to the perfusate during hyperoxia blocked the induction of iNOS and restored GSH
      levels. These results indicate that molecular O(2) regulates the expression of
      iNOS in rat liver at the transcriptional level, most likely through the
      production of ROS and the reduction of intracellular GSH levels.

PMID- 10913625
TI  - The activation of eukaryotic initiation factor (eIF)2B by growth factors in PC12
      cells requires MEK/ERK signalling.
AB  - Epidermal and nerve growth factors (EGF and NGF) activate protein synthesis and
      initiation factor eIF2B in rat phaeochromocytoma (PC12) cells. The activation of
      protein synthesis by EGF or NGF depends upon extracellular regulated kinase
      kinase (MEK)/extracellular regulated kinase signalling. Here we show that
      PD98059, an inhibitor of MEK activation, blocks the activation of eIF2B by EGF or
      NGF. It is known that eIF2B activity can be inhibited by phosphorylation at
      Ser535 in its epsilon-subunit by glycogen synthase kinase (GSK)-3. We find that
      inactivation of GSK-3 by EGF or NGF is blocked by PD98059. However, neither EGF
      nor NGF caused a detectable change in phosphorylation of Ser535 of eIF2Bepsilon.
      Thus, the EGF- and NGF-induced activation of eIF2B in PC12 cells involves
      regulatory mechanisms distinct from dephosphorylation of the GSK-3 site.

PMID- 10913626
TI  - Functional Fv fragment of an antibody specific for CD28: Fv-mediated co
      stimulation of T cells.
AB  - The most predominant co-stimulation pathway, which is critical for T cell
      activation and proliferation, is the CD28-B7 pathway. The anti-CD28 monoclonal
      antibody (mAb) also provides a co-stimulatory signal to T cells. In order to
      construct a functional Fv fragment (complex of VH and VL domains) of anti-CD28
      antibody using a bacterial expression system, cDNA encoding the variable regions
      of immunoglobulin from 15E8 hybridoma cells was cloned and expressed in
      Escherichia coli. The Fv fragment was obtained as a soluble protein from the
      periplasmic fraction and showed a binding pattern similar to parental IgG. The Fv
      fragment induced proliferation of peripheral blood mononuclear cells in the
      presence of anti-CD3 or anti-CD2 mAb and enhanced anti-tumor activity of anti
      MUC1x(anti)-CD3 bispecific antibody when tested with lymphokine-activated killer
      cells with T cell phenotype. Thus, the anti-CD28 Fv fragment will be promising
      not only for the study of co-stimulation, but also for cancer immunotherapy.

PMID- 10913627
TI  - Alternative 5'-exons of the mouse cAMP-dependent protein kinase subunit RIalpha
      gene are conserved and expressed in both a ubiquitous and tissue-restricted
      fashion.
AB  - The activity of cAMP-dependent protein kinase is controlled by its regulatory
      subunits. Mouse RIalpha regulatory subunit expression is initiated from five
      different non-coding 5'-regions (exons 1a, 1b, 1c, 1d and 1e). This organization
      appears to be conserved among species. All mouse tissues accumulate exon 1a and
      1b transcripts and most contain more 1b than 1a, except brain, heart and
      oesophagus. Exon 1d and 1e transcripts are found in several tissues, while exon
      1c is testis-specific. All five transcripts are in RIalpha-rich tissues: gonads
      and adrenal glands.

PMID- 10913628
TI  - Reconstitution of yeast microsomal lipid flip-flop using endogenous
      aminophospholipids.
AB  - The molecular basis of transbilayer movement or flipping of phospholipids in the
      endoplasmic reticulum is largely unknown. To circumvent the problems inherent to
      studies with artificial phospholipid analogs, we studied microsomal flip-flop of
      endogenous phosphatidylethanolamine in yeast. The transbilayer transport of
      phosphatidylethanolamine was measured in reconstituted proteoliposomes derived
      from microsomal detergent extracts. Our results demonstrate that flipping is
      protease sensitive but does not require metabolic energy. Our assay is the first
      to use the endogenous substrate of the so-called 'flippase' to study phospholipid
      translocation in endomembranes and may therefore be crucial for the understanding
      of the catalytic properties of this elusive enzyme.

PMID- 10913629
TI  - The GS-GOGAT pathway is not operative in the heterocysts. Cloning and expression
      of glsF gene from the cyanobacterium Anabaena sp. PCC 7120.
AB  - The gene encoding the ferredoxin-dependent glutamate synthase (Fd-GOGAT), glsF,
      from the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120, has been cloned
      and sequenced. Unlike other cyanobacteria, Anabaena 7120 contains only Fd-GOGAT,
      lacking NADH-GOGAT. The amount of glsF transcript and Fd-GOGAT activity were
      similar under all the nitrogen growth conditions tested. Enzyme activity, Western
      and Northern blot analyses indicated that Fd-GOGAT is absent in the heterocysts,
      while glutamine synthetase (GS) and NADP-isocitrate dehydrogenase (IDH) were
      present in these specialised cells. Our results clearly indicate that the GS
      GOGAT pathway is not operative in the heterocysts, and hence glutamate must be
      imported from the adjacent vegetative cells, to sustain GS activity. Heterocysts
      probably export glutamine or another nitrogen rich compound like arginine to the
      vegetative cells.

PMID- 10913630
TI  - Solution structure of alpha-conotoxin SI.
AB  - The nuclear magnetic resonance solution structure of alpha-conotoxin SI has been
      determined at pH 4.2. The 36 lowest energy structures show that alpha-conotoxin
      SI exists in a single major solution conformation and is stabilized by six
      hydrogen bonds. Comparisons are made between the SI solution structure and the
      solution and crystal structures of alpha-conotoxin GI. Surprisingly, a high
      degree of similarity between the backbone conformations of the GI crystal and the
      SI solution structures is seen in the region of lowest sequence homology, namely
      residues Gly-8 to Ser-12. This similarity is more surprising when considering
      that in SI a proline replaces the Arg-9 found in GI. The correspondence in
      conformation in this region provides the definitive evidence that it is the loss
      of the arginine basic charge at residue 9 which determines the differences in
      toxicity between GI and SI, rather than any changes in conformation induced by
      the cyclic proline residue.

PMID- 10913631
TI  - Protein stabilization through phage display.
AB  - RNase S consists of two proteolytic fragments of RNase A, residues 1-20 (S20) and
      residues 21-124 (S pro). A 15-mer peptide (S15p) with high affinity for S pro was
      selected from a phage display library. Peptide residues that are buried in the
      structure of the wild type complex are conserved in S15p though there are several
      changes at other positions. Isothermal titration calorimetry studies show that
      the affinity of S15p is comparable to that of the wild type peptide at 25 degrees
      C. However, the magnitudes of DeltaH(o) and DeltaC(p) are lower for S15p,
      suggesting that the thermal stability of the complex is enhanced. In agreement
      with this prediction, at pH 6, the T(m) of the S15p complex was found to be 10
      degrees C higher than that of the wild type complex. This suggests that for
      proteins where fragment complementation systems exist, phage display can be used
      to find mutations that increase protein thermal stability.

PMID- 10913633
TI  - Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde;
      in vitro analysis with liver subcellular fraction derived from human and Aldh2
      gene targeting mouse.
AB  - A principal pathway of 2-methoxyethanol (ME) metabolism is to the toxic oxidative
      product, methoxyacetaldehyde (MALD). To assess the role of aldehyde dehydrogenase
      (ALDH) in MALD metabolism, in vitro MALD oxidation was examined with liver
      subcellular fractions from Japanese subjects who carried three different ALDH2
      genotypes and Aldh2 knockout mice, which were generated in this study. The
      activity was distributed in mitochondrial fractions of ALDH2*1/*1 and wild type
      (Aldh2+/+) mice but not ALDH2*1/*2, *2/*2 subjects or Aldh2 homozygous mutant
      (Aldh2-/-) mice. These data suggest that ALDH2 is a key enzyme for MALD oxidation
      and ME susceptibility may be influenced by the ALDH2 genotype.

PMID- 10913632
TI  - Splicing before import - an intein in a mitochondrially targeted preprotein folds
      and is catalytically active in the cytoplasm in vivo.
AB  - Nuclear-encoded mitochondrial proteins are cytoplasmically synthesized and
      imported into the organelle. The intein-containing RecA protein of Mycobacterium
      tuberculosis, with or without the CoxIVp mitochondrial targeting signal (MTS),
      was used to determine where a protein targeted to mitochondria folds and becomes
      catalytically active. Analysis of fractions from Saccharomyces cerevisiae cells
      expressing RecA without the MTS revealed that RecA and intein proteins remained
      cytoplasmic. With the MTS, most of RecA was directed to mitochondria, while most
      of the intein remained in the cytoplasm. The intein therefore folds into a
      catalytically active state in the cytoplasm prior to RecA import into
      mitochondria.

PMID- 10913634
TI  - Mutational analysis of the highly conserved C-terminal residues of the XylS
      protein, a member of the AraC family of transcriptional regulators.
AB  - The XylS protein of the TOL plasmid of Pseudomonas putida belongs to the so
      called AraC/XylS family of regulators, that includes more than 100 different
      bacterial proteins. A conserved stretch of about 100 amino acids is present at
      the C-terminal end. This conserved region is believed to contain seven alpha
      helices, including two helix-turn-helix (HTH) DNA binding motifs (alpha(2)-T
      alpha(3) and alpha(5)-Talpha-(6)), connected by a linker alpha-helix (alpha(4)),
      and two flanking alpha-helices (alpha(1) and alpha(7)). The second HTH motif is
      the region with the highest homology in the proteins of the family, with certain
      residues showing almost 90% identity. We have constructed XylS single mutants in
      the most conserved residues and have analysed their ability to stimulate
      transcription from its cognate promoter, Pm, fused to 'lacZ. The analysis
      revealed that mutations in the alpha(5)-helix conserved residues had little
      effect on the XylS transcriptional activity, whereas the distribution of polarity
      in the alpha(6)-helix was important for the activity. The strongest effect of the
      mutations was observed in conserved residues located outside the DNA binding
      domain, namely, Gly-290 in the turn between the two helices, Pro-309 located
      downstream of alpha(6), and Leu-313, in the small last helix alpha(7), that seems
      to play an important role in the activation of RNA-polymerase. Our analysis shows
      that conservation of amino acids in the family reflects structural requirements
      rather than functionality in specific DNA interactions.

PMID- 10913635
TI  - Expression of stem cell factor in pterygium.
AB  - PURPOSE: To investigate the possible role of stem cell factor (SCF) in the
      pathogenesis of pterygium. METHODS: The localization of SCF was examined
      immunohistochemically in excised tissue from 4 primary pterygia and 5 normal
      conjunctival specimens. RESULTS: Three of the four pterygia showed strong
      immunoreactivity of SCF in the subepithelial connective tissue at the cap area.
      This immunoreactivity was completely blocked by using a primary antibody
      preincubated with recombinant SCF. The SCF-positive cells were identified as a
      population of fibroblasts by immunostaining for vimentin and prolyl 4-hydroxylase
      in adjacent sections. No apparent immunoreactivity of SCF was observed in the
      subepithelial connective tissues in the head and body of the pterygia and in the
      normal conjunctiva. CONCLUSION: Stem cell factor is overexpressed in fibroblasts
      at the cap area of most pterygia.

PMID- 10913637
TI  - Treatment parameters for the efficacy of transscleral cyclophotocoagulation in
      rabbits using a diode laser.
AB  - PURPOSE: To determine parameters for the efficacy of transscleral
      cyclophotocoagulation (TSCPC) using a diode laser. METHODS: We performed TSCPC on
      74 pigmented rabbits with different exposure powers and varying number of
      applications, followed by clinical observation and histological examination up to
      24 weeks. RESULTS: Based on observation of the clinical course, the most
      favorable parameters were 600 mW and 36 or 48 applications, which did not cause
      severe complications and sufficiently lowered intraocular pressure (IOP).
      Histological examination revealed coagulation of the epitheliums and stroma of
      the ciliary body at 600 mW. The stroma of the ciliary body was severely damaged
      at 900 mW. CONCLUSIONS: Transscleral cyclophotocoagulation at 600 mW with a
      larger number of applications than previously reported did not cause severe
      complications and effected greater and more lasting lowering of IOP than TSCPC
      with more intense coagulation and fewer applications.

PMID- 10913636
TI  - Comparison of non-tryptophan fluorophores in protein-free extract of brunescent
      and non-brunescent human cataract.
AB  - PURPOSE: To investigate whether any of the fluorophores in the human lens nuclei
      might be responsible for human brunescent cataract formation. METHODS: Human lens
      nuclei (non-brunescent, from 13; brunescent, from 8) were obtained after
      extracapsular cataract extraction in nondiabetic patients. Protein-free extract,
      prepared by filtrating the water-soluble fraction of each nucleus through a
      centrifugal ultrafilter (molecular weight < 5,000), was analytically separated by
      high-performance liquid chromatography. RESULTS: No significant differences
      between non-brunescent and brunescent nuclei were observed in the concentrations
      (mean +/- SD) of 3-hydroxykynurenine O-beta-glucoside (0.67 +/- 0.38 vs. 0.85 +/-
      0. 62 micromol/g wet weight), 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid O
      glucoside (4.1 x 10(5) +/- 2.9 x 10(5) vs. 6.3 x 10(5) +/- 5. 0 x 10(5) area
      unit/g wet weight), and kynurenine (0.016 +/- 0.011 vs. 0.029 +/- 0.021
      micromol/g wet weight). A novel fluorophore that has not been identified so far
      was significantly present more in brunescent than in non-brunescent nuclei
      (brunescent: 1.5 x 10(5) +/- 1.0 x 10(5) vs. non-brunescent: 2.6 x 10(3) +/- 6.3
      x 10(3) area unit/g wet weight, P <.01). Digestion of the protein-free extract
      with beta-glucosidase eliminated the peak corresponding to the novel unidentified
      fluorophore. CONCLUSION: The present results imply a novel protein-unbound
      fluorophore, presumably a beta-glucoside, might possibly be involved in
      brunescent cataract formation.

PMID- 10913638
TI  - Effects of isopropyl unoprostone on rabbit ciliary artery.
AB  - PURPOSE: Isopropyl unoprostone (unoprostone), a prostaglandin F(2 alpha) (PG F(2
      alpha))-related compound, is widely used for treatment of glaucoma in Japan and
      is reported to have effects on ocular circulation. To investigate the action of
      this drug, we have studied the effect of unoprostone on the isolated rabbit
      ciliary artery. METHODS: Under microscopic observation, ciliary arteries were
      prepared from rabbit eyes and mounted in a myograph system. The effects of
      unoprostone on the isolated rabbit ciliary artery were investigated in vitro
      using isometric tension recordings. RESULTS: Exogenously applied PG F(2 alpha)
      but not unoprostone evoked contraction in the rabbit ciliary artery. After
      precontraction with excess-[K](o) solution, unoprostone evoked dose-dependent
      relaxation. The relaxation was not blocked by 10 microM/L N(G)-nitro-L-arginine
      methylester (L-NAME), 1 microM/L 8-37 calcitonin gene-related peptide (8-37 CGRP)
      or 10 microM/L indomethacin. Moreover, unoprostone could induce relaxation even
      in preparations without endothelium. The relaxation induced by diltiazem was
      greater in muscle precontracted in excess-[K](o) solution than that precontracted
      by 10 microM/L histamine. On the other hand, unoprostone induced a similar
      amplitude of relaxation in muscles precontracted by either drug. CONCLUSIONS:
      These results indicate that unoprostone acts directly to relax rabbit ciliary
      artery. The relaxation was not dependent on the endothelium and was not caused by
      intrinsic prostoglandins CGRP, or nitric oxide. Moreover, the relaxation was
      different from that caused by a Ca(2)+ antagonist. The mechanism for this
      relaxation is not yet determined.

PMID- 10913639
TI  - Expression and possible roles of activin A in proliferative vitreoretinal
      diseases.
AB  - PURPOSE: To examine the expression of activin A in eyes and to determine the
      possible functions of activin A in proliferative vitreoretinal diseases. METHODS:
      The activin A concentration in vitreous specimens obtained from eyes with or
      without retinal ischemia was measured by a bioassay using erythroid
      differentiation factor effects of activin A. The expression of activin A and
      activin receptors in the preretinal membranes was observed by immunohistochemical
      analysis. RESULTS: The mean concentration of activin A in the eyes with
      proliferative diabetic retinopathy was 1. 50 +/- 1.27 ng/mL (mean +/- SD; n =
      10), and that in the nondiabetic eyes without retinal ischemia (macular hole and
      epiretinal membrane) was 0.90 +/- 0.55 ng/mL (n = 5). Neither difference was
      significant. Activin A and its receptors were detected in the vascular
      endothelial cells, fibroblast-like cells and round-shaped macrophage-like cells
      in preretinal proliferative membranes by immunohistochemical analysis.
      CONCLUSIONS: Activin A is involved in the proliferative membrane formation in
      both ischemic and nonischemic vitreoretinal proliferative diseases. Activin A, a
      member of TGF-beta superfamily, regulates angiogenesis and tissue fibrosis in the
      wound healing process.

PMID- 10913640
TI  - Effect of topical latanoprost-timolol combined therapy on retinal blood flow and
      circulation of optic nerve head tissue in cynomolgus monkeys.
AB  - PURPOSE: To evaluate the effects of topical latanoprost and timolol in combined
      therapy on retinal blood flow and tissue circulation in the optic nerve head
      (ONH) of the cynomolgus monkey. METHODS: Latanoprost (30 microL, 0.005%) was
      instilled once daily and timolol (30 microL, 0.5%) twice daily for 6 days into 1
      eye, and physiological saline into the other eye to serve as control. Blood
      velocity through retinal veins was determined using Kowa Laser Speckle Blood Flow
      Meter. The ONH tissue blood velocity (NB(ONH)) was determined using the Laser
      Speckle Tissue Circulation Analyzer. Retinal blood flow and NB(ONH)
      determinations were carried out before the first instillation and 4 hours after
      the first instillation on the 2nd experimental day, and the last instillation at
      the same sites at the same time of day. The intraocular pressure (IOP) was also
      measured periodically. RESULTS: After the first instillation, on the 2nd
      experimental day, the retinal blood flow decreased compared with the baseline,
      but 6-day instillation caused no significant change from the baseline. Six-day
      instillation increased the NB(ONH) in the treated eyes by 10% from the baseline
      and by 7% from that in the fellow control eye. After 6-day instillation, the IOP
      was lowered by 7.8+/-2.7 mm Hg and 3.6+/-4.3 mm Hg in the treated and control
      eyes, respectively. CONCLUSIONS: Combined 6-day instillation of latanoprost once
      daily and timolol twice daily has no significant effect on the retinal blood
      flow, but significantly increases the ONH tissue blood velocity in monkey eyes.
      Jpn J Opthalmol 2000;44:227-234

PMID- 10913641
TI  - Nitric oxide synthase expression in ischemic rat retinas.
AB  - PURPOSE: To investigate the expression of nitric oxide synthase (NOS) in the
      ischemic retina. METHODS: Retinal ischemia was induced in rats by bilateral
      common carotid artery occlusion (BCCAO) for various lengths of time. Using the
      retina after BCCAO, expression of neuronal NOS (nNOS) and inducible NOS (iNOS)
      and identification of their positive cells were studied by histological and
      immunohistochemical examinations. RESULTS: Histological examinations revealed
      significant reduction in the thickness of the inner plexiform layer and the outer
      plexiform layer of the retina. Expression of nNOS was detected in retinal
      ganglion cells, amacrine cells, and Muller cells after BCCAO. The expression of
      nNOS and iNOS detected in Muller cells became stronger and persisted long after
      BCCAO. CONCLUSIONS: In the ischemic retina, Muller cells and retinal ganglion
      cells expressed nNOS and iNOS. These phenomena may be involved in the ischemic
      damage to the retina.

PMID- 10913642
TI  - Molecular genetic analysis of ABCR gene in Japanese dry form age-related macular
      degeneration.
AB  - PURPOSE: To explore whether the mutation in the retina-specific ATP-binding
      cassette transporter (ABCR) gene, the Stargardt's disease gene, contributes to
      the prevalence of the dry form of age-related macular degeneration (dry AMD) in
      Japanese unrelated patients. METHODS: Twenty-five Japanese unrelated patients
      with dry AMD who were diagnosed by fluorescein angiography and indocyanine green
      angiography were chosen as the dry AMD group. None of these cases had apparent
      choroidal neovascularization. To detect the mutations in the ABCR gene, genomic
      DNA was extracted from leukocytes of peripheral blood, and 26 exons of the ABCR
      gene were amplified by polymerase chain reaction (PCR). All the PCR products were
      then directly sequenced. When a mutation was detected, the occurrence of a
      mutation was compared between these AMD patients and the control group. RESULTS:
      After direct sequencing, a point mutation in exon 29 was found in one of the 25
      dry AMD patients. In addition, a polymorphism in exon 45 was found in two other
      patients, and three sequence variations in exon 23 were detected in all patients.
      The incidence in AMD patients in whom a mutation in exon 29 (4%) was detected was
      less than that in controls (5%). Screening of the intron-exon boundaries also led
      to the identification of intronic mutation in intron 33. CONCLUSION: In this
      study we found no relationship between allelic variation in the ABCR gene and the
      prevalence of dry AMD in Japanese unrelated patients.

PMID- 10913643
TI  - The relationship between gap-junctional intercellular communication and the
      proliferative activity of retinal pigment epithelial cells.
AB  - PURPOSE: To investigate the relationship between gap-junction mediated
      intercellular communication and the proliferative activity of retinal pigment
      epithelial cells in the retinal tear base. METHODS Retinal tears were created
      experimentally in white rabbits, and the changes of intercellular communication
      via gap junctions between retinal pigment epithelial cells in the retinal tear
      base were investigated using the dye-coupling method, which involves observing
      the spread of a fluorescent dye, Lucifer Yellow CH. In addition, the
      proliferative activity of these cells was investigated using an antibody for
      proliferating cell nuclear antigen and was compared with the changes in
      intercellular communication. RESULTS: Immediately after the creation of retinal
      tears, extensive spreading of Lucifer Yellow CH into adjacent cells was observed,
      which was markedly reduced 1 week later. After 1 month, the spreading of dye to
      adjacent cells was observed again. On the other hand, proliferative activity was
      enhanced at 1 week after retinal tear creation and was reduced again after 1
      month. CONCLUSIONS: It is known that tumor cells with enhanced proliferative
      activity show decreased intercellular communication via gap junctions. The
      present study suggests a possible relationship between intercellular
      communication and the proliferative activity of retinal pigment epithelial cells
      in the base of retinal tears.

PMID- 10913644
TI  - Reproducibility of scanning laser Doppler flowmetry in the rat retina and optic
      nervehead.
AB  - PURPOSE: The purpose of this study is to confirm the reliability of scanning
      laser Doppler flowmetry in the rat retina and optic nervehead, and the validity
      of measuring changes of retinal blood flow in rats while breathing 100% oxygen.
      METHODS: We used a commercially available scanning laser Doppler flowmeter. To
      ascertain reliability, five consecutive and separate perfusion measurements of 12
      eyes of 12 anesthetized pigmented rats were performed. To evaluate the validity
      of the system, repeated measurements were taken in anesthetized rats breathing
      room air or 100% oxygen. This series of measurements was repeated three times.
      RESULTS: The reliability coefficients of volume, flow, and velocity in the optic
      nervehead and the retina ranged from 0.80 to 0.83 and 0. 77 to 0.82,
      respectively. After the first exposure to oxygen, the measured values of volume,
      flow, and velocity were reduced by an average of 20.9-24.0%, 21.2-28.2%, and 19.5
      24.5%, respectively. After the values returned to the basal condition, the second
      and third exposures to oxygen yielded measured values that were reduced by the
      same amounts as at the first exposure. CONCLUSIONS: Scanning laser Doppler
      flowmetry provided relatively good reliability in measurements of blood flow in
      the rat retina and optic nervehead. This study has indicated the possibility of
      applying this system to the rat retina.

PMID- 10913645
TI  - Spontaneous intraocular pressure reduction in normal-tension glaucoma and
      associated clinical factors.
AB  - PURPOSE: To investigate the intraocular pressure (IOP) reduction in certain
      normal-tension glaucoma (NTG) patients and clinical factors associated with this
      reduction. METHODS: Fifty-four NTG patients who met the following enrollment
      criteria were selected: IOP <21 mm Hg during a 24-hour pressure curve and
      throughout the subsequent 12 months; examined every 1 to 4 months for at least 3
      years with no ocular hypotensive therapy. For each patient, the eye with the
      higher mean IOP during the 24-hour pressure curve was selected for this study.
      RESULTS: Six patients had an IOP reduction which was defined as a significant
      decrease (P <.05) of IOP over time, determined by the Spearman rank correlation
      coefficient method. These 6 eyes were rated positive for subsequent IOP
      reduction. The IOP reduction was correlated to clinical factors by means of a
      logistic multiple regression analysis (LOGIST procedure using PC-SAS), which
      demonstrated that the larger difference between the maximum IOP and the minimum
      IOP during the initial 24-hour pressure curve and the absence of disc hemorrhage
      showed significant correlation with IOP reduction (P =.026 and P =.013,
      respectively). The odds ratios were 2.05 per 1 mm Hg increase of difference
      between the maximum IOP and the minimum IOP during the initial 24-hour pressure
      curve and 1.13 for the absence of disc hemorrhage. CONCLUSIONS: The current study
      demonstrated that a significant reduction of IOP over time is not uncommon in NTG
      patients. One ninth of the NTG patients in this study showed a significant IOP
      reduction during a 3-year follow-up period.

PMID- 10913646
TI  - Current trends in cataract and refractive surgery in Japan: 1998 survey.
AB  - PURPOSE: A seventh annual survey was carried out by mail in February 1999 to
      investigate the current trends in cataract and refractive surgery in Japan.
      METHODS: Questionnaires were sent to 925 ophthalmologist members of the Japanese
      Society of Cataract and Refractive Surgery. Data received from 411 (44.4%) of the
      recipients were cross-analyzed and compared with those from the previous surveys.
      RESULTS: In cataract surgery, 93% of respondents preferred phacoemulsification,
      58% employed the self-sealing wound closure technique, and 23% used topical
      anesthesia for phacoemulsification. CONCLUSIONS: There have been trends toward
      more surgical procedures performed by a surgeon, shorter period of
      hospitalization, and increased number of outpatient procedures. In refractive
      surgery, surgeons remained rather conservative; with 26% and 5% of surgeons doing
      astigmatic keratotomy and refractive keratotomy, respectively. Photorefractive
      keratectotomy, laser in situ keratomileusis, phakic intraocular lens, and
      intrastromal corneal ring were judged to be useful refractive surgical procedures
      by 58.2%, 69.5%, 25.4%, and 8. 8% of the respondents, respectively.

PMID- 10913647
TI  - Case report: indocyanine green dye leakage from retinal artery in branch retinal
      vein occlusion.
AB  - BACKGROUND: Little is known about retinal vascular lesions underlying hemorrhage
      in the acute phase of branch retinal vein occlusion (BRVO). CASE: A 64-year-old
      woman presented with a decrease in visual acuity of ten-day duration in her left
      eye. OBSERVATIONS: At the initial examination, her left fundus showed the typical
      appearance of BRVO, including retinal bleeding and soft exudates in the lower
      half of the fundus, after the arteriovenous crossing. Fluorescein angiography
      showed no detail in the retinal vessels, which were occluded by retinal bleeding.
      However, in the early phase of indocyanine green (ICG) angiography, ICG dye
      leaked from the retinal artery at a point proximal to the first bifurcation. In
      the late phase of ICG angiography, the dye pooled along the retinal artery in a
      fusiform fashion. One year after laser photocoagulation was performed in the area
      of the BRVO, ICG dye leakage from the retinal artery had completely disappeared.
      CONCLUSIONS: These findings suggest that the changes in the retina detected by
      ICG angiography may have been associated with the onset of BRVO. In patients with
      acute BRVO, ICG angiography may be used to evaluate retinal arterial lesions
      covered by hemorrhage and provide useful information.

PMID- 10913648
TI  - Indocyanine green angiographic findings in 3 patients with traumatic hypotony
      maculopathy.
AB  - PURPOSE: Little is known about the choroidal circulation in human eyes with
      ocular hypotony. Recently, indocyanine green angiography (IA) became a useful
      method for examining choroidal circulation. The present study using IA was
      designed to determine choroidal circulatory disturbances in patients with
      traumatic hypotony maculopathy. METHODS: Indocyanine green angiography was
      performed on 3 consecutive patients (3 eyes) with traumatic hypotony. One patient
      underwent IA using an infrared fundus camera only during the hypotony stage. The
      other 2 patients underwent IA using a scanning laser ophthalmoscope before and
      after recovery of intraocular pressure (IOP). RESULTS: During the hypotony stage,
      IA revealed multiple hypofluorescent spots in many parts of the fundus, sector
      hypofluorescent areas, dilatation, and tortuosity of the choroidal vessels in the
      posterior pole. These findings had not been detected by fluorescein angiography.
      After surgical treatment, IOP returned to the normal range and visual acuity
      improved. Indocyanine green angiography showed improvement of the sector
      hypofluorescent areas, and dilatation and tortuosity of choroidal vessels in the
      posterior pole. However, most of the hypofluorescent spots and regional delay of
      choroidal filling remained. CONCLUSIONS: Indocyanine green angiography revealed
      that choroidal circulatory disturbances occurred during the hypotony stage and
      that some remained during the recovery stage.

PMID- 10913649
TI  - Familial cases with age-related macular degeneration.
AB  - BACKGROUND: The pathogenesis of age-related macular degeneration (AMD) remains
      unknown. Genetic and environmental factors are thought to be associated with AMD.
      Although some studies have reported familial cases of AMD in the United States,
      as far as we know, familial cases of AMD have rarely been reported in Japan.
      CASES: We describe three families with two members of each family affected with
      AMD and one family with three affected members. OBSERVATIONS: In one family, two
      siblings were affected with AMD with choroidal neovascularization and two other
      siblings had retinal pigment epithelial abnormalities or drusen of the maculas,
      suggesting the heterogeneity of the maculas in the family. However, the other
      families did not show such heterogeneity of the fundus. Among the four families,
      six of nine affected individuals had a smoking habit, a risk factor for AMD.
      CONCLUSIONS: These findings suggest that the development and progression of AMD
      might be associated with genetic factors and environmental factors.

PMID- 10913650
TI  - Analysis of 87 cases with Vogt-Koyanagi-Harada disease.
AB  - PURPOSE: Vogt-Koyanagi-Harada (VKH) disease is known to have varied
      manifestations in different ethnic groups. In order to analyze the clinical
      profile of VKH cases in the Indian population, we studied 87 consecutive cases of
      VKH disease treated in an uveitis clinic in South India between 1985 and 1996.
      METHODS: Retrospective analysis and review of charts of consecutive new VKH cases
      diagnosed in a referral clinic. RESULTS: VKH disease comprised 2.2% of all
      uveitis referrals. Extraocular symptoms or signs were seen in 64% of cases at the
      time of presentation. Most common was meningism (95.9%). However, subsequently
      all patients developed extraocular manifestations. Panuveitis (92%) was the
      commonest presentation. Systemic corticosteroid was the usual form of therapy
      (50.3%) followed by immunosuppressive therapy (39%); surgical treatment was
      needed in 8% of the cases. Complicated cataract (33%) and glaucoma (24%) were
      major complications. Final vision was between 6/60 and 6/18 in 88% of the cases
      and 6/18 and better in 15.4%; there was no improvement in 11% of the cases.
      CONCLUSIONS: VKH disease occurs less frequently in India than in Japan and about
      as commonly as in the United States. Extraocular signs are far less common than
      in the Japanese population. Visual prognosis is good in patients presenting
      within 1 month of onset of symptoms. Immunosuppressive agents and vitreoretinal
      surgery are needed in advanced cases and in cases reported later. Jpn J
      Ophthalmol 2000;44:296-301

PMID- 10913651
TI  - Long-term effects of topical cyclosporine A treatment after penetrating
      keratoplasty.
AB  - PURPOSE: To evaluate the long-term outcome of topical 2% cyclosporine A (CsA)
      treatment as an adjunct to topical corticosteroid treatment of patients after
      penetrating keratoplasty (PKP). METHODS: We reviewed the records of 83 patients
      (86 eyes) who had undergone PKP and received topical CsA treatment
      postoperatively; also the records of 95 PKP patients (97 eyes) who received the
      same treatment, except for the 2% CsA eyedrops, and served as controls. The
      patients were also subdivided into high-risk and low-risk groups. The clinical
      outcome of PKP was evaluated by the rates of graft survival and rejection-free
      graft survival, using the Kaplan-Meier method, and compared with the log-rank
      test. RESULTS: In the high-risk patients, the rejection-free graft survival rate
      was 69.7% in the CsA group and 45.4% in the control group (P =.030), but there
      was no significant difference in the graft survival rate between the two groups.
      CONCLUSION: Topical cyclosporine treatment is effective in reducing the risk of
      allograft rejection in high-risk patients.

PMID- 10913653
TI  - mRNA expression of proto-oncogenes and platelet-derived growth factor in
      proliferative vitreoretinal diseases.
AB  - PURPOSE: To detect the expression of mRNA of protooncogenes ets-1, c-jun, c-fos,
      and platelet-derived growth factor (PDGF) in proliferative membranes of patients
      with proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy
      (PVR). METHODS: cDNA was synthesized from mRNA of proliferative membranes from
      patients with PDR, PVR, premacular fibrosis (PMF), acute retinal necrosis (ARN),
      and age-related macular degeneration (ARMD). Ets-1, c-jun, c-fos, PDGF-A, and
      PDGF-B cDNA were amplified using reverse transcriptase-polymerase chain reaction
      (PCR). RESULTS: Proto-oncogene mRNA was highly expressed in membranes from
      patients with severe PDR, grade D PVR. PDGF mRNA was expressed in almost all
      samples. CONCLUSIONS: Our results suggest that not only PDGF mRNA was expressed
      in the membranes of patients with PDR and PVR, but proto-oncogenes ets-1, c-jun,
      and c-fos mRNA were also expressed.

PMID- 10913652
TI  - Angle-closure glaucoma as a presumed presenting sign in patients with syphilis.
AB  - BACKGROUND: Angle-closure glaucoma is a well-known sequel to syphilitic
      interstitial keratitis. This study describes angle-closure glaucoma in the
      absence of corneal opacity as a presumed presenting sign of syphilis. CASES: Two
      patients presented with angle-closure glaucoma with high peripheral anterior
      synechiae to the level over Schwalbe's line extending the whole circumference of
      the angle. Neither corneal opacity nor aqueous inflammation was present. Diffuse
      or localized retinochoroidal degeneration with pigmentation was found in 1 eye of
      1 patient and in both eyes of the other patient. OBSERVATIONS: Fluorescein
      angiography revealed dotty retinal pigment epithelial damage even in normal
      appearing areas of the fundus. The patients showed a positive test for Treponema
      pallidum hemagglutination and also a low titer of serological tests for syphilis.
      No systemic activity, such as skin rashes, had been noted. CONCLUSIONS: Syphilis
      should be considered in patients presenting high peripheral anterior synechiae
      involving the whole circumference of the angle even in the absence of preceding
      interstitial keratitis.

PMID- 10913654
TI  - The formation and involution of optociliary veins during the course of central
      retinal vein occlusion.
AB  - BACKGROUND: Formation of collateral pathways by veins on the optic nerve head is
      sometimes observed during the resolution of a central retinal vein occlusion
      (CRVO). However, no cases have been reported in which the formation and
      involution of these collateral pathways were documented during the resolution of
      a CRVO. CASE: A 56-year-old man with a nonischemic CRVO was followed over a 10
      year period by ophthalmoscopy, fluorescein angiography (FA), and indocyanine
      green angiography (IA). OBSERVATIONS: Initial examination revealed only mild
      arteriosclerosis and the absence of optociliary veins (OCV) in the right eye.
      Approximately 9 years later, the patient returned with a nonischemic CRVO, and FA
      demonstrated a prolongation of the retinal circulation time to 12.1 seconds
      (normal < 11.0 seconds). Monitoring of this patient while undergoing treatment
      disclosed the development of OCV on the optic nerve head and gradual decrease in
      the retinal hemorrhage. FA showed that the retinal circulation time was
      shortening and recovering to normal. IA verified an outflow through the OCV into
      choroidal veins. Later, ophthalmoscopy showed a narrowing of the diameter of the
      OCV. CONCLUSIONS: We suggest that the OCV developed to drain blood from the
      retinal veins into the vortex veins through choroidal veins to compensate for the
      slowing of retinal blood outflow. The reperfusion of the central retinal vein was
      accompanied by the narrowing of the OCV.

PMID- 10913656
TI  - Genome analysis of adenovirus type 7 and adenovirus type 11
AB  - Purpose: To study the epidemiology of adenovirus type 7 (Ad 7) conjunctivitis and
      adenovirus type 11 (Ad 11) conjunctivitis by determining genome types and
      subgenomic types.Materials and Methods: For Ad 7 I used twelve strains from
      patients with acute viral conjunctivitis and one strain from a patient with
      pneumonia. For Ad 11 I used seventeen strains from patients with cystitis. For Ad
      7 genome typing, I used eleven DNA restriction endonucleases (REs) recognizing 6-
      or 7-base pair sequences and for Ad 11 genome typing, I used seven. For Ad 7 and
      for Ad 11 subgenome typing, I used Taq 1 and Hinf I which recognize 4- or 5-base
      pair sequences.Results: The thirteen Ad 7 strains all belonged to the same genome
      type and subgenome type. Ad 11 strains showed six genome types. Ad 11 p was the
      most frequent strain. Fifteen Ad 11 p strains showed three subgenome types, but
      none of them was the same as the prototype. Conclusions: Ad 7 seems quite stable
      and the Ad 7 epidemic may recur again. On the other hand Ad 11 showed several
      different types. Ad 11 was probably not epidemic in the first half of the 1990s.

PMID- 10913655
TI  - Indocyanine green videoangiography in macular variant of idiopathic polypoidal
      choroidal vasculopathy.
AB  - BACKGROUND: Fifty patients diagnosed with choroidal neovascularization in age
      related macular degeneration were examined by indocyanine green videoangiography.
      Results were correlated with fundus photographs and fluorescein angiograms. Two
      patients were diagnosed with the macular variant of idiopathic polypoidal
      choroidal vasculopathy. CASES: Two middle-aged hypertensive women were diagnosed
      with macular idiopathic polypoidal choroidal vasculopathy. Throughout the follow
      up period, both cases showed improved signs and symptoms without worsening of
      visual acuity, and despite the absence of definitive therapy. OBSERVATIONS:
      Indocyanine green videoangiography demonstrated the characteristic polypoidal
      lesions in idiopathic polypoidal choroidal vasculopathy better than fluorescein
      angiography, particularly when blood, exudates, or pigment epithelial detachments
      blocked visualization of the lesions. CONCLUSIONS: Incidence of idiopathic
      polypoidal choroidal vasculopathy may not be as low as reported, as its
      presentation mimics choroidal neovascularization in age-related macular
      degeneration. Differentiation can be made only through indocyanine green
      videoangiography. Conservative management may be beneficial, as visual prognosis
      is good.

PMID- 10913657
TI  - Clinical and genetic features of choroideremia
AB  - Background: Choroideremia is an X-linked hereditary eye disease that causes
      progressive degeneration of the choroid and retina and frequently leads to legal
      blindness in later life. Recent molecular genetic studies have revealed mutations
      involving the Rab escort protein (REP-1) gene localized at Xq 21.Clinical
      Features: The clinical picture and rate of progression may vary among affected
      individuals in different families and within the same family. Usually, hemizygous
      males develop night blindness in their teenage years, followed by progressive
      peripheral visual field constriction and visual disability in late age.
      Heterozygous female carriers are mostly asymptomatic, but their fundi show
      characteristic pigment changes in the midperiphery closely resembling the fine
      mottling observed in the initial stage of the disease in males.Molecular
      Genetics: Assessment of the REP-1 gene in European and Japanese choroideremia
      patients has revealed a wide variety of mutations, including gross deletions and
      point mutations such as nonsense, frameshift, and splice-site mutations. All
      these mutations are thought to fail in intact REP-1 protein
      synthesis.Conclusions: The recent molecular studies may open a new chapter in the
      research on choroideremia as well as diagnosis and genetic counseling.

PMID- 10913658
TI  - A pathological study on rabbit corneas after laser In situ keratomileusis
AB  - Purpose: To investigate pathological changes in rabbit corneas after laser in
      situ keratomileusis (LASIK).Materials and Methods: We performed LASIK on rabbit
      corneas to theoretically correct 10.0 diopters of myopia. The corneas were
      studied pathologically at day 0, and 3 days, 1 week, 3 weeks, 4 months, and 9
      months after LASIK. Results: At 3 days after LASIK, keratocytes in the ablated
      area changed morphologically into fibroblastic cells. And the structure of
      collagen fibers in the stroma was broken. These changes had disappeared almost
      entirely at 4 months after LASIK. There were no proliferative changes in the
      stroma of the ablated cornea 9 months after LASIK. No significant changes were
      observed in the endothelium. Conclusions: The damage to rabbit corneas induced by
      LASIK was mild to moderate under the present experimental conditions.

PMID- 10913659
TI  - Observation of human corneal and scleral collagen fibrils by atomic force
      microscopy
AB  - Purpose: We attempted to analyze the three-dimensional ultrastructure of human
      corneal and scleral collagen fibrils with an atomic force microscope
      (AFM).Methods: A normal eye removed from a 66-year-old male was used in the
      study. Suspended corneal and scleral collagen fibrils were individually attached
      to glass slides by centrifugation. These collagen fibrils were air-dried and
      observed with a noncontact mode AFM in air.Results: AFM imaging provided
      information on the surface topography of both corneal and scleral collagen
      fibrils. The corneal collagen fibrils had a height of 11.9 +/- 1.0 (mean +/-
      standard deviation) nm and the scleral fibrils of 82.5 +/- 35.6 nm. A periodic
      banding pattern of grooves and ridges was clearly found in both types of fibrils:
      the D-periodicity and the groove depth were 65.7 +/- 0.8 nm and 1.46 +/- 0.50 nm
      in the corneal fibrils, and 67.3 +/- 1.1 nm and 6.16 +/- 1. 23 nm in the scleral
      fibrils.Conclusions: Surface topographic images of human corneal and scleral
      collagen fibrils were clearly obtained with the AFM. This technique provides
      quantitative information on the surface morphology of the collagen fibrils at
      high resolution.

PMID- 10913660
TI  - A new method for quantification of metamorphopsia in patients with epiretinal
      membrane
AB  - Purpose: We have developed a new method for quantification of metamorphopsia and
      applied it to study distorted vision resulting from epiretinal membrane
      (ERM).Patients and Methods: We prepared a modified Amsler chart, which was a
      square grid formed by black lines on a white background with 12 cm on a side and
      divided into 2-cm quadrants. The patients were asked to trace any straight lines
      on the chart which appeared irregular or curved. The length of all lines traced
      by the patients was measured except for the outer frame. The total length of the
      chart itself was 1.200 mm, but it would appear longer in patients with
      metamorphopsia. In addition, the severity of metamorphopsia was scored
      subjectively as follows: 1, absent; 2, slight; 3, mild; 4, moderate; and 5,
      severe. The relationship of the length to the score and to the visual acuity were
      analysed. Sixty-three patients with unilateral ERM were examined.Results: The
      length of the line ranged from 1,200 to 1,259 mm (mean 1,223.3 mm) and was
      correlated significantly to the score. Conclusions: This method might be applied
      usefully in evaluating the severity of metamorphopsia and the surgical outcome of
      eyes with ERM.

PMID- 10913661
TI  - Effect of the consumption of ethanol on the microcirculation of the human optic
      nerve head in the acute phase
AB  - Purpose: The effect of the consumption of ethanol on the circulation of the optic
      nerve head (ONH) in the human eye in the acute phase and its mechanism were
      studied.Methods: Eleven volunteers drank a bottle of beer (633 mL) with or
      without ethanol (29.5 g). Normalized blur (NB), a quantitative index of blood
      flow velocity, was measured in the temporal site of the ONH. NB, blood pressure
      (BP) and pulse rate (PR) were measured before, immediately after, and every 15
      minutes for 90 minutes after consumption. Intraocular pressure (IOP) and plasma
      ethanol concentration were measured before, and 30 and 90 minutes after
      consumption. Genotyping of the aldehyde dehydrogenase (ALDH) 2 gene was also
      performed.Results: NB in the ONH increased significantly from 15 to 45 minutes
      after consumption of ethanol and the maximum increase was 14% at 15 minutes. IOP
      was lowered at 90 minutes after consumption, but it was not significant. Mean BP
      was lowered significantly after 60 minutes. PR and ocular perfusion pressure did
      not change. A significant correlation was found between plasma ethanol
      concentration at 30 minutes and maximum NB. NB in the ALDH 2-deficient group was
      significantly larger from 15 to 45 minutes after consumption than in the
      proficient group.Conclusions: It appeared that the consumption of ethanol can
      increase the blood flow in the human ONH in the acute phase through decreased
      resistance in blood vessels induced by acetaldehyde, a metabolite of ethanol.

PMID- 10913662
TI  - A case of orbital lymphoproliferative lesion diagnosed as malignant lymphoma
      after recurring 11 years later
AB  - Background: Most primary lymphoproliferative lesions in the ocular adnexa,
      including the eyelid, conjunctiva, and orbit, are diagnosed as low-grade
      malignant lymphomas. Recurrence and dissemination of these tumors are rare in
      Japan. The long-term prognosis for this disorder still remains to be
      clarified.Case and Method: A 53-year-old woman was first referred to us for right
      orbital tumor in 1986. After subtotal resection of the tumor, the patient
      received no additional treatment. She visited us in 1997 with the complaint of
      bilateral orbital tumor. Biopsied specimens were examined histologically using
      hematoxylin-eosin and immunohistological staining. Southern blot hybridization
      was used to detect immunoglobulin gene rearrangement. The paraffin-embedded
      specimen obtained in 1986 was also examined for immunoglobulin gene rearrangement
      using nested polymerase chain reaction technique. Findings: The specimens from
      1997 and 1986 were both diagnosed as lymphoid type of inflammatory pseudotumor,
      based on polyclonal B cell immunohistological staining. Immunoglobulin gene
      rearrangement was present in both specimens.Conclusions: The orbital tumor
      resected in 1986 was a low-grade malignant lymphoma which disseminated
      systematically 11 years later. This case shows a long-term course of orbital
      lymphoproliferative lesion with positive immunoglobulin gene rearrangement. It
      also shows the importance of follow-up over 10 years in the case of low-grade
      malignant lymphoma of the ocular adnexa.

PMID- 10913663
TI  - A case of juvenile retinoschisis diagnosed by analysis of the XLRS 1 gene
AB  - Background: We report on a 3-year-old boy who was first diagnosed with retinal
      detachment and macular hole and received surgical treatment. X-linked juvenile
      retinoschisis was determined by DNA analysis.Case: Past or family history was not
      recognized. There was left macular hole but no typical spoke-like foveal
      retinoschisis was observed in either eye. We could not diagnose the case as X
      linked juvenile retinoschisis because there was no family history of it, central
      foveal reflex was observed in the right eye with corrected visual acuity of 1.2,
      and no abnormality was recorded in the electroretinogram. High molecular weight
      DNA was extracted from peripheral leukocytes, and the XLRS 1 gene was analyzed.
      Hemizygous missense mutation, Arg102Gln, was detected. We diagnosed the disease
      as X-linked juvenile retinoschisis because the Arg102Gln mutation was detected in
      a family in Germany, two families in the United Kingdom, and two families in the
      USA.Conclusion: XLRS 1 gene analysis is useful if the diagnosis is difficult
      clinically due to aytpical clinical findings.

PMID- 10913664
TI  - Introduction to genetics in ophthalmology, value of family studies
AB  - This paper reviews the author's personal experience with genetic eye diseases and
      discusses the significance of family studies in providing key information for the
      advancement of molecular research. Choroideremia: This disease has long been
      known as an X-linked progressive tapetoretinal degeneration, but it was first
      described in Japan in 1974 after finding asymptomatic fundus changes in
      heterozygous female carriers that are compatible with X chromosomal inactivation.
      Mutations in the disease-causing gene (REP-1) provide a clue to the diagnosis and
      pathophysiology of the disease.Leber's Hereditary Optic Neuropathy: The clinical
      expression is so variable among affected individuals and families that mild optic
      nerve disease of insidious onset should be differentiated from autosomal dominant
      optic atrophy. Molecular assessment of mitochondrial DNA leads to a definite
      diagnosis of the disease, but mitochondrial DNA mutations do not fully account
      for the clinical manifestation and phenotypic variability of the disease.Norrie
      Disease: This rare X-linked vitreoretinal dysplasia, characterized by congenital
      bilateral blindness, was documented in Japan some twenty years ago and the
      disease has been identified in four unrelated Japanese families. The disease,
      once diagnosed on the basis of elaborate clinical and familial studies, can now
      be defined by molecular assessment of the Norrie disease gene.Congenital
      Nystagmus: A four-generation family was described which presented with autosomal
      dominantly inherited congenital nystagmus, peripheral corneal opacity, and foveal
      hypoplasia without any iris tissue malformation. The diagnosis of this family was
      established by detection of a missense mutation in the paired domain of the PAX 6
      gene, hence conforming to a forme fruste of congenital aniridia.Sorsby's Fundus
      Dystrophy: Two Japanese families with Sorsby's fundus dystrophy showed late-onset
      retinal dystrophy characterized by submacular hemorrhage and atrophy. Our
      patients presented with visual loss as late as 50 years of age or older due to
      macula-confined degenerative changes that were similar in all respects to
      exudative age-related macular degeneration and showed a novel mutation in the
      tissue inhibitor of the metalloproteinases-3 gene.Age-Related Macular
      Degeneration (ARMD): We have studied whether there is any association of
      candidate polymorphic genes involving xenobiotic or antioxidant metabolism with
      susceptibility to ARMD. Preliminary results suggest that the genetic polymorphism
      of microsomal epoxide hydrolase is related to potential risk of ARMD.

PMID- 10913665
TI  - The eye and nutrition
AB  - Purpose: To examine the effect of vitamins and trace elements on ocular
      tissue.Materials and Methods: Rats or mice were fed diets deficient in the trace
      elements Zn, Cu, Mn, Se, Mg, and Cr or in vitamins A, B(12), C, and E. In some
      rats Al and vitamin A were injected in excessive amounts. We studied the
      conjunctiva, cornea, retina, and optic nerve with a light microscope,
      transmission and scanning electron microscopes, an energy dispersive X-ray
      analyzer, and an ion microscope. Histochemical, cytochemical, and
      immunohistochemical techniques were applied to the pathological
      specimens.Results: Deficiencies of Zn, Cu, Mn, and vitamins A, C and E caused a
      loss of goblet cells in the conjunctiva and a prominent decrease of microvilli
      and microplicae in the conjunctiva and cornea. The elements in the goblet cells
      were changed in these conditions. In addition, epithelial cells showed poor
      fibrous development and abnormal distribution of chromatin in the nucleus.Zn, Cu,
      Mn, and vitamins A and E deficiencies caused photoreceptor cells to degenerate
      and disappear. Se deficiency reduced the horizontal and amacrine cells. Vitamin
      B(12) deficiency reduced nerve fibers in the nerve fiber layer of the retina. Mg
      deficiency induced multifocal necrosis in the retinal pigment epithelium and
      apoptotic nuclear changes in the photoreceptor cells. Cr deficiency showed
      abnormal phagocytosis of the photoreceptor outer segment discs in the retinal
      pigment epithelium. Vitamin B(12) was found to be related to the circadian rhythm
      in the retina.Deficiencies of Zn, Cu, Mn, and vitamins A, B(12), and E induced
      degeneration and disappearance of myelin lamellae in the myelinated optic nerve
      fibers.In hypervitaminosis A, lipid droplets appeared in the retinal pigment
      epithelium and alcohol dehydrogenase disappeared in the retinal pigment
      epithelium and photoreceptor outer segments. Excessive Al was toxic to the
      retina, which showed disappearance of photoreceptor cells. Al deposits were seen
      in dendrites and neurons in the outer plexiform layer.Zn seemed to be necessary
      for corneal epithelial cell wound healing.Discussion: Trace elements usually are
      contained in enzymes, which have many metabolic functions. They are related to
      synthesis and breakdown of many substances. Some trace elements such as Zn, Cu,
      Mn, and Se and vitamins including vitamins A, C, and E prevent peroxidation of
      lipids. Some vitamins have an affinity for specific tissues such as epithelial
      cells, nerve fibers, and neuronal cells and are needed for cell differentiation,
      development, and maintenance.Conclusion: Cu, Zn, Mn, Se, Mg, and Cr and vitamins
      A, B(12), C, and E are necessary for maintenance of cellular structure and
      metabolism.

PMID- 10913666
TI  - In vivo measurement of ocular circulation with the laser speckle method
      development of apparatus and application in ophthalmological research
AB  - central retinal vein was 35.5 +/- 3.2 mm/sec with a correlation coefficient
      between them of 0.91. In a total of 4 eyes with impending central retinal vein or
      artery occlusion, measurements by the laser speckle method, and CDI method were
      carried out. The blood velocities measured by the both methods increased along
      with the treatment. A good correlation between the CDI results and the laser
      speckle results indicates validity and clinical potential of the present laser
      speckle method.

PMID- 10913667
TI  - In vivo evaluation of leukocyte dynamics in the retinal and choroidal circulation
AB  - We have developed a new method to visualize leukocytes and evaluate their
      kinetics in the chorioretinal microcirculation of the living eyes. Nuclear
      staining dyes and a scanning laser ophthalmoscope were used to image leukocytes
      in the fundus. Acridine orange was used to visualize leukocytes in the retinal
      microcirculation. For imaging leukocytes in the choroid, indocyanine green was
      injected intravenously. Dynamics of leukocytes in the capillaries of the retina
      and choroid were quantitatively estimated in monkeys and rats. This method also
      allowed evaluation of leukocyte-endothelial interactions, such as rolling or firm
      adhesion, in vivo.Acridine orange leukocyte fluography was used to study
      leukocyte dynamics in the following experimentally induced microcirculatory
      disturbances of the retina: (1) interferon-associated retinopathy, (2) ischemia
      reperfusion injury of the retina, and (3) experimental diabetes mellitus.(1)
      Interferon-associated retinopathySystemic administration of interferon alpha
      enhanced leukocyte-endothelial interactions in the retina, which resulted in
      leukocyte rolling and entrapment in the retinal capillary beds. Leukocyte
      accumulation was also detected in the lung. The entrapment or accumulation of
      leukocytes in the microcirculation was inhibited by simultaneous administration
      of corticosteroids or other agents. These results suggested that leukocytes play
      a major role in the development of adverse effects of interferon, such as
      retinopathy or interstitial pneumonia.(2) Ischemia-reperfusion injury of the
      retinaDuring reperfusion period after transient (60 min) retinal ischemia by
      optic nerve ligation, the rolling of leukocytes in the retinal veins was
      prominent and numerous leukocytes were trapped in the retinal capillaries. The
      number of rolling leukocytes was at a maximum 12 hours after reperfusion.
      Leukocyte entrapment peaked at 24 hours after reperfusion. By blocking adhesion
      molecules on the vascular endothelium, these leukocyte-endothelial interactions
      were effectively inhibited. Postischemic retinal atrophy was also inhibited by
      blocking adhesion molecules. These results suggested that leukocytes may be major
      players in the pathophysiology of ischemia reperfusion injury of the retina.(3)
      Experimental diabetes mellitusLeukocyte dynamics in the retina were studied in
      streptozotocin-induced diabetes and spontaneous diabetes (OLETF rats). In both
      diabetic models, leukocyte entrapment in the retinal capillaries was increased
      even in the early stages of diabetes. Fluorescein angiography revealed that
      trapped leukocytes disturbed the regional capillary blood flow in the downstream.
      Enhanced expression of adhesion molecules was observed in the capillary
      endothelium of the retina in the diabetic rats. Leukocyte entrapment in the
      retinal capillaries might cause microvascular occlusions and dysfunction, in turn
      causing diabetic retinopathy.

PMID- 10913668
TI  - Cell biology of intraocular vascular diseases
AB  - Diabetic retinopathy (DR) still remains the leading cause of blindness in the
      working population of Japan and western world, though therapies such as retinal
      photocoagulation and vitrectomy can be remarkably effective when administered at
      an appropriate stage in the disease process. Consequently, there is a need for
      further investigation of the pathogenesis of DR to develop better therapy. DR is
      characterized by gradually progressive alterations in the retinal
      microvasculature, leading to three fundamental morbidities: (1) vascular
      hyperpermeability, (2) vascular occlusion, and (3) neovascularization. Recent
      studies have revealed that hyperglycemia causes several metabolic disorders which
      cause DR directly or indirectly through the abnormal expression of cytokines
      including vascular endothelial growth factor (VEGF). In this study, we performed
      precise tests of the correlation between intraocular VEGF and the three
      fundamental changes in the diabetic retina mentioned above.Ultrastructural study
      of the human retina revealed that two major pathways are responsible for
      hyperpermeability of diabetic retinal vessels, ie intercellular or paracellular
      transport (opening of the tight junctions) and intracellular or transcellular
      transport (caveolae, intracytoplasmic vesicles, and fenestration). All these
      pathways were induced by intravitreal injection of VEGF. The major trigger of
      VEGF overexpression is tissue ischemia caused by vascular occlusion. However, the
      retinas from the eyes with background DR revealed increased expression of VEGF
      without apparent incidence of vascular occlusion. We have identified accumulation
      of advanced glycation end products (AGEs) in these retinas, and found that AGEs
      are a major stimulus for VEGF overexpression in background DR. Retinal vascular
      occlusion was caused by thrombus formation primarily in the capillary vessels.
      Thrombi mainly consisted of fibrin, platelets, and leucocytes in the early stage
      of their formation, and glial cells and macrophages were also involved in the
      later stage. The blood coagulation process plays an important role in fibrin
      formation in thrombi. The expression of tissue factor (TF), an initiator of
      extrinsic blood coagulation, was upregulated by VEGF in retinal vascular
      endothelial cells (REC). In addition, AGEs were also thrombogenic through the
      induction of TF expression and suppression of the expression of prostacyclin
      stimulating factor (PSF), which stimulate prostacyclin synthesis in vascular
      endothelial cells. These findings suggest that AGEs, VEGF, and TF could interact
      in a vicious circle because AGEs and VEGF could induce retinal vascular occlusion
      which results in further increase in VEGF expression.Intravitreal injection of
      VEGF could induce retinal neovascularization, VEGF stimulates vascular
      endothelial cell proliferation by binding to a specific receptor named kinase
      insert domain-containing receptor/fetal liver kinase (KDR/Flk-1, KDR). AGEs and
      basic fibroblast growth factor (bFGF) induced expression of KDR in REC, and a
      transcription factor Sp 1 was involved in this process. Since the expression of
      KDR as well as VEGF was already upregulated in the retinas with background DR,
      VEGF appeared to start to induce the proliferative changes long before the actual
      onset of proliferative DR. These findings indicated that VEGF and its receptor
      system plays a pivotal role all through the disease process of DR.We considered
      that amelioration of the activated VEGF and its receptor system could lead to the
      development of new therapy for DR. We have developed two novel methods to prevent
      retinal neovascularization by inhibiting VEGF and its receptor system. (1) An
      insulin sensitizing agent (troglitazone) inhibited proliferation, migration, and
      in vitro tube formation by REC as well as oxygen-induced retinal
      neovascularization in a mouse model. Thus, glycemic control by troglitazone could
      reduce the incidence of neovascularization in diabetic eyes. (ABSTRACT TRUNCATED)

PMID- 10913669
TI  - Analysis of the P53, RB/D13S25, and P16 tumor suppressor genes in marginal zone B
      cell lymphoma: An interphase fluorescence in situ hybridization study.
AB  - The genetic mechanisms underlying the genesis, disease progression, and high
      grade transformation of marginal zone B-cell lymphoma (MZBCL) are poorly
      understood. We analyzed 33 cases of histologically and immunophenotypically well
      characterized MZBCL (12 extranodal, 11 nodal, and 10 splenic MZBCL; 27 at primary
      diagnosis and six during the course of disease) by dual-color interphase
      fluorescence in situ hybridization (FISH) for deletions of tumor suppressor
      genes. We investigated loci known to play a role in the genesis or disease
      progression of other subtypes of lymphoid malignancies, namely the P53 gene
      (17p13), the retinoblastoma gene (RB, 13q14), the D13S25 locus (13q14), and the
      P16(INK4A) gene (9p21). Heterozygous deletions of P53 were detected in three out
      of the 33 cases, including two splenic and one extranodal MZBCL. One of these
      patients was analyzed at primary diagnosis and two during the course of disease.
      Heterozygous deletions of the RB gene (nodal MZBCL) and D13S25 (splenic MZBCL)
      were found in one case each. P16 deletions were not detected in any of our cases.
      We conclude that deletions of the analyzed tumor suppressor genes are relatively
      rare in MZBCL, which contrasts with the findings in some other subtypes of NHL.

PMID- 10913670
TI  - Molecular and cytogenetic analysis of lymphoblastoid and colon cancer cell lines
      from cotton-top tamarin (Sagiunus oedipus).
AB  - The cotton-top tamarin (CTT) (Sagiunus oedipus) has been used as an animal model
      to investigate the etiology and pathophysiology of several human diseases,
      including ulcerative colitis and its associated colorectal carcinoma (CRC).
      Little is known, however, about genetic synteny between CTT and humans, and about
      chromosome aberrations in CTT CRC. To address these issues, we have analyzed CTT
      lymphoblastoid and CRC cell lines using cytogenetics, fluorescence in situ
      hybridization (Zoo-FISH), and direct sequencing. The CTT lymphocytes had
      pseudodiploid chromosomes of 46. The CTT CRC cells showed near-diploid
      chromosomes of 45. Several clonal structural aberrations were observed, including
      der(1), a marker chromosome, and double minutes. Zoo-FISH using human chromosome
      2, 3, 5, 6, 9, 11, 13, 15, 16, 17, 19, 22, and X paints identified homologous
      chromosomes and subchromosomal regions in the CTT genome. Fluorescence in situ
      hybridization with human telomeric probe also detected a homologous sequence in
      CTT genome. Direct sequencing of CTT genomic DNA using primers amplifying exons 4
      and 15 of the human APC gene identified DNA sequences in CTT genome with 99% and
      95% homology, respectively. These results provide a basis for further comparative
      studies of CTT and human genome.

PMID- 10913672
TI  - Separation vs. replication of inactive and active centromeres in neoplastic
      cells.
AB  - The inactive centromeres in neoplastic and transformed cells exhibit premature
      separation at prophase or pro-metaphase. The factor(s) that control this behavior
      are not known. Using a human breast cancer cell line, MDA 435, and a transformed
      mouse cell line (L929), we studied the relationship between the sequence of
      centromere separation and the replication of centromeric region associated with
      the active and inactive centromeres. Whereas the inactive centromeres in L929
      cells replicate their pericentric heterochromatin earlier than that associated
      with the active centromeres, those in MDA 435 cells exhibited no strong
      correlation between early separation and replication. A comparison between the
      intragenomic patterns of separation with replication of only active centromeres
      showed that the former is not dependent upon the latter in either L929 cells or
      MDA 435 cells. These studies indicate that, whereas inactive centromeres in
      neoplastic cells separate prematurely in different species, there is no
      uniformity in the control for replication nor does the timing of separation
      depend upon the timing of replication of the centric region.

PMID- 10913671
TI  - Frequent chromosome 8q gains in human small cell lung carcinoma detected by
      arbitrarily primed-PCR genomic fingerprinting.
AB  - The arbitrarily primed-polymerase chain reaction (AP-PCR) genomic fingerprinting
      method was applied to detect chromosomal numerical imbalances in 13 small cell
      lung carcinomas (SCLC). Increases and decreases in the intensity of the AP-PCR
      bands from several chromosomes, representing gains of chromosomes 1, 7, 16, and
      X, and losses of chromosomes 2, 10, and 22, were recurrent events in independent
      tumors. In addition, the most common alterations detected were increases in
      signal intensity of three AP-PCR bands derived from genomic sequences on
      chromosome 8q (eight of 13 tumors: 62%). To define whether the 8q gains observed
      in the AP-PCR analysis include the C-MYC gene at chromosome 8q24 or not, we
      performed targeted AP-PCR analysis of the C-MYC gene. The C-MYC gene was
      amplified in five of the eight tumors with gains of 8q, but in none of the
      remaining five tumors in which 8q gains were not detected. These results indicate
      that chromosome 8q gain occurs frequently in SCLC and gained regions often, but
      do not always, include the C-MYC gene. Moderate increases in copy number of the C
      MYC gene and additional gene(s) in the 8q region appear to be under positive
      selection during SCLC progression.

PMID- 10913673
TI  - Interphase FISH for Y chromosome, VNTR polymorphisms, and RT-PCR for BCR-ABL in
      the monitoring of HLA-matched and mismatched transplants.
AB  - Thirty-six sex-mismatched transplants were studied using fluorescence in situ
      hybridization (FISH) and polymerase chain reaction (PCR) methods. Molecular
      cytogenetics was performed using interphase FISH with a centromeric probe for
      chromosome Y, and PCR amplification was performed with a set of VNTR
      microsatellite loci. In addition, reverse transcriptase-PCR (RT-PCR) for BCR-ABL
      fusion was used to investigate cases of Philadelphia chromosome (Ph)-positive
      chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). Our
      integrated approach of post-transplant monitoring was helpful in documenting
      successful transplants and in controlling the size of Ph-positive clones in CML.
      A striking overlap was found between results from FISH analysis and PCR for
      polymorphic loci.

PMID- 10913674
TI  - High-resolution analysis of chromosome arm 1p alterations in meningioma.
AB  - Loss of heterozygosity (LOH) for loci on chromosome arm 1p is a relatively common
      event in human meningioma, and this anomaly has been proposed to be associated
      with the development of grade II or grade III forms (atypical and anaplastic
      meningiomas). Nevertheless, the limited data available do not allow the
      establishment of the frequency and the extent of the affected 1p regions. To
      determine the status of chromosome 1p in meningiomas, we have performed a
      comprehensive analysis of LOH on 1p in 100 meningiomas using a high density of 1p
      marker loci. Allelic loss was found in 35% of tumors, most corresponding to
      nontypical meningiomas that also displayed losses for loci on chromosome 22.
      Although some tumors displayed complex rearrangements leading to distinct 1p
      deletions, the patterns of loss indicated two main target regions: 1p36 and 1p34
      p32, which represent the most frequently involved regions, whereas 1p22 and
      1p21.1-1p13 regions appeared deleted in some tumors. These results suggest that
      there may be several putative tumor suppressor genes on 1p, the inactivation of
      which may be important in the pathogenesis of meningiomas, as well as in other
      tumor types.

PMID- 10913675
TI  - Silent polymorphisms within the coding region of human sodium/hydrogen exchanger
      isoform-1 cDNA in peripheral blood mononuclear cells of leukemia patients: A
      comparison with healthy controls.
AB  - We have examined the sequence of the cDNA encoding the sodium/hydrogen exchanger
      isoform 1 (NHE1), from 23 bases upstream of the start codon to 28 bases
      downstream of the stop codon. Template was prepared from (1) peripheral blood
      mononuclear cells (PBMC) isolated from 10 healthy unrelated Caucasian volunteers;
      (2) PBMCs isolated from 6 leukemic patients (acute lymphoblastic leukemia [ALL],
      n = 3; chronic lymphocytic leukemia [CLL], n = 1; chronic myelogenous leukemia
      [CML], n = 2); and (3) samples of 4 leukemic cell lines (ALL: CEM, MOLT4; AML:
      KG1a; CML: K562). NHE1 cDNA in normal PBMCs showed silent polymorphism of
      nucleotides 112 (N1: T, frequency 0.70; C, frequency 0.30; prevalence of
      heterozygosity 0.42); 2248 (N2: G, frequency 0.90; A, frequency 0. 10;
      heterozygosity 0.18); and 2493 (N3: G, frequency 0.90; A, frequency 0.10;
      heterozygosity 0.18). Deduced primary structure of NHE1 protein in all normal
      volunteers was identical to that previously published for NHE1 from renal and
      cardiac tissue. Similar to normal PBMCs, NHE1 cDNA from leukemic cells showed
      polymorphism of nucleotides N1, N2, and N3, but failed to demonstrate leukemia
      specific sequence differences. We conclude that the coding region of NHE1 cDNA
      shows a greater level of polymorphism than is currently recognized, but that
      sequence mutation of NHE1 is not a key event in the pathogenesis of leukemia.

PMID- 10913676
TI  - Coordinate deletion of chromosome 3p and 11q in neuroblastoma detected by
      comparative genomic hybridization.
AB  - Neuroblastoma, the most common extracranial solid tumor of childhood, is
      associated with a number of genetic abnormalities that are prognostically
      significant. The most common abnormalities are associated with aggressive
      clinical behavior and include deletion of distal chromosome 1p, NMYC
      amplification, and unbalanced gain of the long arm of chromosome 17. There are
      also other recurrent, but less frequent abnormalities, the clinical significance
      of which is uncertain. These less common abnormalities include deletion 3p, 11q,
      and 14q. To gain further clinical insight into some of the less commonly observed
      abnormalities in neuroblastoma, we performed comparative genomic hybridization
      (CGH) analysis on 24 primary and metastatic neuroblastomas (6 stage 2, 5 stage 3,
      11 stage 4, and 2 stage 4). Nineteen of these tumors were prechemotherapy. A
      total of 190 abnormalities were detected from these tumors. Four of the 24 tumors
      studied showed loss of 11q material, with 3 of these tumors also possessing
      distal chromosome 3p deletions. Our results provide confirmation that deletion of
      chromosome 3p is nonrandomly associated with deletion of chromosome 11q in
      neuroblastoma. However, analysis of our results, along with other results
      reported in the literature, indicate that there is no statistically significant
      association between 3p and 11q loss and more clinically aggressive tumors.

PMID- 10913677
TI  - Genetic characterization of immortalized human prostate epithelial cell cultures.
      Evidence for structural rearrangements of chromosome 8 and i(8q) chromosome
      formation in primary tumor-derived cells.
AB  - We have utilized a combination of conventional and spectral karyotyping (SKY)
      techniques and allelotype analysis to assess numerical and structural chromosome
      alterations in two cell lines derived from normal human prostatic epithelium, and
      three cell lines derived from human prostate primary tumor epithelium,
      immortalized with the E6 and E7 transforming genes of human papilloma virus (HPV)
      16 or the large T-antigen gene of simian virus 40 (SV40). These studies revealed
      trisomy for chromosome 20 and rearrangements involving chromosomes 3, 4, 8, 9,
      10, 16, 17, 18, 19, 21, or 22. In addition, the four HPV-immortalized cell lines
      exhibited extensive duplications or translocations involving the 11q chromosomal
      region. Interestingly, allelotyping data disclosed loss of 8p sequences in two of
      the three primary tumor-derived cell lines, and SKY data revealed that the loss
      of 8p sequences was directly due to i(8q) chromosome formation and/or other
      structural alterations of chromosome 8. This provides intriguing evidence that 8p
      loss in primary human prostate tumors may, in some cases, result from complex
      structural rearrangements involving chromosome 8. Moreover, the data reported
      here provide direct evidence that such complex structural rearrangements
      sometimes include i(8q) chromosome formation.

PMID- 10913678
TI  - Establishment and characterization of a new cell line derived from a human
      primary breast carcinoma.
AB  - A new cell line, designated HDQ-P1, was successfully established from a primary
      ductal infiltrating mammary carcinoma by using a 3T3 feeder layer lethally
      irradiated to 60 Gy. The HDQ-P1 cells have been grown in culture for over 115
      passages and have a doubling time of 60 hours. Characterization of the cell line
      was performed. This included morphology by light and transmission electron
      microscopy, karyotype, growth rate, telomerase expression, tumor antigen
      expression, xenograft implantation into nude mice, colony formation in soft agar,
      TP53 sequencing, and gene copy number of C-MYC, C-ERBB-2, and C-H-RAS oncogenes.
      The epithelial nature of this cell line was confirmed by ultrastructural
      analysis, expression of cytokeratins, and epithelial membrane antigen. The HDQ-P1
      cells possess an extensively rearranged and polyploid karyotype, with an average
      of 20 recurrent marker chromosomes. Scatchard analysis demonstrated that both
      primary tumor and HDQ-P1 cells were estrogen- and progesterone-receptor negative.
      The HDQ-P1 cells had the same expression of human telomerase reverse
      transcriptase as other established breast cancer cell lines such as MDA-MB-231,
      SK-BR-3, and MCF-7. Direct DNA sequencing showed a point mutation which yielded
      to a stop codon at the amino acid 213 in exon 6 of the TP53 gene. A five-fold
      amplification of C-MYC was observed in HDQ-P1 cells. No amplification of C-ERBB-2
      and C-H-RAS genes were observed. This cell line presents unique characteristics
      and may prove to be a good experimental model for investigating breast cancer
      biology.

PMID- 10913679
TI  - Double minutes and c-MYC amplification in acute myelogenous leukemia: Are they
      prognostic factors?
AB  - A case of acute myelogenous leukemia (AML) with double minutes (dmin) and X
      chromosome loss is presented. Using comparative genomic hybridization (CGH), a
      region of high-level DNA amplification was detected at 8q24, the locus of the c
      MYC proto-oncogene. Fluorescence in situ hybridization (FISH) with a DNA probe
      specific for the human c-MYC gene confirmed the extrachromosomal amplification of
      this proto-oncogene in the dmin of the leukemic cells. During the course of the
      disease, three relapses occurred; two complete remissions could be achieved by
      treatment with various chemotherapy regimens. The patient's survival time of 25
      months was considerably longer than in most reported cases of AML with
      extrachromosomal c-MYC amplification. Therefore, the present case challenges the
      view that the occurrence of dmin in AML is generally an indication of poor
      prognosis.

PMID- 10913680
TI  - A PML/RARA chimeric gene on chromosome 2 in a patient with acute promyelocytic
      leukemia (M3) associated with a new variant translocation:
      t(2;15;17)(q21;q22;q21).
AB  - We describe a patient with acute promyelocytic leukemia (APL) carrying a new
      complex variant translocation of t(2;15;17)(q21;q22;q21). The karyotypic
      interpretation was confirmed by fluorescence in situ hybridization (FISH) with
      the use of painting probes of chromosomes 2, 15, and 17 and a PML/RARA dual color
      DNA probe. FISH showed a PML/RARA fusion gene on the der(2) instead of the
      der(15). These results suggest that the critical event in the development of APL
      is the formation of a PML/RARA chimeric gene, regardless of its locus in the
      genome.

PMID- 10913682
TI  - Differential regulation of microglial NO production by protein kinase C
      inhibitors.
AB  - Nitric oxide (NO) produced by microglia has been implicated in the pathogenesis
      of various central nervous system diseases; however, the intracellular signal
      pathways for the production of NO are not well known. Protein kinase C (PKC)
      plays a key role in a variety of signal transduction processes. To elucidate how
      PKC regulates microglial NO production, we examined the effects of PKC inhibitors
      on lipopolysaccharide (LPS)-stimulated NO production by primary cultured rat
      microglia. Staurosporine, a non-selective PKC inhibitor, increased LPS-induced
      production of NO at 0.1-10 nM range of concentration. Protein kinase A (PKA)
      inhibitor, H89, did not affect LPS-induced NO production, suggesting that
      staurosporine effect is not mediated by inhibition of PKA. However, other two PKC
      inhibitors, whose specificities for PKC isoforms were different, Go6976 and Ro-32
      0432, exhibited different effects on NO production from staurosporine; the former
      inhibited and the latter showed no effect. Interestingly, an activator of PKC,
      phorbol 12-myristate 13-acetate (PMA) also increased LPS-induced production of NO
      at 1-10 nM range of concentration, suggesting that prolonged incubation with PMA
      caused down-regulation of PKC. These results indicate that the inhibition or down
      regulation of some PKC isoforms causes the enhancement of NO production. The
      different effects of PKC inhibitors on the NO production suggest that the
      different PKC isoforms play different roles in regulation of NO production in
      microglia.

PMID- 10913684
TI  - Regular exercise improves cognitive function and decreases oxidative damage in
      rat brain.
AB  - The biochemical mechanisms by which regular exercise significantly benefits
      health and well being, including improved cognitive function, are not well
      understood. Four-week-old (young) and 14-month-old (middle aged) Wistar rats were
      randomly assigned to young control and young exercised, middle-aged control and
      middle-aged exercised groups. Exercise groups were exposed to a swimming regime
      of 1 h a day, 5 days a week for 9 weeks. The passive avoidance test showed that
      middle-aged exercised rats had significantly (P<0.05) better short- (24 h) and
      long-term (72 h) memory than aged-matched control rats. Conditioned pole-jumping
      avoidance learning was improved markedly in both age groups by exercise. Brain
      thiobarbituric acid-reactive substances and 8-hydroxy-2'deoxyguanosine content in
      the DNA did not change significantly, while the protein carbonyl levels decreased
      significantly (P<0.05) in both exercised groups. This decrease was accompanied by
      an increase in the chymotrypsin-like activity of proteasome complex in the
      exercised groups, whereas trypsin-like activity did not differ significantly
      between all groups. The DT-diaphorase activity increased significantly (P<0.05)
      in the brain of young exercised animals. These data show that swimming training
      improves some cognitive functions in rats, with parallel attenuation of the
      accumulation of oxidatively damaged proteins.

PMID- 10913683
TI  - Hydrogen peroxide induces rapid digestion of oligodendrocyte chromatin into high
      molecular weight fragments.
AB  - High molecular weight (HMW) fragmentation of nuclear chromatin was studied in
      cultured rat oligodendrocytes (OL) exposed to hydrogen peroxide (H2O2). Intact
      genomic DNA was isolated by agarose embedding, and analyzed by field inversion
      gel electrophoresis, with and without S1 endonuclease digestion to detect and
      discriminate between single and double stranded fragmentations, respectively. The
      exposure of OL to H2O2 resulted in a very rapid degradation of chromosomal DNA
      into HMW fragments that reflect native chromatin structure. Hence, within 10 min
      after the addition of 1 mM H2O2, a discrete pool representing approximately 45%
      of the nuclear chromatin underwent single strand digestion into >400 kb fragments
      likely at AT-rich matrix attachment regions. Subsequent accumulation of single
      stand breaks at these regions led to bifilar scission. Ultimately, chromatin
      within this susceptible pool was cleaved at remaining matrix attachment regions
      into 50-200 kb fragments. Chromatin digestion could be elicited with H2O2
      concentrations as low as 50 microM. After the removal of H2O2, most >400 kb
      fragments were religated within 2 h; however, digestion into 50-200 kb fragments
      was irreversible. The DNA digestion was not accompanied by the degradation of
      nuclear proteins, i.e., lamins A/C and poly (ADP-ribose) polymerase indicating
      that chromatin fragmentation is unlikely to be mediated by proteolysis. In
      conclusion, H2O2 at pathologically relevant concentrations induces a very rapid
      and extensive digestion of OL chromatin into HMW fragments. Because the chromatin
      fragmentation is only partly reversible, it may be a decisive factor in
      committing oxidatively stressed OL to degeneration and/or death.

PMID- 10913685
TI  - Loss of noradrenaline transporter sites in frontal cortex of rats with acute
      (ischemic) liver failure.
AB  - There is increasing evidence that central noradrenaline (NA) transport mechanisms
      are implicated in the central nervous system complications of acute liver
      failure. In order to assess this possibility, binding sites for the high affinity
      NA transporter ligand [3H]-nisoxetine were measured by quantitative receptor
      autoradiography in the brains of rats with acute liver failure resulting from
      hepatic devascularization and in appropriate controls. In vivo microdialysis was
      used to measure extracellular brain concentrations of NA. Severe encephalopathy
      resulted in a significant loss of [3H]-nisoxetine sites in frontal cortex and a
      concomitant increase in extracellular brain concentrations of NA in rats with
      acute liver failure. A loss of transporter sites was also observed in thalamus of
      rats with acute liver failure. This loss of NA transporter sites could result
      from depletion of central NA stores due to a reserpine-like effect of ammonia
      which is known to accumulate to millimolar concentrations in brain in ischemic
      liver failure. Impaired NA transport and the consequent increase in synaptic
      concentrations and increased stimulation of neuronal and astrocytic noradrenergic
      receptors could be implicated in the pathogenesis of the encephalopathy and brain
      edema characteristic of acute liver failure.

PMID- 10913687
TI  - Regulation of chromogranin biosynthesis by neurotrophic growth factors in
      neuroblastoma cells.
AB  - Polypeptide growth factors secreted from the target tissue determine the choice
      of transmitter synthesis in the innervating nerves. We have investigated whether
      they also influence the expression of chromogranins and neuropeptide Y,
      components co-stored with the neurotransmitters within large dense-core vesicles.
      IMR-32 and SH-SY5Y human neuroblastoma cells were treated for up to six days with
      various neurotrophic growth and differentiation factors. For chromogranins A and
      B, no significant changes at the mRNA level were observed and for chromogranin A
      this was confirmed at the protein level. The expression of secretogranin II/pro
      secretoneurin mRNA, however, was considerably enhanced in both cell lines after
      basic fibroblast growth factor treatment. In IMR-32 cells we determined a fast
      and continuous induction, whereas the up-regulation in SH-SY5Y cells was more
      delayed. A transient elevation of secretogranin II/pro-secretoneurin mRNA levels
      was seen in SH-SY5Y cells in response to epidermal growth factor. In these cells
      we also measured the amounts of secretogranin II/pro-secretoneurin protein which
      were increased by both growth factors. In addition to the above described changes
      in secretogranin II/pro-secretoneurin biosynthesis we extended and confirmed data
      available on neuropeptide Y. We found a qualitatively similar pattern of
      biosynthesis regulation as for secretogranin II/pro-secretoneurin, indicating
      that the ultimately increased expression of the two proteins may be
      characteristic of the phenotypic differentiation after growth factor treatment.
      Moreover, this finding of a concomitant regulation further emphasizes the concept
      of secretogranin II/pro-secretoneurin being a neuropeptide precursor from which
      the functional peptide secretoneurin is proteolytically liberated.

PMID- 10913686
TI  - Pharmacology of [3H]R(+)-7-OH-DPAT binding in the rat caudate-putamen.
AB  - Dopamine D3 receptors may be involved in drug addiction and in disorders such as
      schizophrenia and Parkinson's disease. To determine the pharmacological
      properties of dopamine D3 receptors in the rat caudate-putamen, we have
      investigated R(+)-[3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin ([3H]R(+)-7-OH
      DPAT) binding to membrane preparations from the rat caudate-putamen. Kinetic
      analyses showed that [3H]R(+)-7-OH-DPAT binding reached equilibrium in
      approximately 1 h and that both association and dissociation curves were composed
      of at least two components. Likewise, saturation curves showed at least two
      binding components with a combined Bmax value of about 600 fmol/mg protein, which
      is three times higher than what is present in the subcortical limbic area.
      Competition curves were performed with agonists such as R(-)
      propylnorapomorphine, dopamine, PD 128907, quinpirole, and bromocriptine, and
      antagonists such as haloperidol, raclopride, clozapine, GR 218231x, remoxipride,
      and U99194A. These experiments revealed that [3H]R(+)-7-OH-DPAT binding could be
      resolved into three specific binding sites (R1-R3) and one nonspecific binding
      site, with R1-R2 probably representing D3 receptor binding and the minor R3
      representing D2 receptor binding. The low affinities of (+/-)-8-OH-DPAT and 1,3
      di(2-tolyl)guanidine to inhibit [3H]R(+)-7-OH-DPAT binding indicate negligible
      involvement of 5-HT1A or sigma binding sites, respectively. The pharmacological
      profile of [3H]R(+)-7-OH-DPAT (2 nM) binding in the caudate-putamen was similar
      to that of dopamine on [125I]iodosulpride binding in the cerebellar lobule X,
      which contain D3 but not D2 receptors. Mg2+ increased and GTP and Na+ decreased
      the binding of [3H]R(+)-7-OH-DPAT, suggesting a coupling of endogenous D3
      receptors to G proteins. Taken together, these results suggest that dopamine D3
      receptors display multiple agonist binding states, and that D3 receptors are
      present in high concentrations in the rat caudate-putamen. These results may have
      implications for the physiological and pathological roles of dopamine D3
      receptors in the brain.

PMID- 10913689
TI  - Effects of chronic antidepressant treatments on 5-HT and NA transporters in rat
      brain: an autoradiographic study.
AB  - Tricyclic antidepressants and serotonin (5-HT) uptake inhibitors rapidly block
      uptake sites, or transporters; however, their therapeutic effects are only seen
      after 2-3 weeks of treatment. Thus, direct blockade of 5-HT and noradrenaline
      (NA) transporters cannot account entirely for their clinical efficacy, and other
      long-term changes may be involved. Adult Sprague-Dawley rats were treated for 21
      days with daily injections of either desipramine, trimipramine, fluoxetine, or
      venlafaxine; a fifth group that was used as a control, received daily saline
      injections. Identified cortical areas, hippocampal divisions and nuclei raphe
      dorsalis, raphe medialis and locus coeruleus were examined by quantitative
      autoradiography using either [3H]citalopram to label 5-HT transporters, or
      [3H]nisoxetine for NA uptake sites. Increases in [3H]nisoxetine binding were
      found in the cingulate, frontal, parietal, agranular insular, entorhinal and
      perirhinal cortices as well as in the hippocampal divisions CA1, CA3, dentate
      gyrus and subiculum, and in nucleus raphe dorsalis of trimipramine-treated
      animals compared to the control rats. Also, densities of NA transporters
      decreased in temporal cortex, CA2 and nucleus raphe dorsalis in fluoxetine
      treated rats as compared to the controls. Also, there was a decrease in NA
      transporters in the locus coeruleus of the desipramine-treated animals as
      compared to the densities measured in the control group. Chronic treatment with
      desipramine or trimipramine, which do not directly inhibit 5-HT uptake, compared
      to fluoxetine and venlafaxine, lead to increases in 5-HT transporter densities in
      cingulate, agranular insular and perirhinal cortices. The present study shows
      differential region-specific effects of antidepressants on 5-HT and NA
      transporters, leading to distinct consequences in forebrain areas.

PMID- 10913688
TI  - Regional distribution and pharmacological characteristics of [3H]N-acetyl
      aspartyl-glutamate (NAAG) binding sites in rat brain.
AB  - Autoradiographical studies revealed that 10 nM [3H]N-acetyl-aspartyl-glutamate
      (NAAG) labelled grey matter structures, particularly in the hippocamus, cerebral
      neocortex, striatum, septal nuclei and the cerebellar cortex. The binding was
      inhibited by (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)-glycine (DCG IV), an
      agonist at group II metabotropic glutamate receptors (mGluR II). (RS)-alpha
      Methyl-4-tetrazolylphenylglycine (MTPG), (RS)-alpha-cyclopropyl-4
      phosphonoglycine (CPPG) and (RS)-alpha-methylserine-O-phosphate monophenyl ester
      (MSOPPE), all antagonists at mGluR II and mGluR III, also inhibited [3H]NAAG
      binding. Other inhibitors were (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate
      (ACPD), a broad-spectrum mGluR agonist with preference for groups I and II and
      the mGluR I agonists/mGluR II antagonists (S)-3-carboxy-4-hydroxyphenylglycine
      (3,4-CHPG) and (S)-4-carboxy-3-hydroxyphenylglycine (4,3-CHPG). Neither the mGluR
      I specific agonist (S)-dihydroxyphenylglycine nor any of the ionotropic glutamate
      receptor ligands such as kainate, AMPA and MK-801 had strong effects (except for
      the competitive NMDA antagonist CGS 19755, which produced 20-40% inhibition at
      100 microM) suggesting that, at low nM concentrations, [3H]NAAG binds
      predominantly to metabotropic glutamate receptors, particularly those of the
      mGluR II type. Several studies have indicated that NAAG can interact with mGluR
      II and the present study supports this notion by demonstrating that sites capable
      of binding NAAG at low concentrations and displaying pharmacological
      characteristics of mGluR II exist in the central nervous tissue. Furthermore, the
      results show that autoradiography of [3H]NAAG binding can be used to quantify the
      distribution of such sites in distinct brain regions and study their pharmacology
      at the same time.

PMID- 10913690
TI  - Modulation of choline acetyltransferase synthesis by okadaic acid, a phosphatase
      inhibitor, and KN-62, a CaM kinase inhibitor, in NS-20Y neuroblastoma.
AB  - Choline-O-acetyltransferase (ChAT) is the enzyme which catalyses the biosynthesis
      of the neurotransmitter acetylcholine in cholinergic neurons. Here we show that
      in mouse cholinergic NS-20Y neuroblastoma cells cultured in the presence of
      either okadaic acid (serine/threonine phosphatases 1 and 2A inhibitor) or KN-62
      (CaM kinase inhibitor) ChAT activity and mRNA either increased or decreased as a
      function of the drug concentration, respectively. After 24 h exposure, okadaic
      acid exerted a dramatic effect on cell morphology; cells became round and had no
      more neurites. On the contrary, KN-62 induced a slight morphological
      differentiation of the cells. The present results suggest that phosphatases 1 and
      2A and CaM kinase could mediate regulation of ChAT gene expression.

PMID- 10913691
TI  - Representational difference analysis of Neisseria meningitidis identifies
      sequences that are specific for the hyper-virulent lineage III clone.
AB  - Neisseria meningitidis may cause meningitis and septicemia. Since the early
      1980s, an increased incidence of meningococcal disease has been caused by the
      lineage III clone in many countries in Europe and in New Zealand. We hypothesized
      that lineage III meningococci have specific DNA sequences, providing an
      opportunity to facilitate epidemiological studies by detecting lineage III
      isolates rapidly. Applying representational difference analysis on one lineage
      III tester strain and two non-lineage III driver strains, we identified three
      lineage III-specific sequences, probably part of a single locus encoding a
      restriction modification system. A PCR based on one of these sequences identified
      lineage III meningococcal isolates with a sensitivity of 100% and a specificity
      of 93%, which is superior to the serological identification of lineage III
      isolates.

PMID- 10913692
TI  - The iron-responsive regulator Fur of Campylobacter jejuni is expressed from two
      separate promoters.
AB  - A lacZ-based reporter gene system was used to identify the promoter of the
      Campylobacter jejuni iron-responsive gene regulator Fur. In other Gram-negative
      bacteria, the fur promoter is usually located directly upstream of the fur gene
      and is often autoregulated in response to iron. In this study we demonstrate that
      expression of the C. jejuni fur gene is controlled from two promoters located in
      front of the first and second open reading frames upstream of fur. Neither of
      these promoters was iron-regulated, and the presence of both promoters in front
      of fur gives higher expression of the lacZ reporter than with either promoter
      alone. Expression from two distal promoters might be a mechanism for regulating
      the level of the C. jejuni Fur protein in response to unknown stimuli.

PMID- 10913693
TI  - Estimation of fungal biomass and transcript levels in Tilia platyphyllos-Tuber
      borchii ectomycorrhizae.
AB  - Very little information is available to date about the complex truffle life cycle
      which involves the succession of three developmental phases. In order to gain
      more knowledge about ectomycorrhizal formation and fruit body development an
      ectomycorrhizal model system was used to study fungal biomass and plant and
      fungal transcript levels. They were evaluated in ectomycorrhizal development
      using the ergosterol assay and the internal transcribed spacer-5.8S ribosomal DNA
      from Tilia platyphyllos and Tuber borchii as molecular probes respectively. The
      results obtained from different approaches revealed a decrease in fungal biomass,
      transcript and protein levels during ectomycorrhizal development.

PMID- 10913694
TI  - The cyl genes of Streptococcus agalactiae are involved in the production of
      pigment.
AB  - The cyl genes of Streptococcus agalactiae are required for the production of
      hemolysin. Based on the observation that nonhemolytic S. agalactiae mutants do
      not produce pigment, a close genetic linkage between hemolysin and pigment has
      been postulated. To investigate this genetic linkage and to identify genes
      involved in the production of the S. agalactiae pigment, we screened mutant
      libraries for nonpigmented clones. Four distinct mutants were isolated with a
      nonpigmented and nonhemolytic phenotype. The mutations had occurred either in
      known cyl genes or in two open reading frames located immediately downstream.
      These novel genes are cotranscribed with the cyl gene cluster and were designated
      cylF and cylI. Our data indicate that identical genes participate in the
      production of S. agalactiae hemolysin and pigment.

PMID- 10913695
TI  - Phospholipase A secreted by Legionella pneumophila destroys alveolar surfactant
      phospholipids.
AB  - Destruction of alveolar surfactant phospholipids by bacterial phospholipases is
      suggested to be a major virulence factor involved in bacterial pneumonia. Since
      Legionella pneumophila secretes phospholipase A, we analyzed phospholipid
      degradation in natural bovine surfactant by L. pneumophila. Phospholipids were
      reduced in amount after incubation with bacteria or culture supernatant of L.
      pneumophila serogroup 6. Free fatty acids and lysophosphatidylcholine were
      formed, the latter is known to be highly cytotoxic. Surface tension of surfactant
      as determined by pulsating bubble surfactometer increased significantly compared
      to the control. Phospholipase A activity seems to be a powerful agent of
      legionellae in causing lung disease.

PMID- 10913696
TI  - The Mycobacterium bovis homologous protein of the Mycobacterium tuberculosis
      serine/threonine protein kinase Mbk (PknD) is truncated.
AB  - We previously identified a 70-kDa serine/threonine protein kinase (MbK or PknD)
      from Mycobacterium tuberculosis Erdman containing a transmembrane domain and
      bearing a 270-amino acid N-terminal kinase domain. With the use of a polyclonal
      serum, Mbk has now been identified by Western blotting in protein extracts from
      M. tuberculosis and confirmed to be localised in the envelope. An identical mbk
      gene has been found by sequencing different M. tuberculosis and M. africanum
      strains. Surprisingly, in two virulent M. bovis strains and four different
      strains of M. bovis BCG, an additional adenine after position 829 of the open
      reading frame was found that produces a frame shift resulting in a predicted
      truncated, presumably free cytoplasmic protein, encoding only the N-terminal 30
      kDa Mbk kinase domain. This sequence polymorphism has been confirmed by Western
      blot analysis of M. bovis BCG protein extracts.

PMID- 10913697
TI  - Analysis of the dormancy-inducible narK2 promoter in Mycobacterium bovis BCG.
AB  - Upon depletion of oxygen, the obligate aerobe mycobacteria switch from growth to
      a state of non-replicating persistence or dormancy. Here, we report the first
      functional analysis of a dormancy-dependent mycobacterial promoter in
      Mycobacterium bovis BCG. Promoter probing using a 'lacZ reporter detected a
      dormancy-inducible promoter activity upstream of the coding sequence for the
      putative nitrite extrusion protein NarK2. Primer extension analysis mapped a
      transcriptional start point 47 bp upstream of the narK2 start codon. Deletion
      analysis revealed that the sequence -222 to -133 bp upstream from the
      transcriptional start point was required for basal and dormancy-inducible
      reporter expression. The sequence +1 to +47 downstream of the transcriptional
      start point had a strong inhibitory effect on the level of dormancy-induced beta
      galactosidase activity. The identification of apparent activating and inhibiting
      regions suggests that the narK2 promoter is at least under dual control.

PMID- 10913698
TI  - Expression and purification of the mannose recognition domain of the FimH
      adhesin.
AB  - Type 1 fimbriae have been shown to be specifically required for Escherichia coli
      colonisation and pathogenesis of the urinary tract. These structural organelles
      mediate specific adhesion to alpha-D-mannosides by virtue of the FimH adhesin.
      FimH is a two-domain protein in which the N-terminal domain contains the receptor
      binding site and the C-terminal domain is required for organelle integration. To
      date, FimH has only been isolated as a complex with the system-specific chaperone
      FimC. Here we report that a functional form of the FimH receptor-binding domain
      can be readily isolated and characterised by replacing the C-terminal domain with
      a histidine tag.

PMID- 10913699
TI  - Purification and biochemical characterization of a basic superantigen
      (SPEX/SMEZ3) from Streptococcus pyogenes.
AB  - A potent basic superantigen (designated streptococcal pyrogenic exotoxin X,
      SPEX/SMEZ3) was purified to homogeneity from culture supernatants of a
      Streptococcus pyogenes scarlatina strain of type 12 (genotype speA(-), speC(-))
      and characterized. Sequence alignments revealed SPEX to be an allele of the
      streptococcal mitogens type Z (SMEZ). The N-terminal amino acid sequence of SPEX
      was found with LEVDNNSLLR to be identical to the recently described acidic
      superantigen SMEZ. Although SPEX/SMEZ genes were present in all of the
      streptococcal strains tested, a toxin production could only be detected in a
      small number of strains. The produced toxin concentration in the culture
      supernatants of positive strains differed between 0 and 20 ng ml(-1). The
      purified SPEX stimulated human T-lymphocytes with Vbeta8 specificity at extremely
      low concentrations (lower than 100 pg ml(-1)).

PMID- 10913700
TI  - Accumulation of an artificial cell wall-binding lipase by Bacillus subtilis wprA
      and/or sigD mutants.
AB  - A recombinant lipase, CWB-LipB, localized on the Bacillus subtilis cell surface
      and retaining lipase activity was unstable and not accumulated in a high yield.
      To improve the accumulation, we examined cell wall binding protease (wprA)-
      and/or sigma D (sigD)-deficient mutants, and also a NprE and AprA protease
      deficient mutant as host strains. The nprE aprA mutation did not lead to a
      significant increase in the CWB-LipB accumulation. The wprA mutant accumulated a
      greater amount than the wild-type only in the stationary phase, but the sigD
      mutant accumulated a greater amount in both the exponential and stationary
      phases. The double mutant exhibited great accumulation of CWB-LipB, the amount
      being 36% of the total proteins extracted from the cell surface.

PMID- 10913702
TI  - Stimulation of adhesiveness, infectivity, and competitiveness for nodulation of
      Bradyrhizobium japonicum by its pretreatment with soybean seed lectin.
AB  - Soybean seed lectin stimulates adsorption of Bradyrhizobium japonicum to its host
      roots. Pretreatment of the rhizobia with soybean seed lectin for at least 6-12 h
      previous to their interaction with the plants was required to detect the
      stimulatory effect. This activity could be observed with as few as 1000 soybean
      seed lectin molecules per bacterium, and required specific carbohydrate binding.
      Infectivity and competitiveness for nodulation were also stimulated by
      preincubation of the rhizobia either with soybean seed meal extract or soybean
      seed lectin, the extract being more effective in enhancing competitiveness.

PMID- 10913701
TI  - Characterization of an amylase produced by a Trichoderma harzianum isolate with
      antagonistic activity against Crinipellis perniciosa, the causal agent of
      witches' broom of cocoa.
AB  - An isolate of Trichoderma harzianum showing antagonistic activity against
      Crinipellis perniciosa, the causal agent of the witches' broom disease of cocoa,
      produces substantial amounts of hydrolytic enzymes. An amylase purified from
      isolate 1051 had a molecular mass of about 68.7 kDa. Maximal activity against
      soluble starch was determined at pH 4.0 and 60 degrees C. The K(m) and V(max)
      values were 3.5 mg ml(-1) and 1.67 mg min(-1) of reducing sugar. The end products
      were mostly malto-oligosaccharides. The enzyme also hydrolyzed glycogen,
      amylopectin, maltotriose, and maltotetraose, but not pullulan or cellobiose.
      Maltose was only barely hydrolyzed. The purified amylase exerted a discrete
      hydrolytic effect on the C. perniciosa cell wall in vitro as observed by scanning
      electron microscopic analysis. While Fe(3+), Al(3+), Zn(2+), and Cu(2+) were
      effective in inhibiting the purified amylase, Mn(2+) considerably enhanced the
      activity. Ca(2+), Mg(2+), and Co(2+) showed no substantial effect on enzyme
      activity.

PMID- 10913703
TI  - Development of a competitive polymerase chain reaction assay for the ruminal
      bacterium Butyrivibrio fibrisolvens OB156 and its use for tracking an OB156
      derived recombinant.
AB  - A competitive polymerase chain reaction assay targeting the 16S rDNA was
      developed for quantitating the rumen bacterium Butyrivibrio fibrisolvens OB156. A
      competitor DNA, serving as an internal control in the competitive polymerase
      chain reaction reaction, was constructed by polymerase chain reaction using a
      looped oligo longer than the normal primer. Coamplification of the target DNA
      with known amounts of the competitor DNA allowed quantitation of the target DNA
      in both pure culture and mixed culture systems, where minimum quantifiable level
      of OB156 was 1.7x10(2) and 5.6x10(4) cells, respectively. When an erythromycin
      resistant recombinant derived from OB156 was inoculated into a rumen fluid
      culture, its numbers decreased with time. The rate of decrease measured by the
      competitive polymerase chain reaction assay was much slower than the rate
      determined by culture enumeration using erythromycin selection. The competitive
      polymerase chain reaction assay also showed 48 h persistence of the recombinant
      at 10(4) ml(-1) even after disappearance of culturable recombinant, suggesting
      maintenance of the target DNA from uncultivable cells. In an in vivo tracking
      trial, the recombinant became undetectable within 72 h with either assay,
      indicating rapid hydrolysis and/or outflow of the cells from the rumen.

PMID- 10913704
TI  - Identification of a truncated, but functionally active tet(H) tetracycline
      resistance gene in Pasteurella aerogenes and Pasteurella multocida.
AB  - Molecular analysis of Pasteurella isolates of animal origin for plasmid-encoded
      tetracycline resistance genes identified a common tet(H)-carrying plasmid of 5.5
      kbp in a single isolate of Pasteurella aerogenes and six isolates of Pasteurella
      multocida. This plasmid carried a truncated Tn5706 element in which one of the IS
      elements, IS1596, was lost completely and of the other, IS1597, only a relic of
      84 bp was left. Sequencing of the resistance gene region and the flanking areas
      revealed the presence of a deletion in the 3' end of the tet(H) gene which
      shortened the tet(H) reading frame by 24 bp. The amino acid sequence of the
      respective TetH protein comprised only 392 amino acids. Despite this deletion,
      the tet(H) gene conferred high level tetracycline resistance not only to the
      original Pasteurella isolates but also to the respective Escherichia coli JM107
      and C600 transformants as confirmed by MIC determination. The deletion was
      probably the result from recombinational events. Two possible recombination sites
      involved in the deletion of tet(H) and that of IS1597 were identified.
      Macrorestriction analysis of the Pasteurella isolates carrying plasmid pPAT1
      confirmed horizontal and vertical transfer of this plasmid.

PMID- 10913705
TI  - Frame-shift mutations in NAD(P)H flavin oxidoreductase encoding gene (frxA) from
      metronidazole resistant Helicobacter pylori ATCC43504 and its involvement in
      metronidazole resistance.
AB  - Metronidazole is a critical ingredient for combination therapies of Helicobacter
      pylori infection, the major cause of peptic ulcer and gastric cancer. It has been
      recently reported that metronidazole resistance from H. pylori ATCC43504 is
      caused by the insertion of a mini-IS605 sequence and deletion of sequences in an
      oxygen insensitive NAD(P)H nitroreductase encoding gene (rdxA). We also found
      that an additional gene (frxA) encoding NAD(P)H flavin oxidoreductase in the same
      strain was truncated by frame-shift mutations. To assess whether the frxA
      truncation is also involved in metronidazole resistance, metronidazole sensitive
      H. pylori strains ATCC43629 and SS1 were transformed by the truncated frxA gene
      cloned from strain ATCC43504. All transformed cells grew on agar plates
      containing 16 microg ml(-1) of metronidazole. The involvement of the frxA gene in
      metronidazole resistance was also confirmed by insertion inactivation of frxA
      and/or rdxA genes from strain ATCC43629 and one metronidazole sensitive clinical
      isolate H. pylori 2600. In addition, the frxA gene cloned from the H. pylori 2600
      showed metronidazole nitroreductase activity in Escherichia coli and rendered
      ordinary metronidazole resistant E. coli to metronidazole sensitive cell. These
      results indicate that the frxA gene may also be involved in metronidazole
      resistance among clinical H. pylori isolates.

PMID- 10913706
TI  - Lack of a significant role for the PerR regulator in Bacillus subtilis spore
      resistance.
AB  - Bacillus subtilis cells lacking the PerR repressor which regulates transcription
      of genes encoding oxidative stress protective proteins grew at 30-50% the rate of
      wild-type cells, and perR cultures accumulated rapidly growing suppressor mutants
      lacking the catalase whose expression is regulated by PerR. However, perR spores
      which retained the perR regulated catalase were obtained on plates. These perR
      spores had levels of oxidative stress protective proteins from 7- to 50-fold
      higher than those in wild-type spores, but perR spore resistance to heat,
      hydrogen peroxide and t-butyl hydroperoxide was essentially identical to that of
      wild-type spores, indicating that elevated levels of proteins that protect
      growing cells from oxidizing agents play no role in dormant spore resistance to
      these compounds. However, germinated perR spores were much more resistant to
      alkyl hydroperoxides than were wild-type spores.

PMID- 10913708
TI  - Corrigendum to "Identification of a putative LPS-associated cation exporter from
      rhizobium leguminosarum bv. Viciae"

PMID- 10913707
TI  - Characterization of glk, a gene coding for glucose kinase of Corynebacterium
      glutamicum.
AB  - The glk gene from Corynebacterium glutamicum was isolated by complementation
      using Escherichia coli ZSC113 (ptsG ptsM glk). We sequenced a total of 3072 bp
      containing the 969-bp open reading frame encoding glucose kinase (Glk). The glk
      gene has a deduced molecular mass of 34.2 kDa and contains a typical ATP binding
      site. Comparison with protein sequences revealed homologies to Glk from
      Streptomyces coelicolor (43%) and Bacillus megaterium (35%). The glk gene in C.
      glutamicum was inactivated on the chromosome via single crossover homologous
      recombination and the resulting glk mutant was characterized. Interestingly, the
      C. glutamicum glk mutant showed poor growth on rich medium such as LB medium or
      brain heart infusion medium in the presence or absence of glucose, fructose,
      maltose or sucrose as the sole carbon source. Growth yield was reduced
      significantly when maltose was used as the sole carbon source using minimal
      medium. The growth defect of glk mutant on rich medium was complemented by a
      plasmid-encoded glk gene. A chromosomal glk-lacZ fusion was constructed and used
      to monitor glk expression, and it was found that glk was expressed constitutively
      under all tested conditions with different carbon sources.

PMID- 10913709
TI  - Functional magnetic resonance imaging with intermolecular multiple-quantum
      coherences.
AB  - For the first time, we demonstrate here functional magnetic resonance imaging
      (fMRI) using intermolecular multiple-quantum coherences (iMQCs). iMQCs are
      normally not observed in liquid-state NMR because dipolar interactions between
      spins average to zero. If the magnetic isotropy of the sample is broken through
      the use of magnetic field gradients, dipolar couplings can reappear, and hence
      iMQCs can be observed. Conventional (BOLD) fMRI measures susceptibility
      variations averaged over each voxel. In the experiment performed here, the
      sensitivity of iMQCs to frequency variations over mesoscopic and well-defined
      distances is exploited. We show that iMQC contrast is qualitatively and
      quantitatively different from BOLD contrast in a visual stimulation task. While
      the number of activated pixels is smaller in iMQC contrast, the intensity change
      in some pixels exceeds that of BOLD contrast severalfold.

PMID- 10913710
TI  - Event-related fMRI of auditory and visual oddball tasks.
AB  - Functional magnetic resonance imaging (fMRI) was used to investigate the spatial
      distribution of cortical activation in frontal and parietal lobes during auditory
      and visual oddball tasks in 10 healthy subjects. The purpose of the study was to
      compare activation within auditory and visual modalities and identify common
      patterns of activation across these modalities. Each subject was scanned eight
      times, four times each for the auditory and visual conditions. The tasks
      consisted of a series of trials presented every 1500 ms of which 4-6% were target
      trials. Subjects kept a silent count of the number of targets detected during
      each scan. The data were analyzed by correlating the fMRI signal response of each
      pixel to a reference hemodynamic response function that modeled expected
      responses to each target stimulus. The auditory and visual targets produced
      target-related activation in frontal and parietal cortices with high spatial
      overlap particularly in the middle frontal gyrus and in the anterior cingulate.
      Similar convergence zones were detected in parietal cortex. Temporal differences
      were detected in the onset of the activation in frontal and parietal areas with
      an earlier onset in parietal areas than in the middle frontal areas. Based on
      consistent findings with previous event-related oddball tasks, the high degree of
      spatial overlap in frontal and parietal areas appears to be due to modality
      independent or amodal processes related to procedural aspects of the tasks that
      may involve memory updating and non-specific response organization.

PMID- 10913711
TI  - Quantification of cerebral blood flow by bolus tracking and artery spin tagging
      methods.
AB  - This study deals with perfusion quantification in healthy volunteers using two
      types of dynamic magnetic resonance imaging (MRI) methods. Absolute cerebral
      blood flow (CBF) measurements were performed in 11 subjects by applying both
      bolus tracking of exogenous contrast agent and non-invasive arterial spin
      labeling MRI techniques. Both methods produced CBF images with good tissue
      contrast and CBF values are in good agreement with literature data. The
      correlation between cerebral blood volume (CBV) and CBF is also discussed.

PMID- 10913712
TI  - Disappearance of tumor contrast on contrast-enhanced FLAIR imaging of cerebral
      gliomas.
AB  - Contrast-enhanced fluid-attentuated inversion recovery (FLAIR) magnetic resonance
      (MR) imaging has shown to be a valuable diagnostic modality in the assessment of
      cerebral gliomas. In this study we report of a potential pitfall regarding the
      delineation of enhancing tumor parts on contrast enhanced FLAIR imaging. In a
      limited number of patients, the administration of gadolinium obscures the area of
      contrast enhancement on contrast enhanced FLAIR images. Therefore the delineation
      of the macroscopic tumor parts, which are of great importance for the treatment
      planning is substantially worsened.

PMID- 10913713
TI  - MR imaging of the ischiopubic synchondrosis.
AB  - The ischiopubic synchondrosis (IPS) is a temporary joint, occurring in childhood
      prior to fusion of the ischial and pubic bones. On conventional radiographs this
      tumor-like appearance is a well known normal anatomic variant, however, there are
      no reports in the literature of the appearance of IPS on MRI. Therefore the
      purpose of this study was to evaluate typical magnetic resonance features of the
      IPS. All pelvic MRIs from 1/1992 to 4/1998 of children ranging in age from 4 to
      16 years, who were scanned for reasons other than bone disorders, were
      retrospectively investigated. Twenty-eight children were included and the
      morphologic appearance of IPS on MRI was evaluated. Seventeen (61%) of these 28
      children had the following findings of IPS on MRI. Listed in order of frequency
      we found signal alteration of the ischiopubic fusion zone [hyperintense on T(2)
      with fat-saturation (89%) or STIR (74%), hypointense on T(1) (71%)], fibrous
      "bridging" (68%) [hypointense band on all sequences in perpendicular orientation
      to the axis of the inferior pubic ramus], fusiform swelling (68%), signal
      alteration of the adjacent soft tissue (57%) and irregular margins (56%). In 10
      children contrast enhanced scans were available for evaluation, showing contrast
      enhancement of the bone marrow in 83.3% and of the adjacent soft tissue in 66.7%.
      Fusiform swelling of the ischiopubic fusion zone, signal alteration and contrast
      enhancement of both the bone marrow and the adjacent soft-tissue are
      characteristic features of the IPS on MRI, which may be due to mechanical stress
      at this temporary joint. These features are nonspecific and may resemble tumor,
      infection or trauma. Fibrous "bridging" was the only finding on MRI, which has
      not been described for any other entity and thus, it seems to be a characteristic
      MRI-feature.

PMID- 10913714
TI  - Detection of areas with viable remnant tumor in postchemotherapy patients with
      Ewing's sarcoma by dynamic contrast-enhanced MRI using pharmacokinetic modeling.
AB  - An approach is presented for monitoring the effects of neoadjuvant chemotherapy
      in patients with Ewing's sarcoma using dynamic contrast-enhanced perfusion
      magnetic resonance (MR) images. For that purpose, we modify the three-compartment
      pharmacokinetic permeability model introduced by Tofts et al. (Magn Reson Med
      1991;17:357-67) to a two-compartment model. Perfusion MR images acquired using an
      intravenous injection with Gadolinium (Gd-DTPA) are analyzed with this two
      compartment pharmacokinetic model as well as the with an extended pharmacokinetic
      model that includes the (local) arrival time t(0) of the tracer as an endogenous
      (estimated) parameter. For each MR section, a wash-in parameter associated with
      each voxel is estimated twice by fitting each of the two pharmacokinetic models
      to the dynamic MR signal. A comparison of the two wash-in parametric images
      (global versus local arrival time) with matched histologic macroslices
      demonstrates a good correspondence between areas with viable remnant tumor and a
      high wash-in rate. This can be explained by the high number and permeability of
      the (leaking) capillaries in viable tumor tissue. The novel pharmacokinetic model
      based on a local arrival time of tracer results in the best fit of the wash-in
      rate, the most important factor discerning viable from nonviable tumor
      components. However, parameter estimates obtained with this model are also more
      sensitive to noise in the MR signal. The novel pharmacokinetic model resulted in
      a sensitivity between 0.22 and 0.60 and a specificity between 0.61 and 1. The
      model based on a global arrival time gave sensitivities between 0.33 and 0.77 and
      specificities between 0.58 and 0.99. Both statistics are computed as the fraction
      of correctly labeled voxels (viable or nonviable tumor) within a specified ROI,
      which delineates the tumor. We conclude that the added value of estimating the
      local arrival time of tracer first manifests itself for moderate noise levels in
      the MR signal. The novel pharmacokinetic model should moreover be preferred when
      pharmacokinetic modeling is applied on the average signal intensity within a ROI,
      where noise has less effect on the fitted parameters.

PMID- 10913715
TI  - Hepatic alveolar echinococcosis: MRI findings.
AB  - The purpose of this study was to describe the magnetic resonance imaging (MRI)
      appearance of hepatic alveolar echinococcosis (HAE) on T(1)-weighted, T(2)
      weighted and postgadolinium images. A total of 13 lesions were demonstrated in 13
      patients. All patients underwent MR examination at 1 T imager. MR examinations
      included precontrast T(1)-weighted breathing averaged spin echo (SE), breath-hold
      spoiled gradient echo, T(2)-weighted TSE sequences with and without fat
      suppression, and T(1)-weighted breath-hold spoiled gradient echo (SGE) sequence
      following i.v. after gadolinium administration. All lesions were confirmed with
      histopathology. HAE hepatic lesions revealed geographic patterns of variable
      signal intensities on noncontrast T(1)- and T(2)-weighted images. Slightly
      hyperintense, iso- and hypointense signal on T(1)-weighted images corresponded to
      calcified regions, which appeared hypo-isointense signal on T(2)-weighted images.
      Necrotic areas were hypointense signal on T(1)-weighted and hyperintense signal
      on T(2)-weighted images. On postgadolinium images, lesions did not reveal
      enhancement. Dilatation of intrahepatic bile ducts distal to HAE abscesses were
      observed in five patients and portal vein invasion or compression was observed in
      four patients, lobar atrophy of the liver was coexistent finding in cases with
      portal vein compression. The MRI appearance of HAE abscesses included large
      irregularly marginated masses with heterogenous signal on T(1)- and T(2)-weighted
      images and lack of enhancement with gadolinium.

PMID- 10913717
TI  - Three-dimensional myocardial strain analysis based on short- and long-axis
      magnetic resonance tagged images using a 1D displacement field.
AB  - A robust algorithm to estimate three-dimensional strain in the left-ventricular
      heart wall, based on magnetic resonance (MR) grid-tagging in two sets of
      orthogonal image planes, is presented. Starting-point of this study was to
      minimize global interpolation and smoothing. Only the longitudinal displacement
      was interpolated between long-axis images. Homogeneous strain analysis was
      performed using small tetrahedrons. The method was tested using a stack of short
      axis images and three long-axis images in six healthy volunteers. In addition,
      the method was subjected to an analytical test case, in which the effect of noise
      in tag point position on the observed strains was explored for normally
      distributed noise (0.5 mm RMS). In volunteers, the error in the longitudinal
      displacement due to interpolation between the long-axis image planes was -0.10 +/
      0. 48 mm (mean +/- SD). The resulting error in the longitudinal strain
      epsilon(l) was -0.003 +/- 0.02. The analytical test case was used to quantify the
      effects of three sources of errors on the observed strain. The SD of the
      difference between homogeneous strain and true strain was 0.06 for epsilon(r.)
      The error due to the 3-D reconstruction was 0.004 for epsilon(r.) The error in
      epsilon(r) resulting from simulated noise in the tag point position was 0.10.
      Equivalent results were obtained for all other strain parameters; thus, the error
      resulting from noise in the tag point position dominates the error introduced by
      approximations in the method. Because the proposed method uses a minimum of
      global interpolation and smoothing, it offers the prospect to detect small
      regions of aberrant contraction.

PMID- 10913716
TI  - A prospective assessment of breath-hold fast spin echo and inversion recovery
      fast spin echo techniques for detection and characterization of focal hepatic
      lesions.
AB  - The purpose of this study was to prospectively assess two breath-hold T(2)
      weighted fast spin-echo sequences and two breath-hold inversion recovery fast
      spin-echo sequences to determine their relative ability to detect and
      characterize focal hepatic lesions. Fourteen patients with a total of nineteen
      proven focal hepatic lesions were imaged with two breath-hold T(2)-weighted (T2W)
      fast spin echo sequences (HASTE TE = 66 and HASTE TE = 120), two breath-hold
      inversion recovery fast spin echo sequences (IRFSE TE = 64 and IRFSE TE = 95),
      and a nonbreath-hold T(2)-weighted fast-spin echo sequence (FSE TE = 96-120).
      Contrast-to-noise ratios (CNRs) were measured for all proven lesions on all
      sequences. Both IRFSE sequences and the HASTE sequence with TE = 66 showed an
      improvement in lesion-liver and liver-spleen CNRs compared to the nonbreath-hold
      T2W sequence. The mean difference in CNR between benign and malignant lesions was
      largest for the HASTE TE = 120 sequence. These preliminary results suggest that a
      breath-hold IRFSE sequence (TE = 64 or 95) has an equal ability to detect focal
      hepatic lesions as a nonbreath-hold T2W FSE sequence (TE = 96-120). The HASTE TE
      = 120 showed the greatest ability to discriminate between benign and malignant
      lesions.

PMID- 10913718
TI  - A model system for perfusion quantification using FAIR.
AB  - Flow-sensitive experiments (FAIR) have been performed on a tube-flow phantom in
      order to validate quantitative perfusion measurements on humans. A straight
      forward correspondence between perfusion and bulk-flow is found. It is shown that
      the flow phantom model only holds when the slice profiles of the involved RF
      pulses are taken into account. A small flow-independent off-set may be present in
      the data. The off-set is explained by the model. Based on the correspondence
      between the phantom and the in vivo models, it is shown that the lowest flow
      values that could be measured in the phantom correspond to perfusion values lower
      than the cortical perfusion in the brain. Thus, the experimental accuracy and the
      computational methods for quantitative perfusion measurements in vivo can be
      validated by a tube-flow phantom.

PMID- 10913719
TI  - Fluoroscopically triggered contrast-enhanced 3D MR DSA and 3D time-of-flight
      turbo MRA of the carotid arteries: first clinical experiences in correlation with
      ultrasound, x-ray angiography, and endarterectomy findings.
AB  - The aim of this article was to obtain initial experiences with fluoroscopically
      triggered contrast-enhanced (CE) 3D MR DSA with elliptical centric k-space order
      and 3D time-of-flight (TOF) turbo MRA of the carotid arteries. In this
      prospective study we examined 16 consecutive patients with suspicion of
      atherosclerotic disease involving the carotid arteries. Ultrasound was available
      in all, x-ray angiography in 12, surgical correlation in 9, and intraoperative x
      ray angiography in 4 patients. All examinations were done on a 1.5 T unit
      applying: transverse plain 3D TOF turbo MRA and coronal CE MRA with fluoroscopic
      triggering. Combining head and neck array coils allowed the visualization of
      supraaortic arteries from the aortic arch to the circle of Willis. MRA results
      (maximum intensity projections) were compared with x-ray angiography, ultrasound,
      and inspection of endarterectomy specimens. Volume rendering was performed in
      selected cases additionally. Agreement between CE MRA, 3D TOF turbo MRA and x-ray
      angiography regarding stenoses of the internal and external carotid artery was
      very good. CE MRA was able to detect correctly intracranial stenoses, but
      delineation of the aortic arch and proximal common carotid arteries was sometimes
      reduced. Volume rendering was suited for visualization of MRA images providing a
      realistic three-dimensional impression. In conclusion, high-resolution
      fluoroscopically triggered CE MRA as non-invasive technique is another important
      step on the way to replace invasive x-ray angiography for the evaluation of
      atherosclerotic carotid artery disease. High resolution 3D TOF turbo MRA might be
      a helpful adjunct to increase the diagnostic reliability for the carotid
      bifurcation.

PMID- 10913720
TI  - Quantitative assessment of rat kidney function by measuring the clearance of the
      contrast agent Gd(DOTA) using dynamic MRI.
AB  - Magnetic resonance imaging (MRI) has been applied to assess kidney function in
      normal rats by monitoring the passage of the extracellular contrast agent GdDOTA.
      High-resolution images have been obtained using either the rapid acquisition with
      relaxation enhancement (RARE) or the snapshot pulse sequence. The latter was
      superior in anatomic definition due to the shorter echo delays used. The GdDOTA
      induced signal enhancements in the various renal structures were theoretically
      modeled and the results of the regression analysis then used to estimate local
      tissue concentrations in renal cortex, inner medulla and outer medulla/pelvis.
      The concentration-time curves in vena cava and renal cortex were similar and
      distinctly different from the ones in medulla and pelvis. This is reflected in
      the time-to-peak (TTP) values, which were TTP (blood) = 0.18 +/- 0.03 < TTP
      (cortex) = 0.26 +/- 0.05 < TTP (outer medulla) = 0.62 +/- 0.03 < TTP (inner
      medulla/pelvis) = 0.92 +/- 0.16 min. The initial tracer uptake rates depended
      linearly on the dose of GdDOTA administered, the value of the uptake rate in the
      cortex being significantly higher than those in the outer and inner medulla,
      which were identical within error limits. The initial medullar tracer uptake
      followed a first-order kinetics. The rate constant k(cl) =
      (dc[medulla]/dt)/c[cortex] = 3.4 +/- 0.5 min(-1) for the transition from cortex
      (predominantly blood signal) to medulla (predominantly urine) was considered a
      measure for the renal clearance. Intravenous administration of furosemide at
      doses 2.5, 5, and 10 mg/kg led to a dose-dependent decrease of k(cl). This
      reflects the inhibitory effect of the diuretic furosemide on medullary water
      resorption and thus the dilution of the GdDOTA in urine.

PMID- 10913721
TI  - Quantitative MRS: comparison of time domain and time domain frequency domain
      methods using a novel test procedure.
AB  - For quantitative analysis of in vivo MR spectra, a state-of-the-art time domain
      method was compared with a recently reported time domain frequency domain method
      which uses wavelets for background characterization. The comparison was made on
      the basis of results for simulated test problems that were constructed by
      combining measured and simulated MRS data at different signal-to-noise ratios in
      order to simultaneously reflect real world difficulties, in particular the
      overlapping background problem, and to allow for quantitative judgment of a
      method's accuracy. Incorporating prior knowledge was also considered. The results
      obtained give insight into the accuracy of the methods when applied to measured
      MRS data. Due to the improved background characterization, the time domain
      frequency domain method outperformed the time domain method in some of the test
      cases. Both methods were also applied to serial brain MR spectra of a healthy
      volunteer on 10 occasions.

PMID- 10913723
TI  - Finite size disc gradient coil set for open vertical field magnets.
AB  - A new analytical approach is used in the design of disc-like gradient coils
      suitable for magnet geometries with main field direction perpendicular to the
      surface of the disc. An inverse procedure is used to optimize the coil's
      characteristics, subject to the restrictions imposed by the desired field
      behavior over a certain set of constraint points inside a predetermined imaging
      volume. Excellent agreement between the expected values of the gradient magnetic
      field and the numerical values generated by applying the Biot-Savart law to a
      discrete current pattern of the perspective disc coil was found. A Finite Element
      Analysis package was used to predict the fringe gradient field levels for a non
      shielded axial disc coil and for a self-shielded transverse disc coil in the
      vicinity of the magnet poles. The numerical results indicate that for the self
      shielded design the gradient fringe field is 1000 times smaller than the
      corresponding fringe field for the non-shielded disc case. Also no significant
      spatial dependence was noticed for the shielded coil's fringe field.

PMID- 10913722
TI  - In vivo (31)P-MRS assessment of cytosolic [Mg(2+)] in the human skeletal muscle
      in different metabolic conditions.
AB  - Cytosolic free [Mg(2+)] can be assessed in vivo by (31)P-MRS from the chemical
      shift of beta-ATP. The reliability of in vivo measurements depends on the
      availability of appropriate in vitro calibration curves obtained by using
      solutions that mimic the in vivo cytosolic conditions as far as possible. We
      build a semi-empiric equation that correlates the chemical shift of beta-ATP to
      free [Mg(2+)] taking into account the amount of Mg(2+) bound to all other ligands
      in solution. Our experiments resulted in a reliable ten-parameters equation
      directly usable to assess the cytosolic free [Mg(2+)] of human skeletal muscle at
      rest, during work and recovery. Our experiments also resulted in a new equation
      that allows the assessment of cytosolic pH from the chemical shift of Pi taking
      into account the measured free [Mg(2+)]. To perform simultaneous calculation of
      free [Mg(2+)] and pH in the skeletal muscle in different metabolic conditions we
      developed a specific software package available on Internet
      (http://www.unibo.it/bioclin) together with another program based on the equation
      previously obtained to calculate cytosolic free [Mg(2+)] in the human brain. The
      reliability and effectiveness of our equations and software were tested on the
      calf muscles of healthy volunteers at rest, during work and recovery.

PMID- 10913724
TI  - A constrained Gauss-Seidel method for correction of point spread function effect
      in MR spectroscopic imaging.
AB  - Magnetic resonance spectroscopic imaging is limited by a low signal-to-noise
      ratio, so a compromise between spatial resolution and examination time is needed
      in clinical application. The reconstruction of truncated signal introduces a
      Point Spread Function that considerably affects the spatial resolution. In order
      to reduce spatial contamination, three methods, applied after Fourier transform
      image reconstruction, based on deconvolution or iterative techniques are tested
      to decrease Point Spread Function contamination. A Gauss-Seidel (GS) algorithm is
      used for iterative techniques with and without a non-negative constraint (GS+).
      Convergence and noise dependence studies of the GS algorithm have been done. The
      linear property of contamination was validated on a point sample phantom. A
      significant decrease of contamination without broadening the spatial resolution
      was obtained with GS+ method compared to a conventional apodization. This post
      processing method can provide a contrast enhancement of clinical spectroscopic
      images without changes in acquisition time.

PMID- 10913725
TI  - Sleep alterations in juvenile neuronal ceroid-lipofuscinosis.
AB  - In juvenile neuronal ceroid-lipofuscinosis (JNCL), sleep disorders are common.
      The purpose of this study was to investigate the sleep structure of 28 patients
      with JNCL compared with healthy controls subjects and to clarify the
      pathophysiology underlying the sleep disturbances in these patients. Each of 28
      patients with JNCL (age range = 6-27 years), with or without sleep complaints,
      underwent one night of polysomnography. Electroencephalographic, electro
      oculographic, electromyographic, and electrocardiographic findings were recorded.
      Sleep was scored and analyzed visually. The sleep parameters of the patients were
      compared with those of healthy control subjects. In most of the patients, the
      total sleep time, sleep efficiency, and percentages of rapid eye movement (REM)
      and non-REM (NREM) stage 2 sleep were significantly decreased, and the
      percentages of NREM stage 1 and slow-wave sleep and the number of nocturnal
      awakenings significantly increased. The percentage of NREM stage 1 and the number
      of awakenings increased with age and clinical stage. Paroxysmal epileptiform
      activity during light sleep (NREM stages 1-2) and high-amplitude delta-wave
      activity with intermingled sharp waves during slow-wave sleep were characteristic
      of the recordings. The present study revealed that in patients with JNCL, sleep
      is consistently altered.

PMID- 10913726
TI  - Growth hormone deficiency in children with neurofibromatosis type 1 without
      suprasellar lesions.
AB  - Risk factors for shortness of stature in children with neurofibromatosis type 1
      (NF-1) include suprasellar lesions, which can lead to growth hormone deficiency
      (GHD), skeletal deformities, nutritional insufficiency, and methylphenidate use.
      At our Neurofibromatosis Clinic, we have observed short children growing poorly
      without these risk factors. This study investigated whether GHD occurs in
      children with NF-1 in the absence of suprasellar lesions. Of 251 children with NF
      1, 112 were at or below the 25th percentile for height (68 were at or below the
      10th). Of these, 51 children, 5-16 years of age were short, growing poorly, and
      without medical or radiologic findings to explain the poor growth. In 19 of 51,
      we evaluated GH secretion; 15 of 19 had GHD (peak GH level less than 5 ng/mL in
      most cases). These findings suggest that GHD may be relatively common in short
      children with NF-1 without suprasellar abnormalities, suggesting an association
      with NF-1 independent of organic, pituitary damage. Larger cohorts of NF-1
      children should be evaluated to clarify whether NF-1 represents a novel etiology
      of GHD. Also, a careful assessment of GH secretion in children with NF-1 who are
      growing poorly in the absence of another clinical explanation is warranted.

PMID- 10913727
TI  - Weight gain associated with valproate in childhood.
AB  - Weight gain is a common side effect of valproate treatment. Several mechanisms
      have been suggested for its pathophysiology; of these, impairment of beta
      oxidation of fatty acids and increased insulin secretion have been supported by
      clinical studies. To investigate whether changes in carnitine and insulin levels
      had a role in the weight gain occurring with valproate treatment in children, 20
      patients with epilepsy were randomly assigned to receive either carnitine or
      placebo supplementation in addition to valproate. After a follow-up period of 3
      months, weight gain was observed in both groups. The mean insulin concentration
      and insulin/glucose ratios increased. Weight gain did not correlate with
      carnitine levels. These results suggest that weight gain during valproate
      treatment is not related to a decrease in carnitine levels. However, an increase
      in insulin levels together with a decrease in glucose levels may cause weight
      gain, possibly by stimulating appetite.

PMID- 10913728
TI  - Cerebral oxygenation state in childhood moyamoya disease: a near-infrared
      spectroscopy study.
AB  - Near-infrared spectroscopy was used to measure the relative concentration changes
      of oxygenated hemoglobin (HbO(2)), deoxygenated hemoglobin (HbR), and total
      hemoglobin (t-Hb) before, during, and after hyperventilation in eight patients
      with childhood moyamoya disease who underwent surgery. The patients were divided
      into the following two groups: those with and those without re-build-up
      phenomenon on electroencephalography. All patients except one exhibited decreased
      concentrations of HbO(2) and t-Hb during hyperventilation and decreased
      concentrations of HbO(2) and increased concentrations of HbR after
      hyperventilation. The difference between the hemoglobin concentration during and
      after hyperventilation was significantly greater in the group with the re-build
      up phenomenon than the group without it (P <0.03, Mann-Whitney U test). The
      patients with the re-build-up phenomenon had lower HbO(2) and higher HbR
      concentrations after hyperventilation. The concentrations of HbO(2) and HbR
      reflect an alteration in the oxygenated blood supply and/or oxygen use. Thus, it
      is strongly suggested that regional cerebral hypoxia and metabolic oxygen
      disturbances play an important role in the occurrence of the re-build-up
      phenomenon. Near-infrared spectroscopy is a useful noninvasive method to evaluate
      the efficacy of surgical treatment in childhood moyamoya disease.

PMID- 10913729
TI  - Spectrum of epileptic syndromes with electrical status epilepticus during sleep
      in children.
AB  - There has been much debate about the nosologic forms of electrical status
      epilepticus during sleep (ESES) that can occur in a number of syndromes. The
      pathogenesis of ESES is unknown, and the natural course is variable. It is
      debatable whether these age-specific epileptic syndromes belong to the same
      spectrum of disorders with different severity but a common denominator of sleep
      related hypersynchronization of generalized paroxysmal epileptic discharges. This
      report describes 18 children with medically refractory seizures, gradual
      deterioration in language skills, fine-motor incoordination, behavioral changes,
      psychologic and intellectual regression of different degrees, and the ESES
      phenomenon. Most exhibited clinical and electroencephalographic responses to
      intravenous or oral benzodiazepines, especially if initiated within the first 2
      years of seizure onset. Seizure remission was nearly complete with cessation of
      seizures and marked improvement in language and fine-motor skills, behavior, and
      intellectual function in those with an idiopathic etiology. Therapeutic trials
      with benzodiazepines should be given to all children with the ESES phenomenon.
      Sleep electroencephalographic monitoring is recommended in all young children
      with epilepsy and language or psychologic deterioration so that the brain
      dysfunction can be reversed at a critical and vulnerable period of early life.

PMID- 10913730
TI  - Infection: a stimulus for tic disorders.
AB  - The object of this study was to investigate the potential association of
      infections, especially group A hemolytic streptococcal infection, with the abrupt
      onset/exacerbation of tics or obsessive-compulsive behaviors. A structured
      clinical interview was used to evaluate 80 consecutive children, 5-17 years of
      age, with a diagnosis of tic disorder. Forty-two patients (53%) described a
      sudden, explosive onset or worsening of tic symptoms; 15 of these 42 had their
      exacerbation historically associated with an infection, nine of the 15
      specifically with a streptococcal infection. Comparisons between those nine
      individuals and the remainder of the study population are presented. The results
      of this study reveal that descriptions of an abrupt tic onset or exacerbation are
      not uncommon in children with tic disorders; approximately 11% of children with
      tic disorders described abrupt changes of tic behavior within a 6-week period
      after a streptococcal infection.

PMID- 10913731
TI  - Prognosis of seizures occurring in the first year.
AB  - To determine whether predictors of neurodevelopmental outcome and the course of
      epilepsy can be identified in infants 1-12 months of age presenting with their
      first afebrile seizure, we collected demographic data, seizure details (type,
      frequency, duration, etiology, and treatment), developmental status, neurologic
      findings at presentation and follow-up, and electroencephalographic (EEG),
      neuroimaging, metabolic, hematologic, and chemistry test results by chart review,
      parental interview, and neurologic examination in 40/41 subjects (98%) presenting
      to our institution between January 1994 and December 1998. The mean duration of
      follow-up from onset of seizures was 29 months (S.D. = 17; range = 1-64).
      Predictors of developmental and neurologic abnormalities at follow-up included
      developmental delay and abnormal neurologic examination at presentation,
      infantile spasms, lack of response to antiepileptic drugs (AEDs), valproate use,
      and abnormal EEG or neuroimaging results. Predictors against seizure control and
      epilepsy remission and for the development of problematic seizures at follow-up
      included valproate use and lack of response to AEDs. Poor neurodevelopmental
      outcome of children with new-onset afebrile seizures in the first 1-12 months of
      age can be accurately predicted at diagnosis with the aid of EEG and neuroimaging
      studies. The course of epilepsy is more difficult to predict, but failure to
      respond to the first AED is worrisome.

PMID- 10913732
TI  - Prevalence of celiac antibodies in children with neurologic disorders.
AB  - Neurologic complications are a recognized but unusual manifestation of celiac
      disease (CD) in adults and children. The use of antigliadin and antiendomysial
      antibodies in screening has revealed the frequency of CD among symptom-free
      individuals to be high. Recently, a high frequency (57%) of antigliadin
      antibodies was demonstrated in adult patients with neurologic dysfunctions of
      unknown cause. We investigated the yield of screening for CD in children with
      common neurologic disorders. One hundred sixty-seven children, 1-16 years of age,
      were included in the study: 41 with migraine headaches, 39 with attention-deficit
      disorder with or without hyperactivity, 36 with epileptic disorders, and 51 with
      hypotonia and motor abnormalities. Positive IgG antigliadin antibodies were
      evident in 22 children (13%) in the study group compared with three children (9%)
      in the control group. However, in all children, negative IgA and endomysial
      antibodies were observed; thus duodenal biopsies were not performed. Contrary to
      studies performed in adults, these results did not demonstrate any relationship
      between common neurologic disorders without a specific diagnosis during childhood
      and CD. Thus screening for CD does not need to be routinely included in the
      diagnostic evaluation of children with these disorders.

PMID- 10913733
TI  - Neck-tongue syndrome.
AB  - Two patients with neck-tongue syndrome, a rare disorder of the upper cervical
      nerves that results in paroxysmal neck pain and paresthesia of the tongue, are
      described. Signs are the result of compression of the C2 root by disorders
      affecting the first two cervical vertebrae. Conservative management is effective
      in most cases if no masses are in the involved area. The disorder has been
      observed rarely in children. Clinical onset occurred at 6 and 11 years of age,
      respectively, in the reported patients.

PMID- 10913734
TI  - Sturge-Weber syndrome without facial nevus.
AB  - An 11-month-old patient with Sturge-Weber syndrome with the absence of facial
      angioma and normal mental development is presented. Noncontrast computed
      tomography revealed left parieto-occipital atrophy with heavy gyriform
      calcifications. Axial T(2)-weighed magnetic resonance imaging confirmed the
      presence of low-signal areas corresponding to the gyral calcifications evident on
      computed tomography. Contrast-enhanced T(1)-weighted axial and coronal images
      exhibited high signals in the left parieto-occipital cortical and subcortical
      areas, representing angiomatous malformations. The clinical appearance and
      pathologic features of the reported patient were compared with those of similar
      patients described in published reports.

PMID- 10913735
TI  - Mitochondrial cytopathy combined with Fanconi's syndrome.
AB  - Severe muscle weakness in Fanconi's syndrome is rarely the result of
      mitochondrial cytopathy. We describe a rare case of a 9-year-old male with early
      onset of Fanconi's syndrome. He developed severe proximal muscle weakness
      exacerbated by hypokalemia and hypophosphatemia in childhood. The muscle biopsy
      revealed increased accumulation of abnormal mitochondria and fat droplets in
      histochemical stains and electron microscopy. Mitochondrial cytopathy cannot be
      excluded in Fanconi's syndrome with late onset of muscular impairment. Long-term
      follow-up of his clinical course is suggested to understand the natural history
      of this unusual case.

PMID- 10913736
TI  - Congenital cytomegalovirus infection: a retrospective diagnosis in a child with
      pachygyria.
AB  - A 2-year, 6-month-old child with pachygyria demonstrated on magnetic resonance
      imaging at 12 months of age, psychomotor delay, and deafness who was diagnosed
      with congenital cytomegalovirus infection by the demonstration of cytomegalovirus
      DNA in blood from the stored neonatal filter paper is reported. The use of this
      technique provides an opportunity for the retrospective viral diagnosis in
      children with neurodevelopmental impairments and abnormalities, such as migration
      disturbances, in the brain.

PMID- 10913737
TI  - Blue rubber bleb nevus syndrome with central nervous system involvement.
AB  - An 11-month-old female patient presented with focal seizures. She was born at
      term with multiple scattered tiny protuberances and dark purple soft compressible
      nevi over her entire body. She had clumsiness and decreased muscle power in her
      left extremities. Magnetic resonance imaging and magnetic resonance angiography
      revealed cerebral atrophy of the right central area around the anomalous venous
      sinus and multiple small enhancing lesions throughout the brain with gadolinium
      diethylenetriamine pentaacetic acid enhancement. Despite right partial neonatal
      seizures, she had no further seizures for 3 years while receiving carbamazepine,
      and no change was observed in the number and size of the nevi. At last
      evaluation, language and psychomotor development were normal for her age.

PMID- 10913738
TI  - Mutation detection in an equivocal case of Friedreich's ataxia.
AB  - Compound heterozygosity at the Friedreich's ataxia locus accounts for
      approximately 2% of molecularly confirmed cases. Genotype-phenotype correlation
      in this subgroup of patients reveals a spectrum of clinical variability. This
      report describes the clinical and molecular findings in a 6-year-old patient with
      Friedreich's ataxia who carried a pathologic GAA expansion of approximately 1,000
      repeats on one allele and a novel initiation codon point mutation (3G-->A) on the
      other.

PMID- 10913739
TI  - Tourette's syndrome and neurofibromatosis type 1.
AB  - The case of an 11-year-old male with clinical features compatible with a
      diagnosis of Tourette's syndrome and neurofibromatosis type 1 is reported.
      Magnetic resonance imaging revealed bilateral pallidal hyperintensities, which
      may be related to the tic disorder.

PMID- 10913740
TI  - Winter birth and biological family history in adopted schizophrenics.
AB  - To investigate relationships between birth season and biological family history
      in schizophrenia, this study used a sample of schizophrenics that had the
      advantages of (a) particularly thorough diagnostic assessments of schizophrenics'
      relatives, including information from direct interviews as well as chart reviews,
      and (b) schizophrenic probands who were adopted at early age, mitigating the
      usual confounding of genetic and postnatal environmental influences of the
      family. Adopted schizophrenics with no biological family history of schizophrenia
      spectrum disorders were significantly more likely to be born in winter months
      than were either (a) their own biological relatives, including their sibs and
      half-sibs, (b) schizophrenics with a positive family history for schizophrenia
      spectrum disorders, or (c) people in the general population. Family-history
      positive schizophrenics and their schizophrenic relatives were, in turn,
      significantly less likely than their own non-schizophrenic biological relatives
      to be born in the winter; schizophrenics in these families tended to be born in
      the milder-weather seasons, particularly the spring and fall. Results suggest
      that environmental factors associated with winter birth may be etiologically
      important in schizophrenia, particularly for cases in which familial liability
      factors are weak. By contrast, a familial, probably genetic, liability factor may
      be especially important in schizophrenics born in mild weather.

PMID- 10913741
TI  - Seasonality of schizophrenia and stillbirths in The Netherlands.
AB  - Studies from Denmark and the USA have reported a strong correlation between the
      seasonal pattern for stillbirths and the seasonal birth pattern for people who
      develop schizophrenia. It has been suggested that the correlation could be caused
      by a common seasonal factor (e. g. intra-uterine infections during the third
      trimester of pregnancy), which produces death in some fetuses and nonfatal brain
      changes in others, changes that are manifested in later life as schizophrenia.
      The aims of our study were (i) to assess the seasonal patterns for stillbirths
      and for pre-schizophrenic births in The Netherlands and (ii) to examine their
      relationship. The Dutch psychiatric registry provided data on all Dutch-born
      subjects who had been hospitalized at least once with a diagnosis of
      schizophrenia in the period 1970-1994. We selected data on patients born in the
      period 1926-1970 (n=29891). The government provided monthly numbers of live
      births and stillbirths in the latter period. Seasonality of birth was examined
      using Poisson regression analysis. The risk of an admission for schizophrenia was
      highest for people born in the months of May and June and lowest for those born
      in August and September. When the risk for subjects born in June was compared
      with the risk for subjects born in September, the Relative Risk was 1.14 [95%
      confidence interval (CI): 1.07 to 1.22]. The seasonal pattern of stillbirths was
      different, in that it showed a peak in the month of January. The low, however, as
      in schizophrenia, occurred in the months of August and September. The two
      seasonal patterns were found to be weakly correlated: Spearman's rank correlation
      coefficient rho=0.41 (95% CI: -0.22 to 0.80). This was the largest European study
      on birth seasonality in schizophrenia. The hypothesis that a common factor is
      responsible for a seasonal excess of stillbirths and for a seasonal birth excess
      of people who develop schizophrenia was not supported. The possibility remains,
      however, that a common factor explains seasonal (birth rate) deficits in these
      disorders.

PMID- 10913742
TI  - Schizophrenia and birth order in Pakistan.
AB  - The paper describes a two stage study. In Stage I the birth orders of 453 adult
      patients with different diagnoses, seen in the routine work of a general hospital
      psychiatry department, were compared. Patients with schizophrenia had
      significantly higher average birth positions than patients with other diagnoses,
      even after controlling for sibship size.In Stage II, the birth positions of 64
      patients with schizophrenia (DSMIIIR) were subjected to a goodness-of-fit chi
      square test. Over-representation of eldest siblings was highly significant for
      both sexes. When patients aged 30 and above were analysed separately, there was
      still a significant excess of first-born. These findings are in contrast to birth
      order studies of schizophrenia in western populations. In the authors' opinion,
      they can not be accounted for by the biases to which birth order studies are
      prone. They indicate a need for further community-based studies.

PMID- 10913743
TI  - Behavioral neurodevelopment abnormalities and schizophrenic disorder: a
      retrospective evaluation with the Childhood Behavior Checklist (CBCL).
AB  - This study is a retrospective report of childhood and adolescence neurobehavioral
      assessment in patients with schizophrenia and their healthy siblings using the
      Childhood Behavior Checklist (CBCL). The CBCL ratings were obtained from
      retrospective maternal reports, for five age periods (birth to 3years, 4-7years,
      8-11years, 12-15years and 16-18years) in a sample of 32 patients with
      schizophrenia. The patients showed a variety of childhood and adolescence
      behavioral problems when compared with their siblings, and the various types of
      problems differed in the developmental course of the disease. Cluster analysis
      was conducted on the childhood premorbid behavior ratings for the schizophrenic
      patients, and two subgroups emerged: a cluster with an initially low level of
      behavioral abnormalities (B.A. ) that increased over the years, and a cluster
      with a high level of B.A. that remain relatively stable until early adulthood.
      The latter group showed more severe current negative symptoms.

PMID- 10913744
TI  - Childhood schizotypy and positive symptoms in schizophrenic patients predict
      schizotypy in relatives.
AB  - BACKGROUND: Schizotypy is one phenotypic expression of the familial-genetic
      liability to schizophrenia, but its precise relationship to frank psychotic
      symptoms remains unclear. We, therefore, set out to examine the relationships
      between (a) premorbid personality in schizophrenic patients, (b) the
      psychopathology they showed, and (c) schizotypal traits in their relatives.
      METHOD: Ninety consecutively admitted schizophrenic patients were interviewed
      with the Present State Examination (PSE). Their mothers were interviewed
      concerning their childhood personality and social adjustment, and 121 of their
      well relatives were evaluated with three different schizotypal scales. Factor
      analyses were carried out on (a) the nine main psychotic symptoms from the
      patients' PSE interview, and on (b) the schizotypal features derived from the
      scales completed by the first-degree relatives. Correlation coefficients were
      calculated between premorbid personality traits, and factor scores in probands
      and in relatives. RESULTS: No relationship was found between childhood schizoid
      schizotypal personality traits and any particular dimension of psychopathology in
      patients. The positive syndrome in patients was correlated with higher scores for
      relatives on the three schizotypy scales, but did not predict any specific
      pattern of schizotypy in the relatives. Premorbid schizoid-schizotypal traits
      were also correlated with schizotypy in the relatives. CONCLUSIONS: Schizotypy in
      relatives has a familial relationship with schizoid-schizotypal traits in the
      childhood, and with positive symptoms during the illness, of schizophrenic
      patients.

PMID- 10913745
TI  - Premorbid personality disorders in schizophrenia.
AB  - Premorbid personality disorders (PD) were studied retrospectively in 40
      schizophrenic patients by interviewing the parents and patients who were reliable
      with the SCID-II. 85% of the patients had premorbid PDs. The most frequent
      premorbid PDs were: avoidant PD (32. 5%), schizoid PD (27.5%), paranoid PD (20%),
      dependent PD (20%) and schizotypal PD (12.5%). In most of the patients, two or
      more PDs could be diagnosed simultaneously (47.5%), comorbilidity of the
      premorbid PDs in schizophrenia being the most common one. The most frequent
      combination was avoidant-schizoid-schizotypal PD.

PMID- 10913746
TI  - Impact of duration of symptoms prior to first hospitalization on acute outcome in
      998 schizophrenic patients.
AB  - The hypothesis that a longer duration of symptoms prior to first hospitalization
      is associated with a poorer treatment response was prospectively investigated in
      998 first-hospitalized schizophrenic patients. Results indicate that most
      indicators of outcome were worse when the duration of symptoms was long. This was
      also true when age, gender, as well as the acuteness of illness were controlled
      for in the analyses.

PMID- 10913747
TI  - The stanley foundation brain collection and neuropathology consortium.
AB  - The Stanley Foundation brain collection is an attempt to supplement existing
      brain collections for the purpose of promoting research on schizophrenia and
      bipolar disorder. Specimens are collected with the permission of the families in
      a standardized manner, with half of each specimen being frozen and half fixed in
      formalin. The Neuropathology Consortium is a subset of 60 specimens from the
      collection, well-matched groups of 15 each with diagnoses of schizophrenia,
      bipolar disorder, major depressive disorder without psychotic features, and
      normal controls. More than 75000 sections and blocks from the Consortium have
      been sent to over 50 research groups worldwide to carry out a wide variety of
      assessments. These data will be integrated to provide a more complete picture of
      the neuropathology of these disorders.

PMID- 10913748
TI  - Transport of drugs from the nasal cavity to the central nervous system.

PMID- 10913749
TI  - Water-activated, pH-controlled patch in transdermal administration of timolol. I.
      Preclinical tests.
AB  - Previously, transdermal patches with internal pH-controlled release were
      described. The aim of this study was to test the suitability of the patch design
      in transdermal delivery and, further, to select such transdermal patch
      formulations to a clinical study with timolol. In vitro release of timolol from
      the patches was determined as well as timolol permeation across the human cadaver
      skin. The effect of the skin on drug release were evaluated in vitro. In vitro
      data and pharmacokinetic parameters from the literature were used to construct a
      pharmacokinetic model for the prediction of in vivo performance of the devices.
      With water-activated, pH-controlled silicone reservoir devices, both the rate of
      drug release and the duration of constant release were controlled. The rate of
      timolol release was decreased when the devices were placed on human cadaver skin,
      and thus, the skin partly controls the rate and extent of timolol delivery to the
      systemic circulation in vivo. On the basis of in vitro data and kinetic
      simulations, devices of 10-cm(2) volume releasing timolol in vitro at the rates
      of 119 and 10 microgh(-1)cm(-2) were selected for human tests.

PMID- 10913750
TI  - Water-activated, pH-controlled patch in transdermal administration of timolol.
      II. Drug absorption and skin irritation.
AB  - The feasibility of the water-activated, pH-controlled silicone reservoir devices
      for transdermal administration was investigated using timolol maleate as a model
      drug. Timolol patches were applied to the arm of 12 volunteers for 81 h, two
      patches per subject. Timolol absorption from patches was compared to that from a
      peroral timolol tablet formulation (Blocanol((R)) 10 mg). Furthermore, in vivo
      plasma levels of timolol were compared with those predicted by kinetic
      simulations. Skin irritation induced by timolol patches was assessed by visual
      scoring and color reflectance measurements. With water-activated, pH-controlled
      patches both steady-state concentrations of timolol in plasma and its duration
      could be controlled. However, a considerable, inter-individual variability in the
      transdermal absorption of timolol was observed. This is due to the high
      fractional skin control in timolol delivery. Timolol patches were well tolerated
      by subjects. Skin irritation induced by the combination of timolol with long-term
      occlusion was mild, and after removal of the patches, skin changes were
      practically reversed in 24 h. Simulation model was useful in prediction of
      timolol levels in plasma after transdermal administration.

PMID- 10913751
TI  - Formulation of sustained release aqueous Zn-hirudin suspensions.
AB  - Sustained release formulations for recombinant hirudin (rHir), an anticoagulant
      thrombin-specific inhibitor, were developed. Zn-rHir suspensions were formed by
      precipitation with zinc salts at neutral pH. Characterization of protein
      precipitation was by UV analysis, capillary electrophoresis (CE), zinc analysis,
      light and electron microscopy, and particle size analysis. The precipitation of
      aqueous rHir solution with ZnCl(2) solution at neutral pH resulted in Zn-rHir
      suspensions. Optimum yields of pelletized Zn-rHir were obtained between pH 7.0
      and 7.4. For complete precipitation ( approximately 100%) a molar ratio of zinc
      to rHir of >28 was necessary. As shown by electron microscopy, the smallest
      resolvable unit of Zn-rHir suspensions was 20 nm. Agglomerates of up to 200
      microm were observed by light microscopy. Zinc salt-induced precipitation
      phenomena were also investigated using ZnBr(2), ZnI(2), Zn(NO(3))(2) and ZnSO(4)
      instead of ZnCl(2). ZnSO(4) showed the lowest precipitation efficiency. All other
      salts behaved similar to ZnCl(2). Upon storage the pelletized protein content of
      the ZnCl(2) based precipitates was stable ( approximately 95% rHir after 1 year
      at room temperature), whereas the pelletized protein content of ZnSO(4) based
      precipitates dropped sharply after precipitation (2% remaining after 13 days at
      room temperature). This indicates a transition of the ZnSO(4) based precipitates
      to hexagonal basic zinc sulfate plates and free rHir. The driving force is the
      lower aqueous solubility of basic zinc sulfate as compared to the higher
      solubility of basic zinc chloride.

PMID- 10913752
TI  - Stability and in vitro metabolism of dipeptide model prodrugs with affinity for
      the oligopeptide transporter.
AB  - One approach to increase drug stability and to facilitate oral absorption of low
      bioavailability drugs may be to design oligopeptide ester prodrugs which are
      stable in the gastrointestinal tract, are transported via the oligopeptide
      transporter, and finally release the parent drug molecule into the blood
      circulation and/or by its site of action. In these kinds of prodrugs the ester
      linkage may be broken by pH dependent and/or enzyme catalyzed hydrolysis. The
      objective of the present study was to investigate the degradation mechanism and
      rate of the model compounds Glu(OBzl)-Sar, D-Glu(OBzl)-Ala and Asp(OBzl)-Sar in
      aqueous solution and in relevant biological media and to compare these results
      with those of our previous study of D-Asp(OBzl)-Ala. Furthermore, the resulting
      aqueous stability and in vitro metabolism data are related to our previous
      affinity data to evaluate if Glu-Sar, D-Glu-Ala, and Asp-Sar have potential as
      pro-moieties in these kinds of prodrugs. The degradation rates follow first-order
      kinetics, show maximun stability at pH 4-5 with maximum half-lives for Asp(OBzl)
      Sar, Glu(OBzl)-Sar, and D-Glu(OBzl)-Ala of 115 h, 30 days and 152 days,
      respectively. The stability was dependent on buffer concentration, temperature,
      pH, and ionic strength. In biological media such as 80% human plasma, human
      gastric juice and intestinal fluid, and 10% rat jejunal homogenate at 37 degrees
      C, the half-lives were greater than 1 h except for the hydrolysis of Glu(OBzl)
      Sar in 10% rat jejunal homogenate, where the half-life was approximately 16 min.
      All the stabilized dipeptides may have potential as drug carriers targeting
      hPepT1.

PMID- 10913753
TI  - Ultrasonication of pyrogenic microorganisms improves the detection of pyrogens in
      the Mono Mac 6 assay.
AB  - The monocytic cell line Mono Mac 6 is sensitive to pyrogens. When exposed to
      pyrogens secretion of interleukin-6 is induced. However, some eukaryotic
      pyrogenic microorganisms are not detectable. The aim of this study is to
      introduce a pretreatment of samples to expand the detection range of the assay.
      The interleukin-6 inducing capacity of a broad spectrum of UV-killed and
      ultrasonicated microorganisms is examined in Mono Mac 6 cells. The interleukin-6
      secretion is determined in a sandwich immunoassay (DELFIA). The Mono Mac 6 assay
      is able to detect UV-killed Bacillus subtilis, Staphylococcus aureus and
      Salmonella typhimurium, but neither Candida albicans nor Aspergillus niger. After
      ultrasonication of the microorganisms it is possible to detect C. albicans and A.
      niger. The interleukin-6 inducing ability of the examined microorganisms is in no
      case reduced after ultrasonic treatment. However, ultrasonication of S. aureus
      results in a 100-fold increase in the interleukin-6 response. Even after
      ultrasonication Streptococcus faecalis can not be detected. Ultrasonication is an
      easy and simple method for expanding the detection range in the Mono Mac 6 assay.

PMID- 10913754
TI  - Evaluation of Gottingen minipig skin for transdermal in vitro permeation studies.
AB  - The optimal skin type for in vitro permeability studies depends on the purpose of
      the specific transdermal study. In a number of cases, it may be advantageous to
      use animal skin as an alternative to human skin although they have different
      characteristics. Recently, Gottingen minipigs have been reported as good models
      in toxicological and pharmacokinetic studies of drug substances. In this paper,
      the potential use of skin from the Gottingen minipig is evaluated by studying
      three model drug substances (nicotine, salicylic acid and testosterone) through
      skin from humans, domestic pigs and three ages of the Gottingen minipig. An
      analysis of variance and a Student's t-test showed that both the skin from the
      Gottingen minipig and the domestic pig possessed transdermal permeabilities,
      which correlated with human skin and exhibited a lower intra- and intervariation.
      Furthermore, it was shown that permeability and variation of fluxes through skin
      from Gottingen minipigs were dependent on the age of the minipig and of the drug
      substance. It is concluded that the Gottingen minipig, like the domestic pig, is
      a good skin model for in vitro permeation through human skin.

PMID- 10913755
TI  - Protease inhibitors. Part 12. Synthesis of potent matrix metalloproteinase and
      bacterial collagenase inhibitors incorporating sulfonylated N-4-nitrobenzyl-beta
      alanine hydroxamate moieties.
AB  - N-4-Nitrobenzyl-beta-alanine was reacted with alkyl/arylsulfonyl halides,
      followed by conversion of the COOH to the CONHOH group. Structurally related
      compounds were obtained by reaction of N-4-nitrobenzyl-beta-alanine with aryl
      isocyanates, arylsulfonyl isocyanates or benzoyl isothiocyanate, followed by
      similar conversion of the COOH into the CONHOH moiety. Another subseries of
      derivatives was prepared from sulfanilyl- or metanilyl-4-nitrobenzyl-beta-alanine
      by reaction with arylsulfonyl isocyanates, followed by the introduction of the
      hydroxamate moiety. The new compounds were assayed as inhibitors of four matrix
      metalloproteinases (MMPs), MMP-1, MMP-2, MMP-8 and MMP-9, and of the Clostridium
      histolyticum collagenase (ChC). Some of the prepared hydroxamate derivatives
      proved to be very effective collagenase/gelatinase inhibitors, depending on the
      substitution pattern at the sulfonamido moiety. Substitutions leading to the best
      inhibitors of MMP-1, a short-pocket enzyme, were those involving
      pentafluorophenylsulfonyl or 3-trifluoromethyl-phenylsulfonyl at P(1') (K(I) of 3
      5 nM). For MMP-2, MMP-8 and MMP-9 (deep-pocket enzymes), the best inhibitors were
      those containing perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties,
      such as pentafluorophenylsulfonyl, 3- and 4-protected-aminophenylsulfonyl-, 3-
      and 4-carboxy-phenylsulfonyl-, arylsulfonylureido- or arylsulfonylureido
      sulfanilyl-/metanilyl moieties at P(1'). Bulkier groups in this position, such as
      1- and 2-naphthyl-, substituted-naphthyl or quinoline-8-yl- moieties, among
      others, led to less effective MMP/ChC inhibitors. The best ChC inhibitors were
      again those containing pentafluorophenylsulfonyl, 3- and 4-protected
      aminophenylsulfonyl P(1') groups. This study demonstrates that the 4-nitrobenzyl
      moiety, investigated here for the first time, is an efficient P(2') anchoring
      moiety, whereas the beta-alanyl scaffold can successfully replace the alpha-amino
      acyl one, for obtaining potent MMP/ChC inhibitors.

PMID- 10913756
TI  - X-ray crystallographic characterization of nilvadipine monohydrate and its phase
      transition behavior.
AB  - Crystals of nilvadipine monohydrate were obtained from aqueous acetonitrile
      solution and characterized by powder and single crystal X-ray crystallography and
      thermal analysis. Water molecules of crystallization exist in nilvadipine
      monohydrate crystals in a molar ratio of 1:1 (drug-to-water) and were fixed by
      three hydrogen bonds with two carbonyl groups of the methyl and isopropyl esters,
      respectively, and one imino group of neighboring nilvadipine molecules. The
      conformation of the methyl and isopropyl esters in the monohydrate crystal was
      the reversal of that in the anhydrate crystal due to the presence of hydrogen
      bonds with water in the former crystal. The monohydrate crystal was slowly
      converted to the dehydrate at low humidity, and the latter rapidly converted to
      the former at high humidity. Powder X-ray diffraction studies indicated that the
      dehydrate retains the original structure of the monohydrate, i.e., a layer
      structure stacked on the ac plane perpendicular to the b-axis The solubility of
      the monohydrate in water was lower than that of the dehydrate and anhydrate
      forms, although the initial dissolution rate of the monohydrate was faster than
      that of the anhydrate. The present results indicated that the conformation of 1,
      4-dihydropyridine-type calcium channel antagonists such as nilvadipine is easily
      changed by hydrogen bonds with water molecules of crystallization, and the water
      molecules are mobile through the void spaces formed between the layers in
      crystals.

PMID- 10913757
TI  - Towards improving control of zoonoses in West Africa.

PMID- 10913758
TI  - Communicable disease surveillance with limited resources: the scope to link human
      and veterinary programmes.
AB  - Zoonoses are an important cause of human disease in much of Africa, but
      limitations in current diagnosis and surveillance strategies restrict the
      effectiveness of control and prevention programmes. Outbreaks of disease, ranging
      from Ebola virus infection to Rift Valley Fever, that have occurred recently in
      Africa have demonstrated the need for improved disease surveillance and
      monitoring. Strategies are suggested for co-ordinating human and animal disease
      surveillance programmes, at the district and regional level, to make more
      effective use of limited resources.

PMID- 10913760
TI  - Detection and management of zoonotic diseases at the Kumasi slaughterhouse in
      Ghana.
AB  - Slaughterhouse surveys are important in the detection and management of zoonotic
      diseases. Routine reports from the Kumasi slaughterhouse, in the Ashanti region
      of Ghana, include cases of zoonotic diseases. Due to its location and size,
      Kumasi is the major cattle market and an important transit point for cattle trade
      from places within and outside Ghana. This present study was designed to examine
      slaughterhouse reports and to explore the nature of the knowledge, attitude and
      practices of butchers who operate at this slaughterhouse, in relation to
      zoonoses. The study was largely descriptive, employing qualitative methods and
      tools. Butchers were interviewed and their practices along the production line
      observed. The study indicates that zoonotic diseases are frequently detected at
      the Kumasi slaughterhouse. However the knowledge, attitudes, practices and
      beliefs of the butchers are largely inadequate for their profession in view of
      the important public health role that butchers play. The butchers have never
      received any form of training. It is recommended that the butchers receive
      training on a regular basis and that laws be formulated and implemented to
      protect the health of the butchers and the general public.

PMID- 10913759
TI  - Prevalence of tuberculosis in cattle in the Dangme-West district of Ghana, public
      health implications.
AB  - Bovine tuberculosis due to Mycobacterium bovis is a major cause of human
      gastrointestinal tuberculosis in developing countries where bovine milk is often
      not pasteurised before use. Little information is available on the prevalence of
      the disease in African cattle and its zoonotic impact. The Ghanaian Government,
      through its peri-urban dairy cattle development project, is promoting the use of
      milk and dairy products from local cows in selected districts of the country,
      including the Dangme-West district of the Greater Accra region. A survey was,
      therefore, undertaken to determine the prevalence of tuberculosis infection in
      cattle in this district and to assess the level of awareness with regard to the
      risks through milk consumption. The standard single intradermal comparative
      tuberculin test (SCITT) using purified protein derivative (PPD) of M. bovis and
      M. avium was used to detect cattle infected with M. bovis. The study established
      the prevalence of a 13.8% infection in cattle in the district although the
      prevalence was as high as 50% in some kraals. Prevalence was highest in the Ningo
      sub-district (19.0%), followed by Dodowa, the district capital (14.0%), while the
      other two sub-districts, Prampram and Osudoku had lower rates of 11.3 and 10. 8%,
      respectively. Cattle of all ages and both sexes were affected, but the prevalence
      in cows was twice as high as that in heifers or bulls. The study also established
      that there is a considerable lack of knowledge about bovine tuberculosis among
      cattle owners and herdsmen in the community and that milk is often used
      untreated, thus increasing the risk of human infection.

PMID- 10913761
TI  - The prevalence of anti-Toxoplasma gondii antibodies in Ghanaian sheep and goats.
AB  - The enzyme-linked immunosorbent assay (ELISA) was used to detect anti-Toxoplasma
      gondii antibodies in 1258 small ruminants (732 sheep and 526 goats) sampled from
      28 different locations in the three ecological zones of Ghana. The animals
      sampled had an overall seroprevalence of 30.5% (384 of the total). Sheep had a
      higher overall prevalence (33.2%) compared to the goats (26.8%). Animals sampled
      from the Coastal Savannah and the Forest zones had prevalences of 39.4% and
      39.1%, respectively, which were significantly higher (P<0.01) than the prevalence
      recorded for the drier Guinea Savannah zone (20%). Prevalence of antibodies in
      female animals (35.8%) was significantly higher (P<0.01) than that for males
      (21.1%). Significant differences were also observed between breeds and age
      groups. The ELISA was found to be both highly sensitive (92%) and specific (91%)
      when compared to the IFAT, which was used as a reference test.

PMID- 10913762
TI  - The seroprevalence of toxoplasmosis in pigs in Ghana.
AB  - A serological survey of toxoplasmosis in pigs in Ghana was carried out between
      October 1997 and April 1998 in the three ecological zones of Ghana: the Coastal
      Savannah, the Forest Belt and the Guinea Savannah. Antibody against Toxoplasma
      gondii was measured in pig serum using a microplate-ELISA which had a sensitivity
      and specificity of 90.2 and 92.3%, respectively when compared with IFAT. A
      national seroprevalence of 39% was obtained in pigs, with the ecological
      distribution being 43.9, 30.5 and 42.5% for the Coastal Savannah, the Forest Belt
      and the Guinea Savannah, respectively. The age of the animal, the breed, the
      environmental conditions and the management practices appeared to be the major
      determinants of prevalence of antibodies against T. gondii. The prevalence of
      anti-T. gondii antibodies was found to increase with age (P<0.05). Pigs from the
      two Savannah zones had a significantly higher (P<0.05) antibody prevalence than
      those sampled from the Forest belt. Antibody prevalence (46.8%) in crossbreed
      pigs was significantly higher (P<0.05) than that of the exotic Large White breed
      (38.8%).

PMID- 10913763
TI  - The seroprevalence of antibodies to toxoplasma gondii in domestic goats in
      Uganda.
AB  - Only limited epidemiological information is available on the seroprevalence of
      Toxoplasma gondii in domestic livestock in sub-Saharan Africa. In Uganda, goats
      are important to the local economy and are also popular food animals. A high
      incidence of T. gondii infection in goats would have implications both for animal
      production and for public health, but no data is available on Toxoplasma
      infection in these animals. In this study we estimated the seroprevalence of
      antibodies against T. gondii in goats located in both urban and rural
      environments and from different geographical regions within Uganda. Goat sera
      were collected using a random, two-stage clustering method. Of 784 samples
      analysed by antibody-ELISA from various districts in Uganda, 240 tested positive.
      The combined (cluster-adjusted) seroprevalence was 0.31 (31%) (95% confidence
      intervals 0.28, 0.34) indicating a substantial level of infection in these
      regions. Seroprevalence was significantly higher in goats from urban locations. A
      strong positive relationship between age and seroprevalence was demonstrated and
      a mathematical model based on continuous exposure proved generally accurate in
      predicting seroprevalence. Farm environments were identified as being suitable
      for oocyst survival and transmission, and the reported incidence of caprine
      abortion was high. The importance of toxoplasmosis to goat production in Uganda
      has yet to be determined, but the high seroprevalence detected in this study
      suggests that it may have a significant impact and that the consumption of goat
      meat may play a role in zoonotic transmission to humans.

PMID- 10913764
TI  - An assessment of the safety of street foods in the Ga district, of Ghana;
      implications for the spread of zoonoses.
AB  - Street food refers to food and beverages prepared and sold by vendors in streets
      and other public places for immediate consumption. In Ghana street foods are sold
      at small eating places popularly known as 'chop bars'. Food safety studies were
      conducted on the premises of 160 'chop bars' in the Ga District of Ghana in July
      1998. Only three (1.8%) of the proprietors met all the requirements (based on a
      five-point checklist) for basic hygiene. Twenty-four (15%) out of the 160
      proprietors had access to potable water while the other 136 (85%) proprietors
      purchased water from vendors and six used pond water. These two latter sources of
      water were of poor microbiological quality (as shown by faecal coliform values
      which ranged from 1.0x10(2)-1.9x10(5) cfu/ml). One hundred and five proprietors
      (65.6%) did not obtain their meat supply from an approved source. Factors
      influencing the purchase of meat from an approved source included the proximity
      of a chop bar to a slaughter facility, the conduct of meat inspection personnel
      and affordable user fees.

PMID- 10913765
TI  - Seroprevalence of brucellosis in cattle and humans in the Akwapim-South district
      of Ghana: public health implications.
AB  - A total of 183 cattle comprising 54 bulls, 53 milking cows, 76 heifers and 44
      calves in the Akwapim-South district of Ghana were tested for antibodies against
      Brucella abortus using the Rose Bengal plate test. The results indicated that
      cattle in the Akwapim-South district were infected with Brucella with a mean
      seroprevalence of 6. 6%. There was no difference in the seroprevalence either
      between females 11/129 (8.5%) and males 1/54 (1.9%), or among the three different
      breeds of cattle (Sanga, West African short horn (WASH) and white Fulani) in the
      study area. However, there was a significant increase in seropositivity with
      respect to age. A significant association between antibodies against Brucella and
      a history of abortions and retained placenta in cows indicated that brucellosis
      might be responsible for significant economic losses to farmers in the area.
      However, no evidence of human brucellosis was detected by antibody screening in
      selected risk groups.

PMID- 10913766
TI  - Human behavioural factors implicated in outbreaks of human anthrax in the Tamale
      municipality of northern Ghana.
AB  - The knowledge, attitude, beliefs and practices of cattle owners, herdsmen,
      butchers and meat consumers about anthrax were used to provide a better
      understanding of the major factors responsible for the frequent outbreaks of
      human anthrax in the Tamale municipality of northern Ghana. A total of 96% of the
      respondents, made up of 50 cattle owners, 50 herdsmen, 25 butchers and 125
      consumers, knew of anthrax and the clinical signs indicative of anthrax in
      cattle. However, very few knew the causative agent and many attributed the
      disease to the supernatural. Eight percent of the respondents believed that
      herbal preparations could protect against human anthrax, while 9% indicated that
      they would seek help from traditional practitioners or herbalists, if they
      suspected anthrax. A significant proportion of respondents were of the view that
      animals, which had died of unknown causes could be eaten because they served as a
      source of inexpensive meat for the community, especially if the meat was cooked
      with herbs which was commonly thought to prevent anthrax. These attitudes, taken
      together with the low income of the population studied, made the consumption of
      meat from animals, which had died of unknown causes, an attractive option. This
      increased the vulnerability to human anthrax in an area with frequent anthrax
      outbreaks in livestock. The results of this study suggest that a public education
      campaign involving both veterinary and local health personnel on the actual cause
      and prevention of anthrax could reduce outbreaks of anthrax in people.

PMID- 10913767
TI  - Prevalence and control of zoonotic diseases: collaboration between public health
      workers and veterinarians in Burkina Faso.
AB  - Zoonotic diseases constitute a public health problem throughout the world,
      particularly in the tropics, where their control is restricted by inadequate
      infrastructure and financial resources. Additionally, there is a lack of
      information on their significance and distribution. This study, conducted jointly
      by the Ministries of Health and Animal Resources, aimed to assess the prevalence
      of zoonotic diseases in Burkina Faso. The data were taken from internal reports
      of each ministry covering the period January 1-December 31 1996 for the Ministry
      of Health and for January 1-December 31 1997 for the Ministry of Animal
      Resources. Zoonotic diseases were divided into viral (rabies, yellow fever, HIV
      infection/AIDS, and measles), bacterial (tuberculosis, brucellosis, and anthrax)
      and parasitic (cysticercosis, toxoplasmosis, and leishmaniasis). For the period
      under study, the following diseases were reported by the Ministry of Health,
      tuberculosis, 1314 cases; anthrax, 145 cases; leishmania, 271 cases; rabies, 110
      cases; and measles, 46490 cases. The Ministry of Animal Resources reported 69% of
      rabies cases occurred in dogs; cysticercosis occurred in swine at a prevalence of
      0.57%; the prevalence of tuberculosis in cattle, small ruminants and pigs was 0.
      13, 0.013, and 0.029%, respectively; the prevalence of anthrax and echinococcosis
      was 0.012 and 0.007%, respectively; and finally, the prevalence of bovine
      brucellosis was 8% in the peri-urban areas. This study revealed that there was a
      lack of collaboration between the organisational structures and workers in both
      ministries involved in the control of zoonoses. Links between the two ministries
      in the field of public health need strengthening.

PMID- 10913769
TI  - Current status of some zoonoses in Togo.
AB  - In Togo, livestock represent an important part of the national and subsistence
      economies. The most prevalent zoonoses documented in Toga are brucellosis,
      tuberculosis, cysticercosis and rabies. The status of other zoonoses such as
      toxoplasmosis, giardiasis, cryptosporidiosis and salmonellosis is not known. A
      national eradication programme has been instigated to reduce the transmission of
      rabies. Good relations exist between veterinary and health personnel in the field
      but this level of interaction is absent at district and national level. This has
      resulted in information not being transferred between the two disciplines and the
      lack of a national strategy for the eradication of zoonoses in Togo.

PMID- 10913768
TI  - Zoonotic infections in Nigeria: overview from a medical perspective.
AB  - Infections of domestic and wild animals that are transmitted directly or by an
      arthropod vector to humans are a major cause of morbidity and mortality worldwide
      and particularly in Nigeria. With a population of over 100 million and the need
      for improved health care delivery, Nigerians are at considerable risk considering
      the seriousness of these infections. Zoonotic infections that are endemic in
      Nigeria include tuberculosis, trypanosomiasis, toxoplasmosis, taeniasis, rabies,
      lassa fever and yellow fever. Zoonotic food-borne infections (caused by
      Campylobacter, Salmonella and Escherichia coli O157:H7) and cryptosporidiosis are
      emerging. Sporadic cases such as strongyloidiasis, ascariasis, leptospirosis,
      scabies, pentastomiasis and African histoplasmosis have been reported. There is a
      need to determine the prevalence of tick-borne zoonoses. Prevention and control
      of zoonoses in humans is by vaccination, treatment and health education. As a
      first measure to improve control, the link between veterinary and medical
      officers, which is presently very weak, needs to be strengthened. Furthermore,
      regional multidisciplinary approaches to the control of zoonotic infections
      should be adopted in West Africa, which take into consideration the huge inter
      border traffic.

PMID- 10913770
TI  - The public health laboratory service (PHLS) and its role in the control of
      zoonotic disease.
AB  - The aetiology of zoonotic infections embraces organisms from every branch of the
      microbial world. In addition, zoonoses must be considered as a truly global
      problem, both in terms of their distribution and the measures required for their
      control. Within the UK, zoonotic disease is considered to be less frequent than
      in some less developed parts of the world. However, its contribution to overall
      morbidity and mortality within the UK population is not well established. In an
      attempt to define the impact of zoonotic infection more accurately, a multicentre
      prospective study of disease in farmers in England and Wales was initiated by the
      PHLS in 1992. The study involved the completion by participants of annual
      questionnaires dealing with their own health and the range and health of their
      livestock. Our results confirmed that some infections occur frequently in
      farmers. For example, ringworm and Q fever were associated with contact with
      cattle and orf with the handling of sheep. Some findings were unexpected; the
      incidence and prevalence of leptospirosis, for example, were far lower in the
      farmers than had been anticipated, whilst there was a higher than expected
      incidence and prevalence of hantavirus infection. The success of the project was
      largely due to the adoption of a multidisciplinary approach and the continuity of
      funding which enabled the study of the same cohort to continue for 7 years.

PMID- 10913771
TI  - Veterinary education, zoonoses and public health: a personal perspective.
AB  - Zoonotic disease poses an important threat to human public health and should
      therefore be taken seriously. A number of zoonoses also cause severe disease and
      loss of production in food producing animals. Many veterinarians are less aware
      of the importance of zoonoses than is desirable and medical clinicians who
      encounter zoonoses in human patients may either fail to recognise them or
      concentrate on treating the individual patient rather than disease control. This
      situation may be exacerbated where there is inadequate communication between
      veterinarians, the various health care professionals and public health
      organisations. Undergraduate and postgraduate training courses must promote a
      greater understanding of the importance of zoonoses and of how to investigate and
      control them. We also need to increase awareness amongst qualified veterinary
      personnel and human health care workers and to facilitate inter-disciplinary
      discussions and collaborative ventures. This paper suggests some ways to achieve
      these aims.

PMID- 10913772
TI  - Generalized averaging and noise levels in evoked responses.
AB  - A formal relationship between the mean square noise level in an evoked potential
      experiment, the number of averages and the autocorrelation function of the noise
      is derived. The generalized averaging process is recast as a filter applied to
      the noise signal. This filter is computed for a number of different types of
      evoked potential experiments in which various weighting factors and stochastic
      stimulation times are allowed. Although the variance in noise level estimates can
      be large, there is a general trend for noise reduction to occur more slowly than
      the expected 1/N when the total time over which averaging occurs is small in
      comparison to the correlation time of the noise. When the total averaging time
      exceeds the temporal extent of the autocorrelation function, the expected 1/N
      behavior is observed.

PMID- 10913773
TI  - Computer aided detection of microcalcifications in digital mammograms.
AB  - Microcalcification detection is widely used for early diagnosis of breast cancer.
      Nevertheless, mammogram visual analysis is a complex task for expert
      radiologists. In this paper, we present a new method for computer aided detection
      of microcalcifications in digital mammograms. The detection is performed on the
      wavelet transformed image. The calcifications are separated from the background
      by exploiting the evaluation of Renyi's information at the different
      decomposition levels of the wavelet transform. Experiments are performed on a
      standard and publicly available dataset and the results are evaluated with
      respect to recent achievements reported in the literature.

PMID- 10913774
TI  - Automated scoring of patient pain drawings using artificial neural networks:
      efforts toward a low back pain triage application.
AB  - The goal of this research was to examine methods of automatically scoring patient
      pain drawings. Two hundred and fifty pain drawings were selected from the files
      of an orthopaedic surgeon who specializes in the treatment of low back pain
      patients. An artificial neural network was designed to score these drawings. The
      drawings were segmented into 85 regions following dermatomal mappings and from
      these regions the percent area in pain in each was computed and used as the
      neural network input variables. With five outcome categories (scores) we obtained
      a classification sensitivity of 49%, which is approximately as well as physician
      experts and discriminant analysis achieved using a subset of the same data. We
      conclude that an artificial neural network is well suited to automatically score
      patient pain drawings.

PMID- 10913775
TI  - Protein selection, food intake, and body composition in response to the amount of
      dietary protein.
AB  - Though not universally observed, moderately low-protein diets have been found to
      increase caloric intake and body fat. It appears that animals overeat in calories
      in order to obtain more dietary protein. For animals to control protein intake,
      they must be able to distinguish between two isocaloric diets containing
      different percentages of protein and make the appropriate dietary selection on
      the basis of their previous history of protein intake. Experiment 1 examined the
      24-h diet selection (5 vs. 35% casein) of Sprague-Dawley rats that had been
      previously fed diets containing various percentages of dietary protein (5, 10,
      20, 35, or 60% casein). Animals fed 5, 10, or 20% dietary protein showed a
      preference for the higher protein selection diet. In contrast, no significant
      diet preference was found in animals pre-fed the two higher levels of dietary
      protein (35 or 60% casein). In this study, daily food intake and body fat of rats
      fed the low-protein diets (5 and 10% casein) were similar to rats fed the 20%
      casein diet. Experiment 2 examined the effects of the level of methionine
      supplementation on rats fed 10% casein. In this study, food intake and body fat
      were increased by approximately 20% in rats fed 10% casein diets, regardless of
      the level of methionine supplementation (0.3 vs. 0.15%). Together, the results
      suggest that the presence of low-protein-induced hyperphagia helps maintain body
      protein levels in the face of moderately low dietary protein and promotes an
      increase in the amount of body fat and energy.

PMID- 10913776
TI  - Hypothyroidism increases prolactin secretion and decreases the intromission
      threshold for induction of pseudopregnancy in adult female rats.
AB  - In order to understand the mechanism by which thyroid hormones alter prolactin
      (PRL) secretion, we investigated the role of tuberoinfundibular dopamine (TIDA)
      neurons and pituitary and hypothalamus vasoactive intestinal peptide (VIP) in
      thiouracil- (0. 03% in drinking water for 16 days) induced-hypothyroid adult
      female rats. The intromission threshold for induction of pseudopregnancy also was
      examined to evaluate the PRL response to coital stimulation in hypothyroid rats.
      Hypothyroidism in adult female rats did not affect TIDA neuronal activity as
      measured by tyrosine hydroxylase activity (DOPA accumulation 30 min after
      administration of m-hydroxybenzylhydrazine dihydrochloride, 100 mg/kg, i.p.) in
      the stalk-median eminence compared with that in euthyroid rats, whereas pituitary
      concentration of VIP was dramatically increased. Plasma concentration of PRL was
      higher at 1100 h of proestrus and estrus in hypothyroid rats as compared with
      that of euthyroid rats. The proportion of female rats exhibiting pseudopregnancy
      was higher in hypothyroid animals (100%) receiving seven intromissions than in
      euthyroid animals (43%). Administration of L-thyroxine in hypothyroid rats
      decreased the proportion of pseudopregnancy (40%) to the level of euthyroid
      animals. These results indicate that the increased level of pituitary VIP
      probably affects PRL secretion in a paracrine or autocrine manner and account for
      the hyperprolactinemia induced in hypothyroid female rats. No role for TIDA
      neurons in PRL elevation can be ascribed. A decrease in the intromission
      threshold for induction of pseudopregnancy might be due to increased levels of
      PRL in hypothyroid female rats.

PMID- 10913777
TI  - High doses of systemic DHEA-sulfate do not affect sleep structure and elicit
      moderate changes in non-REM sleep EEG in rats.
AB  - The hormone dehydroepiandrosterone (DHEA) and its metabolite DHEA-sulfate (DHEAS)
      occur in huge quantities in the plasma as well as in the brain of vertebrates. To
      investigate whether DHEAS modulates sleep-wake behavior, we assessed the sleep
      response to three doses (25, 50, and 100 mg/kg) of intraperitoneally administered
      DHEAS, mixed with oil, in 8 rats. DHEAS injections produced dose-dependent and
      long-lasting elevations in the plasma levels of both DHEAS and DHEA. DHEAS
      administration did not affect sleep time and architecture but exerted persistent
      effects on the electroencephalogram (EEG) within non-rapid eye movement sleep: 50
      mg/kg DHEAS significantly augmented EEG power in the frequency range of sleep
      spindles, and 100 mg/kg DHEAS depressed EEG power in the slow-wave frequency
      bands. The findings indicate that DHEAS changes the sleep EEG in a dose-dependent
      way, possibly through a modulation of GABA- and glutamate-induced currents.

PMID- 10913778
TI  - Learning of olfactory cues is not necessary for early lamb recognition by the
      mother.
AB  - Ewes identify their young through the use of different sensory modalities.
      Olfactory recognition, which mediates selective acceptance at the udder, is
      established at 4 h postpartum (pp). Visual and auditory cues are involved in
      recognition at a distance, which is evident at 12 h pp. This study investigates
      whether anosmic ewes are able (a) to develop visual and auditory recognition and
      (b) to restore selective acceptance of their lamb at the udder. Visual and
      auditory recognition was assessed in anosmic and intact ewes at 12 h and 24 h pp
      by a test of two choices: their own and an alien lamb. Selectivity at allowing
      suckling was tested by presenting successively an alien and the familiar lamb at
      4 h, 3 days, and 1 month pp. In the two-choice recognition test, at both 12 h and
      24 h pp, anosmic as well as intact ewes showed a preference for their familiar
      lamb. Although anosmic ewes showed no difference in their acceptance of alien and
      familiar lambs for suckling at 4 h and 3 days pp, they nursed the alien lamb less
      at 1 month pp and showed more rejection behaviors toward it. Thus, visual,
      auditory, or both those types of recognition can be rapidly established,
      independent of olfactory recognition. Moreover, differential behavior of anosmic
      ewes toward their own versus an alien lamb at the udder at 1 month suggests that
      vision and audition may compensate to some extent for the loss of olfaction.

PMID- 10913779
TI  - Effect of antimicrobial and anti-inflammatory medications on the sense of taste.
AB  - Elderly individuals and HIV-infected patients have a disproportionate number of
      taste complaints relative to the general population, and these taste alterations
      are correlated with the use of medications. Clinical reports of taste disorders
      have been associated with many drugs, including antimicrobial and anti
      inflammatory medications. The purpose of this study was to quantify the taste
      effects of 6 nonsteroidal anti-inflammatory drugs (NSAIDS) and 13 antimicrobial
      drugs. The six NSAIDS were: diclofenac sodium salt, fenoprofen calcium salt,
      ibuprofen, ketoprofen, nabumetone, and sulindac. The 13 antimicrobials were:
      acyclovir, ampicillin, atovaquone, dapsone, enoxacin, ethambutol, lomefloxacin
      HCl, ofloxacin, pentamidine isethionate, pyrimethamine, sulfamethoxazole,
      tetracycline HCl, and trimethoprim. These 19 medications were applied topically
      to the tongues of unmedicated young and elderly volunteers as well as unmedicated
      HIV-infected patients to measure the direct effect of the drug on taste
      receptors. Topical application of drugs to the apical tongue surface was used to
      mimic the situation in which the drug is secreted into the saliva. The main
      finding was that the taste qualities of these drugs were perceived as
      predominantly bitter, metallic, and/or sour, although several did not have a
      taste. Elderly subjects had higher thresholds than young subjects for one-third
      of the drugs that were tested. Thresholds for HIV-infected patients were
      statistically equivalent to young controls; however, HIV-infected patients rated
      the drugs as more intense at four times above the detection threshold than young
      subjects. Most of these drugs when applied directly to the tongue also modified
      the taste intensity of other tastants (e.g., NaCl, citric acid).

PMID- 10913780
TI  - Preproenkephalin mRNA levels are regulated by acute stress and estrogen
      stimulation.
AB  - Enkephalins facilitate female reproductive behavior. Within the limbic system and
      hypothalamus, estrogen induced the expression of preproenkephalin (PPE) mRNA.
      Estrogen injection caused a biphasic increase in the PPE mRNA levels within the
      ventromedial hypothalamic nucleus and posterodorsal medial amygdala. The first
      peak of PPE mRNA levels occurred within an hour, and the second 24 to 48 h after
      subcutaneous injection of estrogen. The present studies indicated that the rapid
      first peak of PPE mRNA expression was stress induced, whereas the second peak was
      estrogen induced. In the posterodorsal medial amygdala but not in the
      ventromedial hypothalamic nucleus, the antiestrogen, tamoxifen, did not inhibit
      the first peak, but blocked the second peak of PPE mRNA expression. Subcutaneous
      oil injection induced a 1-h peak of PPE mRNA levels but not a 24-h peak. Peak
      levels of plasma corticosterone were coincident with peak PPE mRNA levels.
      Adrenalectomy plus a constant, low level of corticosterone eliminated the
      injection-induced increase of corticosterone levels and the subsequent increase
      in PPE mRNA expression in the ventromedial hypothalamic nucleus and posterodorsal
      medial amygdala. The present results indicate that both stress steroids and
      estrogen positively regulate PPE mRNA levels in the ventromedial hypothalamic
      nucleus and posterodorsal medial amygdala. These results are consistent with the
      hypothesis that acute, mild stress may contribute to the activation of circuits
      that facilitate reproductive behavior in the female.

PMID- 10913781
TI  - Intraventricular insulin suppresses the acoustic startle response in rats.
AB  - We and others have previously reported that the hormone insulin alters brain
      noradrenergic function at the synaptic and molecular levels. In the present
      study, we examined the in vivo effect of insulin (administered chronically via
      osmotic minipumps at a dose of 5 mU/day into the third cerebral ventricle) on the
      acoustic startle response. Rats receiving chronic intraventricular insulin had a
      significantly reduced startle response relative to vehicle-treated controls
      (i.e., 47 +/- 21% of baseline control startle response). Because our previous
      findings suggest that on an acute basis, insulin may enhance endogenous
      noradrenergic activity by inhibiting norepinephrine reuptake, we speculate here
      that the chronic effect of insulin is similar to that of the noradrenergic
      reuptake blocker, desipramine, which has been reported to decrease baseline
      startle performance.

PMID- 10913782
TI  - Neonatal chorda tympani transection permanently disrupts fungiform taste bud and
      papilla structure in the rat.
AB  - The present report examined the morphology of fungiform papillae in adult rats
      that received bilateral chorda tympani transection at 10 days of age. Tongue
      tissue was examined using surface-structure analysis. Counts were made of
      fungiform papillae with a pore, fungiform papillae with no pore and fungiform
      papillae with a keratinized conical surface; a feature referred to as "filiform
      like. " Neonatal chorda tympani nerve transection resulted not only in a loss of
      taste buds but also in a permanent loss in numbers of fungiform papillae.
      Compared with an average of 152 fungiform papillae in sham-operated control rats,
      there was an average of only 54 fungiform papillae after neonatal chorda tympani
      transection. Nearly 80% of these fungiform papillae in neonatal chorda tympani
      transected rats were filiform-like. No filiform-like papillae were noted in sham
      operated rats. These results suggest that the chorda tympani nerve is necessary
      during an early postnatal period of development to maintain normal fungiform
      papillae morphology.

PMID- 10913783
TI  - Dihydrotestosterone and estrogen regulation of rat brain androgen-receptor
      immunoreactivity.
AB  - Androgen-receptor upregulation that occurs with androgenic-anabolic steroid (AAS)
      administration may be mediated by AAS metabolites, dihydrotestosterone (DHT), and
      estrogen. Castrated and intact male rats received 14 s.c. daily injections of AAS
      (2 mg/kg testosterone cypionate, 2 mg/kg nandrolone decanoate, and 1 mg/kg
      boldenone undecylenate in sesame oil vehicle), DHT (5 mg/kg dihydrotestosterone),
      EB (5 mg/kg estradiol benzoate), or sesame oil vehicle. Approximately 18-24 h
      after the fourteenth injection, brain tissues were removed and processed
      immunocytochemically using the PG-21 androgen-receptor antibody. As reported
      before, castration eliminated AR-ir (androgen-receptor immunoreactivity) and AAS
      upregulated AR-ir in the ventromedial hypothalamus (VMHVL), medial amygdala
      (MePV), and medial preoptic area (MPOM). When compared to AAS, DHT fully
      upregulated AR-ir in the VM VL and MPOM and partially upregulated AR-ir in the
      MePV. EB treatment partially upregulated AR-ir in the VMHVL and MePV, but not in
      the MPOM of castrated rats. Because AR-ir in the MPOM was consistently
      upregulated by DHT or AAS, and not EB, androgen-receptor availability in this
      region may be mediated specifically via androgen receptors.

PMID- 10913784
TI  - Pinealectomy does not affect the entrainment to light nor the generation of the
      circadian demand-feeding rhythms of rainbow trout.
AB  - The pineal organ and its secretory product melatonin are regarded as
      synchronizers of daily rhythms to the external light/dark (LD) cycle. In fish,
      the pineal organ acts as a direct photoreceptor, transducing light information
      into neural and humoral (melatonin) signals. In the present study, we investigate
      a possible role for the pineal organ and melatonin in the regulation of feeding
      rhythms of rainbow trout, Oncorhynchus mykiss. We used individual rainbow trout
      placed in an insulated room at constant temperature (14 degrees C). Fish were
      self-fed ad lib by means of self-feeders coupled to a computer that continuously
      recorded demand-feeding activity. Before and after pinealectomy, the fish were
      exposed to a LD cycle of 16:8 h and then constant light (LL) to test the effect
      of pinealectomy on demand-feeding rhythms. Feeding records revealed that trout
      fed exclusively during daytime (96% of feeding confined to the light phase), and
      that removal of the pineal organ did not disrupt this daily feeding profile, with
      synchronization to the LD cycle persisting. Moreover, the appearance of circadian
      feeding rhythms was not affected by pinealectomy: most of the operated fish free
      ran with an average tau longer than 24 h. Plasma melatonin rhythms persisted in
      the pinealectomized trout, but with small amplitude. These results suggest that
      the pineal may not be the site of the pacemaker that controls feeding rhythms in
      trout, although further research is required to study the involvement of other
      photoperiod-transducing systems and melatonin (of nonpineal origin) in the
      regulation and expression of circadian rhythms in this species.

PMID- 10913786
TI  - Effect of a presleep optokinetic stimulation on rapid eye movements during REM
      sleep.
AB  - Some evidence supports the view point that phasic motor events of REM sleep show
      a complementary relation with the corresponding wake motor activities: (a) an
      inverse relationship between waking saccades and REM sleep eye movements (REMs)
      has been found with respect to frequency, amplitude, and direction; (b) an
      increase of middle-ear muscle activity (MEMA) in the 2 h before sleep causes a
      complementary decrease of MEMA during REM sleep. The present study evaluated this
      relation with respect to the optokinetic (OKN) system, assessing the role of
      automatically induced eye movements in affecting direction and frequency of REMs
      during sleep. Ten subjects were recorded following standard rules in 3
      consecutive nights (one adaptation, one baseline, one experimental). In the
      experimental night subjects underwent 2 h presleep OKN stimulation at 15 degrees
      /s. The actual mean number of quick phases of nystagmus induced by the OKN
      stimulation was 12461.4 +/- 1.7 quick phases/s). No significant effect was found
      with regard to direction or frequency of REMs; the hypothesis that differences in
      REM direction and frequency could be modulated by the rank order of REM episodes
      (i.e., as a function of time elapsed from presleep stimulation) also failed to
      show any effect of a complementary relation between OKN and REMs. The results
      suggest that the complementary relation between wake and sleep eye movements is
      specific for the saccadic system, allowing us to exclude a peripheral mechanism,
      that is, an effect due to fatigue of extraocular muscles.

PMID- 10913785
TI  - The effect of ovarian steroids and photoperiod on body fat stores and uncoupling
      protein 2 in the marsupial Sminthopsis crassicaudata.
AB  - To determine the effects of photoperiod and ovarian steroids on fat stores in the
      marsupial S. crassicaudata, animals were ovariectomised (OVX) or sham operated,
      and maintained under either short-day (SD) or long-day (LD) photoperiods for 104
      days. Photoperiod had no effect on body weight in the sham animals. In the LD OVX
      animals, body weight fell and remained below baseline for about 45 days,
      whereafter it returned to baseline. In contrast, body weight of SD OVX animals
      increased over the first 45 days then returned to baseline. Tail width (a
      reflection of body fat stores) increased in both sham and OVX animals exposed to
      SD. When exposed to LD, tail width increased only in the OVX animals. There was
      no effect of either photoperiod or OVX on total cumulative energy intake. Leptin
      mRNA expression was increased in the LD OVX animals compared to the shams.
      Photoperiod had no effect on UCP2 mRNA expression in any tissue; however, OVX
      decreased UCP2 mRNA expression in muscle. These data indicate that in S.
      crassicaudata: (a) fat mass increases in response to both SD photoperiod and OVX
      and they have additive effects; (b) the effects of photoperiod on fat mass are
      mediated by both gonadal steroid dependent and independent mechanisms; (c)
      alterations in UCP2 mRNA expression may mediate the effect of OVX, but not
      photoperiod; and (d) UCP2 mRNA is differentially regulated in muscle and fat.

PMID- 10913787
TI  - A behavioral analysis of the ingestion of glucose, maltose and
      maltooligosaccharide by rats.
AB  - Glucose, maltose, and Polycose are stimuli that differ in their effectiveness in
      stimulating ingestion in the rat. To understand better how variation in glucose
      chain length affects the ingestion of these compounds, we compared the effect of
      six concentrations of glucose, maltose, and maltooligosaccharide (MOS) on the
      microstructure of the licking behavior of the rat. At the three lowest
      concentrations the order of effectiveness in stimulating ingestion was MOS >
      maltose > glucose. At the three highest concentrations, there were no differences
      among the three compounds in volume ingested. As measured by initial rate of
      licking, the orosensory stimulating effectiveness of the three compounds were
      ordered as MOS > maltose > glucose. The magnitude of the negative feedback
      signals were very similar for MOS and maltose and greater than glucose at all but
      the highest two concentrations of glucose, suggesting that glucose chain length,
      not caloric density, is responsible for the differences in the magnitude of
      negative feedback. With the three lowest concentrations, the ordering of the
      compounds in their ability to stimulate intake depended on orosensory stimulating
      ability.

PMID- 10913788
TI  - The role of 5alpha-reductase activity in sexual behaviors of the green anole
      lizard.
AB  - Both testosterone (T) and its metabolite, 5alpha-dihydrotestosterone (DHT), can
      facilitate male sexual behavior in the lizard Anolis carolinensis. The present
      study addresses the role of DHT synthesis in regulating male sexual behavior by
      inhibiting 5alpha-reductase, the enzyme that converts T into DHT. In two separate
      experiments (one replacement and one maintenance paradigm), breeding adult males
      were castrated and implanted with capsules of T, DHT, or a control capsule
      (blank, BL). The animals were then injected with the 5alpha-reductase inhibitor,
      FCE, or with steroid suspending vehicle (SSV) as a control. Both experiments
      produced similar results. Overall, T was most effective in eliciting courtship
      and copulatory behaviors above control levels. In both experiments, treatment
      with FCE attenuated the T-induced effects on courtship behavior, whereas the
      inhibition of 5alpha-reductase activity resulted in modest and inconsistent
      effects on the latency to intromission and the proportion of copulating males.
      DHT treatment did not significantly increase courtship or copulatory behaviors
      above control levels. These results suggest that (a) 5alpha-reductase activity is
      necessary but that DHT alone is not sufficient for stimulating courtship in male
      A. carolinensis; and (b) courtship behavior is more sensitive than copulatory
      behavior to the activity of the androgen metabolizing enzyme.

PMID- 10913789
TI  - Pharmacological antagonism of tyrosine kinases and MAP kinase in brainstem blocks
      taste aversion learning in mice.
AB  - Although c-Fos induction in the brainstem is a reliable correlate of taste
      aversion learning and appears necessary for the encoding of the unconditioned
      stimulus, little is known about the intracellular signaling pathways in the
      brainstem that regulate c-Fos expression during taste aversion learning. Infusion
      of the tyrosine kinase inhibitor genistein and the MAP kinase kinase (MEK)
      inhibitor PD98059 into the fourth ventricle of mice potently blocks acquisition
      of a learned taste aversion. The unconditioned stimulus LiCl produces a rapid and
      robust phosphorylation of MAP kinase, as revealed by immunohistochemistry with an
      antibody specific to the dually phosphorylated active form of MAP kinase. This
      immunoreactivity is localized to the same region of the intermediate nucleus
      tractus solitarius in which we have shown large increases in c-Fos immunoreactive
      cells, suggesting that in at least a subset of these cells, MAP kinase activation
      may lead to c-fos induction.

PMID- 10913790
TI  - Air righting: role of the NMDA receptor channel and hippocampal LTP.
AB  - Air righting results in an animal turning over when it is dropped from a height
      in an inverted position. In the rat, air righting is a complex set of movements
      that depends only on an intact labyrinth and the normal vestibular input. Visual
      modulation of air righting does not develop until adulthood; and the ability to
      estimate the time to impact requires bilateral visual cues and indicates that air
      righting is a complex set of perceptually controlled movements and learning. The
      general purpose of this study was to determine the role of the NMDA receptor-ion
      channel on air righting and hippocampal LTP. Specifically: to measure the effects
      of various doses of CPP, an NMDA receptor antagonist, and MK-801, an ion channel
      blocker, on (a) air righting and (b) hippocampal LTP induction in medial
      perforant path-granule cell synapses. The following doses were used: CPP-0, 1, 5,
      and 10 mg/kg i.p.; MK-801-0. 0, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg/kg i.p. Data
      were analyzed by appropriate ANOVAs and post hoc tests. Results were significant
      and demonstrate dose-dependent impairment of air righting and inhibition of LTP
      for both CPP and MK-801, implicating the role of the NMDA receptor and
      Na(+)/K(+)/Ca(2)+ channel in these effects. Air righting is a complex behavior
      and appears to be dependent upon NMDA mediated hippocampal LTP.

PMID- 10913792
TI  - Developmental stress disrupts habituation but spares prepulse inhibition in young
      rats.
AB  - Stress has long been recognized as a factor that contributes to the induction of
      schizophrenia and results in abnormal sensorimotor functioning and information
      processing. Patients with schizophrenia show disrupted habituation and prepulse
      inhibition of the acoustic startle response. This study examined the effects of
      maternal isolation in rats on the habituation of startle and PPI to assess the
      potential impact of developmental stress on schizophrenic symptomatology.
      Evaluation of performance in young adulthood (3-4 months) revealed a disruption
      of habituation in the isolated group; response amplitude increased over time. PPI
      was not altered. These results suggest that the disruption of habituation may
      involve acute effects of elevated stress hormones on neuronal functions. In
      contrast, disturbance of PPI may require an accrual of neuronal insult and damage
      to ultimately undermine neurologic function, possibly through impact on N-methyl
      D-aspartate-mediated transmission. An analysis of effects at middle age is
      planned to address this possibility.

PMID- 10913791
TI  - Red ginseng ameliorated place navigation deficits in young rats with hippocampal
      lesions and aged rats.
AB  - Effects of hippocampal lesions and aging on spatial learning and memory and
      ameliorating effects of red ginseng on learning deficits were investigated in the
      following two experiments: performance of young rats with selective hippocampal
      lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red
      ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham
      operated or intact young rats. Each rat in these two behavioral experiments was
      tested with the three types of spatial-learning tasks (distance movement task,
      DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a
      circular open field using intracranial self-stimulation as reward. The results in
      the DMT and RRPST tasks indicated that motivational and motor activity of young
      rats with hippocampal lesions with and without ginseng were not significantly
      different from that of sham-operated young rats in Experiment 1. However, young
      rats with hippocampal lesions displayed significant deficits in the PLT task.
      Treatment with red ginseng significantly ameliorated place-navigation deficits in
      young rats with hippocampal lesions on the PLT task. Similarly, red ginseng
      improved performance of aged rats on the PLT task in Experiment 2. The results,
      along with previous studies showing significant effects of red ginseng on the
      central nervous system, suggest that red ginseng ameliorates learning and memory
      deficits through effects on the central nervous system, partly through effects on
      the hippocampal formation.

PMID- 10913794
TI  - Fever and tachycardia in a bird (Gallus domesticus) after simple handling.
AB  - Three Gallus domesticus cocks were reared separately in a climatic chamber at 22
      degrees C, with lights on at 0600 and off at 1800 h. Food and water were
      available at all times. At noontime, one bird was handled for the purpose of
      taking cloacal, comb, and foot temperatures every 3 min for 18 min. Repeated
      handling produced a fever characterized by a mean rise in core temperature from
      41.1 +/- 0.3 degrees C to 41.6 +/- 0.3 degrees C and an initial peripheral
      vasoconstriction, as shown by a drop in skin temperatures. Maximum core
      temperature was only 39.9 +/- 0.2 degrees C when the birds received
      intraperitoneal salicylate 1 h before handling. It is concluded that handling
      causes a fever in birds. The birds were equipped with an electrocardiogram radio
      transmitter, and their heart rates were recorded at a distance. When simply
      touched by an experimenter, the birds' mean heart rate rose from 198 +/- 6 to 249
      +/- 15 beats/min. We conclude that fever and tachycardia might indicate the
      existence of emotion in birds.

PMID- 10913793
TI  - Varying responses to the rat forced-swim test under diurnal and nocturnal
      conditions.
AB  - The paradox that experiments in behavioural pharmacology employing nocturnal
      rodent species are carried out almost exclusively in the resting phase of the
      animals' circadian cycle has remained largely unexamined and unquestioned. This
      is despite the fact that all major physiological systems in the body are
      intrinsically aligned with its natural circadian rhythm. The forced-swim test
      (FST) is a rodent model that is used extensively as a screening test for
      antidepressant activity. The objectives of the present study were to examine the
      behaviour of rats in the FST under diurnal and nocturnal conditions and, in
      addition, to profile the response of neurochemical, neuroendocrine, and cellular
      indices of stress at time points up to 120 min following exposure to the FST. The
      time spent in escape-oriented activity was significantly less when animals were
      tested in the dark phase. The profile of serum corticosterone and adrenal
      ascorbic acid concentrations indicates that the animals were less stressed by the
      test situation during the active (i.e., dark) phase of their circadian cycle.
      Similarly, increases in blood enzymatic markers of stress-induced cellular damage
      were less marked following FST exposure in the nocturnal period. Characteristic
      stress-induced increases in 5-HT turnover in the frontal cortex and amygdala
      observed in the diurnal phase were reversed in the nocturnal period. In
      conclusion, circadian differences in behaviour in the FST may be related to
      parallel alterations in the ability of animals to adapt to exposure to stress.

PMID- 10913796
TI  - Chronic low-dose cocaine treatment during adolescence facilitates aggression in
      hamsters.
AB  - Cocaine abuse during adolescence represents a significant health risk because of
      the potential for both acute and long-term negative physical and psychological
      sequelae, including increased aggressive behavior. This study examined the
      effects of chronic adolescent cocaine exposure on aggression in an animal model.
      It was hypothesized that chronic cocaine exposure during adolescence predisposes
      animals to heightened levels of aggressive behavior. To test this hypothesis,
      adolescent male golden hamsters (Mesocricetus auratus) were administered cocaine
      hydrochloride during their entire adolescent development (Postnatal Days 27-54)
      and then tested for offensive aggression using the resident-intruder model.
      Animals treated with low-dose cocaine during adolescence showed significantly
      elevated measures of offensive aggression (i.e., increased number of bites,
      attacks, and decreased latencies to bite), whereas measures of social
      communication, sexual motivation and motor activity remained constant. Cocaine
      treated animals did not differ in body weight gain from controls, suggesting no
      dramatic physiological effects of adolescent cocaine exposure on body growth at
      the doses tested.

PMID- 10913795
TI  - Inhibitory effects of the cannabinoid agonist HU 210 on rat sexual behaviour.
AB  - The present study investigates the effects induced by the cannabinoid agonist HU
      210 (25-100 microg/kg, administered intraperitoneally [i.p.]) on the following
      parameters: (a) sexual behaviour of male rats, categorised on the basis of seven
      consecutive mating pretests as sexually active (SA) and sexually inactive (SI)
      and (b) sexual receptivity of ovariectomised female rats displaying hormonally
      induced heat. The data obtained show that HU 210, administered in acute or
      subchronic mode (once daily for 7 and 14 days), impaired the copulatory pattern
      of SA rats in a dose- and mode-dependent manner, decreasing their sexual drive,
      mainly as represented by an increase in mount and intromission latencies, and
      affecting ejaculation mechanisms (represented as a decrease in intromission
      frequency and increase in ejaculation latency). After subchronic treatment with
      the highest dose had been suspended for 2 weeks, SA males' performance was still
      impaired. In SI rats, acute injections of the drug (25 and 50 microg/kg, i.p.) at
      the higher dose increased contact latency and decreased genital exploration time
      towards the female. Acute HU 210 (25-100 microg/kg, i.p.) also inhibited female
      sexual behaviour, potently reducing lordosis quotient and lordosis intensity.

PMID- 10913797
TI  - Environmental influences on the failure to drink in inbred rats with an ethanol
      preference.
AB  - To investigate the environmental influences on the initiation of voluntary
      consumption of 10% ethanol (EtOH) in rats with differing genetic susceptibility
      to excessive EtOH consumption, Maudsley reactive (MR/Har) and nonreactive
      (MNRA/Har) inbred rats were observed in different types of caging environments.
      Singly housed male and female rats of both strains living in Observational (O)
      cages drank markedly less EtOH during 3 weeks of two-bottle choice than did rats
      living in standard-control (C) individual cages. When male rats had a preexisting
      moderate or heavy pattern of EtOH intake (manipulated through prior EtOH
      experience), moving to the O cage did not reduce EtOH intake. To investigate the
      nature of the above cage effect (the reduced initiation of EtOH consumption), we
      compared the manner in which food had been distributed (traditional food hopper
      in C cages versus loose distribution in O cages) independently of cage type. The
      results showed that MR/Har male rats that obtained food through a hopper in both
      O or C cages drank significantly more EtOH than rats that had food loosely
      distributed in the O or C cages. The results suggest that differences in the mode
      of food procurement and caging can play a large role in whether the phenotype for
      excessive EtOH intake is expressed in the acquisition of an EtOH preference in
      genetically vulnerable rats.

PMID- 10913798
TI  - Effects of space allowance and earthen floor on welfare-related physiological and
      behavioural responses in male blue foxes.
AB  - Welfare-related physiological and behavioural responses were studied in farm-bred
      male blue foxes (Alopex lagopus). Three different-sized cages (80-cm long [CL80],
      120-cm long [CL120], and 240-cm long [CL240]; each 105-cm wide x 70-cm high) with
      wire-mesh floors and one enlarged cage (CL240E) with both wire-mesh floor (240-cm
      long x 105-cm wide x 70-cm high) and earthen floor (80-cm long x 105-cm wide x 70
      cm high) were compared. N = 30 males for each group. The experiments lasted from
      weaning in July to pelting in December. Statistical analyses were based on the
      models accounting for litter as a block effect. Breaking strength of tibia was
      highest for foxes having access to both wire-mesh and ground floors (CL240E).
      Stress-induced hyperthermia was evident during capture and immobilisation. The
      highest rectal temperature (mean +/- SEM) was found in CL240E (capture: 39.6 +/-
      0.09 degrees C, restraint:40.0 +/- 0.09 degrees C) and the lowest in CL80
      (capture: 39.1 +/- 0.09 degrees C, restraint: 39.7 +/- 0.09 degrees C). Likewise,
      capture time (median; interquartile range) in the home cage was highest in CL240E
      (29; 18 to 44) and lowest in CL80 (12; 9 to 14). During capture, foxes tended to
      withdraw to the farthest site within the cage. CL240E foxes typically showed the
      most fear towards human. The most confident animals were found in CL80. The
      cortisol:creatinine ratio (median; interquartile range) obtained from circadian
      urine did not reveal statistically significant differences among CL80 (3. 5; 2.6
      to 4.1), CL120 (2.3; 1.5 to 3.8) and CL240 (2.3, 1.5 to 3.7). The earthen
      flooring complicated the urine sampling and conclusions for CL240E (1.7; 1.2 to
      2.2). CL240E foxes were the most active and explorative on both wire-mesh- and
      ground-floored open-field arenas. Altogether, 53% of furs from CL240E were
      classified as very dirty. Dirtiness of furs in other test groups was slight. In
      conclusion, the present results did not reveal an unambiguous superiority of any
      of the studied cage options for well-being of farmed blue foxes.

PMID- 10913799
TI  - Weanling ventromedial hypothalamic syndrome. bone geometry and biomechanics.
AB  - The effect of growth-retarding, obesifying lesions in the ventromedial
      hypothalamic nucleus (VMN) on bone geometry and biomechanics was investigated in
      male weanling rats. The animals received bilateral, symmetrical, electrolytic
      lesions (VMNL rats) shortly after weanling (age 27 days); sham-operated rats
      served as controls (SCON). The rats were maintained for 42 postoperative days and
      then terminated. Body weight, nose-tail length, food intake, carcass water, and
      lean body mass were all significantly (p < 0.001) reduced in the VMNL group
      compared to SCON rats. Carcass fat, lipogenic efficiency (carcass fat % laid
      down/mean food intake) (both p < 0.001) and epididymal fat pad weight (p < 0.01)
      were significantly increased in VMNL versus SCON. Femur length, anteroposterior
      diameter (both p < 0.001), and mediolateral femur diameter (p < 0.01) were
      significantly reduced in VMNL versus SCON rats, but torque and angle of torque
      were comparable among the groups. VMNL rats femora also showed a significant
      greater maximum shear stress compared to the control animals. The reduced
      parameters in the VMNL rats are in good agreement with the previously
      demonstrated reduced plasma and pituitary growth hormone levels found in this
      hypothalamus preparation.

PMID- 10913800
TI  - Attitudes of Australian veterinarians about the cause and treatment of lower
      respiratory-tract disease in racehorses.
AB  - A questionnaire was administered to members of the Australian Equine Veterinary
      Association to investigate their attitudes and behaviours regarding the cause,
      diagnosis and treatment of lower-respiratory-tract disease in racehorses. The
      most-important perceived risk factors related to the level of exposure and
      resistance to infectious agents, whereas factors associated with racing and
      climatic factors were lower ranked. By far the most-commonly implicated primary
      cause of disease was respiratory viruses. However, specific diagnostic tests
      (such as viral serology or virus isolation) were rarely performed. By far the
      most-common diagnostic procedure was auscultation (without a rebreathing bag).
      The relative importance of diagnostic procedures was influenced by the proportion
      of total workload comprising horse work. Many respondents believed that bacteria
      become secondarily involved in disease; accordingly, antibiotic therapy was the
      most-commonly reported therapy. However, bacteriology of lower-airway-fluid
      samples was not commonly performed. The most-commonly used antibiotics were the
      potentiated sulphonamides (either alone or in combination with mucolytics or
      bronchodilators), followed by procaine penicillin and penicillin combined with
      gentamicin. Mainly, treatment would appear to be based on empirical beliefs
      rather than exhaustive investigation of individual cases.

PMID- 10913801
TI  - Issues associated with the application to veterinarians of a mailed questionnaire
      regarding lower respiratory-tract disease in racehorses.
AB  - This study evaluated a questionnaire investigating the attitudes and behaviours
      of veterinarians regarding the cause, diagnosis and treatment of lower
      respiratory-tract disease in racehorses. The questionnaire was sent to all non
      student members (648) of the Australian Equine Veterinary Association: two
      mailings and a single telephone contact (each separated by four weeks).
      Subsequent phases were only administered to those who had not responded to
      earlier phases. In total, 467 (72.1%) of the 648 mailed questionnaires were
      returned. Of these, 354 were usable. The remaining 113 respondents gave various
      reasons for not completing the questionnaire; the most common (68%) was that
      horses were not a component of their practice. Those respondents working
      primarily with horses required fewer phases to return the questionnaire. Although
      deviating from previously described questionnaire designs, the described protocol
      provided a reasonable response rate.

PMID- 10913802
TI  - The effect of subclinical Mycobacterium paratuberculosis infection on days open
      in Michigan, USA, dairy cows.
AB  - A prospective cohort study design was used to evaluate the impact of subclinical
      Mycobacterium paratuberculosis infection on days open in a sample of Michigan
      dairy herds with a history of cows positive for M. paratuberculosis diagnosed by
      fecal culture. Participating herds were tested and productivity and reproduction
      records were monitored for 18 months. All cows > or = 24 months old were tested
      for M. paratuberculosis infection using the ELISA and radiometric fecal-culture
      (RFC) techniques. Test-negative cows were re-tested at the conclusion of the
      monitoring period. Multivariable regression models were used. Using both tests in
      parallel, the overall sample apparent prevalence for M. paratuberculosis
      infection was 41.8% (223/533 animals tested). Adjusting for diagnostic
      sensitivity and specificity, this resulted in a calculated sample true prevalence
      of 59.9%. ELISA-positive cows (on average) had a 28-day increase in days open
      when compared to ELISA-negative cows (p=0.02). The diagnostic method used to
      define a case altered the apparent association between paratuberculosis test
      status and days open. Fecal culture was a less-effective diagnostic tool for use
      in herds with a high prevalence of infected animals. The increase in days open in
      the ELISA-positive cows was an indication that perhaps reduced estrus expression
      or an increased post-partum anestrous period occurred in the subclinically
      infected ELISA-positive animals. This might have been due to a negative energy
      balance associated with M. paratuberculosis infection.

PMID- 10913804
TI  - Dairy-heifer management in the Netherlands.
AB  - The objective of this study was to describe the Dutch rearing performance of
      dairy heifers by the evaluation of performance indices at weaning, breeding and
      calving. The second objective was to determine the extent to which dairy farmers
      use pre-set rearing targets and data monitoring for the evaluation of their
      rearing results. A questionnaire was sent to 3000 randomly chosen dairy cattle
      farmers to survey their heifer-rearing practices. Almost a third of the farmers
      (n=959) completed and returned the questionnaire. Of the farms responding, 29%
      realised an age at first calving of < or =24 months, 51% from 25 to 27 months,
      and 20% of > or =27 months. The farmers indicated that the average body weight
      after calving was within the range 525-550 kg. Average wither height class was
      141-145 cm. Most farmers estimated the body-condition score of their heifers at
      calving to be 3-3.5. In 29% of the cases, weaning occurred at an age of < or =8
      weeks, 35% at 9-10 weeks of age and 36% at > or =11 weeks of age. Most farmers
      (81%) commenced breeding at an age of > or =15 months. Intermediate evaluation of
      the rearing policy by means of performance goals and measurements was limited,
      and many of the reported performance indices on age and body weight were outside
      the range of the recommended target values. These results indicated that the
      common Dutch heifer-rearing management system could be improved considerably.

PMID- 10913803
TI  - A cross-sectional study of risk factors for obesity in cats in New Zealand.
AB  - This study was done to identify risk factors for obesity in an urban cat
      population in New Zealand. A door-to-door survey (conducted within the city
      limits of Palmerston North) obtained information on the diet, health and
      behaviour of 202 cats. One hundred and eighty-two of these cats were weighed and
      their back and leg lengths were measured. The interviewer's assessment of the
      body condition of each cat was the dependent variable used in this study.
      Variables that were identified as significant (p< or =0.1) following univariable
      analysis were grouped into one of the three models for stepwise logistic multiple
      regression (one each for cat characteristics, environmental and management
      variables and feeding variables). A combined logistic-regression analysis was
      performed on the significant variables identified from the three component
      models. In the combined model, only three variables were significant: the
      presence of dogs in a household (decreased odds of obesity), longer leg length
      and owners underestimating cats' body condition (both increased odds).

PMID- 10913805
TI  - A longitudinal study of campylobacter infection of broiler flocks in Great
      Britain.
AB  - One hundred flocks associated with five integrated poultry companies were
      monitored for one production cycle to investigate risk factors for campylobacter
      infection of poultry broiler flocks. Bacteriological samples were collected from
      one house of birds on each site at weekly intervals from 3 to 4 weeks of age
      until the birds were infected with campylobacter or the flock was depopulated
      (whichever was sooner). Environmental samples were obtained from 20 houses after
      cleansing and disinfection of the site before chick arrival. Conventional methods
      were used for the isolation of campylobacter. Questionnaires were used to collect
      information on potential risk factors for campylobacter infection. Discrete-time
      survival analysis was used to assess the influence of various exposures on the
      age at which the flock was infected with campylobacter. More than 40% of flocks
      were infected with campylobacter by the time the chicks were 4 weeks old and >90%
      by 7 weeks. Infection spread rapidly to most birds in a flock. Infection was not
      predictable by campylobacter status of the last flock reared on the site.
      (However, because most flocks were infected, the power to detect such an
      association was poor.) There was no evidence of environmental survival of
      campylobacters in broiler houses after adequate cleansing and disinfection. The
      most important predictors of protection from campylobacter were related to
      effective hygiene barriers (such as housing birds in buildings in a good state of
      repair, appropriate usage of disinfectant boot dips and a high standard of
      cleansing and disinfection of the drinking-water equipment). There was no
      evidence that rodents were a source of infection (but most sites operated
      effective vermin-control programmes).

PMID- 10913806
TI  - Power calculation for clinical trials when the outcome is a composite ranking of
      survival and a nonfatal outcome.
AB  - In a clinical trial in which mortality occurs and a nonfatal outcome is measured
      after a fixed duration of follow-up, composite rank scores in which deaths
      (ranked by survival time) are scored below ranks for the nonfatal outcome have
      been proposed to test for treatment efficacy. This report derives formulae for
      calculating power for such a rank test under the conservative assumption that the
      treatment has a beneficial effect on the nonfatal outcome but no effect on
      mortality.

PMID- 10913807
TI  - Estimating significance level and power comparisons for testing multiple
      endpoints in clinical trials.
AB  - Clinical trials generally include several outcome measures of interest for
      assessing treatment efficacy and harm. Traditionally a single measure, the
      primary outcome, is selected and used as the basis for the design, including
      sample size and power. Secondary outcomes are then generally ordered with respect
      to their clinical relevance and importance. While this has become the traditional
      paradigm, recent trials have suggested the need for additional approaches. In
      this setting, two outcomes are viewed as key, either one being sufficient for
      proof of efficacy, but with an ordering of preference. The basic question, in
      such cases, is how to control the overall significance level for the trial. We
      describe and compare two methods for testing primary and secondary endpoints,
      accounting for their hierarchical nature-the ordering preference. Both methods
      are sequential, in the sense that the secondary endpoint is only tested when the
      primary outcome fails to reach significance. The first method uses a global test
      for the combination of the primary and secondary endpoints, while the second uses
      a partial Bonferroni correction. Simulation results indicate that the Bonferroni
      adjustment method performs as well as the global test method in most cases, and
      even better in some cases.

PMID- 10913808
TI  - How to select covariates to include in the analysis of a clinical trial.
AB  - The comparisons of treatments in randomized clinical trials may use the analysis
      of covariance to adjust for patient characteristics. We present theoretical
      results that describe when such an adjustment would be expected to be beneficial.
      A distinction is made between covariates that are balanced in the design and
      those that are assigned by the randomization process. The results support the
      commonly held view that features balanced in the design of the trial (e.g., by
      stratification) and those that are strongly predictive of the outcome, and thus
      considered clinically prognostic, should normally be included in the analysis.
      For other covariates that are not balanced in the design, the potential benefits
      of including them in the analysis will depend on the number of patients in the
      trial. However, there is frequently a set of variables whose relevance is unknown
      and for which data-dependent methods of selection, based on the data for the
      current trial, have been proposed. A review of the literature has shown that
      these methods can produce misleading inferences. The decision as to which
      covariates to include in the analysis should be specified in the protocol on the
      basis of data from previous trials on similar patient populations. The methods
      are illustrated with data from a trial comparing two therapies for treating scalp
      psoriasis where the clinical importance of patients' age and sex as prognostic
      factors for efficacy is unknown. We show for what size of future trials it would
      be beneficial to adjust for these covariates and for what size trials it would
      not. In all cases, prespecification of variables to be included in the analysis
      is essential in order to avoid bias.

PMID- 10913809
TI  - Phase II clinical trial design for noncytotoxic anticancer agents for which time
      to disease progression is the primary endpoint.
AB  - Phase II evaluation is a critical screening step in the development of new cancer
      treatments. Historically, anticancer agents have been cytotoxic; they kill
      existing cells. As such, the primary endpoint for phase II evaluation has been
      tumor response rate, the percentage of patients whose tumors shrink > 50%.
      Biotechnology has led to promising new anticancer agents that are cytostatic. In
      contrast to cytotoxics, these agents modulate tumor environments and/or cellular
      targets and are expected to delay tumor growth. Phase II evaluation of such
      agents may instead focus on failure-time endpoints, such as time to disease
      progression. We examine a phase II trial design that evaluates clinical benefit
      by comparing sequentially measured paired failure times within each treated
      patient. Clinical efficacy is defined by a hazard ratio. Assuming patients
      eligible for a phase II study of a new cytostatic agent have failed previous
      cancer treatment, their most recent prior time to progression interval, TTP(1),
      is uncensored. Time to progression after the cytostatic agent, TTP(2), may or may
      not be censored at analysis. The design is motivated by a "growth modulation
      index" (TTP(2)/TTP(1)) and the proposition that a cytostatic agent be considered
      effective if the index is greater than 1.33. A chi(2) test statistic is employed
      to evaluate the paired failure-time data (TTP(1), TTP(2)). The degree of
      correlation between the paired failure times is a key feature of this design.
      Power of the test was evaluated through simulation of trials. Assuming a null
      hazard ratio equal to 1.0, a trial designed to detect an alternative hazard ratio
      equal to 1.3, based on accrual of 25 patients/year for 2 years (50 patients
      total) and with an additional 2 years of follow-up, has 25%, 46%, and 83% power
      based on correlations of 0.3, 0.5 and 0.7, respectively. These results
      demonstrate efficiency of the trial design, given moderate to strong correlations
      between paired failure times.

PMID- 10913810
TI  - The phase II/III transition. Toward the proof of efficacy in cancer clinical
      trials.
AB  - Few phase III investigations show a benefit for an experimental treatment when
      compared to a standard therapy or placebo. This illustrates the need for more
      reliable estimates of treatment effects from the phase II investigations used to
      design the more definitive phase III trials. In this manuscript, we examine four
      aspects of phase II clinical trial designs: (1) selecting endpoints; (2) defining
      the patient population for evaluation; (3) determining a level of activity that
      would justify a phase III trial; and (4) estimating sample sizes. In each area,
      problems with the conventional approaches are discussed and alternatives for the
      successful transition of phase II results to a phase III setting are suggested.
      An application of the design for patients with androgen-independent prostate
      cancer is illustrated.

PMID- 10913811
TI  - Estimating a treatment effect with the accelerated hazards models.
AB  - In randomized clinical trials, when the outcome of interest is time to event, the
      proportional hazards model or the accelerated failure time model is often used to
      identify a treatment effect. In this article, we discuss a simple alternative
      called the accelerated hazards model in which the treatment effect is
      characterized as the hazard progression time ratio, when the treatment is
      believed to accelerate or decelerate the underlying hazard progression through
      time. Survival data from an actual randomized placebo-controlled trial, which
      evaluates the effectiveness of biodegradable polymers with carmustine to treat
      malignant gliomas, is used for illustration.

PMID- 10913812
TI  - Impact of the Hawthorne effect in a longitudinal clinical study: the case of
      anesthesia.

PMID- 10913813
TI  - Letter to the editor

PMID- 10913814
TI  - The non-insulin-dependent diabetes, hypertension, microalbuminuria or
      proteinuria, cardiovascular events, and ramipril (DIABHYCAR) study: design,
      organization, and patient recruitment. DIABHYCAR Study Group.
AB  - The non-insulin-dependent DIABetes, HYpertension, microalbuminuria or
      proteinuria, CARdiovascular events, and Ramipril (DIABHYCAR) study is a
      randomized, prospective, double-blind, placebo-controlled, multicenter
      international trial of the ACE inhibitor ramipril (1.25 mg/day) in patients with
      type II diabetes and micro- or macroalbuminuria. The main outcome of the study is
      the time to first occurrence of either death from a cardiovascular origin,
      including sudden death, nonfatal myocardial infarction, stroke, or congestive
      heart failure, or requirement of hemodialysis or renal transplantation. The study
      was launched in France in early 1995 with the participation of general
      practitioners only, but had to be extended to 15 other countries in 1997 due to
      difficulties in recruitment. Since 2.5 years after the beginning of the trial the
      observed event rate was much less than anticipated, it was decided to increase
      recruitment and follow-up duration and to include congestive heart failure in the
      definition of the main outcome to keep the study power at a satisfactory level.
      Recruitment ended on April 1, 1998 with 4937 randomized patients. Following the
      early discontinuation for efficacy of another study of ramipril in high
      cardiovascular risk patients, the Heart Outcomes Prevention Evaluation study
      (HOPE), the second interim analysis of DIABHYCAR was performed early (when 406
      instead of 500 patients presented a main outcome) and the Data Safety and
      Monitoring Board recommended that the study continue. Follow-up is planned to end
      on March 31, 2001.

PMID- 10913815
TI  - Multicenter radial artery patency study (RAPS). Study design.
AB  - The use of an internal thoracic artery rather than a saphenous vein graft for
      left anterior descending coronary artery bypass is associated with improved long
      term outcome. Hence, expanded use of arterial conduits for other coronary targets
      has been advocated. The radial artery possesses a number of anatomic features
      that are technically advantageous compared with other arterial conduits. This
      study will determine the relative patency of the radial artery compared to the
      saphenous vein for right and circumflex coronary bypass. Patients with graftable
      multivessel coronary disease and an estimated left ventricular ejection fraction
      >/= 35% undergoing nonemergent primary isolated coronary bypass surgery are
      eligible. The right and circumflex vessels must have high-grade lesions (>/= 70%
      diameter stenosis), with target segments of reasonable quality >/= 1.5 mm in
      diameter. Patients serve as their own controls. The radial artery is randomly
      allocated to bypass the right or circumflex territory and a saphenous vein is
      used for the nonradial site. An internal thoracic artery is used for the left
      anterior descending coronary artery in all cases. Randomization is stratified by
      center. The primary study endpoint is graft patency as determined by angiography,
      8-12 months postoperatively. The relative patency of the radial artery compared
      with the saphenous vein will be determined using McNemar's test. A sample size of
      464 patients will provide 80% power for a two-tailed test (alpha = 0.05) for a
      40% relative reduction in the rate of distal anastomotic occlusion from 12% in
      the saphenous vein to 7.2% in the radial arteries assuming a 20% within-patient
      correlation. A single interim analysis will be performed following completion of
      232 angiograms. To allow for lack of follow-up angiography in up to 20% of
      enrolled patients, we plan to randomize a total of 560 patients. It is also our
      intention to assess the long-term patency (5-10 years) of radial artery relative
      to saphenous vein grafts in follow-up studies. Three hundred patients were
      recruited from 12 Canadian, university-affiliated sites from November 1996 until
      February 1999, of which 128 patients have undergone follow-up angiography.
      Approximately 80% of those who have been followed for more than 1 year have
      undergone follow-up angiography. This trial will determine the 8-12 month patency
      of the radial artery relative to the saphenous vein for non-left anterior
      descending coronary bypass using a novel study design which helps control for
      potential bias from individual patient and vessel factors. Positive results would
      support the use of the radial artery in particular, and multiple arterial grafts
      in general.

PMID- 10913817
TI  - Pyruvate carboxylase from Mycobacterium smegmatis: stabilization, rapid
      purification, molecular and biochemical characterization and regulation of the
      cellular level.
AB  - This is the first report on the purification and characterization of an
      anaplerotic enzyme from a Mycobacterium. The anaplerotic reactions play important
      roles in the biochemical differentiation of mycobacteria into non-replicating
      stages. We have purified and characterized a pyruvate carboxylase (PYC) from
      Mycobacterium smegmatis and cloned and sequenced its gene. We have developed a
      very rapid and efficient purification protocol that provided PYC with very high
      specific activities (up to 150 U/mg) that remained essentially unchanged over a
      month. The enzyme was found to be a homomultimer of 121 kDa subunits, mildly
      thermophilic, absolutely dependent on acyl-CoAs for activity and inhibited by
      ADP, by excess Mg(2+), Co(2+), and Mn(2+), by aspartate, but not by glutamate and
      alpha-ketoglutarate. Supplementation of minimal growth medium with aspartate did
      not lower the cellular PYC level, rather doubled it; with glutamate the level
      remained unchanged. These observations would not fit the idea that the M.
      smegmatis enzyme fulfills a straightforward anaplerotic function; in a closely
      related organism, Corynebacterium glutamicum, PYC is the major anaplerotic
      enzyme. Growth on glucose provided 2-fold higher cellular PYC level than that
      observed with glycerol. The PYCs of M. smegmatis and Mycobacterium tuberculosis
      were highly homologous to each other. In M. smegmatis, M. tuberculosis and M.
      lepra, pyc was flanked by a putative methylase and a putative integral membrane
      protein genes in an identical operon-like arrangement. Thus, M. smegmatis could
      serve as a model for studying PYC-related physiological aspects of mycobacteria.
      Also, the ease of purification and the extraordinary stability could make the M.
      smegmatis enzyme a model for studying the structure-function relationships of
      PYCs in general. It should be noted that no crystal structure is available for
      this enzyme of paramount importance in all three domains of life, archaea,
      bacteria, and eukarya.

PMID- 10913818
TI  - Novel compounds, '1,3-selenazine derivatives' as specific inhibitors of
      eukaryotic elongation factor-2 kinase.
AB  - The inhibitory activities of 5,6-dihydro-4H-1,3-selenazine derivatives on protein
      kinases were investigated. In a multiple protein kinase assay using a postnuclear
      fraction of v-src-transformed NIH3T3 cells, 4-ethyl-4-hydroxy-2-p-tolyl-5, 6
      dihydro-4H-1,3-selenazine (TS-2) and 4-hydroxy-6-isopropyl-4-methyl-2-p-tolyl-5,6
      dihydro-4H-1, 3-selenazine (TS-4) exhibited selective inhibitory activity against
      eukaryotic elongation factor-2 kinase (eEF-2K) over protein kinase A (PKA),
      protein kinase C (PKC) and protein tyrosine kinase (PTK). In further experiments
      using purified kinases, TS-2 (IC(50)=0.36 microM) and TS-4 (IC(50)=0.31 microM)
      inhibited eEF-2K about 25-fold more effectively than calmodulin-dependent protein
      kinase-I (CaMK-I), and about 6-fold (TS-2) or 33-fold (TS-4) more effectively
      than calmodulin-dependent protein kinase-II (CaMK-II), respectively. TS-2 and TS
      4 showed much weaker inhibitory activity toward PKA and PKC, while TS-4, but not
      TS-2, moderately inhibited immunoprecipitated v-src kinase. TS-2 (10.7-fold) and
      TS-4 (12.5-fold) demonstrated more potent and more specific eEF-2K inhibitory
      activity than rottlerin, a previously identified eEF-2K inhibitor. TS-2 inhibited
      ATP or eEF-2 binding to eEF-2K in a competitive or non-competitive manner,
      respectively. In cultured v-src-transformed NIH3T3 cells, TS-2 also decreased
      phospho-eEF-2 protein level (IC(50)=4.7 microM) without changing the total eEF-2
      protein level. Taken together, these results suggest that TS-2 and TS-4 are the
      first identified selective eEF-2K inhibitors and should be useful tools for
      studying the function of eEF-2K.

PMID- 10913820
TI  - Effects of lithium and insulin on glycogen synthesis in L6 myocytes: additive
      effects on inactivation of glycogen synthase kinase-3.
AB  - In insulin-sensitive L6 myocytes, insulin stimulated glycogen synthesis in a dose
      dependent manner and lithium further stimulated glycogen synthesis at all insulin
      concentrations. Lithium alone at 20 mM stimulated glycogen synthesis to the
      degree similar to the maximal insulin response. Effects of lithium and insulin
      were fully additive for both glycogen synthesis and glycogen synthase activity.
      In L6 myocytes, insulin increased phosphorylation of Akt1 and glycogen synthase
      kinase-3 alpha and beta (GSK-3 alpha and beta), resulting in its activation and
      inactivation, respectively. Unlike insulin, lithium directly inhibited GSK-3
      (both alpha and beta) without affecting phosphorylation of GSK-3. Moreover,
      lithium in vitro could further inhibit enzyme activity of GSK-3 (both alpha and
      beta) that was isolated from insulin-stimulated cells (thus already
      phosphorylated and inactivated by insulin). In summary, insulin increases
      glycogen synthesis by the Akt1/GSK-3/glycogen synthase pathway, but lithium
      increases glycogen synthesis by direct inhibition of GSK-3 in L6 myocytes.
      Inhibitory effects of lithium and insulin on GSK-3 (both alpha and beta) were
      additive, which may account, at least in part, for their additive effects on
      glycogen synthase activity and glycogen synthesis in L6 myocytes.

PMID- 10913819
TI  - A new lectin in red kidney beans called PvFRIL stimulates proliferation of NIH
      3T3 cells expressing the Flt3 receptor.
AB  - A new legume lectin has been identified by its ability to specifically stimulate
      proliferation of NIH 3T3 fibroblasts expressing the Flt3 tyrosine kinase
      receptor. The lectin was isolated from conditioned medium harvested from human
      peripheral blood mononuclear cells activated to secrete cytokines by a crude red
      kidney bean extract containing phytohemagglutinin (PHA). Untransfected 3T3 cells
      and 3T3 cells transfected with the related Fms tyrosine kinase receptor do not
      respond to this lectin, which we called PvFRIL (Phaseolus vulgaris Flt3 receptor
      interacting lectin). When tested on cord blood mononuclear cells enriched for
      Flt3-expressing progenitors, purified PvFRIL fractions maintained a small
      population of cells that continued to express CD34 after 2 weeks in suspension
      cultures containing IL3. These cultures did not show the effects of IL3's strong
      induction of proliferation and differentiation (high cell number and exhausted
      medium); instead, low cell number at the end of the culture period resulted in
      persistence of cells in the context of cell death. These observations led to the
      hypothesis that PvFRIL acts in a dominant manner to preserve progenitor viability
      and prevent proliferation and differentiation.

PMID- 10913821
TI  - Terminal glycosylation of bovine uroplakin III, one of the major integral
      membrane glycoproteins of mammalian bladder.
AB  - Uroplakin III (UPIII) is one of the major transmembrane glycoproteins exposed at
      the luminal face of mammalian bladder. We investigated the terminal glycosylation
      of bovine UPIII in order to ascertain whether it contains the alpha 2,3
      sialylated sequence thus potentially serving as a receptor for uropathogenic
      Escherichia coli expressing type S adhesins. We report the occurrence of sialic
      acid in alpha 2,3- and alpha 2,6-linkage to galactose in bovine UPIII glycans as
      evidenced by the sensitivity of UPIII to both Vibrio cholera and Newcastle
      disease virus neuraminidase and by the colocalization of UPIII antigen and
      material detected by lectins of Sambucus nigra and Maackia amurensis on the
      luminal face of the bladder. We also present evidence that UPIII glycans are
      capped by Gal-alpha 1,3-Gal epitope. Consistently, alpha 2,3- and alpha 2, 6
      sialyltransferase, as well as alpha 1,3-galactosyltransferase were found to be
      present in the cells detached from the luminal side of bovine bladder, which are
      responsible for the UPIII biosynthesis. The putative role of UPIII sialylated
      glycans in enhancing the uropathogenicity of E. coli expressing type S adhesins
      is discussed.

PMID- 10913822
TI  - Are Kupffer cells involved in the metabolic adaptation of the liver to dietary
      carbohydrates given after fasting?
AB  - In rats, a high carbohydrate fat-free (HCFF) diet, given after fasting, induces
      both hepatic lipogenic and glycogenic enzymes. In the present study, we evaluated
      the involvement of Kupffer cells in the metabolic events occurring in the liver
      during the fasting-refeeding transition. Male Wistar rats were fasted for 48 h
      and received an intravenous injection of either NaCl 0.9% (Gd-) or 10 mg/kg
      GdCl(3) (Gd+), an inhibitor of Kupffer cells, then fed for 12 h with a HCFF diet.
      The comparison of colloidal carbon uptake was similar in rats fasted and in rats
      fasted and then refed a HCFF diet, thus indicating that refeeding does not affect
      per se Kupffer cell phagocytic activity. The inhibition of Kupffer cells by
      GdCl(3) did not affect fatty acid synthase (FAS) induction, as shown by the
      analysis of both FAS mRNA and activity; refeeding a HCFF diet increased the
      hepatic triglyceride and glycogen content to the same extent in Gd+ and Gd- rats.
      Our results do not support the involvement of Kupffer cells in the metabolic
      events occurring in the liver tissue by feeding a HCFF diet after fasting.
      However, the discussion supports the involvement of Kupffer cells in the
      modulation of the hepatic lipid metabolism by other nutrients than carbohydrates.

PMID- 10913823
TI  - Influence of hydrophilicity of cationic polymers on the biophysical properties of
      polyelectrolyte complexes formed by self-assembly with DNA.
AB  - To investigate the possibility of producing charge-neutral gene delivery
      complexes with extended, non-particulate structures, DNA was allowed to self
      assemble with a series of hydrophilic cationic polymers containing quaternary
      charged trimethylammonio ethylmethacrylate (TMAEM, 5, 15, 50, 100 mol%)
      copolymerised with hydrophilic N-(2-hydroxypropyl)methacrylamide (HPMA, 95, 85,
      50, 0 mol%, respectively). Copolymers were all able to bind DNA, assessed using
      ethidium bromide fluorescence, although copolymers with low TMAEM content did not
      expel ethidium bromide. Increasing TMAEM content of the copolymers changed the
      morphology of the complexes from extended (5-15 mol% TMAEM), through partially
      condensed particles (50 mol%) to discrete nanoparticles (100 mol% TMAEM).
      Complexes based on copolymers with low TMAEM content (5-50 mol%) showed less
      resistance to degradation by nucleases and lower surface charge (21.2+/-5.9
      45.1+/-3.9 mV) than those formed using 100 mol% TMAEM (57.8+/-8.2 mV). They also
      showed significantly less association with phagocytic cells in vitro (human
      leucocytes, uptake decreased by up to 92.3%; murine peritoneal macrophages,
      uptake decreased by up to 69.6%), although in vivo their hepatic accumulation was
      only slightly decreased (maximum decrease 27.6%). Finding the appropriate balance
      of hydrophilicity and stability is key to development of effective vectors for
      gene delivery.

PMID- 10913824
TI  - Hydroperoxide specificity of plant and human tissue lipoxygenase: an in vitro
      evaluation using N-demethylation of phenothiazines.
AB  - Since hydroperoxide specificity of lipoxygenase (LO) is poorly understood at
      present, we investigated the ability of cumene hydroperoxide (CHP) and tert-butyl
      hydroperoxide (TBHP) to support cooxidase activity of the enzyme toward the
      selected xenobiotics. Considering the fact that in the past, studies of
      xenobiotic N-demethylation have focused on heme-proteins such as P450 and
      peroxidases, in this study, we investigated the ability of non-heme iron
      proteins, namely soybean LO (SLO) and human term placental LO (HTPLO) to mediate
      N-demethylation of phenothiazines. In addition to being dependent on peroxide
      concentration, the reaction was dependent on enzyme concentration, substrate
      concentration, incubation time, and pH of the medium. Using Nash reagent to
      estimate formaldehyde production, the specific activity under optimal assay
      conditions for the SLO mediated N-demethylation of chlorpromazine (CPZ), a
      prototypic phenothiazine, in the presence of TBHP, was determined to be 117+/-12
      nmol HCHO/min/mg protein, while that of HTPLO was 3.9+/-0.40 nmol HCHO/min/mg
      protein. Similar experiments in the presence of CHP yielded specific activities
      of 106+/-11 nmol HCHO/min/mg SLO, and 3.2+/-0.35 nmol HCHO/min/mg HTPLO. As
      expected, nordihydroguaiaretic acid and gossypol, the classical inhibitors of
      LOs, as well as antioxidants and free radical reducing agents, caused a marked
      reduction in the rate of formaldehyde production from CPZ by SLO in the reaction
      media fortified with either CHP or TBHP. Besides chlorpromazine, both SLO and
      HTPLO also mediated the N-demethylation of other phenothiazines in the presence
      of these organic hydroperoxides.

PMID- 10913825
TI  - The VIG9 gene products from the human pathogenic fungi Candida albicans and
      Candida glabrata encode GDP-mannose pyrophosphorylase.
AB  - We have identified two genomic DNA fragments from the human pathogenic fungi,
      Candida albicans (CaVIG9) and Candida glabrata (CgVIG9) that encode GDP-mannose
      pyrophosphorylase, a key enzyme for protein glycosylation. The VIG9 homologues of
      CaVIG9 and CgVIG9 complement an identified protein glycosylation-defective
      mutation, vig9, of Saccharomyces cerevisiae. The nucleotide sequences of the
      ORFs, which are 83 and 90% identical to that of the ScVIG9 protein, respectively,
      showed a predicted gene product homologous to S. cerevisiae GDP-mannose
      pyrophosphorylase. We examined the enzyme activity of a glutathione S-transferase
      fusion of each VIG9 gene to synthesize GDP mannose in the cell extracts of a
      heterologous Escherichia coli expression system. We also developed a method for
      detecting the enzyme activity using a non-radioactive substrate that would be
      applicable to high throughput screening.

PMID- 10913826
TI  - The bystander effect in photodynamic inactivation of cells.
AB  - Treatment of MDCK II cells with the lipophilic photosensitizer tetra(3
      hydroxyphenyl)porphyrin and light was found to induce a rapid apoptotic response
      in a large fraction of the cells. Furthermore, the distribution of apoptotic
      cells in microcolonies of eight cells was found to be different from the binomial
      distribution, indicating that the cells are not inactivated independently, but
      that a bystander effect is involved in cell killing by photodynamic treatment.
      The observation of a bystander effect disagrees with the common view that cells
      are inactivated only by direct damage and indicates that communication between
      cells in a colony plays a role in photosensitized induction of apoptosis. The
      degree of bystander effect was higher for cells dying by necrosis than for cell
      dying by apoptosis.

PMID- 10913827
TI  - Detection of thiol modification following generation of reactive nitrogen
      species: analysis of synaptic vesicle proteins.
AB  - S-nitrosylation is an important means of regulating the activity of proteins. We
      have developed a method which allows unbiased identification of thiol modified
      proteins within a complex mixture following NO generation, by taking advantage of
      the fact that prior nitrosylation will block subsequent modification of cysteine
      residues with 1-biotinamido-4-[4'-(maleimidomethyl)-cyclohexane-carboxamid o]
      butane (biotin-BMCC). Thiol modified proteins are reduced in intensity when
      revealed by blotting and overlay with avidin-horseradish peroxidase. In the case
      of a purified synaptic vesicle fraction we observe a high degree of enrichment of
      specific biotinylated proteins relative to homogenate. We find that thiol
      modification of proteins in the presence of NO donors is widespread, occurring in
      the majority of proteins that will react with biotin-BMCC. In a further
      development of this technique we have depleted the biotinylated proteins from
      solubilised synaptic vesicles using avidin-agarose and analysed the supernatants
      with a panel of antibodies. This has allowed us to identify SNARE proteins
      (soluble NSF attachment protein receptors) as potential targets for S
      nitrosylation.

PMID- 10913828
TI  - Distribution of sulfated glycosaminoglycans in the animal kingdom: widespread
      occurrence of heparin-like compounds in invertebrates.
AB  - Sulfated glycosaminoglycans were isolated from 23 species of 13 phyla of
      invertebrates and characterized by their electrophoretic migration in three
      different buffer systems coupled with enzymatic degradation using bacterial
      heparinase, heparitinases and chondroitinase AC. Heparan sulfate is a ubiquitous
      compound present in all species analyzed whereas chondroitin sulfate was present
      in 20 species and heparin-like compounds in 12 species of the invertebrates. The
      heparin-like compounds were purified from the echinoderm Mellita
      quinquisperforata (sand dollar) and the crustacean Ucides cordatus (crab) with
      anticoagulant activities of 60 and 52 IU/mg, respectively. Degradation of these
      heparins with heparinase produced significant amounts of the trisulfated
      disaccharide typical of mammalian heparins. This was confirmed by 13C-NMR
      spectroscopy of the crab heparin. An updated phylogenetic tree of the
      distribution of sulfated glycosaminoglycans in the animal kingdom is also
      presented.

PMID- 10913829
TI  - Isolation and characterization of mammalian eumelanins from hair and irides.
AB  - A new enzymatic procedure was developed for isolation of eumelanin from black
      human hair which might provide a substantially intact pigment for structural
      characterization. Sequential digestion with protease, proteinase K and papaine in
      the presence of dithiothreitol afforded a pigment with a 6% w/w protein content.
      HPLC analysis of pyrrole acids resulting from alkaline H(2)O(2) degradation,
      carboxyl content determination, and ferricyanide titration showed that the
      isolated pigment is made up of 5,6-dihydroxyindole (DHI)- and 5, 6
      dihydroxyindole-2-carboxylic acid (DHICA)-derived units at a 6:1 ratio,
      exhibiting a significant degree of oxidative degradation. For comparison, a
      different eumelanin isolated from black bovine irides by a similar enzymatic
      procedure was analyzed. Matrix-assisted laser desorption ionization (MALDI) mass
      spectrometry of the final pigment provided evidence for homologous series of
      DHICA oligomers, while chemical analysis allowed an estimate of 2:1 DHICA/DHI
      derived units in the polymer, with a substantial proportion of intact o
      diphenolic functions. Iris melanin proved able to promote the Fenton oxidation of
      deoxyribose while hair melanin was ineffective. Overall, these results provide,
      for the first time, unambiguous evidence for marked structural differences of
      mammalian eumelanins which may be directly related to the diversity of the sites
      of biosynthesis and storage, as well as to functional role of these pigments.

PMID- 10913830
TI  - Release of gelonin from endosomes and lysosomes to cytosol by photochemical
      internalization.
AB  - Gelonin, a type I ribosome-inactivating plant toxin, executes N-glycosidase
      activity on eukaryotic ribosomes. However, on intact cells, gelonin is relatively
      non-toxic, due to an incapability to penetrate cell membranes. Recently, a novel
      method, photochemical internalization (PCI), was invented for the translocation
      of membrane-impermeable molecules including gelonin to the cytosol [K. Berg et
      al., Cancer Res. 59 (1999) 1180-1183]. The combination of gelonin and
      photoactivation of endosomal and lysosomal localizing photosensitizers gives
      strong synergistic cytotoxic effects. In this study, we have evaluated the
      intracellular transport and stability of gelonin. By fluorescence microscopy, it
      was shown that gelonin co-localizes with the endosomal and lysosomal localizing
      photosensitizer, aluminum phthalocyanine with two sulfonate groups on adjacent
      phenyl rings, and both molecules re-localized to cytosol subsequently to light
      exposure. Gelonin accumulated in endosomal compartments by incubation at 18
      degrees C was released to cytosol by PCI with concomitant inhibition of protein
      synthesis indicating that PCI can be executed through rupture of endosomal
      vesicles. The cathepsin inhibitor L-trans-epoxysuccinyl-leucyl amido(4
      guanido)butane increased the cytotoxic effect of gelonin after PCI when gelonin
      was provided as a 2 h pulse followed by 4 h chase before PCI. Thus, although
      gelonin can enter the cytosol from lysosomes, lysosomal degradation is a limiting
      factor for the outcome of PCI of gelonin.

PMID- 10913831
TI  - Non-invasive in vivo magnetic resonance imaging assessment of acute aflatoxin B1
      hepatotoxicity in rats.
AB  - Acute aflatoxin B1 (AFB1)-induced hepatotoxicity was assessed in vivo in male
      Sprague-Dawley rats (150-300 g) using magnetic resonance imaging (MRI). MRI
      results were compared to serum enzyme levels, histology and electron microscopy.
      Twenty-four hours following intraperitoneal delivery of AFB1 (3 mg/kg body weight
      in a saline/dimethyl sulfoxide (DMSO; 0.03 ml/kg body weight) solution), regions
      of damage, characterised by increased proton signal intensities in T2-weighted
      images, were observed in the vicinity of the hepatic portal vein (HPV) and in the
      right medial regions of the liver. Image analysis of regions of apparent damage
      around the HPV and right medial regions, following 24 h of AFB1 exposure,
      indicated statistically significant (P<0.05) increases in proton image signal
      intensities, when compared to saline/DMSO-treated rats. No significant difference
      in proton image signal intensities were observed 1-2 h following AFB1 exposure.
      Twenty-four hours following AFB1 exposure, histopathological assessment was
      characterised by portal/central vein/artery congestion, sinusoid congestion,
      nuclear pyknosis and karyolysis, and hepatocyte vacuolation; electron microscopy
      (EM) examination indicated nuclear debris, swollen cytoplasmic compartments,
      vacuolation, and the disappearance of the smooth endoplasmic reticulum, and
      elevated levels of serum aspartate aminotransferase and alanine aminotransferase
      were found to be significantly different (P<0.01) than controls.

PMID- 10913832
TI  - Structural analysis of trisialylated biantennary glycans isolated from mouse
      serum transferrin. Characterization of the sequence Neu5Gc(alpha 2-3)Gal(beta 1
      3)[Neu5Gc(alpha 2-6)]GlcNAc(beta 1-2)Man.
AB  - Five variants of mouse serum transferrin (mTf, designated mTf-I to mTf-V) with
      respect to carbohydrate composition have been isolated by DEAE-cellulose
      chromatography in the following relative percentages: mTf-I: 0.55; mTf-II: 0.79;
      mTf-III: 71.80; mTf-VI: 21. 90 and mTf-V: 4.96. The primary structures of the
      major glycans from mTf-III and mTf-IV were determined by methylation analysis and
      1H-nuclear magnetic resonance (NMR) spectroscopy. All glycans possessed a common
      trimannosyl-N,N'-diacetylchitobiose core. From the glycovariant mTf-III two
      isomers of a conventional biantennary N-acetyllactosamine type were isolated, in
      which two N-glycolylneuraminic acid (Neu5Gc) residues are linked to galactose
      either by a (alpha 2-6) or (alpha 2-3) linkage. A subpopulation of this
      glycovariant contains a fucose residue (alpha 1-6)-linked to GlcNAc-1. The
      structure of the major glycan found in variant mTf-IV contained an additional
      Neu5Gc and possessed the following new type of linkage: Neu5Gc(alpha 2-3)Gal(beta
      1-3)[Neu5Gc(alpha 2-6)]GlcNAc(beta 1-2 )Man(alpha 1-3). In addition to this
      glycan, a minor compound contained the same antennae linked to Man(alpha 1-6). In
      fraction mTf-V, which was found to be very heterogeneous by (1)H NMR analysis,
      carbohydrate composition and methylation analysis suggested the presence of tri'
      antennary glycans sialylated by Neu5Gc alpha-2,6- and alpha-2, 3-linked to the
      terminal galactose residues. In summary, mTf glycans differed from those of other
      analyzed mammalian transferrins by the presence of Neu5Gc and by a Neu5Gc(alpha 2
      6)GlcNAc linkage in trisialylated biantennary structures, reflecting in mouse
      liver, a high activity of CMP-Neu5Ac hydroxylase and (alpha 2-6)GlcNAc
      sialyltransferase.

PMID- 10913833
TI  - Identification of a plausible biosynthetic enzyme for the IM-2-type autoregulator
      in Streptomyces antibioticus.
AB  - Virginiae butanolides (VBs) and IM-2 are members of Streptomyces hormones called
      'butyrolactone autoregulators' which regulate the antibiotic production in
      Streptomyces species at nanomolar concentrations. Cell-free extract of a VB-A
      overproducer, Streptomyces antibioticus NF-18, is capable of catalyzing the final
      step of the autoregulator biosynthesis, namely, the NADPH-dependent reduction of
      6-dehydroVB-A. However, physico-chemical analyses of the purified enzymatic
      products revealed that, in addition to the VB-type isomer [(2R,3R,6S)
      enantiomer], IM-2-type isomers [(2R,3R, 6R)- and (2S,3S,6S)-enantiomers] were
      also produced from (+/-)-6-dehydroVB-A, suggesting the existence of several 6
      dehydroVB-A reductases with respective stereoselectivities. The reductase
      activity of the crude extracts was separated into two activity peaks, peak I
      (major) and peak II (minor), by DEAE-5PW HPLC. Chiral HPLC analyses demonstrated
      that peak I enzyme and peak II enzyme catalyzed the production of (2R,3R,6S),
      (2R,3R,6R) and (2S,3S, 6S) isomers at ratios of 46:1:3.2 and 4.9:1:1.5,
      respectively, indicating clearly that S. antibioticus NF-18 possesses at least
      two 6-dehydroVB-A reductases: one much favored toward VB-A biosynthesis, the
      other with relaxed stereoselectivity capable of synthesizing both VB-type and IM
      2-type autoregulators.

PMID- 10913834
TI  - Hoxb-5 control of early airway formation during branching morphogenesis in the
      developing mouse lung.
AB  - Hox proteins control structural morphogenesis, pattern formation and cell fate in
      the developing embryo. To determine if Hoxb-5 participates in patterning of early
      airway branching during lung morphogenesis, gestational day 11.5 embryonic lung
      cultures were treated with retinoic acid (RA) to up-regulate and antisense
      oligonucleotides to down-regulate Hoxb-5 protein expression. RA (10(-6) M) and
      Hoxb-5 antisense oligonucleotide (20 microM) treatment each significantly
      decreased branching morphogenesis (P<0. 001), but the morphology of branching
      under these conditions was very different. RA-treated lungs had elongated primary
      branches but decreased further branching with increased Hoxb-5 immunostaining in
      subepithelial regions underlying these elongated airways. Western blots confirmed
      that Hoxb-5 protein was increased by 189+/-20% (mean+/-S.E.M., P<0.05) in RA
      treated lungs compared to controls. In contrast, lungs treated with Hoxb-5
      antisense oligos plus RA had foreshortened primary branches with rudimentary
      distal clefts resulting in decreased numbers of primary and subsequent branches.
      Immunohistochemistry confirmed that Hoxb-5 antisense oligos inhibited Hoxb-5
      protein expression even in the presence of RA. We conclude that regional and
      quantitative changes in Hoxb-5 protein expression influence morphogenesis of the
      first airway divisions from the mainstem bronchi. RA-induced alterations in
      branching are mediated in part through regulated Hoxb-5 expression.

PMID- 10913835
TI  - Self-assembled peptide fibers from valylvaline bola-amphiphiles by a parallel
      beta-sheet network.
AB  - A series of dipeptide-based bola-amphiphiles, bis(N-alpha-amide-L-valyl-L-valine)
      1, n-alkane dicarboxylate (n=4-12), have been synthesized. The bola-amphiphiles
      with n=4 and 6 self-assembled to form crystalline solids in water, whereas those
      with n=7-12 produced peptide fibers. FT-IR spectroscopy and X-ray diffraction
      patterns revealed that the peptide fibers have parallel-type beta-sheet networks
      between the valylvaline units. FT-IR deconvolution study of carboxyl regions
      indicated that these crystalline solids and peptide fibers are stabilized by
      interlayer bifurcated and intralayer lateral hydrogen-bond networks between the
      end carboxylic acid groups, respectively.

PMID- 10913836
TI  - Structural and functional studies on an FtsH inhibitor from Bacillus subtilis.
AB  - The small 3 kDa SpoVM protein is essential for development of the spore in
      Bacillus subtilis. Genetic and biochemical experiments have shown that the
      function of SpoVM is to inhibit the proteolytic activity of FtsH during
      sporulation. We have used a combination of genetic and biophysical techniques to
      characterise the role of this small polypeptide. SpoVM was found to be widespread
      in Bacillus as well as in two Clostridia species, suggesting that SpoVM provides
      a common mechanism for inactivating the FtsH protease during spore
      differentiation. Using site-specific mutagenesis, we have identified C-terminal
      residues of SpoVM essential for biological activity. Analysis of SpoVM's
      structure showed that it is able to assume an alpha-helical conformation in the
      presence of a lipid interface which may be important in interacting with FtsH.

PMID- 10913837
TI  - Occurence of GDP-L-fucose: beta-N-acetylglucosamine (Fuc to asn-linked GlcNAc)
      alpha 1,6-fucosyltransferases in porcine, sheep, bovine, rabbit and chicken
      tissues.
AB  - Transgenic animals are a promising source of pharmaceutically-relevant proteins
      or as a source of organs for xenotransplantation. Beside other posttranslational
      modifications, glycosylation has been shown to be a critical parameter for the
      correct function of several glycoproteins. To analyse the contribution of alpha
      1,6-fucosylation to N-glycan variability, we partly purified alpha 1,6
      fucosyltransferase (alpha 1,6-Fuc-T) activities from various tissues (brain,
      lung, heart, liver) of agriculturally-relevant animals (porcine, sheep, bovine,
      rabbit, chicken) and compared some of their biochemical properties. All tissues
      displayed alpha1,6-Fuc-T activity, although at different levels. No differences
      were observed in their stability against chemicals, temperature or time, whereas
      the activities were distinguishable by their pH-optima and their cation
      preferences. Similarities were found for tissues between species. Lung and heart
      enzymes showed a narrow pH-optimum around pH 6.0 and an enhanced activity in the
      presence of divalent cations. alpha 1,6-Fuc-T activities in brain and liver were
      characterised by a broad pH-optimum from 5.5 to 8.0. Some activities of these
      tissues were decreased by the addition of EDTA, while others did not show any
      influence of EDTA or divalent cations. From the significant differences of the
      alpha 1,6-Fuc-T activities in the tissues, it is possible to hypothesise the
      presence of more than one single alpha 1, 6-Fuc-T in mammalian tissues.

PMID- 10913838
TI  - Improved transfection using epithelial cell line-selected ligands and fusogenic
      peptides.
AB  - Synthetic gene transfer vectors can be optimised by combining DNA-binding
      peptides, cell surface receptor ligands, and fusogenic and nuclear localisation
      peptides. We have used the phage display technique to identify ligands of the
      tracheal epithelial cell line CFT-2. The peptides harboured by two phages were
      selected for transfection studies: peptide 7 (GRGDGDV) that contained the
      integrin-binding motif RGD, and peptide 9 (RFDSLKV) that was found in six out of
      24 phages analysed. Both peptides, fused with the DNA-binding peptide P2
      (SPKRSPKRSPKR), enhanced transfection efficiency in cell lines CFT-2, NT-1, NIH
      3T3 and ECV-304. In particular, peptide P2-7 increased transfection efficiency
      from 36. 5% to 44.8% in NIH-3T3 cells and from 10.9% to 14.4% in CFT-2 cells,
      when compared to transfections performed with peptide P2. Two fusogenic peptides,
      HA (GLFEAIAEFIEGGWEGLIEGC) and JTS-1 (GLFEALLELLESLWELLLEA), were then added to
      the complexes and shown to improve transfection efficiency to the same extent.
      For instance, when combined to peptide P2-7, transfection levels of 54.1% and 55.
      2% were attained in NIH-3T3 cells with HA and JTS-1, respectively. The addition
      of the ligands and fusogenic peptides thus allowed us to construct greatly
      improved transfection reagents.

PMID- 10913839
TI  - Role of alpha-helical conformation of histatin-5 in candidacidal activity
      examined by proline variants.
AB  - Human salivary histatin-5 (Hsn-5) is a potent in vitro anticandidal agent. The
      aim of this study was to investigate the importance of alpha-helical structure of
      Hsn-5 for its candidacidal activity. The following three Hsn-5 variants, where
      one or more functionally nonessential residues were replaced with proline (potent
      alpha-helix breaker), were produced by Escherichia coli expression system: H21P
      (1P), H19P/H21P (2P), and E16P/H19P/H21P (3P). The activities of purified
      proteins were determined by candidacidal assays, and the secondary structures by
      circular dichroism (CD) spectroscopy in trifluoroethanol (TFE) that is considered
      the helix-promoting solvent, and lysophosphatidyl-glycerol (LPG) micelles, the
      environment that more closely resembles the biological membranes. Our results
      indicated that 3P variant displayed a candidacidal activity which was similar to
      that of unaltered Hsn-5 (0P), while 1P and 2P variants showed lower cidal
      activity. The CD spectra in TFE indicated that 3P variant has less helical
      characteristics than the 0P, 1P and 2P. These results suggested that the alpha
      helical content of Hsn-5 proline variants does not correlate with the
      candidacidal activity. Further, the CD spectral analysis of peptides in LPG
      micelles indicated the formation of beta-turn structures in 0P and 3P variants.
      In conclusion, 3P variant which exhibited comparable candidacidal activity to 0P
      contains lower percentage of alpha-helical structure than 1P and 2P variants,
      which exhibited lower candidacidal activity. This suggests alpha-helix may not be
      important for anticandidal activity of Hsn-5.

PMID- 10913840
TI  - N-glycosylation site occupancy of rat alpha-1,3-fucosyltransferase IV and the
      effect of glycosylation on enzymatic activity.
AB  - All mammalian alpha-1,3-fucosyltransferases (Fuc-Ts) so far characterized have
      potential N-glycosylation sites, but the role of these sites in enzymatic
      activity or localization has not been investigated. When one member of this
      family, rFuc-TIV, is expressed in bacteria, the unglycosylated form of rFuc-TIV
      has no detectable enzymatic activity. The two potential N-glycosylation sites of
      rFuc-TIV were mutated to determine site occupancy and the effect of site
      occupancy on enzyme activity and targeting of this enzyme. Results obtained with
      singly mutated forms of rFuc-TIV indicate that both sites are occupied in
      mammalian cells. Lack of glycosylation at sites 117-119, 218-220, or both of
      these sites, decreased enzyme activity to approximately 64%, 5% or 1%,
      respectively, of that seen in the unmutated enzyme. These results show that N
      glycosylation is necessary for optimal enzyme activity, with glycosylation at
      site 218-220 playing the major role. However, N-glycosylation does not appear to
      affect the major intracellular location of the enzyme, as immunocytochemistry
      reveals the same perinuclear pattern of staining for the unglycosylated mutants
      as is seen for the wild-type rFuc-TIV in transfected cells.

PMID- 10913841
TI  - The surface of alpha-subunit loop 1 distant from the subunit interface is exposed
      in the hCG lutropin receptor complex.
AB  - Interactions of the placental glycoprotein hormone human choriogonadotropin (hCG)
      with lutropin receptors (LHR) are required for maintenance of early pregnancy.
      Knowledge of how hCG interacts with LHR is useful for understanding the mechanism
      of receptor function, an issue of considerable debate. A large surface of hCG
      remains exposed after the hormone binds the LHR and can be readily detected with
      monoclonal antibodies. Here we show that the surface of hCG alpha-subunit loop 1
      furthest from the beta-subunit interface can also be recognized by a monoclonal
      antibody when hCG is bound to the LHR. This extends the area of hCG known to be
      exposed in the hormone receptor complex, an observation that further restricts
      models of hCG-LHR interaction.

PMID- 10913842
TI  - Chemical characterization of milk oligosaccharides of the polar bear, Ursus
      maritimus.
AB  - Two trisaccharides, three tetrasaccharides, two pentasaccharides, one
      hexasaccharide, one heptasaccharide, one octasaccharide and one decasaccharide
      were isolated from polar bear milk samples by chloroform/methanol extraction, gel
      filtration, ion exchange chromatography and preparative thin-layer
      chromatography. The oligosaccharides were characterized by 1H-NMR as follows: the
      saccharides from one animal: Gal(alpha1-3)Gal(beta1-4)Glc (alpha3'
      galactosyllactose), Fuc(alpha1-2)Gal(beta1-4)Glc (2'-fucosyllactose), Gal(alpha1
      3)[Fuc(alpha1-2)]Gal(beta1-4)Glc (B-tetrasaccharide), GalNAc(alpha1-3)[Fuc(alpha1
      2)]Gal(beta1-4)Glc (A-tetrasaccharide), Gal(alpha1-3)Gal(beta1-4)GlcNAc(beta1
      3)Gal(beta1-4)Glc, Gal(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)GlcNAc(beta1
      3)Gal(beta1-4)Gl c, Gal(alpha1-3)Gal(beta1-4)GlcNAc(beta1-3)[Gal(alpha1
      3)Gal(beta1-4)Glc NAc(beta1-6)]Gal(beta1-4)Glc; the saccharides from another
      animal: alpha3'-galactosyllactose, Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]Glc, A
      tetrasaccharide, GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal(beta1-4)[Fuc(alpha1-3)]Glc (A
      pentasaccharide), Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1
      3)Gal(beta1-4)Gl c, Gal(alpha1-3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1
      3)Gal(beta1-4)[F uc(alpha1-3)]Glc (difucosylheptasaccharide) and Gal(alpha1
      3)Gal(beta1-4)[Fuc(alpha1-3)]GlcNAc(beta1-3)?Gal(alpha1-3) Gal(beta1
      4)[Fuc(alpha1-3)]GlcNAc(beta1-6)?Gal(beta1-4)Glc (difucosyldecasaccharide).
      Lactose was present only in small amounts. Some of the milk oligosaccharides of
      the polar bear had alpha-Gal epitopes similar to some oligosaccharides in milk
      from the Ezo brown bear and the Japanese black bear. Some milk oligosaccharides
      had human blood group A antigens as well as B antigens; these were different from
      the oligosaccharides in Ezo brown and Japanese black bears.

PMID- 10913843
TI  - Distribution of foliar formylated phloroglucinol derivatives amongst Eucalyptus
      species.
AB  - Formylated phloroglucinol compounds (FPCs) in Eucalyptus leaves are important
      determinants of feeding in marsupial folivores and have a wide range of other
      biological actions. We conducted a survey of the occurrence of formylated
      phloroglucinol compounds (euglobals, macrocarpals and sideroxylonals) in acetone
      petrol extracts of 41 species of Eucalyptus from among seven informal subgenera
      growing on the East Coast of Australia. We used electrospray ionisation, Fourier
      transform ion cyclotron resonance mass spectrometry (ESI-FTMS) to search crude
      extracts of eucalypt leaves for molecular weights characteristic of FPC
      compounds. We found masses characteristic of reported FPCs in 27 of the 41
      species examined. The most frequently identified group of compounds was the
      sideroxylonals. Notable was the lack of known FPCs in the informal subgenus
      Monocalyptus.

PMID- 10913844
TI  - The distribution of the phenolic metabolites barbaloin, aloeresin and aloenin as
      a peripheral defense strategy in the succulent leaf parts of Aloe arborescens.
AB  - Aloe arborescens is a large, multi-stemmed shrub. It is used as hedge plants to
      protect agricultural fields or stock and as horticultural plants in gardens. In
      natural habitats it is one of the very common Aloe species along the Indian Ocean
      coast of southern Africa, from the Cape, in the south, to Zimbabwe and Malawi in
      the north. Secondary phenolic metabolites such as barbaloin (Rf 0.31-0.35),
      aloeresin (Rf 0.25-0.3) and aloenin (Rf 0.51-0.55) have been found to be
      distributed in the succulent leaves of Aloe arborescens in a peripheral defense
      strategy. The youngest leaves have the highest content. The terminal third of
      each leaf has the highest content and the basal third, the lowest. Along the leaf
      margins, on the top third and adaxial side, the content is the highest and in the
      base third, the lowest along the leaf center on the abaxial side. Similar
      relative amounts of these three secondary phenolic metabolites were found in the
      different leaf locations. The leaf orientation may affect the total content of
      these three phenols but not their relative amounts in the different parts of the
      leaves. It is possible that the more often the plant parts are damaged by
      consumption by animals such as elephants, kudu or insects, the greater the
      increase of their phenolic metabolites. This increase may reduce or prevent
      further consumption when the content of the metabolites reaches a certain level.
      The plants then have a chance to renew themselves.

PMID- 10913845
TI  - Effects of carbon dioxide and nitrogen fertilization on phenolic content in Poa
      annua L.
AB  - Different but partially overlapping hypotheses have been developed to predict the
      allocation of phenolics in elevated atmospheric CO(2). The carbon-nutrient
      balance hypothesis predicts increased allocation to phenolics due to reduced
      relative availability of nitrogen. The growth-differentiation balance hypothesis
      states that allocation will depend on source and sink strength, while the protein
      competition model predicts that allocation will remain unchanged. We grew Poa
      annua at two CO(2) concentrations in soils of three different nutrient levels.
      Although plant-tissue nitrogen levels were reduced in high CO(2) and
      photosynthetic rate increased, phenolic concentration and biomass allocation
      remained unchanged. We discuss these data in the context of the three models'
      predictions of phenolic allocation in conditions of elevated CO(2).

PMID- 10913846
TI  - Analysis of very long chain polyunsaturated fatty acids using high-performance
      liquid chromatography - atmospheric pressure chemical ionization mass
      spectrometry.
AB  - The presence and identity of very long chain polyunsaturated fatty acids from
      three freshwater crustacean species, Bathynella natans, B. baicalensis and
      Baicalobathynella magna from Lake Baikal and caves of central Europe were
      determined by means of liquid chromatography-mass spectrometry with atmospheric
      pressure chemical ionization (LC-MS with APCI). LC-MS with APCI enabled the
      identification of more than 50 very long chain polyunsaturated fatty acids. These
      acids were described in the crustaceans for the first time, predominantly 26:5n6,
      28:7n6, 30:7n3 and 40:7n6. A hypothesis for the biosynthesis of these acids is
      proposed.

PMID- 10913847
TI  - The secretion of the ventral glands in Cladius, Priophorus and Trichiocampus
      sawfly larvae.
AB  - The volatile secretion from ventral glands of the larvae of Cladius
      pectinicornis, Priophorus morio, P. pallipes and Trichiocampus grandis was found
      to be principally composed of long-chain acetogenins, in majority of the esters
      and hydrocarbons, with more than 15 carbon atoms. The scarcity of more volatile
      compounds may be considered as plesiomorphic for the tribe Cladiini to which the
      four species belong. Further chemotaxonomic significance and chemical ecological
      implications of the glandular secretions are discussed. Moreover, the function of
      the well-developed pubescence covering the body of Cladiini larvae is discussed
      as a part of their defensive mechanism.

PMID- 10913848
TI  - Ferulic acid is bound to the primary cell walls of all gymnosperm families.
AB  - Unlignified primary cell walls containing ester-linked ferulic acid fluoresce
      blue in ultraviolet radiation which changes to green with increased intensity on
      treatment with ammonium hydroxide. Using this fluorescence behaviour, we detected
      ester-linked ferulic acid in the primary cell walls of all 41 species of
      gymnosperms we examined. These species were in 17 families representing all four
      extant classes of gymnosperms. In addition, we obtained cell-wall preparations
      containing >95% primary cell walls from nine gymnosperm species in nine families,
      representing all four extant classes. These preparations were analysed for ester
      linked monomeric phenolic acids. We found ferulic acid (mostly trans) (88
      1,561ug/g cell walls) in all of the preparations and p-coumaric acid (mostly
      trans) (0-106ug/g cell walls) in all except one of them. Ferulic acid ester
      linked to primary cell walls has previously been found in angiosperms: in the
      commelinoid monocotyledons and in the dicotyledon order Caryophyllales, both
      monophyletic groups. From the present results, we postulate that the extant
      classes of gymnosperms are monophyletic and no class is sister to the
      angiosperms.

PMID- 10913849
TI  - UV-guided screening of benzodiazepine producing species in Penicillium.
AB  - The benzodiazepine sclerotigenin (auranthine B) recently described as a
      metabolite of Penicillium sclerotigenum, has been isolated as the major
      metabolite from an isolate of P. commune. The structure of sclerotigenin was
      established by a single-crystal X-ray diffraction study and by NMR spectroscopy.
      UV-guided screening for benzodiazepine production by other penicillia revealed
      that sclerotigenin was also produced by isolates of P. clavigerum, P. lanosum, P.
      melanoconidium, P. sclerotigenum and P. verrucosum. Sclerotigenin was detected
      both intra- and extracellularly. Apparently, P. aurantiogriseum is the only
      auranthine producing species in genus Penicillium.

PMID- 10913851
TI  - Short-chain carboxylic acids from the anal glands of the binturong, Arctictis
      binturong (Viverridae, Mammalia).

PMID- 10913850
TI  - Anthocyanins in flowers of genus Rosa, sections Cinnamomeae (=Rosa), Chinenses,
      Gallicanae and some modern garden roses.
AB  - Forty-four taxa of three sections (Cinnamomeae (=Rosa) 26, Chinenses 8 and
      Gallicanae 10) and eight modern garden roses in the genus Rosa were surveyed for
      their floral anthocyanins. Eleven anthocyanins: 3-glucosides and 3,5-diglucosides
      of cyanidin (Cy), pelargonidin (Pg) and peonidin (Pn), 3-rutinosides and 3-rho
      coumaroylglucoside-5-glucosides of Cy and Pn, and Cy 3-sophoroside, were isolated
      from flowers of these taxa and identified by chemical and spectroscopic
      techniques. Four anthocyanins: Cy 3-rutinoside, Pn 3-rutinoside, Pn 3-rho
      coumaroylglucoside-5-glucoside and Cy 3-sophoroside were found for the first time
      in Rosa flowers.Investigated sections of wild roses showed characteristic
      distribution of anthocyanins. Cy 3,5-diglucoside was the dominant anthocyanin
      detected in all three sections, but accumulation of Pn 3,5-diglucoside
      distinguished sections Cinnamomeae from other sections, and the occurrence of Cy
      3-glucoside separates section Chinenses from others.Cy 3-sophoroside was detected
      in large amount in some taxa of section Cinnamomeae: e.g., R. moyesii and its
      related cultivars, and R. rugosa cv. Salmon Pink. The acylated Cy glycoside was
      found in all sections and also in some modern garden roses, while the acylated Pn
      glycoside was detected in the section Cinnamomeae, but not in sections Chinenses
      and Gallicanae. According to anthocyanin distribution patterns, eight groups were
      classified chemotaxonomically in genus Rosa.

PMID- 10913852
TI  - Halleridone and Hallerone from Phyla nodiflora as taxonomic markers.

PMID- 10913853
TI  - Constituents of Valeriana glechomifolia Meyer.

PMID- 10913854
TI  - Stigmast-4-ene-3,6-dione an unusual phytotoxic sterone from the roots of Echium
      vulgare L.

PMID- 10913855
TI  - The flavonoids of four Pistacia species in Egypt.

PMID- 10913856
TI  - The flavonoid chemosystematics of Egyptian Verbena species.

PMID- 10913857
TI  - Antibody engineering and its applications in tumor targeting and intracellular
      immunization.
AB  - During the last decade, recombinant antibody engineering has emerged as one of
      the most promising approaches for the design, selection and production of
      molecules for basic research, medicine and the pharmaceutical industry. This
      MiniReview describes the major findings that have led to the development of this
      powerful technique, with an emphasis on the use of Escherichia coli and
      filamentous phage as a tool allowing powerful selection procedures from large
      libraries as well as the use of intracellular expression of antibody fragments as
      a new class of neutralizing molecules with a potential use in therapy. The future
      of these rapidly evolving technologies is discussed.

PMID- 10913858
TI  - Cellular stress responses oscillate in synchronization with the ultradian
      oscillation of energy metabolism in the yeast Saccharomyces cerevisiae.
AB  - We investigated whether cellular responses to various stress conditions are
      regulated in synchronization with the ultradian rhythm of respiratory
      fermentative metabolism which is coupled to the cell cycle rhythm in continuous
      cultures of the yeast Saccharomyces cerevisiae. The cellular resistance to heat
      oscillated with a peak at the late respiro-fermentative phase, which
      approximately corresponds to the unbudding period of the cell cycle. Cellular
      resistance to H(2)O(2) and that to the superoxide-generating agent menadione
      oscillated in the same phase as that of heat resistance. The resistance to
      cadmium and that to 1-chloro-2,4-dinitrobenzene, an uncoupler of energy
      metabolism in mitochondria, both oscillated with a peak advanced by about 80
      degrees relative to that of heat resistance, approximately covering the respiro
      fermentative phase. Thus, cellular resistance to various stresses in S.
      cerevisiae oscillated in synchronization with the metabolic oscillation in the
      continuous culture.

PMID- 10913859
TI  - Identification of type 4 fimbriae in Actinobacillus pleuropneumoniae.
AB  - Type 4 fimbriae have been identified on the cell surface of Actinobacillus
      pleuropneumoniae by electron microscopy and N-terminal sequencing analysis. A.
      pleuropneumoniae type 4 fimbrial subunit protein, purified from cell cultures and
      from outer membrane preparations, reacted with polyclonal antibody raised against
      type 4 fimbriae of Moraxella bovis on Western blots. N-terminal sequence analysis
      of the purified 17 kDa type 4 fimbrial subunit protein, named ApfA, revealed the
      first 12 amino acids to be identical to those of other type 4 fimbrial subunit
      proteins.

PMID- 10913860
TI  - A variation of the amplified-fragment length polymorphism (AFLP) technique using
      three restriction endonucleases, and assessment of the enzyme combination BglII
      MfeI for AFLP analysis of Salmonella enterica subsp. enterica isolates.
AB  - We have performed amplified-fragment length polymorphism (AFLP) fingerprinting on
      a collection of Salmonella enterica subsp. enterica serovar typhimurium strains
      with a restriction endonuclease combination (BglII and MfeI) that has previously
      been used successfully for typing Campylobacter jejuni isolates with high
      resolution. Additionally, a variation of the AFLP assay in which two rare cutting
      restriction enzymes (XbaI and BsrGI) in combination with the frequent cutter
      (HinP1I) was examined. The BglII and MfeI enzyme combination offered low
      resolution for genotyping Salmonella typhimurium isolates and is not recommended
      for this common serovar. The three-enzyme combination gave a higher
      discrimination, and is thus a new alternate way of performing AFLP fingerprinting
      of S. typhimurium.

PMID- 10913861
TI  - Properties of a bacterium which degrades solid poly(tetramethylene succinate)-co
      adipate, a biodegradable plastic.
AB  - Various microorganisms were screened for their ability to degrade
      poly(tetramethylene succinate)-co-(tetramethylene adipate) (PBSA). Strain BS-3,
      which was newly isolated from a soil sample, was selected as the best strain.
      From taxonomical studies, the strain was tentatively ascribed to belong to the
      genus Acidovorax, most probably to the species A. delafieldii. Strain BS-3 could
      degrade both solid and emulsified PBSA, and also emulsified poly(tetramethylene
      succinate). During the degradation, a lipase activity was observed in the culture
      broth. This lipase activity was induced more strongly by PBSA than by tributyrin
      or triolein which are typical substrates of lipase. These observations strongly
      suggest that this lipase was involved in the PBSA biodegradation in strain BS-3.

PMID- 10913863
TI  - High efficiency separation of microbial aggregates using capillary
      electrophoresis.
AB  - Recent advances in the technique of capillary electrophoresis have demonstrated
      fast, highly efficient separation of mixtures of intact microbes. This paper
      describes the application of this technique for the separation of microbial
      aggregates of Micrococcus luteus, Saccharomyces cerevisiae, or Alcaligenes
      faecalis. The aggregates of these microbes were resolved into several highly
      efficient peaks with analysis times under 10 min and efficiencies approaching
      1000000 plates m(-1) in some cases. A reproducible relationship was found between
      the electrophoretic mobility and the aggregation number or size of the cluster
      under a given set of experimental conditions. Often, cellular aggregation was
      reversible with brief immersion in an ultrasound bath. This reversibility was
      confirmed by visual microscopy and electrophoretic data.

PMID- 10913862
TI  - Identification and transcriptional characterization of the gene encoding the
      stress-response sigma factor sigma(H) in streptomyces coelicolor A3(2).
AB  - We cloned a new gene, sigH, encoding an alternative sigma factor in Streptomyces
      coelicolor A3(2). The deduced protein of 354 amino acids with an M(r) of 39486
      showed greatest similarity to the sporulation sigma factor (sigma(F)) of S.
      coelicolor, general stress-response sigma(B) of Bacillus subtilis, and stationary
      phase stress-response sigma(F) of Mycobacterium tuberculosis. Sequence analysis
      of the upstream region revealed an ORF encoding a protein (UshX) similar to
      several anti-sigma factors, and short ORF (UshY) containing zinc-finger DNA
      binding motif. Transcriptional analysis revealed that all three genes are located
      on the same polycistronic transcript in order ushY, ushX, and sigH. Expression of
      the operon was directed by four promoters differentially expressed in the course
      of differentiation. The first (P1) constitutive promoter was located upstream of
      ushY. The other three promoters (P2, P3, and P4) were located upstream of ushX,
      and were differentially induced after various stress conditions. The magnitude of
      the induction was greatest after osmotic stress and heat shock.

PMID- 10913864
TI  - Cloning and characterization of PKC-homologous genes in the truffle species Tuber
      borchii and Tuber magnatum.
AB  - The protein kinases C (PKCs) define a growing family of ubiquitous signal
      transducting serine/threonine kinases that control ion conductance channels,
      release of hormones and cell growth and proliferation. Degenerated
      oligonucleotides were used as primers for polymerase chain reactions to amplify
      PKC-related sequences from the white truffle species Tuber magnatum and Tuber
      borchii. The deduced amino acid sequences of cloned sequences reveal domains
      homologous to the regulatory and kinase domains of PKC-related proteins, but lack
      typical Ca(2+)-binding domain and therefore should be classified as nPKCs. Both
      contain a large extended N-terminus which is found exclusively in fungi PKCs.
      Phylogenetic analysis of the kinase domain demonstrates high homology with known
      filamentous fungi isoenzymes.

PMID- 10913865
TI  - Hemin-dependent growth and hemin binding of Bartonella henselae.
AB  - Bartonella henselae causes cat-scratch disease and bacillary angiomatosis
      peliosis. The bacteria reside in erythrocytes of asymptomatic cats, which
      represent the natural reservoir for this pathogen. B. henselae is usually grown
      on blood-enriched media. Growth experiments on Brucella medium without blood
      demonstrated that heme compounds are essential for the growth of B. henselae and
      can completely substitute the addition of blood components. The heme precursor
      protoporphyrin IX alone, or in combination with FeCl(2) or FeCl(3), as well as
      transferrin or lactoferrin did not support growth, indicating that B. henselae
      cannot synthesize heme itself. Hemin supported growth even when free iron was
      chelated, indicating that hemin is also used as an iron source. Binding assays
      showed that hemin starvation increased the binding capacity of B. henselae for
      hemin, providing evidence that the bacteria carry a specific hemin uptake system,
      which might be regulated by hemin.

PMID- 10913866
TI  - ITS1 region of the nuclear ribosomal DNA of the mycoparasite Pythium periplocum,
      its taxonomy, and its comparison with related species.
AB  - Pythium periplocum Drechsler was isolated from some soil samples taken in the
      botanical garden of Tenerife, Canary Islands. This fungus has been found to be an
      aggressive mycoparasite of Botrytis cinerea. It is unique amongst the members of
      the genus Pythium because of the character combination of inflated filamentous
      type of sporangia and ornamented oogonia. The taxonomic description of this
      fungus and its comparison with related species, together with the polymerase
      chain reaction of the internal transcribed spacer of its nuclear ribosomal DNA,
      are discussed in this article.

PMID- 10913867
TI  - Characterization of methanotrophic bacteria on the basis of intact phospholipid
      profiles.
AB  - The intact phospholipid profiles (IPPs) of seven species of methanotrophs from
      all three physiological groups, type I, II and X, were determined using liquid
      chromatography/electrospray ionization/mass spectrometry. In these methanotrophs,
      two major classes of phospholipids were found, phosphatidylglycerol (PG) and
      phosphatidylethanolamine (PE) as well as its derivatives
      phosphatidylmethylethanolamine (PME) and phosphatidyldimethylethanolamine (PDME).
      Specifically, the type I methanotrophs, Methylomonas methanica, Methylomonas
      rubra and Methylomicrobium album BG8 were characterized by PE and PG
      phospholipids with predominantly C16:1 fatty acids. The type II methanotrophs,
      Methylosinus trichosporium OB3b and CSC1 were characterized by phospholipids of
      PG, PME and PDME with predominantly C18:1 fatty acids. Methylococcus capsulatus
      Bath, a representative of type X methanotrophs, contained mostly PE (89% of the
      total phospholipids). Finally, the IPPs of a recently isolated acidophilic
      methanotroph, Methylocella palustris, showed it had a preponderance of PME
      phospholipids with 18:1 fatty acids (94% of total). Principal component analysis
      showed these methanotrophs could be clearly distinguished based on phospholipid
      profiles. Results from this study suggest that IPP can be very useful in
      bacterial chemotaxonomy.

PMID- 10913868
TI  - Cloning and characterisation of a chitin synthase gene cDNA from the cultivated
      mushroom Agaricus bisporus and its expression during morphogenesis.
AB  - Full-length cDNA of a chitin synthase gene (chs1) was cloned from Agaricus
      bisporus by screening a cDNA library with a PCR amplified fragment of the chitin
      synthase gene. The chs1 contains an open reading frame of 2727 bp encoding a
      polypeptide of 909 amino acids and deduced molecular mass 102.3 kDa and pI 8.23.
      The central region of chs1 showed strong homology to other fungal chitin synthase
      genes with seven conserved domains. It belongs to the chitin synthase class III,
      analogous to chsB from Aspergillus nidulans, chsC and chsG from A. fumigatus and
      chs-1 from Neurospora crassa. It appears to be fruit body induced as the
      transcripts were higher in the developing mushroom compared to any mycelial
      stage.

PMID- 10913869
TI  - A cadmium resistance plasmid, pXU5, in Staphylococcus aureus, strain ATCC25923.
AB  - A 25.9-kb plasmid, pXU5, encoding high level cadmium resistance was isolated from
      Staphylococcus aureus strain ATCC25923. A labelled cadA probe from plasmid pI258
      hybridised to a 2.3-kb EcoRI fragment of pXU5. pXU5 was incompatible with an S.
      aureus incompatibility group 1 plasmid.

PMID- 10913870
TI  - Direct profiling of the yeast dynamics in wine fermentations.
AB  - We present a method to directly characterize the yeast diversity present in wine
      fermentations by employing denaturing gradient gel electrophoresis (DGGE) of
      polymerase chain reaction (PCR)-amplified 26S ribosomal RNA (rRNA) genes. PCR
      DGGE of a portion of the 26S rRNA gene was shown to distinguish most yeast genera
      associated with the production of wine. With this method the microbial dynamics
      in several model wine fermentations were profiled. PCR-DGGE provided a
      qualitative assessment of the yeast diversity in these fermentations accurately
      identifying populations as low as 1000 cells ml(-1). PCR-DGGE represents an
      attractive alternative to traditional plating schemes for analysis of the
      microbial successions inherent in the fermentation of wine.

PMID- 10913871
TI  - Shifts in membrane fatty acid profiles associated with acid adaptation of
      Streptococcus mutans.
AB  - Cells of Streptococcus mutans UA159 physiologically adapted to acidification
      during growth at pH 5 in glucose-limited chemostat cultures were enriched in mono
      unsaturated and longer chain fatty acids compared with unadapted cells grown
      under the same conditions but at pH 7. Ratios of unsaturated to saturated fatty
      acids in the cells were, respectively, 1.2 and 0.3. Cyclopropane fatty acids were
      not detected. Streptococcus sobrinus 6715, which is known to have minimal acid
      adaptive capacity, showed only minimal change in membrane fatty acids.

PMID- 10913872
TI  - Hopanoids are formed during transition from substrate to aerial hyphae in
      Streptomyces coelicolor A3(2).
AB  - Streptomyces coelicolor A3(2) contains a cluster of putative isoprenoid and
      hopanoid biosynthetic genes. The strain does not produce the pentacyclic
      hopanoids in liquid culture but produces them on solid medium when sporulating.
      Mutants defective in the formation of aerial mycelium and spores (bld), with the
      exception of bldB, do not synthesize hopanoids, whereas mutants, which form
      aerial mycelium but no spores (whi), do. The membrane condensing hopanoids
      possibly may alleviate stress in aerial mycelium by diminishing water
      permeability across the membrane.

PMID- 10913873
TI  - Identification of Colletotrichum species responsible for anthracnose of
      strawberry based on the internal transcribed spacers of the ribosomal region.
AB  - In recent years, different molecular techniques have led to an important progress
      in the characterisation of Colletotrichum species, but there are no available
      methods which permit the easy identification of Colletotrichum strains and their
      assignation to classical species. In the present work, the restriction patterns
      generated from the region spanning the internal transcribed spacers (ITS1 and
      ITS2) and the 5.8S rRNA gene, were used to identify a total of 80 strains of
      Colletotrichum, the majority of them isolated from strawberry. One of the most
      interesting results derived from this study was the easy and reliable
      distinction, using the endonuclease MvnI, between Colletotrichum fragariae and
      Colletotrichum gloeosporoides, both responsible of anthracnose on strawberry and
      phenotypically indistinguishable. Moreover, we propose the restriction fragments
      generated by the endonucleases MvnI, PvuII and ScrFI as a rapid method to
      differentiate species of the Colletotrichum genus.

PMID- 10913874
TI  - Rapid isolation and identification of staphylococcal exoproteins by reverse phase
      capillary high performance liquid chromatography-electrospray ionization mass
      spectrometry.
AB  - The isolation of staphylococcal extracellular toxins and enzymes (exoproteins)
      usually requires time-consuming purification steps such as repeated
      chromatographic separations and isoelectric focusing. We performed rapid
      isolation, quantification and identification of staphylococcal exoproteins by
      reverse phase capillary high performance liquid chromatography-electrospray
      ionization mass spectrometry (LC-ESI/MS) followed by the determination of N
      terminal amino acid sequences of separated peaks. We identified two novel
      exoproteins as well as previously reported antigens ORF-1 and ORF-2, glutamyl
      endopeptidase in Staphylococcus aureus NCTC8325 and protein A, staphylococcal
      enterotoxin C3 (SEC3), toxic shock syndrome toxin-1 (TSST-1) and alpha-toxin in a
      clinical isolate methicillin-resistant S. aureus (MRSA) 3543. MRSA3543 secreted
      5.33 and 1.45 microg of SEC3 and TSST-1 per 20 microg total exoproteins ml(-1),
      respectively. The capillary LC treatment of the exoprotein fraction separated at
      least 12 peaks, indicating its high-resolution power. We found that when a
      protein was once determined by its N-terminal sequence, its mass spectrum and the
      obtained molecular mass was applicable for the assignment of the protein.

PMID- 10913875
TI  - Clostridium perfringens epsilon toxin causes excessive release of glutamate in
      the mouse hippocampus.
AB  - The mechanism of neurotoxicity of Clostridium perfringens epsilon toxin to the
      mouse brain was investigated. Intravenous injection in mice with the toxin caused
      seizure and excited hippocampal neurons. Microdialysis revealed that epsilon
      toxin induced excessive glutamate release in the hippocampus. Both the seizure
      and glutamate release were attenuated by prior injection with riluzole, an
      inhibitor of pre-synaptic glutamate release, suggesting that this toxin enhances
      glutamate efflux, leading to seizure and hippocampal neuronal damage.

PMID- 10913876
TI  - Candida glabrata displays pseudohyphal growth.
AB  - The ability to undergo morphological change has been reported as an advantageous
      trait in fungal pathogenesis. Here we demonstrate that Candida glabrata ATCC2001,
      like diploid Saccharomyces cerevisiae strains, forms elongated chains of
      pseudohyphal cells on solid nitrogen starvation media (SLAD). Constrictions were
      apparent between adjoining cells; no parallel-sided hyphae were seen and
      pseudohyphae invaded the agar. When SLAD was supplemented with ammonium sulfate
      both C. glabrata and diploid S. cerevisiae strains lost their ability to undergo
      pseudohyphal growth. However, on this media C. glabrata yeast cells invaded the
      agar in a similar fashion to the invasive growth mode exhibited by haploid
      strains of S. cerevisiae cultured on rich media such as YPD. C. glabrata was not
      capable of invading YPD demonstrating that the process of filamentation is
      distinct in these two fungi. To our knowledge this is the first report to
      demonstrate that C. glabrata can undergo morphological change and grow as an
      invasive filamentous organism.

PMID- 10913877
TI  - The nine C-terminal amino acids of the major capsid protein of the human
      papillomavirus type 16 are essential for DNA binding and gene transfer capacity.
AB  - Four C-terminal deletion mutants of the human papillomavirus 16 L1 protein were
      expressed in the baculovirus expression system. They consist of the deletion of
      amino acids 497-505, 477-505, 403-505 and 302-505 (delta C9, delta C31, delta
      C103 and delta C204 respectively). Only two of the C-terminally deleted proteins,
      delta C9 and delta C31, retained the ability to form virus-like particles (VLPs)
      resembling those obtained with the full length L1 protein. Analysis of deleted L1
      proteins and corresponding VLPs indicated that the C-terminus was necessary both
      for DNA binding and DNA packaging. These results were corroborated by the loss of
      the gene transfer capacities of C-terminal deleted VLPs.

PMID- 10913878
TI  - Upregulation of glial cell line-derived neurotrophic factor (GDNF) in the rat
      cochlea following noise.
AB  - There are endogenous intracellular mechanisms that provide cells with protection
      from stress, as well as repair from damage. These pathways often involve stress
      proteins and neurotrophic factors. The present study used Western blot analysis
      to examine changes in glial cell line-derived neurotrophic factor (GDNF)
      following noise overstimulation. A noise exposure was utilized which causes a
      temporary threshold shift and has been previously shown to upregulate heat shock
      protein 72 in the rat cochlea. This noise exposure also provides protection from
      a second noise exposure that would otherwise cause a permanent threshold shift.
      Experimental animals were assessed 2, 4, 8 and 12 h after cessation of noise
      exposure. Control animals received the same treatment except for the noise
      exposure and were assessed at the 8 h time point. A moderate expression of GDNF
      was observed in the normal cochlea. No significant change in GDNF levels was
      observed at 2 or 4 h following noise overstimulation. However, a significant
      increase was found at 8 h. At 12 h following noise overstimulation, GDNF levels
      were no longer significantly elevated from normal. These results suggest that
      GDNF is involved in the endogenous stress response in the cochlea and are
      consistent with the protection that exogenously applied GDNF has been shown to
      provide.

PMID- 10913879
TI  - Voltage-dependent K(+) currents in spiral prominence epithelial cells of rat
      cochlea.
AB  - It has been suggested that spiral prominence is associated with ion transport,
      but the characterization of ion channels has not been explored so far. We studied
      the electrical properties and ion conductances of the spiral prominence
      epithelial cells (SPECs), which are epithelial cells covering the luminal side of
      spiral prominence, in the upper turn of neonatal rat cochlea using a whole-cell
      variant patch clamp technique. The cell capacitance was 16.3+/-2.1 pF (n=33) and
      the resting membrane potential was -68. 9+/-2.5 mV (n=14) in perilymph-like bath
      solution. It was found that those SPECs possess a large voltage-activated,
      outwardly rectifying K(+) current and a small inwardly rectifying K(+) current.
      The outward K(+) current was activated by depolarizing pulses more positive than 
      30 mV, and sensitive to tetraethylammonium chloride (20 mM), 4-aminopyridine (10
      mM), but not to Ba(2+) (0.5 mM). Tail current analysis revealed that it was
      primarily K(+)-selective. The time course of activation was well fitted by an
      exponential function raised to second power. The small inwardly rectifying K(+)
      current was sensitive to Ba(2+) (0.5 mM), and the Ba(2+)-sensitive current was
      K(+)-selective. In cell-attached or inside-out patch recordings, no discernible
      K(+) channel currents were found in the apical membrane of SPECs. Based on these
      results, we conclude that SPECs have two types of voltage-dependent K(+)
      currents, which are most likely located in the basolateral membrane.

PMID- 10913880
TI  - A role for chloride in the hyperpolarizing effect of acetylcholine in isolated
      frog vestibular hair cells.
AB  - Acetylcholine (ACh) is the dominant transmitter released from inner ear efferent
      neurons. In frog vestibular organs, these efferent neurons synapse exclusively
      with type II hair cells. Hair cells isolated from the frog saccule hyperpolarize
      following the application of 50 microM ACh, thereby demonstrating the presence of
      an ACh receptor. A role for Cl(-) in the response of hair cell-bearing organs to
      efferent nerve activation or ACh application was suggested some years ago.
      Perfusion with solutions in which most of the Cl(-) was replaced by large
      impermeant anions decreased the cholinergic inhibition of afferent firing in the
      cat and turtle cochleas, and frog semicircular canal. Our previous work in the
      intact organ demonstrated that substitution of large impermeant anions for Cl(-)
      or use of Cl(-) channel blockers reduced the effect of ACh on saccular afferent
      firing. Using the perforated-patch clamping technique, replacement of Cl(-) by
      methanesulfonate, iodide, nitrate, or thiocyanate attenuated the hyperpolarizing
      response to ACh in hair cells isolated from the frog saccule. The chloride
      channel blockers picrotoxin and 4,4'-dinitrostilbene-2,2'-disulfonic acid were
      also tested and found to inhibit the ACh response. Thus, the present work
      demonstrates that the effects of Cl(-) substitutions or Cl(-) channel blockers on
      the ACh response in the intact saccule can be explained completely by effects on
      the hair cell. Evidence is also presented for the presence of the messenger RNA
      for a calcium-dependent chloride channel in all hair cells but especially
      saccular hair cells. This channel may be involved in the response to ACh. The
      precise role for chloride in this response, whether as a distinct ion current, as
      a transported ion, or as a permissive ion for other components, is discussed.

PMID- 10913881
TI  - Glutathione limits noise-induced hearing loss.
AB  - The generation of reactive oxygen species (ROS) is thought to be part of the
      mechanism underlying noise-induced hearing loss (NIHL). Glutathione (GSH) is an
      important cellular antioxidant that limits cell damage by ROS. In this study, we
      investigated the effectiveness of a GSH supplement to protect GSH-deficient
      animals from NIHL. Pigmented guinea pigs were exposed to a 4 kHz octave band
      noise, 115 dB SPL, for 5 h. Group 1 had a normal diet, while groups 2, 3 and 4
      were fed a 7% low protein diet (leading to lowered tissue levels of GSH) for 10
      days prior to noise exposure. One hour before, immediately after and 5 h after
      noise exposure, subjects received either an intraperitoneal injection of 5 ml/kg
      body weight of 0.9% NaCl (groups 1 and 2), 0.4 M glutathione monoethyl ester
      (GSHE; group 3) or 0.8 M GSHE (group 4). Auditory thresholds were measured by
      evoked brain stem response at 2, 4, 8, 12, 16 and 20 kHz before and after noise
      exposure. Ten days post exposure, group 1 showed noise-induced threshold shifts
      of approximately 20 dB at 2, 16 and 20 kHz and 35 to 40 dB at other frequencies.
      Threshold shifts in group 2 were significantly greater than baseline at 2, 4, 16
      and 20 kHz. GSHE supplementation in a dose-dependent fashion attenuated the
      threshold shifts in the low protein diet animals. Hair cell loss, as evaluated
      with cytocochleograms, was consistent with the auditory-evoked brainstem response
      results. Group 2 exhibited significantly more hair cell loss than any of the
      other groups; hair cell loss in group 3 was similar to that seen in group 1;
      group 4 showed less loss than group 1. These results indicate that GSH is a
      significant factor in limiting noise-induced cochlear damage. This is compatible
      with the notion that ROS generation plays a role in NIHL and that antioxidant
      treatment may be an effective prophylactic intervention.

PMID- 10913882
TI  - Immunological evidence that anemone repair proteins include replacement linkages.
AB  - In response to damage to hair bundles caused by exposure to calcium free buffers,
      sea anemones secrete large protein complexes named 'repair proteins' that rapidly
      restore structural integrity and function to hair bundles. A specific
      chromatographic fraction of the repair protein mixture, named 'fraction beta',
      has biological activity comparable to the complete repair protein mixture (Watson
      et al., 1998, Hear. Res. 115, 119-128). In this study, we find that polyclonal
      antibodies raised against deglycosylated fraction beta specifically bind fraction
      beta on Western blots. Anti-fraction beta delays the normal recovery of vibration
      sensitivity in experimental animals (i.e., those with hair bundles damaged by
      calcium free buffers). Moreover, anti-fraction beta disrupts vibration
      sensitivity in control animals (i.e., those with healthy hair bundles).
      Experimentally damaged hair bundles subsequently exposed to repair protein and
      then processed for immunoelectron microscopy show labeled linkages
      interconnecting stereocilia of the hair bundle. Immunofluorescence microscopy
      confirms strong labeling of hair bundles treated with repair proteins and only
      weak labeling of tips of hair bundles from control animals. Immunofluorescence
      microscopy indicates stores of repair proteins in gland cells of the body column
      in control animals and in gland cells of the mouth in experimental animals.
      Repair biological activity is confirmed in column purified homogenates of these
      tissues. Apparently repair proteins are delivered to damaged hair bundles in
      mucus carried by beating cilia.

PMID- 10913883
TI  - Optimal L(1)-L(2) primary tone level separation remains independent of test
      frequency in humans.
AB  - Previous studies described a systematic asymmetry of the level of the 2f(1)-f(2)
      distortion product otoacoustic emission (DP) in the space of the primary tones
      levels L(1) and L(2) in normal-hearing humans. Optimal primary tone level
      separations L(1)-L(2), which result in maximum DP levels, were close to L(1)=L(2)
      at high levels, but continuously increased with decreasing stimulus level towards
      L(1)>L(2) (Gaskill and Brown, 1990, J. Acoust. Soc. Am. 88, 821-839). At these
      optimal L(1)-L(2), however, not only DP levels in normal hearing were maximal,
      but also trauma-induced DP reductions. A linear equation that approximates
      optimal L(1)-L(2) level separations thus was suggested to be optimum for use in
      clinical applications (Whitehead et al., 1995, J. Acoust. Soc. Am. 97, 2359
      2377). It was the aim of this study to extend the generality of optimal L(1)-L(2)
      separations to the typical human test frequency range for f(2) frequencies
      between 1 and 8 kHz. DPs were measured in 22 normal-hearing human ears at 61
      primary tone level combinations, with L(2) between 5 and 65 dB SPL and L(1)
      between 30 and 70 dB SPL (f(2)/f(1)=1.2). It was found that the systematic
      dependence of the maximum DP level on the L(1)-L(2) separation is independent on
      frequency. Optimal L(1)-L(2) level separations may well be approximated by a
      linear equation L(1)=a L(2)+(1-a) b (after Whitehead et al., 1995) with
      parameters a=0.4 and b=70 dB SPL at f(2) frequencies between 1 and 8 kHz and L(2)
      levels between 20 and 65 dB SPL. Below L(2)=20 dB SPL, the optimal L(1) was found
      to be almost constant. Following previous notions (Gaskill and Brown, 1990), an
      analysis of basilar membrane response data in experimental animals (after Ruggero
      and Rich, 1991, Hear. Res. 51, 215-230) is further presented that relates optimal
      L(1)-L(2) separations to frequency-selective compression of the basilar membrane.
      Based on the assumption that optimal conditions for the DP generation are equal
      primary tone responses at the f(2) place, a linear increase of the optimal L(1)
      L(2) level separation is graphically demonstrated, similar to our results in
      human ears.

PMID- 10913884
TI  - Reduction in excitability of the auditory nerve following electrical stimulation
      at high stimulus rates: V. Effects of electrode surface area.
AB  - High rate intracochlear electrical stimulation at high intensities can induce
      significant reductions in the excitability of the auditory nerve as measured by a
      decrement in the amplitude of the electrically evoked auditory brainstem response
      (EABR). Such changes are primarily associated with stimulus induced neuronal
      activity, although direct current (DC) can also contribute. We examined the
      extent of stimulus induced change in auditory nerve excitability using large
      surface area platinum electrodes ('high-Q' electrodes). These electrodes have a
      surface area approximately 70 times greater than standard Pt electrodes of the
      same geometric area, resulting in lower DC and charge density (charge/electrode
      surface area) for a common stimulus. Guinea pigs were bilaterally implanted with
      either high-Q or standard Pt electrodes, and unilaterally stimulated for 2 h
      using stimulus intensities of 12 dB or 20-30 dB above EABR threshold (0.34
      microC/phase) at stimulus rates of 200, 400, or 1000 pulses per second (pps).
      EABRs were recorded before and following the acute stimulation. While there were
      significant reductions in EABR amplitudes and elevated EABR thresholds following
      stimulation at 12 dB above threshold using 400 and 1000 pps delivered to standard
      Pt electrodes, there were fewer or no significant changes in the post-stimulus
      EABR amplitude and threshold using high-Q electrodes under equivalent stimulus
      conditions. At a higher stimulus intensity (20-30 dB above EABR threshold), no
      reduction in EABR amplitude was observed at 200 pps for both stimulating
      electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. There
      was significantly greater EABR recovery following stimulation using high-Q
      electrodes compared with standard Pt electrodes at 400 (P<0.05) and 1000 pps
      (P<0.05). These data indicate that large surface area electrodes can
      significantly reduce stimulus induced changes in auditory nerve excitability, and
      may therefore have important clinical application.

PMID- 10913886
TI  - Bone conduction experiments in humans - a fluid pathway from bone to ear.
AB  - Animal experiments in this laboratory have led to the suggestion that a major
      pathway in bone conduction stimulation to the inner ear is via the skull contents
      (brain and CSF). This hypothesis was now tested in humans. Auditory nerve
      brainstem evoked responses could be recorded in neonates to bone conduction
      stimulation over the fontanelle and audiometric responses were obtained in
      neurosurgical patients with the bone vibrator on the skin over a craniotomy.
      There were no differences in threshold between these responses and those obtained
      to bone conduction stimulation over skull bone in the same subjects. Audiometric
      thresholds in response to bone vibrator stimulation of the eye (a 'natural
      craniotomy') were no different from those to bone stimulation delivered to
      several sites on the head. Thus there is no need to vibrate bone in order to
      obtain 'bone conduction' responses. Bone vibrator thresholds to stimulation at
      the head region with thinnest bone (temporal) were better than those to
      stimulation at the forehead region which has much thicker bone, implying that the
      vibrations penetrate the skull at the site of the vibrator. In addition, the
      magnitude of vibration (acceleration) measured at various sites around the head
      in response to bone vibrator stimulation at a fixed point on the forehead
      generally decreased with distance from the point of vibration. Therefore it seems
      that the vibrations produced by a bone vibrator at a point on the head are also
      able to penetrate the skull, setting up audio-frequency pressures in the CSF
      which spread by fluid communications to the inner ear fluids, exciting the ear.

PMID- 10913885
TI  - Bone conduction experiments in animals - evidence for a non-osseous mechanism.
AB  - Bone conducted stimuli are used to differentiate between conductive and sensori
      neural hearing loss. It has been thought that the main route for the transfer of
      vibratory energy from the point of application of the bone vibrator on the skull
      to the inner ear is completely osseous. An additional mechanism may play a
      prominent role. In rats, a bone vibrator was applied to the skull and also
      directly on the brain, after removing bone (a craniotomy), exposing the brain.
      Auditory nerve-brainstem evoked response (ABR) could be elicited not only with
      the vibrator on bone, but also with the vibrator directly on the brain. Similar
      results were obtained in guinea-pigs and fat sand rats. Noise masked this ABR.
      Extensive removal of skull bone did not alter the ABR to bone-conducted stimuli
      delivered to the exposed brain. Experimental elimination of the ossicular chain
      inertial mechanism and of the occlusion effect did not greatly alter the bone
      conduction response. A reduction in the fluid volume of the cranial cavity
      induced threshold elevations of the bone conducted ABR but not of the air
      conducted ABR. These findings can be interpreted as evidence that the 'classical'
      bone conduction mechanisms should be modified to include a major pathway for
      cochlear excitation which is non-osseous: when a bone vibrator is applied to the
      skull, the bone vibrations may induce audio-frequency sound pressures in the
      skull contents (brain and cerebro-spinal fluid) which are then communicated by
      fluid channels to the fluids of the inner ear.

PMID- 10913887
TI  - Nonlinear temporal interactions in click-evoked otoacoustic emissions. I. Assumed
      model and polarity-symmetry.
AB  - Click-evoked otoacoustic emissions (CEOAEs) are reduced in amplitude by the
      presentation of 'suppressor' clicks that either closely lead or follow the
      stimulus ('test') clicks. This suppression of the response represents nonlinear
      temporal interactions between the test and suppressor clicks and/or the CEOAEs
      they evoke. There are some discrepancies amongst previous reports of the
      phenomenon, and the underlying mechanisms are not understood. In particular, it
      is unclear whether the suppression reported simply reflects the compressive
      nonlinearity of the CEOAE input-output (I-O) function. This paper presents a
      simple model of the nonlinear interactions between CEOAEs evoked by two closely
      spaced clicks. The model shows that suppression as reported may be entirely
      derived from CEOAE I-O nonlinearity, in combination with the extended duration of
      the cochlear responses to click stimuli. It is also shown experimentally that
      suppression is insensitive to the polarities of test and suppressor clicks, which
      is consistent with the model based on I-O nonlinearity. A companion paper
      (Kapadia and Lutman, Hear. Res. 146 (2000)) presents experimental findings from a
      detailed parametric study of nonlinear temporal interactions in CEOAEs in human
      subjects with normal hearing. The findings are compared with the pattern of
      results generated by the above model, in order to assess the role of I-O
      nonlinearity in these nonlinear interactions.

PMID- 10913888
TI  - Nonlinear temporal interactions in click-evoked otoacoustic emissions. II.
      Experimental data.
AB  - Click-evoked otoacoustic emissions (CEOAEs) are reduced in amplitude by the
      presentation of 'suppressor' clicks that either closely lead or follow the
      stimulus ('test') clicks. A model described in a companion paper (Kapadia and
      Lutman, Hear. Res. 146 (2000) 89-100) shows that such nonlinear temporal
      interactions, as previously reported, may be explained in terms of the
      compressive non-linearity of the CEOAE input-output (I-O) function. This paper
      presents the results of a detailed parametric investigation into such nonlinear
      interactions, studied in 12 normal adult ears over a wide range of test and
      suppressor click levels and inter-click intervals. The results differ from those
      generated by the model in a number of respects. Principally, maximum suppression
      is generally obtained for suppressors presented in advance of test clicks, rather
      than co-incident with the test clicks. The amount of advance depends
      systematically on the two click levels. The measured suppression can also exceed
      the theoretical maximum allowed by the model. It is concluded that the nonlinear
      temporal interactions measured do not simply reflect CEOAE I-O function non
      linearity. They may, instead, arise from disturbance of the generator elements
      from their resting state prior to generation of the CEOAE. These results may also
      have general implications relating to cochlear responses to transient stimuli and
      indicate the potential of CEOAEs in probing aspects of cochlear mechanics.

PMID- 10913889
TI  - Simultaneous monitoring of slow cell motility and calcium signals of the guinea
      pig outer hair cells.
AB  - 'Slow' motility (shape changes over seconds to minutes) of the mammalian cochlear
      outer hair cell (OHC) could play a protection role from intense sound pressure
      and is associated with elevation of the cytosolic free Ca(2+) concentration
      ([Ca(2+)](i)). In the present work, a new approach was elaborated using
      fluorescent imaging for continuous monitoring of both [Ca(2+)](i) changes and
      slow motility of OHCs employing the Ca(2+) fluorescent indicator Fura-2. Whole
      OHC fluorescence and that of cell segments were analyzed to discriminate between
      fluorescence changes caused by [Ca(2+)](i) rise and those related to change of
      the cell shape. The reliability of the method was examined by simultaneous
      monitoring of [Ca(2+)](i) and OHC length changes induced by change of buffer
      osmolarity or by increase of KCl concentration. The method revealed that the time
      course of [Ca(2+)](i) increase and rate of cell shortening often do not coincide.
      It was also observed that [Ca(2+)](i) increased in 70 mM KCl more slowly than the
      rate of KCl delivery to OHCs. The comparison of the time courses of [Ca(2+)](i)
      elevation, induced by increase of K(+)/Na(+) ratio and by substitution of Na(+)
      with N-methyl-D-glucamine(+), indicated that the relatively slow kinetics of
      [Ca(2+)](i) increase in the OHC is partially attributed to regulation of Ca(2+)
      homeostasis by the Na(+)/Ca(2+) exchanger.

PMID- 10913890
TI  - Differential protective effects of neurotrophins in the attenuation of noise
      induced hair cell loss.
AB  - The protective efficacy of neurotrophin-3 (NT-3) and brain-derived neurotrophic
      factor (BDNF) at 1 or 10 microg/ml was assessed in guinea pigs exposed to 4 kHz
      octave band noise at 115 dB SPL for 5 h. BDNF, NT-3 or artificial perilymph was
      delivered to the scala tympani via a mini-osmotic pump, beginning 4 days prior to
      noise exposure and continuing for 1 week post-exposure. Protection was assessed
      physiologically by the change in auditory brainstem response (ABR) threshold, and
      histologically by outer hair cell (OHC) survival. There was a statistically
      significant increase in OHC survival and a decrease in ABR threshold shift in
      animals receiving NT-3 at a concentration of 10 microg/ml. In animals receiving 1
      microg/ml NT-3, there was a significant increase in OHC survival in the first row
      of OHC, but no significant change in ABR threshold, relative to control animals.
      In animals treated with BDNF, no significant functional or histological
      protection was observed. The protection afforded by NT-3 (10 microg/ml) treatment
      was similar in magnitude to that reported previously with glial cell line-derived
      neurotrophic factor and suggests that several factors may be involved in the
      protective response.

PMID- 10913891
TI  - Evaluation of a model of the cochlear neural membrane. I. Physiological
      measurement of membrane characteristics in response to intrameatal electrical
      stimulation.
AB  - To understand the auditory neural response to electrical stimuli similar to those
      used in a cochlear implant, it will be necessary to understand the neural
      refraction and summation response kinetics. Evidence exists indicating that the
      cell soma may alter the auditory neural response kinetics and could be the site
      of conduction failure for excitation initiated on the peripheral process. There
      is, however, reason to believe that the excitation site in some healthy, type I
      neurons and in pathological, type III neurons is the central process of the cell.
      To characterize the neural response to activation at a controlled central process
      site, cat auditory neurons were stimulated with an intrameatal electrode, and the
      summation and refraction response kinetics were measured. This approach was used
      to: (1) characterize the behavior of the neural response to central process
      excitation; (2) make comparisons between intrameatal excitation at a known
      central site and scala tympani excitation at an unknown site; and (3) provide
      membrane characterization free from the possible alteration of membrane kinetics
      produced by the cell soma. The membrane kinetics measured using intrameatal
      stimulation differ from those recorded with scala tympani stimulation indicating
      that the mechanisms for scala tympani and intrameatal stimulation differ.

PMID- 10913892
TI  - Evaluation of a model of the cochlear neural membrane. II: comparison of model
      and physiological measures of membrane properties measured in response to
      intrameatal electrical stimulation.
AB  - This study examines existing equation sets describing neural membrane ionic
      currents, such as the Hodgkin-Huxley (1952) equations, used to define the
      membrane currents in a numerical model of the auditory neuron and determines
      their adequacy for modeling the summation and refraction properties of auditory
      neurons in response to electrical stimulation. Specifically, the summation and
      refraction time constants of each equation set are compared to physiological
      measures of these time constants. Since previous studies have shown the cell body
      and peripheral process of the auditory neuron may influence the measurement of
      neural time constants, the physiological time constants used for comparison are
      those which were recorded using intrameatal electrical stimulation. The
      intrameatal electrode should stimulate the neuron in an area where the axon has a
      uniform geometry. Accordingly, the neural model used to duplicate this experiment
      was also of uniform geometry. Of the membrane equation sets evaluated, none was
      clearly superior for modeling both the refraction and summation properties of the
      auditory neuron, though some equation sets were capable of accurately modeling
      either the refraction or the summation properties, provided operating
      temperatures were adjusted to provide appropriate kinetics.

PMID- 10913893
TI  - Representation of vowel stimuli in the ventral cochlear nucleus of the
      chinchilla.
AB  - Responses of neurons in the ventral cochlear nucleus (VCN) of anesthetized
      chinchillas to six synthetic vowel sounds (/a/, /e/, /epsilon/, /i/, /o/ and /u/)
      were recorded at several intensity levels. Stimuli were synthesized with a
      fundamental frequency of 100 Hz or 181.6 Hz and had formant values at integer
      multiples of 100 Hz. Responses came from most neuron types in the VCN (with the
      exception of onset cells with an I-shaped pattern). Population studies, performed
      only on primary-like (PL) and chopper neurons, showed that PL neurons provide a
      better temporal representation than do chopper neurons. At the lowest level of
      stimulation, all neuron types provide an accurate rate-place representation of
      vowel spectra. With an increase in stimulus level, the rate-place representation
      of PL neurons becomes inferior to that of chopper neurons, either sustained
      choppers or transient choppers.

PMID- 10913894
TI  - Early unilateral auditory deprivation increases 2-deoxyglucose uptake in
      contralateral auditory cortex of juvenile Mongolian gerbils.
AB  - The effects of early onset, unilateral conductive hearing loss on tone-induced 2
      deoxyglucose (2-DG) uptake in the auditory cortex of juvenile Mongolian gerbils
      (Meriones unguiculatus) were studied. Atresia of the left ear canal was induced
      at postnatal day 9 (P9) to achieve reversible auditory deprivation prior to onset
      of hearing (around P12). Atresia either persisted (ATR, n=4) or the canal was
      opened 15 min before the 2-DG experiments (RE, n=4) at P27. Control animals were
      either non-deprived (CON, n=4), or their left ears were plugged acutely (PAX,
      n=4). In PAX, 2-DG uptake in primary auditory cortex (AI) and anterior auditory
      field (AAF) was lower in right than in left AI and AAF. In contrast, in ATR and
      RE, uptake was significantly higher on the right side contralateral to the
      atresia. Hence, atresia during early development leads to plastic changes
      resulting in an interhemispheric imbalance of functional metabolism in favor of
      the auditory cortex contralateral to the manipulated ear. Distances between tone
      induced 2-DG labeling in AI and AAF were increased in PAX, but smaller in ATR in
      the right compared to the left hemisphere, suggesting effects of atresia also on
      spatial relations in cortical tonotopic maps.

PMID- 10913895
TI  - Mandated coverage for cancer-screening services: whose guidelines do states
      follow?
AB  - OBJECTIVES: To determine the prevalence and nature of state coverage mandates for
      cancer screening. METHODS: We contacted insurance departments in 50 states,
      Washington, DC, and Puerto Rico for copies of state codes that mandate coverage
      of screening for breast, cervical, prostate, and colorectal cancer by private
      insurers. We further compared mandates, when identified, with American Cancer
      Society (ACS) and U.S. Preventive Services Task Force (USPSTF) guidelines for
      likely sources of screening recommendations. RESULTS: Forty-three states and the
      District of Columbia currently mandate coverage of cancer screening. Breast
      cancer-screening coverage was most frequently mandated (n =44), followed by
      cervical (n =22), prostate (n =18), and colorectal cancer screening (n =1).
      Twenty-three states used ACS guidelines only, 18 states used ACS and non-ACS/non
      USPSTF guidelines, and 3 states used only non-ACS/non-USPSTF guidelines in
      development of coverage mandates. No state screening coverage mandate reflected
      USPSTF-screening guidelines. Of 85 mandates in place, 57 have been passed since
      1990. CONCLUSIONS: Although state mandates for insurer coverage of cancer
      screening are common and increasing, we found noticeable inter- and intra-state
      variation in coverage, selection, and use of screening guidelines.

PMID- 10913896
TI  - A one-year audit of topics and domains in the Journal of the American Medical
      Association and the New England Journal of Medicine.
AB  - BACKGROUND: The relative emphasis that major medical journals give to topic areas
      has a potential effect on priorities in patient care, policy decisions, and
      public awareness. We measured the distribution of topics in two journals, by
      disease categories and domains, over a calendar year. METHODS: All original
      investigations, reviews, editorials, and special articles published in 1998 by
      the Journal of the American Medical Association and the New England Journal of
      Medicine were classified by article type, disease category, and domain. The 12
      domains ranged from basic science to health policy, and included primary and
      secondary prevention. RESULTS: The 1159 articles published in 1998 included 889
      (77%) articles about specific diseases-590 falling within eight specialties-and
      190 (16%) articles on generic topics. Eighty (7%) articles concerned the
      behaviors that cause disease. Primary prevention and screening were the subject
      of 71 (6%) and 29 (3%) articles, respectively. Most of these concerned uncommon
      issues in patient care. Although 27 (2%) articles dealt with essential health
      promotion (e.g., diet, exercise), and none included a study on how to help
      patients to exercise, stop smoking, or eat a healthy diet. In contrast, 451 (39%)
      articles concerned the diagnosis and treatment of patients with disease.
      CONCLUSIONS: The relative emphasis that journals gave to prevention during the
      sample period seems discordant with its importance to patients and public health.
      Potential explanations include poor volume and quality of submitted research and
      editorial concerns about importance and reader appeal.

PMID- 10913897
TI  - Progress toward attainment of the Healthy People 2000 objectives in the U.S.
      Army: measured by health risk appraisal results.
AB  - BACKGROUND: Healthy People 2000 (HP2000) is a national agenda of health promotion
      and disease prevention objectives, with specific health behavior goals in 22
      priority areas. The U.S. Army Health Risk Appraisal (HRA) is a self-administered
      health-habits survey, inquiring about tobacco and alcohol use, physical activity,
      nutrition, and safety-related practices, given to more than 400,000 active-duty
      U.S. Army soldiers in the 1990s. This article compares the health behaviors of
      U.S. Army soldiers, as measured by the HRA, with the HP2000 objectives. METHODS:
      We compared cross-sectional analyses of self-reported health behaviors of active
      duty Army personnel responding to HRA questionnaires in 1991 (n=78,256) and in
      1997-1998 (n=59,771) with corresponding HP2000 objectives. We also calculated
      longitudinal changes for personnel who took more than one HRA (n=86,393).
      RESULTS: By 1997-1998, the Army exceeded HP2000 physical fitness goals by at
      least 50% and also exceeded goals for eating high-fiber foods and using bicycle
      helmets. The Army did not meet goals for nutrition, tobacco use, and seat-belt
      use. CONCLUSIONS: The Army has made good progress toward the HP2000 goals.
      However, improvement is needed to meet the tobacco, nutrition, and safety goals.

PMID- 10913898
TI  - Costs of immunization registries: experiences from the All Kids Count II
      Projects.
AB  - BACKGROUND: Immunization registries are tools to improve and sustain immunization
      coverage rates for our nation's preschool children. Developing a means of
      supporting registries over the long term requires information on costs to operate
      registries. METHODS: To determine the annual cost per child to operate
      immunization registries for the 16 All Kids Count (AKC) II projects, some of the
      most developed registry projects in the United States, we projected a national
      figure for operating registries and compared the figure with a variety of
      potential cost offsets. RESULTS: When the registries are fully operational, the
      average cost per child for the 16 AKC II projects will be $3.91 (range, $1.60 to
      $6.23; interquartile range, $2.91 to $4.81) per year. CONCLUSIONS: Based on the
      AKC study, maintaining a nationwide network of registries for children aged 0 to
      5 will require an estimated $78.2 million. Cost offsets include not having to
      manually retrieve records for school entry, child care, change in provider, and
      Health Plan Employer Data Information Set reports; not having to carry out the
      National Immunization Survey; and prevention of overimmunization. We estimate
      these offsets at $113.8 million annually.

PMID- 10913899
TI  - The cost to providers of participating in an immunization registry.
AB  - INTRODUCTION: The medical and public health communities advocate immunization
      registries as one tool to achieve national immunization goals. Although
      substantial resources have been expended to establish registries across the
      nation, minimal research has been conducted to evaluate provider participation
      costs. METHODS: The objective of this study was to identify the direct costs to
      participate in an immunization registry. To estimate labor and equipment costs,
      we conducted interviews and direct observation at four sites that were
      participating in one of two immunization registries. We calculated mean data
      entry times from direct observation of clinic personnel. RESULTS: The annual cost
      of participating in a registry varied extremely, ranging from $6083 to $24,246,
      with the annual cost per patient ranging from $0.65 to $7. 74. Annual per-patient
      costs were lowest in the site that used an automated data-entry interface. Of the
      sites requiring a separate data-entry step, costs were lowest for the site
      participating in the registry that provided more intensive training and had a
      higher proportion of the target population entered into the registry.
      CONCLUSIONS: Ease of registry interface, data-entry times, and target population
      coverage affect provider participation costs. Designing the registry to accept
      electronic transfers of records and to avoid duplicative data-entry tasks may
      decrease provider costs.

PMID- 10913900
TI  - Does provider prevention orientation influence female patients' preventive
      practices?
AB  - BACKGROUND: Health care provider encouragement for particular preventive
      behaviors is associated with patient adherence, but it is unclear whether a
      provider's overall prevention approach influences whether patients engage in
      recommended preventive measures. We examined whether older women who perceived
      that their health care provider encouraged a particular preventive behavior were
      more likely to follow that recommendation if they also perceived that the
      provider encouraged other preventive behaviors. DATA AND METHODS: The sample
      included 1119 women aged 50 to 79 enrolled in a health maintenance organization.
      We examined associations of reported provider encouragement for post-menopausal
      hormone use, physical activity, fecal occult blood testing (FOBT), and flexible
      sigmoidoscopy with one another and with adherence to these measures according to
      recommended guidelines. RESULTS: Among women reporting provider encouragement for
      physical activity, the likelihood of reporting regular physical activity was
      greater among women who reported encouragement for one other (odds ratio
      [OR]=1.99; confidence interval [CI]=1.35 to 2.95) and at least two other (OR=2.
      38; 95% CI=1.62 to 3.48) preventive measures compared with women who reported no
      other encouragement. The likelihood of reporting adequate counseling for post
      menopausal hormone use was greater among women reporting encouragement for at
      least two other preventive measures compared with those reporting no other
      encouragement. The likelihood of having had an FOBT or sigmoidoscopic examination
      was related to encouragement for those procedures, but not with greater
      encouragement for other preventive measures. CONCLUSIONS: Patient perceptions of
      a provider's overall preventive practice approach may influence whether patients
      engage in recommended preventive practices, particularly for lifestyle factors.

PMID- 10913901
TI  - Introduction. Interactive health communication in preventive medicine.

PMID- 10913902
TI  - Interactive health communication in preventive medicine: internet-based
      strategies in teaching and research.
AB  - Interactive health communication using Internet technologies is expanding the
      range and flexibility of intervention and teaching options available in
      preventive medicine and the health sciences. Advantages of interactive health
      communication include the enhanced convenience, novelty, and appeal of computer
      mediated communication; its flexibility and interactivity; and automated
      processing. We outline some of these fundamental aspects of computer-mediated
      communication as it applies to preventive medicine. Further, a number of key
      pathways of information technology evolution are creating new opportunities for
      the delivery of professional education in preventive medicine and other health
      domains, as well as for delivering automated, self-instructional health behavior
      change programs through the Internet. We briefly describe several of these key
      evolutionary pathways. We describe some examples from work we have done in
      Australia. These demonstrate how we have creatively responded to the challenges
      of these new "information environments," and how they may be pursued in the
      education of preventive medicine and other health care practitioners and in the
      development and delivery of health behavior-change programs through the Internet.
      Innovative and thoughtful applications of this new technology can increase the
      consistency, reliability, and quality of information delivered.

PMID- 10913903
TI  - Interactive communication strategies: implications for population-based physical
      activity promotion.
AB  - Physical inactivity is a recognized independent risk factor for the development
      of cardiovascular disease. However, a large proportion of the U.S. population
      does not participate in regular physical activity, and research has shown that
      without intervention, most people remain sedentary. Thus, an urgent need exists
      for developing effective interventions to promote physical-activity adoption and
      maintenance. Additionally, it is important that these interventions can be
      disseminated to the large population of sedentary individuals. To be
      disseminable, physical-activity interventions must move beyond reliance on
      strictly face-to-face modes and begin to more fully use newer technologies, such
      as the Internet. This article summarizes the progress made in promoting physical
      activity with interactive communications. We also delineate areas for future
      research.

PMID- 10913904
TI  - PACE+: interactive communication technology for behavior change in clinical
      settings.
AB  - BACKGROUND: Interactive health communication technologies have the potential to
      eliminate or greatly reduce many of the barriers to delivery of preventive
      services. This paper describes the process of developing and evaluating
      interactive health communication programs for primary care settings. We present
      as examples the Patient-centered Assessment and Counseling for Exercise plus
      Nutrition (PACE+) programs, designed to promote physical activity and healthy
      nutrition with adolescents and adults. METHODS: The PACE+ programs use
      interactive communication technology to screen multiple behaviors, prioritize
      areas for intervention, and initiate intervention. Patient information is
      synthesized for ease of use by clinicians. The patient completes the program on a
      computer in the clinic waiting room before the provider encounter. Acceptability
      of the program was evaluated with adolescents (n=252), adults (n=285), and their
      health care providers. RESULTS: The PACE+ programs were developed, evaluated,
      modified, and re-evaluated. Feasibility testing indicated that a diverse group of
      adolescents and adults found the PACE+ computer programs acceptable.
      Modifications to shorten and refine the programs were identified. CONCLUSIONS:
      Development of interactive health technologies is an iterative process dependent
      on feedback from intended users and systems of care. Interactive health
      communication technologies can be incorporated into clinical settings.

PMID- 10913905
TI  - Information technology and the future of preventive medicine: potential,
      pitfalls, and policy.

PMID- 10913907
TI  - Is an ounce of prevention enough? Prescribing for the health of the public.

PMID- 10913906
TI  - Politics trumps science: rethinking state-mandated benefits.

PMID- 10913908
TI  - IPCS guidelines for the monitoring of genotoxic effects of carcinogens in humans.
      International Programme on Chemical Safety.
AB  - The purpose of these guidelines is to provide concise guidance on the planning,
      performing and interpretation of studies to monitor groups or individuals exposed
      to genotoxic agents. Most human carcinogens are genotoxic but not all genotoxic
      agents have been shown to be carcinogenic in humans. Although the main interest
      in these studies is due to the association of genotoxicity with carcinogenicity,
      there is also an inherent interest in monitoring human genotoxicity independently
      of cancer as an endpoint. The most often studied genotoxicity endpoints have been
      selected for inclusion in this document and they are structural and numerical
      chromosomal aberrations assessed using cytogenetic methods (classical chromosomal
      aberration analysis (CA), fluorescence in situ hybridisation (FISH), micronuclei
      (MN)); DNA damage (adducts, strand breaks, crosslinking, alkali-labile sites)
      assessed using bio-chemical/electrophoretic assays or sister chromatid exchanges
      (SCE); protein adducts; and hypoxanthine-guanine phosphoribosyltransferase (HPRT)
      mutations. The document does not consider germ cells or gene mutation assays
      other than HPRT or markers of oxidative stress, which have been applied on a more
      limited scale.

PMID- 10913909
TI  - Is there a therapeutic opportunity to either prevent or treat osteopenic
      disorders by inhibiting marrow adipogenesis?
AB  - Bone marrow stromal cells can undergo adipogenesis or osteoblastogenesis in vitro
      and in vivo. This review explores the stromal cell's differentiation plasticity
      in the context of osteoporosis and other metabolic bone disorders. Attention is
      focused on the apparent reciprocal relationship that is postulated to exist
      between the adipocyte and osteoblast phenotypes. The signal transduction pathways
      implicated in this process are evaluated as potential targets for therapeutic
      intervention and drug design.

PMID- 10913911
TI  - Anabolic effects of basic fibroblast growth factor in the tibial diaphysis of
      ovariectomized rats.
AB  - The purpose of this study was to determine the effects of basic fibroblast growth
      factor (bFGF) on cortical bone in ovariectomized (ovx) rats. Female Sprague
      Dawley rats were subjected to sham surgery or ovariectomy at 3 months of age and
      maintained untreated for 2 months after surgery. Polyurethane catheters were then
      inserted in the jugular veins of all rats for daily intravenous treatments with
      vehicle or bFGF at doses of 100 or 200 microg/kg for 7 or 14 days. Other groups
      of ovx rats were killed at 7 or 14 days after withdrawal of treatment with the
      higher dose of bFGF. Quantitative bone histomorphometry was performed in
      undecalcified cross sections of the tibial diaphysis. Cortical bone area was
      nearly the same in vehicle-treated control and ovx rats, but a small,
      statistically significant increase in this structural variable was observed in
      ovx rats treated with both doses of bFGF. This small increase in cortical bone
      area was maintained at 7 days after withdrawal of bFGF treatment. Fluorochrome
      based analyses of periosteal and endocortical bone formation were inconclusive
      due to an inhibitory effect of bFGF on bone mineralization. However, a marked
      increase in fluorescent bone area was observed within the marrow cavity of bFGF
      treated OVX rats during the withdrawal period. The results indicate that
      treatment of OVX rats with bFGF for only 7 to 14 days augments cortical bone mass
      and induces formation of bone spicules within the marrow cavity of the tibial
      diaphysis. These bone anabolic effects of the growth factor support its
      consideration as a potential osteoporosis therapy.

PMID- 10913910
TI  - Expression of the developmental markers STRO-1 and alkaline phosphatase in
      cultures of human marrow stromal cells: regulation by fibroblast growth factor
      (FGF)-2 and relationship to the expression of FGF receptors 1-4.
AB  - Autologous marrow stromal cells have been proposed as an adjuvant in the
      treatment of bone defects and diseases. This will require the development of
      culture conditions that permit their rapid expansion ex vivo while retaining
      their potential for further differentiation. Fibroblast growth factor (FGF)-2 has
      been proposed as a candidate for the ex vivo expansion of cells with enhanced
      osteogenic potential, and we have explored this possibility further using cells
      obtained from a large cohort of adult human donors. Treatment with FGF-2 (0.001
      2.5 ng/mL) had no detectable effect on colony formation, but markedly increased
      their proliferative potential and that of their immediate progeny, as shown by
      the increases in colony size and cell number. Based on the observed increase in
      the expression of the developmental markers STRO-1 and alkaline phosphatase (AP),
      a major target for the actions of FGF-2 appears to be the more primitive cells of
      the osteoblast lineage, and that, when added in combination with the synthetic
      glucocorticoid dexamethasone (Dx), it interacts positively to promote further
      cell maturation. The maintenance of adequate levels of ascorbate was shown to be
      a critical component in determining the nature of the effect of FGF-2 on AP
      expression. Variation in the response (predominantly in the magnitude and/or
      sensitivity) of the cultured cell populations to treatment with FGF-2 was
      apparent, but a preliminary analysis indicated that this was not due to
      differences in the age or gender of the donors used. The cultured cell
      populations were found to express multiple FGF receptors (FGFRs; 1-4) and the
      observed changes in the spectrum and abundance of FGFRs expressed in relation to
      that of STRO-1 and AP are consistent with their expression being developmentally
      regulated during the process of osteogenic differentiation. These results provide
      novel insights into the mechanism of action of FGF-2 on human cells of the
      osteoblast lineage and support the use of this factor, alone or in combination
      with Dx, for the rapid, ex vivo expansion of cell populations with enhanced
      osteogenic potential.

PMID- 10913912
TI  - Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age.
AB  - The primary aim of the investigation was to assess the relationship between whole
      body fat expressed as a percentage of body weight with whole-body bone mineral
      content relative to age and anthropometry. Sixty females between 10 and 19 years
      of age were recruited to this cross-sectional study, which included measurements
      of weight and height and whole-body fat and bone mineral content using dual
      energy X-ray absorptiometry. To assess bone mineral content, data were expressed
      as a weight or standard deviation scores using age and bone area. Relationships
      between outcome variables were determined using multiple correlation analysis
      followed by multiple linear regression with age, weight, height, and fat as
      predictor variables for outcomes of bone mineral content and density. Correlation
      analysis indicated that whole-body fat expressed as a percent was significantly
      related to weight (p < 0.01), but was not related to age or bone mineral content
      or density unless bone mineral content was corrected to age or bone area using
      standard deviation scores. In addition, body fat was associated with bone area
      for age and height (p < 0.01). However, multiple linear regression yielded
      opposite results. When included in regression, body fat had a negative impact on
      bone mineral content (p = 0.003), mineral content corrected to bone area (p =
      0.02), and bone density (p = 0.003), while age, weight, and height had positive
      impacts on these outcome measurements. The data suggest that for younger
      children, the relative influence of percent body fat will be greater and could be
      linked with suboptimal attainment of peak bone mass. The females in this study
      appeared to be within reference limits for percent body fat. However, greater
      amounts of body fat relative to weight could be a marker for lifestyles that do
      not support attainment of optimal peak bone mass.

PMID- 10913914
TI  - Oim mice exhibit altered femur and incisor mineral composition and decreased bone
      mineral density.
AB  - To investigate the role of the pro alpha 2(I) collagen chains of type I collagen
      in mineralization we used the oim (osteogenesis imperfecta model) mouse as our
      model system. The oim/oim mouse (homozygous for a null mutation in its COL1A2
      gene of type I collagen) fails to synthesize functional pro alpha 2(I) collagen
      chains, synthesizing only homotrimers of pro alpha 1(I) collagen chains. To
      evaluate the role of pro alpha 2(I) collagen in type I collagen
      structure/function in mineralized tissues, we examined age-matched oim/oim,
      heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisors for mineral
      composition (calcium, phosphorus, magnesium, fluoride, sodium, potassium, and
      chloride) by neutron activation analyses (NAA), and bone mineral content (BMC)
      and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DEXA) in a
      longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim
      femurs had significant differences in magnesium, fluoride, and sodium content as
      compared with +/+ mouse femurs, and oim/oim teeth had significant differences in
      magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was
      also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared
      with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had
      significantly reduced BMC and BMD as compared to oim/+ and +/+ mice. Serum and
      urine calcium, magnesium, and phosphorus levels, and Ca(47) absorption across the
      gut were equivalent in oim/oim and +/+ mice, with no evidence of hypercalciuria.
      These studies suggest that the known decreased biomechanical properties of
      oim/oim bone reflect both altered mineral composition as well as the decreased
      BMD, which further suggests that the presence of alpha2(I) chains plays an
      important role in mineralization.

PMID- 10913915
TI  - Osteoblastic networks with deficient coupling: differential effects of magnetic
      and electric field exposure.
AB  - A gap junction-deficient cell line was utilized to test whether intercellular
      coupling plays a significant role in modulating the influence of biophysical
      stimuli such as extracellular electrical currents. ROS 17/2.8 cells, an
      osteosarcoma cell line, along with a control transfected cell line and a connexin
      43-gap junction-deficient cell line, were exposed to a time-changing magnetic
      flux (30 Hz, 1.8 milliTesla) sufficient to induce an electric field in the
      cultures on the order of 2 mV/m. Field exposure inhibited cell growth independent
      of gap junctional coupling, while alkaline phosphatase activity was found to be
      dependent on gap junctional coupling. These findings can be interpreted to
      suggest that magnetic and electric field exposures have differential effects on
      cell cultures, with magnetic field exposure inhibiting cell growth through a
      mechanism independent of gap junctional coupling, while the alteration in enzyme
      activity appears to be stimulated by the induced electric field in a gap junction
      dependent manner.

PMID- 10913913
TI  - In vivo regulation of apoptosis in metaphyseal trabecular bone of young rats by
      synthetic human parathyroid hormone (1-34) fragment.
AB  - Osteoblast differentiation and function can be studied in situ in the metaphysis
      of growing long bones. Proliferation and apoptosis dominate in the primary
      spongiosa subjacent to the growth plate, and differentiation and function
      dominate in the proximal metaphysis. Apoptosis of osteocytes dominates at the
      termination of the trabeculae in diaphyseal marrow. As parathyroid hormone
      regulates all phases of osteoblast development, we studied the in vivo regulation
      by human parathyroid hormone (1-34) (PTH) of apoptosis in bone cells of the
      distal metaphysis of young male rats. Rats were given PTH at 80 microg/kg per
      day, once daily, for 1-28 days. Bone cells were defined for flow cytometry as
      PTH1-receptor-positive (PTH1R(+)) and growth factor-receptor-positive (GFR(+))
      cells. Apoptotic cells stained positive for either TdT-mediated dUTP-X nick end
      labeling (TUNEL) or annexin V (annV(+)) were detected by either flow cytometry or
      immunohistochemistry. Apoptosis was also assessed at the tissue level by RNAse
      protection and caspase enzyme activity assays. PTH increased apoptotic
      osteoblasts in the proliferating zone and apoptotic osteocytes in the terminal
      trabecular zone, by 40%-60% within 2-6 days of PTH treatment, but values became
      equivalent to controls after 21-28 days of treatment. This transient increase was
      confirmed in PTH1R(+), GFR(+) bone cells isolated by flow cytometry. There was no
      detectable change in the steady-state mRNA levels of selected apoptotic genes.
      Starting at 3 days, at the tissue level, PTH inhibited activity of caspases,
      which recognize the DEVD peptide substrate (caspases 2, 3, and/or 7), but not
      those caspases recognizing LEHD or YVAD peptide sequences. We speculate that the
      localized and tissue level effects of PTH on apoptosis can be explained on the
      basis of its anabolic effect on bone. The transient increase in apoptosis in the
      proliferating zone and terminal trabecular zone may be the result of the
      increased activation frequency and bone turnover seen with daily PTH treatment.
      As once-daily PTH increases the number of differentiated osteoblasts, and as
      these and hematopoietic marrow cells dominate metaphyseal tissue, inhibition of
      caspase activity may contribute to their prolonged survival, enabling extension
      of trabecular bone into the diaphyseal marrow to increase bone mass.

PMID- 10913916
TI  - Mechanical strain activates estrogen response elements in bone cells.
AB  - The involvement of the estrogen receptor in the early responses of bone cells to
      mechanical strain was investigated by subjecting subconfluent monolayer cultures
      of ROS.SMER #14 cells (ROS 17/2.8 cells stably transfected with additional ER
      alpha) to 17 beta-estradiol or a single short period of dynamic mechanical strain
      (600 cycles, 1 Hz). The basal proliferation rate of ROS.SMER #14 cells was
      similar to ROS 17/2.8 cells, whose proliferative responsiveness to strain and
      estrogen is similar to that of primary cultures of rat long bone-derived
      osteoblasts. At peak strains of 3400 mu epsilon, strain-related proliferation in
      ROS.SMER #14 cells was 1.4 times that of ROS 17/2.8 cells. At 10(-8) mol/L, 17
      beta-estradiol-related proliferation was nearly twice greater. The ROS.SMER #14
      cells were transiently transfected with an estrogen-responsive reporter, 2ERE-pS2
      CAT, containing two consensus estrogen response elements (ERE) linked to a
      chloroamphenicol acetyl transferase gene. Strain increased normalized ERE-CAT
      activity threefold and estradiol (10(-8) mol/L) sixfold. Both strain-related and
      estradiol-related increases in proliferation and ERE-CAT activity were blocked by
      the estrogen antagonist ICI 182,780 (10(-6) mol/L). These data show that strain
      as well as estrogen stimulates increased proliferation in ROS 17/2.8 cells and
      increased ER alpha-related ERE activity in ROS cells transfected with ER alpha.
      Proliferation is greater in the cells with more estrogen receptors. Both strain-
      and estrogen-related proliferation and ERE activity are blocked by the estrogen
      antagonist ICI 182,780. This indicates that ROS cells' early responses to
      mechanical strain involve ER alpha and estrogen-responsive genes.

PMID- 10913917
TI  - Arachidonic acid for loading induced prostacyclin and prostaglandin E(2) release
      from osteoblasts and osteocytes is derived from the activities of different forms
      of phospholipase A(2).
AB  - Mechanical loading of bone stimulates resident bone cells to produce prostacyclin
      (PGI(2)) and prostaglandin (PG)E(2) by a mechanism that can be differentially
      regulated by ion channel blockers. We have investigated differences in the
      loading-related PG production mechanisms in rat ulnae explants loaded ex vivo.
      Loading and aluminium fluoride (AlF(3), a nonselective activator of G-proteins)
      both increased PGI(2) and PGE(2) release into culture medium. Pertussis toxin
      (PTX) blocked loading-related release of PGE(2), but not PGI(2), while
      isotetrandrine, an inhibitor of G-protein-mediated activation of phospholipase
      (PL)A(2), abolished the loading-related release of both PGs. This suggests both
      PTX-sensitive and -insensitive G-protein-dependent, PLA(2)-mediated mechanisms
      for loading-related PG production. Blockade of secretory (s)PLA(2) activity
      prevented loading-related release of PGE(2) and PGI(2), whereas inhibition of
      cytosolic (c)PLA(2) activity blocked loading-related release of PGE(2) alone.
      cPLA(2) was localized immuno-cytochemically to osteoblasts, but not to
      osteocytes. sPLA(2) was localized to osteocytes and osteoblasts. Exogenous type
      IA sPLA(2) and type-IB sPLA(2) stimulated significant increases in PGE(2) and
      PGI(2) release. PTX reduced the release of both PGs stimulated by type IA PLA(2),
      but not type IB. Furthermore, inhibition of protein kinase C (PKC) activity
      blocked loading-related release of PGE(2), but not that of PGI(2). These data
      suggest that loading-related release of PGI(2) and PGE(2) utilizes arachidonic
      acid derived from the activity of different PLA(2)s. In osteocytes and
      osteoblasts, arachidonic acid for PGI(2) synthesis is liberated by PTX
      insensitive G-protein-dependent sPLA(2) alone. In osteoblasts, arachidonic acid
      for PGE(2) synthesis is released by PTX-sensitive, G-protein-dependent, cPLA(2)
      mediated activity, which also requires upstream sPLA(2) and PKC activities.

PMID- 10913918
TI  - Effects of exercise and disuse on bone remodeling, bone mass, and biomechanical
      competence in spontaneously diabetic female rats.
AB  - Diabetes is associated with low bone formation. In this study we investigate the
      effect of additional or reduced mechanical loading on indices of bone formation
      and resorption, bone mass, and biomechanical properties in spontaneously diabetic
      BB rats. Female diabetic (mean age 13 weeks) and age-matched control rats were
      each allocated to three experimental groups: no-intervention; supervised running
      exercise program (Ex); and unloading induced by unilateral sciatic neurectomy
      (USN). The study period was 8 weeks. We measured biochemical parameters of bone
      formation (plasma osteocalcin) and resorption (urinary deoxypyridinoline [Dpd]);
      bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) at
      middiaphyseal and metaphyseal regions of the femur; histomorphometry of the
      proximal tibial metaphysis (PTM); and biomechanical properties of the femur
      (neck, diaphysis, and metaphysis) and lumbar vertebra (L-5). In nondiabetic rats,
      Ex did not affect parameters of bone formation/resorption and BMD, and had little
      effect on biomechanical properties. USN increased Dpd excretion, whereas there
      was a decreased trabecular bone formation rate (BFR) on morphometry of PTM in
      both paralyzed and intact limbs. Compared with intact limbs, paralyzed limbs of
      USN rats showed decreased trabecular bone volume at the PTM, and decreased BMD
      and biomechanical properties at the distal femoral metaphysis (DFM) and, to a
      lesser extent, femoral neck. Diabetic rats of the three experimental groups had
      low plasma osteocalcin levels and Dpd excretion, as well as low BFR on
      morphometry. The BMD and biomechanical properties of both femur and L-5 were
      unchanged in diabetic rats. Diabetic Ex rats, however, showed a lower maximum
      load and stress at DFM than control Ex rats. Diabetic USN rats showed no increase
      in Dpd excretion; their paralyzed limbs showed decreased maximum load at DFM, but
      there was no significant decrease in trabecular bone volume at PTM or BMD at DFM.
      Thus, the running exercise does not affect low bone formation in diabetic rats;
      however, trabecular bone loss caused by disuse is less pronounced in diabetic
      rats, probably as a result of low bone resorption.

PMID- 10913919
TI  - Asymmetric adaptive modeling of central tarsal bones in racing greyhounds.
AB  - Fatigue fracture of the cuboidal bones of the foot, especially the navicular
      tarsal bone, is common in athletes and dancers. The racing greyhound is a
      naturally occurring animal model of this injury because both microcracking and
      complete fracture occur in the right central (navicular) tarsal bone (CTB). The
      right limb is on the outside when racing in a counter-clockwise direction on
      circular tracks, and is subjected to asymmetric cyclic compressive loading. We
      wished to study in more detail adaptive modeling in the right CTB in racing
      greyhounds. We hypothesized that cyclic asymmetric loading of a cuboidal bone
      induced by racing on a circular track would induce site-specific bone adaptation.
      We also hypothesized that such an adaptive response would be attenuated in
      greyhounds that were retired from racing and no longer subjected to cyclic
      asymmetric loading. Central tarsal bones from racing greyhounds (racing group, n
      = 6) and retired greyhounds being used for breeding (nonracing group, n = 4) were
      examined using quantitative computed tomography (CT). Bone mineral density (BMD)
      was determined in a 3-mm diameter region-of-interest (ROI) in six contiguous 1-mm
      thick sagittal CT slices of each CTB. Bones were subsequently examined
      histomorphometrically and percentage bone area (B.Ar./T.Ar., %) was determined in
      10 ROI from dorsal to plantar in a transverse plane, mid-way between the proximal
      and distal articular surfaces. The BMD of the right CTB was greater than the left
      in all greyhounds (p < 0. 001). In comparing ipsilateral limbs between groups,
      BMD of the racing group was greater than the nonracing group for each side (p <
      0.005). In sagittal plane histologic sections, bone in the dorsal region of the
      right CTB had undergone adaptive modeling, through thickening and compaction of
      trabeculae. B.Ar./T.Ar., % in the right CTB of the racing group was greater than
      in the contralateral CTB (p < 0.001), and the ipsilateral CTB of the nonracing
      group (p < 0.001). In the nonracing group, B.Ar./T.Ar., % in the right CTB was
      not significantly different from left CTB (p > 0.8; power = 80% at Delta = 48%).
      It was concluded that greyhounds racing on circular tracks develop site-specific
      bone adaptation with compaction of trabecular bone and increase in BMD in the
      right CTB in particular, the most common site for fatigue fracture. Our data also
      suggested that partial reversal of this adaptive process occurred in retired,
      nonracing greyhounds, after cessation of asymmetric cyclic loading at racing
      speed. Racing greyhounds provide a model in which to study fatigue fracture and
      adaptation of cuboidal foot bones subjected to cyclic loading.

PMID- 10913920
TI  - Expression of the small leucine-rich proteoglycan osteoadherin/osteomodulin in
      human dental pulp and developing rat teeth.
AB  - Because the extracellular matrices of dentin and bone are composed mainly of type
      I collagen, their characteristics are determined by the nature of noncollagenous
      proteins (NCPs). Among these NCPs, some proteoglycans (PGs) belong to the small
      leucine-rich proteoglycans (SLRPs). Recently, osteoadherin (OSAD) has been
      described as a new member of this family, that is expressed by mature bovine
      osteoblasts. Here, we report the expression of OSAD messenger RNA (mRNA) in human
      dental tissues and during the development of rat molars, using in situ
      hybridization. For this purpose, we constructed a probe for OSAD mRNA transcripts
      from human odontoblast cells cultured in vitro. Our results indicate that the
      mature human odontoblasts overexpress the OSAD gene as compared with cells
      present in the pulp core. In rat developing molars, mRNA transcripts were first
      detected in alveolar bone in 19-day-old embryos. At the same age, no signal was
      detected in any cell of the first molar. In more mature teeth (newborn and 2-day
      old rats), OSAD expression starts in the polarized odontoblasts and increases in
      the secretory and mature odontoblasts, respectively. Interestingly, a similar
      pattern of expression was observed in the ameloblast layer responsible for the
      deposition of enamel mineralized matrix. Together, these results lead us to
      speculate that OSAD may be implicated in biomineralization processes.

PMID- 10913921
TI  - Trabecular architecture in women and men of similar bone mass with and without
      vertebral fracture: I. Two-dimensional histology.
AB  - While osteoporosis is characterized by a low bone mass there is a well-recognized
      overlap in bone mineral density (BMD) measurements between groups of subjects
      with and without vertebral fracture. To investigate whether differences in
      trabecular architecture may contribute to the presence or absence of fractures
      independent of the bone mass, fracture and nonfracture groups matched for age,
      gender, and BMD were assembled. Transiliac biopsies and corresponding lumbar
      spine BMD measurements from 31 women and 16 men with vertebral fracture were
      compared with those from 22 women and 11 men without fracture. Lumbar BMD (L1-4)
      was measured using a Hologic 2000 densitometer. The lumbar BMD was similar in
      women with and without fracture (0.63 g/cm(3) +/- 0.10 SD and 0.71 g/cm(3) +/-
      0.17 SD, n.s.) and in men with and without fracture (0.72 g/cm(3) +/- 0.12 SD and
      0.76 g/cm(3) +/- 0.17 SD, n.s.). Undecalcified iliac crest biopsy sections, 8
      microm thick, were analyzed for remodeling variables and trabecular architecture
      using OsteoMeasure and TAS image analysis systems. No significant difference was
      found in either gender between fracture and nonfracture groups in percent bone
      volume (mean 10% in all groups), or in the wide range of remodeling and
      architectural variables measured, including the trabecular width, number, and
      separation, mean trabecular plate density and fractal dimension, as well as
      several indirect indices of connectivity including the node:terminus ratio,
      marrow star volume, and trabecular pattern factor. On the basis of this evidence
      it was concluded that there is no difference in the trabecular architecture
      between patients with crush fracture and controls when account is taken of bone
      mass. This suggests that microanatomical disruption is a predictable intrinsic
      feature of bone loss. However, there remains the possibility that the two
      dimensional character of the structural deterioration measured indirectly is not
      sufficiently sensitive for the complex cancellous system. This is considered
      further in part II.

PMID- 10913923
TI  - Serum type I collagen breakdown product (serum CTX) predicts hip fracture risk in
      elderly women: the EPIDOS study.
AB  - We report the predictive value for hip fracture of a new marker of bone
      resorption, serum C-telopeptide of type I collagen (CTX), measured on a new
      automated analyzer, Elecsys. Baseline urinary and serum samples from 212 patients
      who subsequently had a hip fracture and from 642 controls were analyzed in a
      nested case control study within the EPIDOS prospective cohort. Each fracture
      patient was matched with three control patients of the same age who did not
      fracture. Mean follow-up was 3.3 years (maximum 4.9 years). We measured urinary
      CTX, urinary free deoxypyridinoline, and serum CTX. Urinary markers were assessed
      to know whether the magnitude of prediction of hip fracture by this serum marker
      was similar compared with that given by urinary markers. In the whole group,
      serum CTX was not predictive of hip fracture risk. When the analysis was
      restricted to samples taken in the early afternoon (between 1 and 2 P.M.),
      representing 115 fracture cases and 293 controls, serum CTX was significantly
      predictive with a relative hazard of 1.86 (95% confidence interval 1.01-3.76) for
      values above the premenopausal range (mean + 2 SD). For comparison, in the whole
      group, the relative hazard for fracture of women having a T-score >/= 2 for
      urinary CTX and free deoxypyridinoline was 1.67 (1.19-2.32), and 2. 07 (1.49
      2.9), respectively. Serum CTX from morning samples did not predict hip fractures
      probably because it was not controlled for time and fasting/nonfasting state. We
      conclude that serum CTX sampled under controlled conditions significantly
      predicts the subsequent risk of hip fracture in ambulatory elderly women, with
      the same magnitude as urinary markers of resorption.

PMID- 10913922
TI  - Trabecular architecture in women and men of similar bone mass with and without
      vertebral fracture: II. Three-dimensional histology.
AB  - We recently developed a simple and inexpensive method that complements
      established bone histomorphometry procedures by enabling the two-dimensional
      imaging of cancellous bone to be viewed within its three-dimensional context with
      the marrow tissue in place and without detriment to the material for other
      histological purposes. The method, based on the preparation and superficial
      staining of slices 300 microm thick, enables "real" (i.e., unstained) trabecular
      termini to be separated from "artifactual" (i.e., stained) termini, providing a
      direct measure of cancellous connectivity in osteopenic bone. The technique was
      applied to osteopenic age-matched, white, postmenopausal women (31 with and 22
      without vertebral compression fractures) with a similar bone status, as measured
      at the spine by absorptiometry and at the iliac crest by histology (see part I of
      this study). Despite the similarity in the mass of trabecular bone at either
      site, the results showed a significant difference (p < 0. 05) in the number of
      "real" trabecular termini between the groups, such that the fracture group had
      almost four times as many termini (mean +/- SE: 1.98 +/- 0.51/30 mm(2)) at the
      iliac crest as the nonfracture group (mean +/- SE: 0.53 +/- 0.31/30 mm(2)).
      Previous histomorphometry of the same material failed to detect a structural
      distinction between the two groups using established variables. It was concluded
      that a mass-independent trabecular discontinuity contributes to skeletal failure
      and that determination of the number of "real" disconnections (i.e., unstained
      termini) by the direct method proposed may provide a more sensitive discriminant
      of fracture than the present indirect procedures. A group of fracture and
      nonfracture men (see part I) suggested a similar distinction (fracture: 0.69 +/-
      0.30/30 mm(2); nonfracture: 0.18 +/- 0.18/30 mm(2)), although the difference was
      not significant.

PMID- 10913924
TI  - Quantitative ultrasound and dual X-ray absorptiometry measurements of the
      calcaneus in patients on maintenance hemodialysis.
AB  - It has been suggested that quantitative ultrasound measurements (QUS), which
      reflect mainly bone density, could be influenced by bone micro-architecture. The
      aim of the study was to assess whether the relationship of QUS to dual X-ray
      absorptiometry (DXA) would reflect abnormalities of bone structure observed in
      renal osteodystrophy. QUS and bone mineral density of the calcaneus (BMDc) were
      measured by DXA in 30 patients on maintenance hemodialysis and 34 age- and gender
      matched controls. QUS parameters and BMDc were significantly lower in
      hemodialysis patients than in controls (speed of sound [SOS] and broadband
      ultrasound attenuation [BUA], p = 0. 030; stiffness, p = 0.003; BMDc, p = 0.006).
      Bone measurements were not correlated with serum parathyroid hormone (PTH). The
      regression lines of SOS, BUA, and stiffness to BMDc were not significantly
      different from that of the controls. When dividing the patients into two
      subgroups according to their median PTH (203 pg/mL), the slopes of the regression
      lines of BUA to BMDc were significantly different between these two subgroups (p
      = 0.052). The slope of the subgroup with PTH </= 203 pg/mL was significantly
      different from that of the controls (p = 0.030). In conclusion, QUS of the
      calcaneus can be used for bone assessment in patients on maintenance
      hemodialysis. The differences in the slopes of patients with a less pronounced
      degree of hyperparathyroidism compared with patients with a higher degree of
      hyperparathyroidism and to controls suggest that BUA of the calcaneus contains
      information on bone complementary to DXA measured at the same site. The clinical
      relevance of this finding is presently unclear.

PMID- 10913925
TI  - Timing of food intake has a marked effect on the bioavailability of clodronate.
AB  - Because of the low and variable bioavailability of bisphosphonates and the huge
      effect of food on their gastrointestinal absorption, it is of utmost importance
      to know the optimal timing of drug intake in relation to food intake. We
      investigated the effect of time on the bioavailability of clodronate when the
      drug was administered 2, 1, or 0.5 h before breakfast, with breakfast, or 2 h
      after breakfast (in the middle of a 4-h fast). The study was conducted as a
      single-center, open, balanced, randomized, crossover pharmacokinetic study in 31
      healthy subjects aged 21 to 34 years. The volunteers participated in five
      different sessions with 800 mg of oral clodronate, and these sessions were
      separated by washout phases, each for at least 1 week. The primary
      pharmacokinetic variables were the area under the serum concentration time curve
      in 24 h (AUC(0-24)) for clodronate and the maximal concentration of clodronate in
      serum (C(max)). Clodronate was absorbed rather similarly when taken in the
      morning on an empty stomach 2, 1, or 0.5 h before breakfast, but because the best
      absorption occurred (as expected) when the drug was taken 2 h before breakfast,
      this scheme served as the reference treatment. As evaluated by area under the
      serum concentration time curves, the dose-breakfast interval of 1 h scarcely
      reduced absorption from the reference treatment level (relative absorption 91%, p
      = 1.0). Compared with the reference treatment, clodronate was absorbed with 69%
      efficacy (p = 0.65) when breakfast followed only 0.5 h later. The dose-breakfast
      intervals of 0.5 and 1 h did not differ significantly from each other (p = 0.85).
      Absorption was, however, only 34% (p < 0.0001) of the optimum when the drug was
      taken 2 h after breakfast, and only 10% of optimal when clodronate was taken with
      breakfast (p < 0.0001). In conclusion, it can be recommended to take Bonefos
      capsules in the morning on an empty stomach at least 0.5 h before breakfast.

PMID- 10913926
TI  - A novel mechanism for induction of increased cortical porosity in cases of
      intracapsular hip fracture.
AB  - It has been suggested that, in hip fracture, the cortex on the inferoanterior
      (IA) to superoposterior (SP) axis is thinned and shows increased porosity. This
      is dependent on the presence of giant canals (i.e., diameter >385 microm), which
      are related to clusters of remodeling osteons. To investigate further the
      relationship between remodeling and bone loss, osteonal diameter (On.Dm), wall
      thickness (W.Th), osteoid width (O.Wi), and extent (OS) were measured in femoral
      neck biopsies from 12 female intracapsular hip fracture cases and 11 age- and
      gender-matched controls. Over 83% of giant canals were "composite" osteonal
      systems in which a single canal was surrounded by multiple packets of osteonal
      bone. Among smaller canals, over 80% of systems had a canal encircled by a single
      cement line containing one packet of bone ("simple"). Composites were nearly
      twice as prevalent in fractures (fracture cases 9.8 +/- 0.7/25 mm(2), controls
      5.3 +/- 0.4/25 mm(2), p < 0. 0001), and were dependent (R(2) = 0.52) on femoral
      neck region (p = 0.0008) and the regional distribution of clusters of remodeling
      osteons (p = 0.0045). Both the inferior (I) and anterior (A) regions had an
      elevated number of composites (I: 263% of control values, p = 0.0054; A: 202% of
      control values, p = 0.0092). On.Dm was similar in fracture cases and controls
      (simple: fracture cases 183 +/- 3 microm, controls 191 +/- 4 microm; composites:
      fracture cases 446 +/- 13 microm, controls 460 +/- 13 microm). W.Th in simples
      was similar in fracture cases and controls (fracture cases 51 +/- 0.8 microm,
      controls 49 +/- 0.7 microm), but composites had significantly (p < 0. 0001)
      thinner walls, with the reduction in fracture cases (31%) being twice that of
      controls (12%, p < 0.0001). There were no differences in O.Wi. It was unusual for
      osteoid to fully surround the composite canal surface; OS was 38% lower in
      composite than simple canals (p < 0.0001). This study indicates that, in the
      femoral neck cortex, the principal remodeling deficit in hip fracture is specific
      to composite osteons. Hip fracture cases had zonal increases in composite osteon
      density with reduced bone formation. The data suggest that generation of
      composite osteons is a plausible mechanism leading to increasing porosity and
      trabecularization of the cortex, thus weakening the cortex in regions maximally
      loaded on fall impact.

PMID- 10913927
TI  - Supralesional and sublesional bone mineral density in spinal cord-injured
      patients.
AB  - This study was performed to evaluate supra- and sublesional bone mineral density
      (BMD) in spinal cord-injured (SCI) patients after 1 year postinjury, and to
      correlate the BMD to the neurological level; to correlate the sublesional
      demineralization to functional parameters (duration postinjury, duration of the
      initial bedrest); and to assess the role of classic methods of prevention such as
      walking or standing. Thirty-one SCI patients, all male, were studied vs. 31
      controls (age matched). The mean age of the population was 36 years (range 18-60
      years). Eleven were tetraplegic and 20 were paraplegic. Twenty-six patients
      dysplayed a complete motor lesion. The BMD was measured by dual-photon
      absorptiometry on the lumbar spine and on the femoral neck, and the bone mineral
      content (BMC) on whole-body scans. Particular attention was paid to the distal
      femur and proximal tibia upper third. Blood samples and urine samples included
      phosphocalcic parameters, with determination of urinary hydroxyproline and
      deoxypyridinoline. SCI patients showed a decrease of sublesional BMD of 41% in
      comparison with controls. This loss of bone mass is higher at the distal femur (
      52%) and proximal tibia (-70%), which are the most common sites of fracture. The
      degree of demineralization for the lumbar spine, the pelvis, and the lower limbs
      is independent of the neurological level. The duration of acute posttraumatic
      immobilization (mean 43.3 days) and the time postinjury increase the loss of bone
      mass for lower limbs (p = 0.04) and particularly for the proximal tibia (p =
      0.02). The study of biomechanical stress (i.e., standing, walking, sitting) does
      not influence the sublesional BMC. This study underlines the major role of the
      neurological lesion on the decrease of sublesional BMC in SCI patients and the
      absence of influence of biomechanical stress.

PMID- 10913928
TI  - Histomorphometric evidence for increased bone turnover without change in cortical
      thickness or porosity after 2 years of cyclical hPTH(1-34) therapy in women with
      severe osteoporosis.
AB  - Parathyroid hormone (PTH) increases trabecular but may decrease cortical bone
      mass during treatment of postmenopausal osteoporosis. In a 2-year trial, PTH,
      with or without sequential calcitonin (CT), was given to 29 osteoporotic women
      (mean age 67 +/- 7 years), in 3-month cycles [28 days hPTH(1-34), 50 microg/day,
      +/-42 days CT, 75 units/day, 20 days "free"]. Over 2 years, lumbar spine bone
      mineral density measurements increased an average of 10%. Paired iliac crest
      biopsies were obtained 28 days and 2 years after starting the trial. The addition
      of CT made no difference to changes seen with cyclical PTH alone. Thus, the
      histomorphometric analyses for all 29 treated patients were compared with a
      separate group of biopsies from untreated osteoporotic control patients (n = 15).
      No significant increments in total bone volume or trabecular architecture were
      seen over 2 years of cyclical PTH treatment, although the light microscopic
      appearance of bone was normal. At the level of the bone remodeling unit, a
      twofold increase in total trabecular erosion surface over the control
      measurements was observed within the first 28 days of PTH treatment (10 +/- 5 vs.
      5 +/- 3% trabecular surface, p < 0.01), which was sustained over 2 years.
      Trabecular bone formation rates (surface referent) were 11 +/- 7
      microm(3)/microm(2)/year in control patients and threefold higher in treated
      patients both acutely (31 +/- 31 microm(3)/microm(2)/year, p < 0.01) and after 2
      years (33 +/- 43 microm(3)/microm(2)/year, p < 0. 05). The activation frequency
      of trabecular remodeling was threefold higher than controls through 2 years of
      treatment (p < 0.05). The mean wall thickness of completed osteons after 2 years
      of treatment was significantly larger than controls (28 +/- 7 vs. 22 +/- 5
      microm, p < 0.01), suggesting a positive remodeling balance, as well as the
      histomorphometric evidence of increased bone turnover and the increased
      resorption surfaces. Over 2 years of cyclical PTH therapy, cortical thickness
      remained significantly higher than controls (680 +/- 202 vs 552 +/- 218 microm, p
      < 0.05), without significant changes in cortical porosity. Thus, the
      histomorphometric changes during cyclical PTH therapy in patients with severe
      osteoporosis are consistent with increased trabecular bone turnover and a
      positive remodeling balance, with no evidence for detrimental changes in cortical
      bone.

PMID- 10913929
TI  - Bone-muscle strength indices for the human lower leg.
AB  - This cross-sectional study is based on images from the lower leg as assessed by
      peripheral quantitative computer tomography (pQCT). Measurements were performed
      in 39 female and 38 male control subjects and 15 female professional volleyball
      players, all between 18 and 30 years of age. The images were obtained at shank
      levels of 4%, 14%, 33%, and 66% from the distal end. Bone and muscle cross
      sectional areas, and the bones' density-weighted area moment of resistance and of
      inertia were assessed. From these, muscle-bone strength indices (MBSIs) were
      developed for compression (CI = 100. bone area/muscle area) and bending (BI =
      100. bone area moment of resistance/muscle area/tibia length). Significant
      correlations between muscle cross-sectional area and bone were found at all
      section levels investigated. The strongest correlation for compression was
      observed in the sections at 14% (correlation coefficient r = 0.74), where 4.10 +/
      0.46 cm(2) bone, on average, was related to 100 cm(2) muscle. The compression
      index (CI) at the 14% level was independent of the tibia length. Interestingly,
      the 15 athletes had significantly greater CIs than the control subjects. This is
      most probably due to the greater tension development in the athletes. The highest
      correlation for bending was for anteroposterior bending at 33% of tibia length (r
      = 0.81), where the area moment of resistance, R, was on, average, 4.21 +/- 0.54
      cm(3)/100 cm(2) muscle/m tibia length. Analysis of the bones' area moment of
      inertia showed that buckling is a possible cause of bending at the 33% and 66%
      levels, but not at the 14% level. No gender differences in MBSI were found.
      Likewise, age was without significant effect. The data show that bone
      architecture depends critically on muscle cross section and tension development.
      Moreover, bone geometry (e.g., the tibia length) influences the geometrical
      distribution of bone mineral, as it was found that long bones adapted to the same
      compressive strength are wider than short ones. We conclude that MBSIs offer a
      powerful diagnostic tool for bone disorders and may contribute to improving the
      treatment of bone metabolic and other diseases.

PMID- 10913932
TI  - Erectile dysfunction: from biochemical pharmacology to advances in medical
      therapy.
AB  - Research on penile smooth muscle physiology has increased the number of drugs
      available for treating erectile dysfunction (ED). Penile erection involves the
      relaxation of smooth muscle in the corpus cavernosum. The key mediator of smooth
      muscle relaxation is nitric oxide (NO), which acts by increasing the cellular
      level of cGMP. Another cyclic nucleotide, cAMP, is involved in smooth muscle cell
      relaxation; cAMP formation is stimulated by a number of compounds, such as
      alprostadil. An increase in cAMP and/or cGMP levels can also be induced by
      inhibition of phosphodiesterases (PDEs), the enzymes involved in cyclic
      nucleotide breakdown. Both papaverine and sildenafil are PDE inhibitors.
      Papaverine is a non-specific inhibitor of these enzymes; sildenafil is an orally
      active, potent and selective inhibitor of GMP-specific PDE5, the predominant
      isoenzyme metabolizing cGMP in the cells of the corpus cavernosum. Penile smooth
      muscle contraction, induced by adrenergic fibers through alpha(1) adrenoceptors,
      produces detumescence, thus making alpha adrenoceptor antagonists suitable for
      maintenance of penile erection. The orally active drug yohimbine is a mixed
      alpha(1)-alpha(2) adrenoceptor antagonist that works by a dual mechanism; it
      facilitates sexual arousal by acting on alpha(2) adrenoceptors in the central
      nervous system and blocks adrenergic influences at peripheral level.

PMID- 10913931
TI  - [Echo-doppler monitoring of asymptomatic distal deep vein thrombosis in patients
      given low-molecular-weight-heparin at prophylactic doses after orthopedic
      surgery].

PMID- 10913933
TI  - (131)I and thyroid-associated ophthalmopathy.
AB  - OBJECTIVE: Radioiodine ((131)I) used to obtain euthyroidism in thyrotoxic
      patients is suspected of having a worsening or provoking effect on thyroid
      associated ophthalmopathy (TAO), an autoimmune disease closely related to Graves'
      disease. DESIGN: This review summarises the existing literature and describes
      risk factors influencing the course of TAO including thyroid function, cigarette
      smoking and treatment of Graves' hyperthyroidism (especially (131)I therapy).
      CONCLUSION: It is recommended that patients who may be at a greater risk of
      worsening ophthalmopathy are considered when choosing the modality of therapy of
      hyperthyroidism and also in deciding whether prophylactic systemic glucocorticoid
      treatment is indicated.

PMID- 10913934
TI  - Thyrotropin-dependent proliferation of in vitro rat thyroid cell systems.
AB  - This review is focused on the most recent knowledge on growth control of rat
      thyroid cell lines. We analyzed the effect of mitogenic as well as inhibitory
      agents, but mainly the proliferative effect elicited by thyrotropin (TSH). The
      classic cAMP-dependent protein kinase (PKA) signal transduction pathway involved
      in TSH-mediated cell growth is analyzed exhaustively. We have also reviewed new
      concepts about the participation of other effectors such as small GTPases and
      phosphatidyl inositol-3-kinase (PI3-K) and the new data about the existence of a
      cAMP-dependent but PKA-independent pathway. Finally, we give information about
      TSH induction of cell cycle-related genes, such as G1 cyclins, cyclin-dependent
      kinases (CDKs) and CDK inhibitors.

PMID- 10913935
TI  - Involvement of circulating interleukin-6 and its receptor in the development of
      euthyroid sick syndrome in patients with acute myocardial infarction.
AB  - OBJECTIVE: In patients with acute myocardial infarction (AMI), low
      triiodothyronine (T(3)) levels with normal or subnormal levels of thyrotropin
      (TSH), the euthyroid sick syndrome (ESS), have been reported, however, the
      mechanism of altered thyroid hormone metabolism is unknown. Recent reports have
      shown that interleukin-6 (IL-6) plays a key role in the pathogenesis of AMI and
      ESS. This preliminary study investigates the relationship between thyroid states
      and plasma levels of IL-6, the soluble IL-6 receptor (sIL-6R), and the soluble
      transducing 130kDa glycoprotein (sgp130) in AMI. DESIGN AND METHODS: We measured
      the concentration of TSH, free T(3) (FT(3)), free thyroxine (FT(4)), IL-6, sIL-6R
      and sgp130 in plasma from 24 patients with AMI and 20 normal controls. RESULTS:
      All 24 AMI patients showed significantly lower concentrations of FT(3) with
      normal or subnormal levels of TSH, and higher concentrations of IL-6 and sIL-6R
      than controls. IL-6 level was correlated with creatine phosphokinase (CPK) and
      FT(3) levels but not with FT(4 )or TSH levels in patients with AMI. The time
      course of IL-6 and FT(3 )concentration seemed to be closely linked. sIL-6R level
      was correlated with CPK and sgp130 levels, but not with FT(3), FT(4) or TSH
      levels. FT(4 )level was correlated with sgp130 level. CONCLUSION: Patients with
      AMI develop ESS through activation of IL-6 and its receptor system.

PMID- 10913936
TI  - Increased prevalence of thyroglobulin antibodies in Sri Lankan schoolgirls--is
      iodine the cause?
AB  - OBJECTIVE: Iodine deficiency was the likely cause of a high prevalence of goitre
      previously in Sri Lankan schoolchildren. Salt iodination was made compulsory in
      1993 but there has been no recent study, using modern techniques, of its benefits
      or harmful effects. METHODS: Three hundred and sixty-seven schoolgirls between
      the ages of 11 and 16 years had ultrasound thyroid volume, free thyroxine (T4),
      free tri-iodothyronine (T3), thyrotrophin (TSH), anti-thyroglobulin (TgAb) and
      thyroid peroxidase (TPOAb) antibodies, and urine iodine concentrations measured.
      RESULTS: Median ultrasound thyroid volume ranged from 4.8 ml (11-year-old girls)
      to 8.6 ml (16-year-old girls) with an age-related increase. Median urine iodine
      concentrations ranged from 105 to 152 microg/l. Free T4 and free T3 were normal
      in all, but TSH was elevated in four subjects (5. 53-41.29 mU/l). However, the
      prevalence of TgAb was markedly raised, ranging between 14.3% (11-year-old girls)
      and 69.7% (16-year-old girls) (P<0.03). In contrast, the prevalence of TPOAb was
      10% or less in all age groups. CONCLUSIONS: Normal median thyroid volumes, iodine
      concentrations and thyroid function would indicate that iodine deficiency is not
      a major problem in this group. The high prevalence of TgAb, hitherto unreported,
      most likely reflects excessive iodination of Tg resulting in increased
      immunogenicity. There is an urgent need to continuously monitor the adequacy and
      risks of iodination in this population.

PMID- 10913937
TI  - Silent iodine prophylaxis in Western Europe only partly corrects iodine
      deficiency; the case of Belgium.
AB  - OBJECTIVE: Belgium is one of the Western European countries in which no program
      of iodine-deficiency correction using iodized salt has been implemented, in spite
      of well-documented mild iodine deficiency. In 1995, the median urinary iodine
      concentration was 55 microg/l (normal: 100-200) and the prevalence of goiter was
      11% (normal: below 5%) in representative samples of schoolchildren aged 6-12
      years. Based on these results, the authors of the present study and others had
      emphasized to health professionals and to the public the necessity for iodine
      supplementation. The objective of this study was to evaluate as to whether these
      efforts had resulted in an improvement in the status of iodine nutrition. DESIGN:
      We performed a national survey of the status of iodine nutrition in Belgium based
      on the determination of thyroid volume, obtained by ultrasonography, and urinary
      iodine concentrations in schoolchildren. METHODS: A mobile van equipped with an
      ultrasound instrument, a computer and a deep-freeze visited 23 schools selected
      from across the country. The sample included 2855 schoolchildren (1365 boys and
      1490 girls) aged 6-12 years. RESULTS: The results show a homogeneous situation in
      the whole country, with a median urinary iodine concentration of 80 microg/l and
      a goiter prevalence of 5.7%. Urinary iodine slightly decreases with age in girls
      and reaches a critical value of 59 microg/l at the age of 12 years, together with
      a goiter prevalence of 18.4%. CONCLUSION: Iodine nutrition has improved slightly
      in Belgium but mild iodine deficiency continues, with public-health consequences.
      The improvement indicates silent iodine prophylaxis, as no official salt
      iodization measures have been taken. Silent iodine prophylaxis only partly
      corrects iodine deficiency in Western Europe. Active measures, including the
      implementation of a program of salt iodization, are urgently required.

PMID- 10913938
TI  - Serum concentrations of proinflammatory cytokines in Graves' disease: effect of
      treatment, thyroid function, ophthalmopathy and cigarette smoking.
AB  - OBJECTIVE: In the present study we have measured the concentrations of
      interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1 beta (IL-1 beta) and IL-1 receptor antagonist (IL-1Ra)
      in the serum of patients with Graves' disease (GD). By multivariate analysis, we
      have evaluated the effect of antithyroid treatment, thyroid function, the
      presence or absence of active thyroid-associated ophthalmopathy (TAO), the
      patient's smoking habits and the relation to circulating anti-thyrotropin (TSH)
      receptor (TRAb) and anti-thyroperoxidase antibodies (TPOAb). SUBJECTS: We studied
      84 GD patients, 51 untreated and 33 receiving methimazole (MMI) therapy. Twenty
      three (45%) untreated patients and 18 (54%) patients on MMI had active TAO. We
      also studied 67 normal subjects as controls. Thirty-one GD patients (43%) and 16
      controls (36%) were smokers. RESULTS: Serum IL-6 concentrations were
      significantly higher in both untreated patients (P<0.001) and treated patients
      (P<0.006), when compared with controls. Serum sIL-6R concentrations were
      significantly affected by treatment (P=0.001). Serum IL-1Ra concentrations were
      not different in GD patients, whether treated or untreated, compared with
      controls. Serum IL-6 concentrations were not influenced by thyroid function and
      there was a significant interaction between treatment and the presence of active
      TAO (P=0.003). In hyperthyroid patients with active TAO serum, sIL-6R
      concentrations were significantly higher than in those with inactive TAO
      (P=0.003). In untreated GD patients there was no significant effect of thyroid
      function and TAO activity on the serum concentrations of TNF-alpha and IL-1 beta.
      Serum IL-1Ra concentrations were not affected by the presence of TAO. Smoking had
      no effect on serum IL-6, sIL-6R, TNF-alpha, IL-1 beta and IL-1Ra concentrations,
      even in the presence of an active TAO. Serum concentrations of IL-6, sIL-6R, TNF
      alpha and IL-1 beta and IL-1Ra were not different in patients with and without
      TRAb or TPOAb, in relation to either thyroid function, TAO activity or smoking.
      CONCLUSIONS: Our work shows that: (i) the proinflammatory cytokine pattern in GD
      is greatly influenced by antithyroid drug treatment; (ii) the increased
      circulating IL-6/sIL-6R concentrations observed in patients with active TAO may
      derive from the activation of humoral reactions in sites other than the thyroid;
      and, (iii) cigarette smoking has no effect on serum IL-1/IL-1Ra concentrations in
      TAO.

PMID- 10913940
TI  - Serum concentrations of LH and FSH in the healthy newborn.
AB  - OBJECTIVE: A sex difference in fetal and neonatal pituitary-gonadal function has
      been well documented. The aim of the following study was to determine sex
      differences and patterns of basal LH/FSH in the neonatal period. DESIGN:
      Peripheral venous blood was obtained from 164 healthy full term newborns (91
      males, 73 females) for clinically indicated laboratory examinations. RESULTS: In
      male newborns, LH values were initially low (days 1-5), increased between days 6
      and 10, and reached maximum levels between days 16 and 20. Levels of FSH were
      initially low (days 1-5), increased between days 6 and 10 and reached maximum
      levels between days 11 and 15. In female newborns, LH levels were generally lower
      than in newborn boys; levels were initially low, then increased between days 11
      and 15 and reached maximum levels at the end of the newborn period. FSH values
      were generally higher than in newborn boys; there were initially low values with
      a first peak between days 11 and 15 and a second peak between days 21 and 28.
      CONCLUSIONS: LH values in male newborns were higher and exceeded values in female
      newborns, whereas FSH values in female newborns exceeded male newborn values.
      Male newborns do not exhibit any peaks of LH and FSH activity, whereas female
      newborns exhibit two FSH peaks during this period.

PMID- 10913939
TI  - Effects of acute infusion of erythropoietin on paradoxical responses of growth
      hormone to thyrotropin-releasing hormone in acromegalic patients.
AB  - OBJECTIVE: Our aim has been to evaluate the effects of i.v. infusion of
      recombinant human erythropoietin (rhEPO) on the responses of growth hormone (GH),
      prolactin (PRL) and thyrotropin (TSH) to thyrotropin-releasing hormone (TRH)
      stimulation in acromegalic patients. METHODS: We studied 16 patients (8 females,
      aged 29-68 years) with active acromegaly and 12 control subjects (7 females, 24
      65 years). All participants were tested with TRH (400 microg i.v. as bolus) and
      with TRH plus rhEPO (40 U/kg at a constant infusion rate for 30 min, starting 15
      min before TRH injection) on different days. Blood samples were obtained between 
      30 and 120 min for GH and PRL determinations, and between -30 and 90 min for TSH
      determinations. Hormone responses were studied by a time-averaged (area under the
      secretory curve (AUC)) and time-independent (peak values) analysis. RESULTS:
      Twelve patients exhibited a paradoxical GH reaction after TRH administration with
      great interindividual variability in GH levels. When patients were stimulated
      with rhEPO plus TRH there were no changes in the variability of GH responses or
      in the peak and AUC for GH secretion. Infusion with rhEPO did not induce any
      significant change in GH secretion in normal subjects. Baseline and TRH
      stimulated PRL concentrations in patients did not differ from those values found
      in controls. When TRH was injected during the rhEPO infusion, a significant
      (P<0.05) increase in PRL concentrations at 15-120 min was found in acromegalic
      patients. Accordingly, the PRL peak and the AUC for PRL secretion were
      significantly increased in patients. Infusion with rhEPO had no effect on TRH
      induced PRL release in control subjects. Baseline TSH concentrations, as well as
      the TSH peak and the AUC after TRH, were significantly lower in patients than in
      controls. Infusion with rhEPO modified neither the peak TSH reached nor the AUC
      for TSH secretion after TRH injection in acromegalic patients and in healthy
      volunteers. CONCLUSION: Results in patients with acromegaly suggest that (i) the
      paradoxical GH response to TRH is not modified by rhEPO infusion, (ii) rhEPO has
      no effect on TRH-induced TSH release, and (iii) acute rhEPO administration
      increases the TRH-induced PRL release in acromegalic patients.

PMID- 10913941
TI  - Influence of androgens and age on androgen receptor and 5 alpha-reductase II
      transcription.
AB  - OBJECTIVE: The regulation of the androgen receptor (AR) and 5 alpha-reductase II
      (5RII) gene in genital skin fibroblasts is of particular interest in
      understanding androgen-dependent embryonic formation of external male genitalia.
      DESIGN: Human genital skin fibroblasts from pre- and postpubertal male
      individuals (aged 5 months to 51 years) were incubated with testosterone and
      dihydrotestosterone under various conditions to study the regulation of AR and
      5RII transcript concentrations dependent on androgen concentration and donor age.
      METHODS: A competitive reverse transcribed PCR (RT-PCR) protocol was designed to
      achieve simultaneous relative quantification (semi-quantification) of AR and 5RII
      mRNAs in standardized whole RNA samples from each donor. RESULTS: Concentrations
      of AR and 5RII mRNAs are not influenced by androgens in genital skin fibroblasts.
      Moreover, comparison of AR transcript concentrations in genital skin fibroblast
      cell lines revealed weak variations independent of donor age, while 5RII
      transcription exhibited clear individual differences with a declining tendency
      towards higher ages. CONCLUSIONS: The transcription of AR and 5RII is not
      directly regulated by testosterone or dihydrotestosterone in pre- or postpubertal
      human genital skin fibroblasts. However, donor age seems to play a role in
      gradual depression of 5RII transcription.

PMID- 10913942
TI  - Usefulness of the desmopressin test in the postoperative evaluation of patients
      with Cushing's disease.
AB  - OBJECTIVE: To evaluate the plasma ACTH and serum cortisol responses to
      desmopressin in patients with Cushing's disease either before or after pituitary
      adenomectomy during long-term follow-up, and to compare the results with those
      obtained after corticotrophin-releasing hormone (CRH) testing. DESIGN: Plasma
      ACTH and serum cortisol concentrations were evaluated after the administration of
      desmopressin (10 microg i.v.) or CRH (1 microg/kg i. v.) in 34 patients with
      Cushing's disease. Twenty-four patients with active Cushing's disease were
      evaluated both before and after transsphenoidal pituitary surgery (TSS); these
      patients were followed up for 1-36 months. Ten patients were studied only after a
      long-term period (1-19 years, median 4 years) after TSS (six patients), TSS plus
      external pituitary irradiation (three patients) and TSS plus radiosurgery (one
      patient). RESULTS: In 24 patients with active Cushing's disease a significant
      ACTH/cortisol response (P<0.001) was induced by either desmopressin (ACTH from a
      baseline of 15.3+/-2.7 pmol/l to a peak of 40.9+/-7.3 pmol/l; cortisol from 673+/
      59 nmol/l to 1171+/-90 nmol/l) or CRH (ACTH from a basal of 14. 2+/-2.5 pmol/l to
      a peak of 47.2+/-7.7 pmol/l; cortisol from 672+/-50 nmol/l to 1192+/- 80 nmol/l).
      In all patients a positive cortisol response to desmopressin was found. After
      pituitary adenomectomy the 14 'cured' patients were followed up for 1-36 months;
      desmopressin administration never induced ACTH or cortisol responsiveness in any
      patient. In contrast, a progressive recovery of ACTH and cortisol responses after
      CRH was observed at different intervals of time in all patients but one. Five
      patients, in whom the cortisol concentration only normalized after surgery,
      showed a persistent responsiveness to desmopressin, and two of them relapsed 12
      and 24 months later. In five patients who were not cured, the hormonal
      responsiveness to either CRH or desmopressin was similar before and after
      operation. Of 10 patients studied only after long-term follow-up, six were cured
      and a normal response to CRH was present, whereas no changes in ACTH/cortisol
      concentrations were induced by desmopressin. The other four unsuccessfully
      operated patients underwent pituitary irradiation and showed different and
      equivocal hormonal responses to desmopressin and to CRH. CONCLUSIONS: During the
      postoperative follow-up of patients with Cushing's disease, the maintenance or
      the disappearance of the hormonal response may be related to the persistence or
      the complete removal of adenomatous corticotrophs, respectively. It is suggested
      that desmopressin test should be performed in the preoperative evaluation and
      follow-up of patients with ACTH-dependent Cushing's syndrome.

PMID- 10913943
TI  - Plasma soluble tumor necrosis factor-alpha receptors circulate in proportion to
      leptin levels during the menstrual cycle in lean but not in obese women.
AB  - OBJECTIVE: In recent studies serum leptin levels were significantly higher in the
      luteal phase than in the follicular phase, but the mechanism of changing leptin
      levels are unknown. Several research lines indicate a potential role for tumor
      necrosis factor (TNF-alpha) in ovulation and reproductive events. As TNF-alpha
      appears to regulate leptin secretion, we speculated that TNF-alpha might be
      involved in leptin variations during the menstrual cycle. DESIGN AND METHODS:
      Nine healthy never obese and ten overweight normally cycling women were studied.
      TNF-alpha action - through the plasma levels of the soluble fraction of the tumor
      necrosis factor receptors 1 and 2 (sTNFR1 and sTNFR2) - and leptin concentrations
      were measured in the follicular (F), peri-ovulatory (PO) and luteal phases (L) of
      their menstrual cycles. RESULTS: Circulating leptin levels were significantly
      associated with the stage of the menstrual cycle (P<0.001), being higher in PO
      and L phases. However, only three of ten overweight subjects vs eight of nine
      lean women (Chi square P=0.014 after Fisher's exact test) showed significantly
      higher leptin levels in the PO and L than in the F phase (95% confidence interval
      (95% CI) of the differences, 3.7 to 10.2 ng/ml, paired t-test P=0.001). In these
      women (group 1), the changes in leptin levels parallelled the variations observed
      in plasma sTNFR1 (2.50+/-0.1 vs 2.11+/-0.05 ng/ml, P<0.0001, 95% CI, 0.21 to
      0.56) and sTNFR2 levels (5.19+/-0.28 vs 4.55+/-0.25 ng/ml, P<0.0001, 95% CI, 0.
      47 to 0.81). In the remaining women (group 2), leptin (95% CI, -1 to 9.2 ng/ml,
      P=not significant (NS)), sTNFR1 (95% CI, -0.3 to 0.14 ng/ml, P=NS) and sTNFR2
      levels (95% CI, -0.95 to 0.39 ng/ml, P=NS) were essentially unaltered throughout
      the menstrual cycle. Group 2 women were similar in age (36.1+/-2.9 vs 37.3+/-1.4
      years) and significantly overweight (body mass index 31+/-2.9 vs 23.9+/-1. 2
      kg/m(2)) compared with group 1 women. A negative correlation was observed between
      leptin levels in the follicular phase and the change in plasma leptin from F to L
      phase in all subjects (r=-0.67, P=0.002). CONCLUSIONS: Circulating leptin and
      sTNFRs levels change significantly during the menstrual cycle of most lean women.
      In contrast, the levels of these molecules remain essentially unaltered during
      the F, PO and L phases in the majority of overweight women. Obesity might be
      associated not only with blunted diurnal excursions and dampened pulsatility, but
      also with blunted excursions during the menstrual cycle.

PMID- 10913944
TI  - Anthropometric parameters and their relationship to serum growth hormone-binding
      protein and leptin levels in children with acute lymphoblastic leukemia: a
      prospective study.
AB  - OBJECTIVE: The aim of this study was to follow auxological parameters and their
      relationship to serum growth hormone-binding protein (GHBP) and leptin levels in
      children with acute lymphoblastic leukemia (ALL). DESIGN AND METHODS: In total,
      26 prepubertal children with ALL were studied. We report these data at the time
      of the clinical diagnosis (n=26) and at 6 (n=21), 12 (n=21), 18 (n=21), 24
      (n=20), 30 (n=16) and 36 months (n=16) after beginning treatment. RESULTS: Serum
      GHBP levels decreased during the first 18 months and returned to normal when
      therapy was withdrawn. Height SDS increased at 24 months after diagnosis. Weight
      and the upper arm circumference had increased 6 months after chemotherapy
      withdrawal, whereas tricipital and subscapular skinfolds had increased both at 6
      months after diagnosis and 6 months after therapy had stopped. Therefore, the
      tendency to become overweight is both an early and a late side-effect of anti
      leukemia therapy. A significant positive correlation was found between serum
      leptin levels and every nutritional anthropometric parameter, with body mass
      index having the best relationship. However, serum GHBP levels were only
      correlated with BMI at the end of the study. No correlation was found between
      leptin and GHBP. CONCLUSIONS: In children with ALL, linear growth is compromised
      during the acute phase of their illness and therapy; this is probably secondary
      to a state of partial and transient GH insensitivity. These patients tend to
      become obese after therapy withdrawal, with leptin being an excellent nutritional
      marker.

PMID- 10913945
TI  - Hyperproinsulinemia is not a characteristic feature in the offspring of patients
      with different phenotypes of type II diabetes.
AB  - OBJECTIVE: The purpose of this work was to study whether there are differences in
      plasma proinsulin levels and proinsulin-to-specific insulin ratio in the
      offspring of patients with different phenotypes of type II diabetes. DESIGN:
      Eleven glucose-tolerant offspring of type II diabetic patients with deficient
      insulin secretion phenotype (IS group), nine glucose-tolerant offspring of
      patients with insulin-resistant phenotype (IR group), and fourteen healthy
      control subjects without a family history of diabetes were studied. METHODS:
      Plasma specific insulin, plasma proinsulin, and plasma C-peptide levels were
      measured during a 2-h oral glucose tolerance test and during hyperglycemic clamp.
      RESULTS: Plasma proinsulin levels during the oral glucose tolerance test and the
      hyperglycemic clamp did not differ among the study groups. The IR group had a
      lower fasting plasma proinsulin-to-specific insulin ratio (10.3+/-1.7%) than the
      control group (15.4+/-1.4%; P<0.05) and the IS group (18.6+/-2.7%; P<0.05).
      Furthermore, the IR group had lower plasma proinsulin-to-specific insulin ratio
      at 30, 60 and 90 min after the oral glucose load than the IS group. However,
      there were no significant differences in proinsulin-to-C-peptide ratio during the
      oral glucose tolerance test among the study groups. In stepwise multiple
      regression analysis, hepatic specific insulin extraction in the fasting state
      (beta =0.65; P<0.001) and fasting blood glucose (beta =0.32; P<0.05) together
      explained 52% of the variation in fasting plasma proinsulin-to-specific insulin
      ratio. CONCLUSIONS: Hyperproinsulinemia is not a characteristic finding in
      glucose-tolerant offspring of type II diabetic probands with deficient insulin
      secretion or insulin-resistant phenotype. The differences in proinsulin-to
      specific insulin ratios were most likely explained by different hepatic
      extraction among the study groups.

PMID- 10913946
TI  - The Sp1 binding site polymorphism in the collagen type I alpha 1 (COLIA1) gene is
      not associated with bone mineral density in healthy children, adolescents, and
      young adults.
AB  - Up to 85% of the variance in bone mineral density (BMD) is genetically
      determined. A putative candidate gene involved in the regulation of bone mass is
      the COLIA1 gene encoding type I collagen, which is the major protein of bone. We
      examined possible allelic influences of a G to T COLIA1 gene polymorphism in a
      recognition site for the transcription factor Sp1 on: (i) gain of forearm BMD
      using single photon absorptiometry (SPA); and (ii), BMD of the forearm, spine,
      hip, and whole body with dual X-ray absorptiometry (DXA). At baseline, 269
      healthy boys and girls aged 8.2-16.5 years were eligible for the study. Forearm
      BMD measurements obtained at baseline and after 3.8+/-0.1 years (+/-s.d.) were
      used to calculate the annual percentage change in BMD. Calcium intake and
      physical activity were determined by a detailed questionnaire at baseline and
      after 1 year. Essentially no significant differences in forearm BMD gain or in
      BMD assessed at the forearm, spine, and whole body were observed among the three
      COLIA1 genotypes. In conclusion, the data indicate that the polymorphism at the
      Sp1 site in the COLIA1 gene is not associated with BMD or gain of forearm BMD in
      healthy boys and girls.

PMID- 10913947
TI  - Structural organization and chromosomal localization of the human type II
      deiodinase gene.
AB  - OBJECTIVE: The selenoenzyme type 2 iodothyronine 5' deiodinase (DII) catalyzes
      the conversion of thyroxine into its active form tri-iodothyronine (T3),
      modulating thyroid hormone homeostasis in a local, tissue-specific manner. The
      amphibian, rodent and human cDNAs encoding this enzyme have been recently cloned
      and expressed. At present, little information regarding the genomic structure of
      mammalian DII is available. DESIGN AND METHODS: The complete structure, including
      intron-exon junctions, of the human DII (hDII) gene was obtained by long PCR and
      rapid amplification of cDNA ends (RACE). Chromosomal assignment of the hDII gene
      was performed by fluorescence in situ hybridization using a highly specific
      probe. RESULTS AND CONCLUSIONS: Our data demonstrated that hDII is a single copy
      gene located on chromosome 14, position 14q24.3. The gene spans over 15 kb, and
      the 7 kb transcript is encoded by three exons of 149 bp, 273 bp and 6.6 kb
      separated respectively by two 274 bp and 7.4 kb introns. A restriction map of the
      hDII gene is also reported. These data will help in further studies of the role
      of DII in the maintenance of peripheral thyroid hormone homeostasis.

PMID- 10913948
TI  - The in vivo effects of beta-3-receptor agonist CGP-12177 on thyroxine
      deiodination in cold-exposed, sympathectomized rat brown fat.
AB  - OBJECTIVE: The effects of the beta-3-receptor agonist CGP-12177 on thyroxine (T4)
      deiodination in sympathectomized (SX) interscapular brown adipose tissue (BAT)
      were assessed in 300 g body weight (BW) Wistar rats. DESIGN: Seven days after SX,
      groups of rats were implanted s.c. with pellets containing 5mg CGP-12177 or 5mg
      norepinephrine (NE) and were immediately placed at 4 degrees C for 24h. Other SX
      groups were injected with CGP-12177 or NE 1mg/kg BW i. p. and placed in the cold
      for 4h. The latter group was injected, in addition, with prazosin 0.4 mg/100g BW
      i.p. or propranolol 0.5mg/100g BW i.p. 15 min before and 2h after the
      administration of CGP-12177 or NE. METHODS: Two hours after the last injection of
      prazosin or propranolol, animals were killed and BAT was removed, homogenized and
      centrifuged at 500 g for 10 min at 4 degrees C. The infranatants were incubated
      during 60 min in the presence of dithiothreitol and 1 microCi [(125)I]T4.
      Aliquots were chromatographed on paper for the measurement of [(125)I]T4 and its
      deiodinated subproducts. RESULTS: CGP-12177 restored normal T4 deiodination in SX
      BAT from both groups, but NE was slightly more effective. Propranolol, although
      not prazosin, blocked the CGP-12177 effects. Contrariwise, the NE-induced rise in
      deiodination was blocked by prazosin and to a lesser extent by propranolol.
      CONCLUSIONS: The results indicate that CGP-12177 stimulated the in vivo
      activation of 5'-deiodinase type II activity predominantly via beta-3-receptor,
      without participation of alpha-1-receptors.

PMID- 10913951
TI  - Guest editorial

PMID- 10913950
TI  - Downregulation of long-form prolactin receptor mRNA during prolactin-induced
      luteal regression.
AB  - OBJECTIVE: Prolactin is capable of both trophic and lytic actions in rat corpora
      lutea. In corpora lutea responding to a trophic prolactin signal, the long form
      of the prolactin receptor is the dominant form and is upregulated by prolactin.
      We investigated whether mRNA for the short form of the prolactin receptor was
      dominant in corpora lutea responding to a lytic prolactin signal, and whether the
      relative concentrations of the mRNAs for both forms of the prolactin receptor
      were changed during this response. DESIGN AND METHODS: Immature rats were
      ovulated by injection of 5 IU equine chorionic gonadotrophin and 5 IU human
      chorionic gonadotrophin, and were hypophysectomized shortly after ovulation. Nine
      days after hypophysectomy, rats were injected with prolactin (500 microg/day) or
      vehicle for 24 (n=6, n=6) or 72 h (n=13, n=5). Total RNA was isolated from
      corpora lutea and mRNA for both types of prolactin receptor were analyzed by
      semiquantitative RT-PCR using the ribosomal protein S16 as the internal control.
      RESULTS: The intensities of the long- and short-form prolactin receptor signals
      were normalized to the S16 internal control and expressed as relative
      densitometric units. The normalized values at 24h for prolactin-treated vs
      vehicle-treated rats were 0.23 +/- 0.05 vs 0.49 +/- 0.15 (P>0.05) for the short
      form and 4.04 +/- 0.8 vs 4.23 +/- 0. 6 (P>0.05) for the long form. The values for
      72 h were 0.30 +/- 0.05 vs 0.24 +/- 0.05 (P>0.05) for the short form and 2.76 +/-
      0.4 vs 5. 53 +/- 0.3 (P<0.01) for the long form respectively. CONCLUSION: The
      long form of the prolactin receptor is the dominant form at both time-points;
      however, the concentration of mRNA for this receptor isoform was specifically
      downregulated by prolactin treatment. Our results suggest that the short form of
      the prolactin receptor alone is unlikely to mediate the luteolytic action of
      prolactin, but that luteolytic events may be influenced via a change in the ratio
      of the two receptor isoforms.

PMID- 10913949
TI  - Role of phosphodiesterase and protein kinase G on nitric oxide-induced inhibition
      of prolactin release from the rat anterior pituitary.
AB  - OBJECTIVE: In order to determine the mechanism by which nitric oxide (NO)
      inhibits prolactin release, we investigated the participation of cGMP-dependent
      cAMP-phosphodiesterases (PDEs) and protein kinase G (PKG) in this effect of NO.
      METHODS: Anterior pituitary glands of male rats were incubated with inhibitors of
      PDE and PKG with or without sodium nitroprusside (NP). Prolactin release, and
      cAMP and cGMP concentrations were determined by RIA. RESULTS AND CONCLUSIONS: The
      inhibitory effect of NP (0.5 mmol/l) on prolactin release and cAMP concentration
      was blocked by EHNA (10(-4)mol/l) and HL-725 (10(-4)mol/l), inhibitors of cGMP
      stimulated cAMP-PDE (PDE2). 8-Br-cGMP (10(-4) and 10(-3)mol/l), which mimics cGMP
      as a mediator of NP effects on prolactin release, also decreased cAMP
      concentration. Zaprinast (10(-4)mol/l), a selective inhibitor of specific cGMP
      PDE (PDE5), potentiated the NP effect on cAMP concentration. Rp-8-[(4
      chlorophenyl)thio]-cGMP triethylamine (Rp-8-cGMP, 10(-7)-10(-6)mol/l), an
      inhibitor of PKG, reversed the effect of NP on prolactin release. The present
      study suggests that several mechanisms are involved in the inhibitory effect of
      NO on prolactin release. The activation of PDE2 by cGMP may mediate the
      inhibitory effect of NO on cAMP concentration and therefore on prolactin release.
      NO-activated PKG may also be participating in the inhibitory effect of NO on
      prolactin release.

PMID- 10913952
TI  - The critical and expanding role of genetics in assisted reproduction.
AB  - With the progress of the human gene mapping initiative, it is expected that the
      entire genome will be mapped within two years. A significant use for these data
      will centre on testing for genetic disease. Professionals associated with
      assisted reproduction are presented with a very special subset of the population,
      namely, couples suffering from infertility. Infertility may occur in the male,
      the female or both partners and may be heritable. Infertility, subfertility or
      recurrent spontaneous miscarriage is associated with chromosomal or genetic
      anomalies, suggesting that basic developmental genetics should be a part of the
      education of the physician or clinical embryologist. A review of the most common
      infertility-associated chromosomal and genetic diseases for which genetic testing
      has become routine in infertile parents and in the products of assisted
      reproduction through preimplantation genetic diagnosis (PGD) and prenatal testing
      follows. Less common genetic diseases that have compromising effects on
      reproduction and which are likely to be encountered by providers of assisted
      reproduction are also considered.

PMID- 10913953
TI  - FISH analysis on day 5 post-insemination of human arrested and blastocyst stage
      embryos.
AB  - Preimplantation genetic diagnosis (PGD) is usually performed on cleavage stage
      embryos on day 3 post-insemination. Fluorescent in situ hybridization (FISH) has
      revealed four groups of chromosome patterns in embryos at this stage: uniformly
      normal, uniformly abnormal, mosaic and chaotic. Recently, some in vitro
      fertilization (IVF) clinics have started to perform blastocyst stage transfer. In
      blastocysts, conventional karyotyping has shown that all four groups of
      chromosome patterns are observed. In the present study, embryos were cultured to
      day 5 and were subject to a two-round multicolour FISH procedure for chromosome
      analysis to ensure almost every nucleus was examined. Probes for chromosomes X, Y
      and 18 were used in the first round and those for chromosomes 13 and 21 in the
      second round. Twenty arrested embryos (274 cells) and 19 blastocyst stage embryos
      (1272 cells) were analysed. Four arrested embryos and two blastocysts were
      uniformly diploid. The remaining 33 embryos were mosaic, including 17
      blastocysts. Most of the blastocysts had a high proportion of diploid cells while
      in the arrested embryos, this proportion varied widely. For PGD, this high
      prevalence of mosaicism persisting to the blastocyst stage may pose problems
      similar to mosaicism in cleavage stage embryos.

PMID- 10913954
TI  - Recurrent triploidy of maternal origin.
AB  - We report the occurrence of triploid preimplantation embryos following in vitro
      fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a woman with
      two previously-identified triploid conceptuses which spontaneously underwent
      fetal demise at 10 and 23 weeks' gestation. An error in maternal meiosis II is
      proposed as the most likely cause.

PMID- 10913956
TI  - The situation of preimplantation genetic diagnosis in Germany: legal and ethical
      problems.
AB  - Preimplantation genetic diagnosis (PGD) has not been performed in Germany.
      Existing German laws do not explicitly permit or prohibit PGD. German law does
      forbid the wasting of totipotent embryonic cells, fertilizing oocyctes without
      transferring them in the same cycle, and the use of micromanipulations that later
      may harm embryonic development. German law also limits the number of oocytes
      allowed to be fertilized in each in vitro fertilization (IVF) cycle to three and
      prohibits research on embryos. The existence of these laws may impede but not
      prevent the development of PGD programmes in Germany. In contrast, the liberal
      regulation of pregnancy termination coupled with the development of ethical
      guidelines specific to PGD may facilitate the introduction of PGD in Germany.
      Because of these contradictions, legislation is required to clarify the legal
      status of PGD in Germany.

PMID- 10913955
TI  - The decision to cancel a preimplantation genetic diagnosis cycle.
AB  - It has been suggested that a minimum number (six) of cumulus-oocyte complexes
      (COCs) should be retrieved for fertilization to offer enough chances to ensure a
      pregnancy after a preimplantation genetic diagnosis (PGD) procedure. Therefore a
      decision to cancel a PGD cycle should be adequately weighted to offer the
      patients the highest chances to obtain a pregnancy. We describe a case where,
      after retrieving only three COCs suitable for fertilization, a triplet pregnancy
      was obtained. This case suggests that, although low numbers of COCs can reduce
      the effectiveness of the PGD procedure, other factors are involved in its final
      result. Thus, the opportunity of routinely cancelling such cycles should be
      reconsidered. In addition, this is, to our knowledge, the first case where sex
      selection was carried out to prevent the birth of carriers of the abnormal gene,
      and not of affected offspring.

PMID- 10913958
TI  - Selection of the most common chromosome abnormalities in oocytes prior to ICSI.
AB  - So far, all preimplantation genetic diagnosis (PGD) protocols in use produce
      results after the eggs have been fertilized. However, these approaches are not
      acceptable for patients with moral objections to the generation and discard of
      supernumerary zygotes or embryos. In these circumstances, only those oocytes to
      be replaced may be inseminated. The purpose of this study was to develop a PGD
      protocol to diagnose first polar bodies (PBs) prior to Intracytoplasmatic Sperm
      Injection (ICSI) in order to inseminate only those oocytes found to be
      chromosomally normal. PB biopsy was performed 1 hour after ovum pick up, and
      after fixation, the PBs were analysed by FISH and the eggs inseminated by ICSI no
      later than 7 hours after retrieval. One third (33.3%) of the PBs were aneuploid.
      Fifty-four normal and 12 non-resolved oocytes were injected by ICSI, of which 65%
      became 2-PN zygotes. Embryo transfer on day 2 was possible in all 10 patients
      (average maternal age 35.2+/-3.2, range 29-39 years), of which 6 became pregnant
      with 8 fetuses (28.6% or 8/28 transferred embryos). The results indicate that PB
      analysis of some common chromosome abnormalities is feasible within time limits
      imposed by ICSI insemination (6 hours or less).

PMID- 10913957
TI  - Clinical application of preimplantation genetic diagnosis for cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disease characterized by
      obstruction and chronic infections of the respiratory tract and pancreatic
      insufficiency. The gene was cloned in 1989 and the most frequent mutation was
      shown to be the delta F508 mutation. During PGD, embryos obtained in vitro are
      checked for the presence or absence of the mutation, after which only embryos
      shown to be free of the mutation are returned to the mother. Up to 1999, 48
      intracytoplasmic sperm injection (ICSI) and in vitro fertilization (IVF) cycles
      had been carried out for PGD for CF in 24 couples, and different diagnostic tests
      had been used to select non-affected embryos. Thirteen patients became pregnant
      and 12 healthy babies have been born.

PMID- 10913959
TI  - Clinical pregnancy following blastomere biopsy and PGD for a reciprocal
      translocation carrier: analysis of meiotic outcomes and embryo quality in two IVF
      cycles.
AB  - A couple were referred for preimplantation genetic diagnosis (PGD) following
      diagnosis of a reciprocal translocation in the female partner:
      46,XX,t(14;22)(q11.2;q13.3). PGD was carried out using fluorescence in situ
      hybridization (FISH) with probes specific for the translocated and centric
      segments of chromosome 22. An initial cycle was unsuccessful, producing 11
      embryos for biopsy, only one of which, when followed up on day 4, yielded more
      than 10 nuclei (median 7.5, n=10). In addition, five of the embryos showed mosaic
      or chaotic chromosome constitutions; some of these embryos had fragmented or
      multilobed abnormal nuclei, hindering interpretation of the FISH signals. The
      single embryo transferred did not result in a pregnancy. A second cycle, using a
      revised protocol, produced 10 embryos, three of which were transferred, resulting
      in an ongoing singleton pregnancy. All the remaining embryos yielded 12 to 23
      nuclei by day 4 (median 17, n=7). Apart from some tetraploid nuclei, only one
      embryo showed mosaicism. The significance of the changes in protocol leading to
      the successful outcome is discussed, and the pattern of meiotic segregation
      products is analysed and compared with other previous reports of reciprocal
      translocations.

PMID- 10913960
TI  - A successful strategy for preimplantation diagnosis of medium-chain acyl-CoA
      dehydrogenase (MCAD) deficiency.
AB  - Preimplantation genetic diagnosis (PGD) involves the screening of biopsied cells
      from in vitro fertilization (IVF) generated embryos. This procedure allows the
      selective transfer of unaffected embryos and thus may be preferable to prenatal
      diagnosis for couples at high risk of transmitting genetic defects to their
      offspring. In this way, termination of pregnancy is avoided. We describe here the
      development and first clinical application of PGD for medium-chain acyl-CoA
      dehydrogenase deficiency (MCAD). MCAD is a common inherited metabolic disorder
      affecting fatty acid beta oxidation. The condition is autosomal recessive with an
      incidence of 1/6000-1/15 000 live births in the UK. It presents usually within
      the first two years of life with fasting-associated hypoketotic hypoglycaemia
      which may lead to coma and death. The strategy developed was based on multiplex
      fluorescent PCR, and adapted for single cell detection. Mutation analysis was
      carried out using single-strand conformation polymorphism (SSCP) with fluorescent
      detection. The embryos generated through IVF arrested on day two post
      insemination and consequently none were available for transfer; all available
      blastomeres were used to confirm the accuracy and reliability of the diagnostic
      assays.

PMID- 10913962
TI  - Current awareness
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of prenatal diagnosis. Each bibliography is divided into 17 sections: 1 Books,
      Reviews & Symposia; 2 General Interest; 3 Normal Fetal Development; 4
      Gametogenesis and Pre-implantation Diagnosis; 5 First Trimester Diagnosis; 6
      Second Trimester Diagnosis; 7 Fetal Diagnosis by Ultrasound and Other Imaging; 8
      Maternal Screening; 9 Screening for Carriers of Genetic Abnormality; 10
      Technological Developments; 11 Confined Placental Mosaicism and Uniparental
      Disomy; 12 Molecular Cytogenetics; 13 Fetal Cells in Maternal Circulation; 14
      Fetal Therapy; 15 Psychosocial Aspects; 16 Epidemiology and Environmental
      Factors; 17 Developmental Pathology. 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- 10913961
TI  - Analysis of chromosome abnormalities in sperm and embryos from two
      45,XY,t(13;14)(q10;q10) carriers.
AB  - Robertsonian translocation t(13q14q) is studied in sperm and embryos of two
      couples undergoing preimplantation genetic diagnosis (PGD) in which both males
      are carriers of the translocation. It is already known that the chances of
      achieving pregnancy for a translocation carrier are directly linked to the number
      of normal or balanced embryos available for replacement. In our work it was found
      that the frequency of balanced spermatozoa was almost identical in both patients
      (74 and 77%), and after PGD, the frequencies of abnormal embryos caused by the
      translocation were also similar. Sperm chromosome analysis in translocation
      carriers can provide a reasonable basis for estimating a baseline of chromosome
      abnormalities to be found in embryos during an assisted reproductive cycle.
      However, individual factors not linked to the translocation can also produce
      other chromosome abnormalities (mosaicism, haploidy, polyploidy) and may
      compromise the chances of achieving a viable pregnancy.

PMID- 10913963
TI  - Defining functional domains within PF16: a central apparatus component required
      for flagellar motility.
AB  - Mutations affecting the assembly and stability of the central apparatus result in
      flagellar paralysis. Chlamydomonas cells with mutations at the PF16 locus have
      paralyzed flagella, and the C1 microtubule of the central apparatus is missing in
      isolated axonemes. On the basis of its mutant phenotype, sequence, and
      localization, PF16, a member of the armadillo repeat containing family of
      proteins, is involved in protein-protein interactions required for stability of
      the C1 microtubule and flagellar motility. Previous biochemical analysis of
      flagella isolated from pf16 cells demonstrated that assembly of the PF16 protein
      is either dependent on, or required for, the assembly of at least two other
      flagellar components. As a first step toward identifying functional domains in
      the PF16 protein that are essential for these interactions, we have characterized
      three mutations at the PF16 locus. In addition, we have generated deletion
      constructs of the PF16 gene and tested for their ability to assemble and rescue
      motility upon transformation of mutant pf16 cells. Our results demonstrate that
      the first armadillo repeat is necessary but not sufficient for assembly; that the
      C-122 amino acids are not required for assembly or motility; and that the repeats
      appear to form a single functional unit required for PF16 assembly.

PMID- 10913964
TI  - The single neurofilament subunit of the lamprey forms filaments and regulates
      axonal caliber and neuronal size in vivo.
AB  - Neurofilaments (NFs) are composed of a heteropolymer of three related subunits in
      mammalian neurons, where they are a major component of the cytoskeleton in large
      neurons and are thought to regulate axonal diameter. NFs in the lamprey, while
      ultrastructurally and functionally indistinguishable from mammalian NFs, are
      polymers of a single subunit protein, NF180. In this study, we use the simplicity
      of lamprey NFs and the accessibility of the lamprey central nervous system (CNS)
      to examine the effects of overproducing NFs in an identified giant neuron in
      vivo, and thus to elucidate the role of NFs in regulating neuronal size and
      axonal caliber in the vertebrate CNS. We show that overexpression of NF180 tagged
      with a variant of Green Fluorescent Protein (EYFP) in identified lamprey neurons
      (ABCs) and in human neuroblastoma (NB2a) cells results in the assembly of
      exogenous NF180 into ultrastructurally normal NFs that are tightly packed and
      unphosphorylated. These accumulate in the somata of NB2a cells and produce
      somatic swelling by 3 days post-transfection. NF180 overexpression in lamprey
      ABCs in vivo causes exogenous NFs to accumulate in ABC axons, somata, and
      dendrites, and induces a significant increase in axonal diameter without
      increasing axonal NF packing density. Overexpression of EYFP alone has none of
      these effects. We conclude that NF180 normally plays a critical role in
      determining axonal caliber in ABCs and may influence neuronal size in situations
      where NFs accumulate in the soma, such as after axonal injury.

PMID- 10913966
TI  - Vigorous beating of Chlamydomonas axonemes lacking central pair/radial spoke
      structures in the presence of salts and organic compounds.
AB  - Flagella of Chlamydomonas mutants lacking the central pair of microtubules or
      radial spokes do not beat; however, axonemes isolated from these mutants were
      found to display vigorous bending movements in the presence of ATP and various
      salts, sugars, alcohols, and other organic compounds. For example, about 15% of
      the total axonemes isolated from pf18, a mutant lacking the central pair,
      displayed beating in the presence of 10 mM MgSO(4) and 0.2 mM ATP at about 22 Hz,
      while none beat with the same concentration of ATP and < or = 5 mM or > or = 25
      mM MgSO(4). The beat frequency and waveform of beating pf18 axonemes were similar
      to those of wild type axonemes beating under the same conditions. Similarly, 10
      50% of the axonemes beat in the presence of 0.5 M sucrose, 2.0 M glycerol, or 1.7
      M[10% (v/v)] ethanol. The appearance of motility did not correlate with the
      change in axonemal ATPase; however, these substances at those concentrations
      commonly increased the amplitude of nanometer-scale oscillation (hyper
      oscillation) in pf18 axonemes, as well as the extent of ATP-induced sliding
      disintegration of protease-treated axonemes. Axonemes of double mutants lacking
      both the central pair and various subspecies of inner-arm dynein also beat at
      increased MgSO(4) concentrations, but axonemes lacking outer-arm dynein in
      addition to the central pair did not beat. These and other observations suggest
      that small molecules perturb the regulation of microtubule sliding through some
      change in water activity or osmotic stress. Axonemes must have an intrinsic
      ability to beat without the central pair/radial spokes under a variety of non
      physiological solution conditions, as long as the outer dynein arms are present.
      Apparently, the major function of the central pair/radial spoke structures is to
      restore this activity under physiological conditions.

PMID- 10913965
TI  - Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from
      a patient with leukocyte adhesion deficiency-1: normal displacement in close
      quarters via chimneying.
AB  - The beta2 integrins are known to be important in the motile function of
      leukocytes in general and in the adhesive response to inflammatory stimuli in
      particular. In the current study, under direct microscopic observation with
      concomitant time-lapse video recording, we examined the locomotion of human blood
      PMN from a patient with Leukocyte Adhesion Deficiency-1 (LAD), a disorder in
      which beta2 integrins on the cell surface are markedly deficient in number or
      function. In thin slide preparations such that the leukocytes were somewhat
      compressed between slide and cover slip, PMNLAD exhibited normal random
      locomotion and chemotaxis, apparently by using the opposing surfaces to generate
      the force for locomotion (chimneying). In thicker preparations, an adherence
      deficit was evident, but chemotaxis still occurred, even by PMNLAD anticoagulated
      in EDTA. Consistent with the paucity of beta2 integrins on the surface of the
      PMNLAD was their failure to aggregate in the presence of antibodies to beta2
      integrins, even when they had been brought together by chemotaxis. We relate
      these findings to the reported independence from integrins of PMN in the lung
      vasculature in LAD, as well as in certain experimental conditions.

PMID- 10913967
TI  - Changes in the motility, morphology, and F-actin architecture of human dendritic
      cells in an in vitro model of dendritic cell development.
AB  - An in vitro model has been developed for analyzing the two developmental phases
      of human dendritic cell (DC) migration. Employing the age of the culture and the
      addition of GM-CSF, IL-4, and serum to regulate cellular phenotype, and glass
      coated with acid-precipitated human plasma proteins to facilitate persistent DC
      translocation, the model produces three sequential in vitro phenotypes with the
      following suggested in vivo counterparts: (1) DCs recently isolated from blood,
      which are highly polar and motile, and reflect the behavior of "undifferentiated"
      DCs that must extravasate from the blood stream and migrate into peripheral
      tissue; (2) large, nonmotile, stellate DCs, which reflect the highly
      "differentiated" signature phenotype of DCs in peripheral tissue, whose function
      is to capture foreign antigens; and (3) the large, motile "dedifferentiated" DCs,
      which reflect the behavior of "veiled cells" that have captured an antigen,
      retracted dendritic processes, migrated out of peripheral tissue, and are in the
      process of transporting a captured antigen to a proximal draining lymph node for
      presentation to T cells. Computer-assisted motion analysis of the three
      sequential phenotypes and fluorescent staining of F-actin reveal three unique
      behavioral states and unique cellular architecture consistent with inferred in
      vivo function. This in vitro model should serve as a starting point for
      elucidating the cues and molecular mechanisms involved in the regulation of DC
      differentiation and motility.

PMID- 10913968
TI  - Inhibition of myosin/moesin phosphatase by expression of the phosphoinhibitor
      protein CPI-17 alters microfilament organization and retards cell spreading.
AB  - Cell migration and cytokinesis require reorganization of the cytoskeleton,
      involving phosphorylation and dephosphorylation of proteins such as myosin II and
      moesin. Myosin and moesin bind directly to a regulatory subunit of myosin/moesin
      phosphatase (MMP) that contains a protein type-1 phosphatase (PP1) catalytic
      subunit. Here we examined the role of MMP in cytoskeletal dynamics using a
      phosphorylation-dependent inhibitor protein specific for MMP, called CPI-17.
      Fibroblasts do not express CPI-17, making them a null background to study effects
      of expression. Wild type CPI-17 in rat embryo fibroblasts caused (1) abnormal
      accumulation of cortical F-actin fibers, distinct from the stress fibers induced
      by expression of active RhoA; (2) progressive contraction of cell area, leaving
      behind filamentous extensions that stained for F-actin and moesin, but not
      myosin; and (3) significantly retarded spreading of fibroblasts on fibronectin
      with elevated myosin II light chain phosphorylation. A phosphorylation site
      mutant CPI-17(T38A) and inhibitor-2 (Inh2), another PP1-specific inhibitor
      protein, served as controls and did not elicit these same responses when
      expressed at the same level as CPI-17. Inhibition of myosin light chain kinase by
      ML-9 prevented the abnormal accumulation of cortical microfilaments by CPI-17,
      but did not reverse shrinkage in area, whereas kinase inhibitors HA1077 and H7
      prevented CPI-17-induced changes in microfilament distribution and cell
      contraction. These results highlight the physiological importance of
      myosin/moesin phosphatase regulation to dynamic remodeling of the cytoskeleton.

PMID- 10913969
TI  - Bone marrow transplantation for myelodysplasia.
AB  - Allogeneic bone marrow transplantation (BMT) is the only treatment modality that
      has consistently been demonstrated to cure patients with the myelodysplastic
      syndrome (MDS). Since the early 1980s, numerous publications have reported the
      results with BMT for over 700 patients with MDS and the lead patients are now
      disease-free for more than 16 years. Overall, these studies show that
      approximately 40% of patients are likely to be cured with allogeneic BMT. The
      best results have been reported for patients with refractory anemia who receive
      marrow from fully matched related donors, with 75% long-term disease-free
      survival rates. Factors that are associated with an increased risk of relapse
      and, thereby, shorter disease-free survival, include increased blast percentage
      and poor risk karyotype. Factors that are associated with an increased risk of
      non-relapse mortality and, in some studies, shorter disease-free survival,
      include longer disease duration, advanced patient age, therapy-related MDS, male
      patients, and use of mismatched or unrelated donors. However, favorable results
      have been seen in small studies of patients 55-66 years of age and in patients
      with refractory anemia undergoing matched unrelated donor BMT. Allogeneic BMT is
      appropriate therapy for patients with high or intermediate risk disease (risk
      category based on the International Prognostic Scoring System). The use of
      allogeneic BMT for patients with low risk disease is not well defined, but may be
      appropriate for particularly young individuals or those with a life-threatening
      single cytopenia.

PMID- 10913970
TI  - Nutrition and phylogeny of predacious yeasts.
AB  - Yeast predation was studied with respect to the range of its distribution among
      ascomycetous yeasts, the range of yeast species that can be affected, and
      nutritional aspects of the phenomenon. The yeasts identified as predators belong
      to the Saccharomycopsis clade as defined on the basis of rDNA sequence
      relatedness. The 11 recognized species in the clade, plus three undescribed but
      related Candida species, were shown to be incapable of utilizing sulfate as sole
      source of sulfur, and all but two (Saccharomycopsis capsularis and
      Saccharomycopsis vini) were observed to penetrate and kill other yeasts under
      some conditions. Other unrelated sulfate transport-deficient yeasts (strains in
      the genera Pichia and Candida and the two known species of Starmera) are not
      predacious. The predacious species vary considerably as to the optimal
      environmental conditions that favour predation. Some are inhibited by the
      presence of rich nitrogenous nutrients, organic sulfur compounds, or higher
      concentrations of ammonium nitrogen, whereas other species may be stimulated
      under the same conditions. An attempt was made to correlate prey susceptibility
      to the excretion of substances that stimulate the growth of predators, but no
      correlation was detected between the two phenomena. The range of susceptible prey
      covers both ascomycetes and basidiomycetes, and includes Schizosaccharomyces
      pombe, which was previously thought to be immune. The achlorophyllous alga
      Prototheca zopfii is not killed by predacious yeasts, but the initial steps of
      penetration have been observed in some cases. Predacious species attack other
      predacious species, and in some cases, young cultures may penetrate older
      cultures of the same strain.

PMID- 10913971
TI  - Fatty-acid biosynthesis in a branched-chain alpha-keto acid dehydrogenase mutant
      of Streptomyces avermitilis.
AB  - Fatty-acid biosynthesis by a branched-chain alpha-keto acid dehydrogenase (bkd)
      mutant of Streptomyces avermitilis was analyzed. This mutant is unable to produce
      the appropriate precursors of branched-chain fatty acid (BCFA) biosynthesis, but
      unlike the comparable Bacillus subtilis mutant, was shown not to have an obligate
      growth requirement for these precursors. The bkd mutant produced only straight
      chain fatty acids (SCFAs) with membrane fluidity provided entirely by unsaturated
      fatty acids (UFAs), the levels of which increased dramatically compared to the
      wild-type strain. The levels of UFAs increased in both the wild-type and bkd
      mutant strains as the growth temperature was lowered from 37 degrees C to 24
      degrees C, suggesting that a regulatory mechanism exists to alter the proportion
      of UFAs in response either to a loss of BCFA biosynthesis, or a decreased growth
      temperature. No evidence of a regulatory mechanism for BCFAs was observed, as the
      types of these fatty acids, which contribute significantly to membrane fluidity,
      did not alter when the wild-type S. avermitilis was grown at different
      temperatures. The principal UFA produced by S. avermitilis was shown to be delta
      9-hexadecenoate, the same fatty acid produced by Escherichia coli. This
      observation, and the inability of S. avermitilis to convert exogenous labeled
      palmitate to the corresponding UFA, was shown to be consistent with an anaerobic
      pathway for UFA biosynthesis. Incorporation studies with the S. avermitilis bkd
      mutant demonstrated that the fatty acid synthase has a remarkably broad substrate
      specificity and is able to process a wide range of exogenous branched chain
      carboxylic acids into unusual BCFAs.

PMID- 10913972
TI  - Mushroom (Agaricus bisporus) compost quality factors for predicting potential
      yield of fruiting bodies.
AB  - A quality model has been developed from parameters determining the interactions
      of physical, chemical, and biological factors during the preparation of mushroom
      compost for growing Agaricus bisporus. Our results show that a partial least
      square model based on the combination of pH, dry matter, ammonia, carbon,
      hydrogen, ash, Cu, Fe, and Na could explain nearly 90% of the variation in
      mushroom yield obtained from four compost comparative trials. The yields in the
      data base for generating the model ranged from 138 to 305 kg per ton of compost.
      The validity of the yield model has been confirmed in a trial carried out in
      collaboration with experienced commercial growers. This has significant
      implications for compost producers, as production efficiencies can be maintained
      by targeting the important parameters.

PMID- 10913973
TI  - Inactivation of phytotoxin produced by the rice sheath blight pathogen
      Rhizoctonia solani.
AB  - The rice sheath blight pathogen, Rhizoctonia solani, produces a toxin designated
      as RS-toxin, a carbohydrate compound containing mainly alpha-glucose and mannose.
      Different microflora were tested for RS-toxin inactivation. Isolates of
      Trichoderma viride inactivated this toxin when it was provided as the sole food
      source, and these isolates reduced the severity of toxin-induced symptoms and
      electrolyte leakage from rice cells. The best-performing isolate, TvMNT7,
      produced two extracellular proteins of 110 and 17 kDa. The high molecular mass
      protein was shown to have alpha-glucosidase activity. The purified 110 kDa
      protein was able to reduce RS-toxin activity.

PMID- 10913974
TI  - Enzymatic degradation of nitriles by a Candida guilliermondii UFMG-Y65.
AB  - Candida guilliermondii UFMG-Y65, isolated from a gold mine, was able to utilize
      different nitriles and the corresponding amides as sole source of nitrogen, at
      concentrations up to 2 M. Resting cells cultivated on YCB-acetonitrile medium
      showed nitrile hydrolyzing enzyme activities against acrylonitrile and
      benzonitrile. These enzymes were inducible and intracellular; the optimum pH was
      7.0-8.0, and the optimum temperature 25 degrees C-30 degrees C. Liquid
      chromatographic analysis indicated that C. guilliermondii UFMG-Y65 metabolized 12
      mM benzonitrile to 11 mM benzoic acid and 10 mM acrylonitrile to 7.9 mM acrylic
      acid. The results suggest that C. guilliermondii UFMG-Y65 may be useful for the
      bioproduction of amides and acids, and for the bioremediation of environments
      contaminated with nitriles.

PMID- 10913975
TI  - Optimizing the expression of a monoclonal antibody fragment under the
      transcriptional control of the Escherichia coli lac promoter.
AB  - The expression of a monoclonal antibody Fab fragment in Escherichia coli strain
      RB791/pComb3, induced with either lactose or isopropyl-beta-D-thiogalactoside
      (IPTG), was compared to determine if lactose might provide an inexpensive
      alternative to induction with IPTG. Induction of Fab expression imposed a
      metabolic load on the recombinant cells, resulting in lower final cell yields
      compared to the non-induced controls. An IPTG concentration of 0.05 mM was
      sufficient to achieve maximal expression of soluble Fab protein when inducing in
      the early-, mid-, or late-log phases of batch cultures grown using either glucose
      or glycerol as a carbon source. The largest overall yield of Fab fragments when
      using 0.05 mM IPTG was achieved by increasing the final yield of cells through
      glycerol feeding following induction in late-log phase. Lactose was as effective
      as IPTG for inducing Fab expression in E. coli RB791/pComb3. The greatest overall
      level of Fab expression was found when cells grown on glycerol were induced with
      2 g/L lactose in late-log phase. Since the cost of 0.05 mM of IPTG is
      significantly greater than the cost of 2 g/L lactose, lactose provides an
      inexpensive alternative to IPTG for inducing the expression of Fab fragments, and
      possibly other recombinant proteins, from the E. coli lac promoter.

PMID- 10913976
TI  - Isolation of Tn916-like conjugal elements from swine lot effluent.
AB  - Isolates of Enterococcus faecalis obtained from a swine farrowing house outflow
      were examined for genetic elements similar to Tn916. Of the enterococci isolated,
      71% were resistant to tetracycline. Among the tetracycline-resistant enterococci
      isolated from the outflow samples, approximately 34% were able to transfer the
      tetracycline resistance phenotype to Bacillus thuringiensis in cross-genus
      matings. The frequencies of transfer for 10 random isolates were comparable to
      those for transfer of Tn916 from E. faecalis to B. thuringiensis. In addition,
      these elements were shown to mobilize plasmid pC194 between Bacillus species, as
      did Tn916. Southern blot and polymerase chain reaction (PCR) analysis showed
      these elements share extensive structural homology with Tn916. The selected
      conjugal elements were capable of transfer to a Bacillus recipient in a soil
      environment. When the swine waste was introduced into the soil, the tetracycline
      resistant fecal enterococci levels rose from essentially undetectable levels to
      approximately 4 x 10(4) and remained at this level for 4 weeks. After six months,
      including one winter, levels had decreased to 5 x 10(3).

PMID- 10913977
TI  - Thatch biodegradation and antifungal activities of two lignocellulolytic
      Streptomyces strains in laboratory cultures and in golf green turfgrass.
AB  - The use of lignocellulolytic Streptomyces spp. as biological agents, to enhance
      thatch degradation in turf and to slow its rate of accumulation while controlling
      fungal growth in the thatch layer, was studied. In flask scale studies, two
      lignocellulolytic Streptomyces violaceusniger (= hygroscopicus) strains (YCED9
      and WYE53) decomposed thatch (> 30% dry weight) over a 12-week incubation period.
      Biodegradation was accompanied by production of extracellular cellulases,
      xylanases, and peroxidases. The accumulation of the polymeric, water-soluble
      lignin degradation intermediate acid, precipitable polymeric lignin (APPL), was
      also observed. Residual thatch from 12-week-old cultures had an increased lignin
      to-carbohydrate ratio, an indication that although lignin was metabolized,
      carbohydrates were preferential carbon sources for these actinomycetes. A spore
      containing soluble dry powder formulation was used as an inoculum in an in situ
      field experiment. This formulation was maintained in storage at 4 degrees C for
      over two years without viability loss. Results from the golf green experiment
      showed that although treated thatch layers in established greens were not
      appreciably reduced over the course of one summer, the Streptomyces were active
      and maintained their populations within the thatch, while fungal growth was
      suppressed as compared to controls. The results show that treatment of turfgrass
      with these Streptomyces may be useful for the long-term control of fungal
      populations within the thatch. Longer field studies are required to assess the
      long-term potential for also controlling thatch build-up and fungal pathogens.

PMID- 10913978
TI  - Characterization of subterranean bacteria in the Hungarian Upper Permian
      Siltstone (Aleurolite) Formation.
AB  - The main purpose of this work was to study the microbiology of the Hungarian
      Upper Permian Siltstone (Aleurolite) Formation, to assess the safety of future
      underground repositories for nuclear waste. Sixty-seven air, groundwater,
      technical water, rock, and surface samples were collected aseptically from
      different depths. The number of aerobic and anaerobic isolates was 277. The
      mesophilic minimum and maximum CFU counts of the air samples were 1.07-5.84 x
      10(2).mL-1 (aerobic) and 0.22-1.04 x 10(2).mL-1 (anaerobic), respectively; those
      of the water samples were 0.39-1.25 x 10(5).mL-1 (aerobic) and 0.36-3.9 x
      10(3).mL-1 (anaerobic); those of the technical water samples were 0.27-5.03 x
      10(6).mL-1 (aerobic) and 4 x 10(5)-->10(6).mL-1 (anaerobic); and those of the
      aleurolite samples were 2.32 x 10(2)-2.47 x 10(5).g-1 (aerobic) and 0.45-9.5 x
      10(2).g-1 (anaerobic). In the groundwater, the thermophilic aerobic bacteria
      count was 0-2.4 x 10(2).mL-1 and the thermophilic anaerobic bacteria count was
      0.43-4.6 x 10(4).mL-1. The gases produced by the 16 gas-forming isolates were CO2
      (aerobic isolates), and CO2 and H2 (anaerobic isolates). About 20% of the aerobic
      isolates produced siderophores. The proportions of organic acid producers were
      lowest in aerobic and anaerobic isolates from the aleurolite, 13% and 14%,
      respectively. The highest proportions of acid producers in the aerobic and
      anaerobic isolates from the air samples were 63% and 54%. Altogether 160 of the
      aerobic isolates and 52 of the anaerobic isolates were spore formers. The
      radiosensitivity of the aerobic isolates was also determined; the D10 values of
      the sporeformers ranged between 0.8-2.44 kGy. Our results indicate that the
      sulfate-reducing bacteria and the production of complexing agents (siderophores)
      may contribute to the mobilization of radionuclides from underground
      repositories. As well, microbial gas production can influence the environmental
      conditions. The variability in bacterial radiotolerance indicates the
      biodiversity at this potential disposal site. These facts must be considered
      during the planning of a nuclear waste repository.

PMID- 10913979
TI  - Occurrence of pathogenic microorganisms in the Saint Lawrence River (Canada) and
      comparison of health risks for populations using it as their source of drinking
      water.
AB  - A 300-km portion of the Saint Lawrence hydrological basin in the province of
      Quebec (Canada) and 45 water treatment plants were studied. River water used by
      drinking water treatment plants was analyzed (6-L sample volumes) to determine
      the level of occurrence of bacterial indicators (total coliforms, fecal
      coliforms, and Clostridium perfringens) and pathogens (Giardia lamblia,
      Cryptosporidium, human enteric viruses). Pathogens and bacterial indicators were
      found at all sites at a wide range of values. Logistic regression analysis
      revealed significant correlations between the bacterial indicators and the
      pathogens. Physicochemical and treatment practices data were collected from most
      water treatment plants and used to estimate the level of removal of pathogens
      achieved under cold (0 degree C-4 degrees C) and warm (20 degrees C-25 degrees C)
      water temperature conditions. The calculated removal values were then used to
      estimate the annual risk of Giardia infection using mathematical models and to
      compare the sites. The estimated range of probability of infection ranged from
      0.75 to less than 0.0001 for the populations exposed. Given the numerous
      assumptions made, the model probably overestimated the annual risk, but it
      provided comparative data of the efficacy of the water treatment plants and
      thereby contributes to the protection of public health.

PMID- 10913980
TI  - Eight UCA codons differentially affect the expression of the lacZ gene in the
      divE42 mutant of Escherichia coli.
AB  - In the divE mutant, which has a temperature-sensitive mutation in the tRNA1(Ser)
      gene, the synthesis of beta-galactosidase is dramatically decreased at the non
      permissive temperature. In Escherichia coli, the UCA codon is only recognized by
      tRNA1(Ser). Several genes containing UCA codons are normally expressed at 42
      degrees C in the divE mutant. Therefore, it is unlikely that the defect is due to
      the general translational deficiency of the mutant tRNA1(Ser). In this study, we
      constructed mutant lacZ genes, in which one or several UCA codons at eight
      positions were replaced with other serine codons such as UCU or UCC, and we
      examined the expression of these mutant genes in the divE mutant. We found that a
      single UCA codon at position 6 or 462 was sufficient to cause the same level of
      reduced beta-galactosidase synthesis as that of the wild-type lacZ gene, and that
      the defect in beta-galactosidase synthesis was accompanied by a low level of lacZ
      mRNA. It was also found that introduction of an rne-1 pnp-7 double mutation
      restored the expression of mutant lacZ genes with only UCA codons at position 6
      or 462. A polarity suppressor mutation in the rho gene had no effect on the
      defect in lacZ gene expression in the divE mutant. We propose a model to explain
      these results.

PMID- 10913981
TI  - Mutational analysis of the C-terminal anchoring domains of Streptococcus mutans
      P1 antigen: role of the LPXTGX motif in P1 association with the cell wall.
AB  - The salivary agglutinin-interacting adhesin P1 of Streptococcus mutans is
      anchored to the cell wall via the carboxy (C) terminus, which contains a wall
      associated domain, a conserved LPXTGX motif, a hydrophobic domain, and a charged
      tail. To further investigate the role of the C-terminal anchoring regions in cell
      wall sorting and anchoring, mutational analysis was performed on P1 in this
      study. Three truncated P1 mutants and seven site-directed mutants were generated
      by a polymerase chain reaction-based technique. The mutated P1 genes were
      returned to the P1-negative S. mutans SM3352 for expression and localization
      studies by ELISA and Western immunoblotting. The results showed that P1 mutants
      with deletion of the hydrophobic domain and charged tail, or deletion of the
      charged tail alone resulted in the secretion of P1 to the culture medium. Results
      from cellular fractionation experiments with the truncated mutants showed that P1
      was not trapped in the membrane or cytoplasm. The site-directed mutants showed
      normal distribution of P1 to the cell surface as compared to the wild-type.
      However, when cell walls prepared from the site-directed mutants were boiled with
      SDS, P1 could be removed readily from the mutants with Thr residue in the LPNTGV
      motif, altered to either Ser (T1531S) or Phe (T1531F); the mutant with Thr and
      Gly residues altered to two Phe residues (TG1531-1532FF), and the LPNTGV-deleted
      mutant (LPNTGV-). In contrast, the wild-type P1 and the other three site-directed
      P1 mutants (P1529V, N1530I, and G1532F) could not be removed by boiling SDS. When
      the cell wall P1s from the wild-type, mutants P1529V, N1530I, and G1532F were
      reacted with an antibody directed against the hydrophobic domain and charged
      tail, no reaction was detected. However, P1s from mutants T1531S, T1531F, TG1531
      1532FF, and LPNTGV- were recognized by the antibody, indicating that the
      inability of these mutated P1s to firmly link to the cell wall was the result of
      failure in proteolytic cleavage of the hydrophobic domain and charged tail. In
      summary, the results suggest that the charged tail plays a decisive role in
      sorting P1 to the cell surface, while the LPXTGX motif determines the nature of
      P1-cell wall association. The Thr residue of the LPXTGX motif is required for
      enzymatic processing to link P1 to the cell wall, presumably via a covalent bond.

PMID- 10913982
TI  - Acellular pertussis vaccines.

PMID- 10913983
TI  - Novel pharmacological approaches to the treatment of schizophrenia.
AB  - Schizophrenia is a devastating mental disease that affects the human population
      worldwide with an incidence of about 1%. Over the last decades basic and clinical
      research has considerably increased our understanding of the pathophysiology of
      schizophrenia, as well as the mechanism of action of antipsychotic compounds
      (neuroleptics), and new atypical neuroleptics with equipotent or improved
      antipsychotic effects and fewer motoric side effects have been developed.
      However, the pharmacological intervention does not effectively treat all the
      symptoms of the disease, and there is still a need for new, more effective
      antipsychotic compounds. Studies of brain function have demonstrated a reduced
      activation of prefrontal cortical areas during cognitive tasks in schizophrenics.
      It is hypothesized, that this hypofrontality is associated with a reduced
      dopaminergic tonus in the prefrontal cortex, which subsequently causes the
      negative symptoms of schizophrenia, such as apathy and social withdraw. It has
      also been suggested, that increased dopaminergic activity in striatal areas is
      related to the wellknown positive schizophrenic symptoms, such as delusions and
      hallucinations. The present thesis addresses the regional effects of prototypical
      and atypical neuroleptics on nerve cell activity and dopaminergic tonus in three
      rat brain areas with special relevance for the pharmacological effects of
      neuroleptics. Finally, new pharmacological approaches to the medical treatment of
      schizophrenia are suggested based on our experimental results. Initially, the
      effects of the prototypical neuroleptic haloperidol and the atypical neuroleptic
      clozapine on nerve cell activity in the rat forebrain were investigated by
      measuring the regional expression of the Fos protein. The Fos protein is regarded
      as a marker of cellular activity and was measured by use of immunohistochemical
      techniques i) in the medial prefrontal cortex (PFC), probably involved in the
      negative symptoms of schizophrenia, ii) in the nucleus accumbens (NAc), probably
      involved in the positive symptoms of schizophrenia and iii) in the dorsolateral
      striatum (DLSt), most likely involved in the motoric side effects of
      neuroleptics. Clozapine increases Fos protein immunoreactivity in the PFC with no
      or minimal effects in the DLSt. In contrast, haloperidol increases Fos protein
      immunoreactivity in the DLSt with minor effect in the PFC. Other atypical
      neuroleptics (risperidone, sertindole and NNC 22-0031) induced a Fos protein
      expression pattern different from haloperidol: The atypical compounds exhibit a
      larger ratio between Fos protein expression in PFC and DLSt than measured for
      haloperidol. These results are in accordance with the reported beneficial effects
      of clozapine, risperidone and sertindole on negative symptoms of schizophrenia
      and their lower degree of motoric side effects compared to haloperidol. All
      neuroleptics induced Fos protein immunoreactivity in the NAc, in accordance with
      their ability to reduce positive psychotic symptoms in schizophrenics. The
      microdialysis technique was used to investigate the regional dopaminergic effects
      of the above mentioned antipsychotic compounds by measuring interstitial levels
      of the dopamine metabolite dihydroxyphenylacetic acid ([DOPAC]i) in PFC, NAc and
      DLSt. All antipsychotics tested increased [DOPAC]i in the NAc, whereas the
      atypical antipsychotics clozapine, risperidone, sertindole and NNC 22-0031--in
      contrast to haloperidol--preferentially increased [DOPAC]i in PFC compared to
      DLSt. Also these results are in concordance with the clinical effects of
      clozapine, risperidone, sertindole and haloperidol and support the hypothesis
      that reduced dopaminergic tone in the prefrontal cortex relates to the negative
      symptoms of schizophrenia. All clinically efficacious neuroleptics block central
      dopamine D2 receptors, which include the dopamine D2, D3 and D4 receptor
      subtypes. The present thesis characterizes a dopamine D3 receptor agonist, cis-OH
      PBZI.

PMID- 10913985
TI  - Pulmonary function after exercise with special emphasis on diffusion capacity.
AB  - The present work focuses on pulmonary gas exchange during repeated rowing to
      exhaustion and the recovery of pulmonary diffusion capacity for carbon monoxide
      (DL) after exercise in healthy young subjects. The components of DL are examined
      at rest using the single breath method at two different alveolar O2 tensions.
      Electrical impedance and 99mTechnetium labelled erythrocytes were used to
      evaluate the recovery of blood distribution. Special attention has been given to
      the role of the inspiratory muscles as a limiting factor for VO2max and
      performance. The documentation in this study of a reduced DL several hours after
      exercise conflicts with the prerequisites of optimal conditions for high
      metabolic rates in elite athletes. Even low intensity exercise induces a
      reduction in DL, and together with the fact that a diuretic does not attenuate
      this decrease, emphasises that the reduction in DM is not due to an interstitial
      pulmonary edema. The major part of the reduction is due to a decreased CBV
      reflected in a reduction of VC and a minor part is caused by an injury to the
      membrane component carried over from exercise. The ability in athletes to repeat
      exhaustive exercise within 2 h indicates that the slow recovery of DL is not
      combined with either impaired pulmonary gas exchange or performance. Thus, an
      acute diffusion limitation and a low pH cause the desaturation in some athletes
      during exhaustive exercise. Despite the inspiratory muscles having a slower
      response to endurance training compared with the cardiovascular system, selective
      training of the inspiratory muscles does not improve either VO2max or
      performance. This indicates that maximal inspiratory pressure is not a limiting
      factor for maximal exercise and that the stimuli to increase VA depends on an
      increased metabolic rate; stressing the role of the peripheral chemoreceptors.
      Together with the post-exercise decrease in ANP, the reduction in DL may be
      involved in the mechanism increasing the total blood volume in endurance trained
      athletes.

PMID- 10913984
TI  - Inflammatory pain in experimental burns in man.
AB  - Human experimental pain models are important tools in pain research. The primary
      aims of pain research in normal man is 1) to provide insight in pain mechanisms,
      2) to provide a rational basis for clinical trials of pain relieving
      interventions, and 3) to confirm the anti-nociceptive effects demonstrated in
      animal models. Most often clinical pain is due to tissue damage leading to acute
      inflammation and hyperalgesia, but only few human pain models have examined pain
      responses in injured tissues. Therefore, models with controlled and reversible
      tissue trauma are needed. The human burn model is an example of such a model, and
      several groups have performed studies of analgesics and pain mechanisms based on
      the model. The thesis aims to provide a critical review of the human burn model
      as a tool in pain research, and to give suggestions for development of the model
      and future research. The pain and inflammatory responses to superficial thermal
      burns in skin have been studied in healthy volunteers. Burns have the potential
      for releasing most of the inflammatory and chemical mediators that produce
      sensitisation and excitation of nociceptors, and the intense nociceptive input
      during injury produces sensitisation of central neurones in the nociceptive
      pathway. Pain and hyperalgesia have been evaluated in the model by thermal,
      various mechanical, and electrical stimuli. The different methods of pain
      assessments are discussed to clarify the underlying neural mechanisms, the
      questions that can be addressed by the measurements, and the discrepancies in
      results between studies. Inflammation has been evaluated in the model by skin
      erythema intensity, area of flare, and blister formation. The major determinant
      of skin erythema intensity is the amount of blood in the most superficial part of
      the dermis, and burn-induced erythema may be primarily due to congestion of
      capillary loops and postcapillary venules. The area of flare may be used to
      evaluate the efferent function of heat-sensitive A delta- and C-fibre
      nociceptors, whereas blisters may be used to assess edema formation and the
      degree of injury. Hyperalgesia is induced immediately by the burns and lasts
      about 24 h dependent on the intensity of the heat stimulus. The burns heal
      without sequela. A study of the reproducibility of pain assessments in the burn
      model has shown that measures based on repeated measurements were significantly
      more reproducible than measures based on single time points. Further, within-day
      reproducibility was better than between-day reproducibility. Within-day
      variations of heat pain responses to 45 degrees C and 47 degrees C were smaller
      than that of pain responses to 43 degrees C, suggesting that assessments using
      clearly painful stimuli may be more reproducible. A methodological study also
      demonstrated that habituation to experimental pain developed as the study
      proceeded. Habituation is common in experimental pain models, and dividing
      analgesics and placebo evenly between the study days is one way of eliminating
      the effects of habituation. The use of simultaneous right-left comparisons
      represents the ideal design when possible. The burn model has been a valuable
      tool in the study of pain mechanisms. Hyperalgesia to heat in the burned area
      (primary hyperalgesia) is mediated by sensitisation of C-fibre mechano-heat
      sensitive (CMH) nociceptors and A delta-fibre mechano-heat-sensitive (AMH)
      nociceptors of type I in hairy skin. A contribution from sensitised CNS neurones
      is likely, and the sensitisation of nociceptors is confined to the injured area.
      The presence of hyperalgesia to heat in normal skin surrounding a burn (secondary
      hyperalgesia) has been demonstrated in several studies, but the pain threshold
      may be unaltered. The mechanisms for primary hyperalgesia to mechanical stimuli
      may be both peripheral and central, but the importance of peripheral mechanisms
      is unclear and central mechanisms may account for mechanical hyperalgesia in both
      the primary and th

PMID- 10913986
TI  - Transnasal gastroscopy.
AB  - INTRODUCTION: The use of transnasal gastroscopy (TNG) has not previously been
      described in a Danish hospital. The method seems to be better tolerated compared
      with conventional oral gastroscopy. METHODOLOGY: Patients scheduled for
      diagnostic gastroscopy were included, and examined with a thin endoscope
      transnasally (Olympus XGIF-N200 prototype, diameter 6 mm). RESULTS: Sixty
      patients were included, and transnasal gastroscopy was possible in 56 patients
      (93%). Two patients were examined transorally, as there were no passage through
      the nose. One patient had fluid retention in the stomach, and in another patient
      the endoscope looped continuously in the esophagus, preventing introduction into
      the stomach. The quality in 48 examinations (80%) was satisfactory. Unsedated
      examination was possible with 38 patients (68%), and 55% of patients did not have
      gag-reflexes or nausea. The unpleasantness of TNG was rated on a scale from 1 to
      4, and the median score was 2 (slightly unpleasant). TNG would be the method of
      choice in 88% of patients, if they should undergo another gastroscopy in the
      future. Fifteen patients had uncomplicated epistaxis as the only complication.
      Pulse rate and oxygen saturation values were stable during the TNG examinations.
      CONCLUSION: TNG with a thin endoscope seems to be well tolerated by the patients,
      this is supported by the subjective experience of the patients, and also by the
      stable values of oxygen saturation and heart rate during the examinations.

PMID- 10913987
TI  - Planned second look endoscopy in patients with bleeding duodenal or gastric
      ulcers.
AB  - INTRODUCTION: Preliminary studies have suggested a beneficial effect of second
      look endoscopy in patients with bleeding peptic ulcers. METHODOLOGY: We have
      performed a retrospective survey of seventy patients with bleeding peptic ulcers
      admitted to our unit in the period 1 September 1996-31 March 1998. Planned second
      look endoscopy and repeated sclerotherapy were standard care. The effects were
      evaluated by comparing the expected number of rebleeders with actual rebleeders.
      At the same time we assessed predicting factors for rebleeding. RESULTS: Fifteen
      of the admitted seventy patients were found to rebleed after initial
      sclerotherapy. The overall success rate of endoscopic therapy was 63/70 patients
      (90%). Six patients (9%) had to undergo surgery to obtain haemostasis, and one
      patient died suddenly after the second endoscopic sclerotherapy. Perforation was
      seen in two patients (3%) and the total mortality (30 days) was 4% (three
      patients). The most important factor predicting rebleeding was the occurrence of
      active bleeding at the initial endoscopy. CONCLUSION: From the literature we
      could expect that twenty to twenty-five patients would rebleed, comparing this
      with the findings of the present study suggests a beneficial effect on rebleeding
      rate of patients treated with planned second look endoscopy. Future controlled
      trails should verify this hypothesis.

PMID- 10913988
TI  - Infantile hypertrophic pyloric stenosis. Decreasing incidence.
AB  - INTRODUCTION: The study aimed to prove or disprove a clinical suspicion of a
      decreasing frequency of pyloric stenosis. METHOD: Retrospective review of
      hospital records of all children operated for pyloric stenosis in the hospitals
      of the County of Viborg from 1 January 1973 to 31 December 1997. This regional
      review was supplemented by a nationwide study, in which the National Registry of
      Patients was searched for the diagnosis number and the operation code of pyloric
      stenosis during the period 1 January 1977 to 31 December 1997. RESULTS: One
      hundred and forty-seven children were operated for infantile hypertrophic pyloric
      stenosis in Viborg County during the period in question. When calculated in five
      year periods, the respective numbers per 1000 liveborn children were: 1.6, 2.4,
      2.0, 2.8, and 0.9. Only one child was operated per year during 1996 and 1997,
      compared with an average of seven children annually during the preceding 20
      years. The same tendency was found in the nationwide study. Until 1993 an average
      of 160 children were operated per year, i.e. 2.2 to 3.2 per 1000 liveborn
      children. From 1993-1997 inclusive the number decreased to 1.4. In 1996 and 1997,
      respectively, 75 and 76 children were operated, i.e. 1.1 per 1000 liveborn
      children. CONCLUSION: There has been a significant decrease in the incidence of
      children with infantile hypertrophic pyloric stenosis, both in the County of
      Viborg and in the whole of Denmark. The decrease, which started in 1993, has for
      unknown reasons continued to accelerate ever since. The decrease coincides with
      changing recommendations concerning the positioning of infants during sleep, but
      a causal connection is uncertain.

PMID- 10913989
TI  - Endoscopic placement of self-expanding metal stents for treatment of colorectal
      obstruction with long-term follow-up.
AB  - INTRODUCTION: Relief of colorectal obstruction by means of self-expandable metal
      mesh stents (SEMS) has been suggested for palliation and acute decompression
      followed by optimization of the patients' general condition prior to definitive
      surgery. METHODOLOGY: Twelve patients with high operative risk and/or metastatic
      disease were selected for stenting with a dedicated colorectal partly covered
      SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). RESULTS: Stent
      deployment was successful in nine, two of whom had total obstruction. In one a
      guidewire perforation was treated conservatively. In two patients (one benign
      stricture, and one rectal cancer) the stents migrated within three weeks. One re
      obstructed. In the remaining six patients colonic decompression was achieved, and
      the stents have been patent until death after median 116 days (33-292 days).
      CONCLUSION: These results are promising, but data from several centres should be
      compiled prospectively in a standardized fashion in order to allow for assessment
      of the method's safety and success rates before randomised trials can be
      initiated.

PMID- 10913990
TI  - Extinction can be enhanced by a concurrent excitor.
AB  - Five experiments used rat subjects to investigate the impact on extinction of the
      presence of other conditioned stimuli. In Experiments 1 (Pavlovian magazine
      approach) and 2 (instrumental discriminative training), an excitatory stimulus
      (X) was extinguished alone, in conjunction with a previously reinforced other
      stimulus (A), in conjunction with previously nonreinforced other stimulus (B), or
      it was spared extinction. Responding during extinction was greatest to AX, and
      subsequent testing of X alone showed AX extinction to have produced the most
      decrement to X. Experiment 3 found similar results using a within-subject design.
      Experiment 5 continued separate reinforced presentations of A during extinction.
      This procedure not only promoted extinction of X but also converted it into a
      conditioned inhibitor. These experiments bear on the mechanisms of overshadowing
      and stimulus processing, as well as provide information on the determinants of
      extinction.

PMID- 10913991
TI  - Factors influencing the salience of temporal cues in the discrimination of
      synthetic Japanese monkey (Macaca fuscata) coo calls.
AB  - If temporal position of a frequency inflection is the most salient communication
      cue in Japanese macaque smooth early and smooth late high coos, then macaques
      should perceive coos differing only along the early-late dimension as belonging
      to different classes. The perceived similarity of synthetic coos and temporally
      reversed variants were evaluated, using multidimensional scaling of macaque
      discrimination latencies. Original calls and calls temporally reversed in the
      frequency domain could be discriminated if the peak was near a call endpoint but
      not if the frequency peak in the original call was near the coo midpoint.
      Perceived similarity of such calls was inversely related to the amount of
      frequency modulation. Temporal reversals of amplitude contours were also
      conducted. Although macaques are quite sensitive to amplitude increments,
      reversal of the relatively flat amplitude contours of these calls did not affect
      discrimination responses.

PMID- 10913992
TI  - Serial learning by rhesus monkeys: II. Learning four-item lists by trial and
      error.
AB  - Three rhesus macaque monkeys were trained to produce novel 4-item lists (A-->B-
      >C-->D) on which all items were displayed from the start of training. Subjects
      were previously trained to produce 4-item lists by adding one item at a time (A,
      A-->B, A-->B-->C, and A-->B-->C-->D; lists K. B. Swartz et al., 1991). Those
      lists could be mastered by responding to each new item last. To learn lists on
      which all items were displayed from the start of training, subjects had to recall
      the consequences of errors and correct responses to each item. Errors ended the
      trial; correct responses to A, B, or C allowed the trial to continue. A correct
      response to D produced food reward. Although the probability of executing a 4
      item list correctly by chance was .04, each subject mastered 4 novel 4-item lists
      by trial and error. The ability of monkeys to use a trial-and-error strategy to
      learn novel lists provides a basis for studying the development of serial
      expertise in animals.

PMID- 10913993
TI  - Two- versus three-alternative concurrent-chain schedules: a test of three models.
AB  - Two experiments with pigeons used concurrent-chain procedures with variable
      interval schedules as initial links and different delays to food as terminal
      links. Two schedules were present in all sessions, but a 3rd schedule was
      alternately present and absent in successive sessions. When the 3rd schedule
      delivered food with no terminal-link delay, the presence of this schedule led to
      an increase in preference for the schedule with the shorter terminal link of the
      2 unchanged schedules. When the terminal-link delay for the 3rd schedule was 30
      s, the presence of this schedule led to a decrease in preference for the schedule
      with the shorter terminal link of the 2 unchanged schedules. These results are
      inconsistent with the predictions of R. Grace's (1994) contextual-choice model,
      but they are consistent with 2 other mathematical models--delay-reduction theory
      and the hyperbolic value-added model.

PMID- 10913994
TI  - Presence/absence-sample matching by pigeons: divergent retention functions may
      result from the similarity of behavior during the absence sample and the
      retention interval.
AB  - Divergent choose-absence retention functions typically found in pigeons following
      presence/absence-sample matching have been attributed to the development of a
      single-code/default coding strategy. However, such effects may result from
      adventitious differential responding to the samples. In Experiment 1, retention
      functions were divergent only when differential sample responding could serve as
      the basis for comparison choice. In Experiment 2, when pecking did not occur
      during the retention interval, a choose-absence bias was found, but when pecking
      occurred during the retention interval, a choose-presence bias resulted. In
      Experiment 3, positive transfer was found when a stimulus associated with the
      absence of pecking replaced the absence sample but not when a stimulus associated
      with pecking replaced the presence sample. Thus, presence/absence-sample matching
      may not encourage the development of a single-code/default coding strategy in
      pigeons.

PMID- 10913995
TI  - Timing for the absence of a stimulus: the gap paradigm reversed.
AB  - Contrary to data showing sensitivity to nontemporal properties of timed signals,
      current theories of interval timing assume that animals can use the presence or
      absence of a signal as equally valid cues as long as duration is the most
      predictive feature. Consequently, the authors examined rats' behavior when timing
      the absence of a visual or auditory stimulus in trace conditioning and in a
      "reversed" gap procedure. Memory for timing was tested by presenting the stimulus
      as a reversed gap into its timed absence. Results suggest that in trace
      conditioning (Experiment 1), rats time for the absence of a stimulus by using its
      offset as a time marker. As in the standard gap procedure, the insertion of a
      reversed gap was expected to "stop" rats' internal clock. In contrast, a reversed
      gap of 1-, 5-, or 15-s duration "reset" the timing process in both trace
      conditioning (Experiment 2) and the reversed gap procedure (Experiment 3). A
      direct comparison of the standard and reversed gap procedures (Experiment 4)
      supported these findings. Results suggest that attentional mechanisms involving
      the salience or content of the gap might contribute to the response rule adopted
      in a gap procedure.

PMID- 10913996
TI  - Contextual control of long-term habituation in rats.
AB  - This study examined contextual control of long-term habituation and whether such
      effects are dependent on the habituating response system. Habituation of the
      acoustic startle response transferred from the home cage to the testing context,
      whereas habituation of lick suppression was context specific (Experiments 1 and
      2). Contextual control of habituation was demonstrated between 2 experimental
      contexts for lick suppression to a tone (Experiment 3) and bar-press suppression
      to a light (Experiment 4). Experiment 5 extinguished habituation of lick
      suppression and the orienting response to a tone with 27 exposures to the
      habituation context. Context specificity of both responses also was found.
      Previous failures to demonstrate contextual control of habituation may be due to
      the choice of response system and to less sensitive procedures to detect response
      recovery. The habituation mechanism for startle is independent from the process
      or processes that underlie habituation in other response systems, but the nature
      of these mechanisms is not yet known.

PMID- 10913997
TI  - Mechanisms of second-order conditioning with a backward conditioned stimulus.
AB  - Five conditioned suppression experiments with rats examined the conditions under
      which backward pairings endow a first-order conditioned stimulus (CS1) with the
      ability to serve as a secondary reinforcer. Experiments 2-5B found evidence for
      excitatory second-order conditioning (SOC) if, during first-order pairings, the
      US-CS1 interval was 0 s rather than 3 s. Levels of SOC were comparable after
      forward and backward pairings (Experiments 1-3), and were unaffected by
      extinction of CS1 after SOC (Experiment 3). These results suggest that forward
      and backward CS1s support SOC for the same reason, and they call into question
      the need to invoke any special mechanism such as memory integration.

PMID- 10913998
TI  - Interference from irrelevant features on visual discrimination by macaques
      (Macaca fuscata): a behavioral analogue of the human Stroop effect.
AB  - To study the operation of selective attention in a conflict situation with
      automatic processes, we trained 4 Japanese macaques (Macaca fuscata) extensively
      on a manual go/no-go task. The monkey had to discriminate either the color,
      shape, motion direction, or location of a visual stimulus. In each trial, the
      behavioral meaning of the relevant feature (go or no-go) could either be
      congruent or incongruent with irrelevant features of the same stimulus. Reaction
      times were slowed, and error rates increased when irrelevant stimulus features
      were incongruent with the required response. The effects were obtained when the
      monkey attended to the color, shape, or motion direction, but not when it
      attended to the location of the stimulus. The effects were cumulative so that the
      interference from 1 incongruent feature was smaller than that from 2 incongruent
      features. We propose that the present paradigm provides a behavioral analogue of
      the human Stroop effect.

PMID- 10913999
TI  - A novel contextual dimension for use with an operant chamber: from simple to
      hierarchical forms of learning.
AB  - A novel procedure is described in which the floor temperatures (warm and cool) in
      an operant chamber are used as contextual cues in 2 experiments with rats.
      Experiment 1 demonstrated that rats learn the relationship between these thermal
      contexts and auditory stimuli that have been paired with them. Experiment 2
      showed that thermal contexts can serve a conditional function that (a) reflects
      the operation of a mechanism that is common to conventional, visual contexts and
      (b) is bound to these contexts' ability to retrieve the nature of the
      relationship between the auditory stimuli and food.

PMID- 10914000
TI  - Detection of DNA cleavage in apoptotic cells.
AB  - At least two discrete deoxyribonuclease activities can be detected during
      apoptotic death, one that generates 30- to 500-kilobase pair (kbp) domain-sized
      fragments and another that mediates internucleosomal DNA degradation. The latter
      nuclease has been identified as the caspase-activated deoxyribonuclease
      (CAD)/CPAN, a unique enzyme that is normally inhibited by the regulatory subunit
      ICAD (inhibitor of CAD)/DFF45 (DNA fragmentation factor). In this chapter,
      techniques widely used to detect DNA cleavage in apoptotic cells, including
      pulsed-field gel electrophoresis, conventional agarose gel electrophoresis, and
      terminal transferase-mediated dUTP nick end-labeling (TUNEL), are briefly
      reviewed. In addition, the use of ICAD to inhibit apoptosis-associated nuclease
      activity is illustrated. When properly applied, these techniques are widely
      applicable to the characterization of apoptotic cells.

PMID- 10914001
TI  - Detection of apoptosis by annexin V labeling.

PMID- 10914002
TI  - Analysis of apoptotic cells by flow and laser scanning cytometry.
AB  - A large number of flow cytometric methods to identify apoptotic cells and analyze
      morphological, biochemical, and molecular changes that occur during apoptosis
      have been developed. These methods are also applicable to the laser scanning
      cytometer (LSC), a microscope-based cytofluorometer that combines advantages of
      flow and image cytometry and that, by offering a possibility of assessment of
      cell morphology, is of particular utility in analysis of apoptosis. Apoptosis
      related changes in cell morphology associated with cell shrinkage and
      condensation of cytoplasm and chromatin are detected by measurements of the
      intensity of light scatter of the laser beam in the forward and 90 degrees angle
      directions. Changes in plasma membrane composition and function are analyzed by
      its altered permeability to certain dyes and by the appearance of
      phosphatidylserine, which reacts with annexin V-fluorochrome conjugates on the
      external surface of the membrane. Decrease in mitochondrial transmembrane
      potential is measured with several fluorochromes of the rhodamine or carbocyanine
      family. DNA fragmentation is detected either by measurement of cellular DNA
      content after elution of the degraded DNA from the cell before or during the
      staining procedure or by in situ labeling DNA strand breaks. Apoptotic cells are
      then recognized either on the basis of their reduced DNA-associated fluorescence
      as the cells with fractional DNA content ("sub-G1 cells"), or as the cells with
      an extensive number of DNA breaks, respectively. Advantages and limitations of
      the preceding methods are discussed and their adaptation to LSC is presented.

PMID- 10914003
TI  - Quantitative measurement of apoptosis induced by cytotoxic T lymphocytes.
AB  - Cytotoxic T lymphocytes destroy virus-infected and malignant cells through the
      induction of apoptosis. This form of cell death is characterized by a number of
      cellular changes including cell shrinkage and membrane blebbing, chromatin
      condensation and DNA fragmentation, externalization of phosphatidylserine to the
      outer leaflet of the plasma membrane, and disruption of the inner mitochondrial
      transmembrane potential (delta psi m). Cell death induced by cytotoxic T
      lymphocytes is associated with similar morphological and biochemical features.
      Here we demonstrate how methods typically employed to detect apoptotic cells can
      be adapted to monitor cell death mediated by cytotoxic T lymphocytes. We have
      specifically selected techniques that allow quantitative evaluation of death
      including membrane changes, DNA fragmentation, and mitochondrial depolarization.

PMID- 10914004
TI  - Apoptotic nuclease assays.
AB  - One of the defining biochemical characteristics of apoptosis is the degradation
      of chromatin into regularly sized (oligonucleosomal and approximately 30- to 50
      kb) fragments. Because destruction of the genome represents a clear commitment to
      death, considerable interest has focused on this component of apoptosis and
      numerous assays have been developed to assess the relevant nucleases involved.
      These assays fall into two major categories: (1) those independent of chromatin
      structure and (2) those dependent on chromatin structure. The chromatin
      independent assays (plasmid degradation assay and radioactive gel assay) examine
      the ability to degrade naked DNA and are advantageous because of their simplicity
      and speed and ability to analyze single nucleases or mixtures of nucleases.
      However, these assays do not mimic the conditions present in normal cells and
      consequently do not assess the ability of an enzyme to function in apoptosis. In
      contrast, chromatin structure-dependent assays (nuclear autodigestion and HeLa
      nuclei assay) present intact chromatin to either endogenous or exogenous enzymes
      and assess the ability to degrade chromatin in a manner that recapitulates the
      genomic destruction seen in vivo. Detailed protocols are discussed for both
      classes of assays. These assays have been instrumental in the identification of
      several apoptotic nucleases.

PMID- 10914005
TI  - Analysis of programmed cell death and apoptosis in Drosophila.

PMID- 10914006
TI  - Analysis of programmed cell death in the nematode Caenorhabditis elegans.
AB  - The nematode Caenorhabditis elegans has been shown to be an excellent model
      organism with which to study the mechanisms of programmed cell death because of
      its powerful genetics and the ability to study cell death with single-cell
      resolution. In this chapter, we describe methods that are commonly used to
      examine various aspects of programmed cell death in C. elegans. These methods, in
      combination with genetic analyses, have helped identify and characterize many
      components of the C. elegans cell death pathway, illuminating the mechanisms by
      which these components affect programmed cell death.

PMID- 10914007
TI  - Caspase assays.

PMID- 10914008
TI  - Determination of caspase specificities using a peptide combinatorial library.

PMID- 10914009
TI  - Criteria for identifying authentic caspase substrates during apoptosis.

PMID- 10914010
TI  - Purification and use of granzyme B.
AB  - Granzyme B (GrB) is the primary molecular mediator of apoptosis by cytotoxic T
      lymphocytes (CTLs) and natural killer (NK) cells. It is a unique mammalian
      aspartic acid-cleaving serine protease. On T cell receptor activation, GrB is
      released from the CTL cytoplasmic granules by exocytosis, enters the target cells
      and, in the presence of the granule pore-forming protein perforin, it initiates
      the processing of caspases and apoptosis. GrB apoptosis is also activated by
      adenovirus, which can effectively replace perforin. Methods for the purification
      and quantitation of GrB and perforin, and the preparation and titration of
      adenovirus, are described. In addition, methods for application of these reagents
      to the initiation of apoptosis in tumor target cells, with several assays for
      detecting GrB apoptotic activity, are detailed.

PMID- 10914011
TI  - Viral caspase inhibitors CrmA and p35.

PMID- 10914012
TI  - Purification and use of recombinant inhibitor of apoptosis proteins as caspase
      inhibitors.

PMID- 10914013
TI  - Monitoring activity of caspases and their regulators in yeast Saccharomyces
      cerevisiae.

PMID- 10914014
TI  - In vitro assays for caspase-3 activation and DNA fragmentation.

PMID- 10914015
TI  - Cell-free apoptosis in Xenopus laevis egg extracts.

PMID- 10914016
TI  - Cytofluorometric quantitation of nuclear apoptosis induced in a cell-free system.

PMID- 10914017
TI  - Purification of mitochondria for apoptosis assays.

PMID- 10914018
TI  - Quantitation of mitochondrial transmembrane potential in cells and in isolated
      mitochondria.

PMID- 10914019
TI  - Nitrogen cavitation for cell disruption to obtain mitochondria from cultured
      cells.

PMID- 10914020
TI  - Apoptosis-related activities measured with isolated mitochondria and digitonin
      permeabilized cells.

PMID- 10914021
TI  - Assays for cytochrome c release from mitochondria during apoptosis.

PMID- 10914022
TI  - Purification and liposomal reconstitution of permeability transition pore
      complex.

PMID- 10914023
TI  - Monitoring interactions of Bcl-2 family proteins in 96-well plate assays.

PMID- 10914024
TI  - Analysis of dimerization of Bcl-2 family proteins by surface plasmon resonance.

PMID- 10914025
TI  - Measuring pore formation by Bcl-2 family proteins.
AB  - Two methods for assaying Bcl-2 protein family-induced solute efflux from
      liposomes have been outlined. They utilize either ion-selective electrodes to
      follow ion efflux or fluorescence to monitor changes in fluorescence of the
      liposome-encapsulated dye SPQ or carboxyfluorescein. Both methods provide a
      simple means of determining protein activity. These methods do not have the
      capability to detect either single-channel conductivity or ion selectivity, but
      they indicate whether the bulk of the protein population is inducing solute
      efflux. Although in in vivo significance of Bcl-2 protein family pore formation
      remains to be determined, in vitro measurements of channel activity should
      provide a means to determine whether a given protein preparation has activity and
      whether mutations have an adverse effect on channel formation.

PMID- 10914026
TI  - Assays for studying Bax-induced lethality in the yeast Saccharomyces cerevisiae.

PMID- 10914027
TI  - Exploiting the utility of yeast in the context of programmed cell death.
AB  - Many researchers have explored the extent to which yeast can be used to dissect
      the mechanisms of programmed cell death in higher cells. Yeast has been used as a
      system to analyze protein-protein interactions and structure-function
      relationships, and as a cloning tool to identify novel higher eukaryote
      regulators of apoptosis. In addition, classic genetic strategies in yeast have
      been used to analyze the mechanisms of action of core pathway members. The
      purpose of this chapter is to describe the strategies pursued and act as a source
      for the technical details necessary to exploit the yeast Saccharomyces cerevisiae
      and Schizosaccharomyces pombe in the context of programmed cell death.

PMID- 10914028
TI  - Production of recombinant TRAIL and TRAIL receptor: Fc chimeric proteins.
AB  - The tumor necrosis factor (TNF)/TNF receptor (TNFR) families of ligands and
      receptors are implicated in a variety of physiological and pathological processes
      and regulate cellular functions as diverse as proliferation, differentiation, and
      death. Recombinant forms of these ligands and receptors can act to agonize or
      antagonize these functions and are therefore useful for laboratory studies and
      may have clinical applications. A protocol is presented for the expression and
      purification of dimeric soluble receptors fused to the Fc portion of human IgG1
      and of soluble, N-terminally Flag-tagged ligands. Soluble recombinant proteins
      are easier to handle than membrane-bound proteins and the use of tags greatly
      facilitates their detection and purification. In addition, some tags may provide
      enhanced biological activity to the recombinant proteins (mainly by
      oligomerization and stabilization effects) and facilitate their functional
      characterization. Expression in bacterial (for selected ligands) and eukaryotic
      expression systems (for ligands and receptors) was performed using M15 pREP4
      bacteria and human embryonic kidney 293 cells, respectively. The yield of
      purified protein is about 1 mg/liter for the mammalian expression system and
      several milligrams per liter for the bacterial expression system. Protocols are
      given for a specific ligand-receptor pair, namely TRAIL (Apo-2L) and TRAIL
      receptor 2 (DR5), but can be applied to other ligands and receptors of the TNF
      family.

PMID- 10914029
TI  - Expression of lymphotoxins and their receptor-Fc fusion proteins by baculovirus.
AB  - The tumor necrosis factor (TNF) cytokine and receptor superfamily plays critical
      roles in immune physiology. Several members of this family, such as the
      lymphotoxins (LT alpha and LT beta), Fas ligand, and TNF, induce cell death in
      some normal and transformed cells, but also induce cell growth and
      differentiation. The receptors for these ligands, when expressed as fusion
      proteins with the Fc region of IgG, function as potent antagonists of biological
      activity. The receptor-Fc fusion protein is a highly versatile reagent that can
      be utilized in virtually all the formats designed for antibodies. In this chapter
      we describe the expression, purification, and assays for lymphotoxins and their
      receptors, using a recombinant baculovirus system.

PMID- 10914030
TI  - Analysis of the CD95 (APO-1/Fas) death-inducing signaling complex by high
      resolution two-dimensional gel electrophoresis.

PMID- 10914031
TI  - Measurement of ceramide levels by the diacylglycerol kinase reaction and by high
      performance liquid chromatography-fluorescence spectrometry.

PMID- 10914032
TI  - Measurement of ceramide synthase activity.

PMID- 10914033
TI  - Measurement of sphingomyelinase activity.

PMID- 10914034
TI  - Assays for JNK and p38 mitogen-activated protein kinases.

PMID- 10914035
TI  - Assaying for I kappa B kinase activity.

PMID- 10914036
TI  - Assays for Akt.
AB  - An increasing number of publications have underscored the importance of the
      serine/threonine kinase Akt in the regulation of cell survival, proliferation,
      and insulin-dependent metabolic cell responses. Critical to the understanding of
      Akt signaling in cells are experimental methods that assess its activation and
      phosphorylation state. In this chapter, we evaluate the most commonly used
      techniques to examine Akt activity. Immunocomplex kinase assays that utilize Akt
      specific substrates are described, as is the use of phosphospecific antibodies
      directed against Akt phosphorylation sites. Furthermore, we introduce coupled
      enzyme assays that indirectly measure the activity of Akt by examining the
      activity of Akt substrates.

PMID- 10914038
TI  - Volume regulation and ion transport during apoptosis.
AB  - The loss of cell volume is a defining characteristic of programmed cell death,
      which separates apoptosis from necrosis. Assessment of cell volume during
      apoptosis can easily be accomplished by flow cytometry, by examining changes in
      the light-scattering properties of living cells that are directly proportional to
      cell size and density. Flow cytometry quantitates only relative changes in cell
      size; however, when used in conjunction with Coulter (Hialeah, FL) counter
      analysis, more precise cell volume data can be obtained. Flow cytometric analysis
      of multiple characteristics during apoptosis, such as changes in intracellular
      ion concentrations, membrane integrity, and DNA content, along with changes in
      cell size, permits sorting of various subpopulations of apoptotic cells. Below,
      we describe methods for rapid examination of cell volume and ion changes during
      apoptosis.

PMID- 10914037
TI  - Measurement of cellular oxidation, reactive oxygen species, and antioxidant
      enzymes during apoptosis.

PMID- 10914039
TI  - Assays for transglutaminases in cell death.
AB  - Several in vivo and in vitro experimental model systems demonstrate a direct
      relationship between the expression and activity of tissue transglutaminase [tTG;
      also called transglutaminase type 2 (TGase 2)] and programmed cell death or
      apoptosis. This is based on mRNA and protein studies, sense and antisense
      transfection, identification of N epsilon-(gamma-glutamyl)-lysine cross-links in
      extracted apoptotic bodies, and in blue mouse experiments. In the epidermis,
      apoptosis occurs under particular conditions in the proliferative basal layer
      with the involvement of the tTG enzyme. However, in epidermal keratinocytes other
      TGases (TGase 1, TGase 3, and perhaps TGase X) are normally activated in a
      terminal differentiation program, called cornification, that leads to cell death.
      These cells perform their functions after death, providing an elastic physical
      and permeability barrier to the skin. In fact, TGase 1 mutations cause the skin
      disease lamellar ichthyosis. Because all TGases share strong similarities in
      structure and function, being involved in mechanisms of cell death, this chapter
      describes the current assays for TGases at the mRNA, protein, and enzymatic
      levels. We also describe procedures to produce, purify, and characterize
      recombinant TGases, to identify mutation in disease, to isolate cross-linked
      bodies, and to analyze the N epsilon-(gamma-glutamyl)-lysine isopeptide cross
      links. Finally, we discuss general rules for the interpretation and comparison of
      these events in cell death.

PMID- 10914040
TI  - Anoikis.

PMID- 10914041
TI  - Transient transfection assay of cell death genes.
AB  - In conclusion, transient transfection is an efficient and powerful method to
      determine quickly whether a gene has a detrimental effect on cell survival. We
      have described a variety of assay systems from which to choose. Each system has
      its own advantages and disadvantages. It is important to back up any experimental
      conclusion with more than one type of assay if possible. In addition, one must
      consider the fact that transient transfection can often achieve artificially high
      levels of a protein product that may be unrealistic in vivo. High levels of
      certain proteins may have an adverse effect on cell survival even when they have
      nothing to do with apoptosis in vivo. Thus, we must emphasize here that a
      transient transfection assay is just the first test to determine the function of
      a gene.

PMID- 10914042
TI  - Sindbis virus vector system for functional analysis of apoptosis regulators.

PMID- 10914043
TI  - Transduction of full-length Tat fusion proteins directly into mammalian cells:
      analysis of T cell receptor activation-induced cell death.
AB  - Currently, delivery of expression vectors, proteins, and/or pharmacologically
      important peptidyl mimetics to target cells is problematic because of the low
      percentage of cells targeted, overexpression, size constraints, and
      bioavailability. Concentration-dependent transduction of full-length proteins and
      domains directly into cells would serve to alleviate these problems. Previous
      researchers have demonstrated the ability of proteins linked to the human
      immunodeficiency virus (HIV) Tat transduction domain to transduce into cells; but
      because of inefficiencies, this methodological potential has not significantly
      progressed since 1988. We describe, in this chapter, a significant increase in
      transduction efficiency of proteins and ease of use by (1) generation of a Tat
      protein transduction domain in-frame bacterial expression vector, pTAT-HA, and
      (2) development of a purification protocol yielding denatured proteins. We have
      transduced full-length Tat fusion proteins ranging in size from 15 to 115 kDa
      into approximately 100% of all target cells examined, including peripheral blood
      lymphocytes, all cells present in whole blood, bone marrow stem cells, diploid
      fibroblasts, fibrosarcoma cells, and keratinocytes. Transduction occurs in a
      concentration-dependent manner, achieving maximum intracellular concentrations in
      less than 10 min. We conclude that our methodology generates highly efficient
      transducible proteins that are biologically active and have broad potential in
      the manipulation of biological experimental systems, such as apoptotic induction,
      cell cycle progression, and differentiation, and in the delivery of
      pharmacologically relevant proteins.

PMID- 10914045
TI  - Heat-shock protein 72 in human osteosarcoma: T-lymphocyte reactivity and
      cytotoxicity.
AB  - Heat-shock proteins (hsp) have been shown to be involved in tumor immunity. The
      expression of hsp72, the inducible form of the 70-kDa family, is increased in
      human osteosarcoma and correlates with a good response to neoadjuvant
      chemotherapy. It is selectively expressed on the surface of osteosarcoma cell
      lines where it acts as a target molecule for natural killer cells. Because hsps
      are strongly immunogenic, this study investigates the role of hsps as antigens in
      human osteosarcoma. Osteosarcoma cells and infiltrating T lymphocytes were
      isolated from osteosarcoma specimens from 3 patients with high-grade
      osteosarcoma. Two of the tumors immunohistochemically expressed hsp72, whereas
      one did not. T-cell lines isolated from both hsp72-positive osteosarcomas had a
      significantly proliferative response upon stimulation with recombinant human
      hsp72, whereas the T lymphocytes from the hsp72-negative osteosarcoma did not
      recognize hsp72. The lines had a significantly proliferative response upon
      stimulation with autologous osteosarcoma cells and exerted cytotoxicity.
      Cytotoxicity and proliferation could be increased by heat treatment of the target
      cell in the hsp72 responsive lines. These results demonstrate that hsp72 is
      involved in the interaction of T lymphocytes and osteosarcoma cells in a specific
      group of osteosarcomas expressing hsp72. Because of the cytotoxic potential of
      these T lymphocytes, induction of hsp72 in osteosarcomas might lead to an
      increased immune response and rejection of the osteosarcoma.

PMID- 10914044
TI  - Nasal-paranasal-oronasopharyngeal lymphomas in childhood: the role of staging
      system on prognosis.
AB  - Most of the patients with nasal-paranasal and oropharyngeal-nasopharyngeal
      (NPONP) lymphomas had early-stage disease according to the Murphy system. But the
      survival rates are not correlated with the stages. Treatment results were
      analyzed to see the effects of the staging in NPONP lymphomas. Fifty-five
      children (median age 8 years, M/F: 4.5) with NPONP lymphoma were included in this
      study. The Murphy staging system was used at diagnosis and all cases were
      restaged according to the TNM system: primary tumor, regional lymph node, and
      metastasis. The survival rates were analyzed by grouping the patients according
      to the treatment and stages. The disease was located in Waldeyer's ring, the
      sinonasal region, and the nasopharynx in 45.4, 27.3, and 27.3% of patients,
      respectively. Thirty-nine patients had stage I or II disease according to the
      Murphy system. When the TNM system was used, 92% of these patients were upstaged
      to stage III-IV. Five-year overall and event-free survival rates were 52.1 and
      50.4%, respectively, for the whole group. Five-year event-free survival rates for
      Murphy stage I, II, and III disease were 66.7, 56.9, and 45.4%, respectively. The
      rates for TNM stage III and IV patients were 64.3 and 43.8%. Treatment protocols
      were intensified in most of the early-stage disease treated with modified LSA2-L2
      regimen and better survival rates were obtained in these patients. The
      intensification of the treatment by using intrathecal treatment and doxorubicin
      in patients with early-stage disease at NPONP location seems effective. In
      conclusion, the Murphy staging system is not suitable for the staging of NPONP
      lymphomas. It should be revised to predict the prognosis and decision-making for
      treatment.

PMID- 10914046
TI  - Urine protein analysis by gel electrophoresis and laser densitometry after
      chemotherapy in pediatric cancer patients.
AB  - A common side effect of chemotherapy is reversible or nonreversible
      nephrotoxicity. SDS polyacrylamide gel electrophoresis combined with laser
      densitometry was evaluated as a suitable method to analyze pathologic urine
      proteins. A total of 52 pediatric patients were followed during and 63 patients
      were followed after therapy. During therapy renal damage was recorded in 43% of
      the leukemia patients, in 56% of nephroblastoma patients, and 75% of patients
      with other tumors. Three or more months after therapy pathologic patterns were
      seen in 25% of acute lymphoblastic leukemia patients, in 35% of patients with
      nephroblastoma, and in 62% of other patients. Patients with persistent complete
      tubular proteinuria and mixed glomerular/tubular proteinuria were found to have a
      high risk for irreversible renal damage and should be controlled periodically.
      This method permits a rapid and reliable analysis of urine proteins and is
      suitable for follow-up tests of renal function during and after chemotherapy.

PMID- 10914047
TI  - Permanent disabilities in childhood survivors of Langerhans cell histiocytosis.
AB  - This study evaluates the permanent disabilities in children treated for
      Langerhans cell histiocytosis (LCH). From January 1983 to December 1993, 50
      patients with newly diagnosed biopsy proven LCH were seen at the Regional Cancer
      Centre, Trivandrum, India. Disease pattern, treatment, survival, and disabilities
      of the patients were studied. Patients with localized disease had surgery,
      irradiation, or steroids. Patients with disseminated disease had combination
      chemotherapy. Follow-up ranged from 36 to 156 months (median follow-up 85
      months). Twelve of the 41 surviving patients (29.2%) had one or more
      disabilities. Growth retardation was seen in 8 patients, diabetes insipidus in 7,
      loss of teeth in 6, and mandibular defect, chronic aural discharge, partial
      hearing loss, facial palsy, and proptosis in 2 each. In short, a significant
      proportion of survivors of LCH had sequelae, which affected their quality of
      life. More intensive chemotherapy at the beginning might be helpful in reducing
      the disabilities.

PMID- 10914048
TI  - Ketamine anesthesia with or without diazepam premedication for bone marrow
      punctures in children with acute lymphoblastic leukemia.
AB  - Ketamine is a drug widely used for analgesia and sedation of children for
      diagnostic and therapeutic procedures. The authors investigated in a randomized
      controlled clinical trial if diazepam premedication would have a beneficial
      effect on side effects related to ketamine anesthesia for bone marrow punctures
      (BMPs) in children with acute lymphoblastic leukemia (ALL). Sixteen children 4
      years or older at the time of BMP were eligible. The first 2 BMPs after complete
      remission was obtained were studied. BMPs were performed under ketamine
      anesthesia (1.0-1.5 mg/kg i.v.), as usual. Patients were randomized to receive 1
      h before the first BMP blinded, either diazepam or placebo orally and before the
      second BMP the other way round. Blood pressure, heart rate, and oxygen saturation
      were monitored, and patients were observed for signs of anxiety, pain, and other
      side effects. The patients were interviewed after each BMP and asked for their
      preference 1 week after the second BMP. Ketamine anesthesia appeared as safe and
      effective after diazepam premedication as after placebo premedication. From the
      interviews and questionnaires, it was clear that half of the children preferred
      diazepam premedication because of less awful dreaming and more gradual falling
      asleep and waking up. Diazepam premedication may be useful for selected children
      with ALL receiving ketamine anesthesia for BMPs.

PMID- 10914050
TI  - Enteroviral meningoencephalitis in immunocompromised children after matched
      unrelated donor-bone marrow transplantation.
AB  - Two children are described who presented with fever and generalized seizures,
      days 50 and 200, respectively, after matched unrelated donor-bone marrow
      transplantation. Upon antiepileptic treatment the seizures vanished but
      somnolence and fever remained. Magnetic resonance imaging (MRI) of the brain was
      performed and revealed transient asymmetric multifocal hyperintense lesions.
      Seizures were considered related to infection, and the cyclosporin A (CsA)
      treatment was not interrupted. Enterovirus was detected by reverse transcriptase
      polymerase chain reaction in the spinal fluid of one patient and in the sputum of
      the other. Both children recovered completely within the next weeks without
      neurological sequel. This report shows that enteroviral meningoencephalitis can
      present with seizures during the post-transplant period. It highlights the
      importance of MRI for neuroimaging and of viral infections as differential
      diagnosis to CsA neurotoxicity.

PMID- 10914049
TI  - Nutritional assessment of peripheral blood stem cell transplantation in children.
AB  - Peripheral blood stem cell transplantation (PBSCT) has many advantages for
      patients because hematopoiesis and general condition return to normal more
      rapidly than they do following bone marrow transplantation. Thus, the authors
      hypothesize that the nutritional condition of patients also returns to normal
      more rapidly after PBSCT. The duration of insufficient nutrition was investigated
      in children undergoing PBSCT. The subjects of this study were 8 patients with
      malignant diseases. The factors measured were body weight, body fat, cholesterol,
      albumin, pre-albumin, and retinol-binding protein. These parameters were measured
      a day before transplantation, and then once a week for 4 weeks after
      transplantation. All parameters were recovered until day 28 from the lowest level
      in transplantation. In this study, all parameters returned to normal
      comparatively early. PBSCT causes little damage to patients' nutrition.

PMID- 10914051
TI  - Mucoepidermoid carcinoma of the bronchus.
AB  - Bronchoscopy in a 4.5-year-old girl with recurrent pneumonia showed an exophytic
      endobronchial mass. Biopsy disclosed microscopic and ultrastructural features of
      a low-grade mucoepidermoid carcinoma. Complete cure was accomplished by surgical
      removal of the tumor and right lower lobe.

PMID- 10914052
TI  - Low molecular weight heparin in the successful treatment of a spontaneous aortic
      thrombosis in a neonate.
AB  - A successfully treated case of a spontaneous aortic thrombosis in a neonate is
      described as an illustration of the advantages of using low molecular weight
      heparin (LMWH) over unfractionated heparin (UFH) for anticoagulation therapy. A 5
      day-old neonate presented with an abdominal aortic thrombosis detected by
      echocardiography. Intravenous UFH was commenced following thrombectomy. Poor
      venous access made monitoring the anticoagulation therapy problematic.
      Subcutaneous LMWH was substituted for UFH. It requires substantially less
      monitoring and no intravenous access, has fewer side effects, and allows for much
      earlier discharge from the hospital. Extensive investigation for a
      hypercoagulable state revealed no definite cause for the thrombus. The findings
      of homozygosity for a methylene tetrahydrofolate reductase (MTHFR) mutation and a
      mildly elevated homocysteine level are interesting but unlikely to account for
      the thrombotic event in this case. Anticoagulation with LMWH proved effective and
      more convenient than using UFH.

PMID- 10914053
TI  - A case with extraosseous Ewing's sarcoma: a late effect related to bone marrow
      transplantation for thalassemia or a component of a familial cancer syndrome?
AB  - Allogeneic bone marrow transplantation has proved to be a radical form of cure in
      patients with beta-thalassemia major who have a human leukocyte antigen identical
      donor. Although malignant neoplasms are serious late complications of bone marrow
      transplantation, very few reports describing the development of malignant tumors
      after allografting for thalassemia appeared in the literature. A case is
      presented here of extraosseous Ewing's sarcoma that developed 8 years after
      allogeneic bone marrow transplantation performed for beta-thalassemia major. The
      phenotypic features of the patient's family fulfill the criteria for Li-Fraumeni
      syndrome. The patient was treated with chemotherapy and radiotherapy and died
      with recurrent disease. To the authors' knowledge, this is the first case of
      extraosseous Ewing's sarcoma after bone marrow transplantation for thalassemia.
      The possible contribution of transplantation procedure and the genetic factors as
      well as the primary genetic hemoglobinopathy to the development of this malignant
      tumor are discussed.

PMID- 10914054
TI  - Squamous cell carcinoma of the tongue as a second malignancy in a patient
      previously treated for osteosarcoma.
AB  - A 15-year-old girl was diagnosed with osteosarcoma; limb salvage surgery was
      performed after preoperative chemotherapy. Postoperatively, adjuvant chemotherapy
      was given for 2 years. One year after completion of chemotherapy, the patient was
      readmitted for systemic recurrence. Amputation of the lower extremity and wedge
      resection of lung metastasis were performed followed by combination chemotherapy.
      Two years after cessation of chemotherapy, ulcer of the tongue was noted and
      cervical lymph nodes were detected by palpation. Biopsy of the lesion showed
      squamous cell carcinoma. The patient underwent a radical partial tongue resection
      and postoperative irradiation, followed by chemotherapy. Six years after
      treatment for the second malignancy, the patient remains well without evidence of
      disease. Squamous cell carcinoma of the tongue as a second malignancy after
      treatment of osteosarcoma is quite rare. Long-term follow-up, with particular
      attention to the head and neck, may be warranted in children treated for
      osteosarcoma.

PMID- 10914056
TI  - Veno-occlusive disease of the liver associated with thiopurines in a child with
      acute lymphoblastic leukemia.

PMID- 10914055
TI  - Medical management of Aspergillus flavus endocarditis.
AB  - An 11-year-old boy underwent a matched unrelated bone marrow transplant for
      refractory acute myeloid leukemia. He developed invasive aspergillus pneumonia
      and endocarditis post-transplant. The fungal endocarditis was successfully
      eradicated with liposomal amphotericin at the dose of 10 mg/kg/day. Surgical
      intervention was not required and no serious side effects of liposomal
      amphotericin were observed at this dose.

PMID- 10914057
TI  - Thrombophilia.

PMID- 10914058
TI  - Urachal tumor: an unusual presentation of neuroblastoma.

PMID- 10914059
TI  - Word for word. What we say and how we say it.

PMID- 10914060
TI  - A wrong turn. How taxonomies lead nursing astray.

PMID- 10914061
TI  - Not a terrible way to die.

PMID- 10914062
TI  - Not a terrible way to die.

PMID- 10914063
TI  - The merits of methadone.

PMID- 10914064
TI  - Troubleshooting insulin self-administration.

PMID- 10914065
TI  - The tie that binds.

PMID- 10914066
TI  - Keeping Lyme disease at bay. An integrated approach to prevention.

PMID- 10914067
TI  - Having our say. Nursing's standardized nomenclatures.

PMID- 10914068
TI  - Urinary retention. Management in the acute care setting. Part 1.

PMID- 10914069
TI  - Emergency. Adrenal crisis.

PMID- 10914071
TI  - Beyond leeches. Therapeutic phlebotomy today.

PMID- 10914072
TI  - A different kind of chest pain.

PMID- 10914073
TI  - A new code of ethics for nurses. ANA's Code of Ethics Project Task Force.

PMID- 10914074
TI  - Flex your political muscle.

PMID- 10914077
TI  - The promise and peril of electronic publishing.

PMID- 10914076
TI  - Your right to know. Chemical hazards on your unit.

PMID- 10914078
TI  - Standards and guidelines of the CAR on CD-ROM.

PMID- 10914079
TI  - Presentation of a radiation-induced soft-tissue sarcoma interpreted as a breast
      prosthesis on computed tomographic scan: case report.

PMID- 10914080
TI  - Flow-cytometry-enhanced fine-needle aspiration biopsy of the spleen.
AB  - OBJECTIVE: Flow cytometry is proving useful in the evaluation of
      lymphoproliferative disorders. In a case series, the authors investigated the
      safety of cross-sectional fine-needle aspiration biopsy of the spleen under
      sonographic guidance, and the usefulness of flow cytometry in analysis of biopsy
      samples. METHODS: Five patients underwent fine-needle biopsy with freehand
      sonographic guidance. Samples were analyzed on a flow cytometer. RESULTS: Through
      cytologic examination enhanced by flow cytometry, 2 cases of lymphoma, 1 case of
      metastatic transitional cell carcinoma, and 1 case of focal splenic hemangioma
      were diagnosed. Normal lymphocytes were demonstrated in 1 case, in which long
      term follow-up of splenomegaly showed that this was related to cirrhosis and
      portal hypertension in a patient with a history of treated non-Hodgkin's
      lymphoma. CONCLUSION: Flow-cytometry-enhanced fine-needle aspiration of the
      spleen is a safe and useful tool for the interventional radiologist. In our
      institution, it evolved as the result of effective teamwork between diagnostic
      radiologists and pathologists. Flow cytometry promises to be increasingly useful
      in the diagnosis and management of lymphoproliferative diseases.

PMID- 10914081
TI  - Arm placement of the Cook titanium Petite Vital-Port: results of radiologic
      placement in 125 patients with cancer.
AB  - OBJECTIVE: Patients with cancer require reliable venous access for therapy and
      phlebotomy. Traditionally, insertion of venous ports has been performed in the
      operating room. However, the interventional radiology service has recently become
      involved in the placement of a variety of venous access devices. This study
      examines the technique and complications associated with the placement of venous
      ports in the arm for patients with cancer. METHODS: Cook titanium Petite Vital
      Ports (Cook Canada, Stouffville, Ont.) were implanted in patients with cancer,
      and implantation was performed in the medical imaging vascular/interventional
      suite. Patients were followed prospectively by periodic chart review for a
      maximum of 42 months after port insertion. Minimum follow-up in patients who did
      not die from cancer was 6 months. RESULTS: The authors implanted 125 Vital-Ports.
      The mean duration of port implantation was 265 days (range 2 to 1278 days, total
      catheter days 33 221). Venous thrombosis developed in 5 patients (4%, or 0.06
      episodes/1000 catheter days). Four patients (3.2%, or 0.12 episodes/1000 catheter
      days) had suspected infection of the port or catheter, and 2 had culture-positive
      infection (1.6%, or 0.06 episodes/1000 catheter days). Two patients (1.6%, or
      0.06 episodes/1000 catheter days) required port or catheter revision owing to
      mechanical difficulties. CONCLUSION: The Cook titanium Petite Vital-Port,
      implanted in the arm in the medical imaging vascular/interventional suite, is
      relatively safe and effective. As a result, it has been widely accepted by the
      patients and clinicians at the hospital where this study was conducted.

PMID- 10914082
TI  - Comparison of nephrographic with excretory phase helical computed tomography for
      detecting and characterizing renal masses.
AB  - OBJECTIVE: A retrospective study was performed to compare nephrographic phase
      (NP) with excretory phase (EP) renal helical computed tomographic (CT) images
      with respect to detection of renal masses 10 mm or more in diameter, and reviewer
      confidence in mass characterization. METHODS: Two reviewers evaluated 39 renal
      helical CT examinations. All masses measuring 10 mm or more in maximal diameter
      were classified as simple cysts, complex cysts, solid lesions, or indeterminate
      lesions. Reviewers graded their confidence in the characterization of the masses
      and decided whether the NP or EP contrast-enhanced images were superior. RESULTS:
      The 2 reviewers confidently characterized 71 (reviewer 1) and 65 (reviewer 2) of
      72 detected masses 10 mm or more in diameter on NP images and 70 (reviewer 1) and
      67 (reviewer 2) of 71 detected masses on EP images. There was strong agreement
      between the 2 sets of images in respect to the characterization of renal masses
      (kappa = 1.00 and 0.86). Only one mass (a focus of acute pyelonephritis) was not
      detected by either reviewer on EP images. Collecting system artifact degraded the
      quality of the EP image in images from only 1 patient. CONCLUSION: Although EP
      images are often aesthetically inferior to NP images, use of EP images results in
      a similar rate of detection and confidence in characterization of renal masses
      measuring 10 mm or more in diameter.

PMID- 10914083
TI  - Is there a learning curve in diagnosing urolithiasis with noncontrast helical
      computed tomography?
AB  - OBJECTIVE: To report one department's experience with helical computed
      tomographic (HCT) evaluation of patients with suspected renal colic to diagnose
      ureteral calculi; to determine whether there is a learning curve in performing
      HCT in this context; and to determine whether HCT for the evaluation of renal
      colic exposes patients to more radiation than the standard intravenous
      pyelography (IVP) combined with nephrotomography. METHODS: All patients
      presenting to the emergency department with flank or abdominal pain were
      evaluated with nonreformatted noncontrast HCT. To determine changes in diagnostic
      accuracy, patients were divided into 2 groups: those evaluated between September
      1996 and January 1997 (group 1, 67 patients), and those seen from February to
      June 1997 (group 2, 53 patients). A radiation exposure study was performed using
      phantoms, and radiation exposure for HCT, IVP and nephrotomography was measured.
      RESULTS: Review of HCT scans to diagnose ureteral calculi had a sensitivity of
      91.7%, specificity of 82.6%, and accuracy of 87.2% in group 1, and a sensitivity
      of 95.5%, specificity of 86.7%, and accuracy of 91.9% in group 2. Patients
      undergoing IVP with nephrotomography were exposed to an effective dose equivalent
      of 343 mrem (dSv) (for men) and 664 mrem (for women). The effective dose
      equivalent for an HCT scan was 180 mrem. CONCLUSION: HCT offers excellent, rapid
      diagnostic accuracy without the need for intravenous contrast medium and with a
      lower radiation exposure level than IVP in evaluating patients with acute flank
      pain. There is a small but real learning curve in evaluating patients with acute
      flank pain with HCT.

PMID- 10914084
TI  - Evaluation of bone contusions with fat-saturated fast spin-echo proton-density
      magnetic resonance imaging.
AB  - OBJECTIVE: To evaluate the efficacy of fast spin-echo proton-density magnetic
      resonance imaging (MRI) with fat saturation sequences in the evaluation of bone
      contusions at the knee. METHODS: Analysis of 46 consecutive knee MRI examinations
      performed on patients referred from a sports medicine clinic after knee trauma.
      All examinations included coronal fast spin-echo proton-density fat saturation,
      fast spin-echo proton-density and fast spin-echo T2-weighted sequences. All 3
      coronal sequences were blindly reviewed independently of each other by 3
      experienced musculoskeletal radiologists to identify and grade bone contusions.
      RESULTS: Thirty-five bone contusions were identified in 24 patients. All bone
      contusions were identified on fast spin-echo proton-density fat saturation
      sequences, which was significantly greater than the percentage identified on
      either fast spin-echo T2-weighted sequences (21/35, 60%, p < 0.001) or fast spin
      echo proton-density sequences (10/35, 29%, p < 0.001). Fourteen (40%) of the
      contusions were identified only on the fast spin-echo proton-density fat
      saturation sequences. The average grade of contusion for all 35 examinations was
      also significantly higher on the fast spin-echo proton-density fat saturation
      sequences than on the fast spin-echo proton-density and fast spin-echo T2
      weighted sequences (p < 0.05). CONCLUSION: Fast spin-echo proton-density fat
      saturation sequences are more sensitive in the detection of bone contusions than
      fast spin-echo proton-density and fast spin-echo T2-weighted sequences.
      Assessment of other structures in the knee with fast spin-echo proton-density fat
      saturation MRI provides good spatial resolution and adequate T2-weighted
      information. It may have advantages over the more heavily T2-weighted fast spin
      echo T2 fat saturation and inversion recovery sequences.

PMID- 10914085
TI  - Pseudo-Argyll Robertson pupil associated with neurosyphilis: case report.

PMID- 10914086
TI  - The use of SPECT in the diagnosis of Parkinson's disease.
AB  - This article looks briefly at the latest efforts to develop an objective
      diagnostic marker for Parkinson's disease on single-photon emission computed
      tomography (SPECT). Traditionally, the diagnosis of idiopathic Parkinson's
      disease has been based on clinical criteria. However, these predict the
      pathologic diagnosis in only 80% of patients suspected of having the disease.
      Since a correct diagnosis is essential for prognosis, effective treatment and
      research, the search has continued for objective markers. The latest developments
      in nuclear medicine have come the closest in making such a marker clinically
      available. These developments are based on SPECT and positron-emission
      tomographic imaging of the basal ganglia using specific radio-labelled
      dopaminergic-receptor tracers. SPECT radiotracers target either the pre- or
      postsynaptic component of the dopaminergic system in the basal ganglia. These
      techniques show great promise in the early diagnosis of PD as well as in
      measuring its progression.

PMID- 10914087
TI  - Parvovirus B19 infection in utero--natural history and spectrum of sonographic
      manifestations in 7 cases.

PMID- 10914088
TI  - Resident's corner. Answer to case of the month #77. Segmental dilatation of the
      ileum.

PMID- 10914089
TI  - Examining the examination: Canadian versus US certification exam.

PMID- 10914090
TI  - Examining the examination: Canadian versus US certification exam.

PMID- 10914091
TI  - The influence of a workshop on dental students' perceptions about sexual
      harassment.
AB  - The objective of this study was to determine the effects of a workshop on the
      sexual harassment perceptions of students at the University of Kentucky College
      of Dentistry. Responses to a twenty-six-item questionnaire were elicited from 147
      first-through fourth-year students before and after they attended a two-hour
      sexual harassment workshop. Five questions explored students' personal
      experiences with sexual harassment; twenty-one questions addressed students'
      attitudes about sexual harassment. The repeated measures option of the SPSS
      General Linear Model statistical program was used to individually analyze the
      Likert-type scale response to the twenty-one attitude items for the following
      variables: gender, year in dental education, and whether respondents had been
      sexually harassed or had observed harassment of others. Workshop participation
      significantly changed some student attitudes about sexual harassment regardless
      of gender, year in dental education, or whether they had been harassed personally
      or had witnessed harassment of someone else (p < .05). There were also
      significant gender-related differences in the direction and magnitude of change
      in pre- versus post-workshop responses to several attitude items (p < .05).
      Workshop participants were better informed about and more sensitive to a wide
      range of sexual harassment issues. The workshop empowered students, especially
      females, to help create an environment that minimizes the probability of sexual
      harassment. This may be possible because, after the workshop, participants better
      understood institutional policies and procedures to handle complaints, including
      provisions for protection from retaliation if they do file a grievance. This
      knowledge and sensitivity may result in an environment that facilitates the
      education of beginning general practitioners who are competent, empathetic, and
      sensitive.

PMID- 10914093
TI  - A survey of neuroscience courses for predoctoral dental students.
AB  - Course directors of the seventeen neuroscience courses offered in U.S. dental
      schools were surveyed. Information was obtained about the course organization,
      topics covered, and the amount of didactic and nondidactic instruction for
      sixteen neuroscience courses, which included four courses that combined medical
      and dental student instruction. The courses averaged 51.4 contact hours with a
      range of 11 to 110 hours. Approximately 75 percent of time was for didactic
      instruction. Most courses emphasized neuroanatomy, electrochemical cell
      signaling, and the somatic sensory system, including specific lectures on pain
      sensation. The majority of courses also included several lectures on topics
      dealing with motor control and the limbic and the autonomic systems, whereas
      limited time was allocated to topics concerned with higher cortical functions.
      The nondidactic instruction typically included neuroanatomy laboratories and
      group discussions of the relation between lesions of sensory and motor pathways
      and neurological signs. The establishment of guidelines for neuroscience could
      encourage dental schools to provide a strong basic science foundation in
      neuroscience.

PMID- 10914092
TI  - A comparison of patient satisfaction among current and former dental school
      patients.
AB  - Patient satisfaction is becoming an increasingly important indicator of quality
      dental care. However, most patient satisfaction surveys target only the current
      patients of the dental practice or institution, which may give an inflated
      estimate of satisfaction with care, since dissatisfied patients are likely to
      have left the practice or institution. The purpose of this study was to compare
      the satisfaction of three categories of dental school patients with several
      aspects of care received at the school. Data were collected using a telephone
      survey of 291 patients, systematically selected from the dental school's computer
      listings of all current, recall, and former patients. The survey instrument
      sought information about why respondents came to the school for dental treatment,
      why respondents who were no longer in treatment had dropped out of care, and
      respondents' opinions on eleven aspects of quality of care provided at the dental
      school. Dental students who had completed a training session served as
      interviewers. Results indicate that, overall, patient satisfaction with the care
      received was high, with none of the means for any category of patient falling
      into the dissatisfied range. Respondents who had dropped out of care were less
      satisfied than active or recall patients in five areas: quality of care, length
      and number of appointments, treatment explanation, and fees. Results have
      implications for dental school administrators and educators in their efforts to
      provide high quality patient care and to retain an adequate patient pool to
      ensure optimal clinical experiences for students.

PMID- 10914094
TI  - Factors influencing career choice among high school students in Tanzania.
AB  - The aim of this study was to identify factors that influenced career choice among
      high school students in Tanzania. The information obtained would be used to
      formulate effective recruitment strategies and counseling students on their
      career expectations in dentistry. All 352 high school students who were studying
      in five randomly selected high schools completed a pre-tested questionnaire
      containing twenty-four items addressing five factors. Image of a profession (good
      experiences from the work of professionals, professionals who are attractive to
      respondents, and professionals who command high respect in the community) was
      perceived as an important factor in career choice by the majority of respondents
      (over 88 percent). Work/profession characteristics (knowledge about work to be
      done, treating patients, giving medicines to patients, helping relatives, etc.)
      was ranked as the second most important factor, and course characteristics
      (availability of postgraduate studies, size of annual intake, pass rate,
      geographic location, etc.) was ranked third. Direct gains and advice from
      important persons were perceived as least important in career choice.

PMID- 10914095
TI  - Preparing to be a dean.

PMID- 10914096
TI  - A profile of dental school deans.

PMID- 10914097
TI  - A program to ensure adequate clinical experience in undergraduate pediatric
      dentistry.

PMID- 10914098
TI  - Investigating Australia's burden of disease.

PMID- 10914099
TI  - Australian bat lyssavirus: the public health response to an emerging infection.

PMID- 10914100
TI  - Combating the new epidemics of chronic diseases and injuries in the Asia-Pacific
      region.

PMID- 10914101
TI  - Screening for colorectal cancer will save lives.

PMID- 10914102
TI  - Lung cancer in New South Wales: current trends and the influence of age and sex.
AB  - OBJECTIVE: To examine the effects of time, sex and age at diagnosis on lung
      cancer incidence rates and the distribution of the histological types of lung
      cancer in New South Wales. DESIGN AND SETTING: Retrospective analysis of data
      from the NSW Cancer Registry and Australian Bureau of Statistics population data
      for NSW for 1985-1995. MAIN OUTCOME MEASURES: Trends in lung cancer incidence
      rates between 1985 and 1995 for men and women aged over 30 years; changes in
      incidence rates within age groups; and incidence rates of histological subtypes
      relative to sex and age. RESULTS: The incidence of lung cancer in men aged 40-80
      years fell, while that in women aged over 65 rose. Rates were stable in younger
      women and older men. Incidence rates in men aged 40-60 years fell by 40%-60%.
      Were it not for the reduction in incidence rates in men between 1985 and 1995,
      the number of male lung cancer cases in 1995 would have been greater by 389 (95%
      CI, 362-415). In women, increasing incidence rates were responsible for an extra
      242 cases (95% CI, 232-253) in 1995. Adenocarcinoma comprised a greater
      percentage of lung cancer cases in younger people, while squamous-cell carcinoma
      increases steadily with age in both men and women. Women with lung cancer are
      less likely to have squamous-cell carcinoma (25% for women v. 40% for men) and
      therefore more likely than men to have adenocarcinoma (35% of new female cases v.
      26% for men) or small-cell lung cancer (24% v. 19%). CONCLUSIONS: Increased
      smoking cessation has seen a halving of lung cancer rates in middle-aged men.
      Whether this represents delayed or prevented cases is uncertain. The distribution
      of histological subtypes of lung cancer in women is different from that in men,
      and it is not clear whether this difference is hormone-dependent or related to
      historical patterns of smoking.

PMID- 10914103
TI  - Newborn screening for cystic fibrosis in Victoria: 10 years' experience (1989
      1998).
AB  - OBJECTIVE: To review the effectiveness of statewide newborn screening for cystic
      fibrosis (CF) in Victoria over the first 10 years of the program (1989-1998).
      DESIGN: Population study involving screening of newborns by immunoreactive
      trypsinogen (IRT) testing on Day 3-5, followed by either repeat IRT testing (1989
      1990) or delta F508 mutation analysis (1991-1998). PATIENTS AND SETTING: All
      babies screened for CF in a newborn screening program in Victoria in 1989-1998.
      MAIN OUTCOME MEASURE: The diagnosis of CF. RESULTS: Of 635,157 babies born in
      Victoria in the 10 years, 191 were diagnosed with CF. A further 30 cases were
      detected antenatally, giving an incidence of 1/2874 (95% CI, 1/2519-1/3294). CF
      was detected early in 182 babies (95.3% of affected babies in the screened
      cohort)--136 by screening, 35 because they had meconium ileus, and 11 because
      they were siblings of older children with CF. Nine cases of CF were missed by
      screening. Of these nine babies, four did not have an elevated neonatal IRT
      level, one had a normal IRT level at repeat testing at 4-6 weeks (1989-1990),
      three did not have a delta F508 mutation (1991-1998), and one had a false
      negative sweat test result. Six of the nine missed babies (67%) were diagnosed
      within four months of birth. CONCLUSION: Newborn screening for CF in Victoria has
      proven effective in detecting most babies with CF in the newborn period. However,
      a sweat test should be requested when the clinical features suggest the diagnosis
      of CF, even if the child has been screened.

PMID- 10914104
TI  - Hepatitis C prevalence among Australian injecting drug users in the 1970s and
      profiles of virus genotypes in the 1970s and 1990s.
AB  - OBJECTIVES: To examine the seroprevalence of hepatitis C virus (HCV) in the
      Australian injecting drug-using community in the 1970s, and to compare the
      profile of HCV genotypes with that seen in the 1990s. DESIGN: Investigation of
      stored sera that were collected from injecting drug users in the 1970s and
      comparison with sera collected in the 1990s. SETTING: Inner Sydney, 1974-1975 and
      1994-1996. PATIENTS: The 1970s group comprised 141 consecutive injecting drug
      users who attended the Brisbane Street Methadone Clinic. The 1990s group
      comprised 88 consecutive, injecting drug users of European origin who were HCV
      antibody-positive and attended a primary healthcare facility (the Kirketon Road
      Centre). MAIN OUTCOME MEASURES: HCV antibody prevalence (1970s); profile of HCV
      serotypes (1970s and 1990s); and serological evidence of hepatitis A and B.
      RESULTS: 84% of the 1970s group were HCV antibody-positive, of whom 92% were
      infected with HCV serotype 1 and 1% with serotype 3. In contrast, in the 1990s
      group, 69% were infected with HCV serotype 1 and 25% with serotype 3. The HCV
      positive subjects from the early group were more likely than those from the
      recent group to have serological evidence of previous HBV infection. CONCLUSIONS:
      The high prevalence of HCV among injecting drug users in the 1970s in Australia
      confirms an epidemic that has been present for at least 25 years. Over this
      period, the proportion of HCV genotype 1 infections has decreased and genotype 3
      infections have emerged.

PMID- 10914105
TI  - The Australian Burden of Disease Study: measuring the loss of health from
      diseases, injuries and risk factors.
AB  - This is an overview of the first burden of disease and injury studies carried out
      in Australia. Methods developed for the World Bank and World Health Organization
      Global Burden of Disease Study were adapted and applied to Australian population
      health data. Depression was found to be the top-ranking cause of non-fatal
      disease burden in Australia, causing 8% of the total years lost due to disability
      in 1996. Mental disorders overall were responsible for nearly 30% of the non
      fatal disease burden. The leading causes of total disease burden (disability
      adjusted life years [DALYs]) were ischaemic heart disease and stroke, together
      causing nearly 18% of the total disease burden. Depression was the fourth leading
      cause of disease burden, accounting for 3.7% of the total burden. Of the 10 major
      risk factors to which the disease burden can be attributed, tobacco smoking
      causes an estimated 10% of the total disease burden in Australia, followed by
      physical inactivity (7%).

PMID- 10914106
TI  - Australian bat lyssavirus infection: a second human case, with a long incubation
      period.
AB  - In December 1998, a 37-year-old Queensland woman died from a rabies-like illness,
      27 months after being bitten by a flying fox (fruit bat). Molecular techniques
      enabled diagnosis of infection with Australian bat lyssavirus (ABL), the second
      human case to be recognised and the first to be acquired from a flying fox. It
      must be assumed that any bat in Australia could transmit ABL; anyone bitten or
      scratched by a bat should immediately wash the wounds thoroughly with soap and
      water and promptly seek medical advice.

PMID- 10914107
TI  - Consensus guidelines for warfarin therapy. Recommendations from the Australasian
      Society of Thrombosis and Haemostasis.
AB  - The anticoagulant effect of warfarin should be kept at an international
      normalised ratio (INR) of about 2.5 (desirable range, 2.0-3.0), although a higher
      level may be better in a few clinical conditions. The risk of bleeding increases
      exponentially with INR and becomes clinically unacceptable once the INR exceeds
      5.0. Warfarin therapy should be continued for around six weeks for symptomatic
      calf vein thrombosis, and for 3-6 months after proximal deep vein thrombosis
      (DVT) that occurs after surgery or limited medical illness. Therapy for six
      months or longer could be considered for DVT occurring without an obvious
      precipitating factor, proven recurrent venous thromboembolism (VTE), or if there
      are continuing risk factors. Oral anticoagulants prevent ischaemic stroke in
      atrial fibrillation (AF). Maximum efficacy requires an INR > 2.0, but some
      benefit remains at an INR of 1.5-1.9. Patients aged over 75 years are at greatest
      risk of intracranial bleeding during warfarin therapy for AF, and the target INR
      may be reduced to 2.0-2.5, or perhaps as low as 1.5-2.0, in such patients.
      Warfarin should be withheld if it is more likely to cause major bleeding than to
      protect from stroke (e.g., in young people with isolated AF where the annual
      baseline risk of stroke is < 1%). In patients with AF, aspirin is less effective
      than warfarin (much less effective after such patients have had a stroke or
      transient cerebral ischaemia). In people with prosthetic heart valves, an INR of
      2.5-3.5 is probably sufficient for bileaflet or tilting disc valves, but a higher
      target INR is necessary for caged ball or caged disc valves. The addition of
      aspirin (100 mg/day) further decreases the risk of embolism but increases the
      risk of gastrointestinal bleeding.

PMID- 10914108
TI  - Managed care in the international context.

PMID- 10914109
TI  - Managed care--managed ethics?

PMID- 10914110
TI  - Tough on drugs--weak on tobacco.

PMID- 10914111
TI  - Why we should teach undergraduate medical students in rural communities.
AB  - In the eyes of many, the critical shortage of doctors in rural areas is the only
      reason for providing rural experiences for medical students. This article reviews
      the body of evidence supporting rural placements as a long-term medical workforce
      strategy and additional evidence regarding the apparent educational benefits of
      such placements. By enabling medical students to learn for significant periods of
      time in rural communities, it is now possible for universities to address the
      medical workforce imperatives of the communities they serve at the same time as
      providing intrinsic educational advantages to their students.

PMID- 10914112
TI  - Malaria treatment in Queensland.

PMID- 10914113
TI  - Early experience with the Diabetes Australia type 2 diabetes mellitus screening
      criteria.

PMID- 10914114
TI  - Psychogenic cough.

PMID- 10914115
TI  - The hospitalist: a third alternative.

PMID- 10914116
TI  - End-stage renal disease. Are we ready for an emerging epidemic?

PMID- 10914117
TI  - What should I do for low HDL?

PMID- 10914118
TI  - It may be fast but is it safe? Ways to protect your DSL system from hackers.

PMID- 10914119
TI  - The many forms of tremor. Precise classification guides selection of therapy.
AB  - Tremor is a common, potentially disabling symptom that occurs with a variety of
      neurologic conditions. Rational therapy is enhanced by correct identification of
      the tremor type and, when possible, of its cause. In this review, the basic
      phenomenology of tremor is presented, followed by an examination of the most
      common tremor types and their treatment. Surgical therapy for medically
      refractory tremor is discussed.

PMID- 10914120
TI  - Managing obesity like any other chronic condition. Long-term therapy may reduce
      comorbidity as well.
AB  - Patients often seek help from their primary care physician for weight loss, so
      familiarity with pharmacologic options and their risks is important. Anorexiants
      have been available for decades and are relatively safe. Orlistat and sibutramine
      are two of the newer medications that patients may have heard about in
      television, newspaper, and magazine advertising. In addition, patients often ask
      for advice regarding various herbal or nonprescription medications for weight
      loss. In this article, the authors help physicians prepare to address these
      questions.

PMID- 10914121
TI  - Management of the climacteric. Options abound to relieve women's midlife
      symptoms.
AB  - The transition out of the reproductive years can often be accompanied by
      uncomfortable and disruptive symptoms, one of the most common of which is hot
      flashes. Drs Morrissey and Kirchner describe this and other typical menopausal
      symptoms, as well as pharmacologic, hormonal, and lifestyle options that can
      bring relief and enable a smooth midlife passage.

PMID- 10914122
TI  - Facial clues to an inherited syndrome.

PMID- 10914123
TI  - Trends in end-stage renal disease. Epidemiology, morbidity, and mortality.
AB  - ESRD is always fatal unless recognized and treated appropriately. In the United
      States, the incidence of ESRD is increasing. Fortunately, both mortality among
      dialysis patients and the rate at which ESRD has been increasing over the past
      decade are declining. Obviously, the primary goal should be prevention of ESRD.
      Aggressive treatment of hypertension and hyperglycemia is likely to reduce the
      incidence of ESRD. Screening for diabetes and hypertension may be a fruitful
      approach to reduction in ESRD rates, because many patients present with renal
      failure after prolonged periods of undiagnosed hypertension or type 2 diabetes.

PMID- 10914124
TI  - Progressive renal insufficiency. Office strategies to prevent or slow progression
      of kidney disease.
AB  - Prevention of chronic renal failure should be a primary healthcare goal in the
      new millennium. Better control of blood pressure, blood glucose, and lipid levels
      shows promise for slowing and perhaps even preventing renal dysfunction. Protein
      sparing diets also may prove to be important. While it is not yet known whether
      combining interventions to treat each of these factors will have additive or
      synergistic effects, it seems prudent to approach these problems aggressively.

PMID- 10914126
TI  - Diagnosis of venous thromboembolism. Step-by-step approach to a still lethal
      disease.
AB  - Rapid diagnosis of VTE is vital in reducing the significant morbidity and
      mortality rates associated with this disease. Although angiographic studies
      remain the "gold standard" for diagnosis, many noninvasive diagnostic procedures
      are available and are appropriate for evaluation in clinically stable patients.
      The algorithm presented in this article facilitates the practical and efficient
      use of available resources in diagnosing and treating VTE.

PMID- 10914125
TI  - Renal tubulointerstitial fibrosis. New thoughts on its development and
      progression.
AB  - Current investigation of the pathogenesis of tubulointerstitial injury indicates
      that both interstitial fibroblasts and renal tubular epithelial cells promote
      extracellular matrix accumulation. Moreover, two peptides--TGF-beta and
      angiotensin II--produced locally or delivered in the circulation, appear to play
      a central role in renal fibrosis. Pharmacologic amelioration of renal fibrosis
      may require methods directed at multiple factors involved in the fibrotic
      process, including angiotensin II, TGF-beta, and the proliferation and activation
      of interstitial fibroblasts.

PMID- 10914127
TI  - High-pressure injection injury of the hand. The potential for disastrous results.

PMID- 10914129
TI  - Patient notes: Urinary incontinence.

PMID- 10914128
TI  - The genetics revolution. Ethical, legal, and insurance concerns.
AB  - Genetic researchers will soon complete a structural description of the human
      genome. Understanding of the detailed function and interactions of the genes will
      soon follow, as will the ability to manipulate genes and use them for our own
      purposes. This knowledge will force us to rethink our basic philosophy of life
      and fundamental ethics. The accumulating body of knowledge will have profound
      effects on the view of human beings in the cosmos and on human interactions and
      institutions. Although change will be gradual, primary care physicians should be
      prepared to deal with this process, even in today's practice. The crucial
      concerns are proper patient education and consent for genetic testing,
      maintenance of confidentiality, and awareness of a patient's right to access
      health insurance and specialty care. The unprecedented control of the genetic
      makeup of human beings will affect society's concepts of race, equality,
      disability, and social responsibility.

PMID- 10914130
TI  - Old age..., aging...,...

PMID- 10914131
TI  - Heart in the elderly (views and considerations at the turn of the centuries).
AB  - The proportion of elderly people grows rapidly both in Croatia and worldwide,
      posing great health care, psychological, social, economic and other problems. In
      the elderly, cardiovascular diseases, especially coronary (ischemic) heart
      diseases, account for approximately 50% of all deaths. In contrast to previous
      opinions, recent studies show that aging per se does not substantially diminish
      the efficacy of heart pump unless affected by diseases, primarily atherosclerosis
      (atherothrombosis). Atherosclerosis, however, is not an inevitable component of
      old age, but a disease that can to a great extent be prevented, and hopefully
      even defeated in the near future. Of paramount importance is elimination of the
      major risk factors: cigarette smoking, hypertension, hyperlipidemia, diabetes
      mellitus, obesity, and physical inactivity, preferably in the form of primary
      prevention, primarily by the hygienic-dietetic measures, and by medication
      (antihypertensives, hypolipidemics), if necessary. The prevention should be
      initiated early enough to prevent the development of subclinical forms of the
      disease, because clinical manifestations (angina pectoris, myocardial infarction,
      serious ventricular arrhythmias, sudden death) occurring unexpectedly ('like a
      bolt from the blue') reflect a very advanced coronary disease. The management of
      these late complications, however admirable it may be (coronary dilatation-
      stents, coronary surgery, thrombolysis, resuscitation, electrotherapy, etc.), is
      only partially successful and in fact unavailable to the majority of the
      population, even in developed countries. Therefore, every individual should be
      informed about the main characteristics of the issue to be able to take active
      participation in the programs of primary prevention. Although the relative
      importance of particular risk factors decreases in old age, these factors are
      present in a higher number in the elderly which, along with the generally greater
      mortality rate, points to the need of all measures (primary and secondary) of
      prevention to be as carefully carried out in the elderly as in younger
      individuals.

PMID- 10914132
TI  - The Zagreb method of partial laryngectomy: a retrospective study 1970-1986.
AB  - The Zagreb method of partial laryngectomy is an original method of laryngeal
      reconstruction following tumor extirpation using the sternohyoid muscle fascia.
      This material is distant from the immediate tumor site, resistant to infection,
      saliva and shrivelling, thus being very appropriate for covering major laryngeal
      defects. Statistical data analysis included clinical records from 1970, when the
      method was introduced at ENT Department, Zagreb School of Medicine, till 1986.
      During the study period, 574 patients were admitted for operative treatment of
      laryngeal carcinoma, and the partial method was employed in 350 (61%) of them.
      This percentage has generally remained unchanged to the present, because the use
      of fascia has extended the partial procedure applications and subsequent
      reconstruction. This has allowed a more extensive tumor excision without strictly
      following classical horizontal and vertical laryngectomy, with the additional use
      of so-called partial laryngectomy on demand. Records on the follow-up (5-20
      years) after this type of surgery revealed an 87% survival rate (n = 304).

PMID- 10914134
TI  - Old age and death.

PMID- 10914133
TI  - IgG serology pattern in long-term follow-up of patients successfully treated for
      Helicobacter pylori eradication.
AB  - A long-term specific IgG serology pattern after successful eradication of
      Helicobacter pylori using Pyloriset EIA-G with acid-glycine extracted antigen is
      shown. A total of 214 HP-seropositive dyspeptic patients, mean age 51, were
      included. Despite individual variability among patients, calculation of antibody
      decline in each individual, 2, 4, 6, 12, 18, and 24 months after treatment, the
      authors observed that overall mean decline in the group as a whole was 49%, 67%,
      78% 87%, 91%, and 93%, respectively. Unlike Cutler and coworkers, the authors
      found a regular constant IgG-decline in successfully treated patients until
      seroconversion. The time to reach seroconversion was found to depend on the
      pretreatment level of specific IgG. In the groups of patients with baseline IgG
      less than 1300, 42/44 (95%) seroconverted within the first year of monitoring.
      When long-term monitoring is needed, unnecessary multiple biopsies can be avoided
      by use of quantitative IgG serology.

PMID- 10914135
TI  - Natural foci of some viral zoonoses in Croatia.
AB  - Results of several-year investigations into the epidemiology and virology of
      viral zoonoses with natural foci occurring in Croatia, with special reference to
      tick-borne encephalitis (TBE) and hemorrhagic fever with renal syndrome (HFRS),
      are presented. The etiologic diagnosis of these diseases was made on the basis of
      virus isolation from patient blood and/or findings of specific antibodies in the
      serum. Several TBE and Bhanja virus strains were isolated from different species
      of ticks, and Calovo virus from mosquitoes, while the presence of Hantaan virus
      antigen was determined in the lungs of certain micromammalian species, the virus
      natural reservoirs, by direct immunofluorescence. For the largest HFRS outbreak
      in Croatia to date, which occurred in 1995 during the war, a detailed description
      is provided. The role of the geographic aspect is indicated, because an air
      corridor used by migratory birds which temporarily alight in some areas for a
      brief stop, whereby they may introduce viruses from other parts of the world,
      passes just above the territory of Croatia.

PMID- 10914136
TI  - Acute carbon monoxide poisoning as the cause of rhabdomyolysis and acute renal
      failure.
AB  - Acute renal failure (ARF) is a severe complication of acute CO poisoning which,
      combined with other organ lesions, may result in lethal outcome. In all vague
      cases of ARF with nontraumatic rhabdomyolysis, CO poisoning should be considered
      as a possible etiologic factor. The diagnosis is made on the basis of several
      simple laboratory tests: determination of carboxyhemoglobin concentration,
      demonstration of myoglobin in urine or pigment granulated cylindres in urinary
      sediment, positive orthotoluidine test, and high CPK values originating from
      skeletal musculature. Many authors report on excellent prognosis in ARF due to
      nontraumatic rhabdomyolysis of various causes. Our case report shows that the
      prognosis of CO poisoned patient greatly depends on timely and appropriate
      treatment, severity of damage to other organs, and success of the treatment of
      complications such as hospital infections.

PMID- 10914137
TI  - Aging and surgery.
AB  - Among other things, current science and civilization have enabled us to live
      longer than ever before. This, in turn, has resulted in a greater proportion of
      elderly people (aged > or = 65). In Croatia, elderly people accounted for 6.2% of
      the general population in 1971, and 11.6% in 1991. The greater proportion of the
      elderly results in increased demands placed upon the health care system,
      including surgical treatment. Due to the advances in medicine and medical
      technology, old age itself is not a contraindication for surgical treatment
      anymore. However, elderly people are more vulnerable to surgical trauma, thus
      being exposed to a higher surgical risk than young patients. Surgical risk is
      additionally increased by concomitant diseases typical for old age. Therefore,
      surgical treatment in the elderly requires strict indications. During the 1993
      1998 period, 585 elective and 286 emergency operations in elderly patients were
      performed at the General Hospital in Zabok. In patients under the age of 65,
      postoperative mortality was 1.7% after elective and 4.5% after emergency
      procedures, while in elderly patients the respective figures were 5.6% and 12.0%.
      This clearly indicates the high level of surgical risk in elderly patients
      requiring emergency operations.

PMID- 10914138
TI  - Assessment of difference between calculated and measured blood hydrogen carbonate
      concentration by anion gap.
AB  - Differences between calculated and measured hydrogen carbonate concentrations can
      pose a serious problem not only in monitoring severely ill patients, but also in
      those on hemodialysis. The purpose of this study was to investigate the
      possibility of estimation of differences between the calculated and measured
      hydrogen carbonate concentration by anion gap. The study included patients from
      regular hemodialysis program, and from Departments of Surgery, of Neurology and
      of Internal Medicine. Our results showed a 16% difference between measured and
      calculated hydrogen carbonate. Anion gap is a very useful parameter in assessing
      electrolyte disturbances. The discrepancy between the measured and calculated
      hydrogen carbonate concentration also increased with the rise in anion gap. Our
      results showed the possibility to determine the level of concentration difference
      by anion gap. This could be useful in situations such as metabolic acidosis,
      characterised by striking changes in electrolyte concentrations.

PMID- 10914139
TI  - On the history of intolerance in medical periodicals. A propos "les cafes
      vont'ils fermer?" (R. Horton).

PMID- 10914140
TI  - Creutzfeldt-Jakob disease risk in Slovak recipients of human pituitary growth
      hormone.
AB  - Creutzfeldt-Jakob disease (CJD) is a transmissible, fatal degenerative disorder
      of the CNS. CJD is known in a sporadic, familial and iatrogenic form. Iatrogenic
      form has been accidentally induced through corneal and dura mater transplantation
      or surgical procedures. The largest number of iatrogenic CJD developed in
      patients who had received human growth hormone (hGH). The minimal incubation
      period appears to be 4-15 years, the maximal 21-30 years after receiving hGh
      treatment. An increasing number of new CJD cases in hGH recipients in France,
      providing evidence of unusually long incubation period and an occurrence of
      genetically controlled (mutation E200K carrier) CJD-risk group in Slovak
      population induced this second investigation of hGh treated patients. The aim of
      this study is to verify whether the absence of CJD in hGH recipients in Slovakia
      reflects the actual epidemiological situation or a lack of informations. The
      objective of the study was to investigate signs of clinical manifestation of CJD
      and to perform molecular genetic study on prion protein (PrP) gene in hGh
      recipients. PATIENTS AND METHODS: 32 hGH treated patients (23 men and 9 women) at
      the age of 17-38 years were investigated. The occurrence of codon 200 (E200K)
      mutation and polymorphism at codon 129 of PrP gene was studied. RESULTS:
      Neurological, including cerebellar signs of CJD, intellectual or psychological
      changes were not observed in investigated patients. The shortest duration of hGH
      treatment was 2 years, the longest 9 years. The time interval since the beginning
      of hGH administration was 12-19 years. Restriction endonuclease analysis of the
      PrP gene revealed one patient with E200K mutation, 8 patients homozygous for
      methionin, 2 patients homozygous for valin and 16 heterozygous patients at codon
      129. CONCLUSION: No evidence of CJD has been observed in investigated group of
      hGH recipients. Considering the long incubation period of hGH-induced CJD and the
      obtained results, clinical and genetic investigation on the whole relatively
      small group of Slovak hGH recipients is recommended. (Tab. 2, Fig. 1, Ref. 22.)

PMID- 10914141
TI  - Heart failure development in aortic valve insufficiency.
AB  - Since left ventricle can cope well with volume overload and patients remain
      asymptomatic for years, the pharmacological interventions which prolong this
      period and inhibit heart failure development may be possible. However,
      understanding the heart failure development in chronic aortic regurgitation is a
      prerequisite. In this review currently postulated mechanisms of the slow but
      continuous development of ventricular insufficiency in chronic aortic
      regurgitation are examined. Based on this analysis the preventive competence of
      some drugs with remodelling potential is postulated: vasodilators, growth
      hormone, thyroxin analogues and carnitinepalmitoyltransferase-1 inhibitors. (Ref.
      36.)

PMID- 10914142
TI  - Contribution of thyroid gland ultrasound for screening of patients with suspected
      subclinical thyroid gland disorders.
AB  - Thyroid gland ultrasonography is recommended in patients with nonspecific
      clinical symptoms such as fatigue, weight gain, dry skin, amnesic symptoms,
      depression, bradycardia, abnormal myocardial contractility, increased diastolic
      pressure, hypercholesterolemia, menstrual abnormalities, infertility, fibrocystic
      breast disease, anxiety, insomnia, tachycardia, paroxysmal atrial fibrillation
      and osteoporosis. Subclinical hypothyroidism or hyperthyroidism can cause any of
      the above mentioned symptoms. Diffusely decreased, decreased and inhomogenous
      thyroid gland echogenicity requires laboratory examination. Thyroid gland
      ultrasonography is recommended also in patients with type I. diabetes mellitus
      and vitiligo because of increased incidence of thyroid disorders in these
      patients. Clinical observation of patients treated with Lithium, Amiodaron or
      Interferon is also recommended. (Tab. 2, Fig. 6, Ref. 18.)

PMID- 10914143
TI  - [Incidence of primary hyperaldosteronism in hospitalized patients with
      hypertension].
AB  - AIMS: To detect the incidence of primary hyperaldosteronism (PH) in hospitalized
      hypertensive patients. METHODS: Authors assessed plasma renin activity (PRA) and
      plasma aldosterone (PA) in 100 patients with arterial hypertension hospitalized
      at the II. department of Internal medicine in Kosice because of resistance to
      ambulatory treatment, eventually with the aim of differential diagnosis of
      arterial hypertension. RESULTS: From 100 hypertensive patients 90 (90%) have had
      essential hypertension (EH), 8 (8%) PH, 2 (2%) renovascular hypertension and 1
      patient (1%) pheochromocytoma. Aldosterone-renin ratio was in PH patients 10-fold
      higher comparing with EH patients. From the 8 patients with PH 4 have had adenoma
      and in 3 patients hyperplasia was diagnosed with the use of CT or histology, 1
      case was idiopathic hyperaldosteronism without CT hyperplasia evidence. In all PH
      patients the level of kalemia was less than 4 mmol/l, i.e. kalemia 4.0 mmol/l has
      100% sensitivity for PH detection. CONCLUSION: Introduction of PRA and PA
      examinations in the diagnostic process of arterial hypertension led to more
      frequent diagnosis of PH, which may probably represent the most frequent form of
      endocrine hypertension. Although ARR is a reliable test for PH screening, routine
      ARR examinations in ambulatory practice are technically complicated and connected
      with high costs. Increasing the threshold level of kalemia for PH detection led
      to higher sensitivity and that is why the authors consider ARR examination
      rational in every patient with kalemia level less than 4 mmol/l. (Tab. 4, Ref.
      18.)

PMID- 10914144
TI  - [Hypokalemic renal tubular syndromes: pathogenesis, diagnosis and therapy].
AB  - Hereditary tubular defects include syndromes with the retention of Na+,
      hypertension, hypokalemic metabolic alkalosis (Conn's and Liddle's syndromes) and
      syndromes with Na+ restriction, hypotension and hypokalemic metabolic alkalosis
      (Bartter's and Gitelman's syndromes). The understanding of their molecular
      mechanisms extended markedly with the improvement of their diagnostics,
      prevention and therapy. The paper reviews briefly their pathogenesis. (Tab. 4,
      Fig. 3, Ref. 38.)

PMID- 10914145
TI  - [Crohn's disease from the viewpoint of psychosomatic and behavioral medicine].
AB  - In a group of patients suffering from Crohn's disease increased incidence of
      affective symptoms, mainly high degree of neurosis and depressions, was detected
      with the use of psychological methods. Social relations and status may influence
      the course of the disease. Social support, information on the disease and
      patients higher educational degree have positive effects on the acceptation and
      compliance of the disease. Surprisingly negatively is the disease influenced by
      stable partnership and parenthood. Affective symptoms can be managed with the use
      of psychological methods. We proved it on reconditioning stays with structured
      programme. Their application led to reduction of neurotic and depressive
      symptoms, improvement of physical condition, better ability to relax physically
      and emotionally, the ability to harmonize psychical and physical functions, to
      cope with stress and the patients have established social contacts with other
      persons suffering from the same disease with the aim to promote conscious care of
      one's own health condition. Psycho-educational programme is extraordinary
      important in new diagnosed patients, for their ability to cope with the disease,
      and as a help for their future life arrangement. The techniques used to deal with
      stress can be helpful for prolonging the remission period. It was confirmed that
      psychological methods may contribute to life quality improvement in Crohn's
      disease patients. Self-help activities in the form of clubs and reconditioning
      stays reveal as very useful. Psycho-social intervention should become a part of
      complex care of patients with Crohn's disease. (Tab. 1, Fig. 1, Ref. 22.)

PMID- 10914146
TI  - [Immunostimulatory activity of the vaccine used in the treatment of recurrent
      urinary infections. II].
AB  - The authors describe on the immunostimulatory properties of the vaccine URVAKOL
      aimed for the treatment of recurrent urinary infections. Detection of
      immunostimulatory activity of the preparation and its effects on the humoral and
      cellular immunity were performed after oral administration of the preparation.
      Important was the evidence of nonspecific immunity of mice against intracellular
      pathogen Francisella tularensis induced with URVAKOL strain 15L. (Tab. 4, Fig. 1,
      Ref. 8.)

PMID- 10914147
TI  - [Pathology in Kosice. Its history up to the founding of a university department].

PMID- 10914148
TI  - [The Israel Teratogen Information Service: a report of the last ten years with
      20,613 calls].
AB  - The Israel Teratogen Information Service (TIS) was established 10 years ago with
      the help of the Ministry of Health and the Hebrew University-Hadassah Medical
      School. During these 10 years we have had 20,631 calls. We describe the results
      of our experience in counseling. There was a gradual increase in the number of
      calls, which in 1997 reached 4,447. Most calls (84.5%) were during pregnancy,
      while 12% were prior to pregnancy. In 75.7% the calls were due to drug exposure
      during pregnancy; 10.9% were due to exposure to X-rays; there was maternal
      infection in 6.6% and in 5% immunization during pregnancy. The callers were:
      physicians in 46.6%, nurses 18.9%, pregnant women 39.5%, and 4.8% others. In
      76.6% there was no additional risk to the embryo or fetus and in 17.4% there was
      a small additional risk of less than 1%; a significant additional risk to the
      fetus was expected in only 6%. In 3625 pregnant women with known outcome there
      were 8.9% spontaneous and 9.2% induced abortions. Of the 2968 live-born children,
      2.3% were malformed, a rate similar to that among controls. The information
      provided by the TIS alleviated the fears most pregnant women have, and reduced
      unnecessary terminations of pregnancy planned because of unjustified fear of the
      teratogenic effects of agents to which women were exposed. It reduced the number
      of children born with congenital anomalies, since pregnancies were interrupted
      whenever there was a high risk for congenital anomalies.

PMID- 10914149
TI  - [Proper use and the ability to teach the use of pressurized hand-held inhalers in
      patients with chronic airway obstruction].
AB  - Inhaling drugs via hand-held inhalers in recommended for those with chronic
      obstructive airway disease (COPD). Approximately 8%-9% of Israel's population use
      hand-held inhalers, many of them pressurized. Skill in using them and ability of
      chronic users to learn their proper use have not been assessed. During 1993 and
      1994 we studied 200 patients with bronchial asthma or COPD who regularly used a
      pressurized hand-held inhaler (PI), but were not trained to use it in our out
      patient pulmonary clinic. Only a third were found to be skilled in its use. About
      half were completely unable to use it properly, and 17% used it in a suboptimal
      way. Remarkably, only 40% had been taught anything with regard to its use. About
      75% of the suboptimal users significantly improved their skill in its use
      immediately after receiving a single individual teaching and corrective
      demonstration session. While 15% failed to learn the proper use of the PI, many
      of those who improved immediately after a single teaching session retained the
      learned skills for months. We conclude that the physician who recommends the use
      of a PI is responsible for the patient's being taught its proper use in a
      demonstration session. Skill in its use should be reassessed periodically during
      the entire treatment period.

PMID- 10914150
TI  - [The current compulsory hospitalization order and patients' rights].
AB  - Israel's "Treatment of Mentally Sick Persons Law" of 1955 was repealed and
      replaced by the "Treatment of Mental Patients Law" of 1991. Under the latter, the
      "Compulsory Hospitalization Order" (CHO) defines the new order based on
      accumulated experience with the old legislation, and on the philosophy that
      considers the CHO one of the most severely oppressive forms of deprivation of
      human liberty and rights. The new order sets limits and boundaries for CHO,
      guarding the rights of those unavoidably committed by force. According to the new
      law, the district psychiatrist decides upon and issues the order, while the
      tribunal (District Psychiatric Committee) considers appeals. The order is limited
      to 1 week, with an option for the district psychiatrist to prolong it on written
      request for up to 14 days. The tribunal can later prolong the order further. The
      objective of this study was to review changes that have occurred following
      enforcement of the new law in the Jerusalem district. A comparison was made
      between CHO's issued the year before the new legislation took effect and the year
      after. The comparison included review of all CHO's and medical files of all
      patients hospitalized by coercion during 1990 and 1992. It was assumed that there
      would be a decline in rate and length of hospitalization of patients forced to be
      committed by the new law. The main findings refuted this hypothesis. In 1992
      there was an increase of 38% in the number of compulsory hospitalizations. This
      increase derived mainly from increased demands for CHO's from psychiatric
      emergency rooms. There was also an increase in patients hospitalized by order of
      the District Psychiatric Committee using its authority under section 10(C) of the
      law. Conversely, length of compulsory hospitalization was shorter under the new
      law. In light of these findings, it would seem that the new law has only
      partially fulfilled expectations of reform in individual rights. There is need
      for further evaluation and follow-up of the CHO in order to determine whether the
      "Treatment of Mental Patients Law" of 1991 has in fact fulfilled its objectives.
      Furthermore, it is necessary to determine means, medical or legal, that may
      possibly advance further the prospective of human rights while maintaining a
      suitable balance between civil liberties and clinical needs, of over-confinement
      versus under-treatment, which may lead to neglect or danger.

PMID- 10914151
TI  - [The fate of gallstones dropped during laparoscopic cholecystectomy].
AB  - Laparoscopic cholecystectomy is considered the procedure of choice for removing
      symptomatic, stone-containing gallbladders. It is estimated that in 30-40% of
      these operations stone(s) spill into the peritoneal cavity. It was assumed that
      these "dropped stones" are harmless and are dissolved and absorbed spontaneously.
      We present a 70-year-old woman in whom such a stone, dropped during laparoscopy,
      led to formation of an intraperitoneal abscess.

PMID- 10914152
TI  - [Tension-free repair of inguinal hernia with properitoneal mesh (by the method of
      Stoppa): results and conclusions].
AB  - The results of properitoneal mesh repair of inguinal hernia were evaluated in 38
      of 43 consecutive patients operated by Stoppa's technique. In 33 patients the
      hernia was bilateral and in 10 unilateral; in 20 it was recurrent. In 33/43
      patients the mesh was fixed either by sutures or metal clips. The overall
      recurrence rate after 22 (14-36) months of follow-up, was 10.5%. This result was
      composed of a 3.0% recurrence rate in the fixated-mesh group, and 30.0% among
      those with non-fixated mesh. The outcome following the Stoppa method for tension
      free properitoneal mesh repair of inguinal hernia, compares favorably with those
      of other methods, provided proper attention is paid to adequate mesh placement
      and fixation. Further prospective studies are needed to define the role and
      indications for this technique in the laparoscopic era.

PMID- 10914153
TI  - [Traumatic aortocaval fistula].
AB  - Arterio-venous fistula is a relatively rare form of vascular injury. A case of an
      unusual fistula between aorta and inferior vena cava is presented. Occasionally
      this type of injury is difficult to diagnose early. Life-threatening conditions
      may mandate prompt treatment and the use of damage control strategy. It is also
      important to diagnose and treat this injury in order to prevent complications.
      Sudden hemorrhage and congestive heart failure are the major disturbances that
      result from aortocaval fistula.

PMID- 10914154
TI  - [Second degree atrioventricular block in Graves' disease].
AB  - Cardiac tachyarrhythmias are common in thyrotoxicosis. We report an uncommon case
      of a 53-year-old woman with Grave's disease who developed second degree A-V block
      while euthyroid on propylthiouracil. The most likely mechanism is an autoimmune
      response causing infiltration of the cardiac conduction pathways.

PMID- 10914155
TI  - [Use of abciximab (Reopro) in the catheterization laboratory and in unstable
      coronary syndromes].
AB  - Blockage of platelet glycoprotein IIb/IIIa receptor by Reopro (c7E3 Fab
      abciximab) has been shown to reduce markedly ischemic complications during and
      following elective and high-risk coronary intervention (CI). Between July '96 and
      February '98, 120 consecutive patients (85 men and 34 women, aged 34-90--mean 62)
      received Reopro (20 mg bolus, followed by 10 micrograms/min for 12-48 hours). 100
      were treated with Reopro in the catheterization laboratory, in 76 as prophylactic
      treatment preceding high-risk CI and in 24 as bailout treatment for acute
      complications during CI. 20 additional patients were treated in the CCU for acute
      coronary syndromes, 17 of whom underwent CI 6-48 hours later. Coronary
      angiography demonstrated multivessel disease in 66 (56%), and the target lesions
      were LAD--77, RCA--41, LCX--22, SVG--6, and 2 unprotected LMCA (total: 148
      lesions dilated in 117 patients). Of the 117 CI, 44 were PTCA alone, and 73
      included stenting. Indications for prophylactic Reopro for high risk CI were:
      acute MI (< or = 48 hours), early post-MI angina, unstable AP, and/or complex
      anatomy with visible thrombus. In this high-risk population the overall success
      rate (open artery, no MI, discharged alive, no need for urgent re
      vascularization) was 97% when Reopro was given prophylactically prior to CI. The
      success rate was lower (87.5%) when Reopro was given in bailout situations. In 20
      patients with acute coronary syndromes treated in the CCU while receiving maximal
      combined conventional therapy (including full-dose heparin), all symptoms and
      dynamic ischemic ECG changes disappeared within minutes following Reopro. 17
      underwent successful CI during hospitalization and 3 were treated medically.
      Reopro given prior to high risk CI was associated with a very low rate of
      complications. In a few cases with acute coronary syndromes, Reopro given in the
      CCU cases immediate relief of myocardial ischemia and reduced the need for urgent
      coronary intervention.

PMID- 10914156
TI  - [Self-limited lymphadenopathy mimicking lymphoma or lupus (Kikuchi-Fujimoto
      disease)].
AB  - Kikuchi-Fujimoto disease in a self-limited lymphadenopathy that can be confused
      histologically and clinically with lymphoma or systemic lupus erythematosus. It
      was diagnosed in a 37-year-old woman presenting with fever, cervical,
      submandibular and axillary lymphadenopathy, weight loss and recurrent urinary
      tract infections. Lymph node biopsy was consistent with the diagnosis of a
      histiocytic necrotizing lymphadenitis. Early diagnosis of Kikuchi-Fujimoto
      disease can prevent harmful treatment.

PMID- 10914157
TI  - [Nobel Prize Winner in Medicine--1998].

PMID- 10914158
TI  - [Growth hormone in the search for stature].

PMID- 10914159
TI  - [Athlete's heart, or: where is the cut off points between a healthy adaptive
      response and heart disease? Part II].

PMID- 10914160
TI  - [Another look at supracervical hysterectomy--a new approach to an old surgical
      procedure].

PMID- 10914161
TI  - [Ocular manifestations in the antiphospholipid syndrome].

PMID- 10914162
TI  - [Types of information on the Internet in injury prevention].

PMID- 10914163
TI  - [Treatment of generalized pruritus].

PMID- 10914165
TI  - [Ovarian hyperstimulation syndrome--inflammatory response?].

PMID- 10914164
TI  - [Evaluation of chest pain in the emergency room: acute myocardial perfusion
      imaging with technetium 99m sestamibi].

PMID- 10914166
TI  - [Prevention of human rabies].

PMID- 10914167
TI  - [Diseases, contagions and medicine in the Bible].

PMID- 10914168
TI  - [Low cholesterol, depression and unexplained deaths--the link and the mystery].

PMID- 10914169
TI  - [Cardiac contusion].

PMID- 10914171
TI  - [Diagnosis and treatment of heart failure within the community].
AB  - Congestive heart failure causes substantial morbidity and mortality. Symptoms and
      physical findings can help in diagnosis, but have limited sensitivity and
      specificity. Objective measurement of ventricular function is essential in
      virtually all patients in whom heart failure is suspected; reversible causes of
      heart failure must be sought. Out-patient management includes education and
      counseling, emphasis on and assessment of compliance with diet, and
      pharmacological treatment. Angiotensin-converting enzyme inhibitors are the
      mainstay of treatment but are underused, and maximal doses are not given,
      apparently because of concern about side-effects. Diuretics should be
      administered only as needed to manage fluid overload. Calcium channel blockers
      are relatively contraindicated in patients with impaired ventricular function.
      Patient follow-up should be guided by results of the medical history and physical
      examination. Routine serial testing of ventricular function and exercise
      performance is discouraged.

PMID- 10914170
TI  - [Diarrheal disease among caregivers at children's day-care centers. A
      retrospective and seroepidemiologic study].
AB  - Diarrheal disease tends to spread from infected children to their families. Due
      to the increased risk of exposure, children's caregivers in day-care centers may
      have a higher incidence of diarrhea, particularly when caring for very young
      children. We therefore examined the incidence of diarrhea and antibodies to
      Shigella among caregivers in day-care centers, according to age groups of
      children in their care (< 18, 18-34, and > 35 months) and in comparison with the
      general population. 2 studies with a retrospective cohort and seroepidemiological
      cross-sectional design were carried out. Questionnaires were completed by 401
      caregivers in 36% of all WIZO day-care centers. As a measure of past exposure to
      Shigella, levels of S. sonnei and S. flexneri antibodies were examined in the
      blood of 110 caregivers (ELISA method). There was a higher incidence of diarrhea
      among young children, increasing the potential exposure to diarrheal agents among
      their caregivers. Nevertheless, no statistically significant differences in
      diarrhea incidence were found among caregivers of the various age groups during
      the previous year (p = 0.768) and during the previous month (p = 0.319), nor in
      absenteeism due to diarrhea during the last month (p = 0.761). Levels of Shigella
      antibodies were similar among caregivers in all 3 groups. Diarrheal incidence was
      higher among women in the population control group than among caregivers during
      the previous year (p = 0.005) and month (p = 0.067). No statistically significant
      differences in levels of S. sonnei and S. flexneri antibodies were found between
      caregivers and women in the control group. There was no evidence that diarrhea is
      an occupational hazard for caregivers of young children. An explanation may be
      the development of protective immunity against common diarrheal agents due to
      recurrent exposure.

PMID- 10914173
TI  - [Ambulatory oral procedures in patients on low-dose aspirin].
AB  - Discontinuation of long-term, low-dose aspirin prior to ambulatory oral surgical
      procedures was assessed in a blind, controlled prospective study. 50 patients on
      low-dose aspirin who needed dental extractions, periodontal surgery, or other
      ambulatory oral surgery were randomly divided into test and control groups. The
      control patients stopped taking aspirin a week before operation, but in the test
      group aspirin was continued. Before, during and after surgery bleeding time was
      tested. Although bleeding time was significantly longer when aspirin was
      continued, in both groups it was within normal limits. Intraoperative hemorrhage
      was more frequent in those taking aspirin. Hemostasis control posed no problem
      and there were no postoperative complications in either group. It is concluded
      that discontinuing low-dose aspirin prior to elective oral surgery is not
      justified.

PMID- 10914172
TI  - [Meningitis due to Streptococcus bovis type II].
AB  - Meningitis due to Streptococcus bovis is rare. Only 14 cases having been reported
      in the English literature. All patients (including the patient described) had an
      underlying disease or were treated by pharmacological agents that predisposed the
      patient to the infection. Most were treated by monotherapy with penicillin G (or
      amoxicillin) and recovered. We describe a 74-year-old woman who had splenectomy
      as treatment for hairy cell leukemia 6 months before hospitalization for
      meningitis and sepsis by S. bovis type II. She was successfully treated with
      intravenous amoxicillin. There was neither evidence of endocarditis nor carcinoma
      of the colon. Although the association between S. bovis meningitis and
      endocarditis or carcinoma of the gastrointestinal tract is not well established,
      we recommend a full work-up for GI malignancy and endocarditis in every patient
      with S. bovis meningitis.

PMID- 10914174
TI  - [Diagnostic and therapeutic laparoscopy for non-palpable testis--3.5 years of
      experience at Soroko Medical Center].
AB  - From January 1994 to July 1997, 20 boys 1.5-13 years of age underwent
      laparoscopic examination and treatment for non-palpable testis. In 1 there was
      bilateral nonpalpable testis. Only 3 had intra-abdominal testes viable for
      orchiopexy. In 8 atrophic testicles were removed and in 9 laparoscopic
      examination revealed intra-abdominal blind ending of the spermatic cord and no
      testicular tissue. We conclude that laparoscopy is a useful and safe technique
      for accurate diagnosis and may avoid additional intervention in treating non
      palpable testes. Furthermore, intra-abdominal testes may be managed
      laparoscopically under the same anesthetic.

PMID- 10914175
TI  - [Atypical infantile hypertrophic pyloric stenosis].
AB  - Infantile hypertrophic pyloric stenosis (IHPS) is the most common reason for
      nonbilious vomiting in infants. Its cause is unknown. Hypertrophy of pyloric
      muscle can progress after birth and reach complete gastric outlet obstruction.
      Usually symptoms start after the age of 3 weeks. In the past diagnosis was based
      on history of projectile, nonbilious vomiting and palpation of a pyloric mass.
      Greater awareness of IHPS and increased use of imaging modalities, mainly
      abdominal ultrasonography, have resulted in a change in the clinical condition at
      presentation. The length of illness before admission has decreased and weight
      loss, dehydration and metabolic abnormalities have become less common. We
      describe an atypical clinical manifestation of IHPS: bilious vomiting. This
      atypical presentation may be due to earlier diagnosis.

PMID- 10914176
TI  - [Lymphoma of the knee joint simulating patellar fracture].
AB  - Fracture of the patella is not uncommon after direct anterior knee trauma.
      However, there are other medical situations that resemble it radiologically. We
      present a patient mistakenly diagnosed as having a patellar fracture who had
      primary, solitary, malignant B-cell lymphoma of the knee space eroding the lower
      pole of the patella. We have found no reports of such a lesion in the literature.
      Another common benign condition that might erode adjacent bone is chronic
      synovitis. Our patient was treated with chemo- and radiotherapy and the lesion
      fully regressed with no evidence of local or systemic recurrence 1.5 years after
      diagnosis.

PMID- 10914177
TI  - [Space-occupying lesions in the iliopsoas space: a challenge in the Department of
      Internal Medicine].
AB  - Mass lesions in the iliopsoas compartment (MLIPC) are uncommon in patients in
      departments of medicine and their incidence and etiologies are unclear. In a
      prospective study we diagnosed various MLIPCs in 7 patients during a 10-year
      period, representing 0.03% of admissions. Symptoms included abdominal or flank
      pain (4 cases), pain along the thigh (5), diminished psoas muscle strength (2),
      fever (2), and hypotension (1). MLIPC was suspected on clinical grounds in 5
      cases. In all cases the diagnosis was established by computed tomography (CT).
      Tissue was sampled by needle biopsy in 4 and on surgery in 1. MLIPCs were caused
      by hemorrhage (2), infection (2), neoplasia (2) and inflammatory mass (1). Often
      MLIPCs are life-threatening so their timely diagnosis by early CT scan is
      important.

PMID- 10914178
TI  - [Epidural spinal abscess].
AB  - A 42-year-old man was admitted for fever and severe low back pain radiating to
      both legs. On MRI, an epidural spinal abscess from S1 to D10 was seen. Treatment
      included laminectomy, drainage of the abscess and antibiotics. Recovery was
      complete without neurological damage. Increased awareness of this disease may
      lead to diagnosis and treatment.

PMID- 10914179
TI  - [Iatrogenic gallstone ileus as a new complication of Bouveret's syndrome].
AB  - Bouveret's syndrome involves gastric outlet obstruction caused by a gallstone in
      the duodenum. This type of gallstone ileus can be diagnosed and treated
      endoscopically. Endoscopic stone removal is especially indicated in poor risk
      patients. A dislodged impacted stone can migrate distally and cause small bowel
      mechanical obstruction. We report a 51-year-old woman who underwent endoscopic
      duodenal stone manipulation which resulted in small bowel obstruction.

PMID- 10914180
TI  - [Therapeutic goals in the treatment of hypertension in light of results and
      research on HOT (hypertension optimal treatment)].

PMID- 10914181
TI  - [Hyperhomocysteinemia--a risk factor or vascular disease?].

PMID- 10914182
TI  - [The prevalence and likelihood of sperm retrieval in the general population of
      azoospermic infertile patients].

PMID- 10914183
TI  - [Guide to renal cystic disease].

PMID- 10914184
TI  - [Non-hormonal treatment alternatives during menopause and beyond].

PMID- 10914185
TI  - [Pregnancy, childbirth and pelvic floor damage].

PMID- 10914186
TI  - [Postpartum depression].

PMID- 10914187
TI  - [The use of various diagnostic modalities for evaluation of acute torsion of the
      testis].

PMID- 10914188
TI  - [The etiology of benign prostatic hyperplasia--recent findings].

PMID- 10914189
TI  - [Dysfunctional uterine bleeding].

PMID- 10914190
TI  - [Mibefradil--a T-type calcium channel blocker].

PMID- 10914191
TI  - [The contribution of Denmark to the history to medicine and science].

PMID- 10914192
TI  - [Use of sentinel reporting clinics for influenza surveillance in the winter of
      1996-1997].
AB  - In a joint effort of the Israel Center for Disease Control, the National Center
      for Influenza in the Central Virology Laboratory, together with a group of
      collaborating pediatricians and family physicians, a network for influenza
      surveillance was established in the winter of 1996-97. Nose and throat swabs were
      obtained from 571 patients with flu-like illness. 133 (23%) were positive for
      influenza virus. Both influenza A(H3N2) and B were isolated, predominantly
      influenza B during the beginning of the season. Both circulating strains were
      antigenically similar to those included in the vaccine for 1996-1997. Patients
      from whom influenza virus was isolated were significantly more likely to suffer
      from cough and myalgia in comparison with patients whose cultures were negative
      (p = 0.02 and 0.003, respectively). Results of the first year of surveillance
      indicate that sentinel reporting clinics are useful for timely detection and
      identification of the viral strains circulating in the community, thus allowing
      prompt intervention in preventing the spread of influenza. Conclusions from the
      first year of the study were drawn and applied in the winter of 1997-1998.

PMID- 10914193
TI  - [Video-assisted thoracoscopic surgery for diagnosis of pulmonary lesions].
AB  - 23 patients (age 11-66 years) underwent video-assisted thoracoscopic biopsy for
      diffuse disease or peripheral nodular lesions of the lung. 12 had been previously
      treated for extrapulmonary malignancy and lung biopsy was done for suspicious
      metastases. In all cases except 1, lesions were identified and biopsied by
      thoracoscopy. The postoperative course was easier and shorter as compared to
      thoracotomy and the mean hospital stay was only 2.5 days. Thoracoscopic lung
      biopsy is a safe, effective and accurate diagnostic modality for diffuse lung
      disease and peripheral lesions. It is associated with minimal postoperative pain
      and discomfort, short hospital stay, early return to normal activity, and gives
      good cosmetic results.

PMID- 10914194
TI  - [Ilizarov reconstructive surgery--a solution for complex problems of the
      musculoskeletal system].
AB  - The Ilizarov technique is an important modality of reconstructive surgery for
      limb deformities, such as malunion and nonunion of fractures, persistent
      osteomyelitis, and bone loss following complex limb injuries, as well as in limb
      lengthening procedures. It has received wide recognition in the Western world
      over the past decade. In MEDLINE we found 537 articles published between 1971
      1995 that describe the use of this technique. Of these, only 18 were published
      between 1971-1975, while 261 were published between 1991-1995. The present paper
      describes the developments and updates in this method, as a result of the large
      experience gained by the authors in a number of centers in Israel using this
      technique. The Ilizarov apparatus is a circular frame that allows accurate
      control, much more than any other external fixator, during correction of limb
      deformities and limb-lengthening. It is minimally invasive, and open techniques
      and use of internal hardware and bone grafts are not needed. Based on our
      experience, we suggest that this method requires careful preoperative planning
      and meticulous surgical technique. More important, cooperation between surgeon
      and patient throughout the lengthy treatment is a prerequisite to ensure complete
      success, even in the most complicated cases.

PMID- 10914195
TI  - [Cocaine "mules"].
AB  - We present 2 cases of "body-packer" syndrome (BPS) in which the "mules" carrying
      the packages of narcotics arrived at Ben-Gurion Airport presented symptoms of
      acute cocaine intoxication due to the bursting of packages of narcotics they were
      transporting within their gastro-intestinal systems. Acute cocaine overdose due
      to sudden massive release of the drug into the digestive system in BPS, may cause
      psychosis, convulsions and eventually death. Blood levels of cocaine between 0.25
      and 5 mcg/ml are toxic and occasionally lethal. When a package bursts within the
      digestive tract of a smuggler or blocks the intestines, an immediate laparotomy
      is necessary to evacuate the "ovules" and the remains of the drug from stomach
      and intestines. Patients merely suspected of being body packers can be diagnosed
      by physical examination and by means of various imaging methods. They can be
      conservatively treated with fluids and mild laxatives and kept under close
      supervision until the remaining packages are naturally discharged. Sudden onset
      of psychotic behavior in travelers from South America or other drug-producing
      countries should raise suspicion of body-packer syndrome. The relevant
      authorities should therefore be aware of the symptoms and consider their
      potentially dangerous outcome.

PMID- 10914196
TI  - [Maximal age of patients as a reflection of health neglect of the geriatric
      population].
AB  - In publications relating to the health of the elderly there are 2 ways of
      presenting maximal ages, collective (for example: 70+ years) and individual
      maximal age (for example 70 years). While enabling assessment up to a certain
      age, data from subjects above the maximal age stated in the research will not be
      included. From the literature of the past 10 years, there were selected 764
      disease parameters (PD) and 177 parameters of aging (PA). Among them 667 (70.9%)
      and 274 (29.1%) were parameters with collective and exact maximal ages,
      respectively. The lack of reference by authors to ages above 70 to 79 (or 70+ to
      79+) and 80 to 89 (or 80+ to 89+) was calculated from the medical literature, and
      estimated as significant, and for ages above 80 to 89 was estimated as minimally
      significant, in regard to their focus on health data in the elderly. In different
      groups of parameters, 24% to 32% of maximal ages indicated significant and 25% to
      65% minimal lack of reference. Maximal ages of PA were higher than those of PD (p
      < 0.001), so lack of reference to health of the elderly was more significant when
      PD were studied as compared to PA. Lack of reference was more significant in
      studies of hospitalized and ambulatory patients and people living within the
      community. Usually authors checked all the populations of people living in
      nursing homes, but the total number of parameters relating to the latter, was
      very small, only 5.1% of the total number of parameters, so the populations of
      nursing homes did not reach the attention of the researchers. Collective maximal
      ages are more often used in geriatric journals, including the Journal of the
      American Geriatric Society, as opposed to general and gerontological journals,
      although this approach seems to be too sweeping in the assessment of health of
      the elderly.

PMID- 10914197
TI  - [Percutaneous closure of patent arterial ducts with occluding spring coils].
AB  - In recent years percutaneous closure of small and medium-sized patent arterial
      ducts has been achieved using occluding spring coils. We describe our experience
      in 93 patients with this technique, using a snare to facilitate the procedure in
      most. All patients had a clinically apparent patent arterial duct and had
      undergone attempts at transcatheter closure at a mean age of 6.8 years. In 1, the
      duct was a residual lesion following surgical ligation, and in 5 it was a
      residual following attempted closure with the Rashkind double-umbrella. The mean
      narrowest diameter of the ducts was 2.1 mm. In our 93 patients implantation was
      successful in 92 (99%), using 1 coil (82 patients), or 2 (10 patients), and in 1
      by a combination of a double-umbrella device and an occluding spring coil. The
      mean fluoroscopic screening time for the whole group was 22.8 minutes, which
      decreased to 16.8 minutes in the last 50 patients. The coil embolized in 7
      patients, but was retrieved in 6 and the ducts were subsequently occluded with
      another coil. In 1 patient the coil was left in a distal small branch of the left
      pulmonary artery and the duct was successfully occluded with a double-umbrella.
      Color-Doppler echocardiogram performed the morning after placement of the coils
      showed residual leaks in 18%. At mean follow-up of 24.6 months repeat imaging
      showed residual leaks in only 3 of these patients (3%). We conclude that
      occlusion of small to medium-sized ducts using coils appears to be effective and
      is the treatment of choice. The use of a snare to hold and manipulate the coil as
      it is delivered improves control of the coil, the accuracy of its placement, as
      well as giving complete occlusion of the ducts.

PMID- 10914198
TI  - [Alcoholic delirium: warning signs and diagnosis].
AB  - Lately an increasing number of physicians are asked to diagnose and treat
      physical and mental disorders caused by alcohol abuse, a phenomena which had been
      quite rare in Israel until recently. Early diagnosis and efficient treatment are
      essential for the management of alcohol-dependent patients. Primary care
      physicians and hospital personnel should be more alert to the growing numbers of
      alcohol abusers and to their appropriate diagnosis and treatment. This article
      describes and summarizes the symptoms of alcohol withdrawal in general, and
      alcoholic delirium in particular. Problems in diagnosis and treatment are
      illustrated by typical cases, pointing out early clinical warning signs and
      suggesting some treatment guidelines.

PMID- 10914199
TI  - [Cerebellar infarction, clinical presentation, diagnosis and treatment].
AB  - Cerebellar infarction is relatively infrequent and accounts for about 2% of all
      strokes. Its clinical presentation and course are variable. It may resemble
      vestibulitis in mild cases, but the presentation may be more dramatic in other
      cases. Cerebellar infarction may cause life-threatening complications such as
      acute hydrocephalus or brain stem compression, resulting from their mass effect
      in the posterior fossa or extension of the infarct to the brain stem. Clinical
      features alone are insufficient for the diagnosis and for follow-up of patients
      with cerebellar infarction. However the advent of CT and MRI and their
      availability enable early diagnosis of cerebellar infarction, and early
      recognition of the development of acute hydrocephalus or brain stem compression
      which require surgical decompression. The prognosis of most cases is good when
      treatment is appropriate.

PMID- 10914200
TI  - [Acute appendicitis--the end of innocence?].

PMID- 10914201
TI  - [Treatment of sarcoidosis--1999].

PMID- 10914202
TI  - [Dialysis patients and cyclosporine-treated graft recipients: two sectors with
      high homocysteine levels].

PMID- 10914203
TI  - [Transverse vaginal septum--diagnosis and treatment].

PMID- 10914204
TI  - [Upper extremity deep vein thrombosis].

PMID- 10914205
TI  - [Prophylactic antibiotics in orthopedic practice. Part I: Clean orthopedic
      surgery and joint replacement surgery].

PMID- 10914207
TI  - [Delusional disorders as seen by the court].

PMID- 10914206
TI  - [Occult bacteremia in children--an old syndrome, new approaches].

PMID- 10914208
TI  - [Osler-Weber-Rendu syndrome].

PMID- 10914209
TI  - [From the Holocaust. The lst journey of Janusz Korczak].

PMID- 10914210
TI  - [Sheba, Alterman, Ben-Gurion and pediatrics].

PMID- 10914211
TI  - [Legionellosis in Israel--a view of the situation].
AB  - Infection with Legionella remains an important cause of disease and death. We
      analyzed our laboratory data from 1993 through 1997, augmented by our 20 years of
      experience. The incidence of Legionella as a cause of pneumonia varied in our
      study from 5%-9%, with a slight increase during the winter. Isolation of these
      microorganisms from different water sources was higher during the summer and
      ranged from 7%-70%. Special laboratory tests are necessary to diagnose the
      disease and monitor these bacteria in water samples. The serologic method-
      indirect immunofluorescent assay--for 41 serogroups of Legionella was the main
      diagnostic method used. Legionella sg. 1 was the most frequent cause of the
      disease, with an incidence of 52% in 1993, decreasing to 15% in 1997. An increase
      in the incidence of seropositivity to "other Legionellae" is characteristic for
      our country. No correlation was found between the incidence of isolation of a
      specific strain and exposure. However, it is well known that the disease is
      overtreated but underdiagnosed, which requires reversal. Larger studies of
      Legionella colonization in water supplies and in air are needed in order to
      establish the risk of infection. Water sources are presently under-studied, as
      are respiratory devices in hospitals, or they are not studied at all in Israel,
      such as in mist machines in supermarkets, in dental clinics, and in ships and
      airplanes.

PMID- 10914212
TI  - [Intestinal transplantation--world experience and future perspective].
AB  - Intestinal transplantation, which until recently has been considered an
      experimental procedure, is now undergoing considerable change and becoming a
      standard treatment for patient with intestinal failure. The major improvement in
      results is due to the introduction of new immunosuppressive agents that have led
      to significant reduction in acute rejection. Nevertheless, reduction in severe
      infectious complications, which are the main cause of mortality after transplant,
      as well as improved techniques for early diagnosis of rejection are needed before
      intestinal transplantation can be widely used. We describe our experience in post
      transplant follow-up of a woman, aged 32-years, who had undergone intestinal
      transplantation for short bowel syndrome after extensive bowel resection.

PMID- 10914213
TI  - [Laparoscopic repair of inguinal hernia--experience in 54 consecutive cases].
AB  - We describe our experience in 54 consecutive patients who underwent laparoscopic
      repair of 86 inguinal hernias. Laparoscopic repair of inguinal hernia is
      technically feasible, does not prolong the length of the procedure nor of
      hospitalization and is not accompanied by increased morbidity. Although there is
      not yet general agreement, in our experience and that of others, it appears that
      laparoscopic repair will be the preferred approach to the treatment of inguinal
      hernia.

PMID- 10914214
TI  - [Combination chemotherapy with M-VAC protocol in metastatic urothelial cancer].
AB  - The treatment of metastatic urothelial cancer is based on the combination of
      cisplatin, methotrexate, vinblastine and adriamycin (M-VAC). From November 1994
      to May 1997 we treated 25 patients (51 men, 3 women, aged 50-77) with M-VAC. The
      tumor originated from the urinary bladder in 14 (56%) and the upper urinary tract
      in 11 (44%). Disease sites included: primary--5 (25%), lymph nodes--17 (68%),
      lungs--10 (40%), bones--8 (32%), pelvic mass and liver each--4 (16%), with an
      overall median of 2 (1-5) sites per patient. 9 patients (38%) had complete
      responses and 8 (32%) had partial responses, for an overall response rate of 68%
      (95% CI 48.5%-85%). The median duration of response was 15.3 (1.6-29.6+) months.
      Median survival of responders was 19.1 (4.8-35.7+) months compared to 6.2 (0.7
      11.2) for the non-responders (p < 0.05). 13 (52%) of patients are alive, of whom
      8 (32%) are free of disease and 5 with a single metastatic site on presentation
      at follow-up. In the 118 treatment cycles we observed grade III-IV toxicity:
      myelosuppression 53 (45%), thrombocytopenia 4 (3%), stomatitis 8 (6.7%), diarrhea
      3 (2.5%). There were 22 infectious episodes and 1 patient died of sepsis. We
      achieved a high response rate with the combination M-VAC. However, only a third
      had long-term disease-free states and treatment was associated with excessive
      toxicity. Therapeutic approaches with new agents are required to improve the
      response rate and toxicity.

PMID- 10914215
TI  - [Multisystem disease caused by BCG imitating miliary tuberculosis].
AB  - As the prevalence of tuberculosis is on the rise in western countries, we present
      a 79-year-old man who developed a pulmonary tuberculosis-like syndrome following
      immunotherapy with BCG for carcinoma of the urinary bladder. The symptoms
      subsided following 3-drug antitubercular treatment, and the addition of steroids
      following negative cultures for Mycobacterium tuberculosis. The course of this
      disease, named BCG-osis, is much more favorable than miliary tuberculosis, even
      with milder treatment. It is important to keep in mind this phenomenon now that
      there is increasing treatment of cancers with BCG.

PMID- 10914216
TI  - [Muir-Torre syndrome and HNPCC: importance of clinical diagnosis and genetic
      investigation in family members].
AB  - Muir-Torre syndrome is a relatively rare cutaneous manifestation of hereditary
      nonpolypous colorectal cancer (HNPCC). This autosomal dominant syndrome is
      characterized by a combination of sebaceous gland and malignant visceral tumors.
      The common sites of internal malignancies are the gastrointestinal tract and
      urinary system. It appears in early adult life and its clinical course is
      relatively slow. In some families genetic diagnosis can identify asymptomatic
      carriers of the mutation. All first-degree relatives, especially mutation
      carriers, should be referred from the age of 20 years for routine follow-up and
      early treatment, as it has been proven to decrease morbidity and mortality. We
      present a 51-year-old man with Muir-Torre syndrome diagnosed by the presence of
      multiple adenomas of sebaceous glands, colonic adenoma and adenocarcinoma of the
      duodenum. The family history was typical for HNPCC. A mutation in the hMSH2 gene
      on chromosome 2p was found in the patient and in several asymptomatic family
      members. The aim of this report is to increase awareness of this syndrome and
      emphasize the importance of referring patients and their families for clinical
      and genetic counseling and diagnosis.

PMID- 10914217
TI  - [Brucellosis presenting as acute abdomen].
AB  - Usually symptoms of brucellosis are nonspecific and characterized by a wide range
      of complaints. Although the disease in Israel is almost exclusively food borne
      (caused by Brucella melitensis in unpasteurized goat milk products) so the main
      route of infection is the gastrointestinal tract, but gastrointestinal
      complications are rare, and only sporadic cases of ileitis or colitis have been
      described. We present a 43-year-old woman with an acute abdomen, probably due to
      diverticulitis. It was diagnosed only after blood cultures were positive for
      Brucella melitensis. We believe that its protean manifestations should be
      considered in addition to the other bizarre presentations of this disease,
      important in our region.

PMID- 10914218
TI  - [Ramsay Hunt syndrome--differential diagnosis, pathogenesis and therapy].
AB  - Ramsay Hunt syndrome is caused by infection of the geniculate ganglion of the
      seventh cranial nerve by varicella-zoster virus. A case in an 82-year-old woman
      is described. She presented with oral lesions, right facial palsy and an eruption
      and pain in her right ear. Oral examination revealed small circumscribed erosions
      on the right anterior two-thirds of the tongue, with loss of taste. There were
      also lesions on her right palate. Early diagnosis and treatment are important as
      immediate treatment is more likely to prevent irreversible complications
      affecting the facial and other cranial nerves involved.

PMID- 10914219
TI  - [The X-ANCA antibodies--importance and clinical significance].

PMID- 10914220
TI  - [Fixing a failing heart: molecular and cellular approaches].

PMID- 10914221
TI  - [Depression and the immune system].

PMID- 10914222
TI  - [The rational and reality: between chaos and utopia].

PMID- 10914223
TI  - [The management of hypertensive crisis].

PMID- 10914224
TI  - [Childhood obesity--a weighty problem].

PMID- 10914225
TI  - [Interstitial cells of Cajal--the pacemaker of the gastrointestinal system].

PMID- 10914226
TI  - [Abdominal wall pain caused by cutaneous nerve entrapment].

PMID- 10914227
TI  - [Prophylactic antibiotics in orthopedic practice. Part II: Closed and open
      fractures].

PMID- 10914229
TI  - [Are health workers a source of infection in the hospital?].

PMID- 10914228
TI  - [Sterilization and use of sterile products in hospitals and disinfection of the
      air by hydrogen peroxide].

PMID- 10914230
TI  - [Talmudic lipectomy].

PMID- 10914231
TI  - [Physicians and medicine in Moliere's plays].

PMID- 10914232
TI  - [Preliminary report of experience with laparoscopic splenectomy in adults and
      children].
AB  - Laparoscopic splenectomy is effective and technically feasible for treating
      various hematological diseases such as idiopathic thrombocytopenic purpura (ITP),
      congenital spherocytosis, hemolytic anemia, and Hodgkin's lymphoma. An anterior
      approach to the vascular pedicle is usually described. However, in this approach
      to the splenic hilum, the dissection of the splenic artery is frequently
      difficult. The laparoscopic posterolateral approach involves dissection of the
      posterolateral attachments to the diaphragm, followed by the dissection and
      ligation of all splenic branches near the splenic parenchyma. We used it in 9
      adults and 4 children: 11 patients had ITP, 1 spherocytosis and 1 Hodgkin's
      lymphoma. This procedure was completed in 13 patients, but in 2 it had to be
      converted to open surgery. Mean operating time was 3 hours and mean postoperative
      stay 3 days. Blood transfusion was not required and there were no postoperative
      complications. Laparoscopic splenectomy is safe in both adults and children, and
      the posterolateral approach provides excellent visualization and allows control
      of the branches of the splenic vein and artery in the splenic hilum.

PMID- 10914233
TI  - [Operative laparoscopy in pregnancy].
AB  - The development of laparoscopic surgery in gynecology and general surgery has
      greatly advanced over the past decade, and recently has been successfully
      performed in pregnancy. In the English literature we found that of the 518 cases
      reported (mean age 32 years) the most common was for cholecystectomy (45%),
      followed by operations on the adnexae (34%), appendectomy (15%) and others (6%).
      To these we add 3 cases of cholecystectomy and 1 of an adnexal tumor. Of all the
      reported cases, 33% were performed in the 1st trimester, 56% in the 2nd and 11%
      in the 3rd. This review demonstrates a definite trend to laparoscopy in
      pregnancy. It appears to be safe when performed by experienced surgeons, but
      further studies addressing safety of laparoscopic surgery during pregnancy are
      needed to reach definitive conclusions.

PMID- 10914234
TI  - [D-lactic acidosis in short bowel syndrome].
AB  - A boy of 20 months and a girl of 27 months who had previously undergone massive
      bowel resection due to congenital intestinal obstruction are described. During
      gradual reduction of total parenteral nutrition and initiation of oral feeding,
      both developed severe, acute metabolic acidosis, accompanied by encephalopathy
      and ataxia. After the laboratory identification of massive amounts of the d
      isomer of lactic acid in urine and blood, both were successfully treated with
      i.v. bicarbonate, and metronidazole to suppress the overgrowth of colonic
      lactobacilli responsible for the metabolic crisis.

PMID- 10914235
TI  - [Quality assurance in the mental health department of the Israel Defense Forces].
AB  - A review of quality assurance in the mental health department of the Israel
      Defence Forces allowed the examination of certain unique elements of quality
      control which pertain to the military. These include the psychiatric medical
      board, the computerized documentation of appointments and sessions with soldiers,
      the psychiatric hospitalization database, control systems implemented in the
      draft boards, peer-review boards and supervision, and a special officer in charge
      of handling outside consultations and queries. There were other components of
      quality assurance and control as well. These instruments are vital in a dynamic
      system constantly striving to improve clinical performance. Future plans include
      the continued use and expansion of quality control boards, the inclusion of
      quality assurance in the curriculum of mental health officers, and the use of
      clinical guidelines in working with soldiers. All of this is in keeping with the
      principle of continuous quality improvement, with the aim of viewing the soldier
      in need of help as a client.

PMID- 10914236
TI  - [Nerve palsies in a soldier with penetrating injuries following prolonged use of
      limb tourniquets].
AB  - Nerve paralysis following the use of tourniquets, regular or pneumatic, for limb
      surgery is rare. We describe a 19-year-old male soldier who had tourniquets
      applied for 3 1/4 hours to his arm and both legs due to penetrating injuries. As
      a result, he suffered palsy of the radial nerve and both common peroneal nerves.
      Nerve palsy in such cases has not been described in the literature. It is not
      clear whether the cause is direct mechanical pressure on the nerve, nerve
      ischemia, or a combination of both. We recommend that tourniquets should not be
      used continuously for more than 2 hours. If evacuation of the injured is delayed,
      the medical team should consider loosening tourniquets for short intervals or
      changing for a pressure bandage. This is providing the patient's condition is
      stable and bleeding does not start again on release of the tourniquet.

PMID- 10914237
TI  - [Exhaustion of motor cortex after head injury--revealed by transcranial magnetic
      stimulation].
AB  - We evaluated the pattern of motor evoked potentials elicited by single-pulse and
      slow-rate (1 Hz) repetitive, transcranial, magnetic stimulation (RTMS) in minor
      head injuries. The motor response to a single magnetic stimulus in patients with
      minor head injury was characterized by a significantly higher threshold than in
      healthy subjects. However, central and peripheral motor conduction was normal in
      all patients. A stable pattern of MEP throughout the RTMS session was the most
      prominent feature in the control group. A progressive decrease in MEP amplitude
      and irregular alternation of large and very small MEPs over the course of RTMS
      was observed in minor head injury. The higher threshold of the motor response and
      the abnormal patterns of MEP behavior revealed by RTMS may reflect impaired
      excitability and enhanced exhaustion of the motor cortex in patients with minor
      head injuries, which improve with time.

PMID- 10914238
TI  - [Tension-free "plug and patch" inguinal hernia repair].
AB  - Inguinal hernias are common and have highly variable clinical presentations,
      ranging from the asymptomatic to surgical emergencies when incarcerated,
      sometimes necessitating bowel resection. Several techniques have been described
      for repair of inguinal hernias based on the unique anatomic structure of the
      inguinal region. In 1989 Lichtenstein and co-workers described a "tension free"
      repair based on using a synthetic mesh patch to reinforce the inguinal canal
      floor and as a plug to prevent recurrence through the internal inguinal ring.
      This technique has been used in many centers worldwide with good rates of
      success.

PMID- 10914239
TI  - [Danaparoid sodium for dialysis in heparin-associated thrombocytopenia].
AB  - Danaparoid sodium is an antithrombin composed of 3 glycosaminoglycans: heparan
      sulfate, dermatan sulfate and chondroitin sulfate. Similar to heparin, danaparoid
      operates by activating antithrombin 3, but does not contain heparin or heparin
      fragments, and is therefore antigenically distinct. Danaparoid has been advocated
      as a safe and effective anticoagulant for heparin-associated thrombocytopenia.
      However, there is little experience in its use as a substitute for heparin in
      hemodialysis. We report 2 men, aged 82 and 73 years, respectively, who developed
      thrombocytopenia while undergoing hemodialysis with heparin, and who subsequently
      underwent successful dialysis with danaparoid. There was a rise in platelet
      levels in both while receiving danaparoid, and dialysis was completed without
      hemorrhagic or thrombotic complications. Danaparoid is a safe and effective
      substitute for heparin, and may be used as an anticoagulant in hemodialysis.

PMID- 10914240
TI  - [Portal and superior mesenteric vein thrombosis after splenectomy for idiopathic
      thrombocytopenic purpura].
AB  - Mesenteric and portal vein thrombosis are rare complications of splenectomy.
      Their presentation depends on the underlying disease. It is most frequent in
      lymphoproliferative disorders but extremely rare in trauma. We describe a 22-year
      old man and a 49-year-old woman who underwent splenectomy for idiopathic
      thrombocytopenic purpura and developed mesenteric and portal vein thromboses.
      Both were treated successfully with anticoagulants for 3 months until the thrombi
      regressed, as shown by CT scan. During a year of follow-up they were
      asymptomatic.

PMID- 10914241
TI  - [The "wandering spleen" syndrome].
AB  - We describe a 26-year-old woman with thrombocytopenia discovered during
      gestation. On admission for evaluation of abdominal pain, torsion of an ectopic
      spleen was found. The spleen was removed and the thrombocytopenia resolved.

PMID- 10914242
TI  - [Neurological manifestations of non A-G viral hepatitis].
AB  - Guillain-Barre and other neurologic syndromes rarely occur as complications of
      viral hepatitis (A, B and C). Other neurologic syndromes have also been reported
      in serologically defined viral hepatitis, including mononeuritis, auditory
      neuritis, and seizures. Chronic hepatitis B and mononeuritis multiplex are found
      together in 31-54% of patients with periarteritis nodosa. The mechanisms of these
      associations are unknown, but may include direct cytotoxicity of the virus or
      immune-mediated damage. Vasculitis of the vasa nervorum plays an intermediate
      role, at least in some cases. We describe a 36-year-old man with acute non A-G
      hepatitis complicated by Guillain-Barre syndrome. The neurological manifestation
      resolved completely without specific therapy within 6 days, as the hepatitis
      resolved.

PMID- 10914243
TI  - [Tetracyclines: fifty years of success].

PMID- 10914244
TI  - [Practical guide for peak expiratory flow monitoring in asthmatic patients].

PMID- 10914245
TI  - [Physical exercise as therapy for obesity in children and adolescents--the effort
      pays off].

PMID- 10914246
TI  - [Natriuretic peptides--is it time for clinical use?].

PMID- 10914247
TI  - [Sharp increase in incidence of syphilis in the former Soviet Union--a cause for
      concern in Israel?].

PMID- 10914248
TI  - [Retinopathy of prematurity].

PMID- 10914249
TI  - [Autoimmune phenomena following minocycline treatment].

PMID- 10914250
TI  - [The diabetic foot].

PMID- 10914251
TI  - [Hepatic injury associated with use of nitrofurantoin].

PMID- 10914252
TI  - [Aspects of nutritional therapy in Crohn's disease].

PMID- 10914253
TI  - [Dr. Moscovitz, the physician of the Rehovot colony in the years 1910-1916].

PMID- 10914254
TI  - [129 liver surgeries--five years of experience in a surgery department].
AB  - Major hepatic resections have been associated with significant morbidity and
      mortality. In the past decade or so this has changed and such procedures are now
      done in increasing numbers. In the past 5 years we operated on 129 patients with
      benign or malignant hepatic lesions (75 females, 54 males; age-range 14-84). The
      reason for surgery was malignancy in 94 (72.9%) and benign lesions in 35 (27.1%).
      The most common indication for surgery was liver metastases secondary to
      colorectal cancer in 45% of all patients or 61.7% of those operated for
      malignancy. Primary liver cancer was the cause for liver resection in 13.2% of
      all patients or 18.1% for those with malignancy. Of the 35 patients with benign
      lesions the leading causes for surgery included: giant cavernous hemangioma,
      simple liver cysts, echinococcus cysts and focal nodular hyperplasia (11%, 22.8%,
      20% and 14.3%, respectively). 76 patients underwent anatomical resection and 63
      had either a nonanatomical resection or a different operation. Among the former
      the most common procedure was right hepatectomy (36) and among the later a
      nonanatomical resection equal to 1-3 Couinod segments (44). Operating time ranged
      from 55 min. to 8:41 hours with a mean of 3:31 +/- 1:37. Mean hospital stay was
      8.7 +/- 5.8 days and 86.8% received between 0-2 units of blood. Overall mortality
      was 6.2% and 31.2% of the fatalities had cirrhosis. Overall mortality in
      noncirrhotic patients was 2.6%. The complication rate was 16.3% and only 7
      patients (4.4%) were hospitalized in the intensive care unit. This indicates that
      major liver resections can be done safely, with morbidity and mortality similar
      to that of other major abdominal operations.

PMID- 10914255
TI  - [Balloon angioplasty of native coarctation of the aorta].
AB  - The use of balloon dilatation to treat native coarctation of the aorta is gaining
      acceptance among interventional pediatric cardiologists, but is still
      controversial. We describe our experience with this procedure in 21 children,
      mean age 5.6 years and mean weight 21.1 kg. Most had an additional congenital
      heart defect, most commonly a bicuspid aortic valve. 17 were asymptomatic, 3 had
      tachypnea and 1 infant had severe congestive heart failure and was ventilated.
      The mean systolic blood pressure was 129.7 mm Hg. Balloon dilatation was
      successful in 90% (19), decreasing the mean maximal systolic gradient from 35.3
      to 9 mm Hg (p < 0.001), and increasing the narrowest area from 3.9 to 8.2 mm (p <
      0.001), with a mean balloon-to-coarctation width-ratio of 2.8. There were no
      complications. Of 15 who underwent repeat cardiac catheterization at a mean
      interval of 10.6 months, 2 had a maximal systolic gradient of more than 20 mm Hg.
      1 of these underwent successful repeat angioplasty and the other, who also had a
      small aneurysm, underwent surgical repair successfully. 2 others had small
      aneurysms and they are being followed clinically. All patients were seen again
      after a mean interval of 31 months. The mean systolic blood pressure was 104 mm
      Hg, significantly lower than before intervention (p < 0.002). 1 had an increased
      pressure gradient between right arm and leg of 35 mm Hg at later follow-up, and
      repeat cardiac catheterization demonstrated a good result 13 months after the
      initial procedure. She is awaiting a third catheterization. Overall, 90% had good
      mid-term results. Based on our experience and recent reports, balloon angioplasty
      is safe and effective in most children older than 7 months and should be
      considered a viable alternative to operation for discrete aortic coarctation.
      Further long-term evaluation is needed.

PMID- 10914256
TI  - [Recording nocturnal erections following injuries and insurance claims: cost
      effectiveness].
AB  - Road accidents, work accidents, or other trauma can cause impotence and are
      frequently followed by insurance claims. During 1990-97 we examined 230 males
      with such a complaint. All underwent full polysomnographic recordings in the
      sleep laboratory for 2 nights, during the course of which NPT (nocturnal penile
      tumescence) was examined with special equipment. It was assessed by an
      experienced technician following planned awakenings from REM sleep. In 75 of the
      230 subjects (33%), satisfactory erections were observed. In 100 (43%), who
      experienced at least 3 periods of REM sleep, no erections occurred. These
      patients were categorized as suffering from organic impotence. In the remaining
      55 (24%), the results were inconclusive, with only partial erections or not
      enough REM sleep periods. Since a man recognized as suffering from impotence may
      be awarded large monthly payments for life, these examinations, in our opinion,
      are an important tool to prevent unjustified claims, and can save the state
      unnecessary expenses.

PMID- 10914257
TI  - [Circadian fluctuations in the success and efficacy of streptokinase thrombolytic
      therapy in acute myocardial infarction].
AB  - This study was designed to assess possible diurnal fluctuations in the efficacy
      of thrombolysis with streptokinase. 156 consecutive patients treated with
      streptokinase during the period 1.1.95-1.7.96 were studied retrospectively.
      Success or failure of thrombolysis was determined according to the accepted
      clinical and angiographic criteria starting at midnight, 12 times at 2-hour
      intervals, then 8 times at 3-hour intervals, and then 6 times at 4-hour
      intervals. A definite peak for successful thrombolysis was found in the late
      afternoon and early evening hours. Between 16:00-20:00 PM, in 30.23% successful
      thrombolysis were observed, compared to 6.98% between 20:00-24:00 PM (p < 0.05)
      and in 10.53% between 00.00-04:00 AM (p < 0.05). Multiple regression analysis
      showed that the independent factor with the greatest impact on successful
      reperfusion was the actual time until thrombolysis (p = 0.037); then came the
      interval from pain onset to streptokinase administration (p = 0.020), while age
      and gender had much lesser impacts (p = 0.328 and 0.215, respectively), and
      individual risk factors even less. These findings may have several clinical
      implications: dose adjustment for the time of day may be required, with larger
      doses needed during morning hours, or preference for primary coronary angioplasty
      to avoid increase in bleeding complications due to higher doses of thrombolytic
      agents.

PMID- 10914258
TI  - [Knowledge and practice of primary care physicians relating to the treatment of
      streptococcal pharyngitis].
AB  - Knowledge and practice of primary care physicians as to diagnosis and treatment
      of group A, b-hemolytic streptococcal pharyngitis, and the degree to which they
      agreed with the medical literature and current clinical guidelines were examined.
      The study was conducted in a group of 195 general physicians, pediatricians, and
      family medicine specialists and residents. The data were collected using
      questionnaires which included personal information and questions relating to b
      hemolytic streptococcal pharyngitis and were analyzed by chi-square and t-tests,
      and logistic regression, as appropriate. A new dependent variable, good clinical
      practice (GCP), was defined as the total number of correct answers to the
      questions in the questionnaire. 147 of the 195 eligible physicians returned
      completed questionnaires, a compliance rate of 76%. 96.6% cited penicillin V as
      the drug of choice at a daily dosage of 1 g (43.7%) or 2 g (25.4%), for 10 days
      (90%). 133 physicians (90%) stated that the goal of penicillin therapy for b
      hemolytic streptococcal pharyngitis is to prevent late complications. 116
      physicians (82%) cited rheumatic fever as a complication of group A b-hemolytic
      streptococcal pharyngitis, preventable by appropriate antibiotic therapy.
      However, only 84 (59%) cited glomerulonephritis as a preventable complication.
      When the knowledge and attitudes of the respondents was analyzed in terms of the
      new variable, GCP, a significant association (p < 0.001) was found between
      physicians' attitudes and variables such as where they had studied medicine, and
      work seniority. Those with less seniority and or medical graduates of the
      Americas demonstrated greater knowledge and better clinical judgment than their
      more senior colleagues and graduates of European and Asian medical schools. Most
      primary care physicians in northern Israel treat group A b-hemolytic
      streptococcal pharyngitis as recommended in the medical literature. The level of
      medical studies in Israel and the Americas and the quality of training of
      residents in family medicine and pediatrics, have a positive influence on the
      degree of knowledge of as common a subject as b-hemolytic streptococcal
      pharyngitis. Emphasis should be placed on continuing medical education among
      primary care physicians, particularly veteran general physicians and those who
      studied in European or Asian medical schools.

PMID- 10914259
TI  - [How valid is the official data from the Health Department on reported morbidity
      in Israel? Hepatitis A as an example].
AB  - Hepatitis A is one of the most frequently reported notifiable infectious diseases
      in Israel. The annual incidence as reported is around 70/100,000. The physician
      or the diagnostic laboratory notifies the district health office of the Ministry
      of Health. The purpose of this research was to evaluate the sensitivity of
      passive surveillance of hepatitis A morbidity among adults, 18 years and over.
      Methods included study of notifications to the Ministry of Health or
      hospitalizations of cases of hepatitis A and of positive laboratory tests results
      (IgM) for hepatitis A. We estimated the extent of under-reporting by 2 different
      methods of extrapolation. Data based on passive surveillance among the adult
      population, between 1.1.1993-31.12.1994, comprised less than 1/5 of the actual
      number of cases. Physicians notified about 6.2% of their hepatitis A patients.
      5.1% of the notifications to the district health office were sent twice or more,
      usually both by the physicians and labs. The official data on hepatitis A
      morbidity, based on passive surveillance, are considerably underestimated.
      Physicians and public health officials should be aware that such data may not
      accurately reflect the magnitude of the risk or the amount of disease that can be
      prevented. Efforts should be made to improve this situation.

PMID- 10914260
TI  - [Atrioventricular junctional arrhythmia due to oral phenytoin intoxication].
AB  - Phenytoin (Dilantin) is the drug of choice for most of the convulsive disorders.
      However, even when given orally it causes many adverse reactions, mainly
      affecting the nervous system, both central and peripheral. When administered
      intravenously, severe cardiovascular reactions may occur, including conduction
      disorders, sinus arrest, atrioventricular block or hypotension. Medline screening
      did not reveal previous reports of arrhythmias induced by oral phenytoin. We
      present a case in which oral phenytoin administered chronically for a convulsive
      disorder caused atrioventricular junctional arrhythmia.

PMID- 10914262
TI  - [Fluid management in hemorrhagic shock--time for a change].

PMID- 10914261
TI  - [Reactive increase in blood pressure on immobilization, but not hypertension,
      prevents pressure ulcers].
AB  - Of 135 geriatric patients immobilized for at least 2 days, 37 (27.4%) had
      pressure ulcers (PU). Those without PU were the control comparison group. Gender,
      length of immobilization, number of blood pressure determinations and proportion
      with hypertension were similar in those with and without PU. Those with PU were
      slightly older than those in the comparison group: 75.5 +/- 8.8 and 74.7 +/- 9.6
      years, respectively (p > 0.05). Of 66 patients with acute ischemic stroke,
      reactive increase of systolic or diastolic blood pressure to 140/90 mm Hg or
      above following immobilization, was seen in 60.6% and 22.7% of patients,
      respectively, and there were PU in 12.1%. Of 17 with recurrent ischemic stroke,
      corresponding figures were: 41.2%, 23.5% (p > 0.05), and 47.1% (p < 0.01). In 7
      patients with previous ischemic stroke corresponding figures were: 14.3% and 0%
      (p < 0.01) and 100% (p < 0.001). In 36 operated for fracture of the femur,
      corresponding figures were: 50%, 11.1% (p > 0.05), and 27.8% (p > 0.05). For 9
      patients with severe infections, sepsis or pneumonia, the corresponding figures
      were: 22.2% and 0.0% (p > 0.05), and 44.4% (p < 0.04). The proportion of patients
      with reactive increase in systolic blood pressure on immobilization was lower in
      the PU group than in the controls, 27% vs 59.2%, (p < 0.001). The corresponding
      figures for reactive increase in diastolic blood pressure were similar, 8.1% and
      20.4%, respectively (p > 0.05). The mean systolic blood pressure on
      immobilization was higher in the control than in the PU group, 145.4 +/- 21.7 and
      130.8 +/- 14.9 mm Hg, respectively (p < 0.001). The corresponding figures for the
      mean diastolic blood pressure were similar, 81.2 +/- 10.5 and 75.7 +/- 8.9 mm Hg,
      respectively (p < 0.01). An increase in systolic blood pressure on immobilization
      reduced the risk of developing PU (p < 0.05). There was no significant
      statistical relation between diagnosis of hypertension and proportion of patients
      with PU (p > 0.05). Of 67 patients with hypertension, in 23.9% and 74.6% of them
      there was no increase in systolic or diastolic blood pressure, respectively.
      Statistical difference between lack of diastolic or systolic response was very
      significant (p < 0.001). Reactive increase of blood pressure, but not
      hypertension, predicts reduced risk of PU on immobilization in the hospitalized
      elderly. Diminished reactive increase of blood pressure in response to stress of
      any kind may be a criterion of frailty and reduced physiological reserves.
      Efforts to reduce elevated blood pressure when a patient is immobilized appear
      irrational.

PMID- 10914263
TI  - [Smoking and male impotence].

PMID- 10914264
TI  - [Use of transcutaneous electrical nerve stimulation in obstetrics and
      gynecology].

PMID- 10914265
TI  - [Ionizing irradiation for the prevention of coronary and peripheral artery
      restenosis].

PMID- 10914266
TI  - [Current approach for the evaluation and treatment of nodular thyroid disease].

PMID- 10914267
TI  - [Breast cancer prevention in high risk individuals: the surgical aspects].

PMID- 10914268
TI  - [Pregnancy and eyes--effect of pregnancy on the healty eye. I].

PMID- 10914269
TI  - [Osteoporosis in menopause: prevention and management].

PMID- 10914270
TI  - [Corticosteroid-induced osteoporosis-- prevention and treatment].

PMID- 10914271
TI  - [Reconstructive alternatives following segmental mandibulectomy].

PMID- 10914272
TI  - [Prehospital treatment of hemorrhagic shock].

PMID- 10914273
TI  - [Podiatric screening and assessment of the diabetic foot].

PMID- 10914274
TI  - [Ergogenic and clinical significance of creatine].

PMID- 10914275
TI  - [Penicillin allergy: an update. Part I: The significance of the diagnosis of
      penicillin allergy].

PMID- 10914276
TI  - Apparatus for making surgical motion pictures. 1932.

PMID- 10914278
TI  - How to prevent Denlinphobia. 1943.

PMID- 10914277
TI  - Photographing the plantar surface of the feet with weight bearing. 1942.

PMID- 10914279
TI  - Transilluminated color backgrounds in medical photography. 1944.

PMID- 10914280
TI  - Photomacrography of insects. 1954.

PMID- 10914281
TI  - Fluorescein angiography of the brain--the photographic procedure. 1978.

PMID- 10914282
TI  - A primer on digital imaging--post production for still photography: Part I. 1991.

PMID- 10914283
TI  - Uses of photography in the university. 1957.

PMID- 10914284
TI  - Reflection control in small object photography. 1966.

PMID- 10914285
TI  - Keynote address--BIO'76. 1977.

PMID- 10914286
TI  - Photomicrography: a translation into the vernacular: Part I--The illuminating
      system. 1987.

PMID- 10914287
TI  - A generation of editors give their thoughts on the editorial process. 1985.

PMID- 10914288
TI  - Reliability and validity of screening instruments for drug and alcohol abuse in
      adults seeking evaluation for attention-deficit/hyperactivity disorder.
AB  - A growing number of adults are seeking evaluation for Attention
      Deficit/Hyperactivity Disorder (ADHD). Screening for substance use disorders
      should be included as part of any comprehensive ADHD evaluation. We describe the
      validity and reliability of the Drug Abuse Screening Test (DAST) and the Alcohol
      Use Disorders Identification Test (AUDIT) in adults seeking evaluation for ADHD.
      Internal reliability estimates were excellent for both instruments. Scores on the
      DAST and AUDIT were higher among patients with a DSM-IV diagnosis of current drug
      abuse or dependence or current alcohol abuse or dependence, respectively. A
      cutoff score of 6 or above appears to be optimal for identifying individuals who
      are current drug abusers. A cutoff score of 6 or above on the AUDIT is suggested
      for detection of current alcohol abuse in this population. Comparable rates of
      substance use disorders were observed in ADHD and non-ADHD patients. Both
      measures are valid and reliable instruments for screening for alcohol and drug
      abuse among adults seeking evaluation for ADHD.

PMID- 10914289
TI  - The RAFFT as a screening tool for adolescent substance use disorders.
AB  - The objective of this study was to measure the sensitivity and specificity of the
      RAFFT, a screening instrument for problematic adolescent substance use. Two
      hundred and twenty-six adolescent patients, aged 13 to 18, who were referred to
      an emergency room or an ambulatory evaluation clinic were included. Patients
      answered the five questions of the RAFFT before a comprehensive psychiatric
      assessment was completed. Diagnoses were made according to DSM-IV. The best
      results were obtained with two positive answers on the RAFFT: a sensitivity of
      89% and a specificity of 69% in the screening for substance abuse or dependence.
      The RAFFT performed well in this highly selected patient population.

PMID- 10914290
TI  - Age of onset as a discriminator between alcoholic subtypes in a treatment-seeking
      outpatient population.
AB  - Subtyping alcoholics may provide a more accurate guide as to the course and
      character of the disease. Classifications of different ages of onset of problem
      drinking have so far resulted in categorical inconsistencies. In the past,
      hospital-based alcoholics have over-represented those most severely ill, and
      comprehensive evaluations of psychopathology for discriminating between alcoholic
      subtypes have been infrequent. In a heterogeneous treatment-seeking, outpatient,
      alcoholic population, we tested the hypothesis that age of onset represents a
      continuum of disease, and that greater severity of psychopathology is associated
      with lower ages of onset. Using a standard questionnaire, 253 male and female
      treatment-seeking alcoholics were stratified according to specific ages of onset:
      a) < 20 years; b) 20-25 years, and c) > 25 years. These age of onset groups were
      compared on alcohol severity and craving, family history, childhood behavior,
      personality, hostility, overt aggression, mood, and social functioning. Symptom
      severity and age of onset were negatively correlated, and the 20-25-year onset
      group usually had intermediate scores. The < 20 year onset group was
      characterized by greater severity of alcohol-related problems, family history,
      childhood behavioral problems, craving, hostility, antisocial traits, mood
      disturbance, and poor social functioning. Alcoholics with an earlier age of onset
      have relatively greater psychopathology than those of later onset. While the
      preponderance of psychopathology among those in the < 20-year onset group could
      be conceptualized as a clinical "subtype," such a characterization would not
      define an entirely homogeneous category. Yet, this clinical characterization
      would be clinically important if specific age of onset levels were found to be
      differentially sensitive to pharmacological and/or psychological treatments.

PMID- 10914291
TI  - Stimulant psychosis: symptom profile and acute clinical course.
AB  - Nineteen patients seen at a psychiatric emergency service with amphetamine- or
      cocaine-induced psychotic disorder were assessed with structured interviews,
      chart review, and blood and urine testing. All had a predominance of positive
      symptoms from the Positive and Negative Syndrome Scale (PANSS). However, some
      subjects had substantial Negative Scale scores (26%), bizarre delusions (95%),
      and Schneiderian hallucinations (63%), mimicking a broad range of schizophrenic
      symptoms. Several PANSS scores were correlated with treatment intensity: Positive
      score with seclusion hours, General Psychopathology and Negative scores with
      hospitalization length, and General Psychopathology score with neuroleptic dose.
      Presenting symptoms may help in treatment planning.

PMID- 10914292
TI  - Importance of identifying cocaine and alcohol dependent methadone clients.
AB  - Clients in outpatient methadone treatment (OMT) who abuse cocaine or alcohol are
      difficult to engage and retain in treatment. The impact a triple addiction to
      these drugs has on treatment was the focus of this study (N = 127). Admission
      characteristics, treatment response, and retention were compared among clients
      dependent on opiates only (O), opiates and alcohol (OA), opiates and cocaine
      (OC), or all three drugs (OAC). Findings indicate these groups differ in
      admission needs assessment, session attendance, issues discussed during
      treatment, and development of counselor rapport, with the OAC group being
      significantly more difficult to engage and retain in treatment.

PMID- 10914293
TI  - Cocaine dependence with and without post-traumatic stress disorder: a comparison
      of substance use, trauma history and psychiatric comorbidity.
AB  - This study examined the relationship between substance use, trauma history, post
      traumatic stress disorder (PTSD), and psychiatric comorbidity in a treatment
      seeking sample of cocaine dependent individuals (N = 91). Structured clinical
      interviews revealed that 42.9% of the sample met DSM-III-R criteria for lifetime
      PTSD. Comparisons between individuals with and without lifetime PTSD revealed
      that individuals with PTSD had significantly higher rates of exposure to
      traumatic events, earlier age of first assault, more severe symptomatology, and
      higher rates of Axis I and Axis II diagnoses. The results illustrate a high
      incidence of PTSD among cocaine dependent individuals. Routine assessment of
      trauma history and PTSD may assist in the identification of a subgroup of cocaine
      users in need of special prevention and treatment efforts.

PMID- 10914294
TI  - The effect of sertraline on methadone plasma levels in methadone-maintenance
      patients.
AB  - The authors examine methadone plasma levels in 31 depressed methadone-maintained
      opiate addicts enrolled in a 12-week placebo-controlled, double-blind study of
      sertraline. Between baseline and week 6, patients on sertraline showed a mean
      increase in methadone plasma level/dose (P/D) ratio of 26% (SD = 43%, range -32%
      to +118%), while patients on placebo showed a mean decrease of 16% (SD = 27%,
      range -62% to +50%). This difference was significant (p < 0.02). The sertraline
      and placebo groups did not differ in reported side effects or methadone dose
      adjustments. Between weeks 6 and 12, methadone P/D in the sertraline group
      decreased back towards baseline, and the treatment groups did not differ
      significantly at week 12. The results suggest sertraline may produce a modest
      increase in methadone serum levels over the first six weeks of treatment.
      Depression and anxiety disorders are common in methadone-maintained patients.
      Serotonin uptake inhibitors are attractive choices for treatment due to their low
      toxicity and low abuse potential, but these agents variously inhibit isoenzymes
      responsible for the metabolism of methadone. Clinicians treating depressed or
      anxious methadone patients with second-generation antidepressants should monitor
      for clinical signs of increased or decreased methadone levels and consider
      monitoring serum methadone levels.

PMID- 10914295
TI  - The impact of amphetamine-related disorders on community psychiatric emergency
      services: 1993-1997.
AB  - Trends in number, relative prevalence, and demographics of adult psychiatric
      admissions to the county psychiatric emergency service in Sacramento, California,
      for treatment of Amphetamine-Related Disorders (ARDs) (N = 2,428) between July
      1993 and July 1997 were examined. ARDs accounted for 11.2% of all emergency
      admissions (N = 21,615) and were the most frequent substance-related disorder
      requiring admission during the study period. Patients with ARDs tended to be
      Caucasian or Hispanic males in their mid 30s. 38% of the ARD patients required
      further inpatient psychiatric care. The trends in numbers of ARDs tended to
      parallel other local and national non-psychiatric indicators of amphetamine
      induced morbidity.

PMID- 10914296
TI  - Addiction, community and state: a review.
AB  - As clinicians, we are well aware of the importance of drug supply, price,
      availability, and access in propagating and maintaining illicit drug use, abuse,
      and addiction. However, we tend to be silent on these topics, leaving them to
      elected and appointed government leaders. The author proposes that our remaining
      silent is analogous to an infectious disease expert remaining silent on water
      supply and sewage in the midst of a cholera epidemic. It is not only unseemly for
      us to remain silent, it is unprofessional at best and unethical at worst.
      Governmental means of addressing the social genesis of addiction and illicit drug
      supply falls under the general rubric of statecraft. Our elected leaders, our
      appointed governmental leaders, and our publicly supported workers (e.g., police,
      courts, schools, health care workers, social agencies) can and do exert
      influences either favoring or counteracting illicit drug supply, use, abuse, and
      addiction. Public officials can and do learn the exercise of statecraft in
      addressing a large range of social needs, such as housing, transportation,
      security, a safe food supply, and so forth. They can and should develop
      knowledge, skills, and experience in the exercise of statecraft vis-a-vis drugs.
      This article reviews the relevant literature on this topic. In addition, the
      author reflects on his observations on "addiction statecraft" in several
      countries over the past three decades. He underscores the need to consider
      elements such as community deterioration, corruption of police and other
      officials, and social anti-drug strategies that have worked as well as those that
      have not worked. Public leaders must also take stands regarding intervention and
      treatment programs that are not widely popular, such as those involving
      methadone. The author argues that we speak out authoritatively on "addiction
      statecraft." In undertaking such social roles, we must take care to speak out of
      our own collective wisdom and experience, rather than out of personal bias or
      personal agendas.

PMID- 10914297
TI  - Motivational interviewing with psychiatrically ill substance abusing patients.
AB  - This pilot study reports the relative efficacy of a one-session preadmission
      motivational interview (n = 13) compared to a standard preadmission interview (n
      = 10) for psychiatrically ill substance abusing patients in a partial hospital
      program.

PMID- 10914298
TI  - Detoxification with buprenorphine of a pregnant heroin addict.
AB  - This is a case report and literature review concerning the use of buprenorphine
      for detoxification in a pregnant addict. It presents the clinical management of
      the complexities of opiate addiction and pregnancy. I suggest a more vigorous
      study of buprenorphine for opiate withdrawal in motivated pregnant addicts.

PMID- 10914299
TI  - Alcohol withdrawal in an 11-year-old.

PMID- 10914300
TI  - Zolpidem dependence and prescription fraud.

PMID- 10914301
TI  - Secondary nocturnal enuresis.
AB  - Secondary nocturnal enuresis accounts for about one quarter of patients with bed
      wetting. Although a psychological cause is responsible in some children, various
      other causes are possible and should be considered. This article reviews the
      epidemiology, psychological and social impact, causes, investigation, management,
      and prognosis of secondary nocturnal enuresis.

PMID- 10914302
TI  - Clinical factors associated with focal infiltrates in wheezing infants and
      toddlers.
AB  - It can be challenging to determine which findings are associated with focal
      infiltrates in young wheezing children. A prospective study of wheezing children
      < or = 18 months of age revealed focal infiltrates on chest radiograph in 23%. By
      use of multivariate analysis, findings significantly associated with focal
      infiltrates included grunting (OR 4.1, 95% CI, 2.0, 8.6) and oxygen saturation <
      or = 93% (OR 2.2, 95% CI, 1.1, 4.8); with a sensitivity and specificity of 12.5%
      and 97%, respectively. Variables not associated with focal infiltrates included
      first-time wheezing, fever, and tachypnea. The combination of grunting and oxygen
      saturation < or = 93% is highly specific and can be used to help diagnose
      pneumonia in wheezing infants and toddlers.

PMID- 10914303
TI  - Infant colic syndrome--maternal fantasies of aggression and infanticide.
AB  - This study examined the impact of infant colic on the emotional state of the
      mother. Subjects were 23 pairs of mothers and their colicky infants. Structured
      interviews were conducted with mothers to elicit details around the colic episode
      and included (1) the emotional state experienced by the mother, (2) the quality
      and content of the mother's fantasies in response to her infant, and (3) the
      emotional impact on the parents. Explicit aggressive thoughts and fantasies were
      revealed by 16 (70%) of the mothers while six (26%) admitted thoughts of
      infanticide during their infant's colic episodes, a finding notable because
      previously this has not been documented in medical literature. All mothers
      experienced physical and psychological symptoms in response to their infant's
      colic. More than 90% of the mothers with a colicky infant experienced significant
      marital tension and disruption in their social contacts. The findings suggest
      that physician receptivity and skill in uncovering the physical and psychological
      impact of colic on parents is essential for the physical and emotional well-being
      of the family. Active support and counseling by physicians is critical to
      diminish any potential for abuse and infanticide in these infants.

PMID- 10914304
TI  - The challenge of colic.

PMID- 10914305
TI  - Prevalence of SIDS risk factors: before and after the "Back to Sleep" campaign in
      North Dakota Caucasian and American Indian infants.
AB  - The objective of this study was to compare rates of infant sleeping position and
      other risk factors for sudden infant death syndrome from 1991 before the "Back to
      Sleep" campaign to rates in 1998 after the campaign. We used a cross-sectional
      risk factor prevalence study of risk factors for the years 1991 and 1998. In
      North Dakota the prevalence rates of prone sleeping declined 72% for American
      Indian infants and 62% for Caucasian infants. We were unable to identify a
      corresponding decline in SIDS in North Dakota for this time period. The
      relationship between sleeping position and SIDS may be more complex in rural and
      frontier settings and in American Indian populations than in urban and majority
      populations. The generalizability of this study is limited by the rural setting
      and small sample size. Longer term surveillance and additional reports from sites
      with pre "Back to Sleep" data as a baseline for both SIDS rates and sleeping
      position will be important to clarify the rate of prone sleeping position and
      SIDS.

PMID- 10914306
TI  - A 5-year-old female with hypertensive crisis.

PMID- 10914307
TI  - Hypertension with lower extremity traumatic amputation.

PMID- 10914308
TI  - Urine output in infants with respiratory distress syndrome treated with
      surfactant.

PMID- 10914309
TI  - Racial differences in the lipid profiles of obese children and adolescents before
      and after significant weight loss.

PMID- 10914310
TI  - Of mind, body, and modern technology.

PMID- 10914311
TI  - Necrobiosis lipodica diabeticorum.

PMID- 10914312
TI  - False aneurysm of the external carotid artery.

PMID- 10914313
TI  - An overview of computer-integrated surgery and therapy.
AB  - Computer-integrated surgery and therapy (CIST): Methods and systems to help the
      surgeon or the physician use multimodality data (mainly medical images) in a
      rational and quantitative way, in order to plan but also to perform medical
      interventions through the use of passive, semi-active, or active guiding systems.

PMID- 10914314
TI  - Fetal ultrasound.
AB  - Ultrasound provides an opportunity to visualize the fetus and to assess its
      response to the intrauterine environment. The topic of fetal ultrasound is broad,
      and whole textbooks have been devoted to areas such as the diagnosis of
      anomalies. In an effort to provide current practical information, I have focused
      on the most common clinical questions asked when pregnant women are referred for
      obstetric ultrasound. We review the diagnoses of oligohydramnios, polyhydramnios,
      intrauterine growth retardation (IUGR), macrosomia, multiple pregnancy, and
      common fetal anomalies. Noninvasive assessment of fetal well-being is addressed,
      along with the use of sonography to refine risk assessment in patients with
      abnormal antenatal screening tests.

PMID- 10914315
TI  - Potential applications of carbomer in oral mucoadhesive controlled drug delivery
      system: a review.
AB  - Carbomers are extensively being used in controlled drug delivery systems (CDDS).
      They are also finding numerous applications in oral mucoadhesive drug delivery
      because of their ability to interact with the mucus glycoprotein and to remain
      localized to a specific site. The present review aims at giving an insight into
      the potential application of carbomers in mucoadhesive CDDS. This review deals
      with the physicochemical properties of carbomers and various mechanisms of
      mucoadhesion. The mechanism for the release of the drug, both water soluble and
      water insoluble, is discussed. The use of carbomers in oral delivery of peptides
      or protein-based drugs is also covered.

PMID- 10914316
TI  - Characterization and evaluation of tenoxicam coprecipitates.
AB  - Tenoxicam is a nonsteroidal anti-inflammatory drug belonging to the oxicam group.
      The drug is slightly soluble in water. In a trial to increase its dissolution,
      different commonly used excipients were selected to prepare coprecipitates with
      tenoxicam. The coprecipitates were prepared using the solvent evaporation method,
      and the ratio used was 1:3 drug to additive. The prepared coprecipitates were
      subjected to a dissolution study, and they were characterized using infrared (IR)
      and differential scanning calorimetry (DSC) techniques. Dissolution profiles of
      most of the prepared coprecipitates demonstrated higher dissolution than pure
      tenoxicam. The characteristic peaks of tenoxicam in the IR spectrum disappeared
      in the spectra of all the prepared coprecipitates except those prepared with
      sodium chloride, for which the IR spectrum was identical to that of the pure
      drug. The characteristic peaks of tenoxicam disappeared in the DSC thermograms of
      the coprecipitates under study, indicating a change in structure from pure
      tenoxicam. Characterization of the coprecipitates by IR and DSC techniques
      revealed structural changes in the prepared coprecipitates from the plain drug,
      which may account for increased dissolution rates.

PMID- 10914317
TI  - Properties of hot-melt extruded theophylline tablets containing poly(vinyl
      acetate).
AB  - The objectives of this study were to investigate the properties of poly(vinyl
      acetate) (PVAc) as a retardant polymer and to study the drug release mechanism of
      theophylline from matrix tablets prepared by hot-melt extrusion. A physical
      mixture of drug, polymer, and drug release modifiers was fed into the equipment
      and heated inside the barrel of the extruder. The cylindrical extrudates were
      either cut into tablets or ground into granules and compressed with other
      excipients into tablets. Due to the low glass transition temperature of the PVAc,
      the melt extrusion process was conducted at approximately 70 degrees C.
      Theophylline was used as the model drug in this study. Theophylline was present
      in the extrudate in its crystalline form and was released from the tablets by
      diffusion. The Higuchi diffusion model and percolation theories were applied to
      the dissolution data to explain the drug release properties of the matrix
      systems. The release rate was shown to be dependent on the granule size, drug
      particle size, and drug loading in the tablets. Water-soluble polymers were
      demonstrated to be efficient release rate modifiers for this system.

PMID- 10914318
TI  - The theoretical basis for scaling-up by the use of the method of microwave
      granulation.
AB  - For the scaling-up achieved by the use of the method of wet microwave granulation
      based on calculations, there is a need for an exact mathematical description for
      the relationship between the dose of radiation and the resultant effect. By
      assessing the physical, physical-chemical, and chemical factors, we may conclude
      that, by the gross kinetic evaluation of the change in the enthalpy and the loss
      of humidity, there is a possible solution for the mathematical description of the
      single-step, single-pot granulation from the practical aspect of finding ways to
      scale-up. This paper overviews the experiments performed in a laboratory-size
      microwave vacuum granulator in testing two different granules with respect to
      composition and permittivity and presents the evaluation of the experimental
      data.

PMID- 10914319
TI  - Role of base plate rotational speed in controlling spheroid size distribution and
      minimizing oversize particle formation during spheroid production by rotary
      processing.
AB  - The occurrence of material adhesion and formation of oversize particles in the
      product yield during one-pot spheroid production by rotary processing leads to a
      less predictable process and a decrease in the usable portion of the total
      product yield obtained from each production run. The use of variable speeds of
      the rotating frictional base plate during the spheronization run was investigated
      for achieving optimal spheroid production. When the base plate speed was
      increased during liquid addition, the greater centrifugal forces generated
      improved liquid distribution and the mixing of the moist powder mass, resulting
      in a decrease in the amount of oversize particles formed. When the base plate was
      maintained at a high speed throughout the run, the amount of oversize particles
      and mean spheroid size increased, and a greater "between batch" mean spheroid
      size variability was also observed. The findings showed that, when higher speeds
      were used, the residence time must be adjusted accordingly to avoid excessive
      coalescence and growth while maintaining even liquid distribution. A "low-high
      low" speed variation during rotary processing may be used to produce spheroids
      with a narrow size distribution and with a minimal amount of oversize particles
      in the total product yield.

PMID- 10914320
TI  - Captopril floating and/or bioadhesive tablets: design and release kinetics.
AB  - Two viscosity grades of hydroxypropylmethylcellulose (HPMC 4000 and 15,000 cps)
      and Carbopol 934P were used to prepare captopril floating tablets. In vitro
      dissolution was carried out in simulated gastric fluid (enzyme free) at 37
      degrees C +/- 0.1 degree C using the USP apparatus 2 basket method. Compared to
      conventional tablets, release of captopril from these floating tablets was
      apparently prolonged; as a result, a 24-hr controlled-release dosage form for
      captopril was achieved. Drug release best fit both the Higuchi model and the
      Korsmeyer and Peppas equation, followed by first-order kinetics. While tablet
      hardness and stirring rate had no or little effect on the release kinetics,
      tablets hardness was found to be a determining factor with regard to the buoyancy
      of the tablets.

PMID- 10914321
TI  - Prediction of drug solubility in ternary solvent mixture.
AB  - Applicability of the combined, nearly ideal, binary solvent/Redlich-Kister
      equation for calculating drug solubility in ternary mixtures is presented. The
      advantages of the proposed model are discussed and compared with a recently
      published equation that calculates the solute solubility in ternary solvent
      mixtures based on the mixture response methodology.

PMID- 10914322
TI  - Rheological behavior of nasal sprays in shear and extension.
AB  - The rheological profiles of commercial corticosteroid nasal spray suspensions
      (Beconase, Nasacort, Flixonase, and Nasonex) were compared using shear and
      extensional techniques. Thixotropy/shear thinning was investigated (Carri-Med
      CSL100, concentric cylinder geometry) by (a) the generation of flow curves at low
      (100 sec-1) and high (1200 sec-1) maximum shear rates and (b) determination of
      equilibrium shear viscosities at constant shear rates of 10 sec-1, 100 sec-1, or
      1200 sec-1. Extensional properties, on which droplet breakup and size depend,
      were examined using digital camera photography of droplet evolution and the
      length any trailing filament formed when the suspension was extruded from a 10-ml
      syringe at 500 microliters/min. All the nasal suspensions were shear thinning and
      were also thixotropic to varying degrees. The absence of significant thixotropic
      recovery at short times (5 min) for all the sprays implies that thixotropy is not
      necessarily the controlling factor for prolonged residence of the spray in the
      nasal cavity, but rather that it is the high viscosities present in all four
      sprays, even after structure breakdown. Preliminary extensional flow data
      identified differences among the four sprays, with extensional filament lengths
      increasing in the same rank order as the lowest shear rate (10 sec-1) equilibrium
      viscosities.

PMID- 10914323
TI  - Accelerated fluid bed drying using NIR monitoring and phenomenological modeling.
AB  - A "fast-drying" method to accelerate the fluid bed drying process is presented.
      It relies on concepts of heat and mass transfer with real-time near-infrared
      (NIR) monitoring of moisture. Triplicate trials show that fast drying can reduce
      granulation drying time by half over single-temperature cycles. The product is
      equivalent in every way tested to material made using a conventional cycle even
      though the inlet temperature throughout the constant-rate stage was higher than
      the melting point of the compound. Tablets made from the fast-dried granulation
      exhibit equivalent physical characteristics to tablets made from granulations
      dried at a single, lower temperature.

PMID- 10914325
TI  - Stability study of hard gelatin capsules containing retinoic acid.
AB  - Retinoic acid (RA) is employed in the therapeutic treatment of acute
      promyelocytic leukemia (APL). In this paper, the chemical stability and the most
      favorable storage conditions of RA in hard gelatin capsules containing alpha
      lactose monohydrate, used in clinical experimentation, are reported. A secondary
      goal of this work was to show the usefulness of a robust regression technique,
      repeated median with replicates (RMWR) in a solid-state shelf life prediction by
      accelerated studies. The capsules were stored at room temperature and in the
      freezer. Their residual RA content was assayed for more than 3 years. RA chemical
      degradation was monitored by high-performance liquid chromatography (HPLC) and
      thin-layer chromatography (TLC) stability-indicating methods previously validated
      and able to detect various potential degradation products. Possible physical
      modifications were checked by dissolution tests and differential scanning
      calorimetry (DSC) of the content of the capsules. The shelf life was also
      predicted by an accelerated isothermal method to confirm room temperature
      results, and the activation energy estimated through this study was 12.5 +/- 1.1
      kcal/mol (95% confidence interval). In the conditions of climatic zone II, the
      shelf life for the capsules stored at room temperature in light-resistant
      containers was equal to 678 days, while the capsules stored in the freezer
      retained the initial content of drug after 1289 days. From the results gathered
      in this study, the usefulness of RMWR for shelf life prediction in the presence
      of outliers is evident.

PMID- 10914324
TI  - Enhancement of dissolution and bioavailability of piroxicam in solid dispersion
      systems.
AB  - Solid dispersion systems of water-insoluble piroxicam in polyethylene glycol
      (PEG) 4000 and in urea were prepared by fusion and solvent methods and were
      characterized in this study. The in vitro dissolution studies showed that the
      dispersion systems containing piroxicam and PEG4000 or urea gave faster
      dissolution than the corresponding simple mixtures. The differential scanning
      calorimetry (DSC) study indicated that the piroxicam-PEG system prepared by the
      fusion method is a solid dispersion, while the piroxicam-urea system prepared by
      the solvent method is likely to be a solid solution of piroxicam in urea. The
      storage testings showed that all dispersions were stable, except that uptake of
      water during storage may occur in the PEG system. A single-dose study with
      rabbits showed that the dispersion systems provided statistically significant to
      a higher extent and rate of bioavailability than the corresponding physical
      mixture (p < 0.05).

PMID- 10914326
TI  - Effect of hydroxypropyl-beta-cyclodextrin on the solubility of an antibacterial
      isoxazolyl-naphthoquinone.
AB  - The complexation of 2-hydroxy-N-(3,4-dimethyl-5-isoxazolyl)-1,4-naphthoquinone-4
      imine (I) with a highly soluble cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP
      beta-CD) was studied in aqueous media by solubility methods. I is an
      antibacterial and trypanocidal agent that is undergoing preclinical testing.
      Unfortunately, I exhibits low water solubility, and it is therefore difficult to
      prepare the solutions for biological tests. I inclusion took place with 1:1
      stoichiometry. The stability constants of the I complexes calculated from the
      slope and the intercept of the phase solubility diagrams are larger in the less
      ionized form, whereas greater overall solubility is obtained in basic media.

PMID- 10914327
TI  - Anaerobic stability of aqueous physostigmine solution.
AB  - The anaerobic stability of physostigmine was studied in this report.
      Physostigmine and two important degradants, eseroline and rubreserine, were
      identified by a high-performance liquid chromatography (HPLC) system using a
      photodiode array detector and a UV detector at the retention times of 12.4, 9.2,
      and 7.9 min. Under anaerobic treatment, the minimum degradation rate constant was
      found at pH 3.4, evaluating from pH-rate profiles at 45 degrees C, 55 degrees C,
      and 70 degrees C with the pH range 2.4-6.8. The degradation of physostigmine was
      suggested as specific acid-base catalysis. Anaerobic activation energies of KH,
      K(OH), and Kobs were 9.4, 8.3, and 17.9 kcal/mol, respectively. The ratios of
      observed aerobic and anaerobic rate constants were 2-33 at 88 degrees C, which
      had a trend to increase ratios as pH increased in the range 2.4-5.2. The shelf
      life of physostigmine solution was estimated to be 4 years at room temperature
      under anaerobic conditions at pH 3.4.

PMID- 10914328
TI  - Influence of Avicel PH-301 on the compressibility of alpha-methyldopa and
      phenobarbitone in direct compression.
AB  - The aim of this work was to investigate the compressibility behavior of alpha
      methyldopa and phenobarbitone using a Korsch EK0 instrumented eccentric tablet
      machine, with force-time and force-displacement curves constructed and applied to
      calculate different compressional values to study the compressional behavior. The
      results of this work revealed a difference in compressibility behavior between
      the two drugs during the compressional process. alpha-Methyldopa gave an abnormal
      compressional curve with high friction in the pre- and postcompressional phases.
      A residual force could be seen on the lower punch. Furthermore, capping and
      sticking were observed visually during tablet pressing, indicating poor
      compressibility behavior. In the case of phenobarbitone, no friction was observed
      in the precompressional phase, but there was higher friction in the
      postcompressional phase, especially in the ejection phase. The compressibility of
      the drugs was improved by the addition of Avicel PH-301 and magnesium stearate.

PMID- 10914329
TI  - The influence of plasticizer molecular weight on spreading droplet size of HPMC
      aqueous solutions using an indirect method.
AB  - Film coating is a complex process that involves many factors. To ensure spreading
      and/or film capability, plasticizers are added. The role of different molecular
      weights of polyethylene glycol on the behavior of hydroxypropylmethylcellulose
      (HPMC) with different grades was determined and compared with values for the film
      without the plasticizer using a real method for spreading. The droplet size,
      distribution, and shape were analyzed as the criterion. The results show that the
      polymer grades and plasticizer types are important in droplet size formation.

PMID- 10914330
TI  - Induction of AP-1 binding to intron 1 of SP-A1 and SP-A2 is implicated in the
      phorbol ester inhibition of human SP-A promoter activity.
AB  - A deletional analysis of the SP-A1 promoter in NCI-H441 cells was performed to
      identify potential cis-acting elements involved in phorbol ester-mediated
      repression of human SP-A transcription. The phorbol ester TPA reduced SP-A1 and
      SP-A2 promoter activity to approximately 35% to 45% compared to that of control
      cells. The inhibitory effect of TPA was significantly reduced upon removal of the
      region +64/+394 relative to the SP-A1 transcription start site. Using NCI-H441
      nuclear proteins, electromobility shift assay analysis showed that the intron
      region +309/+329 of SP-A1 and the corresponding region of SP-A2 formed sequence
      specific DNA/protein complexes that were induced by TPA exposure. The region
      +318/+324 of SP-A1 contains sequences similar to a consensus AP-1 binding site,
      TGACTGA (TCACTGA for SP-A2), which when mutated (TGAGAGT) prevented the formation
      of the TPA-induced DNA/protein complex. The TPA-induced complex was supershifted
      in the presence of antibody against the Jun family of proteins, but not the Fos
      family of proteins. These results suggest that the binding of AP-1 or an AP-1-
      like factor to the first intron of SP-A1 and SP-A2 may be involved in the phorbol
      ester inhibition of human SP-A gene expression.

PMID- 10914331
TI  - Phloretin inhibits Na+ and K+ uptake in cultured alveolar type II cells by
      reduction of cellular ATP content.
AB  - A number of Na+ and K+ transport pathways have been identified in the alveolar
      epithelium and multiple inhibitors have been used to uncover these mechanisms.
      However, the effect of phloretin, a small dipolar nonelectrolyte compound which
      exerts many effects on membrane transport on Na+ and K+ uptake in alveolar
      epithelial cells, is not known. The purpose of this study was then to determine
      the impact of phloretin in Na+ and K+ uptake in cultured rat alveolar type II
      cells. Phloretin at a dose of 250 microM decreased Na+ uptake by 80% and K+
      uptake by 90%. This decrease in Na+ and K+ uptake was not associated with a
      cytotoxic effect of phloretin, but this treatment did decrease ATP levels in the
      cells to 80% of the control cells value by 5 minutes and to 95% by 10 minutes.
      Our study demonstrates that phloretin is a nonspecific inhibitor of ions
      transport in alveolar type II cells. This inhibition is probably mediated by a
      reduction of intracellular ATP content.

PMID- 10914332
TI  - Effects of reactive oxygen species on intracellular calcium in bovine tracheal
      epithelium: modulation by nitric oxide.
AB  - We studied the effects of reactive oxygen species (ROS) on intracellular Ca2+
      concentration ([Ca2+]i) and their possible modulation by nitric oxide (NO) in
      fura-2-loaded cultured bovine tracheal epithelium. Hypoxanthine (HX) and xanthine
      oxidase (XO), which generate superoxide anion (O2-) and hydrogen peroxide (H2O2),
      dose dependently increased [Ca2+]i. The increase in [Ca2+]i was reduced in the
      presence of superoxide dismutase (SOD, 200 U/mL) and catalase (200 U/mL) by 29%
      and 43%, respectively. The iron chelator o-phenanthroline and the hydroxyl
      radical (.OH) scavenger dimethylthiourea (DMTU) more potently inhibited the
      response of [Ca2+]i. H2O2-derived .OH generated by the Fenton reaction caused a
      marked [Ca2+]i elevation, but exogenous H2O2 did not. Sodium nitroprusside (100
      microM), an NO donor, potentiated HX-XO-induced [Ca2+]i rise by 50%, an effect
      that was abolished in the presence of SOD or DMTU. These results suggest that .OH
      formed by interaction of O2- and H2O2 in the presence of iron may play a major
      role in the HX-XO-induced disruption of airway epithelial Ca2+ homeostasis, and
      that NO potentiates ROS-induced [Ca2+]i response, presumably by reacting with O2-
      and producing .OH.

PMID- 10914333
TI  - Effects of peroxynitrite on pulmonary edema and the oxidative state.
AB  - Excess nitric oxide (NO) generation in the presence of superoxide anion (O2-)
      leads to the formation of peroxynitrite which may result in lung injury. Oxidant
      mediated lung injury has a critical role in pulmonary diseases. We therefore
      determined whether peroxynitrite causes lung fluid accumulation, lipid
      peroxidation, and formation of nitrotyrosine using an isolated perfused rat lung
      model. The lung weight gain during bolus peroxynitrite infusion increased in a
      dose-dependent manner over a range of 3 to 30 mumole. Concomitantly,
      bronchoalveolar lavage Ficoll also increased, indicative of increased endothelial
      permeability. Peroxynitrite increased the production of thiobarbituric acid
      reactive substances, an index of lipid peroxidation. Furthermore, nitrotyrosine
      levels in lung tissue rose with increased concentration of peroxynitrite, as
      determined by Western blot using antinitrotyrosine antibodies. These results
      suggest that peroxynitrite, formed from NO and O2-, leads to increased pulmonary
      fluid accumulation, possibly through lipid peroxidation and/or nitration of cell
      membrane proteins.

PMID- 10914334
TI  - Characterization of the pulmonary N-ethylmaleimide-insensitive phosphatidate
      phosphohydrolase.
AB  - Phosphatidate phosphohydrolase (PAPase) is a key enzyme involved in glycerolipid
      synthesis where it converts phosphatidic acid to diacylglycerol. Previous studies
      performed in lung have demonstrated the existence of 2 different forms of
      PAPases, namely PAP-1 and PAP-2. The former pulmonary Mg+2-dependent enzyme is N
      ethylmaleimide (NEM)-sensitive, heat labile, and is involved in phospholipid
      biosynthesis. However, the function of the latter lung isozyme is unknown. PAP-2
      activity was selectively assayed using NEM in the absence of Mg+2. Studies
      employing this assay and adult rat lung microsomal preparations demonstrated that
      PAP-2 activity was inhibited by amphiphilic amines, sphingoid bases, products of
      the PAP-2 reaction (monoacylglycerol [MAG] and diacylglycerol [DAG]), and
      substrate analogs such as lysophosphatidic acid (lyso-PA), ceramide-1-phosphate,
      and to a lesser extent, sphingosine-1-phosphate. Purified lung plasma membranes,
      prepared using discontinuous sucrose and Percoll gradients, showed that PAP-2
      activity was enriched 6.9 +/- 1.6-fold over the whole homogenate and was between
      the enrichment for plasma membrane markers, 5'-nucleotidase (14.7 +/- 0.3) and
      Na+, K(+)-ATPase (4.0 +/- 0.2). Both phosphatidic acid and lysophosphatidic acid
      were good substrates for PAP-2 activity in this purified plasma membrane
      fraction. In contrast, sphingosine-1-phosphate was a relatively poor substrate.
      PAP-2 activity was slightly enriched in isolated type II cells and low in
      isolated rat lung fibroblasts. This study shows lung contains PAP-2 activity in
      plasma membranes and type II cells where it could play a role in signal
      transduction.

PMID- 10914336
TI  - Should color vision screening yield a black or white answer?

PMID- 10914335
TI  - Cell-specific expression of CCAAT/enhancer-binding protein delta (C/EBP delta) in
      epithelial lung cells.
AB  - CCAAT/enhancer-binding proteins (C/EBP) constitute a family of transcription
      factors that are involved in regulation of proliferation and differentiation in
      several cell types. In epithelial lung cells the C/EBP alpha isoform seems to
      play a role in the regulation of surfactant proteins (SP) and Clara cell specific
      protein (CCSP), whereas the roles of C/EBP beta and C/EBP delta are unclear. We
      have examined the protein levels of C/EBP delta in bronchiolar Clara cells and
      alveolar type 2 cells, and its relation to the expression of lung specific
      proteins and cell proliferation. The protein expression of C/EBP delta was high
      in freshly isolated Clara cells compared to type 2 cells. In both cell types
      C/EBP delta levels increased during culture. Alterations of the levels of C/EBP
      delta did not correspond with the proliferation levels of Clara cells, but seemed
      to correspond in type 2 cells. Clara cell secretory protein (CCSP) was highly
      expressed in freshly isolated Clara cells, in contrast to type 2 cells. SP-D and
      CYP2B1 were expressed at somewhat higher levels in Clara cells than in type 2
      cells, whereas SP-A exhibited highest expression in type 2 cells. During culture
      the levels of all these lung proteins were strongly reduced. However, compared to
      with serum we found an increase in CCSP in Clara cell cultures without serum, and
      this correlated with an increase in C/EBP delta. Overall our in vitro data
      suggest that C/EBP delta alone is not related to the maintenance of proteins
      involved in differentiation.

PMID- 10914337
TI  - Hazardous materials readiness of United States level 1 trauma centers.
AB  - Injuries caused by hazardous materials (hazmat) accidents are common in the
      United States, and emergency departments should be capable of decontaminating
      these patients. There are, however, no national studies that assess emergency
      department preparedness. The purpose of this survey was to assess the hazmat
      readiness of US Level 1 trauma centers (TCs). All 1996 Hospital Blue Book TCs
      (256) were queried by anonymous survey; 61% (156) responded to the survey. The
      TCs treated 43,046 +/- 28,455 patients (median, 40,500; range, 600 to 220,000);
      15 +/- 29 (median, 6; range, 0 to 200) were hazmat-contaminated. Only 6%
      acknowledged having all necessary equipment required for safe decontamination.
      Many (83%) had hazmat response plans, but few (30%) of these plans were complete.
      Approximately 36% of the staff had received training. Thirteen staff required
      medical attention themselves after rendering care to a contaminated patient. Only
      58% of the TCs performed a single drill. The preparedness of US Level 1 TCs to
      safely decontaminate hazmat patients seems to be inadequate.

PMID- 10914338
TI  - Use of a job-exposure matrix to assess occupational exposures in relation to
      birth defects.
AB  - Accurate exposure assessment remains a challenge in occupational epidemiology. We
      evaluated one approach, use of a job-exposure matrix (JEM), by applying the
      National Institute for Occupational Safety and Health (NIOSH) JEM to a large case
      control birth defects study that included parental occupation information. We
      investigated the JEM exposure predictions in several ways and found that for a
      substantial proportion of the parents in the birth defects study, the JEM yielded
      either no exposure data or nonsense predictions. Among exposure predictions that
      were plausible, most were of low probability. The high probability exposure
      predictions were statistically unstable, and neither low nor high probability
      exposure predictions were reliable. There was considerable discrepancy between
      the JEM predictions and expert assessments for five exposures of interest.
      Application of the NIOSH JEM to the birth defects study database (and probably
      other databases as well) does not provide a useful means of assessing
      occupational exposures.

PMID- 10914339
TI  - Silica, silicosis, and lung cancer: a response to a recent working group report.
AB  - The relationship between crystalline silica and lung cancer has been the subject
      of many recent publications, conferences, and regulatory considerations. An
      influential, international body has determined that there was sufficient evidence
      to conclude that quartz and cristobalite are carcinogenic in humans. The present
      authors believe that the results of these studies are inconsistent and, when
      positive, only weakly positive. Other, methodologically strong, negative studies
      have not been considered, and several studies viewed as providing evidence
      supporting the carcinogenicity of silica have significant methodological
      weaknesses. Silica is not directly genotoxic and is a pulmonary carcinogen only
      in the rat, a species that seems to be inappropriate for assessing particulate
      carcinogenesis in humans. Data on humans demonstrate a lack of association
      between lung cancer and exposure to crystalline silica. Exposure-response
      relationships have generally not been found. Studies in which silicotic patients
      were not identified from compensation registries and in which enumeration was
      complete did not support a causal association between silicosis and lung cancer,
      which further argues against the carcinogenicity of crystalline silica.

PMID- 10914340
TI  - Mortality among three refinery/petrochemical plant cohorts. I. 1970 to 1982
      active/terminated workers.
AB  - This study updates mortality rates for 19,075 active and terminated workers at
      three refinery/petrochemical plants. Mortality rates of the workers were compared
      with both national and state rates. The results indicated deficits of deaths for
      all causes, all malignant neoplasms, and respiratory and prostate cancer. The
      noteworthy finding was a statistically significant increase in leukemia among
      Louisiana male subjects (standardized mortality ratio [SMR], 181; 95% confidence
      interval [CI], 122 to 259), which showed suggestive trends of increasing SMRs
      with increasing tenure. This excess was largely due to increased chronic
      lymphocytic leukemia (SMR, 351; 95% CI, 168 to 645). The rate of kidney cancer
      remained elevated among Louisiana male subjects, but this finding was no longer
      significant, and there were no patterns in SMRs by tenure and latency.
      Mesothelioma was increased at the Louisiana (SMR, 198; 95% CI, 72 to 430) and
      Texas (SMR, 246; 95% CI, 99 to 507) locations. The leukemia findings have
      prompted a study of leukemia incidence at the Louisiana location.

PMID- 10914341
TI  - Mortality among three refinery/petrochemical plant cohorts. II. Retirees.
AB  - This study updates mortality data for 6238 retirees from three
      refinery/petrochemical plants. Almost 90% of the cohort was deceased. Deaths from
      all causes (standardized mortality ratio, 104; 95% confidence interval, 102 to
      107) and all cancers (standardized mortality ratio, 109; 95% confidence interval,
      102 to 116) were elevated. Increased deaths due to kidney cancer, mesothelioma,
      and the category of other lymphohemopoietic cancers also were observed. The rate
      of leukemia was not increased. There was little internal or external consistency
      to support an occupational relationship for kidney cancer, but findings for
      mesothelioma and other lymphohemopoietic cancers are consistent with reports for
      other petroleum cohorts. Analyses by age indicated significantly higher all-cause
      mortality rates among persons retiring before age 65. The results suggest that
      continued surveillance of mesothelioma and lymphohemopoietic cancer malignancies
      in younger workers with more contemporary exposures may be warranted.
      Furthermore, age at retirement should be considered when analyzing occupational
      cohorts.

PMID- 10914342
TI  - Risk-based selection of respirators against infectious aerosols: application to
      anthrax spores.
AB  - This article presents two methods for estimating infection risk among individuals
      wearing air-purifying respirators against airborne pathogens, with the overall
      aim of selecting appropriate respiratory protection. Necessary data inputs are
      the parameters for the ambient pathogen concentration distribution, the
      respirator penetration distribution, and the infectious dose distribution, along
      with the breathing rate, duration of a respirator use period, and the number of
      use periods. The first method assumes that the pathogen does not exhibit a
      cumulative dose effect, whereas the second accounts for a cumulative dose effect.
      The methods are illustrated with hypothetical scenarios involving Bacillus
      anthracis (anthrax) spores. Available data suggest that anthrax spores would
      exhibit a cumulative dose effect for multiple exposures occurring close in time,
      as would likely affect personnel responding to a bioterrorist release. The
      analysis shows that failure to account for a cumulative dose effect when present
      leads to underestimating infection risk. Three types of air-purifying respirators
      are compared for their predicted efficacy in reducing the risk of inhalation
      anthrax. Although uncertainty analyses are not performed, a general conclusion is
      that a full-facepiece powered air-purifying respirator would be the best air
      purifying device for responding to an anthrax spore release. Because such
      respirators would not prevent all personnel from inhaling an infectious dose, it
      would be advisable for users not previously vaccinated against anthrax to receive
      post-exposure prophylactic therapy.

PMID- 10914343
TI  - Development of a screen for predicting clinical outcomes in patients with work
      related upper extremity disorders.
AB  - This study prospectively examined the extent to which a set of medical, physical,
      ergonomic, occupational psychosocial, and individual psychosocial variables would
      predict clinical outcome associated with a diverse set of work-related upper
      extremity disorders in recently diagnosed individuals. This investigation was
      designed to develop a tool for use in a clinical setting to assist in identifying
      patients at risk for poorer outcome. Outcome was measured at 1, 3, and 12 months
      after completing a baseline questionnaire. Outcome status was based on a median
      split of a standardized composite index (symptoms, function, workdays lost, and
      mental health). Logistic regression indicated that predictors of poorer outcome
      at 1 month were: upper extremity comorbidity (risk ratio [RR], 1.58), pain
      severity (RR, 1.45), ergonomic risk exposure (RR, 1.07), low job support (RR,
      1.03), and pain coping style (RR, 1.54). At 3 months, poorer outcome was
      predicted by: symptom severity (RR, 10.46), job stress (RR, 1.20), and pain
      coping style (RR, 1.98). The number of prior treatments/providers (RR, 1.77),
      past recommendation for surgery (RR, 6.43), and pain coping style were found to
      predict poorer outcome at 12 months. Sensitivity and specificity, respectively,
      for the models were 77.4% and 71.8% at 1 month, 80.6% and 82.4% at 3 months, and
      80.6% and 83.3% at 12 months. The results indicate that baseline measures of
      ergonomic and psychosocial stress, pain severity, and pain coping style predict
      clinical outcome at shorter intervals, whereas number of past
      treatments/providers, recommendation for surgery and pain coping style predict
      longer-term outcome. The resulting prognostic screen provides a simple tool that
      assesses the multidimensional nature of work-related upper extremity disorders
      and predicts clinical outcome. Furthermore, the findings suggest the importance
      of early intervention that addresses both physical and psychosocial stressors at
      work. Specific recommendations to reduce the impact of observed risk factors are
      discussed.

PMID- 10914344
TI  - An updated mortality study of workers at a dye and resin manufacturing plant.
AB  - This investigation evaluated the mortality experience of workers at a dye and
      resin manufacturing plant in New Jersey. The retrospective follow-up study
      included 3266 workers employed for at least 6 months at the plant. Plant
      production areas were South Dyes, where anthraquinone dyes and intermediates were
      produced; North Dyes, where azo dyes and intermediates were produced; and
      plastics and additives, where various resins and additives for plastics were
      made. Analyses used standardized mortality ratio (SMRs) to compare the cohort's
      cause-specific mortality rates during 1952 to 1995 with the rates of the New
      Jersey population. There were fewer than expected deaths from all causes combined
      (728 observed vs 810 expected) and similar numbers of observed and expected
      cancer deaths (225 vs 232). Statistically significant work area-specific cancer
      excesses were limited to white men and included an excess of lung cancer in
      Maintenance workers (40 observed vs 26 expected; SMR, 153; 95% confidence
      interval [CI], 109 to 208) and in South Dyes workers (32 observed vs 19 expected;
      SMR, 168; CI, 115 to 237) and an excess of stomach cancer (5 observed vs 1.3
      expected; SMR, 386; CI, 125 to 901), bladder cancer (4 observed vs 0.8 expected;
      SMR, 515; CI, 140 to 1318) and central nervous system cancer (5 observed vs 1
      expected; SMR, 517; CI, 168 to 1206) in North Dyes workers. None of these
      increases was concentrated in work area subgroups with long duration of
      employment and long potential induction time. It was concluded that the excess of
      bladder cancer probably was due to exposure to carcinogenic arylamines at another
      facility, where some employees had worked before coming to the study plant. The
      other cancer increases may be attributable to chance, to uncontrolled confounding
      by smoking, or to an unidentified occupational exposure.

PMID- 10914345
TI  - Patient preference for in-exsufflation for secretion management with spinal cord
      injury.
AB  - An important aspect of respiratory management in patients with acute spinal cord
      injury (SCI) is the elimination of secretions. Methods utilized for secretion
      management in patients with SCI includes endotracheal suctioning and mechanical
      in-exsufflation (MI-E). Surveyed here is a group of patients with SCI who have
      had experience with both endotracheal suctioning and MI-E via tracheostomy, to
      determine patient opinions and experiences regarding the 2 techniques. The survey
      was administered to 18 patients with traumatic SCI, with an average age of 34.
      72% were ASIA A, 22% percent were ASIA B, and 6% were ASIA C, with neurological
      level of injury ranging from C-1-T-3. Results indicate that patients found MI-E
      significantly less irritating (p < 0.001), less painful (p < 0.001), less tiring
      (p = 0.01), and less uncomfortable (p < 0.001) than endotracheal suctioning. In a
      direct comparison, 89% of patients preferred mechanical in-exsufflation to
      suctioning. In addition, 89% of patients found MI-E faster, 78% found MI-E more
      convenient, and 72% found MI-E more effective than suctioning. This study
      demonstrates that all measured aspects of patient experience are more positive
      for MI-E than for endotracheal suctioning.

PMID- 10914346
TI  - Hip joint exposure during ischial pressure sore reconstruction.

PMID- 10914347
TI  - Sigmoid colon rupture secondary to Crede's method in a patient with spinal cord
      injury.
AB  - Crede's method is a manual suprapubic pressure exerted with a clenched fist or
      fingers, used to initiate micturition, in patients with spinal cord injury (SCI)
      who have neurovesical dysfunction. It is usually a benign maneuver unassociated
      with any major complications. This paper will illustrate a case report involving
      a sigmoid colon rupture secondary to Crede's method in a patient with SCI.
      Various techniques of Crede's method are briefly described. It is recommended
      that patients with quadriplegia avoid forceful use of Crede's method, as it may
      cause contusion of the abdominal wall and injuries to internal viscera, possibly
      leading to colonic rupture. It is believed that this is the first reported case
      of such an unusual complication of Crede's method in patients with SCI.

PMID- 10914349
TI  - Intramedullary sarcoidosis presenting as incomplete paraplegia: case report and
      literature review.
AB  - Sarcoidosis is a chronic, multisystem noncaseating granulomatous disease of
      unknown etiology. Sarcoidosis typically presents clinically in individuals
      between the ages of 20 and 40 years. Although sarcoidosis most commonly affects
      the respiratory system, nearly any organ system can be involved. Spinal cord
      involvement by sarcoidosis is a rare event, occurring in less than 1% of patients
      with systemic disease. The case presented is that of a 29-year-old black male
      with benign past medical history who presented with a 6-week history of
      progressive incomplete paraplegia and bowel dysfunction. Magnetic resonance
      imaging revealed an intramedullary mass at the T-4-T-5 levels. The patient
      underwent thoracic laminectomy and debulking of the mass. The pathology was
      consistent with granulomatous disease. Postoperatively, the patient was placed on
      prednisone. He subsequently received comprehensive inpatient and outpatient
      rehabilitation and at present is bowel and bladder continent and ambulating at
      community levels with a rolling walker. The diagnosis of sarcoidosis; potential
      treatment options, including debulking and long-term steroid use; and prognosis
      will be discussed.

PMID- 10914348
TI  - Spinal cord infarction following vertebral angiography: clinical and pathological
      findings.
AB  - Spinal cord damage from radiographic contrast material has been known to occur in
      both spinal and nonspinal angiographic procedures. Reported here is cervical
      spinal cord injury (SCI) during vertebral angiography. During the procedure, the
      patient displayed signs of acute cervical spinal cord irritation that should have
      been taken as a warning of impending injury. Autopsy 9 years later showed
      evidence of central cervical spinal cord necrosis. The pathological findings are
      similar to those seen in animal models of contrast media-induced SCI; and the
      pathophysiological mechanisms of such injury are discussed.

PMID- 10914350
TI  - The Case Western Reserve University hybrid gait orthosis.
AB  - Six individuals with paraplegia and injury levels from C-1 through T-12
      participated in a study to evaluate the functional capabilities of a hybrid gait
      orthotic system. Subjects learned to use a custom-built reciprocal gait orthosis
      without stimulation and with electrical stimulation activating between 4 and 16
      muscles. Outcomes were scored with standard physical therapy measures including
      the Tinetti test, a timed get up and go, Borg rating of perceived exertion, and
      the Functional Index Measure (FIM). Subjects have successfully accomplished sit
      to stand, stand to sit, and walking maneuvers measured for time, speed, and
      distance. Metabolic consumption was measured for walking in the light work region
      of 5.1 to 6.5 metabolic equivalents (METs) 1 MET = 3.5 ml of O2/kg/min with
      hybrid gait orthosis. Perceived exertion as measured with the Borg scale
      indicated that use of the bracing system with functional electrical stimulation
      was "easier" than without stimulation. Subjects using a hybrid system were able
      to walk up to 350 m at average speeds of 0.25 m/s. Walking speeds for 30- and 50
      meter distances reached 0.45 m/s. Additionally, walking distances with
      stimulation were 2 times greater than those of non-stimulated reciprocal gait.
      FIM scores indicated that system users would become slightly more independent in
      mobility. Results were used to determine the most useful brace modifications for
      the next generation of Case Western Reserve University hybrid gait orthoses to
      allow an expanded function that will include stair climbing and side stepping.

PMID- 10914351
TI  - Immune dysfunction and illness susceptibility after spinal cord injury: an
      overview of probable causes, likely consequences, and potential treatments.
AB  - Information contained in the following monographs was presented as a symposium at
      the Annual Conference of the American Paraplegia Society in September 1999.

PMID- 10914352
TI  - Known and plausible modulators of depressed immune functions following spinal
      cord injuries.
AB  - Recent evidence suggests that depression of immune function occurs early after
      spinal cord injury (SCI) and is maintained thereafter. Deviations from immune
      function observed in healthy persons with intact neuraxes include natural killer
      cell number and cytotoxicity, T cell function and activation, macrophage
      phagocytosis, levels of interleukins (IL)-2 and -6, the soluble IL-2R receptor,
      and intracellular adhesion molecules. While a single etiology explaining these
      abnormalities has not been identified, decentralization of the autonomic nervous
      system is the most likely cause. Otherwise, many persons with SCI, who sustain
      episodic autonomic overstimulation, are among the most physically deconditioned
      of all humans, and often select a diet rich in fat and low in protein. All of
      these are associated with suppressed immune function in persons without SCI.
      Those with SCI may also be (over)exposed to drugs and medications that suppress
      immune function, including methylprednisolone administered immediately after
      traumatic injury. No evidence suggests that the immune profiles of persons with
      SCI favor disease and illness resistance. As opportunistic infections of the
      urinary tract, lungs, and skin represent major causes of morbidity for those
      aging with SCI, attention to, or intervention on, immune suppressive states,
      traits, behaviors, diets, and medications may represent a means through which
      host defenses of persons with SCI can be fortified and their illness proclivities
      reduced.

PMID- 10914353
TI  - Influence of neurological level on immune function following spinal cord injury:
      a review.
AB  - Due to the high incidence of lifelong infections in persons with spinal cord
      injury (SCI), the authors examined level of injury-related immune characteristics
      in a cohort of subjects with chronic SCI. Since the sympathetic nervous system
      and the endocrine system are known to be modulators of immune function, one
      possible explanation for heightened incidence of infections includes
      dysregulation of sympathetic outflow tracts in individuals with tetraplegia or
      high paraplegia. Natural killer cell cytotoxicity (NKCC) and bactericidal
      function of circulating neutrophils were assayed in a group of 10 individuals
      with chronic complete cervical SCI, a group of 8 individuals with paraplegia with
      injuries below the main sympathetic outflow (T-10 and below) and a group of 18
      age- and sex-matched controls. In addition, a psychiatric assessment of
      depression was performed as well as assays of pituitary and adrenal functions.
      Analyses revealed no significant differences in immune function between all
      subjects with SCI combined and their matched controls. Further analyses
      stratifying based on presence or absence of sympathetic dysregulation revealed
      significantly impaired phagocytic ability and a trend toward reduced NKCC in the
      group with tetraplegia compared with their controls. Hormonal assays showed that
      dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DS) were
      higher in individuals with tetraplegia than controls, but no such differences
      were observed in individuals with paraplegia compared with their controls. The
      results of this study suggest that individuals sustaining complete cervical SCI
      experience alterations in immune function, while those with lesions at or below T
      10 do not. These findings of level of injury related immune alteration could not
      be explained by mood differences. This paper is a review of previously published
      work and the authors' current thinking regarding increased acquisition of
      infections in this population.

PMID- 10914354
TI  - Review of immune function, healing of pressure ulcers, and nutritional status in
      patients with spinal cord injury.
AB  - The immune, neural, and endocrine systems do not act autonomously; rather,
      multiple communicative pathways exist among the nervous, endocrine, and immune
      systems that facilitate physiological immunoregulation. Patients with spinal cord
      injury (SCI) have decreased natural and adaptive immune responses by 2 weeks
      after injury. In patients with SCI, adrenocorticotropic hormone (ACTH) and urine
      free cortisol levels were increased while zinc and albumin levels were decreased,
      respectively. In addition, the surface markers alpha 2, alpha 3, alpha 4, CD11a,
      CD11b, CD18, CD54, and CD8 found on lymphocytes and alpha 3, alpha 4, CD11a,
      CD18, and CD8 surface markers found on granulocytes were also decreased in the
      patient population. Finally, the adhesion molecules binding ability in the SCI
      group was also decreased when compared with a control group. Overall, the
      investigation showed that patients with SCI have a decreased immune function,
      especially succeeding the SCI injury, an impaired nutrition status, and a
      decreased number of adhesion molecules, all of which contribute to delayed wound
      healing.

PMID- 10914355
TI  - Bacterial interference for prevention of urinary tract infection: an overview.
AB  - Urinary tract infection (UTI) is the most common infection in patients with
      spinal cord injury (SCI) and is a major cause of morbidity and mortality in this
      population. The bladders of patients with SCI, particularly those with indwelling
      bladder catheters, can become colonized by a variety of organisms, including
      those that may, and others that may not, cause symptoms of infection. The latter
      group of bacteria, so-called benign colonizers, are often left untreated because
      they may provide some protection against symptomatic infection with more
      pathogenic bacteria. In recent years, deliberate urogenital tract colonization
      with benign bacterial strains was studied with the objective of offering some
      protection against invasion by uropathogenic strains. When well-characterized
      strains of Lactobacillus sp. were used to colonize the vagina of women prone to
      frequent UTI, a moderate reduction in the rate of recurrent UTI was observed. In
      other studies, a non-pathogenic prototype of Escherichia coli (strain 83,972)
      causing asymptomatic bacteriuria was used for deliberate bladder colonization.
      These preliminary observations encourage the examination of the safety and
      preventive efficacy of this approach in human subjects.

PMID- 10914356
TI  - Diversion colitis in patients with myelopathy: clinical, endoscopic, and
      histopathological findings.
AB  - OBJECTIVE: One of the problems with a diverting colostomy, applied in patients
      with myelopathy for complications of the neuropathic large bowel, is diversion
      colitis. A clinical, endoscopic, and histological survey was conducted to
      describe the problem in these patients. METHODS: 19 patients with myelopathy who
      have had colostomies (68% of those available) participated in the survey. History
      of rectal discharge and perineal ulceration plus colonoscopic and biopsy
      observations were recorded. 20 patients with myelopathy who have not had
      colostomies, with clinically indicated colonoscopic examinations, were compared
      for skin breakdown and endoscopic appearance. RESULTS: 15 patients who had
      colostomies (79%) reported rectal discharge, and 9 (47%) sustained perineal
      ulceration, 2 being recurrent and refractory. None of the 20 patients who had not
      had colostomies had perineal ulceration (p = 0.04). Colonoscopy revealed mucosal
      erythema and friability in 18 patients (94%) with a predominance in the
      rectosigmoid colon. 1 of 20 without colostomy presented with this picture (p <
      0.001). Mucosal biopsies of diverted colon revealed chronic inflammation in all
      patients, severe inflammation in 13 of 19 subjects at < or = 20 cm from the anus,
      and in 3 of 10 at > 20 cm (p = 0.06). No difference in the severity of
      inflammation with time, 0 to 2 years versus > 2 to 18 years post colostomy, could
      be demonstrated. CONCLUSIONS: Diversion colitis is a frequent, persistent, and
      sometimes problematic complication in patients with myelopathy who have also had
      colostomies.

PMID- 10914357
TI  - Paraplegia subsequent to administration of tissue plasminogen activator and
      intravenous heparin following myocardial infarction--a case report.
AB  - A case involving spinal epidural hematoma following tissue plasminogen activator
      and intravenous heparin therapy administered after acute myocardial infarction is
      reported here. The symptoms of spinal epidural hematoma following thrombolytic
      therapy are outlined and a recommended course of action for arriving at a
      definitive diagnosis of suspected epidural hematoma is provided.

PMID- 10914358
TI  - Spinal cord injury: facts and figures at a glance.

PMID- 10914359
TI  - Automatic mode switching variants: dual demand pacing, retriggerable atrial
      refractory periods, automatic mode adaptation, and pseudomode switching.
      Enlightenment or obfuscation?

PMID- 10914360
TI  - Electrophysiological and anatomic heterogeneity in evolving canine myocardial
      infarction.
AB  - Although the heterogeneity of electrophysiological properties is increased after
      myocardial infarction, the degree of this heterogeneity has not been well
      quantitated and its relationship to the histological changes that occur after
      infarction has not been carefully examined. The purpose of the present study was
      to test the hypothesis that alterations in electrophysiological properties in
      healing canine infarction are related to particular histological changes.
      Experimental infarction was produced by left anterior descending coronary
      ligation. Six dogs were used as controls, six were studied 5 days following, and
      six were studied 8 weeks following infarction. Pacing thresholds, effective
      refractory periods, and activation-recovery times were determined at 112 sites on
      the anterior left ventricle using a multiple electrode plaque. Conduction
      velocity, conduction-heterogeneity index--a measure of conduction disturbance-
      and histology of the epimyocardium underlying the plaque were assessed. The
      effective refractory periods and activation-recovery times were greater in both
      infarction groups, most prominently in the subacute group. In subacute
      infarction, significant postrepolarization refractoriness was present. In healed
      infarction, conduction velocity was decreased and the conduction-heterogeneity
      index was increased compared to controls and subacute infarction. Dispersion of
      excitability and repolarization was associated with more extensive local
      scarring. Dispersion of myocardial fiber angles was associated with the
      conduction-heterogeneity index. Some but not all of the electrophysiological
      changes noted in the animals with infarction were also seen in sham operated
      animals. Thus, heterogeneity in repolarization and refractoriness is greatest in
      the subacute phase of myocardial infarction and is associated with the extent of
      local cell death. In contrast, disturbances in conduction are greatest in healed
      infarction and associated with disarray of myocardial fibers.

PMID- 10914362
TI  - Wenckebach upper rate response in single chamber pacemaker.
AB  - The Medtronic Minix pacemaker during normal function in the VVT mode was found to
      exhibit a Wenckenbach upper rate response similar to that of dual chamber
      devices. This behavior occurred only when the upper rate interval was longer than
      the pacemaker refractory period. In a single chamber device this response may
      simulate pacemaker malfunction.

PMID- 10914361
TI  - High rate atrial tachyarrhythmia detections in implantable pulse generators: low
      incidence of false-positive detections. The PA Clinical Trial Investigators.
AB  - Some newer pulse generators have enhanced diagnostic features that provide
      information on the frequency, date, time of onset, and duration of atrial and/or
      ventricular tachyarrhythmias. However, the sensitivity and specificity of device
      based atrial tachyarrhythmia detections may vary and depend, in part, on lead
      position and selected programming parameters. The prevalence of inappropriate
      detections of paroxysmal atrial fibrillation (PAF) was investigated in 97
      patients who received a Thera DR pacemaker 3 months prior to a planned AV node
      ablation. Patients were randomized to no atrial or to rate adaptive atrial pacing
      therapy and followed for 3 months. Following a total AV node ablation, patients
      were randomized to DDDR versus VDD pacing and followed for 1 year. The high rate
      atrial episode diagnostic feature was used for detection of PAF and the
      diagnostic data were retrieved during follow-up visits. Criteria were developed
      to identify oversensing due to near-field P wave detections, far-field R wave
      detections, or competitive atrial pacing as causes of false-positive atrial
      tachyarrhythmia detections. A total of 1,636 detections of PAF were recorded in
      patients preablation. Only 48 episodes (2.9%) were characterized as false
      positive detections; 25 episodes (1.5%) were classified as oversensing, and 23
      episodes (1.4%) were classified as competitive atrial pacing. A total of 3,061
      detections of PAF were recorded postablation. Only four episodes (0.1%) were
      classified as oversensing. Thus, the diagnostic atrial tachyarrhythmia detection
      feature in newer pacemakers is an effective method for evaluating the time course
      of PAF in patients with implantable pulse generators.

PMID- 10914363
TI  - Sensing of atrial fibrillation by a dual chamber pacemaker: how should atrial
      sensing be programmed to ensure adequate mode shifting?
AB  - Patients with atrial fibrillation and a DDDR pacemaker were studied to assess
      mode switching at different atrial sensitivity settings. Thirty-one patients were
      investigated 7 +/- 9 months after pacemaker implantation and 20 of those patients
      were reinvestigated 23 +/- 9 months after implant. Adequate mode switching was
      evaluated by stepwise programming the atrial sensitivity setting from maximal to
      minimal in the bipolar mode. Adequate mode switching was observed in all 31
      patients during the first evaluation. The lowermost sensitivity average allowing
      for mode switching was 1.1 +/- 0.7 mV (range 0.3-4.0 mV). A total of 22 (71%)
      patients demonstrated intermittent mode shifting at sensitivity settings above
      the atrial sensing threshold. In six (19%) patients, the adequate sensitivity
      threshold ranged from 0.3 to 0.5 mV, which did not allow for a two-fold
      sensitivity safety margin. During the second evaluation, adequate mode switching
      was achieved in all 20 patients, the lowermost sensitivity average allowing for
      mode switching being 1.1 +/- 0.7 mV (range 0.3-2.0 mV). A total of 16 (80%)
      patients showed intermittent mode shifting at a sensitivity setting above the
      atrial sensing threshold. In five (25%) patients, the sensitivity threshold
      ranged from 0.3 to 0.5 mV, which did not allow for a two-fold sensitivity safety
      margin. Adequate mode switching was achieved in 31 of 31 patients in response to
      atrial fibrillation on one occasion and in all 20 patients on two occasions. It
      was necessary to program the atrial sensitivity to the highest possible level
      (0.3 mV) to ensured adequate mode switching in all cases.

PMID- 10914364
TI  - Effects of electrical stimulation postcardiomyoplasty in a model of chronic heart
      failure: hemodynamic results after daily 12-hour cessation versus a nonstop
      regimen.
AB  - The hemodynamic effects of cardiomyoplasty (CMP) have been investigated in many
      centers, but the question of whether it is necessary to stimulate the latissimus
      dorsi muscle (LDM) 24 hours a day has not been answered. The main goal of our
      investigation was to determine whether hemodynamic results after CMP were
      impaired when continuous electrical stimulation (ES) was off for 12 hours a day.
      A model of chronic heart failure was created in 12 sheep by performing an
      arteriovenous anastamosis and administering doxorubicin. Two weeks after the
      anastomosis, CMP was performed in eight sheep (experimental series); ES training
      was begun at 2 weeks after CMP. After completion of the initial ES conditioning
      (8 weeks after CMP), one group of sheep continued to receive ES 24 hours daily.
      Another group of sheep had only 12 hours of ES daily. Hemodynamic parameters were
      investigated 2 weeks later with the stimulator turned on and then off. With
      doxorubicin administration, arteriovenous anastamosis created a stable model of
      biventricular heart failure (right atrial pressure 20 +/- 3 mmHg vs 6 +/- 2 mmHg
      at baseline; pulmonary capillary wedge pressure 18 +/- 3 mmHg vs 9 +/- 2 mmHg;
      left ventricular end-diastolic area 15.2 +/- 1.2 cm2 vs 6.4 +/- 0.7 cm2; left
      ventricular ejection fraction 0.38 +/- 0.6 vs 0.65 +/- 0.7). Cardiomyoplasty
      improved hemodynamic status in all eight experimental sheep. However, when the
      investigation was performed with the stimulator off, this improvement was
      statistically insignificant. With stimulation on, there was decreased right
      atrial pressure, pulmonary capillary wedge pressure, left ventricular end
      diastolic volume, and increased left ventricular ejection fraction. With the
      stimulator turned off for 12 hours daily, hemodynamic measurements did not differ
      from data with continuous ES for 24 hours daily. Because hemodynamic results do
      not seem to be impaired, we recommend daily, periodic cessation of stimulation to
      prevent damage to the LDM after CMP.

PMID- 10914365
TI  - Experience with a higher impedance, fixed helix, steroid-eluting pacing lead. The
      SWEET PICOTIP Rx Study Group.
AB  - A higher impedance, steroid-eluting pacing lead was studied in a multicenter
      trial. A total of 132 leads were implanted in 61 patients and the electrical
      characteristics were compared with historical controls. The study lead had a
      lower pacing threshold at 3 months, 0.72 +/- 0.33 versus 1.29 +/- 0.82 in the
      atrium and 0.71 +/- 0.25 versus 1.52 +/- 0.52 in the ventricle (P < 0.01 for
      both). Impedance was significantly higher in the study lead, 923 +/- 133 versus
      719 +/- 109 in the atrium and 980 +/- 235 versus 664 +/- 104 in the ventricle (P
      < 0.01 for both). Sensing was similar for both leads. The study lead's higher
      impedance values and low pacing thresholds combine to reduce pacing system energy
      requirements.

PMID- 10914366
TI  - P wave dispersion on 12-lead electrocardiography in patients with paroxysmal
      atrial fibrillation.
AB  - The prolongation of intraatrial and interatrial conduction time and the
      inhomogeneous propagation of sinus impulses have been shown in patients with
      atrial fibrillation. Recently P wave dispersion (PWD), which is believed to
      reflect inhomogeneous atrial conduction, has been proposed as being useful for
      the prediction of paroxysmal atrial fibrillation (PAF). Ninety consecutive
      patients (46 men, 44 women; aged 55 +/- 13 years) with a history of idiopathic
      PAF and 70 healthy subjects (42 men, 28 women; mean age 53 +/- 14 years) were
      studied. The P wave duration was calculated in all 12 leads of the surface ECG.
      The difference between the maximum and minimum P wave duration was calculated and
      this difference was defined as P wave dispersion (PWD = Pmax-Pmin). All patients
      and controls were also evaluated by echocardiography to measure the left atrial
      diameter and left ventricular ejection fraction (LVEF). There was no difference
      between patients and controls in gender (P = 0.26), age (P = 0.12), LVEF (66 +/-
      4% vs 67 +/- 5%, P = 0.8) and left atrial diameter (36 +/- 4 mm vs 34 +/- 6 mm, P
      = 0.13). P maximum duration was found to be significantly higher in patients with
      a history of PAF (116 +/- 17 ms) than controls (101 +/- 11 ms, P < 0.001). P wave
      dispersion was also significantly higher in patients than in controls (44 +/- 15
      ms vs 27 +/- 10 ms, P < 0.001). There was a weak correlation between age and P
      wave dispersion (r = 0.27, P < 0.001). A P maximum value of 106 ms separated
      patients with PAF from control subjects with a sensitivity of 83%, a specificity
      of 72%, and a positive predictive accuracy of 79%. A P wave dispersion value of
      36 ms separated patients from control subjects with a sensitivity of 77%, a
      specificity of 82%, and a positive predictive accuracy of 85%. In conclusion, P
      maximum duration and P wave dispersion calculated on a standard surface ECG are
      simple ECG markers that could be used to identify the patients with idiopathic
      paroxysmal atrial fibrillation.

PMID- 10914367
TI  - The acute effects of biatrial pacing on atrial depolarization and repolarization.
AB  - Permanent biatrial and/or multisite atrial pacing may prevent atrial fibrillation
      (AF), but the effects on atrial electrophysiology remain incompletely understood.
      Acute biatrial pacing was studied in 20 patients with and 28 without (controls) a
      history of atrial fibrillation and/or flutter. Twelve-lead electrocardiograms
      were recorded during pacing from the high right atrium (RA), from the distal
      coronary sinus (LA), and biatrial pacing. P wave duration was measured in each
      lead and the difference between maximum and minimum P duration was termed P wave
      dispersion. Effective refractory periods (ERPs) were measured during each pacing
      mode. The dispersion of P wave duration was 35 +/- 14 ms in controls and 40 +/-
      29 ms in AF patients (P = 0.17). Compared to RA pacing, LA pacing shortened P
      duration in controls (127 +/- 18 to 107 +/- 16 ms, P < 0.05) and biatrial pacing
      markedly shortened P duration in controls (127 +/- 18 to 93 +/- 14 ms, P < 0.05)
      and AF patients (114 +/- 43 to 97 +/- 21 ms, P < 0.05). P wave dispersion was
      unaffected. In controls, the LA ERP was longer than the RA ERP. This phenomenon
      was not present in AF patients, whose LA ERP was shorter than that of controls.
      Biatrial pacing had no effect on atrial ERPs or the dispersion of atrial
      refractoriness. In conclusion, acute biatrial pacing does not affect atrial
      repolarization but it does cause a marked shortening of global biatrial
      depolarization. Distal coronary sinus pacing produces a shorter P wave than RA
      pacing. There is substantial dispersion in the surface P wave of the
      electrocardiogram, the significance of which awaits further study.

PMID- 10914368
TI  - Effects of aging and gender on QT dispersion in an overtly healthy population.
AB  - The objective of this study was to measure the normal variation of QT dispersion
      (QTd) with respect to age and gender. The QT interval is a measure of the
      duration of ventricular depolarization and repolarization, while the QTd is a
      measure of the variability of the ventricular recovery time. The QTd has been
      suggested as a means of identifying those patients at risk for sustained
      ventricular tachyarrythmias and sudden cardiac death (SCD). A total of 250
      patients (120 women, 130 men; age range 20-86 years) were recruited for this
      study. The QT intervals were measured in each of the 12 standard leads of the
      electrocardiogram. Data are presented as mean (mu) +/- SD. The QTd did not vary
      significantly within the same gender. A significant difference (P < 0.001) was
      noted in QTd between men (age [mu] = 53.3 +/- 15.6 years, QTd = 0.044 +/- 0.019
      s) and women (age [mu] = 52.1 +/- 15.1 years, QTd = 0.034 +/- 0.015 s). Overall,
      men had a greater QTd, while women had a longer QT. In conclusion, we found that
      men had a longer QTd, which may explain the increased risk of SCD. However, women
      have a longer QT interval with a smaller QTd. A longer QTmin, as opposed to a
      longer QTmax, is responsible for the shorter QTd in women. This longer QTmin in
      women may predispose to an increased risk of drug induced torsades de pointes.

PMID- 10914369
TI  - Increased variance of P wave duration on the electrocardiogram distinguishes
      patients with idiopathic paroxysmal atrial fibrillation.
AB  - We hypothesized that the variance of P wave duration (P variance) in the 12-lead
      ECG could reflect the spatial dispersion of P wave duration due to inhomogeneous
      and delayed propagation of sinus impulses in the atria, and moreover could
      present better reproducibility than maximum P wave duration and P wave dispersion
      that have already been used for the prediction of idiopathic paroxysmal AF. We
      also tested a semiautomated PC-based method to improve the accuracy and
      reproducibility of P wave measurements. A 12-lead ECG was obtained from 60
      patients with idiopathic paroxysmal AF and from 50 healthy controls. All ECGs
      were analyzed manually using magnifying lens and calipers, while 20 randomly
      selected ones were scanned and analyzed on screen using common commercial
      software. P maximum, P dispersion, and P variance were all significantly higher
      in patients with paroxysmal AF than in controls. A P maximum value of 110 ms, a P
      dispersion value of 40 ms, and a P variance value of 120 ms2 separated patients
      from controls with a sensitivity of 88%, 83%, and 80%, respectively and a
      specificity of 75%, 85%, and 74%, respectively. The reproducibility of P variance
      was higher compared to P dispersion and P maximum. Finally, the PC-based method
      significantly increased accuracy and reproducibility of P wave measurements.
      Thus, the variance of P wave duration could be a useful ECG marker for the
      prediction of paroxysmal idiopathic AF and the use of PC-based methods may
      enhance the accurate measuring of P wave duration on the ECG.

PMID- 10914370
TI  - Chronic amiodarone effects on epicardial conduction and repolarization in the
      isolated porcine heart.
AB  - Amiodarone is a potent antiarrhythmic agent with complex chronic effects, notably
      on repolarization and conduction, that are not fully understood. Its low
      arrhythmogenic potential has been related to a lack of increase in repolarization
      dispersion. Since its effects are not documented in pigs we conducted a mapping
      study of activation and repolarization in isolated perfused porcine hearts.
      Amio20 female pigs (n = 7) received amiodarone 20 mg/kg per day over 4 weeks
      while Amio50 female pigs (n = 7) received 50 mg/kg per day over 4 weeks.
      Concentrations of the drug encompassed values found in clinical studies. Then,
      activation patterns and activation-to-recovery intervals (ARI) were mapped
      epicardially from 128 unipolar electrograms in isolated perfused hearts in
      corroboration of epicardial action potential recordings. Mean ARI was longer in
      Amio20 experiments compared to the seven control hearts (325 +/- 11 ms vs 288 +/-
      5 ms at 1,000 ms), whereas ARI dispersion was not different, being comprised
      between 7 and 11 ms and generating smooth gradients. In Amio50 experiments, mean
      ARI was further prolonged (390 +/- 10 ms at 1,500 ms) with an exaggerated reverse
      rate dependence concomitant with a depressant effect on the plateau of the action
      potential. Again, ARI dispersion did not differ from controls. Finally, the drug
      depressed the maximal rate of depolarization (Vmax) and slowed conduction in a
      rate dependent and concentration dependent fashion. In conclusion, chronic
      amiodarone induces Class I and Class III antiarrhythmic effects in ventricular
      porcine epicardium that are concentration dependent but does not affect
      dispersion of repolarization. This may partly explain its low arrhythmogenic
      potential.

PMID- 10914371
TI  - Atrial lead placement during atrial fibrillation. Is restitution of sinus rhythm
      required for proper lead function? Feasibility and 12-month functional analysis.
AB  - Unexpected atrial fibrillation (AF) during implantation of an atrial pacemaker
      lead is sometimes encountered. Intraoperative cardioversion may lengthen and
      complicate the implantation process. This study prospectively investigates the
      performance of atrial leads implanted during AF (group A) and compares atrial
      sensing and pacing properties to an age- and sex-matched control group in which
      sinus rhythm had been restored before atrial lead placement (group B). Patient
      groups consisted of 32 patients each. All patients received DDDR pacemakers and
      bipolar, steroid-eluting, active fixation atrial leads. In patients with AF at
      the time of implantation (group A), a minimal intracardiac fibrillatory amplitude
      of at least 1.0 mV was required for acceptable atrial lead placement. In patients
      with restored sinus rhythm (group B), a voltage threshold < 1.5 V at 0.5 ms and a
      minimal atrial potential amplitude > 1.5 mV was required. Patients of group A in
      whom spontaneous conversion to sinus rhythm did not occur within 4 weeks after
      implantation underwent electrical cardioversion to sinus rhythm. Pacemaker
      interrogations were performed 3, 6, and 12 months after implantation. In group A,
      implantation time was significantly shorter as compared to group B (58.7 +/- 8.6
      minutes vs 73.0 +/- 17.3 minutes, P < 0.001). Mean atrial potential amplitude
      during AF was correlated with the telemetered atrial potential during sinus
      rhythm (r = 0.49, P < 0.001), but not with the atrial stimulation threshold.
      Twelve months after implantation, sensing thresholds (1.74 +/- 0.52 mV vs 1.78 +/
      0.69 mV, P = 0.98) and stimulation thresholds (1.09 +/- 0.42 V vs 1.01 +/- 0.31
      V, P = 0.66) did not differ between groups A and B. However, in three patients of
      group A, chronic atrial sensing threshold was < or = 1 mV requiring atrial
      sensitivities of at least 0.35 mV to achieve reliable atrial sensing. Atrial lead
      placement during AF is feasible and reduces implantation time. However, bipolar
      atrial leads and the option to program high atrial sensitivities are required.

PMID- 10914372
TI  - Prospective postmarket device studies versus returned product analysis as a
      predictor of system survival.
AB  - Monitoring and reporting mechanisms are vital tools for clinicians to assess ICD
      system performance over time for optimal patient care. This article explores the
      various reporting mechanisms available to the clinician, both historical and
      current, and compares and contrasts two such methods. The lead survival rates
      obtained by return product analysis (RPA) are compared with those from an ongoing
      prospective chronic study that actively follows patients for clinical ICD system
      failures (Tachyarrhythmia Chronic Systems Study [TCSS]). Examination of available
      data shows that a prospective study such as the TCSS is capable of detecting
      clinically significant adverse events in 2.2% of the 3,958 leads followed. By
      comparison, RPA-based monitoring of the same leads detects "out of specification"
      events in 0.5% of the 78,571 leads followed. Statistical analyses of two separate
      families of leads (RV leads and SQ Patch leads) show that survival rates obtained
      by the two methods begin to differ at approximately 2 years of implant
      experience, with 95% confidence intervals no longer overlapping at 3 years. The
      authors conclude that prospective chronic device studies are a superior tool for
      the ongoing monitoring of implanted device performance compared to RPA-based
      reports.

PMID- 10914373
TI  - Dual demand pacing using retriggerable refractory periods for ventricular rate
      control during paroxysmal supraventricular tachyarrhythmias in patients with dual
      chamber pacemakers.
AB  - The use of dual chamber pacing in patients with atrioventricular block and
      paroxysmal supraventricular tachyarrhythmias may present a clinical dilemma
      because of the rapid and erratic triggering of ventricular pacing. To avoid this,
      a variety of pacing methods have now been described, including the use of
      retriggerable atrial refractory periods or dual demand pacing. This review
      details the use, advantages, and limitations of this poorly understood algorithm
      referred to as "pseudo-mode switching."

PMID- 10914375
TI  - Pitfalls of the concept of incremental specificity used in comparisons of dual
      chamber VT/VF detection algorithms.
AB  - The concepts of incremental specificity and incremental positive predictive
      accuracy (PPA) have been proposed to measure the success of dual chamber
      cardioverter defibrillator (ICD) algorithms for tachyarrhythmia detection in
      improving specificity while maintaining very high sensitivity to detection of
      episodes of ventricular tachycardia/fibrillation (VT/VF). While dual chamber
      VT/VF detection algorithms differ substantially among different ICD
      manufacturers, they all operate as "add-on" features to the single chamber
      elementary detection algorithms that are based on simple criteria of increased
      ventricular rate. The incremental specificity and PPA characterize the
      performance of the dual chamber detection operation in this "add-on" mode, that
      is within a database of rhythm episodes all meet the simple rate-based criteria.
      A statistical model of hypothetical devices has been used to demonstrate that the
      concepts of incremental specificity and PPA are very dependent on the composition
      of the database used to evaluate a particular dual chamber ICD. Because some
      sinus tachycardia and supraventricular tachyarrhythmias with regular
      atrioventricular conduction are more easily discriminated from true VT/VF than
      other supraventricular tachyarrhythmias, the model shows that rather than the
      performance of the dual chamber detection functions, the major contributor to the
      incremental specificity may be the proportion between the "easy" and "difficult"
      supraventricular episodes. The algorithms used by different ICD manufacturers to
      detect tachyarrhythmias based on ventricular rate are known to differ
      substantially in the ability to differentiate true VT/VF from other
      tachyarrhythmias. Consequently, the databases of rhythms against which the
      different dual camber ICDs are tested are also different in composition of
      different types of supraventricular tachyarrhythmias. Therefore, the values of
      incremental specificity and PPA reported by different manufacturers do not have
      an equivalent meaning and do not offer a valid comparison of the true performance
      of different dual chamber ICDs.

PMID- 10914374
TI  - Syncope in a young man.

PMID- 10914376
TI  - Radiofrequency catheter ablation from the left sinus of Valsalva in a patient
      with idiopathic ventricular tachycardia.
AB  - We report the case of a 54-year-old woman with idiopathic VT originating in the
      left ventricular outflow tract. She initially presented with palpitations and
      light-headedness. The morphology of the PVCs exhibited an inferior axis and tall
      R waves were noted in all the precordial leads. Spontaneous PVCs were transiently
      terminated by an intravenous injection of adenosine triphosphate. Radiofrequency
      catheter ablation from the left sinus of Valsalva successfully abolished the PVCs
      and the VT.

PMID- 10914377
TI  - Implantable defibrillator therapy in Naxos disease.
AB  - Naxos disease is a unique form of right ventricular cardiomyopathy with a high
      prevalence of malignant ventricular arrhythmias, including sudden cardiac death.
      As a hereditary systemic disease confined to a small island, it has been closely
      studied over the last 15 years. The implantation of an automatic defibrillator
      provides an alternative form of antiarrhythmic management to improve life
      expectancy in these high risk cardiac patients. We present the first two Naxos
      disease patients with malignant ventricular arrhythmias who had defibrillator
      implantation.

PMID- 10914378
TI  - Automatic pace-sense polarity switch as an indicator of early lead corrosion: the
      usefulness of impedance trend graphing.
AB  - A rate responsive dual chamber pacemaker system (Medtronic Inc.) was implanted
      without complications. At 6-week postimplantation a routine pacemaker check
      showed a spontaneous switch from programmed bipolar pace-sense to unipolar pace
      sense on the atrial and ventricular leads. Pacing and sensing thresholds were not
      significantly changed from implantation. The atrial and ventricular lead
      impedances increased from 680 and 720 ohms at implantation to 1,290 and 2,400
      ohms, respectively. The device was reprogrammed to bipolar pace-sense and the
      continuous lead telemetry trend option was programmed On. Evaluation of the
      system 1 month later revealed a decrease in atrial and ventricular lead
      impedances, 680 and 2,100 ohms, without a change in pace-sense polarity. One
      month later, the lead polarity had again switched from programmed bipolar to
      unipolar pace-sense. The lead trend data revealed stable atrial impedances with
      sporadic increases in the ventricular lead impedance to values > 3,000 ohms. The
      pacemaker lead system was invasively investigated and visible gross corrosion of
      the ventricular lead distal connector pin was discovered.

PMID- 10914379
TI  - Management of atrial arrhythmias secondary to severe congenital heart disease
      with the Atrioverter.
AB  - An atrial defibrillator was implanted in a patient with congenitally corrected
      transposition of the great arteries, associated cardiac abnormalities, and
      persistent atrial arrhythmias. During a 15-month follow-up, 14 of 20 spontaneous
      episodes of his arrhythmias were successfully treated with the device. Two of
      these episodes were converted to sinus rhythm during ambulatory use of the
      device. Successful use of the device required implantation of a third
      defibrillation lead in the persistent left-sided superior caval vein and rigid
      control of congestive heart failure. An atrial defibrillator may be a valid
      treatment option in patients with congenital heart disease crippled by atrial
      fibrillation.

PMID- 10914380
TI  - Coexistent atrioventricular and nodoventricular pathways in a patient with
      hypertrophic cardiomyopathy.
AB  - A 17-year-old girl with concentric hypertrophic cardiomyopathy presented with a
      wide complex tachycardia and underwent electrophysiological study. She was found
      to have an antidromic tachycardia utilizing a decremental atrioventricular fiber
      as the anterograde limb with retrograde conduction occurring through the septum.
      Ablation of a right free-wall pathway rendered tachycardia noninducible, yet
      ventricular preexcitation remained. After ablation there was evidence of a second
      nodoventricular connection. We believe this to be the first report of coexistent
      "Mahaim" fibers; one a decremental atrioventricular connection and the second
      nodoventricular.

PMID- 10914381
TI  - Muscle stimulation related to a nonfunctioning epicardial pacemaker electrode.
AB  - Noninfected retained pacemaker leads produce fewer complications than infected
      electrodes. Epicardial electrodes are rarely used, thus complications associated
      with such electrodes are seldom reported. We report a case with muscle
      stimulation due to a retained epicardial pacemaker electrode.

PMID- 10914382
TI  - Analysis of charges and complications of permanent pacemaker implantation in the
      cardiac catheterization laboratory versus the operating room.

PMID- 10914383
TI  - Recent report of a new technique for left ventricular pacing.

PMID- 10914384
TI  - If you can't stand the heat...

PMID- 10914385
TI  - Don't beam me up

PMID- 10914386
TI  - Uncontrolled burn. The Los Alamos blaze exposes the missing science of forest
      management

PMID- 10914387
TI  - Island survivors

PMID- 10914389
TI  - Magnetic anomalies. What are magnetic fields doing in the middle of nowhere?

PMID- 10914388
TI  - Gene scenes.

PMID- 10914390
TI  - Global positioning. New fossils revise the time when humans colonized the earth.

PMID- 10914392
TI  - The U.S. population race

PMID- 10914391
TI  - More than the best medicine.

PMID- 10914393
TI  - Blue chip

PMID- 10914394
TI  - No resistance. High-temperature superconductors start finding real-world uses

PMID- 10914396
TI  - Circles of trust. How vouching for users beats encryption alone in maintaining
      privacy

PMID- 10914395
TI  - Different stripes. Physicists still struggle to explain high-temperature
      superconductivity

PMID- 10914398
TI  - Fountains of youth. Early days in the life of a star

PMID- 10914397
TI  - How green are green plastics?

PMID- 10914400
TI  - Form from fire

PMID- 10914401
TI  - The universe's unseen dimensions

PMID- 10914399
TI  - Is global warming harmful to health?

PMID- 10914402
TI  - Male sexual circuitry. Working Group for the Study of Central Mechanisms in
      Erectile Dysfunction.

PMID- 10914403
TI  - Birth of the modern diet.

PMID- 10914404
TI  - Focusing in a flash

PMID- 10914405
TI  - How to rear a plankton menagerie

PMID- 10914406
TI  - A fractal guide to tic-tac-toe

PMID- 10914408
TI  - The grand plan

PMID- 10914407
TI  - Laws of calorie counting.

PMID- 10914409
TI  - Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions.
AB  - Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) are
      conditions whose closely related pathology suggests shared pathophysiological
      elements, but whose clinical courses are usually, but not always quite
      dissimilar. The former is largely a disease of adulthood, the latter of
      childhood. Optic neuritis, demyelinative transverse myelitis, and Devic's
      syndrome are neurological syndromes that may occur as manifestations of either MS
      or ADEM. Patients with Miller-Fisher syndrome and encephalomyelradiculoneuropathy
      usually have features suggesting ADEM in combination with acute demyelinative
      polyneuropathy. These various conditions and other forms of ADEM share an
      indistinct border with encephalitides, granulomatous, and vasculitic conditions.
      MS, ADEM, and the pertinent syndromic subtypes, their differential diagnosis,
      treatment, and prognosis are considered in this review. Acute cerebellar ataxia
      is a syndrome that is likely to be pathophysiologically distinct from ADEM,
      although its occurrence as a postinfectious illness suggests a distant kinship.
      It is also reviewed.

PMID- 10914410
TI  - Guillain-Barre syndrome: perspectives with infants and children.
AB  - An acute flaccid paraparesis or ascending quadriparesis in an infant or child
      constitutes a very important pediatric neurology emergency. The Guillain-Barre
      syndrome (GBS) is the most frequent cause. This is primarily an autoimmune, post
      infectious, demyelinating, peripheral nervous system process. A small percentage
      of children develop a primary axonal process not unlike that identified more
      commonly in China. Because of the potential for acute respiratory compromise, any
      child suspected of having GBS needs immediate hospitalization. The major
      considerations in differential diagnosis include transverse myelitis, toxic
      neuropathies, tick paralysis, infantile botulism, myasthenia gravis, and
      dermatomyositis. On occasion, some younger children present with an acute severe
      pain syndrome that may mask as a pseudo-encephalopathy. Another clinical variant
      is the Miller-Fisher syndrome characterized by ataxia, ophthalmoparesis, and
      areflexia. This is associated with a high frequency of the anti-GQ-1-b
      antibodies. Although most children with GBS have a relatively benign clinical
      course, some become very ill and require intubation with intensive care
      monitoring. Immunomodulating treatment should be used for any child who loses the
      ability to walk. To date, no well-controlled study has been completed analyzing
      the relative merits of the two most commonly used therapies, namely
      plasmapheresis or intravenously administered immunoglobulin.

PMID- 10914411
TI  - Autoimmune mechanisms in movement disorders.
AB  - A number of disorders, including childhood-onset obsessive compulsive disorder
      (OCD) and Gilles de la Tourette's syndrome (TS), are known to be neurobiological
      in nature. Both TS and OCD are neuropsychiatric diagnoses that involve congitive
      and perceptual dysfunction in addition to motor and psychiatric manifestations.
      The association of the B-cell marker with both Sydenham's chorea and a group of
      neuropsychiatric disorders, such as OCD, tics, and TS, has been useful as a
      marker in these diseases. This evidence, coupled with the recent finding of anti
      brain antibodies in the sera of these patients, raises a number of interesting
      questions concerning the pathological mechanisms involved in these diseases.
      Thus, further molecular characterization of the brain and streptococcal antigens
      will be crucial to our understanding of the neurophysiological processes involved
      in these disorders.

PMID- 10914412
TI  - Neurology of systemic autoimmune disorders: a pediatric perspective.
AB  - Autoimmune disorders can involve patients of any age and organs of any organ
      system. The central and peripheral nervous systems are frequently among the
      targets of these diseases. Immune dysfunction often presents in childhood or
      adolescence. Among the autoimmune disorders that present during childhood and
      adolescence, systemic lupus erythematosus, dermatomyositis, and Behcet's disease
      affect the nervous system with some degree of frequency. Furthermore, although
      juvenile rheumatoid arthritis only rarely affects the nervous system during
      childhood, it and its adult-onset counterpart may have profound long-term
      neurological consequences. Both symptomatic and pathophysiologically aimed
      therapies are important in the treatment of the nervous system sequelae of
      systemic autoimmune disorders.

PMID- 10914413
TI  - Paraneoplastic syndromes: an unsolved murder.
AB  - With neuroimmunology playing an ever greater role in child neurology,
      paraneoplastic syndromes--uncommon but often devastating complications of cancer-
      are in the forefront. Abnormalities of both humoral and cellular immunity support
      the immunological theory of causation. Through co-complicity of host and tumor
      factors, targets of immunologically mediated injury remote from the tumor may be
      damaged or destroyed, giving rise to discrete neurological deficits. In the
      nervous system, the main targets are neuronal nuclei or cell bodies, structural
      constituents, surface receptors, synapses, and ion channels. The clinical
      syndromes and response to treatment differ substantially between children and
      adults. Current pharmacological and biological therapies, which are nonselective,
      include noncytotoxic and cytotoxic drugs, intravenous immunoglobulins, plasma
      exchange, and immunoadsorption, some chosen for induction and others for
      maintenance. Tumor resection and thymectomy are surgical treatments. Combination
      immunotherapies allow steroid sparing, targeting of more than one immunologic
      effector pathway, and deploy an advantageous mixture of early- and late-acting
      drugs. More selective and efficacious immunotherapies are needed.

PMID- 10914415
TI  - Test-seeking as motivation in volunteer blood donors.

PMID- 10914414
TI  - Exploitation of immune mechanisms in the treatment of central nervous system
      cancer.
AB  - Malignant gliomas are among the most common intrinsic brain tumors of both
      children and adults, and, because of unique aspects of their biology and anatomic
      site, they are the most refractory to conventional therapeutic strategies
      involving surgery, radiotherapy, or chemotherapy. Given the failure of standard
      therapies to improve the outlook of affected patients, significant attention has
      been focused on development of alternative treatments, particularly
      immunotherapy. Attempts have been made to treat gliomas using a variety of
      immunologically based strategies, including passive immunization, adoptive
      cellular immunotherapy, local and systemic delivery of biological response
      modifiers, and vaccination with tumor cells. Although preclinical modeling of
      these therapies provided an impetus for translation of their results into
      clinical protocols, these therapies have failed to yield consistently promising
      results in initial trials. However, significant insights into the immunobiology
      of the central nervous system (CNS) and gliomas have been gained from these
      studies, and have established that a number of immunobiological features of the
      brain and of gliomas themselves may be critical determinants in regulating
      efficacious treatment of these tumors. These include the following: (1) the
      presence of a blood-brain barrier that, although partially disrupted by the
      tumor, functions to exclude elements of the immune system from the tumor or brain
      parenchyma; (2) a lack of organized secondary lymphatic tissues supporting
      efficient immune responses locally in the CNS; (3) low levels of expression of
      major histocompatibility complex proteins in the CNS; (4) an apparent paucity of
      the most efficient antigen-presenting cells; and (5) glioma-derived
      immunosuppressive factors, such as transforming growth factor-beta, that
      interfere with the induction of local as well as systemic immune responses to the
      tumor. Recognition of these factors, and an appreciation of the underlying need
      for and validity of developing immunologically based therapies for gliomas,
      supports continued development of novel immunotherapeutic approaches,
      particularly those attempting to enhance the immunogenicity of glioma cells. This
      review addresses the current state of knowledge regarding the immunobiology of
      gliomas, recent developments in immunotherapy of gliomas, and promising future
      directions for development and implementation of cellular immunotherapy of
      gliomas.

PMID- 10914416
TI  - Variant Creutzfeldt-Jakob disease.

PMID- 10914417
TI  - Autoimmune hemolytic anemia: a history.

PMID- 10914418
TI  - Placental Fc receptors and the transfer of maternal IgG.

PMID- 10914419
TI  - Thrombotic thrombocytopenic purpura: new insights in disease pathogenesis and
      therapy.

PMID- 10914421
TI  - Transfusion medicine in developing countries.

PMID- 10914420
TI  - Allogeneic blood transfusion as a risk factor for the subsequent development of
      non-Hodgkin's lymphoma.
AB  - In summary, it is impossible to reconcile the contradictory results of the
      studies of the association between previous blood transfusion and subsequent
      development of NHL (Figs 1 and 2). Most of the studies were of high quality, and
      the authors discussed the possible sources of bias that might have generated a
      spurious association or concealed a true relationship. Although recall bias,
      detection bias, and allogeneic blood transfusions given because of the onset of
      NHL could be responsible for the reported positive associations, these
      explanations were considered by the investigators, and they seem unlikely.
      Multiple comparisons may account for the association between transfusion history
      and NHL in individual studies, but they are less likely to explain the
      association noted in all the positive studies considered together. Random
      misclassification and Berkson's bias might explain some of the null results, but
      they are unlikely to account for disagreements of the magnitude shown in Figures
      1 and 2. Alexander discussed the superior quality of the design of the case
      control study of Adami et al but was unable to explain the disagreements among
      the reported studies (Figs 1 and 2). He concluded that there is no proof that
      allogeneic blood transfusion does not increase the risk of NHL; one can, however,
      be reassured that the evidence so far points to--at worst--a doubling of risk,
      and--at best--no increase in risk after a previous transfusion. Along these
      lines, Figure 1 shows the results of the 3 cohort studies, which were remarkably
      consistent in reporting a 2-fold increase in the risk of developing NHL after a
      blood transfusion; and Figure 2 shows the results of the 6 case-control studies,
      which usually observed no increased risk. If allogeneic blood transfusion does
      have an immunosuppressive effect, this effect is probably transient and weak,
      compared with the severity of the immunosuppression encountered in the
      posttransplantation situation. Immune impairment may be the common determinant
      for the increased risk of NHL observed in transplanted and transfused patients,
      and--if this were the case--the difference in the duration and intensity of the
      immunosuppressive state would be logically congruent with the observed patterns
      of lymphoma development: that is, the risk of NHL is increased 20- to 120-fold in
      the transplanted patients, as compared with only 2-fold in the previously
      transfused patients. The association between allogeneic blood transfusion and
      subsequent development of NHL is biologically plausible, whether the mechanism is
      transfusion-associated immunosuppression, transmission of oncogenic viruses, or
      viral activation in a setting of transfusion-associated immunosuppression. Also,
      if allogeneic blood transfusion is a risk factor for the subsequent development
      of NHL, the increased use of allogeneic blood transfusion since the 1950s might
      account, at least in part, for the increase in the incidence of NHL over the last
      half of this century. Blood transfusions are commonly used worldwide, and--based
      on at least some studies--they show a weak association with NHL (i.e., at worst,
      a doubling of risk; Fig 1). Common exposures that have a weak association with
      NHL are more likely to account for the current epidemic of NHL in the elderly,
      compared with rare exposures that increase the risk of NHL by manyfold. However,
      no evidence regarding a causal relationship between history of an allogeneic
      blood transfusion and the subsequent development of NHL has been presented. The
      available studies are observational, and they cannot determine whether any
      increase in risk, observed in association with allogeneic blood transfusion, is
      due to the transfusion itself or to other factors occurring in association with
      the transfusion. In conclusion, allogeneic blood transfusion from healthy donors
      may be associated with a small increase in the risk of development of NHL after
      the transfusion. This hypothesis is biologically plausible and is

PMID- 10914422
TI  - HLA antibodies and fetomaternal alloimmune thrombocytopenia: myth or meaningful?

PMID- 10914423
TI  - The ultrastructural and histophotometric study of elastic and collagen fibers in
      type II Ehlers-Danlos syndrome and subclinical forms.
AB  - Skin disorders in type II Ehlers-Danlos Syndrome (EDS) are characterized by signs
      of cutaneous hyperdistensibility, skin and vascular fragility, atrophic scars,
      and articular hypermobility. These features may have less important clinical
      presentation in the intermediate forms of type II EDS. The authors studied the
      ultrastructural and quantitative aspects of elastic and collagen fibers in the
      skin of individuals with subclinical signs of type II of Ehlers-Danlos Syndrome.
      A group of 27 individuals (Group I) with large atrophic scars, articular
      hypermobility of the hands, and cutaneous and vascular fragility were compared
      with 10 healthy individuals. The subjects from both groups were volunteers from
      Hospital das Clinicas da Universidade de Sao Paulo. The elastic fibers did not
      show alterations but collagen ultrastructural abnormalities were seen in diameter
      and curvature, such as torsion, collagen flower-like aspect and discrete mass
      enlargement by histophotometry.

PMID- 10914424
TI  - Mammary "comedo"-DCIS: apoptosis, oncosis, and necrosis: an electron microscopic
      examination of 8 cases.
AB  - The terms apoptosis and necrosis are commonly used to imply two distinct types of
      cell death. Apoptosis reflects a genetically mediated. ATP-dependent form of cell
      death. A passive form of cell death (oncosis) also occurs, often in response to
      some form of injury. Both pathways can lead to necrosis (postmortem autolytic
      cell changes). The nature of intraluminal necrosis in mammary ductal carcinoma in
      situ (DCIS) was evaluated using ultrastructural analysis on paraffin-embedded
      material of 8 cases with "comedo"-DCIS. In each case, intraepithelial
      proliferation zones and intraluminal zones (peripheral and central luminal zones)
      were examined. All cases with "comedo"-DCIS revealed abundant apoptosis,
      characterized by apoptotic cells showing chromatin condensation and margination
      with sharply circumscribed, uniformly dense crescents, as well as cytoplasmic
      condensation. Numerous membrane-bound apoptotic bodies with condensed cytoplasm
      (with or without nuclear fragments) were also observed. The central luminal zones
      of "comedo"-DCIS, however, revealed necrotic debris characterized by severe
      degradative changes, largely devoid of recognizable cell structures. In addition,
      two cases displayed features of oncosis, characterized by nuclear and cytoplasmic
      swelling, vacuolization of cytoplasm, and mitochondrial swelling with occasional
      dense bodies. The results indicate that necrosis (postmortem, secondary
      degradative cell changes) in "comedo"-DCIS is the end result of either apoptosis
      (programmed cell death) alone or a combination of apoptosis and oncosis (passive
      or "accidental" cell death).

PMID- 10914425
TI  - Three-dimensional structure of oncocyte mitochondria in human salivary glands: a
      scanning electron microscope study.
AB  - Oncocytes occurring in otherwise normal human salivary glands were examined by
      scanning electron microscopy after being subjected to a maceration technique that
      removes all soluble cytoplasmic components and leaves only membranes in place.
      The three-dimensional images resulting from this procedure confirm that the
      majority of oncocyte mitochondria have shelf-like cristae that are attached to
      the inner boundary membrane, often by means of tubular structures. In some
      mitochondria, the cristae are digitiform and, when transected, give rise to
      putative vesicles. The oncocytic mitochondria in human salivary glands, by and
      large, lack the structural irregularity that has been reported for these
      organelles occurring in oncocytes in other organs.

PMID- 10914426
TI  - Muscle involvement in rheumatoid arthritis: an ultrastructural study.
AB  - An electron microscopic investigation has been carried out on muscle bioptic
      samples from patients affected by rheumatoid arthritis (RA). This study was
      undertaken to seek further ultrastructural alterations affecting striated muscles
      in RA pathology. Bioptic samples were collected on a total of 30 surgical
      interventions of hip (10), knee (8), and foot (12). This yielded three muscle
      types: gluteus maximus, vastus lateralis, and extensor digitorum communis. Muscle
      samples from 12 patients with no RA stigmata, selected to match RA patients by
      age and gender, constituted the control group. Tissue samples were prepared both
      for conventional histochemical methods and according to conventional electron
      microscopic procedures, including morphometric analysis. Although to a different
      extent in each sample, in muscles from RA vs. controls the authors observed the
      simultaneous presence of discrete muscular alterations such as wider separation
      of myofibrils, myelin figures, dilated sarcotubular system, pleomorphic
      mitochondria, myofibril flaking, and lipofuscin deposition in the subsarcolemmal
      region. In addition to a progressive atrophy, the above findings are suggestive
      of rheumatoid myositis and lend further support to the still poorly documented
      presence of an idiopathic inflammatory myopathy and inclusion body myositis
      associated with RA.

PMID- 10914427
TI  - Brenner tumor of the ovary: a comparative immunohistochemical and ultrastructural
      study with transitional cell carcinoma of the bladder.
AB  - Because of a fancied light microscopic resemblance to transitional epithelium
      (urothelium), Brenner tumor (BT) of the ovary is commonly described as a
      transitional cell neoplasm. An inability to detect a great deal of similarity
      between the two at the ultrastructural level prompted this electron microscopic
      study comparing 3 benign Brenner tumors with normal urothelium and 6 transitional
      cell carcinomas (TCC) of varying histologic grade from the urinary bladder. To
      complement the ultrastructural observations, the immunophenotype of 8 benign BTs
      was evaluated together with that of 12 TCCs of the bladder using antibodies to
      thrombomodulin (TM), cytokeratin 20, cytokeratin 7, and carcinoembryonic antigen
      (CEA), all of which have been shown to react with TCCs of urothelial origin. At
      the ultrastructural level, there was only limited evidence of a morphologic
      likeness between the epithelial cells of BTs and those of the benign or
      neoplastic urothelium. The immunophenotype of the two tumors also differed
      significantly in that there was no reactivity for TM or cytokeratin 20 in the
      BTs, while these markers were expressed in the TCCs. Both BTs and TCCs were
      positive for cytokeratin 7 and may express CEA.

PMID- 10914428
TI  - Computer-assisted analysis of radial symmetry in human airway epithelial cilia:
      assessment of congenital ciliary defects in primary ciliary dyskinesia.
AB  - The ultrastructural analysis of cilia and diagnosis of primary ciliary dyskinesia
      (PCD) in biopsies of airway epithelium is sometimes confounded by poor sampling,
      inconsistencies in tissue quality and processing, and other technical problems.
      Although clinical findings may lead to a presumptive diagnosis, ultrastructural
      analysis of ciliary axonemes is the standard for confirmation of PCD. The
      ultrastructural features of the cilium when viewed in cross section by
      transmission electron microscopy confer a radial symmetry to the axoneme. Current
      digital image processing techniques can be applied to such images to reinforce
      signal, diminish noise, and confirm consistency of position of axonemal
      structures, a process that can augment ultrastructural analysis for PCD. In this
      study, computer-assisted digital image processing was used to evaluate cross
      sections of cilia in airway epithelial biopsies from patients previously
      diagnosed with PCD as well as in control subjects with normal cilia. These
      studies supported the original diagnoses and provided some new insights into
      axonemal organization in PCD. This technique is simple and may be useful in
      providing a supporting means for confirming or ruling out a diagnosis of PCD in
      cases that appear equivocal.

PMID- 10914429
TI  - Subcellular distribution of urokinase and urokinase receptor in human neutrophils
      determined by immunoelectron microscopy.
AB  - A high-affinity receptor for urokinase-type plasminogen activator (uPAR) has been
      identified on the plasma membrane of a number of different cell types, and has
      been shown to be important for plasminogen activation, cell adhesion, and
      possibly signal transduction. uPAR and uPA cosediment with secretory vesicles and
      specific granules by subcellular fractionation and translocate to the plasma
      membrane upon activation of neutrophils. Here the subcellular distribution of
      uPAR and uPA is studied by electron microscopy of neutrophils using immunogold
      double labeling for uPAR and uPA and a set of markers for well-defined subtypes
      of granules: matrix metalloproteinase type-9 (MMP-9) for gelatinase granules,
      lactoferrin (LF) for specific granules, and myeloperoxidase (MPO) and neutrophil
      elastase (NE) for primary granules. With this technique uPAR colocalizes with uPA
      in 71% of labeled granules. In granules containing uPAR the degree of
      coexpression with MMP-9, MPO and NE was 19, 66, and 74%, respectively. In
      granules labeled for uPA the corresponding overlap with MMP-9, MPO and NE was 24,
      64, and 51%, respectively. Low levels of co-localization were found for uPAR and
      LF (7%) and for uPA and lactoferrin (5%). The results indicate that uPAR and uPA
      are present in gelatinase granules and primary granules, but rarely in specific
      granules. The demonstration of uPAR and uPA in primary granules is of particular
      interest, and may indicate that uPAR and uPA participate in the activation of
      latent hepatocyte growth factor of neutrophils.

PMID- 10914430
TI  - Ultrastructure of the blood and lymphatic capillaries of the respiratory tissue
      during inflammation and endobronchial laser therapy.
AB  - For wide application of low-energy laser irradiation in the pulmonary clinic,
      study of the structural basis of the therapeutic effect is necessary. The aim of
      this research is to describe the structural changes of the blood and lymphatic
      capillaries in the respiratory tissues during inflammation and following laser
      biostimulation. Comparative ultrastructural study was carried out on 127 open
      respiratory biopsy specimens from 45 patients with infectious-destructive lung
      diseases. These patients were divided into two groups, depending on tactic of pre
      operative therapy: patients treated by only traditional anti-inflammatory
      measures and patients receiving additional laser therapy. Heightened permeability
      of the blood capillary endotheliocytes was noted as the initial stage in the
      development of the inflammatory reaction. Intensification of the process of
      permeability is accompanied by interstitial edema, deformation of the
      interalveolar septa, and structural disorganization of alveolar epithelium cells.
      Local lesions of microcirculation result in tissue hypoxia and induce processes
      of fibrosis. Laser biostimulation promotes reversion of the inflammatory process
      and stabilizes fibroplastic processes. Basic principles of pathogenetic therapy
      were stated. It was shown that low-energy laser irradiation satisfies these
      requirements as an additional method in the therapy of destructive lung diseases.

PMID- 10914432
TI  - Unique cellular features in a testicular plasmacytoma.
AB  - A case of testicular plasmacytoma is described at the light and fine structure
      level. The patient was a 54-year-old male with a history of multiple myeloma. The
      testicular tumor was restricted to an interstitial space growth. Plasma cells
      varied in differentiation with few obtaining the cartwheel nucleus and prominent
      Golgi of connective tissue plasma cells. Cytoplasmic inclusions were
      characteristic of most cells and a large number of intranuclear inclusions were
      present. To our knowledge, this is the first report of such inclusions in the
      cells of a testicular plasmacytoma. Their significance in cases of end stage
      myeloma is discussed.

PMID- 10914431
TI  - Differential diagnosis, prognostic factors, and clinical treatment of
      proliferative Brenner tumor of the ovary.
AB  - Brenner tumors are rare ovarian tumors displaying benign, borderline or
      proliferative, and malignant variants. The case of a 63-year-old woman with a
      proliferative Brenner tumor is presented and the histomorphological differential
      diagnosis of this tumor entity is compared to that of its benign and malignant
      counterparts. Light microscopy, immunohistochemistry, and electron microscopy
      were performed to allow discrimination from the other subtypes. Despite a
      considerable overlap of pathological features the differential diagnosis of
      proliferative Brenner tumor could be established. Electron microscopy allowed
      assessment of characteristic infoldings of the nuclear membrane that proved to be
      a valuable ultrastructural criterion. Considering that the vast majority of
      Brenner tumors are benign, precise identification of the small proportion of
      malignant tumors allows the extent of surgical therapy to be adapted.

PMID- 10914433
TI  - The future, it is an idea whose time has come.

PMID- 10914434
TI  - Accelerated growth and improved nutritional status after recombinant human growth
      hormone (rhGH) therapy in uremic children.
AB  - The effect of recombinant human growth hormone (Norditropin, Novonordisk) was
      studied in 6 children (4 boys and 2 girls) on maintenance hemodialysis, age 13.8
      (range 11-17) years. The recombinant human growth hormone (rhGH) was given in a
      dose of 4 IU/m2/day s.c. Height velocity was followed 6 months before therapy
      (washout period) and 6 and 12 months later. Growth was estimated by use of
      Holtain stadiometer in the same conditions and by the same investigator.
      Nutritional status was assessed by anthropometric measurements including triceps
      skinfold thickness (TST), midarm muscle circumference (MAMC), and lean body mass
      (LBM), as well as serum albumin concentration. The mean height velocity increased
      from 1.67 +/- 0.98, before therapy to 3.33 +/- 1.25 and 6.70 +/- 0.9 cm 6 and 12
      months after therapy, respectively (p < 0.001). Body weight also increased during
      the treatment period from 29.45 +/- 5.24 to 30.96 +/- 6.4 and 31.68 +/- 6.42 kg
      (p < 0.02) and so did body surface area from 1.01 +/- 0.12 to 1.07 +/- 0.13 and
      1.15 +/- 0.1 m2 (p < 0.001). LBM increased from 26.8 +/- 5.4 to 29.85 +/- 6.42
      and 31.1 +/- 7.01 kg 6 and 12 months after therapy (p < 0.001). There was a
      decrease in TST from 7.35 +/- 1.8 to 6.8 +/- 2.18 and 6.8 +/- 2.4 mm (p < 0.3,
      NS), and an increase in MAMC from 15.15 +/- 2.42 to 16.1 +/- 2.4 and 17.63 +/-
      2.6 cm 6 and 12 months after therapy (p < 0.001). Serum albumin concentration
      increased from 33.5 +/- 1.22 to 36.0 +/- 2.4 and 38.66 +/- 1.03 g/L (p < 0.001).
      Nutrition parameters confirmed the beneficial effect of rhGH therapy. The authors
      recommend rhGH therapy in uremic children with growth retardation as well as in
      any case of malnutrition in these patients.

PMID- 10914435
TI  - Transcranial Doppler sonography in patients with Meniere's disease.
AB  - The aim of the study was to assess the correlation between pathologic
      vertebrobasilar (VB) findings obtained by the method of transcranial Doppler
      (TCD) sonography and hearing disorders in Meniere's disease patients. The
      manifestations of Meniere's disease were analyzed in 65 patients and correlated
      with transcranial Doppler of vertebrobasilar circulation. Control group consisted
      of 50 patients with cardiovascular dysfunction who had no hearing loss, tinnitus
      or vertigo, who were submitted to TCD examination. The control group of patients
      with cardiovascular dysfunction did not completely match the study group of
      patients with Meniere's disease. Statistical analysis showed a direct statistical
      significant correlation between the pathologic TCD findings of vertebrobasilar
      circulation and Meniere's disease. According to abnormal findings of TCD in
      27.69% patients, we think that 28% of patients with Meniere's disease suffer from
      insufficient supply of the vertebrobasilar circulation. TCD is an objective
      method of choice for the vascular diagnosis of hearing loss in patients with
      Meniere's disease.

PMID- 10914436
TI  - Acute acalculous cholecystitis in patients with surgical acute renal failure.
AB  - Acute acalculous cholecystitis (AAC) developed in 11 (7.7%) of 143 patients with
      surgical acute renal failure (ARF) who had no prior biliary tract disease. The
      cause of this potentially fatal complication is multifactorial and include
      trauma, previous surgery, sepsis, intermittent positive pressure ventilation,
      total parenteral nutrition, multiple transfusions, hypotension, and opiate
      sedation. The diagnosis of AAC was based on clinical suspicion, ultrasound
      scanning, and laboratory tests (leukocyte count, liver enzymes, bilirubin and C
      reactive protein). All our ARF patients with AAC were receiving antibiotics at
      the time of diagnosis. Five patients were treated conservatively and six
      underwent cholecystectomy. The mortality rate in our ARF patients with AAC was
      45.5%, and was not significantly different from than in ARF patients without AAC.
      The diagnosis of AAC should be made early, and judicious management (conservative
      or surgical) decreases its role as a contributory factor to the mortality in ARF
      patients.

PMID- 10914437
TI  - Are convective methods superior to diffusive dialytic methods?
AB  - The principle of convective elimination is the passage of solutes through the
      membrane carried by water flux, so the elimination of all substances for which
      membrane is permeable is equal to water. This results in uniform clearances of
      small, medium and large molecules. Dialytic methods with exclusive or
      considerable convective elimination are hemofiltration, hemodiafiltration and
      high-flux hemodialysis. Only by convective methods, middle (MM 300-15,000 D) and
      large molecules (MM > 1-15,000 D) are cleared. Standard low-flux hemodialysis
      does not eliminate a considerable amount of medium and large molecules, in
      contrast to outstanding efficiency in small molecule removal. Clinical
      significance of larger molecule removal was analyzed in 4 studies prominent for a
      great number of patients included, very long observation times, or prospective,
      multicentric randomized design. In 3 studies, dialytic methods with convective
      elimination were connected with a mortality decrease by 10% to 39% (statistically
      significant in 2 studies). Dialysis amyloidosis morbidity was lowered by 42%-50%
      when convective methods were used. Results of the presented studies support the
      conclusion that dialytic methods with convective elimination are beneficial for
      survival and prevention of dialysis amyloidosis, irrespective of the biochemical
      characteristics and complement activation by the membrane used.

PMID- 10914438
TI  - The treatment of pilonidal disease of the sacrococcygeal region by the method of
      limited excision and open wound healing.
AB  - Results of the surgical treatment of the pilonidal disease of the sacrococcygeal
      region in correlation with anaerobic infection are analyzed. Fifty patients with
      the disease recurrence (group A) and fifty patients presenting for operative
      treatment for the first time (group B) were observed. Twenty-five patients from
      group B were operated on by the method of limited excision and wound healing by
      open granulation and the other half were operated on by the method of excision
      and primary suture. The material for bacteriologic examination was obtained
      during the operative procedure. All patients underwent control examination at
      twelve months after the surgery. Recurrence was found in three (6%) group A
      patients and two (8%) group B patients operated on by the method of excision and
      open wound healing. Perioperative bacteriologic analysis showed anaerobic
      colonization in all study patients. Among the patients operated on by the method
      of excision and primary suture, recurrence was recorded in six (24%) cases.
      Bacteriologic analysis pointed to anaerobic colonization in five, and to aerobic
      colonization in only one patient. The significantly lower recurrence rates
      recorded with the method of limited excision and wound healing open granulation,
      were explained by favorable conditions for healing in such a wound (reduced
      conditions for anaerobic infection) compared to wound healing after excision and
      primary suture.

PMID- 10914439
TI  - Coffee and health in the elderly.
AB  - Coffee is a very attractive but not a unique drink. There are various types of
      coffee, e.g. Arabica, Canephora, and Robusta. In addition, various coffee blends
      containing several coffee types of different origin are offered in coffee-houses
      in Croatia and worldwide. These coffee blends can differ substantially according
      to their components, especially to the proportion of caffeine. Caffeine is the
      major coffee constituent which the coffee tolerance or intolerance depends on. In
      a healthy liver, the majority of caffeine is degraded by the hepatic microsomal
      enzymatic system. Caffeine is mostly degraded to paraxanthine substances,
      partially to theobromine and theophylline, and a small amount of unchanged
      caffeine is excreted by urine. Therefore, the metabolism of caffeine depends on
      the state of this enzymatic system of the liver. Elderly individuals with a
      depleted enzymatic system do not tolerate coffee with caffeine. They are
      recommended to take decaffeinated coffee, and this only if their stomach is
      healthy, because both decaffeinated coffee and coffee with caffeine cause
      heartburn. Moderate amounts of coffee (50-100 mg of caffeine or 5-10 g of coffee
      powder a day) are well tolerated by a majority of elderly people, who enjoy to
      meet and chat over a cup of coffee. Excessive amounts of coffee, however, can in
      many individuals cause very unpleasant, exceptionally even life-threatening side
      effects. Therefore, elderly persons are recommended to take moderate amounts of
      coffee which will not cause any health impairments.

PMID- 10914440
TI  - On the development of the Rebro Center for Neuromuscular Diseases.

PMID- 10914441
TI  - Breast symptoms. Why do women delay seeing a GP?

PMID- 10914442
TI  - What is the core business of the general practitioner?

PMID- 10914443
TI  - Obstetric medicine--a new subspecialty.

PMID- 10914444
TI  - Chronic fatigue syndrome.

PMID- 10914445
TI  - Infectious diseases in the 21st century. Are we entering the hot zone?
AB  - BACKGROUND: The emergence and re-emergence of several infectious diseases in the
      latter part of the 20th century has created considerable concern, but what real
      impact will these and other infectious diseases have in the 21st century?
      OBJECTIVE: To assess trends in infectious disease mortality, both globally and
      within Australia. RESULTS: Mortality related to infectious disease has declined
      throughout the 20th century in both developed and developing regions. In
      Australia, over the period 1979-1994 infectious disease mortality declined 17%,
      with similar trends seen in several other developed countries. In contrast, over
      a similar period infectious disease mortality increased in the United States by
      approximately 40%. Despite an escalating global HIV epidemic and continuing high
      tuberculosis incidence, infectious disease mortality is projected to decline
      further in the early part of the 21st century, in developed and developing
      regions. By 2020 an infectious disease category will not appear in the top 10
      causes of death in developed regions or top five causes of death in developing
      regions. CONCLUSION: Infectious disease mortality is likely to continue its
      overall decline well into the 21st century.

PMID- 10914446
TI  - A rash of exanthems. How they affect children and pregnant women.
AB  - BACKGROUND: Viral exanthems are a common problem for children, particularly
      during preschool years. Many of these infections have a dramatic impact on
      siblings, parents and other contacts. There may also be particular ramifications
      for pregnant contacts. OBJECTIVE: To discuss some of the most common viral
      exanthems affecting children, in terms of the epidemiology, clinical features,
      diagnosis, and the management of both the patient and the contacts. DISCUSSION:
      Recommendations are made for measles, rubella, parvovirus and varicella regarding
      immunisations, use of immunoglobulin, serological diagnosis and management of
      pregnant contacts.

PMID- 10914447
TI  - Community acquired pneumonia. A perspective for general practice.
AB  - BACKGROUND: Community acquired pneumonia (CAP) occurs in approximately two per
      1000 of the adult population per year. About 2% of adult overnight hospital
      admissions are due to CAP and there is a continuing mortality rate of 7-10%.
      OBJECTIVE: To present an approach for the community and hospital assessment and
      management of CAP based on current concepts and evidence. DISCUSSION: Clinical
      and radiological assessments are unable to identify the nature of the causative
      organism. However, knowledge of the patient risk profile and a clinical severity
      assessment enable appropriate management decisions to be made. Early antibiotic
      therapy according to the guidelines and appropriate supportive management should
      reduce CAP mortality. It is essential that the CAP patient is followed to ensure
      radiological resolution. The incidence of community acquired pneumonia (CAP) can
      be reduced by rigid application of National Health and Medical Research Council
      (NH&MRC) vaccination recommendations for pneumococcal and influenza immunisation.

PMID- 10914448
TI  - HIV risk evaluation.
AB  - BACKGROUND: Australia enjoys good control of human immunodeficiency virus (HIV)
      by world standards and HIV testing is becoming an increasingly integral part of
      general practice. Nevertheless, HIV testing remains charged both emotionally and
      medicolegally. OBJECTIVE: To outline the importance of: determining why a patient
      is requesting an HIV test; helping establish his or her risk of infection; and
      tailoring counselling interventions. CONCLUSION: Isolated high risk exposure to
      HIV may be grounds for postexposure prophylaxis. Other issues frequently arise
      out of HIV risk assessment that represent a greater hazard to the patient than
      HIV. The general practitioner is ideally placed to prioritise and deal with
      sexual health and infection issues on an individual basis.

PMID- 10914450
TI  - Not every child who coughs has asthma.

PMID- 10914449
TI  - Angiotensin receptor antagonists.
AB  - BACKGROUND: Angiotensin receptor antagonists are a relatively new class of
      cardiovascular drugs for which the clinical application has not yet been
      completely defined. OBJECTIVE: This article reviews the pharmacology of the
      various angiotensin receptor antagonists available in Australia, including their
      mode of action, side effects and potential drug interactions. DISCUSSION:
      Angiotensin receptor antagonists are effective drugs for the treatment of mild to
      moderate hypertension which have a side effect profile similar to placebo. Their
      role in the management of hypertension remains to be defined, but they are of
      particular use to patients who are intolerant of ACE inhibitors because of cough.
      It is uncertain at the present time whether the benefits of ACE inhibition in
      other disorders such as congestive heart failure and following myocardial
      infarction will be similar for angiotensin receptor blockers.

PMID- 10914452
TI  - Patient education. Keeping your patients active. The gaffer and the go far.

PMID- 10914451
TI  - Managing depression in pregnancy.
AB  - BACKGROUND: There is increasing awareness of depression in the community, and a
      realisation that it is common and of particular importance in pregnancy where the
      welfare of both the fetus and the child must also be considered. OBJECTIVE: This
      paper looks at the management dilemmas that face the general practitioner when
      someone diagnosed with depression either becomes, or is already pregnant.
      Teratogenicity, and effects of medication at term and in breast milk are
      discussed, as well as the risks of failing to treat. DISCUSSION: Medication when
      required should be kept to the minimum dose needed to adequately treat the
      symptoms, and reduced where possible, towards term. Antidepressants have no
      apparent teratogenetic effects but subtle effects cannot be excluded. Mood
      stabilisers are more likely to have teratogenic effects and should in general be
      avoided in pregnancy. Management needs to involve both the woman and her partner
      in decisions and be ongoing; failure to adequately treat has significant
      ramifications for both mother and child.

PMID- 10914453
TI  - Osteoarthritis. Responding to the patient's needs.

PMID- 10914454
TI  - Palpitations in a young man.

PMID- 10914455
TI  - Medial forefoot pain.

PMID- 10914456
TI  - The rule of nature.

PMID- 10914457
TI  - Advance health directives. Implications for the GP.

PMID- 10914458
TI  - Advance health care planning and the GP. Is it time to move forward?
AB  - AIM: Legislation relating to advance health care planning was introduced into
      Queensland in 1998. All states and territories apart from Western Australia, New
      South Wales and Tasmania now have legislation relating to this issue. The aim of
      this pilot study was to: determine current usage of advance health directives
      (AHDs) in an individual general practice; and encourage appropriate use of AHDs
      in general practice. METHOD: One hundred clinical records were audited for
      evidence of advance health care planning and 100 adult patients were surveyed
      regarding advance care preferences. RESULTS: One percent of clinical records
      showed evidence of advance health care discussion and 5% of those surveyed stated
      they had a current AHD. Only 10% of those surveyed were aware of AHDs; 70% wanted
      to know more about them; 83% wished family members to be substitute decision
      makers regarding health matters if the individual was too ill to be involved; 54%
      nominated doctors to be among their preferred decision makers. CONCLUSIONS: Lack
      of familiarity with advance health care planning options was very common, however
      most patients wished to be involved in their own advance health care planning or
      wished to involve a family member. Legislation now exists in the majority of
      states and territories for this to occur. General practitioners could assist by
      having suitable information available in waiting rooms and including discussion
      in consultations where appropriate.

PMID- 10914459
TI  - Vaccination of cattle workers at risk of Q fever on the north coast of New South
      Wales.
AB  - BACKGROUND: Q fever is the most common zoonotic disease of livestock handlers and
      abattoir workers in rural Australia. AIM: This study aimed to measure the rate of
      pre-existing immunity to Q fever among cattle or saleyard workers on the north
      coast of New South Wales (NSW). METHOD: Participants were screened for complement
      fixation (CF) antibodies and returned one week later for results when a dose of Q
      fever vaccine was given if serum and skin tests were negative. RESULTS: Over a 24
      week period 1417 persons were tested. Of these, 394 had positive CF antibodies, a
      positive skin test or both; 987 were vaccinated with Qvax; 3.1% were lost to
      follow up. DISCUSSION: Over 27% of cattle workers had pre-existing immunity to Q
      fever, indicating this population is at significant risk of infection. General
      practitioners working in high risk communities should routinely test and
      vaccinate patients at risk of Q fever.

PMID- 10914460
TI  - Action orientated research. Can it help resolve gaps in general practice
      knowledge?

PMID- 10914461
TI  - Diabetes mellitus in primary aldosteronism.
AB  - BACKGROUND: Information concerning diabetes mellitus associated with primary
      aldosteronism is scarce. OBJECTIVES: To determine the prevalence of diabetes
      mellitus in its two main pathogenetic forms of primary aldosteronism and to
      evaluate its association with several clinical variables. PATIENTS: Fifty in
      patients (31 female and 19 male, aged 16-66), diagnosed during the years 1980
      1998 as aldosterone producing adenoma (n = 26) or as idiopathic
      hyperaldosteronism (n = 24). METHODS: Morning fasting plasma glucose was measured
      by glucoso oxidase method in all patients. In the presence of higher values,
      confirmatory measurements were performed on the next day. The results were
      evaluated retrospectively by the diagnostic criteria of American Diabetes
      Association, 1997. Statistical significance of the association between diabetes
      mellitus and clinical variables was evaluated by chi-square test. RESULTS:
      Diabetes mellitus was ascertained in 6 patients out of 50 (12%; interval of 95%
      confidence 5-24%). Diabetes was accompanied significantly more often with
      idiopathic hyperaldosteronism (10-47%) than with aldosterone producing adenoma (0
      13%). Patients with the family history of diabetes suffered more often (9-76%)
      from this disease than those without the history (1-19%). Obesity, longer (> 5
      years) duration of hypertension and hypokalaemia did not affect the occurrence of
      diabetes. CONCLUSIONS: The occurrence of diabetes in primary aldosteronism was
      connected significantly with its idiopathic subtype and positive family history
      of diabetes. (Tab. 2, Ref. 11.)

PMID- 10914462
TI  - Ruptured abdominal aortic aneurysm--outcomes in the last ten years.
AB  - Ruptured abdominal aortic aneurysm (AAA) remains to be represent a common and
      highly lethal problem. We reviewed the records of 92 patients (73 men and 19
      women) operated on for ruptured infrarenal AAA within the past 10 years (January
      1989 to October 1999) in the 2nd Department of Surgery in Brno, Czech Republic.
      The mean age was 71 years (range 57 to 92 years). Only 10 patients (10.9%) were
      known to have an AAA before the rupture. Preoperative systolic blood pressure
      below 90 mmHg was present in 70 patients (76%) and 15 patients (16.3%)
      experienced cardiac arrest before surgery. The in-hospital mortality rate was
      47.8% (44 patients). Among the total of 92 patients, haemoperitoneum was
      discovered only in 30 patients (32.6%) with the mortality rate of 40% (12
      patients). In 62 patients (67.4%) also hemoperitoneum was present, the mortality
      rate was 51.6% (32 patients) in these patients. Multiorgan failure due to an
      irreversible hemorrhagic shock was the main cause of death in 23 patients (25%).
      Further causes were: heart failure--8 patients (8.7%), pulmonary complications--5
      patients (5.4%), renal failure--4 patients (4.3%), bleeding--3 patients (3.3%),
      and sepsis--1 patient (1.1%). The patient's prognosis depends on early
      diagnostics and on the quality of peroperative and postoperative care. (Tab. 2,
      Ref. 8.)

PMID- 10914463
TI  - [Borrelia burgdorferi antibodies in scleroderma circumscripta, lichen sclerosus
      et atrophicus, erythema nodosum, granuloma annulare, erythema annulare and
      chronic urticaria].
AB  - OBJECTIVES: The role of B. burgdorferi in the etiology of sclerodermia
      circumscripta (SC) and lichen sclerosus et atrophicus (LSA) are is reported in
      numerous, however controversial studies. The objective of our study is to
      approximate the solution of the given problem and to widen these consideration by
      other diagnoses with multifactorial and unclear etiology such as erythema nodosum
      (EN), granuloma anulare (GA), erythema anulare (EA) and urticaria chronica.
      MATERIAL AND METHODS: 124 probands were divided into groups according the
      diagnoses presented above and compared with the negative control group of 131
      probands with dermatologic diagnoses, in which the etiologic agent of B.
      burgdorferi was not assumed and positive group of 55 probands with lyme
      boreliosis. Indirect immunofluorescent test was used to find out the tieter of
      antibodies against B. burgdorferi in all groups by using the endemic strains as
      antigens, which has caused a higher value of the so-called cut-off. RESULTS: The
      negative control had a positive titer in 44 cases (n = 131, i.e. in 33.6%). The
      positive titer was found in 11 probands from the SC group (34.4% =, n = 32), 5
      probands in LSA (71.4%, n = 7), 9 probands in the EN group (64.3%, n = 14), 6
      probands in the EA and GA groups (42.3%, n = 14) and 19 probands in the group of
      urticaria chronica (33.3%, n = 57). CONCLUSION: We assume that in the probands
      with high titers of antibodies, B. burgdorferi could play a role in the etiology
      of the given diseases titers of antibodies against B. burgdorferi. The draft
      problem could be solved by modern method including PCR with the use of several
      primers focused on different antigens regarding the certain epidemiologic
      regions. (Fig. 7, Ref. 17.)

PMID- 10914464
TI  - [Meningioma of the clivus].
AB  - Clivus meningeoma is a relatively rare tumor with difficult surgical accession.
      Large and giant tumors acquire a very close relation to the brain stem, cranial
      nerves and brain vessels. In 10 our of 13 patients, the large tumor diameter
      exceeded 4 cm, and in half of them it was larger than 5 cm (max. 6.5 cm). Small
      and medium-sized tumors were removed by means of simple neurosurgical approaches.
      All of the 10 large and giant tumors were removed by a combined supra
      infratentorial presigmoid approach which enabled the approach to the whole tumor.
      Three recurrent tumors were removed subtotally, the primary surgical intervention
      removed 5 tumors radically, 4 subtotally and 1 partially. The entire removal was
      precluded due to infiltrative growth of the tumor localized in the cavernous
      sinus, firm adherence of tumor to the brain stem or to the vertebrobasillar
      vessels. Authors' own experience support the data from literature dealing with
      the relationship of unfavourable results to the size of tumor. Permanent
      impairment of cranial nerves (38.5%) occurred mostly in large and giant tumors.
      One death (7.7%) during the peri-operative period (up to one month following
      operation), as well as the second that occurred in later period succeeded the
      removal of a giant tumor. Regarding the character of the relationship of large
      clivus meningeoma to the surrounding nerve and vascular structures, the future
      improvement of functional results can be expected especially owing to early
      diagnosis. (Tab. 2, Fig. 2, Ref. 19.)

PMID- 10914465
TI  - [Resuscitation operations in patients with multiple injuries].
AB  - The authors analyze a group of 15 patients with polytrauma during a 4-year
      period. The patients had the clinical signs of severe bleeding. Despite the
      complex resuscitation care, the patients died due to consequences of haemorrhagic
      shock already during the operation or very soon after operation. All patients
      were after initial resuscitation and diagnostic procedures (apparatus breathing,
      aggressive volumotherapy, proved continuous bleeding) performed for the use of
      further resuscitation actions, namely surgical control and stoppage of bleeding,
      surgical indications. This pathophysiological consideration is reflected also in
      the title of this study. The study further discusses the modern injury conception
      of resuscitation at a operating theatre which in frame of surgical intervention
      attempts to achieve homeostasis. At the same time, the surgical approach
      frequently must prefer the methods which enable the physiological stability on
      the behalf of incomplete solution of post-traumatic anatomic integrity. The
      definite solution can be possibly performed by subsequent operation. (Ref. 5.)

PMID- 10914466
TI  - [Radiotherapy in breast carcinoma].
AB  - Radiotherapy plays an important role in the treatment of breast carcinoma. It
      becomes even more significant in the era of breast-preserving conservative
      surgical therapy. Similarly, screening and early diagnosis shift the therapy of
      breast carcinoma into the field of local therapy, which usually is a
      characteristic feature of radiotherapy. Radiotherapy is applied as primary
      treatment in primary processes or tumor bed and lymphatic drainage, as a
      secondary therapy in locoregional recurrences, and as a palliative therapy in
      metastases. It can be preoperative or postoperative--adjuvant. External
      radiotherapy is frequently combined with brachytherapy. The main aim is to
      prevent the origin of locoregional recurrences and to improve the quality of life
      and survival of patients. In the effort to use the potential of technology and
      personnel, we have introduced the isocentric half-beam technique, which makes the
      daily setting of patient more precise, reduces the risk of local recurrences and
      that of overdose in the site of the connection of irradiation fields. (Tab. 1,
      Fig. 2, Ref. 4.)

PMID- 10914467
TI  - [Fe2+-induced oxidative processes in the liver mitochondria of rats].
AB  - The study investigated the prooxidative in vitro effect of various Fe(2+)-EDTA
      concentrations on biochemical parameters of the energetic metabolism of rat liver
      mitochondria. Fe(2+)-EDTA was added in concentrations 150, 300 and 400 mmol/mg of
      mitochondrial protein. The study included the investigation of consumption of
      oxygen in state 4 (without ADP addition) and in state 3 (with ADP addition), and
      the activities of ATP-ase, superoxide dismutase (SOD) and glutathione reductase.
      The mitochondrial outer membrane dynamics were simultaneously monitored by the
      method of synchronous fluorescence fingerprint. When compared with the control
      group, the results imply that in state 4, the addition of 150 mmol of Fe2+/mg of
      mitochondrial protein caused an insignificant increase in respiration to 104%,
      whereas in state 3, the oxygen consumption was insignificantly inhibited to 82%.
      The activity of ATPase was insignificantly raised to 105%, whereas the superoxide
      dismutase activity has decreased significantly to 77%. The activity of
      glutathione reductase increased significantly to 124%. The addition of 300 mmol
      of Fe2+/mg of mitochondrial protein has caused a significant inhibition of oxygen
      consumption to 67% in state 4 and to 31% in state 3. The activity of ATPase
      showed an insignificant elevation to 104%. The activity of superoxide dismutase
      was significantly reduced to 52% and that of glutathione reductase dropped to
      72%. The addition of 400 Fe2+/mg of mitochondrial protein strongly diminished the
      oxygen consumption to 36% in state 4, and similarly to 37% in state 3. The
      activity of ATP-ase was significantly decreased to 39%, the superoxide dismutase
      activity diminished to 17% and glutathione reductase activity dropped to 37%. The
      monitoring of the mitochondrial outer membrane by the analysis of synchronous
      fluorescence fingerprint showed that the membrane is involved in these processes.
      (Fig. 5, Ref. 12.)

PMID- 10914468
TI  - [Secondary hypertrophic osteoarthropathy in a patient with pulmonary carcinoma].
AB  - BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a syndrome that manifests
      itself by clubbing of fingers, periosteal and osteal neoformation in acral bones
      and oligo- or polysynovitis. It may occur as primary form (mostly hereditary) or
      secondary form, associated with various diseases, especially neoplastic or
      infectious diseases. PURPOSE: The purpose of the study was to point out that when
      the symptoms of HOA occur, it is necessary to search for the primary disease,
      which is usually represented by tumor. METHODS: The study reports a case of a
      patient with symptoms of HOA, pulmonary adenocarcinoma confirmed by histological
      examination, and with metastases spread into peripheral lymph nodes. The
      examination of symptomatology of HOA indicated that to pulmonary carcinoma.
      RESULTS: The medical history of the patient shows that if there is, at an early
      stage, little attention paid to the fact that HOA represents a paraneoplastic
      syndrome, cancer is then confirmed later at a more advanced stage. Neglection of
      this fact delays the primary diagnosis, deteriorates the prognosis and limits the
      treatment by the extent of the cancerous process. CONCLUSION: In practice,
      manifestations of HOA may point to the primary cancerous disease. When the
      symptomatology of HOA appears, radiograms usually pick up tumours at their early
      stages, which is important for the prognosis and the strategy of their treatment.
      The situation was different with the case reported in the study, because the
      disease was diagnosed at a more advanced stage, which unfavourably affected the
      prognosis and the treatment of the disease. (Tab. 1, Fig. 4, Ref. 15.)

PMID- 10914469
TI  - [Classical electrocardiography and the Wigner distribution in the detection of
      rejection of heart transplants].
AB  - Acute cardiac allograft rejection can be detected by the SA ECG only with
      intraindividual comparison of the recordings. Standard SA ECG parameters are not
      useful in the rejection detection and until now no absolute spectral parameter
      indicating acute rejection was discovered. Frequency analysis of the QRS complex
      is characterized by changes in the frequency spectra 70-110 Hz. The Wigner-Ville
      analysis provides new possibilities for frequency analysis and markers of acute
      and chronic cardiac allograft rejection using Wigner-Ville distribution are
      intensively studied.

PMID- 10914470
TI  - [Free nerve transplants in the reconstruction of secondary defects of the
      peripheral nerves of the hand].
AB  - BACKGROUND: Peripheral nerve of the hand significantly participate ub the
      physiological functions of the hand. A defect in the area of the peripheral nerve
      therefore represents a problem, the solution of which is in the field of
      microsurgical reconstruction. The study deals with the possibility of
      microsurgical reconstruction by use of free nerve draft. SUBJECTIVE: Clinical
      observation of patients after microsurgical reconstruction of the hand peripheral
      nerve defect. MATERIAL AND METHODS: 34 patients after lesions of the median
      nerve, ulnar nerve and mutual impairment of both nerves. The evaluation according
      the known and spread system system of Medical Research Council, Seddon 1954.
      RESULTS: We have achieved very good results after isolated lesions of the median
      nerve, while the results in this, as well a in other groups are better in younger
      patients and in patients, in whom the devastation of tissue was not too great.
      Standard results were achieved in the group with isolated injury of the ulnar
      nerve and the worst results in a small group of concommitant impairment of both
      median and ulnar nerves. CONCLUSIONS: The results indicate that this method is
      unambiquously appropriate in such a complicated clinical picture. Our results are
      in accord with the data from other literature sources. MEANING FOR PRACTICE:
      Inevitability of specialized centres which would deal with this problem thus
      reducing the necessity of secondary reconstruction operations and naturally the
      reduction of financial expenditure or social support provision.

PMID- 10914471
TI  - [Ischemic disease of the lower extremity and lumbar sympathectomy].
AB  - We consider lumbar sympathectomy (LSE) to be the last attempt to improve the
      condition of the limb. Though being aware of inconsistent opinions on LSE, we are
      not opponents of this method, particularly if it is carried out in a selected
      group of patients, that is in case of: 1) treatment of frostbites, 2) treatment
      of patients at an early stage of advanced ischemia whose main symptom is moderate
      night pain at rest, 3) desiccation of chronically moist ulcerations between the
      toes, 4) treatment of patients with reflex symptomatic dystrophy (causalgia), 5)
      Buerger's disease.

PMID- 10914472
TI  - [Etiopathogenesis of age-related macular degeneration and present possibilities
      of treatment].
AB  - Age-related macular degeneration is the frequent cause of central visual acuity
      loss in the elderly patients group. The authors analyze in detail the
      pathogenesis of the process. The explanation of pathogenesis enables
      therapeutical intervention even though its possibilities are limited.
      Photodynamic therapy induces pharmacological thrombosis without any damage to the
      retina in the macular area. Pilot studies have demonstrated complete occlusion
      new vessels without any alteration of the photoreceptor layer. Age-related
      macular degeneration still remain a challenge for ophthalmologist and it also
      poses a serious social problem.

PMID- 10914473
TI  - [Changes in the retinal enzyme system in age-related macular degeneration].
AB  - The contribution interprets latest findings in retinal pathophysiology from the
      view of the retinal enzymatic system function in age related macular degeneration
      and mutual interaction between the atrophic degenerative process of the retinal
      pigmented epithelium, the Bruch's membrane and choriocapillaris at the macula.

PMID- 10914474
TI  - [Brachytherapy in the treatment of age-related macular degeneration].
AB  - Low-dose radiotherapy by local applicators--Ru106--plaques at a retinal apex dose
      of 1000-1500 cGy offers a method to treat subretinal neovascularisation by age
      related macular degeneration without destroying the overlying retina.

PMID- 10914475
TI  - [Age-related macular degeneration in fluoroangiographic findings].
AB  - Age-related macular degeneration has become the leading cause of severe visual
      loss in people over 60 years of age. The authors are reporting on characteristic
      fluorescein angiography findings obtained by fluorescein angiography of patients
      with age-related macular degeneration diagnosis.

PMID- 10914476
TI  - Leadership: it's our future.

PMID- 10914477
TI  - Introducing an evaluation of community based occupational therapy services: a
      client-centred practice.
AB  - The results of a study conducted in 1996 by the "Groupe de recherche en
      ergotherapie communautaire" (GREC), indicate that the quality of occupational
      therapy services in community settings is infrequently evaluated. A conceptual
      framework supporting such a process is presented in the context of client
      centered services with a focus on continuous health care improvement. Both the
      research process leading to the design of an assessment tool, and its congruence
      with the beliefs and values of the profession, are explored. Finally, some issues
      relating to the implementation of a formal evaluation process are discussed.

PMID- 10914478
TI  - Replication research: a purposeful occupation worth repeating.
AB  - It is common for researchers to request at the end of their published studies,
      the urgency for further studies to be completed. Unfortunately there are very few
      published studies that have replicated original studies. The purpose of this
      article is to provide a framework for understanding issues related to replication
      research that will assist occupational therapy researchers, clinicians, managers,
      students and educators to realize the importance of implementing and publishing
      replication research to establish evidence-based practice. Various areas related
      to replication research are explored. In addition, a computerized literature
      search using the search term 'replication' was completed. Only four articles
      published between 1982-1998 were discovered. This article concludes with
      recommendations to ensure replication studies are included in the occupational
      therapy literature and utilized in clinical practice.

PMID- 10914479
TI  - Accommodation needs and student-environment fit in upper secondary schools for
      students with severe physical disabilities.
AB  - The purpose of this study was to identify, from the personal perspective of
      students with disability, their needs for physical and social accommodations in
      upper secondary schools specially adapted for students with severe physical
      disabilities. The study also aimed to identify those areas of student-environment
      fit which were most often achieved. Forty-eight students in four schools in
      Sweden were assessed by occupational therapists using the School Setting
      Interview. Forty-seven students reported needs for accommodations in the school
      setting. The study indicates that schools generally were able to meet the
      students' accommodation needs in the physical environment. The schools also met
      students' accommodation needs for field trips, sport activities and assistance.
      Student-environment fit in occupations requiring reading, remembering and
      speaking was unsatisfactory. Accommodations on a general, group and individual
      level are highlighted and discussed. The study recommends that occupational
      therapists become more involved and offer society their expertise in barrier
      removal to a greater extent.

PMID- 10914480
TI  - [Validation of a measurement instrument to evaluate computer access in people
      with physical disabilities].
AB  - The aim of this study was to develop an instrument to measure performance in
      computer tasks for persons with physical impairments. The objectives were to
      assure the content validity and the internal consistency of the test as well as
      the reliability of each task. The first step was to determine the mouse and
      keyboard actions necessary to use a computer. Resulting from these actions, 15
      standardized computer tasks were designed as part of the test. To measure
      reliability and internal consistency, the test was administered twice to 19
      persons without disabilities and 17 persons with disabilities. Reliability was
      established for most of the tasks and the test showed good internal consistency.
      This instrument could contribute to the improvement of occupational therapy
      interventions regarding computer access.

PMID- 10914481
TI  - Cognitive rehabilitation: a pilot survey of therapeutic modalities used by
      Canadian occupational therapists with survivors of traumatic brain injury.
AB  - This pilot study used survey methodology to gather initial information from
      Canadian occupational therapists on 1) the delivery of cognitive rehabilitation
      services for survivors of traumatic brain injury and 2) the therapeutic
      approaches and modalities used currently to manage residual cognitive
      impairments. A questionnaire was developed, field-tested and mailed to 27 sample
      sites across Canada, selected non-randomly. Twenty returned questionnaires (74%)
      were included in the data pool. The findings revealed that a wide range of
      cognitive impairments were seen very often, with impairments in memory being most
      common. Respondents used both a cognitive remediation and compensatory approach
      and a combination of therapeutic modalities to address impairments of
      orientation, attention, and memory. There was an interesting and overlapping
      range of specific modalities identified. Inpatient and outpatient services were
      offered to survivors, primarily within the first year post-injury. These
      occupational therapists used various resources to develop expertise in cognitive
      rehabilitation. Possible implications of the pilot study findings for Canadian
      occupational therapists are high-lighted and discussed.

PMID- 10914482
TI  - Handwriting: current trends in occupational therapy practice.
AB  - The objective of this survey was to describe assessment and treatment approaches
      commonly used by occupational therapists for children exhibiting handwriting and
      related fine motor difficulties. Secondarily, the application of weights as a
      treatment modality was also explored. Fifty experienced paediatric occupational
      therapists from Ontario (46%), Quebec (22%) and six other Canadian provinces,
      were surveyed by telephone. The majority of therapists indicated that they
      evaluated gross/fine motor and perceptual skills, motor planning, quality of
      movement and sensory functioning for this population, while psychosocial and
      environmental factors were often not formally evaluated. Evaluations most
      commonly utilized included the Beery, Bruininks-Oseretsky and Gardner Tests.
      Standardized handwriting assessments were rarely employed. All used an eclectic
      treatment approach with sensorimotor most frequently selected (90%). Work setting
      and years of experience did not influence the treatment approach favoured.

PMID- 10914483
TI  - CXC chemokines in angiogenesis.
AB  - A variety of factors have been identified that regulate angiogenesis, including
      the CXC chemokine family. The CXC chemokines are a unique family of cytokines for
      their ability to behave in a disparate manner in the regulation of angiogenesis.
      CXC chemokines have four highly conserved cysteine amino acid residues, with the
      first two cysteine amino acid residues separated by one non-conserved amino acid
      residue (i.e., CXC). A second structural domain within this family determines
      their angiogenic potential. The NH2 terminus of the majority of the CXC
      chemokines contains three amino acid residues (Glu-Leu-Arg: the ELR motif), which
      precedes the first cysteine amino acid residue of the primary structure of these
      cytokines. Members that contain the ELR motif (ELR+) are potent promoters of
      angiogenesis. In contrast, members that are inducible by interferons and lack the
      ELR motif (ELR-) are potent inhibitors of angiogenesis. This difference in
      angiogenic activity may impact on the pathogenesis of a variety of disorders.

PMID- 10914484
TI  - Human neutrophil defensins selectively chemoattract naive T and immature
      dendritic cells.
AB  - Defensins, a family of cationic, structurally related, antimicrobial peptides,
      contribute to host defense by disrupting the cytoplasmic membrane of microbes.
      Here we show that human neutrophil defensins selectively induce the migration of
      human CD4+/CD45RA+ naive and CD8+, but not CD4+/CD45RO+ memory, T cells.
      Moreover, human neutrophil defensins are chemotactic for immature human dendritic
      cells derived from either CD34+ progenitors or peripheral blood monocytes. Upon
      maturation induced by treatment with tumor necrosis factor alpha (TNF-alpha),
      dendritic cells lose their responsiveness to human neutrophil defensins. The
      chemotactic effect of human neutrophil defensins on both T and dendritic cells is
      pertussis toxin-sensitive, suggesting that a G(ialpha) protein-coupled receptor
      is responsible. Human neutrophil defensins are also chemotactic for immature
      murine dendritic cells. These data suggest that, in addition to their
      antimicrobial role, human neutrophil defensins also contribute to adaptive
      immunity by mobilizing T cells and dendritic cells.

PMID- 10914486
TI  - Age-associated increase of basal corticosterone levels decreases ED2high, NF
      kappaBhigh activated macrophages.
AB  - The proportion of cells with a high density of ED2 (ED2high cells) in peritoneal
      cells from old rats was significantly lower than that from young rats. The
      expression of major histocompatibility complex class II (MHC class II) molecules,
      the antigen presentation, production of interleukin (IL)-1beta and IL-6, and
      nuclear factor-kappaB activity in ED2high cells were markedly higher than those
      in cells with a low density of ED2 (ED2low cells), although no significant
      difference was observed in the expression of MHC class II molecules and the
      antigen presentation between ED2high cells from young and old rats. Meanwhile,
      basal corticosterone concentration in serum and glucocorticoid (GC) receptor mRNA
      expression in peritoneal cells increased significantly in old rats. The
      proportion of ED2high cells was increased by adrenalectomy in young rats.
      Furthermore, nuclear translocation of GC receptor was observed in ED2low cells,
      whereas GC receptor was detected in cytoplasmic extracts from ED2high cells.
      These results suggest that the decrease in functional ED2high macrophages with
      age results in the age-associated decline of immune responses, which is
      regulated, in part, by the basal GC concentration.

PMID- 10914485
TI  - Altered caspase expression results in delayed neutrophil apoptosis in acute
      pancreatitis.
AB  - Acute pancreatitis (AP) may lead to the development of multiple organ dysfunction
      syndrome (MODS), especially in severe cases. Resolution of such inflammatory
      responses is dependent on neutrophil apoptosis. Delays in this apoptotic response
      are associated with persistent inflammation and subsequent tissue damage. The aim
      of this study is to determine the effects of AP on neutrophil apoptosis and to
      investigate the underlying mechanisms involved. Neutrophils and serum were
      isolated from control (n=10) and from patients with AP (mild, n=35, and severe,
      n=5). Neutrophil apoptosis was assessed by propidium iodide DNA staining using
      flow cytometry. Caspase, glutathione-S-transferase (GST), and Mcl-1 protein
      expression were assessed by SDS-PAGE western blotting. Serum interleukin (IL)
      1beta and granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were
      measured by ELISA. Neutrophils isolated from patients with AP show a significant
      delay in spontaneous neutrophil apoptosis. Serum factors contributed to this
      delay with increases in IL-1beta and GM-CSF. Isolated neutrophils were resistant
      to Fas antibody-induced apoptosis. Caspases represent a central mechanism for
      spontaneous and Fas antibody-induced neutrophil apoptosis. Procaspase 3
      expression was decreased in mild and severe cases, but this effect was
      independent of serum factors. Increases in GST expression may also contribute to
      the antiapoptotic effect. Altered caspase expression may represent an additional
      factor contributing to delayed neutrophil apoptosis. This may contribute to the
      development of AP and its related complications.

PMID- 10914488
TI  - Adhesion of human lung mast cells to bronchial epithelium: evidence for a novel
      carbohydrate-mediated mechanism.
AB  - Mast cells contribute to the pathophysiology of asthma through their
      immunomediator-secretory activity in response to both immunological and
      nonimmunological stimuli, and infiltrate the bronchial epithelium in this
      disease. We hypothesized that human lung mast cells (HLMC) localize to the
      bronchial epithelium via a specific cell-cell adhesion mechanism. We investigated
      the adhesion of HLMC to primary bronchial epithelial cells and the bronchial
      epithelial cell line BEAS-2B. HLMC adhered avidly to both primary cultures of
      bronchial epithelial cells and BEAS-2B cells (mean adhesion 68.4 and 60.1%,
      respectively) compared with eosinophil adhesion to BEAS-2B (mean adhesion 10.3%).
      HLMC adhesion did not alter after epithelial activation with cytokines, did not
      require Ca2+, and was not integrin-mediated. IgE-dependent activation of HLMC
      produced an approximately 40% inhibition of adhesion. There was significant
      attenuation of adhesion after incubation of HLMC with pronase, beta
      galactosidase, and endo-alpha-N-acetylgalactosaminidase, indicating that HLMC
      adhere to bronchial epithelial cells via galactose-bearing carbohydrates
      expressed on a cell-surface peptide(s).

PMID- 10914487
TI  - Expression on human eosinophils of CD148: a membrane tyrosine phosphatase.
      Implications in the effector function of eosinophils.
AB  - The role of protein tyrosine phosphatases (PTP) is crucial in regulating the
      phosphorylation status of cells. CD148 is a recently described membrane-type PTP.
      In this study, we have demonstrated that this molecule is expressed on human
      eosinophils and eosinophilic cell line EoL-3. Interestingly, our data also showed
      that this molecule acts as a transduction molecule on these cells. Thus, the
      crosslinking of CD148 was able to induce the degranulation and the induction of
      superoxide anion generation. By using specific inhibitor and by western blotting,
      we have shown that tyrosine kinase activation is involved in this transduction
      pathway. In addition, we have shown the presence of a serine/threonine kinase
      activity associated with CD148. In conclusion, the activation capacity of CD148
      on eosinophils suggests a potential role of this molecule on inflammatory
      diseases, such as allergic and parasitic diseases, associated with eosinophilia.

PMID- 10914489
TI  - Preferential sites for stationary adhesion of neutrophils to cytokine-stimulated
      HUVEC under flow conditions.
AB  - Neutrophils form CD18-dependent adhesions to endothelial cells at sites of
      inflammation. This phenomenon was investigated under conditions of flow in vitro
      using isolated human neutrophils and monolayers of HUVEC. The efficiency of
      conversion of neutrophil rolling to stable adhesion in this model was >95%.
      Neither anti-CD11a nor anti-CD11b antibodies significantly altered the extent of
      this conversion, but a combination of both antibodies inhibited the arrest of
      rolling neutrophils by >95%. The efficiency of transendothelial migration of
      arrested neutrophils was >90%, and the site of transmigration was typically <6
      microm from the site of stationary adhesion. Approximately 70% of transmigrating
      neutrophils migrated at tricellular corners between three adjacent endothelial
      cells. A model of neutrophils randomly distributed on endothelium predicted a
      significantly greater migration distance to these preferred sites of
      transmigration, but a model of neutrophils adhering to endothelial borders is
      consistent with observed distances. It appears that stable adhesions form very
      near tricellular corners.

PMID- 10914490
TI  - Monitoring of neutrophil priming in whole blood by antibodies isolated from a
      synthetic phage antibody library.
AB  - Neutrophil activation is a multistep process. In vitro activation of neutrophils
      with semiphysiological activators is optimal only after preactivation or priming
      with cytokines, chemotaxins, and/or bacterial products. Until now, no antibodies
      have been developed that can distinguish between resting and (cytokine) primed
      neutrophils with a sufficient dynamic range necessary for screening clinical
      samples. We have isolated two human phage antibodies, designated MoPhab A17 and
      A27, from a synthetic bacteriophage antibody library. These phage antibodies
      recognize epitopes that are upregulated on neutrophils present in whole blood
      treated with low priming concentrations of cytokines, such as GM-CSF and TNF
      alpha. This induction was time- and concentration-dependent and optimal at
      concentrations that are sufficient for priming functional responses in
      neutrophils: GM-CSF (10 pM) and TNF-alpha (100 IU/ml). PMNs, isolated from the
      peripheral blood of chronic obstructive pulmonary disease (COPD) patients with a
      clinical exacerbation, exhibited a partial in vivo primed phenotype. These
      antibodies promise to be an ideal tool to monitor disease activity in whole blood
      of patients with inflammatory diseases.

PMID- 10914491
TI  - Sulfatide binding and activation of leukocytes through an L-selectin-independent
      pathway.
AB  - Sulfatide has been reported to activate leukocytes through L-selectin. Here we
      provide evidence that sulfatide binds to and activates leukocytes through both L
      selectin-dependent and -independent pathways. Rat leukocytes of various sources
      shed surface L-selectin after phorbol myristate acetate (PMA) treatment, however,
      these cells retained the ability to bind sulfatide. In addition, sulfatide also
      bound to an L-selectin-negative cell line EL-4, and the binding was up-regulated
      by PMA. Sulfatide induced aggregation of L-selectin-positive lymphocytes, which
      was highly dependent on divalent cations, protein tyrosine kinases (PTK), and
      protein kinase C (PKC), but was independent of beta1 and beta2 integrins. In
      contrast, sulfatide-induced EL-4 cell aggregation required an LFA-1/ICAM-1
      adhesion pathway but not PTK and PKC. A sulfatide receptor of 65 kDa was isolated
      from EL-4 cells. Taken together, this study suggests that sulfatide can bind to
      and activate leukocytes through an L-selectin-independent molecule and triggers
      signal transduction pathways different from those induced by L-selectin
      activation.

PMID- 10914492
TI  - LFA-1 (CD11a/CD18) triggers hydrogen peroxide production by canine neutrophils.
AB  - The respiratory burst of neutrophils stimulated by chemotactic factors is
      markedly augmented by Mac-1-dependent adhesion such as the interaction of Mac-1
      (CD11b/CD18) with intercellular adhesion molecule-1 (ICAM-1; CD54) expressed on
      the surface of parenchymal cells (e.g., cardiac myocytes). In the current study,
      we evaluate the hypothesis that lymphocyte function-associated antigen-1 (LFA-1;
      CD11a/CD18) can also trigger the respiratory burst in neutrophils. To isolate LFA
      1/ICAM-1 interactions from Mac-1/ ICAM-1 interactions, full-length chimeric ICAM
      1 was developed and expressed in L cells with domains 1 and 2 from canine ICAM-1
      and domains 3-5 from human ICAM-1 (C1,2;H3-5). We have shown that canine
      neutrophils do not bind to human ICAM-1. We demonstrated that chimeric ICAM-1
      C1,2;H3-5 supported only LFA-1-dependent adhesion of canine neutrophils and that
      such adhesion triggered rapid onset of H2O2 production from canine neutrophils.
      The following seven experimental conditions distinguished LFA-1-dependent H2O2
      production from Mac-1-dependent production: It did not require exogenous
      chemotactic stimulation; H2O2 release was more rapid, but the amount released was
      <40% of that mediated by Mac-1 adhesion; it was inhibited by anti-CD11a and anti
      ICAM-1 antibodies; in contrast to that mediated by Mac-1, it was not inhibited by
      anti-CD11b antibody, neutrophil inhibitory factor (NIF), or cytochalasin B or H7.
      Thus, canine neutrophils seem to be able to utilize two members of the beta2
      integrin family to interact with ICAM-1 and signal H2O2 production, with LFA-1 at
      an early stage without prior chemotactic stimulation and Mac-1 at a later stage
      requiring chemotactic stimulation.

PMID- 10914493
TI  - T cell lysis of murine renal cancer: multiple signaling pathways for cell death
      via Fas.
AB  - Activated T cells lyse the murine renal cancer Renca. We have examined the
      mechanism of tumor cell lysis with the use of T cells derived from C57BL/6,
      BALB/c, B6.gld, and B6.Pfp-/- mice. C57BL/6 and BALB/c T cells can lyse Renca
      cells through the use of both granule- and Fas ligand (FasL)-mediated pathways.
      However, B6.gld T cells predominantly use granule-mediated killing, whereas
      B6.Pfp-/- T cells use FasL. The lysis of Renca by Pfp-/- T cells is only
      partially inhibited by the caspase inhibitor ZVAD-FMK, suggesting that caspase
      independent signaling is also important for Renca cell lysis. When the reactive
      oxygen scavenger butylated hydroxyanisole was used alone or in combination with
      ZVAD-FMK a substantial reduction of Renca lysis was observed. Therefore, the
      caspase-independent generation of reactive oxygen intermediates in Renca after
      Fas triggering contributes to the lysis of these cells.

PMID- 10914494
TI  - Oxidative stress as a necessary factor in room temperature-induced apoptosis of
      HL-60 cells.
AB  - HL-60 cells undergo apoptosis when placed at room temperature (RT) [Shimura et
      al. (1997) FEBS Lett. 417, 379-384]. We report that superoxide anion radical, one
      of the reactive oxygen species (ROS), was produced after RT treatment. Affinity
      blot analysis with a biotinylated YVAD-CHO detected the generation of processed
      peptides with molecular masses of 15-25 kDa. Activation of such an ICE-like
      protease was completely abolished by N-acetylcysteine and exogenously expressed
      Bcl-2, known as antioxidants. We concluded that oxidative stress was a critical
      factor in the signal cascade of the apoptosis. Western blot analysis and
      experiments using tetrapeptide inhibitors suggested that caspases-1, -3, -4, -6,
      and -9 did not have an essential role in the apoptotic cascade. It is interesting
      that cyclosporin A (CsA) blocked RT-induced apoptosis with an inhibition of
      cytochrome c release from mitochondria. CsA, however, generated a significant
      amount of ROS with considerable reduction of mitochondrial membrane potential,
      implying that oxidative stress was one necessary factor for RT-induced apoptosis.
      It is also likely that mitochondrial membrane potential and the release of
      apoptotic factors from cytoplasm are differently regulated. Taken together with
      the reports that some Burkitt lymphoma cells showed apoptosis when exposed at low
      temperature followed by rewarming, and that hepatocytes or liver endothelial
      cells are susceptible to cold-induced apoptosis through the ROS function, we
      propose that studying the mechanism of RT-induced apoptosis of HL-60 cells may
      provide a therapeutic strategy for pathological conditions involving ROS, such as
      neurodegenerative diseases and ischemia.

PMID- 10914495
TI  - Suppression of TNF-alpha production in human mononuclear cells by an adenosine
      kinase inhibitor.
AB  - Adenosine exerts potent anti-inflammatory activities through inhibition of
      cytokine synthesis by activated monocytes. Adenosine is rapidly phosphorylated
      intracellularly by adenosine kinase. GP515, an adenosine kinase inhibitor,
      prevents the phosphorylation of adenosine to AMP and thereby locally enhances the
      adenosine concentration. GP515 has exhibited significant anti-inflammatory
      effects in several murine models of inflammation. In this study we investigated
      the effect of GP515 alone and in combination with exogenous adenosine or with
      rolipram, a phosphodiesterase inhibitor, on tumor necrosis factor alpha (TNF
      alpha) synthesis in human peripheral blood mononuclear cells (PBMC) or whole
      blood. Lipopolysaccharide (LPS; 10 ng/mL)-stimulated PBMC were incubated in the
      absence or presence of these substances. GP515 alone showed a dose-dependent
      suppression of TNF-alpha production with an IC50 of 80 microM. The TNF-alpha
      inhibiting effects of adenosine and GP515 were reversed in the presence of the
      cAMP antagonist (Rp)-cAMPS, supporting the hypothesis of a cAMP-mediated pathway.
      Combinations of GP515 with either adenosine or rolipram led to an additive
      inhibition of TNF-alpha synthesis. These experiments are the first to demonstrate
      efficacy of an adenosine kinase inhibitor in TNF-alpha suppression in cells of
      human origin. The findings form a basis to investigate these strategies in animal
      models of TNF-alpha-mediated chronic inflammatory diseases.

PMID- 10914497
TI  - Vascular endothelial cells provide T cells with costimulatory signals via the
      OX40/gp34 system.
AB  - We investigated whether gp34, the ligand of OX40, expressed on EC is involved in
      costimulation of T cells. Normal CD4+ T cells were stimulated with anti-CD3
      coated beads, phytohemagglutinin (PHA), or concanavalin A (Con A) in the presence
      or absence of irradiated human umbilical vein endothelial cells (HUVEC).
      Stimulation of T cells with each of these mitogens results in significant T-cell
      proliferation only when HUVEC were present, and this proliferation was inhibited
      markedly by anti-OX40 or anti-gp34 monoclonal antibody (mAb). T cells cultured
      with HUVEC produced more interleukin (IL)-2 than those cultured without HUVEC.
      The addition of anti-IL-2R alpha chain and anti-IL-2R beta chain mAbs abolished
      the costimulatory effects of HUVEC. Thus, the augmentation of T-cell
      proliferation appears to be attributable to increased IL-2 production. These
      results suggest that gp34 expressed on HUVEC plays a role in potentiation of T
      cell immune response by providing OX40+ T cells with costimulatory signals.

PMID- 10914496
TI  - Ligand activation of nerve growth factor receptor TrkA protects monocytes from
      apoptosis.
AB  - Nerve growth factor (NGF) receptors are expressed in different cell types outside
      the nervous system, and increasing evidence indicates that NGF can act as a
      regulatory molecule during inflammatory and immune responses. In this study, we
      show that triggering of the high-affinity NGF receptor TrkA with agonists
      protects monocytes from apoptosis induced by gliotoxin or UVB radiation. TrkA
      stimulation up-regulates the expression of the anti-apoptotic Bcl-2 family
      members, Bcl-2, Bcl-XL, and Bfl-1. On the other hand, TrkA stimulation does not
      change the expression of MHC, CD80, CD86, CD40, and CD54 molecules, nor the
      antigen-presenting function of monocytes. In addition, during in vitro monocyte
      to dendritic cell differentiation TrkA expression is progressively lost,
      suggesting that NGF selectively affects monocyte but not dendritic cell survival.

PMID- 10914498
TI  - The effects of NO synthase inhibitors on murine collagen-induced arthritis do not
      support a role of NO in the protective effect of IFN-gamma.
AB  - DBA/1 mice deficient in expressing the interferon-gamma (IFN-gamma) membrane
      receptor (IFN-gammaR KO mice) are more susceptible to collagen-induced arthritis
      (CIA) than wild-type mice, indicating that endogenous IFN-gamma plays a
      protective role in the pathogenesis of CIA. In IFN-gammaR KO mice, nitric oxide
      (NO) production during CIA is impaired. Because NO is known to exert
      immunosuppressive and anti-inflammatory effects in certain model systems, the
      protective effect of IFN-gamma might be mediated by NO. Here, we tested in wild
      type mice whether inhibition of NO production by metabolic inhibitors,
      aminoguanidine (AG) and L-N-(1-iminoethyl)lysine (L-NIL), could mimic the
      ablation of the IFN-gamma receptor. A high-dose regimen of AG supplied in the
      drinking water inhibited NO production, disease development, and anticollagen
      antibody production but was also associated with transient body weight loss. At a
      dose and time regimen that still inhibited NO production but did not cause body
      weight loss, AG failed to affect disease scores. Treatment with L-NIL, which more
      specifically than AG affects inducible NO production, caused a slight increase in
      anticollagen antibody production although not significantly affecting disease
      occurrence. These data indicate that the diminished capacity of the IFN-gammaR KO
      mice to produce NO following immunization with collagen is unlikely to account
      for their higher susceptibility to CIA.

PMID- 10914499
TI  - IL-4 production by human polymorphonuclear neutrophils.
AB  - Polymorphonuclear neutrophils (PMN) are phagocytic cells, able to secrete a large
      range of cytokines, including inflammatory cytokines, chemokines, as well as the
      Th1 cytokines interferon-gamma (IFN-gamma) and interleukin (IL)-12. Although PMN
      do not seem to express IL-10 and IL-13, no information exists on the ability of
      PMN to produce IL-4. Therefore intracellular flow cytometry was performed in the
      presence or absence of Brefeldin A. Similarly to eosinophils, freshly isolated
      neutrophils from normal donors contained low amounts of IL-4, which significantly
      increased upon culture with Brefeldin A (P < 0001). Immunostaining performed on
      cytospin preparations of normal granulocytes confirmed the presence of
      intracellular IL-4. Using a highly sensitive ELISA, the levels of IL-4 secreted
      by cultured PMN and peripheral blood mononuclear cells (PBMC) were compared. PBMC
      secrete up to 60 times more IL-4 as PMN but, in the presence of calcium
      ionophore, only PMN showed a slight but significant increase in IL-4 secretion (P
      < 0.05). In conclusion, we report here the presence within human PMN of
      intracellular IL-4, which can at least partly be released under calcium ionophore
      stimulation. The relevance of this production of IL-4 by human PMN is discussed.

PMID- 10914500
TI  - Proteasome-mediated regulation of interleukin-1beta turnover and export in human
      monocytes.
AB  - Interleukin-1beta is a secreted protein that accumulates in the cytosol as an
      inactive precursor (pIL-1beta) before processing and release of biologically
      active protein. To understand the impact of this property on IL-1beta production,
      we examined the intracellular stability of pIL-1beta in lipopolysaccharide (LPS)
      stimulated human monocytes. Precursor IL-1beta was degraded with a relatively
      short half-life of 2.5 h in the promonocytic cell line, THP-1, and in primary
      monocytes. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal) stabilized pIL-1beta
      levels in THP-1 cells, suggesting that degradation was proteasome-mediated, but
      this inhibitor was toxic for primary monocytes, causing release of pIL-1beta as
      well as the cytoplasmic enzyme, lactate dehydrogenase (LDH) into supernatants. In
      contrast, clasto-lactacystin beta-lactone, a specific inhibitor of the
      proteasome, caused a dose-dependent stabilization of intracellular pIL-1beta, and
      this led to a corresponding increase in mIL-1beta and pIL-1beta but not LDH
      release into culture supernatants. Therefore, by regulating intracellular levels
      of precursor IL-1beta, the proteasome plays an important and previously
      unrecognized role in controlling the amount of biologically active IL-1beta that
      is exported by activated monocytes.

PMID- 10914501
TI  - Thrombopoietin enhances neutrophil production by bone marrow hematopoietic
      progenitors with the aid of stem cell factor in congenital neutropenia.
AB  - We examined the effects of granulocyte colony-stimulating factor (G-CSF), stem
      cell factor (SCF), and thrombopoietin (TPO), alone or in combination, on the
      generation of neutrophils by bone marrow (BM) cells from three patients with
      severe congenital neutropenia (SCN) through the use of a serum-deprived liquid
      culture system. Synergistic effects of G-CSF and SCF on the neutrophil production
      by BM CD34+CD38+c-kit+ cells were observed in SCN patients as well as in normal
      controls. The addition of TPO to the culture containing G-CSF and SCF further
      augmented the growth of neutrophils in the two groups. Single-cell culture
      experiments revealed that the three-factor combination caused increases in both
      the number and size of neutrophil colonies compared with G-CSF + SCF in normal BM
      cells, whereas only a significant increment in the colony size was observed in
      SCN patients. Even in the presence of SCF or SCF + TPO, the concentrations of G
      CSF necessary for the substantial production of neutrophils by CD34+CD38+c-kit+
      cells were higher in two patients compared with the levels obtained by normal
      control cells. In addition, TPO did not accelerate the maturation of neutrophilic
      cells supported by G-CSF + SCF. When BM CD34+CD38-c-kit+ cells were targeted, the
      addition of TPO to the culture containing G-CSF and SCF was required for
      significant neutrophil colony growth in the two groups. These results suggest
      that TPO enhances the G-CSF-dependent neutrophil production with the aid of SCF
      in this disorder.

PMID- 10914502
TI  - The colony-stimulating factors and collagen-induced arthritis: exacerbation of
      disease by M-CSF and G-CSF and requirement for endogenous M-CSF.
AB  - There is increasing evidence that the colony-stimulating factors (CSFs) may play
      a part in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis
      (RA). We examined the involvement of macrophage CSF (M-CSF or CSF-1) and
      granulocyte CSF (G-CSF) in collagen-induced arthritis (CIA), a murine model of
      RA. Daily injections of M-CSF or G-CSF, 20-24 days postprimary immunization with
      type II collagen, exacerbated disease symptoms in suboptimally immunized DBA/1
      mice. Support for the involvement of endogenous M-CSF in CIA was obtained by
      studies in which neutralizing monoclonal antibody reduced the severity of
      established CIA and also by studies showing the resistance of M-CSF-deficient
      op/op mice to CIA induction. These studies show that M-CSF and G-CSF can be
      proinflammatory in CIA and provide evidence that macrophage- and granulocyte
      lineage cells can exacerbate CIA. Our results also show that M-CSF-dependent
      cells are essential for CIA development, suggesting M-CSF may be a suitable
      target for therapeutic intervention in RA.

PMID- 10914503
TI  - Gene profiling approach in the analysis of lymphotoxin and TNF deficiencies.
AB  - Mice with combined lymphotoxin-alpha (LTalpha) and tumor necrosis factor (TNF)
      deficiencies show defects in the structure of peripheral lymphoid organs such as
      spleen, lymph nodes, and gut-associated lymphoid tissues. To identify genes
      associated with this defective phenotype in spleen, we applied a gene profiling
      approach, including subtractive cloning and gene array hybridizations, to mice
      with combined TNF/LT deficiency. The differentially expressed genes identified by
      these techniques was then evaluated by Northern blot analysis for splenic
      expression in knockout mice with single LTalpha or single TNF deficiency. Most of
      the genes detected in this analysis are directly or indirectly associated with
      disrupted LT and not TNF signaling.

PMID- 10914504
TI  - The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes
      apoptosis.
AB  - The regulation of polymorphonuclear leukocyte (PMN) apoptosis can influence the
      duration of the inflammatory response. We have previously shown that PMN
      apoptosis is delayed by matrix adhesion and hypoxia; however, the mechanisms
      responsible for this delay are not well understood. Mcl-1, an antiapoptotic Bcl-2
      family member, is present in neutrophils; therefore, we sought to characterize
      its localization and function as it relates to PMN apoptosis. We found that Mcl-1
      localized to the nucleus and cytoplasm and that expression levels decreased as
      PMN were aged in culture. Reducing available Mcl-1 through the use of antisense
      oligonucleotides demonstrated that Mcl-1 is necessary to delay apoptosis during
      normal PMN aging and hypoxia but is not required for suppression of apoptosis by
      laminin adhesion. Our results demonstrate a distinct expression pattern of Mcl-1
      and that Mcl-1 is crucial for the delay of apoptosis initiated by certain
      antiapoptotic factors.

PMID- 10914505
TI  - A change of course for tertiary education.

PMID- 10914506
TI  - Pregnancies among New Zealand teenagers: trends, current status and international
      comparisons.
AB  - AIMS: To examine trends in birth and total pregnancy rates among teenage women in
      New Zealand, ethnic differences and international comparisons. METHODS: Routinely
      collected data on births and abortions by age in New Zealand have been used to
      derive teenage birth rates and estimated total teenage pregnancy rates. RESULTS:
      The teenage birth rate rose from the end of the Second World War until 1972, then
      dropped until 1986, since when it has risen slightly. An increase in the
      proportion of teenage pregnancies aborted since 1986 has prevented a more marked
      increase in the birth rate. In 1997, the teenage birth rate for Maori was nearly
      five times, and the Pacific rate over three times, that of European/Pakeha
      teenagers. Although the abortion rate was slightly higher among Maori than
      European/Pakeha teenagers, Maori who became pregnant were much less likely to
      have an abortion. Of the developed OECD countries, only the USA has a higher
      teenage birth rate than New Zealand. However, the teenage birth rate among
      European/Pakeha in New Zealand, while higher than in many Western European
      countries, is similar to the total rate in Australia, and less than that in the
      UK and Canada. CONCLUSIONS: This analysis shows that using routinely collected
      data, it is possible to monitor national teenage pregnancy rates. Improvements in
      monitoring could be made by collecting ethnicity data on abortions and births in
      a consistent manner, together with the area of residence of women having
      abortions. The findings indicate the importance of understanding the impact on
      Maori women who become pregnant as teenagers and on their children.

PMID- 10914507
TI  - Domestic fire injuries treated in New Zealand hospitals 1988-1995.
AB  - AIM: To describe demographic features of people discharged from New Zealand
      hospitals following injury caused by fire and flame in domestic locations.
      METHOD: Review of hospital discharge data for the years 1988-1995. RESULTS: From
      1988-1995 there were 1493 discharges from New Zealand hospitals with injury as
      the result of fire and flame in domestic locations. Age-standardised
      hospitalisation rates for fire related injury over the period have been stable,
      with an overall discharge rate of 5.45 hospitalisations per 100000 person years.
      Male discharges exceeded female in all years (RR 1.97, 95% CI 1.73-2.14).
      Stratification by age indicated that discharge rates were highest among New
      Zealanders aged over 75 years and under fifteen years. Maori discharge rates
      exceeded non-Maori over all age groups (RR 3.3, 95% CI 2.82-3.58). CONCLUSION:
      Maori discharge rates for fire related injury in the home are substantially
      higher than non-Maori in all age groups, and highlight the importance of
      developing culturally appropriate injury prevention strategies. Social and
      material determinants of injury need to be addressed through public policy,
      provision of quality housing and community development initiatives.

PMID- 10914508
TI  - Psychiatric casualties of World War II.
AB  - AIMS: To observe the natural history of traumatised war veterans. METHODS: A
      clinical audit of 147 World War II psychiatric war pensioners. RESULTS: Of these
      veterans only 37% have a clinically sustainable DSM diagnosis of chronic post
      traumatic stress disorder (PTSD). Trauma-related and somatic symptoms of severity
      attributable to active war service, were volunteered by 48%. These symptoms were
      insufficient to fulfil DSM diagnosis criteria for PTSD. CONCLUSIONS: PTSD is a
      robust clinical entity, yet many victims of trauma appear to suffer chronic sub
      syndromal PTSD. The clinical spectrum of trauma response is more variable than is
      currently diagnostically acceptable by DSM criteria.

PMID- 10914510
TI  - The New Zealand National Kidney Allocation System. Renal Transplant Sub
      committee.

PMID- 10914509
TI  - Blood chemistry profile of a South Pacific Island population.
AB  - AIMS: To determine basic blood chemistry parameters in the population of the
      island of Mauke in the South Pacific. METHODS: As a part of a health survey
      carried out in 1992, 24 laboratory parameters were measured in serum samples of
      502 subjects representing 80.8% of the total population. RESULTS: Blood glucose,
      uric acid and globulin values were above the respective reference intervals in
      9%, 5% and 4% of the subjects. Blood urea nitrogen and serum creatinine values
      were elevated in 1.8% and 1.2% of the subjects. Hypoalbuminaemia was found in
      1.2% to 4% of the subjects, more frequently in the older age groups. Gamma
      glutamyltransferase levels were elevated in 6.2% of the subjects. Iron values
      were below the reference interval in 8.0% of the subjects. Serum cholesterol
      levels were elevated in 4.4% of the subjects. CONCLUSIONS: The blood chemistry
      data reflect the disease profile of this Pacific Island population including the
      presence of diabetes and iron deficiency as well as renal, hepatic and infectious
      diseases. The data can be used in comparative inter-island studies as well as in
      those between Pacific Island and other populations.

PMID- 10914511
TI  - Iron and performance--important for all New Zealanders?

PMID- 10914512
TI  - Vitamin D deficiency and rheumatoid arthritis.

PMID- 10914513
TI  - ACC and back injuries.

PMID- 10914514
TI  - Carotid endarterectomy in New Zealand.

PMID- 10914515
TI  - Doctors as managers.

PMID- 10914516
TI  - Research in general practice or general practice research.

PMID- 10914517
TI  - Meningococcus-not just meningitis.

PMID- 10914518
TI  - ACC elective surgery contracts.

PMID- 10914519
TI  - Salaried general practitioners?

PMID- 10914520
TI  - Avoiding the fraud and abuse pitfalls.
AB  - In the current medical environment, long-standing and appropriate referral
      patterns among medical care providers may be scrutinized for possible violation
      of a technical provision of Medicare, the "anti-fraud and abuse statute." The
      physician can avoid misunderstanding by preparing and implementing a compliance
      program.

PMID- 10914521
TI  - Electronic monitoring of treatment compliance in patching for amblyopia.

PMID- 10914522
TI  - Landmarks in the evolution of cataract surgery.

PMID- 10914523
TI  - Susruta's role in the development of cataract surgery.

PMID- 10914524
TI  - Sir Harold Ridley receives England's highest honor.

PMID- 10914525
TI  - The buccal mucosal bleeding time.

PMID- 10914526
TI  - Kidney transplantation in dogs with naturally occurring end-stage renal disease.
AB  - Renal allografts were performed between unrelated donors and 15 dogs with
      naturally occurring end-stage renal disease. Donor selection was based on
      compatible dog erythrocyte antigen typing and cross-matching. An
      immunosuppressive protocol consisting of rabbit antidog antithymocyte serum,
      cyclosporin-A, azathioprine, and prednisone was used to control postoperative
      rejection of the donated kidney. Although seven animals died because of technical
      failures or rejection episodes, a median survival time of eight months has been
      achieved, with two dogs living for longer than five years after surgery. Long
      term survivors have died from a variety of problems not related to renal
      allograft rejection.

PMID- 10914527
TI  - Successful treatment of intratracheal cuterebrosis in two cats.
AB  - Two cases of feline intratracheal myiasis due to Cuterebra spp. larvae are
      reported. Both cats presented with inspiratory dyspnea and a nonproductive cough.
      One larva was successfully removed during thoracotomy, and the other was removed
      during bronchoscopy using forceps passed through a bronchoscope operating
      channel. Clinical signs were alleviated following removal of the larvae.

PMID- 10914528
TI  - Esophageal motility dysfunction in cats: a study of 44 cases.
AB  - A retrospective study evaluated cases of feline esophageal dysfunction. Cats
      identified had contrast esophagrams performed during a six-year period. Of 56
      cases undergoing esophagography, 51 had complete records available for review.
      Forty-four cases were felt to be abnormal and were included in the study. Cases
      were analyzed for signalment, presenting complaints, and identifiable causes of
      abnormal esophageal motility. Response to treatment and case outcome were also
      reviewed. The signalment of the cases varied widely, especially in age. The
      occurrence of esophageal motility dysfunction was low, comprising only 0.05% of
      all feline cases seen in a six-year period. Forty-three percent of cases were
      considered idiopathic, and 57% were congenital or diagnosed with conditions known
      to cause esophageal motility dysfunction. The causative disease states included
      myasthenia gravis, mediastinal masses, vascular ring anomalies, dysautonomia, and
      esophageal stricture. Seventy-eight percent of those treated with medical therapy
      (i.e., combinations of sucralfate, H2 receptor antagonists, and either
      metoclopramide or cisapride) showed clinical improvement.

PMID- 10914529
TI  - Tracheal collapse in a young boxer.
AB  - A four-month-old, female boxer developed severe inspiratory dyspnea three days
      after elective ear crop surgery. Radiographs confirmed the diagnosis of collapse
      of the distal cervical trachea. The puppy was treated with oxygen, aminophylline,
      and ampicillin, but required emergency tracheostomy to stent the collapsed
      region. Clinical signs resolved following application of five polypropylene total
      ring prostheses, and the puppy continued to do well despite significant growth to
      maturity.

PMID- 10914531
TI  - Testosterone-producing thecoma in a female cat.
AB  - Virilizing features in a six-year-old, spayed female, domestic shorthair cat
      resolved following surgical removal of a mass at the left ovarian stump. Serum
      testosterone concentration before surgery was elevated. Clinical signs resolved
      and testosterone concentration normalized after removal of the tumor. A
      testosterone-producing thecoma was found on histopathology. This report presents
      the case report and literature review of thecomas.

PMID- 10914530
TI  - Phenol poisoning in three dogs.
AB  - Three adult dogs were evaluated following oral administration of phenol by the
      owner. All three dogs experienced severe oral and gastric ulceration.
      Hematological abnormalities included neutropenia with the presence of toxic
      neutrophils, thrombocytopenia, and increased muscle enzymes. Endoscopic
      examination was performed, and biopsies yielded a diagnosis of gastric mucosal
      necrosis in two of the dogs. Following supportive care, the dogs recovered
      completely. Phenol is a caustic, highly poisonous derivative of coal tar. The
      dogs of this report were poisoned inadvertently by their owner who received
      misinformation concerning the use of this chemical via the Internet.

PMID- 10914532
TI  - Primary osteosarcoma of the synovium in a dog.
AB  - An eight-year-old, spayed female Labrador retriever was presented for evaluation
      of left thoracic limb lameness. Radiographs of the left elbow revealed
      mineralization of the soft tissues surrounding the joint, with no evidence of
      periarticular bony lysis. Biopsy of the synovial tissues of the left radiohumeral
      joint yielded a diagnosis of osteosarcoma (OSA). The dog was treated with
      palliative radiotherapy, piroxicam, and carboplatin chemotherapy, which resulted
      in excellent pain control for approximately eight months. Amputation of the
      affected limb was then performed. Six months later, the dog developed multiple
      subcutaneous OSA metastases, and the dog was euthanized 15 months after diagnosis
      due to refractory vomiting. This report documents the first known case of primary
      OSA of the synovium in any species.

PMID- 10914533
TI  - Extraskeletal osteosarcoma in the duodenum of a cat.
AB  - A three-year-old, male neutered domestic longhair cat was referred for evaluation
      of icterus, vomiting, and anorexia. Abdominal ultrasonography revealed a proximal
      duodenal mass obstructing the common bile duct. The mass was surgically resected,
      and a cholecystoduodenostomy was performed. The histopathological diagnosis was
      osteosarcoma. Thoracic radiographs showed no evidence of metastasis, and bone
      scintigraphy revealed no signs of a primary skeletal osteosarcoma. Four months
      after surgery, the cat had intermittent vomiting, marked weight loss, and died.

PMID- 10914534
TI  - Intravascular lymphoma presenting as bilateral panophthalmitis and retinal
      detachment in a dog.
AB  - A seven-year-old, spayed female boxer was presented for sudden blindness and red
      eyes of one week's duration. Ophthalmic examination revealed bilateral uveitis
      with complete bullous retinal detachments. Initial diagnostic testing failed to
      reveal evidence of systemic disease. Cytopathology of subretinal aspirates
      confirmed the presence of macrophages with intracytoplasmic retinal pigment,
      epithelial and choroidal pigment, and monocytes. Tentative diagnoses were
      idiopathic uveitis and retinal detachment. The dog was treated with
      immunosuppressive doses of prednisone. The retinas reattached and vision
      returned. By two months, the dog became blind and systemically ill. Postmortem
      and histopathological examinations revealed intravascular lymphoma in multiple
      organs, including the eyes.

PMID- 10914535
TI  - Exophthalmos secondary to aspergillosis in a cat.
AB  - Clinical signs of orbital disease include exophthalmos, strabismus, or, less
      commonly, enophthalmos. Fungal orbital disease is uncommon. A case of nasal,
      frontal sinus, and orbital aspergillosis in a cat is described. Diagnostics for
      exophthalmos and therapy for retrobulbar abscesses are discussed.

PMID- 10914536
TI  - Vertebral subluxation following ventral cervical decompression in the dog.
AB  - Cervical intervertebral disk disease is commonly treated surgically by ventral
      decompression through a ventral slot. Nine dogs with documented vertebral
      subluxation following surgical creation of a ventral slot are reported. The
      location of the subluxation was at the fourth cervical (C4) to fifth cervical
      (C5) intervertebral space in two dogs, C5 to sixth cervical (C6) intervertebral
      space in four dogs, and C6 to seventh cervical (C7) intervertebral space in three
      dogs. The ventral slot width to vertebral body width ratio ranged from 0.39 to
      0.80, with the ratio being 0.50 or greater in seven of eight cases evaluated
      radiographically. Surgical reduction and stabilization were performed in seven of
      nine dogs.

PMID- 10914537
TI  - Perioperative risk factors for puppies delivered by cesarean section in the
      United States and Canada.
AB  - The purpose of this study was to evaluate perioperative risk factors affecting
      neonatal survival after cesarean section. Data from 807 cesarean-derived litters
      (3,908 puppies) was submitted by 109 practices in the United States and Canada.
      Survival rates immediately, two hours, and seven days after delivery were 92%
      (n=3,127), 87% (n=2,951), and 80% (n=2,641), respectively, for puppies delivered
      by cesarean section (n=3,410) and were 86% (n=409), 83% (n=366), and 75% (n=283),
      respectively, for puppies born naturally (n=498). Maternal mortality rate was 1%
      (n=9). Of 776 surgeries, 453 (58%) were done on an emergency basis. The most
      common breed of dog was bulldog (n=138; 17%). The most common methods of inducing
      and maintaining anesthesia were administration of isoflurane for induction and
      maintenance (n=266; 34%) and administration of propofol for induction followed by
      administration of isoflurane for maintenance (n=237; 30%). A model of cesarean
      derived puppies surviving to birth, between birth and two hours, and between two
      hours and seven days was designed to relate litter survival to perioperative
      factors. The following factors increased the likelihood of all puppies being
      alive: the surgery was not an emergency; the dam was not brachycephalic; there
      were four puppies or less in the litter; there were no naturally delivered or
      deformed puppies; all puppies breathed spontaneously at birth; at least one puppy
      vocalized spontaneously at birth; and neither methoxyflurane nor xylazine was
      used in the anesthetic protocol.

PMID- 10914538
TI  - Heat shock proteins--modulators of apoptosis in tumour cells.
AB  - Apoptosis is a genetically programmed, physiological method of cell destruction.
      A variety of genes are now recognised as positive or negative regulators of this
      process. Expression of inducible heat shock proteins (hsp) is known to correlate
      with increased resistance to apoptosis induced by a range of diverse cytotoxic
      agents and has been implicated in chemotherapeutic resistance of tumours and
      carcinogenesis. Intensive research on apoptosis over the past number of years has
      provided significant insights into the mechanisms and molecular events that occur
      during this process. The modulatory effects of hsps on apoptosis are well
      documented, however, the mechanisms of hsp-mediated protection against apoptosis
      remain to be fully defined, although several hypotheses have been proposed.
      Elucidation of these mechanisms should reveal novel targets for manipulating the
      sensitivity of leukaemic cells to therapy. This review aims to explain the
      currently understood process of apoptosis and the effects of hsps on this
      process. Several proposed mechanisms for hsp protection against apoptosis and the
      therapeutic implications of hsps in leukaemia are also discussed.

PMID- 10914539
TI  - Genetic heterogeneity in acute myeloid leukemia: maximizing information flow from
      MuLV mutagenesis studies.
AB  - The study of myeloid leukemia induced by slow transforming murine leukemia
      viruses (MuLV) in the laboratory mouse has led to discovery of many important
      genes with critical roles in regulating the growth, death, lineage determination
      and development of hematopoietic precursor cells. This review provides an
      overview of the susceptible strains and virus isolates that cause acute myeloid
      leukemia (AML) in mice. In addition, newer methodologies, involving the use of
      the polymerase chain reaction, that have been used to identify cancer genes
      mutated by proviral insertion in mouse models, will be discussed. As cancer is a
      multi-gene disease, a system in which pairs of oncogenic mutations are classified
      as redundant, neutral or synergistic is described. The potential to combine MuLV
      mutagenesis with recent advances in mouse transgenesis in order to model specific
      forms of myeloid leukemia or genetic pathways common in human AML will be
      discussed. Finally, a general strategy for maximizing these genetically rich
      models to foster a better understanding of AML physiology and developing
      therapies is proposed.

PMID- 10914540
TI  - Late effects in survivors of infant leukemia.
AB  - Little is known about the incidence of and risk factor for late effects of infant
      leukemia. We evaluated 19 children with acute lymphoblastic leukemia and 15 with
      acute myeloid leukemia who were diagnosed at age 12 months or younger and have
      survived for more than 5 years after the diagnosis (median length of follow-up,
      13 years; range, 5.7-29 years). Ten patients received chemotherapy alone (group
      A), 17 received chemotherapy and CNS-directed radiation therapy (CRT) (group B),
      and seven received chemotherapy, CRT and bone marrow transplantation (group C).
      The most frequently observed late sequelae included problems in growth (66% of
      survivors), learning (50%), hypothyroidism (15%), and pubertal development (12%).
      Cataract, cardiac and hearing abnormalities occurred in 6% of patients. Only
      eight patients (24%) survive without late effects. In comparison to patients in
      group A, patients in groups B and C had a higher incidence of having at least one
      late complication (P = 0.009), a greater decrease in height Z score at 5 years
      after diagnosis (P = 0.023), and a higher incidence of academic difficulties (P =
      0.004). The estimated odds of academic difficulties increased by 18% (P = 0.032)
      for each month younger in age at the time of CRT. These results indicate that
      late sequelae are common in longterm survivors of infant leukemia and are often
      related to CRT and the patient's age at the time of CRT.

PMID- 10914541
TI  - High-dose cytosine arabinoside and daunorubicin induction therapy for adult
      patients with de novo non M3 acute myelogenous leukemia: impact of cytogenetics
      on achieving a complete remission.
AB  - Cytogenetic abnormalities are used to define prognostic subgroups of acute
      myelogenous leukemia (AML) with respect to achieving complete remission (CR) and
      remaining disease free. These prognostic groups for obtaining CR were based on an
      induction regimen mainly using standard dose cytosine arabinoside (Ara-C) +
      daunorubicin (DNR). We have reviewed our experience with 122 adult patients with
      de novo non-M3 AML who were treated with high-dose (HD) Ara-C 3 g/m2 given over 3
      h every 12 h for a total of eight doses followed by DNR 60 mg/m2 daily for 2
      days. CR was obtained in 80% while 16% had refractory disease and 4% died of
      sepsis during hypoplasia. CR rate for favorable, intermediate and unfavorable
      cytogenetic groups were 87%, 79% and 62%, respectively (P = 0.32). High white
      blood cell count, age, FAB subtype and LDH levels did not adversely affect CR
      rate. Eighty-five percent of patients achieved CR with one course of treatment
      and 87% of complete responders were able to receive post remission therapy. High
      dose Ara-C/DNR appears to offer an excellent chance of achieving remission for
      patients with AML including those with poor risk cytogenetics, without an
      increase in early toxic deaths.

PMID- 10914542
TI  - Hypergranular promyelocytic leukemia: correlation between morphology and
      chromosomal translocations including t(15;17) and t(11;17).
AB  - The FAB group has reviewed 32 cases of promyelocytic leukemia and variant forms.
      By utilizing published criteria the ability to make a correct diagnosis by
      morphology with molecular genetic confirmation and to eliminate cases that did
      not have the PML/RARalpha rearrangement was excellent.

PMID- 10914543
TI  - Prognostic factors in children and adolescents with acute myeloid leukemia
      (excluding children with Down syndrome and acute promyelocytic leukemia):
      univariate and recursive partitioning analysis of patients treated on Pediatric
      Oncology Group (POG) Study 8821.
AB  - The purpose of the paper was to define clinical or biological features associated
      with the risk for treatment failure for children with acute myeloid leukemia.
      Data from 560 children and adolescents with newly diagnosed acute myeloid
      leukemia who entered the Pediatric Oncology Group Study 8821 from June 1988 to
      March 1993 were analyzed by univariate and recursive partitioning methods.
      Children with Down syndrome or acute promyelocytic leukemia were excluded from
      the study. Factors examined included age, number of leukocytes, sex, FAB
      morphologic subtype, cytogenetic findings, and extramedullary disease at the time
      of diagnosis. The overall event-free survival (EFS) rate at 4 years was 32.7%
      (s.e. = 2.2%). Age > or =2 years, fewer than 50 x 10(9)/I leukocytes, and t(8;21)
      or inv(16), and normal chromosomes were associated with higher rates of EFS (P
      value = 0.003, 0.049, 0.0003, 0.031, respectively), whereas the M5 subtype of AML
      (P value = 0.0003) and chromosome abnormalities other than t(8;21) and inv(16)
      were associated with lower rates of EFS (P value = 0.0001). Recursive
      partitioning analysis defined three groups of patients with widely varied
      prognoses: female patients with t(8;21), inv(16), or a normal karyotype (n = 89)
      had the best prognosis (4-year EFS = 55.1%, s.e. = 5.7%); male patients with
      t(8;21), inv(16) or normal chromosomes (n = 106) had an intermediate prognosis (4
      year EFS = 38.1%, s.e. = 5.3%); patients with chromosome abnormalities other than
      t(8;21) and inv(16) (n = 233) had the worst prognosis (4-year EFS = 27.0%, s.e. =
      3.2%). One hundred and thirty-two patients (24%) could not be grouped because of
      missing cytogenetic data, mainly due to inadequate marrow samples. The results
      suggest that pediatric patients with acute myeloid leukemia can be categorized
      into three potential risk groups for prognosis and that differences in sex and
      chromosomal abnormalities are associated with differences in estimates of EFS.
      These results are tentative and must be confirmed by a large prospective clinical
      trial.

PMID- 10914544
TI  - T cell receptor gamma (TCRG) gene rearrangements in T cell acute lymphoblastic
      leukemia refelct 'end-stage' recombinations: implications for minimal residual
      disease monitoring.
AB  - The T cell receptor gamma (TCRG) gene configuration was established in a large
      series of 126 T cell acute lymphoblastic leukemia (T-ALL) patients using combined
      Southern blotting (SB) and heteroduplex PCR analyses. The vast majority of TALL
      (96%) displayed clonal TCRG gene rearrangements, with biallelic recombination in
      91% of patients. A small immature subgroup of CD3- T-ALL (n = 5) had both TCRG
      genes in germline configuration, three of them having also germline TCRD genes.
      In five patients (4%) combined SB and PCR results indicated oligoclonality. In
      five rearrangements detected by SB, the Vgamma gene segment could not be
      identified suggesting illegitimate recombination. Altogether, 83% of TCRG gene
      rearrangements involved either the most upstream Vgamma2 gene (including four
      cases with interstitial deletion of 170 bp in Vgamma2) and/or the most downstream
      Jgamma2.3 segment, which can be perceived as 'end-stage' recombinations.
      Comparative analysis of the TCRG gene configuration in the major immunophenotypic
      subgroups indicated that TCRgammadelta+ T-ALL display a less mature
      immunogenotype as compared to TCRalphabeta+ and most CD3- cases. This was
      reflected by a significantly increased usage of the more downstream Vgamma genes
      and the upstream Jgamma1 segments. Comparison between adult and pediatric T-ALL
      patients did not show any obvious differences in TCRG gene configuration. The
      high frequency, easy detectability, rare oligoclonality, and frequent 'end-stage'
      recombinations make TCRG gene rearrangements principal targets for PCR-based
      detection of minimal residual disease (MRD) in T-ALL. We propose a simple
      heteroduplex PCR strategy, applying five primer combinations, which results in
      the detection of approximately 95% of all clonal TCRG gene rearrangements in T
      ALL. This approach enables identification of at least one TCRG target for MRD
      monitoring in 95% of patients, and even two targets in 84% of T-ALL.

PMID- 10914545
TI  - Kinetics of early therapeutic response as measured by quantitative PCR predicts
      survival in a murine xenograft model of human T cell acute lymphoblastic
      leukemia.
AB  - The identification of prognostic parameters and surrogate markers for defining
      patient risk has been beneficial in effectively guiding therapy and increasing
      the survival of leukemia patients. It has been hypothesized that the therapeutic
      response, as measured by a change in tumor burden during therapy, might serve as
      a new surrogate marker of survival. Here we describe the development of a murine
      SCID xenograft model of human T cell acute lymphoblastic leukemia (T-ALL), and
      the use of a sensitive, quantitative PCR assay for the measurement of tumor
      levels to investigate the relationships between tumor burden quantification,
      therapeutic response and survival. Animals engrafted with the CCRF-CEM (CEM)
      human T-ALL cell line develop leukemia that closely resembles the human disease.
      Quantitative PCR detects the expanding tumor mass in the peripheral blood of the
      animals several weeks before death. In response to induction therapy with
      chemotherapeutic agents, both the level of minimal residual disease (MRD) in
      peripheral blood at the end of therapy and the rate of tumor reduction in
      peripheral blood during therapy strongly correlated with animal survival. Thus,
      these surrogate markers, which can be measured during the early stages of
      therapy, may help improve patient survival through dynamic risk stratification.

PMID- 10914546
TI  - Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia:
      correlation with specific genotype. I. ETV6/AML1 ALLs identification.
AB  - The t(12;21)(p13;q22) fusion gene is the most frequent genetic lesion described
      in precursor B cell acute lymphoblastic leukemia (ALL) of childhood occurring in
      a quarter of cases. This gene rearrangement is associated with a good outcome
      presenting a high response rate to chemotherapy. In spite of its potential
      clinical relevance, the t(12;21) translocation usually goes undetected with
      conventional cytogenetic procedures. In the present study we utilized an
      objective flow cytometric approach (multiparametric quantitative analysis) for
      the phenotypic characterization of this type of ALL. We studied a total of 74
      precursor B-ALL children, including 21 t(12;21)+ and 53 t(12;21)- cases. Our
      results show that the t(12;21)(p13;q22)+ ALLs display a higher intensity of CD10
      (P = 0.0016) and HLADR (P = 0.005) expression together with lower levels of the
      CD20 (P = 0.01), CD45 (P = 0.01), CD135 (P = 0.003) and CD34 (P = 0.03) antigens
      as compared to the t(12;21) cases. Moreover, as regards CD34 expression, we
      observed a more heterogeneous antigen expression within individual patients with
      higher coefficients of variation (median of 202 vs 88, P = 0.0001). A multi
      variate analysis disclosed that with the immunophenotypic approach used
      identification of t(12;21)+ cases can be achieved with a sensitivity of 86% and a
      specificity of 100%. We conclude that childhood precursor B-ALL carrying the
      t(12;21) translocation display characteristic phenotypic features which could
      provide a rapid, simple, sensitive and specific screening method to select for
      those cases that should undergo confirmatory molecular analysis.

PMID- 10914547
TI  - Detection of acute leukemia cells with mixed lineage leukemia (MLL) gene
      rearrangements by flow cytometry using monoclonal antibody 7.1.
AB  - Translocations involving 11q23 are among the most common genetic abnormalities in
      hematologic malignancies, occurring in approximately 5-10% of acute lymphoblastic
      leukemia (ALL) and 5% of acute myeloblastic leukemia (AML). In 11q23
      translocations, the mixed lineage leukemia (MLL) gene on chromosome 11, band q23,
      is usually disrupted. The human homologue of the rat NG2 chondroitin sulfate
      proteoglycan molecule, as detected by the monoclonal antibody (moab) 7.1, was
      shown to be expressed on leukemic cells with MLL rearrangements of children with
      acute leukemia. We further investigated the reactivity of the moab 7.1 on 533
      cell samples of adults (n = 215) and children (n = 318) with acute leukemias (271
      AML, 217 B-lineage ALL, 37 T-lineage ALL, eight CD7+ CD56+ myeloid/natural killer
      cell precursor acute leukemias) by flow cytometry. In AML, 38 samples were
      positive for moab 7.1 ('20%-cut-off-level'). These moab 7.1-positive AML cases
      revealed a myelomonocytic-differentiated immunophenotype with coexpression of the
      NK cell marker CD56 in 33 of 38 cases. Two of eight cell samples of the recently
      described CD7+ CD56+ myeloid/natural killer cell precursor acute leukemia entity
      reacted with moab 7.1. In ALL, 35 samples mostly of the pro-B-ALL subtype (33 pro
      B-ALL, one common-ALL, one pre-B-ALL) were positive for moab 7.1. 58 (81%) of 72
      samples with MLL rearrangements were positive for moab 7.1 including 28/31 with a
      t(4;11), 16/17 with a t(9;11), 3/5 with a t(11;19), and 2/6 with a del(11)(q23).
      All moab 7.1-positive ALL (n = 34) and childhood AML (n = 17) cases revealed MLL
      rearrangements as detected by Southern blot analysis and RT-PCR. However, 11
      adults with AML, and one adult with moab 7.1-positive CD7+ CD56+ myeloid/natural
      killer cell precursor acute leukemia were negative for MLL rearrangements as
      proved by Southern blot analysis. We conclude that moab 7.1 is a sensitive but
      not entirely specific marker for the identification of 11q23-associated AML and
      ALL by flow cytometry in children and adults.

PMID- 10914548
TI  - Expression of CD44 variant exons in acute myeloid leukemia is more common and
      more complex than that observed in normal blood, bone marrow or CD34+ cells.
AB  - CD44 is an adhesion molecule that is expressed on hematopoietic cells and has
      been implicated in the interactions between bone marrow stromal layers and
      hematopoietic progenitors. The expression of variant forms of CD44, particularly
      forms containing exon v6, have been associated with poor prognosis in a number of
      hematological malignancies. The expression of CD44 variants on normal bone marrow
      (BM), peripheral blood (PBMC) and CD34+ hematopoietic progenitors was compared
      with those expressed on blasts from 30 patients with acute myeloid leukemia
      (AML). Normal BM, PBMC and CD34+ progenitor cells were negative for all variants
      tested by flow cytometry. In contrast exon v3 was expressed on 13%, v4 on 67%, v5
      on 19%, v6 on 7% and v7 on 65% of AML cases. RT-PCR and Southern blotting
      revealed the expression of exons v3, v6, v8, v9 and v10 in normal bone marrow and
      peripheral blood mononuclear cells and the expression of exons v3, v6, v8 and v10
      in CD34+ progenitors. A more complex pattern of variant exon expression was
      observed in leukemic samples in comparison to normal hematopoietic cells. Sixty
      two percent of AML cases expressed exon v3 and 70% exon v6. Exons v4 and v5 were
      not detected while exons v7, v8, v9 and v10 were detected in 21, 83, 71 and 92%
      of cases, respectively. In summary, our data demonstrate a striking increase in
      the complexity of CD44 variant expression in cells from patients with AML, along
      with surface expression of some variant CD44 proteins. Further analysis will be
      directed at how these alter the interaction of leukemic blasts with the bone
      marrow microenvironment and their diagnostic, prognostic and therapeutic
      potential.

PMID- 10914549
TI  - Chromatin remodeling gene SMARCA5 is dysregulated in primitive hematopoietic
      cells of acute leukemia.
AB  - We identified a subset of genes involved in chromatin remodeling whose mRNA
      expression changes in differentiating mouse erythroleukemia (MEL) cells. We
      furthermore tested their mRNA expression patterns in normal and malignant CD34+
      bone marrow cells. SMARCA5, imitation switch gene homologue, was rapidly silenced
      during in vitro erythroid differentiation of MEL cells whereas it was up
      regulated in CD34+ hematopoietic progenitors of acute myeloid leukemia (AML)
      patients. Moreover, SMARCA5 mRNA levels decreased in AML CD34+ progenitors after
      the patients achieved complete hematologic remission. We detected high levels of
      SMARCA5 mRNA in murine bone marrow and spleen and monitored its expression in
      these hematopoietic tissues during accelerated hematopoiesis following hemolytic
      anemia induced by phenylhydrazine. SMARCA5 expression levels decreased after the
      onset of accelerated erythropoiesis. Our data suggest that both in vitro and in
      vivo induction of differentiation is followed by down-regulation of SMARCA5
      expression. In CD34+ AML progenitors over-expression of SMARCA5 may thus
      dysregulate the genetic program required for normal differentiation.

PMID- 10914550
TI  - The PEBP2beta/CBF beta-SMMHC chimeric protein is localized both in the cell
      membrane and nuclear subfractions of leukemic cells carrying chromosomal
      inversion 16.
AB  - The chromosomal inversion (16)(p13q22), which is associated with the M4
      eosinophilia subtype of human acute myeloid leukemia, causes the fusion of two
      distinct genes. The polypeptide encoded by the chimeric gene, PEBP2p/CBFp-SMMHC,
      retains the ability to interact with, and dominantly interfere with the function
      of proteins possessing the Runt homology domain. The Runt protein homologs
      constitute the DNA binding subunit of the PEBP2/CBF transcription factor. We
      examined the subcellular localization of PEBP2beta/CBFbeta-SMMHC, as well as that
      of Runt protein homologs in leukemic cells carrying inversion 16 by immunoblot
      analysis. A significant amount of the PEBPbeta/CBFbeta-SMMHC protein was
      recovered from the nuclear fraction along with the Runt protein homologs.
      Furthermore, some of both polypeptides was retained in the DNA pellet that
      represents the material remaining after extraction of nuclear fraction with high
      salt. These observations suggest that the so-called dominant interfering effect
      of PEBPbeta/CBFbeta-SMMHC on PEBP2/CBF occurs inside the nucleus. In addition, we
      could detect PEBP2beta/CBFbeta-SMMHC in the cytoplasmic membrane fraction as
      well. The function of this membrane-located PEBP2beta/CBFbeta-SMMHC, if any,
      appears to be unrelated to that of Runt protein homologs.

PMID- 10914551
TI  - Ectopic expression of c-myc fails to overcome downregulation of telomerase
      activity induced by herbimycin A, but ectopic hTERT expression overcomes it.
AB  - Telomerase plays a key role in the maintenance of chromosomal stability in
      tumors, but the mechanism regulating telomerase activity is still unclear. Recent
      studies have suggested that c-myc may be vital for regulation of hTERT mRNA
      expression and telomerase activity. In this study, we investigated the changes of
      telomerase activity and telomerase-related genes induced by herbimycin A in K562
      human chronic myelogeous leukemic cells. Telomerase activity showed a biphasic
      pattern in herbimycin A-treated K562 cells. Initially, the telomerase activity
      decreased along with the decline of cells in S and G2/M phases, but it recovered
      slightly at the end of treatment. Expression of mRNA for the telomerase catalytic
      subunit (hTERT) was decreased before the decline of telomerase activity, and
      increased slightly before the reactivation of telomerase activity. During
      herbimycin A treatment, both c-myc and cyclin D1 mRNA showed transient
      downregulation before the increase of G1 cells. Herbimycin A treatment caused the
      downregulation of both telomerase activity and hTERT mRNA in cyclin D1
      transfected K562 cells, while telomerase activity was partially restored in c-Myc
      transfected cells. In contrast, hTERT-transfected K562 cells maintained a high
      level of telomerase activity during herbimycin A treatment. Neither the template
      RNA component of telomerase (hTERC) nor telomerase-associated protein (TEP-1)
      were altered in any of the transfected K562 cells. These results indicate that
      telomerase activity is mainly regulated by hTERT, and that c-Myc protein is one
      of the positive regulators of hTERT in leukemic cells but is not enough to
      counteract the downregulation of telomerase activity by herbimycin A completely.

PMID- 10914552
TI  - Study of apoptosis-related responses of leukemic blast cells to in vitro
      anthracycline treatment.
AB  - Anthracyclines trigger an apoptotic cell death but their molecular targets are
      not totally explored. We investigated the apoptotic response of blast cells and
      lymphocytes from medullary samples of 31 de novo acute leukemia. Mononuclear
      cells were treated in vitro by therapeutic concentrations of either daunorubicin
      (DNR) or idarubicin (IDA) for 1 h, washed and cultured for 18 h. A multivariate
      analysis using flow cytometry and a CD45 gating on lymphocytes and blast cells
      was performed. DNR and IDA induced a Fas enhancement on both leukemic and normal
      cells. In blast cells the DEVDases were activated and the caspase 3 was cleaved
      in relation to phosphatidyl serine exposure, showing a caspase-dependent pathway
      in anthracycline-induced apoptosis. Apoptotic percentages were always higher for
      blast cells than for lymphocytes, confirming that anthracycline toxicity mainly
      affected tumor cells. Moreover, drug-induced apoptosis was not related to
      spontaneous apoptosis, suggesting that variations in response intensities were
      due to individual variations of sensitivity rather than to programmed life span
      time. The apoptotic response of P-glycoprotein-expressing blast cells was not
      significant, giving biological argument for the poor prognosis of multidrug
      resistance leukemia. Finally, Fas induction and anthracycline-induced apoptosis
      on blast cells were significantly higher when a complete remission was achieved,
      thus shedding light on potential new prognostic factors in acute leukemia.

PMID- 10914554
TI  - The SH2 domain-containing protein tyrosine phosphatase SHP-1 is induced by
      granulocyte colony-stimulating factor (G-CSF) and modulates signaling from the G
      CSF receptor.
AB  - The SH2 domain-containing protein tyrosine phosphatase SHP-1 is expressed widely
      in the hematopoietic system. SHP-1 has been shown to negatively control signal
      transduction from many cytokine receptors by direct docking to either the
      receptor itself, or to members of the Jak family of tyrosine kinases which are
      themselves part of the receptor complex. Motheaten and viable motheaten mice,
      which are deficient in SHP-1, have increased myelopoiesis and show an
      accumulation of morphologically and phenotypically immature granulocytes,
      suggesting a role for SHP-1 in granulocytic differentiation. Here, we report that
      SHP-1 protein levels are up-regulated during the granulocyte colony-stimulating
      factor (G-CSF)-mediated granulocytic differentiation of myeloid 32D cells.
      Enforced expression of SHP-1 in these cells leads to decreased proliferation and
      enhanced differentiation, while introduction of a catalytically inactive mutant
      produces increased proliferation and results in a delay of differentiation. In
      vitro binding revealed that the SH2 domains of SHP-1 are unable to associate
      directly with tyrosine-phosphorylated G-CSF receptor (G-CSF-R). Furthermore, over
      expression of SHP-1 in Ba/F3 cells expressing a G-CSF-R mutant lacking all
      cytoplasmic tyrosines also inhibited proliferation. Together, these data suggest
      that SHP-1 directly modulates G-CSF-mediated responses in hematopoietic cells via
      a mechanism that does not require docking to the activated G-CSF-R.

PMID- 10914553
TI  - Protease inhibitor-induced apoptosis: accumulation of wt p53, p21WAF1/CIP1, and
      induction of apoptosis are independent markers of proteasome inhibition.
AB  - Inhibitors of proteases are currently emerging as a potential anti-cancer
      modality. Nonselective protease inhibitors are cytotoxic to leukemia and cancer
      cell lines and we found that this cytotoxicity is correlated with their potency
      as inhibitors of the proteasome but not as inhibitors of calpain and cathepsin.
      Highly selective inhibitors of the proteasome were more cytotoxic and fast-acting
      than less selective inhibitors (PS341>>ALLN>>ALLM). Induction of wt p53
      correlated with inhibition of the proteasome and antiproliferative effect in
      MCF7, a breast cancer cell line, which was resistant to apoptosis caused by
      proteasome inhibitors. In contrast, inhibitors of the proteasome induced
      apoptosis in four leukemia cell lines lacking wt p53. The order of sensitivity of
      leukemia cells was: Jurkat>HL60> or =U937>>K562. The highly selective proteasome
      inhibitor PS-341 induced cell death with an IC50 as low as 5 nM in apoptosis
      prone leukemia cells. Cell death was preceded by p21WAF1/CIP1 accumulation, an
      alternative marker of proteasome inhibition, and by cleavage of PARP and Rb
      proteins and nuclear fragmentation. Inhibition of caspases abrogated PARP
      cleavage and nuclear fragmentation and delayed, but did not completely prevent
      cell death caused by PS-341. Reintroduction of wt p53 into p53-null PC3 prostate
      carcinoma cells did not increase their sensitivity to proteasome inhibitors.
      Likewise, comparison of parental and p21-deficient cells demonstrated that
      p21WAF1/CIP1 was dispensable for proteasome inhibitor-induced cytotoxicity. We
      conclude that accumulation of wt p53 and induction of apoptosis are independent
      markers of proteasome inhibition.

PMID- 10914555
TI  - Induction of IW32 erythroleukemia cell differentiation by p53 is dependent on
      protein tyrosine phosphatase.
AB  - The biological activity of p53 in IW32 erythroleukemia cells was investigated.
      IW32 cells had no detectable levels of p53 mRNA and protein expression. By
      transfecting a temperature-sensitive mutant p53 cDNA, tsp53val135, into the
      cells, we have established several clones stably expressing the mutant p53
      allele. At permissive temperature, these p53 transfectants were arrested in G1
      phase and underwent apoptosis. Moreover, differentiation along the erythroid
      pathway was observed as evidenced by increased benzidine staining and mRNA
      expression of beta-globin and the erythroid-specific delta-aminolevulinic acid
      synthase (ALAS-E). Treatment of cells with protein tyrosine phosphatase inhibitor
      vanadate blocked the p53-induced differentiation, but not that of cell death or
      growth arrest. Increased protein tyrosine phosphatase activity as well as mRNA
      levels of PTPbeta2 and PTPepsilon could be observed by wildtype p53
      overexpression. These results indicate that p53 induced multiple phenotypic
      consequences through separate signal pathways in IW32 erythroleukemia cells, and
      protein tyrosine phosphatase is required for the induced differentiation.

PMID- 10914556
TI  - Characterization of a novel HHV-8-positive cell line reveals implications for the
      pathogenesis and cell cycle control of primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) represents a peculiar type of B cell lymphoma
      which associates with HHV-8 infection and preferentially grows in liquid phase in
      the serous body cavities. In this report, we provide the detailed
      characterization of a newly established PEL cell line, termed CRO-AP/6. The cell
      line was obtained from the pleural effusion of a HIV-positive patient with PEL.
      Its derivation from the tumor clone was established by immunogenotypic analysis.
      Detailed phenotypic investigations defined that CRO-AP/6 reflects pre-terminally
      differentiated B cells expressing the CD138/syndecan-1 antigen. Karyotypic
      studies of CRO-AP/6 identified several chromosomal abnormalities, whereas
      genotypic studies ruled out the involvement of molecular lesions associated with
      other types of B cell lymphoma. Both CRO-AP/6 and the parental tumor sample
      harbored infection by HHV-8. Conversely, EBV infection was present in the
      parental tumor sample although not in CROAP/6, indicating that CRO-AP/6
      originated from the selection of an EBV-negative tumor subclone. The pattern of
      viral (HHV-8 v-cyclin) and cellular (p27Kip1) regulators of cell cycle expressed
      by CRO-AP/6, together with the results of growth fraction analysis, point to
      abrogation of the physiological inverse relationship between proliferation and
      p27Kip1 expression. Also, both CRO-AP/6 and the parental tumor sample display
      biallelic inactivation of the DNA repair enzyme gene O6-methylguanine-DNA
      methyltransferase (MGMT) by promoter methylation. Overall, the CRO-AP/6 cell line
      may help understand cell cycle control of PEL cells, may clarify the relative
      contribution of HHV-8 and EBV to the disease growth and development and may
      facilitate the identification of recurrent cytogenetic abnormalities highlighting
      putative novel cancer related loci relevant to PEL.

PMID- 10914558
TI  - Double minute chromosomes and c-MYC amplification in a child with secondary
      myelodysplastic syndrome after treatment for acute lymphoblastic leukemia.

PMID- 10914557
TI  - Safety of autologous hematopoietic stem cell transplantation in patients with
      multiple myeloma and chronic renal failure.
AB  - Patients with multiple myeloma (MM) and chronic renal failure have generally been
      excluded from myeloablative therapy programs followed by hematopoietic stem cell
      support because of the potential increase in transplant-related morbidity and
      mortality. We here report our experience treating six MM patients with moderate
      to severe renal insufficiency, with autologous stem cell transplantation. One of
      these patients required chronic hemodialysis since the diagnosis of MM was made.
      Peripheral blood stem cell collection was performed with either cyclophosphamide
      5.5-7 g/m2 + G-CSF, 5 microg/kg/day (patients 1-3, 5 and 6) or G-CSF, 15
      microg/kg/day alone (patient No. 4). Four patients (Nos 1-4) received
      autotransplant as front-line therapy, while the last two patients were treated in
      relapse, which occurred following prior autologous stem cell transplantation in
      support of melphalan, 200 mg/m2 (No. 5) or maintainance therapy with alpha
      interferon (No. 6). High-dose chemotherapy administered as preparation to
      transplant included busulfan 12 mg/kg + melphalan 80 mg/m2 (patients 1-3 and 6)
      or melphalan 80 mg/m2 alone (patients 4 and 5) in order to reduce mucosal damage.
      Following transplant, prompt and sustained recovery of hematopoiesis was
      documented in all the patients; 500 PMN/microI and 20000 platelets/microI were
      reached after a median of 13 and 14 days, respectively. None of the patients
      suffered from WHO grade 3-4 infectious complications. Transplant-related toxicity
      included grade 3-4 oral mucositis (patients 1, 4 and 5) and veno-occlusive
      disease (patient No. 3). Renal function either improved or remained stable
      throughout the transplant period. All the patients but one responded to therapy,
      three of them are progression free after 2, 15 and 26 months; two relapsed after
      16 and 4 months and one died from cholangiocarcinoma 7 months after transplant,
      while still in remission. Although our experience is limited so far, these
      results appear promising and support the investigational use of myeloablative
      therapy in MM patients with chronic renal failure.

PMID- 10914559
TI  - Mutation analysis of the WT1 gene in secondary leukemia.

PMID- 10914560
TI  - Expression of cyclins D-type in B-chronic lymphoproliferative disorders.

PMID- 10914562
TI  - Cytogenetic and FISH analyses in five patients with hypoplastic bone marrow.

PMID- 10914561
TI  - Double fusion signal BCR/ABL, detected by FISH on chromosomes 9 and 22 in a child
      with ALL.

PMID- 10914563
TI  - Life-threatening paroxysmal supraventricular tachycardia developed during
      granulocyte transfusion therapy for neutropenia-related infection.

PMID- 10914564
TI  - Allelic losses and genetic instabilities of PTEN and p73 in non-Hodgkin
      lymphomas.

PMID- 10914565
TI  - Significance of micromegakaryocytes in Philadelphia chromosome-positive acute
      lymphoblastic leukemia.

PMID- 10914567
TI  - Chemical development of latent fingerprints: computational design of ninhydrin
      analogues.
AB  - The design of chemical compounds for development of latent fingerprints is
      explored computationally. Our main findings are: (a) We show why past attempts to
      improve the widely used ninhydrin gave relatively small improvements (referring
      to color only). The optical transition is connected with a "transition core" and
      therefore is influenced little by substitution on the aromatic rings. (b) We
      propose new analogues of ninhydrin with a significant potential such as thiono
      derivatives.

PMID- 10914566
TI  - CD19+ and CD20+ B cells from the peripheral blood of patients with multiple
      myeloma are not infected with human herpesvirus 8.

PMID- 10914568
TI  - Evaluation of 1,2-indanedione and 5,6-dimethoxy-1,2-indanedione for the detection
      of latent fingerprints on porous surfaces.
AB  - The ability of 1,2-indanedione and 5,6-dimethoxy-1,2-indanedione to detect latent
      prints on porous surfaces, as compared to DFO and ninhydrin, has been evaluated.
      Comparisons of prints developed under various conditions determined the optimum
      development conditions for the new reagents. The indanediones tested were found
      to have lower detection limits for glycine. The carrier solvent used was found to
      affect the quality of the prints developed. In Arklone, the new reagents
      developed prints that displayed superior luminescence to those developed with
      DFO. In HFE 7100, 1,2-indanedione and 5,6-dimethoxy-1,2-indanedione gave superior
      luminescence to DFO after zinc salt treatment and cooling with liquid nitrogen,
      both of which improve the luminescence of prints developed with 1,2-indanediones.
      1,2-Indanediones could offer less expensive but effective alternatives to DFO.
      With further optimization, the new reagents may supersede DFO as the method of
      choice for the detection of latent fingerprints on porous surfaces.

PMID- 10914569
TI  - Photoluminescent CdS/dendrimer nanocomposites for fingerprint detection.
AB  - CdS/dendrimer nanocomposites with a range of concentrations of the
      photoluminescent semiconductor nanocluster and the dendrimer are prepared in
      methanol and 1:9 methanol:water solutions. The solutions are utilized for
      detection of cyanoacrylate ester fumed and unfumed fingerprints on polyethylene
      and aluminum foil.

PMID- 10914570
TI  - Method for characterization of adhesion properties of trace explosives in
      fingerprints and fingerprint simulations.
AB  - The near inevitable transfer of explosive particulate matter through fingerprints
      makes it possible to detect concealed explosives through surface sampling.
      Repeatable and well-characterized fingerprint simulation facilitates quantitative
      comparison between particulate sampling methods for subsequent detection of trace
      explosive residues. This study employs a simple, but reproducible sampling system
      to determine the accuracy of a fingerprint simulation. The sampling system uses a
      gas jet to entrain particles from a substrate and the resulting airborne
      particles are then aspirated onto a Teflon filter. A calibrated Barringer IonScan
      400 ion mobility spectrometer was used to determine the mass of explosive
      material collected on the filter. The IonScan 400 was calibrated with known
      masses of 2,4,6-trinitrotoluene (TNT). The resulting calibration curve is in good
      agreement with that obtained by Garofolo et al. (1994) for an earlier model of
      the instrument. The collection efficiency of the sampling system was measured for
      three particle sizes (8.0. 10.0, and 13.0 microm) using spherical polystyrene
      particles laced with known quantities of TNT. Collection efficiency ranged from
      less than 1% for the larger particles to 5% for the smaller particles. Particle
      entrainment from the surface was monitored with dark field imaging of the
      remaining particles. The sampling system was then applied to two C4 test samples-
      a fingerprint transfer and a dry Teflon transfer. Over 100 ng of RDX was
      collected from the dry transfer sample, while less than 1 ng was collected from
      the fingerprint transfer. Possible explanations for this large difference are
      presented based on the system calibration.

PMID- 10914571
TI  - ABTS: a safe alternative to DAB for the enhancement of blood fingerprints.
AB  - The use of 2,2'-azino-di-[3-ethylbenzthiazolinesulfonate(6)] diammonium salt
      (ABTS) for the enhancement of fingerprints in blood has been investigated.
      Optimal pH conditions and H2O2 concentrations have been determined using UV/Vis
      spectroscopy. ABTS is an effective and safe noncarcinogenic (though more
      expensive) alternative to the presently used 3,3'-diaminobenzidine (DAB) for the
      development of blood fingerprints, especially on porous surfaces. The bright
      green color of the oxidized ABTS is an advantage on certain colored surfaces
      where the dark brown color of DAB does not stand out well from the background.
      Development with ABTS does not interfere with subsequent DAB treatment, making
      ABTS a "nothing-to-lose" reagent. ABTS can be used after ninhydrin treatment, but
      the reverse is not the case.

PMID- 10914572
TI  - A sandwich enzyme-linked immunosorbent assay for ABO blood typing of semen by
      using anti-p 84 monoclonal antibody as a marker of blood group substance in
      semen.
AB  - A blood group substance (BGS), a protein with ABH antigenic activity, was
      isolated from human seminal plasma and designated as p 84 (Sato, 1995). We have
      developed a method for determining the ABO blood type of semen by performing a
      sandwich enzyme-linked immunosorbent assay (ELISA) in which p 84 is captured with
      an anti-p 84 monoclonal antibody, and evaluated the specificity and sensitivity
      of this method. Although BGS activity was detected in semen sensitively by this
      method, it was not detected in saliva, urine, breast milk, blood or vaginal
      secretions. Since the concentration of p 84 in semen was independent of the
      secretion status, the status can be determined as non-secretor when p 84 but not
      BGS activity was detected. To determine the stability of BGS activity on p 84,
      dried stains of semen on filter paper were kept at 4, 26, and 37 degrees C for 8
      months, 2 years and 1 month, respectively, and their BGS activities were
      examined. After 8 months at 4 degrees C, over 60% of the original BGS activity
      was recovered from the stain. The activity could be detected even from a square
      as small as 0.25 by 0.25 cm. After 1 month at 37 degrees C and 2 years at 26
      degrees C, 31 and 20% of the BGS activity, respectively, still remained. It could
      be detected from the pieces of 1.0 by 1.0 cm and 0.5 by 0.5 cm squares, kept for
      1 month at 37 degrees C and 2 years at 26 degrees C, respectively. Finally, semen
      was mixed with saliva or blood at varying volumetric ratios and used for the
      sources of dried stains. The BGS activity of p 84 could be detected in the stains
      until the ratio between semen and saliva or blood reached 1:4. We conclude that
      this sandwich ELISA offers a more sensitive and specific method for determining
      the ABO blood type of semen samples obtained from sexual assault victims than
      existing methods, such as the conventional absorption-elution and classical
      hemagglutination-inhibition tests.

PMID- 10914573
TI  - Improved method for shooting distance estimation. Part 1. Bullet holes in
      clothing items
AB  - An improved method for firing distance estimation on clothing is described. The
      novel part of the method includes transfer of total nitrite (nitrite ions and
      smokeless powder residues) from the target to an adhesive lifter. After the
      transfer, lead and copper deposits around the bullet entrance hole are visualized
      by rhodizonate and rubeanic acid, respectively. The Modified Greiss Test is
      carried out after alkaline hydrolysis of the smokeless powder residues on the
      adhesive lifter.

PMID- 10914574
TI  - Gelatinase A in human dentin as a new biochemical marker for age estimation.
AB  - Dentin proteins from 24-individual permanent molars from patients aged 15 to 73
      years were sequentially extracted, with guanidinium chloride (G1-extract) and
      then with EDTA; after demineralization, the material was again extracted with
      guanidinium chloride (G2-extract). Extracts were analyzed by SDS-PAGE
      electrophoresis and the gels were processed for zymography to detect
      gelatinolytic activities. The patterns of gelatinase A distribution differed in
      the different dentin protein fractions, and the changes varied with age.
      Significant differences were detected in gelatinase A in G2-extracts between
      individual younger than 20 years old and the rest of the sample (chi2exp =
      19.429; 1 d.f.; p < or = 0.001). The incidence of true and false positives and
      negatives, and sensitivity and specificity for the presence of gelatinase A in
      dentin extracts, were calculated. Determination of gelatinase A in human dentin
      may be a useful marker to estimate age, especially when other morphological
      methods are of limited usefulness.

PMID- 10914575
TI  - Anatomical location of bitemarks and associated findings in 101 cases from the
      United States.
AB  - The purpose of this paper is to update and confirm previous studies that examined
      the anatomical location of human bitemarks. This information is useful to
      forensic odontologists and pathologists, physicians, and coroners who must be
      familiar with the most likely locations of bitemarks. The data are also useful
      for those involved in bitemark research. Using the legal database "Lexis," 101
      bitemark cases were identified from the United States Courts of Appeal. Cases
      were included in the study if they provided details concerning the bitemark, such
      as anatomical location, number of injuries, and information concerning the
      victim. Information on 148 bites was collated. These data are presented in
      tabular and graphical form to allow comparisons between males and females,
      victims and perpetrators, adults and children, and the crime types associated
      with human bites.

PMID- 10914576
TI  - Psychological factors in the determination of suicide in self-inflicted gunshot
      head wounds.
AB  - Self-inflicted contact gunshot wounds to the head have usually been considered
      presumptive of suicide. This study evaluates whether sufficient psychological
      data are gathered in such cases to support a manner of death determination of
      suicide. We suggest that law enforcement agencies and coroner's departments do
      not fully explore the decedent's state of mind at the time of death. We studied
      the first 50 consecutive deaths in 1993 in a major metropolitan county due to
      self-inflicted gunshot wounds to the head. The sample consists primarily of
      unmarried, white males, with a median age of 35 years, who displayed psychiatric
      disturbance, primarily depression, before their death. Younger individuals were
      often under the influence of alcohol and/or drugs at the time of death.
      Stressors, such as the loss of a loved one, are common among young and middle
      aged persons, while serious health problems are found among the majority of
      middle-aged and elderly individuals. Many of the findings of this study are
      consistent with the literature regarding individuals who commit suicide. Although
      data on many important psychological risk factors are missing in most cases,
      sufficient psychological material is gathered about the decedent's mental
      condition at the time of death to support a suicide determination.

PMID- 10914577
TI  - Partial sequencing of the cytochrome oxydase b subunit gene I: a tool for the
      identification of European species of blow flies for postmortem interval
      estimation.
AB  - The identification of insects found on a dead body can lead to the estimation of
      the time of death (postmortem interval). We report an updated version of an
      established method based on sequence analysis of PCR products from a region of
      the cytochrome b oxidase subunit I mitochondrial gene of different members of the
      family Calliphoridae, by sequencing six European species: Lucilia sericata
      (Meigen), Lucilia caesar (Linne), Lucilia illustris (Meigen), Calliphora vicina
      (Robineau-Desvody), Calliphora vomitoria (Linne), Protophormia terraenovae
      (Robineau-Desvody) and one Guianese species: Cochliomyia macellaria (Fabricius).
      This technique provided clear results when applied to the larvae and we also
      report the identification of empty puparia.

PMID- 10914578
TI  - Minimum and maximum development rates of some forensically important
      Calliphoridae (Diptera).
AB  - Blow fly development rates are frequently used to estimate elapsed time since
      death in homicide investigations in the first few weeks after death. However, in
      order to make more precise estimates of time since death, accurate developmental
      data must be generated for all carrion species, and at temperatures that are
      comparable with those found at crime scenes. This paper presents developmental
      rates determined for five forensically important species in British Columbia,
      Phormia regina (Meigen), Phaenicia sericata (Meigen), Eucalliphora latifrons
      (Hough), Lucilia illustris (Meigen), and Calliphora vicina Robineau-Desvoidy, at
      several temperatures.

PMID- 10914579
TI  - Complications following insertion and replacement of percutaneous endoscopic
      gastrostomy (PEG) tubes.
AB  - Percutaneous endoscopic gastrostomy (PEG) tube insertion was introduced in 1980
      as an alternative to nasogastric tubes and surgically placed gastrostomy tubes.
      The procedure is indicated in those patients who have an inability to sustain
      adequate nutrition in the presence of a functioning gastrointestinal tract. We
      report four deaths that arose within a ten-week period in 1998.

PMID- 10914580
TI  - Decomposition patterns in terrestrial and intertidal habitats on Oahu Island and
      Coconut Island, Hawaii.
AB  - Decomposition studies were conducted at two sites on the Island of Oahu, Hawaii,
      to compare patterns of decomposition and arthropod invasion in intertidal and
      adjacent terrestrial habitats. The animal model used was the domestic pig. One
      site was on Coconut Island in Kaneohe Bay on the northeast side of Oahu, and the
      second was conducted in an anchialine pool located at Barber's Point Naval Air
      Station on the southwest shore of Oahu. At both sites, the terrestrial animal
      decomposed in a manner similar to what has been observed in previous studies in
      terrestrial habitats on the island of Oahu. Rate of biomass depletion was slower
      in both intertidal studies, and decomposition was primarily due to tide and wave
      activity and bacterial decomposition. No permanent colonization of carcasses by
      insects was seen for the intertidal carcass at Coconut Island. At the anchialine
      pool at Barber's Point Naval Air Station, Diptera larvae were responsible for
      biomass removal until the carcass was reduced below the water line and, from that
      point on, bacterial action was the means of decomposition. Marine and terrestrial
      scavengers were present at both sites although their impact on decomposition was
      negligible. Five stages of decomposition were recognized for the intertidal
      sites: fresh, buoyant/floating, deterioration/disintegration, buoyant remains,
      and scattered skeletal.

PMID- 10914581
TI  - Postmortem redistribution of morphine and its metabolites.
AB  - The postmortem redistribution of morphine, morphine-3-glucuronide, morphine-6
      glucuronide and total morphine was assessed in 40 heroin-related deaths. In blood
      taken from subclavian, heart, and femoral regions, concentrations of morphine and
      its metabolites were similar. While there was a trend for higher concentrations
      in heart blood, when compared with femoral or subclavian blood, this was not
      significant. There was also no significant difference in concentrations between
      admission and autopsy blood in which the postmortem interval was on average 59 h.
      From our observations, significant postmortem redistribution of morphine and its
      metabolites seems unlikely.

PMID- 10914583
TI  - Postmortem forensic toxicology of trazodone.
AB  - Trazodone is a popular antidepressant medication that has been available for
      approximately 30 years. It has a reputation as a safe drug with relatively few
      reported fatalities attributed solely to it. We review the pharmacology and
      forensic toxicology of trazodone and report toxicology and cause and manner of
      death in a series of 37 deaths in which trazodone was detected. Although the
      normal upper therapeutic blood concentration for trazodone is about 2 mg/L,
      fatalities are rarely attributed solely to it at blood concentrations below 9
      mg/L. Considering the pharmacology of the drug, potential interactions between
      other drugs with serotonin reuptake properties need to be considered, as does the
      increased susceptibility to the toxic effects in patients with pre-existing heart
      disease. In the cases reviewed, none were attributed solely to trazodone,
      although trazodone was frequently present together with other serotonergic drugs,
      such as the selective serotonin reuptake inhibitors like fluoxetine and
      sertraline. Ten cases had blood trazodone concentrations above 2 mg/L. Of these
      cases, trazodone played a primary role in the death of three subjects, with blood
      concentrations all greater than 9 mg/L. We confirm the conclusions of others that
      trazodone is a relatively safe drug except in massive overdose, although its
      toxicity may be influenced by the presence of other drugs and underlying
      pathophysiology.

PMID- 10914582
TI  - Determining the state of the deceased during cardiopulmonary resuscitation from
      tissue distribution patterns of intubation-related lidocaine.
AB  - The objective of this study was to determine whether the concentrations of
      lidocaine, used for endotracheal intubation, in body fluids and tissues reflect
      the state of the circulation of the deceased during cardiopulmonary
      resuscitation. The tissue distribution of lidocaine was investigated in seven
      individuals (Cases 1-7) who underwent medical treatment with endotracheal
      intubation using Xylocaine jelly (a 2% lidocaine hydrochloride preparation),
      before being pronounced dead. Six patients (Cases 1-6) had cardiopulmonary arrest
      on arrival at hospital. In Cases 1-4, there was no restoration of heartbeat
      during cardiopulmonary resuscitation. However, systemic distribution of
      intubation-related lidocaine was observed and the kidney-to-liver ratios of
      lidocaine were less than 1. In Cases 5 and 6, the heartbeat resumed temporarily
      with cardiac massage, and a kidney-to-liver lidocaine ratio greater than 1 was
      observed. In Case 7, where the patient was comatose upon admission to hospital,
      the kidney-to-liver ratio of lidocaine was also greater than 1. These phenomena
      were substantiated in animal experiments. Our results indicate that the
      absorption of tracheal lidocaine during the artificial circulation resulting from
      cardiopulmonary resuscitation results in a kidney to liver ratio of less than 1,
      whereas absorption during natural circulation gives a ratio greater than 1. The
      kidney-to-liver ratio of intubation-related lidocaine may give useful information
      on the state of a patient during cardiopulmonary resuscitation.

PMID- 10914584
TI  - Optimization of solid-phase microextraction (SPME) for the recovery of explosives
      from aqueous and post-explosion debris followed by gas and liquid chromatographic
      analysis
AB  - Solid-phase microextraction (SPME) has been evaluated for the recovery of
      explosives residues from aqueous samples and real post-explosion solid debris
      samples and optimized using gas chromatography with an electron capture detector
      (GC-ECD) and high-performance liquid chromatography with ultraviolet detection
      (HPLC-UV). A modified SPME/HPLC interface utilizing dual six-port valves allowed
      for independent optimization of SPME desorption and injection variables that
      provided improved chromatographic resolution and sensitivity. A unique
      combination of cyano and octadecyl columns resulted in the complete separation of
      the 14 explosives in EPA method 8330 mixture using HPLC with good quantitative
      results. At the optimum SPME conditions, the limits of detection (LOD) were found
      to be of 5 ng/mL to 16 ng/mL of explosives in water and 10 microg/kg to 40
      microg/kg of explosives from soil. The technique has been successfully applied to
      the analysis of real post-explosion debris and can be adapted for use in the
      field utilizing portable chromatographic instruments.

PMID- 10914585
TI  - Application of true color X-ray vision for electron microscopy in fired bullets
      and gunshot residue investigation
AB  - An X-ray color imaging system was used to study primer particles and fired
      bullets from different .22 rimfire ammunition. The technique proved to be very
      useful, allowing a ready, concomitant analysis of the morphology of primer
      particles and their elemental composition. The investigation of the bottom of
      fired bullets showed that antimony present in the bullet alloy is not evenly
      distributed, but organized in plates made up of almost pure antimony. Moreover,
      particles and other traces adherent to lead bottomed bullets containing elements
      different from lead, therefore, useful to the understanding of primer composition
      are readily and easily detected.

PMID- 10914586
TI  - A density gradient technique for use in forensic soil analysis
AB  - A high-density aqueous salt solution for the preparation of density gradients is
      presented. It has been used successfully by the authors in forensic soil
      analysis. It has a density range that allows for the separation of a soil
      specimen's heavy mineral components. It has no odor or toxic fumes, which
      eliminates the need to use a hood during preparation, and is far superior to the
      organic liquids normally used to prepare density gradients. This liquid should
      cause many forensic scientists to reexamine their attitudes towards using density
      gradients in forensic soil casework.

PMID- 10914587
TI  - Obtaining fingerprints from mummified fingers: a method for tissue rehydration
      adapted from the archeological literature.
AB  - Our laboratory was asked to help with the rehydration of mummified human
      fingertips that had been removed from a recently deceased, unidentified female.
      Using a solution that was found in the archeological literature, we were able to
      successfully rehydrate dermal tissues to the extent that fingerprints could be
      taken. We believe that this solution, which until now has not been described in
      the forensic literature, is effective, affordable, and relatively easy to produce
      and use.

PMID- 10914588
TI  - A new infrared spectral library of controlled and noncontrolled drug standards
      using internal reflection spectroscopy.
AB  - An infrared spectral library containing 455 controlled and noncontrolled solid
      drug standards was generated using internal reflection spectroscopy. All
      attenuated total reflection (ATR) spectra were obtained with small diamond
      internal reflection elements. ATR spectra will have minor variations from
      transmission spectra commonly found in commercial infrared libraries.

PMID- 10914589
TI  - Normalization of residual ions after removal of the base peak in electron impact
      mass spectrometry
AB  - The mass spectra of compounds that produce limited detail under electron impact
      conditions may yield useful data for identification purposes when further
      examined. Through the mathematical removal of the base peak, previously
      noninformative ions become discriminating and useful for identification. In this
      work we show that this process of base peak removal and the re-normalizing of the
      remaining ions is reproducible under a variety of conditions and can be valuable
      for compound identification.

PMID- 10914590
TI  - A novel approach to obtaining reliable PCR results from luminol treated
      bloodstains.
AB  - In recent years the forensic scientist has been afforded great advances in
      technology both in the detection of latent bloodstains and in acquiring reliable
      DNA typing results from very small pieces of physical evidence. Scientists are
      now able to detect minute quantities of latent bloodstains by utilizing the
      luminol reagent, oftentimes indicating that an attempt has been made to conceal
      any evidence of bloodshed. With the introduction of PCR based technology to the
      forensic arena, scientists are now routinely able to obtain DNA typing results
      from previously insufficient amounts of biological material, items as small as a
      single hair, saliva on a cigarette butt, or a bloodstain the size of a pin head.
      We present here a merging of these two advances coupled with a new collection
      medium for post luminol treated latent bloodstains. The forensic scientist is now
      able to routinely isolate and recover an adequate amount of DNA suitable for PCR
      typing at all of the Promega GenePrint PowerPlex 1.1 loci. In this study, several
      dilutions of latent bloodstains were prepared in an effort to simulate
      transferred bloodstains that are routinely encountered in a crime scene setting.
      The latent bloodstains were treated with luminol and subsequently collected using
      conventional cotton tipped swabs as well as a Puritan sponge tipped swab. PCR
      typing at the Promega GenePrint PowerPlex 1.1 loci was then attempted upon all
      dilutions of the latent bloodstains for both collection mediums. The results
      clearly indicate that it is now routinely possible to recover adequate amounts of
      DNA suitable for PCR typing upon post luminol treated bloodstains.

PMID- 10914591
TI  - Allelic distribution of four tetranucleotide repeat loci (D3S1358, D18S51,
      D19S253, and FGA) in a population from Porto (North Portugal).
AB  - Allele frequencies for four short tandem repeat loci were determined in a
      population sample from Porto (North Portugal), using the polymerase chain
      reaction (PCR), in order to investigate possible genetic differences between
      populations from the center and north of Portugal. After denaturing PAGE
      electrophoresis, nine alleles were identified for D3S1358 (n = 256), 13 alleles
      for D18S51 (n = 235), 10 alleles for D19S253 (n = 238), and 15 alleles for FGA (n
      = 181). No deviations from Hardy-Weinberg equilibrium were found. The allele
      frequencies observed are similar to those of the Portuguese population compared
      except for the D3S1358 system.

PMID- 10914592
TI  - The analysis of three short tandem repeat (STR) loci in the Slovene population by
      multiplex PCR.
AB  - Allele frequencies for three tetrameric short tandem repeat (STR) loci D3S1358,
      HUMVWA, and HUMFGA were determined in a Slovene Caucasian population sample. DNA
      samples from a total of 221 Slovenes were amplified by multiplex PCR using the
      commercial kit AmpFISTR Blue (Perkin-Elmer). Separation and detection of the
      amplified STR fragments were carried out using a 377 automated genetic analyzer
      (Applied Biosystem Division/Perkin Elmer). Seven alleles at the D3S1358 locus, 8
      alleles at the HUMVWA31A locus, and 13 alleles at the HUMFGA locus were observed.
      A deviation from Hardy-Weinberg equilibrium was observed, only at the HUMVWA31A
      locus (p = 0.045, exact test). The departure at this locus was not significant
      after Bonferroni correction. There were no detectable departures between pairwise
      comparisons of the loci. The combined power of discrimination for all three loci
      is 0.9998, and the power of exclusion is 0.9526. The observed allele frequencies
      for the loci D3S1358, HUMVWA31A, and HUMFGA are similar to those in European and
      U.S. Caucasian populations.

PMID- 10914593
TI  - Chrysomya rufifacies (Macquart) (Diptera: Calliphoridae) established in the
      vicinity of Knoxville, Tennessee, USA.
AB  - The hairy maggot blow fly, Chrsomya rufifacies (Macquart) (Diptera:
      Calliphoridae) was collected in large numbers as both adults and immatures in the
      Knoxville, Tennessee, area during 1998 and is likely established there. The
      distribution of this species in the Old World, isothermal data, and its
      collection from mid-Michigan during 1998 suggest that it will eventually occupy
      most of the U.S. The forensic importance of C. rufifacies makes it probable that
      it will factor into an increasing number of medicolegal cases, but the expanding
      distribution of this species decreases its utility as a geographic indicator when
      postmortem movement of decedents is suspected.

PMID- 10914594
TI  - Formation of an interfering substance, 3,4-dimethyl-5-phenyl-1,3-oxazolidine,
      during a pseudoephedrine urinalysis.
AB  - During fatal aviation accident investigations, biosamples from the victims are
      submitted to the FAA Civil Aeromedical Institute (CAMI) for drug analysis. In the
      process of one such analysis by CAMI, an unknown substance was found in a urine
      sample. Simultaneous screening by thin layer chromatography (TLC) and gas
      chromatography/FID (GC/FID) suggested the presence of pseudoephedrine. A
      subsequent routine confirmation analysis of a separate urine aliquot by GC
      Fourier transform infrared (GC/FTIR) and GC mass spectrometry (GC/MS) indicated
      that the retention times of the unknown substance matched with those of
      pseudoephedrine. However, its infrared and mass spectra were different--the -OH
      and -NH groups were missing, a C-O-C group was present, and the molar mass was 12
      atomic mass units (amu) more than that of pseudoephedrine. A subsequent
      literature search suggested that ephedrine-like amines react with aldehydes to
      form oxazolidines. Therefore, the 12-amu increase could be accounted for by
      condensation of pseudoephedrine with formaldehyde. Since this aldehyde is present
      in various grades of methanol and ethyl acetate, and these solvents were used
      during the solid-phase extraction, 3,4-dimethyl-5-phenyl-1,3-oxazolidine was
      synthesized by using (+)-pseudoephedrine HCl and formaldehyde. The analytical
      findings of the synthesized compound were consistent with those of the unknown
      interfering substance, confirming that it was the oxazolidine. Aldehyde
      contaminants in solvents or specimens can transform drugs of interest and may
      result in misidentification of a compound originally present in specimens.
      Therefore, chemicals used in analyses should be of the highest available purity,
      and a multi-analytical approach should be adopted to maintain a high degree of
      quality assurance.

PMID- 10914595
TI  - DNA typing of samples for polymarker, DQA1, and nine STR loci from a human body
      exhumed after 27 years.
AB  - A body was exhumed from the ground after 27 years. Samples of femur bone, tooth,
      and a fingernail were collected and successfully subjected to DNA extraction,
      quantitation, amplification, and subsequently typed for DQA1, polymarker, and
      nine STR loci. All three types of samples were typed for D3S1358, vWA, FGA,
      D8S1179, D21S11, D18S51, D5S818, D13S17, D7S820, and amelogenin using ABI Prism
      377 DNA sequencer.

PMID- 10914597
TI  - Work-place homicide by bow and arrow.
AB  - Arrow wounds represent an unusual class of wounds rarely seen by most forensic
      pathologists. In this paper we present a case of homicide by bow and arrow and
      the characteristics of such injuries. The essential characteristics of the
      lesions obtained from conically-tapered field points and from hunting broadhead
      tips are described and discussed in relation to injuries caused by firearm
      bullets. In the present case, three arrows struck the victim, and the order in
      which the injuries were sustained are analyzed. We also discuss the possibilities
      of localizing the shooter relative to the victim by analysis of the trajectories.

PMID- 10914596
TI  - The Frye hearing in Florida: an attempt to exclude scientific evidence.
AB  - State Supreme Courts require a minimum threshold of reliability and acceptance in
      the scientific community for all medical and similar evidence to be admitted at
      trial. In Florida and some other states, the courts adhere to what is known as
      the Frye standard, whereas in most states and in Federal Courts, it is the so
      called Daubert standard. The jurisdiction of the present case is Hillsborough
      County (Tampa), Florida. Forensic pathologists seldom, if ever, are requested to
      participate in such hearings, unlike their toxicological and basic science
      colleagues who are more involved in research methodology and technical
      procedures. The burden is on the proponent of the evidence to prove the general
      acceptance of both the underlying scientific principle of the test and procedures
      used to apply that principle to the facts of the case at hand. The trial judge
      has the sole discretion to determine this question and general acceptance must be
      established by a preponderance of the evidence. The authors describe in detail a
      hearing in a case in which they were all involved. One author (WQS) had
      researched and documented the original scientific methodology in the literature.
      The situation involved a car and tractor trailer crash with the two occupants of
      the car dying of multiple trauma, whereas the truck driver was not injured.
      Autopsy of the auto driver revealed multiple injuries with exsanguination, and
      only vitreous humor and liver tissue, but not blood, were tested for ethyl
      alcohol. The estate of the driver of the automobile brought suit against the
      owner of the trucking company for wrongful death. The plaintiff requested a Frye
      hearing to question the reliability of testing other body specimens to translate
      to probable blood alcohol level. The testimony, submitted documents, and eventual
      decision by the judge are discussed.

PMID- 10914598
TI  - Motorboat propeller injuries.
AB  - The authors analyze the case of an Albanian refugee who was killed by the
      propellers of the outboard engine of a rubber dinghy while illegally attempting
      to reach Italy. The finding of multiple parallel, deep clear-cut injuries is
      uncommon, but highly characteristic of the object producing the lesions. These
      are typical and cannot be mistaken with those produced by sharp objects or shark
      bites. The description of the injuries is vital for establishing the position of
      the victim with regard to the propeller that struck him.

PMID- 10914599
TI  - Unexpected sudden death from coronary sinus thrombosis. An unusual complication
      of central venous catheterization.
AB  - Coronary sinus thrombosis is an unusual but potentially serious complication of
      the use of central venous devices. We report a fatal case of coronary sinus
      thrombosis in relation to a malpositioned central venous catheter. The death
      occurred very soon following the beginning of symptoms and the cause could not be
      suspected. Direct trauma of the catheter on the coronary sinus endothelium seems
      the most probable cause of the thrombosis.

PMID- 10914600
TI  - Unusual cases of suicide among health care workers.
AB  - We describe three unusual cases of suicide committed by health care workers. The
      aim of this paper was to analyze and evaluate the evidence of general diagnostic
      elements of poisoning in these cases.

PMID- 10914602
TI  - Development of the X-linked tetrameric microsatellite marker DXS9898 for forensic
      purposes.
AB  - HumDXS9898 also known as CHLC x GATA 126G01 is a tetrameric microsatellite marker
      located at the Xq21.33 pericentromeric region. In kinship testing HumDXS9898 is
      suitable for concomitant use with HumHPRTB and HumDXS6807 which are separated
      from HumDXS9898 by genetic map distance of 150 and 80 cM, respectively.
      HumDXS9898 is closely linked to HumARA. In the German population, HumDXS9898
      exhibits seven clearly distinguishable alleles ranging from 189 to 214 basepairs
      in size. Deviation from Hardy-Weinberg equilibrium could not be detected. The
      observed heterozygosity was 0.75 for females and the mean exclusion probability
      was 0.73 for female children. Mutations were not found in the present material.

PMID- 10914601
TI  - A mixed-drug intoxication involving venlafaxine and verapamil.
AB  - This case report describes the suicide of a 52-year-old woman whose cause of
      death was attributed to a mixed-drug intoxication involving venlafaxine and
      verapamil. Venlafaxine is prescribed for the treatment of depression and should
      be used with caution in patients with cardiovascular disease. Verapamil is a
      calcium channel blocker primarily used for treatment of cardiovascular disorders.
      The following drug concentrations were determined in postmortem fluids: verapamil
      -3.5 mg/L (femoral blood), 9.4 mg/L (subclavian blood), and 1.0 mg/L (vitreous
      fluid); norverapamil--1.0 mg/L (femoral blood), 2.1 mg/L (subclavian blood), and
      0.20 mg/L (vitreous fluid); verapamil and norverapamil could not be detected in
      bile or urine due to the high levels of erythromycin present; venlafaxine--6.2
      mg/L (femoral blood), 8.6 mg/L (subclavian blood), 5.3 mg/L (vitreous fluid),
      54.0 mg/L (bile), and 72.3 mg/L (urine); and O-desmethylvenlafaxine--5.4 mg/L
      (femoral blood), 8.3 mg/L (subclavian blood), positive (vitreous fluid), 29.2
      mg/L (bile), and 9.5 mg/L (urine). The cause of death was determined to be a
      mixed-drug intoxication resulting from an overdose of verapamil and venlafaxine.
      The manner of death was determined to be suicide.

PMID- 10914603
TI  - Sequence variation of new alleles at the short tandem repeat D19S253 locus.
AB  - This paper reports the sequences of two new alleles identified in a population
      database study on the short tandem repeat D19S253 locus. A Portuguese Caucasian
      population and a Portuguese African population were studied. Forty-four selected
      alleles were sequenced and 11 different alleles were found. All the sequenced
      alleles shown to possess a simple tetranucleotide GATA repeat region structure.
      The two new alleles, alleles 6 and 16, follow the simple repeat pattern. During
      paternity investigation casework, 1028 meiosis were analyzed and five isolated
      genetic incompatibilities detected. In one case, a non-detectable allele with the
      used set of primers could be the explanation. In the other four cases, single
      step mutations could be considered. The mutation rate obtained for this locus was
      3.89 x 10(-3).

PMID- 10914604
TI  - The first mail bomb?
AB  - A news item in the newspaper, the Evening Star, for the Country, October 18,
      1833, probably is the first report of a mail bomb in the United States. It is
      also likely to be the first defusing of a mail bomb. The device appeared to be
      extraordinarily sophisticated and would have likely worked had it not been for
      suspicions of the recipient of the bomb.

PMID- 10914605
TI  - Allele frequencies for the CODIS core STR loci in Connecticut populations.

PMID- 10914606
TI  - Allele frequency distributions for twelve STR loci in a Brazilian population.

PMID- 10914607
TI  - HLA-DQA1 and polymarker locus allele frequencies for Elazig/Turkey.

PMID- 10914608
TI  - Distribution of HumvWA31, HumFESFPS, HumTH01, HumTPOX, HumCD4, HumCSF1PO alleles
      in a Southern Italian population sample.

PMID- 10914609
TI  - Distribution of D1S80 and HLA-DQA1 alleles in a Southern Italian population
      sample.

PMID- 10914610
TI  - Allele frequencies for the COFILER STR loci in the Canadian Caucasian and
      Canadian First Nations populations.

PMID- 10914611
TI  - Allele frequencies for the COFILER STR loci in the Canadian Caucasian and
      Canadian First Nations populations.

PMID- 10914612
TI  - Soy phytoestrogens: an adjunct to hormone replacement therapy?

PMID- 10914613
TI  - Phytoestrogens: alternative or complementary?

PMID- 10914614
TI  - The role of isoflavones in menopausal health: consensus opinion of The North
      American Menopause Society.
AB  - OBJECTIVE: Given the increasing interest in the effect of isoflavones on
      menopause-related symptoms and diseases related to menopause/aging combined with
      the growing body of published literature on isoflavones, much of which presents
      conflicting data, The North American Menopause Society (NAMS) established a goal
      to develop an evidence-based consensus opinion on the role of isoflavones in
      menopausal health. DESIGN: NAMS appointed a panel of clinicians and researchers
      acknowledged to be experts in the field of isoflavones. Their advice was used to
      assist the NAMS Board of Trustees in developing this consensus opinion. RESULTS:
      Many animal and human studies have evaluated the health effects of isoflavones on
      menopause-related symptoms and diseases related to menopause/aging. However, data
      are inconclusive regarding whether the observed health effects in humans are
      attributable to isoflavones alone or to isoflavones plus other components in
      whole foods. The most convincing health effects have been attributed to the
      actions of isoflavones on lipids. Studies have associated isoflavones with
      statistically significant reductions in low-density lipoproteins and
      triglycerides as well as increases in high-density lipoproteins. Although some
      data seem to support the efficacy of isoflavones in reducing the incidence and
      severity of hot flashes, many studies have not found any difference between the
      isoflavone recipients and the controls. Inadequate data exist to evaluate the
      effect of isoflavones on breast and other female-related cancers, bone mass, and
      vaginal dryness. CONCLUSIONS: Although the observed health effects in humans
      cannot be clearly attributed to isoflavones alone, it is clear that foods or
      supplements that contain isoflavones have some physiologic effects. Clinicians
      may wish to recommend that menopausal women consume whole foods that contain
      isoflavones, especially for the cardiovascular benefits of these foods; however,
      a level of caution needs to be observed in making these recommendations.
      Additional clinical trials are needed before specific recommendations can be made
      regarding increased consumption of foods or supplements that contain high amounts
      of isoflavones.

PMID- 10914615
TI  - Soy phytoestrogens improve radial arm maze performance in ovariectomized retired
      breeder rats and do not attenuate benefits of 17beta-estradiol treatment.
AB  - OBJECTIVE: Soy phytoestrogens (SPEs) seem to have beneficial effects on the
      cardiovascular system with no adverse effects on the breast and uterus. Our
      objective was to examine the effects of oral estradiol alone, soy protein with
      phytoestrogens alone, and combinations of estradiol and SPEs on working memory of
      ovariectomized retired breeder female rats using the radial arm maze test.
      DESIGN: Eighty-four bilaterally ovariectomized retired breeder female rats were
      randomized into 12 groups to examine the effects of chronic treatment (10 months)
      with oral micronized estradiol (0, 0.5, 1, and 2 mg/1,800 Cal), SPEs (0, 72, and
      144 mg/1,800 Cal), and all combinations of these doses of estradiol and SPEs on
      working memory. RESULTS: Oral administration of estradiol or SPEs resulted in a
      dose-dependent improvement in the performance of the radial arm maze tests. In
      addition, at each of the three doses of oral micronized estradiol tested, the
      performance of the radial arm tests was not significantly different in the
      presence or absence of SPEs. CONCLUSIONS: Our data suggest that SPEs may function
      as estrogen agonists in improving working memory in the ovariectomized retired
      breeder female rats and that SPEs do not antagonize the beneficial effects of
      estradiol on the working memory of these rats. No additional benefits on the
      radial arm maze test performance were observed with the tested combinations of
      estradiol and SPEs.

PMID- 10914616
TI  - Vasomotor symptom relief by soy isoflavone extract tablets in postmenopausal
      women: a multicenter, double-blind, randomized, placebo-controlled study.
AB  - OBJECTIVE: To determine the safety and efficacy of an oral soy isoflavone extract
      for relief of menopausal hot flushes. DESIGN: This was a double-blind,
      randomized, parallel group, outpatient, multicenter (15 sites) study. A total of
      177 postmenopausal women (mean age = 55 years) who were experiencing five or more
      hot flushes per day were randomized to receive either soy isoflavone extract
      (total of 50 mg genistin and daidzin per day) or placebo. Physical examinations
      and endometrial and biochemical evaluations were performed upon admission and
      completion. Body weight, symptoms, and safety were evaluated at all visits.
      RESULTS: Relief of vasomotor symptoms was observed in both groups. Decreases in
      the incidence and severity of hot flushes occurred as soon as 2 weeks in the soy
      group, whereas the placebo group experienced no relief for the first 4 weeks.
      Differences between evaluable subjects in both groups were statistically
      significant over 6 weeks (p = 0.03). Over 12 weeks, between-group differences
      approached significance (p = 0.08). Endometrial thickness evaluated by
      ultrasound, lipoproteins, bone markers, sex hormone-binding globulin and follicle
      stimulating hormone, and vaginal cytology did not change in either group.
      CONCLUSIONS: Soy isoflavone extract was effective in reducing frequency and
      severity of flushes and did not stimulate the endometrium. Soy isoflavone
      extracts provide an attractive addition to the choices available for relief of
      hot flushes.

PMID- 10914617
TI  - Serum estradiol-binding profiles in postmenopausal women undergoing three common
      estrogen replacement therapies: associations with sex hormone-binding globulin,
      estradiol, and estrone levels.
AB  - OBJECTIVE: To compare the effects of three commonly prescribed estrogen
      replacement therapies-oral conjugated equine estrogens (CEE; n = 37), oral
      micronized estradiol (ME; n = 25), and transdermal estradiol (TE; n = 24)-on the
      binding characteristics of plasma estradiol as related to the concentrations of
      blood sex hormone-binding globulin (SHBG), estradiol, and estrone. DESIGN:
      Menopausal volunteers, opting for estrogen replacement therapy, gave blood at 0,
      2, and 4 months. SHBG was assayed by automated immunoabsorbent technology.
      Estradiol and estrone were determined by quantitative gas chromatography/mass
      spectrometry. After tritiated estradiol was added to serum, the percentage of
      estradiol not bound to protein was determined by ultrafiltration and the
      percentage of estradiol bound to SHBG was measured by a method exploiting that
      this protein, even when bound to estradiol, binds avidly to Concanavalin A
      Agarose. RESULTS: In each study, 2- and 4-month data were similar. Increases in
      SHBG concentrations were 100% (p < 0.001), 45% (p < 0.001), and 12%
      (nonsignificant) for subjects who were receiving CEE, ME, and TE regimens,
      respectively. Decreases in the percentage of estradiol not bound to protein and
      increases in the percentage of estradiol bound to SHBG correlated with changes in
      the concentrations of this protein mediated by the therapies. The order for
      increases in estradiol was ME-TE >> CEE, whereas for estrone, the order was ME >
      CEE >> TE, divergent from the SHBG responses. CONCLUSIONS: The diverse responses
      observed can be explained by differences in the estrogen load delivered to target
      tissues as controlled by the intermediary circulation and metabolism of the
      hormones introduced in these regimens.

PMID- 10914618
TI  - Administration of testosterone undecanoate in postmenopausal women: effects on
      androgens, estradiol, and gonadotrophins.
AB  - OBJECTIVE: To investigate serum androgens, estradiol, and gonadotrophins after
      treatment with testosterone undecanoate 40 mg daily in postmenopausal women.
      DESIGN: Ten postmenopausal women received 40 mg testosterone undecanoate orally
      every day for 4 days. Blood samples were drawn before and 2, 4, 6, and 8 hours
      after administration on the first day and then at 24, 48, 72, and 96 hours after
      administration of the first dose. Serum concentrations of testosterone,
      dihydrotestosterone, androstenedione, estradiol, sex hormone-binding globulin,
      follicle-stimulating hormone, and luteinizing hormone were analyzed. RESULTS: A
      rapid absorption of testosterone undecanoate was found with the highest
      concentrations of testosterone, dihydrotestosterone, and androstenedione 2-4
      hours after administration. Significant increases from basal values were found
      for serum testosterone, dihydrotestosterone, androstenedione, and estradiol and a
      slight but significant decrease for sex hormone-binding globulin. Serum follicle
      stimulating and luteinizing hormone levels were unchanged. Median levels of 3.2
      nmol/L for testosterone and 3.6 nmol/L for dihydrotestosterone were recorded
      after the first day. CONCLUSIONS: Testosterone undecanoate displayed a rapid
      absorption and turnover and may offer an alternative for androgen treatment in
      women. Expanded pharmacokinetic studies in larger and more homogeneous groups of
      postmenopausal women should be performed. The individual variations were
      considerable, and regular monitoring of testosterone serum levels to avoid
      overtreatment is recommended.

PMID- 10914619
TI  - Memory functioning among midlife women: observations from the Seattle Midlife
      Women's Health Study.
AB  - OBJECTIVE: As the number of midlife women increases, there is an increased
      interest in women's experiences of the perimenopause. Because of the evidence
      linking estrogen with cholinergic and serotonergic activity in the brain and with
      central nervous system development of dendritic arborization, and mixed evidence
      of estrogen use with incidence of Alzheimer's disease, the effects of the
      perimenopause on memory functioning are of interest. The purpose of these
      analyses, part of the Seattle Midlife Women's Health Study, was to describe
      changes in women's perceived memory functioning according to their perimenopausal
      group, age, perceived stress, health status, and mood. DESIGN: Memory functioning
      was assessed with the Memory Functioning Questionnaire as part of a questionnaire
      mailed to study participants annually. Perimenopausal group was assessed using
      Mitchell's rating schema. RESULTS: Age was unrelated to any of the Memory
      Functioning Questionnaire indicators except for retrospective memory; younger
      women reported more memory problems than older women. Perimenopausal groups were
      unrelated to most memory functioning ratings with few exceptions. Memory
      functioning ratings of current memory compared with the past were worse for women
      who were in early and middle transition and for those who were using hormone
      therapy than for those who were in late transition and postmenopause. Women
      reported more current memory problems compared with 10 and 20 years ago and at
      age 18. Health ratings were negatively correlated with memory functioning
      ratings, and depressed mood positively correlated with nearly every indicator of
      memory functioning (frequency of memory problems, ratings of current memory, past
      memory, and memory change). Greater perceived stress levels were associated with
      more memory problems. CONCLUSIONS: Perceived memory functioning seems more
      closely related to perceived health, depressed mood, and perceived stress than to
      perimenopausal stage or age. Further work is needed to determine whether these
      ratings provided by the Seattle cohort will change over time as women age and as
      they make the transition to menopause and beyond.

PMID- 10914620
TI  - Patient knowledge about hormone replacement therapy: implications for treatment.
AB  - OBJECTIVE: To determine whether women's global self-assessment of their knowledge
      about hormone replacement therapy (HRT) corresponds to their performance on an
      explicit knowledge test about HRT and to measure associations among knowledge,
      personal characteristics, decision conflict, and intention to use HRT. DESIGN:
      Preintervention telephone survey of 156 women enrolled in a randomized, placebo
      controlled trial of HRT decision aids. RESULTS: The mean rating of menopause
      knowledge, on a scale from 1 to 10, with 10 indicating being "extremely
      knowledgeable," was 5.6 (range = 0-10) and of HRT was 4.2 (range = 0-9). The mean
      summary score for the explicit HRT knowledge test, on a 16-point scale, was 7.8
      (range = 0-15). After adjustment for demographic characteristics and exposure to
      a provider conversation, higher income, white race, and the provider discussion
      were significant correlates of knowledge. Explicit knowledge was positively
      correlated with self-assessed menopause knowledge and HRT knowledge (Spearman's
      correlation coefficient = 0.39 and 0.52, respectively; p < 0.0001). Greater
      knowledge was not associated with intention to use HRT 1 year later. Women who
      had greater knowledge reported less conflict about the HRT decision (Spearman's
      correlation coefficient = -0.32; p < 0.0001). CONCLUSIONS: A global question
      about level of knowledge is an effective clinical tool for identifying patients
      who are in need of additional education about HRT and menopause in this managed
      care population. Increased knowledge may decrease women's conflict about the HRT
      decision. Having had a previous conversation about menopause with a primary care
      provider is associated with greater knowledge about HRT.

PMID- 10914621
TI  - Important factors for use of hormone replacement therapy: a population-based
      study of Swedish women. The Women's Health in Lund Area (WHILA) Study.
AB  - OBJECTIVE: The aim of this study was to delineate the use of hormone replacement
      therapy (HRT) among women who were born between December 2, 1935, and December 1,
      1945, and living in the Lund area of southern Sweden and to analyze factors that
      contribute to the acceptance and continuation of HRT. METHODS: All women received
      a generic questionnaire pertaining to demographic background, lifestyle, health
      behavior, and climacteric symptoms and underwent a personal interview. An interim
      analysis was carried out on 3,900 women. We mailed a hormone questionnaire to the
      women who were using HRT (n = 1,875). This hormone questionnaire covered, for
      example, menopausal status, complaints, and alterations in and efficacy of HRT
      use, as well as the reasons for discontinuing HRT use. RESULTS: A total of 1,415
      (76%) women answered the hormone questionnaire. Forty-eight percent were HRT ever
      users, and 32% were current users. Mean duration of HRT use was 47 months. The
      most common incentives for HRT use were alleviation of menopausal symptoms (72%)
      and prevention of bone loss (50%) and/or cardiovascular disease (31%). Forty
      seven percent of HRT users reported that they had changed regimens at least once.
      HRT users had higher education, full-time work, and a higher consumption of
      alcohol but less consumption of cigarettes. They reported higher frequencies of
      climacteric symptoms, past histories of premenstrual syndrome, use of oral
      contraceptives, and hysterectomy. They also had a higher consumption of
      healthcare resources. A total of 177 women withdrew from therapy. The most common
      reasons for discontinuation of HRT were weight gain, anxiety of cancer, bleeding,
      breast tenderness, and emotional problems. Compared with current users, past
      users had less positive as well as fewer negative effects of HRT. Several
      variables contributed to compliance, including education, full-time work, regular
      exercise, low frequency of persistent climacteric symptoms, and alteration of
      regimens. CONCLUSION: Education, working conditions, lifestyle, interest in
      prevention, and severity of the climacteric symptoms are determinants for both
      acceptance of and compliance with HRT.

PMID- 10914622
TI  - Neonatal transverse cerebellar diameter in normal and growth-restricted infants.
AB  - OBJECTIVE: To assess the transverse cerebellar diameter (TCD) in preterm and term
      neonates with normal growth or growth restriction. METHODS: TCD was
      sonographically measured after birth in 404 neonates born between 23 and 42 weeks
      of gestation. The study included two groups: Group 1: 334 appropriately grown for
      gestational age (AGA) neonates (both birthweight (BW) and head circumference (HC)
      were between the 3rd and 97th centiles), which were subdivided into two subgroups
      according to the HC measurements. Group 2: 70 small for gestational age (SGA)
      neonates (BW <3rd centile), were further divided into three subgroups according
      to HC measurements. RESULTS: In Group 1 of AGA neonates, a linear growth function
      was observed between the TCD and GA (R = 0.914, P < 0.00001, TCD = 0.279 + 0.142
      X GA), and between TCD and HC (R = 0.886, P < 0.00001, TCD = -0.333 + 1.777 X
      HC). The percentage of neonates with normal TCD (> or =10th centile) was more
      than 85% of the AGA and asymmetric SGA subgroups, and 60.7% of the microcephalic
      SGA subgroup (P < 0.02). CONCLUSIONS: This study provides normative data of
      neonatal TCD across gestational age. TCD measurement via sonography is a new
      adjunctive criterion for objectively assessing gestational age in infants when a
      precise determination of gestational age is necessary. This is very important
      since utility of the TCD is effective for both AGA and asymmetric SGA infants.

PMID- 10914623
TI  - Unexplained elevated midtrimester maternal serum levels of alpha fetoprotein,
      human chorionic gonadotropin, or low unconjugated estriol: recurrence risk and
      association with adverse perinatal outcome.
AB  - OBJECTIVE: To determine if women experiencing an unexplained elevated maternal
      serum alpha fetoprotein (MSAFP; > or =2.0 MoM) or human chorionic gonadotropin
      (hCG; > or =2.0 MoM), or low unconjugated estriol (E3; < or =0.5 MoM) in one
      pregnancy are at increased risk for similar results in a subsequent pregnancy,
      and to determine if recurrence of these analyte extremes is associated with
      adverse perinatal outcome. METHODS: We identified all women delivering two
      consecutive singleton pregnancies at one hospital between 1992-1997 for whom
      second trimester trisomy 21 serum screen was performed in each pregnancy. All
      screens were performed in a single laboratory. Each pregnancy delivered after 20
      weeks and had gestational age confirmed by ultrasound prior to 24 weeks. Subjects
      were excluded if a fetal anomaly or aneuploidy was present. Adverse outcomes
      included abruption, oligohydramnios, preeclampsia, preterm membrane rupture,
      preterm delivery, stillbirth, birthweight <10th centile, and admission to
      neonatal intensive care unit (NICU). RESULTS: A total of 538 women had 1,076
      pregnancies meeting inclusion criteria; 12/515 (2.3%) of women with a normal
      MSAFP, 28/470 (6.0%) with a normal hCG, and 11/504 (2.2%) with a normal E3 in the
      first pregnancy had an anomalous result for the respective analyte in the second
      pregnancy. In contrast, only 4/23 (17.4%) patients with an elevated MSAFP (P =
      0.003), 14/44 (31.8%) with an elevated hCG (P < 0.001), and 2/10 (20.0%) with a
      low E3 (P < 0.025) in the first pregnancy had the same analyte anomaly recur in
      the second pregnancy. The odds ratios for recurrent elevated MSAFP, hCG, and low
      E3 were 7.5, 5.3, and 9.2, respectively. Adverse perinatal outcomes occurred with
      similar frequency, regardless of MSAFP, hCG, or E3 results in consecutive
      pregnancies, using women with normal MSAFP, hCG, and E3 results in one or both
      pregnancies as controls. CONCLUSIONS: Women experiencing an anomalous serum
      analyte in one pregnancy are at significant risk to experience the same analyte
      result in a subsequent pregnancy.

PMID- 10914624
TI  - Elevated maternal serum alpha-fetoprotein with low unconjugated estriol and the
      risk for lethal perinatal outcome.
AB  - OBJECTIVE: To determine whether a combination of elevated maternal serum alpha
      fetoprotein (MSAFP) and low unconjugated estriol (E3) concentration identifies
      pregnancies at particularly high risk for fetal abnormality or poor outcome.
      METHODS: Pregnancy outcomes were reviewed for women with elevated MSAFP (> or
      =2.0 MoM) from our database of 50,315 women who had received triple marker
      testing from 1993-1998. Outcomes for those with low E3 (< or =0.7 MoM) were
      compared with those with normal E3 (>0.7 MoM). The incidences of fetal death,
      neural tube defects, chromosome abnormalities, congenital abnormalities, preterm
      birth, small-for-gestational age (SGA), twins, and inaccurate dates were compared
      in the two groups using Fisher's exact test with P < 0.05 considered significant.
      RESULTS: Of the 50,315 women screened, 1,435 (2.85%) had an elevated MSAFP.
      Pregnancy outcomes were obtained in 94% of those with elevated MSAFP and 70% of
      all patients screened. Neural tube defects were present in 57 fetuses/infants (21
      anencephalic, 29 spina bifida, 7 encephalocele) of which 46 (81%) had an elevated
      MSAFP. Of the 1,435 women with an elevated MSAFP, 199 (14%) had a low E3.
      Compared to those women with elevated MSAFP but normal E3, women with elevated
      MSAFP and low E3 were at significantly increased risk for fetal death (20.6% vs.
      2.8%, relative risk (RR) 8.9), anencephaly (9.0% vs. 0.1%, RR 122.8) and
      chromosome abnormality (2.5% vs. 0.6%, RR 4.0). CONCLUSIONS: Pregnancies
      complicated by elevated second trimester MSAFP and low E3 are at a particularly
      high risk (32%) for lethal perinatal outcomes. Twins, while a common cause of
      elevated MSAFP, are rarely found when an elevated MSAFP is associated with low
      E3.

PMID- 10914625
TI  - Nonobstetrical abdominal surgery during pregnancy in Women's Hospital.
AB  - OBJECTIVE: To determine if nonobstetrical abdominal surgery during pregnancy in
      Women's Hospital at the University of Southern California School of Medicine was
      associated with increased rates of preterm delivery or spontaneous loss.
      Preoperative diagnostic accuracy was also evaluated. METHODS: We performed a
      retrospective review of all cases of nonobstetrical abdominal surgery in our
      institution during a 7-year period from November 1991 to November 1998. RESULTS:
      One hundred-six cases of nonobstetrical abdominal surgery were identified. Eighty
      eight women underwent laparotomy and 18 had laparoscopic abdominal surgery.
      Seventy-three women had emergent surgery and 31 had elective surgery. Seventy-six
      percent (80/106) of subjects had the same preoperative and postoperative
      diagnoses. We obtained delivery data for 62 of 106 (59%) subjects. Eleven of 62
      (18%) subjects who had nonobstetrical abdominal surgery during pregnancy
      delivered preterm (<37 weeks' gestation). This was not significantly different
      from the institutional preterm delivery rate of Women's Hospital (8999/56305
      [16%]) (P = 0.84). Two of 106 (2%) women experienced spontaneous pregnancy loss
      following surgery; both occurred in the second trimester. CONCLUSIONS:
      Nonobstetrical abdominal surgery during pregnancy in Women's Hospital was not
      associated with higher frequencies of preterm deliveries or spontaneous losses
      than our institutional rates.

PMID- 10914626
TI  - Levels of stable metabolites of prostacyclin and thromboxane A2 and their ratio
      in normotensive and preeclamptic pregnant women during the antepartum and
      postpartum periods.
AB  - OBJECTIVE: To measure the levels of the circulating metabolites of prostacyclin
      and thromboxane A2 during the antepartum and postpartum periods in severe
      preeclamptic and eclamptic patients as well as in normotensive pregnant women.
      METHODS: 6-Keto-prostaglandin F1alpha (6-keto-PGF1alpha) and thromboxane B2
      (TxB2) were measured in the plasma of 15 severe preeclamptic, 15 eclamptic, and
      15 normotensive pregnant women during the antepartum and postpartum (5th day)
      periods. At the same time blood pressure measurements were obtained. Kruskal
      Wallis, Wilcoxon rank-sum, and Wilcoxon's signed-rank tests were used for
      statistical analysis. RESULTS: 1) There was no significant difference in the
      levels of 6-keto-PGF1alpha and TxB2 of the normotensive pregnant women between
      the antepartum and the postpartum (5th day) periods. 2) In the severe
      preeclamptic and eclamptic groups, 6-keto-PGF1alpha levels showed significant
      increase after the delivery (P < 0.01, and P < 0.001, respectively). 3) In the
      severe preeclamptic and eclamptic groups TxB2 levels showed significant decrease
      after delivery (P < 0.01, and P < 0.001, respectively). 4) The 6-keto
      PGF1alpha/TxB2 ratio both during the antepartum and the postpartum (5th day)
      periods showed significant differences between the severe preeclamptic and
      normotensive, and between the eclamptic and normotensive groups (P < 0.001, and P
      < 0.001 respectively). 5) No correlation was observed between the mean arterial
      pressure and the antepartum levels of 6-keto-PGF1alpha TxB2 or their ratios.
      CONCLUSIONS: Our study was able to demonstrate a significant difference in
      circulating metabolites of prostacyclin and TxA2 between normotensive pregnant
      women and those with severe preeclampsia and eclampsia. But no correlation was
      observed between the blood pressure and the antepartum 6-keto-PGF1alpha, TxB2
      levels or their ratios. 6-keto-PGF1alpha levels increased and TxB2 levels
      decreased in the postpartum period (5th day). However, the 6-keto-PGF1alpha/TxB2
      ratio was still low in the severe preeclamptic and eclamptic patients when
      compared with the control group. This situation shows that the pathophysiologic
      mechanism does not improve completely within a few days after delivery.

PMID- 10914627
TI  - Placental laterality may be a random event and not the result of inherent uterine
      artery pathology.
AB  - OBJECTIVE: To determine whether placental laterality and discordant uterine
      artery impedance during pregnancy is a random event or the result of uterine
      artery pathology. METHODS: We identified 50 patients with unilateral placenta and
      pathologic uterine artery impedance during their current pregnancy and enrolled
      them in the study. Thirty-three of these patients met the inclusion criteria and
      returned during the first 10 days of their third normal menstrual cycle after
      delivery. We examined the pelvic anatomy to rule out any pelvic pathology and
      then used color and pulsed wave duplex Doppler to identify the uterine artery in
      the immediate vicinity of the paracervical area at the level of the isthmus. We
      obtained the uterine artery resistance index (RI) from each uterine artery. We
      performed statistical analysis by means of t-test. RESULTS: The uterine artery
      ipsilateral to the placenta exhibited significantly lower impedance than the
      contralateral in the pregnant state. When the placenta was right, the values
      (mean +/- SD) were 0.60 +/- 0.11 vs. 0.73 +/- 0.09 for the right and left artery,
      respectively. When the placenta was left the values were 0.57 +/- 0.08 vs. 0.77
      +/- 0.07 for the left and right uterine artery, respectively. In the nonpregnant
      state, the corresponding values were 0.90 +/- 0.04 vs. 0.90 +/- 0.05 and 0.91 +/-
      0.05 vs. 0.90 +/- 0.04, respectively. CONCLUSION: In patients with a unilateral
      placenta and discordant pathological uterine artery impedance during pregnancy,
      there is no evidence of discordant impedance between the two uterine arteries in
      the postpartum period. We speculate that the location of placental implantation
      may not be the result of preexisting uterine artery discordant impedance.

PMID- 10914628
TI  - Analysis of antepartum fetal heart rate tracing by physician and computer.
AB  - OBJECTIVE: To compare the interpretation of fetal heart rate (FHR) tracings by
      three obstetricians with that of a computer analysis program. METHODS: Our study
      population consisted of high-risk pregnant women referred as outpatients for
      antepartum FHR monitoring. A total of 121 FHR tracings, from a series of 54
      consecutive women, were interpreted by three physicians and a computer program
      (Oxford Sonicaid System 8000, Oxford Sonicaid Ltd., Chichester, UK). The
      physicians used a modified FHR scoring system to interpret the tracings. Total
      scores were categorized as 0-4: abnormal, 5-7: questionable, and 8-10: normal.
      The computer program used overall variation, categorized as normal: longer than
      30 ms, abnormal: shorter than 20 ms, and questionable: 20-30 ms. RESULTS:
      Significant differences were found among the physicians and between the
      physicians and the computer analysis for the individual elements of FHR tracings.
      There was very good agreement between two physicians and the computer in the
      assessment of the FHR baseline. When physicians used a FHR scoring system to
      classify the tracings as normal, questionable, or abnormal, the agreement was
      poor (kappa values ranged from -0.037 to 0.28). The computerized analysis
      identified two FHR tracings as questionable but both were classified as normal by
      all three physicians. CONCLUSIONS: The level of agreement in the interpretation
      of FHR tracings was poor among physicians and between physicians and the computer
      analysis. A FHR scoring system did not improve the level of agreement between
      physicians.

PMID- 10914629
TI  - Prenatal magnetic resonance imaging assisting in differentiating between large
      degenerating intramural leiomyoma and complex adnexal mass during pregnancy.
AB  - We present an unusual case in which a 36-year-old patient was referred due to
      increasing upper left quadrant abdominal pain and a possible left adnexal mass at
      22 weeks' gestation. Ultrasonography demonstrated a multiseptated cystic mass,
      with solid components measuring 12 cm in diameter. A thin sonolucency was thought
      to separate the mass from the uterus and thus the mass was considered consistent
      with an adnexal mass, possibly a mucinous cystadenoma. A large degenerating
      leiomyoma could not be ruled out with certainty and magnetic resonance (MR)
      imaging was performed which depicted a thin band of myometrium encompassing the
      complex mass and was therefore diagnostic of a degenerating uterine leiomyoma. We
      discuss the contribution of MR imaging in the noninvasive diagnosis of
      undetermined solid pelvic masses visualized ultrasonographically.

PMID- 10914630
TI  - Familial pyloric atresia: report of a family and review of the literature.
AB  - Pyloric atresia occurs in one in a million births and usually occurs
      sporadically. We report a family with nine affected members and review the
      literature for all reported familial cases. The article stresses the possibility
      of recurrence of pyloric atresia in the progeny of consanguinous parents, with an
      emphasis on prenatal diagnosis and counseling, diagnosis of the entity in
      neonates, associated conditions, and prognosis in sporadic and familial cases. A
      high index of suspicion in affected families contributes to the early diagnosis
      and treatment with a great impact on outcome.

PMID- 10914631
TI  - Surgical treatment of uterine atony employing the B-Lynch technique.
AB  - Postpartum hemorrhage remains a major cause of maternal morbidity and mortality.
      Four cases utilizing the B-Lynch technique for control of hemorrhage secondary to
      uterine atony are presented. The B-Lynch technique appears to be effective in
      controlling postpartum hemorrhage. More experience is needed before the B-Lynch
      technique can be accepted as routine practice.

PMID- 10914632
TI  - Vascular beta-adrenoceptor function in hypertension and in ageing.
AB  - Functional beta-adrenoceptors (beta-AR) have been identified and characterized in
      blood vessels under in vivo conditions as well as in vascular smooth muscle cells
      (SMC) grown in culture. Agonist occupancy of beta-AR activates adenylyl cyclase
      (AC) via the stimulatory guanine nucleotide-binding protein (Gs) and leads to
      elevations in intracellular adenosine 3'5'-cyclic monophosphate levels (cAMP).
      Increased cAMP activates the cAMP-dependent protein kinase (PKA), with subsequent
      phosphorylation of various target proteins. This beta-AR pathway interacts with
      several other intracellular signalling pathways via cross-talk, so that
      activation by beta-AR agonists may also modulate other second messengers and
      protein kinases. SMC beta-AR play an important role in SMC function. In intact
      blood vessels they mediate SMC relaxation by various intracellular mechanisms,
      ultimately causing a decrease in intracellular Ca2+ levels. In cultured SMC,
      activation of the beta-AR pathway results in inhibition of cellular
      proliferation, the development of SMC polyploidy, and SMC apoptosis. Blood
      vessels from hypertensive animals are characterized by an increase in SMC cell
      mass, a greater incidence of SMC polyploidy in the aorta, and an impairment in
      the beta-agonist-mediated SMC relaxation. Some of these changes may result from
      an attenuation of beta-AR function due to agonist-induced receptor
      desensitization caused by the uncoupling of receptors from the Gs-AC system. The
      phosphorylated beta-AR may in turn trigger new signals and activate different
      intracellular pathways. However, the details of these mechanisms are still
      unresolved. Since functional beta-AR play such a prominent and multi-faceted role
      in SMC function, it is important to understand how these diverse physiological
      effects are mediated by this receptor system, and how they contribute to the
      development of hypertension. With ageing, a decrease in beta-AR-Gs-AC coupling is
      observed, and this is implicated in the reduced responsiveness of SMC. The
      similarities in SMC beta-AR functional changes in hypertension and in ageing
      suggest that the underlying mechanisms are also analogous.

PMID- 10914633
TI  - Direct effects of varying doses of oestradiol on early embryonic development in
      in vitro culture of rat's two-cell embryos.
AB  - Hyperstimulation in the rat using pregnant mares' serum gonadotrophin (PMSG) has
      been known to cause death in pre-implantation embryos, as well as enhancement of
      oestradiol production. This study examines the effect of oestradiol, in levels
      that are found in hyperstimulated pregnant rats, on pre-implantation embryonic
      development. Using a simplified in vitro system, 2-cell embryos retrieved from
      rats on the 2nd day of pregnancy were cultured in rat two-cell embryo culture
      medium (R2ECM) containing pharmacological doses of oestradiol for 96 h and scored
      daily in the morning. Three ngxmL(-1) oestradiol reduced the incidence of >8-cell
      embryos to morulae on the 5th day and blastocysts on the 6th day of development.
      Most embryos were retarded at the lower cell stages on the 5th day and
      degenerated by the 6th day. None of the blastocysts expanded on the last day of
      culture. Fifteen ngxmL(-1) oestradiol accelerated embryo development on the 3rd
      day but retarded development on the 4th day, and increased the incidence of
      degenerated embryos by the 5th and 6th day of development. These results suggest
      that the elevated oestradiol may constitute a mechanism by which PMSG induces
      death in pre-implantation rat embryos, possibly via a direct action on the
      embryos.

PMID- 10914634
TI  - Reduction of the NO-mediated response in the rat aorta by metalloporphyrins.
AB  - Metalloporphyrins (MPs) have been found to affect the production of carbon
      monoxide (CO) and nitric oxide (NO). Unlike that for CO, little is known about
      the mechanism of action of MPs on the NO system. We determined the in vitro
      ability of ferrous protoporphyrin (heme, FePP), zinc protoporphyrin (ZnPP), and
      bilirubin (BR) to scavenge NO. Heme and ZnPP were studied in the rat aortic ring
      system for their ability to affect phenylephrine-induced contraction and
      methacholine-stimulated relaxation. Heme was found to be a good NO scavenger with
      a ks = 0.53 +/- 0.19 x 10(4) M(-1)xs(-1) (n = 6). ZnPP and BR did not scavenge
      NO. Neither heme nor ZnPP treatment affected the phenylephrine response as
      measured by -logEC50 and the maximal effect. However, heme and ZnPP treatments
      decreased the -logEC50 and the maximal effects of methacholine, therefore
      decreasing vasorelaxation. We conclude that when ZnPP is administered in vivo
      blood pressure should be carefully monitored.

PMID- 10914635
TI  - Tetracaine stimulates insulin secretion through the mobilization of Ca2+ from
      thapsigargin- and IP3-insensitive Ca2+ reservoir in pancreatic beta-cells.
AB  - The effect of tetracaine on 45Ca efflux, cytoplasmic Ca2+ concentration [Ca2+]i,
      and insulin secretion in isolated pancreatic islets and beta-cells was studied.
      In the absence of external Ca2+, tetracaine (0.1-2.0 mM) increased the 45Ca
      efflux from isolated islets in a dose-dependentOFF efflux caused by 50 mM K+ or
      by the association of carbachol (0.2 mM) and 50 mM K+. Tetracaine permanently
      increased the [Ca2+]i in isolated beta-cells in Ca2+-free medium enriched with
      2.8 mM glucose and 25 microM D-600 (methoxiverapamil). This effect was also
      observed in the presence of 10 mM caffeine or 1 microM thapsigargin. In the
      presence of 16.7 mM glucose, tetracaine transiently increased the insulin
      secretion from islets perfused in the absence and presence of external Ca2+.
      These data indicate that tetracaine mobilises Ca2+ from a thapsigargin
      insensitive store and stimulates insulin secretion in the absence of
      extracellular Ca2+. The increase in 45Ca efflux caused by high concentrations of
      K+ and by carbachol indicates that tetracaine did not interfere with a cation or
      inositol triphosphate sensitive Ca2+ pool in beta-cells.

PMID- 10914636
TI  - Effect of captopril on neurally induced contraction and relaxation of mesenteric
      arteries of renal hypertensive rats.
AB  - The effect of captopril treatment on neurally induced vasoconstrictor and
      vasodilator responses was examined in the isolated mesenteric arterial bed from
      normotensive and one-kidney, one clip hypertensive (1K1C) rats. In isolated
      mesenteric beds, electrical field stimulation (EFS) of perivascular nerves at
      basal tone induced a frequency-dependent increase in perfusion pressure that was
      greater in preparations from hypertensive rats compared with those from
      normotensive rats. Captopril treatment was associated with a decrease in
      vasoconstrictor responses in the hypertensive group compared with its non-treated
      control. Responses to norepinephrine (320 ng) were greater in hypertensive than
      normotensive groups; captopril reduced this response only in the hypertensive
      group. In preconstricted mesenteric arteries perfused with solutions containing
      guanethidine (5 microM) and atropine (1 microM), EFS elicited a frequency
      dependent decrease in perfusion pressure that was abolished by tetrodotoxin (1
      microM). Vasodilator responses to EFS were not affected by captopril treatment,
      although they were smaller in the hypertensive group. Acetylcholine (10 ng)
      induced similar decreases in perfusion pressure of normotensive and 1K1C groups;
      captopril did not influence these responses. These results indicate that
      captopril treatment does not affect the reduced neurogenic vasodilation but
      normalizes the augmented sympathetic-mediated vasoconstrictor responses of
      mesenteric resistance vessels of chronic 1K1C hypertensive rats.

PMID- 10914637
TI  - Role of glomerular nitric oxide in glycerol-induced acute renal failure.
AB  - Myoglobinuric acute renal failure remains one of the least understood clinical
      syndromes and the mediators involved remain obscure. The aim of the present study
      was to assess the role of nitric oxide in glycerol-induced acute renal failure
      under normal conditions and after uninephrectomy. Acute renal failure was induced
      in rats by injection of 50% glycerol (10 mL x kg(-1) body weight). Half of the
      animals were subjected to uninephrectomy two days before glycerol injection. Two
      days after the induction of acute renal failure, glomeruli from some animals were
      isolated and glomerular nitrite production was measured. Another group of animals
      was used for acute clearance studies. In this case, the effect of infusing either
      L-NAME or L-arginine was assayed. Glomerular nitrite production was significantly
      decreased in glycerol-induced acute renal failure. Glomeruli from
      uninephrectomized animals showed an increase in nitrite production, both in
      normal conditions and after glycerol injection, as compared with glomeruli from
      non-nephrectomized animals. L-NAME infusion worsened renal function in all the
      study groups, but more slowly in animals with glycerol-induced acute renal
      failure than in control rats. In uninephrectomized animals L-NAME reduced renal
      function more than in animals with two kidneys. In conclusion, in this model of
      acute renal failure the decrease in glomerular nitric oxide production plays an
      important role in the decrease in renal function. After uninephrectomy, an
      increase in glomerular nitric oxide synthesis plays a protective role against
      glycerol-induced acute renal failure.

PMID- 10914638
TI  - Molecular mechanism of doxorubicin-induced anticholinergic effect in guinea-pig
      atria.
AB  - The molecular mechanisms of anticholinergic actions of doxorubicin were examined
      by electrophysiological methods in atria and myocytes isolated from guinea-pig
      heart. A direct anticholinergic action of doxorubicin was confirmed with
      antagonistic action on carbachol-induced negative inotropic effect in atria. Both
      carbachol and adenosine produced shortening of action potential duration in atria
      measured by a microelectrode method. Doxorubicin (10-100 microM) inhibited the
      carbachol-induced action potential shortening in a concentration-dependent
      manner. However, doxorubicin did not antagonize the shortening elicited by
      adenosine. The whole-cell voltage clamp technique was performed to induce the
      muscarinic acetylcholine-receptor-operated K+ current (IK.ACh) in atrial myocytes
      loaded with GTP or GTPgammaS, a nonhydrolysable analogue of GTP. Doxorubicin (1
      100 microM) suppressed carbachol-induced IK.ACh in a concentration-dependent
      manner (IC50 = 5.6 microM). In contrast, doxorubicin (10 and 100 microM)
      suppressed neither adenosine-induced IK.ACh nor GTPgammaS-induced IK.ACh. These
      results indicate that doxorubicin produces a direct anticholinergic effect
      through the muscarinic receptors in atrial myocytes.

PMID- 10914639
TI  - Inhibition of cystic fibrosis transmembrane conductance regulator chloride
      channel currents by arachidonic acid.
AB  - Chloride permeation through the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl- channel is inhibited by a number of different classes of
      organic anions which are able to enter and block the channel pore from its
      cytoplasmic end. Here I show, using patch clamp recording from CFTR-transfected
      baby hamster kidney cell lines, that the cis-unsaturated fatty acid arachidonic
      acid also inhibits CFTR Cl- currents when applied to the cytoplasmic face of
      excised membrane patches. This inhibition was of a relatively high affinity
      compared with other known CFTR inhibitors, with an apparent Kd of 6.5 +/- 0.9
      microM. However, in contrast with known CFTR pore blockers, inhibition by
      arachidonic acid was only very weakly voltage dependent, and was insensitive to
      the extracellular Cl- concentration. Arachidonic acid-mediated inhibition of CFTR
      Cl- currents was not abrogated by inhibitors of lipoxygenases, cyclooxygenases or
      cytochrome P450, suggesting that arachidonic acid itself, rather than some
      metabolite, directly affects CFTR. Similar inhibition of CFTR Cl- currents was
      seen with other fatty acids, with the rank order of potency linoleic > or =
      arachidonic > or = oleic > elaidic > or = palmitic > or = myristic. These results
      identify fatty acids as novel high affinity modulators of the CFTR Cl- channel.

PMID- 10914640
TI  - Short-term exposure to homocysteine depresses rat aortic contractility by an
      endothelium-dependent mechanism.
AB  - The effect of short-term exposure to homocysteine (Hcy) on the contractile
      characteristics of rat aortic tissue was assessed both in vitro and in vivo. The
      contractile response of Hcy-treated aortic rings in culture for 1 or 4 days was
      unchanged from control responses. By comparison, aortic rings from animals
      injected with Hcy showed marked attenuation of response compared with controls
      injected with saline, cysteine or methionine. The contractile response to K+ was
      decreased within 24 hours of Hcy injection, whereas the response to both K+ (
      27%) and noradrenaline (-56%) was significantly decreased by 4 days. In contrast,
      the contractile response to phorbol-12,13-dibutyrate was not different between
      Hcy and control groups. Intimal rubbing completely restored the responsiveness of
      Hcy-treated tissue to K+ and noradrenaline. By comparison, L-NAME only partially
      restored contractile responsiveness, while the cyclooxygenase inhibitor
      indomethacin had no effect on contractile attenuation induced by Hcy. Western
      blot analysis showed a 2-fold increase of endothelial nitric oxide synthase
      (eNOS) and a 3-fold increase in inducible nitric oxide synthase (iNOS) protein
      expression in the aortic endothelial cells from Hcy-injected rats. The results
      indicate an early detectable effect of Hcy on the in vivo contractile properties
      of vascular smooth muscle. The effect is endothelium-mediated and may vary
      depending on the agonist studied. The mechanism is uncertain but appears to
      involve increased nitric oxide (NO) production. Finally, the data suggest that
      attenuation of contraction may not be due to a direct effect of Hcy but that the
      compound is modified or acts indirectly in vivo.

PMID- 10914641
TI  - Effects of Ca2+ concentration on GABA(B) receptor function in rat neocortical
      slices.
AB  - In rat neocortical slices maintained in Mg2+-free Kreb's medium, the effects of
      Ca2+ concentration on repetitive spontaneous discharges and on GABA(B) receptor
      mediated responses were investigated. Over a concentration range of 0.3-2.4 mM
      Ca2+, there was a reduction of discharge amplitude, with a 50 +/- 6.5% reduction
      in 0.3 mM Ca2+, whilst the burst frequency remained unaffected. Baclofen, the
      GABA(B) receptor agonist, produced a concentration-dependent depression of
      discharge frequency, reversibly antagonised by the antagonist (+)-(S)-5,5
      dimethylmorpholinyl-2-acetic acid (Sch 50911). The EC50 value for baclofen in 2.4
      mM Ca2+ was 11 microM, while the EC50 values in 0.3, 0.6, 1.2, and 1.8 mM Ca2+
      were 1.3, 2.5, 3.6, and 10 microM, respectively, resulting in 8.5, 4.4, 3.1, and
      1.1-fold leftward shifts. This enhanced action of baclofen in low extracellular
      Ca2+ concentrations in the neocortex may be the result of a lower concentration
      gradient which reinforces the action of baclofen.

PMID- 10914642
TI  - MRI analysis of brain atrophy after severe closed-head injury: relation to
      clinical status.
AB  - The purpose of this study was to determine the clinical correlates of
      supratentorial ventricular dilations and of corpus callosal atrophy at the
      subacute stage after a severe closed-head injury (CHI). Thirty-three CHI patients
      underwent MRI 2 months or more after injury. Morphometric measures were compared
      to clinical data (coma score, coma duration and Glasgow Outcome Scale). There
      were numerous significant correlations between clinical data and mid-third
      ventricle and frontal horns measurements. Fewer significant correlations were
      found with the lateral ventricle bodies and the corpus callosal body. There was
      no significant correlation with the posterior part of the corpus callosum and of
      the ventricles. Corpus callosum atrophy correlated significantly with anterior
      and deep ventricular dilatation. In conclusion, the best indicator of clinical
      status was ventriculomegaly, and particularly third ventricle enlargement, which
      probably reflects the extent of both anterior and deep white matter lesions.

PMID- 10914643
TI  - Reduced mortality after severe head injury will increase the demands for
      rehabilitation services.
AB  - PRIMARY OBJECTIVE: In 1989, a new therapy to reduce intracranial pressure in
      severely head-injured patients was introduced in Lund. The new treatment reduced
      mortality significantly. The present study describes the quality of life for the
      survivors. METHODS AND PROCEDURES: The study includes 53 patients treated during
      1989-1994, according to a new treatment protocol for increased intracranial
      pressure ('Lund concept' group). During 1982-1986, 38 patients were managed
      according to a protocol including high dose thiopentone ('Thiopentone' group).
      The two groups are compared regarding neurophysical and psychiatric symptoms as
      well as aspects regarding the patient's role, performance, interpersonal
      relationship, frictions, feelings and satisfaction in work, areas of social and
      leisure activities, and extended family. RESULTS: Mortality was reduced from 47%
      to 8%, but the number of patients with a persistent vegetative state and/or
      remaining severe disability did not increase. However, the number of patients
      with persisting emotional and intellectual deficits increased significantly.
      CONCLUSION: The new treatment regime has dramatically increased the number of
      survivors after severe head trauma. Although most patients have a favourable
      outcome, there are more patients with remaining sequelae and disabilities, and
      the demand for qualified rehabilitation has increased.

PMID- 10914644
TI  - Effect of depression on neuropsychological functioning in head injury: measurable
      but minimal.
AB  - The goals of the study were to determine how neuropsychological functioning is
      related to depressive status in persons with head injury, and to quantify this
      relationship from a clinically relevant standpoint. Participants were 175 adults
      involved in litigation, referred for evaluation of suspected head injury.
      Depression status was measured using the Depression Content (Dep) scale of the
      MMPI-2. Depression status was related to measures of visual attention and
      psychomotor skills, but not to other neuropsychological domains such as verbal
      ability, visual-spatial reasoning, or encoding/organization. However, differences
      between low Dep and high Dep groups were minimal from a clinical standpoint.
      Depression appeared to contribute to an increased risk of impaired
      neuropsychological performance across domains, but only in persons not severely
      compromised by neuropsychological deficits. Overall, the results indicated a
      small effect of depression on neuropsychological functioning that is likely only
      detectable in persons whose neuropsychological compromise is relatively minimal.

PMID- 10914645
TI  - Executive function and verbal working memory in adolescents with closed head
      injury (CHI).
AB  - The relationship between executive function (EF) and working memory (WM) was
      studied in eight adolescents with closed head injury (CHI) and eight controls,
      matched for age, gender and socioeconomic status (SES). A cognitive-linguistic
      test (Scales of Cognitive Ability for Traumatic Brain Injury, SCATBI) was used to
      group CHI participants by seventy. EF was tested with a measure of daily
      functioning (Pro-Ex) and WM was tested with a recognition memory task (RMT). When
      all subject test data were grouped, a positive linear correlation was found for
      the Pro-Ex and the RMT. A strong-to-moderate positive correlation was found for
      components of the EF measure and the RMT. Severity of injury influenced test
      performance for both the EF and WM measures, with a significance between group
      effects found on the RMT task. Results indicate a relationship between executive
      function and working memory, severity of injury and test performance and the need
      to assess EF of CHI adolescents with a measure of daily functioning.

PMID- 10914646
TI  - Neurobehavioural outcomes of penetrating and tangential gunshot wounds to the
      head.
AB  - OBJECTIVE: The objective of this study was to compare penetrating and tangential
      gunshot wounds to the head with regards to demographic, neurobehavioural and
      clinical outcome measures. METHODS: Twenty-nine patients with penetrating gunshot
      wounds (P-GSW) and 11 patients with tangential gunshot wound (T-GSW) to the head
      admitted to an acute neurotrauma service were compared using standardized
      neurobehavioural and clinical outcome measures. RESULTS: The mean GCS was 10.5 +/
      0.79 for the P-GSW group and 13.4 +/- 0.72 for the T-GSW group. The mean AIS-CNS
      for the P-GSW group was 5.00 +/- 0 and for the T-GSW group was 3.7 +/- 0.27.
      Significance was found on Digit Span (p < 0.05) and Block Design (p < 0.009)
      subtests. Outcomes between the two groups were similar, except for significant
      differences were found for acute length of stay (LOS) (P-GSW was 47.72 +/- 13.2
      and T-GSW group was 13.0 +/- 1.3, p = 0.005) and for acute care charges (P-GSW
      group was $150,533 +/- 23,834 and T-GSW group was $70,712 +/- 16,587, p = 0.05).
      CONCLUSIONS: Initially, a penetrating gunshot wound is a more severe and costly
      injury than a tangential gunshot wound to the head, however T-GSW possess
      significant deficits and, if the patient survives past the acute phase of
      recovery, the two groups have similar functional outcomes. Future standard
      classification, neuropsychological, and clinical outcome measures.

PMID- 10914647
TI  - Factors associated with insomnia among post-acute traumatic brain injury
      survivors.
AB  - This study investigated the relationships between insomnia and select
      demographic, injury and psychosocial variables in post-acute, traumatic brain
      injury. Clinical assessment of sleep and mood was undertaken via objective
      measures and a diagnostic interview among 91 consecutive brain injury admissions
      to an outpatient neurorehabilitation clinic. No associations between insomnia and
      gender, education, age, and time since injury were found. A logistic regression
      model of insomnia prediction based upon the Beck Depression Inventory (BDI), self
      reported pain disturbance, litigation and Glasgow Coma Score (GCS) correctly
      classified 87% of the sample with respect to the presence or absence of insomnia;
      however, depression and injury severity were the only variables that made a
      significant unique contribution to the prediction of insomnia. It is concluded
      that among post-acute traumatic brain injury patients, insomnia is linked with
      both the presence of depression and a history of milder brain injuries. This
      suggests that the determinants of insomnia may differ from the acute to the post
      acute phase, with neurological factors playing a primary role early in the
      recovery process and psychosocial factors ascending later. Therefore, assessment
      and treatment of insomnia must give careful attention to the larger psychosocial
      context in which the sleep disorder emerges, particularly to role of emotional
      disturbance.

PMID- 10914648
TI  - Effect of growth hormone on brain oedema caused by a cryogenic brain injury model
      in rats.
AB  - Although growth hormone (GH) is a potential agent to counteract the catabolic
      response to general and head injuries, the complications of GH treatment have
      been little studied. To evaluate the safety of GH in head trauma patients, it was
      investigated whether GH affects brain oedema caused by brain injury, using a rat
      freeze-injury model. Male Wistar rats (n = 28) were divided into four groups
      according to the substance injected (GH vs. saline) and whether brain was injured
      or not. GH (0.8 IU/kg) or saline was injected subcutaneously every 24 hours. In
      the injury groups, immediately before the first injection of GH, an aluminum rod
      cooled to -50 degrees C was placed on the right parietal region for 4 minutes,
      under anaesthesia. At 96 hours after the insult, brain and skeletal muscle were
      excised and their water content was measured, by drying. Freeze injury of the
      brain caused an increase in water content in skeletal muscle. GH injection
      augmented this oedema in skeletal muscle. Freeze injury of the brain also caused
      an increase in water content in the injured and non-injured hemispheres of brain
      and cerebellum. GH administration did not exacerbate brain oedema caused by brain
      injury in this model.

PMID- 10914649
TI  - Molecular beacon polymerase chain reaction detection of Escherichia coli O157:H7
      in milk.
AB  - A fluorescently labeled oligonucleotide probe (molecular beacon) was applied to
      detect Escherichia coli O157:H7 in artificially contaminated skim milk during
      polymerase chain reaction (PCR) amplification of extracted DNA. The probe was
      designed to hybridize with a region of the slt-II gene coding for the A subunit
      and to fluoresce when the hairpin-stem conformation was linearized upon
      hybridization to the target sequence. The molecular beacon was incorporated into
      PCR reactions containing DNA extracted from artificially contaminated skim milk.
      The degree of fluorescence was monitored in PCR reactions containing 10(3),
      10(5), and 10(7) CFU of E. coli O157:H7 per ml and was found to correlate with
      the amount of template in each reaction. Fluorescence significantly increased
      above background levels by cycle 8, 14, or 14 in reactions containing DNA from
      the 10(7)-, 10(5)-, or 10(3)-CFU/ml template, respectively (P < 0.05). Molecular
      beacon PCR demonstrated positive results more rapidly than traditional agarose
      gel electrophoresis analysis of PCR products. Use of molecular beacons allows
      real-time monitoring of PCR reactions, and the closed-tube format allows
      simultaneous detection and confirmation of target amplicons without the need for
      agarose gel electrophoresis and/or Southern blotting. This is the first report of
      a stem-and-loop molecular beacon being applied for direct detection of a pathogen
      in food.

PMID- 10914650
TI  - Evaluation of the Reveal and SafePath rapid Escherichia coli O157 detection tests
      for use on bovine feces and carcasses.
AB  - The Reveal (Neogen Corp., Lansing, Mich.) and SafePath (SafePath Laboratories
      LLC, St. Paul, Minn.) tests were evaluated for their performance as beef fecal
      and beef carcass Escherichia coli O157:H7 monitoring tests. Agreement between
      these tests and a reference test system was determined using naturally
      contaminated bovine feces and beef carcasses. The reference system utilized
      immunomagnetic separation with plating onto cefixime, tellurite, sorbitol
      MacConkey agar, followed by colony testing using a serum agglutination test for
      the O157 antigen. Relative to this reference method, the Reveal test showed a
      sensitivity of 46% and a specificity of 82% on bovine feces and a specificity of
      99% on carcass samples. The SafePath test, demonstrated a significantly higher
      sensitivity at 79% and a similar specificity of 79%. On carcass samples the
      SafePath test performed similarly to the Reveal test, demonstrating a specificity
      of 100% relative to the reference system. There was an insufficient number of E.
      coli O157-positive carcass samples to estimate precisely the sensitivity of these
      two methods. Both methods show promise as rapid carcass monitoring tests, but
      further field testing to estimate sensitivity is needed to complete their
      evaluation. The proportion of positive fecal samples for E. coli O157:H7 by the
      reference method ranged from 10.2% to 36% in 10 lots of cattle with an overall
      mean of 17.3% (39/225). Quarter carcass sponging of 125 carcasses revealed 1.6%
      positive for the pathogen (2/125).

PMID- 10914651
TI  - Commercial field trial evaluation of mucosal starter culture to reduce Salmonella
      incidence in processed broiler carcasses.
AB  - A series of four paired-house studies was conducted in Arkansas, Alabama, and
      Georgia (two farms) to determine the efficacy of Mucosal Starter Culture (MSC) in
      eliminating or reducing salmonellae in broiler chickens. Randomly designated
      chicks were treated twice with MSC. First they were sprayed with an MSC solution
      using a spray vaccination cabinet in the hatchery, and then they received MSC in
      the first drinking water at the growing house. Chicks were grown in identically
      constructed and equipped paired houses managed by the same grower. At the end of
      grow-out, broilers were tested for the presence of salmonellae on the farm and
      during processing. In three trials where no hatchery salmonellae were found, less
      salmonellae were found on MSC-treated chickens compared to untreated chickens. On
      the farm at the end of grow-out, salmonellae were detected in 54 of 150 untreated
      control chickens compared to 40 of 180 MSC-treated chickens. In the processing
      plant, significantly (P < or = 0.05) more salmonellae were detected on prechill
      untreated control carcasses (23 of 180) compared to MSC-treated carcasses (12 of
      180) and on untreated postchill processed carcasses (9 of 180) compared to MSC
      treated carcasses (0 of 180). In one trial where appreciable (28% of egg shell
      samples) salmonellae was found before treatment with the MSC, more salmonellae
      were found in the treated birds than in the control birds both on the farm and
      after processing. These data confirm that when salmonellae levels were controlled
      in the hatchery, a significant reduction in the salmonellae was found on
      processed broiler carcasses treated with MSC and that this reduction in
      salmonellae was carried through processing to the final processed carcass, thus
      potentially reducing consumer exposure to salmonellae.

PMID- 10914652
TI  - Reduction of Salmonella spp. and strains of Escherichia coli O157:H7 by gamma
      radiation of inoculated sprouts.
AB  - There have been several recent outbreaks of salmonellosis and infections with
      Escherichia coli O157:H7 linked to the consumption of raw sprouts. Use of
      ionizing radiation was investigated as a means to reduce or to totally inactivate
      these pathogens, if present, on the sprouts. The radiation D value, which is the
      amount of irradiation in kilograys for a 1-log reduction in cell numbers, for
      these pathogens was established using a minimum of five doses at 19 +/- 1 degrees
      C. Before inoculation, the sprouts were irradiated to 6 kGy to remove the
      background microflora. The sprouts were inoculated either with Salmonella spp.
      cocktails made with either meat or vegetable isolates or with E. coli O157:H7
      cocktails made with either meat or vegetable isolates. The radiation D values for
      the Salmonella spp. cocktails on sprouts were 0.54 and 0.46 kGy, respectively,
      for the meat and vegetable isolates. The radiation D values for the E. coli
      O157:H7 cocktails on sprouts were 0.34 and 0.30 kGy, respectively, for the meat
      and vegetable isolates. Salmonella was not detected by enrichment culture on
      sprouts grown from alfalfa seeds naturally contaminated with Salmonella after the
      sprouts were irradiated to a dose of 0.5 kGy or greater. Ionizing radiation is a
      process that can be used to reduce the population of pathogens on sprouts.

PMID- 10914653
TI  - Attachment and growth of Salmonella Chester on apple fruits and in vivo response
      of attached bacteria to sanitizer treatments.
AB  - Attachment and growth of Salmonella Chester on fresh-cut apple disks and in vivo
      response of attached bacteria to sanitizer treatments were investigated. Apple
      disks (14 mm in diameter and 3 to 4 mm in thickness) were immersed in a bacterial
      suspension that contained 8.17 log CFU/ml of Salmonella Chester and air dried at
      room temperature for 10 min. After two rinses, the population of Salmonella
      Chester retained on apple disks that contained no skin was 13 to 19% higher than
      that retained on disks that contained skin, indicating that Salmonella Chester
      attached more firmly to the surfaces of injured tissue than to the unbroken skin.
      The number of bacteria attached to the disk was not affected by the immersion
      time but was directly proportional to the concentration of bacteria in the
      suspension. The distribution of artificially inoculated Salmonella Chester on the
      surfaces of three different parts of whole fruit was determined; 94% of attached
      bacteria was found on the stem and calyx cavity areas and 6% on the skin of the
      remaining area of the fruit. Despite their acidic pH (4.1), apple disks supported
      the growth of Salmonella Chester at 20 degrees C but not at 8 degrees C. All four
      sanitizers tested in the study, including 6% hydrogen peroxide, 2% trisodium
      phosphate, 0.36% calcium hypochlorite, and 1.76% sodium hypochlorite, were
      effective in reducing the population of Salmonella Chester on apple disks by 1 to
      2 logs. However, 5 to 13% of bacteria survived the sanitizer treatments. Hydrogen
      peroxide, which reduced the population of Salmonella Chester on skin by 3 to 4
      logs and the population of bacteria on stem or calyx by 1 to 2 logs, was the most
      effective among the four sanitizers tested. Firm attachment of bacteria on calyx,
      stem, and injured tissue and partial resistance of attached bacteria to sanitizer
      treatments are two major obstacles to be considered when developing methods for
      cleaning and decontaminating apple fruits destined for juice production and fresh
      consumption.

PMID- 10914654
TI  - Combined effects of hydrostatic pressure, temperature, and the addition of allyl
      isothiocyanate on inactivation of Escherichia coli.
AB  - Combined effects of hydrostatic pressure, temperature, and the addition of allyl
      isothiocyanate (AIT) on the inactivation of Escherichia coli, including type
      O157, were investigated. Inactivation to undetectable levels by hydrostatic
      pressure alone requires 400 to 600 MPa. E. coli growth was delayed with
      increasing of applied pressure and the AIT concentration added subsequently. The
      antibacterial effects of AIT vapor increased on JCM 1649 and IFO 3301 after
      pressurization. The bactericidal effects of pressurization with the addition of
      AIT at 4 degrees C or 40 degrees C were greater than at 20 degrees C, and all
      bacteria tested were effectively killed at 200 or 250 MPa with 10 to 80 microg/ml
      of AIT. We tried to apply the combined treatment to a food product "Asazuke" (low
      salt vegetables), and it was confirmed that E. coli inoculated into the product
      was inactivated the same as in the in vitro test. We also studied the
      inactivation mechanism behind pressurization with AIT from the relationship
      between pressure resistance and precultivation temperature, and it was suggested
      that destruction of membrane structure caused bacterial kill.

PMID- 10914656
TI  - Effectiveness of two cooking systems in destroying Escherichia coli O157:H7 and
      Listeria monocytogenes in ground beef patties.
AB  - A rapid, high-temperature double-sided grilling-broiling (DGB) system was
      compared to a single-sided broiling (SSB) system for cooking of foodservice
      ground beef patties to reduce microbial numbers and maintain textural quality.
      Patties (110 g) containing either Escherichia coli O157:H7 or Listeria
      monocytogenes (10(6-7) CFU/g) were cooked to target internal temperatures of 60
      or 68 degrees C on each cooking system and immediately removed from the grills
      without the additional holding time at 60 or 68 degrees C that is recommended for
      foodservice cooking of ground beef patties. Actual final internal temperature
      attained, position on the grill, degree of doneness, cooking time, after-cook
      weight, texture characteristics, and bacterial counts of the patties were
      monitored. The DGB reduced E. coli O157:H7 and L. monocytogenes populations in
      ground beef patties by 5.7 log10 and 5.4 log10 CFU/g, respectively, when cooked
      to a target temperature of 60 degrees C (actual final internal temperature of
      71.2 degrees C) and by 6.1 log10 and 5.6 log10 CFU/g, respectively, when cooked
      to a target temperature of 68 degrees C (actual final internal temperature of
      75.8 degree C). The SSB reduced E. coli O157:H7 and L. monocytogenes populations
      by 1.3 log10 and 1.8 log10 CFU/g, respectively, when cooked to a target
      temperature of 60 degrees C (actual final internal temperature of 62.7 degrees C)
      and by 2.9 log10 and 3.6 log10 CFU/g, respectively, when cooked to a target
      temperature of 68 degrees C (actual final internal temperature of 69.3 degrees
      C). The DGB system effected a higher, more rapid temperature increase in patties
      cooked to either target temperature compared to the SSB system. This higher
      temperature was more effective in destroying pathogens in beef patties. Texture
      analyses determined that patties cooked on the DGB system had significantly
      higher values for springiness, adhesiveness, and product height as compared to
      the SSB system, and patties cooked on either system had significantly higher
      hardness, gumminess, chewiness, and product height values at the target
      temperature of 68 degrees C as compared to 60 degrees C.

PMID- 10914655
TI  - Antimicrobial activity of a 14-residue synthetic peptide against foodborne
      microorganisms.
AB  - A chemically synthesized short-chain peptide composed of six leucine and eight
      lysine (6K8L) residues was demonstrated to be biocidal against several foodborne
      organisms including Escherichia coli O157:H7, Listeria monocytogenes, Pseudomonas
      fluorescens, and Kluyveromyces marxianus suspended in phosphate buffer at
      concentrations of 5 to 50 microg/ml. All strains were reduced by 3 log10 CFU/ml
      within 10 min at peptide concentrations of <10 microg/ml. The peptide reduced by
      3 log10 CFU/ml E. coli O157:H7 counts in apple juice and was active over the pH
      range of 3.5 to 7. Peptide concentrations of 100 microg/ml inhibited the aerobic
      and anaerobic microorganisms present in meat exudate liquid. However, the peptide
      was not effective against E. coli O157:H7 in skim milk at concentrations up to
      100 microg/ml.

PMID- 10914657
TI  - Characterization of Vibrio parahaemolyticus isolates obtained from foodborne
      illness outbreaks during 1992 through 1995 in Taiwan.
AB  - Vibrio parahaemolyticus is an important foodborne pathogen in Taiwan and many
      other Asian countries. A total of 371 isolates of V. parahaemolyticus collected
      from patients involved in foodborne illness outbreaks in Taiwan from 1992 to 1995
      were characterized. These isolates had typical biochemical characteristics and
      only 4% were urease positive. The most frequently isolated serovars were O5:K15
      (18.5%), O4:K8 (16.2%), O3:K29 (12.5%), O1:K56 (8.3%), O2:K3 (6.5%), and O4:K12
      (6.0%). Most of the isolates were susceptible to nalidixic acid, tetracycline,
      tobramycin, cephalothin, and gentamicin. About 10% of the isolates were resistant
      to seven or more antibiotics. Approximately 92.4% of these V. parahaemolyticus
      showed beta-hemolysis on Wagatsuma blood agar plate and approximately 62.1% of
      these isolates exhibited detectable amounts of thermostable direct hemolysin.
      Most of the isolates examined exhibited two copies of tdh genes on the 1.3- and
      2.5-kb HindIII-digested chromosome fragments with several variations on other
      fragments. A pulsed-field gel electrophoresis (PFGE) subspecies typing scheme was
      used to analyze these domestic isolates and the O3:K6 strains from Japan, Korea,
      and Taiwan. Fifty seven patterns were differentiated with A, B, C, E, and H being
      the major domestic types (cumulatively 76% of isolates), while O3:K6 strains
      (PFGE type I), abruptly occurring since 1996, were genetically distant from the
      major domestic types.

PMID- 10914658
TI  - Growth and survival of Escherichia coli O157:H7 and Listeria monocytogenes in egg
      products held at different temperatures.
AB  - Growth and survival of Escherichia coli O157:H7 and Listeria monocytogenes in
      steamed eggs and scrambled eggs held at different temperatures (5, 18, 22, 37,
      55, and 60 degrees C) were investigated in the present study. Among the holding
      temperatures tested, both pathogens multiplied best at 37 degrees C followed by
      22, 18, and 5 degrees C. In general, E. coli O157:H7 grew better in the egg
      products than L. monocytogenes did at all the storage temperatures tested except
      at 5 degrees C. E. coli O157:H7 did not grow in steamed eggs and scrambled eggs
      held at 5 degrees C. L. monocytogenes showed a slight population increase of
      approximately 0.6 to 0.9 log CFU/g in these egg products at the end of the 36-h
      storage period at 5 degrees C. The population of both pathogens detected in the
      egg products was affected by the initial population, holding temperature, and
      length of the holding period. It was also noted that L. monocytogenes was more
      susceptible than E. coli O157:H7 in steamed eggs held at 60 degrees C. After
      holding at 60 degrees C for 1 h, no detectable viable cells of L. monocytogenes
      with a population reduction of 5.4 log CFU/g was observed in steamed eggs,
      whereas a lower population reduction of only approximately 0.5 log CFU/ml was
      noted for E. coli O157:H7.

PMID- 10914659
TI  - Vancomycin resistance and antibiotic susceptibility of enterococci in raw meat.
AB  - The purpose of this study was to investigate antimicrobial resistance, in
      particular to vancomycin, of enterococci in samples (100) of meat (beef, chicken,
      turkey, lamb, and pork) sold in retail outlets of Catanzaro (Italy). Enterococci
      were identified to the species level. Antimicrobial susceptibility tests for a
      large spectrum of antibiotics including glycopeptides were performed by the disk
      diffusion method. Kappa statistic was used to evaluate associations of resistance
      to vancomycin with other antimicrobials. Enterococci were isolated from 45% of
      the samples, mostly from chicken meat (65.4%). Overall, 29% of samples were
      contaminated by vancomycin-resistant enterococci (VRE), whereas among those
      positive they represented 64.4% of isolates. Higher prevalence of vancomycin
      resistance was found in chicken samples (76.5%). The overall resistance to
      teicoplanin (TRE) was 30%, whereas among those positive, TRE represented 66.7% of
      isolates. The most frequent isolates were Enterococcus faecium (35.6%) and
      Enterococcus faecalis (33.3%). Resistance to vancomycin and teicoplanin was
      observed in 75% and 78.5% of E. faecium, and in 40% and 46.7% of E. faecalis,
      respectively. Most strains were susceptible to ampicillin (80%), while 88.9% were
      resistant to methicillin. The most effective antimicrobials were imipenem (73.3%
      susceptible) and rifampin (80%). The highest prevalence of resistance was for
      streptomycin (88.9%), tetracycline (84.4%), and erythromycin (75.6%). Resistance
      to vancomycin was significantly associated to methicillin, teicoplanin,
      erythromycin, tetracycline, and chloramphenicol. Further investigations about
      enterococcal colonization and infections in community and hospital subjects are
      needed.

PMID- 10914660
TI  - Behavior of Listeria monocytogenes in pasteurized milk during fermentation with
      lactic acid bacteria.
AB  - The behavior of Listeria monocytogenes in pasteurized milk during fermentation
      with starter and nonstarter lactic acid bacteria was investigated. Pasteurized
      milk was co-inoculated with approximately 10(4) CFU/ml of L. monocytogenes and
      10(6) CFU/ml of Lactococcus lactis, Lactococcus cremoris, Lactobacillus
      plantarum, Lactobacillus bulgaricus, or Streptococcus thermophilus. Inoculated
      milks were incubated at 30 degrees C or 37 degrees C for 24 to 72 h. Listeria
      monocytogenes survived and also grew to some extent during incubation in the
      presence of all starter cultures; however, inhibition ranged from 83 to 100%
      based on maximum cell populations. During incubation with L. bulgaricus and L.
      plantarum, L. monocytogenes was completely inactivated after 20 h and 64 h of
      incubation at 37 degrees C and 30 degrees C, respectively. The pH of the
      fermenting milks declined steadily throughout the fermentation periods and was
      approximately 4.2 at the conclusion of the experimental period regardless both of
      the starter culture and pathogen combination or the temperature of incubation.

PMID- 10914661
TI  - Use of capillary tubes and plate heat exchanger to validate U.S. Department of
      Agriculture pasteurization protocols for elimination of Listeria monocytogenes in
      liquid egg products.
AB  - D-values for a five-strain cocktail of Listeria monocytogenes in five different
      liquid egg products (whole egg, egg yolk, egg white, egg yolk + 5% sucrose + 5%
      NaCl, and egg yolk + 10% NaCl) were determined using 100-microl capillary tubes.
      The egg products were inoculated with approximately 1 x 10(10) organisms/ml and
      heated in capillary tubes to temperatures ranging from 53 to 69 degrees C for
      various time intervals. Using a pilot scale plate heat exchanger, the U.S.
      Department of Agriculture (USDA) protocols for pasteurization were also evaluated
      using egg products inoculated with approximately 1 x 10(7) L. monocytogenes/ml.
      Results of experiments with capillary tubes suggested that all processes would
      result in less than the 9D process recommended by USDA. Moreover, although
      pasteurization with a plate heat exchanger provided greater lethality than did
      capillary tubes, all products still received less than a 5.4D process. Hence,
      these results suggest that the current USDA protocol may not be adequate to
      assure a large margin of safety.

PMID- 10914662
TI  - Growth of Bacillus cereus on solid media as affected by agar, sodium chloride,
      and potassium sorbate.
AB  - The effect of two independent variables: microstructure, as modified by the agar
      content (1.0, 4.0, 7.0%), and water activity (a(w)), as modified by the NaCl
      content (0.5, 2.5, 4.5%), in the absence or in the presence of potassium sorbate
      (0.0; 2,000 ppm) on Bacillus cereus growth on solid media was studied. The time
      to visible growth (TVG) and the radial growth rate (RGR) of colonies were
      evaluated. TVG was not affected by microstructure and K-sorbate, although when
      a(w) was reduced, TVG tended to increase. RGR depended on linear effects of
      microstructure and a(w) variables and their interaction. When K-sorbate was added
      to cultural media, RGR was reduced significantly. However, in the presence of K
      sorbate, RGR was found to change only when a(w) vas varied.

PMID- 10914663
TI  - Isolation and identification of nontuberculous mycobacteria from foods as
      possible exposure sources.
AB  - A variety of foods collected from local supermarkets and produce stands were
      examined as possible sources of nontuberculous mycobacterial exposure. Food
      samples were combined with sterile ultrapure water and manually shaken. To remove
      large particles, the suspensions were filtered through a sterile strainer,
      centrifuged, and the supernatants were discarded. The food pellets were stored at
      -75 degrees C. The pellets were treated with either oxalic acid or sodium
      hydroxide-sodium citrate solutions to reduce contamination by nonmycobacterial
      organisms. Decontaminated pellets were cultured on both Middlebrook 7H10C agar
      and Middlebrook 7H10C agar with supplemental malachite green. Plates were
      observed for growth at 2 and 8 weeks. Isolates demonstrating acid-fastness were
      identified to species using polymerase chain reaction and restriction enzyme
      analysis. Nontuberculous mycobacteria (NTM) were recovered from 25 of 121 foods.
      Six different species of NTM were isolated, the most predominant being
      Mycobacterium avium.

PMID- 10914664
TI  - Effects of gamma radiation on sensory qualities, microbiological and chemical
      properties of salted and fermented squid.
AB  - The effects of gamma radiation on sensory quality, microbial population, and
      chemical properties of salted and fermented squid were investigated. Squid
      (Todarodes pacificus) was sliced, washed, and then salted with 5, 10, and 20%
      (wt/wt) sodium chloride. Salted squid was irradiated with dosages of 0, 2.5, 5.0,
      and 10 kGy of gamma radiation and fermented at 15 degrees C for 50 days.
      Proximate composition, salinity, water activity, sensory evaluation, and total
      microbiological populations were examined. Chemical analyses providing
      information on degree of fermentation, such as amino nitrogen (AN), volatile
      basic nitrogen (VBN), trimethylamine (TMA), and hypoxanthine (Hx) were also
      conducted. Irradiated squid was not different in proximate composition, salinity,
      and water activity from nonirradiated squid. Sensory evaluation scores, total
      bacteria populations, and pH values were variable depending on salt concentration
      and irradiation dose. During fermentation, AN, VBN, TMA, and Hx contents
      increased rapidly as the salt concentration and irradiation dose decreased.
      Specifically, these chemical compounds of salted and fermented squid prepared
      with 10% salt and 10 kGy of gamma radiation maintained the appropriate level of
      fermentation. The present results showed that the combination of low salt
      concentration (10%) and gamma radiation was effective in processing salted and
      fermented squid and extending its shelf life compared to control (20% of salt)
      without adding any food additives.

PMID- 10914665
TI  - Effects of gamma radiation on the conformational and antigenic properties of a
      heat-stable major allergen in brown shrimp.
AB  - This study was performed to evaluate the application of food irradiation
      technology as a method for reducing shrimp allergy without adverse effects.
      Shrimp heat-stable protein (HSP) was isolated and gamma irradiated at 0, 1, 3, 5,
      7, or 10 kGy in the condition of solution (1 mg/ml), and fresh shrimp was also
      irradiated. Conformational change of irradiated HSP was monitored by means of
      spectrometric measures, enzyme-linked immunosorbent assay with mouse monoclonal
      antibody, or human patients' sera and sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis. The ability of the immunoglobulin E of patients allergic to
      shrimp to bind to irradiated HSP was dose dependently reduced. The amount of
      intact HSP in an irradiated solution was reduced by gamma irradiation, depending
      on the dose. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed
      that the main band disappeared and the traces induced from coagulation appeared
      at a higher molecular weight zone. The binding ability of immunoglobulin E to
      allergens in the extracts from irradiated shrimp decreased, depending on the
      dose. The results provide a new method so that food irradiation technology can be
      applied to reduce allergenicity of shrimp.

PMID- 10914666
TI  - Genotoxicity testing of cooked cured meat pigment (CCMP) and meat emulsion
      coagulates prepared with CCMP.
AB  - The preformed cooked cured meat pigment (CCMP) synthesized directly from bovine
      red blood cells or through a hemin intermediate was found to be a viable colorant
      for application to comminuted pork as a nitrite substitute. However the
      genotoxicity of CCMP and meat emulsion coagulates prepared with CCMP has not been
      evaluated. Therefore the objectives of this work were to investigate genotoxicity
      of CCMP and the influence of CCMP addition on genotoxicity and the content of
      residual nitrite in model meat emulsion coagulates. Meat emulsions were prepared
      from white (musculus longissimus dorsi) and red (musculus quadriceps femoris)
      pork muscles with two different amounts of synthesized pigment CCMP.
      Comparatively, emulsions with fixed addition of nitrite salt and emulsions
      without any addition for color development were made. Genotoxicity of CCMP and
      meat emulsion coagulates was tested with the SOS/umu test and the Ames test.
      Neither CCMP nor meat emulsion coagulates prepared with CCMP or nitrite salt were
      genotoxic in the SOS/umu test. In the Ames test using Salmonella Typhimurium
      strains TA98 and TA100 samples of coagulates prepared with CCMP and with nitrite
      showed weak mutagenic activity in Salmonella Typhimurium strain TA100 but only in
      the absence of the metabolic activation, while CCMP was not mutagenic. Coagulates
      prepared with CCMP contained significantly less residual nitrite than coagulates
      prepared with nitrite salt. These results indicate that from the human health
      standpoint the substitution of nitrite salt with CCMP would be highly
      recommendable.

PMID- 10914667
TI  - Qualitative detection of tetracycline residues in milk with a luminescence-based
      microbial method: the effect of milk composition and assay performance in
      relation to an immunoassay and a microbial inhibition assay.
AB  - Performance of Tet-Lux, a newly developed microbiological test for the detection
      of tetracycline residues in raw milk, based on tetracycline-controlled
      luminescence activation of the test bacteria, was evaluated in bovine milks with
      variable amounts of somatic cells, bacteria, fat, protein, and natural inhibitory
      compounds. The sensitivity of Tet-Lux was also compared to a commercially
      available tetracycline immunoassay (Snap, Idexx Laboratories Inc.) and to a
      microbial inhibition test (Delvotest SP, Gist-Brogades). There were slight
      differences in the luminescence signals between different milk samples, but no
      single factor could be pointed out to be responsible for them. There appeared to
      be a modest inverse relationship between luminescence and increasing fat and
      protein content. The amount of somatic cells, bacteria, and the natural
      inhibitors lysozyme and lactoferrin did not affect the luminescence response. The
      test fulfilled the sensitivity requirement specified by the European Union
      (maximum residue limit 100 ng/ml for tetracyclines). The Tet-Lux test was clearly
      more sensitive to all tetracyclines tested (oxytetracycline, tetracycline,
      chlortetracycline, doxycycline, demeclocycline, methacycline, minocycline) than
      Delvotest SP, and for five tetracyclines out of seven more sensitive than Snap.
      The test provides a fast, simple, and robust microbial method for the qualitative
      detection of tetracycline residues in milk.

PMID- 10914668
TI  - Isolation of Salmonella spp. from the housefly, Musca domestica L., and the dump
      fly, Hydrotaea aenescens (Wiedemann) (Diptera: Muscidae), at caged-layer houses.
AB  - Flies, especially houseflies, are widely recognized as potential reservoirs and
      vectors of foodborne Salmonella pathogens. In this study, flies were collected at
      caged-layer facilities that had produced eggs that were implicated as the food
      vehicle in two recent outbreaks of Salmonella Enteritidis infections. The flies
      were separated by species into pools for microbiological testing. A total of 15
      species pools of houseflies, Musca domestica L., and 7 species pools of bronze
      dump flies, Hydrotaea aenescens (Wiedemann) (Diptera: Muscidae), were analyzed.
      Salmonella Enteritidis was isolated from 2 of the 15 pools of houseflies. Other
      species of Salmonella were isolated from three pools of flies, including
      Salmonella Infantis from houseflies and from dump flies and Salmonella Heidelberg
      from houseflies. Salmonella Mbandaka was isolated from a lesser mealworm,
      Alphitobius diaperinus (Panzer) (Coleoptera: Tenebrionidae).

PMID- 10914669
TI  - Efficacy of alkaline washing for the decontamination of orange fruit surfaces
      inoculated with Escherichia coli.
AB  - The effectiveness of washing treatments to decontaminate orange fruit surfaces
      inoculated with Escherichia coli was evaluated. Washing on roller brushes with
      fruit cleaners or sanitizers followed by potable water rinse reduced E. coli by
      1.9 to 3.5 log cycles. Prewetting fruit for 30 s before washing provided no
      significant benefit in most cases. Additional sanitizing treatments either with
      chlorine or acid sanitizers did not enhance the results of alkaline washing. In
      general, high pH washing solutions (pH 11.8) applied with an adequate spray
      volume effectively reduced the surface contamination of fruit that lowered the
      microbial load of fresh juice as well.

PMID- 10914670
TI  - A survey of water activity and pH values in fresh pasta packed under modified
      atmosphere manufactured in Argentina and Uruguay.
AB  - The water activity (a(w)) and pH values of commercially available filled fresh
      pasta and gnocchi packed under modified atmosphere and manufactured in Argentina
      and Uruguay were examined. The retail survey included 58 samples (several brands)
      of filled pasta and 11 samples of gnocchi. Fillings consisted of different
      combinations of cheese (various types), beef, ricotta, ham, chicken, and spinach.
      The survey revealed that the a(w) values of the 58 samples of filled pasta ranged
      from 0.916 to 0.973, and their pH values ranged from 5.2 to 7.0. The a(w) of
      gnocchi was consistently higher and ranged from 0.936 to 0.983, with pH values
      from 4.8 to 6.4. Some samples of filled pasta and most gnocchi samples were found
      to have a(w) and pH values that would support growth of spores of Clostridium
      botulinum, if present, under conditions of temperature abuse (i.e., 30 degrees
      C).

PMID- 10914671
TI  - Buffalo-milk enzyme levels, their sensitivity to heat inactivation, and their
      possible use as markers for pasteurization.
AB  - The activities and rates of inactivation of four enzymes in raw buffalo milk were
      measured in relation to the process of heating to determine the value of these
      enzymes as markers for the evaluation of milk pasteurization. The activities of
      the enzymes alkaline phosphatase (ALP), lactic dehydrogenase (LDH), gamma
      glutamyltransferase (GGT), and aspartate aminotransferase (AST) were measured
      before and after heating at 50, 60, 70, and 80 degrees C for 1, 3, 5, 10, 20, and
      30 min. The enzyme GGT showed the highest activity (712 +/- 601 IU/liter),
      followed by LDH (386 +/- 183 IU/liter), ALP (295 +/- 164 IU/liter), and AST (18
      +/- 4 IU/liter). Heating the milk at 50 degrees C for 1 to 30 min resulted in no
      effect on the activity of any of the enzymes. At 60 degrees C, ALP showed the
      highest sensitivity to heat inactivation, whereas all other enzymes showed
      resistance. At 70 degrees C, ALP activity was abolished completely after 1 min,
      whereas GGT and LDH lost most activity after 10 min, and AST still maintained 50%
      activity even after 30 min. At 80 degrees C, the activities of LDH and GGT were
      lost, whereas AST still retained some of its activity. The results suggest that
      in addition to ALP, LDH and GGT, but not AST, are potential markers for heat
      denaturation in buffalo milk, with GGT having the advantage that its
      concentration is the highest.

PMID- 10914672
TI  - Survey of the furosine content in cheeses marketed in Spain.
AB  - The furosine content in 53 samples of different cheese types (fresh, ripened with
      molds, artisanal hard-pressed, industrial hard-pressed, and processed) marketed
      in Spain was analyzed. The lowest furosine values were observed in artisanal hard
      pressed cheeses (4.8 to 10.2 mg per 100 g of protein) and ripened with molds
      cheeses (4.2 to 12.8 mg per 100 g of protein). Industrial hard-pressed cheeses
      showed furosine values between 3.5 and 43.8 mg per 100 g of protein. Differences
      between samples may be attributed to the heat-treatment intensity given to cheese
      milk and to cheesemaking conditions. The highest contents of furosine were
      observed in processed cheeses (20 to 366.6 mg per 100 g of protein). A wide range
      of furosine content was found in fresh cheeses (17.9 to 73.6 mg per 100 g of
      protein), which could be due to the different amounts of dried milk added during
      the manufacture of cheeses.

PMID- 10914673
TI  - Kombucha, the fermented tea: microbiology, composition, and claimed health
      effects.
AB  - Kombucha is a slightly sweet, slightly acidic tea beverage consumed worldwide,
      but historically in China, Russia, and Germany. Kombucha is prepared by
      fermenting sweetened black tea preparations with a symbiotic culture of yeasts
      and bacteria. Potential health effects have created an increased interest in
      Kombucha. Yet, only a few research studies have shown that Kombucha has in vitro
      antimicrobial activity and enhances sleep and pain thresholds in rats.
      Furthermore, Kombucha consumption has proven to be harmful in several documented
      instances.

PMID- 10914674
TI  - Criteria to determine food allergen priority.
AB  - The emergent health issue of food allergens presents an important challenge to
      the food industry. More than 170 foods have been reported in the scientific
      literature as causing allergic reactions. Clearly, it would be impossible to deal
      with the presence of trace amounts of all these in the context of food labeling.
      If the decision to classify major allergens is based solely on the knowledge and
      experience of allergists and food scientists in the field, without scientifically
      defined criteria, it is likely to lead to a proliferation of lists. Such
      practices may lead to an unnecessary elimination of foods containing important
      nutrients. This paper defines food allergy, food intolerance, and food
      anaphylaxis and identifies criteria for classifying food allergens associated
      with frequent allergic reactions. A practical list of food allergens that may
      result in potentially life-threatening allergic reactions is provided. A
      mechanism-based (i.e., immunoglobulin E mediated), acute life-threatening
      anaphylaxis that is standardized and measurable and reflects the severity of
      health risk is proposed as the principal inclusion criterion for food allergen
      labeling. Where available, prevalence in the population and threshold levels of
      allergens should be used as an additional guide to identify possible future
      labeling needs.

PMID- 10914675
TI  - Genetic basis of acanthosis nigricans in Mexican Americans and its association
      with phenotypes related to type 2 diabetes.
AB  - Acanthosis nigricans (AN) is a skin condition associated with hyperinsulinemia
      and insulin resistance and has been shown to be a risk factor for type 2
      diabetes. The influence of genetic factors on AN and the basis of its association
      with type 2 diabetes and its risk factors are unknown. Using data from 397
      participants from two Mexican American family studies, we investigated the
      heritability of AN and its genetic correlation with other diabetes risk factors.
      AN was examined as both a continuous trait and a dichotomous trait by means of a
      previously described validated scale. The results indicated that the heritability
      (h2) for AN, when examined as a continuous trait, was high (0.58+/-0.10) and
      statistically significant (P<0.001). The h2 for AN as a dichotomous trait was
      estimated to be moderate (0.23+/-0.05) and was also significant (P=0.018). The
      additive genetic correlations between AN (either as a continuous trait or a
      dichotomous trait) and type 2 diabetes and its risk factors, including body mass
      index and fasting insulin, were high or moderately high and statistically
      significant. The random environmental correlations, by contrast, were low and
      statistically insignificant. These data suggest that genes that influence AN have
      pleiotropic effects on diabetes and its risk factors.

PMID- 10914676
TI  - Statistical and mutational analysis of chronic granulomatous disease in Japan
      with special reference to gp91-phox and p22-phox deficiency.
AB  - Chronic granulomatous disease (CGD) is a group of inherited disorders of host
      defense caused by a mutation in any of the four components of phagocyte NADPH
      oxidase, namely gp91-, p22-, p47-, and p67-phox. We have made a precise
      statistical analysis of 229 registered patients from 195 families in Japan and
      mutation analysis of 28 and 5 independent patients, respectively, with gp91- and
      p22-phox deficiency. The gp91- and p22-phox proteins form the membrane cytochrome
      b558, which plays important roles in the assembly of the active oxidase and
      electron-transfer reaction, and the lesions in either subunit account for more
      than 80% of cases. The ratio of male to female patients was 6.6/1, the incidence
      was calculated to be about 1 out of 220,000 birth, and the life expectancy of the
      patients born in the 1970s was estimated to be 25-30 years old. For the X-linked
      gp91-phox deficiency, we found five missense and nine nonsense mutations, seven
      deletions, three insertions, and four splice site mutations, which included the
      following novel mutations: four missense, five nonsense, six deletions, one
      insertion, and two splice site abnormalities. With regard to p22-phox deficiency,
      two homozygous nonsense mutations and one homozygous deletion, a missense
      mutation together with a splice site mutation, and two different missense
      mutations were found. These mutations have not been reported before. Based on the
      present and reported data from Japan, we discuss the molecular defects of the
      disease and the difference in statistics between western countries and Japan.

PMID- 10914677
TI  - The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal
      muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with
      Brody disease.
AB  - Brody disease is a rare inherited disorder of fast-twitch skeletal muscle
      function and is characterized by a lifelong history of exercise-induced
      impairment of skeletal muscle relaxation, stiffness, and cramps. The autosomal
      recessive inheritance of mutations in ATP2A1, the gene encoding SERCA1, which is
      the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, has been
      associated with Brody disease in three of six Brody families in which ATP2A1 has
      been sequenced. In the present analysis of the ATP2A1 gene in four unrelated
      families with autosomal recessive inheritance of Brody disease, three mutations
      were found in two families, leading to premature stop codons and truncated
      SERCA1. In a third family, the homozygous substitution of T for C2366 led to the
      missense mutation of Pro789 to Leu. The Pro789 to Leu mutant was readily
      expressed in HEK-293 cells, but it demonstrated an almost complete loss of Ca2+
      transport activity because of reduced Ca2+ affinity. In a fourth family, the
      heterozygous substitution of T for C2455, mutating Arg819 to Cys, was identified.
      This mutation was also readily expressed in HEK-293 cells and shown to have near
      normal Ca2+ transport activity, indicating that it is not causal for Brody
      disease. These results confirm the genetic heterogeneity of Brody disease and
      emphasize the importance of a functional test for mutant SERCA1; immunostaining
      of skeletal muscle to detect the loss of SERCA1a protein is not adequate for the
      diagnosis of ATP2A1-linked Brody disease.

PMID- 10914678
TI  - Splice-site mutation in TGM1 in congenital recessive ichthyosis in American
      families: molecular, genetic, genealogic, and clinical studies.
AB  - Lamellar ichthyosis (LI, OMIM no. 242300) is a severe autosomal recessive
      genodermatosis with an estimated prevalence of 1:200,000. LI represents one end
      of the spectrum of congenital recessive ichthyosis (CRI). Mutations in the gene
      for transglutaminase-1 (TGM1) are responsible for many cases of LI and occur
      throughout the coding sequence of the gene. Our analyses of patients with CRI
      revealed a common TGM1 mutation involving loss of the intron 5 splice acceptor
      site leading to alternative splicing of the message. We found families in which
      the splice acceptor site mutation was homozygous, and families where the patients
      were compound heterozygotes for the splice acceptor site mutation and another
      TGM1 mutation. A mutation at this same site occurs in the majority of Norwegian
      patients as a founder effect. In our ethnically diverse patient population, none
      of whom have known Norwegian ancestry, haplotype analysis of the TGM1 chromosomal
      region also suggested the existence of a founder effect. Comparison of the common
      haplotype in our data with the Norwegian data showed that 2/7 of our splice
      acceptor site mutation chromosomes had the full reported Norwegian haplotype, and
      the remaining five chromosomes exhibited recombination at the most distal marker
      studied. History, family origins, and haplotype analysis suggested that the
      mutation originally arose on a German background and was introduced into Norway
      around 800-1000 AD. We also found a limited correlation between genotype and
      phenotype in our study, with the four homozygous patients having less severe
      disease than many of the heterozygotes, and no patient with a splice acceptor
      site mutation having erythroderma or a congenital ichthyosiform erythroderma
      phenotype.

PMID- 10914679
TI  - Interchromosomal effects for chromosome 21 in carriers of structural chromosome
      reorganizations determined by fluorescence in situ hybridization on sperm nuclei.
AB  - We have used dual color fluorescence in situ hybridization (FISH) on decondensed
      sperm heads from four carriers of structural chromosome reorganizations, viz.
      t(3;15), t(Y;7), t(13;22) and inv(9), to assess the possible existence of an
      interchromosomal effect (ICE) on the segregation of chromosome 21. In the
      carriers of t(Y;7), t(13;22) and inv(9), all results were within the limits
      described in controls. A highly significant increase (P<0.0001) of disomy 21
      (1.90% v 0.37%), which could be considered as a positive ICE, was observed in the
      t(3;15) carrier. Significantly higher percentages (P<0.0001) of diploid sperm
      (5.71% v. 0.27%) were also observed in this patient. Our results suggests that
      the occurrence of an ICE may depend on the reorganization and on the chromosome
      and chromosome regions involved, resulting in a particular meiotic behaviour
      (presence of unsynapsed regions, preferential meiotic configurations) that could
      lead to the observed increase in chromosome 21 disomies. Further studies with
      this technical approach in a wide range of structural reorganizations could help
      to elucidate the actual occurrence of ICEs.

PMID- 10914680
TI  - Fine mapping of the constitutional translocation t(11;22)(q23;q11).
AB  - Translocation t(11;22)(q23;q11) is the most common constitutional reciprocal
      translocation in man. Balanced carriers are phenotypically normal, except for
      decreased fertility, an increased spontaneous abortion rate and a possible
      predisposition to breast cancer in some families. Here, we report the high
      resolution mapping of the t(11;22)(q23;q11) breakpoint. We have localised the
      breakpoint, by using fluorescence in situ hybidisation (FISH) walking, to a
      region between D11S1340 and WI-8564 on chromosome 11, and D22S134 and D22S264 on
      chromosome 22. We report the isolation of a bacterial artificial chromosome (BAC)
      clone spanning the breakpoint in 11q23. We have narrowed down the breakpoint to
      an 80-kb sequenced region on chromosome 11 and FISH analysis has revealed a
      variation of the breakpoint position between patients. In 22q11, we have
      sequenced two BACs (BAC2280L11 and BAC41C4) apparently mapping to the region;
      these contain low copy repeats (LCRs). Southern blot analysis with probes from
      BAC2280L11 has revealed different patterns between normal controls and
      translocation carriers, indicating that sequences similar/identical to these
      probes flank the translocation breakpoint. The occurrence of LCRs has previously
      been associated with genomic instability and "unclonable" regions. Hence, the
      presence of such repeats renders standard translocation breakpoint cloning
      techniques ineffective. Thus, we have used high resolution fiber-FISH to study
      this region in normal and translocation cases by using probes from 22q11, LCRs
      and 11q23. We demonstrate that the LCR containing the gap in 22q11 is probably
      substantially larger than the previous estimates of 100 kb. Using fiber-FISH, we
      have localised the breakpoint in 22q11 to approximately 20-40 kb from the
      centromeric border of the LCR (i.e. the telomeric end of AC006547) and have
      confirmed the breakpoint position on 11q23.

PMID- 10914681
TI  - Is there an interchromosomal effect in reciprocal translocation carriers? Sperm
      FISH studies.
AB  - Chromosome translocations have been known to affect disjunction of chromosomes
      unrelated to the translocation in the mouse and in Drosophila. However, in
      humans, an interchromosomal effect in chromosome translocations has not been
      demonstrated. The availability of techniques that allow the study of
      nondisjunction in sperm cells has permitted us to evaluate the possibility of an
      interchromosomal effect in male translocation heterozygotes. In this study,
      multicolor fluorescence in situ hybridization was used to determine levels of
      disomy for the clinically relevant chromosomes X, Y, 13, 18, and 21 in 332,858
      spermatozoa from nine reciprocal translocation heterozygotes and nine controls
      with normal karyotypes. The specific translocations studied were as follows:
      t(10;12)(p26.1;p13.3), t(2;18)(p21;q11.2), t(3;19)(p25;q12), t(5;8)(q33;q13),
      t(11;22)(q23;q11), t(3;4)(p25;p16), t(8;9) (q24.2;q32), t(10;18)(q24.1;p11.2),
      and t(4;10)(q33;p12.2). Comparisons of disomy rates between carriers and controls
      were performed by using the Mann-Whitney test. Our results showed that the rates
      of sex chromosome hyperhaploidy were similar in controls (0.21%) and in
      translocation carriers (0.19%). Similarly, the frequencies of disomy for
      chromosomes 13, 18, and 21 did not differ significantly between controls and
      carriers (0.05% versus 0.08%, 0.07% versus 0.03%, and 0.14% versus 0.20%,
      respectively). Sex chromosome nondisjunction was more common than nondisjunction
      of chromosomes 13 and 18 both in controls (P=0.0057) and in carriers (P=0.0008).
      Similarly, the rates of chromosome disomy for chromosome 21 were higher than
      those for chromosomes 13 and 18 in both controls (P=0.0031) and translocation
      carriers (P=0.0057). In our study, the excess of chromosome 21 disomy versus
      disomy of the other autosomes was more pronounced in carriers than in controls.
      Thus, although the difference of disomy 21 between controls and carriers was not
      statistically significant, it is worthy of attention.

PMID- 10914682
TI  - Variation in alphoid DNA size and trisomy 21: a possible cause of nondisjunction.
AB  - The cause of nondisjunction of chromosome 21 remains largely unknown. In the
      present report, we investigate the hypothesis that variation in alphoid DNA size
      has a role in trisomy formation. Pulsed-field gel electrophoresis was used to
      examine the chromosome 21 alphoid DNA array lengths in 23 families (all of
      Northern European ancestry) with an affected child with trisomy 21 in whom the
      parental and meiotic origin of nondisjunction had been determined as maternal
      meiosis I, and in 38 controls. Initially, the combined alphoid size of both
      chromosome 21 homologues was assessed. This indicated an association between
      small combined alphoid size and maternal meiosis I nondisjunction. Moreover, in a
      subset of the families under study (n=12), it was possible to study the alpha21-I
      size of individual chromosome 21 homologues (simple alphoid size); this provided
      further evidence that the risk for nondisjunction is related to the size of the
      alphoid array of one of the two chromosome 21 homologues being small.

PMID- 10914683
TI  - A 5-base insertion in the gammaC-crystallin gene is associated with autosomal
      dominant variable zonular pulverulent cataract.
AB  - A seven-generation family with 30 members affected by highly variable autosomal
      dominant zonular pulverulent cataracts has been previously described. We have
      localized the cataracts to a 19-cM interval on chromosome 2q33-q35 including the
      gamma-crystallin gene cluster. Maximum lod scores are 4.56 (theta=0.02) with
      D2S157, 3.66 (theta=0.12) with D2S72, and 3.57 (theta=0.052) with CRYG.
      Sequencing and allele-specific oligonucleotide analysis of the pseudo gammaE
      crystallin promoter region from individuals in the pedigree suggest that
      activation of the gammaE-crystallin pseudo gene is unlikely to cause the
      cataracts in the family. In addition, base changes in the TATA box but not the
      Sp1-binding site have been found in unaffected controls and can be excluded as a
      sole cause of cataracts. In order to investigate the underlying genetic mechanism
      of cataracts in this family further, exons of the highly expressed gammaC- and
      gammaD-crystallin genes have been sequenced. The gammaD-crystallin gene shows no
      abnormalities, but a 5-bp duplication within exon 2 of the gammaC-crystallin gene
      has been found in one allele of each affected family member and is absent from
      both unaffected family members and unaffected controls. This mutation disrupts
      the reading frame of the gammaC-crystallin coding sequence and is predicted to
      result in the synthesis of an unstable gammaC-crystallin with 38 amino acids of
      the first "Greek key" motif followed by 52 random amino acids. This finding
      suggests that the appropriate association of mutant betagamma-crystallins into
      oligomers is not necessary to cause cataracts and may give us new insights into
      the genetic mechanism of cataract formation.

PMID- 10914684
TI  - Multi-allelic origin of congenital disorder of glycosylation (CDG)-Ic.
AB  - Congenital disorders of glycosylation (CDG), formerly known as carbohydrate
      deficient glycoprotein syndrome, represent a family of genetic diseases with
      variable clinical presentations. Common to all types of CDG characterized to date
      is a defective Asn-linked glycosylation caused by enzymatic defects of N-glycan
      synthesis. Previously, we have identified a mutation in the ALG6 alpha1,3
      glucosyltransferase gene as the cause of CDG-Ic in four related patients. Here,
      we present the identification of seven additional cases of CDG-Ic among a group
      of 35 untyped CDG patients. Analysis of lipid-linked oligosaccharides in
      fibroblasts confirmed the accumulation of dolichyl pyrophosphate-Man9GlcNAc2 in
      the CDG-Ic patients. The genomic organization of the human ALG6 gene was
      determined, revealing 14 exons spread over 55 kb. By polymerase chain reaction
      amplification and sequencing of ALG6 exons, three mutations, in addition to the
      previously described A333 V substitution, were detected in CDG-Ic patients. The
      detrimental effect of these mutations on ALG6 activity was confirmed by
      complementation of alg6 yeast mutants. Haplotype analysis of CDG-Ic patients
      revealed a founder effect for the ALG6 allele bearing the A333 V mutation.
      Although more than 80% of CDG are type Ia, CDG-Ic may be the second most common
      form of the disease.

PMID- 10914685
TI  - Association of the low-density lipoprotein receptor gene with obesity in Native
      American populations.
AB  - Five low-density lipoprotein receptor gene (LDLR) restriction fragment length
      polymorphisms (RFLPs: TaqI, intron 4; HincII, exon 12; AvaII, exon 13; MspI and
      NcoI, exon 18) were investigated in 131 individuals from five Brazilian Indian
      tribes. All markers were polymorphic in this ethnic group. In the whole sample of
      Amerindians, 13 (41%) of the 32 expected haplotypes were identified, but only
      three were shared by all tribes. The Xavante, Surui, Zoro, and Gaviao tribes, who
      had been studied for anthropometry, were grouped according to their genotypes,
      and the corresponding mean values were examined. Significant associations were
      observed between HincII *H-, AvaII *A+, MspI *M-, and NcoI *N+ and the body mass
      index (BMI), triceps and subscapular skinfolds, and the arm fat index (AFI).
      Haplotypes were derived for these four RFLPs, and (*H-/*A+/*M-/*N+) haplotype
      carriers were compared with noncarriers of this haplotype with equally
      significant results for the three parameters (BMI, P=0.021; skinfold thickness,
      P<0.001; AFI, P=0.005). These results suggest that the LDLR gene has some
      influence over adipose tissue deposition.

PMID- 10914686
TI  - A genetic study of Hodgkin's lymphoma: an estimate of heritability and
      anticipation based on the familial cancer database in Sweden.
AB  - Hodgkin's lymphoma (HL) is a heterogeneous hemopoietic malignancy. Previous
      studies have implicated a genetic etiology responsible for familial HL. We have
      estimated the heritability of HL and tested the hypothesis of genetic
      anticipation by using a high quality cancer database of the Swedish population.
      Heritability was estimated by employing a threshold-liability model. To test the
      hypothesis of anticipation, the usual T-test procedure was used to test whether
      there was a difference in cancer age-of-onset between parents and children who
      were affected with HL. A randomization test was carried out to test the validity
      of the P-values. Additional analyses were performed after stratifying the data
      based on birth cohorts. This data set revealed that there was a difference
      between the age-of-onset of parents and of offspring who were affected with HL.
      We also estimated the heritability of HL in the Swedish population to be
      approximately 28.4%. Both findings provide further evidence for a genetic basis
      for HL.

PMID- 10914687
TI  - Autosomal dominant macrothrombocytopenia with leukocyte inclusions (May-Hegglin
      anomaly) is linked to chromosome 22q12-13.
AB  - Macrothrombocytopenia with leukocyte inclusions (May-Hegglin anomaly) is a rare
      autosomal dominant disorder characterized by thrombocytopenia, giant platelets,
      and Dohle body-like inclusions in leukocytes. To determine the genetic basis of
      this disorder, we performed a genome-wide screen for linkage in three families
      with May-Hegglin anomaly. For the pooled analysis of the three families, three
      markers on chromosome 22 had two-point logarithm-of-difference (lod) scores
      greater than 3, with a maximum lod score of 3.91 at a recombination fraction
      (theta) of 0.076 for marker D22S683. Within the largest family (MHA-1), the
      maximum lod score was 5.36 at theta=0 at marker D22S445. Fine mapping of
      recombination events using eight adjacent markers indicated that the minimal
      disease region of family MHA-1 alone is in the approximately 26 cM region from
      D22S683 to the telomere. The maximum lod score for the three families combined
      was 5.84 at theta=0 for marker IL2RB. With the assumption of locus homogeneity,
      haplotype analysis of family MHA-4 indicated the disease region is centromeric to
      marker D22S1045. These data best support a minimal disease region from D22S683 to
      D22S1045, a span of about 1 Mb of DNA that contains 17 known genes and 4
      predicted genes. Further analysis of this region will identify the genetic basis
      of May-Hegglin anomaly, facilitating subsequent characterization of the
      biochemical role of the disease gene in platelet formation.

PMID- 10914688
TI  - Analysis of genetic polymorphisms in the transforming growth factor-beta1 gene
      and the risk of Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a complex disease involving several genetic and
      environmental components. Genetic studies have yet to identify all the genes
      involved in the pathogenesis of AD. Transforming growth factor-beta1 (TGF-beta1)
      is a candidate gene for AD. It is a multifunctional cytokine whose overexpression
      has been shown to promote the deposition of amyloid-beta peptide. The goal of
      this study was to investigate the association of three polymorphisms in TGF-beta1
      with the risk of AD. Two of the polymorphisms are located in the 5' region at
      positions -800 (G-->A) and -509 (C-->T), and the third is in exon 5 at codon 263
      (Thr-->Ile). We screened DNA samples from 428 sporadic, late-onset patients and
      421 controls by PCR-based assays. There was no statistically significant
      difference in genotype or allele frequency distributions between cases and
      controls for the -800 or codon 263 polymorphisms (P=0.38 and P=0.60,
      respectively). The overall genotype distribution at the -509 site was
      significantly different between cases and controls. (P=0.017). The frequency of
      the -509/TT genotype was significantly higher in AD patients than controls
      (P=0.015). We further tested whether this polymorphism may alter the regulation
      of the TGF-beta1 gene using dual luciferase reporter assay. We subcloned the 5'
      flanking region, which contained the -509 C/T polymorphic sites, in front of the
      firefly luciferase reporter gene in pGL-3 basic vector and co-transfected with
      the pRL-CMV vector containing Renilla luciferase gene as a control for
      transfection efficiency in COS-1 cells. The activity of each promoter allele was
      directly measured by the ratio of firefly luciferase activity to Renilla
      luciferase activity. The -509 T allele was associated with marginally higher
      transcriptional activity of TGF-beta compared with the -509 C allele (P=0.051).
      These data suggest that the -509 polymorphism of TGF-beta1 may be modestly
      associated with the risk of AD. However, these data should be interpreted with
      caution as the differences associated with the -509 alleles in both the genetic
      association and the transfection studies were modest.

PMID- 10914689
TI  - Calcium and magnesium in drinking water and the risk of death from breast cancer.
AB  - The relationship between mortality from breast cancer and the levels of calcium
      and magnesium in drinking water was examined using an ecological design. The
      study area consisted of 2.52 municipalities in Taiwan. Data on the levels of
      calcium and magnesium in drinking water were collected from the Taiwan Water
      Supply Corporation (TWSC). The age-standardized mortality rate (ASR) for breast
      cancer ( 1982-1991) was compared among municipalities with different levels of
      magnesium and calcium in drinking water. Weighted multivariate regression
      analysis was used, and after adjusting for fertility rates and urbanization,
      there was a significant inverse relationship between the levels of calcium and
      magnesium in drinking water and risk of death from breast cancer.

PMID- 10914691
TI  - Contribution of nitrosobenzene to splenic toxicity of aniline.
AB  - To elucidate the mechanism(s) of splenic toxicity of aniline, studies were
      conducted with nitrosobenzene (NB), an N-oxidized metabolite of aniline. Male
      Sprague-Dawley rats were given 0.025, 0.05, 0.1, or 0.2 mmol/kg/d of NB in 0.5 ml
      of 0.25% agar by gavage for 4 d; control rats received the vehicle only. Animals
      were euthanized at 24 h following the last dose. NB treatment resulted in
      decreased erythrocyte counts, whereas methemoglobin content increased at 0.1- and
      0.2-mmol/kg doses. Spleen weight to body weight ratios were greater by 55 and 81%
      at O.1- and 0.2-mmol/kg NB doses, respectively. Total iron content in the spleens
      of NB-treated rats showed dose-dependent significant increases, and the nonheme
      iron followed a similar pattern. Splenic lipid peroxidation showed a dose
      dependent response and was greater by 19, 56, 74, and 85% at the 4 doses,
      respectively. Malondialdehyde (MDA)-protein adducts, as quantitated by a
      competitive enzyme-linked immunosorbent assay (ELISA), were markedly greater in
      all the NB-treated groups, with the highest increase of 248% at 0.2 mmol/kg.
      Furthermore, NB exposure also resulted in greater protein oxidation (carbonyl
      content) in the spleens at 0.1- and 0.2-mmol/kg doses. These results suggest that
      NB is a splenotoxin and therefore can contribute to the splenic toxicity of
      aniline. Results of this study further support our earlier findings that
      oxidative stress is a potential mechanism in the splenotoxicity of aniline.

PMID- 10914690
TI  - Metals and metallothionein in the liver of raccoons: utility for environmental
      assessment and monitoring.
AB  - The relationship between metallothionein levels and concentrations of several
      metals and radionuclides was examined in liver tissues of raccoons (Procyon
      lotor, n = 47) from the Department of Energy's Savannah River Site in South
      Carolina to determine the applicability of metallothioneins as an initial
      screening device for exposure assessment in free-living mammals and environmental
      monitoring. Using a fluorescent marker and a cell sorter to measure
      metallothionein, a significant positive correlation was found across animals
      between levels of metallothioneins and concentrations of selenium (Pearson's r =
      .30), mercury (Pearson's r = .3 1), and copper (Pearson's r = .30) in liver
      tissue. Arsenic, cobalt, silver, thallium, and tin were below detection limits in
      most or all liver samples. Other metals, including cadmium, chromium, radiocesium
      (137-Cs), copper, lead, manganese, strontium, and vanadium, showed only weak and
      nonsignificant correlations with metallothionein. Concentrations of mercury were
      correlated with concentrations of selenium (Pearson's r = .73), manganese
      (Pearson's r = .56), and strontium (Pearson's r = .57). In an a posteriori test,
      there was a still unexplained positive correlation between mercury (Pearson r =
      .56), selenium (Pearson r = .54), and radiocesium (Pearson's r = .38)
      concentrations and background cellular autofluorescence, and a negative
      correlation of strontium with the latter (Kendall tau = -.38). Background
      cellular autofluorescence may represent a generalized cellular stress response,
      or a yet unidentified biomarker. To better understand which metals contribute to
      the induction of metallothionein, principle component analysis (PCA) was
      performed. The first three principle components explained 78% of the variance,
      with highest loadings being from mercury and radiocesium. Metallothionein levels
      did not correlate well with the principal components from the metals and
      radiocesium, while autofluorescent background levels tended to correlate better.

PMID- 10914692
TI  - Dieldrin induces cytosolic [3H]7, 12-dimethylbenz[a]anthracene binding but not
      multidrug resistance proteins in rainbow trout liver.
AB  - Previously it was demonstrated that biliary excretion of a single dose of
      [14C]dieldrin or [3H]7, 12-dimethylbenz/alanthracene (DMBA) was stimulated up to
      700% and 300%, respectively, in rainbow trout fed 0.3-0.4 mg dieldrin/kg/d for 9
      12 wk. This was not explained by increased activities of hepatic microsomal
      xenobiotic-metabolizing enzymes or increased amounts of any of six cytochrome P
      450 isozymes quantitated by Western blots. It was hypothesized that stimulated
      excretion was explained by induction of (1) cytosolic binding proteins that
      facilitated intracellular trafficking of DMBA to sites of metabolism, or (2) ATP
      dependent proteins that transport xenobiotic metabolites from liver to bile.
      Binding of 15 and 60 nmol [3H]DMBA/mg protein increased about 200% in hepatic
      cytosol from dieldrin-fed fish. A 50-fold molar excess of unlabeled DMBA reduced
      binding of 15 nmol [3H]DMBA/mg protein (nonspecific binding) by the same amount
      in cytosol from control and dieldrin-fed fish, indicating that dieldrin induced
      specific binding. Liver sections from control and dieldrin-fed fish were treated
      with multidrug resistance (MDR) protein monoclonal antibodies C494, C219, and JSB
      1, and polyclonal antibody MDR Ab-1. There were no marked differences in optical
      densities of immunohistochemical staining near bile canaliculi of control and
      dieldrin-fed fish. Induction of xenobiotic binding capacity in cytosol of
      dieldrin-fed rainbow trout at least partially explained altered DMBA disposition
      in fish pretreated with this cyclodiene insecticide.

PMID- 10914693
TI  - Changes in egg composition of American kestrels exposed to dietary
      polychlorinated biphenyls.
AB  - Changes in the quality of eggs of birds exposed to polychlorinated biphenyls
      (PCBs) have been described, but have never been directly attributed to PCBs.
      Polychlorinated biphenyl residues in eggs have been associated with reduced
      reproductive success and embryonic deformities in wild birds. Egg size and
      composition, specifically the amount of albumen, yolk, and water in an egg, also
      influence the growth and viability of embryos and hatchlings, and consequently
      the reproductive success of birds. To deter mine whether PCB exposure of adult
      birds affected the size and composition of their eggs, 25 pairs of captive
      American kestrels (Falco sparverius) were fed a mixture of PCB-spiked
      (1248:1254:1260) food to give an approximate exposure of 7 mg/kg body weight/d,
      beginning 1 mo prior to pairing, and continuing throughout the courtship, egg
      laying, and incubation periods. This dietary level in the adult female kestrels
      resulted in mean total PCB residues in the eggs of 34.1 microg/g wet weight
      (geometric mean), which is environmentally relevant. PCB residues in eggs
      increased with the time of female exposure to the contaminated diet and laying
      date. Variation in egg size within PCB clutches was significantly greater than
      within control clutches, although absolute egg mass and volume did not differ
      markedly by treatment. Only infertile eggs and only one egg per clutch were used
      for egg composition analysis. Yolks in the PCB-contaminated eggs were heavier,
      with less wet and dry albumen relative to control eggs. Water content and
      eggshell thickness were not significantly affected by PCB exposure. These results
      suggest that eggs from the PCB treatment have relatively more lipid and less
      protein available for embryonic development. Changes in egg composition were not
      associated with egg size, lay date, ambient temperature, humidity, or
      precipitation, which are factors known to affect these variables in bird eggs.
      The PCB-induced changes in egg composition described here provide insight into
      possible mechanisms contributing to reduced reproductive performance in wild
      birds exposed to PCBs.

PMID- 10914694
TI  - COX-2 specific inhibitors in the management of arthritis and pain. Introduction.

PMID- 10914695
TI  - COX-2 specific inhibitors offer improved advantages over traditional NSAIDs.
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely
      prescribed medications worldwide and are often the first choice of treatment for
      acute myalgias, orthopedic injuries, postoperative pain, chronic rheumatoid
      arthritis, and osteoarthritis. The mechanism through which NSAIDs provide
      analgesia and suppress inflammation is the inhibition of the enzyme
      cyclooxygenase, resulting in decreased prostaglandin synthesis. The suppression
      of prostaglandin synthesis can also produce gastric and renal toxicity, as well
      as impair normal platelet function. Thus, NSAIDs are associated with potentially
      harmful side effects. Cyclooxygenase exists in two isoenzymatic forms,
      cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Cyclooxygenase-1 appears
      to be constitutively expressed in many tissues and produces prostaglandins, which
      regulate normal cellular functions. However, COX-2 activity is induced by
      proinflammatory cytokines and produces prostaglandins that mediate the
      inflammatory response and pain signaling transmission. Traditional nonspecific
      NSAIDs inhibit both COX-1 and COX-2, and in doing so, not only decrease
      inflammation and pain, but also promote gastrointestinal tract damage and
      bleeding. The potential clinical benefit of COX-2 inhibitors is significant due
      to the number of patients chronically treated with NSAIDs and the three- to ten
      fold higher risk of gastrointestinal injury and death associated with traditional
      NSAIDs. Recently, a class of anti-inflammatory medications has been developed
      that primarily inhibits COX-2 while sparing the enzymatic activity of COX-1 at
      therapeutic dosages. Two medications that predominantly inhibit only COX-2,
      rofecoxib and celecoxib, are currently available by prescription in the United
      States.

PMID- 10914696
TI  - Use of COX-2 specific inhibitors in operative and nonoperative management of
      patients with arthritis.
AB  - Arthritis is a major burden on society and the individual. Arthritis affects all
      age groups and races, and is more prevalent in women than men by approximately
      1.65:1. Nearly one half of people aged > or = 65 years report the presence of
      arthritic symptoms; however, by no means is arthritis a disease of only the
      elderly. The burden of arthritis will continue to increase due to expected future
      increases in the size and age of the general population. Currently, the total
      costs of medical care and lost wages due to arthritis are in excess of 64 billion
      dollars per year in the United States. For the individual, arthritis may cause
      substantial pain, impair mobility, curtail physical activity, and have a negative
      impact on mental health. The two most common forms of arthritis, osteoarthritis
      and rheumatoid arthritis, have major health complications. From the perspective
      of the orthopedic surgeon, the aim of treatment of arthritic conditions includes
      early, accurate diagnosis and appropriate treatment to minimize pain and maximize
      function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as
      part of the medical management of patients with arthritis. These medications are
      effective in mitigating pain and inflammation associated with arthritis. However,
      side effects (most notably of the gastrointestinal tract) have limited the more
      widespread use of NSAIDs. The newer cyclooxygenase-2 (COX-2) inhibitors have
      proven to be efficacious and have demonstrated fewer gastrointestinal adverse
      effects. Furthermore, COX-2 inhibitors do not appear to adversely affect platelet
      function. For these reasons, consideration may be given to using COX-2
      perioperatively, however, drug interactions must be closely monitored.

PMID- 10914697
TI  - Current concepts in sports medicine: the use of COX-2 specific inhibitors and the
      emerging trends in arthroscopic surgery.
AB  - Arthritis does not escape the athlete. From the recreational athlete to the
      professional athlete, arthritis can be a common and perplexing problem. In the
      typical orthopedic sports medicine practice, it is no longer uncommon to see
      relatively young patients suffering from arthritis. It can affect the major
      joints such as the knee, hip, ankle, shoulder, and elbow. One of the most common
      problems is shoulder arthritis secondary to injury in recreational athletes.
      Athletes at risk for shoulder arthritis typically include overhead athletes and
      weight lifters. The clinical presentation is usually specific for pain, decreased
      range of motion, and sometimes mechanical symptoms. Physical examination reveals
      a loss of motion, crepitus, catching, and locking; often, there is associated
      underlying instability. Radiographs can confirm the diagnosis of glenohumeral
      degenerative arthritis. Pain control is a primary objective when treating these
      athletes with arthritis at any level. Cyclooxygenase-2 (COX-2) specific
      inhibitors are emerging as primary treatment because of their anti-inflammatory
      and analgesic effect. Although a nonsteroidal anti-inflammatory drugs, COX-2
      inhibitors block the enzymes that trigger pain and inflammation, while sparing a
      related enzyme that helps maintain the normal stomach lining (cyclooxygenase-1).
      In contrast, traditional nonsteroidal anti-inflammatory drugs block both enzymes
      and may cause damage to the stomach lining, potentially leading to ulcers.
      Minimally invasive surgery can be performed as a palliative procedure for
      treating early arthritis in athletes. These procedures include removal of loose
      bodies, debridement, capsular release, and other associated procedures such as
      rotator cuff repair and decompression. Rehabilitation plays an important role in
      nonoperative treatment and also an important role in postoperative treatment
      particularly to restore motion. Modification of activities continues to be an
      important adjunct in managing these types of arthritic problems in relatively
      young athletes.

PMID- 10914698
TI  - Temozolomide and treatment of malignant glioma.
AB  - Malignant gliomas (glioblastoma multiforme and anaplastic astrocytoma) occur more
      frequently than other types of primary central nervous system tumors, having a
      combined incidence of 5-8/100,000 population. Even with aggressive treatment
      using surgery, radiation, and chemotherapy, median reported survival is less than
      1 year. Temozolomide, a new drug, has shown promise in treating malignant gliomas
      and other difficult-to-treat tumors. Temozolomide, a p.o. imidazotetrazine second
      generation alkylating agent, is the leading compound in a new class of
      chemotherapeutic agents that enter the cerebrospinal fluid and do not require
      hepatic metabolism for activation. In vitro, temozolomide has demonstrated
      schedule-dependent antitumor activity against highly resistant malignancies,
      including high-grade glioma. In clinical studies, temozolomide consistently
      demonstrates reproducible linear pharmacokinetics with approximately 100% p.o.
      bioavailability, noncumulative minimal myelosuppression that is rapidly
      reversible, and activity against a variety of solid tumors in both children and
      adults. Preclinical studies have evaluated the combination of temozolomide with
      other alkylating agents and inhibitors of the DNA repair protein O6-alkylguanine
      alkyltransferase to overcome resistance to chemotherapy in malignant glioma and
      malignant metastatic melanoma. Temozolomide has recently been approved in the
      United States for the treatment of adult patients with refractory anaplastic
      astrocytoma and, in the European Union, for treatment of glioblastoma multiforme
      showing progression or recurrence after standard therapy. Predictable
      bioavailability and minimal toxicity make temozolomide a candidate for a wide
      range of clinical testing to evaluate the potential of combination treatments in
      different tumor types. An overview of the mechanism of action of temozolomide and
      a summary of results from clinical trials in malignant glioma are presented here.

PMID- 10914699
TI  - Role of intestinal P-glycoprotein in the plasma and fecal disposition of
      docetaxel in humans.
AB  - Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein
      that is abundantly present in biliary ductal cells and epithelial cells lining
      the gastrointestinal tract. Here, we have determined the role of P-gp in the
      metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans.
      Pharmacokinetic profiles were evaluated in five cancer patients receiving
      treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in
      combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg
      b.i.d.). The terminal disposition half-life and total plasma clearance of
      docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The
      cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47
      +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in
      the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4
      mediated metabolites of docetaxel in feces were significantly increased after
      combination treatment with R101933 (P = 0.010), indicating very prominent and
      efficient detoxification of reabsorbed docetaxel into hydroxylated compounds
      before reaching the systemic circulation. It is concluded that intestinal P-gp
      plays a principal role in the fecal elimination of docetaxel by modulating
      reabsorption of the drug after hepatobiliary secretion. In addition, the results
      indicate that inhibition of P-gp activity in normal tissues by effective
      modulators, and the physiological and pharmacological consequences of this
      treatment, cannot be predicted based on plasma drug monitoring alone.

PMID- 10914700
TI  - Molecular changes in the bronchial epithelium of patients with small cell lung
      cancer.
AB  - To better understand the pathways involved in the pathogenesis of small cell lung
      carcinoma (SCLC), we compared the patterns of molecular changes present in these
      tumors and their accompanying bronchial epithelium with those present in the
      other two major types of lung cancer [squamous cell carcinoma (SQC) and
      adenocarcinoma (ADC)]. We obtained DNA from 68 microdissected invasive lung
      tumors (22 SCLCs, 21 ADCs, and, 25 SQCs) and 119 noncontiguous foci of
      histologically normal or hyperplastic epithelia from 10 tumors of each
      histological type. We determined loss of heterozygosity and microsatellite
      alterations at 12 chromosomal regions frequently deleted in lung cancers using 19
      polymorphic microsatellite markers. Our major findings are as follows: (a) the
      mean index of allelic loss in SCLC (0.85) and SQC (0.71) tumors was higher than
      that in ADC (0.39) tumors; (b) although there was considerable overlap, each
      tumor type had a characteristic pattern of allelic loss; (c) most samples of
      bronchial epithelium accompanying SCLC (90%) had allelic loss at one or more loci
      compared with samples accompanying SQC (54%) or ADC (10%); (d) the mean index of
      allelic loss was much higher in bronchial epithelial samples from SCLC (0.27)
      than in those from SQC (0.08) or ADC (0.01); and (e) although the mean indices of
      microsatellite alterations in the tumor types were similar, the bronchial
      epithelial samples accompanying SCLC had a 10-fold higher mean index (0.063) than
      those accompanying SQC (0.006) or ADC (0.006). Our findings indicate that
      extensive genetic damage in the accompanying normal and hyperplastic bronchial
      epithelium is characteristic of SCLC tumors and suggest major differences in the
      pathogenesis of the three major lung cancer types.

PMID- 10914701
TI  - Intranodal antitumor immunocyte infiltration in node-negative gastric cancers.
AB  - The status and role of immunocytes and dendritic cells in regional lymph nodes in
      patients with gastric cancer are examined in this study. Forty-nine patients with
      gastric cancer who underwent curative resection were enrolled in the present
      study. These patients had no lymph node metastases according to a histological
      examination. The infiltration of natural killer (NK) cells, dendritic cells, and
      MIB-1-positive immunocytes was investigated. Based on the Japanese Classification
      of Gastric Carcinoma, regional lymph nodes were divided into three compartments:
      (a) compartment 1 (lymph node station numbers 1-6); (b) compartment 2 (lymph node
      station numbers 7-12); and (c) compartment 3 (lymph node station numbers 14 and
      16). Dendritic cells and MIB-1-positive immunocytes infiltrated compartment 1
      lymph nodes in increased numbers compared with the lymph nodes of compartments 2
      or 3 (P < 0.05). Conversely, intranodal NK cell infiltration did not differ
      significantly among the three compartments. The incidence of intranodal dendritic
      and MIB-1-positive cell infiltration in patients with submucosal gastric cancer
      was significantly higher than in patients with tumors that invaded beyond the
      muscularis propria. The decreased expression of these immunological markers
      correlated well with recurrent disease, regardless of tumor depth. The immunocyte
      level is higher in lymph nodes near the primary tumor (compartment 1) than in
      those that are distant from the tumor (compartments 2 and 3). This pertains to
      all three markers, i.e., NK, dendritic, and MIB-1-positive cells. Unlike
      dendritic and MIB-1-positive cells, intratumoral infiltration of NK cells did not
      correlate well with either lymph node compartment or the depth of tumor invasion.
      The degree of NK cell infiltration may be directly associated with antitumor
      effects, especially in compartment 1. A decrease in all three markers is
      associated with tumor recurrence.

PMID- 10914702
TI  - Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4.
AB  - We have identified previously six nuclear matrix proteins (NMPs) that are bladder
      cancer specific. In this study, we analyzed the expression of one of these
      proteins, BLCA-4, in bladder tumors and normal bladder tissue. We also examined
      the appearance of BLCA-4 in the urine as a biomarker for bladder cancer. BLCA-4
      was isolated from nuclear matrix preparations of bladder tumors, and its peptide
      sequence was determined. The antibodies generated against the resulting BLCA-4
      peptides were then used to detect its presence in immunoblots and in urine
      samples by immunoassay. We analyzed tissue samples of bladder tumor and normal
      donor bladders and urine obtained from 51 normal individuals and 54 patients with
      pathologically confirmed bladder cancer. The BLCA-4 peptide sequences do not
      resemble any known human protein sequences. On immunoblot analysis, BLCA-4
      expression was detectable in tumor and normal tissues from patients with bladder
      cancer but not in any of the normal bladder tissue obtained from organ donors.
      Using a prospectively determined cutoff level of 13 A (absorbance) units/microg
      protein, all 51 normal individuals tested were negative for BLCA-4 expression,
      whereas 53 of 55 samples from patients with bladder cancer were positive. These
      results suggest that BLCA-4 is present throughout the bladder in both the tumor
      and morphologically normal areas in bladder cancer patients. BLCA-4 is a very
      sensitive (96.4%) and specific (100%) marker for bladder cancer. BLCA-4 is a
      bladder cancer-specific marker that can be detected using a urine-based assay and
      can be used in the diagnosis of bladder cancer.

PMID- 10914703
TI  - BBR 3464: a novel triplatinum complex, exhibiting a preclinical profile of
      antitumor efficacy different from cisplatin.
AB  - Multinuclear platinum complexes represent a new class of anticancer agents,
      distinct in terms of DNA binding features and the profile of antitumor activity
      from their mononuclear counterparts, in particular cisplatin. Among complexes of
      this class, BBR 3464, a trinuclear platinum compound has been selected for
      preclinical development. In the present study, we describe the preclinical
      evaluation of BBR 3464 in a series of human tumor cell lines and tumor
      xenografts, with special emphasis on tumor types known to be resistant to
      cisplatin. In a panel of seven human tumor cell lines naturally resistant to
      cisplatin (three ovarian and four melanomas), BBR 3464 was extremely potent with
      IC50 values at least 20-fold lower than cisplatin. Against eight human tumor
      xenografts including four tumors refractory to cisplatin, BBR 3464 was confirmed
      to be very active with a tumor weight inhibition >80% in seven of them. The
      efficacy of BBR 3464 against cisplatin-resistant tumors was consistent with the
      ability of the drug to completely overcome resistance in three cell systems
      characterized by acquired resistance to cisplatin. Moreover, BBR 3464 caused a
      more prolonged effect than cisplatin, which was reflected by higher specific
      growth delay values. This prolonged effect is likely to be related to a more
      persistent perturbation of the cell cycle induced by BBR 3464 than by cisplatin,
      as shown in one ovarian tumor cell line. Finally, the profile of sensitivity to
      BBR 3464 within the 60-cell-lines screening panel of the National Cancer
      Institute, NIH (Bethesda, MD) differed from those of established drugs, thus
      supporting the hypothesis of a distinct mechanism of cytotoxic activity of BBR
      3464. The novel trinuclear platinum complex, in light of its innovative antitumor
      activity profile, has the potential to become a useful clinical agent for the
      treatment of unresponsive tumors.

PMID- 10914704
TI  - Treatment of human metastatic transitional cell carcinoma of the bladder in a
      murine model with the anti-vascular endothelial growth factor receptor monoclonal
      antibody DC101 and paclitaxel.
AB  - Vascular endothelial cell growth factor (VEGF) regulates angiogenesis and
      metastasis of bladder cancer (transitional cell carcinoma, TCC) through binding
      to VEGF receptor-2 (VEGFR-2). In this study, we evaluated whether the anti-VEGFR
      monoclonal antibody (Mab) DC101 in combination with paclitaxel inhibited
      tumorigenesis, angiogenesis, and metastasis of human TCC growing within the
      bladder of athymic nude mice. In vivo therapy with Mab DC101 and paclitaxel
      induced significant regression of bladder tumors compared with either agent
      alone. Median bladder weights were reduced from 601 mg in untreated controls, 422
      mg in mice treated with paclitaxel alone (P < 0.005), 361 mg in mice treated with
      DC101 alone (P < 0.005), and 113 mg in mice that received combination therapy (P
      < 0.0005). Only one of nine mice developed spontaneous lymph node metastasis
      after combined treatment, compared with seven of seven untreated controls (P <
      0.0005), six of eight after DC101 (P < 0.01), and five of eight mice after
      paclitaxel (P < 0.05). Combined treatment with both paclitaxel and DC101
      inhibited tumor-induced neovascularity compared with all other groups (P <
      0.005), without altering the expression of VEGF or flk1. Mab DC101 and paclitaxel
      combined enhanced apoptosis in the tumor and endothelial cells compared with
      other treatment (P < 0.005). These studies indicate that Mab DC101, which blocks
      VEGFR-2 function, has significant efficacy against human TCC, especially when
      combined with the chemotherapeutic agent paclitaxel. The antitumor effect was
      mediated by inhibition of angiogenesis and induction of both tumor cell and
      endothelial cell apoptosis.

PMID- 10914705
TI  - Combination immunotherapy of relapsed or refractory low-grade or follicular non
      Hodgkin's lymphoma with rituximab and interferon-alpha-2a.
AB  - Rituximab and IFN have each demonstrated single-agent activity in patients with
      low-grade non-Hodgkin's lymphoma (NHL). A single-arm, multicenter, Phase II trial
      was conducted to assess the safety and efficacy of combination therapy with
      rituximab and IFN-alpha-2a in 38 patients with relapsed or refractory, low-grade
      or follicular, B-cell NHL. IFN-alpha-2a [2.5 or 5 million units (MIU)] was
      administered s.c., three times weekly for 12 weeks. Starting on the fifth week of
      treatment, rituximab was administered by i.v. infusion (375 mg/m2) weekly for 4
      doses. All 38 patients received four complete infusions of rituximab and were
      evaluable for efficacy, although 11 patients (29%) did not-receive all 36
      injections of IFN. The mean number of IFN-alpha-2a injections was 31 doses; the
      mean total units received were 141 MIU (maximum, 180 MIU). The study treatment
      was reasonably well tolerated with no unexpected toxicities stemming from the
      combination therapy. No grade 4 events were reported. Frequent adverse events
      during the treatment period included asthenia (35 of 38 patients), chills (31 of
      38), fever (30 of 38), headache (28 of 38), nausea (23 of 38), and myalgia (22 of
      38). The overall response rate was 45% (17 of 38 patients); 11% had a complete
      response, and 34% had a partial response. The Kaplan-Meier estimates for the
      median response duration and the median time to progression in responders are
      22.3 and 25.2 months, respectively. Further follow-up is needed to determine
      whether this treatment combination leads to a significantly longer time to
      progression than single-agent treatment with rituximab.

PMID- 10914706
TI  - Induction of Ab3 and Ab3' antibody was associated with long-term survival after
      anti-G(D2) antibody therapy of stage 4 neuroblastoma.
AB  - Treatment with anti-G(D2) monoclonal antibody 3F8 (Ab1) at the time of remission
      may prolong survival for children with stage 4 neuroblastoma. A transient human
      antimouse antibody (HAMA) response was associated with significantly longer
      survival (Cheung et al., J. Clin. Oncol., 16: 3053-3060, 1998). Because this
      response was primarily anti-idiotypic (Ab2), we postulate that the subsequent
      induction of an idiotype network that included an elevation of anti-anti
      idiotypic (Ab3) and anti-G(D2) (Ab3') antibody titers may be responsible for
      tumor control. Thirty-four patients with stage 4 neuroblastoma diagnosed at >1
      year of age were treated with 3F8 at the end of chemotherapy. Most had either
      bone marrow (31 of 34) or distant bony (29 of 34) metastases at diagnosis.
      Thirteen patients were treated at second or subsequent remission, and 12 patients
      in this group had a history of progressive/persistent disease after bone marrow
      transplantation; 21 patients were treated in the first remission after N6
      chemotherapy. Their serum HAMA, Ab3, and Ab3' titers prior to, at 6, and at 14
      months after antibody treatment were measured by ELISA. Among these 34 patients,
      14 are alive, and 13 (1.8-7.4 years at diagnosis) are progression free (53-143
      months from the initiation of 3F8 treatment) without further systemic therapy.
      Long-term progression-free survival (PFS) and survival correlated significantly
      with Ab3' (anti-G(D2)) response at 6 months and with Ab3 response at 6 and 14
      months. By defining Ab3 threshold ranging from the ratio of 1.1 to 2.6 above
      pretreatment level, the difference in PFS and survival between the high-Ab3 and
      low-Ab3 groups became markedly widened. Similarly, increasing the Ab3' threshold
      at either 6 or 14 months to 300% above pre-3F8 levels also increased the spread
      between the high versus low Ab3' groups for both PFS and survival curves. Non
      idiotype antibody responses (anti-mouse-IgG3 or anti-tumor nuclear HUD antigen)
      had no apparent impact on PFS or survival. In conclusion, despite the high-risk
      nature of stage 4 neuroblastoma, long-term remission without myeloablative
      therapy can be achieved with 3F8 treatment. Ab3 and Ab3' antibody response
      correlated with prolonged PFS and survival. We postulate that successful
      induction of an idiotype network in patients may be responsible for long-term
      tumor control.

PMID- 10914707
TI  - A dose-escalation and pharmacokinetic study of subcutaneously administered
      recombinant human interleukin 12 and its biological effects in Japanese patients
      with advanced malignancies.
AB  - A pilot dose-escalation study of recombinant human interleukin 12 (rhIL-12) was
      conducted in Japanese patients with advanced malignancies. Cohorts of three
      patients received escalating doses of rhIL-12 that increased from 50 to 300
      ng/kg/day s.c. three times a week for 2 weeks followed by 1-week rest. The same
      dosage and schedule was repeated for two additional courses. Sixteen previously
      treated patients were registered, and 15 were evaluated. Common toxicities were
      fever and leukopenia; the abnormality of laboratory tests included elevations in
      aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, C
      reactive protein, and beta2-microglobin. Dose-limiting toxicity was the grade 3
      elevation of aminotransferases, and was observed in two of six patients at the
      300-ng/kg dose level after the first course in one patient and after the third
      course in the other. Leukopenia was observed at all of the dose levels; two of
      six patients at 300 ng/kg experienced grade 3 leukopenia. Thus, 300 ng/kg was
      determined to be the maximum acceptable dose. Peak plasma levels of rhIL-12
      decreased in the second courses, but the areas under the curve were almost the
      same in the first and second courses. Biological effects included increases of
      plasma levels of IFN-gamma, tumor necrosis factor-alpha, IL-6, IL-10, and
      neopterin. In two patients with renal cell carcinoma, complete response and
      partial response of metastatic tumors were observed with 50 and 300 ng/kg; the
      responses lasted for 5 and 3.5 months, respectively. Although immunological
      response to rhIL-12 varies depending on administration route and schedule and on
      patients' physiological conditions, the recommended dose for Phase II studies is
      300 ng/kg s.c. three times a week for 2 weeks followed by 1-week rest.

PMID- 10914708
TI  - Phase II trial of paclitaxel by 96-hour continuous infusion in combination with
      cisplatin for patients with advanced non-small cell lung cancer.
AB  - Our purpose was to determine the antitumor efficacy and safety profile of the
      combination of paclitaxel administered by 96-h continuous i.v. infusion followed
      by bolus cisplatin in patients with untreated advanced non-small cell lung cancer
      (NSCLC). Fifty-eight patients with untreated advanced or recurrent NSCLC were
      enrolled between October 1995 and December 1998. The median patient age was 60
      years (age range, 34-75 years). Twenty-four patients were female. The majority of
      patients (n = 52) had an Eastern Cooperative Oncology Group performance status of
      0/1. Twelve patients had stage IIIB NSCLC, 43 had stage IV disease, and 3 had
      recurrent disease after prior resection. Seven patients had received cranial
      irradiation for brain metastases, and 5 patients had received bone irradiation
      before enrollment. Patients were treated with paclitaxel (120 mg/m2/96 h) by
      continuous i.v. infusion followed by cisplatin (80 mg/m2) on day 5. Therapy was
      administered every 3 weeks as tolerated until disease progression or a maximum of
      six cycles. A total of 264 cycles of therapy were administered. Twenty-nine
      patients received all six cycles. Forty-six patients had measurable disease, with
      20 patients achieving a partial response, and no complete responses were seen
      (overall response rate, 43%; 95% confidence interval, 29-60%). The median
      progression-free survival was 5.5 months. At a median potential follow-up of 27.2
      months, the median survival for all 58 enrolled patients was 8.5 months, and the
      actuarial 1-year survival was 37% (95% confidence interval, 25.9-50.5%). This is
      the most extensive evaluation of prolonged continuous infusional paclitaxel in
      patients with advanced-stage cancer. In contrast to predictions from in vitro
      cytotoxicity models, the regimen does not appear to be obviously superior to
      shorter infusion times in the clinical setting. Additional trials of this regimen
      in patients with NSCLC are therefore of low priority.

PMID- 10914710
TI  - Inter- and intrapatient variability in oral topotecan pharmacokinetics:
      implications for body-surface area dosage regimens.
AB  - Anticancer drugs still are dosed based on the body-surface area (BSA) of the
      individual patient, although the BSA is not the main predictor of the clearance
      for the majority of drugs. The relevance of BSA-based dosing has not been
      evaluated for topotecan yet. A retrospective pharmacological analysis was
      performed of kinetic data from four clinical Phase I studies in which topotecan
      was administered p.o. as a single agent combined with data from a combination
      study of topotecan and cisplatin. A strong correlation (r = 0.91) was found
      between the area under the plasma concentration time curve of the lactone and
      carboxylate forms of topotecan by plotting 326 data sets obtained from 112
      patients receiving oral topotecan at dose levels ranging from 0.15-2.70 mg/m2.
      The intrapatient variability, studied in 47 patients sampled for 3 or more days,
      for the apparent lactone clearance, ranged from 7.4-69% (mean, 24 +/- 13%;
      median, 20%). The interpatient variabilities in the lactone clearance, calculated
      with the data of all studied patients, expressed in liter/h/m2 and in liter/h
      were 38% and 42%, respectively. In view of the relatively high inter- and
      intrapatient variabilities in topotecan clearance, in contrast to a variability
      of only 12% in the BSA of the studied patients, no advantage of BSA-based dosing
      was found over fixed dose regimens.

PMID- 10914709
TI  - Pharmacokinetic and pharmacodynamic evaluation of the glycinamide ribonucleotide
      formyltransferase inhibitor AG2034.
AB  - Glycinamide ribonucleotide formyltransferase (GARFT) is a component of the de
      novo purine synthesis pathway. AG2034 is a specific inhibitor of GARFT that was
      designed based on the GARFT crystal structure. In conjunction with Phase I
      studies at four clinical centers in the United States and United Kingdom, AG2034
      pharmacology was evaluated in 54 patients receiving 1-11 mg/m2 AG2034 as a 2-5
      min injection. Blood samples were obtained just prior to and 5, 15, 30, and 45
      min, and 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, and 96 h after bolus injection
      during course 1. Limited sampling was also performed on course 3. Plasma AG2034
      was measured using a sensitive and reproducible ELISA assay. AG2034 demonstrated
      a trimodal elimination pattern over 24 h, with median half-life (t(1/2))alpha =
      8.7 min, t(1/2)beta = 72.6 min, and t(1/2)gamma = 364.2 min. AG2034 systemic
      clearance ranged from 9.4-144.5 ml/min/m2, and volume of distribution was 1.2-7.6
      liters/m2. Course 1 AG2034 area under the concentration versus time curve (AUC)
      had a linear relationship with dose (r(s) = 0.86). Accumulation of AG2034 was
      evident, because course 3 AUC was higher than course 1 in 23 of 23 evaluable
      patients, but was not associated with an increase in erythrocyte AG2034. AG2034
      systemic exposure had an impact on toxicity, because course 1 and course 3 AG2034
      AUCs were significantly higher for patients with grade III/IV toxicity than
      patients with less than grade II toxicity (P < 0.001 and P = 0.001 for course 1
      and course 3, respectively). This study demonstrates rapid systemic clearance of
      AG2034 and suggests pharmacokinetic approaches that may minimize patient toxicity
      and aid the development of this interesting class of anticancer agents.

PMID- 10914711
TI  - Bayesian estimate of vinorelbine pharmacokinetic parameters in elderly patients
      with advanced metastatic cancer.
AB  - The objective of the present study was to determine the pharmacokinetic profile
      of vinorelbine in patients 65 years or older with metastatic cancer in
      progression. Twelve patients were enrolled in this study. Vinorelbine was
      administered by a 10-min continuous infusion at a dose of 20-30 mg/m2 through a
      central venous catheter. Chemotherapy was repeated weekly. A total of 46 courses
      of vinorelbine was studied. Each patient underwent pharmacokinetic evaluation
      during the first cycle of treatment. Toxicity evaluation was carried out before
      each course of chemotherapy. Plasma vinorelbine determinations were performed by
      high-performance liquid chromatography with spectrofluorometric detection. A
      Bayesian estimation of individual pharmacokinetic parameters was carried out
      using the nonlinear mixed-effect modeling approach as implemented in the NONMEM
      computer program. An open three-compartment pharmacokinetic model with a zero
      order input rate was used to describe the kinetics of vinorelbine. Area under the
      plasma-concentration time curve (AUC) normalized to a 30 mg/m2 administered dose
      averaged 0.89 mg/liter x h (coefficient of variation = 23.7%). The total plasma
      clearance averaged 0.93 liter/h/kg (0.61-1.83 liter/h/kg; coefficient of
      variation = 38.6%). The elimination half-life was 38.1 +/- 5.8 h. A high
      correlation was found between patient age and total clearance (r = -0.8; P <
      0.001). The main hematological toxicity observed was anemia in 11 patients.
      Neutropenia occurred in 50% of patients. Significant correlations were found
      between AUC and the decrease in the hemoglobin level (r = 0.60) and between AUC
      and the decrease in the neutrophil count (r = 0.66). Thrombocytopenia was
      observed in only one patient. In conclusion, the age-related decrease in
      clearance found in this study supports the design of a Phase I study of
      vinorelbine in patients older than 65 years or perhaps 70 years.

PMID- 10914712
TI  - High telomerase activity is an independent prognostic indicator of poor outcome
      in colorectal cancer.
AB  - Telomerase activity and altered telomere length have been extensively studied in
      many kinds of malignant tumors for clinical diagnostic and/or prognostic
      utilities. In the present study, we investigated telomerase activity and telomere
      length in colorectal cancers and noncancerous colonic mucosa specimens in 100
      patients between 1991 and 1996. To determine whether the level of telomerase
      activity or telomere length is a prognostic indicator of patient outcome, we
      followed these patients more than 3 years after surgery. Among 100 primary
      colorectal cancer specimens, 96 specimens had telomerase activity. Because
      noncancerous mucosa has some detectable telomerase activity, we divided the
      levels of telomerase activity into three categories: high (>50-fold more than
      that in noncancerous mucosa); moderate (10- to 50-fold); and low (<10-fold)
      levels. Among 100 cancer tissues, 28 showed moderate telomerase activity and 44
      showed high telomerase activity. The frequency of tumors with moderate or high
      telomerase activity showed no significant relationship with any
      clinicopathological factors. The prognosis of the patients with high telomerase
      activity was significantly worse than that for patients with moderate and low
      telomerase activity (P < 0.01). Among the 87 patients with curative surgery,
      disease-free survival rate of those with high telomerase activity was also
      significantly poorer (P < 0.01). These results indicate that a high level of
      telomerase activity may be an independent prognosis-predicting factor in the
      patients with colorectal cancer.

PMID- 10914713
TI  - Serum interleukin 6 as a prognostic factor in patients with prostate cancer.
AB  - The present study was undertaken to evaluate the prognostic significance of the
      serum levels of interleukin 6 (IL-6) in patients with prostate cancer. Serum IL-6
      levels were measured in 74 patients with prostate cancer. The tumor was stage B
      in 23 patients, stage C in 14 patients, and stage D in 37 patients. Prognostic
      significance of tumor histology, performance status (PS), bone metastasis, serum
      prostate-specific antigen (PSA) level, serum alkaline phosphatase (ALP) level,
      serum lactate dehydrogenase level, serum IL-6 levels, and hemoglobin on disease
      specific survival was assessed using univariate and multivariate Cox's
      proportional hazards model analyses. Serum IL-6 was significantly correlated with
      the clinical stage of prostate cancer. Univariate analysis of all patients
      demonstrated that an extent of disease (EOD) on bone scanning > or = 1, IL-6 > or
      = 7 pg/ml, PS > or = 1, PSA > 100 ng/ml, and ALP > 620 IU/liter were associated
      with a significantly lower survival rate than their respective counterparts. In
      multivariate analysis, however, the only two significant prognostic factors were
      EOD and IL-6. In 51 patients with stage C and stage D prostate cancer, univariate
      analysis showed that EOD > or = 1, IL-6 > or = 7 pg/ml, PS > or = 1, PSA > 100
      ng/ml, LDH > 200 IU/liter, and ALP > 620 IU/liter were significantly related to
      survival, whereas multivariate analysis again demonstrated that EOD > or = 1 and
      IL-6 > or = 7 pg/ml were significant prognostic factors. These results indicate
      that the serum IL-6 level is a significant prognostic factor for prostate cancer
      as well as EOD.

PMID- 10914714
TI  - Thymidylate synthase expression correlates closely with E2F1 expression in colon
      cancer.
AB  - Thymidylate synthase (TS) is thought to be one of the target genes that the E2F1
      transcription factor binds to and regulates. However, the relationship between
      the expressions of TS and E2F1 in primary colon cancer specimens remains unclear.
      The aim of this study was to define the relation of TS and E2F1 gene expressions
      in tumor samples from 23 colon cancer patients. TS and E2F1 gene expressions were
      measured by TaqMan reverse transcription-PCR assay using glyceraldehyde-3
      phosphate dehydrogenase (GAPDH) as an internal standard and expressed as a
      TS:GAPDH or E2F1:GAPDH mRNA ratio. A close relationship was found between TS gene
      expression and E2F1 gene expression (r2 = 0.598, P < 0.001) in 23 tumor samples
      analyzed. Surprisingly, a high correlation between TS gene expression and E2F1
      gene expression was observed even in advanced tumors from stage IV colon cancer
      patients. These results suggest that transcription of the TS gene may be
      regulated by E2F1 in primary colon cancer specimens and that this gene-regulatory
      pathway from E2F1 to TS may be highly conserved during malignant progression.
      Four of the 23 patients showed TS overexpression with increased E2F1 expression.
      These results suggest that the ability of a tumor to increase TS expression may
      possibly be due to an overexpression of E2F1. Although the number of patients was
      relatively small, our study provides new insights into the molecular mechanisms
      underlying the regulation of TS expression in colon cancers.

PMID- 10914715
TI  - Differences in 20q13.2 copy number between colorectal cancers with and without
      liver metastasis.
AB  - Frequent gains of 20q have been identified recently in many neoplasias, including
      breast, bladder, ovarian, pancreatic, and colon cancers. A high level of 20q13.2
      amplification is associated with poor prognosis in breast cancer. We investigated
      the copy number of the 20q13.2 region including the ZNF217 oncogene in 17
      nonmetastatic colorectal cancers (CRCs), 18 primary CRC tumors with liver
      metastasis, and 18 metastatic lesions by two-color fluorescence in situ
      hybridization to evaluate the significance of an increased copy number of 20q13.2
      in CRC, especially in those cases with liver metastasis. The frequency of
      increased relative copy number of the 20q13.2 region was higher in primary and
      liver metastatic lesions of CRC than in CRC lesions without liver metastasis. In
      particular, a high-level increase (>3.0-fold) in the relative copy number of
      20q13.2 was observed in 2 of 18 (11%) primary CRC lesions with liver metastasis,
      7 of 18 (39%) liver metastatic lesions, and in none of the cases of primary CRC
      without liver metastasis. The absolute and relative copy number of chromosome
      20q13.2 was higher in CRCs with metastasis than in CRCs without metastasis. The
      percentage of cells with high-level 20q13.2 amplification was also higher in both
      lesions with metastasis per specimen than without metastasis. Our results suggest
      that the level of 20q13.2 amplification correlates with the metastatic potential
      and tumor progression of CRC. The results also suggest that 20q13.2 amplification
      with ZNF217 is associated with increased metastatic potential.

PMID- 10914716
TI  - Detection of minimal residual cancer to investigate why oral tumors recur despite
      seemingly adequate treatment.
AB  - Improvements in surgery and radiotherapy techniques have led to only a modest
      increase in the 5-year survival rate for patients with head and neck cancer. This
      is because the pattern of clinical disease is changing, such that locoregional
      recurrence now accounts for fewer treatment failures, but more patients develop a
      second primary cancer or distant metastatic disease. In this study, we have used
      the p53 phage plaque assay, immunocytochemistry, and mutational analysis to
      assess the contribution of minimal residual cancer and genetic aberrations in
      clinically normal upper aerodigestive tract mucosa to treatment failure. Eighteen
      consecutive patients with oral tumors, with conventional clear margins, have been
      followed for a minimum of 36 months. Molecular assessment identified tumor
      positive surgical margins for 6 of 11 assessable patients and additional tumor
      positive lymph nodes for three cases. Disseminated malignant cells were detected
      in the hematopoietic cell compartment for six cases, and one patient had
      molecular evidence of field cancerization. Locoregional recurrence developed in
      five patients with tumors harboring a p53 gene mutation; four of these were
      associated with tumor-positive surgical margins, and one was associated with
      molecular evidence of field cancerization. Radiotherapy to the primary site did
      not prevent development of local recurrence when the residual tumor harbored a
      p53 gene mutation. Three of six cases with a tumor-positive bone marrow aspirate
      developed distant metastases. These findings reveal that molecular and
      immunocytochemical detection of minimal residual cancer and field cancerization
      can help identify patients who may develop locoregional or distant recurrence and
      justify further studies to evaluate the contribution of these remaining malignant
      cells to treatment failure.

PMID- 10914717
TI  - Differential expression of matrix metalloproteinase (MMP)-2, MMP-9, and membrane
      type 1-MMP in hepatocellular and pancreatic adenocarcinoma: implications for
      tumor progression and clinical prognosis.
AB  - In the present study, we used in situ hybridization to study 36 primary
      hepatocellular carcinomas (HCCs) and 35 pancreatic adenocarcinomas to analyze the
      expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP), MMP-2, and MMP
      9 mRNAs. In HCCs, MT1-MMP mRNA was mainly expressed by cancer cells and to a
      lesser extent by stromal cells. MMP-2 mRNA was expressed predominantly by cells
      of tumor stroma, whereas MMP-9 mRNA was seen mainly in neoplastic epithelial
      cells. In pancreatic adenocarcinomas, MT1-MMP and MMP-9 mRNA were seen at
      moderate levels both in cancer and in stromal cells, whereas MMP-2 mRNA was
      predominantly expressed by the tumor stroma. Antigens of MMP-2, MMP-9, and MT1
      MMP immunolocalized to the neoplastic epithelium and to the stromal cells in both
      tumor types. In gelatin zymography, increased amounts of latent and active MMP-2
      were found in tumor samples of HCC as compared with adjacent nontumorous liver
      tissue. On the other hand, the latent form of MMP-9 was found in almost equal
      amounts both in tumor and normal liver samples, but its active form was present
      only in HCC. Expression of MT1-MMP mRNA had a tendency to be associated with a
      lower degree of differentiation in HCC, but such association was not noticed in
      pancreatic tumors. Correlation to the clinical data showed that MT1-MMP
      expression had a strong statistical association with a poor outcome of patients
      (P < 0.01). A similar tendency was also observed in pancreatic adenocarcinomas,
      but the association did not reach statistical significance. MMP-2 and MMP-9 mRNA
      expression did not have significant correlation with prognosis. The results of
      this study support the previous suggestions of the importance of MT1-MMP for
      malignant growth and indicate that increased MT1-MMP mRNA expression by tumor
      cells in HCCs and pancreatic adenocarcinomas may have prognostic significance.

PMID- 10914718
TI  - Regulation of disease-progression genes in human gastric carcinoma cells by
      interleukin 8.
AB  - The expression of interleukin 8 (IL-8) by human gastric carcinomas directly
      correlates with tumor vascularity and disease progression. To determine whether
      IL-8 can act in an autocrine manner to regulate the expression of other disease
      progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1)
      and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38
      surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell
      lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical
      specimens, the majority of the tumor cells and small vessel endothelial cells
      stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human
      gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of
      epidermal growth factor receptor, type IV collagenase (metalloproteinase-9),
      vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with
      exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased
      invasive capacity of MKN-1 cells, which was associated with activity of
      metalloproteinase-9. Collectively, these results demonstrate that human gastric
      carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the
      progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.

PMID- 10914719
TI  - Analytical variables of reverse transcription-polymerase chain reaction-based
      detection of disseminated prostate cancer cells.
AB  - Early systemic spread of occult tumor cells that may develop into founders of
      incurable distant metastasis has been identified in prostate cancer patients by
      reverse transcription-PCR (RT-PCR) amplification of prostate-specific antigen
      (PSA) mRNA. Nevertheless, the introduction of this new staging tool into the
      clinical setting has been hampered by the disparate and contradictory data on the
      sensitivity and specificity of RT-PCR methods reported recently. We used PSA RT
      PCR to examine the influence of analytical variables such as priming and enzyme
      of reverse transcriptase reaction, temperature and time of primer annealing,
      primer extension and denaturation, as well as the concentrations of magnesium
      chloride, Taq polymerase, deoxynucleotide triphosphate, primers and BSA on the
      amplification process. By systematically varying these chemical and physical
      components, we could demonstrate a significant increase in amplification yield
      and in stringency of primer annealing. This may explain the wide variety of
      published findings on molecular staging of prostate cancer, which currently
      impedes the clinical introduction of PSA RT-PCR assays in prostate cancer.
      Methodological analyses are needed for standardization and quality assurance to
      achieve reproducible molecular methods that can be used in clinical practice.

PMID- 10914720
TI  - p53 but not bcl-2 immunostaining is predictive of poor clinical complete response
      to primary chemotherapy in breast cancer patients.
AB  - Preoperative chemotherapy administered to breast cancer (BC) patients is a model
      for studying in vivo the interaction between cytotoxic treatment and clinical and
      biological parameters. Apoptosis induced by anticancer agents is a mechanism of
      treatment activity; therefore, overexpression of genes inhibiting the apoptotic
      pathway could produce drug resistant tumors. In the present study, the two most
      studied inhibitors of apoptosis, the bcl-2 gene and the mutant p53, have been
      evaluated to assess whether they may play a role in modulating response of BC to
      primary chemotherapy. From August 1990 to January 1997, 143 patients bearing T(2
      4)N(0-1)M0 primary BC were submitted to two different chemotherapeutic regimens
      before surgery. The first 64 received the cyclophosphamide, methotrexate, 5
      fluorouracil (CMF) regimen (on days 1 and 8 and every 28 days thereafter)
      associated with tamoxifen (30 mg daily) in case of estrogen receptor (ER)
      positive BC, and the remaining 79 were submitted to single agent epirubicin (120
      mg/m2 every 21 days). The expression of p53, bcl-2, Ki67, ER, progesterone
      receptor, c-erbB2, and the multidrug resistance P-glycoprotein (gp-170) was
      evaluated in BC specimens obtained at diagnosis by incision biopsy and at
      postchemotherapy surgery. At the end of chemotherapy administration (median, 3
      cycles; range, 2-6), the clinical complete response (cCR) rate was superimposable
      in the patient subgroups with bcl-2-positive or -negative primary tumors;
      conversely, p53 expression, at a cutoff of 10% positive cells, was significantly
      associated with a lower cCR rate (9.4 versus 27.0%; P < 0.04). p53 was a
      significant predictor for poor cCR in the subset submitted to epirubicin (3.6
      versus 25.5%; P < 0.02; in patients with p53+ and p53- BC, respectively); by
      contrast, only a trend toward lower cCR has been observed in patients with p53+
      tumors receiving CMF +/- tamoxifen with respect to p53- ones. The distribution of
      cCR according to the gp-170-positive or -negative tumors was 8 versus 22% in
      patients submitted to epirubicin and 29 versus 30% in those receiving CMF +/-
      tamoxifen, respectively. In a multivariate regression analysis, after adjusting
      for treatment administered (epirubicin versus CMF +/- tamoxifen), menopausal
      status, tumor and node status, histology grade, ER, progesterone receptor, c
      erbB2, Ki67, bcl-2, and gp-170 expression, the p53 status maintained an
      independent predictive role for cCR. Most of the tumors undergoing change in
      percentage of p53 expression after both treatments originally harbored mutant
      protein, and only four BC specimens that were p53 negative before chemotherapy
      became positive afterward. These data confirm in vivo the concept that the
      responsiveness of tumors to chemotherapy in part derives from the capability of
      BC cells to undergo apoptosis. The role of mutated p53 in preventing response is
      more evident in patients submitted to epirubicin, and this may be caused by the
      up-regulation of multidrug resistance gene expression by p53 inactivation. p53 is
      a stable phenotype and is not inducible by at least three or four chemotherapy
      cycles.

PMID- 10914721
TI  - Mutations of the INI1 rhabdoid tumor suppressor gene in medulloblastomas and
      primitive neuroectodermal tumors of the central nervous system.
AB  - Germ-line and somatic mutations of the hSNF5/INI1 gene have been reported in
      atypical teratoid/rhabdoid tumors (AT/RTs) of the brain, consistent with its role
      as a tumor suppressor gene. In the present study, we determined the frequency of
      deletions and mutations of INI1 in 52 children whose original diagnosis was
      medulloblastoma (MB) or primitive neuroectodermal tumor (PNET) of the central
      nervous system. Mutations were detected in DNA isolated from four tumors, all
      from children less than 3 years of age at diagnosis. Two of the four were
      reviewed and reclassified as atypical teratoid tumor, whereas there was
      insufficient material to establish this diagnosis in the two remaining cases. The
      relatively low frequency of mutations, even in a large series of infants,
      suggests that loss of sequences from chromosome 22 and/or mutations of INI1 do
      not account for the poor prognosis of children with MB or PNET who are less than
      3 years of age at diagnosis. Nevertheless, chromosome 22 deletion and INI1
      mutation analysis of infants with MB/PNET should be considered for all children
      who are less than 1 year of age. Detection of these mutations suggests that the
      child has an AT/RT, rather than a MB/PNET, a finding with important prognostic
      value.

PMID- 10914722
TI  - Expression of gonadotropin and activin receptor messenger ribonucleic acid in
      human ovarian epithelial neoplasms.
AB  - Activin receptors (ActRs) and gonadotropin receptor mRNA expression were
      investigated in 18 human ovarian epithelial neoplasms. Northern blot analysis
      showed the presence of 3.0-kb type Ia ActR, 6.0- and 3.0-kb type IIa ActR, and
      5.0-kb type IIb ActR mRNA transcripts in total RNA prepared from the cancer
      tissues. One carcinoma showed two major transcripts of a follicle-stimulating
      hormone receptor (FSH-R) gene, 4.1 and 2.4 kb, whereas the other two carcinomas
      showed two major transcripts of the luteinizing hormone/human chorionic
      gonadotropin receptor (LH-R) gene, 5.4 and 2.4 kb. These results were further
      analyzed by studying the corresponding PCR-amplified FSH and LH-R cDNA obtained
      by reverse transcription of total RNA. Expression of FSH-R mRNA was confirmed in
      about half of the cancer tissues. The size of the FSH-R reverse transcription-PCR
      product was the same as in normal ovarian follicles. Similarly, expression of LH
      R mRNA was also detected in about half of the cancers. Normal ovaries and cancer
      tissues were homogenized, and activin concentrations were measured in extracts.
      Activin levels in normal ovarian tissue were around 0.59 +/- 0.01 ng/mg protein
      (mean +/- SE; n = 5), and activin production was detected in every cancer tissue,
      except one--serous adenocarcinoma. The findings in this study demonstrated that
      activin and ActRs are present in and synthesized by human ovarian epithelial
      neoplasms. Thus, activin seems to be available as an autocrine/paracrine factor
      in epithelial neoplasms and may contribute to the expression of FSH-R, although
      the roles of activin and gonadotropin in tumorigenesis has yet to be defined.

PMID- 10914723
TI  - Comparison of telomerase activity in bladder carcinoma and exfoliated cells
      collected in urine and bladder washings, using a quantitative assay.
AB  - Telomerase activity was measured with a quantitative assay, based on a
      modification of telomeric repeat amplification protocol method, in bladder
      cancers and apparently normal mucosa in 33 patients. In the same patients, the
      enzyme was also measured in exfoliated cells collected both with voided urine and
      bladder washings. Results obtained in urine were compared with those from 20
      healthy subjects. Telomerase activity was present in 31 (94%) bladder cancer
      tissues and in 23 (72%) apparently normal mucosa samples. However, the levels of
      enzyme activity were significantly higher in cancer tissues in comparison with
      normal mucosa (mean +/- SD, 47.3 +/- 23.2 and 14.9 +/- 6.1 ng DNA/microg protein,
      respectively; P < 0.0001). Telomerase activity in bladder cancer tissues was not
      related to tumor stage and grade. Enzyme activity was present in 27 urine samples
      and in 27 (82%) bladder washings collected from cancer patients. We did not find
      correlation between the activity in urine and washings, and their mean levels
      were not different (22.2 +/- 10.1 and 20.7 +/- 8.0, respectively). Telomerase
      activity in bladder cancer tissues was correlated to its activity in urine (r =
      0.650, P < 0.001) and in bladder washings (r = 0.410, P < 0.05). Only 2 of 20
      urine samples from control subjects were found to express telomerase activity at
      a very low level. This was the first attempt to correlate telomerase activity in
      exfoliated cells from urine and bladder washings with the activity in
      corresponding bladder cancers. According to these results we postulate that
      telomerase activity in urine sediment reflects the activity in bladder cancers
      better than bladder washings and, for its easy collection, is to be preferred as
      diagnostic marker in this tumor.

PMID- 10914724
TI  - INK4a gene expression and methylation in primary breast cancer: overexpression of
      p16INK4a messenger RNA is a marker of poor prognosis.
AB  - Frequent deletions or mutations of the INK4 gene, which encodes the cyclin
      dependent kinase 4 inhibitor p16INK4a, have been documented in various human
      cancers, but little is known about the role of this tumor suppressor gene in
      primary breast cancer. We examined p16INK4a mRNA expression and its relationship
      with cyclin D1 and estrogen receptor (ER) expression in 314 primary breast
      cancers using Northern blots probed with a p16 exon 1alpha-specific cDNA. Tumor
      samples overexpressing p16INK4a were predominantly ER negative with low levels of
      cyclin D1. Cyclin D1 and ER mRNA levels in the high p16INK4a expressers were
      significantly lower than those in the remainder of the population (P = 0.0001).
      Furthermore, the mean p16INK4a mRNA level in the ER-negative tumors was
      significantly higher than that in the ER-positive group (P = 0.0001). Because the
      INK4 gene is frequently inactivated by de novo methylation, we investigated the
      frequency of INK4a exon 1alpha methylation in a subset of 120 primary breast
      cancers using methylation-specific PCR; 24 of these were methylated. These
      findings indicate that high expression of p16INK4a and reduced expression due to
      de novo INK4a methylation are frequent events in primary breast cancer. In a
      subset of 217 patients for whom detailed clinical data were available, high
      p16INK4a mRNA expression was associated with high tumor grade (P = 0.006), > or =
      4 axillary lymph node involvement (P = 0.004), ER negativity (P = 0.0001), and
      increased risk of relapse (P = 0.006). The significant negative correlation
      between p16INK4a and ER gene expression raises issues regarding their functional
      interrelationships and whether high p16INK4a expression may be associated with a
      lack of hormone responsiveness in breast cancer.

PMID- 10914725
TI  - Monoclonality of multifocal myxoid liposarcoma: confirmation by analysis of TLS
      CHOP or EWS-CHOP rearrangements.
AB  - Multifocal presentation, defined as the presence of tumor at two or more
      anatomically separate sites, before the manifestation of disease in sites where
      sarcomas usually metastasize (e.g., lungs) occurs in about 1% of extremity soft
      tissue sarcomas (STSs). Debate still persists whether multifocal STSs represent
      an unusual pattern of metastasis or multiple separate primary tumors. Among STSs
      with multifocal presentation, myxoid liposarcoma is the predominant histological
      type. This subtype of liposarcoma contains the specific t(12;16) chromosomal
      translocation, which results in rearrangement of the TLS and CHOP genes that is
      clone specific at the DNA level. We, therefore, sought to address the question of
      clonality by molecular analysis in six patients who presented with either
      synchronous or metachronous multifocal myxoid liposarcoma. In all six cases,
      adequate frozen tumor was available for DNA extraction from at least two distinct
      anatomical sites. Southern blot analysis using CHOP, TLS, and EWS cDNA probes was
      performed on genomic DNA. Five cases contained a TLS-CHOP rearrangement, and one
      case had the variant EWS-CHOP fusion (seen in <5% of cases). The size of the
      rearranged CHOP fragment differed among the six patients, as expected, but was
      identical in all anatomically separate tumor samples from each patient. Likewise,
      the sizes of the rearranged bands observed with either the TLS or EWS probes
      supported the monoclonality of all cases. Our results confirm the monoclonal
      origin of multifocal myxoid liposarcoma, establishing the metastatic nature of
      distant soft tissue lesions in these cases. It remains unclear whether this
      unusual pattern of metastasis represents an intrinsic property of this subset of
      myxoid liposarcoma or merely a rare chance occurrence. The clinical outcomes
      observed in this small series suggest that the prognosis of multifocal myxoid
      liposarcoma is poor, regardless of its often bland or "low-grade" histological
      appearance.

PMID- 10914726
TI  - Human leukocyte antigen class I allelic and haplotype loss in squamous cell
      carcinoma of the head and neck: clinical and immunogenetic consequences.
AB  - The expression of human leukocyte antigen (HLA) class I molecules on the cell
      surface is necessary for the presentation of peptide antigens to cytotoxic CD8+ T
      lymphocytes of the immune system. Down-regulation of HLA class I gene expression
      has been implicated in tumorigenesis, including squamous cell carcinoma of the
      head and neck (SCCHN). Loss of MHC class I antigens may be one mechanism by which
      tumor cells escape immune detection. We performed prospective immunostaining of
      26 primary SCCHN tumors and samples of normal mucosa harvested several
      centimeters away from the primary tumor, using a large panel of antibodies
      directed against allele-specific as well as monomorphic determinants of HLA class
      I molecules. Loss of expression of HLA class I proteins in the tumor was found in
      50% (13 of 26) of primary tumors and was highly correlated with HLA loss in the
      corresponding normal mucosa (P < 0.0001). Further analysis demonstrated that the
      loss of HLA class I expression in the tumor was significantly associated with
      regional lymph node metastases (nodal stage; P = 0.0388), and that the number of
      HLA class I alleles lost in the normal mucosa was associated with subsequent
      development of a new primary aerodigestive tract cancer (P = 0.042). A patient
      with two metachronous cancers available for analysis had no evidence of HLA loss
      in the first tumor, demonstrated allelic loss in the second cancer, and
      subsequently died of disease. These results suggest that the loss of expression
      of HLA class I alleles may have prognostic implications.

PMID- 10914727
TI  - Expression of vascular endothelial growth factor can predict event-free survival
      in stage II colon cancer.
AB  - The usefulness of chemotherapy in patients with stage II disease continues to be
      debated. Biological prognostic factors may allow further insight into the optimal
      treatment strategy for patients with node-negative disease. Vascular endothelial
      growth factor (VEGF) seems to be essential for angiogenesis and for the growth of
      colorectal cancer. Recently, it was shown able to predict disease recurrence in
      patients with stage II colon cancer. Specimens of surgically resected colon
      cancer were immunostained for VEGF. Consecutive patients referred to the study
      institutions were considered eligible for this study. The main inclusion criteria
      were stage II tumor, sufficient tumor material, and adequate follow-up
      information. Analysis was performed on 121 patients. The recurrence rate in the
      patients with VEGF-positive tumors was 50% (18 of 36 patients), which was
      significantly higher than that observed in patients with VEGF-negative tumors
      [11.7% (10 of 85 patients); P = 0.001]. Also the degree of VEGF immunoreactivity
      was significantly higher in 28 relapsing patients compared with 93 disease-free
      patients (mean VEGF score, 2.84 0.38 versus 0.66 +/- 0.17; P = 0.0001). VEGF may
      be used in a clinical setting to identify patients at high risk for relapse who
      may benefit from adjuvant treatment including new therapeutic strategies such as
      monoclonal antibody neutralizing VEGF.

PMID- 10914728
TI  - Expression of the hypoxically regulated angiogenic factor adrenomedullin
      correlates with uterine leiomyoma vascular density.
AB  - Uterine leiomyomas are the most prevalent benign tumor type in women of
      reproductive age and are one of the most common indications for hysterectomy. The
      expression of five angiogenic factors, adrenomedullin (ADM), vascular endothelial
      growth factor (VEGF), acidic fibroblast growth factor, basic fibroblast growth
      factor, and platelet-derived endothelial cell growth factor/thymidine
      phosphorylase, were examined in 91 uteri collected throughout the menstrual
      cycle; 52 of which contained leiomyomata, and the remainder were normal controls.
      The microvascular density and endothelial proliferative indices were then
      determined for each of the uterine sections. ADM and VEGF were the most widely
      expressed angiogenic factors in the leiomyomas. Furthermore, the expression of
      ADM and VEGF in the endometrium and myometrium was up-regulated in leiomyoma
      bearing uteri compared with controls. Although acidic fibroblast growth factor
      and basic fibroblast growth factor were expressed in leiomyomas and endometrium
      in all of the uterine samples examined, they were only expressed in the
      myometrium of leiomyomata-bearing uteri. Endothelial proliferation in leiomyomas
      was statistically greater than that of the myometrium and endometrium, both
      within and between uteri (P < 0.05). The vascular density in the myometrium but
      not the endometrium was significantly increased in leiomyoma-containing uteri (P
      < 0.05). Expression of ADM alone correlated directly with vascular density and
      endothelial cell proliferation index in leiomyomas and myometrium and may account
      for the high vascularity found in leiomyomas and the myometrium of leiomyoma
      bearing uteri. As such, ADM is identified as a novel target for antiangiogenic
      therapy of these benign, clinically problematic uterine tumors.

PMID- 10914729
TI  - Relationship between chromosomal instability and intratumoral regional DNA ploidy
      heterogeneity in primary gastric cancers.
AB  - The purpose of this study was to elucidate the relationship between intratumoral
      regional heterogeneity in DNA ploidy and chromosomal instability (CIN) in primary
      gastric adenocarcinomas. In 45 sporadic gastric adenocarcinomas, we measured DNA
      ploidy and numerical aberrations for chromosomes 7, 11, 17, and 18 by laser
      scanning cytometry and fluorescence in situ hybridization, respectively, in small
      tissue specimens taken from 2 to 6 (on the average 4) different portions of the
      same tumor. A total of 231 specimens including 45 normal control specimens were
      examined. All 98 tumor specimens with DNA aneuploidy (DNA index > or = 1.2)
      showed large intercellular variations in chromosome copy number, indicating CIN.
      In contrast, 85 tumor specimens with (near) diploidy (1.0 < or = DNA index < 1.2)
      exhibited much small intercellular variations in chromosome copy number as
      compared with aneuploid specimens (P < 0.0001). The relationship between DNA
      ploidy and intercellular variation in chromosome copy number was true for tumors
      consisting of a mixture of (near) diploid and aneuploid subpopulations. These
      data indicate that DNA aneuploidy is associated with CIN but that (near) diploidy
      is not. Intratumoral regional DNA ploidy heterogeneity was conspicuous in 33
      (92%) of 36 tumors with regions of DNA aneuploidy, and all aneuploid specimens
      showed great intercellular variation in chromosome copy number. Diploid regions
      were predominant in early stage cancers (intramucosal and submucosal cancers),
      and five of eight early cancers contained only diploid population. In contrast,
      all tumors without (near) diploid regions were advanced cancers. These
      observations suggest that CIN is a necessary prerequisite for developing
      intratumoral DNA ploidy heterogeneity with DNA aneuploidy.

PMID- 10914730
TI  - Expression of vascular endothelial growth factor and microvessel density in head
      and neck tumorigenesis.
AB  - Angiogenesis is a fundamental process in tumor growth and metastasis, and its
      significance and that of vascular endothelial growth factor (VEGF) expression as
      prognostic indicators have been documented for various types of human tumors.
      However, the mechanisms responsible for angiogenesis in head and neck squamous
      cell carcinoma are not well defined. To examine the relationship between
      angiogenesis and the phenotypic progressions of head and neck tumorigenesis, we
      used immunohistochemistry to analyze VEGF expression and microvessel density in
      70 paraffin-embedded specimens that contained adjacent normal epithelium,
      premalignant lesions, or both from 57 patients with head and neck squamous cell
      carcinoma. Ten samples of normal oral mucosa were obtained from people who did
      not smoke or drink alcohol and included in the analysis as normal controls.
      Microvessel density was evaluated by averaging 10 microscopic fields (x400) in a
      defined area of each specimen. The degree of VEGF expression was assessed on a
      cell-by-cell basis in 10 microscopic fields (x200) in a defined area on a scale
      ranging from 0 (no expression) to 3+ (highest level of expression). In addition,
      the weighted mean index of VEGF expression was calculated. The mean +/- SD
      weighted mean index of VEGF expression in normal control epithelium (1.10 +/-
      0.38, n = 10) was higher than it was in adjacent normal epithelium (0.82 +/-
      0.27, n = 13; P = 0.04). VEGF expression decreased as samples ranged from normal
      adjacent epithelium to hyperplasia (0.78 +/- 0.28, n = 21), mild dysplasia (0.70
      +/- 0.29, n = 28), moderate dysplasia (0.67 +/- 0.29, n = 11), severe dysplasia
      (0.51 +/- 0.39, n = 6), and squamous cell carcinoma (0.20 +/- 0.27, n = 70;
      overall P = 0.0001). VEGF expression was two times lower in cases with nodal
      disease (0.17 +/- 0.26, n = 29) than it was in nonnodal disease (0.32 +/- 0.29, n
      = 16; P = 0.02). Microvessel density showed no significant difference from
      adjacent normal epithelium premalignant lesions to cancer. In tumor, no
      correlation was seen between VEGF expression or microvessel density and
      differentiation, primary tumor site, T stage, or smoking status. These findings
      indicate that VEGF expression is down-regulated during head and neck
      tumorigenesis. However, further studies are required to better understand the
      mechanism of VEGF down-regulation in head and neck tumorigenesis.

PMID- 10914731
TI  - Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic
      acid)-conjugated paclitaxel and its antitumor efficacy.
AB  - The poly(L-glutamic acid)-paclitaxel (PG-TXL) conjugate has been shown to exhibit
      significantly greater antitumor activity than conventionally formulated
      paclitaxel (TXL) against solid tumors (Li et al., Cancer Res., 58: 2404-2409,
      1998). Here we report that local tumor irradiation enhanced the distribution of
      PG-TXL given 24 h later to ovarian OCa-1 carcinoma implanted i.m. in C3Hf/Kam
      mice. Radiation significantly increased tumor uptake of PG-TXL and tumor vascular
      permeability, caused elevation of the serum concentration of vascular endothelial
      growth factor, and arrested OCa-1 cells in the G1 phase of cell cycle. The
      enhancement factors, as measured by incremental tumor growth delay compared with
      PG-TXL alone, ranged from 1.36-4.44. Complete tumor regression was also observed
      at a higher radiation dose (>10 Gy) and a higher PG-TXL dose (>80 mg
      equivalentTXL/kg). Furthermore, combined radiation and PG-TXL produced a
      significantly greater tumor growth delay than treatment with radiation and TXL
      when both drugs were given at the same equivalent TXL dose of 60 mg/kg 24 h after
      tumor irradiation (enhancement factors, 4.44 versus 1.50). These data suggest
      that conjugation of TXL to poly(L-glutamic acid) is necessary for improved
      response and that the supra-additive effect of combined radiation and PG-TXL
      therapy is due in part to modulation of the enhanced permeability and retention
      effect of macromolecules by radiation. We propose a treatment strategy combining
      radiation and macromolecular chemotherapy that may have important clinical
      implications in terms of scheduling and optimization of the therapeutic ratio.

PMID- 10914732
TI  - Immunotoxins with increased activity against epidermal growth factor receptor
      vIII-expressing cells produced by antibody phage display.
AB  - Recombinant immunotoxins are fusion proteins composed of Fv regions of antibodies
      and bacterial or plant toxins that are being developed for the targeted therapy
      of cancer. MR1(Fv)-PE38 is a single-chain recombinant immunotoxin that targets a
      mutant form of the epidermal growth factor receptor (EGFR), EGFRvIII, that is
      frequently overexpressed in malignant glioblastomas. We have used random
      complementarity determining region (CDR) mutagenesis to obtain mutants of MR1(Fv)
      with an increased affinity for EGFRvIII and an increased activity when converted
      to a recombinant immunotoxin. Initially, nine residues of heavy chain CDR3 were
      randomly mutagenized, and several mutants with increased binding affinity were
      isolated. All mutations were located at amino acids 98 and 99, which correspond
      to a DNA hot spot, a DNA sequence that mutates at high frequency during natural
      antibody maturation. A specific region of variable region of antibody light chain
      CDR3 was mutagenized that corresponded to a hot spot and a mutant (MR1-1) with an
      additional increase in affinity, and cytotoxic activity was isolated. These
      studies show that targeting hot spots in the CDRs of Fvs is an effective approach
      to obtaining Fvs with increased affinity. The increased affinity of MR1-1(Fv)
      makes it an attractive candidate for the targeted therapy of glioblastomas.

PMID- 10914733
TI  - Delayed micromolar elevation in intracellular calcium precedes induction of
      apoptosis in thapsigargin-treated breast cancer cells.
AB  - Thapsigargin (TG), a highly specific inhibitor of the sarcoplasmic reticulum and
      endoplasmic reticulum Ca2+-ATPase pump, can induce apoptosis in a variety of
      epithelial and lymphoid cell types. In prostate cancer cell lines, TG induces an
      initial 5- to 10-fold elevation of intracellular calcium ([Ca2+]i) within a few
      minutes of exposure. With prolonged exposure times (i.e., 12-36 h) a second
      elevation of [Ca2+]i to >10 microM is observed. In this study, the human breast
      carcinoma cell lines MCF-7 and MDA MB 468 cells were used to determine the
      temporal relationship between TG-induced elevation of [Ca2+]i and activation of
      programmed cell death. Using a microinjection method that allows for long-term
      analysis of [Ca2+]i changes, we found that after TG exposure, calcium
      measurements in these cells demonstrated an initial rise (>4-fold) in [Ca2+]i
      that occurred within minutes and returned to baseline within a few hours. With
      prolonged TG exposure, the cells underwent a second elevation (>5 microM) of
      [Ca2+]i occurring stochastically between 12 and 36 h after the initial exposure
      to TG. Both of the cell lines were growth-inhibited by 100 nM TG after only 1 h
      of exposure, but clonogenic ability in the MCF-7 cells was significantly reduced
      only after 48 h of exposure. The induction of apoptosis by TG was demonstrated by
      morphological changes typical for programmed cell death and DNA fragmentation
      (both high molecular weight and oligonucleosomal-sized fragments were detected)
      after 48 h of treatment. TG induction of apoptosis in these breast cancer cells
      occurred subsequent to the secondary rise in [Ca2+]i, which confirmed that this
      secondary rise in [Ca2+]i is not prostate cancer-specific. The secondary rise in
      [Ca2+]i to micromolar levels may directly activate the endonucleases responsible
      for DNA fragmentation that occurs as part of the apoptotic process. These studies
      indicate that TG is an active agent in vitro against breast cancer cells.
      Inactive prodrug analogues of TG are currently being developed that can be
      activated by tissue-specific proteases, and further pursuit of this strategy as a
      potential treatment for breast cancer is warranted.

PMID- 10914734
TI  - Induction of apoptosis in human esophageal cancer cells by sequential transfer of
      the wild-type p53 and E2F-1 genes: involvement of p53 accumulation via ARF
      mediated MDM2 down-regulation.
AB  - Transcriptional factor E2F-1 as well as tumor suppressor p53 have been shown to
      cause apoptosis independently in some types of human cancer cells when
      overexpressed. Here we report that sequential transfer of the wild-type p53 and
      E2F-1 genes efficiently induces apoptosis in human esophageal cancer cells and
      that E2F-1 overexpression directly, activates expression of p14 (ARF), which
      inhibits MDM2-mediated p53 degradation, resulting in the stabilization of p53.
      Infection of human esophageal cancer cell lines T.Tn and TE8 with adenovirus
      vector-expressing E2F-1 (Ad-E2F-1) enhanced mRNA and protein expression of ARF
      and decreased MDM2 protein expression. Transfection of ARF plasmid decreased MDM2
      protein expression, which in turn increased p53 protein expression. Infection of
      T.Tn and TE8 cells first with adenovirus-expressing wild-type p53 (Ad-p53) and
      then with Ad-E2F-1 resulted in rapid induction of apoptosis; in contrast,
      simultaneous infection with Ad-E2F-1 and Ad-p53 had no significant antitumor
      effect. As shown by Western blot analysis, infection with suboptimal
      concentrations of Ad-E2F-1 induced the accumulation of exogenous p53 transduced
      by suboptimal concentrations of Ad-p53. Moreover, Ad-E2F-1-mediated ARF
      expression inhibited the up-regulation of MDM2 by overexpressed p53 in TE8 cells.
      Thus, overexpression of ectopic E2F-1 protein may stabilize endogenous as well as
      ectopic p53 protein via the E2F-1/ARF/MDM2/p53 regulatory pathway and, in this
      way, render cells more sensitive to apoptosis, an outcome that has important
      implications for the treatment of human esophageal cancers.

PMID- 10914735
TI  - Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by
      novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human
      tumor cell lines.
AB  - Potent poly(ADP-ribose) polymerase (PARP) inhibitors have been developed that
      potentiate the cytotoxicity of ionizing radiation and anticancer drugs. The
      biological effects of two novel PARP inhibitors, NU1025 (8-hydroxy-2
      methylquinazolin-4-[3H]one, Ki = 48 nM) and NU1085 [2-(4
      hydroxyphenyl)benzamidazole-4-carboxamide, Ki = 6 nM], in combination with
      temozolomide (TM) or topotecan (TP) have been studied in 12 human tumor cell
      lines (lung, colon, ovary, and breast cancer). Cells were treated with increasing
      concentrations of TM or TP +/- NU1025 (50, 200 microM) or NU1085 (10 microM) for
      72 h. The potentiation of growth inhibition by NU1025 and NU1085 varied between
      the cell lines from 1.5- to 4-fold for TM and 1- to 5-fold for TP and was
      unaffected by p53 status. Clonogenic assays undertaken in two of the cell lines
      confirmed that the potentiation of growth inhibition reflected the potentiation
      of cytotoxicity. NU1025 (50 microM) was about as effective as 10 microM NU1085 at
      potentiating growth inhibition and cytotoxicity, consistent with the relative
      potencies of the two molecules as PARP inhibitors. Potentiation of cytotoxicity
      was obtained at concentrations of NU1025 and NU1085 that were not toxic per se;
      however, NU1085 alone was 3-fold more cytotoxic (LC50 values ranged from 83 to 94
      microM) than NU1025 alone (LC50 > 900 microM). These data demonstrate that PARP
      inhibitors are effective resistance-modifying agents in human tumor cell lines
      and have provided a comprehensive assessment protocol for the selection of
      optimum combinations of anticancer drugs, PARP inhibitors, and cell lines for in
      vivo studies.

PMID- 10914736
TI  - Demethylating reagent 5-azacytidine inhibits telomerase activity in human
      prostate cancer cells through transcriptional repression of hTERT.
AB  - Telomerase activation is thought to be a critical step in cellular immortality
      and oncogenesis. Several reagents including differentiation-inducing and
      antineoplastic agents are known to inhibit telomerase activity, although the
      molecular mechanisms through which they inhibit telomerase activity remain
      unclear. Demethylating reagents have recently been used as potential
      antineoplastic drugs for some types of cancers including those of the prostate.
      In the present study, we examined the effect of the demethylating reagent 5
      azacytidine (5-aza-CR) on telomerase activity using cells of two prostate cancer
      cell lines, DU-145 and TSU-PR1. 5-aza-CR treatment significantly reduced
      telomerase activity in TSU-PR1 cells, but not in DU-145 cells, although growth
      inhibition was observed to a similar extent in both cell lines. Reverse
      transcription-PCR analyses revealed that inhibition of telomerase activity was
      accompanied by down-regulation of telomerase catalytic subunit (hTERT) mRNA
      expression. Transient expression assays showed that 5-aza-CR repressed the
      transcriptional activity of the hTERT promoter and that the E-box within the core
      promoter was responsible for this down-regulation. Western blot analyses revealed
      that 5-aza-CR reactivated p16 expression and repressed c-Myc expression in TSU
      PR1 cells but not in DU-145 cells. Overexpression of p16 in TSU-PR1 cells led to
      significant repression of c-Myc transcription. These findings suggest that 5-aza
      CR inhibits telomerase activity via transcriptional repression of hTERT, in which
      p16 and c-Myc may play a key role.

PMID- 10914737
TI  - 9-Nitrocamptothecin liposome aerosol treatment of melanoma and osteosarcoma lung
      metastases in mice.
AB  - The response rates of relapsed osteosarcoma and melanoma pulmonary metastases to
      traditional i.v. chemotherapeutic regimens have been disappointing. Direct drug
      delivery of chemotherapy to the lungs could increase the drug concentration in
      the tumor area and may offer a new therapeutic approach for these patients.
      Previous studies demonstrated that drugs delivered to the respiratory tract in
      liposomal formulation resulted in high pulmonary drug concentration, reduced
      systemic toxicity, and reduced dosage requirements compared with parenteral and
      oral administration. To determine whether this approach has utility against
      pulmonary metastases, the efficacy of aerosol therapy with liposome-encapsulated
      9-nitrocamptothecin (L-9NC) was determined using two different experimental lung
      metastasis models. C57BL/6 mice were treated the day after the i.v. injection of
      B16 melanoma cells with aerosol L-9NC for 1 h (153 microg 9-nitrocamptothecin/kg)
      for 5 days per week for up to 3 weeks. Aerosol L-9NC treatment resulted in a
      reduction in lung weights (P = 0.005) and number of tumor foci (P < 0.001).
      Visible tumor nodules were fewer and smaller in the 9-nitrocamptothecin-treated
      group than in untreated control mice (P < 0.001). Using a newly developed human
      osteosarcoma experimental metastasis model in nude mice, we demonstrated that
      aerosol L-9NC was also effective against established lung metastases. Aerosol
      therapy initiated on the ninth week after i.v. tumor injection and continued for
      8 or 10 weeks produced highly significant reductions in the number of animals
      with both visible and microscopic disease (P < 0.02), the total number of tumor
      foci in the lungs (P < 0.005), and the size of the individual tumor nodules (P <
      0.02). These data suggest that L-9NC aerosol therapy may offer significant
      advantage over existing methods in the treatment of melanoma and osteosarcoma
      pulmonary metastases.

PMID- 10914738
TI  - Augmentation of antitumor activity of 5-fluorouracil by interferon alpha is
      associated with up-regulation of p27Kip1 in human hepatocellular carcinoma cells.
AB  - Several clinical trials have demonstrated the effectiveness of combination
      therapy with 5-fluorouracil (5-FU) and IFN-alpha in colon cancer, hepatocellular
      carcinoma (HCC), and other malignancies. In our preliminary clinical studies, we
      have observed outstanding effects with this combination therapy in patients with
      advanced HCC. However, the underlying mechanism by which IFN-alpha modulates the
      effects of 5-FU is unknown. We, therefore, conducted a mechanistic study using
      two HCC cell lines, PLC/PRF/5 and HuH7. IFN-alpha significantly enhanced the
      growth inhibitory effect of 5-FU in PLC/PRF/5 cells but not in HuH7 cells, and
      the isobolographic analysis indicated that this effect was synergistic. Flow
      cytometric analysis showed a delay in the progression of G0-G1 to S phase in
      PLC/PRF/5, and a sustained, induction of the cyclin-dependent kinase inhibitor
      p27-Kip1 and down-regulation of cyclin D1 was observed. Moreover, increased
      expression of p27Kip1 was associated with reduced CDK-2-associated kinase
      activity. Another difference in the two cell types was that PLC/PRF/5 expressed
      abundant IFN receptors, but HuH7 did not. Apoptosis assays were not helpful in
      explaining the mechanism. Our results suggest that the synergistic effects of 5
      FU and IFN-alpha may in part be attributable to alterations in cell cycle
      progression via up-regulation of p27Kip1.

PMID- 10914739
TI  - Molecular and pharmacokinetic properties associated with the therapeutics of bcl
      2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin.
AB  - Bcl-2 is a key apoptosis-regulating protein that has been implicated in
      mechanisms of chemoresistance for a variety of malignancies by blocking
      programmed cell death. This study investigated the activity of the Bcl-2
      antisense oligodeoxynucleotide (AS ODN) G3139 combined with free doxorubicin (F
      DOX) or sterically stabilized liposomal doxorubicin (SL-DOX) to determine the
      role that drug pharmacodistribution properties may have on antitumor activity
      using a Bcl-2-expressing human breast solid tumor xenograft model. Administration
      of G3139 was able to delay the growth of MDA435/LCC6 cells compared with control
      ODN-treated animals; however, in all of the cases, tumors reestablished after AS
      ODN treatment. Western blot analyses of Bcl-2 levels of solid tumors showed a
      sequence-specific down-regulation of the Bcl-2 protein after four daily doses of
      G3139, which correlated with histological evidence of tumor cell death.
      Interestingly, the expression of Bcl-2 returned to pretreatment levels during the
      course of subsequent ODN administration, which suggested the development of
      resistance to continued Bcl-2 ODN treatment. The antitumor activity of ODN given
      in conjunction with either F-DOX or SL-DOX was also examined. The combination of
      G3139 and F-DOX was able to suppress the growth of MDA435/LCC6 cells beyond that
      obtained with either of the treatments given alone, indicative of synergistic
      action. Examination of the pharmacokinetics of F-DOX with systemic G3139
      administration revealed that elevated tumor drug DOX levels were obtained
      compared with DOX treatment in the absence of G3139. This effect was sequence
      specific and plasma DOX levels were unaffected by G3139 treatment, which
      indicated possible positive ODN-drug interactions at the tumor site. Combining
      G3139 with SL-DOX further increased the degree of antitumor activity. The
      improved efficacy of this combination was attributed to increased tumor drug
      levels that arise from the ability of SL-DOX to passively accumulate in solid
      tumors. These results suggest that additional benefits of Bcl-2 antisense ODN may
      be obtained when it is combined with liposomal formulations of anticancer drugs
      such as DOX.

PMID- 10914740
TI  - Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low
      clearance liposomal formulation of lurtotecan.
AB  - Lurtotecan is a clinically active water-soluble camptothecin analogue that has
      been formulated into a low-clearance unilamellar liposome, NX 211. Comparative
      studies between free drug and NX 211 have been performed assessing
      pharmacokinetics in nude mice, tissue distribution in tumor-bearing mice, and
      antitumor efficacy in xenografts. Compared with lurtotecan, NX 211 demonstrated a
      significant increase in plasma residence time and a subsequent 1500-fold increase
      in the plasma area under the drug concentration curve. The volume of distribution
      was also greatly restricted, suggesting altered tissue distribution. Evaluation
      of tissues 24 h after administration of either [14C]NX 211 or [14C]lurtotecan to
      ES-2 tumor-bearing mice demonstrated a 40-fold increase in radiolabeled compound
      in the tumors of NX 211-treated mice compared with mice treated with lurtotecan.
      In single-dose efficacy studies, NX 211 produced a consistent 3-fold or greater
      increase in therapeutic index compared with lurtotecan in both the KB and ES-2
      xenograft models. When compared at equitoxic levels in repeat-dose efficacy
      studies, NX 211 generated durable cures lasting >60 days and a 2-8-fold increase
      in log10 cell kill, compared with lurtotecan and topotecan, respectively.
      Together, these data demonstrate that NX 211 has significant therapeutic
      advantage over lurtotecan and that the improved antitumor activity is consistent
      with increased exposure and enhanced drug delivery to tumor sites.

PMID- 10914741
TI  - Effectiveness of combined interleukin 2 and B7.1 vaccination strategy is
      dependent on the sequence and order: a liposome-mediated gene therapy treatment
      for bladder cancer.
AB  - We have developed a novel liposome-mediated immunogene therapy using interleukin
      2 (IL-2) and B7.1 in a murine bladder cancer model. A carcinogen-induced murine
      bladder cancer cell line, MBT-2, was transfected with cationic liposome 1,2
      dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium
      bromide/dioleolylphosphatidylethanolamine and IL-2 plasmid. The optimized
      transfection condition generated IL-2 levels of 245-305 ng/10(6) cells/24 h, 100
      fold higher than the levels seen with retrovirus transfection. Ninety percent of
      the peak level of IL-2 production was maintained for up to 11 days after
      transfection. Animal studies were conducted in C3H/HeJ female mice with 2 x 10(4)
      MBT-2 cells implanted orthotopically on day 0. Multiple vaccination schedules
      were performed with i.p. injection of 5 x 10(6) IL-2 and/or B7.1 gene-modified
      cell preparations. The greatest impact on survival was observed with the day 5,
      10, and 15 regimen. Control animals receiving retrovirally gene-modified MBT-2/IL
      2 cell preparations had a median survival of 29 days. Animals receiving the IL-2
      liposomally gene-modified cell preparation alone had a median survival of 46
      days. Seventy-five percent of animals receiving IL-2 followed by B7.1 gene
      modified tumor vaccines were the only group to show complete tumor-free survival
      at day 60. All of these surviving animals rejected the parental MBT-2 tumor
      rechallenge and survived at day 120 with a high CTL response. In conclusion,
      liposome-mediated transfection demonstrates a clear advantage as compared with
      the retroviral system in the MBT-2 model. Multi-agent as opposed to single-agent
      cytokine gene-modified tumor vaccines were beneficial. These "targeted"
      sequential vaccinations using IL-2 followed by B7.1 gene-modified tumor cells
      significantly increased a systemic immune response that translated into increased
      survival.

PMID- 10914742
TI  - A polyphenolic fraction from grape seeds causes irreversible growth inhibition of
      breast carcinoma MDA-MB468 cells by inhibiting mitogen-activated protein kinases
      activation and inducing G1 arrest and differentiation.
AB  - In recent years, significant emphasis is being placed on identifying naturally
      occurring cancer preventive and interventive agents. In this regard, a
      polyphenolic fraction isolated from grape seeds (hereafter referred as GSP) has
      recently been shown by us and others to prevent tumorigenesis in mouse skin
      models. Chemical analysis of GSP has shown that it is largely constituted with
      procyanidins that are strong antioxidants. Breast cancer is the most common
      invasive malignancy and the second leading cause of cancer-related deaths in
      United States women. Accordingly, here we investigated the effect of GSP on
      mitogenic signaling and regulators of cell cycle and apoptosis as molecular
      targets for the growth arrest, apoptotic death, and/or differentiation of
      estrogen-independent MDA-MB468 human breast carcinoma cells. Treatment of cells
      with GSP (at 25-, 50-, and 75-microg/ml doses for 1-3 days) resulted in a highly
      significant inhibition (90% to complete, P < 0.001) of constitutive activation of
      mitogen-activated protein kinase (MAPK)/extracellular signal-regulated protein
      kinase1/2 in a dose-dependent manner after 72 h of treatment. Whereas GSP
      treatment of cells did not show a conclusive effect on MAPK/ JNK1 activation, a
      moderate to highly significant inhibition (15-70%, P < 0.1-0.001) of constitutive
      activation of MAPK/p38 was also observed in a dose-dependent manner as early as
      24 h of GSP treatment. GSP-treated cells also showed a strong induction (1.7-2.7
      fold, P < 0.001) of cyclin-dependent kinase inhibitor Cip1/p21 and a decrease (10
      50%, P < 0.1-0.001) in cyclin-dependent kinase 4. Consistent with these findings,
      GSP-treated cells resulted in their accumulation in G1 phase of the cell cycle in
      a dose-dependent manner. An irreversible growth inhibition (44-88%, P < 0.001)
      was also observed in 50 and 75 microg/ml GSP-treated cells in a time-dependent
      manner. Additional studies assessing the biological fate of GSP-treated cells
      showed that they do not undergo apoptotic death, as evidenced by a lack of DNA
      fragmentation, poly (ADP ribose) polymerase cleavage, and apoptotic morphology of
      the cells. A morphological change suggestive of differentiation was observed in
      GSP-treated cells that was further confirmed by a significant induction (1.7-2.6
      fold, P < 0.001), in both a dose- and time-dependent manner, in cytokeratin 8
      protein level, a marker of differentiation. An irreversible growth-inhibitory
      effect of GSP possibly via terminal differentiation of human breast carcinoma
      cells suggests that GSP and the procyanidins present therein should be studied
      more extensively to be developed as preventive and/or interventive agents against
      breast cancer in humans.

PMID- 10914743
TI  - Effects of SU101 in combination with cytotoxic agents on the growth of
      subcutaneous tumor xenografts.
AB  - SU101 (leflunomide, N-[4-(trifluoromethyl)-phenyl] 5-methylisoxazole-4
      carboxamide), an inhibitor of platelet-derived growth factor receptor signaling,
      has shown promising clinical activity in Phase I and II studies. Currently, SU101
      in combination with cytotoxic agents is in late-stage clinical development for
      the treatment of cancers. In previous reports, efficacy in vivo versus varied
      tumor xenografts was observed. As part of the preclinical development of SU101 as
      a cancer therapy, the combination of SU101 with cytotoxic agents was studied in
      athymic mice bearing small, established, s.c. human tumor cell xenografts of
      glioblastoma (SF763T cells), lung (Calu-6 cells), or head and neck (KB cells)
      origin. In the SF763T model, the combination of SU101 with carmustine resulted in
      a statistically significant growth inhibition of 74% compared with the vehicle
      control; this combination was more effective than either agent alone. In the Calu
      6 model, the combination of SU101, cisplatin, and etoposide resulted in a growth
      inhibition of 75% that was statistically greater than that of the vehicle-treated
      control group and groups treated with one or two agents. In the KB model, the
      combination of SU101, 5-fluorouracil, and cisplatin resulted in a statistically
      significant growth inhibition of 69% compared with the vehicle control. Treatment
      with one or two agents did not significantly inhibit growth in this model.
      Importantly, in addition to enhanced efficacy resulting from combination
      therapies, the combination treatments tested were well tolerated, as evidenced by
      lack of mortality. These data suggest that SU101 in combination with cytotoxic
      agents may provide clinical benefit and warrant further clinical investigation.

PMID- 10914744
TI  - Opposing effects of hypoxia on expression of the angiogenic inhibitor
      thrombospondin 1 and the angiogenic inducer vascular endothelial growth factor.
AB  - Tumor angiogenesis, the development of new blood vessels during malignant
      progression, is a regulated process that has both genetic and physiological
      controls. Physiologically, angiogenesis is stimulated by decreases in tissue
      oxygenation (i.e., hypoxia). We investigated the effect of hypoxia on the
      expression of two angiogenic factors reported to be genetically regulated by the
      p53 tumor suppressor gene: (a) the angiogenic inhibitor thrombospondin 1 (TSP-1);
      and (b) the angiogenic inducer vascular endothelial growth factor (VEGF).
      Analysis of rodent cells that differ in their p53 genotype (p53+/+ or p53-/-)
      indicated that in vitro exposure to hypoxia simultaneously suppressed TSP-1 and
      induced VEGF expression, regardless of the p53 genotype. On transformation of
      these cells with E1A and oncogenic H-ras, the basal level of TSP-1 expression was
      strongly diminished, whereas that of VEGF could still be induced by hypoxia.
      Consistent with these in vitro findings, sections of tumors derived from the
      transformed p53+/+ and p53-/- cells showed that VEGF protein overlapped with
      regions of hypoxia, whereas TSP-1 protein was below the limits of detection in
      tumor tissue. Using a panel of normal/immortalized and transformed human cells,
      it was found that the ability of hypoxia to inhibit TSP-1 expression depends on
      the cell type and/or the degree of transformation. In contrast, VEGF expression
      was induced by hypoxia in all of the human cell types examined. Together, these
      findings suggest that hypoxic and oncogenic signals could interact in the tumor
      microenvironment to inhibit TSP-1 and induce VEGF expression, promoting the
      switch to the angiogenic phenotype.

PMID- 10914745
TI  - Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2
      colon cancer cells.
AB  - Differentiation agents use existing cellular systems to induce neoplastic cells
      to regain a normal phenotype and/or to cause growth arrest and therefore may
      offer novel chemotherapeutic approaches to treating solid tumors. In this study,
      we demonstrate in Caco-2 colon cancer cells that the differentiation agent
      phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell
      differentiation, and a G1-S-phase block. The mechanism of this last effect is
      related to a PB-induced increase in p27Kip1, leading to a decrease in the
      activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S
      phase cell cycle transition. Consistent with the decreased CDK2 kinase activity,
      we also observed a decrease in the phosphorylation state of the retinoblastoma
      protein after PB treatment. This was associated with increased binding and
      consequent inactivation of E2F, a transactivator of genes that regulate the G1 to
      S phase cell cycle transition. These data suggest that the differentiation agent
      PB inhibits tumor growth by limiting the availability of active E2F, with a
      subsequent G1-S-phase block. Additional studies should show whether PB is a
      clinically effective therapeutic agent against colorectal cancer.

PMID- 10914746
TI  - The current state of evidence-based medicine.

PMID- 10914747
TI  - Multiple myeloma--evolving concepts of biology and treatment.

PMID- 10914748
TI  - The use of evidence-based medicine in the practice of consultant physicians.
      Results of a questionnaire survey.
AB  - BACKGROUND: Information is lacking about the extent to which Australasian
      physicians apply methods of evidence-based medicine (EBM) in routine practice.
      AIMS: To assess the frequency and predictors of use of EBM methods in a sample of
      consultant physicians in adult medicine. METHODS: Self-administered
      questionnaires were distributed to a convenience sample of 545 physicians from
      October 1998 to January 1999. RESULTS: One hundred and eleven questionnaires were
      returned (20% response rate). Ninety-eight (88%) respondents formulated five or
      less clinical questions per week; 69 (62%) undertook five or more evidence
      searches per week, the majority as MEDLINE searches involving therapeutic topics.
      Respondents identified insufficient time (74%), limited search skills (41%), and
      limited access to evidence (43%) as search impediments. In determining evidence
      quality, 37% frequently relied on global impressions, while 22% frequently
      applied explicit critical appraisal (p=0.008). Efficiency of literature searches
      was rated on average as good/very good by 18%, fair by 52% and poor by 30%. As a
      result of EBM, 47% frequently had confidence in pre-existing decisions increased,
      39% gained improved knowledge, and 5% altered clinical decisions. Frequently
      encountered inhibitors to changing practice were personal conservatism (40%),
      organisational constraints (40%), and interdisciplinary tensions (39%). Perceived
      weaknesses of EBM included: limited applicability to individual patients (26%);
      evidence deficiencies (25%); and too time consuming (13%). In making EBM more
      attractive, one third requested reliable evidence sources at the point of care.
      CONCLUSIONS: The application of EBM to routine practice by physicians is
      constrained by deficient EBM skills, limited access to evidence, lack of time,
      and cognitive and environmental factors. Targeted education in EBM and systems
      that quickly deliver high-quality evidence at the point of care are needed in
      realising the full potential of EBM to improve care.

PMID- 10914749
TI  - Hip fracture outcomes: quality of life and functional status in older adults
      living in the community.
AB  - BACKGROUND: People who return to living in the community after a hip fracture are
      considered to have the best outcome. However, their quality of life (QOL) and its
      relationship with function over the longer term have not been fully assessed.
      AIMS: This case control study of community dwelling subjects six to 12 months
      post hip fracture aims to investigate their QOL and functional independence.
      METHOD: The Short Form-36 (SF-36) was utilised to measure QOL. The Modified
      Barthel Index (MBI), the Frenchay Activities of Daily Living Index (FAI), the
      Timed 'Up & Go' (TUG), and the Berg Balance Scale (Berg) were used to measure
      functionality. RESULTS: Ninety-two subjects and 92 controls were recruited.
      Despite being age and gender matched, the hip fracture subjects scored
      significantly (p<0.05) worse than the controls in all measures of function. The
      fracture group was slower on the TUG (19 vs 10.5 seconds), had more difficulties
      with balance (46 vs 54 out of 56), and was less active and more dependent than
      the control group (FAI 24 vs 31 out of 42). The SF-36 has eight domains: physical
      function, role physical, bodily pain, mental health, role emotional, social
      function, general health and vitality. The control group had a higher (p<0.05)
      perception of their QOL in all domains. CONCLUSION: The effects of impaired
      balance and mobility along with reduced functional and social independence are
      reflected in the diminished QOL perceived by the fracture group. This indicates
      that many do not return to their pre-fracture lifestyle.

PMID- 10914750
TI  - Lp(a) and conventional risk profiles predict the severity of coronary stenosis in
      high-risk hospital-based patients.
AB  - AIMS: To explore predictive power of Lp(a), of conventional lipoprotein profiles
      and their carrier proteins, and of biometric measurements, for the presence and
      severity of angiographically documented coronary disease in high-risk patients,
      and to compare risk profiles in men and women. METHODS: We determined coronary
      artery disease (CAD) risk factors in 1308 Australian Caucasian patients (313
      women and 995 men) aged < or =65 years who consecutively underwent coronary
      angiography. RESULTS: In univariate analyses of the risk factors, lipid profiles,
      Lp(a), cigarette smoking, diabetes, hypertension and obesity were all higher in
      men and women with CAD and changed significantly with the number of significantly
      diseased vessels (> or =50% luminal obstruction). When stepwise logistic
      regression analysis was applied, age (OR 1.06, 95% CI: 1.04-1.09), TC/HDL-C (OR
      1.29, 95% CI: 1.15-1.45), male gender (OR 2.64, 95% CI: 1.67-4.16), hyperLp(a) (>
      or =300 mg/L) (OR 2.09, 95% CI: 1.42-3.07), lifetime smoking dose (OR 1.02, 95%
      CI: 1.01-1.03), diabetes (OR 2.19, 95% CI: 1.14-4.18) and waist/hip ratio (OR
      14.53, 95% CI: 1.21-174.90) were predictive of the disease. Both Lp(a) levels and
      percentage of hyperLp(a) increased linearly with the number of significantly
      diseased vessels. When the analyses were conducted in men and women separately,
      hyperLp(a), TC/HDL-C, lifetime smoking dose and age remained as significant
      predictors in both groups but the waist/hip ratio was only predictive in women.
      CONCLUSIONS: As Lp(a) is an independent predictor of the occurrence and extent of
      coronary stenosis and relevant to treatment options, we suggest that it should be
      measured routinely in the coronary risk profile assessment of high-risk patients.

PMID- 10914751
TI  - Advance care planning in residential care.
AB  - BACKGROUND: To provide optimal care for our ageing population, some form of
      advance care planning (ACP) is essential. Overseas data suggest that the process
      of ACP and the use of advance care directives (ACD) is suboptimal in residential
      care institutions. By comparison there are few Australian data. AIM: To study the
      process of ACP and the prevalence of ACD in residential care. METHODS: Cross
      sectional study using a questionnaire in the Hunter area, NSW, Australia.
      RESULTS: Very low levels of formal advance directives were found (available for
      only 0.2%). Only 1.1% of residents had 'no-CPR' orders documented in the medical
      record, while 5.6% had a formal guardian and 2.8% had an enduring guardian.
      Informal processes of advance planning were much more prevalent. Sixty-five per
      cent had a 'person responsible' recorded to make decisions for them while in 13%
      of cases, there was 'staff consensus' as to the optimal care for the patient.
      However, in 10.6% there was no clear process for medical decision making
      identified. CONCLUSIONS: Advanced directives are infrequently used in residential
      care. Further qualitative and quantitative studies are warranted to explore
      current processes of decision making.

PMID- 10914753
TI  - Diabetes mellitus and coronary heart disease--from prevention to intervention:
      Part I.

PMID- 10914752
TI  - The effect of acute hyperglycaemia on brachial artery flow mediated dilatation in
      normal volunteers.
AB  - BACKGROUND: Endothelial function is known to be abnormal in patients with
      diabetes and acute hyperglycaemia may play an aetiological role. AIMS: The aim of
      this randomised controlled study was to determine if acute systemic
      hyperglycaemia impairs endothelial function in normal subjects. METHODS:
      Endothelial function was assessed by the change in brachial artery diameter in
      response to forearm ischaemia using B-mode ultrasound in ten healthy subjects
      (eight male) aged 19-35 years. Brachial artery blood flow velocity and diameter
      were measured before and after five minutes of forearm ischaemia. Measurements
      were performed in the supine position after an overnight fast, before and after
      60 minute infusions of 0.9% saline or 10% dextrose. Measurements were made on two
      separate occasions at least 24 hours apart, and subjects were randomised to
      saline first or dextrose first. The largest diameter measured after ischaemia was
      divided by the resting arterial diameter to calculate percent dilatation of the
      artery from baseline, and is reported as flow-mediated dilatation (FMD). RESULTS:
      Dextrose infusion resulted in a significant rise in mean (SD) serum glucose 5.2
      (0.1) to 9.2 (0.3) mmol/L and insulin concentration 6.3 (1.4) to 20.6 (3.7) mU/L
      p<0.002. Brachial artery blood flow velocity and diameter increased significantly
      from baseline after ischaemia (p<0.002). Mean FMD (SEM) before and after infusion
      were not, however, significantly different (p=0.4) (pre-saline 7.3 [1.0]%, post
      saline 5.2 [1.5]% and predextrose 8.1 [2.0]%, post dextrose 5.9 [1.7]%).
      CONCLUSIONS: These data suggest that acute hyperglycaemia does not impair FMD in
      normal subjects.

PMID- 10914754
TI  - Advances in echocardiography.

PMID- 10914755
TI  - Health care workers and tuberculosis.

PMID- 10914756
TI  - Hydroxyurea induced skin ulceration in myeloproliferative disorders.

PMID- 10914757
TI  - Palliative care--new approaches to the problem of suffering.

PMID- 10914758
TI  - The anatomy and relations of evidence-based medicine.
AB  - Current tensions between evidence-based medicine (EBM) and some clinicians are
      counterproductive and unnecessary. The most contentious issues concern (a) the
      limitations of efficacy data from randomised trials as evidence; (b) differences
      in attitudes to medical diagnosis and clinical judgement; and (c) political
      concerns about the use of the concept of clinical evidence and guidelines to
      restrict physician autonomy. Health services research has evolved in response to
      a bureaucratic need to study health care, including clinical practice, in order
      to improve its effectiveness (defined mainly in terms of technological
      interventions), and to contain costs. Its perspective is from the top-down
      representing the interests of bureaucracy and managed care, and articulates with
      political demands for professional accountability and cost-containment. EBM has
      established its place as an important contributor to the methodological toolbox
      for health services research. There is a need for a corresponding coherent
      programme of clinical practice research which would locate EBM in the clinical
      environment beside quality assurance, the study of the appropriateness and
      effectiveness of interventions, and multidisciplinary research related to the art
      of medicine and supportive aspects of clinical care. EBM would then be seen as
      one organ in relation to many others making their contribution to the body of
      knowledge needed for clinical decisions and policy making. A 'centre for the
      study of clinical practice' would be an appropriate structure to support such a
      comprehensive programme of clinical practice research in a tertiary hospital. The
      bottom-up perspective of clinical practice research would complement the current
      top-down perspective of most health services research, providing information to
      doctors, patients and administrators concerning local quality of care and health
      outcomes, information which could also be aggregated for guidance of health
      policy makers. It would also represent the voice of the clinician in policy
      debates. Such a programme, located in the practice environment, would also foster
      mutual understanding, respect and cooperation between workers from different
      backgrounds.

PMID- 10914759
TI  - Body mass loss and fluid consumption in aquatic sport: a study of elite water
      polo players during competition.

PMID- 10914760
TI  - Melioidosis in a patient with idiopathic pulmonary haemosiderosis resident in
      Central Australia.

PMID- 10914761
TI  - The academic physician.

PMID- 10914762
TI  - How ill is mother, doctor, and should I come home?

PMID- 10914763
TI  - Cerebrospinal fluid (CSF) rhinorrhoea occurring six days after commencement of
      bromocriptine for invasive macroprolactinoma.

PMID- 10914764
TI  - Spontaneous pneumomediastinum--'ectasy': a hard pill to swallow.

PMID- 10914765
TI  - Primary vaginal non-Hodgkin's lymphoma after radiotherapy for Hodgkin's disease.

PMID- 10914766
TI  - Prostate cancer epidemic: early detection mandatory.

PMID- 10914767
TI  - The scientific advance of gastroenterology in the United States during the 20th
      century.

PMID- 10914769
TI  - Use of pancreaticogastrostomy for pancreatic reconstruction after
      pancreaticoduodenectomy.
AB  - After resection of the head of the pancreas, the distal remnant is typically
      telescoped into the jejunum. Recently, pancreaticogastrostomy has re-emerged as a
      useful alternative, as the anastomosis is easy and without tension. The results
      of pancreaticogastrostomy in 10 consecutive patients is reviewed, as is the
      literature of both the technique and the physiology of the procedure. In the
      current series, mean +/- SEM age was 65 +/- 2.3 years. Extended
      pancreaticoduodenectomy was performed in two patients, pylorus-preserving in
      eight. Mean tumor size was 3.9 +/- 1.1 cm (range, 1.5-7.5 cm), mean operative
      time was 6.5 +/- 0.5 hours. Intraoperatively, 7.6 +/- 0.8 L of fluid was given,
      only two patients were transfused. The mean length of stay was 9.4 +/- 1.8 days.
      There were no anastomotic leaks, no deaths, and two patients developed temporary
      gastric ileus. There are now 841 pancreaticogastrostomies reported in the
      literature, with a leak rate of 3.1% and a death rate of 2.6%.
      Pancreaticogastrostomy is easy to perform, safe, and useful even after extended
      Whipple.

PMID- 10914768
TI  - Prophylactic antibiotic therapy in the management of acute pancreatitis.
AB  - Studies done in the early 1970s came to the conclusion that antibiotic
      prophylaxis was not useful in the management of acute pancreatitis. However,
      these studies suffered from the drawback of using antibiotics that had poor
      penetration into the pancreas. In addition, the design of these trials were
      faulty. With the advent of new information and the availability of better
      antibiotics, the picture is changing. Recent studies have suggested that
      antibiotic prophylaxis is useful in decreasing the incidence of infection in
      patients with severe pancreatitis. Of the antibiotics that have been tested,
      imipenem appears to be the most promising.

PMID- 10914770
TI  - Recurrent severe gastrointestinal bleeding complicating treatment of morbid
      obesity.

PMID- 10914772
TI  - Endoscopic placement of Sengstaken-Blakemore tube.
AB  - A Sengstaken-Blakemore (SB) tube, when used approximately, still has a place in
      the management of acute variceal bleeding. Due to a number of reported
      complications from the misplacement of this tube, an x-ray localization before
      full inflation of the gastric balloon is recommended as the standard of care.
      Here, we report a new technique of SB tube placement with endoscopic confirmation
      in three patients. This technique is easy, accurate, and can be performed in any
      unit where a patient with variceal bleeding can be managed. Because it cuts down
      on the need for an x-ray or ultrasound confirmation, this technique may well
      become the "standard of care" among the practicing gastroenterologists.

PMID- 10914771
TI  - What predictive parameters best indicate the need for emergent gastrointestinal
      endoscopy after foreign body ingestion?
AB  - Our aim was to determine what parameters may be used to indicate an emergent
      endoscopy after foreign body (FB) ingestion and to ascertain how often FBs are
      found endoscopically. Demographic data, gastroesophageal antecedents, clinical
      and endoscopic data, and complications were obtained. We examined 122 patients
      endoscopically. The onset of symptoms was immediate after FB ingestion in 93% of
      patients. Dysphagia was the most frequent symptom (66%), with the pharynx the
      most frequent location of impaction (71%). Endoscopy confirmed the presence of
      FBs in 52% of patients. Extraction was performed in 78%. The immediate onset of
      symptoms, dysphagia, and the absence of pharynx localization of impaction were
      predictive indicators of a positive FB finding (p < 0.05), with diagnostic
      sensitivity of 86% and specificity of 63%. Upper endoscopy should be performed in
      all patients with FB ingestion, even though no FB was found in 48%.

PMID- 10914773
TI  - Prevalence of Helicobacter pylori infection in Argentina: results of a nationwide
      epidemiologic study. Argentinean Hp Epidemiologic Study Group.
AB  - Our aim was to assess the prevalence of Helicobacter pylori (Hp) infection in
      Argentina, in the general population and by age groups, and to determine the
      value of various epidemiologic variables as predictors of Hp infection. The study
      comprised 754 subjects (443 women 158.7%], 311 men [41.3%]) from both genders,
      consecutively recruited from health centers where patients were undergoing
      routine medical analyses. Average age was 32 +/- 22 years. The pediatric group
      included subjects < or =18 years of age (n = 261). Stratification was based
      primarily on climatic factors and secondarily on sanitary and demographic
      considerations. Hp infection status was assessed through a quick serologic test.
      The overall Hp infection prevalence in Argentina was 35.7 +/- 3.8%. The age was
      statistically significant using a multiple regression test (p < 0.01).
      Furthermore, the socioeconomic (p < 0.05) and educational level (0 < 0.01) in the
      adults and the water sources (p < 0.01) in the pediatric group were all
      statistically significant according the multiple regression test. The overall Hp
      infection prevalence in Argentina was 35.7 +/- 3.8%. Age was a predictor of Hp
      infection status. There is evidence of low infection prevalence in children. a
      higher prevalence in adolescents, and a more noticeable increase at 40 years of
      age. Furthermore, the socioeconomic and educational level in adults and the water
      sources in the pediatric group explained, in part, the occurrence of Hp
      infection.

PMID- 10914774
TI  - Clinical and histologic predictors of Helicobacter pylori infection recurrence.
AB  - Factors influencing Helicobacter pylori infection recurrence still have not been
      fully clarified. The aim of this study was to determine whether, after
      eradication of H. pylori, any clinical or histologic features could yield
      information on infection relapse. We enrolled in the study 72 patients
      successfully treated for H. pylori infection by either dual (n = 49) or triple (n
      = 23) therapy. H. pylori eradication was defined as a negative bacterial finding
      by rapid urease test and histologic assessment at least 4 weeks after cessation
      of therapy. Upon eradication, gastritis grading was performed and patients were
      asked to return for an endoscopic control 6-8 months later. The recurrence of H.
      pylori infection was observed in 12 of 72 (16.7%) patients. The infection
      recurrence rate resulted significantly higher in nonulcer dyspepsia patients (p =
      0.01 ) and in women (p = 0.03), whereas infection relapse did not differ between
      patients treated with dual or triple therapy. There was a strong (p = 0.0001 )
      relationship between the persistence of chronic active gastritis after H. pylori
      eradication and recurrence of infection, whereas gastritis grade and metaplasia
      were not related to recurrence. In conclusion, this study found that H. pylori
      infection recurrence after successful dual or triple therapy is fairly high and
      that gastroduodenal disease, gender, and gastritis activity seem to affect
      infection relapse.

PMID- 10914775
TI  - Prevalence and risk factors of Helicobacter pylori-negative peptic ulcer: a
      multicenter study.
AB  - Peptic ulcer disease (PUD) has been described in the absence of Helicobacter
      pylori (Hp) infection, suggesting that different factors are involved in its
      etiopathogenesis. We investigated prevalence and characteristics of Hp-negative
      (Hp-) PUD in an area of Northern Italy and calculated the rate of Hp-positive
      (Hp+) patients with PUD in whom Hp might be coincidental and not causal. Four
      hundred nine consecutive patients with endoscopically diagnosed PUD were enrolled
      in seven hospitals. Hp infection was assessed by rapid urease test and histologic
      examination. The attributable risk percentages in different age groups were
      calculated by appropriate formulas. Of 409 patients, 31 (7.6%) were Hp- (gastric,
      8.3%; duodenal, 7.6%). Age, nonsteroidal antiinflammatory drug (NSAID)
      consumption, and complication rates were significantly higher in Hp-than Hp+
      patients with duodenal ulcers (DUs). Of the Hp-patients with DU, 58% did not use
      NSAIDs. In patients with Hp+ DU, the attributable risk percentage for Hp
      infection in patients aged <40 years, 40-60 years, or >60 years was 98%, 88%, and
      66%, respectively. The prevalence of Hp- PUD was about 8%, mainly unrelated to
      any known etiologic factor. In about one-third of Hp+ patients with PUD aged over
      60 years, Hp infection might be coincidental and not causal.

PMID- 10914776
TI  - Serum anti-Lewis X antibody is not elevated in patients with gastric cancer
      infected with Helicobacter pylori.
AB  - Lipopolysaccharides of Helicobacter pylori express Lewis X similar to that
      occurring in gastric mucosa. Patients infected with H. pylori produce anti-Lewis
      X antibodies. The aim of this study was to examine whether anti-Lewis X antibody
      was associated with the development of gastric cancer, particularly intestinal
      type cancer. Serum sample was collected from 98 patients with early gastric
      cancer and 98 gender- and age-matched control subjects who underwent endoscopy.
      Histologically, 77 cancers were of the intestinal type. Titers of anti-H. pylori
      and anti-Lewis X immunoglobulin G (IgG) antibodies were assayed by enzyme-linked
      immunosorbent assay. The mean titer of Lewis X antibody was 0.097 in patients
      with gastric cancer and 0.110 in matched control subjects (not significant). In
      72 H. pylori-seropositive patients with intestinal type cancer and their matched
      H. pylori-seropositive controls, mean titer was 0.115 and 0.107, respectively
      (not significant). The odds ratio for the risk of gastric cancer if Lewis X
      antibody was high titer was 0.93 (95% CI 0.43-2.00). The odds ratio for the risk
      of intestinal type gastric cancer in patients with H. pylori infection if Lewis X
      antibody was high titer was 1.10 (95(% CI, 0.46-2.62). Anti-Lewis X antibody does
      not seem to be associated with the development of gastric cancer, even the
      intestinal type cancer.

PMID- 10914777
TI  - Evaluation of pancreatic exocrine function using pure pancreatic juice in
      noninsulin-dependent diabetes mellitus.
AB  - To investigate the pancreatic exocrine function in noninsulin-dependent diabetes
      mellitus (type 2 DM), we evaluated the pure pancreatic juice obtained by
      endoscopic cannulation of the main pancreatic duct in 13 healthy control subjects
      and 22 patients with type 2 DM who had no evidence of pancreatic disease. Samples
      of pancreatic juices were collected in six fractions for 30 minutes at 5-minute
      intervals after an intravenous bolus injection of secretin (0.25 CU/kg) and
      cholecystokinin-8 (CCK) (40 ng/kg). The responses of plasma glucose, insulin, and
      C-peptide to intravenous administration of glucose (50%, 40 mL) were measured.
      The levels of plasma insulin and C-peptide levels in type 2 DM were the same as
      in healthy controls in the basal state but did not further increase in response
      to an intravenous glucose. This suggested that patients with type 2 DM had
      insulin secretion defect rather than insulin deficiency. Pancreatic secretions
      including volume, bicarbonate, and protein output in response to stimulation with
      secretin, and CCK were significantly reduced when compared to the healthy
      controls. We conclude that patients with type 2 DM exhibit impairment of
      pancreatic exocrine secretion and that this impairment might not be related to
      insulin deficiency. Therefore, we recommended that careful evaluation for
      exocrine pancreatic function in type 2 diabetics who have any clinically
      suspicious symptoms of pancreatic insufficiency.

PMID- 10914778
TI  - D-xylose kinetics and hydrogen breath tests in functionally anephric patients
      using the 15-gram dose.
AB  - Malabsorptive evaluation in renal failure is difficult because most absorptive
      testing requires urinary collections. Kinetic analysis of d-xylose absorption and
      d-xylose breath testing were performed in an effort to establish an effective
      absorption test in functionally anephric patients. We studied 13 fasting renal
      failure patients with no diarrhea or symptoms suggesting malabsorption on two
      separate nondialysis days after they received 15 g oral d-xylose on day 1 and 10
      g IV on day 2. Serum collections were used to calculate the kinetic rate
      constants and extent of d-xylose absorption. After the oral d-xylose, end
      expiratory breaths were collected every 15 minutes for 3 hours and were analyzed
      for H2 with gas chromatography. Five subjects also allowed upper endoscopy and
      duodenal biopsy. The mean absorption rate constant (Ka) and bioavailability (F)
      were similar to published values for normal subjects using the 15-g dose (0.936
      min(-1); range, 0.227-1.96; and 74%, range 46-99, respectively). Of the patients,
      12 had normal 1-hour serum d-xylose concentrations (>20 mg/dL). There was no
      clear inverse correlation between the rate constant for absorption or
      bioavailability and peak breath hydrogen or the area under the curve for breath
      H2 versus time. Using 15 g oral d-xylose, mean bioavailability and absorption
      rate constants are normal in functionally anephric patients with no clinical
      evidence of malabsorption. Three patients had elevated breath peak H2
      concentrations, but there was no clear inverse correlation between
      bioavailability and the breath H2 values. A 1-hour serum dxylose concentration
      >20 mg/dL may be considered normal in this patient group, similar to patients
      with normal renal function.

PMID- 10914779
TI  - Diarrhea as a side effect of mesalamine treatment for inflammatory bowel disease.
AB  - Tablets of coated 5-aminosalicylate (5-ASA) called mesalazines are among the most
      widely prescribed preparations for the treatment of colitis, including
      ulcerative, Crohn's disease (CD), collagenous and lymphocytic colitis, and-to a
      lesser extent-CD of the small bowel. Mesalamines have, to a large extent,
      replaced the parent drug sulfasalazine because they produce fewer side effects.
      Although mesalamines have been known from earlier studies to produce occasional
      diarrhea, the true incidence of this effect is not known and is not always
      recognized. We are presenting the cases of five patients in whom oral mesalamines
      produced severe and persistent diarrhea-made worse by increasing doses of the
      drug-and intensified the colitis in two. Recognition of the problem is by symptom
      analysis after careful history taking. Changing the therapeutic regimen or
      discontinuing the medication is usually required to reverse this potentially
      debilitating and occasionally life-threatening side effect.

PMID- 10914780
TI  - Orocecal transit time and bacterial overgrowth in patients with Crohn's disease.
AB  - Bacterial overgrowth is frequent in patients with Crohn's disease (CD) and can
      contribute to symptoms. Motility abnormalities can predispose to bacterial
      overgrowth. The hydrogen (H2) and methane (CH4) breath test is a sensitive and
      simple tool for the diagnosis of bacterial overgrowth and for the evaluation of
      orocecal transit time (OCTT). In this study, we investigated the prevalence of
      OCTT modifications and bacterial overgrowth in a series of consecutive adult
      patients with CD. In 43 healthy subjects and 67 patients with CD. we performed
      the lactulose breath test using a gas analyzer that offers the opportunity of
      measuring both H2 and CH4. Of the patients, 24 had undergone an ileocolic
      resection before the test with ablation of the ileocecal valve. At the time of
      the test 15 patients had active disease, whereas in 52 subjects the disease was
      quiescent. Fifty-seven patients and forty controls were evaluable for OCTT and
      bacterial overgrowth. In 10 patients and in 3 controls, no H2 or CH4 peak was
      recorded during the 8-hour test. Out of 57 patients, 13 (23%) were affected by
      bacterial overgrowth. The prevalence of bacterial overgrowth was higher in
      patients with previous surgery (30%) than in nonoperated patients (18%). In all
      patients with bacterial overgrowth, an antibiotic treatment induced a
      normalization of the test and an improvement of the symptoms. We observed a
      longer OCTT in the patients compared to controls, although this difference was
      not statistically significant (154 +/- 45 vs. 136 +/- 45 minutes). OCTT was
      significantly longer compared to controls in the 14 CD patients with previous
      ileocolic resection ( 180 +/- 53 vs. 136 + 45 minutes; p < 0.004). In conclusion,
      we found that a significant proportion of unselected patients with CD has
      bacterial overgrowth and prolongation of OCTT. We suggest that the modifications
      in OCTT in patients with CD can predispose to bacterial overgrowth. The lactulose
      breath test is a simple method that can be more widely used in patients with CD.

PMID- 10914781
TI  - Pathologic characteristics of colorectal cancer in the elderly: a retrospective
      study of 947 surgical cases.
AB  - To determine the pathologic characteristics of colorectal cancer in the very old,
      a retrospective study of 947 consecutive Japanese patients aged > or =65 with
      1,039 lesions were examined. Pathologic findings in the very old group (>85
      years, n = 140) were compared with those in the younger groups; young-old group
      (65-74 years, n = 352) and middle-old group (75-84 years, n = 455). Although
      male:female ratio significantly decreased with advancing age, reaching 1:1.8 in
      the very old group, the relative odds of colorectal cancer in men were higher
      than that in women in all age groups. In the very old group, cancer of the
      proximal colon (proximal to the splenic flexure) accounted for 52% in women and
      37% in men, being significantly higher than those in the younger groups. Proximal
      colonic cancers increased with advancing age in both genders. Higher proportions
      of poorly differentiated adenocarcinoma, mucinous carcinoma, cancer >5 cm in
      size, and protruding type cancer were present in the very old group, although
      these kinds of tumors typically occur in the proximal colon. The incidence of
      multiple cancers in the large intestine was not different among any age group
      (average, 8.6%). These results indicated that, even in the very old, colorectal
      cancers showed marked proximal excess, being explained by effect of both age and
      gender, and that the proximal shift may influence the proportion of histologic
      type and size of the tumor. These findings have important implications for
      screening and diagnosis of colorectal cancer in the elderly.

PMID- 10914782
TI  - Insignificant role of hepatitis G virus infection in patients with liver enzyme
      elevations of unknown etiology.
AB  - Hepatitis G virus (HGV) may cause acute and chronic infection in humans but its
      role in parenchymal liver injury and chronic hepatitis is obscure. In this study,
      the importance of HGV was investigated in patients with elevated
      aminotransferases alanine transaminase/aspartate transaminase (ALT/AST) levels of
      unknown etiology. We included 56 patients with elevated ALT/ AST levels of
      unknown etiology and 81 healthy controls in the study. HGV RNA was investigated
      by the reverse transcription polymerase chain reaction. The other possible causes
      of transaminase elevation were excluded with detailed biochemical and serologic
      tests. Liver biopsy was performed on 47 patients for histologic examination. HGV
      RNA was detected in only two patients (3.3%) and in one control (1.2%). There was
      no statistical difference between the groups. Liver biopsy revealed minimal
      inflammatory changes and steatosis in HGV RNA-positive patients. These
      observations indicated that HGV prevalence is not different from that of the
      general population in patients with liver transaminases elevation of unknown
      etiology. The role of this novel virus in the pathogenesis of chronic liver
      injury of unknown etiology appears insignificant in our geographic area.

PMID- 10914783
TI  - Spontaneous fungal peritonitis in patients with hepatitis B virus-related liver
      disease.
AB  - Spontaneous bacterial peritoneal infections is recognized as a very common
      complication of cirrhotic ascites, but isolation of fungus in pure culture from
      ascitic fluid is relatively rare, even more so in the human immunodeficiency
      virus (HIV)-negative or nonimmunocompromised hosts. We describe two patients of
      spontaneous fungal peritonitis where the isolate was Cryptococcus neoformans.
      Both cases suffered from hepatitis B virus (HBV) infection. The clinical and
      laboratory profiles of both patients were similar to those of conventional
      spontaneous bacterial peritonitis. We suggest that it would be prudent to
      heighten clinical suspicion for fungal peritonitis in such cases.

PMID- 10914784
TI  - Hepatocellular carcinoma complicating liver cirrhosis in type IIIa glycogen
      storage disease.
AB  - Type III glycogen storage disease (GSD III) is an autosomal recessive disorder
      characterized by the accumulation of abnormal glycogen in the liver and, in most
      patients, in the muscle. Although liver fibrosis is a well-known consequence of
      GSD III, until now only eight cases of liver cirrhosis and two cases of
      hepatocellular carcinoma have been described in patients affected by this
      disease. In this case report, the authors describe the clinical history of a
      patient affected by GSD III who developed severe liver disease during her adult
      life, progressing from fibrosis to cirrhosis and finally to hepatocellular
      carcinoma. Until now, the hepatic involvement in GSD III has been considered by
      most authors as mild and almost always self-limiting. This report, together with
      the previously published cases, clearly indicates that severe and progressive
      liver disease may complicate this metabolic disorder. These observations advise a
      careful hepatologic follow-up of patients affected by GSD III.

PMID- 10914785
TI  - The role of dual-phase enhanced helical computed tomography in difficult
      intestinal bleeding.
AB  - We report a case of leiomyoma of the small bowel presenting with massive
      gastrointestinal (GI) bleeding that was diagnosed using dual-phase enhanced
      helical computed tomography (CT) in the preoperative period. A 68-year-old man
      was admitted to our hospital because of recurrent rectal bleeding.
      Gastroduodenoscopic and total colonoscopic examination results were negative;
      however, the patient continued to show bloody stool. Dual-phase enhanced helical
      CT was subsequently performed. CT revealed a hypervascular tumor, with evident
      extravasation of the contrast medium in the bowel lumen. We were successful in
      establishing the point of bleeding. Exploratory laparotomy was performed the same
      day. A solid round extraluminal mass was found at the proximal jejunum. Bleeding
      was observed over the serosal side of this tumor and segmental resection of the
      tumorous small intestine was performed. Pathologic examination revealed
      leiomyoma. Enhanced helical CT proved to be useful in localizing active GI
      bleeding.

PMID- 10914786
TI  - Gastric adenocarcinoma with a yolk sac component: a case report and review of the
      literature.
AB  - Gastric yolk sac tumors (YST) are very rare and are mainly reported in elderly
      people. We present a case of a 36-year-old man with a poorly differentiated
      gastric cancer showing a mixture of adenocarcinoma and yolk sac tumor that
      metastasized to Virchow's node. Both biopsies, Virchow's node and gastric tumor,
      contained areas of adenocarcinoma and yolk sac tumor that stained strongly
      positive for alpha fetoprotein (AFP) by the immunohistochemistry method. A high
      level of serum AFP (38,200 ng/mL) was also noted in this case. The response to
      chemotherapy in this case of mixed gastric yolk sac tumor and adenocarcinoma was
      not as favorable as would be expected in a pure primary germ cell tumor.

PMID- 10914787
TI  - Thoracoscopic enucleation of an esophageal leiomyoma.
AB  - A series of reports in the literature suggest that video assisted thoracoscopic
      resection of an esophageal leiomyoma offers distinct advantage over open
      approach. We describe a patient with esophageal leiomyoma who underwent surgical
      resection via thoracoscopic approach using four thoracic trocars. The
      postoperative period was uneventful and the patient was discharged on
      postoperative day 3.

PMID- 10914788
TI  - Dilated cardiomyopathy due to anticardiolipin syndrome in association with celiac
      sprue.

PMID- 10914789
TI  - Transient "polyposis coli".

PMID- 10914790
TI  - The watermelon stomach: successful treatment by monopolar electrocoagulation and
      endoscopic injection of polidocanol.

PMID- 10914791
TI  - "Checkerboard" assessments of periodontal microbiota and serum antibody
      responses: a case-control study.
AB  - BACKGROUND: We explored the association between subgingival microbial profiles
      and serum IgG responses to periodontal microbiota in relation to clinical
      periodontal status. METHODS: One hundred thirty-one (131) periodontitis patients
      aged 29 to 74 years (mean 51.8) were age- and gender-matched with 74
      periodontally intact controls (range 26 to 77, mean 49.3). Smoking habits and
      health history were recorded and assessments of plaque, bleeding on probing,
      probing depth, and attachment level were performed at 6 sites per tooth on all
      present teeth, excluding third molars. Subgingival plaque samples were obtained
      from each tooth in one upper and one lower quadrant (maximum 14 samples/subject;
      2,440 samples total) and analyzed with respect to 19 species by means of whole
      genomic DNA probes. Serum IgG antibodies against the same 19 species were
      assessed by an immunoassay. RESULTS: Cases displayed an average of 22.7 teeth,
      20.3 sites with probing depth > or =6 mm, and 18.9 sites with attachment loss >
      or =6 mm. Corresponding figures for controls were 27.1, 0.1, and 1.0,
      respectively. Heavy smoking was 3 times more frequent among cases than controls
      (32.1% versus 9.6%). Higher levels of Porphyromonas gingivalis, Porphyromonas
      endodontalis, Prevotella intermedia, Prevotella nigrescens, Prevotella
      melaninogenica, Bacteroides forsythus, Fusobacterium nucleatum, Treponema
      denticola, Eubacterium nodatum, Peptostreptococcus micros, and Campylobacter
      rectus were found in cases and higher levels of Eikenella corrodens, Veillonella
      parvula, and Actinomyces naeslundii in controls. Cases displayed higher IgG
      levels against P. gingivalis and Actinobacillus actinomycetemcomitans, while
      controls displayed higher levels against F. nucleatum, T. denticola, E. nodatum,
      and Capnocytophaga ochracea. Positive correlations between bacterial colonization
      and antibody responses were identified for 9 species in controls. In cases,
      however, statistically significant correlations were observed for only 3 species
      out of which only one was positive (V. parvula). Both bacterial levels and
      antibody responses declined in ages over 55 years. A logistic regression
      employing selected elements of bacterial colonization and antibody responses as
      independent variables resulted in 81.1% correct diagnosis, with sensitivity of
      83.1%, specificity of 77.8%, positive predictability of 86%, and negative
      predictability of 73.7%. Smoking did not reach statistical significance in this
      model. CONCLUSION: A combined microbial colonization/antibody response profile
      can effectively discriminate between periodontitis patients and periodontally
      intact controls.

PMID- 10914792
TI  - Metabolic diseases and their possible link to risk indicators of periodontitis.
AB  - BACKGROUND: During the last few years, risk assessment has become one of the main
      topics of periodontal research. Therefore, the aim of this study was to determine
      whether a predisposition to metabolic disorders such as diabetes mellitus (in the
      absence of diagnosed diabetic disease) or hyperlipidemia may be risk indicators
      for periodontitis. METHODS: One hundred patients ranging in age from 40 to 70
      years were examined. The patients were classified as having impaired glucose
      tolerance (IGT) but no manifest diabetes (56 patients), hyperlipidemia (17
      patients, HL), or normal metabolic status (27 control patients). Probing depth
      (PD), attachment level (AL), plaque index (PI), and gingival bleeding on probing
      (BOP) were recorded. Serum antibody titers (SAT) to A. actinomycetemcomitans
      (A.a.), P. intermedia (P.i.), and P. gingivalis (P.g.) were determined by enzyme
      linked immunosorbent assay (ELISA). Pooled subgingival plaque samples were
      analyzed using indirect immunofluorescence to detect the same organisms. In
      addition, respiratory burst activity of peripheral polymorphonuclear leukocytes
      (PMN) was evaluated by chemiluminescence (CL). RESULTS: No significant
      differences were observed between the IGT group and normal controls in the
      following parameters: 1) percentage of sites exhibiting BOP; 2) mean PI; 3) mean
      PD and AL; 4) percentage of periodontal microorganisms; and 5) increased SAT. The
      IGT probands exhibited a significantly higher mean serum level of triglycerides,
      as well as higher formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMN
      chemiluminescence than the control group. Patients with hyperlipidemia (HL)
      showed a significantly higher number of sextants with increased PD (73.4%) than
      the control group (50.6%). Similar results were obtained when comparing the
      percentage of all sites with increased PD (HL = 16.7%, control 12.3%). The mean
      FMLP-stimulated CL in patients with hyperlipidemia was significantly higher than
      the control group. When looking at all patients, there was a small but
      statistically significant correlation between PD and lipid levels. In addition, a
      significant correlation was observed between lipid serum levels and the FMLP
      stimulated chemiluminescence. CONCLUSIONS: These findings suggest that abnormal
      glucose tolerance, which is a predisposing factor for diabetes mellitus, does not
      appear to be a risk indicator for periodontal disease. On the other hand,
      impaired lipid metabolism does seem to be a risk indicator for periodontitis.

PMID- 10914793
TI  - Guided tissue regeneration associated with bovine-derived anorganic bone in
      mandibular class II furcation defects. 6-month results at re-entry.
AB  - BACKGROUND: The use of graft materials with guided tissue regeneration (GTR) in
      Class II furcation defects is aimed at improving the outcome of the regenerative
      technique. In this regard, however, there are a limited number of studies
      discussing the results obtained when GTR and graft materials are used in the
      treatment of Class II furcation defects. Furthermore, most studies employ either
      allogeneic or autogenous materials. The present trial sought to determine whether
      the use of a bovine-derived anorganic bone (ABB) in conjunction with GTR
      influenced the outcome of mandibular Class II furcation treatment. METHODS: This
      study included 14 patients who provided 15 pairs of similar periodontal defects.
      Each defect was randomly assigned to treatment with either a cellulose membrane
      in combination with bovine-derived anorganic bone (GTR+ABB) or membrane alone
      (GTR). Following basic therapy, baseline measurements were recorded including
      probing depth (PD), clinical attachment level (CAL), and gingival margin position
      (GMP). Hard tissue measurements were performed during surgery to determine
      alveolar crestal height (CEJ-AC), and vertical (VDD) and horizontal defect depth
      (HDD). Membranes remained in position for at least 4 weeks. After 6 months, all
      sites were re-entered and soft and hard tissue measurements were recorded.
      RESULTS: Both surgical procedures resulted in statistically significant probing
      depth reduction and gain in clinical attachment levels, with no significant
      difference between groups. Gingival recession was more pronounced in the GTR+ABB
      group (0.87 +/- 0.83 mm), but not statistically different from the GTR group
      (0.46 +/- 1.19 mm). Vertical defect resolution was significant in both groups
      (GTR: 1.60 +/- 1.50 mm; GTR+ABB: 1.80 +/- 2.11 mm), without differences between
      groups. Only horizontal furcation resolution (GTR: 2.47 +/- 0.99 mm; GTR+ABB:
      3.27 +/- 1.39 mm) was significantly different between groups (P <0.05).
      CONCLUSIONS: The use of ABB with GTR techniques improved horizontal defect
      resolution in mandibular Class II furcation defects, but did not yield superior
      results regarding soft tissue changes when compared to sites treated with GTR
      alone. Evaluation of a larger sample could indicate differences and advantages
      between the evaluated approaches and confirm the real necessity of associating
      filling materials with GTR.

PMID- 10914795
TI  - Immediate versus non-immediate implantation for full-arch fixed reconstruction
      following extraction of all residual teeth: a retrospective comparative study.
AB  - BACKGROUND: Immediate implants placed into fresh extraction sites are considered
      a predictable and acceptable procedure. The main biological advantage is the
      preservation of bone height and width. However, there is no direct proof of the
      clinical and surgical importance of this. The purpose of this study was to
      evaluate the correlation between implant dimensions, anatomic factors, and
      survival rates of immediate versus non-immediate implants. METHODS: From 1989 to
      1996, 380 implants (117 immediate and 263 non-immediate) were placed in 43
      patients (50 jaws) following extraction of all residual teeth. A total of 253
      implants were placed in the maxilla and 127 in the mandible, with a mean of 7.65
      and 7.9 per jaw, respectively. Of the implants, 31% were placed immediately into
      fresh extraction sites. RESULTS: Total 5-year cumulative survival rate (CSR) was
      92%, mandibular 96% and maxillary 90%. Immediate implants had a better 5-year CSR
      (96%) versus non-immediate implants (89.4%). The maxilla mainly contributed to
      this difference (95% versus 88%). The mean potential contact surface area (PCSA)
      was 230 mm2. Implants with significantly higher values yielded a higher 5-year
      CSR in the maxilla (96.6% versus 82.9%). Immediate implants in the posterior
      maxilla had a 100% 5-year CSR versus 72% with the non-immediate implants.
      CONCLUSIONS: 1) Implant-supported fixed ceramo-metal prosthesis is a predictable
      treatment modality for edentulous patients; 2) factors favorably affecting the
      survival of implants placed to support full-arch ceramo-metal prosthesis include
      immediate implantation, higher PCSA values, and implant location; 3) immediate
      implantation exerts its effect through higher PCSA values and by a compensatory
      effect to bone quality; 4) immediate implantation does not carry additional
      morbidity; and 5) potential contact surface area (PCSA) is a reliable mean that
      accurately represents implant dimensions and may replace length and diameter in
      future studies.

PMID- 10914794
TI  - Evidence for the role of highly leukotoxic Actinobacillus actinomycetemcomitans
      in the pathogenesis of localized juvenile and other forms of early-onset
      periodontitis.
AB  - BACKGROUND: Actinobacillus actinomycetemcomitans leukotoxin is thought to be an
      important virulence factor in the pathogenesis of localized juvenile and other
      forms of early-onset periodontitis. Some highly leukotoxic A.
      actinomycetemcomitans strains produce 10 to 20 times more leukotoxin than other
      minimally leukotoxic strains. The distribution, clonality, and intrafamilial
      transmission of highly leukotoxic A. actinomycetemcomitans were examined in order
      to determine the importance of leukotoxin in the pathogenesis of periodontitis.
      METHODS: The polymerase chain reaction (PCR) was used to differentiate highly
      leukotoxic from minimally leukotoxic strains in examining 1,023 fresh A.
      actinomycetemcomitans isolates and strains from our culture collection. These
      were obtained from 146 subjects including 71 with localized juvenile
      periodontitis (LJP), 4 with early-onset periodontitis, 11 with post-localized
      juvenile periodontitis, 41 with adult periodontitis, and 19 periodontally normal
      subjects. The arbitrarily primed polymerase chain reaction (AP-PCR) analysis of
      30 oral isolates from each of 25 subjects was used to determine the intraoral
      distribution of A. actinomycetemcomitans clones. AP-PCR was also used to examine
      the transmission of A. actinomycetemcomitans in 30 members of 6 families. The
      clonality of 41 highly leukotoxic A. actinomycetemcomitans strains was evaluated
      by both AP-PCR and ribotyping. RESULTS: Highly leukotoxic A.
      actinomycetemcomitans was found only in subjects with localized juvenile and
      early-onset periodontitis. Fifty-five percent of the LJP subjects harbored highly
      leukotoxic A. actinomycetemcomitans isolates. Seventy-three percent of the A.
      actinomycetemcomitans isolates in these subjects were highly leukotoxic. Highly
      leukotoxic A. actinomycetemcomitans infected younger subjects (mean age 13.95
      years, range 5 to 28 years) than minimally leukotoxic (mean age 35.47 years,
      range 6 to 65 years). Most subjects were infected with only one A.
      actinomycetemcomitans genotype. However, PCR of whole dental plaques and
      subsequent analysis of up to 130 individual oral isolates suggested a possible
      shift in A. actinomycetemcomitans over time in that a few subjects harbored both
      highly leukotoxic and minimally leukotoxic strains. AP-PCR analysis was
      consistent with intrafamilial A. actinomycetemcomitans transmission. Ribotyping
      and AP-PCR analysis confirmed a previous report that highly leukotoxic A.
      actinomycetemcomitans consists of a single clonal type. CONCLUSIONS: This study
      suggests that localized juvenile and other forms of Actinobacillus-associated
      periodontitis are primarily associated with the highly leukotoxic clone of A.
      actinomycetemcomitans.

PMID- 10914796
TI  - Interleukin-8 and granulocyte elastase in gingival crevicular fluid in relation
      to periodontopathogens in untreated adult periodontitis.
AB  - BACKGROUND: This study aimed to determine the relationships among interleukin
      (IL)-8 and granulocyte elastase levels in gingival crevicular fluid (GCF) and the
      concomitant presence of periodontopathogens in untreated adult periodontitis.
      METHODS: GCF and subgingival plaque samples were collected from 16 patients with
      untreated adult periodontitis and 10 healthy control subjects. IL-8 levels were
      determined by enzyme-linked immunosorbent assay (ELISA). Granulocyte elastase was
      analyzed with a neutrophilic granulocyte-specific, low molecular weight and
      chromogenic substrate, L-pyroglutamyl-L-prolyl-L-valine-p-nitroanilide, and the
      maximal rate of elastase activity (MR-EA) was calculated. Five DNA probes were
      used to detect the presence of A. actinomycetemcomitans (A.a.), B. forsythus
      (B.f.), P. gingivalis (P.g.), P. intermedia (P.i.), and T. denticola (T.d.).
      RESULTS: Lower IL-8 concentrations and higher granulocyte elastase activities
      were found in patients than in healthy controls as well as in diseased conditions
      co-infected with B.f., P.g., P.i., and T.d. as compared to healthy conditions
      without the target species (P <0.05). IL-8 concentrations were positively
      correlated with MR-EA levels in the periodontitis conditions co-infected with
      B.f., P.g., P.i., and T.d. (P <0.05). A wide range of IL-8 concentrations was
      found among 15 patients when the periodontitis condition was characterized by co
      infection with B.f., P.g., P.i., and T.d. MR-EA levels in the high IL-8 group of
      subjects were significantly higher than those in the low IL-8 group of subjects
      (P <0.01). CONCLUSIONS: The present study shows that the local host-bacteria
      interactions in untreated periodontitis are diverse in terms of the intensity of
      inflammatory responses measured by IL-8-related granulocyte elastase activity in
      GCF. This might reflect different phases of the inflammatory response due to
      shifts in host-bacteria interactions and therefore be indicative of a range of
      periodontal disease activity levels.

PMID- 10914797
TI  - Prospective study on the augmentation of the maxillary sinus with calcium
      sulfate: histological results.
AB  - BACKGROUND: The main goal of the sinus elevation procedure is the formation of
      vital bone to allow the tissue integration of endosseous implants to support
      prosthetic restorations in the edentulous posterior maxilla. The ideal graft
      material is yet to be found. The present study investigated the histologic
      results of a sinus augmentation procedure performed with calcium sulfate as the
      grafting material. METHODS: The clinical trial consisted of 2 groups: a first
      (control) group of 12 patients (15 sinuses) in which the material was carefully
      placed but not stratified. In the second (test) group, 45 patients (50 sinuses)
      were treated by modifying the application. The calcium sulfate was putty-like in
      consistency and placed as it hardened in layers, avoiding fluid contamination.
      The histologic samples were collected, either at 9 months, at the uncovering
      procedure (for implants placed simultaneously with grafting material), or at 6
      months at the time of implant insertion (for implants placed at a later stage).
      RESULTS: The augmentation procedure resulted in good, new tissue formation within
      the sinuses when clinically and radiographically evaluated. The technique used in
      the test group produced a reduction in the graft shrinkage during healing,
      therefore slowing down the material resorption rate. Histologically, new bone
      formation with progressive lamellar maturation was found in both groups. Some
      particles produced by calcium sulfate resorption were still present after 6
      months in the test group specimens, but no longer detectable after 9 months.
      Samples from the control group showed a mean histomorphometric bone density of
      34.25% +/- 10.02, while samples from the test group showed a mean value of 55.54%
      +/- 19.82. CONCLUSIONS: The results of this study indicate that calcium sulfate
      appears to be an effective material for sinus augmentation, yielding vital bone
      suitable for implant integration. In addition, the technique used in the test
      group seemed to improve the quality and quantity of bone formation.

PMID- 10914798
TI  - Occurrence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and
      Prevotella intermedia in progressive adult periodontitis.
AB  - BACKGROUND: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and
      Prevotella intermedia are the major periodontal bacteria species in most forms of
      progressive periodontitis in Scandinavia and the United States. The occurrence of
      periodontal pathogens appears to be different in subjects of different ethnic
      origin, and geographical factors may influence the distribution of these species.
      METHODS: The occurrence of A. actinomycetemcomitans, P. gingivalis, and P.
      intermedia was determined using a DNA probe in progressive adult periodontitis in
      Chileans. Sixty patients (mean age 43.6 +/- 8 years) who had not previously
      received any type of periodontal therapy were selected. Bleeding on probing,
      probing depth, and clinical attachment level measurements were made with an
      automated probe. Patients were monitored at 2-month intervals until at least 2
      sites exhibited > or =2 mm attachment loss. Two subgingival plaque samples from
      active sites were taken in 56 subjects and matched with 2 plaque samples from
      inactive sites in the same individuals. RESULTS: P. gingivalis was found in 75%
      of active sites and in 59.7% of inactive sites in 96% of the patients (P =
      0.022). P. gingivalis at high levels of detection was significantly more frequent
      in active sites (48.2%) than in inactive sites (31.2%) (P = 0.014). A.
      actinomycetemcomitans was detected in 6.25% of active sites and in 12.5% of
      inactive sites in 11.6% of patients. P. intermedia was found in 33% of patients
      and at a significantly higher proportion in active sites (49.1%) than in inactive
      sites (30.3%) (P = 0.006). There was a significantly higher proportion of
      inactive sites (34.8%) than active sites (19.6%) without any of the 3 pathogens
      (P = 0.016). Bleeding on probing was significantly more associated with active
      sites with high levels of P. gingivalis and with active sites with P. intermedia
      than with inactive sites. CONCLUSIONS: A high prevalence of P. gingivalis and P.
      intermedia was found in adult periodontitis, and the occurrence of these bacteria
      appears to be higher in Chileans than in other populations. No apparent
      association exists between A. actinomycetemcomitans and progressive adult
      periodontitis in Chileans.

PMID- 10914800
TI  - Ultrastructural and immunoelectron microscopic studies of the peri-implant
      epithelium-implant (Ti-6Al-4V) interface of rat maxilla.
AB  - BACKGROUND: The role played by the internal basal lamina (IBL) and hemidesmosomes
      between an implant and the peri-implant epithelium (PIE) in the adherence of the
      epithelium to the implant is controversial. This study used rat maxilla
      implantation models to clarify the ultrastructure of the PIE-implant interface.
      METHODS: Ti-6Al-4V implants were inserted either immediately or 2 weeks after the
      extraction of the upper left first molar of 6- or 4-week-old rats, respectively.
      The junctional epithelium (JE) of the upper right molars in the same animals was
      used as a control. Four weeks after implantation, the animals were sacrificed to
      prepare specimens for light and immunoelectron microscopy. RESULTS: Under light
      microscopy, the PIE appeared to attach to the implant surface. Ultrastructurally,
      IBL, consisting of the lamina densa and lamina lucida, and hemidesmosomes were
      formed only in the lower region, and rarely in the middle region, of the PIE
      implant interface. In control teeth, the IBL and hemidesmosomes formed throughout
      the dento-JE interface. Laminin-1 was found in the IBL and also in the vesicles
      and vacuoles of the PIE and JE cells. Statistical analysis showed that there was
      also a significant difference in the amount of IBL between the PIE-implant and
      dento-JE interfaces. CONCLUSIONS: PIE attached to the implant via hemidesmosomes
      and IBL in the lower region of the PIE-implant interface. Although PIE cells may
      secrete laminin-1, which contributes to epidermal cell adhesion, the PIE which
      attaches to implants only in the lower region of the interface is considered to
      be the poorly adhered epithelium.

PMID- 10914799
TI  - Phenytoin and cyclosporin A suppress the expression of MMP-1, TIMP-1, and
      cathepsin L, but not cathepsin B in cultured gingival fibroblasts.
AB  - BACKGROUND: Fibroblasts are known not only to synthesize and secrete
      extracellular matrix proteins, but also to degrade them for connective tissue
      remodeling. Drug-induced gingival overgrowth is characterized by a massive
      accumulation of extracellular matrix components in gingival connective tissues.
      Although some previous reports suggested that causative drugs stimulated the
      fibroblast proliferation, the results are not conclusive yet. In this study, we
      hypothesized that drug-induced gingival overgrowth could be a consequence of
      impaired ability of matrix degradation rather than an enhanced proliferation of
      gingival fibroblasts induced by these drugs. METHODS: Normal human gingival
      fibroblasts were cultured with or without either 20 microg/ml of phenytoin or 200
      ng/ml of cyclosporin A. Total RNA and cellular proteins were collected every day
      for RT-PCR analyses and for measuring lysosomal enzyme activity. In addition, an
      immunohistochemical study was performed to detect lysosomal enzymes in cells from
      enlarged gingiva of the patients with phenytoin-induced gingival overgrowth.
      RESULTS: RT-PCR analyses revealed that these drugs suppressed the expression of
      MMP-1, TIMP-1, and cathepsin L, but not that of cathepsin B in a time-dependent
      manner. Then, we measured the activity of lysosomal enzymes and cathepsin B and
      L. The results indicated that although cathepsin B activity was not observed to
      be impaired, regardless of the drugs used in these cells, both total and active
      forms of combined activity of cathepsins B and L were suppressed in a time
      dependent manner. CONCLUSIONS: The results indicate that, besides suggested
      effects of these drugs on gingival fibroblasts and/or on accumulated cells in the
      gingival tissues, extracellular matrix-degrading ability, particularly that by
      cathepsin L, is also suppressed by cyclosporin A and phenytoin in gingival
      fibroblasts, and that lysosomal enzyme plays an important role in the
      pathogenesis of drug-induced gingival hyperplasia.

PMID- 10914801
TI  - Inverse dose- and time-dependent effect of basic fibroblast growth factor on the
      gene expression of collagen type I and matrix metalloproteinase-1 by periodontal
      ligament cells in culture.
AB  - BACKGROUND: Growth factors are known to play a major role in the regeneration of
      the periodontium. Basic fibroblast growth factor (bFGF) is a polypeptide growth
      factor considered to have a role in chemotaxis and mitogenesis of periodontal
      ligament cells (PLC). The aim of this study was to assess the dose-dependent
      effect of bFGF administration on the levels of gene expression of collagen type I
      (a1) (col I), collagen type III (col III), and collagenase-1 (MMP-1) in PLC.
      METHODS: PLC were cultured in different concentrations of bFGF (0.1 to 10 ng of
      bFGF) for 14 and 21 days. At each time point, the gene expression of the examined
      molecules was assessed semi-quantitatively by reverse transcription-polymerase
      chain reaction (RT-PCR) assay. RESULTS: The results indicated that bFGF exhibits
      an inverse time- and dose-dependent effect on the gene expression of col I and
      MMP-1: it simultaneously downregulates the gene expression of col I and
      upregulates the gene expression of MMP-1. On the other hand, bFGF had no dose
      dependent effect on col III gene expression. The effect of bFGF on the expression
      of the three genes was modulated by the time of incubation with bFGF.
      CONCLUSIONS: These results suggest that bFGF is one of the important regulators
      involved in the active remodeling of col I in the periodontal ligament and
      possibly in other connective tissues.

PMID- 10914802
TI  - Human herpesviruses and Porphyromonas gingivalis are associated with juvenile
      periodontitis.
AB  - BACKGROUND: Although herpesviruses have been associated with adult periodontitis,
      their relationship with juvenile periodontitis (JP) has not been established.
      This case-control study examined possible associations between JP and pathogenic
      bacteria, the human cytomegalovirus (HCMV), and the Epstein-Barr type 1 virus
      (EBV-1). METHODS: Subjects were participants in a larger survey of schoolchildren
      in North-Central Jamaica. Subgingival plaque samples from 15 subjects with JP, 20
      with incipient periodontitis (IP), and 65 randomly-selected healthy controls were
      assayed for Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans
      using a 16S rRNA polymerase chain reaction (PCR) identification method, and for
      HCMV and EBV-1 using nested PCR identification. RESULTS: Strong bivariate
      associations were found between JP and P. gingivalis (odds ratio [OR] = 12.7; 95%
      CI = 2.6, 61.4), HCMV (OR = 10.0; 95% CI = 2.7, 36.3), and A.
      actinomycetemcomitans (OR = 8.0; 95% CI = 2.3, 27.5), but not EBV-1. In
      multivariate analyses, P. gingivalis remained a significant explanatory variable
      (OR = 7.8; 95% CI = 1.5, 40.9); however, the associations were marginal for HCMV
      (OR = 4.6; 95% CI = 0.9, 22.7), and non-significant for A. actinomycetemcomitans
      (OR = 2.0; 95% CI = 0.4, 9.7). The associations with JP and the extent of
      attachment loss were even stronger when both P. gingivalis and HCMV were detected
      together. P. gingivalis (OR = 3.9; 95% CI = 1.3, 12.0) and EBV-1 (OR = 3.3; 95%
      CI = 1.0, 10.3) were the only significant explanatory variables in the
      multivariate analysis of IP. CONCLUSIONS: P. gingivalis is the strongest and most
      stable indicator of periodontitis in Jamaican adolescents. Co-infection with P.
      gingivalis and HCMV appears to be particularly deleterious to periodontal health.

PMID- 10914803
TI  - Coronally positioned flap procedures with or without a bioabsorbable membrane in
      the treatment of human gingival recession.
AB  - BACKGROUND: A variety of surgical techniques have been used to cover recession
      type defects. New data have indicated that the outcome of coronally positioned
      flap procedures may be augmented by supporting the flap with a membrane. METHODS:
      The present study aimed at comparing the clinical outcome following treatment of
      localized gingival recessions by a coronally positioned flap procedure alone, or
      combined with a bioabsorbable membrane. Twenty patients with buccal bilateral
      Miller Class I or Class II gingival recessions in cuspids or premolars
      participated in the study. The split-mouth design, randomized selection of site
      treatment, and blind evaluation provided 20 sites in a membrane group and 20
      sites in a non-membrane group for examination at baseline, and at 3 months and 6
      months postoperatively. Clinical variables included the apical extent of the
      gingival recession, the width of the recession defect measured at the cemento
      enamel junction (CEJ), and the width of keratinized tissue at the recession site
      as well as probing depth and attachment level. RESULTS: Both treatments resulted
      in a significant gain (P <0.0001) of root coverage, amounting to an average of
      2.3 mm in the membrane group and 2.5 mm in the non-membrane group at the 6-month
      evaluation. There was no significant difference between the treatments.
      Similarly, a significant gain of clinical attachment level was seen in the
      membrane (1.3 mm; P <0.001) as well as in the non-membrane (1.5 mm; P <0.0001)
      group, but without a significant difference between the groups. The reduction of
      the recession width from baseline to 6 months was significantly greater (P <0.01)
      for the non-membrane (2.3 mm) than for the membrane (1.4 mm) group. Probing depth
      changes were small and not significant for either of the treatments. When
      patients were grouped as smokers (8) and non-smokers (12), no significant
      differences were revealed for any of the response variables. Overall, among the
      20 membrane sites, one showed no change while the remaining 19 gained root
      coverage at the 6-month examination. Five sites obtained coverage to the CEJ.
      Among the non-membrane sites, all gained root coverage at 6 months and 10 sites
      showed complete coverage to the CEJ. CONCLUSIONS: The coronally positioned flap
      operation offers a predictable, simple, and convenient approach as a root
      coverage procedure in Miller Class I and Class II recession defects. Combining
      this technique with the placement of a bioabsorbable membrane does not seem to
      improve the results following surgical treatment of such defects.

PMID- 10914804
TI  - Guided tissue regeneration with bioabsorbable barriers: intrabony defects and
      class II furcations.
AB  - BACKGROUND: The aim of this study was to compare the effects of guided tissue
      regeneration (GTR) using 2 different bioabsorbable barriers (control: polylactide
      acetyltributyl citrate; test: polydioxanon). The polydioxanon barrier is an
      experimental membrane for GTR therapy that consists of a continuous occlusive
      barrier that has a layer of slings on the side that is meant to face the
      mucoperiosteal flap. METHODS: In 21 patients with 22 pairs of similar
      contralateral defects (30 intrabony and 14 Class II furcation lesions), each
      defect was randomly assigned for treatment with either control (c) or test (t)
      devices. At baseline and 12 months after surgery, clinical measurements, plaque
      index (PI) gingival index (GI), probing depth (PD), and vertical and horizontal
      clinical attachment loss (CAL-V; CAL-H) and standardized radiographs were
      obtained. RESULTS: Barrier exposure was commonly observed in both groups. Four
      weeks after surgery 61% of all barriers were exposed to some extent. However,
      both treatments revealed a significant GI reduction (P <0.005), PD reduction (
      3.08 +/- 2.29 mm [t]; -3.52 +/- 2.67 mm [c]; P <0.001) and CAL-V gain (2.44 +/-
      2.29 mm [t], 2.80 mm +/- 2.21 [c]; P <0.001) 12 months after surgery in all
      defects. Within the intrabony defects significant bony fill (2.03 +/- 1.70 mm
      [t]; 1.91 +/- 1.20 mm [c]; P = 0.001), and within the furcations a significant
      but small CAL-H gain (0.79 +/- 0.68 mm [t]; 1.13 +/- 1.44 mm [c]; P <0.05), was
      observed. CONCLUSIONS: Regarding GI and PD reduction as well as CAL-V and CAL-H
      gain, this study failed to reveal statistically significant or clinically
      relevant differences between test and control 12 months postsurgically. Thus, the
      use of both bioabsorbable barriers in GTR therapy may be recommended.

PMID- 10914805
TI  - Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental
      periodontitis in rats.
AB  - BACKGROUND: Prostaglandins are implicated in periodontal bone destruction. We
      investigated the effect of a non-selective cyclooxygenase (COX) inhibitor
      (indomethacin-IND) or a type 2 COX inhibitor (meloxicam-MLX) in an experimental
      periodontal disease (EPD) model. METHODS: Wistar rats were subjected to placement
      of a nylon thread ligature around the maxillary molars and sacrificed after 7
      days. Alveolar bone loss (ABL) was measured in one quadrant as the distance
      between the cemento-enamel junction and the alveolar bone. The other quadrant was
      processed for histopathologic analysis. Daily weight and white blood cell count
      were recorded. Groups were treated subcutaneously for 7 days with either IND
      (0.5, 1, or 2 mg/kg) or MLX (0.75, 1.5, or 3 mg/kg). Controls received no
      treatment. Macroscopic analysis of the gastric mucosa was done. The control group
      did not receive any manipulation, and a non-treated group consisted of rats
      subjected to periodontitis that received no pharmacological treatment. RESULTS:
      In the non-treated (NT) group, there was significant ABL, severe mononuclear
      influx, and an increase in osteoclast numbers. Significant neutrophilia and
      lymphomonocytosis occurred at 6 hours and at 7 days, respectively, as compared to
      controls. Significant weight loss persisted until the seventh day in the NT
      group. Both IND and MLX reduced ABL and histopathologic changes. Neutrophilia and
      lymphomonocytosis were also significantly reversed. Both IND and MLX induced
      earlier weight recovery. The stomachs of the IND (1 and 2 mg/kg) groups presented
      hemorrhage and ulcers, whereas in the MLX-treated groups, there were mild
      petechiae just in the 3 mg/kg group. CONCLUSIONS: COX inhibition prevented ABL in
      this experimental periodontal disease model. MLX displays similar efficacy and
      less gastric damage than IND. MLX may provide a better risk/benefit ratio in the
      treatment of human periodontitis than non-selective COX inhibitors.

PMID- 10914806
TI  - Porous bovine bone mineral in healing of human extraction sockets. Part 1:
      histomorphometric evaluations at 9 months.
AB  - BACKGROUND: Extraction socket wound healing is characterized by resorption of the
      alveolar bone at the extraction site. This produces a decrease in ridge volume,
      deformations of ridge contours, and, thus, difficulties in delayed placement of
      root-form implants in an ideal position. Cancellous porous bovine bone mineral
      (PBBM) applied to fresh extraction sockets has recently been proposed to minimize
      the reduction in ridge volume. The aim of this study was to investigate the
      influence of PBBM grafted particles on the histopathologic pattern of the
      intrasocket regenerated bone and to evaluate histomorphometrically the healed
      PBBM grafted extraction socket site at 9 months' post-extraction. METHODS: PBBM
      particles (250 to 1,000 microns in size) were grafted in 15 fresh human
      extraction sockets in 15 patients. Socket wall bone height was measured from the
      crestal ridge level before the mineral particles were inserted. Primary soft
      tissue closure was performed to protect the grafted particles via a pediculated
      split palatal flap. At 9 months, socket bone walls were remeasured and cylinder
      bone samples of the previously PBBM-grafted sites were obtained. Decalcified
      specimens were sectioned at a cross-horizontal plane and stained with hematoxylin
      and eosin for histopathologic and histomorphologic examination. Tissue area
      percentage of bone, PBBM, and connective tissue (CT) was calculated for each
      specimen from the crestal to the apical region and changes in values compared.
      RESULTS: Average clinical overall bone fill of the augmented socket sites was
      82.3%. Histologically, PBBM particles were observed in all specimens. Newly
      formed bone was characterized by abundance of cellular woven-type bone in the
      coronal area, while lamellar arrangements could be identified only in the more
      apical region. New osseous tissue adhered to the PBBM. Histomorphometric
      measurements showed an increase of mean bone tissue area along the histological
      sections from 15.9% in the coronal part to 63.9% apically (average 46.3%). CT
      fraction decreased from 52.4% to 9.5% (average 22.9%) from the crestal to the
      apical region. PBBM area fraction varied from 26.4% to 35.1% (average 30.8%).
      Statistical analysis of the comparison between areas of bone, CT, and PBBM was
      performed in different points along the coronal-apical axis. Differences were
      significant (P <0.01) at the most crestal, middle, and apical section cut areas,
      but not at the cervical section cuts. Bone area fraction increased in the apical
      direction as much as CT correlatively decreased. Unlike CT and bone, PBBM
      retained constant relative volume (approximately 30%), regardless of the depth of
      the specimen cores. CONCLUSIONS: PBBM particles are an appropriate biocompatible
      bone derivative in fresh extraction sockets for ridge preservation. The
      resorbability of this xenograft could not be recognized in a 9-month period.
      Further investigation is needed to clarify the resorptive mechanisms of PBBM.

PMID- 10914807
TI  - Long-term follow-up of periodontitis in a patient with Chediak-Higashi syndrome.
      A case report.
AB  - Chediak-Higashi syndrome (CHS) is an extremely rare hereditary disease
      characterized by leukocyte dysfunction. We report on a 21-year-old woman who
      presented at the age 9 years with CHS and serious periodontal tissue destruction
      around erupted teeth. The patient had received systemic, radiographic,
      immunological, microbial, and clinical periodontal examinations since childhood.
      The chemotactic activity of neutrophils in the Boyden chamber assay was 22% of
      the control, and leukocyte bactericidal activity was one-third of the control.
      Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Prevotella
      intermedia were isolated from periodontal pockets. Periodontal treatment
      including oral hygiene was provided, followed by professional tooth cleaning from
      the age of 12 to 21 years. However, the mobility of teeth and the inflammation of
      periodontal tissue progressed. This CHS patient presented with periodontal
      disease of extremely early onset, which was resistant to periodontal treatment.

PMID- 10914808
TI  - Self-inflicted gingival injury due to habitual fingernail biting.
AB  - Self-inflicted gingival injuries have been known to occur in children and
      adolescents secondary to a number of causes, including accidental trauma;
      fingernail biting; digit sucking; or sucking on objects such as pens, pencils,
      thread, or toothpicks. Of these causes, the one documented as the most common
      cause is habitual fingernail biting or onychophagia. This case report describes
      the gingival injury caused by habitual fingernail biting and the findings noted
      at the time of periodontal surgery. The potential ramifications of fingernail
      biting are discussed, and the steps necessary to ensure and preserve the dental
      health of the patient are identified.

PMID- 10914809
TI  - Buccal alveolar exostoses: prevalence, characteristics, and evidence for
      buttressing bone formation.
AB  - BACKGROUND: Buttressing bone formation has been described as the development of
      thickened or exostotic buccal alveolar bone in response to heavy occlusal forces.
      Little supporting evidence for this model has been found in previous literature,
      however, and there is little seen on the prevalence or characteristics of buccal
      alveolar exostoses. METHODS: A sample of 416 selected teeth and investing bone in
      52 modern skeletal specimens at the National Museum of Natural History were
      examined. Two measures of heavy occlusal function--periodontal ligament (PDL)
      width and occlusal attrition--were analyzed for their relationship to three
      parameters of buccal alveolar bone (exostoses, lipping, and overall thickness).
      RESULTS: Buccal alveolar bone enlargements were found in 25% of all teeth
      examined: 18% were expressed as marginal bony lippings and 7% as buccal
      exostoses. Exostoses were mainly seen around maxillary molars and bicuspids,
      especially in males, while lippings were seen in molars, bicuspids, and
      mandibular incisors, with even gender distribution. When findings were controlled
      for arch and tooth type, no significant correlations were found between wider PDL
      spaces or occlusal attrition and exostotic, lipped, or thicker alveolar bone.
      CONCLUSIONS: These results indicate a lack of anatomic evidence for the theory of
      buttressing bone formation and suggest that other factors may be of greater
      importance in the etiology of buccal bone enlargements. Incidentally, no
      correlation was found between widened PDL spaces or severe occlusal attrition and
      the presence of cervical loss of tooth structure, which casts doubt on the
      currently popular concept of abfraction.

PMID- 10914810
TI  - Retention of multi-rooted teeth with class III furcation lesions utilizing
      resins. Report of 17 cases.
AB  - BACKGROUND: Treatment of periodontally diseased multi-rooted posterior teeth has
      conventionally consisted of scaling and root planing, apically positioned flaps,
      tunneling, root amputation, root resection, guided tissue regeneration, osseous
      grafting, and combination osseous graft and barrier membrane techniques.
      Successful treatment has often been directed and measured by how well the
      clinician obtains sufficient access to facilitate patient hygiene efforts. Long
      term success is predicated upon tooth retention and the arrest of further
      destruction within the furcation area. METHODS: Seventeen adult periodontal
      patients with Class III furcation defects were evaluated. Using an open flap
      procedure, a resin-ionomer was placed into all 3 furcation defects. The patients
      were placed on quarterly maintenance appointments and the teeth evaluated up to 1
      year. RESULTS: The results revealed that sealing the furcations of multi-rooted
      teeth with hopeless prognoses seems to be a viable alternative to accessing the
      same intraradicular areas for maintenance using more conventional modes of
      therapy. Sealing further decreases the surface area of the furca and simplifies
      future maintenance. CONCLUSIONS: The present study showed that teeth with
      hopeless prognoses might be retained by decreasing probing depths, bleeding upon
      probing, and mobility when furcation areas are sealed with a resin-ionomer.

PMID- 10914811
TI  - When not to perform root coverage procedures.

PMID- 10914812
TI  - Re: A comparison of endosseous dental implant surfaces. Cochran DL (1999;70:1523
      1539).

PMID- 10914813
TI  - Re: A comparison of endosseous dental implant surfaces. Cochran DL (1999;70:1523
      1539).

PMID- 10914814
TI  - Re: A comparison of endosseous dental implant surfaces. Cochran DL (1999;70:1523
      1539).

PMID- 10914815
TI  - Micrometastatic nodal disease in breast cancer--the dilemma continues.

PMID- 10914816
TI  - Expression and significance of urokinase type plasminogen activator gene in human
      brain gliomas.
AB  - BACKGROUND AND OBJECTIVES: Urokinase type plasminogen activator (uPA) regulates a
      variety of processes involved in tissue morphogenesis, cell differentiation,
      migration and invasion. We analyzed the available informations to better
      interpret the pathogenetic relationship between uPA activity and the malignant
      biological behavior of human brain gliomas. METHODS: We retrospectively studied
      the presence and distribution of uPA in human brain gliomas by Northern blot
      hybridization and immunohistochemical methods in 43 cases of brain gliomas and 5
      cases of normal brain tissues. RESULTS: All tissues expressed 2.5 kb transcripts
      of uPA mRNA. The uPA mRNA levels were significantly higher in high-grade gliomas
      than in low-grade gliomas and normal brain tissues (P < 0.01). Levels of uPA mRNA
      expression in tumor tissues with recurrence in 18 months postoperatively and
      survival period less than 3 years were significantly higher than counterparts (P
      < 0.01). The distribution of uPA protein in the immunoreactivity was mainly in
      tumor cells and microvascular endothelial cells of glioblastomas and anaplastic
      astrocytomas, localizing at cytoplasms, especially near sites of vascular
      proliferation and at the leading edges of tumors. CONCLUSIONS: High expression of
      uPA gene is associated with the malignant progression of gliomas and demonstrates
      a high level of correlation with the recurrence and invasive behaviors of high
      grade gliomas.

PMID- 10914817
TI  - Challenging the myth of exercise-induced lymphedema following breast cancer: a
      series of case reports.
AB  - Women who have had axillary lymph nodes removed for the management of breast
      cancer are at increased risk of developing upper extremity lymphedema. Physical
      therapists, surgeons, and other health professionals have warned these women to
      avoid vigorous, repetitive, or excessive upper body exercise, believing that such
      types of exercise might actually induce lymphedema. The purpose of this series of
      case reports was to challenge that belief by systematically measuring the arm
      circumferences, across three points in time, of 20 women who had received
      axillary dissection and who were competing in the vigorous, upper body sport of
      Dragon Boat racing. Measurably different change was defined as an increase in
      circumference of the ipsilateral upper extremity at any of the four landmarks of
      >0.5 inches between Time 1 and Time 2 or between Time 1 and Time 3; only two
      women showed a measurably different change (5/8 in). Furthermore, none of the
      women showed a clinically significant difference in arm circumference between the
      ipsilateral and contralateral extremities at Time 3.

PMID- 10914818
TI  - Microsatellite alterations on human chromosome 11 in in situ and invasive breast
      cancer: a microdissection microsatellite analysis and correlation with p53, ER
      (estrogen receptor), and PR (progesterone receptor) protein immunoreactivity.
AB  - BACKGROUND AND OBJECTIVES: Microsatellite instability (MSI) has been documented
      in a subset of sporadic tumors. Loss of heterozygosity (LOH) on chromosome 11
      loci in breast cancer is a frequent event. The purpose of the present study is to
      examine the incidence of microsatellite alterations in in situ and invasive human
      breast carcinoma and to clarify their significance in regulating the dynamics of
      cancer progression. METHODS: Four highly polymorphic (CA)n repeat microsatellites
      were used to determine microsatellite alterations in ten ductal carcinoma in situ
      (DCIS) and 19 invasive ductal carcinoma (IDC). To investigate the expression of
      p53, ER (estrogen receptor), and PR (progesterone receptor) association with MSI,
      immunohistochemistry staining was applied. RESULTS: MSI were detected in 20%
      (2/10) of DCIS and in 47.4% (9/19) of IDC. The frequency of MSI in IDC was
      significantly higher than that in DCIS (P < 0.001). Also, the MSI seemed to
      correlate with clinical stage (P = 0.0001) and tumor size (P = 0.004) but not
      histological grade or age. In addition, we found that 27% of the tumors showed
      LOH at 11q23.3-24 region between loci D11S934 and D11S912. Seven of nine MSI
      cases demonstrated low or no expression of p53. However, there was significantly
      reduced expression of PR, but not ER in MSI cases. CONCLUSIONS: Our results
      suggest that breast cancer acquires the RER phenotype (replication-error
      phenotype) in the relatively late stages, and that the RER phenotype is
      associated with aggressiveness of IDC (infiltrative duct carcinoma). The result
      also implicated that mismatch repair failure can alter the expression of PR but
      not ER and p53.

PMID- 10914819
TI  - Results of conservative surgery for limited-sized infiltrating breast cancer:
      analysis of 962 tested patients: 24 years of experience.
AB  - BACKGROUND AND OBJECTIVES: Breast-conserving treatment (BCT) is the elective
      approach to early stage breast cancer. We report on our 24 years of experience.
      METHODS: Between 1975 and 1998, 980 conservative surgical procedures in 962
      patients for limited-sized infiltrating breast cancer (T1 to "small" T2, N0-N1,
      M0) were performed. BCT consisted of a local wide excision, axillary dissection
      and postoperative radiation therapy to the entire breast (50 Gy). An adjuvant
      systemic treatment (chemo- and/or hormonotherapy) was administered to the large
      majority of patients. Data on age, menopausal status, histologic subtype of
      tumor, quadrant site of cancer, tumor size (Tla, T1b, T1c, or T2), axillary nodal
      status (N- or N+, with involvement of 1-3 nodes, or more), and follow-up were
      stored for each patient. Overall, N+ patients constituted 29.2% of the total
      number. Survival data were analyzed using the Berkson-Gage actuarial method.
      RESULTS: The 15-year overall and disease-free survival rates were 72% and 67%,
      respectively. Nevertheless, the more interesting results concern survival rates
      in relation to T and N parameters. T-related survival showed a sharp distinction
      among the subgroups T1a + T1b and T1c, with values of 90% for the former versus
      62% for the latter. Even more significative results were achieved by comparing N
      with survival. In fact, it was 84% for N-patients and 31% for N+ patients; for N+
      patients, outcome was poor for the subgroup showing an involvement of more than 3
      nodes, with no patient surviving at 15 years. None of the other evaluated
      parameters proved to be related to survival. The validity of our protocol is
      confirmed by the low number of local relapses: only 33 (3.4%) of 980 total
      treated cases. Cosmetic results were excellent or good in a high percentage of
      patients (>80%). CONCLUSIONS: These results unquestionably confirm the validity
      of BCT, provided certain prerequisites are fulfilled.

PMID- 10914820
TI  - Fractal heterogeneity of peripheral blood flow: implications for hematogenous
      metastases.
AB  - BACKGROUND AND OBJECTIVES: To determine how inhomogeneities in blood perfusion
      might affect the number of metastases that develop within an individual with
      cancer. METHODS: Experiments with lung metastases in mice, involving 320
      treatment groups and 3165 mice, were reviewed. Inhomogeneities in the
      distribution of metastases amongst identically treated mice were analyzed by
      calculating the relative dispersion and clumping index. RESULTS: The relative
      dispersion exhibited fractal self-similarity on change of scale, and paralleled
      the effects observed with pulmonary blood flow. Clustering of metastases was also
      apparent: a minority of mice developed relatively large numbers of metastases; a
      majority of mice developed few metastases. CONCLUSIONS: Clustering of lung
      metastases occurred within groups of identically treated mice, and could be
      attributed to inhomogeneous blood perfusion. Consequently, the number of
      metastases in any individual was highly variable and correlated only partly with
      malignant potential. Inhomogeneities in blood flow favored the development of
      relatively few metastases, such that solitary or nil metastasis should occur more
      frequently than expected from chance alone.

PMID- 10914821
TI  - A physical-based model for the simulation of neoplastic growth and metastasis.
AB  - BACKGROUND AND OBJECTIVES: It is possible to formulate models capable of
      reproducing the main details of the physical processes involved in the evolution
      of biological systems. The complexity of the problem requires to begin with a
      simple and universal model for the description of the cellular growth, to be
      adapted successively to the local conditions found in clinically observed
      neoplastic growths. METHODS: A model based on the Local Interaction Simulation
      Approach (LISA) has been formulated for the simulation of growth, diffusion, and
      metastasis of neoplasms. The vascularization is described by a blood vessel
      located on one edge of the specimen in which a constant and homogeneous flow is
      assumed. A nutrient density is defined to mimic the blood flow within the tissue.
      RESULTS: Photograms taken at proper times may identify the main characteristics
      of the tumor evolution and describe its volume variations in a transversal
      section. Furthermore, it is possible to monitor constantly the volume of the
      neoplasm and of the necrotic tissue as a function of time, as well as the portion
      of cells that have migrated in the blood vessel. CONCLUSIONS: In spite of strong
      simplifying assumptions, the model presents good qualitative agreement with
      clinical data, which may be further improved by more detailed information about
      cancer cells properties or local vascular system patterns.

PMID- 10914822
TI  - Problems in reconstructive surgery in the treatment of carcinoma of the
      hypopharyngoesophageal junction.
AB  - BACKGROUND AND OBJECTIVES: Thirty percent of carcinomas of the pyriform sinus
      manifest generally with infiltrations in the cervical esophagus. In recent years,
      progress in reconstructive surgery has broadened surgical indications to include
      tumors previously managed with palliative measures alone. In some cases, radical
      surgery has been extended to creating safer resection margins, with more and more
      indications for circular pharyngectomy. Lesions involving the
      hypopharyngoesophageal junction pose particular problems; furthermore, the high
      rate of synchronous or metachronous tumors warrants the indication for total
      esophagectomy, which requires complex reconstructive techniques. METHODS: We
      report on a series of 21 patients who underwent pharyngocoloplasties after
      receiving total pharyngolaryngoesophagectomy. RESULTS: With regard to the
      oncologic results, after a follow-up of 2-60 months, 9 patients had no evidence
      of disease, 5 patients died during the postoperative course, 2 patients survived
      with disease, 4 died with disease, 1 died from metachronous breast carcinoma, and
      7 underwent reintervention. CONCLUSIONS: In cases in which reconstruction by
      gastric pull-up is considered risky, if not contraindicated, pharyngocoloplasty
      represents a particularly reliable treatment option. The limits and advantages of
      the technique are discussed. The procedure permitted us to reconstruct the
      digestive tract, without encountering problems any more serious than those a
      normal gastric pull-up procedure would pose.

PMID- 10914823
TI  - Feasibility of daily concurrent chemoradiation therapy as nonsurgical management
      for esophageal cancer: our experience and theoretical background.
AB  - BACKGROUND AND OBJECTIVES: Many combination patterns of chemotherapy and
      radiotherapy (chemoradiation therapy; CRT) for the treatment of esophageal cancer
      indicate that the optimal doses of chemotherapeutic agents and of chemotherapy
      and radiotherapy regimens remain unclear. The feasibility and promising outcome
      of our newly developed definitive CRT for nonsurgical management of esophageal
      cancer, essentially based on the theoretical backgrounds of the radiosensitizing
      and biochemical modulation effects of chemotherapeutic agents, is investigated.
      METHODS: Six nonoperated esophageal cancer patients were treated by daily
      concurrent CRT, which consisted of continuous 5-fluorouracil administration with
      leucovorin, combined with a low dose of daily cisplatin administration before
      each fraction of radiation. Response to CRT and toxicities and survivals were
      evaluated. RESULTS: Complete and partial responses were seen in 2 patients each.
      Histologic examination of the biopsy specimens in the primary site showed no
      cancer cells in 4 patients; 1 of them survived for 31 months after CRT. The other
      2 patients showed good-quality survival, having dramatic relief from dysphagia.
      There were no treatment-related deaths. CONCLUSIONS: The daily concurrent CRT is
      rational and promising and compares well with other series of definitive CRT. The
      CRT based on the theoretical background is feasible as a nonsurgical management
      option for esophageal cancer patients.

PMID- 10914824
TI  - Treatment-related acute gastric bleeding managed successfully with surgical
      devascularization.
AB  - BACKGROUND AND OBJECTIVES: Patients with gastric lymphoma treated by chemotherapy
      or radiation therapy are at high risk of developing complications, most commonly
      perforation or bleeding. In any case of upper gastrointestinal tract bleeding
      during conservative treatment for gastric lymphoma, thorough investigation is
      required to exclude other causes of hemorrhage which could be managed
      appropriately. When the source of bleeding is the tumor, the only effective
      measure is resection of the stomach, a very dangerous operation in these poor
      risk patients. METHODS: We treated 3 consecutive patients with life-threatening
      gastric bleeding from lymphoma treated by chemotherapy. RESULTS: We successfully
      controlled the hemorrhage by surgical devascularization. CONCLUSION:
      Devascularization of the involved part of the stomach is safe and effective.

PMID- 10914826
TI  - Cystic liver metastases from colorectal cancer.
AB  - BACKGROUND AND OBJECTIVES: Cystic liver metastases from colorectal cancer are
      rarely reported. METHODS: Clinicopathological and radiological analyses were
      performed on six cases of cystic liver metastases from colorectal cancer.
      RESULTS: Computed tomography or ultrasound findings for the tumors were atypical
      for metastases of colorectal cancer, and the lesions needed to be differentiated
      from cystadenocarcinoma and benign tumors. The histological findings were
      peculiar: the central portions of the tumors contained necrotic tissue or areas
      of hemorrhage, and adenocarcinoma cells were found predominantly outside well
      developed fibrous capsules. CONCLUSIONS: Clinicopathological observations
      suggested that these metastatic tumors had the potential to grow rapidly, but,
      unexpectedly, the patients had favorable prognoses.

PMID- 10914825
TI  - A feasibility study of chemosensitivity assay by adhesive tumor cell culture
      system using biopsy specimens for gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: The adhesive tumor cell culture system (ATCCS) is
      known to produce high colony-forming efficiency. We, therefore, studied the
      feasibility of ATCCS for gastric cancer by use of biopsy specimens and the
      relationship between the results of ATCCS and histological effects of anticancer
      drugs. METHODS: Tumor specimens extracted by gastroendoscopic biopsy were
      sufficient for obtaining the result of sensitivity to at least one drug in 24 out
      of 30 (80%) patients. Twenty patients were administered 5-fluorouracil (5-FU) for
      14 days prior to surgery, and the results of ATCCS were compared with
      histological changes of the resected specimens. RESULTS: The histological
      response rate was found to be 100% (4/4) when the 90% inhibition concentration
      (IC90) of 5-FU was less than 0.24 microg/ml (sensitive) and was 0% (0/3) when
      IC90 was greater than 0.40 microg/ml (resistant). CONCLUSIONS: Although lacking
      in statistical significance, the results suggest that the drug to which the tumor
      revealed sensitivity in the ATCCS would produce histological effects and the drug
      to which the tumor was resistant would have no histological effect.

PMID- 10914827
TI  - Influence of the surgical treatment on local recurrence of rectal cancer: a
      prospective study (1980-1992).
AB  - BACKGROUND AND OBJECTIVES: The incidence of locoregional recurrences (LR)
      following radical surgery of rectal cancer varies from 5% to 30% according to the
      literature. The purpose of this prospective study was to compare the outcome of
      the Abdomino-Perineal Excision (APE) vs. the Anterior Resection (AR) in a
      consecutive series of 188 patients who underwent surgery for cure from 1980 to
      the end of 1992 (81 APE and 107 AR), followed for 5 years, evaluating their
      influence on the incidence of the recurrences. METHODS: The patients were
      enrolled at random in the two surgical groups, provided that a radical excision
      of the tumour, with only two limits: the level of the lesion from the anal verge
      and the presence of a severe incontinence instrumentally proven. TNM, Dukes
      staging, grading, and tumour location were statistically evaluated. Further
      primary suture vs. packing of the perineal wound in APE and handsewn vs. stapled
      anastomosis in AR were compared in relation with the incidence of LR. RESULTS:
      The overall local recurrence rate was 19.2% (32/167), in details 19.7% for APE
      and 18.5% for AR. Similar recurrence rates were observed following both
      procedures, matching the patients according to the Dukes stage and different
      details of techniques. A slight statistically significant difference was found as
      far as the tumour location is concerned in the group treated with anterior
      resection (p = <0.05) because of the higher recurrence observed in AR performed
      for tumours of the lower third of the rectum in comparison with the more proximal
      level. CONCLUSIONS: The AA conclude that the choice of the right surgical
      procedure in the rectal carcinoma depends on the characteristics of the tumour
      and the conditions of the patients, provided that the oncologic indications were
      respected, because recurrence and survival rate are independent from the surgical
      approaches.

PMID- 10914828
TI  - Local excision for rectal cancer.
AB  - BACKGROUND AND OBJECTIVES: The aim of this retrospective study is to evaluate the
      results of local excision (LE) for rectal cancer for curative purposes. METHODS:
      From 1969 to December 1997, a total of 456 operations were performed for surgical
      treatment of rectal carcinoma (262 males and 194 females, mean age 66 years).
      Twenty patients (4.1%) underwent LE (7 males and 13 females, median age 65
      years). Patients were selected for LE if they met the following criteria during
      preoperative staging: tumors staged as T1-T2,N0,M0, grading G1 or G2, and
      accessible location. Types of LE performed were: 13 transanal excisions
      (Francillon's technique), 2 Mason surgeries, 2 endoscopic excisions, and 3
      transanal endoscopic microsurgeries. RESULTS: There was no in-hospital mortality
      among LE patients. Thirteen tumors were T1 and 7 were T2; all 20 were
      adenocarcinoma, 14 G1 and 6 G2. There was no specific morbidity, and aspecific
      morbidity was minimal (5%). There were no local recurrences, but 2 patients (10%)
      had secondary lesions. Five-year overall survival following LE was 87.4%.
      Comparing T1 and T2 tumors treated with abdominoperineal resection (APR) and SSR
      (17 T1 and 42 T2, all adenocarcinoma), in-hospital mortality and specific
      morbidity were respectively 1.7% (P = 0.55) and 28% (P = 0.007). There were 5
      (8.5%) local recurrences (P = 0.17) and 6 (10.2%) metastatic lesions. Five-year
      overall survival was similar to LE (88.3%; P = 0.76). CONCLUSIONS: LE for rectal
      carcinoma might only be successfully performed in selected patients with correct
      preoperative staging. In the LE cases reported five-year overall survival, local
      recurrence, and in-hospital mortality were similar to APR and SSR, while there
      was a statistically significant difference following LE in terms of specific
      morbidity.

PMID- 10914829
TI  - nm23-H1 protein expression in anal canal carcinoma: does it correlate with
      prognosis?
AB  - BACKGROUND AND OBJECTIVES: Anatomic extent is not the sole axis of classification
      of tumors and of tumor patients relevant to treatment planning and estimation of
      prognosis. This results in the need to demonstrate an improvement in prognostic
      assessment and choice of therapy achieved by consideration of factors other than
      TNM. nm23 protein does prevent tumor from metastasizing and may also play a role
      in the control of growth and development. The purpose of this study was to
      elucidate the clinical significance of nm23 expression in human anal canal
      carcinoma and to evaluate its influence on the outcome of patients after surgery
      or radiochemotherapy. METHODS: Twenty-two patients affected by anal canal
      carcinoma were evaluated. Each section was incubated with monoclonal antibody
      nm23 NDPK-A. Immunostaining was considered positive when at least 10% of the
      tumor cells were immunostained. RESULTS: nm23 immunoreactivity was detected in
      6/22 (27.3%) tumors. No significant association was found between nm23 expression
      and prognosis. CONCLUSIONS: The mechanisms causing enhanced nm23-H1 expression in
      anal canal carcinoma are unknown. Although the level and expression were not
      correlated with prognosis, activation of nm23-H1 gene might be a prerequisite for
      oncogenesis in this type of tumor, while an alternate possibility is the
      modification of cellular characteristics in relation to proliferation and/or
      differentiation as a consequence of oncogenesis.

PMID- 10914830
TI  - An unusual late radiotherapy-related complication requiring surgery in anal canal
      carcinoma.
AB  - We herein describe an unusual late radiation-related complication requiring
      surgery in a 60-year-old male affected by anal epidermoid carcinoma. The patient
      presented with obstructed defecation and ulcerated perianal lesions. The perianal
      biopsies were positive for anal squamous carcinoma. Transanal diagnostic
      investigations could not be performed because of anal stenosis. Computed
      tomography detected left inguinal lymphadenopathy and a nonhomogeneous presacral
      mass, infiltrating the rectal wall, the coccyx, and the sacrum. The patient
      underwent a colostomy, infusion of cisplatin and 5-fluorouracil, and irradiation
      of the pelvis, perianal region, and inguinal lymph nodes. In June 1997 the
      patient complained of the onset of continuous pain at the genitalia, and for
      penis necrosis he underwent penis amputation. The histologic examination was
      conclusive for postradiotherapy thrombosis. This complication could strengthen
      the hypothesis of vasculoconnective damage as the origin of long-term effects of
      radiotherapy. Probably the minimal dose in transit volume could not be achieved.
      Careful evaluation in choosing the treatment scheme is necessary if different
      options are available.

PMID- 10914831
TI  - An adequate treatment for the nipple adenoma.

PMID- 10914833
TI  - Preventing joint damage from hemophilia.

PMID- 10914832
TI  - Cancer of the anus.
AB  - Cancers of the anus, whether keratinizing squamous, nonkeratinizing, clear-cell,
      or melanoma, are infrequent neoplasms. Small keratinizing (<4 cm2) with no deep
      invasion can be controlled by local excision or laser ablation, but larger ones
      may be treated by chemoirradiation, restricting abdominoperineal resection to
      recurrences. Neither melanomas nor clear-cell cancers are curable, and local
      control is the surgical objective. Prophylactic groin dissection is not required
      but, for enlarged nodes or in the presence of a positive sentinel node biopsy,
      may be curative in many cases and palliative in all.

PMID- 10914834
TI  - Atraumatic osteonecrosis of the humeral head.

PMID- 10914835
TI  - Hypermobility syndrome--new diagnostic criteria.

PMID- 10914836
TI  - Is hypermobility a factor in fibromyalgia?

PMID- 10914837
TI  - Wallace Graham--a life in Canadian rheumatology.

PMID- 10914838
TI  - Origins and early beginnings of the Canadian Arthritis Society and the first
      rheumatic disease units in Canada.

PMID- 10914839
TI  - In the beginning...

PMID- 10914840
TI  - Suppression of collagen induced arthritis in mice utilizing plasmid DNA encoding
      interleukin 10.
AB  - OBJECTIVE: To investigate the therapeutic efficacy as well as the immunological
      effects of inoculation of an expression vector encoding interleukin 10 (IL-10) in
      murine type II collagen induced arthritis (CIA). METHODS: CIA was induced in
      DBA/1 Lac/J mice by immunization with bovine type II collagen (CII) in Freund's
      complete adjuvant (FCA), followed by immunization of CII in Freund's incomplete
      adjuvant (FIA) 3 weeks later (CIA mice). The plasmid cytomegalovirus (pCMV)
      vector encoding IL-10 (pCMV-IL-10) was inoculated intradermally into DBA/1 Lac/J
      mice (pCMV-IL-10 CIA mice) one week prior to first immunization with CII. CIA
      mice inoculated with the backbone pCMV vector instead of pCMV-IL-10(pCMV CIA
      mice), mice inoculated with the pCMV vector alone, without subsequent
      immunization with CII (pCMV-C mice), and mice not subjected to any treatment (C
      mice) were examined as controls. At the 3rd and 5th week after 2nd immunization
      with CII, booster injections of CII in FIA were administered. Foot pad
      thicknesses were measured weekly and the histopathological changes in the ankle
      joints and the titers of IgG1 (Th2 type) and IgG2a (Th1 type) isotype antibodies
      to CII were examined at the 10th week. RESULTS: pCMV-IL-10 CIA mice showed lesser
      foot pad thicknesses (p < 0.01 except at Weeks 1-3), less severe
      histopathological changes (p < 0.01 or 0.05) and lower IgG2a/IgG1 ratios of
      antibodies to CII (p <0.01) than CIA mice. CONCLUSION: Inoculation of pCMV-IL-10
      suppressed CIA through suppression of the Th 1 type immune response in CIA, and
      offers promise as a potential therapeutic strategy for rheumatoid arthritis.

PMID- 10914841
TI  - The possible role of c-fos expression in rheumatoid cartilage destruction.
AB  - OBJECTIVE: To determine the effect of c-fos on human chondrocytes and to examine
      the role of c-fos in cartilage destruction in rheumatoid arthritis (RA). METHODS:
      We examined changes in collagen synthesis by transfecting human c-fos into
      cultured human chondrocytes and evaluated expression of c-fos mRNA and
      localization of Type II collagen, matrix metalloproteinases-1 (MMP-1), and tissue
      inhibitor of metalloproteinases-1 (TIMP-1) in articular cartilage samples from
      patients with RA or osteoarthritis (OA) by in situ hybridization and
      immunohistochemistry. RESULTS: Introduction of c-fos in the chondrocytes
      decreased endogenous transcription of Type II collagen and TIMP-1, and increased
      that of MMP-1. The effect of the activating protein-1 protein on the MMP-1 and
      TIMP-1 promoters in human articular chondrocytes was analyzed by chloramphenicol
      acetyltransferase activity assay. MMP-1 promoter was clearly activated by Jun
      related proteins as well as Fos/Jun related protein heterocomplex. On the other
      hand, c-fos combined with any of the Jun related proteins failed to stimulate the
      TIMP-1 promoter, although it was activated by Fra-1 or Fra-2/Jun related protein
      heterocomplexes. Expression of c-fos mRNA was detected in chondrocytes in the mid
      and deep layers of cartilage in 11/15 patients (73%) with RA, but only in the
      superficial layer of cartilage from 2/10 patients (20%) with OA. Although TIMP-1
      staining exceeded that of MMP-1 in OA cartilage, it appeared to be less intense
      than MMP-1 staining in RA cartilage. CONCLUSION: These results suggest that
      activation of c-fos may be involved in cartilage metabolism and hence play a
      crucial role in the pathogenesis of arthritic destruction in RA.

PMID- 10914842
TI  - Estrogen and progesterone regulation of human fibroblast-like synoviocyte
      function in vitro: implications in rheumatoid arthritis.
AB  - OBJECTIVE: Despite increasing evidence regarding the significance of sex hormones
      in rheumatoid arthritis (RA), their etiopathological role and potential longterm
      effect on joint destruction remain unclear. We hypothesized that estrogen
      receptors (ER-alpha) are present in fibroblast-like synoviocytes, and 17beta
      estradiol can modulate the production and activity of matrix degrading enzymes
      produced by these cells. Thus, depending on the endocrine balance, fibroblast
      like synoviocyte activity can be suppressed or enhanced, leading to amelioration
      or exacerbation of the disease process, respectively. METHODS: By utilizing an in
      vitro cartilage invasion model, in combination with the molecular analyses of
      hormone receptors, matrix metalloproteinases (MMP) and their respective
      inhibitors, we investigated the effect of hormones (i.e., estrogen and
      progesterone) on fibroblast-like synoviocyte phenotypic changes, with particular
      emphasis on their functional interactions with cartilage. RESULTS: Our studies
      reveal the presence of functional ER-alpha in fibroblast-like synoviocytes. The
      findings indicate that estrogen exerts a stimulatory effect, while progesterone
      has an inhibitory effect on the expression of MMP, their tissue inhibitors
      (TIMP), and enzymatic activity of MMP produced by these cells. Furthermore,
      transfection of fibroblast-like synoviocytes with the ER-alpha gene resulted in
      the increased degradation and invasion of cartilage. CONCLUSION: We identified
      the presence of functional ER-alpha in fibroblast-like synoviocytes. This renders
      fibroblast-like synoviocytes as target cells for hormonal regulation. The
      regulatory effect of estrogen is partly targeted to the MMP and their respective
      inhibitors associated with fibroblast-like synoviocytes. Such studies provide a
      link between hormonal status and disease activity in RA and open new venues for
      future therapeutic intervention to combat this debilitating disease.

PMID- 10914843
TI  - Progression of radiographic joint erosion during low dose corticosteroid
      treatment of rheumatoid arthritis.
AB  - OBJECTIVE: The reported prevention of joint damage during treatment with
      prednisolone 7.5 mg daily in patients with early rheumatoid arthritis (RA)3 may
      have important implications for management of RA. We evaluated this observation
      in another patient population. METHODS: Radiographic progression rates in paired
      hand radiographs were analyzed in 824 patients with RA who participated in a 3
      year prospective, randomized clinical trial comparing the nonsteroidal
      antiinflammatory drugs (NSAID) etodolac (150 or 500 mg bid) and ibuprofen (600 mg
      qid). Disease modifying antirheumatic drugs (DMARD) were not permitted.
      Prednisone < or=5 mg daily was continued by 197 patients (mean dose 4.37 mg
      daily) who had started prednisone therapy at least 6 mo before study entry, but
      new prednisone starts were not allowed. Standardized hand/wrist radiographs were
      done yearly and at dropout; joint erosion and narrowing scores of 3 readers were
      averaged and progression rates were compared. RESULTS: Mean duration of RA was
      3.6 years (range 1-7); patients' ages were 21-78 years; 71% were women. Among the
      824 patients, those taking prednisone were more likely to have had previous
      DMARD, and at study entry had higher radiographic scores for joint erosion and
      joint space narrowing and slightly higher swollen joint counts, C-reactive
      protein values, and rheumatoid factor titers than those not taking prednisone.
      However, for the subgroup of 252 patients with RA duration of 12-24 months,
      prestudy radiographic scores were not different in those taking or not taking
      prednisone. The mean (+/-SD) monthly rate of increase in erosion scores was 0.228
      +/-0.37 for the prednisone patients and 0.206+/-0.35 for patients not taking
      prednisone (p = 0.994 by ANCOVA). The subgroup with 12 to 24 months' disease
      duration at entry also showed no significant effect of prednisone treatment on
      erosion progression. CONCLUSION: Clinically indicated low dose prednisone did not
      prevent progressive radiographic damage in 197 NSAID treated patients whose
      physicians had initiated < or =5 mg daily before study entry. The risk/benefit
      ratio of chronic low dose prednisone in early RA remains uncertain.

PMID- 10914844
TI  - Genetic association between rheumatoid arthritis and estrogen receptor
      microsatellite polymorphism.
AB  - OBJECTIVE: To investigate estrogen receptor (ER) microsatellite allele
      frequencies in patients with rheumatoid arthritis (RA), and possible associations
      of ER microsatellites with osteoporosis and disease progression. METHODS: We
      typed 144 Japanese females with RA and 200 healthy postmenopausal Japanese
      controls for ER microsatellites by polymerase chain reaction methods using
      fluorescent labeled primer and semiautomatic genotyping. Bone mineral density
      (BMD) of patients was measured in the spine by dual energy x-ray absorptiometry,
      and recent radiographs of the hands and wrists were scored according to the
      method described by Sharp, et al. RESULTS: The ER genotype was classified
      according to number of dinucleotide (thymine-adenine, TA) repeats between 10 and
      27. The frequency of allele 14 (14 repeats of TA) was significantly increased in
      patients versus controls. No association of ER microsatellites with osteoporosis
      or radiographic progression in the RA patients was noted. CONCLUSION: These
      results suggest that a genetic variation at the ER locus may be associated with
      other pathogenetic factors in patients with rheumatoid arthritis, but not with
      BMD and disease aggressiveness.

PMID- 10914845
TI  - Metatarsalgia and rheumatoid arthritis--a randomized, single blind, sequential
      trial comparing 2 types of foot orthoses and supportive shoes.
AB  - OBJECTIVE: To compare the effects of semi-rigid and soft orthoses worn in
      supportive shoes, and supportive shoes worn alone, on metatarsal phalangeal (MTP)
      joint pain. MTP joint synovitis, and lower extremity function in patients with
      rheumatoid arthritis. METHODS: Twenty-eight subjects referred to occupational
      therapy received in random order 3 interventions for 12 week trials, separated by
      2 week washouts. A crossover design compared effectiveness of interventions.
      RESULTS: Twenty-four subjects completed the study. A reduction in mean pain
      scores from baseline to final visits showed that semi-rigid orthoses had a highly
      significant effect on pain. Soft orthoses did not show a significant effect on
      pain from baseline to final visit, nor did shoes worn alone. None of the
      interventions had a significant effect on synovitis or function. CONCLUSION: Semi
      rigid orthoses worn in supportive shoes were an effective treatment for
      metatarsalgia. Supportive shoes worn alone or worn with soft orthoses did not
      provide pain relief for metatarsalgia.

PMID- 10914846
TI  - Patterns of drug use in rheumatoid arthritis.
AB  - OBJECTIVE: Treatment strategies for rheumatoid arthritis (RA) are rapidly
      evolving, but few data exist on current prescribing patterns in distinct
      populations of patients and physicians. We described patterns of drug use for RA
      in a large population including use of nonsteroidal antiinflammatory drugs
      (NSAID), disease modifying antirheumatic drugs (DMARD), and corticosteroids.
      METHODS: We identified a cohort of 10,262 New Jersey Medicaid/Medicare/PAAD
      (Pharmacy Assistance for the Aged and the Disabled) beneficiaries with at least
      one episode of care for RA between January 1, 1992, and January 1, 1995, and at
      least one episode of care after December 31, 1995. All patients were present for
      the entire study period and thus constituted a closed cohort. All filled
      prescriptions, hospitalizations, nursing home care, and physician visits during
      1995 were analyzed. RESULTS: The cohort was 67 years old on average, 82% female,
      and 63% white; 63% were enrolled in Medicaid and 9% were in a nursing home at the
      beginning of followup. During the study year, 68% of patients filled at least one
      prescription for any of the drug groups studied. The most frequently prescribed
      medication was an NSAID (57%), followed by corticosteroids (23%) and DMARD (13%).
      Thirty-nine percent of patients used only NSAID, 2% only DMARD, and 6% only
      corticosteroid. Patients taking NSAID used them on average for 3 months during
      the study year, corticosteroids for 4 months, and DMARD for over 7 months. During
      the study year, one-third of DMARD users stopped all DMARD therapy. One-third of
      prednisone users were taking doses higher than 10 mg/day. CONCLUSION: While our
      RA cohort was older than would be expected, they represent a typical Medicare and
      Medicaid or PAAD population. In this cohort of patients with a diagnosis of RA
      cared for by either general practitioners or rheumatologists, NSAID were the most
      commonly prescribed medication, with substantially lower rates of use for DMARD
      and corticosteroids. Drug discontinuation and medication switching were common.

PMID- 10914847
TI  - Concentration-effect relationship of hydroxychloroquine in patients with
      rheumatoid arthritis--a prospective, dose ranging study.
AB  - OBJECTIVE: A 6 month prospective randomized double blind study was conducted to
      investigate hydroxychloroquine dose concentration-effect relationships in people
      with rheumatoid arthritis. METHODS: Patients were randomized in 2 groups: one
      group received 200 mg hydroxychloroquine sulfate daily (A) and one group received
      400 mg daily (B). Each month, 8 disease variables were assessed, adverse events
      recorded, and hydroxychloroquine blood concentrations determined. RESULTS: Twenty
      three patients were included: 10 in group A and 13 in group B. After 6 months of
      therapy, a significant improvement in disease activity was noted for 6 criteria
      with no statistical differences between groups: pain (assessed by a visual analog
      scale), joint scores (swelling and tenderness), impairment in daily living
      activity (18 activities graded 0 to 8), patient assessment of disease state, and
      erythrocyte sedimentation rate. Hydroxychloroquine steady-state blood
      concentrations (Month 6) were significantly different between groups (mean +/-
      SD): 450.6 +/- 285.3 ng/ml (A) vs 870.3 +/- 329.3 ng/ml (B) (p = 0.0001). Steady
      state concentrations were correlated with the daily dose (r = 0.63, p = 0.005),
      the improvement in activity of daily living (r = 0.49, p = 0.03), and the
      improvement in joint tenderness score (r = 0.47, p = 0.038). CONCLUSION: The data
      indicate that hydroxychloroquine is an effective therapy, but there were no
      further improvements observed in the group receiving 400 mg daily compared to
      those receiving 200 mg. There were some correlations between hydroxychloroquine
      steady-state blood concentrations and effects.

PMID- 10914848
TI  - The importance of gastrointestinal (GI) symptom severity in rheumatoid and
      osteoarthritis: symptom rates and risk for GI hospitalization.
AB  - OBJECTIVE: To determine the prevalence and stability of gastrointestinal (GI)
      symptoms in outpatients with rheumatoid arthritis (RA) and osteoarthritis (OA);
      to determine the specific symptoms that contribute to severity; and to determine
      the predictive value of GI symptoms and GI severity on the risk of future GI
      hospitalization. METHODS: A questionnaire survey was mailed to 1221 patients with
      RA and OA on a continuing 6 month schedule. Patients completed an average of 4.4
      questionnaires (n = 5,047). Questionnaires included a visual analog scale GI
      severity scale, and questions regarding GI hospitalizations and specific GI
      symptoms. Hospitalizations that were reported as relating to the GI system were
      audited by checking hospital records. RESULTS: We found 57.5%, 40.2%, and 25.5%
      of patients had at least one assessment in which they had a GI symptom severity
      of 0.25-0.99, 1.00-1.99, and 2.00 or greater, respectively. Overall 74.9% had at
      least one score of 0.25 or greater, and 73.6% had one score of < 0.25, the cutoff
      for GI symptoms. By contrast, 6.45% had a GI hospitalization, and in only 0.75%
      of the questionnaire assessments were hospitalizations noted. Pyrosis and peptic
      ulcer symptoms were common, and were found in 62.5% and 42.4% of patients and
      28.2% and 12.9% of observations, respectively. Among patients reporting GI
      severity scores between 2 and 3, roughly 60% and 45% reported the presence of
      pyrosis and peptic ulcer symptoms, respectively. The presence of a GI severity
      score > or = 0.25 was associated with 2.8-3.0-fold increase in the risk of
      hospitalization over the following 6 months. CONCLUSION: These data suggest that
      symptoms have an importance of their own that relates to quality of life,
      regardless of the risk of serious GI events like hospitalization, and that more
      attention should be placed on symptoms and symptom severity in future research.
      In spite of the statistical predictive value of GI symptom severity on future
      hospitalizations, it is important to recognize that rate of GI hospitalization
      increases from 0.92 per 100 patient-years to only 2.90 per 100 patient-years when
      the GI symptom scale goes from approximately zero to positive values. Thus, in
      spite of its statistical predictive ability, GI symptom severity is a poor
      clinical predictor of the hospitalizations that occur in patients with rheumatic
      diseases. Instead, GI symptom severity and specific GI symptoms have a separate
      importance to patients.

PMID- 10914849
TI  - The comparative risk and predictors of adverse gastrointestinal events in
      rheumatoid arthritis and osteoarthritis: a prospective 13 year study of 2131
      patients.
AB  - OBJECTIVE: It has been suggested that rheumatoid arthritis (RA) itself may be a
      risk factor for adverse gastrointestinal (GI) events, but this hypothesis has not
      been studied in a large sample, nor has the effect of time on risk factors been
      studied. We investigated rates and risk factors for GI events in RA and
      osteoarthritis (OA) and assessed the additional risks conveyed by having RA.
      METHODS: A prospective study of patients with OA and RA from a single center was
      undertaken using questionnaires mailed at 6 month intervals. The relationship
      between drug therapy and GI events was assessed in the same 6 month time frame.
      Over 13 years of biannual assessments, 2,131 patients were studied for serious GI
      events and adverse GI symptoms during 9,621 patient-years of observation.
      RESULTS: The incidence rate (IR) for GI hospitalization was 1.56 and 1.28 per 100
      patient-years, and for GI bleeding or perforation was 0.50 and 0.58 for RA and
      OA, respectively. After controlling for age, sex, nonsteroidal antiinflammatory
      drug (NSAID) and steroid use, the incidence rate ratio (IRR) for RA versus OA did
      not differ for hospitalization [IRR 1.07 (95% CI 0.66, 1.74)] or for bleeding or
      perforation [IRR 0.63 (95% CI 0.29, 1.35)]. In multivariate analyses for both
      groups combined, the IRR was 2.95 (2.05, 4.24) for prednisone use, 1.41 (1.08,
      1.85) for NSAID use, and 1.46 (1.22, 1.74) for every 10 year increase in age. In
      additional multivariate models, Health Assessment Questionnaire disability was
      also a significant risk factor. During the study period, the odds of NSAID use
      decreased 2.94 times per 10 year period, while the odds of prednisone use
      increased by 1.49. Dysphagia [IRR 1.11 (1.00, 1.24)], anorexia [IRR 1.13 (1.03,
      1.23)], nausea [IRR 1.13 (1.04, 1.25)], heartburn [IRR 1.12 (1.05, 1.19)],
      vomiting [IRR 1.20 (1.02, 1.42)], peptic ulcer symptoms [IRR 1.20 (1.11, 1.29)],
      and abdominal pain [IRR 1.11 (1.01, 1.22)] were associated with NSAID use, but
      not with steroids. CONCLUSION: Patients with RA and OA do not differ in the rates
      and risk factors for GI hospitalizations and symptoms after controlling for age,
      steroid use, NSAID use, or (for OA) body mass index. Prednisone is a more
      important risk factor among patients with RA than NSAID.

PMID- 10914850
TI  - A randomized controlled trial to evaluate the effectiveness of an exercise
      program in women with rheumatoid arthritis taking low dose prednisone.
AB  - OBJECTIVE: To evaluate the effects of a 12 month, weight bearing, aerobic
      exercise program on disease activity, physical function, and bone mineral density
      (BMD) in women with rheumatoid arthritis (RA) taking low dose prednisone.
      METHODS: A group of women with RA (n = 23) not receiving steroid therapy and in
      American College of Rheumatology functional class I or II was compared to 30
      steroid treated patients with similar demographics. The latter group was
      randomized to usual care (n = 16) or an aerobic, weight bearing exercise program
      (n = 14) 3 times a week for 12 months. All subjects were recruited from an
      outpatient rheumatology clinic or physical therapy department and met the study
      inclusion criteria. Outcome measures included disease activity (erythrocyte
      sedimentation rate, active joint count), physical function (Health Assessment
      Questionnaire disability index, activity level) and BMD of the spine and femoral
      neck (by dual energy projection radiology). RESULTS: Subjects in the exercise
      group had a small but nonsignificant decrease in disease activity and
      statistically significant improvements in function (p = 0.05) and activity levels
      (p = 0.05). BMD remained unchanged in the exercise group, decreased significantly
      (p = 0.004) in the nonsteroid comparison group (hip), and changed
      nonsignificantly in the control group. However, between-group changes in spinal
      BMD of the steroid treated groups was not significant (p = 0.09). CONCLUSION:
      Women with RA taking low dose steroid therapy can safely participate in a
      dynamic, weight bearing exercise program with positive effects on their physical
      function, activity and fitness levels, and BMD with no exacerbation of disease
      activity.

PMID- 10914851
TI  - Influenza virus vaccination of patients with systemic lupus erythematosus:
      effects on disease activity.
AB  - OBJECTIVE: To determine whether vaccination of patients with systemic lupus
      erythematosus (SLE) with influenza virus vaccine is associated with exacerbation
      of SLE. METHODS: The study population comprised 24 patients with SLE who received
      influenza vaccine (cases group) and 24 other SLE patients who did not receive the
      vaccine (controls group). The primary outcome measure was the SLE Disease
      Activity Index (SLEDAI) scores 6 weeks and 12 weeks after vaccination. Secondary
      outcome measures included: number of SLE flares, defined as any increase in the
      SLEDAI > or = 3 points, and activity of renal disease. Repeated measurements
      MANOVA was used to compare the SLEDAI scores of the cases and controls. RESULTS:
      All patients were women. The mean age at enrollment into the study was 46.1 and
      40.6 years for the cases and controls, respectively. The mean disease duration
      was 9.1 for the cases and 9.3 years for the controls. SLEDAI scores for the cases
      and controls were 6.6 and 8.9 at vaccination, 4.9 and 6.8 at Week 6, and 5.1 and
      6.7 at Week 12, respectively. The SLEDAI scores of the cases and controls at the
      3 different assessments were not statistically different (p = 0.28). However,
      within each group the decrease in the SLEDAI over time was statistically
      significant (p = 0.02). Three and 6 flares were observed in the cases and
      controls, respectively, (p = 0.27) during the 12 weeks of followup. Improvement
      in the renal disease was observed in the cases and controls. CONCLUSION:
      Influenza virus vaccine is safe for patients with SLE. Patients with SLE should
      be encouraged to receive the vaccine according to the recommendation given by the
      Immunization Practices Advisory Committee.

PMID- 10914852
TI  - Severity of seropositive isolated Raynaud's phenomenon is associated with
      serological profile.
AB  - OBJECTIVE: To examine the relationship between the clinical severity of
      seropositive isolated Raynaud's phenomenon (RP) and its serological background by
      analyzing digital blood flow data obtained by laser Doppler flowmetry (LDF).
      METHODS: We analyzed digital blood flow by LDF in 13 healthy volunteers, 55
      patients with seropositive isolated RP, and 13 patients with anti-Scl-70 antibody
      positive systemic sclerosis (SCL). The serological profiles of patients with RP
      were as follows: 30 patients had the anti-centromere antibody (C) and 19 the anti
      RNP antibody (RNP). We designated the RP in each patient group as C-RP, RNP-RP,
      and SCL-RP. We used an "arm-raising test" by which blood pressure could be
      passively depressed, and the cold provocation test, which induced
      vasoconstriction through the sympathetic reflex. We defined 2 variables, the
      recovery velocity after cold exposure (RV-CE) and the increase in the amplitude
      of the digital pulse wave during the arm-raising test (IA-AR), that are the most
      reliable and sensitive variables indicating the severity of RP. RESULTS: Both RV
      CE and IA-AR correlated significantly with the clinical severity of RP. In IA-AR
      and RV-CE, there was a significant difference between C-RP and RNP-RP (IA-AR
      107.1 +/- 25.63 vs 37.4 +/- 17.25%; RV-CE 0.0667 +/- 0.010 vs 0.035 +/- 0.0096
      V/s), showing that C-RP tended to be less severe than RNP-RP. CONCLUSION: We
      defined 2 variables that correlated with the clinical severity of RP; using them
      we found that anti-centromere antibody positive RP is less severe than RNP-RP

PMID- 10914853
TI  - Exhaled nitric oxide in systemic sclerosis: relationships with lung involvement
      and pulmonary hypertension.
AB  - OBJECTIVE: To measure nitric oxide (NO) concentration in exhaled air of patients
      with systemic sclerosis (SSc) and to investigate its relationships with lung
      involvement, complicated or not by pulmonary hypertension (PH). METHODS: Exhaled
      NO was measured by chemiluminescence in 47 patients with SSc (16 with PH) and in
      30 controls. All the patients underwent Doppler echocardiography to assess
      pulmonary artery pressure (PAP), lung function tests, and thin section computed
      tomographic scans of the lung to quantify the extent of fibrosing alveolitis.
      RESULTS: Exhaled NO levels were higher in patients with SSc (16.6 +/- 9.1 ppb),
      particularly those with interstitial lung disease (ILD) (18.3 +/- 10.4 ppb),
      compared to controls (9.9 +/- 2.9 ppb; p < 0.0001). In patients with PH, exhaled
      NO was less than in patients without PH (10.7 +/- 5.9 vs 19.6 +/- 9 ppb,
      respectively; p < 0.001), and patients with PH without ILD had even lower exhaled
      NO than patients with PH and ILD (6.6 +/- 1.1 vs 12.6 +/- 6.3 ppb; p = 0.004).
      There was an inverse correlation between PAP and exhaled NO (r = 04).53, p =
      0.004). Exhaled NO was not correlated to age, disease duration, current therapy,
      or form of disease (limited or diffuse). CONCLUSION: The increased concentration
      of exhaled NO in patients with SSc may reflect respiratory tract inflammation.
      The relatively low value of exhaled NO in patients with PH and the negative
      correlation between PAP and exhaled NO suggest the important role of NO in
      regulating pulmonary vascular resistance in patients with SSc.

PMID- 10914854
TI  - Psoriatic arthritis and human immunodeficiency virus infection in Zambia.
AB  - OBJECTIVE: To characterize the clinical features of psoriatic arthritis (PsA) in
      black Zambians and the association of PsA with human immunodeficiency virus (HIV)
      infection. METHODS: Patients attending an arthritis clinic in a 40 month period
      who exhibited psoriasiform lesions were assessed clinically and tested for the
      presence of antibodies to HIV. RESULTS: Of 702 new attendees with inflammatory
      arthritis 28 were designated as PsA and 27 of these were HIV+. Sixteen patients
      (60%) at presentation were in WHO clinical stage I (no disease or lymphadenopathy
      alone) compared to 2 in stage 4 (acquired immune deficiency syndrome, AIDS).
      Arthritis and psoriasis developed simultaneously in 20 patients. The arthritis is
      predominantly polyarticular, lower limb, and progressive. Amelioration was noted
      with onset of AIDS. Psoriasis was commonly an extensive guttate-plaque admixture
      and nonremittive with onset of AIDS. CONCLUSION: PsA is almost universally
      associated with HIV infection in black Zambians. The clinical features are
      similar to those described in Caucasians with HIV associated PsA.

PMID- 10914855
TI  - Genotype-phenotype assessment of common genotypes among patients with familial
      Mediterranean fever.
AB  - OBJECTIVE: To study genotype-phenotype correlation for the 4 most common
      genotypes found among patients with familial Mediterranean fever (FMF). METHODS:
      Thirty patients with the M694V/M694V genotype, 32 with M694V/V726A genotype, 25
      with M694V/E 148Q genotype, and 21 with V726A/V726A genotype were assessed for
      various clinical manifestations of FMF, and overall disease severity. RESULTS:
      Patients with the M694V/M694V genotype were found to have an earlier age of
      onset, higher frequency of joint involvement, higher frequency of erysipelas-like
      erythema, and required higher doses of colchicine to control the disease compared
      to the other 3 genotypes. CONCLUSION: The M694V/M694V genotype is associated with
      more severe disease compared to other common genotypes in patients with FMF.

PMID- 10914856
TI  - Effect of low level lead exposure on hyperuricemia and gout among middle aged and
      elderly men: the normative aging study.
AB  - OBJECTIVE: To determine whether longterm lead accumulation is associated with
      hyperuricemia and gouty arthritis among middle aged and elderly men. METHODS: In
      a retrospective cohort study, 777 male participants were evaluated between August
      1991 and October 1996 in the Department of Veterans Affairs Normative Aging
      Study, a 35 year longitudinal study of aging. We examined the development of gout
      and an increased uric acid level in relation to lead, adjusting for other known
      risk factors. Lead levels were measured in blood and by K x-ray fluorescence (K
      XRF) technique in tibial (cortical) and patellar (trabecular) bone. RESULTS:
      Blood lead levels in this mostly Caucasian (97%) population were low (mean 5.9
      microg/dl, SD 3.5). Bone lead levels were comparable to those described in other
      general populations. In a multivariate analysis adjusting for the risk factors,
      age, body mass index, diastolic blood pressure, alcohol intake, and serum
      creatinine level, there was a positive association between patellar bone lead and
      uric acid levels (p = 0.02). Of 777 participants, 52 (6.7%) had developed gouty
      arthritis. In logistic regression of similar covariates, body mass index (p <
      0.0001) and serum creatinine level (p = 0.005) were the strongest determinants of
      gout; neither bone nor blood lead levels predicted gout in this cohort.
      CONCLUSION: The longterm accumulation of lead is associated with an increased
      uric acid level in middle aged and elderly men. However, this study shows no
      association between lead and gouty arthritis at the levels arising from community
      exposure.

PMID- 10914857
TI  - Effect of hyaluronan on chondrocyte apoptosis and nitric oxide production in
      experimentally induced osteoarthritis.
AB  - OBJECTIVE: Nitric oxide (NO) plays an important role in cartilage degeneration,
      and NO donors induce chondrocyte apoptosis. This study evaluated the effect of
      intraarticular injections of hyaluronan (HA) on chondrocyte apoptosis and NO
      production using an experimental osteoarthritis (OA) model. METHODS: Thirty-six
      New Zealand white rabbits underwent unilateral anterior cruciate ligament
      transection (ACLT), and were divided into 3 groups. Four weeks after ACLT, the HA
      group started intraarticular HA injections once a week for 5 weeks; the vehicle
      group started to receive the carrier of HA; the no injection group received no
      treatment. All ACLT knees were harvested at Week 9 and evaluated for OA severity.
      Culture supernatants of the cartilage were analyzed for nitrite concentration.
      Cartilage sections were analyzed by TUNEL for apoptosis and by
      immunohistochemistry for nitrotyrosine. RESULTS: OA in the HA group was less
      severe than the other 2 groups. The number of apoptotic chondrocytes was
      significantly lower in the HA group. HA injection did not influence NO production
      in cartilage. CONCLUSION: HA protects against chondrocyte apoptosis during the
      development of OA, while it may not have definite effects on NO production in the
      joints. These inhibitory effects of HA on chondrocyte apoptosis may play a role
      in its mechanism of action in chondroprotection.

PMID- 10914858
TI  - Content and sulfation pattern of keratan sulfate in hip osteoarthritis using high
      performance liquid chromatography.
AB  - OBJECTIVE: To determine the content and sulfation pattern of keratan sulfate (KS)
      in synovial fluid (SF) from patients with hip osteoarthritis (OA) and investigate
      its significance as a marker of cartilage matrix metabolism. METHODS: Hip SF
      samples were aspirated from 50 patients with OA. KS in the samples was digested
      to 2 disaccharide isomers, beta-galactosyl-(1-4)-6-0-sulfo-N-acetylglucosamine
      (L2) and beta-6-0-sulfo-galactosyl-(I-4)-6-0-sulfo-N-acetylglucosamine (LA) by
      keratanase II. Concentrations of these disaccharide isomers were determined by
      high performance liquid chromatography (HPLC), and their levels were investigated
      in relation to radiological stage of disease. RESULTS: Analysis of covariance
      (age as covariate) showed that the L2 levels in advanced stage OA were
      significantly lower than in early stage OA (p < 0.0001). L2 levels in terminal
      stage OA were also significantly lower than in early stage OA (p < 0.0001);
      however, no significant difference was observed between the L2 levels in advanced
      and terminal stage OA (p = 0.516). There were no significant differences in the
      levels of L4, L2 + L4, or the ratio of L4 to L2 at each disease stage.
      CONCLUSION: The levels of KS related disaccharide isomer vary with severity of
      disease in hip OA. Analysis of these KS related disaccharide isomers by HPLC
      provides information on both the content and sulfation pattern of KS in SF,
      reflecting the metabolism of cartilage aggrecan.

PMID- 10914859
TI  - Adhesion of transplanted chondrocytes onto cartilage in vitro and in vivo.
AB  - OBJECTIVE: The specific objectives of this study using organ culture were (1) to
      transplant chondrocytes onto an intact cartilage surface; (2) to genetically
      modify endogenous and transplanted chondrocytes; and (3) to assess the ability of
      these cells to continually express a gene product. The specific objective with in
      vivo experiments was to transplant chondrocytes with intraarticular injections to
      cartilage. METHODS: Fluorescent membrane and intracellular dyes were used in
      conjunction with confocal microscopy to observe the integration of transplanted
      chondrocytes into cartilage both in vitro and in vivo. The distribution and
      duration of binding of rat, canine, and bovine chondrocytes to cartilage explants
      and the duration of expression of genes transduced into the transplanted
      chondrocytes were also determined. We used the vector AdlacZ, an E1 and E3
      deleted replication defective adenoviral vector that contains the beta
      galactosidase gene driven by the beta-actin promoter and the cytomegalovirus
      enhancer. RESULTS: The transplanted chondrocytes had a patchy distribution after
      in vitro or in vivo transplantation and buried themselves within the cartilage
      over time. Chondrocytes infected with the adenoviral vector AdlacZ soon or well
      after transplant to cartilage explants were maintained on the cartilage and
      continued throughout the duration of each trial to produce beta-galactosidase
      coded by the adenoviral vector. The cartilage plugs were infected with AdlacZ at
      2 days or one, 2, 5, or 8 weeks after the chondrocytes were transplanted. The
      cartilage slices were then cultured from 15 days for chondrocytes infected at 8
      weeks to 60 days for chondrocytes infected at 2 days post-transplant before
      determining the expression of beta-galactosidase. CONCLUSION: These results
      support the possibility of repairing cartilage by intraarticular injections of
      chondrocytes. Transduction of chondrocytes with genes producing a variety of
      matrix promoting proteins should further enhance the reconstruction of
      osteoarthritic cartilage.

PMID- 10914860
TI  - The zygapophyseal joint determines morphology of the enthesophyte.
AB  - OBJECTIVE: To determine the contribution of zygapophyseal joint ankylosis on the
      morphology of the spinal enthesophyte. METHODS: Radiographic analysis of lumbar
      spine in ankylosing spondylitis (AS) patients with different types of
      enthesophytes. Computerized axial tomographic analysis of the zygapophyseal (ZA)
      joints of the lumbar spine of AS patients with chunky enthesophytes and bridging
      syndesmophytes. RESULTS: Four patients with AS were selected for the simultaneous
      presence of chunky enthesophytes and bridging syndesmophytes. At the levels with
      bridging syndesmophytes at least one ZA joint was ankylosed. At the levels with
      chunky enthesophytes alone the ZA joints were not ankylosed. CONCLUSION: The
      morphology of the enthesophytes is influenced by the presence of ankylosis in the
      ZA joint.

PMID- 10914861
TI  - Articular cartilage is more susceptible to blood induced damage at young than at
      old age.
AB  - OBJECTIVE: It has been shown that cartilage is damaged upon intraarticular
      hemorrhage. We investigated differences in the susceptibility of cartilage from
      young adult and old animals to blood induced joint damage in a canine in vivo
      model. METHODS: Right knees of 6 young adult beagles (aged 2.2 +/- 0.1 yrs) and 6
      old beagles (7.4 +/- 0.3 yrs) were intraarticularly injected twice in 4 days with
      autologous blood. Dogs were killed 4 or 16 days after the first injection and
      cartilage matrix proteoglycan content and synthesis and collagen damage were
      determined. RESULTS: Shortly after blood injection (Day 4), proteoglycan
      synthesis was inhibited and the proteoglycan content of the cartilage was
      decreased in both groups. However, the degree of the inhibition of proteoglycan
      synthesis was significantly greater in young adult animals than in old animals.
      On Day 16 proteoglycan synthesis was increased in both young adult and old
      cartilage, but more elevated in old cartilage. The proteoglycan content remained
      decreased in both young adult and old cartilage, but significantly more so in
      young adult cartilage than in old cartilage. CONCLUSION: Results suggest that
      intraarticular bleeding influences cartilage metabolism and repair, and that the
      cartilage of young adult animals is more susceptible to these influences than
      cartilage of old animals. Differences in the aging of chondrocytes and age
      related changes in matrix integrity may be involved. Prevention and appropriate
      treatment of joint bleeding is indicated and this is especially relevant for
      young adult cartilage.

PMID- 10914862
TI  - Health related quality of life outcomes after total hip and knee arthroplasties
      in a community based population.
AB  - OBJECTIVE: To quantify the magnitude of change seen with pain, function, and
      quality of life outcomes 6 months after total hip and knee arthroplasties (THA,
      TKA) within a community based cohort of a regional health district. METHODS: An
      inception cohort of 504 patients who received primary THA (228) or TKA (276) was
      prospectively followed. All patients resided in the community and were assessed
      within one month prior to surgery and 6 months postoperatively. Health related
      quality of life measures were evaluated with the Western Ontario and McMaster
      Universities (WOMAC) Osteoarthritis Index and the Medical Outcome Survey Short
      Form SF-36. Perioperative factors were extracted from medical charts. Health
      services utilization data were collected from regional health databases. RESULTS:
      Over 75% of patients reported improvement in joint-specific pain and function,
      regardless of the type of joint replaced. Other health dimensions such as social
      function, bodily pain, physical function, vitality, and general health showed
      significant improvement after surgery. Those psychosocial dimensions with modest
      changes had baseline values comparable to age and sex adjusted normal values;
      whereas, bodily pain and physical function, which had large changes, had values
      lower than the normal values. Ninety-one percent of patients receiving THA were
      satisfied with their surgery, whereas 77% were satisfied with their TKA. The
      average length of stay was 7 days and the in-hospital complication rate was 0.34
      per patient. CONCLUSION: Large improvements were reported for pain and function
      after joint arthroplasties, while small to moderate changes were seen in other
      areas related to quality of life. Patients with hip arthroplasties showed greater
      improvement in pain and function and were more satisfied with their outcomes than
      patients with knee arthroplasties. Although pain and function show large
      improvements, bodily pain and physical function were less than the values
      reported in the general population.

PMID- 10914863
TI  - Determinants and outcomes of inpatient versus home based rehabilitation following
      elective hip and knee replacement.
AB  - OBJECTIVE: There are large variations in practice patterns and costs of
      rehabilitation following total joint replacement (TJR). We evaluated the
      determinants of rehabilitation setting (home based vs inpatient) after TJR, and
      its influence on early functional outcomes. METHODS: We studied a retrospective
      cohort of 146 primary total hip and knee replacements. Ninety-six patients
      completed a mailed survey consisting of the Western Ontario and McMaster
      University Osteoarthritis Index (WOMAC), the Medical Outcomes Survey Short Form
      36 (SF-36), and a satisfaction questionnaire. RESULTS: The mean age of the cohort
      was 66 years, 70% were women, and osteoarthritis was the primary diagnosis in
      79%. Thirty-nine percent received home based rehabilitation. Determinants of home
      based rehabilitation included preference for home based rehabilitation, male sex,
      and knowledge regarding TJR. At a mean followup of 8 months post TJR, there were
      no significant differences between the inpatient and home based rehabilitation
      groups with respect to the WOMAC, SF-36, and satisfaction scores. CONCLUSION.
      These results support continued use of home based rehabilitation.

PMID- 10914864
TI  - Effect of calcitriol on bone mineral density in premenopausal Chinese women
      taking chronic steroid therapy. A randomized, double blind, placebo controlled
      study.
AB  - OBJECTIVE: To study the effect of chronic steroid therapy on bone mineral density
      (BMD) in premenopausal women with normal menstrual cycles and its treatment.
      METHODS: A double blind placebo controlled study to evaluate 81 premenopausal
      women with systemic lupus erythematosus (SLE), aged 31.1 +/- 6 years, taking
      chronic steroid therapy, with a mean cumulative prednisone dose of 28 +/- 16.2 g.
      They were randomly allocated to 3 groups: Group 1: 0.5 microg calcitriol and 1200
      mg calcium daily; Group 2: 1,200 mg calcium and placebo calcitriol; and Group 3:
      both placebo calcitriol and placebo calcium. RESULTS: Baseline T score at the
      lumbar spine was > -1 in 56.8% and < -2.5 in 3.7% of the patients. At the end of
      2 years, patients in the calcitriol group exhibited a significant increase of 2.1
      +/- 2.4% in BMD at the lumbar spine compared to baseline value (p < 0.05). This
      change was not significantly different from the respective change in either
      calcium or placebo group (0.4 +/- 2.9% and 0.3 +/- 3.5%, respectively). No
      significant changes were observed in any treatment group in BMD at the hip or
      radius. Alkaline phosphatase increased both in the placebo (baseline: 57.5 +/-
      17.5 IU/I; year 2: 60.9 +/- 15.3 IU/A) and the calcium group (baseline: 53.6 +/-
      16.6 IU/I; year 2: 59.0 +/- 22.8 IU/1), but this increase reached statistical
      significance only in the calcium group, while the same variable remained stable
      in the calcitriol group (baseline: 53.9 +/- 14.1 IU/I; year 2: 54.6 +/- 12.3
      IU/I). CONCLUSION: Premenopausal women with SLE taking prolonged steroid therapy
      had lower BMD but showed no significant bone loss over the 2 year study period.
      The beneficial effect of calcitriol treatment in these premenopausal women was
      small, at least when it was instituted late in the course of steroid therapy.

PMID- 10914865
TI  - Atraumatic osteonecrosis of the humeral head.
AB  - OBJECTIVE: To define the epidemiology, clinical and radiographic presentation,
      treatment, and prognosis of atraumatic osteonecrosis of the humeral head.
      METHODS: Of the 1,056 patients managed for osteonecrosis of any joint between
      July 1, 1974, and December 1, 1996, 127 shoulders in 73 patients were treated for
      atraumatic osteonecrosis of the proximal humerus. Clinical and radiographic
      characterization of this patient cohort was performed. RESULTS: At presentation,
      there were 47 women and 26 men with a mean age of 41 years (range 20-60).
      Numerous associated factors were noted: alcohol use (38%), moderate smoking
      (30%), asthma (8%), and nephrosis (3%). A corticosteroid association was noted in
      60 patients (82%) and 42 of the patients (58%) had an immunocompromising disease.
      The severity of humeral head osteonecrosis did not correlate with dose or
      duration of corticosteroid therapy. According to the modified Ficat and Arlet
      radiographic staging system, there were 20 shoulders with Stage I disease, 55
      shoulders with stage II disease, and 52 shoulders with Stage ITI or IV disease.
      Seventy-four of the shoulders treated with core decompression (78%) had good to
      excellent clinical outcomes at a mean followup of 6 years (range 2-21). Fourteen
      of the 16 patients (88%) treated with hemiarthroplasty or total shoulder
      arthroplasty were clinically successful at a mean followup 4 years (range 2-11).
      CONCLUSION: We observed a low incidence of humeral head involvement in the
      osteonecrosis patient cohort (7% of all osteonecrosis patients), and a high
      incidence of corticosteroid use (82%). hip involvement (81%), and bilateral
      disease (74%). Osteonecrosis of the humeral head should be suspected in patients
      presenting with shoulder pain and a history of osteonecrosis in other joints. Hip
      screening for osteonecrosis is advocated in patients with shoulder involvement.
      Early detection of shoulder osteonecrosis may permit a more conservative, joint
      sparing approach as an alternative to surgical management.

PMID- 10914866
TI  - Joint hypermobility and primary fibromyalgia: a clinical enigma.
AB  - OBJECTIVE: To investigate the association of joint hypermobility (JH) and primary
      fibromyalgia (FM). METHODS: Eighty-eight patients admitted with widespread pain
      and 90 matched healthy controls were blindly evaluated according to criteria for
      the presence of JH and FM. RESULTS: Fifty-six patients initially recognized as
      having FM met the American College of Rheumatology (ACR) diagnostic criteria for
      FM and 6 of 90 healthy controls had these criteria at the subsequent blinded
      examination. The frequency of JH was 8% in patients with FM and 6% in subjects
      without FM (p > 0.05). Interestingly, JH was found in 10 of 32 "FM" patients
      (31%) who had not exactly met the ACR criteria for FM. The occurrence of JH was
      more common in these patients compared to controls (p < 0.001). In total, 16% of
      patients evaluated with widespread pain had associated with JH. CONCLUSION: Some
      patients who have clinical symptoms of FM but do not exactly meet the ACR
      criteria could in fact have JH, and these patients may be misdiagnosed as having
      FM. Widespread pain is associated with JH in women under age 50, with some of
      them fulfilling ACR tender point criteria for FM.

PMID- 10914867
TI  - The revised (Brighton 1998) criteria for the diagnosis of benign joint
      hypermobility syndrome (BJHS).

PMID- 10914868
TI  - A bioethics education program in pediatric rheumatology.
AB  - The medical care of children by pediatric rheumatologists may be ethically very
      complex. Medical trainees and members of the multidisciplinary health care team
      must be sensitive to and knowledgeable about ethical issues relevant to the care
      of their patients, and capable of ethical reasoning. Members of the Bioethics
      Department and the Division of Rheumatology at the Hospital for Sick Children
      have cooperatively developed a Bioethics Education Program with a curriculum
      tailored to meet the needs of the health care team. The quarterly ethics seminars
      are case based and interdisciplinary. Topics addressed include the nature of the
      patient-practitioner relationship, research with child participants, the
      developing autonomy of the child, the child's "best interests," and consent

PMID- 10914869
TI  - Sex, reproduction, and gynecological disease in young adults with a history of
      juvenile chronic arthritis.
AB  - OBJECTIVE: To study the effect of chronic disease of childhood on aspects of
      reproduction in young adults with a history of juvenile chronic arthritis (JCA).
      METHODS: Demographic data, clinical features of JCA, previous medical treatment,
      reproductive events, contraception, wish for children, sexuality, and
      gynecological disease were evaluated by means of a questionnaire in 126 women and
      35 men with JCA and their age matched healthy counterparts. RESULTS: Median age
      of patients and controls was 24 years. Median age at menarche was 13 years in
      female patients and controls. Female patients who shared characteristics of
      marital status with their healthy counterparts showed a similar attitude to
      sexual activity, contraception, wish for children, age at first child, and
      duration of lactation. Fertility was not impaired in JCA, but fecundity was
      significantly reduced. Also, pregnancy outcome was less successful in women with
      JCA, shown by a significantly increased rate of miscarriage. When analyzing the
      occurrence of gynecological disease, a higher proportion of patients had
      metrorrhagia, pelvic inflammatory disease, and surgery for ovarian cysts. Males
      with JCA had greater difficulties than both healthy males and female patients in
      establishing a permanent relationship to the opposite sex. CONCLUSION: Our study
      shows that a history of JCA in young men and women can influence several aspects
      of reproductive behavior and health. Health care providers counseling adolescents
      with JCA need to be aware of these problems.

PMID- 10914870
TI  - Tamale foot: deposit of acid mucopolysaccharides in the synovial sheaths of
      extensor tendons of the foot, resembling tendinitis, in a patient with juvenile
      ankylosing spondylitis.
AB  - We describe a clinical case of juvenile ankylosing spondylitis (AS) that
      developed "pseudo-chronic tendinitis" of the foot. A 20-year-old male patient had
      HLA-B27 positive juvenile AS since he was 13 years old. At the age of 19 he
      presented chronic pain in the dorsum of the left foot. Examination disclosed an
      increased volume of the tarsal dorsum, with rubbery consistency, with no evidence
      of venous or lymphatic insufficiency, godette, or inflammation in laboratory
      tests, giving the foot the appearance of a tamale. Synovectomy of the foot
      extensor tendon sheath was followed by relief of pain and swelling.
      Histopathological study showed a deposit of acid mucopolysaccharides (MPS) with
      no inflammatory cell infiltrate. Tamale foot in juvenile AS may develop as a
      consequence of acid MPS deposit with no evidence of synovial inflammation. The
      good response to synovectomy suggests this is the preferred treatment for tamale
      foot.

PMID- 10914871
TI  - Hepatitis A infection mimicking adult onset Still's disease.
AB  - Fever, rash, and arthritis may be components of the prodrome of viral hepatitis.
      In the absence of jaundice and abnormal liver function tests, this form of
      polyarthritis is easily confused with primary autoimmune diseases. Whereas the
      association of systemic illness with musculoskeletal symptoms and numerous viral
      infections is well known, such an association with hepatitis A has only been
      rarely reported. We describe a case of hepatitis A infection mimicking adult
      onset Still's disease, and review the pathogenesis and differential diagnosis of
      Still's disease and the extraarticular manifestations of hepatitis.

PMID- 10914872
TI  - Extosis of rib simulating a solitary pulmonary nodule.

PMID- 10914873
TI  - Multiple dislocations of distal interphalangeal joints associated with
      interstitial pneumonia and Sjogren's syndrome: a possible new complex.

PMID- 10914874
TI  - First international conference on polymyalgia rheumatica and giant cell
      arteritis, Prato, Italy. May 25-26, 1999.

PMID- 10914875
TI  - Polymyalgia rheumatica with low erythrocyte sedimentation rate at diagnosis.

PMID- 10914876
TI  - Why would fibromyalgia patients have osteoporosis?

PMID- 10914877
TI  - Nabumetone induced pseudoporphyria in childhood.

PMID- 10914878
TI  - Rheumatic manifestations in patients with thromboangiitis obliterans (Buerger's
      disease).

PMID- 10914879
TI  - Health status in SLE.

PMID- 10914880
TI  - Lack of correlation between gastric Helicobacter pylori infection and primary or
      secondary Raynaud's phenomenon in patients with systemic sclerosis.

PMID- 10914881
TI  - Impotence in a patient with rheumatoid arthritis treated with methotrexate.

PMID- 10914882
TI  - Osteoporosis--less than expected in patients with scleroderma?

PMID- 10914883
TI  - Reversible polymyositis occurring during psoralen and ultraviolet A (PUVA)
      therapy.

PMID- 10914884
TI  - Cogan's syndrome: a rare vasculitis in childhood.

PMID- 10914885
TI  - Analysis of saliva for periodontal diagnosis--a review.
AB  - BACKGROUND: This review examines salivary constituents as potential diagnostic
      tests for periodontal disease. Saliva is a fluid that is readily available and
      contains locally-produced microbial and host response mediators, as well as
      systemic (serum) markers that may prove to be an aid in the diagnosis of
      periodontal disease. METHODS: A medline search was conducted and the relevant
      literature concerning the applications of saliva for periodontal diagnosis was
      reviewed. RESULTS: Based on the literature, salivary markers that have been
      studied as potential diagnostic tests for periodontal disease include proteins of
      host origin (i.e., enzymes, immunoglobulins), phenotypic markers, host cells,
      hormones (cortisol), bacteria and bacterial products, ions and volatile
      compounds. CONCLUSIONS: A number of markers show promise as sensitive measures of
      disease and the effectiveness of therapy. At this time, host-derived enzymes and
      other inflammatory mediators orginating from the gingival crevice appear to hold
      the greatest promise as salivary diagnostic tests for periodontal disease. Longer
      term longitudinal studies, however, are required to establish the relationship
      between specific markers and progression of periodontal disease. Furthermore,
      analysis of saliva may offer a cost-effective approach to assessment of
      periodontal disease in large populations.

PMID- 10914886
TI  - Treatment of intrabony defects with guided tissue regeneration and enamel-matrix
      proteins. An experimental study in monkeys.
AB  - BACKGROUND: Enamel matrix proteins (EMD) have recently been introduced in
      regenerative periodontal treatment. However, no histological data are yet
      available concerning the effect of treating intrabony periodontal defects with
      EMD, and no histological comparisons have been made comparing the result of
      treatment of intrabony defects with EMD with that of the treatment with guided
      tissue regeneration (GTR). AIM: Therefore, the aim of the present study was to
      evaluate histologically in monkeys the effect of treating intrabony defects with
      EMD, GTR or combined EMD and GTR. METHOD: Intrabony periodontal defects were
      produced surgically at the distal aspect of teeth 14, 11, 21, 24, 34, 31, 41 and
      44 in 3 monkeys (Macaca fascicularis). In order to prevent spontaneous healing
      and to enhance plaque accumulation metal strips were placed into the defects.
      After 6 weeks the defects were exposed using a full-thickness flap procedure. The
      granulation tissue was removed and the root surfaces were debrided by means of
      hand instruments. Subsequently, the defects were treated using one of the
      following therapies: (i) GTR, (ii) EMD, or (iii) combination of EMD and GTR. The
      control defects were treated with coronally repositioned flaps. After 5 months,
      the animals were sacrificed and perfused with 10% buffered formalin for fixation.
      Specimens containing the defects and surrounding tissues were dissected free,
      decalcified in EDTA and embedded in paraffin. 8 microm thick histological
      sections were cut and stained and subsequently examined under the light
      microscope. RESULTS: In the control specimens, the healing was characterized by a
      long junctional epithelium and limited periodontal regeneration (i.e., new
      periodontal ligament, new cementum with inserting connective tissue fibers and
      new bone) in the bottom of the defect. The GTR-treated defects consistently
      presented periodontal regeneration when the membranes were not exposed whereas
      the sites treated only with EMD presented regeneration to a varying extent. The
      combined therapy did not seem to improve the results. CONCLUSION: It can be
      concluded that all 3 treatment modalities favor periodontal regeneration.

PMID- 10914888
TI  - Methodological considerations in the assessment of gingival crevicular fluid
      volume.
AB  - In 4 studies on gingival crevicular fluid volume (GCFV) determination, the
      reliability of measurements, influences of plaque, circadian rhythms and
      stability over 24 h were examined. Samples were taken at 2 sites with a modified
      intracrevicular method. Reliability (n=40): repeated GCFV determinations within 5
      min revealed good reliability coefficients (r(tt)>0.80). Influences of
      supragingival plaque (n=80): repeated GCFV determinations within 5 min with
      plaque removal between measurements in fourty subjects, the other subjects
      serving as control, revealed no group differences with respect to the differences
      between measurements. Circadian rhythms (n=20): GCFV was assessed 6x throughout
      the day. Repeated measures ANOVA revealed no significant time effect. Stability
      over 24 h under constant clinical conditions (n=20): measures were taken at 16:00
      h on 2 consecutive days, several disturbing variables were kept constant. Retest
      correlations revealed a low stability (i.e., high variability) of GCFV measures
      under constant clinical conditions (r(tt)=0.38 for tooth 11 and r(tt)= -0.25 for
      tooth 26). It is concluded that GCFV determination can be done with high
      reliability, the validity of measurements neither being affected by supragingival
      plaque nor by diurnal rhythms. The low stability of measurements questions the
      validity of GCFV for diagnostic purposes.

PMID- 10914887
TI  - Serum IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis
      and healthy subjects.
AB  - BACKGROUND/AIMS: Established periodontal diseases may be associated with antibody
      responses to periodontal pathogens, but it is not known at which stage of disease
      this antibody response is initiated. This study aimed to characterize the host
      systemic response in initial periodontitis, gingivitis, and periodontal health,
      to evaluate whether elevated serum antibodies to subgingival species could be
      detected in initial periodontitis. METHOD: Human systemic immune response were
      evaluated to 40 subgingival bacterial species in 16 healthy, 21 gingivitis, 11
      initial periodontitis and 5 progressing recession adults. Subjects had minimal
      periodontal attachment level (AL) loss at baseline. Disease categories were
      determined after 12 months monitoring at three-month intervals. Increased AL loss
      > or = 1.5 mm (disease activity) at interproximal sites defined initial
      periodontitis, recession was characterized by AL loss at buccal sites. Serum IgG
      antibodies were evaluated semi-quantitatively by immunoblot from blood taken at
      baseline, active and final visits. RESULTS: No antibody was detected from 55% of
      reactions. When detected, levels were below those reported for advanced
      periodontitis subjects. There were no major differences in serum antibody levels
      between healthy, gingivitis and initial periodontitis subjects, despite
      differences in the subgingival microbiota. Serum antibodies for more species were
      detected in recession subjects, compared with the other study subjects. No
      changes in antibody levels were detected between baseline, active, and final
      visits. No systematic association between species colonization and presence of
      systemic antibody was observed. CONCLUSIONS: This study did not detect
      differential elevation of mean serum antibody levels in initial periodontitis
      subjects, suggesting that serum antibody levels are not sensitive risk markers
      for initial periodontitis.

PMID- 10914889
TI  - Fc(alpha) receptor I (CD89) on neutrophils in periodontal lesions.
AB  - AIMS: In this study, we have examined the occurrence of FcalphaRI-bearing cells
      in gingival tissue, gingival fluid and blood, in search for possible roles of IgA
      and FcalphaRI in periodontal lesions. METHODS: Gingival biopsies from inflamed
      and healthy sites were obtained from patients with chronic marginal
      periodontitis. Sections of inflamed gingiva were examined by immunofluorescence
      techniques and compared to sections from healthy sites. Smears were made from
      blood and gingival crevicular fluid and similarly studied. RESULTS: Dense
      infiltrates of neutrophils with strong expression of FcalphaRI (and FcgammaRIII)
      were found in connective tissue and epithelium of the apical part of periodontal
      pockets from diseased sites. In contrast, only few such cells were found in
      healthy gingiva from the same patients. Neutrophils in gingival fluid, tissue and
      blood expressed FcalphaRI with similar intensity, whereas the expression of
      FcgammaRIII was significantly decreased in gingival crevicular fluid.
      Considerable numbers of bacteria from gingival plaque were found to be covered by
      IgA. CONCLUSION: It is suggested that FcalphaRI on neutrophils may play an
      important role in elimination of IgA-opsonized bacteria, both in periodontal
      tissue and the adjacent pockets.

PMID- 10914890
TI  - Effect of 3 dentifrices containing triclosan and various additives. An
      experimental gingivitis study.
AB  - BACKGROUND: The antiplaque and antigingivitis effect of 3 dentifrices was
      evaluated using the 21-day partial-mouth experimental model of gingivitis.
      METHOD: 25 volunteers took part in this cross-over, double-blind study, carried
      out in 4 phases of 21 days each. For each phase of the study, a toothshield of
      the IV quadrant was constructed for each volunteer. 2 antiplaque dentifrices from
      the market, one containing triclosan + pvm/ma and the other triclosan + Zn, were
      compared with an experimental formulation and its placebo. The experimental
      dentifrice contained triclosan + pvm/ma + Zn + PPi and the placebo (control) did
      not contain these substances. The subjects were stratified according to their
      whole-mouth baseline plaque (PI), gingivitis (GI) and bleeding (BI) index scores,
      and then randomly assigned to 1 of 4 dentifrices. During each phase, while the
      volunteers brushed their teeth with one of the dentifrices, the IV quadrant was
      protected by the toothshield filled with the dentifrice used. After each phase,
      dental plaque, gingivitis and bleeding indices were determined. RESULTS: The
      results showed that only the formulation containing triclosan + pvm/ma + Zn + PPi
      was able to reduce PI (28.8%), GI (35.9%) and BI (30.4%) in comparison with
      controls (p<0.05). CONCLUSIONS: The data suggest that a dentifrice containing the
      combination of triclosan + pvm/ma + Zn + PPi should be formulated for dental
      plaque control.

PMID- 10914891
TI  - Carboxypeptidase-mediated metabolism of calcitonin gene-related peptide in human
      gingival crevicular fluid--a role in periodontal inflammation?
AB  - BACKGROUND: Metabolism by peptidases plays an important role in modulating the
      levels of biologically-active neuropeptides. The metabolism of the anti
      inflammatory neuropeptide calcitonin gene-related peptide (GCRP), but not the pro
      inflammatory neuropeptides substance P (SP) and neurokinin A (NKA) by components
      of the gingival crevicular fluid (GCF), could potentiate the inflammatory process
      in periodontitis. AIMS: To characterise the extracellular hydrolysis of CGRP as a
      mechanism for the selective inactivation of this neuropeptide in GCF from
      periodontitis sites. METHODS: Samples of GCF from periodontitis patients and
      periodontally-healthy subjects were incubated with synthetic human SP, NKA or
      CGRP. Reaction between the GCF constituents and synthetic peptides was allowed to
      progress from 0-180 min. Results of neuropeptide metabolism at each time were
      analysed by matrix-assisted laser desorption/ionisation mass spectrometry.
      RESULTS: There was no evidence of metabolism of SP, NKA or CGRP by constituents
      of healthy GCF. Metabolism of synthetic SP and NKA was minimal even after
      extensive incubation with periodontitis GCF. However, loss of carboxy-terminal
      amino acids was evident after only 1 min incubation with periodontitis GCF. The
      pattern of CGRP metabolism, which proceeded from the C-terminus, indicated that
      the neuropeptide was degraded by a carboxypeptidase. After 180 min, there was
      extensive carboxypeptidase degradation of CGRP to an 11 amino acid peptide.
      CONCLUSIONS: It is concluded that carboxypeptidase activity in GCF from
      periodontitis patients is responsible for rapid breakdown of CGRP but not SP or
      NKA. The rapid action of this carboxypeptidase on the anti-inflammatory
      neuropeptide CGRP is suggestive of a pathophysiological role for the enzyme in
      selectively degrading CGRP, thereby potentiating periodontal inflammation.

PMID- 10914892
TI  - Factors influencing phenytoin-induced gingival enlargement.
AB  - AIM: To ascertain the prevalence and severity of phenytoin-induced gingival
      enlargement (PIGE) as well as the relationship between PIGE and risk factors.
      METHOD: An outpatient population of patients on phenytoin treatment and attending
      the epilepsy clinic at Prince Mshiyeni Memorial Hospital (PMMH) in Durban, South
      Africa, was requested to participate. A structured questionnaire was used to
      collect data on patients' demographics, social habits (e.g., drinking and
      smoking), dental and oral hygiene practices and medication history. Gingival
      enlargement, dental plaque and gingival bleeding was also measured to assess
      gingival health. Venous blood was collected for serum folate and phenytoin serum
      levels measurements. A regression analyses was then undertaken to ascertain the
      association between PIGE and the risk factors. Factors tested for correlation
      were serum phenytoin and folate levels, age, bacterial plaque, gingival
      inflammation, toothbrushing, smoking and alcohol consumption. The association
      between PIGE and the risk factors was assessed either individually, i.e., as a
      single entity or in combination--multifactorially. RESULTS: Of the 134 patients
      studied, 62% had PIGE scores > or = 1, while 8% had a PIGE score of zero. With
      the exception of plaque, which showed a moderate association with PIGE (r=0.4),
      no other factor on its own was statistically significantly related to PIGE. In
      the multiple linear regression analysis, factors which on their own did not have
      a strong influence became more important. Bacterial plaque (p=0.0001), younger
      age (p=0.01) and higher free serum phenytoin levels (p= 0.03), were associated
      with PIGE. Although known to be associated with periodontal diseases, smoking and
      alcohol, (p=0.03 and p=0.04 respectively), appeared to give some protection
      against PIGE. CONCLUSION: Risk factors associated with PIGE may have a
      synergistic effect. Bacterial plaque, however, appears the most important
      determinant of PIGE severity. This latter finding emphasises the importance of
      instituting a preventive plaque-control programme, particularly in young patients
      on phenytoin therapy.

PMID- 10914893
TI  - Reduced numbers of Langerhans cells and increased HLA-DR expression in
      keratinocytes in the oral gingival epithelium of HIV-infected patients with
      periodontitis.
AB  - BACKGROUND: HIV-seropositive (HIV+) patients become increasingly susceptible to
      periodontal diseases as HIV infection proceeds. We have previously shown that
      HIV+ patients with chronic marginal periodontitis (CMP) have remarkably increased
      numbers of gingival plasma cells in the connective tissue underlying the oral
      gingival epithelium, but depressed specific serum IgG levels towards
      periodontopathogenic bacteria. Langerhans cells (LC) and keratinocytes (KC) are
      antigen-presenting cells that are important in promoting immune responses.
      METHOD: In this study we examined, by means of immunofluorescence, the
      distribution and numbers of LC and activated KC in biopsies taken from inflamed
      periodontal sites in HIV+ and HIV patients with CMP. RESULTS: In the pocket
      epithelium in both patient groups, basal layer KC expressed HLA-DR molecules. In
      the oral gingival epithelium of HIV+ patients, basal layer KC also expressed HLA
      DR molecules and numbers of LC were decreased as compared with HIV persons.
      CONCLUSION: The findings suggest that the oral gingiva in HIV+ patients may be
      affected by inflammation.

PMID- 10914894
TI  - Beta-lactamase producing bacteria in the subgingival microflora of adult patients
      with periodontitis. A comparison between Spain and The Netherlands.
AB  - BACKGROUND/AIMS: Countries with a high per capita antibiotic use frequently
      demonstrate a high level of drug resistance. The aim of this study was to compare
      the prevalence and levels of beta-lactamase producing bacteria in the subgingival
      microflora in adult patients with periodontitis in Spain and The Netherlands, and
      to characterise beta-lactamase producing bacteria in both patient samples.
      METHOD: Patients with moderate to severe periodontitis were consecutively
      selected and asked to report on: current systemic disorders and medications,
      history of use of antibiotics, and smoking habits. Clinical variables included
      probing pocket depth, clinical attachment level, plaque, bleeding on probing, and
      suppuration. Pooled subgingival samples of 4 selected sites were anaerobically
      cultured in blood agar plates with and without amoxicillin, and
      amoxicillin/clavulanate. Bacterial colonies growing on amoxicillin plates but not
      on amoxicillin/clavulanate plates were tested for beta-lactamase production. beta
      lactamase producing bacteria were isolated and identified. RESULTS: 31 patients
      were studied in the Spanish group and 30 in the Dutch group. Comparable mean
      gender and ages were found. Evaluation of previous antibiotic use revealed that,
      in the previous 12 months, 54.8% of patients in the Spanish group and 10% in the
      Dutch group reported antibiotic use (p<0.001). The prevalence of beta-lactamase
      producing bacteria was 87.1% in the Spanish group and 73.3% in the Dutch group.
      Total counts of beta-lactamase producing bacteria on amoxicillin plates (p<0.01),
      the mean number of different beta-lactamase producing colonies per patient
      (p<0.001), and the number of amoxicillin resistant colonies (p<0.001) were
      significantly higher in the Spanish group. 74 beta-lactamase producing strains in
      the Spanish group and 33 in the Dutch group were isolated for identification. 23
      out of 35 identified strains in the Spanish group, and 32 out of 33 in the Dutch
      group belonged to Prevotella genus. CONCLUSIONS: A high prevalence of beta
      lactamase producing bacteria has been evaluated in two distinct populations,
      belonging to two European countries with clear differences in antibiotic usage
      policy. A higher prevalence and a more complex beta-lactamase producing
      microflora, were found in the Spanish group, associated with a higher antibiotic
      consumption. This study shows that a higher use of beta-lactam antibiotics is
      reflected in the % of beta-lactamase producing bacteria in the subgingival
      microflora of patients with periodontitis. This information may be important in
      the treatment of severe periodontitis.

PMID- 10914895
TI  - Changes in substance P and neurokinin A in gingival crevicular fluid in response
      to periodontal treatment.
AB  - BACKGROUND: The study of periodontitis provides a unique model for assessing the
      involvement of neuropeptides in inflammatory disease. AIM: To investigate the
      effects of periodontal treatment, resulting in a return to periodontal health, on
      the levels of substance P (SP) and neurokinin A (NKA) in gingival crevicular
      fluid (GCF). METHOD: We completed a cause of non-surgical treatment for 8
      subjects with periodontitis (6 females 2 males, mean age 45.1, range 38-67 years)
      started a course of non-surgical periodontal treatment. Clinical indices were
      measured at 2 periodontitis sites at the initial visit and at 8 weeks after the
      completion of treatment in each subject. A 30-s sample of GCF was collected from
      each test site using perio paper strips. Each strip was placed into 500 microl of
      ice cold 0.1 M PBS, pH 7.4, vortex mixed for 30 s, and then stored at -70 degrees
      C until analysed by radioimmunoassay. RESULTS: The clinical condition of all test
      sites improved as a result of the periodontal treatment. The levels (pg/30 s
      sample) of SP fell from 56.3 (SD 66.0) at the initial visit to 4.2 (3.1) after
      treatment, p=0.017. The concentration (pg/microl) of SP in GCF fell from 140.6
      (175.6) to 24.2 (11.1), p=0.036. The levels of NKA fell from 30.5 (17.1) to 10.6
      (4.9), p=0.012 whereas the concentration changed little from 85.4 (43.5) to 61.6
      (15.1), p=0.41. CONCLUSION: The reduction in inflammation resulting from
      effective periodontal treatment is associated with a reduction in the levels of
      tachykinins in gingival crevicular fluid.

PMID- 10914896
TI  - Actinobacillus actinomycetemcomitans-associated peri-implantitis in an edentulous
      patient. A case report.
AB  - BACKGROUND: Peri-implantitis is a risk factor for implant loss. Late bacterial
      infection of the peri-implant tissues and loss of alveolar bone in edentulous
      patients is caused by commensal oral anaerobic bacteria. In partially edentulous
      patients, Porphyromonas gingivalis and occasionally Actinobacillus
      actinomycetemcomitans are associated with peri-implantitis lesions. AIMS: To
      investigate the microbiology of a peri-implantitis case in an edentulous patient.
      METHODS: Anaerobic culture techniques and selective culture techniques for A.
      actinomycetemcomitans were used to study the peri-implant microflora at sites
      with and without bone loss. RESULTS: An anaerobic peri-implant microflora with
      several putative periodontal pathogens was found at sites with bone loss.
      Furthermore, a metronidazole-resistant A. actinomycetemcomitans was isolated. The
      A. actinomycetemcomitans infection did not respond to systemic doxycycline
      therapy, despite good susceptibility in vitro. CONCLUSIONS: The present case of
      severe A. actinomycetemcomitans-associated peri-implantitis shows the importance
      of pre-operative infection control. The findings in this case show that remaining
      teeth affected by periodontitis can be a serious risk factor for peri
      implantitis.

PMID- 10914897
TI  - SNM 2000 Annual Meeting: fusion is the theme as nuclear medicine enters the new
      century.

PMID- 10914898
TI  - PubMed Central: the JNM perspective.

PMID- 10914899
TI  - Randomized controlled trials are not appropriate for imaging technology
      evaluation.

PMID- 10914901
TI  - Pharmacokinetics and metabolism of 123I-BMIPP fatty acid analog in healthy and
      CD36-deficient subjects.
AB  - Some have suggested that CD36, which is a multifunctional receptor with a
      molecular weight of 88 kDa, functions as a long-chain fatty acid (LCFA)
      transporter. We recently reported on a complete myocardial accumulation defect of
      the radiolabeled LCFA analog (123)I-15-(p-iodophenyl)-(R,S)-methylpentadecanoic
      acid (BMIPP) in patients with CD36 deficiency. In this study, we investigated the
      pharmacokinetics of BMIPP in patients with a myocardial accumulation defect of
      BMIPP accompanied by CD36 deficiency. METHODS: Five patients (3 men, 2 women)
      with CD36 deficiency and 3 healthy men were investigated. Serial myocardial
      images were obtained every 70 s for 20 min (dynamic acquisition) and at 30, 60,
      120, 180, and 240 min (static acquisition) after an intravenous bolus injection
      of 148 MBq BMIPP. Whole-body imaging was performed 60 min after injection. Plasma
      levels of BMIPP and its final metabolite, piodophenylacetic acid, at 2, 5, 10,
      30, 60, 120, and 240 min after administration were determined. RESULTS: In the
      CD36-deficient patients, myocardial images could not be obtained for up to 240
      min after administration, and cardiac pool images showing only the cardiac
      chambers were obtained. The heart-to-mediastinum ratio was significantly lower in
      the CD36-deficient patients than in the healthy volunteers (1.71 +/- 0.11 versus
      2.95 +/- 0.22, P < 0.05). Hepatic uptake of BMIPP was nearly double in CD36
      deficient patients. The elimination of BMIPP from the circulation was retarded in
      the CD36-deficient patients. CONCLUSION: We suggest that CD36 deficiency leads to
      decreased myocardial accumulation of BMIPP and retardation of BMIPP elimination
      from the circulation. The accumulation defect is probably caused by a defect in
      LCFA uptake into the myocardium through CD36.

PMID- 10914900
TI  - Correlation between severity of pulmonary arterial hypertension and 123I
      metaiodobenzylguanidine left ventricular imaging.
AB  - It remains unclear whether cardiac sympathetic nervous function is disturbed in
      patients with pulmonary arterial hypertension (PH) and how sympathetic
      dysfunction is related to PH. METHODS: In this study, (123)I
      metaiodobenzylguanidine (MIBG) imaging of the heart, which reveals the
      sympathetic innervation of the left ventricle, was performed in 7 healthy
      volunteers without cardiopulmonary disease (control subjects); 55 patients with
      PH, including 27 with chronic thromboembolic pulmonary hypertension (CTEPH) of
      major vessels; and 28 patients with primary pulmonary hypertension (PPH).
      RESULTS: Cardiac (123)I-MIBG uptake, assessed as the heart-to-mediastinum
      activity ratio (H/M), was significantly lower in the CTEPH and PPH groups
      compared with that in the control group (P < 0.01). Myocardial MIBG turnover,
      expressed as the washout rate (WR [%]) from 15 to 240 min, was significantly
      higher in the CTEPH and PPH groups than that in the control group (P < 0.01). In
      the PPH group, H/M and WR values of MIBG correlated with the severity of
      pulmonary hypertension (represented by total pulmonary vascular resistance
      determined by right heart catheterization), the right ventricular ejection
      fraction determined by electron beam CT, and other variables but did not
      correlate well in the CTEPH group. In both groups, patients with H/M > or = 2.0
      showed better cumulative survival than did those with H/M < 2.0 (P < 0.05).
      CONCLUSION: Patients with PH have significant left ventricular myocardial
      sympathetic nervous alteration. (123)I-MIBG imaging of the heart is useful for
      assessing the severity of pulmonary hypertension caused by PPH or CTEPH.

PMID- 10914902
TI  - Improved uniformity in tomographic myocardial perfusion imaging with attenuation
      correction and enhanced acquisition and processing.
AB  - Tissue attenuation results in nonuniform myocardial perfusion images with
      significant sex differences. New SPECT imaging protocols to correct attenuation
      are currently under investigation. This study was performed to assess the effects
      of attenuation correction (AC) on overall image uniformity compared with more
      conventional imaging protocols in both men and women. METHODS: Thirty-nine
      patients (19 men, 20 women) with less than a 5% likelihood of coronary artery
      disease were studied. (99m)Tc-sestamibi studies were acquired with a triple-head
      scanner equipped with a simultaneous transmission and emission protocol. Four
      imaging protocols were compared: a 180 degrees acquisition and filtered
      backprojection reconstruction (FBP), a 360 degrees acquisition and FBP, a 360
      degrees acquisition and iterative reconstruction (IT), and a 360 degrees
      acquisition with IT and AC. Quantitative analysis was performed to evaluate
      myocardial tracer uniformity for men and women. RESULTS: 180 degrees, 360 degrees
      FBP, and 360 degrees IT showed sex differences, with decreased tracer
      concentration in the anterior wall in women and decreased tracer concentration in
      the inferior wall in men. AC images showed the greatest uniformity (9.9%
      coefficient of variation for AC versus 12.5% for IT, P < 0.0001), and no
      statistically significant differences in uniformity were seen between male and
      female AC studies. CONCLUSION: More uniform myocardial perfusion images were
      obtained with AC, resulting in images with no differences in uniformity between
      men and women. These techniques are expected to improve specificity and overall
      diagnostic accuracy.

PMID- 10914903
TI  - Vagus nerve stimulation in refractory epilepsy: SPECT activation study.
AB  - Left-sided vagus nerve stimulation (VNS) is an efficacious treatment for patients
      with refractory epilepsy. The exact mechanism of action remains to be elucidated.
      This study investigated the acute effects of initial VNS in patients with
      refractory complex partial epilepsy with or without secondary generalization
      (complex partial seizures [CPS] +/- SG) by means of a perfusion activation study
      with SPECT. METHODS: Twelve patients (mean age, 32.2 +/- 10.2 y; age range, 12-47
      y) with a mean duration of CPS +/- SG of 19.8 +/- 10.0 y (range, 5-33 y) received
      VNS. All patients were considered unsuitable candidates for resective surgery
      because of nonlocalizing findings on presurgical evaluation. VNS efficacy was
      evaluated for patients with at least 4-mo follow-up. VNS-induced regional
      cerebral blood flow alterations were studied by a (99m)Tc-ethyl cysteinate dimer
      activation study with a single-day split-dose protocol before and immediately
      after an initial stimulation. Images were acquired on a triple-head camera with
      fanbeam collimators. After coregistration to a standardized template, both a
      semiquantitative analysis using predefined volumes of interest and a voxel-by
      voxel analysis of the intrasubject activation (statistical parametric mapping)
      were performed. RESULTS: Seizure-frequency changes ranged from 100% decrease to
      0% after VNS. The semiquantitative analysis revealed a consistent decrease of
      activity in the left thalamus (ratio stimulator on/off = 0.94 +/- 0.04; P =
      0.005). These results were concordant with the voxel-by-voxel analysis in which a
      significant deactivation in the left thalamus was found with spread to the
      ipsilateral hippocampus. There was no statistically significant correlation
      between initial VNS-induced thalamic hypoperfusion and seizure reduction at
      maximum follow-up. CONCLUSION: Our findings are consistent with the hypothesis
      that acute VNS reduces seizure onset or propagation through inhibition of the
      thalamic relay center. Differences with limited H2(15)O PET data may be
      associated with temporal effects caused by a stimulation-induced local
      hemodynamic response and need further investigation. SPECT allows study of
      cerebral physiopathologic effects of vagus nerve electrostimulation in complex
      partial epilepsy.

PMID- 10914904
TI  - Longitudinal evaluation of early Alzheimer's disease using brain perfusion SPECT.
AB  - The aim of this SPECT study was to determine the initial abnormality and
      longitudinal changes in regional cerebral blood flow (rCBF) in early Alzheimer's
      disease (AD) using statistical parametric mapping (SPM). METHODS: rCBF was
      noninvasively measured using (99m)Tc-ethyl cysteinate dimer SPECT in 32 patients
      complaining of mild cognitive impairment, with a Mini-Mental State Examination
      score more than 24 at the initial study, and 45 age-matched healthy volunteers.
      All patients satisfied the diagnostic criteria of AD during the follow-up period
      of at least 2 y. Follow-up SPECT studies were performed on the patients at a mean
      interval of 15 mo. We used the raw data (absolute rCBF parametric maps) and the
      adjusted rCBF images of relative flow distribution (normalization of global
      cerebral blood flow [CBF] for each subject to 50 mL/100 g/min with proportional
      scaling) to compare these groups with SPM. RESULTS: In the baseline study, the
      adjusted rCBF was significantly and bilaterally decreased in the posterior
      cingulate gyri and precunei of patients compared with healthy volunteers. In the
      follow-up study, selected reduction of the adjusted rCBF was observed in the left
      hippocampus and parahippocampal gyrus. These areas showed the most prominent
      reduction in absolute rCBF on each occasion. Moreover, further decline of the
      absolute rCBF was longitudinally observed in extensive areas of the cerebral
      association cortex. CONCLUSION: SPM analysis showed the characteristic early-AD
      rCBF pattern of selective decrease and longitudinal decline, which may be
      overlooked by a conventional region-of-interest technique with observer a priori
      choice and hypothesis. This alteration in rCBF may closely relate to the
      pathophysiologic process of this disease.

PMID- 10914905
TI  - Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in
      visualization of suppressed thyroid tissue.
AB  - Both (201)TI and (99m)Tc-methoxyisobutyl isonitrile (MIBI) have been used in the
      visualization of suppressed thyroid tissue in patients with autonomously
      functioning thyroid nodules (AFTNs). It has been suggested that thyroid
      stimulating hormone (TSH) control is not a major determinant of both tracers.
      However, the mechanism of thyroid uptake of these agents is controversial. In
      this study, we compared (201)TI and MIBI in the visualization of suppressed
      thyroid tissue in patients with a solitary toxic AFTN. METHODS: Thirty-two
      patients (13 triiodothyronine [T3] and 19 T3 + levorotatory thyroxine [T4]
      hyperthyroid patients) with toxic AFTNs visualized on (99m)Tc-pertechnetate
      scanning were included in the study. All patients underwent MIBI and (201)TI
      thyroid scintigraphy within a 3-d interval. The scintigrams were analyzed both
      visually and semiquantitatively. For the semiquantitative analysis, regions of
      interest (ROIs) were generated over the nodule (N) and contralateral normal lobe
      (E), and the mean counts in each ROI were calculated. RESULTS: The N/E uptakes
      (mean +/- SD) for pertechnetate, MIBI, and (201)TI were 11.37 +/- 4.53, 4.76 +/-
      1.38, and 1.63 +/- 0.15, respectively, in T3 + T4 hyperthyroid patients and 9.46
      +/- 3.64, 2.73 +/- 0.63, and 1.57 +/- 0.23, respectively, in T3 hyperthyroid
      patients. Our results showed that (201)TI uptake of suppressed thyroid tissue
      compared with AFTN was more prominent and significantly higher than that of MIBI
      for both groups of patients (P = 1.08E-05 for T3 and 6.15E-09 for T3 + T4
      hyperthyroidism). There was no significant difference for either pertechnetate or
      (201)TI (P > 0.05) when the N/E uptakes of both groups of patients were compared.
      However, the N/E uptake of MIBI in T3 + T4 hyperthyroid patients was
      significantly higher than that in T3 hyperthyroid patients (P = 6.69E-06).
      CONCLUSION: Clear visualization of suppressed thyroid tissue with both (201)TI
      and MIBI in patients with low serum concentrations of TSH suggests that TSH is
      not a major factor in the thyroid uptake of either agent. (201)TI is superior to
      MIBI in the visualization of suppressed thyroid tissue in patients with a toxic
      thyroid nodule. An increased rate of metabolism in the follicular cells of AFTNs
      in T3 + T4 hyperthyroid patients compared with that in T3 hyperthyroid patients
      might be responsible for the higher N/E for MIBI compared with that for (201)TI.

PMID- 10914906
TI  - Radioimmunotherapy with intravenously administered 131I-labeled chimeric
      monoclonal antibody MOv18 in patients with ovarian cancer.
AB  - We investigated the safety and pharmacokinetics of (131)I-labeled chimeric
      monoclonal antibody MOv18 ((131)I-c-MOv18 IgG) in patients with ovarian cancer
      and the estimated radiation dose to cancer-free organs and tumor. METHODS: Three
      patients were injected intravenously with 3 GBq (131)I-c-MOv18. Toxicity was
      evaluated according to the World Health Organization toxicity scales. Blood
      sampling was performed for 12 wk after injection. Whole-body and SPECT imaging
      was performed frequently. Dose rates were obtained with a portable dose-rate
      measure. Quantitative activity analysis of several organs was performed with the
      region-of-interest technique. Absorbed doses were calculated using MIRDOSE3.
      RESULTS: Transient changes in hematologic profiles were seen in 2 patients.
      Pancytopenia developed in 1 patient; on analysis, she entered the study probably
      with exhausted bone marrow reserves. Nonhematologic toxicity was mild. No human
      antichimeric antibody responses were observed. Mean isolation time was 12 d. The
      plasma elimination half-life increased almost 3-fold compared with that after
      tracer doses of c-MOv18. Dosimetry showed mean absorbed doses of 163, 380, 276,
      338, 781, and 216 cGy, for whole-body, liver, kidney, spleen, lung, and red
      marrow, respectively. Tumor-absorbed doses ranged from 600 to 3800 cGy. All
      patients achieved a stable disease state, as confirmed by CT and carcinoma
      associated antigen CA 125, lasting from 2 to >6 mo. CONCLUSION: (131)I-labeled c
      MOv18 can safely be given to patients with noncompromised bone marrow reserves
      and may have therapeutic potential particularly in patients with minimal residual
      disease.

PMID- 10914907
TI  - A meta-analysis of the literature for whole-body FDG PET detection of recurrent
      colorectal cancer.
AB  - A meta-analysis of the literature for the use of FDG PET in the detection of
      recurrent colorectal cancer (CRC) was conducted to evaluate the quality of the
      reported studies. Overall values for the sensitivity and specificity of whole
      body FDG PET and an overall FDG PET-directed percentage change in management were
      also determined through this analysis. METHODS: Guidelines to evaluate the
      articles were formulated on the basis of the U.S. medical payer source criteria
      for assessing studies that report information on usage of new medical technology.
      A metaanalysis was conducted using methodology described in the peer-reviewed
      literature. RESULTS: On the basis of the guidelines established for our review,
      the availability of necessary information for assessing the reliability of the
      FDG PET data for diagnosing recurrent CRC was less than ideal. Through a meta
      analysis of 11 articles, we determined, within a 95% confidence level, an overall
      sensitivity of 97% (95% confidence level, 95%-99%) and an overall specificity of
      76% (95% confidence level, 64%-88%) for FDG PET detecting recurrent CRC
      throughout the whole body. Furthermore, through pooling of the change-in
      management data, an overall FDG PET-directed change in management was calculated
      to be 29% (95% confidence level, 25%-34%). CONCLUSION: Our review suggests that
      improvements can be made to more effectively report the results of these FDG PET
      studies. The overall values determined through the meta-analysis indicate the
      potential benefits of using FDG PET as a diagnostic or management tool.
      Furthermore, these values should prove to be useful to assess the cost
      effectiveness of using FDG PET in the management of patients with recurrent CRC.

PMID- 10914908
TI  - Postexercise lung uptake of 99mTc-sestamibi determined by a new automatic
      technique: validation and application in detection of severe and extensive
      coronary artery disease and reduced left ventricular function.
AB  - This study validated a new automatic algorithm for assessment of lung-to-heart
      ratio (L/H) of radiotracers in myocardial perfusion SPECT and assessed the
      diagnostic value of (99m)Tc-sestamibi L/H after exercise. METHODS: The new
      technique extracts a left ventricular region of interest (ROI) from a summed
      anterior projection image and generates a lung ROI by reshaping and translating
      the left ventricular ROI. This algorithm was applied to 230 patients who
      underwent exercise (99m)Tc-sestamibi SPECT (gated SPECT, n = 88) with first-pass
      ventriculography. Normal values were established in 26 patients in whom the
      likelihood of coronary artery disease (CAD) was 5% or less. An abnormality
      threshold for detecting severe and extensive CAD was defined in a subgroup of 109
      patients who underwent coronary angiography and was validated in a prospective
      group (n = 72). RESULTS: The success rate of the automatic algorithm was 97%.
      Excellent correlation was found between automatic and manual L/H values (r =
      0.95; P < 0.001). The mean L/H was higher in patients with a peak exercise
      ejection fraction (EF) less than 40% versus 40% or more (0.51 +/- 0.07 versus
      0.43 +/- 0.05, P < 0.001) and in patients with a poststress EF less than 40%
      versus 40% or more (0.50 +/- 0.07 versus 0.44 +/- 0.06, P < 0.01). A threshold of
      L/H greater than 0.44 yielded a sensitivity and specificity of 63% and 81%,
      respectively, for identifying severe and extensive CAD in the prospective group
      and a sensitivity of 86% in identifying stenosis of 90% or more in the proximal
      left anterior descending artery. CONCLUSION: The new automatic algorithm for
      assessing L/H correlated well with manually derived L/H for (99m)Tc-sestamibi as
      well as (201)TI SPECT. An increased postexercise (99m)Tc-sestamibi L/H adds
      significant diagnostic value to study myocardial perfusion SPECT as a marker of
      severe and extensive CAD and reduced ventricular function.

PMID- 10914909
TI  - Absence of thyroid stunning after diagnostic whole-body scanning with 185 MBq
      131I.
AB  - There has been recent controversy regarding the optimal protocol for imaging and
      ablation of post-thyroidectomy patients. Several authors have suggested that a
      scanning dose of 185-370 MBq (5-10 mCi) (131)I may be capable of producing a
      stunning effect on thyroid tissue that may interfere with the uptake and efficacy
      of the subsequent ablation dose of radioiodine. The purpose of this study was to
      determine whether a 185-MBq (5 mCi) diagnostic dose of (131)I produces a visually
      apparent stunning effect 72 h before (131)I ablation therapy. METHODS: One
      hundred twenty-two consecutive post-thyroidectomy patients for differentiated
      thyroid carcinoma received a 185-MBq (5 mCi) diagnostic dose of (131)I followed
      by a whole-body diagnostic scan at 72 h. On the same day the diagnostic scan was
      completed, the patient was admitted to the hospital and received an (131)I
      ablation therapy dose of 5550 MBq (150 mCi) in most cases. A postablation, whole
      body scan was obtained at 72 h and compared with the previous diagnostic scan for
      any visual evidence of stunning. RESULTS: No cases of visually apparent thyroid
      stunning were observed on any of the postablation scans with regard to the number
      of (131)I foci identified or the relative intensity of (131)I uptake seen.
      CONCLUSION: Diagnostic whole-body scanning can be performed effectively with a
      185-MBq (5 mCi) dose of (131)I 72 h before radioiodine ablation without concern
      for thyroid stunning.

PMID- 10914910
TI  - Captopril-induced changes in MAG3 clearance in patients with renal arterial
      stenosis and the effect of renal angioplasty.
AB  - Angiotensin-converting enzyme inhibition by captopril decreases renal (131)I-o
      iodohippurate sodium or iothalamate extraction in patients with renal artery
      stenosis (RAS). This study investigated the effect of captopril on another renal
      radiopharmaceutical, (99m)Tc-mercaptoacetyltriglycine (MAG3), in particular its
      plasma clearance. METHODS: Three groups of patients were studied. Group I
      contained 22 patients with hypertension but a low likelihood of RAS according to
      negative captopril renography results, confirmed by angiography in 5. Group II
      contained 22 hypertensive patients with RAS documented by angiography and
      positive captopril and plasma renin response. Group III contained 10 patients
      after successful percutaneous transluminal renal angioplasty (PTRA) with negative
      captopril renography results. The 60-min, single-sample technique was used for
      measurement of the plasma clearance of MAG3 during baseline and captopril
      renography. RESULTS: In 18 of 22 group I patients, clearance increased (P < 0.01)
      during captopril renography compared with baseline conditions, whereas in 18 of
      22 group II patients, clearance decreased (P< 0.01). In group III patients,
      clearance was not significantly altered. The clearance decrease in group II did
      not correlate with the blood pressure decrease or plasma renin activity increase
      during captopril renography. CONCLUSION: Renal function assessed by MAG3 plasma
      clearance decreases in hypertensive patients with RAS but increases in patients
      without RAS. MAG3 clearance measurements during baseline and captopril renography
      can thus serve as additional diagnostic information when investigating patients
      with hypertension for the possibility of an RAS.

PMID- 10914911
TI  - The significance of functioning gallbladder visualization on hepatobiliary
      scintigraphy in infants with persistent jaundice.
AB  - The purpose of this study was to determine whether gallbladder visualization can
      help exclude biliary atresia in hepatobiliary scintigraphic studies of infants
      with persistent jaundice. METHODS: One hundred fifty-two infants with persistent
      jaundice (49 patients with a final diagnosis of biliary atresia and 103 with
      biliary patency) were studied using both hepatobiliary scintigraphy and abdominal
      sonography. Food was withheld for 4 h before the examination, and the infants
      were fed nothing but glucose until 6 h after the initial injection of (99m)Tc
      disofenin or until the gallbladder was seen. If the gallbladder was seen, the
      infants were fed milk, and imaging was continued to observe gallbladder
      contractility. RESULTS: In none of the 49 patients with biliary atresia could the
      gallbladder be seen with hepatobiliary scintigraphy, but abdominal sonography
      revealed 9 normal-sized gallbladders. Of the 103 patients with biliary patency,
      hepatobiliary scintigraphy detected the gallbladder more frequently (74%, 76/103)
      than did abdominal sonography (63%, 65/103). All visualized gallbladders
      contracted after the infants were fed milk. If we include visualization of both
      the gallbladder and bowel radioactivity as criteria, the specificity of biliary
      atresia on hepatobiliary scintigraphy increases to 86% (89/103). CONCLUSION:
      Gallbladders were usually visible on hepatobiliary scintigraphy of fasting
      patients with biliary patency. A functioning gallbladder, with or without
      visualization of bowel radioactivity, indicated biliary patency.

PMID- 10914912
TI  - Acute thromboscintigraphy with (99m)Tc-apcitide: results of the phase 3
      multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast
      venography for imaging acute DVT. Multicenter Trial Investigators.
AB  - (99m)Tc-apcitide (formerly known as (99m)Tc-P280) is a radiolabeled peptide that
      binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors
      expressed on the activated platelets that are involved in acute thrombosis. The
      purpose of the phase 3 multicenter clinical trials was to compare (99m)Tc
      apcitide scintigraphy with contrast venography for imaging acute deep venous
      thrombosis (DVT). METHODS: A total of 280 patients were enrolled in 2 clinical
      trials conducted in North America and Europe. Patients were to be within 10 d of
      onset of signs and symptoms of acute DVT or within 10 d of surgery associated
      with a high risk of DVT. (99m)Tc-apcitide scintigraphy and contrast venography
      were to be performed within 36 h. Planar scintigraphic images were obtained at
      10, 60, and 120-180 min after injection. (99m)Tc-apcitide scintigrams and
      contrast venograms were read with masking and also by the institutional
      investigators. RESULTS: Of a total of 243 patients who were evaluable, 61.7% were
      receiving heparin at the time of imaging. Masked reading of (99m)Tc-apcitide
      scintigraphy, compared with masked reading of contrast venography, had a
      sensitivity, specificity, and agreement of 73.4%, 67.5%, and 69.1%, respectively,
      which met the prospectively defined target efficacy endpoint in both trials.
      Institutional reading of (99m)Tc-apcitide scintigraphy, compared with
      institutional reading of contrast venography, had a sensitivity, specificity, and
      agreement of 75.5%, 72.8%, and 74.0%, respectively. However, the entire trial
      population included patients with a history of DVT who may have had old, nonacute
      venous thrombi that could confound the venography results. Therefore, data from
      patients having no history of DVT or pulmonary embolism and who presented within
      3 d of onset of signs and symptoms (n = 63), i.e., patients for whom a venogram
      would be expected to be positive only if acute DVT were present, also were
      analyzed as a subset. In these patients, institutional reading of (99m)Tc
      apcitide scintigraphy, compared with institutional reading of contrast
      venography, had a sensitivity, specificity, and agreement of 90.6%, 83.9%, and
      87.3%, respectively. CONCLUSION: (99m)Tc-apcitide scintigraphy is a new
      diagnostic modality that is highly sensitive for imaging acute DVT.

PMID- 10914913
TI  - Diagnosing deep venous thrombosis: dawn of a new era?

PMID- 10914914
TI  - Myocardial blood flow, function, and metabolism in repetitive stunning.
AB  - Myocardial hibernation refers to a state of persistent left ventricular
      dysfunction resulting from a chronically reduced blood flow, which is improved or
      reversed with revascularization. Increased glucose uptake in areas with reduced
      blood flow at rest on PET has been used successfully to diagnose hibernating
      myocardium. However, hibernation may represent persistent myocardial stunning
      resulting from repeated episodes of ischemia and reperfusion rather than from
      chronic underperfusion. We sought to determine the inter-relationship between
      blood flow, metabolism, and function in a canine model of repetitive myocardial
      stunning. METHODS: Ten dogs underwent 4 sequential 5-min intervals of balloon
      occlusion of the anterior descending or circumflex arteries, each separated by 5
      min of reperfusion. Regional blood flow, metabolism, and function were evaluated
      3-4 h after reperfusion in all dogs and 24 h and 1 wk after reperfusion in 5
      dogs. Regional wall motion was evaluated with echocardiography. Regional blood
      flow was assessed with radioactive microspheres and by [(13)N]ammonia and PET.
      Measurements of oxidative metabolism and glucose uptake (during hyperinsulinemic
      euglycemic clamping) were derived with [(11)C]-acetate, FDG, and PET. RESULTS:
      Regional wall motion was severely decreased after the 4 cycles of ischemia,
      remained impaired 24 h after reperfusion, and normalized after 1 wk. During
      reflow, blood flow in stunned regions was restored to near-normal levels (0.89 +/
      0.07 versus 0.95 +/- 0.07 mL/g/min, P = 0.023). However, glucose uptake in
      stunned regions was significantly decreased at 4 h (73% +/- 5% of remote, P <
      0.001), remained depressed after 24 h of reflow (83% +/- 4% of remote, P =
      0.013), and fully recovered at 1 wk (101% +/- 10% of remote, P = 0.88).
      Similarly, oxidative metabolism in stunned regions was significantly decreased at
      4 h (84% +/- 2% of remote, P < 0.001) and at 24 h (90% +/- 2% of remote, P =
      0.005) and recovered to near-normal levels after 1 wk of reperfusion (97% +/- 1%
      of remote, P = 0.024). The time course of change in postischemic dysfunction
      correlated with the recovery of oxidative metabolism (r=0.57; P=0.009).
      CONCLUSION: Myocardium subjected to repetitive stunning showed a prolonged yet
      reversible reduction in systolic function that was associated with a significant
      downregulation of glucose and oxidative metabolism despite restoration of normal
      myocardial blood flow. These findings suggest a unique metabolic adaptation in
      repetitive stunning that is different from that typically seen in clinical and
      experimental models of hibernation.

PMID- 10914915
TI  - Myocardial hibernation and stunning: still much to learn.

PMID- 10914916
TI  - Myocardial uptake of a (99m)Tc-nitroheterocycle in a swine model of occlusion and
      reperfusion.
AB  - The purpose of this study was to evaluate the window for scan positivity of the
      radiolabeled nitroheterocycle (99m)Tc-BRU-59-21 in the peri-ischemic period using
      a swine model of occlusion and reperfusion. METHODS: A balloon catheter was
      placed in the left anterior descending coronary artery in each of 19 domestic
      swine. Blood flow and hemodynamic measurements were made at baseline, during
      occlusion, and at 15 and 180 min after reperfusion. A dose of approximately 925
      MBq (99m)Tc-BRU-59-21 was injected before a brief (6 min) period of coronary
      occlusion at the following times: 15 min (n = 2), 5 min (n = 2), and 2.2 min (n =
      5). In 5 experiments the dose was injected 15 min after reperfusion. Animals
      underwent SPECT imaging 3 h later. Animals were then killed, and hearts were
      removed, sliced, stained with triphenyl tetrazolium chloride, and imaged on the
      detector. RESULTS: The risk region became ischemic during occlusion on the basis
      of severe reduction in blood flow and lactate production, but necrosis occurred
      in only 3 experiments. Focal tracer uptake was seen in the risk region in animals
      injected 5 and 2.2 min before occlusion but not in animals injected 15 min before
      occlusion and 15 min after reperfusion. CONCLUSION: The window for scan
      positivity for (99m)Tc-BRU-59-21 injected in the peri-ischemic period is short
      using this model of balloon occlusion and reperfusion in swine.

PMID- 10914917
TI  - Pharmacologic intervention with angiotensin II and kininase inhibitor enhanced
      efficacy of radioimmunotherapy in human colon cancer xenografts.
AB  - Induced hypertension and kininase inhibition can enhance tumor targeting of
      radiolabeled monoclonal antibody (MAb) by altering tumor circulation. This study
      investigated the effect of this manipulation on the antitumor efficacy of
      radioimmunotherapy (RIT). METHODS: Mice bearing human colon cancer xenografts
      were administered 2.0 microg/kg/min of angiotensin II (AT-II) for 1 h and 30
      microg of a kininase inhibitor, enalapril maleate, before the administration of
      3.7 MBq (131)I-A7, an IgG1 against 45-kDa glycoprotein on colorectal cancer, and
      tumor growth was observed thereafter. The mechanism of the manipulation effect
      was investigated by estimation of the tissue absorbed dose and radioluminography
      of tumors. RESULTS: The pharmacologic manipulation with AT-II and enalapril
      improved the tumor quadrupling time (Tq) of 3.7 MBq RIT from 24.3 +/- 2.75 d to
      33.1 +/- 2.83 d (P < 0.05). Addition of this manipulation made 3.7 MBq RIT as
      effective as 9.25 MBq RIT alone (Tq, 37.2 +/- 2.97 d). Dose estimation showed
      that the manipulation increased the tumor absorbed dose 1.55-fold without
      affecting the doses to normal tissues. Uniform intratumoral distribution in the
      manipulated tumors was shown by radioluminography. CONCLUSION: Larger and more
      uniform tumor radiation produced by this pharmacologic manipulation can benefit
      RIT with (131)I-MAb.

PMID- 10914918
TI  - Transport mechanisms of 3-[123I]iodo-alpha-methyl-L-tyrosine in a human glioma
      cell line: comparison with [3H]methyl]-L-methionine.
AB  - The amino acid analog 3-[(123)I]iodo-alpha-methyl-L-tyrosine (IMT) is under
      clinical evaluation as a SPECT tracer of amino acid transport in brain tumors.
      This study investigated the carrier systems involved in IMT transport in human
      glioma cells in comparison with [3H-methyl]-L-methionine (3H-MET). METHODS: Human
      glioma cells, type 86HG-39, were cultured and incubated for 1 min at 37 degrees C
      with IMT and 3H-MET in the lag phase (1.2 d after seeding), exponential growth
      phase (3 d after seeding), and plateau phase (8 d after seeding). Experiments
      were performed in the presence and absence of Na+, during inhibition of system L
      amino acid transport by 2-aminobicyclo[2.2.1 ]heptane-2-carboxylic acid (BCH),
      and during inhibition of system A amino acid transport by 2-(methylamino)
      isobutyric acid (MeAIB). RESULTS: IMT and 3H-MET uptake decreased by 55%-73% when
      the cells entered from the exponential growth phase into the plateau phase (P<
      0.05; n = 3-11). Inhibition by BCH reduced uptake of IMT in the lag phase,
      exponential growth phase, and plateau phase by 90%-98% (P < 0.001; n = 3-6) and
      the uptake of 3H-MET by 73%-83% (P < 0.001; n = 3-11). In a Na+-free medium 3H
      MET uptake was reduced by 23%-33% (P < 0.05; n = 3-11), whereas IMT uptake was
      not significantly different. MeAIB showed no significant effect on IMT or 3H-MET
      uptake in either phase. CONCLUSION: Transport of both IMT and 3H-MET depends on
      the proliferation rate of human glioma cells in vitro and is dominated by BCH
      sensitive transport. These data indicate that system L is induced in rapidly
      proliferating glioma cells and is the main contributor to the uptake of both
      tracers. 3H-MET transport showed a minor Na+ dependency that was not attributable
      to system A. The similarity of transport mechanisms of both tracers emphasizes
      the clinical equivalence of IMT SPECT and (11)C-MET PET for the diagnostic
      evaluation of gliomas.

PMID- 10914919
TI  - Progressive nuclear translocation of somatostatin analogs.
AB  - Optimal cancer radiotherapy using Auger electron emitters requires selective
      localization of radionuclides in close proximity to tumor DNA. METHODS:
      Intracellular trafficking of (125)I-Tyr1-somatostatin-14 somatotropin-release
      inhibiting factor (SRIF) and 2 of its analogs, (125)I-WOC 4a and (111)In
      pentetreotide, was studied in human neuroblastoma cells. RESULTS: After 24-h
      incubation, SRIF was degraded or recycled, whereas its protease-resistant analogs
      progressively accumulated in nuclear fractions. (111)In-pentetreotide binding to
      DNA increased over time in somatostatin receptor-positive cells but not in
      somatostatin receptor-negative cells. CONCLUSION: These in vitro studies show
      that prolonged exposure to radiolabeled SRIF analogs significantly increases
      their cellular internalization, nuclear translocation, and DNA binding.
      Clinically, infusion of radiolabeled somatostatin analogs may enhance tumor
      uptake and retention and provide more effective in situ radiotherapy.

PMID- 10914920
TI  - Reduction of background activity through radiolabeling of antifibrin Fab' with
      99mTc-dextran.
AB  - Scintigraphic detection of occult disease is limited by background activity in
      the blood and in the extravascular space that reduces target-specific contrast.
      To lower nonspecific background activity, we have studied the in vivo
      biodistribution kinetics of a clot-targeting molecule (MH1 Fab') attached to
      (99m)Tc-dextran. We tested the hypothesis that the complex will have better
      background clearance than the directly radiolabeled clot-targeting molecule.
      METHODS: Fab' fragments of MH1 Fab' antifibrin antibody were coupled to (99m)Tc
      sulfhydryl dextran through disulfide exchange, and clot binding bioreactivity was
      tested in vitro and in vivo in a rabbit jugular vein thrombus model. To assess
      the background clearance kinetics and extravascular leakage, we studied (99m)Tc
      dextran, (99m)Tc-MH1 Fab', and the (99m)Tc-dextran-labeled MH1 Fab' complexes in
      rats. RESULTS: (99m)Tc-radiolabeled dextran derivatives were radiochemically
      stable and retained clot-binding bioreactivity in vivo. In the rat model, blood
      and tissue clearance of the (99m)Tc-dextran MH1 Fab' constructs was substantially
      improved relative to directly radiolabeled MH1 Fab'. At 1 h, total and
      extravascular tracer localizations in lung and muscle were significantly lower
      for 99mTc-dextranradiolabeled MH1 Fab' than for (99m)Tc-MH1 Fab' (P < 0.05).
      CONCLUSION: The study observations suggest that radiolabeling through a (99m)Tc
      dextran moiety may improve the detection of pulmonary emboli and other clinically
      important fixed intravascular targets by lowering nonspecific background
      activity.

PMID- 10914921
TI  - Simple new method for effective concentration of 188Re solutions from alumina
      based 188W-188Re generator.
AB  - (188)Re is a useful generator-produced radioisotope currently under evaluation
      for a variety of therapeutic applications, including bone pain palliation and
      intravascular radiation therapy. Because the (188)W parent is available only in a
      relatively low specific activity (<0.15-0.19 GBq/mg) from reactor irradiation of
      enriched (186)W, relatively large volumes of 0.9% saline (>15 mL) are required
      for elution of the (188)Re daughter from traditional alumina-based (188)W-(188)Re
      generators. Because these large bolus volumes result in solutions with a
      relatively low specific volume activity of (188)Re (<1 GBq/mL for the 18.5-GBq
      generator), the availability of effective methods for eluent concentration is
      important. Our new approach is based on the use of 0.3 mol/L ammonium acetate as
      a representative salt of a weak acid instead of saline for generator elution.
      METHODS: After generator elution, the ammonium acetate generator eluent (15-20
      mL) is passed through a tandem IC-H Plus cation (Dowex-H)-anion (QMA Light)
      column system. Exchange of ammonium cations with hydrogen ions on the cation
      column forms an acetic acid solution containing perrhenate anions from which the
      macroscopic levels of the acetate anion of the eluent have been effectively
      removed. Because perrhenic acid is fully dissociated at this pH, the QMA Light
      column specifically traps the (188)Re-perrhenate, which is subsequently eluted
      with a low volume (<1 mL) of saline. Concentration ratios greater than 20:1 are
      readily achieved with this method. RESULTS: A typical clinical-scale generator
      loaded with 19.2 GBq (188)W was used to validate the approach. Saline elution
      provided (188)Re in a 75%-80% yield. Although elution with 0.15 mol/L NH4OAc gave
      lower yields (55%-60%), use of 0.3 mol/L NH4OAc provided yields comparable with
      those of saline (70%-75%). (188)W parent breakthrough was not detected after
      passage of the bolus through the tandem concentration system. Bolus volumes of 15
      20 mL, which initially contained as much as 11.1-14.8 GBq (188)Re, were readily
      concentrated to less than 1 mL saline using QMA Light cartridges. The generator
      was evaluated for more than 3 mo with no decrease in performance. CONCLUSION:
      This approach represents a simple, rapid, and effective method using inexpensive
      disposable components of concentrating solutions of (188)Re for preparation of
      therapeutic agents.

PMID- 10914922
TI  - 6-O-(2-[18F]fluoroethyl)-6-O-desmethyldiprenorphine ([18F]DPN): synthesis,
      biologic evaluation, and comparison with [11C]DPN in humans.
AB  - 6-O(2-[18F]fluoroethyl)-6- -desmethyldiprenorphine ([18F]DPN) was developed and
      biologically evaluated. Results of animal experiments, binding studies in vivo,
      and a human PET study are reported and compared with those of [11C]DPN. METHODS:
      [18F]DPN was obtained by 18F-fluoroethylation of 3-O-trityl-6-O
      desmethyldiprenorphine and subsequent deprotection in good radiochemical yields
      (23% +/- 7%; 100 min; 37 TBq/mmol). Binding of [18F]DPN to mu, kappa, and delta
      opioid receptors was shown by autoradiography studies on rat brain slices.
      Quantification of cerebral opioid receptor binding in men was performed by
      spectral analysis of a dynamic PET scan (25 frames, 90 min) after intravenous
      application of 63 MBq [18F]DPN (36 GBq/micromol) and correction for metabolites.
      RESULTS: [18F]DPN shows high affinity to opioid receptors. Parametric images
      (impulse response function at 60 min) of this human study showed a binding
      pattern of [18F]DPN equal to that of a control group (n = 9 healthy volunteers)
      after administration of [11C]DPN. CONCLUSION: The advantage of the longer half
      life of 18F will allow extended scanning periods, more flexible interventions
      (e.g., displacement studies), and DPN to be available to PET centers without an
      on-site cyclotron.

PMID- 10914923
TI  - Intrinsic dual-energy processing of myocardial perfusion images.
AB  - We have developed a software-based method for processing dual-energy 201TI SPECT
      emission projection data with the goal of calculating a spatially dependent index
      of the local impact of gamma-ray attenuation. We refer to this method as
      intrinsic dual-energy processing (IDEP). METHODS: IDEP exploits the differential
      attenuation of lower energy emissions (69-83 keV) and higher energy emissions
      (167 keV) resulting from the decay of 201TI to characterize the relative degree
      of low-energy gamma-ray attenuation throughout the myocardium. In particular,
      IDEP can be used to estimate the relative probability that a low-energy gamma-ray
      emitted from a particular region of the myocardium is detected during the
      acquisition of SPECT projection data. Studies on phantoms and healthy human
      volunteers were performed to determine whether the IDEP method yielded detection
      probability images with systematic structure visible above the noise of these
      images and whether the systematic structure in the detection probability images
      could be rationalized physically. In patient studies, the relative regional
      detection probabilities were applied qualitatively to determine the likely
      effects of attenuation on the distribution of mapped photon emissions. RESULTS:
      Measurements of the detection probability in uniform phantoms showed excellent
      agreement with those obtained from computer simulations for both 180 degrees and
      360 degrees acquisitions. Additional simulations with digital phantoms showed
      good correlation between IDEP-estimated detection probabilities and calculated
      detection probabilities. In patient studies, the IDEP-derived detection
      probability maps showed qualitative agreement with known nonuniform attenuation
      characteristics of the human thorax. When IDEP data were integrated with the
      findings on the emission scan, the correlation with coronary anatomy (known in 6
      patients and hypothesized on the basis of clinical and electrocardiographic
      parameters in 5 patients) was improved compared with evaluating the mapped
      emission image alone. CONCLUSION: The IDEP method has the potential to
      characterize the attenuation properties of an object without use of a separate
      transmission scan. Coupled with the emission data, it may aid coronary diagnosis.

PMID- 10914924
TI  - When the lights go on again: an unusual problem with a gamma camera.

PMID- 10914925
TI  - Evaluation of motion-correction techniques in cardiac SPECT.

PMID- 10914926
TI  - National and state-specific pregnancy rates among adolescents--United States,
      1995-1997.
AB  - Each year in the United States, 800,000-900,000 adolescents aged < or = 19 years
      become pregnant. Adolescent pregnancy and childbearing have been associated with
      adverse health and social consequences for young women and their children. This
      report presents estimated national numbers of pregnancies and national and state
      specific pregnancy rates for adolescents aged < or = 19 years from 1995 to 1997.
      The findings indicate a decline in national and state-specific adolescent
      pregnancy rates during 1995-1997, and a continuing downward trend beginning in
      the early 1990s (1,2,4).

PMID- 10914927
TI  - Silicosis screening in surface coal miners--Pennsylvania, 1996-1997.
AB  - Silicosis is an occupational respiratory disease caused by inhaling respirable
      crystalline silica dust. Silicosis is irreversible, often progressive (even after
      exposure has ceased), and potentially fatal. Exposure to silica dust occurs in
      many occupations, including mining (1). During 1996-1997, surface coal miners at
      eight sites in Pennsylvania were screened to estimate the prevalence of
      silicosis, to identify risk factors for silicosis, and to refer miners with a
      possible diagnosis of silicosis or other conditions for medical evaluation and
      treatment. This report summarizes the results of the screening, which indicated
      that an increased prevalence of and risk for silicosis is associated with miners'
      age and years of drilling experience, and provides recommendations for preventing
      silicosis among miners.

PMID- 10914928
TI  - Hepatitis B vaccination coverage among Asian and Pacific Islander children-
      United States, 1998.
AB  - Asian and Pacific Islander (API) children in the United States have high rates of
      hepatitis B virus (HBV) infection (1-3). To prevent these infections, hepatitis B
      vaccination has been recommended for these children since the vaccine was first
      licensed by the Food and Drug Administration in 1981 (4). Recommendations have
      included universal hepatitis B vaccination of API infants beginning in 1990 and
      catch-up vaccination for API children aged <7 years (5). These recommendations
      were reinforced in 1991 when hepatitis B vaccination was recommended for all
      infants, particularly in populations such as API children with high rates of
      early childhood HBV infection (6). In 1995, vaccination was recommended for
      unvaccinated API children aged <11 years and catch-up vaccination for children
      aged 11-12 years who had not received hepatitis B vaccine (HepB) (7). Series
      completion among API children aged 19-35 months increased from 39% in 1994 to 88%
      in 1997 (8). However, among older API children, hepatitis B vaccination coverage
      was 10% in 1995 (7). In 1998, to examine trends in hepatitis B vaccination catch
      up coverage among API children born before 1994, surveys were conducted in six
      U.S. cities. This report summarizes the results of the surveys, which indicate
      varying coverage among API children and suggest a need for continued focused
      vaccination programs for this population.

PMID- 10914929
TI  - Delayed supply of influenza vaccine and adjunct ACIP influenza vaccine
      recommendations for the 2000-01 influenza season. Advisory Committee on
      Immunization Practices.
AB  - Annual vaccination against influenza is the primary means for minimizing serious
      adverse outcomes from influenza virus infections. These infections result in
      approximately 20,000 deaths and 110,000 hospitalizations per year in the United
      States (1). The amount of trivalent inactivated influenza vaccine produced for
      distribution in the United States has increased substantially; in 1999, four
      manufacturers produced a combined total of 80 to 85 million doses.

PMID- 10914930
TI  - Summary of the joint statement on thimerosal in vaccines. American Academy of
      Family Physicians, American Academy of Pediatrics, Advisory Committee on
      Immunization Practices, Public Health Service.
AB  - In June 2000, a joint statement on thimerosal in vaccines was prepared by the
      American Academy of Family Physicians (AAFP), the American Academy of Pediatrics
      (AAP), the Advisory Committee on Immunization Practices (ACIP), and the Public
      Health Service (PHS) in response to 1) the progress in achieving the national
      goal declared in July 1999 to remove thimerosal from vaccines in the recommended
      childhood vaccination schedule, and 2) results of recent studies that examined
      potential associations between exposure to mercury in thimerosal-containing
      vaccines and health effects. In this statement, AAFP, AAP, ACIP, and PHS
      recommend continuation of the current policy of moving rapidly to vaccines that
      are free of thimerosal as a preservative. Until adequate supplies are available,
      use of vaccines that contain thimerosal as a preservative is acceptable.

PMID- 10914931
TI  - Compendium of measures to control Chlamydia psittaci infection among humans
      (psittacosis) and pet birds (avian chlamydiosis), 2000. Centers for Disease
      Control and Prevention.
AB  - Psittacosis--also known as parrot fever and ornithosis--is spread by a bacterial
      infection of birds that can cause severe pneumonia and other serious health
      problems among humans. From 1988 through 1998, 813 cases of psittacosis
      (infection with Chlamydia psittaci) were reported to CDC, and most resulted from
      exposure to infected pet birds, usually cockatiels, parakeets, parrots, and
      macaws. In birds, C. psittaci infection is referred to as avian chlamydiosis
      (AC). Infected birds shed the bacteria through feces and nasal discharges, and
      humans become infected from exposure to these materials. This compendium provides
      information about psittacosis and AC to public health officials, physicians,
      veterinarians, the pet bird industry, and others concerned about controlling
      these diseases and protecting public health. The recommendations in this
      compendium provide standardized procedures for controlling AC in birds, a vital
      step to protecting human health.

PMID- 10914932
TI  - Compendium of animal rabies prevention and control, 2000. National Association of
      State Public Health Veterinarians, Inc.
AB  - The purpose of this Compendium is to provide rabies information to veterinarians,
      public health officials, and others concerned with rabies prevention and control.
      These recommendations serve as the basis for animal rabies-control programs
      throughout the United States and facilitate standardization of procedures among
      jurisdictions, thereby contributing to an effective national rabies-control
      program. This document is reviewed annually and revised as necessary.
      Immunization procedure recommendations are contained in Part I; all animal rabies
      vaccines licensed by the United States Department of Agriculture (USDA) and
      marketed in the United States are listed in Part II; Part III details the
      principles of rabies control.

PMID- 10914933
TI  - Treatment of the myeloproliferative disorders with 32P.
AB  - The use of radioactive phosphorus (32P) to treat the myeloproliferative disorders
      (chronic leukemia, polycythemia vera and essential thrombocythemia) began in 1939
      when John H. Lawrence treated the first patient on the basis of work done in the
      laboratory animals that found localization of the radioisotope in the spleen,
      liver, bone and in leukemic cells sufficient to indicate a therapeutic potential.
      After World War II when 32P became widely available, it was used extensively to
      treat the chronic leukemias and polycythemia vera. Its use in the treatment of
      essential thrombocythemia began later in 1950. Today it is not widely used in the
      treatment of the chronic leukemia, if at all, its use in polycythemia vera
      appears to have decreased substantially and replaced by hydroxyurea, and its use
      in the management of essential thrombocythemia is not widespread. In each
      instance it has been replaced by a drug developed for use in cancer chemotherapy,
      and in some instances by interferon. It probably has wider use in polycythemia
      vera in the rest of Western Europe than in the UK, and there are cogent reasons
      to suggest that it may be the best tool for the treatment of polycythemia vera.
      Thus have we discarded a treatment modality that in polycythemia vera may be the
      best?

PMID- 10914934
TI  - Immunophenotypic discrepancies between granulocytic and erythroid lineages in
      peripheral blood of patients with paroxysmal nocturnal haemoglobinuria.
AB  - In paroxysmal nocturnal haemoglobinuria (PNH), somatic mutation of the PIG-A gene
      is thought to result in altered expression of glycosylphosphatidylinositol (GPI)
      anchored proteins. This study was performed to determine if there were any
      heterogeneities of cellular phenotypes between two major peripheral blood cells,
      erythrocytes and granulocytes. Using CD59-based immunocytometry, the patterns of
      CD59 expression were shown to be conserved in the circulating erythroid cells
      (reticulocytes and mature erythrocytes) in all 29 patients with PNH. Twenty-one
      patients had distinct combinations of PNH type I, II, and III cells in different
      lineages. Only eight patients exhibited similar patterns of CD59 expression
      between the two lineages. Approximately one third of the patients had PNH type II
      cells in either or both of the two lineages indicating variable lineage
      involvement. The proportion of abnormal granulocytes was higher than those of
      abnormal reticulocytes and erythrocytes. In patients with appropriate
      erythropoietic responses to haemolysis (RPI > 2.0), shift reticulocytes display
      predominantly PNH phenotypes. These immature erythroid cells with altered
      expression of GPI-anchored proteins may dominate the peripheral blood during
      periods of increased marrow activity resulting in greater phenotypic mosaicism in
      such patients. Discrepancies in expression of GPI-anchored proteins in PNH which
      are highly variable between the two lineages may be the result of their different
      life spans and the influence of complement-mediated cytolysis. The phenomena also
      indicated the possible occurrence of more than one PNH clones with variable
      clonal dominance.

PMID- 10914935
TI  - Long-term follow-up of autologous stem-cell transplantation for follicular and
      transformed follicular lymphoma.
AB  - Despite the fact that follicular lymphomas are both chemo- and radiosensitive,
      the disease is generally non-curable. These lymphomas often undergo
      transformation to a more malignant state. In order to improve the prognosis, high
      dose treatment with stem cell support has been tested, but its role in the
      treatment of this disease is still unclear. Fourteen men and eight women with a
      median age of 45 yr (34-59) were treated with high-dose therapy with autologous
      stem cell transplantation between 1987 and 1996. The patients were selected to
      undergo intensive therapy because of an estimated short survival (median < 3 yr),
      even though they had chemosensitive disease and adequate performance status.
      Eleven patients' lymphomas had transformed, and the other eleven patients had one
      or more unfavourable prognostic signs such as advanced stage, bulky disease,
      multiple relapses, or short remission duration. The conditioning regimen has
      varied over the period, but BEAC (Becenum, etoposide, cytarabine,
      cyclophosphamide) or etoposide/cyclophosphamide with or without total body
      irradiation (TBI) was used in most patients. Nine patients had their stem cells
      purged. After a median follow-up time of 74 months overall survival was 81% and
      disease-free survival 72%. One toxic procedure-related death occured. There was
      no difference in outcome between patients with a transformed lymphoma compared to
      those without transformation. The patients treated with TBI had a significantly
      worse outcome. Toxicity was also much higher in TBI-treated patients, including
      four cases of secondary malignancy (three myelodysplastic syndrome (MDS) cases
      and one patient with breast carcinoma). This retrospective study, with the
      longest follow-up time so far reported, shows a promising 6-yr DFS of 72% in a
      group of follicular lymphoma patients with a bad prognosis. The outcome of
      patients with transformed lymphoma compared to historical controls is especially
      encouraging. The high incidence of MDS is worrying. The role of TBI should be
      questioned because this and other studies have not shown any advantage of using
      TBI. In the absence of randomised trials the role of high-dose treatment for
      patients with follicular lymphoma is still not defined.

PMID- 10914936
TI  - Prognostic value of p53 gene mutations and the product expression in de novo
      acute myeloid leukemia.
AB  - In acute myeloid leukemia (AML), p53 mutations are reportedly infrequent but
      associated with a poor prognosis. The majority of mutations are missense
      mutations, which generally lead to accumulation of nuclear p53 protein. However,
      the prognostic significance of the accumulation remains unknown in AML. In this
      study, we compared the prognostic value of p53 mutations versus accumulation of
      the product. p53 mutations were found in 9 (4.5%) of 200 patients with de novo
      AML. The p53 mutation detectable (mutation+) group had a worse prognosis (p =
      0.0009) than the mutation not detectable (mutation-) group. Multivariate analysis
      showed that the p53 mutation was an independent factor (p = 0.005) for short
      overall survival as well as 60 yr or older (p = 0.001) and unfavorable karyotypes
      (p = 0.001). In 79 of the 200 patients, the expression of p53 was studied by
      immunocytochemistry (ICC) using anti-p53 monoclonal antibody (DO-7). All samples
      carrying missense mutations (N = 6) were positive for ICC in over 15% of nuclei
      of each sample, chosen as the optimized cutoff value of p53 accumulation.
      Accumulation was thus found in 14 of the 79 patients. However, there was no
      prognostic difference according to the accumulation, because the mutation
      /accumulation+ group (N = 8) tended to have a good prognosis. These findings
      indicate that molecular detection of p53 mutations yields better prognostic
      information than ICC. In a subset of AML, p53 protein might be accumulated
      without mutation presumably due to upstream signals of p53.

PMID- 10914937
TI  - Complex chromosomal aberrations in chronic lymphocytic leukemia are associated
      with cellular drug and irradiation resistance.
AB  - Drug resistance is a major problem in chemotherapy of chronic lymphocytic
      leukemia (CLL). The genetic basis and molecular pathogenesis of drug resistance
      in CLL remain poorly understood. Here, we have investigated the association
      between chromosomal aberrations and cellular resistance of CLL cells against
      seven drugs, gamma and ultraviolet irradiation. Samples were obtained from 35
      patients having a classical form of B-CLL. Chromosomal aberrations were first
      analyzed by traditional karyotyping improved by using optimized mitogen
      combinations. DNA sequence copy number changes throughout the genome were next
      screened by comparative genomic hybridization. Finally, fluorescence in situ
      hybridization was used to detect trisomy 12 and loss of Rb and deletions at
      chromosome 11. The cellular sensitivity in vitro was assessed by the reduction of
      macromolecular protein synthesis measured as incorporation of radioactive L
      leucine as an endpoint. The overall analysis disclosed a statistically highly
      significant difference in cellular drug resistance between patients having at
      least three aberrations compared with patients with fewer or no aberrations. This
      strongly indicates that complex rather than simple molecular mechanisms are
      responsible for the drug and irradiation resistance in CLL. According to
      published results, complex aberrations are constantly associated with poor
      prognosis in CLL. We demonstrated here that complex chromosomal aberrations were
      associated with cellular irradiation and drug resistance, which, on the other
      hand, may be responsible for the poor clinical outcome in CLL.

PMID- 10914938
TI  - Cytogenetic and FISH studies of a single center consecutive series of 152
      childhood acute lymphoblastic leukemias.
AB  - Between 1977 and 1996, cytogenetic investigations were performed on 182 childhood
      (< or = 16 yr) acute lymphoblastic leukemias (ALL), constituting 94% (182 of 194)
      of all ALL patients diagnosed and treated at the Departments of Pediatrics, Lund
      and Malmo University Hospitals, Sweden, during these two decades. The cytogenetic
      analyses were successful in 152 cases (84%). The failure rate was higher for the
      ALL investigated before 1987 (30% vs. 4%, p < 0.0001), and also the incidence of
      cytogenetically normal cases was higher during 1977-86 (43% vs. 25%, p < 0.05).
      Clonal chromosomal abnormalities were found in 103 (68%) ALL. Structural
      rearrangements were detected, by chromosome banding alone, in 76 cases (50%).
      Fluorescence in situ hybridization (FISH) was used to identify cases with
      t(12;21), 11q23 rearrangements, and 9p deletions, using probes for ETV6/CBFA2,
      MLL, and CDKN2A/B, in 72 cases from which cells in fixative and/or unstained
      metaphase preparations were available. In total, the most common structural
      rearrangements were del(9p) (17%), t(12;21) (15%), del(6q) (8%), and MLL
      rearrangements (4%). Six (32%) of nineteen cytogenetically normal ALL analyzed by
      FISH harbored cryptic abnormalities; three displayed t(12;21) and four had
      del(9p), one of which also carried a t(12;21). Five (45%) of the t(12;21)
      positive ALL showed +der(21)t(12;21) or ider(21)(q10)t(12;21), resulting in the
      formation of double fusion genes. Among the more rare aberrations, eight
      structural rearrangements were identified as novel recurrent ALL-associated
      abnormalities, and nine cases harbored rearrangements previously not reported.
      Sixteen cases displayed karyotypically unrelated clones at different
      investigations. Seven ALL (5%) showed simple chromosomal changes, unrelated to
      the aberrations detected at diagnosis, during morphologic and clinical remission,
      and in all but one instance the patients remained in remission, with the abnormal
      clone disappearing in subsequent investigations. This indicates that the
      emergence of novel clonal chromosomal aberrations during remission in childhood
      ALL is rather common and does not by necessity predict a forthcoming relapse.

PMID- 10914939
TI  - Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis.
AB  - Since high levels of serum IL-6 predict a poor prognosis of patients with
      multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM),
      correlates with clinical or biochemical findings or has prognostic significance
      in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in
      the sera in 45 (55%). Serum OSM had a borderline statistical correlation with
      serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074)
      concentrations. However, OSM did not have prognostic significance alone or in
      combination with other factors. The median survival of patients with detectable
      serum OSM concentration was 41 months (range 2-124 months) and of OSM negative
      patients 35 months (1-75 months). Serum OSM concentration was not associated with
      clinical factors or severity of bone disease at diagnosis. We conclude that serum
      OSM concentration is not a prognostic factor in MM patients.

PMID- 10914940
TI  - A whole-blood flow cytometric assay for leukocyte CD11b expression using
      fluorescence signal triggering.
AB  - A flow cytometric assay for measurements of leukocyte CD11b expression in whole
      blood has been developed and evaluated. The method is based on triggering of the
      flow cytometer by a fluorescent pan leukocyte marker, RPE-CD45. This enabled flow
      cytometric analysis in whole blood, and avoidance of in vitro artefacts related
      to cell purification and hemolysis. Our methodological evaluation suggested the
      following routine procedure: sampling with sodium citrate as the anticoagulant,
      sample incubation at 22 degrees C, and mild sample fixation with 0.5%
      formaldehyde saline. The latter provided good sample stability during 24 h.
      Moreover, the assay provided good assay reproducibility, low labelling antibody
      consumption, and minimal sample manipulation (< 30 min) and acquisition time
      demands. The assay seems to reflect the CD11b expression of circulating
      leukocytes, and is also suitable for studies of agonist stimulated CD11b
      expression in leukocyte subpopulations in vitro. When full CD11b responsiveness
      to agonist stimulation is desired, samples should be incubated at 37 degrees C,
      but this also elevated CD11b expression in unstimulated samples. The present
      whole-blood technique is thus suitable for analyses of CD11b expression for both
      research and clinical routine laboratory use. The assay can easily be modified
      for measurements of other leukocyte antigens by use of other specific fluorescent
      antibodies.

PMID- 10914941
TI  - Detection of reticulated platelets: estimating the degree of fluorescence of
      platelets stained with thiazole orange.
AB  - The primary problem in the measurement of reticulated platelets (RP) stained with
      thiazole orange (TO) by flow cytometry is the definition of a threshold limit for
      fluorescence positivity. We evaluated settings for the threshold gate for TO
      positivity based on two principles: a fluorescence histogram (median FL1,
      Relative FL1) or a plot of forward light scatter (FSC; reflecting the
      distribution of the platelet size) versus fluorescence intensity (% RP). These
      methods were applied prospectively in examination of 54 healthy blood donors (16
      females) and a total of 50 blinded patient samples: pregnant women with
      thrombocytopenia (Group 1A, n = 11), thrombocytopenic women after delivery (Group
      1B, n = 9) and healthy women with a thrombocytopenic newborn (Group 2, n = 30).
      Group 1A displayed higher median FL1 (mean 306, CI 279-332) as compared to that
      of Group 2 (mean 266, CI 255-277; p = 0.0038) or to that of the female controls
      (mean 249, CI 231-268; p < 0.001). Relative FL1 was also higher in the patients
      of Group 1A than those of Group 2 (p = 0.037). When analysing the % RP, the
      difference between these groups was not significant. In the patients (n = 50),
      the median FSC (mean 407, SD 40, CI 395-418) was also higher than that of the
      controls (n = 54; mean 383, SD 25, CI 376-390; Mann-Whitney U-test, p = 0.0015).
      In Group 1A, a significant correlation was observed between the Patient median
      FL1 and Patient median FSC (r = 0.62, p = 0.043). When developing methods for the
      measurement of RP, it seems to be useful to analyse the data with more than one
      principle to define the threshold limit for TO positivity.

PMID- 10914942
TI  - Sweet's syndrome and Pneumocystis carinii pneumonia: two sequelae of low-dose
      cytosine arabinoside therapy in a patient with acute myeloid leukemia.
AB  - Cytosine arabinoside in low dose is sometimes employed for treating acute myeloid
      leukaemia. We report here a case of acute myeloid leukemia, treated with low-dose
      cytosine arabinoside, who developed acute febrile neutrophilic dermatosis and
      Pneumocystis carinii pneumonia after attainment of remission. A direct effect of
      cytosine arabinoside on neutrophil function and an immunosuppressive potential in
      lower doses could be speculated.

PMID- 10914943
TI  - Successful treatment of thymoma-associated pure red cell aplasia with intravenous
      immunoglobulins.
AB  - Repeated cycles of intravenous immunoglobulins (IVIG) have been reported to be
      successful in a few patients with idiopathic pure red cell aplasia (PRCA) or
      associated with another pathology. The efficacy of this treatment for PRCA with
      thymoma has not been reported previously. We describe here the case of a 75-yr
      old man who presented with PRCA associated with a benign thymoma. After failure
      of thymectomy, corticosteroids and octreotide, a complete durable remission was
      obtained after a single 5-d cycle of IVIG.

PMID- 10914944
TI  - Cryoglobulin detection from a blood smear leading to the diagnosis of multiple
      myeloma.

PMID- 10914945
TI  - Prevalence of Factor V Leiden in three ethnic groups of patients with deep vein
      thrombosis in the Western Cape province of South Africa.

PMID- 10914946
TI  - A homozygosity state for 20210A prothrombin variant in a young woman as cause of
      a deep venous thrombosis during pregnancy.

PMID- 10914947
TI  - More on the relationship between cystic fibrosis and venous thrombosis.

PMID- 10914948
TI  - Acute lymphoblastic leukaemia presenting as an enlarged goitre in a pregnant
      woman with Graves' disease.

PMID- 10914949
TI  - Reactivation of hepatitis B virus infection in an anti-HBc and anti-HBs positive
      patient after allogeneic bone marrow transplantation.

PMID- 10914950
TI  - No response to cladribine in five patients with chronic cold agglutinin disease.

PMID- 10914951
TI  - Iron balance between mother and infant during pregnancy and breastfeeding.

PMID- 10914953
TI  - Foetal size to final height.
AB  - It is well known that some adult diseases, such as cardiovascular diseases, may
      be programmed during foetal life. It is not clear, however, whether final height
      may be predicted from foetal growth. A longitudinal cohort of full-term healthy
      Swedish babies (n = 3,650) was followed up from birth to maturity in a population
      based growth study. Length or height and its changes were analysed from birth to
      18 y of age; 2,807 children, with data available on birth length, final height
      and parental height, were included in this analysis. The result clearly shows
      that length at birth relates to final height. In terms of standard deviation
      scores (SDS), the mean difference in length at birth from the mean was greatly
      decreased in final height, but retained the same order as was seen at birth. In
      terms of centimeter difference from the reference mean values, the difference in
      length at birth remained roughly stable into final height. For instance, babies 5
      cm above or below the mean birth length will end up approximately 5 cm above or
      below the mean in final height. Parental height-a surrogate value of the genetic
      final height potential of an individual-is shown to influence postnatal growth in
      height strongly. However, the difference from the mean in length at birth
      remained into adulthood within the same midparental height group. CONCLUSION:
      This study reveals that trends in foetal linear growth continue into maturity.
      Foetal growth is a significant predictor of postnatal growth. Final height is
      dependent on both the magnitude of foetal growth and the genetic potential in
      stature, and appears to some extent to be programmed from foetal growth.

PMID- 10914952
TI  - A future for neonatal alpha1-antitrypsin screening?
AB  - A WHO expert group recommends neonatal screening for alpha1-antitrypsin
      deficiency (alpha1ATD). Homozygous alpha1ATD PiZZ occurs in 1 in 5,000 of the
      U.S. Caucasian population and up to 1 in 500 individuals of the European
      population, with a large regional variation. It is a risk factor that predisposes
      mainly to liver disease in early infancy and emphysema in early adulthood. Most
      importantly, smoking decreases the duration of the asymptomatic phase and life
      expectancy by 10-20 y. The Swedish alpha1AT screening programme and subsequent
      information and advice prevented the majority of adolescents from starting to
      smoke. The involved parents and alpha1ATD adolescents retrospectively recommended
      neonatal screening. Potential advantages of neonatal alpha1AT screening are:
      early diagnosis and treatment of neonatal liver disease, optimal treatment of
      fever and bacterial infections theoretically preventing liver cell damage,
      genetic advice and information about the consequences of passive and active
      smoking. Potential advantages of postponing screening until age 11-12 y are:
      identification of alpha1ATD close to the age when smoking may start, and
      possibility for the child to take part in the screening decision. Disadvantages
      of alpha1AT screening are: psychosocial reactions-the mother probably being most
      vulnerable in the neonatal period-and discrimination by insurance companies and
      employers. Important uncertainties are: lack of knowledge concerning
      participation in a voluntary alpha1AT screening, psychosocial reactions and the
      efficacy of anti-smoking advice if the information is given to school-age
      children and families. Thus the question whether and when to screen for alpha1ATD
      is still the topic of lively debate.

PMID- 10914954
TI  - New reference for the age at childhood onset of growth and secular trend in the
      timing of puberty in Swedish.
AB  - The objectives of the present work were to present a new reference for the age at
      childhood onset of growth and to investigate the secular trend in the timing of
      puberty in a community-based normal population in Sweden. A total of 2,432
      children with longitudinal length/height data from birth to adulthood were used
      to determine the two measures by visual inspection of the measured attained
      length/height and the change in growth velocity displayed on a computer-generated
      infancy-childhood-puberty (ICP) based growth chart. The series represents a
      sample of normal full-term children born around 1974 in Goteborg, Sweden. We
      found about 10% of children were delayed (>12 mo of age) in the childhood onset
      of growth based on the previous reported normal range, i.e. 14% in boys and 8% in
      girls. Distribution of the age at childhood onset of growth was skewed. The
      medians were 10 and 9 mo for boys and girls, respectively. After natural
      logarithmic transformation, the mean and standard deviation (SD) were 2.29 (anti
      log 9.9 mo) and 0.226 for boys, 2.23 (anti-log 9.3 mo) and 0.220 for girls,
      respectively. The 95% normal ranges were 6.3-15.4 and 6.0-14.3 for boys and
      girls, respectively. The distribution of the timing of PHV was close to the
      normal distribution. The mean values were 13.5 y for boys and 11.6 y for girls
      with 1 y SD for both sexes. CONCLUSION: A downward secular trend in the onset of
      puberty was clearly shown in the population. The age at childhood onset of growth
      did not correlate with the timing of puberty (r = -0.01 and 0.05, p > 0.7 and 0.1
      in boys and girls, respectively). Normal ranges of the age at childhood onset of
      growth are in need of revise, as this study indicates. The new reference
      presented here could be a reliable indicator in further studies.

PMID- 10914955
TI  - Effect of growth hormone therapy on feeding problems and food intake in children
      with growth disorders.
AB  - To assess the effect of therapeutic doses of growth hormone (GH) on the feeding
      problems, food intake, body fat and mealtime interactions of children with growth
      disorders, an age-matched group of 46 children with Turner syndrome (TS) or
      Silver Russell syndrome (SRS) was examined using questionnaire measures and
      direct observation. The children's body fat was measured using bio-electrical
      impedance analysis and skinfold thickness measurements. Children receiving GH
      consumed significantly more energy, protein, fat and carbohydrate than did the
      children who were not receiving GH, independent of the extent of the child's
      feeding problems. Children receiving GH had less body fat than did children who
      were not receiving GH. Children who were not receiving GH distracted their
      parents from the mealtime significantly more often and received more negative
      prompting and coaxing from their parents to eat than did children who were
      receiving GH. This study provides evidence to support the theory that appetite
      and intake is determined in part by growth and growth potential. Feeding problems
      seen in children with growth disorders are partly due to parental attempts to
      impose control over their child's intake, when their child consumes less than the
      parent believes to be adequate. CONCLUSION: GH has a significant impact on both
      the food intake and parent-child interaction at mealtimes of children with SRS
      and TS.

PMID- 10914956
TI  - Diagnosis of Chlamydia pneumoniae in community-acquired pneumonia in children in
      Chile.
AB  - The incidence of Chlamydia pneumoniae in community-acquired pneumonia in children
      was studied prospectively in 112 children aged 1 mo to 14 y. Diagnosis of C.
      pneumoniae was performed by polymerase chain reaction (PCR) on nasopharyngeal
      aspirates and serology by the microimmunofluorescence test on a single serum
      specimen. Three (2.7%) cases of pneumonia due to this agent were diagnosed by
      both PCR and serology. C. pneumoniae was not found in any of 62 children below 5
      y of age. In the age group 5-8 y, only 1/30 (3%) was found positive, and in the
      age group 9-14 y, C. pneumoniae was diagnosed in 2/20 (10%) children. CONCLUSION:
      Although the number of enrolled patients is small, and the diagnostic techniques
      used may have some limitations, the results of this study suggest that C.
      pneumoniae.plays a minor role in the aetiology of pneumonia in children less than
      9 y of age in our country. However, it should be considered as a potential agent
      in pneumonia in older children.

PMID- 10914957
TI  - Long-term effects of respiratory syncytial virus (RSV) bronchiolitis in infants
      and young children: a quantitative review.
AB  - One of the major questions regarding long-term side effects of bronchiolitis by
      respiratory syncytial virus (RSV) is whether or not it induces asthma in later
      life. In this quantitative review, the data of 10 controlled studies are
      analysed. METHODS: Follow-up studies of RSV bronchiolitis published between
      January 1978 and December 1998 were identified through a MEDLINE search. Studies
      were selected if (i) postnatal age at the time of the initial illness was below
      12 mo, (ii) all children were hospitalized for RSV bronchiolitis, (iii) the
      diagnosis RSV was virologically confirmed in all cases, and (iv) a control group
      was used. RESULTS: Six studies met all selection criteria. Up to 5 y of follow-up
      after RSV bronchiolitis in infancy, 40% of children reported wheezing as compared
      to only 11% in the control group (p <0.001). Between 5 and 10 y of follow-up 22%
      of the bronchiolitis group reported wheezing against 10% of the control group (p
      = 0.19). The incidence of recurrent wheezing as defined by three or more wheezing
      episodes also decreased with increasing years of follow-up: at 5 or more years of
      follow-up the difference between the RSV group and the control group was no
      longer significant. Furthermore, the presence of either a personal and/or a
      family history of either atopy and/or asthma did not differ between the two
      groups. CONCLUSIONS: Wheezing is common after RSV bronchiolitis in infancy. It
      may persist for > or = 5 y of follow-up. However, no significant difference
      between the RSV bronchiolitis and the control group was observed regarding
      recurrent wheezing by 5 y of follow-up. No significant difference between the RSV
      bronchiolitis and the control group were found regarding a personal history of
      atopy, a family history of atopy and/or asthma. Therefore it seems unlikely that
      RSV bronchiolitis is a cause of atopic asthma in later life.

PMID- 10914958
TI  - Neisseria meningitidis: evolution of penicillin resistance and phenotype in a
      children's hospital in Barcelona, Spain.
AB  - Neisseria meningitidis is the most prevalent micro-organism involved in
      paediatric bacterial meningitis in the Barcelona area in children over 3 mo of
      age and it is an important cause of morbidity and mortality in Spain. A total of
      498 strains of N. meningitidis, obtained between the years 1986 and 1997 from
      children with sepsis and/or meningitis, were characterized according to their
      serogroup and penicillin resistance; their distribution in serotypes and subtypes
      was studied from 1990. A decreasing tendency in the number of annual isolates was
      observed in this period. Most isolates belonged to serogroups B (403 strains) and
      C (77 strains). Serogroup C accounted for 1.8% of the strains in 1986 and 57.1%
      in 1997. The most prevalent phenotype between 1990 and 1996 was B:4:P1.15. but
      C:2b:P1.2,5 was the most prevalent in 1997. Overall penicillin-resistance rates
      ranged from 9.1% in 1986 (when a non-susceptible strain was isolated for the
      first time in the Hospital Sant Joan de Deu, Barcelona, Spain) to 71.4% in 1997,
      and it was more common among strains belonging to serogroup C (52% of resistant
      strains) than to serogroup B (22.1 % of resistant strains). The penicillin
      resistance level was low, MIC always < or = 0.5 microg/ml. The present increase
      in N. meningitidis group C isolates, mainly C:2b:P1.2,5, and the availability of
      preventive measures for this highly pathological and resistant phenotype, argues
      strongly for the establishment of an epidemiological monitoring system. Detection
      of penicillin resistance should be standardized worldwide in order to unify data
      from all laboratories. CONCLUSION: A shift between serogroups B and C is observed
      in Barcelona from 1986 to 1997, as well as a rapid distribution of decreased
      penicillin susceptibility.

PMID- 10914959
TI  - Bone biopsy results and serum bone turnover parameters in uremic children.
AB  - The aim of the study was to evaluate the prevalence of renal osteodystrophy types
      in children undergoing haemodialysis and continuous ambulatory peritoneal
      dialysis and to assess the usefulness of biochemical parameters in diagnosis of
      renal osteodystrophy. Bone biopsy and measurements of serum parathormone (iPTH)
      level, alkaline phosphatase (AP), osteocalcin (OC), procollagen 1C, calcium and
      phosphorus levels were performed in 51 children aged 11.5 +/- 2.9 y with end
      stage renal failure. Renal osteodystrophy (ROD) was diagnosed as follows:
      adynamic bone disease (ABD) in 14 (27%); normal bone histology (NB) in 19 (37%),
      osteomalacia (OM) in 1 (2%), mixed lesion (Mix) in 5 (10%) and
      hyperparathyroidism (HP) in 12 (24%) children. There was no difference in
      prevalence of ROD types between children on CAPD and HD. We found significant
      differences in the mean value of iPTH, OC levels and AP activity in HP vs NB and
      HP vs ABD. The prevalence of ABD was significantly higher in patients with PTH
      below 50 pg/ml than in patients with PTH above 50 pg/ml (p < 0.05). In 69% of
      children with NB the iPTH level was between 50 and 150 pg/ml. Most HP cases (75%)
      were diagnosed in patients with iPTH above 200 pg/ml. A high correlation between
      BFR and iPTH, BFR and OC, AP levels was found. CONCLUSION: The biochemical
      markers of bone turnover have only limited value in the differentiation of renal
      osteodystrophy types.

PMID- 10914960
TI  - A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3)
      causes non-syndromic craniosynostosis.
AB  - A unique Pro250Arg mutation in fibroblast growth factor receptor 3 (FGFR3) was
      recently found in patients with non-syndromic craniosynostosis. We studied 18
      Taiwan Chinese patients with various types of craniosynostosis to evaluate if
      this mutation is also prevalent in the Chinese population. Genomic DNA was
      analysed by polymerase chain reaction based restriction analysis and direct
      sequencing to identify the Pro250Arg mutation in FGFR3. Five (28%) of 18 probands
      were heterozygous for the Pro250Arg mutation. Only those patients with coronal
      synostosis carried this mutation. CONCLUSION: Our findings suggest that all
      patients with coronal synostosis should be examined for this unique mutation.

PMID- 10914961
TI  - Erythropoietic activity and soluble transferrin receptor level in neonates and
      maternal blood.
AB  - Serum transferrin receptor (sTfR) concentration reflects functional iron status
      and erythropoietic activity. The aims of this study were to examine gender
      differences of erythropoiesis in newborns and to evaluate the influences of
      maternal anaemia or iron deficiency on foetal cord blood parameters for iron
      status and sTfR. In total, 527 newborns and their mothers were examined.
      Reticulocytes were analysed by flow cytometry and sTfR was measured by an
      immunoenzymometric method. There were no sex differences in haematological or
      iron parameters. However, the reticulocyte maturity index (RMI) of male neonates
      was 37.45%, significantly higher than the 26.81% in female neonates (p <0.01).
      The high fluorescence reticulocytes (HFR) and middle fluorescence reticulocytes
      (MFR) of male neonates were 4.91% and 22.36%, respectively, while those of female
      neonates were 3.31% and 17.83%, respectively (p < 0.01 for each gender). The sTfR
      concentrations of male and female neonates were 6.27 mg/l and 5.09 mg/l,
      respectively (p < 0.01). Values for serum iron, ferritin and reticulocyte
      subpopulations were significantly lower in the newborns of anaemic mothers.
      However, newborns of iron-deficient mothers showed no differences in iron
      parameters from those of non-iron-deficient mothers. CONCLUSIONS: The higher
      values of RMI and sTfR observed in male neonates indicate that erythropoietic
      activity is higher in this group. Iron transport to the foetus appears to be
      independent of maternal iron deficiency. However, iron transport and
      erythropoiesis in newborns seems to decline from the time that the mothers
      acquire frank iron deficiency anaemia.

PMID- 10914962
TI  - Serum total magnesium and ionized calcium concentrations in asphyxiated term
      newborn infants with hypoxic-ischaemic encephalopathy.
AB  - Total magnesium, ionized calcium, potassium and sodium concentrations in mixed
      umbilical cord blood and venous blood serum at a median (min.-max.) age of 33 h
      (24-48 h) were assessed colorimetrically in 46 asphyxiated and 35 healthy term
      infants. Asphyxiated infants without any signs or with signs of mild hypoxic
      ischaemic encephalopathy (HIE) had significantly higher, and infants with severe
      HIE lower umbilical cord blood serum total magnesium (mean (95%CI) 0.81 (0.75
      0.87) mmol/l and 0.64 (0.47-0.87) mmol/l, respectively, p < 0.05) compared with
      the control group (0.72 (0.69-0.76)mmol/l). An increase in serum total magnesium
      in spite of normalized acid-base status in asphyxiated infants suffering from
      severe HIE compared with the control group infants was found by the second day of
      life (0.97 (0.87-1.07) mmol/l and 0.86 (0.81-0.9) mmol/l, respectively, p <
      0.05). At the age of 24-48 h hypermagnesaemia (>2 SD) was discovered in 36%,
      hyponatremia (<2 SD) in 38%, and hypocalcaemia (<2 SD) in 23% of asphyxiated
      infants. Derangements (>2 SD) in at least two electrolytes by the second day of
      life were significantly associated with poor outcome. CONCLUSIONS: Magnesium,
      calcium and sodium derangements are a frequent finding in asphyxiated infants,
      and these abnormalities are significantly associated with poor outcome. For a
      better outcome prediction, the routine determination of magnesium in addition to
      other electrolytes in asphyxiated infants is recommended.

PMID- 10914963
TI  - Neonatal escherichia coli infections: concerns regarding resistance to current
      therapy.
AB  - Currently recommended antibiotic treatment of suspected neonatal sepsis is
      ampicillin and an aminoglycoside. Recently, we observed increasing ampicillin and
      gentamicin resistance in strains of Escherichia coli isolated from neonates at
      our institution. We therefore reviewed clinical and laboratory records of all
      neonates with systemic infection, hospitalized from 1994 through 1998, from whom
      E. coli was isolated from blood and/or cerebrospinal fluid. The influence of
      perinatal variables (e.g. rupture of foetal membranes > 24h, group B
      Streptococcus (GBS) colonization, urinary tract infection during pregnancy and
      the use of antepartum and/or intrapartum antibiotics), and neonatal variables
      (e.g. gestational age, age at onset of sepsis (early: < or = 72 h, late: >72 h),
      number of E. coli septic recurrences, and associated underlying medical and/or
      surgical conditions) on antimicrobial susceptibilities of invasive E. coli
      isolates was studied. Twenty-three neonates with invasive E. coli infection were
      identified; most [19 (83%)] presented as late-onset sepsis (LOS). Ampicillin
      resistant E. coli were isolated in 75% and 53% of neonates in the early- and late
      onset groups, respectively. Gentamicin resistance was found in 50% of early-onset
      sepsis (EOS) isolates compared with 16% in the late-onset group. Isolates from
      two neonates with EOS were resistant to both ampicillin and gentamicin. One
      neonate with EOS and three with LOS had recurrent E. coli sepsis; all isolates
      were ampicillin-resistant and one was gentamicin-resistant. All these neonates
      were initially treated with ampicillin and gentamicin. Both groups had associated
      underlying medical and/or surgical conditions (50% early-onset, 47% late-onset).
      Maternal GBS colonization occurred in 2 (50%) versus 3 (16%) of EOS and LOS
      cases, respectively. All GBS colonized women received intrapartum ampicillin
      prior to delivery. CONCLUSIONS: Ampicillin and gentamicin resistance is emerging
      in neonatal E. coli isolates from invasive infection. Current- empiric management
      of neonatal sepsis requires re-evaluation given changing antimicrobial
      susceptibilities.

PMID- 10914964
TI  - Clinical and laboratory impact of coagulase-negative staphylococci bacteremia in
      preterm infants.
AB  - A retrospective evaluation of the clinical and laboratory impact of coagulase
      negative staphylococci (CONS) bacteremia in preterm infants was carried out. The
      study population included all preterm infants (n = 31) in whom two or more blood
      cultures were positive for CONS within a period of 4 d, with negative blood
      cultures 1 wk before and 1 wk after the CONS bacteremia. Clinical manifestations
      and the results of laboratory tests 7 d before and after the positive blood
      cultures, and on the first day of sepsis, were recorded and compared. During CONS
      bacteremia, the infants demonstrated apnoea and bradycardia (88%) and a need for
      oxygen (59%) and ventilatory support (69%). Significant laboratory findings were
      leukopenia below 5,000 cells/mm3 (12%), leukocytosis above 30,000 cells/mm3
      (39%), and thrombocytopenia below 150,000/mm3 (25%). These clinical and
      laboratory manifestations differed significantly during the bacteremia infection
      compared with the week before and after. CONCLUSION: CONS bacteremia is a
      clinically significant infection in preterm infants, causing episodes of apnoea
      and bradycardia, and a need for ventilatory support.

PMID- 10914965
TI  - Investigation of prolonged neonatal jaundice.
AB  - Jaundice persisting beyond 14 d of age (prolonged jaundice) can be a sign of
      serious underlying liver disease. Protocols for investigating prolonged jaundice
      vary in complexity and the yield from screening has not been assessed. In order
      to address these issues, we carried out a prospective study of term infants
      referred to our neonatal unit with prolonged jaundice over an 18 mo period.
      Infants were examined by a paediatrician and had the following investigations: a
      total and conjugated serum bilirubin, liver function tests, full blood count,
      packed cell volume, group and Coombs' test, thyroid function tests, glucose-6
      phosphate dehydrogenase levels and urine for culture. One-hundred-and-fifty-four
      infants were referred with prolonged jaundice out of 7,139 live births during the
      study period. Nine infants were referred to other paediatric specialties. One
      infant had a conjugated hyperbilirubinaemia, giving an incidence of conjugated
      hyperbilirubinaemia of 0.14 per 1,000 live births. Diagnoses included: giant cell
      hepatitis (n = 1), hepatoblastoma (n = 1), trisomy 9p (n = 1), urinary tract
      infections (n = 2), glucose-6-phosphate dehydrogenase deficiency (n = 3) and
      failure to regain birthweight (n = 1). CONCLUSIONS: In conclusion, a large number
      of infants referred to hospital for prolonged jaundice screening had detectable
      problems. The number of investigations may safely be reduced to: a total and
      conjugated bilirubin, packed cell volume, glucose-6-phosphate dehydrogenase level
      (where appropriate), a urine for culture and inspection of a recent stool sample
      for bile pigmentation. Clinical examination by a paediatrician has a vital role
      in the screening process.

PMID- 10914966
TI  - Attenuated endothelin- mRNA expression with endothelin- receptor blockade during
      hypoxaemia and reoxygenation in newborn piglets.
AB  - We investigated the cause of decreased plasma endothelin-1 (ET-1) during
      hypoxaemia and reoxygenation in newborn piglets subjected to simultaneous
      blocking of the ET-1 receptors. Changes in plasma ET-1 and prepro-ET-1 mRNA
      expression in the main pulmonary artery and the left lower lobe in the lung were
      studied in 1-2-d-old piglets. Ten minutes prior to hypoxaemia, the hypoxaemia
      group (n = 10) was given saline, two groups (both n = 9) were given 1 and 5 mg/kg
      i.v. SB 217242 (an ET-1 receptor antagonist). Two groups served as normoxic
      controls, with and without SB 217242 5 mg/kg i.v. Hypoxaemia was induced by
      ventilating with 8% O2 until base excess was <-20 mmol/l or mean arterial blood
      pressure was <20 mmHg. Reoxygenation was performed for 2 h with room air. During
      hypoxaemia, plasma ET-1 decreased in the hypoxaemia group, remained unchanged in
      the 1-mg group and increased in the 5-mg group. At the end of reoxygenation,
      plasma ET-1 was above baseline in the 1-mg and 5-mg groups. In the pulmonary
      artery, the hypoxaemia group showed 2- to 5-fold higher prepro-ET- 1 mRNA
      expression compared to all the other groups (p < 0.05). There were trends for
      higher prepro-ET-1 mRNA expression in pulmonary tissue in the hypoxaemia group
      compared to the two receptor-blocking groups (p < 0.07). CONCLUSIONS: We conclude
      that hypoxaemia and reoxygenation increase prepro-ET-1 mRNA expression in the
      pulmonary artery in newborn piglets. These observations suggest that the half
      life of ET-1 is decreased during hypoxaemia and reoxygenation in newborn piglets.

PMID- 10914967
TI  - Birthweight and social deprivation: influences on serum lipids and fibrinogen.
AB  - Epidemiological studies have shown that adults with low birthweight have a higher
      risk of cardiovascular disease and some others have shown that they have a less
      favourable serum lipid and lipoprotein profile. If cholesterol metabolism were
      programmed in utero, we would expect to see an influence of birthweight on blood
      lipids in children. In 422 children aged 11-15 y in Middlesborough, Cleveland,
      UK, we investigated the association between birthweight and serum lipids and
      plasma fibrinogen. We also investigated the influence of childhood social
      deprivation, measured using the Townsend deprivation index, on these measures.
      CONCLUSIONS: We found a significant inverse association between birthweight and
      serum triglyceride level, but not with other serum lipid levels. From a
      regression model we estimate that triglyceride rose by 1.1 mmol l(-1) kg(-1) fall
      in birthweight after adjustment for sex, current age and weight. Findings were
      similar in boys and girls separately. This could contribute to the observed
      inverse association between birthweight and cardiovascular mortality. Social
      deprivation was associated with higher fibrinogen, but not lipid levels. Our data
      highlight the importance of considering influences throughout the life course on
      adult disease.

PMID- 10914968
TI  - Can parents predict the severity of childhood obstructive sleep apnoea?
AB  - OBJECTIVE: To determine whether parents' observations can be used to predict the
      severity of the obstructive sleep apnoea syndrome (OSAS) in children. STUDY
      DESIGN: Sixty-five children with OSAS diagnosed by overnight polysomnography were
      consecutively recruited and classified as having severe or non-severe OSAS
      according to the obstructive apnoea index (OAI) and the oxygen saturation
      measured by pulse oximetry (SpO2) nadir. Parents were asked to complete a
      questionnaire about the child's breathing difficulties at night. RESULTS: Twenty
      eight patients were classified as severe OSAS and 37 as non-severe OSAS. There
      were no differences between the two groups with respect to age, sex or body mass
      index. Male to female ratio was 5:1. Parents of children with severe OSAS more
      frequently reported observed cyanosis (35 vs 8%; p=0.02); obstructive apnoea (60
      vs 35%; p = 0.04); snoring extremely loudly (52 vs 22%; p = 0.01); shaking the
      child (64 vs 35%; p = 0.02); watching the child during sleep and being afraid of
      apnoea (85 vs 60%; p = 0.03). However, neither any single nor combinations of
      observations showed high values for both sensitivity and specificity.
      CONCLUSIONS: Although some parents' observations are more frequently reported in
      children with severe OSAS, neither any single nor combinations of observations
      accurately predict the severity of OSAS. Polysomnography is still needed to
      determine the severity of obstruction.

PMID- 10914969
TI  - Visual analogue scale for the perceived influence of exertion and
      movements/positions on low back problems in surveys of adolescents.
AB  - The test-retest reproducibility of visual analogue scales for the perceived
      influence of exertion and movements/positions on low back problems in adolescents
      was investigated. The study was performed on 61 adolescents with low back
      problems. Item completion, median score, interquartile range and weighted kappa
      were calculated. Results showed that visual analogue scales produce repeatable
      information for all items tested (weighted kappa: 0.59-0.83), except for the
      influence of pulling materials on back problems (0.45). CONCLUSION: The results
      of this study suggest that adolescents, aged 16-18 y, can reproduce their visual
      analogue scores.

PMID- 10914970
TI  - Coping of parents and siblings with the death of a child with cancer: death after
      terminal care compared with death during active anticancer therapy.
AB  - Seventy pediatric patients with cancer treated at the Hospital for Children and
      Adolescents, University of Helsinki, Finland, died while in terminal care and 30
      children of therapy-related complications during active anticancer therapy in the
      period 1987-92. The purpose of this study was to compare these groups and
      characterize the main problems of the families during the mourning process. The
      method of evaluation was a structured interview of every parent separately.
      Parents of 60/70 children after terminal care, and parents of 26/30 children who
      died during active anticancer therapy, were interviewed. Unexpectedly,
      differences were minimal between families who lost a child after terminal care
      and those whose child died during active anticancer therapy. Parents reported
      physical and/or mental problems with similar frequency (39% and 34%); average
      self-reported recovery times were similar (14 and 16 mo); return to work was
      similar in both groups, 70% returning doing so within 1 mo. However, pronounced
      differences were observed between the mothers and the fathers; the mothers
      requiring longer recovery times and returning to work later. Of the siblings, 18%
      in the terminal care group had problems compared with 32% in the active therapy
      group. These included fear, behavioral problems, problems with friends and school
      related problems. In conclusion, when a child with cancer dies, the ability of
      the respective families to cope does not seem to differ whether the child dies
      after terminal care or during active anticancer therapy. The inevitable loss of
      the child is the major event. Most parents and siblings have the potential and
      ability to recover normally after the death of a child, although they will never
      be completely the same.

PMID- 10914971
TI  - Organized violence and mental health of refugee children in exile: a six-year
      follow-up.
AB  - In an earlier study we described a high rate of poor mental health in 63 refugee
      children from Chile and the Middle East during the first 18 mo of exile. In this
      follow-up study the mental health of 49 of these children is described in parent,
      teacher and child interviews 6-7 y after settlement in Sweden. The level of poor
      mental health in parent interviews has improved from 47% 18 mo after settlement
      to 22% (p < 0.01 in paired t-test) at follow-up. CONCLUSIONS: Eighteen percent of
      34 children still in primary school were judged by their teachers to show deviant
      behaviour in the classroom. Three children were found to suffer from either
      reexperience or avoidance of painful memories, whereas only one neurologically
      impaired child fulfilled the criteria of PTSD according to DSM-IV. Recent stress
      in the family sphere and exposure to acts of organized violence in the country of
      origin are identified as the major determinants of poor mental health.

PMID- 10914973
TI  - Infantile hypophosphatasia: disappointing results of treatment.

PMID- 10914972
TI  - Kangaroo care improves post-extubation cardiorespiratory parameters in infants
      after open heart surgery.
AB  - The aim of this investigation was to study whether kangaroo care could be helpful
      in full-term infants subjected to cardiac postoperative intensive care during the
      early post-extubation hours. Kangaroo care was performed at 2-h intervals in the
      first 12 h after extubation in 5 male infants and assessed by cardiorespiratory
      parameters. Results showed that, during kangaroo care, heart rate (123 +/- 4 vs
      128 +/- 5 bpm), respiratory frequency (43 +/- 3 vs 51 +/- 5 breath pm),
      transcutaneous carbon dioxide (46 +/- 2 vs 50 +/- 4 mmHg) and central venous
      pressure (11 +/- 0.8 vs 12 +/- 1.2 mmHg) significantly decreased (p <0.05 for
      all), while oxygen saturation (78 +/- 6 vs 74 5 mmHg) and transcutaneous oxygen
      pressure increased (42 +/- 2 vs 38 +/- 3 mmHg) (p < 0.05 for all). CONCLUSION: We
      conclude that kangaroo care might be a useful technique contributing to
      stabilization of the cardiorespiratory status in postoperative paediatric cardiac
      intensive care.

PMID- 10914974
TI  - A very rare cause of intestinal pseudoobstruction: familial visceral myopathy
      type IV.

PMID- 10914975
TI  - Antley-Bixler syndrome associated with Arnold-Chiari malformation.

PMID- 10914976
TI  - Sturge-Weber syndrome without facial nevus: a case report and review of the
      literature.

PMID- 10914977
TI  - Temporal association of chickenpox and meningococcal disease in children: a
      report of three cases.

PMID- 10914978
TI  - Sources of plasma leptin in infants after feeding.

PMID- 10914979
TI  - Language problems in children at risk neonatally.

PMID- 10914980
TI  - Transepidermal water loss in 24 and 25 weeks gestational age infants.

PMID- 10914981
TI  - Is prevention of coeliac disease possible?

PMID- 10914982
TI  - A case associated with Walker Warburg syndrome phenotype and homozygous
      pericentric inversion 9: coincidental finding or aetiological factor?

PMID- 10914983
TI  - Pathophysiology and diagnosis of primary hyperparathyroidism--strategy for
      asymptomatic primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia due to
      excessive secretion of PTH, is usually associated with hypophosphatemia and
      elevated serum chloride. Although PHPT was often complicated by renal stone
      disease and osteitis fibrosa in the past, routine screening of serum calcium (Ca)
      and development of sophisticated assay of parathyroid hormone have contributed to
      earlier detection of asymptomatic PHPT (APHPT). The proportion of APHPT patients,
      who have a mild elevation of serum Ca levels, usually within 1.0 mg/dL above the
      upper limit of normal, rose from 10-20% to approximately 45% of all PHPT patients
      in 1990-1995 in our clinic. Although it has been reported that the prevalence of
      PHPT is about 0.1% of the American population, the prevalence of PHPT appears to
      be far less in the Japanese population. Determination of a strategy for the
      increasing number of APHPT patients, is a pressing need but has yet to be
      accomplished. Treatment with bone antiresorptive drugs has met with some success,
      although the long-term efficacy of this treatment is not clear. The therapeutic
      effects of Ca-sensing receptor agonists appear promising.

PMID- 10914984
TI  - Parathyroid imaging with technetium-99m sestamibi.
AB  - The accurate identification of the location of hyperfunctioning parathyroid
      nodules is essential to the effective surgical treatment of hyperparathyroidism.
      Radionuclide imaging has played an important role in the detection of
      pathological parathyroid nodules. Sestamibi is a new radiopharmaceutical with a
      good affinity for parathyroid tissue that images hyperfunctioning parathyroid
      lesions as hot nodules. The double-phase protocol with early (ten minutes) and
      delayed (120 minutes) imaging is effective fordetecting the parathyroid lesions.
      The use of a pinhole collimator improves the sensitivity, but attention should be
      paid to the ectopic gland. Most lesions heavier than 250 mg could be detected
      with this scintigraphy, but the detectability of hyperplastic glands is inferior
      to that of adenomas. A sestamibi scan is better for the detection of ectopic
      lesions and recurrent disease than ultrasonography, and its detectability is also
      superior to other radionuclide tests such as tetrofosimin scanning and the
      subtraction technique using thallium-201 and Tc-99m pertechnetate images. The
      application of sestamibi to radionuclide-guided parathyroidectomy has been
      studied with encouraging results. Sestamibi can also be used for the evaluation
      of autotransplanted glands.

PMID- 10914985
TI  - Surgical management of primary hyperparathyroidixsm.
AB  - Bilateral neck explorations for primary hyperparathyroidism have a high cure rate
      (> 95%) and a low rate of morbidity when performed by experienced surgeons.
      Despite this. there have been many efforts to minimize the procedure in terms of
      length and region of incision. cost, extent of exploration, and length of
      hospital stay, while maintaining an excellent outcome. A renewed interest in
      unilateral neck exploration for primary hyperparathyroidism developed upon the
      introduction of sestamibi scintigrams as a new preoperative localization
      technique. The localization of adenomas using this technique was much more
      accurate than that of previous localization studies. allowing unilateral
      procedures to become feasible. Several surgeons have advocated a unilateral
      approach using preoperative sestamibi scanning. Sestamibi-guided
      parathyroidectomies enable parathyroidectomies to be performed much more rapidly
      through a significantly less invasive dissection. This procedure results in a
      very high cure rate with fewer complications, a smaller neck incision, and less
      use of post-operative narcotics. In patients with hyperparathyroidism. the
      intraoperative quick PTH assay allows the success of the procedure to be
      predicted intraoperatively. The intraoperative quick PTH assay is not only
      helpful in standard initial parathyroidectomies, but also improves the success
      rate of reoperative procedures. Its use is mandatory in all minimally invasive
      procedures. Initial reports regarding this innovation have been extremely
      positive. Nevertheless, some questions have been raised regarding the accuracy
      and utility of this procedure. Endoscopic parathyroidectomies offer several
      opportunities for innovation. Various approaches have been shown to be
      technically feasible, such as endoscopic procedures that rely on CO, insufflation
      to create a working space or video-assisted procedures in which the working space
      is maintained through conventional external retraction.

PMID- 10914986
TI  - Familial hyperparathyroidism.
AB  - Familial hyperparathyroidism (HPT) is a hereditary disease in which HPT is
      transmitted in an autosomal dominant fashion. It includes a variety of diseases:
      multiple endocrine neoplasia (MEN) type 1 and type 2, and familial isolated
      hyperparathyroidism (FIHPT). We screened for MEN 1 mutations by direct nucleotide
      sequencing of all protein-coding regions and identified the germline mutations of
      the MEN 1 gene in two families with familial HPT. Patients with FIHPT have
      multiple abnormal parathyroid glands and are prone to both recurrent and
      persistent HPT. They frequently present with profound hypercalcemia, in contrast
      to patients with MEN-associated HPT or sporadic HPT. We recommend subtotal or
      total parathyroidectomy plus autotransplantation in patients with MEN-associated
      HPT and patients with FIHPT. Because parathyroid remains or supernumerary glands
      are often present in the thymus or perithymic tissue, we advocate routine
      bilateral dissection of the central zone with bilateral cervical thymectomy.

PMID- 10914987
TI  - Management of renal hyperparathyroidism.
AB  - Histopathological and pathophysiological investigations including the genetic
      approach have been contributing to management of renal hyperparathyroidism (HPT).
      In renal failure, parathyroid glands initially proliferate diffusely and
      polyclonally, and then are transformed to monoclonal nodular hyperplasia with
      aggressive growth potential and diminished expression of both the vitamin D
      receptor and calcium-sensing receptor. When more than one parathyroid gland
      progresses to nodular hyperplasia, HPT is refractory to medical treatment. To
      prevent advanced renal HPT, progression to nodular hyperplasia should be avoided.
      Control of hyperphosphatemia is very important to prevent advanced renal HPT, but
      it is usually difficult. Administration of vitamin D metabolites constitutes the
      most promising form of prophylaxis and should be performed with monitoring of the
      PTH level to avoid adynamic bone disease. Calcitriol pulse therapy is effective
      for advanced renal HPT; however, when parathyroid glands progress to nodular
      hyperplasia, surgical treatment should be considered. Measuring parathyroid
      volume by ultrasonography is useful for detecting nodular glands and deciding
      treatment options. Parathyroidectomy (PTx) is an effective treatment for advanced
      renal HPT. However, the timing of the operation is important, because the
      improvement of skeletal deformity and vessel calcification inducing high
      mortality risk cannot be expected even after successful surgery. Total PTx with
      forearm autograft is a suitable procedure for renal HPT. Recently. selective
      percutaneous ethanol injection therapy has been adopted as an alternative
      treatment to PTx, and new vitamin D analogues, phosphate binders without calcium,
      and calcimimetics have been developed as new options for management of renal HPT.

PMID- 10914988
TI  - Parathyroid hormone-related peptide and bone: pathological and physiological
      aspects.
AB  - Parathyroid hormone-related peptide (PTHrP) was initially discovered as a tumor
      derived systemic factor which causes humoral hypercalcemia of malignancy. When
      overproduced and secreted by tumor cells, PTHrP acts on target organs such as
      bone and kidney to cause hypercalcemia through its 'PTH-like effects'. The
      hypercalcemic effects of PTHrP are attributed to its N-terminal portion (1-36)
      which shows a limited homology with PTH and is able to bind to the common
      PTH/PTHrP receptor. In contrast to such pathological effects as a humoral factor,
      PTHrP is now recognized as a locally active cytokine produced by a variety of
      tissues and cell types. Gene knockout experiments have revealed critical roles
      for PTHrP in a wide spectrum of physiological processes including chondrogenesis.
      It also significantly contributes to various pathological processes such as tumor
      metastasis to bone and bone destruction in arthropathies, acting as a bone
      resorbing cytokine. Consistent with its divergent roles, regulation of PTHrP
      expression as well as its mode of action seems to be much more complex than its
      hormonal counterpart, PTH. In this article, we will briefly review the recent
      progress in our understanding of both physiological and pathological aspects of
      PTHrP biology, with a particular focus on its roles as a bone cytokine.

PMID- 10914989
TI  - Surgical pathology of hyperparathyroidism.

PMID- 10914990
TI  - Gene diagnosis and clinical management of multiple endocrine neoplasia type 1
      (MEN1).
AB  - Identification of the MEN1 gene as a disease gene for multiple endocrine
      neoplasia type 1 (MEN1) has made it possible to predict whether a family member
      of an MEN1 patient will suffer from the same disease. MEN1 mutations have been
      found in almost all cases with familial MEN 1, but in fewer cases with sporadic
      MEN1. We analyzed MEN1 mutations in the largest number of Japanese MEN1 patients,
      17 families and 21 sporadic cases, and found 54 MEN1 mutant carriers and 30 non
      carriers. Furthermore, we identified a MEN1 phenocopy: GH-secreting pituitary
      tumor and primary hyperparathyroidism, which develops at older ages. In this
      article, we discuss how to utilize MEN1 gene diagnostics for the clinical
      management of MEN 1 patients and MEN1 mutation carriers.

PMID- 10914991
TI  - Endoscopic parathyroidectomy.
AB  - During the last three years, minimally invasive procedures have been adopted for
      the surgical treatment of primary hyperparathyroidism, because preoperative
      localization studies such as a high-resolution ultrasonography and sestamibi
      scintigraphy. guidance by intraoperative scans and the use of a quick,
      intraoperative PTH assay, have improved. Therefore, endoscopic parathyroidectomy
      can be performed for patients with primary hyperparathyroidism. The endoscopic
      procedures range from the 'pure' endoscopic approach characterized by constant
      gas insufflation and video-assisted gasless techniques. Then, we regard the
      cosmetic result as important, and adopted the 'pure endoscopic approach because a
      small incision can be made far from the neck region. We report our technique with
      no scars in the neck region for endoscopic unilateral neck exploration with
      primary hyperparathyroidism by an axillary approach and for endoscopic bilateral
      neck exploration with renal hyperparathyroidism by an anterior chest approach.

PMID- 10914992
TI  - Parathyroidectomy at ito hospital: a review of a thyroid clinic in Japan.
AB  - We primarily describe surgical methods and short-stay surgery, which has been
      recently attracting interest in Japan, in relation to the diagnosis and treatment
      of parathyroid disease at a special hospital for thyroid diseases. There is a
      controversy in regard to surgical methods for primary hyperparathyroidism (PHPT),
      whether it is sufficient to examine only one side or all four glands should be
      checked. At our hospital, we selected one of the following three different
      approaches depending on the case: where the lesion was excised after checking all
      four glands on both sides (Method A), where the lesion was excised after checking
      two glands by examining one side (Method B), and where the lesion of one gland
      was directly excised (Method C). A review of the initial operations for 185 cases
      of PHPT treated at our hospital over 18 years revealed that the patients who
      underwent Methods B and C under local anesthesia had developed no complications
      and their long-term postoperative outcome was also favorable. In the future we
      also intend to adopt the unilateral approach aggressively under local anesthesia
      and perform short-stay surgery in cases which pathological parathyroid glands
      have been discovered by preoperative localization.

PMID- 10914993
TI  - Long-term prognosis of parathyroid function after successful percutaneous ethanol
      injection therapy (PEIT) guided by color Doppler flow mapping in chronic dialysis
      patients.
AB  - Secondary hyperparathyroidism (2 HPT) is a representative disease of dialysis
      osteopathy, with the lesion that makes fibrous osteitis and the parathyroid
      hyperplasia by the hyper secretion of parathyroid hormone (PTH). This research
      examines the usefulness of selective percutaneous ethanol injection therapy
      (PEIT) of parathyroid glands in order to treat and control for 2 HPT. PEIT was
      performed in 46 patients resistant to calcitriol pulse therapy and all glands
      larger than 5 mm in diameter were destroyed by ethanol guided by power Doppler
      flow mapping. Serum intact-PTH (iPTH) levels fell from 633.3 +/- 359.9 to 226.3
      +/- 204.7 pg/mL at three weeks and were maintained at 289.9 +/- 222.4 pg/mL at
      one year after PEIT. Total alkaline phosphatase activity fell from 384.9 +/-
      160.1 to 234.0 +/- 110.5 IU/L at one year after PEIT. In 19 patients, i-PTH
      levels fell into relative hypoparathyroidism (iPTH < 160 pg/mL) at three weeks
      after PEIT: however, they recovered at one year after PEIT (191.1 +/- 29.6
      pg/mL). In total, parathyroid function was maintained at optimal range (160 <
      iPTH < 360 pg/mL) in 80.4% of patients at one year after PEIT with appropriate
      medical therapy. As for the complications, recurrent nerve palsy was observed in
      only one patient, but was reversible. In conclusion, selective PEIT appears to be
      able to control appropriate parathyroid function and to be the method of choice
      to treat 2 HPT prior to parathyroidectomy.

PMID- 10914994
TI  - Microcapsulated parathyroid tissue in vitro.
AB  - Ideally, microcapsules will make it possible to transplant parathyroid tissue for
      allo- and xenotransplantation in hypoparathyroid patients. In this study,
      parathyroid tissues capsulated by polyelectrolyte complex were evaluated in
      vitro. Hormone secretion ability was significantly (P < 0.001) greater in
      sediment than in supernatant. There was no difference in hormone secretion
      ability between the parathyroid tissue thawed at room temperature and the tissue
      thawed in a bath at 37 degrees C. Both non-capsulated and capsulated parathyroid
      tissues were incubated for three weeks. The ability of capsulated parathyroid to
      secrete hormones in vitro was reduced gradually and disappeared within three
      weeks. There are still several problems to be solved before the clinical
      application of parathyroid allotransplantation using microcapsulation.

PMID- 10914995
TI  - Clinical features of primary hyperparathyroidism: preoperative localization and
      parathyroidectory.
AB  - The introduction of the multichannel autoanalyser made measurement of serum
      calcium concentrations easier, and led to a dramatic change in clinical
      presentations. The reliable methods such as computed tomography (CT),
      ultrasonography (US) and magnetic resonance imaging (MRI) for preoperative
      localization of abnormal parathyroid glands has long been sought to increase the
      cure rate of surgical treatment. We report the clinical feature of primary
      hyperparathyroidism (PHPT). Patients were classified into four stages in
      chronological order. The early patients (the first stage, 1970-1979) were mainly
      diagnosed in the treatment of urolithiasis. Approximately 20% of patients in the
      second stage (1980-1986) were symptom-free, and hypercalcemia was detected by
      autoanalyzer. Patients in the third stage (1987-1993) underwent preoperative
      localization studies including CT. scintigraphy, ultrasonography and MRI. The
      recent patients (the fourth stage, 1993-1999) were mostly treated in the present
      hospital. In the first stage, PHPT was an uncommon metabolic disorder hat was
      typically associated with nephrolithiasis and was two to three times more common
      in men than in women. In the second, third and fourth stages, PHPT is a common
      and often symptomless endocrine disorder. The ratio of male to female is
      decreasing, because men are dominant in stone-formers. Four parathyroid glands
      were searched carefully in the first and second stages, and unilateral cervical
      exploration was performed in some preoperatively localized parathyroid glands in
      the third and fourth stages.

PMID- 10914996
TI  - Review of 41 patients operated on for primary hyperparathyroidism.
AB  - We reviewed 41 cases of operation for primary hyperparathyroidism (PHPT) in our
      institution between 1987 and 1999. The objective of this study was 1) to evaluate
      the sensitivity and positive predictive value of several localization studies for
      an enlarged parathyroid gland; 2) to determine whether a selective. unilateral
      exploration operation is safe; and 3) to investigate rates of coexisting
      malignancies of other organs. A total of 61 enlarged parathyroid glands (701 +/-
      131 mg wt) were removed, and the lesions consisted of 32 adenomas, two cancers,
      and seven hyperplasias. MIBI scintigraphy had both a high sensitivity (88.9%) and
      positive predictive value (88.9%) for localization of abnormal parathyroid glands
      and yielded better performance than the other techniques, including
      ultrasonography, CT scanning, and Tl-Tc scintigraphy. However, all of the
      localization techniques failed to detect enlarged glands (18/32 glands = 62.5%)
      in patients with multi-glandular parathyroid lesions. Initial operations with
      selective unilateral exploration of the neck were successful in 23 of 24 patients
      (95.8%). Operative failure was due to missing the second adenoma of a double
      adenoma. Malignant tumors were found in 11 patients (26.8%) previously treated or
      concurrently managed at the time of parathyroidectomy. There was a significant
      increase in serum-intact PTH level in patients with concurrent malignant tumors
      compared to patients who had no association of malignancies. In conclusion, 1) at
      least two preoperative localization tests, an MIBI scan and ultrasonography, are
      helpful in accurately localizing an abnormal parathyroid gland; 2) selective
      unilateral exploration is safe and desirable if the second ipsilateral gland is
      normal macroscopically; and 3) systematic examination for malignant tumors is
      necessary in PHPT patients before and after parathyroidectomy.

PMID- 10914997
TI  - Idiopathic hyperaldosteronism: analysis of aldosterone synthase gene.
AB  - We analyzed the CYP11B2, the gene encoding aldosterone synthase, in mononuclear
      leukocytes in eight patients with primary aldosteronism due to zona glomerulosa
      hyperplasia (idiopathic hyperaldosteronism) and compared the results with
      aldosterone-producing adenomas. In idiopathic hyperaldosteronism, aldosterone
      synthase activity was significantly increased in accordance with gene expression
      (P < 0.05), compared with aldosterone-producing adenomas. No genetic mutations
      were found in coding regions of DNA. The T (-344) C allele polymorphism was
      present in a similar frequency in the general population. In one patient with
      idiopathic hyperaldosteronism. de novo homozygous mutation in upstream of the 5'
      flanking region C (-463) T was detected, which cannot be explained by
      polymorphism. The pathophysiological significance of this mutation for
      aldosterone hypersecretion is not known. There were no mutations in the known
      promoter sequences for angiotensin II related cis-segments. Possible contribution
      of co-regulators for angiotensin 11-induced signalling pathway is discussed.

PMID- 10914998
TI  - Experimental parathyroid transplantation: human parathyroid grafts survived and
      functioned in mice treated with anti-CD4 monoclonal antibody.
AB  - Permanent hypoparathyroidism is one of the most difficult of all endocrine
      disorders to treat medically. To examine the possibility that xenotransplantation
      can be used to treat hypoparathyroidism, human parathyroid tissues were
      transplanted into mice. Human parathyroid tissue was taken from specimens excised
      from patients with hyperparathyroidism. Fresh human parathyroid tissue was
      implanted under kidney capsule of CBA (H2k) mice. Some mice were treated
      intraperitoneally with depleting anti-CD4 monoclonal antibody (mAb, YTA 3.1, 100
      microg/dose, days -1. 0. 1, 2, 3, and 5). Mice were killed 30 days after
      transplantation. Survival of parathyroid grafts was examined microscopically and
      human parathyroid hormone in serum was measured by ELISA. All parathyroid grafts
      survived under kidney capsule and human parathyroid hormone was strongly detected
      in serum (621 +/- 576 pg/mL) when recipients were treated with short-course
      treatment of anti-CD4 mAb. Conversely, no parathyroid tissue was seen
      microscopically in any recipient mice without anti-CD4 mAb treatment. Human
      parathyroid hormone was undetectable by ELISA in naive mice and mice transplanted
      with human parathyroid tissue without short-course treatment of anti-CD4 mAb.
      Xenogeneic human parathyroid tissue survived and functioned in mice treated with
      short-course treatment of anti-CD4 mAb.

PMID- 10914999
TI  - Clinical characteristics of primary aldosteronism: its prevalence and comparative
      studies on various causes of primary aldosteronism in Yokohama Rosai Hospital.
AB  - We studied 1,020 patients with hypertension visiting our outpatient clinic during
      a five-year period, from 1995 until 1999. Those subjects were screened by
      determining plasma renin activity (PRA) and plasma aldosterone concentration
      (PAC) after testing routine laboratory examinations in order to differentiate
      secondary hypertension from essential hypertension. All patients with low
      reninemic hypertension were examined by furosemide plus the upright test. This
      led to an increase in diagnoses of primary aldosteronism (PA) (confirmed by
      captopril-loading test). Our studies demonstrated that the incidence of PA is
      5.4%, and also that the plasma potassium level is not always beneficial for
      suspecting the presence of PA, because 28% of the patients with PA show only
      hypokalemia. We would like to emphasize that adrenal venous sampling plays a
      critical role in establishing the optimal management for patients with PA,
      because CT imaging is limited to detection of adrenal masses.

PMID- 10915000
TI  - Clinical aspects of hyperparathyroidism in Japanese multiple endocrine neoplasia
      type 1.
AB  - We describe here the clinical aspects of hyperparathyroidism (HP) in Japanese
      multiple endocrine neoplasia type 1 (MEN 1). The total number of MEN 1 patients
      was 37, and they originated from ten unrelated Japanese families. Nine of the ten
      families were proven to have heterozygous germline mutations of the MEN 1 gene.
      The incidence of HP, pituitary tumors, and pancreatic tumors in 37 MEN 1 patients
      was 91.9%, 32.4%, and 45.9%, respectively. The age-related penetrances of HP were
      50%, 79%, 84%, by 20, 30, and 40 years of age, respectively. Of these MEN 1
      patients, we used 28 individuals, diagnosed with HP at our hospitals, to study
      the clinical aspects of MEN 1-associated HP. The mean age was 40 years, and the
      mean was much lower in the sporadic (non-MEN 1) HP patients. The mean levels of
      calcium, phosphate, and intact PTH were 10.8 mg/dL, 2.3 mg/dL, and 178.0 pg/mL,
      respectively, and these were not different from those of sporadic HP patients.
      The levels of intact PTH were positively correlated with age, suggesting that HP
      may be progressive with time in MEN 1. The percentage of symptomatic HP was 36%
      in MEN 1, whereas it was 55% in sporadic HP patients. Although histopathological
      findings revealed that all four parathyroid glands were involved in hyperplasia,
      imaging studies showed an enlargement of only the single parathyroid gland in
      most patients. The combination of total parathyroidectomy and autoplantation
      succeeding in improving HP in MEN 1.

PMID- 10915001
TI  - Pre- and postoperative bone metabolism of primary hyperparathyroidism.
AB  - Primary hyperparathyroidism (PHPT) is a well-known indicator of severe bone loss.
      However, the recovery process of bone mineral density after surgery in PHPT
      patients is not sufficiently clear. We examined postoperative bone metabolism in
      24 PHPT patients. PATIENTS AND METHODS: Subjects were 24 patients with PHPT upon
      whom we performed parathyroidectomy in the Department of Surgery II, Fukushima
      Medical University. Mean age was 54.2 years and the male-to-female ratio was
      10:14; mean time of follow-up was 27.3 months. Patients were divided
      histopathologically into 16 adenomas and eight hyperplasias, and classified by
      heredity into seven familial (six, MEN 1; one, MEN 2) and 17 sporadic types. Bone
      mineral density was measured by dual energy X-ray absorptometry (DXA) and digital
      image processing (DIP). Age-matched values of these parameters were obtained.
      Serum bone metabolic parameters; ionized calcium (CaF), phosphorus, intact PTH
      (iPTH), c-PTH, ALP, osteocalcin (OC) and PTHrP were measured. RESULTS: PHPT
      patient preoperative bone mineral densities were significantly lower than those
      of healthy controls. Those by DIP method were lower than those by DXA. High CaF,
      iPTH, OC and ALP levels were indicated before surgery, but all parameters
      immediately became normal. Longitudinal bone mineral density changes of
      asymptomatic cases increased more than those of patients with renal stone and/or
      ostitis fibrosa. In adenoma cases, tumor weights were significantly inversely,
      which correlated with preoperative DIP bone density measurements. CONCLUSION:
      Preoperative PHPT patients showed decreased bone density; bone loss in
      symptomatic cases was especially prominent compared to asymptomatic cases. Most
      PHPT patients had not completed the BMD recovery after surgery, so even
      asymptomatic and mild PHPT patients should undergo parathyroidectomy to minimize
      irreversible bone loss.

PMID- 10915002
TI  - Bone metabolic analysis in patients with primary hyperparathyroidism.
AB  - Surgical treatment for primary hyperparathyroidism (PHPT) improves not only the
      calcium and phosphate metabolism but also the bone metabolism. This study was
      conducted to analyze the bone metabolism after PHPT operations. Bone mineral
      density (BMD) was measured by dual-photon absorptiometry in 50 patients before
      and after operation. Osteocalcin (OC) and alkaline-phosphatase activity (Alp) in
      serum were measured before and after surgery as markers of bone formation, and
      urinary deoxypiridinorine (DPD) as an index of osteoclast activity. The 50
      patients under study were 40 women (80%) and ten men (20%). Increases in BMD at
      the lumbar spine were remarkable at three months following operation. Slow but
      steady progress was made until six months, reaching a plateau thereafter. The
      increase in BMD of lumbar spine was approximately 10%. Urinary DPD was the most
      sensitive among the three bone metabolic markers. Although serum Alp and OC
      remained high after operation, urinary DPD was normalized earlier. The
      discrepancy of bone formation and resorption was shown after operation and this
      contributed to the increases in BMD in the first six months.

PMID- 10915003
TI  - Absence of somatic RET gene mutation in sporadic parathyroid tumors and
      hyperplasia secondary to uremia, and absence of somatic Men1 gene mutation in
      MEN2A-associated hyperplasia.
AB  - Germline mutations of the MEN1 gene are found in more than 85% of multiple
      endocrine neoplasia type 1 (MEN 1) patients, and germline mutations of the RET
      gene are found in more than 95% of multiple endocrine neoplasia type 2 (MEN2)
      patients. Parathyroid hyperplasia is seen in more than 90% of MEN 1 and about 15%
      of MEN2A patients. To date, somatic MEN1 mutations are reported in about 20% of
      sporadic parathyroid tumors. To elucidate the genetic basis of parathyroid tumor
      development, we examined somatic RET gene mutations in sporadic parathyroid
      tumors and hyperplasia secondary to uremia, and somatic MEN1 gene mutations in
      parathyroid hyperplasia from MEN2A patients. A total of 145 parathyroid tumors
      comprising 129 sporadic parathyroid tumors, 14 hyperplastic lesions secondary to
      uremia, and two hyperplastic lesions from MEN2A patients were examined. DNA was
      extracted from fresh frozen parathyroid tissue. Exons 2-10 of the MEN1 gene and
      exons 10 and 11 of the RET gene were sequenced. No somatic RET gene mutations
      were found in the 129 sporadic parathyroid tumors or 14 parathyroid hyperplastic
      lesions secondary to uremia. No somatic MEN1 gene mutations were found in the two
      parathyroid hyperplasia from MEN2A patients. These data suggest that RET gene
      mutation may not be involved in the development of sporadic parathyroid tumors
      and hyperplasia secondary to uremia and that MEN1 gene mutation may not be or is
      rarely associated with development of parathyroid hyperplasia in MEN2A patients.

PMID- 10915004
TI  - Treatment of osteopenia secondary to primary hyperparathyroidism.
AB  - A major challenge in the management of primary hyperparathyroidism (pHPT) is the
      decision regarding which patients should undergo parathyroidectomy (PTX).
      although the Consensus Development Conference of the National Institutes of
      Health (NIH) has proposed guidelines for the indication of surgery. We found that
      PTX brings about increases in radial and lumbar BMD values as high as 10% in
      virtually all pHPT patients including postmenopausal women and those without an
      indication for surgery based on NIH criteria. Serum alkaline phosphatase (ALP)
      level and the severity of cortical bone mass reduction are clinically useful for
      predicting the changes in lumbar BMD after PTX. The present findings provide a
      useful clue for the indication of surgery in pHPT, and seem to warrant a more
      extended indication than that of the NIH. We also described the recent progress
      in studies on calcium-sensing receptor (CaR), and discussed the possibility of
      bone mass recovery by medical treatment of pHPT with a newly introduced CaR
      agonist ('calcimimetics').

PMID- 10915005
TI  - Usefulness of quick intraoperative measurements of intact parathyroid hormone in
      the surgical management of hyperparathyroidism.
AB  - We investigated the use of quick measurement of intraoperative intact parathyroid
      hormone (I-PTH) to predict the outcome of parathyroidectomy. We examined
      intraoperative monitoring of I-PTH in 34 consecutive primary hyperparathyroidism
      (pHPT) patients operated on between April and December 1999. The average patient
      age was 56 +/- 13 years, and all but one were women. Four had a history of
      thyroidectomy. Blood samples were drawn before excision of enlarged parathyroid
      gland(s) and at 2, 5, 10, and 15 minutes afterward. Plasma I-PTH was measured by
      a two-site immunochemiluminometric assay. Twenty-three patients were shown to
      have single gland disease, and ten had multiglandular disease. All patients,
      except one, underwent successful parathyroidectomies. The plasma I-PTH value 15
      minutes after removal of enlarged gland(s) had dropped to 26 +/- 10% of pre
      excision I-PTH value. In one patient with a previous history of thyroidectomy for
      thyroid papillary cancer, no gland enlargement was found in the area where the
      lesion had been suggested by both ultrasonography and 99mTc sestamibi scanning.
      In this case, intraoperative measurements of I-PTH in the bilateral internal
      jugular veins identified an ectopic parathyroid tumor, which was successfully
      removed. We conclude that quick measurement of intraoperative I-PTH is a valuable
      tool for decision-making, especially for reoperative parathyroid surgery, for
      patients with previous history of thyroidectomy, and for patients in whom
      unilateral neck exploration or a single-gland approach is scheduled based upon
      preoperative localization.

PMID- 10915006
TI  - Pathophysiology and diagnosis of Cushing's syndrome.
AB  - Prolonged exposure of every tissue in the body to an excess of cortisol produces
      Cushing's syndrome. Endogenous causes of Cushing's syndrome are ACTH-dependent,
      including Cushing's disease, ectopic ACTH-producing tumors. CRH-producing tumors,
      and ACTH-independent Cushing's syndrome, including cortisol-producing adrenal
      benign or malignant tumors, and rare micronodular adrenal hyperplasia. In Japan
      the incidence of ACTH-dependent Cushing's syndrome due to endogenous causes is
      about 60%, in which autonomous pituitary ACTH secretion is responsible for 95%,
      and the rest are ectopic ACTH-producing tumors. Cortisol-secreting tumors are
      responsible for about 40% of endogenous causes, in which benign adenoma is 90%
      and adrenocortical carcinoma is 10%. The first step for the diagnosis of
      Cushing's syndrome is to demonstrate the presence of hypercortisolism
      biochemically by determining 24-hour urinary free cortisol excretion and low-dose
      dexamethasone suppression test. The next step is to identify the precise
      etiologic causes. To differentiate Cushing's syndrome, the most important
      procedures are dynamic endocrine tests to check the integrity of hypothalamic
      pituitary-adrenal function by high dose dexamethasone suppression test, CRH test
      arid measurement of steroid hormone profile. Imaging techniques can help to
      determine the etiology of Cushing's syndrome.

PMID- 10915007
TI  - Pathophysiology and diagnosis of primary aldosteronism.
AB  - The pathophysiology of primary aldosteronism still remains unknown. In mRNA and
      protein levels, overexpression of aldosterone synthase (P-450aldo) is recognized,
      although abnormalities and defects of DNA and its upper stream have not been
      detected. Several candidate genes responsible for pathogenesis of primary
      aldosteronism, such as renin, angiotensin receptor type II, etc., have been
      proposed, but no decisive genes have been found. A relatively reliable screening
      for hyperaldosteronism is a determination of the ratio of the plasma aldosterone
      level to the plasma renin activity. For differentiating several types of
      aldosteronisms, the simplest test is the response of plasma aldosterone to two
      hours in an upright posture: plasma aldosterone rises in most patients with
      idiopathic hyperaldosteronism. In contrast, in cases of autonomous aldosterone
      producing tumor, most patients show no response or even a decrease in plasma
      aldosterone concentration. The size and location of the aldosterone-producing
      adenoma are determined by using computed tomography.

PMID- 10915008
TI  - Current topics in pheochromocytoma.
AB  - Pheochromocytoma is the tumor that produces catecholamines and originates from
      chromaffin cells, which are differentiated from sympathoadrenal progenitor cells
      of neural crest under the influence of glucocorticoids. Genetic abnormalities of
      familial pheochromocytomas have elucidated oncogenic genetic bases of the tumor,
      including gene abnormalities of the RET proto-oncogene in multiple endocrine
      neoplasia type 2, VHL gene in von Hippel Lindau's disease or the NF1 gene in
      neurofibromatosis. Co-localization of various substances with catecholamines in
      the tumor, including neuropeptide Y, opioid peptides or adrenomedulOFF peptide
      elevating cAMP production, is recognized. The significance of these substances in
      modulating clinical features of pheochromocytomas is not fully understood.

PMID- 10915009
TI  - Non-surgical therapy of primary aldosteronism: transcatheter arterial infusion of
      ethanol into an aldosteronoma.
AB  - Primary aldosteronism due to an adrenocortical adenoma can be cured by ablation
      of the adenoma, which produces an excess of aldosterone (aldosteronoma). This has
      traditionally been performed by surgical removal of the adenoma. However, some
      patients with aldosteronomas refuse surgical removal. Therefore, we developed a
      therapeutic method to ablate an aldosteronoma by transcatheter arterial infusion
      of ethanol. This method ablated the aldosteronoma in 27 (82%) of 33 treated cases
      and produced no serious complications, and may be one of the therapeutic choices
      for aldosteronomas.

PMID- 10915010
TI  - Current management of incidentally discovered adrenal masses, with a review of
      Japanese literature.
AB  - It is becoming increasingly common to discover adrenal masses incidentally on
      radiologic imaging studies. We herein present our experience with 61 cases of
      incidentally discovered and surgically removed adrenal incidentalomas, including
      11 pheochromocytomas. Only four were adrenocortical carcinomas. A review of the
      literature, including Japanese journals, for the prevalence of incidentantally
      discovered adrenal mass, their differential diagnosis and management are
      discussed.

PMID- 10915011
TI  - Surgical management of Cushing's syndrome.
AB  - Patients with Cushing's syndrome (137 total) who underwent adrenalectomy from
      1957 through 1999 were reviewed for survival and complications. Of the 137
      patients, 83 had adrenocortical adenoma, 30 Cushing's disease, seven primary
      pigmented nodular adrenocortical disease (PPNAD), eight adrenocorticotropin
      (ACTH)-independent macronodular hyperplasia, five adrenocortical carcinoma, and
      four ectopic ACTH syndromes. Seventy-eight patients with adrenocortical adenoma
      are alive, and their survival rate was equal to the age-matched control
      population, when patients who died of postoperative complications were excluded.
      Of the patients with Cushing's disease, 20 are alive, and ten of 16 patients
      (63%) who were followed and evaluated, had skin pigmentation. Four of 16 patients
      (25%) developed Nelson's syndrome. Five PPNAD patients and six with ACTH
      independent macronodular hyperplasia are alive. All five adrenocortical carcinoma
      patients and four with ectopic ACTH syndrome died within two years after
      operation. The prognosis for patients with adrenocortical adenoma after
      unilateral adrenalectomy is excellent, though it is important to avoid operative
      complications. The rapid disappearance of signs and symptoms of glucocorticoid
      excess after total adrenalectomy is assured, and the prognosis is satisfactory
      under careful glucocorticoid replacement, making total adrenalectomy an
      alternative treatment for Cushing's disease.

PMID- 10915012
TI  - Surgical management of primary aldosteronism.
AB  - Adenoma is usually the etiology of primary aldosteronism, and we have also
      encountered 44 patients with adenoma since 1990. In this study. we examined
      surgical management of these patients. Conventional open surgery (supracostal
      flank incision) was performed in ten patients, and laparoscopic surgery in 34
      patients. When these two techniques were compared, the time required for
      laparoscopic surgery was significantly longer, although it tended to be
      considerably shortened in the last ten patients compared with that in the initial
      patients. However, regarding all the parameters of recovery in the last ten
      patients, laparoscopic surgery was superior to open surgery. Laparoscopic surgery
      seems to be the most appropriate surgery for patients with adrenal adenoma, which
      comprise the majority of patients with this disease.

PMID- 10915013
TI  - Surgical management of pheochromocytoma.
AB  - The early diagnosis and safe treatment of pheochromocytoma have become possible
      due to advances in preoperative imaging techniques and endocrine tests, as well
      as improvements in the control of blood pressure and hemodynamics before and
      during the operation using various drugs. This article outlines the use of
      meticulous surgical technique via various approaches for open surgery and gives a
      step-by-step description of the methods for laparoscopic surgery. Such techniques
      have made the excision of pheochromocytoma safe and easy, allowing hypertension
      to be surgically cured in these patients. Thus, pheochromocytoma is less likely
      to be fatal than before. However. it is necessary to follow these patients for a
      long period postoperatively because it is often difficult to distinguish benign
      from malignant tumors and recurrence has been reported even more than ten years
      postoperatively.

PMID- 10915014
TI  - Transperitoneal anterior laparoscopic adrenalectomy: the easiest technique.
AB  - Four laparoscopic methods have been developed to approach the adrenal gland:
      anterior or lateral transperitoneal approaches, and lateral or posterior
      retroperitoneal approaches. The advantages and disadvantages of these methods
      were reviewed during a workshop held by the Japanese Society of Endourology and
      ESWL in 1997. The transperitoneal anterior approach, when combined with a lateral
      approach for the left side, is the easiest for small adrenal tumors, and
      discloses the adrenal vein early in the procedure. For large tumors over 5 cm in
      diameter, the transperitoneal lateral approach is the most feasible bilaterally.
      Regardless of the methods of approach, laparoscopic adrenalectomy has already
      become the standard procedure for adrenal tumors, because it minimizes the
      operative morbidity and postoperative hospital stay.

PMID- 10915015
TI  - Laparoscopic adrenalectomy: posterior approach.
AB  - Adrenalectomy for benign adrenal diseases is currently performed by
      transperitoneal laparoscopy. The transperitoneal approach, however, invades the
      intraperitoneal cavity, and may cause injury to the abdominal organs. The
      posterior lumbar approach allows direct access to the main adrenal vascular
      supply before the gland is manipulated. Retroperitoneoscopic adrenalectomy by
      this approach is technically feasible and most effective as regard to the
      simplicity of vascular control. The operating time, perioperative morbidity and
      cost have been reduced with this approach.

PMID- 10915017
TI  - Recent advances in surgical pathology of adrenal incidentaloma.
AB  - Adrenal incidentaloma has recently increased in number because of the advances in
      radiologic diagnostic means. The clinical management and histopathological
      diagnosis of the resected adrenal mass has therefore become increasingly
      important. When evaluating the resected adrenal mass of the patients with adrenal
      incidentaloma, it is very important to evaluate the following aspects: 1) is the
      mass functional or not? 2) is the mass malignant or not? and 3) is the mass of
      adrenocortical origin or not? In this mini review, the recent advances in
      endocrine pathology of adrenal incidentaloma are briefly summarized, with
      emphasis on the three aspects above,

PMID- 10915016
TI  - Epidemiologic study of adrenal gland disorders in Japan.
AB  - A nationwide epidemiologic study of adrenal disorders was performed in Japan. To
      cover all the hospitals in Japan, the small-scale hospitals were selected at
      random, and all the large-scale hospitals were taken into the investigation.
      Disorders investigated in 1997 were relatively rare disorders, as follows:
      congenital deficiency of adrenal steroidogenic enzyme (deficiency of 21
      hydroxylase, 11beta-hydroxylase, 17alpha-hydroxylase, 3beta-hydroxysteroid
      dehydrogenase or 18-hydroxylase, and lipoid hyperplasia), congenital Addison's
      disease, pseudohypoaldosteronism, and 11beta-hydroxysteroid dehydrogenase
      deficiency. The total number of patients with congenital deficiency of adrenal
      steroidogenic enzyme from 1992 to 1996 was estimated as 1,462, and 87% of these
      patients suffered from 21-hydroxylase deficiency. The number of patients with
      congenital Addison's disease (1992-1996) was estimated at 103. About one-fifth of
      these patients were female. The causes for these female patients are not
      attributed to the abnormality of DAX-1 gene, because it causes adrenal
      insufficiency only in males. Almost all (97.8%) of the rare adrenal diseases were
      under treatment or under observation. The prognosis was thus found to be quite
      good, although continuation of the treatment was necessary. Disorders
      investigated in 1998 were relatively major diseases, as follows: primary
      aldosteronism, Cushing's syndrome, adrenal preclinical Cushing's syndrome,
      Addison's disease and pheochromocytoma. The total numbers of patients in Japan in
      1997 were estimated as 1,450 for primary aldosteronism, 1,250 for Cushing's
      syndrome, 290 for adrenal preclinical Cushing's syndrome, 660 for Addison's
      disease, and 1,030 for pheochromocytoma. In conclusion, for the first time, a
      reliable national estimation of the prevalence of disorders of adrenal hormones
      was conducted in this study.

PMID- 10915018
TI  - SSPG titer is a diagnostic marker for adrenocortical adenoma in patients with non
      functioning adrenal incidentaloma.
AB  - We analyzed insulin resistance-related clinical markers as well as imaging
      characteristics of adrenal masses in 11 patients with incidentally discovered
      adrenal tumors that were diagnosed as non-functioning according to the results of
      the 1 mg dexamethasone suppression test and then voluntarily resected. Histologic
      examination of the resected tumors revealed adrenocortical adenoma in eight
      patients, and non-cortical tumors: a myelolipoma. an endothelioma and an adrenal
      vascular cyst in three patients. All eight patients with adrenocortical adenoma
      exhibited insulin resistance as estimated by the steady-state plasma glucose
      (SSPG). The mean systolic blood pressure of the patients with adrenocortical
      adenoma was higher than that of the patients with non-cortical tumors, even
      though three of eight patients were normotensive. HOMA-R, EIRI on 75 g oGTT.
      diastolic blood pressure and serum triglyceride were not significantly different
      between the patients with adrenocortical adenomas and those with non-cortical
      tumors. Imaging characteristic such as tumor size, shape and heterogeneity in the
      mass did not distinguish these two groups either. These results suggest that the
      presence of insulin resistance estimated by SSPG may be a diagnostic marker for
      adrenocortical adenoma in patients with a non-functioning incidentaloma.

PMID- 10915019
TI  - Laparoscopic adrenalectomy for functioning adrenal tumors: clinical experiences
      with 38 cases and comparison with open adrenalectomy.
AB  - We reviewed 38 cases of transperitoneal or retroperitoneal laparoscopic
      adrenalectomy for unilateral benign functioning adrenal tumors and compared the
      results with those of a recent series of 36 patients undergoing an open
      adrenalectomy. The tumors were removed successfully in all but two cases with
      laparoscopy that required open laparotomy. In the other 36 cases of the
      laparoscopy group, mean operative time and blood loss were 225 minutes and 138
      mL, respectively. Mean operative time was significantly longer for the
      laparoscopy group (122 minutes for open surgery: P < 0.0001), whereas mean blood
      loss of the laparoscopy group was almost equal to that of the open surgery group.
      Mean intervals to first ambulation and oral intake, and postoperative hospital
      stay of the laparoscopy group were significantly less than those of the open
      surgery group (1.4 vs 2.0 days: P = 0.014; 1.8 vs 2.9 days: P < 0.0001; and 8.5
      vs 12.9 days: P < 0.0001, respectively). We conclude that laparoscopic
      adrenalectomy is equally effective and less invasive than open adrenalectomy. and
      that it should be considered as the first-choice therapy for benign adrenal
      tumors.

PMID- 10915020
TI  - Laparoscopic adrenalectomy for benign adrenal tumors.
AB  - Laparoscopic adrenalectomy has been rapidly accepted for treatment of benign
      adrenal tumors. To evaluate the advantages of laparoscopic adrenalectomy, we
      examined 55 patients who underwent laparoscopic adrenalectomy. In all patients,
      adrenal tumors were successfully removed. The mean operating time was 143
      minutes, and the estimated mean blood loss was 49 mL in all patients. The
      postoperative course was uneventful in all cases. The mean frequency of
      administration of analgesics was only 2.9 times, and the time elapsed to first
      walking after surgery was 17 hours. The peak white blood cell count and C
      reactive protein values after surgery were 8,266 +/- 1,963/mm3 and 2.5 +/- 1.2
      mg/dL, respectively. Of the 55 patients, 44 underwent total adrenalectomy and
      another 11 underwent partial adrenalectomy, which was introduced in the
      expectation of preserving normal adrenal cortex; it is therefore indicated in
      solitary and peripherally located benign tumors. The mean operating time was 154
      minutes for the total adrenalectomy, which was longer than that of partial
      adrenalectomy (92 minutes). The estimated blood loss was 50 mL for the total and
      46 mL for the partial adrenalectomy. The postoperative course was uneventful and
      surgical outcome was excellent in each group. In conclusion, our results are
      encouraging enough to suggest that laparoscopic adrenalectomy should be a
      preferential therapeutic option for benign adrenal tumors; also, partial
      adrenalectomy could be a safe, effective, and less invasive procedure in selected
      cases.

PMID- 10915021
TI  - Enhanced sensitivity to alkylating agent in lymphocytes from patients with
      multiple endocrine neoplasia type 1.
AB  - Chromosome instability is known to be associated with certain autosomal recessive
      cancer-prone disorders such as Fanconi's anemia. Multiple endocrine neoplasia
      type 1 (MEN 1) is an autosomal dominant disorder characterized by development of
      tumors in two or more endocrine organs, and chromosome instability in patients
      with MEN 1 has been described. The clinical features of MEN 1 are, however,
      distinct from other DNA instability syndromes except predisposition to tumors.
      Therefore, we reevaluated chromosome instability in patients with familial MEN 1.
      An increase in the frequency of chromosome aberrations was observed in MEN 1
      patients but not in control subjects when peripheral mononuclear cells were
      exposed to an alkylating agent, diepoxybutane (DEB). DEB reduced survival of
      mononuclear cells in a dose-dependent manner in both MEN 1 patients and control
      subjects, but this effect was more prominent in MEN I patients. There was no
      apparent correlation between certain MEN1 gene mutations and sensitivity to DEB.
      From these results, we conclude that hypersensitivity to alkylating agents exists
      in patients with MEN 1. Molecular mechanisms of this phenomenon and relationship
      to tumorigenesis in endocrine organs should be elucidated.

PMID- 10915022
TI  - Catecholamine and cytokine response to laparoscopic adrenalectomy in patients
      with pheochromocytoma.
AB  - This study assesses the surgical stress of laparoscopic adrenalectomy (LA) in
      patients with pheochromocytoma using catecholamine and cytokine. The study was
      conducted on one patient who had laparoscopic adrenalectomy performed for
      pheochromocytoma, and three patients as controls who had undergone laparoscopic
      cholecystectomy (LC) for cholecystolithiasis. Catecholamines, tumor necrosis
      factor alpha (TNFalpha) and interleukin 6 (IL-6) were measured at 30-minute
      intervals intraoperatively, and on the first, third and fifth postoperative days
      (POD) respectively. Plasma TNFalpha and IL-6 were measured by a commercially
      available sandwich enzyme-linked immunosorbent assay test. During the operation.
      changes of catecholamine concentration in LA were far larger than those in LC.
      The changes of TNFalpha concentration in LA were also larger than those in LC.
      TNFalpha returned to basal value at the end of the operation in LC, but it did
      not in LA. TNFalpha concentration in LC changed a little after the surgery,
      whereas that in LA sharply increased and was maintained at a high level from 1
      POD until 5 POD. Enhanced cytokine responses were observed in LA compared to LC
      during and after the surgery. We concluded that laparoscopic adrenalectomy may
      give those patients with pheochromocytoma more surgical stress than laparoscopic
      cholecystectomy for cholecystolithiasis, during and after the operation.

PMID- 10915024
TI  - Three patients with adrenal tumors having been treated simply for diabetes
      mellitus.
AB  - Three patients with functional adrenal tumors, Cushing's syndrome, primary
      aldosteronism and pheochromocytoma, who underwent adrenalectomy and were
      subsequently cured, were studied. All these patients had been treated for
      diabetes for several years before the diagnosis of adrenal tumors. In each case
      the state of diabetes before and after surgery, including parameters of insulin
      secretion and insulin resistance, was compared to demonstrate how the adrenal
      disorder influenced the nature of diabetes. In the case of Cushing's syndrome the
      hypercortisolemia caused insulin resistance in the peripheral tissues. In the
      case of primary aldosteronism, excessive production of aldosterone diminished
      insulin secretion possibly through hypokalemia. Pheochromocytoma affected both
      insulin secretion and insulin sensitivity through hypersecretion of
      catecholamines. In all these patients the adrenal tumors were found in clinical
      contexts other than management of diabetes itself. By careful retrospective
      review of these three patients' history, several important points that might have
      drawn the physician's attention to the underlying adrenal disorders were pointed
      out. These included past history of acute myocardial infarction with onset at
      unexpectedly young age in the case of Cushing's syndrome and unexpectedly high
      insulin resistance for the patient's body mass index in the case of
      pheochromocytoma.

PMID- 10915023
TI  - Urinary steroid profile in adrenocortical tumors.
AB  - Determination of the urinary steroid profile has been proposed as a sensitive
      tool for diagnosing adrenocortical tumors. The urinary steroid profiles were
      determined for patients with adrenocortical tumors. Urinary steroids were
      extracted, derivatized to form methyloxime-trimethylsilyl ether and analyzed by
      gas chromatography/mass spectrometry. Patients with adrenal adenomas from primary
      hyperaldosteronism had increased metabolites of 18-hydroxycorticosterone and
      aldosterone, and those with Cushing's syndrome had elevated excretion of 11 
      deoxycortisol, cortisol, 18-hydroxycortisol, and cortisone metabolites. In
      patients with adrenocortical carcinomas, increased levels of metabolites of 11
      deoxycortisol or 33-hydroxy-5-ene steroids were observed. The urinary steroid
      profiles of adrenal adenomas and adrenocortical carcinomas were quite different,
      suggesting the diagnostic validity for discriminating malignant from benign
      diseases.

PMID- 10915025
TI  - Management of adrenal incidentaloma in Japan.

PMID- 10915026
TI  - Laparoscopic adrenalectomy: transperitoneal vs retroperitoneal approaches.
AB  - PURPOSE: To compare the results between transperitoneal and retroperitoneal
      approaches. MATERIALS: Between 17 January 1992 and 31 December 1997, 76 patients
      (31 men and 45 women, 37 right and 37 left, mean 46.7 years old) with adrenal
      tumors including 37 primary aldosteronism. 19 Cushing's syndrome, 15 non
      functioning adrenal tumors, and five pheochromocytomas, underwent laparoscopic
      removal operations in one hospital. Fifty-seven open adrenalectomies were also
      included. METHODS: Fifty-two patients by transperitoneal laparoscopic approach,
      and the other 24 patients by retroperitoneal laparoscopic approach were compared.
      RESULTS: Mean operative time, operative blood loss, time to oral intake, and
      ambulation of transperitoneal approach were 203 min, 115.6 mL, 1.9 days, and 1.4
      days. In patients operated on by the retroperitoneal approach, these factors were
      257 min, 141.6 mL, 1.1 days, and 1.4 days. There was no significant difference in
      any item between the two groups. In patients operated on by open procedure, these
      factors were 143 min, 214 mL, 2.5 days, and 2.4 days. Operating time of the open
      surgery group was significantly shorter than either of the other two groups, and
      all of the other three items of open surgery group were significantly greater
      than either of the other two groups. Open surgery was required in two of 76
      patients treated by endoscopic procedure due to inadvertent injury of the
      anomalous adrenal vein during the transperitoneal approach, and pancreatic injury
      during the retroperitoneal approach. During and after the operation, no
      significant complication was observed. CONCLUSION: Both transperitoneal and
      retroperitoneal laparoscopic adrenalectomies are feasible for adrenal tumors.

PMID- 10915027
TI  - Complications of laparoscopic and retroperitoneoscopic adrenalectomies in 370
      cases in Japan: a multi-institutional study.
AB  - A total of 370 laparoscopic adrenalectomies, including 311 transperitoneal (TP)
      and 59 retroperitoneal (RP) approaches, were performed in nine urologic centers,
      where the laparoscopic adrenalectomy was first begun independently in Japan, and
      their affiliated hospitals between January 1992 and September 1996. The clinical
      diagnoses of those 370 adrenal diseases were primary aldosteronism in 155
      patients, Cushing's syndrome in 61. preclinical Cushing's syndrome in 21.
      pheochromocytoma in 16, nonfunctioning adenoma in 87, complicated cyst in ten,
      myelolipoma in nine, adrenal cancer in four and other diagnoses in eight (table
      1). There was no mortality in this series. Intraoperative complication rate was
      33/370 (9%) in total: 26/311(8%) in the TP procedures and 7/59 (12%) in the RP
      procedures (table 11). Postoperative complication rate was 24/370 (6%) in total:
      22/311 (7%) in the TP procedures and 2/59 (3%) in the RP ones (table 111).
      Conversion rates to open surgery in total, in the TP and in the RP procedures
      were 13/370 (3.5%), 10/311 (3.2%) and 3/59 (5.1 %). respectively (table IV).
      Although the RP procedure has a lower morbidity rate compared to the TP
      procedure, more skill is required to overcome the drawback of the narrow working
      space and fewer anatomical landmarks.

PMID- 10915028
TI  - Laparoscopic adrenalectomy: lateral transabdominal approach vs posterior
      retroperitoneal approach.
AB  - Laparoscopic adrenalectomy has been used to remove a wide variety of adrenal
      neoplasms. Although several laparoscopic approaches to the adrenal gland have
      been described, the lateral transabdominal approach has several advantages when
      compared with other approaches for laparoscopic adrenalectomy. From October 1995
      to July 1999, we performed laparoscopic adrenalectomies on 16 patients, including
      eight posterior retroperitoneal approaches and eight lateral transabdominal
      approaches. Sixteen patients, ranging in age from 23 to 69 years, were treated
      for the following conditions: non-functioning adenoma, four patients;
      aldosteronoma, seven patients; pheochromocytoma, three patients; Cushing's
      adenoma, two patients. The average tumor size was 2.5 +/- 0.5 cm (1.8-3.0 cm,
      median 2.4 cm) in the lateral transabdominal approach, 1.2 +/- 0.8 cm (0.8-3.2
      cm, median 1.75 cm) in the posterior retroperitoneal approach. Average operative
      time of lateral transabdominal approach was significantly shorter than that of
      the posterior retroperitoneal approaches (mean 129 min vs 269 min, P = 0.0005).
      Conversion to laparotomy was required in one patient in the posterior approach.
      Postoperative complication occurred in one pneumothorax in the lateral
      transabdominal approach and two subcutaneous emphysemas in the posterior
      retroperitoneal approach. There was no statistical difference in blood loss
      during the operation in the two groups. There was no mortality in either group.
      The lateral transabdominal approach is a safe and efficient technique for the
      removal of the adrenal neoplasms. Compared with other approaches, this technique
      has a wider working space and also good exposure for removing the adrenal gland.

PMID- 10915029
TI  - Should patients be given an initial low test dose of sildenafil?
AB  - Sildenafil is highly effective for treating erectile dysfunction (ED). However,
      its use has been associated with serious adverse events including myocardial
      infarctions and strokes, and 130 verifiable plus 112 unverified deaths reported
      to the US Food and Drug Administration during the 8 months after sildenafil was
      introduced in the US, and 522 reported deaths during the 13.5 months after its
      introduction. Moreover, some events have occurred in men taking their first dose
      of the agent, suggesting that sildenafil, like some drugs that affect blood
      pressure, may provoke a first-dose reaction. This possibility warrants extra
      caution to be used when initiating treatment with sildenafil. Such caution is not
      currently provided by the current dosage guidelines that, for example, recommend
      the use of sildenafil 50 mg initially for most men between the ages of 18 and 65
      years, despite wide differences in bodyweight, age, drug metabolism, health
      status and usage of other medications. It can be difficult to identify the
      patient who may be unusually sensitive to the effects of sildenafil. Exercise
      stress tests have been recommended, but serious adverse events have occurred in
      men with normal stress tests following the ingestion of sildenafil. Blood
      pressure monitoring following sildenafil administration will not prevent a
      serious adverse drug event already in progress. This article discusses the
      advantages and disadvantages of initiating treatment with a low test dose of
      sildenafil, performed at home or in the doctor's office. The advantages of this
      approach include: (i) identifying patients who are highly sensitive to the
      effects of sildenafil and who may need no higher dose; (ii) minimising adverse
      effects such as flushing and dizziness that often frighten patients and may
      affect adherence; (iii) avoidance of major adverse events; and (iv) reassuring
      patients with ED who remain wary about trying sildenafil therapy.

PMID- 10915030
TI  - Safety of inhaled and intranasal corticosteroids: lessons for the new millennium.
AB  - Although inhaled and intranasal corticosteroids are first-line therapy for asthma
      and allergic rhinitis, there has recently been an increasing awareness of their
      propensity to produce systemic adverse effects. The availability of more potent
      and lipophilic corticosteroids and new chlorofluorocarbon (CFC)-free formulations
      has focused attention on these safety issues. The main determinant of systemic
      bioavailability of these drugs is direct absorption from the lung or nose, where
      there is no first-pass inactivation. Consequently, the systemic bioavailability
      of inhaled corticosteroids is greatly influenced by the efficiency of the inhaler
      device. Thus, when comparing different inhaled corticosteroids it is imperative
      to consider the unique drug/device interaction. The pharmacokinetic profile is
      important in determining the systemic bioactivity of inhaled and intranasal
      corticosteroids. For highly lipophilic drugs, such as fluticasone propionate or
      mometasone furoate, there is preferential partitioning into the systemic tissue
      compartment, and consequently a large volume of distribution at steady state. In
      contrast, drugs with lower lipophilicity, such as triamcinolone acetonide or
      budesonide, have a smaller volume of distribution. The systemic tissue
      compartment may act as a slow release reservoir, resulting in a long elimination
      half-life for the lipophilic drugs. For intranasal corticosteroids, a high degree
      of lipophilicity diminishes water solubility in mucosa and therefore increases
      the amount of drug swept away by mucociliary clearance before it can gain access
      to tissue receptor sites. This may reduce the anti-inflammatory efficacy in the
      nose, but might also reduce the propensity for direct systemic absorption from
      the nasal cavity. The hydrofluoroalkane (HFA) formulations of beclomethasone
      dipropionate are solutions and exhibit a much higher respirable fine particle
      dose than do the CFC formulations. Dose-response studies with one of the HFA
      formulations have shown therapeutic equivalence at half the dosage, with little
      evidence of adrenal suppression at dosages up to 800 microg/day. A lack of
      similar studies for another of the available HFA formulations has led to a
      discrepancy in the recommendations for equivalence. Although in vitro studies
      have pointed to a similar fine particle distribution for the HFA and CFC
      formulations of fluticasone propionate, this is not supported by in vivo data for
      lung bioavailability, suggesting that care will be required when switching these
      formulations. Prescribers of inhaled and intranasal corticosteroids should be
      aware of the potential for long term systemic effects. The safest way to use
      these drugs is to 'step-down' to achieve the lowest possible effective
      maintenance dosage.

PMID- 10915033
TI  - Use of antifungal drugs in pregnancy: a focus on safety.
AB  - The use of antifungals in pregnancy requires special consideration for the safety
      of the developing fetus. Clinicians now have an increased repertoire of both
      topical and systemic antimycotics available to treat superficial or mucotaneous
      fungal infections including Candida vaginitis. The ability of many nontopical
      antifungals to penetrate the placenta and achieve measurable, often therapeutic,
      concentrations in cord blood, fetal tissue and amniotic fluid means that evidence
      exists of successful treatment of all varieties of systemic fungal disease in
      pregnant women, even with placental involvement. However, for the same reasons,
      safety considerations remain a concern. Although the use of azoles as topical
      agents for superficial infections is both efficacious and well tolerated,
      especially when used for short periods, systemic azole therapy is not recommended
      in pregnancy. Accordingly, amphotericin B remains the drug of choice for
      systemic, invasive mycotic infections, whether life-threatening or less severe.
      Unfortunately little if any information is available regarding the safety of the
      newer lipid formulations of amphotericin B. There is a general reluctance to
      perform randomised, comparative studies involving antifungal agents in pregnancy,
      hence cumulative anecdotal reports form much of the available data; animal
      studies, although useful, have several drawbacks. There is a need for additional
      safe and effective new antifungal agents for widespread use in pregnant women.

PMID- 10915034
TI  - Reporting of adverse drug reactions by poison control centres in the US.
AB  - BACKGROUND: Although US poison control centres manage approximately 30,000
      adverse drug reactions each year, the extent of voluntary reporting of these
      events to the US Food and Drug Administration (FDA) MedWatch spontaneous
      surveillance programme is unknown. METHODS: A survey was mailed to directors of
      all 72 US poison control centres during April 1999 to determine their practices
      and opinions on reporting adverse drug reactions. The survey requested
      information on the poison control centre staff's practices in reporting adverse
      drug reactions to the FDA MedWatch programme during 1998. RESULTS: A total of 56
      fully completed surveys were returned. Of the respondents, 30 had not directly
      submitted adverse drug reaction reports to the FDA, 22 had submitted 10 or less,
      and 4 had submitted a total of 47 during 1998. Reasons given for not routinely
      reporting adverse drug reactions included adverse drug reactions reporting is not
      part of the regular routine (20%), lack of time to complete forms (15%),
      inability to determine causality (13%), most reactions are already reported and
      not unique (10%), reporting to the FDA is too much work (9%), and responsibility
      rests with the attending physician (7%). Direct reporting to MedWatch of any
      cases of adverse drug reactions was more likely when the poison control centre
      was certified by the American Association of Poison Control Centers (p < 0.05;
      odds ratio = 5.1; 95% confidence interval 1.1 to 23.5); however, this practice
      was not associated with documenting deaths associated with adverse drug
      reactions, having more than 75% of the staff of the Poison Information
      Specialists composed of pharmacists or nurses, or managing greater than 20,000 or
      34,000 human exposure cases during 1998. Approximately half of the poison control
      centres directly or indirectly reported some adverse drug reactions to the FDA by
      virtue of contacting the manufacturer or cooperating with postmarketing
      surveillance. CONCLUSION: Poison control centres represent an underutilised
      source of reporting to MedWatch, but several internal and external obstacles
      limit the direct reporting of adverse drug reactions routinely.

PMID- 10915035
TI  - Cell adhesion antagonists: synthesis and evaluation of a novel series of
      phenylalanine based inhibitors.
AB  - Several phenylalanine based inhibitors were synthesized as antagonists of the
      leukocyte cell adhesion process that is mediated through the interactions of the
      mucosal addressin cell adhesion molecule (MAdCAM) and the integrin alpha4beta7.
      Analogues 20, 21, 22 and 24 displayed inhibition of adhesion in a cell based
      assay in the low micromolar range.

PMID- 10915036
TI  - Solid phase synthesis of [18F]labelled peptides for positron emission tomography.
AB  - A strategy for the solid phase synthesis of [18F]labelled peptides has been
      developed. The peptides were prepared on solid support and acylated with 4
      [18F]fluorobenzoic acid using HATU within 3 min and the labelled peptide was
      released from the solid support within 7 min. The [18F]labelled peptides were
      produced in good purity with a specific activity of 20-25 GBq/micromol.

PMID- 10915031
TI  - Adverse reactions to new anticonvulsant drugs.
AB  - A lack of systematic pharmacoepidemiological studies investigating adverse drug
      reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the
      incidence of anticonvulsant-related ADRs. Most of the available information in
      this regard stems from clinical trial experience, case reports and postmarketing
      surveillance, sources that are not, by any means, structured to provide precise
      data on adverse event epidemiology. For various ethical, statistical and
      logistical reasons, the organisation of structured clinical trials that are
      likely to provide substantial data on ADRs is extremely difficult. This review
      concentrates on current literature concerning serious and life-threatening ADRs.
      As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants
      are CNS-related, although there are several that are apparently unique to some of
      these new drugs. Gabapentin has been reported to cause aggravation of seizures,
      movement disorders and psychiatric disturbances. Felbamate should only be
      prescribed under close medical supervision because of aplastic anaemia and
      hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from
      simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and
      deterioration of seizure control have also been reported with lamotrigine
      treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine.
      Hyponatraemia associated with oxcarbazepine is also a problem; however, it is
      less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus
      has been reported frequently with tiagabine, although there are insufficient data
      at present to identify risk factors for this ADR. Topiramate frequently causes
      cognitive ADRs and, in addition, also appears to cause word-finding difficulties,
      renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure
      aggravation, especially in myoclonic seizures. There have been rare reports of
      other neurological ADRs to vigabatrin, such as encephalopathy, aphasia and motor
      disturbances. Vigabatrin-induced visual field constriction is the latest and most
      worrying ADR. Many questions regarding the nature of this potentially serious ADR
      remain unanswered, as no prospective controlled study examining the phenomenon
      has been published. Rare cases of behavioural ADRs and IgA and IgG2 deficiency
      associated with the use of zonisamide have been reported. However, relatively few
      patients so far have been exposed to this drug, and therefore more postmarketing
      information is required. The relatively late establishment of aplastic anaemia
      and hepatic failure as potentially fatal ADRs of felbamate, and of visual field
      constriction with vigabatrin, should serve as ample reminders that ADRs can
      appear at any time.

PMID- 10915032
TI  - Lipodystrophy syndrome in HIV infection: what is it, what causes it and how can
      it be managed?
AB  - Since the introduction of HIV-1 protease inhibitors as components of
      antiretroviral drug combination regimens, the clinical course of HIV disease and
      opportunistic infections has changed dramatically. Besides the favourable
      virological, immunological and clinical impact of highly active antiretroviral
      therapy (HAART), several adverse drug reactions have been observed in patients
      with HIV receiving therapy. Particularly, peripheral lipodystrophy, central
      adiposity, dyslipidaemia and insulin resistance have been described with a
      prevalence of up to 80% in patients infected with HIV, and attributed to almost
      all components of HAART. Hyperlipidaemia is characterised by an increase of low
      and very low density lipoprotein-cholesterol as well as apolipoproteins B and E.
      Several studies strongly suggest that there are either multiple syndromes or a
      variety of factors inducing different changes that influence the ultimate
      phenotype. Similarities between HIV-associated fat redistribution and metabolic
      abnormalities with both inherited lipodystrophies and benign symmetric
      lipomatosis suggest the pathophysiological involvement of, for example, nuclear
      factors like lamin A/C and drug-induced mitochondrial dysfunction. Moreover,
      there is some evidence that cytokines and hormones impair fat and glucose
      homeostasis in patients with HIV receiving HAART. Three years after the first
      description of HIV therapy-associated abnormal fat redistribution, there is still
      an ongoing discussion about the case definition, diagnostic procedure and
      treatment options for both body shape changes and metabolic disturbances.
      Regarding therapy, there is a major concern about possible complex
      pharmacological interactions and overlapping adverse effects between HAART and,
      for example, lipid-lowering therapy. In addition, the likely contribution of both
      nucleoside analogue reverse transcriptase inhibitors and protease inhibitors to
      the development of abnormal fat redistribution in patients with HIV limits
      options of changing to alternative effective antiretroviral drug combinations.
      Thus, the occurrence of hyperlipidaemia, maturity onset diabetes mellitus, and
      marked changes in body habitus resulted in important social and clinical
      consequences such as an increased risk of atherosclerosis. It also sheds new
      light on the use of protease inhibitors regarding risk factors for the initial
      treatment decision. In this article, we discuss the features, pathogenesis and
      treatment options for body fat redistribution and metabolic disturbances
      associated with HAART in HIV-1 infection.

PMID- 10915037
TI  - A concise synthesis of the 6-O- and 6'-O-sulfated analogues of the sialyl Lewis X
      tetrasaccharide.
AB  - The octyl glycoside of the sialyl Lewis X tetrasaccharide and its 6-O-sulfated
      and 6'-O-sulfated analogues were chemically synthesized in a concise manner
      starting from readily accessible monosaccharide intermediates. The synthesis
      involved formation of an orthogonally protected tetrasaccharide intermediate from
      which all three materials were prepared. A selective catalytic hydrogenolysis of
      four O-benzyl ethers in presence of a 4,6-O-benzylidene group was the key step in
      the synthetic scheme.

PMID- 10915038
TI  - Mechanistic studies on prolyl-4-hydroxylase: the vitamin C requiring uncoupled
      oxidation.
AB  - A deuterated substrate for the human type I prolyl-4-hydroxylase was synthesized
      and its V/K deuterium isotope effect was determined to be 3.4 +/- 0.2. This
      isotope effect was attributed to the uncoupled oxidation. A dehydroproline
      containing tetrapeptide was also found to stimulate the uncoupled oxidation.

PMID- 10915040
TI  - Synthesis and in vitro evaluation of human FP-receptor selective prostaglandin
      analogues.
AB  - The in vitro evaluation of a series of saturated prostaglandins revealed that
      compounds with omega chain aromatic rings retain nanomolar potency for the human
      prostaglandin F receptor (hFP receptor), exemplified by compound 8. In contrast,
      the double bonds are required for activity in the series with an acyclic omega
      chain as in PGF2alpha.

PMID- 10915039
TI  - New ratiometric fluorescent calcium indicators with moderately attenuated binding
      affinities.
AB  - Mono-halogenated derivatives of the calcium indicators fura-2 and indo-1 were
      synthesized and their spectroscopic properties evaluated. Halogenation ortho or
      para to the bridging oxygen in the BAPTA nucleus had a more pronounced weakening
      effect on binding affinity than in the meta position in the fura derivatives. Two
      new excitation ratioable fluorescent calcium indicators, benzothiaza-1 and 2,
      were also synthesized. Kd values of 400 nM to 5.3 microM [Ca2+] were observed in
      these families of new probes.

PMID- 10915041
TI  - Synthesis of fluorescent probes directed to the active site gorge of
      acetylcholinesterase.
AB  - Six organophosphorus compounds linked to fluorophore groups were prepared in an
      effort to selectively modify the active site of acetylcholinesterase and deliver
      probes to the gorge region. Two compounds that vary by the length of a methylene
      (CH2) group, pyrene-SO2NH(CH2)nNHC(O)CH2CH2P(O)(OEt)(F) (where n = 2 or 3) were
      found to be potent, irreversible inhibitors of recombinant mouse AChE (Ki
      approximately 10(5) M(-1) min(-1)). Size exclusion chromatography afforded a
      fluorescently-labeled cholinesterase conjugate.

PMID- 10915042
TI  - Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV
      protease inhibitor library.
AB  - An efficient combination solution-phase/solid-phase route enabling the
      diversification of the P1', P2', and P3 subsites of indinavir has been
      established. The synthetic sequence can facilitate the rapid generation of HIV
      protease inhibitors possessing more favorable pharmacokinetic properties as well
      as enhanced potencies. Multiple compound dosing in vivo may also accelerate the
      identification of potential drug candidates.

PMID- 10915043
TI  - Substituted oxazole benzenesulfonamides as potent human beta3 adrenergic receptor
      agonists.
AB  - As a part of our investigation into the development of orally bioavailable beta3
      adrenergic receptor agonists, we have identified a series of substituted oxazole
      derivatives that are potent beta3 agonists with excellent selectivity against
      other beta receptors. Several of these compounds showed excellent oral
      bioavailability in dogs. One example, cyclopentylethyloxazole 5f is a potent
      beta3 agonist (EC50 = 14 nM, 84% activation) with 340-fold and 160-fold
      selectivity over beta1 and beta2 receptors, respectively, and has 38% oral
      bioavailability in dogs.

PMID- 10915044
TI  - Synthesis and PTP1B inhibition of novel 4-aryl-1-oxa-9
      thiacyclopenta[b]fluorenes.
AB  - Novel 4-aryl-1-oxa-9-thiacyclopenta[b]fluorenes were designed, synthesized, and
      evaluated as inhibitors of the protein tyrosine phosphatase, PTP1B. Compounds 3
      (IC50 = 284 nM) and 4 (IC50 = 74 nM), showed nanomolar potency against PTP1B
      (TRDI(P)YETD(P)Y(P)YRK as substrate). Compound 4 also lowered insulin in the
      diabetic ob/ob mouse at a dose of 10 mg/kg/day, p.o.

PMID- 10915045
TI  - Efficient synthesis of rhodamine conjugates through the 2'-position.
AB  - Reaction of substrates containing primary amines with rhodamine 2'-esters cleanly
      produces fluorescent rhodamine 2'-amide conjugates at ambient temperature. Only
      primary amines react with the esters under these conditions. Chemoselectivity can
      thus be achieved in substrates containing different types of amines.

PMID- 10915046
TI  - Parallel synthesis and evaluation of N-(1-phenylethyl)-5-phenyl-imidazole-2
      amines as Na+/K+ ATPase inhibitors.
AB  - A series of N-(1-phenylethyl)-5-phenyl-imidazole-2-amines was prepared using
      solution-phase, parallel synthesis and evaluated for Na+/K+ ATPase inhibition.

PMID- 10915048
TI  - Synthesis of thiophenyl substituted cyclohexa-2,4-dien-1-one and its
      photocleavage coupling reaction with amines.
AB  - Thiophenyl substituted cyclohexa-2,4-dien-1-ones were synthesized and photolyzed
      in the presence of various amines to afford the amides containing diene moeties
      via the ketene intermediate under visible light irradiation at 38 degrees C.

PMID- 10915047
TI  - Formation of multilamellar vesicles ('onions') in peptide based surfactant.
AB  - Concentration dependent morphological characteristics of a novel dipeptide
      derivative Lys-Asp-Lauryl.HBr (1) has been presented. Evidence for "onion" like
      vesicle formation at higher concentration (>8.2 x 10(-3) M) of peptide (1) in
      aqueous medium was obtained from conductance and 90 degrees light scattering
      measurements, and cryo-transmission electron microscopic studies.

PMID- 10915049
TI  - 1-Aminomethylisoquinoline-4-carboxylates as novel dipeptidylpeptidase IV
      inhibitors.
AB  - Structure-activity relationship within a series of 1-aminoalkylisoquinoline-4
      carboxylates as inhibitors of DPP-IV is described. A primary aminomethyl group is
      required to maintain biological activity. Substitution of the isoquinoline at the
      6- and 8-positions with methoxy groups increases potency to 53 times that of the
      lead compound SDZ 029-576.

PMID- 10915050
TI  - Syntheses and binding affinities of 6-nitroquipazine analogues for serotonin
      transporter. Part 1.
AB  - 6-Nitroquipazine has been known as one of the most potent and selective
      inhibitors of serotonin transporter in vitro and in vivo. Nine derivatives of 6
      nitroquipazine were synthesized and tested for their potential abilities to
      displace [3H]citalopram binding to the rat cortical membranes.

PMID- 10915052
TI  - The design and synthesis of thrombin inhibitors: the introduction of in vivo
      efficacy and oral bioavailability into benzthiazolylalanine inhibitors.
AB  - The further optimisation of the novel lead compound CGH752 (Fig. 1) is described.
      By introducing various substituents into the 6-position of the 3,3
      dimethyltetrahydroquinoline (DMTHQS) ring we have been able to favourably affect
      the in vitro and in vivo activity, and the pharmacokinetics of such compounds.
      One of the inhibitors synthesised (CGH1484) is bioavailable and shows efficacy in
      animal models of thrombosis.

PMID- 10915051
TI  - The design and synthesis of thrombin inhibitors: analogues of MD805 containing
      non-polar surrogates for arginine at the P1 position.
AB  - A series of monocyclic and bicyclic amino acids have been synthesised and
      incorporated into thrombin inhibitors based on CGH728, an analogue of the
      Mitsubishi compound MD805. Benzthiazolylalanine (Bta) was found to be a good non
      polar substitute for arginine at the P1 position, yielding compounds with low
      nanomolar potency and good selectivity for thrombin.

PMID- 10915053
TI  - Synthesis and biological activity of 4'-methoxy derivatives of abscisic acid.
AB  - Replacing the 4'-carbonyl group of abscisic acid with a methoxy group does not
      affect the abscisic acid (ABA)-like activities of the product in barley aleurone
      protoplasts, although the reduction of ABA to 4'-hydroxyl derivatives
      significantly reduces the ABA-like activity of the products. This suggests that
      methoxy derivatives of abscisic acid might be used to produce probes for ABA
      binding proteins.

PMID- 10915054
TI  - Kinetic characterisation of ene-diol-based inhibitors of alpha-amylase.
AB  - A kinetic analysis of the inhibition of malt alpha-amylase by compounds based on
      ascorbic acid has shown the mode of inhibition to be competitive for the parent
      compound, but more complex for its derivatives. We have further simplified the
      ascorbic acid ene-diol pharmacophore by demonstrating that dihydroxyfumaric acid
      is also a good inhibitor of malt alpha-amylase.

PMID- 10915055
TI  - Solid phase synthesis of aminoboronic acids: potent inhibitors of the hepatitis C
      virus NS3 proteinase.
AB  - Use of a resin bound diol as a boronic acid protecting group has been developed
      to allow the parallel synthesis of potent inhibitors of the hepatitis C virus NS3
      serine proteinase.

PMID- 10915056
TI  - Difluoroketones as inhibitors of matrix metalloprotease-13.
AB  - Substrate-like difluoroketones have been prepared as potential inhibitors of MMP
      13. Weak inhibition was seen with the key target 2. This and the more potent
      activity of intermediate 7b illustrates that hydrated ketones can be used to
      inhibit MMP-13 and perhaps other members of this class of enzymes.

PMID- 10915057
TI  - 4-Amino-1,2-dithiolane-4-carboxylic acid (Adt) as cysteine conformationally
      restricted analogue. Synthetic protocol for Adt containing peptides.
AB  - An efficient and versatile protocol to incorporate the achiral and C(alpha,alpha)
      tetrasubstituted 4-amino-1,2-dithiolane-4-carboxylic acid Adt (1) residue into
      peptides is described. The 2,2-bis[(benzylthio)methyl]glycine N-carboxy anhydride
      (5) was found to be the key reactive intermediate from which both Boc-Adt-OMe (8)
      and the glutathione analogue H-Glu(-Adt-Gly-OH)-OH (12) can be obtained.

PMID- 10915058
TI  - Synthesis and antifungal activities of 5/6-arylamino-4,7-dioxobenzothiazoles.
AB  - 5/6-Arylamino-4,7-dioxobenzothiazoles were synthesized and tested for in vitro
      antifungal activities against pathogenic fungi. Most of the tested 4,7
      dioxobenzothiazoles exhibited potent antifungal activities against Candida
      species and Aspergillus niger.

PMID- 10915059
TI  - Enhanced binding of aminoglycoside dimers to a "dimerized" A-site 16S rRNA
      construct.
AB  - In this work, we investigated the binding of a series of dimeric aminoglycoside
      molecules to (i) a 27 nt A-site 16S rRNA construct, and (ii) an artificially
      grafted 46 nt 'dimerized' A-site 16S rRNA construct. It was observed that the
      dissociation constants of dimeric aminoglycosides to the dimerized A-site 16S
      rRNA construct can achieve up to approximately 19-fold enhancement compared to
      the monomeric aminoglycoside molecules.

PMID- 10915060
TI  - Structure-activity relationships of neuropeptide Y Y1 receptor antagonists
      related to BIBP 3226.
AB  - Analogues of BIBP 3226, (R)-N(alpha)-diphenylacetyl-N-(4
      hydroxybenzyl)argininamide, were synthesized and investigated for Y1 antagonism
      (Ca2+-assay, HEL cells) and binding on Y1, Y2 and Y5 receptors. Replacing the
      benzylamino by a tetrahydrobenzazepinyl group preserves most of the Y1 activity.
      Combination with a N(G)-phenylpropyl arginine and a N(alpha)-p-biphenylylacetyl
      moiety shifted the NPY receptor selectivity towards Y5.

PMID- 10915061
TI  - Acid catalyzed Michael additions to artemisitene.
AB  - A series of 14-substituted-artemisinin and 9-epiartemisinin derivatives was
      prepared by a titanium-tetrachloride catalyzed addition of trimethylsilyl enol
      ethers to artemisitene. Several compounds were four to seven times more active
      than artemisinin against Plasmodium falciparum.

PMID- 10915062
TI  - Michael adducts of ascorbic acid as inhibitors of protein phosphatase 2A and
      inducers of apoptosis.
AB  - Michael adducts of ascorbic acid with alpha,beta-unsaturated carbonyl compounds
      have been shown to be potent inhibitors of protein phosphatase 1 (PP1) without
      affecting cell viability at the respective concentrations. Here we were able to
      show that higher concentrations can partially inhibit PP2A activity and
      concomitantly induce apoptotic cell death. A nitrostyrene adduct of ascorbic acid
      proved to be a more potent and effective inhibitor of PP2A as well as a stronger
      inducer of apoptosis. These adducts only slightly lost their cytotoxic potential
      in multidrug resistant cells that were 10-fold less sensitive to apoptosis
      induction by okadaic acid and vinblastine.

PMID- 10915063
TI  - The synthesis and in vitro cytotoxic studies of novel bis-naphthalimidopropyl
      polyamine derivatives.
AB  - Bis-naphthalimidopropyl putrescine (BNIPPut), spermidine (BNIPSpd), spermine
      (BNIPSpm) and oxa-putrescine (BNIPOPut) were synthesised and their growth
      inhibitory properties characterised. All these compounds except for BNIPOPut,
      showed high in vitro cytotoxic activity (with mean GI50 values between 0.5 and
      8.45 microM) and selectivity against cancer cells derived from nine different
      human tumours. The increased content of nitrogen atoms in the linker chain of
      BNIPSpd and BNIPSpm significantly improved their aqueous dissolution properties
      with a marginal decrease in their cytotoxic activity.

PMID- 10915064
TI  - Binding interactions of vancomycin tracers with a bacterial cell wall
      peptidoglycan analogue.
AB  - Binding interactions between several vancomycin tracers and (N,N'-diacetyl)KDADA
      in solution were evaluated in a competition format using a surface plasmon
      resonance instrument. Tracers derivatized from the carboxy terminus or the N
      vancosaminyl sugar moiety of vancomycin bind the peptide with an affinity similar
      to that of underivatized vancomycin. In contrast, N-methylleucyl derivatized
      vancomycin tracers bind the peptide with a reduced affinity relative to
      vancomycin.

PMID- 10915065
TI  - Biomimetic ligands for transition metals: catechol-containing peptides.
AB  - The tetrapeptide ligands 6a and 6b containing a catechol moiety have been
      synthesised and their metal binding with Fe(III), Mn(III) and Cu(II) has been
      studied using fluorescence spectroscopy.

PMID- 10915066
TI  - Varicella mortality: trends before vaccine licensure in the United States, 1970
      1994.
AB  - We examined varicella deaths in the United States during the 25 years before
      vaccine licensure and identified 2262 people who died with varicella as the
      underlying cause of death. From 1970 to 1994, varicella mortality declined,
      followed by an increase. Mortality rates were highest among children; however,
      adult varicella deaths more than doubled in number, proportion, and rate per
      million population. Despite declining fatality rates, in 1990-1994, adults had a
      risk 25 times greater and infants had a risk 4 times greater of dying from
      varicella than did children 1-4 years old, and most people who died of varicella
      were previously healthy. Varicella deaths are now preventable by vaccine.
      Investigation and reporting of all varicella deaths in the United States is
      needed to accurately document deaths due to varicella, to improve prevention
      efforts, and to evaluate the vaccine's impact on mortality.

PMID- 10915067
TI  - The senescence-accelerated mouse shows aging-related defects in cellular but not
      humoral immunity against influenza virus infection.
AB  - The senescence-accelerated mouse (SAM) strain P1, which has a short life span,
      was adopted as a murine model for an investigation of the pathogenesis of viral
      infection in elderly adults. After intranasal inoculation with influenza A virus,
      the SAM-P1 mice showed a higher rate of mortality, with prolonged virus growth in
      the lungs. The increased susceptibility was associated with impaired activity of
      both NK cells and virus-specific cytotoxic T lymphocytes. The production of
      interferon-gamma and interleukin-12 was significantly restrained, which suggests
      a partial deficiency of the T helper (Th) 1 cells. In contrast, the immunologic
      activity of the Th2 cells appeared to be functionally normal, judging from the
      release of large amounts of interleukin-4 followed by production of appropriate
      amounts of influenza virus-specific antibody. It is suggested that the
      elicitation of cellular immunity is an important and effective procedure for
      protecting the elderly from influenza virus infection.

PMID- 10915068
TI  - The protein kinase-interacting domain in the hepatitis C virus envelope
      glycoprotein-2 gene is highly conserved in genotype 1-infected patients treated
      with interferon.
AB  - The hepatitis C virus (HCV) envelope glycoprotein-2 inhibits the interferon (IFN)
      induced, double-stranded RNA-activated protein kinase (PKR) via the PKR
      eukaryotic initiation factor-2alpha phosphorylation homology domain (PePHD). The
      present study examined the genetic variability of the PePHD in patients receiving
      IFN therapy. The PePHD from 12 HCV genotype 1 (HCV-1)-infected patients receiving
      daily IFN therapy was amplified by reverse-transcriptase polymerase chain
      reaction and analyzed by direct and clonal sequencing. The PePHD was highly
      conserved in 38 HCV GenBank isolates. There was no difference in pretreatment
      PePHD sequences isolated from IFN responders versus nonresponders. The major
      PePHD quasi-species variant did not change after 6 weeks of daily IFN therapy,
      and in 1 patient the major quasi-species variant did not change during 9 months
      of observation. Sequencing of 25 pretreatment PePHD clones from 3 patients
      confirmed that there was extremely low sequence variability surrounding the
      PePHD. The PePHD is highly conserved in HCV-1-infected IFN responders and
      nonresponders and does not appear to evolve in response to IFN therapy.

PMID- 10915069
TI  - Detection of a major gene predisposing to human T lymphotropic virus type I
      infection in children among an endemic population of African origin.
AB  - Human T lymphotropic virus type I (HTLV-I) is a human oncoretrovirus that causes
      an adult T cell leukemia/lymphoma and a chronic neuromyelopathy. To investigate
      whether familial aggregation of HTLV-I infection (as determined by specific
      seropositive status) could be explained in part by genetic factors, we conducted
      a large genetic epidemiological survey in an HTLV-I-endemic population of African
      origin from French Guiana. All of the families in 2 villages were included,
      representing 83 pedigrees with 1638 subjects, of whom 165 (10.1%) were HTLV-I
      seropositive. The results of segregation analysis are consistent with the
      presence of a dominant major gene predisposing to HTLV-I infection, in addition
      to the expected familial correlations (mother-offspring, spouse-spouse) due to
      the virus transmission routes. Under this genetic model, approximately 1. 5% of
      the population is predicted to be highly predisposed to HTLV-I infection, and
      almost all seropositive children <10 years of age are genetic cases, whereas most
      HTLV-I seropositive adults are sporadic cases.

PMID- 10915070
TI  - The CCR5Delta32 allele slows disease progression of human immunodeficiency virus
      1-infected children receiving antiretroviral treatment.
AB  - The role of the CCR5Delta32 allele in human immunodeficiency virus (HIV)-1
      related disease progression was analyzed for 457 antiretroviral-naive children
      who had participated in the Pediatric AIDS Clinical Trials Group 152 study, which
      demonstrated that didanosine (ddI) or zidovudine + ddI treatments were superior
      to zidovudine alone. The CCR5Delta32 allele was detected at an overall frequency
      of 6.1% (28/457). At study entry, heterozygote children (wild type [wt]/Delta32)
      had higher baseline median CD4(+) counts/mm(3) than wt/wt children had (1035 vs.
      835 cells/mm(3); P=. 043), higher mean weight-for-age Z scores (-0.15 vs. -0.84;
      P=.01), and a trend toward less cortical atrophy (P=.059). During antiretroviral
      treatment and study follow-up, there was a trend toward less disease progression
      and death among heterozygote children than among wt/wt children (P=.056; relative
      hazard, 0.28; 95% confidence interval, 0.07-1.13) independent of the
      antiretroviral treatment to which they were randomized.

PMID- 10915071
TI  - Correlation between human immunodeficiency virus genotypic resistance and
      virologic response in patients receiving nelfinavir monotherapy or nelfinavir
      with lamivudine and zidovudine.
AB  - The relationship between detectable human immunodeficiency virus (HIV) genotypic
      resistance and virologic response was compared in patients receiving nelfinavir
      as monotherapy (16 weeks) or in combination with lamuvidine and zidovudine (48
      weeks). Two patient groups were defined on the basis of the presence or absence
      of substitutions associated with nelfinavir, a protease (PR) inhibitor, and/or a
      reverse transcriptase (RT) inhibitor. HIV RNA levels <50 copies/mL were achieved
      in 17 (85%) of 20 combination-therapy patients without genotypic resistance (PR
      RT(-)) versus only 1 (17%) of 6 patients with genotypic resistance (PR-RT(+)). PR
      RT(-) patients exhibited greater and more durable virus suppression compared with
      PR-RT(+) patients. All 6 PR-RT(+) patients had virus with M184V (lamuvidine
      resistance); 3 isolates also contained D30N (nelfinavir resistance). M184V
      preceded D30N in all determinable instances. In this study, suppression of HIV
      replication to <50 copies/mL was associated with durable response and reduced
      incidence of resistance. Results also indicate that combination regimens can fail
      despite the absence of detectable genotypic PR resistance.

PMID- 10915073
TI  - Evaluation of CD4+ T cell function In vivo in HIV-infected patients as measured
      by bacteriophage phiX174 immunization.
AB  - Bacteriophage phiX174 immunization was used to measure CD4(+) T cell function in
      vivo in human immunodeficiency virus (HIV)-infected patients across all disease
      stages. Function was evaluated by measuring the ability of T cells to provide
      help to B cells in antibody production, amplification, and isotype switching. A
      total of 33 patients and 10 controls received 3 bacteriophage phiX174
      immunizations 6 weeks apart. The patients' responses regarding bacteriophage
      specific total antibody titers and IgG titers were quantitatively and
      qualitatively inferior to the controls' responses. Overall, 7 of 33 patients had
      normal T cell function. Baseline CD4 counts provided the strongest correlation
      with total antibody and IgG titers. HIV RNA had a weaker association with
      responses but had some predictive power among patients with a CD4 count >200
      cells/microL. Bacteriophage phiX174 immunization seems to be a useful tool for
      measuring immune function in vivo, which suggests that most HIV-infected patients
      may have abnormal CD4(+) T cell function despite adequate antiretroviral
      treatment.

PMID- 10915072
TI  - Pooled analysis of 3 randomized, controlled trials of interleukin-2 therapy in
      adult human immunodeficiency virus type 1 disease.
AB  - We collected human immunodeficiency virus (HIV) disease progression, survival,
      most recent CD4 cell count, and plasma HIV RNA levels from patients (n=157) who
      participated in randomized clinical trials of interleukin (IL)-2 that commenced
      before 1995. Data were available for 155 (99%) patients. Statistical analyses
      were based on the intention-to-treat principle. Median follow-up was 28 months
      and 30 months for control and IL-2 patients, respectively. Twenty-five (16%)
      patients developed AIDS or died during follow-up (16 control patients vs. 9 IL-2
      patients; R2=0.57; P=.22). Mean change from baseline CD4 cell count was
      significantly higher in patients randomized to receive IL-2 (368 vs. 153
      cells/microL; P=.003). Mean change from baseline plasma HIV RNA was significantly
      lower in patients randomized to receive IL-2 (-0.98 vs. -0.63 log copies/mL;
      P=.004). Significant improvements in CD4 cell count and plasma HIV RNA in
      recipients of IL-2 relative to control patients were associated with a
      nonsignificant trend toward improved clinical outcome.

PMID- 10915074
TI  - Human immunodeficiency virus type 1 subtype E envelope recombinant peptides
      containing naturally immunogenic epitopes.
AB  - A series of recombinant peptides of the human immunodeficiency virus type 1 (HIV
      1) subtype E envelope were used to address the question of whether immunogenic
      epitopes similar to those described for the subtype B envelope are also present
      in structurally analogous regions of another HIV-1 subtype with divergent
      sequences. Five recombinant peptides, covering the V2 and V3 domains of gp120,
      the cysteine-loop region of gp41, a gp41 region involved in oligomerization, and
      the cytoplasmic tail of gp41, were found to react with >50% of the serum samples
      analyzed. All but the V2 region in the HIV-1 subtype B envelope have been
      reported to contain continuous epitopes that are highly immunogenic during
      natural infection. This finding suggests that, despite the sequence divergence
      between subtype E and B envelopes, most of the continuous epitopes that are
      highly immunogenic during natural infection are located at structurally analogous
      regions of the envelope.

PMID- 10915075
TI  - Changes in the composition of circulating CD8+ T cell subsets during acute
      epstein-barr and human immunodeficiency virus infections in humans.
AB  - In response to viral infection, unprimed naive CD8(+), major histocompatibility
      complex class I-restricted, virus-specific T cells clonally expand and
      differentiate into memory- and effector-type cells. Changes in CD8(+) subset
      distribution were studied in 17 subjects with acute human immunodeficiency virus
      type 1 infection and in 14 subjects with acute Epstein-Barr virus (EBV)
      infection, with combined CD45RO, CD27, and CD28 monoclonal antibodies. A vast
      expansion of memory-type CD45RO(+)CD27(+)CD8(+) T cells, with high expression of
      the cell-cycle marker Ki-67, was observed in both infections. Strikingly,
      CD45RO(+)CD27(+)CD28(-) cells increased >10-fold in acute viral infection and had
      high Ki-67 expression. In acute EBV infection, a substantial portion of the
      expanded T cells were EBV-peptide specific. These cells resided mainly in the
      CD45RO(+)CD27(+) subpopulation, with most in the CD27(+)CD28(-) subpopulation.
      Content of perforin expression, as a measure of cytotoxic capacity, was
      relatively low in the CD27(+)CD28(+) T cells and highest in the CD27(-)CD28(-)
      subpopulation.

PMID- 10915076
TI  - Acute sexually transmitted infections increase human immunodeficiency virus type
      1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts.
AB  - In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4
      years; this incubation time is specific to female sex workers. We studied the
      influence of acute sexually transmitted infections (STIs) on several immunologic
      parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV
      1-negative women sex workers who were followed for 1-5 months. Plasma cytokines,
      soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia
      were quantitated before, during, and after episodes of STI. Increases in
      interleukin (IL)-4, IL-6, IL-10, soluble tumor necrosis factor (TNF)-alpha, and
      viremia and a decline in CD4(+) T cell counts occurred during gonococcal
      cervicitis and returned to baseline after treatment. Increases in viremia
      correlated with increased IL-4 and decreased IL-6 concentrations. Similar changes
      were seen among women with acute pelvic inflammatory disease. Acute bacterial STI
      resulted in increased HIV-1 viremia. This may be mediated through increased
      inflammatory cytokines or through modulation of immune responses that control HIV
      1 viremia.

PMID- 10915077
TI  - High levels of tumor necrosis factor-alpha and interleukin-1beta in bacterial
      vaginosis may increase susceptibility to human immunodeficiency virus.
AB  - Bacterial vaginosis (BV) was identified recently as a cofactor that promotes
      sexual transmission of human immunodeficiency virus (HIV). This study was done to
      determine if interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha could
      be measured consistently in cervical secretions and if high levels of these
      cytokines were associated with BV. Secretions were obtained from 209 study
      subjects; most samples had detectable levels of TNF-alpha (84.2%) and IL-1beta
      (79.8%). BV was detected in 53 (27.0%) of 196 women. High cytokine levels were
      significantly associated with BV (adjusted odds ratio [AOR], 4.17; 95% confidence
      interval [CI], 1.69-10.30), oral contraceptive use (AOR, 2.78; 95% CI, 1.04
      7.48), and high leukocyte counts on vaginal smear (AOR, 1.18; 95% CI, 1.03-1.36).
      Since these cytokines could up-regulate local HIV replication through activation
      of the long terminal repeat promoter region, the association of BV with high
      levels of IL-1beta or TNF-alpha may partly explain the mechanism by which this
      risk factor enhances HIV transmission.

PMID- 10915078
TI  - Natural T, gammadelta, and NK cells in mycobacterial, Salmonella, and human
      immunodeficiency virus infections.
AB  - NK cells, gammadelta T cell antigen receptor chain-positive cells, and
      CD3(+)CD16/56(+) (natural T [NT]) cells are involved in innate immunity and
      immunoregulation; however, their role in clinical infection is not well defined.
      Cytofluorometric analysis was used to examine peripheral blood from bacteremic,
      nonbacteremic, and healthy human immunodeficiency virus (HIV)-positive and 
      negative persons in Malawi, Africa. Mycobacteremia was associated with a higher
      proportion of CD3(+)CD8(-) gammadelta cells (median, 16.6% vs. 0.7% for all other
      cells; P<.001), and Salmonella bacteremia was associated with a higher proportion
      of NT cells (4.3% vs. 2.2%; P=. 002). HIV plasma RNA levels were weakly
      positively correlated with NT cells (rs=.39; P=.002), NK cells (rs=.38; P=.003),
      and gammadelta cells (rs=.43; P<.001). Compared with patients who survived,
      patients who died had a higher percentage of NT cells (3.7% vs. 1. 9%; P=.017)
      and a higher percentage of NT cells that spontaneously produced interferon-gamma
      (2.4% vs. 1.2%; P=.035). The data support the clinical relevance of gammadelta
      and NT cells in mycobacterial, Salmonella, and HIV infections and of NT cells in
      mortality.

PMID- 10915079
TI  - Alcohol consumption by C57BL/6 mice is associated with depletion of lymphoid
      cells from the gut-associated lymphoid tissues and altered resistance to oral
      infections with Salmonella typhimurium.
AB  - Studies were done to test whether ethanol (ETOH) consumption alters resistance to
      mucosal and systemic infections by Salmonella typhimurium. S. typhimurium-immune
      and -nonimmune mice were fed 1 of 3 diets (an ETOH-containing liquid diet, an
      isocaloric liquid diet equal in volume to that of the ETOH-treated group, or
      laboratory chow) in a pair-feeding design and were infected orally or
      intravenously with S. typhimurium. The number of bacteria in spleen and liver and
      the effect of ETOH feeding and infection on the number of lymphoid cells in the
      gut-associated lymphoid tissues (GALT) were determined. ETOH feeding resulted in
      profound loss of GALT lymphoid cells and an increased number of Salmonella
      organisms in the intestines, liver, and spleen of infected nonimmune, but not of
      immune, mice. These data show that ETOH consumption in this model impairs host
      defense mechanisms that control mucosal infections and inhibits the mechanisms
      that control levels of bacteria in the central organs.

PMID- 10915080
TI  - Serotype distribution and antimicrobial resistance patterns of invasive isolates
      of Streptococcus pneumoniae: Alaska, 1991-1998.
AB  - From January 1991 through December 1998, a total of 1046 pneumococcal isolates
      were received from 23 laboratories participating in the statewide surveillance
      system. Of these, 1037 were recovered from normally sterile sites (blood and
      cerebrospinal and pleural fluid) and were available for serotyping and
      susceptibility testing. Ninety-two percent of these isolates were serotypes
      represented in the 23-valent pneumococcal polysaccharide vaccine. Serotypes in
      the 7-valent pneumococcal conjugate vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F)
      were recovered from 72% of Alaska Natives and 84% of non-Native children <5 years
      old with invasive disease. Statewide, 7.3% and 3.2% of isolates had intermediate
      and high levels of resistance to penicillin, respectively; 9.2% were resistant to
      erythromycin (minimal inhibitory concentration, >/=1 microg/mL) and 19% to
      trimethoprim/sulfamethoxazole (minimal inhibitory concentration, >/=4/76
      microg/mL). Twelve percent of invasive isolates were resistant to >/=2 classes of
      antibiotics; of these, serotype 6B accounted for 33%, and 63% were recovered from
      children <5 years old.

PMID- 10915081
TI  - C3 as substrate for adhesion of Streptococcus pneumoniae.
AB  - The ability of choline-binding protein A (CbpA) of Streptococcus pneumoniae to
      bind the third component of complement (C3) suggests possible interactions with
      opsonic C3 in the bloodstream or with C3 secreted by epithelial cells. The latter
      possibility was investigated by measuring C3 in supernatants of resting and
      cytokine-activated monolayers of type II pulmonary epithelial cells (A549 cells).
      Expression of C3 on the epithelial cell surface was confirmed by
      immunofluorescence. Epithelially produced C3 bound to CbpA, as determined by
      Western blot test. cbpa(-) mutants and lysates therefrom failed to bind C3, were
      completely deficient in adhesion to a matrix in which C3 was the sole substrate,
      and demonstrated a moderate yet significant decrease in adhesion to type II
      pulmonary epithelial cells. These results confirm the interaction of the
      pneumococcal protein CbpA and its substrate, C3, in 2 in vitro models of
      adhesion.

PMID- 10915082
TI  - Short-course antibiotic treatment of 4782 culture-proven cases of group A
      streptococcal tonsillopharyngitis and incidence of poststreptococcal sequelae.
AB  - A large-scale study with a 1-year follow-up was performed to compare 10 days of
      penicillin V with a short-course treatment (5 days) of other oral antibiotics in
      the treatment of group A beta-hemolytic streptococcus (GABHS)
      tonsillopharyngitis, to evaluate the efficacy and the incidence of
      poststreptococcal sequelae. The clinical response rates after completion of
      therapy were 94.5% in the 5-day group and 93.4% in the penicillin group (P<.001,
      equivalence test). The GABHS eradication rates were 83.3% in the 5-day group and
      84.4% in the penicillin group (P=.022, equivalence test). Poststreptococcal
      sequelae were rare (5 patients) and did not occur in the context of this study.
      The efficacy of 5-day antibiotic regimens was equivalent to 10 days of penicillin
      V, but resolution of clinical symptoms was faster in the 5-day group (P<.001,
      Fisher's exact test). Recurrent tonsillopharyngitis occurs more frequently after
      treatment with penicillin (P=.03, Fisher's exact test).

PMID- 10915083
TI  - Selection of antibiotic-resistant bacterial mutants: allelic diversity among
      fluoroquinolone-resistant mutations.
AB  - To obtain a general framework for understanding selection of antibiotic-resistant
      mutants, allelic diversity was examined with about 600 fluoroquinolone-resistant
      mutants of mycobacteria. Selection at low fluoroquinolone concentration produced
      many low-level resistance mutants. Some of these contained mutations that
      conferred unselected antibiotic resistance; none contained alterations in the
      quinolone-resistance-determining region of the GyrA protein, the principal drug
      target. As selection pressure increased, a variety of GyrA variants became
      prevalent. High concentrations of antibiotic reduced the variety to a few types,
      and eventually a concentration was reached at which no mutant was recovered. That
      concentration defined a threshold for preventing the selection of resistance. The
      pattern of variants selected, which was also strongly influenced by antibiotic
      structure, readily explained the variants present in clinical isolates. Thus,
      resistance arises from selection of mutants whose identity depends on drug
      concentration and structure, both of which can be manipulated to restrict
      selection.

PMID- 10915084
TI  - In vivo neutrophil dysfunction in cirrhotic patients with advanced liver disease.
AB  - Bacterial infections are frequent, life-threatening complications in cirrhotic
      patients. This study investigated in vivo neutrophil migration and phagocytic
      activity in cirrhotic patients with advanced liver disease, in liver transplant
      recipients, and in healthy volunteers, by use of the skin window technique.
      Complement receptor type III (CR3) expression was also measured in blood and
      elicited neutrophils. Neutrophil migration to skin windows and neutrophil in vivo
      phagocytosis of heat-killed Escherichia coli were significantly decreased in
      cirrhotic patients compared with healthy controls. Neutrophil migration and
      phagocytosis were decreased in cirrhotic patients with previous episodes of
      bacterial infection compared with noninfected patients. Expression of CR3 in
      circulating neutrophils was significantly higher in cirrhotic patients, whereas
      it was significantly reduced in elicited neutrophils of cirrhotic patients with
      previous bacterial infection. These data suggest that deficient neutrophil
      recruitment to the infection site and impaired phagocytic activity may contribute
      to bacterial infections in cirrhotic patients with advanced liver disease.

PMID- 10915085
TI  - Immune complexes from serum of patients with lyme disease contain Borrelia
      burgdorferi antigen and antigen-specific antibodies: potential use for improved
      testing.
AB  - We report sequestration of specific IgM anti-Borrelia burgdorferi (Bb) and Bb
      antigens within immune complexes (ICs) isolated from serum of patients with Lyme
      disease (LD). The relative enrichment in specific IgM measured by ELISA was
      apparent, even after correcting for differences in total IgM concentration in
      serum versus ICs. Immunoblot demonstrated that ICs contained antibodies against
      specific Bb proteins, whereas reactivity was absent or significantly lessened in
      unprocessed serum. This is the first study to show ICs containing Bb antigen
      identified by immunoblot with anti-Bb monoclonal antibody. ICs may be a useful
      source of antigen and antibody for development of more-accurate testing for LD.

PMID- 10915086
TI  - Quantitative Chlamydia trachomatis cultures: correlation of chlamydial inclusion
      forming units with serovar, age, sex, and race.
AB  - The number of inclusion-forming units (IFUs) observed in quantitative chlamydial
      cultures may be a surrogate for infectivity or transmissibility. Therefore, we
      conducted a cross-sectional study of 11,034 patients with Chlamydia trachomatis
      infection who presented to the Seattle-King County public health department
      clinics between 1988 and 1996, to determine relationships between the number of
      IFUs observed in culture and sex, age, race, and serovar class. Of the 11,034
      cases of infection we studied, 6801 (62%) were cervical infections in women, and
      4233 (38%) were urethral infections in men. The median count was 450 IFU for
      women and 72 IFU for men (P<.001). Overall, both men and women infected with B
      class serovars had significantly higher IFU counts than did those infected with C
      class serovars (P<.001). The median IFU count fell consistently with increasing
      age for both women (625 IFU for those <16 years old to 185 IFU for those >30
      years old; P<.001) and men (210 IFU for those <16 years old to 40.5 IFU for those
      >30 years old; P<.001). We found, by use of multiple regression analysis, that
      sex, age, race, and serovar class remained independently related to IFU count,
      with counts being highest among young white women infected with B-class serovars.

PMID- 10915087
TI  - Amphotericin B combined with itraconazole or fluconazole for treatment of
      histoplasmosis.
AB  - To investigate the efficacy of combined treatment with fluconazole (Flu) and
      amphotericin B (AmB) for Histoplasma capsulatum meningitis, MICs were determined
      for 10 clinical isolates, following National Committee for Clinical Laboratory
      Standards guidelines. Weak synergy was observed for 6 of the 10 isolates. For the
      in vivo models, mice either were sham treated or were given Flu (75 mg/kg/day),
      AmB (2 mg/kg every other day), itraconazole (Itra; 75 mg/kg/day), AmB+Flu, or
      AmB+Itra. Following infection with 5x105 yeasts, Flu antagonized AmB's reduction
      of fungal burden without reducing its effect on survival. When in vivo antagonism
      was reproduced following infection with 1x104 yeasts, a higher fungal burden was
      observed in the lungs. Itra had no effect on AmB's activity and was more
      effective than Flu for clearance of fungal burden. These findings caution against
      use of AmB+Flu for treatment of histoplasmosis, but studies of the effect of
      treatment on the fungal burden in the brain are needed to assess combination
      therapy for meningitis.

PMID- 10915088
TI  - Pneumocystis carinii mutations are associated with duration of sulfa or sulfone
      prophylaxis exposure in AIDS patients.
AB  - This study was conducted to determine whether Pneumocystis carinii
      dyhydropteroate synthase (DHPS) gene mutations in AIDS patients with P. carinii
      pneumonia (PCP) are affected by duration of sulfa or sulfone prophylaxis and
      influence response to sulfa or sulfone therapy. The P. carinii DHPS genes from 97
      AIDS patients with PCP between 1991 and 1999 from 4 medical centers were
      amplified, using polymerase chain reaction (PCR), and sequenced. Mutations were
      observed in 76% of isolates from patients exposed to sulfa or sulfone prophylaxis
      compared with 23% of isolates from patients not exposed (P=.001). Duration of
      prophylaxis increased the risk of mutations (relative risk [RR] for each exposure
      month, 1.06; P=.02). Twenty-eight percent of patients with mutations failed sulfa
      or sulfone treatment; mutations increased the risk of sulfa or sulfone treatment
      failure (RR, 2.1; P=0.01). Thus, an increased duration of sulfa or sulfone
      prophylaxis increases the chance of developing a P. carinii mutation. The
      majority of patients with mutations respond to sulfa or sulfone therapy.

PMID- 10915089
TI  - Frequent umbilical cord-blood and maternal-blood infections with Plasmodium
      falciparum, P. malariae, and P. ovale in Kenya.
AB  - The prevalence of malaria infection in 102 paired maternal-blood and umbilical
      cord-blood samples was assessed by microscopy and polymerase chain reaction (PCR)
      in a holoendemic area in Kenya. Plasmodium falciparum single-species infection
      was detected in maternal peripheral blood (3.4%), whereas microscopy indicated
      that no Plasmodium species were in cord blood. In contrast, maternal-blood
      samples showed a PCR prevalence of 48% for P. falciparum, 25% for P. malariae,
      and 24% for P. ovale, and cord-blood samples showed a PCR prevalence of 32%, 23%,
      and 21%, respectively. Although mothers with mixed-species infections were more
      likely to have offspring infected with mixed species, the specific malaria
      species were discordant in paired maternal- and cord-blood samples. Triple
      species infections were observed in 11 cord- and maternal-blood samples at a 5.5
      fold greater frequency than expected. These findings indicate that Plasmodium
      species infections in cord blood are common, occur at lower densities, and may be
      acquired before parturition.

PMID- 10915090
TI  - Strong association of interleukin-6 and lipopolysaccharide-binding protein with
      severity of adverse reactions after diethylcarbamazine treatment of
      microfilaremic patients.
AB  - To assess the involvement of inflammatory mediators in the development of adverse
      reactions in filarial patients undergoing treatment, 29 microfilaremic subjects
      were treated with diethylcarbamazine (DEC). Before and at serial time points
      after initiation of treatment, plasma levels of inflammatory mediators and DEC
      were measured, and adverse reactions were recorded. Patients experienced no or
      mild, moderate, or severe adverse reactions. Increasing pretreatment
      microfilarial counts were associated with escalating severity of adverse
      reactions. Plasma concentrations of DEC were not different among patients
      suffering from varying degrees of illness. Interleukin (IL)-6, IL-10,
      lipopolysaccharide-binding protein (LBP), and soluble tumor necrosis factor
      receptors (sTNF-Rs) increased after treatment. IL-6 and LBP, however, showed the
      strongest association with adverse reactions. Increasing levels of these
      molecules were closely correlated with the mounting severity of adverse
      reactions, which raises the possibility that they play an important role in
      systemic inflammation that arises after DEC treatment of filarial patients.

PMID- 10915091
TI  - A Leishmania homologue of receptors for activated C-kinase (LACK) induces both
      interferon-gamma and interleukin-10 in natural killer cells of healthy blood
      donors.
AB  - Natural killer (NK) cells from individuals unexposed to Leishmania organisms
      proliferate with high interferon (IFN)-gamma secretion in response to crude
      Leishmania antigen preparations. In an attempt to identify the molecules that
      induce blood cells to proliferate and to secrete cytokines, we tested the effect
      of a 36-kDa Leishmania homologue of receptors for activated C-kinase (LACK) on
      peripheral blood mononuclear cells from unexposed individuals. Mainly CD8(+) and
      NK cells proliferated in response to LACK. At both the mRNA and soluble protein
      level, the main sources for LACK-induced IFN-gamma and interleukin (IL)-10 were T
      and NK cells. Furthermore, in the presence of anti-major histocompatibility
      complex (MHC) class II antibody, there was inhibition of LACK responses in both
      CD4(+) and CD16/56(+) cells, with a marked decrease in IFN-gamma but with an
      increase in IL-10 production. We conclude that the response to LACK is part of
      the response to Leishmania organisms in unexposed donors described elsewhere.
      That this NK-dominated response is MHC class II sensitive, whether through a
      direct or indirect effect, is discussed.

PMID- 10915092
TI  - Biological considerations in the development of a human immunodeficiency virus
      vaccine.
AB  - Over the last 12 years, many human immunodeficiency virus (HIV) vaccine
      candidates have been tried in humans, with disappointing results. In particular,
      recombinant envelope proteins have failed to elicit strong cellular immune
      responses or neutralizing antibody against many wild-type isolates of HIV-1.
      Attenuated strains of simian immunodeficiency virus (SIV), although capable of
      protecting against virulent strains of SIV, often retain residual pathogenicity.
      These difficulties suggest that it will be necessary to address a number of
      biological questions that underpin the rational development of an AIDS vaccine:
      (1) Will natural infection with HIV protect against superinfection? (2) Is
      partial protection induced by an HIV vaccine adequate to prevent AIDS? (3) What
      are the immune correlates of protection for an AIDS vaccine? (4) Will a monotypic
      HIV-1 vaccine confer cross-clade immunity? (5) Is mucosal immunity important for
      an effective AIDS vaccine? (6) Is there a rationale for therapeutic immunization?
      Ongoing research that is addressing these questions should lead to the
      formulation of a safe and effective AIDS vaccine.

PMID- 10915093
TI  - Increased liver decompensation risk with atypical hepatitis C virus antibody
      levels.
AB  - Knowledge of serum markers of liver decompensation would facilitate care of
      patients with hepatitis C virus (HCV) and human immunodeficiency virus (HIV)
      infections. HCV load and anti-c33c and anti-NS5 levels did not distinguish 28 HCV
      and HIV-positive predecompensation patients from 28 matched control patients,
      whereas more patients than controls had high anti-c100(p) and low anti-c22(p). In
      multivariate analysis, decompensation was associated with high anti-c100(p) titer
      (>/=1:4050; odds ratio [OR], 3. 4; 95% confidence interval [CI], 1.1-11.5) and
      low anti-c22(p) (<1:36,450; OR, 3.0; 95% CI, 1.0-10.2) and with antibody band
      strength at 1:50 dilution (anti-c100[p] OR, 7.0; 95% CI, 1. 7-48.9; anti-c22[p]
      OR, 7.1; 95% CI, 1.7-49.2). With high anti-c100(p) or low anti-c22(p),
      sensitivity for decompensation was 86%-96% and specificity was 21%-36%; with both
      markers, sensitivity was 29%-32% and specificity was 93%-96%. Although the
      mechanisms for these associations are unknown, if these findings are verified in
      other populations, anti-c100(p) and anti-c22(p) might be valuable surrogate
      markers for liver decompensation risk.

PMID- 10915094
TI  - Persistence of human papillomavirus type 16 infection is associated with lack of
      cytotoxic T lymphocyte response to the E6 antigens.
AB  - Our cross-sectional study suggested that cytotoxic T lymphocyte (CTL) responses
      have a protective effect in squamous intraepithelial lesion (SIL) development.
      More CTL responses in women with human papillomavirus type 16 (HPV 16) infection
      without SILs than with SILs were detected. In the current longitudinal study, the
      role of CTL in clearing HPV 16 infection in women without SILs was investigated.
      Women with HPV 16 infection (n=51) were enrolled, along with HPV 16-negative
      control women (n=3). Twenty-two (55%) of 40 women who cleared HPV 16 infection
      had an E6 CTL response at least once, compared with none of 9 women who had HPV
      16 persistence (P=.003). Such a difference was not demonstrated for E7; 25 (63%)
      of 40 women who cleared HPV 16 infection responded, versus 5 (56%) of 9 women
      with persistence (P=.720). It appears that lack of response to E6 is important in
      the persistence of HPV 16 infection.

PMID- 10915095
TI  - Once-daily combination therapy with emtricitabine, didanosine, and efavirenz in
      human immunodeficiency virus-infected patients.
AB  - The safety and efficacy of a once-daily regimen that combines emtricitabine,
      didanosine, and efavirenz was studied among 40 previously untreated human
      immunodeficiency virus (HIV)-infected patients. The median plasma HIV RNA level
      was 4.77 log(10) copies/mL at baseline and decreased by a median of 3.5 log(10)
      copies/mL at 24 weeks, with 98% and 93% of patients achieving plasma HIV RNA
      levels <400 and <50 copies/mL, respectively. The median CD4 cell count was 373
      cells/microL at baseline and increased by a median of 159 cells/microL at week
      24. The most common treatment-related adverse events were mild to moderate
      central nervous system symptoms (73% of patients), diarrhea (33%), rashes (10%),
      and biochemical abnormalities. Adverse reactions led to permanent drug
      discontinuation in only 1 patient. The once-daily combination therapy of
      emtricitabine, didanosine, and efavirenz was safe and demonstrated strong
      antiviral and immunologic effects that lasted for the 24-week period of the
      study.

PMID- 10915096
TI  - Plasma human immunodeficiency virus (HIV) type 1 RNA load in men and women with
      advanced HIV-1 disease.
AB  - Several studies of patients infected with human immunodeficiency virus (HIV) type
      1 have suggested that women have lower plasma HIV-1 RNA levels than men, even
      when controlling for CD4 T cell levels. A cross-sectional analysis was performed
      in 494 patients (21% of whom were women) who enrolled in a prospective study of
      anemic HIV-1-infected patients requiring transfusion. The median CD4 T cell count
      and plasma HIV-1 RNA levels were 15 cells/microL and 4.83 log(10) copies/mL
      (67,350 copies/mL), respectively. In unadjusted analyses, women had slightly
      higher mean log HIV-1 RNA titers than men (0.19 log(10) higher copies/mL; 95%
      confidence interval, -0.05 to 0.44; P=.11). Adjustment for CD4 T cell count, race
      or ethnicity, injection drug use, and age yielded a smaller sex difference (0.13
      log(10) copies/mL higher in women; P=.28). In this population of patients with
      very advanced HIV disease, there is no evidence that women have lower HIV-1 RNA
      levels than men.

PMID- 10915097
TI  - A fusion inhibitor (FP-21399) for the treatment of human immunodeficiency virus
      infection: a phase I study.
AB  - FP-21399 is a bis(disulfonaphthalene) derivative that prevents human
      immunodeficiency virus (HIV) infection of uninfected cells by blocking entry of
      the virus. FP-21399 shows an affinity for lymph nodes. In this phase I study, FP
      21399 was administered intravenously over 1 h as a single dose (0.9, 1.7, 2.8,
      and 4.2 mg/kg) or as a once-weekly infusion (1, 2, and 3 mg/kg) for 4 consecutive
      weeks to 34 HIV-1 infected patients with CD4(+) cell counts of 50-400
      cells/microL. Concomitant antiretroviral therapy was permitted but not required.
      The most frequent adverse events involved the transient, dose-dependent
      appearance of drug- or metabolite-related color in the urine and skin. Plasma
      drug levels were linear with dose. The drug was cleared, with an elimination half
      life of 4 h and a terminal half-life of 1.5-2 days; the terminal half-life
      represented redistribution and clearance from tissues. FP-21399 administered
      weekly for 4 weeks was well tolerated. Further studies are necessary to define
      the role of this fusion inhibitor in the treatment of HIV infection.

PMID- 10915098
TI  - Risk for preventable opportunistic infections in persons with AIDS after
      antiretroviral therapy increases CD4+ T lymphocyte counts above prophylaxis
      thresholds.
AB  - To determine incidence and risk for preventable opportunistic infections
      (Pneumocystis carinii pneumonia [PCP] and disseminated Mycobacterium avium
      complex [MAC] infection) in persons whose CD4(+) T lymphocyte counts had
      increased by >/=100 cells/microL to exceed the threshold of risk and in persons
      whose CD4(+) counts had never dropped below the threshold of risk, we analyzed
      data collected during the period 1990-1998 in the Adult/Adolescent Spectrum of
      HIV (Human Immunodeficiency Virus) Disease Project. Using a counting-process
      formulation of the Cox model, we analyzed observation time in these 2 groups for
      persons who were prescribed antiretroviral therapy but not prophylaxis. The
      incidences of the infections were low for patients whose CD4(+) count rose above
      the threshold of risk (PCP, 0.6 cases per 100 person-years [PY]; MAC, 1. 0 cases
      per 100 PY) and not higher than in persons whose CD4(+) counts had not decreased
      below these thresholds, which suggests that discontinuation of primary
      prophylaxis for opportunistic infections may be considered for some patients.

PMID- 10915099
TI  - Transmission of the agent of human granulocytic ehrlichiosis by Ixodes
      spinipalpis ticks: evidence of an enzootic cycle of dual infection with Borrelia
      burgdorferi in Northern Colorado.
AB  - Previous work described an enzootic cycle of Borrelia burgdorferi sensu lato
      (hereafter referred to as B. burgdorferi) maintained by the rodent Neotoma
      mexicana and the tick Ixodes spinipalpis in northern Colorado. We investigated
      the incidence of coinfection among rodents with the agent of human granulocytic
      ehrlichiosis (aoHGE). aoHGE was detected in 23.5% of 119 rodent spleens examined.
      Biopsy results indicated that 78 (65.5%) of the 119 rodents were positive for B.
      burgdorferi, whereas 22 (78.5%) of the 28 animals that harbored aoHGE were also
      infected with B. burgdorferi. In 14 of 25 I. spinipalpis tick pools, aoHGE was
      detected by amplifying both the 16s rRNA and p44 gene of aoHGE. The ability of I.
      spinipalpis to transmit aoHGE was examined in C3H/HeJ mice. aoHGE was detected in
      their blood 5 days after I. spinipalpis infestation. This study confirms that
      both B. burgdorferi and aoHGE can be transmitted by I. spinipalpis ticks and that
      there is a high incidence of coinfection in rodents, predominantly Peromyscus
      maniculatus and N. mexicana, that inhabit the foothills of northern Colorado.

PMID- 10915100
TI  - Cytolethal distending toxin in avian and human isolates of Helicobacter pullorum.
AB  - Helicobacter pullorum has been isolated from the feces and livers of poultry and
      is associated with human gastroenteritis. Discrimination of this organism from
      other enterohepatic Helicobacter species and Campylobacter species has proven
      difficult. H. pullorum from both avian and human clinical sources has DNA
      sequence homology and cytotoxic activity that represent a new member of the
      cytolethal distending toxin (CDT) family of bacterial toxins. CDT is a potential
      virulence factor in H. pullorum that may serve as a distinguishing phenotype and
      aid in identification of this organism in veterinary and human clinical samples.

PMID- 10915101
TI  - Sequence variations in the genes encoding dihydropteroate synthase and
      dihydrofolate reductase and clinical response to sulfadoxine-pyrimethamine in
      patients with acute uncomplicated falciparum malaria.
AB  - Mutations in dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR)
      are associated with in vitro resistance to sulfadoxine and pyrimethamine,
      respectively. The response of 75 patients to sulfadoxine-pyrimethamine was
      determined, and the genes of the corresponding Plasmodium falciparum isolates
      were sequenced. Of 12 different unmixed allelic combinations, the triple dhfr
      mutation Asn-108/Arg-59/Ile-51 was observed in all patients responding with early
      treatment failure. Some, but not all, patients with an adequate clinical response
      also harbored isolates with the triple dhfr mutation. Higher initial parasitemia
      and fever distinguished these 2 patient groups. The dhps genotype apparently had
      no influence on the clinical outcome. The other dhfr alleles with 1 or 2
      mutations and the wild-type allele were found in patients with an adequate
      clinical response. The triple dhfr mutation is one of the genetic determinants
      associated with in vivo resistance to sulfadoxine-pyrimethamine.

PMID- 10915102
TI  - The mechanisms of parasite clearance after antimalarial treatment of Plasmodium
      falciparum malaria.
AB  - Studies were conducted to determine how malaria parasites are cleared from the
      blood after antimalarial treatment. Neither artesunate nor quinine decreased
      parasitized red cell deformability or increased antibody binding. In acute
      falciparum malaria, ring-infected erythrocyte surface antigen (RESA) was observed
      in erythrocytes without malaria parasites (RESA-red blood cell [RBC]), indicating
      prior parasitization. In uncomplicated malaria, RESA-RBC numbers increased
      significantly (P=.002) within 24 h of starting artesunate but rose much more
      slowly (7 days) after quinine treatment. In severe malaria, RESA-RBC increased
      significantly (P=. 001) within hours of starting artesunate but not with quinine
      treatment (P=.43). RESA-RBCs were not produced after drug treatment of malaria
      parasite cultures in vitro. Rapid malaria parasite clearance after treatment with
      artemisinin derivatives results mainly from the extraction of drug-affected
      parasites from host erythrocytes-presumably by the spleen. This explains why the
      fall in hematocrit after treatment of hyperparasitemia is often less than that
      predicted from loss of parasitized cells.

PMID- 10915103
TI  - Immunological and clinical evaluation of chagasic patients subjected to
      chemotherapy during the acute phase of Trypanosoma cruzi infection 14-30 years
      ago.
AB  - We recently evaluated the in vitro proliferative response and interferon (IFN)
      gamma production of peripheral blood mononuclear cells from a group of 25 people
      who were treated for Chagas' disease during the acute phase of Trypanosoma cruzi
      infection and followed up for a period of 14-30 years. On the basis of the
      parasitological and serological tests, the individuals were classified as cured
      (C), dissociated, or not cured (NC). Members of group C (the group without
      cardiac alterations) presented significantly stronger proliferative response
      against the parasite antigens, with secretion of high levels of IFN-gamma in
      comparison with the NC group, raising a question about the role of this cytokine
      in the curing of human T. cruzi infection. Severe cardiac alterations were
      observed only in 1 of 25 patients, which suggests that treatment benefited the
      patients.

PMID- 10915104
TI  - Tumor necrosis factor-alpha increased production during thalidomide treatment in
      patients with tuberculosis and human immunodeficiency virus coinfection.

PMID- 10915105
TI  - Reply

PMID- 10915107
TI  - Adolescent mental health and risky sexual behaviour. Young people need health
      care that covers psychological, sexual, and social areas.

PMID- 10915109
TI  - Training overseas doctors in the United Kingdom. They must be given accurate
      information about their job prospects.

PMID- 10915108
TI  - Thiazolidinediones for type 2 diabetes. New agents reduce insulin resistance but
      need long term clinical trials.

PMID- 10915110
TI  - Molecular stool screening for colorectal cancer. Using DNA markers may be
      beneficial, but large scale evaluation is needed.

PMID- 10915111
TI  - Which clinical studies provide the best evidence? The best RCT still trumps the
      best observational study.

PMID- 10915112
TI  - MPs call for far reaching reforms to mental health services.

PMID- 10915113
TI  - Executives fly the koop.com

PMID- 10915114
TI  - Gynaecologist struck off the medical register

PMID- 10915115
TI  - Women doctors earn $63000 less than male counterparts

PMID- 10915117
TI  - UK licence for cisapride suspended

PMID- 10915116
TI  - In brief

PMID- 10915118
TI  - Cancer drug may cause heart failure.

PMID- 10915120
TI  - $1bn drug deal creates debt for "tomorrow's AIDS orphans"

PMID- 10915119
TI  - Relatives of Shipman victims win first round in fight for open inquiry.

PMID- 10915122
TI  - Lumpectomy as good as mastectomy for tumours up to 5 cm

PMID- 10915121
TI  - Better screening needed for sickle cell and thalassaemia

PMID- 10915123
TI  - Irish blood service sues its former medical consultant

PMID- 10915124
TI  - US judge approves distribution of marijuana

PMID- 10915125
TI  - Concern mounts over female genital mutilation.

PMID- 10915126
TI  - Psychiatric disorders and risky sexual behaviour in young adulthood: cross
      sectional study in birth cohort.
AB  - OBJECTIVE: To determine if risky sexual intercourse, sexually transmitted
      diseases, and sexual intercourse at an early age are associated with psychiatric
      disorder. DESIGN: Cross sectional study of a birth cohort at age 21 years with
      assessments presented by computer (for sexual behaviour) and by trained
      interviewers (for psychiatric disorder). SETTING: New Zealand in 1993-4.
      PARTICIPANTS: 992 study members (487 women) from the Dunedin multidisciplinary
      health and development study. Complete data were available on both measures for
      930 study members. MAIN OUTCOME MEASURES: Psychiatric disorders (anxiety,
      depression, eating disorder, substance dependence, antisocial disorder, mania,
      schizophrenia spectrum) and measures of sexual behaviour. RESULTS: Young people
      diagnosed with substance dependence, schizophrenia spectrum, and antisocial
      disorders were more likely to engage in risky sexual intercourse, contract
      sexually transmitted diseases, and have sexual intercourse at an early age
      (before 16 years). Unexpectedly, so were young people with depressive disorders.
      Young people with mania were more likely to report risky sexual intercourse and
      have sexually transmitted diseases. The likelihood of risky behaviour was
      increased by psychiatric comorbidity. CONCLUSIONS: There is a clear association
      between risky sexual behaviour and common psychiatric disorders. Although the
      temporal relation is uncertain, the results indicate the need to coordinate
      sexual medicine with mental health services in the treatment of young people.

PMID- 10915128
TI  - To coin a phrase

PMID- 10915127
TI  - Efficacy and harm of pharmacological prevention of acute mountain sickness:
      quantitative systematic review.
AB  - OBJECTIVE: To quantify efficacy and harm of pharmacological prevention of acute
      mountain sickness. DATA SOURCES: Systematic search (Medline, Embase, Cochrane
      Library, internet, bibliographies, authors) in any language, up to October 1999.
      STUDY SELECTION: Randomised placebo controlled trials. DATA EXTRACTION:
      Dichotomous data on efficacy and harm from 33 trials (523 subjects received 13
      different interventions, 519 a placebo). DATA SYNTHESIS: At above 4000 m the mean
      incidence of acute mountain sickness with placebo was 67% (range 25% to 100%);
      incidence depended on the rate of ascent, but not on the altitude or the mode of
      ascent. Across all ascent rates, dexamethasone 8-16 mg prevented acute mountain
      sickness (relative risk 2.50 (95% confidence interval 1.71 to 3.66); number
      needed to treat (NNT) 2.8 (2.0 to 4.6)), without evidence of dose responsiveness.
      Acetazolamide 750 mg was also efficacious (2.18 (1.52 to 3.15); NNT 2.9 (2.0 to
      5.2)), but 500 mg was not. In two trials, adverse reaction (including depression)
      occurred after dexamethasone was stopped abruptly (4.45 (1.08 to 18); NNT 3.7
      (2.5 to 6.9)). With acetazolamide, paraesthesia (4.02 (1.71 to 9.43); NNT 3.0
      (2.0 to 6.0)) and polyuria (4.24 (1.92 to 9.37); NNT 3.6 (2.5 to 6.2)) were
      reported. Data were sparse on nifedipine, frusemide (furosemide),
      dihydroxyaluminium-sodium, spironolactone, phenytoin, codeine, phenformin,
      antidiuretic hormone, and ginkgo biloba. CONCLUSIONS: At above 4000 m, with a
      high ascent rate, fewer than three subjects need to be treated with prophylactic
      dexamethasone 8-16 mg or acetazolamide 750 mg for one subject not to experience
      acute mountain sickness who would have done so had they all received a placebo.
      Acetazolamide 500 mg does not work.

PMID- 10915129
TI  - Association of polymorphism of human alpha oestrogen receptor gene with coronary
      artery disease in men: a necropsy study.

PMID- 10915130
TI  - Early neonatal mortality, asphyxia related deaths, and timing of low risk births
      in Hesse, Germany, 1990-8: observational study.

PMID- 10915131
TI  - Atrial fibrillation associated with sumatriptan.

PMID- 10915133
TI  - Plague in glasgow

PMID- 10915132
TI  - A prescription for improvement? An observational study to identify how general
      practices vary in their growth in prescribing costs.
AB  - OBJECTIVE: To identify how some general practices have low growth in prescribing
      costs relative to other practices. DESIGN: Observational study. SETTING: Trent
      region of England. PARTICIPANTS: 162 general practices: 54 with low growth in
      prescribing costs, 54 with average increases in costs, and 54 with large
      increases in costs. MAIN OUTCOME MEASURES: Changes in prescribing costs in
      therapeutic categories in which it has been suggested that savings can be made.
      RESULTS: There were significant differences between the three groups of practices
      in terms of their changes in prescribing costs for almost all the variables
      studied. For the group of practices with lowest growth in costs the most
      important factors were reducing numbers of prescription items and costs per item;
      relatively low growth in the costs of "new and expensive" drugs; increasing
      generic prescribing; and reducing costs for modified release products. This group
      of practices did not increase costs as much as the others for lipid lowering
      drugs (P=0.012) and hormone replacement therapy (P=0. 007). The practices with
      the greatest increases in costs had particularly large increases for proton pump
      inhibitors, selective serotonin reuptake inhibitors, and modified release
      products. Compared with the other groups these practices had larger increases in
      costs for "expensive hospital initiated drugs" (P=0.009). CONCLUSION: General
      practices vary in their growth in prescribing costs in many ways, with growth in
      costs for "new and expensive" drugs being particularly important.

PMID- 10915135
TI  - Great aunt rose

PMID- 10915136
TI  - Scientists should die at 60

PMID- 10915134
TI  - Recent advances. Medical ethics.

PMID- 10915137
TI  - Horse allergy in children.

PMID- 10915139
TI  - Greek and latin useless for doctors

PMID- 10915138
TI  - ABC or oral health. Improving occlusion and orofacial aesthetics: orthodontics.

PMID- 10915140
TI  - Outcomes studies of drug induced ulcer complications: do we need them and how
      should they be done?

PMID- 10915141
TI  - Peace building through health initiatives.

PMID- 10915143
TI  - Don't tell the patient: behind the drug safety Net

PMID- 10915142
TI  - Obituaries

PMID- 10915144
TI  - Cancer: the evolutionary legacy

PMID- 10915145
TI  - The meat business: devouring a hungry planet

PMID- 10915146
TI  - Accessing ethical information

PMID- 10915147
TI  - Netlines

PMID- 10915148
TI  - What is the future for training overseas graduates?

PMID- 10915150
TI  - Blemished, unsprayed plums

PMID- 10915149
TI  - Gourmets

PMID- 10915152
TI  - Prevention of acute mountain sickness depends on ascent rate and drug dose

PMID- 10915151
TI  - Psychiatric disorders predispose to risky sexual behaviour

PMID- 10915153
TI  - Long allele alpha oestrogen receptor genotype may increase risk of coronary
      artery disease

PMID- 10915154
TI  - Early neonatal mortality and asphyxia related deaths are greater for night births

PMID- 10915155
TI  - General practices use a wide variety of methods for controlling their prescribing
      costs

PMID- 10915156
TI  - Reliance on endoscopy makes NSAID studies unreliable

PMID- 10915157
TI  - Leadership and motivation

PMID- 10915158
TI  - Good news for our journal liver transplantation

PMID- 10915159
TI  - Molecular biology of hepatitis C infection.
AB  - Hepatitis C infection (HCV) is an emerging epidemic. Liver specialists are
      managing this disease with limited scientific information about the underlying
      pathogenesis and treatment. The current review offers a molecular dissection of
      infection, a snapshot of the HCV life cycle, and emerging strategies for
      antiviral therapy.

PMID- 10915160
TI  - Prolonged rewarming time during allograft implantation predisposes to recurrent
      hepatitis C infection after liver transplantation.
AB  - The majority of patients undergoing orthotopic liver transplantation (OLT) have
      end-stage liver disease secondary to hepatitis C virus (HCV) infection. Although
      OLT does not cure the disease and recurrent virus is present in all patients,
      relatively few patients with recurrent viremia develop clinical disease. When the
      disease recurs, however, the results can be devastating. Factors associated with
      increased risk for recurrent HCV disease remain controversial. We hypothesized
      that preservation injury may predispose to the severity of HCV disease after OLT.
      We reviewed our series of OLTs performed for HCV cirrhosis between January 1994
      and December 1998 (n = 56; 62 transplants). Patients were grouped according to
      the severity of recurrent hepatitis C. Group 1 had no or mild HCV disease (n =
      36), and group 2 had moderate to severe HCV disease (n = 20). The duration of
      ischemic rewarming during graft implantation was significantly associated with
      the severity of recurrent hepatitis C (P <.04). The estimated chances of severe
      disease within the first year post-OLT after 30, 60, or 90 minutes of ischemic
      rewarming time were 19%, 40%, and 65%, respectively. Cold ischemia time,
      transaminase levels, and prothrombin time did not correlate with the severity of
      hepatitis C. In conclusion, our data suggest that the duration of ischemic
      rewarming predisposes to severe recurrent hepatitis C. This finding warrants the
      investigation of the pathogenesis of recurrent HCV disease after ischemic injury.
      Reduction of rewarming time should be stressed in OLT, particularly in patients
      with HCV cirrhosis.

PMID- 10915161
TI  - Hepatitis C recurrence after liver transplantation.

PMID- 10915162
TI  - Extensive use of split liver for pediatric liver transplantation: a single-center
      experience.
AB  - The results of the extensive use of in situ liver splitting in a pediatric liver
      transplant program are presented. All referred donors were considered for split
      liver, and when the donor-recipient body weight ratio (DRWR) was greater than 2,
      the grafts were split. A modified split-liver technique was adopted when the DRWR
      was 2 or less. Eighty liver procurements were attempted and 72 (90%) were
      performed, enabling 65 children to receive 42 split, 22 whole, and 8 reduced-size
      livers. The right portions of the grafts were transplanted by other centers into
      adults. Median patient waiting time was 22 days, with no mortality on the waiting
      list. After a median follow-up of 14 months, overall patient and graft survival
      rates were 85% and 81%, respectively. Fifty-eight children received a single
      allograft, whereas 7 children required retransplantation. Two-year actuarial
      survival rates were 85% for split-liver recipients, 84% for whole-liver
      recipients, and 67% for reduced-size liver recipients. Vascular complications
      developed in 18% of the patients, with no difference among the 3 groups with
      different technique. Biliary complications developed in 25% of the children,
      mainly in reduced-size and split-liver recipients. Patient and graft survival
      rates for right split-liver grafts were 84% and 79%, respectively. Adopting a
      liberal policy of liver splitting provides allografts of optimal quality for
      pediatric transplantation, allowing a dramatic decrease in the waiting list time.
      The in situ split-liver technique should be considered the method of choice for
      expanding the cadaveric liver donor pool.

PMID- 10915163
TI  - Combination low-dose hepatitis B immune globulin and lamivudine therapy provides
      effective prophylaxis against posttransplantation hepatitis B.
AB  - Although antiviral prophylaxis with lamivudine monotherapy appears to reduce post
      liver transplantation recurrence of hepatitis B virus (HBV) infection,
      breakthrough infections occur in at least 20% of the patients because of the
      development of drug resistance. Combined lamivudine and intravenous hepatitis B
      immune globulin (HBIG) therapy (10,000-IU doses) may reduce this risk, but its
      use is limited by cost ( approximately US $45,000/yr) and availability. We report
      the experience at liver transplant centers in Australia and New Zealand in which
      lamivudine has been used in combination with much lower doses of HBIG than used
      in conventional HBIG prophylaxis. Lamivudine, 100 mg/d, was administered to
      hepatitis B surface antigen (HBsAg)-positive candidates on listing for
      transplantation and was continued posttransplantation. HBIG, 400 or 800 IU, was
      administered intramuscularly (IM) daily for 1 week from transplantation and
      monthly thereafter. Thirty-seven HBsAg-positive patients underwent
      transplantation using this protocol. Thirty-six of these patients were HBV DNA
      positive by polymerase chain reaction (PCR) or hybridization assay. Thirty-four
      patients had chronic HBV, 2 patients had hepatitis B and C, and 1 patient had
      hepatitis B, C, and D. Five patients died within 1 month of transplantation and
      are not included in the analysis. Mean follow-up in the remaining 32 patients was
      18.4 months (range, 5 to 45 months). Treatment was well tolerated, with no
      significant adverse events. Thirty-one of 32 patients were HBsAg negative, and
      all 32 patients were HBV DNA negative by PCR at latest follow-up. The cost of
      treatment was US $967 for lamivudine and between $2,290 and $4,480/yr for IM
      HBIG. Lamivudine and low-dose HBIG treatment prevents posttransplantation
      recurrence of hepatitis B and is likely to be more cost-effective than high-dose
      HBIG regimens.

PMID- 10915164
TI  - Lamivudine after hepatitis B immune globulin is effective in preventing hepatitis
      B recurrence after liver transplantation.
AB  - The prevention of recurrent hepatitis B virus (HBV) infection after orthotopic
      liver transplantation (OLT) with hepatitis B immunoglobulin (HBIG) is expensive
      and requires indefinite parenteral administration. Lamivudine is a nucleoside
      analogue capable of inhibiting HBV replication. The aim of this study is to
      determine the efficacy of lamivudine in the prevention of recurrent HBV infection
      after a course of HBIG in patients who were hepatitis B surface antigen (HBsAg)
      positive and hepatitis Be antigen (HBeAg) negative before OLT. Patients at high
      risk for recurrent HBV infection (HBeAg positive and HBV DNA positive) were
      excluded. Thirty HBsAg-positive, HBeAg-negative patients underwent OLT from
      January 1993 to June 1997. All 30 patients were administered HBIG after OLT and,
      after 2 years, were given the option of continuing with HBIG or switching to
      lamivudine. Five patients were excluded: 3 patients were lost to follow-up and 2
      patients died of technical complications. Three patients terminated HBIG therapy
      at 8, 24, and 29 months after OLT, and reinfection with HBV occurred in 1
      patient. Six patients elected to continue HBIG therapy for life; 1 patient died
      of melanoma and the remaining 5 patients are HBsAg negative, with an average
      follow-up of 73 months. Sixteen patients were converted to lamivudine after a
      course of HBIG, and all 16 patients are HBsAg negative, with an average follow-up
      of 51 months after OLT. Five patients have been on lamivudine monotherapy for
      more than 24 months. These results suggest that lamivudine administered after a
      posttransplantation course of HBIG can effectively prevent the recurrence of HBV
      infection in patients who are HBsAg positive and HBeAg negative before OLT.

PMID- 10915165
TI  - Vaccination against hepatitis B virus in cirrhotic patients on liver transplant
      waiting list.
AB  - Patients with cirrhosis may fail to respond to anti-hepatitis B vaccine. An
      adequate response would be especially interesting when patients are on a liver
      transplant waiting list. Posttransplantation de novo hepatitis B has been well
      documented. One possible source is the grafting of organs from hepatitis B
      surface antigen (HBsAg)-negative, antibody to HBsAg (anti-HBs)-positive, antibody
      to hepatitis B core antigen-positive donors. The achievement of high titers of
      anti-HBs could be protective in this setting. We studied prospectively the
      response rate to recombinant hepatitis B vaccine (3 40-microg doses administered
      at 0, 1, and 2 months) in 62 patients with end-stage liver disease awaiting liver
      transplantation. Twenty-two patients showed antibody response (44%). A further 3
      doses were administered in 15 of 28 nonresponders and were effective in 9
      patients. Thus, the response rate reached 62% (31 of 50 patients completing 1 or
      2 vaccination schedules before liver transplantation). Classic hepatitis B
      vaccination studies of patients with cirrhosis yield lower response rates.
      Vaccination with this double-dose schedule should be considered in such patients
      before liver transplantation.

PMID- 10915166
TI  - Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in
      patients with portopulmonary hypertension undergoing liver transplantation.
AB  - In the setting of moderate to severe pulmonary artery hypertension, orthotopic
      liver transplantation (OLT) may be complicated by pulmonary hemodynamic
      instability and cardiopulmonary mortality. We retrospectively studied the
      relationship between cardiopulmonary-related mortality and initial (untreated)
      pre-OLT pulmonary hemodynamics in 43 patients with portopulmonary hypertension
      who underwent attempted OLT. Thirty-six patients were reported in 18 peer
      reviewed studies, and 7 patients underwent OLT at our institution since 1996.
      Transplantation procedure outcome, mean pulmonary artery pressure (MPAP),
      pulmonary vascular resistance (PVR), cardiac output, pulmonary capillary wedge
      pressure, and transpulmonary gradient (TPG) are summarized. Overall mortality was
      reported in 15 of 43 patients (35%). Fourteen of the 15 deaths (93%) were
      primarily related to cardiopulmonary dysfunction. Two deaths were intraoperative,
      8 deaths occurred during the transplantation hospitalization, and 4 patients died
      of cardiopulmonary deterioration posthospitalization. In 4 patients, the
      transplantation procedure could not be successfully completed. Cardiopulmonary
      mortality was associated with greater pre-OLT MPAP (49 +/- 14 v 36 +/- 7 mm Hg; P
      <.005), PVR (441 +/- 173 v 261 +/- 156 dynes.s.cm(-5); P <.005), and TPG (37 +/-
      13 v 22 +/- 10 mm Hg; P <.005). MPAP of 50 mm Hg or greater was associated with
      100% cardiopulmonary mortality. In patients with an MPAP of 35 to less than 50 mm
      Hg and PVR of 250 dynes.s.cm(-5) or greater, the mortality rate was 50%. No
      mortality was reported in patients with a pre-OLT MPAP less than 35 mm Hg or TPG
      less than 15 mm Hg. Cardiopulmonary-related mortality in OLT patients with
      portopulmonary hypertension was frequent and associated with significantly
      increased pre-OLT MPAP, PVR, and TPG compared with survivors. Treated or
      untreated, we recommend intraoperative cancellation or advise against proceeding
      to OLT for an MPAP of 50 mm Hg or greater. Patients with an MPAP of 35 to less
      than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater appear to be at high risk
      for cardiopulmonary-related mortality after OLT. A prospective study is needed to
      define optimal pretransplantation treatments and pulmonary hemodynamic criteria
      that minimize OLT mortality associated with portopulmonary hypertension.

PMID- 10915167
TI  - Perioperative mortality in patients with portopulmonary hypertension undergoing
      liver transplantation.

PMID- 10915168
TI  - Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension
      in liver transplant candidates.
AB  - Pulmonary hypertension has been associated with poor outcome after liver
      transplantation. We assessed the diagnostic accuracy of Doppler echocardiography
      in detecting significant pulmonary hypertension. Seventy-four potential liver
      transplant candidates underwent Doppler echocardiography in which the systolic
      right ventricular pressure (RVsys) was used to estimate the systolic pulmonary
      artery pressure (PAsys). Group 1 included 39 consecutive patients with RVsys
      >/=50 mm Hg who underwent elective right heart catheterization. Group 2 consisted
      of 35 patients with RVsys <50 mm Hg in whom pulmonary artery pressures were
      measured at the beginning of the transplantation procedure. The accuracy of the
      estimates by Doppler echocardiography was assessed against measurements made by
      direct catheterization. Patients in groups 1 and 2 were comparable in their
      demographic and liver disease characteristics. There was a strong correlation
      between RVsys by Doppler echocardiography and PAsys by right heart
      catheterization (r =.78, P <.01). Of the 39 patients in group 1, 29 (72%) had at
      least moderate pulmonary hypertension (mean pulmonary artery pressure [MPAP]
      >/=35 mm Hg), including 12 (30%) with severe pulmonary hypertension (MPAP >/=50
      mm Hg). Only 1 of the group 2 patients had MPAP >/=35 mm Hg. Thus, in the
      diagnosis of moderate to severe pulmonary hypertension, the sensitivity of
      echocardiography was 97% and specificity was 77%. Doppler echocardiography is an
      accurate screening test to detect moderate to severe pulmonary hypertension. We
      advise that liver transplant candidates with RVsys >/=50 mm Hg undergo right
      heart catheterization to fully characterize pulmonary hemodynamics.

PMID- 10915169
TI  - Small-diameter portacaval H-graft shunt: a paradigm shift back to surgical
      shunting in the management of variceal bleeding in patients with preserved liver
      function.
AB  - Small-diameter portacaval H-graft (SDPHG) shunts are partial portosystemic shunts
      that control variceal bleeding while preserving nutrient blood flow to the liver,
      minimizing postoperative encephalopathy and liver failure. Since July 1, 1997, we
      placed SDPHG shunts in 18 patients (age, 52.1 +/- 2.6 years; range, 35 to 72
      years) with cirrhosis (Child's class A, B, and C in 6, 10, and 2 patients,
      respectively) and refractory variceal bleeding who were not candidates for
      transplantation. Ten procedures (55.6%) were urgent or emergent. SDPHG shunts
      effectively reduced the portacaval pressure gradient (18 +/- 3 v 5 +/- 2 mm Hg; P
      <.05). Surgical times (210 +/- 11 minutes), estimated blood losses (358.3 +/-
      107.8 mL), transfusion requirements (0 transfusions in 10 patients; 55.6%; mean,
      0.9 +/- 0.3 units), and postoperative hospitalization (7.7 +/- 1.0 days) were
      excellent. Surgical mortality (30 days) was 0%. During 14. 0 +/- 1.9 months
      (range, 1.1 to 29.1 months) of follow-up, 4 patients (22.2%) died, including both
      patients with Child's class C cirrhosis. The cumulative 1-year survival rate was
      82.1% (Child's class A, B, and C, 83.3%, 90%, and 0%, respectively). Long-term
      survivors had significantly lower preoperative Child-Pugh scores compared with
      nonsurvivors (7.8 +/- 0.3 v 9.5 +/- 1.0; P <.05). Postoperative encephalopathy
      developed in 3 survivors (20%). Fifteen patients (83.3%) have not experienced
      rebleeding; shunt failure led to rebleeding in only 1 patient (5.6%). SDPHG shunt
      placement can be performed with low morbidity and surgical mortality.
      Nontransplantation candidates with Child's class A and B cirrhosis have excellent
      long-term survival with this safe, effective, and definitive treatment for
      refractory variceal bleeding.

PMID- 10915170
TI  - Pulmonary edema in patients after liver transplantation.
AB  - The aim of this study is to determine the incidence of radiological pulmonary
      edema in elective liver transplant recipients and its relationship to
      perioperative factors and postoperative course. We reviewed 102 chest radiographs
      from 34 patients who had undergone orthotopic liver transplantation (OLT). Films
      were assessed by 2 trained radiologists for evidence of pulmonary edema using a
      standardized system. Clinical and outcome data from the 34 patients were also
      recorded. There was a high incidence (47%) of postoperative radiological
      pulmonary edema that was associated with deterioration in gaseous exchange,
      elevated pulmonary artery pressure, and increased duration of ventilator
      dependence and intensive care stay. Eighteen percent of the patients developed
      edema immediately after surgery, which was associated with greater pulmonary
      artery pressure and transfusion requirements during surgery. An additional 29%
      developed edema during the next 16 to 20 hours, but there was no association with
      fluid replacement. We conclude that pulmonary edema is common after OLT and will
      influence postoperative recovery in a substantial proportion of transplant
      recipients. Excess perioperative fluid replacement is unlikely to be the sole
      mechanism of edema in these patients.

PMID- 10915171
TI  - Cerebral blood flow and oxygenation in liver transplantation for acute or chronic
      hepatic disease without venovenous bypass.
AB  - The autoregulation of cerebral blood flow (CBF) is impaired in patients with end
      stage liver disease and encephalopathy. These patients are vulnerable to sudden
      deterioration of cerebral perfusion and oxygenation during liver transplantation.
      We compared CBF and metabolism during liver transplantation without venovenous
      bypass and 24 hours postoperatively in 9 patients with acute liver failure (ALF)
      and 16 patients with chronic liver disease. A fiberoptic catheter was inserted
      cranially through the left internal jugular vein for determination of jugular
      venous oxygen saturation, cerebral oxygen extraction ratio (COER), lactate level,
      and neuron-specific enolase (NSE) level. Arterial concentrations of lactate were
      also measured. Flow velocity in the middle cerebral arteries was monitored
      bilaterally using transcranial Doppler sonography. Mean flow velocity and
      pulsatility index (PI) were regarded as indicators of intracranial pressure. Core
      body temperatures were recorded. Mild hyperventilation, perioperative
      hemofiltration, and N-acetylcysteine infusion were used according to our clinical
      practice. NSE level was greater in acute patients at the end of surgery (P <.05),
      but not 24 hours later. Lactate concentrations were greater in patients with ALF
      (P <.001) preoperatively and intraoperatively but were similar in both groups 24
      hours postoperatively. There was no difference between arterial and jugular
      venous concentrations of lactate. Changes in blood flow velocity, PI, and COER
      were parallel and without statistical significance between the groups. The
      patients' core temperature did not correlate with CBF, NSE level, or clinical
      outcome. Caval clamping was well tolerated in both patient groups.

PMID- 10915172
TI  - Endotoxins and cytokines during liver transplantation: changes in plasma levels
      and effects on clinical outcome.
AB  - Endotoxins, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL
      6 are believed to have a key role in liver transplantation. The origin and course
      of these factors is not completely known. In this prospective study of 40
      patients, we sought more understanding of the relations between these factors and
      their effects on clinical outcome by sampling at different sites. Endotoxemia was
      only present in 20% of the patients. In 75% of these patients, it was present
      during the anhepatic phase and quickly resolved after reperfusion. Endotoxemia
      was not related to a clinical adverse event. TNF-alpha was released from the
      graft after reperfusion, and initial levels after reperfusion were related to
      predonation levels in the donor. Only levels of TNF-alpha in the recipient before
      transplantation were found to be predictive of postoperative complications. We
      conclude that monitoring endotoxins and these cytokines is of very limited value
      in predicting outcome.

PMID- 10915173
TI  - Adaptation of the Mayo primary biliary cirrhosis natural history model for
      application in liver transplant candidates.
AB  - The Mayo natural history model has been used widely as a tool to estimate
      prognosis in patients with primary biliary cirrhosis (PBC), particularly liver
      transplant candidates. We present an abbreviated model in which a tabular method
      is used to approximate the risk score, which may be incorporated in the minimal
      listing criteria for liver transplant candidates. Data used in the development
      and validation of the original Mayo model were derived from 418 patients with
      well-characterized PBC. To construct an abbreviated risk score in a format
      similar to that of Child-Turcotte-Pugh score, 1 to 3 cut-off criteria were
      determined for each variable, namely age (0 point for <38, 1 for 38 to 62 and 2
      for >/=63 years), bilirubin (0 point for <1, 1 for 1 to 1.7, 2 for 1.7 to 6.4,
      and 3 for >6.4 mg/dL), albumin (0 point for >4.1, 1 for 2.8 to 4.1, and 2 for
      <2.8 g/dL), prothrombin time (1 point for normal and 2 for prolonged) and edema
      (0 point for absent and 1 for present). The intervals between these criteria were
      chosen in a way to enable a meaningful classification of patients according to
      their risk for death. This score is highly correlated with the original risk
      score (r = 0.93; P <.01). The Kaplan-Meier estimate at 1 year was 90.6% in
      patients with a score of 6. The abbreviated risk score is a convenient method to
      quickly estimate the risk score in patients with PBC. An abbreviated score of 6
      may be consistent with the current minimal listing criteria in liver transplant
      candidates.

PMID- 10915174
TI  - Cerebral edema with herniation during acetaminophen-induced fulminant hepatic
      failure.

PMID- 10915175
TI  - Acceptance of an ABO-incompatible mismatched (AB(+) to O(+)) liver allograft with
      the use of daclizumab and mycophenolate mofetil.
AB  - Liver allograft survival rates of 50% to 60% are reported in blood group A, group
      B, group O (ABO)-incompatible mismatched grafts even when aggressive
      immunosuppressive protocols, including plasmapheresis, OKT(3), cyclophosphamide,
      cyclosporine, prostaglandin E(1), and steroids, are used. A 59-year-old woman,
      blood type O(+), required emergency retransplantation posttransplantation day 2
      because of primary nonfunction of the liver allograft. A blood type AB(+)
      allograft was used. Induction immunosuppressive therapy included tacrolimus,
      mycophenolate mofetil, OKT(3) (muromonab-CD(3)), steroids, and prostaglandin
      E(1). In addition, plasmapheresis was performed daily for 9 days. OKT(3) and
      prostaglandin E(1) were also discontinued postoperative day 9. Biopsy-proven
      acute cellular rejection was diagnosed postoperative day 12 and was treated with
      double-dose OKT(3) (10 mg) for another 6 days. On the day OKT(3) was
      discontinued, daclizumab, 60 mg, was administered intravenously. This dose was
      repeated every 2 weeks for a total of 5 doses. At 1-year follow-up, the patient
      is doing very well with normal liver function. We are unaware of previous reports
      of the use of daclizumab and mycophenolate mofetil as part of an
      immunosuppressive protocol aimed to induce acceptance of ABO-incompatible
      mismatched liver allografts. Based on our experience with this case, it seems
      that mycophenolate mofetil is an adequate replacement for cyclophosphamide. We
      also believe daclizumab provided adequate protection at a critical time. Further
      experience with both these drugs is required to establish their role in ABO
      incompatible mismatched liver allografts.

PMID- 10915176
TI  - Spain model: world leaders in organ donation.

PMID- 10915177
TI  - US viewpoint.

PMID- 10915178
TI  - Let's play dominos.

PMID- 10915179
TI  - Improved survival in acute liver failure with hepatocyte therapies.

PMID- 10915181
TI  - Program abstracts for the 11th meeting of the liver intensive care group of
      europe-LICAGE

PMID- 10915182
TI  - Introduction

PMID- 10915180
TI  - Gastrointestinal transplantation: An update.
AB  - Gastrointestinal transplantation is a life-saving option for patients who have
      chronic intestinal failure and cannot tolerate total parenteral nutrition (TPN).
      Early referral is important because of the scarcity of donors and the increased
      risk of complications in debilitated recipients. One-year patient survival rates
      range from 50% to 70%. Despite the use of intense immune suppression, most
      patients experience at least 1 episode of graft rejection. More than 80% of the
      survivors are able to stop TPN and resume an unrestricted oral diet. Patients
      with functioning grafts have a good quality of life.

PMID- 10915183
TI  - Critical care issues in liver transplantation.

PMID- 10915184
TI  - Multiple organ failure during critical illness: how organ failure influences
      outcome in liver disease and liver transplantation.

PMID- 10915185
TI  - Intraoperative concerns when a liver recipient is critically ill.

PMID- 10915186
TI  - Brain edema and portal-systemic encephalopathy.

PMID- 10915187
TI  - Monitoring and treatment of intracranial hypertension.

PMID- 10915188
TI  - Bioartificial liver in the treatment of hepatic failure.

PMID- 10915189
TI  - Hepatopulmonary syndrome: recent literature (1997 to 1999) and implications for
      liver transplantation.

PMID- 10915190
TI  - Critical care issues: portopulmonary hypertension.

PMID- 10915192
TI  - Coronary artery disease and liver transplantation: the state of the art.

PMID- 10915191
TI  - Cirrhotic cardiomyopathy and liver transplantation.
AB  - Myocardial contractility in cirrhosis is impaired, particularly under stressful
      situations, in a phenomenon termed cirrhotic cardiomyopathy. Impairment of the
      cardiac beta-adrenergic receptor and its signaling function appears to be
      involved in the pathogenesis of this disorder. Additional mechanisms that may
      have a role include alterations in the physicochemical properties of the
      cardiomyocyte plasma membrane and abnormalities in circulating humoral factors,
      such as nitric oxide, carbon monoxide, and catecholamines. The widespread use of
      orthotopic liver transplantation (OLT) and its associated stresses on the
      cardiovascular system have highlighted this condition. Cardiac failure has
      emerged as an important cause of morbidity and mortality in the liver transplant
      recipient. Unfortunately, pre-OLT recognition of cirrhotic cardiomyopathy is
      suboptimal because of a lack of sensitive, noninvasive diagnostic tests.
      Similarly, the management of cirrhotic cardiomyopathy is largely empirical
      because of a paucity of existing literature. Although evidence suggests that
      cirrhotic cardiomyopathy may be reversible after OLT, the natural history of this
      condition warrants further investigation.

PMID- 10915193
TI  - Pretransplantation gastrointestinal bleeding.

PMID- 10915194
TI  - Hepatorenal syndrome.

PMID- 10915195
TI  - Coagulopathies in hepatic disease.

PMID- 10915196
TI  - Metabolism and liver transplantation: review of perioperative issues.

PMID- 10915197
TI  - Malnutrition in liver disease.

PMID- 10915198
TI  - Waste water bacterial isolates resistant to heavy metals and antibiotics.
AB  - Sewage water of Casablanca, an industrial city in Morocco, was studied for
      microorganisms resistant to heavy metals. Isolates were purified and collected on
      agar slants to be screened for resistance to heavy metals, including mercury in
      vitro. The strains that showed high resistance to heavy metals were also studied
      for their resistance to antibiotics and aromatic hydrocarbons. Results indicated
      that the strains most resistant to all tested products belonged to Ps.
      fluorescens, Ps. aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, and
      Staphylococcus sp. These strains exhibit high minimal inhibitory concentrations
      for heavy metals such as cadmium (2 mm) or mercury (1.2 mm). Growth of Ps.
      fluorescens and Klebsiella pneumoniae in the presence of heavy metals was also
      determined, and the growth curves indicated that mercury, copper, and zinc
      present a slight inhibitory action, while cadmium and silver could have a potent
      inhibitory action on growth compared with the controls. These studies also
      investigated growth in media containing aromatic compounds as the sole source of
      carbon. The results demonstrate that these strains could be good candidates for
      remediation of some heavy metals and aromatic compounds in heavily polluted
      sites.

PMID- 10915199
TI  - Formation and stability of the bacteriophage lambda replication complexes in UV
      irradiated Escherichia coli.
AB  - Bacteriophage lambda replication complex, containing the phage-encoded O
      initiator protein protected from proteases by other elements of this complex, is
      a stable structure that can be inherited by one of the two daughter lambda DNA
      copies after a replication round in Escherichia coli. In normal growth conditions
      in bacteria bearing a plasmid derived from bacteriophage lambda, such a complex
      may be stable for many cell generations. However, it was found that this stable
      structure is disassembled under certain conditions, namely, after heat shock.
      Therefore, we asked whether other environmental stresses may cause disassembly of
      the lambda replication complex. We found that UV irradiation of the host cells
      prevented formation of the stable lambda replication complex (though not
      preventing phage replication), while the same UV doses did not affect the
      stability of the replication complex assembled prior to the irradiation. These
      results indicate that the stable lambda replication complex, although sensitive
      to heat shock, is resistant to some other environmental stresses and that
      formation of at least two types of lambda replication complexes is possible. Both
      stable and unstable lambda replication complexes are functional because
      replication of lambda DNA under conditions preventing formation of the stable
      complex proceeds efficiently.

PMID- 10915201
TI  - Accumulation of a natural substrate of laccase in gills of Pleurotus florida
      during sporulation.
AB  - During sporulation, laccase activity of Pleurotus florida decreased to a minimum
      level in spite of increase in the number of isozymes. An endogenous laccase
      substrate was detected especially in the gill structure of the sporophore, which
      competitively inhibited oxidation of guaiacol by the enzyme during in vitro
      assay. Appearance of the laccase substrate in the gill structure may be linked
      with the sporulation phenomenon.

PMID- 10915200
TI  - Current status of Helicobacter contamination of laboratory mice, rats, gerbils,
      and house musk shrews in Japan.
AB  - The current status of Helicobacter contamination of laboratory mice, rats,
      gerbils, and house musk shrews from 47, 10, 4, and 3 colonies, respectively, in
      Japan was studied. Helicobacter was detected by reverse transcription (RT)-nested
      polymerase chain reaction (PCR) with Helicobacter genus-specific primers by using
      feces obtained from the animals. H. hepaticus, H. muridarum, H. bilis, H.
      rodentium, "Flexispira rappini", and "H. suncus" were identified with species
      specific primers. Other species of Helicobacter were identified by sequencing of
      PCR products amplified with genus-specific primers. For mice, H. hepaticus, H.
      bilis, H. rodentium including H. rodentium-like organism, "H. typhlonicus"-like
      organism, and H. westmeadii-like organism were detected from 12 (25.5%), 1
      (2.1%), 18 (38.3%), 1 (2.1%), and 1 (2.1%) colonies, respectively. Forty-seven
      (5.7%) mice from six (12.8%) colonies were contaminated with both H. hepaticus
      and H. rodentium. H. rodentium was detected in rats from three (30.0%) colonies.
      In gerbils, H. hepaticus was detected in three (75.0%) colonies, but other
      species of Helicobacter were not detected. In house musk shrews, "H. suncus" was
      detected in animals from two (66.7%) colonies. Visible lesions in the liver,
      which showed multiple pale to white foci, were observed in 6/42, 5/174, and 1/21
      mice infected with H. hepaticus, H. rodentium, and H. hepaticus/H. rodentium,
      respectively, and 1/14 gerbils infected with H. hepaticus. The results suggest
      the prevalence of these species of Helicobacter in mice, rats, gerbils, and house
      musk shrews in Japan.

PMID- 10915202
TI  - Expression of the rfa, LPS biosynthesis promoter in Salmonella typhimurium during
      invasion of intestinal epithelial cells.
AB  - Salmonella regulates transcription of many of its genes in response to
      environmental conditions encountered inside or outside the eukaryotic cells it
      infects. In this paper, we examined Salmonella typhimurium gene expression within
      epithelial cells, by using bacterial luciferase as a reporter. We focused on gene
      expression controlled by Salmonella rfa promoter, using lac promoter as a
      control. We observed down regulation for both promoters during the initial 2 h of
      invasion. The decreased levels of luciferase activity appeared to be due to
      metabolic changes, since we observed similar results with tissue culture medium
      alone. Gene expression stabilized to a new steady state for the Salmonella rfa
      promoter, while a lac promoter activity steadily decreased. Bacterial luciferase
      activity was a good indicator of intracellular numbers and allowed us to detect
      as few as 1000 bacterial cells/infected monolayer. Both promoters were not
      dependent on host protein synthesis for expression.

PMID- 10915203
TI  - Comparison of low-molecular-weight heat stress proteins encoded on plasmids in
      different strains of Streptococcus thermophilus.
AB  - Streptococcus thermophilus is used extensively for industrial fermentation of
      dairy products. Some strains of S. thermophilus are known to carry plasmids, and
      many of these plasmids are suspected of encoding low-molecular-weight heat stress
      proteins (Hsps) that may aid in survival under stressful conditions. In order to
      confirm the presence and examine the similarity of these low-molecular-weight
      Hsps, genes were identified and sequenced encoding Hsps on plasmids pER16 (4.5
      kb), pER35 (10 kb), and pER36 (3.7 kb) from three different strains of S.
      thermophilus. The plasmid replication proteins were also sequenced to examine
      their relatedness. Amino acid sequence comparisons of the Hsps and of the
      replication proteins revealed a high degree of identity suggesting a common
      origin. Heat stress proteins enhance the viability of bacteria in extreme
      environments, and the presence of an Hsp encoded on a plasmid may enhance
      survival of S. thermophilus under harsh production conditions.

PMID- 10915205
TI  - Hyper-production of insecticidal crystal protein (delta-endotoxin) by Bacillus
      thuringiensis var. israelensis is not related to sporulation-specific biochemical
      functions.
AB  - Hypertoxic mutant strains of Bacillus thuringiensis var. israelensis were
      isolated by mutagenesis of the parent strain. The correlation, if any, between
      hyper-production of insecticidal crystal protein (delta-endotoxin) by hypertoxic
      mutant strains of Bacillus thuringiensis var. israelensis and sporulation
      specific biochemical functions was studied. No increase in sporulation-specific
      biochemical markers was observed in the hypertoxic mutant strains. Asporogenous
      mutants of hypertoxic mutant strains blocked at different stages of sporulation
      were isolated, and larvicidal activity was studied. The hypertoxic parent strains
      and the sporulation-deficient, hypertoxic mutant strains showed almost identical
      larvicidal activity. Therefore, the increased production of toxin is not related
      to sporulation-specific biochemical changes.

PMID- 10915204
TI  - Deoxyribonuclease activity in Selenomonas ruminantium, Streptococcus bovis, and
      Bacteroides ovatus.
AB  - Six Selenomonas ruminantium strains (132c, JW13, SRK1, 179f, 5521c1, and 5934e),
      Streptococcus bovis JB1, and Bacteroides ovatus V975 were examined for nuclease
      activity as well as the ability to utilize nucleic acids, ribose, and 2
      deoxyribose. Nuclease activity was detected in sonicated cells and culture
      supernatants for all bacteria except S. ruminantium JW13 and 179f sonicated
      cells. S. ruminantium strains were able to utilize several deoxyribonucleosides,
      while S. bovis JB1 and B. ovatus V975 showed little or no growth on all
      deoxyribonucleosides. When S. ruminantium strains 5934e, 132c, JW13, and SRK1
      were incubated in medium that contained 15 mm ribose, the major end products were
      acetate, propionate, and lactate. S. ruminantium 5521c1 and S. bovis JB1 did not
      grow on ribose, and none of the S. ruminantium strains or S. bovis JB1 grew on 15
      mm 2-deoxyribose. In contrast, B. ovatus V975 was able to grow on ribose and 2
      deoxyribose. In conclusion, all S. ruminantium strains, S. bovis JB1, and B.
      ovatus V975 had nuclease activity. However, not all bacteria were able to utilize
      deoxyribonucleosides, ribose, or 2-deoxyribose.

PMID- 10915206
TI  - Effect of a new variety of Apis mellifera propolis on mutans Streptococci.
AB  - The effects of a new variety of propolis, from Northeastern Brazil (BA), on
      growth of mutans streptococci, cell adherence, and water-insoluble glucan (WIG)
      synthesis were evaluated. Propolis from Southeastern (MG) and Southern (RS)
      Brazil were also tested as an extension of our previous work. Ethanolic extracts
      of propolis (EEP) were prepared and analyzed by reversed-phase HPLC. For the
      antibacterial activity assays, minimum inhibitory concentrations (MIC) and
      minimum bactericidal concentrations (MBC) of EEPs against Streptococcus mutans,
      S. sobrinus, and S. cricetus were determined. Cell adherence of S. mutans and S.
      sobrinus to a glass surface was measured spectrophotometrically at 550 nm. WIG
      synthesized from sucrose by glucosyltransferase (Gtf) was extracted and
      quantified by the phenol-sulfuric method. The HPLC profile of the new variety of
      propolis was entirely different from Southeastern and Southern propolis. Neither
      flavonoid aglycones nor p-coumaric acid were detected in EEP BA. All EEPs
      demonstrated biological activities against mutans streptococci; EEP BA showed the
      highest potency in all in vitro parameters evaluated in this study. The ranges of
      MIC values were 50 (EEP BA)-400 microg/ml (MG), for S. mutans; and 25 (BA)-400
      microg/ml (MG), for S. sobrinus and S. cricetus. The bactericidal concentration
      of EEPs was four to eight times the MIC values. The adherence of S. mutans and S.
      sobrinus cells and WIG synthesis were markedly inhibited by EEPs, demonstrating
      significant inhibition at all concentrations compared with the control (80%
      ethanol) (p<0.05). EEP BA showed 80% inhibition of cell adherence and WIG
      synthesis at concentrations as low as 12.5 and 7.8 microg/ml, respectively. The
      results show that the new variety of propolis was exceptionally effective in all
      in vitro parameters tested against mutans streptococci; biological effects of
      propolis are likely not to be due solely to flavonoids and (hydroxy)cinnamic acid
      derivatives.

PMID- 10915207
TI  - Determinative value of a portion of the nifH sequence for the genera Nostoc and
      Anabaena (cyanobacteria).
AB  - The taxonomic positions of Nostoc and Anabaena strains are currently disputed. We
      selected three Nostoc and Anabaena strains, using the classic criteria of
      morphology and life cycle. DNA sequences of a part of the nifH gene were
      determined from these strains and aligned with homologous sequences from 10 other
      Nostoc/Anabaena strains in the public databases. Phylogenetic reconstructions
      were carried out to test the consistency of the taxonomic placement of these
      strains. The phylogenetic trees do not separate these strains into distinct
      groups. Our results are in agreement with other molecular-based phylogenies that
      also fail to differentiate the Nostoc-Anabaena groups. The data suggest that the
      currently recognized genera Nostoc and Anabaena may in fact belong within a
      single, broadly defined genus.

PMID- 10915208
TI  - Susceptibility to heavy metals and cadmium accumulation in aerobic and anaerobic
      thermophilic microorganisms isolated from deep-sea hydrothermal vents.
AB  - Thirty thermophilic strains isolated from heavy metal-rich hydrothermal vent
      sites at Lau Basin were tested for their susceptibility to cadmium, zinc, cobalt,
      and nickel. The 14 aerobic spore formers belonging to the genus Bacillus, 6
      anaerobic fermenters from the order Thermotogales, and 10 anaerobic sulfur
      reducers from the order Thermococcales could be clearly distinguished according
      to their metal susceptibilities. The Thermococcales were found to exhibit the
      highest resistance to cadmium and zinc, whereas Thermotogales were highly
      sensitive to these metals. In contrast, the Thermotogales displayed the highest
      resistance to cobalt ions. No clear distinction could be established between the
      metal susceptibilities of these strains and seven reference organisms used for
      comparative studies. Cadmium resistance, slightly inducible in some cadmium
      resistant bacilli, was not plasmid mediated. The amount of cadmium immobilized by
      the Thermotogales was related to their level of resistance to this metal.

PMID- 10915209
TI  - Volatile organic compounds associated with microbial growth in automobile air
      conditioning systems.
AB  - Volatile organic compounds from Penicillium viridicatum and Methylobacterium
      mesophilicum growing on laboratory media and on component materials of automobile
      air conditioners were analyzed with gas chromatography and mass spectrometry. P.
      viridicatum produced compounds such as 4-methyl thiazole, terpenes and alcohols,
      whereas M. mesophilicum produced dimethyl disulfide, dimethyl trisulfide, and
      chlorophenol with growth on laboratory media. In comparison with laboratory
      media, fewer volatiles were detected from colonized foam insulation materials.
      Biofilms of M. mesophilicum on aluminum evaporator components produced mainly
      dimethyl disulfide. These biofilms, after inoculation with P. viridicatum,
      produced offensive smelling alcohols and esters such as 2-methyl propanol, 3
      penten-2-ol, and the ethyl ester of butanoic acid. The moisture and substrates
      innate to the automobile air conditioning systems provided an environment
      suitable for microbial biofilm development and odor production. Reduction of
      retained moisture in the air conditioning system coupled with use of less
      susceptible or antimicrobial substrates are advised for remediation of the
      noxious odors.

PMID- 10915210
TI  - Antibacterial carbohydrate monoesters suppressing cell growth of Streptococcus
      mutans in the presence of sucrose.
AB  - The growth-inhibitory effect of 23 carbohydrate monoesters synthesized by lipases
      and proteases were assayed to obtain antibacterial agents that suppress the cell
      growth of Streptococcus mutans. Among the carbohydrate esters synthesized,
      galactose and fructose laurates showed the highest growth-inhibitory effect,
      while the other analogs of hexose laurates showed no antibacterial activity,
      indicating that configuration of the hydroxyl group in carbohydrate moiety
      markedly affects the antibacterial activity. The cell growth of S. mutans was
      suppressed by fructose laurates even in the presence of sucrose. Thus, enzymatic
      synthesis of carbohydrate esters with different core structures has great
      potential for developing antibacterial agents applicable to food additives.

PMID- 10915211
TI  - Bacillus thuringiensis delta-endotoxin proteins show a correlation in toxicity
      and short circuit current inhibition against Helicoverpa zea.
AB  - Pesticidal activity of Bacillus thuringiensis delta-endotoxins, Cry1Aa, Cry1Ab,
      Cry1Ac, and Cry2A, was determined by using the force-feeding bioassay method to
      4(th) instar larvae of Helicoverpa zea. H. zea was susceptible to Bt toxins in
      the order Cry1Ac > Cry1Ab > Cry1Aa > Cry2A with 63.60, 89.04, 159.65, and 375.78
      ng/larvae respectively. The abilities of selected Bacillus thuringiensis toxins
      to inhibit short circuit current (I(SC)) in midgut epithelia of H. zea were also
      investigated by voltage clamp assay. The voltage-clamp studies were conducted on
      isolated midguts, measuring the inhibition of short circuit current (I(SC)) by
      activated toxin. A Cry1Aa toxin dilution of 33.3 and 500 ng/ml resulted in
      inhibition of I(SC) of -2.29 microA/min (lag time 15 min) and -4.48 microA/min
      (lag time, 2 min) respectively. The Cry1Ab dilution of 25 ng/ml inhibited I(SC)
      to -1.39 microA/min, a lag time of 14 min, and 333.3 ng/ml dilution resulted in
      decay of I(SC) -2.49 microA/min, lag time 1 min respectively. The Cry1Ac lower
      dilution 16.7 ng/ml inhibited I(SC) to -1.39 microA/min, lag time 4 min, and a
      high dilution 333.3 ng/ml decay I(SC) to -2.44 microA/min, lag time 1 min. The
      inhibition of I(SC) (-1.10 microA/min, lag time 25) at lower dilution (33.3
      ng/ml) and high dilution (500 ng/ml), decay (-2.38 microA/min, lag time 5 min),
      showed a correlation between toxin concentration and inhibitory response with
      Cry2A toxin. The lag time decreased with increasing concentration of toxin
      applied, which is additional evidence of dose response besides direct correlation
      of toxicity assays and I(SC).

PMID- 10915212
TI  - Nucleotide sequence of alpha-galactosidase MEL gene from Zygosaccharomyces
      mrakii.
AB  - The region encompassing the alpha-galactosidase MELr gene was amplified from
      Zygosaccharomyces mrakii IFO 1835(T) by inverse-PCR and then sequenced. The
      nucleotide sequence of this region revealed a single open reading frame of 1410
      bp encoding a 470 amino acid protein with a molecular weight of 51,909. The
      similarity of the deduced mature protein to other yeast alpha-galactosidases was
      63.3% to Zygosaccharomyces cidri, 71.5% to Torulaspora delbrueckii, and 70. 7
      73.9% to Saccharomyces species. The nucleotide and amino acid sequences are
      deposited in the DDBJ/EMBL/GenBank database under Accession Number AB030209.

PMID- 10915214
TI  - Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in
      human physiology and disease.
AB  - In women and men, an important proportion of estrogens and androgens are
      synthesized locally at their site of action in peripheral target tissues. This
      new field of endocrinology has been called intracrinology. In postmenopausal
      women, 100% of active sex steroids are synthesized in peripheral target tissues
      from inactive steroid precursors while, in adult men, approximately 50% of
      androgens are made locally in intracrine target tissues. The last and key step in
      the formation of all estrogens and androgens is catalyzed by members of the
      family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs) while different 17
      beta-HSDs inactivate these steroids in the same cell where synthesis takes place.
      To date, seven human 17 beta-HSDs have been cloned, sequenced and characterized.
      The 17 beta-HSDs provide each cell with the means of precisely controlling the
      intracellular concentration of each sex steroid according to local needs.

PMID- 10915215
TI  - Hormonal regulation of mRNA stability and RNA-protein interactions in the
      pituitary.
AB  - Regulating gene expression from DNA to protein is a complex multistage process
      with multiple control mechanisms. Transcriptional regulation has been considered
      the major control point of protein production in eukaryotic cells; however, there
      is growing evidence of pivotal posttranscriptional regulation for many genes.
      This has prompted extensive investigations to elucidate the mechanisms
      controlling RNA processing, mRNA nuclear export and localization, mRNA stability
      and turnover, in addition to translational rates and posttranslational events.
      The regulation of mRNA stability has emerged as a critical control step in
      determining the cellular mRNA level, with individual mRNAs displaying a wide
      range of stability that has been linked to discrete sequence elements and
      specific RNA-protein interactions. This review will focus on current knowledge of
      the determinants of mRNA stability and RNA-protein interactions in the pituitary.
      This field is rapidly expanding with the identification of regulated cis-acting
      stability-modifying elements within many mRNAs, and the cloning and
      characterization of trans-acting proteins that specifically bind to their cognate
      cis elements. We will present evidence for regulation of multiple pituitary genes
      at the level of mRNA stability and some examples of the emerging data
      characterizing RNA-protein interactions.

PMID- 10915216
TI  - Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance.
AB  - Conversion of C(19) steroids to estrogens is catalyzed by aromatase in human
      ovary, placenta and extraglandular tissues such as adipose tissue, skin and the
      brain. Aromatase activity is not detectable in normal endometrium. In contrast,
      aromatase is expressed aberrantly in endometriosis and is stimulated by
      prostaglandin E(2) (PGE(2)).( )This results in local production of estrogen,
      which induces PGE(2) formation and establishes a positive feedback cycle. Another
      abnormality in endometriosis, i.e. deficient hydroxysteroid dehydrogenase (17beta
      HSD) type 2 expression, impairs the inactivation of estradiol to estrone. These
      molecular aberrations collectively favor accumulation of increasing quantities of
      estradiol and PGE(2 )in endometriosis. The clinical relevance of these findings
      was exemplified by the successful treatment of an unusually aggressive case of
      postmenopausal endometriosis using an aromatase inhibitor.

PMID- 10915217
TI  - mRNA expression profiles for corticotrophin-releasing factor (CRF), urocortin,
      CRF receptors and CRF-binding protein in peripheral rat tissues.
AB  - The expression and activities of corticotrophin-releasing factor (CRF), urocortin
      (UCN), the CRF-binding protein (CRF-BP) and CRF receptors in rat brain have been
      well documented; however, information regarding their peripheral distributions
      remains incomplete. Given the multiple immunomodulatory effects of peripherally
      administered CRF and UCN and the high levels of CRF receptor type 2 (CRF-R2) mRNA
      and protein expressed in the heart, the lymphoid organs and heart have become
      targets for some of the latest CRF-related research. Here we demonstrate the
      presence of UCN mRNA in both the rat spleen and human Jurkat T-lymphoma cells
      using 3'-RACE (rapid amplication of cDNA ends) PCR. Following on from these
      initial results, we used semi-quantitative RT-PCR to carry out a comprehensive
      study assessing the relative amounts of CRF, UCN, CRF-R1, CRF-R2 and CRF-BP mRNAs
      in the brain, thymus, spleen and heart of normal, untreated rats. The rank orders
      of mRNA abundance in each of the tissue types were as follows: for CRF,
      brain>>thymus=spleen=heart; for UCN, heart>/=brain>thymus>spleen; for CRFR1,
      brain>>thymus>spleen (absent in heart); for CRF-R2, brain=heart>thymus>spleen;
      and CRF-BP was only detectable in the brain. We have provided evidence for the
      existence of CRF, UCN, CRF-R1 and CRF-R2 expression in resting immune cells, with
      UCN expression being particularly predominant in the rat thymus and human Jurkat
      cells. Additionally, the high levels of UCN mRNA detected in heart corresponded
      to the high expression of CRF-R2 mRNA, suggesting an important role for UCN/CRF
      R2 coupling in this tissue.

PMID- 10915218
TI  - Inhibitory effect of retinoic acid on the development of immature porcine
      granulosa cells to mature cells.
AB  - The present study investigated the effect of retinoic acid (RA) on the
      differentiation of granulosa cells prepared from porcine ovaries. The granulosa
      cells were precultured for 15 h, then cultured for 48 h with FSH and further
      treated for 24 h with LH in order to induce their transformation into luteal
      cells. After the cells had been exposed to 1 microM retinoids (RA, retinal and
      retinol) for 87 h, analysis of the LH receptor mRNA expression, an indicator of
      granulosa cell differentiation, was carried out by using semiquantitative RT-PCR.
      The results showed that there was a decrease in LH receptor mRNA levels, and that
      RA had a more potent effect on these levels than the other two retinoids. When
      cells were exposed to RA in the immature stage (before the addition of FSH) or
      the early stage of development (0-24 h after the addition of FSH), expression of
      LH receptor mRNA was greatly diminished. When the immature cells were cultured
      for 15 h with RA, then washed and cultured for 48 h with FSH and for 24 h with
      LH, the expression of LH receptor mRNA was not reversed. In the differentiated
      cells (24 h after the addition of FSH), however, RA no longer had any inhibitory
      effect. When the immature cells were exposed to RA, FSH-induced expression of c
      fos mRNA was markedly decreased. In contrast, expression of c-jun and activating
      transcription factor-4 mRNAs remained constant. However, the expression of c-fos
      mRNA was not decreased by forskolin. The results indicate that RA is a potent
      inhibitor in the immature stage of porcine granulosa cell differentiation,
      probably through decreased expression of FSH receptor, but that RA does not
      inhibit differentiation in the mature stage of the cells.

PMID- 10915219
TI  - Somatostatin receptor gene expression and inhibitory effects of octreotide on
      primary cultures of orbital fibroblasts from Graves' ophthalmopathy.
AB  - To explore the mechanism underlying the effects of the somatostatin (SST)
      analogue octreotide in Graves' ophthalmopathy (GO), we investigated the
      expression of SST and of SST receptor (sst(1-5)) genes in primary cultures of
      fibroblasts established from retroorbital tissue of GO patients and of control
      subjects. We determined also SST specific binding sites by competitive binding of
      [(125)ITyr(11)]SST-14 and the effect of octreotide on cell growth, cAMP
      accumulation, Bcl-2 intracellular levels and apoptosis in GO fibroblast primary
      cultures. All primary cultures expressed the SST gene transcript and one or more
      ssts that have a high affinity for the two analogues (class 1 sst. The sst(2)
      transcript was found in nine, sst(3) in five and sst(5) in eight out of ten GO
      cell cultures. Sst(2) was detected in all six, and sst(3) in four out of the six
      control cell cultures. Sst(4) was absent from all samples, and sst(1) was found
      only in six out of the ten GO samples. SST-14 and octreotide inhibited the
      binding of [(125)I-Tyr(11)]SST-14 with a half-maximal inhibition of binding
      (IC(50)) of 0.80+/-0.37 and 33. 7+/- 33.1 nmol/l respectively in GO cell
      cultures, and with an IC(50) of 0.9 and 1.5 nmol/l in control cultures.
      Octreotide (10(-6) and 10(-7) M) significantly decreased (P<0.001) forskolin
      induced but not basal cAMP accumulation; at both doses for 72 h it inhibited cell
      growth (20 and 55% respectively), and induced apoptosis (20 and 40%), and
      abolished Bcl-2 protein in cell lysates. In conclusion, SST and sst transcripts
      are expressed and functional in cultured retroorbital fibroblasts. The presence
      of class 1 sst in GO tissue and the inhibition exerted by octreotide on
      retroorbital cell growth and activity in vitro may account for the effects of SST
      analogue administration in vivo in GO.

PMID- 10915220
TI  - Parathyroid hormone induces rat interstitial collagenase mRNA through Ets-1
      facilitated by cyclic AMP response element-binding protein and Ca(2+)/calmodulin
      dependent protein kinase II in osteoblastic cells.
AB  - Parathyroid hormone (PTH), a powerful bone-resorbing agent, is capable of
      stimulating interstitial collagenase (MMP-13) mRNA production in osteoblastic
      cells. In this study, a PEA3 consensus binding sequence (-80; AGGAAGT) in
      addition to a 'TRE-like' sequence (-89; CGACTCA) in the 5' upstream regulatory
      region of the rat MMP-13 gene were examined. In response to PTH, there was a time
      dependent increase in binding of nuclear factors to an oligonucleotide containing
      the PEA3 region (-95 to -71). This increase in binding was first observed at 0.5
      h, peaked at 4 h (7. 6-fold) then returned to basal levels by 24 h. Mutagenesis
      of the PEA3 site in a chloramphenicol acetyl transferase (CAT) construct
      containing 5' upstream regulatory sequence of the rat MMP-13 gene significantly
      decreased activation by PTH. PTH-mediated binding of nuclear factors to an
      oligonucleotide containing the mutant PEA3 sequence was decreased as compared
      with the wild type. Mutation or deletion of the TRE-like sequence affected basal
      as well as PTH-mediated induction of corresponding CAT constructs. Treatment with
      KN93, a Ca(2+)/calmodulin-dependent protein kinase II specific inhibitor, greatly
      reduced the amount of protein binding to the PEA3 region in response to PTH which
      correlated to a notable decrease in the amount of MMP-13 mRNA produced in
      response to PTH. Antibodies against Ets-1, cyclic AMP response element (CREB)
      binding protein (CBP) and CREB were capable of supershifting proteins binding to
      the oligonucleotide containing the PEA3 region. These data suggest a possible co
      operative interaction of factors binding to the PEA3 and TRE-like sequences and
      provide the first indication of a role for a calcium-mediated pathway in the PTH
      induction of MMP-13 mRNA in osteoblastic cells.

PMID- 10915221
TI  - Effect of the androgen receptor CAG repeat polymorphism on transcriptional
      activity: specificity in prostate and non-prostate cell lines.
AB  - The action of androgens is essential for the development of benign prostatic
      hyperplasia and carcinoma of the prostate. The androgen receptor is a ligand
      dependent nuclear transcription factor. The transcriptional activation domain of
      the androgen receptor gene contains a polymorphic CAG repeat sequence. A shorter
      CAG repeat sequence within the normal range has been reported to be associated
      with increased risk of prostate cancer and symptomatic benign prostatic
      hyperplasia. Here, we examine the in vitro transcriptional activity of the
      androgen receptor (AR) with different numbers of CAG repeats within the normal
      range in a number of different cell lines of prostatic (LNCaP, PC3) and non
      prostatic (COS-1, MCF7) origin. We utilize a luciferase reporter driven by the
      rat probasin promoter (-286/+28) containing two androgen receptor binding sites.
      Transcriptional activation of the androgen responsive reporter was observed to be
      greater with the AR containing 15 vs 31 CAG repeats in COS-1 cells (123.2+/-16.6
      vs 78.2+/-10.9, P value 0.01) and the well differentiated prostate cancer cell
      line LNCaP (103.4+/-17.7 vs 81.4+/-7.7, P value 0.045). No difference was
      observed in the poorly differentiated prostate cancer cell line, PC3 (106.9+/
      21.9 vs 109. 6+/-21.4, P>0.5) or the breast cancer cell line MCF7 (120.4+/-39.4
      vs 103.1+/-23.1, P value >0.5). Dose-response experiments with varying quantities
      of ligand (0.01, 0.1, 1 and 10 nM dihydrotestosterone) or AR cDNA did not
      demonstrate significant differences in transactivation of the androgen responsive
      reporter in PC3 cells by the different AR constructs. This suggests that the lack
      of influence of CAG number in this prostatic cell line is not related to dose of
      ligand or quantity of androgen receptor. Western immunoblot analysis of androgen
      receptor protein in transiently transfected COS-1 cells did not demonstrate a
      difference in the expression of the androgen receptor protein with different
      numbers of CAG repeats following incubation in the presence or absence of
      androgen. Gel shift assay did not demonstrate increased DNA binding by androgen
      receptor with a shorter CAG repeat sequence. These experiments using a relatively
      androgen- and prostate-specific reporter provide evidence for an inverse
      relationship between androgen receptor transcriptional activity and the number of
      CAG repeats in the transcriptional activation domain. The effect of CAG repeat
      number was cell specific suggesting the involvement of accessory factors
      expressed differentially between different cell lines.

PMID- 10915222
TI  - Functional role of a novel cis-acting element (GAGA box) in human type-1
      angiotensin II receptor gene transcription.
AB  - GH/growth factors have been shown to increase angiotensin type 1 receptor
      expression. In the present study we determined the cis-acting regulatory region
      controlling GH-induced transcription of the human type-1 angiotensin receptor
      (hAT(1)). In human proximal tubule cells transfected with a chloramphenicol
      acetyl transferase (CAT) reporter plasmid under the control of the hAT(1)
      promoter, GH induced CAT activity. Serial deletions of the hAT(1) promoter region
      indicated that an area between -314 bp and -70 bp upstream of the 5'-end of the
      cDNA sequence was essential for this activation to occur. Although sequence
      analysis identified putative multiple nuclear protein binding sites in this
      region, we determined that a 12 bp sequence (5'-GAGAGGGAGGAG-3', GAGA box)
      located between -161 bp and -149 bp was important for GH-mediated activation.
      Using mobility shift assays we demonstrated increased DNA binding activity to the
      labeled GAGA box in nuclear extracts treated with GH, suggesting this sequence is
      a GH response element. Southwestern analysis identified an 18 kDa GAGA box
      binding protein (GAGA-BP). GH-induced activity of the GAGA-BP occurred within 2.5
      min and reached a maximum at 5 min. Activation did not require de novo protein
      synthesis. Removal of the GAGA box abolished GH-induced transcription as well as
      basal transcription of the hAT(1) gene. Additional studies demonstrated that
      epidermal growth factor, platelet-derived growth factor and insulin activate the
      GAGA-BP, suggesting these growth factors can also regulate the transcription of
      the hAT(1) gene through the GAGA box. Our data show that the GAGA-BP acts as a
      trans-acting factor binding to the cis-acting regulatory element in the hAT(1)
      promoter, which is necessary for the basal and growth factor(s)-mediated
      transcriptional activation of the hAT(1) gene.

PMID- 10915223
TI  - Octreotide inhibits the enterochromaffin-like cell but not peroxisome
      proliferator-induced hypergastrinemia.
AB  - The peroxisome proliferator ciprofibrate induces hypergastrinemia and as a
      consequence, enterochromaffin-like (ECL) cell hyperplasia. The mechanism for the
      gastrin cell stimulation is unknown. The somatostatin analog octreotide LAR (long
      acting release) was used to see if the stimulating effects of ciprofibrate could
      be attenuated. Female Fischer rats were dosed with ciprofibrate (50 mg/kg body
      weight per day) alone or combined with octreotide LAR (10 mg/30 days) for 60
      days. Plasma gastrin and histamine, gastric endocrine cell densities and mRNA
      abundances were measured. Ciprofibrate increased gastrin mRNA abundance (P<0.05),
      gastrin cell number (P<0. 001) and cell area (P<0.01), and induced
      hypergastrinemia (P<0.001). These rats had profound ECL cell hyperplasia,
      confirmed by an increase in chromogranin A (CgA) and histidine decarboxylase
      (HDC) mRNA, density of neuroendocrine and ECL cells and plasma histamine levels
      (all P<0.001). Octreotide LAR did not affect ciprofibrate stimulation of gastrin
      cells, but all parameters of ECL cell hyperplasia were reduced (P<0.001).
      Octreotide LAR also significantly inhibited basal ECL cell function and growth.
      Ciprofibrate stimulates gastrin cell activity by a mechanism unaffected by
      octreotide, but octreotide does inhibit basal and gastrin-stimulated ECL cell
      function and growth.

PMID- 10915224
TI  - Prohormone convertase and autocrine growth factor mRNAs are coexpressed in small
      cell lung carcinoma.
AB  - A hallmark of small cell lung carcinoma (SCLC) is the expression of autocrine
      growth factors such as neurotensin and gastrin-releasing peptide, which bind to
      cellular receptors and stimulate cell division. The biological activity of
      autocrine growth factors requires the concurrent expression of prohormone
      convertases that cleave the growth factors to their active form, suggesting the
      expression of these genes is linked in SCLCs. RNase protection assays were used
      to detect the expression of autocrine growth factor and prohormone convertase
      mRNAs in a panel of lung cancer cell lines. These mRNAs are coexpressed in SCLC
      and lung carcinoid cell lines, but not in normal lung epithelium or in non-small
      cell lung cancers. These findings, together with earlier results from our
      laboratory, suggest the expression of prohormone convertases has an important
      role in the development and maintenance of the SCLC phenotype and that autocrine
      growth factor and prohormone convertase genes respond to a common transcriptional
      activator in SCLC.

PMID- 10915225
TI  - Effects of ketoacidosis on rat apolipoprotein A1 gene expression: a link with
      acidosis but not with ketones.
AB  - To determine if ketoacidosis contributes to reduced apolipoprotein A1 (apoA1)
      expression in insulin-deficient diabetic rats, we examined the regulation of
      apoA1 gene expression in response to changes in ambient pH or ketone body
      concentrations. Hepatic apoAI mRNA levels were reduced 42% in diabetic rats
      relative to nondiabetic controls (means+/-s.d.; 321.8+/-43.7 vs 438.7+/-58.8
      arbitrary units; P<0.03). Neither endogenous apoA1 mRNA nor transcriptional
      activity of the rat apoA1 gene promoter (from -474 to -7) were altered by sodium
      butyrate or isobutyramide (0.3 mM to 10 mM) in Hep G2 or Caco-2 cells. Rat
      hepatic and intestinal apoA1 mRNA levels, and plasma apoA1 concentration, were
      not altered 24 h after isobutyramide administration (500 mg/kg by gavage). When
      the effect of altering ambient pH within a wide range commonly encountered in
      vivo was studied, acidosis (pH 6.7), relative to alkalosis (pH 7.9), decreased
      apoAI mRNA levels relative to glyceraldehyde-3-phosphate dehydrogenase mRNA by
      47% in Hep G2 cells (P<0.025) and by 24% in Caco-2 cells (P<0.017). Acidosis did
      not alter cytomegalo virus (CMV)-beta-galactosidase activity, or the activity of
      the simian virus (SV40) early-region promoter, in either cell line transfected
      with the respective constructs. The lowering of ambient pH was associated with a
      graded reduction in apoAI promoter activity. At pH 6.7, apoAI promoter activity
      was reduced by 75% compared with promoter activity at pH 7.9. These observations
      indicate that acidosis, but not ketosis, contributes to the reduction in apoA1
      expression during diabetic ketoacidosis by down-regulating apoAI promoter
      activity.

PMID- 10915226
TI  - Cuff width and accuracy of measurement of blood pressure.

PMID- 10915227
TI  - Optimizing cuff width for noninvasive measurement of blood pressure.
AB  - BACKGROUND: It is well established that indirect measurements of blood pressure
      made with a standard 13cm-wide cuff are erroneously high for large arms and low
      for small arms. To correct for this error, the American Heart Association
      recommends adjusting cuff width to 40% of the arm's circumference. OBJECTIVE: To
      test the validity of this method of correction. DESIGN: This study was a
      prospective, nonblinded, paired Student's t-test analysis. METHODS: Blood
      pressures in 50 subjects were measured directly by using a radial artery line and
      indirectly by the Korotkov method. For each subject multiple indirect
      measurements of blood pressure were made with the cuff width:arm circumference
      ratio varied from 30-55% in 5% increments. Error was defined as indirect blood
      pressure minus direct blood pressure. RESULTS: A ratio of 40% resulted in
      overestimation of blood pressure for most arms and with particularly high errors
      for small arms. The ratio producing zero mean error for the pooled study group
      was 46.4+/-0.7% (mean+/-SEM). Using this ratio of 46.4%, the error varied
      inversely with arm circumference (P<0.02), resulting in overestimation of
      systolic blood pressure for small arms and underestimation of systolic blood
      pressure for large arms. This error is comparable in magnitude, but opposite in
      sign, to that which occurs with a standard 13cm-wide cuff for all arms. The
      optimum ratio was found to be closely approximated by the relationship, cuff
      width=9.34 log(10) arm circumference. Using this relationship, error in systolic
      blood pressure was insensitive to arm circumference (r=0.04, P>0.05) and near
      zero. CONCLUSION: The optimum cuff width for the indirect measurement of blood
      pressure is not directly proportional to arm circumference, but is proportional
      to the logarithm of the arm's circumference.

PMID- 10915228
TI  - Validation of the CAS Medical Systems, inc. OscilloMitt, hand-blood-pressure
      cuff.
AB  - BACKGROUND: There are technical difficulties in accurately measuring blood
      pressure of individuals with varying arm and body sizes. OBJECTIVE: To perform
      validation testing with 109 children of a novel cuff that occludes the palm
      rather than the upper arm. METHODS: This cuff, the OscilloMitt made by CAS
      Medical Systems, Inc. , was used in conjunction with a commercially available
      monitor. Readings of blood pressure taken by trained auscultatory observers were
      compared with those of the OscilloMitt monitor. The mean difference in systolic
      blood pressure was 1.13mmHg and the mean difference in diastolic blood pressure
      was 0.94mmHg. The OscilloMitt was tolerated very well, especially by the young
      children (those aged <5years). CONCLUSION: The OscilloMitt is accurate and its
      use should be preferable to traditional upper-arm placement of cuffs for
      assessing many specific groups of patients. We recommend its use for persons aged
      2 years and more.

PMID- 10915229
TI  - Arterial hypertension in children and adolescents after surgical repair of aortic
      coarctation defined by ambulatory blood pressure monitoring.
AB  - BACKGROUND: Despite early operation, persistent and late systolic hypertension
      are common among children and adolescents after surgical repair of aortic
      coarctation and can contribute to early cardiovascular morbidity. METHODS:
      Ambulatory blood pressure monitoring was performed for 78 patients (aged 3.6-22.8
      years, 41 male) after successful surgical repair of aortic coarctation (median
      duration of follow-up 6.5 years, range 0.7-20.1 years). Hypertension was defined
      as mean systolic blood pressure exceeding the 95th percentile for sex and height.
      RESULTS: Twenty-three patients (29%) exhibited systolic hypertension during
      daytime. Hypertensive patients had been older at the time of operation than had
      normotensive patients (5.4+/-5.0 versus 2.4+/-3.1 years, P<0.01). Prevalence of
      hypertension was 21% among patients who had undergone surgery during the first
      year of life and 38% among patients who had been operated upon later. Decline in
      blood pressure during night was similar for all patients (systolic 11+/-5% and
      diastolic 19+/-8%). Systolic hypertension during night-time was found in 24% of
      patients who were normotensive during day. Diastolic hypertension was rare.
      Follow-up measurements were performed for 41 patients after 2.3+/-1. 3 years, and
      most normotensive patients remained normotensive during this time. CONCLUSIONS:
      Ambulatory blood pressure monitoring allows one to estimate nocturnal
      hypertension in children and adolescents after surgical repair of aortic
      coarctation which is common also among normotensive patients during daytime.

PMID- 10915230
TI  - Ambulatory blood pressure variation in normotensive subjects in relation to the
      sitting or standing position.
AB  - OBJECTIVE: To evaluate the physiological variations in arterial blood pressure in
      normotensive subjects during activity and in relation to the sitting or lying
      position. METHODS: The subjects were 30 healthy volunteers who were normotensive
      and receiving no treatment. Blood pressure was measured using the validated
      monitor Diasys Integra (NOVACOR SA, Rueil-Malmaison, France) with an integral
      position sensor. Blood pressure was recorded every 15min over a 24h period,
      additional measurements being made in the first, third and sixth minutes after
      standing up. RESULTS: During the active period (1000-2000h), 53% of the measures
      were made in the standing position. Over this period, the values of systolic
      blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were
      significantly elevated in the standing position in comparison to the sitting
      position. The difference was of the order of 5mmHg for the SBP, 3.5mmHg for the
      DBP and 9beats/min for the heart rate. The SBP, DBP and heart rate measured in
      the first, third and sixth minutes after standing up were not significantly
      different. CONCLUSION: When measuring the blood pressure and heart rate in
      ambulatory patients, it seems justified to evaluate the patient's position during
      monitoring in order to achieve a better reproducibility and also to uncover any
      problems of blood pressure control with positional change, as could exist in
      patients with autonomic dysfunction. This might also aid in evaluating
      antihypertensive treatment and also any deleterious hypotensive effects.

PMID- 10915231
TI  - A cross-over evaluation of different methods and devices to measure blood
      pressure in type 1 diabetic patients with nephropathy.
AB  - BACKGROUND: In type 1 diabetic patients with nephropathy, tight blood pressure
      control has been shown to prevent the progression of the disease. Up until now,
      self-monitoring, ambulatory and office blood pressure values have not been
      compared in these patients. Thus, we have evaluated blood pressure values
      obtained in the office by a physician and at home by self-monitoring with those
      measured under ambulatory conditions in these patients. Additionally, for blood
      pressure self-monitoring, three different devices (the sphygmomanometer, upper
      arm oscillometer and wrist oscillometer) were compared. METHODS: Twenty-one
      treated hypertensive type 1 diabetic patients [age 45+/-9 years, duration of
      diabetes 33+/-12 years (mean+/-SD)] with overt diabetic nephropathy participated
      in this study. At both baseline and the end of the study, daytime ambulatory
      blood pressure measurement was performed. Office blood pressure was measured at
      baseline. Additionally, all the patients measured their blood pressure over a 3
      week period using each of the three different devices, in random order, for 1
      week. RESULTS: The mean office blood pressure values (135+/-21/85+/-12mmHg) were
      higher than both the ambulatory (131+/-23/80+/-12, P<0.05) and self-monitoring
      values (130+/-14/78+/-10; P<0.05 for systolic and P<0.02 for diastolic values).
      The difference between the ambulatory and self-monitoring values were not
      statistically significant. Diastolic blood pressure values measured with the
      oscillometric wrist device showed a trend towards higher values when compared to
      those measured with the sphygmomanometer and with the oscillometric upper-arm
      device (P=0.065 for diastolic values). CONCLUSION: Office blood pressure
      measurements may over-estimate blood pressure in patients with type 1 diabetes
      and diabetic nephropathy. Because the oscillometric wrist device tends to over
      estimate diastolic values, upper-arm devices should be preferred for blood
      pressure self-monitoring in these patients.

PMID- 10915232
TI  - Effects of diltiazem retard on ambulatory blood pressure and heart rate
      variability in patients with essential hypertension.
AB  - BACKGROUND: Dihydropyridine calcium antagonists increase heart rate due to reflex
      activation of the sympathetic nervous system, although these effects are less
      obvious for long-acting agents. OBJECTIVE: To study the effects of diltiazem
      retard, a long-acting nondihydropyridine calcium antagonist, on 24h blood
      pressure, heart rate and autonomic nerve activity in patients with essential
      hypertension. DESIGN: Randomized crossover design. METHODS: Thirteen patients
      [five men and eight women, aged 64+/-2 years (mean+/-SEM)] were administered
      placebo or diltiazem retard (100-200mg once daily) for 4 weeks each. Ambulatory
      monitoring of blood pressure and heart rate, and electrocardiography were carried
      out at the end of each period using a multibiomedical recorder (TM-2425).
      Autonomic nerve activity was evaluated by power spectral analysis of variability
      of heart rate using the high-frequency component as an index of parasympathetic
      nerve activity and the ratio of the low-frequency component and the high
      frequency component as an index of sympathovagal balance. RESULTS: Treatment with
      diltiazem retard significantly decreased 24h average blood pressure and heart
      rate by 11.6+/-3.6/5.7+/-1.8mmHg and 5.0+/-1.1 beats/min, respectively. The
      changes in daytime and night-time values were comparable. Diltiazem retard also
      significantly decreased daytime and 24h low:high-frequency-component ratio (2.0+/
      0.2 versus 1.7+/-0.2 and 1. 8+/-0.2 versus 1.6+/-0.2, respectively). CONCLUSIONS:
      These results indicate that diltiazem retard is effective as a once-daily
      antihypertensive agent and has favorable effects on heart rate and the autonomic
      nervous system.

PMID- 10915235
TI  - The Maryland Division of Correction Medical-Parole Program: a four-year
      experience, 1991 to 1994.

PMID- 10915234
TI  - Forum on prisoners' access to clinical trials: summary of recommendations.

PMID- 10915233
TI  - Long-term effects of losartan and enalapril, alone or with a diuretic, on
      ambulatory blood pressure and cardiac performance in hypertension: a case-control
      study.
AB  - BACKGROUND: The long-term effects of angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers on ambulatory blood pressure and cardiac
      performance have never been examined comparatively. OBJECTIVE: We compared
      losartan and enalapril in their long-term effects on office and ambulatory blood
      pressure, cardiac structure and function, and routine biochemical tests. DESIGN:
      In the setting of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale
      (PIUMA) study, 22 hypertensive subjects were studied with ambulatory blood
      pressure monitoring and echocardiography before and after an average of 3.3 years
      of treatment with losartan 50mg daily. These subjects were matched in a 1:3 ratio
      with a group of 66 subjects treated with enalapril 20mg daily. Case-control
      sampling was based on age (+/-5years), sex, pre-treatment office blood pressure
      (+/-5mmHg) and ambulatory blood pressure (+/-5mmHg), and duration of treatment
      (+/-6months). An additional group of subjects who interrupted their treatment
      with enalapril (n=18) or losartan (n =2) because of unwanted effects before
      execution of the follow-up study was not included in the analysis. RESULTS:
      Hydrochlorothiazide was added during follow-up in order to optimize blood
      pressure control (office blood pressure <140mmHg systolic and 90mmHg diastolic)
      in 10 subjects (45%) in the losartan group and 34 subjects (52%) in the enalapril
      group. Office and ambulatory blood pressures were lowered to a similar extent by
      losartan and enalapril. Left ventricular mass decreased from 98 to 87g/m(2) with
      losartan (P <0.01) and from 98 to 89 g/m(2) with enalapril (P <0.01). The change
      in left ventricular mass over time was more closely associated with the change in
      ambulatory blood pressure than with office blood pressure in both groups. Left
      ventricular internal diameter did not change with either drug. The endocardial
      shortening fraction, mid-wall shortening fraction and Doppler indexes of active
      diastolic relaxation did not change with either drug. None of the biochemical
      parameters showed a significant change. Serum uric acid showed a slight and non
      significant reduction only in the losartan group. CONCLUSION: In this case
      control study in uncomplicated subjects with essential hypertension, losartan and
      enalapril, alone or combined with a diuretic, effectively and equally lowered
      office and ambulatory blood pressure and induced a significant reduction in left
      ventricular mass during long-term treatment. Left ventricular systolic and
      diastolic function remained unchanged with either regimen.

PMID- 10915236
TI  - Developing vaccines against HIV: options for accelerated progress.

PMID- 10915237
TI  - Rural HIV-service networks: patterns of care and policy issues.

PMID- 10915238
TI  - Medicaid policies for the physicians' services provided to Medicaid recipients
      with AIDS.

PMID- 10915239
TI  - A duty to care: sterile injection equipment and illicit-drug use.

PMID- 10915240
TI  - Staying negative--it's not automatic: a harm-reduction approach to substance use
      and sex.

PMID- 10915242
TI  - Insurance reimbursement policies and AIDS home healthcare: public and private
      financing mechanisms.

PMID- 10915241
TI  - The role of policy in community pharmacies' response to injection-drug use:
      results of a nationwide Canadian survey.
AB  - The response rate to this survey reflects the salience of the topic and the
      professional concern about and interest in issues presented by HIV. The HIV/AIDS
      epidemic has presented pharmacists with one of the greatest challenges to their
      professional training, ethics, and practice. It further expedites a current re
      examination that is occurring among community pharmacies concerning their roles
      in community health practices. In response to HIV there have been dramatic and
      unprecedented changes in pharmacy policy and practices. Clearly, some community
      pharmacies have led the way and influenced policy and practices. In view of the
      recent introduction of many of these policies and practices, it is likely that
      change will continue. Survey respondents were, in general, very comfortable with
      an expanded role involving counseling, health promotion, and disease prevention,
      consistent with a broader role for community pharmacies in general that has been
      recently advocated. Community pharmacies serve all areas of the country, in
      communities large and small; many are open seven days a week, and some provide
      extended hours of service. Community pharmacies may provide an important
      complement to community outreach programs as a source of clean needles and
      syringes for IDUs in most communities, and as an alternative service in some
      communities where more elaborate programs are not feasible. Safer needle use, as
      part of a health-promotion approach, is divergent from conventional practice.
      While major changes have occurred, it appears that there has been some
      polarization of attitudes and response. The explanation for this is not simple,
      and further analysis is required to determine the full impact from several
      ethical perspectives that include professional, business, and public health
      viewpoints. We have highlighted the role that policy has in moving toward
      preventive and harm-reduction approaches. From a policy perspective, we have
      found that support from the federal government, regulatory bodies, and
      professional associations may be an important catalyst to pharmacists'
      participation in programs. Further, it does not appear to be possible to
      implement such policies without professional development and continuing
      education, and collaboration with the community. Based on data on knowledge and
      educational need, we believe that our study population's lowest levels of
      information were in such areas as the role of methadone in HIV prevention and the
      availability of needle-exchange programs. As with other health-promotion
      campaigns, additional skills training may be important. Movement forward with
      expanded preventive and harm-reduction strategies by pharmacies will require
      careful planning. It is anticipated that change in this area will be incremental
      in nature, and that it is necessary to introduce programs and services into
      community pharmacies gradually. Successful implementation will require extensive
      community development and collaboration with other health professionals, public
      health officials, police, groups who represent IDUs, and persons living with
      HIV/AIDS. Careful monitoring and evaluation of these programs will be necessary
      to enhance their effectiveness.

PMID- 10915243
TI  - Required HIV antibody testing, social risk, and HIV-vaccine efficacy trials.

PMID- 10915244
TI  - One small ethical issue arising in ethnographic research.

PMID- 10915245
TI  - HIV consortia services funded by Title II of the Ryan White CARE Act: a survey of
      the states.

PMID- 10915246
TI  - Syringe-exchange programs in the United States: where are we now?

PMID- 10915247
TI  - AIDS obituaries in the New York Times.

PMID- 10915248
TI  - Model-based allocation of HIV-prevention resources.

PMID- 10915250
TI  - Rethinking HIV counseling and testing.

PMID- 10915249
TI  - On our failure to face the link between drug use and AIDS.
AB  - It is necessary that society accept the medical, neurological basis of compulsive
      drug/alcohol use in order for it to get on with finding and using pragmatic
      approaches to treatment, rather than punishment, as the rational way to deal with
      these issues. The increased availability of oral methadone must be promoted, not
      only because it eliminates the need for drug injection, but because it allows the
      opioid dependent to lead comfortable and functional lives. The emphasis on
      punishment and incarceration for illicit-drug users or purveyors must give way to
      alternatives bent on treatment and rehabilitation. More states should follow the
      example of Connecticut in dealing wisely with drug/AIDS issues.

PMID- 10915251
TI  - Structural impediments to operational syringe-exchange programs.

PMID- 10915252
TI  - Drug-assistance programs funded by Title II of the Ryan White CARE Act: a survey
      of the states.

PMID- 10915254
TI  - The role of cost-effectiveness analysis in assessing HIV-prevention
      interventions.

PMID- 10915253
TI  - Home and community-based care funded by Title II of the Ryan White CARE Act: a
      survey of the states.

PMID- 10915255
TI  - HIV education and prevention in California: problems and progress. HIV Education
      and Prevention Evaluation Team.

PMID- 10915256
TI  - Report from the field: participation of HIV-positive women in clinical research.

PMID- 10915258
TI  - Driving the epidemic underground? A new look at law and the social risk of HIV
      testing.

PMID- 10915257
TI  - Health insurance continuation programs funded by Title II of the Ryan White CARE
      Act: a survey of the states.

PMID- 10915259
TI  - Tradition and experiment in New Zealand AIDS policy.

PMID- 10915260
TI  - Demand for and use of advocacy services for persons living with HIV/AIDS. Four
      Special Projects of National Significance HIV Advocacy Projects.

PMID- 10915261
TI  - The Ryan White CARE Act: the allocation of Title II funding among programs by the
      states.

PMID- 10915262
TI  - The adequacy of reimbursement for HIV under Section 1115 Medicaid waivers.

PMID- 10915263
TI  - Why the U.S. needs a national policy on condoms.

PMID- 10915264
TI  - Mchape: a wake-up call for AIDS control programs in Africa (a case history from
      Malawi).

PMID- 10915265
TI  - The AIDS Litigation Project: HIV/AIDS in the courts in the 1990s, Part 1.

PMID- 10915266
TI  - Tuberculosis and HIV infection: utilization of public programs to fund treatment.

PMID- 10915267
TI  - Determining allocations for HIV-prevention interventions: assessing a change in
      federal funding policy.

PMID- 10915268
TI  - The AIDS Litigation Project: HIV/AIDS in the courts in the 1990s, Part 2.

PMID- 10915269
TI  - The ethics of placebo-controlled trials for perinatal transmission of HIV in
      developing countries.

PMID- 10915270
TI  - The "best proven therapeutic method" standard in clinical trials in
      technologically developing countries.

PMID- 10915271
TI  - Workshop report: AIDS and stigma: a conceptual framework and research agenda.

PMID- 10915272
TI  - HIV surveillance: what's hot, what's not.

PMID- 10915273
TI  - Can access to care for people living with HIV be expanded?

PMID- 10915274
TI  - The perceptions and experiences of managed care by HIV-positive individuals in
      New York City.

PMID- 10915275
TI  - Testing the force: HIV and discrimination in the Australian military.

PMID- 10915276
TI  - Healthcare for the drug-dependent Americans.

PMID- 10915277
TI  - Bragdon v. Abbott: who's in? Who's out?

PMID- 10915278
TI  - Economic and geographic diversity in AIDS incidence among HIV exposure groups in
      New York City: 1983 to 1995.

PMID- 10915279
TI  - Cost-effectiveness analysis and HIV prevention community planning.

PMID- 10915280
TI  - The ethics of needle-exchange programs.

PMID- 10915281
TI  - Expanding access to PEP: ethical and legal issues.

PMID- 10915282
TI  - Organizational imperatives and policy perspectives of AIDS community-based
      organizations: a view from the states.

PMID- 10915283
TI  - Justice and access to therapies for AIDS.

PMID- 10915284
TI  - Morals, methods, and neutrality in human-subject research.

PMID- 10915285
TI  - Toward a systematic understanding: a two-way relational model between drug use
      and HIV/AIDS.

PMID- 10915286
TI  - Perspectives in conflict: the response to transfusion-associated AIDS.

PMID- 10915287
TI  - Examining medical coverage for Medicare beneficiaries with HIV/AIDS.

PMID- 10915288
TI  - Military HIV-prevention education: the use of evaluation to inform the evolution
      of policy.

PMID- 10915289
TI  - Washington insight. An inconvenient analysis.

PMID- 10915290
TI  - New concepts in health benefits. Three-tier drug copays.

PMID- 10915292
TI  - Depression in the workforce: seeing the cost in a fuller light.

PMID- 10915291
TI  - Do American hospitals get away with murder?

PMID- 10915293
TI  - Checking up on the executive physical.

PMID- 10915294
TI  - Reproductive health: questions of equality.

PMID- 10915295
TI  - Working around the clock.

PMID- 10915296
TI  - Technology. Part II: New opportunities for health care?

PMID- 10915297
TI  - Health care 2010's "long boom" trends.

PMID- 10915298
TI  - How to look really far ahead.

PMID- 10915299
TI  - 12 critical questions for at-risk organizations.

PMID- 10915300
TI  - California medical group wins big even in tight contracting market.
AB  - Hill Physicians Medical Group is one of the most highly regarded provider
      organizations doing capitated deals in the cut throat northern California market.
      What makes this group tick?

PMID- 10915301
TI  - Study makes case for integrating behavioral health, primary care.
AB  - Data Insight: Rising health care costs and high rates of comorbidity between
      psychological and chronic physical illnesses are prompting some organizations to
      integrate behavioral health services in the primary care setting, prompting a
      need for new models of reimbursement and risk-sharing.

PMID- 10915302
TI  - Make sure your reinsurance policy matches your risk profile.
AB  - Stability and predictability are the main reasons for using a combination of
      surplus and reinsurance to cushion the impact of large-claims cases. But how much
      of each is needed?

PMID- 10915303
TI  - An overview of risks from the operation of hospital building services.

PMID- 10915304
TI  - Royal Free Hospital has effective plant room door control.

PMID- 10915305
TI  - The right mix for mental health.

PMID- 10915306
TI  - Re-thinking hospital construction.

PMID- 10915307
TI  - Maintenance and the life expectancy of healthcare equipment in developing
      economies.
AB  - Measuring the economic viability of systematically maintaining physical assets
      (buildings, utilities, medical equipment) in healthcare is important in emerging
      economies with limited resources. This paper puts forward a way to estimate the
      benefit by comparing the input for maintenance with the savings achieved by
      extending the useful life of physical assets. For this purpose, life expectancies
      have been studied under conditions with and without systematic maintenance based
      on a planned and preventative approach for a selection of utilities and medical
      equipment. The result shows that the average prolongation of useful life for
      healthcare equipment in emerging economies is about two-fold. Specific figures on
      the life expectancy of 16 different items are presented. Finally, recommendations
      are given on how to employ the method locally.

PMID- 10915308
TI  - We all fall down--preparing for a disaster.

PMID- 10915309
TI  - Mixing medicine and entertainment. TV confronts its role as health educator.

PMID- 10915310
TI  - Schools fight fat by teaching kids to eat their greens.

PMID- 10915311
TI  - Herbs and prescriptions can make a risky mixture.

PMID- 10915312
TI  - The HEC model of the future builds on deficiencies of the past.

PMID- 10915313
TI  - Corporate soulcraft in healthcare: the St. Joseph Health System's "compliance
      assurance" approach, and other options.

PMID- 10915314
TI  - Changing the HEC mission.

PMID- 10915315
TI  - A next-generation ethics program in progress: lessons from experience.

PMID- 10915316
TI  - Ethics and economics in healthcare: the role of organization ethics.

PMID- 10915317
TI  - Outline of a process for organizational ethics consultation.

PMID- 10915318
TI  - Professional codes and healthcare decisions: a pilot study of the role played by
      professional codes of ethics in decisionmaking by healthcare professionals.

PMID- 10915319
TI  - Reinventing the Healthcare Ethics Committee.

PMID- 10915320
TI  - Should the HEC have the primary responsibility for developing a specific ethical
      vision for the institution? Yes.

PMID- 10915321
TI  - Should the HEC have the primary responsibility for developing a specific ethical
      vision for the institution? No.

PMID- 10915322
TI  - Informed consent and truth telling: the Chinese Confucian moral perspective.

PMID- 10915323
TI  - Vaccines and immunization performance measures.

PMID- 10915324
TI  - Skin cancer prevention in outdoor recreation settings: effects of the Hawaii
      SunSmart Program.
AB  - CONTEXT: Skin cancer is the most common form of cancer in the United States, and
      it is one of the most preventable. Interventions for young children and their
      parents can help prevent future cases of skin cancer. OBJECTIVE: To determine
      whether a skin cancer prevention program implemented at outdoor recreation sites
      improved children's sun-protection behaviors and site sun-protection policies.
      DESIGN: Randomized trial of 14 outdoor recreation sites on the island of Oahu,
      Hawaii. The trial had three arms: control, education only, and
      education/environment. INTERVENTION: The education arm included staff training,
      on-site activities, take-home booklets, behavior-monitoring boards, and
      incentives. The education/environment arm included all education components plus
      provision of sunscreen and promotion of sun-safe environments. PARTICIPANTS:
      Children 6 to 8 years of age and their parents. OUTCOME MEASURES: Reports from
      parents of children's sun-protection behaviors and the sun-protection policies of
      recreation sites. The cohort for analysis from baseline to 6 weeks after testing
      had 383 participants; the cohort from 6 weeks after testing to 3 months of follow
      up had 285 participants. RESULTS: Program implementation was high in the
      education only and the education/environment sites. Compared with control sites,
      children's sun-protection behaviors and, in particular, the use of sunscreen
      improved significantly at sites where the two interventions were implemented. In
      addition, sun-protection policies of recreation sites were markedly higher at
      intervention arm sites. The education/environment intervention was not superior
      to education alone. Changes were partly maintained at 3 months of follow-up.
      CONCLUSION: A creative, engaging, multicomponent skin cancer prevention program
      in outdoor recreation settings can lead to modest improvements in children's sun
      protection behaviors.

PMID- 10915325
TI  - The influence of organizational structure on physician satisfaction: findings
      from a national survey.
AB  - BACKGROUND: The term managed care encompasses a variety of organizational
      arrangements between physicians and health plans. At one extreme, physicians are
      plan employees; at the other, physicians have contracts with multiple plans. How
      these arrangements affect physicians' satisfaction with managed care is not well
      known. OBJECTIVE: To explore the effect of organizational structure on physician
      satisfaction. DESIGN: Telephone survey of 751 practicing internists. The response
      rate for the 15-minute survey was 64%. SAMPLING STRATEGY: The random sample was
      taken from the membership of the American College of Physicians-American Society
      of Internal Medicine. Federal employees, retirees, physicians, and students who
      spent less than half of their time in patient care were excluded. RESULTS: 689
      Physicians indicated that they were affiliated with a managed care plan: 9% were
      salaried employees, 6% had an exclusive contract with one plan, and 85% had a
      variety of nonexclusive arrangements with multiple plans. Among plan employees,
      32% reported they were very satisfied with the managed care organization in which
      they worked. The corresponding figure was 19% among physicians with an exclusive
      contract and 5% among those with multiple contracts. A similar pattern of
      responses was seen when physicians were asked about their perception of the
      commitment of managed care to quality. Although 64% of plan employees responded
      that there was a great deal of commitment, the corresponding figure was 35% among
      physicians with an exclusive contract and only 7% among those with multiple
      contracts. CONCLUSIONS: Physicians who are salaried employees of a staff- or
      group-model HMO report the highest satisfaction with managed care.

PMID- 10915326
TI  - Variations among hospitals in the quality of care for heart failure.
AB  - CONTEXT: Determining variations in quality of care among hospitals can help
      direct attention to poorly performing institutions. PRACTICE PATTERN EXAMINED:
      The proportion of patients with congestive heart failure meeting various quality
      criteria in 69 hospitals. HOSPITAL SELECTION: The hospitals were voluntary
      participants in a quality improvement program in five states (Colorado,
      Connecticut, Georgia, Oklahoma, and Virginia). PATIENT SELECTION: All patients
      with congestive heart failure discharged from the participating hospitals during
      a 15-month period in 1995 to 1996 (or, for hospitals with more than 50 eligible
      patients, a random sample of 50 patients). The total sample consisted of 2077
      patients. DATA SOURCE: Documentation in the hospital medical record of left
      ventricular function, discharge medications, and discharge instructions. RESULTS:
      Left ventricular function was determined in 72% of patients (range across
      hospitals, 18% to 97%). Among patients with left ventricular systolic
      dysfunction, 79% were prescribed an angiotensin-converting enzyme inhibitor
      (range, 54% to 94%). Only 23% of the patients prescribed angiotensin-converting
      enzyme inhibitors received the target dose (range, 0% to 60%). Sixty-four percent
      of patients were counseled about the importance of a low-sodium diet at discharge
      (range, 25% to 97%), but only 8% were counseled about daily weight monitoring
      (range, 0% to 30%). CONCLUSION: Our results show substantial hospital-to-hospital
      variation in the quality of care for patients with heart failure.

PMID- 10915327
TI  - When should we stop screening?
AB  - CONTEXT: Although the age at which screening should be started is the subject of
      considerable debate, the question of when to stop has received little attention.
      COUNT: Days of life lost by stopping screening at various ages. CALCULATIONS: For
      each of three types of cancer (breast, cervical, and colon), we used life tables
      to calculate life expectancy at various ages for stopping screening and for
      continuing screening until death. The days of life lost by stopping screening is
      the difference in life expectancy between the two life tables for a specified
      age. DATA SOURCES: All-cause and cancer-specific mortality were obtained from the
      National Center for Health Statistics and Surveillance Epidemiology and End
      Results Survey (SEER). ASSUMPTIONS ABOUT BENEFIT: On the basis of randomized
      trial data, we used a 30% reduction in cancer-specific mortality for breast and
      colon cancer screening. Because there are no comparable data for cervical cancer,
      we assumed a 30% reduction in the mortality rate for the "best-guess" analysis
      and a 70% reduction in the mortality rate for the "best-case" analysis. We
      assumed that these benefits persisted for the elderly. ASSUMPTIONS ABOUT HARM: We
      assumed that there was no harm with screening. RESULTS: Given a starting age of
      50 years, screening throughout life has a maximum potential life expectancy
      benefit of 43 days for breast cancer and 28 days for colon cancer. The average 75
      year-old who stops either mammography or fecal occult blood testing would give up
      a maximum of 9 days. By stopping at age 80, she would give up a maximum of 5
      days. Given a starting age of 20, Pap smear screening has a maximum potential
      benefit of 47 days in the best-case analysis and 7 days in the best-guess
      analysis. The average 75-year-old who forgoes Pap smear screening would give up a
      maximum of 3 days (best case) or 0.5 days (best guess). By stopping at age 80,
      she would give up a maximum of 1.5 days and 0.2 days, respectively. CONCLUSIONS:
      Even assuming that the mortality reduction with screening persists in the
      elderly, 80% of the benefit is achieved before 75 years of age for breast cancer,
      80 years for colon cancer, and 65 years for cervical cancer. The small benefit of
      screening in the elderly may be outweighed by the harms: anxiety, additional
      testing, and unnecessary treatment.

PMID- 10915328
TI  - Grading the evidence for diabetes performance measures.
AB  - CONTEXT: Grading scientific evidence is a critical step in developing practice
      guidelines and quality performance measures. GENERAL QUESTION: What is the most
      useful way to grade evidence? SPECIFIC QUESTION: How should we grade the
      recommended clinical practices for patients with diabetes? STANDARD APPROACH:
      Hierarchical grading systems (e.g., grades I, II, and III), such as that used by
      the U.S. Preventive Services Task Force, have traditionally been used to rank the
      research designs of studies that support a particular clinical practice.
      POTENTIAL DIFFICULTIES: Many studies that support the clinical practices of
      diabetes care do not clearly conform to the categories traditionally used in
      hierarchical grading systems. As a result, there is a tendency to inaccurately
      characterize the level of evidence, leading to the phenomenon of evidence
      inflation or evidence deflation. To avoid exaggerating the evidence, important
      sources of information may be excluded, resulting in an understatement of the
      available supporting evidence. ALTERNATE APPROACH: This paper offers a more
      descriptive typologic system that uses the study design and an explanatory
      modifier to grade the evidence supporting the clinical practices of diabetes
      care. The study grades are randomized, controlled trial (RCT); RCT-embedded
      component; RCT-treatment only; RCT-different population; observational study-risk
      factor; and expert opinion. Using this grading system, the authors were able to
      more accurately describe the best available evidence supporting the clinical
      practices of diabetes care.

PMID- 10915329
TI  - The bright side of the managed care "dark side" demon.

PMID- 10915330
TI  - Arguing about grades.

PMID- 10915331
TI  - Primer on interpreting surveys.

PMID- 10915333
TI  - Telemedicine: the cyber physician and credentialing.

PMID- 10915332
TI  - If you care about women's health, perhaps you should care about the risks of
      direct marketing of tamoxifen to consumers.

PMID- 10915334
TI  - The role of arbitration in resolving medical malpractice disputes: will a well
      drafted arbitration agreement help the medicine go down?

PMID- 10915335
TI  - Problem employees and employee problems.

PMID- 10915336
TI  - The changing face of health care management.
AB  - In health care as elsewhere, the only constant is change. Change has been
      especially rapid in health care, forcing dramatic changes in the way health care
      managers work. Management style in health care may or may not be different from
      that in other industries; its determinants are related primarily to certain
      universal characteristics that may be present in many businesses but have one
      dimension in common: immediacy of the customer (that is, hands-on, face-to-face
      service). Health care management has had to change considerably in the past 30
      years and will be required to change further still in the years to come. In
      changing with the industry, the role of the health care manager will include
      enhanced span of control and increased authority and responsibility, and thus
      greater accountability. Given the changing nature of the environment, the most
      valuable characteristics of tomorrow's health care manager will be flexibility
      and adaptability.

PMID- 10915337
TI  - Gender differences in leadership in the health professions.
AB  - The leadership characteristics and behaviors of men and women differ. As
      increasing numbers of women enter positions of leadership, understanding of these
      differences can increase the quality and productiveness of relationships in the
      workplace. This article describes the evolution of women in leadership, gender
      differences in leadership style, and the way gender may affect behaviors in the
      workplace.

PMID- 10915338
TI  - Health care alliances and alternative dispute resolution: managing trust and
      conflict.
AB  - The U.S. health care industry has entered an unprecedented era of alliance
      activity. These alliances involve medical groups and hospitals, as well as many
      of the newer health care entities such as managed care organizations and
      integrated delivery systems. The increase in organizational collaboration has
      resulted in an increase in organizational conflict. Alternative dispute
      resolution (ADR) techniques can serve as a valuable tool for mitigating this type
      of conflict. The role of ADR is to refocus partners' attentions away from an
      adversarial posture and toward a complementary existence. This will permit the
      partners to realize the intended outcomes of the collaboration.

PMID- 10915339
TI  - Recruiting good employees in tough times.
AB  - In tough hiring times, health care employers must develop a fresh approach to
      their recruitment techniques and practices in order to capture a desired segment
      of the labor market. While some of these techniques and practices are new, many
      are a variation of conventional ones. Successful organizations will
      simultaneously use a variety of methods, thus enabling them to recruit good
      employees continually. A tight labor market requires that organizations become
      creative recruiters.

PMID- 10915340
TI  - "The orphan supplies".

PMID- 10915341
TI  - One more time: please fire marginal employees.
AB  - Managers should not second-guess themselves when contemplating termination of
      marginal employees, i.e., those with sustained poor attitudes or performances.
      Poor performers should not be allowed to disadvantage an otherwise successful
      team; management ought not to retain someone it cannot fully support; and
      termination may be interpersonally excruciating but is organizationally very
      invigorating. This article identifies ten reasons why marginal employees prevail
      and are not dealt with in organizations. Acknowledging these barriers is a
      valuable first step in moving from analysis to synthesis as concerns removing
      them in the future.

PMID- 10915342
TI  - Renewal versus burnout: a career blueprint.
AB  - The art of renewal keeps managers and supervisors enthused and excited about what
      they do. Renewal preserves the sense of purpose that managers and supervisors
      bring to their jobs and careers. Renewal can be learned and is based on the basic
      theories of motivation and coping. This article serves as a review for veteran
      managers and supervisors and as a primer for new managers and supervisors.

PMID- 10915343
TI  - Electronic medical records and patient privacy.
AB  - Networks of health care providers and payers increasingly rely upon electronic
      databases to coordinate and analyze medical information. Benefits of linking
      databases include saving lives and reducing costs. However, access to and use of
      medical records raise serious privacy concerns. Potential misuse of records may
      harm patients and undermine the quality of health care. In the clinical setting,
      stringent security procedures must be instituted, including limited access to
      electronic records, audit trails, and security audits. Patient consent should be
      obtained before personal information is disclosed. Current law does not provide
      the strong, consistent guidelines needed. Adequate privacy protection requires a
      comprehensive federal law.

PMID- 10915344
TI  - Speak up: the manager's guide to oral presentations.
AB  - Public speaking is a skill that can prove to be of considerable value to health
      care managers, yet a great many managers have not been trained as speakers and
      thus tend to avoid speaking situations or approach them with fear and doubt.
      However, any working manager can become an effective speaker through conscious
      effort to do so. The keys to developing one's ability to deliver effective oral
      presentations are preparation and practice. Preparation includes knowing one's
      subject and one's audience, appropriately organizing the material, learning how
      to present information according to what one wishes to convey or accomplish,
      learning how to use visual aids, and working to improve one's manner of using
      language in a public setting. Beyond following the guidelines for appropriate
      preparation and delivery, success and a degree of comfort with public speaking
      comes with practice, practice, practice.

PMID- 10915345
TI  - A manager asks: taking advantage of the gray areas.

PMID- 10915346
TI  - HFMACertification.Com.

PMID- 10915347
TI  - HIPAA is coming, but is the sky falling?

PMID- 10915348
TI  - Home health programs will continue to add value under PPS.
AB  - As the October 1, 2000, implementation date for the home health prospective
      payment system approaches, healthcare organizations that include a home health
      component need to decide whether they will continue offering home health
      services, and if so, how to ensure that these services are profitable. To
      determine which services should be continued, these organizations need to analyze
      each home health business line in terms of utilization and profitability,
      comparing performance under cost-based payment with projected performance under
      prospective payment. The organization then should formulate a strategic action
      plan for rapidly developing the optimum home health network.

PMID- 10915349
TI  - HMO contracting strategies: protecting the provider's interests.
AB  - Managers of provider organizations who understand HMOs' motivations and
      negotiating strategies will be better prepared to negotiate contracts that serve
      the interests of their organizations. Information that may strengthen a
      provider's negotiating position with an HMO, such as the HMO's historic and
      projected general administrative costs, inflation factors, and utilization rates,
      can be obtained from the proposed premium rates HMOs must file with their state
      departments of insurance or from HMO annual statements. Providers also should
      make sure that their contracts give them the right to regularly review the HMO's
      database of information relating to the provider's costs and revenues. Without
      this information, the roots of problems may be obscured, leaving providers with
      no opportunities to turn around a negative situation.

PMID- 10915350
TI  - Getting tough with home health accounts receivable.
AB  - Home health organizations seeking to improve the performance of their accounts
      receivable should concentrate first on establishing practices that promote the
      greatest percentage of clean claims and reviewing payments received to be sure
      rates paid are optimal. They also may find it worthwhile to survey their business
      office operations for potential improvements to key areas.

PMID- 10915351
TI  - Leadership skills help financial managers achieve career success.
AB  - Financial managers who want to distinguish themselves in their organizations need
      to demonstrate their leadership ability. Because financial managers sometimes
      overlook the need for leadership skills, cultivating mentors who can teach them
      specific leadership skills, such as improved communications and entrepreneurship,
      may be necessary. Healthcare financial managers can sharpen their leadership
      skills by distinguishing between leadership and management, adopting a new
      mentoring model, evaluating the usefulness of new management techniques,
      understanding the connection between technology and leadership, looking for the
      solution beyond the problem, and being seen and heard within the organization.

PMID- 10915352
TI  - Will your compliance plan pass the effectiveness test?
AB  - A healthcare organization that has a dynamic compliance plan that is regularly
      reviewed, revised, and followed is more likely to be in compliance with Federal
      and state laws and regulations. Healthcare financial managers should be guided by
      the criteria for compliance plans set forth by the Department of Justice and the
      Office of Inspector General in their "Compliance Program Guidance for Hospitals."
      An independent audit of the compliance plan is recommended, but a careful
      internal examination of the plan should be performed before the independent audit
      takes place. It is important to determine how well the plan is followed, revise
      the plan if necessary, and document actions taken to fulfill the plan's
      requirements.

PMID- 10915353
TI  - Measuring the value of healthcare business assets.
AB  - Healthcare organizations obtain valuations of business assets for many reasons,
      including to support decisions regarding potential mergers, sale of business
      components, or financing; for tax assessments; and for defense against law-suits.
      If compliance with regulations may be an issue, such as when a not-for-profit
      organization is involved in a transaction, healthcare organizations should seek
      an independent appraisal to ensure that applicable legal standards are met.
      Whether or not regulatory issues are involved, however, an accurate and useful
      valuation of business assets depends on many factors. Financial managers must
      understand the purpose and function of the valuation, choice of appropriate
      valuation techniques, proper assessment of intangible value, use of realistic
      growth rates, appropriate emphasis on key focus areas of the valuation (e.g.,
      risk and future income streams), and an accounting of physician compensation.

PMID- 10915354
TI  - Telemedicine can lower costs and improve access.
AB  - Communications technology is being used increasingly for telemedicine
      applications to improve access to medical care in rural areas. The most cost
      effective applications are those that are paid for by insurers, such as the use
      of telemedicine for radiology, prisoner health care, psychiatry, and home health
      care. Other applications enhance access to care but are not cost-effective
      because third-party payers do not pay for related costs for professional fees or
      the implementation of the technology. Before implementing telemedicine programs,
      healthcare providers should determine whether they would receive a reasonable
      return on investment by evaluating all associated costs and estimating the amount
      of payment they can expect. As the use of telemedicine services increases, it is
      expected that third-party payers will pay for more of these services to control
      medical costs.

PMID- 10915355
TI  - Supreme Court limits provider challenges to Medicare policy.

PMID- 10915356
TI  - PFS managers well positioned to lead HIPAA implementation.

PMID- 10915357
TI  - HIPAA compliance offers human resource department savings.

PMID- 10915358
TI  - Fine-tuning information systems to enhance performance.

PMID- 10915359
TI  - Medicare "fairness" robs Peter to pay Paul.

PMID- 10915360
TI  - Focused on the big picture: an interview with Jerry P. Widman.

PMID- 10915361
TI  - Effective real estate management helps IDSs meet strategic objectives.
AB  - As IDSs expand their healthcare delivery networks, they acquire an increasingly
      diverse array of real estate assets. Managing these assets effectively requires a
      comprehensive real estate strategy. To develop such a strategy, the IDS should
      form a strategic real estate planning team. The team's role should be to conduct
      market research; assess the strategic value of the IDS's real estate portfolio;
      recommend strategies for disposing of unnecessary, underperforming, or mis
      aligned assets; evaluate new real estate acquisitions or development projects
      that may be required to achieve the organization's mission and/or protect market
      share; and recommend a financing approach that fits the real estate strategy.

PMID- 10915362
TI  - Managed care strategic planning: the reality of uncertainty.
AB  - The unpredictable future of the managed care industry has led to strategic
      planning paralysis in some organizations. The lack of a strategic plan can be
      damaging to an organization's long-term viability. In developing a managed care
      strategic plan, an organization should have a basic understanding of its
      environment and its ability to make changes as indicated by its structure and
      information system capabilities. If the organization is both strong and flexible
      in these two areas, it is well positioned to thrive in the turbulent managed care
      environment. Strategic plans need to consider alternate futures, reinforce the
      organization's vision, support the organization's long-term financial viability,
      and incorporate the reality of the industry's uncertain future.

PMID- 10915363
TI  - Information technology: doing more, spending less.
AB  - Few hospitals use their increasingly limited financial resources to successfully
      realize all the benefits of information technology (IT). Part of the problem in
      achieving success is that hospitals waste funds by, for example, allowing
      "temporary" consultants to become long-term, full-time fixtures in the IT
      department. Or the organizations create conditions for failure by overstaffing or
      understaffing their IT departments or opting to invest in pilot or beta
      technology of unproven worth. Healthcare finance executives need to scrutinize
      the IT expenditure requests they receive and evaluate the realistic return on
      investment. They also need to conduct audits of their IT contracts and invoices
      to ensure they are not paying unnecessary or invalid fees.

PMID- 10915364
TI  - Automated charge processing streamlines data entry.
AB  - A healthcare organization can significantly improve its billing office's
      performance by implementing an automated charge-processing system that integrates
      scanning technology with hospital and physician office billing systems. Such a
      system offers large healthcare organizations a means to eliminate costly and
      inefficient manual processing of paper charge sheets, thereby improving
      productivity and accuracy. An automated charge-processing system allows a billing
      department to automatically post, track, monitor, control, and reconcile all
      charges through a central database. To implement the system, a healthcare
      organization should assemble a project team composed of representatives from
      information services, the software supplier, and the organization's business
      offices. The team will be responsible for setting up the system; designing an
      easily scannable, standard charge form; establishing the rules the system will
      follow for posting charges; and designing billing office reports.

PMID- 10915365
TI  - Benchmarking facilitates process improvement in the emergency department.
AB  - The emergency department (ED) is an important source of revenue for hospitals.
      Patient satisfaction is necessary to any effort to optimize revenues. If patients
      fail to move efficiently through the ED, their perception of the experience might
      be negative. To facilitate process improvement in the ED, hospitals need to
      identify critical success factors and appropriate measures, collect data on their
      patient-flow process, compare those data with industry benchmarks, and then
      determine areas for improvement. With this information, an action plan can be
      designed to improve patient-throughput time and patient satisfaction without
      lowering the quality of care delivered.

PMID- 10915366
TI  - Making corporate compliance programs work.
AB  - Healthcare organizations have created corporate compliance programs in an effort
      to adhere to Federal government recommendations, minimize the risk of wrongful
      behavior, and possibly reduce fines that may result from a government
      investigation. Compliance programs may have undetected weaknesses. Corporate
      compliance officers, executives, and board members need to be certain that their
      organization's program has sufficient infrastructure, oversight, and resources;
      effective education and training; an effective mechanism (hotline) to receive
      reports of compliance problems; and ongoing auditing and monitoring capabilities.

PMID- 10915367
TI  - Capital financing options for group practices.
AB  - Group practices that are looking for capital partners need to demonstrate that
      they have the necessary management capability to operate a successful business
      capable of repaying the debt. Two basic types of debt financing are available to
      group practices: fixed-rate financing and variable-rate financing. Fixed-rate
      financing, the more common method, involves borrowing a specific amount of money
      and then paying off the debt in principal-and-interest payments, much like a
      fixed-rate mortgage. Variable-rate financing, on the other hand, involves
      obtaining a letter of credit from the lender itself or independent guarantor to
      secure a loan. The variable-rate method is more efficient and flexible, because
      the notes secured by the letter of credit can be rated independently and sold
      into public capital markets like short-term, variable-rate paper. Both types of
      financing can require the personal guarantee of all physicians in the group
      practice.

PMID- 10915368
TI  - OIG audit of HCFA prompts steps to reduce payment errors.

PMID- 10915369
TI  - Ways to reduce inventory.
AB  - Almost every business today is looking for ways to reduce inventories. However,
      the unsaid goal is to reduce that inventory while at the same time maintain or
      improve customer service. Today, every business operation is concerned with
      methods to improve customer service. The real trick is to accomplish that task
      without increasing inventory. This article discusses how some of the leading
      companies accomplish the task of reducing inventory and increasing customer
      service at the same time.

PMID- 10915370
TI  - Inventory management within the supply chain.
AB  - How can a company reduce its inventory costs as much as 35 to 50% of its current
      assets? The key to reducing inventory is to evaluate the entire supply chain,
      including an assessment of procurement, production, and distribution.

PMID- 10915371
TI  - What it takes to implement and maintain successful supplier-managed inventory
      programs.
AB  - Besieged by global competition and rapid technology changes, manufacturers
      subsequently have increased pressures on their suppliers to deliver product in
      less than traditional lead-times. In order to accomplish this goal, the proper
      selection of suppliers and inventory management programs is paramount. This
      article will focus on the selection of suppliers, what it takes to make the
      programs successful, and the most popular types of supplier-managed inventory
      programs in today's high-technology marketplace.

PMID- 10915372
TI  - Discover the missing links in the inventory knowledge chain--achieve 98%
      integrity in just 90 days? Yes you can!
AB  - You don't need any imagination to understand how to reconnect the Missing Links
      in the Knowledge Chain to improvement. The corrective action plan has been
      described clearly in eight easy steps that everyone can and should execute
      immediately to get their inventory integrity permanently up to 95 to 98% and keep
      it there. Nothing has been left to the imagination or to conjecture. This is the
      "how to" prescription to getting it done. It has worked effectively for others.
      It can work for you too.

PMID- 10915373
TI  - Building strategic alliances: a case study.
AB  - It takes much coordination, communication, patience, and persistence to build and
      manage supplier partnerships in order to lower total costs, reduce lead times,
      improve the quality of products, optimize inventories, and streamline
      administrative process. In the absence of the latest technology, it takes
      talented and enthusiastic team members who take pride in their work, who can
      think progressively, who can generate optimism in any situation, and who can
      maintain grace under pressure in order to be successful.

PMID- 10915374
TI  - Earning supplier partnerships through principled negotiations.
AB  - In today's competitive global village, we must be prepared to do things
      differently than in the past if we wish to survive as a manufacturing economy. If
      purchasing is to do its part, running away from the problems will not solve the
      problems. We must learn how to work with our suppliers in a much more productive
      fashion than ever before. Supplier partnerships are indeed part of the answer to
      this change. But without changing the way we deal with suppliers, we'll never get
      the improvements that are possible.

PMID- 10915375
TI  - Advanced supplier partnership practices: a case study.
AB  - This article describes how a supplier partnership was set up to avoid the typical
      purchasing relationship--price being inversely proportional to quantity and
      having the purchaser take all the risk of product obsolescence. The case study
      also describes how rate-based replenishment replaced time-based delivery, and how
      all these advantages were achieved at reduced administrative costs.

PMID- 10915376
TI  - Making consignment- and vendor-managed inventory work for you.
AB  - This article will examine some of the benefits of vendor managed inventory (VMI)
      and consignment from a supplier's perspective. Indeed, there are benefits to both
      approaches, as well as costs and risks. By understanding and managing the costs,
      and controlling the risks through careful negotiations, one can make both
      consignment and VMI work not only for the customer, but for the supplier as well.

PMID- 10915377
TI  - Lead time reduction: the catalyst for world-class results.
AB  - With the objective of reducing lead times as much as possible, many process
      improvements can be made. Without the objective of lead time reduction, there can
      be many confusing objectives without a common thread. This usually results in
      poor achievement scores on many objectives. To accomplish one major objective,
      lead time reduction, all other areas will and must be addressed but by a united
      work force working towards one common goal.

PMID- 10915378
TI  - How measurement systems act as employee motivators.
AB  - A research project funded in part by APICS studied the relationship between
      measurement systems and how they motivate company performance. The research
      involved surveys, interviews, and a case project. This article will be a status
      update of the findings of this research.

PMID- 10915379
TI  - Quality improvement through root cause analysis.
AB  - By preventing the recurrence of errors in service delivery or manufacturing
      processes, significant improvements in both productivity and quality are assured.
      By eliminating nonconformance in the system through zero defects and anticipating
      and preventing errors prior to process implementation, significant cost savings
      may be realized to positively impact the organization's profit margin. With an
      understanding of the environment necessary to create quality, organizations will
      identify solutions to costly, recurring problems.

PMID- 10915380
TI  - Achieve inventory reduction and improve customer service?
AB  - Is it really possible to achieve significant reductions in your manufacturing
      inventories while improving customer service? If you really want to achieve
      significant inventory reductions, focus on the root causes, and develop
      countermeasures and a work plan, to execute your countermeasures. Include
      measurements for recording your progress, and deploy your countermeasures until
      they are no longer required, or until new ones are needed.

PMID- 10915381
TI  - A framework for doctoral education in health administration and policy.
AB  - The fundamental building block upon which the whole edifice of education for
      health services administration rests is doctoral education. Programs can be no
      better than the quantity and quality of doctoral graduates available to them. In
      turn, these graduates can be no better than the programs in which they were
      trained. The purpose of the present paper is to propose a framework for analyzing
      five different types of doctoral programs in health services administration and
      policy. First, five models of doctoral education in health services
      administration and policy are proposed and described. Second, the advantages and
      disadvantages of each of these models are described fro the viewpoint of the
      producer. Third, the most appropriate matches of program types and customer
      orientations are outlined. The basic premise of the paper is that the employers
      of doctoral graduates occupy (implicitly or explicitly) a limited set of market
      niches. No single doctoral program can meet the needs of all potential employers.
      Nor should the potential employer expect that all program types will produce
      graduates equally capable of meeting their needs.

PMID- 10915383
TI  - Andrew Pattullo Lecture. Health future: the managerial agenda.

PMID- 10915382
TI  - Integrating the Internet into health administration education: a report from
      AUPHA's Faculty Internet integration task force.
AB  - HRSA funded a survey to determine what Internet resources would be most useful to
      AUPHA membership. This manuscript describes the Internet-intensive survey
      methodology, reports the survey results, and lists the task force
      recommendations. The task force used sequential questionnaires posted on the Web
      to gather both potentially useful Internet resource ideas and membership
      perceptions of the importance of each idea. Resources recommended by survey
      participants and the Task Force members emphasized potential improvements to the
      AUPHA and AUPHA-member Web pages.

PMID- 10915384
TI  - The Baxter Allegiance Prize address. National medical expenditure surveys: a
      legacy for health services research.

PMID- 10915385
TI  - CEO outlook regarding ACEHSA and AUPHA.

PMID- 10915386
TI  - The roles of the public and private sectors in health care.

PMID- 10915387
TI  - An antidote for ailing TV ad testing measures and spiraling medical costs.

PMID- 10915388
TI  - A model of strategic marketing alliances for hospices: horizontal alliances.
AB  - This article develops two previous research efforts. William J. Winston (1994,
      1995) has proposed a set of strategies by which health care organizations can
      benefit from forging strategic alliances. Raadt and Self (1997) have proposed a
      classification model of alliances including horizontal, vertical, internal and
      osmotic. In the first of two articles, this paper presents a model of horizontal
      alliances. The subsets include transregional, service mergers, networks, venture
      capital investments, trade and professional organizations, and promotional
      alliances. Advantages and disadvantages of each are discussed.

PMID- 10915389
TI  - Quality, sacrifice, and value in hospital choice: a comparative study of rural
      and suburban consumer perspectives.
AB  - This research examines consumers' value perceptions and their role in hospital
      choice behavior in rural and suburban markets. While health care markets are
      "local," this study confirms the broad efficacy of a value-based approach to
      understanding consumer choice of providers.

PMID- 10915390
TI  - Health care policy reform: a microanalytic model for comparing hospitals in the
      United States and Germany.
AB  - Microcomparison, or single-component analysis, of health care systems offers a
      potentially better basis for reform than traditional macrocomparison analysis of
      aggregate elements. Using macroanalysis, available evidence shows that Germany
      provides cheaper but more effective hospital care than the United States. To find
      the causes for this outcome, we developed a microanalytic model of hospital
      administrators' perceptions, financial ratios, medical outcomes, and
      pharmaceutical costs. However, only data on pharmaceutical costs were available,
      and these were similar in both countries. Our significant outcome was development
      of a microcomparative model that gives world medical care providers new criteria
      for analyzing and improving cost to care ratios.

PMID- 10915391
TI  - The dilemma of conflicting attitudes: survey results or community perceptions?
AB  - This present article investigates conflicting community attitudes and formal
      survey results. The survey results suggest that patients viewed their physicians'
      and nurses' competency and care very highly, as well as receiving satisfactory
      care in specialized departments. The results further suggest that hospital meals
      were less satisfactory in terms of patient enjoyment of meals and with the
      services of the dietitian. However, one major area of concern was the low number
      of survey responses and the recommendations that are made for improving the
      response rate. Demographic inconsistencies in the survey results are reviewed as
      evidence of lack of validity lending support to the contrary community perception
      of low health care quality at the hospital. Suggestions are made for improvement
      of the survey instrument and procedures to insure greater validity and
      reliability.

PMID- 10915392
TI  - The use of drug formularies in managed care.
AB  - As a way of controlling the rising costs of health care, most managed care
      companies have implemented drug formularies. A drug formulary is generally
      defined as a listing of medications the health plan will cover for reimbursement.
      Some medications may need authorization from the health plan before they will be
      dispensed. This paper argues that drug formularies contain cost while causing no
      physical harm to the patient. The method of research used is descriptive. The
      paper will examine the issue from the side of the physician, the health plan and
      the patient. The research includes personal interviews, anecdotal records and
      reviews of available literature. The findings will show that patients still have
      access to a wide range of therapeutic medications and do not suffer physical harm
      as a result of a drug formulary.

PMID- 10915393
TI  - Hospital web-site marketing: analysis, issues, and trends.
AB  - As hospitals continue to incorporate web technology into their overall marketing
      and communications strategies, they face several issues which we explore in this
      paper. Hospitals' effectiveness in dealing with these issues will affect the
      benefits received from this technology. We provide an exploratory analysis of
      current hospital web sites and develop implications for future web site
      development. Likewise, recommendations based on our research are also provided.

PMID- 10915394
TI  - Increased efficacy and tolerability with losartan plus hydrochlorothiazide in
      patients with uncontrolled hypertension and therapy-related symptoms receiving
      two monotherapies.
AB  - The efficacy and tolerability of losartan 100 mg/hydrochlorothiazide (HCTZ) 25 mg
      and enalapril 10 mg/HCTZ 25 mg were compared in a double-blind, randomized trial
      in hypertensive patients inadequately controlled and experiencing side effects on
      prior therapy. Patients with moderate or severe hypertension, currently treated
      with at least two single-agent drugs (excluding angiotensin-converting enzyme
      inhibitors), with a sitting diastolic blood pressure (DBP) above 90 mm Hg, and at
      least one undesirable drug-related symptom were randomized to once-daily
      treatment with one of the combinations for 12 weeks. Losartan/HCTZ lowered
      sitting DBP from the prior therapy baseline by 13.7 mm Hg and sitting systolic
      blood pressure 19.3 mm Hg; similar reductions occurred with enalapril/HCTZ.
      Trough sitting DBP was reduced to normal levels (< 90 mm Hg) in 63% of patients
      switched to the losartan combination and in 58% of those treated with the
      enalapril combination. Each combination was associated with improved tolerability
      compared with prior therapy, although fewer patients reported each of 24
      undesirable symptoms after 12 weeks of losartan/HCTZ. The improvement from prior
      therapy in the occurrence of cough was significantly greater with losartan/HCTZ
      (P = .005). Enalapril/HCTZ, but not losartan/HCTZ, increased serum uric acid
      levels at week 12. In conclusion, the combination of losartan 100 mg/HCTZ 25 mg
      offers a beneficial therapeutic option for patients with a history of moderate to
      severe hypertension whose blood pressure is not adequately controlled or who
      exhibit side effects while on two or more single-agent antihypertensive drugs. In
      this population, the switch from prior antihypertensive therapies to once daily
      losartan 100 mg/HCTZ 25 mg improves blood pressure control and reduces side
      effects.

PMID- 10915395
TI  - Effect of two balanced salt solutions on the bioavailability of ofloxacin and
      ciprofloxacin.
AB  - Metal ions, which are present in ocular fluids, can significantly decrease the
      bioavailability of fluoroquinolones. This in vitro study investigated the
      bioavailability of ofloxacin and ciprofloxacin in the presence of two balanced
      salt solutions, BSS-Plus and AMO Endosol, commonly used as irrigants in cataract
      surgery. Minimum inhibitory concentrations (MICs) and antibiotic susceptibility
      were determined through broth dilution methods and a standard disk diffusion
      bioassay with Escherichia coli. Although neither solution affected the in vitro
      antimicrobial activity of ofloxacin, both markedly decreased that of
      ciprofloxacin. In BSS-Plus and AMO Endosol, the MICs of ciprofloxacin for several
      ocular isolates were increased, indicating decreased susceptibility to that drug;
      the activity of ciprofloxacin against E. coli was also decreased. Because the
      composition of BSS-Plus is similar to that of human aqueous humor, the clinical
      efficacy of ofloxacin may be unaffected by the ionic composition of the aqueous
      humor. In contrast, because the antimicrobial activity of ciprofloxacin was
      diminished in BSS-Plus, the clinical efficacy of this fluoroquinolone against
      deep ocular infections may not be as great as indicated by standard laboratory
      antibiotic susceptibility testing.

PMID- 10915396
TI  - Primary immunosuppression with tacrolimus in renal transplantation: a
      multicenter, open-label study.
AB  - A multicenter, prospective, open-label trial was performed to assess the efficacy
      and safety of tacrolimus for primary immunosuppression in renal transplantation.
      Twenty patients were evaluated after receiving cadaveric and living, related or
      unrelated kidney transplants and were monitored for 6 months for patient and
      graft survival, incidence of acute rejection, and incidence of adverse events.
      Tacrolimus at a final mean dose of 0.11 mg/kg per day was 100% effective in
      preventing acute rejection in this Mexican population. Treatment was associated
      with a low incidence (10%) of posttransplant diabetes mellitus.

PMID- 10915397
TI  - Tolerability and efficacy of high-dose furosemide and small-volume hypertonic
      saline solution in refractory congestive heart failure.
AB  - Thirty patients aged 65-85 years, with refractory New York Heart Association
      (NYHA) class IV congestive heart failure (CHF) were treated with an intravenous
      infusion of furosemide (250-2000 mg/d) and small-volume hypertonic saline
      solution (150 mL of 1.4-4.6% NaCl) twice a day for 6 to 12 days. A daily fluid
      oral intake of 1000 mL and previous cardiac therapy were maintained. Clinical
      signs and symptoms of CHF, such as dyspnea, edema and weakness, improved, as did
      severity of illness as defined by NYHA class. The infusion was well tolerated.
      After a 12-month follow-up, 24 patients (80%) were alive and in the NYHA class
      assigned on discharge from the hospital. This therapeutic combination is
      effective and well tolerated and should represent an innovative approach to the
      management of refractory CHF.

PMID- 10915398
TI  - Efficacy and tolerability of the lipidosterolic extract of Serenoa repens
      (Permixon) in benign prostatic hyperplasia: a double-blind comparison of two
      dosage regimens.
AB  - This 3-month double-blind, randomized, parallel-group study compared the efficacy
      and tolerability of two regimens of the lipido-sterolic extract of Serenoa repens
      (Permixon) (two 160-mg capsules once daily [OD] and one 160-mg capsule twice
      daily [BID]) in 100 outpatients with symptomatic benign prostatic hyperplasia
      (BPH). Both regimens significantly (P < .0001) reduced the International Prostate
      Symptom Score (I-PSS) mean total score from baseline; improvements achieved
      statistical significance after the first month and were maintained for the
      duration of the study. Significant (P < .05) and rapid improvements from baseline
      to the end of month 1 also occurred in I-PSS quality-of-life (QoL) scores,
      maximum and mean urinary flow rates, and residual urine volume; this benefit was
      further increased at month 3 for I-PSS total score and QoL and residual volume,
      and was maintained for maximum and mean flow rates. A highly significant decrease
      (P < .001) in residual urine was observed in both groups. No significant
      differences were noted between regimens. Clinical adverse events occurred at a
      similar incidence in both groups (BID, 24%; OD, 22%) and were deemed unrelated or
      unlikely to be related to Permixon.

PMID- 10915399
TI  - Effects of nedocromil sodium on antigen-induced conjunctivitis in guinea pigs.
AB  - We evaluated nedocromil sodium in a guinea pig model of allergic conjunctivitis.
      Ten days after the animals were passively sensitized to ovalbumin, nedocromil
      sodium (2 mg) or normal saline was instilled into the conjunctival sac, followed
      by antigen challenge with ovalbumin (100 micrograms or 300 micrograms/10 microL).
      Conjunctival hyperemia, edema, and eyelid edema were evaluated at 10 minutes and
      4 hours in the 100-microgram ovalbumin group. Eyes with nedocromil sodium
      exhibited fewer early and late clinical signs of allergic conjunctivitis than
      control eyes. Infiltrating eosinophils were counted at 24 hours in the 300
      microgram ovalbumin group. Nedocromil sodium inhibited antigen-induced eosinophil
      infiltration into the limbus, fornix, and eyelids by 77%, 66%, and 74%, compared
      with controls. Nedocromil sodium can effectively suppress early- and late-phase
      conjunctival hyperemia, conjunctival edema, eyelid edema, and eosinophil
      infiltration in the guinea pig passive-sensitization model. Nedocromil sodium may
      represent a versatile option for the treatment of allergic conjunctivitis.

PMID- 10915400
TI  - Clarithromycin suspension vs penicillin V suspension in children with
      streptococcal pharyngitis.
AB  - Clarithromycin, an advanced-generation macrolide antibiotic, has demonstrated
      excellent in vitro activity against group A beta-hemolytic streptococcus (GABHS).
      Potent activity against Streptococcus pyogenes and a favorable pharmacokinetic
      profile have made it a reasonable alternative for treatment of patients with
      streptococcal pharyngitis. The safety and efficacy of clarithromycin and
      penicillin V were compared in a randomized, investigator-blind study. Children 6
      months to 12 years of age received 5 days of clarithromycin suspension 7.5 mg/kg
      twice daily (n = 268) or 10 days of penicillin V suspension 13.3 mg/kg three
      times daily (n = 260). Patients were evaluated for signs and symptoms of
      pharyngitis, and throat swabs for culture were obtained prior to therapy, at the
      end of therapy, and at follow-up. Clarithromycin and penicillin V produced
      comparable rates of clinical success (cure + improvement) at the posttreatment
      (97% and 94%) and follow-up (81% and 82%) evaluations. The GABHS eradication
      rate, however, was significantly higher with clarithromycin (94% vs 78%, P <
      .001). Both drugs were well tolerated; gastrointestinal complaints were similar
      and mild. Resistance did not occur with the short course of clarithromycin or the
      standard regimen of penicillin V. Five days' treatment with clarithromycin was
      superior to 10 days of penicillin in eradicating S. pyogenes.

PMID- 10915401
TI  - Topical ketanserin gel for anal fissure: an open-label, prospective study.
AB  - This open-label, prospective study assessed the efficacy and safety of topical
      ketanserin gel in 63 patients with symptomatic anal fissure. The efficacy outcome
      was total clinical healing of the fissure. Topical ketanserin gel was 90%
      effective (fissure healed) and 100% safe (no adverse events) in the primary
      nonsurgical treatment of anal fissure.

PMID- 10915402
TI  - Antibiotic consumption patterns and drug leftovers in 6000 Brazilian households.
AB  - Worldwide data indicate that antibiotics are frequently used indiscriminately.
      The present study used a questionnaire in an attempt to quantify and qualify
      outpatient antibiotic consumption habits, including when the drug was used, who
      recommended it, and to what extent treatment was completed, and to question
      householders on the presence of antibiotics in their homes, including leftovers
      from previous treatments. The questionnaire was distributed to residents of 6000
      households that made up a representative sample of the Brazilian population and
      was completed by designated respondents from 4932 residences (82.2%) with or
      without field interviewer supervision. Each household reported an average of 3.7
      treatments in the previous year, with amoxicillin the most frequently used
      antibiotic in this survey (18%), regardless of socioeconomic class. Most
      treatments were recommended through medical prescription, and this source of
      antibiotic was associated with the highest rate of completed therapy (80.4%).
      Azithromycin and ciprofloxacin produced the highest rates of completed treatment
      and the lowest rates of antibiotic leftovers. Storing antibiotics at home
      increases the cost of each treatment event, reduces efficacy, and may encourage
      the emergence of resistant organisms in the community. Educational efforts must
      be redoubled to promote the rational and effective use of drugs, especially
      antibiotics.

PMID- 10915403
TI  - Early-invasive or early-conservative management of patients with unstable angina
      or non-Q-wave myocardial infarction.
AB  - The optimal therapy for non-ST-segment-elevation acute coronary syndromes is the
      subject of considerable debate: is early catheterization and revascularization
      (early-invasive strategy) or continued medical therapy unless symptoms are
      refractory (early-conservative strategy) best? Although several clinical trials
      have sought to answer this question, the methodologies they employed have been
      widely criticized, and no consensus has been reached. The new antiplatelet
      therapies have proved beneficial for primary medical management and as adjuncts
      to percutaneous interventions. It is not yet clear, however, whether use of these
      therapies will preferentially benefit one of the treatment strategies.

PMID- 10915404
TI  - Nedocromil sodium in two models of conjunctival immediate hypersensitivity.
AB  - The effects of intravenous administration of nedocromil sodium were investigated
      in active and passive models of conjunctival immediate hypersensitivity in rats.
      In the active sensitization model, animals were immunized with ovalbumin 21 days
      prior to ocular instillation of a solution containing ovalbumin. Nedocromil
      sodium administered prior to antigen challenge significantly inhibited emergence
      of conjunctival edema and erythema (P < .05) and reduced mast cell degranulation
      (P < .02). In the passive-sensitization model, the conjunctiva in one eye was
      injected with ovalbumin antiserum 48 hours prior to intravenous administration of
      ovalbumin. Nedocromil sodium administered prior to antigen challenge
      significantly and dose-dependently reduced appearance of the signs of
      conjunctivitis (P < .01) as well as vascular leakage (P < .05). These data
      indicate that intravenous nedocromil sodium is effective in animal models of
      allergic conjunctivitis and may have potential for wider therapeutic application.
      These data are also consistent with results of clinical studies in which
      nedocromil sodium relieved symptoms of allergic conjunctivitis and further
      support a role for nedocromil sodium in the prevention of allergic
      conjunctivitis.

PMID- 10915405
TI  - Stop propagating disaster myths.

PMID- 10915406
TI  - The international search and rescue response to the US Embassy bombing in Kenya:
      the medical team experience.

PMID- 10915407
TI  - Cardiovascular mortality--the hidden peril of heat waves.
AB  - OBJECTIVE: Define the mortality associated with extremely hot weather during the
      04 July through 14 July, 1993 heat wave that struck the northeastern United
      States. METHODS: DESIGN--A rapid field assessment was used to compare mortality
      occurring during the heat wave to mortality occurring during a period in which
      there was no heat wave using copies of death certificates. The findings of the
      rapid field assessment were validated, and it was determined whether increases in
      mortality occurred in other metropolitan east-coast counties also affected by the
      heat wave, by reviewing computerized mortality files. SETTING--Information was
      collected on all deaths occurring in Baltimore City, Maryland; Baltimore County,
      Maryland; Essex County, New Jersey; Newcastle County, Delaware; and Philadelphia
      County, Pennsylvania; during these specified study periods: 08-18 June
      (comparison period) and 06-16 July (heat wave study period), 1993. MAIN OUTCOME
      MEASURES--Ratios for total mortality, cause-specific mortality, and variables
      such as age, sex, race, residence, and day and place of death, that were
      available from death certificates were calculated. RESULTS: From the rapid field
      assessment, the following were observed: a 26% increase in total mortality and a
      98% increase in cardiovascular mortality associated with the heat wave in
      Philadelphia. Data from the computerized mortality files showed an increase in
      total mortality in four of five counties examined and an increase in
      cardiovascular mortality in all five counties. The risk for death for those dying
      from cardiovascular disease increased significantly for people older than 64
      years, for both sexes, and all races. CONCLUSION: As initially indicated by the
      Philadelphia Medical Examiner, there was excess mortality associated with a heat
      wave in Philadelphia. All other nearby counties examined also experienced excess
      mortality associated with the heat wave, although this excess was not recognized
      by the local health officials. The true impact of a heat wave that causes excess
      preventable mortality must be appropriately and rapidly ascertained. Using a
      national standard to certify a death as heat-related will provide the needed
      information rapidly so that public health resources can be more effectively
      allocated and mobilized to prevent further heat-related illnesses and death.

PMID- 10915408
TI  - Racial and ethnic patterns in the utilization of prehospital emergency transport
      services in the United States.
AB  - INTRODUCTION: This descriptive research used a large, urban population-based data
      set for prehospital, emergency medical transports to examine racial/ethnic
      patterns of access and utilization for several broad categories of emergency
      medical transport services. METHODS: Fire department files of approximately
      39,000 reports on service provision were used to establish rates of transport
      utilization per 1,000 population in 1990, the most recent year for which reliable
      city-level census data were available. Data were categorized by three age groups
      (< 25 years, 25-64 years, > or = 65 years), three racial/ethnic groups (non
      Hispanic whites, African-Americans, Hispanics), and gender. Transport rates were
      computed for total utilization, trauma incidents, and incidents due to medical
      conditions. Racial/ethnic rates were analyzed for each age and gender group and
      age- and gender-standardized rates were analyzed and presented in a graphical
      comparison. Statistical analyses of racial/ethnic differences were conducted
      using Tukey-type tests of multiple comparisons of proportions, with significant
      differences evaluated at the p = 0.001 level of significance. RESULTS:
      Significant differences between racial/ethnic groups in the utilization of
      emergency transport services existed for all pair-wise comparisons including
      comparisons by each of the three age groups and gender. For total utilization,
      unadjusted rates are highest for African-Americans (65.9/1,000) and lowest for
      Hispanics (25.8/1.000). Likewise, African-American rates were substantially
      higher for both gender groups and across all age groups. Categorized by gender
      and age group under age > or = 65 years, non-Hispanic whites are observed to have
      the lowest rates for both males and females under the age 65 years, while
      Hispanics have the lowest rates in the group 65 years old However, when rates are
      age- and gender-standardized, compared to African-Americans and Hispanics, rates
      for non-Hispanic whites are significantly lower for total transports and for
      trauma and medically related transports (p = 0.001). CONCLUSION: Age- and gender
      standardized rates for emergency medical transport were found to be lowest for
      non-Hispanic, whites, moderately higher for Hispanics, and substantially higher
      for African-Americans, who experienced transport rates nearly three times higher
      than were the rates for non-Hispanic whites. Further research is required to
      establish the extent to which racial/ethnic differences observed in this
      geographically restricted study reflect variations between racial/ethnic groups
      in the underlying need for services.

PMID- 10915409
TI  - Job stressors and job satisfaction in a major metropolitan public EMS service.
AB  - INTRODUCTION: Behavioral and social science research suggests that job
      satisfaction and job performance are positively correlated. It is important that
      EMS managers identify predictors of job satisfaction in order to maximize job
      performance among prehospital personnel. PURPOSE: Identify job stressors that
      predict the level of job satisfaction among prehospital personnel. METHODS: The
      study was conducted within a large, urban Emergency Medical Services (EMS)
      service performing approximately 60,000 Advanced Life Support (ALS) responses
      annually. Using focus groups and informal interviews, potential predictors of
      global job satisfaction were identified. These factors included: interactions
      with hospital nurses and physicians; on-line communications; dispatching;
      training provided by the ambulance service; relationship with supervisors and;
      standing orders as presently employed by the ambulance service. These factors
      were incorporated into a 21 item questionnaire including one item measuring
      global job satisfaction, 14 items measuring potential predictors of satisfaction,
      and seven questions exploring demographic information such as age, gender, race,
      years of experience, and years with the company. The survey was administered to
      all paramedics and Emergency Medical Technicians (EMTs) Results of the survey
      were analyzed using univariate and multivariate techniques to identify predictors
      of global job satisfaction. RESULTS: Ninety paramedics and EMT participated in
      the study, a response rate of 57.3%. Job satisfaction was cited as extremely
      satisfying by 11%, very satisfying by 29%, satisfying by 45%, and not satisfying
      by 15% of respondents. On univariate analysis, only the quality of training,
      quality of physician interaction, and career choice were associated with global
      job satisfaction. On multivariate analysis, only career choice (p = 0.005) and
      quality of physician interaction (p = 0.05) were predictive of global job
      satisfaction. CONCLUSIONS: Quality of career choice and interactions with
      physicians are predictive of global job satisfaction within this urban emergency
      medical service (EMS). Future studies should examine specific characteristics of
      the physician-paramedic interface that influence job satisfaction and attempt to
      generalize these results to other settings.

PMID- 10915410
TI  - Sensation seeking as it relates to burnout among emergency medical personnel: a
      Texas study.
AB  - INTRODUCTION: Burnout among emergency medical personnel (EMP) is suspected, but
      largely unsupported in the literature. An investigation of the phenomenon of
      burnout and factors contributing to its existence are essential steps in
      designing effective interventions. RESEARCH QUESTIONS: Three research questions
      were proposed: 1) Are EMP sensation seekers as measured by Arnett's Inventory of
      Sensation Seeking? 2) Are EMP burnt out as measured by Revicki's Work-Related
      Strain Inventory? 3) Is there a relationship between sensation seeking and
      burnout among EMP? METHODS: Emergency medical personnel attending a statewide
      conference in Texas, USA in late 1996 completed 425 survey instruments measuring
      sensation seeking and burnout as well as demographic items. Survey instruments
      were included in each registrant's conference package. Completed surveys were
      deposited anonymously in labeled receptacles throughout the statewide conference
      site. Data collection ceased at the end of the conference. RESULTS: EMP had
      significantly higher sensation-seeking total and intensity subscale scores than
      the general public. Full-time employees reported more sensation-seeking than
      volunteers or part-time employees. The younger the EMP, the greater were their
      reported sensation seeking tendencies. EMP reported more burnout in 1996 than in
      1991. The older the EMP, the lower was the reported level of burnout. EMP who
      sought counseling for a work-related event reported more burnout than those who
      did not. Paid full-time EMP reported higher burnout than did volunteers. There
      was a weak but positive correlation between sensation seeking and burnout,
      suggesting that these two dimensions may be unrelated. CONCLUSIONS: The field of
      emergency medical services attracts sensation seekers, and EMP today report more
      burnout than their counterparts did in 1991. Although EMP appear to be high in
      sensation seeking, this dimension alone does not protect them from the effects of
      burnout.

PMID- 10915411
TI  - The cost-benefit of pulse-oximeter use in the prehospital environment.
AB  - INTRODUCTION: Pulse-oximetry has proven clinical value in Emergency Departments
      and Intensive Care Units. In the prehospital environment, oxygen is given
      routinely in many situations. It was hypothesized that the use of pulse oximeters
      in the prehospital setting would provide a measurable cost-benefit by reducing
      the amount of oxygen used. METHODS: This was a prospective study conducted at 12
      ambulance stations (average transport times > 20 minutes). Standard care
      protocols and paramedic assessments were used to determine which patients
      received oxygen and the initial flow rate used. Pulse-oximetry measurements
      (SpO2) were then taken. If SpO2 fell below 92% or rose above 96% (except in
      patients with chest pain), oxygen (O2) flow rates were adjusted. Costs of oxygen
      use were calculated: volume that would have been used based on initial flow rate;
      and volume actually used based on actual flow rates and transport time. RESULTS:
      A total of 1,907 patients were recruited. Oximetry and complete data were
      obtained on 1,787 (94%). Of these, 1,329 (74%) received O2 by standard protocol:
      389 (27.5%) had the O2 flow decreased; 52 had it discontinued. Eighty-seven
      patients (6%) not requiring O2 standard protocol were hypoxemic (SpO2 < 92%) by
      oximetry, and 71 patients (5%) receiving oxygen required flow rate increases.
      Overall, O2 consumption was reduced by 26% resulting in a cost-savings of
      $0.20/patient. Prehospital pulse-oximetry allows unnecessary or excessive oxygen
      therapy to be avoided in up to 55% of patients transported by ambulance and can
      help to identify suboptimally oxygenated patients (11%). CONCLUSIONS:
      Rationalizing the O2 administration using pulse-oximetry reduced O2 consumption.
      Other health care savings likely would result from a reduced incidence of
      suboptimal oxygenation. Oxygen cost-saving justifies oximeter purchase for each
      ambulance annually where patient volume exceeds 1,750, less frequently for lower
      call volumes, or in those services where the mean transport time is less than the
      23 minute average noted in this study.

PMID- 10915413
TI  - Collinwood: an anatomy of a disaster.

PMID- 10915412
TI  - A safety assessment of diaspirin cross-linked hemoglobin (DCLHb) in the treatment
      of hemorrhagic, hypovolemic shock.
AB  - OBJECTIVE: To determine the safety and possible efficacy of diaspirin cross
      linked hemoglobin (DCLHb) in the treatment of patients in Class II-IV
      hemorrhagic, hypovolemic shock. DESIGN: Multicenter, randomized, normal saline
      controlled, dose-escalation study. SETTING: Eleven hospitals in the U.S. and
      Belgium. SUBJECTS: One hundred and thirty-nine (139) hospitalized patients with
      Class II-IV hemorrhagic, hypovolemic shock within the previous 4 hours who still
      were requiring therapy for shock. INTERVENTIONS: Beginning with the lowest dose,
      patients were randomized to receive 50, 100, or 200 mL of either 10% DCLHb or
      normal saline infused intravenously over 15 minutes. Following infusion of either
      treatment, further fluid resuscitation could be given, as necessary, to maintain
      perfusion. Vital signs, laboratory assessments, blood and fluid administration,
      complications, and adverse events were recorded at various times from the end of
      infusion through 72 hours after infusion. RESULTS: A total of 29 (13 DCLHb- and
      16 saline-treated) patients died during the study period. Adverse events were
      experienced by 61% of patients in the DCLHb group and 53% of patients in the
      saline group; serious adverse events occurred in 28% of DCLHb-treated patients
      and 30% of saline-treated patients. The incidence of prospectively defined,
      clinical complications, including renal insufficiency and renal failure, was
      similar between the treatment groups except for the occurrence of
      dysrhythmias/conduction disorders, which occurred significantly more frequently
      in the saline-treated patients than the DCLHb-treated patients (p = 0.041). At
      the highest dose level (200 mL), statistically significant between-group
      differences were observed with greater increases in serum amylase, LDH, the
      isoenzymes LD1,2,4 and 5, and CK-MB in the DCLHb group compared to the control
      group; none were of clinical significance. The volume of blood administered did
      not differ between the groups. Overall 24- and 72-hour survival rates were
      similar between treatment groups, although the hospital discharge rate was
      slightly higher in the DCLHb-treated patients (80%) compared with the saline
      treated patients (74%). CONCLUSION: Administration of 50 to 200 mL of DCLHb to
      patients in hemorrhagic, hypovolemic shock was not associated with evidence of
      end organ toxicity or significant adverse events. Further studies involving
      larger doses and, perhaps, earlier administration of DCLHb are warranted.

PMID- 10915414
TI  - Fred C. Cuny Memorial Continuing Education series: principles of disaster
      management. Lesson 6: Personnel and personnel management.
AB  - Relief operations require capable responsible staff. This lesson discusses the
      types of staff and workers required. It stresses the importance of employing
      locals and refugees in filling many of these positions, and examines the role of
      volunteers, paid personnel, and expatriates and the issues involved.

PMID- 10915415
TI  - Cidofovir: new preparation.  Of help in CMV retinitis.
AB  - (1) Cidofovir is an antiviral drug indicated for intravenous treatment of
      cytomegalovirus retinitis in patients with AIDS. (2) The evaluation file is
      limited. (3) The cidofovir dose regimen (one infusion of 5 mg/kg once a week for
      fifteen days then once every fifteen days) was determined in three comparative
      trials. (4) These trials, involving patients with relatively low risk of visual
      deterioration, showed that cidofovir slowed the progression of retinitis on
      fundoscopy but had no effect on visual acuity. (5) Cidofovir has not been
      compared with the other two antiviral drugs used by the intravenous route in the
      treatment of retinitis, i.e. ganciclovir and foscarnet. (6) Cidofovir frequently
      has adverse effects.  The most troublesome are nephrotoxicity and eye damage,
      with a possible impact on visual acuity. (7) Cidofovir is easier to administer
      (weekly infusions, then fortnightly during maintenance) than ganciclovir or
      foscarnet (daily infusions for long periods).

PMID- 10915416
TI  - Transdermal fentanyl: new preparation.  An alternative to morphine.
AB  - (1) Fentanyl, an opiate agonist, was previously available in injectable form for
      use in anaesthesia.  The new patch form is indicated for the treatment of chronic
      cancer pain. (2) The clinical assessment mainly involved non comparative trials
      showing good analgesic efficacy on chronic pain. (3) Given the long time-lag
      before the effect of fentanyl is felt, a short-acting analgesic should be given
      when the first patch is applied.  Once adequate relief has been achieved the
      patch can be used alone to treat chronic pain.  It must be replaced every three
      days. (4) Fentanyl patches have similar adverse effects to opiate agonists, i.e.
      gastrointestinal and neuropsychological disorders.  However, the adverse effects
      of morphine and fentanyl are not always identical in a given patient. (5)
      Fentanyl patches carry a risk of misuse by opiate addicts and of acute
      intoxication.

PMID- 10915417
TI  - Nevirapine: new preparation.  In second-line triple-drug anti-HIV regimens.
AB  - (1) Nevirapine is the first non nucleoside inhibitor of HIV-1 reverse
      transcriptase to be marketed in France. (2) The clinical file comprises three
      comparative double-blind trials.  One showed a better clinical benefit (in terms
      of disease progression or death) of a three-drug regimen comprising zidovudine,
      didanosine and nevirapine than with zidovudine + didanosine bitherapy.  Two
      trials focusing on laboratory criteria (viral load and the CD4+ cell count)
      showed that a three-drug regimen of zidovudine + didanosine + nevirapine was more
      effective, after 12 months of treatment, than bitherapy with zidovudine +
      nevirapine or zidovudine + didanosine. (3) Occasionally severe cutaneous
      reactions are the main adverse effects of nevirapine. (4) Nevirapine is a liver
      enzyme inducer, hence the possibility of drug interactions, especially with
      protease inhibitors of HIV; the clinical consequences are poorly known.

PMID- 10915418
TI  - Interferon beta-1A: new preparation. A short-term impact on the course of
      multiple sclerosis.
AB  - (1) Interferon beta-1a is the second interferon beta to be marketed (after
      interferon beta-1b) for the treatment of multiple sclerosis. (2) The cornerstone
      of the clinical file is a single placebo-controlled trial that showed, in the
      first two years of treatment, that interferon beta-1a slowed disease progression
      in patients with multiple sclerosis progressing through exacerbations, who were
      able to walk unaided.  The longer-term action is not known. (3) Interferon beta
      1a has not been compared with interferon beta-1b, which has no demonstrated
      action on progression of disability linked to the disease. (4) Like interferon
      beta-1b, the systemic adverse effects of interferon beta-1a are mainly a 'flu
      like syndrome and the onset of neutralising interferon antibodies, the clinical
      consequences of which are unknown.  Indirect comparison suggests that local
      tolerability at the injection site could be better with interferon beta-1a. (5)
      Treatment with interferon beta-1a is simpler than with interferon beta-1b, as the
      former can be kept at room temperature before reconstitution and is given in a
      single weekly injection instead of three.

PMID- 10915419
TI  - Valsartan: new preparation.  Just a second-line antihypertensive drug.
AB  - (1) Valsartan is a antihypertensive drug belonging to the family of angiotensin
      II receptor antagonists. (2) At a dose of 40 mg/day its antihypertensive effect
      is inconsistent. (3) At 80 mg/day its effect on blood pressure, its adverse
      effects and its contraindications (mainly pregnancy and renal artery stenosis)
      are similar to those of angiotensin-converting-enzyme (ACE) inhibitors, except
      that coughing is rarer with valsartan than with ACE inhibitors. (4) Valsartan has
      no demonstrated advantage over losartan, another angiotensin II antagonist. (5)
      Valsartan has not been shown to prevent the complications of arterial
      hypertension, and its use is therefore less well validated than that of diuretics
      and betablockers.

PMID- 10915420
TI  - Donepezil: new preparation.  Moderate efficacy in Alzheimer's disease.
AB  - (1) Donepezil is an anticholinesterase indicated for the symptomatic treatment of
      Alzheimer's disease. (2) Three comparative placebo-controlled trials are
      available, and show that the effects of donepezil are moderate and visible only
      on psychometric scales; the possible clinical benefit is unknown.  In the long
      term, donepezil only delays cognitive deterioration by a few months. (3) No
      published trials have yet compared donepezil with tacrine. (4) During clinical
      trials and the first months on the US market the adverse effect profile of
      donepezil was acceptable.  No hepatotoxicity has yet been described, although it
      is known to occur with tacrine.

PMID- 10915421
TI  - Birth defects due to topical adapalene and tretinoin.
AB  - (1) In animals, adapalene and tretinoin are teratogenic. (2) In humans, reports
      of several disturbing cases have been published after cutaneous administration.
      (3) Remember to warn women of child-bearing potential.  Inadvertent exposure
      during pregnancy necessitates special monitoring.

PMID- 10915422
TI  - Toxicity of chloroform.
AB  - (1) Chloroform is strongly absorbed by the pulmonary, oral and cutaneous routes.
      (2) It has adverse cardiac, hepatic, renal, dermatological, neurological and
      ophthalmological effects.  Deaths related to chloroform use have occurred.  In
      animals, chloroform is carcinogenic and embryotoxic. (3) Since 1997, the European
      and French medicines agencies have no longer considered chloroform to be a simple
      solvent.  Only minimal amounts are authorised in drug preparations (no more than
      0.6 mg/day).

PMID- 10915423
TI  - Hepatitis C: limits and dose regimen of interferon alfa.
AB  - (1) Hepatitis C can progress over decades, leading in some cases to cirrhosis or
      liver cancer. (2) The only treatment currently approved for preventing long-term
      complications of hepatitis C is interferon alfa (2a or 2b) at 3 MU 3 times a week
      for 12 months.  It is recommended only for patients with chronic active hepatitis
      C. (3) The assessment of interferon alfa in clinical trials is based on surrogate
      end points (transaminase levels, histopathological changes, clearance of
      viraemia), and the results sometimes conflict. (4) There is no firm evidence that
      interferon alfa prevents cirrhosis. (5) Treatment with interferon alfa can be
      stopped after 3 months when patients fail to respond. (6) Thyroid disorders are
      the most important adverse effect of interferon alfa.

PMID- 10915425
TI  - Wall Street comes to Washington: analysts' perspectives on the changing health
      care system.
AB  - Market forces and recent policy changes are rocking the health care system,
      according to a panel of Wall Street analysts who track health care companies. In
      the fourth annual Wall Street roundtable convened by the Center for Studying
      Health System Change (HSC), analysts discussed the reasons behind improved health
      plan profitability, providers' struggles to maintain--let alone increase--market
      power, trends in consolidation and the dramatic impact of federal legislation on
      all sectors of the industry. This Issue Brief reports on how the analysts see
      these and other forces playing out in the future.

PMID- 10915424
TI  - Fracture prevention in elderly women: treatment of osteoporosis is one approach,
      together with physical exercise and fall prevention.
AB  - (1) Osteoporosis is one of several recognized causes of bone weakness in elderly
      women, and accounts for the high incidence of fractures.  Hip fracture carries
      the highest rates of morbidity and mortality. (2) Bone density measurement in a
      given woman is not predictive of her individual risk of fracture.  None of the
      recommendations we examined propose routine screening for osteoporosis by bone
      density measurement in all postmenopausal women. (3) Women at risk should be
      identified, so that they can benefit from detection and prevention.  Detection is
      mainly based on clinical evidence. (4) Whatever the age and period of life,
      prevention of osteoporotic fractures in women is based on adequate supply of
      calcium (at least 1 g/day, mainly in the diet) and vitamin D, and on regular
      physical exercise and fall prevention. (5) Oestrogen therapy is the first-line
      drug-based prevention of osteoporotic fractures, despite worries about possible
      carcinogenicity. (6) Routine hormone replacement therapy for all women, starting
      at menopause, is not recommended.  The decision should be made individually. (7)
      Before starting treatment, patients should be informed of the need for long-term
      compliance. (8) Consensus statements recommend hormone replacement therapy as
      secondary prevention for women having already had osteoporotic fractures, and as
      primary prevention for women at risk.

PMID- 10915426
TI  - Neurological surgery.

PMID- 10915427
TI  - Total hip replacement.

PMID- 10915428
TI  - Who declines employer-sponsored health insurance and is uninsured?
AB  - Twenty percent of all uninsured persons are offered health insurance by their
      employer or a family member's employer but choose not to enroll in the offered
      plan(s).  Most persons who do not "take up" or enroll in available employer
      sponsored coverage cite cost as the main reason why.  This Issue Brief, based on
      two surveys conducted as part of the Center for Studying Health System Change's
      (HSC) Community Tracking Study, presents new findings on who declines employer
      sponsored coverage and is uninsured as a result.  Given the importance of cost in
      an individual's decision whether to enroll in employer-sponsored coverage, policy
      makers need to consider ways to address the problem identified by this study: low
      take-up rates among lower-income workers.

PMID- 10915429
TI  - Transesophageal echocardiography.

PMID- 10915430
TI  - Pathologists' assistants.

PMID- 10915432
TI  - Pediatrics.

PMID- 10915431
TI  - Health care law.

PMID- 10915433
TI  - Mechanical ventilation.

PMID- 10915434
TI  - Tracking health care costs: long-predicted upturn appears.
AB  - After three years of anticipation, health care cost trends have taken an upward
      turn.  In employment-based insurance, premium increases for 1999 were in the 5
      percent range, up from 3 percent for 1998.  The rate of increase in underlying
      costs of private insurance--lagged by one year--also rose by approximately 2
      percentage points.  Many had expected a sharper upturn in premium increases than
      underlying cost increases.  This would have heralded a turn in the insurance
      underwriting cycle, which has not yet occurred. This Issue Brief tracks the rate
      of growth of health care costs and the experience with premiums for employment
      based health insurance and discusses the impact of these trends on consumers.

PMID- 10915435
TI  - Endovascular grafts.

PMID- 10915436
TI  - Oral and maxillofacial surgery.

PMID- 10915437
TI  - Organ allocation and the states: can the states restrict broader organ sharing?

PMID- 10915438
TI  - The scope of care expected of primary care physicians: is it greater than it
      should be?
AB  - The United States has long relied on specialist physicians more heavily than
      other countries, and some policy experts have repeatedly recommended that the
      share and role of primary care physicians (PCPs) be increased as a way of
      providing cost-effective care.  The growth of managed care, changing practice
      arrangements and new medical technology are forces that may be increasing the
      role of PCPs.  This Issue Brief reports findings published in the New England
      Journal of Medicine showing that many physicians believe the scope of care
      provided by PCPs without referral to specialists is increasing.  Moreover, almost
      a quarter of PCPs report that the scope of care they are expected to provide is
      greater than it should be.  The likelihood of PCPs' concern is related to
      specific managed care techniques, practice size and specialty, among other
      factors.

PMID- 10915440
TI  - Internal medicine.

PMID- 10915439
TI  - Gamma knife radiosurgery.

PMID- 10915441
TI  - Insolvency and challenges of regulating providers that bear risk.
AB  - Risk contracting and capitation are two widely used financial mechanisms that
      give incentives to health care providers to control costs. Risk-bearing
      arrangements have failed in a number of communities, however. This has shaken
      local markets, disrupting consumers' access to health care services and
      triggering losses for physicians and hospitals. It also has raised questions
      about the adequacy of related regulatory oversight, which holds important
      implications for local and national policy makers. This Issue Brief provides case
      studies of failed risk-contracting arrangements in two of the 12 communities that
      the Center for Studying Health System Change (HSC) tracks intensively--Northern
      New Jersey and Orange County, Calif.--and examines implications for policy
      makers.

PMID- 10915442
TI  - Prostate cryosurgery.

PMID- 10915443
TI  - Nuclear medicine.

PMID- 10915444
TI  - Adults mourning suicide: self-reported concerns about bereavement, needs for
      assistance, and help-seeking behavior.
AB  - This study empirically characterized the experiences of 227 adult next-of-kin as
      they mourned suicides that had occurred in New York City during 1997.  Next-of
      kin reported psychosocial problems including family difficulties, comorbid
      stressors, psychiatric symptomatology, and unresolved bereavement. Professional
      intervention was the most frequently reported need and the most frequently
      reported type of desired help.  In terms of actual receipt of assistance,
      participants reported having received help from families, friends, and
      communities as well as from professionals. Although some next-of-kin had not
      sought help because they felt able to cope without assistance, others encounted
      barriers to receiving desired help.  These findings warrant increased and
      sustained community outreach to this population.  Recommendations include public
      education regarding de-stigmatization of suicide and the needs of the suicidally
      bereaved, enhancement of internal and external coping supports, facilitation of
      access to both professional and community help, and better coordinated and more
      culturally appropriate services.

PMID- 10915445
TI  - The loss response list: a tool for measuring adolescent grief responses.
AB  - Single adolescent girls aged 13-19 years participated in pilot (n = 40) and
      follow-up (n = 164) studies to develop the reliability and validity of the Loss
      Response List (LRL).  The LRL measures physical, emotional, social, and cognitive
      grief responses by comparing groups based on pregnancy status (never pregnant,
      pregnant, perinatal loss, and perinatal loss and pregnant). The pilot study
      revealed significant results on emotional, social, and cognitive grief responses
      between the perinatal loss and no-perinatal loss groups. Follow-up study results
      indicated significant differences between the perinatal loss group and the other
      groups on grief subscales. Significant differences also occurred between
      perinatal loss and never pregnant groups on depression.  The LRL should be useful
      in gathering information about adolescent grief responses, including perinatal
      loss.

PMID- 10915446
TI  - Grief and school communities: the impact of social context, a comparison between
      Australia and England.
AB  - This study investigated whether secondary schools in Australia and England had a
      plan to manage traumatic incidents and to identify practice and programs related
      to grief education and suicide intervention and prevention.  Ninety-four percent
      of an Australian sample of 145 schools had such plans in place, compared with
      only 15% of an English sample of 200 schools.  Differing policy contexts for
      grief, and the lack of teacher training and minimal education about grief in
      England, were discussed as possible explanations for the variation.  It is
      concluded that a more proactive approach will only be achieved when there is
      system-level policy and training support, as well as school and individual
      teacher recognition of their potential contribution to young people's well being.

PMID- 10915447
TI  - Bereavement services in acute care settings.
AB  - Families of acute care patients who die while receiving care face loss and grief
      in unfamiliar institutional environments.  Informal bereavement assistance may
      occur in acute care settings, but formally organized service and planned follow
      up work with bereaved family members is less common.  A literature review
      revealed little discussion of acute care-related bereavement services.  The
      detrimental effects of long-term, unresolved grief, however, are well documented.
      Bereavement services help to reduce immediate physical and emotional distress
      while ameliorating long-term morbidity associated with unresolved grief.  They
      may also reduce eventual costs for services and discomfort of illness by reducing
      the likelihood of stress-related illnesses occurring among survivors. Health care
      workers such as social workers, psychiatrists, chaplains, and nurses, who are
      familiar with the psychosocial needs of families and the structure and staffing
      of these settings, are well-positioned to organize assistance for those
      experiencing sudden loss.  Developing a formal bereavement program in acute care
      settings involves description of the need, presenting the rationale for the
      service, identification of program elements, and determination of resource needs.
      Even in situations in which full services may not be possible, the provision of
      basic assessment and referral services will be beneficial to survivors while
      offering the institution several benefits.

PMID- 10915448
TI  - Parents' perceptions of their children's death concept.
AB  - To examine the differences between parents' and nonparents' beliefs regarding the
      concept of death in children, 352 individuals answered a demographic survey. 
      Questions concerning beliefs about the age at which children develop the concept
      of the irreversibility of death were included on the survey.  Parents believed
      that the concept is developed at an earlier age than did nonparents, and also
      believed that the concept is developed at an earlier age than has been revealed
      by most research.

PMID- 10915449
TI  - Do HMOs make a difference?
AB  - The growth of managed care has prompted questions about the effects of health
      maintenance organizations (HMOs) on consumers. This Issue Brief reports the
      results from a large national study of the privately insured population. No
      detectable difference was found between HMOs and other types of insurance in the
      use of three costly services--inpatient care, emergency room use and surgeries-
      and differences in reports of unmet need or delayed care are negligible.
      Differences for other measures pose a trade-off for consumers: HMOs provide more
      primary and preventive services and lower financial barriers to care, but they
      provide less specialist care and raise administrative barriers to care. In
      addition, patients in HMOs report less satisfaction, less trust in physicians and
      lower ratings of physician visits. These findings have implications for the
      current policy debate about managed care.

PMID- 10915450
TI  - Exploring integrated health care approaches.

PMID- 10915451
TI  - Reproductive misconception: why cloning is not just another assisted reproductive
      technology.

PMID- 10915452
TI  - The dilemmas of incrementalism: logical and political constraints in the design
      of health insurance reforms.
AB  - Health care reform became a premier issue on the U.S. policy agenda in the 1990s.
      While the comprehensive proposal put forth by President Clinton failed, states
      and the federal government successfully pursued a variety of lesser initiatives. 
      This article focuses on a set of reforms intended to make private health
      insurance more accessible and affordable to individuals and workers in small
      firms.  It outlines the key arguments made by experts to justify stronger
      regulation of health insurance and the options and difficult tradeoffs that must
      be considered in policy design.  It then examines the scope and strength of
      legislation adopted by 45 states and the federal government from 1990 to 1996. 
      The substantial variation in state policies demonstrates that even though
      insurance market reform was the one issue that commanded nearly universal support
      in the health care debate, few design features were universally accepted by those
      who crafted the reforms.  The article concludes by assessing the pattern of state
      and federal action.  The reforms represent some progress on nominal access to
      insurance but little progress on the affordability of insurance for individuals
      and small groups.  Few of the reforms present a serious challenge to existing
      practices and interests of the insurance industry.  This pattern of policy design
      reflects the logical and political constraints of incrementalism.  In a system
      where insurance coverage is voluntary, changes to increase access for one group
      tend to increase costs and thereby decrease access for another segment of the
      population.  In addition, because incremental reforms will not attract sustained
      attention and support from the general public, it is politically difficult to
      impose substantial new regulation on a powerful industry.

PMID- 10915453
TI  - Parents' health, health care utilization, and health behaviors following the
      violent deaths of their 12- to 28-year-old children: a prospective longitudinal
      analysis.
AB  - Health status, health care utilization, and health behaviors of parents bereaved
      by the violent deaths of their adolescent and young adult children were examined
      4, 12, and 24 months later.  Participants were 261 bereaved parents (171 mothers,
      90 fathers).  About 20% of the parents reported "poor" physical health during the
      early bereavement period compared with 16% of Americans the same age.  Over time,
      mothers' health improved whereas fathers' health deteriorated.  Fathers in poor
      health compared with fathers in good health are 15 times more likely to report
      emotional distress and 4.6 times more likely to report trauma symptoms.  Mothers
      in poor health compared with mothers in good health are 11 times more likely to
      report emotional distress and 3 times more likely to report trauma symptoms.
      Mothers' reports of physician visits and medication use were higher than
      fathers', however, mothers' rates for both decreased significantly over time
      whereas fathers' rates remained constant. Over 70% of the mothers and nearly 60%
      of the fathers practiced 2 or more health protective behaviors over time--a
      finding significantly associated with fewer stress-related illnesses, days absent
      from work, and non-productivity at work.  Implications for the findings are
      discussed.

PMID- 10915454
TI  - Elderly adults' preferences for life-sustaining treatments: the role of
      impairment, prognosis, and pain.
AB  - Elderly adults' preferences for life-sustaining treatment are known to vary by
      type of medical condition and treatment.  Less is known about how treatment
      preferences vary based on underlying health dimensions, such as the nature of the
      impairment, prognostic information, and the experience of pain.  Fifty elderly
      adults stated preferences for 4 life-sustaining treatments in response to 4 pairs
      of health state scenarios.  Overall, life-sustaining treatments were preferred
      less in response to (a) cognitive versus physical impairment, (b) when the
      prognosis described no chance versus a very slight chance of
      recovery/improvement, and (c) if pain was present.  These findings have
      implications for the way in which preferences for life-sustaining treatments are
      recorded in advance directives.  Historically, advance directives have been
      limited by overly broad or overly specific statements about treatment
      preferences.  Recording underlying health dimensions that guide treatment
      decisions may allow decision makers to generalize and apply patient preferences
      to novel health conditions.

PMID- 10915455
TI  - Long-term impact of sudden infant death: a 12- to 15-year follow-up.
AB  - To understand parents' subjective feelings, experiences, and understanding
      connected to the loss of a child over time, the authors chose semi-structured, in
      depth interviews as the method of examination in a study of 26 parents who lost a
      child to sudden infant death syndrome (SIDS) between 1981 and 1984.  In addition,
      parents were asked to complete different inventories to compare their present
      responses (1996) with their responses to the same inventories in 1981-1984.  Most
      parents still viewed the death of their child as affecting their daily life in
      important ways.  Inventory data show that gender differences have diminished 12
      15 years after the loss, and few parents are psychologically at risk in 1996. 
      The study clearly shows the benefit of method triangulation in providing a total
      picture of the parent's experiences.

PMID- 10915456
TI  - A Medicare prescription drug benefit.
AB  - Even though almost two-thirds of Medicare beneficiaries have some coverage for
      outpatient prescription drugs, pharmaceuticals are a major part of their out-of
      pocket expenses and threaten the financial security of growing numbers of
      beneficiaries.  Because pharmaceuticals are an integral part of modern health
      care, some have proposed adding a drug benefit to Medicare.  Such proposals pose
      difficult questions of design, cost, and administration.  A drug benefit could
      add between 7 and 13 percent per year to Medicare costs over the next decade.  If
      such a benefit were added to Medicare, policymakers would have to decide who
      should bear these costs and whether subsidies should be provided to help lower
      income beneficiaries pay the portion of the costs borne by participants.

PMID- 10915457
TI  - Should higher income beneficiaries pay more for Medicare?
AB  - As Medicare cost increase, policymakers are searching for equitable ways to
      secure the program's financial base.  Proposals that would require higher-income
      Medicare beneficiaries to pay a higher proportion of the program's costs are
      designed to increase beneficiaries' contribution without placing an unacceptable
      financial burden on those least able to afford it.  Designing and implementing
      such a policy involves difficult tradeoffs in terms of revenue gains, burden on
      beneficiaries, and political support for Medicare over the long term.

PMID- 10915458
TI  - Individualizing Medicare.
AB  - Despite the enactment of significant changes to the Medicare program in 1997,
      Medicare's Hospital Insurance trust fund is projected to be exhausted just as the
      baby boom enters retirement.  To address Medicare's financial difficulties, a
      number of reform proposals have been offered, including several to individualize
      Medicare financing and benefits.  These proposals would attempt to increase
      Medicare revenues and reduce Medicare expenditures by having individuals bear
      risk--investment market risk before retirement and insurance market risk after
      retirement.  Many fundamental aspects of these proposals have yet to be worked
      out, including how to guarantee a baseline level of saving for health insurance
      after retirement, how retirees might finance unanticipated health insurance price
      increases after retirement, the potential implications for Medicaid of inadequate
      individual saving, and whether the administrative cost of making the system fair
      and adequate ultimately would eliminate any rate-of-return advantages from
      allowing workers to invest their Medicare contributions in corporate stocks and
      bonds.

PMID- 10915459
TI  - The economic status of the elderly.
AB  - The economic status of the elderly improved greatly since the 1960s. This is true
      in terms of poverty rates, real cash income and broader income measures that
      include in-kind benefits.  Yet, many older Americans remain at risk of economic
      deprivation, especially the less educated, those living alone, and the oldest
      old.  Most elderly Americans rely heavily on Social Security and Medicare for
      their economic well-being.

PMID- 10915460
TI  - The financing needs of a restructured Medicare program.  National Academy of
      Social Insurance study panel on Medicare financing.
AB  - Through the Bipartisan Commission on the Future of Medicare and other efforts,
      policy makers have begun to redesign Medicare to meet long-term challenges that
      include an aging population, rising per capita health care costs, and an
      inadequate benefit package.  However, no proposal as of yet fully addresses
      Medicare's financing needs.  Without any changes, revenues from taxpayers to the
      program would need to more than double in 2030 over 1998 levels in order to
      support current benefits.  Expanding Medicare to cover prescription drugs or to
      address other inadequacies in benefits would make Medicare's financing needs even
      greater.  The Breaux/Thomas premium support proposal to the Bipartisan Commission
      would have required about 80 percent more in revenues from taxpayers in 2030 than
      Medicare needed in 1998.  Although it is important to ensure that Medicare
      operate as efficiently as possible, this analysis suggests that any comprehensive
      discussion about Medicare's future must include the need for new revenues.

PMID- 10915461
TI  - Internal analgesic, antipyretic, and antirheumatic drug products for over-the
      counter human use; final rule for professional labeling of aspirin, buffered
      aspirin, and aspirin in combination with antacid drug products; technical
      amendments.  Department of Health and Human Services (HHS), Public Health Service
      (PHS), Food and Drug Administration (FDA).  Final rule; technical amendments.
AB  - The Food and Drug Administration (FDA) is amending the regulations for internal
      analgesic, antipyretic, and antirheumatic drug products for over-the-counter
      (OTC) use to correct inadvertent errors and to clarify the labeling for over-the
      counter drug products written for health professionals.

PMID- 10915462
TI  - Medicare program; revision to accrual basis of accounting policy. Department of
      Health and Human Services (HHS), Health Care Financing Administration (HCFA). 
      Final rule.
AB  - Medicare policy provides that payroll taxes that a provider becomes obligated to
      remit to governmental agencies are included in allowable costs only in the cost
      reporting period in which payment (upon which the payroll taxes are based) is
      actually made to an employee.  Therefore, for payroll accrued in 1 year but not
      paid until the next year, the associated payroll taxes are not an allowable cost
      until the next year.  This final rule provides for an exception when payment
      would be made to the employee in the current year but for the fact that regularly
      scheduled payment date is after the end of the year.  In that case, the rule
      requires allowance in the current year of accrued taxes on payroll that is
      accrued through the end of the year but not paid until the beginning of the next
      year, thus allowing accrued taxes on end-of-the year payroll in the same year
      that the accrual of the payroll itself is allowed.  The effect of this rule is
      not on the allowability of cost but rather only on the timing of payment; that
      is, the cost of payroll taxes on end-of-the-year payroll is allowable in the
      current period rather than in the following period.

PMID- 10915463
TI  - HCFA to implement new MDS correction policy.

PMID- 10915464
TI  - AHCA seeks additional ambulance exclusions from SNF financial responsibility.

PMID- 10915465
TI  - Life in limbo: the transplant wars. States, Congress fight over life-saving
      organs.

PMID- 10915466
TI  - Allergy epidemic. Everyone seems to be sneezing, and our lifestyle may be the
      culprit. But help is on the way.

PMID- 10915467
TI  - Doing battle with dust. Choose the right targets and don't overdo it.

PMID- 10915468
TI  - DNA from the dead may offer little to the living.

PMID- 10915469
TI  - A new and wily germ. Scientists are alarmed at drug-resistant infections.

PMID- 10915470
TI  - Beyond the pale: sunless tanning no longer leaves you looking like a yam.

PMID- 10915471
TI  - Don't rush the workouts if you're a new mother.

PMID- 10915472
TI  - Pharmacological effect of nitroprusside on platelet aggregation.
AB  - Adequate platelet function and numbers are critical for postcardiopulmonary
      bypass patients. Endogenous and pharmacological sources of nitric oxide (NO) are
      known inhibitors of platelet aggregation. Sodium nitroprusside (SNP), used
      clinically to control blood pressure, is an inorganic source of NO. Our long-term
      goal is to determine if SNP infusion in the venous return line of the
      cardiopulmonary bypass system would preserve platelet numbers and function
      without affecting systemic vascular resistance. Our first requirement to
      accomplish this goal was to develop an assay that would detect the SNP effect on
      platelet aggregation. We, therefore, tested the hypothesis that clinical
      concentrations of SNP would inhibit platelet aggregation. We quantified platelet
      aggregation with the Medtronic Hepcon HMS whole blood aggregometer. Normal
      heparinized human blood was treated with 0.625 to 12.5 nM platelet activating
      factor (PAF), 0.25 to 5.0 microM epinephrine, or 0.20 to 10 microM adenosine 5'
      diphosphate (ADP) to stimulate platelet aggregation. SNP was added at 10(-5) M to
      determine its affect on PAF, epinephrine, and ADP stimulated platelet
      aggregation. The results demonstrated that PAF-stimulated platelet aggregation
      was significantly inhibited with SNP (10(-5) M) to 82% (p < .05) of control and
      epinephrine and ADP mediated aggregation were not significantly affected. In
      conclusion, at clinically relevant concentrations SNP inhibits platelet
      aggregation by PAF but not with ADP or epinephrine.

PMID- 10915473
TI  - Removal of hepatocarcinoma cells from blood via cell washing and filtration
      techniques.
AB  - Utilization of autotransfusion during tumor resection remains controversial due
      to viability of carcinoma cells remaining in collected blood. The purpose of this
      study was to evaluate autotransfusion techniques combined with leukocyte
      depleting filters (LDF) for removal of hepatocarcinoma cells from
      autotransfusate. An in vitro model was created by contaminating expired human
      erythrocytes with cultured hepatocarcinoma (HEP G2) cells. Autotransfusion
      devices evaluated were Cobe BRAT2, Sorin STAT-P, and Fresenius CATS.
      Autotransfusate collected from varying processing conditions were filtered using
      the Pall Leukoguard RS or Pall Purecell RCQ LDF. Carcinoma concentrations were
      quantified via Coulter Counter technology. The CATS exhibited higher
      concentrations of cancer cells in the autotransfusate prior to washing, a 449%
      increase. This was significantly higher than either the BRAT2 or STAT-P, 350% and
      315% respectively. Post washing HEP G2 concentrations in the BRAT2 were
      significantly higher than the STAT-P and CATS. Doubled wash volumes removed more
      HEP G2 cells in all trials, reaching statistical significance only in the CATS.
      LDF resulted in a significant 75% reduction of HEP G2 cells, with no difference
      between filters. While combination use of autotransfusion devices and leukocyte
      depleting filters did result in a product with concentrated hematocrit, no
      technique removed all hepatocarcinoma cells.

PMID- 10915474
TI  - Plasmapheresis during cardiopulmonary bypass: a proposed treatment for
      presensitized cardiac transplantation patients.
AB  - Potential thoracic organ transplantation recipients who have positive cytotoxic
      antibody screens as quantified panel reactive antibodies (PRA) are at risk for
      immediate or long-term immunologic events that may affect the donor organ. The
      patient population at risk includes those who are supported with cardiac assist
      devices, multiparous women, and individuals receiving numerous homologous blood
      products. We treated three highly positive PRA patients with intraoperative
      plasmapheresis coupled to the cardiopulmonary bypass system to remove sufficient
      cytotoxic antibody. Upon the availability of donor hearts of an unknown HLA type,
      intraoperative plasmapheresis was performed using a Cobe Spectra Plasmapheresis
      system coupled to a Terumo CXSX18 oxygenator system. Three plasma volume
      exchanges of fresh frozen plasma (FFP) were performed while the patients were on
      cardiopulmonary bypass. One to one and one-half plasma volume exchange
      plasmaphereses were performed with a declining schedule for the next 30 days post
      transplantation in combination with aggressive B-cell specific immunosuppressive
      therapy. The three patients are NYHA functional class I and free of rejection at
      6 months post-transplantation. In conclusion, intraoperative plasmapheresis is
      effective and safe for the patient who would not be otherwise transplanted
      because of markedly elevated PRAs.

PMID- 10915475
TI  - 5-year incidence of thrombocytosis and the effect on heparin dose response and
      heparin requirements.
AB  - Thrombocytosis has been shown to be associated with heparin resistance. Contact
      activation of platelets results in release of Platelet Factor 4 from alpha
      granules present in the platelet cytoplasm. Platelet Factor 4 is a cationic
      substance that neutralizes heparin. This could result in inadequate
      heparinization during cardiopulmonary bypass (CPB). Inability to adequately
      anticoagulate patients with thrombocytosis could result in a poor clinical
      outcome. A retrospective review of pump records from 1991 to 1996 was used to
      assess the frequency of thrombocytosis, describe the demographic characteristics
      of patients with thrombocytosis, and determine the effects on patient heparin
      dose response (HDR) and additional heparin requirements. A platelet count of
      400,000/mm3 was chosen as a cut-off for thrombocytosis. Of the 3281 patients
      undergoing CPB during this time period, a total of 571 patients were included in
      this review: 99 had high platelet counts. The over-all prevalence of
      thrombocytosis during this time period was 3.0%. Patients with thrombocytosis
      tended to be younger (p = .02), have lower preoperative HCT (p < .001), and weigh
      less (p < .001). These patients had lower post-heparin loading dose ACTs, lower
      HDR, required more additional heparin to reach an ACT of 480 sec before CPB, and
      required more heparin on CPB to maintain the ACT > 480 sec (p < .05). Multiple
      linear regression was performed and concluded that age, use of NTG and heparin
      drip preoperatively, and platelet count were significant predictors of the
      heparin dose response. Use of plasmapheresis to remove platelet-rich plasma (PRP)
      before CPB was performed in 22 patients, six of whom had high platelet counts. In
      these patients, removal of PRP resulted in no difference in the amount of
      additional heparin required pre-CPB to reach an ACT of 480 sec. (p = NS)
      Additional studies are needed to determine whether use of plasmapheresis is a
      cost-effective and clinically useful option in patients with thrombocytosis.

PMID- 10915476
TI  - Effects on C3 and CH50 levels during and following extracorporeal whole body
      hyperthermia.
AB  - Cardiopulmonary bypass can affect inflammatory reactions and evoke the
      "postperfusion syndrome," manifested as multiple organ dysfunction in the
      recovery period. This syndrome is generated by the activation of complement,
      macrophages, neutrophils, and inflammatory cytokines. Following the use of
      hypothermia during cardiac procedures, active hyperthermic rewarming is used to
      reestablish body temperature. Complement levels and their interactions have been
      investigated during and following hypothermia. Hyperthermia is being used
      clinically; however, the effect of markedly elevated temperatures on complement
      is unknown and, therefore, needs to be investigated. A pilot canine study was
      designed to begin to explore what role hyperthermia may play on complement levels
      during and following extracorporeal whole body hyperthermia. Five dogs were
      heated to a core temperature of approximately 42 degrees C, held at this elevated
      temperature for 90 minutes, then cooled to normothermia. A decline in C3 levels
      at the end of warming with further declines through day 4 post treatment was
      observed. CH50 levels mimicked the C3 level decline; however, there was a trend
      for rebounding by day 4. The findings involving complement factors following
      hyperthermia signify that this increase in temperature causes a decrease in both
      C3 and CH50 levels.

PMID- 10915477
TI  - Hematological effects of a low-prime neonatal cardiopulmonary bypass circuit
      utilizing vacuum-assisted venous return in the porcine model.
AB  - Limiting hemodilution in neonates is difficult when extracorporeal circuits
      require priming volumes that are 2 to 3 times the blood volume of the newborn
      patient. This extreme hemodilution contributes to the development of significant
      postbypass coagulation disturbances. The purpose of this project was to design a
      low-prime neonatal bypass circuit and evaluate the coagulation status after
      reduced hemodilution. The null hypothesis stated there is no significant
      difference in the measured coagulation parameters between the low-prime circuit
      and the standard high-prime circuit. Four neonatal piglets (2-4 kg) were divided
      into two groups and placed on cardiopulmonary bypass using either a low- (200 ml)
      or high-prime (500 ml) circuit. Both groups were cooled to 20 degrees C, and,
      following cardioplegic arrest, underwent circulatory arrest for 20 minutes. The
      low-prime circuit used vacuum-assisted venous drainage, which permitted the
      circuit to be at the patient level. The high-prime circuit required fresh washed
      donor red blood cells to maintain the hematocrit in the desired range of 15-20%.
      The platelet count on bypass decreased by 60 +/- 1.0% in the low-prime group
      versus 79.6 +/- 0.1% in the high-prime group. Following bypass, the platelet
      count was reduced by 38.3 +/- 14.3% in the low-prime versus 60.2 +/- 2.6% in the
      high-prime group. During rewarming, the mean heparinase activated clotting time
      (ACT) increased 5.1% above baseline in the low-prime group and 53.5% above
      baseline in the high-prime group. Mean plasma-free hemoglobin levels increased
      40.4 mg/dl in the low-prime group versus 62.1 mg/dl in the high-prime group
      during bypass. This laboratory evaluation of a low-prime neonatal circuit
      demonstrates that coagulation disturbances often present in neonates can be
      reduced with the use of a low-prime circuit.

PMID- 10915478
TI  - Systemic inflammation induced by cardiopulmonary bypass: a review of pathogenesis
      and treatment.
AB  - The acute respiratory distress syndrome (ARDS) is a severe alteration in lung
      structure and function that develops secondary to a traumatic stimulus. When ARDS
      develops following cardiopulmonary bypass (CPB) it is know as postpump syndrome
      (PPS). ARDS can be caused by a single massive insult ("hit"); however, sequential
      minor insults ("hits") are more common clinically. The concept of multiple
      sequential insults causing ARDS has been termed the "two-hit" model of ARDS. The
      purpose of this article is to summarize our studies testing the hypothesis that
      PPS is caused by multiple sequential insults. To confirm our hypothesis, we
      developed a porcine model of "two-hit" PPS. Our model was composed of sequential
      benign insults, with CPB as the "first hit" and low dose of endotoxin as the
      "second-hit." It is our hypothesis that the mechanism of PPS is CPB-induced
      priming of polymorphonuclear leukocytes (PMNs) ("first-hit") with subsequent PMN
      activation by a second insult ("second-hit") such as endotoxin. Our model
      confirms this clinically relevant postulate, and we provide strategies to disrupt
      the inflammatory cascade leading to PPS.

PMID- 10915479
TI  - The emergency use of recombinant hirudin in cardiopulmonary bypass.
AB  - The most common anticoagulant used for cardiopulmonary bypass is heparin. An
      alternate form of anticoagulant therapy is needed for patients who have immune
      mediated heparin-associated thrombocytopenia (HIT). Thrombocytopenia causes
      bleeding and may lead to serious arterial and venous thrombosis. HIT or heparin
      induced thrombocytopenia with thrombosis type II (HITT) are both described as
      adverse reactions to heparin. They are diagnosed with a platelet count less than
      a 100,000/mcl for 2 consecutive days. HITT, the severe form, is characterized
      with the thrombocytopenia in combination with thromboembolic complications, such
      as strokes, myocardial infarctions, and limb ischemia. Two cases are presented in
      which r-hirudin was used for anticoagulation for aortocoronary bypass surgery and
      mitral valve replacement. The activated partial prothrombin time (aPTT) was used
      to monitor coagulation. In the first case, the aPTT was maintained greater than
      100 seconds, and at the termination of cardiopulmonary bypass, some clot was
      noted in the cardiopulmonary bypass circuit. In the second case, a longer
      cardiopulmonary bypass run was anticipated, the hirudin bolus and infusion rate
      were increased, and the aPTT was maintained at greater than 200 sec. Adequate
      coagulation resulted, and, at the end of bypass, no clot was noted. These case
      studies seem to suggest a higher dosage of r-hirudin may be required for the use
      of cardiopulmonary bypass and a need to maintain aPTT values greater than 200 sec
      to help monitor anticoagulation.

PMID- 10915481
TI  - Modular robotic assembly of small devices.
AB  - The use of robots for the automatic assembly of devices of up to 100 x 100 x 100
      mm is relatively uncommon today. Insufficient return on investment and the long
      lead times that are required have been limiting factors. Innovations in vision
      technology have led to the development of robotic assembly systems that employ
      flexible part-feeding. The benefits of these systems are described, which suggest
      that better ratios of price to productivity and deployment times are now
      achievable.

PMID- 10915480
TI  - Surface modification of stents for improving biocompatibility.
AB  - Much headway is being made in the quest to improve biocompatibility and reduce
      restenosis related to the use of stents. This article reviews the research data
      involving stent coatings and surface treatments techniques. It also describes
      recent work in surface modification of metallic stents and covalent coupling of
      drugs that employs a novel bonding process.

PMID- 10915482
TI  - Materials comment: PVC, why all the fuss?

PMID- 10915483
TI  - Tissue engineering research: the engineer's role.
AB  - Tissue engineering holds the promise of revolutionary advances for health care.
      Academic, clinical and industrial efforts are increasingly directed towards the
      development of autogenic substitutes to restore, maintain, or improve tissue and
      organ functions. This article summarizes the role of the engineer in the
      multidisciplinary environment of tissue engineering research.

PMID- 10915484
TI  - Medical device directive: preparing for the amendments.
AB  - Article 21 of the In Vitro Diagnostic (IVD) Directive (98/79/EC) contains several
      important amendments to the Medical Device (MD) Directive (93/42/EEC). This is
      generally well known. However, the amendments are not always being kept in mind
      when discussing the requirements of the MD Directive. This article reviews the
      more important amendments and suggests that it is time to begin planning for
      them. The new definition of IVD products is also provided.

PMID- 10915486
TI  - The UK industry.

PMID- 10915485
TI  - Business comment total value management.

PMID- 10915487
TI  - Sophisticated medical devices as local drug-delivery systems.
AB  - The sustained release of antimicrobial substances from catheters, endoprostheses,
      wound-dressings and arterial grafts may be prudent for the prevention of device
      associated infections. The release of heparin, synthetic prostacycline, hirudin
      and anti-inflammatory dexamethasone and related compounds from stent coatings may
      further reduce the risk of thrombosis, intimal hyperplasia and the requirement
      for long-term anticoagulation treatments. The delivery of cytokines and growth
      factors from wound dressings and bone grafts may accelerate wound healing and
      implant integration.

PMID- 10915488
TI  - Software validation for medical devices and in vitro diagnostics.

PMID- 10915489
TI  - Rethinking the status quo.
AB  - Even when a medical device appears to have been refined, tested and used
      extensively there is invariably scope for further improvement. Input from outside
      the relevant specialist field can encourage a rethink of the status quo. The
      resultant enhancements can benefit the doctor and patient as well as offer the
      manufacturer a marketing opportunity to increase sales and profitability. This
      design story describes innovation in intrauterine contraceptive device
      technology.

PMID- 10915490
TI  - Thermoplastic vulcanizates: new materials of choice.
AB  - Increasingly, thermoplastic vulcanizates of ethylene propylene diene monomer
      rubber-polypropylene are being specified for medical applications. This article
      describes their properties and advantages over thermoset rubbers and other
      conventional medical elastomeric materials.

PMID- 10915491
TI  - A strategy for company improvement.
AB  - Strategies based on the kaizen methodology are designed to continuously improve
      company performance without the need for large capital investments. This article
      looks at how one company used simple kaizen principles to its advantage,
      achieving 67% increase in productivity and 10% reduction in the standard cost of
      product.

PMID- 10915493
TI  - Medical device reporting: another final rule, Part I.
AB  - The history of the United States (US) Medical Device Reporting (MDR) Regulation
      is long and complicated. This has made compliance with the requirements an
      especially challenging exercise. The publication of a new regulation clarifies
      some outstanding reporting issues, but not all. Part I of this article includes a
      chronology of MDR regulations and discusses some requirements that should be of
      particular interest to non-US companies. Part II will discuss the contents of the
      new MDR regulation.

PMID- 10915495
TI  - Are price clubs a good deal for patients and physicians?

PMID- 10915496
TI  - United health group: no prior approval required.

PMID- 10915492
TI  - The Irish medical device industry.

PMID- 10915494
TI  - Chips with everything.
AB  - Silicon chips are taken for granted. They are, however, the heart of the majority
      of electronic products. Integrated electronic circuits of this sort increase the
      functionality of many devices, enabling them to do more, while making them
      smaller. Application-specific integrated circuit technology is becoming cheaper
      to purchase and can enhance performance and reliability. Manufacturers are urged
      to take advantage of the benefits it offers.

PMID- 10915498
TI  - Gainsharing struck down by office of inspector general.

PMID- 10915497
TI  - 16 marketing tips to enhance patient satisfaction.

PMID- 10915499
TI  - Electronic prescribing.

PMID- 10915500
TI  - Progress in patients' rights.

PMID- 10915501
TI  - Last year in brief and major issues of the new millennium.

PMID- 10915502
TI  - Trends in the consumer price index.

PMID- 10915503
TI  - Improving efficiency in office practices.
AB  - Office practices are very busy places. However, a large degree of inefficiency
      and wasted effort is embedded in all of that activity. Improving efficiency
      enhances an office's ability to provide care in a more organized, comfortable
      environment for clinicians, staff, and patients alike. It improves access to care
      and allows more time to be spent on important clinical issues. Improving
      efficiency improves an office's work capacity without adding resources and,
      therefore, improves its financial performance as well.

PMID- 10915504
TI  - Enhancing the medical practice: consorting with the emergency department.
AB  - In 1994, the Department of Emergency Medicine at Loma Linda University Medical
      Center (LLUMC) set out to implement a comprehensive emergency department (ED)
      model: a model that headed in the opposite direction of popularized solutions of
      which the objective is to keep patients out of the ED. This model increases the
      number of services offered. It triages patients within its walls to an area cost
      effective for the patient's acuity and allows patients to immediately move to a
      higher level of care if the provider sees the need. Three years of data have
      determined the comprehensive ED model to be an effective, patient-focused
      alternative to the "demand management" methods. Low-acuity patients at LLUMC are
      treated in less costly areas. The high-tech-laden "MainED" is better utilized
      because of a 25% increase in complex patients since 1993. In addition, the
      comprehensive ED model appears to be a valuable resource that enhances the
      outpatient medical practice.

PMID- 10915505
TI  - Practice compliance programs: reducing therapeutic misadventures and adverse
      outcomes.
AB  - Contemporary medical group practice administrators navigate a complex world of
      challenges, questions, and ambiguous circumstances. Adverse outcomes and
      therapeutic misadventures have significant implications within this world.
      Practice compliance programs must be developed to reduce risk and liability. As
      with any negative behavior, event or disruptive action, therapeutic misadventure
      is easily identified; however, determining a strategy to correct physician
      behavior, attitude, and action is sensitive and difficult, requiring
      administrative skill, tact, and patience. This article provides corrective action
      strategies that can be applied to any therapeutic misadventure encountered in a
      typical medical group practice. Three categories are identified: problematic
      behavior, problematic practice patterns, and physician impairment. Measures to
      correct and alter physician behavior and actions are also described.

PMID- 10915506
TI  - Setting practice fees.

PMID- 10915507
TI  - E-mail: a realistic conduit for patient-doctor communications?
AB  - This article explores the potential of E-mail as a medium of patient-physician
      communication. It introduces control tactics that physicians can consider to
      increase the efficiency of the medium. These include pre-qualifying the patients
      receiving the physician's E-mail address, establishing a code for high-risk
      patients, responding to E-mail only during "down time," using response templates,
      off-loading standard questions, establishing a quota, and establishing user
      expectations. The author suggests that if physicians develop a discipline around
      handling E-mail, they can increase their effectiveness by developing closer ties
      with patients without sacrificing extra time.

PMID- 10915508
TI  - Next generation software systems provide tools for handling complexity of billing
      codes.
AB  - Medical practice staff members, intent on assuring accurate and prompt
      reimbursement by an increasing number of payers for services rendered to the
      practice's patients, face what often feels like an insurmountable challenge. Ever
      changing and differing reimbursement rules create a frustrating environment in
      which it is difficult, if not impossible, to comply with payers' requirements.
      This article provides an overview of a new generation of automated systems that
      offers physicians the ability to submit bills that more precisely comply with
      payers' expectations. It describes how claims editing software systems work and
      capabilities staff should consider before choosing a system.

PMID- 10915509
TI  - Reducing needlestick injuries.

PMID- 10915510
TI  - Is hospital peer review evidence admissible?

PMID- 10915511
TI  - Protect yourself from fraud and abuse.

PMID- 10915512
TI  - Medical care in the U.S.--who is paying for it?

PMID- 10915514
TI  - Evaluation of patient waiting times at an academic ophthalmology clinic.
AB  - Two hundred thirty-six patient visits to a major university's ophthalmology
      clinic were studied to determine patient waiting time. The waiting time was
      studied as a function of attending physician and appointment time. Patient
      arrival behavior was also documented. Recommendations regarding strategies to
      reduce waiting times were developed based on the data. The recommendations
      include: redistributing patient appointments to less busy times of the day;
      educating patients regarding the importance of punctuality; and creating a
      realistic patient appointment schedule. Awareness of the importance of waiting
      time to the health care consumer is of particular significance for the health
      care provider. The study allows analysis of waiting times in order to target
      problem areas and provides a benchmark for evaluation of waiting time reduction
      efforts. These results could be applicable to most clinical settings with varying
      mixes of patients.

PMID- 10915513
TI  - Earnings and practice pattern differences between male and female physicians.

PMID- 10915515
TI  - PSOs--an opportunity or figment of the imagination?
AB  - This article explores whether Provider-Sponsored Organizations (PSOs) offer
      providers a tangible opportunity. It describes Crozer-Keystone's participation as
      a PSO in HCFA's Medicare Choices Demonstration Project. This organization is an
      integrated system in suburban Philadelphia. Although the financial results to
      date have not been encouraging, opportunities exist for developing partnerships
      with physicians and patients.

PMID- 10915516
TI  - Why physicians are often disappointed with their practice administrators and
      managers.
AB  - This article provides a close look at why physicians often are disappointed with
      the practice administrator or manager they have hired or promoted. Reasons
      include: the wrong person was hired, such as one without the necessary
      qualifications and know-how, or the right person was hired, but wasn't given the
      authority to do the job. The article also provides practical tips on how to avoid
      mis-hires, how to evaluate the practice's managerial needs, and general
      differences between types of managers.

PMID- 10915517
TI  - Computerized patient records: current and future opportunities.
AB  - Although computerized patient record (CPR) technology holds tangible promise for
      improvements in the quality of patient care, its penetration into physician
      practices has been slow at best. This article describes the operational and
      quality of care benefits of CPR implementation and the barriers to
      implementation. These include technology limitations, cultural factors, lack of
      standards, downtime fears, security and privacy concerns, and the lack of
      alignment of economic incentives. The article also provides non-radical
      approaches (i.e., simpler and cheaper) ways to harness technology to improve
      office efficiencies and patient care.

PMID- 10915518
TI  - Physician autonomy in the managed care era: the physician-citizen or subject?
AB  - Until recently, medicine was one of the few areas in which an individual could
      practice a profession as a citizen member of the organization. However, in the
      recent overhauling of medical organizations in search of cost efficiency,
      physicians have moved from self-governing organizations with the rights of
      citizen participation to autocratic, centrally controlled organizations with
      little for physicians to do but provide high-quality manual labor. The principles
      of prosperity and choice espoused in The Federalist Papers are governance
      principles that can re-establish citizenship in medical groups.

PMID- 10915519
TI  - Will ERISA be the death knell for managed care?

PMID- 10915520
TI  - The real drug war. Beware, drug-makers. With senior citizens struggling to afford
      their prescriptions, soaring pill prices are turning into an explosive issue.

PMID- 10915522
TI  - Mind expansion: inside the teenage brain.

PMID- 10915521
TI  - Unhealthy habits. How well are teens taking care of themselves? Here's a report
      card on some of their choices.

PMID- 10915523
TI  - Fad diets: all protein, no proof.

PMID- 10915524
TI  - Is Monsanto's biotech worth less than a hill of beans? Main Street has shown
      little interest in the fight over bioengineered crops. But the international
      furor hit Monsanto's stock like a hailstorm.

PMID- 10915525
TI  - The voice of reason in the global food fight. Rockefeller Foundation chief Gordon
      Conway has emerged as the one thought leader neither side can ignore in the high
      stakes biofoods war--and the best hope for an outcome all six billion of us can
      live with.

PMID- 10915526
TI  - What the heck is Healtheon?

PMID- 10915527
TI  - Can gene therapy cure this child? The money is short and the science
      controversial, but a lot more than business rides on a biotech startup's
      survival.

PMID- 10915528
TI  - Stephen Ramirez: recipient of the 2000 Robert F. Allen Symbol of H.O.P.E. Award.

PMID- 10915529
TI  - Health and productivity management: emerging opportunities for health promotion
      professionals for the 21st century.
AB  - The authors recognize the emergence of health and productivity management as an
      important stage in the evolution of workplace health promotion and describe how
      health promotion professionals should take the lead in redirecting their
      employers' efforts to work together.

PMID- 10915530
TI  - Health and productivity management: the concept, impact, and opportunity:
      commentary to Goetzel and Ozminkowski.
AB  - The author describes a model linking health, productivity and profit, why
      productivity is so important to business, and the potential impact productivity
      enhancement can have on health promotion.

PMID- 10915531
TI  - Impact of a worksite behavioral skills intervention.
AB  - Sixty-four male and female sedentary employees were randomly assigned to an
      intervention group or control group to determine the effects of behavioral skill
      training on adoption and maintenance of exercise. Both received a 9-month
      membership at a local fitness facility. The control group received a 12-week
      semistructured course, which included a facility orientation and three meetings
      with a personal trainer. The intervention group received a 12-week behavioral
      skills course and were encouraged to participate in a 12-week semistructured
      exercise course followed by a 3-month problem-solving support intervention. Both
      groups improved their daily energy expenditure, the amount of moderate and
      vigorous activity they performed, and their strength and flexibility. The study
      sample was too small to show substantial differences between the intervention and
      control group. Changes in mediator variables were mixed.

PMID- 10915532
TI  - How do children's eating patterns and food choices change over time? Results from
      a cohort study.
AB  - PURPOSE: The purpose of this study was to investigate the change in eating
      patterns and food choices in a cohort of students as they moved from the third to
      the eighth grade. DESIGN: Dietary behaviors and food choices were abstracted from
      24-hour recalls and compared across grade levels. SETTING: The setting for the
      study was elementary and junior high schools. SUBJECTS: The subjects were a
      cohort of 291 students from Minnesota. MEASURES: Individual 24-hour dietary
      recalls from a cohort of students were collected in the third, fifth and eighth
      grades. RESULTS: As students moved from elementary to junior high and middle
      school, their consumption of breakfast, fruits, vegetables, and milk decreased.
      Soft drink consumption increased. In the third grade, nearly 99% of the cohort
      reported eating breakfast; by the eighth grade, 85% reported eating breakfast.
      Fruit consumption fell by 41% between the third and the eighth grades while
      vegetable consumption fell by 25%. The proportion of beverage coming from soft
      drinks more than tripled between the third and the eighth grades with concomitant
      reductions in milk and fruit juice consumption. CONCLUSIONS: Family, school, and
      community-wide efforts are needed to promote healthful eating patterns and food
      choices among adolescents. Our research indicates that nutrition education is
      needed in the elementary and middle school years. In addition, we need to work on
      improving teens' social and physical environments to encourage and facilitate
      their choice of healthy foods.

PMID- 10915533
TI  - The relationship between youth tobacco control enforcement and crime rates in a
      midwestern county.
AB  - The crime rate in 29 counties was compared with the level of enforcement of laws
      restricting youth purchases. There was a linear relationship between crime rate
      and enforcement. Communities with the highest enforcement policies had the lowest
      crime rates.

PMID- 10915534
TI  - School-based programs for obesity prevention: what do adolescents recommend?
AB  - Twenty-five focus groups conducted with 203 adolescent boys and girls from junior
      high and high schools in St. Paul, Minnesota, showed that students want weight
      control programs that are fun, interactive, accessible, convenient, low in cost,
      sensitive to the needs of adolescents, include multiple physical activity
      options, and are offered to all students, regardless of their weight.

PMID- 10915535
TI  - Work-family spillover and health during midlife: is managing conflict everything?
AB  - PURPOSE: To examine the association between multiple dimensions of work-family
      spillover, and physical and mental health among working midlife adults. DESIGN:
      Cross-sectional analyses of self-reported data. SETTING: The National Survey of
      Midlife Development in the United States (MIDUS), 1995. SUBJECTS: Employed adults
      aged 35-65 years (n = 1547) who participated in the telephone interview and
      returned the mail-back questionnaires of the MIDUS (overall response rate of
      60.8%). MEASURES: Independent variables included negative spillover from work to
      family, positive spillover from work to family, negative spillover from family to
      work, positive spillover from family to work. Self-rated physical health, chronic
      conditions, obesity, self-rated mental health, negative psychological well-being,
      and positive psychological well-being were outcomes. RESULTS: Independent of
      negative spillover between work and family, more positive spillover from work to
      family was associated with better physical health (odds ratio [OR] = 1.17, p < or
      = .05) and mental health (OR = 1.28, p < or = .01). More positive spillover from
      family to work was associated with less chronic conditions (OR = .85, p < or =
      .05), less negative well-being (OR = .67, p < or = .001), as well as better
      mental health (OR = 1.45, p < or = .01) and more positive well-being (OR 1.76, p
      < or = 001). CONCLUSIONS: Health promotion or employment programs and policies
      may need to focus on minimizing negative spillover between work and family and
      promoting positive spillover between work and family.

PMID- 10915536
TI  - The ecological approach in tobacco-control practice: health promotion
      practitioner characteristics related to using the ecological approach.
AB  - PURPOSE: To identify cognitive factors and personal characteristics related to
      the integration of the ecological approach in the everyday practice of health
      promotion practitioners. DESIGN: Sociodemographic, cognitive, and behavior data
      were collected using a cross-sectional mail survey. SETTING: Information was
      collected from regional public health organizations (n = 129) in the 10 Canadian
      provinces. SUBJECTS: Health promotion practitioners involved in tobacco-control
      programming for youth (n = 524) comprised of 81% women with a mean age of 39
      years. MEASURES: Attempts to integrate ecological strategies (i.e.,
      interpersonal, organizational, and policy change) into tobacco-control practice
      were based on three self-report items. Six scales assessed knowledge, values, and
      normative beliefs about the ecological approach as well as perceived need for,
      effectiveness of, and competency regarding using the ecological approach.
      RESULTS: The survey response rate was 80%. Stepwise discriminant analyses
      revealed four predictors (p < .001) contributing to the function solution
      concerning practitioner attempts to target the interpersonal environment:
      perceived competency, training discipline, years doing health promotion, and
      gender. Three predictors (p < .001) contributed to each of the function solutions
      concerning practitioner attempts to target the organizational environment
      (perceived competency, perceived effectiveness, and normative beliefs) and
      practitioner attempts at policy change (perceived competency, knowledge, and
      normative beliefs). CONCLUSIONS: Tobacco-control practitioners who perceive
      themselves as having the skills to develop and/or implement interventions
      targeting a person's environment are more likely to target the environment for
      change.

PMID- 10915538
TI  - Intraclass correlation for measures from a worksite health promotion study:
      estimates, correlates, and applications.

PMID- 10915537
TI  - Health behavior research: the quality of the evidence base.
AB  - All 1210 manuscripts published in the 12 most prestigious health promotion
      research journals in 1994 were reviewed and coded based on stage of research and
      setting. Of the total, 34% were nonresearch articles, 35% were health-behavior
      research, and 31% were related to innovation, diffusion, and
      institutionalization. Of the 469 health behavior research articles, 57% were
      observation studies, 11% were methods development, 19% were intervention studies,
      1% were meta-analyses, and 13% addressed diffusion and institutionalization. Half
      (46) of the intervention studies had randomized controlled designs. Studies were
      conducted in nonspecific community settings (206), health care settings (88),
      schools (75), specific community settings (53), workplaces (32), and universities
      (11).

PMID- 10915539
TI  - Shortage of qualified breast imagers could lead to crisis.

PMID- 10915540
TI  - Echo-planar MRI allows study of fast-changing physiologic processes.

PMID- 10915541
TI  - Spiral CT scanners promise bonanza of clinical uses.

PMID- 10915542
TI  - Could coronary calcium screening prevent this?

PMID- 10915543
TI  - Internal IT support crucial to success in filmless department.

PMID- 10915544
TI  - Integrating 3-D into PACS: pitfalls and solutions.

PMID- 10915545
TI  - Latex allergy: a laboratory view.

PMID- 10915547
TI  - Improving emergency cardiac care with a STAT, near-patient blood analyzer.

PMID- 10915546
TI  - A portable flow-through system for enzyme immunoassays.

PMID- 10915548
TI  - Financial benefits of integrating robotics into an academic medical center core
      laboratory.

PMID- 10915549
TI  - Choosing a proper laboratory procedure to identify heavy drinking in the new
      millennium.

PMID- 10915550
TI  - Kinetic Isotope Effects and Stereochemical Studies on a Ribonuclease Model:
      Hydrolysis Reactions of Uridine 3'-Nitrophenyl Phosphate.
AB  - The reactions of a ribonuclease model substrate, the compound uridine-3'-p
      nitrophenyl phosphate, have been examined using heavy-atom isotope effects and
      stereochemical analysis. The cyclization of this compound is subject to catalysis
      by general base (by imidazole buffer), specific base (by carbonate buffer), and
      by acid. All three reactions proceed by the same mechanistic sequence, via
      cyclization to cUMP, which is stable under basic conditions but which is rapidly
      hydrolyzed to a mixture of 2'- and 3'-UMP under acid conditions. The isotope
      effects indicate that the specific base-catalyzed reaction exhibits an earlier
      transition state with respect to bond cleavage to the leaving group compared to
      the general base-catalyzed reaction. Stereochemical analysis indicates that both
      of the base-catalyzed reactions proceed with the same stereochemical outcome. It
      is concluded that the difference in the nucleophile in the two base-catalyzed
      reactions results in a difference in the transition state structure but both
      reactions are most likely concerted, with no phosphorane intermediate. The (15)N
      isotope effects were also measured for the reaction of the substrate with
      ribonuclease A. The results indicate that considerably less negative charge
      develops on the leaving group in the transition state than for the general base
      catalyzed reaction in solution. Copyright 2000 Academic Press.

PMID- 10915551
TI  - Evidence for a 1,2 Shift of a Hydrogen Atom in a Radical Intermediate of the
      Methylmalonyl-CoA Mutase Reaction.
AB  - An excellent substrate of methylmalonyl-CoA mutase, methylmalonyl-carba-(dethia)
      coenzyme A (methylmalonyl-CH(2)-CoA), was synthesized by a chemoenzymatic method
      and its alpha-proton was exchanged with deuterium by long-term incubation in
      deuterium oxide at pH 6.9. After addition of highly purified epimerase-free
      methylmalonyl-CoA mutase the enzymatic rearrangement was monitored by 1H NMR
      spectroscopy. Already in the initial phases of the reaction only 72% of the
      produced succinyl-CH(2)-CoA was monodeuterated, while unlabeled and geminally
      dideuterated species, 14% of each, were also formed. After the addition of more
      enzyme the equilibrium (methylmalonyl-CoA:succinyl-CoA = 1:20) was quickly
      established, while the proportion of unlabeled succinyl-CH(2)-CoA rose to 30% and
      the geminally dideuterated species were slowly transformed to vicinally
      dideuterated ones. After 19 h of incubation the ratio of the unlabeled,
      monodeuterated, and dideuterated species was roughly 1:1:1 while no appreciable
      deuterium incorporation from the solvent occurred. The unexpected
      disproportionation of deuterium can be best explained by a 1,2 shift of a
      hydrogen atom in the succinyl-CH(2)-CoA radical intermediate competing with the
      hydrogen transfer from 5'-deoxyadenosine. A precedence for such a hydrogen shift
      in a radical was previously observed only in the mass spectrometer and was
      supported by ab initio calculations. Copyright 2000 Academic Press.

PMID- 10915552
TI  - Carbonyl J Derivatives: A New Class of HIV-1 Integrase Inhibitors.
AB  - Integration of a DNA copy of the HIV-1 genome is required for viral replication
      and pathogenicity, and this highly specific molecular process is mediated by the
      virus-encoded integrase protein. The requirement for integration, combined with
      the lack of a known analogous process in mammalian cells, makes integrase an
      attractive target for therapeutic inhibitors of HIV-1 replication. While many
      reports of HIV-1 IN inhibitors exist, no such compounds have yet emerged to treat
      HIV-1 infection. As such, new classes of integrase inhibitors are needed. We have
      combined molecular modeling and combinatorial chemistry to identify and develop a
      new class of HIV-1 integrase inhibitors, the Carbonyl J [N,N'-bis(2-(5-hydroxy-7
      naphthalenesulfonic acid)urea] derivatives. This new class includes a number of
      compounds with sub-micromolar IC(50) values for inhibiting purified HIV-1
      integrase in vitro. Herein we describe the chemical characteristics that are
      important for integrase inhibition and cell toxicity within the Carbonyl J
      derivatives. Copyright 2000 Academic Press.

PMID- 10915553
TI  - Different Activities of 5-Hydroxy-dUMP and 5-Hydroxymethyl-dUMP in Thymidylate
      Synthase-Catalyzed Reaction in View of Molecular Modeling and Structural Studies.
AB  - In order to explain different activities shown by 5-hydroxy-dUMP (substrate) and
      its close analogue 5-hydroxymethyl-dUMP (slow-binding inhibitor) in the reaction
      catalyzed by thymidylate synthase, studies have been undertaken involving (i) ab
      initio RHF simulations, (ii) comparative analysis of crystallographic structures
      available from CSD, and (iii) QSAR analysis of experimental results describing
      thymidylate synthase interaction with various 5-substituted dUMP analogues.
      Assuming substrate activity of 5-hydroxy-dUMP to be associated with proton
      release from the C(5) hydroxyl in the enzyme-catalyzed reaction, acidities of 5
      hydroxy and 5-hydroxymethyl substituents in dUMP molecule were compared. The
      results indicate the 5-hydroxyl deprotonation to be easier and supported by
      resonance electronic effect, pointing to a probable mechanism of different
      activities of the two dUMP analogues in thymidylate synthase reaction. The
      possibility is discussed that 5-mercapto-dUMP and 5-hydroseleno-dUMP, previously
      assumed to be inhibitors, could be also substrates for thymidylate synthase, as
      the 5-mercaptyl and 5-hydroselenidyl appear to be deprotonated even more easily
      than the 5-hydroxyl. Copyright 2000 Academic Press.

PMID- 10915554
TI  - A Mechanistic Study of the Dihydroflavin Reductive Cleavage of the Dihydroflavin
      Tetrahydronaphthalene Epoxide Adducts.
AB  - Dihydroflavins are facile reducing agents and potent nucleophiles. The
      dihydroflavin nucleophilic reactivity, as measured by the rate of covalent flavin
      adduct formation with tetrahydronaphthalene epoxides, is comparable to that of
      the thiolate anion (Y. T. Lee and J. F. Fisher (1993) J. Org. Chem. 58, 3712). In
      these reactions there appears subsequent to the nucleophilic cleavage of the
      epoxide by the dihydroflavin the product corresponding to formal hydride
      reduction product (at the benzylic carbon) of these epoxides. Thus the reaction
      of (+/-)-1a,2,3, 7b-tetrahydro-(1aalpha,2alpha,3beta,7balpha)-naphth[1,2
      b]oxirene-2,3-diol (1), (+/-)-1a,2,3,7b-tetrahydro-(1aalpha,2beta,3alpha,7balpha)
      naphth[1,2-b]oxirene-2,3-diol (2), and (+/-)-1a,2,3,7b-tetrahydro
      (1aalpha,7balpha)-naphth[1,2-b]oxirene (3) in 9:1 (v/v) aqueous Tris buffer
      dioxane, at both acidic and neutral pH, with FMNH(2) and 1,5-dihydrolumiflavin
      (LFH(2)) gave (following covalent flavin-epoxide adduct formation) the products
      having a methylene group at the benzylic position. The reduction product yield
      was proportional to the yield of the N(5) flavin-epoxide adduct intermediate, and
      the rate of the reaction was proportional to the dihydroflavin concentration.
      These observations are consistent with these reduction products resulting from
      bimolecular reaction between the dihydroflavin-epoxide adduct and a second
      molecule of dihydroflavin. Copyright 2000 Academic Press.

PMID- 10915555
TI  - Review Article Coenzyme-B(12)-Dependent Glutamate Mutase.
AB  - Adenosylcobalamin (coenzyme B12)-dependent glutamate mutase catalyzes a most
      unusual carbon skeleton rearrangement involving the isomerization of l-glutamate
      to L-threo-methylaspartate, a reaction that is without precedent in organic
      chemistry. This reaction proceeds through a mechanism involving free radical
      intermediates that are initiated by homolysis of the cobalt-carbon bond of the
      coenzyme. The enzyme serves as a paradigm for adenosylcobalamin-dependent
      catalysis and, more generally, provides insights into how enzymes generate and
      control reactive free radical species. This review describes how recent studies
      on the mechanism and structure of glutamate mutase have contributed to our
      understanding of adenosylcobalamin-mediated catalysis. Copyright 2000 Academic
      Press.

PMID- 10915556
TI  - Promotion of activated human B cell apoptosis and inhibition of Ig production by
      soluble CD95 ligand: CD95-based downregulation of Ig production need not
      culminate in activated B cell death.
AB  - CD95/CD95L interactions are vital to normal lymphoid homeostasis and in the
      protection against autoimmunity. To directly assess the effects of CD95L on
      activated B cell survival and Ig responses, purified human peripheral blood B
      cells, activated in vitro with SAC + rIL2, were incubated with a soluble CD95L
      fusion protein (fp) and assayed for apoptosis and IgG/IgM production. CD95L fp
      reproducibly increased apoptosis of these activated B cells and inhibited their
      Ig production. However, CD95L fp-mediated effects on activated B cell survival
      could be uncoupled from those on Ig production in that a soluble CD40L fp was
      incapable of reversing CD95L fp-mediated downregulation of Ig responses despite
      inhibiting CD95L fp-mediated apoptosis. Moreover, despite the specific caspase-8
      inhibitor z-IETD-fmk substantially protecting transformed CL-01 B cells from
      CD95L fp-mediated apoptosis and permitting their ongoing proliferation, caspase-8
      inhibition had no protective effects on CD95L fp-mediated inhibition of
      constitutive IgM production by CL-01 B cells. Collectively, these results point
      to a CD95-based downregulatory pathway in activated B cells that need not
      necessarily culminate in their death.

PMID- 10915557
TI  - Heat-shocked A20 lymphoma cells fail to induce degranulation of cytotoxic T
      lymphocytes: possible mechanism of resistance.
AB  - A20 lymphoma cells were subjected to heat shock for 2 h at 42 and 43 +/- 0.1
      degrees C and then evaluated at 37 degrees C for sensitivity to lysis by intact
      allo-specific cytotoxic T lymphocytes (CTLs), perforin-containing granules
      isolated from CTLs, and Fas-mediated apoptosis. Heat shock at 42 degrees C caused
      little change in sensitivity of the lymphoma cell line to lysis by intact CTLs or
      their isolated cytotoxic granules, but caused increased sensitivity to Fas
      mediated apoptosis. However, A20 cells shocked at 43 degrees C declined
      significantly in sensitivity to lysis by intact CTLs, while remaining very
      sensitive to perforin granules and to Fas-mediated apoptosis. Expression of the
      inducible heat shock protein was observed in A20 cells incubated at 43 degrees C,
      but not in those incubated at 42 degrees C, suggesting a role for heat shock
      proteins. Furthermore, A20 cells shocked at 43 degrees C did not provoke
      degranulation and secretion of granzymes by antigen-specific CTLs, although
      formation of CTL-target conjugates and levels of MHC class I molecules remained
      unchanged. These observations demonstrate that hyperthermia or febrile conditions
      may reduce susceptibility of target cells to CTL attack due to failure of antigen
      presentation and the inability of CTLs to recognize heat stressed targets, thus
      enabling targets to escape CTL attack.

PMID- 10915558
TI  - LFA-3 plasmid DNA enhances Ag-specific humoral- and cellular-mediated protective
      immunity against herpes simplex virus-2 in vivo: involvement of CD4+ T cells in
      protection.
AB  - Adhesion molecules are important for cell trafficking and delivery of secondary
      signals for stimulation of T cells and antigen-presenting cells (APCs) in a
      variety of immune and inflammatory responses. Adhesion molecules lymphocyte
      function-associated antigen (LFA)-1 and CD2 on T cells recognize intercellular
      adhesion molecule (ICAM)-1 and LFA-3 on APCs, respectively. Recent studies have
      suggested that these molecules might play a regulatory role in antigen-specific
      immune responses. To investigate specific roles of adhesion molecules in immune
      induction we coimmunized LFA-3 and ICAM-1 cDNAs with a gD plasmid vaccine and
      then analyzed immune modulatory effects and protection against lethal herpes
      simplex virus (HSV)-2 challenge. We observed that gD-specific IgG production was
      enhanced by LFA-3 coinjection. However, little change in IgG production was
      observed by ICAM-1 coinjection. Furthermore, both Th1 and Th2 IgG isotype
      production was driven by LFA-3. LFA-3 also enhanced Th cell proliferative
      responses and production of interleukin (IL)-2, interferon-gamma, IL-4, and IL-10
      from splenocytes. In contrast, ICAM-1 showed slightly increasing effects on T
      cell proliferation responses and cytokine production. beta-Chemokine production
      (RANTES, MIP-1alpha, and MCP-1) was also influenced by LFA-3 or ICAM-1. When
      animals were challenged with a lethal dose of HSV-2, LFA-3-coimmunized animals
      exhibited an enhanced survival rate, as compared to animals given ICAM-1 or gD
      DNA vaccine alone. This enhanced protection appears to be mediated by CD4+ T
      cells, as determined by in vitro and in vivo T-cell subset deletion. These
      studies demonstrate that adhesion molecule LFA-3 can play an important role in
      generating protective antigen-specific immunity in the HSV model system through
      increased induction of CD4+ Th1 T-cell subset.

PMID- 10915559
TI  - Role of cAMP-dependent pathway in eosinophil apoptosis and survival.
AB  - The survival and apoptosis of eosinophils is of pivotal importance for
      controlling allergic diseases such as asthma and rhinitis. In this study we have
      investigated the role for cAMP in regulating eosinophil survival and apoptosis in
      the absence of eosinophil-active cytokines. The treatment with dibutyryl cyclic
      AMP (dbcAMP) increased eosinophil survival with a concomitant decrease of
      apoptosis in a dose-dependent manner. The pretreatment with a protein kinase A
      (PKA) inhibitor blocked the effects of dbcAMP on survival and apoptosis of
      eosinophils. The catalytic subunit of PKA was translocated to nucleus in parallel
      with a robust increase of intracellular cAMP levels upon exposure to dbcAMP but
      not IL-5, suggesting the separation of PKA activation from the IL-5-induced
      suppression of eosinophil apoptosis. When eosinophils were treated with
      pharmacological inhibitors of protein kinases prior to exposure to dbcAMP or IL
      5, only the mitogen-activating protein kinase (MAPK) inhibitor, PD098059, was
      partly able to block dbcAMP-induced augmentation of eosinophil viability, whereas
      both Janus kinase 2 and MAPK inhibitors effectively interrupted the IL-5-induced
      prolongation of eosinophil survival. The effects of dbcAMP and these protein
      kinase inhibitors on eosinophil apoptosis were confirmed by morphologic analysis.
      We propose that a cAMP-dependent pathway may constitute an important component
      for regulating eosinophil survival/apoptosisand that cAMP may inhibit eosinophil
      apoptosis through the activation of PKA and of subsequent MAPK in part.

PMID- 10915560
TI  - Shear stress affects migration behavior of polymorphonuclear cells arrested on
      endothelium.
AB  - Polymorphonuclear cell (PMN) transmigration across the TNF-alpha-stimulated
      endothelial cell (HUVEC) monolayer in the presence of shear flow was monitored
      with time-lapse videotapes. More than half of the PMN that arrested on HUVEC
      transmigrated through endothelial cell junctions within the following 15 min. The
      kinetics of transmigration was significantly faster than that of PMN placed under
      static conditions. Once PMN crept into the subendothelial space, they showed
      random migration beneath the HUVEC monolayer. PMN that did not transmigrate moved
      on the apical surface of HUVEC in the direction of flow downstream. Anti-beta1
      integrin mAb (4B4) and RGD peptide inhibited the transmigration more effectively
      than anti-beta2 integrin mAb (TS1/18) and almost totally abrogated
      transmigration. When HUVEC were cultured on fibronectin or laminin, the
      transmigration was significantly inhibited by anti-alpha5 or alpha6 integrin
      mAbs, respectively. Our data clearly indicate that shear stress affects the
      migration behavior of PMN arrested on endothelium and suggest that binding to
      subendothelial extracellular matrix via beta1 integrins is another essential step
      in leukocyte extravasation.

PMID- 10915561
TI  - Splenocytes cultured in low concentrations of IL-2 generate NK cell specificities
      toward syngenic and allogenic targets.
AB  - Splenocytes cultured in the presence of 30-60 units/ml IL-2 for 5 days develop
      natural killer activity toward syngeneic and allogeneic tumor cell targets. The
      IL-2 activated splenocytes, themselves, are partially resistant, whereas
      concanavalin A-activated T blast cells are completely resistant to killing.
      Surprisingly, major histocompatibility complex (MHC)-I-negative target cells are
      also resistant to natural killer (NK)-cell-mediated killing. Cells resistant to
      killing were unable to block NK-cell-mediated killing of sensitive targets as
      judged from cold target cell inhibition experiments, and one type of target cells
      sensitive to killing did generally not cross-block killing of other killing
      sensitive target cell types. Alloantigen exposure of splenocytes, i.e., one-way
      mixed lymphocyte cultures, partially prevents the development of NK-cell
      activity. Our data suggest that target structures which trigger killing activity
      of NK cells are determined by the phenotype of the target cell and are dependent
      on its MHC class I expression disregarding the haplotype of the cell.

PMID- 10915562
TI  - The immune response modifiers imiquimod and R-848 are potent activators of B
      lymphocytes.
AB  - Imiquimod and R-848 are members of a family of immune response modifiers that
      stimulate cytokine production in monocyte/macrophages and dendritic cell
      cultures. This study evaluated the effects of the imidazoquinolines, imiquimod
      and R-848, on B lymphocyte activation. Both agents induced proliferation of
      murine T-cell-depleted and highly purified splenic B cell preparations as well as
      purified human B cells. Resting and activated B cells responded to these agents,
      with activated cells responding more efficiently. B cells from the LPS
      hyporesponsive C3H/HeJ mice and guanosine-hyporesponsive SJL mice proliferated in
      response to imiquimod and R-848, indicating a different mechanism of action than
      lipopolysaccharide and guanine nucleosides. B cells were also stimulated by
      imiquimod and R-848 to produce increased immunoglobulin levels. Increased
      expression of a number of B cell activation markers were seen following imiquimod
      or R-848 stimulation. Finally, R-848 was shown to act as a vaccine adjuvant
      enhancing OVA-specific IgG2a levels while suppressing total IgE. These results
      indicate that R-848 and imiquimod are potent activators of B lymphocytes and are
      capable of augmenting antigen-specific immunoglobulin production.

PMID- 10915563
TI  - Characterization of an IL-1 receptor from Asterias forbesi coelomocytes.
AB  - The tremendous importance of cytokines to immune defensive systems suggests that
      they have been conserved through evolution. The existence of interleukin (IL)-1
      like molecules in several invertebrate groups substantiates this hypothesis. To
      characterize further the relationship of invertebrate IL-1-like molecules, we
      have used competitive binding assays to show that invertebrate coelomocytes of
      the starfish Asterias forbesi possess an IL-1-specific binding protein.
      Competitive binding experiments used radiolabeled human IL-1alpha. IL-1 bound
      specifically to the coelomocytes by a single high-affinity binding site (K(d) =
      8.72 x 10(-10)/M). There are approximately 6000 binding sites per cell. The
      specificity of the receptor was confirmed by demonstrating that, among a group of
      cytokines and lymphokines tested, only vertebrate IL-1- or echinoderm IL-1-like
      molecules and the vertebrate IL-1 receptor antagonist inhibit IL-1 binding.
      Treatment of coelomocytes (labeled with IL-1alpha) with bivalent water-soluble
      crosslinkers identified a membrane protein of approximately 70 kDa to which IL-1
      is specifically crosslinked.

PMID- 10915564
TI  - Adult bone marrow stromal cells differentiate into neural cells in vitro.
AB  - Bone marrow stromal cells (BMSC) normally give rise to bone, cartilage, and
      mesenchymal cells. Recently, bone marrow cells have been shown to have the
      capacity to differentiate into myocytes, hepatocytes, and glial cells. We now
      demonstrate that human and mouse BMSC can be induced to differentiate into neural
      cells under experimental cell culture conditions. BMSC cultured in the presence
      of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural
      precursors. These cultures also expressed glial fibrillary acidic protein (GFAP)
      and neuron-specific nuclear protein (NeuN). When labeled human or mouse BMSC were
      cultured with rat fetal mesencephalic or striatal cells, a small proportion of
      BMSC-derived cells differentiated into neuron-like cells expressing NeuN and
      glial cells expressing GFAP.

PMID- 10915565
TI  - Chronic brain oxidation in a glutathione peroxidase knockout mouse model results
      in increased resistance to induced epileptic seizures.
AB  - Systemic administration of kainic acid (KA) to rodents results in limbic seizures
      and subsequent neurodegeneration similar to that observed in certain types of
      human epilepsy, and it is a commonly used animal model for this disease.
      Oxidative stress has been suggested to play a role in the neuronal injury
      associated with KA administration. Based on this observation, chronic treatment
      with antioxidants has been proposed as a possible protective therapy against
      neuronal damage associated with epileptic seizures. Here we demonstrate by
      histochemical, electrophysiological, and biochemical means that knockout mice
      with decreased activity of the protective antioxidant enzyme glutathione
      peroxidase, which display elevated basal brain oxidative stress levels, are
      resistant to KA-induced seizure activity and neurodegeneration. This appears to
      be a result of decreased NMDA receptor function due to oxidation of its NR1
      subunit. This suggests that the chronic use of antioxidants as antiepileptic
      agents to modulate NMDA-dependent seizure-induced neurodegeneration may be
      detrimental rather than protective and calls into question their use as a
      therapeutic agent in the treatment of epilepsy.

PMID- 10915566
TI  - Posthypoxic reoxygenation-induced neurotoxicity prevented by free radical
      scavenger and NMDA/non-NMDA antagonist in tandem as revealed by dynamic changes
      in glucose metabolism with positron autoradiography.
AB  - Using a positron autoradiography technique, dynamic changes in the cerebral
      glucose metabolic rate (CMRglc) induced by hypoxia/reoxygenation were
      investigated in living brain slices. After incubating fresh rat brain slices (300
      microm thick) with [(18)F]2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) in oxygenated
      Krebs-Ringer solution at 36 degrees C, serial two-dimensional time-resolved
      images of [(18)F]FDG uptake in the slices were obtained on imaging plates. As
      compared to the unloaded control values, with hypoxia-loading [(18)F]FDG uptake
      increased markedly, suggesting enhanced glycolysis. The net influx constant (K)
      of [(18)F]FDG at pre-hypoxia-loading and after reoxygenation with loading hypoxia
      for various periods of time was quantitatively evaluated by applying the Patlak
      graphical method to the image data. Regardless of the brain region, with hypoxia
      of </=10-min duration, the K value returned to the preloading level, whereas with
      hypoxia of >/=20 min duration only partial or no recovery was seen, indicating
      irreversible neuronal damage. The 30-min administration of either N-methyl-D
      aspartate (NMDA)/non-NMDA antagonist or a free radical scavenger at the same time
      as reoxygenation after 20 min hypoxia showed a neuroprotective effect inhibiting
      the decrease in the post-hypoxia-loading K value. In contrast, no such
      neuroprotective effect was evident with administration of either of these agents
      only during hypoxia loading, possibly indicating that immediately after
      reoxygenation neuronal damage was induced mediated by excitatory amino acids and
      free radicals in tandem. These results demonstrate that serial quantitative
      evaluation of CMRglc using this technique may be of use in investigating the
      brain tissue injury associated with hypoxia/reoxygenation as well as clarifying
      the underlying mechanisms and protective effect of various drugs against such
      injury.

PMID- 10915567
TI  - Basic fibroblast growth factor (bFGF) enhances functional recovery following
      severe spinal cord injury to the rat.
AB  - We have recently demonstrated that following a moderate contusion spinal cord
      injury (SCI) to rats, subsequent administration of basic fibroblast growth factor
      (bFGF) significantly enhances functional recovery and tissue sparing. To further
      characterize the effects of bFGF, we evaluated its efficacy after a more severe
      contusion injury at T(10) using the NYU impactor. Immediately after SCI, osmotic
      minipumps were implanted into the lateral ventricle and lumbar thecal sac to
      deliver bFGF at 3 or 6 microg per day versus control vehicle for 1 week. Animals
      were behaviorally tested for 6 weeks before histological assessment of tissue
      sparing through the injured segment and glial reactivity distal to the lesion.
      Compared to moderate SCI, all rats had more prolonged and sustained functional
      deficits 6 weeks after severe contusion. Subjects treated with bFGF had
      pronounced recovery of hindlimb movements from 2 to 6 weeks compared to controls,
      manifested in significantly higher behavioral scores. Only marginal tissue
      sparing was seen rostral to the injury in bFGF-treated spinal cords versus
      controls. Optical density measurements of astrocyte and microglial cell
      immunoreactivity in bFGF-treated spinal cords showed that after 6 weeks they
      approximated controls, although astrocyte immunoreactivity remained higher in
      controls rostrally. In summary, intrathecal infusion of bFGF following severe SCI
      significantly restores gross hindlimb motor function that is not correlated with
      significant tissue sparing. In light of previous evidence that pharmacological
      intervention with bFGF after moderate SCI enhances tissue preservation, the
      current findings indicate that yet undefined mechanisms contribute to the
      enhanced functional recovery following bFGF treatment.

PMID- 10915568
TI  - Schwann cells transplanted into normal and X-irradiated adult white matter do not
      migrate extensively and show poor long-term survival.
AB  - Although Schwann cells are able to enter the central nervous system (CNS) when
      the integrity of the glia limitans is disrupted, their ability to migrate through
      intact CNS remains unclear. We have addressed this issue by transplanting lacZ
      labeled Schwann cells into normal adult spinal cord white matter, and into X
      irradiated spinal cord (an environment that, unlike normal spinal cord, permits
      the migration of transplanted oligodendrocyte progenitors). Schwann cell
      cultures, obtained from neonatal rat sciatic nerve and expanded using bovine
      pituitary extract and forskolin, were transfected by repeated exposure to
      retroviral vectors encoding the Escherichia coli lacZ gene. The normal behavior
      of the transduced cells was confirmed by transplantation into a nonrepairing area
      of demyelination in the spinal cord, where they formed myelin sheaths around
      demyelinated axons. A single microliter containing 4 x 10(4) cells was then
      transplanted into unlesioned normal and X-irradiated white matter of the spinal
      cord of adult syngeneic rats. One hour after injection, blue cells were observed
      as a discrete mass within the dorsal funiculus with a longitudinal distribution
      of 2-3 mm, indicating the extent of passive spread of the injected cells. At
      subsequent survival times (1, 2, and 4 weeks posttransplantation) blue cells had
      a distribution that was no more extensive than that seen 1 h after
      transplantation. However, the number of Schwann cells declined with time
      following transplantation such that at 4 weeks there were few surviving Schwann
      cells in both X-irradiated and nonirradiated spinal cord. These results indicate
      that transplanted Schwann cells do not migrate extensively and show poor long
      term survival when introduced into a normal CNS environment.

PMID- 10915569
TI  - Mutual induction of TGFbeta1 and NGF after treatment with NGF or TGFbeta1 in
      grafted chromaffin cells of the adrenal medulla.
AB  - Chromaffin cells have been recognized for their ability to transform into
      sympathetic ganglion-like cells in response to nerve growth factor (NGF) or to
      stimulation of other neurotrophic factors. Transforming growth factor beta
      (TGFbeta) family members have been shown to potentiate the effect of different
      trophic factors. The aim of this study was to investigate if TGFbeta may
      influence NGF-induced neuronal transformation and regulation of NGF, TGFbeta1,
      and their receptors in the adult rat chromaffin tissue after grafting.
      Intraocular transplantation of adult chromaffin tissue was employed and grafts
      were treated with TGFbeta1 and/or NGF. Graft survival time was 18 days after
      which the grafts were processed for TGFbeta luciferase detection assay, NGF
      enzyme immunoassay, or in situ hybridization. In grafts stimulated with NGF,
      increased levels of TGFbeta1 and TGFbeta1 mRNA were detected. When grafts instead
      were treated with TGFbeta1, enhanced levels of NGF protein were found.
      Furthermore, a positive mRNA signal corresponding to the transforming growth
      factor II receptor (TbetaRII) was found in the chromaffin cells of the normal
      adrenal medulla as well as after grafting. No increase of TbetaRII mRNA levels
      was detected after transplantation or after TGFbeta1 treatment. Instead a
      reduction of TbetaRII mRNA expression was noted after NGF treatment. NGF
      stimulation of grafts increased the message for NGF receptors p75 and trkA in the
      chromaffin transplants. Grafts processed for evaluations of neurite outgrowth
      were allowed to survive for 28 days and were injected weekly with NGF and/or
      TGFbeta1. NGF treatment resulted in a robust innervation of the host irides.
      TGFbeta1 had no additive effect on nerve fiber formation when combined with NGF.
      Combined treatment of NGF and anti-TGFbeta1 resulted in a significantly larger
      area of reinnervation. In conclusion, it was found that NGF and TGFbeta1 may
      regulate the expression of each other's protein in adult chromaffin grafts.
      Furthermore, TbetaRII mRNA was present in the adult rat chromaffin cells and
      became downregulated as a result of NGF stimulation. Although no synergistic
      effects of TGFbeta1 were found on NGF-induced neurite outgrowth, it was found
      that TGFbeta1 and NGF signaling are closely linked in the chromaffin cells of the
      adrenal medulla.

PMID- 10915570
TI  - Exofocal alterations in opioidergic receptor densities following focal cerebral
      ischemia in the mouse.
AB  - In previous studies of our group, we have reported differential alterations in
      opioidergic receptor subtypes densities in infarcted and periinfarcted brain
      tissue following middle cerebral artery occlusion (MCAO) in mice. Other studies
      have also described subcortical alterations consecutive to focal cortical
      ischemia. For a better understanding of ischemic processes in exofocal areas, we
      have investigated the evolution of opioidergic receptors following focal cortical
      ischemia through the quantification of relative binding densities, B(max) and
      K(d) values for the mu, delta, and kappa subtypes. Our results demonstrate that
      opioid receptor subtypes exhibit adaptations at distance from the ischemic core,
      mainly in the striatum, the thalamus, and the substantia nigra. Indeed, mu and
      delta B(max) values were increased in ventral thalamic nuclei, while kappa
      relative binding densities were transiently increased in nucleus medialis
      dorsalis and nucleus lateralis, pars posterior. Moreover, the B(max) of mu and
      delta receptors were transiently decreased at 6 h post-MCAO in ipsi- and
      contralateral patches and matrices of the striatum. Conversely, the mu B(max)
      values were increased in ipsi- and contralateral substantia nigra, pars compacta,
      and pars reticulata, 24 h following MCAO. In contralateral substantia nigra, pars
      compacta, kappa B(max) was found to be decreased at 24 h post-MCAO. These
      alterations could reflect neuronal dysfunction in exofocal brain structures,
      consecutively to the degeneration of defined neuroanatomical pathways. Our study
      indicates that opioidergic receptors could be used as markers of the neuronal
      reorganization that take place in subcortical areas following an ischemic insult
      of the brain cortex.

PMID- 10915571
TI  - The expression of the calcium binding protein calretinin in the rat striatum:
      effects of dopamine depletion and L-DOPA treatment.
AB  - The activity of the striatum is regulated by glutamate and dopamine
      neurotransmission. Consequent to striatal dopamine depletion the corticostriatal
      excitatory input is increased, which in turn can raise intracellular calcium
      levels. We investigated changes in the neuronal expression of the calcium binding
      protein calretinin related to dopamine depletion and l-DOPA administration.
      Immunohistochemical methods were used to assess calretinin in the striatum of
      rats with unilateral lesions of the nigrostriatal system. In these animals we
      observed a loss of the patchy distribution of calretinin fibers. Moreover, after
      dopaminergic depletion we detected two new, not previously described, calretinin
      cell types, the presence of which could be related to morphological changes
      induced by loss of a dopaminergic input. We also found an increase in the number
      of calretinin-labeled cells in the striatum ipsilateral to the lesion compared to
      the contralateral striatum or to the striatum of normal rats. This increase was
      mostly evident at 3 weeks postlesion and tended to decrease toward normal levels
      at 6, 10, and 18 weeks postlesion. In unlesioned animals, l-DOPA administration
      did not induce changes in the expression of calretinin. In unilaterally lesioned
      animals, l-DOPA reversed the increase in the number of calretinin-positive cells
      induced by the lesion. However, chronic l-DOPA administration was less effective
      than acute l-DOPA in reversing the effect of the lesion. The present data
      suggests that striatal calretinin neurons are sensitive to dopamine depletion.
      Increased expression of calretinin in striatal cells may be consequent to
      enhanced striatal excitatory input.

PMID- 10915573
TI  - Effects of endogenous neurotrophins on sympathetic sprouting in the dorsal root
      ganglia and allodynia following spinal nerve injury.
AB  - Peripheral nerve injury is often complicated by a chronic pain syndrome that is
      difficult to treat. In animal models of peripheral nerve injury, sympathetic
      nerve terminals in the dorsal root ganglia (DRG) sprout to form baskets around
      large diameter neurons, an anatomical change that has been implicated in the
      induction of neuropathic pain. In the present study, we have investigated whether
      neurotrophins derived from peripheral sources play any roles in sympathetic
      sprouting and neuropathic pain in a rat model of peripheral nerve injury. After
      transection of the left lumbar (L) 5 spinal nerve, antisera specific to
      neurotrophins were injected intraperitoneally twice a week for 2 weeks. The foot
      withdrawal response to von Frey hairs was examined on days 1, 3, 7, 10, and 14
      postlesion. After completion of behavioral tests, sympathetic sprouting in DRG
      was examined by tyrosine hydroxylase (TH) immunohistochemistry. The number of TH
      immunoreactive (ir) fibers and baskets around large neurons within the lesioned
      DRG was dramatically increased in the rats treated with control normal sheep
      serum. Antisera specific to nerve growth factor (NGF), neurotrophin-3 (NT3), and
      brain-derived neurotrophic factor (BDNF) significantly reduced the sympathetic
      sprouting and the formation of baskets. L5 spinal nerve lesion induced a
      significant increase in foot withdrawal responses to von Frey hair stimuli, which
      was attenuated by treatment of antisera to neurotrophins with a different time
      sequential. The effect of BDNF antiserum occurred earlier and lasted longer than
      those of NGF and NT3 antisera. These results implicate that peripherally derived
      neurotrophins are involved in the induction of sympathetic sprouting and
      neuropathic pain following peripheral nerve injury.

PMID- 10915572
TI  - Long-lasting regulation of galanin, opioid, and other peptides in dorsal root
      ganglia and spinal cord during experimental polyarthritis.
AB  - Mechanisms involved in transition from acute to chronic pain are still not well
      understood and our means to therapeutically influence this transition are
      limited. Moreover, very little is known about long-lasting consequences of
      prolonged exposure to painful stimuli with regard to phenotypic changes and pain
      experience. In this study we have analyzed long term behavioral and neurochemical
      effects of intradermal tail injection of heat-killed mycobacterium butyricum
      suspended in complete Freund's adjuvant. Calcitonin gene-related peptide (CGRP)
      and galanin mRNA levels were investigated in dorsal root ganglia of polyarthritic
      rats during the acute (21-) and the remission stage (79 days postinjection), and
      opioid peptide mRNAs and receptors were studied in the spinal cord. Most of the
      increases in peptide mRNA levels observed during the acute stage of arthritis
      were still present in the remission stages. Thus, CGRP and galanin mRNAs in DRGs,
      and opioid peptide mRNAs and opioid receptors in the spinal cord were still
      strongly up-regulated, when animals do not exhibit spontaneous pain behavior and
      inflammation. Hot-plate test in the presence of naloxone, performed in the
      remission stage, indicated that opiates participate in pain threshold regulation
      after prolonged painful condition. Finally, X-ray examination revealed a complete
      destruction of joint structure, thus suggesting a parallel lesion of peripheral
      nerve endings. These results suggest that in the remission stage of chronic joint
      inflammation several types of mechanisms are activated aiming at counteracting
      both inflammatory and neuropathic pain. Thus, opioid systems in the dorsal horn
      as well as galanin in DRG neurons are upregulated, both alternating pain.

PMID- 10915574
TI  - Serotonin release from mesencephalic raphe neurons grafted to the 5,7
      dihydroxytryptamine-lesioned rat hippocampus: effects of behavioral activation
      and stress.
AB  - Transplants of fetal midbrain raphe neurons into the adult brain have been shown
      to promote recovery of complex behavioral deficits in several experimental
      models, but the mechanisms underlying these effects are only partially
      understood. In the present study, we have used a well-characterized model system
      to ascertain whether midbrain raphe graft can display behaviorally relevant
      changes in transmitter release and/or metabolism. Fetal mesencephalic raphe
      neurons were grafted unilaterally into the hippocampus previously deprived of its
      innate serotonergic innervation by intraventricular injections of 5,7
      dihydroxytryptamine. The contralateral hippocampus remained as a nongrafted,
      lesioned control. Microdialysis probes were implanted in the hippocampus 5-7
      months postgrafting. Under baseline conditions, extracellular levels of serotonin
      were similar to normal in the grafted hippocampi, but undetectable on the
      contralateral, nongrafted side. Levels of the serotonin metabolite, 5
      hydroxyindoleacetic acid (5-HIAA), were markedly higher than normal in the
      grafted hippocampi, but dramatically reduced on the contralateral nongrafted
      side. Handling stimulation (gentle stroking of a rat's fur and tail for 15 min)
      induced a 64% increase in serotonin output in the intact rats and a small but
      significant 12% increase in the grafted animals. Non-noxious tail-pinch (15 min)
      enhanced serotonin release by 86% in the intact rats and 28% in the grafted ones.
      Extracellular 5-HIAA levels remained unchanged during both handling and tail
      pinch in both the intact and the grafted rats. Forced immobilization of the rats
      for 15 min induced a transient 124% increase in extracellular serotonin levels in
      the intact rats and a significant 19% increase in the grafted animals, whereas
      swimming in temperate water (25-30 degrees C; 15 min) induced no detectable
      changes in serotonin output in any of the groups. 5-HIAA levels remained
      unchanged during forced immobilization, but were significantly reduced during the
      swimming session in both the intact (-38%) and grafted (-15%) animals. The
      present results indicate that median raphe grafts can become functionally
      integrated in the denervated host hippocampus and respond by altered indole
      output when the animal is exposed to different types of environmental challenges.

PMID- 10915575
TI  - Visualization of antigen-specific T cell activation in vivo in response to
      intracerebral administration of a xenopeptide.
AB  - Allogeneic or xenogenic tissues exhibit prolonged survival when grafted into the
      brain parenchyma in comparison to grafting into peripheral sites. The brain,
      therefore, has long been considered an immunologically privileged site. However,
      the immunological privilege of the brain is not absolute, and it cannot shield
      neural xenografts from rejection. In our laboratory, we are interested in
      determining how to prevent neural xenograft rejection. To do so, we need to first
      understand how the immune system responds to CNS antigens leading to graft
      rejection. In order to monitor immune system responses to CNS antigens an
      adoptive transfer system was used to directly track CNS antigen-specific CD4(+) T
      cell responses in vivo. This would then allow us to monitor changes in the
      number, activation state, and anatomic distribution of antigen-specific cells. We
      have found that, after intracerebral injection of xeno peptide antigens with
      adjuvant, antigen-specific cells accumulated in the cervical lymph node,
      proliferated there for several days, and then disappeared slowly from the nodes.
      Interestingly, peptide antigens given intracerebrally also stimulated a strong
      antigen-specific CD4(+) T cell response. Moreover, cells remaining in the lymph
      node 8 days after antigen stimulation produce IL-2 with secondary antigenic
      challenge. Previous studies have shown that the administration of antigens
      without adjuvant in a monomeric form via either the intraperitoneal or
      intravenous route has failed to induce cell-mediated immunity and resulted in
      antigen-specific T cell unresponsiveness. Our findings demonstrate that antigen
      delivered intracerebrally can activate immune responses in a manner different
      than antigen delivered to peripheral sites outside of the CNS.

PMID- 10915576
TI  - Distribution of calbindin, parvalbumin, and calretinin immunoreactivity in the
      reticular thalamic nucleus of the marmoset: evidence for a medial leaflet of
      incertal neurons.
AB  - The placement of the reticular thalamic nucleus (RTN) between the dorsal thalamus
      and the cortex and the inhibitory nature of reticulothalamic projections has led
      to suggestions that it "gates" the flow of sensory information to the cortex. The
      New World diurnal monkey, the marmoset, Callithrix jacchus is emerging as an
      important "model primate" for the study of sensory processing. We have examined
      the distribution of Nissl-stained somata and calbindin, parvalbumin, and
      calretinin immunoreactivity in the ventral thalamus for comparison with other
      species. Cells were labeled using standard immunohistochemistry, ExtraAvidin-HRP,
      and diaminobenzidine reaction products. The RTN is constituted by a largely
      homogeneous population of parvalbumin immunoreactive cells with respect to size
      and orientation. Calbindin and calretinin immunoreactive cells were only found
      along the medial edge of the RTN adjacent to the external medullary lamina of the
      dorsal thalamus and laterally near the ventral RTN. These cells were considered
      to be part of the zona incerta (ZI). The marmoset ZI could be subdivided into
      dorsal and ventral regions on the basis of its immunoreactivity to calcium
      binding proteins. Both the ZI and nucleus subthalamicus Luysi contained scattered
      calbindin and calretinin immunoreactive cells with well-defined dendritic
      processes. These cells were clearly different to cells in the dorsal thalamus.
      Parvalbumin immunoreactive cells in RTN, ZI, and subthalamic nucleus were on
      average larger than neurons positive for the other calcium binding proteins.
      Future studies reporting the afferent and efferent projections to the RTN must
      view their results in terms of the close apposition of RTN and ZI somata.

PMID- 10915577
TI  - Expression of sodium channel SNS/PN3 and ankyrin(G) mRNAs in the trigeminal
      ganglion after inferior alveolar nerve injury in the rat.
AB  - The inferior alveolar nerve is a sensory branch of the trigeminal nerve that is
      frequently damaged, and such nerve injuries can give rise to persistent
      paraesthesia and dysaesthesia. The mechanisms behind neuropathic pain following
      nerve injury is poorly understood. However, remodeling of voltage-gated sodium
      channels in the neuronal membrane has been proposed as one possible mechanism
      behind injury-induced ectopic hyperexcitability. The TTX-resistant sodium channel
      SNS/PN3 has been implicated in the development of neuropathic pain after spinal
      nerve injury. We here study the effect of chronic axotomy of the inferior
      alveolar nerve on the expression of SNS/PN3 mRNA in trigeminal sensory neurons.
      The organization of sodium channels in the neuronal membrane is maintained by
      binding to ankyrin, which help link the sodium channel to the membrane skeleton.
      Ankyrin(G), which colocalizes with sodium channels in the initial segments and
      nodes of Ranvier, and is necessary for normal neuronal sodium channel function,
      could be essential in the reorganization of the axonal membrane after nerve
      injury. For this reason, we here study the expression of ankyrin(G) in the
      trigeminal ganglion and the localization of ankyrin(G) protein in the inferior
      alveolar nerve after injury. We show that SNS/PN3 mRNA is down-regulated in small
      sized trigeminal ganglion neurons following inferior alveolar nerve injury but
      that, in contrast to the persistent loss of SNS/PN3 mRNA seen in dorsal root
      ganglion neurons following sciatic nerve injury, the levels of SNS/PN3 mRNA
      appear to normalize within a few weeks. We further show that the expression of
      ankyrin(G) mRNA also is downregulated after nerve lesion and that these changes
      persist for at least 13 weeks. This decrease in the ankyrin(G) mRNA expression
      could play a role in the reorganization of sodium channels within the damaged
      nerve. The changes in the levels of SNS/PN3 mRNA in the trigeminal ganglion,
      which follow the time course for hyperexcitability of trigeminal ganglion neurons
      after inferior alveolar nerve injury, may contribute to the inappropriate firing
      associated with sensory dysfunction in the orofacial region.

PMID- 10915578
TI  - Characterization of audiogenic-like seizures in naive rats evoked by activation
      of AMPA and NMDA receptors in the inferior colliculus.
AB  - The role of glutamate receptors in the inferior colliculus (IC) in audiogenic and
      audiogenic-like seizures was investigated in adult rats with transient neonatal
      hypothyroidism by 0.02% propylthiouracil (PTU) treatment through mother's milk
      (PTU rats) and in naive rats treated intracisternally with N-methyl-d-aspartate
      (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), or
      cyclothiazide, an inhibitor of rapid AMPA receptor desensitization. All rats
      showed audiogenic or audiogenic-like seizures characterized by running fit (RF)
      and generalized tonic-clonic seizures (GTCS). While systemically administered MK
      801 inhibited GTCS, intracisternally administered NBQX inhibited RF and GTCS in
      both audiogenic and audiogenic-like seizures. Auditory stimulation shortened the
      latency to GTCS induced by AMPA, but not NMDA, at a subclinical dose and further
      elongated the shortened duration of RF, but not GTCS, induced by MK-801
      pretreatment. Furthermore, Northern blot analysis was used to evaluate the
      expression of the immediate-early gene c-fos in the IC following induction of
      audiogenic or audiogenic-like seizures. The significant induction of c-fos mRNA
      by audiogenic seizures in PTU rats or by AMPA- or cyclothiazide-induced seizures
      in naive rats was prominent in the IC. MK-801 suppressed c-fos mRNA expression in
      the IC induced by audiogenic seizures in PTU rats or by AMPA-induced seizures in
      naive rats. NBQX suppressed the expression of c-fos mRNA in the IC induced by
      AMPA-induced seizures but did not suppress c-fos mRNA in PTU rats or rats with
      cyclothiazide-induced seizures. Auditory stimuli failed to affect c-fos mRNA
      induction by AMPA. The present study suggests that audiogenic-like seizures can
      be reproduced by glutamate receptor agonists in which AMPA receptors are
      primarily linked to the initiation of audiogenic seizures (RF) while NMDA
      receptors presumably located within the IC are involved in the propagation of
      GTCS in audiogenic seizures.

PMID- 10915579
TI  - Compensatory projection of primary nociceptors and c-fos induction in the spinal
      dorsal horn following neonatal sciatic nerve lesion.
AB  - The sciatic nerve was cut in newborn rats, and prevented from regenerating for 8
      weeks. The number of dorsal root ganglion (DRG) neurons in L4 and L5, the
      distribution of central axon terminals of primary nociceptors, and the activity
      of secondary nociceptors were examined in the lumbar dorsal horn. The neonatal
      sciatic lesion caused about 60% reduction of DRG neurons. The central terminal
      field of the sciatic primary nociceptors negatively labeled by in situ binding of
      Bandeiraea simplicifolia isolectin B4 (BsIB4) markedly shriveled. Instead, the
      central representation of the saphenous nerve and the posterior cutaneous nerve
      of the thigh (PC) expanded. The laminae I/II neuropil in the medialmost (1/4) of
      the L3 dorsal horn and in the second lateral (1/4) around the L4/5 junction was
      occupied by the BsIB4 binding sites derived from the saphenous and the PC primary
      neurons, respectively. Noxious stimuli applied to the receptive fields of the
      saphenous and the PC nerves induced c-Fos-like immunoreactivity in many neurons
      in the expanded central terminal fields of the nerves. The collateral sprouts of
      uninjured primary nociceptors did not only invade the deafferented area of the
      dorsal horn but also established functional synaptic connections.

PMID- 10915580
TI  - Quantitative biochemical and ultrastructural comparison of mitochondrial
      permeability transition in isolated brain and liver mitochondria: evidence for
      reduced sensitivity of brain mitochondria.
AB  - Opening of the mitochondrial permeability transition pore has increasingly been
      implicated in excitotoxic, ischemic, and apoptotic cell death, as well as in
      several neurodegenerative disease processes. However, much of the work directly
      characterizing properties of the transition pore has been performed in isolated
      liver mitochondria. Because of suggestions of tissue-specific differences in pore
      properties, we directly compared isolated brain mitochondria with liver
      mitochondria and used three quantitative biochemical and ultrastructural
      measurements of permeability transition. We provide evidence that brain
      mitochondria do not readily undergo permeability transition upon exposure to
      conditions that rapidly induce the opening of the transition pore in liver
      mitochondria. Exposure of liver mitochondria to transition-inducing agents led to
      a large, cyclosporin A-inhibitable decrease in spectrophotometric absorbance, a
      loss of mitochondrial glutathione, and morphologic evidence of matrix swelling
      and disruption, as expected. However, we found that similarly treated brain
      mitochondria showed very little absorbance change and no loss of glutathione. The
      absence of response in brain was not simply due to structural limitations, since
      large-amplitude swelling and release of glutathione occurred when membrane pores
      unrelated to the transition pore were formed. Additionally, electron microscopy
      revealed that the majority of brain mitochondria appeared morphologically
      unchanged following treatment to induce permeability transition. These findings
      show that isolated brain mitochondria are more resistant to induction of
      permeability transition than mitochondria from liver, which may have important
      implications for the study of the mechanisms involved in neuronal cell death.

PMID- 10915582
TI  - International Society of Regulatory Toxicology and Pharmacology 1999
      International Achievement Award.

PMID- 10915581
TI  - Transplants of adrenal medullary chromaffin cells reduce forelimb and hindlimb
      allodynia in a rodent model of chronic central pain after spinal cord hemisection
      injury.
AB  - In the majority of patients, spinal cord injury (SCI) results in abnormal pain
      syndromes in which non-noxious stimuli become noxious (allodynia). To reduce
      allodynia, it would be desirable to implant a permanent biological pump such as
      adrenal medullary chromaffin cells (AM), which secrete catecholamines and opioid
      peptides, both antinociceptive substances, near the spinal cord. We tested this
      approach using a recently developed a mammalian SCI model of chronic central
      pain, which results in development of mechanical and thermal allodynia. Thirty
      day-old male Sprague-Dawley rats were spinally hemisected at T13 and allowed 4
      weeks for recovery of locomotor function and development of allodynia.
      Nonimmunosuppressed injured animals received either control-striated muscle (n =
      7) or AM (n = 10) transplants. Nociceptive behavior was tested for 4 weeks
      posttransplant as measured by paw withdrawals to von Frey filaments, radiant
      heat, and pin prick stimuli. Hemisected animals receiving AM demonstrated
      statistically significant reductions in both fore- and hindlimb mechanical and
      thermal allodynia, but not analgesia, when compared to hemisected animals
      receiving striated muscle transplants (P < 0.05). Tyrosine hydroxylase
      immunoreactivity indicated prolonged transplant survival and production of
      catecholamines. HPLC analysis of cerebrospinal fluid samples from animals
      receiving AM transplants demonstrated statistically significant increases in
      levels of dopamine (sevenfold), norepinephrine (twofold), and epinephrine
      (threefold), compared to control values several weeks following transplant (P <
      0.05). By 28 days posttransplant, however, antinociceptive effects were
      diminished. These results support the therapeutic potential of transplanted AM in
      reducing chronic central pain following spinal cord injury.

PMID- 10915583
TI  - International society of regulatory toxicology and pharmacology 1999
      international achievement award

PMID- 10915584
TI  - The FQPA: a challenge for science policy and pesticide regulation.

PMID- 10915585
TI  - Pesticides and infant risk: is there a need for an additional safety margin?

PMID- 10915586
TI  - Differences in sensitivity of children and adults to chemical toxicity: the NAS
      panel report.
AB  - The National Academy of Sciences (NAS) Committee on Pesticides in the Diets of
      Infants and Children worked for some 4 years to evaluate the extent and the
      health-related consequences of exposure of infants and children to pesticides.
      The focus of this paper is on deliberations and recommendations of the committee
      relevant to protection of infants and children from toxic effects of pesticides.
      The most comprehensive data available for contrasting the toxicity of chemicals
      in the young and adults were compilations of rodent mortality studies. Age
      dependent differences in chemical lethality were less than 1 order of magnitude
      and usually varied no more than 2- to 3-fold. Findings in studies of pesticides
      and other chemicals revealed that toxicity was age- and compound-dependent. The
      younger and more immature the subject, the more different its response from that
      of an adult. Substantial anatomical, biochemical, and physiological changes occur
      during infancy, childhood, and adolescence. These maturational changes can
      substantially affect the absorption, distribution, metabolism, and elimination of
      chemicals. The net effect of immaturity on pharmacokinetics and pharmacodynamics
      is difficult to predict. Measurements of physiological functions in different age
      groups can be made and input into physiologically based pharmacokinetic (PBPK)
      models. The committee felt that PBPK models could be effectively utilized for
      different exposure scenarios, to predict the time course of potentially toxic
      chemicals and metabolites in different organs of children. The committee
      recognized that maturing organ systems of infants and children may be susceptible
      to injury by chemicals. There may be developmental periods (i.e., windows of
      vulnerability) when the endocrine, reproductive, immune, visual, or nervous
      systems are particularly sensitive to certain chemicals. The committee
      recommended early assessments using sensitive indices of injury to these organ
      systems of test animals. Only limited information was available on the
      therapeutic efficacy and toxicity of drugs in pediatric populations. The most
      definitive data were maximally tolerated doses (MTDs) of chemotherapeutic agents.
      MTDs were frequently higher for children than adults, though the differences
      between age groups were usually < or =2. It was concluded by the NAS committee
      that immaturity does not necessarily entail greater sensitivity to chemical
      toxicity; age-dependent toxicity is chemical-dependent; and the existing 10-fold
      interspecies uncertainty factor provides adequate protection of infants and
      children, based on current knowledge.

PMID- 10915587
TI  - An analysis of the need for an additional uncertainty factor for infants and
      children.
AB  - Uncertainty factors have been used for over 40 years to establish safe intakes of
      threshold toxicants. Tenfold factors are used to allow for species differences
      and for human variability, with extra factors for database inadequacies. The
      proposal to introduce an additional 10-fold factor for pesticides when exposure
      of infants and children is anticipated implies either age-related differences
      between species or differences within humans which exceed those present in
      adults. Alternatively, the extra factor could be related to deficiencies of
      current testing methods or concerns over irreversibility in developing organ
      systems. Available data do not provide a scientific rationale for the extra
      factor due to inadequacy of inter- and intraspecies uncertainty factors.
      Justification for the factor therefore must relate to the adequacy and
      sensitivity of current methods or concern about irreversible effects in the
      developing organism.

PMID- 10915588
TI  - Pesticide residues in food: problems and data needs.

PMID- 10915589
TI  - Risk metrics and cumulative risk assessment methodology for the FQPA.
AB  - The Food Quality Protection Act (FQPA) of 1996 mandates that the U.S.
      Environmental Protection Agency consider both aggregate and cumulative risks.
      Aggregate assessments account for multiple sources and routes of exposure for a
      single chemical. Cumulative assessments combine exposures to two or more
      chemicals that share a common mechanism of toxicity. Probabilistic risk
      assessment methods are described for determining a population's distribution of
      the dose from exposure and the combination of that exposure characterization with
      appropriate toxicological information to form a risk assessment. An individual's
      dose from exposure is characterized as a set of chemical- and route-specific dose
      profiles over time. For each individual and each chemical and route, a margin of
      exposure (MOE) is calculated by dividing a toxicologically relevant benchmark
      dose (e.g., an ED(10)) by the individual's dose from exposure. The set of these
      MOEs for an individual is combined into the individual's Total MOE. The
      distribution of the Total MOEs in a population is compared to an Acceptable MOE.
      Advantages of the Total MOE approach over approaches based on reference doses are
      discussed. Some general comments on risk metrics are made, and some general
      guidance for cumulative risk assessments is provided.

PMID- 10915590
TI  - FQPA science issues: common mechanism of toxicity and cumulative risk assessment.

PMID- 10915591
TI  - Summary of product characteristic: the next step to harmonization registration
      requirements for veterinary medicinal products in Poland.

PMID- 10915592
TI  - Cytokine-mediated control of viral infections.

PMID- 10915593
TI  - Chemokines and viruses: the dearest enemies.
AB  - The relation between viruses and the chemokine system is characterized by a
      complex blend of enmity and attraction. Chemokines are key regulators of innate
      and adaptive immune responses against invading microorganisms, including viruses.
      They act not only as immune system "traffic officers," controlling leukocyte
      migration under both physiological and pathological conditions, but also as fine
      orchestrators that modulate the induction, amplification, and cytokine-secretion
      pattern of antiviral responses. However, viruses have succeeded in turning the
      chemokine system into an ally. During the course of a long parallel evolution,
      viruses have captured from their hosts the genetic information for encoding
      chemokines and chemokine receptors and have reprogrammed it for evading the
      control of the immune system. Moreover, selected viral agents, most notably
      primate immunodeficiency retroviruses, have adopted chemokine receptors as
      essential gateways for entry into their target cells. The endogenous secretion of
      chemokines is thus emerging as an important in vivo mechanism of viral control,
      which is potentially inducible by effective vaccines. The deepening knowledge of
      the interactions between viruses and chemokines may lead to novel therapeutic and
      preventive strategies for the control of viral and inflammatory diseases.

PMID- 10915594
TI  - Mapping of domains on the human parainfluenza type 2 virus P and NP proteins that
      are involved in the interaction with the L protein.
AB  - Eleven monoclonal antibodies (MAbs) directed against the large (L) protein of
      human parainfluenza type 2 virus (hPIV-2) were prepared to examine the
      interactions of the L protein with other viral proteins. Coimmunoprecipitation
      assays using these MAbs revealed that the L protein directly interacted with the
      phospho- (P) and nucleocapsid (NP) proteins in vivo and in vitro. Mutational
      analysis of the P or NP protein was performed to identify the region(s) on these
      proteins interacting with L protein, indicating that amino acids 278-353 on the P
      protein and amino acids 403-494 on the NP protein are essential for the binding
      to the L protein.

PMID- 10915595
TI  - Expression of the human poliovirus receptor/CD155 gene during development of the
      central nervous system: implications for the pathogenesis of poliomyelitis.
AB  - The gene for the human poliovirus receptor (hPVR/CD155) is the founding member of
      a new family of genes encoding proteins belonging to the immunoglobulin
      superfamily. To determine whether CD155 is expressed during mammalian
      development, we have made use of the previously characterized promoter of the
      CD155 gene and generated mice transgenic for a CD155 promoter-driven beta
      galactosidase reporter gene. Expression of the reporter gene in transgenic
      embryos was observed during midgestation in anterior midline structures of the
      developing central nervous system and in the neuroretina. During that period,
      reporter gene expression appeared within the notochord and floor plate along the
      entire spinal cord reaching into the caudal diencephalon. In addition, transgene
      expression was observed in axonal projections emanating from retinal ganglion
      cells forming the optic nerve to reach the future region of the optic chiasm.
      Analysis of expression of CD155 during human embryonic development confirmed the
      distribution of reporter gene expression specified by CD155 promoter activity.
      The anatomical distribution of CD155 promoter activity during embryogenesis
      matches that of transacting factors previously identified to regulate
      transcription of the CD155 gene. Expression of CD155 within embryonic structures
      giving rise to spinal cord anterior horn motor neurons may explain the
      restrictive host cell tropism of poliovirus for this cellular compartment of the
      CNS.

PMID- 10915597
TI  - Tobacco mosaic virus replicase-mediated cross-protection: contributions of RNA
      and protein-derived mechanisms.
AB  - Specific sequences of the tobacco mosaic virus (TMV) RNA-dependent RNA-polymerase
      (RdRp) gene were investigated for their ability to confer cross-protection. Nine
      overlapping segments ranging from 713 to 1070 nucleotides in length and covering
      the methyltransferase, helicase, and polymerase (POL) domains of the TMV RdRp
      open reading frame were systemically expressed in Nicotiana benthamiana using a
      potato X virus (PVX) vector [Chapman, S., Kavanagh, T., and Baulcombe, D. C.
      (1992). Plant J., 1, 549-557]. PVX-infected plants were subsequently challenge
      inoculated with 10 microg of wild-type TMV and monitored for TMV accumulation.
      Mock inoculated plants and plants preinfected with the unmodified PVX vector
      rapidly accumulated high levels of challenge virus. In contrast, plants
      preinfected with PVX vectors expressing segments of the TMV RdRp open reading
      frame displayed either high or low levels of protection. High protection levels
      were observed for PVX constructs expressing segments of the TMV POL domain,
      whereas low protection levels were observed for PVX constructs expressing
      segments covering the methyltransferase and helicase domains. Frameshift
      mutations that blocked protein expression from RdRp segments disrupted only the
      high levels of protection derived from POL segments and not the low levels
      derived from the other segments. However, all RdRp segments conferred similarly
      high levels of protection against a TMV construct with restricted local movement.
      Thus both RNA and protein sequences in conjunction with the speed of the
      infecting challenge virus can affect the protection derived from the TMV RdRp
      gene.

PMID- 10915596
TI  - Cell-to-cell and systemic movement of recombinant green fluorescent protein
      tagged turnip crinkle viruses.
AB  - To facilitate analyses of turnip crinkle virus (TCV) cell-to-cell and systemic
      movement, we created a series of recombinant viruses expressing green fluorescent
      protein (GFP) either as substitutions of coat protein (CP) sequences or as
      fusions to movement proteins (MPs). Constructs were used to inoculate leaves of
      Arabidopsis seedlings. TCV carrying its two native MPs and GFP fused near the
      start of CP translation (GFP DeltaCP) resulted in cell-to-cell movement
      manifested by the expansion of fluorescent foci on inoculated leaves. GFP fusions
      to either MP were inactive for movement. However, TCV carrying the p9-GFP fusion,
      which expresses a functional p8 gene, could be complemented for cell-to-cell
      movement by coinoculation with virus carrying native p9 but mutant for p8. This
      same coinoculation combination also lead to systemic spread of GFP fluorescence
      to noninoculated leaves, as the complementing virus carries native CP.
      Complementation for systemic movement of virus carrying GFP DeltaCP constructs
      was achieved by inoculation onto transgenic plants expressing TCV CP. GFP-tagged
      TCV movement was detected throughout the plant, including the inflorescence stem,
      cauline leaves, flowers, siliques, and substructures such as organ primordia and
      meristematic regions. The recombinant viruses described herein provide (1)
      genetic information relevant to define regions of TCV that can, or cannot, be
      manipulated by insertion of foreign coding sequences and (2) a set of tools to
      allow the study of viral cell-to-cell and long-distance movement in the model
      plant system Arabidopsis.

PMID- 10915598
TI  - Nuclear localization of turnip crinkle virus movement protein p8.
AB  - Turnip crinkle virus (TCV) is a single-stranded positive-sense RNA virus of the
      Carmovirus genus. Two of its five open reading frames (ORFs), encoding proteins
      of 8 and 9 kDa, are required for cell-to-cell movement of the virus. These
      movement proteins (MPs) were fused to green fluorescent protein (GFP) to
      determine their cellular localization. In protoplasts, p9-GFP, like GFP itself,
      is found throughout the cytoplasm, as well as in cell nuclei. In contrast, p8-GFP
      was confined to the cell nucleus. Similar localization patterns were observed
      when specific small peptide epitopes were fused to p8 and p9 proteins instead of
      GFP. The cytoplasmic localization of p9-GFP and nuclear localization of p8-GFP
      were also detected in leaves after particle bombardment of DNA encoding these
      fusion proteins or after overexpression of p8-GFP in transgenic Arabidopsis
      seedlings. The expression of the GFP fusion proteins by recombinant TCV viruses
      in infected protoplasts or on inoculated Arabidopsis leaves produced similar
      patterns. Unlike TMV-MP and other MPs studied to date, no obvious punctuate
      expression in the cell wall or association with the cytoskeleton was detected.
      The sequence analysis of p8 revealed two unique nuclear localization signals
      (NLSs), which were not conserved within p8 homologues of other viruses in the
      genus Carmovirus. Mutation in either of these NLSs did not disrupt the nuclear
      localization of p8-GFP. However, when both NLSs were mutated, p8-GFP expression
      was no longer restricted to cell nuclei. The NLSs are not required for cell-to
      cell movement; TCV recombinant viruses mutated in one or both NLSs could still
      facilitate cell-to-cell movement of the virus. The nuclear localization of p8
      suggests a novel function for this protein in the cell nucleus.

PMID- 10915599
TI  - Enhanced replication contributes to enrichment of hepatitis B virus with a
      deletion in the core gene.
AB  - Accumulation in immunosuppressed patients of hepatitis B virus (HBV) with a
      deletion in the C gene is associated with severe liver disease. The aim of this
      study was to determine the phenotype of such genomes in vitro. Four C gene
      fragments with different types of deletions were inserted in the context of a
      wild-type genome and tested by transfection into HuH7 cells. The deletions did
      not influence mRNA and surface protein levels. Truncated C gene translation
      products were expressed only from variants with in-frame deletions, whereas full
      length polymerase was expressed from all variants at a similar or higher level
      than in wild-type virus. None of the variants was competent for autonomous
      replication; however, they produced 2- to 4.5-fold more progeny DNA than wild
      type HBV when sufficiently complemented with wild-type core protein. Similarly,
      when variant and wild-type DNA were cotransfected in different ratios, the
      variants produced 2- to 5-fold more progeny DNA relative to the wild-type; this
      enrichment required the expression of the viral polymerase in cis. The mechanism
      of enrichment depended on the percentage of variant in the transfected DNA
      mixture. When the transfected DNA contained a small percentage of variant,
      enhanced replication of the variant accompanied by no or little suppression of
      wild-type replication was seen. Accordingly, overall production of progeny virus
      was slightly increased. At a high percentage of variant DNA, replication of both
      variant and wild-type decreased, probably due to a shortage of wild-type core
      protein. In conclusion, emergence of C gene deletion variants in vivo may be due
      to enhanced replication mediated at the level of encapsidation or reverse
      transcription. If the variants constitute a small part of the ccc DNA, they can
      be fully trans-complemented by wild-type virus which may increase the overall
      virus production.

PMID- 10915600
TI  - Strain-specific interaction of the tobacco etch virus NIa protein with the
      translation initiation factor eIF4E in the yeast two-hybrid system.
AB  - The NIa protein of potyviruses provides VPg and proteolytic functions during
      virus replication. It has also been shown to confer host genotype-specific
      movement functions in plants. Specifically, NIa from tobacco etch virus (TEV)
      Oxnard, but not from most other strains, confers the ability to move long
      distances in Nicotiana tabacum cultivar "V-20." This led to the hypothesis that
      all or part of NIa may interact with one or more cellular factors. To identify
      cellular proteins that interact with NIa in a host- or strain-specific manner, a
      yeast two-hybrid search of a tomato cDNA library was done. Ten proteins that
      interacted with NIa were recovered, with translation initiation factor eIF4E
      being by far the most common protein identified. Interaction of eIF4E with NIa
      was shown to be TEV strain-specific. eIF4E from both tomato and tobacco
      interacted well with NIa from the HAT strain, but not from the Oxnard strain.
      However, using chimeric NIa proteins, the determinant for systemic infection of
      V20 plants was found to be genetically distinct from the determinant controlling
      eIF4E interaction. In TEV-eIF4E coexpression experiments, evidence suggesting
      that eIF4E provides a positive effect on genome amplification was obtained.

PMID- 10915601
TI  - LuSIV cells: a reporter cell line for the detection and quantitation of a single
      cycle of HIV and SIV replication.
AB  - A single cycle of viral replication is the time required for a virus to enter the
      host cell, replicate its genome, and produce infectious progeny virions. The
      primate lentiviruses, human immunodeficiency virus (HIV) and simian
      immunodeficiency virus (SIV), require on average 24 h to complete one cycle of
      replication. We have now developed and characterized a reporter assay system in
      CEMx174 cells for the quantitative measurement of HIV/SIV infection within a
      single replication cycle. The SIV(mac)239 LTR (-225 --> +149) was cloned upstream
      of the firefly luciferase reporter gene and this reporter plasmid is maintained
      in CEMx174 cells under stable selection. This cell line, designated LuSIV, is
      highly sensitive to infection by primary and laboratory strains of HIV/SIV,
      resulting in Tat-mediated expression of luciferase, which correlates with viral
      infectivity. Furthermore, manipulation of LuSIV cells for the detection of
      luciferase activity is easy to perform and requires a minimal amount of time as
      compared to current HIV/SIV detection systems. The LuSIV system is a powerful
      tool for the analysis of HIV/SIV infection that provides a unique assay system
      that can detect virus replication prior to 24 h and does not require virus to
      spread from cell to cell. Thus these cells can be used for the study of
      replication-deficient viruses and the high throughput screening of antivirals, or
      other inhibitors of infection.

PMID- 10915602
TI  - Role of the DExH motif of the Japanese encephalitis virus and hepatitis C virus
      NS3 proteins in the ATPase and RNA helicase activities.
AB  - The role of the conserved DExH motif of the Japanese encephalitis virus (JEV) NS3
      protein in the ATPase and RNA helicase activities was compared with that of the
      hepatitis C virus (HCV) NS3 protein. In the DExH motif of JEV NS3, Asp-285 and
      Glu-286 were essential for both ATPase and RNA helicase activities. Cys-287 was
      critical for the RNA helicase activity of JEV NS3 but not for ATPase activity. A
      His-288-to-Ala substitution in the DExH motif of HCV NS3 resulted in an increase
      in ATPase activity which was suppressed by poly(U). In contrast, alanine
      substitution at the same site in JEV NS3 did not increase basal ATPase activity
      which remained to be stimulated by poly(U). Thus, the mutational effect at His in
      motif II was different in the HCV and JEV NS3 proteins. Mutagenesis at His-288 of
      JEV NS3 revealed that His was the most preferable amino acid for ATPase activity
      and Ala, Gly, Asn, Gln, Ser, or Arg could partly substitute for it. However, any
      other mutation at His-288 completely disrupted the RNA helicase activity of JEV
      NS3. The results suggest that Cys-287 and His-288 are essential residues
      especially for the RNA helicase activity of JEV NS3 and the ATPase and helicase
      activities are separable enzymatic functions.

PMID- 10915603
TI  - Cloning of an infectious milk-borne mouse mammary tumor virus (MMTV) DNA from a
      mammary tumor that developed in an endogenous MMTV-free wild mouse.
AB  - Molecular characterization of infectious mouse mammary tumor viruses (MMTVs) has
      been hampered due to the problem of cloning a full-length exogenous virus into a
      plasmid. The present report describes our strategy for obtaining a full-length
      clone of an exogenous MMTV from a mouse mammary tumor that arose spontaneously in
      a wild Chinese mouse free of endogenous MMTV and shows that the cloned virus (JYG
      MMTV) is expressed in rat RBA cells. Four-week-old C58/J x CBA/CaJ female mice,
      free of both endogenous and exogenous MMTVs, were injected with virus-secreting
      RBA cells. The progeny of these mice were bred, and their offspring were tested
      for the presence of MMTV. These third-generation mice were found to actively
      produce MMTV that was shed in their milk and transmitted to their offspring. The
      virus was detected not only in the mammary glands of these young mice, but also
      in their spleens and bone marrow. These results suggest that our plasmid-cloned
      exogenous JYG-MMTV is infectious. This virus can now be used effectively in
      manipulating the various genes of JYG-MMTV and other MMTV strains to understand
      their structure/function relationships.

PMID- 10915604
TI  - Human monoclonal antibody 98-6 reacts with the fusogenic form of gp41.
AB  - A mixture of two peptides from gp41 (N36 and C34) forms an alpha-helical
      structure that is thought to represent the fusogenic form of gp41. A human anti
      gp41 monoclonal antibody (mAb 98-6), generated from the cells of an infected
      individual, reacted poorly with C34, but binding was strongly enhanced when N36
      was added, indicating that the mAb reacts with a conformational epitope present
      in the fusogenic structure formed by the interaction of peptides N36 and C34. The
      epitope recognized by mAb 98-6 was found in lysates of virions on oligomeric
      forms of gp41 (dimers, trimers, and tetramers). On infected cells, the epitope
      was present as oligomers of gp41, as monomers of gp41, and as part of the
      envelope polyprotein gp160, obtained after biotinylation of intact cells, which
      were then lysed and immunoprecipitated with various mAbs. In lysates of infected
      cells, the epitope was present as part of both monomeric gp41 and gp160. These
      studies demonstrate that infected humans can respond to the fusogenic form of
      gp41 and that the anti-gp41 mAb studied here recognizes a conformational epitope
      formed by the interaction of two regions of gp41, which forms an alpha-helical
      bundle. This epitope is found on several forms of gp41 as it occurs in virions,
      on the surface of infected cells, and in infected cells.

PMID- 10915605
TI  - Sequence parameters that determine specificity of binding of the replication
      associated protein to its cognate site in two strains of tomato leaf curl virus
      New Delhi.
AB  - The DNA binding sites for the replication-associated protein (Rep) of two strains
      of tomato leaf curl virus from New Delhi (ToLCV-Nde) were identified using
      electrophoretic mobility shift assays (EMSAs). The Rep proteins of the two
      strains were found to exhibit sequence specificity in recognition of their
      cognate repeat motifs (iterons) in the origin, despite the fact that they share
      91% sequence identity. Using a series of synthetic oligonucleotides as probes in
      EMSAs, the interaction of Rep protein with its binding site was found to be
      dependent on number, size, and sequence of the two iterons. Mutations in the
      sequence of the repeat motifs or alteration in the arrangement of the motifs
      compromised the ability of Rep protein to bind the DNA sequence and reduced
      accumulation of viral DNA in protoplasts, suggesting that binding of Rep protein
      to its cognate iterons is an essential step in virus replication. In addition, a
      difference in sequence of two base pairs in the binding site of two ToLCV-Nde
      strains was found to affect DNA binding by the corresponding Rep protein and
      replication of the virus DNA in protoplasts.

PMID- 10915606
TI  - NS3 serine protease of bovine viral diarrhea virus: characterization of active
      site residues, NS4A cofactor domain, and protease-cofactor interactions.
AB  - The gene expression of bovine viral diarrhea virus (BVDV), a pestivirus, occurs
      via translation of a hypothetical polyprotein that is processed cotranslationally
      and posttranslationally by viral and cellular enzymes. A protease located in the
      N-terminal region of nonstructural (NS) protein NS3 catalyzes the cleavages,
      leading to the release of NS4A, NS4B, NS5A, and NS5B. Our study provides
      experimental evidence that histidine at position 1658 and aspartic acid at
      position 1686 constitute together with the previously identified serine at
      position 1752 (S1752) the catalytic triad of the pestiviral NS3 serine protease.
      Interestingly, a mutant protease encompassing an exchange of the active site
      S1752 to threonine still showed residual activity. This finding links the NS3
      protease of pestiviruses to the capsid protease of Sindbis virus. Furthermore, we
      observed that the minimal protease domain of NS3 encompasses about 209 amino
      acids. The NS3 protease was found to be sensitive to N-terminal truncation
      because a deletion of 6 amino acids significantly reduced the cleavage efficiency
      at the NS4A/4B site. Larger N-terminal deletions also impaired the activity of
      the enzyme with respect to the other cleavage sites but to a different degree at
      each site. The NS3 protease of BVDV has previously been shown to depend on NS4A
      as cofactor. We demonstrate here that the central region of NS4A represents the
      cofactor domain. Furthermore, coprecipitation studies strongly suggest an
      interaction between NS4A and the N-terminal region of NS3. Besides the remarkable
      similarities observed between the pestiviral NS3 protease and the corresponding
      enzyme of hepatitis C virus (HCV), our results suggest a common ancestry between
      these enzymes and the capsid protease of Sindbis virus.

PMID- 10915607
TI  - Selection of a subgroup A avian leukosis virus [ALV(A)] envelope resistant to
      soluble ALV(A) surface glycoprotein.
AB  - The host developing resistance to retroviral infection is believed to be a major
      force in the evolution of multiple receptor usage by retroviruses. The avian
      leukosis-sarcoma virus (ALV) group of retroviruses provides a powerful system for
      studying the envelope-receptor interactions involved in retrovirus entry;
      different members of this group of closely related viruses use distinct cellular
      receptors. Analysis of the ALV envelope subgroups suggests that the different
      ALVs evolved from a common ancestor by mutations in the env gene. Cells and
      animals that express subgroup A ALV envelope glycoproteins are highly resistant
      to ALV(A) infection due to receptor interference. In this study, we tested
      whether expression of a soluble form of subgroup A surface glycoprotein (SU)
      would result in receptor interference and whether this interference would select
      for resistant viruses with altered receptor usage. Chicken cells expressing the
      secreted ALV(A) SU immunoadhesin SU(A)-rIgG, which contains the subgroup A SU
      domain fused to the constant region of a rabbit immunoglobulin (IgG) heavy chain,
      showed significant receptor interference. A variant virus resistant to SU(A)-rIgG
      receptor interference was obtained. This virus had a six-amino-acid deletion in
      the subgroup A hr1 that altered receptor usage. This approach may identify
      regions of SU that play a critical role in receptor specificity.

PMID- 10915608
TI  - Papillomavirus virus-like particles for the delivery of multiple cytotoxic T cell
      epitopes.
AB  - Chimeric papillomavirus (PV) virus-like particles (VLPs) based on the bovine
      papillomavirus type 1 (BPV-1) L1 protein were constructed by replacing the 23
      carboxyl-terminal amino acids of the BPV1 major protein L1 with an artificial
      "polytope" minigene, containing known CTL epitopes of human PV16 E7 protein, HIV
      IIIB gp120 P18, Nef, and reverse transcriptase (RT) proteins, and an HPV16 E7
      linear B epitope. The CTL epitopes were restricted by three different MHC class I
      alleles (H-2(b), H-2(d), HLA-A*0201). The chimeric L1 protein assembled into VLPs
      when expressed in SF-9 cells by recombinant baculovirus. After immunization of
      mice with polytope VLPs in the absence of adjuvant, serum antibodies were
      detected which reacted with both polytope VLPs and wild-type BPV1L1 VLPs, in
      addition to the HPV16E7 linear B cell epitope. CTL precursors specific for the
      HPV16 E7, HIV P18, and RT CTL epitopes were also detected in the spleen of
      immunized mice. Polytope VLPs can thus deliver multiple B and T epitopes as
      immunogens to the MHC class I and class II pathways, extending the utility of
      VLPs as self-adjuvanting immunogen delivery systems.

PMID- 10915609
TI  - The brown algal virus EsV-1 particle contains a putative hybrid histidine kinase.
AB  - The Ectocarpus siliculosus virus, EsV-1, occurs worldwide in all populations of
      the filamentous marine brown alga E. siliculosus. We have screened an expression
      library of EsV-1 restriction fragments and identified a DNA clone with the
      potential to code for a 52-kDa histidine protein kinase. The derived amino acid
      sequence includes all homology boxes diagnostic for histidine protein kinases
      and, in addition, amino acid motifs that are commonly found in response
      regulators of bacterial two-component signal transduction proteins. Thus, the
      novel viral protein can be classified as a hybrid histidine protein kinase of a
      type that has previously been detected in fungi, slime molds, and plants. By
      using purified antibodies, we found that the protein with its potential kinase
      activity is located on the outer shell of viral particles. This is the first
      report on a two-component regulator-like protein in viruses and could provide the
      basis for speculations with regard to the evolution of EsV-1 and related viruses.

PMID- 10915610
TI  - The RNA encompassing the internal ribosome entry site in the poliovirus 5'
      nontranslated region enhances the encapsidation of genomic RNA.
AB  - Poliovirus replicons were constructed which contain the internal ribosome entry
      site (IRES) of encephalomyocarditis virus (EMCV) substituted for the poliovirus
      IRES. To monitor gene expression and encapsidation, the gene encoding firefly
      luciferase was substituted for the P1 gene. Replicons can be encapsidated
      following serial passage in the presence of a recombinant vaccinia virus, VV-P1,
      which expresses the poliovirus P1 protein following infection. Encapsidation of
      the wild-type replicon (PV-Luc) was accomplished at either 33 or 37 degrees C;
      the lower temperature actually resulted in greater amounts of encapsidated
      replicon. In contrast, the replicon with the EMCV IRES element (EMCV-Luc) was not
      efficiently encapsidated at 37 degrees C and, following serial passage with VV-P1
      at 37 degrees C, was not amplified. EMCV-Luc was efficiently encapsidated,
      however, following serial passage with VV-P1 at 33 degrees C. Using the
      encapsidated EMCV-Luc obtained at 33 degrees C, we found that cells infected with
      EMCV-Luc at 33 or 37 degrees C produced similar amounts of luciferase.
      Encapsidated EMCV-Luc and PV-Luc had similar thermal stability at 33 and 37
      degrees C. A single-round encapsidation analysis revealed that less EMCV-Luc was
      encapsidated at 37 than at 33 degrees C; less EMCV-Luc was encapsidated at 33
      degrees C compared to PV-Luc at either 37 or 33 degrees C. The results of our
      studies suggest that in addition to influencing translation/replication, the IRES
      region of poliovirus can function to enhance encapsidation.

PMID- 10915611
TI  - Rare etiology of autosomal recessive disease in a child with noncarrier parents.
AB  - A child with maple syrup urine disease type 2 (MSUD2) was found to be homozygous
      for a 10-bp MSUD2-gene deletion on chromosome 1. Both purported parents were
      tested, and neither carries the gene deletion. Polymorphic simple-sequence repeat
      analyses at 15 loci on chromosome 1 and at 16 loci on other chromosomes confirmed
      parentage and revealed that a de novo mutation prior to maternal meiosis I,
      followed by nondisjunction in maternal meiosis II, resulted in an oocyte with two
      copies of the de novo mutant allele. Fertilization by a sperm that did not carry
      a paternal chromosome 1 or subsequent mitotic loss of the paternal chromosome 1
      resulted in the propositus inheriting two mutant MSUD2 alleles on two maternal
      number 1 chromosomes.

PMID- 10915612
TI  - Somatic and germline mosaic mutations in the doublecortin gene are associated
      with variable phenotypes.
AB  - Mutations in the X-linked gene doublecortin lead to "double cortex" syndrome (DC)
      in females and to X-linked lissencephaly (XLIS) in males. Because most patients
      with DC and XLIS are sporadic, representing de novo doublecortin mutations, we
      considered that some of these patients could be somatic or germline mosaics.
      Among a population of 20 patients and their families, we found evidence for
      mosaic doublecortin mutations in 6 individuals. Germline mosaicism was identified
      in two unaffected women, each with two affected children. Additionally, one
      affected male with DC was found to be a somatic mosaic, which presumably spared
      him from the more severe phenotype of lissencephaly. The high rate of mosaicism
      indicates that there may be a significant recurrence risk for DC/XLIS in families
      at risk, even when the mother is unaffected.

PMID- 10915613
TI  - A novel locus for autosomal recessive peripheral neuropathy in the EGR2 region on
      10q23.
AB  - During our studies of Romany (Gypsy) families with hereditary motor and sensory
      neuropathy-Lom, we have identified a large kindred with two independently
      segregating autosomal recessive neuropathies. The novel disorder, named
      "hereditary motor and sensory neuropathy-Russe" (HMSNR), presented as a severe
      disabling form of Charcot-Marie-Tooth disease with prominent sensory loss,
      moderately reduced motor nerve conduction velocity, and a high threshold for
      electrical nerve stimulation. A genome scan in two branches of the large kindred
      detected linkage to the 10q22-q23 region containing the early growth response 2
      gene (EGR2), a transcription factor with a key role in peripheral nerve
      myelination. The results of sequence analysis and the detection of an intragenic
      polymorphism allowed us to exclude EGR2 as the HMSNR gene. Further analysis done
      using linkage and recombination mapping refined the position of the HMSNR gene to
      a small interval on 10q23.2, flanked by markers D10S581 and D10S1742, telomeric
      to EGR2. In this interval, a conserved seven-marker haplotype is shared by all
      disease chromosomes, suggesting a single founder mutation. The homozygosity
      region is contained in bacterial-artificial-chromosome contig 1570 of the Sanger
      Centre physical map and has an estimated physical size of approximately 500 kb.

PMID- 10915614
TI  - Primates--a natural heritage of conflict resolution.
AB  - The traditional notion of aggression as an antisocial instinct is being replaced
      by a framework that considers it a tool of competition and negotiation. When
      survival depends on mutual assistance, the expression of aggression is
      constrained by the need to maintain beneficial relationships. Moreover, evolution
      has produced ways of countering its disruptive consequences. For example,
      chimpanzees kiss and embrace after fights, and other nonhuman primates engage in
      similar "reconciliations." Theoretical developments in this field carry
      implications for human aggression research. From families to high schools,
      aggressive conflict is subject to the same constraints known of cooperative
      animal societies. It is only when social relationships are valued that one can
      expect the full complement of natural checks and balances.

PMID- 10915615
TI  - Dysfunction in the neural circuitry of emotion regulation--a possible prelude to
      violence.
AB  - Emotion is normally regulated in the human brain by a complex circuit consisting
      of the orbital frontal cortex, amygdala, anterior cingulate cortex, and several
      other interconnected regions. There are both genetic and environmental
      contributions to the structure and function of this circuitry. We posit that
      impulsive aggression and violence arise as a consequence of faulty emotion
      regulation. Indeed, the prefrontal cortex receives a major serotonergic
      projection, which is dysfunctional in individuals who show impulsive violence.
      Individuals vulnerable to faulty regulation of negative emotion are at risk for
      violence and aggression. Research on the neural circuitry of emotion regulation
      suggests new avenues of intervention for such at-risk populations.

PMID- 10915617
TI  - An organic solid state injection laser.
AB  - We report on electrically driven amplified spontaneous emission and lasing in
      tetracene single crystals using field-effect electrodes for efficient electron
      and hole injection. For laser action, feedback is provided by reflections at the
      cleaved edges of the crystal resulting in a Fabry-Perot resonator. Increasing the
      injected current density above a certain threshold value results in the
      decreasing of the spectral width of the emission from 120 millielectron volts to
      less than 1 millielectron volt because of gain narrowing and eventually laser
      action. High electron and hole mobilities as well as balanced charge carrier
      injection lead to improved exciton generation in these gate-controlled devices.
      Moreover, the effect of charge-induced absorption is substantially reduced in
      high-quality single crystals compared with amorphous organic materials.

PMID- 10915618
TI  - Low-friction nanoscale linear bearing realized from multiwall carbon nanotubes
AB  - We demonstrate the controlled and reversible telescopic extension of multiwall
      carbon nanotubes, thus realizing ultralow-friction nanoscale linear bearings and
      constant-force nanosprings. Measurements performed in situ on individual custom
      engineered nanotubes inside a high-resolution transmission electron microscope
      demonstrated the anticipated van der Waals energy-based retraction force and
      enabled us to place quantitative limits on the static and dynamic interwall
      frictional forces between nested nanotubes. Repeated extension and retraction of
      telescoping nanotube segments revealed no wear or fatigue on the atomic scale.
      Hence, these nanotubes may constitute near perfect, wear-free surfaces.

PMID- 10915616
TI  - Evidence for the prion hypothesis: induction of the yeast [PSI+] factor by in
      vitro- converted Sup35 protein.
AB  - Starting with purified, bacterially produced protein, we have created a [PSI(+)]
      inducing agent based on an altered (prion) conformation of the yeast Sup35
      protein. After converting Sup35p to its prion conformation in vitro, we
      introduced it into the cytoplasm of living yeast using a liposome transformation
      protocol. Introduction of substoichiometric quantities of converted Sup35p
      greatly increased the rate of appearance of the well-characterized epigenetic
      factor [PSI+], which results from self-propagating aggregates of cellular Sup35p.
      Thus, as predicted by the prion hypothesis, proteins can act as infectious agents
      by causing self-propagating conformational changes.

PMID- 10915619
TI  - Full three-dimensional photonic bandgap crystals at near-infrared wavelengths
AB  - An artificial crystal structure has been fabricated exhibiting a full three
      dimensional photonic bandgap effect at optical communication wavelengths. The
      photonic crystal was constructed by stacking 0.7-micrometer period semiconductor
      stripes with the accuracy of 30 nanometers by advanced wafer-fusion technique. A
      bandgap effect of more than 40 decibels (which corresponds to 99.99% reflection)
      was successfully achieved. The result encourages us to create an ultra-small
      optical integrated circuit including a three-dimensional photonic crystal
      waveguide with a sharp bend.

PMID- 10915620
TI  - Synthesis and characterization of helical multi-shell gold nanowires
AB  - Suspended gold nanowires were made in an ultra-high vacuum. The finest of them
      was 0.6 nanometer in diameter and 6 nanometers in length. By high-resolution
      electron microscopy, they were shown to have a multi-shell structure composed of
      coaxial tubes. Each tube consists of helical atom rows coiled round the wire
      axis. The difference between the numbers of atom rows in outer and inner shells
      is seven, resulting in magic shell-closing numbers.

PMID- 10915621
TI  - Rapid kimberlite ascent and the significance of Ar-Ar ages in xenolith
      phlogopites
AB  - Kimberlite eruptions bring exotic rock fragments and minerals, including
      diamonds, from deep within the mantle up to the surface. Such fragments are
      rapidly absorbed into the kimberlite magma so their appearance at the surface
      implies rapid transport from depth. High spatial resolution Ar-Ar age data on
      phlogopite grains in xenoliths from Malaita in the Solomon Islands, southwest
      Pacific, and Elovy Island in the Kola Peninsula, Russia, indicate transport times
      of hours to days depending upon the magma temperature. In addition, the data show
      that the phlogopite grains preserve Ar-Ar ages recorded at high temperature in
      the mantle, 700 degrees C above the conventional closure temperature.

PMID- 10915622
TI  - A potent greenhouse gas identified in the atmosphere: SF(5)CF(3)
AB  - We detected a compound previously unreported in the atmosphere, trifluoromethyl
      sulfur pentafluoride (SF(5)CF(3)). Measurements of its infrared absorption cross
      section show SF(5)CF(3) to have a radiative forcing of 0.57 watt per square meter
      per parts per billion. This is the largest radiative forcing, on a per molecule
      basis, of any gas found in the atmosphere to date. Antarctic firn measurements
      show it to have grown from near zero in the late 1960s to about 0.12 part per
      trillion in 1999. It is presently growing by about 0.008 part per trillion per
      year, or 6% per year. Stratospheric profiles of SF(5)CF(3) suggest that it is
      long-lived in the atmosphere (on the order of 1000 years).

PMID- 10915623
TI  - CLAVATA3, a multimeric ligand for the CLAVATA1 receptor-kinase.
AB  - The CLAVATA1 (CLV1) and CLAVATA3 (CLV3) proteins form a potential receptor and
      ligand pair that regulates the balance between cell proliferation and
      differentiation at the shoot meristem of Arabidopsis. CLV1 encodes a receptor
      kinase, and CLV3 encodes a predicted small, secreted polypeptide. We demonstrate
      that the CLV3 and CLV1 proteins coimmunoprecipitate in vivo, that yeast cells
      expressing CLV1 and CLV2 bind to CLV3 from plant extracts, and that binding
      requires CLV1 kinase activity. CLV3 only associates with the presumed active CLV1
      protein complex in vivo. More than 75% of CLV3 in cauliflower extracts is bound
      with CLV1, consistent with hypotheses of ligand sequestration. Soluble CLV3 was
      found in an approximately 25-kilodalton multimeric complex.

PMID- 10915624
TI  - Dependence of stem cell fate in Arabidopsis on a feedback loop regulated by CLV3
      activity.
AB  - The fate of stem cells in plant meristems is governed by directional signaling
      systems that are regulated by negative feedback. In Arabidopsis thaliana, the
      CLAVATA (CLV) genes encode the essential components of a negative, stem cell
      restricting pathway. We used transgenic plants overexpressing CLV3 to show that
      meristem cell accumulation and fate depends directly on the level of CLV3
      activity and that CLV3 signaling occurs exclusively through a CLV1/CLV2 receptor
      kinase complex. We also demonstrate that the CLV pathway acts by repressing the
      activity of the transcription factor WUSCHEL, an element of the positive, stem
      cell-promoting pathway.

PMID- 10915625
TI  - A structural model of transcription elongation.
AB  - The path of the nucleic acids through a transcription elongation complex was
      tracked by mapping cross-links between bacterial RNA polymerase (RNAP) and
      transcript RNA or template DNA onto the x-ray crystal structure. In the resulting
      model, the downstream duplex DNA is nestled in a trough formed by the beta'
      subunit and enclosed on top by the beta subunit. In the RNAP channel, the RNA/DNA
      hybrid extends from the enzyme active site, along a region of the beta subunit
      harboring rifampicin resistance mutations, to the beta' subunit "rudder." The
      single-stranded RNA is then extruded through another channel formed by the beta
      subunit flap domain. The model provides insight into the functional properties of
      the transcription complex.

PMID- 10915626
TI  - Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor.
AB  - Spermatozoa undergo a poorly understood activation process induced by bicarbonate
      and mediated by cyclic adenosine 3',5'-monophosphate (cAMP). It has been assumed
      that bicarbonate mediates its effects through changes in intracellular pH or
      membrane potential; however, we demonstrate here that bicarbonate directly
      stimulates mammalian soluble adenylyl cyclase (sAC) activity in vivo and in vitro
      in a pH-independent manner. sAC is most similar to adenylyl cyclases from
      cyanobacteria, and bicarbonate regulation of cyclase activity is conserved in
      these early forms of life. sAC is also expressed in other bicarbonate-responsive
      tissues, which suggests that bicarbonate regulation of cAMP signaling plays a
      fundamental role in many biological systems.

PMID- 10915627
TI  - Altered nociceptive neuronal circuits after neonatal peripheral inflammation.
AB  - Nociceptive neuronal circuits are formed during embryonic and postnatal times
      when painful stimuli are normally absent or limited. Today, medical procedures
      for neonates with health risks can involve tissue injury and pain for which the
      long-term effects are unknown. To investigate the impact of neonatal tissue
      injury and pain on development of nociceptive neuronal circuitry, we used an
      animal model of persistent hind paw peripheral inflammation. We found that, as
      adults, these animals exhibited spinal neuronal circuits with increased input and
      segmental changes in nociceptive primary afferent axons and altered responses to
      sensory stimulation.

PMID- 10915628
TI  - Central role for the lens in cave fish eye degeneration.
AB  - Astyanax mexicanus is a teleost with eyed surface-dwelling and eyeless cave
      dwelling forms. Eye formation is initiated in cave fish embryos, but the eye
      subsequently arrests and degenerates. The surface fish lens stimulates growth and
      development after transplantation into the cave fish optic cup, restoring optic
      tissues lost during cave fish evolution. Conversely, eye growth and development
      are retarded following transplantation of a surface fish lens into a cave fish
      optic cup or lens extirpation. These results show that evolutionary changes in an
      inductive signal from the lens are involved in cave fish eye degeneration.

PMID- 10915629
TI  - Synaptic integration mediated by striatal cholinergic interneurons in basal
      ganglia function.
AB  - The physiological role of striatal cholinergic interneurons was investigated with
      immunotoxin-mediated cell targeting (IMCT). Unilateral cholinergic cell ablation
      caused an acute abnormal turning behavior. These mice showed gradual recovery but
      displayed abnormal turning by both excess stimulation and inhibition of dopamine
      actions. In the acute phase, basal ganglia function was shifted to a hyperactive
      state by stimulation and suppression of striatonigral and striatopallidal
      neurons, respectively. D1 and D2 dopamine receptors were then down-regulated,
      relieving dopamine-predominant synaptic perturbation but leaving a defect in
      controlling dopamine responses. The acetylcholine-dopamine interaction is
      concertedly and adaptively regulated for basal ganglia synaptic integration.

PMID- 10915630
TI  - Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis.
AB  - Liver fibrosis is characterized by activation of hepatic stellate cells, which
      are then involved in synthesis of matrix proteins and in regulating matrix
      degradation. In the acute phases of liver injury and as liver fibrosis
      progresses, there is increased expression of matrix metalloproteinases (MMPs) and
      their tissue inhibitors (TIMPs). Among the changes described, striking features
      include increased expression of gelatinase A (MMP-2) and membrane type 1-MMP
      (MT(1)-MMP; MMP-14) as well as TIMP-1 and TIMP-2. These molecules and other
      family members are involved in regulating degradation of both normal and fibrotic
      liver matrix. This article outlines recent progress in this field and discusses
      the mechanisms by which MMPs and TIMPs may contribute to the progression and
      regression of liver fibrosis. Recently described properties of MMPs and TIMPs of
      relevance to the pathogenesis of liver fibrosis are outlined. The proposal that
      regression of liver fibrosis is mediated by decreased expression of TIMPs and
      involves degradation of fibrillar collagens by a combination of MT(1)-MMP and
      gelatinase A, in addition to interstitial collagenase, is explored.

PMID- 10915631
TI  - Molecular physiology and pathophysiology of tight junctions I. Tight junction
      structure and function: lessons from mutant animals and proteins.
AB  - Tight junctions form the major paracellular barrier in epithelial tissues.
      Barrier-sealing properties are quite variable among cell types in terms of
      electrical resistance, solute and water flux, and charge selectivity. A molecular
      explanation for this variability appears closer following identification of the
      transmembrane proteins occludin and members of the claudin multigene family. For
      example, the human phenotype of mutations in claudin-16 suggests that it creates
      a channel that allows magnesium to diffuse through renal tight junctions.
      Similarly, a mouse knockout of claudin-11 reveals its role in formation of tight
      junctions in myelin and between Sertoli cells in testis. The study of other
      claudins is expected to elucidate their contributions to creating junction
      structure and physiology in all epithelial tissues.

PMID- 10915632
TI  - Disruption of primary and secondary esophageal peristalsis by afferent
      stimulation.
AB  - Recent studies have shown that afferent signals originating from the pharynx
      inhibit progression of primary esophageal peristalsis. Our aim was to further
      elucidate the effect of esophageal and pharyngeal afferent stimulation on primary
      and secondary esophageal peristalsis. We studied the effect of esophageal air
      distension and pharyngeal water stimulation on progression of primary and
      secondary peristalsis in nine healthy volunteers aged 27 +/- 2 yr (4 men, 5
      women). At a threshold volume, rapid injection of water into the pharynx,
      directed posteriorly, resulted in complete halt of the progressing secondary and
      primary esophageal peristalses in both the proximal and distal esophagus. The
      threshold volume of injected water for inducing inhibition was similar for
      secondary (0.6 +/- 0.2 ml) and primary (0.5 +/- 0.1 ml) esophageal peristalsis.
      Progression of primary peristalsis induced by a dry swallow and secondary
      peristalsis induced by intraesophageal air distension were completely inhibited
      by intraesophageal injection of 15 +/- 2 ml of air in 70% and 75% of the trials,
      respectively. We conclude that afferent signals induced by esophageal air
      distension and pharyngeal water stimulation inhibit propagation of both primary
      and secondary esophageal peristalsis, suggesting a shared neural control
      mechanism for these types of peristalsis.

PMID- 10915633
TI  - Upper esophageal sphincter function during gastroesophageal reflux events
      revisited.
AB  - Upper esophageal sphincter (UES) function during gastroesophageal reflux events
      is not completely elucidated because previous studies addressing this issue
      yielded conflicting results. We reexamined the UES pressure response to
      intraluminal esophageal pressure and pH changes induced by reflux events. We
      studied 14 healthy, asymptomatic volunteers (age 49 +/- 6 yr) and 7
      gastroesophageal reflux disease patients (age 48 +/- 5 yr). UES pressure,
      intraesophageal pressure, and pH were monitored at the distal, middle, and
      proximal esophagus concurrently in the supine position 1 h before and 2 h after a
      1,000-calorie meal. A total of 321 reflux events were identified by the
      development of abrupt reflux-induced intraesophageal pressure increase (IPI); 285
      events occurred in patients and 36 in control subjects. In control subjects 33 of
      36 and in patients 252 of 285 IPI events were associated with a pH drop. Among
      patients and control subjects, 99% and 100%, respectively, of all IPI events
      irrespective of pH drop were associated with abrupt increase in UES pressure (34
      +/- 2 and 27 +/- 6 mmHg, respectively). The average percentage of maximum UES
      pressure increase over prereflux values ranged between 66% and 96% (control
      subjects) and 34% and 122% (patients). IPIs induced by both acidic and nonacidic
      reflux events evoke strong UES contractile responses.

PMID- 10915634
TI  - Expression and canalicular localization of two isoforms of the ClC-3 chloride
      channel from rat hepatocytes.
AB  - The molecular identities of functional chloride channels in hepatocytes are
      largely unknown. We examined the ClC-3 chloride channel in rat hepatocytes and
      found that mRNA for two different isoforms is present. A short form is identical
      to the previously reported sequence for rat ClC-3, and a long form contains a 176
      bp insertion immediately upstream of the translation initiation site. This
      predicts a 58-amino acid NH(2) terminal insertion. Both long and short form mRNA
      was expressed in diverse tissues of the rat. Transient transfection of the long
      form in CHO-K1 cells resulted in currents with an I(-) > B(-) > Cl(-) selectivity
      sequence, outward rectification, and inactivation at positive voltages. Short
      form currents had identical ionic selectivity but displayed a more extreme
      outward rectification and showed no voltage-dependent inactivation.
      Immunofluorescence and immunoblots localized native ClC-3 preferentially but not
      exclusively to the canalicular membrane. We have therefore identified a new
      isoform of rat ClC-3 and shown that expression of both isoforms produces
      functional channels. In hepatocytes, ClC-3 is located in association with the
      canalicular membrane.

PMID- 10915635
TI  - Basolateral outward rectifier chloride channel in isolated crypts of mouse colon.
AB  - Single channel patch-clamp techniques were used to demonstrate the presence of
      outwardly rectifying chloride channels in the basolateral membrane of crypt cells
      from mouse distal colon. These channels were rarely observed in the cell-attached
      mode and, in the inside-out configuration, only became active after a delay and
      depolarizing voltage steps. Single channel conductance was 23.4 pS between -100
      and -40 mV and increased to 90.2 pS between 40 and 100 mV. The channel
      permeability sequence for anions was: I(-) > SCN(-) > Br(-) > Cl(-) > NO(3)(-) >
      F(-)>> SO(4)(2-) approximately gluconate. In inside-out patches, the channel open
      probability was voltage dependent but insensitive to intracellular Ca(2+)
      concentration. In cell-attached mode, forskolin, histamine, carbachol, A-23187,
      and activators of protein kinase C all failed to activate the channel, and
      activity could not be evoked in inside-out patches by exposure to the purified
      catalytic subunit of cAMP-dependent protein kinase A. The channel was inhibited
      by 5-nitro-2-(3-phenylpropylamino)benzoate, 9-anthracenecarboxylic acid, and
      DIDS. Stimulation of G proteins with guanosine 5'-O-(3-thiotriphosphate)
      decreased the channel open probability and conductance, whereas subsequent
      addition of guanosine 5'-O-(2-thiodiphosphate) reactivated the channel.

PMID- 10915636
TI  - Enteral nutrient intake level determines intestinal protein synthesis and
      accretion rates in neonatal pigs.
AB  - Our objective was to determine the minimum enteral intake level necessary to
      increase the protein accretion rate (PAR) in the neonatal small intestine. Seven
      day-old piglets received an equal total daily intake of an elemental diet, with
      different proportions given enterally (0, 10%, 20%, 40%, 60%, 80%, and 100%).
      After 7 days, piglets were infused intravenously with [(2)H(3)]leucine for 6 h,
      and the fractional protein synthesis rate (FSR) was measured in the proximal (PJ)
      and distal jejunum (DJ) and the proximal (PI) and distal ileum (DI). The jejunal
      FSR increased from 45%/day to 130%/day between 0 and 60% enteral intake, whereas
      the FSR in the ileum was less sensitive to enteral intake level. At 0% enteral
      intake, PAR was significantly negative in the PJ, DJ, and PI (range -70 to -43
      mg/day) and positive in the DI (49 mg/day), whereas intestinal protein balance
      occurred at 20% enteral intake. At 100% enteral intake, the PAR was greatest in
      the DI, even though the rates of protein turnover were 50% lower than in the PJ.
      We conclude that there is net intestinal protein loss at 0% enteral intake,
      protein balance at 20% enteral intake, and maximal intestinal protein accretion
      at 60% enteral intake.

PMID- 10915637
TI  - Cellular mechanism of sodium oleate-stimulated secretion of cholecystokinin and
      secretin.
AB  - Long-chain fatty acids are potent stimulants of secretin and CCK release. The
      cellular mechanisms of fatty acid-stimulated secretion of these two hormones are
      not clear. We studied the stimulatory effect and mechanism of sodium oleate (SO)
      on secretin- and CCK-producing cells. SO stimulated the release of secretin or
      CCK from isolated rat mucosal cell preparations enriched in either secretin- or
      CCK-producing cells, respectively. SO also time- and dose-dependently stimulated
      secretin and CCK release from STC-1 cells. In STC-1 cells, SO-stimulated secretin
      and CCK release was potentiated by IBMX and inhibited by a protein kinase A
      selective inhibitor and a cAMP-specific antagonist. SO-stimulated releases of the
      two hormones were also inhibited by downregulation or inhibitors of protein
      kinase C, a calmodulin antagonist and an inhibitor of calmodulin-dependent
      protein kinase II. Chelating of extracellular Ca(2+) or addition of an L-type
      calcium channel blocker diminished SO-stimulated hormone releases. SO caused an
      increase in intracellular Ca(2+) concentration that was partially reversed by
      diltiazem but had no effect on production of cAMP, cGMP, or inositol-1,4,5
      triphosphate. These results indicate that SO acts on secretin- and CCK-producing
      cells. Its stimulatory effect is potentiated by endogenous protein kinase A and
      mediated by activation of Ca(2+) influx through the L-type channels and of
      protein kinase C and Ca(2+)/calmodulin-dependent protein kinase II.

PMID- 10915638
TI  - Biological activities of novel lipid mediator sphingosine 1-phosphate in rat
      hepatic stellate cells.
AB  - Sphingosine 1-phosphate (S-1-P), a lipid mediator shown to be a ligand for aortic
      G protein-coupled receptor [corrected] (AGRs), endothelial differentiation gene
      (EDG)1, EDG3, and AGR16/EDG5, is stored in platelets and released on their
      activation. Platelet consumption occurs in acute liver injury. Hepatic stellate
      cells (HSCs) play an important role in wound healing. Effects of S-1-P on HSCs
      were investigated. S-1-P enhanced proliferation of culture-activated HSCs. The
      mitogenic effect was pertussis toxin sensitive, mitogen-activated protein kinase
      dependent, and more prominent at lower cell density. S-1-P increased contraction
      of collagen lattices containing HSCs, irrespective of activation state, in a C3
      exotoxin-sensitive manner. mRNAs of EDG1 and AGR16, but not of EDG3, were
      detected in HSCs. In HSC activation, EDG1 mRNA levels were downregulated, whereas
      AGR16 mRNA levels were unchanged. Considering that HSCs are capable of production
      of extracellular matrices and modulation of blood flow in sinusoids, our results
      suggest that S-1-P may play a role in wound healing process in the liver.

PMID- 10915639
TI  - Mice lacking the dopamine transporter display altered regulation of distal
      colonic motility.
AB  - The mechanisms by which dopamine (DA) influences gastrointestinal (GI) tract
      motility are incompletely understood and complicated by tissue- and species
      specific differences in dopaminergic function. To improve the understanding of DA
      action on GI motility, we used an organ tissue bath system to characterize motor
      function of distal colonic smooth muscle segments from wild-type and DA
      transporter knockout (DAT -/-) mice. In wild-type mice, combined blockade of D(1)
      and D(2) receptors resulted in significant increases in tone (62 +/- 9%),
      amplitude of spontaneous phasic contractions (167 +/- 24%), and electric field
      stimulation (EFS)-induced (40 +/- 8%) contractions, suggesting that endogenous DA
      is inhibitory to mouse distal colonic motility. The amplitudes of spontaneous
      phasic and EFS-induced contractions were lower in DAT -/- mice relative to wild
      type mice. These differences were eliminated by combined D(1) and D(2) receptor
      blockade, indicating that the inhibitory effects of DA on distal colonic motility
      are potentiated in DAT -/- mice. Motility index was decreased but spontaneous
      phasic contraction frequency was enhanced in DAT -/- mice relative to wild-type
      mice. The fact that spontaneous phasic and EFS-induced contractile activity were
      altered by the lack of the DA transporter suggests an important role for
      endogenous DA in modulating motility of mouse distal colon.

PMID- 10915640
TI  - Altered intestinal transport of amino acids in cirrhotic rats: the effect of
      insulin-like growth factor-I.
AB  - The intestine is an important target organ for insulin-like growth factor-I (IGF
      I), an anabolic hormone synthesized in the liver upon growth hormone (GH)
      stimulation. Levels of IGF-I are reduced in cirrhosis, and altered GH/IGF-I axis
      may contribute to malnutrition in cirrhotic patients. Our aim was to study Na(+)
      dependent jejunal transport of amino acids (L-leucine, L-proline, L-glutamic
      acid, and L-cysteine) in cirrhotic rats and to analyze the effect of IGF-I on
      this function. IGF-I or saline was administered for 2 wk to rats with CCl(4)
      induced cirrhosis and saline was administered to healthy control rats. Transport
      of amino acids was assessed in brush-border membrane vesicles (BBMV) using (14)C-
      or (35)S-labeled amino acids, and the kinetic constants V(max) and K(t) were
      determined. Na(+)-independent uptake of L-leucine, L-proline, L-glutamic acid,
      and L-cysteine by BBMV was similar in all groups. Na(+)-dependent uptake of all
      four amino acids was significantly diminished in cirrhotic rats compared with
      both controls and IGF-I-treated cirrhotic rats. The latter two groups exhibited
      similar V(max) and K(t), whereas untreated cirrhotic rats had reduced V(max) and
      increased K(t) compared with normal controls and IGF-I-treated cirrhotic animals.
      In conclusion, the transport of all four tested amino acids by BBMV is impaired
      in cirrhotic rats, and low doses of IGF-I can correct this defect.

PMID- 10915641
TI  - Lymphatic absorption of fatty acids and cholesterol in the neonatal rat.
AB  - High-fat diets are essential in suckling animals to ensure adequate calories for
      postnatal growth, but their lymphatic transport of dietary lipids has not been
      characterized. We established a lymph fistula model in suckling rats to quantify
      intestinal uptake and lymphatic transport of dietary lipids and analyzed
      lipoprotein fractions. Suckling 19-day-old Sprague-Dawley rats had their
      mesenteric lymph ducts cannulated and gastroduodenal tubes inserted. After
      overnight recovery, [(3)H]triolein and [(14)C]cholesterol were infused for 6 h.
      Of the total dose, only 38% of triolein and 24% of cholesterol were transported
      in the lymph of suckling rats. Analyses of residual luminal contents and
      intestinal mucosal homogenate showed neither reduced absorption nor delayed
      mucosal processing of ingested lipids to be the cause. Thin-layer chromatographic
      analysis of radioactive mucosal lipids, however, showed a predominance of free
      fatty acids (60%) and free cholesterol (67%), implying impaired esterification
      capacity in these animals. We speculate that this reduced esterification allows
      for portal transport or direct enterocyte metabolism of dietary lipids.

PMID- 10915642
TI  - Glutathione oxidation and PTPase inhibition by hydrogen peroxide in Caco-2 cell
      monolayer.
AB  - The role of H(2)O(2) and protein thiol oxidation in oxidative stress-induced
      epithelial paracellular permeability was investigated in Caco-2 cell monolayers.
      Treatment with a H(2)O(2) generating system (xanthine oxidase + xanthine) or
      H(2)O(2) (20 microM) increased the paracellular permeability. Xanthine oxidase
      induced permeability was potentiated by superoxide dismutase and prevented by
      catalase. H(2)O(2)-induced permeability was prevented by ferrous sulfate and
      potentiated by deferoxamine and 1,10-phenanthroline. GSH, N-acetyl-L-cysteine,
      dithiothreitol, mercaptosuccinate, and diethylmaleate inhibited H(2)O(2)-induced
      permeability, but it was potentiated by 1,3-bis(2-chloroethyl)-1-nitrosourea.
      H(2)O(2) reduced cellular GSH and protein thiols and increased GSSG. H(2)O(2)
      mediated reduction of GSH-to-GSSG ratio was prevented by ferrous sulfate, GSH, N
      acetyl-L-cysteine, diethylmaleate, and mercaptosuccinate and potentiated by 1,10
      phenanthroline and 1, 3-bis(2-chloroethyl)-1-nitrosourea. Incubation of soluble
      fraction of cells with GSSG reduced protein tyrosine phosphatase (PTPase)
      activity, which was prevented by coincubation with GSH. PTPase activity was also
      lower in H(2)O(2)-treated cells. This study indicates that H(2)O(2), but not
      O(2)(-). or.OH, increases paracellular permeability of Caco-2 cell monolayer by a
      mechanism that involves oxidation of GSH and inhibition of PTPases.

PMID- 10915643
TI  - Endothelial nitric oxide synthase modulates gastric ulcer healing in rats.
AB  - Nitric oxide has been shown to be beneficial for gastric ulcer healing. We
      determined the relative effects of endothelial and inducible nitric oxide
      synthases on gastric ulcer healing in rats. Ulcers were induced by serosal
      application of acetic acid. Ulcer severity, angiogenesis, and nitric oxide
      synthase expression were assessed 3-10 days later. The effects of inhibitors of
      nitric oxide synthase were also examined. Inducible nitric oxide synthase mRNA
      was only detected in ulcerated tissue (maximal at day 3), whereas the endothelial
      isoform mRNA was detected in normal tissue and increased during ulcer healing.
      Inducible nitric oxide synthase was expressed in inflammatory cells in the ulcer
      bed, whereas endothelial nitric oxide synthase was found in the vascular
      endothelium and in some mucosal cells in both normal and ulcerated tissues.
      Angiogenesis changed in parallel with endothelial nitric oxide synthase
      expression. N(6)-(iminoethyl)-L-lysine did not affect angiogenesis or ulcer
      healing, while N(G)-nitro-L-arginine methyl ester significantly reduced both. In
      conclusion, endothelial nitric oxide synthase, but not the inducible isoform,
      plays a significant role in gastric ulcer healing.

PMID- 10915644
TI  - Divergent homeobox gene hex regulates promoter of the Na(+)-dependent bile acid
      cotransporter.
AB  - The divergent homeobox gene Hex is expressed in both developing and mature liver.
      A putative Hex binding site was identified in the promoter region of the liver
      specific Na(+)-bile acid cotransporter gene (ntcp), and we hypothesized that Hex
      regulates the ntcp promoter through this site. Successive 5'-deletions of the
      ntcp promoter in a luciferase reporter construct transfected into Hep G2 cells
      confirmed a Hex response element (HRE) within the ntcp promoter (nt -733/-714).
      Moreover, p-CMHex transactivated a heterologous promoter construct containing HRE
      multimers (p4xHRELUC), whereas a 5-bp mutation of the core HRE eliminated
      transactivation. A dominant negative form of Hex (p-Hex-DN) suppressed basal
      luciferase activity of p-4xHRELUC and inhibited activation of this construct by p
      CMHex. Interestingly, p-CMHex transactivated the HRE in Hep G2 cells but not in
      fibroblast-derived COS cells, suggesting the possibility that Hex protein
      requires an additional liver cell-specific factor(s) for full activity.
      Electrophoretic mobility shift assays confirmed that liver and Hep G2 cells
      contain a specific nuclear protein that binds the native HRE. We have
      demonstrated that the liver-specific ntcp gene promoter is the first known target
      of Hex and is a useful tool for evaluating function of the Hex protein.

PMID- 10915645
TI  - Role of apolipoprotein D in the transport of bilirubin in plasma.
AB  - Apolipoprotein D (apo D) is a 30-kDa glycoprotein of unknown function that is
      associated with high-density lipoproteins (HDL). Because unconjugated bilirubin
      has been shown to bind apo D with a 0. 8:1 stoichiometry, we examined the
      contribution of this protein to transport of bilirubin in human plasma. Density
      gradient centrifugation analysis using physiological concentrations of
      [(14)C]bilirubin reveals that 9% of unconjugated bilirubin is associated with
      HDL, with the remaining pigment bound primarily to serum proteins (i.e.,
      albumin). The percentage of total plasma bilirubin bound to HDL was found to
      increase proportionally with bilirubin concentration. Affinity of human apo D for
      bilirubin was determined by steady-state fluorescence quenching, with Scatchard
      analysis demonstrating a single binding site for unconjugated bilirubin with an
      affinity constant (K(a)) of approximately 3 x 10(7) M(-1). Incorporation of apo D
      into phosphatidylcholine vesicles had no effect on K(a), suggesting that a lipid
      environment does not alter the affinity of the protein for bilirubin. Using
      stopped-flow techniques, the first-order rate constant for bilirubin dissociation
      from apo D was measured at 5.4 s(-1) (half-time = 129 ms). Our findings indicate
      that HDL is the principal nonalbumin carrier of bilirubin in human plasma and
      further support the proposition that the affinity of HDL for bilirubin is
      primarily the result of binding to apo D.

PMID- 10915646
TI  - EAAT1 is involved in transport of L-glutamate during differentiation of the Caco
      2 cell line.
AB  - Little is known concerning the expression of amino acid transporters during
      intestinal epithelial cell differentiation. The transport mechanism of L
      glutamate and its regulation during the differentiation process were investigated
      using the human intestinal Caco-2 cell line. Kinetic studies demonstrated the
      presence of a single, high-affinity, D-aspartate-sensitive L-glutamate transport
      system in both confluent and fully differentiated Caco-2 cells. This transport
      was clearly Na(+) dependent, with a Hill coefficient of 2. 9 +/- 0.3, suggesting
      a 3 Na(+)-to-1 glutamate stoichiometry and corresponding to the well
      characterized X(A,G)(-) system. The excitatory amino acid transporter (EAAT)1
      transcript was consistently expressed in the Caco-2 cell line, whereas the
      epithelial and neuronal EAAT3 transporter was barely detected. In contrast with
      systems B(0) and y(+), which have previously been reported to be downregulated
      when Caco-2 cells stop proliferating, L-glutamate transport capacity was found to
      increase steadily between day 8 and day 17. This increase was correlated with the
      level of EAAT1 mRNA, which might reflect an increase in EAAT1 gene transcription
      and/or stabilization of the EAAT1 transcript.

PMID- 10915647
TI  - Esophageal tone in patients with total aperistalsis: gastroesophageal reflux
      disease versus achalasia.
AB  - We have evaluated esophageal tone in two different conditions that, in some
      cases, similarly impair phasic esophageal motility. Studies were performed in 14
      healthy volunteers, 10 patients with total esophageal aperistalsis secondary to
      gastroesophageal reflux disease (GERD), and 25 untreated achalasia patients. We
      quantified esophageal compliance and relaxation induced by a nitric oxide donor
      using a barostat. Intraesophageal volume at a minimal distending pressure (2
      mmHg) was not significantly different among all three groups (4.1 +/- 0.7, 3.8 +/
      0.7, and 4.2 +/- 1.2 ml for healthy, GERD, and achalasia groups, respectively).
      Esophageal compliance was significantly increased (P < 0.05 vs. healthy group) in
      the two groups of patients with aperistalsis (1.9 +/- 0.2, 3.0 +/- 0.2, and 3.1
      +/- 0.3 ml/mmHg for healthy, GERD, and achalasia groups, respectively).
      Esophageal relaxation was decreased in GERD patients (Delta diameter: 0.4 +/- 0.1
      cm) and increased in achalasia patients (Delta diameter: 1.3 +/- 0.4 cm) relative
      to healthy subjects (Delta diameter: 0.9 +/- 0.2 cm) (P < 0.05 for GERD vs.
      achalasia and healthy groups). Our results indicate that diseases that similarly
      impair phasic esophageal motility may affect esophageal tone differently.

PMID- 10915648
TI  - Myenteric neurons activate submucosal vasodilator neurons in guinea pig ileum.
AB  - This study examined whether myenteric neurons activate submucosal vasodilator
      pathways in in vitro combined submucosal-myenteric plexus preparations from
      guinea pig ileum. Exposed myenteric ganglia were electrically stimulated, and
      changes in the outside diameter of submucosal arterioles were monitored in
      adjoining tissue by videomicroscopy. Stimulation up to 18 mm from the recording
      site evoked large TTX-sensitive vasodilations in both orad and aborad directions.
      In double-chamber baths, which isolated the stimulating myenteric chamber from
      the recording submucosal chamber, hexamethonium or the muscarinic antagonist 4
      diphenylacetoxy-N-(2-chloroethyl)-piperdine hydrochloride (4-DAMP) almost
      completely blocked dilations when superfused in the submucosal chamber. When
      hexamethonium was placed in the myenteric chamber approximately 50% of responses
      were hexamethonium sensitive in both orad and aboard orientations. The addition
      of 4-DAMP or substitution of Ca(2+)-free, 12 mM Mg(2+) solution did not cause
      further inhibition. These results demonstrate that polysynaptic pathways in the
      myenteric plexus projecting orad and aborad can activate submucosal vasodilator
      neurons. These pathways could coordinate intestinal blood flow and motility.

PMID- 10915649
TI  - Vagal inhibition in the antral region of guinea pig stomach.
AB  - The effects of vagal stimulation in the presence of a muscarinic antagonist were
      examined on three distinct rhythmically active cells located in guinea pig
      antrum. Vagal stimulation inhibited contractions of the circular muscle layer but
      did not change their rate of occurrence. With the use of intracellular recording
      techniques, these stimuli were found to initiate inhibitory junction potentials
      in the circular layer but produced smaller potential changes in driving and
      follower cells. Inhibition of the circular muscle layer involved two separate
      components. The dominant component was independent of changes in membrane
      potential and was abolished by nitro-L-arginine. After abolishing Ca(2+) entry
      into smooth muscle cells with a Ca(2+) antagonist, vagal stimulation continued to
      inhibit the residual contractions associated with each slow wave. When the cyclic
      changes in intracellular Ca(2+) concentration associated with each slow wave were
      measured, they were found to be unchanged by vagal stimulation. The observations
      suggest that vagal inhibition of stomach movements does not alter pacemaker
      activity in the stomach; rather, it results from a change in the sensitivity of
      smooth muscle contractile proteins to Ca(2+).

PMID- 10915650
TI  - NH(4)Cl inhibition of acid secretion: possible involvement of an apical K(+)
      channel in bullfrog oxyntic cells.
AB  - This study was undertaken to determine the mechanism by which ammonium chloride
      (NH(4)Cl) inhibits stimulated acid secretion in the bullfrog gastric mucosa. To
      this end, four possible pathways of inhibition were studied: 1) blockade of
      basolateral K(+) channel, 2) blockade of ion transport activity, 3)
      neutralization of secreted H(+) in the luminal solution, or 4) ATP depletion.
      Addition of nutrient 10 mM NH(4)Cl (calculated NH(3) concentration = 92.5 microM
      and NH(4)(+) concentration = 9.91 mM) inhibited acid secretion within 30 min.
      Inhibition of acid secretion did not occur by blockade of basolateral K(+)
      channel activity or ion transport activity or by neutralization of the luminal
      solution. Although ATP depletion occurred in the presence of NH(4)Cl, the
      magnitude of ATP depletion in 30 min was not sufficient to inhibit stimulated
      acid secretion. By comparing the effect of NH(4)Cl on the resistance of inhibited
      or stimulated tissues, we demonstrate that NH(4)Cl acts specifically on
      stimulated tissues. We propose that NH(4)Cl blocks activity of an apical K(+)
      channel present in stimulated oxyntic cells. Our data suggest that the activity
      of this channel is important for the regulation of acid secretion in bullfrog
      oxyntic cells.

PMID- 10915651
TI  - Effects of M1 and CCK antagonists on latency of pancreatic amylase response to
      intestinal stimulants.
AB  - In six conscious dogs with gastric and duodenal cannulas, secretin (164 pmol. kg(
      1). h(-1) iv) was given to provide a flow of pancreatic juice of approximately 1
      drop/s. Amylase activity was measured in each drop before and after rapid
      intravenous injection of caerulein (7.4 pmol/kg) or intraduodenal injection of L
      tryptophan (1 mmol), sodium oleate (3 mmol), and HCl (3 mmol). All experiments
      were repeated in the presence of the M1 receptor antagonist telenzepine (81 nmol.
      kg(-1). h(-) iv) and the cholecystokinin (CCK) receptor antagonist L-364718 (0.1
      mg/kg iv). Latency of amylase response (time between injection of stimulant and
      sustained increase in amylase activity greater than mean + 3 SD of prestimulatory
      activity) to tryptophan (17 +/- 7 s; n = 6) and oleate (16 +/- 5 s) was
      significantly (P < 0.05) shorter than to caerulein (28 +/- 4 s) and HCl (120 +/-
      47 s). Telenzepine significantly increased the latency of amylase response to
      tryptophan and oleate by >10-fold but not the latency to caerulein or HCl. L
      364718 abolished the amylase response to all stimulants. These findings indicate
      that the early amylase response to intraduodenal tryptophan and oleate is
      mediated by a neural enteropancreatic reflex ending on M1 receptors rather than
      by hormone release. However, the activation of (possibly vagal) CCK receptors is
      essential to run the reflex. The early amylase response to intraduodenal HCl is
      probably mediated by the release of CCK into the blood circulation.

PMID- 10915652
TI  - ATP-dependent GSH and glutathione S-conjugate transport in skate liver: role of
      an Mrp functional homologue.
AB  - Multidrug resistance-associated proteins 1 and 2 (Mrp1 and Mrp2) are thought to
      mediate low-affinity ATP-dependent transport of reduced glutathione (GSH), but
      there is as yet no direct evidence for this hypothesis. The present study
      examined whether livers from the little skate (Raja erinacea) express an Mrp2
      homologue and whether skate liver membrane vesicles exhibit ATP-dependent GSH
      transport activity. Antibodies directed against mammalian Mrp2-specific epitopes
      labeled a 180-kDa protein band in skate liver plasma membranes and stained
      canaliculi by immunofluorescence, indicating that skate livers express a
      homologous protein. Functional assays of Mrp transport activity were carried out
      using (3)H-labeled S-dinitrophenyl-glutathione (DNP-SG). DNP-SG was accumulated
      in skate liver membrane vesicles by both ATP-dependent and ATP-independent
      mechanisms. ATP-dependent DNP-SG uptake was of relatively high affinity
      [Michaelis-Menten constant (K(m)) = 32 +/- 9 microM] and was cis-inhibited by
      known substrates of Mrp2 and by GSH. Interestingly, ATP-dependent transport of
      (3)H-labeled S-ethylglutathione and (3)H-labeled GSH was also detected in the
      vesicles. ATP-dependent GSH transport was mediated by a low-affinity pathway
      (K(m) = 12 +/- 2 mM) that was cis-inhibited by substrates of the Mrp2 transporter
      but was not affected by membrane potential or pH gradient uncouplers. These
      results provide the first direct evidence for ATP-dependent transport of GSH in
      liver membrane vesicles and support the hypothesis that GSH efflux from mammalian
      cells is mediated by members of the Mrp family of proteins.

PMID- 10915653
TI  - Low glutathione peroxidase activity in Gpx1 knockout mice protects jejunum crypts
      from gamma-irradiation damage.
AB  - Gpx1 knockout (KO) mice had a higher number of regenerating crypts in the jejunum
      than did Gpx2-KO or wild-type mice analyzed 4 days after > or =10 Gy gamma
      irradiation. Without gamma-irradiation, glutathione peroxidase (GPX) activity in
      the jejunal and ileal epithelium of Gpx1-KO mice was <10 and approximately 35%,
      respectively, of that of the wild-type mice. Four days after exposure to 11 Gy,
      GPX activity in wild-type and Gpx1-KO ileum was doubled and tripled,
      respectively. However, jejunal GPX activity was not changed. Thus the lack of GPX
      activity in the jejunum is associated with better regeneration of crypt
      epithelium after radiation. Gpx2 gene expression was solely responsible for the
      increase in GPX activity in the ileum, since radiation did not alter GPX activity
      in Gpx2-KO mice. The intestinal Gpx2 mRNA levels of Gpx1-KO and wild-type mice
      increased up to 14- and 7-fold after radiation, respectively. Although the Gpx1
      KO jejunum had higher levels of PGE(2) than the wild-type jejunum after exposure
      to 0 or 15 Gy, these differences were not statistically significant. Thus whether
      GPX inhibits PG biosynthesis in vivo remains to be established. We can conclude
      that the Gpx2 gene compensates for the lack of Gpx1 gene expression in the ileal
      epithelium. This may have abolished the protective effect in Gpx1-KO mice against
      the radiation damage in the ileum.

PMID- 10915654
TI  - Dynamic regulation of mucus gel thickness in rat duodenum.
AB  - We examined the dynamic regulation of mucus gel thickness (MGT) in vivo in rat
      duodenum in response to luminal acid, cyclooxygenase (COX) inhibition, and
      exogenous PGE(2). An in vivo microscopic technique was used to measure MGT with
      fluorescent microspheres in urethan-anesthetized rats. Duodenal mucosa was
      topically superfused with pH 7.0 or pH 2.2 solutions with or without PGE(2) and
      indomethacin treatments. Glycoprotein concentration of duodenal loop perfusates
      was measured with periodic acid/Schiff (PAS) or Alcian blue (AB) staining. MGT
      and perfusate glycoprotein concentration were stable during a 35-min perfusion
      with pH 7.0 solution. Acid exposure increased MGT and PAS- and AB-positive
      perfusate glycoprotein concentrations. Indomethacin pretreatment increased both
      PAS- and AB-positive perfusate glycoprotein at baseline; subsequent acid
      superfusion decreased perfusate glycoproteins and gel thickness. PGE(2) (1 mg/kg
      iv) simultaneously increased MGT and PAS-positive perfusate glycoprotein
      concentrations followed by a transient increase in AB-positive glycoprotein
      concentration, suggesting contributions from goblet cells and Brunner's glands.
      Parallel changes in MGT and perfusate glycoprotein concentration in response to
      luminal acid and PGE(2) suggest that rapid MGT variations reflect alterations in
      the balance between mucus secretion and exudation, which in turn are regulated by
      a COX-related pathway. Luminal acid and PGE(2) augment mucus secretion from
      goblet cells and Brunner's glands.

PMID- 10915656
TI  - Impact of intrinsic blood flow regulation in cirrhosis: maintenance of hepatic
      arterial buffer response.
AB  - The hepatic arterial buffer response (HABR) effectively controls total blood
      perfusion in normal livers, but little is known about blood flow regulation in
      cirrhosis. We therefore studied the impact of HABR on blood perfusion of
      cirrhotic livers in vivo. After 8-wk CCl(4) treatment to induce cirrhosis, 18
      anesthetized rats (and 18 noncirrhotic controls) were used to simultaneously
      assess portal venous and hepatic arterial inflow with miniaturized ultrasonic
      flow probes. Stepwise hepatic arterial blood flow (HAF) or portal venous blood
      flow (PVF) reduction was performed. Cirrhotic livers revealed a significantly
      reduced total hepatic blood flow (12.3 +/- 0.9 ml/min) due to markedly diminished
      PVF (7.3 +/- 0.8 ml/min) but slightly increased HAF (5.0 +/- 0.6 ml/min) compared
      with noncirrhotic controls (19.0 +/- 1.6, 15.2 +/- 1.3, and 3.8 +/- 0.4 ml/min).
      PVF reduction caused a significant HABR, i.e., increase of HAF, in both normal
      and cirrhotic livers; however, buffer capacity of cirrhotic livers exceeded that
      of normal livers (P < 0.05) by 1. 7- to 4.5-fold (PVF 80% and 20% of baseline).
      Persistent PVF reduction for 1, 2, and 6 h demonstrated constant HABR in both
      groups. Furthermore, HABR could be repetitively provoked, as analyzed by
      intermittent PVF reduction. HAF reduction did not induce changes of portal flow
      in either group. Because PVF is reduced in cirrhosis, the maintenance of HAF and
      the preserved HABR must be considered as a protective effect on overall hepatic
      circulation, counteracting impaired nutritive blood supply via the portal vein.

PMID- 10915655
TI  - Gastric acid secretion in aquaporin-4 knockout mice.
AB  - The aquaporin-4 (AQP4) water channel has been proposed to play a role in gastric
      acid secretion. Immunocytochemistry using anti-AQP4 antibodies showed strong AQP4
      protein expression at the basolateral membrane of gastric parietal cells in wild
      type (+/+) mice. AQP4 involvement in gastric acid secretion was studied using
      transgenic null (-/-) mice deficient in AQP4 protein. -/- Mice had grossly normal
      growth and appearance and showed no differences in gastric morphology by light
      microscopy. Gastric acid secretion was measured in anesthetized mice in which the
      stomach was luminally perfused (0. 3 ml/min) with 0.9% NaCl containing
      [(14)C]polyethylene glycol ([(14)C]PEG) as a volume marker. Collected effluent
      was assayed for titratable acid content and [(14)C]PEG radioactivity. After 45
      min baseline perfusion, acid secretion was stimulated by pentagastrin (200
      microg. kg(-1). h(-1) iv) for 1 h or histamine (0.23 mg/kg iv) + intraluminal
      carbachol (20 mg/l). Baseline gastric acid secretion (means +/- SE, n = 25) was
      0.06 +/- 0.03 and 0.03 +/- 0.02 microeq/15 min in +/+ and -/- mice, respectively.
      Pentagastrin-stimulated acid secretion was 0.59 +/- 0.14 and 0.70 +/- 0.15
      microeq/15 min in +/+ and -/- mice, respectively. Histamine plus carbachol
      stimulated acid secretion was 7.0 +/- 1.9 and 8.0 +/- 1.8 microeq/15 min in +/+
      and -/- mice, respectively. In addition, AQP4 deletion did not affect gastric
      fluid secretion, gastric pH, or fasting serum gastrin concentrations. These
      results provide direct evidence against a role of AQP4 in gastric acid secretion.

PMID- 10915658
TI  - Keep looking: satisfaction of search.

PMID- 10915659
TI  - Endovascular repair of abdominal aortic aneurysms: current status and future
      directions.

PMID- 10915660
TI  - Imaging-guided microsurgery and the future of radiology.

PMID- 10915661
TI  - Effect of reorganization on patient care.

PMID- 10915662
TI  - Radiology 1999: survival of excellence.

PMID- 10915657
TI  - Colon water transport in transgenic mice lacking aquaporin-4 water channels.
AB  - Transgenic null mice were used to test the hypothesis that water channel
      aquaporin-4 (AQP4) is involved in colon water transport and fecal dehydration.
      AQP4 was immunolocalized to the basolateral membrane of colonic surface
      epithelium of wild-type (+/+) mice and was absent in AQP4 null (-/-) mice. The
      transepithelial osmotic water permeability coefficient (P(f)) of in vivo perfused
      colon of +/+ mice, measured using the volume marker (14)C-labeled polyethylene
      glycol, was 0.016 +/- 0.002 cm/s. P(f) of proximal colon was greater than that of
      distal colon (0.020 +/- 0.004 vs. 0. 009 +/- 0.003 cm/s, P < 0.01). P(f) was
      significantly lower in -/- mice when measured in full-length colon (0.009 +/-
      0.002 cm/s, P < 0. 05) and proximal colon (0.013 +/- 0.002 cm/s, P < 0.05) but
      not in distal colon. There was no difference in water content of cecal stool from
      +/+ vs. -/- mice (0.80 +/- 0.01 vs. 0.81 +/- 0.01), but there was a slightly
      higher water content in defecated stool from -/- mice (0.68 +/- 0.01 vs. 0.65 +/-
      0.01, P < 0.05). Despite the differences in water permeability with AQP4
      deletion, theophylline-induced secretion was not impaired (50 +/- 9 vs. 51 +/- 8
      microl. min(-1). g(-1)). These results provide evidence that transcellular water
      transport through AQP4 water channels in colonic epithelium facilitates
      transepithelial osmotic water permeability but has little or no effect on colonic
      fluid secretion or fecal dehydration.

PMID- 10915663
TI  - Centennial photo page. Silicosis and a few of the other pneumoconiosies:
      observations on certain aspects of the problem, with emphasis on the role of the
      radiologist. 1958.

PMID- 10915664
TI  - The radiologist and occupational lung disease: an appeal for continued
      involvement.

PMID- 10915665
TI  - Is being sued for malpractice grounds for dismissal from a residency program ?

PMID- 10915666
TI  - Customer service and satisfaction in radiology.

PMID- 10915667
TI  - Creating a digital radiographic teaching file and database using a PC and common
      software.
AB  - OBJECTIVE: We wanted to design an inexpensive, convenient database to store
      digital radiographic images of multiple formats. CONCLUSION: We designed a
      database that could be saved in a standard format using readily available
      software. Users of our database can save images in a Joint Photographic Experts
      Group (JPEG) format, allowing their easy incorporation into other programs.

PMID- 10915668
TI  - Helical CT of urinary calculi: effect of stone composition, stone size, and scan
      collimation.
AB  - OBJECTIVE: Helical CT has become the preferred methodology for identifying
      urinary calculi. However, the ability to predict stone composition, which
      influences patient treatment, depends on the accurate measurement of the
      radiographic attenuation of stones. We studied the effects of stone composition,
      stone size, and scan collimation width on the measurement of attenuation in
      vitro. MATERIALS AND METHODS: One hundred twenty-seven human urinary calculi of
      known composition and size were scanned at 120 kVp, 240 mA, and a 1:1 pitch at
      different collimations. A model, based on the physics of helical CT, was used to
      predict the effect of scan collimation width and stone size on measured
      attenuation. RESULTS: At a 1-mm collimation, stone groups could be differentiated
      by attenuation: the attenuation of uric acid was less than that of cystine or
      struvite, which overlapped; these were less than the attenuation of calcium
      oxalate monohydrate, which was in turn lower than that of brushite and
      hydroxyapatite, which overlapped and showed the highest values. At a wider
      collimation, attenuation was lower and the ability to differentiate stone
      composition was lost. Attenuation also decreased with smaller stones. At a 10-mm
      collimation, some uric acid stones (<approximately 6 mm) and other stones (<
      approximately 4 mm) had very low attenuation, so low that they could remain
      undetected on helical CT. The model predicted well the degree that attenuation
      was affected by stone size and collimation width. CONCLUSION: Stone composition
      and stone size, relative to CT collimation, independently influenced CT
      attenuation. The effect of stone size and collimation generally conformed to the
      model's predictions. We determined that small stones with low attenuation can be
      overlooked on helical CT.

PMID- 10915669
TI  - Sensitivity of CT scout radiography and abdominal radiography for revealing
      ureteral calculi on helical CT: implications for radiologic follow-up.
AB  - OBJECTIVE: We compared the sensitivity of CT scout radiography with that of
      abdominal radiography in revealing ureteral calculi on unenhanced helical CT.
      MATERIALS AND METHODS: Over a 6-month period, patients presenting to the
      emergency department with acute flank pain were examined with standard abdominal
      radiography and unenhanced helical CT, which included CT scout radiography. In 60
      patients in whom a diagnosis of ureteral calculus was made, CT scout radiographs
      and abdominal radiographs were examined by two interpreters who assessed whether
      stones could be visualized. All CT scout radiographs were viewed on a workstation
      using optimized window settings. RESULTS: CT scout radiography and abdominal
      radiography revealed 28 (47%) and 36 (60%) of 60 ureteral calculi, respectively.
      All ureteral calculi that appeared on CT scout radiography also appeared on
      abdominal radiography. However, eight calculi that were visible on abdominal
      radiography were not visible on CT scout radiography. CT scout radiography and
      abdominal radiography revealed 28% and 46% of 39 calculi less than or equal to 3
      mm in diameter, respectively. For 21 calculi larger than 3 mm, the sensitivity of
      CT scout radiography and abdominal radiography was 81% and 86%, respectively.
      CONCLUSION: Abdominal radiography is more sensitive than CT scout radiography in
      revealing ureteral calculi; however, some calculi revealed on unenhanced helical
      CT cannot be seen on either abdominal radiography or CT scout radiography.
      Ureteral calculi not visible on either study can only be followed, when
      necessary, with unenhanced helical CT.

PMID- 10915670
TI  - Charles A. Rohrmann, Jr., 2000-2001 distinguished scientist, Armed Forces
      Institute of Pathology.

PMID- 10915672
TI  - Helical CT of prostate cancer: early clinical experience.
AB  - OBJECTIVE: [corrected] This study was undertaken to determine whether helical CT
      can reveal carcinoma of the prostate detected at transrectal sonographically
      guided biopsy. MATERIALS AND METHODS: Helical CT of the prostate was performed in
      35 patients: 25 with proven prostate cancer (group I) and 10 without cancer
      detected at biopsy (group II). All patients in group I had cancer in the
      peripheral zone, and three of these showed foci of cancer in the transitional
      zone. All patients of group II had undergone at least two sets of biopsy before
      CT. In group I, areas of contrast enhancement in the peripheral zone of the
      prostate were defined as suggestive of cancer and correlated with the
      histopathologic findings. RESULTS: Helical CT revealed cancer in 22 (88%) of 25
      patients with proven prostate cancer. Transrectal sonographically guided biopsy
      detected 102 cancer sites in the peripheral zone and three in the transitional
      zone in these 25 patients. Helical CT accurately revealed 59 peripheral zone
      cancer sites (58%) but did not reveal 43 cancer sites (42%). Abnormal contrast
      enhancement in the peripheral zone that was not caused by cancer was seen in 10%
      of suspicious lesions. The three cancer sites in the transitional zone were
      indistinguishable from benign nodular changes. CONCLUSION: Prostate cancer
      detected at transrectal sonographically guided biopsy appears on helical CT of
      the prostate as focal or diffuse areas of contrast enhancement in the peripheral
      zone. A prospective study has been initiated to determine the accuracy,
      sensitivity, and specificity.

PMID- 10915671
TI  - Cystic renal masses: accurate Bosniak classification requires adequate renal CT.
AB  - OBJECTIVE: The objective of this study was to assess the practical usefulness of
      the Bosniak classification system for separating surgical from nonsurgical cystic
      renal masses in a large number of patients examined with properly performed renal
      CT. The study included only patients whose scans were technically adequate to
      allow proper assignment of the lesion to a category. MATERIALS AND METHODS: The
      scans of 109 patients were gathered from two large teaching institutions both
      prospectively and retrospectively, yielding a total of 116 analyzable renal
      cystic lesions. Eighty-two masses were resected from 77 of these patients,
      retrospectively categorized by two experienced uroradiologists using the Bosniak
      classification system, and correlated with pathology reports. A second group of
      34 lesions in 32 patients with atypical cysts was followed up prospectively for
      periods ranging from 3 months to 10 years. RESULTS: The results were similar for
      the two institutions: 15 resected categories I and II lesions were correctly
      identified as benign, and all 18 category IV lesions were malignant. Twenty-nine
      (59%) of 49 pooled category III masses were malignant. No malignancies have been
      identified in the prospectively monitored group of patients. CONCLUSION: Our
      results are compared with earlier, smaller series and support those that show
      that the Bosniak classification system is useful in separating lesions requiring
      surgery from those that can be safely followed up, provided proper CT techniques
      are used.

PMID- 10915674
TI  - Pelvic endometriosis: various manifestations and MR imaging findings.

PMID- 10915673
TI  - Prevalence and significance of heterogeneous testes revealed on sonography: ex
      vivo sonographic-pathologic correlation.
AB  - OBJECTIVE: Heterogeneous or mottled testes in middle-aged or elderly men are
      often encountered on sonography. To determine the prevalence, cause, and
      significance of this finding, we examined 50 testes (25 pairs) from autopsy
      specimens with sonography and gross and microscopic pathology. SUBJECTS AND
      METHODS: Testicles were obtained at autopsy from a series of 25 male cadavers
      (age range, 16-80 years; mean, 62 years). Eight subjects had a history of cancer.
      Ex vivo sonography was performed and two board-certified radiologists graded the
      testis by consensus as normal, heterogeneous, or "other abnormality" (cyst,
      dilated rete, echogenic focus, or halo). Microscopic pathology was obtained in
      all abnormal (sonographic or gross pathologic) testes. The severity of tubular
      sclerosis (atrophy) was graded on a scale of 0-3+ by a uropathologist. RESULTS;
      No testicular tumors were detected. Sonography revealed normal testes in 33
      specimens, heterogeneous in seven specimens, and other in 10 specimens (one cyst,
      two dilated rete, three halos, and seven echogenic foci). Histology revealed that
      all seven cases of mottled or heterogeneous testis corresponded to extensive
      (grades 2 and 3) regions of tubular sclerosis (atrophy). A new sonographic
      finding of the "halo" was attributable to a thickened, adherent tunica albuginea.
      CONCLUSION: The prevalence of heterogeneous testes in this elderly population was
      14% and represented seminiferous tubule atrophy and sclerosis. The prevalence of
      clinically occult testicular cancer or metastases in this autopsy subject group
      was nil. Older patients with a mottled or heterogeneous testis, normal color
      Doppler flow, and no palpable abnormality probably do not need sonographic follow
      up.

PMID- 10915675
TI  - Using the uterine push-pull technique to outline the fundal contour on
      hysterosalpingography.

PMID- 10915676
TI  - The great escape: interfascial decompression planes of the retroperitoneum.

PMID- 10915677
TI  - Intramural tracking: a feature of esophageal intramural pseudodiverticulosis.
AB  - OBJECTIVE: Our purpose was to determine the frequency of intramural tracking in
      patients with esophageal intramural pseudodiverticulosis and to characterize the
      morphologic features of this finding on barium studies. MATERIALS AND METHODS: A
      review of radiology files at two institutions revealed 30 cases of esophageal
      intramural pseudodiverticulosis diagnosed at esophagography. In all cases, the
      radiographs were reviewed retrospectively to determine the frequency and
      morphologic features of intramural tracking in these patients. The number and
      distribution of pseudodiverticula and the presence or absence of strictures or
      esophagitis were also noted. RESULTS: Fifteen (50%) of 30 patients with
      esophageal intramural pseudodiverticulosis had intramural tracking on
      esophagography. The tracks had an average length of 1.2 cm (length range, 0.3-7
      cm) and an average width of 1.6 mm (width range, 1-4 mm). The pseudodiverticula
      were more numerous and had a more diffuse distribution in patients with tracking
      than in patients without tracking. Although patients with and without tracking
      had a similar frequency of strictures and esophagitis, patients with tracking
      were more likely to have strictures involving the upper or mid esophagus, whereas
      patients without tracking were more likely to have strictures in the distal
      esophagus. These findings indicate that intramural tracking is more likely to
      occur in patients with the diffuse form of esophageal intramural
      pseudodiverticulosis. CONCLUSION: Intramural tracking was detected on
      esophagography in 50% of patients with esophageal intramural
      pseudodiverticulosis, so this type of tracking is a more common radiographic
      finding than has previously been recognized. Although intramural tracking has
      little or no known clinical significance, it is important to be aware of this
      finding so that it is not mistaken for a large flat ulcer in the esophagus or for
      an extramural collection associated with esophageal peridiverticulitis.

PMID- 10915678
TI  - Radiologic gastrostomy placement: pigtail- versus mushroom-retained catheters.
AB  - OBJECTIVE: Two different types of percutaneous fluoroscopic gastrostomy
      procedures were prospectively evaluated. SUBJECTS AND METHODS: Between January 1,
      1998, and August 10, 1999, 127 percutaneous gastrostomy catheters were placed in
      128 patients in 128 attempts. Seventy-five 12- or 14-French pigtail-retained
      catheters and fifty-two 20-French mushroom-retained catheters were inserted.
      Catheters were generally placed on the basis of operator preference except
      pigtail-retained tubes were preferentially placed in patients with head and neck
      or esophageal malignancies and mushroom-retained catheters were preferentially
      placed in neurologically compromised or combative patients. The technical
      success, procedural complications, and catheter complications were recorded.
      Statistical analysis was performed. RESULTS: Ninety-nine percent (127/128) of the
      procedures were successful, and there were no procedural complications. One
      catheter was not placed because the colon intervened between the abdominal wall
      and stomach. In patients who received pigtail-retained catheters, the major
      complication rate was 3% (2/75), the minor complication rate was 8% (6/75), and
      the tube complication rate was 36% (27/75). The following complications were
      seen: tube occlusion (n = 12), inadvertent catheter removal (n = 8), peristomal
      tube leakage (n = 7), superficial cellulitis (n = 4), aspiration pneumonia (n =
      2), and T-fastener cellulitis (n = 2). In patients who received mushroom-retained
      catheters, the major complication rate was 0%, the minor complication rate was 2%
      (1/52), and the tube complication rate was 2% (1/52). Complications were
      superficial cellulitis (n = 1) and partial catheter fracture (n = 1). There were
      no significant differences in major and minor complications between procedures.
      Pigtail-retained catheters had a significantly higher rate of tube complications
      (p < 0.001) CONCLUSION: Compared with pigtail-retained catheters, mushroom
      retained gastrostomy catheters are more durable and secure and are less prone to
      tube dysfunction. These catheters should be preferentially placed when possible.

PMID- 10915679
TI  - Venous thrombosis and occlusion after pancreas transplantation: evaluation with
      breath-hold gadolinium-enhanced three-dimensional MR imaging.
AB  - OBJECTIVE: We describe the imaging findings of venous thrombosis and occlusion
      after pancreatic transplantation in five patients who underwent multiphasic
      breath-hold gadolinium-enhanced three-dimensional MR imaging. CONCLUSION: Venous
      thrombus appeared as serpetine voids within the graft parenchyma or at the venous
      anastomosis during the venous phase of MR imaging. Nonenhancement or
      heterogeneous enhancement of graft parenchyma corresponded to glandular necrosis
      at pancreatectomy in two patients. Initial sonographic evaluation was
      nondiagnostic of venous thrombosis in two of five patients. Multiphasic breath
      hold gadolinium-enhanced three-dimensional MR imaging of pancreatic transplants
      can provide information to make the specific diagnosis of venous thrombosis or
      occlusion.

PMID- 10915680
TI  - Imaging of Mycobacterium avium-intracellulare infection in AIDS patients on
      highly active antiretroviral therapy: reversal syndrome.
AB  - OBJECTIVE: We recently encountered six patients with AIDS and an unusual
      complication of disseminated infection with Mycobacterium avium-intracellulare,
      which developed after the initiation of highly active antiretroviral therapy,
      including protease inhibitors and two new nucleoside analogues. Each patient had
      a febrile illness after the initiation of therapy and then developed mass lesions
      containing mycobacterial organisms in various organ systems, including bone,
      skin, and mesenteric and mediastinal nodes. All these patients suddenly
      experienced improvement in immunologic status as evidenced by decreasing viral
      loads and increasing CD4 cell counts. We chose to call this reaction "M. avium
      intracellulare reversal syndrome." We describe the radiologic appearance of this
      unusual manifestation of infection with M. avium-intracellulare in patients with
      AIDS. CONCLUSION: New or enlarging lymphadenopathy or unusual musculoskeletal and
      cutaneous infections in patients with AIDS who are receiving highly active
      antiretroviral therapy may represent a response of the recovering immune system
      to a new or previously subclinical infection with M. avium-intracellulare.

PMID- 10915681
TI  - MR imaging of pneumonia in immunocompromised patients: comparison with helical
      CT.
AB  - OBJECTIVE: A T2-weighted turbo spin-echo sequence was compared with CT in
      immunocompromised patients with opportunistic pneumonia. SUBJECTS AND METHODS:
      Sixteen patients with pneumonia shown on helical CT were examined using MR
      imaging within 2 days. MR examinations were performed on a 1.5-T system with a
      transversal T2-weighted ultrashort turbo spin-echo sequence using expiratory
      gating and diastolic triggering. Two radiologists reviewed the MR and CT images
      independently. The number, localization, and morphology of lesions were noted. MR
      image quality was rated using a 4-point scale. RESULTS: The results of the CT and
      MR examinations concerning the number and morphology of pulmonary lesions caused
      by pneumonia were identical in 75% of the patients (n = 12). MR imaging was able
      to depict all typical features of pneumonia including different stages of
      parenchymal infiltration (ground-glass versus consolidation). MR imaging depicted
      early necrotizing pneumonia not shown on contrast-enhanced CT in 25% of the
      patients (n = 4); 82% of the MR examinations were rated as excellent (1 point) or
      good (2 points). CONCLUSION: T2-weighted turbo spin-echo imaging is able to
      depict characteristic features of pneumonia and shows excellent results compared
      with CT. This MR technique offers advantages in patients with pneumonia because
      of its higher sensitivity for necrotizing pneumonia.

PMID- 10915682
TI  - How well can radiologists using neural network software diagnose pulmonary
      embolism?
AB  - OBJECTIVE: This study evaluated and optimized the performance of an automated
      artificial neural network image interpreter in the diagnosis of pulmonary
      embolism on ventilation-perfusion lung scans. The computer interpretations were
      compared with the interpretations of three experienced observers. MATERIALS AND
      METHODS: Digital data were obtained from 100 patients with normal findings on
      chest radiographs who were undergoing both radionuclide ventilation-perfusion
      scanning and pulmonary angiography. Interpretations of differently trained neural
      networks were compared with those of three experienced nuclear medicine
      practitioners unaware of the clinical diagnosis. RESULTS: Machines running neural
      networks performed similarly to experienced scan interpreters in the detection of
      pulmonary embolism. Both the human observers and the networks performed best in
      cases with large emboli. Neural network performance was best in the right lung,
      when the networks were trained using only cases with large emboli and when
      networks were trained independently in the right and left lungs. The best
      predictions resulted from a collaborative interpretation incorporating both the
      human and computer predictions. CONCLUSION: Computers running artificial neural
      networks using scan data obtained directly from the anterior and posterior
      ventilation and perfusion images, without human involvement, perform comparably
      with experienced observers in patients with normal findings on chest radiographs.
      Human observers can improve their interpretations by incorporating computer
      output to formulate diagnostic prediction. The method of training the networks is
      critical to optimizing performance.

PMID- 10915683
TI  - Clinical value of thin collimation in the diagnostic workup of pulmonary
      embolism.
AB  - OBJECTIVE: We report our experience with thin-collimation helical CT in a
      population of patients suspected of having pulmonary embolism. CONCLUSION: Thin
      collimation helical CT provided technically acceptable examinations for pulmonary
      embolism in 360 patients (97%). In this population, CT revealed pulmonary
      embolism in 104 patients (29%), negative findings in 217 patients (59%),
      indeterminate findings in 39 patients (10%), and alternative diagnoses in 65% of
      patients with negative or inconclusive findings. Ventilation-perfusion scanning
      and Doppler sonography of the lower extremities were performed in 158 (44%) and
      133 patients (37%), respectively, whereas pulmonary angiography was performed in
      27 patients (7.5%). The estimated false-negative rate of helical CT was 5%.

PMID- 10915684
TI  - Venice, italy

PMID- 10915685
TI  - CT findings in 14 patients with Mycobacterium chelonae pulmonary infection.
AB  - OBJECTIVE: The purpose of this report is to describe helical and high-resolution
      CT findings in 14 patients with pulmonary infection caused by Mycobacterium
      chelonae, a nontuberculous mycobacterial species that has become increasingly
      recognized as a rare but significant cause of chronic lung infection in
      immunocompetent patients. CONCLUSION: Bronchiectasis, nodules, and consolidation
      are the most common CT features of M. chelonae pulmonary infection. Cavities are
      less common. These CT findings resemble those reported for Mycobacterium avium
      complex. In this study, M. chelonae pulmonary infection occurred exclusively in
      middle-aged and older women.

PMID- 10915686
TI  - Thoracic outlet: anatomic correlation with MR imaging.
AB  - OBJECTIVE: The purpose of this report is to describe the normal MR anatomy of the
      thoracic outlet and its modification after postural maneuvers using an anatomic
      MR imaging correlation. CONCLUSION: MR imaging appears to be a useful technique
      to study the thoracic outlet and its contents because of its excellent soft
      tissue depiction and its multiplanar capabilities. T1-weighted images obtained in
      the sagittal plane clearly depicted the different compartments of the
      cervicothoracic-brachial junction. Hyperabduction maneuvers may have potential
      applications in the assessment of the thoracic outlet syndrome by showing the
      location of compression.

PMID- 10915687
TI  - Imaging of noncalcified coronary plaques using helical CT with retrospective ECG
      gating.

PMID- 10915689
TI  - Radiation-induced temporal lobe changes: CT and MR imaging characteristics.
AB  - OBJECTIVE: This article documents the CT and MR imaging characteristics of
      patients with temporal lobe changes after radiation therapy for nasopharyngeal
      carcinoma. These characteristics may serve to differentiate radiation-induced
      changes from intracranial tumor recurrence. MATERIALS AND METHODS: We reviewed
      the imaging records of 1916 patients with nasopharyngeal carcinoma examined over
      a 5-year period. Forty-seven patients (2.5%) had temporal lobe changes. Thirty
      four patients underwent CT (55 examinations), and 26 patients underwent MR
      imaging (32 examinations). Thirteen patients underwent CT and MR imaging. These
      studies were independently analyzed according to imaging technique and were
      categorized as follows: location of lesions, characteristics of gray or white
      matter changes, and patterns of late changes. RESULTS: On CT, 12 patients (35%)
      had unilateral temporal lobe changes, and 22 patients (65%) had bilateral
      temporal lobe changes. The following patterns were noted: ill-defined contrast
      enhancement in 27 patients (79%); solid enhancement in six patients (18%); and
      ring enhancement in one patient (3%). On MR imaging, 11 patients (42%) had
      unilateral lesions, and 15 patients (58%) had bilateral lesions. Simultaneous
      gray and white matter lesions were noted in 17 patients (65%), and nine patients
      (35%) had lesions localized to the gray matter. Three patients (6%) had cerebral
      atrophy, and two patients (4%) had encephalomalacia. CONCLUSION: The temporal
      lobes show characteristic CT and MR imaging features after radiation injury.
      Familiarity with these changes may assist in differentiating temporal lobe
      changes from progressive nasopharyngeal carcinoma.

PMID- 10915688
TI  - The effect of aging on the apparent diffusion coefficient of normal-appearing
      white matter.
AB  - OBJECTIVE: The purpose of our study was to test the hypothesis that the apparent
      diffusion coefficient (ADC) of normal-appearing white matter increases with
      advancing age. SUBJECTS AND METHODS: We selected 38 patients with normal MR
      imaging findings from 332 patients undergoing clinical MR imaging. Diffusion
      weighted MR imaging was performed with diffusion gradients applied in three
      orthogonal directions. For each patient, the average ADC on trace-weighted
      diffusion images of white matter at prespecified regions of interest and at the
      thalamus were compared with the patient's age. RESULTS: For the white matter, ADC
      sorted by patient age in decades increased with advancing age. Patients at least
      60 years old had significantly higher ADC (0.769 +/- 0.019 mm(2)/sec x 10(-3))
      than patients less than 60 years old (0.740 +/- 0.013 mm(2)/sec x 10(-3)) (p <
      0.001). Comparison of individual white matter ADC and age showed a significant
      increase with advancing age (p < 0.0001). For the thalamus, the average ADC among
      patients at least 60 years old (0.766 +/- 0.015 mm(2)/sec x 10(-3)) exceeded the
      average ADC for patients less than 60 years old (0.745 +/- 0.022 mm(2)/sec x 10(
      3)) (p < 0.05). However, comparison of individual thalamic ADC and patient ages,
      although showing a trend to higher ADC with increasing age, did not reach
      statistical significance (p = 0.06). CONCLUSION: Advancing age is associated with
      a small but statistically significant increase of water diffusibility in human
      white matter. A similar trend was present in the thalamus. These increases may
      reflect mild structural changes associated with normal aging.

PMID- 10915690
TI  - MR imaging features of Nipah encephalitis.
AB  - OBJECTIVE: The newly discovered Nipah virus causes an acute febrile encephalitic
      illness in humans that is associated with a high mortality. The purpose of this
      study is to describe the MR imaging findings of Nipah encephalitis. MATERIALS AND
      METHODS: MR imaging of the brain was performed in 31 patients with Nipah
      encephalitis divided into three groups. The first group (14 patients) underwent
      MR imaging during the acute phase of the illness and the second group (10
      patients) during the later phase of the acute illness. The third group consisted
      of six patients who underwent MR imaging because they experienced neurologic
      relapse and one patient who had late-onset encephalitis. Spin-echo T1- and T2
      weighted sequences and T2-weighted fluid attenuated inversion recovery (FLAIR)
      sequences were performed. Contrast-enhanced MR imaging was performed in four
      patients. RESULTS: The FLAIR sequences revealed abnormalities in all patients
      studied. MR imaging findings in both the acute and later phases of encephalitis
      were similar; the main feature of both phases was the presence of discrete high
      signal-intensity lesions, measuring 2-7 mm, disseminated throughout the brain,
      mainly in the subcortical and deep white matter of the cerebral hemispheres.
      Neither mass effect nor cerebral edema was seen. There was no correlation with
      the focal neurologic signs, depth of coma, and outcome of the patients. The
      lesions were attributed to widespread microinfarctions from underlying vasculitis
      of cerebral small vessels. Features found on MR imaging in relapsed and late
      onset encephalitis differed from the features in acute encephalitis in that
      confluent cortical involvement was the prominent finding in the former, as
      opposed to discrete focal lesions in the subcortical and deep white matter in the
      latter. CONCLUSION: MR imaging is a sensitive and specific diagnostic tool for
      evaluating Nipah encephalitis.

PMID- 10915691
TI  - CT-guided percutaneous fibrin glue therapy of cerebrospinal fluid leaks in the
      spine after surgery.
AB  - OBJECTIVE: The objective of this study is to assess CT-guided percutaneous
      injection of fibrin glue for the management of cerebrospinal fluid leaks within
      the spine. CONCLUSION: Percutaneous CT-guided placement of fibrin glue can
      provide a treatment option for postoperative cerebrospinal fluid leaks,
      potentially allowing a major surgical procedure to be avoided. However, the
      complication of aseptic meningitis may occasionally result from this procedure.

PMID- 10915692
TI  - Modified four-coil phased array assembly for high-resolution MR imaging of the
      cerebellopontine angle.

PMID- 10915693
TI  - MR digital subtraction angiography for the assessment of cranial arteriovenous
      malformations and fistulas.

PMID- 10915694
TI  - Accuracy of three-dimensional gadolinium-enhanced MR angiography in the
      assessment of extracranial carotid artery disease.
AB  - OBJECTIVE: The purpose of this study was to assess three-dimensional (3D)
      gadolinium-enhanced MR angiography, used alone or in association with duplex
      Doppler sonography, with a fast acquisition time (8 sec) for evaluating the
      extracranial carotid arteries. SUBJECTS AND METHODS: In this prospective study,
      48 successive patients with carotid artery stenoses were examined with 3D
      gadolinium-enhanced MR angiography and 3D time-of-flight MR angiography. Of the
      44 eligible patients, conventional angiography was available in 33 and duplex
      sonography in 27. We used the North American Symptomatic Carotid Endarterectomy
      Trial technique to quantify stenosis on all angiograms, and a 250 cm/sec
      threshold at duplex sonography to diagnose stenoses greater than 70%. Image
      quality of 3D gadolinium-enhanced MR angiography and 3D time-of-flight MR
      angiography was assessed, as well as sensitivity and specificity for each
      technique alone and in combination with duplex sonography. Conventional
      angiography was the gold standard. RESULTS: Three-dimensional gadolinium-enhanced
      MR angiography yielded good image quality in 90% of cases. When used alone, it
      yielded a sensitivity and a specificity of 94% and 85%, respectively, in
      screening stenoses greater than 70% (70-99%). When combined with duplex Doppler
      sonography, it provided a 100% sensitivity and specificity for detection of
      stenoses between 70% and 99% and would have obviated 61% of conventional
      angiography. In comparison, 3D time-of-flight MR angiography used alone yielded a
      sensitivity of 88% and a specificity of 94%. In combination with duplex Doppler
      sonography, its use would have obviated conventional angiography in 74% of cases.
      Three-dimensional gadolinium-enhanced MR angiography provided accurate results in
      the diagnosis of occlusions and ulcers and can visualize distant stenoses.
      CONCLUSION: Used alone, 3D gadolinium-enhanced MR angiography is not accurate
      enough to replace conventional angiography in the evaluation of extracranial
      carotid arteries. In association with duplex Doppler sonography, however, it is
      accurate and may obviate a significant number of conventional angiographic
      examinations.

PMID- 10915695
TI  - Potentially distinctive features of sinonasal inverted papilloma on MR imaging.
AB  - OBJECTIVE: The objective of this study is to describe potentially distinctive MR
      features of sinonasal inverted papilloma and those of coexisting squamous cell
      carcinoma. CONCLUSION: A sinonasal mass with a convoluted cerebriform pattern on
      T2- or enhanced T1-weighted images suggests inverted papilloma as a histologic
      diagnosis. Necrosis in a mass with such an appearance strongly suggests
      coexistent carcinoma.

PMID- 10915696
TI  - Dynamic MR dacryocystography: a new method for evaluating nasolacrimal duct
      obstructions.
AB  - OBJECTIVE: The purpose of this study was to evaluate the clinical performance of
      newly implemented dynamic MR dacryocystography. CONCLUSION: Dynamic MR
      dacryocystography, which requires neither ionizing radiation nor chemical
      contrast media with high viscosity, may be a useful tool for depicting
      nasolacrimal obstructions.

PMID- 10915697
TI  - CT and MR imaging of orbital metastasis from islet cell carcinoma of the
      pancreas.

PMID- 10915698
TI  - Differentiating normal from abnormal inferior thoracic paravertebral soft tissues
      on chest radiography in children.
AB  - OBJECTIVE: The purposes of this investigation were to define the normal
      appearances, define factors that have the potential to influence appearance, and
      establish defined criteria to differentiate normal from abnormal appearances of
      posteroinferior paravertebral soft tissues on chest radiography in children.
      SUBJECTS AND METHODS: Paravertebral soft tissues were evaluated on frontal chest
      radiographs in 23 children with documented abnormalities and 275 children without
      abnormalities in the region. The frequency of visualization, course, width, and
      factors (patient positioning, age, and sex) potentially influencing the
      appearance of paravertebral soft tissues were determined. Inferolateral course
      and width greater than that of the adjacent pedicle were evaluated as criteria
      for abnormality. RESULTS: Only 28% of the children without abnormalities had
      paravertebral soft tissues visualized, and the frequency of visualization
      directly increased with age (p = 0.001). For identification of abnormal cases on
      the left side, width greater than the adjacent pedicle had a sensitivity of 100%
      and a specificity of 98%, and inferolateral course had a sensitivity of 86% and a
      specificity of 95%. Visualization on the right side (n = 5) was always abnormal.
      Six normal cases had a width greater than that of the adjacent pedicle on the
      left side on initial radiographs obtained with supine positioning and met normal
      criteria on repeated radiographs with upright positioning. CONCLUSION: Width
      greater than the adjacent pedicle is the best radiographic criterion for
      differentiation of abnormal from normal left-sided paravertebral soft tissues,
      particularly on radiographs obtained with upright positioning. Identifiable right
      sided paravertebral soft tissue is always abnormal. These criteria are useful
      aids in determining the need for additional imaging, such as CT.

PMID- 10915699
TI  - Successful sonographically guided thrombin injection in an infant with a femoral
      artery pseudoaneurysm.

PMID- 10915700
TI  - A time to live It Up

PMID- 10915701
TI  - Imaging of pediatric tongue abnormalities.

PMID- 10915702
TI  - Retinoblastoma: sonographic findings with pathologic correlation in pediatric
      patients.

PMID- 10915703
TI  - Acute edematous stump appendicitis diagnosed preoperatively on sonography.

PMID- 10915704
TI  - Takayasu's arteritis: assessment of disease activity with contrast-enhanced MR
      imaging.
AB  - OBJECTIVE: The purpose of this study was to evaluate the role of contrast
      enhanced MR imaging in the determination of disease activity in patients with
      Takayasu's arteritis. SUBJECTS AND METHODS: High-resolution contrast-enhanced T1
      weighted spinecho MR imaging using small fields of view (14-20 cm) and thin
      slices (4-5 mm) was performed in 26 patients with Takayasu's arteritis and 16
      healthy subjects. The degree of aortic mural enhancement was assessed by
      measuring signal intensity and by visually estimating it in comparison with that
      of the myocardium. RESULTS: Contrast-enhanced MR imaging showed more enhancement
      of thickened aortic wall compared with myocardium, thus suggesting active
      Takayasu's arteritis on MR imaging in 16 patients. Determination of disease
      activity using contrast-enhanced MR imaging was concordant with clinical findings
      in 23 patients (88.5%). Contrast-enhanced MR findings were concordant with
      laboratory findings in most patients (erythrocyte sedimentation rate in 92.3%
      [24/26] and C-reactive protein in 84.6% [22/26]). The measured signal intensity
      of the aortic wall relative to that of myocardium during the early phase of
      contrast-enhanced MR imaging correlated well with the erythrocyte sedimentation
      rate (r = 0.78, p < 0.005) and with the C-reactive protein level (r = 0.63, p <
      0.005). CONCLUSION: Contrast-enhanced MR imaging provides information about
      disease activity of Takayasu's arteritis, which may be useful in the diagnosis
      and treatment of Takayasu's arteritis.

PMID- 10915705
TI  - Distal arterial flow in patients undergoing upper extremity dialysis shunting: a
      prospective study using doppler sonography.
AB  - OBJECTIVE: The objective of this study was to document changes in the distal
      circulation after creation of a proximal upper extremity dialysis shunt and to
      correlate these findings with the patient's clinical condition. SUBJECTS AND
      METHODS: We prospectively examined 18 patients scheduled for upper extremity
      shunt creation. We used color and spectral Doppler sonography to examine flow in
      the radial and ulnar arteries, noting flow direction and peak systolic velocity.
      After the shunt procedure, we repeated the measurements and correlated them
      statistically with hand symptomatology. RESULTS: Six (33%) of 18 patients were
      symptomatic. The mean peak systolic velocities in the radial and ulnar arteries
      were 52 and 61 cm/sec, respectively, before surgery, and decreased to 12 cm/sec
      after surgery in the radial artery and 44 cm/sec in the ulnar artery. The mean
      percentage of decrease in peak systolic velocity was 77% in the radial artery and
      28% in the ulnar artery. Eight patients showed reversed flow. No statistical
      correlation was found between change in peak systolic velocity values before and
      after surgery and the presence of hand symptoms. Similarly, no correlation was
      found between flow reversal and symptoms. The most consistent factor associated
      with symptoms was diabetes; all symptomatic patients were diabetic, but only 54%
      of the diabetic patients were symptomatic. CONCLUSION: The difference in the peak
      systolic velocities in the radial and ulnar arteries after shunt construction
      does not correlate with symptoms. The hand can tolerate a significant decrease in
      the peak systolic velocity and even flow reversal without symptomatology.

PMID- 10915706
TI  - Cost-effectiveness of percutaneous treatment of iliac artery occlusive disease in
      the United States.
AB  - OBJECTIVE: The costs of percutaneous transluminal angioplasty and stent placement
      for iliac artery occlusive disease in the United States were assessed and the
      cost-effectiveness was evaluated. MATERIALS AND METHODS: Lifetime costs and
      quality-adjusted life expectancy were estimated using a Markov decision model for
      a hypothetic cohort of patients with life-style-limiting claudication caused by
      an iliac artery stenosis for whom a percutaneous intervention was indicated.
      Various percutaneous treatment strategies were evaluated, each consisting of an
      initial intervention followed by a secondary intervention. Procedures considered
      were angioplasty alone and angioplasty with selective stent placement. RESULTS:
      From the perspective of the interventional radiology department, angioplasty with
      selective stent placement costs more than angioplasty alone ($2926 versus $2106).
      Taking into account follow-up costs and procedures for long-term failures, the
      cost differential was reduced because of a lower failure rate of selective stent
      placement ($13,158 versus $12,458, respectively). Treatment strategies using
      angioplasty with selective stent placement (as an initial procedure or including
      reintervention) dominated treatment strategies using angioplasty alone
      (incremental cost-effectiveness ratio was $7,624-8,519 per quality-adjusted life
      year gained). CONCLUSION: Angioplasty with selective stent placement is a cost
      effective treatment strategy compared with angioplasty alone in the treatment of
      intermittent claudication in the United States.

PMID- 10915707
TI  - Arterial pseudostenosis on first-pass gadolinium-enhanced three-dimensional MR
      angiography: new observation of a potential pitfall.
AB  - OBJECTIVE: The purpose of this study was to determine the frequency of apparent
      stenosis of normal aortic branches in patients on first-pass gadolinium-enhanced
      three-dimensional (3D) MR angiography and to reproduce the same phenomenon in a
      pulsatile flow phantom model. CONCLUSION: Apparent stenosis of normal vessels on
      gadolinium-enhanced 3D MR angiography seen on the first-pass acquisition was
      observed in only a small proportion (approximately 2%) of our patients. The
      pseudostenosis was reproducible in the phantom model using rapid injection. A
      stenosis on first-pass images should be interpreted with caution. Confirmation of
      the findings on other sequences, such as the second-pass gadolinium-enhanced 3D
      MR angiography or 3D phase-contrast MR angiography, prevented overdiagnosis of
      significant stenoses.

PMID- 10915708
TI  - Early rethrombosis of clotted hemodialysis grafts: graft salvage achieved with an
      aggressive approach.
AB  - OBJECTIVE: The purpose of this study was to assess the efficacy of repeated
      pulsed spray pharmacomechanical thrombolysis for salvage of early rethrombosis of
      hemodialysis grafts and to identify factors that predict successful outcome.
      MATERIALS AND METHODS: Thirty-four patients with initial successful thrombolysis
      were referred for repeated thrombolysis because of early rethrombosis. Repeated
      thrombolysis occurred within 1 month of initial thrombolysis. Technical success
      and patency rates were calculated. Causes of graft thrombosis and procedural
      modifications were analyzed. RESULTS: The 39 rethrombosed grafts were
      successfully treated using pharmacomechanical thrombolysis, and patients
      underwent subsequent hemodialysis. The underlying flow-limiting stenoses were
      treated with balloon angioplasty using a larger balloon (41%), a same-size
      angioplasty balloon (18%), stent placement (15%), or increased anticoagulation
      (5%). A new stenosis location was discovered in 18%. Mean primary patency was
      80.9 days (2.6 months) and secondary patency was 235.4 days (7.8 months). With
      life table analysis, 1-, 3-, 6-, and 12-month primary patency rates were 72%,
      31%, 23%, and 15%, and secondary patency rates were 77%, 62%, 51%, and 31%,
      respectively. Graft patency rates in our study were compared with our
      institutional historic graft patency rates, with no significant difference noted
      (p = 0.76). No major procedural complications occurred. CONCLUSION: Adequate
      technical success and patency rates for pharmacomechanical thrombolysis occur
      even for hemodialysis grafts that rethrombose within 1 month. After thrombolysis,
      aggressive search for and treatment of additional stenoses are warranted.

PMID- 10915710
TI  - Mechanic and pharmacologic treatment of a saddle embolus to the portal vein after
      liver transplantation and portacaval hemitransposition.

PMID- 10915709
TI  - Efficacy of percutaneous abscess drainage in patients with vancomycin-resistant
      enterococci.
AB  - OBJECTIVE: We reviewed a 4-year experience draining fluid collections infected
      with vancomycin-resistant enterococci to determine the outcome of percutaneous
      intervention in patients with this highly resistant and increasingly common
      organism. MATERIALS AND METHODS: Charts of patients from whom vancomycin
      resistant enterococci had been isolated during percutaneous drainage were
      reviewed to determine patient response to drainage, catheter management, and
      outcome of treatment. RESULTS: Twenty-one patients underwent percutaneous
      drainage of 28 fluid collections from which vancomycin-resistant enterococci were
      isolated, including 16 intraabdominal abscesses, seven biliary or urinary
      obstructions, and five empyemas. The drainage of 27 (96%) of 28 collections were
      technically successful. In seven patients, drainage provided the first isolation
      of vancomycin-resistant enterococci from the patient. Five patients also had
      blood cultures with positive findings for vancomycin-resistant enterococci, and
      14 collections were coinfected with other bacteria or with fungi. Twenty
      collections (71%) or obstructions were successfully treated with percutaneous
      drainage. Drainage was unsuccessful in treating eight collections in seven
      patients. CONCLUSION: Despite high-level antibiotic resistance, fluid collections
      infected with vancomycin-resistant enterococci can be successfully drained
      percutaneously, resulting in a favorable likelihood of recovery for patients.

PMID- 10915711
TI  - Rotatory subluxation and fracture at C1-C2.

PMID- 10915712
TI  - Satisfaction of search in osteoradiology.
AB  - OBJECTIVE: "Satisfaction of search" describes a situation in which the detection
      of one radiographic abnormality interferes with that of others. This phenomenon
      has not been investigated for the interpretation of skeletal radiographs. We
      determined whether satisfaction of search occurs in the interpretation of
      conventional radiographs of the musculoskeletal system. SUBJECTS AND METHODS:
      Twelve volunteers from radiology (10 residents and two staff members) and 13
      volunteers from orthopedic surgery (all residents) were shown in random order 15
      cases in which one abnormality was present and 15 cases in which either two or
      three abnormalities were present. The cases with multiple findings contained a
      total of 19 abnormalities. All cases were selected from the emergency department.
      The volunteers received three scores reflecting their ability to detect
      abnormalities on a single-finding case, at least one abnormality on a multiple
      finding case, and additional findings in cases with multiple abnormalities. The
      scores were compared using the chi-square test with Yates correction. Analysis of
      variance and Bonferroni adjustment were also performed. RESULTS: Among the cases
      with single findings, detection rates averaged 11.25; for the 15 multiple-finding
      cases, the detection rate for one finding averaged 11.72. The difference was not
      statistically significant. Detection rates for the second and third abnormalities
      in the multiple-finding cases were significantly lower, averaging 6.12 (p <
      0.01). CONCLUSION: A significant satisfaction of search effect occurred and was
      operative in the interpretation of radiographs of the musculoskeletal system.

PMID- 10915713
TI  - Do radiologists use the American College of Radiology Musculoskeletal
      Appropriateness Criteria?
AB  - OBJECTIVE: The objective of this study was to determine the proportion of
      radiologists in three different radiology organizations who report using the
      American College of Radiology (ACR) musculoskeletal appropriateness criteria.
      MATERIALS AND METHODS: Radiologists from the Society of Skeletal Radiology,
      Georgia Radiological Society, and Utah Radiological Society were surveyed
      regarding their use of the ACR musculoskeletal appropriateness criteria. The
      surveys were carried out during 1998 and data were collected using written survey
      forms, telephone, and fax. RESULTS: The overall survey response rate was 298
      (64%) of 465. Overall, 30% of respondents reported using the musculoskeletal
      appropriateness criteria. The proportion of respondents who used the
      musculoskeletal criteria was not different across the three organizations or for
      private practice compared with academic radiologists. CONCLUSION: The proportion
      of radiologists who report using the ACR musculoskeletal radiology
      appropriateness criteria is low. This result is consistent with other reports in
      the literature that show little impact on the practice of physicians after the
      distribution of written practice guidelines.

PMID- 10915714
TI  - Avulsion fracture of the base of the fifth metatarsal not seen on conventional
      radiography of the foot: the need for an additional projection.
AB  - OBJECTIVE: To our knowledge, this article is the first to describe a series of
      patients with avulsion fractures of the base of the fifth metatarsal that were
      not seen on conventional radiography using the standard three views of the foot
      but that were seen on radiography of the ankle. CONCLUSION: Because routine
      radiographs of the foot may fail to reveal an avulsion fracture of the base of
      the fifth metatarsal, an additional projection should be obtained to better
      assess this region in the symptomatic patient. The additional view should be an
      anteroposterior radiograph of the ankle that includes the base of the fifth
      metatarsal because this projection has been shown to help in the diagnosis of
      this avulsion fracture.

PMID- 10915715
TI  - Thrombosis of the abdominal aorta in a child after blunt trauma.

PMID- 10915716
TI  - Diffuse adenomatoid tumor of the uterus.

PMID- 10915717
TI  - Angioedema of the small bowel: CT appearance.

PMID- 10915718
TI  - The "Pulvinar" sign in variant Creutzfeldt-Jakob disease.

PMID- 10915719
TI  - Author's correction

PMID- 10915720
TI  - Inflammatory mechanisms and therapeutic strategies for warm hepatic
      ischemia/reperfusion injury.

PMID- 10915721
TI  - The function of alkaline phosphatase in the liver: regulation of intrahepatic
      biliary epithelium secretory activities in the rat.
AB  - We studied the effects of alkaline phosphatase (AP) on the secretory processes of
      the rat intrahepatic biliary epithelium as well as the role of the intrahepatic
      biliary epithelium in the uptake and biliary secretion of exogenous AP. The
      effects of acute and chronic administration of AP on bile secretory parameters
      were investigated in vivo in normal and bile duct ligated (BDL) rats and in vitro
      in isolated rat bile duct units (IBDU). In vivo, acute AP administration
      decreased bile flow and biliary bicarbonate excretion and abolished secretin
      choleresis in BDL rats but not in normal rats. On the contrary, the AP inhibitor,
      levamisole, increased in BDL rat bile flow and biliary bicarbonate excretion. In
      vitro, basal and secretin-stimulated Cl(-)/HCO(3)(-) exchanger activity in IBDU
      was immediately inhibited by AP intraluminal microinjection (apical exposure) but
      only after a prolonged exposure to the basolateral pole. Levamisole increased the
      Cl(-)/HCO(3)(-) exchanger activity of IBDU. A significant basolateral uptake of
      AP occurs in IBDU with a progressive transport to the apical domain. AP chronic
      treatment increased AP and gamma-glutamyltranspeptidase (gamma-GT) activities in
      the intrahepatic bile ducts and hepatocyte canalicular pole, promoted enlargement
      of bile canaliculi, and decreased bile flow and biliary bicarbonate excretion. In
      conclusion, the intrahepatic biliary epithelium plays a role in the uptake and
      biliary secretion of serum AP. AP inhibits the secretory processes of the
      intrahepatic biliary epithelium and induces features of intrahepatic cholestasis
      after chronic administration. These findings indicate that AP plays an active
      role in down-regulating the secretory activities of the intrahepatic biliary
      epithelium.

PMID- 10915722
TI  - Liver transplantation for autoimmune hepatitis: a long-term pathologic study.
AB  - Autoimmune hepatitis (AIH) after liver transplantation (LT) may recur and is
      difficult to diagnose. Our aims were to define the histopathology of and factors
      related to AIH recurrence. Fourteen of 475 patients received LT for AIH; 2 died
      perioperatively. Liver specimens (native and post-LT biopsies) from 12 other
      patients were reviewed and correlated with pre- and post-LT clinical course and
      outcome. Recurrent AIH was seen in 5 of 12 patients, 35 to 280 days post-LT as
      lobular hepatitis with acidophil bodies and lymphoplasmacytic infiltrate.
      Portal/interface hepatitis was seen with disease progression and 2 of 5 patients
      developed cirrhosis. Of 7 nonrecurrent patients, 1 had acquired hepatitis C with
      lobular/portal hepatitis and none developed cirrhosis. Histology suggestive of
      overlap syndrome was seen in 3 of 12 native livers with no effect on post-LT
      course or pathology. High-grade necroinflammation was present in native livers at
      LT in 5 of 5 cases with recurrent AIH and in 1 of 7 without recurrence (P <.01).
      Pre-LT disease duration, donor/recipient gender distribution, HLA studies, and
      rejection episodes did not correlate with AIH recurrence. We conclude that (1)
      recurrent AIH is not uncommon and was seen in 42% of patients with
      lymphoplasmacytic lobular, portal, and interface hepatitis; (2) acidophil bodies
      with lymphoplasmacytic cells are seen in early recurrent AIH; (3) recurrent AIH
      appears at variable time periods post-LT, and the progression is slow; and (4)
      high-grade inflammation in native liver at LT is a strong predictor of recurrent
      AIH.

PMID- 10915723
TI  - A Rho-specific exchange factor Ect2 is induced from S to M phases in regenerating
      mouse liver.
AB  - The ect2 oncogene was originally identified as a transforming complementary DNA
      (cDNA) from mouse epithelial cells in an expression cloning approach and encodes
      a product related to Rho-specific exchange factors and yeast cell cycle
      regulators. To explore the potential role of ect2 in the cell cycle, we examined
      the expression of the ect2 proto-oncogene in a liver regeneration model in mice
      after partial (two thirds) hepatectomy. We found that the expression of the ect2
      transcript and protein were markedly elevated with the onset of DNA synthesis and
      remained elevated during G2 and M phases. The timing of ect2 expression matched
      that of proliferating cell nuclear antigen (PCNA) and partially overlapped cell
      division cycle 2 (Cdc2) expression. In situ hybridization analysis showed that
      ect2 was expressed at a high level in cells undergoing mitosis in regenerating
      liver. Moreover, expression of a dominant negative or an oncogenic mutant of ect2
      in cultured mouse hepatocytes resulted in a large increase in the number of
      binucleated cells. These findings showed that Ect2 is expressed in a cell cycle
      dependent manner during liver regeneration, and suggest that it has an important
      role in the regulation of cytokinesis.

PMID- 10915724
TI  - Hepatocellular carcinoma occurring in nonfibrotic liver: epidemiologic and
      histopathologic analysis of 80 French cases.
AB  - Hepatocellular carcinoma (HCC) occurring in nonfibrotic liver represents a rare,
      ill-defined subgroup of HCC without cirrhosis in which mechanisms of
      hepatocarcinogenesis remain unclear. The aim of our study was to assess
      epidemiological factors and detailed histopathologic changes in the nontumoral
      liver of patients developing such tumors. Of 330 HCCs resected in our institution
      between 1985 and 1998, we retrospectively analyzed 80 cases (53 men, 27 women;
      mean age, 51 +/- 16 years) in which the nontumoral liver showed no (n = 28) or
      minimal (n = 52) portal fibrosis without any septal fibrosis. In the group with
      no portal fibrosis there was no male predominance, and patients were
      significantly younger (44 +/- 19 years vs. 54 +/- 14 years) than those with
      minimal portal fibrosis. Sixty-seven tumors were typical HCCs, 8 were of
      fibrolamellar type, and 5 were hepatocholangiocarcinomas. Mean tumor size was 10
      +/- 5 cm. Risk factors for HCC development were found in 30 patients: hepatitis B
      (n = 17) or C (n = 2) virus infections, alcohol consumption (n = 11), and
      hemochromatosis (n = 1). In the nontumoral liver, periportal and lobular
      necrosis, mild portal inflammation, steatosis, and iron overload were present in
      15%, 57%, 52%, and 54% of cases, respectively. Liver cell changes were noted in
      6%. This study emphasizes the need for strict criteria to classify HCC without
      cirrhosis. HCC in nonfibrotic liver is a distinct subgroup in which nontumoral
      liver shows nonspecific minimal changes without regeneration or premalignant
      lesion. Etiologic factors are often unidentified, although presence of HBV
      infection in 21% suggests a direct oncogenic role of this virus.

PMID- 10915726
TI  - Common and epithelioid variants of hepatic angiomyolipoma exhibit clonal growth
      and share a distinctive immunophenotype.
AB  - Angiomyolipoma represents a rare liver tumor of uncertain histogenesis that is
      commonly considered a hamartoma. A series of 12 hepatic angiomyolipomas,
      including 3 samples of the epithelioid subtype, was analyzed for clonality using
      the human androgen receptor gene locus (HUMARA). Four of 6 informative cases
      revealed monoclonality. The polyclonal pattern in the 2 remaining cases was most
      probably caused by excessive infiltration of inflammatory cells. Monoclonality
      with an identical X-chromosomal inactivation pattern in all nodules was found in
      a multifocal recurrent tumor indicating a metastatic process. Despite the
      morphologic heterogeneity, all tumors displayed an identical immunohistochemical
      labeling pattern. It is concluded that different subtypes of hepatic
      angiomyolipoma exhibit a monoclonal and hence probably neoplastic growth and
      share an identical immunophenotype suitable for their identification even in
      small biopsy specimens. The epithelioid subtype may give rise to intrahepatic
      metastasis.

PMID- 10915725
TI  - Superparamagnetic iron oxide-enhanced magnetic resonance images of hepatocellular
      carcinoma: correlation with histological grading.
AB  - Superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging has
      been used for the detection of hepatic tumors. However, little is known about
      this technique in relation to hepatocellular carcinoma (HCC). The aim of this
      study was to investigate whether SPIO-enhanced MR imaging can be useful in
      assessing histological grades of HCC. The authors studied histologically proven
      tumors including 31 HCCs and 6 dysplastic nodules. The ratio of the Kupffer-cell
      count in the tumorous tissue relative to that in the nontumorous tissue (Kupffer
      cell-count ratio) decreased as HCCs became less well differentiated. The ratio of
      the intensity of the tumorous lesion to that of the nontumorous area on SPIO
      enhanced MR images (SPIO intensity ratio) correlated inversely with Kupffer-cell
      count ratio in HCCs and dysplastic nodules (r = -.826, P <.001) and increased as
      the degree of differentiation of HCCs decreased, indicating that the uptake of
      SPIO in HCCs decreased as the degree of differentiation of HCCs declined. All of
      the dysplastic nodules and some well-differentiated HCCs showed hypointense or
      isointense enhancement, relative to the surrounding liver parenchyma, indicating
      greater or similar uptake of SPIO in the tumor when compared with nontumorous
      areas. These results suggest that SPIO-enhanced MR imaging reflects Kupffer-cell
      numbers in HCCs and dysplastic nodules, and is useful for estimation of
      histological grading in HCCs, although uncertainties persist in differentiating
      dysplastic nodules from well-differentiated HCCs.

PMID- 10915727
TI  - Regulatory mechanisms for transforming growth factor beta as an autocrine
      inhibitor in human hepatocellular carcinoma: implications for roles of smads in
      its growth.
AB  - Transforming growth factor beta (TGF-beta) initiates signaling through
      heteromeric complexes of transmembrane type I and type II serine/threonine kinase
      receptors. Activated TGF-beta type I receptor phosphorylates receptor-regulated
      Smads (2 and 3). Antagonistic Smad 7 forms stable association with the activated
      TGF-beta type I receptor, blocking phosphorylation of receptor-regulated Smads.
      On the other hand, elevated serum concentration of TGF-beta along with resistance
      to its growth-inhibitory effect is commonly observed in human hepatocellular
      carcinoma (HCC) patients. In this study, we investigated the mechanisms of
      resistance to tumor-derived TGF-beta in human HCC and hepatoblastoma-derived cell
      lines, focusing on the roles of receptor-regulated Smads and antagonistic Smad 7.
      HuH-7 and HepG2 cells showed poor response to TGF-beta-mediated growth
      inhibition. Because neutralization of TGF-beta in the medium or blockage of
      signal transduction pathway by inductions of dominant negative Smad 2/3 resulted
      in a stimulation of cell growth, tumor-derived TGF-beta signal acts on cell
      growth negatively. However, Smad 7 induced by TGF-beta negatively regulated Smad
      2 action and rendered most Smad 2 proteins in the cytoplasm. Taken together,
      these results indicate that endogenous TGF-beta-mediated induction of Smad 7
      results in a higher "threshold" for the antiproliferative signals mediated by
      receptor-regulated Smads, and can be involved in reduced responsiveness to the
      cytokine in some human HCC cells.

PMID- 10915728
TI  - Interferon beta prevents recurrence of hepatocellular carcinoma after complete
      resection or ablation of the primary tumor-A prospective randomized study of
      hepatitis C virus-related liver cancer.
AB  - Because hepatocellular carcinoma often recurs after surgical resection or ethanol
      injection therapy, we conducted a prospective randomized controlled trial of
      interferon (IFN) in patients with chronic liver disease caused by hepatitis C
      virus (HCV). Twenty eligible patients with cirrhosis were randomized into two
      groups: 10 patients treated with 6 million units of natural IFN-beta twice a week
      for 36 months and 10 patients without IFN therapy. One patient within the
      treatment group discontinued interferon therapy after 19 months of treatment
      because of a mild degree of retinopathy. None of the patients in either group
      lost HCV-RNA until the end of the observation. Although 7 (70.0%) of 10 patients
      in the nontreatment group showed tumor recurrence, only 1 (10.0%) of 10 patients
      with IFN therapy developed tumor recurrence during a median observation period of
      25.0 months. Cumulative recurrence rates of the treated and untreated groups were
      0% and 62.5% at the end of the first year, and 0% and 100% at the second year,
      respectively (log-rank test, P =.0004). In conclusion, intermittent
      administration of IFN suppressed tumor recurrence after treatment with surgery or
      ethanol injection in patients with HCV-related chronic liver disease.

PMID- 10915729
TI  - Natural history of inoperable hepatocellular carcinoma: estrogen receptors'
      status in the tumor is the strongest prognostic factor for survival.
AB  - Clinical course in hepatocellular carcinoma may be very different. We
      prospectively evaluated 96 patients with hepatocellular carcinoma unsuitable for
      radical therapy to investigate factors that could influence survival. Clinical,
      pathologic, and molecular data of patients were analyzed by univariate and
      multivariate analysis. The overall actuarial probability of survival at year 1,
      2, 3, 4, 5, and 6 was 72%, 41%, 38%, 24%, 20%, and 9%. At univariate analysis,
      alpha-fetoprotein (AFP) (P =.0082); alkaline phosphatase (P =.0281); bilirubin (P
      =.0076); etiology (P =.0001); increment of tumor mass at month 3 (P =.0051); type
      of estrogen receptor (ER) in the tumor (P =.0000); prothrombin time (P =.0003);
      and portal vein thrombosis (P =.0000) had prognostic significance. At
      multivariate analysis, only type of ER (P =.0000) and bilirubin (P =.0030) showed
      independent predictive value for mortality. Survival was significantly longer in
      patients with wild-type estrogen receptors (P =.0000). Cumulative probability of
      survival at year 1, 2, 3, 4, 5, and 6 was 94%, 66%, 52%, 43%, 35%, and 18% for
      wild-type and 51%, 21%, 16%, and 9% for variant estrogen receptors (no patients
      alive after 4 years). Hepatitis B surface antigen (HBsAg)-positive patients with
      variant ERs had a median survival of 8 months versus 45 months in anti-hepatitis
      C virus-positive patients with wild-type ERs (P =.0001). In conclusion, (1) the
      presence of variant liver ER transcripts in the tumor was the strongest negative
      predictor of survival in inoperable hepatocellular carcinoma; (2) their presence
      was associated with spontaneous survival significantly worse than in patients
      with wild-type estrogen receptors; and (3) HBsAg-positive patients with variant
      receptors were characterized by the worst survival.

PMID- 10915730
TI  - Selective loss of nucleoside carrier expression in rat hepatocarcinomas.
AB  - Evidence that hepatoma cell lines show differential expression of concentrative
      nucleoside transporters (CNT1 and CNT2) prompted us to study the transporter
      proteins in 2 models of hepatocarcinogenesis, the chemically induced Solt and
      Farber model and the albumin-SV40 large T antigen (Alb-SV40) transgenic rat. CNT1
      expression was lower in tumor biopsy specimens from Alb-SV40 rat livers than in
      normal tissue. Immunocytochemistry revealed that the CNT1 protein was indeed
      absent in the tumor lesions. CNT1 was also absent in a cell line, L25, derived
      from the Alb-SV40 transgenic rat liver tumors, whereas another cell line, L37,
      derived from the normal-appearing parenchyma, retained the expression of both
      carrier isoforms. The protein expression correlated with the nucleoside transport
      properties of these cell lines. Moreover, although CNT2 expression was highly
      dependent on the growth characteristics of the 2 cell lines, as was CNT1 (albeit
      to a lower extent) in L37 cells, it was not expressed in L25 cells at any stage
      of cell growth. In contrast to the transgenic model of hepatocarcinogenesis, in
      the chemically induced tumors the expression of CNT2 was lower, although still
      detectable. In summary, these data indicate that hepatocarcinogenesis leads to a
      selective loss or diminished expression of nucleoside carrier isoforms, a feature
      that may be relevant to our understanding of the molecular basis of the
      bioavailability of those drugs that are nucleoside derivatives and may be
      substrates of these carriers. The transport properties and isoform-expression
      profile of the L25 and L37 cell lines make them suitable hepatocyte culture
      models with which to study nucleoside transport processes and drug sensitivity.

PMID- 10915731
TI  - Inhibition of transforming growth factor beta prevents progression of liver
      fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated
      rats.
AB  - We investigated whether anti-transforming growth factor beta (TGF-beta) molecular
      intervention can halt the progression of liver fibrosis in rats. To block TGF
      beta action in a specific manner, we prepared an adenovirus expressing a
      truncated type II TGF-beta receptor (AdTbeta-TR), which specifically inhibits TGF
      beta signaling as a dominant-negative receptor. We also used an adenovirus
      expressing bacterial beta-galactosidase (AdLacZ) as a control adenovirus. Rats
      were treated with dimethylnitrosamine (DMN) for 3 weeks; then, AdTbeta-TR,
      AdLacZ, or saline was intravenously applied once, followed by an additional 3
      week DMN treatment. The ratio between the truncated receptor and the wild-type
      receptor at the mRNA level was 15 at 1 week and 10 at 3 weeks after gene
      transfer. Immunohistostaining analysis showed that the truncated receptor was
      expressed mainly in septal cells including hepatic stellate cells. Liver
      fibrosis, as assessed by histology, hydroxyproline content, and the serum level
      of hyaluronic acid, progressed during the additional 3-week DMN treatment.
      However, in rats infected with AdTbeta-TR, the fibrosis remained at the level
      seen in rats given DMN for only 3 weeks. All AdTbeta-TR-treated rats remained
      alive, whereas DMN-treated rats infused with either AdLacZ or saline died of
      liver dysfunction. In the livers of AdTbeta-TR-treated rats, electron microscopy
      showed: 1) less accumulation of extracellular matrix proteins in the Disse's
      spaces; 2) regenerated hepatocytes; and 3) fat droplet-rich "quiescent" hepatic
      stellate cells. Our results demonstrate that TGF-beta plays a critical role in
      the progression of liver fibrosis, and suggest that anti-TGF-beta intervention
      should be therapeutic in already-established fibrotic livers, not only by
      suppressing fibrosis, but by facilitating hepatocyte regeneration.

PMID- 10915732
TI  - Concanavalin A simultaneously primes liver hematopoietic and epithelial
      progenitor cells for parallel expansion during liver regeneration after partial
      hepatectomy in mice.
AB  - Liver hematopoietic progenitor cells (LHPC) and liver epithelial progenitor cells
      (LEPC) share a remarkable number of growth and differentiation-controlling
      receptor-ligand signaling systems. These likely account for the ability of the
      liver to support hematopoiesis in fetal life, and possibly for suggestions that
      LHPC can differentiate into hepatocytes. In these experiments, the kinetics and
      magnitude of LHPC and LEPC activation and expansion were studied by using a
      concanavalin A (Con A) liver injury model followed by partial hepatectomy (PH).
      Studies were performed in interleukin 6-deficient (IL-6(-/-)) mice and wild-type
      (IL-6(+/+)) controls, which show equal susceptibility to Con A- induced injury,
      because IL-6/gp130 signaling has been implicated in both LHPC and LEPC expansion.
      Con A pretreatment primed LHPC and LEPC for a rapid and parallel expansion after
      PH in IL-6(+/+) mice, which was significantly blunted and delayed in the IL-6(-/
      ) mice. Exogenous IL-6 given immediately before PH after Con A, augmented both
      LHPC and LEPC expansion in the IL-6(-/-) mice. Thus, the proinflammatory cytokine
      IL-6, commonly produced in liver injury and inflammatory disease, is an important
      growth factor involved in the expansion of LHPC and LEPC. This observation has
      implications for both hepatic carcinogenesis and transplantation.

PMID- 10915733
TI  - Proteome analysis of rat hepatic stellate cells.
AB  - Proteome analysis was performed on cellular and secreted proteins of normal
      (quiescent) and activated rat hepatic stellate cells. The stellate cells were
      activated either in vitro by cultivating quiescent stellate cells for 9 days or
      in vivo by injecting rats with carbon tetrachloride for 8 weeks. A total of 43
      proteins/polypeptides were identified, which altered their expression levels when
      the cells were activated in vivo and/or in vitro. Twenty-seven of them showed
      similar changes in vivo and in vitro, including up-regulated proteins such as
      calcyclin, calgizzarin, and galectin-1 as well as down-regulated proteins such as
      liver carboxylesterase 10 and serine protease inhibitor 3. Sixteen of them showed
      different expression levels between in vivo and in vitro activated stellate
      cells. These results were reproducibly obtained in 3 independent experiments. The
      up-regulation of calcyclin, calgizzarin, and galectin-1, as well as the down
      regulation of liver carboxylesterase 10 were directly confirmed in fibrotic liver
      tissues. Northern blots confirmed up-regulation of the messenger RNAs (mRNAs) of
      calcyclin, calgizzarin, and galectin-1 in activated stellate cells, indicating
      that these changes were controlled at the mRNA level. In addition a list
      compiling over 150 stellate cell proteins is presented. The data presented here
      thus provide a significant new protein-level insight into the activation of
      hepatic stellate cells, a key event in liver fibrogenesis.

PMID- 10915735
TI  - Cold-preservation-induced sensitivity of rat hepatocyte function to rewarming
      injury and its prevention by short-term reperfusion.
AB  - With increasing time of cold preservation, levels of high-energy nucleotides in
      the liver are reducing. The authors hypothesized that cold preservation
      sensitizes hepatocyte function to ischemic injury occurring during graft
      rewarming and that the injury can be prevented by short-term reperfusion. Rat
      livers were cold-preserved in University of Wisconsin solution for 0 to 18 hours
      and ischemically rewarmed for 0 to 45 minutes to simulate the implantation stage
      of transplantation. Hepatobiliary function was assessed using a blood-free
      perfusion model. In comparison with controls, neither 18-hour preservation nor 45
      minute ischemic rewarming significantly influenced hepatocyte function. Compared
      with livers subjected to 45-minute ischemic rewarming, livers subjected to 9-hour
      preservation and 45-minute rewarming, and livers subjected to 18-hour
      preservation and 45-minute rewarming exhibited, respectively: 3.8 and 24 times
      reduced bile production, 4.3- and 116-fold decreased taurocholate excretion, and
      3.1 and 42 times depressed bromosulfophthalein excretion. Thirty-minute
      oxygenated warm reperfusion after 9- and 18-hour preservation nearly completely
      blunted sensitization of hepatocyte function to rewarming ischemia. The authors
      found that short-term oxygenated reperfusion restored adenine nucleotides in
      liver tissue to the values found before organ preservation and that reperfusion
      with energy substrate containing solutions increased tissue adenosine
      triphosphate concentration to a higher level than that found before preservation.
      In conclusion, sensitization of hepatocyte function to rewarming ischemia
      increases disproportionally with storage time, suggesting that this phenomenon
      may play a role in graft dysfunctions with increasing liver preservation time.
      Short-term oxygenated reperfusion of the liver may protect hepatocyte functions
      against warm ischemic insult, even after extended preservation.

PMID- 10915734
TI  - Alcoholic fatty liver differentially induces a neutrophil-chemokine and hepatic
      necrosis after ischemia-reperfusion in rat.
AB  - Primary graft nonfunction of steatotic liver allograft is one of the factors
      causing shortage of donor livers. Ischemia/reperfusion (I/R) injury is an
      important contributory factor to primary graft nonfunction. In this study, we
      investigated the complex chain of events from transcription factor activation to
      necrosis through cytokine induction and apoptosis in steatotic rat liver after
      warm I/R. Rats with alcoholic or nonalcoholic fatty liver were subjected to
      hepatic warm I/R and compared with control rats. Rats fed an ethanol diet for 6
      to 8 weeks developed severe hepatic necrosis accompanied by increased neutrophil
      recruitment after I/R, compared with rats with nonalcoholic fatty liver or
      control. Hepatic apoptosis as assessed by DNA fragmentation at 4 hours after I/R,
      however, increased to a similar degree in each of the 2 fatty liver models
      compared with the control. Alcoholic fatty liver exposed to I/R showed a rapid
      increase in nuclear factor-kappaB (NF-kappaB) binding activity at 1 hour after
      I/R, which preceded an increased expression of tumor necrosis factor alpha (TNF
      alpha) and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In contrast,
      nonalcoholic fatty liver did not show such potentiation of either NF-kappaB
      activation or cytokine induction after I/R. Our results have indicated that
      alcoholic fatty liver may differentially induce CINC-1 production and hepatic
      necrosis after I/R. Furthermore, our results suggest that apoptosis per se does
      not always lead to necrosis in the liver following I/R.

PMID- 10915736
TI  - Contribution of adenosine A(2) receptors and cyclic adenosine monophosphate to
      protective ischemic preconditioning of sinusoidal endothelial cells against
      Storage/Reperfusion injury in rat livers.
AB  - A brief period of liver ischemia decreases sinusoidal endothelial cell killing
      after cold liver storage and improves graft survival after liver transplantation,
      a phenomenon called ischemic preconditioning. In this study, we investigated the
      mechanism of sinusoidal endothelial cell protection after ischemic
      preconditioning. Livers were preconditioned by 5 minutes of ischemia and 5
      minutes of reperfusion. Subsequently, livers were stored for 30 hours in cold
      University of Wisconsin (UW) solution and reperfused briefly with physiological
      buffer containing Trypan blue. Ischemic preconditioning decreased sinusoidal
      endothelial cell killing after storage/reperfusion, as assessed by Trypan blue
      staining of nonparenchymal cells. Adenosine A(2) receptor blockade prevented the
      protective effect of ischemic preconditioning. By contrast, adenosine A(1)
      receptor blockade did not prevent protective ischemic preconditioning. Other rat
      livers were treated with adenosine A(1) and A(2) receptor agonists or dibutyryl
      cyclic adenosine monophosphate (DB-cAMP) before storage. The adenosine A(2)
      receptor agonist, CGS-21680, and DB-cAMP decreased sinusoidal endothelial cell
      killing to the same extent as ischemic preconditioning, but the adenosine A(1)
      receptor agonist, 2-chloro-N(6)-cyclopentyladenosine (CCPA), had no effect. The
      adenosine A(2) agonist and prostaglandin E(2), another agent that preconditions
      sinusoidal endothelial cells against storage/reperfusion injury, but not the
      adenosine A(1) agonist, increased cAMP levels in cultured sinusoidal endothelial
      cells. In conclusion, an adenosine A(2) receptor pathway coupled to increased
      cAMP mediates sinusoidal endothelial cell protection by ischemic preconditioning.

PMID- 10915737
TI  - Cytochrome P450-generated reactive metabolites cause mitochondrial permeability
      transition, caspase activation, and apoptosis in rat hepatocytes.
AB  - Although cytochrome P-450 (CYP)-generated reactive metabolites can cause
      hepatocyte apoptosis, the mechanism of this effect is incompletely understood. In
      the present study, we assessed the hepatotoxicity of skullcap, a diterpenoid
      containing herbal remedy. Male rat hepatocytes were incubated for 2 hours with
      skullcap diterpenoids (100 microg/mL). This treatment decreased cell glutathione
      and protein thiols and increased cell [Ca(2+)]. This activated Ca(2+)-dependent
      tissue transglutaminase, forming a cross-linked protein scaffold, and also opened
      the mitochondrial permeability transition pore, causing outer mitochondrial
      membrane rupture, increased cytosolic cytochrome c, activation of procaspase 3,
      internucleosomal DNA fragmentation, and ultrastructural features of apoptosis.
      Cell death was increased by a CYP3A inducer (dexamethasone) or a sulfur amino
      acid-deficient diet increasing glutathione depletion. In contrast, cell death was
      prevented by decreasing CYP3A activity (with troleandomycin), preventing
      glutathione depletion (with cysteine or cystine), blocking Ca(2+)-modulated
      events (with calmidazolium), preventing mitochondrial permeability transition
      (with cyclosporin A), or inhibiting caspase 3 (with acetyl-Asp-G u-Va-Asp-a
      dehyde). Both calmidazolium and cyclosporin A also prevented the increase in
      cytosolic cytochrome c and procaspase 3 activation. In conclusion, CYP3A
      activates skullcap diterpenoids into reactive metabolites that deplete cellular
      thiols and increase cell [Ca(2+)]. This activates Ca(2+)-dependent
      transglutaminase and also opens the mitochondrial permeability transition pore,
      causing outer mitochondrial membrane rupture, cytochrome c release, and caspase
      activation. Preventing mitochondrial permeability transition pore opening and/or
      caspase activity blocks apoptosis, showing the fundamental role of these final
      events in metabolite-mediated hepatotoxicity.

PMID- 10915738
TI  - Bax-mediated apoptosis in the livers of rats after partial hepatectomy in the
      retrorsine model of hepatocellular injury.
AB  - Retrorsine is a member of the pyrrolizidine alkaloid family of compounds whose
      toxic effects on the liver include a long-lasting inhibition of the proliferative
      capacity of hepatocytes. Despite the retrorsine-induced blockade of hepatocyte
      proliferation, retrorsine-exposed rats are able to reconstitute completely their
      liver mass after surgical partial hepatectomy (PH) via the sustained
      proliferation of a population of small, incompletely differentiated hepatocyte
      like progenitor cells (SHPCs). The extensive proliferation of SHPCs in retrorsine
      injured livers is accompanied by the progressive loss of irreversibly injured
      megalocytes. To study the mechanism by which retrorsine-damaged hepatocytes are
      removed after PH, we performed TUNEL analysis to establish apoptotic indices for
      hepatocytes in the livers of retrorsine-exposed and control rats up to 14 days
      post-PH. Apoptotic indices are highest (approximately 6.0%) in the livers of
      retrorsine-exposed rats at 1 day post-PH, gradually declining thereafter, yet
      remaining significantly elevated (approximately 1%) over control rats (<0.1%) at
      14 days post-PH (P <.05). After PH, levels of the proapoptotic protein Bax are
      increased in livers from retrorsine-exposed rats relative to the levels observed
      in control livers. Similarly, levels of the antiapoptotic protein Bcl-x(L) are
      significantly decreased (P <.05) compared with controls at t = 0 resulting in an
      increased (approximately 3.5-fold) Bax/Bcl-x protein ratio that is significantly
      elevated (P <.05) compared with controls. Finally, increased levels of Bax
      protein are localized to the mitochondria of retrorsine-exposed rat livers after
      PH during the same time that cytochrome c is released. These observations combine
      to suggest that retrorsine-injured hepatocytes are removed after PH via apoptotic
      pathways dependent on relative levels and localization of Bax and Bcl-x(L)
      protein.

PMID- 10915739
TI  - Hepatocellular response to chemical stress in CD-1 mice: induction of early genes
      and gamma-glutamylcysteine synthetase.
AB  - Exposure of cells to toxic chemical species can result in reduced glutathione
      (GSH) depletion, generation of free radicals, and/or binding to critical cell
      determinants. Chemical stress is usually followed by a concerted cellular
      response aimed at restoring homeostasis, although the precise initial stimulus
      for the response is unclear. We have focused on one component of this stress
      response, the up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS) and
      the preceding molecular events involved in its regulation in an in vivo mouse
      model. Male CD-1 mice received buthionine sulphoximine (BSO; 7.2 mmol/kg),
      diethyl maleate (DEM; 4.2 mmol/kg), paracetamol (APAP; 3.5 and 1.0 mmol/kg), or
      carbon tetrachloride (CCl(4); 1.0 and 0.2 mmol/kg). Biochemical (serum
      transaminase and hepatic GSH levels) and molecular (c-jun and c-fos messenger RNA
      [mRNA] levels and activator protein 1 [AP-1] DNA binding activity) parameters
      were measured, as well as the consequent effects on gamma-GCS levels and
      activity. All compounds produced GSH depletion, but only the higher doses of APAP
      and CCl(4) caused liver damage. DEM, APAP, and CCl(4) increased c-jun and c-fos
      mRNA levels, together with an increase in AP-1 binding; BSO failed to induce AP-1
      despite an increase in c-fos. Interestingly, the effects on gamma-GCS varied
      markedly according to the compound: BSO and DEM increased gamma-GCS enzyme
      activity, although only DEM, but not BSO, resulted in an increase in gamma-GCS(h)
      mRNA and protein. In contrast, APAP and CCl(4) both increased gamma-GCS(h) mRNA
      and protein; however, there was a marked dose-dependent decrease in gamma-GCS
      activity. These data indicate that the effect of chemical stress on the liver is
      compound specific and is not merely dependent on depletion of GSH.

PMID- 10915740
TI  - Expression of cystic fibrosis transmembrane conductance regulator in liver tissue
      from patients with cystic fibrosis.
AB  - The authors examined the expression of cystic fibrosis transmembrane conductance
      regulator (CFTR) and its relationship to histopathological changes in cystic
      fibrosis (CF) liver tissue. Immunohistochemistry was used to examine expression
      of CFTR, intercellular adhesion molecule-1 (ICAM-1) and liver cell-type markers
      in liver cryosections in 11 patients with CF-associated liver disease, and non-CF
      controls with (n = 17) and without (n = 3) liver disease. In CF patients
      prominent inflammatory infiltrates were not found, yet hepatic stellate cells
      were identified within fibrotic areas around bile ducts. Proliferating bile ducts
      displayed ICAM-1 immunoreactivity in 3 cases, but bile ducts were otherwise
      negative. In 2 patients homozygous for R764X and for 1112delT no CFTR
      immunoreactivity was detected. Bile-duct epithelial cells in patients carrying
      the DeltaF508 mutation displayed aberrant cytoplasmic immunolocalization of CFTR,
      as determined with confocal laser scanning microscopy, in contrast to the
      distinct CFTR expression at the luminal surface seen in controls. No clear
      relationship between CFTR expression and fibrosis or inflammation was evidenced
      in CF patients. In conclusion, these findings are consistent with an impairment
      of DeltaF508 CFTR processing in intrahepatic biliary epithelium. ICAM-1
      expression on bile-duct epithelial cells and inflammatory infiltrates were rare
      findings in CF liver tissue, indicating that immunological mechanisms are
      unlikely to be involved in initiation of CF-associated liver disease.

PMID- 10915741
TI  - Regulation of multidrug resistance 2 P-glycoprotein expression by bile salts in
      rats and in primary cultures of rat hepatocytes.
AB  - Biliary phospholipid secretion is tightly coupled to the secretion of free
      cholesterol and bile salts. The secretion of phospholipids across the canalicular
      membrane of hepatocytes occurs via the multidrug resistance 2 (mdr2) P
      glycoprotein (Pgp). The mechanism underlying the coupling of bile salt and
      phospholipid secretion has not been elucidated. The aims of this study were to
      determine the effects of bile acid structure on the expression of mdr2 in vitro
      and in vivo. Under optimal culture conditions, taurine-conjugated bile acids (50
      micromol/L) increased mdr2 messenger RNA (mRNA) levels in the following order:
      taurocholate (TCA) (288 +/- 36%, P <. 005) = taurodeoxycholate (TDCA) (276 +/-
      36%, P <.025) > taurochenodeoxycholate (TCDCA) (216 +/- 34%, P <.025) >
      tauroursodeoxycholate (TUDCA) (175 +/- 28%, P <.05) of control levels. The
      increase in mdr2 mRNA levels by TCA was both time and concentration dependent.
      Cholate feeding to rats with intact enterohepatic circulation increased mdr2
      transcriptional activity by 4-fold and protein mass by 1.9-fold. Chronic biliary
      diversion (CBD) decreased mdr2 mRNA levels to 66 +/- 9% (P <.025) of sham
      operated controls. Intraduodenal infusion of TCA for 48 hours in CBD rats caused
      a significant increase in mdr2 mRNA levels (224%) as compared with CBD controls.
      A diet high in cholesterol (4%) decreased mdr2 mRNA levels to 57% +/- 2 (P <.001)
      of pair-fed controls. Squalestatin (1 micromol/L), an inhibitor of cholesterol
      biosynthesis, increased mdr2 mRNA levels by 8.8-fold (P <.005) in hepatocyte
      cultures after 24 hours. In conclusion, in the rat, bile acids up-regulated mdr2
      transcriptional activity whereas cholesterol decreased mdr2 mRNA both in vitro
      and in vivo.

PMID- 10915742
TI  - Rab3D, a small GTP-binding protein implicated in regulated secretion, is
      associated with the transcytotic pathway in rat hepatocytes.
AB  - Rab3 isotypes are expressed in regulated secretory cells. Here, we report that
      rab3D is also expressed in rat hepatocytes, classic models for constitutive
      secretion. Using reverse transcriptase polymerase chain reaction (RT-PCR) with
      primers specific for rat rab3D, we amplified a 151 base pair rab3D fragment from
      total RNA extracted from primary cultures of rat hepatocytes. Immunoblot analysis
      using polyclonal antibodies to peptides representing the N- and C-terminal
      hypervariable regions of murine rab3D recognized a protein of approximately 25 kd
      in hepatocyte lysates, hepatic subcellular fractions, and tissue extracts. The
      distribution of rab3D was primarily cytosolic; however, only membrane-associated
      rab3D significantly bound guanosine triphosphate (GTP) in overlay assays. Several
      lines of investigation indicate that rab3D is associated with the transcytotic
      pathway. First, rab3D was enriched in a crude vesicle carrier fraction (CVCF),
      which includes transcytotic carriers. Vesicular compartments immunoisolated from
      the CVCF on magnetic beads coated with anti-rab3D antibody were enriched in the
      transcytosed form of the polymeric IgA receptor (pIgA-R), but lacked not only the
      pIgA-R precursor form associated with the secretory pathway, but also a Golgi
      marker protein. Second, indirect immunofluorescence on frozen liver sections and
      in polarized cultured hepatocytes localized rab3D-positive sites at or near the
      apical plasma membrane and to the pericanalicular cytoplasm. Finally, cholestasis
      induced by bile duct ligation (BDL), a manipulation known to slow transcytosis,
      caused rab3D to accumulate in the pericanalicular cytoplasm of cholestatic
      hepatocytes. Our results indicate that rab3D plays a role in the regulation of
      apically directed transcytosis in rat hepatocytes.

PMID- 10915743
TI  - Human homologue of maid: A dominant inhibitory helix-loop-helix protein
      associated with liver-specific gene expression.
AB  - The helix-loop-helix (HLH) family of transcriptional regulatory proteins are key
      regulators in numerous developmental processes. The class I HLH proteins, such as
      E12 are ubiquitously expressed. Class II HLH proteins, such as MyoD, are
      expressed in a tissue-specific manner. Class I and II heterodimers can bind to E
      boxes (CANNTG) and regulate lineage commitments of embryonic cells. In an attempt
      to identify partners for the E12 protein that may exert control during liver
      development, we performed the yeast 2-hybrid screen using an expression
      complementary DNA library from human fetal liver. A novel dominant inhibitory HLH
      factor, designated HHM (human homologue of maid), was isolated and characterized.
      HHM is structurally related to the Id family and was highly expressed in brain,
      pituitary gland, lung, heart, placenta, fetal liver, and bone marrow. HHM
      physically interacted with E12 in vitro and in mammalian cells. Comparison of the
      dominant inhibitory effects of HHM and Id2 on the binding of E12/MyoD dimer to an
      E-box element revealed a weaker inhibition by HHM. However, HHM but not Id2
      specifically inhibited the luciferase gene activation induced by hepatic nuclear
      factor 4 (HNF4) promoter. The HHM was transiently expressed during stem-cell
      driven regeneration of the liver at the stage in which the early basophilic foci
      of hepatocytes started to appear. These results suggest that HHM is a novel type
      of dominant inhibitory HLH protein that might modulate liver-specific gene
      expression.

PMID- 10915744
TI  - Effects of carcinogen-induced transcription factors on the activation of
      hepatitis B virus expression in human hepatoblastoma HepG2 cells and its
      implication on hepatocellular carcinomas.
AB  - To elucidate the molecular mechanisms involved in the action of common
      carcinogens, which can act as important cofactors in modulating hepatitis B virus
      mediated hepatocellular carcinogenesis, we have investigated the influence of
      aflatoxin B(1) (AFB), a potent liver carcinogen, as well as benzo[a]pyrene (BP)
      and 4-aminobiphenyl (4-ABP), carcinogens in cigarette smoke, on the induction of
      various transcription factors in human hepatoblastoma HepG2 cells. DNA
      electrophoretic mobility shift assays were performed with nuclear extracts from
      HepG2 cells treated with 10 micromol/L AFB, 40 micromol/L BP, or 300 micromol/L 4
      ABP for 6 and 24 hours. Eight- and 6-fold increases in nuclear transcription
      factor kappaB (NF-kappaB), and 5- and 10-fold increases in activated protein (AP
      1) transcription factor were observed with 24 hours AFB and BP treatments,
      respectively, whereas 4-ABP treatment resulted in an approximately 4-fold
      induction of both NF-kappaB and AP-1. Moreover, 4-ABP gave the strongest NF
      kappaB activation in 6 hours of treatment. Four- and 10-fold activation of stress
      protein was detected by a consensus heat shock factor (HSF) sequence binding
      probe, with AFB and BP treatments, respectively. DNA adducts were observed by
      immunoassays in HepG2 cells treated with AFB and BP but not with 4-ABP. Increased
      human hepatitis B virus (HBV) surface antigen (HBsAg) synthesis was detected in
      AFB- and BP-treated HepG2 cells following transfection with recircularized HBV
      DNA. These data suggest that certain carcinogen-induced transcription factors may
      influence viral carcinogenesis and initiate hepatocellular carcinomas (HCC).

PMID- 10915745
TI  - Pretransplantation hepatitis C virus quasispecies may be predictive of outcome
      after liver transplantation.
AB  - The evolution of hepatitis C virus (HCV) envelope variation was studied using a
      liver-transplant model to evaluate the role of HCV quasispecies for hepatocyte
      infection. Twelve HCV polymerase chain reaction (PCR)-positive liver-transplant
      recipients (6 with posttransplantation biochemical hepatitis and 6 without
      hepatitis [controls]) were prospectively evaluated and underwent detailed
      quasispecies analysis of pre- and postoperative serum samples. HCV amino acid
      sequence diversity and complexity at the first hypervariable region (HVR1) of the
      second envelope protein (E2) was correlated with outcome. Recurrence of HCV
      induced allograft injury was defined by persistently elevated serum alanine
      transaminase (ALT) levels. The major variant (sequences >10% of all clones) of
      recipients with hepatitis accounted for a significantly smaller percent of all
      preoperative clones compared with controls (41% +/- 6% vs. 69% +/- 8%; P <.015).
      Recipients with hepatitis had an increased number of pretransplantation major
      variants (2.5 +/- 0.3 vs. 1.1 +/- 0.2; P <.006). Eighty-three percent of controls
      had a predominant variant (accounting for >50% of clones) compared with 17% of
      those with recurrence (P <.05). These differences did not persist
      postoperatively. In addition, recipients without a pretransplantation predominant
      variant demonstrated an increased allograft fibrosis score (2.3 +/- 0.3 vs. 0.5
      +/- 0.3; P <.015) at 181 to 360 days posttransplantation compared with those in
      whom a predominant variant was present. Increased HCV envelope complexity may act
      as a stronger antigenic stimulus or improve hepatocyte receptor binding and lead
      to allograft hepatitis and fibrosis. Although pretransplantation differences in
      HCV quasispecies did not persist postoperatively, pretransplantation quasispecies
      may be a predictor of HCV-induced hepatitis and graft fibrosis after liver
      transplantation.

PMID- 10915746
TI  - Specific detection of minus-strand hepatitis C virus RNA by reverse-transcription
      polymerase chain reaction on PolyA(+)-purified RNA.
AB  - A full-length complementary DNA (cDNA) clone of the hepatitis C virus (HCV)
      genome was used to prepare full-length plus- and minus-strand RNA. The minus
      strand RNA, which contains a polyA(+) tract complementary to the polyU tract
      found in the plus strand (genomic) RNA, but not the plus strand RNA, was captured
      with a commercial polyA(+)-tract isolation system. After elution, the minus
      strand was amplified by reverse-transcription polymerase chain reaction (RT-PCR).
      The combination of this procedure and RT-PCR using rTth resulted in an
      unprecedented level of discrimination of 10 logs(10). HCV minus-strand RNA
      isolation was unaffected by the addition of an excess of 10(4) of plus strands or
      by the addition of cellular RNA, and although the polyA(+) isolation step removed
      99. 99% of plus strands, there was no loss of minus-strand signal. Minus-strand
      RNA was detected in RNA extracted from 4/4 liver samples and 4/8 peripheral blood
      mononuclear cells (PBMC) samples examined. Because the titer of plus-strand HCV
      RNA in any sample makes a significant contribution to false, random, and self
      priming, removal of the plus strand in this manner results in the most accurate
      method yet devised to confirm the replication of HCV in a population of cells.

PMID- 10915747
TI  - Evaluation of a new enzyme immunoassay for hepatitis C virus (HCV) core antigen
      with clinical sensitivity approximating that of genomic amplification of HCV RNA.
AB  - The aim of this study was to analyze the clinical performance of a new enzyme
      immunoassay (EIA) for hepatitis C virus (HCV) core antigen in comparison with the
      reverse transcription polymerase chain reaction (RT-PCR). A total of 310 patients
      with acute or chronic hepatitis C, and 132 HCV-negative controls were studied.
      Chemiluminescence EIA with monoclonal anti-HCV core antigen was used, and
      qualitative and quantitative commercial RT-PCRs and an in-house nested RT-PCR
      were performed. Compared with nested RT-PCR, the core antigen assay showed 97%
      sensitivity and 100% specificity in 75 patients with chronic hepatitis C and 132
      controls. HCV core antigen was positive in 16 (94%) of 17 patients with acute
      hepatitis C at initial consultation. In 3 persons prospectively followed, core
      antigen was detected in the first available (1-3 weeks) post-transfusion sample.
      In 167 anti-HCV-positive individuals, 129 (77%) were viremic; core antigen was
      detected in 126 (98%) compared with 129 (100%) for nested RT-PCR and 121 (94%)
      for the commercial RT-PCR. In 48 patients with chronic hepatitis C treated with
      interferon alfa, the concentration of core antigen before treatment was
      significantly (P <.002) lower in patients with sustained response than in
      nonresponders. All responders had a sustained loss of core antigen, whereas all
      nonresponders remained core antigen positive. The concentrations of HCV core
      antigen and HCV RNA correlated significantly (n = 48, r =.627, P <.001). In
      conclusion, the HCV core antigen assay is useful for the diagnosis of acute and
      chronic hepatitis C, and for predicting and monitoring the effect of interferon
      alfa treatment.

PMID- 10915748
TI  - Combination therapy with lamivudine and famciclovir for chronic hepatitis B
      infected Chinese patients: a viral dynamics study.
AB  - In vitro studies have shown that lamivudine and penciclovir (the active
      metabolite of famciclovir) act synergistically to inhibit hepatitis B virus (HBV)
      replication. We compared the effectiveness of HBV viral suppression by lamivudine
      monotherapy versus lamivudine plus famciclovir combination therapy in Chinese
      patients with chronic HBV infection. Twenty-one Chinese hepatitis B e antigen
      (HBeAg)-positive patients, with detectable HBV DNA (Digene Hybrid Capture II),
      were randomized to receive either lamivudine 150 mg/d orally (group 1, 9
      patients) or lamivudine 150 mg/d plus famciclovir 500 mg 3 times a day orally
      (group 2, 12 patients) for 12 weeks, with a follow-up period of at least 16
      weeks. Serial serum HBV-DNA levels were determined and a mathematical model with
      provision for incomplete inhibition of virus production during therapy was
      applied to analyze the dynamics of viral clearance. The mean antiviral efficacy
      was significantly greater in group 2 than in group 1 (0.988 +/- 0.012 vs. 0.94 +/
      0.03, P =.0012). HBV DNA returned to pretreatment level within 16 weeks after
      the end of initial treatment in 4 patients (66.7%) in group 1 and none in group 2
      (P =.08), who remained HBeAg positive and received no further treatment after
      week 12. Hence, in Chinese chronic HBeAg-positive patients, combination therapy
      using lamivudine and famciclovir was superior to lamivudine monotherapy in
      inhibiting HBV replication. Further studies of longer duration are needed to
      define whether combination therapy will increase the HBeAg seroconversion rate
      and decrease the rate of emergence of lamivudine-resistant variants.

PMID- 10915749
TI  - The significance of baseline serum alanine aminotransferase on pretreatment
      disease characteristics and response to antiviral therapy in chronic hepatitis C.
AB  - We sought to determine whether pretreatment serum alanine aminotransferase (ALT)
      levels in patients with chronic hepatitis C virus (HCV) correlate with
      demographic features and other disease characteristics and whether these values
      influence response to therapy. A total of 1,744 patients with HCV received either
      interferon alfa-2b and placebo or combination interferon alfa-2b and ribavirin
      for 24 or 48 weeks. Of these, 105 individuals (6%) had minimally raised serum ALT
      determinations at entry visit of </=1.3 x the upper limit of normal (ULN). By
      analysis of variance both pretreatment histologic activity index (HAI) scores (P
      <.0001) and fibrosis scores (P =.003) were significantly lower among patients
      with baseline ALT levels </=1.3 x ULN. Individuals with lower pretreatment ALT
      values were younger and weighed less than the ALT >1.3 x ULN cohort. Baseline ALT
      was not related to gender, race, baseline viral level, or HCV genotype. Using
      logistic regression analysis, the only demographic feature associated with ALT
      </=1.3 x ULN was lower baseline weight and lower baseline HAI score. There was no
      difference in sustained response between patients with baseline ALT levels </=1.3
      x ULN and those with >1.3 x ULN, in all treatment groups (26 of 105, 24.8% for
      ALT </=1.3 x ULN; 440 of 1, 639, 26.8% for ALT >1.3 x ULN). We conclude that HCV
      patients with minimally raised ALT values (</=1.3 x ULN) weigh less, and have
      lower histologic inflammatory scores than patients with more conventionally
      elevated ALT levels. Despite these differences, these patients have a similar
      sustained response to antiviral therapy.

PMID- 10915750
TI  - Activation of intracellular signaling by hepatitis B and C viruses: C-viral core
      is the most potent signal inducer.
AB  - To clarify the effects of hepatitis C virus (HCV) infection on hepatocytes, we
      analyzed and compared the induction of intracellular signals by HCV and hepatitis
      B virus (HBV) proteins. We examined the influence of 7 HCV (core, NS2, NS3, NS4A,
      NS4B, NS5A, and NS5B) and 4 HBV (precore, core, polymerase, and X) proteins on 5
      well-defined intracellular signaling pathways associated with cell proliferation,
      differentiation, and apoptosis by use of a reporter assay. Viral protein
      expression vectors were cotransfected into mammalian cells with reporter vectors
      having a luciferase gene driven by the following inducible cis-enhancer elements:
      the cyclic adenosine monophosphate response element, the serum response element
      (SRE), and the binding sites for nuclear factor kappaB (NF-kappaB), activator
      protein 1 (AP-1), and serum response factor (SRF). In addition, the activation of
      signals by HCV proteins was examined in a reporter plasmid having a natural
      interleukin-8 (IL-8) promoter upstream of a luciferase gene. Of 11 HCV and HBV
      proteins, HCV core had the strongest influence on intracellular signals,
      especially NF-kappaB-, AP-1-, and SRE-associated pathways. HCV core's activation
      level exceeded that of HBV X protein, a well-characterized transactivator of
      these signals. Moreover, HCV core activated the IL-8 promoter through NF-kappaB
      and AP-1. For the other proteins, HCV NS4B showed signal activation, but signals
      were activated at a lesser extent. The luciferase reporter assay, a recently
      introduced technique, helped in the elucidation of molecular events underlying
      the inflammatory and proliferation process in the liver induced by HCV.

PMID- 10915751
TI  - A randomized, placebo-controlled study to evaluate the efficacy of 12-month
      famciclovir treatment in patients with chronic hepatitis B e antigen-positive
      hepatitis B.
AB  - We conducted a randomized, placebo-controlled clinical study evaluating
      famciclovir (500 mg 3 times daily and 1.5 g once daily) for 1 year (6 months post
      treatment follow-up) in patients with chronic hepatitis B e antigen (HBeAg)
      positive hepatitis B virus (HBV) infection. The study was conducted in 80 centers
      in North America, Europe, and Australia/New Zealand. A total of 417 patients with
      histologically documented chronic hepatitis B (histologic activity index [HAI]
      9.5-11.0) received famciclovir (500 mg 3 times daily or 1.5 g once daily) or
      placebo. Famciclovir 500 mg 3 times daily significantly reduced HBV DNA and
      median HAI scores versus placebo. By week 8, median HBV DNA decreased from 1,645
      to 283 MEq/mL (famciclovir 500 mg 3 times daily) and from 1,147 to 304 MEq/mL
      (famciclovir 1.5 g once daily), while increasing for placebo (1,617 to 1,685
      MEq/mL). Median change in HBV DNA at the end of therapy was -76% (famciclovir 500
      mg 3 times daily; P <.01) and -60% (famciclovir 1.5 g once daily; P =.25) versus 
      37% for placebo. Median change in HAI was -1.5 points (famciclovir 500 mg 3 times
      daily; P =.02) and -1.0 point (famciclovir 1.5 g once daily; P =.35) and zero for
      placebo. Fifty percent of patients receiving famciclovir 500 mg 3 times daily (P
      =.07) and 43% receiving 1.5 g once daily (P =.41) experienced >/=2 points
      improvement in HAI versus 37% for placebo. Nine percent of patients treated with
      famciclovir 500 mg 3 times daily underwent anti-HBeAg seroconversion with
      undetectable HBV DNA at end of follow-up versus 3% in the placebo group (P =.05).
      Famciclovir was well tolerated; the incidence of post-treatment alanine
      transaminase (ALT) elevations was comparable with placebo. In conclusion,
      famciclovir 500 mg 3 times daily gave modest suppression of viral replication,
      but translated into significant histologic improvement in median HAI score at 1
      year.

PMID- 10915752
TI  - Hepatitis C-induced hepatic allograft injury is associated with a
      pretransplantation elevated viral replication rate.
AB  - Hepatitis C virus (HCV) allograft infection after liver transplantation follows a
      variable but accelerated course compared with the nontransplantation population.
      Predictors of outcome and mechanisms of reinfection remain elusive. The
      accelerated HCV-induced allograft injury associated with a 10- to 20-fold
      increase in serum viral quantity posttransplantation was hypothesized to be the
      result of elevated intrahepatic viral replication rates. Patients (N = 23) with
      HCV-induced end-stage liver disease who underwent liver transplantation between
      October 1995 and December 1998 were prospectively studied. HCV-induced allograft
      injury was defined by posttransplantation persistent biochemical hepatitis or
      allograft fibrosis not explained by other diagnoses. Liver biopsies (N = 92) were
      obtained by protocol and when clinically indicated. Negative-strand HCV RNA
      (putative intermediate for replication) was detected by a strand-specific reverse
      transcription polymerase chain reaction (RT-PCR) assay and semiquantatively
      compared with constitutively expressed 18S rRNA. Recipients with increased
      pretransplantation replication were at increased risk for the development of
      posttransplantation biochemical hepatitis (P =.03), an increased rate of
      allograft fibrosis (P =.006), and increased mortality rate (40.0% vs. 0.0%; P
      =.02). There was no correlation with quantities of genomic HCV RNA in the serum
      with relative intrahepatic viral replication either before or after liver
      transplantation. The relative rate of HCV replication within the allograft was
      not elevated in the posttransplantation period compared with that seen within the
      explanted liver. Accelerated allograft injury caused by HCV may be predicted by
      viral replication rates within the explanted liver. The stable intrahepatic
      replication rate after transplantation suggests that elevated serum viral loads
      are the result of decreased viral clearance, possibly secondary to
      immunosuppressive therapy.

PMID- 10915753
TI  - Hepatitis viruses and signal transduction: true to the core?

PMID- 10915754
TI  - Combination chemotherapy for hepatitis B virus: the final solution?

PMID- 10915755
TI  - Hepatitis C virus and the host: An imbalance induced by immunosuppression?

PMID- 10915756
TI  - Maintenance interferon for chronic hepatitis C: more issues than answers?

PMID- 10915757
TI  - Dying in Fas traffic.

PMID- 10915758
TI  - Reversibly immortalized human hepatocytes: an eternal fountain of liver support?

PMID- 10915759
TI  - The TSC1 gene product, hamartin, negatively regulates cell proliferation.
AB  - Tuberous sclerosis is an autosomal dominant hereditary disease caused by
      mutations in either the TSC1 or the TSC2 tumor suppressor gene. The TSC1 gene on
      chromosome 9q34 encodes a 130 kDa protein named hamartin, and the TSC2 gene on
      chromosome 16p13.3 codes for tuberin, a 200 kDa protein. Here we show that
      expression of hamartin, assayed by immunoblot analyses, is high in G(0)-arrested
      cells and hamartin is expressed throughout the entire ongoing cell cycle. An
      interaction of hamartin and tuberin can be detected in every phase of the cell
      cycle. Ectopic expression of high levels of hamartin attenuates cellular
      proliferation. We provide evidence that this effect could depend on a coiled-coil
      region earlier proposed to be involved in binding of hamartin to tuberin. Further
      investigations revealed that hamartin affects cell proliferation via deregulation
      of G(1) phase. Our data have a clear impact on understanding the role of hamartin
      during development of this disease.

PMID- 10915760
TI  - The motor and tail regions of myosin XV are critical for normal structure and
      function of auditory and vestibular hair cells.
AB  - Recessive mutations in myosin 15, a class XV unconventional myosin, cause
      profound congenital deafness in humans and both deafness and vestibular
      dysfunction in mice homozygous for the shaker 2 and shaker 2(J) alleles. The
      shaker 2 allele is a previously described missense mutation of a highly conserved
      residue in the motor domain of myosin XV. The shaker 2(J) lesion, in contrast, is
      a 14.7 kb deletion that removes the last six exons from the 3"-terminus of the
      Myo15 transcript. These exons encode a FERM (F, ezrin, radixin and moesin) domain
      that may interact with integral membrane proteins. Despite the deletion of six
      exons, Myo15 mRNA transcripts and protein are present in the post-natal day 1
      shaker 2(J) inner ear, which suggests that the FERM domain is critical for the
      development of normal hearing and balance. Myo15 transcripts are first detectable
      at embryonic day 13.5 in wild-type mice. Myo15 transcripts in the mouse inner ear
      are restricted to the sensory epithelium of the developing cristae ampularis,
      macula utriculi and macula sacculi of the vestibular system as well as to the
      developing organ of Corti. Both the shaker 2 and shaker 2(J) alleles result in
      abnormally short hair cell stereocilia in the cochlear and vestibular systems.
      This suggests that Myo15 may be important for both the structure and function of
      these sensory epithelia.

PMID- 10915761
TI  - Expression pattern of the Nijmegen breakage syndrome gene, Nbs1, during murine
      development.
AB  - The Nijmegen breakage syndrome (NBS; MIM 251260), is an autosomal recessive
      disease characterized by microcephaly, growth retardation, immuno-deficiency and
      cancer predisposition. NBS cells show spontaneous chromosomal instability and
      hypersensitivity to ionizing radiation in combination with radioresistant DNA
      synthesis. At the cellular level, NBS has some features in common with ataxia
      teleangiectasia. In this study the murine Nbs1 gene was used for an expression
      study in mouse embryos at different developmental stages as well as in adult
      mice. A low level of expression is observed in all tissues. Highly specific
      expression was observed in organs with physiologic DNA double strand breakage
      (DSB), such as testis, thymus and spleen. Enhanced expression is also found at
      sites of high proliferative activity. These are the subventricular layer of the
      telencephalon and the diencephalon, the liver, lung, kidney and gut, as well as
      striated and smooth muscle cells in various organs. In the adult cerebellum the
      postmitotic Purkinje cells are marked specifically. These expression patterns
      suggest that in addition to the role of the Nbs1 gene product as part of a DNA
      DSB repair complex, the Nbs1 gene product may serve further functions during
      development.

PMID- 10915762
TI  - A cre-lox recombination system for the targeted integration of circular yeast
      artificial chromosomes into embryonic stem cells.
AB  - The ability to produce embryonic stem (ES) cell lines containing different yeast
      artificial chromosomes (YACs) integrated into the same location in the genome
      provides a system for comparing the bio-logical effects of YAC transgenes without
      the confounding influences of integration site and copy number. A targeting
      system was developed for the directed integration of circular YACs into mouse ES
      cells. The system combines Cre-lox recombination technology, specifically a
      positive-selection integration system, with circular YAC lipofection technology
      to achieve single copy targeted integration of a transgene. Three independent
      germline competent ES cell lines [lox-containing ES lines (designated LES)] were
      created that contain a '-neo-lox' cassette integrated at different sites within
      the ES genome. A plasmid containing YAC vector sequences and a complementary '
      neo-lox' cassette was used to circularize two linear YACs containing genomic DNA
      from human chromosome 21. The circularized YACs were then targeted to the lox
      sites of the LES cell lines. Polymerase chain reaction and Southern analysis
      demonstrated that 21% (5 of 24) of lox-recombinants contain a full-length intact
      YAC. This system will make the study of YAC transgenic mice more reliable and
      reproducible, allowing the potential for direct comparison of different
      transgenes expressed from the same site within the genome.

PMID- 10915763
TI  - CAG repeat length in RAI1 is associated with age at onset variability in
      spinocerebellar ataxia type 2 (SCA2).
AB  - Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant disorder caused by
      the expansion of a polymorphic (CAG)(n) tract, which is translated into an
      expanded polyglutamine tract in the ataxin-2 protein. Although repeat length and
      age at disease onset are inversely related, approximately 50% of the age at onset
      variance in SCA2 remains unexplained. Other familial factors have been proposed
      to account for at least part of this remaining variance in the polyglutamine dis
      orders. The ability of polyglutamine tracts to interact with each other, as well
      as the presence of intra-nuclear inclusions in other polyglutamine disorders, led
      us to hypothesize that other CAG-containing proteins may interact with expanded
      ataxin-2 and affect the rate of protein accumulation, and thus influence age at
      onset. To test this hypothesis, we used step-wise multiple linear regression to
      examine 10 CAG-containing genes for possible influences on SCA2 age at onset. One
      locus, RAI1, contributed an additional 4.1% of the variance in SCA2 age at onset
      after accounting for the effect of the SCA2 expanded repeat. This locus was
      further studied in SCA3/Machado-Joseph disease (MJD), but did not have an effect
      on SCA3/MJD age at onset. This result implicates RAI1 as a possible contributor
      to SCA2 neurodegeneration and raises the possibility that other CAG-containing
      proteins may play a role in the pathogenesis of other polyglutamine disorders.

PMID- 10915764
TI  - Fragile X CGG repeat structures among African-Americans: identification of a
      novel factor responsible for repeat instability.
AB  - The cryptic CGG repeat responsible for the fragile X syndrome, located in the 5'
      UTR of FMR1, is unique compared with the many other triplet repeat-causing
      diseases, making it ideal for identifying factors involved in repeat expansion
      that may be common to other triplet repeat diseases. To date, a number of factors
      have been identified which may influence repeat instability, including the number
      and position of interspersed AGGs, length of the 3' pure CGG repeat and haplotype
      background. However, nearly all such data were derived from studies of
      Caucasians. Using a large African-American population, we present the only
      comprehensive examination of factors associated with CGG repeat instability in a
      non-Caucasian population. Among Caucasians, susceptible alleles were thought to
      come from those in the intermediate repeat range (41-60 repeats); however, we
      find that susceptible alleles may come from a larger repeat pool (35-60 repeats)
      and are better defined by their pure CGG repeat and/or -presence of only one AGG
      interruption. These results demonstrate the existence of different susceptible
      alleles among world populations and may account for the similar prevalence of the
      fragile X syndrome in African-Americans compared with Caucasians despite the
      lower frequency of inter-mediate sized alleles in the African-American
      population. Finally, we show that repeat structures among unaffected African
      Americans with the most frequent fragile X haplotype background are either pure
      or contain a single distal interruption. We propose that the lack of a proximal
      most interruption is a novel factor involved in CGG repeat instability.

PMID- 10915765
TI  - Cellular and viral splicing factors can modify the splicing pattern of CFTR
      transcripts carrying splicing mutations.
AB  - Variable levels of aberrantly spliced cystic fibrosis transmembrane conductance
      regulator (CFTR ) transcripts were suggested to correlate with variable cystic
      fibrosis (CF) severity. We studied the effect of the cellular splicing factors,
      hnRNP A1 and ASF/SF2, and their adenoviral analogues, E4-ORF6 and E4-ORF3, that
      promote exon skipping and/or exon inclusion, on the splicing pattern of the CFTR
      mutation 3849+10kb C-->T and the 5T allele. These mutations can lead to cryptic
      exon inclusion and exon skipping, respectively. Overexpression of the cellular
      factors promoted exon skipping of pre-mRNA transcribed from minigenes carrying
      the mutation (p5T or p3849M). This led to a substantial decrease in the level of
      correctly spliced mRNA transcribed from p5T and generated correctly spliced mRNA
      transcribed from p3849M that was not found without overexpression of the factors.
      The viral factor, E4-ORF3, promoted exon inclusion and led to a substantial
      increase of the correctly spliced mRNA transcribed from the p5T. The factor, E4
      ORF6, activated exon skipping and generated correctly spliced mRNA transcribed
      from p3849M. Thus, overexpression of alternative splicing factors can modulate
      the splicing pattern of CFTR alleles carrying splicing mutations. These results
      are important for understanding the mechanism underlying phenotypic variability
      in CF and other genetic diseases.

PMID- 10915766
TI  - Link between a novel human gammaD-crystallin allele and a unique cataract
      phenotype explained by protein crystallography.
AB  - We describe a 5-year-old boy with a unique congenital cataract caused by
      deposition of numerous birefringent, pleiochroic and macroscopically prismatic
      crystals. Crystal analysis with subsequent automatic Edman degradation and matrix
      associated laser desorption ionization time-of-flight mass spectrometry have
      identified the crystal-forming protein as gammaD-crystallin (CRYGD) lacking the N
      terminal methionine. Sequencing of the CRYGD gene has shown a heterozygous C-->A
      transversion in position 109 of the inferred cDNA (36R-->S transversion of the
      processed, N-terminal methionine-lacking CRYGD). The lens protein crystals were X
      ray diffracting, and our crystal structure solution at 2.25 A suggests that
      mutant R36S CRYGD has an unaltered protein fold. In contrast, the observed
      crystal packing is possible only with the mutant protein molecules that lack the
      bulky Arg36 side chain. This is the first described case of human cataract caused
      by crystallization of a protein in the lens. It involves the third known mutation
      in the CRYGD gene but offers, for the first time, a causative explanation of the
      phenotype.

PMID- 10915767
TI  - A biochemical basis for the inherited susceptibility to aminoglycoside
      ototoxicity.
AB  - The A1555 G mutation in mitochondrial 12S rRNA has been found to be associated
      with non-syndromic deafness and aminoglycoside-induced deafness. The sensitivity
      to the aminoglycoside paromomycin has been analyzed in lymphoblastoid cell lines
      derived from five deaf individuals and five hearing individuals from an Arab
      Israeli family carrying the A1555G mutation, and three married-in controls from
      the same family. Exposure to a high concentration of paromomycin (2 mg/ml), which
      caused an 8% average increase in doubling time (DT) in the control cell lines,
      produced higher average DT increases (49 and 47%) in the A1555G mutation-carrying
      cell lines derived from symptomatic and asymptomatic individuals, respectively.
      The ratios of translation rates in the presence and absence of paromomycin, which
      reflected the effect of the drug on mitochondrial protein synthesis, were
      significantly decreased in the cell lines derived from symptomatic and
      asymptomatic individuals (by 30 and 28% on average, respectively), compared with
      the ratios in the control cell lines. These ratios showed, in both groups of
      mutant cell lines, a significant negative correlation with the ratios of DTs in
      the presence and absence of the antibiotic. These results have provided the first
      direct evidence that the mitochondrial 12S rRNA carrying the A1555G mutation is
      the main target of aminoglycosides. They suggest that these antibiotics exert
      their detrimental effect through an alteration of mitochondrial protein
      synthesis, which exacerbates the inherent defect caused by the mutation, reducing
      the overall translation rate down to and below the minimal level required for
      normal cellular function (40-50%).

PMID- 10915768
TI  - Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast
      DNA repair protein RAD23, HHR23A and HHR23B.
AB  - Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder
      caused by an expansion of the polyglutamine tract near the C-terminus of the MJD1
      gene product, ataxin-3. The mutant ataxin-3 forms intranuclear inclusions in
      cultured cells as well as in diseased human brain and also causes cell death in
      transfected cells. However, the normal function of ataxin-3 remains unknown. To
      explore the function of ataxin-3, we used the two-hybrid system to screen for the
      protein(s) that interacts with ataxin-3. We found that ataxin-3 interacts with
      two human homologs of the yeast DNA repair protein RAD23, HHR23A and HHR23B.
      Furthermore, we confirmed that ataxin-3 interacts with the -ubiquitin-like domain
      at the N-terminus of the HHR23 proteins, which is important for nucleotide
      excision repair; however, ataxin-3 does not interact with -ubiquitin, implying
      that ataxin-3 might be functionally associated with the HHR23 proteins through
      this specific interaction. The normal and mutant ataxin-3 proteins show no
      difference in their ability to bind to the HHR23 proteins. However, in 293 cells
      HHR23A is recruited to intranuclear inclusions formed by the mutant ataxin-3
      through its interaction with ataxin-3. These results suggest that this
      interaction is associated with the normal function of ataxin-3 and that some
      functional abnormality of the HHR23 proteins might exist in MJD.

PMID- 10915769
TI  - Mice with a targeted disruption of the Fanconi anemia homolog Fanca.
AB  - Fanconi anemia (FA) is a hereditary chromosomal instability syndrome with cancer
      predisposition. Bone marrow failure resulting in pancytopenia is the main cause
      of death of FA patients. Diagnosis of FA is based on their cellular
      hypersensitivity to DNA crosslinking agents and chromosome breakages. Somatic
      complementation experiments suggest the involvement of at least eight genes in
      FA. The gene for complementation group A (FANCA) is defective in the majority of
      FA patients. We show here that mice deficient of FANCA: are viable and have no
      detectable developmental abnormalities. The hematological parameters showed a
      slightly decreased platelet count and a slightly increased erythrocyte mean cell
      volume in mice at young age, but this did not progress to anemia. Consistent with
      the clinical phenotype of FA patients, both male and female mice showed
      hypogonadism and impaired fertility. Furthermore, embryonic fibroblasts of the
      knock-out mice exhibited spontaneous chromosomal instability and were hyper
      responsive to the clastogenic effect of the crosslinker mitomycin C.

PMID- 10915770
TI  - Expression and imprinting of MAGEL2 suggest a role in Prader-willi syndrome and
      the homologous murine imprinting phenotype.
AB  - Prader-Willi syndrome (PWS) is caused by the loss of expression of imprinted
      genes in chromosome 15q11-q13. Affected individuals exhibit neonatal hypotonia,
      developmental delay and childhood-onset obesity. Necdin, a protein implicated in
      the terminal differentiation of neurons, is the only PWS candidate gene to reduce
      viability when disrupted in a mouse model. In this study, we have characterized
      MAGEL2 (also known as NDNL1), a gene with 51% amino acid sequence similarity to
      necdin and located 41 kb distal to NDN in the PWS deletion region. MAGEL2 is
      expressed predominantly in brain, the primary tissue affected in PWS and in
      several fetal tissues as shown by northern blot analysis. MAGEL2 is imprinted
      with monoallelic expression in control brain, and paternal-only expression in the
      central nervous system as demonstrated by its lack of expression in brain from a
      PWS-affected individual. The orthologous mouse gene (Magel2) is located within
      150 kb of NDN:, is imprinted with paternal-only expression and is expressed
      predominantly in late developmental stages and adult brain as shown by northern
      blotting, RT-PCR and whole-mount RNA in situ hybridization. Magel2 distribution
      partially overlaps that of NDN:, with strong expression being detected in the
      central nervous system in mid-gestation mouse embryos by in situ hybridization.
      We hypothesize that, although loss of necdin expression may be important in the
      neonatal presentation of PWS, loss of MAGEL2 may be critical to abnormalities in
      brain development and dysmorphic features in individuals with PWS.

PMID- 10915771
TI  - A mouse model of galactose-induced cataracts.
AB  - Galactokinase (GK; EC 2.7.1.6) is the first enzyme in the metabolism of
      galactose. In humans, GK deficiency results in congenital cataracts due to an
      accumulation of galactitol within the lens. In an attempt to make a galactosemic
      animal model, we cloned the mouse GK gene (Glk1) and disrupted it by gene
      targeting. As expected, galactose was very poorly metabolized in GK-deficient
      mice. In addition, both galactose and galactitol accumulated in tissues of GK
      deficient mice. Surprisingly, the GK-deficient animals did not form cataracts
      even when fed a high galactose diet. However, the introduction of a human aldose
      reductase transgene into a GK-deficient background resulted in cataract formation
      within the first postnatal day. This mouse represents the first mouse model for
      congenital galactosemic cataract.

PMID- 10915772
TI  - Sequence conservation and variability of imprinting in the Beckwith-Wiedemann
      syndrome gene cluster in human and mouse.
AB  - In human and mouse most imprinted genes are arranged in chromosomal clusters.
      This linked organization suggests coordinated mechanisms controlling imprinted
      expression. We have sequenced 250 kb in the centre of the mouse imprinting
      cluster on distal chromosome 7 and compared it with the orthologous Beckwith
      Wiedemann gene cluster on human chromosome 11p15.5. This first comparative
      imprinting cluster analysis revealed a high structural and functional
      conservation of the six orthologous genes identified. However, several striking
      differences were also discovered. First, compared with the mouse the human
      sequence is approximately 40% longer, mostly due to insertions of two large
      repetitive clusters. One of these clusters encompasses an additional gene coding
      for a homologue of the ribosomal protein L26. Second, pronounced blocks of unique
      direct repeats characteristic of imprinted genes were only found in the human
      sequence. Third, two of the orthologous gene pairs Tssc4/TSSC4 and Ltrpc5/LTRPC5
      showed apparent differences in imprinting between human and mouse, whereas others
      like Tssc6/TSSC6 were not imprinted in either organism. Together these results
      suggest a significant functional and structural variability in the centre of the
      imprinting cluster. Some genes escape imprinting in both organisms whereas others
      exhibit tissue- and species-specific imprinting. Hence the control of imprinting
      in the cluster appears to be a highly dynamic process under fast evolutionary
      adaptation. Intriguingly, whereas imprinted genes within the cluster contain CpG
      islands the non-imprinted Ltrpc5 and Tssc6/TSSC6 do not. This and additional
      comparisons with other imprinted and non-imprinted regions suggest that CpG
      islands are key features of imprinted domains.

PMID- 10915773
TI  - Transplacental injection of somite-derived cells in mdx mouse embryos for the
      correction of dystrophin deficiency.
AB  - Duchenne muscular dystrophy (DMD) is a lethal recessive disease caused by the
      absence of dystrophin in skeletal muscle, heart and other tissues. No cure is
      available at present for DMD. Here we describe a new strategy for the correction
      of dystrophin deficiency based on the transplantation of normal somite-derived
      cells into mdx mouse embryos. Somite-derived cells were isolated from E11.5
      transgenic mouse embryos expressing the LacZ gene under the control of the muscle
      specific desmin promoter and injected into the uterine circulation of pregnant
      mdx mice at gestational days E11.5-E17. Approximately 30% of the injected mdx
      embryos survived the procedure. Donor somite-derived cells were able to cross the
      placenta and migrate into host embryonic tissues. The pattern of donor cell
      distribution in host tissues depended on the gestational age of the transplanted
      embryos. Cells were found in hindlimb muscles, diaphragm, heart and ribs in E11.5
      treated embryos and in the skull, ribs, vertebrae and lung of E15-E17 treated
      embryos. Normal dystrophin transcripts were detected in muscle and bone by RT
      PCR. Histochemical analysis showed co-localization of LacZ and dystrophin
      expression in 5% of soleus and quadriceps muscle fibres and in 4% of heart
      myocytes of two of seven 8-week-old treated mdx mice.

PMID- 10915774
TI  - Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene
      (Sim2) show phenotypes similar to some of those present in the partial trisomy 16
      mouse models of Down syndrome.
AB  - The Drosophila single-minded (sim) transcription factor, is a master regulator of
      fruitfly neurogenesis. Recently, we have cloned and mapped a human homolog of
      sim, SIM2, to chromosome 21 in the so-called 'Down syndrome chromosomal region'.
      Three copies of SIM2 may contribute to some Down syndrome (DS) phenotypes because
      of the mapping position function as transcriptional repressor, temporal and
      spatial expression pattern of mouse Sim2, and the potentially analogous role of
      human SIM2 to that of Drosophila sim during neurogenesis. In order to validate
      this hypothesis in vivo, we have created the first bacterial artificial
      chromosome transgenic mice overexpressing a gene possibly involved in DS with
      only one or two additional copies of mouse Sim2. The transgene was shown to be
      expressed in the same spatial pattern as the endogenous gene. The mice develop
      normally, are fertile and do not show detectable histopathological abnormalities.
      However, detailed analysis of their behavior revealed anxiety-related/reduced
      exploratory behaviour and sensitivity to pain, phenotypes similar to those also
      present in other partial trisomy 16 mouse models of DS. Our data therefore
      suggest that overexpression of SIM2 contributes to some of the complex DS
      phenotypes.

PMID- 10915775
TI  - Identification of two new Pmp22 mouse mutants using large-scale mutagenesis and a
      novel rapid mapping strategy.
AB  - Mouse mutants have a key role in discerning mammalian gene function and modelling
      human disease; however, at present mutants exist for only 1-2% of all mouse
      genes. In order to address this phenotype gap, we have embarked on a genome-wide,
      phenotype-driven, large-scale N-ethyl-N--nitrosourea (ENU) mutagenesis screen for
      dominant mutations of clinical and pharmacological interest in the mouse. Here we
      describe the identification of two similar neurological phenotypes and
      determination of the underlying mutations using a novel rapid mapping strategy
      incorporating speed back-crosses and high throughput genotyping. Two mutant mice
      were identified with marked resting tremor and further characterized using the
      SHIRPA behavioural and functional assessment protocol. Back-cross animals were
      generated using in vitro fertilization and genome scans performed utilizing DNA
      pools derived from multiple mutant mice. Both mutants were mapped to a region on
      chromosome 11 containing the peripheral myelin protein 22 gene (Pmp22). Sequence
      analysis revealed novel point mutations in Pmp22 in both lines. The first
      mutation, H12R, alters the same amino acid as in the severe human peripheral
      neuropathy Dejerine Sottas syndrome and Y153TER in the other mutant truncates the
      Pmp22 protein by seven amino acids. Histological analysis of both lines revealed
      hypo-myelination of peripheral nerves. This is the first report of the generation
      of a clinically relevant neurological mutant and its rapid genetic
      characterization from a large-scale mutagenesis screen for dominant phenotypes in
      the mouse, and validates the use of large-scale screens to generate desired
      clinical phenotypes in mice.

PMID- 10915776
TI  - Retinoschisin, the X-linked retinoschisis protein, is a secreted photoreceptor
      protein, and is expressed and released by Weri-Rb1 cells.
AB  - X-linked retinoschisis is characterized by microcystic-like changes of the
      macular region and schisis within the inner retinal layers, leading to visual
      deterioration in males. Many missense and protein-truncating mutations of the
      causative gene RS1 have now been identified and are thought to be inactivating.
      RS1 encodes a 224 amino acid protein, retinoschisin, which contains a discoidin
      domain but is of unknown function. We have generated a polyclonal antibody
      against a peptide from a unique region within retinoschisin, which detects a
      protein of approximately 28 kDa in retinal samples reduced with dithiothreitol,
      but multimers sized >40 kDa under non-reducing conditions. A screen of human
      tissues with this antibody reveals retinoschisin to be retina specific and the
      antibody detects a protein of similar size in bovine and murine retinae. We
      investigated the expression pattern in the retina of both RS1 mRNA (using in situ
      hybridization with riboprobes) and retinoschisin (using immunohistochemistry).
      The antisense riboprobe detected RS1 mRNA only in the photoreceptor layer but the
      protein product of the gene was present both in the photoreceptors and within the
      inner portions of the retina. Furthermore, differentiated retinoblastoma cells
      (Weri-Rb1 cells) were found to express RS1 mRNA and to release retinoschisin.
      These results suggest that retinoschisin is released by photo-receptors and has
      functions within the inner retinal layers. Thus, X-linked retinoschisis is caused
      by abnormalities in a putative secreted photoreceptor protein and is the first
      example of a secreted photo-receptor protein associated with a retinal dystrophy.

PMID- 10915777
TI  - Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot
      spot is not elevated above the genome average rate.
AB  - An increasing number of human diseases and syndromes are being found to result
      from micro-duplications or microdeletions arising from meiotic recombination
      between homologous repeats on the same chromosome. The first microduplication
      syndrome delineated, Charcot-Marie-Tooth disease type 1A (CMT1A), results from
      unequal crossing over between two >98% identical 24 kb repeats (CMT1A-REPs) on
      chromosome 17. In addition to its medical significance, the CMT1A region has
      features that make it a unique resource for detailed analysis of human unequal
      recombination. Previous studies of CMT1A patients showed that the majority of
      unequal crossovers occurred within a small region (<1 kb) of the REPs suggesting
      the presence of a recombination hot-spot. We directly measured the frequency of
      unequal recombination in the hot-spot region using sperm from four normal
      individuals. Surprisingly, unequal recombination between the REPs occurs at a
      rate no greater than the average rate for the male genome (approximately 1 cM/Mb)
      and is the same as that expected for equally aligned REPs. This conclusion
      extends to humans the findings in yeast that recombination between repeated
      sequences far apart on the same chromosome may occur at similar frequencies to
      allelic recombination. Finally, the CMT1A hot-spot stands in sharp contrast to
      the human MS32 mini-satellite-associated hot-spot that exhibits highly enhanced
      recombination initiation in addition to positional specificity. One possibility
      is that the CMT1A hot-spot may consist of a region with genome average
      recombination potential embedded within a recombination cold-spot.

PMID- 10915778
TI  - Human mini-chromosomes with minimal centromeres.
AB  - We have introduced a 6.5 Mb human mini-chromosome with a complex centromere
      structure into DT40 cells and have used sequence targeting and telomere-directed
      chromosome breakage to dissect the sequence requirements for centromere function.
      These experiments proved that a vertebrate centromere with two blocks of
      functional alphoid DNA separated by 2.5 Mb can exist as a stable structure in
      some but not all vertebrate cells. Further experiments indicated that recovery of
      chromosomes with less than approximately 100 kb of alphoid DNA is very
      inefficient, suggesting that a functional centromere requires a minimum of
      approximately 100 kb of alphoid DNA. Mini-chromosomes with minimal centromeres
      segregate accurately in some but not all vertebrate cells and should be useful
      for the detection of sequence-specific factors required for vertebrate centromere
      maintenance.

PMID- 10915779
TI  - Excitation-contraction coupling is not affected by scrambled sequence in residues
      681-690 of the dihydropyridine receptor II-III loop.
AB  - A peptide corresponding to residues 681-690 of the II-III loop of the skeletal
      muscle dihydropyridine receptor alpha(1) subunit (DHPR, alpha(1S)) has been
      reported to activate the skeletal muscle ryanodine receptor (RyR1) in vitro.
      Within this region of alpha(1S), a cluster of basic residues, Arg(681)-Lys(685),
      was previously reported to be indispensable for the activation of RyR1 in
      microsomal preparations and lipid bilayers. We have used an intact alpha(1S)
      subunit with scrambled sequence in this region of the II-III loop (alpha(1S)-scr)
      to test the importance of residues 681-690 and the basic motif for skeletal-type
      excitation-contraction (EC) coupling and retrograde signaling in vivo. When
      expressed in dysgenic myotubes (which lack endogenous alpha(1S)), alpha(1S)-scr
      restored calcium currents that were indistinguishable, in current density and
      voltage dependence, from those restored by wild-type alpha(1S). The scrambled
      DHPR also rescued skeletal-type EC coupling, as indicated by electrically evoked
      contractions in the presence of 0.5 mm Cd(2+) and 0.1 mm La(3+). Furthermore, the
      release of intracellular Ca(2+), as assayed by the indicator dye, Fluo-3, had
      similar kinetics and voltage dependence for alpha(1S) and alpha(1S)-scr. These
      data suggest that residues 681-690 of the alpha(1S) II-III loop are not essential
      in muscle cells for normal functioning of the DHPR, including skeletal-type EC
      coupling and retrograde signaling.

PMID- 10915781
TI  - Autocrine gastrins in colon cancer cells Up-regulate cytochrome c oxidase Vb and
      down-regulate efflux of cytochrome c and activation of caspase-3.
AB  - Suppression of the gastrin gene in human colon cancer cells by stably expressing
      antisense (AS) gastrin RNA results in significant growth suppression of AS cells.
      To understand mechanisms mediating the growth effects of autocrine gastrins,
      differential expression of transcripts by AS and control (C) clones of a
      representative cell line (HCT-116) was analyzed to identify target genes of
      autocrine gastrins. Six differentially expressed transcripts were confirmed and
      sequenced. Of these, the RNA and protein levels of cytochrome c oxidase (COX) Vb
      were significantly higher in C versus AS cells. The expression of COX Vb by colon
      cancer cells was proportional to the expression of gastrin. Higher levels of COX
      Vb coprecipitated with cytochrome c in the mitochondria of C versus AS cells.
      Treatment of mitochondria with digitonin resulted in a 2-fold higher release of
      cytochrome c from AS versus C mitochondria. As a corollary, the cytosolic levels
      of cytochrome c were significantly higher in AS versus C cells, which correlated
      with approximately 2- and approximately 3-fold higher activation of caspase-9 and
      -3, respectively, in AS versus C cells in response to camptothecin. Thus,
      autocrine gastrins may support growth/survival of cells by up-regulating COX Vb,
      which may decrease the sensitivity of the cancer cells to apoptotic stimuli by
      increasing retention of cytochrome c in mitochondria.

PMID- 10915780
TI  - The integrin-linked kinase regulates the cyclin D1 gene through glycogen synthase
      kinase 3beta and cAMP-responsive element-binding protein-dependent pathways.
AB  - The cyclin D1 gene encodes the regulatory subunit of a holoenzyme that
      phosphorylates and inactivates the pRB tumor suppressor protein. Cyclin D1 is
      overexpressed in 20-30% of human breast tumors and is induced both by oncogenes
      including those for Ras, Neu, and Src, and by the beta-catenin/lymphoid enhancer
      factor (LEF)/T cell factor (TCF) pathway. The ankyrin repeat containing serine
      threonine protein kinase, integrin-linked kinase (ILK), binds to the cytoplasmic
      domain of beta(1) and beta(3) integrin subunits and promotes anchorage
      independent growth. We show here that ILK overexpression elevates cyclin D1
      protein levels and directly induces the cyclin D1 gene in mammary epithelial
      cells. ILK activation of the cyclin D1 promoter was abolished by point mutation
      of a cAMP-responsive element-binding protein (CREB)/ATF-2 binding site at
      nucleotide -54 in the cyclin D1 promoter, and by overexpression of either
      glycogen synthase kinase-3beta (GSK-3beta) or dominant negative mutants of CREB
      or ATF-2. Inhibition of the PI 3-kinase and AKT/protein kinase B, but not of the
      p38, ERK, or JNK signaling pathways, reduced ILK induction of cyclin D1
      expression. ILK induced CREB transactivation and CREB binding to the cyclin D1
      promoter CRE. Wnt-1 overexpression in mammary epithelial cells induced cyclin D1
      mRNA and targeted overexpression of Wnt-1 in the mammary gland of transgenic mice
      increased both ILK activity and cyclin D1 levels. We conclude that the cyclin D1
      gene is regulated by the Wnt-1 and ILK signaling pathways and that ILK induction
      of cyclin D1 involves the CREB signaling pathway in mammary epithelial cells.

PMID- 10915782
TI  - Flavohemoglobin Hmp affords inducible protection for Escherichia coli
      respiration, catalyzed by cytochromes bo' or bd, from nitric oxide.
AB  - Respiration of Escherichia coli catalyzed either by cytochrome bo' or bd is
      sensitive to micromolar extracellular NO; extensive, transient inhibition of
      respiration increases as dissolved oxygen tension in the medium decreases. At low
      oxygen concentrations (25-33 microm), the duration of inhibition of respiration
      by 9 microm NO is increased by mutation of either oxidase. Respiration of an hmp
      mutant defective in flavohemoglobin (Hmp) synthesis is extremely NO-sensitive
      (I(50) about 0.8 microm); conversely, cells pre-grown with sodium nitroprusside
      or overexpressing plasmid-borne hmp(+) are insensitive to 60 microm NO and have
      elevated levels of immunologically detectable Hmp. Purified Hmp consumes O(2) at
      a rate that is instantaneously and extensively (>10-fold) stimulated by NO due to
      NO oxygenase activity but, in the absence of NO, Hmp does not contribute
      measurably to cell oxygen consumption. Cyanide binds to Hmp (K(d) 3 microm).
      Concentrations of KCN (100 microm) that do not significantly inhibit cell
      respiration markedly suppress the protection of respiration from NO afforded by
      Hmp and abolish NO oxygenase activity of purified Hmp. The results demonstrate
      the role of Hmp in protecting respiration from NO stress and are discussed in
      relation to the energy metabolism of E. coli in natural O(2)-depleted
      environments.

PMID- 10915783
TI  - Selective stimulation by ceramide of the expression of the alpha isoform of
      retinoic acid and retinoid X receptors in osteoblastic cells. A role of
      sphingosine 1-phosphate-mediated AP-1 in the ligand-dependent transcriptional
      activity of these receptors.
AB  - Recent studies have demonstrated that sphingosine 1-phosphate (SPP) plays a
      functional role as a signaling molecule in gene expression in several kinds of
      cells. The present study demonstrates selective expression by ceramide of
      retinoic acid receptor-alpha (RAR-alpha) and retinoic X receptor-alpha (RXR
      alpha) in osteoblastic MC3T3-E1 cells and a functional role of SPP-mediated AP-1
      in the signaling mechanism of ligand-dependent transcriptional activity of
      heterodimers of these receptors in the cells. C(2)- and C(6)-ceramides
      selectively stimulated the expression of RAR-alpha and RXR-alpha genes, but not
      that of beta and gamma isoform genes of RAR and RXR, in the cells. The C(2)
      ceramide-induced stimulation was clearly inhibited by dl-threo
      dihydrosphingosine, an inhibitor of sphingosine kinase. SPP also selectively
      stimulated the expression of both receptors and increased the specific binding of
      the nuclear proteins to direct repeat 5 (DR-5), a consensus sequence of RAR-RXR.
      In addition, SPP markedly stimulated transient chloramphenicol acetyltransferase
      (CAT) activity of retinoic acid-dependent transcriptional activity in the cells
      transfected with a DR-5-CAT reporter gene. The SPP stimulation was activation
      protein-1 (AP-1)-dependent, because the SPP stimulatory action toward these
      nuclear gene expressions and the transient CAT activity were inhibited by
      antisense c-fos and c-jun oligonucleotides. We observed that SPP actually
      stimulated AP-1 transcriptional activity in the cells. This study suggests an
      important role of SPP-mediated AP-1 in the selective expression of RAR-alpha and
      RXR-alpha in osteoblastic cells via the sphingosine pathway.

PMID- 10915784
TI  - Vacuolar H(+)-ATPase localized in plasma membranes of malaria parasite cells,
      Plasmodium falciparum, is involved in regional acidification of parasitized
      erythrocytes.
AB  - Recent biochemical studies involving 2',7'-bis-(2-carboxyethyl)-5, 6
      carboxylfluorescein (BCECF)-labeled saponin-permeabilized and parasitized
      erythrocytes indicated that malaria parasite cells maintain the resting
      cytoplasmic pH at about 7.3, and treatment with vacuolar proton-pump inhibitors
      reduces the resting pH to 6.7, suggesting proton extrusion from the parasite
      cells via vacuolar H(+)-ATPase (Saliba, K. J., and Kirk, K. (1999) J. Biol. Chem.
      274, 33213-33219). In the present study, we investigated the localization of
      vacuolar H(+)-ATPase in Plasmodium falciparum cells infecting erythrocytes.
      Antibodies against vacuolar H(+)-ATPase subunit A and B specifically
      immunostained the infecting parasite cells and recognized a single 67- and 55-kDa
      polypeptide, respectively. Immunoelectron microscopy indicated that the
      immunological counterpart of V-ATPase subunits A and B is localized at the plasma
      membrane, small clear vesicles, and food vacuoles, a lower extent being detected
      at the parasitophorus vacuolar membrane of the parasite cells. We measured the
      cytoplasmic pH of both infected erythrocytes and invading malaria parasite cells
      by microfluorimetry using BCECF fluorescence. It was found that a restricted area
      of the erythrocyte cytoplasm near a parasite cell is slightly acidic, being about
      pH 6.9. The pH increased to pH 7.3 upon the addition of either concanamycin B or
      bafilomycin A(1), specific inhibitors of vacuolar H(+)-ATPase. Simultaneously,
      the cytoplasmic pH of the infecting parasite cell decreased from pH 7.3 to 7.1.
      Neither vanadate at 0.5 mm, an inhibitor of P-type H(+)-ATPase, nor
      ethylisopropylamiloride at 0.2 mm, an inhibitor of Na(+)/H(+)-exchanger, affected
      the cytoplasmic pH of erythrocytes or infecting parasite cells. These results
      constitute direct evidence that plasma membrane vacuolar H(+)-ATPase is
      responsible for active extrusion of protons from the parasite cells.

PMID- 10915786
TI  - From malate dehydrogenase to phenyllactate dehydrogenase. Incorporation of
      unnatural amino acids to generate an improved enzyme-catalyzed activity.
AB  - Malate dehydrogenase (MDH) from Escherichia coli is highly specific for its keto
      acid substrate. The placement of the active site-binding groups in MDH
      effectively discriminates against both the shorter and the longer keto
      dicarboxylic acids that could potentially serve as alternative substrates. A
      notable exception to this specificity is the alternative substrate
      phenylpyruvate. This aromatic keto acid can be reduced by MDH, albeit at a
      somewhat slower rate and with greatly diminished affinity, despite the presence
      of several substrate-binding arginyl residues and the absence of a hydrophobic
      pocket in the active site. The specificity of MDH for phenylpyruvate has now been
      enhanced, and that for the physiological substrate oxaloacetate has been
      diminished, through the replacement of one of the binding arginyl residues with
      several unnatural alkyl and aryl amino acid analogs. This approach, called site
      specific modulation, incorporates systematic structural variations at a site of
      interest. Molecular modeling studies have suggested a structural basis for the
      affinity of native MDH for phenylpyruvate and a rationale for the improved
      catalytic activity that is observed with these new, modified phenyllactate
      dehydrogenases.

PMID- 10915785
TI  - Proximal promoter of the surfactant protein D gene: regulatory roles of AP-1,
      forkhead box, and GT box binding proteins.
AB  - Surfactant protein D (SP-D) plays roles in pulmonary host defense and surfactant
      homeostasis and is increased following lung injury. Because AP-1 proteins
      regulate cellular responses to diverse environmental stimuli, we hypothesized
      that the conserved AP-1 motif (at -109) and flanking sequences in the human SP-D
      promoter contribute to the regulation of SP-D expression. The AP-1 sequence
      specifically bound to fra-1, junD, and junB in H441 lung adenocarcinoma nuclear
      extracts. Mutagenesis of the AP-1 motif in a chloramphenicol acetyltransferase
      reporter construct containing 285 base pairs of upstream sequence nearly
      abolished promoter activity, and co-transfection of junD significantly increased
      wild type but not mutant promoter activity. The sequence immediately downstream
      of the AP-1 element contained a binding site for HNF-3 (FOXA), and simultaneous
      mutation of this site (fox-d) and an upstream FoxA binding site (-277, fox-u)
      caused a 4-fold reduction in chloramphenicol acetyltransferase activity.
      Immediately upstream of the AP-1-binding site, we identified a GT box-containing
      positive regulatory element. Despite finding regions of limited homology to the
      thyroid transcription factor 1-binding site, SP-D promoter activity did not
      require thyroid transcription factor 1. Thus, transcriptional regulation of SP-D
      gene expression involves complex interactions with ubiquitous and lineage
      dependent factors consistent with more generalized roles in innate immunity.

PMID- 10915787
TI  - Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters.
      Analysis of a delta-like domain.
AB  - Treatment of leukemic cells with phorbol 12-myristate 13-acetate (PMA) induces a
      short-lived phosphorylation and activation of stress-activated protein kinase
      (SAPK) and cellular differentiation. To investigate whether the rapid
      deactivation of SAPK results from dephosphorylation by dual-specificity
      phosphatases (DSPs), we studied regulation of the DSP hVH5 and its murine
      orthologue M3/6 in K562 human leukemia cells. PMA treatment rapidly induced hVH5
      transcripts in these cells, and induced expression of M3/6 completely inhibited
      PMA-stimulated phosphorylation of SAPK, suggesting a feedback loop to control
      SAPK activity. Using both stable cell lines and transient transfection we
      demonstrate that activation of SAPK rapidly stimulated phosphorylation of M3/6.
      This phosphorylation did not regulate the half-life of total cellular M3/6. hVH5
      and M3/6 shares with all sequenced mammalian DSPs an amino acid motif, XILPXLXL,
      located approximately 80 amino acids from the active site. The hVH5-M3/6
      sequence, RILPHLYL, shares significant homology with the SAPK binding site of the
      c-Jun protein, called the delta domain. This motif was found to be important for
      DSP function, because deletion of RILPHLYL inhibits SAPK-mediated phosphorylation
      of M3/6, and deletion of this sequence or mutation of the LYL portion blocks the
      ability of this phosphatase to dephosphorylate SAPK.

PMID- 10915788
TI  - Targeting of PYK2 to focal adhesions as a cellular mechanism for convergence
      between integrins and G protein-coupled receptor signaling cascades.
AB  - The non-receptor tyrosine kinase PYK2 appears to function at a point of
      convergence of integrins and certain G protein-coupled receptor (GPCR) signaling
      cascades. In this study, we provide evidence that translocation of PYK2 to focal
      adhesions is triggered both by cell adhesion to extracellular matrix proteins and
      by activation of the histamine GPCR. By using different mutants of PYK2 as green
      fluorescent fusion proteins, we show that the translocation of PYK2 to focal
      adhesions is not dependent on its catalytic activity but rather is mediated by
      its carboxyl-terminal domain. Translocation of PYK2 to focal adhesions was
      attributed to enhanced tyrosine phosphorylation of PYK2 and its association with
      the focal adhesion proteins paxillin and p130(Cas). Translocation of PYK2 to
      focal adhesions, as well as its tyrosine phosphorylation in response to histamine
      treatment, was abolished in the presence of protein kinase C inhibitors or
      cytochalasin D treatment, whereas activation of protein kinase C by phorbol ester
      resulted in focal adhesion targeting of PYK2 and its tyrosine phosphorylation in
      an integrin-clustering dependent manner. Overexpression of a wild-type PYK2
      enhanced ERK activation in response to histamine, whereas a kinase-deficient
      mutant substantially inhibited this response. Furthermore, inhibition of PYK2
      translocation to focal adhesions abolished ERK activation in response to
      histamine treatment. These results suggest that PYK2 apparently links between
      GPCRs and focal adhesion-dependent ERK activation and can provide the molecular
      basis underlying PYK2 function at a point of convergence between signaling
      pathways triggered by extracellular matrix proteins and certain GPCR agonists.

PMID- 10915789
TI  - Direct binding of hydroxylamine to the heme iron of Arthromyces ramosus
      peroxidase. Substrate analogue that inhibits compound I formation in a
      competetive manner.
AB  - The interaction of hydroxylamine (HA) with Arthromyces ramosus peroxidase (ARP)
      was investigated by kinetic, spectroscopic, and x-ray crystallographic
      techniques. HA inhibited the reaction of native ARP with H(2)O(2) in a
      competitive manner. Electron absorption and resonance Raman spectroscopic studies
      indicated that pentacoordinate high spin species of native ARP are converted to
      hexacoordinate low spin species upon the addition of HA, strongly suggesting the
      occurrence of a direct interaction of HA with ARP heme iron. Kinetic analysis
      exhibited that the apparent dissociation constant is 6.2 mm at pH 7.0 and that
      only one HA molecule likely binds to the vicinity of the heme. pH dependence of
      HA binding suggested that the nitrogen atom of HA could be involved in the
      interaction with the heme iron. X-ray crystallographic analysis of ARP in complex
      with HA at 2.0 A resolution revealed that the electron density ascribed to HA is
      located in the distal pocket between the heme iron and the distal His(56). HA
      seems to directly interact with the heme iron but is too far away to interact
      with Arg(52). In HA, it is likely that the nitrogen atom is coordinated to the
      heme iron and that hydroxyl group is hydrogen bonded to the distal His(56).

PMID- 10915790
TI  - alpha-Synuclein membrane interactions and lipid specificity.
AB  - With the discovery of missense mutations (A53T and A30P) in alpha-synuclein
      (alpha-Syn) in several families with early onset familial Parkinson's disease,
      alpha-Syn aggregation and fibril formation have been thought to play a role in
      the pathogenesis of alpha-synucleinopathies, such as Parkinson's disease,
      dementia with Lewy bodies, and multiple system atrophy. As previous reports have
      suggested that alpha-Syn plays a role in lipid transport and synaptic membrane
      biogenesis, we investigated whether alpha-Syn binds to a specific lipid ligand
      using thin layer chromatography overlay and examined the changes in its secondary
      structure using circular dichroism spectroscopy. alpha-Syn was found to bind to
      acidic phospholipid vesicles and this binding was significantly augmented by the
      presence of phosphatidylethanolamine, a neutral phospholipid. We further examined
      the interaction of alpha-Syn with lipids by in situ atomic force microscopy. The
      association of soluble wild-type alpha-Syn with planar lipid bilayers resulted in
      extensive bilayer disruption and the formation of amorphous aggregates and small
      fibrils. The A53T mutant alpha-Syn disrupted the lipid bilayers in a similar
      fashion but at a slower rate. These results suggest that alpha-Syn membrane
      interactions are physiologically important and the lipid composition of the
      cellular membranes may affect these interactions in vivo.

PMID- 10915791
TI  - Wnt signaling regulates the function of MyoD and myogenin.
AB  - The myogenic regulatory factors (MRFs), MyoD and myogenin, can induce myogenesis
      in a variety of cell lines but not efficiently in monolayer cultures of P19
      embryonal carcinoma stem cells. Aggregation of cells expressing MRFs, termed
      P19[MRF] cells, results in an approximately 30-fold enhancement of myogenesis.
      Here we examine molecular events occurring during P19 cell aggregation to
      identify potential mechanisms regulating MRF activity. Although myogenin protein
      was continually present in the nuclei of >90% of P19[myogenin] cells, only a
      fraction of these cells differentiated. Consequently, it appears that post
      translational regulation controls myogenin activity in a cell lineage-specific
      manner. A correlation was obtained between the expression of factors involved in
      somite patterning, including Wnt3a, Wnt5b, BMP-2/4, and Pax3, and the induction
      of myogenesis. Co-culturing P19[Wnt3a] cells with P19[MRF] cells in monolayer
      resulted in a 5- to 8-fold increase in myogenesis. Neither BMP-4 nor Pax3 was
      efficient in enhancing MRF activity in unaggregated P19 cultures. Furthermore,
      BMP-4 abrogated the enhanced myogenesis induced by Wnt signaling. Consequently,
      signaling events resulting from Wnt3a expression but not BMP-4 signaling or Pax3
      expression, regulate MRF function. Therefore, the P19 cell culture system can be
      used to study the link between somite patterning events and myogenesis.

PMID- 10915792
TI  - Identification of a common protein association region in the neuronal Cdk5
      activator.
AB  - Cyclin-dependent protein kinase 5 (Cdk5) depends on the association with neuronal
      Cdk5 activator (Nck5a) for kinase activity. A variety of cellular proteins have
      been shown to undergo high affinity association with Nck5a, including three novel
      proteins, C42, C48, and C53 found by a yeast two-hybrid screen (Ching, Y. P., Qi,
      Z., and Wang, J. H. (2000) Gene 242, 285-294). The three proteins show
      competitive binding to Nck5a suggesting that they bind at a common site. The
      binding site has been mapped to a region of 26 amino acid residues (residues 145
      to 170) at the N-terminal boundary of the kinase activation domain of Nck5a. This
      region of Nck5a contains an amphipathic alpha-helix whose hydrophobic face is
      involved in Cdk5 activation (Chin, K. T., Ohki, S, Tang, D., Cheng, H. C., Wang,
      J. H. , and Zhang, M. (1999) J. Biol. Chem. 274, 7120-7127). Several lines of
      evidence suggest that Nck5a interacts with the binding proteins at the
      hydrophilic face of the amphipathic alpha-helix. First, the Nck5a-(145-170)
      peptide can bind Cdk5 and Nck5a-binding proteins simultaneously. Second, the
      association of Nck5a-(145-170) to C48 can be markedly reduced by high ionic
      strength whereas the interaction between Nck5a and Cdk5 is not affected. Third,
      substitution of Glu(157) by glutamine in Nck5a-(145-170) abolishes the peptide's
      ability to bind to the three Nck5a-binding proteins without diminishing its Cdk5
      binding activity.

PMID- 10915793
TI  - Accumulation of mitochondrial P450MT2, NH(2)-terminal truncated cytochrome
      P4501A1 in rat brain during chronic treatment with beta-naphthoflavone. A role in
      the metabolism of neuroactive drugs.
AB  - The biochemical and molecular characteristics of cytochrome P4501A1 targeted to
      rat brain mitochondria was studied to determine the generality of the targeting
      mechanism previously described for mitochondrial cytochrome P450MT2 (P450MT2)
      from rat liver. In rat brain and C6 glioma cells chronically exposed to beta
      naphoflavone (BNF), P450MT2 content reached 50 and 95% of the total cellular
      pool, respectively. P450MT2 from 10 days of BNF-treated rat brain was purified to
      over 85% purity using hydrophobic chromatography followed by adrenodoxin affinity
      binding. Purified brain P450MT2 consisted of two distinct molecular species with
      NH(2) termini identical to liver mitochondrial forms. These results confirm the
      specificity of endoprotease-processing sites. The purified P450MT2 showed a
      preference for adrenodoxin + adrenodoxin reductase electron donor system and
      exhibited high erythromycin N-demethylation activity. Brain mitoplasts from 10
      day BNF-treated rats and also purified P450MT2 exhibited high N-demethylation
      activities for a number of neuroactive drugs, including trycyclic anti
      depressants, anti-convulsants, and opiates. At 10 days of BNF treatment, the
      mitochondrial metabolism of these neuroactive drugs represented about 85% of the
      total tissue activity. These results provide new insights on the role of P450MT2
      in modulating the pharmacological potencies of different neuroactive drugs in
      chronically exposed individuals.

PMID- 10915794
TI  - The amino-terminal domain of the B subunit of vacuolar H+-ATPase contains a
      filamentous actin binding site.
AB  - Vacuolar H(+)-ATPase (V-ATPase) binds actin filaments with high affinity (K(d) =
      55 nm; Lee, B. S., Gluck, S. L., and Holliday, L. S. (1999) J. Biol. Chem. 274,
      29164-29171). We have proposed that this interaction is an important mechanism
      controlling transport of V-ATPase from the cytoplasm to the plasma membrane of
      osteoclasts. Here we show that both the B1 (kidney) and B2 (brain) isoforms of
      the B subunit of V-ATPase contain a microfilament binding site in their amino
      terminal domain. In pelleting assays containing actin filaments and partially
      disrupted V-ATPase, B subunits were found in greater abundance in actin pellets
      than were other V-ATPase subunits, suggesting that the B subunit contained an F
      actin binding site. In overlay assays, biotinylated actin filaments also bound to
      the B subunit. A fusion protein containing the amino-terminal half of B1 subunit
      bound actin filaments tightly, but fusion proteins containing the carboxyl
      terminal half of B1 subunit, or the full-length E subunit, did not bind F-actin.
      Fusion proteins containing the amino-terminal 106 amino acids of the B1 isoform
      or the amino-terminal 112 amino acids of the B2 isoform bound filamentous actin
      with K(d) values of 130 and 190 nm, respectively, and approached saturation at 1
      mol of fusion protein/mol of filamentous actin. The B1 and B2 amino-terminal
      fusion proteins competed with V-ATPase for binding to filamentous actin. In
      summary, binding sites for F-actin are present in the amino-terminal domains of
      both isoforms of the B subunit, and likely are responsible for the interaction
      between V-ATPase and actin filaments in vivo.

PMID- 10915795
TI  - The Rb-CDK4/6 signaling pathway is critical in neural precursor cell cycle
      regulation.
AB  - The tumor suppressor, retinoblastoma (Rb), is involved in both terminal mitosis
      and neuronal differentiation. We hypothesized that activation of the Rb pathway
      would induce cell cycle arrest in primary neural precursor cells, independent of
      the proposed function of cyclin-dependent kinases 4/6 (CDK4/6) to sequester the
      CIP/KIP CDK inhibitors (CKIs) p21 and p27 from CDK2. We expressed dominant
      negative adenovirus mutants of CDKs 2, 4, and 6 (dnCDK2, dnCDK4, and dnCDK6) in
      neural progenitor cells derived from E12.5 wild type and Rb-deficient mouse
      embryos. In contrast to previous studies, our results demonstrate that in
      addition to dnCDK2, the dnCDK4/6 mutants can induce growth arrest. Moreover, the
      dnCDK4/6-mediated inhibition is Rb-dependent. The dnCDK2 partially inhibited cell
      growth in Rb-deficient cells, suggesting that CDK2 may have additional targets. A
      previously proposed function of CDK4/6 is CKI sequestration, thereby preventing
      the resulting inhibition of CDK2, believed to be the key regulator of cell cycle.
      However, our immunoprecipitations revealed that the dominant negative CDK mutants
      could arrest cell growth despite their interaction with p21 and p27. Taken
      together, our results demonstrate that both CDK2 and CDK4/6 are crucial for cell
      cycle regulation. Furthermore, our data underscore the importance of the Rb
      regulatory pathway in neuronal development and cell cycle regulation, independent
      of CKI sequestration.

PMID- 10915796
TI  - Characterization of a cDNA encoding a novel human Golgi alpha 1, 2-mannosidase
      (IC) involved in N-glycan biosynthesis.
AB  - A human cDNA encoding a 70.9-kDa type II membrane protein with sequence
      similarity to class I alpha1,2-mannosidases was isolated. The enzymatic
      properties of the novel alpha1,2-mannosidase IC were studied by expressing its
      catalytic domain in Pichia pastoris as a secreted glycoprotein. alpha1,2
      Mannosidase IC sequentially hydrolyzes the alpha1,2-linked mannose residues of
      [(3)H]mannose-labeled Man(9)GlcNAc to form [(3)H]Man(6)GlcNAc and a small amount
      of [(3)H]Man(5)GlcNAc. The enzyme requires calcium for activity and is inhibited
      by both 1-deoxymannojirimycin and kifunensine. The order of mannose removal was
      determined by separating oligosaccharide isomers formed from pyridylaminated
      Man(9)GlcNAc(2) by high performance liquid chromatography. The terminal alpha1,2
      linked mannose residue from the middle branch is the last mannose removed by the
      enzyme. This residue is the mannose cleaved from Man(9)GlcNAc(2) by the
      endoplasmic reticulum alpha1, 2-mannosidase I to form Man(8)GlcNAc(2) isomer B.
      The order of mannose hydrolysis from either pyridylaminated Man(9)GlcNAc(2) or
      Man(8)GlcNAc(2) isomer B differs from that previously reported for mammalian
      Golgi alpha1,2-mannosidases IA and IB. The full-length alpha1,2-mannosidase IC
      was localized to the Golgi of MDBK and MDCK cells by indirect immunofluorescence.
      Northern blot analysis showed tissue-specific expression of a major transcript of
      3.8 kilobase pairs. The expression pattern is different from that of human Golgi
      alpha1,2-mannosidases IA and IB. Therefore, the human genome contains at least
      three differentially regulated Golgi alpha1, 2-mannosidase genes encoding enzymes
      with similar, but not identical specificities.

PMID- 10915797
TI  - Dimer stability as a determinant of differential DNA binding activity of Stat3
      isoforms.
AB  - Stat3alpha and Stat3beta are two Stat3 isoforms with marked quantitative
      differences in their DNA binding activities. To examine the molecular basis of
      the differential DNA binding activities, we measured DNA binding strength and
      dimer stability, two possible mechanisms responsible for these differences.
      Stat3alpha and Stat3beta showed no difference in DNA binding strength, i.e. they
      had similar association and dissociation rates for DNA binding. However,
      competition analyses performed with dissociating reagents including an anti
      phosphotyrosine antibody, SH2 domain protein, and a phosphopeptide demonstrated
      that Stat3beta dimers are more stable than Stat3alpha dimers. We report here that
      dimer stability of activated forms plays a critical role in determining DNA
      binding activity of Stat3 isoforms. We found that C-terminal deletions of
      Stat3alpha increased both DNA binding activity and dimer stability of Stat3alpha.
      Our findings suggest that the acidic C-terminal region of Stat3alpha does not
      interfere with the DNA binding of activated Stat3alpha dimers, but destabilizes
      the dimeric forms of Stat3alpha. We propose that dimer stability described in
      vitro may be the underlying mechanism of in vivo stability of activated Stat3
      proteins, regulating dephosphorylation of tyrosine 705.

PMID- 10915798
TI  - The postmitotic growth suppressor necdin interacts with a calcium-binding protein
      (NEFA) in neuronal cytoplasm.
AB  - Necdin, a growth suppressor expressed predominantly in postmitotic neurons,
      interacts with viral oncoproteins and cellular transcription factors E2F1 and
      p53. In search of other cellular targets of necdin, we screened cDNA libraries
      from neurally differentiated murine embryonal carcinoma P19 cells and adult rat
      brain by the yeast two-hybrid assay. We isolated cDNAs encoding partial sequences
      of mouse NEFA and rat nucleobindin (CALNUC), which are Ca(2+)-binding proteins
      possessing similar domain structures. Necdin interacted with NEFA via a domain
      encompassing two EF hand motifs, which had Ca(2+) binding activity as determined
      by (45)Ca(2+) overlay. NEFA was widely distributed in mouse organs, whereas
      necdin was expressed predominantly in the brain and skeletal muscle. In mouse
      brain in vivo, NEFA was localized in neuronal perikarya and dendrites. By
      immunoelectron microscopy, NEFA was localized to the cisternae of the endoplasmic
      reticulum and nuclear envelope in brain neurons. NEFA-green fluorescent protein
      (GFP) fusion protein expressed in neuroblastoma N1E-115 cells was retained in the
      cytoplasm and partly secreted into the culture medium. Necdin enhanced the
      cytoplasmic retention of NEFA-GFP and potentiated the effect of NEFA-GFP on
      caffeine-evoked elevation of cytosolic Ca(2+) levels. Thus, necdin and NEFA might
      be involved in Ca(2+) homeostasis in neuronal cytoplasm.

PMID- 10915799
TI  - Folding and maturation of tyrosinase-related protein-1 are regulated by the post
      translational formation of disulfide bonds and by N-glycan processing.
AB  - In this study we have explored the endoplasmic reticulum associated events
      accompanying the maturation of the tyrosinase-related protein-1 (TRP-1) nascent
      chain synthesized in mouse melanoma cells. We show that TRP-1 folding process
      occurs much more rapidly than for tyrosinase, a highly homologous protein, being
      completed post-translationally by the formation of critical disulfide bonds. In
      cells pretreated with dithiothreitol (DTT), unfolded TRP-1 is retained in the
      endoplasmic reticulum by a prolonged interaction with calnexin and BiP before
      being targeted for degradation. The TRP-1 chain was able to fold into DTT
      resistant conformations both in the presence or absence of alpha-glucosidase
      inhibitors, but folding occurred through different pathways. During the normal
      folding pathway, TRP-1 interacts with calnexin. In the presence of alpha
      glucosidase inhibitors, the interaction with calnexin is prevented, with TRP-1
      folding being assisted by BiP. In this case, the process has similar kinetics to
      that of untreated TRP-1 and yields a compact form insensitive to DTT as well.
      However, this form has different thermal denaturation properties than the native
      conformation. We conclude that disulfide bridge burring is crucial for the TRP-1
      export. This suggests that although various folding pathways may complete this
      process, the native form may be acquired only through the normal unperturbed
      pathway.

PMID- 10915801
TI  - Presenilin-1 and -2 are molecular targets for gamma-secretase inhibitors.
AB  - Presenilins are integral membrane protein involved in the production of amyloid
      beta-protein. Mutations of the presenilin-1 and -2 gene are associated with
      familial Alzheimer's disease and are thought to alter gamma-secretase cleavage of
      the beta-amyloid precursor protein, leading to increased production of longer and
      more amyloidogenic forms of A beta, the 4-kDa beta-peptide. Here, we show that
      radiolabeled gamma-secretase inhibitors bind to mammalian cell membranes, and a
      benzophenone analog specifically photocross-links three major membrane
      polypeptides. A positive correlation is observed among these compounds for
      inhibition of cellular A beta formation, inhibition of membrane binding and cross
      linking. Immunological techniques establish N- and C-terminal fragments of
      presenilin-1 as specifically cross-linked polypeptides. Furthermore, binding of
      gamma-secretase inhibitors to embryonic membranes derived from presenilin-1
      knockout embryos is reduced in a gene dose-dependent manner. In addition, C
      terminal fragments of presenilin-2 are specifically cross-linked. Taken together,
      these results indicate that potent and selective gamma-secretase inhibitors block
      A beta formation by binding to presenilin-1 and -2.

PMID- 10915800
TI  - MAP kinases Erk1/2 phosphorylate sterol regulatory element-binding protein
      (SREBP)-1a at serine 117 in vitro.
AB  - Sterol regulatory element-binding protein (SREBP)-1a is a transcription factor
      sensing cellular cholesterol levels and integrating gene regulatory signals
      mediated by MAP kinase cascades. Here we report the identification of serine 117
      in SREBP-1a as the major phosphorylation site of the MAP kinases Erk1/2. This
      site was identified by nanoelectrospray mass spectrometry and peptide sequencing
      of recombinant fusion proteins phosphorylated by Erk1/2 in vitro. Serine 117 was
      verified as the major phosphorylation site by in vitro mutagenesis. Mutation of
      serine 117 to alanine abolished Erk2-mediated phosphorylation in vitro and the
      MAP kinase-related transcriptional activation of SREBP-1a by insulin and platelet
      derived growth factor in vivo. Our data indicate that the MAP kinase-mediated
      effects on SREBP-1a-regulated target genes are linked to this phosphorylation
      site.

PMID- 10915802
TI  - Activation of protein kinase C stimulates the dephosphorylation of natriuretic
      peptide receptor-B at a single serine residue: a possible mechanism of
      heterologous desensitization.
AB  - The binding of atrial natriuretic peptide and C-type natriuretic peptide (CNP) to
      the guanylyl cyclase-linked natriuretic peptide receptors A and B (NPR-A and -B),
      respectively, stimulates increases in intracellular cGMP concentrations. The
      vasoactive peptides vasopressin, angiotensin II, and endothelin inhibit
      natriuretic peptide-dependent cGMP elevations by activating protein kinase C
      (PKC). Recently, we identified six in vivo phosphorylation sites for NPR-A and
      five sites for NPR-B and demonstrated that the phosphorylation of these sites is
      required for ligand-dependent receptor activation. Here, we show that phorbol 12
      myristate 13-acetate, a direct activator of PKC, causes the dephosphorylation and
      desensitization of NPR-B. In contrast to the CNP-dependent desensitization
      process, which results in coordinate dephosphorylation of all five sites in the
      receptor, phorbol 12-myristate 13-acetate treatment causes the dephosphorylation
      of only one site, which we have identified as Ser(523). The conversion of this
      residue to alanine or glutamate did not reduce the amount of mature receptor
      protein as indicated by detergent-dependent guanylyl cyclase activities or
      Western blot analysis but completely blocked the ability of PKC to induce the
      dephosphorylation and desensitization of NPR-B. Thus, in contrast to previous
      reports suggesting that PKC directly phosphorylates and inhibits guanylyl cyclase
      linked natriuretic peptide receptors, we show that PKC-dependent
      dephosphorylation of NPR-B at Ser(523) provides a possible molecular explanation
      for how pressor hormones inhibit CNP signaling.

PMID- 10915803
TI  - Multiple distant amino acid residues present in the serpentine region of the
      follitropin receptor modulate the rate of agonist-induced internalization.
AB  - The amino acid sequences of the human (h) and rat (r) follitropin receptors
      (FSHR) are approximately 89% identical, but the half-time of internalization of
      agonist mediated by the rFSHR is approximately 3 times faster than that of the
      hFSHR. Chimeras of the hFSHR and the rFSHR showed that this difference in rate is
      dictated mostly by the serpentine domain. Further analysis identified six
      residues, two non-contiguous residues in the transmembrane helix 4 (Leu/Thr in
      the rFSHR and Met/Ile in the hFSHR), three non-contiguous residues in the third
      intracellular loop (Thr/Thr/Lys in the rFSHR and Ile/Asn/Arg in the hFSHR), and
      one in transmembrane helix 7 (Tyr in the rFSHR and His in the hFSHR) that are
      fully responsible for the difference in the rates of internalization of the hFSHR
      and the rFSHR.

PMID- 10915804
TI  - Transcriptional activation of an Escherichia coli copper efflux regulon by the
      chromosomal MerR homologue, cueR.
AB  - Because copper ions are both essential cofactors and cytotoxic agents, the net
      accumulation of this element in a cell must be carefully balanced. Depending upon
      the cellular copper status, copper ions must either be imported or ejected. CopA,
      the principal copper efflux ATPase in Escherichia coli, is induced by elevated
      copper in the medium, but the copper-sensing regulatory factor is unknown.
      Inspection of the copA promoter reveals signature elements of promoters
      controlled by metalloregulatory proteins in the MerR family. These same elements
      are also present upstream of yacK, which encodes a putative multi-copper oxidase.
      Homologues of YacK are found in copper resistance determinants that facilitate
      copper efflux. Here we show by targeted gene deletion and promoter fusion assays
      that both copA and yacK are regulated in a copper-responsive manner by the MerR
      homologue, ybbI. We have designated ybbI as cueR for the Cu efflux regulator.
      This represents the first example of a copper-responsive regulon on the E. coli
      chromosome and further extends the roles of MerR family members in prokaryotic
      stress response.

PMID- 10915805
TI  - Specific amygdaloid nuclei are involved in suppression or propagation of
      epileptiform activity during transition stage between oral automatisms and
      generalized clonic seizures.
AB  - Kindling is a model of the neural plasticity that occurs following stimulation to
      the brain, which can result in epileptogenesis. The amygdala (Am), one of the
      most sensitive structures from which to induce electrical kindling, is comprised
      of distinct nuclei that possess differences in threshold for seizure initiation,
      unique cellular and molecular morphology, and specific neuroanatomical
      connections within the amygdala and, to other cortical and subcortical brain
      structures. The aim of this study was to map the spread of epileptiform activity
      throughout the ipsilateral and contralateral hemispheres during the transition
      stage between oral automatisms and generalized clonic seizures, by measuring
      changes in mRNA expression for c-fos, NGFI-A, and BDNF. The stimulating electrode
      was implanted in either the basolateral (BL) or the lateral (CeL) or medial (CeM)
      subdivisions of the central nucleus of the amygdala. The rats were kindled once
      daily using afterdischarge-threshold electrical stimulation until the first
      forelimb clonic seizure was induced. They were sacrificed 30 min later, and their
      brains were prepared for in situ hybridization to measure mRNA expression of c
      fos, NGFI-A and BDNF. The results demonstrate that: (1) the threshold to elicit
      an afterdischarge from the BL was lower than that of either the medial (CeM) or
      lateral (CeL) subdivisions of the Ce, which did not differ from each other; (2)
      the patterns of mRNA expression for c-fos, NGFI-A and BDNF were highly similar to
      each other when the stimulation site was the BL or the CeL, and included mainly
      limbic cortical and subcortical areas ipsilateral to the electrode; (3) c-fos was
      the only probe to be expressed in the contralateral hemisphere following the
      first motor seizure, and the pattern of its expression reflected a subset of
      structures recruited in the ipsilateral hemisphere including the claustrum,
      insular and perirhinal cortices; (4) unexpectedly, stimulation of the CeM
      elicited seizures and afterdischarges of shorter duration than those evoked by
      stimulation of the BL or CeL, and failed to increase mRNA expression for any of
      the probes in the hippocampus or in the contralateral hemisphere. A
      neuroanatomical model of Am-induced seizure propagation is proposed suggesting
      that the Claust-Ins-PRh play a pivotal role during the transition between oral
      automatisms and generalized clonic convulsions.

PMID- 10915806
TI  - Modeling adolescent nicotine exposure: effects on cholinergic systems in rat
      brain regions.
AB  - Smoking among teenagers is increasing and the initiation of tobacco use during
      adolescence is associated with subsequently higher cigarette consumption and
      lower rates of quitting. Few animal studies have addressed whether adolescent
      nicotine exposure exerts unique or lasting effects on brain structure or
      function. Initial investigations with a rat model of adolescent nicotine exposure
      have demonstrated that the vulnerable developmental period for nicotine-induced
      brain cell damage extends into adolescence. In the current study, we examined the
      effect of nicotine on cholinergic systems in male and female adolescent rats with
      an infusion paradigm designed to match the plasma levels found in human smokers
      or in users of the transdermal nicotine patch. Choline acetyltransferase activity
      (ChAT) and [3H]hemicholinium-3 binding (HC-3) were monitored; ChAT is a static
      marker that closely reflects the density of cholinergic innervation, whereas HC-3
      binding, which labels the presynaptic high-affinity choline transporter, is
      responsive additionally to nerve impulse activity. Measurements were carried out
      in the midbrain, the region most closely involved in reward and addiction
      pathways, as well as in the cerebral cortex and hippocampus. During nicotine
      treatment and for 1 month after the termination of treatment, ChAT activity was
      reduced significantly in the midbrain but not in the other regions. HC-3 binding
      showed a substantial increase during the course of nicotine treatment and again,
      the effect was limited to the midbrain. Midbrain values returned to normal
      immediately after the cessation of nicotine exposure and then showed a
      subsequent, transient suppression of activity. Although the cerebral cortex
      showed little or no change in HC-3 binding during or after nicotine
      administration, activity was reduced persistently in the hippocampus. The
      regionally-selective effects of adolescent nicotine treatment on cholinergic
      systems support the concept that adolescence is a vulnerable developmental period
      for ultimate effects on behavior.

PMID- 10915807
TI  - Altered mechanisms of motor-evoked potential generation after transient focal
      cerebral ischemia in the rat: implications for transcranial magnetic stimulation.
AB  - We recently demonstrated that a long-lasting transmission defect in cortical
      synapses caused motor dysfunction after brief middle cerebral artery (MCA)
      occlusion in the rat despite rapid recovery of axons. In this experimental study,
      we have examined the impact of differential recovery of synapses and axons on
      generation of motor-evoked potentials (MEP) recorded from contralateral paralyzed
      and ipsilateral unaffected muscles, to gain insight into mechanisms of MEPs
      recorded from stroke patients by transcranial magnetic stimulation (TMS). MEPs
      generated by focal electrical stimulation of the forelimb area of motor cortex
      were simultaneously recorded from the brain stem, contra- and ipsilateral
      forelimb and contralateral hindlimb muscles in rats subjected to transient MCA
      occlusion. The effect of ischemia on cortical activity and axonal conduction was
      differentially studied by proximal or distal occlusion of the MCA. Regional
      cerebral blood flow changes in the forelimb area were monitored by laser-Doppler
      flowmetry during ischemia and reperfusion. In addition, synaptic transmission
      within the forelimb area of motor cortex was examined by intracellular and
      extracellular recording of potentials generated by stimulation of the premotor
      area. No MEP response was recorded during ischemia. Upon reperfusion: (i) motor
      axons readily regained their excitability and cortical stimulation caused
      successive pyramidal volleys (recorded as D waves from the brain stem) and a MEP
      from contralateral paralytic muscles although synaptic activation of motor
      pathways was not feasible; (ii) the amplitude of pyramidal volley was increased;
      (iii) MEPs with a longer latency were recorded from the ipsilateral forelimb. In
      conclusion, differential recovery of synapses and axons after ischemia may
      account for some previously unexplained findings (such as preserved MEPs in
      paralysed muscles) observed in cortical stimulation studies of stroke patients.

PMID- 10915808
TI  - Serotonin 5-HT(2) receptors activate local GABA inhibitory inputs to serotonergic
      neurons of the dorsal raphe nucleus.
AB  - The purpose of the present study was to characterize the synaptic currents
      induced by bath-applied serotonin (5-HT) in 5-HT cells of the dorsal raphe
      nucleus (DRN) and to determine which 5-HT receptor subtypes mediate these
      effects. In rat brain slices, 5-HT induced a concentration-dependent increase in
      the frequency of inhibitory postsynaptic currents (IPSCs) in 5-HT neurons
      recorded intracellularly in the ventral part of the DRN (EC(50): 86 microM); 5-HT
      also increased IPSC amplitude. These effects were blocked by the GABA(A) receptor
      antagonist, bicuculline (10 microM) and by the fast sodium channel blocker, TTX,
      suggesting that 5-HT had increased impulse flow in local GABAergic neurons. DAMGO
      (300 nM), a selective mu-agonist, markedly suppressed the increase in IPSC
      frequency induced by 5-HT (100 microM) in the DRN. A near maximal concentration
      of the selective 5-HT(2A) antagonist, MDL100,907 (30 nM), produced a large
      reduction ( approximately 70%) in the increase in IPSC frequency induced by 100
      microM 5-HT; SB242,084 (30 nM), a selective 5-HT(2C) antagonist, was less
      effective ( approximately 24% reduction). Combined drug application suppressed
      the increase in 5-HT-induced IPSC frequency almost completely, suggesting
      involvement of both 5-HT(2A) and 5-HT(2C) receptors. Unexpectedly, the
      phenethylamine hallucinogen, DOI, a partial agonist at 5-HT(2A/2C) receptors,
      caused a greater increase (+334%) in IPSC frequency than did 5-HT 100 microM
      (+80%). This result may be explained by an opposing 5-HT(1A) inhibitory effect
      since the selective 5-HT(1A) antagonist, WAY-100635, enhanced the 5-HT-induced
      increase in IPSCs. These results indicate that within the DRN-PAG area there may
      be a negative feedback loop in which 5-HT induces an increase in IPSC frequency
      in 5-HT cells by exciting GABAergic interneurons in the DRN via 5-HT(2A) and, to
      a lesser extent, 5-HT(2C) receptors. Increased GABA tone may explain the previous
      observation of an indirect suppression of firing of a subpopulation of 5-HT cells
      in the DRN induced by phenethylamine hallucinogens in vivo.

PMID- 10915809
TI  - 4-aminopyridine, a specific blocker of K(+) channels, inhibited inward Na(+)
      current in rat cerebellar granule cells.
AB  - The effects of 4-aminopyridine (4-AP), a specific blocker of outward K(+)
      current, on voltage-activated transient outward K(+) current (I(K(A))) and inward
      Na(+) current (I(Na)) were investigated on cultured rat cerebellar granule cells
      using the whole cell voltage-clamp technique. At the concentration of 1-5 mM, 4
      AP inhibited both I(K(A)) and I(Na). It reduced the amplitude of peak Na(+)
      current without significant alteration of the steady-state activation and
      inactivation properties. The inhibitory effect was not enhanced by repeated
      depolarizing pulses (0.5 or 0.1 Hz), suggesting that the binding affinity of 4-AP
      on Na(+) channels is state-independent. In contrast, the effect of 4-AP on Na(+)
      channels appeared to be voltage-dependent, the weaker inhibition occurred at more
      depolarization. Moreover, 4-AP slowed both the activation and inactivation
      kinetics of Na(+) current. These effects were similar to those induced by alpha
      scorpion toxin and sea anemone toxins on Na(+) channels in other cell model. Our
      data demonstrate for the first time that 4-AP is able to block not only A-type
      K(+) channels, but also Na(+) channels in rat cerebellar granule cells. It is
      concluded that the inhibition exerted by 4-AP on Na(+) current likely differs
      from that provoked by local anesthetics. The possibility that the binding site of
      neurotoxin receptor 3 may be involved is discussed.

PMID- 10915810
TI  - Anti-nociceptive effects of calcitonin gene-related peptide in nucleus raphe
      magnus of rats: an effect attenuated by naloxone.
AB  - The present study investigated the role of calcitonin gene-related peptide (CGRP)
      on nociception in nucleus raphe magnus (NRM) and the interaction between CGRP and
      opioid peptides in NRM of rats. CGRP-like immunoreactivity was found at a
      concentration of 6.0+/-0. 77 pmol/g in NRM tissue of ten samples of rats,
      suggesting that it may contribute to physiological responses orchestrated by the
      NRM. The hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation
      increased significantly after intra-NRM administration of 0.5 or 1 nmol of CGRP
      in rats, but not 0.25 nmol. The anti-nociceptive effect induced by CGRP was
      antagonized by following intra-NRM injection of 1 nmol of the CGRP receptor
      antagonist CGRP8-37. Furthermore, the CGRP-induced anti-nociceptive effect was
      attenuated by following intra-NRM administration of 6 nmol of naloxone. The
      results indicate that CGRP and its receptors play an important role in anti
      nociception, and there is a possible interaction between CGRP and opioid peptides
      in NRM of rats.

PMID- 10915811
TI  - Distributed neurodegenerative changes 2-28 days after ventral hippocampal
      excitotoxic lesions in rats.
AB  - An enhanced sensitivity to the behavioral effects of dopamine (DA) agonists in
      adult rats occurs after cytotoxic lesions of the ventral hippocampus (vHPC).
      While some of these behavioral changes may model specific abnormalities in
      schizophrenia patients, little is known about the cellular events that underlie
      vHPC lesion-induced behavioral DA 'supersensitivity'. Neuropathological
      consequences of excitotoxin lesions of the vHPC were investigated in this study.
      Adult male rats received vehicle or ibotenic acid infusions into the vHPC, using
      parameters that produce an enhanced sensitivity to the prepulse inhibition
      disruptive effects of the DA agonist apomorphine, 1 month post-lesion. A total of
      27 rats were sacrificed, 2, 7, 14, 21 or 28 days post-lesion. Amino-cupric-silver
      staining demonstrated degenerative changes throughout the hippocampus, and in
      hippocampal efferent projections to forebrain structures, including the septal
      nucleus and nucleus accumbens (NAC), and within the olfactory tubercle (OT) and
      orbital cortex. Silver-impregnated fibers were identified in the substantia nigra
      reticulata (SNr), NAC, OT, septum and orbital cortex. Some degenerative changes
      were noted at the earliest time point (2 days post-lesion), while others were
      delayed in appearance. Adjacent sections stained for tyrosine hydroxylase (TH)
      immunocytochemistry revealed reduced TH labeling through forebrain DA terminal
      fields 28 days, but not 14 days after VH lesions. Excitotoxic lesions of the vHPC
      result in distributed neurotoxic changes in subcortical and cortical brain
      regions; these changes may contribute to the delayed emergence of DA-mediated
      behavioral abnormalities in these animals.

PMID- 10915812
TI  - Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle
      cerebral artery.
AB  - The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin
      system. The present study was designed to characterize the role of endothelium in
      relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine
      middle cerebral arteries were suspended in organ chambers for isometric force
      recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were
      assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP,
      3x10(-6) to 10(-5) mol/l), angiotensin-(1-7) (10(-9) to 3x10(-5) mol/l) caused
      concentration-dependent relaxations in arteries with endothelium, but not in
      endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation
      of cGMP. Nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester
      (L-NAME, 3x10(-4) mol/l), and selective soluble guanylate cyclase inhibitor, 1 H
      [1,2, 4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ, 3x10(-6) mol/l), abolished
      angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan
      (10(-5) mol/l), PD 123319 (10(-5) mol/l), [Sar(1),Thr(8)]-angiotensin II (10(-5)
      mol/l) [Sar(1),Val(5), Ala(8)]-angiotensin II (10(-5) mol/l) or [7-D-Ala]
      angiotensin 1-7 (10(-6) mol/l) did not affect these relaxations. However,
      angiotensin-converting enzyme inhibitor, captopril (10(-5) mol/l) augmented
      relaxations to angiotensin-(1-7). Finally, bradykinin B(2) receptor antagonist,
      [D-Arg(0),Hyp(3),Thi(5),D-Tic(7), Oic(8)]-bradykinin (HOE 140, 5x10(-8) mol/l)
      significantly reduced the effect of angiotensin-(1-7), while bradykinin B(1)
      receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin (6x10(-9) mol/l) did not
      influence the vascular response to the heptapeptide. These findings indicate that
      (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by
      the release of nitric oxide from endothelial cells, (2) angiotensin receptors do
      not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this
      effect appears to be dependent on activation of local production of kinins. Our
      studies support the concept that angiotensin-(1-7), as a natural vasodilator
      hormone, may counterbalance the hemodynamic actions of angiotensin II.

PMID- 10915813
TI  - Effects of blockade of voltage-sensitive Ca(2+)/Na(+) channels by a novel
      phenylpyrimidine derivative, NS-7, on CREB phosphorylation in focal cerebral
      ischemia in the rat.
AB  - NS-7 is a novel blocker of voltage-sensitive Ca(2+) and Na(+) channels, and it
      significantly reduces infarct size after occlusion of the middle cerebral artery.
      Persistent activation of cyclic AMP response element binding protein (CREB),
      which can be induced by increase in intracellular Ca(2+) concentrations or other
      second messengers, has recently been found to be closely associated with neuronal
      survival in cerebral ischemia. The present study was therefore undertaken to
      evaluate the neuroprotective effects of NS-7 by analyzing changes in CREB
      phosphorylation in a focal cerebral ischemia model. CREB phosphorylation in the
      brain of rats was investigated immunohistochemically at 3.5-48-h recirculation
      after 1. 5-h occlusion of the middle cerebral artery. NS-7 (1 mg/kg; NS-7 group)
      or saline (saline group) was intravenously injected 5 min after the start of
      recirculation. The NS-7 group showed significantly milder activation of CREB
      phosphorylation in various cortical regions after 3.5 h of recirculation than the
      saline group. The inner border zone of ischemia in the NS-7 group subsequently
      exhibited a moderate, but persistent, increase in number of phosphorylated CREB
      positive neurons with no apparent histological damage. By contrast, the saline
      group displayed a marked, but only transient, increase in number of
      immunopositive neurons in this border zone after 3.5 h of recirculation, and this
      was followed by clear suppression of CREB phosphorylation and subsequent loss of
      normal neurons. These findings suggest that: (1) the marked enhancement of CREB
      phosphorylation in the acute post-ischemic phase may be triggered largely by an
      influx of calcium ions as a result of activation of the voltage-sensitive Ca(2+)
      and Na(+) channels; and that (2) the neuroprotective effects of NS-7 may be
      accompanied by persistent activation of CREB phosphorylation in the inner border
      zone of ischemia.

PMID- 10915814
TI  - alpha-eudesmol, a P/Q-type Ca(2+) channel blocker, inhibits neurogenic
      vasodilation and extravasation following electrical stimulation of trigeminal
      ganglion.
AB  - In this study, we investigated the effect of alpha-eudesmol, which potently
      inhibits the presynaptic omega-agatoxin IVA-sensitive (P/Q-type) Ca(2+) channel,
      on neurogenic inflammation following electrical stimulation of rat trigeminal
      ganglion. Treatment with alpha-eudesmol (0.1-1 mg/kg. i.v.) dose-dependently
      attenuated neurogenic vasodilation in facial skin monitored by a laser Doppler
      flowmetry. In addition, alpha-eudesmol (1 mg/kg. i.v.) significantly decreased
      dural plasma extravasation in analysis using Evans blue as a plasma marker. On
      the other hand, alpha-eudesmol (1 mg/kg, i.v.) did not affect mean arterial blood
      pressure in rats. The calcitonin gene-related peptide (CGRP) and substance P (SP)
      released from activated sensory nerves have recently been suggested to be
      associated with the neurogenic inflammation. In this study, we also showed that
      alpha-eudesmol (0.45-45 microM) concentration-dependently inhibits the
      depolarization-evoked CGRP and SP release from sensory nerve terminals in spinal
      cord slices. These results indicate that the anti-neurogenic inflammation action
      of alpha-eudesmol, which does not affect the cardiovascular system, may be due to
      its presynaptic inhibition of the neuropeptide release from perivascular
      trigeminal terminals. We also suggest that the omega-agatoxin IVA-sensitive
      Ca(2+) channel blocker, alpha-eudesmol, may become useful for the treatment of
      the neurogenic inflammation in the trigemino-vascular system such as migraine.

PMID- 10915815
TI  - Effects of task context and fluctuations of attention on neural activity
      supporting performance of the stroop task.
AB  - The influence of task context and transient fluctuations in attentional control
      on neural processes supporting performance of the Stroop task was investigated
      using event-related brain potentials. Task context was manipulated by varying the
      proportion of congruent and incongruent trials across different blocks of trials,
      and fluctuations of attentional control were considered by examining differences
      between trials eliciting faster and slower responses. The amplitudes of the N450,
      thought to reflect the suppression of a conceptual level processing system, and a
      temporo-parietal slow wave, thought to index the processing of color information,
      were greater when trials were mostly congruent in comparison to when trials were
      mostly incongruent. These findings indicate that the neural systems supporting
      inhibition and color processing are modulated by task demands. For the N450 the
      effect of task context interacted with the efficiency of attentional control
      being present for those trials eliciting faster responses and not for those
      trials eliciting slower responses. This finding is consistent with those from a
      growing number of studies indicating that the neural systems supporting
      attentional control are transient in nature, tending to fluctuate in efficiency
      over time.

PMID- 10915816
TI  - Ca(2+)-sensitive inhibition by Pb(2+) of alpha7-containing nicotinic
      acetylcholine receptors in hippocampal neurons.
AB  - In the present study the patch-clamp technique was applied to cultured
      hippocampal neurons to determine the kinetics as well as the agonist
      concentration- and Ca(2+)-dependence of Pb(2+)-induced inhibition of alpha7
      nicotinic receptors (nAChRs). Evidence is provided that more than two-thirds of
      the inhibition by Pb(2+) (3-30 microM) of alpha7 nAChR-mediated whole-cell
      currents (referred to as type IA currents) develops rapidly and is fully
      reversible upon washing. The estimated values for tau(onset) and tau(recovery)
      were 165 and 240 ms, respectively. The magnitude of the effect of Pb(2+) was the
      same regardless of whether acetylcholine or choline was the agonist. Pre-exposure
      of the neurons for 800 ms to Pb(2+) (30 microM) decreased the amplitude and
      accelerated the decay phase of currents evoked by moderate to high agonist
      concentrations. In contrast, only the amplitude of currents evoked by low agonist
      concentrations was reduced when the neurons were exposed simultaneously to Pb(2+)
      and the agonists. Taken together with the findings that Pb(2+) reduces the
      frequency of opening and the mean open time of alpha7 nAChR channels, these data
      suggest that Pb(2+) accelerates the rate of receptor desensitization. An
      additional reduction of type IA current amplitudes occurred after 2-min exposure
      of the neurons to Pb(2+). This effect was not reversible upon washing of the
      neurons and was most likely due to an intracellular action of Pb(2+). Pb(2+)
      induced inhibition of alpha7 nAChRs, which was hindered by the enhancement of
      extracellular Ca(2+) concentrations, may contribute to the neurotoxicity of the
      heavy metal.

PMID- 10915817
TI  - Selective blockade of muscarinic receptor subtypes in the brain stem reticular
      formation in rats: effects on anesthetic requirements.
AB  - Muscarinic involvement in the modulation of general anesthesia was examined in
      the rat with a cannula implanted in the pontine reticular formation. Atropine
      microinjected into the reticular formation reversed the minimum alveolar
      concentration (MAC) reducing effect of carbachol on halothane anesthesia, but
      M(1) or M(3) antagonist had no effect. An M(2) antagonist reduced the MAC of
      halothane following saline and carbachol. The results suggest that any of the
      muscarinic receptor subtypes in this region do not independently mediate the
      cholinomimetic effect on halothane anesthesia.

PMID- 10915818
TI  - Hexachlorophene-induced brain edema in rat observed by proton magnetic resonance.
AB  - Rat brain was examined with 4.7 T proton magnetic resonance (MR). On
      administering hexachlorophene (HCP) 30 mg/kg/day for 5 days, myelin-rich
      structures stood out in T2-weighted images. Apparent diffusion coefficient (ADC)
      was markedly suppressed in all regions examined except for cerebral cortex. Seven
      days after terminating the exposure to HCP, without enhancement in T2-weighted
      images, ADC was still decreased in corpus callosum, optic nerve and trigeminal
      nerve. Rat administered with HCP and followed with high magnetic field proton MR
      seems to provide a good model for cytotoxic brain edema, and it may also be
      useful to visualize heavily myelinated structures.

PMID- 10915819
TI  - Spatial encoding properties of subnucleus reticularis dorsalis neurons in the rat
      medulla.
AB  - The effect of spatial summation, produced by noxious thermal stimuli, was
      investigated on medullary Subnucleus Reticularis Dorsalis (SRD) neurons of
      anaesthetized rats. Neurons with 'whole body' receptive fields were excited by a
      random sequence of thermal stimuli involving four different surface areas of a
      hindpaw (1.9, 4.8, 7.5 and 18 cm(2)). The responses of SRD neurons progressively
      decrease when the area of noxious stimulation exceeded 4.8 cm(2). The shape of
      the stimulus-response curve closely match the shape of dorsal horn convergent
      neurons, previously recorded under similar experimental conditions. These results
      suggest that, with respect to spatial encoding properties, SRD neurons are driven
      by the same supraspinally-mediated inhibitory mechanisms as dorsal horn
      convergent neurons.

PMID- 10915820
TI  - Calretinin expression in the chick cochlear nucleus after deafferentation.
AB  - The expression of the calcium-binding protein calretinin (CR) in the chick
      cochlear nucleus, nucleus magnocellularis (NM), was examined after unilateral
      cochlea removal in hatchlings and 3-week-old birds. Following survival times of
      3, 6 or 12 h or 1, 3 or 7 days, CR mRNA was localized by in situ hybridization
      using a radiolabeled chick CR probe. Levels of CR protein were assessed by CR
      immunoreactivity (CR-I) using a calcium-independent CR antiserum and
      immunohistochemistry. At survival times of 1 day or less, cochlea removal did not
      change relative levels of CR mRNA or CR-I in NM between the deafferented and the
      unoperated sides of the brain. Decreases in CR expression on the cochlea removal
      side were observed, however, at times that coincide with deafferentation-induced
      cell loss (3 and 7 days). Additionally, bilateral cochlea removal had no apparent
      effect on CR-I in NM neurons when compared to those in normal animals. Thus, CR
      mRNA and protein appear to be constitutively expressed in NM neurons and are not
      affected by sensory deprivation.

PMID- 10915821
TI  - Suckling-induced increase in cyclic AMP exclusively in the central region of the
      rat adenohypophysis.
AB  - Investigating the cellular events in the pituitary gland, the intracellular
      cyclic AMP (cAMP) of the neural lobe (NL), intermediate lobe (IL), the inner (IZ
      AL) and outer zone (OZ-AL) of the anterior lobe (AL) have been measured during
      the suckling stimulus. Ten-minutes suckling, parallel to the elevation of plasma
      PRL, induced a significant increase of cAMP concentration in the IZ-AL. In
      contrast, 10- and 30-min suckling resulted in a decrease of cAMP level in the NL.
      Changes in cAMP of the OZ-AL and the IL as well as in the plasma level of alpha
      MSH could not be detected. These region-specific changes of cAMP in the pituitary
      gland during suckling stimulus seems to be related to interacting neuroendocrine
      signals delivered concomitantly from the hypothalamus and from the NIL to the IZ
      AL.

PMID- 10915822
TI  - Parasympathetic nerves influence cerebral blood flow during hypertension in rat.
AB  - This study tested the hypothesis that cerebral vasodilatation during marked acute
      hypertension is mediated in part through the influence of parasympathetic nerves
      from the pterygopalatine ganglia. Blood pressure was increased slowly in
      anesthetized rats after bilateral transection of the parasympathetic nerves.
      Cerebral blood flow was measured by laser flowmetry. Acutely hypertensive
      denervated animals developed significantly less cerebral vasodilatation than did
      control animals with intact nerves. Thus, parasympathetic vasodilator nerves
      contribute to vasodilatation seen with acute hypertension.

PMID- 10915823
TI  - Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx,
      45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells.
AB  - In cultured bovine adrenal chromaffin cells, NS-7 [4-(4-fluorophenyl)-2-methyl-6
      (5-piperidinopentyloxy) pyrimidine hydrochloride], a newly-synthesized
      neuroprotective drug, inhibited nicotine-induced 22Na(+) influx via nicotinic
      receptors (IC(50)=15.5 microM); the suppression by NS-7 was observed in the
      presence of ouabain, an inhibitor of Na(+),K(+)-ATPase, and was not attenuated
      upon the washout of NS-7. NS-7 decreased nicotine-induced maximum influx of
      22Na(+) without altering the EC(50) value of nicotine. Also, NS-7 diminished
      nicotine-induced 45Ca(2+) influx via nicotinic receptors and voltage-dependent
      Ca(2+) channels (IC(50)=14.1 microM) and catecholamine secretion (IC(50)=19.5
      microM). These results suggest that NS-7 produces noncompetitive and long-lasting
      inhibitory effects on neuronal nicotinic receptors in adrenal chromaffin cells,
      and interferes with the stimulus-secretion coupling.

PMID- 10915824
TI  - Noradrenergic neurons expressing substance P receptor (NK1) in the locus
      coeruleus complex: a double immunofluorescence study in the rat.
AB  - By using a double immunofluorescence method we examined the distribution of
      noradrenergic neurons expressing substance P receptor (NK1) or neuromedin K
      receptor (NK3) in the rat brainstem. The distribution of SPR-like immunoreactive
      (-LI) neurons completely overlapped that of tyrosine hydroxylase (TH)-LI neurons
      in the locus coeruleus (A6), ventrolateral and lateral reticular formation of
      pons (A5 and A7). Partially overlapping distribution of SPR- and TH-LI neurons
      were found in certain regions of the medulla oblongata (A1-A4). Neurons showing
      both SPR- and TH-like immunoreactivities, however, were only found in the locus
      coeruleus complex (A5-A7): 100% of these TH-LI neurons displayed SPR-like
      immunoreactivity. Neurons showing both NKR- and TH-like immunoreactivities were
      not detected in the aforementioned areas of brainstem. The present study has
      provided morphological evidence for direct physiological modulation of
      noradrenergic neurons by tachykinins through SPR in locus coeruleus complex (A5
      A7).

PMID- 10915825
TI  - Three novel neural pathways to the lacrimal glands of the cat: an investigation
      with cholera toxin B subunit as a retrograde tracer.
AB  - The distribution of ganglion neurons innervating the lacrimal gland (LG) was
      investigated following injection of cholera toxin B subunit into the LG of the
      cat. We report the first evidence that the otic ganglion (OG), and superior vagal
      and glossopharyngeal ganglia are also the sources of innervation of the LG. LG
      innervating neurons in the pterygopalatine ganglion and the OG could be divided
      into two subpopulations: small and large neurons. They may mediate the
      vasodilatation and secretion, respectively.

PMID- 10915826
TI  - Persistence of blood-to-brain transport of leptin in obese leptin-deficient and
      leptin receptor-deficient mice.
AB  - In lean CD-1 mice, leptin is delivered into the brain by a saturable transport
      mechanism. Previous work has shown that obesity is associated with decreased
      leptin transport. Here, we investigated the transport of leptin across the blood
      brain barrier (BBB) in two murine models of obesity. Radioiodinated leptin was
      intravenously injected into ob/ob (no leptin production) and db/db (high leptin
      levels, but no long-form leptin receptor) mutant mice and their lean controls. In
      all groups, the labeled polypeptide was transported across the BBB by a saturable
      mechanism. The rates of transport were not significantly different between the
      mutant strains and their lean controls. The results demonstrate that leptin
      transport persists in the absence of production of the endogenous polypeptide or
      its signal-transducing receptor and suggest that the impaired transport
      previously seen is not directly explained by only obesity or alterations in serum
      plasma levels.

PMID- 10915827
TI  - Depression of long term potentiation in gerbil hippocampus following postischemic
      hypothermia.
AB  - To investigate the mechanism of chronic cell death following postischemic
      hypothermia, the change of N-methyl-D-aspartate receptor (NMDAR) were examined by
      immunohistochemistry of NMDAR1 and long-term potentiation (LTP) in the CA1
      subfield of the gerbil hippocampus. At 1 week following postischemic hypothermia
      (32 degrees Cx4 h), all CA1 neurons survived; however, immunoreactivity of NMDAR1
      increased in neuronal perikarya whereas decreased in dendrites in the CA1
      neurons. The abnormality was still observed in remaining CA1 neurons at 1 month
      after hypothermia. LTP was also significantly depressed at 1 week after
      hypothermia. These results suggest that some abnormalities in the glutamate
      receptor may be caused by ischemia; such abnormality would persist in spite of
      hypothermia treatment, resulting in the depression of LTP.

PMID- 10915828
TI  - Kinetic and pharmacological properties of Ca(2+) currents in postganglionic
      sympathetic neurones projecting to muscular and cutaneous effectors.
AB  - Voltage-gated Ca(2+) channels are expressed in neurones and greatly influence
      neuronal activity by activating Ca(2+)-dependent K(+) channels. The whole cell
      patch-clamp technique was used to compare the kinetic and pharmacological
      properties of voltage-dependent Ca(2+) currents in two groups of sympathetic
      neurones identified by the fluorescent tracer Fast Blue: putative muscular
      sympathetic neurones (MSN) and putative cutaneous sympathetic neurones (CSN). The
      tracer was injected into the muscular part of the diaphragm (to mark MSN) and
      into the skin of the ear (to mark CSN). The capacitance of MSN (23.0 pF) was
      larger than the capacitance of CSN (12.6 pF). The maximum current in MSN (1.3 nA)
      was also larger than in CSN (0.93 nA). However, the current density was larger in
      CSN (77. 3 pA/pF) than in MSN (57.7 pA/pF) and the current activation rate was
      faster in CSN (0.27 nA/ms) than in MSN (0.19 nA/ms). V(1/2) and slope factors of
      activation and inactivation were not significantly different for MSN and CSN. The
      majority of Ca(2+) current was available for activation in both categories of
      neurones at resting membrane potential. Ca(2+) currents in MSN and CSN were
      blocked by nifedipine (7.0 and 3.6%, respectively), omega-Agatoxin-IVA (23.0 and
      25.6%, respectively) and omega-conotoxin-GVIA (67.0 and 65.1%, respectively). We
      found that CSN are twice as small, have higher Ca(2+) current density and their
      Ca(2+) activation rate is faster in comparison to MSN. Such properties may lead
      to faster rise of Ca(2+) concentration in the cytoplasm of the CSN comparing to
      MSN and more effectively dampen their activity due to more effective activation
      of Ca(2+)-dependent K(+) current. Both kinds of neurones express high proportion
      of N and P/Q Ca(2+) current.

PMID- 10915829
TI  - Orexin-induced hyperlocomotion and stereotypy are mediated by the dopaminergic
      system.
AB  - We demonstrated involvement of the ventral tegmental area (VTA) dopaminergic
      system in orexin-induced hyperlocomotion and stereotypy in rats. In double-label
      immunohistochemical study of rat brain, we found that tyrosine hydroxylase (TH)
      immunoreactive cells in the VTA received innervation from orexin immunoreactive
      fibers. Orexin-A induced an increase in [Ca(2+)](i) in isolated A10 dopamine
      neurons in a dose-dependent manner. In behavioral studies, we found that orexin-A
      induced hyperlocomotion, stereotypy and grooming behavior when administered
      centrally in rats, and these effects were abolished by dopamine D(2) (haloperidol
      and sulpiride) or D(1) (SCH23390) antagonists. These results suggest that the
      orexin-induced hyperlocomotion, stereotypy and grooming behavior are mediated by
      the dopaminergic system and this pathway might be involved in orexin-induced
      emotional responses.

PMID- 10915830
TI  - Block of rat brain recombinant SK channels by tricyclic antidepressants and
      related compounds.
AB  - SK channels are small conductance, Ca(2+)-activated K(+) channels that underlie
      neuronal slow afterhyperpolarization and mediate spike frequency adaptation.
      Using the patch clamp technique, we tested the effects of eight clinically
      relevant psychoactive compounds structurally related to the tricyclic
      antidepressants, on SK2 subtype channels cloned from rat brain and functionally
      expressed in the human embryonic kidney cell line, HEK293. Amitriptyline,
      carbamazepine, chlorpromazine, cyproheptadine, imipramine, tacrine and
      trifluperazine blocked SK2 channel currents with micromolar affinity. The block
      was reversible and concentration-dependent. The potency differed according to
      chemical structure. In contrast, the cognitive enhancer linopirdine was
      ineffective at blocking these channels. Our results point to a distinct
      pharmacological profile for SK channels.

PMID- 10915831
TI  - The putative <<silent>> 5-HT(1A) receptor antagonist, WAY 100635, has inverse
      agonist properties at cloned human 5-HT(1A) receptors.
AB  - Agonist binding to G protein-coupled receptors induces the formation of a
      receptor-G protein complex and subsequent guanosine 5'-diphosphate/guanosine 5'
      triphosphate (GDP/GTP) exchange. Some receptors, however, form receptor-G protein
      complexes and promote GDP/GTP exchange even when not occupied by agonists. Such
      receptors preferentially activate pertussis toxin-sensitive G proteins (i.e.,
      G(i)/G(o)), and the interactions of receptors and G proteins are affected by
      monovalent cations (most notably Na(+)), both in the occupied and unoccupied
      state. We investigated the effects of Na(+) on the intrinsic activity of 5
      hydroxytryptamine(1A) (5-HT(1A)) receptor ligands, measured as maximal effect
      (E(MAX)), using guanosine 5'-0-(3-[35S]thio)-triphosphate ([35S]GTPgammaS)
      binding to membranes prepared from human epithelioid carcinoma (HeLa) cells,
      expressing 500 fmol/mg protein of cloned human 5-HT(1A) receptor (HA7 cells). A
      decrease of the NaCl concentration decreased the maximal effect of serotonin,
      increased basal [35S]GTPgammaS binding, and increased the negative intrinsic
      activity of spiperone and N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]-N-(2
      pyridinyl)cyclohexaneca rboxamide (WAY 100635). This ability of WAY 100635 to
      decrease basal [35S]GTPgammaS binding was antagonized by (s)-N-tert-butyl-3-(4-(2
      methoxyphenyl)piperazine-1-yl)-2-phenylpropa namide ((s)-WAY 100135)
      (pA(2)=7.77). Further, WAY 100635 was able to antagonize carboxamidotryptamine (5
      CT)-stimulated [35S]GTPgammaS binding with a pA(2) of 9.9, in standard NaCl
      conditions, and of 9.7, in the absence of NaCl. Changes in membrane concentration
      did not affect the ability of WAY 100635 to decrease [35S]GTPgammaS binding. WAY
      100635 did not affect basal [35S]GTPgammaS binding to membranes from
      untransfected HeLa cells. Pertussis toxin (200 ng/ml) prevented WAY 100635 and
      spiperone to decrease [35S]GTPgammaS binding, showing that their effects were
      mediated by G proteins of the G(i)/G(o) family. In conclusion, the constitutive
      and stimulated activity of human 5-HT(1A) receptors expressed in HA7 cells is
      sodium-dependent, which allowed to confirm the 5-HT(1A) inverse agonist
      properties of spiperone, and to show that WAY 100635 is an inverse agonist at 5
      HT(1A) receptors that inhibits basal [35S]GTPgammaS binding to a lesser extent
      than spiperone. [35S]GTPgammaS binding to membranes from HA7 cells under low NaCl
      conditions appears to be especially suitable to evidence and pharmacologically
      analyze the inverse agonist properties of 5-HT(1A) receptor ligands.

PMID- 10915832
TI  - Mutational analysis and molecular modelling of the antagonist SR 144528 binding
      site on the human cannabinoid CB(2) receptor.
AB  - We have investigated the binding site of the subtype specific antagonist SR
      144528, (N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2. 1]heptan-2-yl]-5-(4-chloro-3
      methylphenyl)-1-(4-methoxybenzyl)- pyrazo le-3-carboxamide) on the human
      cannabinoid CB(2) receptor based on functional studies with mutated receptors.
      Two serine residues in the fourth transmembrane region, Ser(161) and Ser(165),
      were singly mutated to the cognate cannabinoid CB(1) receptor residue, alanine,
      and each gave receptors with wild-type properties for the cannabinoid agonists CP
      55,940 (1R,3R,4R)-3-[2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-4-(3
      hydroxypropyl)cyclohexan-1-ol) and WIN 55212-2 (R)-(+)[2, 3-dihydro-5-methyl-3
      [(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1, 4-benzoxazin-6-yl](1-naphthalenyl)
      methanone, which SR 144528 completely failed to antagonise. Molecular modelling
      studies show that SR 144528 interacts with residues in transmembrane domains 3,
      4, and 5 of the cannabinoid CB(2) receptor through a combination of hydrogen
      bonds and aromatic and hydrophobic interactions. In addition, the replacement by
      serine of a nearby cannabinoid CB(2) receptor-specific residue, Cys(175) resulted
      in wild-type receptor properties with CP 55,940, loss of SR 144528 binding and
      eight-fold reduced binding and activity of WIN 55212-2, a result compatible with
      a recently-proposed binding site model for WIN 55212-2.

PMID- 10915833
TI  - Mibefradil, an I(Ca,T) blocker, effectively blocks I(Ca,L) in rabbit sinus node
      cells.
AB  - To test the hypothesis that the Ca(2+) channel blocker mibefradil slows heart
      rate due to inhibition of T-type Ca(2+) current in pacemaker cells, we studied
      effects of mibefradil on action potentials and ionic currents of isolated rabbit
      sinus node cells using the patch clamp technique. Mibefradil (100 nM and 1
      microM) reduced spontaneous rate, decreased action potential amplitude and
      finally stopped impulse initiation. This action was not due to the drug effect on
      hyperpolarization-activated pacemaker current, but can be explained by
      attenuation of both T- and L-type Ca(2+) currents, which were inhibited by
      mibefradil almost equally (55% and 64% inhibition with 1 microM for T- and L
      types, respectively).

PMID- 10915834
TI  - Clonidine modulates BAY K 8644-induced rat behavior and neurotransmitter changes
      in the brain.
AB  - BAY K 8644 (methyl-1,4-dihydro-2, 6-dimethyl-3-nitro-4[2-trifluoromethyl-phenyl]
      pyridine-5-carboxylate), an activator of dihydropyridine-sensitive Ca(2+)
      channels, injected in rats [2 mg/kg intraperitoneally (i.p.)], induces behavioral
      changes including ataxia, increased sensitivity to auditory stimulation, stiff
      tail, arched back, limb tonus and clonus, and rolling over. Neurochemical changes
      in the brain 45 min after application of 2 mg/kg were characterized by a
      significant decrease of noradrenaline in the amygdala (-27.8%, P<0.02) and
      piriform cortex (-16.3%, P<0.02). No significant changes of catecholamines were
      found in the hippocampal subregions CA1, CA3 and dentate gyrus or in the septum
      as compared to controls. The dopamine metabolites, 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA), in the amygdala were elevated by 60%
      (P<0.02) and 66.7% (P<0.02), respectively. In the septum, a 52.6% (P<0.02)
      increase of HVA was observed. Analysis of amino acids revealed a marked increase
      of gamma-aminobutyric acid (GABA) content (+50.4%, P<0.001) in the septum.
      Pretreatment of the rats with the alpha(2)-adrenoceptor agonist, clonidine (0.1
      mg/kg i.p.), 30 min before BAY K 8644 (2 mg/kg i.p.) injection completely
      abolished the behavioral and neurochemical changes. The data suggest that the
      Ca(2+)-dependent neurotransmitter release provoked by BAY K 8644 can be modulated
      by stimulation of presynaptic alpha(2)-adrenoceptors. The effect of clonidine on
      the GABAergic system may represent an important mechanism involved in the
      prevention of BAY K 8644-induced behavior.

PMID- 10915835
TI  - Increased corticotropin-releasing factor concentrations in the bed nucleus of the
      stria terminalis of anhedonic rats.
AB  - Chronic mild stress in rats is an antidepressant-responsive model for anhedonic
      symptoms of major depression. Many patients with depression exhibit alterations
      in hypothalamic-pituitary-adrenal axis activity, and corticotropin-releasing
      factor (CRF) neuronal function. This study investigated the potential involvement
      of CRF and CRF receptors in the development of chronic mild stress-induced
      anhedonia in rats. Rats were subjected to 19 days of chronic mild stress, during
      which time anhedonia was periodically assessed by determining the threshold for
      self-stimulation of the ventral tegmental area. Anhedonic rats exhibited a 50%
      increase in CRF concentrations in the bed nucleus of the stria terminalis
      compared to control rats. There were no significant changes in hypothalamic
      pituitary-adrenal axis activity, CRF or CRF(1) receptor mRNA expression, or CRF
      receptor binding in the brain regions analyzed. Though preliminary, these results
      are consistent with the hypothesis that chronic stress-induced modulation of CRF
      function in specific brain structures such as the bed nucleus of the stria
      terminalis may contribute to the pathophysiology of depression.

PMID- 10915836
TI  - Evidence for an involvement of tachykinins in allodynia in streptozocin-induced
      diabetic rats.
AB  - A better knowledge of the pathophysiology of chronic pain could help to improve
      the treatment of patients with such syndrome. The aim of the present work was to
      elucidate the possible involvement of spinal substance P and neurokinin A in the
      mechanical and thermal allodynia observed in streptozocin-induced diabetic rats.
      A tachykinin NK(1) receptor antagonist, RP-67,580 ((3aR,7aR) -7, 7-diphenyl-2-(1
      imino-2(2-methoxy phenyl)-ethyl) perhydroisoindol-4-one hydrochloride), a
      tachykinin NK(2) receptor antagonist, SR-48,968 ((S)-N-methyl (4-(acetylamino
      4phenylpiperidino)-2-(3, 4-dichlorophenyl) butyl) benzamide) and their respective
      enantiomers were intrathecally administered 4 weeks after the induction of
      diabetes. Mechanical and thermal allodynia were evaluated before and up to 60 min
      after injection. The tachykinin receptor antagonists at the highest doses (10 and
      25 microgram) significantly reduced allodynia, their enantiomers being inactive.
      Both of these data suggest the involvement of substance P and neurokinin A in the
      neuropathy-induced allodynia and offer a novel hypothesis to treat chronic pain
      due to diabetes.

PMID- 10915837
TI  - Effects of a mu-opioid receptor agonist on G-protein activation in streptozotocin
      induced diabetic mice.
AB  - Many clinical and experimental studies have suggested that diabetes or
      hyperglycemia alter pain sensitivity, and sensitivity to several drugs. It has
      been reported that the antinociceptive potency of morphine is decreased in
      several rodent models of hyperglycemia, including streptozotocin-induced
      diabetes, an animal models of type I diabetes. The present study was designed to
      investigate in streptozotocin-induced diabetic mice the effect of the selective
      micro-opioid agonist [D-Ala(2), NMePhe(4), Gly-ol(5)]enkephalin (DAMGO) on G
      protein activation by monitoring guanosine-5'-O-(3-[35S]thio)triphosphate
      ([35S]GTPgammaS) binding to pons/medulla membranes, which contain the key areas
      for opioid antinociception. In the tail-flick test, DAMGO (1-10 ng,
      intracerebroventricularly) produced a marked dose-dependent antinociception in
      non-diabetic mice. In streptozotocin-induced diabetic mice, the effect of DAMGO
      was significantly attenuated as compared to that in non-diabetic mice. In the
      [35S]GTPgammaS binding assay, DAMGO (0.1-10 microM) increased the binding of
      [35S]GTPgammaS to pons/medulla membranes from non-diabetic mice in a
      concentration-dependent manner, affording approximately 100% maximal stimulation
      at 10 microM. The maximal stimulation of [35S]GTPgammaS binding by DAMGO (10
      microM) in streptozotocin-induced diabetic mice (100.55+/-3.12%), was similar to
      non-diabetic mice. The present results indicated that the antinociceptive effect
      of DAMGO given supraspinally was less potent in streptozotocin-induced diabetic
      mice than that in non-diabetic mice, whereas the mu-opioid receptor-mediated G
      protein activation in pons/medulla was unaltered in streptozotocin-induced
      diabetic mice. Thus, the attenuation of DAMGO-induced antinociception in
      streptozotocin-induced diabetic mice is probably caused by dysfunction in
      cellular pathways after the activation of G-proteins.

PMID- 10915838
TI  - Purinergic and noradrenergic cotransmission in the rat pineal gland.
AB  - ATP is coreleased with noradrenaline in several noradrenergic synapses, and P2
      like receptors were shown to be present in rat pineal glands. A new method of
      functional investigation was developed to assess the importance of both
      transmitters (noradrenaline and ATP) in eliciting the synthesis of melatonin and
      its precursor N'-acetyl-5-hydroxytryptamine (N'-acetyl-5-HT) through transmural
      electrical field stimulation of cultured pineal glands. Incubation with the beta
      adrenoceptor antagonist propranolol (>10(-7) M) blocked almost completely the
      production of N'-acetyl-5-HT, whilst the P2 receptor antagonists
      pyridoxalphosphate-6 azophenyl-2',4'-disulfonic acid (PPADS, >3x10(-6) M) and
      suramin (>10(-6) M) blocked it partially. These findings indicate a
      physiologically relevant role for the purinergic cotransmission in this system.

PMID- 10915839
TI  - SCH 58261 and ZM 241385 differentially prevent the motor effects of CGS 21680 in
      mice: evidence for a functional 'atypical' adenosine A(2A) receptor.
AB  - The acute motor effects elicited by drugs acting upon adenosine A(2A) receptors,
      namely the highly selective agonist CGS 21680 or the antagonists SCH 58261 and ZM
      241385, were investigated in mice. CGS 21680 dose-dependently (0.1-2.5 mg/kg
      i.p.) decreased horizontal and vertical motor activities. The depressant effect
      of CGS 21680 (0. 5 mg/kg i.p.) was maintained in mice pretreated by the adenosine
      receptor antagonist 8-(p-sulfophenyl)-theophylline (10-30 mg/kg i.p. ), which
      poorly penetrates the blood-brain barrier, but was completely lost in adenosine
      A(2A) receptor knockout mice. Thus, the adenosine A(2A) receptor is critically
      involved in motor activity. SCH 58261 (1-10 mg/kg i.p.) increased locomotion and
      rearing with a quick onset, but for a shorter period in mice habituated to the
      environment than in mice unfamiliar to it. ZM 241385 (7.5-60 mg/kg i. p.)
      stimulated horizontal and vertical activities with a slow onset at the two
      highest tested doses, similarly in naive and in habituated mice. The increase in
      locomotion elicited by ZM 241385 (15-30 mg/kg i.p. and 10-20 nM i.c.v.) was
      retained in mice treated by CGS 21680 (0.5 mg/kg i.p.) but that elicited by SCH
      58261 (1-3-10 mg/kg i.p. and 10-20 nM i.c.v.) partially subsided. In conclusion,
      both 'striatal-like'/'SCH 58261-sensitive' adenosine A(2A) receptors and 'ZM
      241385-sensitive'/'atypical' CGS 21680 binding sites may mediate CGS 21680
      induced motor effects. Moreover, our results suggest that 'atypical' CGS 21680
      binding sites could be adenosine A(2A) receptors with a peculiar pharmacological
      profile.

PMID- 10915840
TI  - Effects of a seven-day continuous infusion of L-DOPA on daily rhythms in the rat.
AB  - The present study was conducted to evaluate the effect of L-3, 4
      dihydroxyphenylalanine (L-DOPA) on the daily rhythms of temperature, heart rate
      and locomotor activity in rats that received a 7-day continuous infusion. Our
      results indicate that L-DOPA does not induce a loss of the daily rhythmicity of
      temperature, heart rate and locomotor activity but modifies the main parameters
      of these rhythms, e.g. it increased the MESOR (midline estimating statistic of
      rhythm) of temperature and heart rate and increased the amplitude of temperature
      but decreased the amplitude of heart rate. Taking into account these results
      obtained after constant rate delivery, we now plan to investigate the effects of
      DOPA therapy by changing the time of its administration.

PMID- 10915841
TI  - Interaction of cyclic AMP modulating agents with levcromakalim in the relaxation
      of rat isolated mesenteric artery.
AB  - The effect of cyclic AMP modulating agents on levcromakalim-induced relaxation
      was investigated in myograph-mounted rat mesenteric arteries. Forskolin (adenylyl
      cyclase activator), dibutyryl cyclic AMP (protein kinase A activator) and 5'-N
      ethylcarboxamidoadenosine (NECA; adenosine receptor agonist) all potentiated the
      vasorelaxant effects of levcromakalim. The modulatory and relaxant effects of
      dibutyryl cyclic AMP, NECA and forskolin were sensitive to the protein kinase A
      inhibitor, Rp-cAMPS. However, relaxation to these three agents was unaffected by
      the K(ATP) inhibitor, glibenclamide. Dibutyryl cyclic AMP and NECA also caused
      levcromakalim to induce relaxation in the sub-nanomolar concentration range,
      however, this effect was Rp-cAMPS- and glibenclamide-insensitive. These results
      suggest that cyclic AMP modulating agents modulate K(ATP), even though this
      channel does not contribute to their relaxant effects.

PMID- 10915842
TI  - The effect of SK-896 on post-operative ileus in dogs: gastrointestinal motility
      pattern and transit.
AB  - The aim of this study was to investigate the effect of SK-896 (Phe-Val-Pro-Ile
      Phe-Thr-Try-Gly-Glu-Leu-Gln-Arg-Leu-Gln-Glu-Lys-Glu- Arg-Asn-Lys-Gly-Gln-Hse), a
      new motilin analogue, on gastrointestinal motility and transit in dogs with post
      operative ileus, and to compare the effects of this agent on these parameters
      with the effects of prostaglandin F(2alpha), a well-known gastroprokinetic agent.
      We used chronically implanted force transducers to measure motility and
      radiography of radio-opaque markers to measure transit. Infusion of SK-896 1
      microgram/kg/h, for 20 min twice a day induced interdigestive migrating
      contractions-like motility. Infusion of prostaglandin F(2alpha), 20
      microgram/kg/h, for 1 h twice a day induced continuous contractions in the distal
      part of the small intestine. The time of first appearance of interdigestive
      migrating contractions in the stomach (gastric-interdigestive migrating
      contractions) and the gastric emptying time of the solid marker with the
      administration of SK-896 were significantly less than those noted with the
      administration of prostaglandin F(2alpha). It appears that gastric-interdigestive
      migrating contractions play an important role in the transit of substances,
      especially solid substances, in the gastrointestinal tract. We conclude that SK
      896, which induced gastric-interdigestive migrating contractions, is effective to
      induce early recovery from post-operative ileus.

PMID- 10915843
TI  - Reduced inflammation in genetically hypertensive rat airways is associated with
      reduced tachykinin NK(1) receptor numbers.
AB  - The airways of the genetically hypertensive rat (GH) are hyperinnervated by
      substance P-containing sensory nerves and exhibit reduced inflammatory
      responsiveness to substance P and to capsaicin. The present study measured
      tracheal inflammation to resiniferatoxin (1.0 microgram/kg i.v.), a capsaicin
      analogue, which lacks the hypotensive action of capsaicin itself, alone or after
      the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole
      (TRIM) (50 mg/kg i.p.). The inflammatory response to resiniferatoxin alone was
      50% lower in untreated GH than in control rats, a similar strain difference to
      that seen previously with capsaicin. Pre-treatment with TRIM had no effect on
      inflammation in either strain. Binding kinetics of the tachykinin NK(1) receptor
      antagonist [3H](S)-1-(2-[3-(3, 4-dichlorophenyl)-1-(3
      isopropoxyphenylacetyl)piperidin-3-yl]ethyl)-4- phenyl-l
      azoniabicyclo[2,2,2,]octane chloride ([3H]SR140333)(0.125-16.0 nM) showed 50%
      reduction of B(max) in GH versus control tracheae (74+/-13 cf.165+/-26 fmol/mg
      protein). Our results indicate that the reduced neurogenic inflammatory
      responsiveness in GH rats can be attributed entirely to reduced tachykinin NK(1)
      receptor numbers.

PMID- 10915844
TI  - Polyreactivity as an acquired artefact, rather than a physiologic property, of
      antibodies: evidence that monoreactive antibodies may gain the ability to bind to
      multiple antigens after exposure to low pH.
AB  - Evidence is presented that monoreactive antibodies exposed to low pH may acquire
      the ability to bind to multiple antigens. M11, a murine, monoclonal, IgM(K) anti
      goat IgG (GIgG) was purified from a hybridoma supernatant by elution at low pH
      from an anti-mu-Sepharose 4B affinity column. By measuring the specific antiGIgG
      activities and the affinity constants for the interactions of M11, pre- and post
      affinity-purification, with GIgG, M11 was shown to be monoreactive before
      purification. Quite unexpectedly, however, the affinity-purified M11 reacted
      extensively with size-fractionated liver proteins when tested in an immunoblot,
      clearly indicating that it was polyreactive. It was concluded that the exposure
      to low pH had altered the M11 binding-site so as to allow it to bind to many
      different proteins. This phenomena provides an alternative basis for interpreting
      the polyreactivity observed following affinity-purification.

PMID- 10915845
TI  - Flow cytometric discrimination between viable neutrophils, apoptotic neutrophils
      and eosinophils by double labelling of permeabilized blood granulocytes.
AB  - Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) is
      frequently used to detect apoptotic cells in tissues, cytospins and suspensions.
      Here we show that TUNEL staining of freshly isolated granulocytes results in non
      specific positivity of a distinct population, which can be observed in the
      presence or absence of TdT. The morphological features of the false-positive
      cells examined in fluorescence microscopy suggest that the non-specifically
      stained cells are eosinophilic granulocytes. Granules of eosinophilic
      granulocytes were brightly stained by non-specific TUNEL reaction independent of
      TdT. This staining does not, therefore, indicate apoptosis and most likely
      reflects 'stickiness' of the permeabilized eosinophils. Immunofluorescence with
      phycoerythrin (PE)-labelled CD16 antibodies performed simultaneously with
      conventional TUNEL staining confirmed that the false-positive cells in TUNEL
      staining were CD16-negative eosinophils. In this report we describe a new
      procedure that allows: (i) the differentiation of neutrophilic and eosinophilic
      granulocytes in forward scatter versus log side scatter histograms after
      permeabilisation; (ii) the reliable discrimination between viable neutrophils,
      apoptotic neutrophils and eosinophilic granulocytes in cytofluorimetry.

PMID- 10915846
TI  - Detection of caspase-activation in intact lymphoid cells using standard caspase
      substrates and inhibitors.
AB  - Members of the caspase family of proteases are important in the implementation of
      apoptotic cell death. These caspases are intracellularly activated upon a death
      stimulus, and exhibit a distinctive proteolytic activity which transmits a death
      signal and readily detected by measuring the cleavage of synthetic substrates in
      cell extracts. In this report, we show that apoptosis-associated caspase
      activation can be recorded not only in cell lysates but also in intact lymphoid
      cells with commercially available peptides which are either biotinylated or carry
      an amino-methylcoumarin (AMC) group. Incubation of intact cells induced to
      undergo apoptosis with Ac-Asp-Glu-Val-Asp-AMC (DEVD-AMC) leads to the release of
      AMC in amounts very similar to the amounts released when cell extracts are
      prepared and incubated with DEVD-AMC. This release can be detected by a
      fluorescence read-out and is blocked by caspase-inhibitors such as Ac-DEVD-cho or
      Z-VAD-fmk. Similarly, labelling of intact cells with the biotinylated peptides
      Tyr-Val-Ala-Asp-cmk (YVAD-cmk) or YVAD-faom permits the detection of active
      caspases by affinity blotting and the detection of apoptotic cells by FACS
      analysis. These methods enable the investigator to detect at the single-cell
      level those cells which have activated their caspases and to evaluate such
      activation without the need for lysis of the cells.

PMID- 10915847
TI  - Detection of structural gene mutations and promoter polymorphisms in the mannan
      binding lectin (MBL) gene by polymerase chain reaction with sequence-specific
      primers.
AB  - This study describes a new approach to the determination of all known mannan
      binding lectin (MBL) mutations. The distribution of known variants of the MBL
      gene in a population of healthy unrelated Danes was determined and the genotype
      was correlated with the plasma MBL concentrations. The following genetic
      polymorphisms were studied: three point mutations in the promoter region at
      position -550 (H/L variants), -221 (X/Y variants), -70 (nt C or T), one point
      mutation in the 5' untranslated (UT) region at position +4 (P/Q variants) and
      three point mutations located at codons 52, 54 and 57 in exon 1 of the MBL gene,
      at nucleotide positions 223, 230 and 239, respectively. To perform genotyping, we
      designed sequence specific primers for a polymerase chain reaction (PCR-SSP). PCR
      SSP is a powerful technique for the discrimination of alleles resulting from
      single base substitutions and is a widely used technique. Another major advantage
      of the PCR-SSP method is its ability to determine whether sequence motifs are in
      cis or trans. The frequencies of variants in exon 1 obtained by PCR-SSP were
      completely comparable to results obtained by previously described PCR methods,
      restriction fragment length polymorphism (RFLP) and site-directed mutagenesis
      (SDM). This PCR-SSP method is performed with standard laboratory equipment and
      has the capacity to detect all genetic variants in 100 samples in 2 days at an
      estimated total cost of GBP 11 per sample. Analysing the correlation between MBL
      haplotype and plasma MBL levels, we confirmed that three different structural
      variants, B, C and D and the promoter haplotypes HY, LY and LX have a dominant
      effect on the concentration of MBL. The HY haplotype is associated with the
      highest plasma concentration, the LY haplotype with intermediate levels and the
      LX haplotype with the lowest levels. The LX haplotype was found to be associated
      with very low levels of MBL similar to those found in association with the
      structural B genotype. The gene frequencies of variants in the MBL gene in the
      Danish population studied correspond to previous reports on Caucasian
      populations.

PMID- 10915849
TI  - IFNgamma secretion following stimulation with total tumor peptides from
      autologous human tumors.
AB  - Several issues remain to be resolved before the efficacy of various approaches to
      elicit anti-tumor immunity in patients can be evaluated. First, in vitro assays
      able to detect responses by T cells primed in vivo are needed. Second, a source
      of tumor antigen to stimulate patients' lymphocytes in vitro is required. The
      ELISPOT assay is attractive, because it can be performed with a small numbers of
      cells and requires only short-term culture in vitro. A source of tumor antigen is
      more problematic, since for most tumors, tumor-associated antigens (TAA) have not
      been identified and/or cloned. In this report we demonstrate that autologous
      antigen-presenting cells (APC) pulsed with total tumor peptides from autologous
      tumor tissue can stimulate IFNgamma release by patients' lymphocytes in the
      ELISPOT assay. Thus, this approach should be considered for monitoring immune
      responses in clinical immunotherapy trials.

PMID- 10915848
TI  - Monoclonal antibodies against the human interleukin-11 receptor alpha-chain (IL
      11Ralpha) and their use in studies of human mononuclear cells.
AB  - A panel of 14 hybridoma cell lines secreting monoclonal antibodies against the
      human interleukin-11 receptor alpha chain (hIL-11Ralpha) was obtained using two
      different approaches. Two antibodies were raised against peptides of the N- and C
      terminal sequences, respectively, of the extracellular part of the hIL-11Ralpha.
      Another group of 12 antibodies was generated against a hybrid protein consisting
      of the extracellular part of the hIL-11Ralpha fused to mature full-length human
      IL-2. All these antibodies recognized native hIL-11Ralpha and most also
      recognized the denatured receptor on immunoblots after SDS-PAGE. Four different
      epitopes were identified on the extracellular part of the hIL-11Ralpha. One
      epitope, defined by the E27 antibody, is located at the N-terminus and the other
      three epitopes are clustered in the membrane-proximal, C-terminal region. The
      antibodies defining epitopes I and II recognized membrane-bound hIL-11Ralpha
      expressed in gp130/hIL-11Ralpha-co-transfected Ba/F3 cells. The E27 antibody
      cross-reacted with murine IL-11Ralpha, in agreement with the fact that the N
      terminal region is highly conserved between species. The other 13 antibodies all
      recognized a region between amino acids 319 and 363, which is the membrane
      proximal part of the hIL-11Ralpha. This region, which is less conserved between
      mouse and human, is shown here to be an immunodominant region. Anti-IL-11Ralpha
      monoclonal antibodies, which have not been described previously enabled us to
      explore the expression and tissue distribution of IL-11Ralpha on human peripheral
      blood mononuclear cells and cell lines. The antibodies provide powerful tools for
      the study of the regulation and function of the receptor.

PMID- 10915850
TI  - Adenoviral transduction of human 'clinical grade' immature dendritic cells
      enhances costimulatory molecule expression and T-cell stimulatory capacity.
AB  - The therapeutic use of dendritic cells (DC) in antigen-specific anti-tumor
      vaccines, requires sufficient numbers of functional DC, the preparation of which
      should comply with the code of Good Manufacturing Practice. In addition, the
      expression of tumor specific antigen should be possible in these DC. As a
      preclinical step, the method reported here was developed in healthy volunteers.
      Monocytes (Mo) were isolated by leukapheresis from 12 donors, purified by
      elutriation and then cultured for 6 days in sealed bags in AIM-V serum free
      medium with granulocyte-macrophage colony-stimulating factor (GM-CSF) and
      interleukin-13 (IL-13). Between 6x10(8) and 1x10(9) immature DC (iDC) could be
      differentiated from one leukapheresis. Cells displayed a characteristic iDC
      phenotype (CD1a(+), CD14(-), CD80(+), CD86(+), HLA DR(+), CD83(-)), and had
      potent allogeneic and antigen dependent autologous T cell-stimulatory capacity.
      Moreover, iDC could be further differentiated into mature DC by CD40 ligation as
      assessed by CD83 expression and the upregulation of HLA-DR and costimulatory
      molecules. After infection with a recombinant adenovirus encoding for beta
      galactosidase (betaGal), 50% to 80% of iDC expressed betaGal without toxicity.
      Adenovirus infection increased the expression of both costimulatory molecules and
      CD83, and also increased allogeneic stimulatory capacity. Thus, the method
      developed here allows us to use large numbers of functional iDC as will be
      required for therapeutic uses in man. These DC can express a transgenic protein.

PMID- 10915851
TI  - Synthetic peptides as putative therapeutic agents in transplantation medicine:
      application of PEPSCAN to the identification of functional sequences in the
      extracellular domain of the interleukin-2 receptor beta chain (IL-2Rbeta).
AB  - A desired treatment strategy in transplantation medicine is the selective
      targeting of alloreactive T cells without impairing antileukemic and antiviral
      activities. One approach is the synthesis of peptides that interfere with the
      binding of interleukin-2 (IL-2) to its high affinity receptor (IL-2R). This
      blocks the activation and proliferation of the antigen-activated T cells and the
      secretion of IL-2. The latter binds to its receptor, via the extracellular domain
      of the IL-2Rbeta chain, while its cytoplasmic domain is required for
      intracellular signal transduction. In this study, the PEPSCAN method was applied
      in order to identify antigenic sequences (epitopes) in the extracellular domain
      of the IL-2Rbeta. Based on the primary amino acid (aa) sequence of the IL-2Rbeta,
      a total of 239 overlapping dodecapeptides, spanning the entire sequence of IL
      2Rbeta, were synthesized by PEPSCAN and their immunoreactivity was tested by
      ELISA using monoclonal antibodies (mAbs) specific for IL-2Rbeta such as TU11,
      Mikbeta1, HuMikbeta1 and TU27. TU11 recognized a linear epitope located in the
      region 85R-Q(96). None of the 239 synthetic peptides was recognized by TU27.
      Mikbeta1 (and HuMikbeta1) recognized a discontinuous epitope formed by aa located
      in the IL-2Rbeta domains L(106) to P(148) and E(170) to A(202). Subsequently,
      synthetic peptides corresponding to the identified putative epitopic sequences
      were prepared by solid phase synthesis and their immunogenicity in vivo was
      assessed by raising polyclonal antibodies. Given that Mikbeta1 and HuMikbeta1
      inhibit binding of IL-2 on the IL-2Rbeta, we addressed the question of whether
      the identified antigenic sequences serve as putative IL-2 binding domains.
      Synthetic peptides corresponding to these sequences were tested for their ability
      to compete with IL-2 for binding and, thereby, inhibit IL-2-induced proliferation
      of mitogen-stimulated human peripheral blood T cells. Sequences 107M-E(118) and
      178Y-Q(199) probably represent functional IL-2 binding domains on IL-2Rbeta,
      since these synthetic peptides significantly inhibited the proliferation of
      activated T cells and secretion of IL-2.

PMID- 10915852
TI  - Dependence of T cell activation on area of contact and density of a ligand-coated
      surface.
AB  - An apparatus which allows precise control of the time of initiation and the area
      of contact of cells with immobilized ligands has been developed. Cells are
      trapped in an asymmetric film that can be quantitatively thinned, forcing the
      cells into close contact with ligands adsorbed on the base of the apparatus.
      Using microbeads to indicate the film height, the amount of thinning can be
      controlled to within 1 microm, producing known contact areas between cells and
      the ligand-coated surface. This system was used with anti-CD3-coated surfaces of
      different densities to examine the effect of ligand density on T cell activation,
      while keeping the number of ligands presented to the cells constant. T cell
      activation was observed individually in each cell as intracellular calcium
      mobilization. In these experiments both the percent of T cell activation and the
      rate of calcium rise were found to depend only on the number of anti-CD3
      molecules presented and not on their density. This implies that the spacing
      between molecules is not important in the range studied, and suggests that
      receptor clustering to levels higher than dimers may not be necessary for
      induction of calcium mobilization by anti-CD3.

PMID- 10915853
TI  - Semi-quantification of human C-C chemokine mRNAs with reverse transcription/real
      time PCR using multi-specific standards.
AB  - A reverse transcription/real-time polymerase chain reaction (PCR) assay was
      established to semi-quantify the mRNA levels of the human C-C chemokines RANTES,
      MIP-1beta and MCP-1 relative to the housekeeping gene beta-actin. The assay
      showed a high sensitivity (below 60 cDNA molecules/10 microl reaction) and
      dynamic range (8 log units); both within-assay and inter-assay variability were
      below 0.06 log units and the accuracy was +/-0.06 log units for all four
      chemokines. Moreover, it is demonstrated that a multi-specific DNA fragment,
      which had previously been constructed for competitive PCR, can be used as a
      reliable external standard. This allows a direct semi-quantitative comparison of
      different chemokine mRNA levels and is a convenient alternative to the use of
      different sets of homologous external standards. The method was successfully
      applied to the semi-quantification of chemokines in human liver specimens and
      should be useful in further studies on steady state mRNA levels of C-C chemokines
      from low cell numbers or small tissue specimens.

PMID- 10915854
TI  - Discrimination between NK and LAK cytotoxic activities of murine spleen cells by
      MTT assay: differential inhibition by PGE(2) and EDTA.
AB  - In the present study we propose a mathematical approach to improve the analysis
      of NK and LAK activities measured by MTT assay adapted for murine cells. We found
      that to calculate NK activity, high E:T ratios should be used (up to 50:1) and
      the phenomenon fits to a linear least-squares analysis. However, 5-fold less
      effector cells (10:1, E:T) should be used to detect LAK activity and the
      phenomenon has a nonlinear exponential behavior. Using this approach, we showed
      that EDTA inhibits LAK but not NK activity whereas PGE(2) inhibits NK but not LAK
      activity. In conclusion, this analytical approach allowed the discrimination
      between NK and LAK activities and exposed differences between these two cytotoxic
      activities.

PMID- 10915855
TI  - Staining of antigen activated lymphocytes (SAAL): a highly specific method for
      flow cytometric quantitation of tumor-specific CD8(+) T cells.
AB  - A novel method for quantitative analysis of tumor-specific CD8(+) T lymphocytes
      was developed. Lymphocytes from mice vaccinated with tumor-associated antigens
      (TAAs) were expanded for 5 days in tissue culture and then stimulated in vitro
      for 5 h with tumor cells. They were subsequently surface-stained for CD8 and for
      intracellular interferon gamma (IFN-gamma) and analyzed by flow cytometry. The
      specificity and sensitivity of this assay, staining of antigen-activated
      lymphocytes (SAAL), was comparable to that of surface staining with major
      histocompatibily class (MHC) I-peptide tetramers or of staining of peptide re
      stimulated CD8(+) T cells for intracellular IFN-gamma. The assay did not exhibit
      the high background activity of traditional 51Cr-release assays that without
      elaborate effector cell purifications commonly fail to distinguish between T cell
      mediated antigen-specific cytolysis and non-specific lysis by lymphokine
      activated killer (LAK) cells. The described method, which does not require prior
      identification of individual TAAs and their T cell epitopes nor access to
      specific reagents such as MHC-peptide tetramers, represents a simple yet useful
      technique for studying tumor-specific cytolytic T cell responses.

PMID- 10915856
TI  - Quantification of DNA binding to cell-surfaces by flow cytometry.
AB  - DNA binding to cell-surfaces has been documented in several studies. The
      interaction of DNA with cells has been shown to have therapeutic potential as a
      non-viral form of gene delivery and DNA vaccination. Recently, bacterial DNA
      binding and internalization has been demonstrated in some cells to trigger
      secretion of cytokines and cell activation. Previous studies to quantify DNA
      binding to cells have used radiolabeled DNA. Here we report a non-radioactive
      assay for quantification of cell-surface DNA binding based on the isoparametric
      analysis of flow cytometric data as described by Chatelier et al., Embo J., 5
      (1986) 1181. This assay has the advantage over previously used procedures in not
      employing radioactive material and being able to discriminate viable from non
      viable cells that bind DNA. With the importance of understanding the interaction
      of DNA with cells, this assay may have application for the identification and
      characterization of reagents designed to either enhance or inhibit DNA binding to
      cells.

PMID- 10915857
TI  - Phage display of peptide/major histocompatibility complex.
AB  - To date, there is no direct way to determine the antigenic specificity of T
      cells. While B-cell epitopes can be selected from phage-displayed libraries of
      peptides, the corresponding molecular tool for identifying T-cell epitopes does
      not yet exist. The natural ligands of the T-cell antigen-receptor (TCR) are
      essentially antigenic peptides (P) associated with the products of the major
      histocompatibility complex (MHC). Here, we report phages displaying P-MHC
      complexes. Single-chain P-MHC class I molecules, produced in E. coli periplasm,
      stimulate T-cells in a peptide-specific fashion. The same P-MHC, fused at the tip
      of filamentous phage, directed their binding to a recombinant TCR restricted to
      the displayed MHC haplotype (H-2K(d)). Importantly, the binding of P-K(d)-fd to a
      K(d)-restricted TCR, and also to K(d)-restricted T-cell hybridomas, was modulated
      by the displayed peptide. Therefore, we suggest phage display of P-MHC as a
      direct molecular tool for probing T-cell specificity, and for selecting TCR
      ligands from genetic libraries encoding randomized or natural peptides.

PMID- 10915858
TI  - Cell-growth control by monomeric antigen: the cell surface expression of lysozyme
      specific Ig V-domains fused to truncated Epo receptor.
AB  - Previously we have shown that the V(H) and V(L) fragments of an anti-hen egg
      lysozyme (HEL) antibody HyHEL-10 are weakly associated but can be driven together
      by antigen. By joining these antibody variable domains to the cytoplasmic portion
      of the murine erythropoietin receptor, we created a chimeric growth factor
      receptor that could be activated by HEL. After co-transfection with two plasmids
      encoding the respective chimeric receptors in IL-3 dependent murine pro-B Ba/F3
      cells, a portion of the cells survived under antigen dependent stimulation
      without IL-3. These surviving cells all showed coexpression of the two chimeric
      receptor chains and demonstrated HEL dose-dependent growth stimulation without IL
      3. When another IL-3 dependent cell line 32D was transfected with a variant of
      such chimeric receptor with a linker peptide (Gly-Ser-Gly) inserted between
      V(H)/V(L) and EpoR domains, an improved growth response was attained. These
      observations suggest the utility of heterodimeric Fv chimeric receptors in
      creating cells that respond to monomeric antigen.

PMID- 10915859
TI  - Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided
      selection.
AB  - With the advent of phage display antibody libraries, humanization of murine
      antibodies can be achieved by epitope guided selection. In present study, guided
      selection was applied to the humanization of the mouse mAb Z8 that is directed to
      human TNF-alpha and can neutralize the cytotoxicity of TNF-alpha. First, the Z8
      Fd gene was paired as a template with a repertoire of human kappa chains, and
      displayed on the filamentous phage, forming a hybrid phage antibody library.
      Selected by four rounds of panning against TNF-alpha, hybrid antibody fragments
      that bound to TNF-alpha and contained human kappa chains were obtained. Meanwhile
      human Fd genes were selected by pairing the human Fd repertoire with the Z8 kappa
      chain and performing the same procedure of panning. One of the isolated human Fd
      genes (huFd2), which showed the strongest reactivity, was chosen to pair with 12
      of selected human kappa chains. Two of the resulting human Fabs (huFd2-hukappa1
      and huFd2-hukappa2), with same Fd and different kappa chains, bound to TNF-alpha
      specifically. Their human origin was proved by ELISA and sequencing analysis. The
      human Fabs competitive ELISA and in vitro TNF-alpha neutralization assay
      demonstrated that the human Fabs resembled its parental mouse mAb Z8 in that they
      both recognized the same epitope and neutralized the cytotoxicity of TNF-alpha.
      These results suggest that guided selection is a promising strategy in murine mAb
      humanization.

PMID- 10915860
TI  - Isolation and purification of lymphocyte subsets from gut-associated lymphoid
      tissue in neonatal swine.
AB  - The characterization of lymphoid subsets isolated from different anatomical sites
      is of great importance for understanding the mechanisms and interactions of
      normal and pathological immune reactions in the pig. The objective of this study
      was to standardize a protocol for the isolation of lymphocytes from mucosal
      tissues of neonatal pigs. Specific protocols for the isolation of lymphocytes
      from Peyer's patches of jejunum (jejPP) and ileum (ilPP), the Intraepithelial
      (IE) and lamina propria (LP) compartments of the jejunum and ileum, the
      mesenteric lymph nodes (MLN), and the peripheral blood (PBMC) are described in
      detail. The analysis of the cells isolated indicated a high viability (>90%). The
      histological sections from fragments collected from the intestine demonstrated
      that in nursing young pigs, the recovery of IE and LP lymphocytes may be limited
      because of the low numbers of lymphocytes present in early age. In addition, the
      presence of large intracytoplasmic vacuoles and hyaline droplets between the
      columnar epithelial cells during the first week of age interferes with the
      isolation of pure lymphocytes from the IE and LP compartments. Optimal lymphocyte
      yields for all the samples analyzed was confirmed by immunostaining with the pan
      lymphocyte marker, CD45. The successful isolation and comparison of large numbers
      of pure populations from compartmentalized areas of the intestine and associated
      lymphoid tissues opens up a broad area for the investigation of mucosal immune
      responses of pigs.

PMID- 10915861
TI  - Yeast as an honorary mammal.

PMID- 10915862
TI  - Nucleotide excision repair in yeast.
AB  - In nucleotide excision repair (NER) in eukaryotes, DNA is incised on both sides
      of the lesion, resulting in the removal of a fragment approximately 25-30
      nucleotides long. This is followed by repair synthesis and ligation. The proteins
      encoded by the various yeast NER genes have been purified, and the incision
      reaction reconstituted in vitro. This reaction requires the damage binding
      factors Rad14, RPA, and the Rad4-Rad23 complex, the transcription factor TFIIH
      which contains the two DNA helicases Rad3 and Rad25, essential for creating a
      bubble structure, and the two endonucleases, the Rad1-Rad10 complex and Rad2,
      which incise the damaged DNA strand on the 5'- and 3'-side of the lesion,
      respectively. Addition of the Rad7-Rad16 complex to this reconstituted system
      stimulates the incision reaction many fold. The various NER proteins exist in
      vivo as part of multiprotein subassemblies which have been named NEFs (nucleotide
      excision repair factors). Rad14 and Rad1-Rad10 form one subassembly called NEF1,
      the Rad4-Rad23 complex is named NEF2, Rad2 and TFIIH constitute NEF3, and the
      Rad7-Rad16 complex is called NEF4. Although much has been learned from yeast
      about the function of NER genes and proteins in eukaryotes, the underlying
      mechanisms by which damage is recognized, NEFs are assembled at the damage site,
      and the DNA is unwound and incised, remain to be elucidated.

PMID- 10915863
TI  - Enzymatic photoreactivation: 50 years and counting.
AB  - The discovery of enzymatic photoreactivation and of photolyase produced a
      paradigm shift in the way investigators thought about the cellular consequences
      of DNA damage and about how these consequences could be avoided. The in vitro
      photoreactivation system, which utilized crude extracts from Saccharomyces
      cerevisiae as the source of photolyase, not only provided information about the
      mechanism of photoreactivation, but also played an important role in the
      discovery of nucleotide excision repair (NER) and the identification of the
      pyrimidine dimer as the primary lethal lesion induced by 254 nm radiation. More
      recently, mechanistic studies using homogenous purified yeast photolyase have
      yielded insight into how DNA repair enzymes recognize specific structures in DNA,
      while investigations looking at the repair of lesions in chromatin have begun to
      elucidate how DNA repair enzymes deal with damage in the context of eukaryotic
      chromosomes. Additionally, genetic and molecular studies of PHR1, the S.
      cerevisiae gene encoding the apoenzyme of photolyase, have led to the
      identification of previously unknown damage-responsive transcriptional
      regulators.

PMID- 10915864
TI  - Base excision repair in yeast and mammals.
AB  - Base excision repair (BER), as initiated by at least seven different DNA
      glycosylases or by enzymes that cleave DNA at abasic sites, executes the repair
      of a wide variety of DNA damages. Many of these damages arise spontaneously
      because DNA interacts with the cellular milieu, and so BER profoundly influences
      spontaneous mutation rates. In addition, BER provides significant protection
      against the toxic and mutagenic effects of DNA damaging agents present in the
      external environment, and as such is likely to prevent the adverse health effects
      of such agents. BER pathways have been studied in a wide variety of organisms
      (including yeasts) and here we review how these varied studies have shaped our
      current view of human BER.

PMID- 10915865
TI  - Lucky breaks: analysis of recombination in Saccharomyces.

PMID- 10915866
TI  - Tying up loose ends: nonhomologous end-joining in Saccharomyces cerevisiae.
AB  - The ends of chromosomal DNA double-strand breaks (DSBs) can be accurately
      rejoined by at least two discrete pathways, homologous recombination and
      nonhomologous end-joining (NHEJ). The NHEJ pathway is essential for repair of
      specific classes of DSB termini in cells of the budding yeast Saccharomyces
      cerevisiae. Endonuclease-induced DSBs retaining complementary single-stranded DNA
      overhangs are repaired efficiently by end-joining. In contrast, damaged DSB ends
      (e.g., termini produced by ionizing radiation) are poor substrates for this
      pathway. NHEJ repair involves the functions of at least 10 genes, including
      YKU70, YKU80, DNL4, LIF1, SIR2, SIR3, SIR4, RAD50, MRE11, and XRS2. Most or all
      of these genes are required for efficient recombination-independent
      recircularization of linearized plasmids and for rejoining of EcoRI endonuclease
      induced chromosomal DSBs in vivo. Several NHEJ mutants also display aberrant
      processing and rejoining of DSBs that are generated by HO endonuclease or formed
      spontaneously in dicentric plasmids. In addition, all NHEJ genes except DNL4 and
      LIF1 are required for stabilization of telomeric repeat sequences. Each of the
      proteins involved in NHEJ appears to bind, directly or through protein
      associations, with the ends of linear DNA. Enzymatic and/or structural roles in
      the rejoining of DSB termini have been postulated for several proteins within the
      group. Most yeast NHEJ genes have homologues in human cells and many biochemical
      activities and protein:protein interactions have been conserved in higher
      eucaryotes. Similarities and differences between NHEJ repair in yeast and
      mammalian cells are discussed.

PMID- 10915867
TI  - Damage-induced recombination in the yeast Saccharomyces cerevisiae.
AB  - Prokaryotic and eukaryotic cells have developed a network of DNA repair systems
      that restore genomic integrity following DNA damage from endogenous and exogenous
      genotoxic sources. One of the mechanisms used to repair damaged chromosomes is
      genetic recombination, in which information present as a second chromosomal copy
      is used to repair a damaged region of the genome. In this review, I summarized
      what is known about the molecular and cellular mechanisms by which various DNA
      damaging agents induce recombination in yeast. The yeast Saccharomyces cerevisiae
      has served as an excellent model organism to study the induction of
      recombination. It has helped to define the basic phenomenology and to isolate the
      genes involved in the process. Given the evolutionary conservation of the various
      DNA repair systems in eukaryotes, it is likely that the knowledge gathered about
      induced recombination in yeast is applicable to mammalian cells and thus to
      humans. Many carcinogens are known to induce recombination and to cause
      chromosomal rearrangements. An understanding of the mechanisms, by which
      genotoxic agents cause increased levels of recombination will have important
      consequences for the treatment of cancer, and for the assessment of risks arising
      from exposure to genotoxic agents in humans.

PMID- 10915868
TI  - Meiotic chromosome behavior in Saccharomyces cerevisiae and (mostly) mammals.

PMID- 10915869
TI  - The many faces of mismatch repair in meiosis.
AB  - Mismatches, and the proteins that repair them, play multiple roles during meiosis
      from generating the diversity upon which selection acts to preventing the
      intermingling of diverged populations and species. The mechanisms by which the
      mismatch repair proteins accomplish these many roles include gene conversion,
      reciprocal crossing over, mismatch repair-induced recombination and anti
      recombination. This review focuses on recent studies, predominantly in
      Saccharomyces cerevisiae, that have advanced our understanding of the details of
      mismatch repair complexes and how they apply to the diverse roles these proteins
      play in meiosis. These studies have also revealed unexpected and novel functions
      for some of the mismatch repair proteins.

PMID- 10915871
TI  - DNA damage-induced mutation: tolerance via translesion synthesis.
AB  - Translesion synthesis (TLS) appears to be required for most damage-induced
      mutagenesis in the yeast Saccharomyces cerevisiae, whether the damage arises from
      endogenous or exogenous sources. Thus, the production of such mutations seems to
      occur primarily as a consequence of the tolerance of DNA lesions rather than an
      error-prone repair mechanism. Tolerance via TLS in yeast involves proteins
      encoded by members of the RAD6 epistasis group for the repair of ultraviolet (UV)
      photoproducts, in particular two non-essential DNA polymerases that catalyse
      error-free or error-prone TLS. Homologues of these RAD6 group proteins have
      recently been discovered in rodent and/or human cells. Furthermore, the operation
      of error-free TLS in humans has been linked to a reduced risk of UV-induced skin
      cancer, whereas mutations generated by error-prone TLS may increase the risk of
      cancer. In this article, we review and link the evidence for translesion
      synthesis in yeast, and the involvement of nonreplicative DNA polymerases, to
      recent findings in mammalian cells.

PMID- 10915870
TI  - Mismatch repair proteins and mitotic genome stability.
AB  - Mismatch repair (MMR) proteins play a critical role in maintaining the mitotic
      stability of eukaryotic genomes. MMR proteins repair errors made during DNA
      replication and in their absence, mutations accumulate at elevated rates. In
      addition, MMR proteins inhibit recombination between non-identical DNA sequences,
      and hence prevent genome rearrangements resulting from interactions between
      repetitive elements. This review provides an overview of the anti-mutator and
      anti-recombination functions of MMR proteins in the yeast Saccharomyces
      cerevisiae.

PMID- 10915872
TI  - DNA damage checkpoints and DNA replication controls in Saccharomyces cerevisiae.
AB  - In response to genotoxic agents and cell cycle blocks all eukaryotic cells
      activate a set of surveillance mechanims called checkpoints. A subset of these
      mechanisms is represented by the DNA damage checkpoint, which is triggered by DNA
      lesions. The activation of this signal transduction pathway leads to a delay of
      cell cycle progression to prevent replication and segregation of damaged DNA
      molecules, and to induce transcription of several DNA repair genes. The yeast
      Saccharomyces cerevisiae has been invaluable in genetically dissecting the DNA
      damage checkpoint pathway and recent findings have provided new insights into the
      architecture of checkpoint protein complexes, in their order of function and in
      the mechanisms controlling DNA replication in response to DNA damage.

PMID- 10915873
TI  - Repair of UV damage in the fission yeast Schizosaccharomyces pombe.
AB  - This review is concerned with repair and tolerance of UV damage in the fission
      yeast, Schizosaccharomyces pombe and with the differences between Sch. pombe and
      budding yeast, Saccharomyces cerevisiae in their response to UV irradiation. Sch.
      pombe is not as sensitive to ultra-violet radiation as Sac. cerevisiae nor are
      any of its mutants as sensitive as the most sensitive Sac. cerevisiae mutants.
      This can be explained in part by the fact that Sch. pombe, unlike budding yeast
      or mammalian cells, has an extra pathway (UVER) for excision of UV photoproducts
      in addition to nucleotide excision repair (NER). However, even in mutants lacking
      this additional pathway, there are significant differences between the two
      yeasts. Sch. pombe mutants that lack the alternative pathway are still more UV
      resistant than wild-type Sac. cerevisiae; recombination mutants are significantly
      UV sensitive (unlike their Sac. cerevisiae equivalents); mutants lacking the
      second pathway are sensitized to UV by caffeine; and checkpoint mutants are
      relatively more sensitive than the budding yeast equivalents. In addition, Sch.
      pombe has no photolyase. Thus, the response to UV in the two yeasts has a number
      of significant differences, which are not accounted for entirely by the existence
      of two alternative excision repair pathways. The long G2 in Sch. pombe, its well
      developed recombination pathways and efficient cell cycle checkpoints are all
      significant components in survival of UV damage.

PMID- 10915875
TI  - DNA ends: maintenance of chromosome termini versus repair of double strand
      breaks.
AB  - This review focuses on the factors that define the differences between the two
      types of DNA ends encountered by eukaryotic cells: telomeres and double strand
      breaks (DSBs). Although these two types of DNA termini are functionally distinct,
      recent studies have shown that a number of proteins is shared at telomeres and
      sites of DSB repair. The significance of these common components is discussed, as
      well as the types of DNA repair events that can compensate for a defective
      telomere.

PMID- 10915874
TI  - DNA damage and cell cycle control in Schizosaccharomyces pombe.

PMID- 10915876
TI  - Interrelationships between DNA repair and DNA replication.

PMID- 10915877
TI  - Recombination factors of Saccharomyces cerevisiae.
AB  - The budding yeast Saccharomyces cerevisiae has been an excellent genetic and
      biochemical model for our understanding of homologous recombination. Central to
      the process of homologous recombination are the products of the RAD52 epistasis
      group of genes, whose functions we now know include the nucleolytic processing of
      DNA double-stand breaks, the ability to conduct a DNA homology search, and the
      capacity to promote the exchange of genetic information between homologous
      regions on recombining chromosomes. It is also clear that the basic functions of
      the RAD52 group of genes have been highly conserved among eukaryotes. Disruption
      of this important process causes genomic instability, which can result in a
      number of unsavory consequences, including tumorigenesis and cell death.

PMID- 10915878
TI  - The Saccharomyces repair genes at the end of the century.

PMID- 10915879
TI  - Visual motion detection in man is governed by non-retinal mechanisms.
AB  - It is generally assumed that there is no sizable proportion of motion detectors
      in the primate retina. To test this specifically for humans, visual evoked
      potentials (VEPs) and electroretinograms (ERGs) were recorded simultaneously to
      visual motion onset (9.3 degrees /s) of an expanding or contracting 'dartboard'.
      The degree of motion-specific responses in cortex and retina was assessed by
      testing the direction specificity of motion adaptation with three conditions in a
      fully balanced paradigm: motion-onset potentials were measured after adaptation
      to: (1) a stationary pattern; (2) motion in the same direction as the test
      stimulus; and (3) motion in the opposite direction. Motion-onset responses in the
      VEP were dominated by the typical N2 at 150 ms, in the ERG by a positivity at 70
      ms. Onset of contraction or expansion evoked virtually identical VEP and ERG
      responses (P>0.5). Motion adaptation produced strong direction-specific effects
      in the VEP (P<0.05), but not in the ERG (P=0.58): In the adapting and non
      adapting direction the VEP (N2) was reduced by 75 and 50% (P<0.001), the ERG by
      32 and 26% (P<0.01 and 0.05), respectively. The striking difference of the
      direction-specificity of motion adaptation between cortex and retina suggests
      that in humans the vast majority of motion-specific processing occurs beyond the
      retinal ganglion cells.

PMID- 10915880
TI  - Diurnal illumination patterns affect the development of the chick eye.
AB  - Exposure to continuous illumination disrupts normal ocular development in young
      chicks, causing severe corneal flattening, shallow anterior chambers and
      progressive hyperopia ('constant light (CL) effects'). We have studied the
      minimum requirements of a diurnal light cycle to prevent CL effects. (1) Seven
      groups of 10 chicks were reared under a 0 (constant light, CL), or 1, 2, 3,4, 6,
      or 12/12 h (normal) light-dark cycles. It was found that CL effects were
      prevented if the dark period was 4 h or longer. Below 4 h, the effects were dose
      dependent and inversely correlated with the amplitude of the Fourier component of
      illumination at 1 cycle per day (CPD). (2) Three groups of 20 chicks were exposed
      to 4 h of darkness distributed differently over 24 h to vary the amplitude of the
      Fourier component at 1 CPD. It was found that complete suppression of the CL
      effects required that the 4 h of darkness were given in one block and at the same
      time each day. Our results show that normal ocular development in the chick
      requires a minimum of 4 h darkness per day, provided at the same time of the day
      without interruption, and suggest that the light-dark cycle interacts with a
      linear or weakly nonlinear oscillating system.

PMID- 10915881
TI  - Photoreceptor topography of the retina in the New World monkey Cebus apella.
AB  - The number and topographical distribution of photoreceptors was studied in whole
      mounted retinas of Cebus apella. It was estimated a total of 48 million rods and
      3.8 million cones. The average peak foveal cone density and the Nyquist Limit at
      the foveola were estimated as 169, 127 cells/mm(2) and 46.77+/-7.98 cyc/deg,
      respectively. A cone-enriched rim was found near the ora serrata, more noticeable
      in the nasal retina. Rod distribution was asymmetrical along horizontal and
      vertical meridians with a higher density in the dorsal retina. The rod/cone ratio
      was variable and asymmetrical along both meridians.

PMID- 10915882
TI  - Perceived direction during monocular viewing is based on signals of the viewing
      eye only.
AB  - Perceived visual directions are derived from combining retinal signals and
      oculomotor signals. Up to now the general belief is that the oculomotor signals
      of the two eyes are first pooled before they become available for perception of
      depth and direction. In this sense the eyes are believed to act together as one
      unit known as the cyclopean eye. This study, however, shows that during monocular
      viewing in daylight conditions, the perceived directions of objects are indicated
      by their retinal locus in combination with the angular position of the viewing
      eye only, the angular position of the closed eye being irrelevant. This result
      indicates that in binocular vision the integration of left and right eye signals
      first occurs after retinal and oculomotor signals have been integrated of each
      eye separately. This conclusion challenges the prevailing concept of cyclopean
      vision and current views about stereoscopic depth perception.

PMID- 10915883
TI  - Salience from feature contrast: temporal properties of saliency mechanisms.
AB  - Single cell recordings in area V1 of the macaque monkey had suggested that
      saliency effects from orientation contrast might be delayed compared to the
      representation of other stimulus properties. This conjecture was tested in three
      series of experiments on regular line patterns. Experiment 1 investigated the
      time courses of saliency effects evoked either by the onset of a single line or
      by a target that popped out from orientation contrast. Saliency effects from
      orientation contrast developed later than saliency effects related to stimulus
      onset. Experiment 2 measured the detectability of such targets in brief
      presentations. As expected, single line targets were detected at shorter
      presentation times than popout targets with orientation contrast. Experiment 3
      finally investigated the temporal resolution of saliency effects from feature
      contrast in different dimensions. Line arrays with a popout target (e.g. an
      orthogonal line) were alternated with complementary line arrays in which the
      target and the non-target features were exchanged (e.g. all lines were orthogonal
      to those in the previous pattern). Thus, although feature contrast was present in
      every single stimulus display, saliency effects could only develop when
      alternation rates were slow enough to be resolved by the underlying saliency
      mechanisms. Feature flicker of this sort was tested in orientation, motion
      (direction), color and luminance. Saliency mechanisms encoding orientation
      contrast were slower than those encoding differences in luminance or color;
      motion contrast produced intermediate results that also differed between
      subjects.

PMID- 10915884
TI  - On the symmetry between eyes of wavefront aberration and cone directionality.
AB  - There are two optical processes that control the retinal image sampled by the
      photoreceptor array: aberrations of the ocular optics and cone directionality
      (Stiles-Crawford effect). The shape of wavefront aberration and Stiles-Crawford
      functions are known to vary markedly across subjects. In this study we
      investigate in twelve subjects the symmetry between right and left eyes of
      wavefront aberration (measured using a spatially resolved refractometer) and cone
      directionality (measured using an imaging reflectometric technique). The pattern
      of aberrations is in general non-symmetric, suggesting that the development of
      aberrations follow independent paths in many right and left eye pairs. Cone
      directionality is in most cases mirror-symmetric (with one case of direct
      symmetry), suggesting some systematic process underlying cone orientation. Except
      in two subjects, symmetry in these two functions seems to be unrelated. Cone
      directionality apodization improves optical quality, but not optimally in all
      eyes, and it does not tend to increase symmetry in the optical performance of
      left and right eyes.

PMID- 10915885
TI  - ON and OFF S-cone pathways have different long-wave cone inputs.
AB  - Three experiments compared thresholds for S-cone increments and decrements under
      steady and transient adaptation conditions, to investigate whether stimuli of
      both polarities are detected by the same cone-opponent psychophysical mechanism.
      The results could not be accounted for by a standard model of the S-cone
      detection pathway [Polden & Mollon (1980) Proceedings of the Royal Society of
      London, B, 210, 235-272]. In particular, a transient tritanopia detection
      paradigm that measured threshold elevation following the offset of long
      wavelength fields produced different field sensitivities for S-cone increment and
      decrement tests. The decrement field sensitivity function was shifted to shorter
      wavelengths relative to the increment function. L-cone opponency is apparently
      stronger for S-cone increments than for decrements. The most plausible substrates
      of the two different psychophysical detection mechanisms are the ON and OFF
      channels. The results suggest that S-ON (bistratified) and S-OFF ganglion cells
      receive different relative amounts of L- and M-cone input.

PMID- 10915886
TI  - Scotopic sensitivity during adulthood.
AB  - Older adults typically exhibit about a half log unit loss in scotopic sensitivity
      that cannot be attributed to optical factors and retinal disease suggesting a
      neural origin. Little is understood about the developmental course of this neural
      deficit as to whether it first appears in late life or gradually emerges during
      the course of adulthood. To address this developmental issue, scotopic
      sensitivity was measured in 94 adults ranging in age from the 20s to the 80s.
      Thresholds were measured at 27 test loci within a 18 degrees radius field.
      Analogous measurements were made for photopic sensitivity. Fundus photography and
      a grading scale were used to characterize macular health in subjects over age 49
      in order to control for macular disease. Scotopic sensitivity decreased at a rate
      of 0.08 log units per decade; this decline was better fit by a single line model,
      not a bilinear model, implying that the impairment does not suddenly emerge in
      late life but gradually appears over the course of adulthood. Photopic
      sensitivity also decreased in a linear fashion at a rate of 0.04 log units per
      decade. Under these test conditions, the rate of scotopic sensitivity decline
      during adulthood was about double the rate of photopic sensitivity decline.

PMID- 10915887
TI  - The temporal properties of first- and second-order vision.
AB  - Vision is sensitive to first-order modulations of luminance and second-order
      modulations of image contrast. There is now a body of evidence that the two types
      of modulation are detected by separate mechanisms. Some previous experiments on
      motion detection have suggested that the second-order system is quite sluggish
      compared to the first-order system. Here we derive temporal properties of first-
      and second-order vision at threshold from studies of temporal integration and two
      pulse summation. Three types of modulation were tested: luminance gratings alone,
      luminance modulations added to dynamic visual noise, and contrast modulations of
      dynamic noise. Data from the two-pulse summation experiment were used to derive
      impulse response functions for the three types of stimulus. These were then used
      to predict performance in the temporal integration experiment. Temporal frequency
      response functions were obtained as the Fourier transform of impulse responses
      derived from data averaged across two observers. The response to noise-free
      luminance gratings of 2 c/deg was bi-phasic and transient in the time domain, and
      bandpass in the frequency domain. The addition of dynamic noise caused the
      response to become mono-phasic, sustained and low-pass. The response to contrast
      modulated noise (second-order) was also mono-phasic, sustained and low-pass, with
      only a slightly longer integration time than in the first-order case. The
      ultimate roll-off at high frequencies was about the same as for the first-order
      case. We conclude that second-order vision may not be as sluggish as previously
      thought.

PMID- 10915888
TI  - Visual perception and stimulus orientation in cattle.
AB  - The pupil in the eye of adult cattle is oval under contraction with the long axis
      nearly horizontal. Based on simple optophysical facts it is hypothesised that
      visual perception in such eyes is different for stimuli with vertically-separated
      details rather than stimuli with horizontally-separated details. This hypothesis
      was tested with three adult dairy bulls using an operant conditioning technique.
      The bulls had to discriminate a solid white line from broken white lines with
      decreasing interspaces. They solved this task better when the stimuli were
      presented vertically rather than horizontally. This result is discussed in terms
      of visual acuity and related to the topographical anatomy of the eye,
      particularly the pupil.

PMID- 10915889
TI  - Concurrent processing of saccades in visual search.
AB  - We provide evidence that the saccadic system can simultaneously program two
      saccades to different goals. We presented subjects with simple visual search
      displays in which they were required to make a saccade to an odd-colored target
      embedded in an array of distractors. When there was strong competition between
      target and distractor stimuli (due to color priming from previous trials),
      subjects were more likely to make a saccade to a distractor. Such error saccades
      were often followed, after a very short inter-saccadic interval ( approximately
      10-100 ms), by a second saccade to the target. The brevity of these inter
      saccadic intervals suggests that the programming of the two saccades (one to a
      distractor and one to the target) overlapped in time. Using a saccade-contingent
      change in the search display, we show that new visual information presented
      during the initial saccade does not change the goal of the second saccade. This
      supports the idea that, by the end of the first saccade, programming of the
      second saccade is already well underway. We also elicited two-saccade responses
      (similar to those seen in search) using a double-step task, with the first
      saccade directed to the initial target step and the second saccade directed to
      the second target step. If the two saccades are programmed in parallel and
      programming of each saccade is triggered by one of the two target steps, the
      second saccade should occur at a relatively fixed time after the onset of the
      second target step, regardless of the timing of the initial saccade. This
      prediction was confirmed, supporting the idea that the two saccades are
      programmed in parallel. Finally, we observed that the shortest inter-saccadic
      intervals typically followed hypometric initial saccades, suggesting that the
      initial saccade may have been interrupted by the impending second saccade. Using
      predictions from physiological studies of interrupted saccades, we tested this
      hypothesis and found that the hypometric initial saccades did not appear to be
      interrupted in mid-flight. We discuss the significance of our findings for models
      of the saccadic system.

PMID- 10915890
TI  - 'The-skipping' revisited in French: programming saccades to skip the article
      'les'.
AB  - Three experiments were performed to verify O'Regan's (1979) [Perception &
      Psychophysics, 25 (6), 501-509] finding that in reading, the eye moves further
      forward when going towards the word 'THE' than when going towards a three-letter
      verb. The experiments were performed in French instead of English, and compared
      the plural article 'les' with different three-letter verbs. It was confirmed that
      the eye did indeed move about 1.5 letters further in the case of the article
      'les'. Further investigation of the phenomenon suggested that the effect was
      present even when the prior fixation duration was short: Only when prior fixation
      was around 200 ms or less, and additionally when the eye started from a launch
      position that was far from the word, was there a suggestion that the 'les'
      skipping effect disappeared.

PMID- 10915891
TI  - Heading perception and the allocation of attention.
AB  - A central theme in previous studies of heading judgements has been whether the
      retinal flow field can be decomposed to recover the translation component of
      locomotion when flow also contains the effects of gaze rotation. We explored not
      just the effect of moving gaze, but also moving attention away from the locomotor
      path by presenting the case of fixating a road sign and completing different
      attentional tasks during locomotion. Heading errors increased significantly with
      attentional load, in the absence of extra-retinal gaze information. When we
      introduced extra-retinal gaze information with the same tasks this resulted in a
      significant improvement in heading judgements. These results lead us to question
      whether the decomposition argument translates to real-world judgements of
      locomotor heading. If observers need to closely attend to roadside information it
      seems that decomposition is ineffective, whereas if they have the latitude to
      alternate gaze it is unnecessary.

PMID- 10915892
TI  - Effect of a sodium hypochlorite gel on dentin bonding.
AB  - It has been suggested that the hybrid layer (HL) does not play any important role
      in the mechanism of adhesion to dentin. To substantiate this hypothetical
      insignificance of the HL, sodium hypochlorite (NaOCl) has been used to remove
      collagen from etched dentin prior to bonding. OBJECTIVES: The present study was
      conducted to determine the effect of a commercial 10% NaOCl gel on the dentin
      shear bond strengths and HL ultra-morphology of two simplified dentin adhesives.
      The null hypothesis tested was that treatment of etched dentin collagen with
      NaOCl would not compromise dentin bonding. METHODS: The labial surface of eighty
      bovine incisors was polished to expose middle dentin. The specimens were randomly
      assigned to two total-etch adhesive systems (N = 40): Prime&Bond NT (Dentsply
      Caulk); and Single Bond (3M Dental Products Division). After rinsing off the
      etchant, one drop of 10% NaOCl (AD Gel, Kuraray Ltd.) was applied to the etched
      dentin surface and left for 0 (control), 15, 30, or 60 s. The gel was rinsed off
      with water and the dentin surface kept visibly moist prior to the application of
      the adhesive as per manufacturer's instructions. The respective composite resin
      was subsequently applied and light-cured. After 24 h in water at 37 degrees C,
      the specimens were thermocycled for 500 cycles in baths kept at 5 and 55 degrees
      C and the shear bond strengths measured. The data were analyzed with two-way
      ANOVA. For TEM, sixteen dentin disks were taken from middle dentin of extracted
      human third molars, assigned to the eight treatment sequences, and observed.
      RESULTS: The increase in the NaOCl application time resulted in a progressive
      decrease in shear bond strengths for both dentin adhesives. For Single Bond, the
      application of AD Gel for 60 s resulted in a reduction of bond strengths to 38%
      of that obtained for the control. For Prime&Bond NT, the mean bond strength
      obtained when AD Gel was applied for 60 s was 31% of that obtained for the
      control. The application of AD Gel resulted in distinct morphology for each one
      of the two adhesives tested. For Single Bond, the general morphology of the
      collagen network was maintained, regardless of the deproteinization time. The
      interfibrillar space within the collagen network increased with increasing
      deproteinization times. For Prime&Bond NT, the general appearance of the HL was
      maintained for deproteinization times of 15 and 30 s. When the NaOCl gel was
      applied for 60 s, the morphological appearance of the HL lost its fibrillar
      arrangement. While remnants of the collagen fibers were observed in one of the
      dentin disks, the other specimen showed an amorphous structure without any
      discernible HL morphological features. SIGNIFICANCE: The integrity of the
      collagen fibrils left exposed upon acid-etching plays a major role in the
      mechanism of adhesion of the specific adhesive systems tested in this study. The
      intermingling of the adhesive monomers with the filigree of collagen fibers or HL
      should still be considered the paramount dentin bonding mechanism.

PMID- 10915894
TI  - Characterization of resin composites polymerized with plasma arc curing units.
AB  - OBJECTIVES: Newly developed curing units (plasma arc curing units) operate at
      relatively high intensity and are claimed to result in optimum properties of
      resin composites in a short cure time. This study was conducted to determine a
      number of characteristics of resin composites polymerized by plasma arc curing
      units. METHODS: The investigated polymerization characteristics were quantity of
      remaining double bonds, depth of polymerization, flexural strength and modulus,
      and wall-to-wall polymerization contraction. The investigated plasma arc curing
      units were Apollo 95E and 1000 PAC. The conventional curing unit XL 3000 was used
      as baseline. RESULTS: Irradiation with Apollo 95E resulted in a higher quantity
      of remaining double bonds than did XL 3000, whereas the results obtained with
      1000 PAC depended on the resin composite. The depth of cure with the plasma arc
      units was equal to or less than that obtained with the conventional unit,
      depending on the resin composite. The flexural strength did not depend on the
      curing unit. The flexural modulus resulting from curing with Apollo 95E was less
      than that resulting from curing with XL 3000 in 3 out of 4 comparisons. The wall
      to-wall polymerization contraction was equal to or less with the plasma arc units
      than with the conventional unit. SIGNIFICANCE: Plasma arc curing units make it
      possible to polymerize resin composite in much shorter times than conventional
      curing units. However, the polymerization characteristics associated with the
      units may be less than optimal.

PMID- 10915893
TI  - The effect of phosphoric acid concentration on resin tag length and bond strength
      of a photo-cured resin to acid-etched enamel.
AB  - OBJECTIVES: To determine the relationship between depth of penetration and
      tensile bond strength of a photo-cured resin to phosphoric acid etched enamel,
      and the efficacy of enamel etchants that are less aggressive than a concentration
      of 10% H3PO4. METHODS: The tensile bond strength and length of tags produced by a
      photo-cured (20 s) resin consisting of pre-polymerized TMPT/silica in 3% HNPM
      TEGDMA on acid-etched enamel was determined. The enamel etchants tested were
      various concentrations (3-65%) of phosphoric acid. The resin was applied to
      enamel samples that had been abraded with No. 600-grit SiC paper and acid etched
      (30 s) to create test specimens that were loaded to fracture on a testing device.
      The HCl-treated, then cut specimens, were examined under scanning electron
      microscopy and light microscopy. RESULTS: The tensile bond strength (10 MPa) of
      resin to enamel, pre-treated with various acid concentrations did not vary
      significantly. But resin tag length was found to decrease significantly from 22
      microns for 35% H3PO4 to 12 microns for 20% H3PO4 to 9 microns for 5, 10 and 65%
      H3PO4 to 5 microns for 3% H3PO4. SIGNIFICANCE: These findings suggest that the
      length of the tags created by the tested photo-cured resin on phosphoric acid
      etched enamel contributes little to the bond strength of the test specimens, and
      that the adhesive strength of the resin to H3PO4 etched enamel is mainly
      attributable to the resin's ability to penetrate between the enamel crystallites
      and rods. Further, enamel pre-treatment by phosphoric acid etchants of
      concentrations lower than 10% may be satisfactorily employed. The use of less
      aggressive acid concentrations might minimize any potential adverse effects to
      enamel substrates.

PMID- 10915895
TI  - Rheology of dental waxes.
AB  - OBJECTIVES: The rheological properties of waxes are of considerable interest in
      dentistry, yet the only adopted method of characterizing them in this respect is
      arbitrary and uninterpretable. The intention was to identify a means of doing so
      in an objective fashion and to apply it to a variety of products to establish the
      scope of behavior. METHOD: The modified Stokes' falling ball method was used to
      determine the apparent viscosity of 11 waxes over 25-45 degrees C under a wide
      range of loads and, therefore, strain rates. RESULTS: The falling ball method was
      demonstrated to be applicable over at least 7 orders of magnitude in viscosity, 7
      in terminal velocity, and 3 in load. Waxes were shown to be pseudoplastic,
      lacking any identifiable yield point and having marked departures from Newtonian
      behavior. The pseudoplasticity followed a power law, the exponent of which (the
      pseudoplasticity parameter) was temperature dependent in a complex manner, but
      which showed a definite relationship to the reduced temperature, referred to the
      liquidus temperature. A master curve could not be constructed because of this
      variation, but also because of discontinuities in the isothermal contours
      attributed to stress-melting of components of the wax mixture. Stress-melting may
      in part account for the pseudoplasticity. SIGNIFICANCE: A standardized viscosity
      number has been defined at 30 degrees C and under 10 N load as the common
      logarithm of the falling ball apparent viscosity in order to characterize the
      flow behavior of dental waxes with a single convenient number. The shear thinning
      exponent, the reciprocal of the pseudoplasticity parameter, provides a similarly
      convenient measure of the stress-sensitivity of the wax. Direct objective
      comparison of the rheology of dental waxes may now be made, facilitating
      selection by the user through appropriate labeling.

PMID- 10915896
TI  - Resistance of two dentin-bonding agents and a dentin densensitizer to acid
      erosion in vitro.
AB  - OBJECTIVES: To determine the resistance of two dentin-bonding agents (DBAs) and a
      dentin desensitizer to simulated dental erosion. METHODS: Twenty teeth in each of
      three groups of selected premolars, with exposed cervical dentin, were treated
      with one of three dentin surface treatment systems: Gluma Desensitizer (Heraeus
      Kulzer (UK) Ltd), One Coat Bond (Whaledent (UK) Ltd), and Optibond FL (Kerr (UK)
      Ltd) and exposed to water (control) and an erosive challenge (Coca Cola) for 14
      days. Sequential tracings of the specimens were taken, superimposed and the mean
      reduction in densensitizer or DBA thickness and or tooth loss determined.
      RESULTS: A mean loss of 77 microns (s.d. 14.6 microns) of tooth tissue over the
      untreated sites following 14 days exposure to Coca Cola was observed. The
      application of DBAs, as opposed to Gluma Desensistizer alone, over exposed dentin
      surfaces afforded substantial protection against erosion by Coca Cola over the
      period of study. The mean change in vertical profile of teeth treated with a DBA
      was 20 microns (s.d. 14.7 microns), almost four times less than that seen over
      untreated sites. SIGNIFICANCE: With the exception of Gluma Desensitizer, which
      was lost completely, One Coat Bond and Optibond FL demonstrated levels of acid
      dissolution resistance, which would be of potential value clinically.

PMID- 10915898
TI  - Corrosion by galvanic coupling between carbon fiber posts and different alloys.
AB  - OBJECTIVES: The corrosion of metal type (NiCr, copper, etc.) posts in post and
      core restorations has been a well known fact over the last few years. A new
      generation of carbon fiber posts is now playing an extensive role in dental
      prosthetics, but these posts may, in some cases come in contact with alloys used
      for restoration purposes. The objective of this paper is to study the
      electrochemical behaviour of these posts in an artificial SAGF medium (Artificial
      Saliva Gal Fovet) for comparison with that observed for different alloys (gold,
      NiCr and amalgams) in the same medium, and to assess the coupling that might
      occur between these posts and alloys. METHODS: Posts of different diameters (1
      2.1 mm) were molded in resin, thus forming 10 x 3 mm pads that were mounted on a
      rotating electrode. Pads of identical dimensions were also made for each alloy.
      Voltammograms (current-tension curves) were plotted for every material in the
      SAGF medium at 25 degrees C with normal aeration and low aeration (bubbling
      purified argon) using a potentiometer with three electrodes to determine the
      position of the zero current potentials. Evans graphs were then plotted once the
      anode part of the alloy curves and the cathode part of the post curves had been
      processed with computer software. The potentials and the maximum coupling current
      densities were estimated. RESULTS: Posts may be involved in galvanic coupling in
      the presence of oxygen. Galvanic activity in an aerated solution is highly
      probable upon contact with amalgams, but may also occur if the material in
      contact is NiCr alloy. Coupling between precious alloys and posts is improbable
      and can only induce very low currents in the presence of oxygen. SIGNIFICANCE:
      This study devoted to coupling of carbon fiber posts and metals in the mouth,
      attracts attention to the fact that a corrosion reaction can be set-up in the
      infiltration conditions relevant to the prosthetic restoration.

PMID- 10915897
TI  - Dental resin composites containing ceramic whiskers and precured glass ionomer
      particles.
AB  - OBJECTIVES: Glass ionomer, resin-modified glass ionomer, and compomer materials
      are susceptible to brittle fracture and are inadequate for use in large stress
      bearing posterior restorations. The aim of this study was to use ceramic single
      crystal whiskers to reinforce composites formulated with precured glass ionomer,
      and to examine the effects of whisker-to-precured glass ionomer mass ratio on
      mechanical properties, fluoride release, and polishability of the composites.
      METHODS: Silica particles were fused onto silicon nitride whiskers to facilitate
      silanization and to improve whisker retention in the matrix. Hardened glass
      ionomer was ground into a fine powder, mixed with whiskers, and used as fillers
      for a dental resin. Four control materials were also tested: a glass ionomer, a
      resin-modified glass ionomer, a compomer, and a hybrid composite. A three-point
      flexural test was used to measure flexural strength, modulus, and work-of
      fracture. A fluoride ion-selective electrode was used to measure fluoride
      release. Composite surfaces polished simulating clinical procedures were examined
      by SEM and profilometry. RESULTS: At whisker/(whisker + precured glass ionomer)
      mass fractions of 1.0 and 0.91, the whisker composite had a flexural strength in
      MPa (mean (SD); n = 6) of (196 (10)) and (150 (16)), respectively, compared to
      (15 (7)) for glass ionomer, (39 (8)) for resin-modified glass ionomer, (89 (18))
      for compomer, and (120 (16)) for hybrid composite. The whisker composite had a
      cumulative fluoride release of nearly 20% of that of the glass ionomer after 90
      days. The whisker composites had surface roughness comparable to the hybrid resin
      composite. SIGNIFICANCE: Composites filled with precured glass ionomer particles
      and whiskers exhibit moderate fluoride release with improved mechanical
      properties; the whisker-to-glass ionomer ratio is a key microstructural parameter
      that controls fluoride release and mechanical properties.

PMID- 10915899
TI  - Dealloying and electroformation in high-Pd dental alloys.
AB  - OBJECTIVE: The corrosion of high-Pd dental alloys, depending on their
      composition, is postulated to be associated with dealloying and electroformation.
      The aim of this study was to obtain additional information to support these
      postulations. METHODS: The corrosion characteristics of two commercial high-Pd
      alloys, Naturelle (79Pd-10Cu-2Au-9Ga wt%) and Rx 91 (54Pd-37Ag-9Sn), and their
      elemental components were evaluated in a phosphated buffer saline (PBS) solution.
      Indium, a common element in high-Pd alloys, was also included. The corrosion
      characteristics measured for each material were the 24 h open circuit potential
      (OCP) and the potentiodynamic anodic polarization curve. Additionally, the
      surface composition of the two alloys, before and after immersion corrosion in
      PBS for 2 months, was analyzed by X-ray photo electron spectroscopy (XPS).
      RESULTS: Of the pure metals, Ga had the most electroactive OCP followed in order
      by In, Sn, Cu, Ag, Au, and Pd. The anodic polarization data showed all base
      metals to be unstable in PBS. The electroformation of AgCl was evidenced in the
      polarization curve of pure Ag. Both electrochemical characteristics of the PdCu
      based alloy were very similar to that of pure Pd. The PdAg-based alloy displayed
      corrosion behavior resembling that of Ag. XPS data showed that the corrosion of
      the PdCu-based alloy was associated with a decrease in surface content of Cu and
      Ga but an increase in Pd and Au. The PdAg-based alloy surface during corrosion
      showed a decrease in Sn, an increase in Ag, and an unaltered Pd content. The
      behavior of the PdCu-based alloy is attributed to the operation of a galvanic
      interaction that causes dissolution of base metals and surface enrichment with
      primarily Pd. Dealloying, Ag-enrichment, and AgCl formation are thought to have
      contributed to the observed behavior of the PdAg-based alloy. These mechanisms
      are consistent with data from published ion release studies. SIGNIFICANCE: The
      allergenic potential of any Pd alloy is dependent on its propensity to develop a
      Pd-rich surface and thus release Pd+2 ions. The present study, though limited,
      has shown that electrochemical characteristics, namely OCP and polarization
      curves, can be used to identify such alloys. Further studies are warranted to
      evaluate the widespread applicability of these characteristics in distinguishing
      between Pd alloys that are biologically safe and those that are not.

PMID- 10915900
TI  - Postnatal development of 5-HT(1A) receptor expression in rat somatic motoneurons.
AB  - Prior work has established that hypoglossal motoneurons (HMs) change postnatally
      in their response to serotonin (5-HT), in part as a result of a decline in
      expression of 5-HT(1A) receptors. In the current study, two issues were
      addressed. First, using in situ hybridization we found that transient expression
      of 5-HT(1A) receptors occurs in other populations of brainstem (facial and
      trigeminal) and spinal (cervical and lumbar) motoneurons. Second, the
      participation of motoneuronal afferent (serotonergic) and efferent
      (neuromuscular) innervation in inducing and maintaining this decline in
      expression was investigated. Serotonergic innervation of the hypoglossal nucleus
      (nXII) was disrupted in neonatal rats by intra-cisternal injection of the
      serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), and 5-HT(1A) receptor
      mRNA levels in nXII from these rats were assayed at postnatal day 21. In spite of
      an almost complete loss of serotonergic fibers in the region, the postnatal
      decrease in 5-HT(1A) receptor expression by HMs still occurred. To test for
      potential regulation by target-derived factors or by nerve injury, receptor mRNA
      levels were assayed after unilateral transection of the hypoglossal nerve in
      adult rats. Though this treatment resulted in re-induction of developmentally
      transient expression of the p75 neurotrophin receptor, 5-HT(1A) receptor
      expression remained low. Thus, neonatal expression of 5-HT(1A) receptors appears
      to be common to somatic motoneurons, but we found no evidence for changes in
      serotonergic innervation in influencing this expression, nor did we find evidence
      for its regulation by peripheral factors.

PMID- 10915901
TI  - The growth of the feline brain from late fetal into adult life. I. A morphometric
      study of the neocortex and white matter.
AB  - We measured the growth of the neocortex (NCx) and telencephalic white matter (WM)
      in the brain of 64 cats allocated to the following 11 age-groups: fetal (E) 59
      days (birth is at E63-65), postnatal (P) days 1, 7, 15, 30, 45, 60, 90, 120, 180,
      and adult. There were six subjects per group (except for E59, n=4). Using a
      projection microscope and cytochrome oxidase-stained coronal sections, a total of
      4300 and 4325 sections at left and of 4282 and 4264 sections at right were drawn
      for the NCx and for the WM, respectively. With computer assistance, the drawings
      were digitized to calculate mean cross-sectional area and then the mean volume of
      each structure per age-group. The two structures grew heterochronously. In terms
      of percentage of the adult volume, for the left side (both side grew at a similar
      rate), the size of the NCx grew very fast from a 15.7% at E59 to an adult-range
      value of 93.7% at P30. In contrast, the WM grew slowly. Starting at a larger
      volume of 55%, the WM was only 72. 5% of the adult size at P30 reaching an adult
      range value only by P180 (94.7%). After P30, both structures showed a small,
      albeit consistent, left versus right asymmetry with the right size been larger at
      all (but fetal) ages by a margin ranging between 0.4 and 4. 1%. In addition,
      after P30 the NCx tended to overgrow with all groups showing higher values
      relative to adult cats, and reaching significance at P60 (volume higher by 19.2%,
      P<0.01) and at P180 (higher by 14.5%, P<0.05). For the NCx there were no within
      group correlations between volume of the structures and the subjects' body
      weight, while a positive correlation was present for four of the WM postnatal
      groups. There were no correlations between the size of the structures and the sex
      of the cats. The data is discussed in the context of the extant human and animal
      literature and, in the ensuing paper, also within the context of growth of
      subcortical structures.

PMID- 10915902
TI  - The growth of the feline brain from fetal into adult life. II. A morphometric
      study of subcortical nuclei.
AB  - As a continuation of the morphometric studies on the preceding paper, here we
      report on the rate of growth of the caudate nucleus (n.), thalamus, red n., and
      the substantia (s.) nigra using, with few exceptions, the same cohort of cats.
      The same previously used brains (n=64 cats) were allocated to the following age
      groups: fetal (E) 59 days, postnatal (P) days 1, 7, 15, 30, 45, 60, 90, 120, and
      180. Sixteen additional cats, interspersed within the groups, were substituted
      for the red n. and s. nigra studies. There were six subjects per group (except
      for E59, n=4). Using a projection microscope and cytochrome oxidase-stained
      coronal sections, a combined (left plus right sides) total of 4693, 3822, 1636,
      and 1180 sections were drawn for the caudate, thalamus, s. nigra, and red n.,
      respectively. With computer assistance, the drawings were digitized to calculate
      mean cross-sectional areas and then the mean volume of each structure per group.
      The growth time tables for the caudate n., thalamus and s. nigra were fairly
      synchronous. In terms of percentage of the adult volume, for the left side (both
      sides grew at a similar rate), the three structures grew at a fast pace between
      E59 and P30. Thus, at E59 their respective percentages relative to adult volume
      were 23.7, 29.8 and 22.6% and by P30 the percentages were within adult range
      (85.2, 115.1 and 87.5%, respectively). Starting at P30, for the thalamus and at
      P45 for the caudate n., there was a consistent tendency to an overgrow which
      ranged between 4.3 and 30.9% (at P180, P<0.5) for the caudate and between 0.3 and
      15.1% for the thalamus. In addition, starting at P30, the right thalamus tended
      to be consistently larger than the left by a margin ranging between 0.5 and 11.2%
      (P120, P<0.05). The red n. grew at a different, slower pace. Starting from a
      fetal volume equivalent to an 18.6% of adult size, its volume was only a 61.0% of
      the adult value at P30 and came within range of adulthood size only by P60 (81.
      3%). Neither the s. nigra nor the red n. showed any consistent tendency to
      overgrow or to asymmetry. These findings are discussed in the context of the
      literature. Furthermore, we discuss general conclusions and considerations
      pertaining to both papers as well as draw comparisons with the maturational time
      tables of other developmental landmarks in cats. Finally, in a comparison with
      growth of human brain structures, we point at the limitations and complexities
      involved in studying human material and, noting interspecies similarities, we
      propose that the present data from an advanced gyrencephalic mammal may form the
      bases for a model of structures maturation in humans.

PMID- 10915903
TI  - Effects of unilateral deprivation in postnatal development of the olfactory bulb
      in an altricial rodent, the gerbil (Meriones unguiculatus).
AB  - To establish if olfactory bulb sensitivity to functional deprivation is related
      to the degree of development at birth, we studied the effects of surgical closure
      of one naris in the gerbil olfactory bulb development. The naris closure was
      performed at three different ages: at birth, P7 and P14 and maintained for 30 or
      60 days. In coronal sections we measured total bulbar surface area and surface
      area of the different bulbar layers establishing an estimate multiple regression
      model for the percentage of surface area decrease in the deprived bulb related to
      non deprived one. The internal and external plexiform layers are the most
      sensitive layers to deprivation and age and duration of deprivation were factors
      in their mathematical models. The glomerular layer showed a surface reduction of
      about 25% without dependence either on age or duration. The deprived glomerular
      layer showed a much lower tyrosine hydroxylase-immunoreactivity and
      immunoreactive cell density than those in the non deprived one. However,
      differences in calbindin-immunoreactive and NADPH-diaphorase positive cell
      density between deprived and non deprived glomerular layer were not significant.
      Our results indicate that olfactory bulb sensitivity to functional deprivation is
      not related to the degree of precocity and changes in age and duration of
      deprivation cause different effects on the olfactory bulb layers.

PMID- 10915904
TI  - The development of excitatory capability in Aplysia californica bag cells
      observed in cohorts.
AB  - The bag cells of Aplysia release egg laying hormone in sexually mature animals.
      Bag cells cannot sustain the long-lasting excitatory afterdischarge (AD) required
      for hormone release prior to sexual maturity (T.A. Nick, L.K. Kaczmarek, T.J.
      Carew, Ionic currents underlying developmental regulation of repetitive firing in
      Aplysia bag cell neurons, J. Neurosci. 1996;16:7583-7598; L.A. Fieber,
      Characterization of Na(+) and Ca(2+) currents in bag cells of sexually immature
      Aplysia californica, J. Exp. Biol. 1998;201:745-754). To investigate the
      development of bag cell excitability, whole-cell voltage-clamp experiments were
      executed in dissociated bag cells from four cohorts (batches) of hatchery-reared
      A. californica maintained at 13-15 degrees C. K(+) current densities,
      representing the sum of at least four different outward K(+) currents (Nick et
      al., 1996), declined significantly as a function of age, beginning at least 2-3
      months before sexual maturity. The K(+) current decreases coincided with the
      first appearance of Na(+) and Ca(2+) currents in bag cells, which occurred at
      ages 6-7 months. Whole cell K(+) currents were not decreased significantly by a
      cAMP analog earlier than 1 month prior to the onset of reproductive activity. The
      frequency of observing Na(+) currents in whole cell recordings was low for
      developmental times earlier than sexual maturity. In one winter batch, both
      control and PMA-treated Na(+) currents increased significantly with age, and PMA
      treated current densities were significantly greater than controls, but the other
      two batches studied had significant differences in Na(+) current frequency only
      at sexual maturity. Ca(2+) currents were reliably measured in more cells than
      were Na(+) currents. The Ca(2+) current frequency increased significantly with
      maturity in one winter batch. Ca(2+) currents were significantly increased by
      phorbol ester treatment beginning 6-8 weeks before reproductive activity in the
      two winter batches. These observations support the hypothesis that bag cell
      excitability is not fully developed until shortly before sexual maturity.

PMID- 10915905
TI  - Intrinsic properties of the developing motor cortex in the rat: in vitro axons
      from the medial somatomotor cortex grow faster than axons from the lateral
      somatomotor cortex.
AB  - The axons that originate in the medial somatomotor cortex of the rat depart,
      during development, after those from the lateral somatomotor cortex, yet they
      arrive in the cervical spinal cord first. Either the medially originating axons
      elongate faster, or the laterally originating ones pause along the descent
      pathway. To investigate the presence of an intrinsic difference of the axonal
      elongation velocity between the lateral and medial somatomotor cortical areas, we
      cultured explants taken from these areas for 2 days, and measured the length of
      the outgrowth. After 2 days the explants were surrounded by a radiate corona of
      axons of which the longest measured 1.95 mm. A significant difference was
      detected between the medial and lateral somatomotor cortical areas in vitro.
      Axons originating from explants taken from the medial somatomotor cortical area
      are, after 2 days in culture, on average 0.16 mm longer than those from the
      lateral somatomotor cortical area. Though the observed difference is not large
      enough to allow for the overtaking observed in vivo, it does indicate that
      intrinsic differences exist within the developing rat somatomotor cortex. This in
      turn indicates that intrinsic cortical traits not only influence regionalization
      and targeting behavior of cortical projection neurons, but also their axonal
      elongation speed.

PMID- 10915906
TI  - Cell cycle kinetics and immunohistochemical characterization of dissociated fetal
      neocortical cultures: evidence that differentiated neurons have mitotic capacity.
AB  - Neurons in the neocortex (regardless of their developmental state) are considered
      to be post-mitotic and incapable of dividing. We used dissociated primary
      cultures derived from the neocortices of 16-day-old fetuses to test the counter
      hypothesis, that is, differentiating neocortical neurons can divide. The cultured
      cells experienced considerable cell death, yet the number of viable cells
      remained relatively constant over the first 5 days in vitro. The implication was
      that the cultures contained proliferating cells. This was confirmed with a
      [(3)H]thymidine ([3H]dT) incorporation study and cumulative bromodeoxyuridine
      labeling. In fact, over 1/4 of the cells were cycling and the length of the cell
      cycle was 20.0 h; kinetics which mirror those of the developing cortex in vivo.
      This population of proliferating cells was eliminated by 48 h treatment with
      fluorodeoxyuridine. Immunohistochemical procedures determined that most cultured
      cells (>/=90%) expressed proteins associated with differentiating or mature
      neurons, e.g., neurofilament (NF) 200 and isoforms of microtubule-associated
      protein (MAP) 2. Markers for immature neurons (e.g., nestin) were expressed by
      10% of the cells. In contrast, markers for glia and their precursors were
      expressed by </=2% of the population. Double-labeling with [3H]dT and a neural
      specific antibody showed that cells expressing an antigen for immature neurons
      constituted most of the proliferating cells, however, a considerable number of
      [3H]dT-labeled cells expressed markers for differentiating neurons (e.g., NF200
      and MAP2). Thus, differentiating neocortical neurons can be mitotically active
      and it appears that differentiating neurons are derived from both the ventricular
      and subventricular proliferative zones.

PMID- 10915907
TI  - Neurotrophic effect of basic fibroblast growth factor is mediated by the p42/p44
      mitogen-activated protein kinase cascade in cultured rat cortical neurons.
AB  - Basic fibroblast growth factor (bFGF) has been reported to support the survival
      of brain neurons. In the present study, we investigated whether the neurotrophic
      effect of bFGF is mediated by the mitogen-activated protein kinase (MAPK) cascade
      in cultured rat cerebral cortical neurons. Recombinant human bFGF (0.1-10 ng/ml)
      induced phosphorylation of p44/42 MAPK (ERK1/2) in a concentration- and time
      dependent manner. bFGF-induced ERK1/2 phosphorylation and promotion of neuronal
      survival were both blocked by U0126 and PD98059, inhibitors of the MAPK
      activating enzyme MEK. These results suggest that the MEK/ERK signal transduction
      cascade is involved in the neurotrophic effect of bFGF.

PMID- 10915909
TI  - Maturation of locomotor and Fos responses to the NMDA antagonists, PCP and MK
      801.
AB  - Antagonists at the N-methyl-D-aspartate (NMDA)-type glutamate receptor, such as
      phencyclidine (PCP) and dizocilpine (MK-801), are well-known to evoke increases
      in locomotor activity in adult rats and mice. However, little is known about the
      effects of NMDA antagonists on locomotor activity as a function of development.
      The present study examined locomotor responses to PCP or MK-801 in male rats of
      varying ages and found that prepubertal rats were more sensitive to the locomotor
      elevating effects of PCP (1.5 mg/kg and 3. 0 mg/kg, s.c.) than were adults.
      Locomotor responses to MK-801 (0.1 and 0.2 mg/kg, s.c.) were not dependent on
      age. The age-dependent response to PCP may be related to developmental events in
      the motor cortex, since more Fos-immunoreactive neurons were observed in the
      motor cortex of prepubertal animals after PCP administration relative to adult
      animals. An opposite pattern of age-dependent Fos responses was observed in the
      posterior retrosplenial cortex. The results suggest that locomotor responses to
      NMDA antagonists can be influenced in an age- and drug-dependent manner and that
      maturational events in the motor cortex may modify responses to PCP.

PMID- 10915908
TI  - Dopaminergic phenotype of hNT cells in vitro.
AB  - We investigated the catecholaminergic nature of cultured hNT neurons previously
      treated either for 4 or 5 weeks with retinoic acid (RA). There were significantly
      more tyrosine hydroxylase (TH)-positive neurons (60%) in cultures treated for 4
      weeks with RA compared to 5 week-treated cultures (</=15%). Furthermore, numerous
      TH-positive hNT cells were also immunoreactive to dopamine transporter (DAT),
      dopamine receptor (D2) and aldehyde dehydrogenase (AHD-2), an enzyme exclusively
      expressed by dopaminergic (DA) ventral mesencephalic (VM) precursors. Thus this
      cell line has all the necessary cellular machinery to produce functional DA
      neurons and therefore is a good alternative tissue source to fetal VM.

PMID- 10915911
TI  - Corrigendum to 'Prenatal morphine exposure alters susceptibility to bicuculline
      seizures in a sex- and age-specific manner'.

PMID- 10915910
TI  - Inhibition of mitogen-activated protein kinase kinase blocks proliferation of
      neural progenitor cells.
AB  - Nestin-expressing neural progenitor (NP) cells have been isolated from the
      subventricular zone (SVZ) of the brain and propagated with epidermal growth
      factor (EGF) and basic fibroblast growth factor (bFGF). In other neural cell
      types it has been shown that EGF and bFGF activate cell surface receptors
      involved in the mitogen-activated protein kinase (MAPK) signal pathway. To
      examine this issue in NP cells, we isolated primary SVZ cells and stimulated them
      with EGF and bFGF and then used a phosphorylation-specific antibody to detect
      activated MAPK by immunofluorescent staining or Western blotting. The addition of
      growth factors activated MAPK transiently in cells that co-expressed nestin. A
      distinct phospho-MAPK signal was also detected in nestin-positive cells with
      mitotic chromosomes. A novel MAPK kinase (MEK1) inhibitor U0126 blocked the
      activation of MAPK and the proliferation of primary cells more effectively than
      the same concentration of PD98059. After exposure of cells to U0126 for 10 days,
      we noted that there was a significant reduction in the number of cells that
      expressed nestin and an increase in the percentage of apoptotic cells. These data
      provide evidence that activation of MAPK by MEK1 is important for the
      proliferation of NP cells.

PMID- 10915912
TI  - Thwarting of behaviour in different contexts and the gakel-call in the laying
      hen.
AB  - Earlier studies have shown that thwarting of feeding behaviour in the laying hen
      is expressed through a specific vocalisation, the gakel-call. The first aim of
      this study was to investigate whether the effect of deprivation per se on the
      occurrence of gakel-calls can be distinguished from the effect of the additional
      frustration. Frustration is defined as the state of an animal that results from
      nonreward in the expectancy of reward. The second aim was to investigate whether
      the occurrence of gakel-calls is restricted to a food context or whether it can
      be regarded as an expression of frustration in general. For this purpose, 20 hens
      were deprived of food, water and dustbath. After deprivation at a fixed time, a
      cue was given and the hens were rewarded with access to food, water or dust
      during a 15-min session on 4 consecutive days. On the fifth day, they were
      thwarted in the associated behaviours by blocking the access to these
      commodities, after the hens had been presented the signal that previously
      preceded the reward. We then recorded behaviours that might reflect the state of
      frustration in three 15-min periods. The period "Pre-Frustration" started 15 min
      before "Frustration". This, in turn, was followed by the period "Post
      frustration" in which the hens were rewarded again. Nesting behaviour was
      thwarted by blocking the access to the nest (Frustration) after a hen had reached
      the last stage of its prelaying behaviour.In the food, water and dustbath
      context, deprivation elicited gakel-calls. The additional frustration resulted in
      a higher number of gakel-calls in all contexts except the food context. However,
      together with the findings of previous experiments, the results of this study
      suggest that frustration, in general, is expressed through the gakel-call.
      Frustration in the nest context elicited more gakel-calls than the other
      contexts. This latter finding is discussed in the light of the occurrence of the
      gakel-call under natural circumstances.

PMID- 10915913
TI  - The vocal expression of feeding motivation and frustration in the domestic laying
      hen, Gallus gallus domesticus.
AB  - Thwarting of feeding behaviour in the laying hen results in an increase in
      stereotyped pacing, displacement preening, and the gakel-call. These behaviours
      therefore reflect the frustration arousal caused by the thwarting of feeding
      behaviour. This raises the question whether the level of frustration also varies
      with the intensity of the motivation to perform the thwarted behaviour. This
      study investigated the relationship between the intensity of the motivation and
      level of frustration on the one hand and the gakel-call on the other hand. In
      Experiment 1, the strength of the motivation to feed was varied by thwarting hens
      in their feeding behaviour in an operant procedure after different durations of
      food deprivation (0, 8, 23 and 47 h). Trend analysis showed that with increasing
      hunger state, an increasing number of gakel-calls was given. No effect of
      treatments on temporal characteristics of the gakel-call was found. In Experiment
      2, the level of frustration was varied by reducing or increasing the duration of
      access to food for food-deprived hens compared to the duration of access during
      training. It was assumed that a shorter duration of access to food compared to
      training would elicit frustration, which in turn would affect the performance of
      behaviours indicative of thwarting. However, we found neither a relation between
      the number of gakel-calls nor the temporal features of the gakel-call and the
      duration of access to food. Possibly, the differences between treatments were not
      large enough to induce differences in frustration level. Also, other factors that
      might have influenced the motivation are discussed.

PMID- 10915914
TI  - Do female broiler breeder fowl display a preference for broiler breeder or laying
      strain males in a Y-maze test?
AB  - In recent years, the commercial broiler breeder industry has reported problems of
      male aggression towards females [Millman, S.T., 1999. An investigation into
      extreme aggressiveness of broiler breeder males. Unpublished PhD Thesis,
      University of Guelph]. Although this aggression is shown by the males and is
      apparently a defect in their behaviour [Millman, S.T., Duncan, I.J.H., 2000.
      Strain differences in aggressiveness of male domestic fowl in response to a male
      model. Appl. Anim. Behav. Sci. 66, pp. 217-233], it is also possible that it
      stems in some way from the females. For example, broiler breeder females may not
      be receptive to male courtship advances, and may avoid males, thus causing
      frustration in otherwise normal males. The objective of this study was to examine
      mate preference by broiler breeder females and the effects of sexual experience
      on preference. A total of 24 mature, broiler breeder females were individually
      tested in a Y-maze, with females choosing between a broiler breeder male and a
      laying strain male. Females were tested using male models and tethered live
      males, both when the females were sexually inexperienced and after they had been
      housed with broiler breeder or laying strain males for 6 weeks.Females did not
      display a male-strain preference when tested with models, but sexually
      experienced females displayed some evidence of a preference for laying strain
      males in tests with live males, which did not reach statistical significance
      (P<0.10). Live males were a stronger attractant for sexually experienced females
      than were models (P<0.005). Individual females tested with the same pair of males
      showed different preferences, suggesting females used male behaviour as a basis
      for their choices, and not male morphology.In conclusion, we found no evidence
      that broiler breeder females inherently discriminate against broiler breeder
      males.

PMID- 10915915
TI  - Pecking preferences and pre-dispositions in domestic chicks: implications for the
      development of environmental enrichment devices.
AB  - Environmental enrichment is thought likely to benefit chickens and farmers in
      many ways; these include reduced fearfulness and feather pecking and improved
      productivity. Enrichment devices would intuitively be more effective if they
      reliably attracted and sustained appreciable interest but many fail to do so.
      This may reflect the fact that the choice of stimuli often reflects availability
      and human preconceptions rather than a critical consideration of the birds'
      preferences and pre-dispositions. We had previously identified string as a
      particularly attractive pecking stimulus for chicks and adult hens (Gallus gallus
      domesticus) of a laying strain (ISA Brown). In the present study we found that
      chicks of another laying strain (Lohmann Brown) also pecked sooner and more at a
      bunch of string than at chains or beads (Experiment 1). White or yellow strings
      were preferred to red, green or blue ones (Experiment 2) and white string
      elicited more pecking than did combinations of white and yellow or of all five
      colours (Experiment 3). Varying the length and width of the bunches of string
      exerted no detectable effects on pecking (Experiment 4) whereas incorporating
      small, shiny beads in the white string devices actually reduced pecking
      (Experiment 5). Virtually all the devices elicited progressively more interest
      with repeated presentation; this trend was particularly marked for white string.
      Collectively, the present findings demonstrate that young domestic chicks have
      clear and specific pecking preferences. Although the magnitude of response varied
      across experiments, white string consistently elicited the most interest. Our two
      main conclusions are: (i) white or yellow strings were particularly attractive
      stimuli that drew increasing interest, at least in the short term, and (ii)
      simple devices were preferred to more complex ones, or at least to those used
      here.

PMID- 10915916
TI  - Taste threshold determination and side-preference in captive cockatiels
      (Nymphicus hollandicus).
AB  - The taste thresholds of caged cockatiels (Nymphicus hollandicus) for aqueous
      solutions of sodium chloride, citric acid, and sucrose were studied using two
      choice taste-preference tests. The effects of location on the threshold were
      tested by putting the flavored solution in either the preferred or non-preferred
      locations (i.e. sides of cages) and offering water in the opposite location. Four
      parameters (total consumption, consumption from preferred side, consumption from
      non-preferred side, and proportion of test solution consumed) were measured at
      the end of 3-day test periods. Experiments were repeated with increasing
      concentration of test flavors until intake variables were significantly (p<0.05)
      affected. The results showed that birds distinguished (p<0.05) between purified
      water and 0.16 mol l(-1) sodium chloride, 0.36 mol l(-1) sucrose, or pH 5.5
      citric acid. The likelihood of detecting a taste threshold was greater for sodium
      chloride and citric acid when these solutions were placed on the preferred side.
      In contrast, sucrose sensitivity was greater when this solution was offered on
      the non-preferred side.

PMID- 10915918
TI  - Hormone replacement therapy and breast cancer.
AB  - There is considerable evidence that the risk of breast cancer is related to
      ovarian function. However, the effect of postmenopausal hormone replacement
      therapy (HRT) on breast cancer risk continues to be debated in the absence of
      data from randomised controlled trials. Observational studies suggest that HRT
      probably promotes the growth of pre-existing breast cancers rather than
      initiating malignant transformation of breast epithelial cells but without
      exerting an obviously detrimental effect on disease-specific mortality. The
      controversy surrounding HRT and breast cancer has become additionally more
      complex as a result of the dilemma faced by clinicians advising women rendered
      oestrogen-deficient by breast cancer therapy. Whilst HRT is currently contra
      indicated due to theoretical concerns that it will promote disease recurrence,
      its increasing, ad hoc prescription to symptomatic breast cancer patients has not
      been associated with an increase in disease recurrence. Large-scale randomised
      trials of HRT in healthy women and breast cancer survivors are now ongoing but it
      will be some years before useful clinical information becomes available. Until
      then, the limitations and biases implicit as a result of the design of
      observational studies must be borne in mind when interpreting such studies.

PMID- 10915917
TI  - Cardioprotective effects of ovarian hormones and the HERS in perspective.
AB  - The increased population of women in menopause living in the industrialized
      countries is associated with an increase of diseases which are dependent or
      facilitated by a state of estrogen deficiency such as cardiovascular and
      cerebrovascular diseases. Several studies have shown that estrogen replacement
      therapy reduces the occurrence of coronary and may be of cerebrovascular disease
      by nearly 50% in treated women compared to non-users. These findings are
      supported by the evidence that estrogens have a beneficial effect on cholesterol
      metabolism and deposition, contributing to the inhibition of atherosclerotic
      plaque formation in arterial walls as well as a direct effect on the vessel wall.
      Progestins may, in some cases, counteract the beneficial effect of estrogens upon
      cardiovascular functions. More androgenic progestins may have a detrimental
      effect upon vascular reactivity while less androgenic progestins seem not to
      reduce the beneficial effect of estrogens. Of interest, continuous combined
      administration of hormone replacement therapy seem to be preferable for women
      with coronary artery disease or for those with increased cardiovascular risk.
      Case-control and cohort studies have shown that estrogen progestin therapy is
      associated with a significant reduction of cardiovascular mortality and
      morbidity. The HERS study has added critical data regarding the cardioprotective
      effect of hormone replacement therapy in elderly women with proven coronary
      artery disease. Because of the several methodological and statistical flaws of
      the HERS study, further studies are warranted to evaluate the effect of hormone
      replacement therapy on cardiovascular prognosis. Large scale randomized studies
      will evaluate the effect of estrogen and estrogen-progestin replacement therapy
      upon cardiovascular events in menopausal women. Until completion of these studies
      hormone replacement therapy in women with increased cardiovascular risk should be
      seen with no enthusiasm but also with no fear.

PMID- 10915919
TI  - Recent insights into the varying activity of estrogens.
AB  - Recent advances have added substantially to our understanding of the biology of
      estrogens. Estrogens are no longer considered to differ only in potency. Two
      estrogens can have similar effects in one tissue and very different effects in
      another. Additionally, an estrogen can have different effects in different
      tissues. It is now recognized that there are at least two estrogen receptors, ER
      alpha and ER-beta, and that it is quite likely that estrogens also work through
      non-genomic mechanisms. The development of new methods of chromatographic
      separation has aided substantially in our ability to characterize the composition
      of Premarin, including the identification of estradiene, the fourth-most abundant
      estrogen in Premarin. Recent studies have contributed to our understanding of the
      unique profile of Delta(8,9) dehydroestrone sulfate, another of the Premarin
      estrogens. It was found that Delta(8,9) dehydroestrone sulfate is an active
      estrogen with a distinct pharmacological profile that results in significant
      clinical activity in vasomotor, neuroendocrine and bone preservation parameters.
      However, it displayed little or no efficacy, at the dose studied, on other
      peripheral parameters normally affected by classical estrogens. Increasing
      knowledge of the unique profiles of the Premarin components, as well as their
      complex interaction, will help to increase our understanding of the clinical
      profile of Premarin.

PMID- 10915920
TI  - The estrogen replacement therapy of the Women's Health Initiative promotes the
      cellular mechanisms of memory and neuronal survival in neurons vulnerable to
      Alzheimer's disease.
AB  - OBJECTIVES: The current study investigated the neurotrophic and neuroprotective
      action of the complex formulation of conjugated equine estrogens (CEEs), the most
      frequently prescribed estrogen replacement therapy in the United States and the
      estrogen replacement therapy of the Women's Health Initiative. METHODS:
      Videomicroscopic, morphologic and biochemical analyses were conducted in primary
      cultures of hippocampal neurons to determine the neurotrophic and neuroprotective
      properties of CEEs. RESULTS: Results of these analyses demonstrated that CEEs
      significantly increased hippocampal neuronal outgrowth, a cellular marker of
      memory formation. Dose response analyses indicated that the lowest effective
      concentration of CEEs exerted the maximal neurotrophic effect. Results of
      neuroprotection studies demonstrated that CEES induced highly significant
      neuroprotection against beta amyloid(25-35), hydrogen peroxide and glutamate
      induced toxicity. CONCLUSIONS: CEEs induced cellular markers of memory function
      in neurons critical to memory and vulnerable to negative effects of aging and
      Alzheimer's disease. In addition, CEEs significantly and potently protected
      neurons against toxic insults associated with Alzheimer's disease. Because CEEs
      are the estrogen replacement therapy of the Women's Health Initiative, results of
      the current study could provide cellular mechanisms for effects of CEEs on
      cognitive function and risk of Alzheimer's disease derived from this prospective
      clinical trial.

PMID- 10915921
TI  - Biodistribution of fluoresceinated dextran using novel nanoparticles evading
      reticuloendothelial system.
AB  - The rapid clearance of circulating nanoparticles from the blood stream coupled
      with their high uptake by liver and spleen has thus far been overcome by reducing
      the particle size, and by making the particle surface hydrophilic with poloxamers
      and poloxamines. We have prepared hydrogel nanoparticles of polyvinylpyrrolidone
      of a size less than 100 nm diameter with precise size distribution. Since the
      inner cores of these particles are also hydrophilic, these particles are capable
      of encapsulating water-soluble compounds. Biodistribution of these particles
      shows practically negligible (<1%) uptake by the macrophages in liver and spleen,
      and approximately 5-10% of these particles remain in circulation even 8 h after
      i.v. injection. Increasing the surface hydrophobicity as well as particle size
      can increase the RES uptake of these particles. Because of longer residence in
      blood, the hydrogel nanoparticles have potential therapeutic applications
      particularly in cancer: the water-soluble cytotoxic agents encapsulated in these
      particles can be targeted to tumors while minimizing the likelihood of toxicity
      to reticuloendothelial system (RES).

PMID- 10915922
TI  - A novel approach for delivery of enzyme drugs: preliminary demonstration of
      feasibility and utility in vitro.
AB  - A novel heparin/protamine-based approach for delivery of enzyme drugs without
      associated toxic effects has been proposed. This approach would allow an enzyme
      drug to be administered in an inactive (i.e. pro-drug) form and then released at
      the target site in an active form using protamine as the triggering agent. The
      pro-drug and the triggered release features of this approach would permit the
      enzyme drug to act specifically and only on its target substrates while sparing
      normal substrates, thereby alleviating unwanted toxic effects. The in vitro
      feasibility of the approach has been successfully demonstrated using trypsin as
      the model protease drug. In addition, the utility of the approach has also been
      demonstrated by applying the system in delivering streptokinase, one of the most
      widely used clinical drugs in thrombolytic therapy. This approach may open up the
      possibility of developing a wide range of new catalytic drugs that are initially
      thought to be impossible for therapeutic use due to their potent toxic effects.

PMID- 10915923
TI  - Fronts movement as a useful tool for hydrophilic matrix release mechanism
      elucidation.
AB  - The purpose of this study was to modify the fronts movement method proposed by
      Colombo et al. in order to apply it to uncoloured drugs and hydrophilic non
      swellable matrices. Matrix tablets were prepared using theophylline as a model
      drug and sodium carboxymethylcellulose (NaCMC) or a new graft copolymer,
      hydroxypropylcellulose methylmethacrylate dried by lyophilization (HCMMAL), as
      polymer carriers. Drug release experiments were performed from the whole tablets.
      Radial drug release and fronts movement were also evaluated using special devices
      consisting of two Plexiglass(R) discs joined by means of four stainless steel
      screws. Release kinetics were determined by means of Higuchi, Korsmeyer and
      Peppas equations and were related to the fronts movement data. The analysis of
      drug release and fronts movement kinetics revealed a different release mechanism
      for both matrices. Drug release from NaCMC matrices was mostly controlled by
      relaxation, whereas drug diffusion through the porous network regulated drug
      release from HCMMAL matrices. A reduction in the surface exposed to the
      dissolution medium led to a decrease in the drug release rate, but the release
      mechanism was not essentially modified. Fronts movement was shown as a useful
      tool for matrix release mechanism elucidation. A new denomination for the
      different fronts observed in HCMMAL matrices was proposed.

PMID- 10915925
TI  - Relationship between potency and boiling point of general anesthetics: a
      thermodynamic consideration.
AB  - The most important group of nonspecific drugs is that of the general anesthetics.
      These nonspecific compounds vary greatly in structure, from noble gases such as
      Ar or Xe to complex steroids. Since the development of clinical anesthesia over a
      century ago, there has been a vast amount of research and speculation concerning
      the mechanism of action of general anesthetics. Despite these efforts, the exact
      mechanism remains unknown. Many theories of narcosis do not explain how
      unconsciousness is produced at a molecular level, but instead relate some
      physicochemical property of anesthetic agents to their anesthetic potencies. In
      this paper, we address some of those physicochemical properties, with more
      emphasis on correlating the anesthetic potency of volatile anesthetics to their
      boiling points based on thermodynamic principles.

PMID- 10915924
TI  - Chitosan microspheres in PLG films as devices for cytarabine release.
AB  - Cytarabine was included in chitosan microspheres and several of these
      microspheres were embedded in a poly(lactide-co-glycolide) (PLG) film to
      constitute a comatrix system, to develop a prolonged release form. Chitosan
      microspheres, in the range of 92+/-65 microm, having good spherical geometry and
      a smooth surface incorporating cytarabine, were prepared. The cytarabine amount
      included in chitosan microspheres was 43.7 microg of ara-C per milligram
      microsphere. The incorporation efficiency of the cytarabine in microspheres was
      70.6%. Total cytarabine release from microspheres in vitro was detected at 48 h.
      Inclusion of cytarabine-loaded microspheres in poly(lactide-co-glycolide) film
      initiated a slower release of the drug and, in this way, the maximum of
      cytarabine released (80%) took place in vitro at 94.5 h. Comatrices, with 8.7 mg
      of cytarabine, signifying a dose of 34.5 microg/kg, were subcutaneously implanted
      in the back of rats. Maximum plasma cytarabine concentration was 18.5+/-1.5
      microg/ml, 48 h after the device implantation and the drug was detected in plasma
      for 13 days. The histological studies show a slow degradative process. After 6
      months of implantation, most of the microspheres of the matrix seemed to be
      intact, the comatrix appeared surrounded by conjunctive tissue and small blood
      vessels and nerve packets were detected in the periphery of the implant.

PMID- 10915926
TI  - Kinetic study of the reaction of sulfamethoxazole and glucose under acidic
      conditions: I. Effect of pH and temperature.
AB  - The kinetics of the reaction of sulfamethoxazole (SMX) in 5% w/v glucose to form
      the corresponding alpha- and beta-glucosylamines over the pH range of 0.80-6.88
      at 37 degrees C has been investigated. The identity of the glucosylamines was
      determined by 1H-nuclear magnetic resonance spectroscopy of an authentic sample
      of the alpha-glucosylamine (USP) and the reaction products, and by
      interconversion of this compound to the corresponding beta-anomer. The reaction
      followed pseudo first-order reversible kinetics and involved specific acid and
      general acid-base catalysis. The pH-rate profile demonstrated that over the pH
      range of 0.80-2.90 and 5.50-6. 88 the reactions were dependent on H(+)
      concentration but pH independent between pH 3.00-5.45, which reflects the
      influence of ionization of SMX and the glucosylamines on the reversible reaction.
      Interpretation of the data with respect to kinetic models and rate equations for
      the formation and hydrolysis of the glucosylamines was investigated. Temperature
      dependence studies followed the Arrhenius equation with an Ea of 49.28 kJ mol(-1)
      for the forward and 63.46 kJ mol(-1) for the reverse reaction at pH 2.89
      respectively.

PMID- 10915927
TI  - Influence of vitamin E TPGS on the properties of hydrophilic films produced by
      hot-melt extrusion.
AB  - Films containing hydroxypropylcellulose (HPC) and polyethylene oxide (PEO) were
      prepared using a Randcastle extruder (Model 750) with and without Vitamin E TPGS
      (TPGS, D-alpha-tocopheryl polyethylene glycol 1000 succinate) as an additive.
      Conventional plasticizers including polyethylene glycol 400 (PEG 400), triethyl
      citrate (TEC), and acetyltributyl citrate (ATBC) were also incorporated into
      films containing a 50:50 blend of HPC and PEO. The physical-mechanical properties
      including tensile strength (TS) and percent elongation (%E) were determined on an
      Instron according to the ASTM standards. Glass transition temperatures (T(g)) of
      the extruded films were determined utilizing a DSC 2920 Modulated differential
      scanning calorimeter and THERMAL ANALYST 2000 software. Gel permeation
      chromatography was used to study the stability of the polymer films under the
      processing conditions. The addition of 1, 3, and 5% Vitamin E TPGS, respectively,
      decreased the glass transition temperature of the extruded films containing
      either a 50:50 or 80:20 ratio of HPC to PEO in an almost linear fashion. In
      addition, the presence of 3% Vitamin E TPGS lowered the T(g) over 11 degrees C
      when compared with the HPC/PEO 50:50 blend film without TPGS, thus functioning as
      a plasticizer. The tensile strength decreased with increasing concentrations of
      TPGS, and the %E increased over 3-fold when compared with the HPC/PEO film that
      contained no additives. The film containing 3% Vitamin E TPGS had a similar
      tensile strength to that of the films containing 3% PEG 400, and a 3-fold
      increase in percent elongation when compared with the films containing 3% TEC and
      3% ATBC. In addition, the Vitamin E TPGS facilitated the processing of the
      HPC/PEO films by decreasing the barrel pressure, drive amps, and torque of the
      extruder equipment.

PMID- 10915928
TI  - Calorimetry a method to be used to characterise pyrolytically decarboxylated
      bicarbonate and assess its stability at elevated humidities.
AB  - Microcalorimetry was used to characterise bicarbonate after treatment at high
      temperatures. By measuring the heat flow from a sample of bicarbonate at 100%
      relative humidity, the net exothermic contribution could be used to estimate the
      fraction of pyrolytically formed Na(2)CO(3). The enthalpy value corresponding to
      the heat of solution of Na(2)CO(3) was also applicable to a physical mixture of
      NaHCO(3)/Na(2)CO(3). However, from the characteristic peaks of the heat flow
      versus time curve, pyrolytically formed Na(2)CO(3) could be distinguished from
      that present in the physical mixture. The different bicarbonate batches of
      varying degree of pyrolytic decarboxylation were also observed at an elevated
      relative humidity of 54%. From these measurements it could be inferred that a
      decarboxylation of up to 4.5% could be allowed without any significant effect on
      the stability of bicarbonate at 54%.

PMID- 10915929
TI  - Synthesis, pharmacokinetics and anticonvulsant activity of 7-chlorokynurenic acid
      prodrugs.
AB  - 7-Chlorokynurenic acid 1 is a potent glycine-N-methyl-D-aspartate (NMDA) receptor
      antagonist, but it shows weak activity after systemic administration. In order to
      overcome the Blood-brain barrier (BBB), we synthetized three new esters 2-4 of 1
      obtained by chemical conjugation with essential nutrients such as glucose and
      galactose, that are actively transported across the BBB. These compounds were
      assayed to evaluate their in vitro chemical and enzymatic hydrolysis. In addition
      the prodrugs 2-4 were tested for their ability to protect mice against NMDA
      induced seizures after systemic administration. All the prodrugs 2-4 appeared
      moderately stable in pH 7.4 buffered solution and were susceptible to in vitro
      enzymatic hydrolysis. Intraperitoneal administration of either esters 2 or 4 was
      highly protective against seizures induced by NMDA in mice, with the latter
      prodrug showing the highest anticonvulsive activity. In addition, ester 4
      undergoes a time-dependent extracellular hydrolysis into 1 when applied to mixed
      cultures of mouse cortical cells, a model that reproduces in vitro the cellular
      milieu encountered by the prodrugs once they penetrate the brain parenchyma.

PMID- 10915930
TI  - Pharmacokinetics and absolute bioavailability of oral cefuroxime axetil in the
      rat.
AB  - The objectives of this study were to determine the oral bioavailability of
      cefuroxime (C) and to evaluate the pharmacokinetic model that best describes the
      plasma concentration behaviour following single intravenous (IV), intraperitoneal
      (IP) and oral single doses. The same dose of C was administered by IV, IP and
      oral routes to three separate groups of rats (2.02 mg of cefuroxime axetil (CA)
      by the oral route or 1.78 mg of cefuroxime sodium (CNa) by IV and IP route). A
      two-compartment open model without lag time can predict the C disposition
      kinetics. The influence of the administration route on the pharmacokinetic
      parameters and AUC values was investigated by means of a one-way analysis of
      variance test. The results indicated that the first-pass effect in the intestine
      and liver reduce oral bioavailability when the drug is administered orally.
      Cefuroxime bioavailability after oral and IP administration estimated from the
      plasma levels was nearly 24 and 75%, respectively.

PMID- 10915931
TI  - Pharmacokinetics of metoprolol enantiomers following single and multiple
      administration of racemate in rat.
AB  - The chiral beta-adrenergic blocking agent metoprolol (MET), which is marketed as
      a racemate, is a highly extracted drug with rapid absorption. The enantiomeric
      disposition of MET is reported following racemic administration as a single and
      as multiple oral dosing four times per day for four days in male Sprague-Dawley
      rats (n=6 in each group). Plasma was collected and enantiomeric concentrations of
      MET were determined using a stereospecific HPLC assay. The R/S ratio for AUC is
      not statistically different from unity either after single or after multiple
      administration of racemate. The oral clearance after single dose was 1.99+/-0.87
      and 2. 26+/-0.85 ml min(-1) kg(-1) for R- and S-MET, respectively. These values
      were decreased to 0.59+/-0.21 and 0.64+/-0.26 ml min(-1) kg(-1) after multiple
      administration of racemate. The corresponding values for the elimination half
      lives were approximately 35 and 33 min after single and multiple dose
      administration for both enantiomers, respectively. These results may suggest a
      saturable first pass metabolism of MET as its enantiomers are accumulated in
      plasma following multiple dosing in the rat model.

PMID- 10915932
TI  - Polyoxyethylene-poly(methacrylic acid-co-methyl methacrylate) compounds for site
      specific peroral delivery.
AB  - pH-sensitive interpolymer interactions between high molecular weight
      polyoxyethylene (POE) and poly(methacrylic acid-co-methyl methacrylate) (Eudragit
      (EUD) L100 or S100) are evidenced and exploited to prepare, from either POE-EUD
      coevaporates or POE+EUD physical mixtures, both in the 1:1 wt. ratio, compressed
      matrix tablets, potentially able to deliver the model drug, prednisolone, to
      sites in the GI tract characterized by specific pHs, such as the jejunum or the
      ileum. With these devices, drug release is inhibited at pHs lower than the
      threshold of EUD ionization, whereas at pHs exceeding such a threshold, the
      matrix undergoes a gradual erosion, which controls the release. A post
      compression exposure of tablets to the vapors of appropriate solvents realizes
      the necessary compaction of matrices, in fact, a high compression force (3 ton)
      is insufficient, per se, to prevent matrix disintegration in the dissolution
      medium, whereas such a disintegration is prevented by the treatment with solvent
      vapors, even with a low compression force (0.3 ton). With the POE+EUD physical
      mixtures, the exposure to solvent vapors promotes the formation of a layer of POE
      EUD complex at the interfaces of the POE and EUD particles in matrix, which
      inhibits release at pHs lower than that designed for delivery. Both POE and EUD
      concur to determine the properties of the POE-EUD complex relevant to drug
      release, indeed, EUD ionization, which elicits matrix erosion and drug release,
      is favored by the hydrophilic POE. In fact, matrices based on plain EUD exhibit a
      comparatively low release rate, more suited to an extended delivery to the colon
      than to a specific delivery to the ileum. Details of the release mechanism are
      discussed.

PMID- 10915933
TI  - Selective determination of pyridoxine in the presence of hydrosoluble vitamins
      using a continuous-flow solid phase sensing device with UV detection.
AB  - A very simple, inexpensive and highly selective flow injection UV
      spectrophotometric method for the determination of vitamin B(6) is presented. The
      native absorbance of the analyte is continuously monitored at 290 nm when it is
      transiently retained on Sephadex SP C-25 cation exchanger gel beads placed in the
      detection area of a flow cell. The preconcentration on the active solid phase
      provides by itself a high increase in sensitivity compared with the same
      procedure carried out without a solid support. The analytical response is linear
      in the concentration ranges 1-10 and 2-20 microg ml(-1) using 600 and 1250 microl
      of sample, respectively. The R.S.D. (%) are 0.65 (600 microl) and 0.84 (1250
      microl) and the detection limits 0.08 and 0.02 microg ml(-1), respectively. The
      procedure was successfully applied to the determination of vitamin B(6) in
      pharmaceuticals containing (among other active principles) hydrosoluble vitamins
      in much higher concentrations than that tolerated by the method if performed in
      aqueous solution. Nevertheless they were tolerated using the proposed sensor due
      to the selective retention of the analyte.

PMID- 10915934
TI  - Enhanced transdermal delivery of tetracaine by electroporation.
AB  - The effect of electroporation on the transport of tetracaine through skin in
      vitro was studied using side-by-side compartment diffusion cells method. After
      achieving steady state by passive diffusion, fluxes of tetracaine achieved with
      passive diffusion, electroporative pulse and iontophoresis were compared.
      Electroporation (square-wave pulse, voltage 130 V, pulse time 0.4 s, pulse
      frequency 40 pulses min(-1)) or iontophoresis (0.2.mA cm(-2), lasting for 4 h)
      increased the transport of tetracaine through skin. The flux of tetracaine at
      0.25 h after electroporation (pulse number 400) was 54.6+/-6.0 microg.cm(-2).h(
      1), that after iontophoresis was 17.4+/-5.8 microg.cm(-2).h(-1) and that after
      passive diffusion was 8.2+/-0.5 microg.cm(-2).h(-1). In addition, the fluxes of
      tetracaine increased with the increasing of pulse number. From these results, it
      is clear that electroporation is effective in enhancing transdermal delivery of
      tetracaine and its function is better than iontophoresis.

PMID- 10915935
TI  - Intranasal bioavailability of apomorphine from carboxymethylcellulose-based drug
      delivery systems.
AB  - Carboxymethyl cellulose (CMC) powder formulation of apomorphine was prepared by
      lyophilization and characterized with respect to the in vitro and intranasal in
      vivo release of apomorphine in rabbits. This was compared to apomorphine release
      from degradable starch microspheres (DSM) and lactose, as well as in vivo
      absorption after subcutaneous injection. In vitro apomorphine release from CMC
      was sustained, unlike that of DSM and lactose. Changing the drug loading of CMC
      from 15 to 30% (w/w) influenced drug release rate, which increased with increased
      drug loading. In vivo absorption of apomorphine from lactose, DSM and
      subcutaneous injection were rapid and not sustained. Slower absorption rates of
      apomorphine occurred from CMC. The fastest absorption rate was obtained with
      lactose and the slowest with CMC of 15% (w/w) drug loading. The T(max) from the
      CMC dosage forms were significantly prolonged compared to the immediate release
      forms. Plasma drug levels were sustained with CMC. The plasma concentration was
      maintained within 50% of the C(max), longer (15% (w/w), 70 min; 30% (w/w), 40
      min) compared to the rest (lactose, 20 min; DSM, 25 min, subcutaneous injection,
      35 min). The sustained plasma level of apomorphine by CMC was achieved with
      relative bioavailabilities equivalent to subcutaneous injection.

PMID- 10915936
TI  - Comparative enhancer effects of Span20 with Tween20 and Azone on the in vitro
      percutaneous penetration of compounds with different lipophilicities.
AB  - Sorbitan monolaurate (Span20) was used in this study to analyze the influence of
      the polar functional group on the effects that non-ionic surfactants have on skin
      permeability. Its ethoxylate derivative polysorbate 20 (Tween20) and Azone, both
      with the same C12 alkyl chain as Span20, were used for comparative purposes. We
      evaluated the relative potency of the three molecules as enhancers in the
      permeability of a series of compounds with lipophilicities ranging from log Poct=
      0.95 to log Poct=2.33. The influence of the enhancer concentration was also
      studied. For this purpose the epidermis of Wistar rat was pretreated with
      ethanolic solutions (1 and 5%, w/v) of each enhancer. Our results indicate that
      the nature of the enhancer head group greatly influences cutaneous barrier
      impairment. The enhancer concentration must also be taken into account, even
      though the influence of the concentration seems to depend on the lipophilicity of
      the penetrant assayed.

PMID- 10915937
TI  - Characterisation of instantaneous water absorption properties of pharmaceutical
      excipients.
AB  - Powders absorb water by both capillary imbibition and swelling. The capillary
      process is almost instantaneous but swelling occurs over a period of time. An
      isothermal transient ionic current technique was used in this study to
      characterise the instantaneous absorption properties (rate and capacity) of a few
      selected pharmaceutical excipients. The results indicate that the instantaneous
      and long term water absorption properties of pharmaceutical powders can differ
      considerably. The rate of instantaneous water absorption appears to correlate
      with the total surface area while the absorption capacity correlates more with
      the porosity of the powder.

PMID- 10915938
TI  - Specific gene transfer mediated by galactosylated poly-L-lysine into hepatoma
      cells.
AB  - Plasmid DNA/galactosylated poly-L-lysine(GalPLL) complex was used to transfer
      luciferase reporter gene in vitro into human hepatoma cells by a receptor
      mediated endocytosis process. DNA was combined with galPLL via charge interaction
      (DNA:GalPLL:fusogenic peptide, 1:0.4:5, w/w/w) and the resulting complex was
      characterized by dynamic light scattering, gel retardation assay and zeta
      potential analyzer to determine the particle size, electrostatic charge
      interaction, and apparent surface charge. The complex was tested for the
      efficiency of gene transfer in cultured human hepatoblastoma cell line Hep G2 and
      fibroblast cells NIH/3T3 in vitro. The mean diameter of the complex
      (DNA:GalPLL=1:0.4, w/w) was 256+/-34.8 nm, and at this ratio, it was positively
      charged (zeta potential of this complex was 10.1 mV). Hep G2 cells, which express
      a galactose specific membrane lectin, were efficiently and selectively
      transfected with the RSV Luc/GalPLL complex in a sugar-dependent manner. NIH/3T3
      cells, which do not express the galactose-specific membrane lectin, showed only a
      marginal level of gene expression. The transfection efficiency of GalPLL
      conjugated DNA complex into Hep G2 cells was greatly enhanced in the presence of
      fusogenic peptide that can disrupt endosomes, where the GalPLL-DNA complex is
      entrapped with the fusogenic peptide. With the fusogenic peptide KALA, the
      luciferase activity in Hep G2 cells was ten-fold higher than that of cells
      transfected in the absence of the fusogenic peptide. Our gene transfer
      formulation may find potential application for the gene therapy of liver
      diseases.

PMID- 10915939
TI  - Increased partitioning of pilocarpine to the oily phase of submicron emulsion
      does not result in improved ocular bioavailability.
AB  - Submicron emulsions containing pilocarpine as ion-pair with mono
      dodecylphosphoric acid were prepared. Physical stability of these preparations
      was confirmed during 4 months of storage at 4 degrees C. Approximately 50% of the
      drug was found in the aqueous phase of emulsion separated using an
      ultrafiltration technique, while the rest was present in the oily phase and
      interphase. The miotic effect observed in rabbits after application of the ion
      pair in aqueous solution or in submicron emulsion was the same; indicating that
      the drug distribution into the oily phase of the colloidal vehicle does not
      improve ocular bioavailability.

PMID- 10915940
TI  - Oral bioavailability and hypoglycaemic activity of tolbutamide/cyclodextrin
      inclusion complexes.
AB  - The purpose of the present study was to evaluate the enhancement of tolbutamide
      (TBM) oral bioavailability and hypoglycaemic activity through complexation with
      beta-cyclodextrin (beta-CD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD). TBM
      and its freeze-dried inclusion complexes were administered to rabbits (New
      zealand breed; n=6), in a dose of 20 mg/kg. TMB plasma levels were measured by
      HPLC and glucose levels were analysed according to Trinder (Trinder, P., 1969.
      Determination of glucose in blood using glucose oxidase with an alternative
      oxygen acceptor. Ann. Clin. Biochem. 6, 24-28). The pure drug attained a maximum
      of plasma concentration (C(max)) of 18.58+/-3.27 microg/ml at 8.5 h (T(max)),
      whereas with inclusion complexes, C(max) increased about two times and appeared
      at ca. 4 h. AUC(0-24) of complexes was about 1.6 times as much as that of the
      pure drug. Thus, the extent of oral absorption of TBM from inclusion complexes
      was significantly greater and faster when compared with drug alone. In addition,
      without cyclodextrins the maximum hypoglycaemic effect (CVG(max)) of TBM (34. 1%)
      was observed at 5.6 h (Tg(max)). CVG(max) of TBM/beta-CD and TBM/HP-beta-CD
      inclusion complexes were 34.1% (at 6.5 h) and 37.7% (at 5.1 h), respectively.
      AAC(0-24) of inclusion complexes was 1.4 times larger than that of pure drug.
      Hence, the oral administration of complexed TBM not only improved the drug
      absorption, but also the TBM hypoglycaemic activity.

PMID- 10915942
TI  - Prevention of protein adsorption by flexible and rigid chain molecules.
AB  - The ability of tethered polymer layers to reduce the non-specific adsorption of
      proteins is studied using a molecular theory. The protein adsorption isotherms
      are calculated for flexible and rigid molecules as well as for mixtures. It is
      found, in agreement with earlier predictions, that flexible polymers are more
      effective in preventing protein adsorption. The interactions of the polymer with
      the surface are shown to be very important in determining the ability of the
      polymer layer to reduce the adsorption of proteins. Further, it is found that one
      can tune the adsorption of a certain protein conformation by changing the
      interactions between the surface and the polymer segments or the composition in
      the case of mixtures. It is found that the optimal layers to obtain large
      reduction of protein adsorption and availability of functional groups for binding
      are obtained by using mixtures of flexible and rod-like molecules. The role of
      the polymer-surface interactions is shown to be different for the kinetic control
      of protein adsorption as compared to thermodynamic control. The application of
      the findings as guidelines for the molecular design of biocompatible materials is
      discussed.

PMID- 10915941
TI  - Effect of hydroxypropylmethylcellulose (HPMC) on the release profiles and
      bioavailability of a poorly water-soluble drug from tablets prepared using
      macrogol and HPMC.
AB  - The aim of the present study was to investigate the effect of
      hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled
      release of drug, on the release profiles and bioavailability of the poorly water
      soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and
      HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG
      HPMC tablet) was markedly increased with increasing compression force used during
      the preparation from 20 to 200 MPa. The values reached their maximal levels
      (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at
      the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it
      was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the
      improvement of its dissolution rate in the presence of PEG. NP dissolution was
      complete at the latest within 1 h. On the other hand, dissolution of NP from the
      NP-PEG-HPMC tablet was significantly delayed with an increase in the
      concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC
      tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC
      also increased. Interestingly, the same peak plasma NP concentration (C(max)) and
      the area under the plasma NP concentration-time curve (AUC(0-10)) were observed
      for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max)
      (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC
      tablet was orally administered to rabbits. We describe here a preparation method
      of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules
      (prepared with PEG) and HPMC.

PMID- 10915943
TI  - PEG-covered lipid surfaces: bilayers and monolayers.
AB  - In this review paper we survey the ways in which various micropipet techniques
      have been used to study the mechanochemical and interactive features of lipid
      bilayer vesicles and monolayer-coated gas bubbles. Special emphasis will be made
      on characterizing the barrier properties of grafted PEG layers and how a
      hierarchical approach that uses a short barrier and extended ligand allows us to
      start to mimic nature's own solution to the problem of ubiquitous repulsion and
      specific attraction. The information gained from such studies not only
      characterizes the membrane and other lipid surfaces and their intersurface
      interactions from a fundamental materials science perspective, but also provides
      essential materials property data that are required for the successful design and
      deployment of lipid-based carriers and other capsules in applications involving
      this so-called 'stealthy' surface.

PMID- 10915944
TI  - Methods for reducing biosensor membrane biofouling.
AB  - The deleterious effect that biofouling has on sensor stability is a serious
      impediment to the development of long term implanted biosensors. This paper
      reviews the surface modification strategies currently employed to minimize
      membrane biofouling of in vivo sensors. Nine sensor modifications are discussed
      herein: hydrogels, phospholipid-based biomimicry, flow-based systems, Nafion,
      surfactants, naturally derived materials, covalent attachments, diamond-like
      carbons, and topology.

PMID- 10915945
TI  - Method of immobilization of carboxymethyl-dextran affects resistance to tissue
      and cell colonization.
AB  - Coatings from carboxymethylated dextrans (CMDs) were fabricated, analyzed by XPS,
      and investigated for their ability to inhibit corneal epithelial tissue outgrowth
      and bovine corneal epithelial cell attachment and growth. CMDs with differing
      degrees of carboxymethyl substitution and various molecular weights were
      synthesized by the solution reaction of dextrans with bromoacetic acid under
      different reactant ratios. The CMD compounds thus obtained were attached onto
      aminated surfaces produced in two ways: by the plasma deposition of a coating
      from n-heptylamine vapour, and by the plasma deposition of an acetaldehyde
      coating onto whose surface aldehyde groups the polyamine compounds polylysine,
      polyethyleneimine and polyallylamine were immobilized to provide platforms for
      CMD immobilization. XPS spectra showed that the latter route produced thicker
      coatings than the former approach. CMD molecules attached directly onto the
      plasma-fabricated amine surface supported some tissue migration; the extent of
      carboxymethyl substitution and the molecular weight of the CMDs had little
      influence. For CMDs immobilized via polyamine spacers, on the other hand, tissue
      outgrowth was completely inhibited, and again there were no discernible effects
      from the extent of carboxymethyl substitution and the molecular weight of the
      CMDs. In assays involving cell attachment and growth, analogous observations were
      found. Thus, the mode of immobilization of these polysaccharide coatings is the
      dominant factor in their anti-fouling performance, suggesting that optimization
      of the architecture of polysaccharide coatings may be an important factor for
      maximizing their cell-repellent abilities.

PMID- 10915946
TI  - Non-fouling surfaces produced by gas phase pulsed plasma polymerization of an
      ultra low molecular weight ethylene oxide containing monomer.
AB  - The pulsed plasma polymerization of low molecular weight molecules containing
      only one (ethylene oxide vinyl ether) and two (diethylene oxide vinyl ether)
      ethylene oxide units were investigated. The surface density of EO units retained
      in the polymer films increases sharply with decreasing average power input during
      deposition, particularly at very low plasma duty cycles. The protein adsorption
      properties of these plasma synthesized polymer were investigated using 125I
      labeled albumin and fibrinogen. Surprisingly effective, non-fouling surfaces were
      observed with films synthesized from the monomer containing two ethylene oxide
      units; however, the monomer containing only one EO unit gave surfaces that were
      not particularly effective in preventing protein adsorptions. The results
      obtained show that ultra short chain length PEO modified surfaces can be
      biologically non-fouling. This, in turn, has interesting consequences in terms of
      trying to identify the basic reason for the effectiveness of EO units in
      preventing biomolecule adsorptions on surfaces.

PMID- 10915947
TI  - Force measurements on cell repellant and cell adhesive alginic acid coated
      surfaces.
AB  - The atomic force microscope (AFM) was used to acquire force versus distance
      curves between the cantilever tip and samples bearing a surface overlayer of
      covalently linked alginic acid. The alginic acid coating resists cell-adhesion in
      in vitro experiments involving a normal and a tumor cell line. However, the
      surface becomes cell adhesive when alginic acid coated samples are subjected to
      glow discharge treatment. Force curves show in both cases the typical features
      resulting from the interaction between the cantilever tip and a hydrophilic,
      compressible polymer overlayer, suggesting that in both cases a diffuse interface
      with water exists. Following some recent findings on oligoethyleneglycol
      terminated self-assembled-monolayers, it is suggested that conformational and
      molecular aspects of hydrophilic surface layers, rather than steric repulsion
      effects, could play a significant role in the mechanism that controls resistance
      to bio-adhesion.

PMID- 10915948
TI  - Phosphorylcholine-based polymers and their use in the prevention of biofouling.
AB  - This article provides an overview of work carried out on the synthesis and non
      fouling properties of phosphorylcholine (PC)-containing polymers. The concept of
      biomimicry is outlined and the major classes of synthetic PC-based materials
      described. Studies on the interaction of these materials with various proteins
      are collated and the mechanism for their protein-resistant nature is discussed.
      Similarly, cellular interactions are also reviewed, with ex-vivo and in-vivo
      clinical data provided to demonstrate the usefulness of these materials for
      improving the properties of medical devices.

PMID- 10915949
TI  - Immobilization of trypsin on porous glycidyl methacrylate beads: effects of
      polymer hydrophilization.
AB  - The immobilization of trypsin at porous glycidyl methacrylate (GMA-GDMA) beads
      was investigated. In particular, the effects of surface modification of the beads
      through hydrophilic polymers on the amount protein immobilized and on the extent
      of retained activity after immobilization were adressed. Furthermore,
      immobilization at unmodified and hydrophilized beads from aqueous solution was
      compared to that from a water-in-oil microemulsion. It was found that the amount
      trypsin immobilized at the unmodified GMA-GDMA beads was significantly higher
      than that at hydrophilized GMA-GDMA beads. However, also the extent of specific
      activity loss after immobilization was larger for the unmodified than for the
      hydrophilized beads. Despite the latter, however, the total activity displayed by
      the hydrophilized beads was comparable to the unmodified beads at best. On the
      other hand, by peforming the immobilization from the microemulsion a high
      immobilization yield can be reached even for the hydrophilized beads, which also
      results in a higher degree of retained activity in the latter case than obtained
      for immobilization at the unmodified beads. Using this approach therefore
      resulted in the highest total activity of the trypsin-activated GMA-GDMA beads.

PMID- 10915950
TI  - Study of complement activation on well-defined surfaces using surface plasmon
      resonance.
AB  - It has been accepted that covalent immobilization of C3b on artificial materials
      is the most important step to initiate the complement activation. However, there
      are few studies that have directly demonstrated covalent immobilization of C3b on
      artificial surfaces. In this study, model thin layers were prepared by the self
      assembled monolayer method to produce a surface covered with hydroxyl or methyl
      groups using mercaptododecane (CH(3)-SAM) and mercaptoundecanol (OH-SAM).
      Interactions of the complement system with the model surfaces were studied using
      a surface plasmon resonance instrument. The OH-SAM immobilized C3b, resulting in
      activating of the complement system through the alternative pathway in Veronal
      buffered saline, but this surface did not activate the classical pathway.
      However, the OH-SAM could not activate the alternative pathway in Veronal
      buffered saline containing 10 mM EGTA and 2 mM MgCl(2) that is believed not to
      interfere with the activation of the alternative pathway. The hydrophobic CH(3)
      SAM surface could not activate the classical pathway, but activated the
      alternative pathway, although the extent was small.

PMID- 10915951
TI  - Long-circulating gadolinium-loaded liposomes: potential use for magnetic
      resonance imaging of the blood pool.
AB  - In our previous paper, we reported a method of liposome loading with Gadolinium
      (Gd) via so called polychelating amphiphilic polymer (PAP). A novel Gd-containing
      polymeric probe, suitable for the incorporation into the liposomal membrane, was
      prepared from a low-molecular-weight DTPA-polylysine by linking its N-terminus to
      a lipid anchor, NGPE-PE. When compared with known membranotropic MR probes, such
      as Gd-DTPA-SA and Gd-DTPA-PE, liposomes containing new membrane-bound
      polychelator possess enhanced relaxivity for water protons resulting in an
      increase of tissue signal intensity on MR images. In this study, we developed the
      optimized protocol to prepare a liposomal MR contrast agent with high relaxivity
      and narrow size distribution. Gd-containing liposomes were additionally modified
      with PEG to provide longevity in vivo. We also demonstrated that upon intravenous
      administration in rabbit and dog, the new preparation causes a prolonged decrease
      in the blood T(1) value (reflecting the proton relaxation rate in the blood) and
      may be considered as a potential contrast agent for MRI of the blood pool.

PMID- 10915952
TI  - 'Stealth' corona-core nanoparticles surface modified by polyethylene glycol
      (PEG): influences of the corona (PEG chain length and surface density) and of the
      core composition on phagocytic uptake and plasma protein adsorption.
AB  - Nanoparticles possessing poly(ethylene glycol) (PEG) chains on their surface have
      been described as blood persistent drug delivery system with potential
      applications for intravenous drug administration. Considering the importance of
      protein interactions with injected colloidal dug carriers with regard to their in
      vivo fate, we analysed plasma protein adsorption onto biodegradable PEG-coated
      poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(varepsilon
      caprolactone) (PCL) nanoparticles employing two-dimensional gel electrophoresis
      (2-D PAGE). A series of corona/core nanoparticles of sizes 160-270 nm were
      prepared from diblock PEG-PLA, PEG-PLGA and PEG-PCL and from PEG-PLA:PLA blends.
      The PEG Mw was varied from 2000-20000 g/mole and the particles were prepared
      using different PEG contents. It was thus possible to study the influence of the
      PEG corona thickness and density, as well as the influence of the nature of the
      core (PLA, PLGA or PCL), on the competitive plasma protein adsorption, zeta
      potential and particle uptake by polymorphonuclear (PMN) cells. 2-D PAGE studies
      showed that plasma protein adsorption on PEG-coated PLA nanospheres strongly
      depends on the PEG molecular weight (Mw) (i.e. PEG chain length at the particle
      surface) as well as on the PEG content in the particles (i.e. PEG chain density
      at the surface of the particles). Whatever the thickness or the density of the
      corona, the qualitative composition of the plasma protein adsorption patterns was
      very similar, showing that adsorption was governed by interaction with a PLA
      surface protected more or less by PEG chains. The main spots on the gels were
      albumin, fibrinogen, IgG, Ig light chains, and the apolipoproteins apoA-I and
      apoE. For particles made of PEG-PLA45K with different PEG Mw, a maximal reduction
      in protein adsorption was found for a PEG Mw of 5000 g/mole. For nanospheres
      differing in their PEG content from 0.5 to 20 wt %, a PEG content between 2 and 5
      wt % was determined as a threshold value for optimal protein resistance. When
      increasing the PEG content in the nanoparticles above 5 wt % no further reduction
      in protein adsorption was achieved. Phagocytosis by PMN studied using
      chemiluminescence and zeta potential data agreed well with these findings: the
      same PEG surface density threshold was found to ensure simultaneously efficient
      steric stabilization and to avoid the uptake by PMN cells. Supposing all the PEG
      chains migrate to the surface, this would correspond to a distance of about 1.5
      nm between two terminally attached PEG chains in the covering 'brush'. Particles
      from PEG5K-PLA45K, PEG5K-PLGA45K and PEG5K-PCL45K copolymers enabled to study the
      influence of the core on plasma protein adsorption, all other parameters (corona
      thickness and density) being kept constant. Adsorption patterns were in good
      qualitative agreement with each other. Only a few protein species were
      exclusively present just on one type of nanoparticle. However, the extent of
      proteins adsorbed differed in a large extent from one particle to another. In
      vivo studies could help elucidating the role of the type and amount of proteins
      adsorbed on the fate of the nanoparticles after intraveinous administration, as a
      function of the nature of their core. These results could be useful in the design
      of long circulating intravenously injectable biodegradable drug carriers endowed
      with protein resistant properties and low phagocytic uptake.

PMID- 10915953
TI  - The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA
      nanoparticles following oral administration.
AB  - The aim of the present work was to evaluate if the presence of a
      polyethylenglycol (PEG) coating around PLA nanoparticles would affect their
      interaction with biological surfaces, following oral administration to rats. For
      this purpose, a model antigen, 125I-radiolabeled tetanus toxoid, was encapsulated
      in PLA and PLA-PEG nanoparticles by a modified water-in-oil-in-water solvent
      evaporation technique. Firstly, the stability of the nanoparticles in simulated
      gastrointestinal fluids was evaluated. Results showed an interaction between the
      nanoparticles and the enzymes of the digestive fluids, this interaction being
      considerably reduced by the PEG coating around the particles. On the other hand,
      the PLA forming the nanoparticles was found to be only slightly degraded (9%
      converted to lactate for PLA nanoparticles and 3% for PLA-PEG nanoparticles) and
      that the encapsulated tetanus toxoid remained mostly associated to the
      nanoparticles upon incubation in the digestive fluids for up to 4 h. Finally, the
      in vivo experiments showed that, after oral administration to rats, the levels of
      encapsulated radioactive antigen in the blood stream and lymphatics were higher
      for PLA-PEG nanoparticles than for PLA nanoparticles. In conclusion, the PLA-PEG
      nanoparticles have a promising future as protein delivery systems for oral
      administration.

PMID- 10915954
TI  - Photoinduced graft polymerization of 2-methacryloyloxyethyl phosphorylcholine on
      polyethylene membrane surface for obtaining blood cell adhesion resistance.
AB  - Phospholipid polymer, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], was
      grafted with polyethylene (PE) membrane using photoinduced polymerization
      technique to make the membrane resistant to cell adhesion. The water contact
      angle on the PE membrane grafted with poly(MPC) decreased with an increase in the
      photopolymerization time. This decrease corresponded to the increase in the
      amount of poly(MPC) grafted on the PE surface. The same graft polymerization
      procedure was applied using other hydrophilic monomers, such as acrylamide (AAm),
      N-vinylpyrrolidone (VPy) and methacryloyl poly(ethylene glycol) (MPEG). These
      monomers were also polymerized to form grafted chains on the PE membrane, and the
      grafting was confirmed with X-ray photoelectron spectroscopy. Analysis of amount
      and distribution of plasma proteins at the plasma-contacting surface of the
      original and the modified PE membranes were analyzed using immunogold assay. The
      grafting of poly(MPC) and poly(VPy) on PE membrane reduced the plasma protein
      adsorption significantly compared with that on the original PE membrane. However,
      the PE membranes grafted with poly(AAm) or poly(MPEG) did not show any effects on
      protein adsorption. Platelet adhesion on the original and modified PE membranes
      from platelet-rich plasma was also examined. A large number of platelets adhered
      and activated on the original PE membrane. Grafting with poly(AAm) did not
      suppress platelet adhesion, but grafting with poly(MPC) or poly(VPy) on the PE
      membrane was effective in preventing platelet adhesion. It is concluded that the
      introduction of the phosphorylcholine group on the surface could decrease the
      cell adhesion to substrate polymer.

PMID- 10915955
TI  - Preparation of non-fouling surface through the coating with core-polymerized
      block copolymer micelles having aldehyde-ended PEG shell.
AB  - A new type of surface modification with reactive polymeric micelle was carried
      out for the creation of non-fouling surface. Amphiphilic poly(ethylene glycol)-b
      poly(D,L lactide) (PEG/PLA) copolymers possessing acetal group at PEG-end and
      methacryloyl group at PLA-end were quantitatively synthesized via an anionic
      polymerization technique. A micelle of narrow distribution was prepared from the
      block copolymer. Acetal groups on the micelle surface were quantitatively
      converted into aldehyde group by an acid treatment. The methacryloyl group
      located in the core of the micelle was polymerized via radical polymerization to
      form core-polymerized micelle having reactive aldehyde groups on the surface. The
      core-polymerized reactive micelle was coated to a primary amino-containing
      polypropylene (PP) plate that was prepared by a plasma treatment. A reductive
      amination reaction was employed for a conjugation of the reactive core
      polymerized micelle on the surface via a covalent linkage. The coating was
      evaluated by X-ray photoelectron spectroscopy, zeta-potential measurement, and
      the adsorption of bovine serum albumin, and compared with the PEG-coating under
      the same condition. The ratio of peak from &Cmacr;&z.sbnd;O bond to
      C&z.sbnd;&Cmacr;&z.sbnd;C bond indicated that the density of PEG on the surface
      was higher for the micelle coating than the linear PEG-coating. This is also
      confirmed by the zeta-potential measurement. By coating the amino-PP surface with
      micelle, the zeta-potential was remarkably decreased while the PEG-coating under
      the same condition decreased only appreciably, indicating that micelle coating
      efficiently masked the surface charge. Further, micelle-covered surface exhibited
      reduction of protein adsorption. The reduction of protein adsorption along with
      remarkably masked surface charge implies the high applicability of the micelle
      coatings to biomedical and bioanalytical applications.

PMID- 10915956
TI  - Surface modification of polyethylene terephthalate using PEO-polybutadiene-PEO
      triblock copolymers.
AB  - The initial step of thrombus formation on blood-contacting biomaterials is known
      to be adsorption of blood proteins followed by platelet adhesion. It is generally
      accepted that surface modification of the biomaterials with poly(ethylene oxide)
      (PEO) substantially reduces protein adsorption and cell adhesion. Dacron(R)
      (polyethylene terephthalate) fabric, which is one of the biomaterials commonly
      used in blood-contacting devices, was grafted with PEO. A simple two-step
      procedure for covalent grafting of PEO onto the surface of Dacron(R) fabric was
      used. The surface was first treated with PEO-polybutadiene-PEO (PEO-PB-PEO)
      triblock copolymer, to introduce a layer of double bonds onto the surface. The
      Dacron(R) surface was then exposed to a solution of Pluronic(R) F108 (PF108), a
      commercially available PEO-poly(propylene oxide)-PEO (PEO-PPO-PEO) triblock
      copolymer. The surface with two adsorbed layers of PEO-PB-PEO and PF108 was gamma
      irradiated in the presence of PF108 in the bulk solution for a total radiation
      dose of 0.8 Mrad. The bulk concentrations of PEO-PB-PEO and PF108 were varied to
      maximize the efficiency of PEO grafting. Fibrinogen adsorption on PEO-grafted
      surfaces was reduced more than 90%, compared with that on control surfaces,
      irrespective of the bulk concentrations of polymers used for grafting. Platelet
      adhesion was also reduced substantially by PEO grafting. Only a few round
      platelets were able to adhere to the PEO-grafted surface, while the control
      surface was fully covered with aggregates of activated platelets. PEO grafting on
      polyethylene terephthalate using PEO-PB-PEO and PEO-PPO-PEO block copolymers is a
      simple approach that can be used for various other biomaterials.

PMID- 10915957
TI  - Platelet and bacterial repellence on sulfonated poly(ethylene glycol)-acrylate
      copolymer surfaces.
AB  - Novel poly(ethylene glycol) (PEG) and sulfonated PEG (PEG-SO(3)) acrylate
      copolymers have been prepared and characterized to apply as coating and blending
      materials for biomedical applications. The modified surfaces using acrylate
      copolymers demonstrated increased hydrophilicity, possibly due to the
      hypothesized reorientation of PEG/PEG-SO(3) chains into water phase. All
      copolymer surfaces demonstrated less platelet adhesion than control. In addition,
      platelet adhesion on copolymer surfaces decreased as the chain length of PEG and
      sulfonated PEG in copolymers increases. All copolymer surfaces reduced bacterial
      adhesion significantly and the adhesion level differs depending on surfaces as
      well as media. The obtained results attest to the usefulness of these copolymers
      as a coating or additive material to improve the blood compatibility of blood
      contacting devices.

PMID- 10915958
TI  - Synthesis, characterization and protein adsorption behaviors of PLGA/PEG di-block
      co-polymer blend films.
AB  - A series of poly(D,L-lactic-co-glycolic acid) (PLGA)/poly(ethyleneglycol) (PEG)
      di-block copolymers were synthesized by ring-opening polymerization of D,L
      lactide and glycolide with different molecular weights of monomethoxy
      polyethyleneglycol (mPEG) 750, 2000 and 5000 as an initiator. The bulk properties
      of these co-polymers were characterized by using 1H NMR spectroscopy, gel
      permeation chromatography, differential scanning calorimetry (DSC). Electron
      spectroscopy for chemical analysis (ESCA) results, in which the blend films with
      the di-block copolymers showed increasing surface oxygen atomic percentage with
      increasing PEG chain length, indicate that PEG chain segment in the di-block
      copolymers is surface oriented and enriched onto the surface of the blend films.
      The extent of protein adsorption onto the surface of these blend films was
      studied, using iodine radio-labeled human serum albumin, gamma globulin and human
      growth hormone. The protein adsorption amount was reduced for the blend films
      prepared with PLGA/PEG 750 and 2000 di-block copolymers, but increased to a great
      extent for PLGA/PEG 5000 di-block copolymer. This is due to the increased water
      uptake capacity of the blend film, which absorbed more protein molecules into a
      swollen polymer matrix in addition to surface adsorption.

PMID- 10915959
TI  - Antifungal activity of silver and zinc complexes of sulfadrug derivatives
      incorporating arylsulfonylureido moieties.
AB  - Two well known antimicrobial sulfonamides, sulfadiazine and sulfamerazine were
      reacted with arylsulfonyl isocyanates, affording several new arylsulfonylureido
      derivatives. These compounds were subsequently used as ligands (in the form of
      conjugate bases, as sulfonamide anions) for the preparation of metal complexes
      containing silver and zinc. The newly synthesized complexes, unlike the free
      ligands, proved to act as effective antifungal agents against several Aspergillus
      and Candida spp., some of them showing activities comparable to ketoconazole,
      with minimum inhibitory concentrations in the range of 1.5-5 microg/ml. The
      mechanism of antifungal action of these complexes seems to be different from that
      of the azole antifungals acting as lanosterol-14-alpha-demethylase inhibitors.
      Levels of sterols assayed in the fungi cultures treated with these new
      antifungals were equal in the absence or in the presence of the tested compounds.
      This is in strong contrast with similar experiments in which ketoconazole has
      been used as antifungal, when drastically reduced ergosterol amounts could be
      detected. Thus, it is probable that the inhibition of phosphomannose isomerase, a
      key enzyme in the biosynthesis of yeast cell walls, imparts antifungal activity
      to the new metal complexes reported here.

PMID- 10915960
TI  - Synthesis of new potent and selective aromatase inhibitors based on long-chained
      diarylalkylimidazole and diarylalkyltriazole molecule skeletons.
AB  - A series of long-chained diarylalkylimidazoles and diarylalkyltriazoles were
      synthesized and evaluated for the inhibitory potency for aromatase (estrogen
      synthetase) activity in human placental microsomes. The relative specificity of
      inhibition was evaluated by measuring the inhibition of cholesterol side-chain
      cleavage enzyme (desmolase) in human placental mitochondria and the inhibition of
      7-ethoxycoumarin O-deethylase (a typical drug-metabolizing enzyme activity) in
      rat liver microsomes. The structural requirements including substituent effects
      for the strongest potency and for the highest specificity were delineated.
      alpha,omega-Diarylalkyltriazoles and imidazoles were the most interesting
      molecules, in which the geometric and optical isomerism displayed remarkable
      selectivity for aromatase inhibition.

PMID- 10915961
TI  - The properties of amylose-ethylcellulose films cast from organic-based solvents
      as potential coatings for colonic drug delivery.
AB  - The purpose of the study was to establish the physico-mechanical and
      digestibility properties of water-miscible organic solvent-based amylose
      ethylcellulose films as potential coatings for colonic drug delivery. Free films
      containing different ratios of amylose to ethylcellulose were cast from the water
      miscible organic solvent, ethyl lactate, in combination with the plasticiser,
      dibutyl sebacate. The resultant mixed films were characterised in terms of
      tensile strength and elasticity, polymer miscibility, permeability, and
      digestibility under simulated colonic conditions. Films containing higher
      concentrations of amylose displayed increasing weakness and softness and faster
      permeation to hydrogen ions compared to films with lower amylose content. No
      apparent miscibility was detected between the amylose and ethylcellulose,
      regardless of film composition. The films were found to be susceptible to
      digestion by bacterial enzymes within a simulated colonic environment. The extent
      of digestion was directly proportional to the amount of amylose present within
      the film. Overall, the results suggest that such amylose-ethylcellulose films
      could be used as coatings for drug delivery to the colon.

PMID- 10915962
TI  - The synthesis of metoprolol monitored using Raman spectroscopy and chemometrics.
AB  - The synthesis of Metoprolol base was studied using Raman spectroscopy with a 785
      nm laser, optical fibres, a holographic transmission grating, confocal optics and
      a charge-coupled device (CCD) detector. The reaction mixture was heated according
      to a temperature gradient and spectra of the reaction mixture were obtained by
      focusing the laser beam through ordinary reaction flasks. Because of overlapping
      bands, multivariate techniques such as principal components analysis (PCA) and
      partial least-squares projections to latent structures (PLS) were used in the
      evaluation of the obtained spectra. The use of PCA or PLS against time does not
      require any calibration samples and a quantitative calibration is not necessary
      in order to monitor the reaction. A method for reaction endpoint determination,
      based on euclidean distances in the score space, is presented. The use of
      multivariate batch control charts have been demonstrated and a number of problems
      and solutions regarding the sample presentation have been discussed. The effect
      of spectral pretreatment on the multivariate results is shown and discussed. The
      monitoring results show that the time to produce Metoprolol base could be
      reduced.

PMID- 10915963
TI  - Piperazinylalkyl prodrugs of naproxen improve in vitro skin permeation.
AB  - Novel morpholinyl (4a) and piperazinylalkyl (4b-e) esters were synthesized and
      evaluated in vitro for their properties as bioreversible topically administered
      dermal prodrugs of naproxen. These ionizable prodrugs exhibited various aqueous
      solubilities and lipophilicities, depending on the pH of medium. As indicated by
      octanol-buffer partition coefficients (logP(app)) at pH 7.4, all of the prodrugs
      were significantly more lipophilic (logP(app)=0.7-3.9) than naproxen
      (logP(app)=0.3). Furthermore, the most aqueous of the soluble prodrugs (4b-d)
      were only 2-3-fold less soluble in an aqueous buffer of pH 7.4 ( approximately 30
      50 mM) than was naproxen ( approximately 100 mM). At a pH of 5.0, prodrugs showed
      a generally higher aqueous solubility and similar logP(app) values, compared to
      naproxen. The chemical and enzymatic hydrolysis of prodrugs at 37 degrees C was
      investigated in aqueous buffer solutions (pH 5.0 and 7.4) and in 80% human serum
      (pH 7.4), respectively. The prodrugs showed moderate chemical stability
      (t(1/2)=15-150 days at pH 5.0), and they were hydrolyzed enzymatically to
      naproxen, with half-lives ranging from 0.4 to 77 min. In permeation studies using
      post-mortem human skin in vitro, the flux of naproxen was 6.5 and 1.6 nmol/cm(2).
      h in a saturated aqueous buffer vehicle of pH 7.4 and 5.0, respectively. Among
      the prodrugs, two piperazinyl derivatives (4c and 4d) resulted in a 9- and 4-fold
      enhancement of permeation, respectively, when compared to naproxen itself at pH
      7.4. 4c also resulted in a significantly (4-fold) better permeation than naproxen
      at pH 5.0. In conclusion, piperazinyl esters improved skin permeation of naproxen
      and are promising prodrugs of naproxen for topical drug delivery.

PMID- 10915964
TI  - Kinetics of propranolol uptake in muscle, skin, and fat of the isolated perfused
      rat hindlimb.
AB  - The tissue distribution kinetics of a highly bound solute, propranolol, was
      investigated in a heterogeneous organ, the isolated perfused limb, using the
      impulse-response technique and destructive sampling. The propranolol
      concentration in muscle, skin, and fat as well as in outflow perfusate was
      measured up to 30 min after injection. The resulting data were analysed assuming
      (1) vascular, muscle, skin and fat compartments as well mixed (compartmental
      model) and (2) using a distributed-in-space model which accounts for the
      noninstantaneous intravascular mixing and tissue distribution processes but
      consists only of a vascular and extravascular phase (two-phase model). The
      compartmental model adequately described propranolol concentration-time data in
      the three tissue compartments and the outflow concentration-time curve (except of
      the early mixing phase). In contrast, the two-phase model better described the
      outflow concentration-time curve but is limited in accounting only for the
      distribution kinetics in the dominant tissue, the muscle. The two-phase model
      well described the time course of propranolol concentration in muscle tissue,
      with parameter estimates similar to those obtained with the compartmental model.
      The results suggest, first that the uptake kinetics of propranolol into skin and
      fat cannot be analysed on the basis of outflow data alone and, second that the
      assumption of well-mixed compartments is a valid approximation from a practical
      point of view (as, e.g., in physiological based pharmacokinetic modelling). The
      steady-state distribution volumes of skin and fat were only 16 and 4%,
      respectively, of that of muscle tissue (16.7 ml), with higher partition
      coefficient in fat (6.36) than in skin (2.64) and muscle (2.79).

PMID- 10915965
TI  - Bisphosphonate prodrugs: synthesis and in vitro evaluation of alkyl and
      acyloxymethyl esters of etidronic acid as bioreversible prodrugs of etidronate.
AB  - The synthesis and preliminary evaluation of novel alkyl and acyloxymethyl esters
      of etidronic acid as etidronate prodrugs is reported. Tetramethyl ester of
      etidronic acid was found be isomerized at pH 7.4 and P-C-P bridge was rearranged
      to P-C-O-P. This unwanted process was prevented via acylation of the bridging
      carbon's alcohol group. Acylation showed to be stable if one or more phosphonic
      OH- groups were substituted. However, when none of the phosphonic OH- groups were
      substituted, the acylation was chemically hydrolysed and the parent drug was
      released. This finding was successfully applied in the design of
      tetrapivaloyloxymethyl ester of acetylated etidronic acid which released
      etidronic acid via enzymatic (first step) and chemical (second step) hydrolysis
      in liver homogenate. However, the corresponding tri-substituted pivaloyloxymethyl
      ester having adequate water-solubility and lipophilicity (logP(app) 0.6 at pH
      7.4), is probably the most potential prodrug candidate reported to enhance the
      oral bioavailability of etidronate.

PMID- 10915967
TI  - [EVolution of research strategies and development in the field of drugs].
AB  - In the field of drug discovery, strategies have moved on quickly over the last
      few years. Development of new disciplines as well as technical advancements in
      many fields, such as pharmacodynamics, pharmacokinetics, drug metabolism,
      pharmaceutics and toxicology have enabled earlier and improved selection of
      development candidates. These new avenues of research, using many often the
      progress in genomics and proteomics, have already led to the elucidation of
      mechanisms of action unknown to date, ending potentially in new medicines.

PMID- 10915968
TI  - [Some thoughts on therapeutic research].
AB  - Today, and no doubt for a long time to come, nature will be the main source of
      novel active drugs. The study of the mechanisms of action of these drugs will
      produce unexpected progress in biology, confirming the premonitory opinion stated
      by Claude Bernard more than a century ago that "Drugs are the reagents of
      biology". In France, research performed in the pharmaceutical industry can take
      legitimate pride in a number of remarkable discoveries. It is regrettable however
      that collaboration between scientists from private companies and those working in
      academic institutions is not adequately developed. Adaptation of biomedical
      curricula for various professions concerned with health in general (physicians,
      pharmacists, dentists, veterinarians, physiotherapists, etc.) including, among
      other steps, a reduction in the number of Schools of Pharmacy and/or the creation
      of Advanced Schools of Drug Research and Development should provide a new impetus
      to therapeutic research, thereby stimulating its creativity and efficacy.

PMID- 10915969
TI  - [Training research scientists for drug discovery].
AB  - National policy for pharmaceutics depends on the quality of the women and men who
      put it into practice. Long term investment in teaching of both research and drug
      development is therefore necessary. In the past our medical, pharmacology and
      veterinary schools have trained the directors and managers of the pharmaceutical
      industry. This is no longer the case today, and not only in research and
      development. Pharmacology schools in particular have not, on the whole, been able
      to incorporate the conceptual and technological requirements of contemporary
      pharmaceutic innovation. Profound changes in teaching 1st and 2nd cycle
      university courses will be necessary in order for pharmacology and medical
      schools to train students who will be not only competent in their specialty but
      also expert in drug discovery, able to play a role in the French pharmaceutical
      industry (and worldwide) and to become research scientists and professors who are
      respected by the international scientific community.

PMID- 10915970
TI  - [Discussion--round table--conclusions].

PMID- 10915971
TI  - [Chirality and drugs].
AB  - The two enantiomers of a chiral drug may have vastly different pharmacodynamic
      and pharmacokinetic properties. As a result, the research and development of
      chiral drugs raises specific problems some of which are discussed here. Thus,
      various pharmacokinetic interactions may involve two enantiomers, as seen for
      example when one enantiomer inhibits the metabolism of the other and modifies its
      effects. A different situation occurs when a third compound stereoselectively
      inhibits the metabolism of one of the two enantiomers. Another problem examined
      here results from the lack of configurational stability of some chiral drugs, a
      little known phenomenon whose consequences can be of pharmacological or
      pharmaceutical significance depending on the rate of the reaction of racemization
      or epimerisation. In-depth investigations are needed before choosing between a
      eutomer or a racemate.

PMID- 10915972
TI  - [Interactions and incompatibilities in prescription drugs. Incidents in dental
      surgery].
AB  - Drug interactions can be classified according to their pharmacodynamic and
      pharmacokinetic mechanisms. Pharmacodynamic interactions are observed when two
      drugs share a common effect or have the same effect on different receptors of a
      common function. They can be predicted if the elementary effects of each drug are
      known. Such are pharmacodynamic interactions are particularly interesting as they
      are selective for the common effect(s). Pharmacokinetic interactions are more
      difficult to predict. They occur when one drug modifies the pharmacokinetic
      parameters of a second drug. Modification may involve variations in oral
      absorption, tissue distribution, rate of metabolism and/or rate of renal
      excretion. This interaction cannot be selective as drug concentrations are
      modified, affecting all the concentration-dependent effects. Mastering drug
      interactions involve the knowledge of the underlying mechanisms. Answers to
      following questions are needed: does the association produce conjugated effects?
      can one drug modify pharmacokinetic parameters of another? Potentially toxic
      effects may be suspected when at least one drug involved is known for its
      toxicity. Risk is increased when it also exhibits a narrow range between active
      and toxic concentrations. Many databases in printed form or as interactive
      software provide information on drug interactions. Clinicians can also consult a
      Pharmacovigilance Center for a safe prescription procedure. Finally, the main
      danger lies in the simultaneous prescriptions by different practitioners unaware
      of their colleagues prescription. In this case, the pharmacist plays an important
      role of evaluation of the drugs prescribed.

PMID- 10915974
TI  - [Differentiation of hepatic and hematopoietic stem cells: study of liver
      regulation protein (LRP)].
AB  - In the adult liver, the plasma membrane Liver Regulating Protein (LRP) has been
      found to participate in the recognition signals between hepatocytes and rat liver
      epithelial cells (RLECs) and to play a critical role in the functional stability
      of hepatocytes. Here, we report the involvement of LRP in hematopoiesis. First,
      LRP was evidenced in the hematopoietic fetal rat liver and in adult rat bone
      marrow. Then, the involvement of LRP in adult rat and human hematopoiesis was
      investigated in coculture of hematopoietic cells with RLECs. In the rat, RLECs
      sustain long-term production of hematopoietic cells and committed progenitors as
      well as bone marrow stroma cells. These effects can be specifically blocked by
      addition of anti-LRP antibodies to both culture systems. The supportive activity
      of RLECs on human hematopoiesis was assessed by comparison to the reference MS-5
      cell line from both unifractioned and purified CD34(+)CD38(-) hematopoietic
      cells. Taken together, our results argue for the involvement of LRP in
      heterotypic interaction signals mediated by RLEC and bone marrow stromal cells
      which lead to hematopoietic primitive progenitors development. They might lead to
      interesting applications in fundamental research, pharmacology and therapeutics.

PMID- 10915973
TI  - [Synthesis and antidepressive activity study of aryl and heteroaryl carboxamides
      of benzylpiperazine].
AB  - The synthesis of 44 original amide derivatives of benzylpiperazine and some
      analogues of befuraline and piberaline is reported. All compounds have been
      tested as antidepressive agents. According to the tests, amides 1, 24 and mainly
      31 (dihydrobefuraline) seem to provide elevated antidepressive activity.

PMID- 10915975
TI  - [Inefficacy of N-methyl-D-aspartate receptor complex antagonists on behavioral
      and histologic consequences of global cerebral ischemia in rats].
AB  - Glutamic acid, an excitatory amino acid, has been proposed to play a major
      deleterious influence in cerebral ischemia. However, the neuroprotective activity
      of various glutamate receptor antagonists is often low or absent, according to
      the animal model used. In the present study, we examined the effect of several
      antagonists acting on glutamate receptors of the N-methyl-D-aspartate (NMDA) type
      in rats submitted to a brief (5 minutes) global cerebral ischemia. The different
      compounds used were poorly active or inactive on behavioural and histologic
      alterations induced by ischemia. Our results suggest that, in this model,
      overactivation of NMDA receptor complex does not play a predominant role in the
      pathogenesis of ischemic brain damage.

PMID- 10915977
TI  - [Europe and medicines: role of the EMEA].
AB  - F. Sauer. Ann Pharm Fr 2000, 58: 278-285. The new European authorization system
      has made considerable progress since 1995. The European Agency for the Evaluation
      of Medicinal Products (EMEA) is primarily responsible for the scientific
      evaluation of applications for a European marketing authorization for medicinal
      products derived from biotechnology and other high technology (centralised
      procedure). For other products, the EMEA arbitrates where mutual recognition of
      national marketing authorizations between the Member States is not possible
      (decentralised procedure). The EMEA co-ordinates the scientific resources made
      available by the national competent authorities of the Member States, including a
      network of over 2 000 European experts. The Opinions of the scientific committees
      of the EMEA (Committee for Proprietary Medicinal Products, CPMP, and Committee
      for Veterinary Medicinal Products, CVMP) are enforced by the European Commission,
      which has so far authorized 69 medicinal products for human and veterinary use.
      The confidence of industry, health professionals and consumers in the system is
      clear. European patients are now able to have speedier access to new drugs,
      usually within one year. The new system also helps to reinforce the safety of
      medicines for humans and animals, particularly through a pharmacovigilance
      network and the establishment of safe limits for residues in food-producing
      animals.

PMID- 10915976
TI  - [Therapeutic effect of Olea europea var. oleaster leaves on carbohydrate and
      lipid metabolism in obese and prediabetic sand rats (Psammomys obesus)].
AB  - Sand rats develop obesity, insulin-resistance, hyperlipidemia and prediabetes,
      when given a standard laboratory chow diet. We have used this model to
      demonstrate the beneficial action of olea europea var. oleaster leaves to
      regulate unbalanced metabolism. 32 sand rats fed on hypercaloric diet during 7
      months, were divided into 3 groups: controls (n=10), treated by plant (n=13) and
      treated by simvastatin (Zoco); hypocholesterolemic drug. The plant decoction
      prepared at 10% was given orally at the rate of 1.5 ml/100g during 3 months.
      Results show that the plant presents a hypocholesterolemic effect (42%) related
      to decreases in LDL and VLDL cholesterol. In addition, hypoglycemic (16%) and
      antihyperglycemic (40%) effects were observed accompanied by a 27% decrease in
      insulin. Chronic treatment with Zocor reduced total cholesterol (32%), LDL and
      VLDL cholesterol. Both of treatments produced no significantly reduction in
      plasma levels of triglycerides and HDL cholesterol. No noxions effect of this
      plant have been observed in usual doses.

PMID- 10915978
TI  - [The WEB and surgery: fad or revolution?].

PMID- 10915979
TI  - [Abbreviated laparotomy].
AB  - The decision to perform damage control laparotomy in a critically injured
      patients depends on the risk of life-threatening coagulopathy. The main decision
      criteria are: presence of concomitant injuries, patient history, shock,
      transfusion volume, hypothermia and acidosis. The aim of surgery is to achieve
      satisfactory hemostasis, limit peritoneal thermal loss, and perform physiological
      restoration as rapidly as possible in the intensive care unit. This includes
      gauze packing of major liver or retroperitoneal injuries and ligation of injured
      blood vessels. Injuries to the intestine and the urinary tract are sutures,
      stapled or drained. If the skin borders cannot be reapproximated because of
      excessive abdominal tension, a wall prosthesis should be used to avoid abdominal
      compartment syndrome. Reoperation is a dangerous procedure in the immediate
      postoperative period but must be proposed later for reexploration or damage
      repair.

PMID- 10915980
TI  - [Management of duodenal-pancreatic endocrine tumors].
AB  - Endocrine tumors of pancreas and duodenum have a common diagnostic and
      therapeutic approach. Surgery has a key role to play in the management of
      patients with such tumors. According to a particular patient, this role is to get
      under control a secretory syndrome which is refractory to medical therapy, to
      eradicate a malignant or a premalignant tumor, to produce cytoreduction by
      debulking, or to palliate complications due to massive regional extension of a
      malignant tumor.

PMID- 10915981
TI  - [Progress in the treatment of inguinal hernia].
AB  - The aim of surgical treatment of inguinal hernia is to a) reduce post-operative
      pain and discomfort to a minimum allowing patients to return to the activities as
      rapidly as possible, and b) hold the recurrence rate under 1%. The Shouldice
      technique remains the gold standard; its real recurrence rate is about 5%.
      Applying a mesh in the retroperitoneal space by laparoscopy is a good approach
      and can theoretically reach both aims. In current practice however, laparoscopy
      is not always favorable: general anesthesia is mandatory, technical pitfalls lead
      to morbidity and later to recurrences. Tension-free procedures would provide the
      best compromise for achieving the two advantages of: a) reducing pain, discomfort
      and recurrence risks by eliminating tension and, b) local and or loco-regional
      anesthesia.

PMID- 10915983
TI  - [Surgical treatment of rectoceles by the perineal-vaginal route: rectal folds,
      vaginal sacrospinal fixation and posterior perineorrhapy].

PMID- 10915982
TI  - [Extended colpohysterectomy with pelvic node dissection].

PMID- 10915984
TI  - [Bladder ureter reimplantation after section of the pelvic ureter].

PMID- 10915985
TI  - [ Thoracoepigastric anastomosis can constitute a major danger during transverse
      laparotomies in cases of Leriche syndrome].

PMID- 10915987
TI  - [ [In Process Citation]

PMID- 10915986
TI  - [55-year-old woman with icterus].

PMID- 10915988
TI  - [The role of the radiologist].

PMID- 10915989
TI  - [Sturge-Weber syndrome. The current neuroradiologic data].
AB  - Sturge-Weber syndrome (SWS) is a rare congenital sporadic disease with neuro
      ocular and cutaneous vascular findings. Clinically, the full-blown condition
      consists of a facial port-wine stain (PWS) involving the V1 facial trigeminal
      skin area, alone or in combination with V2 and V3PWS, seizures and ocular
      abnormalities (glaucoma and choroidal angioma). Radiologically, a leptomeningeal
      (pial) capillary and venous malformation, mostly located in the parieto-occipital
      area, cerebral atrophy and calcifications are demonstrated. An ipsilateral
      enlarged choroid plexus may be an early anatomic symptom. Developmental venous
      anomalies (DVA) of the brain are sometimes associated. MR with gadolinium
      enhancement is the optimal neuro-diagnostic imaging technique for the screening
      of infants with an at-risk V1PWS, as well as for the follow-up of patients with
      evidence SWS. Accelerated myelination in the involved hemisphere may be an early
      diagnostic feature before 6 months of age. Later, hyperintensity of white matter
      on T2 is considered a symptom of gliosis. Clinically, progression of the diseases
      is associated with anatomic changes and correlates with the extent of the pial
      vascular anomaly, extent and severity of cerebral atrophy, and white matter
      abnormalities. A neonatal neuro-imaging work-up, using CT or MRI, may not
      demonstrate the pial anomaly and should be repeated after 6 to 12 months in an at
      risk infant with V1PWS.

PMID- 10915990
TI  - [Value of MR imaging in the diagnosis of benign uterine conditions].
AB  - Benign diseases of the uterus can be evaluated by ultrasound, magnetic resonance
      imaging (MRI), hysterography, hysterosonography and hysteroscopy. The purpose of
      this review of the literature is to discuss the role of MRI among the different
      imaging modalities for the diagnosis of mullerian abnormalities of the uterus,
      endometrial disease, fibroids and adenomyosis. Particular attention is brought to
      comparative multi-modality studies. The MRI technique, indication and diagnostic
      criteria for various pathological conditions of the uterus are described. The use
      of MRI appears to be cost-effective in the diagnosis of complex mullerian
      abnormalities, endometrial thickening following treatment by tamoxifen, selection
      of candidates for selective myomectomy and the follow-up of medically treated
      adenomyosis.

PMID- 10915991
TI  - [Pituitary gland MRI and Cushing disease: report of 14 operated patients].
AB  - PURPOSE: Evaluate the MR sensibility for detection and localisation of ACTH
      secreting microadenomas of the pituitary gland. PATIENTS: and method. The MRI
      studies of the pituitary gland, performed before transsphenoidal surgical
      exploration, about 14 patients who present clinical and biological signs of
      Cushing disease, were reviewed retrospectively. We have always used unenhanced
      sagittal and coronal spin-echo T1 sequences, and coronal T1 after injection of
      gadolinium (1 Tesla). RESULTS: The global sensibility for detection of an adenoma
      was 100% (84 to 92% when the lesional localisation was considered). The injection
      of gadolinium increased the sensibility of 38 to 42% according the readers. 7 to
      14% of the lesions were isointense after injection. The estimation of lesional
      size after injection was the nearer to the surgical results. The indirect sign
      most frequently seen (35.7 to 64.3%) was focal bulging of the sellar diaphragm.
      The only differences between the different radiologists, statistically
      significant, concerned the lesional size before injection and location of the
      lesion in the sagittal plane. CONCLUSION: This study confirmed the good
      sensibility of contrast-enhanced MRI in detection of ACTH-secreting
      microadenomas. The anatomo-radiological correlations are nevertheless incomplete.

PMID- 10915992
TI  - [Evaluation of radiological medical practice at a hospital during night duty].
AB  - PURPOSE: To evaluate the radiological activity during night duty, in a University
      Hospital. Materials and methods. During 100 days, the radiological activity has
      been evaluated from examinations requiring radiologist (including US and CT,
      special X-ray examinations). The urgent nature and the agreement between the
      suspected disease and the final diagnose have been compared with the level of the
      clinician (medical student, resident, senior). RESULTS: 981 radiological
      examinations were performed on an emergency basis. In 39%, the examination was
      urgent or very urgent and for 61%, little urgent or non-urgent. The level of the
      clinician was correlated with the degree of emergency evaluated by the
      radiologist and with the agreement between suspected disease and the final
      diagnose (p<0. 0001). CONCLUSION: During night duty, the medical activity in
      radiology is not justified only by emergency, but also by the continuous hospital
      activities. Better formation of the physician is required to limit the number of
      examinations.

PMID- 10915993
TI  - [MR cholangiography in biliary complications after liver transplantation in
      children].
AB  - PURPOSE: To evaluate the role of MR Cholangiography in a pediatric population
      with biliary complications after liver transplantation and particularly with
      anastomotic stenosis. PATIENTS AND METHODS: Ten MR cholangiography studies were
      performed in 10 children with liver transplant who were suspected of having
      biliary complications between December 1996 and April 1998. The findings on MR
      were correlated with the results from liver biopsy, liver ultrasound, liver
      function tests and with clinical information when available. RESULTS: MR
      cholangiography identified 9 children with biliary tree dilatation, 4 with
      anastomotic stenosis, 5 with multiple bile ducts stenosis, 2 with stones in the
      intra-hepatic biliary tree and 2 with abnormalities suspicious for acute
      cholangitis. Three of 4 anastomotic stenoses were confirmed and treated by
      percutaneous cholangiography. There was no correlation between the different
      exams in 6 children but MR cholangiography confirmed the final diagnosis.
      CONCLUSION: In children with liver transplantation, MR cholangiography may be
      useful to evaluate and to confirm a diagnosis of bile duct complications and it
      is helpful in the absence of correlation between liver biopsy, ultrasound and
      liver function test.

PMID- 10915994
TI  - [The cost of breast cancer screening in France].
AB  - PURPOSE: This paper presents the cost of two decentralised breast cancer
      screening programmes in France, in the Bas-Rhin and the Bouches du Rhone
      districts. Materials and methods. The costs directly related to running the two
      screening programmes were collected for the time period 1990-1997. Only direct
      costs of each programme, excluding assessment and treatment costs, are included
      in the cost analysis. Costs are presented per screening period, per programme
      attender and per cancer detected by screening. RESULTS: The screening programme
      costs an average of 397 francs per woman screened and 90,828 francs per cancer
      detected in the Bas-Rhin, and 379 francs and 76,159 francs, respectively, in the
      Bouches du Rhone. CONCLUSIONS: These costs are high compared to those of existing
      centralised programmes. Further research is needed to investigate means of
      ensuring the optimal efficiency of these programmes. The results of this study
      may help guide future decisions on the further development of breast cancer
      screening in France.

PMID- 10915995
TI  - [Metastasis in pulmonary arteries].
AB  - We report two cases of pulmonary tumor emboli. The first patient had a
      chondroblastic osteosarcoma of the pelvis while the second patient had a
      seminoma. The possibility of tumor emboli should be entertained in patients with
      prior history of malignancy presenting with enlargement of the pulmonary arteries
      and thrombus enhancement on delayed scans.

PMID- 10915996
TI  - [Chronic hematic cyst of the orbit (orbital subperiosteal hematoma)].
AB  - A case of chronic hematic cyst of the orbit which caused unilateral globe
      displacement with painful diplopia is described in a 72-year-old man. CT scans
      showed an extraconal soft tissue mass located between the orbital roof and the
      superior rectus muscle with a bone lysis. Characteristic appearance on MRI
      (benign signs, subperiosteal localization of the hematoma) has been confirmed by
      removal surgery. Chronic hematic cyst of the orbit is uncommon and MRI is helpful
      to establish this diagnostic.

PMID- 10915997
TI  - [Hajdu-Cheney syndrome: an unusual cause of acro-osteolysis].
AB  - We report a case of Hajdu-Cheney syndrome. This cranioskeletal dysplasia is
      characterized by band-like acro-osteolysis of the tufts middle thirds.
      Differential diagnosis of band-like acro-osteolysis are discussed.

PMID- 10915998
TI  - [Neurotrichinosis: a case report with MRI evaluation].
AB  - Neurological complications are rare in trichinosis. A case of trichinosis
      involving the central nervous system documented by MRI is presented. To our
      knowledge, only three cases of neurotrichinosis with MRI abnormalities have been
      already reported. The physiopathological mechanism are discussed (transport of
      the parasite through the blood-stream, immuno-allergic reaction or eosinophilic
      neurotoxic effect).

PMID- 10916000
TI  - [The radiologist: a superfluous technologist?].

PMID- 10915999
TI  - [What is your diagnosis? Bilateral infundibulopelvic hypoplasia].

PMID- 10916001
TI  - [Multi-row detectors: a significant advance towards volumetric CT].

PMID- 10916002
TI  - [A decentralized breast cancer screening program in the French department of Bas
      Rhin].
AB  - Since 1989, in the French department of Bas-Rhin, a breast cancer screening
      program in going on and its results are presented here. This program, concerning
      women of 50 to 65 years-old, is decentralized, based on private or public
      radiologists and the motivation of women because there is no invitation. The
      interval between screening test is 2 years. After 8 years, the results are rather
      satisfactory: participation rate of the initial cohort is 77% in December 31st
      1997, participation at incident screenings is above than 85%, early indicators
      (recall rate, detection rate, PPV of screening, PPV of biopsy) are improving with
      time to attain numbers like international studies. The ADEMAS program shows that
      a decentralized screening program, based on existing medical structures is
      possible in France. Anyway, it must be organized, evaluated at any time, with a
      quality assurance system to guarantee the women the best taking charge.

PMID- 10916003
TI  - [Diffusion- and perfusion-weighted MR imaging during the hyperacute phase of
      stroke].
AB  - The sensitivity of diffusion-weighted MR imaging to detect a lesion within 6
      hours of stroke onset was approximately 90%. The false negative results were
      usually small lesions (1 ml), were seen early, and were usually located in the
      brain stem. The specificity of this technique was nearly 100% when it was used
      correctly. The volume and the value of the apparent diffusion coefficient of the
      detected lesions provided prognostic information. After injection of a contrast
      agent (perfusion imaging), a time series of volumes were obtained using a T2*
      sensitive gradient echo EPI sequence. Hemodynamic perturbations of the cerebral
      parenchyma could be detected as well as the type of perturbation in the lesion. A
      map representing the mean transit time for each voxel was used to define the
      maximum volume of the perturbation. A hemodynamic penumbra was defined to be when
      this volume was larger than the volume detected on the diffusion images. The
      quantitative measure of cerebral blood flow could predict the irreversibility of
      the lesions when the value was below 18 ml/min/100g, and the extension of the
      ischemia in the penumbra zone when the value was below a threshold of 30
      ml/min/100g.

PMID- 10916004
TI  - [MRI of the brain in the evaluation of children with developmental delay].
AB  - PURPOSE: To analyze the diagnostic value of MRI in children with developmental
      delay. Materials and Methods. From 1991 to 1997, 224 examinations were performed.
      Retrospective analysis of clinical findings and diagnostic yield was carried out.
      RESULTS: MRI was abnormal in 109 cases. It never resulted in any patient care
      modification. 55 malformations, 12 cases of cerebral atrophy, 7 cases of white
      matter disease and 2 patients with phakomatose were identified. Myelination delay
      (26 cases), increased signal of posterior white matter on T2-weighted images (9
      cases) or widened Virchow-Robin spaces (3 cases) were frequently encountered, but
      it remained unclear whether they represented normal variants or true
      abnormalities. Post ischemic lesions were identified in 10 cases. Frequency of
      abnormal studies was significantly lower in children with developmental delay and
      behavioral disorders than in patients with other clinical presentation.
      CONCLUSION: Diagnostic yield of cerebral MRI can justify its performance by
      comparison to other imaging modalities. It should be correlated with other
      investigations performed in a specialized unit. Its main interest is for
      classification and research. Risk of sedation or anesthesia should also be taken
      in account. Risk can be lowered using adequately equipped MR units and organizing
      procedures in collaboration with anesthesiologists.

PMID- 10916005
TI  - [Imaging features of gastric stromal tumors: radiologic-pathologic correlation.
      Report of 4 cases].
AB  - GOAL: This study concerns the new anatomo-pathologic semantics of the ancient
      gastric leiomyoblastoma that become gastric stromal tumors (GST) and identified
      as stemming of "pace-maker" cells of Cajal related to the immunohistochemical
      characterization of the phenotype. MATERIAL: and methods. We limited the study to
      the mesenchymatous tumors to "pacemaker" cells. For this purpose, we report four
      documented observations of gastric stromal tumors correlated to the histology and
      to the immunohistochemical study. RESULTS: Although some signs are often
      described (exogastric development, heterogeneity with cystic and necrotic
      component, predominating peripheral enhancement...), radiological aspects of
      these tumors are not specific because, analogues to the other mesenchymal tumors
      (leiomyoma or schwannoma). The topographic diagnosis is difficult, realized by
      echoendoscopy, CT scan and MRI. The irregularity of contours evokes the
      malignancy as hemoperitoneum. GST do not show lymphophilic behavior that
      differentiates them from the adenocarcinomas and gastric lymphomas. The surgical
      treatment is the best treatment, allowing the immuno-histological diagnosis of
      certainty from the complete operative specimen. CONCLUSION: Some tumors are
      difficult in classifying despite classic histology necessitating
      immunohistochemical tests for the identification of muscular, nervous, autonomous
      nervous system flexion of mesenchymatous tumors with epithelioid or spindle cells
      of the gastrointestinal tract. Then a radio-clinical follow-up is therefore
      indicated: the evolution is the alone real marker of malignancy.

PMID- 10916006
TI  - [Pulmonary embolism: is scintigraphy useful after initial angio-CT?].
AB  - PURPOSE: To assess the value of ventilation-perfusion scintigraphy after an
      initial helical CT with absence of pulmonary embolism (PE). MATERIAL: and
      methods. Twenty eight consecutive patients with clinical suspicion of pulmonary
      embolism underwent helical CT scan to look for an intra-luminal clot. When the CT
      scan was positive for PE, diagnosis was retained. If the result was negative, a
      ventilation-perfusion scintigraphy was performed. If the result was also
      negative, diagnosis of PE was excluded. In case of discrepancy, a pulmonary
      angiography was performed and used as gold-standard. RESULTS: Twenty-one patients
      showed PE at CT-angio and 7 did not. Two of these 7 had normal or low probability
      scintigraphy, excluding diagnosis of PE. One had intermediate V/P scan and 4 had
      high probability V/P scan. For these 5 discrepancies, none of them had PE on
      angiography. CONCLUSION: In this population, scintigraphy was not appropriate
      after a negative CT-angio for PE. In case of persistent doubt after a normal
      initial helical CT, pulmonary angiography is required

PMID- 10916007
TI  - [Air trapping revealing endobronchial tuberculosis].
AB  - We report a case of endobronchial tuberculosis located in the main left bronchus
      suspected on a CT scan and assessed by fiberoptic bronchoscopy. This localisation
      is not unusual, and is often associated with a normal chest radiography. Air
      trapping present on high resolution CT scan led to focus the examination on
      proximal airways and to suspect their involvement. This observation underlines
      the value of expiratory CT scan in demonstrating proximal stenosis of main
      bronchi.

PMID- 10916008
TI  - [Accessory retrograde aneurysmal aortic lumen supplying the inferior mesenteric
      artery].
AB  - We report the case of a patient with infrarenal abdominal aortic aneurysm with
      mural thrombus covering the ostium of a patent inferior mesenteric artery (IMA).
      The IMA was supplied via flow from an accessory aneurysmal lumen within the mural
      thrombus that filled retrogradely from the aorta. This unusual pattern,
      associated with calcifications within the thrombus, raised the possibility of
      chronic aortic dissection.

PMID- 10916009
TI  - [Infectious aneurysms of the cavernous carotid artery].
AB  - We describe 3 patients who developed infectious aneurysms of the cavernous
      carotid artery. The aneurysms were due to sphenoidal sinusitis in two patients
      and due to endocarditis in one. The acute and septic onset of the cavernous sinus
      syndrome, suggested thrombophlebitis of the cavernous sinus in all 3 patients.
      The diagnosis was established by magnetic resonance imaging and magnetic
      resonance angiography. Therapeutic internal carotid artery occlusion was
      indicated for a fissuration of their aneurysm manifested (n=3) by an episode of
      epistaxis (n=2) and blood in sphenoid sinus (depicted by MRI) in one case. We
      discuss the pathophysiology and management of bacterial aneurysms of the
      cavernous carotid artery. Close clinical and imaging follow-up should be
      performed for patients under antibiotherapy. Selective angiography with
      therapeutic occlusion of the carotid artery is discussed in patients with
      persistence of symptoms or if clinical findings are suggestive of fissuration or
      if aneurysmal sac diameter increases on follow-up imaging studies.

PMID- 10916010
TI  - [Infected aneurysm of abdominal aorta: early CT finding].
AB  - Infected abdominal aortic aneurysm is an uncommon but life-threatening disease,
      especially in case of salmonella infection. Early CT findings should be well
      known in order to allow immediate diagnosis and accurate management. The authors
      present an early CT finding of a salmonella infected aneurysm of abdominal aorta
      in an HIV-infected patient. This pattern consists in a slight-enhancing focal
      densification of periaortic soft-tissue, while aorta remains of normal size.
      Within two weeks, infection progressed to the constitution of an infected
      aneurysm. This CT finding seems to be initial to previously described signs.

PMID- 10916011
TI  - [Quid? What is your diagnosis? Diagnosis: Glass foreign body of the posterior
      part of the right thigh].

PMID- 10916013
TI  - [ [In Process Citation]

PMID- 10916012
TI  - [Radiology is dead].

PMID- 10916032
TI  - [Clinical diagnostic criteria in Parkinson's disease and parkinsonian syndromes:
      review of the literature].
AB  - This paper reviews the validity of clinical diagnostic criteria developed for
      Parkinson's disease and parkinsonian syndromes. Proposed criteria are
      predominantly empirical. There are only a few studies with neuropathological
      verifications. For Parkinson's disease and Progressive Supranuclear Palsy
      clinicopathological studies have been performed and led to pathologically based
      criteria. In this context, the specificity and sensitivity of clinical criteria
      could be assessed. Reliability however has seldom been tested. In contrast, the
      proposed criteria for the clinical diagnosis of Multiple System Atrophy and
      Corticobasal atrophy have not been pathologically evaluated.

PMID- 10916033
TI  - [Place of the paraclinical exams in the Parkinson's disease: review].
AB  - The place of the paraclinical exams in the Parkinson's disease is not clearly
      defined currently. We will study successively the various examinations at our
      disposal, the results which one can expect and their possible indications.

PMID- 10916034
TI  - [Diagnostic criteria for idiopathic Parkinson's disease].
AB  - Clinical diagnosis of parkinsonian syndrome is reasonably easy, but the
      distinction between idiopathic Parkinson's disease (IPD) and other parkinsonian
      syndromes (Secondary parkinsonisms and "Parkinsons plus") may be very difficult
      particularly in early cases. A correct diagnosis is not only important for
      counselling and management of patients but also in conducting pharmacological and
      epidemiological studies. A critical analysis of the diagnosis criteria of IPD,
      based on the pathological verification, is discussed from recent data of
      literature. Without any validated and available criteria from functional imaging
      or molecular biology, the most effective diagnostic criteria remain on the
      clinical range; the five most effective criteria are resting tremor, rigidity,
      bradykinesia, asymmetry at onset and marked levoDOPA responsiveness. The
      diagnosis of IPD should be periodically reassessed along the course of its
      natural history.

PMID- 10916035
TI  - [Parkinson's disease and complementary explorations: when and why?].

PMID- 10916036
TI  - [Diagnostic criteria for Parkinson syndromes, expecting Parkinson's disease].

PMID- 10916037
TI  - [Evaluation scales for Parkinson's disease].

PMID- 10916038
TI  - [Rating scales and questionnaires in Parkinson's disease].
AB  - Rating scales and questionnaires used as measurement tools in Parkinson's disease
      are carefully constructed with well-defined items. The validity of a scale is its
      capacity to provide the intended measurement. One can distinguish perceived,
      content, and criteria-based validity as well as construction and sensitivity to
      change validity. The reliability of a scale is the capacity of a scale to produce
      statistically equivalent data in comparable situations. Reliability is composed
      of the following qualities: interobserver reliability, test-retest reliability,
      and internal coherence. UPDRES, mood scales (Hamilton, MADRS, CES-D, BDI), scales
      assessing cognitive disorders (MATTIS, MMSE), and quality of life questionnaires
      designed specifically for Parkinson's disease (PDQL, PDA-39, PDq-8) or for the
      general population (SF-36, SIP, NHP) are used in routine practice, and are
      particularly useful for clinical research. The metrological properties of these
      scales are analyzed here.

PMID- 10916039
TI  - [Rating scales for Parkinson's disease: when and how to use them].
AB  - In Parkinson's disease, rating scales are used to assess the degree of disease
      related disability and to titrate treatment to each phase of the disease course.
      Clinicians should be widely aware of these scales and know how to use them. The
      UPDRS is the most widely used, having proven intra- and inter-observer validity.
      The purely motor items of the UPDRS allow an evaluation of response to
      dopaminergic treatment. Scales including all aspects of the disease, motor,
      cognitive and psychiatric impairment, can also be used. Some of the simple scales
      can be used at consultation or the patientis bedside, others require experience
      in psychological care. They are useful in daily practice for patient follow-up
      and facilitate communication between caregivers. Quality of life scales have been
      developed more recently. These scales take into account the patientis own
      perception of his/her disability and its impact on daily activities. Finally,
      motor and cognitive disability scales are used in clinical research protocols.

PMID- 10916040
TI  - [Contribution and limitations of evaluation scales in Parkinson's disease].
AB  - Rating scales in Parkinson's disease (PD) are generally reliable but are not
      widely used in practice. UPDRS is the core assessment of PD, its metrologic
      properties are well known, and it is simple to use after training. However,
      cognitive and psychic disorders need complementary approaches. For example,
      MATTIS seems to be more appropriate in assessing the cognitive deficit and MADRS
      the depressive symptoms. A patient diary best appreciates motor fluctuations.
      Activities of daily living rated by the UPDRS allow a global assessment of the
      patient handicap that may be completed by "the patient's own point of view"
      through quality of life scales (SF36, PDQ39). For clinical research purposes,
      time tests and dyskinesia scales following the CAPIT or CAPSIT procedure are
      required.

PMID- 10916041
TI  - [Therapeutic strategies recommended for early stage Parkinson's disease].

PMID- 10916042
TI  - [Dopa-therapy in the treatment of early stage Parkinson's disease].

PMID- 10916043
TI  - [Role of dopaminergic agonists].
AB  - The usefulness of an initial treatment of Parkinson's disease with a dopamine
      agonist has now been studied for more than 20 years. The first clinical trials
      compared the long-term out come of patients receiving early bromocriptine or
      lisuride to those receiving initial L-dopa. These pilot data suggested that the
      early use of these agonists (combined early or supplemented later with low doses
      of L-dopa) reduced the risk of occurence of motor complications such as
      dyskinesia and/or fluctuations. These initial conclusions were however criticised
      because of methodological limitations in study design. The recent results from
      new large prospective randomized double-blind 5-year L-dopa-controlled trials
      using newer dopamine agonists (cabergoline and ropinirole) confirmed the findings
      of the previous pilot studies. Therefore, one now generally agrees that the early
      use of such agonists (to which low doses of L-dopa may be added as a second step
      if necessary to maintain an adequate control of parkinsonian symptoms) is useful
      to reduce the risk of occurence of motor complications. This result is achieved
      without a major increase in the risk of other dopaminergic adverse events
      (digestive, cardiovascular, psychiatric), specially in 'young' patients (before
      70 years).

PMID- 10916045
TI  - [Parkinson's disease: what therapeutic strategy is advisable in early stage
      disease?].

PMID- 10916044
TI  - [What strategies are recommended for early stage disease? Other treatments].

PMID- 10916046
TI  - [ What drug strategies are advisable for patients with advanced-stage
      Parkinson's].

PMID- 10916047
TI  - [Drug treatments and motor complications in advanced stage Parkinson's disease ].

PMID- 10916049
TI  - [Rehabilitation and Parkinson's disease ].

PMID- 10916048
TI  - [Other symptoms of advanced stage Parkinson's disease].
AB  - Autonomic dysfunction, neuropsychiatric problems, axial signs and sleep disorders
      are common complications of advanced Parkinson's disease (PD). Urinary
      disturbance due to detrusor hyperreflexia and iatrogenic orthostatic hypotension
      are prominent dysautonomic signs. Depression and anxiety are frequent but can
      occur exclusively during off periods. A fronto-sub cortical dementia occurs in
      30% of PD patients, but anti-parkinsoniens drugs (APD) can cause hallucinations
      even in non demented PD patients. Axial signs, such as freezing, postural
      instabily or dysarthria become doparesistant. Insomnia, REM sleep disorders. At
      least, pain is very frequent. Exact analysis of these signs is important for an
      adequate treatement: most of them are improved by APD but some of them, like
      orthostatic hypotension or hallucinations, are increased by these drugs.

PMID- 10916050
TI  - [Exercices program and rehabilitation of motor disorders in Parkinson's disease].
AB  - As long as motor disorders are controlled by DOPAtherapy, exercise programs and
      rehabilitation would not appear to be essential for patients suffering from
      Parkinson's disease. Such measures do become necessary however when secondary
      occurrence of motor decline develops. Physical medicine and rehabilitation have
      not been really involved in Parkinson's disease and few articles have assessed
      the value of these programs. In fact, controlled randomized studies have faced
      two kinds of methodological difficulties, those due to rehabilitation practices,
      and those due to Parkinson's disease specificity, especially similarities between
      groups for Hoehn and Yahr stage at study onset and unchanged drug treatment
      during the period of the clinical trial. Assessment has had to rely on scales
      taking into account the main Parkinson impairments (e.g. walking ability,
      postural control, skill), their intensity and also their fluctuation such as on
      off effects. The Unified Parkinson's Disease Rating Scale (UPDRS) looks well
      adapted but has been only recently for such studies. Many exercise programs,
      aiming at improving coordination, sway balance, transfer and gait have been
      proposed in the literature; rhythmic visual or auditory cueing seem quite
      effective. Only four controlled studies with satisfactory methodology are
      available. They could lead to the conclusion that physiotherapy would be
      effective more by reducing daily life disability than by improving Parkinson
      symptoms such as bradykinesia or tremor. To be effectively performed at home,
      these exercises would have to be taught early in the course of the disease and
      during an on phase, physiotherapists giving special attention to postural control
      and prevention of falls. In another controlled randomized study occupational
      therapists successfully trained patients in everyday activities. For the most
      severely impaired patients, rehabilitation and home adaptations are the only
      means to achieve an less dependent status. Multidisciplinary outpatient
      departments providing physical medicine and rehabilitation facilities in addition
      to neurological care would appear to be the best solution for helping Parkinson's
      disease patients cope with their impairments and disabilities.

PMID- 10916051
TI  - [Role of rehabilitation Parkinson's disease, by disease severity and disability
      pattern].
AB  - Physical therapy is recognized as one of the most helpful means of improving the
      disabling side-effects of Parkinson's disease. Techniques which reduce stiffness,
      and improve muscle contracture and respiratory function are well established in
      different fields of rehabilitation including rheumatology and orthopedics.
      Parkinson's disease patients derive an obvious benefit from such treatments,
      suitably adapted to each stage of the disease course. New avenues for
      rehabilitation care include the cognitive approach for learning strategies or
      mental preparation for a given action in an attempt to reduce the akinesia, one
      of the main features of parkinsonism. Attractive as this new approach may be, its
      effectiveness remains to be proven.

PMID- 10916052
TI  - [Rehabilitation of communication disorders and ENT function].

PMID- 10916053
TI  - [Economic aspects of Parkinson disease treatment].

PMID- 10916054
TI  - [Surgical treatments in Parkinson's disease ].

PMID- 10916055
TI  - [Surgical treatment: inclusion criteria].
AB  - Different surgical strategies have been suggested to treat PD patients. Cerebral
      grafting remains experimental and pallidotomy is not performed among the French
      neurosurgery departments. Therefore selection criteria for surgical
      interventional therapies will be only discussed for deep brain stimulation (DBS)
      even if these criteria are not really different between grafting, pallidotomy and
      DBS. Choice of selection criteria is very important in order to separate PD
      patients with a high probability of clinical benefit after surgery from those in
      whom the surgical procedure includes a high risk of morbidity. A selection
      procedure is proposed according to data of the literature and to the results of a
      questionnaire filled by 7 french expert centers involved in surgical therapies of
      PD. The selection procedure in a patient with a parkinsonian syndrome lasting for
      more 5 years has to include:

PMID- 10916056
TI  - [Neurosurgical treatment of Parkinson's disease: which technique is best?].

PMID- 10916057
TI  - [Cost assessment of functional neurosurgery for abnormal movement by stimulation
      of the basal nuclei, particularly the subthalamic nucleus].

PMID- 10916058
TI  - [Recommendations of the jury on diagnosis and treatment of Parkinson disease.
      Short text].

PMID- 10916059
TI  - [Recommendations of the jury on diagnosis and treatment of Parkinson disease.
      Long text].

PMID- 10916060
TI  - Effect of heparin, platelets, activated platelets, platelet fragments, and
      hematocrit on activated clotting time.
AB  - Activated clotting time (ACT) is the most commonly used laboratory test to
      control the heparin effect during extracorporeal techniques. The study was
      undertaken in order to test in vitro the influence of heparin, platelet count,
      hematocrit, platelet fragmentation, and platelet activation on ACT. Blood was
      drawn from volunteer donors into syringes containing citrate. Platelet counts and
      hematocrit were modified. Platelets were fragmented by sonifier or activated by
      collagen and adenosine diphosphate (ADP). Different heparin final concentrations
      were created. Increasing concentrations of heparin had a significant effect on
      ACT. However, it was not predictable in every case in concentrations lower than
      1.0 U/ml. Platelet count generally had no significant effect on ACT. The effect
      of hematocrit was detectable in a group but not in single cases. Fragmented
      platelets significantly shortened ACT only without addition of heparin, and the
      effect was only partly predictable. Activation of platelets by collagen and ADP
      induced no significant changes. Our results show that heparin is reflected by ACT
      but that effect is not predictable in every specific patient. Our results also
      show that other variables that may be altered during extracorporeal techniques
      such as platelet count, hematocrit, activation, and fragmentation of platelets do
      not severely influence the ACT.

PMID- 10916061
TI  - Cytokine induction in patients undergoing regular online hemodiafiltration
      treatment.
AB  - End-stage renal disease (ESRD) patients are known to suffer from chronic
      inflammation as the result of an ongoing subacute cytokine induction, which may
      contribute considerably to dialysis-related, long-term morbidity and mortality.
      Preparation of infusate from cytokine-inducing dialysis fluid and its
      administration in large quantities as well as the use of high-flux membranes bear
      the risk of aggravating the chronic inflammatory response among online
      hemodiafiltration (online HDF) patients. In order to assess the inflammatory risk
      associated with online HDF, we compared the cytokine induction profile of ESRD
      patients receiving either online HDF or low-flux hemodialysis (low-flux HD).
      Specifically, we measured spontaneous and lipopolysaccharide (LPS)-stimulated
      tumor necrosis factor alpha (TNFalpha) and interleukin-1 receptor antagonist (IL
      1Ra) release during ex vivo incubation of whole blood. Ultrapure dialysis fluid
      and polysulfone membranes were used for both treatment modalities. LPS-stimulated
      release of TNFalpha and IL-1Ra was elevated for both online HDF and low-flux HD
      patients compared to healthy individuals (TNFalpha: 2,336 +/- 346 and 2,192 +/-
      398 versus 1,218 +/- 224 pg/106 white blood cells [WBC]; IL-1Ra: 2,410 +/- 284
      and 2,326 +/- 186 versus 1,678 +/- 219 pg/106 WBC). Likewise, spontaneous
      production of TNFalpha, but not IL-1Ra, was higher in online HDF and low-flux HD
      patients than in normal controls (37 +/- 32 and 22 +/- 19 versus 0.8 +/- 0.3 pg
      TNFalpha/106 WBC). There was no difference in spontaneous and LPS-stimulated
      cytokine release between both dialysis groups. In addition, intradialytic
      cytokine induction was not significant for either treatment modality as
      spontaneous and LPS-stimulated cytokine release were not increased postdialysis.
      These findings indicate that online HDF does not contribute to chronic leukocyte
      activation and, consequently, does not place ESRD patients at greater risk with
      respect to inflammatory morbidity and mortality.

PMID- 10916062
TI  - Design of a fluidized bed bioartificial liver.
AB  - The aim of this study was to design a bioreactor for extracorporeal liver supply
      containing alginate beads in a fluidized bed regimen. The objective was to
      achieve a satisfactory mixing into the bioreactor to promote the potential
      exchanges and mass transfers. First, we checked whether both present phases
      (solid: alginate beads; liquid: saline solution at 20 degrees C) might allow for
      this fluidization. Then the optimal design was defined as a function of the
      required operating conditions, bead volume, and perfusion flow rate; the
      bioreactor cross section and height especially needed to be adjusted. The
      efficient fluidization, under optimized conditions, was proven through the follow
      up of the head losses generated by the fluidized bed. Criteria for scaling up
      were also determined.

PMID- 10916063
TI  - Particle release in extracorporeal low-density lipoprotein lowering therapies.
AB  - Release of microparticles into the blood during extracorporeal circulation must
      be kept low because of possibly serious acute and chronic adverse effects.
      Concentration and size distribution of microparticles were measured during
      simulated treatments (n = 7) on original equipment for 2 standard low-density
      lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel,
      Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to
      hemofiltration solutions. For both systems as well as in hemofiltration
      solutions, the mean particle concentrations in 500 ml portions gathered from the
      efferent blood line stayed below 10% of pharmacopoeia standards for infusion
      solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured
      size classes. Although particle concentrations were comparable in all systems,
      the mean total number of particles > or =2 microm released per session was lowest
      in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration
      solutions (2,240,000). This was mainly due to different total processed blood
      volumes necessary to achieve the required LDL reduction.

PMID- 10916065
TI  - Electrolyzed strong acid aqueous solution irrigation promotes wound healing in a
      burn wound model.
AB  - The purpose of the study was to understand the effectiveness of electrolyzed
      strong acid aqueous solution (ESAAS) for acceleration of epithelialization in a
      rat burn wound model. Eighteen anesthetized Sprague-Dawley rats received 30%
      total body surface area third-degree burns, and 2 days after injury, the wound
      eschars were removed. Rats were divided into 3 groups: Group 1, no irrigation;
      Group 2, irrigation with physiological saline; and Group 3, irrigation with
      ESAAS. Wounds were observed macroscopically until they were fully epithelialized,
      and epithelialized wounds were examined microscopically. Epithelialization of the
      wounds occurred significantly early in the rats treated with ESAAS (p < 0.05).
      Proliferation of associated lymphocytes and macrophages was more extensive in all
      rats that underwent irrigation than it was in control rats. ESAAS irrigation may
      promote tissue growth in burn wounds.

PMID- 10916064
TI  - Biostability, inflammatory response, and healing characteristics of a
      fluoropassivated polyester-knit mesh in the repair of experimental abdominal
      hernias.
AB  - The present study was undertaken to validate the benefits of a fluoropolymer
      treatment on the biostability, inflammatory response, and healing characteristics
      of a polyester mesh used for hernia repair, the Fluoromesh, as compared to a
      commercial monofilament-knit polypropylene mesh, Marlex, used as the control.
      Both were implanted for the repair of surgically induced abdominal hernias in
      piglets for prescheduled durations of implantation of 4, 15, and 60 days. The
      mesh and surrounding tissue were harvested at the sacrifice for the bursting
      strength and inflammatory response measurements in terms of alkaline and acid
      phosphatase secretion in the tissue, and for histological observations of the
      healing sequence and tissue thickness measurements by histomorphometric
      techniques. After cleaning to remove adherent tissue, the presence of the
      fluoropolymer at the surface of the mesh was detected using SEM and ESCA. The
      results demonstrated greater mechanical reinforcement and tissue development for
      the Fluoromesh than for the polypropylene mesh. The healing performance of the
      Fluoromesh was attributed to a more intense chronic inflammatory reaction early
      after implantation that stimulated significantly greater tissue ingrowth and
      integration. The concentration of fluoropolymer at the surface of the mesh was
      masked as a result of biological species adsorption. Textile analysis revealed
      that the Fluoromesh was dimensionally more stable in vivo than the polypropylene
      control mesh, which demonstrated stretching in the weft direction and shrinking
      in the warp direction during implantation.

PMID- 10916066
TI  - Effects of new polymer-coated extracorporeal circuits on biocompatibility during
      cardiopulmonary bypass.
AB  - An inflammatory response due to bioincompatibility of extracorporeal circuits is
      a major clinical issue during cardiopulmonary bypass (CPB). By using a swine
      model, we determined whether new polymer-coated circuits, the blood-contacting
      surfaces of which are coated with poly(2-methoxyethylacrylate) (PMEA), would
      reduce the inflammatory response during CPB. Plasma bradykinin levels and the
      percentages of CD35-positive monocytes in PMEA-coated circuits were significantly
      lower than those in uncoated circuits during CPB. The amount of proteins adsorbed
      on the PMEA-coated circuits was significantly lower than that on the uncoated
      circuits (0.30 microg/cm2 versus 3.42 microg/ cm2). Almost no IgG, IgM, or C3c/d
      was detected in proteins adsorbed on the PMEA-coated circuits although these
      proteins were clearly detected in proteins adsorbed on the uncoated circuits. We
      concluded that PMEA coating could reduce complement activation during CPB by
      suppressing the adsorption of IgG and IgM, which activate C3 via the classical
      pathway, on the surface of the circuits.

PMID- 10916067
TI  - Calcification of leaflets from porcine aortic valves crosslinked by ultraviolet
      irradiation.
AB  - Glutaraldehyde (GA)-pretreated porcine aortic valves are generally used as a
      bioprosthetic valve, but gradual calcification of the leaflets often occurs. It
      has been hypothesized that the crosslinking agent, GA, stabilizes and perhaps
      modifies phosphorus-rich calcifiable structures in the bioprosthetic tissue. This
      is supported by our findings that calcium deposition is induced rapidly in GA
      pretreated leaflets in comparison with ultraviolet (UV) irradiated leaflets.
      After 3 days of in vitro calcification test, calcium levels were 257.6 +/- 23.5
      microg/cm3 in GA-pretreated, 57.7 +/- 10.2 microg/cm3 in the control, and 108.6
      +/- 7.6 microg/cm3 in 24 h UV irradiated leaflets. The calcium level in all test
      groups increased as time proceeds and the calcium level of GA-pretreated leaflets
      was significantly higher than the control and UV irradiated leaflets during test.
      This rapid calcium deposition on the GA-pretreated leaflets may be due to
      residual aldehyde groups after pretreatment. The exposure time of UV irradiation
      was not significantly correlated with the extent of calcification. After 14 days
      of the test, calcium levels in leaflets UV irradiated for 1, 2, 4, and 24 h were
      502.6 +/- 12.3 microg/cm3, 547.5 +/- 34.1 microg/cm3, 564.3 +/- 26.1 microg/cm3,
      and 543.0 +/- 55.5 microg/cm3. In all test groups, [Ca]/[P] molar ratio decreased
      toward that of hydroxyapatite as the predominant mineral phase as time proceeds.
      This study suggests that UV irradiation can be considerable as an efficient
      crosslinking method to surmount the side effects induced by GA-pretreatment and
      may endow tissue with mechanical property.

PMID- 10916068
TI  - Flow characteristics past jellyfish and St. Vincent valves in the aortic position
      under physiological pulsatile flow conditions.
AB  - Thrombus formation and hemolysis have been linked to the dynamic flow
      characteristics of heart valve prostheses. To enhance our understanding of the
      flow characteristics past the aortic position of a Jellyfish (JF) valve in the
      left ventricle, in vitro laser Doppler anemometry (LDA) measurements were carried
      out under physiological pulsatile flow conditions. The hemodynamic performance of
      the JF valve was then compared with that of the St. Vincent (SV) valve. The
      comparison was given in terms of mean systolic pressure drop, back flow energy
      losses, flow velocity, and shear stresses at various locations downstream of both
      valves and at cardiac outputs of 3.5 L/min, 4.5 L/min, and 6.5 L/min
      respectively. The results indicated that both valves created disturbed flow
      fields with elevated levels of turbulent shear stress as well as higher levels of
      turbulence in the immediate vicinity of the valve and up to 1 diameter of the
      pipe (D) downstream of the valve. At a location further downstream, the JF valve
      showed better flow characteristics than the SV in terms of velocity profiles and
      turbulent shear stresses. The closure volume of the SV valve was found to be 2.5
      times higher than that of the JF valve. Moreover, the total back flow losses and
      mean systolic pressure drop also were found to be higher in the SV than the JF
      valve.

PMID- 10916069
TI  - Diameter of inferior caval vein and impedance analysis for assessment of
      hydration status in peritoneal dialysis.
AB  - In 19 stable peritoneal dialysis (PD) patients, hydration status was evaluated by
      measurement of vena cava diameter (VCD) and bioelectrical impedance analysis
      (BIA) variables: intracellular water (ICW), extracellular water (ECW), and total
      body water (TBW). We investigated whether BIA can replace VCD. VCD did not
      correlate with TBW but correlated moderately with ECW/TBW (r = 0.42; 0.025 < p <
      0.05) and ICW/ECW (r = -0.47; p < 0.025). Patients with underhydration (n = 4;
      VCD <8 mm/m2) revealed limits for BIA variables as ICW/ECW (>1.50) and ECW/TBW
      (<0.40). The same held true for overhydration (n = 5; VCD >11.5 mm/m2): ICW/ECW
      (<1.50) and ECW/TBW (>0.40). Although the positive predictive value of ICW/ECW
      and ECW/TBW for both under- and overhydration was only 50% and 54%, respectively,
      there were no false negative values. Although BIA cannot replace VCD in PD
      patients, the reverse holds true as well. Combining BIA and VCD may lead to a
      better estimation of hydration status because both techniques provide
      complementary information.

PMID- 10916070
TI  - Adsorption of microorganism components by lixelle beads.
AB  - We reported previously that Lixelle, which was used for beta-2 microglobulin
      (BMG) adsorption columns, could adsorb not only BMG but also inflammatory
      cytokines. We then were interested in the application of Lixelle to patients with
      systemic inflammatory response syndrome (SIRS) and tried to find out its ability
      to adsorb microorganism components in vitro using lipopolysaccharide (LPS) (E.
      coli: B8), endotoxin (ET) containing water, and peptidoglycan (PG: Micrococcus
      luteus). The initial concentrations of each solution were LPS (ET: 29,135 EU/L),
      contaminated water (ET: 3,523 EU/L), and PG (67.1 ng/ml) and 2.5 ml of each of
      the stock solutions and adjusted diluted solutions contained 0.5 ml of Lixelle
      beads. After shaking at 37 degrees C for 2 h, ET in the solutions was determined
      by the ET specific-limulus amebocyte lysate (ES-LAL) method and PG by the
      silkworm larbae plasma (SLP) method. The results revealed that even when ET
      concentrations in LPS and contaminated water were high, the samples containing
      Lixelle beads showed significant decreases. There was some adsorption of PG but
      no significant differences. Thus, Lixelle beads can adsorb not only BMG but also
      microorganism components such as ET and PG. These findings, together with the
      ability to adsorb inflammatory cytokines by Lixelle, show the possibility of
      application for the treatment of infectious SIRS.

PMID- 10916071
TI  - Analysis of the arterial blood pressure waveform using Fast Fourier Transform
      technique during left ventricular nonpulsatile assistance: in vitro study.
AB  - The arterial blood pressure waveform is variable during left ventricular
      assistance. The aim of this study is to examine the correlation between the left
      ventricular assist device (LVAD) condition and the arterial blood pressure
      waveform in a fixed cardiac output condition using a mock circuit. This mock
      circulation loop was composed of an aortic compliance chamber, a left atrial
      compliance chamber, a pneumatic pulsatile pump as a native heart, and a rotary
      blood pump representing the LVAD with left atrial drainage. The Fast Fourier
      Transform technique was utilized to analyze the arterial blood pressure waveform
      and calculate the pulsatility index (PI) and the pulse power index (PPI). The PI
      and PPI decreased with the increase of the LVAD rotational speed, exponentially.
      There was a significant negative correlation between the PI, PPI, and the LVAD
      rotational speed, flow rate, and assist ratio. The best correlation was observed
      between the PPI and the assist ratio (r = 0.986). From this viewpoint, an ideal
      LVAD condition may be estimated from the pulsatility change of the arterial blood
      pressure waveform.

PMID- 10916072
TI  - Living unrelated donor kidney transplantation.
AB  - BACKGROUND: Living unrelated donors remain an underutilized resource, despite
      their high graft survival rates. In this article, we updated the long-term
      results of more than 2500 living unrelated donor transplants performed in the
      United States. METHODS: Between 1987 and 1998, 1765 spouse, 986 living unrelated,
      27,535 living related, and 86,953 cadaver donor grafts were reported to the
      United Network for Organ Sharing Kidney Registry. Kaplan-Meier curves compared
      graft survival rates in stratified analyses, and a log-linear analysis adjusted
      donor-specific outcomes for the effects of 24 other transplant factors. RESULTS:
      The long-term survival rates for both spouse and living unrelated transplants
      were essentially the same (5-year graft survivals of 75 and 72% and half-lives of
      14 and 13 years, respectively). The results were similar to that for parent donor
      grafts (5-year graft survival = 74% and half-life = 12 years) and were
      significantly (P = 0.003) better than cadaver donor grafts (5-year graft survival
      = 62% and half-life = 9 years). After adjusting for the presence of transplant
      factors known to influence survival rates, recipients of living unrelated donor
      kidney transplants still had superior outcomes compared with cadaver transplants.
      CONCLUSIONS: Living unrelated kidney donors represent the fastest growing donor
      source in the United States and provide excellent long-term results. Encouraging
      spouses to donate could remove nearly 15% of the patients from the UNOS waiting
      list, effectively increasing the number of available cadaveric organs.

PMID- 10916073
TI  - A molecular and genetic view of human renal and urinary tract malformations.
AB  - Malformations of the kidney and lower urinary tract are common causes of chronic
      renal failure in infants and young children, but little is known about the
      molecular pathogenesis of these disorders. In animal experiments, the main causes
      of malformation are mutations, chemical and pharmaceutical teratogens,
      obstruction of fetal urinary flow, and alterations of maternal nutrition. The
      focus of this review is to consider how mutations and other alterations of gene
      expression during development cause human urinary tract malformations. Some of
      these disorders are associated with congenital anomalies in multiple organ
      systems, and two such syndromes are considered in detail: first, the renal
      coloboma syndrome, in which mutations of the PAX2 transcription factor cause
      partial failure of urinary tract growth; second, Kallmann's syndrome, in which
      mutations of a cell-signaling molecule are associated with the absence of the
      urinary tract. In patients seen by nephrologists and urologists, however, most
      urinary tract malformations occur in isolation, and in some of these individuals,
      a genetic pathogenesis is strongly suggested by a positive family history and
      genetic linkage studies. One common example is primary vesicoureteric reflux.
      Furthermore, sporadic malformations have been shown to be associated with
      polymorphisms of genes expressed during construction of the urinary tract. In the
      long term, an understanding of the genetic aspects of human urinary tract
      malformations will help to unravel the pathogenesis of these disorders and may
      facilitate the design of genetic screening tests with a view to early diagnosis.

PMID- 10916074
TI  - Angiotensin I-converting enzyme gene insertion/deletion and angiotensinogen M235T
      polymorphisms: risk of chronic renal failure. End-Stage Renal Disease Study
      Group.
AB  - BACKGROUND: Chronic renal failure (CRF) is a complex phenotype that results from
      an underlying kidney disease and superimposing environmental and genetic factors.
      The aim of our study was to evaluate the role of polymorphisms in the genes
      encoding for components of the renin-angiotensin system (RAS) in the development
      and/or progression of CRF. METHODS: Two hundred forty-seven family trios
      (patients with CRF and both parents; 120 with primary chronic glomerulonephritis,
      80 with interstitial nephritis, and 47 with type 1 diabetes with nephropathy)
      were examined, and transmission/disequilibrium test (TDT) was used to evaluate
      allele transmission from heterozygous parents to affected offspring. RESULTS: The
      D allele of the angiotensin I-converting enzyme (ACE) gene insertion/deletion
      polymorphism was transmitted significantly more frequently than expected for no
      association among all examined trios and in the subgroup of patients with
      interstitial nephritis. The angiotensinogen 235T allele was transmitted
      significantly more frequently to patients with CRF than expected for no
      association, but the effect was seen only in patients with interstitial
      nephritis. The presence of the DD or ID genotype was associated with a faster
      rate of decline of renal function, which was not observed for the angiotensinogen
      M235T polymorphism. For chymase gene and angiotensin II receptor type 1 gene,
      allele transmission did not deviate significantly from a random proportion of
      50:50%. CONCLUSIONS: The results of this study suggest that ACE gene
      insertion/deletion and angiotensinogen M235T polymorphisms contribute to the
      increased risk for the development of CRF, but the magnitude of the effect within
      subsets of patients with specific etiologies of CRF must be evaluated further.

PMID- 10916075
TI  - Clinical and genetic studies of CLCN5 mutations in Japanese families with Dent's
      disease.
AB  - BACKGROUND: Dent's disease is an X-linked renal tubular disorder that is
      characterized by low molecular weight proteinuria, hypercalciuria,
      nephrolithiasis, and renal failure. The disease is caused by inactivation of a
      renal chloride channel gene, CLCN5, that encodes a 746-amino acid protein with 12
      to 13 transmembrane domains. The Japanese variant of Dent's disease has been
      observed to be less severe, and we have investigated two unrelated Japanese
      families for CLCN5 mutations. METHODS: Six patients from two unrelated families
      were studied. Leukocyte DNA from probands was used with CLCN5-specific primers
      for polymerase chain reaction (PCR) amplification of the coding region and exon
      intron boundaries, and the DNA sequences of the products were determined to
      identify abnormalities in the gene. RNA extracted from the kidney, leukocytes, or
      urine sediments was used to characterize further the effects of the identified
      mutations. RESULTS: beta2-microglobulinuria was detected in five patients,
      hypercalciuria in two patients, nephrolithiasis in three patients (2 of whom were
      females), and one 51-year-old man had renal failure. Two novel CLCN5 mutations
      consisting of an a to g transition at the invariant ag acceptor splice site of
      intron 5 and an intragenic deletion that encompassed the region between intron 3
      and intron 6 were identified. The acceptor splice site mutation led to the
      utilization of two alternative cryptic splice sites in exon 6 that resulted in a
      frameshift or skipping of the exon 6. The deletional mutation, which resulted in
      a loss of exons 4, 5, and 6, is predicted to lead to a loss of domains 1 through
      4. Both mutations predict truncated chloride channels that are likely to result
      in a functional loss. CONCLUSIONS: The observations of renal failure in one male
      and nephrolithiasis in two females represent important new findings in this
      Japanese variant of Dent's disease that is associated with CLCN5 mutations. In
      addition, our study is the first to demonstrate the use of urinary sediment cells
      and renal tissue for the detection of CLCN5 transcript abnormalities. These
      results help to expand the spectrum of CLCN5 mutations associated with Dent's
      disease.

PMID- 10916077
TI  - A DNA element in the alpha1 type III collagen promoter mediates a stimulatory
      response by angiotensin II.
AB  - BACKGROUND: Angiotensin II (Ang II) plays an important role in extracellular
      matrix deposition and tissue scarring in the kidney and the heart. The mechanism
      for extracellular matrix stimulation by Ang II is currently hypothetical, with
      one possibility pointing to a direct effect on cell synthesis of specific
      collagens. METHODS: We studied the molecular mechanism for activation of type III
      collagen synthesis by Ang II in an in vitro cell model of myofibroblasts by
      evaluating (1) alpha1(III) collagen mRNA expression; (2) alpha1(III) collagen
      promoter activity; (3) DNA/protein binding with characterization of binding
      sites; (4) expression of transcription factors; and (5) the role of a short DNA
      segment as Ang II responsive element. RESULTS: We found a specific dose-dependent
      stimulation of alpha1(III) collagen mRNA expression and a parallel effect on
      alpha1(III) collagen promoter activity. Transfection of constructs containing
      alpha1(III) collagen promoter fragments of different lengths localized the site
      of activation within the shortest 178 bp construct. By gel-retardation
      experiments, we observed the formation of a DNA-protein complex with crude
      extracts from Ang II-stimulated cells and an oligonucleotide spanning the 3 to 20
      sequence. This complex was due to a sequence-specific interaction and was
      abolished by a 3 bp substitution mutation. The introduction of this mutation into
      the 178 bp construct abolished the stimulatory effect of Ang II. CONCLUSIONS:
      These results demonstrate that Ang II stimulates the expression of alpha1(III)
      collagen mRNA in myofibroblasts in vitro by activating the alpha1(III) collagen
      promoter at the level of a factor recognition site localized immediately
      downstream of the transcription start site. This mechanism could be involved in
      Ang II-induced renal and heart fibrosis.

PMID- 10916076
TI  - Altered gene expression in kidneys of mice with 2,8-dihydroxyadenine
      nephrolithiasis.
AB  - BACKGROUND: We have developed a knockout mouse model for adenine
      phosphoribosyltransferase (APRT) deficiency, a condition that often leads to 2,8
      dihydroxyadenine (DHA) nephrolithiasis in humans. Aprt knockout male mice develop
      severe renal damage by three months of age, but this is strain specific. Renal
      damage in female mice is less pronounced than in males. The gene level changes
      that promote renal injury in APRT-deficient mice are not known. METHODS: We used
      mRNA differential display polymerase chain reaction (DD-PCR) to analyze renal
      gene expression changes in APRT-deficient male and female mice (strain C3H)
      compared with age- and sex-matched Aprt heterozygote controls. The differentially
      amplified bands were reamplified, cloned, sequenced, and queried against the
      National Center for Biotechnology Information nonredundant databases using the
      Basic Alignment Search Tool. Relative quantitative reverse transcription
      polymerase chain reaction was used to confirm the results of DD-PCR for a
      selected number of genes in one-, three-, and six-month-old male and female mice.
      RESULTS: Sixty-three differentially amplified bands were identified, including 21
      for known genes, and 8 of these were examined further. In three-month-old APRT
      deficient male mice, the expression of C10 was increased tenfold, and there was a
      fourfold to sevenfold increase in the expression of a disintegrin and
      metalloproteinase with thrombospondin motifs (ADAMTS-1), MGP (matrix Gla
      protein), and lysyl oxidase (LOX). The expression of cholecystokinin-A receptor
      (CCKAR), imprinted multimembrane-spanning polyspecific transporter-like gene 1
      (IMPT-1), and kidney androgen-regulated protein (KAP) was diminished twofold to
      fourfold, but there was little or no change in the expression of organic anion
      transporter (OATP). Except for a more than tenfold increase in C10 expression and
      up to tenfold decrease in KAP expression, APRT-deficient female mice did not show
      significant changes in gene expression compared with controls. CONCLUSIONS: These
      findings suggest that (1) there are sex-related differences in gene expression in
      DHA lithiasis, possibly caused by increased deposition of DHA crystals in male
      compared with female kidneys; and (2) the expression of certain genes (for
      example, C10) may simply be an indication of nonspecific cellular stimulation and
      may not be related to renal injury.

PMID- 10916078
TI  - Angiotensin II-induced growth of vascular smooth muscle cells requires an Src
      dependent activation of the epidermal growth factor receptor.
AB  - BACKGROUND: Angiotensin II (Ang II) is a potent stimulus of vascular smooth
      muscle cell (VSMC) growth. Activation of extracellular signal-regulated kinase
      (ERK), the archetypal mitogen-activated protein (MAP) kinase, and
      phosphatidylinositol 3 (PI3) kinase are critical steps in Ang II-induced
      mitogenic signaling. However, the mechanism involved in the activation of these
      kinases upon binding of Ang II to its receptor is poorly understood. METHODS: In
      the present study, we examined the role of the epidermal growth factor receptor
      (EGFR) in Ang II signaling in VSMCs employing immunoprecipitation, Western blot
      analysis, kinase immunocomplex assay, and [3H]-thymidine incorporation. RESULTS:
      A time-dependent tyrosine phosphorylation of the EGFR in response to Ang II was
      observed that was mediated by the Ang II type 1 receptor. This transactivation of
      the EGFR was blocked in the presence of PP1, an inhibitor of the intracellular
      Src-like tyrosine kinases. The tyrphostin AG 1478, a selective EGFR antagonist,
      inhibited both Ang II- and EGF-induced tyrosine phosphorylation of the EGFR.
      Furthermore, Ang II induced the binding of the adaptor protein Shc to the EGFR,
      leading to phosphorylation of Shc. In addition, the same nanomolar concentrations
      of AG 1478 that were effective in EGF signaling blocked the Ang II-induced
      activation of ERK and PI3 kinase in a dose-dependent manner. Proliferation of
      VSMCs, detected by measurements of DNA synthesis, following stimulation with Ang
      II was potently inhibited in the presence of AG 1478 or PP1. CONCLUSION: Our data
      suggest that EGFR serves as a role in mitogenic signaling following stimulation
      with Ang I through a ligand-independent and Src-dependent transactivation of the
      EGFR. Furthermore, we demonstrate this transactivation as a pivotal step in Ang
      II-induced activation of MAP kinase and PI3 kinase, as well as growth of VSMCs.

PMID- 10916079
TI  - Identification of 25-hydroxyvitamin D3 1alpha-hydroxylase gene expression in
      macrophages.
AB  - BACKGROUND: The 25-hydroxyvitamin D3 1alpha-hydroxylase (1alpha-hydroxylase) is
      almost exclusively expressed in the kidney. However, 1alpha-hydroxylase
      activities have been observed in some extrarenal tissues, including inflammatory
      cells of the monocyte/macrophage lineage. In sarcoidosis, macrophage 1alpha
      hydroxylase causes overproduction of 1,25-(OH)2D3, resulting in hypercalcemia. In
      this study, we investigated the regulation of macrophage 1alpha-hydroxylase at a
      molecular level. METHODS: We used the human monocytic cell line THP-1, which can
      be differentiated into macrophage-like cells by treatment with phorbol ester. The
      expression of 1alpha-hydroxylase in THP-1 cells was examined by Northern blotting
      and immunoblotting using an antibody raised against a synthetic peptide
      corresponding to the 14 C-terminal amino acids of 1alpha-hydroxylase. We
      investigated the regulation of 1alpha-hydroxylase mRNA expression by RNase
      protection assay. RESULTS: Northern blot and immunoblot analyses confirmed the
      expression of 1alpha-hydroxylase in THP-1 cells at the mRNA and protein levels.
      Although parathyroid hormone and calcitonin, known stimulators of renal 1alpha
      hydroxylase, did not affect the expression of 1alpha-hydroxylase mRNA, 8-Br-cAMP
      (5 x 10-4 mol/L) increased the expression of 1alpha-hydroxylase mRNA in THP-1
      cells (198 +/- 9%). 1,25-(OH)2D3, known as a suppressor of renal 1alpha
      hydroxylase, did not affect the expression of 1alpha-hydroxylase mRNA. By
      contrast, 1,25-(OH)2D3 markedly increased the expression of 25-hydroxyvitamin D3
      24-hydroxylase mRNA. Interferon-gamma (2000 IU/mL) increased the expression of
      1alpha-hydroxylase mRNA in differentiated THP-1 cells (922 +/- 25%). CONCLUSIONS:
      The present results suggest that 1alpha-hydroxylase activity in macrophages is
      mediated by the same enzyme as in kidney. Interferon-gamma treatment increases
      macrophage 1alpha-hydroxylase levels via directly increasing gene expression of
      this enzyme.

PMID- 10916080
TI  - Impact of uremia on female reproductive cyclicity, ovulation, and luteinizing
      hormone in the rat.
AB  - BACKGROUND: Impaired reproductive function accompanies chronic renal
      insufficiency (uremia) in both the human and experimental animal. Clinical
      hypogonadism occurs in both genders. The present studies were designed to
      investigate possible anti-ovulatory effects of uremia in the female rat, a
      species that produces multiple ova during the normal estrous cycle. METHODS:
      Renal insufficiency (uremia) was induced by 5/6 nephrectomy. Two control groups
      comprised sham-operated animals fed ad libitum (sham) or pair-wise with the
      uremic animals (pair-fed). Estrous cycles were determined by cytology of vaginal
      lavage. We examined concomitant changes in the preovulatory luteinizing hormone
      (LH) surge by radioimmunoassay (RIA), immunoradiometric assay (IRMA), and
      bioassay. Repetitive LH measurements were made from blood samples taken by intra
      atrial catheter throughout the afternoon and evening of proestrus. The following
      morning (estrus), ovaries were collected, and ova were enumerated per oviduct.
      RESULTS: Experimentally uremic animals manifested a threefold elevation of plasma
      creatinine and urea nitrogen and concomitantly a more than 50% impoverishment of
      ova production. Analyses of a large group of animals (N = 83) by RIA revealed
      uremia-associated attenuation of the preovulatory LH surge. Further measurements
      of the preovulatory LH surge by independent IRMA and LH bioassay (N = 26)
      corroborated this attenuation. Additional experiments indicated that these
      hormonal changes, but not changes in ovulation, might further reflect modulation
      of LH release by the anesthesia used in the preparative nephrectomy and
      catheterization surgeries. When normalized to body weight, the ovaries of uremic
      rats were found to weigh more than those of either the sham or pair-fed animals.
      CONCLUSIONS: The present experiments take advantage of an experimental uremic
      model to document a consistent decrease in the number of ova released during
      estrus in the uremic animal. Possible disruption of hypothalamic-pituitary
      ovarian regulation is further highlighted by attenuation in the preovulatory LH
      surge. These results provide a basis for further studies of neuroendocrine
      pathophysiology in a rodent model of uremia-associated ovulatory disruption.

PMID- 10916081
TI  - Zinc deficiency further increases the enhanced expression of endothelin-1 in
      glomeruli of the obstructed kidney.
AB  - BACKGROUND: Zinc (Zn) is an essential trace element in humans and animals. We
      have recently documented that Zn deficiency may aggravate tubulointerstitial
      nephropathy seen in the obstructed kidney (OK) of 72 hours duration through a
      further increase in the activity of endogenous angiotensin II in the OK. Also, it
      is known that the vasoconstrictors angiotensin II and endothelin (ET)-1 may be
      implicated in the deterioration of glomerular hemodynamics caused in the OK. We
      therefore designed the present study to examine the effect of Zn deficiency on
      the expression of ET-1 and a potential role of endogenous angiotensin II in the
      expression of ET-1 in glomeruli of the OK of 72 hours duration. METHODS: Using
      reverse transcription-polymerase chain reaction and immunohistochemistry, the
      expression of prepro-ET-1 mRNA and ET-1 was examined in glomeruli of the
      contralateral, non-obstructed control kidney (CLK) and the OK from rats with
      unilateral ureteral obstruction (UUO) of 72 hours duration fed a standard or a Zn
      deficient diet for approximately 50 days. The rats in each group were treated
      with saline alone or the angiotensin-converting enzyme inhibitor enalapril before
      and after ureteral obstruction. RESULTS: The expression of prepro-ET-1 mRNA and
      ET-1 was markedly greater in the OK than in the CLK in the standard and the Zn
      deficient diet groups. However, the expression of prepro-ET-1 mRNA and ET-1 was
      substantially increased in the OK of the Zn-deficient diet group relative to the
      OK of the standard diet group. There were no significant differences in the
      expression of prepro-ET-1 mRNA and ET-1 between the CLK of the two diet groups.
      Administration of enalapril restored the expression of prepro-ET-1 mRNA and ET-1
      in the OK to levels seen in the CLK in the standard and the Zn-deficient diet
      groups. Enalapril produced no effects on the expression of prepro-ET-1 mRNA and
      ET-1 in the CLK of the two diet groups. CONCLUSIONS: UUO of 72 hours duration may
      increase the expression of prepro-ET-1 mRNA and ET-1 in glomeruli of the OK
      through an increment in the biological action of endogenous angiotensin II in the
      OK. Moreover, Zn deficiency may enhance the expression of prepro-ET-1 mRNA and ET
      1 in glomeruli of the OK through a further increment in the biological action of
      endogenous angiotensin II in the OK. Zn deficiency appears to be a factor to
      worsen glomerular hemodynamics in the OK of the UUO setting of 72 hours duration
      through an increment in the biological action of the vasoconstrictors angiotensin
      II and ET-1.

PMID- 10916082
TI  - Progressive renal fibrosis in murine polycystic kidney disease: an
      immunohistochemical observation.
AB  - BACKGROUND: The appearance of interstitial fibrosis in polycystic kidneys is
      emblematic of progressive disease. Matrix forming this scar tissue is derived
      from local renal cells in response to cystogenesis. We investigated the phenotype
      of collagen-producing cells in the cystic kidneys of DBA/2-pcy mice to better
      characterize the spectrum of interstitial cells associated with renal
      fibrogenesis. METHODS: The extent of interstitial fibrosis and the number of
      fibroblasts in cystic kidneys were first quantitated over time using computer
      assisted image analysis. Subsequently, antisera to four cell protein markers were
      studied by coexpression immunohistochemistry during progression of fibrosis using
      confocal microscopy. The antisera included fibroblast-specific protein 1 (FSP1)
      for fibroblast phenotype, alpha-smooth muscle actin (alpha-SMA) for contractile
      phenotype, vimentin (VIM) for mesenchymal phenotype, and heat shock protein 47
      (HSP47) for interstitial collagen-producing phenotype. RESULTS: Interstitial
      fibrosis in cystic kidneys gradually increased throughout the 30-week observation
      period of our study. With progression of cystogenesis, most of the tubules in pcy
      mice either dilated or disappeared with time. FSP1+ fibroblasts were distributed
      sparsely throughout the renal interstitium of young pcy and wild-type mice. Their
      number increased in the widening fibrotic septa by 18 weeks of age and persisted
      through 30 weeks of the study interval. Some epithelia among remnant tubules
      trapped within fibrotic septa around adjacent cysts also acquired the phenotype
      of FSP1+, HSP47+ collagen-producing fibroblasts, suggesting a possible role for
      epithelial-mesenchymal transformation (EMT) in this process. Most FSP1+
      fibroblasts were alpha-SMA-, but HSP47+, suggesting they were producing collagen
      proteins for the extracellular matrix. alpha-SMA+, FSP1-, HSP47+ or HSP47- cells
      were also observed, and the latter tended to distribute independently in a linear
      pattern, reminiscent of vasculature adjacent to forming cysts. VIM+ expression
      was not observed in alpha-SMA+ cells. CONCLUSIONS: Many nonoverlapping as well as
      fewer overlapping populations of FSP1+ and alpha-SMA+ cells shared in the
      collagen expression associated with progressive fibrogenesis in pcy mice
      undergoing cystogenesis. Some FSP1+ fibroblasts are likely derived from tubular
      epithelium undergoing EMT, while alphaSMA+, VIM- cells probably represent
      vascular smooth muscle cells or pericytes surviving vessel attenuation during the
      chaos of fibrogenesis. Importantly, not all interstitial cells producing
      collagens are alpha-SMA+.

PMID- 10916083
TI  - Mesangial factor V expression colocalized with fibrin deposition in IgA
      nephropathy.
AB  - BACKGROUND: Factor V in its active form (Va) plays a key role at the termination
      of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for
      the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb)
      is often observed in mesangial areas in active types of human glomerulonephritis.
      In this study, to clarify contribution of factor V in intramesangial coagulation,
      mesangial factor V expression and its relationship to mesangial proliferation and
      fibrin deposition in IgA nephropathy (IgAN) were investigated. METHODS: Twenty
      two patients with IgAN were studied. XFb was detected in renal biopsy specimens
      using anti-d-dimer antibody combined with plasmin exposure, and factor V was
      detected with rabbit antibody against human factor V. Double-labeling
      immunohistochemistry was used to investigate the relationship of the glomerular
      distribution of factor V to XFb. The relationship of factor V staining to the
      activity index or XFb deposition was evaluated. The expression of factor V mRNA
      was assessed by in situ hybridization in relationship to the antigen staining of
      alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor
      V in glomeruli was studied by immunoelectron microscopy. RESULTS: XFb and factor
      V were observed in the mesangium and along capillary loops in seven and nine
      specimens, respectively. Factor V had intense, frequent expression in the
      proliferating and necrotizing areas, showing a significant relationship to XFb (P
      < 0.05). Furthermore, XFb deposition and factor V expression were markedly
      correlated with disease activity (P = 0.005 and P = 0.008, respectively). By
      double-labeling experiments, XFb and factor V were often seen colocalized in
      mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense
      cellular proliferation. By in situ hybridization, factor V mRNA was detected
      mainly in the mesangial cells, which were positive for alpha-SMA, and partly in
      the endothelial cells. By immunoelectron microscopy, factor V presence was
      confirmed in the mesangium and endothelium. CONCLUSION: The present findings
      suggest that factor V is strongly expressed in mesangial cells in active IgAN
      accompanied with mesangial proliferation and may exert procoagulant activity,
      leading to intramesangial coagulation.

PMID- 10916085
TI  - Interstitial fibrosis in mice with overload proteinuria: deficiency of TIMP-1 is
      not protective.
AB  - BACKGROUND: Progressive renal interstitial fibrosis is characterized by up
      regulated expression of the gene that encodes the tissue inhibitor of
      metalloproteinases-1 (TIMP-1), a regulator of extracellular matrix remodeling,
      suggesting that impaired matrix turnover contributes to the fibrogenic process.
      The present study was designed to develop a murine model of renal interstitial
      fibrosis, and to determine the functional significance of up-regulated Timp-1
      expression by comparing the severity of this renal disease in wild-type mice and
      mice genetically deficient in Timp-1. METHODS: Initial pilot studies developed
      and characterized a murine model of bovine serum albumin (BSA)-induced protein
      overload proteinuria with respect to the degree of proteinuria, severity of
      interstitial fibrosis, and renal mRNA levels for genes encoding matrix proteins,
      transforming growth factor-beta1 (TGF-beta1), and TIMP-1, -2, -3, and -4. In the
      final study, the severity of interstitial fibrosis was compared in wild-type and
      Timp-1-deficient mice after six weeks of proteinuria. RESULTS: Mice injected with
      large daily intraperitoneal doses of BSA developed proteinuria, interstitial
      inflammation, and progressive interstitial fibrosis. A time course study based on
      measurements after one, two, and six weeks of BSA injections showed increased
      renal mRNA levels for the matrix genes procollagens alpha1(I), alpha1(III), and
      alpha2(IV) and TGF-beta1 and Timp-1. Timp-2 and Timp-3 genes were constitutively
      expressed at high levels in the normal kidneys and showed little change in the
      proteinuric kidneys. Timp-4 transcripts were not detected in any of the kidneys.
      After six weeks of BSA overload-proteinuria, the groups (N = 8 per group) of wild
      type and Timp-1-deficient mice developed significant interstitial fibrosis
      compared with the control saline-injected groups. The severity of the
      interstitial fibrosis was similar in both proteinuric groups based on an
      assessment of the final kidney weight, total kidney collagen content, and the
      number of interstitial fields with increased fibronectin staining. CONCLUSIONS:
      Results of the present study indicate that TIMP-1 deficiency does not alter the
      degree of interstitial fibrosis in the murine overload proteinuria model.
      Potential explanations include Timp-1 genetic redundancy, as suggested by the
      observation that, despite significant intrarenal induction of the Timp-1 gene
      expression, net renal metalloproteinase-9 (MMP-9) activity was not significantly
      altered. TIMP-1 is a multifunctional protein that may play a metalloproteinase
      independent role in response to renal injury.

PMID- 10916084
TI  - Infection of mesangial cells with HIV and SIV: identification of GPR1 as a
      coreceptor.
AB  - BACKGROUND: Mesangial cells are an important component of the glomerulus.
      Dysfunction of mesangial cells is thought to be involved in the development of
      human immunodeficiency virus type 1 (HIV-1)-associated nephropathy (HIVAN). HIVAN
      is a structural renal failure frequently observed in patients with acquired
      immune deficiency syndrome. However, the susceptibility of mesangial cells to HIV
      1 is disputable. More than ten G protein-coupled receptors, including chemokine
      receptors, have been shown to act as HIV-1 coreceptors that determine the
      susceptibilities of cells to HIV-1 strains with specific cell tropisms. METHODS:
      We examined the susceptibility of mesangial cells to various HIV-1, HIV type 2
      (HIV-2) and simian immunodeficiency virus (SIV) strains. Expression of CD4 and
      HIV/SIV coreceptors was examined by Western blotting and polymerase chain
      reaction. RESULTS: Mesangial cells were found to be susceptible to HIV-1 variant
      and mutants that infect brain-derived cells, but highly resistant to T-tropic
      (X4), M-tropic (R5) or dual-tropic (X4R5) HIV-1 strains. In addition, mesangial
      cells were also susceptible to HIV-2 and SIV strains that infect the brain
      derived cells. Among HIV/SIV coreceptors we tested, the expression of GPR1 mRNA
      was detected in mesangial cells. Expression of CD4 mRNA and protein was also
      detected in them. Mesangial cells and GPR1-transduced CD4-positive cells showed
      similar susceptibilities to the HIV-1 variant and mutants and HIV-2 and SIV
      strains. CONCLUSIONS: CD4 and GPR1 mRNAs were detected in mesangial cells.
      Mesangial cells were susceptible to HIV/SIV strains that use GPR1 as a
      coreceptor. Our findings suggest that an orphan G protein-coupled receptor, GPR1,
      is a coreceptor expressed in mesangial cells. It remains to be investigated
      whether the interaction of mesangial cells with specific HIV-1 strains through
      GPR1 plays a role in the development of HIVAN.

PMID- 10916086
TI  - Immunoglobulins in chronic renal failure of childhood: effects of dialysis
      modalities.
AB  - BACKGROUND: It is not clear whether low serum levels of IgG (subclasses),
      previously demonstrated in children on peritoneal dialysis (PD), are related to
      the PD procedure or to factors associated with chronic renal failure (CRF). The
      aim of our study was to analyze the effect of PD on serum and PD effluent (PDE)
      IgG and subclass levels in children with end-stage renal failure. METHODS: We
      measured albumin, IgG, IgA, IgM, and IgG subclasses in serum and PDE from
      children on PD (N = 40) and compared the serum values with those of children
      treated with hemodialysis (HD, N = 23) or presenting with CRF but not yet
      dialyzed (CRF; N = 63), and with a group of healthy controls (HCs; N = 67).
      Sixteen PD children could be followed sequentially from before starting PD and
      eight during a peritonitis episode. RESULTS: Forty percent of the PD children
      showed reduced serum IgG2 levels (P = 0.0003) compared with 35% in HD (P =
      0.006), 33% in CRF (P = 0.001), and 9% in HC children. IgG1 deficiencies were
      observed in 25% of PD patients (P < 0.0001), 4% of HD (P = NS), 16% of CRF (P =
      0.0005), and 0% of HC children. IgG3 and IgG4 deficiencies were observed less
      frequently. Peritoneal clearances were similar for total IgG, IgG1, IgG2, and
      IgG4, but were lower for IgG3 (P < 0.05). No relationships were found between
      clearances and age or duration of PD treatment. Total IgG (P = 0. 003) and IgG1
      (P = 0.002) levels declined just after starting PD. Peritonitis was associated
      with temporarily increased peritoneal loss of Ig, while the serum concentrations
      were unaffected. No significant relationship was found between the peritonitis
      incidence and reduced IgG or subclasses. However, all children with two or more
      peritonitis episodes per year had a reduced Ig level. CONCLUSIONS: Although the
      mean serum concentrations of immunoglobulins were normal in all studied groups, a
      deficiency of one or more IgG subclasses was present in all groups with renal
      failure, suggesting inhibition of their synthesis by the uremic state. Ig
      deficiencies were more frequently found in PD, likely caused by protein loss in
      PDE. A high peritonitis incidence was associated with reduced serum Ig levels.

PMID- 10916087
TI  - Phospholipase A2 mediates immediate early genes in cultured renal epithelial
      cells: possible role of lysophospholipid.
AB  - BACKGROUND: Exposure to high levels of oxalate induces oxidant stress in renal
      epithelial cells and produces diverse changes in cell function, ranging from cell
      death to cellular adaptation, as evidenced by increased DNA synthesis, cellular
      proliferation, and induction of genes associated with remodeling and repair.
      These studies focused on cellular adaptation to this oxidant stress, examining
      the manner by which oxalate exposure leads to increased expression of immediate
      early genes (IEGs). Specifically, our studies assessed the possibility that
      oxalate-induced changes in IEG expression are mediated by phospholipase A2
      (PLA2), a common pathway in cellular stress responses. METHODS: Madin-Darby
      canine kidney (MDCK) cells were exposed to oxalate in the presence or absence of
      PLA2 inhibitors: mepacrine and arachidonyl trifluoromethyl ketone (AACOCF3).
      Expression of IEG (c-jun, egr-1, and c-myc) mRNA was assessed by Northern blot
      analysis. PLA2 activity was determined by measuring the release of
      [3H]arachidonic acid (AA) from prelabeled cells. RESULTS: Oxalate exposure (1 to
      1.5 mmol/L) induced time- and concentration-dependent increases in IEG mRNA.
      Treatment with mepacrine resulted in a 75 to 113% reduction of oxalate-induced c
      jun, egr-1, and c-myc mRNA, while AACOCF3 caused a 41 to 46% reduction of oxalate
      induced c-jun and egr-1 mRNA. Of the two major byproducts of PLA2, only
      lysophosphatidylcholine (20 micromol/L) increased c-jun and egr-1 mRNA. In
      contrast, AA (25 micromol/L) attenuated the oxalate-induced increase in c-jun and
      egr-1 mRNA, presumably by inhibiting PLA2 activity. CONCLUSIONS: These findings
      suggest that PLA2 plays a major role in oxalate-induced IEG expression in renal
      epithelial cells and that lysophospholipids might be a possible lipid mediator in
      this pathway.

PMID- 10916088
TI  - Erythropoietin stimulates proliferation of human renal carcinoma cells.
AB  - BACKGROUND: We reported recently that normal human, rat, and mouse tubular cells
      express authentic erythropoietin-receptors (EPO-R) through which EPO stimulates
      mitogenesis. The present study examines whether EPO could elicit such a
      proliferative and thereby potentially detrimental response in cells of human
      renal-cell carcinoma (RCC). METHODS: Nephrectomy samples were screened from
      patients with RCC (one chromophilic, two clear cell) as well as cell lines of
      human (Caki-2, 786-0) and mouse (RAG) renal adenocarcinomas for expression of EPO
      R transcripts and protein. Cells were further tested for specific 125I-EPO
      binding and mitogenic response to EPO. RESULTS: Authentic EPO-R transcripts and
      protein (approximately 72 kD) were detected in renal tumors and cell lines.
      Tumors showed low-level EPO expression, while cell lines did not. In cells,
      specific 125I-EPO binding to a single class of EPO-R (apparent Kd 1. 3 to 1.4
      nmol/L, Bmax 2.2 to 2.6 fmol/mg protein) was observed. EPO stimulated cell
      proliferation dose dependently, and the individual mitogenic effects of either
      EPO or 10% newborn calf serum were markedly amplified when both were
      coadministered. CONCLUSION: These data are the first to demonstrate, to our
      knowledge, that human RCCs express EPO-R message and protein and that receptor
      activation stimulates their proliferation in vitro. If these mitogenic effects of
      EPO are also operative in patients with RCC, endogenous EPO or its administration
      for the treatment of anemia could potentially hasten proliferation of
      renocellular malignancies.

PMID- 10916090
TI  - Differential expression of cyclin-dependent kinase inhibitors in human glomerular
      disease: role in podocyte proliferation and maturation.
AB  - BACKGROUND: Normal human podocytes are terminally differentiated and quiescent
      cells. It is not known why podocytes fail to proliferate in response to most
      forms of injury. Proliferation is regulated by cell cycle proteins and their
      inhibitors. The Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21,
      p27, p57) in general prevent proliferation by inhibiting cyclin-CDK complexes. In
      the current study, we determined the expression and possible role of specific CDK
      inhibitors in podocyte proliferation in human disease characterized by podocyte
      injury. METHODS: Immunostaining was performed for the CDK inhibitors p21, p27,
      and p57 and the proliferation marker Ki-67 on renal biopsies from patients with
      minimal change disease (MCD; N = 6), membranous glomerulopathy (MGN; N = 19),
      cellular variant of focal segmental glomerulosclerosis (FSGS; N = 12), collapsing
      glomerulopathy (CG; N = 9), and HIV-associated nephropathy (HIVAN; N = 16). Adult
      nephrectomy specimens without evidence of glomerular disease served as controls
      (N = 9). RESULTS: Normal quiescent podocytes express p27 and p57, but not p21. In
      diseases without podocyte proliferation (MCD, MGN), p21, p27, and p57 expression
      did not change. In contrast, there was a uniform decrease in p27 and p57
      immunostaining in diseases with podocyte proliferation (cellular FSGS, CG, and
      HIVAN). This was accompanied by the de novo expression of p21 in podocytes.
      CONCLUSIONS: Our results show that podocyte quiescence may require the presence
      of the CDK inhibitors p27 and p57. In human glomerular diseases, a decrease in
      p27 and p57 may be permissive for the altered proliferative podocyte phenotype.
      p21 may have a multifactorial role in podocyte cell cycle regulation.

PMID- 10916089
TI  - Tempol, a membrane-permeable radical scavenger, reduces oxidant stress-mediated
      renal dysfunction and injury in the rat.
AB  - BACKGROUND: The generation of reactive oxygen species (ROS) contributes to the
      pathogenesis of renal ischemia-reperfusion injury. The aim of this study was to
      investigate the effects of tempol in (1) an in vivo rat model of renal
      ischemia/reperfusion injury and on (2) cellular injury and death of rat renal
      proximal tubular (PT) cells exposed to oxidant stress in the form of hydrogen
      peroxide (H2O2). METHODS: Male Wistar rats underwent bilateral renal pedicle
      clamping for 45 minutes followed by reperfusion for six hours. Tempol (30
      mg/kg/h), desferrioxamine (DEF; 40 mg/kg/h), or a combination of tempol (30
      mg/kg/h) and DEF (40 mg/kg/h) were administered prior to and throughout
      reperfusion. Plasma concentrations of urea, creatinine, Na+, gamma-glutamyl
      transferase (gammaGT), aspartate aminotransferase (AST), and urinary Na+ and N
      acetyl-beta-D-glucosaminidase (NAG) were measured for the assessment of renal
      function and reperfusion injury. Kidney myeloperoxidase (MPO) activity and
      malondialdehyde (MDA) levels were measured for assessment of polymorphonuclear
      (PMN) cell infiltration and lipid peroxidation, respectively. Renal sections were
      used for histologic grading of renal injury and for immunohistochemical
      localization of nitrotyrosine and poly(ADP-ribose) synthetase (PARS). Primary
      cultures of rat PT cells were incubated with H2O2 (1 mmol/L for 4 h) either in
      the absence or presence of increasing concentrations of tempol (0.03 to 10
      mmol/L), DEF (0.03 to 10 mmol/L), or a combination of tempol (3 mmol/L) or DEF (3
      mmol/L). PT cell injury and death were determined by evaluating mitochondrial
      respiration and lactate dehydrogenase (LDH) release, respectively. RESULTS: In
      vivo, tempol significantly reduced the increase in urea, creatinine, gammaGT,
      AST, NAG, and FENa produced by renal ischemia/reperfusion, suggesting an
      improvement in both renal function and injury. Tempol also significantly reduced
      kidney MPO activity and MDA levels, indicating a reduction in PMN infiltration
      and lipid peroxidation, respectively. Tempol reduced the histologic evidence of
      renal damage associated with ischemia/reperfusion and caused a substantial
      reduction in the staining for nitrotyrosine and PARS, suggesting reduced
      nitrosative and oxidative stress. In vitro, tempol significantly attenuated H2O2
      mediated decrease in mitochondrial respiration and increase in LDH release from
      rat PT cells, indicating a reduction in cell injury and death. Both in vivo and
      in vitro, the beneficial actions of tempol were similar to those obtained using
      the Fe2+ chelator DEF. However, coadministration of DEF and tempol did not
      produce any additional beneficial actions against renal ischemia/reperfusion
      injury or against oxidative stress-mediated PT cell injury/death. CONCLUSION: Our
      results suggest that the membrane-permeable radical scavenger, tempol, reduces
      the renal dysfunction and injury associated with ischemia/reperfusion of the
      kidney.

PMID- 10916091
TI  - Possible relationship of monocyte chemoattractant protein-1 with diabetic
      nephropathy.
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a specific chemokine to
      recruit and activate monocytes from the circulation to inflammatory site. In
      diabetic nephropathy, similar to other glomerulonephropathies, infiltration and
      activation of monocytes/macrophages in glomerulus have been implicated in the
      development of glomerular injury. The aim of the present study was to examine a
      possible relationship of MCP-1 with diabetic nephropathy and to investigate the
      role of glycated albumin (Gly-Alb) as well as high concentration of glucose (HG)
      on MCP-1 production by cultured human mesangial cells. METHODS: MCP-1 in serum or
      urine and urinary albumin (Alb) as well as several clinical parameters such as
      plasma glucose, serum Gly-Alb, and hemoglobin A1c (HbA1c) were measured after
      overnight fasting in 16 control subjects and 54 diabetic patients. The
      relationships between the levels of urinary Alb and urinary or serum MCP-1 and
      also between the values of respective clinical parameter and urinary MCP-1 levels
      were analyzed. Next, using cultured human mesangial cells, we investigated the
      role of Gly-Alb and/or HG on the gene and protein expression of MCP-1. RESULTS:
      Urinary levels (ng/g creatinine), but not serum levels, of MCP-1 increased in
      accordance with the extent of albuminuria. In all subjects, there were
      significant correlations between the urinary levels of Alb and MCP-1 (r = 0.746,
      P < 0.0001) and between the levels of serum Gly-Alb and urinary MCP-1 (r = 0.475,
      P < 0.0001). In cultured human mesangial cells, the gene and protein expression
      of MCP-1 was dose and time dependently up-regulated by Gly-Alb. HG slightly but
      significantly stimulated MCP-1 expression. The combination of Gly-Alb and HG
      showed the greatest stimulation in more than an additive manner on MCP-1
      production. CONCLUSIONS: This study suggests that facilitated MCP-1 production by
      mesangial cells in diabetic milieu contributes to the initiation and progression
      of diabetic nephropathy.

PMID- 10916092
TI  - Osteopontin mediates hypoxia-induced proliferation of cultured mesangial cells:
      role of PKC and p38 MAPK.
AB  - BACKGROUND: We previously reported that hypoxia induces the proliferation of
      cultured mesangial cells mediated by the stimulation of intracellular calcium and
      the activation of protein kinase C (PKC). In the present study, we examined the
      roles of mesangial cell specific growth factors (platelet-derived growth factor
      and endothelin-1) and osteopontin (OPN) in hypoxia-induced proliferation of
      mesangial cells. In addition, we determined the effect of hypoxia on p38 mitogen
      activated protein (MAP) kinase activity and the roles of both PKC and p38 MAP
      kinase in hypoxia-induced alterations in OPN and mesangial cell growth. METHODS:
      Quiescent cultures of mesangial cells were exposed to hypoxia (3% O2) or normoxia
      (18% O2) in a serum-free medium, and [3H]-thymidine incorporation, OPN protein
      and mRNA expression, and p38 MAP kinase activity were assessed. RESULTS: Hypoxic
      conditioned medium mimicked the effect of hypoxia on thymidine incorporation,
      suggesting the release of diffusable growth promoting factor(s) by hypoxia.
      Neither anti-endothelin-1 nor anti-platelet-derived growth factor-neutralizing
      antibodies had an effect on increased thymidine incorporation induced by hypoxia.
      However, blocking the effects of OPN either with anti-OPN antibody or its beta3
      integrin receptor antibody completely prevented the hypoxia-induced increase in
      thymidine incorporation. Hypoxia also stimulated OPN protein and mRNA levels.
      Hypoxia caused an acute activation of p38 MAP kinase, which was inhibited by both
      verapamil and an inhibitor of PKC (calph C). PKC inhibitor and an inhibitor of
      p38 MAP kinase (SB203580) reduced the hypoxia-induced stimulation of both OPN and
      cell growth. CONCLUSIONS: These studies provide, to our knowledge, the first
      evidence demonstrating the role of OPN in hypoxia-induced proliferation of
      mesangial cells. In addition, hypoxia causes an activation of p38 MAP kinase in a
      calcium- and PKC-dependent manner, and the activation of PKC and p38 MAP kinase
      appears to be involved in the stimulation of both OPN and mesangial cell
      proliferation induced by hypoxia.

PMID- 10916093
TI  - Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced
      polyuria.
AB  - BACKGROUND: Cisplatin (CP)-induced polyuria in rats is attributed to decreased
      medullary hypertonicity and/or an end-organ resistance to vasopressin. However,
      the roles of renal aquaporins (AQPs) have not yet been explored. METHODS: Male
      Sprague-Dawley rats (230 to 245 g) received either a single injection of CP (5
      mg/kg, N = 4) or saline (N = 4) intraperitoneally five days before sacrifice.
      Urine, blood, and kidney samples were analyzed. RESULTS: Platinum accumulated in
      the cortex and outer medulla of CP-treated rats (39.05 +/- 7.50 and 36.48 +/-
      12.44 microg/g vs. 2.52 +/- 0.43 and 1.87 +/- 0.84 microg/g dry tissue in
      controls, respectively). Histologically, tubular damage and decreased AQP1
      immunolabeling were detected in the S3 segment of proximal tubules. CP treatment
      caused 4.4- and 4.8-fold increases, respectively, in blood urea nitrogen and
      urine volume, and a 4. 4-fold decrease in urine osmolality. Immunoblots showed
      that AQP2 and AQP3 were significantly reduced to 33 +/- 10% (P < 0.001) and 69 +/
      11% (P < 0.05), respectively, in the inner medulla of CP-treated rats.
      Immunocytochemical analysis showed a decrease in AQP2 labeling in the inner
      medulla of CP-treated rats. Northern hybridization revealed a 33 +/- 11% (P <
      0.002) decrease in AQP2 mRNA expression in the inner medulla of CP-treated rats.
      AQP1 protein expression levels were modestly (67 +/- 7%, P = 0.057) and
      significantly (53 +/- 13%, P < 0.007) decreased in outer and inner medullae,
      respectively, of CP-treated rats. CONCLUSIONS: CP-induced polyuria in rats is
      associated with a significant decrease in the expression of collecting duct (AQP2
      and AQP3) and proximal nephron and microvascular (AQP1) water channels in the
      inner medulla.

PMID- 10916094
TI  - Diminished natriuretic response to dopamine in old rats is due to an impaired D1
      like receptor-signaling pathway.
AB  - BACKGROUND: Dopamine (DA) causes natriuresis and diuresis, which results from
      activation of D1-like receptor (D1R) located on proximal tubules. Earlier, we
      reported that DA failed to inhibit Na,K-ATPase in proximal tubules of old Fischer
      344 rats. The present study was designed to investigate the functional
      consequence of this phenomenon. METHODS: Measurements of the functional
      (natriuretic and diuretic) response to intravenously infused DA and SKF 38393
      (D1R agonist) in adult (6 month) and old (24 month) Fischer 344 rats were taken.
      Biochemical measurements were carried out to determine the potential defects in
      D1R and its signaling pathway in proximal tubules of old rats. RESULTS: We found
      that intravenous infusion of DA and SKF 38393 caused natriuresis and diuresis in
      adult rats, but this response was blunted in old rats. In the isolated proximal
      tubules, DA and SKF 38393 inhibited Na,H-exchanger (NHE) in adult rats; however,
      this inhibition was attenuated in old rats. Radioligand binding revealed
      approximately 46% reduction in D1R binding sites in brush border membranes (BBMs)
      in old compared with adult rats. SKF 38393 stimulated [35S]GTPgammaS binding in
      BBM in adult rats, but not in old rats, suggesting an impaired D1R-G protein
      coupling. DA and SKF 38393 stimulated adenylyl cyclase (AC) activity in adult but
      not in the old rats. Forskolin and NaF stimulated AC activity in a comparable
      manner in adult and old rats, indicating no defect in AC and G proteins. DA and
      SKF 38393 failed to stimulate protein kinase A (PKA) activity in proximal tubules
      of old rats. Dibutyryl-cAMP-mediated PKA activation was also absent in old rats.
      CONCLUSIONS: A decrease in D1R binding sites, a coupling defect with G proteins,
      and a defect in PKA activation lead to diminished DA-mediated inhibition of NHE
      in old rats, which may contribute to the blunted natriuretic response to DA in
      these animals.

PMID- 10916095
TI  - Distribution of renal medullary hyaluronan in lean and obese rabbits.
AB  - BACKGROUND: Obese individuals have an expanded interstitium in the renal inner
      medulla (IM), which stains positively with periodic acid-Schiff and Alcian blue.
      In obese dogs, the IM is also expanded, with hyaluronan (HA) content being 2.4
      times control. METHODS: We determined the anatomic pattern of renal HA deposition
      following weight gain, using an animal model of obesity consisting of young
      rabbits (N = 10), representing animals entering into the study, lean rabbits (N =
      19), fed a control diet, and obese rabbits (N = 19), fed a high-fat diet (15%
      fat, by fortifying with corn oil and lard, in a ratio of 2:1) for two to three
      months. Tissue was papain digested, and HA was recovered in a phosphate or a Tris
      buffer and detected by an indirect immunoabsorbent competition assay. RESULTS:
      Rabbits fed a high-fat diet for 8 to 12 weeks gained weight (37%) and became
      mildly hypertensive (10 mm Hg). In lean rabbits, HA was low in the renal cortex
      (6 +/- 30 microg/g tissue), increased steadily across the outer medulla (OM; 79
      +/- 28 microg/g tissue) and was uniformly high in the IM (192 +/- 28 microg/g
      tissue) when recovered in a Tris buffer; these levels of tissue HA did not change
      during the three-month period of dietary intervention. In obese rabbits, the
      renal medullary interstitium was expanded and stained intensely with periodic
      acid Schiff and Alcian blue, and tissue HA was elevated in the IM (448 +/- 25
      microg/g tissue) but not the cortex (5 +/- 25 microg/g tissue) or the OM (85 +/-
      25 microg/g tissue). The significant difference was due to those IM samples taken
      from the renal papilla; IM samples from the body of the kidney did not
      significantly differ among the lean, obese, and young rabbits. CONCLUSION: The
      elevated renal HA associated with weight gain is limited to the IM and occurs
      most consistently in the papilla, which is the region of the kidney that is most
      vulnerable to distention caused by elevated renal interstitial hydrostatic
      pressure.

PMID- 10916096
TI  - Human tissue kallikrein gene delivery attenuates hypertension, renal injury, and
      cardiac remodeling in chronic renal failure.
AB  - BACKGROUND: Tissue kallikrein cleaves kininogen substrate to produce the potent
      vasodilating peptide kinin, which plays important roles in cardiovascular and
      renal function. To explore cardiac and renal potential protective effects of
      kallikrein gene delivery in chronic renal failure, we delivered adenovirus
      carrying the human tissue kallikrein cDNA (cHK) into rats with 5/6 reduction of
      renal mass. METHODS: Expression of human tissue kallikrein in rats was assessed
      by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase
      chain reaction (RT-PCR)/Southern blotting. Physiological parameters monitored in
      rats included systolic blood pressure, heart rate, and urinary excretion of
      protein, albumin, kinin, cGMP, cAMP, and nitrate/nitrites. Systemic and regional
      hemodynamics were measured by fluorescent-labeled microspheres. Heart weight and
      myocyte diameter were used to assess left ventricular hypertrophy. Quantitative
      and qualitative morphological analyses were used to evaluate histologic changes
      in kidney and heart sections. RESULTS: Active tissue kallikrein reached a peak
      serum level of 463 +/- 76 ng/mL following gene delivery and returned to control
      levels within 21 days. A maximal blood pressure reduction of 37 mm Hg was
      observed within one week in rats receiving kallikrein gene delivery as compared
      with control rats receiving adenovirus containing the luciferase gene (159 +/- 5
      vs. 196 +/- 6 mm Hg, N = 15, P < 0.001), and a significant blood pressure
      difference continued for five weeks postgene delivery. Kallikrein gene delivery
      significantly decreased total urinary protein and albumin excretion and increased
      levels of urinary kinin, nitrite/nitrate, and cGMP levels. Cardiac output and
      regional blood flow were also increased, while peripheral vascular resistance
      decreased. Kallikrein gene transfer reduced glomerular sclerotic lesions, tubular
      damage, lumenal protein cast accumulation, and interstitial inflammation in the
      kidney. Myocardial hypertrophy and fibrosis were also attenuated in rats
      receiving kallikrein gene delivery. CONCLUSIONS: These findings indicated that
      kallikrein gene delivery attenuates hypertension and protects against renal
      injury and cardiac remodeling in the rat remnant kidney model of chronic renal
      failure.

PMID- 10916097
TI  - Renal nitric oxide production during the early phase of experimental diabetes
      mellitus.
AB  - BACKGROUND: Diabetic nephropathy (DN) is characterized by hyperfiltration and
      hypertrophy in experimental models of diabetes mellitus (DM). Several studies
      have demonstrated that the pathophysiologic and morphologic changes in DN are
      mediated by either an increase or decrease in renal nitric oxide (NO) production
      and/or activity. The goal of the present study was to determine the effects that
      the early diabetic state has on NO production in the kidney of rats with
      streptozotocin-induced DM. METHODS: Experimental DM was induced in rats with
      streptozotocin. Urinary NO production was measured, and levels and activity of
      the different NOS isoforms were determined by a combination of techniques,
      including immunoblotting, immunohistochemistry, diaphorase staining, and reverse
      transcription-polymerase chain reaction. RESULTS: During the first week of DM,
      urinary NO metabolites (uNO2 + NO3) were reduced as compared with controls, which
      were unrelated to changes in serum levels of NO. Total NO synthase (NOS) activity
      was reduced in the renal cortex beginning at 30 hours after the induction of DM.
      NADPH diaphorase staining of renal cortical slices showed reduced NOS activity in
      the macula densa in diabetic animals. By immunohistochemical staining with
      antibodies to the different isoforms of NOS, it was found that protein levels of
      the neuroneal NOS (nNOS) isoform was diminished in the macula densa. No changes
      were found in the levels of endothelial NOS (eNOS) activity and protein in the
      renal cortex in the early diabetic state. CONCLUSIONS: This study provides strong
      evidence that renal production of NO is reduced in early DM and that this
      reduction is associated with decreased levels of nNOS activity and protein in the
      macula densa.

PMID- 10916098
TI  - Comparative effects of potassium chloride and bicarbonate on thiazide-induced
      reduction in urinary calcium excretion.
AB  - BACKGROUND: The chronic low-grade metabolic acidosis that occurs in various renal
      disorders and in normal people, and that is related both to dietary net acid load
      and age-related renal functional decline, may contribute to osteoporosis by
      increasing urine calcium excretion. Administration of potassium (K) alkali salts
      neutralizes acid and lowers urine calcium excretion. Urine calcium excretion also
      can be reduced by the administration of thiazide diuretics, which are often given
      with supplemental K to avoid hypokalemia. We determined whether the K alkali salt
      potassium bicarbonate (KHCO3) and the thiazide diuretic hydrochlorothiazide
      (HCTZ) combined is more effective in reducing urinary calcium than KHCO3 alone or
      HCTZ combined with the conventionally coadministered nonalkalinizing K salt
      potassium chloride (KCl). METHODS: Thirty-one healthy men and women aged 50 or
      greater were recruited for a four-week, double-blind, randomized study. After a
      baseline period of 10 days with three 24-hour urine and arterialized blood
      collections, subjects were randomized to receive either HCTZ (50 mg) plus
      potassium (60 mmol daily) as either the chloride or bicarbonate salt. Another 19
      women received potassium bicarbonate (60 mmol) alone. After two weeks, triplicate
      collections of 24-hour urines and arterialized bloods were repeated. RESULTS:
      Urinary calcium excretion decreased significantly in all groups. KHCO3 alone and
      HCTZ + KCl induced similar decreases (-0.70 +/- 0.60 vs. -0.80 +/- 1. 0 mmol/day,
      respectively). Compared with those treatments, the combination of HCTZ + KHCO3
      induced more than a twofold greater decrease in urinary calcium excretion (-1.8
      +/- 1.2 mmol/day, P < 0. 05). Both HCTZ + KHCO3 and KHCO3 alone reduced net acid
      excretion significantly (P < 0.05) to values of less than zero. CONCLUSIONS:
      KHCO3 was superior to KCl as an adjunct to HCTZ, inducing a twofold greater
      reduction in urine calcium excretion, and completely neutralizing endogenous acid
      production so as to correct the pre-existing mild metabolic acidosis that an acid
      producing diet usually induces in older people. Accordingly, for reducing urine
      calcium excretion in stone disease and osteoporosis, the combination of HCTZ +
      KHCO3 may be preferable to that of HCTZ + KCl.

PMID- 10916099
TI  - A novel mechanism for skeletal resistance in uremia.
AB  - BACKGROUND: In treating secondary hyperparathyroidism, the target level of serum
      intact parathyroid hormone (I-PTH) should be three to five times normal to
      prevent adynamic bone disease. In circulation, there is a non-(1-84) PTH
      truncated fragment, likely 7-84, which, in addition to PTH 1-84, is measured by
      most I-PTH immunoradiometric (IRMA) assays, giving erroneously high I-PTH values.
      We have developed a new IRMA assay in which the labeled antibody recognizes only
      the first six amino acids of the PTH molecule. Thus, this new IRMA assay (Whole
      PTH) measures only the biologically active 1-84 PTH molecule. METHODS: Using this
      new IRMA assay (Whole PTH) and the Nichols "intact" PTH assay, we compared the
      ability of each assay to recognize human PTH (hPTH) 1-84 and hPTH 7-84 and
      examined the percentage of non-1-84 PTH in circulation and in parathyroid glands.
      Possible antagonistic effects of the 7-84 PTH fragment on the biological activity
      of 1-84 PTH in rats were also tested. RESULTS: In 28 uremic patients, PTH values
      measured with the Nichols assay, representing a combined measurement of both hPTH
      1-84 and hPTH 7-84, were 34% higher than with the Whole assay (hPTH 1-84 only);
      the median PTH was 523 versus 318 pg/mL (P < 0.001). Similar results were found
      in 14 renal transplant patients. In osteoblast-like cells, ROS 17.2, 1-84 PTH (10
      8 mol/L) increased cAMP from 18.1 +/- 1.25 to 738 +/- 4.13 mmol/well. Conversely,
      the same concentration of 7-84 PTH had no effect. In parathyroidectomized rats
      fed a calcium-deficient diet, 7-84 PTH was not only biologically inactive, but
      had antagonistic effects on 1-84 PTH in bone. Plasma calcium was increased (0.65
      mg/dL) two hours after 1-84 PTH treatment, while 7-84 PTH had no effect. When 1
      84 PTH and 7-84 PTH were given simultaneously in a 1:1 molar ratio, the calcemic
      response to 1-84 PTH was decreased by 94%. In normal rats, the administration of
      1-84 PTH increased renal fractional excretion of phosphate (11.9 to 27.7%, P <
      0.001). However, when 1-84 PTH and 7-84 PTH were given simultaneously, the 7-84
      PTH decreased the phosphaturic response by 50.2% (P < 0.005). Finally, in
      surgically excised parathyroid glands from six uremic patients, we found that
      44.1% of the total intracellular PTH was the non-PTH (1-84), most likely PTH 7
      84. CONCLUSION: In patients with chronic renal failure, the presence of high
      circulating levels of non-1-84 PTH fragments (most likely 7-84 PTH) detected by
      the "intact" assay and the antagonistic effects of 7-84 PTH on the biological
      activity of 1-84 PTH explain the need of higher levels of "intact" PTH to prevent
      adynamic bone disease.

PMID- 10916100
TI  - Long-term comparison of losartan and enalapril on kidney function in hypertensive
      type 2 diabetics with early nephropathy.
AB  - BACKGROUND: The objectives of this study were to compare the effects of the
      angiotensin II receptor blocker, losartan, to those of the angiotensin-converting
      enzyme inhibitor, enalapril, on albuminuria and renal function in relationship to
      clinic and ambulatory blood pressure (ABP) in hypertensive type 2 diabetic
      subjects with early nephropathy. The tolerability of these agents and their
      effect on the metabolic profile were also evaluated. METHODS: The study was a one
      year prospective, double-blind trial with losartan and enalapril administered
      alone or in combination with hydrochlorothiazide and other antihypertensive
      agents. ABP and renal and biochemical parameters were measured at baseline and
      after 12, 28, and 52 weeks of active treatment. Ninety-two hypertensive type 2
      diabetics with early nephropathy completed the study. RESULTS: Both losartan and
      enalapril administered alone or in combination with other agents induced
      significant reductions in sitting clinic (P < 0.05) and ABP (P < 0.002) without a
      statistical difference between groups. Geometric means for urinary albumin
      excretion (UAE) decreased significantly (P < 0.001) in patients treated with
      losartan from 64. 1 to 41.5 microg/min and in those treated with enalapril from
      73.9 to 33.5 microg/min after 52 weeks of therapy. A significant relationship (P
      < 0.05) between changes in systolic and diastolic ABP and the decrease in UAE at
      52 weeks was seen in both groups. The decline in glomerular filtration rate (GFR)
      was stabilized at the end of therapy and was identical in both treatment groups.
      Treatment with enalapril was associated with a significantly higher incidence of
      cough (P = 0.006) and a rise in serum uric acid (P = 0.002) compared with
      losartan. CONCLUSIONS: Our results indicate that a one-year course of
      antihypertensive therapy with either losartan or enalapril significantly reduces
      UAE in hypertensive type 2 diabetic patients with early nephropathy. The
      reduction in UAE with each treatment is similarly related to decrements in ABP.
      In addition, the rate of decline in GFR is similar in both treatment groups.

PMID- 10916101
TI  - Relationship between weight at birth and the number and size of renal glomeruli
      in humans: a histomorphometric study.
AB  - BACKGROUND: The number of nephrons in humans varies considerably under normal
      circumstances, and retarded intrauterine growth has been reported to be
      associated with a significant reduction in nephron number. Low nephron number may
      be an independent risk factor for the development of hypertension. We therefore
      decided to evaluate the relationship between body weight at birth and the number
      and size of nephron units. METHODS: We examined coronal sections of the kidneys
      of 35 neonates who died within two weeks of birth because of hyaline membrane,
      infectious complications, brain hemorrhage, or perinatal hypoxia and had no
      urinary congenital malformations. Nine of them (5 males and 4 females) were
      between 36 and 37 weeks of gestation, and the rest had 38 or more weeks of
      gestation. Eighteen neonates weighed less than 2500 g at birth [low birth weight
      (LBW); 9 females and 9 males], and 17 had weights above this value [normal birth
      weight (NBW); 8 females and 9 males]. In each section, glomeruli present in four
      sequential subcapsular microscopic fields, corresponding to 0.6 mm2, were
      counted; in addition, the area of each of 65 consecutive glomeruli was determined
      by a computerized measurement system. Glomerular volume was calculated from the
      glomerular area. Linear regression analysis was used to test the relationship
      between glomerular number and size and the weight at birth. RESULTS: The number
      of glomeruli per 0.6 mm2 of renal cortex was 92.9 +/- 4.85 in the LBW and 105.8
      +/- 3.91 in NBW (P < 0.0001). Glomerular volume (micro(3) x 10(-3)) was 529.1 +/-
      187.63 in the LBW group and 158.0 +/- 49.89 in the NBW group (P < 0.0001). The
      glomeruli occupied 8.59 +/- 1.38% of the kidney area under examination in the LBW
      group and 14.3 +/- 2.75% in the NBW group (P < 0.0001). There were significant
      direct correlations between the weight at birth and the number of glomeruli (r =
      0.870, P < 0.0001) and area occupied by glomeruli (r = 0.935, P < 0.0001). There
      were inverse correlations between the number of glomeruli and the volume of the
      glomeruli (r = -0.816, P < 0.0001) and the weight at birth and glomerular volume
      (r = -0.848, P < 0.0001). These findings were independent of sex and race (black
      vs. white). Essential arterial hypertension existed in 38.9% of the mothers of
      children with LBW and in 5.9% of the mothers of children with NBW (P < 0.05).
      Smoking habits existed in 50% of the mothers of LBW children and in 11.8% of the
      mothers of NBW children (P < 0.05). CONCLUSION: There are strong correlations
      between glomerular number (direct) and size (inverse) with LBW in this cohort.
      Endowment with decreased nephron numbers may be a risk factor for hypertension
      and the rate of progression of renal disease.

PMID- 10916102
TI  - Evaluation of duplex ultrasound and captopril renography for detection of
      renovascular hypertension.
AB  - BACKGROUND: Renovascular hypertension is the most common form of curable
      secondary hypertension and, if untreated, may lead to end-stage kidney disease.
      Given that renal function and hypertension may improve after renal angioplasty,
      it is pertinent to identify patients with renal artery stenosis. The aim of the
      present study was to evaluate both duplex ultrasound and captopril renography for
      detection of renal artery stenosis among hypertensive patients. METHODS: To avoid
      selection bias, all patients referred to our center for evaluation of
      renovascular hypertension were asked to participate in the study. Patients were
      examined by intra-renal duplex ultrasound (N = 121), measuring pulsatility index
      and acceleration of the blood flow during early systole. In 98 patients, 99mTc
      DTPA captopril renography was performed in conjunction with duplex ultrasound.
      Renal angiography was performed in all patients regardless of the results of the
      noninvasive tests. RESULTS: The prevalence of renal artery stenosis was 19%. In
      the 98 patients examined by both duplex ultrasound and captopril renography,
      sensitivity and positive predictive values for detection of a renal artery
      stenosis of 50% degree or more were 84 and 76%, respectively, for duplex
      ultrasound, whereas captopril renography was associated with a sensitivity and
      positive predictive value of 68% for both (P = NS). Specificity and negative
      predictive values were 94 and 96%, respectively, for duplex ultrasound, whereas
      the corresponding values for captopril renography were 92% for both (P = NS).
      Specificity and negative predictive values were 94 and 96%, respectively, for
      duplex ultrasound, whereas the corresponding values for captopril renography were
      92% for both (P = NS). CONCLUSIONS: Both duplex ultrasound and captopril
      renography are associated with high specificity and negative predictive values
      for detection of renal artery stenosis. Sensitivity and positive predictive
      values are at least as good for duplex ultrasound compared with captopril
      renography. Given that duplex ultrasound is easier to perform and more cost
      effective, we propose that it should be the method of first choice when screening
      for renal artery stenosis in a hypertensive population.

PMID- 10916103
TI  - Impact of interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene
      polymorphism on IgA nephropathy.
AB  - BACKGROUND: It is evident that cytokines play an important role in the
      pathogenesis as well as disease progression in IgA nephropathy (IgAN). The level
      of cytokine production is influenced by different genotypes that reflect gene
      polymorphism of the pertinent cytokine. Interleukin-1 receptor antagonist (IL
      1ra) and tumor necrosis factor-alpha (TNF-alpha) gene polymorphism have been
      found to affect disease susceptibility and activity in several inflammatory
      diseases. However, the impact of these polymorphisms in IgAN patients has not
      previously been thoroughly studied. METHODS: We investigated 111 cases of biopsy
      proven IgAN and 100 healthy, normal controls for their IL-1ra and TNF-alpha gene
      polymorphism. IL-1ra gene polymorphism was characterized as a variable number of
      tandem repeats of a 86 bp sequence within intron 2. Five alleles were identified
      and were designated as IL1RN*1, IL1RN*2, IL1RN*3, IL1RN*4, and IL1RN*5,
      corresponding to 4, 2, 5, 3, 6 repeats, respectively. A polymorphism in the
      promoter region of the TNF-alpha gene was also studied. This polymorphism
      involved a guanidine to adenosine transition at position -308 and was designated
      as TNF1 (-308G) and TNF2 (-308A). RESULTS: There were 54 male and 57 female
      patients with a mean age of 30.3 +/- 12.5 years and a disease duration of 66. 8
      +/- 47.2 months. The mean duration of the follow-up period was 47. 3 +/- 32.6
      months. In the patient group, the allele frequencies of IL1RN*1, IL1RN*2,
      IL1RN*3, IL1RN*4, and IL1RN*5 were 89.6%, 9.9%, 0%, 0.5%, and 0%, respectively,
      whereas the corresponding carriage rates were 100%, 19.8%, 0%, 0.9%, and 0%,
      respectively. An excessive carriage of IL2RN*2 was found in the patients when
      compared with normal controls (allele frequency, 9.9 vs. 2.5%, P < 0.0001). The
      allele frequencies of TNF1 and TNF2 were 94.1 and 5.9%, respectively, and the
      carriage rates were 99.1 and 10.8%, respectively, in the patients, which was not
      significantly different from those of normal controls. When the patients were
      stratified into mild and severe groups according to their initial presentation,
      none of the studied alleles correlated with the severity. However, patients with
      gross hematuria were associated with a higher carriage rate of TNF2 when compared
      with patients without gross hematuria (allele frequency, 15. 4 vs. 4.6%, P =
      0.0552; carriage rate, 30.8% vs. 8.2%, P = 0.0272). Renal survival analysis
      revealed that the TNF2 carrier had a renal survival comparable with TNF2 (-)
      patients. However, the carriage of the IL1RN*2 allele was associated with a
      significantly poorer long-term outcome with a median survival time of 72 months,
      as compared with those without IL1RN*2 (134 months, P < 0.01). CONCLUSION: IL-1ra
      and TNF-alpha gene polymorphism may affect disease susceptibility as well as
      disease activity and long-term outcome in human IgAN. Treatment with an IL-1ra or
      IL-1 blocking agent may be relevant in those carrying the IL1RN*2 allele.

PMID- 10916104
TI  - Effect of vitamin E-bonded membrane on the 8-hydroxy 2'-deoxyguanosine level in
      leukocyte DNA of hemodialysis patients.
AB  - BACKGROUND: 8-Hydroxy 2'-deoxyguanosine (8-OHdG) of leukocyte DNA has been
      identified as a surrogate marker of oxidative stress in chronic hemodialysis (HD)
      patients. In this study, we focused on the determinants of the 8-OHdG level in
      leukocyte DNA of HD patients. We further investigated the influence of vitamin E
      modified, regenerated cellulose (CL-E) membrane on the oxidative DNA damage,
      intracellular reactive oxygen species (ROS) production of granulocytes, and
      plasma alpha-tocopherol concentration. METHODS: 8-OHdG content in cellular DNA of
      leukocytes was measured by a high-performance liquid chromatography
      electrochemical detection (HPLC-ECD) method. Intracellular production of ROS,
      H2O2 and O2-. were analyzed by flow cytometry in leukocytes with and without
      phorbol-12-myristate-13-acetate (PMA) stimulation before dialysis, as well as at
      15 and 30 minutes of dialysis. Plasma alpha-tocopherol concentration was measured
      by a HPLC method, and the value of alpha-tocopherol was corrected by total blood
      lipid concentration. RESULTS: In the prospective cross sectional study, the mean
      8-OHdG level in leukocyte DNA was equally lower in the patients of the CL-E,
      polymethylmethacrylate (PMMA), and polysulfone (PS) groups as compared with the
      cellulosic group (ANOVA, P < 0.001). The leukocyte 8-OHdG level correlated
      negatively with plasma alpha-tocopherol and blood lipid-adjusted plasma alpha
      tocopherol, but correlated positively with serum iron and percentage of
      transferrin saturation. Forward stepwise multiple regression showed that dialysis
      membrane type, serum iron, and blood lipid-adjusted plasma alpha-tocopherol were
      the independent determinants of the leukocyte 8-OHdG level in HD patients. Like
      synthetic membranes, granulocyte ROS production was less augmented during
      dialysis with the CL-E membrane as compared with the cellulose membrane. Exposure
      to cellulose membrane impaired intracellular ROS production of granulocytes in
      response to PMA challenge, whereas the CL-E and synthetic membranes improved the
      granulocyte responsiveness to PMA. In the longitudinal cross-over study, the 8
      OHdG level significantly decreased, and blood lipid-adjusted plasma alpha
      tocopherol increased after switching the cellulose membrane to CL-E or synthetic
      membrane for eight weeks. In contrast, the 8-OHdG level dramatically rose, and
      blood lipid-adjusted plasma alpha-tocopherol declined after shift of CL-E or
      synthetic membrane to the cellulose membrane. CONCLUSIONS: CL-E membrane
      exhibited biocompatible and bioactive characteristics. Like synthetic membranes,
      treatment with a CL-E dialyzer effectively reduced the 8-OHdG content in
      leukocyte DNA, suppressed intracellular ROS production of granulocytes, and
      preserved the plasma level of vitamin E. It could further improve granulocyte
      responsiveness to a PMA challenge. Reduced DNA damage and improved immune
      function of leukocytes may reduce the cancer and infection risks in chronic HD
      patients.

PMID- 10916105
TI  - Impact of biofeedback-induced cardiovascular stability on hemodialysis tolerance
      and efficiency.
AB  - BACKGROUND: Hypotension is caused by a drop in blood volume during
      ultrafiltration, followed by vasoconstriction and reduced perfusion in some
      regions of the body. METHODS: We carried out a prospective controlled crossover
      study on 12 hypotension-prone patients with two different modalities: (A) acetate
      free hemodiafiltration with standard ultrafiltration control, and (B) acetate
      free hemodiafiltration with monitoring of blood volume and automatic biofeedback
      with machine-driven adjustments on ultrafiltration and dialysate conductivity. We
      measured urea Kt/V and equilibrated Kt/V (eKt/V), urea rebound, and urea removal.
      Hypotensive episodes and interventions were recorded. RESULTS: In group B, fewer
      hypotensive episodes were recorded (24 out of 72 in group B vs. 59 out of 72 in
      group A). Saline infusion was required in 57 cases in group A and 15 cases in
      group B. Urea Kt/V was 1.34 +/- 0.08 in group A and was 1.26 +/- 0.06 in group B;
      eKt/V was much higher in group B (1.12 +/- 0.05) than in group A (1.03 +/- 008).
      A significantly higher rebound was observed in group A (14.2 +/- 2.7%) compared
      with group B (6.4 +/- 2.3%). Discussion. A greater solute sequestration seems to
      occur during hemodialysis with hypotension. This results in lower eKt/V, enhanced
      postdialytic rebound, and lower solute removal. Higher efficiency can be observed
      when dialysis is carried out smoothly and cardiovascular stability is maintained.
      We conclude that new systems for blood volume monitoring and automatic
      biofeedback may not only reduce the number of hypotensive episodes during
      dialysis, but may also contribute to significantly increase the efficacy of the
      treatment.

PMID- 10916106
TI  - Effects of a reduced inner diameter of hollow fibers in hemodialyzers.
AB  - BACKGROUND: The clearance of middle molecules in high-flux hemodialyzers is due
      to the higher contribution of convection in the overall solute transport.
      Although net filtration can be maintained low by the machine control, internal
      filtration in the proximal part of the dialyzer remains high. The final fluid
      balance is achieved by significant amounts of backfiltration in the distal part
      of the dialyzer. To increase further middle molecule clearance (MMK),
      hemodiafiltration has been used. This technique, however, requires complex
      machines and large amounts of substitution fluid. We present a novel solution to
      increase the convective transport of middle molecules in high flux dialyzers
      without the need for substitution fluids. In particular, high-flux dialyzers with
      a reduced hollow fiber diameter are compared with standard dialyzers in terms of
      internal filtration and solute clearances. METHODS: Hemodialyzers with 175 micro
      inner diameter polysulfone fibers were compared with standard 200 micro
      polysulfone hollow fiber dialyzers. The study was carried out in vitro using a
      previously published method to measure internal filtration and backfiltration
      rates. The method is based on the detection by a gamma camera of segmental
      variations in concentration along the length of the dialyzer of a nondiffusable
      Tc99-labeled marker molecule injected in the blood in vitro circuit. At the same
      time, pressures were detected in the blood and dialysate compartment. The system
      was operated at zero net filtration maintaining volumetrically constant both
      dialysate and blood circuits. In vivo clearances were also measured for solutes
      with different molecular weight. RESULTS: The pressure drop in the blood
      compartment at 300 mL/min of blood flow passed from 112 to 159 mm Hg. At the same
      blood flow, the internal filtration-backfiltration rates increased from 23. 1 to
      48.2 mL/min. This resulted in a significant increase of in vivo in clearances of
      vitamin B12 and inulin of more than 30%. Urea, creatinine, and phosphate
      clearance did not display any change. CONCLUSIONS: A reduction of the inner
      diameter of the hollow fibers in high-flux dialyzers may result in a significant
      increase of the blood compartment resistance. In turn, this results in increased
      rates of internal filtration and backfiltration. The practical effect in clinical
      dialysis is demonstrated on middle molecules. While, in fact, the clearances for
      small solutes such as urea and creatinine are not affected, the clearances of
      larger solutes such as vitamin B12 or inulin increase significantly (P < 0.01).

PMID- 10916107
TI  - Potential of dual-skinned, high-flux membranes to reduce backtransport in
      hemodialysis.
AB  - BACKGROUND: Potential backfiltration of cytokine-inducing material is a clinical
      concern during hemodialysis conducted with high-flux membranes. Novel hollow
      fiber membranes were developed that had asymmetric convective solute transport
      properties, aimed at reducing the passage of potentially harmful molecules from
      dialysate to blood, while maintaining the desired fluid and solute movement from
      blood to dialysate. METHODS: Sieving coefficient as a function of molecular
      weight was measured in vitro using polydisperse dextrans. Measurements were
      conducted using two different flat-sheet membranes in series or using hollow
      fiber membranes having two integrally formed skin layers. Based on measured
      experimental parameters, model calculations simulated the performance of a
      clinical-scale dialyzer containing these new membranes versus that of a
      commercially available high-flux dialyzer. RESULTS: Asymmetric convective solute
      transport was demonstrated using both commercial flat-sheet and newly developed
      hollow-fiber membranes. For two flat-sheet membranes in series, the extent of
      asymmetric transport was dependent on the order in which the solution was
      filtered through the membranes. For the hollow-fiber membranes, the nominal
      molecular weight cut-off was 20 kD in the blood-to-dialysate direction and 13 kD
      in the dialysate-to-blood direction. For this membrane, model calculations
      predict that clearance of a beta2-microglobulin-sized molecule (11,800 D) would
      be significantly greater from blood to dialysate than in the reverse direction,
      even under conditions of zero net ultrafiltration. CONCLUSION: A novel hollow
      fiber dialysis membrane was developed that allows greater convective solute
      transport from blood to dialysate than from dialysate to blood.

PMID- 10916108
TI  - Temporal changes of cytokines and nitric oxide products in urine from renal
      transplant patients.
AB  - BACKGROUND: Acute rejection and urinary tract infection (UTI) both increase
      nitric oxide synthase (NOS) activity in urine from renal transplant patients.
      Also, with rejection, a regulatory interplay between nitric oxide (NO) and
      cytokines has been suggested. Thus, measurement of the temporal changes of NOS
      products and cytokines in urine will provide a strategy for the diagnosis of
      acute rejection and for its differentiation from UTI. METHODS: Soluble
      interleukins (ILs) and NOS-related products, cyclic GMP (cGMP), nitrate, and
      nitrite were measured in 192 urine samples consecutively collected from 13
      patients within the first three months of transplantation. Sixty-seven additional
      urine specimens were collected randomly from 24 patients for follow-up analysis
      of the nitrate test. RESULTS: Among patients who experienced rejection, the
      percentage (%) binding of IL-2 increased within the first five days (P = 0.0004)
      after transplantation and one to five days prior to the clinical diagnosis (dx)
      of rejection (P = 0.02). Tumor necrosis factor-alpha, IL-6, and IL-8 increased at
      the time of rejection dx (P < or = 0.01). With UTI, IL-2 (P = 0.01) decreased one
      to five days prior to dx, and IL-10 (P = 0.003) increased one to five days after
      dx. Although cGMP and nitrate are dependent variables, cGMP increased (P < or
      =0.0009) with both rejection and UTI, and nitrate increased (P = 0.0001) with
      rejection and decreased (P = 0.0001) with UTI. Prior to formal dx (1 to 5 days),
      urine nitrate clearly differentiated rejection (3004 to 7451 micromol/L) from UTI
      (90 to 885 micromol/L) and controls (1059 to 3235 micromol/L). The additional 67
      urines demonstrated that the sensitivity of the nitrate test for rejection and
      UTI was 100%. CONCLUSIONS: In renal transplant patients, specific temporal
      changes in urine cytokine levels do occur with acute rejection and UTI, but urine
      nitrate levels are the most precise at differentiating rejection from UTI.

PMID- 10916109
TI  - Influence of cold-storage conditions on renal function of autotransplanted large
      pig kidneys.
AB  - BACKGROUND: The consequences of ischemia/reperfusion injury (IRI) on delayed
      graft function (DGF) and graft survival for kidney recipients remain a matter of
      debate. Several strategies have been proposed to reduce IRI. We have shown that
      adding the anti-ischemic drug trimetazidine (TMZ) to different preservation
      solutions had beneficial effects on the function of reperfused rat and pig
      kidneys. METHODS: We analyzed the renal parameters of reperfused,
      autotransplanted large pigs following transplantation. The left kidneys were
      first removed and cold flushed with Euro-Collins (EC) and University of Wisconsin
      (UW) solutions (with or without 10-6 mol/L TMZ) and were stored for 48 hours at 4
      degrees C. The kidney was then autotransplanted, and the contralateral kidneys
      were removed. Creatinine clearance, natriuresis, proteinuria, the degree of
      interstitial fibrosis, the number of CD4, CD8, and macrophage-positive cells, and
      the amount of vascular cell adhesion molecule-1 were analyzed on kidney biopsies
      taken at 2, 4 to 5, and 10 to 12 weeks after surgery. RESULTS: The functions of
      the transplanted kidneys were better preserved after cold flushing with TMZ
      supplemented solutions than with TMZ-free solutions. Creatinine clearance was
      higher, and proteinuria was lower in animals transplanted with kidneys cold
      flushed with TMZ-supplemented solutions than with TMZ-free solutions. The
      cytoprotective action of TMZ also reduced interstitial fibrosis and the numbers
      of infiltrating CD4- and CD8-positive cells. CONCLUSION: These results indicate
      that the condition of cold preservation may influence long-term kidney graft
      functions and suggest that, to a certain extent, TMZ reduces the degree of
      interstitial fibrosis.

PMID- 10916110
TI  - Hyperhomocysteinemia in hemodialysis patients: effects of 12-month
      supplementation with hydrosoluble vitamins.
AB  - BACKGROUND: High-efficiency hemodialysis may induce a deficiency in hydrosoluble
      vitamins. Supplementation with B-complex vitamins has been shown to lower serum
      homocysteine concentrations in several groups, but relatively few studies have
      concerned hemodialysis patients. Our objectives were to determine the status in B
      complex vitamins in a large cohort of unsupplemented hemodialysis patients and to
      assess the effects of supplementation with hydrosoluble vitamins on serum
      homocysteine over one year. METHODS: Serum total homocysteine (tHcy), vitamin
      B12, folate, pyridoxal-5'-phosphate (P-5'-P; the active moiety of vitamin B6), as
      well as red blood cell folate concentrations, were measured in 168 chronic
      dialysis patients on three times weekly high-efficiency hemodialysis and not
      supplemented with hydrosoluble vitamins. Their methylenetetrahydrofolate
      reductase C677T (MTHFR) genotypes were also determined (homozygotes TT,
      heterozygotes CT, without mutation CC). All involved patients were then
      supplemented with hydrosoluble vitamins (once daily by mouth, DiaVite; R&D
      Laboratories, Minneapolis, MN, USA), and half of them were randomized to receive
      in addition 10 mg intravenously of folic acid posthemodialysis (30 mg
      intravenously per week). Serum tHcy was monitored after 6 and 12 months of
      supplementation in the 140 and 128 patients available for follow-up. RESULTS: At
      baseline, serum and red blood cell folate concentrations were within normal
      limits in all patients except for two with borderline serum folate (mean values
      of 21 +/- 8 and 1195 +/- 454 nmol/L), whereas serum vitamin B12 and P-5'-P were
      below normal in 11 and 65 patients, respectively (mean values of 327 +/- 215
      pmol/L and 19 +/- 16 nmol/L for the 168 patients). Initial tHcy levels were
      increased in all patients (mean 33.3 +/- 16.6 for a normal below 11.8 +/- 1.5
      micromol/L); tHcy significantly decreased to 23.5 +/- 7.6 micromol/L after six
      months (P < 0.0001 vs. baseline) and to 21.7 +/- 6.1 micromol/L after 12 months
      (P < 0.0001 vs. baseline) for the entire group, but was normalized in only four
      patients at 12 months. After six months, the mean reduction in tHcy was slightly
      but significantly greater for patients receiving intravenous folic acid (12.2 +/-
      18.5 micromol/L) compared with patients not receiving it (8.3 +/- 9.8 micromol/L,
      P < 0.05). However, at 12 months, no difference between both subgroups persisted.
      When considering the different genotypes, tHcy at baseline tended to be higher
      for TT than CT and CC (39.8 +/- 30.9 vs. 31.4 +/- 10.5 vs. 31.6 +/- 11.8
      micromol/L) and decreased to respective values of 21.1 +/- 6.9 versus 21.4 +/-
      6.1 versus 22.2 +/- 5.9 micromol/L at 12 months. The impact of the addition of
      folic acid to DiaVite appeared particularly significant in TT patients at six
      months. CONCLUSIONS: (1) Hyperhomocysteinemia was present in 100% of our
      hemodialysis patients. (2) Nearly 40% of our unsupplemented hemodialysis patients
      were deficient in vitamin B6. (3) Supplementation with DiaVite(R) has resulted in
      significant tHcy reductions for all three genotypes. (4) The impact of the
      proposed supplementation protocol was found after six months and was maintained,
      but did not increase further after 12 months of the same regimen. (5) The
      addition of intravenous folic acid has been associated with a more pronounced
      decrease in tHcy in TT patients.

PMID- 10916111
TI  - Delayed graft function influences renal function, but not survival.
AB  - BACKGROUND: In renal transplantation, the impact of delayed graft function (DGF)
      on prognosis is controversial. We analyzed the risk factors of DGF and its impact
      on graft function and prognosis. METHODS: Seven hundred thirty-four cadaveric
      renal transplants performed between 1983 and 1997 were analyzed. DGF was
      diagnosed when serum creatinine levels increased, remained unchanged, or
      decreased less than 10% per day in three consecutive days in the first week after
      transplantation. Creatinine clearances of more or less than 50 or 30 mL/min at
      one year were used as cut-off points for optimal and suboptimal graft function,
      respectively. The logistic regression model was used to identify independent risk
      factor related to DGF and renal function one year after transplantation. The Cox
      regression model was used to examine the influence of DGF on long-term graft
      survival. RESULTS: Multivariate analysis revealed the following risk factors for
      DGF: recipient pretransplantation mean arterial blood pressure of less than 100
      mm Hg (OR = 2.08, 95% CI, 1.43 to 3.03), female donor to male recipient
      combination (OR = 1.55, 95% CI, 1.02 to 2.35), donor age of more than 50 years
      (OR = 2.21, 95% CI, 1.49 to 3.26), cold ischemia time of more than 28 hours (OR =
      1.78, 95% CI, 1.19 to 2.63), and peak panel reactive antibodies of more than 50%
      (OR = 1.7, 95% CI, 1.15 to 2.55). The incidence of DGF was one of the independent
      risk factors for suboptimal graft function at one year (OR = 1.68, 95% CI, 1.14
      to 2.48), together with donor age of more than 50 years (OR = 2.39, 95% CI, 1.61
      to 3.57), female donor gender (OR = 1.99, 95% CI, 1.42 to 2.78), the occurrence
      of acute rejection episodes (OR = 2.66, 95% CI, 1.87 to 3.78), peak panel
      reactive antibodies of more than 50% (OR = 1.67, 95% CI, 1.15 to 2.47), and
      sharing of 1 to 3 versus 4 to 8 cross-reactive antigens groups (OR = 1.65, 95%
      CI, 1.09 to 2. 49). Moreover, DGF was one of the two independent risk factors for
      acute rejection episodes, but it had no independent effect on graft survival.
      CONCLUSION: Several risk factors for DGF were identified, of which a low
      recipient pretransplant mean arterial blood pressure, the transplantation of
      kidneys from female donors to male recipients, and a prolonged cold ischemia time
      are potentially avoidable. Although DGF is one of the several risk factors of
      acute rejection and suboptimal function at one year, it is not independently
      associated with an increased rate of graft loss.

PMID- 10916112
TI  - Increased intracellular reactive oxygen species in patients with end-stage renal
      failure: effect of hemodialysis.
AB  - BACKGROUND: Reactive oxygen species (ROS) have been implicated in various forms
      of cellular injury. ROS may cause cell damage and are involved in the
      pathophysiology of several diseases, including atherosclerosis and chronic
      inflammation. METHODS: Disturbances of intracellular ROS levels were investigated
      in 28 patients with end-stage renal failure. The intracellular ROS levels were
      measured in lymphocytes before and after hemodialysis using biocompatible
      membranes and were compared with those from 11 patients with end-stage renal
      failure, not yet on renal replacement therapy, and 27 healthy control subjects.
      ROS levels were measured spectrophotometrically using the intracellular dye
      dichlorofluorescin diacetate. RESULTS: The spontaneous production of ROS was
      significantly higher in lymphocytes from patients with end-stage renal failure
      compared with healthy control subjects (P < 0.01). The addition of 100 nmol/L
      phorbol-myristate-acetate (PMA) produced a significant increase of ROS, both in
      lymphocytes from patients with end-stage renal failure and healthy control
      subjects. The PMA-induced ROS increase was significantly higher in lymphocytes
      from patients with end-stage renal failure compared with healthy control subjects
      (P < 0.01). In patients with end-stage renal failure, not yet on renal
      replacement therapy, the PMA-induced ROS was also significantly higher compared
      with healthy control subjects. The PMA-induced ROS increases were significantly
      inhibited by catalase, but not by superoxide dismutase or the superoxide
      dismutase mimetic, tempol. PMA-induced ROS was significantly reduced by
      tyrphostin A51 in lymphocytes from patients with end-stage renal failure and from
      healthy control subjects (each P < 0.01), indicating the involvement of a
      tyrosine kinase-dependent pathway. In patients with end-stage renal failure, the
      spontaneous and the PMA-induced production of ROS was not significantly different
      before and after hemodialysis. CONCLUSIONS: Regular hemodialysis sessions using
      biocompatible membranes have no effect on the elevated intracellular ROS in
      patients with end-stage renal failure.

PMID- 10916113
TI  - Recombinant versus natural human 111In-beta2-microglobulin for scintigraphic
      detection of Abeta2m amyloid in dialysis patients.
AB  - BACKGROUND: We previously introduced scintigraphy with 131I-labeled beta2
      microglobulin (beta2m), purified from uremic hemofiltrate, that is, "natural"
      beta2m, to specifically detect beta2m-associated amyloidosis (Abeta2m) in
      hemodialysis (HD) patients. METHODS: To improve the safety and resolution of the
      scan, we covalently bound the chelator diethylenetriaminepentaacetic acid to
      natural beta2m to allow radiolabeling with 111In. In a second step, we generated
      and evaluated the usage of recombinant human beta2m (rhbeta2m) for scintigraphy.
      RESULTS: Using natural 111In-labeled beta2m, eight patients on HD for 0 to 17
      years, without evidence of Abeta2m, were scanned. Whole-body scintigraphy at 48
      to 72 hours postinjection revealed no significant tracer accumulation over joint
      regions. In contrast, nine patients on HD for 10 to 21 years with clinical,
      radiological, or histologic (N = 4) evidence of Abeta2m showed selective tracer
      uptake over various joint regions. Tracer accumulation in visceral organs, which
      could not be related to tracer elimination or metabolism, was not detected.
      Compared with the previous 131I beta2m scan, scintigraphy with 111In-labeled
      beta2m offered highly improved image contrast, increased sensitivity, and a 50 to
      70% reduction of the radiation exposure. Scanning with 111In-labeled recombinant
      human beta2m was performed in six patients: No significant tracer accumulation
      was observed over joint regions in two patients on short-term HD without evidence
      of Abeta2m; in contrast, local tracer accumulations similar to those observed
      with natural beta2m could be demonstrated in four long-term (10 to 27 years) HD
      patients with clinical, radiological, and histologic (N = 1) evidence of Abeta2m.
      CONCLUSION: Scintigraphy for Abeta2m with 111In-labeled rhbeta2m provides a
      homogenous and safe recombinant protein source and leads to enhanced sensitivity
      and lower radiation exposure.

PMID- 10916114
TI  - Bradykinin and nitric oxide generation by dialysis membranes can be blunted by
      alkaline rinsing solutions.
AB  - BACKGROUND: Bradykinin (BK) generation following the first contact of blood with
      the dialysis materials is thought to enhance hypersensitivity reactions (HSRs).
      Some of the effects of BK are mediated by nitric oxide (NO). We have recently
      reported that the pH of diluted blood modulates the kinin system. The present
      study was aimed to investigate the role of the pH of culture media and filter
      washing solutions and BK and NO generation, either in vitro and ex vivo. METHODS:
      BK was measured by a specific enzyme-linked immunosorbent assay (ELISA), and NO
      synthase (NOS) activity by 3H-citrulline production after incubation with 3H
      arginine and nitrites by using the Griess reagent. In in vitro experiments, NOS
      activity was detected in endothelial cells (ECs) cultured with graded BK
      concentrations at various pH values. Blood from 30 patients in regular dialysis
      was ex vivo circulated in one single passage through minifilters prerinsed with
      pH 7 or pH 8 phosphate buffer (PB) solutions. The out-flowing blood was tested
      for BK and nitrite content and was incubated with cultured ECs to evaluate its
      capacity to modulate NOS activity. RESULTS: BK induced in vitro a dose-dependent
      increase in NOS activity of ECs, which was mediated by tyrosine kinase
      phosphorylation. NO generation was enhanced at pH 7.2, which remained unchanged
      at pH 7.6. In ex vivo experiments, blood out-flowing after one passage on filters
      washed with pH 7 PB solutions had increased BK levels (P < 0.0001), increased
      nitrites (P < 0.05), and enhanced EC NOS activity (P < 0. 05) in comparison to
      data found when filters were washed with pH 8 PB. Only when the filters were
      rinsed with a solution at pH 7 did PAN DX and AN69 membranes show a distinct BK
      generation capability, and cuprophane a peculiar capability to enhance NOS. Such
      effects were prevented when dialyzers were prerinsed with pH 8 PB. Multiple
      regression analysis showed that the pH of the uremic blood was the driving factor
      for BK and NOS activation (r = 0.54, P < 0.02). CONCLUSIONS: BK and NO generation
      are modulated by environmental pH. Rinsing the blood and dialysate compartments
      of filters with an alkaline solution prior to use may mitigate the activation of
      mediators likely to be involved in some HSRs.

PMID- 10916116
TI  - EGF receptor activation by G-protein coupled receptors.

PMID- 10916115
TI  - Regression of left ventricular hypertrophy by lisinopril after renal
      transplantation: role of ACE gene polymorphism.
AB  - BACKGROUND: Cardiac complications are the main cause of death in renal
      transplantation (RT), and left ventricular hypertrophy (LVH) may play an
      important role in these patients. The unfavorable genotype of the angiotensin
      converting enzyme (ACE) gene has been associated with cardiovascular disease,
      including LVH. ACE inhibitors (ACEIs) reduce LVH, but little is known about the
      effects of ACEIs on LVH in RT patients with different insertion/deletion (I/D)
      genotypes of the ACE gene. METHODS: We prospectively studied 57 stable
      nondiabetic RT patients with hypertension and echocardiographic LVH as well as a
      functional graft for 69.5 +/- 5.6 months. Patients randomly received either
      lisinopril 10 mg/day (group A, N = 29; 5 were excluded due to reversible acute
      renal failure) or placebo (group B, N = 28) for 12 months. Echocardiography (M
      mode, 2-B, and color flow Doppler) was performed at baseline and 6 and 12 months
      later by the same examiner without previous knowledge of the genetic typing. The
      ACE genotype (I or D alleles) was ascertained by polymerase chain reaction (PCR;
      group A, DD = 10 and ID/II = 14; group B, DD = 15 and ID/II = 13). RESULTS: All
      patients maintained a good renal function (serum creatinine <2.5 mg/dL) during
      the follow-up and both groups received a similar proportion of antihypertensive
      drugs (beta-blockers 83 vs. 79%; Ca antagonists 66 vs. 68%; alpha1-adrenoreceptor
      antagonists 50 vs. 67%) during the study. As expected, mean arterial blood
      pressure and hemoglobin levels showed a higher percentage reduction in group A
      versus group B (-4 +/- 2.8 vs. 2.1 +/- 2.6%, P = 0.07, and -11.5 +/- 1.5 vs. -0.5
      +/- 2.3%, P < 0.01, respectively). Group A patients showed a significantly higher
      decrement in LV mass index (LVMI) than group B at the end of follow-up, after
      adjusting for age, baseline LVMI, time after grafting and changes in systolic
      blood pressure, renal function, and hemoglobin levels (group A, -9.5 +/- 3.5% vs.
      group B, 3 +/- 3.2%, P < 0.05). As a result, 46% of group A and only 7% of group
      B patients showed a reduction of LVMI >/=15% (P < 0.01). The beneficial effect of
      lisinopril on LVMI reduction was more evident in DD patients (placebo DD, 8.4 +/-
      4.1% vs. lisinopril DD, -7.2 +/- 5.3, P < 0.05), and a trend was observed in
      patients with other genotypes (placebo ID/II, 2.8 +/- 5.4% vs. lisinopril ID/II, 
      11.4 +/- 5%, P = 0.33). CONCLUSIONS: Lisinopril decreases LVM in renal transplant
      patients with hypertension and LVH, and the ACE gene polymorphism may predict the
      beneficial effect of this therapy. This finding may be important in targeting
      prophylactic interventions in this population.

PMID- 10916117
TI  - Body weight is a fluctuating parameter in hemodialysis patients.

PMID- 10916118
TI  - Organ commerce revisited.

PMID- 10916119
TI  - Comparison of survival data.

PMID- 10916120
TI  - Radiation nephropathy after bone marrow transplantation.

PMID- 10916121
TI  - Adolescent infectious disease challenges.
AB  - The 20th century brought incredible changes throughout the world and one of the
      most far-reaching results has been in the arena of public health, which,
      according to the CDC, means that people now live an average of 30 years longer.
      Despite these achievements, there are other diseases and health problems to
      handle. The expansion of world travel has led to increased chances for acquiring
      rare or exotic diseases. The shrinking world also means that people from other
      countries arriving in the U.S. bring the risk of new and re-emerging strains of
      old pathogens and other health problems. The ease of accessibility of
      antibacterial products means that their overuse and misuse continues to add to
      the ever-growing problem of drug-resistant bacteria. Gaps in adolescent
      immunization schedules and adolescent risk-taking behaviors are still at alarming
      levels. Large percentages of adolescents are either underinsured or uninsured,
      leading to delays in receiving effective and complete health care. Physicians
      have the chance to influence adolescent behaviors, and play and important role in
      helping to reduce these risks through informed decision making for these
      adolescents.

PMID- 10916122
TI  - Upper respiratory tract infections in adolescents.
AB  - While upper respiratory tract infections (URTIs) cause much infectious morbidity
      in infants and young children, adolescents are not immune to infections.
      Adolescents experience two to four episodes of viral nasopharyngitis annually. In
      addition to group A streptococcus (GAS), pharyngitis may occur with other
      streptococci, Arcanobacterium haemolyticum, Epstein-Barr virus, Neisseria
      gonorrhoeae, and other pathogens. Uvulits, typically in association with GAS,
      occurs occasionally. Peritonsillar abscess is the most common deep neck space
      infection seen in adolescents, but retropharyngeal and parapharyngeal abscesses
      also occur, causing major morbidity. Adolescents experience fewer cases of otitis
      media than younger children. Rhinosinusitis occurs commonly in adolescents,
      occasionally leading to chronic sinusitis and serious sequelae such as
      osteomyelitis. This article reviews the major URTIs likely to be encountered by
      physicians caring for adolescents. For each entity there is a brief description
      of the epidemiology, morbidity, microbiology, clinical and laboratory features,
      treatment, and prevention.

PMID- 10916123
TI  - Lower respiratory tract infections in adolescents.
AB  - Lower respiratory tract infections are an important cause of morbidity and
      occasional mortality in adolescents. This article reviews lower respiratory tract
      infections by anatomic location. Laryngotracheitis, tracheitis, bronchitis,
      pneumonia, and parapneumonic effusions are discussed. Specific viral, bacterial,
      mycoplasmal, and chlamydial etiologies are discussed. The epidemiology and
      clinical manifestations of lower respiratory tract infections in adolescents are
      presented according to anatomic site. Treatment for the spectrum of lower
      respiratory tract infections is also reviewed. Treatment options include
      supportive care, humidification, corticosteroids, antivirals, antibiotics, and
      appropriate drainage. Appropriate drainage of parapneumonic effusions includes
      thoracentesis, closed-tube thoracostomy, and surgery (thoracoscopy or
      thoracotomy). Imaging modalities include conventional radiography, computed
      tomography, and ultrasonography. Emphasis is placed on the common lower
      respiratory tract infections that affect the normal adolescent population.

PMID- 10916124
TI  - Infectious diseases of gastrointestinal tract in adolescents.
AB  - This article reviews the following gastrointestinal infections: esophagitis,
      gastritis, duodenitis including duodenal ulcers, and enteritis (gastroenteritis).
      The epidemiology, risk factors, microbiology and pathogenesis, diagnosis,
      treatment, morbidity/mortality, and prevention are discussed in relation to the
      most important pathogens. The symptoms and pathogenesis of esophagitis caused by
      Candida albicans and herpes simplex are contrasted with the symptoms of
      esophagitis caused by Helicobacter pylori and gastroesophageal reflux disease
      (GERD). The incidence of gastritis and gastric and duodenal ulcers caused by H.
      pylori is discussed. The treatment regimens of H. pylori infection recommended by
      the CDC are presented. Endoscopic findings in esophagitis, gastritis, and
      duodenal ulcers are presented and discussed. The difference in symptoms caused by
      viral agents (Norwalk virus), bacterial agents (enterotoxigenic E. coli), and
      parasites (Giardia lamblia and Cryptosporidium parvum) are compared and
      contrasted. The symptoms of infections of the terminal small bowel caused by
      Salmonella and Campylobacter jejuni and the symptoms of pure colonic infection,
      dysentery, caused by Shigella and enteroinvasive E. coli and Entamoeba
      histolytica are discussed. The treatment regimens for enteritis are presented.

PMID- 10916125
TI  - Acute and chronic viral hepatitis.
AB  - Viral hepatitis is the most common cause of acute and chronic hepatitis. The term
      viral hepatitis generally refers to infections resulting from one of the
      hepatotrophic viruses: hepatitis A, B, C, D, and E. The last 10 years have
      brought many important advances in understanding the epidemiology, pathogenesis,
      molecular biology, and immunoprophylaxis of infections caused by hepatotrophic
      viruses. Development of sensitive and specific immunoassays has enabled detection
      of specific agents. This has allowed for identification of infected patients and
      monitoring response to therapy. Additionally, serologic markers have allowed for
      isolation of contaminated blood products and a reduction in the spread of
      disease. The remaining challenge is the application of this knowledge to the
      treatment and prevention of viral hepatitis. This article explores the risk
      factors, epidemiology, microbiology, clinical and laboratory diagnosis,
      treatment, and prevention of the hepatotrophic viral infections.

PMID- 10916126
TI  - Adolescent urinary tract infections.
AB  - Urinary symptoms in adolescents are common, particularly in females. Urinary
      tract infections (UTIs) cause many of these symptoms. For uncomplicated UTIs,
      both lower and upper tract, therapy is straightforward. Commonly used antibiotics
      are trimethoprim/sulfamethoxazole (TMP/SMX), cefixime, and ciprofloxacin (off
      label use) for 3 days for lower tract infections and 10n14 days for upper tract
      infections. Adolescent UTIs are markers for sexual activity, just as UTIs in
      younger children are often markers for anatomic defects, e.g., congenital
      abnormalities. Adolescents with upper and lower UTIs often have concurrent sexual
      activity or a complication of that activity. Issues among adolescents with UTIs
      are more similar to those of young adults than to those of younger children. It
      is as important to counsel adolescents about sexual activity and its consequences
      as it is to treat the UTIs. All adolescents with UTIs should be queried for
      sexual activity; evidence of sexually transmitted diseases (STDs) should be
      sought; and counseling for STDs and responsible sexual activity is recommended.
      Complicated UTIs include those in patients who have grown into adolescence after
      a childhood of infections or who have anatomic abnormalities, recurrent
      infections, reflux and reflux nephropathy, spina bifida and neurogenic bladder,
      transplanted kidneys, diabetes, and urolithiasis. These patients require
      individualized medical programs, unique for their condition, history, and
      microbiology.

PMID- 10916127
TI  - Prevention and management of sexually transmitted diseases in adolescents.
AB  - This review focuses on the diagnosis and treatment of common sexually transmitted
      diseases (STDs) encountered among adolescents in the U.S. and other developed
      countries. Included are new recommendations for the treatment of primary and
      recurrent genital herpes, management of pelvic inflammatory disease, and a
      revised approach to the care of adolescent victims of sexual assault. Diagnosis
      begins with a classification based on major clinical findings: genital ulcers
      with lymphadenitis, urethritis, vaginal discharge, pelvic inflammatory disease,
      and male STD syndromes. Appropriate laboratory evaluation for each of these
      clinical presentations is detailed and treatment options are summarized.
      Preventive interventions along with suggestions for an approach to the
      preadolescent well care visit, generally scheduled at age 11n12 years, are
      offered. Routine preventive therapy after a sexual assault takes into account
      difficulty in follow-up and the need to reassure adolescents and their families
      that all prophylaxis for possible infection has been provided.

PMID- 10916128
TI  - Infectious exanthems and unusual infections.
AB  - Invasive disease due to group A beta-hemolytic streptococci (GABHS) can be
      divided into 3 categories of disease: streptococcal toxic shock syndrome
      (strepTSS), necrotizing fasciitis, and other invasive GABHS disease. Patients
      with strepTSS may have multiorgan failure within hours of presentation.
      Clindamycin and penicillin G should be used in combination for treatment of
      invasive GABHS disease. The mortality rate for menstrual staphylococcal toxic
      shock syndrome has decreased with early recognition and treatment, and removal of
      hyperabsorbent tampons from the market. Kawasaki syndrome (KS) is the most common
      cause of acquired heart disease in children in the U. S., and atypical forms have
      a higher mortality rate than typical KS. Hantavirus pulmonary syndrome is a
      zoonosis with an 80% mortality rate if the diagnosis is not made on first
      presentation and patients return to the hospital in shock. Children and
      adolescents with Lyme disease have an excellent prognosis and respond well to
      antimicrobial therapy. Cat scratch disease (CSD) is caused by Bartonella henselae
      and is transmitted by flea-infested kittens. CSD lymphadenopathy typically
      resolves spontaneously in 2n3 months; however, there is a 50% likelihood of
      resolution in 1 month if patients receive a 5-day treatment course with
      azithromycin.

PMID- 10916129
TI  - Human immunodeficiency virus infections in adolescents.
AB  - Human immunodeficiency virus (HIV) infection, once largely confined to
      adolescents with hemophilia, has come to involve the general adolescent
      population. Individuals younger than 22 years comprise up to 25% of the people
      newly infected with HIV. Unsafe sexual practices, intravenous drug abuse,
      homelessness, psychiatric disorders, and inadequate psychosocial support are only
      some of the factors that have contributed to the epidemic. Present data indicate
      that interventions have had a positive impact on adolescent behavior in
      preventing the continuing spread of the disease, but more needs to be
      accomplished before we consider the problem controlled. Although proper medical
      treatment and providing adequate psychological and social support to adolescents
      who are already infected constitute an important aspect of care, the true
      solution of the problem lies in altering the behavior and practices that lead to
      the acquisition of this infection.

PMID- 10916130
TI  - Musculoskeletal infections in adolescents.
AB  - Musculoskeletal infections are uncommon disorders in adolescents and represent
      unique diagnostic and therapeutic challenges to the clinician. The pathogenesis,
      treatment, and prognosis of many musculoskeletal infections vary markedly in
      children compared to adults based in part on behavioral differences, bone growth,
      and changing vascularity patterns. Since adolescents can exhibit manifestations
      of infection common to either age range, a familiarity with the differences is
      essential for successful management. This article reviews common musculoskeletal
      infections affecting normal adolescent population, but also includes special
      considerations. Hematogenous osteomyelitis and suppurative arthritis are reviewed
      in detail, including pathogenesis, etiology, signs and symptoms, diagnosis,
      laboratory tests, radiologic imaging, and treatment. Also discussed are
      contiguous osteomyelitis with and without vascular insufficiency, puncture wound
      osteomyelitis, vertebral osteomyelitis, osteomyelitis with sickle cell disease,
      chronic osteomyelitis, pyomyositis, acute bacterial myositis, and
      nonstreptococcal myonecrosis.

PMID- 10916131
TI  - Serious infections of the central nervous system: encephalitis, meningitis, and
      brain abscess.
AB  - Central nervous system infections in adolescents range from the diffuse
      cerebritis of encephalitis to the regional inflammation of meningitis, and very
      focal disease of brain abscess. Clinical presentations reflect this wide
      spectrum, with encephalitis primarily characterized by altered mental status,
      meningitis by fever, headache, and neck stiffness, and brain abscess manifesting
      localizing findings. Encephalitis and viral meningitis are frequently caused by
      the seasonal enteroviruses and arboviruses, while most adolescent bacterial
      meningitis is due to Neisseria meningitidis and Streptococcus pneumoniae. The
      microbiology of brain abscess reflects underlying host risk factors. Gram
      positive cocci are seen in patients with congenital heart disease, while
      respiratory flora including anaerobes are associated with sinus or otic disease.
      Lumbar puncture to characterize and culture the CSF remains the optimal test for
      the diagnosis and management of encephalitis and meningitis, while CT-guided
      needle biopsy may be both diagnostic and therapeutic for brain abscesses. New
      diagnostic tests include the use of PCR. A variety of safe and effective
      treatment regimens exists for most bacterial infections as well as for some
      herpesvirus infections. New vaccines are under study to further control bacterial
      meningitis.

PMID- 10916132
TI  - Current challenges in antibiotic resistance.
AB  - The striking, widespread increase in bacterial resistance to antibiotics is an
      issue of great concern. Worldwide emergence of antibiotic resistances in our
      common gram-positive coccal pathogens is probably the most serious problem we
      have in the realm of bacterial infections. The most important of these organisms
      are penicillin-resistant Streptococcus pneumoniae, vancomycin-resistant
      Enterococcus, and methicillin- (and now vancomycin-) resistant Staphylococcus
      aureus. Although known by the above names, all of these organisms are multidrug
      resistant. Beta-lactam and vancomycin resistances in gram-positive cocci are
      caused by altered cell wallnbinding sites with decreased affinity for the drug.
      Another serious problem is that of resistance in certain gram-negative bacilli
      due to extended-spectrum beta-lactamase production. These antibiotic resistances
      in common pathogens have made antimicrobial therapy of many infections extremely
      difficult or virtually impossible in some instances. The extensive, and often
      inappropriate, use of antibiotics in the U.S. and worldwide is the major factor
      in the emergence and spread of antimicrobial resistance. Microbial mechanisms,
      epidemiology, clinical importance, treatment, and prevention of these antibiotic
      resistance problems are discussed.

PMID- 10916133
TI  - Adolescent immunization.
AB  - The dramatic improvements achieved in the control of vaccine-preventable diseases
      in children have only been shared partially by adolescents and young adults, as
      today several million adolescents are not receiving the full complement of
      vaccines recommended by the Advisory Committee on Immunization Practices (ACIP).
      This article discusses the reasons for this problem and the tools to bridge this
      gap. In particular, medical societies and the Centers for Disease Control and
      Prevention (CDC) recommend a close assessment of the adolescentis immunization
      status between 11 and 12 years of age, inclusion of school immunization, and
      providing missing immunizations at any opportunity. The article also addresses
      other vaccines recommended for groups of adolescents with special needs,
      reporting information, and provides an update on the vaccines of the future.

PMID- 10916134
TI  - Tuberculosis and other infectious diseases in the adolescent immigrant.
AB  - Adolescent medicine physicians are frequently the initial contact for adolescents
      newly arriving in the U.S. and it is important that they recognize the needs of
      their patients. The adolescent immigrant may be encountered in a school-based
      health setting, private practice, community health center, or other health care
      settings. This article begins with a review of the categories of immigrants
      comprising the adolescent population. It gives an extensive review of
      tuberculosis among Mexican-American adolescents, detailing history, epidemiology,
      diagnosis, social factors, and treatment modalities. It further delineates the
      impact of Mexican tuberculosis control strategies on the practice of medicine in
      the U.S., and outlines preventive, diagnostic, and therapeutic strategies that
      should be followed in the adolescent immigrant. This article also reviews viral
      hepatitis in its multiple forms and its impact on the adolescent immigrant. It
      concludes by delineating prevention practices required for the adolescent
      immigrant and summarizes the interventions an initial contact physician should
      undertake upon encountering such adolescents.

PMID- 10916135
TI  - The antibody web
AB  - The internet has evolved to play a central role in the lives of immunologists.
      Powerful search engines facilitate the location of references or suppliers at the
      click of a mouse. Specialized websites provide reviews for many immunological
      topics and links for fast navigation to related information. This article
      highlights websites related to monoclonal and recombinant antibodies.

PMID- 10916136
TI  - Hybridoma technology: a view from the patent arena.
AB  - The patenting of biological molecules, such as hybridomas and monoclonal
      antibodies, has become an important issue in biology. While challenging cherished
      beliefs and practices of many biologists, it has been a central issue for
      hybridoma and monoclonal antibody research.

PMID- 10916137
TI  - With the benefit of hindsight.
AB  - The development of a method to produce monoclonal antibodies against a defined
      antigen has had profound impact in many branches of research and signalled a
      shift in the analysis of biological problems. This article describes the
      background to these developments and their important practical applications that
      impinge on the relationship between the world of basic science and commerce.

PMID- 10916138
TI  - Of mice and men: hybridoma and recombinant antibodies.
AB  - Thousands of mouse monoclonal antibodies have been produced from hybridomas over
      the past 25 years. The same technique can now be used to clone human antibodies
      from transgenic mice. Full-length antibodies and recombinant fragments engineered
      for various diagnostic and therapeutic applications can be obtained in reasonably
      large amounts after expression in mammalian cells, milk and plants.

PMID- 10916139
TI  - Natural and designer binding sites made by phage display technology.
AB  - In the past decade, the drive to develop completely human antibodies for human
      therapy has led to the development of phage display technology. This technology
      is able to deliver the ultimate in antibody engineering, that is, high-affinity
      fully human antibodies to any antigen of choice. Here, this application of phage
      display technology is reviewed, and the many other antibody-engineering avenues
      this technology offers are highlighted.

PMID- 10916140
TI  - Antibodies in diagnostics - from immunoassays to protein chips.
AB  - Antibodies are used extensively as diagnostic tools in a wide array of different
      analyses. Monoclonal and recombinant antibodies provide a never ending source of
      molecules and can produce endless possibilities for novel genetic constructs.
      Antibodies are still very much in vogue and are now also being used in microarray
      analysis of the proteome using protein chips. Here, recent opportunities
      presented by antibodies as diagnostic tools are reviewed.

PMID- 10916141
TI  - Monoclonal antibodies and the FACS: complementary tools for immunobiology and
      medicine.
AB  - The histories of monoclonal antibodies and the fluorescence activated cell sorter
      (FACS) are as closely intertwined as their current uses in biology and medicine.
      Here, Leonore Herzenberg, Stephen De Rosa and Leonard Herzenberg recount the
      meeting and the mating of these two technologies, whose offspring now populate
      clinical and research laboratories throughout the world.

PMID- 10916142
TI  - Immunotherapeutic perspective for bispecific antibodies.
AB  - Bispecific antibodies (BsAb) can, by virtue of combining two binding
      specificities, improve the selectivity and efficacy of antibody-based treatment
      of human disease. Recent studies underline the importance of both the 'anti
      trigger' and 'anti-target' modalities of BsAb for therapeutic efficacy. Several
      BsAb induce effective cytotoxicity as well as 'vaccine effects' in vivo. Here,
      Annemiek van Spriel and colleagues discuss how these results have catalysed
      renewed efforts to translate BsAb concepts into effective therapies.

PMID- 10916143
TI  - Antibody humanization: a case of the 'Emperor's new clothes'?
AB  - The antiglobulin response is perceived as a major problem in the clinical
      development of therapeutic antibodies. Successive technical developments such as
      chimeric, humanized and, now, fully human antibodies claim to offer improved
      solutions to this problem. Although there is clear evidence that chimeric
      antibodies are less immunogenic than murine monoclonal antibodies, little
      evidence exists to support claims for further improvements as a result of more
      elaborate humanization protocols.

PMID- 10916144
TI  - Clinical trials of antibody therapy.
AB  - Much of the 25 years since Kohler and Milstein first described making monoclonal
      antibodies (mAbs) has been spent trying to develop these reagents to treat human
      disease. Until recently, progress has been frustratingly slow and by 1994 only
      one mAb, anti-CD3 (OKT3), had been licensed for clinical use. In the past five
      years, however, the situation has changed dramatically, with numerous mAbs now
      showing clinical potential, and a further seven approved for human treatment.
      Furthermore, all indications are that this upward trend will continue, with a
      quarter of all new biological products currently undergoing clinical development
      being antibody based.

PMID- 10916145
TI  - Cross-reactivity and polyreactivity: the two sides of a coin.

PMID- 10916146
TI  - Building bridges from process R&D: from a customer-supplier relationship to full
      partnership.
AB  - A new and forward-looking way of running process R&D is introduced that
      integrates this core business in an efficient manner into the network of
      activities in different disciplines, which constitute the arena for the
      development of pharmaceutical products. The interfaces with surrounding areas are
      discussed in addition to the novel organizational principles implemented in
      process R&D and the workflow emanating from this. Furthermore, the Tollgate model
      used to keep track of the progress in a project and the pre-study concept are
      presented in detail. Finally, the main differences between operating modes in the
      past and in the future are highlighted.

PMID- 10916147
TI  - Intranasal vaccines: forthcoming challenges.
AB  - The mucosal epithelium of the upper respiratory tract constitutes an effective
      physical barrier to many pathogens. Its mucosal-associated lymphoid tissue is of
      particular importance for the protection and integrity of mucosal surfaces and
      the body's interior. Understanding the factors that influence the induction and
      regulation of mucosal immune responses will facilitate the design of vaccines
      capable of eliciting the appropriate type of protective immune response.

PMID- 10916148
TI  - Internalizing antibodies and targeted cancer therapy: direct selection from phage
      display libraries.
AB  - Antibody internalization is required for the success of many targeted
      therapeutics, such as immunotoxins, immunoliposomes, antibody-drug conjugates and
      for the targeted delivery of genes or viral DNA into cells. Recently, it has
      become possible to directly select antibody fragments from phage display
      libraries for internalization into mammalian cells. Here we review the
      therapeutic applications of internalized antibodies and describe how phage
      display enables the isolation of internalizing antibodies to novel or known
      targets.

PMID- 10916149
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- 10916151
TI  - Bo G. Malmstrom (1927-2000)

PMID- 10916150
TI  - Heparanase, a potential regulator of cell-matrix interactions.

PMID- 10916152
TI  - Maturation of cellular Fe-S proteins: an essential function of mitochondria.
AB  - Iron-sulfur (Fe-S) cluster-containing proteins perform important tasks in
      catalysis, electron transfer and regulation of gene expression. In eukaryotes,
      mitochondria are the primary site of cluster formation of most Fe-S proteins.
      Assembly of the Fe-S clusters is mediated by the iron-sulphate cluster assembly
      (ISC) machinery consisting of some ten proteins.

PMID- 10916153
TI  - 1H NMR visible lipids in the life and death of cells.
AB  - A functionally and metabolically interesting class of cell lipid can be observed
      by 1H nuclear magnetic resonance (NMR) spectroscopy in situ. These prominent
      resonances are not only associated with malignancy and cell death, but also act
      as heralds of benign processes, such as cell activation and proliferation.
      Originally, these NMR observations were explained with a membrane lipid
      microdomain model. However, recent studies have identified intracellular
      droplets, so called lipid bodies, as important contributors to these resonances.
      This finding bears novel implications for our understanding and assessment of
      lipid biochemistry in the life and death of cells.

PMID- 10916154
TI  - A novel motif for identifying rps3 homologs in fungal mitochondrial genomes.

PMID- 10916155
TI  - Simulations of ion channels--watching ions and water move.
AB  - Ion channels mediate electrical excitability in neurons and muscle. Three
      dimensional structures for model peptide channels and for a potassium (K+)
      channel have been combined with computer simulations to permit rigorous
      exploration of structure-function relations of channels. Water molecules and ions
      within transbilayer pores tend to diffuse more slowly than in bulk solutions. In
      the narrow selectivity filter of the bacterial K+ channel (i.e. the region of the
      channel that discriminates between different species of ions) a column of water
      molecules and K+ ions moves in a concerted fashion. By combining atomistic
      simulations (in which all atoms of the channel molecule, water and ions are
      treated explicitly) with continuum methods (in which the description of the
      channel system is considerably simplified) it is possible to simulate some of the
      physiological properties of channels.

PMID- 10916156
TI  - Control of elongation by RNA polymerase II.
AB  - The elongation stage of eukaryotic mRNA synthesis can be regulated by
      transcription factors that interact directly with the RNA polymerase II (pol II)
      elongation complex and by activities that modulate the structure of its chromatin
      template. Recent studies have revealed new elongation factors and have implicated
      the general initiation factors TFIIE, TFIIF and TFIIH, as well as the C-terminal
      domain (CTD) of the largest subunit of pol II, in elongation. The recently
      reported high-resolution crystal structure of RNA polymerase II, which provides
      insight into the architecture of the elongation complex, marks a new era of
      investigation into transcription elongation.

PMID- 10916157
TI  - Author correction

PMID- 10916158
TI  - Alternative pre-mRNA splicing: the logic of combinatorial control.
AB  - Alternative splicing of mRNA precursors is a versatile mechanism of gene
      expression regulation that accounts for a considerable proportion of proteomic
      complexity in higher eukaryotes. Its modulation is achieved through the
      combinatorial interplay of positive and negative regulatory signals present in
      the RNA, which are recognized by complexes composed of members of the hnRNP and
      SR protein families.

PMID- 10916159
TI  - Signaling networks linking integrins and rho family GTPases.
AB  - Integrins and Rho family GTPases function coordinately to mediate adhesion
      dependent events in cells. Recently, it has also become apparent that integrins
      regulate Rho GTPases and vice versa. Integrins and GTPases might therefore be
      organized into complex signaling cascades that regulate cell behavior.

PMID- 10916160
TI  - Tyrosinase/catecholoxidase activity of hemocyanins: structural basis and
      molecular mechanism.
AB  - The enzymes tyrosinase, catecholoxidase and hemocyanin all share similar active
      sites, although their physiological functions differ. Hemocyanins serve as oxygen
      carrier proteins, and tyrosinases and catecholoxidases (commonly referred to as
      phenoloxidases in arthropods) catalyze the hydroxylation of monophenols or the
      oxidation of o-diphenols to o-quinones, or both. Tyrosinases are activated in
      vivo by limited proteolytic cleavage, which might open up substrate access to the
      catalytic site. It has recently been demonstrated that if hemocyanins are
      subjected to similar proteolytic treatments (in vitro) they also exhibit at least
      catecholoxidase reactivity. On the basis of their molecular structures,
      hemocyanins are used as model systems to understand the substrate-active-site
      interaction between catecholoxidases and tyrosinases.

PMID- 10916162
TI  - DANTE: a workbench for sequence analysis.

PMID- 10916161
TI  - Diversity of transport mechanisms: common structural principles.
AB  - Traditionally, prokaryotic solute transport systems are classified into major
      groups based on the energetic requirement of the transport process. These include
      the secondary transporters that are driven by a proton or sodium motive force,
      and the ATP-binding cassette (ABC) primary transporters, which use the hydrolysis
      of ATP to fuel transport. These transporters are specified by entirely different
      architectures of polypeptides. Recently, transport systems have been discovered
      that are composed of combinations of distinct functional modules of both
      secondary and ABC transporters. These findings indicate that during evolution the
      combination of integral membrane transport proteins with either a periplasmic
      solute-binding protein or a cytosolic ATPase, or both, have resulted in distinct
      classes of transporters with unique architectures and properties.

PMID- 10916163
TI  - Disparity between dietary iron intake and iron status of children aged 10-12
      years.
AB  - Iron status was assessed in a representative sample of 188 adolescents living in
      a medium-sized city in Poland. Dietary intakes were evaluated using records of
      diet over a period of seven consecutive days. Subjects were considered to be iron
      deficient when two or more of the following parameters were abnormal: serum
      ferritin, transferrin saturation or mean corpuscular haemoglobin concentration.
      Based on this definition, the prevalence of iron deficiency in the investigated
      sample of children aged from ten to twelve years was 12.7%. Iron deficiency
      anaemia was defined using the following criteria: haemoglobin values less than
      12.0 g. dl (-1) in girls or less than 12.2 g. dl(-1) in boys, combined with an
      iron deficiency. With such a definition, the prevalence of iron deficiency
      anaemia in all subjects was 6.3%. Four boys (3.9%) and six girls (6.8%) were
      diagnosed as anaemic. The values for Hb in the anaemic boys ranged from 10.9 to
      12.2 g. dl (-1) and in anaemic girls from 8.7 to 12.0 g. (-1). It was found that
      the majority of the individuals studied had a dietary haem-iron intake lower than
      that recommended. No relationship was found between the level of serum ferritin
      and total iron and vitamin C dietary intake, but there was positive correlation
      between serum ferritin and intake of haem iron. A seven-day dietary history
      questionnaire correctly identified children at risk of iron deficiency anaemia.

PMID- 10916164
TI  - EEG and implanted sources in the brain.
AB  - Localisation procedures are based on models of the EEG that are relatively
      simple. The models are based on assumptions and choices of parameters that can be
      mistaken. Thus, it is crucial to validate the localisation procedures used in
      EEG. One of the options is to use the data obtained with electrodes that are
      implanted within the brain of an epileptic patient as part of the pre-surgical
      evaluation. When one of two neighbouring electrodes is used as a current source
      and the other as a current sink this can be regarded as a current dipole. The
      current injected has to be below the threshold for activation of cells. The
      position of this dipole can be deduced from magnetic resonance or X-ray images.
      The current dipole gives rise to a potential distribution at the scalp that can
      be measured by EEG. The measurements can be compared with the potential
      distribution that is calculated in a forward computation. Another method is to
      use the measured potential at the scalp to localize the source and to compare the
      result with the actual position of the dipole. In this paper the measured
      potential distributions at the scalp due to implanted dipoles were used to
      evaluate different volume conductor models. Since intracerebral and subdural
      electrodes were introduced through trephine holes over the fronto-central areas,
      and the diameter of the holes was rather large, approximately 23 mm, special
      effort was put into modelling the skull. Two important assumptions could be
      validated in this study: the electric currents within the head are Ohmic and a
      dipole can be used to model the induced electric activity of pairs of contacts on
      subdural electrodes or intra cerebral electrodes.

PMID- 10916165
TI  - An explanation of gastric hypersecretion in the pylorus-ligated rat.
AB  - The hypersecretion of gastric acid in the pylorus-ligated rat has been shown to
      be of vagal origin. The present series of experiments were performed to identify
      the stimulus. The pyloric sphincter was ligated in a series of Sprague Dawley
      rats. Along with pylorus ligation, various other surgical manipulations were
      performed. Intestinal obstruction by ligation approximately 20 cm aboral to the
      cecum reduced unstimulated gastric secretion in the pylorus-ligated rat. However,
      perfusion of the lower small intestine with bicarbonate (143 mEq/L) stimulated
      secretion. Perfusion with either saline or deoxycholic acid (20 mEq/L) did not
      alter secretion. This supports a role for bicarbonate in the hypersecretion of
      gastric acid in the pylorus-ligated rat. The reflex appears to involve the
      myenteric plexus, since section of the pylorus seemed to attenuate gastric
      secretion. Plasma from animals with pylorus ligation, either alone or with
      intestinal ligation, equally inhibited gastric secretion. This suggests that
      while some factor inhibiting gastric secretion may be present, it appears to be
      unrelated to pylorus ligation.

PMID- 10916166
TI  - Circadian phase estimation of chronic insomniacs relates to their sleep
      characteristics.
AB  - The significance of the phase of circadian rhythmicity for the diagnosis of sleep
      disturbance was investigated in a group of 80 chronic insomniacs (59 females;
      mean age 34.8, range 18-59 years). In order to stay close to common clinical
      practice, data were collected by means of two-week sleep diaries in combination
      with repeated measurements of subjective alertness and oral temperature. Special
      measures were taken to minimize the impact of masking upon the temperature
      measurements. In addition, wrist activity was monitored for an overlapping period
      of 11 days. Measurements of oral temperature and subjective alertness were fitted
      with 3 (rd) -degree polynomials, for which the peak times (times of maximum) were
      identified. Principal Components Analysis of these peak times and the times of
      bed-in and wake-up for all subjects revealed that the phase estimates for the
      alertness and the sleep-wake rhythms had a strong interrelationship, which was
      independent from the temperature phase. Using the 25- and the 75-percentiles of
      the frequency distribution of the temperature peak times as boundaries, the
      subjects were classified into early (N = 18), middle (N = 37) and late (N = 19)
      temperature phase subgroups, which had mean peak times of 14:08 h, 17:43 h and
      20:09 h, respectively. Comparisons between the early phase and the late phase
      subgroups showed that a significant overall MANOVA effect was mainly due to
      differences in total sleep time (early < late) as calculated from the log, and to
      differences in the mean nocturnal actigraphic count (early> late). Moreover, the
      subjective estimates of sleep latency (early < late) and wake after sleep onset
      (early > late) tended to differ between the two subgroups. The main result of
      this study, i.e., that insomniacs with a relatively advanced temperature phase
      had a relatively shorter and more restless sleep, while insomniacs with a
      relatively delayed temperature phase tended to experience a relatively long sleep
      latency, supports the conclusion that the addition of oral temperature
      measurements to a sleep/wake log extends its diagnostic and therapeutic
      applicability.

PMID- 10916168
TI  - Localisation of epidermal growth factor receptor in the quail ovary.
AB  - The present study focuses on the distribution of EGFR in the follicular and
      stromal compartments of the Japanese quail (Coturnix coturnix japonica) ovary,
      using immunohistochemical methods and a histological ligand binding assay. EGFR
      was predominantly present in granulosa cells during each stage of the
      folliculogenesis. Furthermore, EGFR was also detected in thecal cells and in
      oocytes. In some cells of the vascular endothelium, of the ovarian smooth muscle,
      and of the surface epithelium, the presence of EGFR was detected as well. The
      presence of EGFR allows to formulate the hypothesis that EGFR-ligands are
      involved in the autocrine and/or paracrine regulation of oocyte maturation and of
      folliculogenesis in the quail, and possibly in all birds.

PMID- 10916167
TI  - Effects of physical exercise on liver ATP levels in fasted and phosphate-injected
      rats.
AB  - The purpose of the present study was to investigate the effects of exercise (30
      min, 23 m/min, 0% grade) on the hepatic levels of ATP in fasted
      adrenodemedullated rats, with an intraperitoneal injection of sodium phosphate
      (Na (2) PO (4 ), 0.91 mM) or saline (NaCl). Sodium phosphate was injected to
      determine if the postulated decrease in liver ATP during exercise may be changed
      by providing an excess of phosphate. At the end of exercise, a piece of liver was
      rapidly freeze clamped and used for the enzymatic determination of ATP levels.
      Liver ATP, in saline-injected rats, was significantly (P < 0.05) decreased by
      fasting, compared to fed rats (&Xscr; +/- SE: 3. 21 +/- 0.2 vs 2.86+/- 0.2
      micromol/g). Exercise in fasted rats decreased even more the ATP response in
      liver (2.58 +/- 0.14 micromol/g). Injection of Na (2) PO (4) did not
      significantly (P > 0. 05) alter the pattern of ATP response following these 3
      conditions (3.35 +/- 0.14 vs 3.0 +/-0.12 vs 2.57 +/- 0.1 micromol/g), ATP levels
      being significantly (P <0.05) decreased by the fast and the exercise in the
      fasted state. Fasting and exercise resulted in a significant (P < 0.05) decrease
      in liver glycogen and plasma glucose concentrations and an increase in free fatty
      acid levels in both NaCl- and Na (2 )PO (4) -injected groups. In both injection
      conditions, beta-hydroxybutyrate and peripheral insulin concentrations were
      respectively, increased and decreased (P < 0.05) by fasting, while norepinephrine
      and portal glucagon were decreased (P > 0.05) following exercise. The main effect
      of the injection of Na ( 2) PO (4) was a stimulation (P < 0.05) of peripheral
      glucagon response following exercise. It is concluded that exercise results in a
      decrease in liver ATP levels even in fasted rats and that this decrease is not
      corrected by Na (2 )PO( 4) administration. The decreased liver ATP levels might
      be involved in the metabolic adaptations to exercise.

PMID- 10916169
TI  - Identification of tuberculo-ventral neurons in the polymorphic layer of the rat
      dorsal cochlear nucleus.
AB  - The tuberculo-ventral tract represents a short nervous circuit within the
      auditory cochlear nuclei. Tuberculo-ventral neurons of the dorsal cochlear
      nucleus send isofrequency inhibitory inputs to bushy cells of the ventral
      cochlear nucleus. Injection of wheat germ agglutinin conjugated to horseradish
      peroxidase into the rat ventral cochlear nucleus, labelled tuberculo-ventral
      neurons retrogradely in the deep polymorphic layer of the ipsilateral dorsal
      cochlear nucleus. Five to 20% of the perimeter of these cells was covered by
      synaptic boutons, most of which contained flat and pleomorphic vesicles. These
      boutons contained glycine and sometimes GABA. Occasional small axo-somatic
      boutons contained round vesicles and were immunonegative for both glycine and
      GABA. This study shows that the synaptic profile of tuberculo-ventral neurons is
      different from that of other medium-size glycinergic neurons within the
      polymorphic layer or more superficial regions of the dorsal cochlear nucleus like
      cartwheel neurons. In fact the latter mostly receive boutons that contain
      pleomorphic vesicles.

PMID- 10916170
TI  - Expression of polysialic acid, alpha- and beta-cantenins in adult toad testis in
      hibernation stage and after gonadotrophin--releasing hormone (GnRH) treatment.
AB  - The Polysialic Acid (PSA), glycosydic moiety of the Neural Cell Adhesion Molecule
      (N-CAM), and alpha- and beta-Catenins, which mediate interaction between
      Cadherins and cytoskeletal proteins, participate in cell adhesion phenomena in
      numerous organs and tissues. We have performed an immunohistochemical analysis,
      in hibernating toad testis and in GnRH-reactivated hibernating animals. In
      hibernating toads we could demonstrate PSA-immunoreactivity (PSA-IR) within the
      seminiferous tubules, in clusters of primary spermatocytes, spermatids and
      spermatozoa, in follicular and Sertoli cells. PSA-IR was seen in peritubular,
      Leydig and efferent duct cells. In GnRH-treated toads PSA-IR persists in primary
      spermatocyte groups. alpha-Catenin is localized in the basal laminae of
      seminiferous tubules and in Leydig cells of hibernating toads. This did not
      change after hormonal treatment. In hibernating toads, beta-Catenin was detected
      only in Leydig cells and within seminiferous tubules on basal spermatocystes and
      limiting spermatozoa clusters. In GnRH-treated toads, the beta-Catenin-IR was
      less intense in Leydig cells and vanished within seminiferous tubules.

PMID- 10916171
TI  - Skin morphology and function in Xenopus laevis exposed to a saline environment
      for up to one week.
AB  - This study evaluated the skin adaptation response in Xenopus laevis to short- and
      medium-term stays (24 h, 48 h, 7 days) in brackish water. Morphological,
      histochemical, histoenzymological (alkaline phosphatase, carbonic anhydrase) and
      electrophysiological (short-circuit current, resistance) characteristics were
      examined. The results show that animals adapt to brackish water, implementing a
      variety of short and medium-term morphofunctional modifications of the epidermis
      and skin glands. These modifications form part of the defence mechanisms needed
      to protect the animal from an excess increase in the saline concentration of
      internal fluids.

PMID- 10916172
TI  - Microfilaments in regenerating cells of rabbit cornea: immunological and
      ultrastructural observations.
AB  - The role of myosin-like protein in regenerating and proliferating corneal cells
      following a standard alkali-injury in the rabbit eye has been studied.
      Microfilaments were observed by conventional transmission electron microscopy
      (T.E.M.) in injured epithelium and in fibroblasts. Typical microfilament bundles
      with electron dense structures and with stress fibers were evident. The presence
      of myosin-like proteins was demonstrated by means of immunochemical and
      autoradiographical techniques. Both epithelial cells and fibroblasts bind
      antimyosin-like antibodies (AMA). The same cells studied with the E.M. showed
      bundles of microfilaments in the cortical areas of their cytoplasm in
      correspondence with the same side of fluorescent or labelled AMA. The
      immunochemical and ultrastructural results suggest that both cells are able to
      produce in vivo movements involved in morphogenetic phenomena. Therefore, these
      structures play a role in post-traumatic corneal regeneration.

PMID- 10916173
TI  - Morphological study of the heart innervation of bats Myotis daubentoni and
      Eptesicus serotinus (Microchiroptera: Vespertilionidae) during hibernation.
AB  - The capability of bats to have heart rates fewer than 10 beats/min during
      hibernation and greater than 700 beats/min during flight surprises biologists and
      cardiologists. Cardioacceleration of hibernating bats is considered to be a
      function of their intracardiac nervous system. In the present study we
      investigated the morphology of the heart innervation of ten M. daubentoni and
      four E. serotinus bats during their natural hibernation in order to determine
      which intracardiac structures may be involved in cardioacceleration during their
      short-term (in av. 15-30 min) arousal from hibernation. The primary conclusions
      were as follows: (1) The innervation pattern of bats differs from many mammals in
      that bats have: (a) a subepicardiac nerve plexus which is vastly developed and
      contains a large number of intrinsic ganglia on both atria and ventricles, and
      (b) very small diameter axons within the unmyelinated nerve fibres, from 0.15 to
      0.7 microm. (2) During hibernation an intercellular space of the sinoatrial node
      of M. daubentoni bats was in part filled with a cottony substance which can
      presumably be considered to be a temporary barrier between the conductive
      cardiomyocytes and nerve fibres. (3) In the hibernating bats, the acetylcholine
      vesicles were aggregated in the synaptic bulbs away from the presynaptic
      membrane. Possibly, the aggregation of the acetylcholine vesicles is capable of
      modifying cholinergic influences on the heart activity of hibernating bats. (4)
      The dense cores of catecholamine synaptic vesicles within, adrenergic axon
      terminals were seldomly observed in hibernating bats. Therefore, catecholamines
      probably do not play a crucial role in the cardioacceleration of hibernating
      bats.

PMID- 10916174
TI  - Human kappa-like expression in the axial organ of the sea star Asterias rubens
      (Echinoderma).
AB  - The axial organ of sea star Asterias rubens is a primitive immune organ which in
      certain conditions produces an antibody-like factor (ALF). This A.L.F. presents
      homologies with the human kappa chain. The ALF could be composed of many kappa
      chains devoid of any disulfide bond. The ontogeny of kappa expression was
      studied. Just after metamorphosis of the sea star, certain mesodermic cells which
      become axial organ cells express human kappa-like activity.

PMID- 10916175
TI  - The ambiguity and the exigency: clarifying 'standard of care' arguments in
      international research.
AB  - This paper examines the concept of a 'standard of care' as it has been used in
      recent arguments over the ethics of international human-subjects research. It
      argues that this concept is ambiguous along two different axes, with the result
      that there are at least four possible standard of care arguments that have not
      always been clearly distinguished. As a result, it has been difficult to assess
      the implications of opposing standard of care arguments, to recognize important
      differences in their supporting rationales, and even to locate the crux of the
      disagreement in some instances. The goal of the present discussion, therefore, is
      to disambiguate the concept of a 'standard of care' and to highlight the areas of
      genuine disagreement among different standards. In the end it is argued that one
      standard of care argument in particular is more complex than either its
      proponents or its critics may have recognized and that understanding this
      possibility opens up a potentially promising avenue of inquiry that remains to be
      carefully explored.

PMID- 10916176
TI  - Freedman's 'clinical equipoise' and sliding-scale all-dimensions-considered
      equipoise'.
AB  - It is often claimed that a clinical investigator may ethically participate (e.g.,
      enroll patients) in a trial only if she is in equipoise (if she has no way to
      ground a preference for one arm of the study). But this is a serious problem, for
      as data accumulate, it can be expected that there will be a discernible trend
      favoring one of the treatments prior to the point where we achieve the trial's
      objective. In this paper, I critically evaluate Benjamin Freedman's 'clinical
      equipoise' solution to this dilemma. I argue that Freedman actually puts forth at
      least two distinct contrasts--one in terms of community vs. individual equipoise,
      and another concerning clinical vs. theoretical equipoise--and that neither of
      them resolves the dilemma. I then make a proposal for a more adequate account of
      how to think about the circumstances under which entering subjects in trials
      would be justified--a 'sliding-scale equipoise' that arises out of a discussion
      of patients' values.

PMID- 10916177
TI  - Good enough for the Third world.
AB  - Over the past two years, much has been made by some governments and the media
      about the possible callous and racist distribution of Quinacrine by two Americans
      to sterilize women in the Third World. The main criticism of the practice is that
      though Quinacrine is unapproved by the developed world's health regulatory
      agencies for this particular use in the developed world due to inadequate testing
      for long-term side effects, it is used on defenseless women in the developing
      world.I argue that the distribution of unapproved medical and other products is
      morally permissible if it satisfies two conditions: agent-centered utilitarianism
      and Kant's Categorical Imperative. Roughly, I contend that if the situation will
      probably improve and no one is treated as a mere means, then it is ethical either
      to give or to sell the products to those who choose to have them, regardless of
      where in the world they live.

PMID- 10916178
TI  - Of maize and men: reproductive control and the threat to genetic diversity.
AB  - The genetic diversity argument (GDA) is one of the most commonly voiced
      objections to advances in reproductive and genetic technologies. According to the
      argument, scientific and technological developments in the realm of genetics and
      human reproduction will lead to lower genetic diversity, which will threaten the
      health and survivability of the human population. This discussion explicates and
      analyzes the GDA and challenges its empirical assumptions. It also discusses the
      possible significance of the GDA in our overall thinking about genetics and human
      reproduction and examines two proposals for preserving "useful" genes.

PMID- 10916179
TI  - Jewish bioethics?
AB  - "Jewish Bioethics" as currently formulated has been criticized as being of
      parochial concern, drawing on obscure methodology, employing an authoritarian
      (and, to the modern mind, unintelligible) method of discourse and as being of
      little relevance to the wider community. We analyze Jewish bioethics in terms of
      rule and principle theory and demonstrate that it is based on rational
      consideration and reproducible reasoning. This approach allows methodological and
      terminological translation into a Western method of discourse that, in turn, has
      much to contribute to clarifying underlying principles and methods of application
      of modern bioethics.

PMID- 10916180
TI  - Mind-body dualism and the biopsychosocial model of pain: what did Descartes
      really say?
AB  - In the last two decades there have been many critics of western biomedicine's
      poor integration of social and psychological factors in questions of human
      health. Such critiques frequently begin with a rejection of Descartes' mind-body
      dualism, viewing this as the decisive philosophical moment, radically separating
      the two realms in both theory and practice. It is argued here, however, that many
      such readings of Descartes have been selective and misleading. Contrary to the
      assumptions of many recent authors, Descartes' dualism does attempt to explain
      the union of psyche and soma - with more depth than is often appreciated. Pain
      plays a key role in Cartesian as well as contemporary thinking about the problem
      of dualism. Theories of the psychological origins of pain symptoms persisted
      throughout the history of modern medicine and were not necessarily discouraged by
      Cartesian mental philosophy. Moreover, the recently developed biopsychosocial
      model of pain may have more in common with Cartesian dualism than it purports to
      have. This article presents a rereading of Descartes' mental philosophy and his
      views on pain. The intention is not to defend his theories, but to re-evaluate
      them and to ask in what respect contemporary theories represent any significant
      advance in philosophical terms.

PMID- 10916182
TI  - Homozygous and heterozygous gly-188-Arg mutation of the rhodopsin gene in a
      family with autosomal dominant retinitis pigmentosa.
AB  - Autosomal dominant retinitis pigmentosa (adRP) may be caused by point mutations
      in the rhodopsin gene in up to 20% of Spanish families. Most of the rhodopsin
      mutations causing adRP have been reported in the heterozygous state. We describe
      a patient with adRP who is homozygous for a missense mutation at codon 188 in the
      second intradiscal domain of rhodopsin. All her sons are heterozygous for the
      mutation and show an RP phenotype suggesting complete penetrance for this
      mutation. The homozygous carrier of the mutation Gly-188-Arg in the rhodopsin
      gene showed a later subjective onset of symptoms than the heterozygotes,
      suggesting that the photoreceptor degeneration induced by the mutation is not
      dramatically influenced by mutant allele dosage.

PMID- 10916181
TI  - Full-field ERG in patients with Batten/Spielmeyer-Vogt disease caused by
      mutations in the CLN3 gene.
AB  - PURPOSE: To investigate, using full-field ERG, the retinal function in patients
      with Batten/Spielmeyer-Vogt disease caused by mutations in the CLN(3) gene.
      METHODS: Batten disease status of five patients was confirmed by the presence of
      vacuolated lymphocytes in peripheral blood and the identification of mutations in
      the Batten disease gene (CLN(3)). Visual acuity, fundus appearance, and full
      field ERG were examined in all patients (age 4-19 years). The examination was
      repeated in one patient after 16 months. RESULTS: Three unrelated patients were
      homozygous for the most common mutation in CLN(3), the 1.02 kb deletion; two
      patients (sisters) were heterozygous for the 1.02 kb deletion and an as yet
      unidentified mutation in the CLN(3) gene. Full-field ERG recordings in all five
      patients demonstrated no rod responses and only small remaining cone responses,
      which could be detected with 30 Hz-flicker stimulation. Re-examination of a six
      year-old girl after 16 months revealed a fast progression of the retinal
      degeneration. CONCLUSION: Full-field ERG recordings in Batten disease patients,
      both homozygous and heterozygous for the 1.02 kb deletion in the CLN( 3) gene,
      confirm retinal degeneration to be severe, widespread, and with a rapid
      progression early in the disease course. The onset of visual failure may be
      delayed when compared to the classic disease course, particularly in patients who
      are not homozygous for the most common CLN(3) mutation, a 1.02 kb deletion. In
      that case, the disease progression in terms of other symptoms may also be further
      delayed.

PMID- 10916183
TI  - Visual phenotype in patients with Arg41Gln and ala196+1bp mutations in the CRX
      gene.
AB  - Our aim was to describe the visual function characteristics of affected members
      from two unrelated families with different dominant mutations in the CRX gene.
      Standard full-field ERGs and high-intensity a-wave series were obtained. In
      addition, in most subjects, dark-adapted (DA) thresholds, color vision function
      (arrangement tests), and static perimetry were assessed. A point mutation in
      codon 41 of the CRX gene (Arg41Gln) was identified in family members from the
      RFS087 family who were tested on several occasions since 1983. Depending on age,
      affected members showed varying degrees of acuity loss, normal or slightly
      elevated DA thresholds, reduced cone a- and b-wave amplitudes, normal or
      minimally delayed cone b-wave implicit times, and normal rod and cone
      phototransduction gain parameters. An insertion mutation (Ala196+1bp) was found
      in two members of another family (RFS014). Affected members showed reduced visual
      acuity, normal or slightly elevated DA thresholds, relatively preserved rod ERG
      and substantially reduced or undetectable cone ERG, and normal rod
      phototransduction gain parameters. The Arg41Gln was associated with a late-onset,
      slowly progressing mild form of cone-rod dystrophy with cone loss but preserved
      rod and cone sensitivity until later in life. The Ala196+1bp mutation was
      associated with an early-onset, severe form of cone-rod dystrophy similar to that
      described in the original CORD2 family (Evans et al., Arch Ophthalmol
      1995;113:195-201).

PMID- 10916184
TI  - An unusual central retinal dystrophy associated with ichthyosis vulgaris.
AB  - A number of ichthyosis syndromes may have retinal abnormalities such as the
      retinitis pigmentosa-like diffuse rod-cone dystrophy in Refsum's syndrome and the
      maculopathy in Sjogren-Larsson syndrome. We present two sisters who have an
      unusual, almost identical, bilaterally symmetric central retinal dystrophy
      associated with ichthyosis vulgaris in the absence of other systemic disorders.
      We believe that this dystrophy has not been previously described in patients with
      any of the known varieties of ichthyosis.

PMID- 10916185
TI  - Mutations in the third exon of the MYOC gene in spanish patients with primary
      open angle glaucoma.
AB  - Primary open angle glaucoma (POAG) is the second most common cause of blindness
      in developed countries. It is an optic neuropathy in which a degeneration of the
      retinal ganglion cells causes a characteristic excavation in the optic disc.
      Several loci have been identified to be responsible for different types of
      glaucoma, including the MYOC gene located on chromosome 1. In this work, six
      mutations have been identified in the third exon of the MYOC gene in patients
      with POAG. We studied 79 Galician patients with chronic POAG glaucoma and 90
      control individuals from the same general population. We identified six
      mutations, including three novel ones. Two of the six mutations were considered
      to be polymorphisms, while the other four met the criteria for pathogenicity in
      this disease as they altered the amino acid sequence and were found in one or
      more patients with glaucoma and in less of 1% of the control population. These
      mutations were detected in eight patients suffering from POAG (7.5%) and in two
      people from the control population (2.2%). POAG can be due to mutations in the
      myocilin gene (MYOC) on chromosome 1. The glaucoma phenotype associated with this
      gene may vary from a juvenile severe form to a late-onset chronic open angle
      glaucoma.

PMID- 10916186
TI  - Apple peel atresia in association with bilateral colobomatous malformation of the
      optic nerve heads, dysmorphic features, and learning disability - a new syndrome?
AB  - Apple peel atresia of the small bowel is a rare congenital cause of intestinal
      obstruction. This case report describes a male patient with apple peel atresia
      and bilateral colobomatous malformation of the optic nerve heads in association
      with dysmorphic features and learning disabilities. In the absence of a positive
      family history, we propose that this collection of clinical findings could be due
      to a new dominant mutation or chromosomal microdeletion.

PMID- 10916187
TI  - Prevalence of 2314delG mutation in Spanish patients with Usher syndrome type II
      (USH2).
AB  - The Usher syndrome (USH) is a group of autosomal recessive diseases characterized
      by congenital sensorineural hearing loss and retinitis pigmentosa. Three
      clinically distinct forms of Usher syndrome have so far been recognized and can
      be distinguished from one another by assessing auditory and vestibular function.
      Usher syndrome type II (USH2) patients have congenital moderate-to-severe
      nonprogressive hearing loss, retinitis pigmentosa, and normal vestibular
      function. Genetic linkage studies have revealed genetic heterogeneity among the
      three types of USH, with the majority of USH2 families showing linkage to the
      USH2A locus in 1q41. The USH2A gene (MIM 276901) has been identified: three
      mutations, 2314delG, 2913delG, and 4353-54delC, were initially reported in USH2A
      patients, the most frequent of which is the 2314delG mutation. It has been
      reported that this mutation can give rise to typical and atypical USH2
      phenotypes. USH2 cases represent 62% of all USH cases in the Spanish population,
      and 95% of these cases have provided evidence of linkage to the USH2A locus. In
      the present study, the three reported mutations were analyzed in 59 Spanish
      families with a diagnosis of USH type II. The 2314delG was the only mutation
      identified in our population: it was detected in 25% of families and 16% of USH2
      chromosomes analyzed. This study attempts to estimate the prevalence of this
      common mutation in a homogeneous Spanish population.

PMID- 10916188
TI  - Expanded normative data for the Mattis Dementia Rating Scale for use with urban,
      elderly medical patients.
AB  - Normative data for the Mattis Dementia Rating Scale (MDRS), stratified by age and
      education, are provided for use with older adults (ages 61-94) in urban medical
      settings. Age and education accounted for the greatest amount of variance in MDRS
      performance. Gender and race were also associated with total MDRS scores, though
      to a lesser extent. The present normative data are more appropriate for use with
      older patients seen in urban medical settings than normative data obtained from
      samples of better-educated, relatively healthy, Caucasian adults. This study
      provides additional evidence of the significant influence of age and education on
      MDRS total score (MDRS-T) performance, and highlights the importance of matching
      an examinee's demographic background to the normative sample with which his or
      her test score is being compared. Careful consideration of this match is likely
      to lead to more accurate diagnostic conclusions and potentially improved patient
      care.

PMID- 10916189
TI  - Psychometric properties of the Halstead Category Test.
AB  - Using the Kuder-Richardson formula 20 (KR-20) corrected for item difficulty, the
      internal consistency reliability of the Halstead Category Test (HCT) was
      calculated for a sample (N = 398) of normal patients and volunteers, diffusely
      brain-damaged patients, and undiagnosed patients sent for neuropsychological
      assessment. The HCT Total Score reliability was.9716 and the subtest
      reliabilities ranged from.4587 to.9590. An item analysis found that most of the
      test items, except for those from Subtests I and II, were within established
      criteria for item difficulty and the discrimination index.

PMID- 10916190
TI  - Effects of test administration order on children's neuropsychological
      performance: emerging one-word expressive and receptive language skills.
AB  - Differences in neuropsychological performance associated with specific test
      presentation sequences have been reported in adults. However, these effects have
      received little attention in children. The EOWPVT-R, a measure of one-word
      expressive language, and the PPVT-R, a measure of receptive language, were
      administered to 6- to 14-year-olds (control [n = 17] and experimental [n = 22]
      groups) in a counterbalanced fashion to investigate the potential effects of test
      presentation sequence on neuropsychological performance. Group findings were not
      evidenced subsequent to variation in test administration sequence. In contrast,
      order of test presentation revealed differences in performance. Administration of
      the PPVT-R prior to the EOWPVT-R resulted in enhanced EOWPVT-R expressive
      language scores in both groups of participants. Presentation of the PPVT-R after
      the EOWPVT-R did not affect performance. Applied and theoretical implications
      associated with these findings are discussed.

PMID- 10916191
TI  - Clinical utility of the Normative Studies Research Project test battery among
      vascular dementia patients.
AB  - The purpose of the present study was to examine the clinical utility of the
      Normative Studies Research Project test battery for detecting dementia with a
      known vascular component. The study compared 65 patients who had both suffered a
      stroke and met the DSM-IV criteria for dementia with 86 older medical patients
      who were cognitively intact. Multivariate analysis of covariance results
      demonstrated that these two groups had significantly different means on tests
      within the battery even after controlling for the influence of demographic
      variables. Logistic regression results demonstrated positive predictive value of
      81.36%, negative predictive value of 85. 23%, and an overall correct
      classification rate of 83.67%.

PMID- 10916192
TI  - PPVT-R as an estimate of premorbid intelligence in older adults.
AB  - The Peabody Picture Vocabulary Test-Revised (PPVT-R) was examined as an estimate
      of premorbid intelligence in a clinical sample of elderly patients (N = 150)
      undergoing clinical neuropsychological evaluation. PPVT-R standard scores were
      compared across grossly cognitively intact, mildly/moderately and severely
      impaired groups of patients, and compared to a short form of the Wechsler Adult
      Intelligence Scale-Revised (WAIS-R) and the Barona regression equation. Results
      indicate that, while the PPVT-R is vulnerable to increasing levels of cognitive
      impairment among patients with fewer years of education, the PPVT-R is stable
      across mild to moderate levels of impairment for patients with greater than 12
      years of education. In a sub-sample of grossly cognitively intact patients (n =
      91), the PPVT-R standard score correlated significantly with estimated WAIS-R
      FSIQ (r =.61). Compared to the Barona equation, the PPVT-R was less likely to
      over-estimate WAIS-R FSIQ in the grossly cognitively intact patients. These data
      suggest the PPVT-R to be a useful estimate of premorbid ability for patients with
      a greater than high-school education.

PMID- 10916193
TI  - Prediction of functional status from neuropsychological tests in community
      dwelling elderly individuals.
AB  - Age-related dysfunction of frontal systems can result in deficits in planning,
      organization, self-control, and awareness of problems, which are likely to affect
      the ability to care for one's self. The purpose of this study was to determine
      the relationship between age-related frontal/executive deficits and impairment in
      instrumental activities of daily living (IADLs) in elderly individuals. Twenty
      seven community-dwelling individuals were administered a comprehensive battery of
      neuropsychological tests and a performance-based evaluation of IADLs. Multiple
      regression analyses indicated that executive function and depression severity
      accounted for a significant proportion of variance in IADLs, with executive
      function making the greatest contribution. Tests measuring other cognitive
      functions, such as memory, language, and spatial skills, did not contribute
      significantly to the prediction of functional status. Furthermore, executive
      measures accounted for more variance than other demographic characteristics such
      as general health status, age, and educational level. The results of this study
      indicate that executive dysfunction in normal aging may be the best predictor of
      functional decline. A better understanding of the mechanisms that underlie IADL
      skills will ultimately aid in the development of compensatory and intervention
      strategies designed to delay the onset of assisted living and nursing home
      placement.

PMID- 10916194
TI  - Fractioning the Hooper: a multiple-choice response format.
AB  - The Hooper Visual Organization Test (HVOT) provides an excellent illustration of
      the multifactorial nature of most neuropsychological tests. Although the HVOT
      clearly requires certain visual perceptual skills, the test also demands that the
      subject produce an overt verbal response - i.e., the name of the object that has
      been cut up and rearranged. Thus, individuals with disorders of confrontation
      naming may obtain low scores on the HVOT by virtue of their anomia, even if the
      primary perceptual skills that the HVOT purports to assess are intact. The
      present study was designed to minimize the demands of object naming on HVOT
      performance, by using a multiple choice format of the HVOT. Fourteen individuals
      with lateralized injury resulting from either cerebral vascular accident or
      cerebral contusion were administered the Boston Naming Test (BNT) and the
      standard version of the HVOT. Approximately 24 hours later, subjects were
      administered the Multiple-Choice Hooper Visual Organization Test (MC-HVOT). The
      MC-HVOT consisted of the 30 original HVOT stimuli presented with four response
      choices, including the correct response and three foils. A paired sample t test
      revealed that anomic subjects achieved a significantly greater number of correct
      responses on the MC-HVOT then under the standard HVOT administration. Subjects
      with both right and left hemisphere involvement benefited from diminished naming
      demands. Overall HVOT performance significantly improved when the object naming
      demand was reduced, resulting in a clearer assessment of visual integration
      skills. These findings may have significant implications for both interpretation
      of impairment and formulation of treatment recommendations.

PMID- 10916195
TI  - In response to the 1998 APA Division 40 Presidential Address: so where's the
      beef?
AB  - During the 1998 Division 40 presidential address by Linas Bieliauskas in San
      Francisco, several assertions were made contending that professional schools of
      psychology (PSP) had a deleterious effect on clinical neuropsychology by lowering
      professional standards, removing science from the curriculum, and producing
      mediocre clinicians. Bieliauskas reported to the author that he had based his
      opinion, in part, on data indicating that Boulder model graduates attained
      superior mean scores on the Examination for the Professional Practice in
      Psychology (EPPP) as compared to their Vail model counterparts. In order to
      determine whether significant differences existed between the two groups, a
      multivariate analysis of variance (MANOVA) was conducted using the 1997 EPPP
      scores reported by the Association of State and Provincial Psychology Boards
      (ASPPB, 1997). The author also provides a response to Bieliauskas' (1998)
      assertions.

PMID- 10916196
TI  - The quantified process approach: an emerging methodology to neuropsychological
      assessment.
AB  - An important development in the field of neuropsychological assessment is the
      quantification of the process by which individuals solve common
      neuropsychological tasks. The present article outlines the history leading to
      this development, the Quantified Process Approach, and suggests that this line of
      applied research bridges the gap between the clinical and statistical approaches
      to neuropsychological assessment. It is argued that the enterprise of quantifying
      the process approach proceeds via three major methodologies: (1) the "Satellite"
      Testing Paradigm: an approach by which new tasks are developed to complement
      existing tests so as to clarify a given test performance; (2) the Composition
      Paradigm: an approach by which data on a given test that have been largely
      overlooked are compiled and subsequently analyzed, resulting in new indices that
      are believed to reflect underlying constructs accounting for test performance;
      and (3) the Decomposition Paradigm: an approach which investigates the
      relationship between test items of a given measure according to underlying
      facets, resulting in the development of new subscores. The article illustrates
      each of the above paradigms, offers a critique of this new field according to
      prevailing professional standards for psychological measures, and provides
      suggestions for future research.

PMID- 10916197
TI  - Comparison of time and error rates on the trail making test among patients with
      head injuries, experimental malingerers, patients with suspect effort on testing,
      and normal controls.
AB  - Clinical utility of completion time and performance errors was investigated for
      the Trail Making Test (TMT; Reitan, 1958). Archival neuropsychological files for
      patients with mild and moderate/severe head injuries, as well as patients with
      suspect effort on neuropsychological testing, were examined and compared to
      controls and experimental malingerers. Time-to-completion scores differentiated
      the participants who were malingering and who gave suspect effort from those
      patients with head injuries. There were no differences in error rates among the
      head-injury groups or controls for either the TMT-A or TMT-B. Errors were also
      not uncommon among normal controls; 12% and 35% of the controls made at least one
      error on TMT-A and TMT-B, respectively. However, error rates for both the suspect
      effort and malingering groups were inflated on TMT-B as compared to the head
      injured and control groups. Results suggest that performance errors on the TMT
      lack diagnostic utility for persons with head injuries, and time-to-completion is
      still the best indicator of neuropathology. However, performance errors, in
      conjunction with inflated time scores on the TMT, may be useful in the assessment
      of malingering.

PMID- 10916198
TI  - Sex differences on the WMS-III: findings concerning verbal paired associates and
      faces.
AB  - Previous research suggests that women have better verbal learning than men,
      whereas there is little evidence of sex differences in nonverbal learning. The
      present study examined whether sex differences occur on subtests from the
      Wechsler Memory Scale-III (Wechsler, 1997). Verbal Paired Associates I & II (VPA)
      and Faces I & II were administered to 26 male and 26 female undergraduates. A
      measure of visual-spatial perception, the Judgment of Line Orientation Test,
      (JLO) was also administered. This was done to place the study within the context
      of an established literature concerning sex differences in cognition. To rule out
      potential confounds due to intelligence, WAIS-R FSIQs were estimated and used as
      covariates in statistical analyses. Women outperformed men on several VPA
      indices, with men scoring at the 25th percentile and women scoring at the 50th
      percentile. Although no differences were observed on Faces I & II, men
      outperformed women on JLO. Implications and recommendations concerning the
      clinical use of VPA are discussed.

PMID- 10916199
TI  - [Determinants of health and health policy. Part 3. From intervention of quality
      of life].
AB  - Effectiveness of outputs of a qualified intervention can be valued by several
      positive criteria corresponding to the "quality of life" conception, which is
      based on the feeling of the health and contentment. The finding that great
      differences in the income among different social groups in conditions of the
      liberal market society correlate with several health and social problems brought
      about to the hypothesis that the decrease of the differences in the income,
      accompanied by strengthening of various forms of the social cohesion, civic
      solidarity, legitimate equality, and ethical justice may substantially improve
      the health status of the population. The hypothesis has been verified in many
      epidemiological studies and found to be valid enough for the health policy and
      far-seeing economy. Analytics of the World Bank recommend to governments primary
      invest into the health of socially week groups in order to decrease their poverty
      and to keep social conciliation. World Health Organization (WHO) sets in its new
      program for Europe called "21 Goals for the 21st Century" that differences in the
      health status among the European states should diminish till 2020 by one third
      and within the countries by one quarter at least. Both goals should be achieved
      by a substantial improvement of the health status of the ill-adapted social
      groups and by significant improvement of those socioeconomical conditions which
      may have adverse effects namely on the differences in incomes, education and
      opportunities for employment.

PMID- 10916201
TI  - [Air pollution and sperm quality].
AB  - BACKGROUND: It has been described that an exposition of males to chemical
      substances may significantly impoverish quality and quantity of produced
      spermatozoa. The aim of our study was to test whether the polluted air in the
      Teplice district has negative effects on the quality of sperm of males living in
      this district. METHODS AND RESULTS: 325 males 18-year-old living in the Teplice
      district and in the control district of Prachatice were tested. Samples were
      taken in 1992 and 1994, always at the end of winter and in autumn. According to
      WHO laboratory manual for investigation of the human sperm, basic parameters were
      determined: volume of the semen, pH, motility, number and morphology of
      spermatozoa. In selected groups of males the frequency of aneuploidia of
      spermatozoa was also examined. Examination of aneuploidia was done using three
      color fluorescence in situ hybridisation with satellite DNA proves specific for
      X, Z and 8 chromosomes. Logistic regression was used for the data analysis and
      Odd's Ratio was estimated (OR's). OR's was found for the morphology of
      spermatozoa (4.1 and 10.1 for medium and high exposition respectively), for the
      head morphology (6.1 and 4.1) and in the percentage of motile spermatozoa (9.8
      and 3.5). More intensively exposed males had higher frequency of disomy in
      chromosomes X (p = 0.012), XY (p = 0.01), and Y (p < 0.001). CONCLUSIONS: Bio
      indicators of toxic and genetic impairment have shown lower quality of sperm in
      males in Teplice district.

PMID- 10916200
TI  - [Daily mortality and air pollution in the northern Czech Republic].
AB  - BACKGROUND: Several studies have demonstrated that the increase of air pollutants
      is related to the increase of the diurnal mortality. The aim of the work was to
      find correlation among the diurnal mortality and changes in the concentration of
      SO2, total suspended particles (TSP), and dust particles with aerodynamic
      diameter smaller than 10 microns (PM10) and smaller than 2.5 microns (PM2.5) in
      the external air of the North Bohemian brown-coal basin. METHODS AND RESULTS: All
      that died in 1982-1994 in coal-basin districts of the North Bohemia region were
      included into the data set. Method of long time series and the model of logistic
      regression were applied with correction to long-term trends, seasons, respiratory
      diseases and meteorological condition. Investigating the described relation
      regardless to age and sex, the increase of TSP by 100 micrograms/m3 was connected
      with significant increase of the total diurnal mortality by 3.4%. Significant
      differences between males and females were found. Meanwhile the mortality of
      males younger than 65 years increased, that of equally old females decreased.
      Contrary to it, in population of females older than 65 mortality increased and
      that males significantly decreased. CONCLUSION: Monitoring of the diurnal
      mortality and air pollution in relation to the sex reveals important for the
      identification of sensitive and vulnerable population subgroups. Illogic and
      difficult to explain is the decrease of mortality in conditions of increased air
      pollutants. Authors recommend repeating the analysis also in different
      epidemiological studies in order to distinguish whether the presented results are
      accidental or have a more general significance.

PMID- 10916202
TI  - [Maternal exposure to dust particles during pregnancy and fetal growth in 2
      regions with different levels of air pollution].
AB  - BACKGROUND: Recently, an association between adverse pregnancy outcome and air
      pollution was hypothesized in several papers. The aim of the present study is to
      evaluate the impact of particles with aerodynamic diameter < or = 10 microns
      (PM10) on the intrauterine growth retardation (IUGR) in two regions with the
      different levels of air pollution. METHODS AND RESULTS: The study group includes
      all singleton full term births of European origin over a two-year period in the
      district of Teplice (n = 1,943) and Prachatice (n = 883). Information on
      reproductive and health history and lifestyle was obtained from maternal
      questionnaires and medical records. IUGR was chosen as the indicator of
      reproductive effects. The mean concentration of PM10 for each women in particular
      gestational month was calculated. Three concentration intervals were constructed
      (low < 40 micrograms/m3; medium 40-50 micrograms/m3; high > or = 50
      micrograms/m3). Relative risk of IUGR was estimated for particular month and
      pollutant level. Influence of the potential confounders (maternal age, height and
      pre-pregnancy weight, smoking, season and the year of study) was controlled using
      logistic regression models; adjusted odd's ratio (AOR) was estimated. Relative
      risk of IUGR in Teplice District was increased for medium PM10 levels (AOR = 1.62
      CI: 1.07-2.46) (P < 0.02) as well as for high levels in the first gestational
      month (2.64 CI: 1.48-4.71) (P < 0.001). The same association was observed also in
      Prachatice District, though the PM10 did not achieve the "high" levels (> or = 50
      micrograms/m3). AOR for IUGR for mothers exposed in the 1st gestational month to
      medium PM10 levels was three times the risk of those exposed to low levels (3.50
      CI: 1.82-6.81) (P < 0.0003). No similar relationship was observed in any other
      gestational stage. CONCLUSIONS: Influence of particles or other associated air
      pollutants on fetal growth in early gestation is one of several possible
      explanations of these results. Timing of this effect in both different regions is
      compatible with a current hypothesis of IUGR etio-pathogenesis. Seasonal factors,
      one of the other possible explanations, is less probable. More investigation is
      required to evaluate a possible causal nature of the relationship observed.

PMID- 10916203
TI  - [Parameters of cellular immunity in maternal and umbilical cord blood in relation
      to air pollution. Preliminary results of a pregnancy outcomes study].
AB  - BACKGROUND: The study is a part of the project Pregnancy Outcome (Teplice
      Program) examining effects of polluted environment on the quality of reproduction
      in Teplice (high polluted) and Prachatice (control) districts. Selected
      parameters of cell mediated and humoral immunity in maternal and umbilical
      samples after delivery were assayed. METHODS AND RESULTS: Lymphocytes in 768
      samples of maternal venous blood and 739 samples of umbilical blood collected in
      May 1994-October 1997 were phenotyped using flow cytometry. Medical and personal
      questionnaires were used to obtain data on clinical risk factors during
      pregnancy, health and life style of mothers, the course and prolongation of
      labour and newborn's status. The percentages of T and NK lymphocytes in both
      umbilical and maternal blood were associated with a number of variables,
      including the course of labour. After adjustment for the other predictors, the
      percentage of NK lymphocytes was found significantly higher in Teplice than in
      Prachatice samples--in both maternal and umbilical blood. CONCLUSIONS: A part of
      the observed difference between distribution of NK and T lymphocytes can be
      attributed to living in the polluted district. To see effects of polluted
      environment, the association of seasonal difference in levels of major pollutants
      with seasonal changes in lymphocyte phenotype will be analyzed.

PMID- 10916204
TI  - [The program for detection and treatment of patients with familial
      hypercholesterolemia (MedPed FH) in the Czech Republic].
AB  - The authors present an international MedPed project (Make early diagnoses to
      prevent early deaths in medical pedigrees) the task of which is to increase the
      number of patients with familial lipid disorders identified and adequately
      treated all over the world. This will lead to significant decrease of premature
      deaths from coronary artery disease. Primary effort has been focused on familial
      hypercholesterolemia. The realization of MedPed program in Czech Republic is
      described.

PMID- 10916205
TI  - [Function and dysfunction of the endothelium].
AB  - Endothelium is a multi-functional barrier separating blood from interstitium. It
      plays a role in coagulation, inflammation, angiogenesis and it has vasomotor
      functions. The endothelial dysfunction can be considered as an initial stage of
      atherosclerosis. Using morphological and biochemical methods it is possible to
      study the influence of cardiovascular risk factors on the vessels and the effect
      of therapeutic interventions. A short review of endothelial functions,
      endothelial dysfunction and its quantification methods is presented in this
      article.

PMID- 10916206
TI  - [DNA diagnosis in Czech patients with tuberous sclerosis].
AB  - BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease
      characterised by mental retardation, epilepsy, facial angiofibromas, lesions in
      the CNS and the occurrence of hamartomata in different tissues. There are two
      genes responsible (TSC1 and TSC2). The aim of the study is to adopt a diagnosis
      of the disease on DNA level. METHODS AND RESULTS: 111 DNA samples were collected
      from 45 families with 54 clinically diagnosed patients. Three families with
      multiple incidence are linked to chromosome 9. In one case a large deletion was
      found using TSC2 specific cDNA probes. Most TSC mutations are supposed to be
      small mutations, identifiable by SSCP method. Using this method we examined all
      23 TSC1 exons and 20 out of 41 TSC2 exons. In the TSC1 gene we found 1 nonsense
      and 2 frameshift mutations and 2 intragenic polymorphisms useful for linkage. In
      the TSC2 exons was identified so far 6 aberrations, cause of which is being
      checked by sequencing. CONCLUSIONS: DNA mutation analysis is effective namely in
      families with multiple incidence. In such families the linkage can be used and
      there is more TSC1 cases which are easily identifiable. Analysis is not
      economical for differential diagnosis. Total number of revealed mutations (6.7%)
      matches last reports. No correlation between phenotype and type of mutation was
      found.

PMID- 10916208
TI  - [Effect of trypsinization on functional recovery of blast transformation of
      lymphocytes in adults and the aged].
AB  - BACKGROUND: During the physiological ageing, function of individual factors of
      the immune system tend to decline. The aim of our study was to compare the
      ability of lymphocytes to respond to polyclonal mitogens and to the stimulation
      by antibodies anti-CD2/CD2R after an previous trypsinization. METHODS: 17 adult
      (28 to 54-year-old) and 32 aged persons (63 to 90-year-old) were investigated.
      Lymphocytes were isolated from the peripheral blood, trypsinizated and
      subsequently incubated with polyklonic mitogens--phytohemaglutinin (PHA),
      concavalin (Con A), and a monoklonic antibody MoPr) anti-CD2/CD2R. The speed of
      recovery of the blastic transformation of trypsinizated lymphocytes was compared
      among the adult and aged persons. RESULTS: The stimulation values were in all
      studied time intervals significantly lower in aged persons then in adult ones (p
      < 0.001). In the group of aged persons, when the trypsinizated lymphocytes were
      stimulated by MoPr anti-CD2/CD2R, their ability of blastic transformation has not
      recovered to previous values. CONCLUSIONS: Our results indicate that function of
      T-lymphocytes diminishes in advanced age, however, lymphocytes still keep the
      ability to respond to specific stimulus. We found that the recovery of the
      blastic transformation of lymphocytes after a trypsinization requires in aged
      persons more than 20 hours. It probably corresponds with widespread decline of
      biological activities during ageing.

PMID- 10916207
TI  - [Prognostic factors and markers of activity in multiple myeloma (results of the
      Cooperative Group for Diagnosis and Treatment of Multiple Myeloma)].
AB  - BACKGROUND: Multiple myeloma (MM) is mostly fatal neoplastic disorder, however,
      the median survival of 30-40 months does not adequately express the wide spectrum
      courses of the disease. Therefore better prognostic factors are needed. METHODS
      AND RESULTS: We analyzed the value of both standard clinical features and
      cytokines for differential diagnosis, assessment of myeloma activity, prediction
      of overall survival and duration of remission in a group of 124 patients with MM
      and in 156 with various monoclonal gammapathies, respectively. The initial levels
      of Ca2+, LD, Hb, albumin, IL-6, PO4- and creatinine were useful for
      differentiation of monoclonal gammapathy of undetermined significance from MM.
      Serum IL-6 correlated with the stage and activity of MM, sIL-6R levels were
      significantly higher only in stage III and in newly diagnosed myeloma. We did not
      found the correlation between IL-6 and CRP levels. The usefulness of some
      standard features for prediction of survival was confirmed (Ca2+, Hb, clinical
      stage and subclassification A/B according to Durie-Salmon, SB2M > 4 mg/ml,
      creatinine, LD, ALP) as well as sIL-6R serum level determined both at time of
      diagnosis and during the course of disease. The prognosis of patients with
      reversible renal failure and those with intact renal function was not
      significantly different. Among other features, only serum sIL-6R, measured at
      time of diagnosis or during the course of disease, had significant predictive
      value for the assessment of duration of event-free survival in patients with MM.
      CONCLUSION: Due to short follow-up possible association of high levels of IFN
      gamma with better prognosis of MM could not be stated.

PMID- 10916209
TI  - [Problem situations between health personnel and patients (results of an analysis
      of patient complaints)].
AB  - Many problem situations arising between patients and medical officers have their
      source in the psyche of the persons involved. The aim of this study is to analyse
      psychological factors which may cone in these situations, and an attempt to
      describe, interpret and categorize them. We took as our starting point an
      analysis of protests submitted by patients (or their relatives) which were
      discussed by the management of the Faculty Hospital in Pilsen during the period
      of one year. We dealt with finished cases where the issue of the protest was of a
      psychological nature. Problem situations often arise under the influence of the
      following factors: personality features, the handling of information,
      maladaptation to a disease or situational factors. Majority of problem situations
      can be understood, prevented, and--if they arise--can be effectively handled. Pre
      graduation and continuous education in this areas should provide a significant
      aid.

PMID- 10916210
TI  - [History of the eradication of bovine brucellosis in the Czech Republic].
AB  - In the Czech republic, the program of recovery of the livestock from brucellosis
      caused by the micro-organisms Brucella abortus was successfully completed in
      1964. The campaign started in 1959 by the exploration of the complete cattle
      population by agglutination tests. Incidence of the disease was 211 positive
      cases for each 100 thousands, prevalence was 0.676% (20,481 animal in 654 foci of
      34 districts). The prevalence was significantly higher in large cattle units.
      Tens of new cases of the human brucellosis infections were reported. The process
      of sanitation was first based on the elimination of infected animals. In the
      later phase the more radical method was employed--the whole herds with infected
      individuals were eliminated and replaced. During the recovery program more than
      41 thousands of infected animals were eliminated. It required solving many
      complex methodological, legislative, organisational, economical and social
      problems. Serological test applied to more the half of the livestock population
      together with epizootiological, epidemiological and laboratory investigation
      helped to detect all foci. Eradication brought about substantial improvement of
      the productive and reproductive features of the cattle and eliminated the risks
      of infection with this zoonosis to the human population.

PMID- 10916211
TI  - [X-ray densitometry and ultrasonography of the heel bone--sensitivity and
      comparison with densitometry of the axial skeleton].
AB  - BACKGROUND: The aim of the study was to determine the relationship between dual
      energy x-ray absorptiometry (DXA) and quantitative ultrasonometry (QUS) of
      calcaneus and their correlation with axial bone mineral density. METHODS AND
      RESULTS: 1284 subjects were tested for BMD (Bone Mineral Density) by DXA at the
      spine and hip (707 subjects by DPX-L, Lunar, and 577 subjects by QDR-4500 A,
      Hologic) and calcaneus (by PIXI, Lunar). The calcaneus was also measured using
      the QUS (Achilles Plus, Lunar), on the same day. The mean age of the patients was
      56.5 +/- 11.6 years, mean height 166 cm, mean weight 70 kg. Three subjects were
      selected for precision error measurement with low, medium and high BMD of
      calcaneus (T-score of -2.2, -0.77 and 2.02, respectively) and scanned with re
      positioning at the right heel (PIXI and Achilles Plus) 21 times on one day for
      short term precision error and over 21 consecutive days for long term precision
      error. The in vivo short term precision error of the heel measurement (BMD, SOS,
      BUA) in subjects with normal BMD was 0.67%, 0.47% and 1.87%, respectively; the
      long term in vivo precision error was 1.14%, 0.26% and 2.95%, respectively. No
      significant difference was found between BMD values on the right and left heel. A
      statistically significant correlation (p < 0.001) was found between BUA and BMD
      (r = 0.71), SOS and BMD (r = 0.73), Stiffness and BMD (r = 0.77). The heel BMD
      was also significantly correlated to BMD of the femoral neck (r = 0.64) and BMD
      of total femur (r = 0.70) and BMD of lumbar spine (r = 0.59). CONCLUSIONS: The
      DXA of the heel underestimates the prevalence of osteoporosis. The results of the
      heel QUS (Stiffness) appear to be better correlated to femoral BMD than heel BMD.
      The observed correlation coefficient of 0.77 between QUS and DXA at the heel was
      statistically significant, but it explains only 60% of variability of the QUS of
      the heel.

PMID- 10916212
TI  - [Importance of reactivation of fosdrin-inhibited acetylcholinesterase in the
      brain and diaphragm for the in vivo therapeutic effect of oximes in rats poisoned
      with fosdrin].
AB  - BACKGROUND: The composition of the causal antidotal therapy of subjects, poisoned
      with organophosphorus insecticides, has not been satisfactorily solved till now
      in spite of the knowledge of the basic mechanism of action of these toxic
      substances. The purpose of this study is to evaluate which of currently used or
      perspective acetylcholinesterase reactivators seems to be the most efficacious to
      protect poisoned subjects. METHODS AND RESULTS: In experiments on white
      laboratory rats, the reactivating efficacy of selected acetylcholinesterase
      reactivators (oximes), administered at equimolar doses, was evaluated in target
      tissue of toxic effects of organophosphorus insecticides (diaphragm, brain) and
      compared with their therapeutic efficacy in the case of prophylactic
      administration with the help of the evaluation of mean efficacy dose of oximes,
      possible to protect rats exposed to supralethal dose of organophosphorus
      insecticide fosdrin for 24 hours. Our findings confirm that there are not
      statistically significant differences in reactivating and therapeutic efficacy of
      oximes tested against fosdrin in rats. CONCLUSIONS: The perspective
      acetylcholinesterase reactivators (H oximes) seem to be as suitable as currently
      used oximes for the therapy of acute poisonings with organophosphorus
      insecticides although they are not significantly more efficacious than currently
      used oximes as in the case of the treatment of poisoning with highly toxic
      organophosphorus compounds.

PMID- 10916214
TI  - [Cooperation between genetic counseling centers, cytogenetic laboratories and in
      vitro fertilization centers in the treatment of reproductive disorders].
AB  - The techniques of assisted reproduction have recently become the most effective
      methods of treatment of infertility; namely ICSI (intra-cytoplasmic sperm
      injection), MESA (microepididymal sperm aspiration), TESA (testicular sperm
      aspiration) and TESE (testicular sperm extraction). The techniques have been
      increasingly successful, even above the average efficiency of classical IVF (in
      vitro fertilization). It can be demonstrated by the percentage of ICSI-aided
      births percentage per 100% of embryotransfers in ISCARE; 1996 = 21.3%, 1997 =
      26.15%, 1998 = 29.7%. The successful use of these techniques is associated with
      the rise of risks which result from the selection of couples for assisted
      reproduction with genetic-based infertility and with the rise of risks involving
      the introduction of genetic-based defects in to the next generation. Presently, a
      list of indications is being developed, which, while still not accepted
      officially, identifies patients for genetic counselling. Only the counselling
      center has the competence to estimate genetic risks over generations.
      Subsequently, after selection by the center, during 1997 and 1998 the chromosomes
      of 731 patients were cytogenetically examined, representing 429 infertile couples
      from the centres ISCARE, PRONATAL, FERTIMED, and CAR 1. LF UK. Within these 429
      couples, belonging to four groups of indications, the cytogenetic examination was
      informative in 8.15%. This finding of a relatively high percentage (10 times more
      than in the general population) confirms the validity of the list of indications
      and the necessity of cooperation among the genetic counselling center,
      cytogenetic laboratory and the IVF centre.

PMID- 10916213
TI  - [Changes in left ventricular geometry in children and adolescents with primary
      hypertension].
AB  - BACKGROUND: Left ventricular hypertrophy is an independent risk factor of
      cardiovascular morbidity and mortality in adults. The results of 24-hour
      ambulatory blood pressure monitoring (ABPM) correlate better with signs of organ
      damage than values of casual blood pressure. The objective of this study was to
      investigate the relationships between the results of 24-hour ABPM and left
      ventricular geometry in school-aged children and adolescents with elevated blood
      pressure. METHODS AND RESULTS: 24-hour ABPM and echocardiographic assessment of
      left ventricle were performed in 108 children and adolescents age 8-20 years (77
      boys and 31 girls) with repeatedly elevated casual blood pressure (BP) values.
      Patients with secondary cause of hypertension were not included in this study.
      Based on ABPM results 57 patients out of total 108 had hypertension, the rest of
      51 subjects had their ambulatory BP values below 95. percentil and were labelled
      as white coat hypertensive (WCH). The left ventricular measurements in
      hypertensive subject were higher when compared with WCH (left ventricle posterior
      wall thickness 8.4 +/- 1.0 mm in hypertensive vs. 8.0 +/- 1.1 mm in WHC (p =
      0.047) and superscript left ventricular mass index 81.8 +/- 13.8 g/m2 vs 74.3 +/-
      12 g/m2 respectively; p = 0.003). No differences were found in anthropometric
      data including body mass index in both groups. There was a significant
      correlation between ambulatory BP and both left ventricle posterior wall
      thickness and left ventricular mass index. The strongest correlation was found
      between diurnal systolic ambulatory BP and left ventricle posterior wall
      thickness (r = 0.42; p < 0.001) as well as between 24-hour and diurnal systolic
      ambulatory BP and left ventricular mass index (both r = 0.47; p < 0.001).
      CONCLUSIONS: Both left ventricle posterior wall thickness a left ventricle mass
      index are higher in patients with hypertension documented by ABPM compared with
      WCH subjects. The strongest correlation was found between diurnal systolic
      ambulatory BP and both left ventricle posterior wall thickness and left
      ventricular mass index.

PMID- 10916215
TI  - [What is known today about the treatment of injuries of Charles IV in the year
      1350].
AB  - The author proceeds with his earlier 1990 contribution ou the complementary
      examination of the skull of the Czech king and Roman emperor Charles IV. Direct
      relationship between the injury to the cervical spine and the newly detected
      healed fractures of the mandible was established. A strong blow on the king's
      chin induced the four-fold dislocated fracture of the mandible. Based on our
      present knowledge of medieval medicine, and especially facial traumatology an
      attempt was made to clarify the treatment methods applied in management of the
      king's injury.

PMID- 10916216
TI  - [The optic nerve disk in open-angle glaucoma].

PMID- 10916217
TI  - [The retinal nerve fiber layer in glaucoma. II. The status of the nerve fiber
      layer and development of changes in the visual field. Prospective study].
AB  - PURPOSE: To determine whether retinal nerve fiber layer (RNFL) photographs can
      predict future glaucoma visual field damage. METHODS: In a prospective study 158
      red free photographs of the RNFL were made from November 1994 to June 1995. 28
      eyes of 19 patients with ocular hypertension (repeated intraocular pressure over
      21 mmHg and normal visual fields--Peristat 433 Rodenstock--at first examination)
      could be re-examined for an average time of 42.3 (SD 4.5) months. RESULTS: Only
      in one eye with normal RNFL at the first examination typical glaucoma visual
      field defects appeared (6%), but in 6 of 12 eyes (50%) with photographically
      demonstrable RNFL defects. The difference was statistically significant.
      CONCLUSION: There is only a minor probability, that visual field defects would
      appear during 3-5 years in eyes with normal RNFL photographs (6%), but about 50%
      of eyes with originally found RNFL defects.

PMID- 10916218
TI  - [The TNM classification system in malignant conjunctival neoplasms].
AB  - The authors submit a review of histological findings and classification according
      to the TNM-classification of conjunctival tumours in patients under dispensary
      care at the First Ophthalmological Clinic of the Faculty Hospital and Medical
      Clinic of the Comenius University in Bratislava during a 10-year period (1989
      1998). They included in the group 75 patients with clinically assessed
      conjunctival tumours (0.4% of the hospitalized patients). As to histological
      findings, 61 times (80.3%) a benign process was involved (naevus of the
      conjunctiva 12x) and 14x (19.7%) a malignant tumour, (7x times a primary
      malignant melanoma of the conjunctiva, 3x carcinoma). The authors recorded two
      relapses (one malignant melanoma of the conjunctiva, one melanoma penetrating
      into the orbit). The mean age of the patients was 47 years (from 1 to 82 years).
      In malignant melanoma of the conjunctiva stage T1 was detected in as many as 3/4
      of the patients (6 times), whereby stage pT1, 2 was found in 7 patients. In
      carcinoma the authors did not detect stage T1, only stage T2 in 2 patients, T3
      (pT3) in one patient.

PMID- 10916220
TI  - [Echographic findings in rhegmatogenous retinal detachment].
AB  - Echography of the bulbus is a useful examination method in eyes with a detached
      retina. It is essential in particular in eyes with opaque optic media, where the
      result of the ultrasonographic examination is frequently decisive for further
      therapeutic procedures. The echographic finding in rhegmatogenic detachment of
      the retina is usually quite typical and it is possible to assess relatively
      accurately the extent and shape of detachment. From echographic signs also the
      duration of detachment can be estimated. Ultrasound can also detect and locate a
      major retinal tear. A very effective method in the differential diagnosis of
      detachment of the retina is standardized echography of the bulbus.

PMID- 10916219
TI  - [The excimer laser and severe myopia--comparison of LASIK and PRK].
AB  - The aim of this study is to compare the results of photorefractive keratectomy
      (PRK) with method of laser-assisted keratomileusis (LASIK) in the treatment of
      high myopia by excimer laser. The study compares 100 eyes after PRK operated on
      by technique of multizonal ablation divided into group of moderately high myopia
      (-6.0 ... -9.0 Dsph/85 eyes) and severely high myopia (over -9.25 Dsph/15 eyes)
      with a group o 100 eyes operated on by LASIK similarly classified (moderately
      high myopia/67 eyes and severely high myopia/33 eyes). The eyes were treated by
      excimer laser Keracor 117 manufactured by Technolas company. Statistic analysis
      used one-way analysis of variance. One year after operation emmetropia within +/-
      1.0 Dsph was 52% in the first and 47% in the second group after PRK. After LASIK
      it was 71% and 54% respectively. No statistically significant differences have
      been found between the groups. In spite of this, analysis of postoperative
      complications, line loss of the preoperative best spectacle corrected acuity and
      patients satistaction shows that LASIK is a better method in correction of high
      myopia by excimer laser.

PMID- 10916221
TI  - [Methods in optic nerve disk digital planimetry].
AB  - The authors define the term planimetry in general and planimetry of the optic
      disc in particular and present a brief review of the history of planimetric
      evaluation of the optic disc. They describe a digital analyzer of their own
      design, the method of examination of the optic disc and further processing and
      recording of data. They define the indications and contraindications of
      examination, summarize the asset and limitations of the method used. The authors
      examined so far by digital planimetry 1575 optic discs of 856 patients.

PMID- 10916222
TI  - [Nonsteroidal anti-inflammatory agents after cataract surgery].
AB  - The authors present results of a prospective clinical study on efficacy of
      topical non-steroidal anti-inflammatory drugs (Naclof, CibaVision) in
      postoperative treatment. Fifty patients (50 eyes) after cataract extraction
      (phacoemulsification with intraocular lens implantation) were involved in this
      study. All patient underwent a thorough evaluation 1 week, 1 month and 4 months
      after operation. We have not seen any serious ocular complications. Results of
      this study indicate that non-steroidal anti-inflammatory drugs can be considered
      as a good alternative drug to steroids in patients after cataract operation.

PMID- 10916223
TI  - [Apoptosis and its importance in ophthalmology].

PMID- 10916224
TI  - [Methodologic principles in determination of the accommodation
      convergence/accommodation index, statistical measurements (literature review)].

PMID- 10916225
TI  - Comparable clinical outcomes of tubal embryo transfer for oligoastheno
      teratozoospermia treated with intracytoplasmic sperm injection and for female
      infertility treated with in vitro fertilization.
AB  - BACKGROUND: Female and male indications may each have their negative impacts on
      the success of assisted reproductive technologies. Reports regarding the outcomes
      of in vitro fertilization (IVF) vs. intracytoplasmic sperm injection (ICSI) are
      controversial. This study was conducted to investigate whether the clinical
      outcome of tubal embryo transfer (TET) for oligoastheno teratozoospermia treated
      with ICSI is different from that of tubal embryo transfer for female infertility
      treated with IVF. METHODS: From January 1997 to December 1998, results of tubal
      embryo transfers of 54 IVF (IVF-TET) cycles for female infertility were
      retrospectively compared with those of 49 ICSI (ICSI-TET) cycles for oligoastheno
      teratozoospermia. RESULTS: The fertilization rates were 78.1% +/- 21.8%, and
      78.0% +/- 21.9% for treatments with IVF-TET and ICSI-TET, respectively. The
      implantation rates were 13.8% and 21.2%, respectively. The pregnancy rates per
      transfer were 46.2% and 48.9%, and the abortion rates were 14.8% and 12.2% for
      treatments with IVF-TET and ICSI-TET, respectively. The above rates for the IVF
      TET and ICSI-TET groups were comparable. CONCLUSION: Male infertility due to
      oligoastheno teratozoospermia treated with ICSI-TET appears to have a comparable
      outcome to female infertility treated with IVF-TET.

PMID- 10916226
TI  - Seminal plasma zinc levels and sperm motion characteristics in infertile samples.
AB  - BACKGROUND: Zinc (Zn) in seminal plasma stabilizes the cell membrane and nuclear
      chromatin of spermatozoa. It may also have an antibacterial function. However,
      extremely high concentrations of Zn (10 to 100 x the normal range) may inhibit
      sperm motility and the function of the mannose receptor on the sperm head. In
      this study, we analyzed the correlation between Zn levels in seminal plasma and
      the characteristics of semen as measured by conventional and computer aided sperm
      analysis (CASA). METHODS: One hundred fifteen infertile couples were recruited
      for conventional semen analysis and CASA from December 1995 through January 1996,
      and Zn levels in semen samples were determined by flame atomic absorption
      spectroscopy (AAS). RESULTS: A good correlation in a positive direction (r =
      0.73, p = 0.0001) was noted between the total amount of Zn per ejaculate and the
      Zn concentration. The Zn concentration in seminal plasma was negatively
      correlated with the seminal pH (r = -0.35, p = 0.0081). There was no significant
      correlation between the total amount of Zn per ejaculate and sperm
      characteristics, including sperm count, motility (% sperm count), progressive
      motility (% motility), rapid motility (% motility), average path velocity (VAP,
      microns/s), straight-line velocity (VSL, microns/s), curvilinear velocity (VCL,
      microns/s), amplitude of lateral head displacement (ALH, microns), beat/cross
      frequency (BCF, beats/s), straightness (STR), and linearity (LIN). There was also
      no significant correlation between the Zn concentration in seminal plasma and the
      above sperm characteristics. CONCLUSION: The characteristics of semen as
      determined by conventional semen analysis or CASA bore no correlation with total
      seminal Zn amount or Zn concentrations in the ejaculates. Routine determination
      of the Zn concentration in seminal plasma offers no advantages in infertility
      work-ups.

PMID- 10916227
TI  - Comparison of sexual behaviors between male homosexuals and male heterosexuals in
      Taiwan.
AB  - BACKGROUND: Homosexuality and sexual behavior have attracted great attention in
      the acquired immunodeficiency syndrome (AIDS) epidemic. This study primarily
      explores the risky behaviors and patterns of sexual behavior of male homosexuals
      in Taiwan. METHODS: Comparison study methodology was adopted. Ninety-two male
      homosexuals, as the study group, were recruited from gay bars and gay
      organizations, and 91 male heterosexuals, with similar ages and educational
      levels, were recruited as a control group for comparison. Semi-structured
      interviews were carried out and anonymous questionnaires were self-administered.
      RESULTS: (1) The mean age at the time of first sexual intercourse of the study
      group was younger than that of the control group. (2) The rate of having two or
      more sexual partners in the study group was significantly higher. (3) However,
      the rate of condom use during recent intercourse was higher in the control group
      than in the study group. (4) Sexual knowledge and attitudes toward sexuality in
      the study group were more open, but their sexual desires, as rated by the
      questionnaire, were more suppressed than those of the control group. (5) In terms
      of courtship, the study group was less constrained by the social values of
      marriage and tended to separate sex from love. CONCLUSION: Similar to western
      studies, our study found that the study group in Taiwan adopted more risky sexual
      behaviors. Each group had its particular sexual behavioral pattern and subculture
      of sexuality. However, a longitudinal follow-up study with ethnographic
      perspective is necessary for a more sophisticated understanding of the trends and
      changes of sexual behavior in homosexuals.

PMID- 10916228
TI  - An epidemiologic study of dog bites among postmen in central Taiwan.
AB  - BACKGROUND: The purpose of this study was to investigate the occupational hazard
      of dog bites among postmen. METHODS: Data were collected from postmen working for
      9 post offices in central Taiwan using the postmen's 1994 annual health
      examinations. Of 237 eligible postmen, 192 postmen (81.0%), including 183 men and
      9 women, participated in this study. Detailed personal and occupational
      information and experiences of dog bites during a 3-year period (1991 to 1994)
      were obtained through a structured questionnaire. Baseline variables and
      occupational data were examined as risk factors for the dog bites among the
      postmen using multiple logistic regression analysis. RESULTS: We found that,
      during the 3-year period of study, 71.4% (137/192) of the postmen had had the
      experience of dog bites. Only 48.9% (67/137) had sought medical attention after a
      dog bite injury. There was also a regional difference among postmen experiencing
      dog bites. After controlling multiple variables, there was a 2.70-fold increase
      in risk of having dog bite accidents among postmen who worked in rural areas
      compared with those who worked in urban areas (95% confidence interval, 1.39 to
      5.25). CONCLUSION: Dog bites are a common occupational hazard for postmen. The
      incidence of dog bites among postmen is higher than the reported rates among
      general populations. There is a need to develop an effective prevention strategy
      to reduce the occurrence of dog bites among postmen. We also emphasize the
      importance of seeking adequate medical treatment after a dog bite injury.

PMID- 10916229
TI  - Adult intussusception: a 12-year experience, with emphasis on etiology and
      analysis of risk factors.
AB  - BACKGROUND: To determine the incidence, causes, and associated risk factors of
      adult intussusception. METHODS: Forty-five cases of adult intussusception proven
      by surgery were collected from 58,000 surgeries performed from December 1986
      through December 1998. The condition leading to intussusception, imaging studies,
      and clinical risk factors were analyzed. RESULTS: Nineteen men and 26 women, 18
      to 83 years of age (mean, 52.6 years), experienced intussusception. The incidence
      of adult intussusception was 0.08% of abdominal surgeries and 3.0% of intestinal
      obstructions. A benign process was diagnosed in 25 cases (55.6%), malignancy in
      16 cases (35.6%), surgery-related intussusception in 1 case (2.2%), and an
      idiopathic condition existed in 3 cases (6.6%). The major cause of adult
      intussusception due to benign lesions was polyps (12/25) and for malignancy, it
      was colonic adenocarcinoma (14/16). The diagnostic imaging rates were 52% for
      computed tomography, 41% for barium studies and 32% for abdominal ultrasound.
      There was no mortality due to intussusception; 4 patients (8.9%) died of colon
      cancer with liver metastasis. No definite risk factor was identified, but
      leukocytosis and a shorter preoperative duration tended to increase the risk of
      complications (p = 0.084, 0.082 respectively). CONCLUSION: Malignancy was the
      major cause of colonic intussusception, as was a benign process the primary cause
      of intestinal intussusception. These adult patients with intussusception received
      adequate surgical care and had a good prognosis except for those with colon
      cancer and liver metastasis.

PMID- 10916230
TI  - Villous adenomas of the urinary tract: report of two cases.
AB  - Villous adenomas are rare tumors of the urinary tract. They are morphologically
      identical to their counterpart in the colon. The histogenesis and malignant
      potential are uncertain. We report on 2 cases, 1 each in the urethra and bladder.
      The first is a 57-year-old male who complained of an acute attack of urinary
      retention. A papillary tumor, measuring 3.0 x 2.0 cm, was found in the prostatic
      portion of the urethra by cystoscopy, and the tumor was removed transurethrally.
      The second case, a 33-year-old male, was a victim of chronic pyelonephritis with
      severe hydronephrosis resulting from a left renal staghorn stone. A papillary
      tumor was noted on the dome of the urinary bladder. The tumor, measuring 2.0 x
      2.0 cm, was resected by transurethral resection. No recurrence or malignant
      transformation has been found during the follow-up period. The features of
      morphology, immunohistochemistry, and histochemistry were well studied. Staining
      by periodic acid-Schiff (PAS) stain, Alcian blue at pH 1.0, and Alcian blue at pH
      2.5 were all positive. The carcinoembryonic antigen was strongly positive in the
      neoplastic glands, especially in the luminal border. We also review the previous
      literature and discuss the histogenesis, diagnosis, and treatment.

PMID- 10916231
TI  - Extensive dissection to the right sinus of Valsalva in coronary angioplasty: case
      report.
AB  - Percutaneous transluminal coronary angioplasty was first introduced in 1977 by
      Gruentzig and now provides the option of nonsurgical revascularization for up to
      1/2 of patients who undergo diagnostic catheterization for coronary artery
      disease. Today, although there have been great improvements in technology and
      operator experience, complications still occur during coronary angiography and
      revascularization. Coronary dissection, one of the most frequently occurring
      complications during angiography and angioplasty, occurs in various forms.
      However, right coronary dissection and retrograde extension to the aortic sinus
      of Valsalva is extremely unusual during an interventional procedure. We report
      such an unusual complication which occurred during balloon angioplasty and which
      was successfully managed by coronary stenting. This unusual complication may have
      potential risk of quickly involving the entire aorta, causing acute severe aortic
      regurgitation, acute myocardial infarction, requiring emergency surgery, and even
      resulting in death. Therefore, prompt diagnosis and management of this
      complication are very important.

PMID- 10916232
TI  - Septo-optic dysplasia with unilateral optic nerve hypoplasia: case report.
AB  - Septo-optic dysplasia (de Morsier syndrome) is a well-described entity that
      includes optic nerve hypoplasia and the absence of the septum pellucidum with or
      without pituitary abnormalities. We describe a case with unilateral optic nerve
      hypoplasia and absence of a septum pellucidum. A 6-year-old boy was referred to
      our clinic because of poor visual acuity. His best-corrected visual acuity was
      counting fingers at 15 cm in the right eye and 1.0 in the left eye. Extraocular
      muscle movements were normal, and exotropia of 30 prism diopters by Hirschberg
      test in the right eye was present. The pupils were equal and reactive to light
      with a mild Marcus Gunn pupillary response in the right eye. Perimetry revealed
      small visual fields in the superior quadrants of the right eye, while the left
      eye was normal. Ophthalmoscopic examination showed a small pale optic disc in the
      right eye; the optic disc of the left eye was normal. Magnetic resonance imaging
      showed the absence of the septum pellucidum. Endocrine studies revealed no
      evidence of pituitary insufficiency.

PMID- 10916233
TI  - Hemorrhagic disease in a newborn due to inadequate vitamin K prophylaxis: case
      report.
AB  - Vitamin K prophylaxis for all neonates has been recommended to prevent
      hemorrhagic disease of the newborn (HDN), but it is still an uncommon practice in
      most developing countries throughout the world. In the United States and Canada,
      where vitamin K injections continue to be recommended in the newborn period, HDN
      is not a major concern. The risk factors for HDN include inadequate vitamin K
      prophylaxis, exclusively breast-fed infants, diarrhea, and alternative causes of
      vitamin K deficiency, such as liver disease and cystic fibrosis. We present an
      exclusively breast-fed 3-week-old infant with diarrhea for 2 days who died from
      intracranial hemorrhage related to HDN despite having received a single
      intramuscular injection of 0.2 mg of vitamin K at birth. Hemorrhage in the infant
      from vitamin K deficiency should be a concern for pediatricians and
      obstetricians. We emphasize the importance of administering an adequate dosage of
      vitamin K for prevention of HDN, particularly in an exclusively breast-fed
      infant.

PMID- 10916234
TI  - Unusual presentation of pulmonary coccidioidomycosis in a traveler.

PMID- 10916235
TI  - Technology-based delivery of PBL curricular elements at JABSOM.

PMID- 10916236
TI  - Chronic venous ulcers.

PMID- 10916237
TI  - Primary venous disease: superficial incompetence. Saving the saphenous vein.

PMID- 10916238
TI  - Ambulatory venous surgery versus sclerotherapy.

PMID- 10916239
TI  - New trends and operative techniques in the management of varicose veins.

PMID- 10916240
TI  - Case of superficial incompetence.

PMID- 10916241
TI  - Perforator incompetence. Case of perforator incompetence--making SEPS better.

PMID- 10916242
TI  - The venous ulcer.

PMID- 10916243
TI  - Ultrasound guided sclerotherapy (USGS) for perforating veins (PV).

PMID- 10916244
TI  - Case of perforator incompetence.

PMID- 10916246
TI  - The role of angioscopic valve repair for primary valve incompetence (PVI).

PMID- 10916245
TI  - Primary venous disease: deep and superficial reflux. Treatment of primary venous
      insufficiency.

PMID- 10916247
TI  - Internal valvuloplasty.

PMID- 10916248
TI  - Case of primary deep venous reflux.

PMID- 10916249
TI  - Post-thrombotic disease: deep and superficial. Case of secondary deep venous
      disease-something can always be done.

PMID- 10916250
TI  - Case of secondary deep venous disease--valve transplantation.

PMID- 10916251
TI  - Angioplasty and stenting of the obstructed iliac vein.

PMID- 10916252
TI  - Case of secondary deep venous disease.

PMID- 10916253
TI  - Acoustical properties of speech as indicators of depression and suicidal risk.
AB  - Acoustic properties of speech have previously been identified as possible cues to
      depression, and there is evidence that certain vocal parameters may be used
      further to objectively discriminate between depressed and suicidal speech.
      Studies were performed to analyze and compare the speech acoustics of separate
      male and female samples comprised of normal individuals and individuals carrying
      diagnoses of depression and high-risk, near-term suicidality. The female sample
      consisted of ten control subjects, 17 dysthymic patients, and 21 major depressed
      patients. The male sample contained 24 control subjects, 21 major depressed
      patients, and 22 high-risk suicidal patients. Acoustic analyses of voice
      fundamental frequency (Fo), amplitude modulation (AM), formants, and power
      distribution were performed on speech samples extracted from audio recordings
      collected from the sample members. Multivariate feature and discriminant analyses
      were performed on feature vectors representing the members of the control and
      disordered classes. Features derived from the formant and power spectral density
      measurements were found to be the best discriminators of class membership in both
      the male and female studies. AM features emerged as strong class discriminators
      of the male classes. Features describing Fo were generally ineffective
      discriminators in both studies. The results support theories that identify
      psychomotor disturbances as central elements in depression and suicidality.

PMID- 10916254
TI  - Clustering ECG complexes using hermite functions and self-organizing maps.
AB  - An integrated method for clustering of QRS complexes is presented which includes
      basis function representation and self-organizing neural networks (NN's). Each
      QRS complex is decomposed into Hermite basis functions and the resulting
      coefficients and width parameter are used to represent the complex. By means of
      this representation, unsupervised self-organizing NN's are employed to cluster
      the data into 25 groups. Using the MIT-BIH arrhythmia database, the resulting
      clusters are found to exhibit a very low degree of misclassification (1.5%). The
      integrated method outperforms, on the MIT-BIH database, both a published
      supervised learning method as well as a conventional template cross-correlation
      clustering method.

PMID- 10916255
TI  - Wavelet compression of ECG signals by the set partitioning in hierarchical trees
      algorithm.
AB  - A wavelet electrocardiogram (ECG) data codec based on the set partitioning in
      hierarchical trees (SPIHT) compression algorithm is proposed in this paper. The
      SPIHT algorithm [1] has achieved notable success in still image coding. We
      modified the algorithm for the one-dimensional case and applied it to compression
      of ECG data. Experiments on selected records from the MIT-BIH arrhythmia database
      revealed that the proposed codec is significantly more efficient in compression
      and in computation than previously proposed ECG compression schemes. The coder
      also attains exact bit rate control and generates a bit stream progressive in
      quality or rate.

PMID- 10916256
TI  - Methods for robust clustering of epileptic EEG spikes.
AB  - We investigate algorithms for clustering of epileptic electroencephalogram (EEG)
      spikes. Such a method is useful prior to averaging and inverse computations since
      the spikes of a patient often belong to a few distinct classes. Data sets often
      contain outliers, which makes algorithms with robust performance desirable. We
      compare the fuzzy C-means (FCM) algorithm and a graph-theoretic algorithm. We
      give criteria for determination of the correct level of outlier contamination.
      The performance is then studied by aid of simulations, which show good results
      for a range of circumstances, for both algorithms. The graph-theoretic method
      gave better results than FCM for simulated signals. Also, when evaluating the
      methods on seven real-life data sets, the graph-theoretic method was the better
      method, in terms of closeness to the manual assessment by a neurophysiologist.
      However, there was some discrepancy between manual and automatic clustering and
      we suggest as an alternative method a human choice among a limited set of
      automatically obtained clusterings. Furthermore, we evaluate geometrically
      weighted feature extraction and conclude that it is useful as a supplementary
      dimension for clustering.

PMID- 10916257
TI  - Conversion of magnetocardiographic recordings between two different multichannel
      SQUID devices.
AB  - Comparison of biomagnetic measurements performed with different multichannel
      magnetometers is difficult, because differing sensor types and locations do not
      allow measurements from the same locations in respect to the body. In this study,
      two transformation procedures were utilized to compare magnetocardiograms (MCG)
      recorded with two different multisensor systems. Signals from one sensor array
      were used to compute parameters of a multipole expansion or minimum-norm
      estimates at 1-ms steps over the cardiac cycle. The signals of the second sensor
      array were then simulated from the computed estimates and compared against
      measured data. Both the multipole- and the minimum-norm-based transformation
      method yielded good results; the average correlation between simulated and
      measured signals was 93%. Thus, the methods are useful to compare MCG recordings
      performed using differing sensor configurations, e.g., for multicenter patient
      studies. This study provides the first empirical basis for assessing the
      transformation of MCG data of differing devices by general model-based field
      reconstructions.

PMID- 10916258
TI  - Enhancement of bowel sounds by wavelet-based filtering.
AB  - This paper evaluates the performance of an automatic method for structural
      decomposition, noise removal and enhancement of bowel sounds (BS), based on the
      wavelet transform. The proposed method combines multiresolution analysis with
      hard thresholding to compose a wavelet transform-based stationary-nonstationary
      (WTST-NST) filter, for enhanced separation of bowel sounds (BS) from superimposed
      noise. Quantitative and qualitative analysis of the experimental results, when
      applying the WTST-NST filter to BS recorded from controls and patients with
      gastrointestinal dysfunction, prove that the ability of the WTST-NST filter to
      remove noise and reveal the authentic structure of BS is excellent. By
      eliminating the need to record a noise reference signal, this method reduces
      hardware overhead when analysis of BS is the primary aim. The method is
      independent of subjective human judgement for selection of noise reference
      templates, is robust to different levels of signal interference, and, due to its
      simplicity, can easily be used in clinical medicine.

PMID- 10916259
TI  - A telemetry system for the study of spontaneous cardiac arrhythmias.
AB  - The characteristics of spontaneous cardiac arrhythmias leading to sudden cardiac
      death are largely unknown. To study arrhythmias in animal models, an eight
      channel implantable radio telemetry system has been developed to record
      continuously cardiac electrograms over a period of weeks to months, with
      maintenance restricted to changing batteries. The inputs are connected in a
      unipolar manner. Each channel has a gain of fifty and is AC coupled, band limited
      to 0.07-260 Hz. The signals are digitized with 12 bits resolution at 1000
      samples/s. The amplifiers, analog-to-digital converter, and control logic are
      packaged in an implantable unit. An umbilical cable is passed through the skin to
      an external backpack unit for power and data transmission. A custom serial
      interface card, a PC/104 form factor 25-MHz 80386-based single-board computer
      with a PCMCIA wireless local area network (WLAN) card, and battery power supply
      make up the backpack. Data are read into the parallel port of the computer,
      buffered, then transmitted over the WLAN to the laboratory network where it can
      be analyzed and archived. Approximately 12 h of 14,000 bytes/s data can be
      collected with each set of batteries. The system is suitable for continuous
      monitoring of animal models of spontaneous arrhythmias and sudden cardiac death.

PMID- 10916260
TI  - A simulation study evaluating the performance of high-density electrode arrays on
      myocardial tissue.
AB  - Multielectrode arrays used to detect cellular activation have become so dense
      (electrodes per square millimeter) as to jeopardize the basic assumptions of
      activation mapping; namely, that electrodes are points adequately separated as to
      not interfere with the tissue or each other. This paper directly tests these
      assumptions for high-density electrode arrays. Using a finite element model with
      modified Fitzhugh-Nagumo kinetics, we represent electrodes as isopotential
      surfaces of varying widths and spacing ratio (SR) (center-to-center spacing
      divided by electrode width). We examine the signal strength and ability of a
      single electrode to detect activation due to a passing wavefront. We find that
      high-density arrays do not cause significant wavefront curvature or alter
      activation timing in the underlying tissue. Relationships between signal
      strength, cross talk, and array design are explained by the interaction of the
      propagating wavefront and induced sources on the isopotential electrodes.
      Sensitivity analysis shows that these results may be generalized to a wide range
      of physiologically relevant designs and applications. We conclude that electrode
      array designs in which electrode spacing greatly exceeds electrode diameter are
      overly conservative and that arrays with a SR of less than 2.0 may perform
      successfully in electrophysiological studies.

PMID- 10916261
TI  - Analysis of position and isometric joysticks for powered wheelchair driving.
AB  - The control interface is one of the most critical components of the electric
      powered wheelchair (EPW). The control interface must accommodate the user's
      limitations and maximize the user's abilities. This study extended Fitts' Law for
      target-acquisition to a continuously updated target. The extended Fitts' Law was
      used to examine EPW driving with a standard position sensing joystick and a
      prototype isometric joystick (IJ). The extended Fitts' Law provides insight into
      the difficulty of performing target-acquisition tasks with an EPW. The test
      results showed significant differences (p < 0.05) among the two types of
      joysticks for selected measures of information processing capacity, movement
      time, root-mean-square-error, and average velocity while performing turning
      maneuvers. The mean values indicate that the IJ may provide superior turning
      performance.

PMID- 10916262
TI  - Chronic neural stimulation with thin-film, iridium oxide electrodes.
AB  - Experiments were conducted to assess the effect of chronic stimulation on the
      electrical properties of the electrode-tissue system, as measured using
      electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV).
      Silicon, micromachined probes with multiple iridium oxide stimulating electrodes
      (400-1600 micron 2) were implanted in guinea pig cortex. A 10-17 day post
      operative recovery period was followed by five days of monopolar stimulation, two
      hours/electrode each day using biphasic, constant current stimulation (5-100
      microA, 100 microseconds/phase). EIS and CV data were taken before and after
      stimulation. The post-stimulation impedance [at mid-range frequencies (100 Hz-100
      kHz)] consistently and significantly decreased relative to prestimulation levels.
      Impedance magnitude increased permanently at low frequencies (< 100 Hz),
      correlating to a change in the charge storage capacity (the area under a cyclic
      voltammagram). Impedance magnitude significantly increased during the recovery
      period, though this increase could be mostly reversed by applying small currents.
      A mathematical model of the electrode-tissue system impedance was used to analyze
      in vivo behavior. The data and modeling results shows that applying charge to the
      electrode can consistently reduce the impedance of the electrode-tissue system.
      Analysis of explanted probes suggests that the interaction between the tissue and
      electrode is dependent on whether chronic pulses were applied. It is hypothesized
      that the interface between the tissue and metal is altered by current pulsing,
      resulting in a temporary impedance shift.

PMID- 10916263
TI  - Closed-loop stimulation of hypoglossal nerve in a dog model of upper airway
      obstruction.
AB  - Electrical stimulation of upper airway (UAW) muscles has been under investigation
      as a treatment method for obstructive sleep apnea (OSA). Particular attention has
      been given to the electrical activation of the genioglossal muscle, either
      directly or via the stimulation of the hypoglossal nerve (HG), since the
      genioglossus is the main tongue protrusor muscle. Regardless of the stimulation
      site or method, an implantable electrical stimulation device for OSA patients
      will require a reliable method for detection of obstructive breaths to apply the
      stimulation when needed. In this paper, we test the hypothesis that the activity
      of the HG nerve can be used as a feedback signal for closed-loop stimulation of
      the HG nerve in an animal model of UAW obstruction where a force is applied on
      the submental region to physically narrow the airways. As an advantage, the
      method uses a single electrode for both recording and stimulation of the HG
      nerve. Simple linear filtering techniques were found to be adequate for producing
      the trigger signal for the electrical stimulation from the HG recordings.
      Esophageal pressure, which was used to estimate the size of the UAW passage,
      returned to the preloading values during closed-loop stimulation of the HG nerve.
      The data demonstrate the feasibility of the closed-loop stimulation of the HG
      nerve using its activity as the feedback signal.

PMID- 10916264
TI  - Femoral surface strain in intact composite femurs: a custom computer analysis of
      the photoelastic coating technique.
AB  - Understanding how forces are distributed through the proximal femur has many
      clinical applications for surgeons, researchers, and prosthetic designers. A new
      system for two-dimensional analysis of femoral surface strain was developed and
      applied to intact composite femurs. The photoelastic coating method was used to
      resolve the surface strain under axial loading, and strain analysis was performed
      using digital imaging of the strain patterns and original computer programs. The
      technique provides qualitative and quantitative data that describes overall
      femoral surface strains more completely than previous point analysis and strain
      gauge techniques. Results from repeated testing found the photoelastic process,
      computer imaging and computer analysis of strain areas to be statistically
      repeatable.

PMID- 10916265
TI  - Staging of cervical cancer with soft computing.
AB  - This paper describes a way of designing a hybrid decision support system in soft
      computing paradigm for detecting the different stages of cervical cancer.
      Hybridization includes the evolution of knowledge-based subnetwork modules with
      genetic algorithms (GA's) using rough set theory and the Interactive Dichotomizer
      3 (ID3) algorithm. Crude subnetworks obtained via rough set theory and the ID3
      algorithm are evolved using GA's. The evolution uses a restricted mutation
      operator which utilizes the knowledge of the modular structure, already
      generated, for faster convergence. The GA tunes the network weights and structure
      simultaneously. The aforesaid integration enhances the performance in terms of
      classification score, network size and training time, as compared to the
      conventional multilayer perceptron. This methodology also helps in imposing a
      structure on the weights, which results in a network more suitable for extraction
      of logical rules and human interpretation of the inferencing procedure.

PMID- 10916266
TI  - Detection of leukocytes in contact with the vessel wall from in vivo microscope
      recordings using a neural network.
AB  - Leukocytes play an important role in the host defense as they may travel from the
      blood stream into the tissue in reacting to inflammatory stimuli. The leukocyte
      vessel wall interactions are studied in post capillary vessels by intravital
      video microscopy during in vivo animal experiments. Sequences of video images are
      obtained and digitized with a frame grabber. A method for automatic detection and
      characterization of leukocytes in the video images is developed. Individual
      leukocytes are detected using a neural network that is trained with synthetic
      leukocyte images generated using a novel stochastic model. This model makes it
      feasible to generate images of leukocytes with different shapes and sizes under
      various lighting conditions. Experiments indicate that neural networks trained
      with the synthetic leukocyte images perform better than networks trained with
      images of manually detected leukocytes. The best performing neural network
      trained with synthetic leukocyte images resulted in an 18% larger area under the
      ROC curve than the best performing neural network trained with manually detected
      leukocytes.

PMID- 10916267
TI  - Receiver operating characteristic analysis for intelligent medical systems--a new
      approach for finding confidence intervals.
AB  - Intelligent systems are increasingly being deployed in medicine and healthcare,
      but there is a need for a robust and objective methodology for evaluating such
      systems. Potentially, receiver operating characteristic (ROC) analysis could form
      a basis for the objective evaluation of intelligent medical systems. However, it
      has several weaknesses when applied to the types of data used to evaluate
      intelligent medical systems. First, small data sets are often used, which are
      unsatisfactory with existing methods. Second, many existing ROC methods use
      parametric assumptions which may not always be valid for the test cases selected.
      Third, system evaluations are often more concerned with particular, clinically
      meaningful, points on the curve, rather than on global indexes such as the more
      commonly used area under the curve. A novel, robust and accurate method is
      proposed, derived from first principles, which calculates the probability density
      function (pdf) for each point on a ROC curve for any given sample size.
      Confidence intervals are produced as contours on the pdf. The theoretical work
      has been validated by Monte Carlo simulations. It has also been applied to two
      real-world examples of ROC analysis, taken from the literature (classification of
      mammograms and differential diagnosis of pancreatic diseases), to investigate the
      confidence surfaces produced for real cases, and to illustrate how analysis of
      system performance can be enhanced. We illustrate the impact of sample size on
      system performance from analysis of ROC pdf's and 95% confidence boundaries. This
      work establishes an important new method for generating pdf's, and provides an
      accurate and robust method of producing confidence intervals for ROC curves for
      the small sample sizes typical of intelligent medical systems. It is conjectured
      that, potentially, the method could be extended to determine risks associated
      with the deployment of intelligent medical systems in clinical practice.

PMID- 10916268
TI  - Electric potential produced by a dipole in a homogeneous conducting sphere.
AB  - The potential produced by a dipole in a homogeneous conducting sphere is useful
      in simulation study, and the current available solutions still suffer from some
      shortcomings. In this communication, a closed solution is developed for the
      precise calculation of the potential anywhere in the spherical model.

PMID- 10916269
TI  - Wavelet time entropy, T wave morphology and myocardial ischemia.
AB  - Using wavelets, we computed the entropy of the signal at various frequency levels
      (wavelet time entropy) and, thus, find an optimal measure to differentiate normal
      states from ischemic ones. This new indicator is independent from the ST segment
      and yet provide a conclusive detection of the ischemic states.

PMID- 10916270
TI  - Bayesian analysis of blood glucose time series from diabetes home monitoring.
AB  - This paper describes the application of a novel Bayesian estimation technique to
      extract the structural components, i.e., trend and daily patterns, from blood
      glucose level time series coming from home monitoring of insulin dependent
      diabetes mellitus patients. The problem is formulated through a set of stochastic
      equations, and is solved in a Bayesian framework by using a Markov chain Monte
      Carlo technique. The potential of the method is illustrated by analyzing data
      coming from the home monitoring of a 14-year old male patient.

PMID- 10916271
TI  - HIV and tuberculosis.

PMID- 10916272
TI  - Adrenocortical reserve and morphology in tuberculosis.
AB  - Ninety seven patients (63 males, mean age 31.8 years, SD 2.3) with various forms
      of tuberculosis were studied. All of them were HIV negative. Thirty normal
      control subjects (16 males, mean age 36.4 years, SD 1.8) were also studied. Fifty
      eight of the 97 patients (59.8%) were malnourished (BMI < 18 kg/m2). The mean
      basal serum cortisol was lower in the TB group (n = 91) (351 nmol/1; SD 150) as
      compared to the normal control group (n = 8) (402 nmol/1; SD 93) but this
      difference did not attain statistical significance. Following administration of
      synthetic ACTH (cosyntropin), the 30 and 60 minutes mean serum cortisol values in
      the TB group were significantly lower as compared to the normal control group (p
      < 0.05). Forty five of the 91 patients (49.5%) who underwent the ACTH stimulation
      test had compromised adrenal reserve. Fourteen of the 86 patients (16.3%) in whom
      adrenal morphology was studied revealed adrenal gland enlargement on abdominal CT
      scan. ACTH stimulation was done in 12 of these 14 patients and eight of them had
      compromised adrenal reserve. Repeat ACTH stimulation done six months to one year
      after treatment in 13 patients revealed significantly increased 30 minutes (p <
      0.05) and 60 minutes (p < 0.05) serum cortisol values. While nine of these 13
      patients were negative responders before treatment, only three of them had
      evidence of compromised adrenal reserve after one year of antituberculosis
      treatment, (p < 0.05). Serum cortisol values in patients with drug-sensitive and
      drug-resistant tuberculosis did not differ significantly. Patients with drug
      resistant tuberculosis had a higher prevalence of adrenal gland enlargement (7 of
      the 30) as compared to those with drug-sensitive tuberculosis (7 of the 56) (p =
      NS). Subclinical adrenal insufficiency is prevalent in a significant number of
      patients with both drug-sensitive and drug-resistant tuberculosis, and in some of
      these it is associated with adrenal gland enlargement. The compromised adrenal
      reserve and enlargement seem to reverse with therapy.

PMID- 10916274
TI  - Role of computed tomography in patients with hemoptysis and a normal chest
      skiagram.
AB  - Thirty patients of hemoptysis with a normal skiagram chest were evaluated by
      computed tomography. Majority of the patients were between 21 to 50 years of age.
      Seventy percent had mild hemoptysis while 30 percent had moderate hemoptysis.
      Computed tomography provided diagnostic information in 16 patients (53%). The
      various aetiologies were bronchiectasis (20%), tuberculosis (20%), pneumonia
      (6.7%), bronchial carcinoid in one case and allergic bronchopulmonary
      aspergillosis in one case. Computed tomography may play a role in screening
      patients who present with hemoptysis with normal chest radiographs.

PMID- 10916273
TI  - Assessing severity of asthma: spirometric correlates with visual analogue scale
      (VAS).
AB  - BACKGROUND: Measurements of dyspnoea in asthma are difficult. Peak expiratory
      flow (PEF) and forced expiratory volume in first second (FEV1) are the most
      widely used objective measures of bronchial obstruction in asthma. Subjective
      continuous scales like visual analogue scale (VAS) provide a more flexible means
      of grading dyspnoea as perceived by the patient. METHODS: Utility of a VAS in
      assessing severity of bronchial asthma was evaluated in 195 previously diagnosed
      adult patients with bronchial asthma. Patients were asked to mark their severity
      as perceived by them on a continuous vertical VAS of 100 mm anchored at bottom
      with description no breathlessness' and at top by 'greatest breathlessness'. The
      distance measured from bottom in mm was taken as VAS score. This was correlated
      with FEV1 and PEF recorded immediately after the scale was marked. RESULTS: The
      mean VAS score was 31.13 (+/- 28.32) mm and had a good negative correlation with
      FEV1 (r = 0.5255, p < 0.01) and PEF (r = 0.4609, p < 0.01). Patients were also
      classified into four groups of mild, moderate, severe and acute asthma, and
      correlation analyzed in each group separately. The correlation was more
      significant in subgroups of moderate and severe asthma. Educational status of
      subjects had no impact on this correlation. CONCLUSION: VAS is a reasonable tool
      for measurement and monitoring of severity of asthma in individual patients, and
      may be used when more objective tests are not available.

PMID- 10916275
TI  - Non invasive ventilation in COPD.
AB  - Non invasive ventilation refers to the technique of providing ventilatory support
      without a direct conduit to the airway. It is a promising new technique, which is
      particularly useful in patients with COPD. Patients with COPD are prone to
      develop acute exacerbations, which pushes them into acute respiratory failure.
      Under these circumstances, tracheal intubation and mechanical ventilation is
      associated with significant morbidity and mortality. A number of well conducted
      studies support the fact that non invasive positive pressure ventilation (NIPPV)
      in these circumstances reduces rates of intubation, mortality, complications and
      duration of hospital stay. The biggest advantage of these techniques is their
      simplicity, ease of implementation and improved patient comfort allowing them to
      retain important functions like speech, cough and swallowing. NIPPV should be
      instituted early in the course of acute respiratory failure due to COPD before
      irreversible fatigue sets in. The current thinking is that NIPPV rests the
      respiratory muscles allowing other therapies time to be effective. Facilities for
      NIPPV should be available in all hospitals admitting patients with respiratory
      failure. Patients with severe, stable COPD who are hypercapnic and are
      deteriorating despite maximal conventional treatment should definitely be offered
      a trial of NIPPV. In such patients NIPPV has been shown to improve quality of
      life, reverse blood gas abnormalities, improve exercise tolerance and reduce
      hospital admissions. Physicians must familiarize themselves with this promising
      new ventilatory technique.

PMID- 10916276
TI  - Tracheobronchial amyloidosis: a report of two cases.
AB  - We describe here two patients with tracheobronchial involvement by amyloidosis.
      One of them had presented with discrete tracheobronchial mass lesions simulating
      bronchogenic carcinoma. The other had intermittent streaky hemoptysis and was
      found to have diffuse tracheobronchial involvement at bronchoscopy. Both patients
      are doing well without any definitive therapy.

PMID- 10916277
TI  - A case of recurrent pneumonias.
AB  - A description is given of the case of a young boy who presented with repeated
      episodes of pneumonias since childhood. In addition, he had episodes of
      intermittent diarrhoeas. His investigative work-up revealed a deficiency of serum
      immunoglobulins, that is, hypogammaglobulinaemia. The profile was suggestive of
      common variable immunodeficiency. Because of the relative rarity of this disease,
      it is often missed leading to significant morbidity. Treatment consists of
      immunoglobulin replacement therapy and management of recurrent infections with
      appropriate drugs.

PMID- 10916278
TI  - Metastatic adenocarcinoma rib presenting as chondrosarcoma.
AB  - A case of chondrosarcoma rib which turned out to be a case of metastatic
      adenocarcinoma on histopathological examination is being presented.

PMID- 10916279
TI  - World Health Organization. Fact sheet.

PMID- 10916280
TI  - Fabry disease: twenty-two novel mutations in the alpha-galactosidase A gene and
      genotype/phenotype correlations in severely and mildly affected hemizygotes and
      heterozygotes.
AB  - BACKGROUND: Fabry disease, an inborn error of glycosphingolipid catabolism,
      results from mutations in the X-chromosomal gene encoding the lysosomal
      exoglycosidase, alpha-galactosidase A (alpha-Gal A; EC 3.2.1.22). The nature of
      the molecular lesions in the alpha-Gal A gene in 36 unrelated families was
      determined in order to provide precise heterozygote detection, prenatal
      diagnosis, and to define genotype/phenotype correlations. METHODS: Genomic DNA
      was isolated from affected males and/or carrier females from 36 unrelated
      families with Fabry disease. The entire alpha-Gal A coding region and flanking
      intronic sequences were analyzed by PCR amplification and solid-phase or cycle
      sequencing. Markers closely linked to the alpha-Gal A gene were analyzed to
      determine if probands with the same mutations were related. RESULTS: Twenty-two
      novel mutations were identified including 10 missense (P40L, W95S, S148N, C172R,
      M187V, N224S, W226R, A230T, D266H, N320Y), three nonsense (Y134X, C142X, W204X in
      two families), three splice-site defects (IVS2(+1), IVS3(+1), IVS4(+1)) and six
      small deletions or insertions (26delA in two families, 672ins37, 774delAC,
      833insA, 1139delC, 1188insT). Of the remaining 12 families (33.3%), each had a
      previously identified mutation, eight of which occurred at CpG dinucleotides
      including R112C (two families), R112H, R227Q, R227X (three families), and R301Q.
      Haplotype analysis of the mutant alleles that occurred in two or three presumably
      unrelated families revealed that the families with the rare novel alleles (W204X
      and 26delA) were probably related, whereas those with mutations involving CpG
      dinucleotides (R112C and R227X) were not, the latter being consistent with their
      origins as independent mutational events. Genotype/phenotype correlations
      revealed that certain mutations previously found in mild variant patients also
      were found in classic patients. In addition, the genotypes and spectrum of
      phenotypic severity were determined in five heterozygotes with no family history.
      CONCLUSIONS: These results illustrate the molecular heterogeneity of the lesions
      causing Fabry disease and emphasize the fact that CpG dinucleotides constitute
      important hot spots for mutation in the alpha-Gal A gene. These studies also
      permit precise heterozygote detection and prenatal diagnosis in these families,
      and delineate phenotype-genotype correlations in this disease.

PMID- 10916281
TI  - Lack of association between the -308 polymorphism of the tumor necrosis factor
      alpha gene and the insulin resistance syndrome.
AB  - BACKGROUND: Previous studies have demonstrated a role for tumor necrosis factor
      alpha (TNF-alpha) in insulin resistance. A polymorphic variant of the TNF-alpha
      gene, the TNF2 allele, which is a guanine to adenine polymorphism at position 
      308 in the TNF-alpha promoter, is associated with higher basal and inducible
      promoter activity. The present study examined whether the TNF2 allele was
      associated with altered levels of different components of the insulin resistance
      syndrome, clustering of these components, or the 10-year change in the level of
      these components. METHODS: Components of the insulin resistance syndrome included
      insulin resistance, as determined by fasting insulin levels, body mass index,
      systolic blood pressure, triglycerides, uric acid, and high density lipoprotein
      cholesterol. The study population was a subsample of participants from the
      Coronary Artery Risk Development in (Young) Adults (CARDIA) study, which included
      African American and white men and women aged 18-30. The sample included 243
      black women, 142 black men, 392 white women, and 386 white men. Subjects were
      typed at the TNF-alpha locus. RESULTS: The frequency of the TNF2 allele was 12%
      in blacks and 16% in whites. Age-adjusted levels of the different components
      examined were not different at either baseline or year 10 in carriers of the TNF2
      allele versus homozygotes for the wild-type allele, and the 10-year change in the
      level of different components was not different between the two genotype groups.
      There also was no evidence of increased clustering of components of the insulin
      resistance syndrome in carriers of the TNF2 allele. Moreover, there was no
      evidence of an association between the TNF2 allele and clustering across
      quartiles of BMI or quartiles of dietary fat intake (i.e., Key's score).
      CONCLUSIONS: In African Americans and whites, neither the TNF2 allele nor another
      polymorphism in the TNF-alpha gene or a neighboring gene with which the TNF2
      allele is in linkage disequilibrium is associated with differences in the level
      of or increased clustering of components of the insulin resistance syndrome.

PMID- 10916282
TI  - Changes in LDL density across the menopausal transition.
AB  - BACKGROUND: The risk of coronary artery disease increases in women after
      menopause. This increased risk may be associated with alterations in the lipid
      profile characterized by changes in LDL particle size and buoyancy.
      Characterization of lipoprotein levels and LDL buoyancy across the stages of the
      menopausal transition has yet to be reported. METHODS: Plasma lipoprotein
      concentrations, LDL buoyancy, and body mass index (BMI) were studied cross
      sectionally in five groups of women: premenopausal women (n = 42), women in early
      menopausal transition (n = 35), middle menopausal transition (n = 19), late
      menopausal transition (n = 20), and postmenopausal women (n = 14). No women were
      taking estrogen. RESULTS: The postmenopausal women had significantly higher low
      density lipoprotein cholesterol (LDL-C) and total cholesterol than premenopausal
      women (P < 0.05). LDL-C and Apo B was significantly higher in women in the late
      menopausal transition compared to premenopausal women (P < 0.05). All women in
      the menopausal transition and postmenopause had significantly more dense LDL than
      premenopausal women (P < 0.05). Multiple regression analysis revealed that the
      change in LDL buoyancy associated with the menopausal transition period could be
      explained by changes in triglyceride and HDL-C, related to changes in body mass
      index. CONCLUSIONS: These data suggest that the menopausal transition is
      associated with more dense LDL and higher LDL-C levels in comparison to
      premenopausal women. It appears that whereas LDL-C may change late in the
      menopausal transition, the production of denser LDL particles appears early in
      the menopausal transition, both acting to worsen the lipoprotein profile.
      Increased triglyceride and decreased HDL appeared to account for the shift toward
      small, dense LDL, presumably related to increased BMI. The change in LDL density
      may contribute to the higher incidence of atherosclerosis in postmenopausal
      women.

PMID- 10916283
TI  - The effects of glucose and the hexosamine biosynthesis pathway on glycogen
      synthase kinase-3 and other protein kinases that regulate glycogen synthase
      activity.
AB  - BACKGROUND: Glycogen synthase (GS) activity is determined by its phosphorylation
      state. We have previously demonstrated that high glucose (HG) downregulates both
      basal and insulin-stimulated GS activity in rat-1 fibroblasts and that the
      hexosamine biosynthesis pathway (HBP) may be involved in mediating some of the
      effects of glucose. In this study we investigate the influence of high glucose
      and glucosamine (GlcN) on the activity of several kinases that phosphorylate and
      inactivate GS. METHODS: Glycogen synthase kinase (GSK) 3, cAMP-dependent protein
      kinase (PKA), protein kinase C (PKC), casein kinase (CK) 1, and phosphorylase
      kinase (PhK) activities were assayed in cellular extracts from control rat-1
      fibroblasts and those that overexpress human cDNA for glutamine:fructose 6
      phosphate amidotransferase (GFA), the rate-limiting enzyme in the HBP. RESULTS:
      Culturing rat-1 fibroblasts in HG (20 mmol/L) or GlcN (3-5 mmol/L) for 16-20
      hours increases GSK-3 activity by 23.9 and 50%, respectively, when compared to
      activity at low glucose (LG, 1 mmol/L). The effects of HG on GSK-3 activity are
      greater in cells overexpressing GFA (38.8% increase). Insulin (1.7 nmol/L)
      treatment leads to a 20-25% decrease in GSK-3 activity that is not affected by
      HG, GlcN, or GFA overexpression. Culturing control cells in HG increases PKA and
      CK-1 activities by 56 and 95%, respectively, and HG diminishes insulin action on
      CK-1 activity. GlcN inhibits insulin action on both PKA and CK-1 activities. HG,
      GlcN, and GFA overexpression blunted insulin's ability to downregulate PhK
      activity in LG conditions. PKC activity is not significantly altered in either
      cell line in the above conditions. CONCLUSIONS: These results suggest that HG
      alters both basal and insulin-regulated activity of several kinases that
      phosphorylate GS, and some of the effects of glucose may be mediated by its
      metabolism via the HBP.

PMID- 10916284
TI  - Regulation of Ca(2+)-activated K+ currents by ciglitazone in rat pituitary GH3
      cells.
AB  - BACKGROUND: Ciglitazone, an antidiabetic agent of the thiazolidinedione family,
      is known to be an activator of the peroxisome-proliferator activator receptor
      (PPAR)-gamma. The underlying mechanism of ciglitazone actions on ionic currents
      in neuroendocrine cells remains unclear. METHODS: The effects of ciglitazone on
      ionic currents were investigated in rat pituitary GH3 cells using the whole-cell
      and inside-out configurations of the patch-clamp technique. RESULTS: In GH3
      cells, ciglitazone at 3-300 mumol/L caused a reversible increase in the amplitude
      of the Ca(2+)-activated K+ current (IK(Ca)) with a half-maximal concentration of
      16 mumol/L. Under the inside-out patch recording mode, ciglitazone applied
      intracellularly increased the activity of the large-conductance Ca(2+)-activated
      K+ (BKCa) channels, but did not affect their single-channel conductance. However,
      troglitazone (30 mumol/L) caused a reduction in the channel activity. The
      ciglitazone-induced change in the kinetic behavior of BKCa channels is due to an
      increase in mean open time and a decrease in mean closed time, whereas the
      troglitazone-induced decrease in the channel activity is related to a decrease in
      mean open time and an increase in mean closed time. Ciglitazone caused a left
      shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated
      activity of BKCa channels is independent of internal Ca2+. Under the current
      clamp mode, ciglitazone (30 mumol/L) hyperpolarized the membrane potential.
      CONCLUSIONS: This study shows that in addition to its activation of PPAR-gamma,
      ciglitazone can stimulate the activity of BKCa channels expressed in GH3 cells.
      These effects may affect membrane potentials and contribute to the ciglitazone
      induced change in the functional activity of neurons or neuroendocrine cells.

PMID- 10916285
TI  - Excitatory lung reflex may promote inspiratory muscle fatigue in the rabbit.
AB  - BACKGROUND: Inspiratory muscle fatigue is common in severe pulmonary diseases and
      develops when the inspiratory effort quotient, which is the mean inspiratory
      pressure over maximal inspiratory pressure (PI/PIMAX), exceeds a critical value.
      If PIMAX is unchanged, increased PI will promote muscle fatigue. PI can be
      expressed as (k x VT/Cdyn) x (TI/TTOT), where k is a constant, VT is tidal
      volume, Cdyn is dynamic lung compliance, and TI/TTOT is inspiratory duty cycle,
      which is inspiratory time over the period of a respiratory cycle. The excitatory
      lung reflex (ELR), which can be evoked by inflammatory mediators (e.g., H2O2) or
      hypertonic saline to cause a vagally mediated neural hyperpnea and tachypnea, may
      be one of the mechanisms to promote inspiratory muscle fatigue. METHODS: To
      investigate whether the ELR can promote inspiratory muscle fatigue I conducted
      experiments in anesthetized and open-chest rabbits whose lungs were made
      motionless. The duty cycle, amplitude of the phrenic neurogram (which is closely
      correlated with VT), and burst rate were examined after initiation of the ELR by
      injection of hypertonic saline (8.1%, 0.1 mL) into the lung parenchyma. RESULTS:
      The duty cycle, amplitude, and burst rate of the phrenic activity increased by 36
      +/- 7, 15 +/- 3, and 40 +/- 8% (n = 9; P < 0.01), respectively. The responses
      were abolished by bilateral vagotomy. CONCLUSIONS: Because Cdyn and PIMAX did not
      change, the ELR increased the duty cycle, phrenic amplitude, and burst rate,
      therefore activation of this reflex may promote inspiratory muscle fatigue and
      may precipitate ventilatory failure.

PMID- 10916287
TI  - Statistical models for analysis of cytogenetic biomarkers.
AB  - BACKGROUND: Bleomycin-induced chromosomal breaks (CB) and sister chromatid
      exchange (SCE) in peripheral blood lymphocytes have been shown to be sensitive
      cytological markers for susceptibility to DNA damage in patients with various
      types of cancer and in healthy controls. Factors such as age, sex, smoking, and
      alcohol consumption could affect the values of some of these biomarkers and
      should be considered as covariates when analyzing cytogenetic biomarkers because
      these factors can affect the frequency of CB and SCE. METHODS: We propose a
      statistical method using negative binomial (NB) distribution to evaluate the
      numbers of CB and SCE. In order to determine the best model to represent the
      frequency of CB and SCE, we compared the NB model with the widely used Poisson
      model and log-transformed normal model by using generalized linear models. To
      demonstrate the better fit of the NB model, we analyzed three different data sets
      from studies conducted at The University of Texas M.D. Anderson Cancer Center.
      The first set was a case-control study of lung cancer in a population of African
      Americans and Mexican Americans (286 cases and 156 controls), the second set
      consisted of 311 head and neck cancer patients, and the third set consisted of
      105 Hodgkin's disease patients. RESULTS: For CB; the estimates of the variability
      for Hodgkin's disease, head and neck, and lung cancers were 487.24, 502.82, and
      520.15, respectively. For SCE, the estimates of the variability for Hodgkin's
      disease was 9777.01. For CB, the dispersion estimates under the three models
      (Poisson, NB, and Normal) for Hodgkin's disease, head and neck, and lung cancers
      were: 12.30, 1.20, 0.85; 8.94, 1.05, 0.22; and 10.10, 1.05, 0.25, respectively.
      For SCE (Hodgkin's disease only), the dispersion estimates under the three models
      (Poisson, NB, and Normal) were 30.91, 1.11, 0.10, respectively. CONCLUSIONS: Our
      results demonstrate that the NB model provides a better interpretation and fit
      for the frequency of CB and SCE in different cancer types. Therefore, we
      recommend it as a model for the analysis of cytogenetic biomarkers.

PMID- 10916286
TI  - Subclinical hepatic encephalopathy: role of tryptophan binding to albumin and the
      competition with indole-3-acetic acid.
AB  - BACKGROUND: The role of tryptophan (TRY) and its metabolites in the pathogenesis
      of hepatic encephalopathy is conflicting. The aim of the present study is to
      investigate in posthepatitis cirrhotic patients with encephalopathy the serum
      levels of TRY and those of its metabolite indole-3-acetic acid, as well as TRY
      binding curve to serum albumin and the competition with indole-3-acetic acid. The
      presence of a relationship between encephalopathy severity and circulating free
      TRY was also investigated. METHODS: Serum TRY and indole-3-acetic acid were
      analyzed by HPLC; binding of TRY to serum albumin and the competition with indole
      3-acetic acid was studied by equilibrium dialysis. RESULTS: Serum-free TRY was
      significantly higher in cirrhotic patients (43.33 +/- 14.70 vs 28.87 +/- 8.77
      mumol/L, P = 0.02). The binding capacity of albumin was reduced in cirrhotics and
      further decreased by the addition of indole-3-acetic (K = 6.63 +/- 0.97 x 10(3)
      mol/L-1, gamma = 1.16 +/- 0.45 x 10(2) mol/L-1 in normal sera vs K = 1.04 +/-
      0.20 x 10(3) mol/L-1, gamma = 1.91 +/- 0.92 10(2) mol/L-1 in cirrhotic sera). A
      multivariate analysis showed that among the psychometric tests the only
      independent predictor of serum levels of free TRY was the Block Design (R2 =
      0.94, B = 0.16 +/- 0.01, beta = 0.97; P < 0.0001). CONCLUSIONS: A high percent
      ratio of free/total TRY and indoleacetic acid (IAA) was found in cirrhotic
      patients with hepatic encephalopathy. The concentrations of serum-free IAA and
      TRY correlated with the degree of subclinical encephalopathy, suggesting a role
      of these compounds in the development of mental derangement in liver cirrhosis.

PMID- 10916288
TI  - Failure to incriminate domestic flies (Diptera: Muscidae) as mechanical vectors
      of Taenia eggs (Cyclophyllidea: Taeniidae) in rural Mexico.
AB  - Flies caught in homes in a rural village in Guerrero, Mexico, between November
      1994 and August 1995 were assessed for their role in the transmission of Taenia
      solium L. Most (99%) of the trapped flies were Musca domestica L. None of the
      1,187 guts or 1,080 legs of the flies contained T. solium eggs. Pigs roam freely
      in this village consuming human fecal material immediately after defecation,
      thereby limiting fly contact with T. solium eggs.

PMID- 10916289
TI  - Laboratory and field evaluation of polymerase chain reaction-based forensic DNA
      profiling for use in identification of human blood meal sources of Aedes aegypti
      (Diptera: Culicidae).
AB  - We modified polymerase chain reaction (PCR)-based forensic DNA profiling for
      field studies on the feeding behavior of Aedes aegypti, the principal mosquito
      vector of dengue virus. Human DNA was extracted from oral swabs of human subjects
      and from blood-engorged mosquitoes, DNA was quantified by slot blot, and alleles
      at variable number tandem repeats and three short tandem repeats loci were
      amplified by PCR. Alleles were separated electrophoretically and then visualized
      by silver staining. A custom software program was written to match DNA
      fingerprints of potential human hosts to allelic profiles detected in engorged
      mosquitoes, and to calculate error rates for identification of human hosts of
      single and multiple-host blood meals. At 29 degrees C in the laboratory, human
      DNA recovered from mosquito blood meals declined an average of 67% 8 h after
      feeding and 90% after 24 h. We obtained complete allelic profiles from seven of
      10 mosquitoes collected after 24 h. In a field trial, complete DNA profiles were
      obtained successfully for 43 people living in a rural village in south central
      Thailand and for 20 of 100 Ae. aegypti that contained blood and were collected in
      those peoples' homes. Blood imbibed from more than one person was detected in 45%
      (9 of 20) of the meals. Sixty-five percent of the meals contained blood from
      nonresidents of the house in which the mosquito was collected or from people who
      were not profiled; data consistent with the hypothesis that human movement is
      important for the spread of dengue virus within and among communities. When using
      alleles at four loci, all of the Thais and nine members spanning three
      generations of a Chinese-American family had unique allelic profiles. Error rates
      from classifying possible multiple-host meals as single-host meals were low (1
      8%), with the highest error associated with closely related people. Results from
      our laboratory and field studies indicated that DNA profiling can be used to
      study the details and epidemiological implications of Ae. aegypti blood-feeding
      behavior.

PMID- 10916290
TI  - Effect of pyriproxyfen in the blood diet of cat fleas on adult survival, egg
      viability, and larval development.
AB  - The activity of pyriproxyfen in the blood diet was investigated for its efficacy
      against adult, egg, and larval stages of the cat flea, Ctenocephalides felis
      (Bouche). Adult fleas were housed in plastic cages and fed treated bovine blood
      using an artificial membrane system that allows fleas to feed ad libitum through
      a parafilm membrane. Control fleas received blood without pyriproxyfen. Results
      showed that ingested pyriproxyfen was relatively nontoxic to adult fleas over a
      period of 10 d at concentrations as high as 100 ppm. These findings are in sharp
      contrast to earlier studies that showed that residues of pyriproxyfen on filter
      paper or dog hair were highly toxic to adult cat fleas at concentrations as low
      as 12.5 ppm. Fleas obviously fed on blood containing pyriproxyfen because they
      produced large numbers of eggs. However, none of the eggs hatched. Also, larvae
      of untreated fleas failed to develop to adults when they were fed fecal blood
      excreted by pyriproxyfen-treated fleas. The results indicate that although
      ingested pyriproxyfen was relatively nontoxic to adult fleas, enough chemical was
      absorbed through the gut wall to cause ovisterilant activity, while the remainder
      was excreted.

PMID- 10916291
TI  - Patterns of avian seroprevalence to western equine encephalomyelitis and Saint
      Louis encephalitis viruses in California, USA.
AB  - Temporal and spatial changes in the enzootic activity of western equine
      encephalomyelitis (WEE) and St. Louis encephalitis (SLE) viruses were monitored
      at representative wetland study sites in the Coachella, San Joaquin, and
      Sacramento valleys of California from 1996 to 1998 using three methods: (1) virus
      isolation from pools of 50 host-seeking Culex tarsalis Coquillett females, (2)
      seroconversions in flocks of 10 sentinel chickens, and (3) seroprevalence in wild
      birds collected by mist nets and grain baited traps. Overall, 74 WEE and one SLE
      isolates were obtained from 222,455 Cx. tarsalis females tested in 4,988 pools.
      In addition, 133 and 40 seroconversions were detected in 28 chicken flocks, and
      143 and 27 of 20,192 sera tested from 149 species of wild birds were positive for
      antibodies to WEE and SLE, respectively. WEE was active in all three valleys,
      whereas SLE only was detected in Coachella Valley. Seroconversions in sentinel
      chickens provided the most sensitive indication of enzootic activity and were
      correlated with seroprevalence rates in wild birds. Avian seroprevalence rates
      did not provide an early warning of pending enzootic activity in chickens,
      because positive sera from after hatching year birds collected during spring most
      probably were the result of infections acquired during the previous season. Few
      seroconversions were detected among banded recaptured birds collected during
      spring and early summer. Age and resident status, but not sex, were significant
      risk factors for wild bird infection, with the highest seroprevalence rates among
      after hatching year individuals of permanent resident species. Migrants (with the
      exception of mourning doves) and winter resident species rarely were positive.
      House finches, house sparrows, Gambel's quail, California quail, common ground
      doves, and mourning doves were most frequently positive for antibodies. The
      initial detection of enzootic activity each summer coincided closely with the
      appearance of hatching year birds of these species in our study areas, perhaps
      indicating their role in virus amplification. Bird species most frequently
      positive roosted or nested in elevated upland vegetation, sites where Cx.
      tarsalis host-seeking females hunt most frequently. These serosurveys provided
      important background information for planned host competence and chronic
      infection studies.

PMID- 10916292
TI  - Tagging bloodmeals with phagemids allows feeding of multiple-sample arrays to
      single cages of mosquitoes (Diptera: Culicidae) and the recovery of single
      recombinant antibody fragment genes from individual insects.
AB  - A recombinant single-chain variable-region human antibody fragment (scFv) was
      expressed in Escherichia coli, extracted in hypertonic sucrose, mixed directly
      with blood and fed to Anopheles gambiae Giles mosquitoes. When E. coli containing
      the phagemids that encode these scFv were included in bloodmeals, phagemids could
      be recovered from the mosquito midgut for up to 3 d after feeding. Furthermore,
      large arrays of such gene-tagged scFv-containing bloodmeals could be fed to cages
      of mosquitoes using microtiter plates. Arrays of phagemids with and without an
      antibody insert were fed to single cages of mosquitoes to test whether individual
      mosquitoes fed from single wells of such arrays. Phagemids were recovered from
      95% of blood-fed females and > 80% of these phagemids were monoclonal. Therefore,
      it is possible to feed multiple sample arrays of recombinant proteins to single
      cages of mosquitoes and to recover the genetic material that encodes for only one
      of the array elements from individual mosquitoes. This demonstration indicates
      that multiple-sample feeding and recovery strategies are feasible and may
      represent a viable strategy for future rapid screening of biologically active
      genes, gene products or microorganisms in live arthropods.

PMID- 10916293
TI  - Laboratory selection for resistance to Bacillus sphaericus in Culex
      quinquefasciatus (Diptera: Culicidae) from California, USA.
AB  - A previously untreated field population of Culex quinquefasciatus Say, collected
      near Bakersfield, CA, was subjected to intensive laboratory selection with the
      bacterial insecticide Bacillus sphaericus Neide (strain 2362) at a level
      producing 95% mortality. Resistance rapidly appeared and resistance levels
      increased such that fourth instars of generation 12 were able to survive a
      concentration of B. sphaericus that was 7,000 times higher than the median lethal
      concentration (LC50) of the susceptible reference colony. Similar resistance
      levels were detected in first instars. Cross-resistance in the selected colony
      was detected toward B. sphaericus strains 1593 and 2297, but little or no cross
      resistance was observed toward B. sphaericus strains IAB59 or ISPC5 (= WHO 2173).
      Cross-resistance also was not detected toward the bacterial insecticide Bacillus
      thuringiensis subsp. israelensis, toward a recombinant strain expressing both B.
      thuringiensis subsp. israelensis and B. sphaericus (strain 1593) toxins, toward
      individual or multiple toxins from B. thuringiensis subsp. israelensis, or toward
      conventional synthetic insecticides. Genetic analysis revealed that B. sphaericus
      resistance was inherited as a recessive trait and controlled by a single major
      locus. These data are discussed in relation to cases of field resistance toward
      this biopesticide in the Cx. pipiens (L.) complex.

PMID- 10916294
TI  - Behavior of resting Aedes aegypti (Culicidae: Diptera) and its relation to ultra
      low volume adulticide efficacy in Panama City, Panama.
AB  - The resting behavior of Aedes aegypti (L.) adults was investigated in 14
      districts of Panama City, Panama, in relation to ground ultra-low volume (ULV)
      applications of malathion. Adults primarily rested inside the premises (75.1%) at
      a distance > 6 m from the street (86.4%). Both sexes rested mainly in bedrooms,
      living rooms, and bathrooms. The small ULV aerosol droplets (2-4 microns)
      penetrated all indoor resting sites of Ae. aegypti, but in low amounts. Because
      of the low amount of insecticide reaching the primary resting sites within the
      premises, limited control of the Ae. aegypti was obtained. This limited the
      potential effectiveness of ground vehicle ULV applied insecticide as a dengue
      epidemic control method.

PMID- 10916295
TI  - Cytotaxonomic and molecular analysis of Simulium (Edwardsellum) damnosum sensu
      lato (Diptera: Simuliidae) from Abu Hamed, Sudan.
AB  - The northernmost focus for Onchocerca volvulus Leuckhart (Nematoda:
      Onchocercidae), the causative agent of human onchocerciasis, is found along the
      Nile near the town of Abu Hamed in Sudan. The vector for O. volvulus at this
      focus is a single monomorphic population of Simulium (Edwardsellum) damnosum
      Theobald. This black fly population is limited to a small area between the fourth
      and fifth cataracts of the Nile River that is isolated geographically from all
      other populations of S. damnosum sensu lato. Phylogenies produced from
      cytological analyses and sequence data derived from the NADH dehydrogenase
      subunit 4 and 16S rRNA genes indicate that Abu Hamed black flies are similar to,
      but distinct from, the savanna-dwelling sibling species of S. damnosum s.l.,
      Simulium (Edwardsellum) damnosum sensu strictu Theobald, and S. (Edwardsellum)
      sirbanum Vajime & Dunbar. The DNA sequence and the cytological data support the
      hypothesis that the black fly population present in Abu Hamed may represent a new
      sibling species of S. damnosum s.l. We propose that this population be informally
      designated as the hamedense form of the Simulium damnosum complex.

PMID- 10916296
TI  - Identification of Culex vishnui subgroup (Diptera: Culicidae) mosquitoes from the
      Ryukyu Archipelago, Japan: development of a species-diagnostic polymerase chain
      reaction assay based on sequence variation in ribosomal DNA spacers.
AB  - The Culex vishnui subgroup includes three important vectors of Japanese
      encephalitis virus, Culex tritaeniorhynchus Giles, Cx. pseudovishnui Colless, and
      Cx. vishnui Theobald, all of which occur in the Ryukyu Archipelago, Japan.
      Although these three species have been shown to be vectors of JE virus in many
      areas of Southeast Asia, it is not yet known what role each plays in the
      transmission of the virus in this region. Reliable identification of adult, field
      collected specimens is a critical component in epidemiological studies of virus
      transmission. Mosquitoes in the Cx. vishnui subgroup can be reliably identified
      in the larval stage. However, because females of these species are very similar,
      it is difficult to distinguish among them using morphology. We developed a
      polymerase chain reaction (PCR) assay for the identification of these species.
      Three species-specific primers were developed for the PCR assay based on a
      comparative analysis of the nucleotide sequence of the first internal transcribed
      spacer (ITS1) in the ribosomal DNA gene array. The primers, CT2REV, CP1REV, and
      CV1REV were designed to amplify a single DNA fragment each from Cx.
      tritaeniorhynchus, Cx. pseudovishnui, and Cx. vishnui, respectively, when paired
      with a single forward primer that is complementary to the highly conserved 18S
      rDNA gene. The amplified fragments were separated easily and identified on an
      agarose gel to facilitate species identification.

PMID- 10916297
TI  - La Crosse encephalitis virus habitat associations in Nicholas County, West
      Virginia.
AB  - Aedes triseriatus (Say) population density patterns and La Crosse encephalitis
      virus infection rates were evaluated in relation to a variety of habitat
      parameters over a 14-wk period. Ovitraps and landing collections were used in a
      La Crosse virus-enzootic area in Nicholas County, WV. Study sites were divided
      into categories by habitat type and by proximity to the residences of known La
      Crosse encephalitis cases. Results demonstrated that Ae. triseriatus population
      densities were higher in sugar maple/red maple habitats than in hemlock/mixed
      hardwood habitats or in a site characterized by a large number of small red maple
      trees. Sites containing artificial containers had higher population densities
      than those without. La Crosse virus minimum infection rates in mosquitoes
      collected as eggs ranged from 0.4/1,000 to 7.5/1,000 in the 12 study sites, but
      did not differ significantly among sites regardless of habitat type or proximity
      to human case residences. La Crosse virus infection rates in landing Ae.
      triseriatus mosquitoes ranged from 0.0/1,000 to 27.0/1,000. La Crosse virus was
      also isolated from host-seeking Ae. canadensis (Theobald) in two study sites, at
      rates similar to those found in the Ae. triseriatus populations. The Ae.
      triseriatus oviposition patterns and La Crosse virus infection rates suggest that
      this mosquito species disperses readily in the large woodlands of central West
      Virginia. The La Crosse enzootic habitats in Nicholas County, WV, are contrasted
      with those studied in other geographic regions where La Crosse virus is found.

PMID- 10916298
TI  - Development of an assay for the screening of compounds against larvae of the cat
      flea (Siphonaptera: Pulicidae).
AB  - Larvae of the cat flea, Ctenocephalides felis (Bouche), are the target of
      numerous growth regulators. This study explores the development of an assay that
      tests the susceptibility of cat flea larvae to a wide range of compounds.
      Different rearing media and containment units were tested that would facilitate
      optimization. Larvae of various ages were compared, and 7-d-old larvae were found
      to be optimal because they were the most uniform in size and age and exhibited a
      need to feed. The assay could be used to distinguish insecticides from growth
      inhibitors. The insecticides chlorpyrifos and carbaryl caused 100% larval
      mortality in 24 h at 10 ppm, and cythioate and fipronil killed the larvae at
      concentrations of > or = 100 ppm within 24 h. The insect growth regulators
      methoprene and pyriproxifen caused molt delay at concentrations of 100 ppm and
      bioallethrin delayed molt at 1,000 ppm. This assay can be used to identify
      compounds that are specific to cat flea larvae that may be useful in the control
      of cat flea infestations.

PMID- 10916299
TI  - Morphology of larval antennae and mouthparts of four Indian sand flies (Diptera:
      Psychodidae) by scanning electron microscopy.
AB  - The mouthparts and antennae of the fourth-instar larvae of four sand fly species
      were studied using scanning electron microscopy. The morphology of the clypeus,
      labrum, mandible, maxilla, mentum, and antennae were compared for Phlebotomus
      argentipes Annandale & Brunetti, P. papatasin (Scopoli), Sergentomyia babu babu
      (Annandale), and S. bailyi (Sinton). Most of structures exhibited species
      specific features, particularly the characteristics of the antennae. P. papatasin
      larvae had heart-shaped antennae, a long mandible, stout maxilla, and a heavy
      mentum with large teeth. In contrast, P. argentipes larvae had dumbbell-shaped
      antennae and a singular club-shaped labrum. The antennae of S. b. babu were
      ovoid, whereas those of S. bailyi were elliptical. The labrum of S. b. babu was
      lanceolate, whereas that of S. bailyi was rounded and exhibited a small, thick
      projection with several folds. The teeth of the mentum of both Sergentomyia
      species were shorter than those of the Phlebotomus species. Species-specific
      differences in the morphology of larval mouthparts and antennae indicate that it
      may not always be necessary to rely on adult morphology to identify sympatric
      phlebotomines.

PMID- 10916300
TI  - Development and evaluation of a dipstick assay for detection of Plasmodium
      falciparum and P. vivax sporozoites in mosquitoes (Diptera: Culicidae).
AB  - We developed a nitrocellulose-based, dipstick circumsporozoite (CS)-enzyme
      immunoassay [ELISA] for the simultaneous detection of Plasmodium falciparum and
      P. vivax-210 CS protein. The assay had a detection threshold of < 250 P.
      falciparum or 400 P. vivax sporozoites per sample, gave results concordant with
      dissection of salivary glands and CS-ELISA, but was slightly less sensitive than
      the CS-ELISA in microtiter plates. The assay consistently detected one infected
      mosquito in a pool of 10 or 20 mosquitoes, and was 100% specific in
      discriminating between species of Plasmodium when mosquito suspensions were
      spiked with sporozoites. The assay could be completed in 1 h, required no
      specialized equipment, and therefore was useful for field applications.

PMID- 10916301
TI  - The '4-poster' passive topical treatment device to apply acaricide for
      controlling ticks (Acari: Ixodidae) feeding on white-tailed deer.
AB  - A '4-poster' device that attracts white-tailed deer to a bait source, and as they
      feed, allows a self-application of a pesticide to the head, ears, and neck to
      control ticks was designed, constructed, and tested. The device consists of a
      central bin containing bait to attract deer and two feeding and application
      stations. These stations each have one bait port and two vertical pesticide
      impregnated applicator rollers. This design allows unrestricted vertical
      retraction of the head to minimize injury to the deer or damage to the posts
      supporting the pesticide application rollers. Observations using deer
      demonstrated ready acceptance and repeated use by both antlered and antlerless
      deer. Results of an initial trial indicate that control values for lone star
      ticks, Amblyomma americanum (L.), exceeded 92-97% on deer that used the device
      regularly.

PMID- 10916302
TI  - Distribution of Ehrlichia chaffeensis (Rickettsiales: Rickettsiaeceae) in
      Amblyomma americanum in southern Indiana and prevalence of E. chaffeensis-
      reactive antibodies in white-tailed deer in Indiana and Ohio in 1998.
AB  - To continue monitoring the prevalence and distribution of Ehrlichia chaffeensis
      (Rickettsiales: Rickettsiaeceae) in southern Indiana, a total of 498 Amblyomma
      americanum (L.) ticks (262 adults and 292 nymphs) was collected from five
      southern Indiana counties during May and June 1998. Ticks were pooled and
      examined for the presence of E. chaffeensis using nested polymerase chain
      reaction and primers specific for the 16S rRNA gene of E. chaffeensis. The
      average minimum infection rate for adult ticks collected in 1998 was 3.8%
      (ranging from 0 to 7.7% in various counties) as compared with previous average
      minimum infection rates of 1.6% in 1995 and 4.9% in 1997. None of the pools of A.
      americanum nymphs tested positive. In addition, blood samples were collected from
      325 white-tailed deer taken in Indiana and 327 taken in Ohio in November 1998.
      Serum samples were tested for the presence of E. chaffeensis-like organisms
      reactive to antibodies using an indirect immunofluorescence assay (IFA).
      Antibodies were found in deer from six Indiana counties where infection rates
      ranged from 42.6 to 66.7% and in four Ohio countries where infection rates ranged
      from 4.4 to 25%. The results of this study reconfirm that E. chaffeensis is well
      established in southern Indiana and also provide the first evidence of E.
      chaffeensis-like organisms infecting white-tailed deer in Ohio, suggesting the
      need to survey Ohio ticks for the presence of Ehrlichia.

PMID- 10916303
TI  - Performance of female Rhipicephalus sanguineus (Acari: Ixodidae) fed on dogs
      exposed to multiple infestations or immunization with tick salivary gland or
      midgut tissues.
AB  - This investigation compared the effects of repeated infestations to immunization
      of dogs with tick salivary gland or midgut extracts on the feeding and fecundity
      performances of female Rhipicephalus sanguineus (Latrielle). In each immunized
      group, three tick-naive dogs were immunized three times with tick salivary gland
      or midgut extracts, and twice challenged at 21-d intervals by allowing 80 female
      and 40 male adult ticks to feed on each host. The repeated infestation group of
      three naive dogs was infested five times at 21-d intervals by the same numbers of
      ticks. The repeated infestation group showed a trend of reduced tick performance
      after the third infestation, but some of the tick performance parameters had
      recovered by the fifth infestation. Tick attachment was reduced by immunization
      with either tick salivary gland or midgut extract. Immunization with tick
      salivary gland extract had the greatest impact on the feeding period and
      engorgement weight of the female ticks. Immunization with tick midgut extract
      resulted in the greatest reduction of tick fecundity parameters, which included
      preoviposition, oviposition, and egg-incubation periods in addition to reduced
      egg production and egg viability. These results confirm that dogs can become
      resistant to R. sanguineus, and demonstrate that immunization with tick salivary
      gland or midgut extract has different effects on tick feeding and fecundity.

PMID- 10916304
TI  - Effects of pyriproxyfen spray, powder, and oral bait treatments on the relative
      abundance of nontarget arthropods of black-tailed prairie dog (Rodentia:
      Sciuridae) towns.
AB  - Separate black-tailed prairie dog, Cynomys ludovicianus (Ord), towns on the Rocky
      Mountain Arsenal National Wildlife Refuge, Colorado, were treated with technical
      pyriproxyfen (Nylar) spray, powder, and oral bait. The treatments were applied to
      reduce relative abundance of the plague vector Oropsylla hirsuta (Baker). Because
      pyriproxyfen is a juvenile hormone analog, we were also concerned with the
      effects of the treatments on nontarget arthropods, which is the focus of this
      study. Pitfall traps and sweep net sampling were used to measure relative
      abundance of arthropod populations pre- and posttreatment. Nontarget arthropod
      sampling produced a large number of statistical comparisons that indicated
      significant declines (P < 0.05) in relative arthropod abundance. Many of the
      significant declines were probably because of natural fluctuations in arthropod
      populations rather than treatment effects. Because arthropod populations appeared
      to fluctuate randomly, we only made inferences about highly significant (P <
      0.001) declines. In doing so, we hoped to abate some of the confusion created by
      the natural fluctuation in arthropod abundance and increase our chance of
      correctly attributing a population reduction to a treatment effect. Only
      Homoptera at the pyriproxyfen powder site exhibited highly significant reductions
      that appeared to be attributed to the treatments. Pyriproxyfen spray treatments
      did not significantly reduce relative arthropod abundance.

PMID- 10916305
TI  - Infection of aquatic insects with trematode metacercariae carrying Ehrlichia
      risticii, the cause of Potomac horse fever.
AB  - We provide evidence of Ehrlichia risticii Holland, the agent of Potomac horse
      fever, in trematode stages found in aquatic insects collected from a pasture
      stream in northern California, using nested polymerase chain reaction (PCR)
      amplification and sequence analyses of the 16S rRNA, 51 kDa major antigen and
      groEL heat shock protein genes. E. risticii was detected in metacercariae found
      in the immatures and adults of the following insects: caddisflies (Trichoptera),
      mayflies (Ephemeroptera), damselflies (Odonata, Zygoptera), dragonflies (Odonata,
      Anisoptera), and stoneflies (Plecoptera). The prevalence of E. risticii was 31.9%
      (n = 454 individuals) in aquatic insects (13 of 17 species were positive).
      Prevalence within orders was as follows: 43.5% (n = 207) in caddisflies, 15.2% (n
      = 92) in mayflies, 13.9% (n = 115) in damselflies, 10.0% (n = 10) in dragonflies,
      and 80.0% (n = 30) in stoneflies. This study demonstrates a broad intermediate
      host range for trematodes that act as vector for E. risticii. Insects are likely
      to play an important role in the epidemiology of this disease.

PMID- 10916306
TI  - Frequency of Saint Louis encephalitis virus in humans from Florida, USA: 1990
      1999.
AB  - Four general frequencies of human St. Louis encephalitis (SLE) virus (epidemic,
      focal, sporadic, and no transmission) occurred in Florida between 1990 and 1999.
      An epidemic with 226 clinical cases and 11 deaths was reported from 28 Florida
      counties between July 1990 and January 1991. During the autumn of 1993, a focal
      outbreak was reported from Lee (5 cases) and Collier (3) Counties in southwest
      Florida. During the autumn of 1997, sporadic transmission to nine humans was
      reported from five Florida counties (Brevard [1 case], Polk [3], Charlotte [1],
      Lee [2], and Palm Beach [2]). Human infection with SLE virus depends on a number
      of variables that drive virus transmission. These include vector, virus, and
      avian host abundance, and meteorological events, especially rainfall. We
      monitored the abundance and serological status of wild avian amplification hosts,
      virus isolations from Culex nigripalpus Theobald females, and SLE virus
      transmission to sentinel chickens during 1990, 1993, and 1997. The epidemic of
      1990 was characterized by conditions that produced an unusual abundance of vector
      mosquitoes and avian amplification hosts early in the year. We propose that
      epidemics may result when a specific combination of biotic and abiotic conditions
      favor SLE virus minimum field infection rates that approach 1:1,000 in Cx.
      nigripalpus vectors.

PMID- 10916307
TI  - First bloodmeal of Ctenocephalides felis felis (Siphonaptera: Pulicidae) on cats:
      time to initiation and duration of feeding.
AB  - Three experiments were conducted on cats to evaluate precocity and duration of
      the first blood meal of Ctenocephalides felis felis (Bouche). Percentage of
      engorged fleas was calculated for fleas held on cats for 5, 15, 30, and 60 min.
      Duration of first blood meal was also measured for individual fleas confined on
      cats. When fleas are free in the hair coat, 24.9% are engorged after 5 min and
      97.2% are engorged after 1 h. Fleas confined to a vial on the cats fed
      significantly sooner; 60% of females were engorged within 5 min. The mean delay
      between deposition and biting for fleas, which began feeding within 15 min, was
      24 s +/- 31 s for females and 23 s +/- 44 s for males. The mean duration of meals
      was 25 +/- 18 min for females and 11 +/- 8 min for males.

PMID- 10916308
TI  - Proboscis amputation facilitates the study of mosquito (Diptera: Culicidae)
      attractants, repellents, and host preference.
AB  - Proboscis amputation has facilitated the study of mosquito behavior. Using humans
      as a host is very important in the study of mosquito attractants, repellents, and
      host preference. However, mosquito bites cause potential medical problems because
      of hypersensitivity and perhaps secondary bacterial infection, even using
      laboratory mosquitoes. Moreover, once a normal female mosquito bites and feeds on
      human blood, it cannot be used in subsequent probing tests. These problems were
      resolved by proboscis amputation. Variation of attraction among humans was
      examined effectively without bites using proboscis-amputated Aedes albopictus
      Skuse. Proboscis-amputated and normal mosquitoes also showed equal repellency
      against 1% L-lactic acid. Although the mosquitoes lacked the tip of the labium
      and some sensilla, they alighted on human forearms in the same way as normal
      mosquitoes. Because proboscis-amputated mosquitoes continued to probe avidly,
      they could be used repeatedly, thereby reducing the number of mosquitoes required
      for experimentation. The use of proboscis-amputated mosquitoes would promote
      various studies of mosquito attraction or repellency with no risk of
      hypersensitivity and secondary bacterial infection by mosquito bites.

PMID- 10916309
TI  - New host and distribution record of Amblyomma javanense (Acari: Ixodidae) in
      Thailand.
AB  - Amblyomma javanense (Supino) was collected from a Malayan pangolin (Manis
      javanica Desmarest) and a wild boar (Sus scrofa L.) from Tak province on the
      western boundary of Thailand along the Myanmar (Burma) border. To date, this tick
      species has not been recorded from this area and from a wild boar.

PMID- 10916310
TI  - Failure of dengue-2 virus antibody to interfere with the isolation of dengue-2
      virus from Aedes aegypti (Diptera: Culicidae).
AB  - When isolating dengue virus (DEN) from mosquitoes collected in endemic areas,
      pools may contain both anti-dengue antibodies from freshly engorged females and
      virus from DEN infected females. To determine if these antibodies may interfere
      with virus isolation, we simulated the isolation procedure using Aedes aegypti
      (L.) that we infected with the 16,681 strain of dengue type 2 virus by
      intrathoracic inoculation. At 7 d postinfection, we allowed females to engorge on
      immunized or normal mouse blood. Virus in a mixture of anti-dengue-2 antibodies
      and dengue-2 virus became inactive after incubation at 37 degrees C for 1 h, but
      remained infective without incubation. Therefore, at ambient conditions
      antibodies would not interfere with virus isolation from field-collected Ae.
      aegypti from endemic areas. In addition, DEN antibodies enhanced virus
      replication when inoculated into Ae. aegypti, but not C6/36 cells. The mechanism
      for this in vitro antibody enhancement of infection remains unclear.

PMID- 10916311
TI  - The geographic distribution of AIDS in the United States: is there a rural
      epidemic?
AB  - The goal of this study was to examine where people with acquired immune
      deficiency syndrome (AIDS) in the United States live and the degree to which AIDS
      is present in rural areas. AIDS cases reported to the Centers for Disease Control
      and Prevention (CDC) in 1996 were categorized by metropolitan statistical area
      (MSA) size and compared to the general population. Data were analyzed by region,
      race/ethnicity and risk exposure; AIDS incidence rates were compared over time by
      MSA size. Relative to the U.S. population, AIDS cases were disproportionately
      black (43 percent vs. 11 percent), male (80 percent vs. 48 percent), and from the
      Northeast (32 percent vs. 20 percent). In all regions, a greater proportion of
      AIDS cases reside in large MSAs compared with the general population. Risk
      exposures differ little by MSA size, except in the Northeast. The proportion of
      people with AIDS who reside in large MSAs exceeds the proportion of the
      population in those areas, especially when race/ethnicity is considered. AIDS
      rates have increased in non-MSAs relative to large MSAs, yet do not indicate that
      the epidemic is increasing rapidly in rural areas. Fewer AIDS cases are reported
      from smaller communities, yet require medical and social services that may burden
      the rural health care system.

PMID- 10916312
TI  - Human immunodeficiency virus infection in rural areas and small cities of the
      southeast: contributions of migration and behavior.
AB  - The design of education and prevention strategies to stem the spread of human
      immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) in
      rural areas depends on having accurate patterns of risk behavior and transmission
      in local areas. Interviews were conducted with people in rural areas and small
      cities in Delaware, Florida, Georgia and South Carolina who were at least 18
      years old and infected with HIV in order to describe demographic characteristics,
      migration patterns and risk behaviors. Interviews were conducted with 608 people.
      Most respondents were male (66 percent), black (63 percent of men, 85 percent of
      women) and had been infected through sexual contact (67 percent of men, 66
      percent of women). Most (65 percent) had lived away from a rural area or small
      city for at least one month; of those, 71 percent had moved from an urban area.
      Twenty-seven percent of respondents indicated they had been infected locally.
      People with a history of injection drug use were less likely to have been
      infected locally than those who had no history of injection drug use (6 percent
      vs. 26 percent among men, 3 percent vs. 40 percent among women, P < 0.001).
      Further understanding of the role of socioeconomic factors in HIV transmission in
      rural areas and small cities is needed. Programs designed to prevent HIV
      acquisition among people living in rural areas and small cities in the Southeast
      should focus on sexual behavior.

PMID- 10916313
TI  - Access to care for rural Medicare beneficiaries.
AB  - This paper examines variations between urban and rural Medicare beneficiaries in
      three measures of access to care: self-reported access to care, satisfaction with
      care received and use of services. The assessment focuses on these measures and
      their relationship to adjacency to metropolitan areas. Comparisons are also
      provided for the relative effects of adjacency versus broader access barriers
      such as income. Data from the 1993 Medicare Current Beneficiary Survey are used.
      The analyses offer several new perspectives on access in rural areas. First, as
      perceived by respondents, rural residence does not indicate access problems;
      instead, Medicare beneficiaries in rural counties that are adjacent to urban
      areas and that have their own city of at least 10,000 people report higher levels
      of satisfaction and fewer self-reported access problems than do residents of
      urban counties. These results may stem either from differences in rural
      residents' expectations regarding access or willingness to accept appropriate
      substitutions. Preventive vaccination rates in rural areas are on par with or
      better than rates by beneficiaries in urban areas. The only services where
      utilization in rural areas was limited relative to urban areas were preventive
      cancer screening for women and dental care. Development of policies to address
      these specific service gaps may be warranted. Low income has a more pervasive and
      problematic relationship to self-reported access, satisfaction and utilization
      than does rural residence per se.

PMID- 10916314
TI  - Socioeconomic distress and health status: the urban-rural dichotomy of services
      utilization for people with sickle cell disorder in North Carolina.
AB  - Research on sickle cell disorder has not focused attention on the socioeconomic
      background and geographic distribution of people with the disease. This study
      examines 1,189 persons with sickle cell disorder in North Carolina during 1991 to
      1995. Three indices were developed using clients' medical, psychosocial and
      socioeconomic characteristics for the purpose of analyzing the urban-rural
      difference in treatment for sickle cell disease. The study observed a wide
      disparity in these indices between urban and rural population groups. Also,
      differences were observed in the utilization of services and clients' health
      status. The findings suggest that utilization of services is directly related to
      socioeconomic condition facing clients and clinic distance from clients. They
      further suggest that people in rural areas who have high distress levels and are
      far from clinics have limited access to health care. The limited availability of
      medical and health care in rural areas, as well as other support systems calls
      for an increase in community based healthcare services. These findings should be
      of particular interest to the state level sickle cell disorder program in North
      Carolina and other areas with a large rural population. Enhanced support for all
      persons with sickle cell disorder in North Carolina, particularly those in rural
      areas, is critical.

PMID- 10916315
TI  - Educating generalist physicians for rural practice: how are we doing?
AB  - Although about 20 percent of Americans live in rural areas, only 9 percent of
      physicians practice there. Physicians consistently and preferentially settle in
      metropolitan, suburban and other nonrural areas. The last 20 years have seen a
      variety of strategies by medical education programs and by federal and state
      governments to promote the choice of rural practice among physicians. This
      comprehensive literature review was based on MEDLINE and Health STAR searches,
      content review of more than 125 relevant articles and review of other materials
      provided by members of the Society of Teachers of Family Medicine Working Group
      on Rural Health. To the extent possible, a particular focus was directed to
      "small rural" communities of less than 10,000 people. Significant progress has
      been made in arresting the downward trend in the number of physicians in these
      communities but 22 million people still live in health professions shortage
      areas. This report summarizes the successes and failures of medical education and
      government programs and initiatives that are intended to prepare and place more
      generalist physicians in rural practice. It remains clear that the educational
      pipeline to rural medical practice is long and complex, with many places for
      attrition along the way. Much is now known about how to select, train and place
      physicians in rural practice, but effective strategies must be as multifaceted as
      the barriers themselves.

PMID- 10916317
TI  - Delivering mental health services to the persistently and seriously mentally ill
      in frontier areas.
AB  - Frontier areas (defined as six or fewer persons per square mile) are at the
      extreme and of the urban-rural continuum. Whereas they occupy almost half of the
      land mass of the United States, they constitute only about 2 percent of the
      population. Exigencies of harsh climate and vast distances make the delivery of
      health and human services even more difficult than in other rural areas. This
      paper describes several innovative models for delivering mental health services
      to the persistently and seriously mentally ill in rural areas.

PMID- 10916316
TI  - The use of community surveys for health planning: the experience of 56 northwest
      rural communities.
AB  - A rural health services development program of the University of Washington
      School of Medicine has worked for 15 years with communities throughout the five
      state region of Alaska, Idaho, Montana, Washington and Wyoming to strengthen
      their health systems. In the course of that work, 56 communities were surveyed
      about their utilization and opinions of local health systems. This database
      allows the following generalizations to be made about rural Northwest
      communities: (1) People think highly of their local hospitals, physicians and
      other key components of the acute medical care system and want their hospitals to
      remain open. Older respondents are more satisfied than younger respondents; (2)
      the typical hospital market share is 36 percent, the typical physician market
      share is 50 percent (3) satisfaction with discrete, well-funded services such as
      pharmacy, ambulance and dentistry is quite high, whereas satisfaction with mental
      health and substance abuse treatment is significantly lower; (4) the most
      commonly cited serious problems in surveyed communities were "too few physicians
      or- services" and "care is too expensive"; and (5) there is great variation
      between communities in both satisfaction and utilization.

PMID- 10916318
TI  - A cinderella story.

PMID- 10916319
TI  - Restoring teeth.

PMID- 10916320
TI  - Amalgam bonding.

PMID- 10916321
TI  - Definition of myofascial face pain.

PMID- 10916322
TI  - Peer-review committees.

PMID- 10916323
TI  - Deceiving insurance companies.

PMID- 10916324
TI  - Cardiac valvulopathy.

PMID- 10916325
TI  - Dental practice value.

PMID- 10916326
TI  - Caring enough to change.

PMID- 10916327
TI  - The science and practice of caries prevention.
AB  - BACKGROUND AND OVERVIEW: Dental caries is a bacterially based disease. When it
      progresses, acid produced by bacterial action on dietary fermentable
      carbohydrates diffuses into the tooth and dissolves the carbonated hydroxyapatite
      mineral--a process called demineralization. Pathological factors including
      acidogenic bacteria (mutans streptococci and lactobacilli), salivary dysfunction,
      and dietary carbohydrates are related to caries progression. Protective factors-
      which include salivary calcium, phosphate and proteins, salivary flow, fluoride
      in saliva, and antibacterial components or agents--can balance, prevent or
      reverse dental caries. CONCLUSIONS: Caries progression or reversal is determined
      by the balance between protective and pathological factors. Fluoride, the key
      agent in battling caries, works primarily via topical mechanisms: inhibition of
      demineralization, enhancement of remineralization and inhibition of bacterial
      enzymes. CLINICAL IMPLICATIONS: Fluoride in drinking water and in fluoride
      containing products reduces caries via these topical mechanisms. Antibacterial
      therapy must be used to combat a high bacterial challenge. For practical caries
      management and prevention or reversal of dental caries, the sum of the preventive
      factors must outweigh the pathological factors.

PMID- 10916328
TI  - Permanent nerve involvement resulting from inferior alveolar nerve blocks.
AB  - BACKGROUND: This is a prospective study of patients referred to a tertiary care
      center with permanent alteration in sensation of the inferior alveolar nerves,
      lingual nerves or both that could have resulted only from an inferior alveolar
      nerve block. METHODS: Working with a subject pool of 83 patients, the researchers
      outlined and photographed the area of altered sensation on each patient, tested
      it with von Frey's hairs and two-point discrimination and tested temperature
      sensation and direction sense. RESULTS: Among a study population of 55 women and
      28 men with a mean age of 41.2 years, the lingual nerve was affected in 79
      percent of patients and the inferior alveolar nerve in 21 percent of patients. In
      47 patients, the causative inferior alveolar nerve block was painful when
      administered, but to the other 36 patients [corrected], it felt like a normal
      injection. Of the local anesthetic agents used, prilocaine was found to be more
      frequently linked to cases of nerve involvement in this study. DISCUSSION:
      Occasionally, an inferior alveolar nerve block can result in permanent
      involvement of the inferior alveolar nerve, lingual nerve or both. The incidence
      and exact mechanism of involvement still are unknown. By extrapolation from this
      study, an incidence of anywhere between 1:26,762 and 1:160,571 inferior alveolar
      nerve blocks can be surmised to result in this complication. A difference in
      referral rates for male and female patients is difficult to explain. The 34
      percent [corrected] incidence of dysesthesia in the patients in this study is of
      concern. CONCLUSION: Permanent nerve involvement after receiving an inferior
      alveolar nerve block is a documented but very rare complication of the inferior
      alveolar nerve block, and the exact mechanism involved is still unknown. CLINICAL
      IMPLICATIONS: Permanent nerve damage can very occasionally occur as a result of
      an inferior alveolar nerve block. The exact mechanism is unknown, and there is no
      means of prevention. Knowledge of the risks and complications of local anesthesia
      is essential.

PMID- 10916329
TI  - Maintaining mutans streptococci suppression with xylitol chewing gum.
AB  - BACKGROUND: One strategy for treating dental caries is to suppress oral mutans
      streptococci, or MS, with chlorhexidine, or CHX, mouthrinse. Oral MS levels,
      however, tend to quickly return to baseline values without further intervention.
      In this clinical study, the authors evaluated the effect of xylitol chewing gum
      on MS regrowth. METHODS: The authors selected 151 subjects with elevated oral MS
      levels (> or = 105 colony-forming units per milliliter, or CFU/mL, of paraffin
      stimulated saliva). Subjects rinsed with 0.12 percent CHX gluconate mouthrinse
      twice daily for 14 days. The authors then randomly assigned the subjects to one
      of three groups. Those in the test group (n = 51) chewed a commercial xylitol gum
      three times daily for a minimum of five minutes each time for three months. The
      placebo group subjects (n = 50) used a commercial sorbitol gum, and the control
      group subjects (n = 50) did not chew gum. The authors estimated MS load on the
      dentition using paraffin-stimulated saliva samples. The authors serially diluted
      the samples, plated them on selective media and incubated them anaerobically;
      they then enumerated the colonies under a stereomicroscope. RESULTS: MS levels
      were not significantly different between the three groups at baseline (mean log
      CFU/mL +/- standard deviation: 5.4 +/- 0.7, 5.4 +/- 0.8, 5.2 +/- 0.7,
      respectively) nor after CHX therapy (2.7 +/- 0.8, 3.1 +/- 1.1, 3.0 +/- 1.1,
      respectively). After three months of gum chewing, the test group subjects had
      significantly lower salivary MS levels (3.6 +/- 1.2) than did the placebo (4.7 +/
      1.2) or control (4.4 +/- 1.3) group subjects. CONCLUSIONS: Xylitol chewing gum
      appears to have the ability to prolong the effect of CHX therapy on oral MS.
      CLINICAL IMPLICATIONS: Maintaining long-term caries-pathogen suppression is
      feasible with currently available commercial products and can be expected to
      result in significant caries inhibition.

PMID- 10916330
TI  - The interdisciplinary approach to oral, facial and head pain.
AB  - BACKGROUND: Chronic oral, facial and head pain is a common clinical problem, and
      appropriate diagnosis and management are a challenge for health care
      professionals. Patients often will first seek the care of dentists because of the
      pain's localization in the oral cavity and surrounding structures. This article
      emphasizes the importance of establishing accurate diagnoses and conducting
      appropriate triage of the patient with complex orofacial pain. CASE DESCRIPTIONS:
      The authors present two case reports illustrating the complex nature of oral,
      facial and head pain, and the potential and actual pitfalls in management of this
      condition. These representative cases demonstrate how orofacial pain--which
      appears to be localized in the peripheral dental and oral structures--can have
      extremely complex etiologies involving other anatomical structures, the central
      nervous system and psychological factors. The reports point to the need for the
      expertise of a number of specialists in such cases. CLINICAL IMPLICATIONS: If the
      symptoms and clinical findings do not appear to be consistent with typical oral
      disease, or if standard treatments do not alleviate the pain, the dental
      clinician must consider other, more complex orofacial pain diagnoses. The dental
      professional should not hesitate to make referrals to key specialists or to
      members of an interdisciplinary team at a pain treatment center who have the
      expertise to appropriately diagnose and manage chronic oral, facial and head
      pain.

PMID- 10916332
TI  - Readability of published dental educational materials.
AB  - BACKGROUND: A growing number of adult Americans are functionally illiterate.
      These people often do not understand educational documents written by health care
      professionals, especially if English is the reader's second language. This
      problem has received little attention in dentistry. METHODS: In this study, the
      author selected a sampling of 24 patient educational documents from several
      dental resources and reviewed them for readability, using a computer-based
      program that assigns a reading level of understanding on the basis of a standard
      formula known as the Flesch-Kincaid Formula. The author also conducted a
      subjective review of each document to identify seemingly unnecessary professional
      jargon and words that were unlikely to be understood by many readers. RESULTS:
      Reading levels varied from third to 23rd grade (according to the Flesch-Kincaid
      Formula), and 41.7 percent of the materials were written at greater than the
      recommended level for understanding by most patients (mean level: seventh to
      ninth grade). Many dental specialty publications were written at or near college
      levels. Many documents had multiple grammatical errors. Seventy-nine words in the
      reviewed documents were considered to be jargon or potentially obscure to many
      lay readers. CONCLUSIONS: More attention needs to be focused on the preparation
      of written educational materials for dental patients, to make the documents more
      understandable to the average patient. Guidelines for acceptable writing are
      available in the medical, nursing and pharmaceutical literature.

PMID- 10916331
TI  - Cinnamon-induced oral erythema multiformelike sensitivity reaction.
AB  - BACKGROUND: Erythema multiforme, or EM, is a hypersensitivity reaction to agents
      such as herpes virus, drugs or foods. Oral EM-like reactions may be induced by
      cinnamon. It is important for dentists to recognize this condition. CASE
      DESCRIPTION: The authors report an unusual case of cinnamon-induced oral EM-like
      reaction in an older female patient. The disease manifested itself as chronic
      extensive surface ulcerations and lip swelling. The patient was treated
      repeatedly with topical and systemic steroids but responded to them only
      temporarily. The patient was cured when the offending agent--cinnamon--was
      eliminated from her diet. CLINICAL IMPLICATIONS: Oral EM or EM-like reactions
      pose a diagnostic dilemma due to their varied etiologies and clinical
      manifestations. Correct diagnosis is essential for effective treatment. A
      negative skin test does not rule out an allergic reaction to food.

PMID- 10916333
TI  - Using a modified subopaquing technique to treat highly discolored dentition.
AB  - BACKGROUND: The objective of esthetic dentistry is to treat diverse problems and
      achieve natural-appearing results. The author reviews the issues involved in the
      discoloration of human dentition and the concerns associated with current
      treatment for this problem. Understanding the proper use of materials in esthetic
      dentistry can result in a conservative, natural-appearing restoration. OVERVIEW:
      Dentition discoloration due to intrinsic staining can be a severe esthetic
      problem. Current treatment using crowns and highly opaque porcelain veneers has
      inherent disadvantages in regard to the final restorations. The author explores a
      subopaquing technique that allows for progressive lightening of highly stained
      teeth to create natural color depth in a conservative porcelain veneer procedure.
      CLINICAL IMPLICATIONS: In treating dental problems, the clinical practitioner
      looks for solutions that conserve tooth structure. To achieve natural-appearing
      esthetic results, it is important for the practitioner to be aware of
      technological advances in materials science as well as the proper use of esthetic
      dental techniques. Understanding the problems associated with dental
      discoloration and ways of correcting them will allow the practitioner to solve
      these moderate-to-severe esthetic problems on a consistent basis.

PMID- 10916334
TI  - Third-party reimbursement and use of fluoride varnish in adults among general
      dentists in Washington State.
AB  - BACKGROUND: Studies have indicated that a minority of dentists regularly use
      fluoride varnish to control caries. To increase the use of this new technology,
      Washington Dental Service, or WDS, began reimbursing dentists for providing
      fluoride varnish in January 1996. The aim of the authors' study was to determine
      whether reimbursement increased dentists' use of fluoride varnish. METHODS: In
      the fall of 1995, the authors asked a random sample of 532 general dentists in
      Washington state to complete a mail questionnaire on their use of caries control
      services. The survey was conducted before the institution of payment for fluoride
      varnish use, and dentists were unaware that fluoride varnish use would be a paid
      service in January 1996. In the fall of 1997 the same dentists were asked to
      complete a second questionnaire on the same topic. RESULTS: About 32 percent of
      dentists used fluoride varnish regularly before WDS started reimbursement for the
      service. Two years after reimbursement began, about 44 percent of dentists
      regularly used fluoride varnish (P = .004). Dentists' rates of use of other
      caries-control services (chlorhexidine rinses for caries control and adult pit
      and-fissure sealants) did not change. Dentists' reasons for not using fluoride
      varnish included lack of awareness, lack of convincing evidence of a favorable
      cost:benefit ratio, patients' rejection of the service and low caries risk among
      adult patients. CONCLUSIONS: After fluoride varnish became a covered benefit, the
      use of fluoride varnish among general dentists increased after two years, but a
      majority of dentists still had not adopted the technology. The increase in use
      may be due to reimbursement, as well as other factors. PRACTICE IMPLICATIONS:
      Reimbursement by itself cannot increase dentists' use of caries control services.

PMID- 10916335
TI  - Minimizing excessive composite resin when fabricating fiber-reinforced splints.

PMID- 10916336
TI  - The effect of denture adhesive on mandibular movement during chewing.
AB  - BACKGROUND: The authors conducted a study to determine if reducing mandibular
      denture movement through the use of a denture adhesive improves chewing function
      in edentulous patients. METHODS: The authors compared the mean chewing rates of
      10 denture wearers who used and did not use a denture adhesive with that of a
      control group of 10 dentate people. The authors recorded mandibular movements
      using a multichannel magnetometer tracking system while the subjects chewed
      standardized pieces of dried apricots and fresh white bread. They made recordings
      for the test subjects without the use of denture adhesive and at zero, two and
      four hours after Fixodent denture adhesive cream (Procter & Gamble Co.) was
      applied to the mandibular denture. RESULTS: The mean chewing rate for the control
      group was significantly faster than that of the test group at baseline (P < .01).
      The authors found statistically significant increases in the mean chewing rates
      for the test group after the denture adhesive was applied at all time points for
      both foods. None of the after--adhesive-application rates were significantly
      different from the control group's rate (P > .05). CONCLUSIONS: Use of denture
      adhesive increased the mean chewing rate in test subjects immediately after and
      at two and four hours after denture adhesive was applied to a rate that
      approximated that observed in control subjects (P > .05). CLINICAL IMPLICATIONS:
      These findings show that using a denture adhesive promotes a faster and more
      natural rate of chewing.

PMID- 10916337
TI  - Curing restorative resin: a significant controversy.

PMID- 10916338
TI  - A personal change and a changing panorama: looking toward the next decade.

PMID- 10916339
TI  - Holding HMOs accountable. Court rules that HMOs can be held liable for
      negligence.

PMID- 10916340
TI  - [A trial of infection control measure by clinical microbiology laboratory].
AB  - In 1998, we developed a Total Infection Control System in Saga Medical School
      Hospital, and would like to introduce it for the practical use. This system was
      named "Dr. FLEMING" (Flexible Microbiological Test & Information System for the
      New Generation) and is expected to help physicians by providing highly valuable
      test results and useful information. For example, bacterial identification and
      drug susceptibility test can be completed within 4-6 hrs after bacterial colony
      is isolated, and the test report the contains full-colored pictures to enhance
      understanding. In addition, we have made an information center for infectious
      disease, where physicians can have access to various data bases outside our
      hospital. Furthermore, we offer many kinds of useful information to physicians
      working at other medical facilities to assist their clinical practice of
      infectious diseases.

PMID- 10916341
TI  - [Prevalence of hemolytic streptococcal infection in Kitakyushu: incidence and
      characteristics of isolates (1994-1997)].
AB  - In the study of prevalence of hemolytic streptococci in Kitakyushu-city from 1994
      to 1997, both seasonal variation of the number of group A hemolytic streptococci
      isolates and their age distribution fitted in well with the cases of
      streptococcal infection which is monitored in the Japanese infectious disease
      surveillance system. Dominant serotypes of group A hemolytic streptococci in
      Kitakyushu-city were T-12 and T-3 from 1994 to 1995, T-28 and T-12 in 1996, T-2
      and T-4 in 1997. Compared with prevalent serotypes of group A hemolytic
      streptococci in the City and those in Japan, the geographically close relation
      was observed. The epidemic serotypes in the City tended to fall behind those in
      Honshu, the main land of Japan. Most of the isolates were resistant to kanamycin
      (KM). Few isolates were resistant to other drugs except tetracycline (TC), to
      which 14% of the isolates were resistant. Strains of multiple-drug resistant were
      less than 5%. Gene of speB was detected in all group A strains by PCR method, and
      a close relationship was observed between T-type and SPE gene type.

PMID- 10916342
TI  - Outbreak of cryptosporidiosis after contamination of the public water supply in
      Saitama Prefecture, Japan, in 1996.
AB  - An outbreak of cryptosporidiosis occurred in Ogose Town, Saitama Prefecture.
      Japan, in June 1996. Of 12,345 respondents to a questionnaire sent to households
      in the town (population; 13,809), 8,812 (71.4%) reported an acute
      gastrointestinal illness some time between May and July. In addition, 274
      traceable visitors at local inns, golf courses, and the like during this period
      and 54 employees from out of town were infected. Cases of cryptosporidiosis were
      estimated to 9,140. Of these, 2,856 subjects were treated at outpatient clinics
      and 24 subjects were hospitalized (some subjects counted twice). No deaths were
      attributed to the outbreak. Among the visitors to Ogose who were traced, 7
      persons who stayed only one day during the outbreak and drank half a glass to 2
      glasses (100 to 360 ml) of tap water had cryptosporidiosis confirmed by
      laboratory tests. The median incubation period for the 14 persons for whom this
      calculation was possible was 6.4 days (range, 5 to 8 days). Of 469 pupils
      reporting details of their fever and diarrhea, abdominal cramps, or these
      combined signs and symptoms, the median maximum body temperature was 37.8 degrees
      C (range, 36.7 to 40.3 degrees C). The duration of illness, reported by 608 of
      the pupils, was 5.2 days (range, 1 to 15 days), and that reported by 187
      employees was 4.8 days (range, 1 to 18 days). The longest known time for
      discharge of oocysts after onset was 44 days. Blood was not found in the 609
      stool specimens examined. The outbreak was caused by contamination of the town's
      potable water by Cryptosporidium parvum oocysts. The town's water treatment plant
      treated river water by coagulation, sedimentation, sand filtration, and
      chlorination. Contamination arose because of various natural and artificial
      factors: one was that the monthly precipitation in May was much lower than
      average, causing the river water level to drop. Another factor was heavy rainfall
      one night in May that increased water turbidity. The amounts of the coagulant
      added seemed to be insufficient. There are two inns, three public lavatories, and
      two small-scale wastewater treatment plants upstream 400 m and 1,200 m of the
      intake point of the town's water treatment plant. However, there are no farms
      with livestock in the area. We suggest that the location of the water treatment
      facilities was inappropriate, and that oocysts had circulated from the potable
      water to humans to sewage to the river and back to the potable water.

PMID- 10916343
TI  - [Evaluation of enrichment cultures for detection of Escherichia coli O157 from
      human stool specimens by using immunomagnetic separation].
AB  - We investigated the conditions of enrichment cultures preceding the
      immunomagnetic separation (IMS) procedure to detect Escherichia coli O157 (E.
      coli O157) from human stool specimens in routine laboratory examinations. Samples
      were made by adding either of the three selected strains of E. coli O157 to
      stools from three healthy human subjects in three different doses. The enrichment
      cultures were done for 18 hours at 37 degrees C or 42 degrees C, using five
      different media such as trypticase soy broth (TSB). TSB containing cefixime,
      tellurite and vancomycin, modified EC broth (mEC), mEC containing novobiocin (N
      mEC) and BGLB. The IMS procedure following enrichment culture increased the
      detection rate of E. coli O157, irrespective of the kinds of the media and the
      temperatures. It recovered E. coli O157 in 42 samples out of 90, while only 31
      samples were positive when the IMS was not applied. The N-mEC showed the best
      recovery rate of the five enrichment media, and it was the only media that
      recovered the E. coli O157 Gunmma 298 strains at a level of 2-3 cells per ml. In
      73 stool samples collected from probable patients with E. coli O157 infection and
      subjects who made close contact with the patients, positive results were obtained
      in six samples with the N-mEC enrichment followed by the IMS procedure, while
      only three samples were positive by the direct isolation culture. It was
      concluded, therefore, that, in routine laboratory examinations of E. coli O157
      from human stools, the N-mEC enrichment culture for 18 hours followed by the IMS
      procedure is a sensitive method even when the dose of E. coli O157 in the stool
      is minimal.

PMID- 10916344
TI  - [Aspergillosis with non-cavitary lung cancer].
AB  - Growth of Aspergillus was observed in the necrotic tissue of non-cavitary lung
      cancer. Case 1 was a 60-year-old male complaining of cough and fever and was
      found to have left lower lobe atelectasis on chest X-ray. Bronchoscopic
      examination showed the yellow soft lesion occluding the left upper and lower lobe
      bronchus. Specimen from the lesion demonstrated adenocarcinoma and hyphae of
      Aspergillus in the necrotic tumor. Case 2 was a 53-year-old male who was found to
      have a left upper lobe mass by chest X-ray screening. Bronchoscopic examination
      showed the yellow polypoid lesion occluding the left upper division bronchus.
      Pneumonectomy was done and resected specimen of the lesion demonstrated
      adenocarcinoma and the hyphae of Aspergillus growing in both necrotic tissue and
      cancer tissue. As both patients had hyphae of Aspergillus in the necrotic tumor,
      it is considered that the presence of necrosis may cause the growth of
      Aspergillus.

PMID- 10916345
TI  - [Three cases of tuberculosis complicating acute respiratory distress syndrome].
AB  - In this report, we describe three patients with pulmonary tuberculosis with acute
      respiratory failure with an extensive tuberculous consolidation in bilateral lung
      fields. Disseminated intravascular coagulation (DIC) was present in one patient
      and miliary tuberculosis in two patients. They all developed acute respiratory
      distress syndrome (ARDS), nessecitating management by mechanical ventilation with
      a combination therapy of antituberculous agents and methylprednisolone (m-PSL)
      pulse therapy. Only one patient survived in whom the PaO2/FiO2 ratio recovered
      rapidly after the initiation of therapy. Two patients whose systemic condition
      upon admission was critically ill eventually died of hepatic failure and
      bacterial pneumonia, even though ARDS and pulmonary tuberculosis were
      successfully treated. Prognosis of pulmonary tuberculosis complicating ARDS and
      DIC is poor, and these patients need systemic intensive treatment, in which m-PSL
      therapy may be beneficial.

PMID- 10916346
TI  - [A case report of pneumococcal pneumonia diagnosed by urinary antigen].
AB  - Using a kit for the rapid detection of Streptococcus pneumoniae, we examined 3
      clinical cases, clearly diagnosed as pneumococcal pneumonia. Case 1 was a 63-year
      old man hospitalized for right middle lobular pneumonia. Streptococcus pneumoniae
      was detected by blood culture initiated on the day of admission. His urine sample
      was found to have Streptococcus pneumoniae antigen at hospital day 4, and
      positive test results were observed 3 times thereafter. The other 2 cases had
      negative sputum and blood cultures, but they were positive for urine antigen,
      with clinical courses consistent with those of pneumococcal pneumonia. The kit
      used was determined to provide a test result within 15 min for each urine sample,
      and it was easy to perform. Thus, this kit is expected to serve as a very useful
      clinical tool.

PMID- 10916347
TI  - [A case of amebic colitis cured with multiple cicatricial strictures].
AB  - A 53-year-old male was admitted to Gifu Red Cross Hospital with the complaints of
      diarrhea, abdominal pain, and fever. He had a temperature of 38.4 degrees C and
      diffuse abdominal tenderness without guarding or rebound. Plain film of the
      abdomen showed marked dilatation of the transverse colon. Sigmoidoscopy showed
      multiple aphthoid erosions and pseudomorphic ulcers, and mucosal biopsies
      demonstrated numerous trophozoites of Entamoeba histolytica. The patient was
      treated with oral metronidazole with rapid improvement. Barium enema and
      colonoscopy after improvement showed multiple cicatricial strictures. Although
      prompt diagnosis and therapy prevented fulminant changes, the patient was cured
      with multiple cicatricial strictures, a rare complication of amebic colitis. It
      is important to keep in mind severe amebic colitis in the differential diagnosis
      of patients with diarrhea and high fever.

PMID- 10916348
TI  - [Comparison of the results of laparoscopic cholecystectomy preformed in the usual
      way and with a lesser number of trocars].
AB  - Laparoscopic surgery is a part of the minimally invasive surgery. Its aim is to
      make on operation as valuable as the open one, or even more, with a smaller
      invasion or injury of the body. With the instruments improvement the operation
      would be possible without any remarkable organism injury. On the other hand,
      modifications of the operation techniques lead to progress. European technique of
      laparoscopic cholecystectomy using four trocars has changed. Procedures are
      performed with one trocar less. Two groups of two hundred patients each have
      undergone laparoscopic cholecystectomy. The operation in the first group was
      performed using four, and in the second group using three trocars. The aim of the
      investigation was to compare these two methods of laparoscopic cholecystectomy.
      The results analysis showed that laparoscopic cholecystectomy using three trocars
      did not cause either a higher complication rate, prolonged average operation time
      or longer duration of hospitalisation. The analgesics consumption was lower, sick
      leaves were shorter, with smaller total costs, and cosmetic effect was better.

PMID- 10916349
TI  - [Levels of serum alpha-fetoprotein before and after transcatheter embolization of
      hepatocellular tumors with Lipiodol].
AB  - Hepatocellular cancer is a common cancer in Africa and Asia, while slight
      increase has been recorded in Europe and USA during the last decade. In selected
      patients embolization with administration of Lipiodol and anticancer drugs can be
      used to reduce tumour mass. In this work the values of serum alpha-fetoprotein
      (AFP) before, immediately after, and 7 and 30 days after embolization were
      analyzed in 20 patients with hepatocellular cancer. Values of AFP immediately
      after embolization were the same as before embolization, while 7 and 30 days
      later they were significantly lower (p < 0.05). In all patients values of AFP
      were higher 30 days after embolization compared to 7 days after embolization.
      Monitoring of serum AFP could be used as a complementary method with radiologic
      imaging methods in patients embolized for hepatocellular cancer.

PMID- 10916350
TI  - [Effect of broad spectrum beta-lactamases on in vitro sensitivity of clinical
      isolates of Klebsiella pneumoniae to oral cephalosporins].
AB  - Extended-spectrum beta-lactamases which confer resistance to oxymino
      cephalosporins, are derived from common TEM-1, TEM-2 and SHV-1. beta-lactamases
      by mutations which alter the configuration of active site and expand their
      spectrum of activity. The aim of this investigations was to determine the effect
      of these enzymes on in vitro susceptibility of clinical isolates of Klebsiella
      pneumoniae to oral cephalosporins. beta-lactamases were characterised by
      isoelectric focusing and polymerase chain reaction. The susceptibility of K.
      pneumoniae isolates harboring these enzymes to oral cephalosporins was determined
      by broth-microdilution method and the stability of these antibiotics to enzyme
      degradation was tested by macroiodometric method. Based on the isoelectric point
      beta-lactamases were assigned into three groups: SHV-2 type (pI 7.6), SHV-5 type
      (pI 8.2) and TEM-1 derivates (pI 5.4). All types of beta-lactamases described in
      this investigation were associated with high level of resistance to older
      cephalosporins like cephalexin, cefaclor, cefuroxime, cefotiam, cefprozil and
      cefadroxil and to amoxycillin too. Third generation oral cephalosporins like
      ceftibuten and cefetamet were more stable in the presence of beta-lactamases but
      some of the strains were resistant to these antibiotics too. SHV-5 beta
      lactamases producers displayed higher level of resistance to most of oral
      cephalosporins compared to SHV-2 and TEM producing strains. According to the
      results of this investigation oral cephalosporins cannot be considered as a
      therapeutic option for the treatment of infections caused by ESBL producing K.
      pneumoniae isolates.

PMID- 10916351
TI  - [Gene therapy of tumors of the head and neck: clinical use of the p53 tumor
      suppressor gene].
AB  - Gene therapy involves the introduction of genetic material (DNA) in patient
      cells, in order to produce therapeutic effect after expression of the new gene.
      New insights in head and neck tumor etiology and the development of genetic
      engineering techniques made the gene transfer a reality. This article gives a
      brief overview of investigations leading to clinical application of gene therapy
      in head and neck tumors. A good therapeutic response in more than 50% patients
      has been reported in literature. These results and future potential of gene
      therapy are discussed.

PMID- 10916352
TI  - [Specificity of diagnostic procedures in occupational diseases].
AB  - Characteristics and specificities of diagnostic procedures as a basis of
      diagnosis of occupational diseases are explained. The aforementioned include
      working history, clinical, laboratory and functional tests and evaluation of
      working environment. Examples of practical application of such procedures are
      listed.

PMID- 10916353
TI  - [Mechanisms of renal retention of sodium and water in heart failure, cirrhosis
      and pregnancy].
AB  - A decade after a unifying hypothesis of sodium and water regulation had been
      proposed, evidence has accumulated in support of common (patho)physiologic
      mechanisms of sodium and water retention in congestive heart failure, cirrhosis
      and pregnancy. Either primary arterial vasodilatation (cirrhosis, pregnancy), or
      a decrease in cardiac output (low-output heart failure) impair arterial
      circulatory integrity ("effective arterial blood volume"), which unloads
      ventricular and arterial baroreceptors. Consequently, activation of the
      sympathetic nervous system, renin-angiotensin-aldosterone system, arginine
      vasopressin, as well as other less well explored mechanisms occurs in an attempt
      to restore the arterial circulatory integrity. Consequences of this neurohumoral
      activation with arterial uderfilling include renal sodium and water retention and
      an increase in peripheral vascular resistance. In this review specific
      pathophysiologic mechanisms underlying the sodium and water retention in
      congestive heart failure, cirrhosis and pregnancy will be discussed.

PMID- 10916354
TI  - [Acute psychosis with aggressive behavior as a consequence of MDMA (Ecstasy)
      consumption].
AB  - Presented is a case of acute paranoid psychosis in a patient who took MDMA
      (Ecstasy), became violent and was prosecuted by law. After the repeated intake of
      MDMA, the second psychotic episode occurred, or maybe even several episodes
      (about which we have no data). The patient reacted well and fast to the therapy
      was normal. Those who had psychotic reactions after taking MDMA have a great
      chance to react in the same way when taking the drug again. Other authors present
      similar observations. This article is aimed to warn our expert population to
      seemingly approaching greater wave of Ecstasy drug, as well as to point to its
      consequences and treatment.

PMID- 10916355
TI  - [Hypertensive crisis caused by metoclopramide].
AB  - Metoclopramide is a dopamine-receptor antagonist which stimulates the upper
      gastrointestinal tract motility. It is often used in the management of some forms
      of nausea and vomiting. Hypertensive crisis which occurred in a 76-year-old man
      who had received metoclopramide 30 mg daily is reported.

PMID- 10916356
TI  - [Ether and chloroform narcosis in the pages of Zagreb newspapers from 1847 to
      1849].
AB  - Overviews of the development of anesthesiology in Croatia always emphasize that
      the first report on the employment of ether anesthesia was published on March 13,
      1847, in the Zadar newspaper Gazzeta di Zara. In the world as well, daily
      newspapers played an important part in spreading the news about the discovery and
      first use of ether anesthesia. This fact stimulated us to do a systematic search
      through Zagreb press of that time. Agramer Zeitung (Zagrebacke novine), with its
      supplement Luna--Beiblatt zur Agramer politischen Zeitung, then Narodne novine
      and Sudslavische Zeitung (Slavenski jug), were examined for the period from 1846
      to the beginning of 1849. Research was directed to give the following answers:
      when the first writings about discovery and surgery in ether and chloroform
      anesthesia appeared, which primary and secondary sources of information were
      used; who wrote them; what kind of attitudes and opinions were promoted, and
      whose; and finally, did Zagreb newspapers communicate or record the news about
      first employment of ether and chloroform anesthesia in surgery in Croatia.
      Research results reveal that Zagreb press had an important role in informing
      Croatian public about breakthroughs and first experiences in the use of ether and
      chloroform anesthesia in Europe, and that it contributed to their popularization
      and employment in our settings. From January 26, 1847, Zagreb papers began
      publishing first articles about surgeries in ether anesthesia, referring to
      successes achieved in England and Scotland, and later in Vienna, Berlin, Prague
      and other big European towns. However, there were no reviews on first successes
      in America. Sources of information were mainly foreign daily papers, mostly
      Austrian, and much less often European professional medical journals. Zagreb
      papers did not report on first surgeries performed in Zadar, Dubrovnik and Split
      during 1847. The only news from the country referred to the procedure performed
      in August 1847 in Sisak. This is the first known published information about the
      beginnings of ether anesthesia in northwest Croatia. The article was written by
      an A. C., who witnessed and described first experiments using ether anesthesia in
      a Vienna clinic. Compared to the number of writings on ether anesthesia,
      introduction of chloroform received much less attention. The first news on
      Simpson's success was published on December 11, 1847. Regarding total number of
      texts dedicated to the topic of painless surgery, culmination was reached in
      1847, and afterwards the interest of press in this field decreased. In the period
      from 1847 to the beginning of 1849, not one article was followed by subsequent
      comments of Croatian readers, either lay people or medical practitioners. Texts
      were not written sensationally, but with the aim to objectively inform the public
      by communicating experience and attitudes of contemporary reputable surgeons,
      including all professional details which might be useful for potential users-
      patients, as well as for Croatian physicians, surgeons, obstetricians, dentists
      and veterinarians.

PMID- 10916357
TI  - [Treatment of diabetic foot with hyperbaric oxygenation].

PMID- 10916358
TI  - The ADA mediation guidelines: providing direction in an emerging field.

PMID- 10916359
TI  - Dental caries and the microbial ecology of dental plaque: a review of recent
      advances.
AB  - Our understanding of the microbial ecology of dental plaque has rapidly grown
      with recent developments in the techniques of molecular biology. In particular,
      knowledge of the mechanisms underlying the acquisition, establishment,
      pathogenicity, and evolution of the group of organisms responsible for dental
      caries--the mutans streptococci--has expanded to the point that we can now
      contemplate new opportunities for caries prevention. These advances reinforce
      developing concepts of dental plaque as an interdependent, interacting community
      of specialised organisms with an ability to rapidly adapt conferred by gene
      structures that facilitate the expeditious modular rearrangement of protein
      components.

PMID- 10916361
TI  - The Postgraduate Diploma in Clinical Dental Technology.
AB  - The Dental Act 1988 included requirements for the registration of clinical dental
      technicians, a new category of dental health worker. Despite the Act containing
      provision for a course of training in clinical dental technology, 11 years
      elapsed before the first candidates would graduate in this discipline. This paper
      describes the development and implementation of the new Postgraduate Diploma in
      Clinical Dental Technology, PGDipCDTech(Otago). Diplomates of the inaugural
      course in 1999 were the first students, other than students of dentistry, to
      obtain a clinical qualification from the School of Dentistry. Overall the course
      was very successful, but the provisions of the Dental Act inhibit flexible
      approaches to the teaching of clinical dental technology.

PMID- 10916362
TI  - The great auricular nerve: a case report and review of anatomy.
AB  - This report reviews the pertinent anatomy of the great auricular nerve. The
      clinical significance of this nerve is apparent in some patients undergoing lower
      third molar surgery under local anaesthesia. The great auricular nerve arises
      from the cervical plexus and overlaps territory from the trigeminal nerve
      supplying sensory innervation to the angle of the mandible. In certain instances,
      a separate infiltration may be needed to achieve total analgesia of the region.

PMID- 10916360
TI  - Analyses of treatment outcomes for complete dentures provided in an undergraduate
      teaching programme.
AB  - Identifying the source of difficulties some patients experience after replacement
      dentures are made is an essential part of improving quality care should further
      treatment to assist the patient be considered necessary. This report examines the
      findings of a retrospective review of 181 patients' records following the
      provision of complete dentures by undergraduate dental students at the University
      of Otago School of Dentistry. Treatment was provided in 1998; the audit commenced
      in August 1999 to allow sufficient time for the records to include review
      appointments. Forty-eight patients (26.5 percent) were recommended to receive
      further replacement dentures to correct errors identified by the supervising
      clinician. Causation was broadly attributed to dissimilarities from patients'
      previous dentures (42 percent), occlusal factors (33 percent), and difficulties
      in establishing a functional denture-bearing area (11 percent). These findings
      were compared with a published analysis of denture faults identified during the
      clinical examination of patients referred to a specialist in dental prosthetics.
      Evidence suggests that the use of a clinical technique which incorporates
      information from previously successful dentures may be appropriate in the
      construction of replacement dentures.

PMID- 10916363
TI  - The jaw-winking syndrome.
AB  - The jaw-winking syndrome involves synkinesis of the pterygoid muscles and levator
      palpebrae superioris, where the eyelid retracts with mandibular movements. Its
      appearance in the adult may be associated with other pathology, and recognition
      in the neonate may allow for earlier recognition of any ophthalmological
      problems. As it is elicited by jaw movements, the oral health care provider may
      be the first to recognise the condition. This report describes the incidental
      finding of jaw-winking syndrome in a 22-year-old Asian man. Although he suffered
      no physical or psychological effects from the condition, he did have an
      associated, corrected, ophthalmological defect.

PMID- 10916365
TI  - Review of pain study of aspirin, ibuprofen and paracetamol

PMID- 10916364
TI  - Leukaemia in children. Part I: Orofacial complications and side-effects of
      treatment.
AB  - Significant orofacial complications of leukaemia in children include
      lymphadenopathy, spontaneous gingival bleeding, labial and lingual ecchymoses and
      mucosal petechiae, ulceration, gingival swelling, and infections. The dentist may
      be the first to notice signs of the illness. Treatment of leukaemia can result in
      serious orofacial problems which include oral mucositis and ulceration,
      infections, spontaneous gingival bleeding, neuropathy, xerostomia, and gingival
      hypertrophy. A prompt diagnosis leading to early intervention can decrease the
      morbidity and mortality of the disease and its treatment.

PMID- 10916366
TI  - A little less heat, a little more light.

PMID- 10916367
TI  - [Depression of serum pyridoxal levels in theophylline-related seizures].
AB  - In order to study whether a theophylline-related seizure is caused by a decrease
      in serum vitamin B6, serum pyridoxal (PAL) levels were measured in children with
      bronchial asthma treated with theophylline. The serum PAL levels of asthmatic
      children (n = 31) treated with theophylline were significantly lower than those
      of control subjects (n = 21). Moreover, we evaluated PAL levels in four subjects
      within twenty-four hours after a seizure with or without fever. The level was low
      in three of the four. These results suggest that the decrease in PAL levels
      caused by theophylline may lower the seizure threshold.

PMID- 10916368
TI  - [Clinical spectrum and management of holoprosencephaly].
AB  - To study the phenotypic spectrum and management of holoprosencephaly (HPE), we
      reviewed the findings of eight children with HPE from 3 to 10 years of age, who
      underwent intervention programs and rehabilitation at our center. One patient had
      alobar HPE, three semilobar HPE, and four lobar HPE. All patients had postnatal
      growth retardation, and seven showed a decreased BMI (< 25% tile). All patients
      had severe developmental delay and mental retardation (DQ < 40), showing no
      obvious correlation between their severity and the type of HPE. Neurologically
      seven patients had spasticity (3 spastic quadriplegia, 2 spastic diplegia, 2
      mixed-type), except one patient with a 7q deletion [46,XY,del(7) (q35)] who had
      generalized hypotonia. Seven had variable types of seizures. All patients had
      feeding difficulties and were assessed by speech-language therapists. Four
      patients required tube feeding, four had gastroesophageal reflux disease.
      Recurrent respiratory tract infection was common. Three patients had abnormal
      serum sodium concentration (1 diabetes insipidus, 1 idiopathic hypernatremia, 1
      hyponatremia). No family history of HPE was elicited. In conclusion, patients
      with HPE should be followed up closely for complications such as feeding
      difficulty, malnutrition, seizures, spasticity, infection, and osmoreceptor
      hypothalamus-hypophyseal axis abnormalities.

PMID- 10916369
TI  - [Medical, educational, and social supports required by parents of persons with LD
      and related conditions].
AB  - The authors surveyed handicaps in daily life of persons with learning disability
      (LD) or its related conditions. Among 470 parents of persons with LD, 266 (56.6%)
      responded. The required assistance differed according to the age and handicaps.
      Whereas 18.0% of the respondents were utilizing current social services, 75.3%
      agreed on the establishment of special welfare for LD. Social supports,
      comprehending medicine, education, occupation, and law are needed.

PMID- 10916370
TI  - [A patient with epilepsy, congenital alopecia and mental retardation: combination
      of atypical absence in waking and nocturnal partial seizure].
AB  - We report a 7-year-old girl with epilepsy, congenital alopecia, and mental
      retardation. She was hairless at birth. Very scanty hair, eyebrows and eyelashes
      appeared at 2 years of age. Developmental delay was first recognized at 6 years.
      Nocturnal partial seizures occurred at 4 years, and atypical absence in waking at
      6 years. Electroencephalogram showed spike-waves in the centrotemporal area which
      increased and developed into a generalized continuous spike and wave complexes
      upon sleeping at the age of 7 years 1 month. Ictal electroencephalogram in
      atypical absence showed generalized 3 c/s spike and wave complexes. Skin biopsy
      of the scalp showed scanty, immature hair follicles and immature sebaceous
      glands. Whether this case is related to ectodermal dysplasia is unclear.

PMID- 10916371
TI  - [Effects of mild hypothermia and steroid pulse combination therapy on acute
      encephalopathy associated with influenza virus infection: report of two cases].
AB  - We treated two children with influenza-associated acute encephalopathy by a
      combination of mild hypothermia and steroid pulse therapy. Case 1, a 2-year-and-3
      month-old boy, admitted to our hospital 7 days after the onset of central nervous
      symptoms. The brain MRI-CT revealed laminar cortical necrosis and severe brain
      edema. EEG showed very low voltage. Brain edema improved by the combination
      therapy. He had sequelae, but was able to eat. Case 2, a 1-year-and-10-month-old
      boy, admitted to our hospital 5 days after the onset of central nervous symptoms.
      Brain MRI showed frontal dominant cortical edema. EEG showed high voltage delta
      bursts. The combination therapy was effective, but he remained mental
      handicapped. The outcome was better compared to our previous cases of acute
      encephalopathy. The combination therapy is intended to counteract cytokines, and
      was considered to be an effective treatment against acute encephalopathy
      associated with an influenza virus infection.

PMID- 10916372
TI  - [Transient enlargement and spontaneous regression of interhemispheric cysts--a
      case report].
AB  - We report a 5-year-old male patient with interhemispheric cysts which showed
      spontaneous reduction in size. The patient was consulted to our hospital at 2
      days of life for the evaluation of intracranial cysts found by fetal
      ultrasonography. Magnetic resonance imaging (MRI) on admission disclosed multiple
      cysts in the interhemispheric region and agenesis of the corpus callosum. MRI
      performed later disclosed the association of pachygyria and heterotopia. On
      follow-up MRIs, the cysts peaked in size at 5 month of age and gradually reduced
      thereafter. He showed transient hypertonia but had neither neurological deficits
      nor signs of increased intracranial pressure except transient hypertonia
      throughout the course. The present case is the first with interhemispheric cysts
      showing spontaneous reduction in size. While the present case suggested that an
      interhemispheric cyst dose not necessarily need a surgical treatment, and that it
      is difficult to determine surgical indication based on clinical manifestations.

PMID- 10916373
TI  - [A case with mild subdural hematoma presenting with a transient cluster of
      convulsions--problems concerning differentiation from benign infantile convulsion
      and benign complex partial epilepsies in infancy].
AB  - A 1-month-old girl showed frequent partial seizures of sudden onset. Continuous
      spikes were observed in left central area during the ictal period, although
      interictal EEG showed neither epileptiform discharges nor focal signs. Optimal
      seizures control was obtained with intravenous administration of diazepam and
      subsequent oral administration of phenobarbital. She showed neither abnormal
      physical and neurological signs after seizures nor sequelae. CT examination on
      two days after the onset of seizures showed no obvious abnormal high density
      area. However, MRI examination on 10 days after the onset showed subdural
      hematoma in the left front-temporal area and right occipital area. Except for MRI
      findings, this case may be diagnosed as benign infantile convulsion or benign
      complex partial epilepsies in infancy. This case suggested that serial
      neuroradiological examinations were recommended for prospective studies about
      benign infantile convulsion and benign complex partial epilepsies in infancy.

PMID- 10916374
TI  - [Juvenile ischemic type of moyamoya disease: a case report].
AB  - Moyamoya disease is a rare, chronic cerebrovascular disorder characterized by
      progressive stenosis of the arteries composing the circle of Willis. The ischemic
      type of Moyamoya disease progresses insidiously. To prevent irreversible cerebral
      damage and psychomotor deterioration, early surgical treatment is considered
      indispensable. The patient may present with nonspecific symptoms and no specific
      abnormalities on brain MRI, and might be erroneously suspected as having
      psychosomatic disorder. The disease must be diagnosed as early as possible.
      Electroencephalography (EEG) is of little value in the diagnosis of the juvenile
      type of Moyamoya disease, except for the demonstration of "re-build up" after
      hyperventilation. Half of the children with Moyamoya disease have been
      demonstrated to exhibit "re-build up" after hyperventilation. Our patient showed
      normal background activities, no spike discharges and no slowing during
      hyperventilation. Nonetheless, we emphasize the appearance of irregular high
      voltage slow waves de novo after hyperventilation. The findings may be
      potentially useful for the screening of patients with the juvenile type of
      Moyamoya disease.

PMID- 10916375
TI  - [A case with congenital hydrocephaly and west syndrome who recovered from
      hypsarrhythmia after the resolution of shunt trouble].
AB  - Hydrocephalus occasionally causes West syndrome, but the mechanism is unknown. We
      experienced a case with West syndrome and congenital hydrocephaly, in which the
      EEG findings improved after the resolution of shunt complications. The course of
      this case implied the pathogenesis of West syndrome associated with congenital
      hydrocephaly, as well as the origin of the seizures and that of the EEG findings
      in West syndrome. A 7-month-old girl had congenital hydrocephaly. A prenatal
      diagnosis was made by ultrasonography, and ventricle-peritoneal shunting was
      performed 7 days after birth. During the following 7 months several shunt
      replacements were done because of recurrent shunt complications. Her first series
      of infantile spasms began at the age of 6 months, and treatment was started under
      the diagnosis of West syndrome. One month later, her seizures were controlled by
      pyridoxal phosphate, while the EEG still showed hypsarrythmia. Her shunt was then
      removed again, because of bacterial meningitis due to shunt infection. The
      recovery from shunt complication resulted in marked improvement of the
      hypsarrhythmia. Our experience and previous literature suggest the involvement of
      cerebral cortex in the occurrence of West syndrome associated with congenital
      hydrocephaly.

PMID- 10916376
TI  - [Two sibling patients with non-Fukuyama type congenital muscular dystrophy with
      low serum selenium levels--therapeutic effects of oral selenium administration].
AB  - We report a pair of siblings with non-Fukuyama type, merosin-positive congenital
      muscular dystrophy, born to unrelated parents. Patient 1 was a 16-year-old girl
      with myopathy, cardiomyopathy, severe mental retardation and epilepsy. Patient 2
      was a younger brother of patient 1, a 10-year-old boy with myopathy, severe
      mental retardation and epilepsy. Their serum selenium levels were decreased to 25
      micrograms/l and 55 micrograms/l, respectively (normal 97-147 micrograms/l).
      Their muscle biopsy findings were similar to those seen in selenium deficient
      myopathy, showing abnormal mitochondrial distribution and giant mitochondria.
      After oral administration of selenium for 3 months, their gait disturbance
      apparently improved, which was confirmed by a gait analysis system. Why their
      gait improved remain unclear, but a defect in selenium metabolism may play a role
      in the development of congenital muscular dystrophy and mental retardation.

PMID- 10916378
TI  - [Recurrent tongue biting due to hypnic myoclonia in infancy].
AB  - We report a 15-month-old female infant who had recurrent tongue biting due to
      hypnic myoclonia. She began to bite her tongue and bleed when she was 9 months
      old. The tongue biting was accompanied by generalized myoclonus and was seen only
      during drowsiness. On admission at 15 months of age, she was observed by video
      EEG monitoring. There were hypnic jerks with powerful closure of the mouth and
      severe screaming, but no accompanying evidence of epileptic discharges. The
      tongue biting with hypnic myoclonia disappeared spontaneously at 22 months of
      age, and was considered to be an age-dependent phenomenon related to the
      maturation of the brain and to the development of oral functions.

PMID- 10916377
TI  - [Improvement of obstructive sleep apnea by uvulopalatopharyngoplasty and
      tonsillectomy in a case of Duchenne muscular dystrophy].
AB  - A 10-year-old boy with Duchenne muscular dystrophy (DMD) underwent
      uvulopalatopharyngoplasty and tonsillectomy for obstructive sleep apnea (OSA). He
      has snored loudly during nocturnal sleep since infancy, and OSA developed one and
      a half years after he was wheel chair-bound at 8 years. Magnetic resonance
      imaging (MRI), conventional spirometry and overnight polysomnography were
      performed before and after the surgery. MRI before surgery revealed moderate
      tonsillar hypertrophy and a long uvula which narrowed the upper airway. After the
      surgery, his vital capacity (VC) was not changed (% VC; from 77 to 78%), but
      forced expiratory volume (FEV) was improved (FEV 1.0%; from 75 to 86%). A
      preoperative apnea index of 32.8/hour decreased to 0.8/hour postoperatively. REM
      related falls in HbSaO2 improved remarkably. The present case suggests that
      subjects with DMD with tonsillar hypertrophy and a redundant uvula tend to
      develop noctrurnal OSA earlier than DMD cases with a normal tonsil and uvula.
      Assessment of respiratory function, particularly FEV 1.0%, is important for
      determining surgical indication of OSA in patients with DMD.

PMID- 10916379
TI  - [Successful effect of TRH-T treatment and evaluation by SPECT for an influenza
      encephalopathic patient with persistent disturbance of consciousness].

PMID- 10916380
TI  - [Revisions in the assessment of fitness for aircraft flying].
AB  - So far medical requirements for aviators have been defined by national licensing
      authorities. For a long while ophthalmological problems, insufficiencies in
      vision, refraction or color vision, have been responsible for approximately 50%
      of rejection of applicants for medical reasons. New international regulations
      proposed as well by ICAO as JAA try to lead to a new balance in these
      requirements. In general, ophthalmological requirements now allow for lower
      standards, specifically in refraction, but also in color vision. Also new
      examination methods are admitted. German and French authorities have announced
      their opposition being concerned about flight safety for the future.

PMID- 10916382
TI  - [Effect of phacoemulsification and posterior chamber lens implantation on
      intraocular pressure in patients with and without open-angle glaucoma].
AB  - BACKGROUND: Many of the previous studies which dealt with the influence of
      cataract surgery on intraocular pressure, were performed retrospectively and
      based on heterogeneous groups of patients. Therefore, the purpose of our study
      was to prospectively assess the effect of phacoemulsification and posterior
      chamber intraocular-lens (IOL)-implantation on intraocular pressure (IOP) under
      standardized conditions in patients with and without open-angle-glaucoma.
      PATIENTS AND METHODS: Overall 52 patients were recruited for the study. 34 eyes
      with normal IOP and 16 eyes with open-angle-glaucoma were operated with the same
      technique. RESULTS: Mean IOP in patients with cataract and without glaucoma was
      preoperatively 15.1 mmHg. 6 months postoperatively these patients showed a mean
      decrease of IOP of 11.9% (1.8 mmHg +/- 3.8; p = 0.027); after 12 months IOP
      showed a decrease of 18.5% (2.8 mmHg +/- 3.5; p = 0.0001). In patients with
      glaucoma mean IOP was preoperatively 17.3 mmHg. IOP was reduced by 23.7% (4.1
      mmHg +/- 6.0; p = 0.017) 6 months after cataract surgery and 22.6% (3.9 mmHg +/-
      4.5; p = 0.005) 12 months after the operation. In 6 of 16 eyes the antiglaucoma
      medication could be suspended. CONCLUSION: Reduction of IOP is a positive side
      effect of phacoemulsification and posterior chamber IOL implantation and should
      be considered when indicating cataract surgery in patients with glaucoma and only
      slight elevation of IOP.

PMID- 10916383
TI  - [Prognosis of conjunctivo-dacryocystorhinostomy. Modification with different
      implant materials].
AB  - BACKGROUND: In cases of total canalicular occlusion or the total absence of the
      lacrimal apparatus the functional restoration requires the repair of a newly
      created lacrimal system. The intraoperatively reestablisted lacrimal drainage
      from the conjunctival sac will be maintained by a plastic tube. Beside other
      criteria the influence of the used inserted materials polyethylene or silicone
      should be evaluated. PATIENTS AND METHODS: From 9/1978 to 2/1999 we have been
      treated and consecutive documented 37 cases of conjunctivodacryocystorhinostomy
      and its modifications in 36 patients (1mal both eyes). The patients (22 men, 14
      women) ranged in age from 9-76 years (mean age of 35.2 years). In a retrospective
      review results were compared for the following two groups based on the type of
      used plastic tube: group I: (n = 23); insertion of a polyethylene tube (from 1976
      1990); group II: (n = 14) insertion of a silicone tube (from 1991-1998). RESULTS:
      Causes of lacrimal drainage system obstruction were trauma (n = 21), malformation
      (n = 8), chronic inflammation (n = 5) and tumor (n = 2). The following different
      surgical techniques were performed: conjunctivodacryocystorhinostomy (cdr, n =
      23), conjunctivodacryocystostomy (cd, n = 10) and conjunctivorhinostomy (cr, n =
      4), (right eye: n = 21, left eye: n = 16). In group I 14 of 23 operations (61%)
      had successful functional results, in group II 10 of 14 operations (72%),
      respectively. The polyethylene tubes on the average were maintained for 15 months
      after surgery (4mal spontaneous removal) and the silicone tubes for 12 months,
      respectively (4mal spontaneous removal). CONCLUSION: Traumatic disturbance and
      congenital defects of canaliculi and surrounding tissue require in the case of
      any symptoms the surgical reconstruction of the lacrimal pathway. With the
      introduction of the silicone tube the success rate could be further advanced.

PMID- 10916381
TI  - [The effect of latanoprost 0.005% on pupillary reaction of the human eye].
AB  - PURPOSE: Infrared pupillography was performed to investigate the effect of one
      week topical treatment with the prostaglandin analogue Latanoprost 0.005% on
      pupillary reflex to light stimuli in glaucomatous human eyes. METHODS: Infrared
      pupillography using the compact integrated pupillograph was performed in 20
      glaucomatous eyes of 11 patients. After 10 minutes dark adaptation one pupil was
      stimulated with a blue, yellow and white diode light of 100 ms duration.
      Measurements of pupil diameter, constriction latency, constriction amplitude and
      relative constriction amplitude were taken twice for each light source in a time
      interval of 15 seconds. After a 2 week wash-out period the measurements were
      performed from 8:00 to 10:00 a.m. before and one week after topical treatment
      with Latanoprost 0.005% applied as single dose once in the evening. RESULTS: The
      measurements after 1 week treatment with Latanoprost showed a significantly
      smaller pupil diameter for blue (p = 0.044) and white stimulus (p = 0.039) and
      the latency was significantly reduced (p = 0.029) as well. CONCLUSIONS: Although
      the statistical analysis shows some small significant differences in pupil
      diameter and constriction latency there were no clinical signs of changes in
      pupillary response due to Latanoprost. The system turned out as easy to use and
      showed reliable measurements during the study. How far latanoprost may lead to
      miosis and a decrease of constriction latency has to be investigated in further
      studies with larger study populations. Other topics concerning drug influence,
      diurnal rhythm and glaucomatous damage in pupillary light reaction will be
      investigated in the near future.

PMID- 10916384
TI  - [Classical brain stem syndrome. Definitions and history].
AB  - BACKGROUND: Inaccurate definitions of brain stem syndromes in the literature.
      METHOD: The original publications of the authors during the last century and the
      early years of this one were studied in relation to the neuro-ophthalmological
      diagnosis and neuroanatomy. It is the goal of this medico-historical
      investigation to compare the knowledge available at this time when the first
      descriptions were made with the clinical experience and understanding of today.
      RESULTS: The following classical brain stem syndromes are important for an
      ophthalmologist: diseases with III-paresis: Weber's syndrome (1863, ipsilateral
      oculomotor paralysis with alternating hemiplegia), Benedikt's syndrome (1889,
      oculomotor paralysis and crossed hemiparesis with tremor), Nothnagel Claude's
      syndrome (III-Paresis with alternating ataxia); diseases with VII-paresis:
      Millard Gubler's syndrome (1856, nuclear 7th nerve palsy with crossed
      hemiparesis), Foville's syndrome (1858, conjugate lateral gaze paralysis,
      ipsilateral nuclear palsy of the 7th nerve, crossed hemiparesis); diseases with
      VI-paresis: Raymond Cestan's syndrome (1895, abducent nerve paralysis with
      contralateral hemiparesis). Brain stem lesions are also found in Wallenberg's
      syndrome (1895, Horner's syndrome, absent corneal reflex, lateropulsion of
      saccadic eye movements, nystagmus, ataxia, dysphagia, hoarseness, sensory loss
      over the facial region, contralateral dissociated diminished sensibility
      (hemiparesis), etc.). The following two syndromes do not belong to the above
      mentioned classical examples, because lesions of the long tracts of the brain
      stem are absent. However, since these two syndromes are accompanied by both
      ocular and neurological signs which indicate typical lesions of the brain stem,
      they are also mentioned here: Parinaud's syndrome (1883, paralysis of conjugate
      vertical gaze and paresis of convergence together with additional neuro
      ophthalmological signs) and the Koerber Salus Elschnig's syndrome (1903, 1910,
      1913, nystagmus retractorius, vertical gaze palsy, pupillary disturbances, and
      signs of midbrain disease). CONCLUSIONS: The first descriptions of these
      syndromes, together with the figures illustrating the neuroanatomical findings in
      these lesions, are helpful for assessing the clinical picture. Some named
      syndromes which are used today in clinical diagnosis (e.g. Parinaud's syndrome)
      do not exactly correspond to the first descriptions in the last century.

PMID- 10916385
TI  - [Lacrimal duct endoscopy with the rigid GRIN endoscopy].
AB  - BACKGROUND: Endoscopes play a more and more important role in visualizing and
      treating pathologies of the lacrimal drainage system. The present study analyzes
      the results obtained during endoscopy of the lacrimal ducts using a gradient
      index (GRIN-) endoscope. PATIENTS AND METHODS: 44 patients, 18 to 87 years old
      (mean 59 years +/- 18.9), with chronic epiphora or symptoms of affection within
      the lacrimal ducts were examined using a rigid gradient-index (GRIN-) endoscope.
      Examination was performed ambulatory using drops for local anesthesia. RESULTS:
      All 44 patients showed pathologic conditions in the lacrimal drainage system. 2
      patients had chronic changes. 25 patients had a relative stenosis (16 presaccal,
      9 postcanalicular ones). 17 patients had a total stenosis (12 presaccal, 5
      postcanalicular ones). 33 patients showed a single-sided pathology while 11
      patients showed a bilateral one. The GRIN-endoscope could be used in all patients
      and gave excellent image quality of the pathologies. CONCLUSIONS: Endoscopy with
      a GRIN-endoscope can complement the ambulatory diagnostics and therapy of the
      lacrimal drainage system. In the patient group studied (n = 44), presaccal
      pathologies (n = 28) were twice more frequent than postcanalicular ones (n = 14).
      Further developments could enlarge the indications of the GRIN-endoscope.

PMID- 10916386
TI  - [Development of neovascularization of the optic papilla, retina and iris.
      Dependence on site and extent of retinal ischemia].
AB  - BACKGROUND: Is it possible to find a correlation between the localisation of
      neovascularisations and the localisation and extension of the retinal ischemia?
      Ischemia was recognized not as capillary non-perfusion but as impaired retinal
      perfusion. MATERIALS AND METHODS: Patients with retinal ischemia like in diabetic
      retinopathy (n = 95), central retinal vein occlusion (n = 9), ischemic
      ophthalmopathia (n = 8) and branch vein occlusion (n = 5) who had
      neovascularisations were examined. The localisation of retinal ischemia and the
      localisation of neovascularisations were diagnosed by fluorescein angiography and
      biomicroscopy. RESULTS: Neovascularisations at the different places were observed
      with different frequencies depending on localisation and extension of retinal
      ischemia. Panretinal ischemia caused by diabetic retinopathy type B was followed
      by neovascularisations at iris in 69.2% with participation of the anterior
      chamber angle in 61.1%. In diabetic retinopathy type A with limited retinal
      ischemia neovascularisations of iris and chamber angle were significantly less
      frequent (31.7%/25%). On the contrary panretinal ischemia caused by central
      retinal vein occlusion was followed by neovascularisations elsewhere in 11.1%; in
      diabetic retinopathy type C with limited retinal ischemia neovascularisations
      elsewhere were observed only in 66.7%. CONCLUSIONS: There is a relationship
      between the localisation of the neovascularisations and the localisation and the
      extension of the retinal ischemia. The differentiation of PDR in different
      ischemic types is confirmed by different frequencies of the neovascularisation
      sites depending on the ischemic type. The explanation for the frequent finding of
      neovascularisations at the disk caused by the peripheral type of diabetic
      retinopathy is a communication via Cloquet's canal between periperal retina and
      papilla.

PMID- 10916387
TI  - [Melanoma inhibitory activity (MIA). Evaluation of a new tumor-associated antigen
      as a serum marker for uveal melanomas].
AB  - BACKGROUND: Currently no serological marker for the monitoring of uveal melanoma
      and its metastases is available. The novel tumor associated antigen Melanoma
      inhibitory activity (MIA) is expressed in the uveal melanoma and it's metastatic
      lesions. METHOD: We report about the serum samples of 38 patients with uveal
      melanomas. 4 of these patients had overt metastatic disease. A nonradioactive one
      step ELISA was used to quantify the MIA serum levels. RESULTS: In the 34 patients
      without overt metastatic disease the serum concentration of MIA was mean (+/- 1
      SD) 3.6 +/- 1.0 ng/ml. In the 4 patients with overt metastatic disease the serum
      concentration of MIA was mean (+/- 1 SD) 27.7 +/- 3.0 ng/ml. The difference was
      statistically highly significant (student t test: p = 0.0001). CONCLUSION: MIA is
      expressed in primary and metastatic lesions of uveal melanomas. The elevation of
      MIA serum levels in patients with metastatic disease from melanomas suggests a
      promising role as a serum marker for monitoring patients with uveal melanoma.

PMID- 10916388
TI  - [Ocular manifestation in dengue fever].
AB  - Dengue-Fever is a mosquito transmitted viral disease. It is endemic mainly in
      South-East Asia and Africa. The clinical manifestation is divided into different
      stages. Ocular manifestations in travellers have been rarely reported. PATIENTS:
      We present the cases of two patients, having just returned from a trip to
      Thailand. During their trip they had fallen ill with symptoms of classic dengue
      fever. FINDINGS: On examination visual acuity had decreased in both patients. In
      one patient we detected a relative central scotoma in perimetry and reduced
      amplitudes in VEP. In indirect ophthalmoscopy we found intraretinal haemorrhages,
      foveal lesions in the pigment epithelium, cotton-wool spots and a maculopathy.
      The fluorescein angiographic findings included extravasation in the macular
      region and block fluorescence. The diagnosis was confirmed by a rise in Dengue
      fever antibody titre and the detection of flavivirus IgM antibodies. CONCLUSION:
      Dengue-fever and its ocular manifestation in Europeans is a rare condition.
      Expanding tourism to tropical countries may lead to an increasing number of
      cases.

PMID- 10916389
TI  - [Prolonged wound healing after perforating keratoplasty. CPAP hyperbaric
      ventilators for sleep apnea as a risk factor].
AB  - Nasal hyperbaric respiration devices used at night to counteract sleep apnea may
      represent a concealed cause of delayed superficial wound healing following
      perforating keratoplasty. We report the cases of two patients whose respirators
      produced a continuous flow of pressurized air (nCPAP) onto the operated eyes,
      leading to conjunctival hyperemia, recurrent corneal erosion, infiltration of the
      puncture track and the cornea, and superficial punctate keratopathy.
      Microbiological investigation revealed no clearly identifiable pathogens. Healing
      improved consistently only after the pressurized air system had been modified so
      that no air escaped from the nostrils and the patients had been instructed in
      disinfection of the moisturizing system.

PMID- 10916390
TI  - [Sectorial corneal degeneration after glass splinter injury].

PMID- 10916391
TI  - [Bulbar protrusion, retrobulbar anterior ophthalmic vein vascular process].

PMID- 10916392
TI  - [Clinical aspects and therapy of acanthamoeba keratitis].

PMID- 10916393
TI  - Covered services for routine exam are clarified.

PMID- 10916394
TI  - The power of words: encourage bone marrow donations.

PMID- 10916395
TI  - Remembering needless workplace risk.

PMID- 10916396
TI  - West Nile virus: a new threat in Pennsylvania.

PMID- 10916397
TI  - West Nile virus questions and answers.

PMID- 10916398
TI  - Waiting room tips. What patients appreciate ... and don't.

PMID- 10916399
TI  - Alternative therapies ... getting "a second opinion".

PMID- 10916400
TI  - Tick, tick, ticking away....

PMID- 10916401
TI  - Kids & allergies don't mix.

PMID- 10916402
TI  - The Starbright program showing kids a heavenly good time.

PMID- 10916403
TI  - Making the most of your doctor visits.

PMID- 10916405
TI  - Amish country doctor.

PMID- 10916404
TI  - Antibiotics: helping or hurting you?

PMID- 10916406
TI  - "The best gift". Avoiding burnout.

PMID- 10916408
TI  - Online pharmacies.

PMID- 10916407
TI  - Latex allergy a growing problem.

PMID- 10916409
TI  - "Teaching physiology: filling a bucket or lighting a fire?".

PMID- 10916410
TI  - [Tuberculosis in Romania in 1999].

PMID- 10916411
TI  - [The clinico-epidemiological aspects of the tuberculosis incidence in the Gypsy
      population in the 4th and 5th districts of the city of Bucharest].
AB  - The study analyzes 126 gypsy patients, aged over 15, registered with tuberculosis
      over 2 years (1996-1997) in two districts of Bucharest (IV and V). The risk of
      the disease was twice larger in men than women, the age group most affected was
      30-49. For lung tuberculosis, bacteriological confirmation was 85%. 83% of
      bacteriological confirmed cases were smear positive, suggesting the high
      contagious risk at the time of the discovery. Only 48% favorable results after
      chemotherapy are partially explained by the low level of education for health in
      this population, high rate of associated diseases (66.7%) etc. Being a group with
      high risk for tuberculosis, the gypsy population needs targeted measures for
      discovering the disease and prophylaxis.

PMID- 10916412
TI  - [Nutrition and COPD].

PMID- 10916413
TI  - [The outlook in the treatment of community-acquired and nosocomial pneumonias].

PMID- 10916414
TI  - [Primary pulmonary arterial hypertension].

PMID- 10916416
TI  - [The diagnostic value of invasive methods for exploring the mediastinum].

PMID- 10916415
TI  - [Thyroid tuberculosis--a clinical case].
AB  - We present the case of a 38-year-old male patient with tuberculosis of the
      thyroid; the diagnosis was established on histological examination after surgery.

PMID- 10916417
TI  - [General considerations on pleural drainage].

PMID- 10916418
TI  - [The tuberculous patient: the subject of law].

PMID- 10916420
TI  - [Progress in smoking cessation in the countries of central and Eastern Europe-
      the first step towards bringing antismoking forces together].

PMID- 10916419
TI  - [Sarcoidosis].

PMID- 10916421
TI  - [Prof. Cornel Carpinisan (1904-1970)].

PMID- 10916422
TI  - Molecular biology of aquaporins.

PMID- 10916423
TI  - The mechanisms of aquaporin control in the renal collecting duct.
AB  - The antidiuretic hormone arginine-vasopressin (AVP) regulates water reabsorption
      in renal collecting duct principal cells. Central to its antidiuretic action in
      mammals is the exocytotic insertion of the water channel aquaporin-2 (AQP2) from
      intracellular vesicles into the apical membrane of principal cells, an event
      initiated by an increase in cAMP and activation of protein kinase A. Water is
      then reabsorbed from the hypotonic urine of the collecting duct. The water
      channels aquaporin-3 (AQP3) and aquaporin-4 (AQP4), which are constitutively
      present in the basolateral membrane, allow the exit of water from the cell into
      the hypertonic interstitium. Withdrawal of the hormone leads to endocytotic
      retrieval of AQP2 from the cell membrane. The hormone-induced rapid
      redistribution between the interior of the cell and the cell membrane establishes
      the basis for the short term regulation of water permeability. In addition water
      channels (AQP2 and 3) of principal cells are regulated at the level of expression
      (long term regulation). This review summarizes the current knowledge on the
      molecular mechanisms underlying the short and long term regulation of water
      channels in principal cells. In the first part special emphasis is placed on the
      proteins involved in short term regulation of AQP2 (SNARE proteins, Rab proteins,
      cytoskeletal proteins, G proteins, protein kinase A anchoring proteins and
      endocytotic proteins). In the second part, physiological and pathophysiological
      stimuli determining the long term regulation are discussed.

PMID- 10916424
TI  - Molecular water pumps.
AB  - There is good evidence that cotransporters of the symport type behave as
      molecular water pumps, in which a water flux is coupled to the substrate fluxes.
      The free energy stored in the substrate gradients is utilized, by a mechanism
      within the protein, for the transport of water. Accordingly, the water flux is
      secondary active and can proceed uphill against the water chemical potential
      difference. The effect has been recognized in all symports studied so far (Table
      1). It has been studied in details for the K+/Cl- cotransporter in the choroid
      plexus epithelium, the H+/lactate cotransporter in the retinal pigment
      epithelium, the intestinal Na+/glucose cotransporter (SGLT1) and the renal
      Na+/dicarboxylate cotransporter both expressed in Xenopus oocytes. The generality
      of the phenomenon among symports with widely different primary structures
      suggests that the property of molecular water pumps derives from a pattern of
      conformational changes common for this type of membrane proteins. Most of the
      data on molecular water pumps are derived from fluxes initiated by rapid changes
      in the composition of the external solution. There was no experimental evidence
      for unstirred layers in such experiments, in accordance with theoretical
      evaluations. Even the experimental introduction of unstirred layers did not lead
      to any measurable water fluxes. The majority of the experimental data supports a
      molecular model where water is cotransported: A well defined number of water
      molecules act as a substrate on equal footing with the non-aqueous substrates.
      The ratio of any two of the fluxes is constant, given by the properties of the
      protein, and is independent of the driving forces or other external parameters.
      The detailed mechanism behind the molecular water pumps is as yet unknown. It is,
      however, possible to combine well established phenomena for enzymes into a
      working model. For example, uptake and release of water is associated with
      conformational changes during enzymatic action; a specific sequence of allosteric
      conformations in a membrane bound enzyme would give rise to vectorial transport
      of water across the membrane. In addition to their recognized functions,
      cotransporters have the additional property of water channels. Compared to
      aquaporins, the unitary water permeability is about two orders of magnitude
      lower. It is suggested that the water permeability is determined from chemical
      associations between the water molecule and sites within the pore, probably in
      the form of hydrogen-bonds. The existence of a passive water permeability
      suggests an alternative model for the molecular water pump: The water flux
      couples to the flux of non-aqueous substrates in a hyperosmolar compartment
      within the protein. Molecular water pumps allow cellular water homeostasis to be
      viewed as a balance between pumps and leaks. This enables cells to maintain their
      intracellular osmolarity despite external variations. Molecular water pumps could
      be relevant for a wide range of physiological functions, from volume regulation
      in contractile vacuoles in amoeba to phloem transport in plants (Zeuthen 1992,
      1996). They could be important building blocks in a general model for vectorial
      water transport across epithelia. A simplified model of a leaky epithelium
      incorporating K+/Cl-/H2O and Na+/glucose/H2O cotransport in combination with
      channels and primary active transport gives good quantitative predictions of
      several properties. In particular of how epithelial cell layers can transport
      water uphill.

PMID- 10916425
TI  - Role of lateral intercellular space and sodium recirculation for isotonic
      transport in leaky epithelia.

PMID- 10916426
TI  - Pathogenesis of heart failure--2000.

PMID- 10916427
TI  - Nonpharmacological treatment of atrial tachycardia.
AB  - The authors analyse the efficacy and safety of catheter ablation and atrial
      pacing for the treatment of atrial tachycardia. Radiofrequency catheter ablation
      was selected whenever the arrhythmogenic focus was located on the free-wall or in
      the meso-septal area of the right atrium. In opposition, overdrive atrial pacing
      was chosen for tachycardias originating near the sinus complex or in the left
      atrium. Both therapies were safe, but had a low efficacy in converting the
      tachycardia into sinus rhythm. However, catheter ablation allows an irreversible
      destruction of small septally located foci. Thus, both the anatomical and the
      electrophysiological characteristics of the foci can be important factors in the
      selection of the most appropriate nonpharmacologic therapy.

PMID- 10916428
TI  - Atrial tachycardias.

PMID- 10916429
TI  - Repolarization abnormalities after catheter ablation of differently located overt
      accessory pathways.
AB  - PURPOSE: Electrical repolarization abnormalities are usually seen after
      radiofrequency catheter ablation in overt accessory atrio-ventricular pathways.
      These abnormalities have been recognised as "cardiac memory". The aim of this
      study was to assess the relationships between electrical repolarization
      abnormalities and the location of the accessory atrioventricular pathway in the
      atrio-ventricular junction. We also assessed the relationship between electrical
      repolarization abnormalities and the degree of ventricular preexcitation.
      MATERIAL AND METHODS: Our group consisted of 45 patients with overt and
      persistent preexcitation who were successfully submitted to radiofrequency
      catheter ablation. Mean age was 38.9 +/- 14.9 years (14 to 64), 28 of whom
      (62.2%) were male and 17 (37.8%) female. The location of accessory pathways the
      was left lateral in 14 patients, right posteroseptal in 14 patients, right
      mesoseptal in eight patients, right anteroseptal in four patients and other
      locations in the remaining four. Surface electrocardiograms were performed
      immediately following ablation, 24 hours later and three or more months after the
      procedure. RESULTS: T wave abnormalities (flattened, inverted or peaked) were
      detected on the first day in 51% of patients, being more frequent after right
      accessory pathway ablation (86.9% versus 13.1% in left accessory pathways). These
      electrocardiographic changes were particularly frequent in patients with right
      mesoseptal (5/8, 62.5%) and posteroseptal (13/14, 93.3%) pathways, of which 62.5%
      and 71.5%, respectively, showed marked preexcitation before ablation. These
      findings were significantly different from those observed in patients with left
      lateral pathways--only 35.7% showed marked preexcitation and only two of fourteen
      patients (14.3%) presented T wave abnormalities after ablation. After the third
      month, most of the patients that had undergone successful ablation presented
      completed electrocardiographic normalization. CONCLUSIONS: Patients undergoing
      radiofrequency catheter ablation for right accessory pathways show more
      frequently repolarization abnormalities than those submitted to ablation of the
      left lateral accessory pathways. The occurrence of these changes after
      preexcitation resolution may depend on the degree of previous preexcitation.

PMID- 10916430
TI  - Unstable angina: individualized stratification and prognosis.
AB  - OBJECTIVE: To analyse the methodology of risk stratification and the prognosis of
      patients admitted with unstable angina. POPULATION AND METHODS: This
      retrospective study involved a population of 68 patients (43 males and 25 females
      with a mean age of 65.8 +/- 9.8 years) consecutively admitted for suspected
      unstable angina during the year of 1996. Thirty six patients (52.9%) had angina
      at rest, 13 patients (19.1%) had both exertional and rest angina, 9 patients
      (13.2%) crescendo angina, 6 patients (8.8%) new onset exertional angina (less
      than 1 month), and 4 patients (5.8%) post-infarction angina (less than 2 weeks).
      The risk stratification was individualized. The coronary angiography (35
      patients) was only performed when the medical therapy failed in patients with
      recurrent angina, or with proved ischemia after an exercise test and/or thallium
      201 stress scintigraphy. Thirteen patients (19.1%) did not undergo these tests
      (advanced age and or bad general condition, or refusal). The follow-up of
      patients with and without ST-T changes was compared, as well as those
      revascularized versus non-revascularized. It was possible to achieve a mean
      follow-up of 13.7 +/- 6.2 months (3 to 25 months). RESULTS: The exercise test
      and/or thallium-201 stress scintigraphy were positive for myocardial ischemia in
      28 pts (41.1%) and negative in 7 patients (10.2%). The coronary angiography
      revealed three-vessel coronary artery disease in 18 patients (26.4%), one vessel
      disease in 11 patients (16.1%) and two-vessel disease in 5 patients (7.3%). One
      patient had normal coronary arteries. Medical therapy was the initial approach.
      Coronary surgery was urgently performed in 3 patients and coronary angioplasty in
      5 patients for refractory unstable angina. In the whole group coronary artery
      surgery was undertaken in 14 patients (20.5%) and coronary angioplasty in 12
      patients (17.6%). A mean follow-up of 13.7 +/- 6.2 months was obtained in the 68
      patients. During this period 6 patients (8.8%) died due to cardiac causes and 16
      patients (23.5%) were readmitted: 8 patients (11.7%) for unstable angina, 5
      patients (7.3%) for congestive heart failure and 3 patients (4.4%) for myocardial
      infarction. Fifty two patients (76.4%) remained free of cardiac events. The
      patients with transitory ST-T changes had more cardiac events (unstable angina,
      myocardial infarction, mortality) than the patients without ECG changes (13/30 vs
      2/30, p = 0.003). When the revascularized patients were compared to the non
      revascularized no significant differences were observed regarding myocardial
      infarction and mortality, however revascularized pts had a less significant
      incidence of rehospitalization for unstable angina (0/26 vs 8/42 p = 0.02).
      CONCLUSIONS: An individualized strategy can be effective in pts with unstable
      angina. In this study 76.4% of patients remained free of cardiac events during
      the follow-up, 23.6% had severe cardiac events and the cardiac mortality was
      8.8%. The patients with transitory ST-T changes had more cardiac events and worse
      prognosis. No patients significant difference was observed in the revascularized
      versus non revascularized patients for myocardial infarction and mortality;
      however, the revascularized patients had less significant incidence of
      rehospitalization for unstable angina.

PMID- 10916432
TI  - [Recommendations for the diagnosis and treatment of unstable angina and non-Q
      wave myocardial infarction (proposed revision)].
AB  - The optimal diagnostic and treatment strategies for unstable angina/non-Q-wave
      myocardial infarction patients will continue to be redefined as rapid progress is
      made in the understanding, and treatment of this syndrome. The recommendations
      presented here reflect, in part, discussions at the International Cardiology
      Forum in September 1998. Although areas of controversy remain, we have summarized
      major points on which a consensus could be reached and for which the weight of
      the clinical evidence supports a change in practice.

PMID- 10916431
TI  - [Prognosis significance of blood homocysteine after myocardial infarction].
AB  - INTRODUCTION AND AIMS: Homocysteinemia is an independent risk factor of coronary
      artery disease and of myocardial infarction. In the present study we intend to
      relate fasting homocystein levels to prognosis after a myocardial infarction.
      METHODS: From 1990 to 1992, we studied fasting homocysteinemia levels on a group
      of 112 patients aged under 56 years that had suffered a myocardial infarction
      between 3 and 12 months before. We obtained, the patients names, addresses, phone
      numbers and physicians' name. Seven years later (on average) we collected data
      regarding the patients evolution, consulting medical records, their physicians or
      by personal contact. We evaluated complications, namely mortality, vascular
      morbidity, such as unstable angina, re-infarction, stroke, and the need for
      invasive procedures (catheterism, PTCA, CABG). According to previous studies of
      the group, we used a cut-point of 10.10 mumol/L to define patients with normal or
      pathological levels of homocysteinemia. We excluded all patients that took
      vitamin B supplements, co-factors of HC metabolism, during this follow-up.
      RESULTS: We were able to obtain data on 110 patients. Patients with normal HC
      levels (n = 62) presented less global complications (26 versus 72%, p < 0.0001),
      non significant tendency to have lower mortality (1.6 versus 6%), had lower
      morbidity (14 versus 36%, p < 0.01) and lower invasive procedure need (18 versus
      48%, p < 0.001). In the group with pathological homocystein levels (n = 48),
      those with higher homocystein levels presented a higher degree of complications.
      CONCLUSIONS: In this population with myocardial infarction under 56 years of age,
      a high homocysteinemia level is an important prognostic factor. This study
      suggests that we can improve the prognosis and decrease the complications after
      myocardial infarction by lowering elevated homocystein levels.

PMID- 10916433
TI  - [Indexes for the evaluation of scientific publications: what they are and what
      they are used for].
AB  - Today, medicine lives the paradigm of Evidence-Based Medicine, which integrates
      the most recent discoveries of Research in day-to-day Clinical Practice.
      Simultaneously, there is an exponential growth in biomedical scientific
      knowledge, and, with it, of the number of scientific papers and biomedical
      journals. Currently, the assessment of the quality of biomedical scientific
      information is based on the peer review method, which also has different types of
      bias. In this setting, quantitative indexes are increasingly being used to assess
      it. Three of these indexes are the quotation rate, the impact factor and the
      Immediacy Index that, despite their objectivity, have several limitations. The
      impact factor, which is a valid tool to estimate the quality of a scientific
      journal, is not suited to evaluate single articles, scientists or research
      groups. In these cases, the best methodology is quotation analysis. No method,
      however, can replace the individual reading and study of the contents of the
      scientific work. Of the new potentialities of biomedical information, the
      possibility of discussing scientific articles before their publication is
      particularly promising. With this purpose, the netprints servers, which are new
      sites on the Internet, were created. Other sites where we can have access to
      databases with summaries of guidelines have also been created in an attempt to
      reduce the gap between research and clinical practice.

PMID- 10916434
TI  - [Isolated infective endocarditis of pulmonary valve in patient with
      interventricular septal defect].
AB  - A case of isolated infective endocarditis of the pulmonary valve in a patient
      with known subpulmonary interventricular septal defect that had, as major
      complication pulmonary septic embolization, was reported by the authors. The
      disease followed an insidious course, diagnosed by the presence of vegetations in
      the echocardiogram, some of them larger than 1 cm. They were found in the right
      ventricular infundibulum and in the pulmonary valve leaflets. The isolation of
      Estreptococcus viridans in blood cultures has confirmed the diagnosis. In spite
      of appropriate antimicrobial therapy, according to the antibiogram data (with
      Ampicillin and Gentamicin), fever lasted for more than three weeks. This event
      suggested medical treatment failure and the possibility of surgery was
      considered. However, the endocarditis eventually healed with medical therapy
      alone, and this unusual course with prolonged fever was presumed to be caused by
      lung metastatic infection secondary to septic embolization. This complication is
      relatively common, but lung involvement is usually a subclinical event, not
      responsible for such persistent fever, as happened in the case now reported. We
      emphasize the rarity of this case, the unusual clinical course and the discussion
      concerning the therapeutic options.

PMID- 10916435
TI  - [Giant aneurysm of the left ventricle].

PMID- 10916436
TI  - [Ascending aorta dissection as a cause of myocardial infarction].

PMID- 10916437
TI  - Public reporting of surgical mortality: a survey of New York State cardiothoracic
      surgeons.

PMID- 10916438
TI  - [Results of conservative therapy in early breast carcinoma].
AB  - The authors present a review on the development of views on breast cancer from
      the beginning of the century and contemporary views on the problem, its solution
      world-wide and in the Czech Republic. They base on their own group of 475
      patients of 1991-1998, they analyze the development of possible solutions of
      early breast cancer and their view on the discussed problem. With regard to
      favourable results they advocate progressive breast preserving operations
      associated with postoperative radiotherapy and the use of the method of sentinel
      nodes.

PMID- 10916439
TI  - [Blunt tracheobronchial injuries in children].
AB  - Blunt tracheobronchial injuries in children are rare and are associated with many
      diagnostic problems. Based on the successful outcome in a seven- and a twelve
      year-old patient operated within 12 hours after the accident the authors discuss
      the development of the symptomatology and early clinical, X-ray, bronchoscopic
      and CT diagnosis of rupture which are, if intensive care and early treatment of
      the injury are ensured, the basis for preserving normal pulmonary function and
      ensure prevention of sequelae due to obstruction and infection. The children were
      admitted to hospital for 22 and 14 days resp. and discharged in a good condition.
      The check-up examinations of both patients are within the normal range and there
      are no limitations as compared with healthy children of the same age.

PMID- 10916440
TI  - [Clinical and histopathologic picture of acute appendicitis in children].
AB  - A retrospective study of the clinical and histopathological picture of acute
      appendicitis in children confirms agreement of the evaluation of the finding on
      the appendix made by the surgeon and pathologist in 72.2% and disagreement in
      27.8%. The finding is overrated in 11.3% and underrated in 16.5%. Agreement is
      closest in phlegmonous appendicitis (88.1%) and lowest in gangrenous appendicitis
      (54.9%). The most frequently overrated finding is in catarrhal appendicitis
      (20.7%). The number of missed appendectomies is from the pathologist's point of
      view significantly lower (21.8%) than from the surgeon's point of view (34.7%).
      This indicates obviously that it is not possible to make an accurate macroscopic
      assessment of the progress of appendiceal inflammation. The number of "negative"
      appendectomies is according to the surgeon 15.8% and according to the pathologist
      16.8%, i.e. almost equal.

PMID- 10916441
TI  - [Detection of acute appendicitis using ultrasonography].
AB  - 1318 patients with a clinically equivocal diagnosis of appendicitis were
      evaluated using graded compression sonography. Sonographic (US) examination could
      able be performed in 1199 patients. Appendicitis was diagnosed if the appendiceal
      maximal mural thickness was 3 mm or more, or the appendices presented with
      luminal dilatation due to a large appendicolith or non-expressible fluid. In
      patients with verified appendicitis (n = 176) sonographic findings on a
      visualized appendix were correlated with surgical and histopathological findings.
      In patients who did not have surgery the reference standard was the clinical
      consensus based follow-up. A pathological appendix was detected in 165 cases of
      176 surgically verified ones. The sensitivity of US in detecting appendicitis was
      93.7%, the specificity 95.5% and the accuracy 95.2%.

PMID- 10916442
TI  - [Diverticulosis of the small intestine--case report].
AB  - The authors describe the case of a 86-year-old female patient admitted to
      hospital with acute abdomen of the inflammatory type. The condition developed in
      the course of cca three days with sudden deterioration on the day of admission to
      hospital. Contrast X-ray examination revealed perforation of the distended
      jejunum and surgery revealed diffuse peritonitis the source of which was the
      mentioned perforation associated with mechanical ileus caused by malrotation and
      adhesions of the small intestine. An additional finding which, however, dominated
      on X-ray examination of the gastrointestinal tract when using contrast material
      and on revision of the peritoneal cavity was multiple diverticulosis of the small
      intestine. The uncommon finding on the small intestine and the relatively sparse
      data in the literature on diverticulosis of the jejunum and ileum made us submit
      the case-history for publication.

PMID- 10916443
TI  - [Classic carcinoids of the appendix].
AB  - Nine classic carcinoids smaller than 2 cm, situated elsewhere than at the base of
      the appendix have been diagnosed in the Department of Pathology of the University
      Hospital in Olomouc during the period from 1994 to 1999. Appendectomy including
      removal of the mesenteriolum was performed in all cases. The literature mentions
      favourable prognosis of patients with small appendiceal carcinoids--100 per cent
      5-year survival rate. Tumours greater than 2 cm recur and metastasise. These
      tumours require oncological therapy in cases with unresectable metastases. This
      worsens the 5-year survival rate to 21-42%.

PMID- 10916444
TI  - [Fixation of a non-adjustable gastric band using an anterior gastric wall cuff
      (randomized study)].
AB  - We have been concerned with bariatric surgery at the First Surgical Clinic of th
      General Faculty Hospital, First Medical Faculty, Charles University Prague since
      1983. In 1983-1986 vertical gastroplasties were made, between 1986 and 1993 non
      adjustable gastric bands were provided by the laparotomic approach. Since 1993
      when we were the first to implement a gastric band operation (GB) by the
      laparoscopic route, this method is used as the standard method. In 1993-1998 we
      made at the First Surgical Clinic 517 laparoscopic GB operation on account of
      morbid obesity in patients with a body mass index of 34-49 kg/m2. The group
      comprised 449 women and 59 men. The most frequent late complication in our group
      of morbidly obese patients who had a laparoscopically administered GB was in 5.1%
      enlargement of the proximal pouch above the GB by dilatation of its wall or
      slippage of the anterior wall proximally under the GB with a subsequent disorder
      of gastric evacuation and vomiting. We tried to reduce the incidence of this
      complication by fixing the GB by a cuff made from the anterior gastric wall. To
      test the effectiveness of the suggested fixation of the non-adjustable GB by a
      cuff we implemented in 1998-1999 a prospective randomized study in a group of 80
      morbidly obese patients divided into experimental group n1-GB + C with the cuff
      and a control group n2-GB - C without a cuff. We investigated the incidence of
      the mentioned complication and the changed volume of the pouch above the GB after
      one year. Endoscopic assessment of the size of the pouch above the GB after
      surgery and after one year revealed that in group n1-GB + C the mean increase of
      the pouch volume was 14.6 ml, i.e. 124% of the original size, while in group n2
      GB - C the mean increase of the volume was 33.6 ml, i.e. 154.1% of the original
      size (p < 0.001). Based on the assembled results and aware of the fact that small
      groups were involved, we should like to express the assumption that the suggested
      modification, i.e. fixation of a non-adjustable GB by a cuff made from the
      anterior gastric wall can reduce the incidence of the complication of slippage of
      the anterior gastric wall proximally above the bandage.

PMID- 10916445
TI  - [Biliary tract injury in laparoscopic cholecystectomy--case report].
AB  - The author presents a case of injury of the efferent biliary pathways after
      laparoscopic cholecystectomy in a 81-year-old female patient. Reconstruction of
      the injury is always an important procedure for the patient not only with regard
      to immediate postoperative complications but also for his future life. Referring
      the patient to a superior department is indicated but often impossible. The
      author summarize briefly the principles of treatment. After revision which was
      more than 5 weeks after the primary operation the patient survived the
      reconstruction and is now, after 18 months, in good health.

PMID- 10916447
TI  - [Liver resection using the harmonic scalpel].
AB  - The authors present their initial experience with the use of a harmonious scalpel
      in resections of the liver. The harmonious scalpel was used as part of the
      resection technique in 24 patients operated in 1999. Indication for surgery was
      in five patients benign liver disease (inborn cysts, nodular hyperplasia,
      haemangioma, hepatocellular adenoma) and in 19 malignant disease (hepatocellular
      carcinoma and secondaries). Anatomical resection of the liver was performed in 15
      patients and in 9 patients a wedge-shaped resection. During resection a combined
      technique with a harmonious scalpel was used (with coagulation scissors). As to
      postoperative complications two patients developed cholascos. According to the
      authors' experience introduction of a harmonious scalpel into the technique of
      liver resection is the method of choice in particular in non-anatomical
      resections because of the better control of haemorrhage and safer isolation of
      bile ducts and blood vessels.

PMID- 10916446
TI  - [Mini-invasive procedures in the treatment of complicated retroperitoneal
      hemorrhage in a patient with multiple injuries].
AB  - The authors present the case-history of a patient with multiple injuries where
      the dominating injury was haemorrhage into the retroperitoneum and subsequently
      into the abdominal cavity. The solution after CT and sonographic diagnosis was
      laparoscopy and subsequent arteriography with embolization. The authors consider
      the described procedures as the most suitable one in the given case.

PMID- 10916448
TI  - [Etiopathogenesis, diagnosis and treatment of aneurysms of the abdominal aorta in
      the year 2000].
AB  - The author presents an account of the present status in the sphere of
      epidemiology, etiopathogenesis, diagnosis and treatment of an aneurysm of the
      abdominal aorta (AAA). Based on the experience from his own department and data
      in the literature he summarizes recent findings in particular on the
      etiopathogenesis and treatment of AAA. Research on the etiopathogenesis of AAA is
      focused at present mainly on inflammatory processes in the aortal wall leading to
      subsequent destruction of the intercellular matrix. An important part is pleayed
      by inflammatory cells (macrophages, T and B lymphocytes), smooth muscle cells of
      the media and fibroblasts. Important information molecules in the inflammatory
      process are cystokines. However the causal factor or factors which start the
      process are still unknown. Hypertension and smoking are important risk factors
      for the development of AAA. The contemporary rapidly developing trend of
      treatment of AAA are endovascular operations which have however technical
      limitations and so far long-term results are not known. An obvious advantage, as
      compared with classical surgical treatment, is the sparing operation and the
      short hospitalization of the patient. A certain disadvantage is the necessity of
      permanent follow up of the patient by duplex sonography or CT and a certain
      percentage of complications associated with this technique which calls for
      subsequent endovascular or surgical operations. It is therefore difficult to
      compare the economic cost of endovascular and surgical treatment. The objective
      of research, diagnostic and therapeutic efforts in the near future should be
      reduction of the incidence of AAA ruptures (40% of all AAA is manifested first by
      rupture) and better therapeutic results (the mortality is at present 30-70%).

PMID- 10916450
TI  - [Thyroid gland carcinoma from a retrospective view].
AB  - The authors analyze a group of 32 patients with thyroid cancer. They always
      dissect the recurrent nerve and search for the parathyroid glands. They draw
      attention to the constant course of the branch of the lower thyroid artery
      beneath the ligament of Berry. In their opinion the basic operation comprises
      bilateral total lobectomy with cervicocentral lymphadenectomy. In case of
      scintigraphic, USG or CT evidence of secondaries in the other cervical triangles,
      they make after some interval a modified cervical dissection. They make a
      circular resection of the invaded cervical trachea. Peroperative histology makes
      a so-called single-stage operation possible.

PMID- 10916449
TI  - [Autogenous bilateral aortofemoral reconstruction using the popliteal and
      superficial femoral veins].
AB  - The author presents a case-history of a late infection of a bilateral
      aortofemoral bypass by a coagulase-negative staphylococcus and the definite
      solution by substitution of the contaminated vascular prosthesis by an anatomical
      autogenous bilateral bypass made from popliteal and superficial femoral veins.
      From the technical aspect the operation was very satisfactory without marked
      peroperative difficulties, the early postoperative course was also favourable,
      with readily palpable peripheral pulsations, without marked manifestations of
      venostasis on the lower extremities. From the third postoperative day onwards
      however progressive manifestations of multiorgan failure developed associated
      with septic shock and leading to a fatal outcome. Despite this the author
      considers in patients with a reasonable surgical risk this method of substitution
      of an infected vascular prosthesis in the aortofemoral region feasible with
      regard to its resistance to infection and long-term patency, though the operation
      is technically pretentious but easy to implement.

PMID- 10916451
TI  - [Modern trends in the treatment of diffuse peritonitis].
AB  - The authors describe new approaches to the treatment of diffuse peritonitis,
      using the Mannheim Peritonitis Index scoring system. Depending on the score, the
      authors determined the types of additional surgical procedures such as "sipping
      drainage", laparostomy and repeated laparotomies.

PMID- 10916452
TI  - [Treatment of blunt injuries of the spleen in children].
AB  - The authors report study of patients with blunt splenic trauma treated at
      Paediatric Surgery Department in years 1991-1999. During 9 years period 50
      patients (36 males, 14 females) with demonstrated rupture of the spleen were
      analyzed. 46 patients (92%) were treated conservatively (group A). Complications
      appeared in 7 patients (15.22%), rebleeding in two patients, arterio-venous
      fistula in early posttraumatical period in one patient and during control in one
      patient, fluidothorax in two patients and posttraumatic pseudocyst of the spleen
      in one patient. Four patients (8%) were operated (group B). Two of them submitted
      splenectomy, one patient was treated by splenorrhaphy and one patient by partial
      splenectomy. Period of the hospitalization in average lasted in group A 12,67
      days, in group B 15 days. With regard to the immunologic functions of the spleen
      especially in childhood authors prefer conservative treatment, in case that
      laparotomy is inevitable authors try to preserve the spleen.

PMID- 10916453
TI  - [Yeast infections in patients in a surgical intensive care unit].
AB  - The authors evaluate importance of candida infections in a surgical ICU. They
      present recent survey of aetiology, pathogenesis, diagnostic methods, clinical
      manifestations and therapy of invasive candida infections. The aim of this
      article is especially to summarize risk factors of the candida infection
      development.

PMID- 10916454
TI  - [Malignant lymphoma of the small intestine as an uncommon cause of obstructive
      ileus].
AB  - The authors draw attention to an uncommon cause of obstructive ileus in children,
      i.e. malignant lymphoma of the small intestine in a 10-year-old boy.

PMID- 10916455
TI  - [Intramedullary nailing using the Medin tibial nails].
AB  - In a prospectively followed up group of 163 nailed tibiae in 157 casualties after
      4-48 months, on average after 15 months following implantation 20 patients
      (12.5%) developed complications. In two instances the nail broke or was bent
      (1.25%), the remaining complications were not associated with the implant or
      instruments. Subsequent tests however did not prove defective material of the
      damaged nails. Medin nails are a reliable, readily available and cheap implant.

PMID- 10916456
TI  - [Epistola chirurgica. VIII. Hand injuries].

PMID- 10916457
TI  - [Quantitative analysis of the electroencephalogram in healthy school-age
      children].
AB  - Topography of EEG power spectra in a sample of 72 healthy children aged 7 to 15
      years, was studied. The children were volunteers, satisfying general criteria of
      normality. The EEGs were recorded at 16 scalp locations in subjects with closed
      eyes and measured in monopolar recording on a split screen of a system for video
      EEG monitoring. Each signal of EEG channels was digitized with 12-bit resolution
      and processed by a PC computer. The raw EEG was transformed by fi-time domain
      into the frequency domain using the fast Fourier transforms. In-transformed
      absolute power and relative power were used as parameters. In the present study
      it was shown that total power was mainly influenced by alpha power. Maximal delta
      activity exhibited in anterior and posterior derivations, while minimal activity
      was measured in central and mid-temporal locations. Theta power was mostly
      pronounced in posterior derivations. Beta-1 band activity was maximal in
      posterior and minimal in anterior derivations. Significant power decrease in beta
      2 power was also characteristic of posterior locations. Diagrammatic presentation
      of In-transformed absolute power over brain regions (frontal, central, midparieto
      occipital and temporal) gave a summary of distributions shown earlier. Most of
      the relative powers were found in alpha band, especially in parieto-occipital
      region.

PMID- 10916458
TI  - [Autoimmune hepatitis in children].
AB  - Autoimmune hepatitis is a rare chronic disease of unknown aetiology with female
      predominance, circulating autoantibodies, hypergammaglobulinaemia, typical major
      human leukocyte antigen types (HLA A1/B8/DR3) and a good response to
      immunosuppressive therapy. It seems that the main features in autoimmune
      hepatitis are a primary or secondary defective suppressor-T-cell function.
      Recently, we are realizing the recommendations of the International Autoimmune
      Hepatitis Study Group, using a combination of clinical, biochemical and
      serological features. METHODS: Two hundred and twenty one patients with chronic
      liver disease were studied. In this study, 221 consecutive percutaneous liver
      biopsies were performed, with a Menghini needle, during a 5-year period. All
      children were under 18 years. RESULTS: We found 17 patients with autoimmune
      hepatitis (7.7%) among children with chronic liver disease. In summary, final
      diagnosis was established in 16 patients (94%). Using minimum required (main)
      parameters final diagnosis was established in 10 patients (59%). We found no
      significant differences between histologic parameters and response to therapy.
      Our patients with autoimmune hepatitis were predominantly females (3.25:1) with
      antibodies to smooth muscle (59%). The main histologic findings were bridging
      necrosis, rosetting of the liver cells and plasma cell infiltration (83%). In two
      cases we found granulomas and in one case centrilobular necrosis. DISCUSSION AND
      CONCLUSION: Over a period of 5 years, the diagnosis of autoimmune hepatitis was
      established in 17 children. This is similar to the findings published in other
      paediatric studies [7, 8]. Patients were predominantly females as in the most
      recent studies [10, 11, 13-15]. Our results regarding the validation of the
      scoring system showed that we found no significant differences between histologic
      parameters and response to therapy [16-18]. Histologic findings were not
      pathognomonic but suggestive of autoimmune hepatitis diagnosis [1, 4, 8, 15-18].
      The remission rate induced by the initial therapy was 88%, but in 53% of cases
      the disease was reactivated [3, 4, 11, 14, 15].

PMID- 10916459
TI  - [Factors which affect long-term patency in femoro-popliteal bypass].
AB  - INTRODUCTION: The aim of this study was to investigate how "run off", diabetes,
      cigarette smoking and early reinterventions influence long-term patency of the
      "reversed" and "in situ" femoro-popliteal (F-P) bypass grafts. PATIENTS AND
      METHODS: The study included 1991 patients with "reversed" F-P and 99 patients
      with "in situ" F-P bypass grafts operated on between 1988 and 1994. There were
      153 (80.10%) male and 38 (19.90%) female patients in the group with "reversed"
      bypass and in the group with "in situ" bypass there were 78 (78.8%) male and 21
      (21.2%) female patients. The average age of all patients was 59.04 (27-80) years.
      Eighty five (44.5%) patients in the group with "reversed" F-P bypass had diabetes
      mellitus and 43 (43.4%) in the group with "in situ" bypass. One hundred and fifty
      two (79.68%) patients in the group with "reversed" bypass were cigarette smokers
      and 80 (80.8%) in the group with "in situ" bypass. In Table 1 patients according
      to Fontain's classification of occlusive arterial disease are presented. On the
      basis of angiographic examination all patients were divided into four groups
      (with patent all 3 crural arteries, with patent 2 crural arteries, with patent
      one crural artery and without patent crural arteries) (Table 2). All patients
      were controlled using physical and Doppler ultrasonographic examinations
      immediately after the operation; after 1, 3, 6 months and then every year
      postoperativelly. In cases with suspected graft occlusion or any other
      complication, control angiography has also been carried out. Statistical analysis
      of the results was performed using chi 2 and Fisher's test. RESULTS: The patients
      were followed-up from 3 to 10 years. In cases with patent all 3 crural arteries
      there was no significant difference in long-term patency between "reversed" and
      "in situ" bypasses (Fisher's test, P = 0.66; p > 0.05) (Graph 1). In cases with
      patent two crural arteries, there was no significant difference between groups
      with "reversed" and "in situ" bypasses chi 2 = 0.25, p > 0.05) (Graph 2). The
      long-term patency was significantly better in the group with "in situ" bypass if
      only one crural artery was patent (chi 2 = 4.96, p < 0.05) (Graph 3). In cases
      with occluded all three crural arteries there was no significant difference in
      long-term patency between the two examined groups (Fisher's test, P = 0.29; p >
      0.05) (Graph 4). There was no significant difference between groups with
      "reversed" and "in situ" bypasses in patients with diabetes mellitus (chi 2 =
      0.01; p > 0.05) (Graph 5). There was also no statistically significant difference
      between the two examined groups regarding the preoperative cigarette smoking (chi
      2 = 0.94; p > 0.05) (Graph 6). However, in both groups postoperative cigarette
      smoking showed a statistically significant decrease in long-term patency (chi 2 =
      66.71; p < 0.01) (Graph 7). The early REDO operations statistically significantly
      decreased long-term patency in both groups (chi 2 = 34.89; p < 0.01) (Graph 8).
      The late graft occlusions were found in 60 patients with "reversed" and 23
      patients with "in situ" F-P bypasses. Table 3 shows causes of late graft
      occlusions. CONCLUSION: In some cases with pure "run off" "in situ" bypass
      technique showed better long-term patency. We preferred this technique when "run
      off" was pure, when diameter of the saphenous vein was small, and when bypass was
      "long". Diabetes mellitus had no significant influence on long-term graft patency
      in both groups, as well as regarding preoperative cigarette smoking. However,
      postoperative cigarette smoking and early REDO operations, statistically
      significant by decreased long-term graft patency in both groups. The reason was
      that cigarette smoking was not permitted postoperatively, while in cases with
      early reinterventions physical screening and ultrasonographic examinations were
      necessary.

PMID- 10916460
TI  - [Post-traumatic systemic fat embolism syndrome. Retrospective autopsy study].
AB  - INTRODUCTION: The obstruction of blood vessels or heart chambers with fat
      globules, reached by circulation, is fat embolism [1, 2]. Clinical manifestation
      of the presence of fat emboli in vital organs is Fat Embolism Syndrome (FES).
      This syndrome is characterized by neurologic, respiratory and cutaneous signs and
      different symptoms [5-8], grouped in major and minor signs by Gurd and Wilson.
      PURPOSE: The purpose of this paper is to analyze and compare the autopsy findings
      and clinical data in cases where FES is emphasized as the single or concurrent
      cause of death after performed autopsy. MATERIAL AND METHOD: This retrospective
      study includes the autopsy material of the Institute of Forensic Medicine in
      Belgrade, over the period 1985-1998 when FES is pointed out as a cause of death.
      The severity of trauma for each case was determinated by Injury Severity Score
      (ISS). The microscopical findings, which are incorporated in autopsy reports,
      were separately analyzed. The sample was statistically prepared (chi 2 test,
      ANOVA). RESULTS: The sample included 56 patients: 43 males (average age 51.65
      years) and 13 females (average age 65.07 years). The proportion of men was more
      significant (chi 2 test = 8.98; p < 0.01) as well as the persons aged 60-80 years
      (ANOVA, p = 0.0017). In our sample there were more pedestrians (32 patients)
      (Anova, p-->0) than other injured persons. Fractures of the femur, tibia and/or
      pelvic bones were typical injuries in each examined patient. The authors combined
      the clinical and autopsy data in order to get the ISS value. The mean ISS value
      was 20.65 (SD = 7.47). The mean value of the surviving period was 5.8 days (SD =
      3.6). The sample distribution of surviving period was normal (Gauss
      distribution). The latent period from injury to the onset of the first major FES
      signs was about 24 hours (32 patients had one of the major FES signs during the
      first 24 hours after admission; 8 patients after 24-48 hours and 10 after 48
      hours after admission). Six patients who were admitted in deep coma were not
      analyzed. DISCUSSION: The most common first major FES sign refers to the sudden
      onset and rapid progressive qualitative or/and quantitative disturbance of
      conciousness (deep coma developed after a short period, without obvious causes)
      in 40 cases. In six patients ophthalmological characteristic retinal blood
      vessels changes were found: they pointed to FES. The second major FES sign was
      respiratory disturbance alone (manifested at first as chest pain and spitting of
      blood, and later as disturbances in artery blood gas analysis), or in combination
      with disturbed conciousness--in 15 cases The characteristic later developed
      cutaneous chest and axillary rush as the only specific FES sign was established
      in 11 cases (surviving period was from 5 to 12 days), but clinically only in one
      case. In addition to objective difficulties, in most cases, one of the minor FES
      signs was established: in 22 cases haematological disturbances (i. g. low value
      of haematocrit, haemoglobin, number of platelets or/and coagulation factors); in
      13 cases hyperpirexia, and other minor FES signs only occasionally. The
      postmortem diagnosis of FES could be established only microscopically (Sudan III
      staining). Bronchopneumonia (24 cases), hyaline membranes (7 cases), as well as
      lung oedema and alveolar haemorrhages (in almost two thirds of the sample) were
      the most common microscopical findings in the lung as complications of FES. The
      most characteristic postmortem brain findings in FES are dotted perivascular
      haemorrhages, mostly in the white matter. These changes were not established in 7
      cases (surviving period was 1 to 2 days), but the especially stained sections
      pointed to FES as the cause of death. In addition to various chronic pathological
      changes, only intestinal haemorrhages and/or oedema of solid organs could be
      established microscopically. CONCLUSION: In the analyzed sample of 56 patients
      who died of FES, FES was clinically established onl

PMID- 10916461
TI  - [Bacterial vaginosis. Epidemiology and risk factors].
AB  - Bacterial vaginosis (BV) is a change in vaginal ecosystem where lactobacilli
      dominate, flora is absent or greatly reduced, and replaced with a mixed,
      predominantly anaerobic flora, consisting of Gardnerella vaginalis, Mycoplasma
      hominis, Mobiluncus spp, Bacteroides spp, Prevotela spp, Peptostreptococcus spp,
      Fusobacterium spp and Porphyromonas spp. The concentration of bacteria increases
      from 100 to 1000 fold in women with BV compared to healthy women. BV has been
      formerly known as nonspecific vaginitis, Haemophilus vaginitis, Corynebacterium
      vaginitis, Gardnerella vaginitis and anaerobic vaginintis. BV is the most
      prevalent form of vaginal disturbances in reproductive age women. The average
      incidence of BV varies: 10-35% in patients visiting gynaecological wards, 10-30%
      in patients visiting obstetric wards and 20-60% in patients visiting services of
      sexually transmitted diseases. A typical clinical symptom of BV is malodorous
      vaginal discharge. However, more than 50% of all women with BV are asymptomatic.
      BV has been associated with many gynaecological and obstetric complications such
      as cervicitis, salpingitis, endometritis, postoperative infections, urinary tract
      infections, pelvic inflammatory disease, mild abnormal Pap smear results and
      possible link with cervical intraepithelial neoplasia, preterm delivery,
      premature rupture of the membranes, chorioamnionitis and postpartum endometritis.
      Factors that increase the risk of BV are multiple partners, exposure to semen,
      prior trichomoniasis, intrauterine device usage, smoking, indigent population and
      frequent use of scented soap. Diagnosis of BV is established by Amsel's criteria
      of which three of four are the following: presence of homogeneous discharge,
      vaginal fluid pH > 4.5, positive amine test and microscopic analysis of Gram
      stained smear of vaginal discharge where "clue" cells (epithelial vaginal cells
      covered with mass of adherent bacteria, mostly coccobacilli) should be detected.
      The treatment of patients with BV consist of metronidazole or clindamycin, per os
      or intravaginally. The treatment of asymptomatic women and male sex partners of
      women with BV is controversial. The aim of the study was to establish the
      occurrence rate of BV in our women and potential factors increasing the risk of
      BV. We examined 166 women at the Institute of Microbiology and Immunology,
      University School of Medicine, Belgrade. Diagnosis of BV was established by
      Amsel's criteria. Each woman filled in a special questionnaire. Pregnant women
      were excluded. BV was diagnosed in 25% (33/166) of women. BV was more common
      among women with multiple partners. The most prevalent clinical symptom of BV was
      malodorous vaginal discharge. Vaginal symptoms became more evident after
      intercourse. Taking into consideration the occurrence rate of BV and its
      connection with numerous gynaecological and obstetric sequelae, and taking into
      account that the diagnosis of BV is quick, simple and inexpensive, we suggest
      that the examination of BV in women becomes a usual procedure.

PMID- 10916462
TI  - [Interaction of cells and the extracellular matrix in the mesangium].

PMID- 10916463
TI  - [The renin-angiotensin-aldosterone system and chronic renal insufficiency].

PMID- 10916464
TI  - [Prevention of nausea and vomiting after administration of cytotoxic drugs].

PMID- 10916465
TI  - [Transfusions using fresh frozen blood plasma].

PMID- 10916467
TI  - [Sensitive nose is not to be despised].

PMID- 10916466
TI  - [Prevention of twin collision using ultrasound in the first phase of labor].

PMID- 10916468
TI  - [Magnetic tomography--diagnostic imaging in future pediatrics?].

PMID- 10916469
TI  - [Practical training in medical education].

PMID- 10916470
TI  - [Clinical skills among interns].
AB  - BACKGROUND: Previous reports have demonstrated variable and partly insufficient
      skills levels in common practical procedures among interns after internship in
      hospital. The aim of the present study was to examine the development in interns'
      skills levels in practical procedures in relation to their gender, medical
      school, hospital and supervision. MATERIAL AND METHODS: Between July 1996 and
      July 1999 all interns in Norway were asked to indicate their skills level in 88
      practical clinical procedures before and after hospital internship. Of the 599
      interns included, 472 replied (79%). RESULTS: Males reported significant higher
      skills levels than females. After internship, no differences between interns
      graduated from the four universities were observed. Our study shows that the
      hospital internship is an important part of the medical education. An overall
      improvement was found in all interns. Interns whose skills levels were low before
      internship, had the best improvement. INTERPRETATION: The finding of a variable
      skills level before and a variable development during internship indicates that
      teaching in practical procedures is unstructured and inadequate. A consensus on
      the skills to be acquired and on what level is needed. Improvements are also
      needed in the quality of supervision.

PMID- 10916471
TI  - [Inscribed in the body].
AB  - BACKGROUND: Accumulated general practice experience from numerous encounters with
      sexually victimized persons motivated this study of childhood sexual abuse with
      regard to its longterm impact on life and health. THEORY, METHODS, AND MATERIAL:
      Phenomenology is its theoretical frame of references, and its methodological
      tools are hermeneutics, 34 adult users of two Norwegian incest centres consented
      to being interviewed in depth about their encounters with the health care system.
      The audiotaped interviews were transcribed verbatim. Relevant medical records
      filled out 16 of the interviews. Likewise, extensive field notes from interview
      setting were collected. RESULTS: The experiences linked to violation, illness and
      treatment clustered around seven phenomena present in every interview in at least
      one modality. These were termed sensory imprints, confused judgements,
      maladaptive adaptations, strained relationships, recognized memories, unheard
      messages, and reactivated experiences. INTERPRETATION: The impact of childhood
      sexual abuse was shown to transgress linear time, cause-effect relationship,
      categorical distinction and individuality. Since these four central preconditions
      for a correct medical judgement were not provided, harmful, though presumably
      correct, medical treatment was a frequent result. Consequently, the abused
      persons were revictimized in medical contexts when asking for help for sickness
      in the wake of socially silenced sexual violation.

PMID- 10916472
TI  - [High dose chemotherapy with autologous stem cell support in cancer patients].
AB  - INTRODUCTION: In 1996 it was decided that high-dose chemotherapy with peripheral
      stem cell support should be offered by all five university hospitals in Norway.
      MATERIAL AND METHODS: We report on the first 49 patients from the western part of
      Norway treated with this modality at Haukeland University Hospital in the 1996-98
      period. RESULTS: All patients had a total of > 2-10(6) CD34 positive cells/kg
      collected before high-dose chemotherapy. To achieve this critical stem cell dose,
      five patients had to have three or more stem cell collections; four of them had
      to be mobilised several times. Poor stem cell mobilisation was mostly marked in
      patients with soft tissue sarcoma and testicular cancer, but was also observed in
      a few heavily pre-treated patients with non-Hodgkins lymphoma. With the exception
      of one lymphoma patient who developed a rapid bone marrow relapse, all patients
      had satisfactory sign of bone marrow regeneration after reinfusion of the stem
      cells. This also applied to the poor mobilisors. No treatment-related deaths have
      occurred. Four to 38 months after high-dose therapy, 33% of patients with
      multiple myeloma and 52% of patients with malignant lymphoma were alive and in
      complete remission. Three of the four patients with soft tissue sarcoma relapsed
      3-7 months after high-dose chemotherapy.

PMID- 10916474
TI  - [Palindromic rheumatism].
AB  - BACKGROUND: Palindromic rheumatism is an inflammatory rheumatic disease
      characterised by recurrent attacks of arthritis confined to one or more
      peripheral joints. Each episode of arthritis rarely lasts more than 14 days, and
      subsides without leaving any residues. MATERIAL AND METHODS: Three patients with
      palindromic arthritis are presented, and the literature reviewed. RESULTS: The
      clinical and laboratory characteristics of the three patients were similar to
      those generally described for palindromic rheumatism. Two patients developed
      seropositive rheumatoid arthritis and one patient developed chronic seronegative
      polyarthritis. INTERPRETATION: Palindromic rheumatism may evolve into chronic
      polyarthritis.

PMID- 10916473
TI  - [Referrals from general practitioners to rheumatologists].
AB  - BACKGROUND: The study is an analysis of referrals of new patients from general
      practitioners to an outpatient clinic of rheumatology. MATERIAL AND METHODS: All
      referrals from general practitioners during a 12 months period were evaluated.
      RESULTS: The annual incidence of referrals of new patients was 423 per 100,000.
      The main cause of referral was diagnosis, and more than half of the diagnoses
      suggested were changed at the visit. Few of the referred patients had severe
      disease. INTERPRETATION: The selection of patients for specialist consultation in
      rheumatology should be changed in favour of patients with severe disease at the
      expense of those with long-standing non-debiliating disorders.

PMID- 10916475
TI  - [Topiramate--a new antiepileptic agents].
AB  - BACKGROUND: Topiramate is a novel antiepileptic drug that was licensed in Norway
      in 1997 as adjunctive treatment for patients with partial seizures. Metaanalysis
      of randomized controlled studies suggest that topiramate may be the most potent
      of the new antiepileptic drugs and have a favourable pharmacokinetic profile. At
      the National Center for Epilepsy we have used topiramate since 1990. We present
      our clinical experience with the drug. MATERIAL AND METHODS: We have,
      retrospectively, assessed 114 adult patients, mainly with intractable partial
      seizures, who received topiramate as add-on treatment. Average follow-up was 2.3
      years. RESULTS: Four patients (3.5%) became seizure free. The overall seizure
      frequency was reduced by > 50% in 56 patients (49%). Adverse effects were
      observed in 82 patients (72%); in 54 patients (47%) the drug had to be withdrawn
      due to unacceptable side effects and/or lack of clinical effect. The most
      frequent side effects were weight loss, fatigue, behavioural and cognitive
      problems. INTERPRETATION: Our results corroborate an impression of topiramate
      being an effective drug used as adjuntive therapy in patients with refractory
      epilepsy. Side effects can be a problem, but a low starting dose, a slow dose
      escalation, and topiramate used alone may reduce this problem.

PMID- 10916476
TI  - [Metformin associated lactic acidosis--case reports and literature review].
AB  - BACKGROUND: The use of metformin in the treatment of diabetes mellitus type II is
      increasing. The drug has several advantageous metabolic effects, and is
      considered safe if not used in the presence of contraindications, in particular
      renal failure. MATERIAL AND METHODS: We present a patient with metformin
      associated lactic acidosis, to remind of a potentially lethal adverse reaction.
      We also review the literature about incidence and risk, prognosis and treatment
      of the disease. RESULTS: Our patient was a 72 year old woman with diabetes
      mellitus type II treated with metformin, who presented with acute renal failure,
      severe metabolic acidosis and circulatory failure. Treatment with bicarbonate
      buffer and vasopressors did not improve her condition, only after hemodialysis
      was her situation stabilised. INTERPRETATION: Metformin associated lactic
      acidosis must be considered in obscure metabolic acidosis in diabetic patients.
      The single most important therapeutic approach appears to be immediate
      hemodialysis.

PMID- 10916477
TI  - [Natural killer cells--important in the immunologic defense].
AB  - Natural Killer (NK) cells are a group of lymphocytes with a characteristic
      morphology and function. They are abundant in blood, spleen, liver and lungs.
      They are distinct from both T and B lymphocytes in their circulation patterns,
      profile of surface antigens, receptor repertoire and the way they discriminate
      between self and nonself. This latter NK function can partly be explained by an
      array of recently characterised NK receptors that can recognise and accurately
      discriminate between normal and altered MHC class I determinants. The basis for
      this discrimination is different from that of T cells and is discussed in this
      article. The role of NK cells in antimicrobial defense is well demonstrated,
      particularly that against viruses belonging to the herpesvirus group. A case
      report of a patient with a selective defect in NK cells and with recurrent viral
      infections is described. The role of NK cells in defense against malignant cells
      is more circumstantial, but NK cells do possess receptors which recognise tumour
      cells and kill them efficiently in vitro. A receptor which can recognise
      determinants unique for cancer cells has recently been described.

PMID- 10916478
TI  - [Methemoglobinemia--causes, diagnosis and treatment].
AB  - BACKGROUND: Methaemoglobinaemia is an infrequent condition. It can be congenital
      or be induced by several toxic compounds. In methaemoglobin (metHb) the iron in
      the haem moiety of haemoglobin is oxidized from the ferrous (Fe2+) to the ferric
      state (Fe3+). This complex is dark brown and unable to transport oxygen. Combined
      with a leftward shift in the oxyhaemoglobin dissociation curve this leads to
      decreased tissue oxygenation with subsequent hypoxic features in patients. CASE
      REPORTS: We report two cases of dapsone-induced methaemoglobinaemia. The blood,
      mucosa and nail beds adopted a brown-bluish appearance which was used
      diagnostically. One patient was treated effectively with repeated injections of
      methylene blue, which reduces methaemoglobin. In the other patient, the
      methaemoglobin level declined with a T50 of 50 hours. Both patients had few
      symptoms and made an uneventful recovery. INTERPRETATION: The hypoxia in
      methaemoglobinaemia may be effectively treated with methylene blue. Repeated
      injections may be necessary.

PMID- 10916479
TI  - [Magnetic tomography--new imaging techniques and future perspectives].
AB  - BACKGROUND: MRI is a promising imaging technique for diseases in most organ
      systems in children. MATERIAL AND METHODS: This review discusses MRI on the basis
      of the literature and our own experience. RESULTS: The value of MRI in paediatric
      neuroradiology is firmly established. In congenital heart defects and other
      reasons for cardiovascular imaging in children, the non-invasiveness of the
      method is appealing. MRI is already included in most international paediatric
      oncology protocols. Paediatric applications for MRI differ from those in adults
      as they focus on developmental and congenital abnormalities. Furthermore, some
      pathological conditions are unique to children. MRI is also a promising
      alternative to established methods for evaluation of the urinary tract. There are
      some specific problems with MRI in children. Immobilisation and sedation
      techniques include tight wrapping of the newborn with soft elastic bands, feeding
      immediately prior to the study, and allowing one parent into the magnet with the
      child. Midazolam and oral chloral hydrate are usually used for sedation.
      INTERPRETATION: MRI is of particular value in the paediatric age group as the
      method is capable of highly accurate imaging in a variety of congenital and
      paediatric diseases without the use of ionising radiation. Faster sequences and
      better resolution will further increase the use of MRI in children.

PMID- 10916480
TI  - [Magnetic tomography--new imaging techniques and future perspectives].
AB  - BACKGROUND: From the very introduction of MRI into medicine, the modality has
      presented the user a long list of theoretical tissue contrast parameters. The
      development of MRI has been aimed at turning these theoretical possibilities into
      practical options. MATERIAL AND METHODS: We give an overview of the new MRI
      techniques and perspectives for the future based on a literature search and our
      own experience. RESULTS: Today, the modality offers state-of-the-art anatomical
      details as well as visualisation of several functional parameters such as
      perfusion, diffusion, blood oxygen saturation, and tissue temperature. In the
      near future, MRI may provide absolute quantification of regional perfusion and
      rate of oxygen consumption in a clinical setting. New vascular and
      gastrointestinal contrast media will further increase the sensitivity and
      specificity of MRI. A continuous increase in imaging speed has made MRI capable
      of providing adequate "fluoroscopic" guidance during interventional procedures,
      and real-time diagnostic imaging is only few years ahead. INTERPRETATION: The
      spread of MRI installations will increase as a result of increasing demand for
      the best and least harmful diagnostic procedure. The main challenge to the MRI
      community will be to exploit the vast diagnostic possibilities.

PMID- 10916482
TI  - [Problems with internship].

PMID- 10916481
TI  - ["Free" hospitals--market ethics before professional and society's ethic].

PMID- 10916483
TI  - [Every Norwegian will soon become a physician--a quick course on scenario
      research].

PMID- 10916484
TI  - [Check list in the treatment of acute myocardial infarction with thrombolytics
      and other drugs].

PMID- 10916485
TI  - [Is thrombolytic therapy efficient in stroke?].

PMID- 10916486
TI  - [Oral contraceptives and thrombosis--what was written in the Tidsskrift and
      when?].

PMID- 10916487
TI  - [Psychiatric treatment--from belief to science? Reason for psychiatric
      treatment].

PMID- 10916488
TI  - [On beliefs and science in psychiatric treatment].

PMID- 10916489
TI  - [The basis for psychiatric treatment--rhetorics in scientific clothes?].

PMID- 10916490
TI  - [A deep-drawn sigh from a radiologist in private practice].

PMID- 10916491
TI  - [Continuing education supported by sponsors?].

PMID- 10916492
TI  - [Viewpoint. The new infection protection law--a help or a hurdle?].

PMID- 10916493
TI  - [Diabetic retinopathy and associated risk factors in type-1 and type-2 diabetics
      in the Upper Palatinate].
AB  - BACKGROUND AND OBJECTIVE: Diabetic retinopathy is the main cause of blindness in
      industrial countries. This study was undertaken to determine the prevalence of
      diabetic retinopathy and risk indicators among volunteers in a rural district in
      Bavaria, Germany. PATIENTS AND METHODS: Using a mobile survey unit, we
      investigated 627 diabetic volunteers (275 women, 352 men, mean age 64.5 +/- 12.5
      yr) in 23 cities and villages. One retinal Polaroid photo was taken per eye,
      using a non-mydriatic camera (Canon CR4-45 NM). RESULTS: In 60 subjects (9.6%)
      retinal photographs were not assessable. Among the remaining 567 patients (76
      type-1 diabetes, HbA1c 7.3 +/- 1.2% and 491 type-2 diabetes, HbA1c 7.7 +/- 1.5%)
      in 72.3% no retinopathy was found (57.9% type-1 diabetes/74.5% type-2 diabetes).
      Non-proliferative retinopathy was diagnosed in 22% (38.2%/19.6) and proliferative
      retinopathy in 5.6% (3.9%/5.9%). Photocoagulation scars were present in 6.1%
      (11.7%/5.3%) and macular oedema in 11.8% (14.1%/11.6%). In 6.1% (5.3%/6.6%) of
      patients visual acuity was less than 0.1 in at least one eye. The degree of
      retinopathy was found to be related to the duration of diabetes mellitus, age at
      onset, glycaemic control (HbA1c), blood pressure and symptoms of neuropathy.
      CONCLUSIONS: The prevalence of retinopathy of 22.0% in the study group was found
      to be low for non-proliferative diabetic retinopathy, perhaps due to the methods
      used and/or good or acceptable glycaemic control measured as HbA1c.

PMID- 10916494
TI  - [The value of bronchoalveolar lavage in the clarifying of HIV-associated lung
      diseases].
AB  - BACKGROUND AND OBJECTIVE: Examination of sputum is the first diagnostic step in
      the evaluation of HIV-infected patients with pulmonary complications. We were
      interested in the indications and the diagnostic value of subsequent bronchoscopy
      and bronchoalveolar lavage (BAL) and especially the importance of so-called
      atypical bacteria. PATIENTS AND METHODS: We analysed 59 consecutive BALs
      performed in HIV positive patients with pulmonary symptoms (48 men, 11 women, age
      22-70 years, 36 in stage C). Culture for Legionella pneumophila and PCR analysis
      for Mycoplasma pneumoniae and Chlamydia pneumoniae were done in all cases.
      RESULTS: In 50 patients (85%) there was a clear indication for performing a BAL
      because either an infectious agent could no be detected on sputum examination (n
      = 36), or the patient's sputum production was insufficient (n = 14). In 30 (60%)
      of these cases bronchoscopy and BAL were able to establish a diagnosis. The most
      frequent agent was Pneumocystis carinii (n = 12). In contrast, BAL was able to
      establish coinfection in patients with positive sputum samples in one case only.
      So-called atypical bacteria were not found. CONCLUSION: In patients with a clear
      indication, especially a non-diagnostic sputum examination, BAL plays an
      important role in the work-up of HIV-associated pulmonary disease. The search for
      so-called atypical bacteria yields unsatisfactory results.

PMID- 10916495
TI  - [Brain infarct from a paradoxical embolism following a varices operation].
AB  - HISTORY AND CLINICAL FINDINGS: A 70-year-old woman developed an acute right-sided
      hemiparesis and global aphasia 10 days after saphenous vein stripping of
      varicosities. Initially, she presented with somnolence, conjugated to the left,
      flexor synergism of the right extremities, exaggeration of knee and ankle jerks
      and extensor plantar responses on the right side. INVESTIGATIONS: The initial
      cranial computed tomography one hour after the onset of symptoms did not show
      reliable signs of cerebral ischaemia but a "dense artery sign" of the left middle
      cerebral artery. Repeat computed tomography then revealed a partial, mainly
      subcortical, infarction of the left middle cerebral artery territory. Doppler
      sonography revealed an occlusion of the left internal carotid artery. In duplex
      sonography there was no evidence of arteriosclerosis. Transesophageal
      echocardiography revealed a patent foramen ovale with right-to-left shunt.
      TREATMENT AND COURSE: Immediately after admission intravenous anticoagulation was
      initiated because of the suspected cardioembolic origin of the stroke. During
      hospitalization the global aphasia regressed and a continuing mobilization was
      achieved while the right-sided hemiparesis persisted. The neurological
      rehabilitation was initiated and continuous oral anticoagulation was planned.
      CONCLUSION: This case suggests a causal relationship between previously performed
      vein stripping and paradoxical embolism resulting in a stroke. For patients with
      patent foramen ovale, vein stripping may be associated with an increased stroke
      risk.

PMID- 10916496
TI  - [Asymptomatic diclofenac-induced acute hepatitis].
AB  - HISTORY AND ADMISSION FINDINGS: After removal of an herniated intervertebral disc
      a 49-year-old man had recurrent pain in the lumbar region, treated with
      diclofenac and flupirtine. 4 months postoperatively he was referred to the
      author's hospital because of progressive rise in transaminase levels and in
      cholestasis parameters. Physical examination on admissions was unremarkable,
      except for jaundice. INVESTIGATIONS: Laboratory tests showed an increases in
      transaminases (GPT 769 U/l [normal: < 23 U/l], GOT 285 U/l [normal: < 19 U/l])
      and in cholestasis-related values (gamma-GT 172 U/l [Norm 6-28 U/l], alkaline
      phosphatase 207 U/l [normal < 175 U/l], total bilirubin: 2.5 mg/dl [Norm < 1.1
      mg/dl]). This corresponded to the histological finding of toxic damage to the
      liver parenchyma. Viral, autoimmune and metabolic causes had been excluded.
      DIAGNOSES, TREATMENT AND COURSE: The history as well as laboratory and
      histological findings indicated diclofenac-induced toxic hepatitis. The drug was
      discontinued and without any treatment all laboratory values returned to normal
      within 9 weeks. CONCLUSION: Diclofenac, a frequently prescribed non-steroid anti
      inflammatory drug, is generally thought to be relatively safe. But it can produce
      toxic hepatitis which may be asymptomatic (but this patient was jaundiced) and
      may take an unforeseeable course. This should be taken account of by regularly
      monitoring liver functions.

PMID- 10916497
TI  - [Proteomics].

PMID- 10916498
TI  - [The endoscopic positioning of tube systems (PEG/PEJ tubes) for enteral feeding].

PMID- 10916499
TI  - [Association and linkage studies for the analysis of candidate genes].

PMID- 10916500
TI  - The numbers game.

PMID- 10916501
TI  - Wide-complex tachycardia in a young man.

PMID- 10916502
TI  - Rectal bleeding, abdominal pain, and fever.

PMID- 10916503
TI  - Genetics in practice: 2. Colon and breast cancer.
AB  - Those who test negative should be reminded that normal risk does not mean no
      risk, and standard cancer screening guidelines should still be followed. In
      patients with a strong family history of risk, a negative genetic test result
      indicates reduced risk only if a specific mutation has been identified in other
      family members.

PMID- 10916504
TI  - Chronic pain: 1. A new disease?
AB  - Chronic pain continues to be perceived as a characterologic disorder rather than
      a serious, potentially fatal, medical disease. The general lack of understanding
      of how persistent pain becomes magnified and ingrained prevents many patients
      from receiving the level of care that they need to regain control of their lives
      and resume normal activities.

PMID- 10916505
TI  - A simple therapeutic combination for type 2 diabetes.
AB  - When oral agents alone can no longer provide adequate glycemic control, the
      combination of a single bedtime injection of insulin with two daily doses of
      metformin will often normalize blood glucoses levels without the weight gain and
      hypoglycemia that may occur with other combined regimens.

PMID- 10916506
TI  - Managing psychiatric disorders in primary care: 2. Anxiety.
AB  - Most anxious patients are first seen and treated by primary care physicians.
      Treatment is generally long-term, and often the results are not what either
      patient or physician would regard as optimal. Nevertheless, timely and
      appropriate intervention can markedly improve function--it may make the
      difference between a generally satisfying life and one lived in fear and
      isolation.

PMID- 10916507
TI  - Current treatment options in psoriasis.
AB  - Much has been learned about the pathophysiology of psoriasis during the last
      decade, and as a result, traditional treatments such as coal tar have been joined
      by immunosuppressive agents. Patients can be offered a variety of therapies keyed
      to the type and severity of disease.

PMID- 10916509
TI  - NetWellness: utilizing a consumer health information web site to access nutrition
      professionals.

PMID- 10916510
TI  - High-protein, low-carbohydrate diets: do they work?

PMID- 10916511
TI  - MNT essential to plans for adding prescription drug benefit to Medicare.

PMID- 10916512
TI  - Fluid needs of older adults.

PMID- 10916513
TI  - The 2000 Dietary Guidelines for Americans: what are the changes and why were they
      made? The Dietary Guidelines Advisory Committee.

PMID- 10916514
TI  - Accuracy in dietary assessment: on the road to good science.

PMID- 10916515
TI  - In-person vs telephone-administered multiple-pass 24-hour recalls in women:
      validation with doubly labeled water.
AB  - OBJECTIVE: To determine the accuracy of energy intakes estimated with the
      multiple-pass 24-hour recall method in women by conducting in-person and
      telephone interviews. Doubly labeled water measurements of total energy
      expenditure were used for validation. SUBJECTS: Thirty-five weight-stable women
      (mean age = 30 years, range = 19 to 46 years) participated. DESIGN: Total energy
      expenditure was measured over a 14-day period using the doubly labeled water
      method. During this time, 4 multiple-pass 24-hour recalls were obtained from the
      women (2 in-person, 2 by telephone) who were provided 2-dimensional food models
      to estimate portion sizes. The Food Intake Analysis System was used to analyze
      recall data. STATISTICAL ANALYSES: Paired t tests were conducted to examine
      differences between energy intake estimated from the telephone and in-person
      interviews. Agreement between the energy intake estimates from the telephone
      recalls and the in-person recalls was assessed using the technique of Bland and
      Altman. Paired t tests were used to compare energy intake estimated from the
      telephone and in-person recalls to total energy expenditure. RESULTS: No
      significant difference in mean daily energy intake was found between the
      telephone (2,253 +/- 688 kcal) and in-person (2,173 +/- 656 kcal) interviews (P =
      .36). However, the mean energy intake from each interview method was
      significantly lower than total energy expenditure (2,644 +/- 503 kcal) (P = .006
      and .001, respectively). APPLICATIONS/CONCLUSIONS: Underreporting of energy
      intake was widespread in the sample. Although the multiple-pass 24-hour recall
      method did not generate a group measure of energy intake that was accurate or
      unbiased, the telephone-administered multiple-pass 24-hour recall was just as
      effective in estimating energy intake as the recall administered in-person.
      Dietetics professionals should be aware of the pervasive and serious problem of
      under-reporting of self-reported food intakes.

PMID- 10916516
TI  - Obesity prevalence by age group and 5-year changes in adults residing in rural
      Wisconsin.
AB  - OBJECTIVE: To estimate the prevalence of overweight and obesity and weight
      changes over a 5-year period in a rural adult population by age group. SUBJECTS:
      Residents of Marinette County, Wis: 613 women and 352 men. METHODS: Age, body
      weight, and height data were collected during October and December 1997 in a
      volunteer convenience sample of white men and women (aged 20 to 74 years). Age
      groups in 10-year increments were defined by age in 1992. Weights obtained from
      medical and employment records from 1992 by medical personnel, as well as self
      reported weights, were recorded for 1992 to assess weight changes from 1992 to
      1997. RESULTS: In 1992 women and men had mean body weights of 72.1 and 88.4 kg,
      respectively. By 1997, the average weight for women in the same data set was 79.3
      and that for men was 96.4 kg, a gain of 7.3 and 7.9 kg, respectively. For both
      women and men, those in the youngest age group (age 20 to 30 years) experienced
      the greatest 5-year increase in body weight: 11.0 and 12.1 kg, respectively; the
      next largest increase occurred in the second youngest group (age 30 to 40 years).
      The majority of the normal-weight subjects (58%, 229 of 393) moved into an
      overweight or obese category, the overweight and obese generally gained weight,
      and only 20 of 572 overweight or obese individuals moved from an unhealthful to a
      healthful body weight during the 5 years. APPLICATIONS/CONCLUSIONS: The data
      indicate a need for community-wide weight-gain prevention programs for young
      adult men and women in rural areas. Weight-reduction treatment programs should be
      geared toward older adults, as most have already attained an unhealthful weight,
      which is likely to increase.

PMID- 10916517
TI  - A new recommendation for maternal weight gain in Chinese women.
AB  - OBJECTIVE: To characterize the distribution of maternal weight gain in Chinese
      women living in a well-nourished community, to recommend target weight gains from
      quartile values derived from women with good pregnancy outcomes, and to quantify
      the risk for adverse pregnancy outcomes encountered among subjects with weight
      gain outside these recommendations. DESIGN: A retrospective study on maternal
      anthropometry and pregnancy outcomes was conducted among Chinese women who
      delivered a singleton pregnancy in a university hospital in Hong Kong. SUBJECTS:
      Nine hundred eight women who delivered during the study period were identified.
      Among them, 754 (83%) had complete anthropometry data. The normative distribution
      of maternal weight gain was derived from 504 women who had a good pregnancy
      outcome. STATISTICS: Analysis of variance was used to compare total weight gain
      among women of different prepregnancy weight. Fisher exact test was used in the
      univariate analysis of the association between risk factors and corresponding
      adverse pregnancy outcomes. Adjusted odds ratios for adverse outcomes were
      determined by multiple logistic regression models controlling for the following
      factors: maternal age, duration of gestation, prepregnancy body mass index (BMI),
      height, parity, and smoking. RESULTS: A maternal weight-gain chart and
      recommendations for total weight gains in Chinese women were derived from the
      distribution of weight gain in subjects with good pregnancy outcomes. The
      recommended total weight gain was 13 to 16.7 kg, 11 to 16.4 kg, and 7.1 to 14.4
      kg respectively for women of low (BMI < 19), moderate (BMI: 19 to 23.5), and high
      (BMI > 23.5) prepregnancy BMI. Women who did not achieve the lower quartile value
      had more than twice the risk of having low-birth-weight infants. Those with
      excessive weight gain were at risk for needing assisted delivery. APPLICATIONS:
      As maternal anthropometry differs across ethnic groups, different recommendations
      should be made for specific populations.

PMID- 10916518
TI  - Impact of a camp experience on phenylalanine levels, knowledge, attitudes, and
      health beliefs relevant to nutrition management of phenylketonuria in adolescent
      girls.
AB  - OBJECTIVE: To evaluate the effectiveness of an education intervention in a summer
      camp setting on knowledge, attitudes, and health beliefs regarding metabolic
      control of phenylketonuria and dietary compliance. DESIGN: An observational study
      of a weeklong metabolic camp for adolescent girls with phenylketonuria (PKU) who
      were followed up over the course of 1 year. Observations also were made in 3
      subsequent years of camp. INTERVENTION: The camp experience consisted of diet and
      disease education, sessions on reproductive development, and recreation. Group
      discussions on attitudes and perceptions about PKU related to dietary compliance
      were held with nutritionists and a pediatric psychologist. OUTCOME MEASURES:
      Biochemical and psychological data were collected on the first and last days of
      the camp to assess short-term effects of the intervention, then at quarterly
      intervals during the year to determine the long-term impact of the camp. Precamp
      and Postcamp plasma amino acid data for the subsequent 3 years were also
      collected. SUBJECTS/SETTING: Analyses were based on 13 adolescent girls with PKU
      in the first year of a camp at Emory University in Atlanta, Ga, and compared with
      data from 11 additional campers enrolled the second year, 8 in the third year,
      and 7 in the fourth year. Mean age +/- standard deviation of first-year campers
      was 13 +/- 2 years, mean IQ +/- standard deviation was 98 +/- 16, and 9 of 13
      girls had menstruated. STATISTICAL ANALYSES PERFORMED: Short-term effects of the
      intervention were computed by comparing mean levels of response from the baseline
      period to those from the last day of camp using t tests for dependent samples.
      Repeated-measures analysis of variance was used to assess the long-term effects
      of the camp experience over the course of a year at regular quarterly intervals.
      RESULTS: Short-term effects of the education intervention were significant
      reductions in dietary phenylalanine intake, plasma phenylalanine levels, and
      perceived isolation. However, these effects progressively returned to baseline
      levels over the course of a year. The significant short- and long-term effects of
      increased knowledge of diet and disease persisted throughout the study period.
      APPLICATIONS/CONCLUSIONS: Short-term effects of the education intervention
      resulted in improved metabolic control associated with improved attitudes,
      increased knowledge of diet and disease, increased perceived support, and
      decreased barriers to dietary compliance in a camp setting.

PMID- 10916519
TI  - Use of a supermarket shelf-labeling program to educate a predominately minority
      community about foods that promote heart health.
AB  - OBJECTIVE: The purpose of this study was to evaluate the awareness and use of a
      supermarket-shelf labeling program designed to encourage shoppers to make food
      choices that promote heart health. DESIGN: A shelf-labeling program was
      implemented in 18 supermarkets serving minority communities in Detroit, Mich.
      Customers were given an exit survey to determine awareness and use of the
      program. SUBJECTS/SETTING: Three hundred sixty-one subjects were sampled. Sixty
      six percent of the sample was female, 67% African-American, and the sample
      population had a mean age of 51.6 years +/- 18.5 SD. RESULTS: Overall awareness
      of the program was 28.8%. Awareness among minorities was significantly higher
      when compared with whites (35.3% vs 20.8%; P = .02). Gender, age, and education
      level were not predictive of program awareness but people screened for
      cardiovascular disease risk factors (elevated low-density lipoprotein or total
      cholesterol levels and/or elevated blood pressure) in the previous year had
      greater awareness than those not screened (32.6% vs 13.6%, P = .06). Use of the
      program was 56% among subjects aware of the program. This did not differ
      significantly by gender, age, or ethnicity. STATISTICAL ANALYSIS: Awareness and
      use were evaluated with respect to ethnicity, gender, education, race, age, and
      previous screening history. For purposes of analysis, African-American, Hispanic,
      and Asian-American respondents were combined into one group called "all
      minorities." The other group of respondents was called "whites." Between-group
      differences in categorical variables were analyzed using a chi 2 statistic.
      CONCLUSIONS: Awareness of the shelf-labeling program was modest, but highest
      among African-Americans. Subjects recently screened for cardiovascular disease
      risk had greater program awareness. This difference was not statistically
      significant. Use was relatively high among those aware of the program, suggesting
      that shelf labels have the potential to increase the selection of foods that
      promote heart health in predominately low-income, minority populations.

PMID- 10916521
TI  - Applying conversation analysis to foster accurate reporting in the diet history
      interview.
AB  - Inaccuracy in reporting dietary intakes is a major problem in managing diet
      related disease. There is no single best method of dietary assessment, but the
      diet history lends itself well to the clinical setting. In many diet histories
      data are collected orally, so analysis of interviews can provide insights into
      reporting behaviors. Conversation analysis is a qualitative method that describes
      the systematic organization of talk between people. Patterns are identified and
      checked for consistency within and among individual interviews. The aim of this
      study was to describe consistent ways of reporting diet histories and to identify
      conversational features of problematic reporting. Diet history interviews from 62
      overweight and insulin-resistant adult volunteers (50 women, 12 men) attending an
      outpatient clinic and 14 healthy volunteers (7 men, 7 women) participating in an
      energy balance study were audiotaped and transcribed. Conversation analysis
      identified a remarkably consistent pattern of reporting diet histories and 3
      conversational features that indicated problematic reporting: "it depends,"
      denoting variability (least of all at breakfast); "probably," suggesting
      guesswork (related to portion sizes); and elaborated talk on certain foods,
      distinguishing sensitive topics (e.g., alcohol, chocolate, butter/margarine, take
      out foods) from safe topics. These findings indicate that there are ways in which
      dietetics practitioners may conduct the diet history interview to foster more
      accurate reporting.

PMID- 10916520
TI  - Effects of increased consumption of fluid milk on energy and nutrient intake,
      body weight, and cardiovascular risk factors in healthy older adults.
AB  - OBJECTIVE: To assess the impact of increased consumption of milk, without other
      dietary advice, on older adults' energy and nutrient intakes, weight,
      cardiovascular risk factors (blood pressure, plasma lipid levels), and quality of
      life. SUBJECTS/SETTING: Two hundred four healthy men and women, aged 55 to 85
      years, who consumed fewer than 1.5 dairy servings per day were chosen from six US
      academic health centers. DESIGN: Randomized, controlled open trial. INTERVENTION:
      Advice to increase skim or 1% milk intake by 3 cups per day (n = 101) or to
      maintain usual diet (n = 103) for 12 weeks after a 4-week baseline period. MAIN
      OUTCOME MEASURES: Changes in energy and nutrient intake assessed from 3-day food
      records, body weight, blood pressure, and plasma lipid levels. STATISTICAL
      ANALYSES PERFORMED: Group-by-time analysis of variance with repeated-measures,
      chi 2 test. RESULTS: Compliance with the intervention was good. Compared with
      controls, participants in the milk-supplemented group significantly increased
      energy, protein, cholesterol, vitamins A, D, and B-12, riboflavin, pantothenate,
      calcium, phosphorus, magnesium, zinc, and potassium intakes. Prevalence of
      nutrient inadequacy, assessed for nutrients with Estimated Average Requirements,
      decreased among women in the milk group for magnesium (40% at baseline vs 13% at
      12 weeks, P < .001) and vitamin B-12 (6% vs 0%, P < .05) and tended to decrease
      (P < .10) for protein and thiamin (women) and magnesium and vitamin B-6 (men).
      The milk group gained 0.6 kg more than control group (P < .01); however, weight
      gain was less than predicted, which suggests some compensation for the added
      energy from milk. Blood pressure decreased similarly over time in both groups.
      Total and low-density lipoprotein cholesterol levels, and the ratio of total
      cholesterol to high-density lipoprotein cholesterol, were unchanged. Triglyceride
      levels increased within the normal range in the milk group (P = .002). Quality of
      life scores were high at baseline and remained high throughout.
      APPLICATIONS/CONCLUSIONS: Older adults can successfully increase milk intake,
      thereby meaningfully improving their nutrient intakes. Dietitians can play a key
      role in disseminating this advice.

PMID- 10916522
TI  - Evaluation of WHO and NHANES II standards for overweight using mortality rates.

PMID- 10916523
TI  - Behavioral strategies to increase fruit and vegetable intake by fourth- through
      sixth-grade students.

PMID- 10916524
TI  - Acceptability of oatmeal chocolate chip cookies prepared using pureed white beans
      as a fat ingredient substitute.

PMID- 10916525
TI  - Dietary patterns among members of the Catawba Indian nation.

PMID- 10916526
TI  - Nutrition composition of emu compares favorably with that of other lean meats.

PMID- 10916527
TI  - Joint Commission on Accreditation of Healthcare Organizations: friend, not foe.

PMID- 10916528
TI  - [Diagnosis of malnutrition in the elderly by dual energy absorptiometry].
AB  - OBJECTIVES: Denutrition is a frequent condition in elderly persons and may have
      major consequences. A noninvasive investigation, whole body dual energy X-ray
      absorptiometry, should allow, by direct measurement of body composition, early
      and reliable diagnosis of denutrition. This study was conducted to elaborate a
      diagnostic tool using this exam and to test its validity. PATIENTS AND METHODS: A
      global index of denutrition was proposed combining anthropometric, biological
      criteria, and the Mini Nutritional Assessment scale. Two agreement analyses were
      made between classical diagnostic criteria of nutritional status and body fat and
      fat free mass assessed by anthropometry and absorptiometry. An association
      between nutritional status and body absorptiometric composition were studied with
      univariate analysis followed by a multivariate logistic regression model. This
      model allowed an elaboration of a nutritional absorptiometric index (NAI).
      RESULTS: One hundred one elderly subjects were included. Twenty-three were
      considered to be in a state of denutrition. Agreement was poor between
      anthropometric and biological diagnostic criteria of denutrition. It was good
      between the different masses assess by anthropometry and absorptiometry. Subjects
      in a state of denutrition had significantly lower body fat and lower fat free
      mass. The fat free mass index (fat free mass divided by the square height) and
      body fat were entered into a logistic model and composed the NAI, which showed
      good diagnostic validity in terms of specificity and sensitivity. DISCUSSION:
      Absorptiometry appears to be a simple reliable diagnostic tool for assessing
      denutrition in elderly persons in routine practice. Further studies are required
      and should lead to a confirmation of the interest of these absorptiometric
      indexes.

PMID- 10916529
TI  - [Evaluation of the hypothalamo-hypopituitary axis after long-term inhalation
      corticotherapy for nasal polyposis].
AB  - OBJECTIVE: To assess the hypothalamic-pituitary-adrenal (HPA) axis after long
      term intranasal corticosteroid treatment in nasal polyposis. PATIENTS AND
      METHODS: A short synacthen test was performed in 24 patients who received the
      highest dose of inhaled beclomethasone among a population of 392 patients treated
      for nasal polyposis with inhaled corticosteroid therapy and short-term oral
      corticosteroids. RESULTS: Mean yearly dose of oral prednisone administered in
      short-term treatment was 371 mg/year. The amount of short-term oral prednisone
      decreased during the treatment. Mean daily dose of inhaled beclomethasone was
      2861 micrograms/day, decreasing during treatment. Morning plasma cortisol was
      normal in all patients before and after stimulation (163 +/- 44 and 1 +/- 60
      micrograms/ml respectively). Nolomethasone dose and plasma cortisol level before
      or after stimulation. DISCUSSION: The high dose of inhaled beclomethasone used to
      treat nasal polyposis does not affect the HPA axis. Some authors in the
      literature contest the validity of short synacthen test to detect HPA axis
      suppression. This test does however detect severe impairments of the HPA axis in
      outpatients.

PMID- 10916530
TI  - [Gamstorp's disease in a Marseilles family].
AB  - BACKGROUND: Primary periodic palsy is a group of muscular diseases transmitted by
      autosomal dominant inheritance. The characteristic features are flaccid muscular
      deficiency, abolition of reflexes, and dyskalemia. CASE REPORT: A 36-year-old
      woman presented a 5-year history of acute episodes of myalgia, muscle
      contracture, and muscle paralysis involving first the hand, then all four limbs
      and the face, sparing the respiratory muscles. The symptoms totally regressed
      spontaneously within one hour or in a shorter time if the patient ingested sugar.
      Demonstration of hyperkalemia during an acute episode led to the diagnosis of
      transfer hyperkalemia typical of Gamstorp's disease. Several members of the
      family presented identical symptoms. DISCUSSION: Despite progress in our
      understanding of this disease, diagnosis is often made late. The diagnostic
      strategy is however quite simple: serum potassium during an acute episode and
      provocation test with fasting and rest.

PMID- 10916532
TI  - [Liposarcoma of the thigh: 20-year development].

PMID- 10916531
TI  - [Acute dissection of the ascending thoracic aorta complicated by myocardial
      infarct: an unavoidable diagnostic pitfall?].
AB  - BACKGROUND: Acute dissection of the aorta during myocardial infarction is
      exceptional. In such cases, fibrinolysis can be fatal. CASE REPORTS: A 63-year
      old woman with a history of hypertension was referred to our intensive care unit
      with the diagnosis of early stage inferior myocardial infarction. Thrombolysis
      was instituted and the patient rapidly developed cardiovascular collapse with
      global heart failure. Coronarography was attempted to revascularize the occluded
      coronary artery but the coronary arteries could not be catheterized. An
      aortography was performed and gave the diagnosis of De Bakey type I dissection of
      the aorta. The patient died from cardiac arrest after a phase of low cardiac
      output. DISCUSSION: This case illustrates how myocardial infarction can
      complicate or mask acute dissection of the aorta. It also raises the question of
      transthoracic echocardiography prior to institution of fibrinolysis.

PMID- 10916533
TI  - [A new bisalbuminemia: bisalbuminemia of Kenitra].

PMID- 10916534
TI  - [Endoscopic treatment of diverticular hemorrhage].

PMID- 10916535
TI  - [Compliance with antiretroviral therapy: the psychological dimension].

PMID- 10916536
TI  - [Right heart insufficiency due to thiamine deficiency].

PMID- 10916537
TI  - [Prevention of cardiovascular disease in the elderly].
AB  - PREVENTION OF STROKE: Several preventive strategies have been found to be
      effective for the prevention of stroke in elderly subjects, including treatment
      of high blood pressure, oral anticoagulants in case of atrial fibrillation,
      aspirin for subjects at risk. PREVENTION OF MYOCARDIAL INFARCTION: Anti
      hypertension treatment and aspirin for at risk subjects have been proven
      effective. For elderly subjects who have had a myocardial infarction, beta
      blockers and converting enzyme inhibitors are effective in case of altered left
      ventricular function. The importance of lowering cholesterol levels in the
      elderly is a subject of debate. In coronary artery disease patients, at least up
      to the age of 75 years, statins can reduce the risk of a coronary event and
      stroke. GENERAL MEASURES: Exposure to tobacco smoke and sedentary lifestyle are
      associated with increased cardiovascular risk in the elderly. Stopping smoking
      and regular physical exercise should be advised for the elderly. The
      cardiovascular benefit of hormone replacement therapy after menopause is not
      clearly established and is the object of ongoing research.

PMID- 10916538
TI  - [The preventive effects of physical activity in the elderly].
AB  - PHYSICAL ACTIVITY AND AGING: Physical activity prevents some age-related
      impairment. Physical activity reduces the decline of physical capacity which
      remains limited by maximal heart rate, and reduces the incidence of
      cardiovascular diseases by decreasing and preventing associated risk factors.
      Physical activity reduces age-related bone loss, its effect being potentialized
      by hormonal replacement therapy, and improves balance function, leading to a
      lower incidence of falls and fractures in older subjects. Physical activity helps
      to preserve nutritional balance and lean mass/fat mass ratio and reduces age
      related insulin resistance. Moreover, physical activity has a beneficial
      influence on psychological function by improving cognitive performances and
      decreasing incidence of depression. Lastly, physical activity seems to reduce the
      incidence of several cancers, colic and mammary cancers particularly. PHYSICAL
      ACTIVITY, QUANTITY AND QUALITY OF LIFE: These multiple actions explain that
      physical activity, if it's adapted to subject's specificities increases
      longevity, delay entry in dependence and improves quality of life in older
      subjects. WHAT ARE THE RECOMMENDED ACTIVITIES: There is a superiority of
      individualized programs giving greater place to warm-up and associated endurance
      and resistive exercises intended to improve simultaneously cardiovascular and
      muscular functions. SPECIAL INTERESTS OF PHYSICAL ACTIVITY IN FRAIL AND VERY OLD
      SUBJECTS: Throughout its beneficial effects on aerobic capacity, muscular
      function, social integration, cognitive function and autonomy, physical activity
      may have a particular interest in frail subjects, when programs are adapted to
      physical capacities of these subjects and associated with nutritional
      supplements.

PMID- 10916539
TI  - [Prevention of falls and their consequences].
AB  - FREQUENCY AND SEVERITY: Approximately 30% of all elderly subjects experience a
      fall at least once a year. Hip fractures is the most severe consequence.
      PREVENTIVE MEASURES: The prevention of falls and hip fractures implies different
      strategies depending on the population concerned. For most all older subjects in
      good general health, one of the important risk factors is an abnormal single-leg
      stance which can reveal equilibrium disorders. For more frail subjects (20% of
      the elderly population), all factors must be considered, including, sarcopenia,
      nutritional status, and cognitive function. INSTITUTIONALIZED SUBJECTS: For
      institutionalized subjects, generally with multiple disease states, falls usually
      signal poor health, aggravated by multiple medications. One of the most frequent
      diseases observed in this population is Alzheimer type dementia. Adapted
      multidimensional management must be initiated within the framework of an overall
      gerontology policy to prevent falls and their consequences in institutionalized
      subjects.

PMID- 10916540
TI  - [Prevention of loss of functional independence and institutionalization].
AB  - LOSS OF FUNCTIONAL INDEPENDENCE: This is a serious problem in the management of
      older subjects. Prevention is necessary in order to assure better quality of life
      and avoid definitive institutionalization in a medical or social center. RELATED
      FACTORS: An analysis of the literature on the risk of loss of functional
      independence points out several medical (comorbidity, falls, cognitive capacity,
      sensorial deficiencies, nutrition, drugs), psychological (depression), and
      physical activity and social factors related to functional independence. RISK OF
      INSTITUTIONALIZATION: The risk is related to functional limitations and
      especially declining cognition, as well as social factors and the role of the
      primary care giver. PREVENTION: Systematic screening for risk factors is needed.
      The impact of measures to remedy certain medical risk factors has been clearly
      demonstrated. Specific programs can improve functional status, avoid
      institutionalization, and perhaps prolong survival.

PMID- 10916541
TI  - [Serious complication of an illegible prescription].

PMID- 10916542
TI  - [Role of the lipid formulation of amphotericin B in pediatric oncohematology].

PMID- 10916543
TI  - [Endoluminal vascular prostheses].
AB  - Endoluminal vascular prostheses that can be implanted by percutaneous routes
      represent the most recent development in vascular interventional radiology.
      Various commercially available types of prosthesis are presented and the
      construction principles and applications are described. At present secure
      indications for the implantation of endoluminal prostheses are limited to the
      elimination of aneurysms and arteriovenous fistulae of the large vessels near the
      trunk in sections that do not cross a joint. The wide use in peripheral occlusive
      diseases cannot yet be recommended because confirmed data are not available.

PMID- 10916544
TI  - [19F-MRT of pulmonary ventilation in the breath-hold technic using SF6 gas].
AB  - OBJECTIVE: Development of a method to analyze lung ventilation by 19F-magnetic
      resonance imaging (MRI) of inspired SF6 gas during breath hold. MATERIAL AND
      METHODS: Measurements were performed with a Siemens Magnetom Vision 1.5 T scanner
      using the conventional gradient overdrive. Coronal images of the lung were
      acquired using ultrafast gradient-echo pulse sequences with TR/TE/alpha = 1.4
      ms/0.48 ms/40 degrees without slice selection. With NEX = 200 averages and MA =
      32 x 64 raw data matrix, the acquisition time was 9 s/image. Higher spatial
      resolution of 4.7 x 6.3 x 15 mm3 was obtained with a three-dimensional pulse
      sequence (TR/TE/alpha = 1.6 ms/0.48 ms/65 degrees, NEX = 20) running for 49 s.
      Measurements wer performed in three anesthetized and ventilated pigs (18 kg).
      RESULTS: A nearly linear relation between SF6 concentration and 19F signal
      intensity was observed. The signal-to-noise ratio in images obtained without
      slice selection was 30.9, with slice selection it was 14.9. No differences
      between SF6 distribution to both lungs were observed in the animals. CONCLUSION:
      Breath-hold MRI of SF6 gas distribution in the lung was demonstrated for the
      first time. The low spin-density was compensated for by highly repetitive signal
      averaging. Breath-hold 19F-MR imaging of ventilated airspaces to assess SF6
      distribution in the human lung appears to be an interesting new method, which can
      be implemented with little technical efforts, and does not rely on radioactive
      isotopes.

PMID- 10916545
TI  - [The staging of bladder tumors in MRT: the value of the intravesical application
      of an iron oxide-containing contrast medium in combination with high-resolution
      T2-weighted imaging].
AB  - AIM: To investigate superparamagnetic iron oxide (SPIO) particles as
      intravesically applied contrast material in combination with high-resolution T2
      weighted MR imaging for the diagnostic assessment of urinary bladder tumors.
      METHODS: A prospective study was performed in 40 patients with suspected urinary
      bladder tumors who underwent MR imaging with a body phased-array coil at 1.5 T.
      Prior to imaging, a SPIO-containing solution (179.2 mg Fe/l) was instilled into
      the bladder. All patients were examined with T2-weighted, half-fourier acquired
      single shot turbo spin echo sequences and T1-weighted fast low angle shot
      sequences in 3 planes as well as a T2-weighted turbo spin echo sequence (TSE)
      using a 512 matrix. An additional gadolinium-enhanced dynamic study was performed
      in 33 patients. All patients underwent transurethral resection of the bladder or
      cystectomy. RESULTS: The combination of intravesically applied SPIO particles and
      a high-resolution T2-weighted TSE sequence depicted intravesical tumors as small
      as 4 mm. A reliable identification of the different layers of the bladder wall
      was possible in 5 cases only. The T2-weighted TSE sequence allowed the correct
      determination of the depth of infiltration in 29 of 36 patients with urothelial
      cancer by assessing the inner and outer boundary of the urinary bladder wall.
      This sequence had a diagnostic accuracy of 81% compared to 84% for the dynamic
      study (26/31). CONCLUSION: Even small tumors could be identified with the T2
      weighted TSE sequence after intravesical administration of SPIO particles but it
      was not possible to reliably differentiate the layers of the bladder wall. The
      results suggest that a dynamic MR imaging study cannot be dispensed with in
      patients with urinary bladder cancer.

PMID- 10916546
TI  - [The evaluation by CT of bone block position, interference screw placement and
      replacement of the anterior cruciate ligament after patellar ligament
      transplantation].
AB  - PURPOSE: Evaluation of arthroscopically assisted reconstruction of the anterior
      cruciate ligament using ligamentum patellae autografts in the bone-tendon-bone
      technique with special regard to the position of blocks and interference screws.
      MATERIAL AND METHODS: In a prospective study 28 patients were included after
      undergoing arthroscopic anterior cruciate ligament replacement surgery. Data thus
      obtained were correlated with the postoperatively determined functional
      parameters of the affected joint. RESULTS: Interference screws, bone-blocks and
      ligamentous transplants could be well imaged using CT. In a comparison of our
      data with clinical results there was a statistically highly significant
      correlation between clinical outcome and the position of bone-blocks and
      interference screws in the tibia. Angles between screw and bone-block exceeding a
      standard deviation led to significantly worse results, while a divergence in
      femoral angles did not lead to significantly worse results. CONCLUSION: The
      postoperative study of anterior cruciate ligament replacement surgery by CT
      enables the evaluation of the transplant as well as the position of bone-blocks
      and interference screws.

PMID- 10916547
TI  - [Magnetic resonance tomography of the brain in workers with chronic occupational
      manganese dioxide exposure].
AB  - AIM: Changes within the brain detected by MRI after chronic manganese poisoning
      raised the question whether morphological changes of the basal ganglia,
      particularly of the globus pallidus, could be detected after chronic occupational
      exposure to manganese dioxide. METHOD: In a cross-sectional study, healthy
      workers (48 male and 27 female) at a dry cell battery factory were examined.
      Actual internal exposure was quantified by the analysis of manganese in the blood
      using atomic absorption spectrometry. Chronic exposure was defined as a
      cumulative index (CBI) including duration of exposure, individual workplace
      factors, and previously measured concentrations of MnO2 in dust samples. A
      Philips Gyroscan T5-II (0.5 T) was used for the MRI of the brain. The following
      indicators were taken to ascertain possible manganese-induced changes; Pallidum
      Index (PI), width of 3rd ventricle and cella media index in addition to clinical
      examinations. RESULTS: No cases of parkinsonism were detected in clinical
      examinations or by other means. The mean manganese concentration in blood was 12
      micrograms/l (range: 3.9-23.3 micrograms/l). In comparison to the upper reference
      value of 10 micrograms/l, 42 workers (56%) had a higher body burden. A
      significant positive correlation between manganese levels in blood and the PI
      (indicated by T1-shortening) was observed as well as between the CBI and
      workplace-specific exposure. Brain atrophy was not detected in any of the
      observed cases. CONCLUSIONS: Long-term exposure to manganese dioxide dust
      correlates with the Pallidum-Index in MRI scans. Although the MRI findings have
      no current clinical relevance for individuals, further studies are necessary to
      evaluate specificity and potential prognostic value.

PMID- 10916549
TI  - [The MR signal behavior of a 4-week-old occlusive myocardial infarct in an animal
      experiment].
AB  - PURPOSE: To correlate signal behaviour in T1- and T2-weighted images after Gd
      DTPA with regional histopathology in occlusive myocardial infarction (MI).
      METHODS: Ligation of a diagonal branch of the LAD was performed in seven sheep.
      Four weeks later 0.1 mmol Gd-DTPA/kg were injected in five sheep 15 min before
      cardiac arrest and the sheep were slaughtered. In vitro imaging was performed at
      1.5 T included T1- and T2-weighted spin echo sequences in long and short axis
      views. Signal intensities (SI) were determined in 36 myocardial segments per
      slice and compared to macro- and microscopy. RESULTS: In all animals an antero
      lateral infarct region was evident histologically. This region presented with
      increased T2 SI and T1 SI after Gd-DTPA. The number of segments with increased SI
      in T1-weighted images was higher (n = 195 segments) compared to segments with
      increased T2 SI (n = 122 segments). Granulation tissue could be differentiated
      from rarely vascularized connective tissue at a high level of significance (p <
      0.001) by T1 and T2 SI analysis. Wall thickness was significantly decreased in
      necrotic myocardium (3.8 +/- 1.2 mm) compared to normal tissue (9.8 +/- 1.1 mm, p
      < 0.001). CONCLUSION: In four-week-old occlusive MI the extent of necrosis can be
      accurately assessed by analysis of post contrast T1-weighted images. Considering
      regional T2 SI, granulation tissue can be differentiated from regions with
      predominant fibrous organisation.

PMID- 10916548
TI  - [The T2-weighted half-Fourier acquired single-shot turbo-spin-echo technic
      compared to the conventional T2-weighted turbo-spin-echo technic for cerebral
      magnetic resonance tomography. A sequence comparison].
AB  - PURPOSE: To compare a T2-weighted half-fourier acquired single-shot turbo spin
      echo (HF-TSE) sequence (HA-STE-sequence) for cerebral MRI with a standard T2
      weighted fast spin-echo (TSE) sequence. MATERIALS AND METHODS: Signal-to-noise
      (SNR) and contrast-to-noise ratios (CNR) for different cerebral structures, and
      intracerebral lesions as well as the detectability of intracerebral lesions
      depending on size and relaxation properties were evaluated on cranial MR
      examinations of 46 patients with both a TSE and a HF-TSE sequence. RESULTS: SNR
      and CNR were found to be significantly higher with the TSE sequence for all
      normal structures and lesions except CSF, and lesions with short relaxation time
      T2 (p < 0.001). The number of detected lesions larger than 10 mm was similar with
      both sequences. Thirty-six (TSE) and 34 (HF-TSE) hyperintense, and 7 (TSE) and 2
      (HF-TSE) hypointense lesions of at least 5 mm but less than 10 mm in size were
      detected. Thirty-three (TSE) and 10 (HF-TSE) hyperintense, and 2 (TSE) and no (HF
      TSE) hypointense lesions smaller than 5 mm were detected. CONCLUSION: Due to its
      short acquisition time, the HF-TSE sequence is an alternative for MR examinations
      of non-compliant or claustrophobic patients. The low SNR and CNR relative to the
      TSE-technique are limiting factors as to the detectability of small lesions or
      lesions with low contrast to surrounding structures, with the risk of an
      increasing number of false negative results in lesions with short T2 relaxation
      time smaller than 10 mm.

PMID- 10916550
TI  - [A comparative study of analog and digital intraoral x-ray image detector
      systems].
AB  - The object of this investigation was to compare different intraoral, analog and
      digital X-ray image detector systems with respect to the diagnostic performance
      and to the relation of dose and image quality. METHODS: Three different intraoral
      film types and one digital system were compared. The same basic image quality
      related technical parameters were measured, Contrast detail diagrams and images
      of pig teeth were captured and evaluated by visual inspection. RESULTS: The
      digital system has a speed that is at twice as high as least of the most
      sensitive analog system. Compared to the analog system, the digital system
      visualizes better low contrast structures such as carious defects, but shows
      problems in visualisation of high dynamic ranges such as crown margins or
      fillings: insufficient suitable dynamic range. Larger objects such as incisors
      could not be imaged in one exposure due to the small area of the digital detector
      (24.3 x 18.2 mm). Retakes may be required due to the small dynamic range and
      detector area. CONCLUSIONS: The complete imaging of a tooth with crown and apical
      region, as required in the "radiological guidelines" is in doubt with digital
      systems having small active areas. The image quality of digital systems differs
      significantly from that of analog systems, nevertheless, the achievable image
      quality fulfills the requirements of intraoral dental radiology.

PMID- 10916551
TI  - [A combined PACS and Internet information system in a university medical center].
AB  - PURPOSE: The Department of Radiology at the University Hospital Innenstadt Munich
      provides all clinical departments of a large university hospital with several
      radiology units at different locations. During the last four years all units have
      been fully digitalized with a stepwise installation of a PACS. The PACS also
      processes images from the Nuclear Medicine Department. METHODS: As image
      modalities, archive systems and review workstations, we use devices from multiple
      vendors, which are integrated into a consistent system using the DICOM standard.
      The hospital has developed its own RIS and an Internet information system, which
      provides access to all reports and images from radiology for all clinical
      departments inside the hospital. Additionally, other clinical information such as
      laboratory results or ECG examinations are available through the system. RESULTS:
      After one year of operation, the system succeeded in the clinical routine work as
      the primary source for radiological reports and images as well as for laboratory
      values. CONCLUSION: The advantages of digitalization were, besides reduction of
      film cost, especially optimizations of work flow with access to digital images
      from everywhere at any time.

PMID- 10916552
TI  - [The radiation risks from x-ray studies for age assessment in criminal
      proceedings].
AB  - AIM: Age estimation for forensic purposes is, in general, based on a radiogram of
      the left hand or an orthopantomogram of the teeth. Two examples are given
      exemplifying the principal procedure that may be applied for estimating the
      radiation risks associated with the radiological examinations considered. METHOD:
      Mortality risks were calculated using the risk coefficients of ICRP and the mass
      ratio of radiation-exposed portion to total organ. For a radiogram of the hand, a
      radiation dose of 0.15 mGy was adopted. For an orthopantomogram the following
      doses were used: bone surface and red bone marrow 0.25 mGy, skin on the neck 0.56
      mGy, thyroid gland 0.053 mGy. RESULTS: Mortality risks obtained were 5.1 x 10(-8)
      for a radiogram of the hand and 1.8 x 10(-7) for an orthopantomogram. For
      comparison, it was estimated that the calculated risks might be equivalent to the
      mortality risks associated with public road traffic during less than one hour or
      about 2.5 hours, respectively. CONCLUSIONS: The calculated radiation risks are of
      a similar order of magnitude as are the risks the respective person is exposed to
      on the way to the medical examination or to the court. However, the applicability
      and the limits of the radiological procedures applied for age estimation require
      extensive and critical discussion.

PMID- 10916553
TI  - [Initial experiences with a new optical target system (SimpliCT) for CT-guided
      punctures].
AB  - PURPOSE: To evaluate the prototype of a new optical target device for CT-guided
      punctures and interventions. METHODS: An optical target device for CT-guided
      punctures was applied in 24 interventions. The system consists of a laser target
      device mounted on a stand. The biopsy needle is adjusted according the course of
      a laser beam. The target angle has to be adjusted on the laser unit. The laser
      carrier can be moved along an 90 degrees-angled rail, allowing punctures from any
      angle in plane. Furthermore, angulation in the z-plane is possible, supporting
      interventions with gantry tilt. Size and depth of the target lesions, the planned
      and the actual angle of the inserted needle, the numbers of corrections of the
      needle position, and the time required for the puncture were evaluated. The user
      rated the benefit of the system and the ease of the application. RESULTS: All 24
      interventions were carried out successfully. The mean difference between the
      planned and the actual angle of the needle was 1.3 degrees (SD: 0.7 degree). The
      system was considered as easy to handle and as a valuable aid. CONCLUSIONS: The
      laser target device is a simple navigation system which allows accurate
      positioning of a needle. Requiring an acceptable low preparation time, it easily
      can be integrated into the procedure.

PMID- 10916554
TI  - [Pneumopericardium and masked aortic rupture in thoracic contusion].

PMID- 10916555
TI  - [Fasciola hepatica: the sonographic and computed tomographic changes in a case
      with a liver fluke].

PMID- 10916556
TI  - The position of the monozygotic twins among their school class-mates in the light
      of results of Janusz Korczak's "Plebiscite on likes and dislikes".
AB  - Within the "Wroclaw Longitudinal Twin Study" in a part of the material the liking
      level of singletons (SIN) to identical twins (TMZ) and of TMZ to SIN was analysed
      cross-sectionally, in the period of 11th to 18th year of life. In each of the 76
      classes of elementary and high schools in Wroclaw (Poland), including the
      investigated in 1976-7 TMZ (64 pairs), were evaluated the relations between
      school-mates, using the Korczak's five-degree scale of liking. The declared by
      TMZ and SIN liking decreased with age between pupils of the same sex, and
      increased between pupils of opposite sex, however, in TMZ with some delay. The
      liking declared by TMZ of both sexes to SIN was on average lower than that
      declared by SIN to TMZ. The degree of liking declared by SIN to TMZ of the same
      sex was average higher than in relation of SIN to SIN particularly among girls.
      Thus, there occurred the so-called "prima donna effect". The liking declared to
      pupils of opposite sex in relation of SIN to TMZ was on average lower than the
      analogous one in relation of SIN to SIN and in relation TMZ to SIN even worse.
      The higher contrast in treating pupils of the same and opposite sex in TMZ than
      in SIN indicates a lower social maturity in TMZ. A diverse influence of socio
      economic conditions on the declared toward then liking by boys and girls was
      found. The low number of separated twins did not allow to make a generalisation
      on specificity of their position in class. The sending of TMZ to different
      classes appeared to be in Wroclaw elementary schools sporadic (1 repeater), and
      in high schools observed in 38%, from that 28% of twins went to equivalent
      classes, usually in different school, and in 10% of pairs one of the twins
      repeated the class.

PMID- 10916557
TI  - Interpersonal conflicts in the relationship of twins.
AB  - Taking into consideration two facts: that the structure of social life forces
      twins to part and that the presented roles in a pair are not equal, (one of the
      twins plays the role of a leader (L) and the other, the subordinate (P.)), one
      can ask the question--what meaning does the moment of parting have and what are
      its consequences? In order to do that, a survey was conducted, (a sample of 31
      pairs of twins above the age of 30), in which every pair was asked the question:
      "Which one of you made the decision about parting?" The answer had two options: A
      -I, B--brother/sister. Out of 31 pairs of twins, 16 pairs chose the variant
      different from his brother or sister--that is A, B, admitting that the
      interpersonal conflict was the result of the parting. In 7 pairs, both twins
      chose the B variant--they withdrew from the conflict; and in 8 pairs they chose
      the A variant--looking for a compromise as the means of agreement. When analyzing
      the results of the survey, we can state the following: in the relationship of
      twins, there is an interpersonal conflict; the decision about parting is
      difficult with prevalent feelings of sadness and sorrow; after parting, at least
      one of the twins has problems with preserving his identity and integrity of
      psychological space. Since the moment of parting is necessary and difficult,
      specialists and mainly parents are required to consciously change their position
      towards the relationship of twins. It has to be the result of applied educational
      methods which aim at creating subjectivity and equality of each of the twins
      before the moment of parting.

PMID- 10916558
TI  - Renal blood flow in twins.
AB  - The aim of this preliminary study was the estimation of renal blood flow in 16
      premature newborns from twin pregnancies with mean body weight 1270 g and mean
      gestational age 29 weeks. In control group we have 16 singleton newborns with
      mean gestational age 29 weeks and mean birth weight 1240 g. In both intervention
      and control group we have the similar clinical symptoms. The renal blood flow was
      carried out in the first day of life with the Acuson 128 XP Colour Doppler using
      the 6 and 7 MHz linear transducer. The renal blood flow parameters-PI, RI, Vmax,
      Vmin Vmean were measured in right and left renal arteries in theirs courses from
      the aorta to the renal hilus, by color sinal. In the investigation group the mean
      value of RI in right and left renal artery was 0.88. Mean PI in right vessel was
      1.67 and in left 1.56. Mean V min in right and in left artery was 0.03 and mean V
      max in right artery was 0.34 and in left 0.33. Mean value of mean velocity in
      right vessels was 0.18 and in left 0.19. In control group we observed in right
      artery mean value of PI 1.74 and in left 1.6. Mean RI was 0.86 and 0.86 in right
      vessel in left vessel. Mean V min was 0.05 in right and 0.04 in left artery. Mean
      V max was 0.37 in right and 0.34 in left artery. Mean value of V mean was 0.19 in
      right artery and 0.18 in left artery. Using the student, Mann-Whitney and Shapiro
      Wilk tests we have not observed statistically significant difference of Doppler
      parameters between control and investigation group and between the left and right
      artery. Although in newborns with broad PDA we noted significant higher value of
      RI (0.97, 0.98) than in newborns without PDA (0.78, 0.81).

PMID- 10916560
TI  - Yolk sacs in twin pregnancy.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between the
      yolk sacs separated or not separated by septum and chorionicity twin pregnancies
      scanned early in the first trimester, and the relation between size and
      morphologic features of the yolk sac and the outcome of twin pregnancies.
      RESULTS: In all 38 sets of twins two yolk sacs were identified. During the first
      trimester of a dichorionic twin pregnancy, the yolk sacs were always separated by
      a septum and not separated ("Eight" sign) in monochorionic twin pregnancy. In
      five cases, one of yolk sac was abnormally large (> 8 mm) and had thin wall. Four
      of the five mothers spontaneously aborted during the next 2-3 weeks. In one case
      of monochorionic twin ectopic pregnancy two yolk sacs were seen normally.
      CONCLUSION: The sonographic identification of yolk sacs in multiple pregnancies
      allows an early and efficient recognition of presence and chorionicity of twin
      pregnancy, both in intra- and extrauterine. Identification of abnormal yolk sac
      or yolk sacs suggests death of one or all embryos.

PMID- 10916559
TI  - Type 1 diabetes and prediabetic state in a monozygotic triplet.
AB  - Type 1 diabetes mellitus (IDDM) results from a chronic process of autoimmune
      destruction of beta cells of the Langerhans islets. The presence of
      autoantibodies (ICA, GADA, anti-IA2, IAA) in serum precedes the clinical onset of
      the disease. Genetic predisposition for IDDM is connected with HLA, CTLA-4 and
      insulin gene region. The aim of the study was the genetic and immunological
      analysis of a triplet. One of them developed Type 1 diabetes mellitus. We
      analysed HLA class II, CTLA-4 and insulin gene polymorphisms in the whole family.
      Besides, we investigated immunological status of three brothers. All patients
      present identical genotype for VNTR loci: D1S80, D17S5 and Apo B, as well as for
      HLA-DRB1, -DQA1, -DQB1, CTLA-4 gene and all studied insulin gene polymorphisms.
      That proves their monozigosity. The triplet presents strong genetic
      predisposition for IDDM. The two patients without overt diabetes have increased
      levels of ICA, GADA, IA2 and IAA.

PMID- 10916561
TI  - The uterine capacity measured by the total twin birth weight and duration of twin
      pregnancy.
AB  - The objective of this study was to answer the question whether there is the
      relation between the uterine capacity, estimated by the total birth weight of
      fetuses, and the duration of twin gestation. The material for researches contains
      data received from the books of births and case records concerning the pregnant
      who gave births to twins in the Institute of Obstetrics and Gynecology of the
      Medical University in Lodz between 1970-1998. The final analysis concerned only
      gestations lasting more than 29 weeks, without any complications (excluding
      prematurity and the growth-discordant twins), and when gestational age was
      exactly known. The selected group was finally composed of 188 pairs of twins. The
      analyses considered relations between total birth weight of twins, the sex of
      newborn babies, parity, and the duration of gestation. The duration of the
      analyzed twin pregnancies was 35.6 weeks, including primiparous with 35.8 weeks,
      and multiparous--35.1 weeks. In the group of male-male twin pairs the average
      duration of pregnancy was 35.7 weeks, in unlike-sexed pairs--35.6 weeks, and in
      female-female pairs--35.5. In the group of the primiparous having male-male twin
      pairs the average duration of pregnancy was 35.1 weeks, unlike-sexed pairs--36.4
      weeks and female female pairs--36.6 weeks, while in the group of multiparous
      relatively: 36.4, 35.4, 35.0 weeks. The total birth weight of the specific pairs
      of twins was from 2270 g to 6900 g (average 4794 g), while in 92% < 5500 g. In
      the primiparous group it was 4908.1 g. and in the multiparous group--4663.1 g.
      Analyzing the total twins' weight according to the fetal gender and parity it was
      found that in primiparous with male-male twins--4715.3, unlike-sexed--5271.6 and
      female-female--4967.5, whereas in multiparous relatively: 4961.5, 4692.6, 4414.0.
      The shortening of twin pregnancies was caused by the following factors: total
      body mass achieved by fetuses was > 5500 g, presence of male sex in twin
      pregnancies (only in primiparous), and also the multiparity.

PMID- 10916562
TI  - Multiple pregnancy: factors contributing to early infant's breast-feeding--own
      experience.
AB  - The aims of the study were as follows: 1. to evaluate the effectiveness of
      current program to promote breast-feeding in our population of infants from
      multiple pregnancy; 2. to define factors responsible for failure in early breast
      feeding establishing and/or maintaining breast-feed during the hospitalization of
      the babies in neonatal department. 122 newborn infants (2 sets of triplets and 58
      twin pairs) born in the Clinic for Pathology of Pregnancy and Labor in Szczecin,
      Poland, in the years 1995 (January)-1999 (May) from multiple pregnancy were
      included in the study. In the examined material there were estimated neonatal
      conditions at birth, neonatal complications, which may disturb successful breast
      feeding as well as other factors contributing to early breast-feeding, the way of
      feeding the babies during neonatal period and the mean time of starting breast
      feeding. It was found that most of the examined babies were born with the
      features of prematurity: mean gestational age was 35.6 +/- 2.2 weeks and mean
      birthweight--2225.3 +/- 193.2 grams. Only 57.4% of babies were born in good
      conditions according to Apgar scores. Factors which influence in a negative way
      early breast-feeding were as follows: respiratory disturbance (22.1%), temporary
      oral nutrition intolerance due to sickness of the baby or early onset of
      infections (27.5%), operative delivery (62.3%), medicine taken by mothers (13.9%)
      and failure in maternal lactation (8.2%). Factors disturbing a normal course of
      breast-feeding were: phototherapy due to hyperbilirubinemia (20.5%) and late
      onset of infections (1.6%). In most cases breast-feeding was started 3-4 days
      after birth and the most frequent way of feeding was formula followed or in
      combination with maternal milk (at discharge in 86.9% of babies). We concluded
      that exclusive breast-feeding, despite program of promotion, is a rarity in
      population of newborn babies born from multiple pregnancy; time to start breast
      feeding in this population is usually 3-4 days after delivery. Most pre-term and
      full-term twins are discharged from neonatal department on maternal milk-
      exclusively or in combination with formula in situation of scarce maternal milk
      for two or more infants--what should be considered as our professional success.

PMID- 10916563
TI  - Fetal and neonatal arrhythmia in one of the twins--a case history.
AB  - There are a lot of publications about fetal arrhythmia in singletons, but up to
      now there are no published data about fetal arrhythmia in multiple pregnancies.
      In the present study a case history of fetal and neonatal arrhythmia in one of
      twins from two mothers treated with betamimetic agents due to imminent preterm
      labor is reported and discussed. A first case with fetal bradycardia due to
      complete A-V block had congenital cordis abnormalities (VSD and PFO). The second
      case with prenatal detected extrasystoles had normal heart anatomy. Digoxin was
      administered to the mother, in the aim to treat fetal arrhythmia without success,
      because the baby had postnatal bradycardia. After hospitalisation in Cardiology
      Department the described cases were successfully treated. In both cases the
      second twins were without neonatal arrhythmia and with no structural heart
      abnormalities. We summarise that in situation of detection fetal arrhythmia the
      complexity of the problems experienced may warrant early referral to a tertiary
      centre where the overall management of the mother, fetus and neonate, may be
      undertaken.

PMID- 10916564
TI  - A case of successful twin pregnancy placed in separate horns of bicornuate,
      unicollis uterus.
AB  - We described a case of pregnancy, delivery and peurperium of 28 years old
      multipara with twins pregnancy in bicornuate, unicollis uterus. Each fetus was
      placed in separate horn of uterus. Biological mature pregnancy was delivered by
      cesarean section. During the peurperium the involution disturbances of one of the
      uterus horns were observed. The case was discussed in context of other similar
      anomalies.

PMID- 10916565
TI  - Neurodevelopmental dysfunction and specific learning disabilities in school-aged
      twins.
AB  - The frequency of the developmental dysfunction and specific learning disabilities
      were assessed in the retrospective study in the group of 56 school-aged twins.
      The relationships between genetic, perinatal and social factors and learning
      disability were also determined. It was found that 12.5% of twins had learning
      disabilities. The most common neurodevelopmental dysfunction were language
      disorders, poor graphomotor fluency and poor fine motor dexterity. It was also
      found that educational difficulty were associated with prematurity, low Apgar
      scores, neonatal complications and familial predisposition.

PMID- 10916566
TI  - From the research on electrophoretical mobility of nuclei in twins.
AB  - I studied 8 pairs of male twins and 14 pairs of female twins. The aim of this
      paper is to demonstrate the evaluation of development age in pairs of twins
      examined through the electrophoretical mobility of nuclei. EMN index in pairs of
      male twins, the index figures do not change dramatically between the ages of 8
      12. EMN index in pairs of female twins rises from 9-year-old to 11-year-old pair.
      In this paper I want to indicate the studies on development age, which began at
      The Twins Festival in Szczecin in 1998.

PMID- 10916567
TI  - Characteristics of adaptation period for extrauterine life of neonates from
      multiple pregnancies.

PMID- 10916569
TI  - Long-term follow-up study of somatic development in prematurely born twins after
      life-threatening episodes.
AB  - The study comprised 14 pairs of twins. All the children were prematurely born
      between the 27 and the 33 weeks of pregnancy with birth weight 600-1900 g.
      Somatic development was assessed on the basis of the body weight, length/height
      measurements taken in the 6th and 12th months of the corrected age and in the
      24th month of the calendar age. Body mass index was also calculated as weight in
      kilograms divided by the square of the height in meters. The obtained results
      were compared with the regional norms for children from Lodz. Moreover, in each
      child individual measurements and body mass index were normalized as compared to
      the arithmetic mean and the standard deviation for the established age norm. The
      percentage of children with body mass deficiency and decreased body length/height
      was relatively high. Individual assessment of somatic development, taking into
      account the normalized values enable observation of the direction of changes
      within the range of somatic features in individual children. Retardation of
      somatic development of prematurely born twins should be first of all associated
      with their very low birth weight. Severe complications of prematurity affect
      physical development of the children examined by us, especially in the first two
      years of life.

PMID- 10916568
TI  - Ultrasound in the diagnosis of twin-to-twin transfusion syndrome--a preliminary
      report.
AB  - OBJECTIVE: The aim of this study was to show the diagnostic possibilities of
      ultrasound in twin-to-twin transfusion syndrome (TTTS), to demonstrate its
      usefulness in cases of hemoglobin difference < 5 g/dL in neonates as well as in
      cases complicated by intrauterine death of one or both twins. STUDY DESIGN: The
      study included 4 pairs of twins. In two cases 3 fetuses died in utero. In the
      other two the hemoglobin difference in newborn infants was < 5 g/dL. The
      ultrasound examination, evaluating the fetal anatomy and biometry, amniotic fluid
      volume, placentation, was performed. The special attention was paid to
      polyhydramnios/oligohydramnios, discordant fetal growth (fetal weight, abdominal
      circumference), the presence of fetal hydrops, ascites, pericardial effusion.
      Doppler blood flow velocimetry has been done in umbilical vessels, middle
      cerebral artery. The data was compared with normal reference values for singleton
      pregnancies. The waveforms from both uterine arteries were also evaluated to
      exclude placental insufficiency. Additionally the blood flow through the AV
      valves was measured to exclude or confirm its regurgitation. Postnatally the
      hemoglobin difference was evaluated if available and compared with sonographic
      findings. RESULTS: In all cases inter-twin difference in abdominal circumference
      was greater than 18 mm and inter-twin weight difference of more than 15%. We
      observed polyhydramnios/oligohydramnios in all twin pregnancies. It has been
      found decreased PI in middle cerebral artery in larger fetus (recipient) in all
      our cases (comparing to single pregnancy). PI values for this vessel in smaller
      fetuses were within normal range (for single pregnancy). PI values in umbilical
      arteries of recipients were abnormal (increased PI or absent end-diastolic flow).
      COMMENTS: The sonographic criteria seem to be very useful in diagnosis of twin-to
      twin transfusion syndrome, especially in cases where the measurement of
      hemoglobin level is impossible. Doppler blood flow velocimetry in fetal vessels
      helps to explain the changes in fetal hemodynamics in TTTS.

PMID- 10916570
TI  - Analysis of triple test results in 27 cases of twin pregnancies.
AB  - The study comprises 889 pregnant women between 14 and 21 weeks of gestation. The
      control group consisted of 862 pregnant women with unburdened obstetric anamnesis
      with an uneventful singleton pregnancy. The examined group consisted of 27
      pregnant women with uncomplicated twin pregnancy. In the sera of pregnant women
      AFP (Microparticle Enzyme Immunoassay AxSYM Abbott), total beta-hCG
      (Microparticle Enzyme Immunoassay AxSYM Abbott) and unconjugated estriol
      (Radioimmunoassay Amerlex-M. 2T Johnson & Johnson Ortho Clinical Diagnostics
      Ltd.) were determined. The risk of fetal trisomy 21 was calculated with the use
      of PRISCA 3.0 software, which corrected the MoM values for twin pregnancy. Ulm
      Index was also calculated. In the majority of twin pregnancies increased
      concentrations of AFP, total beta-hCG and uE3 in the range over 1.0 MoM was
      noted. In the group of women below 35 years of age with singleton pregnancies
      using PRISCA 3.0 software it approximated to 95%. For women older than 35 optimum
      index for fetal trisomy 21 risk calculation was Ulm Index with the specificity
      93.8%. The specificity of AFP determination in the detection of fetal open NTD in
      singleton pregnancy was 99%. In the group of women with twin pregnancy the
      obtained specificity of 77.8% for PRISCA 3.0 software is low, a more advantageous
      way to calculate the risk of fetal trisomy 21 is Ulm Index with the specificity
      of 85.2%. The specificity of AFP determination as a screening for fetal open NTD
      in twin pregnancy was 96.3%.

PMID- 10916571
TI  - Prevalence and forms of congenital anomalies in twins born in Pomeranian District
      during the period from 1.07.1997 to 31.12.1998. Polish Register of Congenital
      Anomalies.
AB  - The authors have analysed the frequency and structure of congenital anomalies in
      children born in the Pomeranian district in the period from 01.07.1997 to
      31.12.1998. Among a total of 28.361 births in that area, 748 (2.64%) were
      affected by congenital anomalies. Among 28.361 births, 620 (2.18%) were from
      multiple pregnancies. 23 (3.71%) among births from multiple pregnancies were
      affected by congenital malformations. The prevalence rate of inborn anomalies in
      births from multiple pregnancy in our area were higher (3.71%) in comparison to
      births from singleton pregnancy (2.61%). It implies that children born from
      multiple pregnancy are at higher risk of developing congenital anomalies.

PMID- 10916572
TI  - The emotional basis of linguistic and nonlinguistic intonation: implications for
      hemispheric specialization.
AB  - Clinical and experimental studies suggest that the right cerebral hemisphere is
      dominant for intonation or the "melody of language." In light of this brain
      behavior correlation, an assessment of intonation is a useful adjunct of the
      linguistic, cognitive, and neurological evaluation of patients with brain damage.
      However, the neural basis of intonation is controversial. This article examines 1
      of the unresolved issues--the hypothesis that emotional versus linguistic
      categories of intonation are lateralized to the opposite hemispheres. A review of
      linguistic and neurobehavioral evidence fails to support the claim that
      intonation is divided into dichotomous categories. Linguistic analysis suggests
      that even intonation patterns traditionally described as nonemotional have their
      underpinnings in the speaker's emotions. Similarly, studies of adults and
      children with brain damage indicate that intonation patterns described as either
      linguistic or emotional are mediated by right-hemisphere substrate specialized
      for emotional experience. The cross-disciplinary findings support a general right
      hemisphere hypothesis that unifies linguistic and emotional uses of intonation in
      children and adults. Implications of the hypothesis are discussed in relation to
      the diagnosis of developmental disorders, with special attention to the problem
      of identifying language impairment in infants and toddlers.

PMID- 10916573
TI  - How children with neurofibromatosis type 1 differ from "typical" learning
      disabled clinic attenders: nonverbal learning disabilities revisited.
AB  - To further investigate cognitive deficits in children with Neurofibromatosis Type
      1 (NF-1), children with NF-1 were compared to typical learning disabled clinic
      attenders (LD-clinic), all of whom had reading disabilities, as well as to a
      group with no disabilities (NoDx). Results indicated that both the NF-1 group and
      LD-clinic group had reading and reading-related deficits when compared to the
      NoDx group; however, the NF-1 group was more globally language impaired than the
      LD-clinic group. In addition, the NF-1 group scored significantly lower than the
      LD-clinic group, but not the NoDx group, on the visuospatial measures, thus
      confirming that children with NF-1 have visuospatial deficits not typical of a
      general LD-clinic population. The NF-1 group was not impaired in comparison to
      the NoDx group on certain language and visuospatial tasks that were previously
      found to be deficits in sibling pairwise matched designs; thus, the importance of
      considering genetic and familial context when studying the impact of genetic
      disorders on cognition was demonstrated.

PMID- 10916574
TI  - A lesion analysis of visual orienting performance in children with cerebral
      vascular injury.
AB  - Anterior brain insults during development have been shown to result in visual
      orienting deficits; however, the type of orienting deficit has varied across
      studies. Performance on an orienting task was examined in relation to the
      location and volume of injury on magnetic resonance exams in 15 children with
      cerebral infarction and 32 control children. Contralateral lesions including the
      parietal lobe were associated with larger validity effects, suggesting
      difficulties disengaging attention. A similar trend was found for the middle
      frontal gyrus. Basal ganglia injury contralateral to a given hemifield was
      associated with less facilitation of attention. Lesion volume in each hemisphere
      did not show a significant relation with contralateral validity effects. The data
      suggest that variability in the type of visual orienting deficits shown in prior
      studies of children with anterior brain insults may be related in part to the
      specific location of lesions within the frontal lobe.

PMID- 10916575
TI  - Judgment of duration in individuals with ataxia-telangiectasia.
AB  - Several clinical investigations with adults suggest that the cerebellum may be
      critical for judgment of explicit time intervals; however, little work has been
      done in populations with lesions of the cerebellum acquired during development.
      We evaluated 17 individuals with ataxia-telangiectasia (AT), an autosomal
      recessive disorder with on-set in early childhood characterized by diffuse,
      almost selective, degeneration of the cerebellar cortex, and 21 normal controls,
      matched for age. Because patients with AT have motor impairment, verbal IQ (VIQ)
      was used to estimate intelligence; VIQ was significantly lower in the group with
      AT (p < .0001). Participants were tested using a test of judgment of duration
      that has been found to be impaired in adults with cerebellar lesions and a
      contrasting auditory control task (not impaired in adults with cerebellar
      lesions) involving judgment of pitch. After statistically controlling for VIQ,
      the 2 groups did not differ significantly on judgment of pitch, but those with AT
      performed significantly worse than controls on judgment of duration (p = .01).
      Children and adolescents with AT show deficits in judgment of duration but not of
      pitch, suggesting that the cerebellum may be critical for judgment of explicit
      time intervals at all ages.

PMID- 10916576
TI  - A hierarchical analysis of block design errors in children with early focal brain
      damage.
AB  - This study investigated the differential effects of very early damage to the left
      hemisphere (LH) or right hemisphere (RH) on visuospatial processing. Twenty-two
      children who had suffered either LH or RH strokes in the pre- or perinatal period
      were included in the study. The Block Design subtest of the Wechsler Intelligence
      Scale for Children-Revised (Wechsler, 1974) was used. Each missed item was coded
      as either a global error (e.g., broken configuration), local error (e.g.,
      incorrect details), or time fail error (i.e., not completed within the allotted
      time). Results showed that the LH lesion and RH lesion groups had similar full
      scale IQs, verbal IQs, and performance IQs and were within the average to low
      average range. Block Design scaled scores were also within the average to low
      average range and did not significantly differ between the 2 lesion groups. Error
      analysis revealed, however, that the RH focal lesion group produced a
      significantly higher percentage of global errors than did the LH lesion group,
      whereas the LH lesion group produced a significantly higher percentage of local
      errors than did the RH lesion group. The groups did not differ on their
      percentage of time fail errors. These results are consistent with previous
      findings that suggest that the RH is involved in more global aspects of visual
      processing, whereas the LH mediates the more detailed, local aspects of visual
      information. The fact that these differences in processing are present after such
      early focal damage implies that hemispheric specialization for visuospatial
      processing occurs very early in brain development.

PMID- 10916578
TI  - Expressive vocabulary ability of toddlers with Williams syndrome or Down
      syndrome: a comparison.
AB  - School-aged children and adults with Williams syndrome have repeatedly been found
      to evidence an expressive vocabulary advantage relative to same-aged individuals
      with Down syndrome. However, Singer Harris, Bellugi, Bates, Jones, and Rossen
      (1997) argued that this advantage is reversed during the initial period of
      language acquisition; during this time, children with Down syndrome have larger
      expressive vocabularies than children with Williams syndrome. This result may
      have been due to methodological problems, however. This study uses a different
      design to reconsider the question of whether toddlers with Williams syndrome show
      an expressive vocabulary advantage over same-aged toddlers with Down syndrome.
      Parents of twenty-four 2-year-olds with Williams syndrome and twenty-eight 2-year
      olds with Down syndrome completed the vocabulary checklist from the MacArthur
      Communicative Development Inventory: Words and Sentences. The 2 groups were
      carefully matched for chronological age (CA). Results indicated that the toddlers
      with Williams syndrome had substantially and significantly larger expressive
      vocabulary sizes than did the CA-matched children with Down syndrome. Additional
      analyses of children for whom data were available between the ages of 2 years 0
      months and 2 years 3 months indicated that the expressive vocabulary advantage
      for children with Williams syndrome was present even at this very young age when
      none of the children had begun to produce word combinations. The Discussion
      section that follows addresses the discrepancy between these findings and those
      of Singer Harris et al. and considers the variability present within both the
      Williams syndrome and Down syndrome samples. Also discussed is the continuity
      across the lifespan in both the expressive vocabulary advantage shown by
      individuals with Williams syndrome relative to same-aged individuals with Down
      syndrome and the expressive vocabulary variability within each syndrome.

PMID- 10916577
TI  - Language-based cognitive functioning in parents of offspring with ADHD comorbid
      for Tourette syndrome or learning disabilities.
AB  - The parents of children diagnosed with attention deficit hyperactivity disorder
      (ADHD) were examined for characteristics symptomatic of 2 comorbidities (Co)
      within their offspring with ADHD: Tourette syndrome (TS) and language-based
      learning disabilities (LD). A 2 x 2 multivariate analysis of variance design was
      used; the parents were divided according to whether the offspring with ADHD had
      TS (Co-TS) or not (No Co-TS) and whether offspring had LD (Co-LD) or not (No Co
      LD). Parents (86 mothers and 70 fathers) were administered the short form of the
      Wechsler Adult Intelligence Scale--Revised (WAIS-R; Wechsler, 1981), subtests of
      the Woodcock-Johnson Cognitive and Achievement Batteries (Woodcock & Johnson,
      1989), and word fluency (semantic and letter; Benton & Hamsher, 1989; Wiig &
      Semel, 1987). The fathers of offspring with Co-TS were more likely to be
      diagnosed with LD and had lower WAIS-R Vocabulary, Arithmetic, and Picture
      Arrangement scores. In addition, when the WAIS-R full scale IQ was used as a
      covariate, these fathers had lower Woodcock-Johnson Oral Vocabulary, Spelling,
      and Reading scores (as measured by Letter-Word Identification). The mothers of
      children with Co-TS had lower WAIS-R Vocabulary scores. Parents of the children
      with No Co-TS showed a higher proportion of error patterns on the word fluency
      tasks involving repetitions and rule breaks. The findings show that it was the
      parents of the children with Co-TS, not the parents of the children with Co-LD,
      who showed language-based learning problems. In separate discriminant analyses
      for the fathers and mothers, when the aforementioned significant parental
      measures were used as predictors, 81% of offspring with Co-TS were correctly
      classified as having a diagnosis of TS, solely on the basis of characteristics in
      their parents.

PMID- 10916579
TI  - Towards a science of the management of health care.

PMID- 10916580
TI  - Physician benchmarking: measuring variation in practice behavior in treatment of
      otitis media.
AB  - The study uses Data Envelopment Analysis (DEA) to analyze physician practice
      behavior and develops measures of physician practice efficiency as a basis for
      improving productivity and reducing costs in otitis media treatment. Other
      objectives include determining geographic variations in practice patterns for
      otitis media, and the impact of inefficient practice patterns on the cost of
      treatment of otitis media. Only 46 (28.8%) of the 160 physicians were classified
      as efficient. Average total cost of an episode by efficient providers was $357.03
      and $492.06 for inefficient providers. By restricting particular inputs and
      outputs, and directing all physicians to treat otitis media through a balanced
      primary care model, physicians would be able to provide the same quality care at
      an average savings of 23.7% per efficient and 4.4% per inefficient provider.

PMID- 10916582
TI  - An investigation of neural networks in thyroid function diagnosis.
AB  - We investigate the potential of artificial neural networks in diagnosing thyroid
      diseases. The robustness of neural networks with regard to sampling variations is
      examined using a cross-validation method. We illustrate the link between neural
      networks and traditional Bayesian classifiers. Neural networks can provide good
      estimates of posterior probabilities and hence can have better classification
      performance than traditional statistical methods such as logistic regression. The
      neural network models are further shown to be robust to sampling variations. It
      is demonstrated that for medical diagnosis problems where the data are often
      highly unbalanced, neural networks can be a promising classification method for
      practical use.

PMID- 10916581
TI  - Multifactor efficiency in data envelopment analysis with an application to urban
      hospitals.
AB  - A perennial difficulty in measuring hospital efficiency, and one with important
      policy implications, is how to compare teaching versus non-teaching hospitals.
      This problem reflects a broader methodological concern in Data Envelopment
      Analysis (DEA), which is the comparison of specialist and non-specialist Decision
      Making Units (DMUs). This paper presents a new performance measure in DEA, termed
      multifactor efficiency, which represents an average partial factor productivity
      index summed over all output-input ratios. We apply this technique to measure the
      performance of 27 large, urban hospitals, including 13 teaching hospitals. These
      results were reviewed and validated by a panel of health care experts, and
      multifactor efficiency was shown to offer several benefits that enhance and
      complement existing performance measures in DEA.

PMID- 10916583
TI  - Why do patients prefer hospital emergency visits? A nested multinomial logit
      analysis for patient-initiated contacts.
AB  - This paper analyzes the nature of health care provider choice in the case of
      patient-initiated contacts, with special reference to a National Health Service
      setting, where monetary prices are zero and general practitioners act as
      gatekeepers to publicly financed specialized care. We focus our attention on the
      factors that may explain the continuously increasing use of hospital emergency
      visits as opposed to other provider alternatives. An extended version of a
      discrete choice model of demand for patient-initiated contacts is presented,
      allowing for individual and town residence size differences in perceived quality
      (preferences) between alternative providers and including travel and waiting time
      as non-monetary costs. Results of a nested multinomial logit model of provider
      choice are presented. Individual choice between alternatives considers, in a
      repeated nested structure, self-care, primary care, hospital and clinic emergency
      services. Welfare implications and income effects are analyzed by computing
      compensating variations, and by simulating the effects of user fees by levels of
      income. Results indicate that compensating variation per visit is higher than the
      direct marginal cost of emergency visits, and consequently, emergency visits do
      not appear as an inefficient alternative even for non-urgent conditions.

PMID- 10916584
TI  - Use of statistical process control for surveillance of pulmonary dysfunction in
      groups in the workplace.
AB  - Workplace surveillance is an essential feature of an effective occupational
      health program. Unfortunately, many health care organizations are beginning to
      collect large quantities of clinical information without much thought to
      subsequent application. In this paper, we propose a screening technique to help
      manage this situation. Specifically, we advocate "control charts for fraction non
      conforming" for use in the medical surveillance of work areas. A military
      installation in the mid-western United States with 63 work areas is analyzed
      using up to seven years worth of spirometry data. Based on the results of 6
      separate tests, a classification of normal or abnormal was made for each
      individual and the percent of abnormalities by area and year was calculated. The
      results were analyzed via control charts and contrasted to a preset percentage
      method. Cigarette smoking was then controlled for in the analysis to account for
      abnormalities that may be occupationally related versus personal habits. We
      demonstrate the utility of control charts for the compact display of surveillance
      data and show how it can aid in the analysis of an extremely complex health care
      concern. A recommendation is made for managing a surveillance program using
      spirometry and control charts and supported by follow-on investigation of two
      areas flagged as abnormal by the procedure.

PMID- 10916586
TI  - Health care management modelling: a process perspective.
AB  - Modelling-based health care management ought to become just as popular as
      evidence based medicine. Making managerial decisions based on evidence by
      modelling efforts is certainly a step forward. Examples can be given of many
      successful applications in different areas of decision making: disease process
      modelling, screening and prevention policy development, resource allocation,
      waiting lists and waiting times, patient scheduling. Also examples can be given
      which would have benefited by prior modelling, for example adverse effects of
      health care system reform decisions. This contribution aims at giving an overview
      of health care management modelling areas, and observations from a European
      perspective on developing successful health care management models. The overview
      is created by presenting different reference frameworks for mapping health care
      management modelling applications. We report a development from an almost
      arbitrary list of applications used for bibliographic purposes (scheduling,
      simulation, queueing, etc.) towards frameworks that focus on the process of
      delivery. The advantage of mapping modelling applications in this way is that we
      are able to position contributions within a reference framework with a focus on
      processes, with the patient process at the top. The acceptance of process
      orientation as a basis for modelling has consequences for the way models are
      developed. Close cooperation between modeller and manager and a profound insight
      into the dynamics of the modelling area concerned are important requirements for
      developing successful models. This is illustrated for waiting lists as an area of
      modelling.

PMID- 10916585
TI  - Computers in the consulting room: a case study of clinician and patient
      perspectives.
AB  - Few clinicians in the United States use computers during patient encounters and
      many still worry that computers will depersonalize their interactions with
      patients. This case study describes patient and clinician reactions to a computer
      based health appraisal system. Findings showed no difference in any aspect of
      patient satisfaction between computer and non-computer groups. Use of a computer
      in the consulting room neither depersonalized nor enhanced patient satisfaction.
      Clinicians (in this case, nurse practitioners and physician assistants) were
      willing to use the system, which they perceived as having benefits for patient
      care, but were concerned about the increased time required for exams, effort
      required to learn the system while still interacting appropriately with the
      patient, increased monitoring of their performance, and other organizational
      issues. Clinicians who used the system showed a higher tolerance for uncertainty
      and communicated more frequently with each other and with others throughout the
      department. Implementation was slowed by the need to demonstrate the monetary
      value of the system.

PMID- 10916587
TI  - Using simulation to educate hospital staff about casemix.
AB  - When the Australian government funded a casemix development program, few hospital
      clinicians or staff knew much about casemix classifications like Diagnosis
      Related Groups (DRGs). Although the concepts behind casemix are essentially
      simple, it is not a trivial task to explain the logic used to assign patients to
      classes, or the use of casemix data for management or funding. Therefore, as part
      of a project to create educational material, a computer-based management game,
      built around a simulation model of a hospital, was developed. The game was
      designed for use in a workshop setting, to allow participants to test their
      understanding of the casemix information presented to them. The simulation
      mimicked the operation of a hospital, with a player taking the role of a hospital
      manager. It aimed to demonstrate how AN-DRGs might be used for funding; how
      patient costs are influenced by hospital activity; and how casemix data can
      assist in monitoring the use of resources. The game, called Dragon, proved to be
      very successful, and is now distributed as part of the National Casemix Education
      series.

PMID- 10916588
TI  - The transformation of the probability of a heart fatality into a queue position.
AB  - The population of Bury and Rochdale has a much higher rate of Coronary Heart
      Disease than the national average. This paper develops an approach, based on the
      Framingham score method, of making patients aware in a lucid manner of their risk
      of suffering a fatal heart attack by assigning them a position in a queue of
      people who are similar to them so far as non-modifiable risk factors are
      concerned.

PMID- 10916589
TI  - Use of a mathematical model to evaluate breast cancer screening policy.
AB  - A model of breast cancer screening was developed, in which the processes of
      tumour origination and growth, detection of tumours at screening, presentation of
      women with cancers to their GP, and of survival after diagnosis were modelled
      parametrically. The model was fitted to data from the North-West of the UK, for
      413 women who screened positive, and for 761 women who developed interval
      cancers. Model validation comprised verification that the final model fitted the
      data adequately, together with the comparison of model predictions with findings
      by other workers. The mathematical model was used to assess different screening
      policies, and to ask "what if" questions. Taking the cost of breast cancer to be
      the sum of the cost of screening and the cost of PYLL (person years of life lost
      due to cancer), the optimal screening policy was calculated. The costs of the
      current policy and of other possible screening policies were found, together with
      their effects on life lost and on mortality. The tentative conclusion was that if
      monies can be found to extend the screening programme, for example to carry out
      one more screen per woman, most benefit would be obtained by reducing the start
      age of screening by 3 years.

PMID- 10916590
TI  - Evaluating screening policies for the early detection of retinopathy in patients
      with non-insulin dependent diabetes.
AB  - Retinopathy is a common complication of insulin-dependent (IDDM) and non-insulin
      dependent (NIDDM) diabetes, but serious visual loss may be prevented or delayed
      with sufficiently early diagnosis and treatment. Screening for early signs of
      retinopathy is clearly beneficial for some people, but there is no established
      consensus about who should be screened, by whom, by what technique and with what
      frequency, especially for NIDDM. The model described in this paper simulates the
      development of eye disease in a population of NIDDM patients and the effects of
      different screening schemes in terms of years of sight saved and the numbers of
      people prevented from suffering severe visual loss. The initial results indicate
      that blanket screening of all NIDDM patients may not be effective.

PMID- 10916591
TI  - Evaluating the costs of alternative options for dementia services.
AB  - In the next decade the number of demented people is likely to increase. This has
      a financial impact on the resources allocated for health and social care.
      Classical methodologies for dealing with dementia include the historic model that
      has been criticised for its poor co-ordination between general practitioners,
      psychiatrists, social workers and the treatment services, and the needs-based
      approach that, although it involves a co-ordinating needs manager, does not
      prevent leapfrogging of patients. In order to overcome these problems we propose
      an annual screening of patients to take place in the needs-based models and
      compare this with a more sophisticated model in which after being screened
      patients are investigated for potential drug treatment. We also consider mix
      intervals for under 75 and over 75. Decision analysis is used to assess the
      different screening options. Assuming a 20% reduction by treatment of the cost of
      care we find optimal the investigation/treatment of all patients after screening.
      Sensitivity analysis shows that even an 8.5% reduction would make the needs-based
      models non-optimal.

PMID- 10916592
TI  - Selecting a decision model for economic evaluation: a case study and review.
AB  - The increased use of modelling techniques as a methodological tool in the
      economic evaluation of health care technologies has, in the main, been limited to
      two approaches--decision trees and Markov chain models. The former are suited to
      modelling simple scenarios that occur over a short time period, whilst Markov
      chain models allow longer time periods to be modelled, in continuous time, where
      the timing of an event is uncertain. In the context of economic evaluation, a
      less well developed technique is discrete event simulation, which may allow even
      greater flexibility. Taking the economic evaluation of adjuvant therapies for
      breast cancer as an illustrative example, the process of building a decision
      tree, a Markov chain model, and a discrete event simulation model are described.
      The potential benefits and problems of each approach are discussed. The
      suitability of the modelling techniques to economic evaluations of health care
      programmes in general is then discussed. This section aims to illustrate the
      areas in which the alternative modelling methods may be most appropriately
      employed.

PMID- 10916593
TI  - A simulation modelling approach to evaluating length of stay, occupancy,
      emptiness and bed blocking in a hospital geriatric department.
AB  - The flow of patients through geriatric hospitals has been previously described in
      terms of acute (short-stay), rehabilitation (medium-stay), and long-stay states
      where the bed occupancy at a census point is modelled by a mixed exponential
      model using BOMPS (Bed Occupancy Modelling and Planning System). In this a
      patient is initially admitted to acute care. The majority of the patients are
      discharged within a few days into their own homes or through death. The rest are
      converted into medium-stay patients where they could stay for a few months and
      thereafter either leave the system or move on to a long-stay compartment where
      they could stay until they die. The model forecasts the average length of stay as
      well as the average number of patients in each state. The average length of stay
      in the acute compartment is artificially high if some would-be long-term patients
      are kept waiting in the short-stay compartment until beds become available in
      long-stay (residential and nursing homes). In this paper we consider the problem
      as a queueing system to assess the effect of blockage on the flow of patients in
      geriatric departments. What-if analysis is used to allow a greater understanding
      of bed requirements and effective utilisation of resources.

PMID- 10916594
TI  - An analysis of admission, discharge and bed occupancy of stroke patients aged 65
      and over in English hospitals.
AB  - Stroke illness is a common problem in the UK. Factors such as incidence, age, and
      ethnicity have already been shown to affect admission patterns and discharge
      outcomes. Our analysis of an English Hospital Episode Statistics database shows
      that weekends and public holidays also influence the admission and discharge
      patterns of elderly stroke patients. We discuss the possible reasons for this.

PMID- 10916595
TI  - A three compartment model of the patient flows in a geriatric department: a
      decision support approach.
AB  - As users of long term geriatric services occupy the beds for prolonged periods of
      time it is important that decision makers understand how clinical and social
      decisions interact to influence long term care costs. A flow modelling approach
      enables us to estimate current inpatient activity and to test different care
      options, thereby optimising decision making. In previous work we developed a two
      compartment model of patient flows within a geriatric hospital, where patients
      are initially admitted to an acute or rehabilitative state from which they either
      are discharged or die or are converted to a long-stay state. Long-stay patients
      are discharged or die at a slower rate. This initial research discussed the use
      of a compartmental model to describe flows through the hospital system. We now
      discuss a three compartment model where the compartments may be described as
      consisting of acute care, rehabilitation and long-stay care. A Markov model is
      then used to count and cost the movements of geriatric patients within a hospital
      system. Such an approach enables health service managers and clinicians to assess
      performance and evaluate the effect of possible changes to the system. By
      attaching costs to various parts of the system we may facilitate the evaluation
      and comparison of different strategies and scenarios. Using the model, we show
      that a geriatric medical service that improved the acute management of in
      patients became more cost-efficient. Hospital planners may thus identify cost
      effective options.

PMID- 10916596
TI  - Decision making support in reshaping hospital medical services.
AB  - "Bed crisis" is a buzz word of the 90's in the National Health Services (NHS).
      Medical emergency admissions keep rising and hospital resources remain limited.
      Faced with such a dilemma, many hospitals have endeavoured to improve their
      service efficiencies in order to meet the challenge. This paper describes a real
      life hospital process re-engineering project in which computer simulation and
      optimisation models were applied to provide decision making support in
      determining the size of the proposed medical assessment unit and the allocation
      of the available medical beds to minimise hospital bed overflows.

PMID- 10916597
TI  - An integer programming model for vaccine procurement and delivery for childhood
      immunization: a pilot study.
AB  - The National Immunization Program of the Centers for Disease Control and
      Prevention has identified several challenges that must be faced in childhood
      immunization programs to deliver and procure vaccines to protect against the
      common preventable diseases. The biomedical challenge is how to combine and
      formulate products to take advantage of new vaccines without requiring additional
      injections. A programmatic challenge is to incorporate then into already crowded
      immunization schedules. The economic challenge is to make wise procurement
      choices from among a growing number of competing products. This paper reports the
      results of a pilot study using operations research methodologies to address the
      third of these challenges. The pilot is an integer programming model for
      procuring vaccines for a set of childhood diseases. The model is studied under
      various scenarios (minimum total cost, next lowest total cost, maximum total
      cost, minimum total cost with all manufacturers represented). The results of this
      pilot study demonstrate how a practical set of operations research tools can be
      developed to guide vaccine selection and procurement, which might stimulate the
      development of innovations in new vaccines to meet the challenges of disease
      control through immunization.

PMID- 10916598
TI  - Productivity and efficiency changes in primary care: a Malmquist index approach.
AB  - The reforms of the National Health System in the UK introduced in 1990 led to
      substantial changes in the organisation of primary health care. In this paper we
      analyse the efficiency of primary care provision in the English Family Health
      Service Authorities (FHSAs) over the period 1990/91-1994/95. We use Data
      Envelopment Analysis to measure Malmquist indices of productivity changes, which
      are then decomposed into indices of pure technical efficiency change, scale
      efficiency change and technological change. The analysis indicates a small
      improvement in the productivity over the period considered. The increase is
      attributed to pure technical efficiency improvement and positive change in scale
      efficiency, while the technology does not show significant change. The analysis
      suggests that there is very limited scope for productivity gains in this sector.

PMID- 10916599
TI  - Improving on-time performance in health care organizations: a case study.
AB  - In this paper, we propose a strategy to build a measurement system that helps
      improve on-time performance in health care organizations. We analyze the
      measurement system for monitoring the performance of daily start times of first
      surgeries in a U.S. hospital. Although surgeons appear to be the main cause of
      delay, efforts to improve their on-time performance alone are not sufficient to
      improve on-time performance for first surgeries. Therefore, working on the main
      source of delay to improve performance, as the Pareto principle suggests, does
      not always work in the health care context. Rather, we found that ameliorating
      the hospital's overall on-time performance achieves the desired result of
      improving surgeons' performance through a snowball effect (a self-reinforcing
      effect) and, consequently, the on-time performance for first surgeries also
      improves.

PMID- 10916600
TI  - When should pharmacists visit their wards? An application of simulation to
      planning hospital pharmacy services.
AB  - This paper reports a pilot study of the use of simulation in planning hospital
      pharmacy services. The objectives were to create a simulation model of the
      hospital drug distribution system, to use the model to investigate a simple
      problem and to assess the potential for simulation to aid decision making in
      hospital pharmacy management. The problem chosen for investigation focused on the
      UK ward pharmacy system, where a pharmacist visits each ward daily to initiate
      the supply of newly prescribed non-stock medication. A simulation model was used
      to investigate how changing the time of the ward pharmacist's visit could affect
      the mean time delay between the prescription of a non-stock drug and the arrival
      of that drug on the ward. The simulation results suggest that the time of day at
      which pharmacists visit their wards can have a major impact on delay times, and
      that the relative benefit of different visit times is likely to vary between
      wards. Simulation was found to be a useful approach to investigating different
      service alternatives without the expense and disruption of assessing each in
      practice.

PMID- 10916601
TI  - Strategic adaptation of US rural hospitals during an era of limited financial
      resources: a longitudinal study, 1983 to 1993.
AB  - This research investigated the competing effects of environmental and
      organizational pressures on rural hospitals' revenue-enhancing and cost
      containment strategies from 1993 to 1993. In general, organizational pressures
      (multihospital system membership and non-government control) exerted more
      influence than environmental ones. Also, strategies generally were sustained over
      time and were particularly interdependent with hospitals' maintenance of staffed
      beds. Strategies did respond to environmental pressures, however, with revenue
      enhancement associated with local market competition and munificence, and cost
      containment associated with pressures from Medicare reimbursement.

PMID- 10916602
TI  - A healthcare staff decision model considering the effects of staff cross
      training.
AB  - In this study a staff planning model for a health service clinic has been
      developed and validated using an example case of a health service clinic. The
      primary purpose of this research is to develop a representative staff planning
      model which balances the cost and benefits of staff task flexibility through
      cross-training for a healthcare facility. Additionally, legal requirements for
      task substitution in the healthcare industry have been considered in the model.

PMID- 10916603
TI  - Impact of internal and external environmental pressures on hospital inefficiency.
AB  - This study used stochastic frontier analysis to study variations in inefficiency
      in US hospitals. Cost-inefficiency (i.e., differences between best practice and
      actual expenses) is assumed to be affected by ownership status, competition,
      regulatory pressure, and market demand conditions. The level of analysis is the
      hospital (n = 3,262) and data for 1994 were used. The market was defined as the
      county in which the hospital was located. A two-stage approach was used in the
      analysis. In the first stage, translog cost-functions were estimated. Outputs
      used in the cost function analysis include inpatient discharges, post-admission
      days, outpatient visits, medical education, and case-mix index. Following
      Jondrow's technique, inefficiency scores (i.e., the difference between predicted
      least costs and actual costs) were estimated. Inefficiency estimates were not
      sensitive to changes in assumptions about the distribution of the error term. In
      the second stage, the estimated inefficiency scores were used as dependent
      variables to test hypotheses about the impact of internal and external
      environmental pressures on cost-inefficiency. Since the distribution of the
      estimated inefficiency scores was censored, Tobit equations were estimated. The
      second stage analysis found that measured inefficiency was negatively related
      with industry concentration (Herfindahl index), public payment policy, and
      unemployment rate and positively related with for-profit status.

PMID- 10916604
TI  - The impact of the internal market on hospital efficiency, productivity and
      service quality.
AB  - In this paper we use non-parametric mathematical programming models to compute
      and decompose Malmquist indices of productivity and quality change, which are
      used to evaluate the reforms in the UK National Health Service in the early
      nineties. We focus on acute hospitals and we study them over the first five years
      of the reforms. The findings of the study indicate that there was a productivity
      slowdown in the first year after the reforms but productivity progress in the
      subsequent years and thus, overall there was a net gain in productivity over the
      entire period considered. Productivity trends were dominated by technical change
      rather than hospital relative efficiency changes, as hospitals were already
      largely relatively efficient at the time of the introduction of the reforms. In
      fact, over the last four years in the period studied there was small relative
      efficiency regress and this does not bear out the argument that the reforms would
      increase hospital efficiency. The productivity changes are similar when service
      quality is incorporated in the analysis but the magnitude of these changes
      diminishes. Quality of service followed different trends to productivity change
      and this may have been the price for the productivity gains achieved.

PMID- 10916605
TI  - Patient flows and optimal health-care resource allocation at the macro-level: a
      dynamic linear programming approach.
AB  - In this paper we present a deterministic allocation model in which a patient's
      health-state changes due to health-care interventions. This change in a patient's
      health-state has a direct effect on the patient's expected future need for health
      care. Hence, current allocation decisions determine to some extent the set of
      possible allocation decisions in the future. In order to take this into account
      we have formulated a dynamic linear programming version of a patient-flow system.
      This enables us to describe the effects of using different objective functions on
      the optimum level and composition of the provision of health services within
      given resource constraints. The linear programming approach enables the
      quantification of the health effects and therefore the desirability of the (re
      )allocation of health-care resources. We provide some simulation results in order
      to illustrate the working of the model.

PMID- 10916606
TI  - A descriptive assessment of the production and cost efficiency of general
      hospitals in Greece.
AB  - This paper focuses on the assessment of alternative aspects of the efficiency of
      98 out of 126 hospitals of the Greek national health system. The analysis is
      directly concerned with the degree of utilisation of resources and the production
      efficiency of the general hospitals selected. For the measurement of the indices
      of efficiency, the internationally known method of Data Envelopment Analysis
      (modified to the particular characteristics of the Greek NHS) was used. The
      efficiency of Greek hospitals was assessed utilising two alternative conceptual
      models: one focusing on production and the other on cost efficiency. The results,
      in both cases, indicated the scope for substantial efficiency improvements. The
      analysis has sought to discuss the policy implications resulting from the current
      efficiency status of the hospitals with reference to issues of resource re
      allocation and optimal scale size.

PMID- 10916607
TI  - Has DRG payment influenced the technical efficiency and productivity of
      diagnostic technologies in Portuguese public hospitals? An empirical analysis
      using parametric and non-parametric methods.
AB  - The use of Diagnosis Related Groups (DRG) as a mechanism for hospital financing
      is a currently debated topic in Portugal. The DRG system was scheduled to be
      initiated by the Health Ministry of Portugal on January 1, 1990 as an instrument
      for the allocation of public hospital budgets funded by the National Health
      Service (NHS), and as a method of payment for other third party payers (e.g.,
      Public Employees (ADSE), private insurers, etc.). Based on experience from other
      countries such as the United States, it was expected that implementation of this
      system would result in more efficient hospital resource utilisation and a more
      equitable distribution of hospital budgets. However, in order to minimise the
      potentially adverse financial impact on hospitals, the Portuguese Health Ministry
      decided to gradually phase in the use of the DRG system for budget allocation by
      using blended hospital-specific and national DRG case-mix rates. Since
      implementation in 1990, the percentage of each hospital's budget based on
      hospital specific costs was to decrease, while the percentage based on DRG case
      mix was to increase. This was scheduled to continue until 1995 when the plan
      called for allocating yearly budgets on a 50% national and 50% hospital-specific
      cost basis. While all other non-NHS third party payers are currently paying based
      on DRGs, the adoption of DRG case-mix as a National Health Service budget setting
      tool has been slower than anticipated. There is now some argument in both the
      political and academic communities as to the appropriateness of DRGs as a budget
      setting criterion as well as to their impact on hospital efficiency in Portugal.
      This paper uses a two-stage procedure to assess the impact of actual DRG payment
      on the productivity (through its components, i.e., technological change and
      technical efficiency change) of diagnostic technology in Portuguese hospitals
      during the years 1992-1994, using both parametric and non-parametric frontier
      models. We find evidence that the DRG payment system does appear to have had a
      positive impact on productivity and technical efficiency of some commonly
      employed diagnostic technologies in Portugal during this time span.

PMID- 10916608
TI  - A signalling theory of excessive technological adoption.
AB  - Technology adoption has been identified as one of the main elements behind the
      growth of health care expenditures. It has been argued that the health insurance
      arrangements in the US justify, to a certain extent, the technology-driven rise
      in costs. Moreover, it eases the adoption of less cost-effective procedures and
      devices. This paper presents an additional argument by which excessive technology
      investments may occur: providers of care invest in technology as a way to
      "signal" their intrinsic (and unobservable) quality. Providers face the option of
      adopting a new technology. The decision of adoption in itself may convey
      information about his/her quality: for example, patients conjecture that
      providers who display newer technology are of higher quality. Providers, being
      aware of this, may invest in technology to reveal themselves as high quality.
      Thus, technology adoption could result only from the desire to attract patients.
      The investment is self-defeating in the sense that if all providers invest, no
      information about quality is transmitted to patients. We evaluate the argument in
      a context of demand for health care services where patients have initially no
      information about the quality of different providers. We show that an incentive
      to invest as a way to signal quality may or may not lead to overinvestment. It is
      also possible that only some providers invest. They reveal themselves as high
      quality providers. The analysis suggests that the argument is more important for
      some services than for others. Overall, an additional argument for overinvestment
      in technology in some circumstances is provided.

PMID- 10916609
TI  - Naegleria fowleri: a free living amoeba of emerging medical importance.
AB  - Naegleria fowleri, a free-living amoeba is ubiquitous and word-wide in
      distribution. Infection is due to inhalation or aspiration of aerosols containing
      cysts found in the environment. Of late, the amoeba is emerging as a pathogen of
      medical importance causing primary amoebic meningoencephalitis (PAM) in humans.
      The diagnosis of the condition is mainly parasitic which depends on the detection
      and identification of Naegleria trophozoites in the cerebro-spinal fluid (CSF) or
      biopsied brain tissue. Serological tests are not useful in the diagnosis of PAM.
      Most cases are fatal and various amoebicidal agents have been tried
      unsuccessfully. The present paper provides a review of the recent information on
      the biology and epidemiology of the disease caused by the amoeba Approaches in
      the diagnosis, pathophysiology and treatment of the condition are also discussed.

PMID- 10916610
TI  - Isolation of verotoxin producing Escherichia coli from diarrhoeal and urinary
      tract infection patients.
AB  - Fourty nine Escherichia coli strains, isolated from diarrhoeal and urinary tract
      infection (UTI) patients, attending Bareilly district hospital, Uttar Pradesh
      during October to December, 1998 were screened for verotoxin (VT) production by
      Vero cell assay. Five strains produced characteristic cytopathic effect on Vero
      cell line, of which 4 were from diarrhoeal and one was from UTI-patient. The
      level of VT-production varied widely. Antibiotic sensitivity tests revealed that
      the VT-producing E. coli (VTEC) were mostly sensitive to kanamycin, norfloxacin
      and nalidixic acid but resistant to ampicillin and tetracycline.

PMID- 10916611
TI  - In vitro effects of three metallic salts and soot on the growth of five species
      of the dermatophytes.
AB  - The antifungal effects of zinc chloride (znCl), Calcium chloride (CaCl),
      magnesium chloride (MgCl) as well as soot collected from a local kitchens were
      tested on five isolated species of the dermatophytes from cases of human
      dermatophytoses. Of these three metallic salts, ZnCl showed the highest
      inhibitory effect on the dermatophytes. At a concentration of 0.01 M it showed
      100% inhibition on these fungi. Although the other two metallic salts showed some
      inhibitory effect CaCl at concentration between 0.01 M and 1 M showed only 50%
      inhibitory effect while MgCl at concentration between 0.1 M and 1 M showed less
      than 50% inhibitory effect on the fungi. Also soot inhibited the growth of all
      the dermatophytes tested at concentration between 0.1 and 2%. Trichophyton rubrum
      and Microspum audouinii appeared to be most sensitive to these compounds compared
      to the other three species which include T. mentagrophytes, T. tonsurans and M.
      gypseum.

PMID- 10916612
TI  - Clinical spectrum of bacteroidaceae in a tertiary care hospital.
AB  - Members of Bacteroidaceae family are the most commonly isolated anaerobic
      pathogens in humans. This study summarises our experience of isolation and
      antimicrobial susceptibility pattern of these anaerobes from diverse clinical
      infections in a tertiary care hospital. Over a period of 5 years, 611 samples
      were received for anaerobic culture. Of these, 53 specimens yielded 62 anaerobic
      isolates. Thirty of the 62 isolates (48.4%) belonged to Bacteroidacea family
      obtained from 29 patients. They comprised of 14 (14/32; 43.7%) Prevotella spp.,
      13 (13/32; 40.6%) Bacteroides spp., 3 (3/32; 9.3%) Porphyromonas spp and
      Fusobacterium (2/32; 6.2%). In 14 of 27 patients (48%) the infection was
      polymicrobial. All the isolated strains were sensitive to metronidazole. This
      study highlights need for adopting anaerobic culture technique as a routine
      diagnostic procedure and constant monitoring of antimicrobial susceptibility of
      all anaerobic isolates.

PMID- 10916613
TI  - Prevalence of resistant Staphylococcus aureus at Aurangabad.
AB  - Seven hundred and eighty three isolates of Staphylococcus aureus isolated from
      pus (586), blood (78), sputum (25), urine (23), cerebrospinal fluid (23) and
      various other body fluids (48) were subjected to in-vitro antimicrobial
      susceptibility testing by modified Kirby-Bauer method. Almost all the isolates
      were resistant to penicillin (99.62 per cent) and ampicillin (99.62 per cent).
      Resistance to erythromycin, tetracycline and cotrimoxazole was observed in 88.5,
      87.62, and 80.85 per cent isolates respectively. Resistance to gentamicin was
      68.32 per cent. Resistance to most of the commonly used antimicrobial agents
      indicates a need to replace these drugs with other agents and maintenance of
      surveillance to detect changing patterns of resistance.

PMID- 10916614
TI  - Susceptibility of Phlebotomus argentipes and P. papatasi (Diptera: Psychodidae)
      to insecticides.
AB  - Field collected fully fed adults of Phlebotomus argentipes and P. papatasi were
      screened in the laboratory for susceptibility to DDT, BHC, malathion,
      deltamethrin, permethrin, lambdacyhalothrin and bendiocarb. Pondichery strain of
      P. papatasi and P. argentipes showed variations in their susceptibility to
      insecticides. Both the species were resistant to permethrin but tolerant to DDT
      and malathion with LD99.99 values of 13.88, 1.92, 1.08 and 34.63, 4.69, 16.32
      times more than the deterministic doses respectively. However, they were
      susceptible to bendiocarb with LD99.99 7.6 and 1.6 times lower than the
      deterministic doses. While P. papatasi was susceptible to BHC, P. argentipes
      showed tolerance (1.6 times). The former showed tolerance to deltamethrin and the
      latter exhibited resistance (34 times). It was reverse in case of
      lamdacyhalothrin. High susceptibility of the vector sandflies to bendiocarb
      suggests that this insecticide could be used effectively against OP and
      pyrethroid resistant populations for Kalaazar control.

PMID- 10916616
TI  - Aedes aegypti (L) in Port Blair, Andaman and Nicobar islands-distribution and
      larval ecology.
AB  - A comprehensive survey was carried out in the Port Blair town in Andaman and
      Nicobar islands, in order to study the distribution and relative prevalence of
      Aedes aegypti during the monsoon (July'1997-October'1997) season using larval
      survey and adult collection methods. Ae. aegypti was found in all 21 localities
      surveyed. Spatial variations in distribution was evident which was closely
      related to population density. The nature of the larval habitats was observed to
      be similar in all the localities. For both outdoor and in-door containers,
      breeding preference ratio was highest for mud/brick/cement containers, followed
      by metal and plastic containers. These findings are correlated with water storage
      habits of the residents in the localities surveyed.

PMID- 10916615
TI  - Changing aetiology of urinary tract infections and emergence of drug resistance
      as a major problem.
AB  - A study was undertaken to ascertain the spectrum of causative agents responsible
      for UTI and to detect the magnitude of anti microbial resistance in aetiological
      agents. Klebsiella species caused urinary tract infection in maximum number of
      cases (124, 37.35%) followed by Escherichia coli (114, 34.4%), Pseudomonas
      aeruginosa 32 (9.64%) and Staphylococcus aureus 23 (6.93%). Other organisms
      caused urinary tract infection in 39 (11.75%) cases. Resistance to gentamicin was
      observed in 83% S. aureus, 84.7% Klebsiella species, 78.1% Escherichia coli,
      71.9% Pseudomonas aeruginosa and 94.8% of remaining isolates. A large number of
      isolates (> 90%) were resistant to ampicillin, Cotrimoxazole erythromycin, and
      chloramphenicol. All the isolates of S.aureus were resistant to penicillin. This
      observations indicate extremely high degree of resistance in urinary pathogen and
      warrant change in antibiotic usage as well as formulation of policy for rational
      use of antibiotics.

PMID- 10916617
TI  - Use of mycelial suspension and metabolites of Paecilomyces lilacinus (Fungi:
      Hyphomycetes) in control of Aedes aegypti larvae.
AB  - Mycelial suspension of possible was assessed to examine its Paecilomyces
      lilanicus, a fungus, detrimental effects on fourth instar larvae of Aedes
      aegypti. The immature stages suffered 64-68% mortality with 0.5-1% mycelial
      suspension. There was 12-16% adult emergence which was statistically significant
      (P < 001). Czapeckdox and PYG media metabolites were used against the third
      instar larvae in various concentrations. The effects were evaluated on several
      parameters like mortality, mean survival time and time taken for adult emergence.
      The results indicate that the fungus does not producae any toxic metabolites.

PMID- 10916619
TI  - HBsAg positivity among different high risk groups and low risk group individuals
      in Calcutta.

PMID- 10916618
TI  - Intracameral gnathostomiasins: a first case report from Pondicherry.
AB  - In this communication, a first case of intracameral gnathostomiasis in a 34 years
      old woman in Pondicherry and its successful surgical removal is reported. The
      clinical presentation and epidemiology of the disease are discussed.

PMID- 10916620
TI  - Clinico-epidemiological study on leptospirosis in certain parts of north-eastern
      region.

PMID- 10916621
TI  - Increased mosquito-breeding activity in Mysore University Campus Manasagangoti
      Karnatka.

PMID- 10916622
TI  - Nutrition and clinical outcome in peritoneal dialysis patients.

PMID- 10916623
TI  - Development and progression of diabetic nephropathy: future interventions.

PMID- 10916624
TI  - [Specificity of the diabetic nephropathy in patients with type 1 diabetes
      mellitus].

PMID- 10916625
TI  - [The importance of metabolic control in type 2 diabetes mellitus].

PMID- 10916626
TI  - [Diabetic nephropathy in patients with type 2 diabetes mellitus].

PMID- 10916627
TI  - [Pharmacological treatment of hypertension in diabetes mellitus].

PMID- 10916628
TI  - [Diabetic nephropathy as a cause of terminal kidney failure in Poland].

PMID- 10916629
TI  - [Kidney or kidney and pancreas transplantation in patients with diabetic
      nephropathy].

PMID- 10916630
TI  - [Sodium sensitive and non sodium sensitive arterial hypertension].

PMID- 10916631
TI  - [Hypertensive nephropathy].

PMID- 10916632
TI  - [Hypertension in the course of renal diseases].

PMID- 10916633
TI  - [50 years of recurrence].
AB  - 50 years of practice in orthodontics! The calling-up of the past raises old
      conceptions of orthodontics, full of illusions on its real possibilities and
      placed under the dictatorship of Pont's index. Some years later, the american
      technics were brought to France, and progressively took advantage on functional
      methods. From 1981, a series of studies conducted by Little shows the frequency
      of relapses after excellent treatments. It is clear that orthodontics could not
      survive if it was confirmed that it has only a temporarily effect. Different
      causes of relapses are examined: some particular effects of facial growth, the
      use of over-correction and pre-formed materials, the lack of occlusal
      equilibration by reshaping, the neglecting of periodontal reactions, the
      incorrect application of rules of contention. But the fundamental cause of
      instability of treatments observed by Little, is it not that these treatments
      have been performed in agreement with the concepts of the years 1950-1960, that
      is to say more determined by a geometrical representation of the face, and a
      mechanical conception of the treatment, rather than been guided by a good
      comprehension of the physiology of the patient?

PMID- 10916634
TI  - [Rapid maxillary expansion: presentation of 3 clinical cases].
AB  - The use of rapid palatal expansion (RPE) escalates greatly in routine clinical
      practice. The most commonly recognized indication for rapid palatal expansion is
      the correction of a posterior crossbite. RPE is produced by applying a lateral
      force against the posterior maxillary dentition, producing a separation of the
      midpalatal suture and its remodeling. The clinical consequence of such a change
      is an increase in total arch length. That will allow the accommodation of
      impacted, rotated or displaced teeth into the dental arch. This additional arch
      length may lead to an overall reduction in the number of patients who undergo
      extraction due to tooth size-arch size discrepancies. RPE also can be used for
      preparation for functional jaw orthopedics or orthognathic surgery. Generally,
      RPE appliances are fixed and there are two types of expanders: the Haas-type and
      the Hyrax-type rapid palatal expanders. This clinical article presents three
      cases of rapid palatal expansion and their results.

PMID- 10916635
TI  - [Recurrence].
AB  - Relapse is a multi-factorial phenomenon to which, in the absence of universally
      accepted finishing criteria, each practitioner tries to oppose through some
      references which he is closely following to. The author lists his personal
      references.

PMID- 10916636
TI  - [Orthodontics, stability, recurrence].
AB  - The stability of orthopedic treatments has been studied in many ways, but
      conclusions are very divergent. Usually, the methodology is not reproducible and
      unfavourable to compare the results. The structural analysis, described by
      Lautou, Dunglas and Vermelin, help to distinguish the skeletal from the dental
      effects, during treatments using activators. Clinical cases treated with
      activator appliances show that the relapse appears when the orthopedic response
      is poor and when the dento-alveolar compensations are strong.

PMID- 10916637
TI  - [Nasal respiration and recurrence].
AB  - Cause and effect relationships existing between "nasal breathing impairment" and
      "relapse" have inherited from controversies which have animated the debate
      between the different schools of orthodontics for more than a century. Those
      differences of opinion seem to have their origin in the lack of accuracy inherent
      with the general acceptance of the two concepts of "normal nasal ventilation" and
      "relapse". Rather than retracing their history, we would like to put forward a
      few proposals aimed at getting rid of the doubtful trouble the present difficulty
      confronts us with. We have therefore endeavored: 1. to define most exactly our
      concepts of "optimal nasal ventilation" and "relapse"; 2. to determine,
      afterwards, the mechanics responsible for facial shape alterations due to nasal
      obstruction; 3. hence, to deduce the therapeutic behavior enabling us to master
      those alterations more extensively. Bearing in mind that, in order to legitimate
      the risk of a treatment, acknowledge its benefit and justify its cost (which may
      become prohibitive because of relapse), the clinician has to base his options on
      a body of consistent arguments.

PMID- 10916638
TI  - [Etiopathogenesis of nasal obstruction in children].
AB  - The author lists the dysmorphic and dysfunctional causes of nasal obstruction in
      the child.

PMID- 10916639
TI  - [3D cephalometry].
AB  - The Cepha3DT software is used to generate a 3D model of the human face.

PMID- 10916641
TI  - Invariant elastic constants and eigentensors of orthorhombic, tetragonal,
      hexagonal and cubic crystalline media
AB  - The purpose of this paper is to present a simple and direct way of determining
      the eigenvalues and eigentensors, as well as their orientations, for all crystals
      of the orthorhombic, tetragonal, hexagonal and cubic symmetries, a procedure
      based on the spectral decomposition of the compliance and stiffness fourth-rank
      tensors. First, both the eigenvalues and the idempotent fourth-rank tensors are
      derived for the orthorhombic and tetragonal-7 symmetries. The latter decompose,
      respectively, the second-rank symmetric tensor spaces of orthorhombic and
      tetragonal-7 media into orthogonal subspaces, consisting of the stress and strain
      eigentensors, and split the elastic potential into distinct noninteracting strain
      energy parts. Accordingly, the spectrum of the compliance tensor of the
      tetragonal-6 symmetry is evaluated, by reduction of the eigenvalues and
      eigentensors of either the orthorhombic or tetragonal-7 symmetry. These results
      are, then, applied in turn to each of the hexagonal and cubic crystal systems. In
      each case, the eigenvalues, the idempotent tensors and the stress and strain
      eigentensors are easily derived as particular cases of the results obtained for
      the tetragonal-6 symmetry. Furthermore, it is noted that the positivity of the
      eigenvalues for each symmetry is equivalent to the positive definiteness of the
      elastic potential and, thus, necessary and sufficient conditions are acquired, in
      terms of the compliance-tensor components, characteristic of each symmetry.

PMID- 10916640
TI  - [Changes in the enamel after in vitro debonding of brackets bonded with a
      modified glass ionomer cement].
AB  - The aim of this study was to assess the incidence on the enamel behavior of
      debonding two types of orthodontic brackets, bonded with two different adhesives.
      Ninety recently extracted human premolars were bonded with two types of brackets
      (30 Minitrim and 60 Discovery). Two bonding protocols were used. The first one
      consisted in bonding 30 Minitrim and 30 Discovery brackets on etched and dried
      enamel surfaces with No Mix orthodontic resin. The second one consisted in
      bonding 30 Discovery brackets on unetched and wet enamel surfaces with a modified
      glass ionomer cement, Fuji Ortho LC. Teeth were stored in hydrated ambiance at 37
      degrees C for 7 days before debonding. A LLOYD (LR 30K) testing machine was used
      to evaluate the orthogonal tensile bond strength. The debonded base brackets were
      examined with a scanning electron microscope (JEOL JSM 6400) and qualitatively
      analyzed with an OXFORD-LINK-ISIS to assess the site of bond failure and the
      enamel detachments. An Enamel Detachment Index (EDI) was defined. The results
      showed that the types of orthodontics brackets and adhesives influenced the bond
      strength and the enamel detachment. The Discovery/No Mix couple presented higher
      bond strength (214.9 N) than observed with the Discovery/Fuji Ortho LC (98.5 N)
      or the Minitrim/No Mix (82.3 N) couples. The surfaces of enamel detachment were
      insignificant and not extended for all brackets. Nevertheless, the Discovery/No
      Mix couple presented 42% of an EDI score of 1, compared to the Discovery/Fuji
      Ortho LC and Minitrim/No Mix couples which presented, respectively, 8% an 20% of
      an EDI score of 1. The laser sculpted base (Discovery) bonded on unetched and wet
      enamel surfaces with the modified glass ionomer cement (Fuji Ortho LC) offers a
      good resistance to debonding forces and preserve enamel integrity.

PMID- 10916642
TI  - On the origin of topological differences between experimental and theoretical
      crystal charge densities
AB  - Topological analysis of experimental and theoretical (molecular and crystal)
      electron densities of p-nitroaniline and p-amino-p'-nitrobiphenyl reveals
      considerable discrepancies between experiment and theory for the bond critical
      points properties. Particularly large differences occur for the positive
      curvature along the bond path (lambda 3). The differences become somewhat smaller
      when more extended basis sets and correlation effects are introduced in the
      theoretical calculations. The effect of the crystal matrix on the properties of
      bond critical points is evaluated for the p-nitroaniline molecule using the 6
      21G** and 6-31G** basis sets. The differences between the isolated molecule and
      the molecule in the crystal are too small to explain the quantitative
      disagreement between the theoretical and experimental topologies reported in the
      literature and found in the current study. For most bonds, the observed changes
      in the properties of the electron density agree well for both basis sets but some
      discrepancies are found for changes in lambda 3 for N-H and aromatic C-C bonds.
      When the theoretical densities are projected into the multipole density functions
      through refinement of the theoretical structure factors, the topological
      properties change and differences between theory and experiment are reduced. The
      main origin of the observed discrepancies is attributed to the nature of the
      radial functions in the experimental multipole model.

PMID- 10916644
TI  - Diffuse X-ray scattering and disorder in p-methyl-N-(p-chlorobenzylidene)aniline,
      C14H12ClN (ClMe): analysis via automatic refinement of a Monte Carlo model
AB  - A recently developed method for fitting a Monte Carlo computer simulation model
      to observed single-crystal diffuse X-ray scattering has been applied to (h0l)
      scattering data obtained for the disordered compound p-methyl-N-(p
      chlorobenzylidene)aniline, C14H12ClN (ClMe), at 295 K. Each molecular site is
      occupied by a molecule in one of four basically different orientations defined by
      combinations of a side-to-side and an end-to-end flip. These different
      orientations were represented in the model by two sets of binary random
      variables. In addition to these occupancy variables, the model also allowed local
      orientational and centre-of-mass translational displacements. The disordered
      structure was modelled using rigid-body molecules linked by harmonic springs to
      represent 'effective' intermolecular interactions. The refined model included 4
      parameters describing the correlation of neighbouring occupational variables and
      28 parameters describing the force-constant and 'size-effect' parameters on seven
      symmetry-inequivalent types of intermolecular vectors. The model refined to an
      overall agreement factor, [formula: see text], of 32.8% for 28,500 data points.
      It was found that the SRO correlation structure observed within the layers of
      molecules in the ab plane is typical of a frustrated lattice, where nearest- and
      second-nearest-neighbour effects oppose each other. This appears to be the main
      difference between this compound and the sister compound, p-chloro-N-(p
      methylbenzylidene)aniline (MeCl), studied previously. The local relaxational
      displacements that result from local 'size-effect' strains operating on different
      intermolecular vectors generally reflect the tendency for distances involving Cl
      Cl interactions to be longer than the observed average distances.

PMID- 10916643
TI  - Resonant X-ray diffraction: 'forbidden' Bragg reflections induced by thermal
      vibrations and point defects
AB  - In general, the local atomic environment becomes less symmetric owing to point
      defects and thermal vibrations of atoms in crystals. It is shown that, as a
      result of this phenomenon, an additional anisotropy of the resonant scattering
      factors can occur and the forbidden Bragg reflections can be excited near
      absorption edges. Examples of crystals are presented (Ge, K2CrO4, C-15 type)
      where such thermal-motion-induced (TMI) and point-defect-induced (PDI)
      reflections can be observed. The tensor structure factors of both types of
      reflection are computed. Owing to their resonant character, the PDI reflections
      allow both impurity atoms and host atoms of different types to be studied
      separately. The considered phenomena can provide a very sensitive method to study
      point defects because only the atoms distorted by defects produce contributions
      to the PDI reflections.

PMID- 10916645
TI  - Distinction of space groups (I23 and I2(1)3) and (I222 and I2(1)2(1)2(1)) using
      coherent convergent-beam electron diffraction
AB  - Convergent-beam electron diffraction (CBED) is well known as a powerful tool to
      determine space groups of crystals. However, it cannot distinguish several sets
      of space groups. It is shown theoretically that the coherent CBED method can
      distinguish between space groups (I23 and I2(1)3) and between (I222 and
      I2(1)2(1)2(1)), which belong to indistinguishable sets. It is demonstrated by
      computer simulations that the relative arrangement of 2-fold-rotation and 2(1)
      screw axes can be distinguished by examining the relative phases of specific
      reflections through the interference fringes of coherent CBED patterns. This fact
      implies that these space groups can be distinguished by the coherent CBED method.

PMID- 10916646
TI  - Subperiodic groups isomorphic to factor groups of reducible space groups
AB  - A relationship exists between factor groups of space groups and subperiodic
      groups. This relationship, an isomorphism between factor groups of reducible
      space groups and subperiodic groups, can be used in the derivation of higher
      dimensional space groups, of lattices of space groups, and of irreducible
      representations of space groups. Tables of the layer and rod subperiodic groups
      isomorphic to factor groups of reducible space groups are explicitly given. The
      manifestation of this relationship, in terms of the symmetry diagrams of space
      groups and subperiodic groups, is also discussed.

PMID- 10916647
TI  - Connectivity properties of high-density regions and ab initio phasing at low
      resolution.
AB  - It is expected that a correctly phased low-resolution synthesis would show a set
      of isolated 'blobs' located near to the centres of the macromolecules if the
      corresponding cut-off level is chosen properly. This is not always the case when
      using experimentally measured structure-factor magnitudes. Nevertheless, this
      property can be efficiently used as a constraint in the low-resolution ab initio
      phasing of structure factors. The suggested procedure consists in generating a
      large number of random phase sets, selecting those that together with the
      observed magnitudes result in the desired number of blobs in Fourier syntheses,
      and averaging the selected phase sets. The current paper discusses the formal
      definitions, analysis of low-resolution syntheses, some phasing algorithms and
      their application to ab initio phasing.

PMID- 10916648
TI  - Elucidation of simple pathways for reconstructive phase transitions using
      periodic equi-surface (PES) descriptors. The silica phase system. I. Quartz
      tridymite
AB  - A method of estimating short topological pathways for solid-solid reconstructive
      phase transitions is proposed. To screen the simplest pathways out of the
      infinite manifold in configurational space, a Fourier function approach is used,
      based on periodic nodal (PNS) and periodic equi-surface (PES) descriptors. The
      simplicity of the chosen functions representing the structures in question and
      the linear transition approach provide for most simple relevant transition
      models. Here it is shown that the tetrahedral networks of quartz and tridymite
      are represented topologically and transformed into each other by this approach. A
      trigonal network related to alpha-ThSi2 and B2O3 appears as intermediate during
      the transition model of the periodic functions. The transition path found in this
      way seems to be of exciting directness and of fundamental topological interest.
      The presented approach is not restricted to this specific case and is expected to
      be applicable to a wide variety of reconstructive phase transitions of solids.

PMID- 10916649
TI  - The phenomenon of polarization suppression of X-ray Umweg multiple waves in
      crystals
AB  - The phenomenon of the polarization suppression of X-ray Umweg multiple waves in
      Renninger scans [Renninger (1937). Z. Kristallogr. 97, 107-121] of crystals,
      showing intensity decrease due to properly chosen wavelength and polarization of
      incident radiation, is observed. That is, one of the participating wave
      components in the multiple-wave interference is reduced considerably so that the
      intensity of multiple diffraction is decreased. The condition for total
      suppression of the multiple-wave interaction in crystals is derived theoretically
      from the Born approximation and verified with exact dynamical calculation and
      experiments. Partial suppression of the strong Umweg interfered component is
      demonstrated using elliptically or linearly polarized synchrotron radiation. The
      suppressed multiple-wave intensity distribution reveals high sensitivity to X-ray
      reflection phase. This multiple-diffraction technique under partial polarization
      suppression provides an alternative way of enhancing the visibility of multiple
      wave interference in crystals for direct phase determination.

PMID- 10916650
TI  - [Percutaneous mitral commissurotomy: final departure of the balloon?].

PMID- 10916651
TI  - [Percutaneous mitral commissurotomy by metallic dilator. Multicenter experience
      with 500 patients].
AB  - A clinical investigation has been conducted since January 1996 with a new valve
      dilator for percutaneous treatment of mitral stenosis: metallic commissurotome.
      This new technique is based on the principle of surgical commissurotome but, in
      its mechanism of action, differs from the usual techniques with balloon
      catheters. It also offers the unique possibility for multiple utilizations of the
      same device after resterilization. This article reports a multicenter
      international investigation involving 500 patients, mean age of 34 +/- 13 years,
      with a isolated mitral stenosis and an echography score of 7.7 +/- 1.9. Our
      technique has been feasible in 489 cases (98%) with a success rate (mitral area >
      1.5 cm2 without MR > grade 2) of 93%. The transmitral gradient has diminished
      from 20 +/- 8 mmHg to 4 +/- 3 mm Hg and the mitral area (assessed by planimetry
      at 24 hrs) has increased from 0.91 +/- 0.20 to 2.12 +/- 0.34 cm2. Complications
      were uncommon (13 patients: 2.6%) and consisted in 6 tamponades, 5 mitral
      insufficiencies (one patient required an emergency valve replacement) and 2
      neurological transient accidents. The outcomes of this clinical investigation
      appear most encouraging and at least comparable to those being reported with the
      commonly used techniques. The most serious complications appear to be closely
      related to the level of experience with this technique. Considering the
      possibility to reutilize the metal segments of the apparatus, this technique
      notably reduces the cost of the procedure per patient and it represents a
      significant benefit in countries with limited resources.

PMID- 10916652
TI  - [Optimal myocardial revascularization by coronary bypass and complementary
      angioplasty. Study of 100 patients].
AB  - One hundred patients underwent early coronary angiography (average 20.5 days)
      after coronary bypass surgery between 1994 and 1996. The indications in
      clinically asymptomatic patients were: study of double mammary grafts, non
      respect of the preoperative plan (grafts not available, technical difficulties),
      and/or postoperative ECG changes. 12.1% of internal mammary grafts and 18.2% of
      the saphenous vein grafts were considered to be non-fractional: due to occlusion
      in 3 and 11.9%, due to poor implantation site (persistence of a distal stenosis):
      3 and 0.8% respectively. After investigations to detect ischaemia in the region
      concerned or persistence of a critical lesion on a non-revascularised main
      artery, 26 complementary angioplasties were performed: 3 on internal mammary
      grafts, 4 on saphenous vein grafts and 19 on the native vessels. Surgery alone
      resulted in complete revascularisation in 70% and its association with
      cardiological interventional techniques increased the value to 85%. The
      association of coronary bypass surgery and transluminal angioplasty may therefore
      result in optimal revascularisation. This should reduce the morbidity rate, the
      number of hospital admissions (recurrent ischaemia and reoperation) and improve
      survival. However, the exact modalities of this combined revascularisation remain
      to be defined.

PMID- 10916653
TI  - [Long-term hemodynamic function of the transplanted heart].
AB  - The aim of this study was to identify the long-term haemodynamic changes of the
      transplanted heart. Between 1987 and 1997, 136 patients required cardiac
      transplantation at Dijon hospital. During follow-up, 76 patients aged 51.2 +/-
      9.46 years underwent catheter studies (12 women, 15.8%; and 64 men, 84.2%). Right
      and left heart catheterisation was performed at 3 months, 1, 2, 3 and 5 years
      after transplantation. Right heart catheterisation included measurement of mean
      pulmonary artery and pulmonary capillary pressures and pulmonary arteriolar
      resistances. During left heart catheterisation, cardiac output, mean aortic
      pressure, the ejection fraction, the dp/dt max of the left ventricular wall,
      systemic arterial resistances and left ventricular end diastolic pressures were
      measured. At each catheter study, the indexed myocardial mass, indexed end
      systolic and end diastolic left ventricular volumes, the mass/volume ratio, the
      residual serum cyclosporine concentrations and the serum creatinine were
      analysed. In addition, an endomyocardial biopsy was also performed. Initially
      raised, the mean pulmonary artery and pulmonary capillary pressures decrease from
      the 3rd month to the 2nd year. From the 3rd year onwards, they readjust to the
      upper limits of normal. The pulmonary artery resistances underwent the same
      changes. The left heart parameters remained constant over the period of follow-up
      but with a heart rate, mean aortic pressure and left ventricular end diastolic
      pressure higher than normal. The indexed myocardial mass was increased at all
      periods. The indexed left ventricular end systolic and diastolic volumes
      decreased with a M/V ratio which increased. Cyclosporine concentrations decreased
      whereas serum creatinine increased. The frequency of severe rejection and of
      coronary atherosclerosis was low. Significant correlations were observed between
      different parameters at different periods. In the long-term, the function of the
      transplanted heart is not normal in the strict sense of the term. The apparent
      normality is obtained by anti-hypertensive treatment. The transplanted heart
      adapts to the increase in cyclosporine-induced afterload by permanent myocardial
      hypertrophy, and increased diastolic pressure probably relates to diastolic
      dysfunction without noticeable intracardiac fibrosis.

PMID- 10916654
TI  - [Diagnostic value of stress echocardiography under dobutamine and myocardial
      scintigraphy for restenosis at 6 months after angioplasty of the left anterior
      descending artery].
AB  - This study compared prospectively the diagnostic value of dobutamine
      echocardiography and exercise myocardial scintigraphy for restenosis at 6 months
      after angioplasty of the left anterior descending artery. Forty-one patients aged
      58 +/- 10 years, admitted to hospital for myocardium infarction (N = 22) or
      unstable angina (N = 19), with single vessel disease, were treated by angioplasty
      of one lesion of the left anterior descending artery after initial evaluation of
      the left ventricular ejection fraction by echocardiography. At 6 months, left
      ventricular function was reassessed by echocardiography, dobutamine
      echocardiography and exercise myocardial scintigraphy (Thallium 201) performed
      without treatment. Coronary angiography was performed at the same time and showed
      8 restenosis (19.5%). Overall, in this series, dobutamine echo and scintigraphy
      had respectively a sensitivity of 37.5% and 75%, and a specificity of 97% and 70%
      (p < 0.02). Nine patients had left ventricular dysfunction unchanged compared
      with the initial measurement without viability in the territory of the left
      anterior descending artery with low dose dobutamine (group 1); thirty-two
      patients had improved or normal left ventricular ejection fraction with
      myocardial viability (group 2). In group 1, no cases of restenosis were detected
      by dobutamine echocardiography but_of them had myocardial scintigraphic evidence
      of ischaemia. In group 2, the sensitivity of the two techniques was comparable
      but dobutamine echo was more specific than scintigraphy (96 versus 75%, p =
      0.03). In conclusion, dobutamine echocardiography may be indicated in the
      diagnosis of restenosis of the left anterior descending artery and in cases of
      viability in its territory. In its absence, myocardial scintigraphy seems to be
      preferable.

PMID- 10916655
TI  - [Reference values of intima-medial thickness of carotid and femoral arteries in
      subjects aged 20 to 60 years and without cardiovascular risk factors].
AB  - Many studies have shown a close correlation between intima-medial thickness of
      the carotid artery measured by high resolution ultrasonography and the presence
      of coronary artery disease or atherogenic risk factors. However, reference values
      for the value of intima-medial thickness (IMT) in healthy subjects have not yet
      been established. The aim of this study was, therefore, to determine the
      reference values of carotid (C-IMT) and femoral intima-medial thickness (F-IMT)
      with respect to age and gender in healthy subjects (53 women and 45 men) aged 20
      to 60, with no family or personal history of cardiovascular disease or
      atherogenic risk factors, underwent high resolution colour echo-Doppler
      examination. The mean C-IMT was 556 +/- 57 microns in women and 573 +/- 70
      microns in men (NS), and the femoral equivalent was 543 +/- 63 microns in women
      and 562 +/- 74 microns in men (NS). Between the ages of 20 and 60, the C-IMT
      increased by 1.8 microns per year (p < 0.03) in women and 3.4 microns (p < 0.001)
      in men, the variations being respectively 1.2 microns (NS) and 3.1 microns (p <
      0.002) in the femoral artery. Multiple regression analysis including gender and
      individual values of age, body mass index and lipid profile confirmed that only
      age was significantly correlated to the increase in thickness. The authors
      conclude that the reference values of IMT do not differ with gender or site of
      analysis, but there is a slight influence with respect to age.

PMID- 10916656
TI  - [Cardiac fibroelastoma. Six operated cases and review of the literature].
AB  - The authors reviewed the cases of 6 patients operated between September 1994 and
      February 1999 for a rare benign tumour: papillary fibroelastoma of the heart.
      These patients, aged 51 +/- 14 years, all have single valvular involvement:
      mitral (N = 3), aortic (N = 2), tricuspid (N = 1). Five patients were
      symptomatic: transient ischaemic cerebral events (N = 3) associated with
      mesenteric infarction requiring ileal resection in 1 case; constituted
      cerebrovascular accident (N = 1); syncope (N = 1). In this last patient, the
      fibroelastoma was diagnosed fortuitously on the tricuspid valve. The features and
      location of the tumours were determined by transoesophageal echocardiography.
      Surgical treatment in all patients consisted in excising the tumour and
      preserving the valve. One aortic cusp was reconstructed after excising the tumour
      with a cryopreserved partial aortic homograft. Peroperative transoesophageal
      echocardiography confirmed the absence of regurgitation after the procedures in
      all patients. There were no postoperative complications in any of the cases. No
      cases of valvular regurgitation or of tumour recurrence were observed during
      follow-up. Despite the benign histology, cardiac fibroelastomas should be excised
      because of their embolic complications. Absence of recurrence justifies
      conservative reconstruction of the affected valve.

PMID- 10916657
TI  - [Cartography of absolute myocardial perfusion with magnetic resonance imaging.
      Methods and results].
AB  - Ultra-rapid dynamic MRI (one image per heart beat) can follow the progression of
      the intra-myocardial signal during the first passage of diffusable gadolinium
      chelates injected as a bolus through a peripheral vein. A quantitative evaluation
      of myocardial perfusion is possible using a compartmental model of analysis.
      Absolute myocardial flow can be measured at rest and during hyperaemia induced by
      dipyridamole. It is possible to associate functional mapping, corresponding to
      parametric images of the flow indices, to the global evaluation. The ratio
      between the values obtained during hyperaemia and under basal conditions
      correspond to the myocardial reserve. The principles, results and limitations of
      this method are discussed in the light of published results, underlining the
      advantages of absolute flow measurement and of the differences between the
      results of MRI and myocardial scintigraphy.

PMID- 10916658
TI  - [Ventricular tachycardia by branch to branch re-entry. Familial case with
      Steinert's disease].
AB  - Ventricular tachycardia by branch to branch reentry is a rare arrhythmia. It
      occurs in cardiomyopathies associated with conduction defects. During tachycardia
      a His potential precedes each QRS complex which usually has a left bundle branch
      block appearance. The authors report two familial cases of ventricular branch to
      branch tachycardia (son and mother) without cardiomyopathy. The diagnosis of
      Steinert's disease was made post-mortem in these two patients. In cases of branch
      to branch ventricular tachycardia, the diagnosis of myotonic dystrophy should be
      excluded. Conversely, endocavitary electrophysiological investigation with
      ventricular stimulation should be proposed for symptomatic patients (dizzy
      spells, syncope) to diagnose branch to branch ventricular tachycardia, even in
      cases with conduction defects which could also explain the symptoms.

PMID- 10916659
TI  - [Left ventricular thrombus revealed by electron bean computed tomography, in a
      patient with antiphospholipid syndrome].
AB  - The authors report a case of a 48 year old woman admitted to hospital because of
      digital ischemia, in a context of antiphospholipid syndrome. The
      electrocardiogram-triggered electron beam computed tomography revealed an apical
      thrombus associated with a thinning left ventricular wall, suggesting painless
      myocardial infarction. The diagnosis was secondary confirmed by coronarography.

PMID- 10916660
TI  - [Pathologic anatomy and cardiology].

PMID- 10916661
TI  - [How can we improve the management of respiratory medicine services?].

PMID- 10916662
TI  - [Inhalation technique in patients with chronic respiratory diseases].
AB  - OBJECTIVE: To determine how inhalers are used by patients with chronic
      respiratory diseases in the Community of Valencia (Spain) and to identify the
      factors associated with correct use. MATERIAL AND METHODS: We carried out a
      prospective study of 554 patients (331 men, 223 women, mean age 50.5 +/- 21.5
      years) who underwent spirometric testing (292 with bronchial asthma, 192 with
      COPD, 15 with bronchiectasis and 55 with other diagnoses). The patients were
      asked what type of inhaler they used. Pressurised canisters (PC) were used by
      39.9%, inhalation chambers (IC) by 37.9% and dry powder inhalers (Turbuhalers)
      (DP) by 22.2%. They were also asked what instructions they had received; the
      inhalation techniques recommended by the Spanish Society of Pneumologists and
      Chest Surgeons (SEPAR) was reviewed step by step. RESULTS: a) Four hundred thirty
      two patients (78%) reported having received instruction in how to use the
      inhaler; b) One hundred seventy-five (31.6%) used the correct technique: 25.3%
      using PC, 32.4% using IC and 41.5% using DP (p = 0.008); c) The most common
      errors were not holding the breath after inhaling in the case of PC users, not
      waiting 30 seconds between inhalation maneuvers and the lack of synchrony with
      inspiration among PC users; d) Use of correct inhalation technique was associated
      with prior instruction (rs = 0.249; p < 0.001) and younger age (rs = 0.92; p =
      0.03). CONCLUSIONS: A high percentage of patients, particularly those using PC
      and those who received no instruction, use inhalers incorrectly in the Community
      of Valencia. We therefore recommend health education programs that target the
      main errors identified.

PMID- 10916663
TI  - [Prevalence of and attitudes towards smoking in a population over 40 years of
      age].
AB  - OBJECTIVES: Smoking is the main cause of preventable death in developed
      countries. One of the most relevant health care interventions is convincing
      smokers to quit. To achieve that end, it is important to know, in addition to the
      prevalence of smoking, the degree of physical addiction to nicotine and smokers'
      attitudes toward tobacco. MATERIAL AND METHODS: This study collects results from
      a Spanish national epidemiological study (the IBERPOC study) related to smoking
      addiction, smokers' degree of addiction to nicotine and smokers attitudes toward
      their habits. The data has been obtained by surveying 4,035 individuals selected
      randomly from census data in seven different parts of the country. Information
      was obtained from questionnaires and CO in expired air was measured. RESULTS: One
      thousand fifty-nine respondents were smokers (26%) and 968 were ex-smokers (24%).
      Female smokers were younger (47 versus 51 years old) and had started smoking
      later (at age 22 versus 17 years), smoked fewer cigarettes per day (15 versus 21)
      and had lower concentrations of CO in expired air (13.4 versus 17 ppm) (p < 0.001
      for all comparisons). Six hundred fifty-nine smokers (62.2%) had tried to quit at
      least once. The most important reasons given for trying to quit were related to
      improving health. CONCLUSIONS: The 26% of the surveyed population smoked. Women
      generally started later, smoked fewer cigarettes and were less physically
      addicted to nicotine. Most smokers had tried at least once to quit, particularly
      if motivated to improve health. These results should be considered when proposing
      strategies for smoking cessation.

PMID- 10916664
TI  - [Surgical treatment of lung cancer: comparative assessment of the staging systems
      of 1986 and 1997. Results in 500 consecutive patients].
AB  - OBJECTIVE: To evaluate the influence of different variables on survival in
      relation to the staging guidelines of 1986 and 1997. PATIENTS AND METHODS: Five
      hundred patients (473 men and 27 women) with non-small cell lung cancer were
      treated surgically from 1980 to 1997. Resections performed: 184 lobectomies, 16
      bi-lobectomies, 244 pneumonectomies, 2 bronchoplastic lobectomies, and 54
      segmentectomies. HISTOLOGY: 338 epidermoid, 86 adenocarcinoma, 40 giant cell, 36
      mixed tumor. Differentiation: 216 N1, 91 N2, 193 N3. Stages according to 1986
      guidelines were I: 246 (49.2%) (T1: 32, T2: 214); II: 27 (5.4%); IIIa: 197
      (39.4%) (N0: 84; N1: 2; N2: 111); IIIb: 23 (4.6%) (N0: 12; N2: 11); and IV: 7
      (1.4%) (N0: 4; N2: 3). Stages according to the 1997 guidelines were used for
      comparison of survival between patients with Ia and Ib tumors and with IIb and
      IIIa tumors. RESULTS: With follow-up periods ranging from 2 to 17 years, 141
      patients (28%) were alive, 26 (5%) were lost to follow-up and 333 had died. Two
      patients (0.4%) died during surgery and 36 (7.2%) died during the postoperative
      period. Among the remaining 462 patients, 295 deaths were related to the
      following causes: metastasis in 130 cases (44%), recurrence in 81 cases (27%),
      functional causes in 17 (6%), independent causes in 54 (18%) and unknown causes
      in 13 (4%). Overall survival rates at 5 and 10 years were 36 and 26%,
      respectively; survival rates by histological type: epidermoid 36 and 26%,
      adenocarcinoma 35 and 26%; stage I, 51 and 41% (Ia, 81 and 75%; Ib, 44 and 33%);
      IIIa 24 and 15% (IIb of 1997: 27 and 17%; IIIa of 1997: 20 and 13%). Survival by
      N factor: N0, 44 and 34%; N2, 17 and 8% (1986) and 17 and 11% (1997).
      CONCLUSIONS: Survival agrees with other studies. The 1997 staging guidelines are
      useful for differentiating survival between stages Ia and Ib and between IIb and
      IIIa. N and T factors, histology and stage influence the appearance of
      metastasis; T factor influences recurrence.

PMID- 10916665
TI  - [Perioperative morbimortality in pneumonectomy. Analysis of risk factors].
AB  - Pneumonectomy continues to be associated with high rates of morbidity and
      mortality. OBJECTIVE: The aim of this study was to determine the mortality and
      morbidity rates after pneumonectomy and to analyze perioperative risk factors
      related to mortality. PATIENTS AND METHODS: The cases of 266 patients undergoing
      pneumonectomy between January 1986 and December 1997 were reviewed
      retrospectively: 241 patients with lung cancer, 4 with pulmonary metastasis, 9
      with bronchiectasis and 12 with other benign diseases; 13% received neoadjuvant
      therapy. The bronchial stump was stapled in 92%, sutured in 8%, and covered with
      autologous tissue in 73%. Intrapericardial pneumonectomy was performed in 32%,
      pneumonectomy extended to the chest wall or diaphragm in 9%, and completion
      pneumonectomy was performed in 3%. We collected general demographic data, medical
      histories, pulmonary function data and surgical technique. Deaths and
      postoperative complications within the first 30 days after pneumonectomy were
      also known. RESULTS: Two hundred sixty-six pneumonectomies were performed [right
      102 (38%); left 164 (62%)] in 249 men (93%) and 17 women (7%) who were 58 +/- 11
      years of age (20 to 79 years). The rate of early postoperative death (30 days)
      was 5.6%. Mortality rates were higher among patients over 70 years of age (p =
      0.045), diabetics (p = 0.038), patients undergoing neoadjuvant therapy (p =
      0.031), those with FEV1 under 1,800 ml (p = 0.013), cases of right-sided
      pneumonectomy (p = 0.001), cases of extended pneumonectomy (p = 0.037) or those
      without coverage of the bronchial stump (p = 0.005). Mortality was also higher
      when complications appeared involving the bronchial stump (p < 0.01), heart (p <
      0.001), respiration (p < 0.001) or digestion (p = 0.002). Overall morbidity was
      40%. Surgical complications developed in 23%: postpneumonectomy empyema (10%),
      bronchopleural fistula (7%) (with no significant difference related to stapling
      or suturing), hemothorax (3%) and wound complications (3%). Twelve patients
      (4.5%) underwent second operations. Cardiac morbidity was 20% (atrial
      fibrillation in 12%), respiratory morbidity was 8% and other complications
      appeared in 19% of cases. CONCLUSION: In our experience, mortality after
      pneumonectomy is 5.6% with an overall complication rate of 40%, mainly due to
      surgical and cardiac complications. Coverage of the bronchial stump with
      autologous tissue reduces the risk of postoperative death due to fistula and/or
      empyema after pneumonectomy.

PMID- 10916666
TI  - [Standards for respiratory rehabilitation. Task Force of the SEPAR].

PMID- 10916667
TI  - [Function of respiratory muscles in COPD].

PMID- 10916668
TI  - [Treatment with Bi-PAP in patients with bilateral diaphragm paralysis].
AB  - Two patients with bilateral diaphragmatic paralysis are described. The first case
      occurred secondary to open chest surgery; the second occurred in a
      polytraumatized patient. Both were successfully treated with intermittent bi
      level positive airway pressure (Bi-PAP). Bilateral diaphragmatic paralysis can be
      related to a variety of processes, although idiopathic forms also occur.
      Diagnosis can be difficult and should involve a high level of clinical suspicion.
      Treatment and prognosis are determined by the underlying disease. Some cases may
      require the establishment of nighttime support ventilation. Techniques for non
      invasive ventilatory assistance such as Bi-PAP can improve symptoms markedly and
      allow patients to live independently.

PMID- 10916669
TI  - [Treatment of tracheal stenosis with a new self-expanding metal prosthesis with
      "shape memory"].

PMID- 10916670
TI  - ["Selected" specialists].

PMID- 10916671
TI  - [Alveolar proteinosis. Treatment with total lung lavage].

PMID- 10916672
TI  - [Initial response to steroids of lung non-Hodgkin's lymphoma].

PMID- 10916673
TI  - [Late metastasis of osteosarcoma].

PMID- 10916674
TI  - [Recurrent hemoptysis secondary to tracheal glomus tumor].

PMID- 10916675
TI  - Biochemical and genetic basis of red cell enzyme deficiencies.
AB  - Enzyme deficiencies have been identified in all erythrocyte pathways. Their
      frequencies differ with respect to the affected enzyme, the severity of the
      clinical manifestations and the geographical distribution. Most mutations are
      found within the coding sequences of genes, missense mutations occurring more
      often than deletions, insertions, splice site defects or premature stop codons.
      Promoter mutations are rare. The clinical manifestations are chronic or non
      chronic haemolytic anaemias. The first of these are characterized by an
      impairment of cell function at normal values of the external load parameters
      kATPase and kGSHox. Haemolysis with a non-chronic course is induced only at
      enhanced values of the load parameters, caused by free radical generation by
      oxidative drugs, fava beans, infections, fever and physical exercise. The
      development of secondary haemochromatosis is the most common cause of mortality
      in patients suffering from severe chronic non-spherocytic haemolytic anaemia.
      Intracellular iron deposits must be prevented by timely treatment with effective
      chelating agents.

PMID- 10916676
TI  - Glucose-6-phosphate dehydrogenase deficiency.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) is expressed in all tissues, where it
      catalyses the first step in the pentose phosphate pathway. G6PD deficiency is
      prevalent throughout tropical and subtropical regions of the world because of the
      protection it affords during malaria infection. Although most affected
      individuals are asymptomatic, there is a risk of neonatal jaundice and acute
      haemolytic anaemia, triggered by infection and the ingestion of certain drugs and
      broad beans (favism). A rare but more severe form of G6PD deficiency is found
      throughout the world and is associated with chronic non-spherocytic haemolytic
      anaemia. Many deficient variants of G6PD have been described. DNA sequence
      analysis has shown that the vast majority of these are caused by single amino
      acid substitutions. The three-dimensional structure of G6PD shows a classical
      dinucleotide binding domain and a novel beta + alpha domain involved in
      dimerization.

PMID- 10916677
TI  - Chronic non-spherocytic haemolytic disorders associated with glucose-6-phosphate
      dehydrogenase variants.
AB  - Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human
      enzyme defect, being present in over 400 million people world wide. In a small
      number of cases, G6PD deficiency can lead to mild-to-severe chronic haemolysis,
      which is further exacerbated by oxidative stress. Such G6PD variants have been
      described all over the world and are responsible for chronic non-spherocytic
      haemolytic anaemia (CNSHA). To date 61 G6PD molecular variants associated with
      CNSHA have been identified, only some of which can cause the severe reduction in
      stability of the red blood cell enzyme. The distribution of the different
      mutations shows a predominance of small mutational events, and many have been
      found repeatedly in different parts of the world. By revisiting the 61 class I
      variants described so far, we can observe that a low inhibition constant (Ki) for
      NADPH, a higher Km for substrates and a reduced thermostability are common.

PMID- 10916678
TI  - Red cell pyruvate kinase deficiency: from genetics to clinical manifestations.
AB  - Pyruvate kinase deficiency is the most frequent enzyme abnormality of the Embden
      Meyerhof pathway causing hereditary non-spherocytic haemolytic anaemia. The
      degree of haemolysis varies widely, ranging from very mild or fully compensated
      forms, to life-threatening neonatal anaemia and jaundice necessitating exchange
      transfusions. Splenectomy should be reserved for young patients who require
      regular blood transfusions. The gene encoding for pyruvate kinase (PK-LR) has
      been localized to the long arm of chromosome I; the cDNA of R-type is 2060 bp
      long and codes for 574 amino acids. More than 130 different mutations, mostly
      missense, have so far been described in association with PK deficiency, 1529A and
      1456T being considered to be the most common mutations in Caucasians. Analysis of
      the three-dimensional structure of the enzyme may help in predicting the severity
      of the molecular defect. Further data on clinical features of homozygous patients
      are needed, at least for some mutations, to allow a more precise
      genotype/phenotype correlation.

PMID- 10916679
TI  - Hexokinase: gene structure and mutations.
AB  - Hexokinase (HK) deficiency is a rare red cell enzyme deficiency associated with
      hereditary non-spherocytic haemolytic anaemia; to date, only 17 affected families
      have been reported. Human HK has four major isozymes, each of which is encoded by
      a separate gene. Recent studies have shown that both ubiquitously expressed type
      I HK (HK-I) and erythroid-specific HK-R are expressed in erythrocytes, and that
      these isozymes are encoded by the single HK-I gene. The human HK-I gene has 19
      exons, the HK-I and HK-R transcripts being produced by using two distinct
      promoters. Thus, the first and second exons are specifically utilized for the
      erythroid-specific HK-R and ubiquitously expressed HK-I isozymes respectively. So
      far, only two HK variants have been analysed at the molecular level. Since the
      human HK-I crystal structure has recently been elucidated, the molecular analysis
      of the HK variants will be useful for discussing the structure-function
      relationship of the enzyme.

PMID- 10916680
TI  - Glucose-6-phosphate isomerase deficiency.
AB  - Most of the metabolic needs of erythrocytes are covered by glycolysis, the
      oxidative pentose phosphate pathway and the glutathione cycle. Hereditary enzyme
      deficiencies of all these pathways have been identified, among which glucose-6
      phosphate isomerase (GPI) deficiency is the second most frequent
      erythroenzymopathy in glycolysis, being associated with non-spherocytic
      haemolytic anaemia of variable severity. This autosomal recessive genetic
      disorder may be associated in some cases with neurological impairment. GPI is a
      dimeric enzyme that catalyses the reversible interconversion of fructose-6
      phosphate and glucose-6-phosphate. Virtually all the mutant gene products
      reported are characterized by marked instability and normal substrate affinities,
      but altered catalytic activity and electrophoretic migration rates. At the
      nucleotide level, 29 mutations have been reported. This chapter reviews (a) the
      clinical pattern of the condition; (b) biochemical and molecular studies; (c)
      structure-function relationships; (d) the molecular basis of neurological
      dysfunctions sometimes associated with GPI deficiency; and (e) the correlation
      between the severity of the anaemia and the molecular defect.

PMID- 10916681
TI  - Chronic non-spherocytic haemolytic anaemia due to congenital pyrimidine 5'
      nucleotidase deficiency: 25 years later.
AB  - In 1972, Valentine et al described, under the name of 'non-spherocytic haemolytic
      anaemia, high red cell ATP and ribose phosphate pyrophosphokinase (RPK; EC
      2.7.6.1) deficiency', an obscure congenital haemolytic anaemia with the
      characteristic feature of red blood cell basophilic stippling. The activity of
      Embden-Meyerhof pathway and hexose monophosphate shunt were normal, and the
      concentrations of reduced glutathione and of ATP were raised 2 SD above the
      normal mean. The low values of RPK also encountered were considered to be an
      epiphenomenon rather than a causative defect. One year later, further studies
      performed in two new kindreds with the same haemolytic disorder associated with
      persistent basophilic stippling were described under the name of 'haemolytic
      disorders associated with increased ATP'. In 1974, two new and important
      observations contributed to the final identification of the disease: the
      patients' red blood cells (RBCs) contained large amounts of nucleotides
      (pyrimidine nucleotides), and in all cases they were deficient in a hitherto
      unrecognized enzyme called pyrimidine 5' nucleotidase (P5N). In conclusion, all
      these cases were formerly referred to as 'high ATP syndromes' because of the
      erroneous assumption that the large number of nucleotides within deficient RBCs
      were adenine phosphate rather than pyrimidine phosphate. Twenty-five years after
      its description, P5N deficiency has been reported in about 35 unrelated families
      from different parts of the world, and it has become one commonly identified
      cause of hereditary non-spherocytic haemolytic anaemia due to RBC enzymopathy.
      Genetic transmission is via the autosomic recessive mode, and only homozygous or
      compound heterozygous are clinically affected. Family members who are
      biochemically heterozygous are haematologically normal and difficult to detect.
      Unfortunately, the precise gene mutation or mutations causing the disease remain
      unknown.

PMID- 10916682
TI  - Triosephosphate isomerase deficiency: historical perspectives and molecular
      aspects.
AB  - In this chapter, the original descriptions and pre-molecular studies of
      triosephosphate isomerase (TPI) deficiency are summarized, and the molecular
      aspects of the disease presented. The gene is well characterized, and several
      mutations have been described. Structure-function studies have led to an
      increased understanding of impaired catalysis. All kindreds that have been
      studied with the predominant Glu104Asp mutation are linked by a common haplotype,
      indicating descent from a common ancestor. Variant upstream substitutions occur
      in high frequency in persons of African and East Asian lineage and in lower
      frequency in other groups, but the possible role, if any, of these variants in
      clinical TPI deficiency requires further investigation. The possible contribution
      of deviant lipid metabolism to the pathogenesis of the disorder has been
      extensively investigated, and an intriguing new area of inquiry is the apparent
      cell-to-cell transfer of enzyme in cell culture systems, raising the question of
      the feasibility of enzyme or gene replacement therapy.

PMID- 10916684
TI  - Penetrating injury from horseshoe crab tail.

PMID- 10916683
TI  - Other erythrocyte enzyme deficiencies associated with non-haematological
      symptoms: phosphoglycerate kinase and phosphofructokinase deficiency.
AB  - Phosphoglycerate kinase (PGK) deficiency is associated with hereditary haemolytic
      anaemia and often with central nervous system dysfunction and/or myopathy. Twenty
      three families have been discovered with this condition. Nine have manifested
      both symptoms, six only haemolysis, and seven central nervous system dysfunction
      and/or myopathy without haemolysis; one case is asymptomatic. Among them, the
      structural abnormalities of 14 mutants, including 11 missense mutations, 1 gene
      deletion, 1 gene insertion, and 1 splicing mutation, have been identified. The
      correlation between the phenotypic and structural differences in PGK deficiency
      remains to be defined. Splenectomy obviates transfusion in most patients but does
      not correct the haemolytic disorder. Phosphofructokinase (PFK) deficiency is
      associated with myopathy and/or haemolysis. More than half reported had the
      typical features of glycogen storage disease type VII (Tarui disease). The other
      cases exhibited myopathy alone, haemolytic anaemia alone, or no clinical symptom
      at all. Eight missense, 1 nonsense, 1 frameshift and 5 splicing mutations have
      been determined in the PFK-M gene. In classic PFK-M deficiency, the avoidance of
      undue exertion is the key to prevent muscle symptoms.

PMID- 10916685
TI  - Palatal necrosis in an AIDS patient: a case of mucormycosis.
AB  - We report a case of rhinocerebral mucormycosis presenting in a patient with AIDS
      and review the literature on mucormycosis occurring in the setting of HIV
      disease. Mucormycosis in HIV is rare. However, it can be the presenting
      opportunistic infection in AIDS. Predisposing factors for Mucor infection in HIV
      disease include low CD4 count, neutropenia, and active intravenous drug use.
      Mucormycosis can present in the basal ganglia, the skin, the gastrointestinal
      tract, the respiratory tract, or may be disseminated. The disease may develop
      insidiously or may progress rapidly with a fulminant course. Therapy usually
      consists of surgical debridement/excision accompanied by intravenous amphotericin
      B.

PMID- 10916686
TI  - Cafe-au-lait spots.

PMID- 10916687
TI  - Psychotropic agent-induced black hairy tongue.
AB  - Black hairy tongue is characterized by an abnormal coating of the dorsal surface
      of the tongue. Although the cause is unknown, several precipitating factors may
      be implicated in the pathogenesis of this disorder. A case is presented in which
      black hairy tongue appeared subsequent to the administration of fluoxetine
      hydrochloride, thiothixene hydrochloride, benztropine mesylate, and clonazepam
      for bipolar affective disorder.

PMID- 10916688
TI  - Fixed drug eruptions to human immunodeficiency virus-1 protease inhibitor.
AB  - Despite numerous drug interactions that occur with human immunodeficiency virus-1
      protease inhibitors, there are relatively few drug reactions. We present two
      patients receiving saquinavir who developed fixed drug reactions. Both reactions
      cleared while patients received a therapeutic dose of the medication, and in one
      patient a flare was seen when the patient later stopped and then restarted the
      medication. Although fixed drug reactions are relatively inconsequential, it is
      important to know that these eruptions may clear when the patient is given
      uninterrupted therapy of a human immunodeficiency virus-1 protease inhibitor,
      with only post-inflammatory hyperpigmentation.

PMID- 10916689
TI  - Nevoid basal cell carcinoma syndrome and non-Hodgkin's lymphoma.
AB  - Nevoid basal cell carcinoma syndrome (NBCCS) is a hereditary disorder with a
      predilection for numerous basal cell carcinomas in addition to odontogenic
      keratocysts, palmoplantar pitting, and skeletal malformations. NBCCS has been
      associated with a number of benign and malignant neoplasms. We report the first
      case of NBCCS in association with non-Hodgkin's lymphoma.

PMID- 10916690
TI  - Scurvy in an unrepentant carnivore.
AB  - For centuries, scurvy, or vitamin C deficiency, decimated crews of sailing ships
      on long sea voyages and populations deprived of fresh fruits and vegetables
      during times of war or famine. Today, scurvy is extremely rare in the United
      States, and its classic findings of perifollicular petechiae, edema and purpura
      of the lower extremities, corkscrew hairs, and hemorrhagic gingivitis may go
      unrecognized. We report the case of a man from rural Appalachia who developed
      typical signs and symptoms of scurvy on two separate occasions, approximately 2
      years apart. Both times, the patient underwent an extensive work-up and was
      diagnosed with numerous other conditions before his vitamin C deficiency was
      recognized. We discuss the clinical presentation, pathophysiology, diagnosis, and
      treatment of scurvy, with attention to specific findings that should alert the
      clinician to this diagnosis.

PMID- 10916691
TI  - Treatment of chromoblastomycosis due to Fonsecaea pedrosoi with low-dose
      terbinafine.
AB  - Chromoblastomycosis, or chromomycosis, is a chronic fungal infection of the skin
      and subcutaneous tissues caused by a species of dematiaceous fungi. We present a
      patient with chromoblastomycosis due to Fonsecaea pedrosoi, who was treated with
      8 months of terbinafine 250 mg by mouth daily with histologic and mycologic cure.

PMID- 10916692
TI  - Calciphylaxis.
AB  - Calciphylaxis is a rare, life-threatening condition of widespread metastatic
      calcification most commonly seen in the setting of end-stage renal disease. The
      etiology of calciphylaxis is not well described, though there are several
      hypotheses. Cutaneous lesions are characteristically found on the abdomen,
      buttocks, or thighs as reticulated, painful, purple plaques that often undergo
      ulceration and may serve as a portal of entry for potentially life-threatening
      infectious agents. Histology reveals medial calcification with intimal
      proliferation involving small vessels in the subcutaneous fat, associated with a
      lymphohistiocytic infiltrate of the affected lobules. Treatment, including
      phosphate binders and parathyroidectomy, is not universally effective. We present
      one case of calciphylaxis and discuss the clinical features, pathophysiology,
      histology, and treatment of the condition.

PMID- 10916693
TI  - Clinical management of the acute sunburn reaction.
AB  - Critical reviews of published human studies about pharmacologic agents used to
      treat the sunburn reaction show that systemic and topical corticosteroids have
      little or no clinically important effect on the sunburn reaction. Systemic and
      topical nonsteroidal anti-inflammatory drugs, when used at dosages to achieve
      optimal serum levels for anti-inflammatory effect, only result in an early and
      mild reduction of ultraviolet B-induced erythema. Due to the lack of demonstrated
      clinical efficacy of these and other medicines to eliminate sunburn or decrease
      healing time, we currently suggest conservative local symptomatic treatment with
      adequate pain control until the sunburn naturally resolves.

PMID- 10916694
TI  - Case report: teledermatology and epiluminescence microscopy for the diagnosis of
      scabies.
AB  - We wish to share images from a patient seen in our teledermatology program. Due
      to the absence of on-site dermatology services at the Togus, Maine, Department of
      Veterans Affairs, and associated community clinics for veterans in Aroostook,
      Bangor, Calais, and Rumford, we created a program to provide dermatologic
      expertise from Providence, Rhode Island. Patients referred for this service were
      evaluated by a nurse practitioner, who obtained a history, performed a physical
      examination, and captured digital images of the affected area of skin, including
      epiluminescence microscopic images where indicated. These data were then
      retrieved at the Providence (host) site and reviewed by a dermatologist, who
      formulated an impression and plan that was then implemented by the remote site in
      Maine. This approach, which involves image capture at the remote site and later
      review of images at the host site, is the "store-and-forward" method, which
      appears to be a relatively cost-effective means of providing this service from a
      distance.

PMID- 10916695
TI  - Epidermolysis bullosa acquisita associated with relapsing polychondritis: an
      association with eosinophilia?
AB  - Epidermolysis bullosa acquisita is a blistering disorder that has been associated
      with other autoimmune diseases. It has not previously been associated with
      relapsing polychondritis (RPC). RPC is an autoimmune disorder that frequently
      displays peripheral eosinophilia. The eosinophil has been implicated in mediation
      of tissue damage and bullae formation. RPC should be added to the list of
      diseases seen in association with EBA.

PMID- 10916696
TI  - What is your diagnosis? Nail-patella syndrome.

PMID- 10916697
TI  - Addison's disease: the potentially life-threatening tan.
AB  - Addison's disease is a potentially life-threatening endocrine disorder. The
      classic dermatologic sign of Addison's disease is diffuse hyperpigmentation of
      the skin with focal hyperpigmentation of scars, nails, and the oral mucosa.
      Recognition of these dermatologic manifestations in a patient with otherwise
      vague constitutional symptoms warrants a consideration of Addison's disease.

PMID- 10916698
TI  - Treatment of trichostasis spinulosa with a hydroactive adhesive pad.
AB  - Trichostasis spinulosa is a common skin condition that may be easier to diagnose
      than to treat. Successful treatment with the use of a hydroactive adhesive "deep
      cleaning" pad (Biore) is discussed.

PMID- 10916699
TI  - Papular elastosis.
AB  - I report two typical cases of a cutaneous disorder caused by sunlight, which is
      common in Phoenix, Arizona, "The Valley of the Sun." It currently masquerades
      under the misnomer, adult colloid milium. It generally presents clinically as
      asymptomatic, shiny, smooth, firm papules, 1 to 10 mm in diameter, involving
      chronically sun-damaged skin of adults. The papules are generally multiple, but
      may be solitary, with various colorations. Microscopically, the papules all show
      severe elastosis involving most of the papillary cutis. It is most important to
      biopsy these lesions because clinically they may mimic a variety of skin lesions,
      some of which would require further investigations and therapy. This is a
      distinct clinical form of severe solar elastosis, which I propose to term papular
      elastosis.

PMID- 10916700
TI  - Muscle and tendon contributions to force, work, and elastic energy savings: a
      comparative perspective.
AB  - Muscle-tendon architecture underlies muscle function. Whereas muscles generally
      contribute most to mechanical work, tendons provide the majority of elastic
      energy savings. Isometric or eccentric contractions enhance force and further
      reduce energy cost. However, elastic savings is probably constrained by the need
      to reduce compliance for accurate control of position.

PMID- 10916701
TI  - Female reproductive hormones and thermoregulatory control of skin blood flow.
AB  - Changes in progesterone and estrogen levels over the course of the menstrual
      cycle, with oral contraceptives or with hormone replacement therapy alter
      thermoregulatory control of skin blood flow and body temperature at rest and
      during exercise. We review here recent evidence concerning the sites and
      potential mechanisms of these influences.

PMID- 10916702
TI  - AMP-activated protein kinase: a critical signaling intermediary for exercise
      stimulated glucose transport?
AB  - Physical exercise increases the rate of glucose transport into contracting
      skeletal muscles by a mechanism that involves translocation of the GLUT4 glucose
      transporter to the cell surface. This brief report will discuss an emerging
      hypothesis that suggests that the AMP-activated protein kinase is a key signaling
      intermediary leading to exercise-stimulated GLUT4 translocation in skeletal
      muscle.

PMID- 10916703
TI  - Applications of microdialysis in studies of exercise.
AB  - Microdialysis provides a means of determining nutrient blood flow as well as
      continuous simultaneous determination of the interstitial concentration of
      nutrients and metabolites. Microdialysis also allows for local delivery of
      pharmacological agents to tissue without resultant systemic effects. The
      potential of microdialysis for exercise studies is clear, yet relatively
      untapped.

PMID- 10916704
TI  - Near-infrared spectroscopy: what can it tell us about oxygen saturation in
      skeletal muscle?
AB  - Near-infrared spectroscopy (NIRS) measures hemoglobin saturation in small
      vessels. A number of interesting studies have used this method. However,
      difficulties with signal quantification and studies in which NIRS oxygen
      saturation did not behave as expected raise concerns. NIRS remains promising for
      studies of skeletal muscle, but a better understanding of the method is needed.

PMID- 10916705
TI  - Exercise, stress, and the immune conversation.
AB  - The role of exercise in meaningful alterations in immune function is unclear. The
      recent demonstration that stress proteins are potent modulators of immune cell
      activation and cytokine production, coupled with the role of exercise in stress
      protein production, suggest that exercise-associated alterations in immune
      function may be related to exercise associated alterations in the cellular stress
      response.

PMID- 10916706
TI  - Exercise hyperpnea: where do we go from here?
AB  - Pulmonary ventilation (VE) increases during exercise to meet the demands of
      increased oxygen consumption (VO2) and CO2 production. Despite numerous studies
      over the past century, the mechanism mediating exercise hyperpnea remains
      controversial. Progress has been limited primarily by the incomplete
      understanding of the complex basic ventilatory control system and by the
      difficulty of significantly manipulating a single potential pathway while still
      performing physiologic exercise. Where do we go from here to further study the
      exercise hyperpnea?

PMID- 10916707
TI  - Muscular force or work: what determines the metabolic energy cost of running?
AB  - It has been proposed that the metabolic energy cost of running is determined by
      the magnitude and rate of muscular force generation needed to oppose gravity and
      operate muscle-tendon springs. Whole animal experiments, in vivo muscle force and
      fascicle length recordings, and in vitro muscle shortening velocity data support
      the idea.

PMID- 10916708
TI  - Electronic medical records personified.

PMID- 10916709
TI  - Virtual seminars for medical nutrition education.

PMID- 10916711
TI  - (Whose) family values?: a literary inquiry.

PMID- 10916710
TI  - Demand for family medicine faculty.

PMID- 10916712
TI  - Answering funding preferences for medical school graduates in underserved areas.
AB  - We describe here a feasible and data-based approach for obtaining important
      information about the percentage of our medical school graduates who primarily
      provide health care to the medically underserved. The logic and data used in our
      methodology have been acceptable to funding agencies. After making the initial
      investment in developing this approach, we can execute it at low cost to respond
      to relevant inquiries about the practice activities of our graduates. Other
      programs that can produce a computerized listing of post-residency graduates'
      practice locations can follow the procedure outlined above to demonstrate
      qualification for funding preferences.

PMID- 10916713
TI  - Medical students and Health Care Financing Administration documentation
      guidelines.

PMID- 10916714
TI  - Research at the STFM Annual Spring Conference: current status and future trends.

PMID- 10916715
TI  - Involving all family physicians and family medicine faculty members in the use
      and generation of new knowledge.

PMID- 10916716
TI  - Medical student evaluation of family nurse practitioners as teachers.
AB  - BACKGROUND: Demands on family medicine faculty to generate clinical revenue may
      negatively impact the undergraduate medical education program. To minimize this
      possibility and better model interprofessional education, family nurse
      practitioners (FNPs) were hired as clinicians and teachers as part of a
      longitudinal family medicine clerkship. This paper reports the results of a pilot
      study of student evaluations of nurse practitioner teaching. METHODS: All M3 and
      M4 students were asked to evaluate one of three FNPs who had precepted them
      multiple times during their previous year of ambulatory care practice. Two
      previously studied closed-ended questionnaires were used to assess quality of
      teaching by the FNPs. Students also responded to a series of open-ended
      questions. RESULTS: Ninety-one percent of 97 students responded to the survey.
      Responses to the closed-ended questions as well as comments by the students and
      physicians were positive regarding the teaching by FNPs. The teaching skills most
      highly regarded by the students tended to be different than those most highly
      regarded in physicians. CONCLUSIONS: This pilot study suggests FNPs can be
      successfully integrated into undergraduate medical education settings, offering
      teaching strengths that complement those of physicians. Integrating the two
      professions in a family medicine clerkship may prove beneficial to students and
      expand departmental teaching resources without further straining finances.
      Efforts at evaluating the teaching contributions of FNPs at other institutions
      are needed to substantiate the present study results.

PMID- 10916717
TI  - Can a 3-day preceptorship change first-year medical students' opinions about
      living and working in small towns?
AB  - BACKGROUND: Research of medical school initiatives that attempt to orient medical
      students toward rural medicine may facilitate development of initiatives to
      alleviate physician maldistribution. This study investigated the effect of a 3
      day family medicine preceptorship in a small town on first-year medical students'
      opinions about a) living and working in small towns and b) plans to live in and
      practice medicine in small towns. Student feedback about the preceptorship was
      also examined. METHODS: Questionnaires were administered to 137 first-year
      medical students using a separate sample pretest-posttest design. RESULTS:
      Student feedback indicated that the preceptorship was a valuable learning
      experience, but the preceptorship did not appear to influence students' opinions
      about or interest in living in and working in small towns or rural areas.
      CONCLUSION: Brief exposure to rural medicine early in the curriculum appears to
      have little effect on variables that might precede practice location decisions.

PMID- 10916718
TI  - "Ottorino Rossi" Award 2000. New targets for therapy in Parkinson's disease:
      pathogenesis and pathophysiology.

PMID- 10916719
TI  - Autonomic nervous function in de novo parkinsonian patients in basal condition
      and after acute levodopa administration.
AB  - The aims of this study were to assess autonomic nervous function in subjects with
      recently diagnosed Parkinson's disease (de novo patients) and to evaluate its
      changes following acute levodopa administration. In 13 patients (8 males, 5
      females) and 13 age-matched control subjects, three cardiovascular autonomic
      function tests (Deep Breathing, Valsalva, Lying to Standing) were performed, the
      QT interval was calculated on a 12-lead electrocardiogram, and the response of
      plasma norepinephrine to standing was assessed in basal conditions. The
      cardiovascular tests and the measurement of the QT interval were repeated in de
      novo Parkinsonian patients 90 minutes after the administration of levodopa 200 mg
      per os. The results of the Deep Breathing and Valsalva tests were worse and the
      QT interval longer in patients than in control subjects (although the differences
      were not statistically significant). The heart rate increase at 30 seconds after
      standing up was significantly higher in Parkinsonian patients than in the control
      group. The response of plasma norepinephrine to standing was similar in both
      groups. Levodopa administration produced a slight improvement in the Deep
      Breathing test, a shortening of the QT interval and increased tachycardia on
      standing. Our data suggest that a mild subclinical impairment of parasympathetic
      function can be a feature of de novo Parkinsonian patients and that levodopa
      therapy could have a beneficial effect on this autonomic dysfunction.

PMID- 10916721
TI  - Portable blood glucose monitors.
AB  - Blood glucose monitors (BGMs) are used to test the blood glucose levels of
      diabetic patients, both in the home and in hospitals. In the home, BGMs are used
      by patients who monitor their own blood glucose levels. In hospitals, BGMs are
      often used to monitor patients undergoing intensive insulin therapy. In this
      Update Evaluation, we present our findings for 10 newly tested units and compare
      those units with 17 others we've evaluated over the years (most recently in our
      September-October 1997 issue). Because more and more BGMs are designed to meet
      the specific--and increasingly diverging--needs of either home users or hospital
      users, we now rate BGMs for only one use or the other. (In previous studies, we
      rated each model for both applications.) For home/individual use, the main
      selection factors are human-use issues such as whether the unit detects an
      inadequate volume of blood sample (thereby avoiding inaccurate test results) and
      how easily a reading is obtained. For hospital/facility use, perhaps the most
      crucial feature is a data management system to document quality control and
      patient testing information. All the units included in this evaluation exhibit
      adequate performance. But we found some more desirable for their marketed
      applications than others. We rated five of the units Preferred, another 13
      Acceptable, and the remaining nine Not Recommended.

PMID- 10916720
TI  - Migraine as a complex disease: heterogeneity, comorbidity and genotype-phenotype
      interactions.
AB  - Migraine is a chronic illness interspersed with acute signs and symptoms which is
      currently defined, according to IHS criteria, in terms of "attacks". However,
      this should not lead us to ignore a critical point emerging from the simple
      observation of patients, i.e. the variability of the combinations in which the
      disease manifests itself in the same individual and especially in different
      individuals. This heterogeneity underpins both migraine "as attacks" (e.g.
      presence/absence of aura, different pain severity) and migraine "as a disease"
      (e.g. different onset, occurrence, association with other diseases, evolution,
      outcome). Genetic determinants are certainly at the basis of some migraine forms,
      and the role of genetics is now increasing due to the better phenotypical
      characterization rendered possible by the 1988 criteria. In most cases, however,
      migraine occurs as multifactorial inherited character. The level of complexity is
      further increased by the effect of "modifying" genes (such as those encoding for
      dopamine receptors), by comorbidity (the non coincidental association with other
      neurological diseases), and by the fact that the expression of comorbidity varies
      over time (phenotypical heterochronia). The clinical-descriptive approach allows
      only a partial understanding of migraine, the nature of which is more complex and
      heterogeneous than previously thought.

PMID- 10916722
TI  - Diabetes management. Issues in diagnosing and controlling diabetes.

PMID- 10916724
TI  - Failure of movement-control switch on Fischer Traumex x-ray system.

PMID- 10916723
TI  - Loose bolts on Medcare 400002 Stand-N-Weigh (and other) patient lifts may cause
      injury.

PMID- 10916725
TI  - Cracked Hewlett-Packard/Agilent technologies sterilizable defibrillator paddles
      must be replaced.

PMID- 10916726
TI  - Encouraging students with disabilities to pursue careers in bioengineering.

PMID- 10916727
TI  - An introduction to image analysis using mathematical morphology.

PMID- 10916728
TI  - Medical data mining and knowledge discovery.

PMID- 10916729
TI  - A knowledge discovery approach to diagnosing myocardial perfusion.

PMID- 10916730
TI  - Consistent knowledge discovery in medical diagnosis.

PMID- 10916731
TI  - Genetic programming for knowledge discovery in chest-pain diagnosis.

PMID- 10916732
TI  - Discovering knowledge from medical databases using evolutionary algorithms.

PMID- 10916733
TI  - Automated discovery of positive and negative knowledge in clinical databases.
AB  - In this article, the characteristics of two measures, classification accuracy and
      coverage, were discussed. We showed that both measures are dual, and that
      accuracy and coverage are measures of both positive and negative rules,
      respectively. Then, an algorithm for induction of positive and negative rules was
      introduced. The proposed method was evaluated on medical databases, and the
      experimental results show that induced rules correctly represented expert
      knowledge. Several interesting patterns were also discovered.

PMID- 10916734
TI  - Temporal pattern discovery in course-of-disease data.

PMID- 10916735
TI  - Inductive logic programming for knowledge discovery from MRI data.

PMID- 10916736
TI  - Issues in automating cardiac SPECT diagnosis.

PMID- 10916737
TI  - Reactance of biological membranes.

PMID- 10916738
TI  - Modulation transfer functions for quality assurance of mammographic systems.

PMID- 10916740
TI  - Developing and commercializing a DNA sequencer.

PMID- 10916739
TI  - Doppler ultrasound observation of pathological heart valves.

PMID- 10916741
TI  - When does the Freedom of Information Act apply to privately held data produced
      under a Federal grant? (Part I).

PMID- 10916742
TI  - "The Phoenix": 70 years of publishing.

PMID- 10916743
TI  - The development of field guides for birding: Gwillim, Wilson, Audubon and
      Peterson.

PMID- 10916744
TI  - Digital manipulation in scientific images: some ethical considerations.
AB  - Images play a vital role in the publication and presentation of scientific
      research. Large proportions of these images today are produced digitally, and
      these images as well as elements within these images, can be easily enhanced or
      manipulated using electronic darkroom software. This article examines some of the
      ethical issues associated with digital manipulation and offers some suggestions
      on how to deal with them.

PMID- 10916745
TI  - Bringing medical illustration to high school students.

PMID- 10916746
TI  - Biomedical communications: past, present, future.

PMID- 10916747
TI  - Recombinant T-cell receptors: an immunologic link to cancer therapy.
AB  - Cytotoxic T cells can specifically kill target cells that express antigens
      recognized by the T-cell receptor. These are membrane-bound proteins that are not
      ubiquitous and thus are difficult to purify and study at the protein level. The
      advent of recombinant DNA technology has facilitated these objectives, thereby
      enabling researchers to gain valuable information about major T-cell receptor
      characteristics. Genetic manipulation of T-cell receptors has also been used to
      exploit specificity of killing by cytotoxic T lymphocytes, which represents an
      attractive feature for therapeutic purposes. The objective of this review was to
      provide an overview of the major strategies adopted to genetically manipulate T
      cell receptors.

PMID- 10916748
TI  - Long-term survival of anti-tumor lymphocytes generated by vaccination of patients
      with melanoma with a peptide vaccine.
AB  - Immunization with the modified gp100 melanoma peptide gp100:109-217 (210M) in
      Incomplete Freund's Adjuvant (IFA) results in the generation of antipeptide and
      antitumor lymphocytes in the patients' circulation. In this study, the authors
      have evaluated the persistence of these immune cells. Reactivity against the
      native peptide persisted for 138 to 403 days after immunization. Reactivity also
      persisted in three of five patients that received external beam radiotherapy and
      in both patients who received systemic chemotherapy after the completion of
      peptide immunization. Thus, immune lymphocytes with anti gp100:209-217 peptide
      activity appear to persist for prolonged periods after vaccination with modified
      peptide in IFA.

PMID- 10916749
TI  - Amino acid substitutions in the melanoma antigen recognized by T cell 1 peptide
      modulate cytokine responses in melanoma-specific T cells.
AB  - Single amino acid substitutions in melanoma-associated peptides dramatically
      enhance T-cell cytotoxicity against target cells presenting the modified peptides
      (often referred to as heteroclitic peptides). The authors tried to determine
      whether peptide modifications influence other aspects of T-cell immunity toward
      malignant melanoma. A heteroclitic peptide, E26F, with an E to F substitution in
      melanoma antigen recognized by T cell 1 (MART-1)26-35, triggers an enhanced
      tyrosine phosphorylation response when compared with the native- and other
      modified MART-1 peptides. Similarly, the E26F peptide enhances the production of
      mRNA for interleukin (IL)-5, IL-10, IL-13, IL-15, and interferon-gamma and
      significantly enhances release of IL-13 and IL-10 from anti-MART-1 cytotoxic T
      cells. Another heteroclitic peptide, 1L, with an A to L substitution in MART-1(27
      35), also enhances the tyrosine phosphorylation response in anti-MART-1 cytotoxic
      CD8+ T cells. Yet, 1L does not enhance the production of T helper cell type 2
      like cytokines (IL-10 and IL-13). Together these data show that minor amino acid
      modifications of immunodominant melanoma peptides profoundly influence the
      cytokine response in melanoma-specific T cells.

PMID- 10916750
TI  - Induction of cytotoxic T lymphocytes with dendritic cells transfected with human
      papillomavirus E6 and E7 RNA: implications for cervical cancer immunotherapy.
AB  - Human papillomavirus (HPV) infection is associated with cervical cancer. The high
      risk HPV E6 and E7 oncoproteins are constitutively expressed in most cervical
      carcinoma cells, and are, therefore, attractive antigens for cytotoxic T
      lymphocyte (CTL)-mediated immunotherapy. The objective of this study was to
      evaluate the use of dendritic cells (DCs) transfected with RNA encoding the E6
      and E7 protein for cervical cancer immunotherapy. The authors have shown that DCs
      transfected with RNA-encoding antigen stimulate potent antigen-specific CTL
      responses in vitro and in vivo. In this study, they tried to determine whether
      DCs transfected with E6 and E7 RNA stimulate primary, antigen-specific CTL
      responses in vitro. The results show that DCs pulsed with E6 or E7 RNA stimulate
      antigen-specific CTL responses that recognize and lyse DCs transfected with E6
      and E7 RNA and human cervical carcinoma cells expressing the E6 and E7 products,
      and the lysis was comparable to that achieved with E6 and E7 peptide-pulsed DCs.
      Dendritic cells cotransfected with both E6 and E7 RNA stimulate CTLs that are
      more effective at lysing human cervical cancer cells. This study provides a
      rationale for the development of cervical carcinoma immunotherapy using DCs
      transfected with HPV E6 and E7 RNA.

PMID- 10916751
TI  - Quantitation of T-cell receptor frequencies by competitive polymerase chain
      reaction: dynamics of T-cell clonotype frequencies in an expanding tumor
      infiltrating lymphocyte culture.
AB  - The use of T-cell receptor (TCR) genes as markers for antigen-reactive T cells is
      dependent on the ability of the TCR genes to rapidly identify antigen-reactive T
      cell clonotypes in patient samples. We recently reported a competitive reverse
      transcriptase polymerase chain reaction (cRT-PCR) method that can measure the
      frequency of individual TCRBV subfamilies and clonotypes in mixed lymphocyte
      populations more accurately than other semiquantitative PCR assays. However, it
      is impractical to measure changes in the absolute frequency of each TCRBV
      subfamily to identify those T cells with increasing frequency after antigen
      stimulation in vivo or in vitro. Therefore, we have modified our cRT-PCR method
      to more rapidly identify expanding T-cell populations by combining all of the
      TCRBV subfamily-specific competitors into a single sample to determine the
      relative abundance of each TCRBV subfamily. Using an expanding TIL 620 culture,
      we identified four TCRBV (BV2, BV12, BV17, and BV23) subfamilies that expanded
      over a 23-day period. These subfamilies accounted for 23% of the T cells in the
      day 35 culture and increased to 57%, 92%, and 80% of the days 44, 51, and 58
      cultures respectively. Analysis of DNA sequences demonstrated that the observed
      expansion was caused primarily by a single clonotype within each subfamily. T
      cells expressing BV17 and BV23 recognized gp100 and MART-1 respectively.
      Therefore, this cRT-PCR method can detect expanding T-cell populations based
      solely on their TCRBV subfamily expression. Furthermore, T-cell expansion in a
      mixed TIL population was a good predictor of antigen reactivity.

PMID- 10916752
TI  - Enhanced therapeutic potential of adoptive immunotherapy by in vitro CD28/4-1BB
      costimulation of tumor-reactive T cells against a poorly immunogenic, major
      histocompatibility complex class I-negative A9P melanoma.
AB  - Costimulation plays a critical role in T-cell activation and amplification of
      anti-tumor immunity. Although CD28 engagement triggers an early activation
      signal, activation-induced 4-1BB molecule on T cells transmits a crucial signal
      for further expansion and maturation of effector cells. In this report, the
      authors show that costimulation through CD28 and 4-1BB pathways synergistically
      enhances the therapeutic efficacy of T cells from tumor-draining lymph nodes.
      Intravenous adoptive transfer of costimulated T cells into mice bearing
      disseminated micrometastasis of a poorly immunogenic, major histocompatibility
      complex class I-negative A9P melanoma results in a 60% cure rate. Autopsy of mice
      that died after unsuccessful treatment revealed tumor growth in the liver,
      spleen, and skin with minimal or no evidence of pulmonary disease. In contrast,
      mice that received no treatment or noncostimulated T cells had massive pulmonary
      tumors, suggesting that adoptively transferred T cells are less effective against
      growth of extrapulmonary tumors. These results show that costimulation of tumor
      draining lymph node T cells through CD28 and 4-1BB increases their potential for
      cancer immunotherapy and suggests that improper trafficking of tumor-reactive T
      cells to extrapulmonary sites must be improved to enhance clinical efficacy.

PMID- 10916753
TI  - Intracranial paracrine interleukin-2 therapy stimulates prolonged antitumor
      immunity that extends outside the central nervous system.
AB  - To explore the potential efficacy of local cytokine delivery against tumors in
      the central nervous system (CNS), C57BL6 mice were simultaneously given
      intracranial injections of tumor challenge and of irradiated B16F10 melanoma
      cells transduced to secrete interleukin-2 (IL-2). Intracranial IL-2 therapy
      generated antitumor responses capable of extending the survival of animals that
      received simultaneous intracranial tumor challenge either locally or at distant
      sites in the brain. Nontransduced melanoma cells had little effect. Animals that
      survived intracranial IL-2 therapy and tumor challenge showed prolonged survival
      compared with controls when challenged with a second tumor dose 70 days after
      initial treatment. In addition, animals that rejected intracranial tumors were
      also protected from tumor growth upon rechallenge at sites outside the CNS (i.e.,
      subcutaneous tumor challenge). Conversely, identical or 10-fold larger doses of
      IL-2-transduced cells administered by subcutaneous injection failed to generate
      protection against intracranial tumor challenges. Elimination of T-cell and
      natural killer (NK) subsets using gene knockout mice and antibody-depletion
      techniques demonstrated that NK cells were most important for the initial
      antitumor response, whereas CD4+ T-cells were not necessary. These studies
      demonstrate that local IL-2 therapy in the brain not only generates an immediate
      local antitumor immune response, but also establishes long-term immunologic
      memory capable of eliminating subsequent tumor challenges within and outside of
      the CNS. Furthermore, the antitumor response to paracrine IL-2 in the brain
      differed significantly from that in the flank, suggesting that the intrinsic CNS
      cells involved in initiating immunity within the brain have different cytokine
      requirements from their peripheral counterparts.

PMID- 10916754
TI  - Tumor necrosis factor-alpha augments tumor effects in isolated hepatic perfusion
      with melphalan in a rat sarcoma model.
AB  - Isolated hepatic perfusion (IHP) is an attractive approach to treating
      nonresectable liver tumors, because the effects of systemic chemotherapy are poor
      and its application is hampered by severe general toxicity. In clinical and
      experimental settings, the efficacy of isolated limb perfusion (ILP) with tumor
      necrosis factor-alpha (TNF alpha) in combination with melphalan to treat melanoma
      in transit and soft-tissue sarcoma has been well established. In an ILP model in
      rats, the authors previously observed synergistic anti-tumor effects of TNF and
      melphalan on BN 175 soft-tissue sarcoma extremity tumors. The aim of the current
      study was to determine whether similar synergy in anti-tumor effects could be
      achieved by treating experimental BN 175 soft-tissue sarcoma liver tumors by IHP
      using these agents. The authors found that IHP with TNF and melphalan resulted in
      a dramatic increase in regional concentrations of perfused agents with virtually
      no concomitant systemic leakage. Isolated hepatic perfusion with only carrier
      solution resulted in a significantly diminished growth rate of BN 175 liver
      tumors compared with the growth rate of tumors in nonperfused rats. Perfusion
      with melphalan alone resulted in minimal anti-tumor effects. Perfusion with only
      TNF had a slight growth-stimulatory effect on the BN 175 liver tumors, but no
      negative effects on tumor growth were observed. When TNF was added to melphalan,
      a dramatic anti-tumor effect was observed. Thus, as in the rat ILP setting, the
      anti-tumor effect is augmented when TNF is added to IHP with melphalan to treat
      BN 175 soft-tissue sarcoma tumor-bearing rats. Strikingly, the tumor response was
      potentiated at relatively low concentrations of TNF compared with concentrations
      that elicited synergy with melphalan in ILP.

PMID- 10916756
TI  - Increase of the immunostimulatory effect of dendritic cells by pulsing with CA 19
      9 protein.
AB  - Previously, a relative resistance of solid tumor cells to immunologic effector
      cells was shown in vitro. This resistance could be one reason for the clinical
      phenomenon of resistance of patients with colon carcinoma or other solid tumors
      to immunologic therapeutic approaches. In this study, dendritic cells (DCs)
      pulsed with CA 19-9 protein were tested for their immunostimulatory capacity of
      immunologic effector cells against cells derived from colon and pancreatic
      carcinoma. Dendritic cell cultures coexpressed CMRF-44 and CD1a, markers typical
      of DCs, in 31.5% +/- 5.3% after 13 days of culture. Coculture of NK-like T
      lymphocytes with DCs led to a significant increase in cytotoxic activity, as
      measured using a lactate dehydrogenase release assay. Cytotoxic activity could be
      further increased using DCs pulsed with CA 19-9 protein. The effect of CA 19-9 on
      increasing the cytotoxic effect of NK-like T lymphocytes was dose dependent.
      Similarly, cocultivation of DCs with NK-like T cells derived from patients with
      metastatic pancreatic cancer and elevated CA 19-9 serum levels led to a
      significant increase in cytotoxic activity. In conclusion, DCs pulsed with CA 19
      9 protein can increase the cytotoxic activity of immunologic effector cells
      against colon carcinoma and pancreatic cancer cells. Dendritic cells pulsed with
      CA 19-9 protein may have an important effect on immunotherapeutic protocols for
      patients with cancer.

PMID- 10916755
TI  - Induction of tumor-specific immunity in mice by immunization with reconstituted
      tumor membrane liposomes containing recombinant B7-2 (CD86).
AB  - There has been considerable interest in developing experimental vaccines using
      genetically modified tumor cells expressing cytokines or costimulatory molecules
      to enhance immunogenicity. The authors investigated an alternative approach of
      using protein transfer rather than gene transfer to introduce costimulatory
      molecules rapidly into tumor membranes. Immunization with a single dose of
      reconstituted tumor membrane liposomes containing purified recombinant B7-2
      (CD86) induced tumor rejection in mice challenged with syngeneic tumors,
      including the poorly immunogenic AG104A fibrosarcoma. These findings support the
      possibility that cell-free vaccines composed of reconstituted tumor membrane
      liposomes containing additional immunostimulatory proteins may offer a practical
      and safe alternative to genetically modified tumor cells for treating human
      cancer.

PMID- 10916757
TI  - Anti-tumor activity of K1-LysPE38QQR, an immunotoxin targeting mesothelin, a cell
      surface antigen overexpressed in ovarian cancer and malignant mesothelioma.
AB  - Mesothelin, a differentiation antigen, is a 40-kD glycosylphosphatidylinositol
      linked cell-surface glycoprotein, that is present on the surface of normal
      mesothelium and is overexpressed in many patients with epithelial ovarian cancer
      and malignant mesotheliomas. Monoclonal antibody K1 is a murine immunoglobulin G1
      that recognizes mesothelin. LysPE38QQR is a truncated form of Pseudomonas
      exotoxin that lacks the cell-binding domain, but retains the translocation and
      adenosine diphosphate-ribosylation domains. It has a single lysine residue near
      the amino terminus that is available for conjugation to antibodies. To prevent
      chemical conjugation of the antibody to lysine residues at the C-terminus of
      Pseudomonas exotoxin, the two lysine residues at positions 590 and 606 were
      mutated to glutamine, and the lysine residue at position 613 was mutated to
      arginine. Monoclonal antibody K1 was chemically conjugated with LysPE38QQR, by
      modifying the antibody with sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1
      carboxylate and coupling it with SPDP N-succinimidyl 3-(2
      pyridyldithio)propionate-modified LysPE38QQR. The resulting immunotoxin K1
      LysPE38QQR was highly toxic to A431-K5 cells (a human epidermoid carcinoma cell
      line transfected with a mesothelin expression plasmid) with a half-maximal
      inhibitory concentration of 3-6 ng/mL. The immunotoxin had negligible activity
      against A431 cells, which do not express mesothelin (median inhibitory
      concentration > 100 ng/mL). This immunotoxin also caused complete regression of
      tumors in nude mice that received xenografts of mesothelin-positive human
      carcinomas. These results show that immunotoxins directed against mesothelin are
      a therapeutic option that merits further investigation for the treatment of
      ovarian cancer and malignant mesotheliomas.

PMID- 10916758
TI  - Augmentation of 17-1A-induced antibody-dependent cellular cytotoxicity by the
      triple cytokine combination of interferon-alpha, interleukin-2, and interleukin
      12.
AB  - Previously, interferon-alpha (IFN-alpha), interleukin-2 (IL-2), and interleukin
      12 (IL-12) were shown to increase the antibody-dependent cellular cytotoxicity
      (ADCC) induced by the murine monoclonal antibody 17-1A, which recognizes the
      tumor-associated antigen EpCAM. In this study, the authors wanted to determine
      whether the combination of these three cytokines would yield greater cytotoxicity
      than the single cytokines. For cytotoxicity assessment, a new flow cytometric
      assay was used that allows the analysis of long-term ADCC exerted by macrophages.
      Peripheral blood mononuclear cells from healthy donors were used as effector
      cells against the colorectal carcinoma cell line HT29 at a low effector-to-target
      ratio of 4.5:1. With this test, the effectiveness of the combinations IL-2 and
      IFN-alpha, IL-2 and IL-12, and IL-12 and IFN-alpha were compared with each other.
      The combinations IL-2 plus IL-12 and IFN-alpha plus IL-12 were more potent at the
      concentrations tested. Furthermore, the triple cytokine combination of IFN-alpha,
      IL-2, and IL-12 revealed significantly greater ADCC than dual cytokine
      combinations. Next, CD14+, CD4+, and CD4- cells were isolated by paramagnetic
      beads and magnetic activated cell sorter (MACS) columns. The CD14+ and CD4- cell
      populations contained the ADCC effectors. The addition of CD4+ cells to CD14+ or
      CD4- cells resulted in augmented ADCC, indicating that cooperation between immune
      cells occurs. These results suggest that multiple cytokine combinations with
      monoclonal antibodies may be more effective for cancer immunotherapy.

PMID- 10916759
TI  - Phase 1 study in patients with metastatic melanoma of immunization with dendritic
      cells presenting epitopes derived from the melanoma-associated antigens MART-1
      and gp100.
AB  - Dendritic cells (DCs) have been shown to enhance anti-tumor immune responses in
      several preclinical models. Furthermore, DC-like function can be elicited from
      peripheral blood monocytes cultured in vitro with interleukin-4 and granulocyte
      macrophage colony-stimulating factor. For this reason, a phase 1 study was
      initiated at the Surgery Branch of the National Cancer Institute to test the
      toxicity and biological activity of the intravenous administration of peripheral
      blood monocyte-derived DCs. The DCs were generated by 5- to 7-day incubation in
      interleukin-4 (1,000 U/mL) and granulocyte-macrophage colony-stimulating factor
      (1,000 U/mL) of peripheral blood monocytes obtained by leukapheresis. Before
      administration, the DCs were pulsed separately with the HLA-A*0201-associated
      melanoma epitopes MART-1(27-35) and gp-100-209-2M. The DCs were administered four
      times at 3-week intervals. A first cohort of patients (n = 3) was treated with 6
      x 10(7) DCs and a second cohort (n = 5) with 2 x 10(8) DCs (in either case, one
      half of the DCs were pulsed with MART-1(27-35) and the other half was pulsed with
      gp-100-209-2M). In a final cohort under accrual (n = 2) 2 x 10(8) DCs were
      administered in combination with interleukin-2 (720,000 IU/kg every 8 hours). The
      recovery of DCs after in vitro culture ranged from 3% to 35% (mean, 15%) of the
      original peripheral blood monocytes. Administration of DCs caused no symptoms at
      any of the doses, and the concomitant administration of interleukin-2 did not
      cause toxicity other than that expected for interleukin-2 alone. Monitoring of
      patients' cytotoxic T lymphocyte reactivity before and after treatment revealed
      enhancement of cytotoxic T lymphocyte reactivity only in one of five patients
      tested. Of seven patients evaluated for response, one had a transient partial
      response with regression of pulmonary and cutaneous metastases. A relatively
      large number of DCs can be safely administered intravenously. The poor clinical
      outcome of this study perhaps could be explained by the type of protocol used for
      DC maturation, the route of administration, or both. For this reason, this
      clinical protocol was interrupted prematurely, whereas other strategies for DC
      preparation and route of administration are being investigated at the authors'
      institution.

PMID- 10916760
TI  - Feasibility of the adoptive transfusion of allogenic human leukocyte antigen
      matched natural killer cells in patients with renal cell carcinoma.
AB  - Patients with metastasized renal cell carcinoma have a poor prognosis with
      conventional therapies. The feasibility and safety of donating purified natural
      killer (NK) cells without additional cytokines were evaluated. In contrast to all
      previous studies, the NK cells were derived from allogenic donors. The NK cell
      donors were HLA-C matched to enable NK cell inhibition via killer cell inhibitory
      receptors and HLA-C. This should obviate a graft-versus-host reaction against
      nonmalignant HLA-expressing tissues in the allogenic constellation. The average
      number of cells applied per transfusion was 1.02 +/- 0.265 x 10(9). The purity of
      the NK cells was 85% to 95%, and most of the contaminating cells were monocytes.
      Twenty-six transfusions given to 11 patients did not cause any minor or major
      adverse effects, with the exception of one episode of transient fever. One
      patient had an objective regression of his lung metastases that had been
      progressing continuously before. No cytotoxic HLA antibodies could be detected 3
      weeks after the transfusions. The observed tolerance to this therapeutic regimen
      suggests the need for further studies with increased doses of cytokine-activated
      NK cells.

PMID- 10916762
TI  - Autoimmune hemolytic anemia in a patient with chronic lymphocytic leukemia and
      renal cell carcinoma after treatment with high-dose intravenous bolus interleukin
      2.

PMID- 10916761
TI  - TNF registered in Europe: does TNF get a second chance?

PMID- 10916763
TI  - "The write stuff".

PMID- 10916764
TI  - The case history.
AB  - Case histories report the basic data of psychoanalysis, and yet they are
      strikingly infrequent in the psychoanalytic literature. This reflects not only
      the methodological problems in describing psychoanalytic cases, but also the
      complex intentions of psychoanalysts who want both to present and to conceal
      aspects of their work. The history of the case history is discussed, as are the
      nature and purpose of case reports, the differences between oral and written
      reports, the relation between case reports and psychoanalyses, and case reports
      as countertransferential enactments. A plea is made for including authorial
      intention as an explicit part of the report, rather than concealing it behind a
      scientific facade.

PMID- 10916765
TI  - On writing from clinical experience.
AB  - Papers that present the life of the analytic session offer material through which
      analysts can together study analytic process and therapeutic action and arrive at
      consensus on how to improve psychoanalytic theory and practice. But some analysts
      have been deterred from publishing clinical material of that kind because of
      concerns about preserving confidentiality, protecting the therapeutic
      relationship, reporting accurately, being scrutinized, worrying about losing
      their colleagues' support, and not feeling authorized to present their views.
      Here conscious, preconscious, and unconscious constraints against writing and
      publishing are explored, and an example is given of successful self-analysis of a
      writing inhibition. The debate over the ethics of writing is reviewed and an
      argument made that detailed clinical description is useful in advancing analytic
      understanding. Finally, a clinical example shows how the analysand usefully
      analyzes the experience of reading what the analyst has written, and how the
      analyst's self-analysis may be promoted in resonance with the analysand's
      experience.

PMID- 10916767
TI  - Clinical discussants as psychoanalytic readers.
AB  - Psychoanalytic discussants of clinical papers face certain tasks, opportunities,
      and difficulties. To be willing to present and publish their analytic work for
      colleagues to study, analyst-authors and discussants need to expect that the
      other will respectfully complement his or her perspective. Discussants are
      encouraged to immerse themselves playfully in the affective force-field
      constituted between analysand and analyst within the process of the presentation.
      As discussants struggle to extricate themselves from this force-field, they
      contribute best by confining their understandings to the presentation process
      rather than trying to pin down the actual psychoanalytic situation. When this is
      done, discussants are under less pressure to inform presenters. This paper
      considers how discussants need to process their feeling responses to clinical
      papers so as to enhance rather than injure the analyst-author. This approach is
      illustrated with vignettes of the author's efforts as a clinical discussant to
      become a constructive psychoanalytic reader.

PMID- 10916766
TI  - Why we need to write openly about our clinical cases.
AB  - To learn more about what is and is not effective in the psychoanalytic situation,
      analysts need to develop a library of detailed analytic case material. Open case
      writing, by not overconstraining readers, allows them enough access to the
      analytic couple's affective experience to persuade them of the authenticity and
      validity of the analyst-author's views. They are then free to rethink the
      material creatively on their own, to use it as they need to, and to learn from
      others, in order to enhance their analytic skills. Closed case writing hinders
      readers' creative freedom to understand and interpret, and hence to learn. To
      encourage analyst-authors to share their affective experiences in the analytic
      situation more openly, analysts need to establish a constructively collaborative
      attitude toward playing with clinical material. They need to take for granted
      that new readers, even authors themselves newly rereading their work, will
      discover something new. A dialectical process can then be established in which
      clinical authors and readers contribute to each other in an ongoing imaginative
      interchange.

PMID- 10916768
TI  - A semiotic model of mind.
AB  - A theory of signs is presented to arrive at a model of mind that provides a
      smooth transition from inanimate matter to the thinking brain. Principles of
      information theory and semiotics are invoked to create a conceptual scheme that
      can contribute to an understanding of the "mind-body problem." The thesis is
      pursued that in living systems, as opposed to inorganic ones, there occurs the
      phenomenon of semiotic transmission of information. The result is a "dualistic
      materialist" position; the dualism arises from the fact that at the beginning of
      life a set of processes comes into being different from those of the inorganic
      world. This model has implications for psychology and psychoanalysis. It allows
      for semiotic systems at different levels--e.g., the molecular, the neural
      network, the language system, and higher mental functions--to be integrated.
      Analytic concepts such as free association, clinical technique, feedback systems,
      personality structure, transference, and repetition compulsions can be understood
      in both biological and semiotic terms. This model interdigitates with linguistic
      studies already done in psychoanalysis, as well as with biological models
      extrinsic to the field.

PMID- 10916769
TI  - The mapmaker's dilemma: introduction to panels.

PMID- 10916770
TI  - Subjectivity and objectivity in the analyst.

PMID- 10916771
TI  - Spontaneity versus constraint: dilemmas in the analyst's decision making.

PMID- 10916772
TI  - Supervision as an intersubjective process: hearing from candidates and
      supervisors.

PMID- 10916773
TI  - Countertransference, self-examination, and interpretation.

PMID- 10916774
TI  - Meet the author: Fred Busch.

PMID- 10916775
TI  - Lawrence Friedman and the trouble with "reality".

PMID- 10916776
TI  - No self-disclosure, just a typo.

PMID- 10916777
TI  - [Expression of AC133 vs. CD34 in acute childhood leukemias].
AB  - AC133, a newly discovered antigen on human progenitor cells, demonstrating 5
      transmembranous domains is expressed by 30-60% out of all CD34+ cells. Our aim
      therefore was to investigate the extent of human stem-/progenitor cells
      expressing AC133 antigen in umbilical cord blood, peripheral blood without or
      following an application of granulocyte-colony stimulating factor (rhG-CSF). The
      main task was the investigation of bone marrow aspirates derived from children
      suffering from newly diagnosed acute leukemias, as well as from patients with a
      relapse or during a complete remission. The determination of antigen expression
      was done by application of flow cytometry (FACScan analysis) and the usage of
      newly developed monoclonal antibodies (AC133/1 and AC133/2; Miltenyi Biotec GmbH)
      in combination with monoclonal antibody directed against CD34-antigens (HPCA-2;
      BD). Our studies till now show average percentages in umbilical cord blood
      derived from 43 newborns about 0.294 +/- 0.165% AC133+ vs. 0.327 +/- 0.156% CD34+
      hematopoietic stem-/progenitor cells (HSPC). In peripheral blood from 11 healthy
      donors we verified up to 0.15% CD34+ as well as AC133+ HSPC's. The concentration
      of progenitor cells was found to be obviously higher in peripheral blood from
      children with various diseases (neuroblastoma, rhabdomyosarcoma, ALL/AML) and
      undergoing application with rhG-CSF in order to be prepared for PBSC
      transplantation. In those cases we found up to 3.51% AC133+ cells as well as
      slightly higher values (3.94%) for CD34 antigens. Additionally we quantified 128
      bone marrow (BM) samples for AC133+ and CD34+ cells. In 10 BM samples, derived
      from patients without any neoplasia, the CD34+ cells were about 0.03% and 1.49%,
      whereas AC133 values were up to 0.64%. Bone marrow aspirates from 53 children
      with acute leukemias at time of diagnosis (ALL: n = 41/AML: n = 12) have been
      immunophenotyped and leukemic blast cells have been proved for AC133- and CD34
      antigen expression. 32/41 (78%) of lymphoblastic leukemic cells showed to be
      positive for CD34 antigen and 24/41 (58%) demonstrated AC133 antigens.
      Interestingly there were 2 ALL-patients with pathological blast cells positive
      for AC133 but lacking of any CD34 antigens. 42% (5/12) of investigated AML
      patients showed CD34+ phenotype, on the other hand there were only 25% (3/12)
      with AC133+ phenotype. Similar values were found in relapsed patients (n = 18).
      In BM samples from patients during complete remission (n = 47) we could detect
      percentages up to 5.55% for CD34 and up to 1.25% for AC133 positive stem
      /progenitor cells. Such quite high data may be explained by occasionally
      application of rhG-CSF therapy. Our results till now lead to the conclusion, that
      it seems to be useful, to recruit quantification of CD34+ HPSC by additionally
      detecting AC133 antigens. This new stem cell marker (AC133) may be of great value
      in case of autologous peripheral blood stem cell transplantation (PBSCT) because
      it could be an alternative to the usual CD34+ MACS selection system.

PMID- 10916778
TI  - [Steroids for prophylaxis of nephropathy in Schnlein Henoch purpura? Follow-up of
      171 patients].
AB  - The necessity of the controversially discussed general steroid prophylaxis in
      Henoch-Schonlein Purpura (HSP) was analysed based on frequency, risk factors and
      prognosis of renal involvement. Case histories and follow up of at least 1.5
      years were evaluated in all 171 patients (median age 6 years) in our institution
      suffering from HSP between 1.1.1987 and 30.6.1997. HSP was frequently manifest
      with an involvement of joints (64%) and gastrointestinal tract (58%). Renal
      involvement occurred in only 29% of the children. Excepted one girl (age 12
      year), all children with renal disease completely recovered. Renal involvement
      was significantly rarer in young children (16%) and after one week therapy with
      prednisone (7%). In young children, renal involvement always followed abdominal
      pain. CONCLUSION: In our collective, a general preventing of renal disease in HSP
      was unnecessary. Especially in young children, the most common manifestation age,
      renal involvement rarely occurred and had always a good prognosis.

PMID- 10916779
TI  - [Autoimmune thyroiditis in children and adolescents: clinical and laboratory
      findings in 34 patients].
AB  - Autoimmune thyroiditis (AT) is the most common cause of nonendemic thyromegaly
      and acquired hypothyroidism in childhood and adolescence. Outgoing from an
      increasing number of newly diagnosed patients during the last years we performed
      a retrospective analysis including 34 patients treated between 1989 and 1998.
      Clinical data, laboratory and sonographical findings are described. Cases were
      ascertained by palpable thyroid enlargement or clinical signs of thyroid
      dysfunction and positive autoantibodies against thyroid tissue. Frequency of AT
      diagnosis has threefold increased since 1995 in our department. Age at diagnosis
      was 5.4 to 16.3 years (median 11.3). Palpable thyromegaly was present in 29 (85%)
      of our patients. Three patients had myxedema without goiter. Symptoms had been
      present for a period between 6 weeks and 7.5 years: median in all patients 6
      months, median in hypothyroid patients 9 months. At time of diagnosis 15 patients
      suffered from hypothyroidism, 3 from hyperthyroidism and 7 patients showed normal
      levels of thyroid hormones. In 9 patients we found an isolated elevation of
      thyrotropin. 12 patients were prepubertal (Tanner I), 15 patients were pubertal
      (Tanner II-IV). 5 patients showed a dissociation of pubertal maturation.
      Ultrasound of thyroid gland showed an inhomogeneous and hypoechoic pattern in 32
      patients. 30 patients were treated with thyroxine. Patients with persistent
      hyperthyroidism were treated with carbimazol. During the follow-up period
      enlargement of the thyroid gland decreased in one third of the patients.
      Thyromegaly caused by autoimmune thyroiditis gets an increasing importance. The
      high degree of obviously hypothyroid patients at the time of diagnosis reflects a
      delay of diagnosis. Early recognition and treatment of the disease should be
      achieved for a preventive care of hypothyroidism.

PMID- 10916780
TI  - [Hereditary fructose intolerance (HFI) as cause of isolated gamma GT rise in a 5
      year old boy with hepatomegaly].
AB  - The diagnosis of HFI is easily missed during childhood. It should be suspected in
      children presenting with hepatomegaly and an isolated increase in GGT. A
      carefully taken nutritional history forms the basis of the diagnosis of HFI which
      can be confirmed by molecular analysis with a sensitivity of > 95%. I.v. fructose
      tolerance tests and liver biopsies often can be omitted.

PMID- 10916781
TI  - [Sacral osteoid osteoma--a rare cause of back pain in childhood and adolescence].
AB  - Osteoid-osteoma should be included in the differential diagnosis of any young
      patient with pain in the back. The tumor is the most common cause of painful
      scoliosis in adolescents. In spite of typical symptoms the diagnosis is often
      delayed. The osteoid-osteoma is seldom located in the sacrum and it can be
      difficult to diagnose the lesion by plain radiography there. At best, the
      radiographs may show an area of perifocal sclerosis. Scintigraphy and computed
      tomography can establish the diagnosis. Therapeutic procedures are medical
      treatment, operative excision or percutaneous radiofrequency coagulation. We
      report the case of a thirteen year old boy who suffered from an osteoid-osteoma
      in the sacrum.

PMID- 10916782
TI  - [3-hydroxy-3-methylglutaraciduria (case report of a female Turkish sisters with 3
      hydroxy-3- methylglutaryl-Coenzyme A lyase deficiency].
AB  - 3-Hydroxy-3-methylglutaric aciduria is a rare inborn error of metabolism, caused
      by reduced enzyme activity of the intramitochondrial 3-hydroxy-3-methylglutaryl
      CoA lyase. We describe two turkish sisters with this disease. In the older sister
      clinical symptoms with lethargy, convulsions, metabolic acidosis, hypoglycemia
      and hyperammonemia lead to the diagnosis. The younger sister was diagnosed
      prenatally. The clinical course of our patients is compared with those reported
      in the literature with respect to clinical symptoms, differential diagnosis and
      therapeutic regimens.

PMID- 10916783
TI  - [Incipient spinal cord compression syndrome due to a herniation of calcified
      intervertebral disk in a young girl].
AB  - Intervertebral disc calcification in childhood is rare. Calcifications are
      discovered by occasion during routine examinations of healthy children or evoke
      symptoms like neck and shoulder pain or discrete neurological symptoms. The
      prognosis of nearly all patients is excellent. We report on a 11-year-old girl,
      who suffered from acute pain in the neck and the left shoulder with increasing
      paresthesias of her left extremities which led to hospitalisation. Intervertebral
      disc calcifications were found between several cervical and thoracic vertebra.
      The only paraclinical finding was an elevated erythrocyte sedimentation rate.
      After 12 days of conservative and analgetic treatment the clinical condition
      deteriorated with acute worsening of the neck pain. The MRI revealed a posterior
      herniation of a calcified disc between the lower cervical spine with spinal cord
      compression. Immediate neurosurgical intervention led to decompression and
      disappearance of the symptoms. After 14 months the clinically healthy child only
      showed the persistence of one intervertebral disc calcification and a complete
      resolution of the former findings.

PMID- 10916785
TI  - [Urinary tract infection by Staphylococcus saprophyticus in a child].
AB  - Staphylococcus (S.) saprophyticus belongs to the coagulase-negative staphylococci
      and is the cause of urinary tract infections, especially in young women, rarely
      in children and in elderly men. Probably the real incidence of urinary tract
      infections due to these organisms is higher than usually accepted. We report on a
      11 3/12-year-old girl, who developed symptoms of a urinary tract infection
      (dysuria, flank pain), but without fever and elevated CRP. In the bladder
      aspirate we found leukocytes and S. saprophyticus (cotrimoxazole-resistant).
      Ultrasound detected intrarenal doubling, but no typical anomalies, disposing for
      urinary tract infections. The treatment with cefuroxim i.v. and clindamycin p.o.
      was successful. CONCLUSION: Coagulase-negative staphylococci cultivated in urine
      represent contamination (mostly S. epidermidis--except in patients, who have
      undergone manipulation or catheterization of the urinary tract) or they are the
      cause of an urinary tract infection (mostly S. saprophyticus).

PMID- 10916786
TI  - [Myositis caused by a mycoplasma infection].
AB  - Mycoplasma pneumonia infection can be associated with neurological manifestations
      such as meningoencephalitis, cerebellitis, aseptic meningoitis,
      polyradiculopathy, transverse myelitis, cranial nerve palsies and myositis [4,
      5]. We report a case of a white female 11 years, 2 months old child, who
      presented with a 3 day history of pain in the left leg. The electromyograpy
      showed pathological signs. We found a serological titer of IgM antibodies for
      Mycoplasma pneumoniae. By treatment with erythromycin the complaints improved
      quickly. CONCLUSION: A myositis can be caused with an infection with Mycoplasma
      pneumoniae. The differential diagnosis is essential.

PMID- 10916784
TI  - [Symptomatic Langerhans-cell-histiocytosis of the cervical spine in a child: case
      report].
AB  - We report on a six year old female presented with a painful torticollis and a
      hemidysaesthesia caused by destruction of the third cervical vertebra and a
      paravertebral soft-tissue mass. At diagnostic routine finally a biopsy gives the
      diagnosis of Langerhans cell histiocytosis. In a second open approach the
      destructed vertebral body was replaced by a precisely adjusted autologous bone
      interponate and the patient was maintained in halo vest immobilisation. The
      outcome is described and an overview of the current literature is given.

PMID- 10916787
TI  - [The efficacy of corticosteroids in exacerbations of chronic obstructive
      pulmonary disease: meta-analysis of published studies].
AB  - BACKGROUND: Corticosteroids are frequently used in exacerbations of chronic
      obstructive pulmonary disease (COPD), but their efficacy is controversial. We
      have carried out a systematic review of the literature to clarify this issue.
      METHODS: We searched Medline, Cochrane Library and Indice Medico Espanol
      databases for articles about corticosteroids and COPD. Placebo-controlled studies
      were selected and reviewed independently by two investigators. RESULTS: We found
      no studies using inhaled corticosteroids. Six studies analysed the effect of
      systemic corticosteroids. They showed a significant improvement of FEV1 by three
      days (weighted mean difference between placebo and treated groups 89 ml; CI 25
      153; 4 trials) and by 7-14 days (200 ml; CI 7-393; 3 trials). The duration of
      hospitalisation was also shorter in patients receiving corticosteroids (p =
      0.03). There also was a non-statistically significant trend towards a lower
      failure rate in treated groups, without differences in mortality rate. At
      midterm, the differences in FEV1 disappeared. CONCLUSION: Corticosteroid
      administration by systemic route is associated with a clinically relevant short
      term improvement in spyrometric values. Although there are no clear differences
      in prognostic variables, these data give support to the practice of using these
      drugs for short periods, not longer than two weeks.

PMID- 10916788
TI  - [Prevalence and risk factors of respiratory symptoms in farmers; comment].
AB  - BACKGROUND: A cross-sectional study was performed to determine the prevalence of
      respiratory symptoms in farmers and to assess occupational risk factors for
      respiratory symptoms in this population. METHOD: A questionnaire on respiratory
      symptoms and occupation was mailed to a sample of 1,191 farmers with descriptive
      analysis of the symptoms and multivariate analysis through logistic modeling to
      assess the different risk factors. RESULTS: 1,164 workers answered the
      questionnaire (response index 98.2%) and 808 subjects were finally included in
      the study after discarding non exposed workers. The highest prevalences of asthma
      symptoms (39.2%) and symptoms of nasal allergy (31.6%) were found in poultry
      workers (p < 0.001, chi square). Sheep workers showed the highest prevalences of
      chronic phlegm (38.5%), work-related symptoms (53.9%) and symptoms of organic
      dust toxic syndrome (35.9%) (p < 0.005, chi square). At multivariate analysis,
      adjusting for age, gender, smoking and other occupational exposures, poultry work
      was a risk factor for asthma symptoms (OR 2.1; IC 95% 1.2-3.8) and symptoms of
      nasal allergy (OR 2.3, IC 95% 1.3-4.2), and dairy farming a risk factor for
      chronic phlegm (OR 1.8, IC 95% 1.1-2.9). Agriculture was not associated with
      respiratory symptoms. CONCLUSION: In our study risk factors for respiratory
      symptoms in Spanish farmers were poultry and dairy farming.

PMID- 10916790
TI  - [Glucocorticoids in the treatment of chronic obstructive pulmonary disease].

PMID- 10916789
TI  - [Influence of a day care hospital on the incidence of hospital admission of AIDS
      patients].
AB  - BACKGROUND: Day care units have become an usual way of medical care for AIDS
      patients. However, their influence on the incidence of hospital admissions has
      not been evaluated. METHODS: Observational and longitudinal study of a cohort of
      308 patients with aids diagnosed between 1990 and 1994 and followed-up to June
      1996. The incidence of hospital admissions according to the hospital of follow-up
      (with or without day care unit) was analyzed. A multivariate analysis of the
      number of hospital admissions was performed using regression model adjusted to a
      distribution of Poisson. RESULTS: After AIDS diagnosis, the incidence of hospital
      admissions was 108 per 100 patient-years of follow up (21 days as inpatient per
      patient-year). Those patients controlled in the hospital with day care unit have
      less hospital admissions (relative risk after adjusting by CD4+ cells count and
      type of diagnostic disease: 0.64; CI95% 0.55-0.76), and less days as inpatient
      through their follow-up (11 to 31 days less). There was no difference in survival
      among patients followed in both hospitals. CONCLUSIONS: A day care unit decrease
      the incidence of hospital admissions in aids patients. This positive impact is
      more evident in patients with lesser CD4+ cell counts.

PMID- 10916792
TI  - [Genes and environmental factors in the development of asthma and atopy].

PMID- 10916791
TI  - [Is the country-side harmless?].

PMID- 10916793
TI  - [New perspectives in Continuous Medical Education (CME): use of new
      telecommunication technologies].

PMID- 10916794
TI  - [Thirty-eight-year-old male with pernicious anemia and gastric polyps].

PMID- 10916795
TI  - [Absence of antiviral activity of high-dose subcutaneous beta-interferon in
      patients with chronic infection by genotype 1 virus C hepatitis].

PMID- 10916796
TI  - [Splenic brucellosis-related abscess].

PMID- 10916797
TI  - [Spontaneous hemothorax secondary to fracture of solitary costal exostosis].

PMID- 10916798
TI  - [Evidence of the efficacy of hypocholesterolemic treatment in primary and
      secondary prevention of ischemic heart disease].
AB  - Good clinical medicine is, nowadays, not based on personal experiences, but in
      the results of broad prospective controlled studies considering the experience of
      many professionals, which in the case of new therapeutic options are named
      clinical trials. Several evidences of the determinant role of cholesterol in the
      development of atherosclerosis are reviewed. Pathologic studies illustrate the
      presence of cholesterol in atheroma plaques, with a good correlation between the
      severity of lesions and the amount of cholesterol in the plaques. Animal
      experiences demonstrate that hypercholesterolemia, rarely spontaneous, usually
      induced with dietary modifications, induces atherosclerosis in animals.
      Observation of patients with genetic-based hypercholesterolemia shows a high
      frequency of coronary atherosclerosis among them, and the broad cohort studies
      corroborate a good correlation between cholesterolemia and coronary heart
      disease. Finally, hypolipidemic intervention trials, mainly with drugs, and
      specially with statins, have clearly defined the benefits in coronary risk
      reduction.

PMID- 10916799
TI  - [Validity of clinical tests to confirm or exclude the diagnosis of acute
      myocardial infarction].
AB  - BACKGROUND: To know the clinical usefulness of the diagnostic tests habitually
      used to diagnose an acute myocardial infarction (MI), in a group of patients in
      which this diagnosis is clinically highly suspected. PATIENTS AND METHODS: A
      cross sectional study was designed. The sample (n = 114) was randomized and
      selected by term and specific of days from the patients attending the Emergency
      Service at Elda General Hospital (Alicante, Spain) in a year period. The method
      we used was is a validity study, making 2 x 2 tables. The clinical outcome was
      the gold standard and was cross matched with some of the clinical criteria
      habitually used to diagnose acute myocardial infarction: thoracic pain character,
      irradiation, ECG findings and CK-MB levels. RESULTS: Clinical suspicion of MI was
      confirmed in only 27.8% (IC--95%: 19.3-36.3). The best validity indexes of
      clinical usefulness to confirm the MI diagnosis were obtained from ECG findings
      (CP+ = infinity) and CK-MB (CP+ = 24.2 at the end of the observational period and
      CP = 17.9 at the beginning). The best negative clinical validity indexes were CK
      values obtained at the end of the observational period (CP- = 0.07) and the ECT
      findings obtained at the end of the observational period (CP- = 0.10).
      CONCLUSION: Clinical carefulness is essential to avoid a diagnostic mistakes in
      MI patients, since the symptoms we used as a diagnostic guide do not offer good
      validity indexes. Changes in ECG or CK-MB levels could confirm the MI diagnosis
      but normal findings in both tests did not discard this diagnosis. We should keep
      the possibility of a mistake till the end of the observational period.

PMID- 10916800
TI  - [Local variability in the guidelines for hypertension screening, diagnosis and
      baseline assessment in 40 health centers].
AB  - BACKGROUND: To identify and to compare the recommendations of the currently
      existing clinical protocols for arterial hypertension (HT) screening, diagnosis
      and baseline study in the Murcia Region, Spain, in order to assess their validity
      and reliability. MATERIAL AND METHODS: Structured comparative description of
      guidelines in Clinical Protocols for HT (n = 40) from all Health Centers in the
      Region. Comparative description of the Health Centers Clinical Protocols and
      national and international reference documents regarding HT screening, diagnosis
      and baseline assessment is performed. RESULTS: Target population for screening
      ranged from aged > or = 14 years (24 centers) to > 20 (1 center). Screening
      procedure was not described in 3 centers and screening periodicity varied from 6
      months to 5 years, with differences by age and by concurrent risk factors in some
      protocols. Diagnosis norms differed by age in only 11 protocols; blood pressure
      (BP) exams for diagnosis varied from 3 to 5 and there were 12 different HT
      figures for immediate diagnosis and treatment. Baseline study varied greatly; we
      found a total of 7 recommended items for anamnesis, 11 for physical exam, 19 for
      blood tests, 4 for urine tests, and 7 for other tests; only the electrocardiogram
      was common to all protocols. There was also some disagreement in the national and
      international reference guidelines whose scientific evidence was not always
      explicitly considered. CONCLUSIONS: There is a wide local variation in norms for
      HT screening, diagnosis, and baseline study. If the Centers follow their own
      protocols, the same patient may be or may not be diagnosed depending on the
      Center he visits; additionally, there would be big differences in the process and
      resources needed for HT control. This variation casts doubt on the protocols
      validity and reliability at regional level and underscores the need for
      critically reviewing the validity of existing protocols.

PMID- 10916801
TI  - [Mapping the scientific evidence for bedside care to unstable angina. A
      preliminary step to develop clinical guidelines. The name of the study group
      CAMBIE Change in the Medical services based on the clinical practice guidelines].
AB  - BACKGROUND: The uncertainty in clinical practice arise from the need of
      physicians to make decisions on a limited ground of knowledges. Guidelines are
      supposed to facilitate clinical decisions in such circumstances. Sharing
      knowledges on natural history of diseases and clinical expertise allow to define
      and array of steps structured on a formal flow-chart. The node of algorithms
      identifies decisions to analyze. This paper presents a taxonomy of specific
      questions related to each decision nodes for management of unstable angina and
      assesses the level of evidence available for each question. MATERIAL AND METHOD:
      A flow chart diagram display the conceptualized key nodes for clinical management
      of unstable angina. A set of specific question related to clinical exclusive
      circumstances, diagnostic approach, utility of diagnostic procedures, definition
      of prognosis and outcomes was raised for each decision node. From a systematic
      literature review the best available evidence was gathered. Each recommendation
      was linked to a level (A-C) of evidence, and to a body of consensus expert panel
      decisions. RESULTS: 34 decision nodes were identified, related with at least 1
      question for appraisal of the best evidence. The solution to these questions
      yielded 40 recommendations scored by the strength of the evidence available. Five
      recommendations of diagnostic, 20 at prognostic and 15 at therapeutic step. The
      strength of evidence was A for 73% of recommendations at therapeutic step versus
      40% at the two other steps. CONCLUSIONS: A clinical complex problem can be
      displayed in a continuous process, to allow identification and appraisal of
      decisions at different clinical nodes. The work-up to achieve a conceptualization
      of a clinical problem is the preliminary step to develop clinical practice
      guidelines. Identification of decision nodes allows to manage uncertainty in a
      explicit way and make policy statement more acceptable by managers and
      physicians.

PMID- 10916802
TI  - [Angiotensin converting enzyme inhibitors in arterial hypertension and cardiac
      failure. The question of the dose].
AB  - The clinical use of the angiotensin enzyme converter inhibitors (AECI) has
      represented one of the main advances in medicine in the last quarter of a
      century. Assuming the pathogenic pluripotentialness of cardiovascular diseases
      (arterial hypertension, atherosclerosis, cardiac failure etc.), from the
      currently available experimental and clinical evidence of these compounds, it may
      be said that the mechanisms of action of the AECI make them to be the first
      pharmacologic group in cardiovascular medicine to have true pluripotentialness.

PMID- 10916803
TI  - [Evidence of the therapeutic effect of antihypertensive therapy: meta-analysis
      and meta-regression of randomized and controlled trials].
AB  - BACKGROUND: Meta-analysis is one of the most useful methodologies in evidence
      based medicine. The goal of this paper is to introduce meta-analysis and meta
      regression in the synthesis of scientific evidence in the efficacy of
      antihypertensive therapy. METHODS: Data from 13 randomized controlled trial
      comparing active antihypertensive therapy with a non-therapeutic control have
      been analyzed. Data on trials following patients at least more than one year have
      been poole through random-effects models and meta-regression models. RESULTS:
      Pooled data from meta-analysis showed that antihypertensive therapy decreased the
      risk of adverse outcomes attributable to the disease, mainly stroke. Regression
      models indicated that this risk was independent from study duration and patients
      mean age. CONCLUSIONS: The results of this study have showed the applicability
      and usefulness of data synthesis techniques in decision making in health care
      using hypertension as a case-study. This case-study allows us to make
      recommendations for research and therapy.

PMID- 10916804
TI  - [Effectiveness and cost of total hip replacement in seven hospitals in Catalonia,
      Spain].
AB  - BACKGROUND: To quantify short-term benefits of total hip replacement, prognostic
      factors of the outcome, and to assess hospital costs of this surgical procedure
      in Catalonia, Spain. PATIENTS AND METHODS: Multicentric prospective study in
      seven hospitals in Catalonia. All patients undergoing this procedure in one year
      were included. They were evaluated prior to the operation, and six months later.
      This evaluation involved: clinical assessment, the Hip Pain and Function Scale,
      the Nottingham Health Profile (NHP), and the EuroQol (EQ-5D), in order to measure
      cost-utility. Hospital costs were estimated by means of a specific questionnaire.
      RESULTS: Information was obtained for 332 patients. The mean age was 65 years
      (range: 27-89 years); 58% were women; the most common diagnosis was arthritis;
      59% of patients had associated pathology and 13% presented some type of
      postoperative complication. The improvement in health status was important
      according to all instruments. An outcome of "excellent" or "good" was achieved by
      70.8% of the patients, in terms of hip function and pain. The factors associated
      with not achieving an outcome of this level were: associated pathology,
      complications, diagnoses other than arthritis, and operation carried out in a
      tertiary hospital. The total cost of the procedure was 838,480 pesetas. This
      average varied significantly with the cost of the prosthesis, and as a function
      of the length of stay. The three-year cost-utility of the procedure was estimated
      as 507,500 pesetas. CONCLUSIONS: Total hip replacement greatly improves the pain,
      hip function and overall perceived health of the patient. This improvement is
      greater among patients with a diagnosis of arthritis, with good overall health,
      operated on by a surgeon experienced in this procedure. The benefit is high in
      relation to the cost, although there is a margin for improvement, reducing
      complications, shortening length of stay, and controlling the price of implants.

PMID- 10916805
TI  - [Efficacy and cost of ambulatory cataract surgery: a systemic review].
AB  - BACKGROUND: A systematic review has been performed on the literature in order to
      assess efficacy and costs of cataract ambulatory surgery. The objective of the
      review were the randomized controlled trials comparing benefits, adverse effects
      and costs of ambulatory and inpatient cataract surgery, including, in addition,
      an original trial of our investigation group. METHODS: The sources of information
      have been: MEDLINE (between 1985 and 1998), HealthStar (1975-98), Evidence-Based,
      the systematic review of the journals of ophthalmology (1992-98) and the review
      of the references in the documents or articles reviewed. The quality of the
      trials was assessed according to criteria proposed by the Evidence-Based Medicine
      Working Group. Data extracted from each study included: design, object
      population, setting, type of intervention and treatment, and follow-up period.
      Outcomes of ambulatory surgery were compared to those of inpatient surgery
      concerning to benefits (postoperative visual acuity), adverse effects (surgical
      complications) and costs of the surgery. RESULTS: From 44 studies satisfying
      inclusion criteria, only 5 randomized controlled trials and 10 observational
      studies had the necessary information to be included in the review. In all the
      studies postoperative visual acuity was similar between the two groups
      (inpatients and outpatients). In the quantitative synthesis of the trials
      included in the review, outpatients presented a higher rate of perioperatory (48
      hours after surgery) complications (OR = 1.4; IC 95%: 1.1-1.8) and of increase of
      intraocular pressure (OR = 2.3; IC 95%: 1.3-3.9). The ambulatory surgery costs
      were from a 15 to a 30% lower, depending on the study analyzed. CONCLUSIONS:
      Ambulatory cataract surgery patients present a benefit in visual acuity similar
      to inpatients. However, the higher risk of surgical complications among
      outpatients suggests the appropriateness of improving their immediate
      postoperative care. Even though some variability exists in the method to
      calculate costs, the results suggest that ambulatory surgery is the most
      efficient alternative.

PMID- 10916806
TI  - [Validity of clinical tests to confirm or to exclude the diagnosis of acute
      appendicitis].
AB  - AIMS: The clinical usefulness of the diagnostic tests (usually employed to
      diagnose an acute appendicitis in a group of patients in which this diagnosis is
      clinically highly suspected). PATIENTS AND METHODS: A cross sectional study was
      designed. The sample (n = 116) was randomly selected by term and specific days
      from the patients attending the Emergency Service at Elda General Hospital in a
      year period. The method used was is a validity study making 2 x 2 tables. We have
      cross matched the habitual routine tests with: a) the clinical outcome if the
      patient was not surgically treated, or b) the result of the biopsy for those
      operated. Being these the gold standard. The validity indexes studied were
      sensibility (S), specificity (E). The 95% confidence index of the CF were
      calculated. RESULTS: Acute appendicitis clinical suspicion was confirmed in 29.4%
      (IC 95%: 20.8-38). The best validity indexes were: a) kind of pain (S = 81.3; E =
      33.8); b) peritoneal inflammatory signs (S = 78.5%, E = 45.9%); c) presence of
      leucocytosis in blood exam (S = 100%, E = 54.5%), and d) a greater difference in
      axillary-rectum temperature (S = 13.6%, E = 96.6%). Only leucocytosis reached 0
      for PP- and CP-; the blood leucocytosis (PP+ = 47.8%, CP+ = 2.20) and the
      axillary-rectum temperature (PP+ = 60%, CP+ = 4.0) dissociation were the test
      with most valuable indexes. CONCLUSIONS: Clinical suspicion of acute appendicitis
      in a group of patients having a great probability of suffering it over estimates
      this diagnosis. The symptoms or signs routinely used in the diagnosis did not
      reach high validity indexes in these patients. They are a poor help to stress or
      reject the diagnosis of acute appendicitis. To be careful is the main tool the
      doctors have. Blood leucocytosis is the test that has the best agreement indexes
      of clinical usefulness and it has the best countence with the gold standard.

PMID- 10916807
TI  - [Depression and clinical practice guidelines: evidence or confusion. Study group
      on the prescription and psychotropic in primary care].
AB  - BACKGROUND: The need of designing clinical practice guidelines in the context of
      the evidence based medicine relates to different aspects concerning the
      characteristics of the clinical condition, the health care context, the
      utilization of health services, and the existing knowledge about the topic of
      study. The objective of this study was to review the guideline development method
      for managing depression in care and its implications in clinical practice.
      MATERIAL AND METHODS: Review and classification of scientific articles published
      between 1990 and 1997 about depression guidelines according to its method of
      development. RESULTS: Between 1990 and 1997, 2 clinical practice guidelines on
      the management of depression were published using systematic review, 3 guidelines
      were developed through unsystematic review, 4 guidelines were developed from
      experts' consensus, and 19 published articles reviewed the applicability of the
      existing guidelines in the primary health care sector. Different points of view
      about the use of these guidelines had been detected. CONCLUSIONS: In the context
      of the evidence-based medicine, one should take into account that the overall
      goal of guidelines development is to ensure its validity in different health care
      levels, as well as to gather professionals' acceptance of its use and
      applicability.

PMID- 10916809
TI  - Incidence, risk and evolution of ostheoporotic hip fractures in Spanish women
      using a Markov type model.
AB  - BACKGROUND: To estimate osteoporotic hip fracture incidence rates, by age and
      gender, and lifetime fracture risk of women of different age groups over 45 in
      Spain, and to determine the expected number of fractures and fracture-related
      person-years of functional impairment, as a basis for estimating the social costs
      of osteoporosis in Spain and the avoided costs of fractures in future cost
      effectiveness analyses. MATERIAL AND METHODS: The natural history of disease,
      recognized from fractures, is described using a Markov model and MonteCarlo
      simulations. Four cohorts of 10,000 women, each of a different age group, were
      simulated. Data were obtained from six hospitals of different size and
      geographical setting, to allow for differences in hospital service structure.
      Patients included were all new cases of hip fracture who were attended in those
      hospitals in 1995. Results are extrapolated to the Spanish population based on
      1991 census. RESULTS: We can predict in the group of women aged 50 an over in
      Spain 968,000 osteoporotic hip fractures during their remaining lifetime, with a
      total amount of 1,013,000 fractures. Some 135,000 will become functionally
      impaired due to the fractures, accounting for 1,177,000 person-years of
      functional impairment. CONCLUSIONS: The study provides a prototype for estimating
      avoided costs of fractures in future cost-effectiveness analyses.

PMID- 10916808
TI  - [Antisecretory drugs and prophylaxis of secondary gastrointestinal effects
      associated with the consumption of non steroid anti-inflammatory drugs].
AB  - BACKGROUND: To evaluate the available evidence on the efficacy of antisecretory
      drugs in the prevention of serious upper gastrointestinal adverse events
      associated with the use of nonsteroidal antiinflammatory drugs (NSAID). METHODS:
      All studies published and abstracted in the MEDLINE from 1970 to 1999 were
      reviewed. Only randomized, double-blind and placebo-controlled studies with a
      follow-up longer than 4 weeks were selected. The variables upper gastrointestinal
      complications, gastric ulcer, duodenal ulcer and side effects in both primary and
      secondary prophylaxis were analyzed by meta-analysis techniques. RESULTS: No
      studies were available regarding the effects of antisecretory drugs in the
      prevention of upper gastrointestinal bleeding associated with NSAID use. Ten
      studies were identified in the prevention of both gastric and duodenal ulcers.
      The effect of these agents was found to be especially useful in the prevention of
      duodenal ulcers, in secondary prophylaxis and in the long-term use of NSAID. The
      most consistent effect was seen with omeprazole for both duodenal ulcer
      prevention (OR [95% CI] = 0.12 [0.06-0.23]) and gastric ulcer prevention (OR =
      0.20 [0.13-0.31)]. However, H2-receptor, antagonists were not significantly
      associated with gastric ulcer prevention in all the scenarios analyzed.
      CONCLUSIONS: Prescription of antisecretory drugs are justified in the prevention
      of both gastric and duodenal ulcers in patients taking NSAID. The best benefit is
      achieved with omeprazole.

PMID- 10916810
TI  - [Outpatient care of upper gastrointestinal hemorrhage not related to portal
      hypertension].
AB  - BACKGROUND: The handling of upper gastrointestinal hemorrhage (UGH) usually
      includes the hospitalization of all patients, regardless of severity and
      prognosis. The aim of this paper is to assess the security of the outpatient
      control of some UGH, after their assessment in the hospital emergency room.
      PATIENTS AND METHODS: Prospective cohort of 533 patients who attended over 1994
      and 1995 hospital emergency room for an episode of UGH not linked to portal
      hypertension. After clinical and endoscopical assessment in the emergency
      department, 422 cases (79%) were admitted and 111 (21%) discharged for outpatient
      care. An analysis is presented of the characteristics of both groups, their
      clinical outcomes and a multivariate analysis to assess the factors associated
      with the decision to admit the patient. RESULTS: Outpatients were young, with
      less comorbidity and better haemodynamic status than hospitalized patients. Most
      of outpatient cases UGH was due to gastroduodenitis, oesophagitis and Mallory
      Weiss syndrome, as opposed to the greater importance of peptic ulcer in those
      admitted. All outpatients presented clean lesions or haematic remains. 25 (5.9%)
      hospitalized patients presented rebleeding, vs. only 1 (0.9%) outpatient (p <
      0.05). When more severity cases were excluded from hospital group, the
      differences were not significant. All cases with active bleeding, severe
      haemodynamic repercussion or without endoscopy were admitted. For the remainder,
      the decision to admit was associated with the presence of bleeding stigmata,
      haemodynamic repercussion, some causes of hemorrhage, older age, and urea levels.
      CONCLUSIONS: Although the scarce sample do not permit definitive conclusions,
      results guide towards that a substantial part of UGH not linked to portal
      hypertension may be monitored without hospitalizing the patient, thereby
      minimizing care costs and increasing the productive capacity of the hospital,
      without increasing risks for the patient.

PMID- 10916811
TI  - [Physiopathologic knowledge and clinical practice. A case of high dose
      chemotherapy in breast cancer].
AB  - Breast cancer is the major cause of death from cancer in women. This causes a
      great activity in oncological investigation in this field. During the 80s
      preclinical data and retrospective analysis suggested a dose-response
      relationship both for adjuvant treatment and metastatic disease. Technical
      advances in collection and administration of peripheral stem cells and the
      development of hematological growth factors permitted the use, in this and other
      diseases, of high dose chemotherapy, usually with hematological support. All
      these things produced the widespread use of this technique with the only
      scientific support of phase II studies usually performed in only one center and
      with highly selected patients. Most of the randomized trials performed afterwards
      did not show a clinically important relationship between dose and response. This
      makes us think that this technique should not be used as routinary treatment.
      From a methodological point of view it would be interesting to investigate the
      evolution of this modality of treatment and why, its use has been so generalized
      without good quality scientifically support. This could be due to predetermined
      ideas in relation to what is the evolution and treatment of this disease, the
      neglect in the use of scientific methodology and the pressures coming from
      different directions trying to adopt new (and presumably better, treatments). It
      is evident that if most of the patients who have received high dose treatment for
      breast cancer had participated in randomized trials the question would probably
      have already been answered.

PMID- 10916812
TI  - [Effect of alendronate on bone mineral density and incidence of fractures in
      postmenopausal women with osteoporosis. A meta-analysis of published studies].
AB  - BACKGROUND: To perform a systematic review, completed with a meta-analysis, of
      the published evidences about the effect of oral alendronate on bone mineral
      density and the incidence of fractures in postmenopausal women with low bone
      mass. METHODS: We search for all alendronate clinical trials in postmenopausal
      women with low bone mass which were randomized, double blind, placebo controlled,
      with a duration of one year or more and with bone mineral density measurement
      and/or fractures as outcomes. We used the weighted average of individual study
      results as an estimation of the global effect. RESULTS: Seven studies meet all
      the inclusion criteria. Relative Risks (RR) with 95% Confidence Intervals (CI
      95%) for the combined effect under fixed effects model were: RR 0.54 (CI 95%:
      0.45 to 0.66) for vertebral fractures, RR 0.81 (CI 95%: 0.72 to 0.92) for non
      vertebral fractures and RR 0.64 (CI 95%: 0.40 to 1.01) for hip fractures.
      CONCLUSIONS: Our results demonstrate that alendronate reduces the risk of
      vertebral, non vertebral and hip fractures in postmenopausal women with low bone
      mass. This meta-analysis allows the classification of alendronate anti-fracture
      evidences in the highest level.

PMID- 10916813
TI  - [Non-pharmacological medical interventions based on evidence. An exploratory
      study].
AB  - BACKGROUND: Non-pharmacological interventions prescribed are a frequent component
      of the medical practice mainly in ambulatory settings and also require a sound
      scientific basis. Our purpose was to estimate the proportion of evidence based
      non-pharmacological medical interventions in the clinical practice of an
      ambulatory setting. SUBJECTS AND METHODS: Medical interventions present in 150
      medical records were review from a systematic sample. The evidence for the
      interventions was searched in Medline (1986-1997). They were classified according
      the presence of supporting experimental evidence for each of the intervention.
      RESULTS: We found 92 different primary diagnosis. A 25% were non-pharmacological
      interventions and the rest mostly pharmacological. A 80% of the non
      pharmacological were evidence based. The most frequent non-pharmacological
      interventions were those related to cardiovascular disease (diet, physical
      exercise, etc.), followed by upper respiratory tract infections (hydration), low
      back pain (physical therapy, rest or both), constipation (diet, exercise) and
      gastro-enteritis (diet). Only hydration or the respiratory tract lacks
      experimental based evidence. CONCLUSIONS: There are experimental evidence for the
      non-pharmacological interventions revised, easily accessible but unevenly
      distributed and with effectiveness issues remaining controversial.

PMID- 10916814
TI  - [Preventive activities in primary health care: identifying the agreement among
      evidence-based guidelines].
AB  - BACKGROUND: The purpose of this article is to identify the agreement among
      evidence-based guidelines about recommendations on preventive activities in low
      risk adults. METHODS: For which we identified, from the 1996 US Task Force on
      Preventive Services Guide those preventives activities classified like A or B
      (recommendation in favour of provision) and like D or E (recommendation against
      provision), excepting those D and E recommendations based on descriptives studies
      or expert opinions. Both preventive activities aimed at pregnant women and
      children and those which are not applicable to our context were excluded.
      Selected preventive services were compared with the range of age, sex and
      periodicity in which agreement with the recommendations of American College of
      Physicians and Canadian Task Force on Preventive Services existed. RESULTS: We
      found the following agreements. Screening activities. In favour: screening for
      hypercholesterolemia, hypertension, breast cancer, colorectal cancer, uterine
      cervix cancer, rubella, visual and hearing impairment and problem drinking.
      Against: cancer of prostate, lung, bladder and thyroid, and asymptomatic
      bacteriuria. Counseling activities. In favour: smoking, motor-vehicles injuries,
      alcohol consumption, unintended pregnancy. Immunizations and quimioprophylaxis.
      In favour: Vaccines for influenza, tetanus-diphtheria, hepatitis B and measles
      mumps-rubella. Postexposure prophylaxis to hepatitis A, hepatitis B,
      meningococcal, rabies and tetanus. CONCLUSIONS: We see then, that a high degree
      in agreement among the main guidelines exists; about the preventive activities to
      perform in Primary Health Services, nevertheless we observed low fulfillment of
      certain preventive activities in Primary Health Services, different barriers for
      the accomplishment from these activities were described.

PMID- 10916815
TI  - [Clinical trials in bronchial asthma].
AB  - Most of the clinical trials with new drugs on the treatment of asthma are carried
      out in well selected patients who are not representative of a very clinically
      heterogeneous disease, with periodic controls differing from those normally
      undertake in the general practice and specialist consultations. The clinical
      trials are usually performed over very short periods of time while the normal
      pharmacologic treatment of asthma requires prolonged treatment. The external
      validity of these studies is unknown but it is probably not comparable to
      internal validity. To improve the quality of the clinical trials on asthma,
      studies should be carried out on patients representing the global population in
      conditions which are closer to those of the real world and during prolonged
      periods of time.

PMID- 10916816
TI  - [Benign prostatic hyperplasia and evidence based medicine: its approach in
      clinical practice].
AB  - The contribution of evidence based medicine (EBM) methodology to the clinical
      practice of symptomatic benign prostatic hyperplasia (BPH) patients may be very
      helpful. Otherwise its development is incipient. BPH is still a high prevalent
      and far-reaching clinicopathologic entity. In the last few years, new drug and
      surgical therapies have emerged that have significantly changed BPH clinical
      management. In this article, the elements that make feasible the application of
      EBM to the clinical management of BPH patients are reviewed, with the aim of
      making this relation part of the vast extension of EBM in the different medical
      specialties. This objective is an answer to the double interest, on one hand, in
      defining the importance of this new concept of medical practice and, on the other
      hand, in making clinical practice suitable for solving the queries of a disease
      with such a variable influence in patient's welfare and quality of life. We
      therefore conclude that application of EBM methodology to BPH management is
      relevant and necessary.

PMID- 10916817
TI  - [Searching for evidence. A compilation of useful resources for health technology
      assessment].
AB  - The spectacular growth in the produced volume of published scientific and
      technical information during the last years makes it difficult to discriminate
      and localize the information of greater quality. The parallel development of
      technologies for the fast handling of great volumes of single information has
      partially solved the problem of the access and use of the most advisable
      information. Health technology assessment tries to facilitate the decision making
      on the introduction, diffusion or use of health technologies, being based on the
      best evidences available. In order to improve the process of searching for
      evidences, needed in the process of health technology assessment, the Agency of
      Health Technology Assessment of the Institute of Salud Carlos III (AETS) made a
      compilation of information resources that can be useful for searching biomedical
      information in general. This article presents the above mentioned compilation
      along with the description of the process of elaboration and the criteria of
      selection applied.

PMID- 10916818
TI  - [Status epilepticus].

PMID- 10916819
TI  - [The difficulty of defining and classifying status epilepticus].
AB  - Status epilepticus (SE) can theoretically be described using a simple definition
      based on physiopathological mechanisms: any seizure of epileptic nature, partial
      or generalized, convulsive or non-convulsive, lasting over a period of more than
      30 minutes; or repeated seizures lasting for a period of over 30 minutes without
      recovery of consciousness. In the context of a historical review of various
      definitions, the validity of this definition is assessed and questioned. The
      heterogeneous nature of this condition is evidenced in daily clinical practice
      and by the results of epidemiologic studies. In the present study, the authors
      propose a more pragmatic and heuristic classification, taking into account not
      only clinical but also electroencephalographic data, as well as the particular
      nature of the epileptic syndrome when this is known.

PMID- 10916820
TI  - [Drug resistant status epilepticus].
AB  - Refractory epileptic state (RES) is defined by severe seizures that are resistant
      to antiepileptic drug treatment. Diagnostic errors such as pseudo-seizures and
      encephalopathies with triphasic waves must be distinguished at an early stage
      from cases of RES. The latter are symptomatic of a focal brain lesion or severe
      systemic disease, most frequently metabolic in origin. The treatment of such
      conditions is aimed at correction of the underlying cause. A nosographic issue
      that is still a subject of discussion and which requires further study, i.e.,
      PLEDS, will also be discussed in this article.

PMID- 10916821
TI  - [Status epilepticus with confusional symptomatology].
AB  - Non-convulsive confusional status epilepticus (NCSE) is classically separated
      into two forms on the basis of the ictal EEG, i.e., absence status (AS) and
      complex partial status epilepticus (CPSE). The diagnosis is difficult on the
      basis of clinical semiology alone, and requires emergency EEG investigation.
      Absence status, or 'petit mal' status, is a polymorphic condition that can
      complicate many epileptic syndromes, and is the most frequently encountered form
      of NCSE. It is characterized by confusion of varying intensity, associated in 50%
      of cases with bilateral periocular myoclonias. The EEG shows ictal generalized
      paroximal activity; normalization is obtained after benzodiazepine injection. In
      AS, there is a significant nosographic heterogeneity. Four groups can be
      distinguished: i) typical AS occurs in the context of a generalized idiopathic
      epilepsy; ii) atypical AS occurs in patients with symptomatic or cryptogenic
      generalized epilepsies; iii) 'de novo' AS (of late onset) is characterized by
      toxic or metabolic precipitating factors in middle-aged subjects with no previous
      history of epilepsy; iv) AS with focal characteristics occurs in subjects with a
      pre-existing or newly diagnosed partial epilepsy, mostly of extra-temporal
      origin. The majority of cases are in fact transitional forms between these four
      groups. CPSE is characterized by continuous or rapidly recurring complex partial
      seizures which may involve temporal and/or extratemporal regions. Cyclic
      disturbance of consciousness is characteristic of CPSE of temporal lobe origin,
      which requires vigorous treatment to prevent recurrence or cognitive sequelae.
      CPSE of frontal lobe origin is a diagnostic challenge: it is rare, the symptoms
      are unusual, and the patients should be documented extensively. A focal frontal
      lesion is revealed in one-third of cases.

PMID- 10916822
TI  - [Morbidity and mortality of status epilepticus].
AB  - The outcome of status epilepticus (SE) depends on its cause, clinical
      presentation, duration, treatment, and the patient's age. It has been estimated
      that in nearly all cases (about 98%), mortality is directly or indirectly due to
      the underlying disorder. It is particularly significant in generalized tonic
      clonic SE. The clinical presentation of SE is strongly cause-dependent, and its
      etiology is markedly age-dependent in infants, children, young adults and the
      elderly. When SE is of long duration, due to its etiology, delayed treatment, or
      inappropriate drug administration, it results in brain lesions and the
      accompanying risk of sequelae or death. The highest mortality rates in SE are
      those at the extremes of the average life-span, i.e., in infants and young
      children and in the elderly. Possible SE sequelae are neurologic deficits or
      cognitive impairment, and/or unprovoked seizures. The outcome in cases of SE has
      considerably improved due to the early prescription of effective antiepileptic
      drugs.

PMID- 10916823
TI  - [Neuropathologic consequences of status epilepticus].
AB  - Although the results of a number of histopathological studies have unequivocally
      shown that epileptic seizures are frequently associated with neurodegenerative
      mechanisms or other alterations in the brain structure, as it is not possible to
      carry out longitudinal studies the interpretation of these observations remains
      speculative. It is not clear whether these brain alterations are the cause or the
      result of epileptic seizures. It is now widely accepted that epileptic seizures
      correspond to the synchronization of neuronal activity and increase in their
      discharge frequency. It has been shown that this abnormal firing activity can
      lead to increase in intracellular calcium concentration in the nerve cells. A
      rise in intracellular calcium levels can trigger other processes within the cell,
      or be cytotoxic if these levels are sufficiently high. In this study, in the
      light of the most recent findings on cell death (apoptosis), the authors have
      examined the mechanisms whereby epileptic seizures can result in neuronal cell
      loss.

PMID- 10916824
TI  - [Treatment of status epilepticus in a developing country].
AB  - Status epilepticus (SE) is a condition requiring emergency care, which is often
      poorly managed in developing countries due to the lack of personnel, drugs, and
      insufficient technical and medical means. This study aims at determining the
      epidemiologic and etiologic characteristics and the difficulty in treating SE
      under the existing medical practice conditions in a developing country such as
      Senegal. A retrospective study was therefore carried out based on SE medical
      files at the University Hospital of Dakar over the period January 1988 to
      December 1998, and included several hospital departments, i.e., paediatrics,
      infectious diseases and neurology. Over an 11-year period 697 cases were
      recorded; of these, 48.2% of patients were under 5 years of age. The seizures
      were generalized in 58.2% of cases, partial in 21.2%, partial secondarily
      generalized, or with an association of both clinical presentations in 20.6% of
      cases. The etiology was as follows: mainly infectious (67%), followed by
      resistant and/or unbalanced epilepsy (9.9%), epilepsy of vascular origin (8%),
      and various other causes. The overall mortality rate was 24.8%. A long period
      between the onset of clinical symptoms and hospital treatment was noted, with an
      average time lapse of 16.6 h before treatment. The drugs utilized were diazepam
      and phenobarbitol, administered by injection. The overall outcome could be
      improved by better management, i.e., better prevention and an efficient treatment
      of infectious diseases, a reduction in the time before treatment, and improved
      means of intensive care.

PMID- 10916825
TI  - Syphilis treatment notes.

PMID- 10916826
TI  - Healthy People 2010 and protecting children.

PMID- 10916827
TI  - Interpreting the PPD: TB skin-testing of patients with previous BCG vaccination.

PMID- 10916828
TI  - New directions in heart failure management.
AB  - Approximately 4.8 million Americans are afflicted with heart failure; this
      accounts for 800,000 to 900,000 hospital admissions annually. Astute management
      in the primary care setting is essential for decreasing mortality and minimizing
      the risk for hospitalization. Although heart failure was initially viewed as a
      hemodynamic disorder, current evidence overwhelmingly supports that
      neurohormones, such as angiotensin II and aldosterone, contribute significantly
      to disease progression. The benefits of angiotensin-converting enzyme inhibitors
      and other drugs that block these substances are well established. This article
      discusses current management options that retard left ventricular remodeling to
      improve systolic function over time.

PMID- 10916829
TI  - Hodgkin's disease in primary care.
AB  - Hodgkin's disease is a common hematologic malignancy in young adults. The typical
      patient is a young adult male presenting with painless cervical adenopathy or a
      mediastinal mass on chest X-ray. If diagnosed early and aggressively treated,
      long-term survival rates are excellent. The subtypes of Hodgkin's disease are
      differentiated by pathologic examination of an affected lymph node. Chemotherapy,
      with or without adjuvant radiation, is the favored therapeutic regimen for most
      patients. A comprehensive approach to care, which incorporates psychosocial
      implications, can improve quality of life for Hodgkin's disease patients.

PMID- 10916830
TI  - Detecting hereditary hemochromatosis.
AB  - Hereditary hemochromatosis is the most commonly inherited autosomal recessive
      disorder. Hemochromatosis is a current or potential progression of abnormally
      high accumulations of iron in the liver. If left untreated, the condition can
      lead to chronic or irreversible hepatic fibrosis, cirrhosis, hepatocellular
      carcinoma, arthritis, and organ failure. Common signs and symptoms seen in the
      primary care setting include fatigue, weakness, abdominal pain, palpitations,
      skin pigmentation changes, and arthropathy, but any symptom associated with organ
      damage may be reported. Because prompt intervention can cease or reverse the
      debilitating effects of iron overload, prompt disease diagnosis and treatments
      are imperative.

PMID- 10916832
TI  - The Teratology Society 40th annual meeting, 24th NBTS annual meeting, 19th BTS
      annual meeting, 13th OTIS International Conference. Palm Beach, Florida, USA.
      June 24-29, 2000. Abstracts.

PMID- 10916831
TI  - Alosetron: a new therapy for irritable bowel syndrome.

PMID- 10916833
TI  - [The "problem" mare part 3: veterinary supervision at the stud and during early
      pregnancy].
AB  - In this last article the veterinary supervision of problem mares at the stud is
      reviewed. Treatment possibilities are evaluated. The usefulness of treatment with
      progestagens in order to sustain pregnancy or to prevent embryonic death is
      discussed.

PMID- 10916835
TI  - [Reaction on BVD article].

PMID- 10916834
TI  - [Hypocalcemia].

PMID- 10916836
TI  - [The "European College of Veterinary Surgery" (ECVS)].

PMID- 10916838
TI  - [Fetus delivery as a useful method].

PMID- 10916837
TI  - [Wishes of the milk industry, clinical mastitis and a case report].

PMID- 10916839
TI  - [Interesting disease cases in pigs from the past].

PMID- 10916840
TI  - [Geriatric peripheral vestibular ataxia].

PMID- 10916841
TI  - [A febrile myositis ... not very nice!].

PMID- 10916842
TI  - [The bomb was not only in the abdomen].

PMID- 10916843
TI  - [Shock? Stop!].

PMID- 10916844
TI  - ["Bovine endocarditis!"].

PMID- 10916845
TI  - [A "diagnosis of goldsmith"].

PMID- 10916846
TI  - [A diagnosis that deceives enormously].

PMID- 10916847
TI  - [A pleurisy that can speak of her].

PMID- 10916848
TI  - [A rugbyman and four bats].

PMID- 10916849
TI  - [The last voyage of a globe-trotter].

PMID- 10916850
TI  - [Hepatitis C with many complications...].

PMID- 10916851
TI  - [An infantile acidosis!].

PMID- 10916852
TI  - [Ascites and emaciation].

PMID- 10916853
TI  - Immunohistochemical study of the neuropeptides in the stellate ganglion of the
      water buffalo.
AB  - The localization of some neuropeptides including neuropeptide Y (NPY), substance
      P (SP), calcitonin gene related peptide (CGRP), vasoactive intestinal peptide
      (VIP), galanin (Gal), methionine enkephalin (M-ENK), tyrosine hydroxylase (TH)
      immunoreactivity was studied in the stellate ganglion (SG) of water buffalo. NPY,
      SP, Gal and TH immunoreactivities were present in almost all of the ganglion
      cells. NPY, SP, Gal, SP, CGRP, VIP and M-ENK immunoreactive nerve fibers were
      also seen in the SG. The localization and pattern of distribution of these
      peptides in the water buffalo stellate ganglion were compared with those in
      stellate ganglia of other mammalian species.

PMID- 10916854
TI  - Homology between Fas and nicotinic acetylcholine receptor protein in a thymoma
      with myasthenia gravis--immunohistochemical and biochemical study.
AB  - Nicotinic acetylcholine receptor (nAChR) protein and Fas were detected in a
      cortical type thymoma from a patient with myasthenia gravis (MG).
      Immunohistochemical study showed the presence of these two antigens in the
      neoplastic thymic epithelial cells. This was confirmed by immunoblot analysis of
      the thymoma extract using polyclonal anti-nAChR (FCT) antibody and two monoclonal
      anti-Fas antibodies. A homology search between each of five subunits of nAChR and
      Fas in sequences of nucleotides and amino acids were performed. In nucleotides
      the percent identity revealed 44.1 and 44.4 in the alpha and gamma subunits,
      respectively. The places of homology in amino acids sequences between nAChR and
      Fas were found in alpha 316-355 and Fas 232-271, gamma 321-352 and Fas 3-34.
      These portions with homology include previously reported T-cell epitopes, alpha
      320-337 and gamma 321-340. These two antigens may play a role in triggerring
      autoimmunity in MG.

PMID- 10916855
TI  - Kawasaki disease. Kawasaki disease?
AB  - Four cases of Kawasaki Disease (KD) treated at Bartlett Regional Hospital,
      Juneau, AK, are reviewed and discussed. Diagnostic and therapeutic measures
      recommended by the American Heart Association were followed and these cases
      discussed. Another case of probable Kawasaki Disease occurring in Anchorage,
      Alaska Native Medical Center, in 1965, is presented and compared with the other
      four. Current management of KD, with intravenous gamma globulin (IVGG) and
      aspirin (ASA) is highly effective, but was not known or available in 1965.

PMID- 10916856
TI  - Traumatic brain injuries in Alaska, 1996-1998.
AB  - Traumatic brain injuries often lead to severe disability or death. These injuries
      most often affect younger, more active people and are likely to have enduring
      physical, emotional, and financial costs. In order to determine the incidence,
      etiology and severity of traumatic brain injuries in Alaska, the Alaska
      Department of Health and Social Services has conducted a three-year study of the
      demographic and epidemiologic characteristics of traumatic brain injuries in
      Alaska. From 1996 through 1998, 1,932 hospitalized cases or out-of-hospital
      deaths occurred in the state among Alaska residents, for an average incidence
      rate of 105.2 per 100,000 population. To analyze the incidence of these injuries,
      the Traumatic Brain Injury Surveillance Project analyzed the location,
      demographics, and etiology.

PMID- 10916857
TI  - Social influences on Pap smear screening frequency.
AB  - Incidence and mortality rates of cervical cancer among Native American women is
      two to five times that of comparable Whites. Social and cultural differences
      contribute to this problem. We studied thirty age 40 and older American Indian
      women, half of whom had obtained at least one Pap in the past three years, the
      other half of whom had not. We asked: Do the two groups differ in their attitudes
      concerning Pap tests and those with whom they interact concerning Pap tests? and:
      Do they interact differently with different social groups concerning Pap tests?
      Data were obtained from chart audits and Given's Health Belief Questionnaire. The
      groups did not differ as to who they discussed Pap tests with or whose opinions
      they respected. They respected healthcare professionals most, family/friends
      less, and co-workers/others least. These findings suggest that the advanced
      practice nurse has an opportunity to improve Pap screening rates in this
      population.

PMID- 10916858
TI  - Every encounter is an opportunity for recommending breast and cervical cancer
      screening in women. Alaska Breast & Cervical Cancer Early Detection Program.

PMID- 10916859
TI  - The top ten reasons physicians are sued for malpractice.

PMID- 10916860
TI  - EENT field clinics, 1969.

PMID- 10916861
TI  - Multicultural minds. A dynamic constructivist approach to culture and cognition.
AB  - The authors present a new approach to culture and cognition, which focuses on the
      dynamics through which specific pieces of cultural knowledge (implicit theories)
      become operative in guiding the construction of meaning from a stimulus. Whether
      a construct comes to the fore in a perceiver's mind depends on the extent to
      which the construct is highly accessible (because of recent exposure). In a
      series of cognitive priming experiments, the authors simulated the experience of
      bicultural individuals (people who have internalized two cultures) of switching
      between different cultural frames in response to culturally laden symbols. The
      authors discuss how this dynamic, constructivist approach illuminates (a) when
      cultural constructs are potent drivers of behavior and (b) how bicultural
      individuals may control the cognitive effects of culture.

PMID- 10916862
TI  - A science of meaning. Can behaviorism bring meaning to psychological science?
AB  - An argument is presented for making meaning a central dependent variable in
      psychological science. Principles of operant psychology are then interpreted as
      providing a basic foundation for a science of meaning. The emphasis here is on
      the generality of basic operant concepts, where learning is a process of meaning
      making that is governed largely by natural contingencies; reinforcement is an
      organic process in which environment-behavior relations are selected, defined
      here as a dialectical process of meaning making; and reinforcers are experiential
      consequences with acquired, ecologically derived meanings. The author concludes
      with a call for a more interdisciplinary science of psychology, focusing on the
      individual in society.

PMID- 10916863
TI  - Responses to nervous breakdowns in America over a 40-year period. Mental health
      policy implications.
AB  - The 1957 and 1976 Americans View Their Mental Health surveys from the Institute
      of Social Research were partially replicated in the 1996 General Social Survey
      (GSS) to examine the policy implications of people's responses to feeling an
      impending nervous breakdown. Questions about problems in modern living were added
      to the GSS to provide a profile of the public's view of mental health problems.
      Results were compared for 1957, 1976, and 1996. In 1957, 19% of respondents had
      experienced an impending nervous breakdown; in 1996, 26% had had this experience.
      Between 1957 and 1996, participants increased their use of informal social
      supports, decreased their use of physicians, and increased their use of
      nonmedical mental health professionals. These findings support policies that
      strengthen informal support seeking and access to effective psychosocial
      treatments rather than current mental health reimbursement practices, which
      emphasize the role of primary care physicians.

PMID- 10916864
TI  - Issues in comparative psychology at the dawn of the 20th century.
AB  - Comparative psychology emerged as part of the "new psychology" that took hold in
      the United States around 1900. Many of the issues that have occupied comparative
      psychologists throughout the 20th century were developed as research problems
      during this period. In some respects, comparative psychology was then an integral
      and widely respected part of psychology at large; in others, it was already
      marginalized. Issues emerging during this critical period set the program for the
      upcoming century and included those of methodology in the conduct of experiments
      and conceptual issues related to evolution, development, intelligence, and higher
      processes.

PMID- 10916865
TI  - Practicing school psychology. A turn-of-the-century perspective.
AB  - Contemporary school psychology is more than an extrapolation of its early
      circumstances. However, several aspects remain intact despite changes in child
      classification, technology and instrumentation, regulation, and
      professionalization of the field. A snapshot is presented of school psychology
      practice during its origin period at the turn of the 20th century.

PMID- 10916866
TI  - Antidepressants are not placebos.

PMID- 10916867
TI  - Free will: an automatic response.

PMID- 10916869
TI  - Automaticity and the myth of personal agency.

PMID- 10916868
TI  - Automaticity, goals, and environmental interactions.

PMID- 10916870
TI  - The automaticity of interpreting automaticity.

PMID- 10916871
TI  - Automatic assumptions of automaticity.

PMID- 10916872
TI  - Some problems with Humean causality.

PMID- 10916873
TI  - Lectinhistochemical and cytometrical evaluation of the corpus luteum of the rat
      at the end of pregnancy.
AB  - Most studies on the biochemistry and structure of the corpus luteum have focused
      on elucidating the processes of progesterone synthesis and release. In the
      present work, the histochemical composition of the corpus luteum of the rat was
      evaluated using lectinhistochemistry on rats at the end of pregnancy (days 18
      23). We also analysed the morphology of the luteal cells, to characterize the
      changes attributable to regression in this organ. Seven biotinylated lectins were
      used (CON-A, WGA, DBA, SBA, PNA, RCA and UEA-I) following pre-set protocols (ABC
      method). The average diameter and area of the cells and their nuclei were
      measured. High reactivity of the luteal cells was observed with CON-A and a lower
      reactivity with WGA. The capillary endothelium gave positive reactivity with WGA
      and to a certain extent with SBA, PNA and RCA. Vesicular structures were
      intensely stained with DBA, and were more abundant in sections from animals with
      more advanced pregnancy, which could be attributable to cellular debris, on the
      basis of their morphologic characteristics. There were no significant differences
      among the cytometric variables analysed in comparisons of the values
      corresponding to the different days of gestation. These observations, together
      with previous research, suggest that, on the day of delivery, the corpus luteum
      of the rat is in the very early stages of structural regression, with no changes
      at the morphological level, but with changes at the molecular level.

PMID- 10916874
TI  - Fine structure of the retinal pigment epithelium, Bruch's membrane and
      choriocapillaris in the horse.
AB  - The fine structure of the retinal pigment epithelium (RPE), Bruch's membrane and
      choriocapillaris was investigated by light and transmission electron microscopy
      in both the tapetal and non-tapetal fundus of the horse eye. In all locations,
      the RPE consisted of a single layer of low cuboidal cells. The epithelial cells
      were joined laterally by apically located tight junctions. These cells displayed
      numerous basal infoldings and abundant thin apical processes which enclosed the
      rod outer segments. The epithelial cell nuclei were large and located basally.
      Within the epithelial cells, smooth endoplasmic reticulum was very abundant,
      while rough endoplasmic reticulum was scarce, polysomes and mitochondria, which
      often display a ring-shaped structure, were abundant. Melanosomes were abundant
      in the non-tapetal area but absent in the tapetal area. Bruch's membrane was
      pentalaminate throughout the retina. The endothelium of the choriocapillaris was
      heavily fenestrated.

PMID- 10916875
TI  - Comparison of localization of the neurokinin 1 receptor and nitric oxide synthase
      with calbindin D labelling in the rat spinal cord.
AB  - A comparison of the localization of the neurokinin 1 (NK1) receptor and nitric
      oxide synthase with calbindin D labelling in the lumbar spinal cord was carried
      out in the rat using immunocytochemistry. Considerable regional variations were
      observed. Application of the antibody to calbindin D resulted in dense staining
      in laminae I and II and light staining in the other laminae. Occasional scattered
      cells were seen in the deep laminae and in the lamina X, the ventral horn and the
      lateral spinal nucleus. The results indicate that neurones expressing calbindin
      D, NK1 receptor and NOS are three separate populations in the dorsal horn of the
      lumbar spinal cord.

PMID- 10916876
TI  - A quantitative study of the aorta of the New Zealand rabbit (Oryctolagus
      cuniculus L.).
AB  - Ten segments of the aorta of the rabbit were studied quantitatively. The thoracic
      and abdominal aorta of the rabbit were measured from proximal to distal and
      parallel to the reduced diameter, demonstrating a decreasing thickness of the
      tunica intima and tunica media that becomes physiologically apparent during
      adulthood in these commonly used laboratory animals. The ratio of intimal to
      medial thickness, multiplied by 100, was calculated and found to be between 2.56
      and 3.74 for the thoracic aorta and 4.03 and 5.62 for the abdominal aorta of the
      rabbit. These findings are important for the better understanding of the
      development of atherosclerosis.

PMID- 10916877
TI  - A scanning electron microscopic study of the peritoneal mesothelium covering the
      genital tract and its ligaments in the cow.
AB  - This study was undertaken to describe the surface features of the peritoneal
      mesothelium covering the genital tract and adjacent ligaments of the cow during
      the oestrous cycle. The relationship between mesothelial surface and spermatozoa
      was also evaluated after intra-uterine and intraperitoneal insemination. Surface
      features of mesothelial cells from 25 cyclic cows were examined by scanning
      electron microscopy and by image analysis. Presence of spermatozoa was evaluated
      by scanning electron microscopy in seven additional cows. In the external side of
      the infundibulum, the oviductal mucosa exceeds the free margin, forming a
      continuous band measuring 2.5-10 mm in width. This oviductal epithelium shows
      cyclical variations with a predominance of ciliated cells during the follicular
      phase. In respect of the mesothelium, no clear morphological differences were
      observed associated with the side of ovarian bursa (internal versus external), or
      with the phase of the oestrous cycle. Mesothelial cells covering the uterus and
      mesometrium have a higher microvilli density and length and a smaller cell
      surface area than in the oviduct and adjacent structures. The presence of
      solitary cilia in the mesosalpinx and mesotubarium superius (infundibulo-cornual
      ligament) of some specimens was also observed. When samples were processed
      without postfixation in osmium tetroxide, a layer of amorphous material covered
      all surfaces. After intra-uterine insemination of five cows, no spermatozoa were
      found on their peritoneal mesothelium. Numerous spermatozoa were found after
      intraperitoneal insemination being attached throughout mesothelial surfaces.
      These results indicate that there are morphological differences between regions,
      but no cyclic changes, in the surface features of mesothelial cells covering the
      genital tract and adjacent ligaments of the cow, and that spermatozoa can bind to
      mesothelial surfaces after intraperitoneal insemination.

PMID- 10916878
TI  - [Principles of construction in the fore- and hindpaw of the domestic cat (Felis
      catus). 2. Articulations].
AB  - According to form and range of mobility the joints of the cat's paw
      (articulationes manus et pedis) are adjusted to two basic functions: as far as
      they are used for walking in the different gaits they show components in the
      sagittal plane that particularly correspond to the digitigrade dog. With regard
      to cat-specific behaviour, i.e. climbing and catching, specific characteristics
      of the joints for movements in the R-plane (rotation) and A-plane
      (abduction/adduction) can be distinguished. For this reason highly specialized
      types of articulations occur in cat's paw that are unique compared to other
      mammals and that mostly have not been described yet. In this context, like in the
      skeleton (see first communication), function-adapted divergences can also be
      found between the joints of the forepaw and hindpaw of the cat.

PMID- 10916879
TI  - Immunohistochemical localization of neuropeptides in bovine pancreas.
AB  - The occurrence and density of distribution of nerves and endocrine cells that are
      immunoreactive for neuropeptides in the bovine pancreas were studied by
      immunohistochemistry. The six neuropeptides localized were galanin (GAL),
      substance P (SP), methionine-enkephalin (MENK), neuropeptide Y (NPY), calcitonin
      gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP). The
      exocrine pancreas was shown to have an appreciable number of GAL- and SP
      immunoreactive nerve fibres but few fibres showing immunoreactivity for VIP and
      CGRP. Numerous MENK-, GAL-, SP-, and NPY-immunoreactive nerve fibres were seen in
      the endocrine portion of the pancreas. Nerve cell bodies in the intrapancreatic
      ganglia showed immunoreactivity for all of the neuropeptides except CGRP.
      Endocrine cells showing immunoreactivity for GAL and SP were observed in the
      large islets and islets of Langerhans, respectively. The present results indicate
      a characteristic distribution of neuropeptides in the bovine pancreas, which may
      regulate both exocrine and endocrine secretions of pancreas.

PMID- 10916880
TI  - Immunohistochemical study on the distribution of endocrine cells in the
      gastrointestinal tract of the babirusa, Babyrousa babyrussa (Suidae).
AB  - The distribution and relative frequency of endocrine cells in the
      gastrointestinal tract of the babirusa were studied immunohistochemically using
      the avidin-biotin-peroxidase complex method. Thirteen types of gut endocrine
      cells were detected; they were immunoreactive for chromogranin, serotonin,
      somatostatin, gastrin, bovine pancreatic polypeptide (BPP), glucagon, secretin,
      cholecystokinin (CCK), methionine-enkephalin-Arg6-Gly7-Leu8 (MENK8), motilin,
      gastric inhibitory polypeptide (GIP) and peptide tyrosine tyrosine (PYY). Cells
      that were immunoreactive for chromogranin, serotonin, somatostatin and glucagon
      were found in all portions of the gastrointestinal tract. MENK8-immunoreactive
      cells were observed in the stomach and small intestine. Gastrin-immunoreactive
      cells were detected in the pyloric region and duodenum. PYY-immunoreactive cells
      were found in the small and large intestine. Cells immunoreactive for motilin,
      CCK, GIP, and secretin were observed in the proximal small intestine and those
      immunoreactive for neurotensin were found only in the ileum. Although the
      distribution pattern of endocrine cells in the gastrointestinal tract of babirusa
      was similar to those reported for pig, restricted distribution of several
      endocrine cells, gastrin, BPP, MENK8, motilin, CCK, GIP, secretin and neurotensin
      and wider distribution of glucagon and PYY were observed in the babirusa. The
      unexpected presence of MENK8 in all glandular regions of the stomach and PYY in
      the small intestine was also noted. The distribution of gut endocrine cells might
      be related to the regulatory characteristics of the babirusa digestive tract.

PMID- 10916881
TI  - Aspects of the functional morphology of the ductus epididymidis in domestic
      anseriform and galliform birds.
AB  - The structure of the ductus epididymidis, and its capacity to take up luminal
      particulate material (India ink) were studied, using scanning and transmission
      electron microscopy, in the domestic fowl, turkey and Japanese quail (Order
      Galliformes) and drake (Order Anseriformes). The epithelium appeared contractile
      and stable structurally, especially in the drake in which, among other
      cytoskeletal features, abundant perinuclear intermediate filaments radiated
      peripherally in the principal, nonciliated (Type III) cell. The Golgi complex was
      well developed, except in the turkey in which it was extremely inconspicuous.
      Sparsely granulated profiles were the main component of the elaborate endoplasmic
      reticulum, which was best developed in the drake and least in the turkey. The
      cell in the turkey was uniquely laden with large aggregates of lipid droplets.
      Generally, characteristics of a cell active in the synthesis and merocrine
      secretion of proteinaceous material were evident. There was no evidence of
      apocrine-like secretion in well-fixed tissues. The cell lacked the capacity to
      take up luminal India ink particles, and displayed very poorly developed
      endocytic structural features, which are also probably only selectively and
      minimally absorptive. Ultrastructural features varied between and within the
      orders studied, necessitating further studies.

PMID- 10916882
TI  - [The role of mast cells in cutaneous allergic diseases and mast cell
      proliferation and differentiation in skin].

PMID- 10916883
TI  - [Current insight of adolescent asthma--from pediatrics].

PMID- 10916884
TI  - [A relationship between a psychosomatic and a skin condition in patients with
      atopic dermatitis].
AB  - Atopic dermatitis (AD) has been clinically well-known to be frequently
      exacerbated by some psychosomatic stress. In this study, we examined a
      relationship between a psychosomatic and a skin condition in patients with AD.
      Visual analogue scale (VAS) for the grade of general physical condition, mental
      stress and others were reported daily for themselves, while skin physiological
      parameters, resident skin bacteria and a psychological questionnaire (POMS) were
      measured every 2 weeks. It was observed that tense-anxious and depressive scores
      of POMS tended to correlate with skin conductance, a skin clinical score and a
      number of total skin bacteria and others. These results suggest that changes of
      psychosomatic condition reciprocally correlate with the exacerbation and
      improvement of skin symptom in patients with AD.

PMID- 10916885
TI  - [Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis].
AB  - Eighteen cases (7 males and 11 females) of food-dependent exercise-induced
      anaphylaxis were observed for several years. The age of the patients at the first
      visit to our hospital ranged from 9 to 43 years (average 24.3 years). The
      offending foods were wheat in 9 cases, shrimp in 2 cases, shellfish in 1 case,
      fish in 1 case, and unknown foods in 5 cases. The inducing exercises were ball
      play games, running, riding a bicycle, swimming, kendo (Japanese fencing),
      walking, and so on. We advised these patients to avoid eating offending foods or
      taking exercises, or to take antiallergic medicine such as DSCG, and repirinast.
      We observed their clinical courses and laboratory data for 2 to 10 years. Only a
      few cases relapsed anaphylactoid reactions, but all cases have improved until
      now. In some cases, IgE RAST scores for wheat decreased. In other cases, the rate
      of histamine release on anti-IgE stimulation decreased after taking DSCG.

PMID- 10916886
TI  - [Clinical characteristics of seafood allergy and classification of 10 seafood
      allergens by cluster analysis].
AB  - The aim of this study was to investigate the clinical characteristics of children
      who showed sensitization to any type of seafood and to classify the 10 seafood
      allergens based on IgE reactivities by a cluster analysis. In children with
      bronchial asthma (BA) and/or atopic dermatitis (AD), we defined the 'seafood'
      group as 23 patients having any type of seafood specific IgE antibody (CAP
      system). We analyzed the clinical features, the serum total IgE and each allergen
      specific IgE level. In addition, ten seafood allergens were also classified by a
      cluster analysis. Three patients revealed immediate hypersensitivity to some
      seafood. The frequency of patients with AD and the total IgE in the seafood group
      were high and the patients in this group were tend to be sensitized to multiple
      allergens. Seafood allergens were classified into 4 groups, 1) salmon, sardine,
      horse mackerel and mackerel, 2) cod and tuna, 3) octopus and squid, and 4) crab
      and shrimp, by a cluster analysis. These findings corresponded to the biological
      classification and the classification by the reported common allergens among
      various types of seafood. Based on our findings, this classification is therefore
      considered to be useful when selecting allergens to screen for sensitization to
      seafood.

PMID- 10916887
TI  - [A case of atopic dermatitis which showed correlation of psychological state and
      lesions--changes of value of psychological test, skin lesion and NK cell
      activity].
AB  - The relationship between psychological state and skin lesions of atopic
      dermatitis were investigated with a 31-year-old male patient. He had severe
      atopic dermatitis which became worse with psychological stress. A psychological
      test, profile of mood states (POMS), was performed on him every 2 weeks.
      Peripheral lymphocytes and natural killer (NK) cell activity were investigated at
      some points. When the psychological state showed more depressive, anxiety, anger,
      fatigue and confusion, the skin lesions became worse and recovered after the
      psychological states turned well. Correlation was shown between itch and stress
      or fatigue by a visual analogue scale (VAS) (p < 0.001). NK cell activity
      decreased during the worse psychological state and recovered during the near
      normal psychological state, although, the lymphocyte count and CD4/8 ratio in
      peripheral blood did not change during the study. These results suggest that some
      patients with atopic dermatitis should be treated psychologically in addition to
      standard dermatological treatment.

PMID- 10916888
TI  - [The countermeasure to pollinosis by a web site of Internet].
AB  - For the countermeasure to pollinosis, we opened "the web site of pollinosis by
      allergic group of otorhinolaryngology, Jikei Medical School" and provided the
      information of pollinosis for patients in the web site of internet from the
      spring of 1997. In the web site we kept to be informed of the pollen forecast,
      daily dispersed pollens, and medical information being renewed frequently of
      prevention and therapy for pollinosis. For the principle of therapy, we adopted
      the guideline for allergic rhinitis which was produced by Japan Allergic
      Societies and recommended visitors to get standard therapy for pollinosis.
      Consequently, the web site was accessed up to 160,000 times by the summer of 1999
      and we received 204 medical questions by e-mail and answered to these all mails.
      We then made a questionnaire study after 3 each pollen seasons and received over
      200 answers which showed that our fresh information was useful to decrease
      symptoms of pollinosis. These results show that information by web site seems to
      be useful for the countermeasure to pollinosis and will be more important to
      support medical treatment in hospitals in future.

PMID- 10916889
TI  - [Asthma death among adults in Japan 1995-1997. Analysis of 295 cases reported
      questionnaires sent to hospitals with more than 100 beds. Asthma Death
      Investigation Committee].
AB  - To clarify recent trends in adult asthma mortality, the Asthma Death
      Investigation Committee of Japan studied the clinical characteristics of 295
      patients who died of asthma between 1995 and 1997. Males were slightly more than
      females among the death cases. Approximately half of the patients ranged in age
      from 60 to 79 years. Tendency to increase of death among young male adults
      continued. One third of the patient deaths involved the asphyxic type, while
      status asthmaticus was the cause death in 21.9%. Half of the asthmatics died in
      hospitals or emergency rooms, and places where the fatal attacks occurred were
      mainly patients' houses. The main cause fatal asthma attacks was respiratory
      infection, followed by fatigue, stress, and discontinuation of medication. Most
      of the patients were classified moderate or severe type of asthma 1 month before
      death. Histories of life-threatening attacks and hospitalization due to severe
      attacks, irregular visits to the hospital, low compliance, and insufficiency of
      corticosteroid treatment were suggested as the main risk factors in adult asthma
      deaths.

PMID- 10916890
TI  - [Churg-Strauss syndrome during corticosteroid tapering in a patient with
      bronchial asthma receiving pranlukast].

PMID- 10916891
TI  - [Do existing family and community medicine teaching units have to disappear?].

PMID- 10916892
TI  - [Do family and community medicine teaching units have to evolve?].

PMID- 10916893
TI  - [Treatment compliance in arterial hypertension. A 2-year intervention trial
      through health education].
AB  - OBJECTIVE: To analyse the efficacy of health education (HE) through a group
      session with two years of intervention by postal back-up on compliance with
      therapy for light-to-moderate essential hypertension. DESIGN: Controlled,
      randomised clinical trial. SETTING: La Orden Health Centre. PARTICIPANTS: 110
      hypertense patients diagnosed with de novo or unmonitored hypertension.
      INTERVENTION: 1. Control group (CG): 55 patients who received HE from their
      doctor. 2. Intervention group (IG): 55 patients who also received a controlled
      intervention. a) Group HE session, b) Postal back-up to the home every three
      months for two years. MEASUREMENTS AND RESULTS: After two years, on two surprise
      home visits made at a month's interval, blood pressure was measured and pressure
      lowering pills counted. The person whose consumption was at 80-110% of the amount
      prescribed was defined as compliant. The percentages of compliant patients and
      mean compliance were compared for the two visits. The reduction of absolute risk
      (RAR), of relative risk (RRR) and the number of patients needed to avoid non
      compliance (NNT) were calculated. 92 people finished the trial. The two groups
      (n: CG = 45, IG = 47) did not differ for age, sex, time of evolution, number of
      illnesses or dosages of medicines prescribed. 78.26% were compliant (CI: 61.5
      94.9), CG = 55.6% and IG = 95.7% (p < 0.0001). Mean overall compliance was 90.9
      +/- 14, CG = 88.1 +/- 12 and IG = 93.86 +/- 11 (p = 0.01). RAR was 40.1%, RRR
      90.3 and NNT 2.49% respectively. CONCLUSIONS: HE intervention is an effective
      measure to improve therapeutic compliance in essential hypertension and lasts for
      up to two years.

PMID- 10916894
TI  - [Go to the health center or go to the drug store? Pharmacy offices as a primary
      care resource].
AB  - OBJECTIVE: To find what the pharmacy office represents socially to the population
      that uses it most. DESIGN: Qualitative study. Analysis of the contents of two
      discussion groups. PARTICIPANTS: Women from 30 to 60 years old, urban residents
      of the Community of Madrid. MEASUREMENTS AND MAIN RESULTS: The pharmacy offices
      were identified by the user as a primary care resource which was accessible--both
      because of its closeness and opening hours--and trustworthy. They provided health
      care support for treating minor ailments ("assisted self-medication") and also
      advised on medical technicalities and use of medication. Users with potentially
      serious clinical pictures were referred from the pharmacy to the doctor. The
      images associated with "going to the doctor" lacked the nearness and familiarity
      of "dropping round to the pharmacy". CONCLUSIONS: Integrating pharmacy office
      pharmacists into a general primary care framework would improve the health of the
      general population.

PMID- 10916895
TI  - [Impact of a pharmacotherapy bulletin at a primary health care area].
AB  - OBJECTIVE: To evaluate the impact of the recommendations in the bulletin of
      pharmacotherapeutic information on the prescription of iron salts by the area's
      doctors. DESIGN: Intervention study with control group. SETTING: Two primary care
      areas in Asturias. PARTICIPANTS: Intervention group: 93 doctors from area 3.
      CONTROL GROUP: 59 doctors from area 7. INTERVENTIONS: In March 97 an informative
      bulletin was issued recommending the use of ferrous salts rather than ferric
      salts and was sent to all area 3's doctors. MEASUREMENTS AND MAIN RESULTS: The
      PFe2 indicator was calculated: defined daily dose percentage of ferrous salts out
      of total iron salts in three time periods: January-March '97 (t1), April-June '97
      (t2) and January-March '98 (t3). In the intervention group, the PFe2 value
      increased progressively in the three periods. There were significant differences
      between t1 and t3 (mean increase: 6.0%, 95% CI: 1.9%-10.1%, p = 0.004) and
      between t2 and t3 (mean increase: 4.5%, 95% CI 0.8%-8.3%, p = 0.017), whereas the
      differences were not significant between t1 and t2 (mean increase 1.5%, 95 CI
      1.3%-4.2%, p = 0.296). The respective values for the controls only showed
      significant differences for variation in periods t2 and t3 (mean increase: 2.0%,
      95% CI 0.2%-3.8%, p = 0.017). CONCLUSIONS: 1. The bulletin issued in the area had
      a favourable impact. 2. This impact could only be seen in the medium term, not in
      the short term.

PMID- 10916896
TI  - [What are Gypsies like and what do they suffer from?].
AB  - OBJECTIVE: To find and compare the social and demographic features and health
      status of two different ethnic and cultural groups, gypsies and payos (non
      gypsies). DESIGN: Observational, descriptive, crossover study. SETTING: Primary
      care. PARTICIPANTS: The 121 gypsy patients > 14 registered at the centre and 121
      controls who were matched for age. INTERVENTIONS: Social and demographic
      variables, risk factors, chronic illnesses and involvement in preventive and
      health promotion programmes were gathered. MEASUREMENTS AND MAIN RESULTS: On the
      basis of a questionnaire that was filled out with data from the primary care
      health histories, we saw that there were significant differences in educational
      background, jobs and work situation (p < 0.0005). Among the gypsies there were
      more alcohol consumers, intravenous drug users and patients at social-health
      risk. Hb, Hc and HIV affected gypsies significantly more (the two groups were
      included in preventive programmes and activities). Mean age of death among
      gypsies was early (40.6 years vs. 73). Paradoxically, gypsies used private
      medicine more. CONCLUSIONS: There were significant social-health differences
      between the two groups studied. The gypsies on our health centre lists need
      greater care from the primary care team, so that they can achieve better health
      status.

PMID- 10916897
TI  - [Clinical features of respiratory tuberculosis and diagnosis delay].
AB  - OBJECTIVE: To make a descriptive analysis of the clinical characteristics of
      patients with pulmonary tuberculosis and find the time of diagnostic delay.
      DESIGN: Retrospective study. SETTING: Autonomous Community of Navarre. PATIENTS:
      317 cases of pulmonary tuberculosis diagnosed between January 1 1993 and June 30
      1996. RESULTS: The most commonly observed symptom was coughing (76.8%), followed
      by expectoration (63.8%) and high temperature (60.3%). The high percentages of
      high temperature, asthenia, anorexia and weight loss in HIV-infected patients
      stood out. The mean period of diagnostic delay was 36.9 to 58.5 days, with a
      median of 15 days. For 76.8% of patients the delay in diagnosis was under a
      month. CONCLUSIONS: Early diagnosis is essential in tuberculosis control,
      especially in cases transmitted by bacilli, since these are highly contagious for
      months.

PMID- 10916898
TI  - [Assessment of ophthalmologic control of the diabetic patient in primary care].
AB  - OBJECTIVE: To evaluate ophthalmic control in patients with diabetes mellitus (DM)
      in primary care (PC). DESIGN: Crossover observation study. SETTING: Hellin Health
      Centre (Albacete). PATIENTS: 137 diabetics selected at random, excluding pregnant
      women and children under 14. MEASUREMENTS AND MAIN RESULTS: The variables of age,
      sex, type of diabetes (DM1/DM2), years of evolution, ophthalmic control and
      appearance of diabetic retinopathy (DR) were studied. Mean age was 68.5 +/- 10.9
      years. 52% were women (n = 72). 88% had DM2 (n = 121). Time of evolution from
      diagnosis was < 5 years in 46% (n = 63), 6-10 years in 23% (n = 32), 11-15 years
      in 14% (n = 19), > 15 years in 5% (n = 7) and nothing was recorded for 12% (n =
      16). 41% (n = 56) of the patients had not had an ophthalmic evaluation. Of the
      59% (n = 81) referred to the ophthalmology out-clinic (OOC), 65 patients followed
      recommendations of the Spanish Society of Retina and Vitreous Humour, and 16 were
      referred for other reasons, of which cataracts was the most common eye pathology.
      Of these 81 patients referred to the OOC, 29% did not have DR (n = 23), and 44%
      did (n = 36). Of this 44%, 14 were light, 15 moderate, 3 severe and 4
      proliferating cases. The reports were not sent back to PC in 27% of cases (n =
      22). CONCLUSIONS: Ophthalmic referral in PC is still deficient for a large number
      of DM patients. DR of varying degrees was detected in a high number of cases who
      did have an ophthalmic check-up. Communication between PC and ophthalmic care
      concerning diabetic patients must improve.

PMID- 10916899
TI  - [Evaluation of dental caries in 6-year old students in the Manresa basic area
      (Barcelona)].
AB  - OBJECTIVE: To find the state of buccal-dental health of the 6-year old population
      attending the schools belonging to Manresa area 4. DESIGN: Four crossover,
      observational, epidemiological studies performed over the last 4 years (1995
      1999). SETTING: Health Area 4, Sagrada Familia, in the city of Manresa,
      Barcelona. PARTICIPANTS: 489 students doing the first year of primary school in
      the schools belonging to Manresa area 4 from 1995-1999. MEASUREMENTS AND MAIN
      RESULTS: There was 29.81% prevalence of caries (31.88% in boys and 27.85% in
      girls). The COD index (deciduous dentition) was 1.075 (1.25 in boys and 0.90 in
      girls) and the CAOD index (permanent dentition) was 0.115 (0.127 in boys and
      0.104 in girls). CONCLUSIONS: Results showed low indices of caries if we compare
      them with the WHO Health programme target for the year 2000 of restricting caries
      to under 50% of six-year old children. However, this is below target 46 in the
      Catalonia Health Plan, which set for the year 2000 a target of 75% of six-year
      old school-children free of caries.

PMID- 10916900
TI  - [Prevention of cervix cancer. Comparison of the sample quality obtained using
      cotton swab or cervical brush].
AB  - OBJECTIVE: To determine the pap smear adequacy, and to compare the quality using
      cervical cytobrush with that obtain by using cotton swab in the endocervical
      sample. DESIGN: Transversal study. Carried out in two periods both pre and post
      intervention. SETTING: Primary care centre in the south of Madrid. INTERVENTION:
      We have analysed all the pap smear performed during two periods. In the first
      period we obtained 1130 smears using cotton swab and 884 smears using cervical
      cytobrush in the second period. We used the Ayre Spatula to obtain the
      exocervical samples. RESULTS: 2014 pap smears were analysed. Of the 1130 smears
      examined in the primary study using the cotton swab, 25.9% were inadequate
      because of the absence of the transformation zone cells. In the second group, 884
      pap smears obtained by using the cytobrush, only 13.9% were reported as
      inadequate smears, p < 0.00001 (chi square). 18 smears were positive for
      malignancy (6 suspicious, 9 CIN I, 3 CIN III, all under the age of 49. 14.6% were
      positive for infections. There were no significant differences in the smear
      adequacy in regards to the professional who obtained the sample. CONCLUSIONS: We
      have improved the smear adequacy 12% by using the cytobrush. We recommend the
      cytobrush for endocervical smears to avoid having to repeat the sample. We
      consider it necessary to indicate the smear adequacy in all pathology reports.

PMID- 10916901
TI  - [Factors associated with the occurrence of adverse reactions to drugs in patients
      who went to the emergency service of a general hospital: a case-control study].
AB  - OBJECTIVE: To describe adverse reactions to medicine (ARM) and analyse the
      factors associated with their presenting in patients attending a general
      hospital's emergency service. DESIGN: Case-control epidemiological study.
      SETTING: Emergency service of the San Cecilio University Hospital in Granada.
      PATIENTS: 654 patients over 15, men and women, who attended the emergency service
      between October and December 1997. 354 of them had an ARM (cases) and 300 did not
      (controls). MEASUREMENTS AND RESULTS: 60% of the cases were women, with an
      average age of 53 +/- 20. 68% of the ARM were type-A (expected). The most
      affected organs and systems were: digestive tract (41.8%) and skin (31.6%). Drug
      groups most associated with presentation of ARM were hypnosedatives and
      salicylates used as analgesics--antithermic drugs (28.2%), and beta-lactams and
      macrolides (22.6%). Most ARM were classified as probable (52%) and moderate
      (62%). Family practitioners were the main prescribers (49%) of medicines. 13% of
      patients were admitted to hospital because of a serious ARM and two people died
      (0.5%). According to the odds ratio, treatment with cytostatics, psychiatric
      drugs, NSAIDs, amoxycillin, digoxin, ACEIs and calcium antagonists, being a
      woman, self-medication, being under 65 and history of ARM were all associated
      with the presence of an ARM in our patients (cases). CONCLUSIONS: The type of
      medicine, being a woman, history of ARM, self-medication, and presenting
      digestive and dermatological symptoms were factors strongly linked to an ARM in
      patients attending the emergency service.

PMID- 10916902
TI  - [Incidence of dental caries in a child population from Mostoles: evaluation of a
      preventive program after 2 years].
AB  - OBJECTIVE: To know the efficacy and effectivity od dental health program after 2
      years. DESIGN: The study of prospective cohorts not aleatorized. POPULATION AND
      METHODS: The exposed cohort is composed of 583 school children, 296 girls and 287
      boys, the non-exposed cohort is composed of 261 school children, 132 girls and
      129 boys. We carried out and odontological exploration following the criteria of
      the WHO the preventive measures we carried out are health education, weekly
      mouthrinse of NaFl at 0.2%, occlusive sealant in the first permanent molar and
      external application fluorine gel. We measured and compared the different indexes
      of tooth decay and sociodemographic variables between both cohorts, the statistic
      meaning has been determined through the U est of Mann Whitney. RESULTS: We have
      found statistically significant differences between both cohorts in the indexes
      of decay in the exposed cohorts. The indexes of decay in the exposed cohort being
      DMFT: 0.31; DMFM (first permanent molar): 0.31; DMFS: 0.4. And in the non-exposed
      cohort DMFT: 0.81; DMFM: 0.81; DMFS; 1.09. Existing an epidemiological
      association between the preventive program and the prevention of dental decay
      with a relative risk of 0.24 (95% CI, 0.17-0.33) and the prevention fraction of
      76.3% (95% CI, 67-83). CONCLUSIONS: The preventive program after two years
      elapsed is effective and has a clear protector effect.

PMID- 10916903
TI  - [Health promotion project "Promoting the health adaptation in our adolescents"].

PMID- 10916904
TI  - [Therapeutic approach to humor in palliative care].

PMID- 10916905
TI  - ["Antibiotic culture" of the population].

PMID- 10916907
TI  - [Therapeutic evaluation focused on... the drug].

PMID- 10916906
TI  - [Urinary tract infections in primary care].

PMID- 10916908
TI  - Health systems: more evidence, more debate.

PMID- 10916909
TI  - A framework for assessing the performance of health systems.
AB  - Health systems vary widely in performance, and countries with similar levels of
      income, education and health expenditure differ in their ability to attain key
      health goals. This paper proposes a framework to advance the understanding of
      health system performance. A first step is to define the boundaries of the health
      system, based on the concept of health action. Health action is defined as any
      set of activities whose primary intent is to improve or maintain health. Within
      these boundaries, the concept of performance is centred around three fundamental
      goals: improving health, enhancing responsiveness to the expectations of the
      population, and assuring fairness of financial contribution. Improving health
      means both increasing the average health status and reducing health inequalities.
      Responsiveness includes two major components: (a) respect for persons (including
      dignity, confidentiality and autonomy of individuals and families to decide about
      their own health); and (b) client orientation (including prompt attention, access
      to social support networks during care, quality of basic amenities and choice of
      provider). Fairness of financial contribution means that every household pays a
      fair share of the total health bill for a country (which may mean that very poor
      households pay nothing at all). This implies that everyone is protected from
      financial risks due to health care. The measurement of performance relates goal
      attainment to the resources available. Variation in performance is a function of
      the way in which the health system organizes four key functions: stewardship (a
      broader concept than regulation); financing (including revenue collection, fund
      pooling and purchasing); service provision (for personal and non-personal health
      services); and resource generation (including personnel, facilities and
      knowledge). By investigating these four functions and how they combine, it is
      possible not only to understand the proximate determinants of health system
      performance, but also to contemplate major policy challenges.

PMID- 10916910
TI  - The concept of stewardship in health policy.
AB  - There is widespread agreement that both the configuration and the application of
      state authority in the health sector should be realigned in the interest of
      achieving agreed policy objectives. The desired outcome is frequently
      characterized as a search for good governance serving the public interest. The
      present paper examines the proposal in The World Health Report 2000 that the
      concept of stewardship offers the appropriate basis for reconfiguration. We trace
      the development of stewardship from its initial religious formulation to more
      recent ecological and sociological permutations. Consideration is given to the
      potential of stewardship for encouraging state decision-making that is both
      normatively based and economically efficient. Various dilemmas that could impede
      or preclude such a shift in state behaviour are examined. We conclude that the
      concept of stewardship holds substantial promise if adequately developed and
      effectively implemented.

PMID- 10916911
TI  - Benchmarks of fairness for health care reform: a policy tool for developing
      countries.
AB  - Teams of collaborators from Colombia, Mexico, Pakistan, and Thailand have adapted
      a policy tool originally developed for evaluating health insurance reforms in the
      United States into "benchmarks of fairness" for assessing health system reform in
      developing countries. We describe briefly the history of the benchmark approach,
      the tool itself, and the uses to which it may be put. Fairness is a wide term
      that includes exposure to risk factors, access to all forms of care, and to
      financing. It also includes efficiency of management and resource allocation,
      accountability, and patient and provider autonomy. The benchmarks standardize the
      criteria for fairness. Reforms are then evaluated by scoring according to the
      degree to which they improve the situation, i.e. on a scale of -5 to 5, with zero
      representing the status quo. The object is to promote discussion about fairness
      across the disciplinary divisions that keep policy analysts and the public from
      understanding how trade-offs between different effects of reforms can affect the
      overall fairness of the reform. The benchmarks can be used at both national and
      provincial or district levels, and we describe plans for such uses in the
      collaborating sites. A striking feature of the adaptation process is that there
      was wide agreement on this ethical framework among the collaborating sites
      despite their large historical, political and cultural differences.

PMID- 10916912
TI  - Challenges for health systems in member countries of the Organisation for
      Economic Co-operation and Development.
AB  - For reasons of equity most OECD countries have chosen to base their funding of
      health care mainly on public sources. There is an almost universal problem of
      affordability in the health systems of these countries, arising from the tension
      between the willingness of populations to pay taxes and the eagerness of patients
      to use health services where these are free or heavily subsidized at the point of
      use. These tensions are likely to be exacerbated by a surge of new medical
      technologies adding to demands for health care. Some observers have predicted the
      breakdown of publicly funded systems of health care under new spending pressures.
      However, governments can deploy a range of policies for handling new demands.
      They can also take comfort from the fact that many of them have already coped
      with successive waves of technological change in health care without abandoning
      their core commitment to the public funding of health systems. Furthermore, if
      standards of living continue to rise, public and private insurers should find it
      easier to obtain the revenues needed to pay for the improved health care expected
      by consumers.

PMID- 10916913
TI  - Benchmarks for health expenditures, services and outcomes in Africa during the
      1990s.
AB  - There is limited information on national health expenditures, services, and
      outcomes in African countries during the 1990s. We intend to make statistical
      information available for national level comparisons. National level data were
      collected from numerous international databases, and supplemented by national
      household surveys and World Bank expenditure reviews. The results were tabulated
      and analysed in an exploratory fashion to provide benchmarks for groupings of
      African countries and individual country comparison. There is wide variation in
      scale and outcome of health care spending between African countries, with poorer
      countries tending to do worse than wealthier ones. From 1990-96, the median
      annual per capita government expenditure on health was nearly US$ 6, but averaged
      US$ 3 in the lowest-income countries, compared to US$ 72 in middle-income
      countries. Similar trends were found for health services and outcomes. Results
      from individual countries (particularly Ethiopia, Ghana, Cote d'Ivoire and Gabon)
      are used to indicate how the data can be used to identify areas of improvement in
      health system performance. Serious gaps in data, particularly concerning private
      sector delivery and financing, health service utilization, equity and efficiency
      measures, hinder more effective health management. Nonetheless, the data are
      useful for providing benchmarks for performance and for crudely identifying
      problem areas in health systems for individual countries.

PMID- 10916914
TI  - International comparison of health care systems using resource profiles.
AB  - The most frequently used bases for comparing international health care resources
      are health care expenditures, measured either as a fraction of gross domestic
      product (GDP) or per capita. There are several possible reasons for this,
      including the widespread availability of historic expenditure figures; the
      attractiveness of collapsing resource data into a common unit of measurement; and
      the present focus among OECD member countries and other governments on containing
      health care costs. Despite important criticisms of this method, relatively few
      alternatives have been used in practice. A simple framework for comparing data
      underlying health care systems is presented in this article. It distinguishes
      measures of real resources, for example human resources, medicines and medical
      equipment, from measures of financial resources such as expenditures. Measures of
      real resources are further subdivided according to whether their factor prices
      are determined primarily in national or global markets. The approach is
      illustrated using a simple analysis of health care resource profiles for Denmark,
      France, Germany, Sweden, the United Kingdom, and the USA. Comparisons based on
      measures of both real resources and expenditures can be more useful than
      conventional comparisons of expenditures alone and can lead to important insights
      for the future management of health care systems.

PMID- 10916915
TI  - "Make or buy" decisions in the production of health care goods and services: new
      insights from institutional economics and organizational theory.
AB  - A central theme of recent health care reforms has been a redefinition of the
      roles of the state and private providers. With a view to helping governments to
      arrive at more rational "make or buy" decisions on health care goods and
      services, we propose a conceptual framework in which a combination of
      institutional economics and organizational theory is used to examine the core
      production activities in the health sector. Empirical evidence from actual
      production modalities is also taken into consideration. We conclude that most
      inputs for the health sector, with the exception of human resources and
      knowledge, can be efficiently produced by and bought from the private sector. In
      the health services of low-income countries most dispersed production forms, e.g.
      ambulatory care, are already provided by the private sector (non-profit and for
      profit). These valuable resources are often ignored by the public sector. The
      problems of measurability and contestability associated with expensive, complex
      and concentrated production forms such as hospital care require a stronger
      regulatory environment and skilled contracting mechanisms before governments can
      rely on obtaining these services from the private sector. Subsidiary activities
      within the production process can often be unbundled and outsourced.

PMID- 10916916
TI  - Organization of ambulatory care provision: a critical determinant of health
      system performance in developing countries.
AB  - Success in the provision of ambulatory personal health services, i.e. providing
      individuals with treatment for acute illness and preventive health care on an
      ambulatory basis, is the most significant contributor to the health care system's
      performance in most developing countries. Ambulatory personal health care has the
      potential to contribute the largest immediate gains in health status in
      populations, especially for the poor. At present, such health care accounts for
      the largest share of the total health expenditure in most lower income countries.
      It frequently comprises the largest share of the financial burden on households
      associated with health care consumption, which is typically regressively
      distributed. The "organization" of ambulatory personal health services is a
      critical determinant of the health system's performance which, at present, is
      poorly understood and insufficiently considered in policies and programmes for
      reforming health care systems. This article begins with a brief analysis of the
      importance of ambulatory care in the overall health system performance and this
      is followed by a summary of the inadequate global data on ambulatory care
      organization. It then defines the concept of "macro organization of health care"
      at a system level. Outlined also is a framework for analysing the organization of
      health care services and the major pathways through which the organization of
      ambulatory personal health care services can affect system performance. Examples
      of recent policy interventions to influence primary care organization--both
      government and nongovernmental providers and market structure--are reviewed. It
      is argued that the characteristics of health care markets in developing countries
      and of most primary care goods result in relatively diverse and competitive
      environments for ambulatory care services, compared with other types of health
      care. Therefore, governments will be required to use a variety of approaches
      beyond direct public provision of services to improve performance. To do this
      wisely, much better information on ambulatory care organization is needed, as
      well as more experience with diverse approaches to improve performance.

PMID- 10916917
TI  - The role of the hospital in a changing environment.
AB  - Hospitals pose many challenges to those undertaking reform of health care
      systems. This paper examines the evolving role of the hospital within the health
      care system in industrialized countries and explores the evidence on which policy
      makers might base their decisions. It begins by tracing the evolving concept of
      the hospital, concluding that hospitals must continue to evolve in response to
      factors such as changing health care needs and emerging technologies. The size
      and distribution of hospitals are matters for ongoing debate. This paper
      concludes that evidence in favour of concentrating hospital facilities, whether
      as a means of enhancing effectiveness or efficiency, is less robust than is often
      assumed. Noting that care provided in hospitals is often less than satisfactory,
      this paper summarizes the evidence underlying three reform strategies: (i)
      behavioural interventions such as quality assurance programmes; (ii) changing
      organizational culture; and (iii) the use of financial incentives. Isolated
      behavioural interventions have a limited impact, but are more effective when
      combined. Financial incentives are blunt instruments that must be monitored.
      Organizational culture, which has previously received relatively little
      attention, appears to be an important determinant of quality of care and is
      threatened by ill-considered policies intended to 're-engineer' hospital
      services. Overall, evidence on the effectiveness of policies relating to
      hospitals is limited and this paper indicates where such evidence can be found.

PMID- 10916918
TI  - What can we learn from international comparisons of health systems and health
      system reform?
AB  - Most commonly, lessons derived from comparisons of international health sector
      reform can only be generalized in a limited way to similar countries. However,
      there is little guidance as to what constitutes "similarity" in this respect. We
      propose that a framework for assessing similarity could be derived from the
      performance of individual policies in different contexts, and from the cause and
      effect processes related to the policies. We demonstrate this process by
      considering research evidence in the "public-private mix", and propose variables
      for an initial framework that we believe determine private involvement in the
      public health sector. The most influential model of public leadership places the
      private role in a contracting framework. Research in countries that have adopted
      this model suggests an additional list of variables to add to the framework. The
      variables can be grouped under the headings "demand factors", "supply factors",
      and "strength of the public sector". These illustrate the nature of a framework
      that could emerge, and which would help countries aiming to learn from
      international experience.

PMID- 10916919
TI  - The use of private-sector contracts for primary health care: theory, evidence and
      lessons for low-income and middle-income countries.
AB  - Contracts for the delivery of public services are promoted as a means of
      harnessing the resources of the private sector and making publicly funded
      services more accountable, transparent and efficient. This is also argued for
      health reforms in many low- and middle-income countries, where reform packages
      often promote the use of contracts despite the comparatively weaker capacity of
      markets and governments to manage them. This review highlights theories and
      evidence relating to contracts for primary health care services and examines
      their implications for contractual relationships in low- and middle-income
      countries.

PMID- 10916920
TI  - Managed care: the US experience.
AB  - This article provides an overview of managed health care in the USA--what has
      been achieved and what has not--and some lessons for policy-makers in other parts
      of the world. Although the backlash by consumers and providers makes the future
      of managed care in the USA uncertain, the evidence shows that it has had a
      positive effect on stemming the rate of growth of health care spending, without a
      negative effect on quality. More importantly, it has spawned innovative
      technologies that are not dependent on the US market environment, but can be
      applied in public and private systems globally. Active purchasing tools that
      incorporate disease management programmes, performance measurement report cards,
      and alignment of incentives between purchasers and providers respond to key
      issues facing health care reform in many countries. Selective adoption of these
      tools may be even more relevant in single payer systems than in the fragmented,
      voluntary US insurance market where they can be applied more systematically with
      lower transaction costs and where their effects can be measured more precisely.

PMID- 10916921
TI  - Health insurance: the influence of the Beveridge Report.

PMID- 10916923
TI  - Inequalities in health.

PMID- 10916922
TI  - Social insurance and allied services. 1942.

PMID- 10916924
TI  - Myths of community-based health care.

PMID- 10916925
TI  - Reliability of the clinical surveillance criteria for measles diagnosis.

PMID- 10916926
TI  - Companies reduce prices for HIV drugs in developing countries.

PMID- 10916927
TI  - New resolution on HIV/AIDS announced at the 53rd World Health Assembly.

PMID- 10916928
TI  - [Neuronal ceroid lipofuscinosis. Closing chapter of a long story].
AB  - Neuronal ceroid lipofuscinoses represent a group of diseases which has until
      quite recently resisted definite elucidation of the underlying defect(s) on the
      molecular level. The common feature of all the NCLs is a serious and progressive
      neurological disorder, accompanied, with only few exceptions, by retinal
      degeneration. Visceral symptoms, despite the presence of the storage process, are
      absent, or minimal. There are many clinical variants of the disease process,
      among which a set of standard, historical phenotypes exists found to be linked to
      specific genotypes. The disorder is inherited and transmitted as an autosomal
      recessive trait. At the cellular level, it is featured by lyzosomal storage of
      autofluorescent hydrophobic material, the substantial part of which consists of
      hydrophobic proteins and esterified dolichol. The dominant protein is the subunit
      c of mitochondria ATP synthase. In one NCL type (NCL1) the dominant proteins are
      saposins A and D. Ultrastructural appearance is membranous with several
      relatively specific patterns with some tendency to condensation or, namely in
      NCL3 to vacuolar distension. Amorphous appearance is associated with NCL1. The
      impact of the disease process on the cell biology differs substantially depending
      on the cell type. The brain neurons are most seriously affected and degenerate,
      whereas other cell types mostly survive without detectable deterioration.
      Pathogenesis at the molecular level is now being elucidated using the modern
      molecular biology techniques, which have already enabled unravelling of a set of
      genes controlling majority of the standard historical phenotypes. The original
      infantile form of NCL (NCL1) is now defined as palmitoyl protein thioesterase
      deficiency (gen at the 1p32 locus), the late infantile form (NCL2) as pepstatin
      resistant proteinase deficiency (gen at the 11p15.5 locus) and the original
      juvenile form (NCL3) as a defect of the specific gene (locus 16p11.2-12.3), the
      product of which, the NCL3 protein, still lacks functional characterization. Two
      gene loci have been identified in the so-called early juvenile, or variant late
      infantile NCL. One of them is in the 13q21 locus (NCL5 or Finnish variant late
      infantile form), the second is in the 15q21-23 one (NCL6). Kufs form remains the
      least defined form of NCL. Recently two novel NCL variants were described with
      specific loci. Thanks to introduction of molecular genetic based diagnosis it was
      possible to recognize, besides the standard phenotype, existence of further
      phenotypic variants. The phenotype based scheme of NCL has thus been definitely
      substituted by classification based on genotype and biochemistry.

PMID- 10916929
TI  - Atypical oxyphilic metaplasia of the uterine cervix. Report of a case.
AB  - A new example of atypical oxyphilic metaplasia (AOM) of the uterine endocervix
      occurring in a 37-year-old female is presented. This rare lesion is worrisome in
      appearance but entirely indolent and needs to be distinguished from glandular
      atypia or adenocarcinoma in situ of the cervix. In the present case, there were
      seen transitions between AOM and tubal metaplasia in some cervical glands.
      Additionally, similar eosinophilic and ciliated changes were found in the
      endometrium. These findings suggest that AOM, tubal metaplasia of the cervix and
      eosinophilic metaplasia of the endometrium may be related from the pathogenetic
      viewpoint.

PMID- 10916930
TI  - [Diagnosis of malacoplakia in a transplanted kidney by needle biopsy].
AB  - Malakoplakia is an uncommon inflammatory condition rarely involving parenchyma of
      transplanted kidney. We report a 44-year-old female recipient of a cadaveric
      renal allograft treated with cyclosporin A and prednisone. After transplantation,
      E. coli and Citrobacter bacteruria occurred and three years later decreased graft
      function developed. Percutaneous needle biopsy was performed and diagnosis of
      malakoplakia was established. Histologically, interstitial sheets of plasmocytes
      and histiocytes with periodic acid-Shiff positive cytoplasm containing Michaelis
      Gutmann bodies were present. Ultrastructurally, phagolysosomes containing
      membrane fragments and various developmental stages of inclusions to fully
      developed Michaelis-Gutmann bodies were found. The patient was treated with co
      piperacillin and subsequently pefloxacin and renal functions improved after six
      months follow-up. Our case suggests that malakoplakia represents an abnormal
      defective histiocytic response to the infection in the setting of
      immunosuppressive therapy.

PMID- 10916931
TI  - [Angiogenesis in tumors. Part II. Methods and significance of quantification;
      angiogenesis as a prognostic indicator and the target of therapeutic approaches].
AB  - The efforts to quantify tumor angiogenesis (AG) have been limited by the methods
      available. Only since introduction of immunohistochemistry, detection of early
      stages of capillary vessel formation is enabled. There were reports showing
      strong correlation between AG and behavior of the tumor (namely formation of
      metastases, disease free interval, and overall survival) particularly in
      carcinomas of the breast, prostate, esophagus, stomach and colon. However,
      significance of these studies is strongly dependent on the methodological
      aspects, e.g. the choice of visualized endothelial antigen, microscopic
      magnification and selection of areas with highest angiogenic activity (so called
      "hot spots"). We present a review of studies focused on AG and discuss pitfalls,
      which could bias the results. Current clinical applications as well as
      perspectives of future antiangiogenic treatment are also discussed.

PMID- 10916932
TI  - [Immunohistochemical methods in the differential diagnosis of primary traumatic
      and subsequent secondary cerebral changes].
AB  - In a 22-year-old man, driver of a personal motor vehicle, who died within 39
      hours after a traffic injury, the authors made histological and
      immunohistochemical examinations of the brain focused on differentiation of
      primary traumatic and subsequent secondary changes. In haematomas the authors
      revealed the presence bi- and trivalent iron by Turnbull's and Perl's reaction as
      well as glycophorin by immunohistochemical reactions. White matter lesions were
      evaluated histologically by staining according to Palmgren and
      immunohistochemically by detection of neuron-specific enolase, beta-amyloid
      protein precursor and low molecular neurofilaments. Minor contusion foci in the
      corpus callosum and in the peripheral portion of the pons revealed the presence
      of extracellular bivalent iron and exceptionally also the presence of
      intracellular iron. Glycophorin was present not only in erythrocyte membranes but
      also in the form of lumps signalizing haemolysis. In the haematoma in the median
      portion of the pons neither iron nor free glycophorin were detected. At all
      investigated sites (subcortical areas of the white matter of the hemispheres,
      capsula interna, corpus callosum, pons Varolii) the authors detected numerous
      axonal deformities (oedema or formation of retraction spheroids) which revealed
      on immunohistochemical examination an intense reaction with antibodies in
      particular against neuron-specific enolase and beta-amyloid protein precursor,
      and to a smaller extent against low-molecular neurofilaments. The combination of
      the mentioned immunohistochemical examinations seemed a suitable method for
      differentiating primary cerebral injury (diffuse axonal injury and minor
      contusion foci in the corpus callosum and the margin of the pons) from secondary
      changes (haemorrhages in the median portion of the pons) which developed shortly
      before death as a manifestation of haemodynamic disorders associated with
      cerebral oedema).

PMID- 10916933
TI  - [Glycophorin in forensic medicine].
AB  - Immunohistological evidence of glycophorin from paraffin sections of tissues
      fixed with formol, makes its possible to visualize membranes of preserved
      erythrocytes and fragments after their disintegration. This fact permits even
      after development of post-mortem changes to differentiate actual extravasation,
      manifested by a positive finding of glycophorin from mere infiltration of tissue
      by blood pigment after death, where glycophorin is lacking. The method is very
      sensitive and can reveal even very discrete haemorrhage. From different grades of
      erythrocyte disintegration in haematomas in the same subject sometimes
      conclusions can be drawn also on the different time of development of traumatic
      tissue changes.

PMID- 10916934
TI  - [Determination of amphetamine and methamphetamine in human hair using gas
      chromatography/mass spectrometry].
AB  - The authors present a procedure of concurrent identification and quantification
      of amphetamine and metamphetamine in human hair. The method involves rinsing of
      the hair (distilled water 55 degrees C, 0.1 M hydrochloric acid, distilled water
      to neutral reaction, methanol) drying in air, homogenization by cutting (1-2 mm
      long), alkaline hydrolysis (20 mg hair, 1 ml 1 M sodium hydroxide, 55 degrees C,
      120 min.), neutralization with 1 M hydrochloric acid to pH = 7, extracting
      benzoylation with 2,3,4,5,6-pentafluorobenzoyl chloride (0.3 ml 1 M sodium
      hydroxide, 4 ml cyclohexane, 30 ul cyclohexylamine in cyclohexane of a
      concentration of 20 ng/ul--internal standard, 50 ul aqueous solution of
      triethylamine hydrochloride concentration of 100 mg/ml--reaction catalyst and 10
      ul of derivation agent 2,3,4,5,6-pentafluorobenzoyl chloride dilution 1:10,
      shaking for 5 mins. by hand and leaving to stand for 10 mins.), centrifugation (5
      mins., 3000 rotations/min.), collection of 2 ml cyclohexane layer, its
      evaporation at 40 degrees C in nitrogen atmosphere and dilution with 100 ul
      cyclohexane. The derivated extract was subjected to analysis by the GC-MS method.
      The procedure was used for segmentation analysis of hair of two subjects abusing
      metamphetamine for prolonged periods. The revealed concentrations varied within
      the range of 0.99-5.25 mg/kg metamphetamine and 0.13-0.73 mg/kg amphetamine.

PMID- 10916935
TI  - [Surveying a zoological facility through satellite-based geodesy].
AB  - In the course of a thesis submitted for a diploma degree within the
      Fachhochschule Oldenburg the Serengeti Safaripark was surveyed in autumn and
      winter 1996/97 laying in the planning foundations for the application for
      licences from the controlling authorities. Taking into consideration the special
      way of keeping animals in the Serengeti Safaripark (game ranching, spacious walk
      through-facilities) the intention was to employ the outstanding satellite based
      geodesy. This technology relies on special aerials receiving signals from 24
      satellites which circle around the globe. These data are being gathered and
      examined. This examination produces the exact position of this aerial in a system
      of coordinates which allows depicting this point on a map. This procedure was
      used stationary (from a strictly defined point) as well as in the movement (in a
      moving car). Additionally conventional procedures were used when the satellite
      based geodesy came to its limits. Finally a detailed map of the Serengeti
      Safaripark was created which shows the position and size of stables and
      enclosures as well as wood and water areas and the sectors of the leisure park.
      Furthermore the established areas of the enclosures together with an already
      existing animal databank have flown into an information system with the help of
      which the stock of animals can be managed enclosure-orientated.

PMID- 10916936
TI  - [Effect of progesterone on the immune system in consideration of bovine placental
      retention].
AB  - Effects of progesterone on the immune system of different species are presented
      by a literature study. Elevated progesterone concentrations in blood result in
      more severe course and longer persistence of bacteria in infectious diseases and
      decrease of the clearance of antibody-coated erythrocytes in vivo. Progesterone
      suppresses specific components of the immune system and natural killer (NK) cell
      activity while it has a mainly positive influence on other nonspecific
      components. It suppresses blastogenesis and cytotoxicity of lymphocytes and
      increases synthesis of asymmetric antibodies without effector function to block
      fetal antigens. Progesterone increases the concentration of leucocytes in blood,
      random migration and chemotactic ability, synthesis of reactive oxygen
      intermediates (ROI) and antibody-dependent cellular cytotoxicity of
      polymorphonuclear leucocytes (PMN) and expression of complement receptors,
      synthesis of ROI and phagocytosis of peritoneal macrophages. In the uterus mainly
      immunosuppressive effects of progesterone are described (decreased migration of
      PMN into the gravid uterus, persistence of bacteria or transplants, synthesis of
      immunosuppressive uterine milk proteins, decreased random migration of PMN)
      except for an increased content of IgA in the secretory products indicating a
      significance of progesterone in the pathogenesis of endometritis mainly in the
      cow and bitch. No correlation could be found between blood concentrations of
      progesterone and placental retention in cattle. Progesterone takes part in
      avoiding immunologic aggression of the maternal organism against the
      semiallogenic conceptus by suppressing specific components of the immune system
      and NK cell activity. Positive effects on nonspecific components of the immune
      system could be regarded as compensatory mechanisms to maintain the efficiency of
      the complete immune system.

PMID- 10916937
TI  - [Comparison of various examination methods used in ovarian diagnostics in
      cattle].
AB  - In this study diagnostic certainty of ultrasonography and rectal palpation
      concerning the detection of follicles and C.I. was compared by evaluation of the
      findings obtained with ultrasonography in waterbath and dissection of the ovaries
      after slaughter. Clinical examinations were performed on a total of 30 cows
      (transrectally and ultrasonographically, 5.0 mhz, linear) in slaughterhouse. In
      the laboratory ovaries were evaluated after slaughter both macroscopically and by
      ultrasonography in waterbath. Diagnostic reliabilities of these methods were
      compared. No difference between the methods was determined concerning the
      longitudinal measurements of corpora lutea (19.96 +/- 4.83 mm, 20.41 +/- 5.41 mm,
      21.45 +/- 5.26 mm by ultrasonography, waterbath and macroscopy respectively). By
      means of determining the correct identification of corpora lutea, the error rate
      was 24.1% and 17.2% for rectal palpation and ultrasonography respectively. The
      comparison of rectal palpation and macroscopy showed that three small corpora
      lutea and two corpora lutea with small cavity were determined wrongly as small
      follicles and two corpora lutea were determined whereas they were not present
      actually. With ultrasonography four small C.I. could not be detected and one C.I.
      with cavity was wrongly determined as follicle. It was noticed that follicles
      bigger than 10 mm (F2 = 10-15 mm, F3 = 16-20 mm) could be determined more
      accurately by means of ultrasonography than by rectal palpation (with
      ultrasonography: F2 = 90.48%, F3 = 100.0%; with rectal palpation, F2 = 61.9%, F3
      = 200.0%). The correlation of the findings of rectal palpation or ultrasonography
      and blood progesterone levels was 86.2% and 89.7% respectively. This accordance
      was 96.6% for progesterone levels and waterbath and macroscopic findings.

PMID- 10916938
TI  - Treatment of wobbler syndrome in dogs with electroacupuncture.
AB  - Based on favorable experiences with acupuncture for the treatment of hind limbs
      paralysis, lumbo-sacral alterations, and other spinal cord problems; a clinical
      trial, involving 40 dogs affected with wobbler syndrome was carried out. Patients
      were graded in three categories according to the severity of each case and then
      randomly divided in two groups. Both groups contained all three grades. Group 1
      (20 dogs) was treated using orthodox medical and surgical interventions, while
      Group 2 (20 dogs) were treated mainly with electroacupuncture, and in few cases
      with surgical intervention as well. The study was carried out in a three-year
      period. Acupuncture treatments were given every other day delivering 150 to 300
      mVolts at 125 Hz, equivalents to approximately 20 microAmps, in ten acupuncture
      points per treatment. Deep needle insertion was used. Overall per cent success in
      Group I was only 20%, while in group II the corresponding value was 85%. The
      number of acupuncture treatments required to achieve full recovery in Group II
      was dependent upon the severity of the case, as follows: Grade I: 18.5 +/- 2.5;
      Grade II: 25 +/- 5.4; and Grade III: 34 +/- 6.7 (r = 0.962). No adverse effects
      were observed with acupuncture. The use of this technique is proposed for large
      scale clinical trials.

PMID- 10916939
TI  - Sequence analysis of E2 glycoprotein genes of classical swine fever viruses:
      identification of a novel genogroup in Thailand.
AB  - Thirty classical swine fever viruses (CSFV) isolated in Thailand between 1988 and
      1996 were characterised by genetic sequence analysis of a part of their E2 coding
      regions, comparing the new data with that for representative reference viruses
      from other countries and continents. Thai isolates were divided into three
      distinct genogroups, indicating multiple origins for the outbreaks. Eighteen
      isolates from 1988-1995 form a new genogroup not previously described from any
      other geographical region. Eleven isolates from 1988-1995 are in the same
      genogroup as old US and European strains represented by reference strains Alfort
      187 and Brescia. The viruses of this group seem to have died out in Europe but
      still persist in Thailand. One recent isolate from 1996 represents another
      previously described genogroup being closely related to Italian viruses isolated
      in the same year.

PMID- 10916940
TI  - [Blood flow in marginal gingiva as measured with laser   Doppler flowmetry].
AB  - The clinical application of laser Doppler flowmetry (LDF) provides data on the
      blood flow of marginal gingiva (GBF) at different dental regions. The aim of the
      present investigation was to study the GBF at different teeth. Ten adult subjects
      with good oral hygiene were involved in this experiment. In a series of
      experiments GBF was recorded bilaterally positioned the flow probe on three sites
      1 mm above the marginal gingiva of the upper and lower central incisors. In
      another series of investigations the same technique was used for GBF
      registrations at six permanent teeth on the right side (11-16; according to FDI
      notation). The mean blood flow values obtained at 3 different places of marginal
      gingiva of the front teeth were nearly identical, therefore the data were pooled.
      The GBF values registered at the six upper right teeth also showed close
      similarity (p > 0.30). No differences were observed between the mean GBF values
      at the left and right central incisors (p > 0.80). There was a significant
      gingival blood flow value elevation at lower incisors as compared to that in the
      upper jaw (p < 0.05). Our results indicate that there is homogeneous marginal
      blood perfusion both in the maxillary and mandibula healthy gingiva. However,
      difference exists in blood supply between the upper and lower jaws in favor of
      mandibular marginal gingiva.

PMID- 10916941
TI  - [Surface treatment of dental implants with high-energy laser beam]  .
AB  - In the present study the biological value of the laser prepared titanium implants
      has been investigated. Screw-type implants with different surface modifications
      were placed into the femurs of rabbits. Removal torque measurements and
      histological examinations were prepared. The examinations were divided into two
      groups. In the first part of the examinations the laser surface treatment was
      compared to other type of surface modifications. In the examination groups the
      implants were prepared with the following surfaces: 1. machined, 2. sandblasted,
      3. low intensity laser surface, 4. high intensity laser surface, 5. titanium
      oxide coated surface. In the second part of the examinations laser treatment with
      different physical variables were observed. It has been concluded, that in both
      cases the high energy laser treated implants needed higher removal torque and in
      some cases an osteogenic activity was observed around them in the medullary space
      as well. The authors think the advantage of laser surface treatment lies in
      special micromorphology and the increased cleanliness of the surface.

PMID- 10916942
TI  - [Study of the relationship of the mandibular alveolar tuberculum to the occlusal
      plane at complete lower dentures].
AB  - The distance between occlusal plane and alveolar crest has an influence on the
      stability of the lower denture. From the relationship of the occlusal plane to
      the tuberculum alveolare mandibulae we can conclude on the distance between the
      occlusal surface of the denture's molars and the alveolar crest. The relationship
      of the occlusal plane to the tuberculum alveolare mandibulae was examined in 688
      patients with complete lower and upper dentures. Results have shown, that in
      30.25% the occlusal plane of the lower dentures was at higher level, than the
      highest point of the tuberculum alveolare mandibulae, in 41.3% it was at the
      level of the highest point of the tuberculum alveolare mandibulae and in 28.45%
      it crossed the tuberculum below its highest point. From our results the
      conclusion can be drawn, that in most of the cases no attention to the tuberculum
      line, has been paid the interalveolar distance and the occlusal plane of the
      natural teeth at the set-up of the molars, so this has a negative effect in 69.5%
      of the examined cases on the stability of the lower complete dentures.

PMID- 10916943
TI  - [Colorectal cancer in spouses of colorectal cancer patients].
AB  - Married couples share home environments and life style for years. In the case of
      colorectal cancer, an association with insulin resistance was reported. We
      determined the presence of the insulin-resistance syndrome (IRS, 1 or more of the
      following: body mass index of > 25 kg/m2, diabetes, or hyperlipidemia) in 84
      colorectal cancer patients, of whom 61 patients (73%) had IRS. The incidence of
      the distal colorectal cancer, which has been declining in the United States, was
      significantly higher in the IRS group than in the non-IRS group (75.4 vs 52.2%, p
      = 0.0400). Some mechanisms may promote the progression of mucosal lesions to
      invasive cancers in the distal colorectum. There were no significant differences
      with respect to the age (64.6 +/- 9.4 vs 64.3 +/- 11.3 yr, p = 0.8298), height
      (159 +/- 9 vs 157 +/- 8 cm, p = 0.1375), and body mass index (22.2 +/- 3.6 vs
      22.4 +/- 2.7 kg/m2, p = 0.6364) between the patients and their spouses. In 84
      couples in whom colorectal cancer develops at least in one may then not
      illustrate the nursery rhyme: "Jack Sprat could eat no fat, His wife could eat no
      lean...". The spouses had been married for an average of 38 years, and in 30
      spouses who had been followed in a colorectal cancer screening, 5 developed
      colorectal cancer. To diminish the incidence of colorectal cancer in Japan, we
      might advise screening colonoscopy to the spouses of colorectal cancer patients,
      or deja vu all over again?

PMID- 10916944
TI  - [Histological identification of brainstem neurons related to generation of
      rhythmical jaw movements in the rat].
AB  - Rhythmical jaw movements (RJM) were induced by stimulation of the oral cavity or
      the cerebral peduncle in the anesthetized rat. We found that the phase-dependent
      rhythmical (RJM-phasic) neuronal activities were necessary for the generation of
      RJM and iontophoretic application of glutamate activated a small number of these
      neurons rhythmically in phase with simultaneous RJM (Glu-RJM-phasic neurons)
      although it activated most RJM-phasic neurons tonically without RJM. N-(2
      aminoethyl) biotinamide hydrochloride was iontophoretically applied to visualize
      these neurons. An identified Glu-RJM-phasic neuron had the complicated outline of
      soma with eight or more short and long dendrites. The RJM-phasic neurons had the
      simple outlines of soma (fusiform, triangular or rhomboid) with several short
      dendrites. Differential activation by glutamate corresponded to differential
      morphological characteristics of the brainstem neurons related to RJM-generation.

PMID- 10916945
TI  - Coloanal anastomosis: what's left for abdominoperineal resection?

PMID- 10916947
TI  - [Treatment of rectal carcinoma: our experience].
AB  - Authors' experience with 53 patient operated on for adenocarcinoma of the rectum
      in Oncologic Surgery Department--University of Messina (Italy) was analysed. The
      development of mechanical devices has allowed surgeons to perform sphincter
      saving in patients with medium-lower tumors of the rectum. In this experience
      abdominoperineal amputation was performed in cases of distal rectal tumors, local
      transanal excision was performed in 6 cases. There were no statistically
      significant differences between low anterior resection and abdomino-perineal
      resection with respect to local (17% vs 16.6%) and distant (16% vs 16%)
      recurrence.

PMID- 10916946
TI  - [Scintigraphy with 99mTc-HMPAO-marked leukocytes and abdominal tumors: clinical
      interpretation of scintigraphy results].
AB  - The 99mTc-HMAPAO-labelled leucocyte scan is a widely employed diagnostic tool in
      the assessment of inflammatory and infective diseases. Nevertheless, leucocytes
      accumulation in neoplastic lesions has been reported. In the present study, aimed
      at the exploration of the abdomen and performed on 62 patients, positive
      scintigraphic findings were obtained in 66.6% (4/6) of the neoplasms and in 6.45%
      (4/62) of the studied cases. These scintigraphic results, even if they have to be
      considered as false positive cases, effectively reflect histopathologic changes
      present in the neoplastic tissue. On the basis of the obtained results,
      leucocytes accumulation in abdominal malignancies is probably due to the presence
      of necrosis and ulceration and to the resulting infection of the tumour.

PMID- 10916948
TI  - [Common bile duct injuries during videolaparocholecystectomy].
AB  - In the years an increase of last biliary injuries during laparoscopic
      cholecystectomy was observed. At present this occurrence rate is 0.1-3.4% of
      laparoscopic procedures. Probably this is to be related to less contraindications
      to cholecystectomy by laparoscopic procedures, with increase of more difficult
      operations. The intraoperative biliary injuries are due to anatomical anomalies
      of the local structures, mistakes of technique, flogosis of the cholecisto
      choledocal region. Factors preventing iatrogenic injuries are accurate and
      standardized operative technique, adoption of modern instruments, intraoperative
      cholangiography. The Authors have reviewed their experience based on 1236
      laparoscopic cholecysectomies performed in six years (1992-1998) in their own
      structure. Four lesions of the biliary tract (0.3%) have occurred: three Bismuth
      I-II and one Bismuth IV. They have always performed intraoperative
      cholangiography, without false negative, in contrast with present literature.
      They conclude underlining the need of the routine contrastrographic study of the
      biliary tract in all cholecysectomies as well as of an adequate training in
      radiological imagines interpretation.

PMID- 10916949
TI  - [Morgagni-Larrey diaphragmatic hernia: report of a case].
AB  - The Authors presents a Morgagni-Larrey's diaphragmatic hernia case, observed
      during subocclusive manifestation. They emphasize the utility to perform always
      the surgical intervention, also in the asintomatic cases.

PMID- 10916951
TI  - Successfully managed genital necrotizing fasciitis with multiple debilitating
      diseases. A case report.
AB  - Genital necrotizing fasciitis is a rapidly progressive bacterial infection of
      soft tissues with a reported average mortality of about 36%; associated
      debilitating diseases increase the mortality rate. The Authors report a case of
      successful management, due to an aggressive medical and surgical therapy, despite
      the presence of multiple debilitating diseases and an advanced necrosis.

PMID- 10916950
TI  - [Unusual case of kidney rupture].
AB  - The Authors report a case of renal rupture in a patient 36 years with acute
      abdominal pain and progressive anaemia. The history of the patient shows no past
      signs and symptoms of either renal pathology or traumatic event. Radiological
      examinations demonstrates dislocation of the kidney through presence of large
      retroperitoneal formation interpretable as haematoma. Progressing bloodless, they
      proceeded to embolization of renal artery and successive nephrectomy. Only
      histological examination of the removed kidney demonstrates the presence of a
      renal clear cells adenocarcinoma.

PMID- 10916952
TI  - [Mesothelial cyst of the diaphragm. Report of a case and review of the
      literature].
AB  - A case of mesothelial cyst of the right hemidiaphragm in a 44 year old man is
      reported. Origin (most likely due to a recess of the primary coelomiatic cavity),
      topographical, histological and therapeutic features are discussed, stressing
      that it is now more frequently recognised thanks to progress in diagnostic
      imaging techniques. Complete surgical excision is mandatory to definitely
      differentiate such lesion from primary diaphragmatic neoplasm, not infrequently
      malignant.

PMID- 10916953
TI  - [Ultrasonography of acute colonic diverticulitis. Effect on surgical treatment].
AB  - The clinical diagnosis of acute colonic diverticulitis (ACD) is at times
      difficult and an early detection by a non-invasive method as ultrasonography (US)
      is required. The aim of this study is to evaluate the diagnostic sensibility of
      US performed on admission in patients with ACD, its value in monitoring
      assessment of severity and its influence on surgical decision. The Authors have
      carried out a retrospective study on 22 patients (8 men and 14 women, median age
      58 years) admitted from January 1997 to June 1999 for ACD. In 21 cases the
      diagnosis was made on admission by US. The diagnostic sensibility was 95.5%
      (false-negative: 1 case). The true diagnosis in 2 false-positive patients was:
      ischemic colitis (1 case), aspecific thickening of colonic wall in patient with
      left renal carcinoma (1 case). The sensibility of clinical evaluation on
      admission was 68% (false-negative: 7 cases). The clinical diagnosis was
      unequivocal in only 36.4% of cases. In 14 patients, successfully treated
      conservatively, the US gave monitoring the reduction of hypoechogenic thickening
      of the colonic wall. Seven patients who underwent urgent surgery: in 3 cases for
      generalized peritonitis, but in 4 patients (18.2%) the immediate management was
      influenced by US detection of a clinical misdiagnosed abscess. The Authors
      conclude that, in the hands of an expert investigator, the extensive use of US in
      acute abdominal pain facilitate an accurate diagnosis of ACD and its appropriate
      management.

PMID- 10916954
TI  - [Thyroid surgery in assisted local anesthesia].
AB  - To evaluate the advantages of thyroidectomy under assisted local anesthesia, 35
      cases operated on from January 1998 to February 1999 were reviewed. The patients
      were studied in ambulatory setting and adequately informed on the program of
      thyroid operation under local anesthesia. Multinodular goitre was present in all
      the cases. In 12 cases, it was intrathoracic. The morning of operation, all the
      patients underwent to pre-operative sedation and, in operative room, to local
      anesthesia with Mepivacaine 1% and adrenaline 1,200,000 U. The operations were
      performed with a mean of 30 cc of local anesthetic. During operation, in none
      case the conversion to general anesthesia was necessary. No mortality and
      morbility were registered. In the majority of cases, an analgesic was necessary
      meanly 4 hours after operation. The evening of operation in all the patient oral
      nutrition was restored. Twenty-nine patients were discharged from the hospital 48
      hours after surgery. Eight days after operation, surgical recovery was evident in
      all the patients reviewed in the out patients setting. The advantages of thyroid
      surgery under assisted local anesthesia are outlined.

PMID- 10916955
TI  - [Current role of open window thoracostomy].
AB  - The Open Window Thoracostomy (OWT) surgical method find its origin in the
      treatment of chronic tuberculous empyemas, in the cases where the drainage alone
      not permitted a sufficient cleaning of pleural cavity. In the recent years the
      indications for the execution of this method are extended also to metapneumoniae
      and post-pneumonectomy empyemas (for benign and malignant pathology), with or
      without bronco-pleural fistula, when these pathologies produces a general severe
      decline in the patient (septic shock). This method permit to effect a daily
      cleaning of a pleural cavity, through the introduction of a sterile gauzes imbued
      of specific antibiotic, reducing at least the purulent infection effects's
      previously present and favouring the reduction of the same cavity, in prevision
      of other reconstructive operations (thoracoplasty). Generally not many beloved by
      surgeons and patients (for the difficult management, aesthetic outcomes, the long
      stay in hospital), the OWT can often reestablish a dangerous situation,
      especially in the patients with a risk of septic shock. This study aims to
      analyse present indications, problems and therapeutics outcomes of this method,
      through the evaluation of 27 cases of OWT treated in the Department of Thoracic
      Surgery University of L'Aquila between the 1984 and the 1998.

PMID- 10916956
TI  - [Monitoring of postmenopausal women treated with tamoxifen for breast carcinoma].
AB  - The aim of this study was to evaluate the usefulness of different diagnostic
      tools in the screening for endometrial neoplasms in women receiving tamoxifen as
      adjuvant treatment after surgery for breast cancer. The Authors' experience,
      while confirming the importance of a very strict and careful follow-up, stresses
      the higher sensitivity and specificity of diagnostic hysteroscopy.

PMID- 10916957
TI  - Early experience with 'new federalism' in health insurance regulation.
AB  - The authors monitored the implementation of the Health Insurance Portability and
      Accountability Act (HIPAA) from 1997 to 1999. Regulators in all states and
      relevant federal agencies were interviewed and applicable laws and regulations
      studied. The authors found that HIPAA changed legal protections for consumers'
      health coverage in several ways. They examine how the process of regulating such
      coverage was affected at the state and federal levels and under an emerging
      partnership of the two. Despite some early implementation challenges, HIPAA's
      successes have been significant, although limited by the law's incremental
      nature.

PMID- 10916958
TI  - Uneasy alliances: managed care plans formed by safety-net providers.
AB  - Health care providers that have traditionally served the poor are forming their
      own managed care plans, often in alliance with local safety-net peers. These
      alliances make it easier to raise needed capital, increase the pool of likely
      enrollees, and enable plans to benefit from efficiencies of scale. At the same
      time, however, the alliances often are undermined by conflicts of interest among
      the different sponsors and between the sponsors and the plan. This paper suggests
      that these plans are most likely to do well when the state makes special efforts
      to help and when plans have the leadership and financial reserves to take
      advantage of their supportive state policies.

PMID- 10916959
TI  - Managing Medicaid managed care: are states becoming prudent purchasers?
AB  - This paper examines the extent to which five states are becoming "prudent
      purchasers" in their oversight of Medicaid managed care. Our conclusions are
      mixed. These states are making more sustained efforts along these lines than most
      private purchasers are and have improved the amount and quality of the data they
      collect on the experiences of Medicaid clients when compared with the traditional
      fee-for-service program. They have been less successful in ensuring data quality
      that is adequate to support contracting decisions and in developing the
      analytical or political capacity to use data to "manage" the managed care system.
      Becoming a prudent purchaser appears to be a complex task for states that may
      prove difficult to achieve.

PMID- 10916960
TI  - Health care use among undocumented Latino immigrants.
AB  - Using data from a 1996/1997 survey of undocumented Latino immigrants in four
      sites, we examine reasons for coming to the United States, use of health care
      services, and participation in government programs. We find that undocumented
      Latinos come to this country primarily for jobs. Their ambulatory health care use
      is low compared with that of all Latinos and all persons nationally, and their
      rates of hospitalization are comparable except for hospitalization for
      childbirth. Almost half of married undocumented Latinos have a child who is a
      U.S. citizen. Excluding undocumented immigrants from receiving government-funded
      health care services is unlikely to reduce the level of immigration and likely to
      affect the well-being of children who are U.S. citizens living in immigrant
      households.

PMID- 10916961
TI  - Barriers to care among racial/ethnic groups under managed care.
AB  - We describe barriers to care reported by racial/ethnic groups and explore the
      extent to which barriers vary between persons enrolled in managed care and those
      in non-managed care plans, using data from the 1996 Medical Expenditure Panel
      Survey (MEPS). Most respondents expressed satisfaction with their care; however,
      a substantial percentage reported experiencing barriers. Minorities, particularly
      Hispanics and Asian Americans, were more likely than non-Hispanic whites were to
      report barriers. Managed care enrollees across racial/ethnic groups faced
      different types of barriers than non-managed care enrollees did. Although managed
      care enrollees were more likely to report having a usual source of care and
      greater continuity of care, they also reported more difficulties obtaining care
      and less satisfaction with their care.

PMID- 10916962
TI  - Do patients choose physicians of their own race?
AB  - This study seeks to determine whether minority Americans tend to see physicians
      of their own race as a matter of choice or simply because minority physicians are
      more conveniently located within predominantly minority communities. Using data
      from the Commonwealth Fund 1994 National Comparative Survey of Minority Health
      Care, we found that black and Hispanic Americans sought care from physicians of
      their own race because of personal preference and language, not solely because of
      geographic accessibility. As minority populations continue to grow, the demand
      for minority physicians is likely to increase. Keeping up with this demand will
      require medical school admissions policies and physician workforce planning to
      include explicit strategies to increase the supply of underrepresented minority
      physicians.

PMID- 10916963
TI  - American health care and the law--we need to talk!
AB  - The first section of this paper highlights five critical legal developments over
      the past half-century that, while not reflecting considered policy judgments
      about how the health care industry should operate, put American health care on
      some surprising paths. The second part then observes five fundamental policy
      contradictions discernible in health care law today, each of which reflects
      severe ambivalence in public attitudes toward health care. Although such
      confusion in the law is interesting in itself, the main purpose of the paper is
      to propose, in section three, the creation of a permanent high-level forum,
      perhaps in the Institute of Medicine, where leaders from the health and legal
      worlds could meet regularly with a view to helping the legal system resolve some
      of the policy confusion that exists.

PMID- 10916964
TI  - Spending on mental health and substance abuse treatment, 1987-1997.
AB  - This paper is the result of an ongoing effort to track spending on mental health
      and substance abuse (MH/SA) treatment nationwide. Spending for MH/SA treatment
      was $85.3 billion in 1997: $73.4 billion for mental illness and $11.9 billion for
      substance abuse. MH/SA spending growth averaged 6.8 percent a year between 1987
      and 1997, while national health expenditures grew by 8.2 percent.

PMID- 10916966
TI  - A senator's quest to beat cancer. Interview by Fitzhugh Mullan.

PMID- 10916965
TI  - Setting rates for Medicaid managed behavioral health care: lessons learned.
AB  - This paper reviews Tennessee's experience setting, monitoring, and updating
      capitation rates for Medicaid managed behavioral health care, and draws lessons
      from those experiences for other states. Our review of assumptions about four
      components of Tennessee's rate-setting process--data, benefit design, savings
      expectations, and processes for monitoring and updating rates--suggests that the
      initial rate established by Tennessee was inadequate, and its inadequacy resulted
      primarily from the way available information was used to set the rate, rather
      than from the method of rate setting selected. Tennessee's experiences illustrate
      how difficult rate setting is and illuminate several key lessons about the rate
      setting process.

PMID- 10916967
TI  - On the 'efficiency' of managed care plans.

PMID- 10916968
TI  - Disclosing doctors' incentives: will consumers understand and value the
      information?
AB  - As part of a broader movement toward accountability in health care, federal and
      state governments have required health plans to disclose physicians' financial
      incentives. Available data suggest that patients have poor comprehension of the
      incentives and significant barriers to learning, including high trust in their
      physicians, reluctance to think of the physician/patient relationship in
      financial terms, and failure to understand the relevance of the information to
      their health care choices and treatment. Disclosure that conveys clearly what is
      at stake will increase the salience of incentive information but is also more
      likely to erode trust.

PMID- 10916969
TI  - Disclosure of physician incentives: do practices satisfy purposes?
AB  - Under legal pressure, discussion has quickly shifted from whether health plans
      should disclose how they pay their physicians to how, when, and what should be
      disclosed and by whom. This paper describes health plans' disclosure practices
      and evaluates their adequacy and likely impact. It begins by explaining how
      different reasons for disclosure alter the form and content of disclosure,
      illustrating these approaches with actual examples. The paper concludes with a
      recommended approach that attempts to layer and stage disclosures so that people
      have as much information as they want, when they need it.

PMID- 10916970
TI  - Increasing use of new prescription drugs: a case study.

PMID- 10916971
TI  - The nonpoor uninsured in California, 1998.

PMID- 10916972
TI  - Adults without health insurance: do state policies matter?

PMID- 10916973
TI  - Why does the number of uninsured Americans continue to grow?

PMID- 10916975
TI  - Selective chaos.

PMID- 10916974
TI  - Self-care among the uninsured: 'you do what you can do'.

PMID- 10916976
TI  - What's not to like about HMOs.

PMID- 10916977
TI  - Health care in the upcoming 2000 election.
AB  - Health care will be one of the top issues in the year 2000 election, but voters'
      interest in health care is not as great as it was in 1992. There is no single
      unifying theme to the health care issue. Rather, there are multiple concerns:
      making Medicare financially sound, providing coverage for prescription medicines
      for seniors, covering the uninsured, and addressing patients' rights. Voters
      favor an incremental approach to expanding health insurance coverage rather than
      a major program. They express about equal levels of support for plans similar in
      concept to those proposed by presidential candidates Al Gore and George W. Bush.

PMID- 10916978
TI  - Trends in Medicaid physician fees, 1993-1998.
AB  - This study uses data on Medicaid physician fees in 1993 and 1998 to document
      variation in fees across the country, describe changes in these fees, and
      contrast how they changed relative to those in Medicare. The results show that
      1998 Medicaid fees varied widely. Medicaid fees grew 4.6 percent between 1993 and
      1998, lagging behind the general rate of inflation. This growth was greater for
      primary care services than for other services studied. Relative to Medicare
      physician fees, Medicaid fees fell by 14.3 percent between 1993 and 1998.
      Medicaid's low fees and slow growth rates suggest that potential access problems
      among Medicaid enrollees remain a policy issue that should be monitored.

PMID- 10916979
TI  - Effects of case management and new drugs on Medicaid AIDS spending.
AB  - This study evaluates the effects of Florida's participation in the Medicaid
      acquired immunodeficiency syndrome (AIDS) home and community-based waiver and the
      use of recently developed AIDS drugs on spending per Medicaid beneficiary. We
      find that monthly Medicaid spending for waiver non-participants was significantly
      higher than was spending for waiver nonparticipants. The major reason for the
      cost difference is that nonwaiver enrollees incurred significantly higher
      inpatient costs than did those enrolled in the waiver. Although waiver enrollees
      had higher drug spending, these represent only a fraction of the higher inpatient
      costs incurred by nonwaiver enrollees. Thus, it appears that adherence to
      appropriate medications reduces the need for inpatient care. The case management
      approach of the AIDS waiver may have similar effects for persons with other
      chronic diseases.

PMID- 10916980
TI  - Health care use and at-work productivity among employees with mental disorders.
AB  - This study examines the differential medical care use and work productivity of
      employees with and without anxiety and with other mental disorders at a large
      national firm. A unique aspect of this study is that we integrate medical claims
      and employer-provided, objective productivity data for the same employees. We
      find extensive mental health comorbidities among anxious employees. Although
      medical care use differs considerably among employees having no, one, or several
      treated mental disorders, in most cases their annual average absenteeism and
      average at-work productivity performance do not differ. Differences among
      subgroups are observed for job tenure and maternity claims. We discuss these long
      term average productivity findings in relation to other literature encompassing
      shorter time periods.

PMID- 10916981
TI  - The HSRProj database: update on Health Services Research in Progress.

PMID- 10916983
TI  - Improving health care by looking outside the industry.

PMID- 10916982
TI  - Poor little rich men.

PMID- 10916984
TI  - Teaching hospital mergers: a cautionary tale.

PMID- 10916985
TI  - Getting the pharmacist involved.

PMID- 10916987
TI  - Expensive drugs: let doctors and patients decide.

PMID- 10916986
TI  - Clinical research is personal.

PMID- 10916988
TI  - Where should we be on the list?

PMID- 10916989
TI  - S.A.V.E. is a team effort when solving the violence puzzle.

PMID- 10916990
TI  - Hospital liable for breach of fiduciary duty by wrongfully releasing medical
      records.

PMID- 10916991
TI  - What every physician should know about HCFA's new Payment Error Prevention
      Program.

PMID- 10916992
TI  - Health plans should not have access to your financial records.

PMID- 10916993
TI  - Domestic violence.
AB  - Domestic violence is alarmingly prevalent, yet medical students, residents, and
      experienced physicians are often handicapped by insufficient knowledge and
      expertise in the diagnosis and care of these patients. This article reviews the
      epidemiology of domestic violence, highlights risk factors, discusses current
      obstacles in the diagnosis and treatment of domestic violence, identifies history
      taking and physical examination skills to increase diagnosis of this condition,
      and outlines treatment plans for victims.

PMID- 10916994
TI  - Declines in teenage birth rates, 1991-98: update of national and state trends.
AB  - OBJECTIVES: This report presents national birth rates for teenagers for 1991-98;
      the percent change, 1991-98; State-specific teenage birth rates for 1991 and
      1997; and the percent change, 1991-97. METHODS: Tabular and graphical
      descriptions of the trends in teenage birth rates by age group, race, and
      Hispanic origin of the mother are discussed. RESULTS: Birth rates for teenagers
      15-19 years declined nationally between 1991 and 1998 for all age, race, and
      Hispanic origin populations, with the steepest declines recorded for black women.
      State-specific rates by age fell in all States, with most declines statistically
      significant; overall declines ranged from 9 to 32 percent.

PMID- 10916995
TI  - Births, marriages, divorces, and deaths: provisional data for August 1999.

PMID- 10916996
TI  - [Adsorption in the treatment of uremia].

PMID- 10916997
TI  - [Peritoneal dialysis before renal transplantation. Elective procedure or risk
      factor?].

PMID- 10916999
TI  - [The white book of Spanish nephrology. (II). Spanish Society of Nephrology].

PMID- 10916998
TI  - [Genomics, pharmacogenomics, and medicine in the 21st century].

PMID- 10917000
TI  - [Renal osteodystrophy in Spain. Multicenter survey. (I). Collaborative Centers of
      the Multicenter Study on Renal Osteodystrophy].
AB  - In order to know the current management of renal osteodystrophy in Spain we
      collected data from 172 centres (10,724 patients) obtained from a 30 questions
      enquiry designed to show different aspects of the current management of renal
      osteodystrophy. The levels considered the "goal" for treatment were: Calcium 10
      10.5 mg/dL (53% of centres), 9.5-10 mg/dL (28%), 10.5-11 mg/dL (14%) and 9-9.5
      mg/dL (5% of centres). Phosphorus: between 4.5 and 5.5 mg/dL (77% of centres),
      between 5.5 and 6.5 mg/dL (15%) and less than 4.5 mg/dL (8% of centres).
      Parathormone (PTH): between 120 and 250 pg/mL (75% of centres), between 60 and
      120 pg/mL (19% of centres). The calcium concentration used in the dialysis fluids
      was 2.5 in 44% of centres, 3 in 28%, 3.5 in 26% and 2 mEq/L in the remaining 2%
      of centres. Pulse therapy was started with PTH higher than 750 in 16% of centres;
      with PTH higher than 500 pg/mL in 52% and with PTH higher than 250 pg/mL in 28%
      of the centres. Only 51% of centres decreased the calcium concentration in
      dialysis fluids when the patients were receiving parenteral calcitriol. Fifty
      nine percent of centres considered a positive response to treatment any reduction
      in PTH levels, 24% of centres considered response a decrease of at least 20%, 78%
      of centres maintained the treatment with calcitriol 6 months before deciding if
      the patient was a "responder" or a "non-responder". Parathyroidectomy was
      performed when PTH was higher than 1,000 pg/mL in 38% of the centres; in 41% when
      PTH was between 1,000 and 750; in 19% when PTH was between 750 and 500; and when
      PTH was between 500 and 250 pg/mL in the remaining 2% of the centres. Five
      percent of the patients had a parathyroidectomy.

PMID- 10917001
TI  - [Bone metabolic markers and use of vitamin D in dialysis. Multicenter survey.
      (II). Collaborative Centers of the Multicenter Study on Renal Osteodystrophy].
AB  - Renal osteodystrophy has become one of the most important aspects related with
      morbidity in dialysis patients. The aim of our study was to analyse the main
      biochemical markers of mineral metabolism in 7,422 dialysis patients from 147
      Spanish centres. We present data about serum Ca, P, Ca-P, product, Al and vitamin
      D. Due to the distribution of the analytical results (not normal), non-parametric
      tests were used. In this analysis a p < 0.01 was considered as significant. The
      mean total levels were: Ca 9.7 +/- 0.9 mg/dL; P 5.6 +/- 1.6 mg/dL; Ca-P product
      54 +/- 16 mg/dL; PTH 294 +/- 360 pg/mL and Al 27 +/- 23 micrograms/L. There was a
      great variation particularly on serum Ca and PTH levels. On the contrary, serum P
      and Ca-P product values were less spread: only a quarter of the patients had P
      levels higher then 6.5 mg/dL and one third Ca-P product higher than 60. Fifty
      percent of patients had Al levels lower than 20 micrograms/L. Forty one percent
      of patients (2,811 out of the 7,422) had a PTH equal or lower than 120 pg/mL and
      23% have PTH equal or lower than 60 pg/mL. Patients with PTH equal or lower than
      60 have serum Ca levels significantly higher than the remaining patients, on the
      contrary, serum P, Ca-P product and Al levels were significantly lower. In this
      group, 21% of patients were receiving vitamin D (in spite of low PTH). On the
      contrary 32% of patients were not receiving calcitriol (despite PTH higher than
      250 pg/mL). Forty four percent of patients were receiving vitamin D (46% on
      haemodialysis and 31% on peritoneal dialysis). Patients on haemodialysis showed
      serum Ca, P, PTH and Al levels higher than patients on peritoneal dialysis.

PMID- 10917002
TI  - [Hemodialysis with 2.5 mEq/L of calcium in relative hypoparathyroidism: long-term
      effects on bone mass].
AB  - Low PTH secretion is known to be associated with Adynamic Bone Disease (ABD).
      Positive balance calcium by CaCO3 or dialysate calcium (DCa) might play a role in
      the parathyroid gland suppression and a decrease in DCa to 2.5 mEq-l or lower has
      been proposed. The long-term effect of this procedure on bone mineral density
      (BMD) has not been established. The aim was to evaluate the effect of lowering
      dialysate calcium on bone mass in patients with relative hypoparathyroidism. We
      studied 20 patients with intact PTH below 120 pg/ml, using 3 mEq/l DCa and CaCO3
      as sole phosphate binder. Sex: 10M/10F. Age: 57 +/- 13 yrs. Months on dialysis:
      40 +/- 29. None of them had previous renal transplantation, parathyroidectomy nor
      aluminic toxicity. BMD of the lumbar spine was assessed by Quantitative Computed
      Tomography (QCT). They were randomized in two groups (GI and GII), with similar
      age, sex, and time on dialysis. There were no difference in BMD, levels of intact
      PTH, serum calcium, phosphate and AP (Alkaline Phosphatase) GI (n = 11; 5M/6F)
      was transferred to 2.5 mEq/l DCa and GII (n = 9; 5M/4F) continued using 3 mEq/l.
      BMD was measured one year later. Calcium, phosphate and AP were measured monthly
      and PTH every three months. After one year of hemodialysis with 2.5 mEq/l of
      calcium dialysate, BMD showed a significant reduction. BMD mg/cc Baseline (B):
      146.09 +/- 54; Final (F): 125.42 +/- 54 (p < 0.01). Z-score B: 0.13 +/- 1.89; F: 
      0.68 +/- 1.89 (p < 0.05). GII did no show change. The mean change: GI: -15 +/-
      13%, GII: 1.28 +/- 17% (p < 0.05); Z-Score GI: -0.81 +/- 0.92, GII: 0.27 +/- 0.67
      (p < 0.01). A separate analysis of BMD in both sexes (GI) revealed a tendency for
      females to lose more bone mineral than males: F: = 17.12 +/- 7.1%. M: -12.23 +/-
      18.6% (ns). GI: PTH and AP increased: PTH B: 38.75 +/- 41; F: 99 +/- 69 (p <
      0.01); AP: B: 118.4 +/- 47; F: 152 +/- 38 (p < 0.01). GII: PTH B: 53.8 +/- 28; F:
      79 +/- 5 (ns). AP: B: 125.1 +/- 36; F: 138 +/- 38 (ns). The rate of BMD loss
      inversely correlated with the increase of PTH (r = -0.61, p < 0.01). Serum
      calcium and phosphate did not change. In GI CaCO3 doses were: B: 332 +/- 261; F:
      537 +/- 260 (as grams of element calcium, every three months, p < 0.01). By
      multiple lineal regression only delta PTH and DCa were predictors of greater BMD
      loss. In conclusion, the use of 2.5 mEq/l dialysate calcium resulted in: 1) Loss
      of trabecular vertebral bone mass. 2) Increase in PTH secretion and biochemical
      markers of bone formation. 3) A greater CaCO3 dose.

PMID- 10917003
TI  - [L-arginine-nitric oxide pathway in hemodialysis].
AB  - Nitric oxide (NO) is derived from the metabolism of the amino acid L-arginine by
      NO synthase (NOS). One of the forms of NOS (i-NOS) can be induced by cytokines,
      bradykinin and endotoxin. During hemodialysis (HD), blood-dialysis membrane
      interaction can induce production of these mediators. HD can also induce changes
      of asymmetrical dimethylarginine (ADA), a potent inhibitor of NOS. The aim of
      this study was to investigate the effect of HD, using cuprophane (C,
      polyacrilonytrile (PAN) and special polyacrylonitrile (SPAN) membranes, on
      cellular NOS activity, and changes of plasma tumor necrosis factor (TNF-alpha),
      bradykinin, ADA and nitrate concentration. Before HD, cellular i-NOS activity was
      similar with the three membranes. Cuprophane HD induced a significant increase in
      i-NOS activity from 31 +/- 10 to 48 +/- 12 fmol-1 10(6) cells (p < 0.05). No
      changes were found in PAN and SPAN HD. The TNF-alpha values increased
      significantly during HD with C (56 +/- 6 vs 47 +/- 5 pg/ml, p < 0.05). No changes
      of bradykinin concentration were found during HD. A significant decrease of ADA
      and nitrate levels was observed during HD with three membranes. No significant
      correlation was found between percentage increase in i-NOS activity and the
      changes in other parameters. These findings suggest that HD with bioincompatible
      membranes can induce activation of cellular i-NOS.

PMID- 10917004
TI  - [Comparison of dialyzers in on-line hemodiafiltration].
AB  - At present we have a great variety of high-flux dialyzers whose characteristics
      in vitro seem similar. On-line HDF is a technique which combines diffusion with
      elevated convection and uses dialysate as replacement fluid. On-line HDF provides
      the highest clearances for small, medium-sized and large molecules and gives the
      best performance from the dialyzers. Conscious of this wide choice of dialyzers
      we evaluated the performance of different dialyzers in renowing small and medium
      large molecules. Eleven patients were included in this study, 7 males and 4
      females. Every patient received 11 on-line HDF sessions with Fresenius 4008B
      machine, Qi 100 ml/min or 6 L/h, QB 400 ml/min, QB 800 ml/min, UF 0.5 L/h and Td
      60 min. Only the dialyzer was changed: 1.9 m2 cellulose triacetate (Tricea 190G),
      2.1 m2 poly methyl methacrylate of PMMA (BK-2.1P), 1.8 m2 polyester-polymer Allol
      or PEPA (FLX-18GWS), 2.05 m2 acrylonitrile (Filtral 20), 2.1 m2 polyamide
      (Poliflux 2.1) and 1.8-2.4 m2 polysulfones (HF 80, BS-1.8S, APS-900, Arylane H9,
      Idemsa 2000, HdF 100). Arterial pressure, venous pressure and transmembrane
      pressure (TMP) were monitored. Plasma, urea, creatinine, phosphate, uric acid and
      beta 2m concentrations were measured at the beginning and at the end dialysis
      from arterial and venous blood lines, and arterial blood line with the slow flow
      method. Recirculation, dialyzer solutes clearance and solute reduction rates were
      calculated. No significant differences were found in arterial pressure, venous
      pressure and recirculation. Small molecule removal was similar except in BK-2.1P
      and HdF 100 dialyzers which were lower and higher respectively. There were
      differences in TMP and beta 2m removal among dialyzers employed. Mean TMP, beta
      2m clearance and beta 2m reduction ratio were: Tricea 190G (TMP 336 mmHg, beta 2m
      K 79 ml/min and beta 2m reduction ratio 44.9%), BK-2.1P (TMP 485, beta 2m K 102
      and beta 2mRR 48.3%), FLX-18 GWS (TMP 195, beta 2m K 140 and beta 2mRR 54.6%),
      Filtral 20 (TMP 245, beta 2m K 132 and beta 2mRR 54.1%), Poliflux 2.1 (TMP 209,
      beta 2m K 158 and beta 2mRR 56.0%), HF 80 (TMP 208, beta 2m K 160 and beta 2mRR
      57.4%), BS-1.8S (TMP 186, beta 2m K 179 and beta 2mRR 59.6%), APS-900 (TMP 174,
      beta 2m K 176 and beta 2mRR 64.8%), Arylane H9 (TMP 206, beta 2m K 171 and beta
      2mRR 59.9%), Idemsa 2000 (TMP 203, beta 2m K 169 and beta 2mRR 60.4%), HdF 100
      (TMP 152, beta 2m K 186 and beta 2mRR 64.6%). CONCLUSIONS: Of the dialyzers
      evaluated in on-line HDF, cellulose triacetate and PMMA have a smaller beta 2m
      removal and their use is limited by an elevated TMP. The polysulfones provide
      greater beta 2m removal with lower TMP, particularly the APS-900 and HdF 100
      dialyzers. The acrylonitrile, PEPA and polyamide are intermediate.

PMID- 10917005
TI  - [Methods to assess the ex vivo growth capacity of mesothelial cells obtained
      directly from peritoneal effluent].
AB  - The anatomical and functional integrity of mesothelial cells (MC) is necessary
      for peritoneal membrane stability. At present, there is no satisfactory method to
      assess MC function and regenerative capacity in individual peritoneal dialysis
      (PD) patients. MC may be cultured from peritoneal biopsy specimens, but
      peritoneal biopsy is an invasive procedure that cannot be performed serially. The
      aim of this study is to explore the feasibility of serial culture of MC from the
      peritoneal effluent of PD patients. Fifty-two randomly selected PD patients were
      studied. MC were obtained from the peritoneal effluent of nocturnal 2.27% glucose
      exchanges and cultured in T25 tissue culture flasks. Subconfluent MC cultures
      were obtained in 80.7% of patients. At this stage, the percentage of cells in the
      tissue cultured flask characterized as MC by morphology and immunostaining had
      increased to 95.5%. MC were then subcultured in multi-well culture plates, where
      they showed exponential cell growth until day 16. Nine (17%) patients released
      low numbers of MC into the effluent and MC could not be cultured to
      subconfluence. One additional patient released and apparently adequate number of
      MC that repeatedly failed to reach confluence. Patients showed the same behavior
      in several cultures performed. In conclusion, peritoneal MC released into
      peritoneal effluent are accessible for profound analysis by a culture technique.
      This technique opens the possibility of serial follow-up of the biology of MC
      individual PD patients.

PMID- 10917006
TI  - [Approximation to cost analysis of various types of hemodialysis using relative
      value units].
AB  - Hemodialysis sessions performed in Hospital Units have a different degree of
      complexity depending on the kind of patients who is receiving this treatment.
      This paper's aim is to apply certain weighting factors, which measure the
      complexity of each type of session performed, and so allow a more realistic
      comparison with hemodialysis sessions performed in dialysis Units. The various
      costs of the Castellon General Hospital Dialysis Unit were calculated. Five types
      of Hospital-performed sessions were defined, to which were applied concrete
      weighting factors called Relative Value Units (RVU). These took account of health
      professionals' time, disposable material and drug expenses. The cost of single
      hemodialysis session, before the RVU calculation was added, was 28,549 pesetas
      (171.58 Eu.). Thirty-two per cent of the cost was from disposable material,
      29.38% for cost of health professionals time, 18.54% for structural costs, 13.4%
      for drug expenses, and 5.73% for the nephrologists' time. When RVU were applied,
      the Type I session cost (chronic renal failure patients on regular hemodialysis),
      was 28,882 pesetas (149.54 Eu.). As the complexity of the procedure increased, up
      to the Type V session (acute renal failure patients in intensive Care Units), the
      costs also rose to 68,448 pesetas (411.38 Eu.). We conclude that weighing the
      different types of hemodialysis sessions by means of RVU, allows a better
      measurement of the costs and achieves a more accurate comparison with others
      hemodialysis units.

PMID- 10917007
TI  - [Treatment of idiopathic membranous glomerulonephritis with steroids and
      immunosuppressors].

PMID- 10917008
TI  - [Strategies for the prevention of peritoneal catheter exit site infection].

PMID- 10917009
TI  - [Mycophenolate mofetil and cough in pediatric patients].

PMID- 10917010
TI  - Herbert C. Conaway, Jr, MD.

PMID- 10917011
TI  - Physician practice support in transition.

PMID- 10917013
TI  - Update on physician education and training requirements.

PMID- 10917012
TI  - Research and practice: ethics at a muddled middle.

PMID- 10917014
TI  - Advanced practice nursing: a boon to physicians.

PMID- 10917015
TI  - HMO accountability in New Jersey.

PMID- 10917016
TI  - MSNJ Alliance: looking back on the past year.

PMID- 10917017
TI  - [Cytokine and cytokine receptor deficiencies causing defects in T cell/Th 1 cell
      differentiation and function].

PMID- 10917018
TI  - [A case of systemic lupus erythematosus associated with superior vena cava
      syndrome].
AB  - We report on a case of systemic lupus erythematosus associated with superior vena
      cava syndrome. A 46-year-old woman developed polyarthralgia in December 1994. She
      was treated with nonsteroidal anti-inflammatory drugs. In February 1995, she was
      admitted to our hospital with systemic convulsion and disturbance of
      consciousness (III-300/Japan coma scale). Severe facial edema was also present.
      Laboratory studies revealed the presence of anti-nuclear antibody, anti-DNA
      antibody, anti-Sm antibody, and proteinuria. An X-ray film of the chest showed
      pericardial effusion and bilateral pleural effusions. Computed tomography of the
      chest showed a severe swelling of mediastinal lymph nodes. A diagnosis of
      systemic lupus erythematosus was made according to the American Rheumatism
      Association criteria. Initial treatment with intravenous dexamethasone improved
      the level of consciousness and decreased the facial edema, mediastinal
      lymphadenopathy, and the effusions on computed tomography of the chest. We
      believe that the most likely explanation for the facial edema is superior vena
      cava syndrome due to severe mediastinal lymphadenopathy.

PMID- 10917019
TI  - [A case of aseptic osteomyelitis with heel ulcer improved by steroid
      application].
AB  - A 43-year-old male patient was admitted to our hospital because of left heel pain
      and fever. He had had swelling of the left ankle joint and pain 4 years prior to
      this, and 4 years later, he was admitted to another hospital when left heel ulcer
      and fever developed. The ulcer was diagnosed and treated as a diabetic ulcer
      because of hyperglycemia. In spite of good control of blood sugar, the ulcer
      became enlarged and the pain deteriorated, so he was transferred to orthopedics.
      Antibiotics produced no response, and culture from a specimen of the ulcer was
      negative. However, severe inflammatory response was seen in blood examination.
      MRI and scintigram of his left foot showed disseminated low intensity areas and
      accumulation in the tarsal bone area, so osteomyelitis was suspected. A biopsy of
      the ulcer showed infiltration of inflammatory cells into the dermis. We
      considered amputation of the left lower leg at first. However the biopsy result
      suggested an autoimmune mechanism, so prednisolone was administered. As a result,
      the ulcer and pain both diminished. This case was similar to pyoderma gangenosum,
      however this diagnosis cannot explain osteomyelitis or all its symptoms. We
      expect that there must be other case report with the same symptoms.

PMID- 10917020
TI  - [Visual disturbance of the elderly people].

PMID- 10917021
TI  - [Nuclear receptors-ligands, cofactors and target genes].

PMID- 10917022
TI  - [Effects of interventional therapy on the outcome of acute myocardial infarction
      in the elderly; a multicenter collaborative study in Japan and the study in Tokyo
      Metropolitan Geriatric Hospital].

PMID- 10917023
TI  - [Long-term prognosis after reperfusion therapy for acute myocardial infarction in
      elderly patients].
AB  - Although it has been well demonstrated that TIMI grade 3 flow is associated with
      improved survival after acute myocardial infarction in non-elderly patients, its
      implication in elderly patients has not been clarified. To assess this issue,
      1,115 patients with acute myocardial infarction who underwent coronary
      angiography within 24 hours after the onset of chest pain were studied: there
      were 131 elderly patients (age > or = 75 years) and 984 non-elderly patients (age
      < 75 years). Follow-up was achieved for 1,092 patients (98%). Elderly patients
      were associated with more female, Killip class > or = 2, 3 vessel disease and non
      smokers. Although modality of reperfusion therapy was not different, final TIMI
      flow grade was less frequently obtained in elderly patients (53% vs 65%, p =
      0.005). Elderly patients were associated with higher in-hospital mortality (25%
      vs 9%, p < 0.001) and lower 10 years cardiac death free rate (p < 0.001). Cox
      proportional hazards model showed that final TIMI flow grade 3 was an independent
      predictor of 10 years cardiac death free in elderly patients (odds ratio (OR) =
      0.39, 95% confidence interval (CI) = 0.20-0.74, p = 0.004) as well as non-elderly
      patients (OR = 0.41, 95% CI = 0.29-0.58, p < 0.001). In conclusion, our data
      suggest that final TIMI grade 3 flow is an important determinant to improve short
      and long-term survival after acute myocardial infarction in elderly patients as
      well as in non-elderly patients.

PMID- 10917024
TI  - [Early management of acute myocardial infarction in the elderly].
AB  - The efficacy of reperfusion treatment has been established in patients with acute
      myocardial infarction (AMI), however, its role is still controversial in the
      elderly patients. Data from Kochi Acute Myocardial Infarction Registry,
      consisting of 1,248 cases, showed that, compared to younger patients, elderly
      patients had greater ratio of women, painless infarction, delayed presentation,
      worse Killip classes, lower reperfusion procedure and higher mortality. To
      clarify the early management of AMI in the elderly, we analyzed the clinical data
      of 1,160 cases, according to age subgroup (317 advanced elderly, aged 75-84; 438
      elderly, aged 65-74; 405 middle-aged, aged 45-64) and according to the period
      (term I, 1990-92; term II, 1993-95; term III, 1996-98). RESULTS: 1) The advanced
      elderly received less reperfusion treatment (37% vs. 65%) and showed higher
      mortality (21% vs. 8%), compared to middle-aged patients. 2) In advanced elderly
      patients, mortality was reduced (term I, 27%; term II, 20%; term III, 19%),
      according to increasing application of reperfusion treatment (term I, 22%; term
      II, 45%; term III, 40%). 3) Inoadvanced elderly patients with reperfusion
      treatment, thrombolysis resulted in a higher mortality (17% vs. 7%) compared to
      direct angioplasty, probably due to increased incidence of cardiac rupture and
      pump failure in this age group. CONCLUSIONS: Reperfusion treatment improves
      mortality of AMI even in elderly patients. To minimize complications, direct
      angioplasty may be better for elderly patients.

PMID- 10917025
TI  - [Primary angioplasty for acute myocardial infarction in elderly patients].

PMID- 10917026
TI  - [Invasive procedures in frail older patients with coronary heart disease].

PMID- 10917027
TI  - [A six year follow-up study on the influence of silent ischemic brain lesions on
      cognitive function and brain atrophy in elderly people].
AB  - METHODS: To investigate the influence of silent ischemic brain lesions (silent
      brain infarction (SBI) and periventricular hyperintensity (PVH) on cognitive
      function and brain atrophy, we studied MRI and cognitive tests in 27 healthy
      elderly people (above 65 years old) for 6 years. We examined Okabe's Scale for
      verbal intelligence, Koh's Block Design Test for performance intelligence and
      Zung's Self-rating Depression Scale (SDS). On MRI, lesions with high intensity on
      T2-weighted image and low intensity on T1-weighted image, and which were larger
      than 3 mm were diagnosed as SBI. The PVH was classified into 5 grades (0-4), and
      we divided the subjects into the PVH 0-1 group and the PVH 2-4 group. We
      evaluated brain atrophy using the ventricular area index (VAI) (the ratio of
      ventricular area to intracranial area at the level of lateral ventricle) on MRI
      by NIH image 1.55 (Macintosh). RESULTS: The SBI group and the PVH 2-4 group
      showed significant decline in Okabe's Score, and Koh's IQ, increase in SDS and
      VAI during six years. On the other hand, the non-SBI and the PVH 0-1 group showed
      a decline only in Okabe's score, and an increase in VAI. The rate of change in
      VAI was significantly higher in the subjects with SBI than those without it.
      However, there was no significant difference in the VAI change rate between the
      PVH 2-4 group and the PVH 0-1 group. CONCLUSION: Silent ischemic brain lesions
      such as SBI and PVH may have significant influence on decline of cognitive
      functions and progression of brain atrophy even in healthy elderly people.

PMID- 10917028
TI  - [Copper supplement with cocoa for copper deficiency in patients with long-term
      enteral nutrition].
AB  - Copper deficiency (normal serum copper level: 78-136 micrograms/dl) has been
      reported in patients with long-term enteral nutrition, caused by a copper deficit
      in enteral nutrition. Occasionally, this leads to anemia and leukopenia. We used
      Hershey's pure cocoa that is rich in copper (content 3.8 mg/cocoa 100 g) for
      copper deficiency. A total of 86 (40 men and 46 women, mean age 69 years)
      patients on enteral nutrition were studied. The primary diseases were cerebral
      vascular disease in 71 patients, neurological disease in 5 and others in 10.
      Those who showed serum copper levels of 20 micrograms/dl or less (N = 8) were
      given 30-45 g of cocoa (copper content 1.14-1.71 mg) per day for about 40 days.
      Among them, two patients could not continue because of vomiting and diarrhea and
      were excluded from this study. Mean serum copper levels increased from 8.7 +/-
      6.2 to 99.0 +/- 25.4 micrograms/dl (N = 6). Those who showed serum copper levels
      20-77 mg/dl (N = 31) were given 10 g of cocoa (copper content 0.38 mg) per day
      for about 40 days. When mean serum copper levels increased from 50.5 +/- 19.3 to
      89.0 +/- 12.9 micrograms/dl with cocoa administration, anemia and neutropenia
      caused by copper deficiency showed a tendency to improve. After completing the
      study period, cocoa was reduced to 5 g (copper content 0.19 mg) per day in 23
      patients. The mean serum copper levels increased from 90.7 +/- 10.4 to 100.6 +/-
      17.1 micrograms/dl for about 100 days. Recently, the amount of daily copper
      requirement for adults has been reported to be 1.28-2.5 mg per day. We showed
      that 10 g of cocoa (0.6 mg total copper: 0.38 mg in cocoa and 0.22 mg in other
      nutrients) is sufficient to treat copper deficiency, and 5 g of cocoa (0.37 mg
      total copper: 0.19 mg in cocoa and 0.18 mg in other nutrients) is enough to
      maintain the normal level of serum copper in patients with long-term enteral
      nutrition.

PMID- 10917029
TI  - [Usefulness of nitrendipine and its effects on quality of life and brain blood
      flow in elderly hypertensive patients].
AB  - There are many reports on the efficacy of Ca-antagonists for treatment of elderly
      essential hypertension. In particular, many studies have noted the beneficial
      effects of antihypertensive therapy on the quality of life (QOL). Nevertheless,
      there are no reports on antihypertensive therapy regarding the relationship
      between brain blood flow (BBF) and QOL. Therefore, we examined the efficacy of
      nitrendipine, a Ca-antagonist, on the brain blood flow and QOL, and its side
      effects in elderly essential hypertensive patients. The subjects were 17 (males:
      4, females: 13) patients with untreated hypertension of WHO stage I or II, aged
      70 years or older. The mean dose of nitrendipine was 9.4 +/- 0.4 mg daily. Before
      and 6 months after treatment, we examined blood pressure (BP), heart rate (HR),
      echocardiography (left ventricular mass index [LVMI], % fractional shortening [%
      FS]), plasma noradrenaline (Nad), plasma renin activity (PRA), BBF using the IMP
      ARG method with BBF scintigraphy, and QOL was examined with a questionnaire. Two
      patients were excluded from this study because 1 had no decrease in BP, and
      another was moved to a different hospital. BP significantly decreased from 178/93
      to 137/77 mmHg, but HR was not changed after treatment. BBF significantly
      increased from 37.0 +/- 4.9 to 41.0 +/- 4.9 ml/dl/min, but % FS, Nad, and PRA did
      not significantly change. The degree of QOL was improved by 4.2 +/- 1.2 points
      and there was a significant positive correlation between the changes of BBF and
      of QOL (r = 0.66, p = 0.04). However, moderate pharmacotherapy for BP seems to be
      necessary because there were 2 patients whose BBF decreased accompanied by
      excessive drop in BP after treatment. In conclusion, it is possible to safely use
      nitrendipine for elderly essential hypertensive patients. Nitrendipine has
      beneficial effects on BBF, and it was suggested that the increase of BBF is one
      of the most important factors in improvement of QOL.

PMID- 10917030
TI  - [Repeated pulmonary aspiration in the aged demented patients].
AB  - We investigated the aged demented inpatients who had repeated aspiration in our
      hospital during a period of 21 months from July 1997. Subjects are 60 patients
      aged from 65 to 94. We investigated the clinical background of the subjects,
      dividing them into the group with pneumonia and the group without pneumonia, and
      compared their type of dementia, grade of dementia, underlying diseases,
      laboratory data, diet, and outcome. We further compared the effect of mucoid diet
      for pneumonia. The most common underlying diseases were hypertension,
      cerebrovascular disease, diseases of the digestive system, and malignant tumor.
      There was no statistically significant difference in the outcome of the two
      groups. Within the subjects, death due to pneumonia was statistically
      significantly less in patients who had a mucoid diet. These findings suggested
      that a mucoid diet is useful for the protection against death caused by
      aspiration pneumonia.

PMID- 10917031
TI  - [Relation between end point of activities of daily living and organ failure with
      bed rest].
AB  - To of improve the patient's quality of life while maintaining them in good
      conditions, it is important not to bring them to an irreversible conditions as a
      result of activities of daily living (ADL). To achieve this, establishment of the
      end point of ADL load is necessary. Questionnaires on judgment criteria for bed
      rest filled out by 218 doctors, who were cardiologists, neurologists, pulmonary
      specialists, gastroenterologists, nephralogists or hematologists, was surveyed.
      In the high risk disease patients I studied the worsening of the condition
      resulted in organ insufficiency, basd on which the appearance of end point was
      retrospectively established.

PMID- 10917032
TI  - [Progression of silent cerebral infarction in Japanese: a hospital-based study].
AB  - Little is known about the risk factors for progression of silent cerebral
      infarction (SCI). We evaluated the 5-year change in high signal intensity on T2
      weighted MR images of the brain in 50 asymptomatic patients with SCI. SCI
      progression was evaluated by the sum of the high intensity score (HIS) and the
      number of new lesions found on reexamination. Progression of SCI was seen in 19
      patients (38%) on the 5-year follow-up examination. The baseline HIS in the whole
      brain was 8.02 +/- 6.93 and the follow-up HIS was 8.7 +/- 7.16 (p < 0.001). SCI
      progression was frequently seen in the corona radiata (p < 0.02 or < 0.05) or
      posterior periventricular white matter (p < 0.05). Patients with poor control of
      hypertension (> 160/95 mmHg) have a higher prevalence of SCI progression (9/12
      (75%) vs. 10/38 (26.3%); OR = 8.4, p < 0.005) than the patients with effective
      control of BP (< or = 160/95 mmHg). The progression group showed a significantly
      higher baseline-HIS in the whole brain than the nonprogressing group (9.7 +/- 5.6
      vs. 7 +/- 7.5; p < 0.05). Neither age percentages of alcohol drinkers, male sex,
      current smokers, hypertensives, hyperuricemia, hypercholesterolemia, diabetes,
      obesity, left ventricular hypertrophy, ischemic heart disease, nor differences in
      the controls of diabetes and hypercholesterolemia during the study were different
      between the progressing and the nonprogressing groups. Our data showed that poor
      control of high blood pressure and the degree of T2 high intensity in the
      baseline were strong predictors of SCI progression.

PMID- 10917033
TI  - [Risk factors of anastomotic leak following operations for gastric cancer in the
      elderly].
AB  - The risk factors of anastomotic leak in the elderly following operations for
      gastric cancer were evaluated by multiple logistic model analysis. Data were
      taken from 705 operations over a 14-year period. The mean age of patients was
      75.8 +/- 7.6 years. The significant risk factors for anastomotic leak were
      amounts of intra-operative bleeding and male gender. No other factors were
      significant, including age, preoperative associated diseases, preoperative
      nutritional states and postoperative complications, some of which were, however,
      significant factors by univariate analyses. We conclude that we should make every
      endeavor to lower the amount of intra-operative bleeding in order to prevent
      postoperative anastomotic leaks in the elderly, especially in male patients.

PMID- 10917034
TI  - [A 75-year-old type 2 diabetes mellitus case responding strikingly troglitazone:
      possible mechanism of insulin resistance induced by insulin antibody].
AB  - A 75-years-old woman with poorly controlled type 2 diabetes mellitus, who was
      being treated by insulin therapy (Penfil N) was given troglitazon (400 mg/day)
      insulin combination therapy. Insulin therapy was stopped after several
      hypoglycemic attacks. Her blood sugar level improved within three months even
      recieving only troglitazone. Her high serum insulin level (453 microU/ml) was due
      to insulin antibody induced by insulin therapy. Cessation of troglitazone showed
      deterioration of glycemic control and gain of body weight. Examinations of
      insulin secretion and resistance indicated that the cessation of troglitazone
      induced insulin resistance. Resumption of troglitazone did not improve her blood
      glucose level again. Her serum insulin level had decreased due to discontinution
      of insulin therapy. Insulin resistance by insulin antibody might be one of the
      main reasons of her notable troglitazone reactivity. The relationship between
      troglitazone reactivity and insulin antibody should be elucidated in many cases
      in the future.

PMID- 10917035
TI  - Asa Gray in North Carolina. The beginnings of botany in the United States.

PMID- 10917036
TI  - A completely efficient life. Francis Henry Williams, MD, pioneer radiologist.

PMID- 10917037
TI  - A woman with anemia and a failing liver.

PMID- 10917038
TI  - Where we stand with treating dementia.
AB  - Our aging population is growing. As a result, dementia is becoming an ever more
      prevalent problem--with devastating consequences to the affected persons and
      their families. In the evaluation of the demented patient, it is crucial to look
      for and exclude conditions such as depression and other reversible causes of
      cognitive impairment before branding the patient with a diagnosis of dementia.
      Drug treatment of AD is not highly successful, although the Food and Drug
      Administration has approved acetylcholinesterase inhibitors for the treatment of
      mild to moderate AD. Present-day treatment for dementia focuses mainly on
      improving or preserving the quality of life of patients and their families, and
      on treating concomitant psychosocial, behavioral, and medical issues. We are
      optimistic that new, innovative medications may in the future allow us to treat
      or even cure Alzheimer's disease and other progressive dementing disorders.

PMID- 10917039
TI  - "There's no place like home". The Neonatal Home Management Program, Carolinas
      HealthCare System.

PMID- 10917041
TI  - 10 questions--and 10 answers--about the role of "statin" therapy after coronary
      artery bypass grafting.

PMID- 10917040
TI  - Periconceptional folic acid to prevent neural tube defects.

PMID- 10917042
TI  - Hypertension and associated risk factors in young African-American women
      attending a community health and wellness center.

PMID- 10917043
TI  - "Fixing" medical malpractice. One doctor's perspective of a non-system in need of
      national standardization.

PMID- 10917044
TI  - Interdisciplinary cooperative oncology for special head and neck malignancies.

PMID- 10917045
TI  - Transoral laser surgery for early glottic carcinoma.

PMID- 10917046
TI  - Tumors of the nasal cavity and the paranasal sinuses: an update of current
      opinions and advances in etiology, diagnostic and therapy.
AB  - Sinonasal malignant tumors account for a very small portion of the huge clinical
      spectrum in otolaryngology. There is an enormous histological diversity of tumors
      arising in the sinonasal system, demanding different therapeutic approaches.
      Sinonasal tumors, often diagnosed only in advanced stages, can be extremely
      disfiguring and the head neck surgeon has to deal besides cure and survival with
      quality of life aspects of his patient. It is impossible to cover all relevant
      aspects for the treatment of sinonasal neoplasias in a single presentation. This
      overview treats with epidemiology, etiology, molecular biological findings,
      diagnosis and new therapeutic concepts. Personal experiences will be presented
      along with advances in research and treatment of the last decade.

PMID- 10917047
TI  - Reconstructive surgery after tumorresection in the oral cavity and oropharynx.

PMID- 10917048
TI  - Growth regulation in head and neck carcinomas: the role of fibroblasts.

PMID- 10917049
TI  - Supracricoid laryngectomies: past, present, future.

PMID- 10917050
TI  - Glomus tumors.

PMID- 10917051
TI  - Application of navigation systems in skull base surgery.

PMID- 10917052
TI  - Supraglottic laryngectomy at the end of 20th century. Analysis of 200 cases with
      supraglottic surgery.

PMID- 10917053
TI  - Progress in basic research of otosclerosis.

PMID- 10917054
TI  - mRNA differential display of human laryngeal carcinoma cells and corresponding
      benign keratinocytes: cloning versus PCR-amplification.
AB  - The mRNA expression profile of mucosal keratinocyte cell lines was compared to
      that of squamous cell carcinoma cell lines of the head and neck (UMSCC-10A and
      UTSCC-19A) by the differential display technique. Before the sequencing
      procedure, the differentially expressed fragments can be reamplified either by
      PCR amplification only or by PCR amplification combined with molecular cloning.
      In this study, these two methods are compared. Total RNA of both cell types was
      reverse transcribed into cDNA followed by amplification with PCR. After
      electrophoresis in a non-denaturing gel, differentially expressed fragments were
      isolated, reamplified, and sequenced. Reamplification was carried out following
      two different protocols: the first one included two additional rounds of PCR, the
      second one only one additional round of PCR followed by cloning. Differentially
      expressed fragments could be sequenced after reamplification with both methods.
      Different cloned recombinants of the same PCR pool showed sequence differences in
      one to three bases. On the other hand, amplification of the differentially
      expressed fragment by PCR alone was reproducible without any differences in
      sequence. But in the latter case, only one of the complementary strands could be
      sequenced. Differentially expressed mRNA fragments detected by differential
      display can be sequenced directly after reamplification in two additional rounds
      of PCR. This method is no adequate replacement for bacterial cloning, but it
      might be a suitable solution if cloning procedures cannot be performed.

PMID- 10917055
TI  - Clinical implications of telomerase activity and inactivation of the tumor
      suppressor gene p16 (CDKN2A) in head and neck cancer.

PMID- 10917056
TI  - [Histological and clinical analysis of mesenchymal malignant neoplasms (soft
      tissue sarcomas) of head and neck region in the data of I ENT Department of
      Silesian Medical Academy].
AB  - Between the years 19890-1998 in I ENT Department of Silesian Medical Academy were
      treated surgically 15 patients suffering from soft tissue sarcomas of head and
      neck region. Patomorphological examination showed: fibrosarcoma (4 cases),
      haemangioendothelioma malignum (2 cases), rhabdomyosarcoma (2 cases), schwannoma
      malignum (2 cases), fibrohistiocytoma malignum (2 cases), tumor mixtus
      mesenchymalis (1 case), haemangiopericytoma malignum (1 case), extrasceletal
      osteosarcoma (1 case). Sarcomas were localised in paranasal sinuses (7 cases),
      orbita (5 cases), parapharyngeal space (1 case), parotid gland (1 case) and bucca
      (1 case). All those patients were treated surgically and most of them were
      irradiated postoperatively. The authors have presented the diagnostic and methods
      of treatment of soft tissue sarcomas. According to our experience and data of the
      literature the method of choice in treatment soft tissue sarcomas should consist
      of surgery and radiation therapy postoperatively.

PMID- 10917057
TI  - [Reconstructive surgery in larynx cancer].
AB  - Subtotal laryngectomies with larynx reconstruction are an acceptable alternative
      to the total laryngectomy in T2, T3 larynx cancer treatment. One procedure
      resection and reconstruction allow for radical oncological treatment with
      simultaneous preservation of air passage continuity and the function of the
      neolarynx. In the years 1988-1997 in ENT Dept. of Karol Marcinkowski University
      of Medical Sciences 38 subtotal laryngectomies with larynx reconstruction were
      performed. They were: 34 supracricoid laryngectomies with cricohyoidopexy, 2 with
      epiglotohyoidopexy and 3 supraglotic laryngectomies with reconstruction. The
      basic criterion of the evaluation of such procedures effectiveness was their
      oncological radicality. The follow-up period ranged from 2 to 9 years. Local
      relapse was observed in none of the cases, nodal relapse was started in 2
      patients. Another aspect taken into consideration was the function of the
      neolarynx. In 3 cases two or three laser procedures were performed because of
      neolarynx lumen structure which were followed by T-dren plasty. In 10 patients
      temporary swallowing difficulties, especially liquids, were observed in the first
      three month. Gastrostomy was performed in one case. The authors discuss
      indications to this type of surgery, operation technique, oncological and
      functional results. Spirometry results and voice analyses after larynx resection
      and reconstruction in these patients are presented.

PMID- 10917058
TI  - [Estimation larynx function after inhaled corticosteroids in the management of
      asthma].
AB  - The aim of study was the estimation larynx function in patients with chronic
      asthma after prolonged use of inhaled corticosteroids. Phoniatric examination and
      laryngovideostroboscopy were carried out. Patient were stayed under phoniatric et
      laryngologic control during the period of 12 months. Casual pharynx et larynx
      disorders were treated symptomatically. Dysphonia has been reported in the most
      of observed cases (70% patients). We explain it to be due to a laryngeal myopathy
      secondary to local corticosteroid effects. Larynx dysfunction was the reversible
      and did not depend of the corticosteroid use period.

PMID- 10917059
TI  - [Videorentgenocinematographic analysis of pharyngeal phase in the act of
      swallowing].
AB  - The course of the pharyngeal phase was analysed in physiological conditions. The
      mobility of anatomical structures taking part in the phase was evaluated, taking
      into consideration the time sequence in which the elements of the phase followed.
      To objectify the evaluation of the analysed phenomena, authors of this paper
      proposed and used linear and time parameters also used by other authors involved
      with these issues.

PMID- 10917060
TI  - [The results of treatment of middle ear carcinoma with radiotherapy].
AB  - We have described results of treatment patients with an extremely rare disease--a
      middle ear carcinoma. Through 25 years we have treated 37 patients. We recommend
      surgical treatment immediately supplemented by radiotherapy--because of
      anatomical difficulties in gaining enough histological margins. The median of
      survival time was 7 months in the group of palliatively treated patients and 14
      months in the group of radically treated patients. Three patients had following
      complications: a necrosis of retromandibular space and mandibular joint, a
      purulent otitis media and an osteoporosis of the temporal bone.

PMID- 10917061
TI  - [Myogenic vestibular evoked potentials used to objective estimation of
      effectiveness of central action drugs].
AB  - In this paper possibility of employing vestibular evoked myogenic potentials
      (VEMPs) was evaluated to following efficacy of drug effect in patients with
      central and peripheral vestibular disorders of various aetiologies. Also
      influence of antihomotoxic remedies on sacculo-collic reflex function were
      followed. Treatment concerned 23 ills that is 20 women and 3 men in age from 20
      to 68 years, average age being 46,82 years. The studied population included 8
      patients were diagnosed to have Meniere's disease, 5 ills suffered from
      neuronitis vestibularis, 5 patients complained of vertigo of vertebrobasilar
      arterial insufficiency. 3 patients were diagnosed to have vertigo after head
      trauma, 1 patient suffered from benign paroxysmal positional vertigo and one's
      cause of disease was unknown. Patients with tumor of ponto-cerebellaris angle or
      VIII nerve were excluded. Registration of VEMPs was done in all patients treated
      before starting and after stopping therapy. After using of Cerebrum comp.
      improvement of vestibulo-spinal reflex function was affirmed in the form of
      shorted latencies and higher amplitudes of VEMPs in the most patients. Using
      sublingually of Vertigoheel distinct greater amplitudes were observed in
      significant numbers of patients after therapy. Administered of placebo did not
      essential influence on values of VEMPs parameters.

PMID- 10917062
TI  - [First experiences in Neural Response Telemetry in patients with Nucleus 24
      cochlear implant system].
AB  - Nucleus 24 Cochlear Implant System enables bidirectional communication with the
      implant-telemetry. Information about implant function can be obtained using
      telemetry. Neural Response Telemetry is a measurement of neural activity in the
      cochlea as a response to electrical stimulation. Principle of NRT recording,
      classification of responses and examples of responses obtained in patients
      implanted in Poznan are presented.

PMID- 10917063
TI  - [Phoniatric rehabilitation in patients with recurrent laryngeal nerve paralysis
      after thyroid gland surgery].
AB  - The authors have presented methods of treatment in patients with recurrent
      laryngeal nerve paralysis after thyroid surgery including pharmacology,
      physiotherapy, phoniatric rehabilitation and phonosurgery.

PMID- 10917064
TI  - [Metastasis of papillary thyroid carcinoma resembling the cervical lateral cyst].
AB  - Cystic neck mass, enlarging for many years, as the first symptom of occult
      thyroid carcinoma was presented. On the basis of clinical and ultrasonographical
      examination the initial diagnosis was made: bronchiogenic neck cyst. The
      metastases of papillary carcinoma of thyroid gland were recognized in
      histological examination. The patient was admitted for surgical treatment.

PMID- 10917065
TI  - [An unusual case of the otogenic purulent thrombosis of the sigmoid sinus and
      internal jugular vein].
AB  - The authors present a case of 51 years old female suffering from the purulent
      thrombophlebitis of the sigmoid sinus and internal jugular vein. The disease
      developed in the course of chronic otitis media. During first 2 weeks she was
      treated with antibiotics because of the septic fever without significant otogenic
      symptoms. An incidental otolaryngologic examination showed the reason of the
      illness. The authors emphasise the thrombophlebitis process extended from
      transverse sinus to the lower end of internal jugular vein. Nowadays the otogenic
      thrombophlebitis complications are rare, but the knowledge of them is
      indispensable in the everyday practice. The authors emphasise the necessity of
      cooperation otolaryngologists with other specialists. Especially it is important
      in the Polish new model of health service, which place the main role of the
      treatment to general practitioners.

PMID- 10917067
TI  - [Clinical and histopathological examinations in the allergic rhinitis].

PMID- 10917066
TI  - [Meningiomas of the nose and paranasal sinuses].
AB  - In material of ENT Department, Medical University of Gdansk we have three cases
      of extracranial meningioma localized in the nose and sinuses. Two of them are
      presented in this paper. One case was 29 year woman with meningioma of the nose
      and ethmoid and maxillary sinuses; it was residual tumor after removal of
      intracranial meningioma 3 years earlier. Second case was 14 year boy with
      meningioma of the nose, ethmoid and maxillary sinuses and of the orbit. In both
      patients tumor was removed by rhinosurgical access (lateral rhinotomy). Late
      results of the operation were very good. Basing on clinical and radiological
      pictures of both cases, pathological characteristics of naso-sinusal meningioma
      was made.

PMID- 10917068
TI  - [The estimation of usefulness of some acute phase proteins evaluation in
      monitoring otitis media among children].

PMID- 10917071
TI  - Chronic vaginal candidiasis. Management in the postmenopausal patient.
AB  - Vulvovaginal candidiasis (VVC) is a cause of significant morbidity in many women
      of a childbearing age worldwide. There is a paucity of literature on the
      prevalence of this condition in postmenopausal women, although it is believed to
      be uncommon because of the estrogen dependence of VVC. Postmenopausal women who
      have underlying risk factors for VVC (e.g. hormone replacement therapy,
      uncontrolled diabetes mellitus, immunosuppression caused by medication or
      disease) may be at risk of chronic or recurrent VVC. However, as in younger
      women, it is likely that, even after exhaustive investigations, no cause will be
      found in a significant number of patients. The investigation and treatment of VVC
      in older women should be the same as that undertaken in younger women. Both
      topical and oral preparations are available, but oral regimens are perhaps more
      acceptable because of the ease of administration and avoidance of potentially
      messy creams and suppositories. Ketoconazole at a dosage of 400 mg daily for 14
      days can be used to achieve clinical remission of symptoms and negative fungal
      cultures. Induction treatment should be followed by maintenance therapy for 6
      months with ketoconazole 100 mg daily, itraconazole 50 to 100 mg daily or
      fluconazole 100 mg weekly or 150 mg monthly. Short courses of topical therapy,
      e.g. 500 mg clotrimazole pessaries as a single weekly dose for 6 months or 100mg
      miconazole pessaries twice weekly for 3 months, followed by once weekly for 3
      months may also be used.

PMID- 10917069
TI  - Prospects for vaccination in prostate cancer.
AB  - Prostate cancer continues to be a major cause of morbidity and mortality.
      Surgical and medical management of the disease has improved but there is little
      effect upon overall survival. Novel therapies such as immunotherapy offer the
      potential of treating the disease by stimulating the immune system to mount a
      response to the cancer systemically. This review highlights the pitfalls and
      progress in the understanding of the role of the immune system in malignancy and
      also explains the theory behind prostate cancer vaccine trials.

PMID- 10917070
TI  - Colon cancer: a role for cyclo-oxygenase-2-specific nonsteroidal anti
      inflammatory drugs.
AB  - Large bowel cancer is not only the third most frequent cancer in the world but is
      one of the most common human malignancies in Western countries, including North
      America. In recent years, multidisciplinary research in epidemiology, molecular
      biology, and laboratory animal model studies have contributed much to our
      understanding of the aetiology of this cancer; more importantly, it has enabled
      us to devise preventive strategies. Several epidemiological studies have detected
      a 40 to 50% decrease in risk of colorectal cancer in individuals who regularly
      use aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). Clinical
      trials with NSAIDs in patients with familial adenomatous polyposis have
      demonstrated that treatment with NSAIDs caused regression of pre-existing
      adenomas. Preclinical efficacy studies have provided scientifically sound
      evidence as to how NSAIDs act to retard, block, or reverse colonic
      carcinogenesis. Equally exciting are opportunities for effective chemoprevention
      with selective cyclo-oxygenase-2 inhibitors in a variety of animal models of
      colon cancer. Selective cyclo-oxygenase-2 inhibitors such as celecoxib have been
      proven to be effective chemopreventive agents against colonic carcinogenesis with
      minimal gastrointestinal toxicity. Our exploration of the multistep process of
      carcinogenesis has provided substantial insights into the mechanisms by which
      anti-inflammatory agents modulate these events. There is growing optimism for the
      view that realisation of preventive concepts in large bowel cancer will also
      serve as a model for preventing malignancies of the prostate and breast.

PMID- 10917072
TI  - Proper use of antiarrhythmic therapy for reduction of mortality after myocardial
      infarction.
AB  - In this review, we summarise Vaughan Williams' classification of antiarrhythmic
      agents and the trials that have explored their efficacy in reducing mortality
      after myocardial infarction (MI). After analysing the data, it is clear that
      there is no role for class I antiarrhythmic agents as prophylaxis after MI since
      their use has been associated with increased mortality. Class II agents, i.e.
      beta-blockers, have demonstrated a reduction in mortality in combined and
      individual trials which extended for up to 6 years after the initial event. The
      class III drug, d,l-sotalol has been shown to have possible benefit, whereas its
      isomer without any beta-blocking properties, dexsotalol, has been shown to
      increase the incidence of arrhythmias. Amiodarone appears to reduce the incidence
      of deaths due to arrhythmia and sudden deaths without changing overall mortality.
      As a group, the calcium antagonists, class IV agents, have not been shown to
      reduce mortality and, in the case of nifedipine, may even increase it. Verapamil
      has been shown to be beneficial in one large study and may have a role in those
      patients in whom the use of beta-blockers is contraindicated. At this time, we
      recommend early implementation of beta-blockers for all patients without
      contraindications after MI. Further studies evaluating implantable defibrillators
      as primary and secondary prevention have provided significant risk reductions in
      certain high risk patient subsets. Future efforts will need to focus on more
      accurate risk stratification of post-MI patients and the role of both
      defibrillators and, possibly, amiodarone in improving survival.

PMID- 10917073
TI  - Heparin-Induced thrombocytopenia: minimising the risks in the elderly patient.
AB  - Heparin therapy may sometimes be seriously complicated by heparin-induced
      thrombocytopenia (HIT). Heparin use for treatment and prevention of
      thromboembolism is more common in the elderly and that may be the reason why HIT
      is reported more frequently in this group of patients. The first approach in the
      management of HIT is awareness of this disorder. The morbidity and mortality
      associated with HIT may be reduced by avoiding unnecessary heparin exposure, by
      reducing the duration of heparinisation and by using low molecular weight
      heparins rather than unfractionated heparin. A decrease from baseline values of
      at least 30% in the platelet count, any unexplained thrombotic event and the
      finding of a white clot at thrombectomy are clinical warning signs that should
      alert physicians to a possible diagnosis of HIT. Indeed, early clinical
      recognition of HIT may sometimes prevent the severe complications associated with
      this disorder. Objective confirmation of the diagnosis of HIT is difficult
      because none of the available biological tests possess 100% sensitivity or 100%
      specificity. It is, however, possible to optimise the performances of the
      functional assay, mainly the platelet aggregation test (PAT), by following the
      manoeuvres described by differ- ent investigators. The use of 2 classes of assay
      (functional and antigen assays) and repeat testing on another day can avoid
      misdiagnosis of HIT. An alternative parenteral anticoagulant treatment is most
      often mandatory after heparin withdrawal. Danaparoid sodium and lepirudin are 2
      drugs that are currently available for the treatment of HIT, and the efficacy of
      argatroban needs to be confirmed in greater numbers of patients with HIT. The use
      of these drugs has contributed to the reduction in the mortality and morbidity
      associated with HIT.

PMID- 10917075
TI  - Silent myocardial ischaemia in the elderly.
AB  - Coronary artery disease (CAD) is a leading cause of death and disability in the
      elderly. Several recent studies have shown that silent myocardial ischaemia (SMI)
      is a common manifestation of CAD, especially in the elderly. As many as 40% of
      elderly patients with no prior history of CAD may have underlying asymptomatic
      disease and up to 50% of elderly patients with known CAD might have evidence of
      SMI. The results of studies in elderly patients with CAD have also shown that SMI
      might exist despite antianginal therapy that is considered adequate for symptom
      control. In order to diagnose such residual SMI, the clinician would need to
      perform 24- to 48-hour Holter monitoring in the ambulatory setting while the
      patient is performing routine daily activities. Although a number of anti
      ischaemic drugs have been evaluated for the treatment of SMI, available data
      suggest that beta-blocker given alone or in combination with a nitrate compound
      or calcium antagonist provides the best therapeutic choice. The long term benefit
      of SMI suppression in elderly patients has not been established. Future studies
      need to evaluate the clinical benefits of therapy given for SMI in the elderly.

PMID- 10917076
TI  - The rise of clinical leadership in New Zealand: towards clinical governance.

PMID- 10917074
TI  - Role of dopamine in learning and memory: implications for the treatment of
      cognitive dysfunction in patients with Parkinson's disease.
AB  - Along with dementia, Parkinson's disease (PD) is associated with subtle but
      widespread cognitive impairment even in the absence of clinically apparent
      cognitive decline. Many of the deficits are reminiscent of those observed in
      patients with lesions of the prefrontal cortex, that is, failure in executive
      function that involves skills required for anticipation, planning, initiation and
      monitoring of goal-directed behaviours. This paper reviews the dopaminergic brain
      circuitry, and preclinical and clinical evidence supporting the regulation of
      prefrontal cortex activity by dopamine, and the role of dopamine in cognitive
      impairment in patients with PD. It addresses the need to integrate these facts
      and the findings of positive, neutral or detrimental frontal cognitive response
      to dopaminergic drugs in PD which should be viewed mainly in the context of
      methodological differences for subject selection. The cognitive effect of
      levodopa does not much depend on a neuropsychological specificity of the drug,
      the years of evolution of the disease or the severity of the motor signs.
      Instead, it may be a function of the level of dopamine depletion in different
      parts of the basal ganglia and prefrontal cortex. Consequently, dopaminergic
      agents may enhance cognitive functions in some patients and impair them in
      others. De novo patients tend to improve during the first year of treatment;
      stable responders to oral levodopa tend to show no changes; and wearing-off
      responders tend to deteriorate with acute levodopa challenge. Enhancement and
      impairment of cognitive function with dopaminergic treatment is incomplete and
      task-specific, suggesting the need to integrate the above dopamine facts with
      other neurotransmitter systems findings in PD. Meanwhile, such cognitive
      dissociation can be useful in refining the definition of the cognitive deficit in
      PD patients without dementia and emphasising the need to develop new and specific
      strategies for treatment.

PMID- 10917077
TI  - Prevalence, severity and associated features of gastro-oesophageal reflux and
      dyspepsia: a population-based study.
AB  - AIMS: To describe the prevalence and severity of dyspepsia and gastro-oesophageal
      reflux in the community, to investigate their association with lifestyle factors
      and to evaluate the consultation pattern for these conditions. METHOD: A
      previously validated questionnaire was posted to 1000 adults randomly selected
      from the electoral rolls of the greater Wellington region. It investigated
      symptoms of dyspepsia, reflux, lifestyle and consultation pattern over the
      previous twelve months. RESULTS: Response rate was 81.7%. Prevalence of dyspepsia
      was 34.2%. Prevalence of reflux was 30%. The overall prevalence of both symptom
      groups combined was 45.2%. Most subjects had multiple symptoms. Results indicated
      63% of subjects with reflux also had symptoms of dyspepsia and 56% of subjects
      with dyspepsia showed symptoms of reflux. Although 69% of subjects with heartburn
      used over-the-counter medications, only 17% consulted medical practitioners.
      Current and ex-smokers had a higher prevalence of reflux. Dyspeptic symptoms were
      not associated with alcohol intake or aspirin use. Prevalence of dyspeptic
      symptoms did not change with increasing age. CONCLUSIONS: Dyspepsia is very
      common in the community. Significant overlap among the subgroups of dyspepsia
      makes a classification, based on symptoms alone, of questionable value. Frequency
      and severity of symptoms should be incorporated in the definition to exclude
      those subjects with trivial symptoms.

PMID- 10917078
TI  - Audiological screening of neonatal intensive care unit graduates at high risk of
      sensorineural hearing loss.
AB  - AIM: To audit the identification and screening of graduates from a neonatal
      intensive care unit with risk factors for sensorineural hearing loss. METHODS:
      Hospital medical records of newborn infants discharged from the neonatal
      intensive care unit, Christchurch Womens Hospital, between 1 July 1994 and 30
      June 1995 (n=564), were examined to identify those at risk for sensorineural
      hearing loss according to the American Speech-Language Hearing Association risk
      criteria 1991. Auditory brainstem response test results were obtained from the
      Christchurch Hospital Audiology Department. Outcome measures were: presence of
      hearing loss risk factors, numbers tested with auditory brainstem response, age
      at test and presence and degree of hearing impairment. RESULTS: Of 5,215 live
      births in Christchurch, 564 infants were discharged through the neonatal
      intensive care unit. Of these, 86 had risk factors for sensorineural hearing
      loss. There were 72 (84%) infants tested at audiology, with fifteen (17%) having
      abnormal test results. There were fourteen with risk factors who did not get
      audiology screening. CONCLUSION: A high proportion (84%) of high risk newborn
      infants had auditory brainstem response testing. Further improvement would
      require strict implementation of standard procedures. Auditory brainstem response
      screening is part of a wider population surveillance approach to identify hearing
      loss as early as possible.

PMID- 10917080
TI  - Learning by distance for general practitioners: students' experiences of
      Goodfellow Unit diplomas.
AB  - AIM: To examine students' reasons for studying and their learning experiences in
      the Goodfellow Unit postgraduate distance learning diplomas. METHOD: A survey was
      sent to all students currently enrolled in the Goodfellow Unit diplomas in
      emergency, sports and geriatric medicine. RESULTS: The response rate was 63%.
      Students had enrolled to gain more skills on their present job for personal
      satisfaction or for personal interest. Students reported difficulties in fitting
      study into already busy lives, but general satisfaction with the learning format
      of videotaped lecture sessions plus written study guides. They also reported
      having to develop a different method of learning from their undergraduate study
      methods. Students predicted a number of ways of improving learning outcomes.
      CONCLUSION: Distance learning is a viable option for busy general practitioners,
      as long as it can be self paced, practical and relevant to the work situation.

PMID- 10917079
TI  - Assessing the accuracy of hospital admission and discharge diagnosis of traumatic
      brain injury in a New Zealand hospital.
AB  - AIMS: To investigate the accuracy of admission and discharge coding of traumatic
      brain injury (TBI) in a New Zealand hospital. METHOD: Prospective study of all
      patients over fifteen years of age admitted to Hutt Hospital over a six-month
      period with an actual or potential diagnosis suggesting TBI. RESULTS: During the
      six month period of study, 65 patients with the diagnosis of TBI were admitted to
      Hutt Hospital. Of these, 21 (32.3%) met the criteria for diagnosis of TBI
      ('Definite TBI'). A further eighteen patients, not admitted with a diagnosis of
      TBI, met the TBI criteria. Only 14/39 (35.9%) of 'Definite TBI' cases were
      identified at both admission and discharge. Discharge diagnosis of TBI identified
      correctly 26/39 (66.7%) of definite cases, with 34/60 (56.7%) cases with a
      discharge diagnosis of TBI not meeting our criteria for the diagnosis of TBI. Six
      out of 39 'Definite TBI' cases (15.4%) were not identified by either admission or
      discharge diagnosis. Thirty of the 65 patients (46.2%) admitted to hospital with
      the diagnosis of TBI showed clinical evidence of having taken alcohol, although
      only 12 had blood alcohol concentration measured. CONCLUSIONS: The admission and
      discharge diagnoses of TBI were not accurate when compared to a standard
      definition of TBI. For hospital discharge data to have any value, agreement on an
      operational diagnosis of TBI needs to be made, which should include measurement
      of the blood alcohol concentration. A suggestion for a diagnostic strategy is
      presented, along with ICD-10-AM codes that could be used to improve the current
      situation.

PMID- 10917081
TI  - Does infection have a role in the pathogenesis of coronary artery disease?

PMID- 10917082
TI  - The label 'Occupational Overuse Syndrome': time to change.

PMID- 10917083
TI  - Report of workshop--red meat and colorectal cancer.

PMID- 10917084
TI  - Oral contraceptives and venous thromboembolism. New Zealand Committee, RANZCOG.
      Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

PMID- 10917085
TI  - Oral contraceptives and venous thromboembolism--again.

PMID- 10917086
TI  - What isn't medical practice?

PMID- 10917087
TI  - American Cup mania?

PMID- 10917088
TI  - Tobacco tax and Maori and low-income families.

PMID- 10917089
TI  - Air pollution.

PMID- 10917090
TI  - The use of pedicled expanded flaps for aesthetic resurfacing of the burned face.
AB  - Reconstruction of extensive, deep burns of the face is a challenging problem in
      plastic surgery. The authors report the use of tissue expanders placed in the
      upper chest for facial resurfacing after burn injuries in 4 patients. The
      expanders are hyperinflated. The flap is then advanced upward to resurface an
      aesthetic unit of the face with the pedicle intact. The pedicle is divided 2
      weeks later. The method of reconstruction allows a large area of facial
      resurfacing to be performed without fear of flap loss or flap retraction
      impairing the cosmetic result. This technique has the disadvantage of being a
      staged procedure and cannot be performed in those with burns of the upper chest.

PMID- 10917091
TI  - The use of pedicled perforator flaps for reconstruction of lumbosacral defects.
AB  - Large lumbosacral defects remain a difficult challenge in reconstructive surgery,
      especially in the nonparaplegic patient. Traditional options for closure include
      local rotation or transposition flaps and musculocutaneous flaps. These flaps,
      however, are not an optimal option in previously irradiated or operated areas, or
      in cases of large defects. Application of the perforator principle to the
      traditional musculocutaneous flap creates perforator flaps, which are an
      additional tool in the treatment of these defects in the nonparaplegic patient. A
      large amount of healthy, well-vascularized tissue can be transferred on one
      perforator without sacrificing important underlying muscles. The arc of rotation
      is also larger than in traditional flaps. The authors present an anatomic
      overview of three types of pedicled perforator flaps: the superior gluteal artery
      perforator flap, the lumbar artery perforator flap, and the intercostal artery
      perforator flap. They also report 4 patients in whom a pedicled perforator flap
      was used to reconstruct a large lumbosacral defect.

PMID- 10917092
TI  - Abdominal recovery after laparotomy and omental transposition into a grossly
      contaminated median sternotomy wound.
AB  - Grossly contaminated median sternotomy wounds are frequently treated with
      transposed omental flaps. A laparotomy adjacent to such an infected wound carries
      the risk of peritonitis. It has been suggested that this risk may increase when
      the omentum, which has anti-infective properties, is removed from the abdominal
      cavity and is transposed to the chest. The authors evaluated abdominal recovery
      after laparotomy and omental transposition into an adjacent, grossly contaminated
      median sternotomy wound. The study group included 15 patients who had sternal
      wound reconstruction with an omental flap between 1990 and 1998. All patients
      underwent median sternotomy reconstruction according to a "two-compartment"
      operative sequence protocol, which included division of the surgical field into
      an upper (thoracic) contaminated zone and a lower (abdominal) clean zone. The
      control group was comprised of 15 patients who underwent elective laparotomy for
      splenectomy during the same time period. The effect of the surgical procedure on
      the abdomen was compared between the two groups. The timing of the reappearance
      of peristalsis and regular bowel function, and the incidence of bowel obstruction
      and postoperative peritonitis were similar in the two groups. The findings
      indicate that laparotomy and omental transposition in the presence of a grossly
      contaminated median sternotomy wound is a safe procedure, and is associated with
      a low rate of abdominal complications.

PMID- 10917093
TI  - Anterior oblique ligament reconstruction of the thumb using the transverse carpal
      ligament: description of a new procedure.
AB  - Traumatic dislocation of the thumb carpometacarpal joint is an uncommon injury
      that may have long-term sequelae after treatment. Joint instability may cause
      pain, weakness of pinch, and the increased likelihood of development of
      posttraumatic arthritis. The anterior oblique ligament has generally been
      accepted as the most important static stabilizer of the trapeziometacarpal joint.
      Numerous operative techniques have been described to reconstruct this ligament.
      The author introduces a novel operative procedure to reconstruct the anterior
      oblique ligament of the thumb using the transverse carpal ligament (AOLR-T). This
      procedure was performed on 5 fresh-frozen cadaveric hands to assess its
      feasibility and potential efficacy. No technical difficulties were encountered.
      AOLR-T may be indicated for the treatment of thumb carpometacarpal instability of
      primary or secondary etiology and may avoid many of the disadvantages of
      traditional ligament reconstruction.

PMID- 10917094
TI  - Fingertip reconstruction using two variations of direct-flow homodigital
      neurovascular island flaps.
AB  - The fingertip is an extremely intricate area of digital sensibility that plays an
      important role in fine perception and hand function. Thus, sensate fingertip
      reconstruction is essential to the recovery of most hand functions. The authors
      used two methods of direct-flow homodigital neurovascular island flap coverage to
      reconstruct distal finger amputations-namely, the triangular-advancement flap
      technique and the step-advancement flap method. The authors present their
      experience with these two variations of direct-flow homodigital neurovascular
      island flaps and their use in reconstructing 18 fingertips and 7 proximal
      amputation stumps. They did not observe flap failure, and they achieved stable,
      well-vascularized, appropriate-thickness skin coverage with good sensory
      properties in all patients. However, they found that the triangular-advancement
      flap technique was easier to plan and perform than the step-advancement method.

PMID- 10917095
TI  - Verrucous malformations: their presentation and management.
AB  - Verrucous hemangiomas are a distinct subset of vascular malformations that have
      not been described extensively in the plastic surgery literature. They are
      characterized by reactive epidermal acanthosis, papillomatosis, hyperkeratosis,
      and extension into the subcutaneous tissues. In response to injury, infection, or
      subtotal resection, they enlarge and become increasingly keratotic. In light of
      contemporary definitions of hemangiomas and malformations, the authors
      recommended that these lesions be renamed verrucous malformations. The authors
      review their evaluation and treatment of 6 patients with this lesion and offer an
      algorithm that emphasizes excision over ablative therapy. Of the 6 patients, 3
      patients had failed either cryotherapy or laser removal by a nonsurgeon, with a
      consequent increase in lesion size and discomfort. The lesions were all
      subsequently excised. Because of the size and location of the verrucous
      malformations, staged removal was required in 3 patients. Patients have been
      followed for as long as 7 years. A single recurrence was controlled with
      reexcision. Excision of verrucous malformations, rather than laser ablation or
      cryosurgery, is supported by the authors' favorable results.

PMID- 10917096
TI  - Prevention of meatal stenosis with W-flap glanuloplasty in hypospadias surgery: a
      long-term follow-up.
AB  - Meatal stenosis is a complication that can occur after hypospadias surgery.
      Although there are many different surgical techniques that can solve this
      problem, once it has occurred, meatal stenosis can be difficult to treat. To
      decrease meatal stenosis risk and to achieve an anatomically placed,
      aesthetically pleasing meatal opening, a new W flap was designed for
      glanuloplasty. The authors describe the technique in detail along with long-term
      results. A total of 356 hypospadias cases were operated using various
      urethroplasty methods. Independent from the preferred urethroplasty method, the W
      flap was used for glanuloplasty in all patients. Patients were followed for 1 to
      10 years. Meatal stenosis incidence was 0.8%, and good cosmetic results with a
      natural-looking, anatomically placed meatus and a well-directed urinary stream
      during urination were achieved. W-flap glanuloplasty, an addition to
      reconstructive surgeons' armamentarium, is applicable to most patients. It places
      the meatus in its appropriate anatomic location, increases the meatal diameter by
      insetting two flaps, avoids a circular anastomosis, reduces the risk of late
      contraction, helps to achieve good aesthetic results with good urinary stream,
      eliminates the need for stents, and reduces meatal stenosis risk overall. It is a
      good glanuloplasty alternative that can be applied with most hypospadias repair
      techniques.

PMID- 10917097
TI  - Effect of the delay phenomenon in the rat single-perforator-based abdominal skin
      flap model.
AB  - During the last decade, innovations in reconstructive surgery have presented a
      new type of flap called the "perforator-based flap." Perforator-based flaps
      became useful alternatives for solving difficult problems. In the authors'
      previous study, they created a single musculocutaneous perforator-based abdominal
      skin flap. In their current study they evaluate the effect of various surgical
      delay procedures on this model. They divided 32 Sprague-Dawley rats equally into
      four groups (one control group and three delay groups). Three different delay
      procedures were employed in the delay groups. In one group, only the flap
      boundaries were incised (delay group 1). In the other delay groups, flap
      boundaries were incised and the contralateral (opposite side of the pedicle,
      delay group 2) or ipsilateral (pedicle side, pedicle left intact; delay group 3)
      musculocutaneous perforators were ligated. The period of delay was 1 week in all
      groups. After 1 week, a single-perforator-based abdominal skin flap was elevated
      as in the control group. One week after the final procedure, surviving skin areas
      were calculated and microangiograms were acquired. The mean surviving skin area
      was 75% +/- 3% (standard deviation) in the control group, 97% +/- 3% in delay
      group 1, 81% +/- 6% in delay group 2, and 96% +/- 3% in delay group 3. Delay
      group 2 showed substantial necrosis 1 week after the delay procedure and was thus
      excluded from the study. Results were analyzed using one-way analysis of
      variance, and post hoc analyses were performed using Tukey's multiple comparison
      test. The authors observed the advantages of the delay phenomenon in the two
      delay groups (p < 0.05). Microangiograms were examined grossly, and a marked
      difference between the two delay groups and the control group was observed. Many
      dilated choke vessels were seen in delay groups 1 and 3. Incising the flap
      boundaries with or without ligating the ipsilateral perforators (keeping the
      pedicle intact) 1 week before harvesting single-perforator-based abdominal skin
      flaps in the rat results in a delay effect. Conversely, incising the flap
      boundaries and ligating the contralateral perforators have no delay effect in
      this model.

PMID- 10917098
TI  - The role of periosteum and different dissection types on callus formation:
      quantitative analyses with scintigraphy in a rabbit mandible model.
AB  - In this experimental study, the effects of different dissection types and the
      role of the periosteum on callus formation were investigated. Forty-five rabbits
      were divided into three groups of 15 rabbits. In the first group, a classic
      subperiosteal dissection was performed to reach the mandible. In the second
      group, the dissection was done extraperiosteally between the periosteum and the
      muscle. In the third group, the periosteum at the osteotomy line was stripped out
      bilaterally both on the lingual and the buccal sides (1.5 cm wide on each side).
      In all groups, linear vertical osteotomy was performed using an oscillating saw,
      and fracture fragments were fixed with surgical wire. The animals were evaluated
      using biomechanical (traction test), histological, and scintigraphic methods. The
      most durable callus in the traction test and, scintigraphically, the most rapid
      remodeling were seen in the second group. The histological study performed during
      week 3 revealed immature callus formation in the first and second groups, and no
      such formation in the third group. At week 8 the callus was mature in the first
      two groups and in the third group it was seen but not mature.

PMID- 10917099
TI  - Secondary venous ischemic injury associated with neutrophil infiltration and
      lipid peroxidation: amelioration of injury by cyclosporin A in a rat inguinal
      island flap.
AB  - Secondary venous ischemia caused by anastomotic failure is one of the major
      causes of failure after free tissue transfers and replantations. The effects of
      cyclosporin A (CsA) on secondary ischemic injury associated with neutrophil
      infiltration and lipid peroxidation were evaluated in a rat inferior epigastric
      island skin flap model. Primary ischemia was produced by arteriovenous occlusion
      for 2 hours. Twenty-four hours later, secondary venous ischemia was produced by 5
      hours of venous occlusion. Nonischemic (n = 5), primary ischemic (n = 5), and
      secondary ischemic control groups (n = 10), and four treatment groups (n = 10)
      were created. Treatment groups received either 15 or 30 mg per kilogram per day
      oral CsA for 3 days before flap elevation, or 15 or 30 mg per kilogram
      intravenous CsA at 4 hours of secondary venous ischemia. Flap survival area,
      malondialdehyde (MDA) content, and myeloperoxidase (MPO) activity were assayed
      for each group. The mean flap survival area of the high-dose posttreatment group
      was significantly higher than the secondary ischemic control group (29% +/- 39%
      vs. 3% +/- 8%; p < 0.05, Student's t-test). The MDA and MPO levels of each
      treatment group were significantly lower than the secondary ischemic control
      group at hours 1 and 24 (p < 0.0001, Student's t-test). The lowest MDA and MPO
      levels were achieved in the high-dose posttreatment group. Results suggest that
      CsA may improve flap survival after secondary venous ischemia by attenuating
      neutrophil infiltration and by reducing lipid peroxidation.

PMID- 10917100
TI  - Elongated uvula with a pleomorphic adenoma: a rare cause of obstructive sleep
      apnea syndrome.
AB  - The authors encountered a case of elongated uvula with a pleomorphic adenoma
      originating from the minor salivary gland, causing frequent upper airway
      obstruction. A 75-year-old woman had obstructive sleep apnea syndrome brought
      about by the swallowing impact of the pendulous tumor into the hypopharyngeal and
      supralaryngeal spaces. Although there are some case reports about tumors
      originating from the uvula, this is the first reported to cause obstructive sleep
      apnea syndrome.

PMID- 10917101
TI  - Pneumomediastinum after injection injury to the hand.
AB  - Pneumomediastinum as a consequence of injection injury to the hand has not been
      previously reported. We present a 22-year-old male who developed
      pneumomediastinum when a high pressure hose injected air into his hand. The
      anatomic continuity between peripheral ulnar neurovascular bundle and the hilar
      vessels provided the route for air entering the hypothenar eminence to penetrate
      the mediastinum. After ruling out life-threatening causes of pneumomediastinum
      such as esophageal perforation, his management included observation and serial
      radiographs. By one week there was complete resolution of the mediastinal air.
      This report demonstrates that pneumomediastinum may be associated with air
      injection injury of the hand, and that expectant management is appropriate.

PMID- 10917102
TI  - A modified reversed digital island flap incorporating the proper digital nerve.
AB  - A standard reversed digital artery flap is based on the digital artery and vena
      comitantes alone, leaving the proper digital nerve intact. In the authors'
      opinion, in situations in which the fingertip pulp is lost completely, it is
      unnecessary to leave the nerve in situ. Using their technique, the proper digital
      nerve is included in the pedicle. The pedicle is raised as a monobloc of fatty
      tissue containing the small veins important for drainage. The proper digital
      nerve in the flap is sutured to the stump of the opposite proper digital nerve.
      They found this flap to be very reliable, and quite easy and quick to raise. A
      patient is presented and discussed in detail.

PMID- 10917103
TI  - Functional lip reconstruction with a radial forearm free flap combined with a
      masseter muscle transfer after wide total excision of the chin.
AB  - Total lower lip reconstruction was accomplished by combining a radial forearm
      free flap with a masseter muscle transfer. The patient, who had T4 carcinoma, had
      the entire lower lip resected including the depressor anguli oris muscle. A
      radial forearm flap was used to reconstruct the lower lip lining and the floor of
      the oral cavity. The right and left masseter musculofascial flaps were elevated
      and transferred in the medial-superior direction, and the peripheral margins of
      the flaps were sutured together. The lateral margins of the flaps were then
      sutured to the orbicularis oris muscle of the upper lip. Good sphincter function
      was obtained more than 1 year after the operation, electromyography revealed
      almost normal mobility of the transferred masseter muscles, and no sagging of the
      masseter muscle sling was observed. This procedure appears to be effective for
      the reconstruction of sphincter function of the lower lip after wide excision of
      the entire chin.

PMID- 10917104
TI  - Malignant fibrous histiocytoma arising in a thoracotomy scar.
AB  - Malignant fibrous histiocytoma arises most commonly de novo and rarely from sites
      of chronic inflammation. The authors present a case of malignant fibrous
      histiocytoma arising in a thoracotomy hypertrophic scar. The patient required
      large local excision of the tumor down to and including the muscle layer with
      postoperative radiation treatment. Factors associated with the occurrence of this
      sarcoma are discussed along with salient management principles.

PMID- 10917105
TI  - Metastatic basal cell carcinoma of the axilla: report of a case and
      reconstruction with an island lateral pectoral flap.
AB  - A case of metastatic basal cell carcinoma arising from the skin of the axilla is
      reported. Multiple surgical procedures performed previously for recurrences of
      basal cell carcinoma limited the availability of conventional local flaps in the
      reconstruction of the axillary defect after excision of the recurrent tumor and
      axillary nodal dissection. The use of an island flap based on the lateral
      pectoral vessels and lateral cutaneous branches of the intercostal vessels is
      described.

PMID- 10917106
TI  - Advances in the biology of zone II flexor tendon healing and adhesion formation.
AB  - There has been dramatic improvement in the results of zone II tendon surgery in
      the last three decades. This improvement was brought, to a great extent, by the
      better understanding of the mechanisms of tendon healing. This article provides
      an overview of the mechanism of intrasynovial tendon healing, the role and origin
      of fibroblasts, and the effects of extracellular components and various growth
      factors on tendon healing. It also sheds light on the incidence and significance
      of tendon adhesions. An account of the ultrastructure of the synovial sheath is
      presented.

PMID- 10917107
TI  - A new test for superficialis flexor tendon function.
AB  - Diagnosis of flexor digitorum superficialis tendon injury is difficult if the
      profundus tendon functions properly. A new test, called the DIP extension test,
      to diagnose isolated flexor digitorum superficialis tendon injuries is described.
      The test is particularly useful for the index finger. During the test the patient
      is asked to flex the proximal interphalangeal joint of the injured finger while
      this finger is in a precision pinch position with the thumb. The distal
      interphalangeal (DIP) joint normally has to go in hyperextension after this
      action. Inability to hyperextend the DIP joint confirms a superficialis tendon
      injury. Fifteen isolated superficialis tendon injuries in 10 patients were
      evaluated with the DIP extension test. Nine of these patients were later explored
      and the diagnosis was confirmed in all patients.

PMID- 10917108
TI  - Free transfer of the radial forearm flap with preservation of the radial artery.
AB  - One of the main disadvantages of the radial forearm flap is the sacrifice of a
      major artery. To overcome this drawback the authors describe a technique of free
      transfer of the flap with preservation of the radial artery. The flap is elevated
      as a distal row perforator-based fasciocutaneous flap with a very short segment
      of the radial artery included in the inverted-T-shaped arterial pedicle. The
      venous outflow of the flap is provided by the cephalic vein, with accompanying
      veins of the radial artery left behind. Although the donor radial artery is
      repaired primarily, the flap is transferred to reconstruct a soft-tissue defect
      resulting from the release of a neck contracture after radiotherapy in a 42-year
      old patient who had previous excision of a mandibular osteosarcoma. The arterial
      anastomosis was performed end to end between the superior thyroid artery and one
      limb of the arterial pedicle, with the other limb ligated. The venous anastomosis
      was performed end to end between the cephalic vein and the external jugular vein.
      The flap survived completely and a satisfactory result was obtained. The radial
      artery is demonstrated to be patent long after surgery, both with Allen's test
      and with a Doppler examination. Considering the possible sequelae of the
      sacrifice of the radial artery, this technique is obviously advantageous to such
      patients, even with a nonsatisfactory preoperative Allen's test. This perforator
      based radial forearm flap is very easy to raise and to transfer, with anastomoses
      of large-diameter vessels.

PMID- 10917109
TI  - Distally based superficial peroneal neuroadipofascial turnover flap for dorsal
      foot reconstruction.

PMID- 10917111
TI  - Superior and inferior ulnar collateral arteries originating as a common trunk in
      the arm.

PMID- 10917110
TI  - Malignant clear cell hidradenoma with giant metastasis to the axilla.

PMID- 10917112
TI  - In the fullness of time.

PMID- 10917113
TI  - A new technique for performing a laparoscopic hysterectomy using
      microlaparoscopy: microlaparoscopic assisted vaginal hysterectomy (mLAVH).
AB  - In an effort to further decrease patient postoperative scarring and discomfort, a
      new technique of microlaparoscopic assisted vaginal hysterectomy is employed.
      Using a 2-mm lateral port, a single infraumbilical port for the power source, and
      a 3-mm or 5-mm suprapubic port for aid in manipulation, seven consecutive
      patients underwent hysterectomy without complication and had rapid return to
      their daily activities.

PMID- 10917114
TI  - Delayed oral estradiol combined with leuprolide increases endometriosis-related
      pain.
AB  - OBJECTIVES: To determine if low-dose estrogen replacement can be added to GnRH
      agonist therapy after three months to reduce hypoestrogenic symptoms while
      allowing continued relief of pain in patients with endometriosis. MATERIALS AND
      METHODS: Thirteen women with endometriosis and pain were treated with six months
      of leuprolide acetate in a prospective, randomized double-blind placebo
      controlled study. After three months of therapy, six subjects initiated oral
      estradiol 1 mg daily, and seven received an identical placebo. RESULTS:
      Dysmenorrhea improved in both groups, and dyspareunia significantly improved in
      the GnRH agonist plus placebo group. The mean pain scores of the oral estrogen
      group tended to be higher than the placebo group, and hot flushes tended to be
      less severe with estrogen treatment. However, differences observed between the
      study and placebo groups did not reach statistical significance. CONCLUSION: In a
      prospective, randomized study, low-dose estrogen replacement increases
      endometriosis-related pain during GnRH agonist therapy. The study was terminated
      after the first 13 subjects due to the concerning trend toward recurrent symptoms
      in women who received oral estradiol during GnRH agonist therapy for
      endometriosis-related pain. With the trend toward increasing pain with estrogen
      add-back therapy, a larger study would not seem to be justifiable.

PMID- 10917115
TI  - The importance of intraoperative cholangiography during laparoscopic
      cholecystectomy.
AB  - Laparoscopic cholecystectomy (LC) using an electrosurgery energy source was
      successfully performed in 59 (95%) out of 62 selected patients. The procedures
      were performed by different surgical teams at Trakya University, Medical Fakulty,
      in the department of General Surgery and the Karl-Franzens-University School of
      Medicine, in the department of General Surgery. Cholangiography was routine at
      Karl Franzens University and selective at Trakya University. Laparoscopic
      intraoperative cholangiography (IOC) was performed in 48 (81.3%) patients, and
      open IOC was performed in 3 patients. Two patients had common duct stones; one of
      which was unsuspected preoperatively. These cases underwent endoscopic retrograde
      cholangiopancreatography (ERCP) and endoscopic papillotomy (EP). One patient had
      a choledocal tumor, unsuspected preoperatively. Anatomical anomalies were not
      identified. Cholangiography could not be performed in one case in which there was
      no suspected pathology. ERCP was performed on one patient 30 days after being
      discharged because of acute cholangitis. In this case, residual stones were
      identified in the choledocus. Four patients underwent open cholecystectomy
      because of tumor, unidentified cystic duct or common bile duct pathology that
      could not be visualized on the cholangiogram. Our study suggests that
      cholangiography performed via the cystic duct before any structures are divided
      can prevent the most serious complication of laparoscopic cholecystectomy--common
      duct injury. We recommend that cholangiography be attempted on all patients
      undergoing LC.

PMID- 10917116
TI  - The efficacy of preoperative endoscopic retrograde cholangiopancreatography in
      the detection and clearance of choledocholithiasis.
AB  - BACKGROUND AND OBJECTIVES: Endoscopic retrograde cholangiopancreaticography has
      been reported to have a high success rate in the detection and treatment of
      choledocholithiasis. Although there is growing enthusiasm for laparoscopic common
      bile duct clearance, many patients who present with gallbladder disease and
      suspected choledocholithiasis have endoscopic retrograde cholangiopancreatography
      performed with choledocholithiasis cleared if detected. These patients are then
      referred for laparoscopic cholecystectomy. The purpose of this study is to
      determine the efficacy of preoperative endoscopic retrograde
      cholangiopancreatography in the diagnosis and clearance of bile duct stones at
      our institution. METHODS: A retrospective review was performed of all patients at
      this institution who underwent preoperative endoscopic retrograde
      cholangiopancreatography for suspected choledocholithiasis followed by
      laparoscopic cholecystectomy from January 1997 through July 1998. RESULTS: Common
      bile duct stones were detected endoscopically in 12 of 17 (71%) patients. We
      found serum bilirubin level to be the best predictor of choledocholithiasis. In
      12 of 12 procedures, the endoscopist performed an endoscopic sphincterotomy with
      stone extraction and reported a fully cleared common bile duct. Intraoperative
      cholangiogram performed during subsequent cholecystectomy revealed
      choledocholithiasis in 4 of these 12 patients. Laparoscopic techniques
      successfully cleared the choledocholithiasis in 3 of these patients with open
      techniques necessary in the fourth. CONCLUSIONS: Our data suggests that even
      after presumed successful endoscopic clearance of the bile duct stones, many
      patients (33% in our series) still have choledocholithiasis present at the time
      of cholecystectomy. We recommend intraoperative cholangiography at the time of
      cholecystectomy even after presumed successful endoscopic retrograde
      cholangiopancreatography with further intervention, preferably laparoscopic, to
      clear the choledocholithiasis as deemed necessary.

PMID- 10917117
TI  - Laparoscopic splenectomy in pediatric patients with hematologic diseases.
AB  - OBJECTIVE: The aim of this study was to evaluate our experience with laparoscopic
      splenectomy in pediatric patients with hematologic diseases. METHODS: A
      retrospective chart review was performed to analyze the following: indication for
      splenectomy, pre- and peri-operative management, surgical technique,
      complications, duration of hospitalization, and outcome. RESULTS: Eleven patients
      underwent laparoscopic splenectomy for the following indications: recurrent
      thrombocytopenia (<10,000) in seven with chronic immune thrombocytopenic purpura;
      anemia in two with hereditary spherocytosis; and hypersplenism in one and
      recurrent splenic sequestration in another with homozygous hemoglobin S. The six
      girls and five boys had a median age of 7 years. The median operative time was
      180 minutes, and the median hospitalization was 72 hours. Among the patients with
      immune thrombocytopenic purpura (median platelet count, 153,000), those patients
      (n=3) with platelet counts of <100,000 did not suffer any bleeding complications.
      The patient with hypersplenism and homozygous hemoglobin S required a small
      incision in the left lower quadrant to facilitate removal of a 558-gram spleen.
      This patient also underwent cholecystectomy for cholelithiasis. The operative
      time was 295 minutes, and he was hospitalized for 5 days because of atelectasis.
      CONCLUSIONS: Laparoscopic splenectomy is a safe and effective procedure in
      children with hematological disorders.

PMID- 10917118
TI  - Open versus laparoscopic appendectomy in children: a comparison of complications.
AB  - Although between 4% and 20% of all appendectomies in adults are performed
      laparoscopically, this procedure is rarely done in the pediatric age group
      because of the substantially more difficult technique, the expected risks and
      suspected higher rate of complications. In a prospective study of 500 consecutive
      appendectomies, we tried to assess the actual rate of complications of each
      operative approach. We included 362 conventional and 138 laparoscopic
      appendectomies, the median age of the patients was 10.8 years. The mortality was
      0 in both groups. We observed 89 minor and 11 major complications. All major
      complications (wound infections needing re-operation under general anesthesia,
      intra-abdominal abscesses, ileus due to adhesions and a case of renal
      insufficiency because of glomerulonephritis) occurred in the conventional group
      (n=11, ie, 3% of 362 open appendectomies). Seventy-two minor complications were
      seen in the same group (20%). In the laparoscopic group, there were 17 (13%)
      minor complications and no severe complications. This difference was
      statistically significant. We conclude that in children laparoscopic appendectomy
      does not carry a greater risk of intra- or postoperative complications and can
      therefore safely be established as a standard procedure.

PMID- 10917119
TI  - Laparoscopic operative technique for adrenal tumors.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopy has acquired an unquestionable position in
      surgical practice as a diagnostic and operative tool. Recently, the laparoscopic
      approach has become a valuable option for adrenalectomy. This paper reports, in
      detail, our experience of laparoscopic adrenalectomy performed for adrenal
      tumors. METHODS: We performed 12 laparoscopic adrenalectomies from October 29,
      1997 to October 31, 1998. The technique of laparoscopic adrenalectomy is
      described thoroughly in all relevant details for either left or right-sided
      adrenal lesions. RESULTS: The presented technique of laparoscopic adrenalectomy
      in all 12 cases provided good and relatively simple exposure of the immediate
      operative area. All relevant vascular elements were safely controlled, adrenal
      tumors could be successfully removed, and adequate hemostasis was achieved. No
      intraoperative or postoperative complications were observed. CONCLUSIONS:
      Laparoscopic adrenalectomy is a safe alternative to open surgery and is preferred
      for most patients because of shorter postoperative hospital stay and less
      postoperative discomfort.

PMID- 10917120
TI  - Current considerations in laparoscopic incisional and ventral herniorrhaphy.
AB  - Laparoscopic ventral and incisional herniorrhaphy is gaining popularity among
      both surgeons and patients. The key to the success of this procedure is avoidance
      of complications. In this article, important considerations in the preoperative,
      intraoperative, and postoperative aspects of this procedure are reviewed, with a
      particular focus on the repair of incisional defects. Surgical considerations to
      assist in the prevention of certain pitfalls associated with laparoscopic repair
      of ventral and incisional hernias are described.

PMID- 10917121
TI  - Laparoscopic treatment of ventral abdominal wall hernias: preliminary results in
      100 patients.
AB  - OBJECTIVE: The laparoscopic treatment of eventrations and ventral hernias has
      been little used, although these hernias are well suited to a laparoscopic
      approach. The objective of this study was to investigate the usefulness of a
      laparoscopic approach in the surgical treatment of ventral hernias. METHODS:
      Between January 1994 and July 1998, a series of 100 patients suffering from major
      abdominal wall defects were operated on by means of laparoscopic techniques, with
      a mean postoperative follow-up of 30 months. The mean number of defects was 2.7
      per patient, the wall defect was 93 cm2 on average. There were 10 minor hernias
      (<5 cm), 52 medium-size hernias (5-10 cm), and 38 large hernia (>10 cm). The
      origin of the wall defect was primary in 21 cases and postsurgical in 79. Three
      access ports were used, and the defects were covered with PTFE Dual Mesh
      measuring 19 x 15 cm in 54 cases, 10 x 15 cm in 36 cases, and 12 x 8 cm in 10
      cases. An additional mesh had to be added in 21 cases. In the last 30 cases, PTFE
      Dual Mesh Plus with holes was employed. RESULTS: Average surgery time was 62
      minutes. One procedure was converted to open surgery, and only one patient
      required a second operation in the early postoperative period. Minor
      complications included 2 patients with abdominal wall edema, 10 seromas, and 3
      subcutaneous hematomas. There were no trocar site infections. Two patients
      developed hernia relapse (2%) in the first month after surgery and were
      reoperated with a similar laparoscopic technique. Oral intake and mobilization
      began a few hours after surgery. The mean stay in hospital was 28 hours.
      CONCLUSIONS: Laparoscopic technique makes it possible to avoid large incisions,
      the placement of drains, and produces a lower number of seromas, infections and
      relapses. Laparoscopic access considerably shortens the time spent in the
      hospital.

PMID- 10917122
TI  - A multicentric comparison of transabdominal versus totally extraperitoneal
      laparoscopic hernia repair using PARIETEX meshes.
AB  - The authors report a series of 1972 inguinal hernias treated between 1993 and
      1997 by the insertion of a PARIETEX mesh via either a transabdominal
      preperitoneal (TAPP) (1,290 procedures) or a totally extraperitoneal TEP approach
      (682 procedures). Pain scores were equivalent in both groups, while the hospital
      stay and time to return to normal activity was lower in the TEP group than in the
      TAPP group (p<0.001). In both groups, the average incidence of the total reported
      events (complications) was around 10% with no statistical difference. This ratio
      seemed to compare favorably to previously published reports. Chronic pain was
      extremely rare (0.6% and 0.7% in the TAPP and TEP groups, respectively). Whatever
      the approach was, sepsis was also very rare (1/1,526 laparoscopic procedures).
      These findings illustrate the local tolerance of the mesh. Recurrence rates were
      below 1% with no statistical difference between groups. This retrospective study
      demonstrates the clinically apparent local tolerance of this type of mesh.
      Prospective and long-term clinical results will be necessary to demonstrate that
      the optimized short-term tolerance of PARIETEX mesh will influence the long term
      functional results.

PMID- 10917123
TI  - Laparoscopic cholecystectomy in patients with bilharzial portal hypertension.
AB  - OBJECTIVE: The purpose of this study was to evaluate the results of laparoscopic
      cholecystectomy in patients with bilharzial portal hypertension. METHODS:
      Patients who had gallstones and bilharzia had ultrasonographic assessment of peri
      portal fibrosis, endoscopy, hemagglutination and rectal snip. Operating time,
      blood loss, hospital stay, time of return to work and operative mortality were
      recorded. Follow-up was two weeks, six weeks and six months after discharge.
      RESULTS: Twenty-five out of 450 patients, who had laparoscopic cholecystectomy,
      suffered from bilharzial portal hypertension. Ten patients had grade 1 varices,
      10 had grade 2 varices, and 5 had grade 3 esophageal varices. All patients had
      varying degrees of peri-portal fibrosis as shown by ultrasound. Rectal snip
      showed schistosoma mansoni in 5 patients, and a hemagglutination test was
      positive in all. Two patients had conversion to open cholecystectomy. Mean
      operating time was 1 hour and 15 minutes. Average blood loss was 50 cc. Mean
      hospital stay for 23 patients was 48 hours. Average time of return to work was 2
      weeks in 23 patients and 6 weeks in the 2 patients who had conversion. Twenty-two
      patients benefited from the operation. There was no mortality in this series.
      CONCLUSIONS: Laparoscopic cholecystectomy in patients with bilharzial portal
      hypertension is feasible and has low morbidity.

PMID- 10917124
TI  - Laparoscopic removal of a perforated intrauterine device from the perirectal fat.
AB  - BACKGROUND: The intrauterine device (IUD) was a very common form of birth control
      in the United States. The most serious potential complication of IUD use is
      uterine perforation. Uterine perforation is common among women with "lost" IUDs
      and can cause severe morbidity and mortality and should be carefully managed. The
      recommended treatment is removal of the perforating IUD. This can usually be
      managed laparoscopically unless bowel perforation or other severe sepsis is
      present. METHODS: An intra-abdominal IUD was removed laparoscopically from the
      perirectal fat of a 49-year-old woman who had been diagnosed over 20 years
      earlier with an "expelled" IUD. CONCLUSIONS: It is important that the possibility
      of uterine perforation be considered in anyone who has had a diagnosis of an
      expelled IUD without actual confirmation that the IUD is no longer present in the
      body. In any woman who presents with pelvic pain and a history of a "lost" IUD,
      the surgeon should have a high index of suspicion and obtain radiological
      studies. It may be advisable to question women about possible IUD use when they
      present with pelvic pain of unknown origin.

PMID- 10917125
TI  - Repair of common bile duct injury with the round and falciform ligament after
      clip necrosis: case report.
AB  - Occasionally, as abdominal surgeons, we are confronted with common bile duct
      injury noted during video laparoscopic or open cholecystectomy. Usually this is
      solved by endoscopic retrograde cholangiopancreatography (ERCP) sphincterotomy
      and stent, or enteric bypass, suture repair and tube drainage. However, after
      such procedures, there is a significant number of patients with postoperative
      stenosis. Another alternative to repair common bile duct injury and correct
      postoperative stenosis is using the round and falciform ligament as
      circumferencial patch. Due to their closeness to the common bile duct and their
      adequate blood supply, they make a perfect autologous biological graft.

PMID- 10917126
TI  - Extrahepatic biliary obstruction due to post-laparoscopic cholecystectomy biloma.
AB  - BACKGROUND: Jaundice presenting after cholecystectomy may be the initial
      manifestation of a serious surgical misadventure and requires rigorous diagnostic
      pursuit and therapeutic intervention. Biloma is a well recognized
      postcholecystectomy complication that often accompanies biliary ductal injury.
      CASE REPORT: A 23-year-old female underwent laparoscopic cholecystectomy for
      symptomatic gallstones and three weeks postoperatively developed painless
      jaundice. Radiographic and endoscopic studies revealed a subhepatic biloma
      causing extrinsic compression and obstruction of the common hepatic duct.
      RESULTS: Percutaneous catheter drainage of the biloma combined with endoscopic
      sphincterotomy successfully relieved the extrahepatic biliary obstruction and
      resolved the intrahepatic ductal leak responsible for the biloma. CONCLUSION:
      Although heretofore undescribed, postcholecystectomy jaundice due to extrahepatic
      bile duct obstruction caused by biloma may occur and can be successfully treated
      by means of standard radiologic and endoscopic interventions.

PMID- 10917127
TI  - Laparoscopic pyloroplasty in idiopathic hypertrophic pyloric stenosis in an
      adult.
AB  - BACKGROUND AND OBJECTIVES: Idiopathic hypertrophic pyloric stenosis, in adults,
      is a rare disease. Partial gastrectomy, gastroenterostomy, pyloromyotomy,
      pyloroplasty and endoscopic dilatation have all been recommended with variable
      results. A 54-year-old white female is presented with the onset of symptoms of
      idiopathic hypertrophic pyloric stenosis one year prior to operation. Two
      endoscopic pyloric sphincter balloon dilatations provided only temporary relief.
      METHOD: A laparoscopic pyloroplasty was performed. RESULT: The patient tolerated
      a solid diet on postoperative day three. The patient was symptom-free at a 13
      month follow-up. CONCLUSIONS: Idiopathic hypertrophic pyloric stenosis in adults
      can be treated with laparoscopic pyloroplasty, offering a minimally invasive
      alternative to open repair.

PMID- 10917128
TI  - Hernia of foramen of Morgagni in adult: case report of laparoscopic repair.
AB  - The videolaparoscopic repair of a diaphragmatic hernia of Morgagni by external
      knot tying technique is described. A 69-year-old woman with subocclusive symptoms
      by intrathoracic migration of abdominal viscera had an immediate and complete
      postoperative recovery. The hernial sac was not excised. A four-year follow-up
      shows no hernia recurrence. This case indicated that the laparoscopic approach
      can be considered a suitable and safe procedure for treatment of Morgagni's
      hernia.

PMID- 10917129
TI  - Laparoscopy in the management of children with chronic recurrent abdominal pain.

PMID- 10917130
TI  - Deregulation of the cell cycle in cancer.
AB  - Mitogenic and growth-inhibitory signals influence cell-cycle progression through
      their action on a family of cyclin-dependent kinases (cdks). The activity of cdk
      complexes is regulated in part by the association of a cyclin partner that acts
      as a positive effector and by two families of cdk inhibitors, the kinase
      inhibitor proteins (KIP) and the inhibitors of cdk4 (INK4), which act as negative
      effectors. In human malignancies, increased expression of cyclins is frequently
      observed. Cyclin D1 and E are frequently overexpressed in breast cancers, and
      cyclin E overexpression has been correlated with a poor prognostic outcome. The
      abrogated expression or the acquisition of mutations that render cdk inhibitors
      functionally inactive have similarly been found in human malignancies. The p16
      gene is frequently deleted or mutated in cancers. Although normal epithelial
      cells express high levels of p27 protein, reduced levels of p27 have been
      observed in several human cancers, and this has been consistently correlated with
      a poor prognostic outcome. In this review, we will provide a brief overview of
      the cell cycle regulators and then discuss their deregulation in cancers.

PMID- 10917131
TI  - DNA content of nasopharyngeal carcinoma: an independent prognostic indicator.
AB  - The purpose of this study was to examine whether tumor DNA content correlated
      with prognosis in nasopharyngeal carcinoma (NPC). DNA flow-cytometric analysis in
      fresh specimens of nasopharyngeal biopsy from 123 patients with clinical
      suspicion of NPC was collected initially. Histopathologic study and successful
      flow-cytometric analysis had 28 lymphoid hyperplasias and 87 NPCs. Seventeen NPC
      patients were treated elsewhere and were excluded. A total of 98 patients,
      including 28 lymphoid hyperplasias and 70 NPCs, formed the materials of this
      study. There were 34 (49%) diploid and 36 (51%) aneuploid in NPC patients. No
      lymphoid hyperplasias were aneuploid. The mean of S-phase fraction was higher in
      NPC than in lymphoid hyperplasia (P < .001), indicating higher cellular activity
      in NPC. DNA content failed to associate with age, gender, pathology, distant
      metastasis, and stage, indicating that DNA content was an independent prognostic
      indicator and possibly a clinical parameter. The log-rank test of overall
      survival curves was significant for stage (P = .002) and DNA ploidy (P = .042);
      it was almost significant for S-phase fraction (P = .057). Because the follow-up
      duration was not long enough, univariate and multivariate analysis were not
      significant for stage, ploidy, and S-phase fraction, except for distant
      metastasis. It is also most likely colinearity of clinical stage and distant
      metastasis that explained why clinical stage could not show significance in
      prognosis. Interestingly, the DNA content appeared to be a potential prognostic
      parameter in overall survival, although it was not statistically significant (P =
      .052). Our data suggested that NPC patients with aneuploid DNA and high S-phase
      fraction tend to have poor prognosis and should be treated more aggressively,
      even in the early stage of the disease.

PMID- 10917132
TI  - Dietary calcium and growth modulation of human colon cancer cells: role of the
      extracellular calcium-sensing receptor.
AB  - Using the human colon adenocarcinoma-derived cell line Caco-2, we investigated
      the possible role of the Ca2+-sensing receptor (CaR) in mediating effects of
      extracellular Ca2+ on cellular proliferation. Caco-2 cells respond to low ambient
      [Ca2+]o by activation of the protein kinase C-signaling pathway, leading to
      upregulation of c-myc mRNA expression and thereby, finally, to alleviation from
      the G1/S phase control of the cell cycle. This proliferative response can be
      reverted by activation of the CaR either through raising [Ca2+]o or,
      respectively, by using the CaR agonist Gd3+ as a substitute for Ca2+. The
      inhibitory effect of [Ca2+]o on cell replication exhibits saturation kinetics
      (IC50 = 0.045 mM), indicating the existence of a highly sensitive CaR operating
      at low ambient [Ca2+]o. Specific immunostaining revealed the presence of CaR
      positive cells in the crypt epithelium of normal human colonic mucosa as well as
      in glandular (i.e., differentiated structures) of carcinomatous lesions. This
      could provide a rationale for use of calcium supplements for intervention in
      early phases of colon tumorigenesis.

PMID- 10917133
TI  - Surveillance improves survival of colorectal cancer in patients with hereditary
      nonpolyposis colorectal cancer.
AB  - Some patients with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome
      develop carcinoma despite surveillance. The aim of this study was to determine
      whether survival was greater in colorectal cancer (CRC) cases detected by
      surveillance than in patients who had disease diagnosed on the basis of symptoms.
      All 150 CRC cases detected in 57 HNPCC families over the last 15 years were
      divided into two groups depending on whether they had been included in the
      surveillance program (n = 35) or not (n = 115). The stage distribution of the
      tumors in the group that underwent surveillance (Dukes' A, 50%; B, 35%; C, 15%;
      D, 0%) was significantly more favorable (P < .001) than in the group without
      surveillance (Dukes' A, 17%; B, 50%; C, 16%; D, 17%). CRC-specific 10-year
      survival was 93% in the surveillance group, significantly better than the 68% in
      the nonsurveillance group (P < .02). The overall survival did not differ
      significantly between the two groups despite a tendency in favor of the
      surveillance group. Colonoscopic surveillance enables early detection of CRC in
      HNPCC and reduces CRC mortality.

PMID- 10917134
TI  - Alpha-L-fucosidase enzyme in the prediction of colorectal cancer patients at high
      risk of tumor recurrence.
AB  - The aim of this study was to examine the prognostic value of the alpha-L
      fucosidase enzyme to determine whether it can help in the early recognition of
      colorectal cancer cases at high risk of tumor recurrence. One hundred and twenty
      three colorectal carcinoma patients treated by curative surgery were studied. The
      alpha-L-fucosidase activity was assayed in the tumor and in normal mucosa from
      each patient using a fluorometric method. Seven other clinical and pathologic
      features were also studied. To evaluate the impact of each variable over the
      disease-free interval, a postoperative 30-month follow-up of patients was
      performed, and a statistical survival analysis was carried out. The recurrence
      appearance was higher when the relative decrease of alpha-L-fucosidase activity
      was more than 52% (log-rank test, P = .0261). The results of this work indicate
      that alpha-L-fucosidase activity appears to be a good independent prognostic
      factor of tumoral recurrence in colorectal carcinoma.

PMID- 10917136
TI  - A measure of skin familiarity and its role in the early detection of skin cancer.
AB  - Skin self-examination (SSE) is promoted widely so that individuals will become
      familiar with their skin and be better able to identify suspicious changes
      earlier. However, individuals can also become familiar with their skin other than
      through purposeful SSE. In this article, we develop a measure of skin familiarity
      based on the density of spots on 14 different areas of the body. A factor
      analysis of the 14 body-area scores revealed that they could be grouped into four
      broad body regions (shoulders and back, front of legs, back of legs, and feet).
      Each total body score and body-region score has high internal consistency
      (Cronbach's alpha coefficients ranging from 0.79 to 0.93). Moreover, the scores
      correlate as expected with skin self-examination behaviors and other personal
      characteristics, indicating high construct validity. We consider the advantages
      that skin familiarity measures offer over the exclusive use of SSE measures in
      the assessment of early detection activities and discuss the direction of future
      research in this area.

PMID- 10917135
TI  - Evaluation of circulating activin-A as a serum marker of hepatocellular
      carcinoma.
AB  - Because in experimental hepatocarcinogenesis apoptosis increases from normal to
      preneoplastic to carcinoma tissue, proapoptotic factors, such as activin-A, may
      represent useful markers for hepatocellular carcinoma (HCC). In this study, serum
      activin-A was measured in 99 cirrhotic patients, of whom 55 had HCC. Activin-A
      concentrations were higher in HCC patients (median, 2.33 ng/ml; range, 0.41-8.12)
      than in patients with nonmalignant cirrhosis (1.28 ng/ml; range, 0.35-6.25) (P <
      .05). All 12 patients with activin-A greater than 3 ng/ml and serum alpha
      fetoprotein greater than 30 ng/ml had HCC, in comparison to 32 of 41 patients who
      had only one and to 11 of 46 patients who had both markers below these cutoffs (P
      < .0001). No correlation was found between activin-A and alpha-fetoprotein in the
      two groups, whereas in patients with HCC, activin-A was strictly correlated with
      serum aspartate aminotransferase (P < .001). Activin-A mRNA for inhibin betaA
      subunit was expressed both in tumor and nontumor liver tissues in a case of HCC
      superimposed on cirrhosis and was not expressed in a case of HCC without
      cirrhosis. In conclusion, cirrhotic patients with HCC have high serum activin-A,
      to the production of which both the cirrhotic liver and the liver tumor are
      likely to contribute.

PMID- 10917137
TI  - Human meningiomas: immunohistochemical localization of progesterone receptor and
      heat shock protein 27 and absence of estrogen receptor and PS2.
AB  - Formalin-fixed, paraffin-embedded tumor specimens from 64 human meningiomas of
      various histologic types were immunostained using a streptavidin-peroxidase
      method and monoclonal antibodies for estrogen receptors (ER) and progesterone
      receptors (PgR) and hormone-induced proteins PS2 and heat shock protein 27
      (Hsp27). The immunohistochemical analysis was scored in a semiquantitative
      fashion incorporating both the intensity and distribution of specific staining
      (score). Strong PgR nuclear immunoreactivity (mean score, 54.2) was observed in
      51 of 64 meningiomas (80%). Meningiomas with atypical features were negative for
      PgR. Low Hsp27 cytoplasmic immunoreactivity (mean score, 9.8)--irrespective of
      histologic type--was observed in 26 of 64 meningiomas (40%). Whor1 formations in
      transitional meningiomas were Hsp27-positive. Hsp27 immunoreactivity was observed
      in tumor blood vessels. All neoplasms were negative for ER and PS2. Normal
      arachnoid tissue was positive for PgR and negative for ER, PS2, and Hsp27.
      Compared with previously reported data on gliomas, the results of this study
      indicate that meningiomas show a clear out difference concerning the expression
      of PgR and Hsp27.

PMID- 10917139
TI  - Effects of oral administration of Pfaffia paniculata (Brazilian ginseng) on
      incidence of spontaneous leukemia in AKR/J mice.
AB  - Pfaffia paniculata (Brazilian ginseng) administered subcutaneously and
      intraperitoneally inhibits growth of allogeneic cancer cells in mice. The goal of
      this study was to determine whether oral administration of P. paniculata inhibits
      development of spontaneous leukemia. Four-week-old female AKR/J mice were given
      oral doses of powdered roots from P. paniculata three times weekly for 8 weeks;
      controls received phosphate-buffered saline. Enlargement of thymic lymphoma in
      the mice treated with P. paniculata was significantly suppressed, as compared
      with controls (128 +/- 67.3 mg versus 219.9 +/- 84.2 mg, respectively; P < .01);
      proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the
      thymus was markedly inhibited after the first oral treatment as compared with
      untreated controls (final age, 28 weeks; P < .05). In normal 3-week-old female
      AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection
      into the thymus of cell-free extract of thymus from the experimental female 28
      week-old AKR/J mice that received the oral P. paniculata preparation. These
      results suggest that the agent's suppressive effects on spontaneously occurring
      leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on
      enhancement of nonspecific immune or cellular immune systems (or both) by the P.
      paniculata preparation.

PMID- 10917138
TI  - Fluorescence in situ hybridization evaluation of minimal residual disease on stem
      cell harvests.
AB  - The usefulness of fluorescence in situ hybridization (FISH) analysis to detect
      minimal residual disease (MRD) in autologous bone marrow and peripheral blood
      stem-cell harvests has been tested in three patients with hematologic
      malignancies. Conventional cytogenetics and FISH were used to characterize the
      leukemic clones identifying the specific chromosomal abnormalities (monosomy 7 in
      a myelodysplastic patient and trisomy 8 in two acute myeloid leukemic patients).
      Such analysis was useful to monitor the MRD persistent after treating these
      patients with intensive chemotherapy. The myelodysplastic patient underwent eight
      peripheral blood-stem cell harvests in which FISH detected the persistence of
      monosomy 7 cells, precluding their use for autologous transplantation. This
      patient relapsed and died. In two acute myeloid leukemia patients who underwent
      an autologous marrow harvest, FISH did not show a significant proportion of
      trisomy 8 cells. Nevertheless, autologous transplantation was not performed,
      owing to an insufficient CD34 cell content in the harvests. One of these patients
      relapsed with the reappearance of trisomy 8 and died. The other patient, on the
      contrary, is alive in complete remission 3 years after the bone marrow harvest.
      The usefulness and applicability of MRD quantification in stem-cell harvests is
      discussed on the basis of the sensitivity of the methodology applied.

PMID- 10917140
TI  - Cervical intraepithelial neoplasia in human immunodeficiency virus-positive
      patients.
AB  - Cervical intraepithelial neoplasia (CIN) is common in patients positive for human
      immunodeficiency virus (HIV). The questions are whether the management of CIN in
      these patients should be different from that of HIV-negative women, whether there
      are any prognostic factors to indicate the course of CIN, and whether the latter
      is influenced by antiretroviral therapy. A total of 267 HIV-seropositive women
      were counseled and examined in our colposcopic clinic. Of that number, 53
      patients died during the observation period; 74% of these patients were
      immunosuppressed (CD4 count < 200 cells/mm3), and 45% were given diagnoses of
      CIN. The incidence of CIN was significantly higher in patients with CD4 less than
      200 cells/mm3. Neither the route of HIV infection nor the HPV status nor smoking
      habits correlated with CIN. CIN relapse was histologically confirmed in 28% of
      patients who underwent complete surgical removal. Immune status plays an
      important role in HIV-positive women not only with respect to survival but with
      respect to CIN.

PMID- 10917141
TI  - Knowledge of and attitudes about cancer among American Samoans.
AB  - The objective of this study was to determine cancer-related knowledge and
      attitudes among American Samoans, a population seldom studied by cancer
      researchers. Such information is necessary to develop culturally sensitive cancer
      control interventions. Specially trained personnel conducted face-to-face
      interviews with randomly selected respondents in the US Territory of American
      Samoa; Oahu, HI; and Los Angeles, CA, using a survey based on the National Health
      Interview Survey Cancer Control Supplement and focus group findings. The survey
      included questions concerning knowledge of risk factors for cancers (breast,
      cervical, colon, lung, stomach, and prostate), family resources (health insurance
      coverage, employment status, and family income), and demographic characteristics.
      Participants could complete the survey in English or Samoan. Analysis of data
      included the chi-squared test and logistic regression analysis. Participants
      included 1,834 noninstitutionalized English- or Samoan-speaking women and men
      (609 from American Samoa, 610 from Hawaii, and 615 from Los Angeles). The
      majority of residents had some positive attitudes about cancer prevention and
      treatment but often also had misconceptions about risk factors for cancer.
      Logistic regression analysis revealed that site of residence was an important
      predictor of attitudes. For example, being residents of American Samoa or Hawaii
      predicted that the respondents would rather not know that they had cancer (odds
      ratio [OR], 1.5, 2.1, respectively); that cancer can be caused by aitu, or
      spirits (OR, 1.9, 2.1, respectively); that cancer is a punishment from God (OR,
      2.0, 2.2, respectively); and that cancer can be cured by fofo, or traditional
      Samoan healers (OR, 2.0, 3. 1, respectively). This study documented cancer
      related knowledge and attitudes among American Samoans and set the stage for
      culturally sensitive interventions aimed at improving cancer control in this
      population. It also identified many issues that should be addressed in such
      interventions.

PMID- 10917142
TI  - Studying cognitive systems in context: preface to the special section.

PMID- 10917143
TI  - Contending with complexity: developing and using a scaled world in applied
      cognitive research.
AB  - Scaled worlds preserve certain functional relationships of a complex task
      environment while paring away others. The functional relationships preserved are
      defined by the questions of interest to the researcher. Different scaled worlds
      of the same task may preserve and pare away different functional relationships.
      In this paper we use the example of Ned to discuss the use of scaled worlds in
      applied cognitive research. Ned is based on a detailed cognitive task analysis of
      submarine approach officers as they attempt to localize an enemy submarine hiding
      in deep water. For Ned we attempted to preserve the functional relationships
      inherent in the approach officer's information environment while paring away
      other aspects of his task environment. Scaled worlds attempt to maintain the
      realism inherent in the preserved functional relationship while being tractable
      for the researcher and engaging to the participant.

PMID- 10917144
TI  - The utility of event-based knowledge elicitation.
AB  - The purpose of this investigation was to describe and evaluate an event-based
      knowledge elicitation technique. With this approach experts are provided with
      deliberate and controlled job situations, allowing investigation of specific task
      aspects and the comparison of expert responses. For this effort a videotape was
      developed showing an instructor pilot and student conducting a training mission.
      Various job situations were depicted in the video to gather information pertinent
      to understanding team situational awareness. The videotape was shown to 10
      instructors and 10 student aviators in the community, and responses to the
      videotape were collected using a questionnaire at predetermined stop points.
      Consistent with expectations, the results showed that more experienced
      respondents (i.e., instructors) identified a richer database of cues and were
      more likely than students to identify strategies for responding to the situations
      depicted, providing some empirical evidence for the validity of the event-based
      technique. This method may serve as a useful knowledge elicitation technique,
      especially in the later stages of a job analysis when focused information is
      sought.

PMID- 10917146
TI  - Factors influencing analysis of complex cognitive tasks: a framework and example
      from industrial process control.
AB  - We propose that considering four categories of task factors can facilitate
      knowledge elicitation efforts in the analysis of complex cognitive tasks:
      materials, strategies, knowledge characteristics, and goals. A study was
      conducted to examine the effects of altering aspects of two of these task
      categories on problem-solving behavior across skill levels: materials and goals.
      Two versions of an applied engineering problem were presented to expert,
      intermediate, and novice participants. Participants were to minimize the cost of
      running a steam generation facility by adjusting steam generation levels and
      flows. One version was cast in the form of a dynamic, computer-based simulation
      that provided immediate feedback on flows, costs, and constraint violations, thus
      incorporating key variable dynamics of the problem context. The other version was
      cast as a static computer-based model, with no dynamic components, cost feedback,
      or constraint checking. Experts performed better than the other groups across
      material conditions, and, when required, the presentation of the goal assisted
      the experts more than the other groups. The static group generated richer
      protocols than the dynamic group, but the dynamic group solved the problem in
      significantly less time. Little effect of feedback was found for intermediates,
      and none for novices. We conclude that demonstrating differences in performance
      in this task requires different materials than explicating underlying knowledge
      that leads to performance. We also conclude that substantial knowledge is
      required to exploit the information yielded by the dynamic form of the task or
      the explicit solution goal. This simple model can help to identify the contextual
      factors that influence elicitation and specification of knowledge, which is
      essential in the engineering of joint cognitive systems.

PMID- 10917145
TI  - There is more to monitoring a nuclear power plant than meets the eye.
AB  - A fundamental challenge in studying cognitive systems in context is how to move
      from the specific work setting studied to a more general understanding of
      distributed cognitive work and how to support it. We present a series of
      cognitive field studies that illustrate one response to this challenge. Our focus
      was on how nuclear power plant (NPP) operators monitor plant state during normal
      operating conditions. We studied operators at two NPPs with different control
      room interfaces. We identified strong consistencies with respect to factors that
      made monitoring difficult and the strategies that operators have developed to
      facilitate monitoring. We found that what makes monitoring difficult is not the
      need to identify subtle abnormal indications against a quiescent background, but
      rather the need to identify and pursue relevant findings against a noisy
      background. Operators devised proactive strategies to make important information
      more salient or reduce meaningless change, create new information, and off-load
      some cognitive processing onto the interface. These findings emphasize the active
      problem-solving nature of monitoring, and highlight the use of strategies for
      knowledge-driven monitoring and the proactive adaptation of the interface to
      support monitoring. Potential applications of this research include control room
      design for process control and alarm systems and user interfaces for complex
      systems.

PMID- 10917147
TI  - Cognitive task analysis and innovation of training: the case of structured
      troubleshooting.
AB  - Troubleshooting is often a time-consuming and difficult activity. The question of
      how the training of novice technicians can be improved was the starting point of
      the research described in this article. A cognitive task analysis was carried out
      consisting of two preliminary observational studies on troubleshooting in
      naturalistic settings, combined with an interpretation of the data obtained in
      the context of the existing literature. On the basis of this cognitive task
      analysis, a new method for the training of troubleshooting was developed
      (structured troubleshooting), which combines a domain-independent strategy for
      troubleshooting with a context-dependent, multiple-level, functional
      decomposition of systems. This method has been systematically evaluated for its
      use in training. The results show that technicians trained in structured
      troubleshooting solve twice as many malfunctions, in less time, than those
      trained in the traditional way. Moreover, structured troubleshooting can be
      taught in less time than can traditional troubleshooting. Finally, technicians
      learn to troubleshoot in an explicit and uniform way. These advantages of
      structured troubleshooting ultimately lead to a reduction in training and
      troubleshooting costs.

PMID- 10917148
TI  - A framework for epistemological analysis in empirical (laboratory and field)
      studies.
AB  - In their search for generalizable behavioral patterns and design principles,
      cognitive field researchers should reflect on the epistemological limitations of
      empirical studies. In this paper we describe a framework for epistemological
      analysis that can help serve this purpose and discuss its application to two
      prototypical cases of cognitive engineering research: laboratory experiments and
      field studies. The framework examines two, often implicit, processes in empirical
      research: the abstraction from empirical data and the substantiation of
      theoretical constructs and principles. By explicitly considering these two
      processes in several systematic steps, we can gain appreciation for the
      epistemological contribution of empirical studies to cognitive engineering
      research. The framework and its application also provide guidance to such
      important issues as generalizability of results and external validity. Possible
      applications of this research include providing guidance to researchers and
      practitioners in evaluating design principles or conducting field studies.

PMID- 10917149
TI  - Warning research: an integrative perspective.
AB  - We developed an integrative perspective on the empirical evidence supporting the
      influence of particular variables on the warning process based on a broad review
      of the warning literature. The warning process is described in terms of the
      following four components: notice, encode, comprehend, and comply. Relevant
      variables are classified as person variables (characteristics of the individual
      interacting with the warning) and warning variables (characteristics of the
      warning itself or the context in which the warning appears). This integrative
      perspective yields general principles about the variables that influence the
      warning process and serves as a resource for warning developers and as a guide to
      facilitate effective analysis of warnings. We also identify aspects of the
      warning process that are not well understood, directions for effective methods of
      intervention, and a research agenda for future efforts. Actual or potential
      applications of this research include improving the design of warnings.

PMID- 10917150
TI  - Visual display height.
AB  - We examined the influence of backrest inclination and vergence demand on the
      posture and gaze angle that workers adopt to view visual targets placed in
      different vertical locations. In the study, 12 participants viewed a small video
      monitor placed in 7 locations around a 0.65-m radius arc (from 65 degrees below
      to 30 degrees above horizontal eye height). Trunk posture was manipulated by
      changing the backrest inclination of an adjustable chair. Vergence demand was
      manipulated by using ophthalmic lenses and prisms to mimic the visual
      consequences of varying target distance. Changes in vertical target location
      caused large changes in atlanto-occipital posture and gaze angle. Cervical
      posture was altered to a lesser extent by changes in vertical target location.
      Participants compensated for changes in backrest inclination by changing cervical
      posture, though they did not significantly alter atlanto-occipital posture and
      gaze angle. The posture adopted to view any target represents a compromise
      between visual and musculoskeletal demands. These results provide support for the
      argument that the optimal location of visual targets is at least 15 degrees below
      horizontal eye level. Actual or potential applications of this work include the
      layout of computer workstations and the viewing of displays from a seated
      posture.

PMID- 10917151
TI  - Measuring team knowledge.
AB  - Multioperator tasks often require complex cognitive processing at the team level.
      Many team cognitive processes, such as situation assessment and coordination, are
      thought to rely on team knowledge. Team knowledge is multifaceted and comprises
      relatively generic knowledge in the form of team mental models and more specific
      team situation models. In this methodological review paper, we review recent
      efforts to measure team knowledge in the context of mapping specific methods onto
      features of targeted team knowledge. Team knowledge features include type,
      homogeneity versus heterogeneity, and rate of knowledge change. Measurement
      features include knowledge elicitation method, team metric, and aggregation
      method. When available, we highlight analytical conclusions or empirical data
      that support a connection between team knowledge and measurement method. In
      addition, we present empirical results concerning the relation between team
      knowledge and performance for each measurement method and identify research and
      methodological needs. Addressing issues surrounding the measurement of team
      knowledge is a prerequisite to understanding team cognition and its relation to
      team performance and to designing training programs or devices to facilitate team
      cognition.

PMID- 10917152
TI  - Site-specific invasion of the basal ganglia by Nocardia asteroides GUH-2.
AB  - Nocardia asteroides GUH-2 (GUH-2) invades the nigrostriatal region of the brain
      in mice [15]. Selective dopaminergic neuronal dropout in the substantia nigra
      results in parkinsonian changes characterized by movement disorders responsive to
      L-dopa [15]. This is the only reported example of an experimental bacterial model
      for parkinsonism. Following i.v. inoculation of GUH-2 into the non-human primate
      Macaca fasicularius, the nocardiae preferentially invaded and grew within the
      basal ganglia (substantia nigra, caudate, putamen, and globus pallidus) often
      without inducing apparent inflammation. Reduced, limited growth of nocardiae
      occurred in the white matter of the cerebral cortex, medulla, and hippocampus,
      whereas neither significant adherence to nor growth within the meninges was
      observed. Twenty-four hours after injection, nocardial cells were found within
      capillary endothelial cells, the basal lamina, neurons, astroglia and in axonal
      extensions. The bacteria, in endothelial cells, were surrounded by a unit
      membrane, but in the basal lamina they appeared to be free and not membrane
      bound. After the organisms passed into the brain parenchyma, the nocardiae once
      again became surrounded by membrane, often being encapsulated by numerous layers
      with the innermost layer tightly adherence to the bacterial surface. There was a
      propensity for nocardial growth within and along myelinated axons, either with or
      without disruption to the surrounding myelin sheath. There was electron
      microscopic evidence that the nocardiae induced a neurodegenerative response
      especially in the substantia nigra region. Thus, the early interactions of GUH-2
      within the primate brain appeared to be similar to those reported in the mouse.

PMID- 10917153
TI  - Culture independent and rapid identification of bacterial pathogens in
      necrotising fasciitis and streptococcal toxic shock syndrome by fluorescence in
      situ hybridisation.
AB  - Fluorescence in situ hybridisation (FISH) targeted to ribosomal RNA is well
      established for studies in environmental microbiology. Initial applications of
      this technique in the field of medical microbiology showed that FISH is also a
      suitable means for the rapid, reliable and cultivation-independent identification
      of bacterial pathogens. In particular, for infectious diseases that follow a
      fulminant live-threatening course, such as sepsis or necrotising fasciitis (NF),
      a fast and reliable detection technique is of great importance. This study
      describes the development of an rRNA-targeted oligonucleotide set covering more
      than 95% of the pathogens associated with NF. These probes were tested with a
      broad collection of target and non-target organisms and found to be highly
      specific. Subsequently, the FISH approach was applied for the direct detection of
      bacterial pathogens in clinical samples. Two cases of NF and one case of
      streptococcal toxic shock syndrome (STSS) were analysed. FISH correctly
      identified almost all pathogens present in the samples examined within 2-3 h.
      However, Proteus mirabilis, which was identified in one sample by conventional
      methods was detected as a rod-shaped bacteria but could not be identified by
      FISH, since no specific probe was available for this particular organism. In
      contrast, identification of pathogens in these samples by conventional laboratory
      methods took 48-72 h. Furthermore, in one patient with pre-sampling antimicrobial
      therapy bacteria could not be grown from any of the samples. FISH unequivocally
      revealed the presence of Streptococcus pyogenes in affected tissue samples from
      this patient. In an experimental setting we demonstrated that FISH readily
      identifies S. pyogenes cells rendered non-cultivable by antibiotic treatment.

PMID- 10917154
TI  - Binding of human lipoproteins (low, very low, high density lipoproteins) to
      recombinant envelope proteins of hepatitis C virus.
AB  - Heterogeneities in the density of hepatitis C virus (HCV)-RNA-carrying material
      from human sera (1.03-1.20 g/ml) are partially due to the binding of lipoproteins
      [low density (LDL), very low density (VLDL), high density (HDL) lipoproteins] and
      immunoglobulins. In this study we demonstrate the binding of recombinant HCV
      envelope protein (El/E2) to human LDL, VLDL and HDL on a molecular basis. The
      binding of lipoproteins was restricted to the middle part of the El gene product
      (amino acids 222-336) and the C-terminal part of the E2 protein (amino acids 523
      809). Lipoproteins did not bind to recombinant HCV core protein.

PMID- 10917155
TI  - Incomplete replication of human parainfluenza virus type 4 in LLC-MK2 cells and
      in L929 cells.
AB  - Human parainfluenza virus type 4A (hPIV-4A) and type 4B (hPIV-4B) were tested for
      their ability to replicate in the monkey kidney LLC-MK2 cell line (MK2 cells) and
      the murine L929 cell line (L929 cells). These cells are normally non-permissive
      for replication of hPIV-4; however, treatment with acetylated trypsin led to
      virus replication in MK2 cells, but was less effective for L929 cells.
      Endogenously produced interferon (IFN) played no role in virus replication in
      L929 cells. Synthesis of virus-specific polypeptides was suppressed in L929
      cells. Whereas NP-mRNA and HN-mRNA were detected in MK2 cells, no HN-mRNA was
      detected in L929 cells. These results indicate that hPIV-4 can infect both MK2
      cells and L929 cells. In MK2 cells, when protease exists in the extracellular
      medium, hPIV-4 exhibits multistep growth. In L929 cells, however, the cause of
      incomplete replication might be lack of other unknown factors.

PMID- 10917156
TI  - Infection of dendritic cells by enterobacteriaceae.
AB  - Dendritic cells (DC) are potent antigen-presenting cells that play a crucial role
      in initiation and modulation of specific immune responses. Various pathogens like
      viruses or bacteria are able to persist inside DC. In this study we investigated
      the ability of the Gram-negative bacteria Salmonella typhimurium and Escherichia
      coli to infect DC. DC isolated from peripheral blood of healthy donors were
      infected with wild-type S. typhimurium and a nonpathogenic E. coli stool isolate.
      Association of bacteria with DC was assessed by labeling of the bacteria with
      green fluorescent protein. Both Gram-negative bacteria were associated with DC as
      evidenced by microscopy and flow cytometry. The intracellular location could be
      confirmed by lysis of DC and subsequent determination of colony-forming units on
      agar plates, which showed a rapid decline in viable Gram-negative bacteria 6 h
      after infection, being by far more pronounced for E. coli than for S.
      typhimurium. Testing the stimulation of T cells by infected versus uninfected but
      otherwise identically treated human immature DC in a mitogen-dependent T cell
      proliferation assay, we found that S. typhimurium. but not E. coli exhibited a
      suppressive effect on T cell stimulation, being most significant on days 3-5
      after infection. Thus, suppression of dendritic cell function was associated with
      an enteropathogenic bacterium, S. typhimurium, which can cause severe forms of
      enteritis. The bacteria with normally mild or no gastric symptoms, E. coli, had
      no influence on stimulation of T cells by DC.

PMID- 10917157
TI  - Monitoring of cell-free viral DNA in primary Epstein-Barr virus infection.
AB  - Primary Epstein-Barr virus (EBV) infection in childhood is usually asymptomatic,
      but sometimes causes infectious mononucleosis (IM). Very occasionally, IM
      develops into a life-threatening EBV-associated hemophagocytic syndrome (EBV
      AHS). We studied the importance and usefulness of measuring cell-free viral DNA
      in the serum of patients with these primary EBV infections. Using real-time
      quantitative polymerase chain reaction, cell-free EBV-DNA was quantified in the
      serum of nine children with IM and three with EBV-AHS. In the acute phase of IM,
      an average of 10(2.4) copies/ml of EBV-DNA was detected in 95% of sera. The EBV
      load gradually decreased and disappeared within 1 month. Patients with EBV-AHS
      had an extremely high viral load in their sera (10(5.5)-10(7.4) copies/ ml). The
      viral load persisted longer in these patients, although it decreased in parallel
      with the improvement of symptoms. These results indicate that cell-free EBV-DNA
      was frequently detected in patients with primary EBV infection and could,
      therefore, be used as a marker for EBV infection. Measuring the cell-free EBV-DNA
      is useful for monitoring the primary EBV infection, especially in EBV-AHS.

PMID- 10917158
TI  - There is no disease-specific role for streptococci-responsive synovial T
      lymphocytes in the pathogenesis of psoriatic arthritis.
AB  - The initiation or exacerbation of psoriasis vulgaris is associated with
      infections by group A streptococci. T lymphocytes specific for streptococcal
      antigens or expressing a restricted, for streptococcal superantigens typical T
      cell receptor Vbeta chain repertoire have been described in psoriatic skin
      lesions. The aim of our study was, therefore, to clarify whether streptococci
      reactive T lymphocytes played a role in the pathogenesis of psoriatic arthritis
      (PsA), and by which antigens they might be stimulated. Synovial membrane
      mononuclear cells from patients with PsA and other arthropathies, separated by
      collagenase digestion, were expanded in interleukin-2-supplemented medium and
      subsequently cloned in a representative cloning procedure. The T cell lines and
      about 30% of the T cell clones proliferated in response to preparations of group
      A streptococci but not to other bacteria as tested by [3H]thymidine incorporation
      assays. Interestingly, they did not proliferate in response to exotoxin-negative
      streptococci, but did so in response to the streptococcal pyrogenic exotoxins A
      and C, which are known to be superantigens. Accordingly, no HLA-DR restriction
      was seen for the proliferative response. The remaining 70% of the established T
      cell clones did not react to an antigen of group A streptococci. Our results show
      that in patients with PsA, osteoarthritis or rheumatoid arthritis a significant
      number of synovial T lymphocytes were responsive to streptococcal superantigens,
      but not to conventional streptococcal antigens. A disease-specific role of
      streptococci-reactive T lymphocytes in the pathogenesis of PsA is, therefore,
      unlikely.

PMID- 10917159
TI  - Basaloid neoplasms in nevus sebaceus.
AB  - BACKGROUND: Nevus sebaceus (NS) (organoider nevus) may frequently be associated
      with the development of a number of benign and malignant neoplasms among which
      basaloid neoplasms are the most common. Histopathologic criteria for diagnosis
      and classification of basaloid proliferations arising in NS are still debated.
      Most previous investigators have considered them to represent mainly basal cell
      carcinomas (BCCs). On the contrary, a number of recent authors have proposed that
      most basaloid neoplasms in NS exhibit predominantly morphologic features implying
      benignancy, thus representing trichoblastomas (TBs). In this study, we attempted
      to characterize better the histopathologic features of basaloid neoplasms in NS
      in a large series based on current morphologic criteria. METHODS: Three-hundred
      and sixteen cases of NS seen over 19 years were consecutively sampled and
      reviewed for basaloid neoplasms. Twenty-four cases of basaloid neoplasms in NS
      were identified and categorized based on current histopathologic criteria either
      as TB or BCC. For comparison of histopathologic features, 37 solitary TB were
      also studied. RESULTS: Following histopathologic analysis, 22 cases were
      categorized as TB (91.6%, 10 males, 12 females; mean age 40.8 years, range 19-78
      years) and 2 cases as BCC (8.4%, 1 male, 1 female; 32 years and 40 years).
      Clinical features in both groups were generally similar. The lesions presented
      exclusively on the head and neck as skin colored to pigmented papules or nodules
      within NS (scalp in 19 TB cases and 1 BCC case; face in 2 TB cases and 1 BCC
      case; neck in 1 TB case). Histopathologically, TB in NS were characterized by
      smooth-bordered basaloid aggregations with either a nodular and/or a superficial
      pattern, abundant fibrous stroma with focal clefts within the stroma, and
      prominent features of limited follicular differentiation (rudimentary follicular
      germs in concert with papillae). In contrast, BCC in NS showed basaloid
      aggregations that vary markedly in size and shape, scant fibrous stroma, focal
      mucinous clefts between basaloid aggregations and surrounding stroma, and lack of
      prominent rudimentary follicular germs in concert with papillae. Remarkably,
      sections in a few cases of TB showed features occasionally found in BCCs but
      presently widely considered to be unspecific (e.g., ulceration, cystic
      degeneration, and focal clefts between basaloid aggregations and surrounding
      stroma). Two cases of TB in NS were associated with a sebaceoma and 1 case with a
      desmoplastic trichilemmoma. Follow-up data in 14 TB cases and 2 BCC cases (mean
      follow-up 28.8 months; range 1 to 160 months) revealed no local recurrences or
      distant metastases. CONCLUSION: Our study confirms that the vast majority of the
      basaloid neoplasms arising in NS show clear-cut morphologic criteria for TB,
      whereas only a few cases display histopathologic features consistent with BCC. In
      a minority of cases, basaloid neoplasms with overall morphologic features of TB
      may present problems in diagnosis when they exhibit a few histopathologic
      features traditionally associated with BCC or when they occur in combination with
      other adnexal neoplasms.

PMID- 10917160
TI  - Immunohistochemical localization of ornithine decarboxylase in skin tumors.
AB  - BACKGROUND: Ornithine decarboxylase (ODC) plays an important role in the
      biosynthesis of polyamines. Induction of ODC and polyamine synthesis has been
      demonstrated in neoplastic tumors and is thought to be related to the degree of
      malignancy. METHODS: In this study, we investigated a series of basal cell
      epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC), and
      metastatic tumors of the skin using an antibody against ODC for
      immunohistochemistry. RESULTS: Eight of 12 cases of BCE failed to show a positive
      reaction for ODC. In Bowen's disease, 5 of 13 cases diffusely showed positive
      reaction for ODC. Fourteen of 15 cases of SCC showed ODC expression, the
      intensity of which was decreased in the peripheral layer. At higher
      magnification, the distribution of ODC in the positive SCC cases showed granular
      and heterogenous patterns. Ten of 14 cases of metastatic skin tumors exhibited
      positive reactions, and well-differentiated adenocarcinomas tended to show more
      strongly positive than poorly-differentiated ones. CONCLUSIONS: These results
      support the conclusion that the intensity and the incidence of positive
      immunohistochemical staining for ODC correlate with the degree of cellular
      differentiation, and furthermore, that heterogenous distribution of ODC staining
      may be associated with heterogeneity of tumor cells.

PMID- 10917161
TI  - Keratotic melanocytic nevus: a clinicopathologic and immunohistochemical study.
AB  - BACKGROUND: Epidermal hyperplasia in melanocytic nevi is a common but little
      investigated phenomenon. METHODS: We prospectively examined all melanocytic nevi
      diagnosed in our department over an 8-month period, for the criteria of keratotic
      melanocytic nevus (KMN), namely the presence of marked epidermal hyperplasia with
      or without horn pseudocyst formation, hyperkeratosis, and papillomatosis. In
      addition to routine histologic review, we studied 12 representative cases with
      immunohistochemistry to examine expression of Ki-67, epidermal growth factor
      receptor (EGFR), Bcl-2, and Bax. RESULTS: From a total of 1,527 melanocytic nevi,
      95 were KMN (prevalence 6%). The average age was 34 years, with a male:female
      ratio of 1:2. The predominant location was the trunk (76%), followed by head and
      neck (20%), and extremities (4%). Clinical diagnoses were atypical nevus (44%),
      nevus not otherwise specified (43%), and others including seborrheic keratosis,
      acrochordon, and basal cell carcinoma. Two KMN were junctional, 44 compound, and
      49 intradermal. Twenty-three KMN (24%) had histologic features suggesting
      congenital onset, and 15 (16%) had mild to moderate dysplastic features. Two
      cases demonstrated induction of sebaceous glands. Significantly increased Ki-67
      expression was detected in the hyperplastic epidermis, particularly in deeper
      areas related to keratinous cysts and hair follicles. Bcl-2 and Bax (anti- and
      pro-apoptosis proteins, respectively) and EGFR were expressed similarly in both
      normal and hyperplastic epidermis overlying the KMN. CONCLUSIONS: KMN are
      commonly biopsied skin lesions, mostly located on the trunk. Many such lesions
      are clinically considered atypical, in contrast to their benign histologic
      appearance. The epidermal hyperplasia on top of KMN demonstrates increased
      cellular proliferation, in the context of adequately regulated apoptosis and EGFR
      expression. The cellular proliferation seems to commence in hair follicles.

PMID- 10917162
TI  - The carcinoembryonic antigen (CEA) family (CD66) expressed in melanocytic naevi
      is not expressed in blue naevuscell naevi in dendritic type.
AB  - BACKGROUND: Although sporadic reports have regarded the expression of the
      carcinoembryonic antigen (CEA) family in melanoma, there has been no information
      about the expression in precursor lesions of melanoma such as melanocytic naevi
      and blue naevi. METHODS: The expression was immunohistochemically studied in
      frozen biopsy specimens of 45 acquired and 16 congenital melanocytic naevi and 20
      blue naevi, using a panel of monoclonal and polyclonal antibodies that recognize
      different epitopes of CEA and related molecules. RESULTS: Members of the CEA
      glycoprotein family were strongly expressed in all of the subtypes of melanocytic
      naevus. A reduced expression of the CEA glycoproteins with increased dermal depth
      or acquisition of a spindled morphology of naevus cells was apparent. The
      expression was not seen in the present blue naevi and normal epidermal
      melanocytes. CONCLUSIONS: Although the significance of the expression was not
      clarified, this report has clearly demonstrated that the CEA family is strongly
      expressed in melanocytic naevi and immunoreactivity is divergent between
      melanocytic naevi and blue naevi and between dermal naevus cell types, suggesting
      that the expression may be altered with architectural changes in the melanocyte
      lineage cells.

PMID- 10917163
TI  - CGRP-immunoreactive nerves in prurigo nodularis--an exploration of neurogenic
      inflammation.
AB  - BACKGROUND: The present study has explored the localization and distribution of
      calcitonin gene-related peptide (CGRP)-immunoreactive (IR) nerve fibers in
      prurigo nodularis, especially emphasizing its relationships to mast cells and
      eosinophils, which all are important contributors to inflammation. METHODS: The
      exact localization of CGRP in the nerve fibers of prurigo nodularis lesional skin
      has been clarified by an ultrastructural immunogold labelling technique; and the
      relationships of CGRP-IR nerve fibers to tryptase-IR mast cells or eosinophil
      cationic protein (ECP)-IR eosinophils were also investigated by
      immunofluorescence double-labelling. RESULTS: This ultrastructural study has
      demonstrated that CGRP immunoreactivity is increased in the dense-core vesicles
      in the axons of the prurigo nodularis lesional skin; the axons which contain CGRP
      are, in addition, enlarged and have more dense-core vesicles than the axons which
      do not contain CGRP. The immunofluorescence investigation demonstrated that
      tryptase-containing mast cells and ECP-containing eosinophils also are
      significantly increased in the lesional skin. CONCLUSIONS: The results indicate
      that certain neurons increasingly express CGRP, which may dynamically result in a
      neurogenic inflammation in the lesional skin, through vasodilatation, and
      recruitment and regulation of inflammatory cells, e.g. eosinophils and mast
      cells.

PMID- 10917164
TI  - Cytokeratin expression of apocrine and eccrine poromas with special reference to
      its expression in cuticular cells.
AB  - BACKGROUND: There are no immunohistochemical studies on cytokeratin (CK)
      expression in large series of cases of apocrine poroma. In addition, detailed
      immunohistochemical analysis of cuticular cells, a specific type of constituent
      cells of poromas, has not been reported. METHODS: Using the avidin-biotin method,
      we compared immunostaining patterns of eleven different anti-CK antibodies in 12
      cases of apocrine and 21 cases of eccrine poromas, and normal adult skin.
      RESULTS: Poroid cells were exclusively positive for CK1/5/10/14, CK5/8 and CK14,
      which were expressed in the outer cells of normal dermal sweat ducts. Poroid
      cells were heterogeneously stained with anti-CK7, CK8/18, CK 10/11 and CK19
      antibodies, which reacted in the inner cells of dermal ducts and in the secretory
      cells of sweat glands. The cuticular cells showed constant expression of CK1/5/
      10/14 and CK10/11, and various expression patterns of CK5/8, CK6, CK7, CK14,
      CK8/18, CK17, and CK19. CONCLUSIONS: Based on the keratin immunohistochemistry,
      the neoplastic cells in eccrine and apocrine poromas are considered to be closely
      related to the cells of dermal sweat ducts. Also the cuticular cells are
      considered to occupy an intermediate spectrum between the inner and outer cells
      of the dermal ducts. Although it is difficult to differentiate apocrine poroma
      from eccrine poroma by keratin expression patterns alone, the data obtained here
      can be helpful in differentiation of apocrine poroma from other hair follicle
      related neoplasms.

PMID- 10917165
TI  - Lipid and giant cell poor necrobiotic xanthogranuloma.
AB  - An 88-year-old man over a 7-month period developed multiple yellow firm focally
      ulcerative papules and nodules over his face, neck and forearms. Seven skin
      biopsies showed a diffuse infiltrate of epithelioid histiocytes associated with
      areas of necrosis with neutrophilia. Two biopsies showed xanthogranulomatous
      foci, but cholesterol clefts, prominent giant cells or lymphoid aggregates were
      not evident. Necrosis with leukocytoclastic debris overshadowed the presence of
      hyaline necrobiosis. Ultrastructural examination and oil red-o stains on frozen
      sections revealed focal lipid vacuoles within histiocytes. A paraprotein was
      detected in the patient's serum. This presentation may represent a lipid and
      giant cell poor variant of necrobiotic xanthogranuloma (NXG) and may potentially
      lead to a delay in diagnosis.

PMID- 10917166
TI  - Ontogeny, differentiation and growth of the endocrine pancreas.
AB  - The pancreas develops from the primitive foregut endoderm, which differentiates
      into ductal, acinar and endocrine cells. This complex process is probably
      replicated in the adult pancreas when endocrine cell renewal is required, as may
      be the case in diabetes mellitus. This review describes what is known about the
      morphogenesis of the endocrine pancreas during ontogeny and the mechanisms
      regulating its differentiation and growth.

PMID- 10917167
TI  - Cytomegalovirus genome and the immediate-early antigen in cells of different
      layers of human aorta.
AB  - A number of data suggest that reactivation of cytomegalovirus (CMV) latent in
      arterial wall cells may contribute to atherogenesis; however, there is no direct
      evidence available. To address this issue, we have examined, using in situ
      hybridization or immunohistochemical staining, the frequency of occurrence of
      cells containing viral genome and of those expressing the IE 70 viral antigen in
      the endothelial layer and in deeper layers of human aortas with or without
      visible atherosclerotic lesions. Using endothelial cell cultures or tissue
      endothelial preparations, we found CMV-hybridizing endothelial cells in 6 of 8
      grossly normal aortas and in 16 of 18 lesioned aortas. Antigen-positive
      endothelial cells were detected in 1 of 5 grossly normal vessels and in 6 of 7
      lesioned vessels. Infected endothelial cells were abundant in areas adjacent to
      orifices of intercostal arteries of grossly normal aortas and in fatty spots of
      lesioned aortas, but no infected endothelial cells were observed in most plaques
      examined. In paraffin sections of grossly normal vessels, we detected CMV genome
      in cells adjacent to lumen and in cells randomly scattered through subendothelial
      intima and the media; however, no immunoreactive viral protein was found in the
      same tissue samples. In sections of lesioned vessels, clusters of CMV-hybridizing
      cells were found in the media in addition to infected cells randomly scattered
      through the intima and the media. In these samples of lesioned vessels, viral
      antigen was detected in cells adjacent to lumen and in cells clustered at the
      intima/media border. We found antigen-positive cells in grossly normal areas of
      lesioned aortas and in fatty lesions, but not in plaques of the same vessels. The
      data suggest that accumulation of the immediate-early CMV antigen in cells of
      endothelial layer and development of antigen-positive cell clusters in deeper
      layers of vascular wall accompany early atherogenic events in human aorta.

PMID- 10917168
TI  - Immunoreactivity for latent membrane protein 1 of Epstein-Barr virus in nevi and
      melanomas is not related to the viral infection.
AB  - Epstein-Barr virus (EBV) is a human herpes virus with oncogenic potential,
      associated with several malignancies. The EBV-encoded latent membrane protein 1
      (LMP1) is one of nine proteins regularly expressed in virally infected and
      immortalised B lymphocytes. We now document the consistent immunoreactivity for
      LMP1 in 90% of 65 nevi and melanomas, using the monoclonal antibody cocktail CS1
      4. The immunocytochemical findings, however, were not confirmed using reverse
      transcription polymerase chain reaction (RT-PCR) experiments, which failed to
      demonstrate any actual expression of LMP1 mRNA. In situ hybridisation for EBV
      encoded RNAs (EBERs 1 and 2) and PCR amplification of EBV genomic sequences also
      failed to document any viral infection. Several normal and neoplastic human
      tissues have also been immunostained for LMP1, without any positive staining,
      with the exception of a minor percentage of skin melanocytes and of normal blasts
      of the myeloid and erythroid lineages. We conclude that the vast majority of nevi
      and melanomas express a still uncharacterised molecule, cross-reacting with anti
      LMP1 (CS1-4) antibodies, which may be considered a consistent marker of
      melanocytic proliferations. The immunoreactivity of normal and neoplastic human
      tissues for the anti-LMP1 reagent should not be taken as evidence of EBV
      infection.

PMID- 10917169
TI  - Evidence of M cells as portals of entry for antigens in the nasopharyngeal
      lymphoid tissue of humans.
AB  - The nasopharyngeal tonsils (adenoids) are prominent components of human nasal
      associated lymphoid tissues (NALT). However, the role of the nasopharyngeal
      tonsils in antigen uptake for initiation of the mucosal immune response is
      unknown. The aims of this study were to describe the ultrastructure and function
      of the M cells of the human nasopharyngeal tonsils and to clarify their capacity
      for antigen uptake. Tissues obtained from eight patients undergoing adenectomy
      were examined by light and electron microscopy. Lymphoepithelium covers the
      nasopharyngeal lymphoid tissue and consists of ciliary epithelium, non-ciliary
      epithelial cells, M cells, goblet cells, and many intraepithelial lymphoid cells.
      M cells have irregular and broad cytoplasm-containing microvilli on their surface
      and small vesicles in their cytoplasm. Many lymphoid cells were enfolded by M
      cells. The uptake of horseradish peroxidase (HRP) in the tissue in organ culture
      was studied using histochemical techniques. Excised adenoid tissue was incubated
      in RPMI 1640 culture media with HRP for 10, 30, and 60 min. HRP which had adhered
      to the surface was taken up in vesicles and then transported in vesicles and
      tubules by M cells. The M cells of nasopharyngeal lymphoid tissue were
      ultrastructurally and functionally similar to those in human Peyer's patches and
      colonic lymphoid follicles. These findings indicate that NALT bears similarities
      to the gut-associated lymphoid tissue, and its antigen uptake capacity may be
      important for initiation of immunity in the upper aerodigestive tract.

PMID- 10917170
TI  - Mesangial cell necrosis in Thy 1 glomerulonephritis--an ultrastructural study.
AB  - Cell death is central to many physiological and pathological processes. As tissue
      reactions to the two forms of cell death, necrosis and apoptosis, differ, it is
      critical to distinguish between them. Although ultrastructure is still the
      definitive means of assessing this, there are very few in vivo studies.
      Administration of anti-Thy 1 antibody in rats is a model of acute glomerular
      mesangial cell death due to their expression of the Thy 1.1 epitope. The nature
      of this process is unclear; apoptosis was suggested from early morphological
      studies and recent in vitro effects of anti-Thy 1.1 antibody. We have re-examined
      the changes by electron microscopy, and identified a process of cell necrosis
      starting within 30 min of anti-Thy 1.1 antibody administration. Although there
      was chromatin condensation, the necrotic features distinctive from apoptosis
      were: loss of nuclear membranes, cell swelling and degeneration of cytoplasmic
      organelles, with liberation of chromatin and organelles into the interstitium
      causing acute inflammation without phagocytic uptake of apoptotic bodies. These
      findings accord with the known complement dependence of this model.
      Ultrastructure is a valuable means of differentiating between in vivo necrosis
      and apoptosis and this is important for understanding the pathogenesis of injury
      and subsequent tissue responses.

PMID- 10917171
TI  - CD44 expression in soft tissue sarcomas.
AB  - Recent studies have shown that expression of alternatively splicing variants of
      CD44 is correlated with prognosis for several kinds of malignant tumors. However,
      little is known about the expression of CD44 standard and variant isoforms in
      soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant
      fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas
      (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The
      monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of
      CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression
      pattern of CD44H and CD44 variant exons and assessed the relation between
      expression of CD44s and metastasis-free survival rates (MFSR) of patients with
      soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but
      none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and
      v9 (9/47) are relatively common types of variant isoforms in soft tissue
      sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in
      low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free
      survival of patients with soft tissue sarcomas.

PMID- 10917172
TI  - Expression of the extracellular matrix protein tenascin in laryngeal epithelial
      lesions: correlation with fibronectin, CD44, cathepsin D and proliferation
      indices.
AB  - Tenascin (TN) is an extracellular matrix glycoprotein expressed in areas of
      epithelial-mesenchymal interactions during embryogenesis and in neoplasia. We
      studied the expression of TN in a series of 35 squamous cell invasive carcinomas
      of the larynx, 13 in situ carcinomas, 41 cases of dysplasia, 10 papillomas and 18
      cases of keratosis using the monoclonal antibody TN2 on paraffin-embedded tissue.
      TN expression was correlated with the expression of fibronectin, CD44 and
      cathepsin D (CD) proteins, with the proliferation indices Ki-67 and proliferating
      cell nuclear antigen (PCNA) as well as with conventional clinicopathological
      variables. Malignant tumours showed a significantly greater stromal TN staining
      than benign lesions. In invasive carcinomas, the immunoreactivity was
      statistically higher than that in situ (P=0.01), dysplastic lesions (P<0.0001),
      papillomas (P=0.004) and keratosis (P<0.0001). A statistically significant
      difference of TN expression between in situ and dysplastic lesions was observed
      (P=0.001). In invasive lesions, TN expression was statistically correlated with
      CD44 expression (P=0.02) and a trend for correlation with CD of tumour cells and
      fibronectin expression was found (P=0.06 and P=0.09, respectively). The
      relationship of TN expression with the histological grade and the proliferative
      activity was insignificant. In conclusion, stromal TN expression may be involved
      in the complex mechanism of development of laryngeal lesions and may help to
      predict the risk of progression of pre-cancerous lesions to cancer.

PMID- 10917173
TI  - Evaluation of the applicability of the gastric carcinoma risk index for
      intestinal type cancer in Japanese patients infected with Helicobacter pylori.
AB  - The gastric carcinoma risk index is a histological criteria to Helicobacter
      pylori-infected patients with a high risk of gastric cancer. The aim of this
      study was to examine the applicability of this index for the intestinal-type
      gastric cancer in Japanese patients with H. pylori infection. In 55 patients with
      early intestinal-type gastric cancer and 69 control subjects, we calculated the
      gastric cancer risk index score by evaluating the grade of mononuclear cell (MNC)
      and polymorphonuclear cell (PMN) infiltration and the presence of intestinal
      metaplasia. The gastric cancer index score was significantly higher in patients
      with gastric cancer (P<0.01). The presence of intestinal metaplasia was
      significantly more frequent in cancer patients than in controls, while
      infiltration of MNCs or PMNs in the corpus was not different in the two groups.
      Within the gastric cancer risk index, the presence of intestinal metaplasia was
      the only criteria associated with the development of intestinal-type gastric
      cancer in Japan. The gastric cancer risk index may not be applicable to identify
      H. pylori-positive patients at high risk of developing intestinal-type gastric
      cancer in Japan.

PMID- 10917174
TI  - Lack of Pseudomelanosis coli in colonic adenomas suggests different pathways of
      apoptotic bodies in normal and neoplastic colonic mucosa.
AB  - Pseudomelanosis coli is characterized by pigment deposition in the lamina propria
      and caused by increased epithelial apoptosis. Pseudomelanosis coli is absent in
      colonic neoplasia. The aim of our studies was to investigate this phenomenon in
      more detail. Apoptotic fragments of epithelial cells and their distribution, cell
      proliferation (Ki-67, MIB 1 immunostaining), macrophages (CD68 immunostaining),
      Bcl-2 expression and apoptosis [terminal-deoxynucleotidyl-transferase mediated
      dUTP fluorescein nick end labeling (TUNEL) assay] were studied in adenomas
      arising in normal and melanotic colonic mucosa, in normal colonic mucosa and
      colonic mucosa with pseudomelanosis alone. In adenomas, we found 7.0 apoptotic
      bodies per 100 epithelial cells in the epithelial layer and only 0.2 apoptotic
      bodies per high power field (HPF) in the lamina propria. In contrast, in
      melanotic mucosa 1.7 apoptotic bodies per 100 epithelial cells in the epithelial
      layer and 2.5 per HPF in the lamina propria were found. Our results show that
      apoptotic fragments remain in the neoplastic (adenomatous) epithelium and do not
      reach (at least in higher amounts) the lamina propria. They can, therefore, not
      contribute to the development of pseudomelanosis in these lesions. However,
      macrophages are diminished in adenomas. Proliferation (Ki-67) and also Bcl-2
      expression are highly increased in adenomas. The pathway of mucosal macrophages
      is also discussed.

PMID- 10917175
TI  - Alterations of basement membrane in di-isopropanolnitrosamine-induced
      carcinogenesis of the rat thyroid gland: an immunohistochemical study.
AB  - Alterations of basement membrane (BM) in di-isopropanolnitrosamine (DIPN)-induced
      carcinogenesis of the rat thyroid gland were examined by means of
      immunohistochemical localization of collagen type IV (CN-IV), laminin (LN), and
      fibronectin (FN) in prenodular and nodular thyroid lesions, correlating with the
      morphogenesis and proliferative activity of these lesions. Adult male rats of the
      Wistar strain were injected s.c. in the back with DIPN, and the thyroid glands
      were removed at the 15th and 30th week of treatment. Each of 133 thyroid lesions
      was histochemically analyzed. The follicular epithelial BM as revealed by CN-IV
      and LN was discontinued or completely lost during the progression of thyroid
      lesions from pre-nodular to nodular lesions and finally overt carcinomas. At the
      same time, the BM of vascular endothelial cells demonstrated a loss of dense
      capillary networks of follicles, a sinusoidal dilatation and, predominantly in
      carcinomas, development of interstitial-type blood vessels. However, FN, which
      was hardly stained in the normal thyroid tissue, was remarkably deposited in the
      interstitium of invasive carcinomas. These observations strongly suggested that
      alterations of BM structure play a key role in the morphogenesis of rat thyroid
      tumors, and that the expression of FN is an important step in the invasive growth
      of thyroid tumors.

PMID- 10917176
TI  - Expression of bcl-2, Bax and Fas in oxyphil cells of Hashimoto thyroiditis.
AB  - Immunoreactivity for bcl-2, Bax and Fas was analysed in 16 cases with Hashimoto
      thyroiditis. Bcl-2-expression was constantly seen in regular thyrocytes and in
      the mantle-zone of lymphofollicular infiltrates. However, thyrocytes in the
      vicinity of lymphoid infiltrates and, especially, mitochondria-rich oxyphil cells
      exhibited reduced staining or none at all for bcl-2. Bax was found to be weakly
      reactive or negative in normal thyrocytes and was not up-regulated in bcl-2
      deficient epithelial cells. In contrast, expression of Fas was markedly increased
      both in typical thyrocytes and in oxyphil cells within areas of lymphocytic
      infiltration. In conclusion, focal lack of bcl-2 expression together with up
      regulation of Fas is a constant feature of Hashimoto thyroiditis. The reaction
      pattern of oxyphil cells is identical to that of affected typical thyrocytes
      without proliferation of mitochondria. Loss of bcl-2 with up-regulation of Fas is
      therefore likely to precede oncocytic change. Whether these alterations are
      involved in the process of oncocytic transformation remains to be clarified,
      however.

PMID- 10917177
TI  - Effect of etoposide on experimental testicular teratoma in 129/SvJ mice.
AB  - To study the effects of etoposide on experimental testicular teratoma in 129/SvJ
      mouse we analysed the tumour growth, differentiation, apoptosis and the
      localisation of mdr1 P-glycoprotein (mdr1-Pgp). In this model the implanted
      gonadal ridges developed into testicular teratomas in 17 out of 56 implanted
      testes (30%) and in 14 out of 28 mice (50%). The tumour-bearing mice were treated
      with etoposide on 4 successive days either 4 weeks or 6 weeks after implantation,
      and killed 7 days after the last dose. The mice in the control groups did not
      receive etoposide. The teratomas consisted mainly of neural tissue. The etoposide
      treated 4-week teratomas, but not the 6-week teratomas, were significantly
      smaller than those in the corresponding control groups. The density of apoptotic
      cells and the distribution of the mdr1-Pgp were not altered by etoposide. The
      decreased proportion of immature neuroectodermal tissue components was observed
      in all treated teratomas, converting the histology towards that of a mature
      teratoma. In addition, a low proportion of immature tissue components was
      frequently combined with a low density of apoptotic cells. In conclusion,
      etoposide decreased the immature tissue components of teratomas, while mature
      tissues remained unaffected. These results may have clinical relevance in man,
      since they confirm that postchemotherapy mature teratomas cannot be treated with
      chemotherapy. Despite benign histology, the human residual tumours have a
      significant malignant potential and require complete surgical excision and close
      surveillance.

PMID- 10917178
TI  - Respiratory syncytial virus-induced chronic bronchiolitis in experimentally
      infected calves.
AB  - Human (RSV) and bovine (BRSV) respiratory syncytial virus cause similar
      infections of the lower respiratory tract. Therefore, experimentally infected
      calves are suited to the study of RSV-induced chronic bronchiolitis. Colostrum
      fed calves aged 17-24 days were successfully infected with BRSV. BRSV strain 375
      was applied as an aerosol on 4 consecutive days. Clinical symptoms were already
      evident on the 1st day after infection. The calves were necropsied 12 weeks after
      the first infection. Focal severe chronic bronchiolitis with atelectasis and
      focal bronchiolitis obliterans were demonstrated. The bronchiolar lumina were
      filled with secretion. Transmission electron microscopy revealed an alteration of
      the ciliogenesis and partial loss of cilia. Immunhistochemically virus P protein
      could still be detected, mainly in the epithelial cells of the inflamed
      bronchioli.

PMID- 10917179
TI  - Primary vaginal adenocarcinoma arising from the metanephric duct remnant.
AB  - Primary vaginal adenocarcinoma unrelated to in utero exposure to
      diethylstilbestrol (DES) is very uncommon. We report a case of 65-year-old
      Japanese woman who presented with primary adenocarcinoma in the anterior wall of
      the vagina, where the left ureter-like metanephric duct remnant abnormally
      terminated. Histological examination in serial sections revealed the direct
      connection between the carcinoma and the metanephric duct remnant. Moreover, the
      remnant epithelium showed varying degrees of dysplastic changes, including
      carcinoma in situ in close proximity to the carcinoma. This patient also had a
      bicornate uterus and left renal aplasia. To our knowledge, this is the first
      reported case of a primary vaginal adenocarcinoma arising from the metanephric
      duct remnant. Although the precise mechanism involved in carcinogenesis in this
      clinicopathological setting remains unknown, adenocarcinoma should be included in
      the differential diagnosis of vaginal tumors in patients with renal aplasia
      and/or an ectopic termination of the ureter or metanephric duct remnant,
      especially when the tumor is in the anterior wall.

PMID- 10917180
TI  - Unusual prostatic adenocarcinoma with endocrine basophilic FSH-immunoreactive
      cells.
AB  - We report an unusual variant of prostatic adenocarcinoma with marked endocrine
      differentiation (mixed endocrine-exocrine adenocarcinoma). Endocrine cells
      accounted for 60% of the tumour cells, were positive with silver impregnation and
      for chromogranin A, synaptophysin, and neuron-specific enolase, and coexpressed
      the exocrine antigens prostatic acid phosphatase and prostatic-specific antigen.
      Most of the endocrine cells were basophilic with haematoxylin-eosin and proved
      immunoreactive for alpha subunit of human chorionic gonadotropin and follicle
      stimulating hormone. The remaining endocrine cells were represented by
      eosinophilic cells positive for serotonin, and by calcitonin and serotonin
      immunoreactive cells not identifiable in haematoxylin-eosin-stained sections. On
      ultrastructural analysis, two types of endocrine cells were identified. The most
      frequent cell type showed abundant cytoplasmic round, electron-dense
      neurosecretory granules, either small (212+/-44 nm) or large (471+/-114 nm),
      resembling those of gonadotropic pituitary cells. The second type of endocrine
      cells contained irregular electron-dense granules similar to those of serotonin
      storing enterochromaffin cells.

PMID- 10917181
TI  - Randomized trial of N-butyl-2-cyanoacrylate compared with injection of hypertonic
      saline-epinephrine in the endoscopic treatment of bleeding peptic ulcers.
AB  - BACKGROUND AND STUDY AIMS: Theoretically, the injection of cyanoacrylate may be
      effective for peptic ulcer bleeding, but randomized clinical trials are rare. The
      aim of this study was to compare the efficacy of N-butyl-2-cyanoacrylate
      (Histoacryl) and hypertonic saline-epinephrine (HSE) in the endoscopic treatment
      of major peptic ulcer hemorrhage. PATIENTS AND METHODS: A total of 126 patients
      with major peptic ulcer hemorrhage and active bleeding or a nonbleeding visible
      vessel were randomly allocated to endoscopic injection with HSE (63 patients;
      group 1) or to injection with Histoacryl (63 patients; group 2). The two groups
      were well matched for age, sex, initial hemoglobin values, ulcer size and
      location, and bleeding stigmata. RESULTS: Initial hemostasis was achieved in 58
      cases (92.1%) in group 1 and in 60 cases (95.2%) in group 2 (P=0.717). Rebleeding
      rates were 16 of 58 in group 1 and seven of 60 in group 2 (P=0.051). There were
      no significant differences regarding the rates of permanent hemostasis (51 of 63
      in group 1 vs. 57 of 63 in group 2, P=0.203), emergency surgery (seven of 58 in
      group 1 vs. three of 60 in group 2, P=0.200), or hospital mortality due to
      bleeding (0 in group 1 and 0 in group 2). With regard to the rebleeding rate,
      there was a significant difference between group 1 and group 2 in the subgroup
      with active arterial bleeding (11 of 26 in group 1 and four of 29 in group 2,
      P=0.039) but not in the subgroup with a nonbleeding visible vessel (five of 32 in
      group 1 and three of 31 in group 2, P=0.708). There were no statistically
      significant differences in hemostatic results between the two treatment groups in
      the subgroups with gastric ulcers or duodenal ulcers. Although no complications
      followed HSE therapy, arterial embolization with infarction occurred in two
      patients in the Histoacryl group, of whom one died. CONCLUSIONS: Compared with
      HSE injection, Histoacryl injection showed no statistically significant
      differences in hemostatic results, except for decreasing the rebleeding rate in
      the patients with active arterial bleeding. However, the use of Histoacryl to
      control peptic ulcer bleeding should be reserved as a last resort before surgery,
      because of possible embolic complication.

PMID- 10917182
TI  - Bucrylate treatment of bleeding gastric varices: 12 years' experience.
AB  - BACKGROUND AND STUDY AIMS: For several years now there has been an increasingly
      widespread use of a tissue adhesive in the treatment of bleeding gastric varices
      to achieve rapid, safe control of hemostasis and prevent rebleeding. In this
      study we report on our experience with the use of Bucrylate (Hystoacryl) for the
      treatment of gastric varices over a period of more than a decade. PATIENTS AND
      METHODS: Since 1988, 174 cirrhotic patients with actively bleeding gastric
      varices have been admitted to our department, where they received emergency
      treatment with injections of Bucrylate. Any associated nonbleeding esophageal
      varices were subjected to traditional sclerotherapy in combination with the
      Bucrylate treatment. The gastric varices were subdivided into four distinct
      groups according to the method advocated by Sarin in 1989. The patients underwent
      weekly sclerotherapy sessions until their varices were eradicated, and the follow
      up with a mean of 36 months (range 9-90 months) consisted of endoscopy at 3, 6,
      and 12 months during the first year and then yearly checks to confirm
      obliteration of the varices. RESULTS: The hemostasis (97.1%), early rebleeding
      (15.5%), and hospital mortality (19.5%) rates of the patients with bleeding
      gastric varices, treated with the tissue adhesive, were very similar to those of
      patients treated for esophageal varices over the same period (98.1%, 13.0%, and
      16.4%, respectively). The most frequent cause of death at 30 days was liver
      failure (76% of cases), followed by hemorrhagic shock (8.8%), and other less
      frequent causes. Sclerotherapy achieved obliteration rate for gastric varices (70
      75%) similar to that for esophageal varices in those patients with portal
      hypertension due to intrahepatic block (alcoholic and posthepatitis cirrhosis),
      but a rate of only 32% in the group of patients with prehepatic block
      (splenoportomesenteric thrombosis), where surgery proved more effective (69%).
      The medium- and long-term survival rates depended on the stability of the
      patients' liver conditions, on rapid, effective control of variceal hemostasis,
      and on complete, lasting obliteration of the gastric varices. CONCLUSIONS: The
      use of Bucrylate in emergency sclerotherapy achieved results in bleeding gastric
      varices on a par with those obtained in esophageal varices in cases of alcoholic
      and posthepatitis cirrhosis. The group of patients with portal hypertension due
      to prehepatic block (splenoportal thrombosis) showed no benefit from
      sclerotherapy in terms of obliteration of gastric varices, but benefited from
      elective surgery. The choice of the obliterating treatment indicated may be
      facilitated by classifying gastric varices into distinct groups on the basis of
      anatomicotopographic criteria.

PMID- 10917183
TI  - Biliary varices on endoscopic ultrasonography: clinical presentation and outcome.
AB  - BACKGROUND AND STUDY AIMS: Bile duct varices are not a well-recognized feature of
      portal venous obstruction. The aim of the present study was to describe the
      clinical and endosonographic features of biliary involvement in patients with
      extrahepatic portal venous obstruction (EPVO). PATIENTS AND METHODS: A
      retrospective study was conducted of the clinical features, outcome, and
      endosonographic findings (using Olympus EUM-3 or EUM-20 probes) in 21 patients
      with EPVO and endosonographic features of biliary varices. Biliary varices were
      defined as multiple, large, serpiginous, anechoic vascular channels in and/or
      surrounding the extrahepatic biliary tracts. RESULTS: Biliary varices have not
      previously been visible using conventional imaging methods (computed tomography
      and ultrasonography). They were identified using EUS in the wall of the common
      bile duct in 16 patients (76%), surrounding the common bile duct (CBD) in 11
      patients (52%), and in the gallbladder in nine (43%). The varices were the cause
      of obstructive jaundice in three of the 21 patients (14%), but only when they
      were in the wall of the CBD. Two of these patients were treated using
      portosystemic shunting, and the other received a biliary endoprosthesis. The EUS
      examination also provided evidence of unrecognized pancreatic or biliary tumors
      in three other patients with EPVO of undetermined origin. CONCLUSIONS: EUS can
      serve to diagnose biliary varices in patients with EPVO and jaundice. Although
      biliary varices are mainly asymptomatic, they may cause obstructive jaundice when
      they are located in the wall of the CBD. EUS can also detect unrecognized
      malignant tumors in patients with EPVO of undetermined origin.

PMID- 10917184
TI  - Rectosigmoid endometriosis: endoscopic ultrasound features and clinical
      implications.
AB  - BACKGROUND AND STUDY AIMS: The main area of the gastrointestinal tract affected
      by deep pelvic endometriosis is the rectosigmoid colon in 3-37% of cases. Due to
      the risk of infiltration and the clinical symptoms of endometriosis, with pain
      and infertility, the condition may require surgical resection. Preoperative
      imaging diagnosis of rectosigmoid involvement is therefore important. Rectal
      endoscopic ultrasonography (EUS), which is already used for the staging of
      anorectal carcinoma and submucosal lesions, may be a promising technique for this
      indication. The present study was conducted in order to describe the
      endosonographic appearance of rectosigmoid endometriosis, and to define the
      potential relevance of the technique to the choice of resection method. PATIENTS
      AND METHODS: Between 1993 and 1997, 46 women (mean age 31) with deep pelvic
      endometriosis underwent imaging investigations and surgical resection. The
      clinical and imaging findings, and the surgical and histological features
      identified--mainly with regard to infiltration of the rectal wall--were compared
      retrospectively. The impact of the EUS findings on the decision on whether or not
      to carry out resection, either by laparoscopy or open abdominal surgery, was also
      examined. RESULTS: When there was deep pelvic endometriosis with suspected rectal
      wall infiltration, EUS showed normal anatomy in nine patients, endometriotic
      lesions without rectal wall infiltration in 12, and typical rectal infiltration
      in 25. The lesions were confirmed by the surgical findings during therapeutic
      laparoscopy (n = 22) and laparotomy (n = 25), as well as by clinical follow-up.
      Rectal wall infiltration, demonstrated in all cases using EUS, had initially been
      suspected on the basis of clinical examinations, rectoscopy, barium enema,
      computed tomography, and magnetic resonance imaging in 62%, 50%, 33%, 67% and 66%
      of cases, respectively. CONCLUSIONS: EUS is a simple and noninvasive technique
      capable of correctly diagnosing rectal wall infiltration in deep pelvic
      endometriosis. It may be helpful in determining the choice between laparoscopy
      and laparotomy when complete resection is indicated.

PMID- 10917185
TI  - Endoscopic ultrasonography-guided fine-needle cytodiagnosis of mediastinal
      metastases from renal cell cancer.
AB  - BACKGROUND: Endoscopic ultrasonography (EUS) has become the investigation of
      choice for the evaluation of the mediastinum. Lung and mediastinum are amongst
      the common sites of metastases from renal cell cancer (RCC). We diagnosed
      metastatic RCC in mediastinal lymph nodes by EUS-guided fine-needle aspiration
      (FNA) cytology. METHODS: A total of 111 patients with mediastinal lymph nodes had
      undergone EUS-FNA using a linear array echo endoscope and a 170 cm, 22 G GIP
      needle consecutively. Smears were prepared, air-dried, and sent to an independent
      cytologist. RESULTS: Seven patients (all males, mean age 64.8 years, range 45-72)
      were diagnosed cytologically to have metastatic RCC. Three patients had been
      diagnosed with RCC in the past (2, 7, and 17 years ago) while in the others, this
      was primarily diagnosed on the basis of EUS-FNA. The EUS features of these
      mediastinal RCC metastases include irregular lesions with inhomogenous
      echotexture, measuring 2.8 cm (median; range 1.0-4.5) located predominantly in
      the posterior mediastinum. CONCLUSION: EUS-FNA diagnosis of metastatic RCC is
      safe and feasible. It is especially useful in the evaluation of the mediastinum
      for suspected metastases. Cytology examination results in combination with
      clinical features could suggest the site of origin of the primary, assisting in
      further management.

PMID- 10917186
TI  - Laparoscopic findings in an adult case of Alagille syndrome.
AB  - Laparoscopic findings in a 32-year-old woman presenting with Alagille syndrome
      are reported. The liver surface showed a segmental whitish discoloration on the
      surface of both lobes with a transverse sulcus which was not stained enough after
      an intravenous injection of indocyanine green (ICG). These findings suggested an
      acquired bile duct injury in addition to a congenital anomaly of the bile duct in
      this patient.

PMID- 10917188
TI  - Use of esophagectomy to treat recurrent hyperplastic tissue obstruction caused by
      multiple metallic stent insertion for corrosive stricture.
AB  - We report a case of a 75-year-old woman who received repeated metallic stent
      insertion for corrosive esophageal injury. She underwent esophagectomy and
      gastric tube reconstruction about 3 years after injury because both stents were
      occluded in turn by overgrowth of granulation tissue. The gross and microscopic
      changes of the esophagus secondary to prolonged stent insertion are described. In
      the literature, no reports of similar cases have been recorded. Our limited
      experience revealed that using metallic stents to treat benign esophageal
      stricture should be handled very cautiously because of the complications which
      can commonly occur and are difficult to manage. Repeated stent insertion,
      although effective for temporarily relieving dysphagia, is ineffective in the
      long run and can create complications. We suggest that the feasibility of
      esophagectomy should be evaluated after the improvement of the general condition
      of the patient.

PMID- 10917187
TI  - Penetration by a giant gastric ulcer induced by a nonsteroidal anti-inflammatory
      drug.
AB  - A patient presented with penetration by a giant gastric ulcer resulting from
      treatment with a nonsteroidal anti-inflammatory drug. A test for Helicobacter
      pylori proved negative. Treatment with a combination of an inhibitor of gastric
      acid secretion and prostaglandin substitution therapy with misoprostol resulted
      in closure of the perforation and cicatrization of the gastric ulcer without the
      need for laparotomy.

PMID- 10917189
TI  - Pseudotumor of the sigmoid mimicking carcinoma.
AB  - On colonoscopy, the macroscopic aspect of a lesion is an important criterion for
      the differential diagnosis. We present a case of an apparently malignant tumor in
      the sigmoid. Histological investigation failed to support the diagnosis made from
      the gross appearance seen on colonoscopy. After surgical resection, the lesion
      turned out to be a reactive pseudotumor caused by fibroepithelial hyperplasia
      related to a severe diverticulitis with perforation of the intestinal wall.

PMID- 10917190
TI  - International Workshop on the clinical impact of endoscopic ultrasound in
      gastroenterology.

PMID- 10917191
TI  - An elderly man with a postcholecystectomy bile leak.

PMID- 10917192
TI  - How can we reduce complication rates and enhance success rates in Billroth II
      patients during endoscopic retrograde cholangiopancreatography?

PMID- 10917194
TI  - Endoscopic resection of two duodenal carcinoid tumors.

PMID- 10917193
TI  - Endoscopic resection of coexisting superficial carcinoma and a retention cyst.

PMID- 10917195
TI  - Large splenic artery aneurysm mimicking a gastric submucosal tumor.

PMID- 10917196
TI  - Management of stent overgrowth in a patient with Crohn's oesophagitis by argon
      plasma coagulation.

PMID- 10917197
TI  - Images in focus. Carcinoma with unknown primary tumor syndrome with mucosal
      metastasis in the duodenum mimicking angiodysplasia.

PMID- 10917198
TI  - Images in focus. An accessory gallbladder (double gallbladder) with an accessory
      cystic duct.

PMID- 10917199
TI  - Increased non-major histocompatibility complex-restricted lytic activity in
      melanoma patients vaccinated with cytokine gene-transfected autologous tumor
      cells.
AB  - Genetically modified antitumoral vaccines focus on eliciting or increasing the T
      cell-mediated antitumoral response. Little is known about non-major
      histocompatibility complex-restricted responses. In two phase I studies, we have
      immunized advanced melanoma patients with either interleukin-7 (IL-7) gene
      transfected or IL-12 gene-transfected, autologous, irradiated melanoma cells. To
      monitor the immune response, peripheral blood mononuclear cells were collected
      before the first vaccination and 2 weeks after the third vaccination. Spontaneous
      lytic activity and lymphokine-activated killer (LAK) activity after a 5-day
      culture in the presence of 1000 U/mL IL-2 against autologous and against
      allogeneic melanoma cells were measured. In parallel, a precursor cytotoxic T
      cell frequency analysis was performed using a 25-day limiting dilution analysis
      assay. A total of 10 of 14 immunologically evaluable patients demonstrated a
      marked increase in LAK activity, and 7 of 14 showed increased spontaneous lytic
      activities against autologous melanoma cells after three vaccinations.
      Remarkably, two patients with a good clinical performance status (Karnofsky index
      of >70; Multitest Merieux of >13.4 mm/3) and -the highest cytotoxic T-lymphocyte
      (CTL)-response after vaccination showed the only clear decrease in LAK and
      spontaneous lytic activity. Otherwise, three patients with no detectable CTL
      response after vaccination demonstrated an increase in LAK activity and the
      strongest increase in the autologous spontaneous lytic activity. This group of
      patients was associated with a poor clinical performance status (Karnofsky index
      of <70; Multitest Merieux of <4 mm/1) and with no clinical response. In
      conclusion, in accordance with other studies, a good clinical and immunological
      performance status appears to be the prerequisite for a successful CTL response.
      However, even strong non-major histocompatibility complex-restricted responses
      could be generated in patients with reduced clinical performance in vaccination
      therapies with gene-transfected autologous tumor cells.

PMID- 10917200
TI  - Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by
      induction of apoptosis.
AB  - Gene therapy designed to initiate apoptotic cell death provides a potentially
      effective method to treat cancer. A prerequisite for this approach is the
      identification of genes that function in distinct apoptotic pathways. Although
      apoptotic pathways initiated by receptors such as tumor necrosis factor receptor
      1 are well characterized, little is known about apoptotic pathways initiated
      within the nucleus in response to genotoxic stress. We have demonstrated
      previously that the nuclear, death domain-containing protein p84N5 can induce
      apoptosis upon transfection into cells, suggesting that it may play a role in an
      apoptotic pathway initiated within the nucleus. To test the possibility that N5
      could be used in the gene therapy of cancer, we have generated a recombinant
      adenovirus engineered to express N5 and tested the effects of viral infection on
      the growth and tumorigenicity of tumor cells. N5 adenovirus infection
      significantly reduced the proliferation and tumorigenicity of breast, ovarian,
      and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were
      mediated by an induction of apoptosis as indicated by DNA fragmentation in
      infected cells. The results suggest that the N5 cDNA is a candidate for the gene
      therapy of cancer.

PMID- 10917202
TI  - Inhibition of LncaP prostate cancer cells by means of androgen receptor antisense
      oligonucleotides.
AB  - Currently available methods for treatment of human prostatic carcinoma aim to
      inactivate the androgen receptor (AR) by androgen deprivation or blockade with
      anti-androgens. Failure of endocrine therapy and tumor progression is
      characterized by androgen-independent growth despite high levels of AR expression
      in metastatic disease. We inhibited AR expression in LNCaP prostate tumor cells
      by using antisense AR oligodeoxynucleotides (ODNs) and explored whether antisense
      AR treatment would be conceivable as a therapy for advanced prostate cancer.
      Among the various AR antisense ODNs tested, a 15-base ODN targeting the CAG
      repeats encoding the poly-glutamine region of the AR (as750/15) was found to be
      most effective. Treatment of LNCaP cells with as750/15 reduced AR expression to
      approximately 2% within 24 hours compared with mock-treated controls. AR down
      regulation resulted in significant cell growth inhibition, strongly reduced
      secretion of the androgen-regulated prostate-specific antigen, reduction of
      epidermal growth factor receptor expression, and an increase in apoptotic cells.
      Mis-sense and mismatched control ODNs had no or only slight effects. Antisense
      inhibition was also very efficient in LNCaP-abl cells, a subline established
      after long-term androgen ablation of LNCaP cells, resulting in inhibition of AR
      expression and cell proliferation that was similar to that seen for parental
      LNCaP cells. This study shows that inhibition of AR expression by antisense AR
      ODNs may be a promising new approach for treatment of advanced human prostate
      cancer.

PMID- 10917203
TI  - Rabbit cytochrome P450 4B1: A novel prodrug activating gene for pharmacogene
      therapy of hepatocellular carcinoma.
AB  - Gene therapy using vector-mediated transfer of prodrug activating genes is a
      promising treatment approach for malignant tumors. As demonstrated recently, the
      novel prodrug activating gene coding for rabbit cytochrome P450 4B1 (CYP4B1) is
      able to induce tumor cell death at low micromolar concentrations in glioblastoma
      cells after treatment with the prodrug 4-ipomeanol (4-IM) in vitro and in vivo.
      The rabbit CYP4B1 converts this prodrug and other furane analogs and aromatic
      amines, such as 2-aminoanthracene, to highly toxic alkylating metabolites,
      whereas the human isoenzyme exhibits only minimal enzymatic activity. In the
      present study, the cDNA encoding rabbit CYP4B1 was used for pharmacogene therapy
      of hepatocellular carcinoma (HCC). Cell clones derived from the human HCC cell
      lines Hep3B, HuH-7, and HepG2 and stably expressing the chimeric protein CYP4B1
      EGFP (the CYP4B1 coding sequence fused to the enhanced green fluorescent protein
      (EGFP) gene) were selected. HCC clones expressing EGFP served as controls. 4-IM
      rapidly induced tumor cell death in CYP4B1-EGFP-expressing clones at low
      concentrations (a 50% lethal dose of between 0.5 and 2 microg/mL). No signs of
      toxicity were found in control cells expressing EGFP even at high prodrug
      concentrations (20 microg/mL). Cell death occurred by apoptosis and was
      independent of functional p53. A pronounced direct bystander effect was observed
      in Hep3B cells, whereas bystander HepG2 and HuH-7 cells were highly resistant to
      toxic 4-IM metabolites. These results demonstrate that the CYP4B1/4-1M system
      efficiently and rapidly induces cell death in HCC cells, and that a cell line
      specific mechanism may exist that limits the extent of the bystander effect of
      this novel prodrug activating system.

PMID- 10917201
TI  - Targeting and eradicating cancer cells by a prostate-specific vector carrying the
      diphtheria toxin A gene.
AB  - Prostate cancer is the most commonly diagnosed malignancy in American men.
      Developing gene therapy for prostate cancer is important, because there is no
      effective treatment for patients in the advanced stages of this disease. A tissue
      specific promoter to transcriptionally target cancer cells is a promising
      approach for gene therapy of prostate cancer. We previously constructed a
      prostate tissue-specific promoter based on the proximal promoter and the upstream
      regulatory sequence of the prostate-specific antigen gene. In the experiments
      described here, we modified our prostate-specific promoter to drive the A domain
      of the diphtheria toxin gene (DTA) in a plasmid vector. The plasmid vector can be
      efficiently transfected into cell lines, using a liposome-mediated transfection
      method. In the transfected prostate cell line, LNCaP, the DTA gene was actively
      transcribed, and significant inhibition of protein synthesis and cytopathic
      effects was observed. However, no pathogenic effects were apparent in the control
      cell lines. The highly specific and efficient cytopathicity of the DTA gene
      vector is therefore potentially useful for systemic treatment of patients with
      metastatic prostate cancer.

PMID- 10917204
TI  - Combined suicide gene therapy for human colon cancer cells using adenovirus
      mediated transfer of escherichia coli cytosine deaminase gene and Escherichia
      coli uracil phosphoribosyltransferase gene with 5-fluorocytosine.
AB  - The virus-directed enzyme/prodrug system using the Escherichia coli cytosine
      deaminase (CD) gene and 5-fluorocytosine (5-FC) suffers from a sensitivity
      limitation in many tumor cells. The E. coil uracil phosphoribosyltransferase
      (UPRT), which is a pyrimidine salvage enzyme, directly converts 5-fluorouracil (5
      FU) to 5-fluorouridine monophosphate at the first step of its activating pathway.
      To improve the antitumoral effect of the CD/5-FC system, we investigated a
      combined suicide gene transduction therapy for human colon cancer cells using two
      separate adenovirus vectors expressing the E. coli CD and E. coli UPRT genes and
      systemic 5-FC administration (the CD, UPRT/5-FC system). The present study
      demonstrates that the CD, UPRT/5-FC system generates a co-operative effect of CD
      and UPRT, resulting in dramatic increases in both RNA- and DNA-directed active
      forms, including 5-fluorouridine triphosphate incorporated into RNA, 5
      fluorodeoxyuridine monophosphate, and the thymidylate synthase inhibition rate,
      compared with the CD/5-FC system. Furthermore a significant increase in the 5-FC
      sensitivity of colon cancer cells was demonstrated in the CD, UPRT/5-FC system
      compared with the CD/5-FC system in vitro and in vivo. These results suggest that
      the CD, UPRT/5-FC system is a powerful approach in gene therapy for colorectal
      cancer.

PMID- 10917205
TI  - Combinational immunotherapy for established tumors with engineered tumor vaccines
      and adenovirus-mediated gene transfer.
AB  - There are currently extensive studies relating to cancer vaccines using tumor
      cells engineered to express immunogenes and cancer gene therapy using adenovirus
      (AdV)-mediated gene transfer. In this study, a mouse tumor cell line, VKCK, was
      cotransfected with genes coding for tumor necrosis factor-alpha (TNF-alpha) and
      costimulatory B7-1 molecule to enhance immunogenicity. The transfectant cell line
      VKCK-TNF-alpha/B7-1 showed reduced tumorigenicity and tumor regression. Its
      inoculation further induced protective immunity; both CD4+ and CD8+ T cells were
      involved in the induction phase, whereas only CD8+ T cells mediated the effector
      phase. Susceptible mice bearing VKCK tumors developed a T helper type 2-dominant
      response, whereas resistant mice with VKCK-TNF-alpha/B7-1 tumor regression
      developed a T helper type 1-dominant response to VKCK, indicating that the tumor
      regression was related to a shift in the cytokine profile of the host from type 2
      to type 1. Vaccination of VKCK-TNF-alpha/B7-1 cells inhibited tumor formation
      derived from a single dose of 3 x 10(6) VKCK cells and eradicated 3-day tumors
      but not 10-day tumors. AdV-mediated TNF-alpha gene transfer by intratumoral
      injection of AdV-TNF-alpha significantly inhibited tumor growth but failed to
      eradicate any well-established tumors. However, combinational immunotherapy with
      vaccination of VKCK-TNF-alpha/B7-1 cells and AdV-mediated TNF-alpha gene transfer
      not only significantly inhibited tumor growth but also eradicated 10-day VKCK
      tumors in three of eight mice. Therefore, the present study may be useful not
      only in understanding the mechanisms responsible for an efficient antitumoral
      immunity, but also in establishing a more effective immunotherapeutic approach
      for cancer patients.

PMID- 10917206
TI  - Impact of liver P450 reductase suppression on cyclophosphamide activation,
      pharmacokinetics and antitumoral activity in a cytochrome P450-based cancer gene
      therapy model.
AB  - The effect of the antithyroid drug methimazole (MMI) on cytochrome P450/P450
      reductase-dependent activation of the anti-cancer prodrug cyclophosphamide (CPA)
      was investigated in a rat model of P450 prodrug activation-based cancer gene
      therapy. MMI treatment decreased the expression of hepatic P450 reductase by
      approximately 75% but did not alter P450 reductase levels in a 9L gliosarcoma
      growing in vivo as a subcutaneous solid tumor. In a pharmacokinetic study, MMI
      treatment significantly decreased the peak plasma concentration of the active,
      P450-generated metabolite 4-hydroxy-CPA, from 84.1 to 57.8 microM, and
      substantially prolonged its apparent half-life, from 25.4 to 54.3 minutes. The
      area under the plasma concentration x time curve and clearance values for 4
      hydroxy-CPA were largely unchanged, however, indicating that MMI decreases the
      rate but not the overall extent of hepatic CPA activation. MMI alleviated some of
      the systemic toxicities of CPA treatment, as judged by the moderation of CPA
      induced body weight loss and hematuria. The impact of MMI on CPA antitumoral
      activity was evaluated in rats implanted with 9L tumors transduced with P450
      reductase in combination with the CPA-activating P450 2B1, which confers the
      capacity for intratumoral prodrug activation and leads to markedly enhanced
      chemosensitivity. CPA given as a single, subtherapeutic dose of 75 mg/kg resulted
      in a 13.8 day growth delay, whereas CPA in combination with MMI increased the
      growth delay to 17.4 days. By contrast, a tumor growth delay of only 3.4 days was
      observed in animals bearing 9L wild-type tumors given the same drug combination.
      We conclude that the selective reduction of liver P450 reductase after MMI
      treatment decreases the rate of hepatic drug activation and the host toxicity of
      CPA without loss of the antitumoral effect, thus increasing the therapeutic index
      of CPA in a P450-based cancer gene therapy model, where CPA undergoes localized
      drug activation at its intratumoral site of action.

PMID- 10917207
TI  - Transformation-defective adenovirus 5 E1A mutants exhibit antioncogenic
      properties in human BLM melanoma cells.
AB  - Adenoviral E1 A proteins exhibit a strong tumor-suppressive activity in human
      tumor cells. However, E1 A is capable of transforming rodent and human cells in
      cooperation with other oncoproteins, such as activated RAS. Thus, the therapeutic
      use of wild-type E1A harbors the principal risk of enhancing tumor malignancy.
      This prompted us to construct E1A 13S cDNA-derived mutants that were unable to
      transform baby mouse kidney cells in cooperation with E1B and to test their tumor
      suppressive activity in BLM human melanoma cells. Anchorage-independent growth in
      soft agar was reduced for those cell lines expressing the E1AdelCR2 mutant, which
      lacks the entire conserved region 2 (CR2) sequences, or for cells expressing the
      E1AcR3Ex2 mutant, which contains CR3 plus exon 2 sequences. In contrast, cell
      lines expressing the entire E1A wild-type (E1AWT) or only the exon 2 sequences
      (E1AEx2) grew like the parental BLM cells. Moreover, inoculation of nude mice
      with BLM cells or cells expressing E1AEx2 revealed large tumors after 2 weeks. In
      contrast, tumors derived from E1AdelCR2- or E1ACR3Ex2-expressing cells exhibited
      a substantial delay in tumor growth accompanied by a loss of E1A expression in
      the outgrown tumors. Cell lines expressing E1AWT showed an intermediate
      phenotype. Thus, expression of CR3 plus exon 2 sequences is sufficient to enhance
      both the antioncogenic properties and the therapeutic safety of E1A in our
      system.

PMID- 10917208
TI  - Cytotoxicity, apoptosis, and viral replication in tumor cells treated with
      oncolytic ribonucleotide reductase-defective herpes simplex type 1 virus (hrR3)
      combined with ionizing radiation.
AB  - The viral ribonucleotide reductase (rR)-defective herpes simplex type-1 (HSV-1)
      virus (hrR3) has been shown previously to preferentially replicate in and kill
      tumor cells. This selectivity is associated with tumor cell up-regulation of
      mammalian rR. Ionizing radiation (IR) is currently used in the therapy of many
      malignancies, including glioblastoma, cervical carcinoma, and pancreatic
      carcinoma. IR has been shown to up-regulate mammalian rR in tumor cells and
      appears to increase the efficacy of at least one non-rR-deleted HSV-1 strain in
      an in vivo tumor model. Here, we test the hypothesis that a single therapeutic
      radiation fraction will increase the replication and toxicity of hrR3 for
      malignant cell lines in vitro. PANC-1 pancreatic carcinoma, U-87 glioblastoma,
      and CaSki cervical carcinoma cell lines were treated with varying doses of IR and
      subsequently infected with hrR3 or KOS (wild-type HSV-1 strain). Cell survival
      was then measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium
      bromide assay and trypan blue exclusion cytometry. At 72 hours posttreatment,
      irradiation with 2 Gy reduced survival from 100% to 76% in noninfected cells,
      from 61% to 48% in KOS-infected cells, and from 39% to 27% in hrR3-infected PANC
      1 cells. As such, analysis of variance indicated that the toxicity of the two
      modalities was additive. Similar additivity was seen in U-87 MG and CaSki cells.
      Absolute survival of hrR3-infected or KOS-infected PANC-1 cells decreased as a
      function of time after treatment (24-72 hours) and multiplicity of infection
      (MOI) (0.05-5.0). However, the relative decrease in survival with the addition of
      IR to hrR3 or KOS in PANC-1 cells was not markedly affected by altering MOI (0.05
      5.0), time (24-72 hours), radiation dose (2-20 Gy), or cell culture conditions
      (confluent/growth arrested). We used fluorescence-activated cell sorter analysis
      with the cationic lipophilic dye DiOC6 to quantify a reduction in mitochondrial
      membrane potential that'is associated with apoptosis. Fluorescence-activated cell
      sorter analysis indicated increased apoptosis in both hrR3- and IR-treated cells
      at 48-72 hours, with hrR3 alone producing the most induction. Viral yields from
      PANC-1 cells after irradiation and infection were examined. No significant
      differences were seen between irradiated and nonirradiated cells in viral
      replication, with hrR3 producing single-step titers of 3.1 +/- 0.9 x 10(5) and
      4.0 +/- 1.2 x 10(5) plaque-forming units/mL in nonirradiated and irradiated
      cells. Thus, complementary toxicity was seen between IR and hrR3 or KOS,
      regardless of cell type, time, MOI, IR dose, or culture conditions, without
      evidence of augmented apoptosis or viral replication.

PMID- 10917209
TI  - Interleukin-12 (IL-12) gene therapy of leukemia: immune and anti-leukemic effects
      of IL-12-transduced hematopoietic progenitor cells.
AB  - Recombinant interleukin-12 (rlL-12) is a potent immunomodulatory cytokine that
      has been shown to exert strong antitumoral and antimetastatic activity against
      several mouse tumors grown as solid lesions. The therapeutic efficacy of rIL-12
      against hematological tumors and the transfer of IL-12 genes into hematopoietic
      progenitor cells to deliver IL-12 to the bone marrow (BM) to treat residual
      leukemia has not been studied adequately. We have investigated the retroviral
      mediated transduction of hematopoietic progenitor cells with IL-12 genes and the
      in vivo anti-leukemic activity of transduced cells against the murine myeloid
      leukemia cell line 32Dp210. We were able to efficiently transduce the IL-3
      dependent 32Dc13 myeloid progenitor cell line and primary hematopoietic
      progenitor cells using an MFG-based polycistronic retroviral vector containing
      the cDNAs of p35 and p40 murine IL-12 genes. 32Dc13 myeloid progenitor cells
      expressing IL-12 genes (32DIL-12 cells) have stably secreted biologically active
      murine IL-12 for >9 months. Mice transplanted with 32DIL-12 cells transiently
      express the transgene in the BM and spleen, which is associated with a rapid
      elevation of interferon-gamma (IFN-gamma) in the circulation and with secretion
      of IFN-gamma by spleen cells in vitro. In addition, spleen and BM cells of mice
      injected with 32DIL-12 cells readily acquire the capacity to lyse natural killer
      cell-sensitive YAC-1 target cells and 32Dp210 myeloid leukemia cells.
      Furthermore, whereas mice challenged with leukemia cells suffered 100% mortality
      within 14 days, approximately 40% of mice coinjected with 32Dp210 leukemia cells
      and 32DIL-12 progenitor cells exhibited long-term, leukemia-free survival (>60
      days). This study demonstrates that IL-12 can be stably expressed in
      hematopoietic cells; in addition, when transplanted, transduced cells induce IFN
      gamma production and activation of natural killer cells, both of which may be
      involved in inhibiting the progression of leukemia in vivo.

PMID- 10917210
TI  - Biological activity and safety of adenoviral vector-expressed wild-type p53 after
      intratumoral injection in melanoma and breast cancer patients with p53
      overexpressing tumors.
AB  - p53 mutations are common genetic alterations in human cancer. Gene transfer of a
      wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in
      vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of
      a replication-defective adenoviral expression vector containing wt p53 was
      carried out in patients with metastatic melanoma or breast cancer with increased
      p53 protein immunoreactivity in pretreatment tumor biopsies. The biological
      activity of the injected wt p53 was assayed by reverse transcriptase-polymerase
      chain reaction in tumor tissue. A total of six (five melanoma and one breast
      adenocarcinoma) patients were treated at dose levels dependent upon tumor
      size/dose escalation sequence. Five of six patients became positive for the
      transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the
      four patients assayed, all developed anti-adenoviral antibodies. Adverse
      reactions associated with i.t. injection were mild, with no obvious correlation
      between the incidence, severity, or relationship of the events and drug dose. p53
      gene therapy by i.t. injection of a replication-defective adenoviral expression
      vector is safe, feasible, and biologically effective (with respect to
      transduction frequency) in patients with either metastatic melanoma or breast
      cancer.

PMID- 10917211
TI  - A herpesvirus saimiri-based gene therapy vector with potential for use in cancer
      immunotherapy.
AB  - The herpesvirus saimiri (HVS) genome has the capacity to incorporate large
      amounts of heterologous DNA and can be maintained episomally in many different
      human cell types. To evaluate the efficacy of HVS-mediated gene transfer into
      human hemopoietic cells, we investigated the ability of an HVS-based construct,
      carrying the enhanced green fluorescent protein (EGFP) and neomycin resistance
      genes, to transduce a variety of human hemopoietic cell lines and primary CD34+
      cells. As measured by flow cytometry, the numbers of EGFP+ cells at 2 days
      postinfection differed between various cell types ranging, from 1.3% for KG1
      cells to 56.8% for THP-1 cells. In addition, the expression of EGFP in Jurkat
      cells was retained at >95% per round of cell division over a period of 6 weeks
      (comparable with Epstein-Barr virus-derived gene therapy systems). Although the
      virus was not specifically disabled, no lytic viral mRNAs could be detected in
      transduced Jurkat cells, and infectious virus could not be detected by sensitive
      virus recovery assay. We also describe a simple centrifugation method that
      increases the efficiency of transduction by >100% in some cases and may be
      generally applicable to other herpesvirus-based vectors for ex vivo gene
      delivery. Using this technique, we were able to demonstrate a tropism for
      CD34+/CD14+ cells, transducing 30% of the population. These cells are known to
      give rise to dendritic cells (the most potent of the antigen-presenting cells),
      suggesting that the vector could be used to deliver DNA sequences encoding tumor
      antigens for cancer immunotherapy.

PMID- 10917212
TI  - Efficacy of herpes simplex virus thymidine kinase in combination with cytokine
      gene therapy in an experimental metastatic breast cancer model.
AB  - Immunotherapy in combination with suicide gene therapy for breast cancer was
      tested using a metastatic animal model. Subcutaneous injection of the
      nonimmunogenic breast cancer cell line 4T1 in BALB/C mice gave rise to tumors in
      100% of mice with both micrometastases and macrometastases in the lung. We used
      the herpes simplex virus thymidine kinase (HSV-TK) gene along with the cytokine
      genes granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2
      (IL-2) to determine their effect on tumor regression and inhibition of lung
      metastasis. Adenoviral (AV) vectors carrying these transgenes, in separate
      constructs, were used in this study. Intratumoral administration of AV-TK
      followed by 10 days of ganciclovir treatment resulted in a delay in tumor growth
      and, in some cases, in a low to moderate reduction in tumor volume. Inclusion of
      either GM-CSF or IL-2 gene with HSV-TK resulted in a slightly greater reduction
      in tumor volume, although these data were not significantly different from those
      obtained for TK treatment alone. However, when both cytokine genes were combined
      with TK, a substantial reduction in tumor growth was observed compared with HSV
      TK alone (P < .02). Tumor weight data also exhibited superior efficacy of TK/GM
      CSF/IL-2 treatment when compared with animals treated with TK gene only (P <
      .01). More importantly, TK/GM-CSF/IL-2 combination gene therapy induced a
      significant reduction in lung metastasis compared with any other treatment groups
      in the 4T1 model (P < .001 between TK GM-CSF/IL-2 versus TK only). Surgical
      excision of primary tumors after TK/GM-CSF/IL-2 plus ganciclovir treatment
      resulted in anti-metastatic activity that was similar to that observed for
      animals in which no surgery was performed. Survival analysis showed a significant
      difference between animals treated with AV-TK/GM-CSF/IL-2 and animals treated
      with TK only at 35 days after virus injection (P < .01). Immunophenotypic data
      suggest infiltration of lymphocytes within the tumor microenvironment in TK- and
      cytokine gene-treated animals. Thus, the overall data presented here demonstrate
      that TK gene therapy in combination with GM-CSF and IL-2 gene-mediated
      immunotherapy strategies have important implications in the treatment of breast
      cancer.

PMID- 10917213
TI  - A high degree of natural immunologic priming to the capsular polysaccharide may
      not prevent Haemophilus influenzae type b meningitis.
AB  - BACKGROUND: A current debate is whether the immunologic priming of infants with
      Haemophilus influenzae type b (Hib) conjugate vaccines would be protective in the
      absence of circulating antibody to the capsular polysaccharide (PS). Data from
      the prevaccine era on the PS antibody responses of older children to Hib
      meningitis may be informative on this issue. METHODS: PS antibody was assayed by
      radioantigen binding in sera taken in the first month postadmission in 47
      children ages 2 to 136 months with culture-proved Hib meningitis. RESULTS: Sera
      obtained on admission had very low antibody concentrations, and the subsequent
      response during convalescence was age-dependent. The major finding is that some
      patients, including 10 of 11 children older than 2 years, had substantial
      antibody elevations within a few days of admission, increases resembling the
      response to PS vaccine in infants primed with PS-protein conjugate vaccines.
      CONCLUSIONS: In this group of patients with Hib meningitis, natural priming did
      not prevent infection. Hib may have the ability to invade despite the capacity
      for a vigorous antibody response.

PMID- 10917214
TI  - Rehospitalization because of respiratory syncytial virus infection in premature
      infants younger than 33 weeks of gestation: a prospective study. IRIS Study
      Group.
AB  - OBJECTIVE: To collect data on hospitalization for respiratory syncytial virus
      (RSV) infections and presumptive risk factors for rehospitalization among
      premature infants in Spain. DESIGN: Observational, prospective, longitudinal,
      multicenter study. SETTING: Fourteen Spanish neonatal units with an annual birth
      cohort of 57,000 infants. PATIENTS: All children (n = 680) born < or =32 weeks of
      gestational age between April 1, 1998, and March 31, 1999, and discharged from
      the hospital before March 31, 1999, were included in the study. A total of 96
      were excluded because of administration of prophylactic treatment (n = 55) or
      were lost to follow-up (n = 41). Five children died during the study period, but
      death was related to RSV in only 1 case. METHODS AND MAIN OUTCOME MEASURES:
      Neonatal and demographic data were recorded at the initial visit. Infants were
      prospectively followed at monthly intervals up to March 31, 1999. In patients
      rehospitalized for respiratory disorders, further data about RSV status and
      morbidity were collected. A comparison was made between children rehospitalized
      for RSV infection and those who were not. The influence of factors on the
      probability of rehospitalization for RSV infection was assessed by logistic
      regression analysis. RESULTS: Of the 584 evaluable patients 118 (20.2%) were
      rehospitalized for respiratory disease during the study period. The causative
      pathogen was identified in 89 (75.4%) hospital admissions. Of these 59 (66.3%)
      were a result of RSV infection in 53 children; 6 were reinfections. In a logistic
      regression model significant independent prognostic variables included: lower
      risk of RSV hospitalization with increase gestational age [odds ratio (OR), 0.85;
      95% confidence interval (CI), 0.72 to 0.99; P < 0.047]; higher risk with chronic
      lung disease (OR = 3.1; 95% CI 1.22 to 7.91; P < 0.016); and living with school
      age siblings (OR = 1.86; 95% CI 1.01 to 3.4; P < 0.048). CONCLUSION: This large
      descriptive study has enabled us to define the influence of specific risk factors
      that increase the risk of rehospitalization for RSV infection in preterm infants.
      Such studies help to define the appropriate role of available prophylactic
      interventions and establish treatment guidelines.

PMID- 10917215
TI  - Serum procalcitonin, C-reactive protein and interleukin-6 for distinguishing
      bacterial and viral pneumonia in children.
AB  - OBJECTIVE: Serum procalcitonin (PCT), C-reactive protein (CRP) and interleukin-6
      (IL-6) concentrations were measured in 126 children hospitalized for community
      acquired, radiologically confirmed pneumonia to assess whether these host
      response values could be used to distinguish bacterial from viral pneumonia.
      METHODS: The samples for PCT, CRP and IL-6 measurements were obtained on
      admission or the first day of hospitalization. The etiology of pneumonia was
      studied with an extensive panel of methods that detected 6 bacteria and 11
      viruses. RESULTS: In all, 54% had evidence of bacterial pneumonia, and 32% had
      evidence of sole viral pneumonia. In 14% of the cases the etiology could not be
      determined. Children with bacterial pneumonia had significantly higher PCT
      (median 2.09 ng/ml vs. 0.56 ng/ml, P = 0.019) and CRP concentrations (96 mg/l vs.
      54 mg/l, P = 0.008) than those with sole viral etiology. However, the values
      markedly overlapped. No significant difference in IL-6 concentrations was seen
      between the two patient groups. Using PCT > or = 2.0 ng/ml, CRP > or = 150 mg/l
      or IL-6 > or = 40 pg/ml, the specificity was > or =80% for bacterial pneumonia.
      The sensitivities with these cutoff values were 50% for PCT, 31% for CRP and 34%
      for IL-6. CONCLUSIONS: The results indicate that the measurement of serum PCT,
      CRP and IL-6 has little value in the differentiation of bacterial and viral
      pneumonia in children. However, in some patients with very high serum PCT, CRP or
      IL-6 values, bacterial pneumonia is probable.

PMID- 10917216
TI  - Pneumocystis carinii pneumonia in South African children infected with human
      immunodeficiency virus.
AB  - BACKGROUND: Pneumocystis carinii pneumonia (PCP) has been regarded as uncommon in
      HIV-infected patients in Africa, but diagnostic difficulties and geographic
      variability may partly account for this. There is little information on the
      incidence of PCP in HIV-infected children in Africa. AIM: To investigate (1) the
      incidence and associated features of PCP in African HIV-infected children and (2)
      the usefulness of sputum induction and nasopharyngeal aspirates (NPAs) for
      diagnosis of PCP. METHODS: HIV-infected children hospitalized with pneumonia were
      prospectively enrolled in a 1-year study in South Africa. History, examination,
      chest radiology and blood tests (including HIV testing) were performed. Sputum
      induction (5% NaCl nebulization) or nondirected bronchoalveolar lavage in
      intubated patients was performed for P. carinii identification using
      immunofluorescence and silver stain; immunofluorescence was also done on
      nasopharyngeal aspirates (NPAs). RESULTS: Of 151 HIV-infected children [47%
      female; median age, 9 (range, 3 to 23) months], 87 had been previously diagnosed
      with HIV whereas 64 (42.4%) were found to be HIV-positive at the time of
      admission. PCP occurred in 15 children (9.9%; 95% confidence interval, 5.9 to
      15.5) and was the AIDS-defining infection in 13 of 64 (20.3%; 95% confidence
      interval, 11.8 to 31.5). Only 1 of 59 children receiving prophylaxis (1.7%)
      developed PCP compared with 14 of 92 (15.2%) not taking prophylaxis [relative
      risk, 0.11 (0.02 to 0.82), P = 0.007]. PCP-infected children were younger [3
      (range, 3 to 4) vs. 10 (range, 4 to 24) months, P < 0.001] and presented with
      more severe pulmonary disease as indicated by a higher respiratory rate [63
      (range, 60 to 73) vs. 50, (range, 40 to 60) P < 0.001], heart rate [160 (range,
      136-180) vs. 140 (range, 120-152) P = 0.025] and a greater incidence of cyanosis
      (53% vs. 26%, P = 0.025). Clinical signs of HIV infection, occurring in 96% of
      children, were equally prevalent in both groups. High serum lactate dehydrogenase
      was the only laboratory investigation that distinguished PCP-infected from
      uninfected children [626 (range, 450 to 1098) vs. 307 (range, 243 to 465)
      units/l], P < 0.001. No radiologic features were found to be diagnostic of PCP.
      P. carinii was identified in 9 sputa and 6 bronchoalveolar lavage specimens, but
      all corresponding NPAs were negative. Seven of 15 (47%) children with PCP died
      while hospitalized compared with 24 of 136 (18%) without PCP [relative risk, 1.21
      (range, 0.99 to 1.47), P = 0.008]. CONCLUSION: PCP is an important pathogen in
      HIV-infected infants in South Africa and is associated with a high mortality.
      Induced sputum is effective for obtaining lower respiratory tract secretions for
      diagnosis of PCP but an NPA is not useful.

PMID- 10917217
TI  - Colonization by Streptococcus penumoniae in human immunodeficiency virus-infected
      children.
AB  - OBJECTIVE: Children with HIV infection are particularly susceptible to invasive
      pneumococcal disease, yet the effect of HIV infection and its medical management
      on colonization and resistance to antibiotics are poorly described. To provide a
      basis for medical practice, we determined the prevalence of nasopharyngeal
      colonization and antibiotic resistance of Streptococcus pneumoniae in children
      with HIV infection. METHODS: Cross-sectional prevalence sample of children
      attending the pediatric HIV and pulmonary clinics to examine nasopharyngeal
      colonization with S. pneumoniae and antibiotic resistance to beta-lactams and
      trimethoprim-sulfamethoxazole (T/S). Subjects were matched by age and date of
      clinic visit. RESULTS: The colonization rate with S. pneumoniae of HIV-infected
      and -indeterminate children was equal to that of controls (20% vs. 19%). HIV
      infection, CDC staging or receipt of oral antibiotic therapy did not affect
      colonization. Isolates from HIV-infected and -indeterminate children were less
      likely to be penicillin-resistant than those from controls (18% vs. 50%). There
      was no difference in pneumococcal resistance to T/S among isolates from subjects
      and controls, despite 72% T/S use in the HIV clinic. CONCLUSION: Colonization
      with S. pneumoniae in HIV disease is no different from that of comparable
      children. The high incidence of pneumococcal disease and prophylaxis with T/S are
      not related to nasopharyngeal colonization. Antibiotic prophylaxis of HIV
      infected children does not necessarily lead to increased resistance of S.
      pneumoniae.

PMID- 10917219
TI  - Prospective cohort study of children born to human immunodeficiency virus
      infected mothers, 1985 through 1997: trends in the risk of vertical transmission,
      mortality and acquired immunodeficiency syndrome indicator diseases in the era
      before highly active antiretroviral therapy.
AB  - OBJECTIVES: To assess changes in the risk of vertical transmission of HIV and
      changes in both mortality and morbidity among children in southern Connecticut
      with HIV infection after the introduction of treatment of HIV-infected pregnant
      women with antiretroviral drugs and of regimens to prevent or to treat AIDS
      indicator diseases in infected children. METHODS: The risk of vertical
      transmission of HIV, the rates of death and of AIDS indicator diseases and
      temporal trends in each were determined for children born in the first 5 years of
      a prospective, longitudinal cohort study (Period 1: December 1, 1985, through
      November 30, 1990) compared with those for children born during the latter 7
      years of the study (Period 2: December 1, 1990, through November 30, 1997).
      RESULTS: Of 347 infants enrolled, HIV infection status could be determined for
      341; 44 (12.9%) were infected. The risk of vertical transmission declined from
      20.7% among children born in Period 1 to 6.5% among children born in period 2
      (rate ratio, 3.2; 95% confidence interval, 1.7 to 6.0; P = 0.0001). Of the 21
      infected children who died, 11(52%) were < or =18 months of age and 18 (86%) were
      < or =36 months of age at the times of death. Approximately one-fourth of
      infected children born during each period died at < or =18 months of age. Among
      those < or =36 months of age, 15 deaths occurred during 878 person months of
      observation for those born in Period 1 compared with 3 deaths that occurred
      during 334 person months for those born in Period 2 (rate ratio, 1.9; 95%
      confidence interval, 0.5 to 10.3; P = 0.45). Of the 44 children infected with
      HIV, 32 had one or more AIDS indicator diseases (a total of 67 episodes), 73% of
      which occurred when the children were < or =36 months of age. Among children born
      in Period 2, none developed Pneumocystis carinii pneumonia and the rates of
      Mycobacterium avium complex disease and of wasting syndrome declined, but the
      differences in rates of disease were not statistically significant. CONCLUSION: A
      substantial and statistically significant decline in the risk of vertical
      transmission of HIV-1 occurred during the 12-year study period. In contrast
      although there was a trend toward a decrease in mortality among HIV-infected
      children < or =36 months of age and changes in the overall rates of AIDS
      indicator diseases among children born in Period 1 compared with Period 2, the
      differences were not statistically significant.

PMID- 10917218
TI  - Pneumococcal and influenza immunization and human immunodeficiency virus load in
      children.
AB  - OBJECTIVE: HIV-infected children receiving influenza vaccine, pneumococcal
      vaccine and both vaccines concurrently were studied to examine the effect of
      immunization on plasma HIV viral load. METHODS: Thirteen children received
      immunizations: pneumococcal vaccine, 5; pneumococcal and influenza vaccines, 7;
      and influenza vaccine, 1. Most patients (12 of 13) were receiving combination
      reverse transcriptase inhibitor antiretroviral therapy without protease
      inhibitors at the time of immunization. Baseline plasma HIV RNA was determined 1
      month prior (11 of 13), 2 weeks prior (12 of 13) and on the day of immunization
      (12 of 13). Plasma HIV RNA was assayed at 2 weeks (11 of 13), 4 weeks (12 of 13)
      and 3 months (5 of 13) after immunization. T cell activation markers (HLA-DR+,
      CD38+ and CD45RO+, CD28+) were examined for both CD4+ and CD8+ lymphocytes on the
      day of immunization and 2 weeks after immunization for 11 children. RESULTS: Only
      one child developed a >0.5-log increase in viral load at any time after
      immunization. There was no correlation between an increase in viral load and
      antibody response to pneumococcal vaccine. At least one activation marker
      increased (> 10%) for two children receiving pneumococcal vaccine and two
      children receiving pneumococcal and influenza vaccines. One of these children
      experienced an increase in viral load. CONCLUSION: Immunization with pneumococcal
      and influenza vaccines, alone or in combination, is rarely associated with a
      significant increase in HIV plasma RNA in children receiving combination
      antiretroviral therapy.

PMID- 10917220
TI  - Mycobacterium tuberculosis infection in pediatric liver transplant recipients.
AB  - OBJECTIVES: To study the incidence, clinical presentation, management,
      complications and outcome of tuberculosis in pediatric liver transplant
      recipients. METHODS: A retrospective review of the medical records of children
      who underwent liver transplantation between 1991 and 1998. RESULTS: Mycobacterium
      tuberculosis infection occurred in 6 of 254 (2.4%) children undergoing liver
      transplantation between 1991 and 1998. Cough, pyrexia and poor appetite were
      common presentations; one-half had normal chest radiographs. The median time to
      confirmation of diagnosis was 8 months (range, 1 to 17 months). Tests
      contributing to diagnosis included: Ziehl-Neelsen (ZN) stain (2 patients), M.
      tuberculosis polymerase chain reaction (1 patient), Mantoux test (1 patient) and
      histopathology (4 patients). Family health screening was productive for 4
      patients. Duration of treatment varied from 9 to 18 months. Isoniazid-induced
      hepatitis was observed in 2 patients but resolved with dose reduction. Two
      patients died while receiving treatment, one of Klebsiella spp. septicemia and
      the other of pulmonary hemorrhage. CONCLUSIONS: Tuberculosis after liver
      transplantation has a significant morbidity and mortality. Pretransplantation a
      personal and family history of tuberculosis must be sought, and screening of
      patients and their families should be considered. Standard regimens incorporating
      isoniazid and rifampin are effective, but regular monitoring of liver function is
      essential to detect drug-induced hepatotoxicity.

PMID- 10917221
TI  - Bacteremic urinary tract infection in children.
AB  - OBJECTIVE: To assess the clinical characteristics of bacteremic urinary tract
      infection (UTI) in children. DESIGN: Clinical data of Finnish children with
      bacteremic UTI (n = 134) from 1985 to 1994 were analyzed. Their symptoms,
      laboratory and imaging findings were compared with those of age- and sex-matched
      patients hospitalized for blood culture negative UTI. RESULTS: Generally, no
      major differences were seen in clinical findings between bacteremic and
      nonbacteremic patients. Bacteremic children had more frequent feeding problems (P
      = 0.02), and children > or =12 months of age tended more often to have abdominal
      pain and vomiting than did nonbacteremic patients. Fever was the major initial
      symptom in both study groups, but no significant difference occurred in the mean
      highest temperature or in the mean of duration of fever before admission to the
      hospital. The mean concentration of serum C-reactive protein on admission was
      significantly higher in bacteremic patients (116 vs. 76 mg/l; P < 0.01). After
      onset of antimicrobial treatment fever lasted significantly longer in bacteremic
      patients than in control patients (means, 2.3 vs. 1.1 days; P < 0.01). Anatomic
      or functional abnormalities in the urinary tract were detected in 51% vs. 46%,
      respectively. Obstruction of the urinary tract (9% vs. 1%, P < 0.01) and Grade 3
      to 5 vesicoureteral reflux (30% vs. 16%, P = 0.02) were significantly more
      frequent in bacteremic patients with UTI. Obstruction or vesicoureteral reflux
      was found in 46% of children with bacteremic UTI caused by Escherichia coli vs.
      89% of children with non-E. coli infection (P < 0.01). CONCLUSIONS: Clinical
      symptoms do not significantly distinguish bacteremic from nonbacteremic children
      with UTI. Outcome of bacteremic UTI was comparable with that of nonbacteremic
      UTI. Bacteremic children, especially those with non-E. coli UTI, more often had
      anatomical or functional abnormalities in the urinary tract.

PMID- 10917222
TI  - Placental transfer and decay of maternally acquired antimeasles antibodies in
      Nigerian children.
AB  - BACKGROUND: In developing countries vaccination against measles virus (MV) is
      generally administered at 9 months of age, although it is well-documented that
      protection of most infants by passively acquired maternal MV antibodies is waning
      before immunization is given. The purpose of this study was to investigate the
      decay of maternally derived MV antibodies in Nigerian infants as well as to
      compare a German and Nigerian cohort of paired mothers and newborns regarding the
      placental transfer efficiency of MV-specific IgG and total IgG antibodies.
      METHODS: MV-specific IgG antibodies were measured with a commercially available
      MV-enzyme-linked immunosorbent assay, a recombinant hemagglutinin enzyme-linked
      immunosorbent assay as well as a neutralization assay. Total IgG values were
      determined with a standard immunoturbidimetric test. RESULTS: Anti-MV IgG titers
      were twice as high in German newborns as in Nigerian newborns. An increased
      concentration of immunoglobulins transferred via the placenta was found only in
      the German cohort. High concentrations of total maternal IgG reduced the
      concentration of MV-specific as well as total IgG that crossed the placenta.
      Furthermore only 17% of the 4-month-old Nigerian infants were still protected
      against measles. Antibodies had a biologic half-life of 33 days and a biochemical
      half-life of 48 days. CONCLUSIONS: Our findings demonstrate that the decay of
      passively acquired MV antibodies occurred even more rapidly than expected
      resulting in susceptibility to MV in most of the 4-month-old infants in Nigeria.
      Furthermore transfer of maternal anti-MV IgG and total IgG antibodies to the
      newborn was more efficient in the German cohort compared with the Nigerian group.
      These findings suggest the use of alternative vaccination strategies in
      developing countries to possibly reduce the window of susceptibility against
      measles.

PMID- 10917224
TI  - Role of varicella-zoster virus in stroke syndromes.

PMID- 10917223
TI  - Leukocytosis in children with Escherichia coli O157:H7 enteritis developing the
      hemolytic-uremic syndrome.
AB  - BACKGROUND: Fewer than 10% of children with Escherichia coli O157:H7 enteritis
      develop hemolytic-uremic syndrome (HUS). OBJECTIVE: To determine whether
      circulating leukocytes are independent risk markers of developing HUS during E.
      coli O157:H7 enteritis. METHODS: We reviewed the charts of all children with
      culture-proved E. coli O157:H7 infections seen at Sainte-Justine Hospital between
      1987 and 1997. Epidemiologic data, laboratory indices and circulating leukocytes
      counts were noted. HUS diagnosis was validated with independent HUS patient lists
      from the pediatric nephrology services of tertiary care hospitals in the Montreal
      metropolitan area. The date of onset of enteritis was determined by two
      independent observers. Leukocyte counts were compared among the following
      independent groups: (1) uncomplicated O157:H7 enteritis (Group 1); (2) O157:H7
      enteritis with the subsequent development of HUS (Group 2); (3) HUS already
      present at the time of medical consultation (Group 3). RESULTS: There were 369
      children with E. coli O157:H7 infection. A complete blood count was not performed
      in 114 (31%) patients. Observers disagreed on the date of onset of
      gastroenteritis in 34 (9%) children only (kappa 0.92). The study population thus
      included 221 patients: Group 1, n = 161; Group 2, n = 27; and Group 3, n = 33.
      Patients developing HUS (Group 2) presented greater total leukocyte (P < 0.008),
      polymorphonuclear (P < 0.008) and monocyte (P < 0.07) counts than those with an
      uncomplicated course (Group 1). Logistic regression analysis showed that young
      age [odds ratio (OR), 0.98; 95% confidence interval (CI), 0.96 to 0.99], duration
      of enteric prodrome < or =3 days (OR 4.8, 95% CI 1.13 to 20.7) and initial
      leukocytosis (OR 1.22, 95% CI, 1.11 to 1.35) were independent predictors of HUS.
      CONCLUSIONS: Based on the variables identified above, further studies are needed
      to determine whether the inflammatory response of the host represents only a
      marker of the severity of gastrointestinal infection or whether, alternatively,
      it is a pathophysiologic factor that leads to HUS.

PMID- 10917225
TI  - Fatal varicella-zoster virus antigen-positive giant cell arteritis of the central
      nervous system.

PMID- 10917226
TI  - Evidence-based pediatric infectious diseases.

PMID- 10917227
TI  - Mebendazole and albendazole treatment of geohelminth infections in children and
      pregnant women.

PMID- 10917228
TI  - Newborn with vesicular rash. Tinea corporis (tinea faciei).

PMID- 10917229
TI  - Central nervous system nocardiosis in an immunocompetent child.

PMID- 10917230
TI  - Mediastinal aspergilloma ten years after thoracic surgery.

PMID- 10917231
TI  - Drug-resistant Streptococcus pneumoniae spinal epidural abscess in a toddler.

PMID- 10917232
TI  - Detection of Mycoplasma pneumoniae by polymerase chain reaction in middle ear
      fluids from infants with acute otitis media.

PMID- 10917233
TI  - Enterococcal meningitis in an infant complicating congenital cutis aplasia.

PMID- 10917234
TI  - Mumps associated with immunoglobulin A nephropathy.

PMID- 10917235
TI  - Gonococcal hand abscess.

PMID- 10917236
TI  - Apparent false positive detection of group a Streptococcus antigen resulting from
      pharyngeal infection with a nonhemolytic Streptococcus pyogenes.

PMID- 10917237
TI  - Management of nontuberculous mycobacterial cervical adenitis.

PMID- 10917238
TI  - Antimicrobial-resistant enterococcal isolates from fluoroquinolone-naive
      children.

PMID- 10917239
TI  - Radiologic case study. Triplane fracture of the distal tibia.

PMID- 10917240
TI  - Legal, medical, and ethical implications of informed consent.

PMID- 10917241
TI  - Lateral femoral split: an alternative for uncemented femoral stem revision
      surgery.

PMID- 10917242
TI  - The effect of intramedullary bone plug on femoral stem migration of
      hydroxyapatite-coated hip arthroplasty.
AB  - This study investigated the effect of intramedullary corticocancellous bone plug
      on the fixation and stability of hydroxyapatite-coated femoral stems in total hip
      arthroplasty (THA). Intramedullary corticocancellous bone plug was used in 30
      patients with hydroxyapatite-coated femoral stems (group A) and a consecutive
      series of 30 patients with hypdroxyapatite-coated stems without bone plug served
      as the control group (group B). Patients underwent clinical and radiographic
      follow-up for at least 2 years. The addition of corticocancellous bone plug to
      the hydroxyapatite-coated stem significantly improved clinical and radiographic
      results. The mean Harris Hip Score at 3 and 6 months postoperatively was 92 and
      94 in group A, and 84 and 87 points in group B (P<.004 and P<.001, respectively).
      There was no significant difference between groups at 1 year postoperatively and
      thereafter. The predominant cause for the difference was the thigh pain score,
      which was reduced at both 3 and 6 months in group A compared to group B (P<.01
      and P<.05, respectively). There also were statistical differences between the two
      groups regarding radiographic signs. The evidence of endosteal bone formation in
      group A patients was superior at 3 and 6 months (P<.001 and P<.01, respectively).
      The appearance of a radiolucent line was significant in group B patients at 3 and
      6 months (P<.001). Femoral stem migration of 3 mm was noted in three group B
      patients versus no group A patients (P<.05). These short-term clinical and
      radiographic results suggest corticocancellous bone plug can provide early pain
      relief and durable implant fixation, but long-term follow-up should be
      considered.

PMID- 10917243
TI  - Operative treatment for Maisonneuve fracture of the proximal fibula.
AB  - This study reviewed operative treatment of Maisonneuve fracture of the fibula in
      26 patients. Operative treatment consisted of restoration of the fibular length,
      repair of the lateral and medial ankle ligamentous structures, and placement of
      one or two suprasyndesmotic screws. After average follow-up of 6.4 years, the
      clinical results were satisfactory in 23 (88.4%) patients. Operative treatment is
      the treatment of choice for Maisonneuve fractures, and a satisfactory outcome may
      be anticipated after appropriate management of any associated bony and
      syndesmotic injuries.

PMID- 10917244
TI  - Adhesive capsulitis of the shoulder in male cardiac surgery patients.
AB  - Two hundred fourteen consecutive male cardiac surgery patients were
      retrospectively evaluated for the incidence of adhesive capsulitis of the
      shoulder and were assessed for risk factors. Only male patients were included, as
      the study took place at a Veteran's hospital. Patients who had no shoulder
      problems prior to cardiac surgery and were experiencing shoulder pain or
      stiffness postoperatively underwent history, physical examination, and
      radiographic studies. Thirty-five patients who had shoulder complaints were
      identified and evaluated. A 3.3% incidence (seven patients) of adhesive
      capsulitis of the shoulder in a male post-cardiac surgery population was
      established.

PMID- 10917245
TI  - Influence of facet joint angles and asymmetric disk collapse on degenerative
      olisthesis of the cervical spine.
AB  - This study examined the facet angles of the joint facets of the intervertebral
      joints, the anterior and posterior heights of the intervertebral disks, and
      cervical lordosis as possible parameters of olisthesis. Lateral radiographs of
      the cervical spine in 123 patients were examined, and parameters were correlated
      to anterolisthesis and retrolisthesis in each segment. Results indicate
      anterolisthesis is caused by a decrease of the facet angles of the caudal joint
      facets. This process is favored by loss of anterior height of the intervertebral
      disks and a flattened position of the cervical spine. Loss of posterior height of
      the intervertebral disks promotes retrolisthesis.

PMID- 10917246
TI  - Compliant prestress fixation in tumor prostheses: interface retrieval data.
AB  - This article reports the first available human retrieval data following the use
      of a new fixation system for tumor prostheses. The compliant prestress (CPS)
      fixation system obviates the need for long intramedullary stems. The CPS was
      designed to provide a stable, high-pressure, motion-free bone-implant interface
      that would prevent aseptic loosening and allow osseointegration at the bone
      implant interface. At 10 months, the fourth patient in the human trial required
      amputation. Backscatter electron microscopy revealed a buttress of new bone had
      formed along 70% of the bone-metal interface, with excellent bony ingrowth
      (average: 42%) into the transverse, porous-coated titanium interface.

PMID- 10917247
TI  - Assessment of femoral neck nonunion with multiplanar computed tomography
      reconstruction.
AB  - Femoral neck fracture nonunion after implant fixation is usually evaluated by
      physical findings and serial radiography. Radiography in hip fixation is
      complicated by inherent anatomy and the geometry of screw placement. Computed
      tomography with multiplanar reconstruction offers adjunct evaluation using
      nonstandard imaging planes tailored to favor fracture plane projection and
      individual screw evaluation. Metal artifacts can be minimized and lack of
      fracture bridging can be excluded with confidence. Experience with seven cases of
      femoral neck fracture nonunion is presented along with image examples.

PMID- 10917248
TI  - Occipital screws in occipitocervical fusion and their relation to the venous
      sinuses: an anatomic and radiographic study.
AB  - This study examined the safe zone for placement of occipital screws without
      endangering the sinuses. In the first part of the study, 10 cadaveric skulls were
      exposed. The borders of the confluences and the transverse sinuses were located
      on the outer table of the occiput. In the second part of the study, six cadaveric
      skulls were used and screws were placed in different sites and angiography of the
      venous sinuses was performed. The exact location of the venous sinuses on the
      outer table of the occiput were analyzed. The examination of the relationship
      between occipital screws placed at different sites and the venous sinuses clearly
      demonstrated that whenever the screws were inserted at the level of the external
      occipital protuberance, or 1 cm below it, sinus injury could rarely be avoided.
      To enhance the safety of the occipitocervical fusion, the external occipital
      protuberance should be avoided, and occipital screws should be placed at least 2
      cm below the superior nuchal line.

PMID- 10917250
TI  - Atypical osteochondroma of the distal femur.

PMID- 10917249
TI  - Use of a closing wedge osteotomy to correct malunion of dorsally displaced extra
      articular distal radius fractures.

PMID- 10917251
TI  - Salmonella osteomyelitis of the hand in an infant with sickle cell disease.

PMID- 10917252
TI  - Bilateral Pipkin type II fractures of the femoral head.

PMID- 10917253
TI  - Villonodular synovitis of the shoulder.

PMID- 10917254
TI  - Electrical stimulation in lumbar spinal fusion.

PMID- 10917255
TI  - The National Prosthetic Patient Database: a national information resource for
      prosthetic prescriptions written in the VA.

PMID- 10917256
TI  - Wheelchairs and related technology for the millennium.

PMID- 10917257
TI  - Quantitative analysis of the effects of audio biofeedback on weight-bearing
      characteristics of persons with transtibial amputation during early prosthetic
      ambulation.
AB  - Residual limb recovery after a transtibial amputation depends largely on close
      monitoring of the weight-bearing activities during the early postoperative stage.
      Although a biofeedback device, in particular audio biofeedback, was recommended
      to be used, no quantitative studies regarding its effectiveness in monitoring the
      weight-bearing activity of a person with amputation were available. In this
      study, six persons with transtibial amputation were asked to replicate a
      prescribed amount of weight bearing using a bathroom scale method during their
      early postoperative ambulatory training. Their weight-bearing characteristics
      with and without using audio biofeedback were continuously monitored using a load
      monitoring device and compared with the prescribed load. The results showed that
      the residual limb would be overloaded using the conventional bathroom scale
      method during early postoperative ambulatory training if no audio biofeedback was
      provided. It was demonstrated that audio biofeedback was useful in preventing the
      residual limb from being overloaded beyond the prescribed load particularly when
      the prescribed load was low.

PMID- 10917258
TI  - Force-directed design of a voluntary closing hand prosthesis.
AB  - This paper presents the design of a body-powered voluntary closing prosthetic
      hand. It is argued that the movement of the fingers before establishing a grip is
      much less relevant for good control of the object held than the distribution of
      forces once the object has been contacted. Based on this notion, the
      configurations of forces on the fingers and the force transmission through the
      whole mechanism were taken as a point of departure for the design, rather than
      movement characteristics. For a good distribution of pinching forces on the
      object and a natural behavior, the prosthesis is made adaptive and flexible. To
      achieve good force feedback, the disturbing influences of the cosmetic glove are
      strongly reduced by a compensation mechanism. To further improve the transmission
      of forces, friction is reduced by furnishing the whole mechanism with rolling
      links. This force-directed design approach has led to a simple mechanism with low
      operating force and good feedback of the pinching force.

PMID- 10917259
TI  - Design enhancement of a solid ankle-foot orthosis: real-time contact pressures
      evaluation.
AB  - The purpose of our study was to evaluate all contact pressures between the molded
      ankle-foot orthosis (MAFO) and the subject during activities of daily living. The
      MAFOs studied are used clinically to reduce plantar contact pressures associated
      with foot ulcers in adult neuropathic diabetic subjects, alleviating abnormal
      pressures by redistributing them to low-pressure plantar regions. While
      effective, MAFOs are often not used by the subject due to weight and comfort
      issues. An understanding of the contact pressures between the subject and the
      orthosis is a first step in improving basic MAFO design. Four nonimpaired, young
      adult males were tested in this study. A right-side MAFO was custom-molded and
      fitted for each subject by the same orthotist. Real-time pressures were obtained
      for the entire contact area using the F-Scan pressure measurement system. The
      data obtained demonstrated high contact pressures along the metatarsals of the
      foot, around the heel and ankle, and adjacent to the strap attachment sites. No
      contact pressures were noted along the posterior calf region during any of the
      activities performed. These data suggest the calf region would be a suitable site
      for material removal for weight reduction and increased comfort, especially in
      warm weather. In addition, these data may be useful to orthotists in improving
      the basic design and to researchers as a starting point for performing complex
      finite element analysis on the MAFO.

PMID- 10917260
TI  - Influence of trunk flexion on biomechanics of wheelchair propulsion.

PMID- 10917261
TI  - Displacement between the seating surface and hybrid test dummy during transitions
      with a variable configuration wheelchair: a technical note.
AB  - Changing seating posture can extend the amount of time a person can safely remain
      seated without damaging tissue or becoming fatigued. The Excelsior is an
      electrically powered wheelchair that utilizes sit-to-stand (STS) and sit-to
      recline (STR) motions to aid in pressure relief. The motion of the wheelchair
      seating system must closely follow anatomical paths or ulcers may develop from
      the resulting shear forces. Displacement between the person and the wheelchair
      seating surface is one measure of these shear forces. The displacement between a
      Hybrid II 50th percentile anthropometric test dummy (ATD) and the seating surface
      of the Excelsior wheelchair was examined during STS and STR with two cushions, a
      Jay Active and a low-profile Roho cushion. The difference between the backrest
      and ATD back angles were 4.29 degrees +/- 2.13 degrees and 1.78 degrees +/- 1.73
      degrees for the Roho and Jay cushions respectively during STS and 3.32 degrees +/
      4.21 degrees and 10.71 degrees +/- 6.20 degrees during STR. These were
      statistically significant at p<.05. During STS, shear displacement between the
      Hybrid II back and Excelsior backrest did not exceed 1.5 cm for either cushion.
      ATD thigh-to-seat displacements were 2.5 cm for the Jay and 3.0 cm for the Roho
      cushion. STR produced dummy thigh-to-seat displacements of 1.5 cm and 3.5 cm for
      the Jay and Roho cushions respectively. Shear displacement in the ATD back was
      about 3.5 cm for the Roho and 6 cm for the Jay. The latter displacement should be
      reduced; however, the other conditions are marginal or acceptable. Hysteresis was
      acceptable or better for all cushion/motion combinations, with the highest net
      displacement of about 2.5 cm.

PMID- 10917262
TI  - Wheelchair caster shimmy II: damping.
AB  - The theory of shimmy damping is investigated including tire friction, spindle
      bearing friction, and hydraulic damping. A new theoretical improvement in
      hydraulic damping is presented. Experimental results are presented along with a
      discussion concerning the limitations due to the approximations used in the
      theory. The basic theory of wheelchair caster shimmy was published by the authors
      in 1984, and an examination of the sources of shimmy damping is corrected and
      updated in this paper.

PMID- 10917263
TI  - Comparative biomechanical evaluation of different wheelchair seat cushions.
AB  - The aim of the present study was to perform a comparative biomechanical analysis
      of four antidecubitus wheelchair cushions. Thirty wheelchair users were
      considered divided into three groups: paraplegic subjects (with no cutaneous
      sensation), neurologic subjects (with intact cutaneous sensation), and elderly
      subjects. The biomechanical evaluation was performed using a piezoresistive
      sensor matrix system to quantify parameters referred to pressure distribution,
      seating surface and posture. Dedicated software was developed for the automatic
      elaboration of the raw data and the computation of the parameters of interest.
      Differences among cushion types and subject groups were analyzed. An analysis of
      time-transient behaviors was also performed. Results showed that no significant
      differences in pressure peak reduction were found among the four cushions.
      Moreover, no time-transient behavior was shown by any cushions. However, both the
      location of pressure peaks and posture were dependent on cushion types.
      Comparison of the three subject groups showed that elderly subjects had the
      highest mean pressure and the lowest contact surface, while paraplegics presented
      the highest pressure peaks. This procedure appears indicated for individualizing
      the prescription of a wheelchair cushion and even for customizing a cushion to
      induce a specific posture.

PMID- 10917265
TI  - Spectral analysis of surface electromyography (EMG) of upper esophageal sphincter
      opening muscles during head lift exercise.
AB  - Although recent studies have shown enhancement of deglutitive upper esophageal
      sphincter opening in healthy elderly patients performing an isometric/isotonic
      head lift exercise (HLE), the muscle groups affected by this process are not
      known. A shift in the spectral analysis of surface EMG activity seen with muscle
      fatigue can be used to identify muscles affected by an exercise. The objective of
      this study was to use spectral analysis to evaluate surface EMG activities in the
      suprahyoid (SHM), infrahyoid (IHM), and sternocleidomastoid (SCM) muscle groups
      during the HLE. Surface EMG signals were recorded continuously on a TECA Premiere
      II during two phases of the HLE protocol in eleven control subjects. In the first
      phase of the protocol, surface EMG signals were recorded simultaneously from the
      three muscle groups for a period of 20 s. In the second phase, a 60 s recording
      was obtained for each of three successive trials with individual muscle groups.
      The mean frequency (MNF), median frequency (MDF), root mean square (RMS), and
      average rectified value (ARV) were used as spectral variables to assess the
      fatigue of the three muscle groups during the exercise. Least squares regression
      lines were fitted to each variable data set. Our findings suggest that during the
      HLE the SHM, IHM, and SCM muscle groups all show signs of fatigue; however, the
      SCM muscle group fatigued faster than the SHM and IHM muscle groups. Because of
      its higher fatigue rate, the SCM muscle group may play a limiting role in the
      HLE.

PMID- 10917264
TI  - Evaluation of the new flexible contour backrest for wheelchairs.
AB  - A new flexible contour backrest for wheelchairs was designed with the objectives
      of offering adequate posture, uniform pressure distribution, and comfort to the
      users while keeping the advantages of conventional sling backrests, such as easy
      to fold, light weight, unobtrusive, and airy. The purpose of this study is to
      compare the new backrest with two commercially available wheelchair backrests, an
      adjustable-tension (AT) backrest and a back cushion on a rigid support (RS), in
      terms of pressure distribution, back profile accommodation, and short-term
      comfort. Evaluations were done with 15 nonimpaired subjects in a static position.
      It was shown that the new backrest distributes pressure in a more uniform way
      than the AT and in a way similar to the RS, while giving a better fit to
      subjects' trunks than other backrests because of its multiple adjustments.
      Finally, subjects felt that the new backrest is as comfortable as the RS and more
      comfortable than the AT.

PMID- 10917266
TI  - Lifting characteristics of functionally limited elders.
AB  - BACKGROUND: The purpose of this study was to investigate the lifting
      characteristics of elders with functional limitations using burden lifting
      smoothness, trunk angular momentum, and back and hip torque, and to correlate
      these characteristics with strength and functional measures. METHODS: Thirty
      elders (65-89 years old) consented to biomechanical analysis of lifting, gait,
      and chair rise, and to maximum isometric strength testing of the hip and knee
      extensors and shoulder flexors. Jerk, the rate of change of acceleration, is a
      measure of smoothness of motion. We calculated peak vertical jerk of the box at
      the beginning part of the lift. Momentum is the product of mass and velocity. HAT
      (head, arms, trunk) angular momentum was calculated during chair rise. RESULTS:
      Hip extensor strength correlated positively with box jerk, as did box jerk and
      peak trunk angular momentum between subjects. There was an inverse correlation
      between peak upper body angular momentum when lifting a box from floor to knee
      height, and gait speed normalized to body weight. There was a positive
      correlation between trunk angular momentum during lifting and trunk angular
      momentum during chair rise. CONCLUSION: Stronger subjects used more peak vertical
      box jerk and more trunk peak angular momentum to lift a box from floor to knee
      height. Stronger subjects who used more HAT angular momentum during free speed
      chair rise also used more trunk peak angular momentum during the first phase of
      the lift, but lifting characteristics were independent of gait velocity. Weaker
      subjects used less peak momentum and peak jerk, choosing instead a more
      conservative, and apparently more stable, lifting strategy. Before counseling
      elderly patients on proper body mechanics for lifting, clinicians should assess
      strength and functional status. Weak elders should be taught a lifting strategy
      that allows them to maintain optimal balance, and to lift without jerking the
      load.

PMID- 10917267
TI  - Adequacy of power wheelchair control interfaces for persons with severe
      disabilities: a clinical survey.
AB  - The extreme difficulty with which persons with severe disabilities have been
      taught to maneuver a power wheelchair has been described in case studies, and
      anecdotal evidence suggests the existence of a patient population for whom
      mobility is severely limited if not impossible given currently available power
      wheelchair control interfaces. Since our review of the literature provided little
      evidence either in support or refutation of the adequacy of existing power
      wheelchair control interfaces, we surveyed 200 practicing clinicians, asking them
      to provide information about their patients and to give their impressions of the
      potential usefulness of a new power wheelchair navigation technology. Significant
      survey results were: Clinicians indicated that 9 to 10 percent of patients who
      receive power wheelchair training find it extremely difficult or impossible to
      use the wheelchair for activities of daily living. When asked specifically about
      steering and maneuvering tasks, the percentage of patients reported to find these
      difficult or impossible jumped to 40. Eighty-five percent of responding
      clinicians reported seeing some number of patients each year who cannot use a
      power wheelchair because they lack the requisite motor skills, strength, or
      visual acuity. Of these clinicians, 32 percent (27 percent of all respondents)
      reported seeing at least as many patients who cannot use a power wheelchair as
      who can. Nearly half of patients unable to control a power wheelchair by
      conventional methods would benefit from an automated navigation system, according
      to the clinicians who treat them. We believe these results indicate a need, not
      for more innovation in steering interfaces, but for entirely new technologies for
      supervised autonomous navigation.

PMID- 10917268
TI  - Biofeedback therapy using accelerometry for treating dysphagic patients with poor
      laryngeal elevation: case studies.
AB  - Dysphagia, a swallowing disorder, is a problem encountered frequently in the
      rehabilitation of stroke and head injury patients. In normal individuals, safe
      passage of a food bolus into the esophagus is ensured by laryngeal elevation and
      closure of the airway. Inadequate laryngeal elevation can lead to aspiration,
      choking, and even death. The course of recovery in the current clinical practice
      is rather tedious. Recently, investigators have developed and evaluated the
      accelerometry technique for noninvasive assessment of laryngeal elevation. The
      purpose of the present paper is to present case reports of patients with poor
      laryngeal elevation treated with computerized biofeedback therapy using dynamic
      acceleration measurements. Acceleration was measured from the dysphagic patient
      during swallowing, and was dynamically displayed on the computer screen along
      with an acceleration signal from a typical, normal subject. The patient was asked
      to elicit a swallow response such that his/her acceleration display matched the
      display of the normal subject. Each patient had nine therapy sessions, lasting
      about half an hour each. All five patients improved significantly in acceleration
      magnitude and in swallowing function as confirmed by the videofluorography
      evaluation.

PMID- 10917270
TI  - A qualitative evaluation of an assisted self-help group for drug-addicted clients
      in a structured outpatient treatment setting.
AB  - We conducted a qualitative evaluation of a semi-structured, client-led support
      group that addressed drug use recovery issues and was assisted by a psychological
      consultant. Seven regular group members and their counselors were interviewed
      about the effect of the assisted self-help group on drug use and the clients'
      quality of life, and these interviews were content analyzed. In addition, the
      psychological consultant made group process observations for each session of the
      first three months. Clients reported group strengths as: Feeling supported and
      understood, being able to speak freely without fear of staff reprisals, obtaining
      information/feedback, improved mood, and decreased drug use. With the provision
      of professional support and guidance, this group shows promise as an adjunct to
      standard outpatient drug abuse treatment by allowing for some degree of client
      independence and extending the scarce resource of professional counseling.

PMID- 10917269
TI  - Design of the advanced commode-shower chair for spinal cord-injured individuals.
AB  - The purpose of this development project was to design a new commode-shower chair
      that can be safely used by individuals with spinal cord injuries (SCI) and their
      caregivers. The need for this new design was consumer-driven. Patients and
      caregivers identified the following fatal flaws in the commode-shower chairs used
      in Spinal Cord Injury (SCI) centers: 1) risk for patient falls during transfers,
      propelling, and while leaning over for showering; 2) risk for pressure ulcers due
      to inadequate padding and seat positioning for lengthy bowel care regimes; 3)
      inadequate caregiver access to the perianal area of the patient to perform bowel
      care procedures; and, 4) wheel-related inability to properly position the chair
      directly over the toilet. The new, self-propelled chair addresses each of these
      concerns. Lockable, swing-away, pivoting armrests and improved, lever-activated
      brakes were designed to facilitate safe transfers. An innovative foot-lift was
      invented to facilitate washing of feet. Larger handrims were designed to aid in
      propulsion in wet environments. To prevent pressure ulcers, a chair frame and
      padding combination was designed to facilitate a seating position that optimally
      distributes body weight to prevent the development of pressure ulcers in the
      sacral and ischial areas. To address the common risk of heel ulcers, footrests,
      featuring edgeless, rounded heel cups, were designed. A new tubular chair frame,
      a new seat and smaller wheels were designed to enhance caregiver access and
      ensure proper chair positioning over the toilet. Following its successful
      clinical evaluation at the Milwaukee and Tampa VA Medical SCI Centers, the
      Advanced commode-shower chair is being patented by the Department of Veterans
      Affairs (VA). The VA has partnered with Everest & Jennings, to make this chair
      available commercially.

PMID- 10917271
TI  - A description of precipitants of drug use among dually diagnosed patients with
      chronic mental illness.
AB  - In this report, we describe patients' perceptions of the chronological occurrence
      of their mental illness and substance abuse. The patients were enrolled in a
      community mental health center and received dual diagnosis treatment from an
      affiliated psychiatric rehabilitation program. Using a questionnaire designed to
      address this issue, we assessed patients' perceptions of support currently being
      received at the treatment program and how beneficial they perceived this support
      to be. In addition, we assessed why substance use was a coping strategy in times
      of perceived stress early in life and whether this behavior has changed to date.
      Assessing the perception of the sequence of co-occurring disorders among patients
      enables us to better understand the factors that precipitate substance use and
      exacerbate mental illness. This knowledge may aid in the design of effective
      treatment strategies for this population of patients.

PMID- 10917272
TI  - How are we doing? A statewide survey of community adjustment among people with
      serious mental illness receiving intensive outpatient services.
AB  - Although mental health consumers often prefer community living, the factors
      influencing community outcomes are not well understood. In order to address this
      issue in Connecticut, the Department of Mental Health and Addiction Services
      (DMHAS) commissioned a statewide study of 6,800 clients receiving the most
      intensive community-based mental health services funded by the state. DMHAS
      clinicians provided the ratings for their clients on a variety of variables
      including demographics, diagnosis, clinical stability, current psychotic
      symptomology, adherence to prescribed medications, substance abuse, history of
      violent crime, community trouble-making or victimization, likelihood of
      threatening behavior, frequency of social contacts, and difficulty in adjusting
      to life in the community. Also, the total length of stay and total number of
      admissions during a two year period were taken from the statewide management
      information system for each client in the study. Descriptive data analysis
      included frequencies and means to describe the demographic, the diagnostic, and
      the clinical profile of the DMHAS clients. A stepwise hierarchical multiple
      regression analysis (MRA) was performed to determine what factors predict a
      composite score of overall functioning, community adjustment, and psychiatric
      impairment. Clients with better composite scores were those who had a
      prescription for medications, adhered more to their medication regimen, perceived
      to be less threatening, and had more frequent social interactions. Implications
      of these findings for outpatient treatment are discussed.

PMID- 10917273
TI  - Characteristics of Latino mental health clinicians: a preliminary examination.
AB  - The purpose of this study was to explore a variety of characteristics of
      experienced Latino psychotherapists in an attempt to clarify elements of cultural
      competence. The sixty five subjects were from a sample of convenience recruited
      from mental health agencies serving predominantly Latino clients in the San
      Francisco Bay area. The first part of the study consisted of two focus groups
      with Latino clinicians to discuss culturally competent services and to generate
      ideas to inform a preliminary questionnaire. The second part consisted of
      administering the questionnaire to the sample. Results were mixed, revealing a
      combination of responses indicating clinical interventions based upon universally
      accepted principles, and those uniquely used with Latino clients which were more
      clearly associated with the cultural traits of Latinos.

PMID- 10917274
TI  - Evaluation of expanded school mental health programs.
AB  - Expanded school mental health programs provide a full range of mental health
      services (assessment, treatment, case management, prevention) to youth in regular
      and special education, and typically involve close collaboration between schools
      and community agencies. A major challenge for these programs is documenting that
      provided services are of high quality and leading to enhanced outcomes for the
      youth and schools served by them. Dimensions of school mental health evaluations
      and a step-by-step process for conducting them are presented, using the example
      of a well established program in Baltimore. Challenges to such evaluation and
      strategies for overcoming challenges are also presented.

PMID- 10917275
TI  - Journey of Hope program outcomes.
AB  - Families of persons with mental illness often benefit from participating in
      interventions which provide education and support. The present study describes
      outcomes reported by 424 families who participated in one such intervention, the
      Journey of Hope (JOH) program. Hierarchical regression analyses found that
      program outcomes-increased knowledge of the causes and treatment of mental
      illness, increased understanding of the mental health service system, and
      improved morale-were predictive of one another. JOH therefore may provide
      families with the knowledge and support they need to strengthen their ability to
      cope with their relative's mental illness.

PMID- 10917276
TI  - Recovery and serious brain disorders: the central role of families in nurturing
      roots and wings.
AB  - Recovery in severe mental illness is a powerful concept for consumers, invoking a
      journey through understanding and acceptance of illness and disability, along
      with hope for a quality life, self-empowerment, and responsibility. Although not
      widely recognized, the journey toward recovery is also important for family
      members of individuals with severe mental illnesses, who often serve in a care
      giving or supportive role for their loved ones. From the family perspective, to
      make recovery a real possibility, several issues must be confronted. First,
      progress toward recovery must acknowledge and involve care-giving and supportive
      family members, recognizing their significant role in the lives of many
      individuals with severe mental illnesses as well as the journey of family members
      in understanding and accepting a severe mental illness in a loved one. Second, a
      real, recovery-oriented system implements treatments and supports shown to be
      effective. In this day and age, the gap between research findings and ordinary
      care condemns too many consumers and their families to outcomes far short of what
      is possible. This includes not only medications, psychotherapy, employment
      services, dual diagnosis services, housing and other supports for consumers, but
      also family education, shown to be effective by a large body of research. Third,
      a recovery-oriented system of care cannot afford to dance around the thorniest
      and most controversial issues in severe mental illnesses-such as individuals with
      the most intractable forms of illness or the relatively infrequent but very real
      situations in which either consumers or family members are assaultive or abusive.
      All of these elements are essential if recovery is to be more than a slogan, but
      rather a true goal in a system of care that respects consumers with these
      disorders and their care-giving family members.

PMID- 10917277
TI  - Reflections on recovery.

PMID- 10917278
TI  - Comparison of skin staples with sutures for anastomosis of the small intestine in
      dogs.
AB  - OBJECTIVES: To develop a technique for approximation of end-to-end intestinal
      anastomoses by using a disposable skin stapler and to compare the stapling
      technique with an interrupted hand-sewn approximating end-to-end anastomosis of
      the canine jejunum. STUDY DESIGN: In vitro evaluation of the stapling technique,
      followed by an in vivo study of healing and clinical response in dogs. ANIMAL
      POPULATION: 18 mixed-breed adult dogs. METHODS: The anastomotic technique was
      developed and tested in fresh canine jejunum. Fourteen stapled approximating
      anastomoses (SAA) and 14 hand-sewn approximating anastomoses (HAA) were performed
      in 6 cadavers under simulated surgical conditions. Anastomotic construction
      times, initial bursting strengths, initial lumen diameters, and gross appearance
      of the 2 techniques were compared. Healing and clinical response were evaluated
      in 12 purpose-bred dogs assigned to 2 groups of 6 animals each. Each dog had 1
      SAA and 1 HAA performed in the jejunum, 50 cm apart. Six dogs were killed on
      postoperative day 4, and 6 dogs were killed on postoperative day 21. Anastomotic
      construction time, gross and histological healing, bursting strength, lumen
      diameter, and circumference were compared between techniques. RESULTS: Mean
      construction time for SAA was significantly faster than for HAA (P = .0001). None
      of the anastomoses leaked, and there were no major clinical complications in any
      dog. Bursting strengths were not significantly different at any time for the 2
      techniques. Initial bursting strength was 31% to 35% of the normal jejunum. A
      nonsignificant decrease in bursting strength was observed by postoperative day 4
      (26% to 28% of normal), and a significant increase in bursting strength was
      observed by postoperative day 21 (100% to 109% of normal). Neither technique
      decreased the initial lumen diameter. However, both techniques resulted in a
      similar degree of luminal stenosis as the anastomoses healed. Anastomotic lumen
      diameter was significantly decreased from normal in both groups at day 4 (86% to
      88% of normal) and day 21 (90% to 91% of normal). There was no significant
      difference between the circumference of the anastomoses and normal jejunum at any
      time. Histological analysis showed similar healing for the hand-sewn and stapled
      techniques at 4 and 21 days after surgery. For both surgical techniques, day 21
      anastomoses had significantly less inflammation and necrosis, significantly more
      fibrosis, and significantly better continuity of histological layers when
      compared with day 4 anastomoses. CONCLUSION: Approximating end-to-end intestinal
      anastomosis with a skin stapler is equivalent in bursting strength, lumen
      diameter, lumen circumference, and healing characteristics to the traditional
      hand-sewn technique, but it can be performed in significantly less time. CLINICAL
      RELEVANCE: Skin stapling devices can be used to create technically simple, rapid,
      and safe end-to-end anastomoses in canine jejunum.

PMID- 10917279
TI  - Sternal bone biopsy in standing horses.
AB  - OBJECTIVE: To develop a technique for sternal bone biopsy in standing horses.
      STUDY DESIGN: Experimental study. ANIMALS: Five adult horses. METHODS: Horses
      were restrained in a standing stocks and sedated. The sternal biopsy site,
      identified by ultrasonographic examination, was clipped and prepared for aseptic
      surgery and infiltrated with local anesthetic. An electric bone biopsy drill
      (Osteocore; Institut Straumann AG, CH-4437, Waldenburg, Switzerland)), which
      yielded 4-mm-diameter bone specimens, was used to obtain sternal biopsies through
      a small skin incision. Sections (7 microm) of the bone specimens were stained
      with toluidine blue and Goldner's green trichrome and observed microscopically to
      determine suitability for histological and histomorphometric evaluation. RESULTS:
      The most suitable sternal biopsy site was at the 4th or 5th sternebra. The
      surgical procedure was easy to perform and well tolerated by the horses, and
      adequate samples were obtained on the first attempt. The only complications were
      incisional edema in all horses and wound drainage in 1 horse. CONCLUSIONS:
      Sternal bone biopsy may be successfully performed in standing horses, and the
      technique described in this report yields architecturally intact bone specimens.
      CLINICAL RELEVANCE: The sternum is an accessible site for cancellous bone biopsy
      specimens in standing horses.

PMID- 10917280
TI  - Evaluation of a hemostasis model for teaching ovariohysterectomy in veterinary
      surgery.
AB  - OBJECTIVE: To evaluate the efficacy of a reusable plastic model mimicking the
      anatomy and hemodynamics of the canine female genital tract for teaching basic
      surgical skills and ovariohysterectomy. SAMPLE POPULATION: 40 veterinary students
      of the class of 1998. STUDY DESIGN: Prospective study. METHODS:
      Students'confidence level and experience in private practice was evaluated via
      questionnaire before training. Students in 2 groups performed an
      ovariohysterectomy on cadavers (group C, n = 20) or on the model (Group M, n =
      20) for 2 hours. Students' psychomotor and basic surgical skills were objectively
      assessed by the following tests: ligation of a foam cylinder, passing a needle
      through the eyelets of an electronic suture board, and ligating latex tubing.
      Results were compared before and after training and within and between groups.
      The ability of students to perform an ovariohysterectomy in a live dog after
      training was compared between groups with a scoring system. RESULTS: Students in
      both groups had similar surgical experience and basic skills before training. The
      results of the psychomotor and basic surgical skills tests were better in group M
      after training than group C. The improvement of each student in performing these
      tasks also increased when students were trained with the model. Scores assigned
      to students performing an ovariohysterectomy in a live dog were higher in group M
      (31.45 +/- 1.15) than in group C (20.7 +/- 1.42). CONCLUSION: The model was more
      effective than cadavers in teaching basic surgical skills and ovariohysterectomy
      in dogs.

PMID- 10917281
TI  - Cecal amputation within the right ventral colon for surgical treatment of
      nonreducible cecocolic intussusception in 8 horses.
AB  - OBJECTIVES: To report a surgical technique for treatment of nonreducible
      cecocolic intussusception and outcome in 8 horses. STUDY DESIGN: Retrospective
      study. ANIMALS: Eight horses with nonreducible cecocolic intussusception treated
      by cecal amputation through a right ventral colotomy. METHODS: Data were obtained
      from medical records and telephone conversations by using a standardized
      questionnaire. The large colon was exteriorized and, if necessary, evacuated of
      its contents through a pelvic flexure enterotomy. A second colotomy was made on
      the ventral surface of the right ventral colon (RVC) centered over or immediately
      distal to the intussusceptum. In most horses, attempts to manually reduce the
      intussusception by pushing the cecum from within the RVC through the cecocolic
      orifice were unsuccessful. Invaginated cecum was then pulled into the RVC and
      amputated; the cecum was either ligated with umbilical tape or sutured proximal
      to the site of amputation. After amputation, the remainder of the invaginated
      cecum was reduced. After further resection to healthy tissue, the typhlectomy was
      closed with a double-inverting suture pattern. RESULTS: The median horse age was
      2 years (range, 1 to 8 years). Duration of colic ranged from 6 hours to 6 months.
      Median surgical time was 180 minutes (range, 135 to 300 minutes). Median duration
      of antibiotic therapy was 7 days (range, 5 to 14 days). Median duration of
      hospitalization was 12 days (range, 6 to 21 days). All horses survived to
      hospital discharge. One horse died 3 months postoperatively; however, the
      remainder survived (median survival, 30 months; range, 6 to 96 months) and
      returned to or exceeded previous function. CLINICAL RELEVANCE: Despite some
      contamination during surgery, horses with nonreducible cecocolic intussusception
      that underwent this method of surgical treatment had a good prognosis.

PMID- 10917282
TI  - An in vitro comparison of cordopexy, cordopexy and laryngoplasty, and
      laryngoplasty for treatment of equine laryngeal hemiplegia.
AB  - OBJECTIVE: To examine the effect of cordopexy, laryngoplasty, and cordopexy
      combined with a modified laryngoplasty on airway mechanics. STUDY DESIGN:
      Experimental airway mechanics were determined by subjecting equine cadaveric
      larynges to airflows similar to inspiratory airflow of exercising horses. ANIMALS
      OR SAMPLE POPULATION: Twenty equine larynges. METHODS: Using cadaveric larynges,
      we developed and tested a new technique of arytenoid cartilage abduction. All
      larynges had the right arytenoid cartilage abducted to mimic the degree of
      arytenoid abduction that occurs at maximal exertion in live horses. Three
      surgical techniques were used to stabilize the left arytenoid cartilage of
      treated larynges; the left arytenoid cartilage was not stabilized in control
      larynges. Technique 1: Cordopexy--a suture was placed between the vocal ligament
      and the lamina of the thyroid cartilage. Technique 2: Standard laryngoplasty--a
      suture was placed between the muscular process of the arytenoid cartilage and the
      caudomedial aspect of the cricoid cartilage. Technique 3: Cordopexy plus modified
      laryngoplasty--the cordopexy suture was placed with a second suture between the
      horizontal ridge rostral to the muscular process of the left arytenoid cartilage
      and the lamina of the thyroid cartilage. Translaryngeal impedances (TI) were
      determined for each surgical technique by subjecting the larynges to increasing
      airflows and measuring the translaryngeal pressure differences. The arytenoid
      right to left angle quotient (RLQ) and the glottic cross-sectional area (CSA)
      were also measured. RESULTS: At maximal airflow, the adjusted means for the
      arytenoid RLQ and the TI for the cordopexy plus modified laryngoplasty (1.48 +/-
      0.04, 0.69 +/- 0.05 cm H2O/L/s) and the standard laryngoplasty (1.39 +/- 0.04,
      0.78 cm H2O/L/s) were different (P < .05) from values obtained after cordopexy
      alone (2.74 +/- 0.37, 1.76 +/- 0.48 cm H2O/L/s) or in control larynges (3.66 +/-
      0.54, 4.16 +/- 0.96 cm H2O/L/s). Overall, a cordopexy plus modified laryngoplasty
      (9.69 cm2), a standard laryngoplasty (9.34 cm2), and a cordopexy alone (9 cm2)
      resulted in an increased glottic CSA greater than that for control larynges (6.94
      cm2; P = .0001). CONCLUSIONS: Cordopexy alone did not improve airflow in a left
      laryngeal hemiplegic model. Cordopexy plus modified laryngoplasty was as
      efficacious as the standard laryngoplasty in alleviating the effects of left
      laryngeal hemiplegia on TI, glottic CSA, and arytenoid RLQ. CLINICAL RELEVANCE:
      Fixation of the vocal cord (cordopexy) in addition to a laryngoplasty procedure
      may prove useful in the surgical treatment of equine laryngeal hemiplegia.

PMID- 10917283
TI  - Long-term results of bovine mandibular fractures involving the molar teeth.
AB  - OBJECTIVE: To evaluate postoperative complications and long-term outcome of
      simple mandibular fractures involving the molar teeth in cattle. ANIMAL
      POPULATION: Seventeen cattle with mandibular fractures involving the molar teeth
      with disruption of the occlusal surface. METHODS: Treatment consisted of
      application of AO/ASIF-Pinless External Fixators (Synthes, Paoli, PA) in 14 cows,
      interdental wire stabilization in 1 cow, and conservative treatment in 2 cows.
      Long-term outcome was determined by telephone contact with the owners, and
      whenever possible, cows were reevaluated by physical, intraoral, and radiographic
      examination of the fracture site. RESULTS: Loosening of the fixation device (4
      cattle) and bone sequestration (11 cattle) were the most commonly encountered
      complications. Oral incontinence during rumination was a minor complication in 1
      cow. The mean (+/- SD) time the cattle were in production was 26 (+/- 14) months,
      with 10 cows still alive at follow-up examination; 9 cows were reevaluated. On
      intraoral examination there was a step in the occlusal surface at the level of
      the healed fracture site in 3 cows, wave and shear mouth formation in 3 cows, and
      enamel point formation in 1 cow. Radiographically, all the reevaluated fractures
      had healed, and there were no signs of tooth root infection. CONCLUSIONS:
      Complications during healing were bone sequestration and loosening of the
      fixator. None of the cows was removed from production because of fracture
      associated complications, but decreased milk yield occurred in 2 cows. Tooth
      abnormalities developed in 6 cows, but function of the mandible was not altered.
      CLINICAL RELEVANCE: Mandible fractures involving the molar teeth carry a good
      prognosis for return to normal function. Radiographic follow-up is necessary to
      detect bone sequestration.

PMID- 10917284
TI  - Synovial fluid analysis in cattle: a review of 130 cases.
AB  - OBJECTIVE: To compare synovial fluid characteristics of cattle with infectious
      and noninfectious arthritis. STUDY DESIGN: Retrospective cohort study. ANIMAL OR
      SAMPLE POPULATION: 130 cattle. METHODS: Synovial fluid was analyzed for total
      nucleated cell count (NCC), absolute number and percentages of polymorphonuclear
      (PMN) and mononuclear cells, total protein (TP) concentration, and specific
      gravity. Cattle were categorized as having infectious or noninfectious arthritis
      based on physical and lameness examinations, joint radiographs, and microbial
      culture results. Kruskal-Wallis 1-way analysis of variance was used to compare
      synovial fluid analysis data from different categories. Selection of cut-off
      values for the calculation of likelihood ratios, sensitivity, specificity, and
      positive and negative predictive values was based on examination of the
      distribution of the data using histograms. RESULTS: Cattle with infectious
      arthritis had significantly higher numbers of total NNC, PMN cells, TP
      concentration, and specific gravity (P = .0001) and a significantly higher
      percentage of PMN cells compared with cattle with noninfectious arthritis (P =
      .0001). The percentage of mononuclear cells was significantly higher in cattle
      with noninfectious arthritis (P = .0001). CONCLUSIONS: Synovial fluid analysis is
      useful for differentiation of infectious and noninfectious causes of joint
      disease in cattle. CLINICAL RELEVANCE: Cattle with a synovial fluid total NCC >
      25,000 cells/microL, a PMN cell count > 20,000 cells/microL or more than 80% PMN
      cells, and TP > 4.5 g/dL should be considered to have infectious arthritis.

PMID- 10917285
TI  - In vitro evaluation of the effect of dimethyl sulfoxide on equine articular
      cartilage matrix metabolism.
AB  - OBJECTIVE: To evaluate the effects of dimethyl sulfoxide (DMSO) on equine
      articular cartilage matrix metabolism. STUDY DESIGN: Using a cartilage explant
      culture system, proteoglycan (PG) synthesis, PG release, lactate metabolism,
      chondrocyte viability, and metabolism recovery were determined after cartilage
      exposure to DMSO. SAMPLE POPULATION: Cartilage harvested from metacarpophalangeal
      and metatarsophalangeal joints of 12 horses (age range, 1 to 10 years). METHODS:
      Explants were exposed to concentrations of DMSO (1% to 20%) for variable times (3
      to 72 hours). PG synthesis and release were determined by a radiolabel
      incorporation assay and dimethylmethylene blue (DMMB) dye assay, respectively.
      Lactate released into culture media was measured, and chondrocyte viability was
      assessed using the Formizan Conversion Assay and a paravital staining protocol.
      Metabolism recovery was assessed in explants that were allowed to recover in
      maintenance media after exposure to DMSO. RESULTS: PG synthesis and lactate
      metabolism were inhibited in a dose- and time-dependent manner after exposure to
      DMSO concentrations > or = 5%; there was no significant alteration in PG release.
      No change in chondrocyte viability was detected after incubation with DMSO. PG
      synthesis and lactate metabolism returned to baseline rates when allowed a
      recovery period after exposure to DMSO. CONCLUSIONS: DMSO concentrations > or =
      5% suppress equine articular cartilage matrix metabolism. Suppression of PG
      synthesis and lactate metabolism is reversible and does not appear to be the
      result of chondrocyte death. CLINICAL RELEVANCE: Equine clinicians adding DMSO to
      intraarticular lavage solutions should be aware that DMSO may have deleterious
      effects on equine articular cartilage matrix metabolism.

PMID- 10917286
TI  - In vitro biomechanical properties of 2 compression fixation methods for midbody
      proximal sesamoid bone fractures in horses.
AB  - OBJECTIVE: To evaluate 2 methods of midbody proximal sesamoid bone repair-
      fixation by a screw placed in lag fashion and circumferential wire fixation--by
      comparing yield load and the adjacent soft-tissue strain during monotonic
      loading. STUDY DESIGN: Experimental study. SAMPLE POPULATION: 10 paired equine
      cadaver forelimbs from race-trained horses. METHODS: A transverse midbody
      osteotomy of the medial proximal sesamoid bone (PSB) was created. The osteotomy
      was repaired with a 4.5-mm cortex bone screw placed in lag fashion or a 1.25-mm
      circumferential wire. The limbs were instrumented with differential variable
      reluctance transducers placed in the suspensory apparatus and distal sesamoidean
      ligaments. The limbs were tested in axial compression in a single cycle until
      failure. RESULTS: The cortex bone screw repairs had a mean yield load of 2,908.2
      N; 1 limb did not fail when tested to 5,000 N. All circumferential wire repairs
      failed with a mean yield load of 3,406.3 N. There was no statistical difference
      in mean yield load between the 2 repair methods. The maximum strain generated in
      the soft tissues attached to the proximal sesamoid bones was not significantly
      different between repair groups. CONCLUSIONS: All repaired limbs were able to
      withstand loads equal to those reportedly applied to the suspensory apparatus in
      vivo during walking. CLINICAL RELEVANCE: Each repair technique should have
      adequate yield strength for repair of midbody fractures of the PSB immediately
      after surgery.

PMID- 10917287
TI  - One-lung versus two-lung ventilation in the closed-chest anesthetized dog: a
      comparison of cardiopulmonary parameters.
AB  - OBJECTIVE: To evaluate cardiopulmonary effects of one-lung ventilation (OLV)
      versus two-lung ventilation (TLV) in closed-chest anesthetized dogs. STUDY
      DESIGN: Controlled, randomized experiment. ANIMALS: Fourteen, 2- to 7-year-old
      adult dogs, weighing 23 +/- 6 kg. METHODS: The dogs were anesthetized with
      acepromazine, morphine, thiopental, and halothane in oxygen, ventilated, and
      paralyzed with vecuronium. Tidal volume was 10 mL/kg. Respiratory rate was set to
      maintain end-tidal CO2 (ETCO2) at 40 +/- 2 mm Hg before instrumentation then not
      changed. The left bronchus of 7 dogs was obstructed with a Univent bronchial
      blocker (Fuji Systems Corp, Tokyo, Japan). Blood gas analysis and hemodynamic
      measurements were taken at predetermined intervals for 1 hour in the TLV group
      and at baseline and following bronchial obstruction in the OLV group. RESULTS:
      Shunt fraction was not significantly different between groups, but in OLV shunt
      increased from baseline at 5 minutes. Arterial oxygen (PaO2) decreased after
      baseline in OLV compared with TLV. Arterial carbon dioxide (PaCO2) increased with
      OLV and decreased with TLV. In OLV, systemic vascular resistance was variable and
      decreased compared with TLV. Cardiac index increased over time in both groups but
      was not affected by treatment. Heart rate, mean arterial pressure, and diastolic
      arterial pressure increased with OLV compared with TLV but did not change over
      time. CONCLUSION: This study shows that OLV statistically decreases oxygen
      tension and transiently increases shunt fraction, but with 100% O2 it appears to
      be a feasible procedure with minimal cardiopulmonary side effects in healthy
      dogs. CLINICAL RELEVANCE: OLV is a feasible procedure in anesthetized dogs to
      better facilitate thoracic procedures such as bronchopleural fistula repair and
      thoracoscopy.

PMID- 10917288
TI  - Pathogenesis of Hirschsprung's disease.
AB  - Hirschsprung's disease is an inherited disorder showing incomplete penetrance and
      variable expressivity. Genetic mapping and mutation screening of candidate genes,
      together with the study of several natural and knockout animal models, clearly
      have shown the involvement of several different genes in the pathogenesis of
      Hirschsprung's disease. Among these genes, the RET proto-oncogene accounts for
      the highest proportion of both familial and sporadic cases, with a wide range of
      mutations scattered along its entire coding region. The low detection rate of RET
      mutations in Hirschsprung patients also led to different hypotheses, such as the
      existence of additional Hirschsprung genes. Different animal and human genetic
      studies have identified 6 Hirschsprung genes: RET proto-oncogene (RET),
      endothelin 3 (EDN3), endothelin B receptor gene (EDNRB), glial-cell-line-derived
      neurotrophic factor (GDNF), endothelin converting enzyme (ECE1), gene encoding
      the Sry-related transcription factor SOX10 (SOX10). Microenvironmental factors
      also can play a role in the pathogenesis of aganglionosis. The developmental
      process of the crest-derived progenitor cells is sensitive to the level of
      different molecules. The expression deficit of different factors (GDNF, NTN) in
      the hindgut, in the absence of genetic mutations, could determine a missed
      activation of the receptor system, causing enteric neuroblast migration arrest.

PMID- 10917289
TI  - Pediatric surgery in Latin America.

PMID- 10917290
TI  - Early prediction of long-term survival and the timing of liver transplantation
      after the Kasai operation.
AB  - BACKGROUND/PURPOSE: The aim of this study was to determine early prognostic
      indicators for the prediction of long-term survival rate and timing of the liver
      transplantation after the Kasai operation. METHODS: A retrospective chart study
      was performed on 142 patients with biliary atresia (BA). The patients were
      divided in a success and a failure group, according to whether the patients serum
      bilirubin levels returned to normal (less than 1.0 mg/dL) within 3 months. The
      differences in survival rates and performance status between the 2 groups were
      analyzed statistically. RESULTS: The difference in cumulative survival rate
      between the 2 groups was striking. When the current status of the 40 patients who
      had survived for over 12 years was compared, 16 patients (53.3%) from the success
      group and 1 (9.1%) from the failure group had normal bilirubin levels, normal
      growth, no esophageal varix, and no hypersplenism. From the Kaplan-Meier survival
      curve, 3 types of deterioration were identified. Type 1 was death within 3 years.
      In type 2, deterioration occurred from 4 to 13 years. Type 3 was defined as
      unexpected deterioration in the success group, and its incidence was extremely
      low. CONCLUSIONS: Serum bilirubin level at 3 months after the Kasai operation can
      be used to predict long-term survival and the time when the onset of liver
      failure is likely to occur.

PMID- 10917291
TI  - The validity of bioelectrical impedance phase angle for nutritional assessment in
      children.
AB  - BACKGROUND/PURPOSE: Bioelectrical impedance analysis (BIA) is a quick and
      noninvasive method for estimating body composition. Many prediction equations
      have been reported recently using bioelectrical impedance to calculate fat free
      mass (FFM) and fat mass (FM). These equations are based on the assumption that
      the composition and density of FFM are stable. In children, the composition and
      density of FFM vary according to age and clinical state, so the use of these
      equations is limited. However, phase angle is directly determined from resistance
      (Rz) and reactance (Xc) without equations and reflects body cell mass. The
      authors, therefore, investigated the validity of phase angle for nutritional
      assessment in children. METHODS: Bioelectrical impedance analysis and
      anthropometric measurements were performed in 81 patients, including 71 well
      nourished and 10 malnourished children. RESULTS: Phase angle correlated with body
      weight (R = 0.818) and arm muscle circumference (r = 0.901) in well-nourished
      children. Malnourished patients showed lower phase angle than that of well
      nourished children. CONCLUSION: Bioelectrical impedance phase angle is a useful
      parameter for nutritional assessment in children.

PMID- 10917292
TI  - A randomized trial comparing peripherally inserted central venous catheters and
      peripheral intravenous catheters in infants with very low birth weight.
AB  - BACKGROUND/PURPOSE: To determine whether percutaneously inserted central venous
      catheters (PICC) and peripheral intravenous catheters (PIV) in infants with very
      low birth weight (VLBW) differ with respect to (1) incidence of sepsis, (2)
      number of insertion attempts and catheters required for total intravenous
      therapy, (3) courses of antibiotics, and (4) total duration of intravenous (IV)
      use. METHODS: A randomized comparative trial was conducted involving 63 VLBW
      infants (<1,251 g) who required IV therapy. Infants were assigned randomly at 1
      week of age to either a PIV or a PICC catheter and followed up prospectively
      until an IV was no longer required or the infant was transferred out of the
      neonatal intensive care unit. RESULTS: Data were analyzed on an intention-to
      treat basis. There was no difference in the incidence of sepsis (P = .64), number
      of courses of antibiotics (P = .16), or total duration of IV use (P= .34) between
      the 2 groups. The number of insertion attempts required for total IV therapy was
      significantly lower in the PICC group than in the PIV group (P = .008). There
      also was a significantly lower number of total catheters utilized in the PICC
      group (P = .002). When data were controlled for birth weight strata the results
      were similar. CONCLUSION: PICC lines reduced the number of painful IV procedures
      in VLBW infants without additional morbidity.

PMID- 10917293
TI  - The effects of a pediatric unilateral inguinal hernia clinical pathway on quality
      and cost.
AB  - BACKGROUND/PURPOSE: The purpose of this study is to discover whether a pediatric
      inguinal hernia surgical clinical pathway (CP) reduces the frequency of wound
      infections, return visits, times associated with surgical repair, or costs.
      METHODS: A multidisciplinary team developed the inguinal hernia surgical clinical
      pathway. Healthy children greater than 50 weeks gestational age who required
      unilateral hernia repair were considered for the study. Two groups were formed:
      (1) an intervention group selected randomly (n = 46, CI = 95%, power = .80) from
      patients enrolled from November 1996 through April 1997, and (2) a retrospective
      cohort control group (n = 46) matched to each intervention patient by age,
      gender, and medical history. Analysis of variance and chi2 testing were used to
      test for significant differences between the 2 groups in postoperative wound
      infections, readmission and emergency department return visits within 72 hours,
      times associated with surgical repair, and costs. RESULTS: There were no
      significant differences in postoperative wound infections, times associated with
      surgical repair, or readmission rates within 72 hours. Total cost significantly
      decreased, by 10% (P< or = .05), for pathway patients ($982 v $880). CONCLUSION:
      These results show that the use of a pediatric inguinal hernia surgical clinical
      pathway is associated with reduced cost while maintaining quality of care.

PMID- 10917295
TI  - Neural electrophysiological studies on the external anal sphincter in children
      with anorectal malformation.
AB  - BACKGROUND/PURPOSE: Abnormality of innervation of external anal sphincter is one
      of the most important factors affecting postoperative anorectal function. The
      abnormalities of lumbosacral nerves have been reported in many radiological and
      histopathologic studies. There are few reports on the neurophysiological changes
      in children with anoractal malformation. The aim of this study was to examine the
      functional changes of nerves to the external anal sphincter in anorectal
      malformation. METHODS: Forty-five patients with anorectal malformation underwent
      studies of latencies of pudendo-anal reflex, spinoanal response, and evoked
      potential of cauda equine simultaneously. The conduction time of afferent nerve,
      efferent nerve, and sacral spinal center of pudendo-anal reflex arc were analyzed
      quantitatively. RESULTS: The latencies of pudendo-anal reflex, spino-anal
      response, and conduction time of sacral spinal center significantly are prolonged
      in patients with anorectal malformation (P< .05). There was significant
      difference between rectourethral fistula group and vestibular fistula group as
      well as low-type deformity group. The patients with lumbosacral anomalies such as
      lumbosacral spinal bifida or absence of S4 or S5 had prolonged latencies,
      especially the pudendo-anal reflex latency. There was significant negative
      correlation between the latencies and clinical scores. Although pudendoanal
      reflex latency was longer in patients who had posterior sagittal anorectoplasty
      than those who had abdominoperineal pull-through procedure, the difference was
      not significant. CONCLUSIONS: The abnormality of nerves to external anal
      sphincters is one of the important causes for clinical outcome. The neural
      lesions vary in each type of anal and lumbosacral deformity.

PMID- 10917294
TI  - Total parenteral nutrition-associated intrahepatic cholestasis in infants: 25
      years' experience.
AB  - BACKGROUND/PURPOSE: There are few long-term chronological reviews examining the
      incidence of total parenteral nutrition (TPN)-associated intrahepatic cholestasis
      (TPNAC) in infants. The authors therefore reviewed TPNAC in their 25-year series,
      and also looked at the current problems associated with TPN in infants. METHODS:
      Two hundred seventy-three surgical neonates who received TPN for more than 2
      weeks were divided into 3 groups chronologically: group A (1971 through 1982, n =
      77), group B (1983 through 1987, n = 72), and group C (1992 through 1996, n =
      124). TPNAC was defined as serum direct bilirubin (DB) level greater than 2.0
      mg/dL during the neonatal period. RESULTS: The incidence of TPNAC in groups A, B
      and C was 57%, 31%, and 25% (P< .01), respectively, and the mortality rate from
      TPN-associated complications was 13%, 3%, and 3% (P< .05), respectively. Over the
      last 5 years, severe TPNAC developed in 20 patients (16%). Four of 20 died of TPN
      associated sepsis with hepatic failure; 2 had hypoganglionosis with intractable
      stagnant enteritis and subsequent sepsis, and 2 had fatal respiratory or cardiac
      disease. CONCLUSIONS: The incidence of TPNAC in surgical neonates and TPN
      associated mortality rates have decreased significantly. The mortality rate,
      however, still remains at 3%. Two of 4 fatal cases had hypoganglionosis, which
      were totally dependent on TPN. In patients who require long-term TPN, TPN still
      has unsolved problems, and small bowel transplantation may be indicated.

PMID- 10917297
TI  - A standardized feeding regimen for hypertrophic pyloric stenosis decreases length
      of hospitalization and hospital costs.
AB  - BACKGROUND/PURPOSE: Before the institution of a standardized feeding regimen
      (SFR) for hypertrophic pyloric stenosis (HPS) at the authors' institution, the
      postoperative feeding regimen and, thus, the length of hospitalization for HPS
      patients was variable. The aim of this study was to evaluate whether a SFR would
      affect the length of hospitalization or hospital costs for HPS patients. METHODS:
      A 5-year retrospective analysis was performed on 242 patients who underwent
      pyloromyotomy via a standard right upper quadrant incision. The length of
      hospitalization and hospital costs were compared in these patients before and
      after the institution of a standardized postoperative feeding regimen. RESULTS:
      The SFR decreased total length of hospitalization by 19.4% (3.1 days v2.5 days, P
      = .002), postoperative length of stay by 21% (1.9 days v 1.5 days, P< .001),
      total costs by 11.9% (P= .05), direct costs by 7.7% (P= .22), and indirect costs
      by 18.6% (P= .003). This occurred despite a small increase in costs per day. The
      SFR did not change the complication rate (5.3% before SFR v6.1% after SFR, P =
      1.0). CONCLUSION: A postoperative standardized feeding regimen for patients with
      HPS decreased length of hospitalization and hospital costs without adverse
      effects.

PMID- 10917296
TI  - Posterior sagittal approach: megasigmoid resection and anal reconstruction for
      severe constipation and fecal incontinence after anoplasty.
AB  - PURPOSE: The aim of this study was to present the technique of megasigmoid
      resection and anal reconstruction by complete posterior sagittal approach for the
      children with severe constipation and fecal incontinence after anoplasty.
      METHODS: Six patients (age, 2 to 18 years) born with imperforate anus and
      originally treated with perineal anoplasty suffered from intractable constipation
      and fecal incontinence. Contrast enema showed massive dilated and aperistaltic
      rectosigmoid colon with fecal impaction. Resection of the dilated bowel and anal
      reconstruction were completely performed by posterior sagittal approach. RESULTS:
      The mean operating time was 205 minutes (range, 125 to 265 minutes) and the
      average length of resected colon was 23.3 cm (range, 10 to 40 cm). There were no
      intraoperative or postoperative complications. By 2 to 4 months after the
      operation, all patients obtained voluntary bowel movement. On follow-up at 6 to
      24 months postoperative, no patient had constipation or required use of the
      laxatives again. Four of 6 patients suffered from grade 1 soiling, and the other
      2 had grade greater than 1 soiling. None had urinary retention or incontinence
      after the procedure. CONCLUSION: Resection of dilated rectosigmoid colon and anal
      reconstruction for the patients with severe constipation and fecal incontinence
      after anoplasty can be performed successfully using a posterior sagittal
      approach.

PMID- 10917298
TI  - 'Spontaneous' neonatal gastric perforation: is it really spontaneous?
AB  - BACKGROUND/PURPOSE: Most historical reports have described gastric perforation in
      the neonatal population as "spontaneous." More recently, several variables,
      including prematurity and nasal ventilation, have been implicated as contributing
      factors. The authors sought to analyze the etiology, course, and outcome of
      newborns with spontaneous gastric perforation from one institution over a 16-year
      period. METHODS: The authors reviewed retrospectively the charts of all infants
      who underwent operation or had perforation of the stomach diagnosed in the
      newborn period. RESULTS: Among more than 84,000 live births, 7 newborns were
      identified with perforation of the stomach. Four had coexisting gastrointestinal
      lesions (2 necrotizing enterocolitis, 1 undiagnosed tracheoesophageal fistula, 1
      meconium plug), and 1 received nasal continuous positive airway pressure (CPAP).
      In only 2 cases were no other gastrointestinal lesions or other presumed
      contributing factors (nasal CPAP) present, and thus, only 2 cases could be
      classified as "spontaneous." Mortality rate was 57%. Three of the patients were
      premature, all of whom died. CONCLUSIONS: Whereas in the older literature, most
      cases of gastric perforation were considered spontaneous, and were full term, the
      authors' review of 7 cases over a 16-year period leads us to question the cause
      as spontaneous. The authors found that prematurity and concomitant
      gastrointestinal lesions were associated with gastric perforation in the neonate
      and that few cases truly are spontaneous. The authors suggest that when gastric
      perforation occurs in neonates, a contributing cause should be sought.

PMID- 10917299
TI  - Serum hyaluronan and its association with unfavorable histology and
      aggressiveness of heterotransplanted Wilms' tumor.
AB  - BACKGROUND/PURPOSE: The sera and urine of children with Wilms' tumor (WT) often
      contain increased concentrations of hyaluronan (HA). The authors developed a
      heterotransplant model to investigate whether serum HA concentrations could
      predict the histology and progression of WT. METHODS: Random portions of 8 human
      WT specimens (7 favorable and 1 unfavorable histology findings) were
      heterotransplanted into the flanks of severe combined immunodeficient (SCID)
      mice. After 6 to 20 weeks of observation, animals were killed, and serum HA
      concentrations, tumor histology, and local invasion were determined. RESULTS:
      Sera of mice supporting tumor growth had a median HA concentration of 9,379
      microg/L (range, 459 to 3,206,176 microg/L) compared with a median HA
      concentration of 416 microg/L (range, 204 to 782 microg/L) in animals not
      supporting tumor growth. The highest serum HA concentrations were detected in
      animals harboring unfavorable histology blastemal-predominant tumors, whereas
      animals supporting favorable histology epithelial- and stromal-predominant tumors
      had the lowest serum HA concentrations. In association with markedly increased
      serum HA, undifferentiated blastemal tumors showed significantly greater growth
      rates than the more differentiated epithelial or stromal tumors. Additionally,
      serum HA concentrations were greater in mice with invasive as compared with
      noninvasive tumors for each histological type. Complete resection of established
      tumors also resulted in the return of serum HA to preheterotransplant
      concentrations. Identification of tumor progression was further tested in SCID
      mice receiving subcutaneous flank injections of the human WT cell line, SK-NEP-1.
      Significantly greater serum HA concentrations again corresponded with more rapid
      growth rates and invasiveness. CONCLUSIONS: Serum HA concentrations predict the
      growth, invasion, and unfavorable histology findings of WT in a heterotransplant
      model. The authors further speculate that HA may foster an environment conducive
      to WT aggressiveness.

PMID- 10917300
TI  - Recombinant human interleukin-11 prevents mucosal atrophy and bowel shortening in
      the defunctionalized intestine.
AB  - BACKGROUND: Mucosal atrophy and bowel shortening are the hallmark of proximal
      intestinal diversion for extensive necrotizing enterocolitis (NEC) or Thiry-Vella
      fistulas (TVF), in which the ends of a defunctionalized loop of intestine are
      exteriorized as stomas. Recombinant human interleukin-11 (rhIL-11) is a
      pleiotropic cytokine that promotes epithelial regeneration and enhances
      adaptation after bowel resection. The authors hypothesized that rhIL-11 may
      prevent mucosal atrophy and bowel shortening in rats with TVF METHODS: After
      creation of ileal TVF, Sprague-Dawley rats were selected randomly to receive
      either rhIL-11 or equal volume of 0.1% bovine serum albumin (BSA) subcutaneously
      daily. On day 14, the TVF were excised and examined morphologically. Enterocyte
      apoptosis was measured using the TUNEL assay. Mucosal DNA and protein content
      were measured. RESULTS: Administration of rhIL-11 resulted in a significantly
      greater weight gain and less shortening of TVF than BSA treatment. TVF from the
      rhIL-11-treated group showed evidence of hyperplasia and hypertrophy and
      increased crypt to villus ratio. The BSA group had substantial mucosal atrophy.
      There was a qualitative decrease in the incidence of apoptosis in the rhIL-11
      group. CONCLUSIONS: Recombinant human IL-11 prevents mucosal atrophy and
      shortening of defunctionalized intestinal loops. It may help reduce the incidence
      of short gut syndrome in infants with extensive NEC.

PMID- 10917301
TI  - Abdominal pain and appendicitis: is there a difference in referrals between HMO
      pediatricians and private pediatricians?
AB  - BACKGROUND: In the last few years, there have been many reports of the rising
      incidence of late appendicitis and perforated appendicitis. The rise of managed
      care medicine has been blamed for this, because the health maintenance
      organizations (HMO) and gatekeepers allegedly want to keep the child away from
      the surgeon and hospital to save costs. METHODS: The authors were in a unique
      position a number of years ago because they had only a single HMO in their area
      of practice (New Brunswick, NJ) employing 14 pediatricians, and 86 pediatricians
      were in private practice or on the medical school staff. The HMO had a yearly
      contract with the pediatric surgeons, and all visits and surgeries were covered
      by a yearly agreement (capitated agreement). The authors compared the number of
      children with appendicitis, perforated appendicitis, or just abdominal pain (not
      requiring surgery), between both groups over a 5-year period (1991 to 1996).
      RESULTS: A total of 492 patients were referred with abdominal pain over a 5-year
      period. Two hundred eight (42%) had appendicitis, and 284 (58%) had just
      abdominal pain and eventually were sent home. The HMO pediatricians diagnosed
      appendicitis accurately in 46% of their patients (55 of 118), and 54% were
      abdominal pain that was not appendicitis (63 of 118). For the private
      pediatricians, the percentages were: 40% of their patients had appendicitis (153
      of 374), and 60% had abdominal pain without appendicitis (221 of 374). The
      incidence of perforated appendicitis was similar (28% HMO v 30% private), and the
      incidence of negative explorations were similar (8% HMO v 9% private).
      CONCLUSIONS: The results are very similar in both groups, with a similar
      percentage of abdominal pain not being appendicitis (60% v 54%). HMO patients did
      not pay for consultations, and the HMO was not charged for any consultations.
      However, it does not appear that they overused the consultations for abdominal
      pain that were not appendicitis. Their accuracy for correct diagnosis of
      appendicitis was similar to the private group (46% v 40%), and the incidence of
      perforated appendicitis for both groups was 28% to 30%. The authors cannot draw
      any conclusions from their experience that HMOs in general do refer patients to
      surgeons in a timely fashion, and do not delay the referrals to avoid the cost of
      consultation, because the authors had a capitated agreement with their HMO, and
      consultations were free. Both groups of pediatricians, the HMO and the private
      pediatricians, did not realize financial gain or loss by sending children to the
      pediatric surgeon and were not penalized by sending patients with abdominal pain
      to the surgeon. On the contrary, their referral habits and judgments were similar
      and did not appear to change by being part of an HMO.

PMID- 10917303
TI  - The clinical presentation and outcome of treatment of congenital muscular
      torticollis in infants--a study of 1,086 cases.
AB  - BACKGROUND/PURPOSE: The main objectives of this study were to define the clinical
      patterns and characteristics of congenital muscular torticollis (CMT) presented
      in the first year of life and to study the outcome of different treatment
      methods. METHODS: This is a prospective study of all CMT patients seen in 1
      center over a 12-year period with uniform recording system, assessment methods,
      and treatment protocol. RESULTS: From a total of 1,086 CMT infants, 3 clinical
      subgroups of sternomastoid tumor (SMT; 42.7%), muscular torticollis (MT; 30.6%),
      and postural torticollis (POST; 22.1%) were identified. The SMT group was found
      to present earlier within the first 3 months and was associated with higher
      incidence of breech presentation (19.5%), difficult labor (56%), and hip
      dysplasia (6.81%). Severity of limitation of passive neck rotation range (ROTGp)
      was found to correlate significantly with the presence of SMT, bigger tumor size,
      hip dysplasia, degree of head tilt, and craniofacial asymmetry. CONCLUSIONS: A
      total of 24.5% of the patients with initial deficits of passive rotation of less
      than 10 degrees showed excellent and good outcome with active home positioning
      and stimulation program. The remaining cases with rotation deficits of over 10
      degrees and treated with manual stretching program showed an overall excellent to
      good results in 91.1% with 5.1% requiring subsequent surgical treatment. The most
      important prognostic factors for the necessity of surgical treatment were the
      clinical subgroup, the ROTGp, and the age at presentation (P < .001).

PMID- 10917302
TI  - Pyloroplasty improves long-term gastric emptying in rats undergoing
      fundoplication.
AB  - BACKGROUND: Conflicting reports exist regarding the permanence of improved
      gastric emptying (GE) after fundoplication for gastroesophageal reflux in
      children. METHODS: Changes in gastric volume (GV) and GE of a radiolabeled mixed
      meal induced by a Nissen fundoplication (NF) were compared with those with a NF
      plus pyloroplasty (NF + P). GE was measured preoperatively, 15 and 30 days
      postoperation, in 24 Sprague-Dawley rats; 12 had NF alone, and 12 had NF + P
      Results were expressed as percent gastric retention at 90 minutes (GR90). GV was
      measured at the same time periods in 20 additional rats. RESULTS: NF rats had
      enhanced GE with reduction of preoperative GR90 from 37.6% to 23.7% at 15 days (P
      < .05); however, at 30 days the GR90 increased to 34.3%. NF + P rats had enhanced
      GE with reduction in GR90 from 37.2% to 20.8% at 15 days (P< .05), which
      persisted at 30 days (20.4%). Mean GV decreased from (1.36 mL/100 g body weight)
      preoperation to 0.86 at 15 days (P< .05) at 15 days in the NF group, and returned
      to 1.29 at 30 days. Mean GV decreased from 1.36 to 0.91 at 15 days in the NF + P
      rats and persisted at 0.90 at 30 days. CONCLUSION: In the rat model, NF enhances
      GE transiently, whereas NF + P produces long-term enhancement of GE.

PMID- 10917304
TI  - Resorbable bioscaffold for esophageal repair in a dog model.
AB  - PURPOSE: Porcine-derived, xenogeneic extracellular matrix (ECM) derived from
      either the small intestinal submucosa (SIS) or urinary bladder submucosa (UBS)
      was used as a tissue scaffold for esophageal repair in a dog model. METHODS:
      Patch defects measuring approximately 5 cm in length and encompassing 40% to 50%
      of the circumference of the esophagus or complete circumferential segmental
      defects measuring 5 cm in length were created by surgical resection in healthy
      adult female dogs. The defects were repaired with ECM scaffolds derived from
      either SIS or UBS. The animals were kept alive for periods ranging from 4 days to
      15 months. RESULTS: The xenogeneic scaffolds used for repair of the patch defects
      were resorbed completely within 30 to 60 days and showed replacement by skeletal
      muscle, which was oriented appropriately and contiguous with adjacent normal
      esophageal skeletal muscle, organized collagenous connective tissue, and a
      complete and intact squamous epithelium. No signs of clinical esophageal
      dysfunction were seen in any of the animals with the patch defect repair. The
      xenogeneic scaffolds configured into tubes for repair of the segmental defects
      all showed stricture within 45 days of surgery. CONCLUSION: These ECMs show
      promise as a treatment option for esophageal repair, but stricture remains
      problematic for complete tube grafts.

PMID- 10917305
TI  - Laparoscopic surgery in children with ventriculoperitoneal shunts.
AB  - BACKGROUND/PURPOSE: Children with ventriculoperitoneal shunts may require
      laparoscopic surgery. The authors aimed to determine if this group of children
      are at greater risk for complications or technical problems. METHODS: Children
      with ventriculoperitoneal shunts who underwent laparoscopic surgery between 1995
      and 1998 were reviewed. In addition, the subset of children undergoing
      laparoscopic fundoplication were compared with the group of children without
      shunts who- had the same operation during the same period. RESULTS: Ten children
      with ventriculoperitoneal shunts underwent laparoscopic surgery. Three had
      complications, none of which were caused by the shunt. None had any evidence of
      shunt dysfunction related to the laparoscopic procedure. The 6 children with
      shunts who underwent laparoscopic fundoplication were compared with 17 similar
      children without shunts who underwent the same operation during the same period.
      There were no differences between the groups with respect to operating time,
      conversion to an open approach, or complications. CONCLUSION: Laparoscopic
      surgery can be performed safely and effectively in children with
      ventriculoperitoneal shunts.

PMID- 10917306
TI  - Pneumatosis cystoides intestinalis: a rare cause of nonsurgical pneumoperitoneum
      in an infant.
AB  - The authors describe a 3-year-old boy with pneumatosis cystoides intestinalis
      (PCI) and associated duodenal stenosis who came to them with abdominal pain,
      significant abdominal distension, large gastric residue, and pneumoperitoneum.
      PCI is a rare condition in children characterized by the presence of multiple gas
      filled cysts within the wall of some part of gastrointestinal tract that may
      break and cause pneumoperitoneum without an intestinal perforation. Even if in
      most cases the standard treatment is surgical, to keep in mind this rare
      condition could be useful to adopt a most rational treatment approach and avoid
      unnecessary operation in case of "benign" pneumoperitoneum.

PMID- 10917307
TI  - Benign pneumatosis intestinalis coli after blunt trauma to the abdomen in a
      child.
AB  - This report describes a 2 1/2-year-old boy who sustained blunt abdominal trauma
      and had pneumatosis intestinalis in the right colon. The child was successfully
      managed by observation. The pneumatosis resolved spontaneously.

PMID- 10917308
TI  - Posterior sagittal approach for Currarino syndrome with anterior sacral
      meningocele: a case report.
AB  - The authors report a case of Currarino syndrome with anterior sacral meningocele,
      tethered cord, and anorectal stenosis that was treated by posterior sagittal
      approach. Initially, a diverting colostomy was performed. Two months later,
      excision of the meningocele, untethering of spinal cord, and anorectoplasty were
      performed simultaneously without complication. Posterior sagittal approach seems
      to be very beneficial for excision of the presacral mass and reconstruction of
      the anus.

PMID- 10917309
TI  - Neonatal intestinal obstruction with isolated levocardia.
AB  - An unusual case of isolated levocardia, duodenal obstruction, and malrotation
      with volvulus is reported. Three cases of situs inversus abdominus with
      malrotation with volvulus have been reported to date. The current case is the
      fourth case and only the second survivor in the series. In cases of situs
      inversus abdominus, because of inversion of viscera, the volvulus may occur in an
      anticlockwise direction and, thus, should be derotated in a clockwise direction.

PMID- 10917310
TI  - Laparoscopic excision of a rare type II choledochal cyst: case report and review
      of the literature.
AB  - Although once considered rare, choledochal cysts now are extensively reported on
      and have an official anatomic classification. The authors report a case of a 4
      year-old girl whom on routine abdominal ultrasound as follow-up for
      vesicoureteral reflux was found to have a choledochal cyst. Follow-up
      hepatobiliary scan together with the ultrasound findings was consistent with a
      rare type II choledochal cyst. On laparoscopy, a type II choledochal cyst was
      confirmed on dissection and amenable to laparoscopic excision. Intraoperative
      cholangiogram after excision showed normal remaining biliary anatomy. The patient
      was discharged the following day without delayed complications on follow-up
      visits. This report suggests a role for laparoscopic surgery in the definitive
      management of selected cases of choledochal cystic disease. (Included is relevant
      radiological documentation, illustration of technique, and review of the
      literature.)

PMID- 10917311
TI  - Case report of a newborn with a posterior thoracic midline congenital
      hemangiopericytoma of the back.
AB  - The posterior thoracic midline location is an unusual site for a congenital
      hemangiopericytoma. The authors report such a case that caused near fatal
      exsanguination of a newborn after vaginal delivery. Magnetic resonance imaging
      (MRI) studies of the mass were completed after hemostasis. These studies showed a
      well-defined border between the tumor and underlying trapezius muscle. The mass
      was removed successfully surgically and presumed initially to be a teratoma.
      Pathological diagnosis of the tumor was hemangiopericytoma with low malignant
      potential. After a 9-day hospital course, the patient was discharged with
      recovering hepatic and renal function.

PMID- 10917312
TI  - Complex long-segment intestinal dysganglionosis.
AB  - A case is reported with aganglionosis of the rectum, sigma, and descending colon;
      dysganglionosis with heterotopic ganglionic cells in the muscularis propria of
      the hypoganglionic transverse colon; and extreme hypoganglionosis (without
      detection of ganglionic cells) of the ascending colon and distal ileum. The ileum
      showed a transition zone with hypoganglionosis and intestinal neuronal dysplasia
      (IND) type B. As to the etiology of such complex intestinal innervation defects,
      pre- and perinatal perfusion deficits must be considered because their
      localization seems to be linked to the vascular anatomy of the colon. Early
      diagnosis may be difficult, causing a delay in operative treatment and multiple
      operations. Different manifestations of dysganglionosis may be found in the same
      patient. The classical continuum of distal aganglionosis followed by proximal
      hypo- or dysganglionosis and then normally innervated bowel may not always be
      present. Therefore, in children with recurrent (sub-)ileus after resection of an
      aganglionic bowel segment, additional dysganglionosis such as IND or
      hypoganglionosis or even complex intestinal dysganglionosis should be excluded by
      full-thickness colon and small bowel biopsies.

PMID- 10917313
TI  - Childhood temporal bone osteoblastoma: a case report.
AB  - Osteoblastoma is a rare primary tumor of the bone. Its sites of predilection are
      the vertebrae and the long bones. Occurrence in the skull is rare. The authors
      describe an unusual case of osteoblastoma occurring in the temporal bone of a
      child. Interestingly, although the clinical and radiological features were
      suggestive of an aggressive lesion, the histological features were consistent
      with that of a benign tumor. Although generally regarded as benign, osteoblastoma
      has potential for recurrence, local invasion, and, rarely, malignant
      transformation. As such, complete resection, whenever possible, is preferred over
      conventional curettage.

PMID- 10917314
TI  - Arteriovenous malformation of the penis in an infant.
AB  - Arteriovenous malformations (AVMs) are common benign lesions in infancy, although
      they are rare in the genitourinary region. The authors report on a 2-year-old boy
      with a penile AVM. At presentation, there was venous dilatation and tortuosity of
      the prepuce without ulceration, which had been recognized at 1 year of age. Left
      internal iliac arteriography showed early venous filling leading to the diagnosis
      of AVM. Surgical excision was performed at age 2. The postoperative course was
      uneventful. At the 6-month follow-up, there was no evidence of recurrence. This
      is the first report of a penile AVM that was successfully treated by surgical
      excision.

PMID- 10917315
TI  - An unusual neck lump.
AB  - Oropharyngeal penetration and migration of ingested bodies into the neck is
      extremely rare. This is a case report of a 2-year-old boy who presented with a
      submental lump 1 day after swallowing a fish bone. The clinical, radiological,
      and intraoperative findings of the case are discussed.

PMID- 10917316
TI  - Effective treatment of infantile choriocarcinoma in the liver with chemotherapy
      and surgical resection: a case report.
AB  - Infantile choriocarcinoma of the liver is an extremely rare entity, and outcome
      has been fatal in almost all published cases. To the authors' knowledge, this is
      the first report on successful treatment with preoperative chemotherapy. A 10
      week-old girl presented with a large liver tumor, ovarian cysts, cardiac
      insufficiency, progressive hemolytic anemia, and thrombocytopenia. Ultrasound
      scan and magnetic resonance tomography (MRT) showed the typical pattern of
      infantile hemangioendothelioma. An emergency laparotomy was performed because of
      increasing cardiac insufficiency with ligation of the right hepatic artery, tumor
      biopsy, and subtotal resection of the ovarian cysts. Histology findings showed a
      choriocarcinoma of the liver and corpus luteum cysts of the ovaries. Serum beta
      human chorionic gonadotropin (beta-HCG) was elevated to 1.600.00 U/L.
      Chemotherapy was initiated with etoposide and cisplatin. When x-ray examination
      showed development of lung metastases, chemotherapy was intensified with
      etoposide, cisplatin, and ifosfamid according to the German Study Group of
      Extracranial Nontesticular Malignant Germ Cell Tumors in Childhood and
      Adolescence (MAKEI-96). Serum beta-HCG levels decreased further, ultrasound
      examination showed significant tumor reduction, and pulmonal metastasis could no
      longer be found in chest x-rays. After the fourth course, a complete tumor
      resection was achieved by an extended right hemihepatectomy with adjuvant
      chemotherapy being administered after the operation. The child has been in
      complete remission for 22 months. The authors' experience shows that chemotherapy
      is effective for preoperative tumor reduction.

PMID- 10917317
TI  - Unusual presentation of omphalomesenteric duct remnant: a variant of
      mesodiverticular band causing intestinal obstruction.
AB  - Two unusual cases of small bowel obstruction associated with an omphalomesenteric
      duct remnant are described in 2 girls aged 14 years. The causative factor was a
      stenotic area in the terminal ileum caused by a ringlike lipovascular mesenteric
      band encroaching externally on the lumen. A phytobezoar was lodged proximally.
      This is as yet an undescribed variant of a mesodiverticular band.

PMID- 10917318
TI  - Definitive treatment of congenital liver cyst with alcohol.
AB  - A full-term newborn boy presented with a palpable liver. Ultrasonography showed a
      solitary liver cyst. In 6 months the cyst grew 15-fold in volume. Intervention
      was deemed necessary because of large palpable abdominal mass in spite of the
      fact that the boy remained asymptomatic. Permanent resolution of the cyst was
      achieved by percutaneous ethanol injection-aspiration. At 7-year follow-up there
      has been no recurrence. The authors would like to draw attention to this
      minimally invasive alternative to surgery.

PMID- 10917319
TI  - A reevaluation of the mechanism of testicular descent: reasons for failed descent
      or ascent.

PMID- 10917320
TI  - Regulation of liver and kidney glucose-6-phosphatase gene expression in
      hemorrhage and resuscitation.
AB  - The authors have recently demonstrated that increased gene expression of glucose
      6-phosphatase (Glu-6-Pase) in hemorrhagic hypotension (HH) and following lactated
      Ringer's resuscitation (LR) is associated with a decrease in insulin and an
      increase in corticosterone concentrations. OBJECTIVE: To evaluate the in-vivo
      role of hormones the authors used insulin (IN), phentolamine and propranolol (PP)
      as an adrenergic blocker, and cyclic somatostatin (CS) as a glucagon blocker to
      prevent the induction of Glu-6-Pase gene expression in liver and kidney following
      HH and LR. METHODS: Hemorrhage was induced in fasted anesthetized rats, and the
      reduction of blood pressure to 40 mm Hg for a duration of 30 minutes was
      accomplished by withdrawal or infusion of shed blood. The resuscitated group
      underwent hemorrhage followed by fluid resuscitation with lactated Ringer's
      solution. RESULTS: Neither PP nor CS treatment could block the induction of Glu-6
      Pase messenger ribonucleic acid (mRNA) following either HH or LR. However, the
      administration of IN significantly prevented the increase of Glu-6-Pase mRNA
      level and activity in both liver and kidney following HH and LR. This was
      associated with a normalization of plasma glucose, corticosterone, and glucagon
      levels and glucose-6-phosphate concentrations in liver and kidney toward
      prehemorrhage levels. CONCLUSIONS: These results indicate that in-vivo treatment
      with insulin during hemorrhagic hypotension and resuscitation is capable of
      preventing the increase in Glu-6-Pase gene expression in liver and kidney
      responsible for the observed hyperglycemia.

PMID- 10917321
TI  - Variation in utilization of computed tomography scanning for the investigation of
      minor head trauma in children: a Canadian experience.
AB  - OBJECTIVES: To compare the utilization rates of CT scans in investigating minor
      head trauma in children in Canada, to identify the injuries determined by these
      scans, and to identify clinical findings that are highly associated with its
      diagnosis and the injury itself. METHODS: A retrospective cohort study involving
      nine pediatric hospitals in Canada was conducted. A structured data collection
      method was used. Inclusion criteria included age 16 years or less, history of
      blunt head trauma, and a Glasgow Coma Scale score (GCS) greater than or equal to
      13. Data collected included demographic information, type of injury, relevant
      clinical information, computed tomography (CT) scan data, and clinical outcome.
      Clinical findings associated with CT scan and positive CT scan were identified
      using logistic regression. RESULTS: One thousand one hundred sixty-four children
      were included in the study. One hundred seventy-one (15%) had a CT scan, of which
      60 (35%) were abnormal. There was a significant difference in the rate of
      ordering of CT scans among the participating hospitals, but no significant
      difference in the rate of abnormal CT scans. Mechanism of injury, GCS, and loss
      of consciousness were significantly related to the presence of an abnormal CT
      scan. CONCLUSIONS: Although there is a significant difference in the utilization
      of CT scans to investigate minor head trauma in children across Canada, there is
      no significant difference in the frequency of head injuries in these patients.
      This suggests that it may be possible to determine clinical criteria that are
      predictive of a head injury in these patients.

PMID- 10917322
TI  - Use of out-of-hospital interventions for the pediatric patient in an urban
      emergency medical services system.
AB  - OBJECTIVE: To determine appropriateness of out-of-hospital interventions by
      emergency medical services (EMS) personnel on children with respiratory
      illnesses. METHODS: A retrospective, cross-sectional study was performed on a
      random sample of 304 children transported by an urban EMS system during 1994.
      Data were abstracted from EMScan (a computerized database of all EMS dispatches)
      and the EMS narrative records. Appropriate utilization of interventions was
      determined by comparison with the standard EMS protocol for respiratory
      complaints in this system. An assessment of whether interventions were
      inappropriately underutilized or inappropriately overutilized was made. Effect of
      severity of illness, patient age, transport times, and use of medical command on
      the use of interventions was evaluated. RESULTS: Two hundred three patients (67%)
      were classified as having respiratory distress. Overall, 56% of the patients
      received appropriate interventions, 39% received one or two inappropriate
      interventions, and 5% received three or more inappropriate interventions. Rates
      of inappropriate utilization with 95% CI for each intervention were: oxygen 16%
      (95% CI = 12 to 20), assisted ventilation 2% (95% CI = 0.5 to 4), medication use
      9% (95% CI = 6 to 13), vascular access 11% (95% CI = 7 to 14), phlebotomy 9% (95%
      CI = 6 to 13), and cardiac monitoring 18% (95% CI = 14 to 22). Oxygen and
      medications were underutilized (p < 0.005), whereas vascular access, cardiac
      monitoring, and phlebotomy were overutilized (p < 0.005). Online medical command
      (used in 9% of transports) improved appropriate use of vascular access [OR 8.3
      (95% CI = 3 to 25) (p < 0.001)] and cardiac monitoring [OR = 3 (95% CI = 1 to 8)
      (p < 0.05)]. CONCLUSIONS: Emergency medical services personnel underutilized
      oxygen and medications and overutilized vascular access, phlebotomy, and cardiac
      monitoring in children with respiratory illness in this urban setting. Increasing
      patient age, transport times, and illness severity tend to increase the use of
      certain interventions, while contact with online medical direction seems to
      improve appropriate use of interventions.

PMID- 10917323
TI  - Pretreatment of lacerations with lidocaine, epinephrine, and tetracaine at
      triage: a randomized double-blind trial.
AB  - OBJECTIVE: Pretreatment of lacerations with topical anesthetics reduces the pain
      of subsequent anesthetic injection yet requires time. This study was conducted to
      determine the ability of triage nurses to identify lacerations necessitating
      closure and pretreat them with a topical anesthetic and to compare the pain
      levels of lidocaine injection in lacerations pretreated with LET (lidocaine 2%,
      epinephrine 1:1,000, tetracaine 2%) vs a placebo. METHODS: This was a double
      blind, randomized clinical trial that included consecutive emergency department
      patients aged > or = 1 year with clean, non-bite lacerations < or = 6 hours old.
      At triage the lacerations were randomized to LET solution or a placebo containing
      epinephrine 1:1,000. At examination an emergency practitioner assessed the
      laceration edges for the presence of blanching and adequacy of anesthesia to a 27
      gauge needlestick. At the practitioner's discretion, supplemental lidocaine was
      infiltrated through the wound and the patient (or guardian) recorded the pain of
      infiltration on a 100-mm visual analog scale marked "most pain" at the high end.
      The mean levels of pain of lidocaine infiltration were compared between groups
      with a t-test and the proportions of adequately anesthetized wounds were compared
      with a chi2 test. A sample of 40 patients had 80% power to detect a 20-mm between
      group difference in the pain of injection (alpha = 0.05). RESULTS: Of 43 patients
      enrolled (mostly children and males), 22 received LET and 21 placebo. The groups
      were similar for baseline characteristics. Lacerations in the LET group were more
      frequently adequately anesthetized (46% vs 14%, p = 0.03), and LET patients
      experienced less pain from injection than controls (22 mm vs 42 mm, p = 0.02).
      CONCLUSIONS: Application of LET by triage nurses is more effective than placebo
      in adequately anesthetizing simple lacerations in normal hosts and decreases the
      pain of local anesthetic infiltration.

PMID- 10917324
TI  - Care and outcome of out-of-hospital deliveries.
AB  - OBJECTIVES: To identify interventions by paramedics in out-of-hospital deliveries
      and predictors of neonatal outcome. METHODS: A prospective case series of
      consecutive out-of-hospital deliveries at Yale-New Haven Hospital from January
      1991 to January 1994. Data describing out-of-hospital interventions,
      demographics, maternal risk factors, and neonatal outcomes were collected from
      out-of-hospital, emergency department (ED), and hospital records. Subgroups
      defined by source of prenatal care were compared using a multiple-logistic
      regression model to determine predictors of poor neonatal outcome. RESULTS:
      Ninety-one patients presented to the hospital after delivery. Paramedics attended
      78 (86%) of the cases. Paramedics performed endotracheal intubation in one
      neonate and supported ventilation in four others. Suctioning and warming of the
      neonate were documented in 58% and 76%, respectively, and hypothermia was common
      (47%) in the paramedic-attended deliveries. There were 9 neonatal deaths. Eight
      (89%) of the neonatal deaths were in the group with no prenatal care (p <
      0.0001). Lack of prenatal care (RR 304, 95% CI = 5.0 to 18,472) and history of
      poor prenatal care (RR 22.5, 95% CI = 1.19 to 427) were significant predictors of
      poor neonatal outcome. Sixteen percent of all study patients and 43% of those
      with no prenatal care were treated in the ED during their pregnancies. Eighteen
      percent of the patients had had no prenatal care during previous pregnancies.
      CONCLUSIONS: Paramedics manage labor and delivery of a high-risk population.
      Fundamental aspects of care were not universally documented. Lack of prenatal
      care was associated with high neonatal morbidity and mortality. Nearly half of
      the mothers who went on to deliver without prenatal obstetric care saw emergency
      physicians during their pregnancies.

PMID- 10917325
TI  - Does advanced age matter in outcomes after out-of-hospital cardiac arrest in
      community-dwelling adults?
AB  - OBJECTIVE: To assess whether advanced age is an independent predictor of survival
      to hospital discharge in community-dwelling adult patients who sustained an out
      of-hospital cardiac arrest in a suburban county. METHODS: A prospective cohort
      study was conducted in a suburban county emergency medical services system of
      community-dwelling adults who had an arrest from a presumed cardiac cause and who
      received out-of-hospital resuscitative efforts from July 1989 to December 1993.
      The cohorts were defined by grouping ages by decade: 19-39, 40-49, 50-59, 60-69,
      70-79, and 80 or more. The variables measured included age, gender, witnessed
      arrest, response intervals, location of arrest, documented bystander
      cardiopulmonary resuscitation, and initial rhythms. The primary outcome was
      survival to hospital discharge. Results are reported using analysis of variance,
      chi square, and adjusted odds ratios from a logistic regression model. Age group
      50-59 served as the reference group for the regression model. RESULTS: Of the
      2,608 total presumed cardiac arrests, the overall survival rate to hospital
      discharge was 7.25%. Patients in age groups 40-49 and 50-59 experienced the best
      rate of successful resuscitation (10%). Each subsequent decade had a steady
      decline in successful outcome: 8.1% for ages 60-69; 7.1% for ages 70-79; and 3.3%
      for age 80+. In a post-hoc analysis, further separation of the older age group
      revealed a successful outcome in 3.9% of patients ages 80-89 and 1% in patients
      90 and older. Patients aged 80 years or more were more likely to arrest at home,
      were more likely to have an initial bradyasystolic rhythm, yet had a similar rate
      of resuscitation to hospital admission. In the regression model, age 80 or older
      was associated with a significantly worse survival to hospital discharge (OR =
      0.4, 95% CI = 0.20 to 0.82). CONCLUSIONS: There was a twofold decrease in
      survival following out-of-hospital cardiac arrest to discharge in patients aged
      80 or more when compared with the reference group in this suburban county
      setting. However, resuscitation for community-dwelling elders aged 65-89 is not
      futile. These data support that out-of-hospital resuscitation of elders up to age
      90 years is not associated with a universal dismal outcome.

PMID- 10917326
TI  - Wide-complex tachycardia: continued evaluation of diagnostic criteria.
AB  - OBJECTIVE: To evaluate the accuracy of the Brugada algorithm for analysis of wide
      complex tachycardia (WCT) when applied by board-certified emergency physicians
      and board-certified cardiologists. METHODS: A database consisting of 157
      electrocardiograms of WCTs were evaluated in a blinded fashion using the Brugada
      criteria to determine the presence of ventricular tachycardia (VT) or
      supraventricular tachycardia with aberrancy. These results were then compared
      with the electrophysiologically proven diagnosis for each tracing. Sensitivity
      and specificity of the Brugada criteria for diagnosis of VT were calculated. Two
      board-certified emergency physicians and two board-certified cardiologists
      analyzed each tracing, and interobserver agreement was determined using the kappa
      statistic. RESULTS: Sensitivity and specificity for the determination of VT using
      the Brugada algorithm were 85% [95% confidence interval (95% CI) = 79% to 91%]
      and 60% (95% CI = 43% to 78%) for cardiologist 1 (C 1) and 91% (95% CI = 86% to
      96%) and 55% (95% CI = 37% to 72%) for C 2. Emergency physician (EP 1) achieved a
      sensitivity of 83% (95% CI = 78% to 91%) and a specificity of 43% (95% CI = 25%
      to 59%), while EP 2 attained 79% (95% CI = 73% to 87%) and 70% (95% CI = 51% to
      84%), respectively. The original authors achieved a sensitivity of 98.7% and
      specificity of 96.5% when determining VT in their study population. Interobserver
      agreement for the emergency physicians and the cardiologists in determining VT
      was 82% and 81%, respectively. CONCLUSIONS: Neither the emergency physicians nor
      the cardiologists were able to achieve a sensitivity or specificity as high as
      that reported by the original investigators when using the Brugada algorithm to
      determine the presence of VT.

PMID- 10917328
TI  - A randomized controlled trial to assess decay in acquired knowledge among
      paramedics completing a pediatric resuscitation course.
AB  - BACKGROUND: Critical pediatric illness or injury occurs infrequently in out-of
      hospital settings, making it difficult for paramedics to maintain physical
      assessment, treatment, and procedure skills. OBJECTIVES: To document the ability
      of paramedics to retain clinical knowledge over a one-year interval after
      completing a pediatric resuscitation course and to determine whether clinical
      experience or retesting improves retention. METHODS: This was a randomized
      controlled study assessing retention of knowledge in pediatric resuscitation soon
      after, six months after, and 12 months following completion of a pediatric
      advanced life support course. Forty-three paramedics participated in pre- and
      post-pediatric resuscitation course testing and were randomly assigned to one of
      four groups. Group 1 received a knowledge examination (KE) and mock resuscitation
      scenarios (MR) at six months. Group 2 received only the KE at six months. Group 3
      received the MR only at six months. Group 4 received no intermediate testing. All
      groups were reassessed at 12 months. RESULTS: Pediatric clinical knowledge (as
      measured by KE) rose sharply immediately after the course but returned to
      baseline levels within six months. There was no difference between the groups in
      knowledge scores at 12 months, despite the interventions at six months.
      CONCLUSIONS: Although intensive out-of-hospital pediatric education enhances
      knowledge, that knowledge rapidly decays. Emergency medical services programs
      need to find novel ways to increase retention and ensure paramedic readiness.

PMID- 10917327
TI  - Pediatric emergency medicine education in emergency medicine training programs.
      SAEM Pediatric Education Training Task Force. Society for Academic Emergency
      Medicine.
AB  - BACKGROUND: The educational goal of emergency medicine (EM) programs has been to
      prepare its graduates to provide care for a diverse range of patients and
      presentations, including pediatric patients. OBJECTIVE: To evaluate the methods
      used to teach pediatric emergency medicine (PEM) to EM residents. METHODS: A
      written questionnaire was distributed to 118 EM programs. Demographic data were
      requested concerning the type of residency program, number of residents, required
      pediatric rotations, elective pediatric rotations, type of hospital and settings
      in which pediatric patients are seen, and procedures performed. Information was
      also requested on the educational methods used, proctoring EM received, and any
      formal curriculum used. RESULTS: Ninety-four percent (111/118) of the programs
      responded, with 80% of surveys completed by the residency director. Proctoring
      was primarily performed by PEM attendings and general EM attendings. Formal means
      of PEM education most often included the EM core curriculum (94%), journal club
      (95%), EM grand rounds (94%), and EM morbidity and mortality (M&M) conference
      (91%). Rotations and electives most often included the pediatric intensive care
      unit (PICU) and the emergency department (ED) (general and pediatric).
      CONCLUSIONS: Emergency medicine residents are exposed to PEM primarily by
      rotating through a general ED, the PED, and the PICU, being proctored by PEM and
      EM attendings and attending EM lectures and EM M&M conferences. Areas that may
      merit further attention for pediatric emergency training include experience in
      areas of neonatal resuscitation, pediatric M&M, and specific pediatric electives.
      This survey highlights the need to describe current educational strategies as a
      first step to assess perceived effectiveness.

PMID- 10917330
TI  - Clinicopathological conference: a previously healthy man with fever and
      pancytopenia.

PMID- 10917329
TI  - Should pediatric emergency care be decentralized?: an out-of-hospital destination
      model for critically ill children.
AB  - OBJECTIVES: A time-to-initial-stabilization model for out-of-hospital
      destinations of critically ill children (CICs) was developed. Application of this
      model to assess the impact of changes in different parameters of an emergency
      medical services for children (EMSC) system is described. METHODS: A computer
      model created a 2,500-square-mile community containing ten community hospitals
      (CHs) and one pediatric critical care center (PCC). Community hospitals capable
      of providing initial immediate stabilization of CICs were defined as emergency
      departments accepting pediatrics (EDAPs). Critically ill children were randomly
      selected in proportion to population densities across the modeled community. Time
      to initial stabilization (TIS) was defined as the time to arrival at either an
      EDAP or a PCC or time to arrival at a non-EDAP CH + travel time for a team from
      the PCC to the non-EDAP CH + preparation/dispatch (P/D) time. The following
      parameters of the model were varied and their effect on TIS was evaluated:
      location of CHs, location of PCC, primary destinations for CICs, percent of CHs
      meeting EDAP standards, out-of-hospital compliance with designated hospitals for
      CICs, P/D time, and ambulance speed. RESULTS: The computer model selected 1,000
      CICs in accordance with the population densities of the community. The scenario
      with the shortest TIS was one in which every CH achieved EDAP designation (9.8 +/
      0.5 minutes). The scenario with the longest TIS involved a model in which every
      CIC was transported directly to the PCC (28.6 +/- 0.33 minutes). The number of
      EDAPs in a community and out-of-hospital compliance with use of EDAPs produced
      comparable effects on the TIS. Travel speeds had a direct effect on TIS but also
      exaggerated inefficiencies between scenarios. The P/D time had little effect on
      the TIS. CONCLUSIONS: An out-of-hospital destination model has been developed
      with the ability to modify multiple EMSC system variables. Application of this
      model demonstrates the shortest times to stabilization of critically ill children
      occur in systems that maximize the number of hospitals that meet EDAP standards
      and decentralize pediatric emergency care.

PMID- 10917331
TI  - Pediatric emergency medicine education in emergency medicine training programs.

PMID- 10917332
TI  - State of the art: therapeutic controversies in severe acute asthma.
AB  - This is a transcript of the 1999 SAEM State-of-the-Art session on "Therapeutic
      Controversies in Severe Acute Asthma," presented at the 1999 SAEM annual meeting
      in Boston. The aim of this session was to address some of the current
      controversies in the management of acute asthma exacerbations, a major issue in
      emergency medicine. Despite many recent advances in asthma management, morbidity
      and mortality remain high. While many of us have strong feelings on how asthma
      patients should be treated, many of our assertions are not based on good science,
      and there are numerous areas of controversy. This discussion focuses on the
      controversy over beta agonist treatment for acute asthma, the physiology of
      corticosteroids in asthma, and the emergency use of leukotriene-modifying agents.

PMID- 10917333
TI  - Serum neuron-specific enolase as a predictor of intracranial lesions in children
      with head trauma: a pilot study.
AB  - OBJECTIVE: To determine the reliability of serum neuron-specific enolase (NSE)
      levels in predicting intracranial lesions (ICL) in children with blunt head
      trauma (HT). METHODS: A prospective pilot study was conducted of patients 0 to 18
      years of age presenting to a children's hospital emergency department (ED)
      between December 1997 and October 1998. Children presenting within 24 hours of
      injury who required head computed tomography (CT) were eligible. Blood samples
      were obtained to measure serum NSE level. Data collected included patient
      demographics, historical information, Glasgow Coma Scale score (GCS), physical
      examination, head CT results, and outcome. Patients were assigned to one of two
      groups based on the head CT results (PICL; presence of intracranial lesion, or
      NICL; no intracranial lesion). Data were analyzed using Student's t-test and chi
      square. The 95% confidence interval (95% CI) was calculated when appropriate. A
      receiver operating characteristic curve was constructed to determine the NSE
      level that yielded the highest sensitivity and specificity for predicting ICL.
      RESULTS: Fifty patients were enrolled; 22 (45%) had abnormal head CT. No
      difference in demographics or mechanism of injury was observed between those with
      abnormal or normal CT scans. The mean GCS level was 11.9 +/- 4.2 for PICL and
      13.9 +/- 2.6 for NICL (p = 0.045; 95% CI = -0.05 to -3.9). The mean NSE level was
      26.7 +/- 21.4 for PICL and 17.7 +/- 7.8 for NICL (p = 0.048; 95% CI = 0.1 to
      17.9). An NSE level > or = 15.3 ng/mL yielded a sensitivity of 77%, a specificity
      of 52%, and a negative predictive value of 74%. CONCLUSIONS: These results
      suggest that serum NSE may be a useful screening tool for predicting ICL in
      children with blunt head trauma. However, the NSE alone was neither sensitive nor
      specific in predicting all patients with ICL.

PMID- 10917334
TI  - Serious toxicity in a young child due to ibuprofen.
AB  - An 18-month-old male presented to the emergency department (ED) for evaluation of
      lethargy and apnea. Four hours before presentation, the patient was found with an
      empty bottle of ibuprofen, an ingestion of as much as 7.2 grams (600 mg/kg). The
      ED course was remarkable for a 30-second tonic-clonic seizure. Laboratory
      analysis was notable for metabolic acidosis. Four-hour and 7.5-hour serum
      ibuprofen levels were 640 and 39 microg/mL, respectively. Following treatment,
      the patient improved and was extubated the next morning. While metabolic acidosis
      has been frequently described at doses exceeding 400 mg/kg, seizures occurring
      early in the course of ibuprofen toxicity have been rarely noted.

PMID- 10917336
TI  - Ruptured ectopic pregnancy after elective termination of intrauterine pregnancy
      discovered by use of ultrasonography in the emergency department.
AB  - The authors report a case of a 27-year-old female who was diagnosed as having a
      ruptured ectopic pregnancy approximately 12 hours after an elective termination
      of an intrauterine pregnancy (IUP) was performed. Multiple previous evaluations
      by an obstetrician for a chief complaint of abdominal pain revealed an IUP but
      did not disclose the underlying pathology. The ectopic pregnancy was identified
      by the emergency physician's use of ultrasound in the emergency department.

PMID- 10917335
TI  - Abortifacients: toxidromes, ancient to modern--a case series and review of the
      literature.
AB  - Between 1998 and 1999, four women presented to an emergency department after
      having attempted a nonmedical abortion. All four reported turning to
      pharmacologically induced abortion because their access to health care was
      limited by lack of insurance and resources. These cases serve as a reminder that
      self-induced abortion remains a significant health problem for women, a problem
      that emergency physicians as toxicologists should be aware of.

PMID- 10917337
TI  - A comparison of two bedside tests for the detection of salicylates in urine.
AB  - OBJECTIVE: Ferric chloride (FC) and Trinder reagent (TR) have both been used to
      identify salicylates (ASA) in the urine of patients presenting with possible drug
      overdose. The authors sought to compare the sensitivities and specificities of
      these two reagents in detecting ASA in the urine of patients presenting to an
      emergency department (ED) with suspected drug overdose. METHODS: Patients were
      eligible for inclusion in this study if they presented to the ED with either
      suspected overdose or unexplained metabolic acidosis. One milliliter of the
      patient's urine was added to 1 mL of each of the two reagents. A positive test
      was defined as any darkening of the color of the reagent. Each patient had a
      quantitative serum ASA measured. RESULTS: Twenty of 180 patients (11%) had
      quantitative serum ASA levels above 5 mg/dL. Both reagents were 100% sensitive in
      identifying these patients. The specificity of FC was 71% compared with 73% for
      TR. The two reagents gave similar results in 91% of cases. CONCLUSION: Both FC
      and TR are reliable in detecting ASA in the urine of patients presenting with
      suspected drug overdose. A negative result with either test eliminates the need
      for a quantitative serum ASA level. Because FC has a longer shelf life than TR,
      it is the more practical reagent for use in the ED.

PMID- 10917338
TI  - A porcine model for instruction of lateral canthotomy.
AB  - OBJECTIVES: Retrobulbar hemorrhage is a rare condition often necessitating
      immediate lateral canthotomy for preservation of vision. It is performed
      infrequently in emergency departments (EDs); therefore, a laboratory-based
      curriculum using a swine model was developed to teach emergency medicine (EM)
      residents and pediatric emergency medicine (PEM) fellows the proper technique of
      lateral canthotomy and to provide them with hands-on training. METHODS:
      Anesthetized adult swine are used due to similarity with human anatomy and
      availability from other concurrent procedure laboratories. Fifteen to twenty
      milliliters of saline is injected behind the orbit to produce proptosis and mimic
      retrobulbar hemorrhage. A dissection is performed on one orbit to demonstrate the
      technique and to illustrate the lateral canthal ligaments. The resident then
      performs a rapid lateral canthotomy on the contralateral orbit under faculty
      supervision. RESULTS: Over one year, 19 EM residents and 3 PEM fellows were
      trained using this model. During the same period no lateral canthotomies were
      performed in the EDs. A post-laboratory survey demonstrated a high subjective
      level of comfort with this procedure. Video-based demonstration of this
      laboratory is publicly available on the World Wide Web. CONCLUSION: Adult swine
      can effectively serve as a model for resident training in lateral canthotomy, a
      rarely performed sight-saving procedure.

PMID- 10917339
TI  - Modern anesthesiologists receive limited training with ketamine--implications for
      emergency medicine.

PMID- 10917340
TI  - Misguided residency questions.

PMID- 10917341
TI  - Neuro-oncology: diagnosis and management of cerebral gliomas--past, present, and
      future.

PMID- 10917342
TI  - Modern neurosurgery for psychiatric disorders.
AB  - OBJECTIVE: The evolution, rationale, and results of modern functional
      neurosurgery to treat psychiatric disorders are documented. The potential
      benefits of neurosurgical treatment for selected, critically ill, psychiatric
      patients are considered. METHODS: The history, anatomic features, and evolution
      of and contemporary indications for the four currently used procedures
      (cingulotomy, subcaudate tractotomy, limbic leukotomy, and capsulotomy) are
      reviewed. Available outcome, neuropsychological assessment, and functional
      imaging data are presented. RESULTS: Recently, there has been a renaissance of
      interest in the surgical treatment of psychiatric disease. Modern psychiatric
      neurosurgical procedures are quite safe, with extremely low surgical mortality
      rates and transient postoperative morbidity. In selected cases, patients with
      conditions that had previously been completely refractory to comprehensive
      medical and behavioral intervention demonstrated significant improvement. This
      improvement was usually observed in the absence of long-term adverse
      neuropsychological consequences. CONCLUSION: Recent outcome studies, together
      with advances in neurobiology, psychiatry, functional imaging, and stereotaxy,
      support the further investigation of modern functional neurosurgical procedures
      to treat psychiatric disorders and their application for a subset of psychiatric
      patients with conditions refractory to all other therapies.

PMID- 10917343
TI  - Long-term visual outcome after nonradical microsurgery patients with parasellar
      and cavernous sinus meningiomas.
AB  - OBJECTIVE: To determine the long-term visual outcome in patients with parasellar
      and cavernous sinus meningiomas treated with nonradical surgery. METHODS:
      Retrospective clinical review of 29 patients with parasellar or cavernous sinus
      meningiomas and visual sensory or ocular motor dysfunction at presentation, all
      of whom had at least 10 years of follow-up after initial diagnosis and treatment
      with nonradical surgery. RESULTS: Nineteen of 29 patients had a unilateral or
      bilateral optic neuropathy at presentation, and 7 patients developed a unilateral
      or bilateral optic neuropathy during a mean follow-up period of 13.6 years.
      However, 27 (93%) of 29 patients retained vision of 20/40 or better in at least
      one eye, and 14 patients (48%) retained vision of 20/40 or better in both eyes.
      New ocular motility deficits developed in 3 (10%) of 29 patients during the
      follow-up period. CONCLUSION: Radical surgery is not required to achieve long
      term useful visual function for patients with parasellar or cavernous sinus
      meningiomas.

PMID- 10917344
TI  - Results of transsphenoidal surgery for Cushing's disease in patients with no
      histologically confirmed tumor.
AB  - OBJECTIVE: Pathological confirmation of surgical resection of an adenoma for
      Cushing's disease is not always achieved. We reviewed our experience to determine
      the prognostic significance of this lack of confirmation regarding outcome, and
      we evaluate explanations for this situation. METHODS: The records of all patients
      undergoing transsphenoidal surgery for Cushing's disease from 1992 to 1998 were
      reviewed, and those with no histological confirmation of tumor were identified.
      Information regarding preoperative and postoperative hormonal levels and clinical
      symptoms, preoperative magnetic resonance imaging data, intraoperative findings,
      and the number of reoperations were recorded. RESULTS: There were 29 patients
      with no confirmation of tumor. Nineteen (66%) of these patients were cured with
      surgery and only one had a recurrence of disease, with an average follow-up of 38
      months. An abnormality thought to represent an adenoma at the time of surgery was
      removed in 26 patients (90%). Preoperative magnetic resonance imaging suggested a
      discrete lesion in 21 patients (72%). Neither intraoperative impression nor
      magnetic resonance imaging appearance was correlated with outcome. CONCLUSION:
      Patients with no histological confirmation of tumor after transsphenoidal surgery
      for Cushing's disease are likely to have a good outcome. The results do not
      differ significantly from reported cure rates in patients with confirmed
      adenomas. Possible explanations for this situation are discussed.

PMID- 10917345
TI  - Clinical utility and cost-effectiveness of interactive image-guided craniotomy:
      clinical comparison between conventional and image-guided meningioma surgery.
AB  - OBJECTIVE: Although interactive image guidance has been determined to be an
      increasingly important and reliable tool in contemporary neurosurgery, the
      clinical results and cost-effectiveness of the use of these systems, compared
      with conventional techniques, remain understudied. The aim of this study was to
      investigate the possible benefits of image-guided craniotomies to treat
      meningiomas, in terms of hospital stays, surgical complications, and,
      consequently, cost-effectiveness, compared with the results of standard surgery
      (SS). METHODS: During a 3.5-year period, 100 patients were surgically treated for
      meningiomas using image-guided surgery (IGS) with neuronavigation assistance and
      170 were surgically treated using SS. From the consecutive series of the 100 IGS
      cases, it was possible to statistically match 50 (in terms of the demographic
      data, the location and size of the tumor, and the experience of the surgeon) with
      50 SS cases. The clinical data were collected prospectively for the IGS group and
      retrospectively for the SS group. RESULTS: The anesthetic (operation) times were
      similar for the two groups, although surgical times were shorter for the IGS
      group (P = 0.02). Blood loss during surgery was less for the IGS group (although
      not statistically significantly, P > 0.05), but more SS cases required
      transfusions (P = 0.03). The mean intensive therapy unit stay was 1.7 days for
      the SS group and 1 day for the IGS group (P = 0.12); the mean hospital stays were
      13.5 and 8.5 days, respectively (P = 0.017). Severe complications (permanent or
      requiring additional surgical procedures) were encountered in 14% of the cases in
      the SS group and 6% of the cases in the IGS group (P = 0.019), whereas the rates
      of minor complications (resolved within 30 d without further surgery) were
      similar (8 and 10%, respectively). The most common problems for the control group
      were postoperative hematomas (n = 3), which required urgent surgery in two cases;
      intractable postoperative swelling was treated by lobectomy in another case. In
      the IGS group, the two severe complications included one case of an infected bone
      flap and one case of a new permanent neurological deficit. The mean cost per
      patient was approximately 20% higher for SS than for IGS. CONCLUSION: Although
      this was not a randomized study, the analysis of these results strongly suggests
      a positive effect of neuronavigation on the complication rate and thus on
      intensive care unit and hospital stays, with attendant financial implications.

PMID- 10917346
TI  - Ommaya reservoirs for the treatment of leptomeningeal metastases.
AB  - OBJECTIVE: Ommaya reservoirs are frequently used to deliver intraventricular
      chemotherapy in cancer patients with leptomeningeal metastases. We review
      techniques of catheter placement and complication avoidance. METHODS: Between
      January 1995 and June 1998, Ommaya reservoirs were placed in 107 patients for the
      treatment or prophylaxis of leptomeningeal metastases at the Memorial Sloan
      Kettering Cancer Center. Patients with slit ventricles (total, 25) underwent
      preoperative pneumoencephalography for ventricular dilation. Intraoperative
      fluoroscopic guidance was used in 77 patients to confirm the catheter tip
      position at the foramen of Monro. Other intraoperative aids included endoscopy in
      21 patients, ultrasound in 7, and stereotaxy in 6. No aids were used in 3
      patients, more than one aid was used in 9, and the technique could not be
      determined retrospectively in 3. RESULTS: The median survival of patients treated
      for leptomeningeal metastases was 9 months (Kaplan-Meier method). Eight patients
      developed hydrocephalus requiring conversion of the Ommaya reservoir to a
      ventriculoperitoneal shunt and precluding delivery of chemotherapeutic agents. An
      additional 11 patients referred for Ommaya reservoir placement demonstrated
      elevated intracranial pressure requiring an initial ventriculoperitoneal shunt.
      Complications of Ommaya reservoir placement occurred in 10 patients (9.3%) and
      included two infections, five catheter malpositions, and three intracranial
      hemorrhages. Two deaths occurred secondary to intracranial hemorrhage: one after
      postoperative anticoagulation for a mechanical heart valve, and one attributed to
      treatment-related thrombocytopenia. Nine patients (8.4%) had treatment-related
      imaging abnormalities; seven were asymptomatic and two developed symptomatic
      leukoencephalopathy. CONCLUSION: Complications associated with Ommaya reservoirs
      can be minimized by intraoperative confirmation of the catheter position with
      fluoroscopic guidance and/or endoscopy. We recommend postoperative computed
      tomographic scans before initiation of intraventricular chemotherapy. Patients
      with elevated intracranial pressure may require shunting procedures in lieu of
      Ommaya reservoir placement.

PMID- 10917347
TI  - Surgical treatment of intracranial dural arteriovenous fistulae: role of venous
      drainage.
AB  - OBJECTIVE: This report focuses on the surgical management of aggressive
      intracranial dural arteriovenous fistulae (d-AVFs), which are defined as fistulae
      with arterialized leptomeningeal veins (red veins). Particular attention is paid
      to the accurate identification of the venous drainage pattern and to the choice
      of the proper treatment strategy. METHODS: Thirty-four consecutive patients with
      aggressive intracranial d-AVFs were treated between 1994 and 1998. Angiographic
      studies allowed the identification of two main types of aggressive lesions, i.e.,
      d-AVFs with sinus drainage and reflow into leptomeningeal veins (12 patients),
      which we designated sinus fistulae, and d-AVFs drained exclusively by
      leptomeningeal veins without sinus interposition (22 patients), which we
      designated nonsinus fistulae. All patients underwent surgical treatment, which
      consisted of resection of the fistulous sinus tract in 12 cases of sinus fistulae
      and interruption of the draining veins at their dural origin in 22 cases of
      nonsinus fistulae. Surgical preparation via multistage transarterial embolization
      was required in all 12 cases of sinus fistulae and in 4 of 22 cases of nonsinus
      fistulae. RESULTS: The mortality rate was 0%, and there were no instances of
      lasting morbidity. Radioanatomic cures were achieved in all cases. There was no
      case of venous hypertension or venous infarction after resection of the affected
      sinus or interruption of the draining veins. No arteriovenous shunts recurred
      during the follow-up period. CONCLUSION: Careful preoperative identification of
      the venous drainage pattern seems critical for planning of the correct surgical
      strategy to treat aggressive intracranial d-AVFs. If the fistula exhibits sinus
      drainage with reflow into leptomeningeal veins, surgical excision of the
      fistulous sinus segment represents a safe and definitive treatment option. In
      these cases, the affected sinus may be safely removed, provided that preoperative
      angiograms demonstrate participation of the sinus in drainage of the lesion,
      indicating that the sinus is nonfunctional. Conversely, if the fistula exhibits
      pure leptomeningeal drainage, the sinus does not participate in drainage of the
      lesion and cannot be excised. In these cases, the best treatment involves
      interruption of the draining veins at the point at which they exit the dural wall
      of the sinus. This simple easy treatment has been proven to be safe and highly
      effective in permanently eliminating arteriovenous shunts.

PMID- 10917348
TI  - Thresholds of ischemia salvageable with intravenous tissue plasminogen activator
      therapy: evaluation with cerebral blood flow single-photon emission computed
      tomographic measurements.
AB  - OBJECTIVE: This study investigated the cerebral blood flow (CBF) thresholds of
      ischemic cortices that were salvageable with intravenous tissue plasminogen
      activator (t-PA) infusion therapy. METHODS: We retrospectively reviewed data for
      20 patients who were treated with intravenous low-dose (7.2 mg) native t-PA
      infusion therapy for distal embolic occlusions of middle cerebral artery
      divisions or branches, without early computed tomographic ischemic changes. All
      patients underwent pretreatment single-photon emission computed tomographic CBF
      measurements using (99m)Tc-N,N'-(1,2-ethylenediyl)bis-L-cysteine diethylester.
      Intravenous t-PA infusion was initiated within 6 hours (average, 3 h) after
      symptom onset for 14 patients and 6 to 14 hours (average, 8.8 h) after the last
      time the patient was noted to be in normal condition for the other 6 patients.
      Pretreatment single-photon emission computed tomographic and 3-month post
      treatment computed tomographic scans were compared using computerized
      coregistration. Ischemic cortices in single-photon emission computed tomographic
      scans were divided into areas of reversible and irreversible ischemia. The degree
      of hypoperfusion was analyzed with an asymmetry index (AI). The AI was calculated
      as C(a)/C(b) x 100%, where C(a) represents the mean reconstructed counts for the
      ipsilateral ischemic area and C(b) represents the mean reconstructed counts for
      the corresponding contralateral area. RESULTS: Partial recanalization, with
      clinical improvement, at 60 minutes was confirmed by angiography for 14 of the 20
      patients (70%). Seventeen of the 20 patients (85%) exhibited major neurological
      improvements (defined as decreases in National Institutes of Health Stroke Scale
      scores of > or =4 points) at 24 hours, suggesting that recanalization occurred
      within 24 hours for almost all patients. AIs for the 25 irreversible lesions
      ranged from 15.0 to 53.4% (37.3 +/- 11.6%), whereas AIs for the 38 reversible
      lesions ranged from 45.0 to 83.1% (69.3 +/- 8.6%). There was a significant
      difference in the AIs for these two groups (P < 0.0001). The ischemia in tissue
      with AIs of more than 53.4% was reversible. In contrast, ischemic tissue with AIs
      of less than 45.0% could not escape cerebral infarction with our treatment. The
      ischemia in tissue with AIs between 45.0 and 53.4% was reversible in some
      patients and irreversible in others. CONCLUSION: To save ischemic tissue with our
      intravenous t-PA infusion therapy, residual CBF should be at least 45% of the
      contralateral presumed normal CBF value. CBF thresholds for ischemia that would
      be surely salvageable with our intravenous t-PA infusion therapy might be
      approximately 50 to 55% of the contralateral presumed normal CBF values.

PMID- 10917349
TI  - Microsurgical treatment of symptomatic sacral Tarlov cysts.
AB  - OBJECTIVE: Providing relief of symptomatic radiculopathy resulting from sacral
      perineural cysts has proven difficult. Our goal was to improve the treatment of
      these cysts with microsurgical cyst fenestration and imbrication, while
      minimizing functional damage to neural tissues. METHODS: We retrospectively
      reviewed the records for eight adult patients with large (2-3-cm) sacral
      perineural cysts who were treated at the University of California, San Francisco,
      between October 1992 and April 1999. All patients presented with radicular pain
      that was refractory to medical treatment. Three patients also reported urinary
      incontinence. We performed sacral laminectomies with microsurgical cyst
      fenestration and cyst imbrication for all patients, using intraoperative
      electromyography to minimize damage to the sacral nerve roots. For seven
      patients, we reinforced the closures with epidural fat or muscle grafts and
      fibrin glue application. For five patients with cysts that communicated with the
      subarachnoid space in computed tomographic myelograms, we placed lumbar drains
      for cerebrospinal fluid diversion for several days postoperatively. We assessed
      outcomes, using telephone questionnaires and periodic postoperative physical
      examinations, 3 to 73 months after surgery. RESULTS: After surgery, radicular
      pain improved markedly for four patients and moderately for three patients; one
      patient with initial improvement experienced pain recurrence 9 months later.
      Bladder control improved markedly for two of the three patients with bladder
      dysfunction. There were no cerebrospinal fluid leaks and no new postoperative
      neurological deficits. CONCLUSION: Microsurgical cyst fenestration and
      imbrication are effective treatments for long-term relief of refractory painful
      radiculopathy and urinary incontinence associated with large sacral perineural
      cysts.

PMID- 10917350
TI  - Neonatal ventriculosubgaleal shunts.
AB  - OBJECTIVE: We report on 32 neonates treated with ventriculosubgaleal (VSG) shunts
      to determine VSG shunt survival and associated complications. METHODS: Between
      1993 and 1997, 37 VSG shunts were placed in 32 neonates when the cerebrospinal
      fluid (CSF) or the abdomen was considered unsuitable for ventriculoperitoneal
      shunt placement. In each child, a ventricular catheter was attached to 3 cm of a
      closed-end peritoneal tube via a right-angle connector, which drained into a
      surgically created subgaleal pocket. RESULTS: The causes of hydrocephalus were as
      follows: intraventricular hemorrhage (IVH) in 20 neonates,
      meningitis/ventriculitis in 6, IVH and infection in 2, and other causes in 4. The
      mean postconception age at the time of VSG shunt insertion was 37.2 weeks (33.1
      wk in the IVH group), and the mean weight was 2227 g (1724 g in the IVH group).
      The average preoperative head circumference was 33.6 cm. The average survival of
      these 37 VSG shunts (five children had two VSG shunts) was 35.1 days. The
      complications were as follows: one CSF leakage occurred when sutures were
      removed; one catheter fell into the ventricle and required removal, and one child
      died immediately after VSG shunt revision. There were no VSG shunt infections.
      All surviving children followed for a minimum of 4 months after insertion of a
      VSG shunt (n = 24) have required a ventriculoperitoneal shunt. Mean follow-up
      from the time of first VSG shunt insertion was 21.6 months. Four children died as
      a result of causes unrelated to the VSG shunt. CONCLUSION: VSG shunts offer a
      simple, effective, and relatively safe means of temporizing hydrocephalus, and
      they avoid the need for external drainage or frequent CSF aspiration in these
      medically unstable infants until the CSF characteristics and abdomen are
      acceptable for ventriculoperitoneal shunting.

PMID- 10917351
TI  - A keyhole approach for endoscopically assisted pedicle screw fixation in lumbar
      spine instability.
AB  - OBJECTIVE: The standard approach for dorsal transpedicular fixation in lumbar
      spine instability requires extensive exposure of the vertebral column. This
      increases the risk of potential complications and possibly destabilizes healthy
      neighboring segments because of the dissection and denervation of paravertebral
      muscles. The majority of spinal disorders are currently treated successfully via
      limited and tailored approaches. Accordingly, a keyhole approach for dorsal
      fusion of the lumbar spine was developed on the basis of an anatomic study.
      METHODS: The new endoscopic technique entails the transmuscular insertion of a
      pedicle screw-rod fixation device via a rigid operating sheath. As a
      prerequisite, the endoscopic microanatomy of the target area, as visible through
      the operating sheath, was first evaluated on lumbar bone specimens. To localize
      the exact screw entry point into the pedicle, we identified the bony and
      ligamentous landmarks on partly macerated specimens. To determine the course of
      the pedicle screws, we deduced the corresponding angles of convergence from
      transparent polyester casting models of average vertebrae from T12 to S1. These
      angles were transferred into the operative situation and measured on-line with an
      inclinometer. The approach was finally tested on 12 cadavers for clinical
      feasibility and accuracy of screw placement and then successfully implemented in
      patients. RESULTS: After extracutaneous localization of the pedicles at lateral
      fluoroscopy, paramedian skin incisions were made above the pedicles of the motion
      segment to be stabilized. The operative windows were exposed by use of a rigid
      operating sheath (length, 50 mm; diameter, 15 mm), which was inserted
      transmuscularly in the pedicle axis. The screw entry point into the pedicles was
      localized by endoscopic dissection of the mamilloaccessory ligament, bridging the
      mamilloaccessory notch. The pilot holes were created via insertion of a blunt
      tipped pedicle probe. The adequate angles of convergence were constantly
      controlled during hollowing of the pedicles by an inclinometer mounted to the
      pedicle probe handle. The pedicle screws were then inserted through the operating
      sheaths. After removal of the operating sheaths, the connecting rods were
      inserted transmuscularly and anchored in the pedicle screw heads. Posterior bone
      grafting was performed after completion of the dorsal instrumentation. The dorsal
      fusion site was exposed by reinserting the operating sheath and tilting it
      medially. CONCLUSION: This new approach significantly reduces surgical
      traumatization and destabilization of adjacent motion segments. An endoscopic
      operating sheath, adopted from thoracoscopic surgery, creates space for
      visualization and surgical manipulations. The newly defined anatomic landmarks
      provide guidance to the screw entry point into the pedicle in the center of the
      exposure. Observation of the exact corresponding angles of convergence during
      screw insertion by an inclinometer facilitates correct screw placement. In
      accordance with the initial anatomic studies, this approach was successfully
      performed on 12 cadavers and then used in six patients. Two illustrative cases
      are presented.

PMID- 10917352
TI  - Motor response of the leg muscles produced by position-selective stimulation of
      spinal nerve roots.
AB  - OBJECTIVE: To define and measure motor responses of the leg muscles in the ankle
      associated with position-selective and tetanic stimulation of spinal nerve roots
      L3-S1. METHODS: Sixteen lumbosacral spinal nerve roots in 14 subjects were
      stimulated intraoperatively after surgical exposure and decompression for a
      herniated disc. Each contact of a spiral cuff multielectrode was wrapped around
      the root and used to excite a spatially defined population of axons beneath the
      electrode. The motor response from each stimulated position was evaluated in
      terms of three-dimensional vector torque in the ankle. RESULTS: Each position at
      which the stimulating electrode was placed around the root exhibited the same
      vector torque qualitatively, but at different thresholds. The root was most
      excitable ventrally. The S1 roots responded with a uniform three-dimensional
      torque pattern: plantar flexion plus lateral leg and foot rotation plus
      inversion. All L5 roots responded by plantar flexion. Dorsiflexion torque was
      possible only with stimulation of the L3 and L4 roots. Eversion was not possible
      with stimulation of the S1 roots or with most of the L5 roots. CONCLUSION:
      Position-selective stimulation of the extrathecal spinal nerve roots influences
      the threshold of the biomechanical response, the torque recruitment dynamics, and
      the magnitude of three-dimensional vector torque. Selective activation of some
      leg muscles or agonist muscle groups with stimulation of a single nerve root
      could not be achieved owing to the low spatial selectivity of the stimulation
      design and/or the low muscle specificity of motor fascicles in the root. Direct
      extrathecal stimulation of spinal nerve roots has some hypothetical advantages
      over stimulation of other sites along the peripheral nerves, owing to their
      unique anatomy, and may contribute to functional electrical stimulation of the
      lower extremities. Further investigation with a more selective multielectrode
      configuration and the use of multiple root stimulation is suggested.

PMID- 10917353
TI  - Stent-supported coil embolization: the treatment of fusiform and wide-neck
      aneurysms and pseudoaneurysms.
AB  - OBJECTIVE: We describe a consecutive series of patients treated with endovascular
      stent-supported coil embolization for symptomatic or enlarging wide-neck and
      fusiform aneurysms and pseudoaneurysms of the carotid and vertebrobasilar
      arteries. METHODS: Seven stent-supported coil embolization procedures were
      performed for seven aneurysms in seven consecutive patients. There were five
      pseudoaneurysms, one dissecting aneurysm, and one berry aneurysm. Four aneurysms
      were located in the carotid artery, and three were located in the vertebrobasilar
      system. Three aneurysms were intracranial. Four patients were symptomatic, and
      three had angiographic evidence of increasing aneurysm size. RESULTS: Technical
      success was achieved in six (86%) of seven patients. Entanglement of a coil with
      the stent struts necessitated partial coil delivery into the parent artery in one
      patient, but there were no neurological or other adverse sequelae. The 30-day
      rate of periprocedural stroke or mortality was 0%. At a mean clinical follow-up
      of 14.5 months, neurological status was at baseline or better in all patients. To
      date, all treated patients remain clinically asymptomatic with oral
      administration of aspirin only. CONCLUSION: Stent-supported coil embolization
      represents an emerging therapeutic alternative to surgery for the treatment of
      symptomatic or enlarging wide-neck and fusiform aneurysms and pseudoaneurysms of
      the cervical and vertebrobasilar arteries, which are not amenable to conventional
      unsupported coil embolization. Experience with greater numbers of patients and
      long-term follow-up are required to further validate this technique.

PMID- 10917354
TI  - Carotid balloon occlusion for large and giant aneurysms: evaluation of a new test
      occlusion protocol.
AB  - OBJECTIVE: Validation of a new angiographic test occlusion protocol before
      carotid balloon occlusion in patients with carotid aneurysms. METHODS: Carotid
      occlusion was considered for 29 consecutive patients. From 1993 to 1995, test
      occlusion in four patients consisted of clinical observation for 30 minutes and
      during electroencephalographic registration. From 1996 onward, test occlusion in
      25 patients consisted of clinical observation and angiography of collateral
      vessels. Permanent balloon occlusion was performed only when the cortical veins
      in both the occluded and the collateral vascular territories filled
      synchronously. RESULTS: Two of the four patients with normal clinical and
      electroencephalographic findings during test occlusion developed delayed
      hypoperfusion infarction after permanent carotid occlusion. Seventeen of 25
      patients (68%) demonstrated both clinical and angiographic tolerance, and no
      ischemic events occurred after permanent carotid occlusion. In one patient with
      clinical tolerance but angiographic nontolerance, permanent carotid occlusion had
      to be performed, which resulted in delayed hypoperfusion infarction. In two
      patients with angiographic nontolerance, venous filling became synchronous after
      bypass surgery. Long-term clinical follow-up showed an alleviation of the
      symptoms of mass effect in 14 of 21 patients (67%). Magnetic resonance imaging
      follow-up (range, 3-70 mo) revealed a reduction in the size of the aneurysm in 19
      of 21 patients (90%). CONCLUSION: Test occlusion with clinical and angiographic
      control is reliable, safe, and simple to perform.

PMID- 10917355
TI  - Stereotactic radiosurgery of cerebral arteriovenous malformations with a
      multileaf collimator and a single isocenter.
AB  - OBJECTIVE: To prospectively demonstrate the safety and efficacy of stereotactic
      radiosurgery for arteriovenous malformations (AVMs) of the brain with a linear
      accelerator fitted with a multileaf collimator. METHODS: A novel radiosurgery
      system was developed at the University of Michigan Medical Center with a standard
      multileaf collimator and a computer-controlled radiotherapy system. Data were
      accumulated prospectively on all patients undergoing treatment with this system
      since treatment began in 1995. RESULTS: Thirty-six patients with 37 AVMs have
      undergone treatment to date. At more than 3 years since treatment, 15 of 16 AVMs
      with a volume of less than 10 cc were proven to be obliterated by angiography or
      magnetic resonance imaging, and one was considered a treatment failure. At more
      than 24 months since therapy, all four AVMs with a volume of 10 to 25 cc were
      obliterated. Four patients with AVMs with a volume of more than 25 cc have
      undergone staged therapy, treating the entire volume to 10 Gy twice, but none has
      been followed long enough to demonstrate a final outcome. There were four
      transient and no permanent complications. CONCLUSION: Our early data indicate
      that stereotactic radiosurgery of cerebral AVMs with a linear accelerator and a
      multileaf collimator is safe and effective. Large AVMs may be especially suitable
      for this mode of therapy. Staged treatment of very large AVMs seems to be a
      promising addition to standard treatment, but longer follow-up is necessary to
      confirm that complete obliteration can be achieved.

PMID- 10917356
TI  - Advances in mobile intraoperative magnetic resonance imaging.
AB  - OBJECTIVE: The goal was to enhance a mobile magnetic resonance imaging system
      developed for neurosurgery. Components of the system included an actively
      shielded, 1.5-T superconducting magnet, a titanium operating room table, a
      radiofrequency (RF) head coil that could be disassembled, and local RF shielding.
      METHODS: The system was designed and implemented by the Division of Neurosurgery,
      University of Calgary (Calgary, Alberta, Canada), in collaboration with the
      National Research Council of Canada Institute for Biodiagnostics (Winnipeg,
      Manitoba, Canada). The ceiling-mounted, 1.5-T magnet was moved into and out of
      the surgical field as required. After initial success in monitoring the resection
      of various intracranial and cranial base lesions, significant modifications to
      the system were made by Innovative Magnetic Resonance Imaging Systems, Inc.
      (Winnipeg, Manitoba, Canada), and BrainLAB (Heimstetten, Germany). These
      modifications included the design and construction of a shorter magnet with a
      larger bore and stronger gradients, widening of the titanium operating room
      table, modification of the RF coil housing to allow vertical movement and
      incorporation of a three-pin head-clamp, construction of a transparent, copper
      impregnated RF shield, and integration with a surgical navigation system.
      RESULTS: The movable intraoperative imaging system has now been used for 101
      neurosurgical procedures, including the previously reported cases. CONCLUSION:
      The modifications to the system have enhanced its integration with established
      neurosurgical techniques and have improved patient safety. The larger magnet bore
      size, together with the ability to move the RF coil vertically, allows placement
      of patients in prone or lateral positions. Surgical navigation has been
      successfully integrated with the intraoperatively acquired high-resolution
      images. The ability to identify and resect residual lesions before wound closure
      remains a tremendous immediate advantage of this technology.

PMID- 10917357
TI  - Petroclival meningiomas: predictive parameters for transpetrosal approaches.
AB  - OBJECTIVE: To determine parameters that influence the selection of the proper
      petrosal approach or combined approaches for the excision of petroclival
      meningiomas. METHODS: We dissected 15 cadaver heads, inspected the petroclival
      region in 50 dry human skulls, and performed a retrospective analysis of the
      cases of 35 patients with petroclival meningiomas who underwent surgery via
      transpetrosal approaches. RESULTS: The petroclival region was divided into three
      "zones" based on the extent of surgical exposure achieved via the petrosal
      approaches with microscopic dissection of 15 preserved and silicone-injected
      cadaveric heads and with the measurements of 50 dry skulls. Zone I, defined as
      the area from the dorsum sellae to the internal auditory canal, is accessible via
      the anterior petrosal approach. Zone II, defined as the area from the internal
      auditory canal to the upper border of the jugular tubercle, is easily accessible
      in its lateral portion via the posterior petrosal approach. The medial portion of
      Zone II, the "central clival depression," is accessible only with cochlear
      resection and posterior facial nerve transposition. Zone III, defined as the area
      from the upper border of the jugular tubercle to the lower edge of the foramen
      magnum, is accessible via a suboccipital/transcondylar approach. The
      retrospective analysis of the cases of 35 patients who underwent transpetrosal
      resection of petroclival meningiomas between 1991 and 1998 was used to determine
      the predictive value of these anatomic parameters. The degree of tumor resection
      was analyzed with a novel grading scale combining the percentage of resection and
      the percentage of brainstem reexpansion. Total excision was achieved in 37% of
      the patients and complete brainstem reexpansion was achieved in an additional
      40%. Residual tumor was concentrated in the central clival depression in Zone II,
      as predicted by anatomic parameters, and around infiltrated neurovascular
      structures. New cranial nerve deficit occurred in 31% of the patients in the
      early postoperative period and improved to 17% at 6 months. Major morbidity
      occurred in 9% of the patients, and mortality was 0%. Early Karnofsky scores were
      reduced in 37% of the patients, but 6-month Karnofsky scores were equal to
      preoperative baseline scores or improved in 91%. CONCLUSION: Anatomic parameters
      can predict the resectability of petroclival meningiomas. Judicious application
      of cytoreductive surgery in selected patients maintains an acceptable morbidity
      and achieves adequate brainstem reexpansion.

PMID- 10917359
TI  - Topography of the vestibulocochlear nerve.
AB  - OBJECTIVE: The terms superior vestibular nerve and inferior vestibular nerve have
      been used in the field of neurosurgery to indicate anatomically the two
      respective vestibular components of the vestibulocochlear nerve. To reappraise
      the aptness of this terminology, fascicular patterns and the anatomic
      relationship of the vestibular and cochlear components were examined. METHODS:
      Twenty vestibulocochlear nerve specimens were obtained from cadavers. The nerves
      were excised, with care taken to sustain their spatial relationships, then
      embedded in paraffin blocks and cross sectioned in 10-microm-thick slices. Serial
      cross sections were stained and examined with a light microscope. RESULTS: The
      vestibular component was separated into two parts only at the lateral fundus of
      the internal auditory canal, lateral to the vestibular ganglion. In the internal
      auditory canal of all specimens, the vestibular component was represented by
      numerous fascicles. Around the porus acusticus, the fascicular pattern among the
      specimens was diverse: 13 of the 20 specimens were still polyfascicular, 4
      specimens consisted of two large, distinct fascicles, and, in the remaining 3
      specimens, a portion of the vestibular fascicles had fused with the cochlear
      component. Near the root entry zone, all vestibular fascicles fused and merged
      with the cochlear nerve to form a single trunk. CONCLUSION: There was no evidence
      to support the anatomic correctness of specifying the superior and inferior
      vestibular nerves, except in the lateral fundus of the internal auditory canal.

PMID- 10917358
TI  - Venous consideration in petrosal approach: microsurgical anatomy of the temporal
      bridging vein.
AB  - OBJECTIVE: The technical difficulty of using the petrosal approach and the
      likelihood of encountering venous complications depend on the particular temporal
      venous anatomy. To reduce such potential risks, neurosurgeons must have adequate
      knowledge of the variations in the anatomy of the temporal venous drainage
      system, particularly of the temporal bridging veins. METHODS: In 20 cadaveric
      specimens, the temporal bridging veins were examined with the aid of an operating
      microscope. The anatomic location of their termination and of the tributaries of
      these bridging veins was noted. RESULTS: Forty-four terminations and 109
      tributaries of the temporal bridging veins were identified in our specimens. The
      temporal bridging veins were divided into three groups according to the anatomic
      location of their terminations: 1) the transverse sinus group (seen in all 20
      hemispheres), with drainage into the lateral part of the cerebellar tentorium, to
      which most of the vein of Labbe belongs; 2) the tentorial group (seen in 50% of
      the 20 hemispheres), with drainage into the medial part of the tentorium, which
      is composed mainly of the middle and posterior temporobasal veins; and 3) the
      petrosal group (seen in 55% of the 20 hemispheres), with entry around the
      superior petrosal sinus, which may limit mobility of the temporal lobe in the
      petrosal approach. On the basis of this anatomic information, we propose a new
      classification of the temporal venous drainage system and discuss the clinical
      implications of these findings. CONCLUSION: In planning the petrosal approach,
      great care should be taken not only with the vein of Labbe but also with the
      petrosal bridging veins. Knowledge of this venous anatomy can reduce venous
      complications during the lateral cranial base approach.

PMID- 10917360
TI  - The neurosurgeon as innovator and entrepreneur.
AB  - INNOVATION IS THE driving force behind progress in neurosurgery. Most significant
      innovations require commercialization to ensure appropriate development and
      ultimate distribution to patients. There are several key factors that determine
      whether a particular innovation is likely to be commercially successful.
      Relationships between academic neurosurgeons and industry are likely to increase
      in the future. Stronger and more productive relationships between academic
      neurosurgeons and commercial ventures will provide new opportunities for
      neurosurgeons to bring innovations to patients more effectively and efficiently.
      The transfer of innovation from the academic environment to the commercial
      setting is consistent with the academic mission and can increase funding for
      basic and clinical neuroscience research.

PMID- 10917361
TI  - Multimedia computer database for neurosurgery.
AB  - OBJECTIVE: There is a need for an efficient mechanism of storing and analyzing
      neurosurgical clinical, imaging, and operative data to facilitate clinical audit,
      research, education, and preparation of scientific presentations. METHODS: A
      computer database was developed to meet this need. The recorded data include
      diagnoses, digitized neuroimaging studies, operative details (with intraoperative
      video clips), transcranial Doppler studies, outcomes, complications, admissions,
      and clinic visits. The anatomy, pathology, and clinical presentation are recorded
      for each diagnosis. RESULTS: The database provides an audit of neurosurgery
      cases, which includes admission Glasgow Coma Scale score, length of intensive
      care and hospital stays, Glasgow Outcome Scale score, and complications. Clinical
      research is facilitated by flexible search strategies based on the anatomy,
      pathology, or clinical presentation of diseases, or any of the recorded
      intraoperative or outcome factors. The system can be used to assess the influence
      on outcome of factors, such as transcranial Doppler velocity, intraoperative
      blood pressure, and the use of ventricular drainage, intraoperative angiography,
      or temporary clipping. The database can be used to track patients with untreated
      or partially treated conditions, such as incidental or incompletely coiled
      aneurysms. The recorded images and video clips are used for teaching and
      producing multimedia presentations and reports. The database is designed to
      enable secure Internet connections among institutions so that outcomes and
      complications can be compared among surgeons and institutions. CONCLUSION: This
      multimedia computer database facilitates clinical audit, research, teaching, and
      presentation activities.

PMID- 10917363
TI  - Unexpected neurotoxicity of etoposide phosphate administered in combination with
      other chemotherapeutic agents after blood-brain barrier modification to enhance
      delivery, using propofol for general anesthesia, in a rat model.
AB  - OBJECTIVE: Osmotic blood-brain barrier disruption (BBBD) increases brain and
      brain tumor delivery of chemotherapeutic agents, which results in increased
      efficacy against brain tumors. We previously noted that the use of propofol
      anesthesia for BBBD increased the percentage of successful disruptions, resulting
      in delivery of increased amounts of chemotherapeutic drugs. This study evaluated
      the neurotoxicity of combination chemotherapeutic administration with this
      enhanced delivery system. METHODS: Osmotic BBBD was performed in Long-Evans rats
      with isoflurane (n = 11) or propofol (n = 90) anesthesia. Carboplatin and/or
      melphalan, methotrexate, or etoposide phosphate was administered intra-arterially
      (IA) after BBBD using propofol anesthesia. Animals were assessed for systemic and
      neurological toxicity. Animals were killed for neuropathological evaluation 30
      days after treatment. RESULTS: With propofol or isoflurane anesthesia, BBBD alone
      produced no systemic or neurological toxicity. Single agents were relatively non
      neurotoxic when administered IA with BBBD, as were the combinations of
      carboplatin or melphalan with methotrexate. Etoposide phosphate in combination
      with any other agent was observed to be highly neurotoxic if both agents were
      administered after BBBD. Administration of etoposide phosphate before BBBD
      completely eliminated neurotoxicity, although acute pulmonary toxicity occurred
      with any combination of etoposide phosphate and methotrexate, regardless of the
      timing of administration. CONCLUSION: Neurotoxicity was significantly increased
      for etoposide phosphate combination groups, particularly when both drugs were
      administered IA after BBBD. This increase in neurotoxicity may reflect on
      increase in drug delivery observed with propofol anesthesia. The neurotoxicity of
      IA administered etoposide phosphate with BBBD and propofol anesthesia could be
      minimized by administering etoposide phosphate IA before BBBD and administering
      carboplatin or melphalan IA after BBBD.

PMID- 10917364
TI  - Decreased nitric oxide availability contributes to acute cerebral ischemia after
      subarachnoid hemorrhage.
AB  - OBJECTIVE: Disturbances of the L-arginine-nitric oxide (NO) vasodilatory pathway
      have been implicated as a cause of acute vasoconstriction and ischemia after
      subarachnoid hemorrhage (SAH). Because NO-dependent vasodilatory mechanisms are
      still intact in this setting, acute vasoconstriction may be the result of limited
      NO availability after SAH. The present study examines this hypothesis by
      administration of the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L
      NAME). METHODS: SAH was induced by the endovascular suture method in anesthetized
      rats. L-NAME (30 mg/kg intravenously) was injected 20 minutes before or 15, 30,
      or 60 minutes after SAH. Control rats received normal saline. Arterial and
      intracranial pressure and cerebral blood flow (CBF) were measured continuously
      for 60 minutes after SAH. RESULTS: L-NAME administration 20 minutes before SAH
      produced a significant decrease in resting CBF (29.4 +/- 3.4%; P < 0.05), but it
      had no effect on the acute decrease in CBF after SAH or on its early recovery up
      to 30 minutes after SAH. However, a significant decrease in CBF recovery was
      found in animals receiving L-NAME injections (28.7 +/- 9.4%; P < 0.05 versus
      controls) 60 minutes after SAH. Administration of L-NAME 15 or 30 minutes after
      SAH had no effect on CBF recovery, as compared with controls. However, when
      administered 60 minutes after SAH, L-NAME decreased CBF significantly (45.4 +/-
      8.8%; P < 0.05 versus controls). CONCLUSION: These results indicate a biphasic
      pattern of NO availability after SAH. NO-mediated vasodilation is limited during
      the first 30 minutes of SAH and is restored 60 minutes after SAH.

PMID- 10917362
TI  - Improved survival after boron neutron capture therapy of brain tumors by Cereport
      mediated blood-brain barrier modulation to enhance delivery of
      boronophenylalanine.
AB  - OBJECTIVE: Cereport (Alkermes, Inc., Cambridge, MA), or, as it has been
      previously called, RMP-7 (receptor-mediated permeabilizer-7), is a bradykinin
      analog that has been shown to produce a transient, pharmacologically mediated
      opening of the blood-brain barrier. The purpose of the present study was to
      determine whether the efficacy of boron neutron capture therapy (BNCT) could be
      enhanced by means of intracarotid (i.c.) infusion of Cereport, in combination
      with intravenous (i.v.) injection or i.c. infusion of boronophenylalanine (BPA)
      in the F98 rat glioma model. METHODS: For biodistribution studies, Fischer rats
      bearing intracerebral implants of the F98 glioma received i.v. or i.c. injections
      of 300 or 500 mg/kg body weight (b.w.) of BPA with or without i.c. infusion of
      1.5 microg/kg b.w. of Cereport. For therapy studies, BNCT was initiated 14 days
      after intracerebral implantation of 10(3) F98 cells. The i.v. or i.c. injection
      of BPA (500 mg/kg b.w.) was given with or without Cereport, and the animals were
      irradiated 2.5 hours later at the Brookhaven Medical Research Reactor with a
      collimated beam of thermal neutrons delivered to the head. RESULTS: At a BPA dose
      of 500 mg/kg b.w., tumor boron concentrations (mean +/- standard deviation) were
      55.7 +/- 9.6 microg/g with Cereport versus 33.6 +/- 3.9 microg/g without Cereport
      at 2.5 hours after i.c. infusion of BPA, and concentrations were 29.4 +/- 9.9
      microg/g with Cereport versus 15.4 +/- 3.5 microg/g without Cereport (P < 0.05)
      after i.v. injection of BPA. After i.c. administration of BPA and Cereport, the
      tumor-to-blood ratio was 5.4 +/- 0.6, and the tumor-to-brain ratio was 5.2 +/-
      2.4. After BNCT with BPA at a dose of 500 mg/kg, the survival time was 50 +/- 16
      days for i.c. administration of BPA with Cereport versus 40 +/- 6 days without
      Cereport (P = 0.05), 38 +/- 4 days for i.v. administration of BPA with Cereport
      versus 34 +/- 3 days without Cereport (P = 0.02), 28 +/- 5 days for irradiated
      controls, and 23 +/- 3 days for untreated controls. Compared with untreated
      controls, there was a 117% increase in lifespan in rats that received an i.c.
      infusion of Cereport and then BPA, and an 86% increase in lifespan in rats that
      received i.c. administration of BPA without Cereport. CONCLUSION: These studies
      have established that i.c. administration of Cereport can not only increase tumor
      uptake of BPA, but also enhance the efficacy of BNCT.

PMID- 10917365
TI  - First published record of a neurosurgical procedure on the North American
      continent, Mexico City, by Pedro Arias de Benavides, 1561: Secretos de Chirurgia,
      Valladolid, Spain, 1567.
AB  - The first published account of a neurosurgical intervention performed on the
      North American continent is described. The operation took place in Mexico City in
      1561. The neurosurgical intervention was performed by a Spanish surgeon, Pedro
      Arias de Benavides, on a 13-year-old boy who had sustained head trauma that
      caused an open depressed cranial fracture and exposed the cerebrum. A description
      of this case was first published in Valladolid, Spain, 6 years after the event,
      in a book entitled Secretos de Chirurgia ("Secrets of Surgery").

PMID- 10917366
TI  - Mucopolysaccharidoses and spinal cord compression: case report and review of the
      literature with implications of bone marrow transplantation.
AB  - OBJECTIVE AND IMPORTANCE: We present a patient with mucopolysaccharidosis with
      spinal cord compression, and we review previously published cases. This is the
      first published case of a patient with mucopolysaccharidosis with spinal cord
      compression who has undergone bone marrow transplantation. CLINICAL PRESENTATION:
      A 2-year-old patient with Hurler syndrome underwent bone marrow transplantation.
      Although the bone marrow transplantation improved many of the systemic effects of
      Hurler syndrome, the patient presented at 8 years of age with a cervical
      myelopathy. Magnetic resonance imaging revealed soft tissue compression of the
      upper cervical cord. The literature review demonstrates that spastic
      tetraparesis, secondary to cervical cord compression, is the most common
      presentation of this subgroup of patients. INTERVENTION: A suboccipital
      craniectomy and C1-C5 laminectomy and decompression with duraplasty were
      performed. Pathological examination of compressive soft tissue and lamina was
      consistent with mucopolysaccharidosis. Postoperatively, the patient showed
      substantial improvement in neurological function. CONCLUSION:
      Mucopolysaccharidoses can induce a compressive "metabolic myelopathy."
      Decompressive procedures have shown significant improvement in neurological
      function in the majority of patients without spinal instability. Bone marrow
      transplantation may allow more patients with mucopolysaccharidoses to survive
      long enough to require neurosurgical treatment in the future. The effect of bone
      marrow transplantation on the prevention of spinal cord compression is unclear.

PMID- 10917367
TI  - Tumoral calcinosis of the lumbar meninges: case report.
AB  - OBJECTIVE AND IMPORTANCE: Tumoral calcinosis is a rare disorder of unknown
      origin. Tumoral calcinosis involving the spine is extremely rare. This is the
      first case of tumoral calcinosis localized in the dura mater of the lumbar spine.
      CLINICAL PRESENTATION: This 55-year-old male patient presented with tumoral
      calcinosis of the lumbar meninges. T1-weighted, sagittal magnetic resonance
      imaging scans of the lumbar spine revealed a round mass of slightly increased
      intensity with high-intensity margins, located posterior to the cauda equina at
      the L4-L5 level. The cauda equina was severely compressed anteriorly. T2-weighted
      scans revealed that the mass was composed of a high-intensity area with low
      intensity margins. T1-weighted magnetic resonance imaging scans obtained after
      intravenous gadolinium administration revealed some enhancement at the margins.
      INTERVENTION: The mass lesion was totally resected. Three years after surgery, no
      recurrence was observed in follow-up magnetic resonance imaging scans.
      CONCLUSION: Although tumoral calcinosis is a rare cause of mass lesions of the
      lumbar spine, it should be considered in differential diagnoses. If the lesion
      can be totally resected, the prognosis should be good, similar to that for
      general tumoral calcinosis.

PMID- 10917368
TI  - Resolution of tonsillar herniation and syringomyelia after supratentorial tumor
      resection: case report and review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: The pathophysiological features of syringomyelia are
      not yet entirely understood. We present a case of a supratentorial mass causing
      tonsillar herniation and syringomyelia. CLINICAL PRESENTATION: A 51-year-old
      woman underwent magnetic resonance imaging for evaluation of progressive
      headaches. A large parieto-occipital mass was revealed. Herniation of the
      cerebellar tonsils and a cervical syrinx were also noted. INTERVENTION: A
      craniotomy was performed without incident. After tumor resection, the tonsils
      ascended and the syrinx resolved in a 1-year period. CONCLUSION: This case
      highlights the importance of tonsillar herniation in the pathogenesis of
      syringomyelia. "Acquired" Chiari malformations and syringomyelia attributable to
      supratentorial masses may be treated by mass resection alone, without the need
      for foramen magnum decompression.

PMID- 10917369
TI  - Delayed epistaxis resulting from external carotid artery injury requiring
      embolization: a rare complication of transsphenoidal surgery: case report.
AB  - OBJECTIVE AND IMPORTANCE: Delayed epistaxis resulting from trauma to branches of
      the external carotid artery is an infrequent but potentially serious complication
      of transsphenoidal surgery. We report two cases of severe, delayed epistaxis in
      patients who had undergone transsphenoidal surgery. In both cases, noninvasive
      treatment failed, necessitating endovascular intervention. CLINICAL PRESENTATION:
      The first patient, a 52-year-old woman with a prolactinoma, underwent a second
      transsphenoidal resection 18 months after the first surgery. She was readmitted
      on postoperative Day 15 with massive epistaxis. The second patient, a 40-year-old
      woman, had undergone two transsphenoidal surgeries, 14 years apart, for an
      adrenocorticotropic hormone-secreting adenoma. She was readmitted with massive
      epistaxis on postoperative Day 17. INTERVENTION: Both patients were initially
      treated with nasal balloon packing but experienced recurrent hemorrhage when the
      balloon was deflated, necessitating referral to the interventional radiology
      department for embolization. At arteriography, the first patient was found to
      have a pseudoaneurysm of the medial branch of the left internal maxillary artery,
      which was subsequently embolized. Arteriography in the second patient revealed an
      abnormally dilated midline branch of the right internal maxillary artery in the
      nasal septum; this vessel was occluded at arteriography. CONCLUSION: Delayed
      massive epistaxis is a rare but significant complication of transsphenoidal
      surgery. Injury to branches of the external carotid artery, along with injury to
      the internal carotid artery, should be suspected in patients who present with
      delayed epistaxis after transsphenoidal surgery. Angiography performed in
      patients with refractory bleeding should include selective external carotid
      injections. Epistaxis that is refractory to anterior and posterior nasal packing
      may be effectively treated with endovascular embolization.

PMID- 10917370
TI  - Transient cardiac standstill induced by adenosine in the management of
      intraoperative aneurysmal rupture: technical case report.
AB  - OBJECTIVE AND IMPORTANCE: Intraoperative aneurysmal rupture represents a
      potentially catastrophic event. We describe the use of an intravenous adenosine
      bolus to induce transient cardiac asystole to control a severe intraoperative
      aneurysmal rupture. This treatment resulted in a brief period of severe
      hypotension, which enabled successful clipping of the aneurysm. CLINICAL
      PRESENTATION: A 55-year-old man was referred to our institution 7 days after
      experiencing a mild subarachnoid hemorrhage from a fusiform, multilobulated
      aneurysm of the anterior communicating artery. The patient was found to have
      multiple additional fusiform aneurysms as well as a large parietal arteriovenous
      malformation. INTERVENTION: A craniotomy was performed to clip the aneurysm, but
      surgical dissection was complicated by premature rebleeding that could not be
      controlled satisfactorily with tamponade or temporary arterial occlusion.
      Infusion of adenosine resulted in the rapid onset of profound hypotension,
      allowing for safe completion of the dissection and clipping of the aneurysm with
      a good outcome. There were no complications identified in relation to the use of
      adenosine. CONCLUSION: In the setting of severe intraoperative aneurysmal
      rupture, intravenous adenosine represents a potential means of achieving a near
      immediate profound decrease in the blood pressure that may allow for safe
      completion of the dissection and aneurysm clipping.

PMID- 10917371
TI  - Rene Descartes: mind, reason, and challenging assumptions.

PMID- 10917372
TI  - A multicenter drug use surveillance of intravenous immunoglobulin utilization in
      US academic health centers.
AB  - BACKGROUND: The role of intravenous immunoglobulin (IVIG) in treating a variety
      of diseases is controversial and under active investigation for at least two
      reasons: first, a severe shortage of IVIG products exists in the US; second,
      numerous off-label (not specified in the Food and Drug Administration [FDA]
      approved label) uses for IVIG have been, and continue to be, described in the
      literature. However, most off-label uses are not supported by evidence from
      properly designed clinical trials. OBJECTIVE: To assess inpatient use of IVIG in
      a sample of US academic health centers and to compare it with published evidence
      based model guidelines for IVIG use. METHODS: Data on the use of IVIG and
      subsequent clinical outcomes in 251 patients were collected prospectively from 12
      institutions. Recommendations from consensus guidelines were used to categorize
      patients who received IVIG into one of four groups: labeled uses; off-label,
      recommended; off-label, recommended as alternative; and off-label, not
      recommended. Outcomes were scored according to guideline criteria. RESULTS: One
      hundred seven patients (43%) received IVIG for indications contained in the FDA
      approved product label, 130 patients (52%) received IVIG for off-label
      indications, and 14 (5%) received undefined treatment. Among all patients
      administered IVIG, 31 (12%) were treated for off-label recommended reasons; 64
      (26%) received off-label recommended as alternative therapy; and 35 (14%)
      received off-label not recommended therapy, as defined by model guidelines.
      Outcomes were not significantly different between the groups. CONCLUSIONS: Our
      findings suggest that IVIG continues to be used to treat a wide variety of
      conditions not specified in the product label. Furthermore, a substantial
      proportion of the reported off-label uses are not recommended according to
      evidence-based guidelines.

PMID- 10917373
TI  - Oral glutamine for the prevention of oral mucositis associated with high-dose
      paclitaxel and melphalan for autologous bone marrow transplantation.
AB  - OBJECTIVE: To determine the effect of glutamine suspension on mucositis
      associated with the administration of high-dose preparative regimens for bone
      marrow transplantation. METHODS: We performed a retrospective analysis of 21
      consecutive patients receiving high-dose paclitaxel and melphalan as the
      preparative regimen for autologous peripheral blood stem-cell transplantation for
      metastatic breast cancer between January 1997 and December 1997. Glutamine
      suspension was given as swish-and-swallow administration every four hours around
      the clock starting day-7, for a total dose of 24 g/d. RESULTS: The group given
      oral glutamine suspension demonstrated significantly fewer days of mucositis and
      a lower maximum grade of mucositis. The treatment group also had fewer days of
      parenteral morphine for pain relief. The group that did not receive glutamine
      required an average of 5.22 days of patient-controlled analgesia (PCA) morphine;
      the glutamine group did not require PCA morphine. The total days of narcotic pain
      relief were decreased in the glutamine group; however, this did not reach
      statistical significance. Qualitatively, the patients in the glutamine group had
      less oral ulceration and bleeding, and were able to tolerate liquids sooner than
      those in the nonglutamine group. Patients tolerated the glutamine suspension
      well. CONCLUSIONS: This study showed that around-the-clock administration of oral
      glutamine may decrease both the severity and duration of mucositis associated
      with high-dose bone marrow transplant preparative regimens. The decrease in
      severity and duration of mucositis translated into reduced parenteral narcotic
      use. A prospective, randomized, controlled trial is needed to determine future
      applications of glutamine in the support of patients undergoing high-dose
      chemotherapy.

PMID- 10917374
TI  - Use of rhDNase therapy and costs of respiratory-related care in patients with
      cystic fibrosis.
AB  - OBJECTIVE: To assess the relationship between level of use of recombinant
      deoxyribonuclease I (rhDNase) therapy and costs of respiratory-related care in
      patients with cystic fibrosis. DESIGN: Retrospective, cohort study using
      healthcare claims data from a large New England health insurer. PATIENTS: All
      cystic fibrosis patients five years of age and older who began therapy with
      rhDNase in 1994 (the year it was first marketed in the US). Healthcare claims
      were compiled for six months prior to first receipt of rhDNase (pretreatment) and
      for 30 months subsequently (follow-up). Patients were stratified according to
      their level of rhDNase use during follow-up, based on whether it was above or
      below the median number of therapy days for the sample. MAIN OUTCOME MEASURES:
      Costs of rhDNase, all antibiotics, and all respiratory-related outpatient
      (physician, home health, hospital outpatient) and inpatient care were included.
      All costs were expressed on an annualized basis. RESULTS: Twenty-four patients
      with cystic fibrosis who began treatment with rhDNase in 1994 met all entry
      criteria; the median number of therapy days over a 30-month period was 355. Among
      patients with low (i.e., below the median) rhDNase use (n = 12), mean +/- SD
      annualized costs of respiratory-related care increased by almost $17,000 between
      pretreatment and follow-up, from $29,251 +/- $37,919 to $46,109 +/- $40,944.
      Among high-use patients (n = 12), costs decreased by approximately $2500, from
      $37,178 +/- $48,476 to $34,592 +/- $22,591. The change in both groups was
      accounted for primarily by a change in the number of respiratory-related
      hospitalizations. CONCLUSIONS: Prolonged use of rhDNase may reduce costs of
      respiratory-related care in patients with cystic fibrosis; further study is
      required, however, to confirm these findings.

PMID- 10917376
TI  - Performance of three blood glucose meters.
AB  - OBJECTIVE: To evaluate the performance of three blood glucose meters. METHODS:
      The One Touch II (LifeScan, Milpitas, CA), Glucometer Elite (Bayer, Elkhart, IN),
      and Accu-Chek Advantage (Boehringer Mannheim, Indianapolis, IN) were compared
      with a reference laboratory method (Technicon Chem System, Tarrytown, NY). Blood
      glucose meters used in this study were validated by a clinically oriented
      approach known as the error grid analysis (EGA), for which the performance of the
      meters was compared to a laboratory standard, and by the criteria of the American
      Diabetes Association (ADA). Limits of agreement were evaluated using differences
      from the reference laboratory method and 95% Cls. Capillary blood was obtained
      from study participants in fasting state with the morning blood draw and tested
      on the three meters simultaneously. RESULTS: A total of 120 blood glucose meter
      readings were analyzed; values ranged from 62 to 396 mg/dL. For all three meters,
      at least 75% of the capillary blood glucose values fell into zone A (acceptable)
      of the EGA. The number of values falling into zone B (unacceptable) were 10, 8,
      and 6 for the Accu-Chek Advantage, the One Touch II, and the Glucometer Elite,
      respectively. Only 15-25% of the meter glucose readings met the ADA criteria of
      being within 5% of the laboratory standard. The mean difference from the
      reference values was least with the Glucometer Elite. CONCLUSIONS: The majority
      of blood glucose determinations obtained on the meters used in this study were
      within the acceptable limits using the EGA. The Glucometer Elite meter had the
      fewest values in the unacceptable range and had the least mean difference from
      reference laboratory values.

PMID- 10917375
TI  - Billing for cognitive services: understanding Quebec pharmacists' behavior.
AB  - BACKGROUND: There is growing evidence that pharmacists' interventions to solve
      drug-related problems are effective and cost-saving. Since 1978, under the Quebec
      provincial drug plan, payment for two cognitive services, the pharmaceutical
      opinion and the refusal to dispense a prescription, has been disbursed to
      community pharmacists. However, the number of claims for these services lags far
      behind expectations. OBJECTIVE: To identify factors influencing Quebec community
      pharmacists in the billing for a pharmaceutical opinion or for a refusal to
      dispense. METHODS: Questions on predisposing, enabling, and reinforcing factors
      potentially related to pharmacists' behavior were included in a self-administered
      questionnaire sent to all 3517 community pharmacists practicing in the province
      of Quebec during 1996. Using multivariate logistic regression, models were built
      to explain billing for an opinion and billing for a refusal. RESULTS: According
      to our models, the typical pharmacist who billed for opinions or refusals in
      Quebec is <45 years of age, has attended a continuing education program on this
      topic, and believes that billing for interventions is important. This typical
      pharmacist handles a mean daily volume of 100-250 prescriptions, uses a decision
      support computer program, and has sufficient technical staff assistance. This
      pharmacist believes that interventions can be billed rapidly and are consistently
      paid by the province's drug plan. CONCLUSIONS: In order to increase the billing
      of pharmaceutical care in community pharmacies, tailored educational programs
      should be offered to pharmacists. There is also a need to improve working
      conditions in pharmacies.

PMID- 10917377
TI  - Reversible granulocytopenia in association with riluzole therapy.
AB  - OBJECTIVE: To report a case of severe neutropenia developing in association with
      riluzole 200 mg/d. CASE SUMMARY: A 63-year-old woman with amyotrophic lateral
      sclerosis (ALS) presented with nausea, anorexia, and fever two weeks following
      inadvertent dose escalation of riluzole from 100 to 200 mg/d. Granulocytopenia
      was diagnosed and evaluation for a possible causative infectious process was
      negative; riluzole was considered a possible offender. Blood counts returned to
      normal with discontinuation of riluzole and administration of filgramstim.
      DISCUSSION: Riluzole is a glutamate release inhibitor used in the treatment of
      ALS, a devastating, progressive neurodegenerative disorder affecting motor
      neurons. A variety of adverse effects have been described with riluzole therapy,
      most commonly dizziness and gastrointestinal disorders. In this patient, multiple
      investigations failed to reveal an infectious cause or other drug-induced cause
      for the granulocytopenia. CONCLUSIONS: Granulocytopenia has been reported as an
      adverse effect of riluzole but is not a complication well known to clinicians,
      and there are no detailed reports published in the literature. In this patient,
      several lines of evidence raise the possibility of a causal relationship between
      riluzole and granulocytopenia.

PMID- 10917378
TI  - Warfarin and celecoxib interaction.
AB  - OBJECTIVE: To report a case of increased international normalized ratio (INR) in
      a patient receiving warfarin and celecoxib. CASE SUMMARY: A 73-year-old white
      woman with hypothyroidism and heart failure was admitted to the hospital with
      increased orthopnea, dyspnea on exertion, and hemoptysis. On laboratory
      evaluation, she was noted to have an increased INR. The only reported change in
      her medications was the addition of celecoxib approximately five weeks before
      admission. Her INR had previously been stable. After discontinuation of warfarin
      and celecoxib, fresh frozen plasma and vitamin K were administered to normalize
      INR. The patient was not rechallenged. DISCUSSION: Warfarin is an oral
      anticoagulant with numerous reports of drug interactions. It is possible that
      other drug therapies or disease states may have contributed to the elevation in
      INR; however, the observed increase in INR occurred five weeks after beginning
      celecoxib therapy. The Food and Drug Administration has issued a notice about the
      possibility of interactions between these two medications. CONCLUSIONS: Celecoxib
      may potentiate the anticoagulant effects of warfarin. Patients receiving warfarin
      should be carefully monitored when adding, changing, or removing celecoxib from
      their medication regimen.

PMID- 10917379
TI  - Doxepin toxicity in a child following topical administration.
AB  - OBJECTIVE: To describe a case of a child with altered mental status following the
      topical administration of doxepin. CASE SUMMARY: A five-year-old Hispanic girl
      was brought to the emergency department because she was difficult to arouse at
      school. She had recently developed a generalized eczematous rash for which she
      was prescribed doxepin hydrochloride 5% cream. An entire tube (30 g) of doxepin
      cream was applied in the 24 hours prior to presentation. The patient was
      responsive only to noxious stimuli, with no focal neurologic abnormalities. She
      was decontaminated and observed in a pediatric intensive care unit. By 18 hours
      after presentation, she had fully recovered and was discharged. CONCLUSIONS:
      Topical doxepin, available as a 5% cream, is indicated for the treatment of
      pruritus secondary to eczematous dermatoses in adults. Diminished skin integrity
      and the application of a massive quantity of doxepin 5% cream to a large body
      surface area contributed to the toxicity in this child. Since the safety and
      efficacy of doxepin cream has not been established in children younger than 12
      years, it should be used with caution in this population.

PMID- 10917380
TI  - Severe thrombocytopenia associated with alatrofloxacin.
AB  - OBJECTIVE: To report the development of severe thrombocytopenia during
      alatrofloxacin therapy. CASE SUMMARY: A 54-year-old Native American woman was
      admitted for pneumonia after completing a 10-day course of loracarbef 200 mg po
      bid. On admission, the woman was hypoxic (PO2 56 mm Hg) and had a platelet count
      of 408 x 10(3)/mm3. Alatrofloxacin 300 mg iv piggyback qd was initiated in the
      emergency department. The patient's condition gradually improved during the next
      three days. While preparing for discharge on hospital day 4, the patient
      developed epistaxis that lasted approximately three hours. Laboratory testing
      revealed a platelet count of 7 x 10(3)/mm3; stable red blood cell count,
      hemoglobin, and hematocrit values; and a normal white blood cell count.
      Alatrofloxacin therapy was discontinued and azithromycin was initiated on
      hospital day 4. Methylprednisolone 125 mg iv piggyback every 12 hours was
      initiated on hospital day 5. The platelet count fell to 2 x 10(3)/mm3 on hospital
      day 5 and then began to rise, reaching 60 x 10(3)/mm3 when the patient was
      discharged on hospital day 8. DISCUSSION: Numerous infectious, disease-related,
      environmental, and pharmacologic factors may cause thrombocytopenia. Drug-induced
      thrombocytopenia usually develops during the first two weeks of therapy and
      resolves within one week of drug discontinuation. Thrombocytopenia occurred in
      <1% of more than 7000 patients receiving alatrofloxacin or trovafloxacin during
      clinical trials. CONCLUSIONS: The time course of this patient's development of
      and recovery from thrombocytopenia suggests that it was induced by
      alatrofloxacin. Clinicians should monitor patients receiving alatrofloxacin or
      trovafloxacin for signs and symptoms of bleeding and thrombocytopenia.

PMID- 10917381
TI  - Hyperventilation associated with quetiapine.
AB  - OBJECTIVE: To describe a case of hyperventilation associated with the
      administration of quetiapine. CASE SUMMARY: A 69-year-old African-American woman
      admitted to a psychiatric hospital for treatment of major depression with
      psychotic features was treated and successfully discharged with quetiapine, along
      with metronidazole and miconazole to treat bacterial/monilial vaginitis. Three
      days after discharge, the patient presented to a community hospital with
      shortness of breath and hyperventilation. The patient was admitted and treated
      for tachypnea and acute respiratory alkalosis. During this hospitalization, the
      patient was noted to have increased respiratory rate following the administration
      of quetiapine. DISCUSSION: Hyperventilation was reported during the clinical
      trials of quetiapine; however, this is the first published report to date.
      Serotonin is involved both centrally and peripherally in the regulation of
      respiration. A contributing factor in this case may have been the concomitant
      administration of metronidazole, which inhibits the cytochrome P450 enzyme
      (CYP3A4) also responsible for the metabolism of quetiapine. CONCLUSIONS: The
      development of hyperventilation and respiratory alkalosis was associated with the
      administration of quetiapine.

PMID- 10917382
TI  - Inappropriate prescribing for the elderly: beers criteria-based review.
AB  - OBJECTIVE: To review currently available literature applying the Beers criteria
      for inappropriate medication use in the elderly to prescribing practices in
      various settings. DATA SOURCE: Key words including inappropriate, Beers,
      medication, prescribing, elderly, geriatric, and criteria were used to search
      MEDLINE records from January 1992 to June 1999. DATA EXTRACTION: Eight relevant
      studies were found that applied the Beers criteria in various healthcare
      settings. DATA SYNTHESIS: Each study was examined for methodologic issues,
      criteria used, prevalence, nature and extent of inappropriate medication use, and
      factors associated with their use. Despite the methodologic differences, the
      review revealed some consistent patterns across healthcare settings. This review
      has shown that: (1) most of the researchers modified the Beers criteria to
      examine inappropriate medication use in the elderly; (2) studies using patient
      based prevalence showed that between nearly one in four (23.5%) and one in seven
      (14.0%) elderly patients received an inappropriate medication as defined by
      either the Beers list of 20 inappropriate medications or the Modified Beers list;
      (3) the majority of these patients received one inappropriate agent; and (4) long
      acting benzodiazepines, dipyridamole, propoxyphene, and amitriptyline were among
      the most frequently prescribed inappropriate medications. Univariate analyses
      indicated that women, patients >80 years old, and Medicaid patients appeared to
      receive more inappropriate medications than others; however, multivariate
      analyses found that only a higher number of medications was consistently
      associated with inappropriate medication use. CONCLUSIONS: Inappropriate
      prescribing or use trends are noteworthy because they were observed despite
      methodologic differences. The findings can be instrumental in developing targeted
      interventions to influence future prescribing practices. More research is needed
      to address the national trends and healthcare impact of inappropriate drug use in
      the elderly.

PMID- 10917383
TI  - Clinical use of fluoroquinolones in children.
AB  - OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of
      fluoroquinolones in children. DATA SOURCES: A MEDLINE search (January 1966-March
      1998) was conducted for relevant literature. STUDY SELECTION AND DATA EXTRACTION:
      Data from compassionate use and published studies were reviewed for the
      assessment of pharmacokinetics, efficacy, and safety of fluoroquinolones in
      children. DATA SYNTHESIS: Fluoroquinolones have a broad spectrum coverage of gram
      positive and gram-negative bacteria, including Pseudomonas aeruginosa and
      intracellular organisms. Fluoroquinolones are well absorbed from the
      gastrointestinal tract, have excellent tissue penetration, low protein binding,
      and long elimination half-lives. These antibiotics are effective in treating
      various infections and are well tolerated in adults. However, the use of
      fluoroquinolones in children has been restricted due to potential cartilage
      damage that occurred in research with immature animals. Fluoroquinolones have
      been used in children on a compassionate basis. Ciprofloxacin is the most
      frequently used fluoroquinolone in children, most often in the treatment of
      pulmonary infection in cystic fibrosis as well as salmonellosis and shigellosis.
      Other uses include chronic suppurative otitis media, meningitis, septicemia, and
      urinary tract infection. Safety data of fluoroquinolones in children appear to be
      similar to those in adults. Fluoroquinolones are associated with tendinitis and
      reversible arthralgia in adults and children. However, direct association between
      fluoroquinolones and arthropathy remains uncertain. CONCLUSIONS: Fluoroquinolones
      have been found to be effective in treating certain infections in children.
      Additional research is needed to define the optimal dosage regimens in pediatric
      patients. Although fluoroquinolones appear to be well tolerated, further
      investigations are needed to determine the risk of arthropathy in children.
      However, their use in children should not be withheld when the benefits outweigh
      the risks.

PMID- 10917384
TI  - Recent advances in geriatrics: drug-related problems in the elderly.
AB  - OBJECTIVE: To review recent articles examining drug-related problems in the
      elderly and comment on their potential impact on geriatric pharmacy practice.
      DATA SOURCES: Six articles published in 1997 and 1998. DATA SYNTHESIS: One study
      estimated that the cost of drug-related morbidity and mortality with the services
      of consultant pharmacists was $4 billion, compared with $7.6 billion without the
      services of consultant pharmacists. A study of ambulatory elderly patients with
      polypharmacy documented that 35% reported experiencing at least one adverse drug
      event within the previous year. Another study of ambulatory elderly found that in
      those with discontinued medications, adverse drug withdrawal events were
      uncommon. Two studies, one from Canada and one from the US, describe the
      development, by consensus, of explicit criteria for defining and identifying
      inappropriate drug use in the elderly (i.e., drugs to avoid, drugs with dose
      limits, drug-drug and drug-disease interactions). Finally, a modified Delphi
      survey of an expert panel reached consensus on 18 potential risk factors for drug
      related factors in long-term care facility residents. CONCLUSIONS: Drug-related
      problems are considerable for elderly patients. Data from published studies
      should provide some guidance for today's practitioners as well as direction
      regarding future research.

PMID- 10917385
TI  - Treatment for posttraumatic stress disorder.
AB  - OBJECTIVE: To thoroughly and critically review the pharmacologic treatment of
      posttraumatic stress disorder (PTSD) and to review the symptomatology, diagnosis,
      epidemiology, pathophysiology, and assessment of PTSD. DATA SOURCES: A MEDLINE
      search (1966-October 1999) in the English language specifying PTSD drug treatment
      as the search term was used to identify articles. STUDY SELECTION AND DATA
      EXTRACTION: All articles identified were reviewed; emphasis was given to
      randomized, double-blind, placebo-controlled studies. DATA SYNTHESIS: It appears
      that a five-week medication trial is necessary to assess clinical effects on PTSD
      symptoms. The monoamine oxidase inhibitors appear to be superior to the tricyclic
      antidepressants in improving reexperiencing and avoidance symptoms. Most studies
      used assessment tools that neglected hyperarousal symptoms; therefore, no
      conclusions regarding this symptom cluster can be drawn. Other
      pharmacotherapeutic interventions reported in open-label trials have yielded
      varying success. CONCLUSIONS: The current literature does not bear a sufficient
      number of double-blind, placebo-controlled studies using assessment tools that
      evaluate the three symptom clusters of PTSD to allow for a definite treatment
      modality to be formulated. Nonetheless, a treatment hierarchy appears to be in
      order based on the greatest number of double-blind, placebo-controlled studies
      evaluating antidepressants. Alternate modalities such as mood stabilizers,
      antipsychotics, anxiolytics, and adrenergic blockers should not be considered the
      mainstays of therapy.

PMID- 10917386
TI  - Tacrolimus: an alternative for graft-versus-host disease prevention.
AB  - OBJECTIVE: To evaluate the efficacy of tacrolimus for prevention of graft-versus
      host disease (GVHD) in patients receiving allogeneic bone marrow transplants.
      DATA SOURCES: Published literature was identified through MEDLINE (January 1990
      December 1998) using the key words tacrolimus, FK506, graft-versus-host disease,
      and bone marrow transplant. DATA SYNTHESIS: GVHD associated with allogeneic bone
      marrow transplant is a serious life-threatening complication. An evaluation of
      studies using tacrolimus for prevention of GVHD was conducted. CONCLUSIONS:
      Tacrolimus is effective for the prevention of GVHD in allogeneic bone marrow
      transplant. Further studies need to be conducted to optimize the dosage schedule
      and to determine therapeutic ranges, efficacy, and safety.

PMID- 10917387
TI  - Levodopa therapy and the risk of malignant melanoma.
AB  - OBJECTIVE: To evaluate the use of levodopa therapy in patients with Parkinson's
      disease and malignant melanoma. DATA SOURCES: A MEDLINE search (January 1966
      September 1999) of English-language articles was conducted. Key search terms
      included levodopa, melanoma, and Parkinson's disease; 34 case reports were
      identified. DATA SYNTHESIS: Carbidopa/levodopa continues to be a mainstay in the
      treatment of Parkinson's disease. Since the late 1970s, a warning has appeared in
      the prescribing literature for levodopa regarding the risk of activating
      malignant melanoma. An evaluation was conducted of the case reports in which a
      causal relationship between levodopa and melanoma was suggested. CONCLUSIONS:
      There is an unlikely association between levodopa and induction or exacerbation
      of malignant melanoma.

PMID- 10917388
TI  - Aerosolized furosemide in the treatment of acute respiratory distress and
      possible bronchopulmonary dysplasia in preterm neonates.
AB  - OBJECTIVE: To review the efficacy and safety of inhaled furosemide in the
      treatment of acute respiratory distress and possible bronchopulmonary dysplasia
      (BPD) in preterm neonates receiving ventilator and oxygen support. DATA SOURCES:
      A MEDLINE search was performed from January 1966 to December 1998 using the key
      words inhaled or aerosolized furosemide, BPD, preterm, neonate, and infant
      newborn. STUDY SELECTION AND DATA EXTRACTION: All clinical trials involving the
      use of inhaled furosemide in ventilator- and oxygen-dependent preterm neonates
      with acute respiratory distress and possible BPD were evaluated. DATA SYNTHESIS:
      Inhaled furosemide 1 and 2 mg/kg has improved pulmonary function in preterm
      neonates without significant adverse effects. However, only a single dose of
      inhaled furosemide was used in these trials, and pulmonary functions were
      monitored for only two or four hours after administration. CONCLUSIONS: Inhaled
      furosemide may be effective, but studies are needed to determine the optimal
      dosage regimen and long-term risks and benefits of its use in these patients.

PMID- 10917389
TI  - Relationship between clinical and biologic variables and chloramphenicol
      pharmacokinetic parameters in pediatric patients with sepsis.
AB  - OBJECTIVE: To evaluate the influence of several clinical and biologic factors on
      the disposition kinetics of oral chloramphenicol in pediatric patients and to
      determine the usefulness of this information to predict chloramphenicol serum
      concentrations. STUDY DESIGN: The clinical, biologic, and pharmacokinetic data of
      30 consecutive pediatric patients diagnosed with sepsis and admitted to a
      tertiary care center were analyzed retrospectively. The patients were randomly
      assigned to a study group and a validation group. The model was developed by a
      three-step approach involving Bayesian estimation of pharmacokinetic parameters,
      selection of covariates by principal component analysis, and final selection by
      stepwise multiple linear regression. The model was tested in the study group and
      compared with a general population model using a prediction error analysis.
      RESULTS: Regression analysis revealed that weight, albumin, and white blood cell
      (WBC) count were the most important determinants for chloramphenicol distribution
      volume, whereas age, WBC count, and serum creatinine were the most important
      determinants for chloramphenicol clearance. The performance of the constructed
      population model improved significantly in terms of both bias and precision
      compared with the general model when tested in the validation group. CONCLUSIONS:
      Clinical and biologic factors may significantly influence chloramphenicol's
      disposition in pediatric patients with sepsis and therefore should be considered
      in programming dosage regimens.

PMID- 10917390
TI  - Performing and billing for cognitive services: implications for the US.

PMID- 10917391
TI  - Indinavir crystalluria in an HIV-positive man.

PMID- 10917392
TI  - Lessons from the fenfluramines: antiobesity medications are frequently misused.

PMID- 10917393
TI  - Thrombotic thrombocytopenic purpura induced by ticlopidine: the power of "dear
      health professional" letters.

PMID- 10917394
TI  - Atrial fibrillation following acute overdose with oral cyclosporine.

PMID- 10917397
TI  - Recommended childhood immunization schedule--US, 2000.

PMID- 10917395
TI  - Methadone withdrawal symptoms with nevirapine and efavirenz.

PMID- 10917396
TI  - Product monographs supplied by drug manufacturers to community pharmacists in
      Spain.

PMID- 10917398
TI  - More on oral contraceptives, drug interactions, herbal medicines, and hormone
      replacement therapy.

PMID- 10917399
TI  - Olanzapine-exposed pregnancies and lactation: early experience.
AB  - Psychosis frequently occurs in women of childbearing potential who may have
      unplanned pregnancies. Understanding the risk of prenatal antipsychotic exposure
      can be of benefit in selecting therapies. The authors evaluated the in utero and
      lactation exposure effects of olanzapine, a novel antipsychotic that is used in
      treating schizophrenia, bipolar disorder, and other conditions and that may have
      expanded use in the childbearing population. All prospectively and
      retrospectively ascertained pregnancy reports were collected as a registry in the
      Lilly Worldwide Pharmacovigilance Safety Database. Outcomes were available from
      23 prospectively ascertained olanzapine-exposed pregnancies. Spontaneous abortion
      occurred in 13%, stillbirth in 5%, major malformation in 0%, and prematurity in
      5%, all within the range of normal historic control rates. There were 11
      retrospectively ascertained cases of pregnancy. Two retrospectively ascertained
      cases of lactation exposure did not suggest infant risk. The early experience
      with olanzapine use in pregnancy and lactation is encouraging in that no obvious
      added risk to the fetus or infant was observed. Additional cases of pregnancy and
      lactation exposure need to be evaluated to determine whether these early findings
      are representative of the risks of olanzapine exposure to the fetus and infant.
      At this time, olanzapine should only be used during pregnancy and lactation when
      the potential benefit justifies the potential risk to the fetus or infant.

PMID- 10917400
TI  - Therapeutic spectrum of nemonapride and its relationship with plasma
      concentrations of the drug and prolactin.
AB  - The therapeutic spectrum of nemonapride, a new substituted benzamide, and its
      relationship with plasma concentrations of the drug and prolactin were
      investigated by a fixed-dose study (18 mg/day for 3 weeks) in 31 patients with
      acutely exacerbated schizophrenia. Of 31 patients, 25 (80.6%) were responders who
      showed a reduction in symptoms (percentage of improvement) of 50% or more after 3
      weeks. The mean values of percentage of improvement in scores on the total Brief
      Psychiatric Rating Scale (BPRS) and the five subscale symptoms were 71.5% for
      total, 73.2% for Positive, 86.0% for Excitement, 53.9% for Negative, 84.2% for
      Cognitive, and 67.5% for Anxiety-Depression. Responders had higher percentage of
      improvement in positive (84.6 +/- 17.0% vs. 25.9 +/- 15.7%; p < 0.001) and
      anxiety-depression (76.9 +/- 18.8% vs. 28.5 +/- 39.9%; p < 0.005) symptoms than
      did nonresponders after 3 weeks. The percentage of improvement in total BPRS
      after 2 weeks was well correlated with that after 3 weeks (Spearman rank
      correlation coefficient: r(s) = 0.711; p < 0.01). There was an inverted U-shaped
      relationship between plasma drug concentrations (nemonapride plus
      desmethylnemonapride) and percentage of improvement in total BPRS symptoms after
      a 3-week treatment (y = 46.9 + 73.9x - 44.2x2; p < 0.001). These findings suggest
      that nemonapride has a broad therapeutic spectrum in the treatment of acute
      schizophrenia. The improvements in scores for the Positive and Anxiety-Depression
      subscale symptoms are regarded as determinant factors for total response to
      nemonapride. An assessment of clinical status after 2 weeks and plasma drug
      monitoring may be useful for the prediction of the final outcome for patients.

PMID- 10917401
TI  - Obsessive and compulsive symptoms in schizophrenia: a randomized controlled trial
      with fluvoxamine and neuroleptics.
AB  - Obsessive-compulsive-related disorders are frequently comorbid with
      schizophrenia. The existence of obsessive and compulsive symptoms in patients
      with schizophrenia represents one of the most severe types of psychotic disorders
      and may predict a poor prognosis in most cases. Previous pilot studies and case
      reports have shown that the condition of some patients with schizophrenia did not
      exacerbate and even improved when serotonin reuptake inhibitors (SSRIs) were
      added to their standard neuroleptic regimen. The aim of this study was to
      evaluate the efficacy of a combination treatment of an SSRI (fluvoxamine) and
      standard neuroleptics for the treatment of obsessive-compulsive (OC)
      symptomatology in patients with schizophrenia compared with administration of
      neuroleptics only. Thirty inpatients who met DSM-IV criteria for schizophrenia
      and also had prominent OC symptoms were randomly divided into two groups.
      Fourteen patients were treated with conventional neuroleptics and fluvoxamine in
      doses of 100 to 200 mg/day for 8 weeks. Sixteen patients comprised a control
      group and received only their previous therapeutic neuroleptic therapy. The
      patients were assessed using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS),
      the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global
      Impression Scale (CGI) at baseline and endpoint. Side effects were assessed
      weekly. The data were analyzed using an analysis of variance. A considerable
      reduction in PANSS (34.3%) and Y-BOCS (29.4%) scores was noted, and CGI scores
      decreased moderately in both groups. None of the patients showed an acute
      exacerbation at the end of the study. Side effects were mild and easily tolerated
      in most patients. This open, randomized, controlled study reveals that
      coadministration of fluvoxamine, an SSRI, and neuroleptics in patients with
      schizophrenia and OC symptoms was associated with specific improvements of these
      symptoms. Thus, the use of an SSRI in treating a patient with schizophrenia and
      OC symptomatology may be warranted and safe. Other implications of the findings,
      including general safety of the combined pharmacotherapy and the use of new
      antipsychotic medications, are also discussed.

PMID- 10917402
TI  - Intravenous versus oral administration of amitriptyline in patients with major
      depression.
AB  - Antidepressants can be administered by different routes. Advantages for either
      the oral or the intravenous administration have been suggested from
      pharmacokinetic as well as from clinical points of view. Controlled comparison
      studies of the two routes do not provide unequivocal recommendations. In this
      investigation, amitriptyline was studied over a 4-week period consisting of a 2
      week, double-blind/double-dummy phase with either oral (150 mg/day), high-dose
      intravenous (150 mg/day), or medium-dose intravenous (100 mg/day) treatment and a
      2-week phase of open oral treatment in 80 patients with major depression. A
      psychopathologic assessment was made using the Hamilton Rating Scale for
      Depression, the Clinical Global Impressions Scale, the von Zerssen's
      "Befindlichkeitsskala," an adjective checklist, and a Visual Analog Scale. No
      significant differences were found concerning the mean scores of the rating
      scales or time of onset of action in the physicians' ratings. In the patients'
      self-ratings, there was an earlier therapeutic effect in the high-dose
      intravenous group. The number of improvers after 7 days was significantly higher
      in the high-dose intravenous group compared with both other groups. After 14
      days, no significant differences in the numbers of improvers and responders
      between groups were detected. The results of this study do not clearly favor one
      of the tested options. The main differences found in this study seem to be dose
      related rather than differentiating between oral and intravenous routes of
      administration.

PMID- 10917403
TI  - Weekly dosing of fluoxetine for the continuation phase of treatment of major
      depression: results of a placebo-controlled, randomized clinical trial.
AB  - Fluoxetine (FLX) has a unique pharmacokinetic profile. Its major metabolite,
      norfluoxetine (NFLX), possesses FLX's antidepressant efficacy and a half-life of
      7 to 15 days, suggesting the possibility of nonstandard dosing strategies. This
      study examined the tolerability of a weekly dose and its equivalence to daily
      dosing of FLX for the continuation phase of treatment for major depressive
      disorder (MDD). One hundred fourteen subjects initially received open-label
      treatment with 20 mg of FLX daily for 7 weeks. Subsequently, 70 subjects with a
      score on the Hamilton Rating Scale for Depression (HAM-D) of 12 or less were
      randomly assigned in a double-blind design to one of three treatment groups: 20
      mg FLX daily (N = 21), 60 mg FLX weekly (N = 28), or placebo (N = 21) and were
      followed for 7 weeks. HAM-D scores and blood levels of FLX and NFLX were analyzed
      using a repeated-measures analysis of variance. During the double-blind phase,
      blood levels for both FLX and NFLX differed across the treatment groups, yet no
      statistically significant difference in HAM-D scores was observed. There was no
      difference in the dropout rate across the groups. Subjects could not correctly
      identify the treatment group into which they were assigned. Weekly dosing of FLX
      seems to be well tolerated and possibly as effective as daily dosing in
      maintaining the therapeutic response in subjects with MDD.

PMID- 10917404
TI  - Effect of selective serotonin reuptake inhibitors on the oxidative metabolism of
      propafenone: in vitro studies using human liver microsomes.
AB  - Propafenone is mainly metabolized by CYP2D6 to form 5-hydroxypropafenone (5-OHP)
      and to a minor extent by CYP1A2 and CYP3A4 to form N-depropylpropafenone (N-DPP).
      The in vitro inhibitory effect of selective serotonin reuptake inhibitors (SSRIs)
      on the formation of both metabolites was studied, using human liver microsomes.
      The 5-OHP formation from racemic propafenone and from its individual enantiomers
      followed one-enzyme Michaelis-Menten kinetics. Incubation with the racemate
      yielded a mean Vmax of 64 pmol x min(-1) x mg(-1) and a mean Km of 0.12 microM (N
      = 3). Stereoselectivity in Vmax and Km values was observed, with (S)-propafenone
      displaying higher Km and Vmax values. N-DPP formation from racemic propafenone
      followed one-enzyme Michaelis-Menten kinetics and yielded a mean Vmax of 403 pmol
      x min(-1) x mg(-1) and a mean Km of 116 microM (N = 3). No stereoselectivity in
      propafenone N-dealkylation was observed. The influence of SSRIs and quinidine, a
      prototypical CYP2D6 inhbitor, on propafenone 5-hydroxylation was investigated.
      Quinidine was the most potent inhibitor, followed by fluoxetine, norfluoxetine,
      and paroxetine. Sertraline, desmethylsertraline, and fluvoxamine had only a
      moderate inhibitory effect, whereas citalopram displayed slight or no inhibition
      when racemic propafenone was used as substrate. Mean Ki values of quinidine,
      fluoxetine, norfluoxetine, and paroxetine were 0.13, 0.33, 0.55, and 0.54 microM,
      respectively (N = 3). Quinidine and paroxetine were also tested as inhibitors
      using the individual enantiomers, but no stereoselectivity was observed. Among
      the SSRIs tested, only fluvoxamine substantially inhbited propafenone N
      dealkylation with a mean IC50 of 7.0 microM (N = 3). There was a more pronounced
      inhibitory effect of fluvoxamine on (R)-propafenone than on (S)-propafenone N
      dealkylation. In conclusion, these in vitro data suggest that an in vivo
      interaction between propafenone and the SSRIs, fluoxetine and paroxetine, can be
      expected, which can lead to clinically relevant beta-blockade and an increased
      risk of side effects in the central nervous system. An interaction with
      fluvoxamine may be of importance in poor metabolizers for CYP2D6.

PMID- 10917405
TI  - Inhibition of cytochrome P450 2D6 modifies codeine abuse liability.
AB  - Oral codeine preparations, widely used for analgesia and cough suppression, are
      abused by some individuals for their mood-altering properties. The enzymatic O
      demethylation of codeine is catalyzed by cytochrome P450 2D6 (CYP2D6), leading to
      the production of metabolites (morphine, morphine-6-glucuronide) that are
      pharmacologically more potent than codeine. A placebo-controlled, single-blind
      study was conducted to characterize the subjective effects of codeine associated
      with abuse liability and to determine the importance of metabolic O-demethylation
      to codeine abuse liability. Twelve non-drug-dependent subjects received oral
      administration of placebo and codeine 60, 120, and 180 mg, and a favorite dose
      (FD) was determined for each subject. The FD was readministered after
      pretreatment with placebo, 50 mg of quinidine (a specific, selective CYP2D6
      inhibitor) once, or 50 mg of quinidine given four times a day for 4 days. Single
      dose quinidine pretreatment significantly decreased the recovery of O
      demethylated metabolites in plasma (p < 0.01) and resulted in a decrease in the
      positive (e.g., "high," p < 0.05) and negative (e.g., nausea, p < 0.05)
      subjective effects of codeine in both the FD120 and FD180 groups. Short-term
      quinidine pretreatment inhibited codeine O-demethylation more than did single
      dose quinidine pretreatment (p < 0.01), and it decreased positive codeine effects
      in the FD120 group (N = 7), but unexpectedly not in the FD180 group (N = 5).
      These results suggest that the O-demethylated metabolites contribute
      substantially to the subjective effects and abuse liability of codeine.

PMID- 10917406
TI  - Event-related brain potentials and working memory function in healthy humans
      after single-dose and prolonged intranasal administration of adrenocorticotropin
      4-10 and desacetyl-alpha-melanocyte stimulating hormone.
AB  - Neuropeptides of the adrenocorticotropin/melanocorticotropin (ACTH/MSH) family
      are most potent modulators of cognitive function. Their neurobehavioral activity
      is principally encoded in the 4-10 fragment of the ACTH/MSH molecule; in humans,
      it has been shown to pertain primarily to functions of attentive
      stimulus/response processing. The aims of this study were (1) to examine the
      effects of ACTH 4-10 on event-related brain potentials (ERPs) and behavioral
      indicators of stimulus encoding within the working memory; (2) to compare the
      effects after a single dose and after prolonged treatment with ACTH 4-10; and (3)
      to compare the effects of ACTH 4-10 with those of desacetyl-alpha-MSH (i.e., ACTH
      1-13 amide), which, like ACTH 4-10, binds to the known brain melanocortin
      receptors (MC-Rs) but with distinctly higher affinity. Double-blind, placebo
      controlled experiments were performed in 60 healthy control subjects. The authors
      monitored ERPs and reaction times while these subjects performed an auditory
      vigilance task ("oddball"). Recall was tested on a verbal short-term memory task
      including different word categories (neutral, rare, food, sex). After a single (1
      mg) as well as prolonged intranasal administration (1 mg/day over a period of 6
      weeks), ACTH 4-10 enhanced the positive slow wave in ERPs to target stimuli of
      the vigilance task (p < 0.05), but left classic P3 unaffected. Moreover, single
      dose and prolonged administration of ACTH 4-10 increased the rate of false
      responses during vigilance (p < 0.01). In the short term, ACTH 4-10 also impaired
      recall of neutral words (p < 0.05). Equimolar doses of desacetyl-alpha-MSH did
      not influence ERPs, neither after a single dose nor after prolonged treatment.
      Similar to ACTH 4-10, desacetyl-alpha-MSH increased the error rate during
      vigilance and acutely impaired the recall of neutral words. The increase in ERP
      slow-wave positivity, in conjunction with behavioral impairments after treatment
      with ACTH 4-10, complemented previous results of inferior focusing of attention
      and a less concise structure of thought after administration of ACTH 4-10. The
      changes indicated an impairment in differential processing of relevant versus
      irrelevant contents within the working memory, and, in this regard, might mimic
      aspects of psychopathologic disturbances of attention and thought processes.
      Their persistence after prolonged treatment with ACTH 4-10 suggests an activation
      of mechanisms subserving the consolidation of the peptide's effects. The poor
      efficacy of desacetyl-alpha-MSH suggests that the known MC-Rs may be irrelevant
      for mediating cognitive effects of this neuropeptide family.

PMID- 10917407
TI  - Human pharmacology of 3,4-methylenedioxymethamphetamine ("ecstasy"): psychomotor
      performance and subjective effects.
AB  - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug of
      increasing use among youth because of its apparent entactogenic properties, such
      as euphoria, friendliness, closeness, and empathy. However, experimental studies
      have shown MDMA to be neurotoxic. Data on pharmacologic actions of MDMA in humans
      are limited. The authors conducted a randomized, double-blind, crossover,
      controlled trial to assess psychomotor performance and subjective effects in
      eight healthy male volunteers. MDMA was given in the same range of doses used for
      recreational purposes (75 and 125 mg). Amphetamine (40 mg) and placebo were used
      as reference compounds. For the digit-symbol substitution test (DSST), MDMA-125
      produced a mild decrease in responses, and amphetamine produced a mild
      improvement. For the Maddox wing device, MDMA-125 induced esophoria compared with
      the other drug conditions. MDMA-125 and MDMA-75 produced increases in feelings of
      euphoria and well-being, as noted by increases in scores on the Addiction
      Research Center Inventory (ARCI) MBG and A scales, as well as scores of
      "stimulated," "good effects," "liking," and "high" on the visual analog scales.
      Amphetamine administration induced similar effects. At the same time, MDMA-125
      enhanced sedation- and dysphoria-related effects (ARCI-PCAG and LSD, "confusion,"
      "drunken," and Profile of Mood States Confusion scale). Mild changes in some body
      perception-related feelings were also reported after MDMA use, but hallucinations
      or psychoses were not present. In summary, the short-term administration of MDMA
      produced marked euphoria, a slight impairment in the performance of psychomotor
      tasks, and mild changes in body perceptions without hallucinations. These data
      support the abuse liability of MDMA.

PMID- 10917409
TI  - Specific sensory detection, discrimination, and hedonic estimation of nicotine
      enantiomers in smokers and nonsmokers: are there limitations in replacing the
      sensory components of nicotine?
AB  - The aim of this study was to investigate in smokers and nonsmokers (1) the
      olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the
      discrimination ability and hedonic estimation of nicotine enantiomers in
      olfactory and trigeminal concentrations. Thirty healthy male subjects (15
      smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of
      R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli)
      were introduced into the right nostril of the subjects using a Kobal
      olfactometer. The subjects were instructed to group the stimuli into two
      categories (A and B). To test the role of the olfactory and the trigeminal system
      in this discrimination task, the authors studied the olfactory detection
      threshold for the "odorous" sensation and the trigeminal detection thresholds for
      the "burning" and "stinging" sensations. Nicotine enantiomers were presented at
      the individual "olfactory" and "trigeminal" concentration levels. The subjects
      estimated the hedonic properties using a bipolar visual analog scale (from "very
      unpleasant" to "very pleasant"). A statistical evaluation (t-test) revealed that
      the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and
      trigeminal concentrations (p < or = 0.01, p < or = 0.001, respectively). At
      concentrations near the detection thresholds, i.e., clearly below subjective pain
      thresholds, smokers rated both nicotine stereoisomers to be significantly more
      pleasant than did nonsmokers (t-test, R(+)-nicotine: p < or = 0.05; S(-)
      nicotine: p < or = 0.01). Increasing the concentrations to above trigeminal
      thresholds resulted in a difference in hedonic estimates. Smokers perceived the
      S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations
      (t-test, p < or = 0.001). This difference in perception might be explained by the
      smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer
      in tobacco.

PMID- 10917408
TI  - Placebo-controlled study of gabapentin treatment of panic disorder.
AB  - A randomized, double-blind, placebo-controlled, parallel-group study was
      conducted to evaluate the efficacy and safety of gabapentin in relieving the
      symptoms of panic disorder. One hundred three patients were randomly assigned to
      receive double-blind treatment with either gabapentin (dosed flexibly between 600
      and 3,600 mg/day) or placebo for 8 weeks. No overall drug/placebo difference was
      observed in scores on the Panic and Agoraphobia Scale (PAS) (p = 0.606). A post
      hoc analysis was used to evaluate the more severely ill patients as defined by
      the primary outcome measure (PAS score > or = 20). In this population, the
      gabapentin-treated patients showed significant improvement in the PAS change
      score (p = 0.04). In patients with a PAS score of 20 or greater, women showed a
      greater response than men regardless of treatment. Adverse events were consistent
      with the known side effect profile of gabapentin and included somnolence,
      headache, and dizziness. One patient experienced a serious adverse event during
      the study. No deaths were reported. The results of this study suggest that
      gabapentin may have anxiolytic effects in more severely ill patients with panic
      disorder.

PMID- 10917410
TI  - Risperidone for the treatment of stuttering.
AB  - A randomized, double-blind, placebo-controlled study was conducted to assess the
      efficacy of risperidone in the treatment of developmental stuttering in 16
      adults. Eight subjects received placebo and eight received risperidone at 0.5 mg
      once daily at night, increased to a maximum of 2 mg/day. After 6 weeks of
      treatment, decreases in all measures of stuttering severity were greater in the
      risperidone group than in the placebo group; the between-treatment difference was
      significant (p < 0.05) on the most important measure, the percentage of syllables
      stuttered. In the risperidone group, reductions from baseline in scores for the
      percentage of syllables stuttered, time stuttering as a percentage of total time
      speaking, and overall stuttering severity were significant (p < 0.01); changes in
      scores on the fourth measure of stuttering, duration, were not significant. No
      significant decreases occurred in the placebo group. Among the eight patients in
      the risperidone group, five responded best to 0.5 mg/day, with stuttering
      recurring at higher doses. The remaining three patients responded better with
      increasing doses of risperidone. Risperidone was generally well tolerated. The
      results of this small study indicate that risperidone may be effective in the
      treatment of developmental stuttering. This finding needs to be confirmed in a
      larger trial.

PMID- 10917411
TI  - Efficacy of venlafaxine and predictors of response in a prospective open-label
      study of patients with treatment-resistant major depression.
AB  - The aim of this study was to replicate the findings of a 1994 study, in which a
      30% response rate to venlafaxine was found in patients with treatment-refractory
      depression, as well as to examine for any predictors of such an outcome. The
      study was an 8-week, open-label, prospective investigation of venlafaxine in
      doses up to 300 mg in 312 patients fulfilling criteria for either "absolute" or
      "relative" treatment resistance. By week 8, 52.6% of the patients had responded,
      which was defined as a 50% reduction in scores on the Montgomery-Asberg
      Depression Rating Scale; 49% of those defined with "absolute resistance"
      demonstrated such an outcome. Forty-five percent of the patients with absolute
      resistance who had failed to respond to at least one tricyclic antidepressant
      responded to venlafaxine. Response rates were higher in those with an absence
      (57.5%) compared with the presence (31.0%) of any comorbid psychiatric disorder
      (p < 0.001), "marked" (60.3%) compared with "mild or moderate" (51.6%) or
      "severe" (43.4%) baseline ratings on the patient-rated Clinical Global
      Impressions Scale (p < 0.05), and "relative" (61%) compared with "absolute"
      resistance (49%) (p = 0.06). Furthermore, improvement in scores of 20% or 30% at
      weeks 1 or 2 was associated with higher rates of final response (p < 0.0005).
      After logistic regression, both comorbid psychiatric illness (p < 0.001) and
      early improvement (p < 0.0001) remained significant and independent predictors of
      final response.

PMID- 10917412
TI  - Esotropia associated with olanzapine.

PMID- 10917413
TI  - Case report of withdrawal syndrome after olanzapine discontinuation.

PMID- 10917414
TI  - Agranulocytosis during treatment with mianserin and venlafaxine.

PMID- 10917415
TI  - Fluvoxamine concentrations in breast milk and in maternal and infant sera.

PMID- 10917416
TI  - Increase in serum clomipramine concentrations caused by valproate.

PMID- 10917417
TI  - Tranylcypromine plus risperidone for treatment-refractory major depression.

PMID- 10917418
TI  - Detection techniques in ion analysis: what are our choices?
AB  - Trends in detection techniques for ion analysis by ion-exchange chromatography
      and capillary zone electrophoresis are reviewed. Special attention is paid to
      conductivity, UV-Vis absorbance, amperometric and potentiometric detection, mass
      spectrometry (including inductively coupled plasma MS and atmospheric pressure
      ionization MS) and post-separation reaction detection. Applications reported
      within the last few years are summarized.

PMID- 10917419
TI  - Use of ion chromatography-electrospray mass spectrometry for the determination of
      ionic compounds in agricultural chemicals.
AB  - This paper reports the use of ion chromatography-electrospray mass spectrometry
      for the separation and structure elucidation of anionic compounds in a complex
      organophosphate matrix. Conventional HPLC with ion pairing reagents, pH
      adjustments or use of buffer solutions have limited compatibility with mass
      spectrometry, as the ion pairing reagents or buffers have to be volatile to be
      introduced into the mass spectrometer. The choice of volatile additives is
      limited, resulting in poor chromatography. This paper demonstrates the use of ion
      exchange chromatography (IC) for the separation of ionic compounds, followed by
      mass spectrometry (MS) for the structure elucidation of unknowns. The anionic
      impurities are separated using an anion-exchange column with aqueous sodium
      hydroxide as the eluent. Electrospray in the negative ion mode is used to obtain
      the mass spectra. The elemental composition of an unknown component in the sample
      is determined by high-resolution mass spectrometry. The coupling of IC to MS
      provides a new analytical tool to chemists faced with the challenge of separating
      and analyzing ionic compounds in complex matrices.

PMID- 10917420
TI  - Ion-chromatographic selectivity of polyelectrolyte sorbents based on some
      aliphatic and aromatic ionenes.
AB  - An aliphatic ionene with hydroxyl group (2HP-8 ionene), mixed aliphatic-aromatic
      ionenes (3-X and 6-X ionenes), aromatic ionene (Ph-X ionene), and viologen (Dp-X
      ionene) - polymers with quaternary nitrogen atoms in the main chain served as
      modifiers in synthesising polyelectrolyte sorbents for ion chromatography. The
      selectivity of produced and several previously prepared anion exchangers was
      compared with those of aliphatic ionenes. It was found that aromatic ionenes
      having a rigid structure of polymer chains are similar to their aliphatic
      analogues with shorter chains with a high charge density. Polyelectrolyte
      sorbents based on aromatic ionenes show higher selectivity to aromatic acids
      (e.g., 1-naphthalenesulfonic acid) as compared with aliphatic ionenes due to
      specific pi-pi interactions.

PMID- 10917421
TI  - Application of neutral hydrophobic hypercrosslinked polystyrene to the separation
      of inorganic anions by ion chromatography.
AB  - Neutral hydrophobic hypercrosslinked polystyrene was shown to exhibit anion
      exchange properties in the pH range 2.6-4.3 that can be attributed to the
      presence of protonated carbonyls in the framework of the polymer. This resin does
      not contain any other heteroatoms, except oxygen, responsible for the occurrence
      of positive charge at the surface. The anion-exchange selectivity of MN-200 and
      monosized spherical hypercrosslinked polystyrene to inorganic anions with diluted
      perchloric, nitric and sulfuric acid solutions as eluent was studied and the
      selectivity was found to be different from that observed for the common anion
      exchangers. The main features of hypercrosslinked polystyrene are weak retention
      of sulphate and comparatively strong retention of nitrite that can be useful in
      practical ion chromatography. The influence of column temperature on the
      retention was investigated. Calculated adsorption heats are in the range from -2
      to 19 kJ/mol. The retention mechanism of inorganic anions on neutral
      hypercrosslinked polystyrene includes both ion-exchange and hydrophobic
      interactions.

PMID- 10917422
TI  - Simplified column-switching technology for the determination of traces of anions
      in the presence of high concentrations of other anions.
AB  - A binary eluent model was proposed to study the retention behavior of trace
      anions in the presence of high concentrations of co-eluent anions. According to
      this model, the effect of the matrix on the retention of trace anions can be
      suppressed by using a high-concentration eluent. Based on the model, a simplified
      'heart-cut' column-switching technology was proposed, in which the column
      switching time window can be determined directly by standard solution of the
      analyte. By using this technology, a detection limit of 50 microg/l was obtained
      for nitrate in the presence of 5,000 mg/l chloride and 250 mg/l sulfate. The
      effect of the matrix on the concentration efficiency of weak acid anions was
      studied according to the result of phosphate. The possibility of the
      determination of weak acid anion by the 'heart-cut' technology was also
      discussed. The technology has been applied for the determination of nitrate in
      high salinity sea water, the spike recovery is in the range of 89.2-101.3%.

PMID- 10917423
TI  - Retention behaviour of strong acid anions in ion-exclusion chromatography on
      sulfonate and carboxylate stationary phases.
AB  - Some factors influencing the retention of strong-acid anions on ion-exclusion
      columns were investigated using columns with sulfonate and carboxylate functional
      groups. The nature of the functional group on the resin, the eluent pH and the
      eluent ionic strength all significantly affected the retention and separation of
      these analytes. Retention was observed for all strong-acid anions over the eluent
      pH range 2.2-5.7 and increased with both decreasing eluent pH and increasing
      eluent ionic strength. Some separation of strong-acid anions was possible when
      using a resin with carboxylate functional groups. It has also been demonstrated
      that strong-acid anions are poor markers of column void volume for ion-exclusion
      chromatography. A more accurate value was obtained using the neutral polymeric
      material dextran blue. When using eluents of low ionic strength, poor or fronted
      peak shapes were observed. A mechanism for these observations is proposed that
      relates the shape to ionic strength changes across the peak. A system peak was
      encountered under most experimental conditions. The properties of this peak are
      discussed and a cause for the system peak postulated.

PMID- 10917424
TI  - Enhanced conductometric detection of cyanide in suppressed ion chromatography.
AB  - Weak-acid anions such as borate and cyanide, present problems in chemically
      suppressed ion chromatography, since the acids are weakly ionised, giving low
      conductivity and therefore decreased sensitivity. For borate this problem was
      overcome by converting the weak acid to its sodium salt, by the use of a second
      anion micromembrane suppressor (AMMS) as an ion exchange reactor (IER), flushed
      by EDTA reagent, to supply sodium ions for the conversion. This paper will
      discuss the use of this IER system to determine cyanide, which is also a very
      weak acid, with a similar pKa to borate. The detection limit for cyanide of 50
      microM compare favourably with indirect conductivity detection.

PMID- 10917426
TI  - Determination of tripolyphosphate in frozen cod and scallop adductor by ion
      chromatography.
AB  - We introduce a method for the determination of tripolyphosphate in frozen cod and
      scallop adductor by using ion chromatography. The tripolyphosphate was extracted
      from minced cod and scallop adductor with deionized water by ultrasonic leaching,
      and then the proteins soluble in water were precipitated with trichloroacetic
      acid and removed by filtering. An ion chromatograph with an ionpac AS11-HC anion
      exchange column, an ASRS (Anion Self Regenerating Suppression), a conductivity
      detector and a gradient pump (sodium hydroxide gradient) was used. The detection
      limit was below 5 mg tripolyphosphate/kg cod or scallop adductor. This method is
      applicable to the determination of polyphosphates in aquatic products and the
      procedures are easy to implement.

PMID- 10917425
TI  - Determination of thiosulfate, thiocyanate and polythionates in a mixture by ion
      pair chromatography with ultraviolet absorbance detection.
AB  - A sensitive ion chromatographic method has been developed for the determination
      of mixtures of thiosulfate, thiocyanate and polythionates (tri-, tetra-, penta-
      and hexathionate). The proposed method is based on the separation of the sulfur
      anions on an octadecylsilica (ODS) column with an acetonitrile-water mobile phase
      containing tetrapropylammonium salt (TPA) as an ion-pairing reagent and the
      ultraviolet absorption detection of the sulfur anions. When an acetonitrile-water
      (20:80, v/v) solution (pH 5.0) containing 6 mM TPA was used as a mobile phase at
      flow-rate of 0.6 ml min(-1), the sulfur anions were resolved within 22 min. The
      detection limits defined at S/N=3 and 230 nm were very low for all anions, except
      trithionate: 30 nM for thiosulfate, 60 nM for thiocyanate, 20 nM for
      tetrathionate, 15 nM for pentathionate and 18 nM for hexathionate. The proposed
      method gave recoveries ranging from 95.0 to 105.0% when applied to the
      determination of polythionates added to hot spring waters.

PMID- 10917427
TI  - Novel way of separating polyfluorocarboxylic acids by ion-exclusion
      chromatography.
AB  - Ion-exclusion chromatography has been successfully applied to the separation of a
      number of polyfluorocarboxylic acids. The separation of various mono- and dibasic
      polyfluorocarboxylic acids having a different alkyl group was investigated using
      a polymethacrylate-based weakly acidic cation-exchange resin (TSK gel OApak-A) in
      the H -form and conductimetric detection. When water was used as the eluent,
      polyfluorocarboxylic acids could not be resolved. When an aqueous solution of
      sulfuric acid, benzoic acid, o-phthalic acid, 1,3,5-benzenetricarboxylic acid,
      1,2,4,5-benzenetetracarboxylic acid, and tartaric acid was used, the separation
      of polyfluorocarboxylic acids occurred for monobasic ones. While, for fluorine
      containing dibasic acids, imperfect separation of peaks occurred. In order to
      improve their separation, the effect of an addition of organic modifiers such as
      methanol, 2,2,2-trifluoroethanol and 2H-hexafluoro-2-propanol in the eluent was
      also investigated.

PMID- 10917429
TI  - Indirect ultraviolet spectrophotometric detection in the ion chromatography of
      common mono- and divalent cations on an aluminium adsorbing silica gel column
      with tyramine-containing crown ethers as eluent.
AB  - The application of laboratory-made aluminium-adsorbing silica gel (Al-Silica) as
      a cation-exchange stationary phase to ion chromatography-indirect photometric
      detection (IC-IPD) for common mono- and divalent cations (Li+, Na+, NH+, K+, Mg2+
      and Ca2+) was carried out by using protonated tyramine (4-aminoethylphenol) as
      eluent ion. When using 1.2 mM tyramine-0.2 mM oxalic acid at pH 4.5 as eluent,
      incomplete separation of the monovalent cations and complete separation of the
      divalent cations were achieved in 17 min. Then, the addition of crown ethers in
      the eluent was carried out for the complete separation of the mono- and divalent
      cations. As a result, when using 1.2 mM tyramine--0.2 mM oxalic acid at pH 4.5
      containing either 5 mM 15-crown-5 (1,4,7,10,13-pentaoxacyclopentadecane) or 0.5
      mM and 18-crown-6 (1,4,7,10,13,16-hexaoxacyclooctadecane) as eluent, excellently
      simultaneous separation of these cations was achieved in 21 min. The proposed IC
      IPD was successfully applied to the determination of major cations in natural
      water samples.

PMID- 10917428
TI  - Analysis of oligomannuronic acids and oligoguluronic acids by high-performance
      anion-exchange chromatography and electrospray ionization mass spectrometry.
AB  - Oligomannuronic acids and oligoguluronic acids were prepared by enzymatic
      hydrolysis of alginate with alginate lyases. The oligosaccharides generated up to
      degree of polymerization 16 were characterized by high-performance anion-exchange
      chromatography (HPAEC) with pulsed amperometric detection (PAD) and electrospray
      ionization mass spectrometry (ESI-MS). Acetate buffer linear gradients were used
      as mobile phases for separations of oligosaccharides. ESI-MS and HPAEC-PAD are
      very effective for the analysis and characterization of anionic oligosaccharides.

PMID- 10917430
TI  - Ion-chromatographic behavior of alkali metal cations and ammonium ion on
      zirconium-adsorbing silica gel.
AB  - The preparation and evaluation of zirconium-adsorbing silica gel (Zr-Silica) as
      an ion-exchange stationary phase in ion chromatography for inorganic anions and
      cations was carried out. The Zr-Silica was prepared by the reaction of silanol
      groups on the surface of the silica gel with zirconium butoxide
      (Zr(OCH2CH2CH2CH3)4) in ethanol. The ion-exchange characteristics of the Zr
      Silica were evaluated using 10 mM tartaric acid at pH 2.5 as eluent. The Zr
      Silica was found to act as a cation-exchanger under the eluent conditions. The
      retention behavior of alkali and alkaline earth metal cations was then
      investigated. The Zr-Silica column was proved to be suitable for the simultaneous
      separation of alkali metal cations and ammonium ion. Excellent separation of the
      cations on a 15 cm Zr-Silica column was achieved in 25 min using 10 mM tartaric
      acid as eluent.

PMID- 10917431
TI  - Determination of U(IV) and U(VI) by ion chromatography-inductively coupled plasma
      mass spectrometry and its application to kinetic studies.
AB  - The ions normally formed by actinides in aqueous solutions by the oxidation
      states III-VI are M3-, M4+, MO2+ and MO2(+2), respectively. Oxidation state
      representatives such as Am3+, Th4+, NpO+ and UO+, which resist oxidation state
      changes, were used to investigate a method to separate the oxidised species (MO2
      and MO2(2+)) from the reduced species (M3+ and M4+). With this method the
      hexavalent state of uranium could be separated from the tetravalent state of
      uranium in aqueous media in less than 8 min. Uranium concentrations down to 10(
      9) M could be analysed without changing the redox composition during the
      separation. The oxidation kinetics of the tetravalent uranium for different
      hydrochloric acid concentrations was investigated. The measurements showed good
      agreement with values found in the literature, although the uranium
      concentrations were one million times lower.

PMID- 10917432
TI  - Ion-chromatographic study of the possible absorption of copper and zinc by the
      skin of Rana pipiens.
AB  - Frogs are known to obtain some of their nutrients (e.g., glucose and sodium)
      through their skin. However, no studies have been made of the possible absorption
      of transition metals, which exist in most river water at low-ppb (w/w) levels.
      Therefore, this research was undertaken to evaluate the use of ion chromatography
      for such an investigation. Solutions of copper and zinc (20 ppb in each) were
      chosen for use in a small-scale screening study. Ten live frogs were each placed
      in individual baths for approximately 50 h. Of interest were the net changes in
      the concentrations of the metals. These differences were the result of any
      absorption and/or excretion processes that took place. A Dionex IonPac CS5 column
      was used to analyze this simulated river water, both before and after frogs had
      been placed in the solution. Included in this paper are: (1) methodology and
      calculation formulas; (2) precautions needed to ensure sample integrity; (3)
      statistical analyses, which indicated that ion chromatography is an accurate,
      precise technique for quantifying Cu and Zn in these samples; and (4) screening
      study results, which were used to test the null hypothesis that frogs do not
      absorb copper and zinc either onto or through their skin.

PMID- 10917433
TI  - Ion-chromatographic assay of chromium(VI)-containing semiconductor etchants
      statistical comparison of two columns.
AB  - Semiconductor etchants are concentrated-acid mixtures that are prepared under
      tight specifications. Assay procedures are needed to ensure that the proportion
      of each component is within a small percentage (usually 10 relative percent or
      less) of the target concentration. One such etchant class contains chromium
      trioxide, usually in combination with HF and HNO3, While several ion
      chromatographic columns can be used to analyze most mineral acids, chromium(VI)
      presents a problem. This latter species is highly retained by many separators and
      may also degrade the resins. This paper compares two columns that showed
      potential for success with these assays: the AS 11 and the AS16 separators (both
      from Dionex). These columns permit elution of chromium(VI) as chromate in 25 min
      or less. A representative mixture of HF, HNO3 and CrO3 was used in the research.
      Simultaneous calibration studies were conducted and the data sets analyzed
      statistically. Also investigated was the effect on the columns of repeated
      exposure to chromate.

PMID- 10917434
TI  - Suppressed electrostatic ion chromatography with tetraborate as eluent and its
      application to the determination of inorganic anions in snow and rainwater.
AB  - Tetraborate is investigated as the eluent ion for suppressed electrostatic ion
      chromatography (EIC) using a zwitterionic stationary phase. Good separation of a
      range of inorganic anions (SO4(2-), Cl-, NO3-, Br-, NO3-, ClO3-, and I-) was
      obtained, with detection limits for highly conducting ions (SO4(2-), Cl-, NO2-,
      Br- , and NO3-) being less than 8 x 10(-8) M, and for weakly conducting anions
      (ClO3- and I-) being 2.7 x 10(-7) and 5.8 x 10(-7) M, respectively. Calibration
      curves were linear up to 1.8 mM of each analyte. Retention times were found to
      increase with increasing eluent concentration and a linear relationship was
      observed between log k' and log[Na2B4O7] for all analytes. This behaviour is
      attributed to the progressive formation of a binary electrical double layer at
      the surface of the zwitterionic stationary phase. Retention times of analytes
      could be manipulated by varying the concentration of the eluent. This new
      suppressed-EIC system was applied to the determination of inorganic anions (SO4(
      2) , CI-, NO3-, NO2-, and Br-) in snow and rainwater samples.

PMID- 10917435
TI  - Simultaneous ion-exclusion/cation-exchange chromatography of anions and cations
      in acid rain waters on a weakly acidic cation-exchange resin by elution with
      sulfosalicylic acid.
AB  - A simple, selective, and sensitive method for the simultaneous determination of
      anions (sulfate, nitrate, and chloride) and cations (sodium, ammonium, potassium,
      magnesium, and calcium) in acid rain waters was developed using ion-exclusion/
      cation-exchange chromatography with conductimetric detection. A weakly acidic
      cation-exchange resin column (Tosho TSKgel OA-PAK-A) and a sulfosalicylic acid
      methanol-water eluent was used. With a mobile phase comprising 1.25 mM
      sulfosalicylic acid in methanol-water (7.5:92.5) at 1.2 ml/min, simultaneous
      separation and detection of the above anions and cations was achieved in about 30
      min. Linear calibration plots of peak area versus concentration were obtained
      over the concentration ranges 0-1.0 mM for anions (R=0.9991) and 0-0.5 mM for
      cations (R=0.9994). Detection limits calculated at S/N=3 ranged from 4.2 to 14.8
      ppb for the anions and from 2.4 to 12.1 ppb for the cations. The reproducibility
      of retention times was 0.14-0.15% relative standard deviation (RSD) for anions
      and 0.18-0.31% for cations, and reproducibility of chromatographic peak areas was
      1.22-1.75% RSD for anions and 1.81-2.10% for cations. The method was applied
      successfully to the simultaneous determination of anions and cations in aerosols
      transported from mainland China to central Japan, as determined by a
      meteorological satellite data analyzer.

PMID- 10917436
TI  - Determination of inorganic anions in environmental waters with a hydroxide
      selective column.
AB  - US Environmental Protection Agency Method 300.0 specifies the use of an IonPac
      AS4A anion-exchange column with a carbonate-hydrogencarbonate eluent and
      suppressed conductivity detection for the determination of inorganic anions in
      environmental waters by ion chromatography. Hydroxide eluents have not typically
      been used for the routine analysis of common inorganic anions due to the lack of
      an appropriate hydroxide selective column and the difficulty in preparing
      contaminant free hydroxide eluents. The use of ion chromatography with a
      hydroxide-selective IonPac AS17 column, automated eluent generation and potassium
      hydroxide gradient represents a new approach to the routine determination of
      inorganic anions in environmental waters. This new approach, which is a
      modification of Method 300.0, allows equivalent method performance with improved
      linearity, precision, and method detection limits. The AS17 column provides
      superior retention of fluoride from the column void volume and improved
      resolution from small organic acids, such as formate and acetate, compared to the
      AS4A column. Quantitative recoveries were obtained for all the common inorganic
      anions spiked into typical environmental waters using this new approach, and the
      Performance Based Measurement System Tier 1 method validation quality control
      acceptance criteria are well within the acceptable ranges defined by Method
      300.0. In addition, the EG40 eluent generator eliminates the need to manually
      prepare eluents, increasing the level of automation and ease-of-use of the ion
      chromatography system.

PMID- 10917437
TI  - Determination of chloride, sulfate and nitrate in groundwater samples by ion
      chromatography.
AB  - Groundwater is a significant source of water for both domestic and agricultural
      use in some regions of the Maracaibo lake basin in Venezuela. Chemically
      suppressed ion chromatography with a Dionex Model 2000i/sp, lonpac AS11, ASRS-I
      system was used for the analysis of major inorganic anions in groundwater
      samples. About 50 samples of groundwater, taken over several months in three
      different locations, were analyzed after filtration and sometimes dilution. In
      all the samples, the separation between the peaks of chloride, nitrate and
      sulfate showed good resolution (symmetrical peaks, not broadened), even when the
      chloride concentration was as high as 850 mg l(-1) and reproducibility (RSD) was 
      2%. No other peaks (i.e. fluoride, nitrite and phosphate) were observed at
      selected experimental conditions. With the chosen parameters, the method is well
      suited for the routine determination of these anions in groundwater samples,
      giving results in less than 10 min (including column clean-up). With an
      appropriate combination of detector output ranges (300 and 1,000 microS), only
      one set of calibration solutions was needed for all samples. In the Sierra
      Maestra location, the groundwater samples, were significantly different in total
      anion levels. Mean total chloride plus sulfate concentrations (approximately 525
      mg l(-1)) were about 100 times higher than in the other sites. Some water quality
      implications of these groundwater samples are also discussed.

PMID- 10917438
TI  - Comparison of on-line coupling of ion-chromatography with atmospheric pressure
      ionization mass spectrometry and with inductively coupled plasma mass
      spectrometry as tools for the ultra-trace analysis of bromate in surface water
      samples.
AB  - Ion chromatography in combination with atmospheric pressure ionization mass
      spectrometry (API-MS) as well as with inductively coupled plasma mass
      spectrometry (ICP-MS) had been compared for trace analysis of bromate. The
      results indicate that both techniques yield comparable results, which are in
      excellent agreement with standard methods for bromate determination. Furthermore,
      both techniques showed almost equal absolute detection limits (approximately 50
      pg bromate injected). Contrary to IC-API-MS, IC-ICP-MS can tolerate a higher salt
      concentration in the mobile phase. This allows the use of high-capacity columns
      combined with large sample volumes. This lowered the concentration based
      detection limits by one order of magnitude for IC-ICP-MS compared to IC-API-MS
      (0.06 microg/l vs. 0.5 microg/l). On the other hand, IC-API-MS is able to allow a
      positive identification of bromate even in cases when IC does not fully separate
      bromate from other bromine-containing species. The performance data of both IC-MS
      techniques have been established by participation in an international round robin
      test.

PMID- 10917439
TI  - Performance evaluation of a method for the determination of bromate in drinking
      water by ion chromatography (EPA method 317.0) and validation of EPA method
      324.0.
AB  - The potential carcinogenic nature of bromate has prompted global regulatory
      agencies, and industrial and academic institutions to publish several methods for
      the analysis of bromate in both drinking and bottled waters. The United States
      Environmental Protection Agency (EPA) has reported two methods capable of
      detecting bromate at or below the promulgated maximum contaminant level of 10.0
      microg/l. These methods are EPA Method 300.1 and 317.0. Method 300.1 has been
      promulgated by EPA for compliance monitoring of bromate under Stage 1 of the
      Disinfectants/Disinfection By-Products Rule. Due to its sensitivity, selectivity
      and simplicity, Method 317.0 has been drafted and evaluated for potential use as
      a future compliance monitoring method. This manuscript describes the performance
      evaluation work with Method 317.0 and efforts completed at EPA's Technical
      Support Center that improved the sensitivity of Method 317.0, leading to the
      development of EPA Method 324.0

PMID- 10917440
TI  - Determination of inorganic and organic anionic arsenic species in water by ion
      chromatography coupled to hydride generation-inductively coupled plasma atomic
      emission spectrometry.
AB  - The development of an analytical methodology for the specific determination of
      arsenite, arsenate and the organic species monomethylarsonic acid (MMA) and
      dimethylarsinic acid (DMA), is described. The method is based on an ion
      chromatographic separation, coupled on-line to post-column generation of the
      gaseous hydrides by reaction with sodium tetrahydroborate in acidic medium.
      Detection and measurement were performed by inductively coupled plasma
      spectrometry operated in the atomic emission mode. Arsenic emission was monitored
      at 193.7 nm. Different types and sizes of anion-exchange columns, silica and
      polymeric, were tested using EDTA as eluent. Composition, acidity and flow-rate
      of the mobile phase were optimized in order to obtain the required resolution.
      Complete elution and resolution of the four species was achieved in about 6 min.
      Linear calibration curves were obtained in the 0.05-2 microg ml(-1) range for
      As(III), As(V) and MMA, and between 0.1 and 2.0 microg ml(-1) for DMA. The
      absolute limits of detection for 200-microl sample injections were in the ng
      range, with DMA the compound measured with less sensitivity. Results of the
      analyses of natural samples, such as river and ground waters spiked with the
      studied species, suggested that analyte recoveries might be dependent on the
      sample composition.

PMID- 10917441
TI  - Determination of inorganic cations in brine solutions by ion chromatography.
AB  - The method for analysis of inorganic cations in brine solutions was developed.
      Ion chromatography is a well-established and accepted technique in the
      determination of a variety of inorganic ions. However, there are significant
      complications when ion chromatography is used to determine trace concentrations
      of inorganic ions in brine matrices. The brine solution in our study was made to
      simulate the solution from the Waste Isolation Pilot Plant. Instrumental
      parameters such as eluent composition, flow-rates, and sample loop volumes were
      investigated to arrive at the optimum condition for the determination of the
      cations with minimal dilution. Separation was carried out in a Dionex CG12A/CS12A
      with 8.25 mM H2SO4 as eluent at 1.2 ml/min flow-rate. Our results indicated that
      ion chromatography is an accurate and a good alternative method for the analysis
      of cations in brine solution.

PMID- 10917442
TI  - Trace analysis of heavy metals in groundwater samples by ion chromatography with
      post-column reaction and ultraviolet-visible detection.
AB  - Groundwaters originating from local and regional aquifers surrounding ash
      deposits produced by a coal-fired power plant were collected. These water samples
      were chemically analyzed for quantifying their heavy metal composition at trace
      levels. A highly sensitive analytical technique based on ion chromatography with
      a UV-Vis detector and under isocratic eluent flow-rate conditions was used. In
      order to quantify the major heavy metals (Pb, Cu, Cd, Co, Zn and Ni), three ionic
      separation column systems were evaluated: (1) a cationic column (HPIC-CS2,
      Dionex) tested with two eluents (10 mM oxalic acid-7.5 mM citric acid; and 40 mM
      D-tartaric acid-12 mM citric acid); (2) an anionic column (HPIC-AS4, Dionex)
      evaluated with 25 mM oxalic acid as eluent: and (3) a bifunctional ion-exchange
      column (Ionpac CS5, Dionex) which was also tested with two eluents (6 mM
      pyridine, 2,6-dicarboxylic acid; and 50 mM oxalic acid/95 mM lithium hydroxide).
      The lowest detection limits achieved with the Ionpac CS5 column and the 50 mM
      oxalic acid-95 mM lithium hydroxide eluent enabled the heavy metal analysis in
      groundwater samples to be reliably performed. Details of this comparative study,
      including the ion chromatography procedure selected and its application to heavy
      metal analysis of groundwater samples, are presented in this work.

PMID- 10917443
TI  - Determination of some pesticides and intermediates by ion chromatography.
AB  - We explored the possibility of determining some pesticides and process
      intermediates by ion chromatography. Some applications of this technique,
      standardized and adopted to meet the requirements of Gharda Chemicals (which is a
      leading producer of agrochemicals in India), will be presented in this
      communication. These include analysis of the finished products [(a) dicamba
      dimethylamine (DMA)/potassium/sodium salt acid and (b) 2,4-dichlorophenoxyacetic
      acid (2,4-D)], and the process intermediates [(c) tetrachlorobutyric acid and (d)
      glyoxylic acid/glycollic acid/formic acid]. Ion chromatographic analysis of sub
      ppm levels of 2,5-dibromo- and monochlorobromo-phenols, in 2,5-dichlorophenol,
      after adequate sample preparation steps, is also being presented.

PMID- 10917444
TI  - Determination of epichlorohydrin by ion chromatography.
AB  - In this work we developed a new method for epichlorohydrin determination with
      suppressed ion chromatography. The technique is based on a reaction between the
      analyte and sulfur(IV) to form a product with a terminal sulfonate group that can
      be analyzed by anion-exchange chromatography. The reaction conditions were
      optimized as a function of temperature, type and concentrations of reagents and
      pH. Due to the characteristics of the product formed, the columns used were an
      lonPac AS 11 and AS II-HC with a NaOH eluent. The eluent concentration was
      optimized in order to achieve a complete separation of epichlorohydrin, chloride
      and nitrate ions, commonly occurring in drinking waters. In order to improve the
      detection limits, a preconcentration step, using reversed-phase materials, has
      been optimized. The method developed was suitable for epichlorohydrin
      determination in drinking water.

PMID- 10917445
TI  - Recent developments in the separation of inorganic and small organic ions by
      capillary electrophoresis.
AB  - Which method should I use for ion analysis, ion chromatography (IC) or capillary
      electrophoresis (CE)? In terms of actual theoretical plates CE has a clear-cut
      advantage. The separation ability of IC is adequate for many sample types, and
      many separation scientists feel that IC offers greater reliability and confidence
      than CE. However, IC is a more mature technique and there has been more time to
      solve problems such as peak tailing and to improve reproducibility. The two
      techniques should be viewed as complementary. A number of recent developments in
      ion analysis by CE are discussed. These include some simple ways to control
      electroosmotic flow and improve reproducibility, separation of isotopes, improved
      methods of indirect photometric detection, a new contactless conductivity
      detector, separation of ions at low pH, and in solutions of high salt content.
      Progress in a new technique called IC-CE will be described in which a soluble ion
      exchange polymer is added to the capillary electrolyte to separate anions based
      on differences in both electrophoretic mobility and ion-exchange interactions.

PMID- 10917446
TI  - Behavior of basic compounds in ion-exchange capillary electrochromatography with
      low-pH carrier electrolytes.
AB  - This work describes the separation of basic aromatic compounds by capillary
      electrochromatography employing acidic carrier electrolytes and bare silica as
      well as strong cation-exchange stationary phases. A mixed-mode separation
      mechanism was involved, comprising chromatographic interactions (adsorption, ion
      exchange) as well as electrophoretic migration. The influence of ion-exchange on
      the retention/migration of the solutes could be manipulated according to
      procedures commonly employed in ion chromatography. These include variations of
      the eluting strength and/or the concentration of the competing ion present in the
      background electrolyte. Using this approach, separation times could be shortened
      and changes in selectivity could be achieved for a number of analytes.

PMID- 10917447
TI  - Elution mechanism in electrostatic ion chromatography with histidine as an
      isoelectric ampholytic mobile phase.
AB  - Electrostatic ion chromatography (EIC) using a zwitterionic stationary phase
      (formed by coating a C18 material with a hydrophobic zwitterionic surfactant) was
      studied with a mobile phase comprising an aqueous solution of histidine at the pH
      of its isoelectric point, together with non-suppressed conductometric detection.
      Anions and cations were found to be eluted as separate peaks, unlike the elution
      behaviour observed on the same system when pure water was used as mobile phase.
      An explanation was suggested in terms of protonation equilibria of the overall
      uncharged histidine to form small amounts of histidine cations and anions in the
      mobile phase which could act as counterions for analyte anions and cations. This
      suggestion was supported by measured pH changes occurring in the bands of eluted
      analyte anions (a decreased pH compared to the mobile phase) and cations (an
      increased pH compared to the mobile phase). The analytical potential of this type
      of EIC is discussed.

PMID- 10917448
TI  - Applications of a sulfonated-polymer wall-modified open-tubular fused-silica
      capillary in capillary zone electrophoretic separations.
AB  - A fused-silica capillary that is wall-modified via chemically bonding a
      sulfonated polymer to the capillary wall has a uniform negative charge density on
      its surface and produces an electroosmotic flow (EOF) greater than 4 x 10(-4) cm2
      V(-1) s(-1) The EOF is nearly independent of buffer pH over the pH range of 2 to
      10 and is lower than the EOF obtained for the bare fused-silica capillary at the
      more basic pH but is higher at the more acidic buffer pH. Optimization of buffer
      pH can be based on analyte pKa values to improve the overall quality of the
      capillary zone electrophoresis (CZE) separation of complex mixtures of weak acid
      and base analytes. Because of the high EOF in an acidic buffer, the capillary is
      useful for the separation of weak organic bases which are in their cation forms
      in the acidic buffer. EOF for the sulfonic acid bonded phase capillary can be
      adjusted via buffer additives such as organic solvent, tetraalkylammonium salts,
      multivalent cations and alkylsulfonic acids. The advantages of utilizing buffer
      pH and the EOF buffer modifiers to enhance migration time, selectivity, and
      resolution in CZE separations with this capillary are illustrated using a series
      of test analyte mixtures of inorganic anions, carboxylic acids, alkylsulfonic
      acids, benzenesulfonic acids, sulfas, pyridines, anilines or small-chain
      peptides.

PMID- 10917449
TI  - Ultra-rapid analysis of nitrate and nitrite by capillary electrophoresis.
AB  - Rapid analysis of nitrate and nitrite by capillary electrophoresis (CE) has been
      limited by the ions' very similar electrophoretic mobilities. With a pKa of 3.15,
      the mobility of nitrite can be selectively reduced using a low pH buffer in CE. A
      much shorter capillary can be used and separation voltages can be increased. With
      this method, nitrate and nitrite are separated in just over 10 s. This is roughly
      20 times faster than current separation methods. Direct UV detection at 214 nm
      was employed and offered sub microM detection limits. Total analysis time (pre
      rinse, injection, and separation) was less than 1 min, making this method ideal
      for high-throughput analysis.

PMID- 10917451
TI  - Peptide science--whither thou goest?

PMID- 10917450
TI  - Improved capillary electrophoresis method for measuring rare-earth elements in
      synthetic geochemical standards.
AB  - An improved capillary electrophoresis (CE) method for quantifying rare-earth
      elements (REEs) in synthetic geochemical standards was developed. Synthetic
      standard solutions were obtained from high purity metal oxides. The separation of
      REE total group (lanthanum to lutetium) was defined as a primary objective.
      Special attention was also focused on the optimized separation of europium (Eu)
      and gadolinium (Gd) because in earlier applications they presented overlapping
      problems. Their separation and quantitative determinations are essential for
      geological applications. For the rapid separation of REEs in synthetic
      geochemical standards, the temperature of the separation device was optimized. An
      analysis temperature of 15 degrees C enabled both the rapid separation of REEs
      within 2 min and the overlapping problem of Eu-Gd to be resolved. The detection
      limits (<0.1 ng) and precision estimates (generally better than 5%) were found to
      be satisfactory for most geological applications.

PMID- 10917452
TI  - Carbopeptides: carbohydrates as potential templates for de novo design of protein
      models.
AB  - De novo design of proteins has evolved into a powerful approach for studying the
      factors governing protein folding and stability. Among the families of structures
      frequently studied is the 'four-helix bundle' in which four alpha-helical peptide
      strands, linked by loops, form a hydrophobic core. Assembly of protein models on
      a template has been suggested as a way to reduce the entropy of folding. Here we
      describe the potential use of a carbohydrate as such a template. The
      monosaccharide D-galactose was per-O-acylated with (Nbeta-Fmoc-betaAla)2O to give
      a penta-substituted derivative, which was converted to the corresponding glycosyl
      bromide and used for the glycosylation of 4-hydroxymethylbenzoic acid
      pentafluorophenyl ester (HMBA-OPfp). The beta-glycosidic carbohydrate template
      (Nbeta-Fmoc-3Ala)4-beta-D-Galp-(1-O)-MBA-OPfp thus obtained was coupled to a PAL
      PEG-PS resin and simultaneously extended at the four arms to yield, after
      cleavage from the solid support, a carbopeptide with four identical peptide
      strands. Extension of this concept to, for example, synthesis of novel multiple
      antigenic peptides (MAPs) and synthesis of carbohydrate clusters can be easily
      envisioned. The ability to efficiently synthesize such structures sets the stage
      for further studies to test whether the carbohydrate templates do indeed nucleate
      folding.

PMID- 10917453
TI  - Sequencing and model structure of a Naja naja atra protein fragment.
AB  - We report the amino acid sequence of a basic protein isolated from the snake
      venom of Naja naja atra. An automated Edman sequencer was used to determine the
      65-residue sequence, aided by electrospray ionization/mass spectrometry. Online
      reduction and pyridylethylation of the peptide was performed to identify the
      cysteine residues. Trypsin, chymotrypsin and aspartic digestions were carried out
      to derive peptide fragments for further sequencing. Fragmented peptides were
      overlapped to obtain the complete sequence. Molecular mass measurements of the
      whole protein and its fragments were used as a countercheck for sequence
      assignment. Further confirmation of the sequence was indicated by sequence
      homology to other snake venom neurotoxins. A molecular model of the tertiary
      structure was constructed based on sequence homology, and was refined by global
      minimization and extensive quality control algorithms. Electrostatic and
      hydrophobic surface calculations and molecular dynamics simulations were carried
      out to determine the functional properties of the molecule.

PMID- 10917454
TI  - Position 13 analogs of the tridecapeptide mating pheromone from Saccharomyces
      cerevisiae: design of an iodinatable ligand for receptor binding.
AB  - Analogs of the alpha-factor tridecapeptide mating pheromone (WHWLQLKPGQPMY) from
      Saccharomyces cerevisiae in which Tyr13 was replaced with Phe, p-F-Phe, m-F-Phe,
      p-NO2-Phe, p-NH2-Phe or Ser were synthesized and purified to >99% homogeneity.
      These analogs were bioassayed using a growth arrest assay and a gene induction
      assay and evaluated for their ability to compete with binding of tritiated alpha
      factor to its receptor Ste2p. The results showed that the phenolic OH of Tyr13 is
      not required for either biological activity or receptor recognition. Analogs
      containing fluorine, amino, nitro or a hydrogen in place of OH had 80-120% of the
      biological activity of the parent pheromone in the gene induction assay and had
      receptor affinities from nearly equal to 6-fold lower than that of alpha-factor.
      In contrast, substitution of Ser or Ala at position 13 resulted in a >100-fold
      decrease in receptor affinity suggesting that the aromatic ring is involved in
      binding to the receptor. The lack of a strict requirement for Tyr13 allowed the
      design of several multiple replacement analogs in which Phe or p-F-Phe were
      substituted at position 13 and Tyr was placed in other positions of the peptide.
      These analogs could then be iodinated and used in the development of a highly
      sensitive receptor-binding assay. One potential receptor ligand
      [Tyr(125I)1,Nle12, Phe13] alpha-factor exhibited saturable binding with a KD of
      81 nM and was competed by alpha-factor for binding in a whole-cell assay. Thus a
      new family of radioactive ligands for the alpha-factor receptor has been
      revealed. These ligands should be extremely useful in defining active site
      residues during mutagenesis and cross-linking studies.

PMID- 10917455
TI  - Role of azaamino acid residue in beta-turn formation and stability in designed
      peptide.
AB  - The structural perturbation induced by C(alpha)-->N(alpha) exchange in azaamino
      acid-containing peptides was predicted by ab initio calculation of the 6-31G* and
      3-21G* levels. The global energy-minimum conformations for model compounds, For
      azaXaa-NH2 (Xaa=Gly, Ala, Leu) appeared to be the beta-turn motif with a dihedral
      angle of phi= +/- 90 degrees, psi=0 degrees. This suggests that incorporation of
      the azaXaa residue into the i+2 position of designed peptides could stabilize the
      beta-turn structure. The model azaLeu-containing peptide, Boc-Phe-azaLeu-Ala-OMe,
      which is predicted to adopt a beta-turn conformation was designed and synthesized
      in order to experimentally elucidate the role of the azaamino acid residue. Its
      structural preference in organic solvents was investigated using 1H NMR,
      molecular modelling and IR spectroscopy. The temperature coefficients of amide
      protons, the characteristic NOE patterns, the restrained molecular dynamics
      simulation and IR spectroscopy defined the dihedral angles [ (phi i+1, psi i+1)
      (phi i+2, psi i+2)] of the Phe-azaLeu fragment in the model peptide, Boc-Phe
      azaLeu-Ala-OMe, as [(-59 degrees, 127 degrees) (107 degrees, -4 degrees)]. This
      solution conformation supports a betaII-turn structural preference in azaLeu
      containing peptides as predicted by the quantum chemical calculation. Therefore,
      intercalation of the azaamino acid residue into the i+2 position in synthetic
      peptides is expected to provide a stable beta-turn formation, and this could be
      utilized in the design of new peptidomimetics adopting a beta-turn scaffold.

PMID- 10917456
TI  - Isolation and characterization of insulin from the Brockmann body of Dissostichus
      mawsoni, an Antarctic teleost fish.
AB  - The Brockmann body of fish synthesizes and secretes insulin. The Brockmann body
      of Antarctic fish has been described anatomically and shown to contain insulin
      immunoreactive sites, however, the primary structure of an Antarctic fish insulin
      has yet to be reported. Insulin was isolated from the Brockmann bodies of the
      Antarctic perciform teleost, Dissostichus mawsoni. The peptide was purified to
      homogeneity by gel filtration and reversed-phase HPLC. Insulin-containing
      fractions were identified by radioimmunoassay using antisera raised against
      porcine insulin. Electrospray ionization-mass spectrometry determined the mass of
      the isolated product to be 5725.27 a.m.u. The amino acid composition and primary
      structure were determined for the pyridylethylated A- and B-chains. The amino
      acid sequences of the A chain and B chain were H-Gly-lle-Val-Glu-Gln-Cys-Cys-His
      Gln-Pro10-Cys-Asn-Ile-Phe- Asp-Leu-Gln-Asn-Tyr-Cys20-Asn-OH and H-Ala-Pro-Gly-Pro
      GIn-His-Leu-Cys-Gly-Ser10-His-Leu-Val-Asp-Ala-Le u-Tyr-Leu-Val-Cys20-Gly-Glu-Arg
      Gly-Phe-Phe-Tyr-Asn-Pro-Lys30++ +-OH, respectively. The primary structure of
      insulin from Antarctic fish is compared with known structures of insulin from
      other vertebrates.

PMID- 10917457
TI  - Entrapping unusual folding characteristics of the beta-Ala residues in a model
      peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3.
AB  - Crystal structure analysis of a model peptide: Boc-beta-Ala-Aib-beta-Ala-NHCH3
      (beta-Ala: 3-amino propionic acid; Aib: alpha-aminoisobutyric acid) revealed
      distinct conformational preferences for folded [phi approximately 136 degrees, mu
      approximately -62 degrees, psi approximately 100 degrees] and semifolded [phi
      approximately 83 degrees, mu approximately -177 degrees, psi approximately -117
      degrees] structures of the N-and C-terminus beta-Ala residues, respectively. The
      overall folded conformation is stabilized by unusual Ni...H-Ni+1 and
      nonconventional C-H...O intramolecular hydrogen bonding interactions.

PMID- 10917458
TI  - Effect of physiologic vs UV pathogenic stress on immunity reactions and
      tolerance, via immunocyte traffic and homing.

PMID- 10917459
TI  - Life events, coping and breast cancer: state of the art.
AB  - In this article the state of the art regarding the possible link between life
      events and the onset and/or prognosis of breast cancer is reviewed. We can
      conclude that at this moment there exists no evidence for the contribution of
      stressful life events to an increased risk of breast cancer in studies of good
      methodological quality. Only studies of weak methodological quality suggest a
      relationship between stressful life events and risk of breast cancer. There is a
      need for studies using a straightforward prospective design. The contribution of
      life events to the prognosis of breast cancer is small. However, the role of
      coping is much greater. Coping with the diagnosis of breast cancer in a passive
      way is associated with a shorter survival time. However, studies of good
      methodological quality will be needed to replicate the link between coping and
      the prognosis of breast cancer.

PMID- 10917460
TI  - Adrenocortical responses to psychological stress and risk for hypertension.
AB  - Excessive and prolonged stress-induced cortisol changes may contribute to or be a
      marker of essential hypertension. Cortisol is a central component of the stress
      response, and it interacts with sympathetic and renal mechanisms contributing to
      increased blood pressure (BP). Although research in individuals with already
      established hypertension failed to show consistent abnormalities in
      adrenocortical output, cortisol responses to psychological stress are greater and
      more persistent in persons at high risk for hypertension relative to low-risk
      normotensives. Considering the heterogeneous and multifactorial polygenic nature
      of hypertension and the fact that cortisol affects several BP related processes,
      and regulates expression of genes involved in BP, it is possible that this
      hormone is involved in at least a sub-type of hypertension. Recent studies
      evaluating cortisol tissue sensitivity, cortisol production and cortisol
      metabolic rate in hypertension-prone persons support the possibility that
      cortisol may serve as an intermediate phenotype of hypertension. In this review,
      we discuss components of the stress responses, factors influencing the
      adrenocortical response, adrenocortical activity in hypertension, and we propose
      pathways that mediate effects of stress-induced cortisol on BP.

PMID- 10917461
TI  - Stress-induced immunomodulation: impact on immune defenses against infectious
      disease.
AB  - It is now accepted that there are complex interactions among the central nervous
      system, the endocrine system, and the immune system. Although the mechanisms of
      this bi-directional communication is not yet fully understood, studies in the
      field of psychoneuroimmunology (PNI) have shown that stress, through the
      hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal medullary (SAM)
      axes, can induce modulation of the immune system. In this review, we discuss
      human studies and animal models, which focus on psychological stress and its
      effects on the immune defense against infectious agents, emphasizing the
      implications of these effects on health.

PMID- 10917462
TI  - Social support and cardiovascular reactivity.
AB  - Recent experimental work on the benefits of social support in buffering
      cardiovascular stress responses builds on prior epidemiological, psychological,
      and physiological work. Epidemiological data show that social integration is
      associated with better health, but cannot unambiguously establish causality (it
      could be that healthy people attract more friends), nor that the mechanism is
      psychological (the mechanism could be behavioral; for example, with friends
      encouraging exercise). Social psychological work suggests that people prefer to
      be with others, especially in times of stress, and that they evaluate themselves,
      and their emotional responses, by observing the people around them. This work,
      while establishing a desire for affiliation, does not show that being with others
      translates into health benefits. Physiological evidence suggests that exaggerated
      cardiovascular responses to stress are associated with the development of
      hypertension and cardiovascular disease, but does not indicate how such
      potentially damaging stress responses can be reduced. Experimental work on social
      support and cardiovascular reactivity overcomes many of these limitations. The
      presence of an ally, especially a female, markedly reduces cardiovascular
      responses compared both to the presence of an non-supportive other, and to
      experiencing the stress alone. One fruitful area for further work is the role of
      social support following stress, both in speeding the cardiovascular return to
      pre-stress levels, and in limiting rumination-induced cardiovascular responses.

PMID- 10917463
TI  - Stress and skin diseases in musicians: evaluation of the beck depression scale,
      general psychologic profile (the brief symptom inventory [BSI]), beck anxiety
      scale and stressful life events in musicians.
AB  - We had previously investigated skin problems of musicians (N = 117) working in a
      professional orchestra. The results of this survey suggest a significant
      incidence of occupational and stress-related skin problems in musicians such as
      hyperhydrosis, lichen planus, psoriasis, seborrheic dermatitis and urticaria. It
      was thought that emotional factors exacerbate their problems [6]. This article
      discusses the importance of psychiatric consultations in dermatologic problems.

PMID- 10917464
TI  - The role of brain histamine in acute and chronic stresses.
AB  - As a neurotransmitter or neuromodulator, brain histamine has a variety of
      physiological roles in brain functions. Acute stress increases the histamine
      turnovers in the diencephalon, nucleus accumbens and striatum. Histamine
      regulates anterior pituitary hormones. Anxiolytic drugs also decrease brain
      histamine turnover. Histamine H1 receptor antagonists and H3 receptor agonists
      decrease the anxiety state. These findings show that acute stresses increase
      brain histamine turnover, especially in the diencephalon, which would be partly
      related to the pathology of anxiety. Moreover, chronic restraint stress continued
      to increase the histamine turnovers in the nucleus accumbens and striatum, not in
      the diencephalon. Chronic administration of psychostimulants also increase the
      striatal histamine release. Histamine agonists prevent psychostimulant-induced
      behavior and the development of behavioral sensitization. These results indicate
      that chronic stress continues to increase the histamine turnovers in the nucleus
      accumbens and striatum, which would have a role of preventing stress
      vulnerability. Moreover, histamine H3 receptor antagonists have antidepressive
      effects. Therefore, no increase of histamine turnover in the diencephalon is
      related to the pathology of depressive state.

PMID- 10917465
TI  - Use of xenogenized (modified) tumor cells for treatment in experimental tumor and
      in human neoplasia.
AB  - The need to modify tumor cells in order to render them more "immunogenic" was
      based on the assumption that normal, nonmodified tumor cells are non- or weakly
      immunogenic and as such are unable to raise an efficient protective immune
      response. Various methods for "xenogenization" (modification of tumor cells) were
      suggested: induction of new foreign antigens, treatment with either chemicals or
      enzymes and use of mutagens. Xenogenized tumor cells by their coupling to
      proteins, and use of chemicals like DTIC (5-[3,3-dimethyl- 1-triazeno]-imidazole
      4-carboxamide), TZC (8-carbamoyl-3-methyl-imidazo[5, 1-d]- 1,2,3,5-tetrazin-4
      [3H]-one 8-carbamoyl-3-[2-chloroethyl] imidazole [5,1 -d]- 1,2,3,5-tetrazin-4[3H]
      one) and antiemetic drugs, were tested in experimental models of murine leukemia.
      Non-tumorigenic clones, xenogenization with DNA hypomethylating agents, aryl
      triazine derivatives and DTIC were evaluated for their induction of protective
      immune response in murine lymphoma. Murine plasmacytoma cells were used for
      immunization after treatment with glutaraldehyde. Viral modifications of tumor
      cells were evaluated for their ability to induce a protective tumor response in
      model systems of rat fibrosarcoma, liver metastatic rat tumor cells, lymphoid
      tumor cells and hamster tumor cells. In the case of human cancer, attempts were
      reported to use DNP-conjugated melanoma cells, mutagenic triazine compounds, an
      autologous colon tumor cell bacillus Calmette-Guerin (BCG) vaccine and
      genetically engineered vaccines for immunization. The general conclusion drawn
      from experimental tumor models and for human cancer is, that although modified
      tumor cells were found to be partially effective in experimental models, it is
      still necessary to provide more data in order to determine the effective use of
      xenogenized human tumor cells for immunotherapy.

PMID- 10917466
TI  - Serum ECP and MPO are increased during exacerbations of chronic bronchitis with
      airway obstruction.
AB  - Many studies have demonstrated that, in asthma, serum levels of eosinophil
      cationic protein (ECP) are related to the activity and severity of the disease
      and can be used to evaluate the response to steroid treatment. During
      exacerbations of chronic bronchitis, airway inflammation shows some features of
      asthmatic inflammatory processes, with recruitment of eosinophils and recovery of
      significant amounts of ECP in bronchial lavage fluid (BAL). Involvement of
      neutrophils, with high levels of myeloperoxidase (MPO), is, on the contrary,
      typical of this latter disease, and not shared with asthma. In spite of the
      information collected with BAL and bronchial biopsy studies, few data still exist
      on serum levels of these proteins in chronic bronchitis. The objective of this
      study was to assess if serum levels of ECP and MPO are specifically increased in
      exacerbations of chronic bronchitis, as compared to other non-asthmatic acute
      respiratory disturbances. Serum ECP, MPO and immunoglobulin E (IgE) levels were
      measured in 17 non-atopic patients with exacerbation of chronic bronchitis with
      airway obstruction (COPD) and in 11 control subjects seeking emergency medical
      treatment for unrelated acute respiratory problems. Spirometry was performed in
      patients able to give the necessary collaboration. All the subjects of this study
      were recruited from the emergency department. Both ECP and MPO were significantly
      increased in serum from patients with exacerbated COPD (22.2 +/- 4.1 vs 9.5 +/-
      1.4 mcg/L and 853 +/- 168 vs 375 +/- 41 mcg/L) and a strong correlation existed
      between these two variables (r = 0.782). A further control group was made of 11
      patients with stable COPD. These subjects had levels of both ECP (13.1 +/- 2.7
      mcg/L) and MPO (469 +/- 71) significantly lower than patients with exacerbated
      disease and higher than those without COPD. We conclude that serum ECP and MPO
      are increased during the exacerbations of COPD. These observations can give a
      basis for further studies aimed to evaluate the utility of these two proteins as
      markers of activity and severity of COPD.

PMID- 10917467
TI  - Intraoperative ultrasound (IOUS) is essential in the management of metastatic
      colorectal liver lesions.
AB  - Metastatic tumors to the liver account for the majority of hepatic neoplasms.
      Improvement in resection has been shown to be beneficial and has remained the
      treatment of choice, carrying a 5-year survival rate of approximately 20 to 30
      per cent. In evaluating candidates for surgery, intraoperative assessment for
      resectability is a key factor and dictates surgical approach, as well as patient
      prognosis. Historically, imaging techniques such as CT scan, magnetic resonance
      imaging, and CT arterial portography (CTAP) have been used in preoperative
      evaluation. However, the sensitivities of these diagnostic tools have been found
      to be less than optimal. Intraoperative ultrasound (IOUS) has emerged as an
      important tool in accurately staging metastatic liver disease with a sensitivity
      of 98 per cent. From 1994 to 1996, 23 patients have undergone IOUS for evaluation
      of suspected liver neoplasms in an ongoing prospective study. All patients had
      colorectal carcinoma. All patients received preoperative CT scan, and 11 patients
      with positive CT scans had CTAP. Fifteen patients were found to have colorectal
      metastasis to the liver. Surgical management in 7 of the 15 patients was modified
      because of the use of IOUS. Two patients were found to have unresectable disease
      thus abandoning hepatic resection, two were found to have additional lesions
      undetected by preoperative evaluation and were resected, and in two patients
      margins of resection were changed. One patient was found to have benign hepatic
      cysts, and no resection was performed. The use of IOUS modified the management of
      44 per cent of our patients with liver metastases. IOUS should be routinely used
      in patients undergoing liver resection for metastatic liver disease.

PMID- 10917468
TI  - Selective intraoperative cholangiography during laparoscopic cholecystectomy: how
      selective?
AB  - The necessity for intraoperative cholangiography during laparoscopic
      cholecystectomy has been debated for some time. Numerous retrospective studies
      favor selective intraoperative cholangiography. Surgeons in favor of the
      selective policy differ in their personal selective criteria. The aim of this
      prospective study was to evaluate whether intraoperative cholangiography can be
      safely omitted during laparoscopic cholecystectomy on all patients who fit a
      standard set of criteria: normal liver function tests, common bile duct diameter
      less than 10 mm, and no history of gallstone pancreatitis or jaundice. We
      undertook a prospective study on 155 consecutive patients treated in a county
      teaching hospital with symptomatic gallbladder disease who met the above standard
      set of criteria. One hundred and fifty-five patients meeting these criteria
      underwent laparoscopic cholecystectomy during a 2-year period from February 1996
      through February 1998. Data analyzed included patient history, laboratory and
      ultrasound findings, operative results, postoperative stay, and intraoperative
      and postoperative complications. The patients were followed by periodic
      interviews, physical examination, liver function tests, and/or biliary ultrasound
      for up to 3 1/2 years with a mean follow-up of 26 months for retained common bile
      duct stones. Intraoperative cholangiography was performed in only one of the 155
      patients studied to confirm common bile duct injury. There were four
      postoperative complications (2.6%) and one common bile injury (0.6%).
      Postoperative stay averaged one day. No patients, by history, biliary ultrasound,
      liver function tests or endoscopy, were found to have retained common bile duct
      stones during the follow-up period. Our study shows that intraoperative
      cholangiography is not necessary for patients undergoing laparoscopic
      cholecystectomy who have normal liver functions tests, common bile duct diameter
      less than 10 mm, and no history of gallstone pancreatitis or jaundice.

PMID- 10917469
TI  - One-stage resection and primary anastomosis following acute obstruction of the
      left colon for cancer.
AB  - The purpose of this study was to analyze the outcome in patients with acute
      obstruction of the left colon for cancer and treated by intraoperative
      decompression, on-table lavage, resection, and primary anastomosis. Between March
      1992 and May 1998, 50 patients with acute obstruction of the left colon for
      cancer underwent surgery. Of these, 39 patients (25 men and 14 women; mean age,
      65 years; range, 23-89) were treated with intraoperative decompression, on-table
      lavage, resection, and primary anastomosis. Six patients (15%) had fecal
      localized peritonitis. Left colectomies were performed in 16 patients (32%),
      partial colectomies in 19 patients (38%), and anterior resections in 4 patients
      (8%). The primary anastomosis was intraperitoneal in 29 patients (74%) and below
      the peritoneal reflection of the rectum in 10 (26%). The postoperative course was
      uneventful in 30 of the 39 cases. One patient (3%) died (within 30 days from
      surgery) from septic shock and multiple organ failure syndrome. Anastomotic
      leakage was observed in 2 patients (6%). An intra-abdominal abscess occurred in
      one case (3%). Other common complications included wound infections in 3 patients
      (8%). This experience suggests that intraoperative decompression, on-table
      lavage, resection, and primary anastomosis can be performed safely in selected
      patients with acute obstruction of the left colon for cancer than in those with
      an anastomosis in the nondiverted colon. Anastomosis below the peritoneal
      reflection is also not a contraindication.

PMID- 10917470
TI  - Visceral ischemia after cardiopulmonary bypass.
AB  - The diagnosis and management of gastrointestinal complications associated with
      cardiopulmonary bypass is often hindered by a complicated clinical picture and
      equivocal examination. To better define the incidence, risk factors, and
      mortality, we reviewed the records of all patients undergoing cardiopulmonary
      bypass from 1988 through 1996. The database for this study comprised 14,521
      patients who underwent cardiac surgery. The patients (543) with gastrointestinal
      complications were identified, and those with major complications (166) were
      individually reviewed. Major complications included pancreatitis, gastritis,
      laparotomy, gastric ulcer, cholecystitis, colonic perforation, gastrointestinal
      bleeding, diverticulitis, bowel obstruction, perforation, and visceral ischemia.
      Our results were the following. 1) Gastrointestinal complications were noted in
      3.7 per cent (543) of patients with major complications occurring in 1.2 per
      cent. In 166 patients, 187 major complications were noted. 2) Visceral ischemia,
      an infrequent but usually fatal (71%) complication, occurred in 24 (0.17%). 3) Of
      the ischemic events, 83 per cent (20 of 24) affected the bowel; with the colon
      involved 80 per cent of the time (16 of 20). 4) Patients with visceral ischemia
      were more likely to be female (relative risk 2.1), have longer pump times (92.2
      versus 74.2), have cardiac procedures other than coronary artery bypass graft
      (relative risk 2.6), and have end-stage renal disease (relative risk 16.7). We
      conclude that, given the incidence and mortality related to visceral ischemia,
      especially to the colon, patients with risk factors (end-stage renal disease,
      female sex, non-coronary artery bypass graft, and longer pump times) should
      undergo routine endoscopic examination of the colon early after bypass and when
      clinically indicated thereafter.

PMID- 10917471
TI  - Gastric adenocarcinoma of Meckel's diverticulum as a cause of colonic
      obstruction.
AB  - A 45-year-old-female patient with no prior surgical history presented with bowel
      obstruction. At laparotomy, a bulky tumor arising from the ileum, which
      completely obstructed the sigmoid colon, was found. A left hemicolectomy followed
      by a transverse colostomy and a Hartman's pouch were performed. Pathological
      examination of the specimen revealed gastric adenocarcinoma arising from a
      Meckel's diverticulum in the ileum. Malignant transformation from a Meckel's
      diverticulum is an uncommon occurrence. This case illustrates that successful
      management of a symptomatic Meckel's diverticulum, even with malignant
      transformation, can be achieved by surgical resection.

PMID- 10917472
TI  - Nonsurgical management of solid abdominal organ injury in patients over 55 years
      of age.
AB  - Age greater than 55 is often stated to be a contraindication to nonoperative
      management of intraperitoneal solid organ injury, based upon failures in early
      experiences of nonoperative therapy. Refinements in the criteria for nonoperative
      management of hepatic and splenic injuries have yielded improved success rates
      compared with those in initial reports, raising questions as to the validity of
      an age-related contraindication. A retrospective chart review of patients more
      than 55 years of age sustaining blunt hepatic and/or splenic injury at two urban
      Level I trauma centers was performed. Patients were stratified into three groups
      in which selection criteria could not consistently be determined: those managed
      nonoperatively, those managed operatively, and those who died within 24 hours.
      The purpose of this review is to identify whether age is a determinant for
      nonoperative management of abdominal solid organ injury. Eighty-eight patients
      were identified (mean age, 68.7 +/- 9.8), 17 of whom died in the emergency
      department or after operative intervention. Of the remaining 71 patients, 37 were
      originally managed nonoperatively (mean age 69.9 +/- 9.1, mean Injury Severity
      Score 19.9), 24 sustained hepatic injuries (grades I-IV), 12 sustained splenic
      injuries (grades I-III), and one patient sustained both organ injuries. Three
      patients with multisystem trauma died from complications unrelated to their solid
      organ injury (one brain death, one septic death, and one respiratory arrest). A
      single patient, with a grade I liver injury, required delayed exploration (for a
      persistent, unexplained metabolic acidosis) and underwent a nontherapeutic
      celiotomy. All but one of the 37 patients were successfully treated
      nonoperatively, for a 97 per cent success rate. We conclude that hemodynamically
      stable patients more than 55 years of age sustaining intra-abdominal injury can
      be observed safely. Age alone should no longer be considered an exclusion
      criterion for nonoperative management of intra-abdominal solid organ injury.

PMID- 10917473
TI  - Nonoperative management of blunt splenic injury in adults 55 years and older: a
      twenty-year experience.
AB  - The nonoperative management of splenic injury secondary to blunt trauma in older
      patients remains controversial. We have reviewed our experience from January 1978
      to December 1997 with selective nonoperative management of blunt splenic injury
      in adults 55 years and older. Criteria for nonoperative management included
      hemodynamic stability with any transient hypotension corrected using less than
      2,000 cm3 crystalloid infusion, a negative abdominal physical examination ruling
      out associated injuries, and a blood transfusion requirement of no more than 2
      units attributable to the splenic injury. During the study period, 18 patients
      over age 55 with radiographic confirmation of a splenic injury met the above
      criteria for nonoperative management. Their mean age was 72 years (range 56-86),
      and 13 of the 18 were female (72%). The mean Injury Severity Score was 15 (range
      4-29), with the mechanism of injury equally divided between automobile crashes
      (9) and falls (9). During a similar time period, 15 patients 55 years or older
      with splenic injury composed an operative group; these patients did not differ
      with respect to age (mean 68 years), sex (60% female), or mechanism of injury. CT
      scans of 8 patients managed nonoperatively were available and graded using the
      American Association for the Surgery of Trauma classification, with a mean score
      of 2.3 (range 2-3). Eight of the 18 nonsurgical patients received blood
      transfusions. None of the 18 patients who met the criteria for nonoperative
      management "failed" the protocol, and none were taken to the operating room for
      abdominal exploration. Two patients (11%) died of associated thoracic injuries
      after lengthy hospital stays, one at 10 days and one at 24 days. We conclude from
      our data that nonoperative management of blunt splenic injury in patients age 55
      years and older is indicated provided they are hemodynamically stable, do not
      require significant blood transfusion, and have no other associated abdominal
      injuries.

PMID- 10917475
TI  - Should needle localization breast biopsy give way to the new technology; the
      advanced breast biopsy instrumentation.
AB  - Between July 1995 and June 1997, 114 consecutive women underwent 118 breast
      biopsies for nonpalpable lesions. A limited procedure room and local anesthesia
      were used in 96.5 per cent of patients. Intravenous access was not established in
      95 per cent of patients. Oral diazepam was given to 51 per cent of patients.
      Needle localization technique was used with a success rate of 97.5 per cent and
      average operative time of 18 minutes. Breast carcinoma was found in 29 (24.6 per
      cent) biopsies. A review of 99 of the 118 mammograms showed only 45 per cent of
      the lesions being amenable to the new technology, the advanced breast biopsy
      instrumentation. Advantages of the needle localization include short operative
      time; supine position for the patient; easy access to control bleeding; ability
      to choose a cosmetic site for the skin incision; minimal tissue removal before
      reaching the lesion; ability to maintain a sterile field; and applicability to
      almost any mammographic lesion identified, whether single or multiple.
      Disadvantages include the need for a separate procedure to place the wire and
      potential of missing the lesion in 2.5 per cent, requiring additional surgery.

PMID- 10917476
TI  - Iliac vein compression syndrome: a new method of treatment.
AB  - Iliac vein compression syndrome (May-Thurner syndrome) is caused by compression
      of the left iliac vein against the pelvic rim by the right iliac artery. Serious
      vascular sequelae to the leg can result if this is not recognized and corrected
      in a timely fashion. The condition, often underdiagnosed, is thought to be
      present in approximately 20 per cent of the adult population. Previously, a major
      vascular operation with a significant hospital stay was required to correct this
      compression. As a nonsurgical option, we elected balloon dilation of the stenosed
      iliac vein, with insertion of a venous stent to maintain the restored lumen. Two
      patients who had this procedure have been followed for 12 months; venograms show
      continued patency of the iliac vein with no pressure gradient present. This
      procedure is safe and cost effective, and it requires a minimal hospital stay.

PMID- 10917474
TI  - The influence of anesthetic technique on perioperative blood pressure control
      after carotid endarterectomy.
AB  - The optimal anesthetic for use during carotid endarterectomy has been a matter of
      debate for three decades. The goal of this study is to evaluate the influence of
      anesthetic technique on perioperative hemodynamic instability after carotid
      endarterectomy. This study is a retrospective chart review and was performed in a
      community teaching hospital. All consecutive patients undergoing carotid
      endarterectomy over a 2-year period at Providence Hospital were reviewed. One
      hundred ninety-eight patients underwent 203 carotid endarterectomies. Two
      patients were excluded because of combined coronary artery bypass grafting.
      Patients underwent carotid endarterectomy and were divided into two groups on the
      basis of use of general or regional anesthesia. Blood pressure was recorded
      hourly for the subsequent 24 hours, and the doses of vasoactive medications
      received to maintain the blood pressure within 25 mm Hg of preoperative levels
      were recorded. Patients receiving general anesthesia were found to require
      significantly more sodium nitroprusside for control of hypertension compared with
      those receiving regional anesthesia (72.1 +/- 14.5 microg/kg vs 20.2 +/- 6.6
      microg/kg; P = 0.001) in the first 8 postoperative hours. No significant
      differences were noted in the doses of any other vasoactive medications used. No
      differences were found in the subsequent 16-hour period in doses of vasoactive
      medications. Patients suffering myocardial infarctions were found to receive
      higher doses of nitroglycerine, but no differences were noted in any other
      vasoactive medication used based on complications. Length of stay was longer in
      the general anesthesia group compared with the regional anesthesia group for both
      the intensive care unit (1.59 +/- 0.13 days vs 1.08 +/- 0.03 days; P = 0.001) and
      total hospital stay (5.8 +/- 0.03 days vs 4.5 +/- 0.02 days; P = 0.003). Regional
      anesthesia required lower doses of antihypertensive medication in the early
      postoperative period when compared with general anesthesia. The doses of
      vasoactive medications used had no significant impact on the complication rate.
      Regional anesthesia allowed for shorter stay in both the intensive care unit and
      total hospital stay.

PMID- 10917477
TI  - Severe carotid arterial disease: a diagnostic enigma.
AB  - The development of the duplex scanner has made the diagnosis of carotid arterial
      disease easy to those trained in its interpretation. The difficulty lies in the
      ability to define the patient population most likely to benefit from early
      diagnosis and treatment. All patients referred to the vascular laboratories at
      two major hospitals for evaluation of neurologic symptoms were entered into the
      study. The indications for the study, comorbid conditions, and medications were
      tabulated and compared with the results of the carotid duplex scan. The purpose
      was to see whether there was a relationship between the severity of carotid
      arterial disease and symptoms. A total of 5,807 carotid duplex scans were
      performed on 5,001 patients. There were 525 patients (11%) with an internal
      carotid artery stenosis of >70 per cent and 252 patients (5%) with an occlusion
      of the internal carotid artery. In addition, there were a group of 139 patients
      with severe bilateral carotid disease. Bruit and a history of known carotid
      disease were the only indications that were statistically related to severe
      carotid arterial disease. Smoking, diabetes, peripheral vascular disease, cardiac
      conditions, and hyperlipidemia were also statistically related to patients with
      significant carotid disease. This study indicates that the classic indications
      for carotid duplex scans such as transient ischemic attack, amaurosis fugax, and
      dizziness have no correlation with the severity of the disease.

PMID- 10917478
TI  - Secondary causes of intestinal obstruction: rigorous preoperative evaluation is
      required.
AB  - The clinical presentation, management and outcome of patients with small
      intestinal and large bowel obstruction unrelated to adhesive or primary colonic
      neoplastic disease is not well described. The aim of this study was to determine
      the clinical presentation, evaluation, operative management, and outcome in
      patients with secondary causes of intestinal obstruction. The medical records of
      200 patients who underwent an operation for intestinal obstruction from January
      1995 through December 1997 were reviewed. Seventy-three patients (37%) had
      secondary causes of intestinal obstruction, and these records were reviewed in
      detail. The cohort included 37 men and 36 women with a mean age of 52 +/- 2
      years. The etiology of intestinal obstruction was metastatic neoplastic
      obstruction (19%), colonic volvulus (18%), Crohn's disease (14%), herniae (11%),
      diverticular disease (7%), and miscellaneous causes (31%). Six patients (8%) had
      intestinal motor disorders and a misdiagnosis of intestinal obstruction. The
      clinical presentation of patients with secondary causes of obstruction was
      similar to typical patients with adhesive small bowel obstruction. Preoperative
      evaluation included frequent use of CT (42%), but intestinal contrast studies
      were used in 13 (18%) patients only. Two-thirds of the patients required an
      intestinal resection, and 50 per cent of the patients with a misdiagnosis had a
      nontherapeutic celiotomy. Operative mortality and morbidity were 3 per cent and
      48 per cent, respectively, and 15 per cent of patients required reoperation.
      Suspected intestinal obstruction from secondary causes requires rigorous
      preoperative evaluation with liberal use of intestinal contrast examinations to
      avoid misdiagnosis, operative complications, and reoperations.

PMID- 10917479
TI  - Sentinel lymph node biopsy in breast cancer.
AB  - One of the most important prognostic indicators in patients with breast cancer is
      axillary lymph node status. Sentinel lymph node (SLN) biopsy has emerged as a
      potential alternative to routine axillary dissection in clinically node-negative
      early breast cancer. This procedure requires a specialized but multidisciplinary
      approach utilizing the surgeon, nuclear radiologist and pathologist. SLN biopsy
      allows adequate assessment of the axillary nodal status in patients with early
      breast cancer, with minimal-if any-morbidity. Blue dye and lymphoscintigraphy are
      complementary techniques, and the success rate is maximized when the two methods
      are used together. Focused histopathologic examination on one or two lymph nodes
      most likely to contain metastases [SLN(s)], using serial sectioning and
      immunohistochemical techniques, allows an improved staging to be performed.
      Detection of metastases on SLN(s) is not only a prognostic indicator, but it also
      dictates whether the patient should receive further surgery and adjuvant
      chemotherapy. Until data regarding the long-term results of the SLN biopsy are
      available, this method should be considered investigational and be performed by
      surgeons experienced in this technique to achieve a failure rate of less than 2
      per cent.

PMID- 10917480
TI  - Sarcoidosis of the pancreas: case report and review of the literature.
AB  - Sarcoidosis involving the pancreas is rare. Patients can present with symptoms
      that mimic pancreatic cancer. We report a case of a male patient with clinical
      and radiographic findings suggestive of pancreatic cancer as the initial
      manifestation of sarcoidosis.

PMID- 10917481
TI  - Surgical repair of incisional ventral hernias: tension-free technique using
      prosthetic materials (expanded polytetrafluoroethylene Gore-Tex Dual Mesh).
AB  - Repairing an incisional ventral hernia is a major challenge for a surgeon. The
      high recurrence rates observed during hernia repair by tissue approximation led
      to development of tension-free procedures by using prosthetic materials. The
      purpose of this study is to report the results of a tension-free repair technique
      using expanded polytetrafluoroethylene Gore-Tex Dual Mesh (Gore-Tex Soft Tissue
      Patch, W.L. Gore and Associates Inc, Flagstaff, AZ) in patients with primary or
      recurrent incisional ventral hernias. Over 3 years, 52 patients with incisional
      hernias have undergone this procedure in our clinic. Fourteen of them had
      recurrent hernias which had been primarily repaired by Mayo hernioplasty. Six of
      our patients had irreducible hernias preoperatively. Twenty-five patients had
      hernias on midline incisions, and the rest of them had hernias on transverse
      abdominal incisions. The median patient age was 65 years, and all were operated
      on under general anesthesia. The majority of the patients had 4 to 6 days of
      hospitalization. A subcutaneous seroma developed in eight patients. They all were
      treated by multiple paracentesis. Four of our patients experienced wound
      infection and were treated by mesh removal. None of the patients presented with
      cardiovascular or pulmonary complications. During the follow-up period, no other
      hernia recurrence, except the cases with mesh removal, has been noticed. The
      tension-free incisional hernia repair using expanded polytetrafluoroethylene mesh
      is, to our experience, a safe and easy procedure with no major morbidity or
      recurrence.

PMID- 10917482
TI  - Tuberculous enteritis: a case report.
AB  - Tuberculous enteritis is an unusual diagnosis in the United States. Because this
      entity is rare and the symptoms are not specific, the physician must have a high
      index of suspicion. We report the case of a young man with tuberculous
      involvement of the gastrointestinal tract who required surgical intervention for
      small bowel obstruction.

PMID- 10917483
TI  - Treatment options for perianal Bowen's disease: survery of American Society of
      Colon and Rectal Surgeons Members.
AB  - The aim of this study was to determine current management practices of physicians
      caring for patients with perianal Bowen's disease. A questionnaire was sent to
      1,499 members listed in the 1997 American Society of Colon and Rectal Surgeons
      Directory asking them how many patients they have treated and which operative or
      nonoperative treatment option they choose for small (< or =3 cm), large (> 3 cm),
      and microscopic lesions. Of 1,499, 663 (44.2%) surgeons responded. Not all
      respondents answered each item. Seventy-five per cent of surgeons surveyed (n =
      653) devote greater than 75 per cent of their practice to colon and rectal
      surgery. Of 642 respondents, 552 (86%) managed a total of <10 patients, and
      90/642 (14%), > or =10 patients. Ninety-six per cent of respondents use wide
      local excision for patients with small lesions. Eighty-seven per cent of
      respondents use wide local excision for patients with large lesions. Seventy-four
      per cent treat patients with microscopic disease conservatively and without wide
      excision. The majority of surgeons caring for patients with perianal Bowen's
      disease are performing wide local excision for both small and large lesions.
      Microscopic disease was usually treated conservatively with observation alone.

PMID- 10917484
TI  - Gastric stromal tumor.
AB  - Gastric stromal tumors display a bewildering array of immunohistological and
      ultrastructural features as well as variable biological behavior. These tumors
      are rare as compared with ones that arise from the gastric epithelium. Moreover,
      they have been the subjects of controversy because of their uncertain
      histogenesis. We report the pathological features of gastric stromal tumors we
      recently encountered in three patients.

PMID- 10917485
TI  - Fatal airway compromise due to retropharyngeal hematoma after airbag deployment.
AB  - In trauma patients it is possible for a hematoma to form in the potential space
      between the pharynx and cervical spine (the retropharyngeal space). Fewer than 30
      cases of actual airway obstruction secondary to retropharyngeal hematomas have
      been reported. We present an unusual case of an elderly woman who was involved in
      a minor motor vehicle collision which deployed her airbag. She died as a result
      of anoxic injury to the brain. Autopsy results demonstrated transverse fractures
      through the bodies of C5 and C7 with associated significant retropharyngeal and
      mediastinal hematoma. Airbags have been shown to significantly decrease the
      mortality rate in frontal collisions; however, the potential for hyperextension
      injuries from airbag deployment exists, especially if the occupant is
      unrestrained, small, or sitting too close to the airbag. When this woman's airbag
      deployed, it most likely caused her vertebral fractures, hematoma, subsequent
      airway compromise, and anoxic brain injury. Whatever the mechanism of trauma, one
      must be cognizant of the potential risk for retropharyngeal hematoma and airway
      compromise when a patient presents with injury to the cervical spine.

PMID- 10917486
TI  - Aneurysm of the gastroduodenal artery: an unusual cause of obstructive jaundice.
AB  - Splanchnic artery aneurysms are among the most infrequent aneurysms that affect
      the arterial circulation. Aneurysms of the gastroduodenal artery are the rarest
      splanchnic artery aneurysms, comprising fewer than 10 per cent of all such
      lesions. The most typical presentations include abdominal pain and acute
      gastrointestinal bleeding. However, the diagnosis is often missed preoperatively.
      We report the successful surgical management of a patient with a gastroduodenal
      artery aneurysm who presented with isolated obstructive jaundice and review the
      literature on this unusual finding.

PMID- 10917487
TI  - Changes in liver function tests after laparoscopic cholecystectomy: not so rare,
      not always ominous.
AB  - The incidental findings of increased alanine aminotransferase (ALT) and aspartate
      amino transferase (AST) after uneventful laparoscopic cholecystectomy (LC)
      prompted us to investigate the incidence and the clinical significance of this
      phenomenon. Changes in liver function test after LC (n = 55) were compared with
      those after OC (n = 16). Liver function tests were obtained preoperatively and
      postoperatively on days 1, 2, and 7. All of the patients fulfilled the selection
      criteria: normal preoperative liver function test and no endoscopic retrograde
      cholangiopancreatography, common bile duct exploration, or postoperative biliary
      complications (injury, infection, or obstruction). Converted cholecystectomies
      were also excluded. During LC, the intra-abdominal pressure was maintained within
      the conventional range of 14 to 15 mm Hg. ALT had doubled in the first 48 hours
      from the preoperative mean in 58.2 per cent in LC patients versus only 6.3 per
      cent in the OC group. AST doubled from the preoperative mean value in 38.2 per
      cent in the LC group versus only 6.3 per cent in the OC group. By the 7th
      postoperative day, the enzymes returned to the preoperative values in both the LC
      and the OC group. In many instances, a significant increase in ALT and AST blood
      levels occurred after uneventful LC. The phenomenon is transient as these enzymes
      returned to normal value within 7 days. These changes are clinically silent in
      patients with a normal liver function.

PMID- 10917488
TI  - Accurate placement of microvascular guide sutures.
AB  - A simple technique to accurately place initial microvascular guide sutures is
      described. Enhanced suture placement enables anastomosis construction in
      situations in which the clamp must be placed very close to the vessel end or if
      the vessel lumen is distorted or poorly visualized. Because this technique
      eliminates the need for retraction on the guide suture tails, it is particularly
      useful for solo microvascular surgeons.

PMID- 10917489
TI  - Brigadier General Theodore C Lyster [correction of Lister], MD: father of
      American aviation medicine.
AB  - Aviation medicine came into existence as a recognized entity when certain
      standards were established during and shortly after World War I. During this
      time, accident rates were high. In fact, a larger number of pilots were dying in
      accidents than in combat. Figures from Great Britain's casualty list at the close
      of the first year of World War I indicated that for every 100 aviators killed, 60
      died as a result of some individual physical defect, 30 from some form of
      recklessness or careless behavior, 8 as a result of some mechanical defect in the
      airplane, and only 2 at the hands of the enemy. Aviators were found to be in poor
      physical condition. Because there were no established regulations with regard to
      workloads, aviators were frequently found to have been flying to a point beyond
      exhaustion. Because of workload, chronic fatigue, and emotional stress, aviators
      were constantly called upon to perform superhuman feats when not in peak physical
      condition. Errors in judgement were common. The majority of pilots lost weight as
      a somatic sign of stress. This was recognized by Theodore Lyster [corrected] who
      had recently been appointed as the Chief Surgeon, Aviation Section of the U.S.
      Army. Such problems were not diagnosed by medical officers because they were not
      trained to recognize them. Theodore Charles Lyster [corrected] was the son of
      Captain William J. and Martha Doughty Lyster [corrected]. He was an Army "brat"
      who entered the world on July 10, 1875. His childhood was spent in various posts
      around the country. At the age of 7, Lyster [corrected] contracted yellow fever
      while living in Fort Brown, TX. The boy was treated by William Gorgas, a young
      post surgeon. Gorgas was credited with the young boy's recovery. Later, Gorgas
      was to marry Lyster's [corrected] aunt making Lyster [corrected] his nephew by
      marriage. Having survived the yellow fever infection, young Lyster [corrected]
      had a lifelong immunity to the disease.

PMID- 10917491
TI  - SOS (again) at the Department of Energy.

PMID- 10917490
TI  - Grounds for hope on AIDS in Africa.

PMID- 10917494
TI  - UK space strategy slammed as lacking funds and vision

PMID- 10917493
TI  - Jordan chosen to open SESAME. Synchrotron-light for Experimental Science and
      Applications in the Middle East

PMID- 10917492
TI  - Large research facilities to lose out in science spending spree?

PMID- 10917495
TI  - Diplomatic Mandela calls for action on HIV...as South Africa considers its
      options after free drugs offer.

PMID- 10917497
TI  - Industry considers carbon catching

PMID- 10917496
TI  - Diabetes therapy boosts stem-cell campaign.

PMID- 10917498
TI  - Enhanced advisory role urged for former EU nuclear labs

PMID- 10917499
TI  - Brown boosts British science base.

PMID- 10917500
TI  - Recriminations and confusion over 'fake' coelacanth photo.

PMID- 10917501
TI  - Anti-smoking critic wins campaigning right.

PMID- 10917502
TI  - German librarians cautious of brave new digital world.

PMID- 10917503
TI  - Bones, molecules...or both?

PMID- 10917504
TI  - Caution is sensible, but give biotech a chance to show the good it can do.

PMID- 10917505
TI  - A fault in the 'weak San Andreas' theory

PMID- 10917506
TI  - That famous double helix takes a sinister turn.

PMID- 10917507
TI  - Jumbo

PMID- 10917508
TI  - All is not lost

PMID- 10917509
TI  - Faster than a speeding photon

PMID- 10917510
TI  - Biophysics. Science in motion.

PMID- 10917511
TI  - Neurobiology. Parallel sensing.

PMID- 10917512
TI  - Atmospheric physics. Enlightening water vapour

PMID- 10917513
TI  - Human behaviour. Fair game.

PMID- 10917514
TI  - Structural biology. Adding to the antifreeze agenda.

PMID- 10917515
TI  - Mathematics. Best packing in proteins and DNA.

PMID- 10917516
TI  - A protein accumulator.

PMID- 10917517
TI  - Spider manipulation by a wasp larva.

PMID- 10917518
TI  - Heat-stable antifreeze protein from grass.

PMID- 10917519
TI  - Hepatocytes from non-hepatic adult stem cells.

PMID- 10917520
TI  - Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc
      epsilonRI alpha.
AB  - The initiation of immunoglobulin-E (IgE)-mediated allergic responses requires the
      binding of IgE antibody to its high-affinity receptor, Fc epsilonRI. Crosslinking
      of Fc epsilonRI initiates an intracellular signal transduction cascade that
      triggers the release of mediators of the allergic response. The interaction of
      the crystallizable fragment (Fc) of IgE (IgE-Fc) with Fc epsilonRI is a key
      recognition event of this process and involves the extracellular domains of the
      Fc epsilonRI alpha-chain. To understand the structural basis for this
      interaction, we have solved the crystal structure of the human IgE-Fc-Fc
      epsilonRI alpha complex to 3.5-A resolution. The crystal structure reveals that
      one receptor binds one dimeric IgE-Fc molecule asymmetrically through
      interactions at two sites, each involving one C epsilon3 domain of the IgE-Fc.
      The interaction of one receptor with the IgE-Fc blocks the binding of a second
      receptor, and features of this interaction are conserved in other members of the
      Fc receptor family. The structure suggests new approaches to inhibiting the
      binding of IgE to Fc epsilonRI for the treatment of allergy and asthma.

PMID- 10917521
TI  - The 3.2-A crystal structure of the human IgG1 Fc fragment-Fc gammaRIII complex.
AB  - The immune response depends on the binding of opsonized antigens to cellular Fc
      receptors and the subsequent initiation of various cellular effector functions of
      the immune system. Here we describe the crystal structures of a soluble Fc gamma
      receptor (sFc gammaRIII, CD16), an Fc fragment from human IgG1 (hFc1) and their
      complex. In the 1:1 complex the receptor binds to the two halves of the Fc
      fragment in contact with residues of the C gamma2 domains and the hinge region.
      Upon complex formation the angle between the two sFc gammaRIII domains increases
      significantly and the Fc fragment opens asymmetrically. The high degree of amino
      acid conservation between sFc gammaRIII and other Fc receptors, and similarly
      between hFc1 and related immunoglobulins, suggest similar structures and modes of
      association. Thus the described structure is a model for immune complex
      recognition and helps to explain the vastly differing affinities of other Fc
      gammaR-IgG complexes and the Fc epsilonRI alpha-IgE complex.

PMID- 10917523
TI  - Gain-assisted superluminal light propagation
AB  - Einstein's theory of special relativity and the principle of causality imply that
      the speed of any moving object cannot exceed that of light in a vacuum (c).
      Nevertheless, there exist various proposals for observing faster-than-c
      propagation of light pulses, using anomalous dispersion near an absorption line,
      nonlinear and linear gain lines, or tunnelling barriers. However, in all previous
      experimental demonstrations, the light pulses experienced either very large
      absorption or severe reshaping, resulting in controversies over the
      interpretation. Here we use gain-assisted linear anomalous dispersion to
      demonstrate superluminal light propagation in atomic caesium gas. The group
      velocity of a laser pulse in this region exceeds c and can even become negative,
      while the shape of the pulse is preserved. We measure a group-velocity index of
      n(g) = -310(+/- 5); in practice, this means that a light pulse propagating
      through the atomic vapour cell appears at the exit side so much earlier than if
      it had propagated the same distance in a vacuum that the peak of the pulse
      appears to leave the cell before entering it. The observed superluminal light
      pulse propagation is not at odds with causality, being a direct consequence of
      classical interference between its different frequency components in an anomalous
      dispersion region.

PMID- 10917522
TI  - Determining the ages of comets from the fraction of crystalline dust.
AB  - The timescale for the accretion of bodies in the disk surrounding a young star
      depends upon a number of assumptions, but there are few observational
      constraints. In our own Solar System, measurements of meteoritic components can
      provide information about the inner regions of the nebula, but not the outer
      parts. Observations of the evolution of more massive protostellar systems (Herbig
      Ae/Be stars) imply that significant changes occur in the physical properties of
      their dust with time. The simplest explanation is that thermal annealing of the
      original, amorphous grains in the hot inner nebula slowly increases the
      fractional abundance of crystalline material over time. Crystalline dust is then
      transported outward, where it is incorporated into comets that serve as a long
      term reservoir for dust disks, such as that surrounding Beta Pictoris. Here we
      show that when applied to our own Solar System, this process can explain observed
      variations in both the volatile and dusty components of comets, while also
      providing a natural indicator of a comet's mean formation age. Studies of comets
      with different dust contents can therefore be used to investigate the timescales
      of the early Solar System.

PMID- 10917524
TI  - Non-collinear states in magnetic sensors
AB  - Certain materials have an electrical conductivity that is extremely sensitive to
      an applied magnetic field; this phenomenon, termed 'giant magnetoresistance', can
      be used in sensor applications. Typically, such a device comprises several
      ferromagnetic layers, separated by non-magnetic spacer layer(s)--a so-called
      'super-lattice' geometry. In the absence of a magnetic field, the ferromagnetic
      layers may be magnetized in opposite directions by interlayer exchange coupling,
      while an applied external magnetic field causes the magnetization directions to
      become parallel. Because the resistivity depends on the magnetization direction,
      an applied field that changes the magnetic configuration may be detected simply
      by measuring the change in resistance. In order to detect weak fields, the energy
      difference between different magnetization directions should be small; this is
      usually achieved by using many non-magnetic atomic spacer layers. Here we show,
      using first-principles theory, that materials combinations such as Fe/V/Co
      multilayers can produce a non-collinear magnetic state in which the magnetization
      direction between Fe and Co layers differs by about 90 degrees. This state is
      energetically almost degenerate with the collinear magnetic states, even though
      the number of non-magnetic vanadium spacer layers is quite small.

PMID- 10917525
TI  - Imaging the vortex-lattice melting process in the presence of disorder
AB  - General arguments suggest that first-order phase transitions become less sharp in
      the presence of weak disorder, while extensive disorder can transform them into
      second-order transitions; but the atomic level details of this process are not
      clear. The vortex lattice in superconductors provides a unique system in which to
      study the first-order transition on an inter-particle scale, as well as over a
      wide range of particle densities. Here we use a differential magneto-optical
      technique to obtain direct experimental visualization of the melting process in a
      disordered superconductor. The images reveal complex behaviour in nucleation,
      pattern formation, and solid-liquid interface coarsening and pinning. Although
      the local melting is found to be first-order, a global rounding of the transition
      is observed; this results from a disorder-induced broad distribution of local
      melting temperatures, at scales down to the mesoscopic level. We also resolve
      local hysteretic supercooling of microscopic liquid domains, a non-equilibrium
      process that occurs only at selected sites where the disorder-modified melting
      temperature has a local maximum. By revealing the nucleation process, we are able
      to experimentally evaluate the solid-liquid surface tension, which we find to be
      extremely small.

PMID- 10917526
TI  - Optimal shapes of compact strings.
AB  - Optimal geometrical arrangements, such as the stacking of atoms, are of relevance
      in diverse disciplines. A classic problem is the determination of the optimal
      arrangement of spheres in three dimensions in order to achieve the highest
      packing fraction; only recently has it been proved that the answer for infinite
      systems is a face-centred-cubic lattice. This simply stated problem has had a
      profound impact in many areas, ranging from the crystallization and melting of
      atomic systems, to optimal packing of objects and the sub-division of space. Here
      we study an analogous problem--that of determining the optimal shapes of closely
      packed compact strings. This problem is a mathematical idealization of situations
      commonly encountered in biology, chemistry and physics, involving the optimal
      structure of folded polymeric chains. We find that, in cases where boundary
      effects are not dominant, helices with a particular pitch-radius ratio are
      selected. Interestingly, the same geometry is observed in helices in naturally
      occurring proteins.

PMID- 10917527
TI  - Evidence for a link between global lightning activity and upper tropospheric
      water vapour
AB  - Tropospheric water vapour is a key element of the Earth's climate, which has
      direct effects as a greenhouse gas, as well as indirect effects through
      interaction with clouds, aerosols and tropospheric chemistry. Small changes in
      upper-tropospheric water vapour have a much larger impact on the greenhouse
      effect than small changes in water vapour in the lower atmosphere, but whether
      this impact is a positive or negative feedback remains uncertain. The main
      challenge in addressing this question is the difficulty in monitoring upper
      tropospheric water vapour globally over long timescales. Here I show that upper
      tropospheric water-vapour variability and global lightning activity are closely
      linked, suggesting that upper-tropospheric water-vapour changes can be inferred
      from records of global lightning activity, readily obtained from observations at
      a single location on the Earth's surface. This correlation reflects the fact that
      continental deep-convective thunderstorms transport large amounts of water vapour
      into the upper troposphere and thereby dominate the variations of global upper
      tropospheric water vapour while producing most of the lightning on Earth. As
      global lightning induces Schumann resonances, an electromagnetic phenomenon in
      the atmosphere that can be observed easily at low cost, monitoring of these
      resonances might provide a convenient method for tracking upper-tropospheric
      water-vapour variability and hence contribute to a better understanding of the
      processes affecting climate change.

PMID- 10917528
TI  - Melting of the Earth's lithospheric mantle inferred from protactinium-thorium
      uranium isotopic data
AB  - The processes responsible for the generation of partial melt in the Earth's
      lithospheric mantle and the movement of this melt to the Earth's surface remain
      enigmatic, owing to the perceived difficulties in generating large-degree partial
      melts at depth and in transporting small-degree melts through a static
      lithosphere. Here we present a method of placing constraints on melting in the
      lithospheric mantle using 231Pa-235U data obtained from continental basalts in
      the southwestern United States and Mexico. Combined with 230Th-238U data, the
      231Pa-235U data allow us to constrain the source mineralogy and thus the depth of
      melting of these basalts. Our analysis indicates that it is possible to transport
      small melt fractions--of the order of 0.1%--through the lithosphere, as might
      result from the coalescence of melt by compaction owing to melting-induced
      deformation. The large observed 231Pa excesses require that the timescale of melt
      generation and transport within the lithosphere is small compared to the half
      life of 231Pa (approximately 32.7 kyr). The 231Pa-230Th data also constrain the
      thorium and uranium distribution coefficients for clinopyroxene in the source
      regions of these basalts to be within 2% of one another, indicating that in this
      setting 230Th excesses are not expected during melting at depths shallower than
      85 km.

PMID- 10917529
TI  - Female bluethroats enhance offspring immunocompetence through extra-pair
      copulations.
AB  - Female birds frequently copulate with extra-pair males, but the adaptive value of
      this behaviour is poorly understood. Some studies have suggested that 'good
      genes' may be involved, where females seek to have their eggs fertilized by high
      quality males without receiving any material benefits from them. Nevertheless, it
      remains to be shown that a genetic benefit is passed on to offspring. Here we
      report that nestling bluethroats, Luscinia svecica, sired by extra-pair males had
      a higher T-cell-mediated immune response than their maternal half-siblings raised
      in the same nest. The difference could not be attributed to nestling body mass,
      sex or hatching order, but may be an effect of paternal genotype. Extra-pair
      young were also more immunocompetent than their paternal half-sibs raised in the
      genetic father's own nest, which indicates an additional effect of maternal
      genotype. Our results are consistent with the idea that females engage in extra
      pair copulations to obtain compatible viability genes, rather than 'good genes'
      per se.

PMID- 10917530
TI  - Magnetite defines a vertebrate magnetoreceptor.
AB  - The key behavioural, physiological and anatomical components of a magnetite-based
      magnetic sense have been demonstrated in rainbow trout (Oncorhynchus mykiss).
      Candidate receptor cells located within a discrete sub-layer of the olfactory
      lamellae contained iron-rich crystals that were similar in size and shape to
      magnetite crystals extracted from salmon. Here we show that these crystals, which
      mapped to individual receptors using confocal and atomic force microscopy, are
      magnetic, as they are uniquely associated with dipoles detected by magnetic force
      microscopy. Analysis of their magnetic properties identifies the crystals as
      single-domain magnetite. In addition, three-dimensional reconstruction of the
      candidate receptors using confocal and atomic force microscopy imaging confirm
      that several magnetic crystals are arranged in a chain of about 1 microm within
      the receptor, and that the receptor is a multi-lobed single cell. These results
      are consistent with a magnetite-based detection mechanism, as 1-microm chains of
      single-domain magnetite crystals are highly suitable for the behavioural and
      physiological responses to magnetic intensity previously reported in the trout.

PMID- 10917531
TI  - Transformation from temporal to rate coding in a somatosensory thalamocortical
      pathway.
AB  - The anatomical connections from the whiskers to the rodent somatosensory (barrel)
      cortex form two parallel (lemniscal and paralemniscal) pathways. It is unclear
      whether the paralemniscal pathway is directly involved in tactile processing,
      because paralemniscal neuronal responses show poor spatial resolution, labile
      latencies and strong dependence on cortical feedback. Here we show that the
      paralemniscal system can transform temporally encoded vibrissal information into
      a rate code. We recorded the representations of the frequency of whisker movement
      along the two pathways in anaesthetized rats. In response to varying stimulus
      frequencies, the lemniscal neurons exhibited amplitude modulations and constant
      latencies. In contrast, paralemniscal neurons in both thalamus and cortex coded
      the input frequency as changes in latency. Because the onset latencies increased
      and the offset latencies remained constant, the latency increments were
      translated into a rate code: increasing onset latencies led to lower spike
      counts. A thalamocortical loop that includes cortical oscillations and thalamic
      gating can account for these results. Thus, variable latencies and effective
      cortical feedback in the paralemniscal system can serve the processing of
      temporal sensory cues, such as those that encode object location during whisking.
      In contrast, fixed time locking in the lemniscal system is crucial for reliable
      spatial processing.

PMID- 10917532
TI  - Presenilin is required for proper morphology and function of neurons in C.
      elegans.
AB  - Mutations in the human presenilin genes cause the most frequent and aggressive
      forms of familial Alzheimer's disease (FAD). Here we show that in addition to its
      role in cell fate decisions in non-neuronal tissues, presenilin activity is
      required in terminally differentiated neurons in vivo. Mutations in the
      Caenorhabditis elegans presenilin genes sel-12 and hop-1 result in a defect in
      the temperature memory of the animals. This defect is caused by the loss of
      presenilin function in two cholinergic interneurons that display neurite
      morphology defects in presenilin mutants. The morphology and function of the
      affected neurons in sel-12 mutant animals can be restored by expressing sel-12
      only in these cells. The wild-type human presenilin PS1, but not the FAD mutant
      PS1 A246E, can also rescue these morphological defects. As lin-12 mutant animals
      display similar morphological and functional defects to presenilin mutants, we
      suggest that presenilins mediate their activity in postmitotic neurons by
      facilitating Notch signalling. These data indicate cell-autonomous and
      evolutionarily conserved control of neural morphology and function by
      presenilins.

PMID- 10917533
TI  - A chemokine-driven positive feedback loop organizes lymphoid follicles.
AB  - Lymphoid follicles are B-cell-rich compartments of lymphoid organs that function
      as sites of B-cell antigen encounter and differentiation. CXC chemokine receptor
      5 (CXCR5) is required for B-cell migration to splenic follicles, but the
      requirements for homing to B-cell areas in lymph nodes remain to be defined. Here
      we show that lymph nodes contain two types of B-cell-rich compartment: follicles
      containing follicular dendritic cells, and areas lacking such cells. Using gene
      targeted mice, we establish that B-lymphocyte chemoattractant (BLC/BCA1) and its
      receptor, CXCR5, are needed for B-cell homing to follicles in lymph nodes as well
      as in spleen. We also find that BLC is required for the development of most lymph
      nodes and Peyer's patches. In addition to mediating chemoattraction, BLC induces
      B cells to up-regulate membrane lymphotoxin alpha1beta2, a cytokine that promotes
      follicular dendritic cell development and BLC expression, establishing a positive
      feedback loop that is likely to be important in follicle development and
      homeostasis. In germinal centres the feedback loop is overridden, with B-cell
      lymphotoxin alpha1beta2 expression being induced by a mechanism independent of
      BLC.

PMID- 10917534
TI  - A tertiary interaction that links active-site domains to the 5' splice site of a
      group II intron.
AB  - Group II introns are self-splicing RNAs that are commonly found in the genes of
      plants, fungi, yeast and bacteria. Little is known about the tertiary structure
      of group II introns, which are among the largest natural ribozymes. The most
      conserved region of the intron is domain 5 (D5), which, together with domain 1
      (D1), is required for all reactions catalysed by the intron. Despite the
      importance of D5, its spatial relationship and tertiary contacts to other active
      site constituents have remained obscure. Furthermore, D5 has never been placed
      directly at a site of catalysis by the intron. Here we show that a set of
      tertiary interactions (lambda-lambda') links catalytically essential regions of
      D5 and D1, creating the framework for an active-site and anchoring it at the 5'
      splice site. Highly conserved elements similar to components of the lambda
      lambda' interaction are found in the eukaryotic spliceosome.

PMID- 10917535
TI  - A ratchet-like inter-subunit reorganization of the ribosome during translocation.
AB  - The ribosome is a macromolecular assembly that is responsible for protein
      biosynthesis following genetic instructions in all organisms. It is composed of
      two unequal subunits: the smaller subunit binds messenger RNA and the anticodon
      end of transfer RNAs, and helps to decode the mRNA; and the larger subunit
      interacts with the amino-acid-carrying end of tRNAs and catalyses the formation
      of the peptide bonds. After peptide-bond formation, elongation factor G (EF-G)
      binds to the ribosome, triggering the translocation of peptidyl-tRNA from its
      aminoacyl site to the peptidyl site, and movement of mRNA by one codon. Here we
      analyse three-dimensional cryo-electron microscopy maps of the Escherichia coli
      70S ribosome in various functional states, and show that both EF-G binding and
      subsequent GTP hydrolysis lead to ratchet-like rotations of the small 30S subunit
      relative to the large 50S subunit. Furthermore, our finding indicates a two-step
      mechanism of translocation: first, relative rotation of the subunits and opening
      of the mRNA channel following binding of GTP to EF-G; and second, advance of the
      mRNA/(tRNA)2 complex in the direction of the rotation of the 30S subunit,
      following GTP hydrolysis.

PMID- 10917536
TI  - Mimicry of ice structure by surface hydroxyls and water of a beta-helix
      antifreeze protein.
AB  - Insect antifreeze proteins (AFP) are much more effective than fish AFPs at
      depressing solution freezing points by ice-growth inhibition. AFP from the beetle
      Tenebrio molitor is a small protein (8.4 kDa) composed of tandem 12-residue
      repeats (TCTxSxxCxxAx). Here we report its 1.4-A resolution crystal structure,
      showing that this repetitive sequence translates into an exceptionally regular
      beta-helix. Not only are the 12-amino-acid loops almost identical in the
      backbone, but also the conserved side chains are positioned in essentially
      identical orientations, making this AFP perhaps the most regular protein
      structure yet observed. The protein has almost no hydrophobic core but is
      stabilized by numerous disulphide and hydrogen bonds. On the conserved side of
      the protein, threonine-cysteine-threonine motifs are arrayed to form a flat beta
      sheet, the putative ice-binding surface. The threonine side chains have exactly
      the same rotameric conformation and the spacing between OH groups is a near
      perfect match to the ice lattice. Together with tightly bound co-planar external
      water, three ranks of oxygen atoms form a two-dimensional array, mimicking an ice
      section.

PMID- 10917537
TI  - Beta-helix structure and ice-binding properties of a hyperactive antifreeze
      protein from an insect.
AB  - Insect antifreeze proteins (AFP) are considerably more active at inhibiting ice
      crystal growth than AFP from fish or plants. Several insect AFPs, also known as
      thermal hysteresis proteins, have been cloned and expressed. Their maximum
      activity is 3-4 times that of fish AFPs and they are 10-100 times more effective
      at micromolar concentrations. Here we report the solution structure of spruce
      budworm (Choristoneura fumiferana) AFP and characterize its ice-binding
      properties. The 9-kDa AFP is a beta-helix with a triangular cross-section and
      rectangular sides that form stacked parallel beta-sheets; a fold which is
      distinct from the three known fish AFP structures. The ice-binding side contains
      9 of the 14 surface-accessible threonines organized in a regular array of TXT
      motifs that match the ice lattice on both prism and basal planes. In support of
      this model, ice crystal morphology and ice-etching experiments are consistent
      with AFP binding to both of these planes and thus may explain the greater
      activity of the spruce budworm antifreeze.

PMID- 10917538
TI  - Changes in 18F-FDG uptake measured by PET as a pharmacodynamic end-point in
      anticancer therapy. How far have we got?

PMID- 10917539
TI  - Progress in establishing non-surgical oncology within English cancer units.
AB  - In 1995 the Department of Health recommended a minimum standard of five non
      surgical oncology sessions per week at Cancer Units. Postal surveys of cancer
      units in England were conducted in 1996 and 1999 to establish the level of
      provision. Substantial progress has been made from 20-60% of responding units
      meeting the minimum standard.

PMID- 10917541
TI  - United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) Strategy Group
      Workshop--'Clinical endpoints in trials of biological agents'.

PMID- 10917540
TI  - FDG-PET in the prediction of survival of patients with cancer of the pancreas: a
      pilot study.
AB  - Carcinoma of the pancreas is an aggressive tumour with an extremely poor
      prognosis. Recent studies have shown that chemotherapy can improve survival as
      well as quality of life. Since the prognosis is generally poor, the
      identification of early responders to chemotherapy is important to avoid
      unnecessary toxicity in patients who are not responding. Response assessment by
      conventional radiographic methods is problematical because treatment induces
      fibrosis and makes tumour measurements difficult. The aim of this pilot study was
      to assess 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) as an
      early marker of the benefit of chemotherapy. Eleven patients with histologically
      proven adenocarcinoma of the pancreas were treated with protracted venous
      infusional 5-fluorouracil (PVI 5-FU) alone or PVI 5-FU and mitomycin C (MMC). FDG
      PET scans were performed prior to and at 1 month following the commencement of
      chemotherapy. FDG uptake was compared with the tumour dimensions measured on a
      computer tomographic (CT) scan. Patients were followed up for relapse, death and
      symptomatic response. Three of the 11 patients had no measurable FDG uptake prior
      to chemotherapy. Of the eight patients who had measurable uptake prior to
      treatment, seven had a reduction in uptake at 1 month. Six out of the 11 patients
      had no measurable FDG uptake at 1 month. The overall survival (OS) in these
      patients ranged from 124 to 1460 days, with a median of 318.5 days. This was
      superior in comparison to patients who had residual FDG uptake at 1 month (median
      survival 318.5 days vs 139 days; P = 0.034) and there was a trend to improved
      symptoms (84% [5/6] vs 20% [1/5]; P = 0.13). There was no statistically
      significant correlation between best CT response and FDG uptake at 1 month. These
      results suggest that the absence of FDG uptake at 1 month following chemotherapy
      for carcinoma of the pancreas is an indicator of improved overall survival. This
      suggests that FDG-PET may be superior to response assessment by conventional
      radiographic methods and FDG-PET may have the potential to help make difficult
      treatment decisions in the management of pancreatic cancer. Larger prospective
      studies are required to confirm this finding.

PMID- 10917542
TI  - Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through
      the urokinase plasminogen activator receptor.
AB  - We have previously shown that platelet-produced thrombospondin-1 up-regulates the
      urokinase plasminogen activator and its receptor and promotes tumour cell
      invasion. Although tumour cells produce thrombospondin-1 in vivo, they produce
      only minimal amounts of thrombospondin-1 in vitro. To determine the effect of
      tumour cell-produced thrombospondin-1 in the regulation of the
      plasminogen/plasmin system and tumour cell invasion, we studied THBS-1
      transfected MDA-MB-435 breast cancer cells that overexpress thrombospondin-1. The
      role of urokinase plasminogen receptor in thrombospondin-1-mediated adhesion and
      invasion was studied by antisense inhibition, enzymatic cleavage and antibody
      neutralization. Tumour cell adhesion to collagen and laminin was evaluated.
      Tumour cell invasion was studied in a modified Boyden chamber collagen invasion
      assay. Tumour cell thrombospondin-1 induced a 2-7 fold increase in urokinase
      plasminogen activator receptor and cell-associated urokinase plasminogen
      activator expression and a 50-65% increase in cell-associated urokinase
      plasminogen activator and plasmin activities. Furthermore, tumour cell
      thrombospondin-1 promoted tumour cell invasion and decreased tumour cell adhesion
      through up-regulation of urokinase plasminogen activator receptor-controlled
      urokinase plasminogen activator and plasmin activities. We conclude that tumour
      cell-produced thrombospondin-1 may play a critical role in the regulation of
      tumour cell adhesion and tumour cell invasion.

PMID- 10917543
TI  - Uneven distribution of HPV 16 E6 prototype and variant (L83V) oncoprotein in
      cervical neoplastic lesions.
AB  - A previous Swedish study revealed that both prototype and variant HPV16 E6
      oncoprotein, occur in about equal numbers in high-grade cervical intraepithelial
      neoplasia (HCIN), whereas variant HPV16 predominates in invasive cervical
      squamous carcinoma. Most of the malignant HPV16 variants contain a common
      mutation, L83V, in the E6 oncoprotein. In the present investigation, 28 HPV16
      positive, invasive cervical adenocarcinomas were collected from a total number of
      131 adenocarcinomas. These HPV16-positive cases were evaluated with analysis of
      the E6 gene, using a recently described PCR-SSCP method for identification of the
      specific mutation (L83V) in the E6 gene. The results obtained were correlated to
      findings in 103 preinvasive, HCIN, and 31 invasive cervical squamous carcinomas
      also infected with HPV16. The HPV16 E6 variant L83V was present in 40% of the
      HCIN lesions, in 54% of the invasive adenocarcinomas, in comparison to 81% of the
      invasive squamous carcinomas. The difference between HCIN and squamous carcinomas
      was statistically significant, P < 0.001, whereas the difference between HCIN and
      invasive adenocarcinomas was not statistically significant, P = 0.604. Prototype
      HPV16 and its E6 variant L83V are both prevalent in preinvasive and invasive
      cervical lesions in Swedish women. However, the obvious predominance of HPV16
      variant in squamous carcinomas was not seen in adenocarcinomas. A single amino
      acid shift in the HPV16 E6 gene appears to result in a different transforming
      potential in squamous and glandular cervical lesions.

PMID- 10917544
TI  - Correlation of oncoprotein 18/stathmin expression in human breast cancer with
      established prognostic factors.
AB  - Oncoprotein 18/stathmin (Op18) is a conserved cytosolic phosphoprotein that
      regulates microtubule dynamics. The microtubule destabilizing activity is
      regulated by phosphorylation, mediated by both growth factor stimulated- and cell
      cycle regulating kinases. The protein is highly expressed in a variety of human
      malignancies. In human breast carcinoma, Op18 has previously been shown to be up
      regulated in a subset of the tumours, however, no correlation with
      clinicopathologic characteristics has been reported so far. In the present study
      we have examined Op18 protein expression by quantitative Western blot analysis in
      a panel of 151 semi-consecutive breast carcinoma samples. Op18 levels were
      negatively correlated with oestrogen receptor (OR) expression and positively
      correlated with a high fraction of aneuploid cells, proliferation measured by
      proliferating cell nuclear antigen (PCNA) expression, tumour size and
      histopathologic grade. Taken together, and in contrast to what has been
      previously reported, the present study shows that high Op18 expression correlates
      with general predictive factors and is not restricted to a specific sub-group of
      breast carcinoma.

PMID- 10917545
TI  - Metallothionein 1E mRNA is highly expressed in oestrogen receptor-negative human
      invasive ductal breast cancer.
AB  - Metallothioneins (MTs), a group of ubiquitous metalloproteins, comprise isoforms
      encoded by ten functional genes in humans. Different MT isoforms possibly play
      different functional roles during development or under various physiological
      conditions. The MT-1E isoform mRNA has been recently shown to be differentially
      expressed in oestrogen receptor (OR)-positive and OR-negative breast cancer cell
      lines. In this study, we evaluated MT-1E mRNA expression via semi-quantitative RT
      PCR in 51 primary invasive ductal breast cancer tissues, concurrently with OR
      positive and progesterone receptor (PR)-positive MCF7 cells, OR-negative and PR
      negative MDA-MB-231 cells and PR-transfected MDA-MB-231 breast cancer cells
      (ABC28). We demonstrated significantly higher MT-1E mRNA expression in OR
      negative compared with OR-positive breast cancer tissues (P = 0.026). MCF7 cells
      lacked MT-1E mRNA expression, while both OR- and PR-negative MDA-MD-231 cells
      exhibited a high level of MT-1E mRNA expression. The level of MT-1E mRNA
      expression in progesterone-treated and -untreated ABC28 cells remained similar as
      the parental cell line MDA-MB-231-C2 cells. The results suggest that MT-1E may
      have specific and functional roles in OR-negative invasive ductal breast cancers,
      possibly mediated via effector genes downstream of the oestrogen receptor, but
      not through the PR pathway.

PMID- 10917546
TI  - Cyclooxygenase-2 overexpression correlates with tumour recurrence, especially
      haematogenous metastasis, of colorectal cancer.
AB  - Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory
      drugs (NSAIDs), known to inhibit cyclooxygenase (COX), reduce the risk of
      colorectal cancer. COX is a key enzyme in prostaglandin biosynthesis, and two
      isoforms of COX, COX-1 and COX-2, have been identified. Recently COX-2 has been
      reported to frequently overexpress in colorectal neoplasms and to play a role in
      colorectal tumorigenesis and tumour progression. In this study, using
      immunohistochemistry, we examined COX-2 expression in advanced human colorectal
      cancer and its correlation with clinicopathological features. COX-2 expression
      was observed mainly in the cytoplasm of cancer cells in all the specimens
      examined, but some stromal cells and endothelial cells were also stained.
      According to the grade of COX-2 expression of the cancer cells, patients were
      divided into high- and low-COX-2 expression groups. High-COX-2 expression
      significantly correlated with tumour recurrence, especially haematogenous
      metastasis. These results suggest that a selective COX-2 inhibitor can be a novel
      class of therapeutic agents not only for tumorigenesis but also for haematogenous
      metastasis of colorectal cancer. To our knowledge, this is the first report on
      the correlation between COX-2 overexpression and recurrence of colorectal cancer.

PMID- 10917547
TI  - Specific oncolytic activity of herpesvirus saimiri in pancreatic cancer cells.
AB  - The potential use of oncolytic viruses in the treatment of cancer has been
      investigated for some time. A variety of agents have been studied, including some
      which appear to be selectively replication-competent in cancer cell lines. In
      this study, we have investigated the ability of herpesvirus saimiri to
      specifically lyse selected human cancer cell lines. Upon infection with a
      replication-competent virus carrying the EGFP reporter gene and a neomycin
      resistance marker, the pancreatic cancer lines MIAPACA and PANC-1 exhibited
      definite cytopathic effects. In contrast, the colonic carcinoma cell lines SW480
      and HCT116 were phenotypically unaltered. In addition, stable cell lines could
      not be generated from PANC-1 infected cultures, in marked contrast to cultures of
      cells from other human tissues. Virus recovery assays demonstrated that all of
      the cell lines produced a small amount of virus post-infection, but that virus
      replication was minimal after 1 week in culture. In addition, treatment with
      acyclovir inhibited virus replication but paradoxically increased cytopathic
      effect. These data suggest that herpesvirus saimiri may have potential as an
      oncolytic agent for the treatment of pancreatic cancer.

PMID- 10917548
TI  - Inhibition of aromatase activity and expression in MCF-7 cells by the
      chemopreventive retinoid N-(4-hydroxy-phenyl)-retinamide.
AB  - The effect of the chemopreventive synthetic retinoid N-(4-hydroxyphenyl)
      retinamide (4-HPR) on aromatase activity and expression was examined. 4-HPR
      caused a dose-dependent inhibition of aromatase activity in microsomes isolated
      from JEG-3 human placental carcinoma cells. The kinetics of inhibition were
      analysed by double-reciprocal plot. The Km of the substrate increased and the
      Vmax of the reaction decreased in the presence of 4-HPR, indicating that enzyme
      inhibition involved both competition for the substrate-binding site and non
      competitive mechanisms. To determine whether 4-HPR would also inhibit aromatase
      activity in intact cells, MCF-7 human breast cancer cells were incubated with or
      without cAMP in the presence of 4-HPR. 4-HPR inhibited both basal and cAMP
      induced aromatase activity in intact MCF-7 cells. The induction of aromatase mRNA
      expression in MCF-7 cells by cAMP was inhibited in cells treated with 4-HPR.
      These results indicate that 4-HPR inhibits both the enzymatic activity and
      expression of aromatase. These activities may play an important role in the known
      chemopreventive effect of 4-HPR towards breast cancer.

PMID- 10917549
TI  - Characterization and modulation of drug resistance of human paediatric
      rhabdomyosarcoma cell lines.
AB  - The role of multidrug resistance (MDR) and p53 functional status in the treatment
      of paediatric rhabdomyosarcoma is unclear. We have characterized a panel of seven
      human rhabdomyosarcoma cell lines for MDR and p53 phenotype. None of the cell
      lines had P-glycoprotein (P-gp) or multidrug resistance-related protein (MRP)
      detectable by Western blotting, whereas immunohistochemistry suggested that very
      low levels of MDR proteins may be present in some of the lines. RT-PCR studies
      indicated that mdr-1, mrp-1 and Irp mRNA was present in 5/7, 7/7 and 5/7 lines
      respectively. The function of p53 is compromised in six of the lines, either
      through mutation of the p53 gene or by overexpression of mdm-2. The sensitivity
      of many of the cell lines to vincristine could be modulated above 2-fold and as
      high as 16-fold using two modulating agents, PSC833 and VX710 (with VX710 being a
      significantly more potent modulator of the rhabdomyosarcoma lines). PSC833 also
      increased vincristine accumulation in all of the lines from 1.2- to 2.2-fold.
      These results suggest that some of these cell lines have low levels of multidrug
      resistance. The level of MDR proteins is very low and therefore difficult to
      detect, but may be sufficient to confer low-level, but clinically relevant,
      resistance to some cytotoxic agents, especially vincristine. These cell lines
      will therefore provide a suitable model to test new strategies in treatment and
      for further understanding relationships between protein expression and drug
      resistance.

PMID- 10917550
TI  - Caffeine does not cause override of the G2/M block induced by UVc or gamma
      radiation in normal human skin fibroblasts.
AB  - Caffeine has for many years been known to be involved in the sensitization of DNA
      to damage. One potential mechanism recently put forward is an override of the
      G2/M block induced by irradiation, which would leave the cells less time for DNA
      repair prior to mitosis. However, different cell types display a variety of
      responses and no clear pathway has yet emerged, especially as little is known
      about the capacity of this agent to enhance DNA damage in normal, untransformed
      cells. Continuous exposure to commonly used caffeine concentrations (1-5 mM)
      inhibited the proliferation of normal human fibroblasts (NHFs) in a dose
      dependent manner to up to 80% at 5 mM. Exposure of exponentially growing NHFs to
      UVc radiation (20 J m(-2)) or gamma radiation (2.5-8 Gy) led to a 45-60%
      inhibition of proliferation and protracted accumulation of cells in the G2/M
      phase. Addition of 2 mM caffeine after irradiation induced slowing of the S phase
      passage, with a resultant delay in G2/M accumulation mimicking a G2/M block
      override. These results were confirmed by stathmokinetic studies, which showed
      delayed entry of the cells into mitosis in the presence of caffeine. Our data
      demonstrate that caffeine primarily inhibits replicative DNA synthesis and
      suggest that, at least in normal cells, caffeine potentiates the cytotoxicity of
      radiation by intervening in DNA repair rather than by overriding the G2/M block.

PMID- 10917551
TI  - Hypoxia-induced treatment failure in advanced squamous cell carcinoma of the
      uterine cervix is primarily due to hypoxia-induced radiation resistance rather
      than hypoxia-induced metastasis.
AB  - Poor outcome of treatment in advanced cervix carcinoma has been shown to be
      associated with poor oxygenation of the primary tumour. Hypoxia may cause
      radiation resistance and promote lymph-node metastasis. The purpose of the study
      reported here was to investigate whether hypoxia-induced treatment failure in
      advanced cervix carcinoma is primarily a result of hypoxia-induced radiation
      resistance or the presence of hypoxia-induced lymph-node metastases at the start
      of treatment. Thirty-two patients with squamous cell carcinoma of the uterine
      cervix were included in the study. Radiation therapy was given with curative
      intent as combined external irradiation and endocavitary brachytherapy. The
      oxygenation status of the primary tumour was measured prior to treatment using
      the Eppendorf PO2 Histograph. Pelvic and para-aortal lymph-node metastases were
      detected by magnetic resonance imaging at the time of initial diagnosis. The
      primary tumours of the patients with metastases (n = 18) were significantly more
      poorly oxygenated than those of the patients without metastases (n = 14).
      Multivariate Cox regression analyses involving biological and clinical parameters
      identified the tumour subvolume having PO2 values below 5 mmHg (HSV (pO2 < 5
      mmHg) as the only significant, independent prognostic factor for locoregional
      control, disease-free survival and overall survival. The probabilities of
      locoregional control, disease-free survival and overall survival were
      significantly lower for the patients with HSV (PO2 < 5 mmHg) above the median
      value than for those with HSV (PO2 < 5 mmHg) below the median value. On the other
      hand, the outcome of treatment was not significantly different for the patients
      with metastases and the patients without metastases at the start of treatment,
      irrespective of clinical end-point. Consequently, treatment failure was primarily
      a result of hypoxia-induced radiation resistance rather than hypoxia-induced
      lymph-node metastasis, suggesting that novel treatment strategies aiming at
      improving tumour oxygenation or enhancing the radiation sensitivity of hypoxic
      tumour cells may prove beneficial in attempts to improve the radiation therapy of
      advanced cervix carcinoma.

PMID- 10917552
TI  - Endothelin-1 from prostate cancer cells is enhanced by bone contact which blocks
      osteoclastic bone resorption.
AB  - The causes for the propensity of metastasized prostate cancer cells to grow in
      bone and to induce osteoblastic lesions remain unresolved. Co-culture of human
      prostate cancer cell lines with bone slices was determined to increase the level
      of endothelin-1 (ET-1) mRNA and its production. ET-1 is an ejaculate protein that
      also stimulates osteoblasts. Osteoclastic bone resorption was significantly
      blocked by the presence of androgen-independent prostate cancer cells in a dose
      dependent manner as that of synthetic ET-1. The inhibition could be neutralized
      by specific ET-1 antibody, indicating the association of prostate cancer-derived
      ET-1 with inhibition of bone resorption. The combined ET-1 activity on
      osteoclasts and osteoblasts disrupts bone remodelling. ET-1 production is also
      elevated in the presence of prostate-specific antigen (PSA). ET-1 in turn
      enhances DNA synthesis of prostate cancer cells. Interactions among cancer cells,
      bone, ET-1 and PSA may be critical in cancer growth and lesions in bone.

PMID- 10917553
TI  - Inhibitory effect of the reversal agents V-104, GF120918 and Pluronic L61 on MDR1
      Pgp-, MRP1- and MRP2-mediated transport.
AB  - The human multidrug transporter MDR1 P-glycoprotein and the multidrug resistance
      proteins MRP1 and MRP2 transport a range of cytotoxic drugs, resulting in
      multidrug resistance in tumour cells. To overcome this form of drug resistance in
      patients, several inhibitors (reversal agents) of these transporters have been
      isolated. Using polarized cell lines stably expressing human MDR1, MRP1 or
      MRP2cDNA, and 2008 ovarian carcinoma cells stably expressing MRP1 cDNA, we have
      investigated in this study the specificity of the reversal agents V-104 (a
      pipecolinate derivative), GF120918 (an acridone carboxamide derivative also known
      as GG918), and Pluronic L61 (a (poly)oxypropethylene and (poly)oxypropylene block
      copolymer). Transport experiments with cytotoxic drugs with polarized cell lines
      indicate that all three compounds efficiently inhibit MDR1 Pgp. Furthermore, V
      104 partially inhibits daunorubicin transport by MRP1 but not vinblastine
      transport by MRP2. V-104 reverses etoposide resistance of 2008/MRP1 cells,
      whereas GF120918 does not reverse resistance due to MRP1. V-104 partially
      inhibits the export of the organic anion dinitrophenyl S-glutathione by MDCKII
      MRP1 but not by MDCKII-MRP2 cells. Unexpectedly, export of the organic anion
      calcein by MDCKII-MRP1 and MDCKII-MRP2 cells is stimulated by Pluronic L61,
      probably because it relieves the block on entry of calcein AM into the cell by
      endogenous MDR1 Pgp.

PMID- 10917554
TI  - Vinblastine and sulfinpyrazone export by the multidrug resistance protein MRP2 is
      associated with glutathione export.
AB  - The multidrug resistance proteins MRP1 and MRP2 are members of the same subfamily
      of ATP-binding cassette transporters. Besides organic molecules conjugated to
      negatively charged ligands, these proteins also transport cytotoxic drugs for
      which no negatively charged conjugates are known to exist. In polarized MDCKII
      cells, MRP1 routes to the lateral plasma membrane, and MRP2 to the apical plasma
      membrane. In these cells MRP1 transports daunorubicin, and MRP2 vinblastine; both
      transporters export reduced glutathione (GSH) into the medium. We demonstrate
      that glutathione transport in MDCKII-MRP1 cells is inhibited by the inhibitors of
      organic anion transporters sulfinpyrazone, indomethacin, probenecid and
      benzbromarone. In MDCKII-MRP2 cells, GSH export is stimulated by low
      concentrations of sulfinpyrazone or indomethacin, whereas export is inhibited
      down to control levels at high concentrations. We find that unmodified
      sulfinpyrazone is a substrate for MRP2, also at concentrations where GSH export
      is inhibited. We also show that GSH export in MDCKII-MRP2 cells increases in the
      presence of vinblastine, and that the stoichiometry between drug and GSH exported
      is between two and three. Our data indicate that transport of sulfinpyrazone and
      vinblastine is associated with GSH export. However, at high sulfinpyrazone
      concentrations this compound is transported without GSH. Models of MRP action are
      discussed that could explain these results.

PMID- 10917555
TI  - Contralateral breast cancer risk is influenced by the age at onset in BRCA1
      associated breast cancer.
AB  - BRCA1/2 mutation carriers diagnosed with breast cancer have a strongly elevated
      life-time risk of developing a contralateral tumour. We studied the contralateral
      breast cancer risk in 164 patients from 83 families with a proven BRCA1 mutation
      in relation to the age at diagnosis of the first primary breast cancer. In the
      actuarial outcomes after 10 years' follow-up, 40% of the 124 BRCA1-patients
      diagnosed with breast cancer < 50 years had developed contralateral breast
      cancer, vs 12% of the 40 patients > 50 years at first diagnosis (Plogrank =
      0.02). These data suggest that age at diagnosis of the first tumour should be
      taken into account when prophylactic mastectomy in BRCA1-patients is considered.

PMID- 10917556
TI  - Socioeconomic status and risk of adenocarcinoma of the oesophagus and cancer of
      the gastric cardia in Scotland.
AB  - The incidence of oesophageal adenocarcinoma and gastric cardia cancer increased
      strikingly in Scotland between 1977 and 1996. In contrast to other cancers of the
      oesophagus and stomach, which showed a clear relationship with socioeconomic
      status, no trend was evident for oesophageal adenocarcinoma or gastric cardia
      cancer during 1987-1996.

PMID- 10917557
TI  - Decreasing incidence of both major histologic subtypes of gastric adenocarcinoma-
      a population-based study in Sweden.
AB  - While the overall incidence of gastric cancer has fallen, presumably to a large
      extent in parallel with Helicobacter pylori infection, the occurrence of the
      diffuse histologic type is thought to have remained more stable, questioning the
      aetiologic role of H. pylori. We have analysed the incidence of the intestinal
      and diffuse types separately, while considering subsite (cardia/non-cardia). With
      an extensive prospective effort we identified all incident cases of gastric
      adenocarcinoma (n = 1337) in a well-defined Swedish population (1.3 million) 1989
      1994. Tumours were uniformly classified histologically and topographically.
      Subgroup-specific incidence rates were computed and modelled using multivariate
      logistic regression. Site-specific trends were clearly discrepant. The overall
      incidence of adenocarcinoma distal to the gastric cardia declined by 9% (95%
      confidence interval 6-12%) per year, while cardia cancer remained stable. Thus,
      the feared rise in cardia cancer could not be confirmed despite clear site
      specific trend discrepancies. The intestinal type predominated, especially in
      high-risk areas, while diffuse tumours prevailed among young patients and women.
      Both main histologic types of gastric adenocarcinoma declined markedly, at
      similar rapidity, and with no significant trend differences between the
      intestinal and diffuse types, even after multivariate adjustments. Our results
      are consistent with an aetiologic role of environmental factors including H.
      pylori also for diffuse-type gastric cancers.

PMID- 10917558
TI  - Incidence and survival for cancer in children and young adults in the North of
      England, 1968-1995: a report from the Northern Region Young Persons' Malignant
      Disease Registry.
AB  - The Northern Region Young Persons' Malignant Disease Registry records information
      on young people under 25 years old diagnosed with cancer in the Northern Region
      of England. Incidence and survival rates were calculated for children and young
      adults diagnosed with cancer between 1968 and 1995. There were 2099 (M:F 1.28:1)
      children (age 0-14 years) and 2217 (M:F 1.23:1) young adults (15-24 years)
      diagnosed with a first cancer between 1968 and 1995. The age-standardized rate
      (ASR) for childhood cancer was 121 per million 0 to 14 year-olds per year. For
      young adults the ASR was 175 per million 15 to 24 year-olds, per year. Incidence
      of childhood cancer increased over time at a rate of 12 extra cases per million
      children, per decade (P < 0.001). In young adults incidence rates increased by 16
      extra cases per million 15 to 24 year-olds, per decade (P < 0.001). For childhood
      cancer 5-year survival was 42% for those diagnosed 1968-1977, 57% for 1978-1987
      and 71% (95% CI 67-75) for 1988-1995. Survival for young adults over the three
      periods was 45%, 62% and 73% (95% CI 70-78) respectively. The cumulative risk of
      developing cancer before the age of 25 is 1 in 285. Over the 28-year period there
      were significant improvements in survival and modest increases in incidence in
      both children and young adults.

PMID- 10917559
TI  - Risk of ovarian cancer in relation to use of phenolphthalein-containing
      laxatives.
AB  - We examined ovarian cancer risk in relation to use of phenolphthalein-containing
      laxatives in 410 epithelial ovarian cancer cases and 713 controls. Compared to
      women who never used a laxative, ever use of a phenolphthalein-containing
      laxative was not associated with an increased risk of ovarian cancer (odds ratio,
      OR, 1.1, 95% confidence interval, CI, 0.9-1.4). Risk was slightly, but not
      significantly, higher with more frequent use (OR 1.2 for 75 or more days of use).
      When women who used non-phenolphthalein containing laxatives was used as the
      reference group, the associations were slightly, but not significantly larger (OR
      1.4 for any use of phenolphthalein-containing laxatives and OR 1.5 for 75 or more
      days of use)

PMID- 10917560
TI  - Cancers in the first-degree relatives of children with brain tumours.
AB  - We used the nationwide Swedish Family-Cancer Database with 2060 childhood brain
      tumours diagnosed in the period 1958-1996 to analyse the risk of this tumour by
      parental cancers and in siblings of childhood brain tumour probands. Groups of
      patients were compared by calculating standardized incidence ratios (SIRs) for
      brain tumours in offspring. 1.3% of brain tumour patients had a parent with
      nervous system cancer; SIRs were 2.4 and 1.88 for diagnostic ages < 5 and < 15
      years, respectively. The data showed distinct patterns of familial risks for
      childhood brain tumours, the SIR was 10.26 for brain astrocytoma given a parent
      with meningioma. Parental colon cancer was associated with offspring ependymoma
      (SIR 3.70), and parental salivary gland cancers with offspring medulloblastoma
      (SIR 13.33, but two cases only). SIR for sibling nervous system cancer from
      childhood brain tumour probands was 3.55 up to age 61.

PMID- 10917562
TI  - Ascorbic acid induces spectrin reorganization in bull epididymal spermatozoa.
AB  - The acrosome, a complex organelle, plays a key regulatory role in the sperm-egg
      interaction. We have previously shown that ascorbic acid affects both motility
      and spectrin protein patterns in sperm. In this study, we further characterized
      the changes in spectrin in sperm challenged with ascorbic acid, using SDS-PAGE,
      western blots, and immunofluorescence. Ascorbic acid shifts spectrin to a higher
      molecular-weight species based on western blot studies. This shift in the
      spectrin band correlates with a striking series of changes in spectrin
      immunofluorescence patterns. Upon ascorbic acid challenge, spectrin localization
      changes, eventually resulting in the formation of vesicles. These vesicles can
      reach sizes up to five times the original volume of the sperm cell and sometimes
      show multiple spikes. These findings indicate that a novel process is taking
      place in the acrosome upon ascorbic acid challenge and suggest that the
      cytoskeleton may be a useful target for studying and hopefully controlling the
      sperm-egg interaction.

PMID- 10917561
TI  - N-acetyltransferase 2 and bladder cancer: an overview and consideration of the
      evidence for gene-environment interaction.
AB  - Genetic polymorphism of the carcinogen metabolizing enzyme N-acetyl transferase 2
      (NAT2) may influence susceptibility to bladder cancers related to smoking or to
      occupational exposure to arylamine carcinogens. This article reviews the results
      of 21 published case-control studies of NAT2 polymorphism and bladder-cancer
      risk, with a total of 2700 cases and 3426 controls. The published evidence
      suggests that NAT2 slow acetylator phenotype or genotype may be associated with a
      small increase in bladder cancer risk. However, given the possibility of
      selective publication of results from studies that found an excess risk, the
      current evidence is not sufficient to conclude that there is a real increase in
      risk. Only five of the 21 studies reported results separately for the effect of
      NAT2 on bladder cancer risk in smokers and non-smokers. Although the results
      suggest that the effect may be greater in smokers than in non-smokers, the
      possibility of publication bias makes these results difficult to interpret. There
      was insufficient evidence to assess the joint effect of NAT2 and occupational
      exposure to arylamines on bladder cancer risk. Even if estimates of the effect of
      NAT2 from published data are correct, studies with around 3000-5000 cases will be
      needed to confirm them.

PMID- 10917563
TI  - Antioxidant activity and protective effect on DNA cleavage of extracts from
      Cistus incanus L. and Cistus monspeliensis L.
AB  - The genus Cistus includes many typical species of Mediterranean flora; Cistus
      species are used as antidiarrhetics, as general remedies for treatment of various
      skin diseases in folk medicine and as anti-inflammatory agents. These species
      contain flavonoids that are considered to be chain-breaking antioxidants. In this
      work, we have investigated the effects of crude aqueous extracts from Cistus
      incanus and Cistus monspeliensis on DNA cleavage and their free-radical
      scavenging capacity. In addition, their effect on lipid peroxidation in rat liver
      microsomes was evaluated. These extracts showed a protective effect on DNA
      cleavage and a dose-dependent free-radical scavenging capacity; Cistus
      monspeliensis was more active than Cistus incanus; these results were confirmed
      by a significant inhibition of lipid peroxidation in rat liver microsomes. The
      experimental evidence, therefore, suggests that because of their antioxidant
      activity these extracts may offer excellent photoprotection for skin and may be
      useful in the treatment of human diseases where oxidative stress plays a key
      role.

PMID- 10917564
TI  - Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors.
AB  - Flavonoids have recently aroused considerable interest because of their broad
      pharmacological activity. In fact, flavonoids have been reported to have
      antiviral, antiallergic, antiplatelet, anti-inflammatory and antitumoral
      activities. The pharmacological properties of bioflavonoids have been ascribed
      both to the concomitant inhibition of enzymes involved in the production of free
      radicals and to their free-radical scavenging and iron chelating capacity.
      However the antioxidant capacity of bioflavonoids due to free-radical scavenging
      and/or to iron chelating is still controversial. In this study, we have
      investigated the free-radical scavenging capacity of bioflavonoids (rutin,
      catechin, and naringin). In addition, the effects of these polyphenols on
      xanthine oxidase activity, spontaneous lipid peroxidation, and DNA cleavage were
      investigated. The bioflavonoids under examination showed a dose-dependent free
      radical scavenging effect, a significant inhibition of xanthine oxidase activity,
      and an antilipoperoxidative capacity. In addition, they showed a protective
      effect on DNA cleavage.

PMID- 10917565
TI  - L -propionyl-carnitine as superoxide scavenger, antioxidant, and DNA cleavage
      protector.
AB  - L-Propionylcarnitine, a propionyl ester of L-carnitine, increases the
      intracellular pool of L-carnitine. It exhibits a high affinity for the enzyme
      carnitine acetyltransferase (CAT) and, thus, is readily converted into propionyl
      coenzyme A and free carnitine. It has been reported that L-propionylcarnitine
      possesses a protective action against heart ischemia-reperfusion injury; however,
      the antioxidant mechanism is not yet clear. L-Propionylcarnitine might reduce the
      hydroxyl radical production in the Fenton system, by chelating the iron required
      for the generation of hydroxyl radicals. To obtain a better insight into the
      antiradical mechanism of L-propionylcarnitine, the present research analyzed the
      superoxide scavenging capacity of L-propionylcarnitine and its effect on linoleic
      acid peroxidation. In addition, the effect of L-propionylcarnitine against DNA
      cleavage was estimated using pBR322 plasmid. We found that L-propionylcarnitine
      showed a dose-dependent free-radical scavenging activity. In fact, it was able to
      scavenge superoxide anion, to inhibit the lipoperoxidation of linoleic acid, and
      to protect pBR322 DNA from cleavage induced by H2O2 UV-photolysis.

PMID- 10917566
TI  - Viability and drug metabolism capacity of alginate-entrapped hepatocytes after
      cryopreservation.
AB  - In the present study we evaluated viability and detoxifying enzyme capacity of
      cryopreserved hepatocytes from various species, including man, immobilized in
      calcium alginate gels. Ethoxyresorufin O-deethylase, phenacetin deethylase,
      pentoxyresorufin O-dealkylase, tolbutamide hydroxylase, S-mephenytoin
      hydroxylase, dextromethorphan demethylase, and nifedipine oxidation corresponding
      to the major cytochromes P450 (CYP) involved in xenobiotic metabolism as well as
      whole glutathione S-transferase (GST) activity were measured using specific
      substrates and after exposure or not to prototypical inducers. After deep-freeze
      storage, viability of immobilized hepatocytes was only slightly reduced and most
      CYP-related monooxygenase activities were well preserved, being expressed at
      levels close to those measured in unfrozen hepatocyte monolayers. By contrast,
      total GST activity was decreased by around 50%. However, as did CYP1A- and 3A
      related enzymes, rat GST remained capable of responding to prototypical inducers.
      The fold increases were comparable in unfrozen and frozen immobilized hepatocytes
      and in unfrozen hepatocyte monolayers. The duration of storage, even when
      exceeding one year, did not affect viability and functions. In conclusion, after
      cryopreservation, alginate-entrapped hepatocytes remain highly viable and capable
      of expressing most detoxifying enzymes at levels close to those expressed in
      corresponding unfrozen hepatocyte monolayers and of responding to prototypical
      inducers.

PMID- 10917567
TI  - Spermine cytotoxicity to human colon carcinoma-derived cells (CaCo-2).
AB  - Spermine is a constituent of all vertebrate cells. Nevertheless, it exerts toxic
      effects if it accumulates in cells. Spermine is a natural substrate of the FAD
      dependent polyamine oxidase, a constitutive enzyme of many cell types. It has
      been reported that the toxicity of spermine was enhanced if polyamine oxidase was
      inhibited. We were interested to examine spermine toxicity to human colon
      carcinoma-derived CaCo-2 cells because, in contrast to most tumor cell lines,
      CaCo-2 cells undergo differentiation, which is paralleled by changes in polyamine
      metabolism. CaCo-2 cells were remarkably resistant to spermine accumulation,
      presumably because spermine is degraded by polyamine oxidase at a rate sufficient
      to provide spermidine for the maintenance of growth. Inactivation of polyamine
      oxidase increased the sensitivity to spermine. A major reason for the enhanced
      spermine cytotoxicity at low polyamine oxidase activity is presumably the
      profound depletion of spermidine, and the consequent occupation of spermidine
      binding sites by spermine. Hydrogen peroxide and the aldehydes 3-aminopropanal
      and 3-acetamidopropanal, the products of polyamine oxidase-catalyzed splitting of
      spermine and N1-acetylspermine, contribute little to spermine cytotoxicity.
      Activation of caspase by spermine was insignificant, and the formation of DNA
      ladders, another indicator of apoptotic cell death, could not be observed. Thus
      it appears that cell death due to excessive accumulation of spermine in CaCo-2
      cells was mainly nonapoptotic. The content of brush border membranes did not
      change between days 6 and 8 after seeding, and it was not affected by exposure of
      the cells to spermine. However, the activities of alkaline phosphatase, sucrase,
      and aminopeptidase in nontreated cells were considerably enhanced during this
      period, but remained low if cells were exposed to spermine. These changes appear
      to indicate that differentiation is prevented by intoxication with spermine,
      although other explanations cannot be excluded.

PMID- 10917568
TI  - The effect of activation of peroxisome proliferator-activated receptor gamma
      (PPARgamma) on human monocyte function: PPARgamma ligands do not inhibit tumor
      necrosis factor-alpha release in human monocytic cell line THP-1.
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) activation by its
      ligands reportedly inhibits monocyte function. However, because the
      concentrations of PPARgamma ligands used in previous studies were higher than
      typically expected to activate PPARgamma, we clarified whether PPARgamma ligands
      influence monocyte function and cell viability of the human monocyte cell line
      THP-1. We determined tumor necrosis factor-alpha (TNF-alpha) release as a
      monocyte function and cell viability using 3-[4,5-dimethylthiazol-2-yl]-2,5
      diphenyltetrazolium bromide. Both troglitazone and 15-deoxy-delta12,14
      prostaglandin J2 (15-d-PGJ2) seemed to inhibit phorbol ester-induced TNF-alpha
      release from THP-1 cells. On the other hand, neither pioglitazone nor
      rosiglitazone inhibited phorbol ester-induced TNF-alpha release. Because the
      cytotoxicity of troglitazone and 15-d-PGJ2 was significantly (p<0.05, Tukey
      Kramer) stronger than that of pioglitazone and rosiglitazone, the inhibition of
      TNF-alpha release seemed to parallel the lack of cell viability. We concluded
      that PPARgamma ligands did not directly inhibit TNF-alpha release in THP-1 cells.

PMID- 10917569
TI  - Intracellular calcium antagonist protects cultured peritoneal macrophages against
      anthrax lethal toxin-induced cytotoxicity.
AB  - The lethal toxin of Bacillus anthracis is central to the pathogenesis of anthrax.
      Using primary cultures of mouse peritoneal macrophages, we have demonstrated that
      intracellular calcium release inhibitors protect against anthrax lethal toxin
      induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly
      reduced by dantrolene, an inhibitor of calcium release from intracellular calcium
      stores. Pretreatment of macrophages with cyclosporin A, which has been shown to
      be a potent inhibitor of calcium release from mitochondria, also protected cells
      against cytotoxicity. These results indicate that calcium release from
      intracellular store may be an essential step for the propagation of anthrax
      lethal toxin-induced cell damage in macrophages. Thus our findings suggest that
      dantrolene, cyclosporin A, and possibly other drugs affecting intracellular
      calcium pools might be effectively preventing the toxicity from anthrax lethal
      toxin.

PMID- 10917570
TI  - Mycobacterial infections in bone marrow transplant recipients.

PMID- 10917571
TI  - Nontuberculous mycobacterial infections in hematopoietic stem cell transplant
      recipients: characteristics of respiratory and catheter-related infections.
AB  - Over a 20-year period, 40 nontuberculous mycobacteria (NTM) were isolated from
      6259 hematopoietic stem cell transplant (HSCT) recipients (0.64%), of which 28
      were considered to have probable or definite infection (0.44%). Only 3 of 15
      lower respiratory isolates obtained by bronchoalveolar lavage (BAL) and/or
      biopsy; (Mycobacterium avium complex [n = 2] and M. gordonae [n = 1]) caused
      definite or probable lower respiratory tract disease, whereas 12 of 15 were
      considered to cause possible lower respiratory tract disease according to Centers
      for Disease Control and Prevention definitions. The median time to diagnosis was
      251 days following HSCT. All 3 patients with definite NTM disease were
      successfully treated with 3 antimicrobials for several months. Twenty-three
      patients had catheter-related infections, including exit site infection (n = 5),
      tunnel infection (n = 7), and catheter-related bacteremia (n = 11). All were
      caused by rapidly growing mycobacteria. The median time to diagnosis was 61 days
      following HSCT. All patients with catheter-related infections were successfully
      treated with an average of 2 antibiotics for a median of 3 weeks for exit site
      infection and 6 weeks for tunnel infection and catheter-related bacteremia. Soft
      tissue debridement was performed in all cases with tunnel infection. The catheter
      was removed in 21 of 23 patients with catheter-related infections. Two additional
      patients were diagnosed, one with lymphadenitis and one with skin lesion, due to
      NTM. In conclusion, NTM infections are infrequent in HSCT recipients and carry a
      good clinical prognosis. In the majority of lower NTM respiratory isolates
      obtained by BAL, a pathogenic role could not be established. However, lower
      respiratory tract disease can occur late after HSCT and should be considered if
      patients fail to respond to the treatment of concomitant infections or if
      evidence of tissue infection or concomitant bacteremia is present. Therapy should
      be performed with 2 to 3 antimicrobials, guided by antimicrobial
      susceptibilities, with additional surgical debridement in patients with tunnel
      infection.

PMID- 10917572
TI  - The frequency of tuberculosis in adult allogeneic stem cell transplant recipients
      in Turkey.
AB  - In general, tuberculosis (Tb) is rarely seen in allogeneic stem cell transplant
      (alloSCT) recipients, but this observation has been challenged in developing
      countries such as Turkey, where Tb infection is more prevalent than in Europe and
      the US. In this retrospective study, we report on the incidence of Tb infections
      in 351 alloSCT recipients at 4 bone marrow transplantation units in Turkey over
      the last 10 years. The frequency of Tb in alloSCT recipients after allografting
      (5 of 351) was far greater than that in the general population (35.4 per
      100,000). Of the 351 patients who underwent alloSCT, 77 who received isoniazid
      (INH) chemoprophylaxis for 6 months did not develop posttransplantation Tb.
      However, 5 of the remaining 274 patients who received no chemoprophylaxis
      developed Tb a median of 12 months (range, 10-47 months) after allografting.
      Antituberculosis therapy resulted in complete recovery in all cases. In 2
      additional patients who were found to have active pulmonary Tb at the time of
      transplantation, alloSCT was delayed until the infections were treated.
      Infections of mycobacteria other than Mycobacterium tuberculosis were not
      observed. The number of patients who received and tolerated INH may not be
      sufficient for firm conclusions, but the data suggest that, in countries where Tb
      is prevalent, pre- and posttransplantation follow-up for Tb and the use of INH
      prophylaxis should be considered.

PMID- 10917573
TI  - Conversion to full donor chimerism following donor lymphocyte infusion is
      associated with disease response in patients with multiple myeloma.
AB  - Donor lymphocyte infusions (DLIs) have been demonstrated to induce clinical
      responses in patients with relapsed multiple myeloma after allogeneic bone marrow
      transplantation, but the immunologic mechanisms involved have not been well
      characterized. In patients with chronic myelocytic leukemia (CML), remissions
      following DLI are invariably associated with conversion to complete donor
      hematopoiesis, suggesting that the target antigens of this response are expressed
      on both normal and CML-derived hematopoietic stem cells. In the present study, we
      examined hematopoietic chimerism and the complexity of the T-cell receptor (TCR)
      repertoire in 4 patients with relapsed multiple myeloma who received infusions of
      donor CD4+ lymphocytes. Three of 4 patients had a clinical response that began 1
      to 2 months after DLI. All 3 responding patients developed lymphocytosis at the
      initiation of response that was due to a 2- to 4.5-fold increase in the number of
      CD3+ T cells. In 1 patient, this was due primarily to increases in CD3+ and CD8+
      cells; in 2 patients, to increased numbers of CD3+ and CD8+ and CD3+ and CD4+ T
      cells. In all responding patients, conversion to complete donor hematopoiesis
      occurred in the first 2 months after DLI. The single nonresponding patient
      remained it 100% recipient hematopoiesis. The TCR repertoire complexity was
      examined by polymerase chain reaction amplification of complementary-determining
      region 3 (CDR3) derived from 24 Vbeta gene subfamilies. In 2 patients, the
      initiation of myeloma response and conversion to complete donor hematopoiesis was
      associated with normalization of TCR complexity. Complete donor chimerism and
      normal TCR complexity remained stable in all patients and did not change with
      subsequent relapse or development of graft-versus-host disease (GVHD). Thus,
      conversion to full donor chimerism was temporally associated with the antimyeloma
      effect of DLI but not with the development of GVHD. Nevertheless, the maintenance
      of stable donor hematopoiesis did not prevent disease relapse and was not
      associated with prolonged remission. The selective relapse of myeloma cells
      without concomitant return of mixed hematopoietic chimerism suggests that myeloma
      tumor cells in some patients develop resistance to immune destruction.

PMID- 10917574
TI  - Pulmonary toxicity syndrome in breast cancer patients undergoing BCNU-containing
      high-dose chemotherapy and autologous hematopoietic cell transplantation.
AB  - We performed a retrospective review to investigate pulmonary toxicity syndrome
      (PTS) in a cohort of breast cancer patients undergoing BCNU-containing high-dose
      chemotherapy (HDC). Our aim was to characterize presentation, identify risk
      factors, determine outcome following therapy, and find any association with
      differences in survival. We reviewed the data of 152 patients with stage II or
      III or metastatic breast cancer treated with cyclophosphamide 5625 mg/m2,
      cisplatin 165 mg/m2, and BCNU 600 mg/m2 followed by autologous peripheral blood
      hematopoietic cell transplantation. During follow-up, PTS was diagnosed when the
      following criteria were met: (1) presentation with typical clinical symptoms of
      PTS, (2) an absolute carbon monoxide diffusion capacity (DLCO) decline of 10%
      compared with pre-HDC DLCO, and (3) no clinical evidence of active pulmonary
      infection. Patients were then treated with a course of corticosteroid therapy.
      The incidence of PTS for all 152 patients was 59%, with a median onset at 45 days
      (range, 21-149 days) post-HDC. The median absolute DLCO decrement was 26% (range,
      10%-73%) at diagnosis of PTS. There was no significant correlation between
      patient age, stage of breast cancer, pre-HDC chemotherapy regimen, pre-HDC chest
      wall radiotherapy, tobacco use, prior lung disease, or baseline pulmonary
      function test results and the development of PTS. We did observe an interesting
      association between PTS and the development of a noncholestatic elevation of
      transaminases. Of PTS patients treated with prednisone therapy for a median of
      105.5 days (range, 44-300 days), 91% achieved resolution of their PTS without
      pulmonary sequelae. At 3 years, the overall survival (OS) of stage II or III
      patients who developed PTS was 84% (95% confidence interval [CI], 73%-95%); of
      metastatic breast cancer patients with PTS, the OS was 58% (95% CI, 38%-78%).
      These values were not significantly different from those of patients who did not
      develop PTS (91% [95% confidence interval [CI], 81%-100%] and 53% [95% CI, 32%
      74%], respectively). No significant differences in disease-free or event-free
      survival were observed between patients with and without PTS. The incidence of
      PTS in breast cancer patients treated with a BCNU-containing HDC regimen can be
      remarkably high. Treatment with a course of corticosteroid therapy is successful
      in the vast majority.

PMID- 10917575
TI  - Introduction of human erythropoietin receptor complementary DNA by retrovirus
      mediated gene transfer into murine embryonic stem cells enhances erythropoiesis
      in developing embryoid bodies.
AB  - To evaluate the role of the erythropoietin (Epo) receptor (R) in erythropoiesis
      in more primitive stem cells, we assessed the influence of retrovirus-mediated
      gene transfer of human (h) EpoR complementary DNA (cDNA) into murine embryonic
      stem (ES) cells on erythroid differentiation of these cells. The hEpoR cDNA was
      efficiently transduced into ES cells, forming hEpoR that stably expressed ES (ES
      hEpoR) cells. Expression of hEpoR cDNA was confirmed in ES-hEpoR cells by reverse
      transcriptase-polymerase chain reaction and Northern blot analysis. Colony assays
      demonstrated that definitive erythroid and primitive erythroid colonies were
      significantly increased from ES-hEpoR cells, when compared with mock virus
      transduced ES (ES-Neo) cells, during the time course of differentiation induced
      by withdrawal of leukemia inhibitory factor, in either the presence or the
      absence of Epo. Multipotential colony-forming units (CFU-Mix) were also increased
      in ES-hEpoR cells at different stages of differentiation, but no changes were
      detected for CFU-granulocyte-macrophage colonies (CFU-GM). Time course studies by
      Northern blot analysis demonstrated elevated levels of expression of beta-H1 and
      beta-Major globin genes in embryoid bodies derived from ES-hEpoR cells stimulated
      with Epo, when compared with similar expression from ES-Neo cells. Expression of
      the GATA-1 gene was enhanced in ES-hEpoR cells, when compared with ES-Neo cells,
      beginning immediately after initiation of the cultures until 8 days of
      differentiation. These data indicate that primitive and definitive erythropoiesis
      in differentiating embryoid bodies can be enhanced by retrovirus-mediated gene
      transfer of an hEpoR gene.

PMID- 10917576
TI  - Infiltrating T cells during liver graft-versus-host disease show a restricted T
      cell repertoire.
AB  - Data from animal models have shown that hepatic graft-versus-host disease (GVHD)
      may be mediated by donor T cells interacting with liver adhesion molecules, other
      minor histocompatibility antigens, or both. We hypothesized that T-cell
      infiltrates within a liver biopsy during clinical GVHD would show a restricted T
      cell response because the T cells would be responding to a limited number of
      antigens. We studied the peripheral T-cell repertoire and the liver-infiltrating
      T-cell repertoire of a patient who developed skin GVHD and subsequent liver GVHD
      after a matched sibling bone marrow transplantation for acute myeloid leukemia.
      Spectratype analysis of peripheral blood at the time of liver GVHD revealed that
      the patient had reconstituted a complex peripheral T-cell repertoire as evidenced
      by the presence of complementarity-determining region 3 (CDR3) length
      heterogeneity in most of the T-cell families. The repertoire complexity was
      skewed in variable gene beta (VB) 5.3, VB4, VB7, VB8, and VB15. Spectratype
      analysis on the liver biopsy sample revealed a limited infiltrate with an
      oligoclonal expansion in VBs 4, 7, and 8. We evaluated the T-cell infiltrate in
      more detail by sequencing the relevant expansions noted by spectratype and
      developing probes for the predominant CDR3 sequences. These clonotype probes were
      hybridized to peripheral blood and liver samples from the patient, a T-cell line
      developed from the patient's peripheral blood at the time of the initial skin
      GVHD, the donor's blood and marrow, and control samples. The results showed that
      the T-cell infiltrate during liver GVHD is mediated by a limited number of T
      cells, and that those cells are mostly different from the ones expanded from the
      peripheral blood during an acute skin GVHD reaction. These data support the
      concept that liver GVHD is a response to tissue-specific minor histocompatibility
      antigens.

PMID- 10917577
TI  - Endovascular sclerotherapy, surgery, and surgery plus sclerotherapy in
      superficial venous incompetence: a randomized, 10-year follow-up trial--final
      results.
AB  - The study was planned to evaluate efficacy and costs of endovascular
      sclerotherapy (ES) in comparison with surgery and surgery associated with
      sclerotherapy in a prospective (10-year follow-up), good-clinical-practice study.
      Patients with varicose veins and pure, superficial venous incompetence were
      included. Of the patients randomized into the three groups 39 (group A) were
      treated with ES, 40 (B) with surgery + sclerotherapy, and 42 with surgery only
      (C). Surgery consisted of ligation of the SFJ (saphenofemoral junction) and of
      incompetent veins detected with color duplex. Of the preselected 150 patients,
      121 subjects entered the study; 96 completed the 10-year follow-up (mean age 52.6
      +/- 6 years; 51 men, 45 women). Dropouts were due to nonmedical problems. At 10
      years no incompetence was observed in subjects treated with SPJ ligation (B and
      C). In the ES group 18.8% of the SFJs were patent and incompetent and in 43.8% of
      limbs the distal (below-knee) venous system was still incompetent [16.1% in the
      surgery + sclerotherapy group (p < 0.05) and 36% in the group treated with
      surgery only (p < 0.05 vs B and 0.05 vs A)]. Color duplex of the long saphenous
      vein indicated atrophy or obstruction of a segment (average 6.7 cm) after SFJ
      ligation (4.2 cm after ES). The cost of ES was 68% of surgery while the cost of
      surgery and sclerotherapy was 122% of surgery only. Endovascular sclerotherapy is
      an effective, cheaper treatment option, but surgery after 10 years is superior.

PMID- 10917578
TI  - An open-label, randomized multicenter study comparing the efficacy and safety of
      Cyclo 3 Fort versus hydroxyethyl rutoside in chronic venous lymphatic
      insufficiency.
AB  - The present study was designed to compare the safety and efficacy of a
      combination of Ruscus aculeatus, hesperidin methyl chalcone, and ascorbic acid
      (Cyclo 3 Fort) versus that of hydroxyethyl rutoside in treatment of chronic
      venous lymphatic insufficiency. This open-label, randomized multicenter study was
      conducted on outpatients treated for 90 days. The patients were from three
      different regions of Argentina. Eighty patients, men and women, 30 to 70 years of
      age, with symptoms of chronic venous lymphatic insufficiency, ie, heavy, tired,
      swollen, or painful legs, were enrolled and assigned to two groups: one group
      treated with Cyclo 3 Fort, the other with rutoside. The symptoms were assessed at
      baseline, and after 30, 60, and 90 days. The patient was asked to assess
      subjective symptoms, and the physician measured the size of the affected limbs.
      The efficacy was rated on a 3-point scale and safety was evaluated by the number
      of side effects. The results show that when all patients were comparable at
      baseline, after 90 days, patients treated with Cyclo 3 Fort reported more rapid
      and complete regression of symptoms than those in the rutoside group, a
      statistically significant difference (p < 0.01). Likewise, a significant
      reduction in affected limb size was observed in both groups but persisted after
      90 days in the Cyclo 3 Fort group only (p < 0.01). Cyclo 3 Fort was safe and more
      effective than rutoside in the treatment of venous lymphatic insufficiency, and
      the Cyclo 3 Fort efficacy is probably associated with its unique mechanism of
      action.

PMID- 10917579
TI  - Additive effect of coexistent type 2 diabetes and arterial hypertension on
      endothelial dysfunction in resistance arteries of human forearm vasculature.
AB  - Population studies suggest that vascular complications accumulate when arterial
      hypertension supervenes on diabetes mellitus. Although it has been demonstrated
      that endothelial function is impaired in patients with either diabetes mellitus
      or arterial hypertension it is unknown whether or not both diseases exert
      additive effects on endothelial dysfunction. The authors therefore investigated
      endothelium-dependent and endothelium-independent vasodilation in the forearm
      vasculature of 44 individuals: in 10 type 2 diabetic patients (DM), in 12
      patients with arterial hypertension (HT), in 10 patients with both DM and HT
      (DM+HT), and in 12 healthy control subjects (C). Forearm blood flow (FBF) was
      measured by venous occlusion plethysmography at rest and following intraarterial
      infusion of acetylcholine (ACh) and the NO-donor sodium nitroprusside (SNP) at
      increasing doses. FBF at rest was significantly lower in diabetic patients: 2.2
      +/- 0.1 (DM) and 2.6 +/- 0.2 (DM+HT) versus 3.1 +/- 0.1 (HT) and 3.4 +/- 0.2 (C)
      mL/min per 100 mL of tissue. ACh and SNP both increased FBF dose-dependently in
      each group. The maximum response to ACh was progressively decreased in DM and HT:
      13.7 (C) > 8.1 (DM) > 7.6 (HT) > and 5.7 (DM+HT) mL/min per 100 mL of tissue.
      Reduction of the endothelium-dependent flow reserve assessed as percent increase
      in maximum FBF was also impaired following the same rank order: 349 (C) > 268
      (DM) > 160 (HT) > 126 (DM+HT)%. The flow response to the NO-donor SNP amounted
      to: 327 (C), 306 (DM), 200 (HT), and 194% (DM+HT). In DM+HT the reduction of
      endothelium-dependent flow response was more pronounced compared with the
      endothelium-independent flow response. The present data provide evidence that
      type 2 diabetes and arterial hypertension impair endothelium-dependent dilation
      of resistance arteries in an additive manner suggesting that this progressive
      endothelial dysfunction might contribute to the increased incidence of
      cardiovascular complications when both diseases are coexistent.

PMID- 10917580
TI  - Study of the value of corrected ejection fraction in the evaluation of left
      ventricular function in patients with mitral or aortic regurgitation.
AB  - Evaluation of left ventricular function in the presence of valvular regurgitation
      is still a clinical problem because ejection phase indices including ejection
      fraction are heavily dependent on preload and afterload and cannot be regarded as
      reliable indices of contractility in diseases associated with altered loading
      conditions. The authors attempted to evaluate the usefulness of the new index
      corrected ejection fraction in the evaluation of left ventricular (LV) function
      in patients with chronic mitral (MR) or aortic regurgitation (AR). The study
      included 21 patients with chronic severe MR (11 patients) and AR (10 patients)
      with a mean age of 18 years. All patients underwent valve replacement or repair.
      Echo Doppler study was performed preoperatively and postoperatively and included
      measurement of the following LV parameters: end-diastolic dimension (EDD), end
      diastolic volume (EDV), end-systolic dimension (ESD), end-systolic volume (ESV),
      ejection fraction (EF), systolic blood pressure/end-systolic dimension (SBP/ESD);
      also mitral and aortic stroke volume were calculated cross-sectional area (CSA) x
      time velocity integral TVI. Corrected ejection fraction (EFc) was derived from
      the following equation: EFc = [EF + square root of (ASV x MSV) / EDV] / 2. The
      mean preoperative EFc did not change significantly after surgical correction of
      mitral or aortic regurgitation. Preoperative EFc did not show significant
      difference compared with postoperative EF in the two groups. Preoperative EFc
      correlated significantly with other preoperative and postoperative indices of LV
      function. Postoperative EFc showed very close correlation with other
      postoperative parameters. Thus, using the new index-corrected ejection fraction
      in the assessment of LV function in patients with mitral or aortic regurgitation
      has several advantages: Noninvasive, independent of loading changes, helpful in
      predicting the immediate postoperative clinical course, and a reliable index for
      evaluation of LV systolic function preoperatively and postoperatively.

PMID- 10917581
TI  - Accumulation of lymphocytes, dendritic cells, and granulocytes in the aortic wall
      affected by Takayasu's disease.
AB  - The aim of this study was to analyze the cellular composition of the arterial
      wall in Takayasu's disease and to investigate the contribution of the various
      cell types to the immunoinflammatory processes and degenerative alterations of
      the vessel wall in this disease. Specimens of aorta were obtained at operation
      from 10 patients with Takayasu's arteritis. The duration of disease ranged from 2
      months to 13 years. Immunohistochemical investigation was carried out using the
      antibodies CD3 (to identify T-cells), CD20 (B-cells), S-100 (dendritic cells),
      CD68 (macrophages), CD15 (granulocytes), von Willebrand factor (endothelial
      cells), and alpha-smooth muscle actin (smooth muscle cells). All specimens showed
      distinctive histologic features of Takayasu's arteritis and contained
      inflammatory infiltrates, but the degree of their accumulation within the aortic
      wall varied. Inflammatory infiltrates within the deep part of the intima, around
      areas of neovascularization and within the adventitia contained T-cells
      colocalizing with dendritic cells. Nodules formed by large numbers of
      intermingling T-cells and B-cells enriched with dendritic cells were observed in
      the adventitia. Massive accumulation of granulocytes and their destruction within
      the adventitia were prominent in all cases. This is the first study that
      establishes the presence of dendritic cells and granulocytes in Takayasu's
      disease. Dendritic cells are probably involved in the immunoinflammatory
      processes through their interaction with T-cells and B-cells. The present
      observations may help understanding of the pathogenesis of Takayasu's disease.

PMID- 10917582
TI  - Transient U wave inversion during treadmill exercise testing in patients with
      left anterior descending coronary artery disease.
AB  - The transient U wave inversion during exercise is specific for detecting left
      anterior descending coronary artery (LAD) disease. In a homogeneous patient group
      restricted to LAD disease, however, the significance of the electrocardiographic
      finding has not yet been clarified. Thus, clinical characteristics in patients
      with angiographically documented one-vessel disease of the LAD and exercise
      induced U wave inversion were delineated. Symptom-limited treadmill exercise
      testing was performed in 60 patients (43 men, 17 women; mean age 64 +/- 8 years)
      with angina pectoris whose culprit lesion was located only in the LAD. U wave
      polarity and amplitude were determined before, during, and after exercise with
      the P-Q segment as the isoelectric line. Exercise-induced transient U wave
      inversion was defined as positive when there was a discrete negative deflection >
      or = 0.05 mV within the T-P segment. Of all patients, 16 (27%) had exercise
      induced U wave inversion. There were no differences in age, male gender,
      antianginal medication use, and coronary angiographic data between the two
      patients groups: patients with and without U wave inversion. Heart rate and
      double product of heart rate and systemic systolic blood pressure at peak
      exercise were also similar. Prevalence of abnormal exercise-induced S-T segment
      shift was 94% (15 of 16 patients) and 61% (27 of 44 patients) of patients with
      and without U wave inversion, respectively. The difference was statistically
      significant (p = 0.02). Among patients with exercise-induced S-T segment shift,
      the proportion of patients with S-T segment elevation to all the patients was
      larger in patients with U wave inversion than in patients without U wave
      inversion [3 (20%) of 15 patients vs 0 (0%) of 27 patients, p = 0.03)]. In
      conclusion, the exercise-induced U wave inversion in patients with one-vessel
      disease of the LAD indicates the severe degree of myocardial ischemia induced in
      the territory perfused by the LAD. However, the electrocardiographic finding does
      not appear to have independent significance since it closely correlates with the
      presence of S-T segment shift.

PMID- 10917583
TI  - Ticlopidine-induced severe agranulocytosis after the placement of coronary artery
      stent--a case report.
AB  - Ticlopidine is an oral antiplatelet agent frequently utilized in the treatment of
      cerebrovascular disease. It is rarely associated with severe bone marrow
      suppression. A case of an elderly woman is reported who developed febrile
      agranulocytosis two months after commencing ticlopidine but who had a favorable
      outcome after cessation of that drug and treatment with granulocyte colony
      stimulating factor (G-CSF). All patients should have regular monitoring of their
      blood counts during therapy with ticlopidine.

PMID- 10917584
TI  - Nonatherosclerotic aneurysm of the left circumflex coronary artery presenting
      with accelerated angina pectoris: response to medical management--a case report.
AB  - Coronary artery aneurysm is defined as coronary dilatation with a diameter of
      more than 1.5 times the adjacent normal coronary artery. Most of the coronary
      aneurysms remain asymptomatic. More than 90% of coronary aneurysms are of
      atherosclerotic origin. Nonatherosclerotic coronary aneurysms are rare, and the
      majority of them are diffuse. Among the three major coronary arteries, the left
      circumflex artery is the least commonly involved. The management strategies for
      nonatherosclerotic coronary aneurysms are not clear, and each case should be
      managed on an individual basis depending on the clinical context. Here described
      is a case of a discrete nonatherosclerotic aneurysm of the left circumflex
      coronary artery in a 46-year-old man who presented with accelerated angina
      pectoris and was treated medically. The patient was free of symptoms on 2-year
      follow-up. The clinical perspectives of the nonatherosclerotic coronary aneurysm
      are discussed.

PMID- 10917585
TI  - Giant noninflammatory and nonatherosclerotic coronary arterial aneurysm in the
      left main trunk assessed by intravascular ultrasound imaging--a case report.
AB  - A case of a giant noninflammatory and nonatherosclerotic coronary arterial
      aneurysm in the left main trunk of a 69-year-old female is reported. Preoperative
      intravascular ultrasound (IVUS) images were helpful for visualizing the
      morphologic and histologic features of the coronary aneurysm. They were also
      useful for determining the etiologic background and surgical procedure.

PMID- 10917586
TI  - Isolated dissection of the celiac artery--a case report.
AB  - Isolated arterial dissection, which occurs with the absence of aortic dissection,
      has been reported in carotid and renal arteries but rarely in visceral arteries.
      A case of isolated celiac artery dissection is reported here. A healthy 58-year
      old man experienced sudden upper abdominal pain, which continued for several
      days. A body computed tomogram (CT) showed a multiple low-density wedge-shaped
      area in the spleen, which was diagnosed as splenic infarction, and an aneurysm
      with thrombus in the celiac artery. A selective angiogram showed dilatation of
      the celiac artery with wall irregularity, and proximal occlusion of the hepatic
      artery. The distal hepatic artery was fed by collateral arteries from the
      superior mesenteric artery. Splenic infarction was probably due to the embolism
      from the thrombus in the dissected celiac artery. The absence of other vascular
      lesions and causes or risks for the arterial dissection would suggest the
      occurrence of spontaneous dissection. The dissection of visceral arteries should
      be considered in diagnosing acute abdominal pain.

PMID- 10917587
TI  - Bilateral pulmonary artery aneurysm associated with bilateral pulmonary
      thromboembolism, superior vena caval thrombosis, and Chagas' disease--a case
      report.
AB  - The authors report a case of bilateral pulmonary artery aneurysm in a patient
      with chronic Chagas' disease and compensated congestive heart failure in whom
      clinical clues suggested pulmonary thromboembolism, and the actual nature of the
      lesions was discovered at the time of conventional imaging investigations. This
      case shows the rarity of bilateral pulmonary aneurysm associated with bilateral
      pulmonary thromboembolism and the importance of an awareness of this condition in
      the differential diagnosis for lung masses.

PMID- 10917588
TI  - Regarding "Edema and leg volume: methods of assessment".

PMID- 10917589
TI  - Recognition of functional groups in an RNA helix by a class I tRNA synthetase.

PMID- 10917590
TI  - Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic MOCS1A
      and MOCS1B open reading frames.
AB  - Molybdenum is an essential cofactor in many enzymes, but must first be complexed
      by molybdopterin, whose synthesis requires four enzymatic activities. The first
      two enzymes of this pathway are encoded by the MOCS1 locus in humans. We describe
      here a remarkably well-conserved novel mRNA splicing phenomenon that produces
      both an apparently bicistronic MOCS1AM-OCS1B transcript, as well as a distinct
      class of monocistronic transcript. The latter are created by a variety of
      splicing mechanisms (alternative splice donors, alternative splice acceptors, and
      exon-skipping) to bypass the normal termination nonsense codon of MOCS1A
      resulting in fusion of the MOCS1A and MOCS1B open reading frames. Therefore,
      these "no-nonsense" transcripts encode a single bifunctional protein embodying
      both MOCS1A and MOCS1B activities. This coexpression profile was observed in
      vertebrates (human, mouse, cow, rabbit, opossum, and chicken) and invertebrates
      (fruit fly and nematode) spanning at least 700 million years of evolution. Our
      phylogenetic data also provide evidence that the bicistronic form of MOCS1 mRNA
      is likely to only produce MOCS1A protein and, combined with Northern analyses,
      suggests that MOCS1B is translated only as a fusion with MOCS1A. Taken together,
      the data presented here demonstrate a very highly conserved and physiologically
      relevant dynamic splicing scheme that profoundly influences the protein-coding
      potential of the MOCS1 locus.

PMID- 10917592
TI  - Nonsense-mediated decay mutants do not affect programmed -1 frameshifting.
AB  - Sequences in certain mRNAs program the ribosome to undergo a noncanonical
      translation event, translational frameshifting, translational hopping, or
      termination readthrough. These sequences are termed recoding sites, because they
      cause the ribosome to change temporarily its coding rules. Cis and trans-acting
      factors sensitively modulate the efficiency of recoding events. In an attempt to
      quantitate the effect of these factors we have developed a dual-reporter vector
      using the lacZ and luc genes to directly measure recoding efficiency. We were
      able to confirm the effect of several factors that modulate frameshift or
      readthrough efficiency at a variety of sites. Surprisingly, we were not able to
      confirm that the complex of factors termed the surveillance complex regulates
      translational frameshifting. This complex regulates degradation of nonsense codon
      containing mRNAs and we confirm that it also affects the efficiency of nonsense
      suppression. Our data suggest that the surveillance complex is not a general
      regulator of translational accuracy, but that its role is closely tied to the
      translational termination and initiation processes.

PMID- 10917591
TI  - Pentamidine inhibits mitochondrial intron splicing and translation in
      Saccharomyces cerevisiae.
AB  - Pentamidine inhibits in vitro splicing of nuclear group I introns from rRNA genes
      of some pathogenic fungi and is known to inhibit mitochondrial function in yeast.
      Here we report that pentamidine inhibits the self-splicing of three group I and
      two group II introns of yeast mitochondria. Comparison of yeast strains with
      different configurations of mitochondrial introns (12, 5, 4, or 0 introns)
      revealed that strains with the most introns were the most sensitive to growth
      inhibition by pentamidine on glycerol medium. Analysis of blots of RNA from yeast
      strains grown in raffinose medium in the presence or absence of pentamidine
      revealed that the splicing of seven group I and two group II introns that have
      intron reading frames was inhibited by the drug to varying extents. Three introns
      without reading frames were unaffected by the drug in vivo, and two of these were
      inhibited in vitro, implying that the drug affects splicing by acting directly on
      RNA in vitro, but on another target in vivo. Because the most sensitive introns
      in vivo are the ones whose splicing depends on a maturase encoded by the intron
      reading frames, we tested pentamidine for effects on mitochondrial translation.
      We found that the drug inhibits mitochondrial but not cytoplasmic translation in
      cells at concentrations that inhibit mitochondrial intron splicing. Therefore,
      pentamidine is a potent and specific inhibitor of mitochondrial translation, and
      this effect explains most or all of its effects on respiratory growth and on in
      vivo splicing of mitochondrial introns.

PMID- 10917593
TI  - Mature mRNAs accumulated in the nucleus are neither the molecules in transit to
      the cytoplasm nor constitute a stockpile for gene expression.
AB  - In higher eukaryotes, the regulation of pre-mRNA processing is still poorly
      known. The accumulation of various mature mRNAs, which can be observed in the
      nuclei of mammalian cells, is suggestive of a regulatory role of transport.
      However, the significance of these nuclear mRNA is presently unknown. We have
      used a tetracycline-regulated promoter to investigate the dynamics of these pools
      of mRNAs upon arrest of transcription. We observed, for beta-globin and LT-alpha
      genes, a slow disappearance of these mRNA from the nucleus, with an apparent half
      life that is similar to their cytoplasmic half-life. In view of these dynamics,
      these mRNA cannot simply be mature mRNAs in transit to the cytoplasm. They could
      be mRNAs retained in the nucleus, provided that the regulation of mRNA stability
      is comparable in the nucleus and the cytoplasm. But, because of their limited
      stability, these nuclear mRNAs cannot constitute a significant stock for gene
      expression. Alternatively, they could reflect a bidirectional transport of mRNA,
      that is, to and from the cytoplasm, which would provide a direct explanation for
      the similarity in both compartments of their half-life and poly(A) tail
      shortening over time.

PMID- 10917594
TI  - Cross-talk between orientation-dependent recognition determinants of a complex
      control RNA element, the enterovirus oriR.
AB  - The coxsackie B3 virus oriR is an element of viral RNA thought to promote the
      assembly of a ribonucleoprotein complex involved in the initiation of genome
      replication. The mutual orientation of its two helical domains X and Y is
      determined by a kissing interaction between the loops of these domains. Here, a
      genetic approach was worked out to identify spatial orientation-dependent
      recognition signals in these helices. Spatial orientation changes (due to linear
      and rotational shifts) were introduced by appropriate insertions/deletions of a
      single base pair into one or both of the domains, and phenotypic consequences
      caused by these mutations were studied. The insertion of a base pair into domain
      Y caused a defect in viral reproduction that could be suppressed by a base-pair
      insertion into domain X. Similarly, a defect in viral replication caused by a
      base-pair deletion from domain X could be suppressed by a base-pair deletion from
      domain Y. Thus, certain areas of the two domains should cross-talk to one another
      in the sense that a change of space position of one of them required an adequate
      reply (change of space position) from the other. Phenotypic effects of the local
      rotation of one or more base pairs (and of some other mutations) in either domain
      X or domain Y suggested that the two most distal base pairs of these domains
      served as orientation-dependent recognizable signals. The results were also
      consistent with the notion that the recognition of the distal base pair of domain
      Y involved a mechanism similar to the intercalation of an amino acid residue.

PMID- 10917595
TI  - Selective importation of RNA into isolated mitochondria from Leishmania
      tarentolae.
AB  - All mitochondrial tRNAs in kinetoplastid protozoa are encoded in the nucleus and
      imported from the cytosol. Incubation of two in vitro-transcribed tRNAs,
      tRNA(Ile)(UAU) and tRNA(Gln)(CUG), with isolated mitochondria from Leishmania
      tarentolae, in the absence of any added cytosolic fraction, resulted in a
      protease-sensitive, ATP-dependent importation, as measured by nuclease
      protection. Evidence that nuclease protection represents importation was obtained
      by the finding that Bacillus subtilis pre-tRNA(Asp) was protected from nuclease
      digestion and was also cleaved by an intramitochondrial RNase P-like activity to
      produce the mature tRNA. The presence of a membrane potential is not required for
      in vitro importation. A variety of small synthetic RNAs were also found to be
      efficiently imported in vitro. The data suggest that there is a structural
      requirement for importation of RNAs greater than approximately 17 nt, and that
      smaller RNAs are apparently nonspecifically imported. The signals for importation
      of folded RNAs have not been determined, but the specificity of the process was
      illustrated by the higher saturation level of importation of the mainly
      mitochondria-localized tRNA(Ile) as compared to the level of importation of the
      mainly cytosol-localized tRNA(Gln). Furthermore, exchanging the D-arm between the
      tRNA(Ile) and the tRNA(Gln) resulted in a reversal of the in vitro importation
      behavior and this could also be interpreted in terms of tertiary structure
      specificity.

PMID- 10917596
TI  - dADAR, a Drosophila double-stranded RNA-specific adenosine deaminase is highly
      developmentally regulated and is itself a target for RNA editing.
AB  - We have identified a homolog of the ADAR (adenosine deaminases that act on RNA)
      class of RNA editases from Drosophila, dADAR. The dADAR locus has been localized
      to the 2B6-7 region of the X chromosome and the complete genomic sequence
      organization is reported here. dADAR is most homologous to the mammalian RNA
      editing enzyme ADAR2, the enzyme that specifically edits the Q/R site in the pre
      mRNA encoding the glutamate receptor subunit GluR-B. Partially purified dADAR
      expressed in Pichia pastoris has robust nonspecific A-to-I deaminase activity on
      synthetic dsRNA substrates. Transcripts of the dADAR locus originate from two
      regulated promoters. In addition, alternative splicing generates at least four
      major dADAR isoforms that differ at their amino-termini as well as altering the
      spacing between their dsRNA binding motifs. dADAR is expressed in the developing
      nervous system, making it a candidate for the editase that acts on para voltage
      gated Na+ channel transcripts in the central nervous system. Surprisingly, dADAR
      itself undergoes developmentally regulated RNA editing that changes a conserved
      residue in the catalytic domain. Taken together, these findings show that both
      transcription and processing of dADAR transcripts are under strict developmental
      control and suggest that the process of RNA editing in Drosophila is dynamically
      regulated.

PMID- 10917597
TI  - Junction phosphate is derived from the precursor in the tRNA spliced by the
      archaeon Haloferax volcanii cell extract.
AB  - RNA splicing in archaea requires at least an endonuclease and a ligase, as is the
      case for the splicing of eukaryal nuclear tRNAs. Splicing endonucleases from
      archaea and eukarya are homologous, although they differ in subunit composition
      and substrate recognition properties. However, they all produce 2',3' cyclic
      phosphate and 5'-hydroxyl termini. An in vitro-transcribed, partial intron
      deleted Haloferax volcanii elongator tRNA(Met) has been used to study splicing by
      H. volcanii cell extracts. Substrates and products were analyzed by nearest
      neighbor analyses using nuclease P1 and RNase T2, and fingerprinting analyses
      using acid-urea gels in the first dimension and gradient thin layer
      chromatography in the second dimension. The results suggest that 2',3' cyclic
      phosphate at the 3' end of the 5' exon is converted into the splice junction
      phosphate forming a 3',5'-phosphodiester linkage. This resembles the animal cell
      type systems where the junction phosphate preexists in the transcript, and
      differs from yeast type systems, where GTP is the source of junction phosphate.

PMID- 10917598
TI  - Unusual synthesis by the Escherichia coli CCA-adding enzyme.
AB  - The tRNA 3' end contains the conserved CCA sequence at the 74-76 positions. The
      CCA sequence is synthesized and maintained by the CCA-adding enzymes. The
      specificity of the Escherichia coli enzyme at each of the 74-76 positions was
      investigated using synthetic minihelix substrates that contain permuted 3' ends.
      Results here indicate that the enzyme has the ability to synthesize unusual 3'
      ends. When incubated with CTP alone, the enzyme catalyzed the addition of C74,
      C75, C76, and multiple Cs. Although the addition of C74 and C75 was as expected,
      that of C76 and multiple Cs was not. In particular, the addition of C76 generated
      CCC, which would have conflicted with the biological role of the enzyme. However,
      the presence of ATP prevented the synthesis of CCC and completely switched the
      specificity to CCA. The presence of ATP also had an inhibitory effect on the
      synthesis of multiple Cs. Thus, the E. coli CCA enzyme can be a poly(C)
      polymerase but its synthesis of poly(C) is regulated by the presence of ATP.
      These features led to a model of CCA synthesis that is independent of a nucleic
      acid template. The synthesis of poly(C) by the CCA-adding enzyme is reminiscent
      of that of poly(A) by poly(A) polymerase and it provides a functional rationale
      for the close sequence relationship between these two enzymes in the family of
      nucleotidyltransferases.

PMID- 10917599
TI  - Aminoglycoside antibiotics mediate context-dependent suppression of termination
      codons in a mammalian translation system.
AB  - The translation machinery recognizes codons that enter the ribosomal A site with
      remarkable accuracy to ensure that polypeptide synthesis proceeds with a minimum
      of errors. When a termination codon enters the A site of a eukaryotic ribosome,
      it is recognized by the release factor eRF1. It has been suggested that the
      recognition of translation termination signals in these organisms is not limited
      to a simple trinucleotide codon, but is instead recognized by an extended
      tetranucleotide termination signal comprised of the stop codon and the first
      nucleotide that follows. Interestingly, pharmacological agents such as
      aminoglycoside antibiotics can reduce the efficiency of translation termination
      by a mechanism that alters this ribosomal proofreading process. This leads to the
      misincorporation of an amino acid through the pairing of a near-cognate aminoacyl
      tRNA with the stop codon. To determine whether the sequence context surrounding a
      stop codon can influence aminoglycoside-mediated suppression of translation
      termination signals, we developed a series of readthrough constructs that
      contained different tetranucleotide termination signals, as well as differences
      in the three bases upstream and downstream of the stop codon. Our results
      demonstrate that the sequences surrounding a stop codon can play an important
      role in determining its susceptibility to suppression by aminoglycosides.
      Furthermore, these distal sequences were found to influence the level of
      suppression in remarkably distinct ways. These results suggest that the mRNA
      context influences the suppression of stop codons in response to subtle
      differences in the conformation of the ribosomal decoding site that result from
      aminoglycoside binding.

PMID- 10917602
TI  - X-ray structure and reaction mechanism of bovine heart cytochrome c oxidase.

PMID- 10917600
TI  - The human coronavirus 229E superfamily 1 helicase has RNA and DNA duplex
      unwinding activities with 5'-to-3' polarity.
AB  - The human coronavirus 229E replicase gene encodes a protein, p66HEL, that
      contains a putative zinc finger structure linked to a putative superfamily (SF) 1
      helicase. A histidine-tagged form of this protein, HEL, was expressed using
      baculovirus vectors in insect cells. The purified recombinant protein had in
      vitro ATPase activity that was strongly stimulated by poly(U), poly(dT), poly(C),
      and poly(dA), but not by poly(G). The recombinant protein also had both RNA and
      DNA duplex-unwinding activities with 5'-to-3' polarity. The DNA helicase activity
      of the enzyme preferentially unwound 5'-oligopyrimidine-tailed, partial-duplex
      substrates and required a tail length of at least 10 nucleotides for effective
      unwinding. The combined data suggest that the coronaviral SF1 helicase
      functionally differs from the previously characterized RNA virus SF2 helicases.

PMID- 10917603
TI  - Small GTPases and cell cycle regulation.

PMID- 10917601
TI  - Genetic interference in Trypanosoma brucei by heritable and inducible double
      stranded RNA.
AB  - The use of double-stranded RNA (dsRNA) to disrupt gene expression has become a
      powerful method of achieving RNA interference (RNAi) in a wide variety of
      organisms. However, in Trypanosoma brucei this tool is restricted to transient
      interference, because the dsRNA is not stably maintained and its effects are
      diminished and eventually lost during cellular division. Here, we show that
      genetic interference by dsRNA can be achieved in a heritable and inducible
      fashion. To show this, we established stable cell lines expressing dsRNA in the
      form of stem-loop structures under the control of a tetracycline-inducible
      promoter. Targeting a-tubulin and actin mRNA resulted in potent and specific mRNA
      degradation as previously observed in transient interference. Surprisingly, 10
      fold down regulation of actin mRNA was not fatal to trypanosomes. This type of
      approach could be applied to study RNAi in other organisms that are difficult to
      microinject or electroporate. Furthermore, to quickly probe the consequences of
      RNAi for a given gene we established a highly efficient in vivo T7 RNA polymerase
      system for expression of dsRNA. Using the alpha-tubulin test system we obtained
      greater than 98% transfection efficiency and the RNAi response lasted at least
      two to three cell generations. These new developments make it possible to
      initiate the molecular dissection of RNAi both biochemically and genetically.

PMID- 10917604
TI  - Phospholipase-induced modulation of rat liver mixed-function oxidase activity.

PMID- 10917605
TI  - Adaptive responses to fatty acids are mediated by the regulated expression of
      cytochromes P450.

PMID- 10917606
TI  - Lipid regulation of gene expression.

PMID- 10917607
TI  - Sphingomyelin hydrolysis and regulation of the expression of the gene for
      cytochrome P450.

PMID- 10917608
TI  - The cytochrome P450 3A4 inducer metyrapone is an activator of the human pregnane
      X receptor.

PMID- 10917609
TI  - Identification of intracellular ceramide target proteins by affinity
      chromatography and TID-ceramide photoaffinity labelling.

PMID- 10917610
TI  - Ceramide and apoptosis.

PMID- 10917611
TI  - Extracellular actions of sphingosine I-phosphate through endothelial
      differentiation gene products in mammalian cells: role in regulating
      proliferation and apoptosis.

PMID- 10917612
TI  - Recent advances in the biochemistry of glycosphingolipid metabolism.

PMID- 10917613
TI  - Gangliosides and growth factor receptor regulation.

PMID- 10917614
TI  - Membrane flow, lipid sorting and cell polarity in HepG2 cells: role of a
      subapical compartment.

PMID- 10917615
TI  - Mechanisms by which short-chain ceramides cause apoptosis.

PMID- 10917616
TI  - Regulation of sphingolipid and glycosphingolipid metabolism during neuronal
      growth and development.

PMID- 10917618
TI  - Gene structure of apolipoprotein(a) and the regulation of its expression.

PMID- 10917617
TI  - Lipoprotein(a): the really bad cholesterol?

PMID- 10917619
TI  - Role of N-linked glycans, chaperone interactions and proteasomes in the
      intracellular targeting of apolipoprotein(a).

PMID- 10917620
TI  - Use of the West of Scotland Coronary Prevention Study bio-bank to provide new
      insights into the control of plasma lipoprotein(a) concentrations.

PMID- 10917621
TI  - Genetic polymorphisms of the gene for apolipoprotein(a) and their association
      with lipoprotein(a) levels and myocardial infarction.

PMID- 10917622
TI  - Pharmacological modification of lipoprotein(a).

PMID- 10917623
TI  - Bacterium-host protein-carbohydrate interactions and pathogenicity.

PMID- 10917624
TI  - Molecular basis of mucin-Pseudomonas interactions.

PMID- 10917625
TI  - Malaria during pregnancy: parasites, antibodies and chondroitin sulphate A.
AB  - CSA-binding forms of P. falciparum appear uncommonly in non-pregnant hosts but
      are selected by the human placenta for growth. Parasites are presumably selected
      by adherence to CSA within the vascular compartment of the placenta, allowing
      IRBCs to sequester and multiply to high density. Chondroitin sulphate appears on
      the surface of placental syncytiotrophoblasts, and CSA is a component of PGs
      found in the placenta [42], but the identification of the CSA-containing PG(s)
      mediating IRBC adhesion in vivo requires further study. Anti-adhesion antibodies
      against CSA-binding parasites are associated with protection from maternal
      malaria, but these antibodies develop only over successive pregnancies,
      accounting for the susceptibility of primigravidas to infection. PfCSA-L, the
      parasite ligand mediating adhesion to CSA, has not yet been identified but is
      known to be antigenically conserved among isolates from around the world. An anti
      adhesion vaccine delivered to women before first pregnancy could confer
      protection from maternal malaria and might be globally effective.

PMID- 10917626
TI  - Heparan sulphate and RNA-binding motifs in the malaria circumsporozoite protein.

PMID- 10917627
TI  - Role of glycans in Plasmodium falciparum infection.

PMID- 10917628
TI  - Haemophilus influenzae lipopolysaccharide.

PMID- 10917629
TI  - Glycans in meningococcal pathogenesis.

PMID- 10917630
TI  - Biosynthesis of the Escherichia coli K5 capsular polysaccharide.

PMID- 10917631
TI  - Candida cell wall mannosylation: importance in host-fungus interaction and
      potential as a target for the development of antifungal drugs.

PMID- 10917632
TI  - Biological role of Trypanosoma cruzi trans-sialidase.

PMID- 10917633
TI  - Proteophosphoglycans from Leishmania promastigotes and amastigotes.

PMID- 10917634
TI  - Synaptic targeting and regulation of GABA(A) receptors.

PMID- 10917635
TI  - GABA(B) receptors function as heterodimers.
AB  - Our current understanding is that functional GABA(B) receptors exist as
      heterodimers of two related seven-transmembrane proteins, GABA(B)-R1 and GABA(B)
      R2. GABA(B)-R1 requires GABA(B)-R2 to be expressed at the cell surface as a
      mature glycoprotein. Cloning of the GABA(B) receptor has failed to provide
      molecular evidence to support the existence of true receptor subtypes. The
      discovery of the heterodimeric nature of the GABA(B) receptor has already changed
      the way we think about GPCR function and it is likely that future studies will
      change our understanding about how receptor subtypes can be formed.

PMID- 10917636
TI  - The N-terminus of RAMPs is a critical determinant of the glycosylation state and
      ligand binding of calcitonin receptor-like receptor.

PMID- 10917637
TI  - The molecular architecture of neuronal kinase/phosphatase signalling complexes.

PMID- 10917639
TI  - Difference gel electrophoresis.

PMID- 10917638
TI  - Control of protein phosphatase I in the dendrite.

PMID- 10917640
TI  - A strategy for the characterization of protein interaction networks by mass
      spectrometry.

PMID- 10917641
TI  - Proteomics in pharmaceutical research and development.

PMID- 10917642
TI  - Generic features of quinone-binding sites.

PMID- 10917643
TI  - Structures of quinone-binding sites in bc complexes: functional implications.

PMID- 10917644
TI  - Probing the ubihydroquinone primary energy conversion site in the Rhodobacter
      capsulatus cytochrome bc1 complex.

PMID- 10917645
TI  - Famoxadone and oxazolidinones: potent inhibitors of cytochrome bc1.

PMID- 10917646
TI  - Models for structure and function in quinone-binding sites: the Escherichia coli
      quinol oxidase, cytochrome bo3.

PMID- 10917648
TI  - Quinone-binding sites in membrane proteins: what can we learn from the
      Rhodopseudomonas viridis reaction centre?

PMID- 10917647
TI  - EPR studies of the possible binding sites of the cluster N2, semiquinones, and
      specific inhibitors of the NADH:quinone oxidoreductase (complex I).

PMID- 10917649
TI  - Properties of the common inhibitor-binding domain in mitochondrial NADH
      dehydrogenase (complex I).

PMID- 10917650
TI  - Biochemical aspects of N-heterocyclic complex-I inhibitors with insecticidal
      activity.

PMID- 10917651
TI  - Ubiquinone and inhibitor sites in complex I: one, two or three?

PMID- 10917652
TI  - Structure and mechanism of cytosolic quinone reductases.

PMID- 10917653
TI  - Structural basis for high-affinity phosphoinositide binding by pleckstrin
      homology domains.

PMID- 10917654
TI  - Phosphoinositide 3-kinase knockout mice: role of p85alpha in B cell development
      and proliferation.

PMID- 10917655
TI  - Phosphoinositide 3-kinase signalling: no lipids.

PMID- 10917656
TI  - Cellular expression and function of phospholipase D1.

PMID- 10917657
TI  - ADP-ribosylation factor regulates spectrin skeleton assembly on the Golgi complex
      by stimulating phosphatidylinositol 4,5-bisphosphate synthesis.

PMID- 10917658
TI  - ADP-ribosylation factor GTPases in signal transduction and membrane traffic:
      independent functions?

PMID- 10917659
TI  - Generation of phosphatidylinositol-specific antibodies and their
      characterization.

PMID- 10917660
TI  - Phospholipase C-delta and related molecules.

PMID- 10917661
TI  - The type II PIPkins (PtdIns5P 4-kinases): enzymes in search of a function?

PMID- 10917662
TI  - Regulation of early-endosome dynamics by phosphatidylinositol 3-phosphate binding
      proteins.

PMID- 10917663
TI  - Regulation of endocytic membrane traffic by phosphatidylinositol 3-phosphate.

PMID- 10917664
TI  - Lipid kinases and trans-Golgi network membrane dynamics.

PMID- 10917665
TI  - Phosphatidylinositol 3,5-bisphosphate: a novel lipid that links stress responses
      to membrane trafficking events.

PMID- 10917666
TI  - Divergent signalling mechanisms involved in insulin-stimulated GLUT4 vesicle
      trafficking to the plasma membrane.

PMID- 10917667
TI  - Potential regulation of ADP-ribosylation factor 6 signalling by
      phosphatidylinositol 3,4,5-trisphosphate.
AB  - In this review we have described data supporting the conclusion that
      PtdIns(3,4,5)P3 may regulate the activation state of ARF6 through an ability to
      recruit the ARF exchange factors ARNO, GRP1 and cytohesin-1 to the plasma
      membrane. The downstream consequences of such a PtdIns(3,4,5)P3-dependent
      activation of ARF6 are presently unclear. However, given the role of ARF6 in
      fusion events at the plasma membrane, we have proposed that PtdIns(3,4,5)P3 may
      regulate vesicle trafficking at this membrane through its ability to activate
      ARF6. This is an attractive possibility given the number of PtdIns(3,4,5)P3
      dependent pathways which involve some aspect of vesicle trafficking at the plasma
      membrane, for instance glucose transport, membrane ruffling and cell movement.

PMID- 10917668
TI  - The assembly of the EcoKI type I DNA restriction/modification enzyme and its
      interaction with DNA.

PMID- 10917669
TI  - Restriction endonuclease reactions requiring two recognition sites.

PMID- 10917670
TI  - Using NMR as a probe of protein structure and function.

PMID- 10917671
TI  - The insulin receptor: from protein sequence to structure.
AB  - Sequences of the insulin receptor (IR), the type-I insulin-like growth-factor
      receptor (IGFR) and the insulin-receptor-related receptor show that they belong
      to a homologous family but, until recently, have given few clues about their
      structures. Three repeats of fibronectin type III have been identified close to
      the membrane. Although the N-terminal L1, Cys-rich and L2 domains of the IGFR
      have been identified from their sequences and their structures determined by X
      ray crystallography, little is known of their relative positions in the complete
      receptor in vivo. Here, we ask what can be learnt further from the analysis of
      sequences, about the structure, organization and function of the extracellular
      regions of the IR family.

PMID- 10917672
TI  - Peptide synthesis with modified trypsin.

PMID- 10917673
TI  - Generation of non-bitter casein hydrolysates by using combinations of a
      proteinase and aminopeptidases.

PMID- 10917674
TI  - Role of matrix metalloproteinases in normal and disease processes.

PMID- 10917675
TI  - The cathepsin L-like proteinases of liver fluke and blood fluke parasites of the
      trematode genera Fasciola and Schistosoma.

PMID- 10917676
TI  - The expanding superfamily of serpins: searching for the real targets.
AB  - The serpin superfamily of proteins has expanded rapidly in recent years as
      represented by the ovalbumin-type serpin subfamily. PCR methods have been used to
      identify new ovalbumin-type serpins, including leupin or SCCA-2, a close relative
      of SCCA. Although in vitro inhibition of proteases by these serpins has been
      shown, and we have evidence that leupin can protect cells against apoptosis, the
      exact role of these serpins is not well understood. Finding relevant targets is a
      major challenge in serpin biology, and we have investigated the yeast-2-hybrid
      trap for identification of new interactions. Preliminary studies suggest that
      serpins are at the upper limit for bait size, but this technique may be useful
      for identifying interactions where full-length serpin protein is not required.

PMID- 10917677
TI  - Evolution of the display technologies.

PMID- 10917678
TI  - The impact of molecular biology on crop production and crop protection.

PMID- 10917679
TI  - Screen idols: faster, smaller, cheaper and smarter.

PMID- 10917680
TI  - Lifelong learning.

PMID- 10917681
TI  - Severe penetrating injury due to a burst compact disc in a child.

PMID- 10917682
TI  - Ultrasound guided cryotherapy for retinal tears in patients with opaque ocular
      media.

PMID- 10917683
TI  - Corneal ectasia after trabeculectomy with mitomycin C application.

PMID- 10917684
TI  - Severe proliferative diabetic retinopathy associated with acromegaly.

PMID- 10917686
TI  - Unilateral ptosis due to isolated involvement of the levator muscle in acute
      orbital myositis.

PMID- 10917685
TI  - Emergency contraception and retinal vein thrombosis.

PMID- 10917687
TI  - Immunological investigations following an adverse reaction to oxybuprocaine eye
      drops.

PMID- 10917688
TI  - Utility of Fungiflora Y stain in rapid diagnosis of Acanthamoeba keratitis.

PMID- 10917689
TI  - Ophthalmic medical assistants.

PMID- 10917690
TI  - Ophthalmic medical assistants.

PMID- 10917691
TI  - Ophthalmic medical assistants.

PMID- 10917692
TI  - Aging, mitochondria, and coenzyme Q(10): the neglected relationship.

PMID- 10917693
TI  - [Role of new fluoroquinolones in respiratory infections in primary care].

PMID- 10917694
TI  - Viscosity and elasticity during collagen assembly in vitro: relevance to matrix
      driven translocation.
AB  - In order to better understand the gelation process associated with collagen
      assembly, and the mechanism of the in vitro morphogenetic phenomenon of "matrix
      driven translocation" [S.A. Newman et al. (1985) Science, 228, 885-889], the
      viscosity and elastic modulus of assembling collagen matrices in the presence and
      absence of polystyrene latex beads was investigated. Viscosity measurements at
      very low shear rates (0.016-0.0549 s(-1)) were performed over a range of
      temperatures (6.9-11.5 degrees C) in a Couette viscometer. A magnetic levitation
      sphere rheometer was used to measure the shear elastic modulus of the assembling
      matrices during the late phase of the gelation process. Gelation was detected by
      the rapid increase in viscosity that occurred after a lag time tL that varied
      between O and approximately 500 s. After a rise in viscosity that occurred over
      an additional approximately 500 s, the collagen matrix was characterized by an
      elastic modulus of the order of several Pa. The lag time of the assembly process
      was relatively insensitive to differences in shear rate within the variability of
      the sample preparation, but was inversely proportional to the time the sample
      spent on ice before being raised to the test temperature, for test temperatures >
      9 degrees C. This suggests that structures important for fibrillogenesis are
      capable of forming at 0 degrees C. The time dependence of the gelation process is
      well-described by an exponential law with a rate constant K approximately 0.1 s(
      1). Significantly, K was consistently larger in collagen preparations that
      contained cell-sized polystyrene beads. From these results, along with prior
      information on effective surface tension differences of bead-containing and bead
      lacking collagen matrices, we conclude that changes in matrix organization
      contributing to matrix-driven translocation are initiated during the lag phase of
      fibrillogenesis when the viscosity is < or = 0.1 Poise. The phenomenon may make
      use of small differentials in viscosity and/or elasticity, resulting from the
      interaction of the beads with the assembling matrix. These properties are well
      described by standard models of concentrated solutions.

PMID- 10917695
TI  - Micropuncture study of renal potassium excretion in the rat. 1964.

PMID- 10917696
TI  - Immunoglobulins in inflammation. Consensus-assisted protocol development and
      discussion forum of a study protocol on adjuvant treatment of mediastinitis with
      immunoglobulins (pentaglobulin) after cardiac surgery (ATMI).

PMID- 10917697
TI  - Commentary: Time for improved diagnosis and management of patients presenting
      with acute chest pain.

PMID- 10917698
TI  - Reforms to the health sector must retain vertical programmes like those for
      tuberculosis.

PMID- 10917699
TI  - Misconceptions about tuberculosis among immigrants to the United States.

PMID- 10917700
TI  - GMS's advice in Serious Communicable Diseases. Is consent to testing necessary
      for tuberculosis in the same way as for HIV infection?

PMID- 10917701
TI  - Tracker trials. Introduction of resistance testing might be an inappropriate use
      of resources.

PMID- 10917702
TI  - Are generalists still needed in a specialised world? General practice enables
      doctors to maintain general medical skills.

PMID- 10917703
TI  - Are generalists still needed in a specialised world? Role of accident and
      emergency doctors should be expanded.

PMID- 10917704
TI  - Tracker trials. Continuous process of trial and review is needed.

PMID- 10917705
TI  - Are generalists still needed in a specialised world? Additional issues need to be
      addressed.

PMID- 10917706
TI  - Are generalists still needed in a specialised world? Needs of patients should be
      considered.

PMID- 10917708
TI  - Qualitative research in health care. Antirealism is an excuse for sloppy work.

PMID- 10917707
TI  - Qualitative research in health care. Good communication is essential part of
      educational process.

PMID- 10917709
TI  - Open access follow up for inflammatory bowel disease. Ability of any method of
      follow up to detect cancer must be stated.

PMID- 10917710
TI  - Open access follow up for inflammatory bowel disease. Would have been better to
      use t test than Mann-Whitney U test.

PMID- 10917711
TI  - Burns after photodynamic therapy. Drug point gives misleading impression of
      incidence of burns with temoporfin (Foscan)

PMID- 10917712
TI  - Cerebral symptoms from mobile telephones.

PMID- 10917713
TI  - PBN as a possible bladder carcinogen.

PMID- 10917714
TI  - Childhood cancer and possible exposure to benzene from traffic and petrol
      stations.

PMID- 10917715
TI  - Prevalence and risk factors for latex allergy.

PMID- 10917716
TI  - Prevalence and risk factors for latex allergy: a cross sectional study in a
      United Kingdom hospital.

PMID- 10917717
TI  - The Family Risk Score for coronary heart disease: associations with lipids,
      lipoproteins, and body habitus in a middle-aged bi-racial cohort: The ARIC study.
AB  - PURPOSE: To examine the association between the Family Risk Score (FRS) for
      coronary heart disease (CHD) and body mass index (BMI), waist-to-hip ratio (WHR),
      high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol,
      triglycerides, and lipoprotein(a) protein [Lp(a)]. METHODS: FRS was computed from
      observed and expected CHD events using family data collected from 11467 black and
      white adults of the Atherosclerosis Risk in Communities Study (ARIC). BMI, WHR,
      and lipids adjusted for study center, race, education, BMI (except BMI), WHR
      (except for BMI and WHR), cigarette smoking, alcohol, and Keys' score were
      compared among low (FRS < -0.5), average (-0.5 to 0.5), and high (> 0.5) FRS
      using analysis of covariance. The association between FRS and these risk factors
      was compared to that for simpler estimates of family risk. RESULTS: Adjusted
      means of BMI, WHR, LDL, LP(a), and triglycerides were positively associated with
      FRS, whereas HDL cholesterol was inversely associated with FRS. Of demographic
      and behavioral factors, cigarette smoking was most strongly associated with FRS.
      Based on additional comparisons of adjusted means, high vs. low levels of FRS
      appear to correlate better with CHD risk factors than do the simpler family
      history assessments. CONCLUSIONS: In situations were genetic or clinical
      information is not available, FRS may be a favorable measure of familial burden
      for CHD.

PMID- 10917718
TI  - Atypical adenomatous hyperplasia of the lung problems in operative management.

PMID- 10917719
TI  - Comment on Rosell et al., Roth et al. and Gandara et al., Lung Cancer.

PMID- 10917720
TI  - Individualised pulse oximetry limits in neonatal intensive care.

PMID- 10917721
TI  - Apnoea following immunisation in premature infants.

PMID- 10917722
TI  - Randomised controlled trial of cisapride in preterm infants.

PMID- 10917723
TI  - The use of cisapride in neonates.

PMID- 10917724
TI  - Mechanism of blood pressure increase induced by dopamine in hypotensive preterm
      neonates.

PMID- 10917725
TI  - Perinatal cortical infarction with no obvious cause.

PMID- 10917726
TI  - Premedication for neonatal intubation: current practice in Australia and the
      United Kingdom.

PMID- 10917727
TI  - Retained umbilical artery catheter presenting as an umbilical abscess.

PMID- 10917728
TI  - Neonatal pain relief.

PMID- 10917729
TI  - Beat to beat left ventricular performance in spontaneous atrial fibrillation does
      not depend on afterload.

PMID- 10917730
TI  - Conference report. International Society for Interferon and Cytokine Research.

PMID- 10917731
TI  - Experiment reveals deficits in European regulation.

PMID- 10917732
TI  - Timing of surgery for patients with valvular heart disease.

PMID- 10917733
TI  - What is saw palmetto used for, and does it interact with any medications?

PMID- 10917734
TI  - Water and sodium balance: a nutritional goal.

PMID- 10917735
TI  - Forgotten twins.

PMID- 10917736
TI  - In situ monitoring of caspase activation in hepatobiliary diseases.

PMID- 10917737
TI  - p53 is involved in the differentiation but not in the differentiation-associated
      apoptosis of myoblasts.

PMID- 10917738
TI  - Genes with homology to mammalian apoptosis regulators identified in zebrafish.

PMID- 10917739
TI  - Stability of rifampicin in dissolution medium.

PMID- 10917740
TI  - In vivo comparison between computed tomography and magnetic resonance image
      analysis of the distal radius in the assessment of osteoporosis.
AB  - In a prospective case-control cross-sectional study, we investigated the
      usefulness of both computed tomography (CT) and magnetic resonance (MR) image
      analysis of the distal radius for distinguishing a small sample of fractured
      osteoporotic women from control women regardless of bone mineral density. The
      study population included 12 subjects who were divided into two groups according
      to their bone status. The first group consisted of six women with at least one
      vertebral fracture occurring in the absence of high-energy trauma, and the second
      group consisted of six women without disease affecting bone mass or bone
      metabolism. Cross-sectional and coronal slices were obtained from both CT and MR
      systems. For CT images, the slice thickness was 1000 jim and the plane resolution
      was approx 200 jim x 200 jim. MR images were obtained from a 1.5-T imager with a
      two-dimensional spin-echo Ti-weighted sequence leading to a slice thickness of
      2000 jim and a plane resolution of 195 jim x 195 jim. Bone texture analysis was
      performed using fractal and structural methods leading to the measurement of 23
      features. Most of the structural variables derived from histomorphometric
      parameters and were measured after segmentation from a binary or a skeletonized
      image. Bone densitometry was measured by dual-energy X-ray absorptiometry both at
      the lumbar spine and the nondominant femoral neck. On cross-sectional slices, 12
      variables, mainly obtained from structural analysis, were significantly different
      between the two groups for CT images (p < 0.05) against two variables only for MR
      images (p < 0.05). The number of variables statistically different between the
      two groups was significantly higher for CT images compared with MR images (p =
      0.003). In the same way, odds ratios for fracture per 1 control group standard
      deviation decrease were significant for 10 variables on CT images, whereas, in
      contrast, none of the variables measured on MRI images led to significant odds
      ratios. The results obtained for the two methods on coronal slices were poorer
      without a difference between either CT or MR images in terms of discrimination
      between fracture and nonfracture subjects. In conclusion, this study suggests
      that bone texture analysis obtained from CT compared with MRI offers a best
      discrimination between controls and osteoporotic patients, probably the result to
      the spatial resolution. which is better for CT than for MR images.

PMID- 10917741
TI  - Validation and application of dual-energy X-ray absorptiometry to measure bone
      mineral density in rabbit vertebrae.
AB  - The rabbit could be a superior animal model to use in bone physiology studies,
      for the rabbit does attain true skeletal maturity. However, there are neither
      normative bone mineral density (BMD) data on the rabbit nor are there any
      validation studies on the use of dual-energy X-ray absorptiometry (DXA) to
      measure spinal BMD in the rabbit. Therefore, our aim was twofold: first, to
      investigate whether DXA could be used precisely and accurately to determine the
      bone mineral content (BMC). bone area (BA). and BMD of the rabbit lumbar spine:
      Second. to evaluate the new generation fan-beam DXA (Hologic QDR-4500) with small
      animal software by comparing two DXA methodologies QDR-1000 and QDR-4500 with
      each other, as well as against volumetric bone density (VBMD) derived from
      Archimedes principle. As expected. there was a magnification error in the QDR
      4500 (BMC, BA. and BMD increased by 52%. 38%. and 10%, respectively, when the
      vertebrae were positioned flat against the scanning table). With the
      magnification error kept constant (vertebrae positioned 10 cm above the scanning
      table to match the height in vivo). there were no differences among the mean BMC.
      BA. and BMD of the rabbit vertebrae (Ll-L7) in vivo and in vitro using the QDR
      4500 (p > 0.05). BMC, BA, and BMD differed between QDR-1000 and QDR-4500 in vitro
      because of a magnification error when the vertebrae were flat on the table (p
      <0.0001). and, consequently. the machines did not correlate with one another (p >
      0.05). However, the BMC, BA, and BMD of the two DXAs did significantly correlate
      with each other in vivo and in vitro when the magnification error was compensated
      for (r = 0.44 and 0.52. i2 = 0.45 and 0.63. and 12 = 0.41 and 0.60. respectively.
      p < 0.05-0.008). The BMC and BMD (in vivo and in vitro) of the rabbit vertebrae
      measured by QDR-4500 was significantly correlated with VMBD, ash weight, and
      mineral content (,2 = 0.67-0.90,j <0.01-0.0001). Therefore, the QDR-4500 can be
      used to yield precise and accurate measurements of the rabbit spine.

PMID- 10917742
TI  - Novel variant of the CCR5 gene in a Vietnamese population.

PMID- 10917743
TI  - "Historical Vignettes".

PMID- 10917744
TI  - [Questions of medical studies and of advanced training in internal medicine].

PMID- 10917746
TI  - The importance of clinical leadership when it comes to cost accounting and
      planning fertility services.

PMID- 10917745
TI  - Subclavian deep vein thrombosis associated with the use of recombinant follicle
      stimulating hormone (Gonal-F) complicating mild ovarian hyperstimulation
      syndrome.
AB  - OBJECTIVE: To describe two cases of subclavian deep vein thrombosis (DVT)
      associated with the use of recombinant gonadotropins and mild ovarian
      hyperstimulation syndrome (OHSS) and review the literature associated with this
      condition. DESIGN: Retrospective study (case report). SETTING: Tertiary academic
      IVF program. PATIENT(S): Two women undergoing IVF with intracytoplasmic sperm
      injection due to male factor infertility. INTERVENTION(S): Ovaluation induction
      with recombinant FSH, IVF, and therapeutic heparinization. MAIN OUTCOME
      MEASURE(S): Coagulation studies, resolution of DVT, delivery at term. RESULT(S):
      Mild OHSS with left subclavian thrombosis occurred in two patients. Laboratory
      evaluation revealed normal protein C, protein S, antinuclear antibodies (ANA),
      and absence of antiphospholipid (APA) and anticardiolipin antibodies (ACA).
      Antithrombin III levels and coagulation studies were also within normal limits.
      Both patients tested negative for a factor V Leiden mutation and delivered
      healthy infants at term. CONCLUSION(S): Arm swelling associated with the use of
      gonadotropins during controlled ovarian hyperstimulation should be promptly
      evaluated and treated. Subclavian vein thrombosis is a rare complication of
      ovulation induction, and the possibility that recombinant gonadotropins increase
      the risk for this complication should be further studied.

PMID- 10917747
TI  - Green fluorescent protein (GFP) as gene expression reporter and vital marker for
      studying development and microbe-plant interaction in the tobacco pathogen
      Phythphthora parasitica var. nicotianae.
AB  - PEG-mediated transformation of protoplasts in the presence of lipofectin was
      achieved in Phytophthora parasitica var. nicotianae, an oomycete pathogen of
      tobacco. Using oomycete promoter and terminator sequences, a plant-adapted green
      fluorescent protein (GFP) was introduced into the microorganism. The data show
      for the first time that this eukaryotic gene reporter can be used in an oomycete,
      both as a quantitative reporter of gene induction and as a vital marker allowing
      the study of development of Phytophthora in vitro and in the host plant.

PMID- 10917748
TI  - Differential expression of cyclooxygenase 2 in human colorectal cancer.

PMID- 10917749
TI  - Proton pump inhibitors for Barrett's oesophagus.

PMID- 10917750
TI  - MCP-3 in inflammatory bowel disease.

PMID- 10917751
TI  - One minute unbuffered urease test: should it be read at 10 minutes?

PMID- 10917752
TI  - Thalidomide treatment of oesophageal ulceration.

PMID- 10917753
TI  - Use of Doppler ultrasound in Crohn's disease.

PMID- 10917754
TI  - Percutaneous drainage of echinococcal cysts (PAIR--puncture, aspiration,
      injection, reaspiration): results of a worldwide survey for assessment of its
      safety and efficacy. WHO-Informal Working Group on Echinococcosis-Pair Network.

PMID- 10917755
TI  - [Polymorphism of mono-base gene of factor XII in 5'-non-translational region
      regulating the blood concentration].

PMID- 10917756
TI  - [Discovery of new frizzled gene of human esophageal neoplasms regulating APC/beta
      catenin signaling].

PMID- 10917757
TI  - [Abnormal gap junctional communication and connexin 43 phosphorylation of
      vascular smooth muscle cultured in hyperglycemic solution].

PMID- 10917758
TI  - [Hormone replacement therapy for menopausal women].

PMID- 10917759
TI  - [Problems and therapy of acute lymphoblastic leukemia in children].

PMID- 10917760
TI  - As compared to Paracetamol, does the Paracetamol and Methionine combinations have
      better efficacy and safety and can it be used safely in the management of pyrexia
      associated with liver diseases?

PMID- 10917761
TI  - The HLA system and coronary artery disease in the Japanese population.

PMID- 10917762
TI  - Myocardial infarction and sub-acute ventricular rupture: successful outcome in
      two cases.

PMID- 10917763
TI  - An open discussion about endothelial dysfunction: is it timely to propose a
      classification?

PMID- 10917764
TI  - Congenital left ventricular diverticula.

PMID- 10917765
TI  - Management of electrical storm--is long term antiarrhythmic therapy indicated?

PMID- 10917766
TI  - Pharmaceutical price regulation in the UK.

PMID- 10917773
TI  - Biomechanical modeling of intra-abdominal pressure generation should include the
      transversus abdominis.

PMID- 10917774
TI  - No evidence of active infection with human herpesvirus 6 (HHV-6) or HHV-8 in
      chronic fatigue syndrome.

PMID- 10917775
TI  - No correlation in Epstein-Barr virus reactivation between serological parameters
      and viral load.

PMID- 10917776
TI  - Contribution of combined detection assays of p24 antigen and anti-human
      immunodeficiency virus (HIV) antibodies in diagnosis of primary HIV infection by
      routine testing.

PMID- 10917777
TI  - Determination of MIC quality control ranges for ABT-733, a novel ketolide
      antimicrobial agent. Quality Control Study Group.

PMID- 10917778
TI  - Janforum: your views and letters.

PMID- 10917779
TI  - Enterobacter cloacae outbreak in the NICU related to disinfected thermometers.
AB  - In the first week ot December 1997, an increasing incidence of neonates colonized
      with multi-drug resistant Enterobacter cloacae (MR-E. cloacae) was observed in
      the neonatal Intensive care unit of our 950-bed university hospital. Initially,
      re-enforcement of infection control practices including hand disinfection and
      cohort isolation seemed to be sufficient to control the outbreak. Nevertheless,
      an increasing number of newly admitted patients was paralleled by another rise in
      the incidence of colonized neonates. Since E. cloacae was initially found in
      urine specimens of the patients, surveillance and environmental cultures were
      aimed at procedures and instruments that might colonize the gastro-intestinal
      and/or urinary tract. E, cloacae was isolated from a single cap of an electronic
      digital thermometer. Despite banning of this possible source, newly admitted
      neonates still became colonized. The unit was closed for further admissions and a
      second round of extensive screening was started; this time including all
      available thermometers and continuous rectal temperature probes. Ready-to-use
      'disinfected thermometers and probes were found to be colonized with MR-E.
      cloacae. Observation of disinfection procedures and a laboratory investigation
      revealed that 'rushed disinfection with alcohol 80% led to a 1 in 10 chance of
      thermometers still being contaminated. Furthermore, alcoholic hand rub used for
      convenience disinfection failed to disinfect thermometers in 40% and 20% of the
      cases when done in a 'rushed' or 'careful' fashion, respectively. Adequate
      disinfection of the thermometers led to the control of the outbreak, with no new
      occurrence of MR-E. cloacae in the following months.

PMID- 10917780
TI  - Nosocomial fungaemia: a 2-year prospective study.
AB  - Eighty-six consecutive patients with fungaemia were studied during a period of 2
      years, 81% had two or more positive blood cultures. Gastrointestinal tract (28%)
      and haematological diseases (17%) were the most common underlying conditions. The
      majority of cases had received vancomycin and/or imipenem (87%) and a central
      venous catheter (78%). Candida albicans (50%) and Candida parapsilosis (17%) were
      the most frequent isolates. Overall mortality was 41%, and for patients with
      Candida tropicalis was 71%. There was not significant difference in survival with
      gender, age and days of treatment with antifungal drugs. Haematological diseases,
      neutropenia and a higher number of positive blood cultures were associated with
      poor outcome.

PMID- 10917781
TI  - The placement of MRSA carriers in private nursing homes: does information
      influence acceptance?

PMID- 10917782
TI  - Workload may be related to the spread of MRSA and other infections.

PMID- 10917783
TI  - 7th European Meeting of the Neurogenetics of Drosophila. Coventry, United
      Kingdom, 6-10 September 1998. Abstracts.

PMID- 10917784
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology
      and Nutrition, 1999: presentation.

PMID- 10917785
TI  - The Shwachman Award of the North American Society for Pediatric Gastroenterology
      and Nutrition, 1999: acceptance.

PMID- 10917786
TI  - [Quid?].

PMID- 10917787
TI  - [Congenital aneurysm of the main pulmonary artery].

PMID- 10917788
TI  - The biology of vascular interventions--minimally invasive approaches to vascular
      disease. Research Initiatives in Vascular Disease Conference. Bethesda, Maryland,
      USA. February 17-18, 2000. Abstracts.

PMID- 10917789
TI  - HIV drug resistance.

PMID- 10917790
TI  - From the Centers for Disease Control and Prevention. HIV/AIDS among men who have
      sex with men and inject drugs--United States, 1985-1998.

PMID- 10917791
TI  - From the Centers for Disease Control and Prevention. Adoption of protective
      behaviors among persons with recent HIV infection and diagnosis--Alabama, New
      Jersey and Tennessee, 1997-1998.

PMID- 10917792
TI  - From the Centers for Disease Control and Prevention. Gonorrhea--United States,
      1998.

PMID- 10917793
TI  - JAMA patient page. Avoiding diseases transmitted by blood and body fluids.

PMID- 10917794
TI  - From the Centers for Disease Control and Prevention. Contribution of assisted
      reproduction technology and ovulation-inducing drugs to triplet and higher-order
      multiple births--United States, 1980-1997.

PMID- 10917795
TI  - From the Centers for Disease Control and Prevention. Suspected brucellosis case
      prompts investigation of possible bioterrorism-related activity--New Hampshire
      and Massachusetts, 1999.

PMID- 10917796
TI  - From the Centers for Disease Control and Prevention. Injuries from fireworks in
      the United States.

PMID- 10917797
TI  - JAMA patient page. Gastroesophageal reflux in children.

PMID- 10917799
TI  - Proceedings of the 5th International Conference on Mathematical Population
      Dynamics. Zakopane, Poland, 21-26 June 1998.

PMID- 10917798
TI  - [Allerty and immunological diseases].

PMID- 10917800
TI  - Proceedings of the 1st Congress of the Society of Medical Informatics of Bosnia
      Herzegovina held in Sarajevo on 5 and 6 November 1999.

PMID- 10917801
TI  - Phylogeny of eukaryotes based on ribosomal RNA: long-branch attraction and models
      of sequence evolution.

PMID- 10917814
TI  - [Cardiovascular scientific production in Spain: not all of them are here].

PMID- 10917815
TI  - [Changes en la morphology of the ST segment in Brugada's syndrome].

PMID- 10917816
TI  - Working knowledge. What the well-dressed astronaut wears. A spaceship for one.

PMID- 10917817
TI  - Human genome. Rival genome sequencers celebrate a milestone together.
AB  - At a White House ceremony on 26 June, two scientific groups, one funded by the
      government and the other privately funded, announced that they have generated a
      nearly complete readout of the 3.1 or so billion nucleotides in the human genome.
      The White House ceremony was more than a celebration; it was also designed to
      heal a split in the research community. The ceremony brought together leaders of
      the rival groups in a kind of truce, cooling off a competition that had grown
      intense in recent months.

PMID- 10917818
TI  - Osteoporosis. Cholesterol drugs show promise as bone builders.
AB  - A group of drugs called statins that are used by millions to head off heart
      disease seem not only to prevent fractures, but they may also trigger significant
      bone regrowth, according to four studies reported in the 28 June issue of The
      Journal of the American Medical Association and the 24 June issue of The Lancet.
      And another promising treatment, a recombinant fragment of human parathyroid
      hormone called rhPTH, is even closer to the clinic: Two clinical trials reported
      at meetings in the past 2 weeks show that the compound builds bone and lowers the
      risk of fracture by more than half. These findings could be good news for the
      millions of people worldwide who suffer from osteoporosis.

PMID- 10917819
TI  - European science. Bug Bastille to open under new management.
AB  - In the next few weeks, Europe's most advanced high-security pathogen lab is
      expected to open for business in the southern French city of Lyons, but the long
      anticipated debut of this "hot" lab is not turning out to be a joyous occasion
      for some of those involved. Last week, the Marcel Merieux Foundation, which paid
      for the lab's construction, announced that the Pasteur Institute will take over
      its "scientific direction" and gave Pasteur the authority to name the lab's
      director. The leading candidate is a Pasteur scientist, which would leave the
      lab's current director out in the cold.

PMID- 10917820
TI  - Obesity. Enzyme blocker prompts mice to shed weight.
AB  - A multidisciplinary team may have discovered an important new weapon in the
      battle of the bulge. On page 2379 of this issue, the team reports that a molecule
      that is needed for fat synthesis in the body may play a key role in appetite
      signaling in the brain. Moreover, the investigators produced a synthetic
      inhibitor of this molecule that spurred a dramatic drop in appetite and weight in
      mice.

PMID- 10917821
TI  - Genomics. University company to exploit heart data.
AB  - This month, Boston University, which directs the Framingham Heart Study, a
      massive government effort begun in 1948 to monitor the cardiovascular health of
      more than 10,000 residents of this suburb of Boston, announced plans to form a
      bioinformatics company that will mine the data. The university will own 20% of
      Framingham Genomic Medicine Inc., which hopes to raise $21 million to begin
      modernizing the immense database and packaging it in a format that will be
      valuable to the pharmaceutical industry. The plan raises a host of difficult
      ethical issues, including patient privacy, academic conflicts of interest, and
      reciprocal value to the Framingham residents whose medical data will form the
      basis for the new enterprise.

PMID- 10917822
TI  - Patent disputes. Biotech giants butt heads over cancer drug.
AB  - On 8 June, Chiron challenged Genentech's patent on an important new breast cancer
      drug called Herceptin and sued for a share of the profits. Chiron's 4-page
      complaint, filed in the federal district court in Sacramento, California, accuses
      Genentech of "willful, wanton, and deliberate" infringement of one of its
      patents. The case is being closely watched in the biotech industry not just
      because of the money at stake but also because it involves one of the first
      therapies to emerge from the burgeoning field of cancer genetics

PMID- 10917823
TI  - Human genome. Finally, the book of life and instructions for navigating it.
AB  - The race is over. On 26 June, to much fanfare, two rival teams announced that
      they had each completed a version of the "book of life"--a rough draft of the
      complete human genetic code. So what, exactly, is in these two different volumes,
      and how will they fine-tune it so that everyone from workaday biologists to
      pharmaceutical giants can mine its gold?

PMID- 10917824
TI  - Biotechnology international conference. Biotech research proves a draw in Canada.
AB  - TORONTO, CANADADespite protests from Greenpeace members, some of whom dressed up
      as "corn fakes" to show their opposition to genetically modified organisms, more
      than 500 industrial and academic researchers, lawyers, and business people from
      about 25 countries gathered here from 5 to 8 June for the third biennial
      Agricultural Biotechnology International Conference. Highlights of the meeting
      included reports of progress toward making plants that resist nematode pests or
      stresses such as salt, frost, and drought.

PMID- 10917825
TI  - Infectious diseases. China awakens to fight projected AIDS crisis.
AB  - Official tallies count only 670 confirmed AIDS cases and 18,143 confirmed HIV
      infected people among China's 1.2 billion population. Now changing social mores,
      including an increase in drug use and a boom in commercial sex, combined with a
      tainted blood supply, have led China to the brink of an AIDS explosion. But its
      historic isolation also gives the country an advantage in testing the latest
      vaccines, as the different strains of HIV have not yet commingled there; China's
      well-developed public health infrastructure could also help facilitate clinical
      trials.

PMID- 10917826
TI  - Cloning problems don't surprise plant biologists.

PMID- 10917827
TI  - Lamarck and antibody genes.

PMID- 10917828
TI  - Database searches for binding sites.

PMID- 10917829
TI  - Conservation conundrum.

PMID- 10917830
TI  - Research ethics. Managing risks of arthropod vector research.
AB  - Field research with vectors is an essential aspect of vector biology research and
      vector-borne disease prevention and control. This type of research, which brings
      experimental vector manipulations into endemic areas, can present risks to human
      populations. This paper seeks to stimulate a full discussion within the medical
      entomology community of the risks associated with vector field research. Such
      discussions will promote development of a consensus, among investigators,
      sponsoring agencies and the communities within which the work is done, so that
      appropriate steps can be taken to minimize and manage the risks, and adequate
      oversight can be maintained.

PMID- 10917831
TI  - Redefining virology.
AB  - Viruses have always been classified according to whether their genome is composed
      of DNA or RNA. That may be set to change with the discovery that human
      cytomegalovirus has both a DNA genome and four mRNA transcripts that are produced
      before the DNA genome is transcribed after infection of the host cell (Bresnahan
      and Shenk). As Roizman points out in a lively Perspective, finding out what the
      proteins encoded by these four mRNAs do, and whether other DNA viruses show this
      sneaky partnering of DNA and RNA, will keep virologists busy for many years to
      come.

PMID- 10917833
TI  - AIDS meeting. South African leader declines to join the chorus on HIV and AIDS.

PMID- 10917834
TI  - Ecology. California algae may be feared European species.

PMID- 10917832
TI  - Signal transduction. FasL binds preassembled Fas.
AB  - The binding of a ligand to its receptor has always been viewed as the trigger for
      signal transduction to ensue. However, as Golstein explains in his Perspective,
      new findings (Chan et al. and Siegel et al.) suggest that the Fas receptor
      preassembles into trimers without the help of its ligand, and that this
      preassembly conditions ligand binding, and thus subsequent signal transduction of
      a death signal.

PMID- 10917835
TI  - Scientific publishing. Publish and perish in the Internet world.
AB  - When 120 leaders in publishing and biomedicine met here last week to talk about
      the Internet's effect on scholarly journals, it didn't take long for
      disagreements to surface. Participants clashed over two very different visions of
      the future--one predicting that private firms will continue to produce the most
      reliable and readable journals, the other that scientists will soon abandon
      traditional journals and share results directly with other researchers on the
      Internet.

PMID- 10917836
TI  - Arthritis. A gene for smooth-running joints.
AB  - A new study on page 265 of this issue suggests that a genetic defect in mice
      causes the joint's cartilage cells to pump insufficient amounts of pyrophosphate-
      a natural water softener--into the joint cleft, and this in turn leads to the
      formation of bony spurs that eventually stiffen the joints completely. Because
      humans have an almost identical gene, and disorders such as osteoarthritis also
      feature an abnormal outgrowth of bones, some arthritis researchers are hopeful
      that these new findings may point the way toward a new class of pyrophosphate
      based drugs similar to the antiscaling chemicals in washing powders and
      toothpaste. But, as many of the researchers point out, the numerous roads that
      lead to human joint degradation make a single cure-all unlikely.

PMID- 10917837
TI  - U.K. funding. New program supports facilities, stipends.
AB  - British scientists are celebrating a $1.7 billion windfall, announced last week
      by the U.K. government, to shore up deteriorating facilities and raise stipends
      for Ph.D. students. The 2-year spending boost is intended to keep the pool of
      British science well stocked, both by attracting more talented students into the
      field and stemming the flow of scientists out of the country. But the benefits
      are not spread evenly across the research spectrum.

PMID- 10917838
TI  - Mount Graham. Report finds squirrels survived 3 telescopes.

PMID- 10917839
TI  - European science. Pathogens lab chief stripped of duties.

PMID- 10917840
TI  - Evolutionary biology. Chewed leaves reveal ancient relationship.
AB  - On page 291, researchers describe a new beetle fossil based not on traces of the
      insect skeleton but on the distinctive gouges the beetles left when they munched
      on 11 ginger leaves many millions of years ago. The chew marks of the newly
      described Cephaloleichnites strongi prove that leaf beetles underwent rapid
      evolution and diversification more than 65 million years ago, possibly taking
      advantage of (and perhaps influencing) the rapid diversification among flowering
      plants occurring at the same time. What's more, C. strongi represents the
      earliest known rolled-leaf beetle species, hundreds of which today still prefer
      just one of the ginger- and heliconia-like plants in the Zingiberales order.

PMID- 10917841
TI  - Ecology. When fire ants move in, others leave.
AB  - Researchers have uncovered new evidence about the long-range, and potentially
      long-term, ecological damage being wrought by an invasive species of fire ant.
      The red imported fire ant Solenopsis invicta displaces other ant species and
      upsets the structures of native communities of ants--disruptions that appear to
      be permanent, they report in the July issue of Ecology Letters. The drop in
      biodiversity could represent a significant loss, experts note, because of the
      critical role ants play in recycling nutrients and other biological material.

PMID- 10917842
TI  - Molecular biology. Creation's seventh day.
AB  - Scientists at the Scripps Research Institute are attempting to find out what life
      would look like if DNA contained more than four nucleotide bases and proteins
      more than 20 amino acids. By reengineering DNA, RNA, and the proteins that
      interact with them, they hope to create synthetic organisms with a chemical
      makeup fundamentally different from all life that has existed on Earth for the
      last 3.8 billion years. If they succeed, their biochemical reengineering could
      have a profound effect on everything from basic molecular biology to industrial
      chemistry.

PMID- 10917843
TI  - Molecular biology. Tackling biology with no holds barred, at 800 miles per hour.
AB  - Peter Schultz launched his academic career by exploring what made living
      organisms such powerful synthetic chemists. His work led him to conclude that the
      key to nature's success was its strategy of generating millions of possible
      chemical solutions to a problem and then screening for the ones that worked best.
      Now Schultz is applying this approach to working out the functions of the
      thousands of unknown genes being turned out by the world's genome projects.

PMID- 10917844
TI  - Information science versus science policy.

PMID- 10917845
TI  - Alternative views on alternative medicine.

PMID- 10917846
TI  - Alternative views on alternative medicine.

PMID- 10917847
TI  - Alternative views on alternative medicine.

PMID- 10917848
TI  - Alternative views on alternative medicine.

PMID- 10917849
TI  - Molecular biology. The mad ways of meiosis.
AB  - Reproductive cells that are destined to become sperm or egg undergo meiotic
      division during which the chromosome number is halved. As Sluder and McCollum
      explain in their Perspective, new findings (Shonn et al.) in yeast show that
      there is a spindle checkpoint that operates during meiosis to ensure that an
      equal number of replicated chromosomes arrives at each pole of the cell. One of
      the components of this meiotic spindle checkpoint turns out to be Mad2, which
      gives the signal to halt meiosis if it looks like unequal chromosome segregation
      is taking place.

PMID- 10917850
TI  - Candida's arranged marriage.
AB  - Biologists who study the fungus Candida albicans have always assumed that this
      organism reproduces asexually because they have not found evidence of mating,
      meiosis, or a haploid stage of the life cycle. However, as Gow et al. explain in
      a Perspective, sequencing of the C. albicans genome has revealed the existence of
      a possible mating type locus. This finding has now been extended to demonstrate
      actual mating in the fungus (Hull et al., Magee and Magee).

PMID- 10917851
TI  - Development. p73--guilt by association?
AB  - It has been assumed that the new members of the p53 protein family, p63 and p73,
      would have the same job as p53, namely, forcing cells to die if they or their DNA
      is damaged. Now, as Morrison and Kinoshita explain in their Perspective, one
      particular form of p73 has been found to be a survival factor rather than a death
      factor for sympathetic neurons during development (Pozniak et al.).

PMID- 10917852
TI  - The quickening of science communication.
AB  - In this month's essay, Robert Lucky examines the central sociological impacts
      that communications technologies have had on the way science is done as well as
      the critical influences science has had in the evolution of communications
      technology. He traces the evolution of today's infrastructure for research and
      collaboration in science via the Internet and the World Wide Web back to the
      invention of the telegraph, which first freed the flow of information from its
      reliance on the physical means of transportation and allowed communication to
      occur in real time. According to Lucky, the remaining technical hurdles in
      providing unlimited bandwidth are relatively simple to overcome compared with the
      sociotechnical engineering required to improve the three dimensions of
      communications--human to information, human to human, and human to computer.

PMID- 10917853
TI  - Inhaled fluticasone.

PMID- 10917854
TI  - Gender differences in airway behaviour.

PMID- 10917856
TI  - Diagnosis and assessment of DPLD.

PMID- 10917855
TI  - Cell and cytokine markers in COPD.

PMID- 10917857
TI  - [The pretentions of (animal) doctors].

PMID- 10917858
TI  - [Ten years of veterinary antibiotic policy].

PMID- 10917859
TI  - [Reaction to, 'Ethical guidelines for the association with independent living
      animals in the grounds under State Forest Management'].

PMID- 10917860
TI  - [The establishment of the State Serum Institution and the Health Service for
      Animals].

PMID- 10917861
TI  - Active forces in hearing.

PMID- 10917862
TI  - Cautionary note.

PMID- 10917864
TI  - Physiologically active food components: their role in optimizing health and
      aging. Proceedings of the 17th Ross Research Conference on Medical Issues. San
      Diego, California, USA. February 22-24, 1998.

PMID- 10917863
TI  - [The All-Russian Scientific and Practical Conference on Natural-Focus Infections
      in Russia: the current epidemiology, diagnosis and procedure to protect the
      population].

PMID- 10917865
TI  - Intrarenal endothelin-1 and hypertension.

PMID- 10917866
TI  - What may be done with the jeweled tongue?

PMID- 10917868
TI  - Expression of full-length and truncated recombinant human brain type I inositol
      1,4,5-trisphosphate receptors in mammalian and insect cells.
AB  - Intracellular inositol 1,4,5-trisphosphate receptors (IP(3)Rs) form tetrameric
      Ca2+-release channels that are crucial for Ca2+ signalling in many eukaryotic
      cells. IP(3)R subunits contain an N-terminal, cytoplasmic, ligand binding domain
      linked by a modulatory domain to a channel-forming, hydrophobic C-terminal
      domain. We assembled and sequenced cDNAs encoding the SI-/SII+/SIII+ splice
      variant of the human brain type I IP(3)R, and functionally expressed the full
      length receptor, and a C-terminally truncated receptor lacking the final 20% of
      the protein, in mammalian and insect cells. Both proteins were insoluble,
      consistent with in vivo immunofluorescence and ligand binding studies. This
      contrasted with the behaviour of recombinant FIKBP12 (a soluble control protein).
      The truncated receptor also fractionated with the "membrane" pellet after
      alkaline carbonate treatment. We conclude that the human type I IP(3)R forms high
      MW aggregates or complexes in cells when expressed without the C-terminal
      hydrophobic domain. This behaviour should be considered when expressing and
      refolding "soluble" human type I IP(3)R domains for structural studies.

PMID- 10917869
TI  - The anti-atheroslerotic effect of Allium sativum: statistics re-evaluated.

PMID- 10917870
TI  - Risk of coronary heart disease among Turkish migrants to Germany: further
      epidemiological evidence.

PMID- 10917871
TI  - Whole blood folate, homocysteine in serum, and risk of first acute myocardial
      infarction.

PMID- 10917872
TI  - Upregulation of the interleukin-8 system in hypercholesterolemic patients. Does
      inhibition of the mevalonate pathway lower interleukin-8 levels in the vessel
      wall?

PMID- 10917873
TI  - The chyrnase A(-1903)G gene polymorphism is not associated with the risk and
      extent of coronary heart disease.

PMID- 10917874
TI  - Staphylococcus aureus bacteremia and endocarditis.
AB  - Staphylococcus aureus bacteremia is a serious and common disease often associated
      with infective endocarditis. It occurs in both healthy, immunologically competent
      people in the community and compromised patients in the hospitals. For S. aureus
      bacteremia, questions on clinical issues such as antimicrobial treatment are
      raised. Is nafcillin/oxacillin superior to vancomycin? Does the addition of
      rifampin improve outcome? Does addition of aminoglycoside improve the outcome?
      Does increasing duration of therapy (> 4 weeks versus < 2 weeks) improve outcome?
      How many cases of community-acquired S. aureus bacteremia have endocarditis on
      admission? What are the risk factors that would separate bacteremia from
      endocarditis? What is the role of echocardiography? What are the indications for
      routine echocardiography? Are methicillin-resistant S. aureus (MRSA) more
      virulent than methicillin-susceptible S. aureus (MSSA)? What factors predict
      mortality in S. aureus bacteremia? Herein, the above important issues on S.
      aureus bacteremia and endocarditis are critically reviewed.

PMID- 10917875
TI  - Online identification of viruses.
AB  - A computerized animal virus information system is developed in the Sequence
      Retrieval System (SRS) format. This database is available on the Word Wide Web
      (WWW) at the site http://bioinfo.ernet.in/www/avis/avis++ +.html. The database
      has been used to generate large number of identification matrices for each
      family. The software is developed in C. Unix shell scripts and Hypertext Marked
      up Language (HTML) to assign the family to an unknown virus deterministically and
      to identify the virus probabilistically. It has been shown that such web based
      virus identification approach provides results with high confidence in those
      cases where identification matrix uses large number of independent characters.
      Protein sequence data for animal viruses have been analyzed and oligopeptides
      specific to each virus family and also specific to each virus species are
      identified for several viruses. These peptides thus could be used to identify the
      virus and to assign the virus family with high confidence showing the usefulness
      of sequence data in virus identification.

PMID- 10917876
TI  - Late feeding of dietary fish oil alleviates disease severity and affects
      macrophage function in autoimmune NZB/W F1 mice.
AB  - To investigate the influence of different saturations of dietary fat on
      autoantibody production and disease courses, autoimmune NZB/NZW F1 (NZB/W F1)
      mice were fed diets containing 20% palm oil, lard/soybean oil, soybean oil,
      canola oil or fish oil at 5 months of age. Sera levels of anti-DNA antibodies,
      proteinuria and life span were followed regularly. In addition, peritoneal
      resident cells were isolated and mediators such as interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha), prostaglandin E2 (PGE2) and NO production were
      measured. The results show that mice fed a diet containing with fish oil had
      significantly decreased immunoglobulin G (IgG) anti-single strand (ss) or double
      strand (ds) DNA antibody levels, lessened proteinuria and prolonged life span
      compared to mice fed diets containing other types of dietary fat. TNF-alpha and
      PGE2 levels in mice fed a diet containing fish oil were significantly lower
      compared to the other dietary groups. IL-6 and NO produced by peritoneal resident
      cells were significantly higher in mice fed a diet containing lard/soybean oil in
      comparison with mice of the other groups. Hepatic ex vivo PGE2 level was
      significantly lower in mice fed fish oil compared to mice of the other dietary
      groups. These data suggested that dietary fish oil might affect either
      autoantibody production or macrophage function, contributing to alleviation of
      the autoimmune process in autoimmune-prone NZB/W F1 mice.

PMID- 10917878
TI  - Soluble CD4 suppresses delayed-type hypersensitivity reaction of CD4 loosing mice
      by inhibiting INFgamma production.
AB  - The CD4 loosing (CD4L) mice have a novel defect in CD4 expression where CD4 mRNA
      is alternatively spliced to delete a transmembrane portion to give rise to the
      secretion of soluble CD4 (sCD4) without the expression of membrane-bound CD4. To
      analyze the role of sCD4 in immune responses in CD4L mice, experiments have been
      done by comparing CD4L mice with CD4 knockout (CD4KO) mice on the same C57BL/6
      background. Significantly reduced delayed-type hypersensitivity (DTH) response
      against methylated BSA (mBSA) was found in CD4L mice; however, CD4KO mice showed
      a comparable response to wild type mice. Anti-CD4 treatment in CD4L mice could
      restore DTH response. Moreover, implantation of CD4KO mice with a diffusion
      chamber containing sCD4 secreting cells suppressed DTH response. DTH response
      recovered by anti-CD4 treatment in CD4L mice was inhibited by anti-interferon
      gamma (IFNgamma). IFNgamma production of mBSA-stimulated lymph node cells was
      significantly reduced in CD4L mice as compared with that in CD4KO or wild type
      mice, and the reduction could be recovered by the anti-CD4 treatment. IFNgamma
      production of mBSA-stimulated lymph node cells was suppressed in CD4KO mice
      carrying a diffusion chamber containing sCD4 secreting cells as compared with
      those containing control cells. Taken together, results in this study strongly
      indicate that sCD4 suppresses DTH responses of CD4L mice by inhibiting IFNgamma
      production. The mutant mice could provide a good model to analyze the mechanism
      of IFNgamma involvement in the DTH response.

PMID- 10917877
TI  - Preparation of Der p 1 specific monoclonal antibodies and use in a two-site-ELISA
      to detect Der p 1 allergen.
AB  - It has been well documented that the mite Dermatophoides pteronyssinus (Der p) is
      the major allergen in house dust in Taiwan. The purpose of this study is to
      develop a sandwich immunometric assay which can be used for the standardization
      of mite allergen extracts or house dust, for assessing the procedures of mite
      avoidance, and for identifying species in epidemiological studies. Der p 1
      allergen (both recombinant and native Der p 1) was purified and a panel of Der p
      1 specific monoclonal antibodies was developed. The monoclonal antibodies were
      biotinylated and a two-site enzyme-linked immunosorbent assay (ELISA) with
      peroxidase-conjugated streptavidin was developed for the detection of Der p 1
      allergen. The results suggest that these monoclonal antibodies could be applied
      both in affinity columns for the purification of native Der p 1 antigen and in
      sandwich-ELISA for epidemiological study.

PMID- 10917879
TI  - Characteristics of neonatal bacterial meningitis in a teaching hospital in Taiwan
      from 1984-1997.
AB  - During the period from 1984 to 1997, 85 bacterial meningitis neonates with
      positive cerebrospinal fluid cultures were treated. The ages of these patients
      ranged from 1 to 28 days. The male to female ratio was 1.7 to 1. The most common
      causative agent was group B beta-hemolytic streptococci (GBS, 31.8%), followed by
      Escherichia coli (20%), Proteus mirabilis (7.1%), Enterobacter cloacae (5.9%),
      other streptococci excluding Streptococcus pneumoniae (5.9%), Chryseobacterium
      meningosepticum (5.9%), enterococci (4.7%), and Klebsiella pneumoniae (3.5%).
      Among the 85 patients treated, 51 (60%) were younger than 7 days old. Among them,
      dyspnea was the most common clinical manifestation. In contrast, fever and
      diarrhea were seen more frequently in neonates with late onset of disease (after
      seven days of age). Ampicillin and cefotaxime were the most commonly used
      antibiotics. The most frequently encountered complications were hydrocephalus and
      seizures. Since 1991, GBS has overtaken E. coli as the leading cause of neonatal
      bacterial meningitis. This was accompanied by a fall in the mortality rate, but a
      sustained high incidence of complications and sequelae. The results of this study
      highlight the importance of developing strategies to prevent group B
      streptococcal infection.

PMID- 10917880
TI  - Influenza A virus infection in infants.
AB  - Influenza A virus causes a variety of respiratory and nonrespiratory illness in
      children. The symptomatology varies with different age groups. The purpose of
      this retrospective study was to define the clinical characteristics of influenza
      A infection in Taiwanese infants. During the period from December 1997 to
      February 1998, 37 febrile patients younger than 1 year of age, including five
      newborns, were admitted to our hospital due to suspicion of sepsis or meningitis.
      The medical records of these patients were retrospectively evaluated. Influenza A
      virus was isolated from the specimens of the throat swabs in all patients,
      whereas no bacterial pathogen was detected. The most common clinical
      manifestations of these infants were lower respiratory tract infections,
      including pneumonia, bronchiolitis, and croup. There was no significant
      difference between the clinical characteristics of infants younger than 3 months
      and those aged from 3 months to 1 year. The mean duration of fever, peak of body
      temperature, and duration of hospitalization were 3.41 (+/-1.86) versus 4.4 (+/
      2.02) days, 39.0 (+/-0.57) versus 39.9 (+/-0.63) oC, 4.9(+/-1.49) versus 6.3 (+/
      3.7) days in infants younger than 3 months and infants aged from 3 months to 1
      year, respectively. The older infants aged from 3 months to 1 year had a
      significantly higher peak body temperature than the infants younger than 3 months
      (p < 0.05). Two patients with croup had a more severe clinical course, however,
      the outcomes were good in all patients. During an influenza A virus outbreak,
      influenza A infection should be included in the differential diagnosis of infants
      with lower respiratory tract infection.

PMID- 10917881
TI  - Efficacy and safety of cefepime in the treatment of serious bacterial infections
      in hospitalized adult patients.
AB  - Proper and timely choice of the antibiotic therapy for the management of
      infection in hospitalized patients is an immense challenge to the clinician. A
      newly developed extended-spectrum fourth-generation cephalosporin cefepime, has
      been shown to have good activity against both gram-positive and gram-negative
      organisms. In order to further establish the efficacy and safety of cefepime in
      the treatment of adult hospitalized patients in Taiwan, we reviewed the medical
      records of all patients who received cefepime therapy for more than 72 h at the
      National Taiwan University Hospital during the period from January 1999 to April
      1999. A total of 55 patients were treated with cefepime during this period.
      Thirty-two of them were males and 23 were females. Their ages ranged from 16 to
      94 years old (average, 67). All had severe infections with a mean Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score of 18. More than
      half (56%) of the infections were nosocomial. The most common infections included
      pulmonary infection (49%), intra-abdominal infection (27%), skin and soft tissue
      infection (15%), febrile neutropenia (7%), and intravascular device infection
      (5%). All but one of the patients (98%) had pre-existing medical disease.
      Malignancy (49%) was the most common underlying illness. Pseudomonas aeruginosa
      (23 isolates) and Enterobacter cloacae (21) were the most common pathogens
      causing infections. Thirty-one (58%) of the patients were effectively treated
      with cefepime. Twenty of the patients died during the study period with most
      deaths attributable to persistent microbial infection and superinfection,
      especially Acinetobacter baumannii and fungal infection. Adverse effects
      developed in six patients, including eosinophilia (3 patients), leukopenia (2),
      skin rash (1), and drug related fever (1), but all were mild and transient. The
      results of this study show that cefepime is a safe and effective agent in the
      treatment of adult patients with severe infection in Taiwan.

PMID- 10917882
TI  - Isolation of Aeromonas hydrophila in children with diarrhea.
AB  - Aeromonas species are gram-negative bacilli that lead to a wide spectrum of
      infectious diseases in human. In the present study, these bacilli were reviewed
      to assess their significance as enteric pathogens in this area. During the years
      of 1994 to 1998, the clinical microbiology laboratory received 2150 stool
      specimens of children with diarrhea. Medical charts of patients who had positive
      culture for Aeromonas hydrophila were reviewed. A. hydrophila were isolated from
      50 (2.3%) of 2150 children with diarrhea. Most patients were outpatients with
      ages ranging from 5 months to 16 years old (mean age 3.5 years). The male to
      female ratio was 0.85:1. All patients suffered from watery or loose diarrhea,
      some with blood-tinged stool. Whether or not they received medication, all
      patients had uneventful recoveries. The results of antibiotic susceptibility
      testing revealed that all strains were not susceptible to ampicillin. In summary,
      A. hydrophila may be considered as a causative agent of gastrointestinal illness
      in children.

PMID- 10917883
TI  - Chronic granulomatous disease: a case report.
AB  - Chronic granulomatous disease (CGD) is a rare inherited disorder caused by
      defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      complex of phagocytic leukocytes. The leukocytes of the CGD patients cannot
      produce adequate amount of superoxide and other oxygen metabolites which are
      toxic to microorganisms. As a result, the phagocytes fail to kill the ingested
      microorganisms, especially those with catalase activity. Typically, CGD patients
      suffer from recurrent pyogenic infections starting from the first year of life.
      We report a young boy who had experienced recurrent perianal abscess,
      osteomyelitis and bacterial enterocolitis. Flow cytometric analysis revealed
      defects in the neutrophil respiratory burst pathway and defined the carrier state
      of his mother and younger sister. He received antimicrobial prophylaxis at our
      out-patient clinics and remained well at present. We try to make clinical
      physician keep in mind the diagnosis of CGD by presenting this typical case. In
      the meantime, we review the recent literature regarding the advances in diagnosis
      and management of CGD.

PMID- 10917884
TI  - Comparison of colony lift with direct spotting methods of blot preparation on the
      effect of colony hybridization in the detection of environmental organisms.
AB  - Nucleic acid probes are used on site to detect or to identify individual
      microbial cells without cultivation. This molecular technique can avoid some
      limitations of traditional identification methods including time consuming and
      imprecise. This study examined the factors affecting colony hybridization and
      compared the effectiveness of membrane prepared by colony lifting with direct
      spotting procedures using the universal probe Eub 338. The results of
      hybridization varied depending on the type of colony morphology. For dry and
      rough colonies, colony hybridization was not suitable for detecting
      Acinetobactersp. (CK2A, CK2B), Alcaligenes sp. (TH11 B), Xanthomonas sp. (TH7B),
      Arthrobacter globiformis (CCRC 10598) and Microbacterium sp. (CCRC 11036).
      Colonies of Acinetobacter sp. (CCRC 15425) and Alcaligenes spp. (CCRC 10828, H)
      on agar and membrane were thick and raised, and their detection signals of
      hybridization were diffused or blank. Colonies of Alcaligenes sp. (CM7A, ANV2)
      and Acinetobacter sp. (ANV8) isolated from the sludge of biological processes
      treating ABS wastewater were flat and smooth, and their hybridization signals
      were clear. For those strains suitable for colony hybridization, the colony blots
      prepared by colony lift and direct spotting procedures gave the same sensitivity
      for colony hybridization.

PMID- 10917885
TI  - Application of representational difference analysis to cloning a Mycoplasma
      arthritidis specific DNA fragment.
AB  - Representation difference analysis (RDA) was applied to isolate a Mycoplasma
      arthritidis specific DNA fragment. The DNA fragment obtained was verified to be
      M. arthritidis specific by polymerase chain reaction (PCR) and dot blot
      hybridization tests. The size of this fragment was 194 bp and the nucleotide
      sequence was also determined.

PMID- 10917886
TI  - Schistosoma mansoni infection cancels the susceptibility to Plasmodium chabaudi
      through induction of type 1 immune responses in A/J mice.
AB  - Susceptibility to Plasmodium chabaudi depends on the relative dominance of
      T(h)1/T(h)2 responses in host mice. A T(h)2-dominant response during the early
      phase of infection in susceptible A/J mice causes a fatal disease course due to
      severe malaria. Schistosoma mansoni is a potent inducer of a T(h)2-dominant
      response not only to the parasite antigens, but also to other antigens
      concurrently existing in the host animals. In spite of S. mansoni infection,
      these A/J mice escape death from malaria and showed accompanied enhanced
      production of IFN-gamma to malaria antigens. Treatment with anti-IFN-gamma mAb in
      S. mansoni-infected A/J mice abolished the resistance to malaria, indicating that
      IFN-gamma was responsible for the resistance to P. chabaudi in S. mansoni
      infected A/J mice. Results in this study show that under certain circumstances,
      S. mansoni infection can promote type 1 immune responses in A/J mice that
      normally develop T(h)2 responses.

PMID- 10917887
TI  - Effect of murine thymic epithelial cell line (MTEC1) on the functional expression
      of CD4(+)CD8(-) thymocyte subgroups.
AB  - To determine the effect of thymic stromal cells on the functional maturation of
      CD4 single-positive (SP) thymocytes, the functional status of isolated CD4 SP
      thymocyte subgroups was investigated by means of cell proliferation and cytokine
      production in response to concanavalin A (Con A) prior and after co-culturing
      with a murine thymic epithelial cell line (MTEC1). Mouse medullary CD4 SP
      thymocytes were phenotypically divided into seven discrete subgroups predicted to
      reflect the maturation pathway from newly emerging CD4 SP thymocytes to
      terminally differentiated cells. For functional analysis, six major subgroups
      (6C10(+)CD69(+), 6C10(-)CD69(+), 6C10(-)CD69(-)3G11(+)Qa-2(-), 6C10(-)CD69(
      )3G11(+)Qa-2(+), 6C10(-)CD69(-)3G11(-)Qa-2(-) and 6C10(-)CD69(-)3G11(-)Qa-2(+))
      cells were isolated and their functional status in response to Con A stimulation
      assessed. A functional hierarchy is revealed among these subgroups, consistent
      with their phenotypic maturation status, which may imply that these cells undergo
      a functional maturation process within thymic medulla. The function of cytokine
      production by CD4 SP thymocytes is acquired in a stepwise manner from a low to
      high level and characterized by T(h)0-type cytokines in the main stream of
      differentiation pathway. However, a minor subgroup that appeared at the late
      stage as 3G11(-)6C10(-) cells was biased to produce T(h)2-type cytokines.
      Nevertheless, the functional capacity of the final two Qa-2(+) subgroups of CD4
      SP thymocytes was still significantly lower than that of spleen CD4(+) T cells.
      After co-cultivation with MTEC1 cells, four subgroups of
      TCRalphabeta(+)CD4(+)CD8(-) thymocytes exhibited significantly higher levels of
      proliferation capability and modulation in cytokine production capability.
      However, co-culturing with MTEC1 cells did not change the pattern of T(h)0- or
      T(h)2-like cytokine production by respectively medullary CD4 SP thymocyte
      subgroups nor could MTEC1 induce CD4 SP thymocytes to secrete T(h)1-type
      cytokines. The results suggest that MTEC1 can regulate the functional status of
      these thymocyte subgroups.

PMID- 10917888
TI  - Properties of HLA class II molecules divergently associated with Goodpasture's
      disease.
AB  - Goodpasture's disease provides an opportunity to analyse molecular mechanisms
      that may underlie MHC class II associations with autoimmune disease because it is
      caused by autoimmunity to a defined antigen [the 230 amino acid NC1 domain of the
      alpha3 chain of type IV collagen (alpha3(IV)NC1)] and has strong HLA class II
      associations. We compared the alpha3(IV)NC1 peptide binding of class II molecules
      with strong positive (DR15) and dominant negative (DR7/1) associations using an
      inhibition binding assay and short synthetic peptides spanning the sequence of
      alpha3(IV)NC1. DR15 in general bound the peptides with low affinity (three of 23
      < 100 nM) compared to DR1 and DR7 (12 and 10 < 100 nM respectively), and no
      peptide bound DR15 with much higher affinity (>10-fold) than both DR1 and DR7.
      Thus DR15 molecules are unlikely to increase susceptibility to Goodpasture's
      disease by presenting a particular alpha3(IV)NC1-derived peptide uniquely well
      and DR1/7 are unlikely to protect by their inability to present particular
      peptides. However DR1/7 could protect by capturing alpha3(IV)NC1 peptides and
      preventing their display bound to DR15; the binding data suggest that all the
      major (biochemically detectable) alpha3(IV)NC1 peptides presented bound to DR15
      by DR15 homozygous antigen-presenting cells (APC) would bind preferentially to
      DR1/7 in DR15, 1/7 heterozygote APC.

PMID- 10917889
TI  - Naturally anergic and suppressive CD25(+)CD4(+) T cells as a functionally and
      phenotypically distinct immunoregulatory T cell subpopulation.
AB  - A CD4(+) T cell subpopulation defined by the expression levels of a particular
      cell surface molecule (e.g. CD5, CD45RB, CD25, CD62L or CD38) bears an autoimmune
      preventive activity in various animal models. Here we show that the expression of
      CD25 is highly specific, when compared with other molecules, in delineating the
      autoimmune-preventive immunoregulatory CD4(+) T cell population. Furthermore,
      although CD25 is an activation marker for T cells, the following findings
      indicate that immunoregulatory CD25(+)CD4(+) T cells are functionally distinct
      from activated or anergy-induced T cells derived from CD25(-)CD4(+) T cells.
      First, the former are autoimmune-preventive in vivo, naturally unresponsive
      (anergic) to TCR stimulation in vitro and, upon TCR stimulation, able to suppress
      the activation/proliferation of other T cells, whereas the latter scarcely
      exhibit the in vivo autoimmune-preventive activity or the in vitro suppressive
      activity. Second, such activated or anergy-induced CD25(-) spleen cells produce
      various autoimmune diseases when transferred to syngeneic athymic nude mice,
      whereas similarly treated normal spleen cells, which include CD25(+)CD4(+) T
      cells, do not. Third, upon polyclonal T cell stimulation, CD25(+)CD4(+) T cells
      express CD25 at higher levels and more persistently than CD25(-)CD4(+) T cell
      derived activated T cells; moreover, when the stimulation is ceased, the former
      revert to the original levels of CD25 expression, whereas the latter lose the
      expression. These results collectively indicate that naturally anergic and
      suppressive CD25(+)CD4(+) T cells present in normal naive mice are functionally
      and phenotypically stable, distinct from other T cells, and play a key role in
      maintaining immunologic self-tolerance.

PMID- 10917890
TI  - Structure of celiac disease-associated HLA-DQ8 and non-associated HLA-DQ9 alleles
      in complex with two disease-specific epitopes.
AB  - The association of celiac disease (CD) with HLA-DQ2 and HLA-DQ8 is indicative of
      preferential mucosal T cell recognition of gluten fragments bound to either DQ
      allele. We have recently identified two gluten-derived, HLA-DQ8-restricted T cell
      stimulatory peptides, one each from gliadin and glutenin, recognized by specific
      T cell clones derived from the small intestine of CD patients. We have now
      performed molecular modeling and examined the fine specificity of these peptides
      in complex with HLA-DQ8. There is only one binding register for both peptides,
      with glutamine residues at the p1 and p9 anchor positions. Both T cell clones
      recognize substituted peptides at p1 and p9, but poorly so at p2-p8, especially
      the gliadin-specific clone. Contrasting patterns of recognition of p9Gln --> Glu
      peptide variants (both predicted as better DQ8 binders by modeling) were
      observed: enhancement of recognition for the gliadin peptide, yet complete
      absence thereof for the glutenin peptide. The double-substituted gliadin peptide
      variant p1/9Gln --> Glu, which can also arise by pepsin/acid/transglutaminase
      treatment, shows a considerable increase in sensitivity of recognition,
      consistent with better binding of this peptide to DQ8, as predicted by energy
      minimization. Surprisingly, the two native peptides are also recognized by their
      respective T cell clones in the context of the related molecule HLA-DQ9
      (beta57Asp(+)). The p1/9Gln --> Glu gliadin peptide variant is likewise
      recognized, albeit with a 10-fold lower sensitivity, the first reported p9Glu
      binding in a beta57Asp(+) MHC II allele. Our results have important implications
      for the pathogenesis of autoimmune disease and the possible manipulation of
      aberrant responses thereof.

PMID- 10917891
TI  - NF-kappaB/p50 and NF-kappaB/c-Rel differentially regulate the activity of the
      3'alphaE-hsl,2 enhancer in normal murine B cells in an activation-dependent
      manner.
AB  - The enhancer complex located 3' to the C(H)alpha gene in the IgH locus (3alphaE)
      may regulate B cell function through its ability to act as a locus control
      region. Multiple, functionally relevant NF-kappaB binding sites are located
      within the 3'alphaE. NF-kappaB subunits, especially p50 and c-Rel, have also been
      shown to play critical and differential roles in regulating B cell proliferation,
      Ig secretion, germline C(H) transcription and Ig class switching. Thus, NF-kappaB
      could regulate B cell function in part through modulation of 3'alphaE activity.
      In this study we determined whether p50 and/or c-Rel regulate 3'alphaE activity
      in normal murine B cells and whether this depends on the nature of the B cell
      activator. For this purpose, we crossed p50- and c-Rel-deficient mice with mice
      that are transgenic for a 3'alphaE-hsl,2-human beta-globin reporter gene, and
      established p50(-/-) or c-Rel(-/-) mice homozygous for the enhancer transgene. We
      show, using optimal stimulating conditions, that p50 selectively augments 3'alpha
      E-hsl,2 activity in lipopolysaccharide-activated B cells, whereas c-Rel is
      required for optimal 3'alphaE-hs1,2 induction in B cells activated through CD40.

PMID- 10917892
TI  - RANTES activates antigen-specific cytotoxic T lymphocytes in a mitogen-like
      manner through cell surface aggregation.
AB  - RANTES (regulated upon activation, normal T cell expressed and secreted) is
      released by cytotoxic T lymphocytes (CTL), and is a potent chemoattractant factor
      for monocytes and T cells, also known for its ability to suppress HIV infection.
      At micromolar concentration, RANTES is able to activate leukocytes, and,
      paradoxically, to enhance HIV infection in vitro. These latter properties are
      dependent on its ability to self-aggregate. In order to understand further the
      mechanism of RANTES-induced activation, the effects of both aggregated and
      disaggregated RANTES on antigen-specific CD8(+) clones were studied in comparison
      with the effects of specific antigens and in the presence of specific inhibitors
      of RANTES-mediated activation. We observed large amounts of RANTES aggregated on
      the cell surface, which led to cell activation, including up-regulation of cell
      surface markers, and secretion of IFN-gamma and macrophage inflammatory protein
      (MIP)-1beta. Specific inhibitors of RANTES-induced activation, such as soluble
      glycosaminoglycans, MIP-1alpha and MIP-1beta, acted by preventing the binding of
      RANTES on the cell surface. These studies suggest that RANTES acted more like a
      mitogen than an antigen-independent activator.

PMID- 10917893
TI  - Proteolytic cleavage of beta(2)-glycoprotein I: reduction of antigenicity and the
      structural relationship.
AB  - Binding of beta(2)-glycoprotein I (beta(2)-GPI)-dependent anticardiolipin
      antibodies (aCL) derived from antiphospholipid syndrome (APS) is significantly
      reduced in aCL ELISA due to loss of the phospholipid (PL) binding property of
      beta(2)-GPI by plasmin treatment. In the present study, the treatment generated a
      nicked form of beta(2)-GPI and resulted in loss of antigenicity for the
      autoantibodies detected in ELISA, using an beta(2)-GPI directly adsorbed
      polyoxygenated carboxylated plate, the assay system of which was not related to
      PL binding. The nicked form bound to neither Cu(2+)-oxidized low-density
      lipoprotein (oxLDL) nor to beta(2)-GPI-specific lipid ligands isolated from
      oxLDL, the result being a complete loss of subsequent binding of anti-beta(2)-GPI
      autoantibodies. The conformational change in the nicked domain V was predicted
      from its intact structure determined by an X-ray analysis (implemented in Protein
      Data Bank: 1C1Z), molecular modeling and epitope mapping of a monoclonal anti
      beta(2)-GPI antibody, i.e. Cof-18, which recognizes the related structure. The
      analysis revealed that novel hydrophobic and electrostatic interactions appeared
      in domain V after the cleavage, thereby affecting the PL binding of beta(2)-GPI.
      Such a conformational change may have important implications for exposure of
      cryptic epitopes located in the domains such as domain IV.

PMID- 10917894
TI  - Murine gamma-herpesvirus infection causes V(beta)4-specific CDR3-restricted
      clonal expansions within CD8(+) peripheral blood T lymphocytes.
AB  - Infection of mice with the gamma-herpesvirus MHV-68 results in lytic infection in
      the lung cleared by CD8(+) cells and establishment of lifelong latency. An
      Epstein-Barr virus (EBV)-like infectious mononucleosis (IM) syndrome emerges
      approximately 3 weeks after infection. In human IM, the majority of T cells in
      the peripheral blood are monoclonal or oligoclonal and are frequently specific
      for lytic or latent viral epitopes. However, a unique feature of MHV-68-induced
      IM is a prominent MHC haplotype-independent expansion of CD8(+) T cells, the
      majority of which utilize V(beta)4 chains in their alphabetaTCR. The ligand
      driving the V(beta)4 expansion is unknown, but the V(beta) bias and MHC haplotype
      independence raised the possibility that these cells were responding to a virally
      encoded or a virally induced endogenous superantigen (sAg). The aim of this study
      was to determine whether this rapidly proliferating subset is composed of
      polyclonally or clonally expanded T cells. Complementarity-determining region
      (CDR)-3 size analysis of V(beta)4(+)CD8(+) cells in infected mice demonstrated
      CDR3-restricted expansions in the V(beta)4 family as a whole. More refined
      analysis demonstrated major distortions in every J(beta) subfamily. V-D-J
      junctional region sequencing indicated that these CDR3 size-restricted expansions
      were composed of clonal or oligoclonal populations. The sequences were largely
      unique in individual mice, although evidence for 'public' or highly conserved T
      cell expansions was also seen between different mice. Taken together with
      previous studies showing an apparent MHC independence, the data suggest that a
      novel ligand, distinct from conventional sAg and peptide-MHC, drives
      proliferation of V(beta)4(+)CD8(+) T cells.

PMID- 10917895
TI  - Molecular mechanism of the impairment in activation signal transduction in CD4(+)
      T cells from old mice.
AB  - It is well known that IL-2 production of CD4(+) T cells from old mice (old T
      cells) is impaired. In this study, we have examined TCR complex zeta chain
      expression of old T cells and their TCR downstream signal transduction pathways
      stimulated with anti-CD3. Activation of protein tyrosine kinases, Fyn and ZAP-70,
      and turnover of inositol phosphates stimulated with anti-CD3 were severely
      impaired in old T cells, although levels of these proteins were comparable to
      those in young T cells. Increase in intracellular Ca2+ concentration in old T
      cells was also impaired. Old T cells starting the Ca(2+) oscillation by the anti
      CD3 stimulation were severely decreased in number and the oscillation waves were
      broader in shape. T cells with zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3
      complex were increased in proportion in old T cells with a concomitant decrease
      in the T cells with zeta-zeta homodimer. The density of the TCR-CD3 complex on
      old T cells was confirmed to be comparable to that on young T cells. The
      impairment in TCR downstream signal transduction pathways and the increase in
      zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3 complex were confirmed to be
      the situation in Th1 clones established from old mice. These results indicate
      that old T cells are impaired in response to TCR stimulation, because T cells
      with the TCR-CD3 complex containing the zeta-FcvarepsilonRgamma heterodimer are
      increased in proportion in old T cells.

PMID- 10917896
TI  - The vitamin K-dependent carboxylase.
AB  - The carboxylase is an integral membrane glycoprotein that uses vitamin K to
      modify clusters of glutamyl residues (glu's) to gamma-carboxylated glutamyl
      residues (gla's) post-translationally in vitamin K-dependent (VKD) proteins as
      they pass through the endoplasmic reticulum. Carboxylation is required for VKD
      protein functions in hemostasis, bone metabolism, growth control and signal
      transduction. Carboxylation of multiple glu residues is accomplished via a
      processive mechanism, which occurs with at least some order and involves
      carboxylation of the carboxylase. The carboxylase has a high affinity binding
      site for VKD proteins, which in most cases is a VKD propeptide sequence; it also
      appears to have a low affinity site for those glu's undergoing catalysis. The
      propeptide activates binding of the glu's; together, the two contact points
      between the carboxylase and VKD protein increase the affinity of the carboxylase
      for vitamin K. Biochemical mapping to identify where these events occur in the
      carboxylase remains a challenge, despite the availability of recombinant protein.
      The affinity of the carboxylase for the propeptide of several VKD proteins that
      are coexpressed in liver varies over a 100-fold range. Treatment with
      anticoagulants such as warfarin that indirectly block carboxylation likely
      decreases the rate of VKD protein catalysis and increases the accumulation of VKD
      precursors, leading to a competitive state among these proteins, which results in
      the premature dissociation of undercarboxylated, inactive protein.

PMID- 10917897
TI  - Dietary studies related to the United States diet prior to World War II: a
      bibliography for the study of changing American food habits over time.
AB  - Dietary studies from the early part of the 20th century are a rich source of
      information about the dietary habits of the people and the science of nutrition.
      This annotated bibliography is meant to facilitate access to this part of the
      historical literature for further study.

PMID- 10917898
TI  - Isoflavone aglycone-rich extract without soy protein attenuates atherosclerosis
      development in cholesterol-fed rabbits.
AB  - The antiatherogenic effect of soy protein with intact isoflavones is well
      established, but the effects of isoflavones without soy protein have not been
      determined. We investigated the antiatherogenic effect of an isoflavone aglycone
      rich extract (containing 429.4 mg/g isoflavone aglycones) without soy protein
      from fermented soy in cholesterol-fed rabbits. We fed 12-wk-old New Zealand white
      male rabbits diets containing 1 g/100 g cholesterol with 0, 0.33 or 1 g/100 g
      isoflavone aglycones for 8 wk. We also fed the rabbits a diet containing 1 g/100
      g cholesterol with 1.09 g/100 g soy saponin-rich extract, a component other than
      isoflavone aglycones in the isoflavone aglycone-rich extract. Controls did not
      consume cholesterol, isoflavone aglycones or saponins. The isoflavone aglycone-
      and saponin-rich extracts did not affect the serum lipid profile of cholesterol
      fed rabbits. The serum concentration of daidzein in its conjugated form was
      significantly higher in the high isoflavone group than in the low isoflavone
      group. The level of cholesteryl ester hydroperoxide (ChE-OOH) induced by CuSO(4)
      in plasma in the high isoflavone group was significantly less than that in the
      cholesterol group, and the ChE-OOH levels of LDL in the low and high isoflavone
      groups were significantly less than those in the cholesterol group. The ChE-OOH
      levels in plasma and LDL in the saponin group did not differ from the cholesterol
      group. In the aortic arch, the cholesterol concentration was significantly lower
      in the high isoflavone group, and malondialdehyde concentration was significantly
      lower in the low and high isoflavone groups compared with the cholesterol group;
      however these concentrations in the saponin group did not differ from those in
      the cholesterol group. The atherosclerotic lesion area of the aortic arch was
      significantly lower in the isoflavone groups (26.3% lower in the low isoflavone
      group and 36.9% lower in the high isoflavone group) than in the cholesterol
      group. The lesion areas were not different in the soy saponin and cholesterol
      groups. Immunohistochemical analysis revealed fewer oxidized LDL-positive
      macrophage-derived foam cells in atherosclerotic lesions in the aortic arch of
      isoflavone groups compared with that of the cholesterol group. These results
      suggest that the antioxidative action of isoflavones and their antioxidative
      metabolites inhibit the oxidation of LDL, thereby exerting an antiatherosclerotic
      effect.

PMID- 10917900
TI  - Metallothionein in mice reduces intestinal zinc loss during acute endotoxin
      inflammation, but not during starvation or dietary zinc restriction.
AB  - Normal metallothionein [(MT)+/+] and MT-null (MT-/-) mice were used to examine
      the influence of MT on Zn retention and the metabolic consequences of 2 d food
      deprivation, with and without inflammation induced by intraperitoneal injection
      of bacterial endotoxin lipopolysaccharide (LPS). LPS reduced fecal Zn
      concentration in MT+/+ mice from 5.9 +/- 0.2 micromol/g on d 1 to 2.2 +/- 0.2
      micromol/g on d 2, but not in MT-/- mice, 5.9 +/- 0.2 and 5.7 +/- 0. 5
      micromol/g, respectively. MT+/+ mice fed an 8 mg Zn/kg diet and injected with LPS
      excreted 40% less Zn over 2 d than their MT-/- counterparts. Starvation for 2 d
      did not lower fecal Zn concentration in either genotype, although in MT+/+ mice,
      urinary Zn excretion was reduced from 12.7 +/- 1.3 nmol on d 1 to 5.9 +/- 1.8
      nmol on d 2 and plasma Zn concentration was lowered to 9.8 +/- 0.4 micromol/L. Zn
      was not reduced in urine or plasma of MT-/- mice, with respective values of 10.8
      +/- 2.0 nmol on d 1, 9.3 +/- 2.9 nmol on d 2 and 13.0 +/- 1.0 micromol/L. LPS
      injection resulted in much higher total liver Zn (677 +/- 27 nmol) and MT (106 +/
      2 nmol Cd bound/g) than starvation (Zn = 405 +/- 21, MT = 9 +/- 3) in MT+/+ mice
      after 2 d, but did not further reduce urinary Zn. LPS-injected MT-/- mice had no
      rise in liver Zn or fall in plasma and urine Zn. MT-/- mice fed a Zn-deficient
      (0.8 mg Zn/kg) diet lost 10% of body weight over 25 d compared with no loss in
      MT+/+ mice. Despite this, MT-/- mice excreted no more Zn via the gut than did
      MT+/+ mice. In summary, MT inhibits intestinal Zn loss when highly expressed.
      When uninduced, typically during Zn deficiency, MT appears to conserve Zn and
      body mass by reducing only urinary and other nonintestinal Zn losses.

PMID- 10917899
TI  - Extremely low activity of methionine synthase in vitamin B-12-deficient rats may
      be related to effects on coenzyme stabilization rather than to changes in
      coenzyme induction.
AB  - Severely vitamin B-12 (B-12)-deficient rats were produced by feeding a B-12
      deficient diet. The status of B-12 deficiency was confirmed by an increase in
      urinary methylmalonate excretion and decreases in liver B-12 concentrations and
      cobalamin-dependent methionine synthase activity. Rat liver methionine synthase
      existed almost exclusively as the holoenzyme. In B-12-deficient rats, the level
      of methionine synthase protein was lower, although the mRNA level was not
      significantly different from that of control rats. When methylcobalamin, the
      coenzyme for methionine synthase, was administered to the B-12-deficient rats,
      growth, liver B-12 concentrations and urinary excretion of methylmalonate were
      reversed although not always to control (B-12-sufficient) levels in a short
      period. During this recovery process, methionine synthase activity and its
      protein level increased, whereas the mRNA level was unaffected. We reported
      previously that rat apomethionine synthase is very unstable and is stabilized by
      forming a complex with methylcobalamin. Thus, the extremely low activity of
      methionine synthase in B-12-deficient rats may be related to effects on "coenzyme
      stabilization" (stabilization of the enzyme by cobalamin binding) rather than to
      changes in "coenzyme induction."

PMID- 10917901
TI  - Dietary beta-carotene stimulates cell-mediated and humoral immune response in
      dogs.
AB  - The role of beta-carotene on immune response in domestic dogs is not known.
      Female Beagle dogs were fed 0, 2, 20 or 50 mg beta-carotene/d; blood was sampled
      at wk 0, 1, 2, 4 and 8 for analysis of the following: lymphoproliferation,
      leukocyte subpopulations and concentrations of interleukin-2 (IL-2),
      immunoglobulin (Ig)G and IgM. Delayed-type hypersensitivity (DTH) response was
      assessed at wk 0, 3 and 7. beta-Carotene supplementation increased plasma beta
      carotene concentrations in a dose-dependent manner. Compared with unsupplemented
      dogs, those fed 20 or 50 mg of beta-carotene had higher CD4+ cell numbers and
      CD4:CD8 ratio. However, there was no treatment difference in CD8+, CD21+ and
      major histocompatability complex (MHC) class II+ cells. Plasma IgG, but not IgM
      concentration was higher in dogs fed beta-carotene throughout the study period.
      The DTH response to phytohemagglutinin (PHA) and vaccine was heightened in beta
      carotene-supplemented dogs. beta-Carotene feeding did not influence mitogen
      induced lymphocyte proliferation or IL-2 production. Immune response was impaired
      in dogs classified as low beta-carotene absorbers compared with similar dogs fed
      the same amount of beta-carotene. Therefore, dietary beta-carotene heightened
      cell-mediated and humoral immune responses in dogs.

PMID- 10917902
TI  - The trans-10,cis-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA
      desaturase 1 gene expression in 3T3-L1 adipocytes.
AB  - Conjugated linoleic acids (CLA) are a group of positional and geometric
      conjugated dienoic isomers of linoleic acid. The objective of this study was to
      determine the effects of the cis-9,trans-11 and trans-10,cis-12 isomers of
      conjugated linoleic acid on lipid composition and gene expression during the
      differentiation of mouse 3T3-L1 preadipocytes. Treatment of differentiating 3T3
      L1 preadipocytes with trans-10,cis-12 conjugated linoleic acid (CLA) resulted in
      a dose-dependent decrease in the expression of the stearoyl-CoA desaturase 1 gene
      (SCD1). The expression of other adipocyte genes such as adipose P2 (aP2), fatty
      acid synthase (FAS), SCD2 and the key adipogenic transcription factors,
      peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and CCAAT enhancer
      binding protein alpha (C/EBPalpha), remained elevated. Cells treated with trans
      10,cis-12 CLA exhibited smaller lipid droplets, with reduced levels of the major
      monounsaturated fatty acids, palmitoleate and oleate. By contrast, the cis
      9,trans-11 isomer did not alter adipocyte gene expression. Repression of the
      stearoyl-CoA desaturase gene expression in adipocytes by the trans-10,cis-12
      isomer may contribute to the mechanisms by which CLA reduces body fat in mice.

PMID- 10917903
TI  - Addition of eicosapentaenoic acid to gamma-linolenic acid-supplemented diets
      prevents serum arachidonic acid accumulation in humans.
AB  - Previous studies reveal that supplementation of human diets with gamma-linolenic
      acid (GLA) reduces the generation of lipid mediators of inflammation and
      attenuates clinical symptoms of chronic inflammatory disorders such as rheumatoid
      arthritis. However, we have shown that supplementation with this same fatty acid
      also causes a marked increase in serum arachidonate (AA) levels, a potentially
      harmful side effect. The objective of this study was to design a supplementation
      strategy that maintained the capacity of GLA to reduce lipid mediators without
      causing elevations in serum AA levels. Initial in vitro studies utilizing HEP-G2
      liver cells revealed that addition of eicosapentaenoic acid (EPA) blocked Delta-5
      desaturase activity, the terminal enzymatic step in AA synthesis. To test the in
      vivo effects of a GLA and EPA combination in humans, adult volunteers consuming
      controlled diets supplemented these diets with 3.0 g/d of GLA and EPA. This
      supplementation strategy significantly increased serum levels of EPA, but did not
      increase AA levels. EPA and the elongation product of GLA, dihomo-gamma-linolenic
      acid (DGLA) levels in neutrophil glycerolipids increased significantly during the
      3-wk supplementation period. Neutrophils isolated from volunteers fed diets
      supplemented with GLA and EPA released similar quantities of AA, but synthesized
      significantly lower quantities of leukotrienes compared with their neutrophils
      before supplementation. This study revealed that a GLA and EPA supplement
      combination may be utilized to reduce the synthesis of proinflammatory AA
      metabolites, and importantly, not induce potentially harmful increases in serum
      AA levels.

PMID- 10917904
TI  - Different substrates and methane producing status affect short-chain fatty acid
      profiles produced by In vitro fermentation of human feces.
AB  - Five different substrates, i.e., lactulose, rhamnose, cornstarch, guar and
      ileostomy effluent, were used to determine whether methane producing status
      alters the production of short-chain fatty acids (SCFA) in methane producers (MP;
      n = 6) and nonproducers (MNP; n = 5). Fecal samples from MP and MNP were
      fermented with the five substrates using an in vitro fermentation method.
      Subjects with a mean breath methane concentration > 0.045 micromol/L above
      ambient air were classified as MP. Fermentation was stopped and samples were
      obtained at 3, 5 and 24 h. An HPLC method was used to measure the SCFA, acetate,
      propionate, isobutyrate, butyrate, valerate and isocaproate. A significant
      interaction between methane producing status and time for acetate production from
      lactulose was observed. There were no differences in fermentation of the four
      remaining substrates between MP and MNP, but there were significant differences
      among substrates in the two groups combined. Acetate production from lactulose
      was significantly greater than from the four other substrates, whereas that from
      ileostomy effluent was significantly less than the four other substrates. The
      amount of propionate produced from rhamnose was significantly higher than from
      the other substrates. The amount of butyrate produced from lactulose and
      cornstarch was significantly higher than from the other substrates. We conclude
      that differences exist in the fermentation patterns of lactulose, rhamnose,
      cornstarch, guar and ileostomy effluent. Methane producing status may influence
      fermentation patterns only of substrates that are largely fermented to acetate
      and not others.

PMID- 10917905
TI  - beta-hydroxy-beta-methylbutyrate (HMB) supplementation in humans is safe and may
      decrease cardiovascular risk factors.
AB  - The leucine metabolite, beta-hydroxy-beta-methylbutyrate (HMB) enhances the
      effects of exercise on muscle size and strength. Although several reports in
      animals and humans indicate that HMB is safe, quantitative safety data in humans
      have not been reported definitively. The objective of this work was to summarize
      safety data collected in nine studies in which humans were fed 3 g HMB/d. The
      studies were from 3 to 8 wk in duration, included both males and females, young
      and old, exercising or nonexercising. Organ and tissue function was assessed by
      blood chemistry and hematology; subtle effects on emotional perception were
      measured with an emotional profile test (Circumplex), and tolerance of HMB was
      assessed with a battery of 32 health-related questions. HMB did not adversely
      affect any surrogate marker of tissue health and function. The Circumplex emotion
      profile indicated that HMB significantly decreased (improved) one indicator of
      negative mood (Unactivated Unpleasant Affect category, P < 0.05). No untoward
      effects of HMB were indicated. Compared with the placebo, HMB supplementation
      resulted in a net decrease in total cholesterol (5.8%, P < 0.03), a decrease in
      LDL cholesterol (7.3%, P < 0.01) and a decrease in systolic blood pressure (4.4
      mm Hg, P < 0.05). These effects of HMB on surrogate markers of cardiovascular
      health could result in a decrease in the risk of heart attack and stroke. In
      conclusion, the objective data collected across nine experiments indicate that
      HMB can be taken safely as an ergogenic aid for exercise and that objective
      measures of health and perception of well-being are generally enhanced.

PMID- 10917906
TI  - Blood glucose and insulin concentrations are reduced in humans administered
      sucrose with inosine or adenosine.
AB  - Recently we found that some nucleosides such as inosine or adenosine inhibited
      alpha-glucosidase from rat intestine. The aim of this study was to determine
      whether these nucleosides are sucrase inhibitors in humans as well as rats. Blood
      glucose and insulin responses were examined in 23 healthy volunteers (18 males
      and 5 females) administered sucrose with inosine and 8 (males) administered
      sucrose with adenosine. The initial increase in plasma glucose and serum insulin
      concentrations at 30 min after loading sucrose (50 g) alone were significantly
      reduced by co-administration of inosine (2.5 and 1.0 g) or adenosine (2.5 g). The
      total increases in the areas under the plasma glucose and serum insulin
      concentration curves for 3 h after administration of the same amount of sucrose
      with inosine were also significantly less than those when the volunteers were
      administered sucrose alone. These results in humans agree with the findings
      obtained in our previous studies in rats. These nucleosides may be used as one of
      the components of artificial sweeteners when mixed with sucrose and may be useful
      as food additives to suppress increases in blood glucose and insulin.

PMID- 10917907
TI  - Nutritional factors and infectious disease contribute to anemia among pregnant
      women with human immunodeficiency virus in Tanzania.
AB  - The objective of this cross-sectional study was to identify risk factors for
      anemia among human immunodeficiency virus (HIV)-positive pregnant women in Dar es
      Salaam, Tanzania. Baseline data from 1064 women enrolled in a clinical trial on
      the effect of vitamin supplementation in HIV infection were examined to identify
      potential determinants of anemia. The mean hemoglobin (Hb) level was 94 g/L, and
      the prevalence of severe anemia (Hb < 85 g/L) was 28%; 83% of the women had Hb <
      110 g/L. Iron deficiency and infectious disease appeared to be the predominant
      causes of anemia. Significant independent associations with severe anemia were
      observed for women with body mass index (BMI) < 19 kg/m(2) compared with women
      with BMI > 24 kg/m(2) [odds ratio (OR) 3.13, 95% confidence interval (CI): 1. 37
      7.14); malaria parasite densities > 1000/mm(3) (OR 2.70, CI: 1. 58-4.61) compared
      with women with no parasites; eating soil during early pregnancy (OR 2.47, CI:
      1.66-3.69); CD4+ cell count < 200/microL compared with CD4+ count > 500/microL
      (OR 2.70, CI: 1. 42-5.12); and serum retinol levels < 70 micromol/L (OR 2.45, CI:
      1. 44-4.17) compared with women with retinol levels > 1.05 micromol/L. The most
      significant risk factors associated with severe anemia in this population are
      preventable. Public health recommendations include increasing the effectiveness
      of iron supplementation and malaria management during pregnancy, and providing
      health education messages that increase awareness of the potentially adverse
      nutritional consequences of eating soil during pregnancy.

PMID- 10917908
TI  - The metabolic availability of vitamin A is decreased at the onset of diabetes in
      BB rats.
AB  - Streptozotocin (STZ)-induced diabetic rats have been associated with an impaired
      metabolic availability of vitamin A (retinol). This study was undertaken to
      investigate whether Biobreeding (BB) rats, in which diabetes mellitus resembling
      human type I diabetes develops spontaneously, respond the same way at the onset
      of diabetes. Weaning diabetes-prone (BBdp) and normal (BBn) BB rats consumed NIH
      07 nonpurified diet ad libitum until 120 d of age. Plasma and hepatic
      concentrations of retinol and its carriers, retinol-binding protein (RBP) and
      transthyretin (TTR) were lower in diabetic BB (BBd) rats than in BBn rats. In
      parallel with RBP, the abundance of mRNA was lower in the liver of BBd rats.
      Furthermore, the status of zinc, an important factor for the synthesis of RBP,
      was also disturbed in BBd rats, as indicated by lower circulatory levels and
      greater urinary excretion. To determine whether the biochemical evidence of
      vitamin A deficiency in BBd rats could be reversed, BBdp rats were fed a diet
      supplemented with vitamin A either alone or in combination with zinc. None of
      these treatments increased plasma vitamin A concentration. The hepatic abundance
      of RBP mRNA was significantly greater, whereas circulatory RBP concentrations
      were unaffected by vitamin A plus zinc supplementation. Overall, these results
      suggest that impaired metabolic availability of vitamin A, possibly caused by its
      decreased transport from hepatic stores, is another metabolic derangement
      associated with type I diabetes.

PMID- 10917909
TI  - Mass spectrometric determination of Genistein tissue distribution in diet-exposed
      Sprague-Dawley rats.
AB  - Genistein, the principal soy isoflavone, was administered in the diet to male and
      female Sprague-Dawley rats as part of a multigeneration study of potential
      endocrine modulation. The rats were exposed to genistein in utero, through
      maternal milk, and as adults through postnatal d 140 via essentially isoflavone
      free feed (approximately 0.5 microg/g) fortified at 5, 100 and 500 microg/g with
      genistein aglycone. Analytical methods based on liquid chromatography, mass
      spectrometry and the use of deuterated genistein were developed and validated for
      use in measuring genistein in serum and tissues. Pharmacokinetic analysis of
      serum genistein showed a significant difference (P < 0.001) in the elimination
      half-life and area under the concentration-time curve between male [2.97 +/- 0.14
      h and 22.3 +/- 1.2 micromol/(L. h), respectively] and female rats [4.26 +/- 0.29
      h and 45.6 +/- 3.1 micromol/(L. h), respectively, +/- SEM]. Endocrine-responsive
      tissues including brain, liver, mammary, ovary, prostate, testis, thyroid and
      uterus showed significant dose-dependent increases in total genistein
      concentration. Female liver contained the highest amount of genistein (7.3
      pmol/mg tissue) and male whole brain contained the least (0.04 pmol/mg). The
      physiologically active aglycone form was present in tissues at fractions up to
      100%, and the concentration was always greater than that observed in serum in
      which conjugated forms predominated (95-99%). These results for measured amounts
      of genistein, present as aglycone and conjugates, in putative target tissues
      provide a link with other studies in which blood concentrations and physiologic
      effects of genistein are measured.

PMID- 10917910
TI  - Urea production is increased in neonatal piglets infused with alanine at 25, 50,
      and 75% of resting energy needs .
AB  - To study the ability of neonatal piglets to metabolize a nitrogen load and
      excrete it as urea, 12 newborn piglets, 6 small (0.99 +/- 0. 16 kg; expt. 1) and
      6 large (1.86 +/- 0.16 kg; expt. 2), were infused intravenously with alanine (n =
      8; 4 large, 4 small; treatment) or glucose (n = 4; 2 large, 2 small; control) at
      equal ATP equivalents, supplying 25-75% of the resting energy requirements of the
      piglet over 18 h. To adjust for differences in the baseline urinary urea nitrogen
      excretion, blood urea nitrogen (BUN) and estimated urea production between
      groups, the absolute changes from baseline to maximum value for piglets infused
      with alanine, and from baseline to the 24-h value for piglets infused with
      glucose were evaluated statistically. There were no differences (0.1 < P < 0.3)
      in the absolute changes from baseline to maximum values of urinary urea nitrogen,
      BUN or estimated urea production between small [18.6 +/- 3.8 mg N/(h. kg(0.75));
      19.1 +/- 2.2 mmol N/L; 2.7 +/- 1.2 mmol N/(h. kg(0.75)), respectively] and large
      [23.6 +/- 7.6 mg N/(h. kg(0. 75)); 21.6 +/- 3.3 mmol N/L; 3.7 +/- 1.5 mmol N/(h.
      kg(0.75)), respectively] piglets infused with alanine. Differences in the changes
      from baseline were detected between alanine and glucose (P = 0.001) infusions.
      Small piglets required more time (P < 0.005) for BUN to maximize after initiation
      of the alanine infusion, suggesting that small piglets require more time to
      process a nitrogen load. Infusion of alanine resulted in at least a threefold
      increase from baseline in the rate of calculated urea production, suggesting that
      neonatal piglets, small or large, have reserve capacity to metabolize nitrogen
      and excrete it as urea.

PMID- 10917911
TI  - Comparison of total body urea production potential with total body carbamoyl
      phosphate synthetase (CPS-1) activity in newborn piglets infused with alanine at
      50% of resting energy expenditure for 36 hours.
AB  - The calculated rate of urea production [U(p); mmol urea/(h. kg(0. 75))], based on
      urinary urea-N (UUN) excretion and changes in total body urea-N, was compared
      with the calculated total body V(max) of carbamoyl phosphate synthetase (CPS-1)
      of 24 neonatal piglets from four treatments as follows: 6 h baseline control (n =
      8), 18 h of alanine intravenously (IV) at 50% of resting energy expenditure (REE;
      n = 4), 36 h of alanine IV at 50% of REE (n = 6), or 36 h of glucose IV at 50% of
      REE (n = 6). The following significant increases from baseline were seen in
      piglets infused with alanine for 36 h: 1) UUN excretion [10.6 +/- 5.9 mg N/(h.
      kg(0.75)) to 53.2 +/- 11.1]; 2) BUN concentrations (9.1 +/- 3.0 mmol urea N/L to
      51.2 +/- 7.0); 3) calculated urea production [0.34 +/- 0.21 mmol urea/(h.
      kg(0.75)) to 2.39 +/- 0.53]; and 4) CPS-1 V(max) [2.0 +/- 0.81 mmol
      citrulline/(h. kg (0.75)) to 4.4 +/- 1.5], (P < 0.05). With the exception of CPS
      1 activity, significant decreases from baseline were seen in these values in
      piglets infused with glucose for 36 h (P < 0.05). Comparison of calculated urea
      production with calculated total body CPS-1 V(max) at baseline, 18 or 36 h after
      the start of infusion of alanine or glucose revealed a positive relationship
      (slope = 0.263; P < 0.002). At all enzyme activities, infusion of alanine
      resulted in a significant increase in the rate of urea production compared with
      controls (P < 0.001). Total body CPS-1 activity varied from 1.8 to 5.8 times that
      of urea production, suggesting that CPS-1 did not limit urea production.

PMID- 10917912
TI  - Arabinoxylan fiber from a by-product of wheat flour processing behaves
      physiologically like a soluble, fermentable fiber in the large bowel of rats.
AB  - Arabinoxylan is a major dietary fiber component of many cereals. Its
      physiological effects in the colon are largely unknown. This study examined the
      effects of an arabinoxylan-rich fiber (AX) extracted from a by-product of wheat
      flour processing in the rat colon compared with well-characterized
      soluble/rapidly fermentable and insoluble/slowly fermentable fibers. Rats were
      fed diets containing no fiber (NF) or 100 g/kg of total dietary fiber from AX,
      guar gum (GG) or wheat bran (WB) for 4 wk. Cecal mass and short-chain fatty acid
      (SCFA) pool were significantly higher while pH was significantly lower in the
      fiber-supplemented groups, particularly in the AX and GG groups. The pattern of
      SCFA production in the cecum was altered; AX fiber was a good source for acetate
      while GG and WB favored propionate and butyrate production, respectively. Fecal
      output was 7-, 6- and 5-fold higher, respectively, in the AX, GG and WB than in
      the NF groups (P < 0.01). All epithelial proliferation indices (crypt column
      height, number of mitotic cells/crypt column and mitotic index) differed
      significantly across the groups in a descending order of AX > GG > WB > NF.
      Distal mucosal dipeptidyl peptidase IV activities, which indicate cell
      differentiation status, were significantly lower in fiber-supplemented groups
      than in the NF groups. Distal mucosal alkaline phosphatase activities, induced as
      a response to injury or stress, were significantly higher for the AX and GG
      groups than for the NF or WB groups (P < 0.001). These results indicate that AX
      fiber behaves like a rapidly fermentable, soluble fiber in the rat colon.

PMID- 10917913
TI  - Fermentation of resistant rice starch produces propionate reducing serum and
      hepatic cholesterol in rats.
AB  - This study was designed to investigate the effects of different proportions of
      rice starch and cornstarch on lipid metabolism in rats fed high dietary
      cholesterol. Male Wistar rats were fed a 10 g/100 g fat diet containing 1 g/100 g
      cholesterol with 0 (control diet), 15, 30, 45 or 63 g/100 g rice starch with an
      enzyme resistant starch concentration of 1.26, 1.39, 1.52, 1.65 or 1.80 g/100 g,
      respectively, for 4 wk. Groups fed diets with < 63 g/100 g rice starch were
      supplemented with cornstarch to 63 g/100 g. The two kinds of starch had different
      structures as seen using scanning electron microscopy (SEM). The rice starch was
      an aggregation (n = 20-60) of smaller granules (3-8 microm in diameter), whereas
      the cornstarch was composed of larger (5-15 microm in diameter), single granules.
      The compound rice starch (0.99 kg/L) was larger in size and denser in structure
      than cornstarch (0.63 kg/L). Serum total cholesterol concentrations in rats fed
      both the 45 and 63 g/100 g rice starch diets were significantly lower than in all
      other groups (P < 0.05). The serum propionate concentration in the rats fed 63
      g/100 g rice starch diets was significantly higher than that of other groups.
      Hepatic triglyceride and total cholesterol concentrations in rats fed 63 g/100 g
      rice starch diets were significantly lower than in the control group. These
      results suggest that, because the compound rice starch was an aggregation of
      smaller granules, larger in size and denser in structure than cornstarch, it was
      digested more slowly and altered lipid metabolism. Resistant rice starch may be
      fermented to produce propionate, which reduces serum and hepatic cholesterol.

PMID- 10917914
TI  - beta-carotene is converted primarily to retinoids in rats in vivo.
AB  - beta-Carotene might be converted oxidatively to vitamin A- active products in
      animals by the following three possible routes: 1) central cleavage, 2)
      sequential excentric cleavage or 3) random cleavage. Central cleavage is strongly
      favored by stoichiometric studies with tissue homogenates in vitro. To examine
      the relative importance of these pathways in rats in vivo, an oral dose (5.6
      micromol) of all-trans beta-carotene in oil was given to vitamin A-deficient (-A)
      and to vitamin A-sufficient (+A) adult female Sprague-Dawley rats. Serum and
      several tissues were analyzed before and 3 h after dosing. The primary products
      of beta-carotene found in the intestine, serum and liver were retinol, retinyl
      esters and retinoic acid. Two minor oxidation products of beta-carotene, namely,
      5,6-epoxy-beta-carotene and a partially characterized hydroxy-beta-carotene, were
      present in the stomach and its contents as well as in intestinal preparations. In
      the intestine, including its contents, of -A rats, very minor amounts of 5,6
      epoxyretinyl palmitate and of beta-apocarotenals (8', 10', 12', 14') were
      identified. The total amount of the beta-apocarotenoids, however, was <5% of the
      retinoids formed in the intestine from beta-carotene during the same period.
      Another beta-carotene derivative, with a spectrum similar to that of semi-beta
      carotenone, citranaxanthin and beta-apo-6'-carotenal, was also found in the
      intestinal extract of a -A rat. beta-Apocarotenals, beta-apocarotenols, beta
      apocarotenyl esters and beta-apocarotenoic acids were not detected in tissues of
      +A rats nor in other tissues of -A rats. These findings agree with the view that
      central cleavage is by far the major pathway for the formation of vitamin A from
      beta-carotene in healthy rats in vivo.

PMID- 10917915
TI  - Isomers of conjugated linoleic acid (CLA) are incorporated into egg yolk lipids
      by CLA-fed laying hens.
AB  - This study was designed to determine the amount of conjugated linoleic acid (CLA)
      incorporated into egg lipids after dietary CLA supplementation. Single Comb White
      Leghorn laying hens (n = 40; 28 wk old) were randomly assigned to four treatments
      of varying CLA levels (0, 0.01, 0.5 and 1 g CLA/kg diet). Eggs were collected
      daily for 36 d. Feed consumption and body weight were monitored. CLA content of
      egg yolk lipid was analyzed by gas-liquid chromatography. Birds fed 0.5 and 1.0 g
      CLA/kg feed had significantly more CLA in the egg yolk lipid vs. control and 0.01
      g CLA/kg diet groups after 7 d (P < 0.0004). Incorporation of CLA into egg lipid
      was highest on d 24 and 36. CLA enrichment in egg lipid in the 1.0 g CLA/kg diet
      group was similar to that in ruminant animal food products, approximately 3 mg
      CLA/g fat.

PMID- 10917916
TI  - Inhibition of enzymic digestion of amylose by free fatty acids in vitro
      contributes to resistant starch formation.
AB  - The effect of lipids on the enzymic breakdown of starch was investigated using an
      in vitro assay system. Mixtures of potato amylose, amylopectin and starch and
      various lipids were incubated at 37 degrees C for 10 min and subjected to
      digestion by alpha-amylase (EC 3.2.1.1) and amyloglucosidase (EC 3.2.1.33).
      Lauric, myristic, palmitic and oleic acids and lysolecithin inhibited enzymic
      hydrolysis of amylose by approximately 35% (P < 0.05). Stearic acid and
      cholesterol had no effect on the enzymic breakdown of amylose. Retrograded
      amylose was hydrolyzed less readily (P < 0.05) than solubilized amylose, but the
      breakdown was not further inhibited in the presence of lauric acid. Fatty acids
      had no effect on the enzymic hydrolysis of amylopectin, whereas inhibition by
      fatty acids of the breakdown of whole starch was consistent with only the amylose
      fraction being affected. The possibility that interactions between starch and
      fatty acids in the digestive tract could contribute to the formation of resistant
      starch is considered.

PMID- 10917917
TI  - Tricaproin, tricaprin and trilaurin are utilized more efficiently than
      tricaprylin by carp (Cyprinus carpio L.) larvae.
AB  - We investigated the effect of chain length of dietary medium-chain fatty acids
      (MCFA) on growth performance and fatty acid composition of first-feeding carp
      larvae. In a first trial, five semi-purified isolipidic (23-24 g/100 g of dry
      matter) diets were formulated to contain either 10 g/100 g triolein (control
      diet) or 5 g/100 g triolein and 5 g/100 g medium-chain triacylglycerols (MCT)
      supplied as tricaproin, tricaprylin, tricaprin or trilaurin. After 21 d, survival
      and growth rates were significantly greater in larvae fed diets containing
      triolein, tricaproin, tricaprin and trilaurin (final survival: 92 +/- 7% and mean
      larval weight: 42 +/- 15 mg) than in larvae fed tricaprylin (final survival: 56
      +/- 12% and mean larval weight: 15 +/- 1 mg). The recovered levels of the fed
      MCFA in larval total lipids were respectively 0, 1.3, 7.3 and 8.1 g/100 g of
      total fatty acids. In a second trial, two isolipidic (18 g/100 g) diets
      containing 10 g/100 g triolein or tricaprylin were tested. High amounts of capric
      acid (up to 25 g/100 g of total fatty acids) were found in neutral lipids of carp
      larvae fed tricaprylin for 11 d, suggesting an unusual elongation of caprylic
      acid. This study underlines the peculiarity of tricaprylin among other MCT which
      seem well utilized up to 20-30 g/100 g of total dietary fatty acids. The
      exception of tricaprylin raises the question of the metabolic pathways followed
      by this MCT, especially for the suggested direct elongation of caprylic acid into
      capric acid.

PMID- 10917918
TI  - Dietary plasma protein is used more efficiently than extruded soy protein for
      lean tissue growth in early-weaned pigs.
AB  - We compared the effects of supplementing either animal plasma or extruded soy
      protein in the diet based on the efficiency of dietary protein utilization for
      lean tissue growth in early-weaned pigs. Twenty-four 14-d-old pigs (4 kg body
      weight) were pair-fed (per kg body weight) either a control diet containing
      extruded soy protein (C; n = 12) or a diet with 10% animal plasma (P; n = 12) for
      24 d. During the 24 days, protein intake was not different, yet mean daily body
      weight gains (+23%) and food conversion efficiencies (expressed as the ratio of
      body weight gain to protein intake) (+19%) were greater (P < 0.05) in the P group
      than in the C group. Lean body mass measured after 24 d, using both dual-energy X
      ray absorptiometry and total body potassium analysis, was significantly (P <
      0.05) greater (approximately 16%) in P than in C pigs. The circulating urea
      concentrations were 40% lower (P < 0.05) in P than in C pigs. Our results
      demonstrate that supplementing early-weaned pig diets with animal plasma rather
      than extruded soy protein increased the efficiency of dietary protein use for
      lean tissue growth and that this response is mediated in part by decreased amino
      acid catabolism.

PMID- 10917919
TI  - Dietary phytic acid and wheat bran enhance mucosal phytase activity in rat small
      intestine.
AB  - The aim of this work was to investigate the influence of dietary phytic acid (PA)
      on intestinal phytase activity in growing rats by in vitro determination of
      phytase activity in the three segments of the small intestine (duodenum, jejunum
      and ileum), and by in vivo intestinal perfusion of a solution rich in PA (diluted
      soymilk). Using the in vitro method, duodenal and jejunal activities were
      enhanced significantly by adaptation to purified PA (+44 and +145% respectively,
      compared with control rats). For the rats adapted to the wheat bran (WB) diet,
      the induction of intestinal phytase by the substrate compared with the control
      values (P < 0.001) was observed only in ileum. Using soymilk in perfusions, rats
      consuming PA or WB diets hydrolyzed more phytate (P < 0.001 and P < 0.05,
      respectively) than controls. Further, Mg absorption from diluted soymilk was not
      affected by food adaptation, whereas Ca absorption was greater in the PA and WB
      groups (P < 0.001 and P < 0.05, respectively) than in the control group. Thus,
      intake of pure PA by rats enhances phytase in the upper parts of the small
      intestine (duodenum and jejunum), whereas the WB diet activates ileal phytase.
      Furthermore, the induction of phytase activity is greater in magnitude in rats
      fed synthetic PA than that observed in rats fed the WB diet. The enhancement of
      phytase improves intestinal Ca absorption, thus showing the capacity of the small
      intestine to adapt to diets rich in PA and poor in Ca.

PMID- 10917920
TI  - Protein-bound D-amino acids, and to a lesser extent lysinoalanine, decrease true
      ileal protein digestibility in minipigs as determined with (15)N-labeling.
AB  - Heat and alkali treatment of food may increase the concentrations of protein
      bound D-amino acids and cross-links such as lysinoalanine (LAL). To examine how
      protein treatment affects digestibility, purified test meals [total protein 150
      g/kg dry matter (DM), 0.44 MJ/(kg BW(0.75). d)] were prepared, containing (g/kg
      DM) casein, 75; beta-lactoglobulin, 50; or wheat protein, 40. Each was (15)N
      labeled. Test proteins were used either in their native form or after treatment
      for 6 or 24 h at 65 degrees C, pH 10.5-11.5. Each meal was fed to nine adult
      miniature pigs (twofold complete cross-classification). Chyme was collected
      continuously over 33 h postprandially via T-fistulas in the terminal ileum, and
      digestibilities of test proteins and individual L- and D-amino acids were
      calculated on the basis of recovery of (15)N and the respective amino acids in
      the chyme. Treatment of casein, beta-lactoglobulin or wheat protein for 24 h
      increased levels of D-amino acid residues. L-Asparagine and aspartate (L-Asx)
      were particularly susceptible; 14. 7 +/- 0.4, 11.7 +/- 0.2 and 11.0 +/- 0.9%,
      respectively, underwent racemization. LAL levels increased in parallel; 11.7 +/-
      0.3, 13.6 +/- 0 and 14.8 +/- 0.0%, respectively, of total lysine was converted to
      LAL. At the same time, prececal protein digestibility was decreased by 13.4 +/-
      2.3, 15.3 +/- 1.4 and 17.8 +/- 1.2% units, respectively (P < 0.05; mean +/- SEM,
      n = 9). Digestibility of individual L-amino acids decreased by 10-15%, but L
      amino acids prone to peptic cleavage, such as L-phenylalanine and L-tyrosine,
      were not affected. Digestibilities of D-amino acids and LAL were approximately
      35%. It seems that mainly D-amino acids, and to a lesser extent LAL, were
      responsible for lower digestibility by interfering with peptic cleavage.

PMID- 10917921
TI  - High dietary manganese lowers heart magnesium in pigs fed a low-magnesium diet.
AB  - Young pigs were fed a diet moderately high or low in manganese (Mn) (0.95 +/-
      0.10 mmol Mn/kg, n = 8 or 0.040 +/- 0.003 mmol Mn/kg, n = 6) and deficient in
      magnesium (Mg) (4.1 mmol Mg/kg) for 5 wk. All eight pigs consuming the high Mn
      diet died following convulsive seizures, whereas only two of six died in the
      group fed low Mn. In an attempt to determine the cause of death, a subsequent
      study examined the interactive effect of deficient dietary Mg and Mn on the
      tissue distribution of Mg and Mn. Pigs were individually fed, for 5 wk, diets
      that contained: 4.1 mmol Mg/kg and 36.0 micromol Mn/kg, 4.1 mmol Mg/kg and 0.91
      mmol Mn/kg, 4.1 mmol Mg/kg and 0.91 mmol Mn/kg with added ultratrace minerals, or
      41.1 mmol Mg/kg and 0. 91 mmol Mn/kg, and ultratrace minerals. Liver and skeletal
      muscle Mn concentrations were significantly elevated by increased dietary Mn.
      Increased dietary Mn did not affect heart Mn, but heart Mg concentrations were
      significantly depressed by high, as compared to low, dietary Mn (38.7 +/- 3.3 vs.
      32.7 +/- 2.6 mmol Mg/kg). These data suggest high dietary Mn may exacerbate Mg
      deficiency in heart muscle and thus may be a complicating factor in the deaths
      observed in Mg-deficient pigs.

PMID- 10917922
TI  - Linoleic acid conjugation by human intestinal microorganisms is inhibited by
      glucose and other substrates in vitro and in gnotobiotic rats.
AB  - The anticarcinogen conjugated linoleic acid (CLA) is a product of bacterial
      activity that isomerizes linoleic acid (LA) in the rumen of herbivores.
      Therefore, fatty dairy products in the human diet are enriched with CLA. Although
      bacteria capable of in vitro LA conjugation were detected in the human intestinal
      tract, CLA synthesis from dietary sunflower seed oil was not observed in
      gnotobiotic rats associated with these intestinal bacteria. The objective of the
      study was to investigate variables that affect LA conjugation. In vitro, LA
      conjugation was strongly inhibited by glucose and other substrates.
      Concentrations of 1.5 mmol glucose/L inhibited LA conjugation by 50%. Methyl
      alpha-D-glucoside was a less effective inhibitor than glucose, and 2-deoxy-D
      glucose did not inhibit LA conjugation at all. To analyze the concentration of
      carbohydrates in intestinal contents, the LA-conjugating bacterial mixed culture
      and human fecal microorganisms were introduced into germ-free rats. Samples of
      feces and cecum and colon contents of both groups exhibited in vitro LA
      conjugating activity. Rats associated with human intestinal microorganisms
      contained 5.7 +/- 1. 3 mmol glucose/L in the cecal contents and 6.6 +/- 1.0 mmol
      glucose/L in the colonic contents. Rats associated with CLA-producing bacterial
      culture contained 3.4 +/- 1.3 mmol glucose/L in the cecal contents and 4.2 +/-
      1.0 mmol glucose/L in the colonic contents. These values are within a range that
      may explain the observed inhibition of LA conjugation in vivo.

PMID- 10917923
TI  - Chronic marginal iron intakes during early development in mice alter brain iron
      concentrations and behavior despite postnatal iron supplementation.
AB  - The objective of this study was to investigate the behavioral and cognitive
      outcomes associated with chronic marginal iron (Fe) intakes during early
      development. Offspring (3 males and 3 females/litter) of Swiss-Webster female
      mice who had been fed a control Fe diet (75 microg Fe/g diet) or marginal Fe diet
      (14 microg Fe/g diet) for 9 wk before mating were weaned on postnatal (PND) 21.
      Offspring of marginal Fe dams were fed either the marginal Fe diet (marginal
      group) or a control diet (replete group) from PND 21 throughout the duration of
      the study, whereas offspring of control dams consumed the control diet ad libitum
      (control group). On PND 30, 45 and 60, one male and female per litter underwent
      grip strength and auditory startle testing. A Morris maze was used to assess
      cognitive function in males starting at PND 50. Marginal Fe mice consistently
      demonstrated significantly lower grip strength, which was independent of
      differences in body weight. In addition, marginal Fe males demonstrated
      attenuated startle responsiveness, as well as altered performance in the Morris
      water maze. These differences in performance were found in association with lower
      brain Fe concentrations. Postnatal Fe supplementation did not reverse all of
      these disturbances because differences in brain Fe concentrations and maze
      learning persisted. This study demonstrates that chronic marginal Fe intakes
      during early development can result in persistent biochemical and behavioral
      changes in mice.

PMID- 10917924
TI  - Underreporting of food intake by dietary recall is not universal: a comparison of
      data from egyptian and american women.
AB  - Underreporting of dietary intake has been observed consistently in food
      consumption surveys in affluent societies and in clinical studies in a variety of
      settings. Almost one third of quantitative 24-h recalls provided by adults in
      U.S. surveys appear to result in estimates that are biologically implausible.
      Underreporting has been linked to obesity in both the U.S. and Europe, with
      heavier individuals underreporting to a greater degree than lean persons. A
      relative dearth of data exists from developing countries and those in transition
      to address the question whether such underreporting is universal. We present the
      first data from a large survey of women in a rapidly urbanizing developing
      country to address this question. More than 4500 adult women in Egypt provided
      quantitative 24-h recalls of food intake on the previous day in 1993-1994, and
      weights and heights were measured. We compared the data, in terms of the ratio of
      reported energy intake to estimated basal metabolic rate, to data from 3010 women
      in the 1994-1996 U.S. Continuing Survey of Food Intake by Individuals, on whom
      quantitative 24-h recalls were also conducted. The Egyptian women reported food
      intakes consistent with FAO/WHO recommendations for energy intakes for women of
      comparable activity levels, whereas the data for U.S. women showed underreporting
      consistent with other U.S. surveys. Only 10% of Egyptian women reported energy
      intakes below accepted criteria for plausibility, compared with one third of
      American women. We discuss possible reasons for this difference, including
      cultural and food supply differences, and methodological differences between the
      two surveys.

PMID- 10917925
TI  - Food of the gods: cure for humanity? A cultural history of the medicinal and
      ritual use of chocolate.
AB  - The medicinal use of cacao, or chocolate, both as a primary remedy and as a
      vehicle to deliver other medicines, originated in the New World and diffused to
      Europe in the mid 1500s. These practices originated among the Olmec, Maya and
      Mexica (Aztec). The word cacao is derived from Olmec and the subsequent Mayan
      languages (kakaw); the chocolate-related term cacahuatl is Nahuatl (Aztec
      language), derived from Olmec/Mayan etymology. Early colonial era documents
      included instructions for the medicinal use of cacao. The Badianus Codex (1552)
      noted the use of cacao flowers to treat fatigue, whereas the Florentine Codex
      (1590) offered a prescription of cacao beans, maize and the herb tlacoxochitl
      (Calliandra anomala) to alleviate fever and panting of breath and to treat the
      faint of heart. Subsequent 16th to early 20th century manuscripts produced in
      Europe and New Spain revealed >100 medicinal uses for cacao/chocolate. Three
      consistent roles can be identified: 1) to treat emaciated patients to gain
      weight; 2) to stimulate nervous systems of apathetic, exhausted or feeble
      patients; and 3) to improve digestion and elimination where cacao/chocolate
      countered the effects of stagnant or weak stomachs, stimulated kidneys and
      improved bowel function. Additional medical complaints treated with
      chocolate/cacao have included anemia, poor appetite, mental fatigue, poor breast
      milk production, consumption/tuberculosis, fever, gout, kidney stones, reduced
      longevity and poor sexual appetite/low virility. Chocolate paste was a medium
      used to administer drugs and to counter the taste of bitter pharmacological
      additives. In addition to cacao beans, preparations of cacao bark, oil (cacao
      butter), leaves and flowers have been used to treat burns, bowel dysfunction,
      cuts and skin irritations.

PMID- 10917926
TI  - Dietary intake and bioavailability of polyphenols.
AB  - The main dietary sources of polyphenols are reviewed, and the daily intake is
      calculated for a given diet containing some common fruits, vegetables and
      beverages. Phenolic acids account for about one third of the total intake and
      flavonoids account for the remaining two thirds. The most abundant flavonoids in
      the diet are flavanols (catechins plus proanthocyanidins), anthocyanins and their
      oxidation products. The main polyphenol dietary sources are fruit and beverages
      (fruit juice, wine, tea, coffee, chocolate and beer) and, to a lesser extent
      vegetables, dry legumes and cereals. The total intake is approximately 1 g/d.
      Large uncertainties remain due to the lack of comprehensive data on the content
      of some of the main polyphenol classes in food. Bioavailability studies in humans
      are discussed. The maximum concentration in plasma rarely exceeds 1 microM after
      the consumption of 10-100 mg of a single phenolic compound. However, the total
      plasma phenol concentration is probably higher due to the presence of metabolites
      formed in the body's tissues or by the colonic microflora. These metabolites are
      still largely unknown and not accounted for. Both chemical and biochemical
      factors that affect the absorption and metabolism of polyphenols are reviewed,
      with particular emphasis on flavonoid glycosides. A better understanding of these
      factors is essential to explain the large variations in bioavailability observed
      among polyphenols and among individuals.

PMID- 10917927
TI  - Procyanidin content and variation in some commonly consumed foods.
AB  - Procyanidins are a subclass of flavonoids found in commonly consumed foods that
      have attracted increasing attention due to their potential health benefits.
      However, little is known regarding their dietary intake levels because detailed
      quantitative information on the procyanidin profiles present in many food
      products is lacking. Therefore, the procyanidin content of red wine, chocolate,
      cranberry juice and four varieties of apples has been determined. On average,
      chocolate and apples contained the largest procyanidin content per serving (164.7
      and 147.1 mg, respectively) compared with red wine and cranberry juice (22.0 and
      31.9 mg, respectively). However, the procyanidin content varied greatly between
      apple samples (12.3-252.4 mg/serving) with the highest amounts on average
      observed for the Red Delicious (207.7 mg/serving) and Granny Smith (183.3
      mg/serving) varieties and the lowest amounts in the Golden Delicious (92.5
      mg/serving) and McIntosh (105.0 mg/serving) varieties. The compositional data
      reported herein are important for the initial understanding of which foods
      contribute most to the dietary intake of procyanidins and may be used to compile
      a database necessary to infer epidemiological relationships to health and
      disease.

PMID- 10917928
TI  - Cocoa procyanidins and human cytokine transcription and secretion.
AB  - We examined whether cocoa, in its isolated procyanidin fractions (monomer through
      decamer), would modulate cytokine production at the levels of transcription and
      protein secretion in both resting and phytohemagglutinin (PHA)-stimulated
      peripheral blood mononuclear cells (PBMC). In resting cells, interleukin (IL)
      1beta and IL-4 gene expression from cocoa-treated cells varied markedly among the
      subjects tested. However, at the protein level, the larger fractions (pentamer
      through decamer) stimulated a dramatic increase in IL-1beta concentration (up to
      ninefold) with increasing degree of polymerization. Similarly, these larger
      fractions augmented IL-4 concentration by as much as 2 pg/ml, whereas the control
      displayed levels nearly undetectable. In the presence of PHA, gene expression
      also seemed to be most affected by the larger procyanidin fractions. The
      pentameric through decameric fractions increased IL-1 beta expression by 7-19%
      compared with PHA control, whereas the hexameric through decameric fractions
      significantly inhibited PHA-induced IL-4 transcription in the range of 71-86%.
      This observation at the transcription level for IL-1 beta was reflected at the
      protein level in PHA-stimulated PBMC. Significant reductions in mitogen-induced
      IL-4 production were also seen at the protein level with the hexamer, heptamer
      and octamer. Individual oligomeric cocoa fractions were unstimulatory for IL-2 in
      resting PBMC. However, when induced with PHA, the pentamer, hexamer and heptamer
      fractions caused a 61-73% inhibition in IL-2 gene expression. This study offers
      additional data for the consideration of the health benefits of dietary
      polyphenols from a wide variety of foods, including those benefits associated
      specifically with cocoa and chocolate consumption.

PMID- 10917929
TI  - Reactions of peroxynitrite with cocoa procyanidin oligomers.
AB  - Peroxynitrite is a mediator molecule in inflammation, and its biological
      properties are being studied extensively. Flavonoids, which are natural plant
      constituents, protect against peroxynitrite and thereby could play an anti
      inflammatory role. Procyanidin oligomers of different sizes (monomer through
      nonamer), isolated from the seeds of Theobroma cacao, were recently examined for
      their ability to protect against peroxynitrite-dependent oxidation of
      dihydrorhodamine 123 and nitration of tyrosine and were found to be effective in
      attenuating these reactions. The tetramer was particularly efficient at
      protecting against oxidation and nitration reactions. Epicatechin oligomers found
      in cocoa powder and chocolate may be a potent dietary source for defense against
      peroxynitrite.

PMID- 10917930
TI  - Effects of cocoa extracts on endothelium-dependent relaxation.
AB  - The aim of this study was to examine the effects of procyanidins derived from
      cocoa on vascular smooth muscle. Two hypotheses were tested: 1) extracts of
      cocoa, which are rich in procyanidins, cause endothelium-dependent relaxation
      (EDR), and 2) extracts of cocoa activate endothelial nitric oxide synthase (NOS).
      The experiments were carried out on aortic rings obtained from New Zealand White
      rabbits. The polymeric procyanidins (tetramer through decamer of catechin) caused
      an EDR. In addition, the Ca(2+)-dependent NOS activity, measured by the L
      arginine to L-citrulline conversion assay, was significantly increased in aortic
      endothelial cells exposed to polymeric procyanidins, whereas monomeric compounds
      had no such effect. These findings demonstrate that polymeric procyanidins cause
      an EDR that is mediated by activation of NOS.

PMID- 10917931
TI  - Epicatechin in human plasma: in vivo determination and effect of chocolate
      consumption on plasma oxidation status.
AB  - Diets that are rich in plant foods have been associated with a decreased risk for
      specific disease processes and certain chronic diseases. In addition to essential
      macronutrients and micronutrients, the flavonoids in a variety of plant foods may
      have health-enhancing properties. Chocolate is a food that is known to be rich in
      the flavan-3-ol epicatechin and procyanidin oligomers. However, the
      bioavailability and the biological effects of the chocolate flavonoids are poorly
      understood. To begin to address these issues, we developed a method based on HPLC
      coupled with electrochemical (coulometric) detection to determine the
      physiological levels of epicatechin, catechin and epicatechin dimers. This method
      allows for the determination of 20 pg (69 fmol) of epicatechin, which translates
      to plasma concentrations as low as 1 nmol/L. We next evaluated the absorption of
      epicatechin, from an 80-g semisweet chocolate (procyanidin-rich chocolate) bolus.
      By 2 h after ingestion, there was a 12-fold increase in plasma epicatechin, from
      22 to 257 nmol/L (P < 0.01). Consistent with the antioxidant properties of
      epicatechin, within the same 2-h period, there was a significant increase of 31%
      in plasma total antioxidant capacity (P < 0.04) and a decrease of 40% in plasma 2
      thiobarbituric acid reactive substances (P < 0.01). Plasma epicatechin and plasma
      antioxidant capacity approached baseline values by 6 h after ingestion. These
      results show that it is possible to determine basal levels of epicatechin in
      plasma. The data support the concept that the consumption of chocolate can result
      in significant increases in plasma epicatechin concentrations and decreases in
      plasma baseline oxidation products.

PMID- 10917932
TI  - A dose-response effect from chocolate consumption on plasma epicatechin and
      oxidative damage.
AB  - Evidence from epidemiological studies suggests that a diet high in plant foods
      and rich in polyphenols is inversely associated with a risk for cardiovascular
      and other chronic diseases. Chocolate, like red wine and green tea, is a
      polyphenol-rich food, primarily containing procyanidin polyphenols. These
      polyphenols are hypothesized to provide cardioprotective effects due to their
      ability to scavenge free radicals and inhibit lipid oxidation. Herein, we
      demonstrate that 2 h after the ingestion of a procyanidin-rich chocolate
      containing 5.3 mg total procyanidin/g, of which 1.3 mg/g was (-)-epicatechin
      (epicatechin), plasma levels of epicatechin increased 133 +/- 27, 258 +/- 29 and
      355 +/- 49 nmol/L in individuals who consumed 27, 53 and 80 g of chocolate,
      respectively. That the rise in plasma epicatechin levels was functionally
      significant is suggested by observations of trends for dose-response increases in
      the plasma antioxidant capacity and decreases in plasma lipid oxidation products.
      The above data support the theories that in healthy adults, 1) a positive
      relationship exists between procyanidin consumption and plasma procyanidin
      concentration and 2) the rise in plasma epicatechin contributes to the ability of
      plasma to scavenge free radicals and to inhibit lipid peroxidation.

PMID- 10917933
TI  - Cocoa and wine polyphenols modulate platelet activation and function.
AB  - There is speculation that dietary polyphenols can provide cardioprotective
      effects due to direct antioxidant or antithrombotic mechanisms. We report in
      vitro and postingestion ex vivo effects of cocoa procyanidins, a procyanidin-rich
      cocoa beverage and dealcoholized red wine (DRW) on human platelet activation. In
      a series of in vitro studies, cocoa procyanidin trimers, pentamers or DRW (3 and
      10 micromol/L) were incubated with citrated peripheral whole blood in the
      presence and absence of platelet agonists. Platelet activation was detected using
      fluorescent-labeled monoclonal antibodies recognizing the fibrinogen binding
      conformation of GPIIb-IIIa (referred to herein as PAC-1 binding) and the
      activation-dependent platelet epitope CD62P (P-selectin). The percentage of CD42a
      positive platelets coexpressing PAC-1 binding and/or CD62P was determined by
      multiparameter flow cytometry. Procyanidin trimers, pentamers and DRW added to
      whole blood in vitro increased PAC-1 binding and P-selectin expression. In
      contrast, procyanidin trimers, pentamers and DRW inhibited the platelet
      activation in response to epinephrine. The effects on platelet activation of
      cocoa beverage and DRW consumption were also studied in healthy subjects.
      Citrated blood was obtained before and 2 and 6 h after the ingestion of a cocoa
      beverage, a caffeine-containing beverage, DRW or water. Platelet activation was
      measured by flow cytometry. The consumption of DRW did not affect the expression
      of activation-dependent platelet antigens, either unstimulated or after ex vivo
      activation with epinephrine. However, the consumption of DRW increased PAC-1
      binding in response to 100 micromol/L ADP ex vivo. Cocoa consumption reduced
      platelet response to agonists ex vivo. The ingestion of water had no effect on
      platelet activation, whereas a caffeine-containing beverage augmented the
      response of platelets to epinephrine. In summary, select cocoa procyanidins and
      DRW added to whole blood in vitro increased expression of platelet activation
      markers in unstimulated platelets but suppressed the platelet activation response
      to epinephrine. In contrast, cocoa consumption suppressed unstimulated and
      stimulated platelet activation in whole blood. This suppressive effect observed
      on platelet reactivity may explain in part the reported cardioprotective effects
      of dietary polyphenols.

PMID- 10917935
TI  - Subclavian flap angioplasty: does the arch look after itself?
AB  - OBJECTIVES: We sought to assess the early and long-term results of subclavian
      flap angioplasty in neonates and infants, with particular attention to growth of
      the hypoplastic arch. METHODS: A retrospective analysis of 185 consecutive
      patients who underwent subclavian flap angioplasty between 1974 and 1998 was
      carried out. The patients included 125 neonates and 60 infants, with a median age
      of 18 days. Sixty-six (36%) patients had an additional ventricular septal defect,
      41 (22%) patients had aortic arch hypoplasia diagnosed preoperatively, 141 (76%)
      had an associated patent ductus arteriosus, and 41 (22%) had additional complex
      heart disease. Follow-up was with transthoracic Doppler echocardiography in all
      patients. RESULTS: The early mortality was 3%. Recoarctation, defined as a
      Doppler gradient of 25 mm Hg or more, occurred in 11 (6%) patients at a median
      follow-up of 6.2 years (6.2 +/- 4.6 years). This included 4 of the 41 patients in
      whom arch hypoplasia was diagnosed preoperatively. There were no complications
      with the left arm. By multivariate analysis, risk factors for death were
      determined to be residual arch hypoplasia and low birth weight. The only risk
      factor for recoarctation was persistent arch hypoplasia after surgical treatment.
      However, angiographic imaging of the aorta showed that recoarctation was not due
      to a hypoplastic transverse arch, and it was probably at the site of ductal
      tissue. Survival at 5 and 10 years was 98% and 96%, respectively. Freedom from
      reoperation for recoarctation at 2 years was 95%, and at 5, 10, and 15 years, it
      was 92%. CONCLUSIONS: Subclavian flap repair remains an effective technique for
      repair of aortic coarctation with excellent results and low mortality. In the
      majority of patients, arch hypoplasia regresses after this procedure.

PMID- 10917934
TI  - Twenty-five-year experience with rastelli repair for transposition of the great
      arteries.
AB  - OBJECTIVE: Our purpose was to describe the outcome of the Rastelli repair in D 
      transposition of the great arteries and to determine the risk factors associated
      with unfavorable events. METHODS: From March 1973 to April 1998, 101 patients
      with D -transposition of the great arteries and ventricular septal defect
      underwent a Rastelli type of repair. Median age and weight were 3.1 years (10th
      to 90th percentiles 0.3-9.9 years) and 12.8 kg (5.9-28.2). Pulmonary stenosis was
      present in 73 patients and pulmonary atresia in 18; 10 patients had no left
      ventricular outflow tract obstruction. RESULTS: There were 7 early deaths (7%)
      and no operative deaths in the last 7 years of the study. Risk factors for early
      death, by univariable analysis, included straddling tricuspid valve (P =.04) and
      longer aortic crossclamping times (P =.04). At a median follow-up of 8.5 years,
      there were 17 late deaths and 1 patient had undergone heart transplantation.
      Forty-four patients had reoperations for conduit stenosis, 11 for left
      ventricular outflow tract obstruction, and 28 had interventional catheterization
      to relieve conduit stenosis. Nine patients had late arrhythmias, and there were 5
      sudden deaths. Overall freedom from death or transplantation (Kaplan-Meier) was
      82%, 80%, 68%, and 52% at 5, 10, 15, and 20 years, respectively. Freedom from
      death or reintervention (catheterization or surgical treatment) was 53%, 24%, and
      21% at 5, 10, and 15 years of follow-up, respectively. CONCLUSIONS: The Rastelli
      repair can be performed with low early mortality. However, substantial late
      morbidity and mortality are associated with conduit obstruction, left ventricular
      outflow tract obstruction, and arrhythmia.

PMID- 10917936
TI  - Sialyl lewis oligosaccharide preserves cardiopulmonary and endothelial function
      after hypothermic circulatory arrest in lambs.
AB  - OBJECTIVE: Neutrophil adhesion to endothelium contributes to cardiopulmonary
      dysfunction after cardiac surgical procedures. Initial neutrophil-endothelial
      interactions involve selectins, which bind carbohydrate ligands, such as sialyl
      Lewis(X). Blockade of selectin-mediated neutrophil interactions with CY1503, a
      synthetic oligosaccharide analog of sialyl-Lewis(X), could limit neutrophil
      mediated injury after cardiopulmonary bypass. METHODS: The efficacy of CY1503
      treatment was tested in a lamb model of cardiopulmonary bypass with hypothermic
      circulatory arrest. Neonatal lambs received CY1503 (n = 6, CPB-CY1503) or saline
      solution vehicle (n = 7, CPB-saline) into the pump prime before bypass and as a
      continuous infusion throughout reperfusion. Five lambs served as control animals
      for in vitro microvessel studies. Indexes of myocardial function (preload
      recruitable stroke work index, and rate of pressure rise) and pulmonary function
      (compliance, airway resistance, and arterial PO (2)) were measured before bypass
      and during reperfusion. The effect of CY1503 on endothelium-dependent vascular
      reactivity was assessed by means of in vitro pulmonary and coronary microvessel
      studies. RESULTS: Myocardial function was depressed after circulatory arrest, but
      CY1503 preserved function near baseline (36% +/- 25% vs 99% +/- 19% of baseline
      at 3 hours of reperfusion). CY1503-treated animals also demonstrated improved
      pulmonary function during reperfusion. In vitro microvessel analysis of vascular
      reactivity revealed endothelial dysfunction after circulatory arrest compared
      with control lambs. CY1503-treated lambs (CPB-CY1503) had intact endothelial
      function, as demonstrated by normal vasodilatory responses to endothelium
      dependent vasodilators. CONCLUSIONS: CY1503 preserves cardiopulmonary and
      endothelial function after cardiopulmonary bypass and hypothermic circulatory
      arrest in neonatal lambs. This suggests a role for selectin-mediated, neutrophil
      endothelial interactions in the inflammatory response after cardiac operations.

PMID- 10917937
TI  - Cardiac performance after deep hypothermic circulatory arrest in chronically
      cyanotic neonatal lambs.
AB  - OBJECTIVES: It is controversial whether immature cyanotic hearts are more
      susceptible to ischemic injury than normoxemic hearts. Acutely induced alveolar
      hypoxic stress before cardiopulmonary bypass has been used as a model of cyanosis
      and is reported to worsen recovery of immature hearts after subsequent ischemic
      insult by means of a free radical injury mechanism. Because of concerns about the
      relevance of acute alveolar repair to the chronic cyanosis encountered
      clinically, we assessed the effects of chronic cyanosis without alveolar hypoxia,
      acute alveolar hypoxia, and normoxemia on recovery of cardiac function after deep
      hypothermic circulatory arrest. METHODS: A chronic cyanosis model was created in
      8 lambs by an anastomosis between the pulmonary artery and the left atrium
      (cyanosis group). Eight lambs underwent sham operation (control). One week later,
      the animals underwent cardiopulmonary bypass with 90 minutes of deep hypothermic
      circulatory arrest at 18 degrees C. Another 8 lambs underwent 45 minutes of
      hypoxic ventilation before bypass, with arterial oxygen tension being maintained
      at 30 mm Hg (acute hypoxia group). Cardiac index, preload recruitable stroke
      work, and tau were measured. Malondialdehyde and nitrate-nitrite, nitric oxide
      metabolites, were also measured in the coronary sinus. Myocardial antioxidant
      reserve capacity at 2 hours of reperfusion was assessed by measuring lipid
      peroxidation in left ventricular tissue samples incubated with t
      butylhydroperoxide at 37 degrees C. RESULTS: Oxygen tension was 35 +/- 3 mm Hg in
      the acute hypoxia group versus 93 +/- 7 mm Hg in the control group. In the acute
      hypoxia group the recovery of cardiac index, preload recruitable stroke work, and
      tau were significantly worse than that found in both the control and cyanosis
      groups. Preload recruitable stroke work at 2 hours of reperfusion was slightly
      but significantly lower in the cyanosis group than in the control group. The
      postischemic level of nitric oxide metabolites was significantly lower in the
      acute hypoxia group than in the cyanosis and control groups. However,
      malondialdehyde levels in the coronary sinus and myocardial antioxidant reserve
      capacity were not significantly different among the groups. CONCLUSION: Recovery
      of left ventricular function after deep hypothermic circulatory arrest in
      neonatal lambs with chronic cyanosis was slightly worse than that found in
      acyanotic animals. Acute hypoxia before bypass was associated with significantly
      worse recovery of left ventricular function, and the mechanism of injury may be
      related to an impairment of nitric oxide production. Free radical injury does not
      appear to explain any differences among cyanotic, acyanotic, and acutely hypoxic
      animals in recovery of left ventricular function after ischemia.

PMID- 10917938
TI  - Lamotrigine improves cerebral outcome after hypothermic circulatory arrest: a
      study in a chronic porcine model.
AB  - BACKGROUND: Glutamate excitotoxicity has an important role in the development of
      brain injury after prolonged hypothermic circulatory arrest. The goal of the
      present studies was to determine the potential efficacy of lamotrigine, an Na(+)
      channel blocker, to mitigate cerebral injury after hypothermic circulatory
      arrest. METHODS: Sixteen pigs (21-27 kg) were randomly assigned to receive
      lamotrigine (20 mg/kg) or placebo in a blinded fashion before a 75-minute period
      of hypothermic circulatory arrest (20 degrees C). Hemodynamic,
      electroencephalographic, and metabolic monitoring were carried out. S-100beta
      protein was determined up to the first postoperative morning. Daily behavioral
      assessment was performed until the animal died or was put to death on day 7.
      Histologic analysis of the brain was carried out in all animals. RESULTS:
      Complete behavioral recovery was seen in 5 of 8 (63%) animals after lamotrigine
      administration, compared with 1 of 8 (13%) in the placebo group (P =.02). Among
      the animals that survived for 7 days, the median behavioral score was higher in
      the lamotrigine group (8 vs 7, P =.02). The medians of recovered
      electroencephalographic bursts in the lamotrigine group were higher than those in
      the placebo group 4 1/2 hours after the start of rewarming (P =.01). The median S
      100beta level was lower in the lamotrigine group (0.01 microg/L) than in placebo
      controls (0.1 microg/L) 20 hours after the start of rewarming (P =.01). The
      median of total histopathologic score was 5.5 in the lamotrigine group and 7.5 in
      the placebo group (P =.06). CONCLUSIONS: The present data suggest that
      lamotrigine improves neurologic outcome after a prolonged period of hypothermic
      circulatory arrest.

PMID- 10917939
TI  - Interleukin 6 induction in the canine myocardium after cardiopulmonary bypass.
AB  - OBJECTIVE: Interleukin 6 is a proinflammatory cytokine with a plasma
      concentration that has been noted to increase in response to cardiopulmonary
      bypass. The source of interleukin 6 after cardiopulmonary bypass is unknown. This
      study examined the myocardium as a potential source of interleukin 6 in this
      context. METHODS: Dogs underwent 90 minutes of hypothermic cardiopulmonary bypass
      with 60 minutes of cardioplegic arrest. After rewarming, they were reperfused
      with the chest open for either 3 (n = 4) or 6 (n = 4) hours, at the end of which
      myocardial samples were obtained. Four additional animals undergoing open
      thoracotomy without bypass served as time-matched controls. Northern blot
      analysis, reverse transcriptase-polymerase chain reaction, and in situ
      hybridization were used to examine the myocardium for the induction of
      interleukin 6 and intercellular adhesion molecule-1. RESULTS: Northern blot
      analysis and reverse transcriptase-polymerase chain reaction demonstrated a
      marked increase in myocardial interleukin 6 messenger RNA in 3 of 4 dogs at 3
      hours after bypass and 3 of 4 dogs at 6 hours after bypass, which was not present
      in sham-bypass control animals. Northern blots at 3 hours after cardiopulmonary
      bypass also demonstrated myocardial intercellular adhesion molecule-1 induction.
      In situ hybridization studies confirmed that cardiac myocytes were a principal
      source of interleukin 6 messenger RNA early after cardiopulmonary bypass.
      Northern blots of messenger RNA extracted from isolated neutrophils and
      mononuclear leukocytes obtained from blood samples before bypass, at the end of
      bypass, and 3 hours after bypass failed to demonstrate interleukin 6 induction.
      CONCLUSION: Despite protection with cold cardioplegic arrest, the myocardium was
      a significant source of interleukin 6 synthesis after cardiopulmonary bypass.
      Local production of interleukin 6 may play a pivotal role in postoperative
      myocardial function.

PMID- 10917940
TI  - An entrustment model of consent for surgical treatment of life-threatening
      illness: perspective of patients requiring esophagectomy.
AB  - OBJECTIVE: Consent to treatment has been extensively discussed and prescribed
      from the viewpoint of law, ethics, and policy experts; the viewpoint of patients
      is less well represented. The purpose of this study was to describe the process
      of decision making and consent to surgical treatment from the patients'
      perspective, in the context of life-threatening illness. METHODS: Face-to-face
      interviews with 36 patients who had recovered from esophagectomy for cancer at
      university hospitals in Toronto, Ontario, were analyzed by means of a qualitative
      analytic approach. RESULTS: Instead of the accepted model of informed consent and
      shared decision making, patients identified 6 concepts that describe their
      experience: (1) cultural belief in surgical cure, (2) enhancement of trust
      through the referral process, (3) idealization of the specialist surgeon, (4)
      belief in expertise rather than medical information, (5) resignation to risks of
      treatment, and (6) acceptance of an expert recommendation as consent to
      treatment. These concepts were developed into a model of entrustment that unites
      the narratives of all our patients. CONCLUSIONS: There is a gap between accepted
      legal and ethical theories concerning consent and the patients' account of their
      experiences with surgical treatment of esophageal cancer. Although our findings
      should not be used to circumvent the ethical and legal requirements of the
      consent process and are limited to survivors of treatment of life-threatening
      disease, they support a careful reassessment of informed consent that includes
      the perspective of patients.

PMID- 10917941
TI  - Open window thoracostomy followed by intrathoracic flap transposition in the
      treatment of empyema complicating pulmonary resection.
AB  - OBJECTIVE: Successful treatment of postoperative empyema remains a challenge for
      thoracic surgeons. We report herein our 12-year experience in the management of
      this condition by means of open window thoracostomy. METHODS: Open window
      thoracostomy was used in the treatment of 46 patients with empyema complicating
      pulmonary resection. A bronchopleural fistula was associated in 39 of 46 cases.
      Previous operations included pneumonectomy (n = 30), bilobectomy (n = 5),
      lobectomy (n = 9), and wedge resection (n = 2) performed for benign (n = 10) or
      malignant (n = 36) disease. In 10 patients open window thoracostomy was
      definitive because of patient death (n = 2), concomitant major illness (n = 2),
      tumor recurrence (n = 4), spontaneous closure (n = 1), or patient choice (n = 1).
      In 36 cases intrathoracic flap transposition was eventually performed. Muscular
      (n = 29), omental (n = 5), or combined muscular and omental (n = 2) flaps were
      used to obliterate the thoracostomy cavity and to close a possibly associated
      bronchopleural fistula. In 9 patients with postpneumonectomy cavities too wide to
      be filled by the available flaps, a limited thoracoplasty represented an
      intermediate step. RESULTS: Among patients treated with definitive open window
      thoracostomy, local control of the infection was achieved in all the survivors
      (8/8). After open window thoracostomy and subsequent flap transposition, success
      (definitive closure of the thoracostomy and, if present, of the bronchopleural
      fistula) was achieved in 27 (75. 0%) of 36 patients. Four initial failures could
      be salvaged by means of reoperation (initial reopening of thoracostomy and
      subsequent muscular or omental transposition). CONCLUSION: Open window
      thoracostomy followed by intrathoracic muscle or omental transposition represents
      a valid therapeutic option in patients with empyema complicating pulmonary
      resections.

PMID- 10917943
TI  - Surgical strategy for severe tricuspid valve regurgitation complicated by
      advanced mitral valve disease: long-term outcome of tricuspid valve supra-annular
      implantation in eighty-eight cases.
AB  - OBJECTIVE: Although annuloplasty has been the most commonly performed surgical
      modality for severe tricuspid regurgitation, tricuspid valve supra-annular
      implantation has been performed in our hospital for more than a decade. The aim
      of this study was to assess the long-term outcome of tricuspid valve supra
      annular implantation in a subgroup of patients with severe tricuspid
      regurgitation, those who also had advanced mitral valve disease. METHODS: Mitral
      valve replacement in conjunction with tricuspid valve supra-annular implantation
      was performed on 88 patients at our hospital between 1984 and 1998. The patients
      (mean age 57 +/- 11 years) were followed up for an average of 7.2 +/- 4.5 years
      after the operation (range 0-14 years); total follow-up was 643.1 patient-years.
      All patients except 2 (97.6%) were included in the follow-up. We evaluated the
      mortality, the cause of death, survival, the freedom from structural valve
      deterioration and reoperation, postoperative complications, and long-term
      echocardiographic findings. RESULTS: Overall survival at 14 years was 69% +/-
      7.7%. Freedom from structural valve deterioration at 14 years was 100% and from
      reoperation, 88% +/- 9. 4%. There were no instances of pulmonary thromboembolism
      or of complications associated with fatal arrhythmias. Echocardiography showed
      little residual tricuspid regurgitation, no atrophic and stenotic change in the
      native tricuspid valve, and no thrombus formation between native valve and the
      implanted bioprosthesis. CONCLUSIONS: The procedure's simplicity, the good long
      term durability of the bioprosthesis, and the absence of fatal arrhythmias and
      pulmonary thromboembolism indicate that tricuspid valve supra-annular
      implantation is a useful procedure for patients with severe tricuspid
      regurgitation complicated by advanced mitral valve disease.

PMID- 10917942
TI  - Needlescopic surgery for palmar hyperhidrosis.
AB  - OBJECTIVE: The aim of this study was to develop a less invasive technique for
      video-assisted thoracic sympathectomy. METHODS: A newly designed trocar was used.
      A skin incision of 2.0 to 2.5 mm in length was made in the third or fourth
      intercostal space at the midaxillary line. After insertion of the trocar,
      thoracic sympathectomy with electrocautery was carried out at the level of the
      second and third ribs. RESULTS: From October 1998 to March 1999, 180 patients
      with palmar hyperhidrosis underwent this technique. No complications related to
      the technique occurred, and within 1 week the operative wound had almost
      completely disappeared. There were recurrences necessitating reapplication of the
      technique. CONCLUSION: The technique allowed healing without a scar and improved
      the patient's cosmesis.

PMID- 10917944
TI  - The in vitro hydrodynamic characteristics of the porcine pulmonary valve and root
      with regard to the ross procedure.
AB  - OBJECTIVE: The hydrodynamic parameters and leaflet motion of the porcine
      pulmonary root and valve and the performance of the pulmonary autograft implanted
      in subcoronary position or as a free-standing root were investigated at systemic
      and pulmonary pressures in vitro. METHODS: Ten fresh pulmonary and aortic roots
      (anulus diameter, 20-25 mm) were tested in a pulsatile flow simulator. Five free
      sewn pulmonary valves were implanted in aortic roots in the subcoronary position,
      and 5 pulmonary roots were implanted as free-standing roots. The external
      diameter of the roots was measured at the sinotubular junction in a pressure
      range of 0 to 120 mm Hg. The transvalvular gradient and regurgitation were
      measured, and the effective orifice area was calculated. The leaflet motion was
      recorded on video tape. RESULTS: The fresh pulmonary roots were more compliant
      than their aortic counterparts (33% +/- 3. 0% vs 7% +/- 1.5% with dilatation at 0
      30 mm Hg and 46% +/- 8.4% vs 35% +/- 7.8% with dilatation at 0-120 mm Hg). The
      pulmonary roots had a lower pressure drop at systemic than at pulmonary
      pressures. The pressure drops of the pulmonary roots were also lower than those
      of the aortic roots in the systemic pressure range. The leaflet opening of the
      pulmonary valve was triangular, with low bending deformation at all pressures.
      Implanting the free-sewn pulmonary valve in the subcoronary position or the
      pulmonary root as a free-standing root did not affect the hydrodynamic parameters
      and leaflet motion adversely. CONCLUSION: The pulmonary valve and root could
      easily withstand aortic pressures in vitro. A biphasic dilatation curve ensures
      that higher pressures did not overdilate the pulmonary root. Moreover, valve
      performance was better at systemic pressures.

PMID- 10917945
TI  - Bilateral skeletonized internal thoracic artery grafting in 303 patients seventy
      years and older.
AB  - OBJECTIVES: Higher patency rates of the internal thoracic artery have led
      myocardial revascularization with bilateral internal thoracic arteries to be a
      procedure designated primarily for young patients. Fewer leg wound complications
      and sternal collateral flow preservation with the skeletonizing dissection
      technique can make bilateral internal thoracic artery grafting attractive also
      for elderly patients. METHODS: Between May 1996 and May 1998, 303 consecutive
      patients aged 70 years or older (mean age 75.5 years; range 70-92 years)
      underwent coronary artery bypass grafting with double skeletonized internal
      thoracic arteries. Forty-four (14.5%) patients were 80 years or older, and 89
      (28%) had diabetes. The mean number of grafts was 3.1 per patient (2-6). RESULTS:
      Operative mortality was 2.6% (n = 8): it was higher for octogenarians (6.8%) than
      for younger patients (1.9%) (P =.06). The only significant preoperative
      predictors of early mortality were complicated percutaneous transluminal coronary
      angioplasty (P =.03) and preoperative use of intra-aortic balloon pumping (P
      =.03). Six patients (2%) had sternal wound infections for which chronic lung
      disease (P =.02) and emergency operation (P =.006) were the only significant
      predictors. Twenty-two (7.2%) late deaths occurred, and 1- and 3-year survivals
      were 93% and 90%, respectively. The 3-year survival of patients 80 years old or
      older was 92%. CONCLUSIONS: Bilateral grafting of the skeletonized internal
      thoracic artery carries relatively low morbidity and mortality in elderly
      patients and can be recommended for selected patients including octogenarians.

PMID- 10917946
TI  - Midterm endothelial function and remodeling of radial artery grafts anastomosed
      to the aorta.
AB  - BACKGROUND: The purpose of this study was to elucidate the midterm endothelium
      dependent vasodilatory capacity of radial artery grafts anastomosed to the aorta,
      as well as their morphometric evolution with the time. METHODS: Five years after
      surgery we evaluated the response of aorta-anastomosed radial artery grafts to
      the endovascular infusion of acetylcholine in 11 of the first 61 patients
      operated on at our institution, and we compared it to the response with that of
      internal thoracic artery grafts. Moreover, the first 20 patients who had a
      perfect radial artery graft on angiography at 1 year were restudied at 5 years
      and subjected to a comparative analysis of the diameters of the radial artery
      graft and the grafted coronary arteries. RESULTS: At midterm angiography,
      dilation of the 2 types of grafts was similar in response to acetylcholine
      administration (radial artery, from 2.61 +/- 0.39 to 2. 90 +/- 0.34 mm; internal
      thoracic artery, from 2.68 +/- 0.21 to 2.93 +/- 0.27 mm; P =.01 for both). The
      diameters of aorta-anastomosed radial artery grafts and grafted coronary arteries
      increased between both 1 and 5 years according to angiographic studies (radial
      artery grafts, from 2.08 +/- 0.45 to 2.54 +/- 0.53 mm; grafted coronary arteries,
      from 1.92 +/- 0.47 to 2.18 +/- 0.41 mm; P <.001 for both), but the increase was
      greater for the radial artery grafts (P <.001). CONCLUSIONS: Aorta-anastomosed
      radial artery grafts maintain an appreciable capacity for endothelium-dependent
      vasodilatation 5 years after implantation and undergo a progressive increase in
      luminal diameter with time. These observations contradict the presumed tendency
      for progressive fibrous intimal hyperplasia to develop in radial artery grafts.

PMID- 10917947
TI  - Limitations of unidimensional indexes of right ventricular contractile function
      in conscious dogs.
AB  - OBJECTIVE: Our goal was to examine the validity of unidimensional indexes of
      right ventricular contractile performance in vivo. METHODS: Unidimensional
      indexes and global measurements of right ventricular volume and contractile
      performance were compared in 6 conscious dogs. Vena caval occlusions were
      performed before (control) and during pulmonary arterial or aortic constriction.
      RESULTS: Moderately strong relationships were demonstrated between right
      ventricular septal-free wall indexes and global measurements of right ventricular
      end-diastolic and end-systolic volumes, stroke volume, stroke work, and the slope
      of the preload recruitable stroke work relationship, respectively, under control
      conditions (mean r (2) range 0.69-0.94). These relationships were shifted
      significantly, however, by increased right ventricular afterload. Increased left
      ventricular afterload significantly shifted the relationships between right
      ventricular septal-free wall dimensions and end-diastolic and end-systolic
      volumes. Relationships between the corresponding regional right ventricular free
      wall segmental indexes and global measurements under control conditions were
      weaker (mean r (2) range 0.12-0.65) and were significantly more sensitive to
      distortion by both increased right and left ventricular afterload, the effects of
      which were generally in opposite directions. These observations are consistent
      with significant ventricular interactive effects on the relationship between
      single right ventricular dimensions and right ventricular volume. CONCLUSION:
      Unidimensional right ventricular measurements are not reliable surrogates for
      right ventricular volume when assessing right ventricular contractile performance
      in the intact heart.

PMID- 10917948
TI  - Functional integrity and aging of the left internal thoracic artery after
      coronary artery bypass surgery.
AB  - OBJECTIVE: To study the endothelial function in the left internal thoracic artery
      after coronary artery bypass surgery and to identify predictors of early
      dysfunction, we performed a provocative test with acetylcholine in 23 male
      patients who underwent routine postoperative coronary angiography. METHODS: The
      change in mean diameter of the proximal thoracic artery was assessed by
      quantitative angiography after selective injections of acetylcholine and
      nitroglycerin. RESULTS: The thoracic artery showed a 6.8% (P <. 001) and 9.0% (P
      <.001) increase in mean diameter after acetylcholine and nitroglycerin
      administration, respectively. Vasodilative responses to acetylcholine and
      nitroglycerin administration were strongly correlated (R: 0.88; P <.001). Among
      the common risk factors, only age was associated with an impairment in the
      vasodilative response of the arterial graft (P =.001), and acetylcholine-induced
      vasodilation was inversely correlated to the age of the patient (R: 0.69; P
      <.001). CONCLUSIONS: Endothelium-dependent vasodilative response to acetylcholine
      administration seems well preserved in the left internal thoracic artery after
      surgery. Common risk factors, except for age, do not affect the functional
      integrity of the arterial graft. The vasodilative properties of the graft depend
      on the age of the patient and do not deteriorate over time after operation.

PMID- 10917949
TI  - Neointimal formation at the sites of anastomosis of the internal thoracic artery
      grafts after coronary artery bypass grafting in human subjects: an
      immunohistochemical analysis.
AB  - OBJECTIVES: The aim of this study was to evaluate the cellular composition and
      cell proliferative activity of neointimal tissue in human internal thoracic
      artery grafts and to characterize the differentiation state of neointimal smooth
      muscle cells at early stages after coronary artery bypass grafting. METHODS: The
      anastomotic sites and body segments of 7 patent grafts were obtained at autopsy
      from 7 patients who died within 92 days after operation. Serial sections were
      examined by immunohistochemical techniques to identify macrophages, endothelial
      cells, smooth muscle cell phenotype, and proliferating cells. For the
      identification of the cell types that show cell proliferative activity,
      immunodouble staining was also performed. RESULTS: In all body segments the
      luminal surface was completely covered by endothelial cells, and no areas showed
      thrombus formation or neointimal proliferation after grafting. In contrast, in
      the anastomotic segments endothelial denudation and focal disruption of the
      internal elastic lamina with adherence of fibrin-platelet thrombus and
      infiltration of macrophages were observed in the earliest stage after grafting.
      At these sites of injury, early neointimal tissue response had occurred, and cell
      proliferative activity was detected in macrophages and dedifferentiated smooth
      muscle cells. During the evolution of neointimal thickening, redifferentiation of
      neointimal smooth muscle cells occurred associated with the decline in
      proliferative activity. CONCLUSIONS: These observations strongly support the
      concept that excessive neointimal proliferation, which may occur at the site of
      anastomosis because of extensive damage to the arterial wall, could be one of the
      possible causes of failure of the internal thoracic artery graft in human beings.

PMID- 10917950
TI  - Early percutaneous tracheostomy after median sternotomy.
AB  - OBJECTIVE: Tracheostomy offers significant advantages over endotracheal
      intubation in patients requiring long-term assisted ventilation. However, in
      patients who have undergone median sternotomy, it is believed that the danger of
      microbial contamination and consecutive infection of the sternal wound with
      microbes from the tracheostomy is high when conventional tracheostomy is
      performed. In contrast, percutaneous techniques are less likely to result in
      tracheostomy infection and thus bacterial contamination of neighboring
      structures. Nonetheless, to date there has been no prospective study confirming
      or disproving this assumption. Our study evaluated outcome after percutaneous
      tracheostomy in patients with a median sternotomy. METHODS: A total of 144
      cardiac surgical patients had elective percutaneous tracheostomy at the bedside
      until postoperative day 14, with 4 different techniques. Systematic microbiologic
      monitoring of the sternal and tracheal wounds was used. RESULTS: In 13 patients
      sternal wound infection was suspected, but was confirmed in only 4 (2.8%)
      patients who actually showed microbial contamination of the sternum. In 2 of
      these patients, the identified microbes were not identical to those cultured from
      the trachea. The other 2 patients had sternal and tracheal cultures positive for
      methicillin-resistant Staphylococcus aureus. Cross-contamination of the
      sternotomy with microbes from the patient's airways was therefore ruled out. No
      patient had clinical signs of tracheostomy infection. Likewise, there were no
      cases of mediastinitis. CONCLUSIONS: On the basis of our data, we conclude that
      cross-contamination of the sternal wound with microbes from the trachea is not a
      problem. Elective percutaneous tracheostomy is safe, even if performed during the
      first 14 days after median sternotomy.

PMID- 10917951
TI  - Use of alternative medicine by patients undergoing cardiac surgery.
AB  - OBJECTIVE: Complementary and alternative medicine may influence cardiac surgical
      care by inducing coagulopathies and interacting with perioperative medications.
      We evaluated the significance of complementary and alternative medicine use in an
      acutely ill cardiac surgical population and assessed the willingness of patients
      to reveal these activities to their physicians and surgeons. METHODS: A total of
      376 consecutive patients undergoing preoperative or postoperative cardiothoracic
      surgical evaluations at an urban academic medical center were approached to
      complete a survey regarding use and attitudes toward complementary and
      alternative medicine. All surveys were administered and collected between March
      and May 1998. RESULTS: Completion rate was 70% (n = 263). Respondents were
      predominantly male (72%), white (76%), and well educated (59%). The overall rate
      of complementary and alternative medicine use was 75%, but excluding prayer and
      vitamins, which are often not considered complementary and alternative medicine
      therapies, the rate was 44%. There was no correlation between the use of
      complementary and alternative medicine and the parameters of gender, age, race,
      or education level. Only 17% responded that they had discussed complementary and
      alternative medicine with their physicians, and 48% responded that they did not
      want to discuss the topic at all. CONCLUSIONS: Complementary and alternative
      medicine is used as frequently in patients undergoing cardiac surgery, as in the
      general population. Physicians and surgeons should be aware that patients have no
      inherent predisposition toward or against using complementary and alternative
      medicine, but that they are unlikely to volunteer their experience with it. The
      unwillingness of patients to discuss complementary and alternative medicine with
      physicians has serious implications for their safety, especially in acute care
      situations.

PMID- 10917952
TI  - Early effects of right ventricular volume overload on ventricular performance and
      beta-adrenergic signaling.
AB  - OBJECTIVE: Right ventricular dysfunction is a poorly understood but persistent
      clinical problem. This study was undertaken to evaluate ventricular performance
      and beta-adrenergic receptor signaling in a tricuspid regurgitation model of
      right ventricular overload. METHODS: Seventeen dogs were chronically instrumented
      with epicardial dimension transducers. By means of the shell-subtraction model,
      right ventricular pressure-volume relationships were evaluated in normal and
      right ventricular overload states. Right ventricular chamber performance was
      quantified by the stroke work at an end-diastolic volume relationship. RESULTS:
      Right ventricular volume overload caused a 28% +/- 11% and 31% +/- 9% decline in
      chamber performance acutely and at 1 week, respectively, whereas end-diastolic
      volume increased from 45 +/- 21 to 60 +/- 30 mL (P =. 019). beta-Adrenergic
      receptor signaling in myocardial samples was assessed, examining adenylyl cyclase
      and G-protein-coupled receptor kinase activity. Stimulated adenylyl cyclase
      activity significantly decreased, and G-protein-coupled receptor kinase activity
      significantly increased in both left and right ventricular samples caused by
      increased levels of beta-adrenergic receptor kinase 1. No change in beta
      adrenergic receptor density was seen at 1 week. CONCLUSIONS: Early right
      ventricular overload is associated with impaired right ventricular chamber
      contractility, dilation, and, importantly, a biventricular alteration of beta
      adrenergic receptor signaling.

PMID- 10917954
TI  - A simple electronic device for resolving paradoxic motion in video-assisted
      thoracoscopic procedures.

PMID- 10917953
TI  - Recombinant human complement C5a receptor antagonist reduces infarct size after
      surgical revascularization.
AB  - OBJECTIVES: This study tested the hypothesis that a recombinant human C5a
      antagonist, CGS 32359, attenuates neutrophil activation and reduces infarct size
      in a porcine model of surgical revascularization. METHODS: CGS 32359 (0.16-16
      micromol/L) dose-dependently inhibited superoxide production by human C5a
      activated porcine neutrophils (18 +/- 3.7 vs 1.6 +/- 0.5 nmol/5 min/5 x 10(6)
      neutrophils; P <.05) and reduced neutrophil adherence to coronary endothelium
      from 194 +/- 9 to 43 +/- 6 neutrophils/mm(2) (P <.05). The left anterior
      descending coronary artery was occluded for 50 minutes, after which saline
      solution (n = 8), mannitol-buffer vehicle (n = 9, 102 mg/kg bolus, 102 mg. kg(
      1). h(-1)), or CGS 32359 (CGS, n = 7, 60 mg/kg bolus, 60 mg. kg(-1). h(-1)) was
      infused. After ischemia, 1-hour arrest was achieved by means of multidose
      hypothermic (4 degrees C) blood cardioplegia, followed by 2.5 hours of off-bypass
      reperfusion. The ligature on the left anterior descending artery was released
      before the second infusion of cardioplegic solution. RESULTS: Area at risk was
      similar in all groups (saline solution, 27% +/- 2%; mannitol-buffer vehicle, 26%
      +/- 2%; CGS, 26% +/- 2% left ventricular mass). Infarct size (area necrosis/area
      at risk) was significantly reduced by CGS (18% +/- 6%, P <.05) versus saline
      solution (52% +/- 3%) and mannitol-buffer vehicle (60% +/- 4%). Postischemic
      systolic shortening (sonomicrometry) in the area at risk was significantly
      improved with CGS (0.8% +/- 0.9%) compared with saline solution (-3.7% +/- 1.1%)
      and mannitol-buffer vehicle (-6.4% +/- 1.0%). Myeloperoxidase activity from
      accumulated neutrophils was less in the ischemic zone of CGS (0.014 +/- 0.002
      U/100 mg tissue; P <.05) than mannitol-buffer vehicle (0.133 +/- 0.012 U/100 mg
      tissue). CONCLUSIONS: We conclude that the recombinant human C5a receptor
      antagonist CGS 32359 inhibits surgical ischemia-reperfusion injury after coronary
      occlusion.

PMID- 10917956
TI  - The antithrombotic effect of aprotinin: actions mediated via the
      proteaseactivated receptor 1.
AB  - BACKGROUND: Despite aprotinin being in widespread clinical use to prevent
      bleeding during cardiac surgery, there remains concern that such a powerful
      hemostatic agent may also be prothrombotic, particularly in relation to coronary
      vein graft occlusion. The major thrombin receptor on platelets, protease
      activated receptor 1 (PAR1) requires proteolytic cleavage to transmit activating
      signals. Here we have investigated the effect of aprotinin on thrombin-induced
      PAR1 activation of platelets. METHODS AND RESULTS: Proteolysis-dependent and 
      independent responses of washed platelets were studied in vitro. Platelet
      aggregation induced by trypsin was dependent on PAR1 (inhibited by the PAR1
      specific antagonist peptide, FLLRN) and was completely blocked by aprotinin at
      doses more than 100 KIU/mL. Aggregation in response to thrombin, 1 nmol/L, was
      predominantly mediated through PAR1 and was inhibited 42.6% to 86.6% (P <.05
      .001) by pharmacologic doses of aprotinin (50-160 KIU/mL). Aprotinin did not
      inhibit the nonproteolytic agonists collagen, epinephrine, adenosine diphosphate,
      or phorbol 12-myristate 13-acetate. Furthermore, blockade of the thrombin
      response by aprotinin did not prevent subsequent platelet aggregation through
      collagen or epinephrine. Experiments with intraplatelet Ca(2+) fluxes, which
      provided an earlier measure of platelet activation, placed the effect of
      aprotinin proximal to the PAR1 activation event. Since aprotinin did not inhibit
      platelet responses to the nonproteolytic PAR1 agonist peptide, SFLLRN, this
      implied that aprotinin acted by preventing PAR1 receptor cleavage by thrombin.
      CONCLUSIONS: Aprotinin inhibits thrombin-induced platelet activation by
      preventing proteolysis of the PAR1 receptor. These findings argue against
      aprotinin being prothrombotic and suggest instead that aprotinin may have
      significant antithrombotic effects.

PMID- 10917955
TI  - An anti-inflammatory property of aprotinin detected at the level of leukocyte
      extravasation.
AB  - BACKGROUND: Aprotinin is a serine protease inhibitor used extensively in cardiac
      operations to reduce postoperative bleeding. It has also been used in trials
      aimed at reducing the systemic inflammatory response to cardiopulmonary bypass.
      It remains unclear whether the anti-inflammatory action of aprotinin is related
      to its general ability to suppress leukocyte activation or whether aprotinin can
      exercise effects during the leukocyte-endothelial cell adhesion cascade. METHODS:
      We used intravital microscopy to study the 3 main stages of the adhesion cascade
      (leukocyte rolling, firm adhesion, and extravasation) within the mesenteric
      microcirculation of rats. This in vivo technique allows leukocyte recruitment to
      be viewed directly through the transparent mesentery of anesthetized animals.
      RESULTS: Aprotinin, given by continuous infusion at a clinically relevant dose,
      exerted no effect on the rolling or firm adhesion responses toward local
      chemoattractant N -formyl-methyl-leucyl-phenylalanine but significantly inhibited
      extravasation of leukocytes (73% at 40 minutes, P =.04) into surrounding tissues.
      In parallel in vitro experiments, aprotinin (used at 200, 800, and 1600 kIU/mL)
      dose dependently inhibited neutrophil transmigration through cultured endothelial
      cells in response to 3 different chemoattractants: N -formyl-methyl-leucyl
      phenylalanine (P <.001 at 800 and 1600 kIU/mL), interleukin 8 (P <.05 at 200
      kIU/mL and P <.001 at 800 and 1600 kIU/mL), and platelet-activating factor (P
      <.05 at 1600 kIU/mL). CONCLUSIONS: Our studies have therefore revealed a novel
      anti-inflammatory mechanism of aprotinin operating at the level of leukocyte
      extravasation. These findings may be relevant in the prevention of systemic
      inflammation after cardiopulmonary bypass through the use of protease inhibitors.

PMID- 10917957
TI  - Maximizing hemodynamic effectiveness of biventricular assistance by direct
      cardiac compression studied in ex vivo and in vivo canine models of acute heart
      failure.
AB  - OBJECTIVE: Direct cardiac compression improves effective ventricular
      contractility. However, associated reductions in filling volumes and increases in
      arterial pressure occurring at the onset of direct cardiac compression limit the
      degree to which cardiac output is augmented. We tested the hypothesis that active
      preload and afterload control maximizes the hemodynamic effectiveness of direct
      cardiac compression. METHODS AND RESULTS: Studies in isolated canine hearts
      loaded with a computer-controlled volume servo system that mimicked heart failure
      were used to clearly define the hemodynamic effects of direct cardiac
      compression. Immediately on initiation of direct cardiac compression, ventricular
      end-diastolic pressure and volume decreased substantially, arterial pressure
      increased, but stroke volume did not change significantly. When end-diastolic
      pressure was restored to about 20 mm Hg, stroke volume doubled; decreasing
      afterload resistance further increased stroke volume by about 30%. Such load
      adjustments were then tested in vivo in a canine model of acute heart failure
      induced by coronary artery microembolizations titrated to decrease cardiac output
      to 33% +/- 9% of control as end-diastolic pressure rose to 20.6 +/- 2.2 mm Hg.
      Direct cardiac compression decreased end-diastolic pressure to 11.4 +/- 2.6 mm Hg
      while increasing cardiac output from 0.8 +/- 0.2 to 1. 4 +/- 0.5 L/min (to only
      approximately 55% of normal). Restoring end-diastolic pressure to 19.6 +/- 2.2 mm
      Hg by infusions of saline solution increased cardiac output to 1.9 +/- 0.5 L/min.
      Afterload reduction (nitroprusside), while maintaining end-diastolic pressure at
      19.8 +/- 1.3 mm Hg, increased cardiac output to its baseline, 2.8 +/- 1.1 L/min.
      CONCLUSIONS: Direct cardiac compression significantly improves ventricular
      pumping capacity and can restore cardiac output to about 60% of normal in the
      setting of acute heart failure. When combined with active preload and afterload
      manipulations, direct cardiac compression can restore cardiac output to normal.

PMID- 10917959
TI  - Mechanical support with microaxial blood pumps for postcardiotomy left
      ventricular failure: can outcome be predicted?
AB  - OBJECTIVE: We sought to identify the indications of mechanical support in
      postcardiotomy left ventricular failure in patients who are unable to undergo
      transplantation. METHODS: From 1989 through 1997, 61 patients with postcardiotomy
      left ventricular failure beyond intra-aortic balloon pumping were assisted with
      the Hemopump cardiac assist system (Medtronic, Minneapolis, Minn). Their mean age
      was 64 +/- 8 years. Comorbidity was prevalent; 47% underwent cardiac massage
      before pump support, and evolving myocardial infarction was diagnosed in 43%
      before surgery. Multivariable logistic regression of data known at the moment of
      pump insertion was performed to identify the risk factors for mortality. RESULTS:
      Sixty-five percent of the patients were weaned from the device, but only 30% were
      discharged home. Cardiac index evolution during the first hours after pump
      insertion (P <.001) is the only independent predictor for possibility to wean
      from the device in the multivariable analysis. Acute renal failure is the only
      variable retained in the model for 90-day mortality. Device-related complications
      were far more frequent with the femoral (54%) than with the transthoracic (6%)
      cannula. Only 13% of the patients had bleeding complications. CONCLUSIONS: One
      third of the patients with postcardiotomy heart failure refractory to use of the
      intra-aortic balloon pump can be saved with the use of an endovascular axial flow
      pump. It is impossible to predict lethal outcome on preoperative data alone. The
      early hemodynamic response to support seems to be related to functional recovery
      of the heart and subsequent weaning from the device.

PMID- 10917958
TI  - Selective mitochondrial adenosine triphosphate-sensitive potassium channel
      activation is sufficient to precondition human myocardium.
AB  - OBJECTIVES: Recently, the mitochondrial adenosine triphosphate-sensitive
      potassium channel has been suggested to be the final common effector of
      myocardial preconditioning. The purpose of this study is to determine whether
      selective mitochondrial adenosine triphosphate-sensitive potassium channel
      activation alone can precondition human myocardium from an ischemia/reperfusion
      insult. METHODS: Isolated human right atrial trabeculae were placed in tissue
      baths, paced, and subjected to 30 minutes of normothermic hypoxia (ischemia)
      followed by 45 minutes of reoxygenation (reperfusion). Trabeculae were
      preconditioned with a selective mitochondrial adenosine triphosphate-sensitive
      potassium channel opener (diazoxide 30 micromol/L) or a nonselective purinergic
      agonist, adenosine (125 micromol/L), for 5 minutes (adenosine) followed by a 10
      minute washout period. Developed force at end reperfusion (mean +/- standard
      error) was compared with baseline, and tissue creatine kinase and adenosine
      triphosphate levels were measured after ischemia/reperfusion. RESULTS: Trabeculae
      subjected to ischemia/reperfusion exhibited 30% +/- 2% of baseline developed
      force, whereas trabeculae subjected to selective adenosine triphosphate-sensitive
      potassium channel opening (diazoxide) and nonselective purinergic agonist
      (adenosine) recovered to 55% +/- 7% and 46% +/- 3% of baseline developed force,
      respectively. Tissue creatine kinase activity was preserved in both the diazoxide
      and adenosine-treated trabeculae (5.4 +/- 12 and 5.4 +/- 14 micromol/L per gram
      wet tissue) compared with ischemia/reperfusion (1.8 +/- 0.2 U/mg wet tissue).
      Adenosine triphosphate levels at end reperfusion were also increased in the
      trabeculae treated with selective (diazoxide) and nonselective (adenosine)
      adenosine triphosphate-sensitive potassium channel opener (4.1 +/- 0.01 and 4. 4
      +/- 0.2 micromol/L per gram wet tissue) compared with trabeculae subjected to
      ischemia/reperfusion (1.5 +/- 0.1 micromol/L per gram wet tissue). CONCLUSIONS:
      These results suggest that selective mitochondrial adenosine triphosphate
      sensitive potassium channel activation preconditions human myocardium and the
      protection conferred is equal to that of adenosine preconditioning. Targeted
      openers of mitochondrial adenosine triphosphate- sensitive potassium channels
      promote constructive protection of myocellular energy levels, contractile
      function, and cellular viability in human myocardium after ischemia/reperfusion.

PMID- 10917961
TI  - An improved method for topical cerebral cooling during deep hypothermic
      circulatory arrest.

PMID- 10917960
TI  - Vasopressin for refractory hypotension during cardiopulmonary bypass.

PMID- 10917962
TI  - Fatal intraoperative dissection of the innominate artery due to perfusion through
      the right axillary artery.

PMID- 10917963
TI  - New operative method for acute type B dissection: left carotid artery-left
      subclavian artery bypass combined with endovascular stent-graft implantation.

PMID- 10917964
TI  - Anatomic and physiologic correction of the restricted posterior mitral leaflet
      motion in chronic ischemic mitral regurgitation.

PMID- 10917965
TI  - A novel test of the surgical margin in patients with lung cancer undergoing
      limited surgery: lavage cytologic technique.

PMID- 10917966
TI  - Thoracoscopic major lung resection for primary lung cancer by a single surgeon
      with a voice-controlled robot and an instrument retraction system.

PMID- 10917967
TI  - Thoracic herniation of the transverse colon after transhiatal esophagectomy.

PMID- 10917968
TI  - Resection of lung cancer invading the diaphragm.

PMID- 10917969
TI  - Congenital horner syndrome: a rare though significant complication of subclavian
      flap aortoplasty.

PMID- 10917970
TI  - Cardiac blood-filled cyst at the atrialized portion of the right ventricle in a
      patient with ebstein anomaly: a case report.

PMID- 10917972
TI  - Cardiopulmonary bypass and severe drug intoxication

PMID- 10917971
TI  - Cardiopulmonary bypass and severe drug intoxication.

PMID- 10917973
TI  - Role for deep hypothermic circulatory arrest during repair of heart defects in
      infants.

PMID- 10917974
TI  - The use of diaphragmatic flaps in cardiac surgery.

PMID- 10917975
TI  - The use of diaphragmatic flaps in cardiac surgery

PMID- 10917977
TI  - C1 esterase inhibitor concentrate during surgery with cardiopulmonary bypass: is
      there an indication beyond substitution therapy in patients with hereditary
      angioneurotic edema?

PMID- 10917978
TI  - C1 esterase inhibitor concentrate during surgery with cardiopulmonary bypass: is
      there an indication beyond substitution therapy in patients with hereditary
      angioneurotic edema?

PMID- 10917976
TI  - Osteopontin expression and calcium content in human aortic valves.

PMID- 10917979
TI  - Cardiopulmonary bypass and heparin-induced thrombocytopenia: pitfalls of
      anticoagulation with danaparoid.

PMID- 10917980
TI  - Midline retroperitoneal versus midline transperitoneal approach for abdominal
      aortic aneurysm repair.
AB  - PURPOSE: The purpose of this study was to compare the midline retroperitoneal
      approach with the midline transperitoneal approach for abdominal aortic aneurysm
      (AAA) repair with respect to operative details, gastrointestinal complications,
      and wound complications. METHODS: From January 1990 through January 1998, 128
      patients underwent elective aortic reconstruction for infrarenal AAA. Of these,
      64 patients (the transperitoneal group) underwent conventional transperitoneal
      midline aortic exposure, whereas the remaining 64 patients (the retroperitoneal
      group) underwent retroperitoneal midline exposure of the aneurysm. RESULTS:
      Preclamp time, that is, the time from skin incision to aortic clamping, was
      significantly shorter in the transperitoneal group than in the retroperitoneal
      group (P <.001). However, the midline retroperitoneal approach was associated
      with decreased incidence of ileus (P <.01), earlier resumption of oral intake (P
      <.01), and decreased wound pain (P <.01), in comparison with the transperitoneal
      approach. Furthermore, there was no incidence of wound complications such as
      abdominal bulge or wound pain in any of the patients in the postoperative period
      or over the long term. CONCLUSIONS: The midline retroperitoneal approach for AAA
      was associated with fewer postoperative gastrointestinal and wound complications
      than the midline transperitoneal approach. Over the long term, there was no wound
      complication such as abdominal bulge and wound pain in any of the patients.

PMID- 10917981
TI  - Laparoscopic-assisted abdominal aortic aneurysmectomy.
AB  - PURPOSE: The technical elements and early results of laparoscopic-assisted
      abdominal aortic aneurysmectomy are described. METHODS: From February 1997 to May
      1999, 60 patients underwent elective laparoscopic surgery for infrarenal
      abdominal aortic aneurysm. Patients ranged in age from 53 to 87 years (mean age,
      70.6 years). The mean aneurysm size was 5.7 cm (range, 4.4-8.0 cm). All patients
      underwent aortography and computed tomography scanning preoperatively. Patients
      were not deemed candidates for the procedure when visceral arterial abnormalities
      requiring surgical treatment were present or an aortic aneurysm neck shorter than
      0.5 cm was found. A risk-stratification system was used as a means of
      quantitating risk factors and excluding high-risk patients. Aortic reconstruction
      was performed with retroperitoneal laparoscopy, with the patient in a modified
      right lateral decubitus position. An Endo TA 30 and an Endo TA 60 laparoscopic
      staplers (US Surgical, Norwalk, Conn) were used in occluding the common iliac
      arteries and aneurysm sac. Laparoscopic hemoclips were used as a means of
      occluding the lumbar arteries and other branches of the aneurysm sac. An
      aortobifemoral or aortobi-iliac bypass grafting procedure was performed by means
      of the laparoscope to position the graft and visualize the end-to-end aorta-to
      graft anastomosis, with distal anastomoses performed through counter incisions.
      RESULTS: Three patients died within 30 days of surgery (mortality rate, 5.0%).
      Complications included left ureteral injury (1), postoperative myocardial
      infarction (1), ileofemoral deep venous thrombosis (1), acute renal failure (2),
      colon ischemia (1), and infected graft limb requiring revision (1). The mean
      operative time was 7.7 hours, and the mean aortic cross-clamping time was 112
      minutes. Compared with a contemporary consecutive series of 100 patients
      undergoing open transabdominal or retroperitoneal aneurysmectomy performed by the
      same group of surgeons, the laparoscopic patients had decreased length of stays
      in the intensive care unit and the hospital, with less need for ventilator
      support, earlier resumption of a regular diet, and an earlier return to normal
      activity. At the follow-up examinations, all bypass grafts were patent.
      CONCLUSION: Laparoscopic-assisted aneurysmectomy is safe and effective and can be
      performed with good results. The longer operation time required is well tolerated
      in patients who are at good and moderate risk. Prior training in laparoscopic
      aortic surgery is necessary for surgeons to obtain the required level of
      expertise needed to perform these procedures. With these caveats, the results of
      our study suggest that laparoscopic-assisted aortic aneurysmectomy is appropriate
      for moderate-to-good risk (American Society of Anesthesiologists class of III or
      lower) operative candidates meeting standard criteria for aneurysm resection in
      whom preoperative computed tomography scan and biplane arteriography demonstrate
      a proximal aneurysm neck of 0.5 cm or larger and no need for visceral or internal
      iliac artery reconstruction. A randomized trial would be required to confirm the
      benefits of this procedure over open aneurysmectomy.

PMID- 10917982
TI  - Early inflammatory response after elective abdominal aortic aneurysm repair: a
      comparison between endovascular procedure and conventional surgery.
AB  - OBJECTIVE: To determine the nature of and to compare the inflammatory responses
      induced by (1) endovascular and (2) conventional abdominal aortic aneurysm (AAA)
      repair. MATERIAL AND METHODS: Twelve consecutive patients undergoing elective
      infrarenal AAA repair were prospectively studied. Seven patients were selected
      for endovascular procedures (the EAAA group); five patients underwent open
      surgery (the OAAA group). Three control patients undergoing carotid
      thromboendarterectomy were also included. Serial peripheral venous blood samples
      were collected preoperatively, immediately after declamping or placement of the
      endograft, and at hours 1, 3, 6, 12, 24, 48, and 72. Acute phase response
      expression of peripheral T lymphocyte and monocyte activation markers and
      adhesion molecules (flow cytometry), soluble levels of cell adhesion molecules
      (enzyme-linked immunosorbent assay), cytokine (tumor necrosis factor alpha,
      interleukin-6, and interleukin-8) release (enzyme-linked immunosorbent assay),
      and liberation of complement products (nephelometry) were measured. RESULTS:
      Regarding acute phase response, the EAAA and OAAA groups showed significant
      increases in C-reactive protein (P <.001 and P =.001), body temperature (P =.035
      and P =.048), and leukocyte count (P <.001 and P <.001). Similar time course
      patterns were observed with respect to body temperature (P =.372). Statistically
      significant different patterns were demonstrated for C-reactive protein (P =.032)
      and leukocyte count (P =.002). Regarding leukocyte activation, a significant
      upregulation of peripheral T lymphocyte CD38 expression was observed in the OAAA
      group only (P =.001). Analysis of markers such as CD69, CD40L, CD25, and CD54
      revealed no perioperative fluctuations in any group. Regarding circulating cell
      adhesion molecules, the EAAA and OAAA groups displayed significant increases in
      soluble intercellular adhesion molecule-1 (P =.003 and P =.001); there was no
      intergroup difference (P =.193). All groups demonstrated high soluble von
      Willebrand factor levels (P =.018, P =. 007, and P =.027), there being no
      differences in the patterns (P =. 772). Otherwise, soluble vascular cell adhesion
      molecule-1, soluble E-selectin, and soluble P-selectin did not appear to vary in
      any group. Regarding cytokine release, although a tendency toward high tumor
      necrosis factor alpha and interleukin-8 levels was noticed in the EAAA group,
      global time course effects failed to reach statistical significance (P =.543 and
      P =.080). In contrast, interleukin-6 showed elevations in all groups (P =.058, P
      <.001, and P =.004). Time course patterns did not differ between the EAAA and
      OAAA groups (P =.840). Regarding complement activation, the C3d/C3 ratio
      disclosed significant postoperative elevations in the EAAA and OAAA groups (P
      =.013 and P =.009). This complement product release was reduced in the EAAA group
      (P <.001). CONCLUSIONS: The current study indicated that both endovascular and
      coventional AAA repair induced significant inflammatory responses. Our findings
      showed that there were no large differences between the procedures with respect
      to circulating cell adhesion molecule and cytokine release. Moreover, the
      endoluminal approach produced a limited response in terms of acute phase
      reaction, T lymphocyte activation, and complement product liberation. This might
      support the concept that endovascular AAA repair represents an attractive
      alternative to open surgery. Given the relatively small sample size, further
      larger studies are required for confirmation of our observations.

PMID- 10917983
TI  - The cost-effectiveness of repairing ruptured abdominal aortic aneurysms.
AB  - BACKGROUND: Although advances in technology have reduced the operative risk of
      elective abdominal aortic aneurysm (AAA) repair, the surgical repair of ruptured
      AAAs is associated with a much poorer prognosis and a higher cost. Accordingly,
      it has been suggested that patients with predictably high rates of morbidity and
      mortality from ruptured AAA may not benefit from surgical intervention. METHODS
      AND RESULTS: A cost-effectiveness analysis was performed with the use of a Markov
      decision-analytic model to compute long-term survival in quality-adjusted life
      years and lifetime costs for a hypothetical cohort of patients with ruptured AAAs
      managed with either a strategy of open surgical repair or no intervention.
      Probability estimates for the various outcomes were based on a review of the
      literature. Average costs of (1) the immediate hospitalization ($28,356) and (2)
      complications resulting from the procedure were based on the average use of
      resources as reported in the literature and from a hospital's cost accounting
      system. Our measure of outcome was the incremental cost-effectiveness ratio. For
      our base-case analysis, the repair of ruptured AAAs was cost-effective with an
      incremental cost-effectiveness ratio of $10,754. (Society is usually willing to
      pay for interventions with cost-effectiveness ratios of less than $60,000; for
      example, the costeffectiveness ratios for coronary artery bypass grafting and
      dialysis are $9500 and $54,400, respectively.) In sensitivity analyses, the cost
      effectiveness of repairing ruptured AAAs was influenced only by alterations in
      the operative mortality. If the operative mortality exceeded 88%, repair of
      ruptured AAAs was no longer cost-effective. As an independent variable,
      increasing age had no substantial impact on the cost-effectiveness, although it
      is reported to be associated with increased operative mortality. It was necessary
      that the patient's cost of the initial hospitalization for ruptured AAA exceed
      $195,000 before repairing ruptured AAAs was no longer cost-effective.
      CONCLUSIONS: Our analysis suggests that despite the high cost and poor outcomes,
      the surgical repair of ruptured AAAs is still cost-effective when compared with
      no intervention. The cost of repairing ruptured AAAs falls within society's
      acceptable limits and therefore should not be a consideration in the management
      of patients with AAAs.

PMID- 10917984
TI  - The influence of gender on outcome after ruptured abdominal aortic aneurysm.
AB  - BACKGROUND: The influence of gender on the management of coronary artery disease
      is well documented, but few reports exist regarding the influence of gender on
      the management of peripheral arterial disease. OBJECTIVE: The purpose of this
      study was to examine the influence of gender on selection for and short-term and
      long-term outcomes of repair of ruptured abdominal aortic aneurysm (RAAA) in a
      regional vascular surgery unit. METHODS: Analysis of the prospectively gathered
      Lothian Surgical Audit database identified 692 patients (542 male and 150 female)
      admitted with RAAA between January 1, 1983, and December 31, 1995. Case notes
      were reviewed for patients who were admitted but not operated on. Operative
      mortality was defined as death within the same hospital admission. Long-term
      survival data were obtained from the General Register Office (GRO1 records)
      through record linkage by the Information and Statistics Division of the National
      Health Service of Scotland. RESULTS: A total of 542 men (78%; median age, 72
      years; age range, 46-93 years) and 150 women (22%; median age, 74 years; age
      range, 55-93 years) were admitted with RAAA (P =.12; Mann-Whitney U test). There
      was no significant difference in perioperative mortality between men and women.
      Although women who were not operated on (median age, 81 years; age range, 68-93
      years) were significantly (P =.005) older than men who were not operated on
      (median age, 77 years; age range, 54-93 years), for any given age group, women
      appeared less likely than men to be offered surgical repair. Long-term survival
      after successful repair was comparable for the genders. CONCLUSIONS: Gender has
      no influence on either short-term or long-term outcome for patients undergoing
      operative repair of RAAA. However, women are less likely to be selected for
      operation than their male counterparts.

PMID- 10917985
TI  - Plasma platelet-activating factor acetylhydrolase deficiency is associated with
      atherosclerotic occlusive disease in japan.
AB  - PURPOSE: Plasma platelet-activating factor acetylhydrolase (PAF-AH) is known to
      catalyze platelet-activating factor, thereby inactivating its inflammatory
      function. Deficiency of this enzyme is caused by a missense (G(994)-->T) in exon
      9 of the plasma PAF-AH gene. In this study, we investigated a possible
      association of this mutation with the risk of atherosclerotic occlusive disease
      (AO) in Japanese patients. METHODS: We studied 104 patients with AO. The control
      group consisted of 114 subjects matched for age and sex. Plasma PAF-AH activity
      was measured in the patients with AO. RESULTS: The prevalence of the mutant
      genotype (GT + TT ) was significantly more frequent in patients with AO than in
      control subjects (36.5% vs 23.7%; P <.05). Among the patients with AO, those with
      the mutant allele had significantly more risk factors of prior stroke or ischemic
      heart disease than patients with normal genotypes. Plasma PAF-AH activity was
      higher in patients with AO than in control subjects in normal genotype subgroups.
      CONCLUSIONS: The missense (G(994)-->T) in exon 9 of the plasma PAF-AH gene is
      associated with AO in Japanese people.

PMID- 10917986
TI  - A comparative evaluation of polytetrafluoroethylene, umbilical vein, and
      saphenous vein bypass grafts for femoral-popliteal above-knee revascularization:
      a prospective randomized Department of Veterans Affairs cooperative study.
AB  - PURPOSE: Currently, the choice of a vascular prosthesis for a femoral-popliteal
      above-knee arterial bypass graft is left to the surgeon's preference, because the
      available information on comparative evaluations is inconclusive. The Department
      of Veterans Affairs (VA) Cooperative Study 141 was established to identify
      whether improved patency exists with different bypass graft materials for
      patients with femoral-popliteal above-knee bypass grafts. METHODS: Between June
      1983 and June 1988, 752 patients at 20 VA medical centers were randomized to
      receive either an externally supported polytetrafluoroethylene (PTFE; N = 265),
      human umbilical vein (HUV; N = 261), or saphenous vein (SV; N = 226) for an above
      knee femoral-popliteal bypass graft. The indication for the bypass grafting
      operation was limb salvage in 67.5% of the patients. Patients were observed every
      3 months for the first year and every 6 months thereafter. All patients were
      instructed to take aspirin (650 mg) daily for the duration of the study.Doppler
      derived ankle-brachial indices (ABIs) were determined preoperatively and serially
      postoperatively. A bypass graft was considered to be patent when the Doppler
      derived postoperative ABI remained significantly improved (more than 0.15 units
      higher than their preoperative value) and additional objective information, such
      as angiograms or operations, did not contradict these observations. Patency
      failure also included bypass grafts that were removed because of an infection or
      aneurysmal degeneration. Patency rates were compared by using the Kaplan-Meier
      life table analysis. RESULTS: The cumulative assisted primary patency rates were
      statistically similar among the different conduit types at 2 years (SV, 81%; HUV,
      70%; PTFE, 69%). After 5 years, above-knee SV bypass grafts had a significantly
      (P </=.01) better patency rate (73%) than HUV bypass grafts (53%), which had a
      significantly (P </=.01) better patency rate than PTFE bypass grafts (39%). Limb
      salvage was slightly worse with PTFE conduits. The number of bypass graft
      thromboses and major amputations within the first 30 days was highest in the HUV
      group. CONCLUSION: The overall results of this prospective randomized study
      suggest that the SV should be considered as the bypass graft of choice for
      femoral-popliteal above-knee reconstruction and that, when a prosthetic bypass
      graft is used, an HUV should also be considered as an alternative choice to PTFE.

PMID- 10917987
TI  - A prospective randomized trial comparing vein with polytetrafluoroethylene in
      above-knee femoropopliteal bypass grafting.
AB  - OBJECTIVE: Despite many clinical studies, there is still uncertainty as to
      whether venous material is superior to polytetrafluoroethylene for
      femoropopliteal reconstruction proximal to the knee joint. Supported by early
      satisfactory results with thin-walled, stretched polytetrafluoroethylene for
      suprageniculate bypass grafts, a prospectively randomized clinical trial was
      designed to evaluate the effectiveness of reversed saphenous vein in comparison
      with that of polytetrafluoroethylene in above-knee arterial reconstruction.
      METHODS: In a 3-year period, 151 above-knee femoropopliteal bypass graft
      operations were performed in 136 patients (77 male, 59 female). The indication
      for operation was severe claudication in 120 cases, rest pain in 20 cases, and
      ulceration in 11 cases. For the bypass graft, a reversed saphenous vein was used
      in each of 75 cases, and a polytetrafluoroethylene prosthesis was used in each of
      76 cases. Preoperative risk factors were diabetes (24%), a history of myocardial
      infarction (23%), and current status with respect to smoking (74%). There was no
      hospital mortality; 5% of patients had minor postoperative complications.
      RESULTS: After 2 years, the primary patency was 83% for saphenous vein and 67%
      for polytetrafluoroethylene (P =.065); the secondary patency was 83% for
      saphenous vein and 77% for polytetrafluoroethylene (P =.298). During a follow-up
      period of 2 years, we found no statistically significant difference in primary
      and secondary patency between saphenous vein and polytetrafluoroethylene. We
      found no predictive factor for occlusion of either bypass graft. CONCLUSION: The
      use of polytetrafluoroethylene above the knee is a reasonable alternative in
      femoropopliteal bypass grafting that is associated with acceptable short-term
      patency rates.

PMID- 10917988
TI  - The acute effects of intermittent pneumatic foot versus calf versus simultaneous
      foot and calf compression on popliteal artery hemodynamics: a comparative study.
AB  - INTRODUCTION: Intermittent pneumatic compression (IPC) is currently being
      investigated with respect to its effect on distal arterial volume flow in
      patients with peripheral vascular disease. Recently published data have shown a
      substantial acute enhancement in arterial calf inflow in response to IPC of the
      lower limb in both intermittent claudication and leg ischemia. PURPOSE: The aim
      of the study was to compare the immediate effects of intermittent pneumatic foot
      (IPC(foot)) versus calf (IPC(calf)) versus simultaneous foot and calf compression
      (IPC(foot+calf)) on popliteal artery hemodynamics in patients with intermittent
      claudication (Fontaine II) and in normal subjects, using duplex ultrasonography.
      For this purpose, 25 limbs of 20 healthy subjects (age range [mean], 51-74 [64]
      years) and 31 limbs of 25 claudicants (age range [mean], 56-81 [66.5] years;
      resting ankle-brachial indices, 0.38-0.75 [0.55]) were examined in the sitting
      position with and without IPC compression. RESULTS: Mean popliteal artery flow in
      healthy subjects increased by 98.8% on application of IPC(foot), 188% with
      IPC(calf), and 274% with IPC(foot+calf) (all P <.001). Mean flow in claudicants
      increased by 58% on application of IPC(foot), 132% with IPC(calf), and 174% with
      IPC(foot+calf) (all P <.001). The mean velocity, peak systolic velocity, and end
      diastolic velocity displayed a pattern of change similar to that for volume flow
      in both groups. Pulsatility index decreased in both groups on application of IPC;
      the lowest values were generated with IPC(foot+calf). CONCLUSION: Of the three
      compression modes investigated, IPC(foot+calf) was the most effective means of
      acutely augmenting arterial calf inflow in arteriopaths and normals. The
      significant increase in end diastolic velocity and decrease in pulsatility index
      indicate that peripheral vasodilatation is the central mechanism in this impulse
      related flow augmentation. Prospective trials are indicated to determine the
      clinical potential of the long-term effects of IPC(foot+calf) in patients with
      symptomatic peripheral vascular disease.

PMID- 10917990
TI  - The Pruitt-Inahara shunt maintains mean middle cerebral artery velocities within
      10% of preoperative values during carotid endarterectomy.
AB  - OBJECTIVE: The purpose of this study was to assess the ability of the Pruitt
      Inahara shunt to maintain adequate middle cerebral artery velocities during
      carotid endarterectomy. STUDY DESIGN: Prospectively collected data recorded
      during 548 carotid endarterectomies performed at a single university hospital
      were analyzed to look at changes in cerebral blood flow velocities at different
      stages during the procedure. Parallel data relating to blood pressure and end
      tidal carbon dioxide were also examined. RESULTS: During the first carotid artery
      cross clamp, middle cerebral artery velocity fell by 42%. A total of 169 patients
      (31%) had velocities that fell below 15 cm/s (electrical activity in the brain
      becomes altered below this level). After shunt insertion, only 2% of patients had
      middle cerebral artery velocities less than 15 cm/s. In only one patient was the
      velocity less than 10 cm/s. Increased systolic or diastolic blood pressure raised
      flow through the shunt significantly (P =.001). When two criteria used for
      selective shunt use were compared, only a moderate correlation was found between
      absolute middle cerebral artery velocity after carotid cross clamping and
      percentage change in middle cerebral artery velocity relative to preclamp values.
      CONCLUSIONS: The Pruitt-Inahara shunt is able to maintain adequate middle
      cerebral artery velocity in 98% of patients undergoing carotid endarterectomy.
      Alterations in blood pressure can significantly affect flow through the shunt.

PMID- 10917989
TI  - Clinical outcome of patients with internal carotid artery occlusion: a
      prospective follow-up study.
AB  - PURPOSE: We prospectively evaluated whether, and to what extent, different
      clinical presentations (symptomatic or asymptomatic) or the presence of
      atherosclerotic narrowing of the contralateral carotid system modifies the
      mortality rate and the incidence of nonfatal cerebrovascular events in patients
      with internal carotid artery (ICA) occlusion. METHODS: A prospective cohort study
      was conducted in the Unit Care of Angiology at the University Hospital of Padua
      in Italy. Consecutive patients with ICA occlusion were eligible for the study.
      Between 1990 and 1991, 41 such patients were identified at our center. All
      patients were observed prospectively for a mean of 44.5 months, except for one
      patient who was lost to follow-up after 12 months. Patients with severe (ie, more
      than 75%) stenosis of the contralateral internal carotid artery were scheduled
      for thromboendarterectomy. ICA occlusion was objectively documented in all
      patients by using a combination of echo-color Doppler scanning and continuous
      wave Doppler scanning (periorbital flow). RESULTS: The overall mortality rate was
      22.0% (95% CI, 10.6-37.6), and the stroke-related mortality rate was 7.3% (95%
      CI, 1.5-19.9). No differences in overall and stroke-related mortality rates were
      observed between asymptomatic and symptomatic patients. None of the patients
      experienced nonfatal cerebrovascular events. CONCLUSION: ICA occlusion seems to
      represent a relatively benign condition, in both its symptomatic and asymptomatic
      presentation. The presence of an atherosclerotic stenosis less than 75% of the
      contralateral ICA does not seem to worsen the prognosis of this condition.

PMID- 10917991
TI  - Alternative techniques for management of distal anastomoses of aortofemoral and
      iliofemoral endovascular grafts.
AB  - PURPOSE: Techniques for managing the distal anastomoses of aortofemoral and
      iliofemoral endovascular grafts are described. METHODS: Over a 2(1/2)-year period
      46 endovascular grafts were successfully placed to treat severe iliac artery
      occlusive disease. Endovascular grafts were anchored proximally in the distal
      aorta or iliac arteries with Palmaz balloon-expandable stents. The distal
      anastomoses were performed with the use of open, sutured anastomotic techniques.
      In contrast to stented distal anastomoses, these techniques allowed us to (1)
      treat occlusive lesions extending from the distal aorta to below the inguinal
      ligament, (2) terminate endovascular grafts in the groin where stents are
      contraindicated, (3) vary the distal anastomotic site depending on the local
      pattern of disease, and (4) standardize the preinsertion length of the
      endovascular graft. RESULTS: Two distal perianastomotic stenoses and one graft
      occlusion were detected postoperatively in 11 bypass grafts that had distal
      anastomoses sewn endoluminally without an overlying patch angioplasty. Only one
      perianastomotic stenosis was found among 35 anastomoses performed with other
      techniques. There were no significant differences in primary and secondary
      patency between grafts originating in the distal aorta or iliac arteries.
      CONCLUSIONS: Hand-sewn distal anastomoses can simplify the insertion of
      endovascular grafts used for the treatment of aortoiliac occlusive disease. These
      anastomoses permit tailoring of the graft according to the patients' pattern of
      disease and eliminate the need to precisely measure the length of the graft
      preoperatively. In addition, because a distal stent is not required, endovascular
      grafts can be safely terminated in the groin instead of the external iliac artery
      where disease progression can lead to graft failure. Finally, endovascular distal
      anastomoses should be closed with a patch or the hood of a more distal bypass
      graft to prevent perianastomotic stenoses or occlusions in the postoperative
      period.

PMID- 10917992
TI  - Claviculectomy for subclavian venous repair: long-term functional results.
AB  - OBJECTIVES: The purpose of this study was to determine the long-term functional
      results after medial claviculectomy and venous patch angioplasty or bypass
      grafting using internal jugular vein after incomplete thrombolysis of effort
      thrombosis of the subclavian vein. METHODS: The records of 11 patients with
      effort thrombosis who were treated over the past 9 years were reviewed. Patients
      have been followed up between 3 and 9 years at 6-month intervals with duplex
      imaging and contrast venography when indicated and have had an orthopedic
      evaluation of their shoulder function. RESULTS: All reconstructed veins are
      patent, and only one patient complains of any arm swelling after prolonged usage.
      This patient is one of three with postphlebitic changes at the site of repair and
      has similar findings in her basilic vein. All patients have returned to their
      prethrombosis vocation without limitation. Four of the 11 patients have jobs
      requiring heavy physical labor. No patient describes any limitations of shoulder
      function, but one man who works as a diesel mechanic complains of shoulder aching
      with overuse with repetitive pulling. Three patients describe upper extremity
      paresthesias when lying on the operated side. Two patients (one man and one
      woman) are bothered by the large scar and indentation at the site of the
      incision. Every patient considers the overall result completely successful from a
      functional standpoint. CONCLUSIONS: Early subclavian venous repair performed
      through a medial claviculectomy is a durable operation with excellent long-term
      functional results. Half of the patients noted minor but significant symptoms,
      but all are uniformly able to return to normal function.

PMID- 10917993
TI  - Management of leg ulcers in patients with rheumatoid arthritis or systemic
      sclerosis: the importance of concomitant arterial and venous disease.
AB  - PURPOSE: We assessed the etiology and the prevalence of peripheral arterial and
      venous disease in leg ulcers in patients with rheumatoid arthritis and systemic
      sclerosis and analyzed the outcome after treatment of macrovascular disease.
      METHODS: A clinical study on 15 consecutive patients with chronic leg ulcers in
      collagen vascular disease (nine patients with rheumatoid arthritis, six patients
      with systemic sclerosis) was carried out in a referral center. Angiography was
      used when the ankle-arm index was less than 0.8; venography was used when venous
      reflux was detectable by means of a hand-held Doppler examination. Therapies
      included percutaneous transluminal angioplasty (seven patients), femoropopliteal
      bypass grafting surgery (one patient), saphenectomy of the greater saphenous vein
      (six patients), and split skin graft (11 patients). RESULTS: All patients with
      rheumatoid arthritis exhibited a multifactorial etiology of their ulcers: four of
      nine patients had peripheral arterial disease, and five of nine patients had
      venous insufficiency. In one of these patients, arterial and venous disease was
      combined. Five of six patients with systemic sclerosis exhibited a multifactorial
      etiology of their ulcers: three of six patients had peripheral arterial disease,
      and three of six patients had venous insufficiency. One of these patients had
      both arterial and venous disease. In patients with rheumatoid arthritis, healing
      was achieved in six of nine patients, and marked improvement occurred in two of
      nine patients. A below-knee amputation was necessary in one patient with
      rheumatoid vasculitis. In patients with systemic sclerosis, healing was achieved
      in three of six patients, and marked improvement occurred in the other three
      patients. CONCLUSION: Most leg ulcers in patients with rheumatoid arthritis and
      systemic sclerosis disclose a multifactorial etiology. Relevant arterial and
      venous disease can be found in approximately half the patients. Our study
      suggests that revascularization and vein surgery improve the healing of leg
      ulcers in patients with collagen vascular disease. A prospective trial is now
      required to confirm these results.

PMID- 10917994
TI  - Endovenous management of saphenous vein reflux. Endovenous Reflux Management
      Study Group.
AB  - PURPOSE: This study assessed clinical outcomes of two catheter-based endovenous
      procedures to eliminate or greatly mitigate saphenous vein reflux. MATERIALS AND
      METHODS: A computer-controlled, dedicated generator and two catheter designs were
      used to treat 210 patients at 16 private clinic and university centers in Europe.
      The Closure catheter applied resistive heating over long vein lengths to cause
      maximum wall contraction for permanent obliteration; the Restore catheter induced
      a short subvalvular constriction to improve the competence of mobile but
      nonmeeting leaflets. RESULTS: Closure treatment caused acute obliteration in 141
      (93%) of 151 limbs; Restore treatment, shrinking one or more valves, acutely
      reduced reflux to less than 1 second in 41 (60%) of 68 limbs. Closure treatments
      were associated with early recanalization (6%), paresthesias (thigh, 9%; leg,
      51%; P <.001), 3 skin burns, and 3 deep-vein thrombus extensions, with 1
      embolism. Restore treatments were thrombogenic (16%) despite prophylactic
      anticoagulation, and treated valves enlarged over 6 weeks, becoming less
      competent. Clinical Efficacy Assessment Project clinical class was significantly
      improved after both treatments, up to 1 year. At 6 months, 87% of 53 Closure
      patients were class 0 or 1, 75% were symptom-free, and 96% of 55 treated limbs
      were completely free of reflux. Fourteen of 31 Restore patients (45%) had no
      symptoms, but 55% were class 2 or lower and only 19% had less than 1-second
      reflux. CONCLUSION: Closure treatment is clinically effective, albeit with
      offsetting complications and early failures; these are being addressed through
      four procedural modifications. Restore valve shrinking, although conceptually
      attractive, is too problematic to be competitive with Closure treatment or
      saphenectomy.

PMID- 10917995
TI  - Induction of angiogenesis by cationic lipid-mediated VEGF165 gene transfer in the
      rabbit ischemic hindlimb model.
AB  - PURPOSE: The purpose of this study was to test the efficacy of a new cationic
      lipid formulation coupled with the cDNA encoding for the 165-residue form of
      vascular endothelial growth factor (VEGF(165)) to induce neovascularization and
      enhance blood flow in the rabbit ischemic hindlimb model. METHODS: Two days after
      removal of their right femoral arteries, rabbits received intramuscular
      injections of different concentrations of VEGF(165) or saline solution in the
      ischemic thigh. Tissue perfusion and increased neovascularization of the ischemic
      limb were assessed weekly on the basis of the calf blood pressure ratio for the
      ischemic/nonischemic limbs, regional blood flow to the skeletal muscles as
      measured with radioactive microspheres, postmortem angiography, and histology.
      RESULTS: At weeks 1 and 2 after surgery, animals treated with 1000 microgram of
      VEGF(165) had a 1.5-fold increase and a 2.5-fold increase, respectively, in the
      regional blood flow to both the adductor and gastrocnemius muscles of the
      ischemic limb. The blood pressure ratio was also greater in the treated animals
      than in the controls at weeks 2 and 3 after surgery. Early neovascularization in
      the VEGF(165) group was further documented at week 1 after surgery by more
      angiographically recognizable collateral vessels (angioscores were 64.13 +/- 2.51
      and 38.28 +/- 3.82 for VEGF(165) and saline solution, respectively; P <.001) and
      by a threefold increase in the number of capillaries (vascular density) relative
      to the controls (P <.005). CONCLUSIONS: Intramuscular administration of a single
      dose of plasmid-liposomes encoding for VEGF(165) accelerates angiogenesis and
      increases blood flow in the rabbit hindlimb ischemic model. Therefore, this
      nonviral vector could be recommended for further testing for use in therapeutic
      angiogenesis.

PMID- 10917996
TI  - In vivo retention of endothelial cells adenovirally transduced with tissue-type
      plasminogen activator and seeded onto expanded polytetrafluoroethylene.
AB  - PURPOSE: Seeding a prosthetic graft with genetically engineered vascular
      endothelial cells (ECs) has the potential to enhance the graft's antithrombotic
      properties. However, it has been reported that ECs transduced with tissue-type
      plasminogen activator (tPA) have very low levels of retention on grafts, probably
      because of increased proteolytic activity. We examined the retention of human tPA
      (htPA)-transduced ECs after the cells were seeded onto expanded
      polytetrafluoroethylene (ePTFE) grafts and implanted into dogs. We also examined
      the function of secreted htPA in this model. METHODS AND RESULTS: Canine jugular
      venous ECs were transduced with adenoviral vectors encoding htPA (Adex1CAhtPA)
      and beta-galactosidase (Adex1CALacZ). There was a positive relationship between
      the percentage of X-gal ECs staining and the multiplicity of infection (MOI) of
      Adex1CALacZ. The level of htPA production in vitro increased with the increasing
      MOI of Adex1CAhtPA, but decreased gradually 4 days after infection. ECs
      coinfected with Adex1CAhtPA and Adex1CALacZ (htPAEC) or ECs infected with
      Adex1CALacZ alone (LacZEC) were seeded onto ePTFE grafts at densities equivalent
      to confluence to visualize retained ECs in an in vivo flow study. The grafts were
      implanted into canine carotid arteries and harvested after 5 hours of exposure to
      blood flow. The harvested grafts showed patchy defects in ECs, most of which were
      covered with mural thrombi. There was no significant difference in retention
      between htPAEC (29.3% +/- 8.7%) and LacZEC (19.5% +/- 3. 6%). There was a
      significant negative correlation between the in vivo EC retention on the grafts
      and the in vitro cellular passage level of ECs (P =.041; r = -.40). htPAEC
      produced 210.3 +/- 22.2 ng htPA antigen/10(6) cells per 6 hours in vitro and
      continued to secrete htPA on the harvested graft. CONCLUSIONS: We demonstrated
      that a large amount of functional htPA was produced by adenovirally modified
      canine ECs. The results of the in vivo study may suggest that overexpression of
      tPA has little effect on the short-term retention of early passage ECs seeded
      onto ePTFE grafts.

PMID- 10917997
TI  - Opioid growth factor modulates angiogenesis.
AB  - OBJECTIVE: Induced angiogenesis has recently been attempted as a therapeutic
      modality in patients with occlusive arterial atherosclerotic disease. We
      investigated the possible role of endogenous opioids in the modulation of
      angiogenesis. METHODS: Chick chorioallantoic membrane was used as an in vivo
      model to study angiogenesis. Fertilized chick eggs were incubated for 3 days,
      explanted, and incubated for an additional 2 days. Three-millimeter
      methylcellulose disks were placed on the surface of the chorioallantoic membrane;
      each disk contained opioid growth factor ([Met(5)]-enkephalin; 5 microgram), the
      short-acting opioid receptor antagonist naloxone (5 microgram), opioid growth
      factor and naloxone together (5 microgram of each), the long-acting opioid
      antagonist naltrexone (5 microgram), or distilled water (control). A second
      series of experiments was performed with distilled water, the angiogenic
      inhibitor retinoic acid (1 microgram), and vascular endothelial growth factor (1
      microgram) to further evaluate our model. The developing vasculature was imaged 2
      days later with a digital camera and exported to a computer for image analysis.
      Total number of blood vessels, total vessel length, and mean vessel length were
      measured within a 100-mm(2) region surrounding each applied disk.
      Immunocytochemical analysis was performed with antibodies directed against opioid
      growth factor and its receptor (OGFr). RESULTS: Opioid growth factor had a
      significant inhibitory effect on angiogenesis, both the number of blood vessels
      and the total vessel length being decreased (by 35% and 20%, respectively) in
      comparison with control levels (P <.005). The simultaneous addition of naloxone
      and opioid growth factor had no effect on blood vessel growth, nor did naloxone
      alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51%
      and 24% in blood vessel number and length, respectively, in comparison with
      control specimens (P <.005). These results indicate that the opioid growth factor
      effects are receptor mediated and tonically active. Immunocytochemistry
      demonstrated the presence of both opioid growth factor and OGFr within the
      endothelial cells and mesenchymal cells of the developing chorioallantoic
      membrane vessel wall. Retinoic acid significantly reduced the number and the
      total length of blood vessels, whereas vascular endothelial growth factor
      increased both the number and the length of blood vessels in comparison with the
      controls (P <.0001). The magnitude of opioid growth factor's effects were
      comparable to those seen with retinoic acid, whereas inhibition of opioid growth
      factor with naltrexone induced an increase in total vessel length comparable to
      that for vascular endothelial growth factor. CONCLUSIONS: These results
      demonstrate for the first time that endogenous opioids modulate in vivo
      angiogenesis. Opioid growth factor is a tonically active peptide that has a
      receptor-mediated action in regulating angiogenesis in developing endothelial and
      mesenchymal vascular cells.

PMID- 10917998
TI  - High accumulation of plasminogen and tissue plasminogen activator at the flow
      surface of mural fibrin in the human arterial system.
AB  - PURPOSE: We assessed the fibrinolytic activity of the organized mural thrombus
      lining of aneurysms and prosthetic grafts. METHODS: Between May 1995 and April
      1998, the full-thickness mural thrombi of aneurysms and the pseudointima lining
      of vascular grafts were obtained from 12 patients, ranging from 55 to 78 years in
      age, who underwent elective surgery. These included five aortic arch aneurysms,
      four abdominal aortic aneurysms, and three patent synthetic vascular grafts. The
      specimens were subjected to sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE)/immunoblot and immunohistochemistry for human
      plasmin/plasminogen, tissue plasminogen activator (tPA), and fibrin degradation
      product (D-dimer). RESULTS: In the SDS-PAGE/immunoblot, 25- and 27-kd bands
      appeared specifically in experimental fibrin plates after limited digestion by
      plasmin and were also recognized in the mural thrombi. The presence of bands at
      25 and 27 kd, which were most prominent in sections near the flow surface layer,
      was consistent with the hypothesis that the mural fibrin was digested by the
      endogenous plasmin. Apparent immunoreactivity was found at the flow surface of
      the masses at a thickness of 10 to 400 micrometer suggesting the presence of a
      plasminogen and tPA-rich layer, with D-dimer as a consequential product of
      fibrinolysis. CONCLUSION: The hypothesis that fibrin surfaces in the arterial
      system acquire fibrinolytic activity because of digestion by circulating
      endogenous plasmin was confirmed; this may contribute to the antithrombogenicity
      of these flow surfaces.

PMID- 10917999
TI  - Idiopathic pedunculated mural thrombus of the nonaneurysmal infrarenal aorta
      presenting with popliteal embolization: two cases treated with thrombolytic
      therapy.
AB  - The source of emboli to large or medium sized arteries is most commonly the
      heart; occasionally, it is an aortic aneurysm. The unusual embolic source of
      aortic mural thrombus in an otherwise minimally diseased aorta has been
      infrequently reported, and the etiology and management of this entity are not
      well defined. We describe two cases of infrarenal aortic mural thrombus treated
      with thrombolytic therapy and review the published experience with this entity.

PMID- 10918000
TI  - De novo renal artery aneurysm presenting 6 years after transplantation: a
      complication of recurrent arterial stenosis?
AB  - Pseudoaneurysms represent a well-recognized vascular complication of renal
      transplantation, but true aneurysms involving the donor renal artery have not
      been described. We report a patient who had a de novo aneurysm of the donor renal
      artery 6 years after receiving a cadaveric renal transplant from a child. The
      aneurysm was repaired successfully, and allograft function was preserved.
      Histologic evidence confirmed that the lesion was a true aneurysm. Given the
      potential for graft loss associated with complications of unrepaired aneurysms,
      we believe that the presence of a true aneurysm in a donor renal artery
      represents an indication for repair.

PMID- 10918002
TI  - Complicated emergent endovascular repair of a life-threatening bilateral internal
      jugular vein occlusion.
AB  - A 62-year-old woman had painful facial swelling that progressed to extensive
      periorbital and perioral edema with loss of vision, hearing, and consciousness.
      Her past surgical history was significant for right radical neck dissection
      including internal jugular vein (IJV) resection, laryngectomy, partial
      esophagectomy, tracheoesophageal fistula repair, and tracheostomy for squamous
      cell carcinoma of the oropharynx. In addition, the patient had received radiation
      therapy to the neck. A venogram revealed occlusion of the left IJV. A guidewire
      from the femoral vein was passed through the occluded segment; however, attempts
      to introduce an angioplasty balloon failed. A percutaneous basilic vein approach
      allowed passage of a dilator sheath over a guidewire, thereby enabling Wallstent
      deployment across the IJV occlusion. A second Wallstent was inserted across a
      stenosis in the brachiocephalic vein; however, this second stent reoccluded the
      IJV. Surgical removal of the second Wallstent was required through a segmental
      claviculectomy and venotomy. Patency was restored in the IJV and the
      brachiocephalic vein with the return of baseline neurologic function. This case
      demonstrates a complicated emergent endovascular repair of a life-threatening IJV
      occlusion that required surgical salvage.

PMID- 10918003
TI  - P values may lack power: the choice of conduit for above-knee femoropopliteal
      bypass graft.

PMID- 10918001
TI  - Crushed stents in benign left brachiocephalic vein stenoses.
AB  - Two hemodialysis patients presenting with left venous arm congestion due to
      benign catheter-induced stenosis of the left brachiocephalic vein were treated by
      angioplasty and stent placement. External compression of the stents was
      responsible for rapid recurrence of the symptoms. No osseous or vascular
      malformation could be identified. Mechanical constraints induced by respiratory
      chest wall motion and aortic arch flow-related pulsation are proposed to explain
      this observation. This potential hazard should be considered when stent placement
      into the left brachiocephalic vein is advocated.

PMID- 10918004
TI  - Kazi mobin-uddin, 1930-1999

PMID- 10918005
TI  - Regarding "emergency repair of thoracoabdominal aortic aneurysms: a word of
      caution on the numerical analysis of the results".

PMID- 10918006
TI  - Reply

PMID- 10918007
TI  - A brief history of chronic subdural hematomas.
AB  - Examination of human remains tells us that subdural hematomas have been with
      mankind for thousands of years. Their recognition as distinct clinical entities
      is considerably more recent, and it has only been in the last century that the
      cause of chronic subdural hematomas has been adequately elucidated. The history
      of this discovery process is interesting and sheds light on the nature of
      scientific progress in general.

PMID- 10918008
TI  - Causes, epidemiology, and risk factors of chronic subdural hematoma.
AB  - Chronic subdural hematoma is an important reversible cause of dementia and
      disability in the elderly. A sufficiently high level of clinical suspicion and
      prompt radiographic evaluation may allow for timely treatment to avoid poor
      outcomes. Thankfully, the routine use of computed tomographic scanning in most
      emergency facilities has made the diagnosis of these lesions commonplace.

PMID- 10918009
TI  - The outer neomembrane of chronic subdural hematoma.
AB  - Thomas Willis recognized the entity of the chronic subdural hematoma (CSH) more
      than 300 years ago. Modern observations of the ultrastructure of normal meninges
      and the CSH outer neomembrane, combined with techniques of radioactive red blood
      cell labeling and chemical analysis of CSH fluid, have provided insight into the
      pathophysiology of this entity. The outer membrane evolves as a reaction to
      cleavage of the dural border cell layer of the meninges. Interaction between the
      components of the outer neomembrane and CSH fluid contributes to the growth of
      the outer membrane and recurrent hemorrhaging.

PMID- 10918010
TI  - The inner membrane of chronic subdural hematomas: pathology and pathophysiology.
AB  - There is no clear plane between the dura and arachnoid in situ. Instead of the
      virtual subdural space, there is a dura-arachnoid interface layer, which is
      structurally the weakest throughout the meninges. An extravasation of blood
      within the dural border layer splits it, leaving a few tiers of dural border
      cells over the arachnoid. These cells cover the internal surface of the hematoma,
      proliferate, and later on, form the inner membrane. The outer membrane is related
      to hematoma enlargement because of the repetitive hemorrhages whereas the inner
      membrane is related to liquefaction of the subdural hematoma. As the inner
      membrane plays a pivotal role in the pathophysiogenesis and determination of the
      location of chronic subdural hematoma, histologic, ultrastructural, and clinical
      analyses were performed with correlations to the dura-arachnoid interface and the
      so-called "subdural space."

PMID- 10918011
TI  - Contents of chronic subdural hematoma.
AB  - Analysis of chronic subdural hematoma membranes and contents has revealed a
      complex process of blood breakdown forming a milieu that stimulates
      neovascularization and repeated hemorrhage.

PMID- 10918012
TI  - Pathophysiology of evolution and recurrence of chronic subdural hematoma.
AB  - Although the pathophysiology of the development, propagation, and recurrence of
      current subdural hematoma remains debatable, fundamental management strategies
      may be formulated to optimize outcomes. Effective drainage by whatever surgical
      means, removal of offending membranes when appropriate, and maximization of
      postoperative physiologic parameters are based on the best available current
      pathophysiologic information.

PMID- 10918013
TI  - Chronic subdural hematoma in children.
AB  - Chronic subdural hematoma (CSH) is generally a disease affecting the elderly and
      infants. In infants, the process is particularly confusing and frequently
      misunderstood. In the pediatric population, CSH is just one of a group of
      sometimes related conditions known as extracerebral fluid collections. In the
      past, extracerebral fluid collections, in general, and CSHs, in particular, have
      been inaccurately or incompletely described. Modern neuroimaging techniques,
      however, have greatly advanced our understanding of these conditions.
      Surprisingly little literature exists on the subject, and publications before the
      advent of modern computed tomography and magnetic resonance imaging should be
      interpreted with caution.

PMID- 10918014
TI  - Chronic subdural hematoma in adult and elderly patients.
AB  - Chronic subdural hematomas display a wide diversity of features in adults, often
      simulating other neurologic and psychiatric disease processes. This is
      particularly problematic in elderly patients, for whom more nonspecific clinical
      presentations are common. Recognition of these features is the key to early
      diagnosis in elderly patients, who exhibit a markedly increased incidence of this
      disease. Prompt diagnosis prevents delays that may lead to increased morbidity in
      these patients.

PMID- 10918015
TI  - Interhemispheric and bilateral chronic subdural hematoma.
AB  - Data on bilateral chronic subdural hematomas (CSHs) are scant, including
      information on the frequency of symptoms, response to various treatments, and
      postoperative complications, compared with data on unilateral CSH. Bilateral CSHs
      constitute a fair portion of CSHs, especially in patients older than 75 years and
      in those with coagulation abnormalities. The presenting symptoms are those of
      increased intracranial pressure and mass effect. Computed tomography of the head
      is the best study for the diagnosis and follow-up of bilateral CSHs, although
      magnetic resonance imaging is a more sensitive modality. Treatment of bilateral
      CSHs presents its own unique set of problems. New hemorrhage on the contralateral
      side and shift of midline structures are concerns and can be avoided by
      simultaneous bilateral decompression. Twist-drill craniostomy, burr-hole washout,
      and craniotomy are the mainstays of treatment, with subdural-peritoneal shunting
      reserved for intractable cases.

PMID- 10918016
TI  - Spinal chronic subdural hematoma.
AB  - Although chronic subdural hematomas are rare, they are likely to be more
      frequently reported as the clinical and magnetic resonance imaging
      characteristics become defined. Chronic spinal subdural hematomas (CSSDH) are
      extremely rare; these hematomas are frequently spontaneous and related to minor
      trauma. Although generally said to carry a poor prognosis, CSSDH can be a
      reversible cause of paraplegia. This article reviews the history, classification,
      clinical presentation, and treatment of CSSDH.

PMID- 10918017
TI  - Clinical features of chronic subdural hematoma: neuropsychiatric and
      neuropsychologic changes in patients with chronic subdural hematoma.
AB  - This article provides a background review of the cognitive and behavioral
      symptoms associated with chronic subdural hematoma (CSH). The areas addressed
      include the initial cognitive and behavioral symptom presentation, lateralization
      and localizing signs, differences between older and younger patients, and
      differential diagnosis. Although it is clear that behavioral and cognitive
      abnormalities are seen in CSH, further work is needed to objectively clarify the
      range of symptoms and signs.

PMID- 10918018
TI  - Computed tomographic characteristics of chronic subdural hematomas.
AB  - Although medical history and physical examination should lead to diagnosis of
      chronic subdural hematomas, 40% of these patients are likely to be misdiagnosed
      because many of these symptoms occur in other disease processes, such as
      transient ischemic attacks, stroke, dementia, and tumors. Computed tomography
      remains one of the most useful tools in the evaluation of these patients because
      of its rapidity, cost, availability, and pathologic sensitivity.

PMID- 10918019
TI  - Magnetic resonance imaging of chronic subdural hematoma.
AB  - This article highlights the unique ability of magnetic resonance imaging in
      evaluating the evolution of the subdural hematoma. Topics specifically discussed
      are computed tomography sensitivity and the extent, age, and complexity of the
      subdural hematoma.

PMID- 10918020
TI  - Regional cerebral blood flow and metabolism in chronic subdural hematoma.
AB  - There are two hypotheses on how chronic subdural hematoma causes hemiparesis and
      other focal neurologic symptoms without, in most cases, leaving permanent
      neurologic deficits. One hypothesis is that the reduced regional cerebral blood
      flow (rCBF) caused by either compression or distortion of the local or remote
      brain tissue is responsible for hemiparesis. The other hypothesis is that the
      reduction in rCBF alone is not sufficient to cause permanent hemiparesis.

PMID- 10918021
TI  - Treatment of chronic subdural hematoma by burr holes and closed-system drainage.
AB  - This article highlights the treatment of choice of chronic subdural hematoma. The
      importance, effectiveness, and low complication rate of minimally invasive
      procedure by burr holes and closed-system drainage is discussed.

PMID- 10918022
TI  - Nonoperative treatment of chronic subdural hematoma.
AB  - Chronic subdural hematomas that are asymptomatic or producing only mild symptoms
      are occasionally found with current neuroimaging methods. Some do not progress,
      and spontaneous resolution can occur. In addition, successful medical treatment
      of more significant hematomas has been reported. The indications for nonoperative
      management of these lesions are reviewed in this article.

PMID- 10918023
TI  - Twist-drill craniostomy for the treatment of chronic subdural hematoma.
AB  - The choice of the initial surgical method for treating the patient with CSH is
      influenced by the patient's neurologic status at the time of presentation,
      associated medical factors, and the surgeon's experience in the management of
      these patients. The outcome data suggest that twist-drill craniostomy with closed
      system catheter drainage results in an equivalent or superior outcome to the
      historical results of craniotomy with membranectomy. Craniotomy remains the
      treatment of choice when the admitting computerized tomographic scan demonstrates
      a significant hyperdense component suggesting the presence of solid or mixed
      hematoma.

PMID- 10918024
TI  - Percutaneous subdural tapping and subdural peritoneal drainage for the treatment
      of subdural hematoma.
AB  - Different therapeutic approaches may be used in the treatment of chronic subdural
      hematoma because it is more fluid. Age-dependent characteristics of the calvarium
      allow for different treatment in children and adults. Treatment options are
      discussed.

PMID- 10918026
TI  - The role of craniotomy and trephination in the treatment of chronic subdural
      hematoma.
AB  - The treatment of chronic subdural hematoma by craniotomy was the procedure of
      choice in the early part of this century. It has since been replaced by less
      invasive techniques but retains a limited role in the management of this
      condition. A new procedure involving a small craniectomy and marsupialization of
      the hematoma cavity to the temporalis muscle is described. The results of this
      treatment compare favorably with the more commonly performed drainage methods.

PMID- 10918025
TI  - Neuroendoscopic treatment of loculated chronic subdural hematoma.
AB  - Treatment of loculated chronic subdural hematoma using endoscopic operative
      techniques combined with closed-system draining is a minimally invasive method
      and a therapeutic alternative to the craniotomy-membranectomy technique.

PMID- 10918027
TI  - The course of chronic subdural hematomas after burr-hole craniostomy with and
      without closed-system drainage.
AB  - The author provides a comprehensive review of the results of surgical treatment
      of chronic subdural hematomas (CSHs). The postoperative clinical course of CSH is
      studied with respect to the influence of neomembranous organization, cortical
      expansion, and subdural pressure. The importance of subdural drainage is
      emphasized.

PMID- 10918028
TI  - Postoperative complications of chronic subdural hematomas: prevention and
      treatment.
AB  - The treatment of chronic subdural hematoma seems simple and effective; however,
      postoperative complications like recurrence of hematoma, pneumocephalus brain
      collapse, and intracervical hemorrhage still occur in some patients, and these
      complications are dependent on surgical technique, patient's age, and preexisting
      morbidity.

PMID- 10918029
TI  - Prognosis of chronic subdural hematomas.
AB  - This article considers factors that may be of prognostic value in evaluating the
      chronic subdural hematoma (CSH) patient. It also examines conditions that
      predispose the development of a CSH. Variables such as admission neurologic
      status and presenting symptomatology are reviewed. Radiologic parameters (i.e.,
      CSH density and midline shift) and intraoperative findings (i.e., pressure and
      pulse) are discussed.

PMID- 10918030
TI  - A cortisol surge mediates the enhanced expression of pig intestinal pyrroline-5
      carboxylate synthase during weaning.
AB  - Citrulline synthesis from glutamine is enhanced remarkably in enterocytes of
      weanling pigs, but the molecular mechanism(s) involved are not known. The
      objective of this study was to determine whether a cortisol surge mediates the
      enhanced expression of intestinal citrulline-synthetic enzymes during weaning.
      Jejunal enterocytes were prepared from 29-d-old weanling pigs treated with or
      without metyrapone (an inhibitor of cortisol synthesis), or from age-matched
      unweaned pigs. The mRNA levels and activities of phosphate-dependent glutaminase
      (PDG), pyrroline-5-carboxylate synthase (P5CS), ornithine aminotransferase (OAT),
      carbamoyl-phosphate synthase I (CPS-I) and ornithine carbamoyltransferase (OCT)
      were determined. The mRNA levels for PDG, P5CS, OAT and OCT were 139, 157, 102
      and 55% higher, respectively, in weanling pigs compared with suckling pigs. The
      activities of PDG and P5CS were 38 and 692% higher, respectively, in weanling
      pigs compared with unweaned pigs, but the activities of OAT, CPS-I and OCT did
      not differ between these two groups of pigs. The effects of metyrapone
      administration to weanling pigs were as follows: 1) prevention of a cortisol
      surge, 2) abolition of the increases in both mRNA levels and activity of P5CS, 3)
      no alteration in the mRNA levels and activities of PDG and CPS-I, 4) increases in
      the mRNA levels for OAT (216%) and OCT (39%) and in OAT activity (30%), and 5)
      prevention of the increase in intestinal synthesis of citrulline from glutamine.
      These results suggest that increased P5CS activity reflects in large part the
      increased levels of P5CS mRNA and is responsible for the increased synthesis of
      citrulline from glutamine in enterocytes of weanling pigs; these increases may be
      mediated by a cortisol surge during weaning that can be blocked by metyrapone
      administration.

PMID- 10918031
TI  - B-cell epitope mapping of the Neisseria meningitidis P64k protein using
      overlapping peptides.
AB  - A common meningococcal antigen designated P64k has been identified, cloned and
      expressed in Escherichia coli. The recombinant antigen is highly immunogenic in
      several animal species and its immunogenicity in healthy human volunteers is
      under investigation. Recently, P64k has been used as an immunological carrier for
      weak immunogens. To characterize the B-cell epitopes on P64k, recognized by
      immune sera obtained from mice, rabbits and monkeys, multiple overlapping
      peptides were synthesized and screened for antibody binding. Peptides covering
      the complete sequence of the P64k protein, 59 in all, of 20 amino acids each
      (overlapped by 10 residues), were synthesized. A number of continuous epitopes
      were detected with all sera, when immune and pre-immune bleeds were compared. For
      mouse and monkey sera, a few major antigenic peptides were identified, while the
      recognition of the rabbit serum was much more heterogeneous. Despite variation in
      the exact location of continuous epitopes defined by different anti-P64k sera, we
      found an immunogenic core region within the molecule, composed of amino acids
      Asp(524)-Gly(533). Consistently, in this protein segment there was an amino acid
      stretch located in a beta-hairpin loop, which is exposed to the solvent in the
      previously determined three-dimensional structure of the protein. This region is
      protruding and accessible to a sphere with a radius of 9 A.

PMID- 10918032
TI  - A bioelectrode for penicillin detection based on gluten-membrane-entrapped
      microbial cells.
AB  - A bioelectrode for penicillin detection was established using gluten membrane in
      which cells of Escherichia coli harbouring the plasmid pUC18 coding for
      penicillinase synthesis were entrapped. For the entrapment preparation,
      lyophilized cells were mixed with gluten solution during the formation of gel,
      and the resultant gel was hardened by the addition of oxidized starch. The
      immobilization procedure employed an inexpensive base material and avoided the
      use of purified enzyme. When the membrane with a thickness of 30 microm and a
      cell content of 33% (w/w) was used, the steady response of the bioelectrode to
      increasing concentrations of penicillin G buffered with 0.025 M phosphate was
      linear over the range of 1-16 mM. The response time was less than 3 min.
      Decreasing the cell content decreased the steady response due to a decline in
      enzymic activity. The treatment of lyophilized cells with ultrasonication or
      chemically with either N-cetyl-N,N,N-trimethylammonium bromide or guanidine
      hydrochloride rendered cells permeabilized and exposed the periplasmic enzyme to
      penicillin. The response time became shorter, but a serious decline in steady
      responses was observed because of the loss of enzyme activity during the cell
      permeabilization. The microbial electrode also showed different responses to
      penicillin G solution, depending on the pH and buffer concentration.

PMID- 10918033
TI  - Development of allergen-coated paper discs for allergy diagnosis by ELISA.
AB  - In vitro testing is useful for detecting pollen and fungal-allergen sensitivities
      in nasobronchial-allergy patients. However, allergen-coated discs or solid-phases
      supplied in kits do not contain all the relevant extracts. The present study was
      aimed to develop a safe and credible procedure of allergen coating on paper discs
      for allergy diagnosis by ELISA. Paper discs were coated with indigenous allergens
      using poly(vinyl alcohol) and glutaraldehyde. ELISAs were carried out to
      standardize the allergen-coated discs using skin-test-positive-patients' sera.
      The cut-off value (A) for ELISA was worked out by analysing normal human sera
      (NHS) and is based on the mean+/-2 S.D. for the NHS value. The allergen-coated
      discs, i.e. Centre for Biochemical Technology (CBT) discs, demonstrated excellent
      comparison with plate-binding method and Pharmacia discs [Prosopis juliflora
      (mesquite), critical value 0.879 at 5% probability+/-0.599, n=11, is
      significant]. Inter- and Intra-assay coefficients of variations ranged from 2.5
      14.05% to 4. 8-11.5% with different allergens. Results of skin tests and ELISA
      with CBT discs showed 60-70% correlation.

PMID- 10918034
TI  - Improvement of receptor-mediated gene delivery to HepG2 cells using an
      amphiphilic gelling agent.
AB  - Gene transfer was performed using asialo-oroso-mucoid-polylysine (ASOR-PL)
      conjugates to allow targeted expression of the gene in cells of hepatic origin.
      In a gel-electrophoretic analysis, the ASOR-PL conjugate produced a complete DNA
      retardation effect at the optimal ratio of 222:1 (ASOR-PL conjugate/pCMV beta-gal
      plasmid). The gene-transfer efficiency of the ASOR-PL conjugate was evaluated in
      HepG2 cells that express asialoglycoprotein receptor and NIH 3T3 cells that do
      not. The expression was assayed by 5-bromo-4-chloroindol-3-yl beta-D
      galactopyranoside ('X-Gal') staining and Chlorophenol Red beta-D
      galactopyranoside. When an expression vector for the tumour-suppressor gene p53,
      pCMVp53, complexed to ASOR-PL conjugate, was transfected into HepG2 cells, the
      exogenously provided p53 gene was detected in the HepG2 cells by PCR. To improve
      the efficiency of DNA delivery and expression of the therapeutic proteins
      poloxamer 407, a fusogenic peptide, influenza-virus haemagglutinin HA2 and
      chloroquine were individually incorporated into the system. The expression level
      of beta-galactosidase in HepG2 cells was increased by about four times by the
      presence of poloxamer 407, whereas the fusogenic peptide HA2 and chloroquine had
      no effects. When HepG2 cells were transfected with pCMVp53 in the presence of
      poloxamer 407, the mRNA of transfected p53 could be detected by reverse
      transcriptase PCR. The current findings open the possibility that a receptor
      mediated gene-delivery system for hepatic gene therapy using ASOR-PL conjugate in
      combination with poloxamer 407 may be developed in the future.

PMID- 10918035
TI  - Differences in the post-translational modifications of human papillomavirus type
      6b major capsid protein expressed from a baculovirus system compared with a
      vaccinia virus system.
AB  - Virus-like particles (VLPs) are being currently investigated in vaccines against
      viral infections in humans. There are different recombinant-protein-expression
      systems available for obtaining the necessary VLP preparation for vaccination.
      However, the differences in post-translational modifications of the recombinant
      proteins obtained and their differences in efficacy in eliciting an anti-viral
      response in vaccines are not well established. In this study we have compared the
      post-translational modifications of human papillomavirus type-6b major capsid
      protein L1 (HPV 6bL1) expressed using recombinant baculovirus (rBV) in Sf9
      (Spodoptera frugiperda) insect cells, with the protein expressed using
      recombinant vaccinia virus (rVV) in CV-1 kidney epithelial cells. Two-dimensional
      gel electrophoresis of biosynthetically labelled rBV-expressed HPV 6bL1 showed
      several post-translationally modified variants of the protein, whereas rVV
      expressed HPV 6bL1 showed only a few variants. Phosphorylations were detected at
      threonine and serine residues for the L1 expressed from rBV compared with
      phosphorylation at serine residues only for the L1 expressed from rVV. HPV 6bL1
      expressed using rBV incorporated [(3)H]mannose and [(3)H]galactose, whereas HPV
      6bL1 expressed using rVV incorporated only [(3)H]galactose. We conclude that post
      translational modification of recombinant HPV 6bL1 can differ according to the
      system used for its expression. Since recombinant L1 protein is a potential human
      vaccine candidate, the implication of the observed differences in post
      translational modifications on immunogenicity of L1 VLPs warrants investigation.

PMID- 10918036
TI  - A kinetic study of the synthesis of ascorbate fatty acid esters catalysed by
      immobilized lipase in organic media.
AB  - The kinetics of the synthesis of L-ascorbyl laurate and L-ascorbyl palmitate
      catalysed by immobilized lipase from L-ascorbic acid and an acyl donor (lauric
      acid, palmic acid and their methyl and ethyl esters) in 2-methylbutan-2-ol have
      been investigated. The factors affecting the reaction rate (shaking speed,
      temperature, water activity, enzyme concentration as well as substrate
      concentration) are discussed. The reaction conditions have been optimized as
      follows: shaking speed 200 rev./min, temperature 55 degrees C, enzyme 17-20% (w/w
      of substrate) for these substrates. The most suitable substrate concentration for
      all of these substrates was 300 mmol/l. The reactions were modelled. For lauric
      acid, methyl laurate and ethyl laurate: K(m)=74.3, 48.97 and 55.8 mmol/l,
      respectively; and V(max)=0.010764, 0.0114, 0.01116 mmol.min(-1).g(-1),
      respectively. The most suitable substrate was methyl laurate. For palmic acid,
      methyl palmitate and ethyl palmitate: K(m)=102, 94.9 and 104 mmol/l,
      respectively; and V(max)=0.0417, 0.0424 and 0.0435 mmol.min(-1).g(-1),
      respectively. The most suitable substrate was methyl palmitate.

PMID- 10918037
TI  - Carbohydrate structures of soluble human L-selectin recombinantly expressed in
      baby-hamster kidney cells.
AB  - A soluble form of L-selectin was recombinantly produced, which might be an
      effective therapeutic agent in inflammatory disorders, acting as an inhibitor for
      leucocyte endothelium adhesion. In the present study the oligosaccharide
      structures of soluble human L-selectin, recombinantly expressed in baby-hamster
      kidney cells, were determined. The N-linked glycans were enzymically released and
      fluorescently labelled with 2-aminobenzamide. Sialylation of the N-glycans was
      analysed by anion-exchange chromatography followed by rechromatography of the
      resulting fractions on amino-phase HPLC after release of the sialic acid
      residues. Desialylated oligosaccharides were separated using two-dimensional HPLC
      and characterized by digestion with exoglycosidases and MS. More than 30
      oligosaccharide structures representing at least 95% of the overall glycosylation
      of this protein were determined. The results revealed that recombinant soluble
      human L-selectin carries bi-, tri- and tetra-antennary sugar chains, which are
      fucosylated on the innermost residue of N-acetylglucosamine. The number of sialic
      acid residues linked to these glycans ranges from 0 (neutral glycans) to 4
      (tetrasialylated oligosaccharides). The sialic acid is found exclusively in the
      alpha 2-3 linkage to galactose. In addition to the main glycans, different minor
      structures containing terminal N-acetylgalactosamine, or the H (O) blood-group
      determinant were also identified. O-Glycosylation of mucin-type sugar chains was
      not detected in recombinant soluble human L-selectin.

PMID- 10918038
TI  - Effect of amino acid substitution at the P(3) and P(4) subsites of fusion
      proteins on kex2 protease activity.
AB  - The effect of amino acid substitution at the P(3) and P(4) subsites on the
      cleavage activity of a recombinant secretory-type Kex2 protease (Kex2-660) was
      investigated using recombinant fusion proteins. They were constructed from a
      truncated Escherichia coli beta-galactosidase (beta G-117S) followed by human
      parathyroid hormone amino acids 1-34 [hPTH(1-34)] with a junction designed to
      allow cleavage with Kex2-660. Kex2-660 preferentially cleaved the fusion protein
      with Arg-His at the P(3)-P(4) subsite, whereas it poorly cleaved the fusion
      proteins with Val-Asp, Gly-His, Cys-His and Leu-His compared with the original
      sequence, Val-Lys. As for Asp and Glu at P(4), they precluded the cleavage almost
      completely. Some of the substitutions were investigated kinetically using the
      fusion proteins and peptide-substrate mimics corresponding to the 15 amino acids
      contained in the junction. The substitution Val-Lys to Arg-His resulted in a 2
      fold increase in k(cat) and the introduction of Asp at P(4) of the peptide
      substrate resulted in a large increase in K(m) and a change in the optimum pH.
      The ordered cleavage of the fusion protein was attained by introducing the two
      dibasic sites, Arg-His and Asp-His, at P(4)-P(3). The fusion protein was cleaved
      with Kex2 only at the former site in 3.0 M urea at pH 8.0 and the liberated
      peptides containing the latter site could be cleaved further with Kex2 at pH 6.5
      once purified in urea-free solution. Thus Kex2 exhibited extended substrate
      specificity beyond P(2)-P(1) in the cleavage of the fusion proteins, although it
      depended on the reaction conditions.

PMID- 10918039
TI  - Inhibitory and lytic effects of phenothiazine derivatives and related tricyclic
      neuroleptic compounds, on Entamoeba histolytica HK9 and HM1 trophozoites.
AB  - It has been shown previously that tricyclic neuroleptics like clomipramine and
      chlorpromazine have lethal effects on Leishmania donovani and L. major, and other
      studies indicate that the phenothiazine inhibitors of trypanothione reductase are
      potential anti-trypanosomal and anti-leishmanial drugs. With this in mind and our
      original observation on the presence of trypanothione in Entamoeba histolytica
      HK9, we examined the possible inhibitory effects of various phenothiazine and
      tricyclic derivatives on this human parasite. We found that drugs like
      clomipramine (KD002), the most potent in vitro inhibitor of trypanothione
      reductase among 30 tricyclic compounds tested, at 25 microM after 24 h of culture
      under aerobic conditions, caused a substantial decrease in the number of E.
      histolytica HK9 trophozoites, from approx. 15 x 10(6) to 5.37 x 10(6) cells, and
      at 100 microM to 0.8 x 10(6) cells. A substantial inhibitory effect on cell
      proliferation could also be demonstrated with metronidazol (used clinically
      against amoebiasis). Under similar experimental conditions other tricyclic and
      phenothiazine derivatives (OFKs), designed originally to inhibit the
      trypanothione reductase of trypanosomatides, had an inhibitory effect of 16 to
      95%. For comparison, similar results were obtained using clomipramine and a
      phenothiazine derivative (OFK006) with Trypanosoma cruzi and Crithidia luciliae,
      except that with the latter the inhibitory effect of clomipramine was less
      dramatic. Experiments comparing two E. histolytica strains showed that normal
      cell proliferation under anaerobiosis was higher in strain HK9 than in HM1, which
      is highly virulent, but that metronidazol and clomipramine were less effective
      against HM1. Two other drugs tested, diphenydramine (KD005) and a phenothiazine
      derivative (OFK008), also had significant but lower inhibitory effects on both
      strains. The inhibitory activity on cell proliferation and the lytic effects on
      this human parasite by the tricyclic compounds clomipramine, chlorpromazine and
      others, as well as by the phenothiazine derivatives, indicate that they can be
      considered potential anti-amoebic agents.

PMID- 10918040
TI  - Anthrax toxin-mediated delivery of cholera toxin-A subunit into the cytosol of
      mammalian cells.
AB  - The protective antigen (PA) component of anthrax toxin mediates delivery of
      either lethal factor (LF) or oedema factor into the cytosol of mammalian cells.
      The N-terminal domain of LF(1-254) (amino acids 1-254 of LF) binds to PA and,
      when fused to heterologous proteins, delivers such proteins into the cytosol. In
      the present study, we fused the catalytic subunit of cholera toxin (CT-A) with
      LF(1-254) and showed that the fusion protein LF(1-254)-CT-A retains ADP
      ribosylation activity in solution and increased intracellular cAMP levels in
      J774A.1 macrophage cells when added together with PA. A mutant fusion protein, in
      which arginine-7 of CT-A was replaced with lysine, did not show ADP-ribosylation
      activity in solution and failed to increase cAMP levels in macrophage cells. The
      data show that LF(1-254)-CT-A retains its catalytic activity in solution as well
      as when translocated into the cytosol of eukaryotic cells via an alternative
      pathway to the GM(1) receptor used by CT.

PMID- 10918041
TI  - Gene delivery via polyomavirus major capsid protein VP(1), isolated from
      recombinant Escherichia coli.
AB  - In this study we attempted to investigate the feasibility of transferring
      exogenous DNA into the recipient host via polyomavirus major capsid protein VP(1)
      pseudocapsids generated from recombinant Escherichia coli, designated PyVP(1,E),
      both in vitro and in vivo. NIH-3T3 and FR3T3 cells were transfected with pCMV
      beta and pPyMT-1 plasmid DNA, respectively. In vitro DNA transfection was carried
      out via Pseudofect- and PyVP(1,E)-mediated methods, or by co-precipitation with
      calcium phosphate. Expression of beta-galactosidase and PyMT reporter genes was
      examined by Western-blot analysis. Parallel experiments were performed in vivo by
      direct injection of pCMV beta and pPyMT-1 plasmid DNA, complexed with PyVP(1,E),
      into the livers of Wistar rats, followed by Western-blot analysis and
      histochemical staining. The results obtained from in vitro transfection
      experiments showed that expression of the reporter genes can be detected in the
      recipient cells at 48 h post-transfection. PyVP(1,E) was shown to exhibit
      similarly efficient in vitro DNA transfection properties to Pseudofect, which was
      obtained from recombinant baculovirus.

PMID- 10918043
TI  - Analysis of the candidate genes responsible for non-syndromic cleft lip and
      palate in Japanese people.
AB  - In order to assess the association of alleles for candidate genes with non
      syndromic cleft lip and palate, DNA samples from 43 Japanese patients were
      compared with those from 73 control subjects with respect to the genes encoding
      transforming growth factor alpha (TGFalpha), TGFbeta and gamma-aminobutyric acid
      type A receptor beta3 (GABRB3). The restriction fragment length polymorphisms of
      the 3'-non-coding region of the TGFalpha gene K-primer region were observed after
      digestion with NcoI and HinfI. Allele 4 was the most common among cases of cleft
      lip with or without cleft palate, whereas allele 2 was the most common among
      controls. A significant difference was found in this region between groups with
      cleft lip (with or without cleft palate) and controls (chi2=10.190; P=0.017).
      Three alleles of the TGFbeta2 gene were tested, and allele 2 was the most common
      in both cases and controls. The proportion of allele 2 in the case group was
      greater than that in the control group, showing a significant difference between
      cases of cleft lip (with or without cleft palate) and controls (chi(2)=19.208;
      P<0.0001). No significant differences in variants of TGFbeta3 or GABRB3 between
      case and control populations were observed. Thus it is concluded that TGF genes
      play a role in craniofacial development, and that alleles of TGFalpha or/and
      TGFbeta2 are associated with cleft lip and cleft palate in Japanese populations.

PMID- 10918042
TI  - A guardian angel: the involvement of dipeptidyl peptidase IV in
      psychoneuroendocrine function, nutrition and immune defence.
AB  - Dipeptidyl peptidase IV (DPP IV, also known as CD26; EC 3.4.14.5) is a non
      integrin receptor glycoprotein with multiple functions, including cell adhesion,
      cellular trafficking through the extracellular matrix and co-stimulatory
      potential during T cell activation. By virtue of its exopeptidase activity, DPP
      IV plays a key regulatory role in the metabolism of peptide hormones. Based on
      data emerging from different biomedical specialties, it appears worthwhile to
      highlight the different facets of DPP IV in nutrition, immune responses and
      peptide hormone metabolism. The presentation of the complex regulatory circuits
      in which DPP IV appears to be involved may also serve as a note of caution, in
      view of attempts to apply selective inhibitors of DPP IV enzymic activity for the
      treatment of disease, e.g. Type II diabetes.

PMID- 10918044
TI  - Cardiocirculatory coupling during sinusoidal baroreceptor stimulation and fixed
      frequency breathing.
AB  - The question of whether respiratory sinus arrhythmia (RSA) originates mainly from
      a central coupling between respiration and heart rate, or from baroreflex
      mechanisms, is a subject of controversy. If there is a major contribution of
      baroreflexes to RSA, cardiocirculatory coupling during breathing and during
      cyclic baroreflex stimulation should show similarities. We applied a sinusoidal
      stimulus to the carotid baroreceptors and generated heart rate fluctuations of
      the same magnitude as RSA with a frequency similar to, but different from, the
      breathing frequency (0.2 Hz, compared with 0.25 Hz), and at 0.1 Hz, in 17 supine
      healthy subjects (age 28-39 years). The data were analysed using discrete Fourier
      transform and transfer function analysis. Respiratory fluctuations in systolic
      blood pressure preceded RSA with a time lag equal to that between baroreceptor
      stimulation and oscillations in RR interval (0.62+/-0.18 s compared with 0.57+/
      0.28 s at 0.2 Hz neck suction). The response of systolic blood pressure to neck
      suction at 0.2 Hz was 5 times less than the respiratory blood pressure
      fluctuations. Neck suction at 0.1 Hz largely increased fluctuations in blood
      pressure and RR interval, whereas the spontaneous phase relationship between
      blood pressure and RR interval remained unchanged. Our results are not consistent
      with the hypothesis that the origin of RSA is predominantly a central phenomenon
      which secondarily generates fluctuations in blood pressure, but suggest that,
      under the condition of fixed-frequency breathing at 0.25 Hz, baroreflex
      mechanisms contribute to respiratory fluctuations in RR interval.

PMID- 10918045
TI  - Very-low-frequency oscillations in heart rate and blood pressure in periodic
      breathing: role of the cardiovascular limb of the hypoxic chemoreflex.
AB  - In chronic heart failure, very-low-frequency (VLF) oscillations (0.01-0.04 Hz) in
      heart rate and blood pressure may be related to periodic breathing, although the
      mechanism has not been fully characterized. Groups of ten patients with chronic
      heart failure and ten healthy controls performed voluntary periodic breathing
      with computer guidance, while ventilation, oxygen saturation, non-invasive blood
      pressure and RR interval were measured. In air, voluntary periodic breathing
      induced periodic desaturation and prominent VLF oscillations when compared with
      free breathing in both patients [RR interval spectral power from 179 to 358 ms2
      (P<0.05); systolic blood pressure (SBP) spectral power from 3.44 to 6.25 mmHg2
      (P<0.05)] and controls [RR spectral power from 1040 to 2307 ms2 (P<0.05); SBP
      spectral power from 3.40 to 9.38 mmHg2 (P<0.05)]. The peak in RR interval
      occurred 16-26 s before that in SBP, an anti-baroreflex pattern. When the
      patients followed an identical breathing pattern in hyperoxic conditions to
      prevent desaturation, the VLF RR interval spectral power was 50% lower (179.0+/
      51.7 ms2; P<0.01) and the VLF SBP spectral power was 44% lower (3.51+/-0.77
      mmHg(2); P<0.01); similar effects were seen in controls (VLF RR power 20% lower,
      at 1847+/-899 ms2, P<0.05; VLF SBP power 61% lower, at 3.68+/-0.92 mmHg2,
      P=0.01). Low- and high-frequency spectral powers were not significantly affected.
      Thus periodic breathing causes oxygen-sensitive (and by implication chemoreflex
      related) anti-baroreflex VLF oscillations in RR interval and blood pressure in
      both patients with chronic heart failure and normal controls.

PMID- 10918047
TI  - Transvenous echo Doppler in baboons: a new window to the cardiovascular system.
AB  - Ultrasound examinations of the heart and major peripheral arteries have been
      performed as separate procedures; both potentially limited by suboptimal views in
      certain subjects and the inability to obtain ideal pictures of particular
      intracardiac structures. Transvenous ultrasound may offer new advantages in
      certain areas, we therefore studied six adult baboons using a single-plane 5.5-10
      MHz transducer mounted on a 10 French (10F) catheter, introduced via the right
      femoral vein and positioned under fluoroscopic control. Imaging and Doppler
      studies were performed to delineate cardiovascular anatomy as well as ventricular
      function response to positive (dobutamine) and negative inotropic (esmolol)
      agents. The procedure was safe and feasible in all cases. Clear and novel two
      dimensional and flow information were obtained from the iliac arteries,
      descending aorta, both renal artery origins, ascending aorta, including the
      aortic arch, main pulmonary artery and its bifurcation, as well as head and neck
      vessels. Novel intracardiac views were obtained, including right ventricular long
      axis, left ventricular apex and 'flask' views of the left ventricle. Excellent
      dynamic information for left ventricular function was also available [e.g.
      myocardial Vmax of the anterior left ventricular wall was 6.8+/-2.5 cm/s at rest,
      14.6+/-5.5 cm/s after dobutamine (P=0.009) and 4.5+/-1 cm/s after esmolol (P=0.03
      compared with control)]. We conclude that, in adult primates, transvenous
      ultrasound safely and reliably provides novel information of cardiovascular
      structure and function.

PMID- 10918046
TI  - Induction of osteoclasts from CD14-positive human peripheral blood mononuclear
      cells by receptor activator of nuclear factor kappaB ligand (RANKL).
AB  - Osteoclasts are bone-resorbing cells that are derived from haemopoietic
      precursors, including cells present in peripheral blood. The recent
      identification of RANKL [receptor activator of nuclear factor (NF)-kappaB
      ligand], a new member of the tumour necrosis factor ligand superfamily that has a
      key role in osteoclastogenesis, has allowed the in vitro generation of
      osteoclasts in the absence of cells of the stromal/osteoblast lineage. Human
      peripheral blood mononuclear cells (PBMC) cultured in vitro with soluble RANKL
      and human macrophage colony-stimulating factor form osteoclasts. However, PBMC
      are heterogeneous, consisting of subsets of monocytes and lymphocytes as well as
      other blood cells. As the CD14 marker is strongly expressed on monocytes, the
      putative osteoclast precursor in peripheral blood, we have selected CD14(+) cells
      from PBMC to examine their osteoclastogenic potential and their expression of
      novel members of the tumour necrosis factor superfamily involved in
      osteoclastogenesis. Highly purified CD14(+) cells demonstrated mRNA expression of
      receptor activator of NF-kappaB, but no expression of RANKL or osteoprotegerin,
      whereas PBMC expressed mRNAs for all three factors. CD14(+) (but not CD14(-))
      cells cultured on bone slices for 21 days with human macrophage colony
      stimulating factor and soluble RANKL generated osteoclasts and showed extensive
      bone resorption. Similar numbers of osteoclasts were generated by 10(5) CD14(+)
      cells and 10(6) PBMC, but there was significantly less intra-assay variability
      with CD14(+) cells, suggesting the absence of stimulatory/inhibitory factors from
      these cultures. The ability of highly purified CD14(+) cells to generate
      osteoclasts will facilitate further characterization of the phenotype of
      circulating osteoclast precursors and cell interactions in osteoclastogenesis.

PMID- 10918048
TI  - Do we need another echo 'window to the cardiovascular system'?

PMID- 10918049
TI  - Organization and reorganization of human swallowing motor cortex: implications
      for recovery after stroke.
AB  - Swallowing problems can affect as many as one in three patients in the period
      immediately after a stroke. In some cases this can lead to serious morbidity, in
      particular malnutrition and pulmonary aspiration. Despite this, swallowing
      usually recovers to a safe level in the majority of patients within weeks. This
      propensity for recovery is likely to relate to how the swallowing motor cortex is
      organized and then reorganized after cerebral injury. In this review, we examine
      present knowledge on the cortical control of swallowing in humans, and examine
      the aspects of its organization that are important for compensating for recovery
      after damage. In addition, we examine approaches which may be useful in speeding
      up the process of recovery. Swallowing may turn out to be a useful model for
      studying central nervous system plasticity.

PMID- 10918050
TI  - Circulating vascular endothelial growth factor levels are decreased in patients
      with chronic hepatitis and liver cirrhosis depending on the degree of hepatic
      damage.

PMID- 10918051
TI  - Transmembrane phosphoprotein Cbp positively regulates the activity of the
      carboxyl-terminal Src kinase, Csk.
AB  - Csk (carboxyl-terminal Src kinase) is a cytoplasmic tyrosine kinase that
      phosphorylates a critical tyrosine residue in each of the Src family kinases
      (SFKs) to inhibit their activities. Recently, we identified a transmembrane
      protein, Cbp (Csk-binding protein), that, when phosphorylated, can recruit Csk to
      the membrane where the SFKs are located. The Cbp-mediated relocation of Csk to
      the membrane may play a role in turning off the signaling events initiated by
      SFKs. To further characterize the Csk-Cbp interaction, we have generated a
      reconstituted system using soluble, highly purified proteins. Csk and
      phosphorylated Cbp were co-purified as a large protein complex consisting of at
      least four Csk.Cbp units. The addition of the phosphorylated, but not
      nonphosphorylated, Cbp to an in vitro assay stimulated Csk activity toward Src.
      Csk was also activated by a phosphopeptide containing the tyrosine in Cbp that
      binds to Csk (Tyr-314). Kinetic analysis revealed that Cbp or the phosphopeptide
      induced up to a 6-fold reduction in the K(m) for Src, indicating that the Csk.Cbp
      complex has a greater affinity for Src than free Csk. These findings suggest that
      Cbp is involved in the regulation of SFKs not only by relocating Csk to the
      membrane but also by directly activating Csk.

PMID- 10918052
TI  - Dimerization of bovine F1-ATPase by binding the inhibitor protein, IF1.
AB  - In mitochondria, the hydrolytic activity of ATP synthase is regulated by a
      natural inhibitor protein, IF(1). The binding of IF(1) to ATP synthase depends on
      pH values, and below neutrality, IF(1) forms a stable complex with the enzyme.
      Bovine IF(1) has two oligomeric states, dimer and tetramer, depending on pH
      values. At pH 6.5, where it is active, IF(1) dimerizes by formation of an
      antiparallel alpha-helical coiled-coil in its C-terminal region. This arrangement
      places the inhibitory N-terminal regions in opposition, implying that active
      dimeric IF(1) can bind two F(1) domains simultaneously. Evidence of dimerization
      of F(1)-ATPase by binding to IF(1) is provided by gel filtration chromatography,
      analytical ultracentrifugation, and electron microscopy. At present, it is not
      known whether IF(1) can bring about the dimerization of the F(1)F(0)-ATPase
      complex.

PMID- 10918053
TI  - HCaRG, a novel calcium-regulated gene coding for a nuclear protein, is
      potentially involved in the regulation of cell proliferation.
AB  - Since a negative calcium balance is present in spontaneously hypertensive rats,
      we searched for the gene(s) involved in this dysregulation. A cDNA library was
      constructed from the spontaneously hypertensive rat parathyroid gland, which is a
      key regulator of serum-ionized calcium. From seven overlapping DNA fragments, a
      1100-base pair novel cDNA containing an open reading frame of 224 codons was
      reconstituted. This novel gene, named HCaRG (hypertension-related, calcium
      regulated gene), was negatively regulated by extracellular calcium concentration,
      and its basal mRNA levels were higher in hypertensive animals. The deduced
      protein showed no transmembrane domain, 67% alpha-helix content, a mutated
      calcium-binding site (EF-hand motif), four putative "leucine zipper" motifs, and
      a nuclear receptor-binding domain. At the subcellular level, HCaRG had a nuclear
      localization. We cloned the human homolog of this gene. Sequence comparison
      revealed 80% homology between rats and humans at the nucleotide and amino acid
      sequences. Tissue distribution showed a preponderance in the heart, stomach,
      jejunum, kidney (tubular fraction), liver, and adrenal gland (mainly in the
      medulla). HCaRG mRNA was significantly more expressed in adult than in fetal
      organs, and its levels were decreased in tumors and cancerous cell lines. We
      observed that after 60-min ischemia followed by reperfusion, HCaRG mRNA declined
      rapidly in contrast with an increase in c-myc mRNA. Its levels then rose steadily
      to exceed base line at 48 h of reperfusion. HEK293 cells stably transfected with
      HCaRG exhibited much lower proliferation, as shown by cell count and
      [(3)H]thymidine incorporation. Taken together, our results suggest that HCaRG is
      a nuclear protein potentially involved in the control of cell proliferation.

PMID- 10918054
TI  - Activation of protein kinase C induces nuclear translocation of RFX1 and down
      regulates c-myc via an intron 1 X box in undifferentiated leukemia HL-60 cells.
AB  - Treatment of human promyelocytic leukemia cells (HL-60) with phorbol 12-myristate
      13-acetate (PMA) is known to decrease c-myc mRNA by blocking transcription
      elongation at sites near the first exon/intron border. Treatment of HL-60 cells
      with either PMA or bryostatin 1, which acutely activates protein kinase C (PKC),
      decreased the levels of myc mRNA and Myc protein. The inhibition of Myc synthesis
      accounted for the drop in Myc protein, because PMA treatment had no effect on Myc
      turnover. Treatment with PMA or bryostatin 1 increased nuclear protein binding to
      MIE1, a c-myc intron 1 element that defines an RFX1-binding X box. RFX1 antiserum
      supershifted MIE1-protein complexes. Increased MIE1 binding was independent of
      protein synthesis and abolished by a selective PKC inhibitor, which also
      prevented the effect of PMA on myc mRNA and protein levels and Myc synthesis. PMA
      treatment increased RFX1 in the nuclear fraction and decreased it in the cytosol
      without affecting total RFX1. Transfection of HL-60 cells with myc reporter gene
      constructs showed that the RFX1-binding X box was required for the down
      regulation of reporter gene expression by PMA. These findings suggest that
      nuclear translocation and binding of RFX1 to the X box cause the down-regulation
      of myc expression, which follows acute PKC activation in undifferentiated HL-60
      cells.

PMID- 10918056
TI  - Presence of oxidized cholesterol in caveolae uncouples active platelet-derived
      growth factor receptors from tyrosine kinase substrates.
AB  - Platelet-derived growth factor receptor beta (PDGFRbeta) in fibroblasts is
      concentrated in caveolae where it controls the tyrosine phosphorylation of
      multiple proteins. Caveolae are enriched in cholesterol and sphingolipids, but
      the role of these lipids in PDGFR signal transduction is unknown. We report that
      introduction of cholest-4-en-3-one into caveolae membranes uncouples PDGFR
      autophosphorylation from tyrosine phosphorylation of neighboring proteins.
      Cholest-4-en-3-one appears to interfere with the normal interaction between PDGFR
      and its partners. The results suggest that tightly packed caveolae lipids form a
      membrane platform that functions as a lipid scaffold for organizing the molecular
      interactions of multiple signaling pathways.

PMID- 10918055
TI  - Isolation and characterization of apolipoproteins from murine microglia.
      Identification of a low density lipoprotein-like apolipoprotein J-rich but E-poor
      spherical particle.
AB  - Amyloid Abeta deposition is a neuropathologic hallmark of Alzheimer's disease.
      Activated microglia are intimately associated with plaques and appear to
      facilitate Abeta deposition, an event believed to contribute to pathogenesis. It
      is unclear if microglia can modulate pathogenesis of Alzheimer's disease by
      secreting lipoprotein particles. Here we show that cultured BV2 murine microglial
      cells, like astrocytes, secrete apolipoprotein E (apoE) and apolipoprotein J
      (apoJ) in a time-dependent manner. To isolate and identify BV2 microglial
      particles, gel filtration chromatography was employed to fractionate BV2
      conditioned medium. Analyses by Western blot, lipid determination, electron
      microscopy, and native gel electrophoresis demonstrate that BV2 microglial cells
      release spherical low density lipoprotein (LDL)-like lipid-containing particles
      rich in apoJ but poor in apoE. These microglial particles are dissimilar in size,
      shape, and lipoprotein composition to astrocyte-derived particles. The microglial
      derived particles were tested for functional activity. Under conditions of
      suppressed de novo cholesterol synthesis, the LDL-like particles effectively
      rescued primary rat cortical neurons from mevastatin-induced neurotoxicity. The
      particles were also shown to bind Abeta. We speculate that the LDL-like apoJ-rich
      apoE-poor microglial lipoproteins preferentially bind the lipoprotein receptor,
      recognizing apoJ, which is abundant in the choroid plexus, facilitating Abeta
      clearance from the brain. BV2 cells also secrete an apoE-rich lipid-poor species
      that binds Abeta. Consistent with the role of apoE in Abeta fibril formation and
      deposition, this microglial species may promote plaque formation.

PMID- 10918057
TI  - Nuclear localization of enzymatically active green fluorescent protein
      CTP:phosphocholine cytidylyltransferase alpha fusion protein is independent of
      cell cycle conditions and cell types.
AB  - To address the recent controversy about the subcellular localization of
      CTP:phosphocholine cytidylyltransferase alpha (CTalpha), this study was designed
      to visualize green fluorescent protein (GFP). CTalpha fusion proteins directly
      and continuously under different conditions of cell cycling and in various cell
      lines. The GFP. CTalpha fusion proteins were enzymatically active and capable of
      rescuing mutant cells with a temperature-sensitive CT. The expressed GFP.CTalpha
      fusion protein was localized to the nucleus in all cell lines and required the N
      terminal nuclear targeting sequence. Serum depletion/replenishment did not cause
      shuttling of CTalpha between the nucleus and cytoplasm. Moreover, the subcellular
      localization of CTalpha was examined continuously through all stages of the cell
      cycle in synchronized cells. No shuttling of CTalpha between the nucleus and
      cytoplasm was observed at any stage of the cell cycle. Stimulation of cells with
      oleate had no effect on the localization of CTalpha. The GFP.CTalpha lacking the
      nuclear targeting sequence stayed exclusively in the cytoplasm. Regardless of
      their localization, the GFP.CTalpha fusion proteins were equally active for
      phosphatidylcholine synthesis and mutant rescue. We conclude that the nuclear
      localization of CTalpha is a biological event independent of cell cycle in most
      mammalian cells and is unrelated to activation of phosphatidylcholine synthesis.

PMID- 10918058
TI  - Specific binding of a 14-3-3 protein to autophosphorylated WPK4, an SNF1-related
      wheat protein kinase, and to WPK4-phosphorylated nitrate reductase.
AB  - WPK4 is a wheat protein kinase related to the yeast protein kinase SNF1, which
      plays a role in catabolite repression. To identify proteins involved in signal
      transduction through WPK4, we performed yeast two-hybrid screens and isolated two
      cDNA clones designated as TaWIN1 and TaWIN2. Both encode 14-3-3 proteins that,
      upon autophosphorylation, bind the C-terminal regulatory domain of WPK4.
      Mutational analysis through amino acid substitution revealed that TaWIN1 and
      TaWIN2 primarily bind WPK4 through phosphoserines at the positions 388 and 418,
      both located in the C-terminal region. Mutations in the conserved residues of the
      TaWIN1 amphipathic groove impaired the ability of TaWIN1 to bind to WPK4. A
      screen for in vitro phosphorylation of proteins involved in nutrient metabolism
      revealed a putative WPK4 substrate, nitrate reductase; its hinge 1 region was
      efficiently phosphorylated by WPK4. Subsequent far Western blots showed that it
      specifically bound TaWIN1. Since nitrate reductase has been shown to be
      inactivated by phosphorylation upon 14-3-3 binding, the present findings strongly
      suggest that WPK4 is the protein kinase responsible for controlling the nitrogen
      metabolic pathway, assembling the nitrate reductase and 14-3-3 complex through
      its phosphorylation specificity.

PMID- 10918059
TI  - A domain with homology to neuronal calcium sensors is required for calcium
      dependent activation of diacylglycerol kinase alpha.
AB  - Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol produced during
      stimulus-induced phosphoinositide turnover and attenuate protein kinase C
      activation. Diacylglycerol kinase alpha is an 82-kDa DGK isoform that is
      activated in vitro by Ca(2+). The DGK alpha regulatory region includes tandem C1
      protein kinase C homology domains and Ca(2+)-binding EF hand motifs. It also
      contains an N-terminal recoverin homology (RVH) domain that is related to the N
      termini of the recoverin family of neuronal calcium sensors. To probe the
      structural basis of Ca(2+) regulation, we expressed a series of DGK alpha
      deletions spanning its regulatory domain in COS-1 cells. Deletion of the RVH
      domain resulted in loss of Ca(2+)-dependent activation. Further deletion of the
      EF hands resulted in a constitutively active enzyme, suggesting that sequences in
      or near the EF hands are sufficient for autoinhibition. Binding of Ca(2+) to the
      EF hands protected sites within both the RVH domain and EF hands from trypsin
      cleavage and increased the phenyl-Sepharose binding of a recombinant DGK alpha
      fragment that included both the RVH domain and EF hands. These observations
      suggested that Ca(2+) elicits a concerted conformational change of these two
      domains. A cationic amphiphile, octadecyltrimethylammonium chloride, also
      activated DGK alpha. As with Ca(2+), this activation required the RVH domain.
      However, this agent did not protect the EF hands and RVH domain from trypsin
      cleavage. These findings indicate that the EF hands and RVH domain act as a
      functional unit during Ca(2+)-induced DGK alpha activation.

PMID- 10918060
TI  - Promoter trapping of a novel medium-chain acyl-CoA oxidase, which is induced
      transcriptionally during Arabidopsis seed germination.
AB  - The first step of peroxisomal fatty acid beta-oxidation is catalyzed by a family
      of acyl-CoA oxidase isozymes with distinct fatty acyl-CoA chain-length
      specificities. Here we identify a new acyl-CoA oxidase gene from Arabidopsis
      (AtACX3) following the isolation of a promoter-trapped mutant in which beta
      glucuronidase expression was initially detected in the root meristem. In acx3
      mutant seedlings medium-chain acyl-CoA oxidase activity was reduced by 95%,
      whereas long- and short-chain activities were unchanged. Despite this reduction
      in activity lipid catabolism and seedling development were not perturbed. AtACX3
      was cloned and expressed in Escherichia coli. The recombinant enzyme displayed
      medium-chain acyl-CoA substrate specificity. Analysis of beta-glucuronidase
      activity in acx3 revealed that, in addition to constitutive expression in the
      root axis, AtACX3 is also up-regulated strongly in the hypocotyl and cotyledons
      of germinating seedlings. This suggests that beta-oxidation is regulated
      predominantly at the level of transcription in germinating oilseeds. After the
      discovery of AtACX3, the Arabidopsis acyl-CoA oxidase gene family now comprises
      four isozymes with substrate specificities that encompass the full range of acyl
      CoA chain lengths that exist in vivo.

PMID- 10918061
TI  - A structure-function analysis of serine/threonine phosphorylation of the
      thrombopoietin receptor, c-Mpl.
AB  - Thrombopoietin (TPO), the critical regulator of platelet production, acts by
      binding to its cell surface receptor, c-Mpl. Numerous studies have shown that TPO
      binding leads to JAK2 kinase activation and Tyr phosphorylation of c-Mpl and
      several intracellular signaling intermediates, events vital for the biological
      activity of the hormone. In contrast, virtually nothing is known of the role of
      Ser or Thr phosphorylation of c-Mpl. By using phosphoamino acid analysis we found
      that Ser residues of c-Mpl were constitutively phosphorylated in receptor-bearing
      cells, levels that were increased following exposure of cells to TPO. To identify
      which residues were modified, and to determine the functional consequences of
      their phosphorylation, we generated a series of Ser to Ala mutations of a
      truncated c-Mpl receptor (T69) capable of supporting TPO-induced cell growth. Of
      the eight Ser within T69 we found that at least four are phosphorylated in TPO
      stimulated cells. The mutation of each of these residues alone had minimal
      effects on TPO-induced proliferation, but substitution of all of the
      phosphoserine residues with Ala reduced the capacity of the receptor to support
      cell growth by over 50%. Additionally, the Ser at cytoplasmic position 18 is not
      detectably phosphorylated. However, the mutation of Ser-18 to Ala nearly
      abrogates TPO-induced proliferation and co-precipitation of JAK2 with Mpl. This
      study provides the first systematic analysis of the role of Ser residues in c-Mpl
      signaling.

PMID- 10918062
TI  - Metabolism of D-aminoacyl-tRNAs in Escherichia coli and Saccharomyces cerevisiae
      cells.
AB  - In Escherichia coli, tyrosyl-tRNA synthetase is known to esterify tRNA(Tyr) with
      tyrosine. Resulting d-Tyr-tRNA(Tyr) can be hydrolyzed by a d-Tyr-tRNA(Tyr)
      deacylase. By monitoring E. coli growth in liquid medium, we systematically
      searched for other d-amino acids, the toxicity of which might be exacerbated by
      the inactivation of the gene encoding d-Tyr-tRNA(Tyr) deacylase. In addition to
      the already documented case of d-tyrosine, positive responses were obtained with
      d-tryptophan, d-aspartate, d-serine, and d-glutamine. In agreement with this
      observation, production of d-Asp-tRNA(Asp) and d-Trp-tRNA(Trp) by aspartyl-tRNA
      synthetase and tryptophanyl-tRNA synthetase, respectively, was established in
      vitro. Furthermore, the two d-aminoacylated tRNAs behaved as substrates of
      purified E. coli d-Tyr-tRNA(Tyr) deacylase. These results indicate that an
      unexpected high number of d-amino acids can impair the bacterium growth through
      the accumulation of d-aminoacyl-tRNA molecules and that d-Tyr-tRNA(Tyr) deacylase
      has a specificity broad enough to recycle any of these molecules. The same
      strategy of screening was applied using Saccharomyces cerevisiae, the tyrosyl
      tRNA synthetase of which also produces d-Tyr-tRNA(Tyr), and which, like E. coli,
      possesses a d-Tyr-tRNA(Tyr) deacylase activity. In this case, inhibition of
      growth by the various 19 d-amino acids was followed on solid medium. Two isogenic
      strains containing or not the deacylase were compared. Toxic effects of d
      tyrosine and d-leucine were reinforced upon deprivation of the deacylase. This
      observation suggests that, in yeast, at least two d-amino acids succeed in being
      transferred onto tRNAs and that, like in E. coli, the resulting two d-aminoacyl
      tRNAs are substrates of a same d-aminoacyl-tRNA deacylase.

PMID- 10918063
TI  - Phorbol ester-induced expression of airway squamous cell differentiation marker,
      SPRR1B, is regulated by protein kinase Cdelta /Ras/MEKK1/MKK1-dependent/AP-1
      signal transduction pathway.
AB  - The transcriptional induction of SPRR1B by phorbol 12-myristate 13-acetate (PMA)
      is mainly mediated by the first -152-base pair 5'-flanking region containing two
      functional AP-1 sites. In this study, we have analyzed the signaling pathways
      that mediate the induction in tracheobronchial epithelial cells. PKC inhibitor
      ablated PMA-stimulated expression of endogenous SPRR1B and reporter gene
      expression driven by SPRR1B promoter. PKC activator promoted the transcription.
      The dominant negative protein kinase Cdelta (dn-PKCdelta) and rottlerin (PKCdelta
      inhibitor) completely suppressed PMA-stimulated promoter activity. dn-Ras or dn
      MEKK1 inhibited PMA-stimulated promoter activity, while their corresponding
      constitutively active mutants augmented it. dn-c-Raf-1 did not have any effect on
      reporter gene expression. Since MEKK1 activates multiple parallel pathways, we
      examined involvement of JNK/SAPK, p38, and MKK1 in promoter regulation. Co
      expression of the dominant negative forms of MKK4, MKK7, JNK/SAPK, MKK3, MKK6, or
      p38alpha did not suppress PMA-stimulated reporter gene expression. However, MKK1
      inhibitors UO126 and PD98095 suppressed gene expression. Consistent with this,
      expression of dn-MKK1 strongly suppressed PMA-stimulated promoter activity, while
      the constitutively active MKK1 augmented it. However, MKK1-mediated induction of
      SPRR1B probably does not depend on extracellular signal-regulated kinases 1 and
      2, suggesting the requirement of another kinase(s). dn-c-Jun mutants abolished
      PMA-stimulated expression supporting an important role for AP-1 proteins in
      SPRR1B expression. Together, these results suggest that a PKCdelta/Ras/MEKK1/MKK1
      dependent/AP-1 pathway regulates the PMA-inducible expression of the SPRR1B in
      tracheobronchial epithelial cells.

PMID- 10918064
TI  - Promoter analysis of the mouse sterol regulatory element-binding protein-1c gene.
AB  - Recent data suggest that sterol regulatory-binding protein (SREBP)-1c plays a key
      role in the transcriptional regulation of different lipogenic genes mediating
      lipid synthesis as a key regulator of fuel metabolism. SREBP-1c regulates its
      downstream genes by changing its own mRNA level, which led us to sequence and
      analyze the promoter region of the mouse SREBP-1c gene. A cluster of putative
      binding sites of several transcription factors composed of an NF-Y site, an E
      box, a sterol-regulatory element 3, and an Sp1 site were located at -90 base
      pairs of the SREBP-1c promoter. Luciferase reporter gene assays indicated that
      this SRE complex is essential to the basal promoter activity and confers
      responsiveness to activation by nuclear SREBPs. Deletion and mutation analyses
      suggest that the NF-Y site and SRE3 in the SRE complex are responsible for SREBP
      activation, although the other sites were also involved in the basal activity.
      Gel mobility shift assays demonstrate that SREBP-1 binds to the SRE3. Taken
      together, these findings implicate a positive loop production of SREBP-1c through
      the SRE complex, possibly leading to the overshoot in induction of SREBP-1c and
      its downstream genes seen in the livers of refed mice. Furthermore, reporter
      assays using larger upstream fragments indicated another region that was
      inducible by addition of sterols. The presence of the SRE complex and a sterol
      inducible region in the same promoter suggests a novel regulatory link between
      cholesterol and fatty acid synthesis.

PMID- 10918066
TI  - Gene-specific trans-regulatory functions of magnesium for chloroplast mRNA
      stability in higher plants.
AB  - In higher plant chloroplasts the accumulation of plastid-encoded mRNAs during
      leaf maturation is regulated via gene-specific mRNA stabilization. The half-lives
      of chloroplast RNAs are specifically affected by magnesium ions. psbA mRNA (D1
      protein of photosystem II), rbcL mRNA (large subunit of ribulose-1,5-bisphosphate
      carboxylase), 16 S rRNA, and tRNA(His) gain stability at specific magnesium
      concentrations in an in vitro degradation system from spinach chloroplasts. Each
      RNA exhibits a typical magnesium concentration-dependent stabilization profile.
      It shows a cooperative response of the stability-regulated psbA mRNA and a
      saturation curve for the other RNAs. The concentration of free Mg(2+) rises
      during chloroplast development within a range sufficient to mediate gene-specific
      mRNA stabilization in vivo as observed in vitro. We suggest that magnesium ions
      are a trans-acting factor mediating differential mRNA stability.

PMID- 10918065
TI  - Specific binding of ApoA-I, enhanced cholesterol efflux, and altered plasma
      membrane morphology in cells expressing ABC1.
AB  - Mutations of the ABC1 transporter have been identified as the defect in Tangier
      disease, characterized by low HDL and cholesterol ester accumulation in
      macrophages. A full-length mouse ABC1 cDNA was used to investigate the mechanisms
      of lipid efflux to apoA-I or HDL in transfected 293 cells. ABC1 expression
      markedly increased cellular cholesterol and phospholipid efflux to apoA-I but had
      only minor effects on lipid efflux to HDL. The increased lipid efflux appears to
      involve a direct interaction between apoA-I and ABC1, because ABC1 expression
      substantially increased apoA-I binding at the cell surface, and chemical cross
      linking and immunoprecipitation analysis showed that apoA-I binds directly to
      ABC1. In contrast to scavenger receptor BI (SR-BI), another cell surface molecule
      capable of facilitating cholesterol efflux, ABC1 preferentially bound lipid-free
      apoA-I but not HDL. Immunofluorescence confocal microscopy showed that ABC1 is
      primarily localized on the cell surface. In the absence of apoA-I, cells
      overexpressing ABC1 displayed a distinctive morphology, characterized by plasma
      membrane protrusions and resembling echinocytes that form when there are excess
      lipids in the outer membrane hemileaflet. The studies provide evidence for a
      direct interaction between ABC1 and apoA-I, but not HDL, indicating that free
      apoA-I is the metabolic substrate for ABC1. Plasma membrane ABC1 may act as a
      phospholipid/cholesterol flippase, providing lipid to bound apoA-I, or to the
      outer membrane hemileaflet.

PMID- 10918067
TI  - Selected mutations in a mesophilic cytochrome c confer the stability of a
      thermophilic counterpart.
AB  - Mesophilic cytochrome c(551) of Pseudomonas aeruginosa (PA c(551)) became as
      stable as its thermophilic counterpart, Hydrogenobacter thermophilus cytochrome
      c(552) (HT c(552)), through only five amino acid substitutions. The five
      residues, distributed in three spatially separated regions, were selected and
      mutated with reference to the corresponding residues in HT c(552) through careful
      structure comparison. Thermodynamic analysis indicated that the stability of the
      quintuple mutant of PA c(551) could be partly attained through an enthalpic
      factor. The solution structure of the mutant showed that, as in HT c(552), there
      were tighter side chain packings in the mutated regions. Furthermore, the mutant
      had an increased total accessible surface area, resulting in great negative
      hydration free energy. Our results provide a novel example of protein
      stabilization in that limited amino acid substitutions can confer the overall
      stability of a natural highly thermophilic protein upon a mesophilic molecule.

PMID- 10918068
TI  - Characterization of RasGRP2, a plasma membrane-targeted, dual specificity Ras/Rap
      exchange factor.
AB  - Ras proteins operate as molecular switches in signal transduction pathways
      downstream of tyrosine kinases and G-protein-coupled receptors. Ras is switched
      from the inactive GDP-bound state to the active GTP-bound state by guanine
      nucleotide exchange factors (GEFs). We report here the cloning and
      characterization of RasGRP2, a longer alternatively spliced form of the recently
      cloned RapGEF, CalDAG-GEFI. A unique feature of RasGRP2 is that it is targeted to
      the plasma membrane by a combination of N-terminal myristoylation and
      palmitoylation. In vivo, RasGRP2 selectively catalyzes nucleotide exchange on N-
      and Ki-Ras, but not Ha-Ras. RasGRP2 also catalyzes nucleotide exchange on Rap1,
      but this RapGEF activity is less potent than that associated with CalDAG-GEFI.
      The nucleotide exchange activity of RasGRP2 toward N-Ras is stimulated by
      diacylglycerol and inhibited by calcium. The effects of diacylglycerol and
      calcium are additive but are not accompanied by any detectable change in the
      subcellular localization of RasGRP2. In contrast, CalDAG-GEFI is localized
      predominantly to the cytosol and lacks Ras exchange activity in vivo. However,
      prolonged exposure to phorbol esters, or growth in serum, results in localization
      of CalDAG-GEFI to the cell membrane and restoration of Ras exchange activity.
      Expression of RasGRP2 or CalDAG-GEFI in NIH3T3 cells transfected with wild type N
      Ras results in an accelerated growth rate but not morphologic transformation.
      Thus, under appropriate growth conditions, CalDAG-GEFI and RasGRP2 are dual
      specificity Ras and Rap exchange factors.

PMID- 10918069
TI  - Novel expression of equivocal messages containing both regions of
      choline/ethanolamine kinase and muscle type carnitine palmitoyltransferase I.
AB  - For characterization of the detailed gene structure of human muscle type
      carnitine palmitoyltransferase I (M-CPTI), we analyzed the 5'-upstream region of
      the M-CPTI transcripts. As a result, we found a cDNA clone containing a
      nucleotide sequence unexpected from the reported M-CPTI gene structure in the
      upstream region of its 5' end. Comparison of this nucleotide sequence with that
      of genomic DNA showed that this sequence was derived from the 3'-untranslated
      region of the gene encoding choline/ethanolamine kinase-beta (CK/EK-beta) located
      upstream of the M-CPTI gene. Southern blot analysis showed that there was no
      other region homologous to the CK/EK-beta gene in the whole human genome. Thus,
      the overlapping transcript was concluded to be produced from the functional genes
      of CK/EK-beta and M-CPTI. Furthermore, cDNAs containing both exons of these genes
      were detected by the polymerase chain reaction using the cDNA of human heart M
      CPTI obtained by specific reverse transcription from its 3'-untranslated region
      as a template. From these results, the production and organization of these
      overlapping transcripts are discussed.

PMID- 10918070
TI  - ABCA1 is the cAMP-inducible apolipoprotein receptor that mediates cholesterol
      secretion from macrophages.
AB  - Lipid-poor high density lipoprotein apolipoproteins remove cholesterol and
      phospholipids from cells by an active secretory pathway controlled by an ABC
      transporter called ABCA1. This pathway is induced by cholesterol and cAMP analogs
      in a cell-specific manner. Here we provide evidence that increased plasma
      membrane ABCA1 accounts for the enhanced apolipoprotein-mediated lipid secretion
      from macrophages induced by cAMP analogs. Treatment of RAW264 macrophages with 8
      bromo-cAMP caused parallel increases in apoA-I-mediated cholesterol efflux, ABCA1
      mRNA and protein levels, incorporation of ABCA1 into the plasma membrane, and
      binding of apoA-I to cell-surface ABCA1. All of these parameters declined to near
      base-line values within 6 h after removal of 8-bromo-cAMP, indicating that ABCA1
      is highly unstable and is degraded rapidly in the absence of inducer. Thus, ABCA1
      is likely to be the cAMP-inducible apolipoprotein receptor that promotes removal
      of cholesterol and phospholipids from macrophages.

PMID- 10918073
TI  - Full oncogenic activities of v-Src are mediated by multiple signaling pathways.
      Ras as an essential mediator for cell survival.
AB  - Tyrosine kinase oncoproteins cause simultaneous activation of multiple
      intracellular signaling pathways. However, the precise mechanisms by which
      individual pathways induce oncogenesis are not well understood. We have
      investigated the roles of individual signaling pathways in v-Src-dependent cell
      growth and survival by inhibiting one particular pathway. v-Src induced
      constitutive activation of signal transducers and activators of transcription 3
      (STAT3), phosphatidylinositol 3-kinase, and Ras in murine Ba/F3 cells and led to
      factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and
      phosphatidylinositol 3-kinase (Deltap85) inhibited v-Src-dependent growth by
      approximately 60 and approximately 40%, respectively. Moreover, dominant-negative
      Ras (N17) induced severe apoptosis, which was accompanied by down-regulation of
      Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase
      3 inhibitors remained viable even when N17 was expressed, the growth was reduced
      by approximately 85%. During N17- and STAT3D-induced growth suppression,
      expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17,
      whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D. Thus, v
      Src-activated Ras and STAT3 are involved in distinct but partly overlapping
      transcriptional regulation of cell cycle regulatory molecules. These results
      suggest that the full oncogenic activity of v-Src requires simultaneous
      activation of multiple signalings, in which Ras is particularly required for
      survival.

PMID- 10918074
TI  - A novel background potassium channel in rat atrial cells.
AB  - A K+ channel activated by intracellular ATP has been observed in inside-out
      patches from rat atrial cells. The channel has a slope conductance of 130 +/- 5
      pS in symmetrical 140 mM K+ solution, and is almost independent of voltage over
      the range from -80 to +80 mV. There is no detectable inactivation during
      application of ATP over a few minutes. In the presence of 3 mM intracellular ATP,
      channel openings occur as bursts with a mean open time of 1.7 ms, a mean closed
      time of 0.4 ms, a mean burst duration of 18 ms and a mean burst interval of 41
      ms. Kinetic analysis suggests that ATP mainly affects the burst duration and the
      burst interval of the channel. Based on the properties above, the channel differs
      from other known K+ channels in cardiac cells and may contribute to background K+
      current.

PMID- 10918072
TI  - MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several
      cytotoxic drugs and directly interacts with drugs as judged by interference with
      nucleotide trapping.
AB  - The human MDR3 gene is a member of the multidrug resistance (MDR) gene family.
      The MDR3 P-glycoprotein is a transmembrane protein that translocates
      phosphatidylcholine. The MDR1 P-glycoprotein related transports cytotoxic drugs.
      Its overexpression can make cells resistant to a variety of drugs. Attempts to
      show that MDR3 P-glycoprotein can cause MDR have been unsuccessful thus far.
      Here, we report an increased directional transport of several MDR1 P-glycoprotein
      substrates, such as digoxin, paclitaxel, and vinblastine, through polarized
      monolayers of MDR3-transfected cells. Transport of other good MDR1 P-glycoprotein
      substrates, including cyclosporin A and dexamethasone, was not detectably
      increased. MDR3 P-glycoprotein-dependent transport of a short-chain
      phosphatidylcholine analog and drugs was inhibited by several MDR reversal agents
      and other drugs, indicating an interaction between these compounds and MDR3 P-gp.
      Insect cell membranes from Sf9 cells overexpressing MDR3 showed specific MgATP
      binding and a vanadate-dependent, N-ethylmaleimide-sensitive nucleotide trapping
      activity, visualized by covalent binding with [alpha-(32)P]8-azido-ATP.
      Nucleotide trapping was (nearly) abolished by paclitaxel, vinblastine, and the
      MDR reversal agents verapamil, cyclosporin A, and PSC 833. We conclude that MDR3
      P-glycoprotein can bind and transport a subset of MDR1 P-glycoprotein substrates.
      The rate of MDR3 P-glycoprotein-mediated transport is low for most drugs,
      explaining why this protein is not detectably involved in multidrug resistance.
      It remains possible, however, that drug binding to MDR3 P-glycoprotein could
      adversely affect phospholipid or toxin secretion under conditions of stress (e.g.
      in pregnant heterozygotes with one MDR3 null allele).

PMID- 10918075
TI  - Epidermal growth factor regulates amino acid transport in chick embryo
      hepatocytes via protein kinase C.
AB  - System A-mediated amino acid transport, activation of different steps of signal
      transduction and involvement of different isoforms of protein kinase C (PKC) have
      been investigated in chick embryo hepatocytes after epidermal growth factor (EGF)
      stimulation. EGF rapidly (10 min) increased the rate of aminoisobutyric acid
      (AIB) uptake in chick embryo hepatocytes freshly isolated on the 19th day of
      embryonic life, while no change was detectable at other embryonal stages. The
      growth factor stimulation was abolished by PKC and tyrosine kinase inhibitors and
      was mimicked by 4-phorbol-12-myristate-13-acetate, dimethyl-2 (PMA). EGF
      treatment did not modify the phosphorylation of the isoform of phospholipase C
      (PLC-), and inositol trisphosphate (IP3) and intracellular calcium levels, but it
      induced an increase in PKC activity. Our data show that EGF regulates amino acid
      uptake, via PKC and without PLC- activation, only in the last period of chick
      embryo hepatocyte development. The effects of growth factor on PKC activity
      suggest the involvement of PKC- and - isoforms in EGF modulation of amino acid
      transport.

PMID- 10918076
TI  - Effects of resalination on intestinal glucose transport in chickens adapted to
      low Na+ intakes.
AB  - In chickens, we have shown that intestinal absorption of glucose via apical SGLT1
      and basolateral GLUT2 transport systems is affected by dietary Na+; low-Na+
      adapted birds show a dramatic reduction of glucose transporters in both membranes
      in the rectum, an intermediate response in the ileum and no effects in the
      jejunum. We have now studied the effect of resalination of low-Na+ adapted
      chickens on glucose kinetics across SGLT1 (using -methyl-D-glucoside as
      substrate) and GLUT2 (using D-glucose) and on the specific binding of phlorizin
      and cytochalasin B, respectively. Twelve-week-old male Leghorn chickens were fed
      wheat and barley with drinking water containing either 150 mM NaCl (high-Na+
      group) or 0. 015 mM (low-Na+ group) for 14 days (serum aldosterone: 242 +/- 6 pg
      ml-1 in the low-Na+ and 46 +/- 4 pg ml-1 in the high-Na+ group). On day 14, the
      low-Na+ group was either resalinated with an oral dose of NaCl (9 g (kg body wt)
      1) or switched to the high-Na+ condition, for 1 week. Serum aldosterone measured
      4 h, 1 day and 7 days after the change in NaCl intake fell to between 30 and 39
      pg ml-1. The changes in apical -methyl-D-glucoside and basolateral D-glucose
      transport observed in the ileum and rectum of low-Na+ adapted animals were
      completely reversed by resalination within 4 h of NaCl administration to the
      level of values observed for high-Na+ adapted birds. The good correlation between
      the -methyl-D-glucoside and D-glucose Vmax and the SGLT1 and GLUT2 density,
      respectively, supports the view that the increase in apical and basolateral
      hexose transport found in the ileum and rectum of both groups of resalinated
      birds is due to an increase in the number of protein transporters. The rapid
      changes in the number of glucose transporters observed suggest that the target of
      the regulatory signal(s) involved are the mature enterocytes present in the villi
      rather than the developing enterocytes in the crypt.

PMID- 10918077
TI  - Influence of the extent of haemoglobin hydrolysis on the digestive absorption of
      haem iron in the rat. An in vitro study.
AB  - This study was designed to assess the haem-peptide interactions which occur
      during progressive haemoglobin hydrolysis by digestive enzymes and their
      relationship with haem iron digestive absorption. The behaviour of different
      haemoglobin hydrolysates was studied using the Ussing chamber model. Hydrolysates
      were produced from enzyme digestion of bovine haemoglobin at pH 3 by pepsin and
      at pH 10 by subtilisin. Samples with increasing degrees of hydrolysis (0-15 %)
      were studied. Biochemical assays (pyridine haemochromogen method and UV
      absorption spectra) were used to follow haem solubility and haem-peptide
      interactions in samples. Increasing the hydrolysis level of haemoglobin was
      associated with an enhanced iron uptake; the highest uptake rate was reached
      between 8 and 11 % of globin hydrolysis, whichever enzyme was used. The
      mechanisms rendering iron soluble and available differ between the two enzymes.
      The comparison between biochemical and absorption data suggests that the
      formation of soluble peptide-haem complexes was not sufficient to enhance haem
      iron absorption, since globin-bound iron is poorly absorbed; an efficient
      absorption occurred only when haem was loosely bound to low molecular weight
      peptides.

PMID- 10918078
TI  - Cyclic AMP-mediated inhibition of noradrenaline-induced contraction and Ca2+
      influx in guinea-pig vas deferens.
AB  - The relaxation effects of forskolin and methylxanthines on noradrenaline (NA)
      induced contractions were investigated by measuring isotonic contraction and
      intracellular calcium concentration ([Ca2+]i) in the epididymal side of guinea
      pig vas deferens. NA (100 microM) and high K+ (55 mM) induced a biphasic
      contraction; fast, transient (phasic) and slow, sustained (tonic) phases. Both
      phases in either NA or high K+ stimulation were abolished in Ca2+-free solution.
      Pretreatment with 10 microM nifedipine, an L-type Ca2+ channel blocker, reduced
      both phasic and tonic contractions induced by high K+. In the case of NA-induced
      contraction, however, nifedipine reduced the phasic contraction but not the tonic
      contraction. The nifedipine-insensitive tonic contraction was relaxed by the
      application of polyvalent cations (Mn2+, Co2+, Cd2+ and La3+). These findings
      indicate that NA-induced biphasic contraction is mainly due to nifedipine
      insensitive Ca2+ influx, especially in the tonic phase. Cyclic AMP-increasing
      agents such as forskolin (0.5-10 microM), IBMX (5-500 microM) and caffeine (1-20
      mM) relaxed the NA-induced contraction extensively in a concentration-dependent
      manner. However, these agents only partially relaxed the high K+-induced
      contraction. Forskolin (10 microM) and IBMX (100 microM) reduced the [Ca2+]i
      response to NA, but had no effect on the [Ca2+]i response to high K+. These
      results suggest that an increase in intracellular cAMP may relax the NA-induced
      contraction by attenuating a nifedipine-insensitive Ca2+ influx and by a
      mechanism independent of a reduction in [Ca2+]i.

PMID- 10918079
TI  - Nitric oxide, cGMP and cAMP modulate nitrobenzylthioinosine-sensitive adenosine
      transport in human umbilical artery smooth muscle cells from subjects with
      gestational diabetes.
AB  - Adenosine transport was characterized in human umbilical artery smooth muscle
      cells isolated from non-diabetic and diabetic pregnant subjects. Transport of
      adenosine was mediated by a Na+-independent transport system inhibited by
      nanomolar concentrations of nitrobenzylthioinosine (NBMPR) in both cell types.
      Diabetes increased adenosine transport, an effect that was associated with a
      higher maximal velocity (Vmax) for NBMPR-sensitive (es) saturable nucleoside
      transport (18 +/- 2 vs. 61 +/- 3 pmol (microgram protein)-1 min-1, P < 0.05) and
      the maximal number of binding sites (Bmax) for specific [3H]NBMPR binding (74 +/-
      4 vs. 156 +/- 10 pmol (microgram protein)-1, P < 0.05), with no significant
      changes in the Michaelis-Menten (Km) and dissociation (Kd) constants,
      respectively. Adenosine transport was unaltered by inhibition of nitric oxide
      (NO) synthase (with 100 microM NG-nitro-L-arginine methyl ester, L-NAME) or
      protein synthesis (with 1 microM cycloheximide), but was increased by inhibition
      of adenylyl cyclase activity (with 100 microM, SQ-22536) in non-diabetic cells.
      Diabetes-induced adenosine transport was blocked by L-NAME and associated with an
      increase in L-[3H]citrulline formation from L-[3H]arginine and intracellular
      cGMP, but with a decrease in intracellular cAMP compared with non-diabetic cells.
      Expression of inducible NO synthase (iNOS) was unaltered by diabetes. Dibutyryl
      cGMP (dbcGMP) increased, but dibutyryl cAMP (dbcAMP) decreased, adenosine
      transport in non-diabetic cells. dbcGMP or the NO donor S
      nitrosoacetylpenicillamine (SNAP, 100 microM) did not alter the diabetes-elevated
      adenosine transport. However, activation of adenylyl cyclase with forskolin (1
      microM), directly or after incubation of cells with dbcAMP, inhibited adenosine
      transport in both cell types. Our findings provide the first evidence that
      adenosine transport in human umbilical artery smooth muscle cells is mediated by
      the NBMPR-sensitive transport system es, and that its activity is upregulated by
      gestational diabetes.

PMID- 10918080
TI  - Reflex responses from the main pulmonary artery and bifurcation in anaesthetised
      dogs.
AB  - This study was undertaken to determine the reflex cardiovascular and respiratory
      responses to discrete stimulation of pulmonary arterial baroreceptors using a
      preparation in which secondary modulation of responses from other reflexes was
      prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the
      chests widely opened and a cardiopulmonary bypass established. The main pulmonary
      arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar
      arteries on each side were vascularly isolated and perfused through the left
      pulmonary artery and drained via the right artery through a Starling resistance
      which controlled pulmonary arterial pressure. Pressures distending systemic
      baroreceptors and reflexogenic regions in the heart were controlled. Reflex
      vascular responses were assessed from changes in perfusion pressures to a
      vascularly isolated hind limb and to the remainder of the subdiaphragmatic
      systemic circulation, both of which were perfused at constant flows. Respiratory
      responses were assessed from recordings of efferent phrenic nerve activity.
      Increases in pulmonary arterial pressure consistently evoked increases in both
      perfusion pressures and in phrenic nerve activity. Both vascular and respiratory
      responses were obtained when pulmonary arterial pressure was increased to above
      about 30 mmHg. Responses increased at higher levels of pulmonary arterial
      pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg
      increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162
      +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence
      the vascular response to changes in pulmonary arterial pressure. The presence of
      a negative intrathoracic pressure of -20 mmHg resulted in larger vascular
      responses being obtained at lower levels of pulmonary arterial pressure. This
      indicates that the reflex may be more effective in the intact closed-chest
      animal. These results demonstrate that stimulation of pulmonary arterial
      baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex
      is likely to be elicited in circumstances where pulmonary arterial pressure
      increases and the negative excursions of intrathoracic pressure become greater.
      They are likely, therefore, to be involved in the cardio-respiratory response to
      exercise as well as in pathological states such as pulmonary hypertension or
      restrictive or obstructive lung disease.

PMID- 10918081
TI  - Absence of reflex vascular responses from the intrapulmonary circulation in
      anaesthetised dogs.
AB  - The aim of this investigation was to determine whether reflex cardiovascular
      responses were obtained to localised distension of the intrapulmonary arterial
      and venous circulations in a preparation in which the stimuli to other major
      reflexogenic areas were controlled and the lung was shown to possess reflex
      activity. Dogs were anaesthetised with -chloralose, artificially ventilated, the
      chests widely opened and a cardiopulmonary bypass established. The intrapulmonary
      region of the left lung was isolated and perfused through the left pulmonary
      artery and drained through cannulae in the left pulmonary veins via a Starling
      resistance. Intrapulmonary arterial and venous pressures were controlled by the
      rate of inflow of blood and the pressure applied to the Starling resistance.
      Pressures to the carotid, aortic and coronary baroreceptors and heart chambers
      were controlled. Responses of vascular resistance were assessed from changes in
      perfusion pressures to a vascularly isolated hind limb and to the remainder of
      the subdiaphragmatic circulation (flows constant). The reactivity of the
      preparation was demonstrated by observing decreases in vascular resistance to
      large step changes in carotid sinus pressure (systemic vascular resistance
      decreased by -40 +/- 5%), chemical stimulation of lung receptors by injection
      into the pulmonary circulation of veratridine or capsaicin (resistance decreased
      by -32 +/- 4%) and, in the four dogs tested, increasing pulmonary stroke volume
      to 450 ml (resistance decreased by -24 +/- 6%). However, despite this evidence
      that the lung was innervated, increases in intrapulmonary arterial pressure from
      14 +/- 1 to 43 +/- 3 mmHg or in intrapulmonary venous pressure from 5 +/- 2 to 34
      +/- 2 mmHg or both did not result in any consistent changes in systemic or limb
      vascular resistances. In two animals tested, however, there were marked decreases
      in efferent phrenic nerve activity. These results indicate that increases in
      pressure confined to the intrapulmonary arterial and venous circulations do not
      cause consistent reflex vascular responses, even though the preparation was shown
      to be reflexly active and the lung was shown to be innervated.

PMID- 10918082
TI  - Doppler sonography to monitor flow in different cerebral arteries in the rabbit.
AB  - Most of the transcranial Doppler (TCD) experimental studies on cerebral
      haemodynamics have been performed in the rabbit because of the similarity between
      its Willis circle and that of the human, but these studies have mainly been
      limited to the basilar artery. The present study was aimed at extending the use
      of TCD sonography to all other large cerebral arteries. In anaesthetised rabbits,
      these arteries were insonated from three different recording sites, i.e. top
      cranial, suboccipital and orbital, using a two-channel pulsed Doppler device
      equipped with 4 and 8 MHz probes. First, discrimination between intra- and
      extracranial arteries was achieved through a standard 'rebreathing' test
      (hypercapnic-hypoxic stimulation). The distinctive blood velocity response
      patterns, reflecting the different extents of metabolic reactivity in intra- and
      extracranial territories, are described and discussed. Intracranial arteries were
      then identified on the basis of their response to ipsi- and contralateral common
      carotid artery occlusion. This procedure allowed recording from the following
      arteries: anterior common trunk, anterior cerebral, internal carotid, middle
      cerebral and basilar; the latter could be simultaneously monitored with any of
      the others. This study provides an experimental model allowing investigation of
      regional differences in the haemodynamic response to neurogenic and
      pharmacological stimuli.

PMID- 10918083
TI  - Stretch reflexes in the rectus abdominis muscle in man.
AB  - The spinal reflex circuitry of the rectus abdominis (RA) muscle in man was
      investigated by the application of a mechanical tap to the muscle.
      Electromyographic recordings were made in ten healthy subjects, performing a
      series of manoeuvres, using pairs of surface electrodes placed bilaterally. The
      reflex responses elicited largely depended on the amount of tonic (postural)
      activity of the trunk. When standing in the upright position, no reflex activity
      was recorded in response to the tap. Reflex activity due to mechanical tap was
      readily recorded when the muscle became tonically active. Moderate, backward
      trunk extension introduced short-latency reflexes at 18.8 +/- 1.9 ms (mean +/-
      S.D.) ipsilaterally and 20.8 +/- 1.8 ms contralaterally. Excitatory reflex
      activity of longer latency was also recorded contralaterally in all subjects
      (latency 45.1 +/- 4.3 ms) and ipsilaterally in five of the ten subjects (latency
      47.2 +/- 2.6 ms). Vibration of the tapped muscle produced a reduction in the
      amplitude of the early reflex responses, whilst increasing the amplitude of the
      late responses. Moreover, the early reflexes were facilitated by the Jendrassik
      manoeuvre. Such observations are consistent with the early responses being
      mediated, at least partly, monosynaptically, and the late responses being of
      polysynaptic nature. This implies that muscle spindle afferents from rectus
      abdominis monosynaptically activate motoneurones contralaterally.

PMID- 10918084
TI  - Contractile properties, fatigue and recovery are not influenced by short-term
      creatine supplementation in human muscle.
AB  - There have been several studies on the effect of short-term creatine (Cr)
      supplementation on exercise performance, but none have investigated both
      voluntary and stimulated muscle contractions in the same experiment. Fourteen
      moderately active young men (19-28 years) were randomly assigned, in a double
      blind manner, to either a creatine (Cr) or placebo (P) group. The subjects
      supplemented their regular diet 4 times a day for 5 days with either 5 g Cr + 5 g
      maltodextrin (Cr group), or 5 g maltodextrin (P group). Isometric maximal
      voluntary contraction (MVC), muscle activation, as assessed using the modified
      twitch interpolation technique, electrically stimulated contractile properties,
      electromyography (EMG), endurance time and recovery from fatigue were measured in
      the elbow flexors. The fatigue protocol involved both voluntary and stimulated
      contractions. Following supplementation there was a significant weight gain in
      the Cr group (1.0 kg), whereas the P group did not change. For each group, pre
      supplementation measures were not significantly different from post
      supplementation for MVC, twitch and tetanic tensions at rest, time to peak
      tension, half-relaxation time and contraction duration. Prior to Cr
      supplementation time to fatigue was 10 +/- 4 min (mean +/- S.E.M.) for both
      groups, and following supplementation there was a non-significant increase of 1
      min in each group. MVC force, muscle activation, EMG, stimulated tensions and
      durations were similar for the Cr and P groups over the course of the fatigue
      protocol and did not change after supplementation. Furthermore, recovery of MVC,
      stimulated tensions and contractile speeds did not differ as a result of Cr
      supplementation. These results indicate that short-term Cr supplementation does
      not influence isometric elbow flexion force, muscle activation, stimulated
      contractile properties, or delay time to fatigue or improve recovery.

PMID- 10918085
TI  - A putative alternatively spliced variant of the P2X(1) purinoreceptor in human
      bladder.
AB  - Activation of purinergic P2X receptors, putatively P2X1, may be important in the
      initiation of contraction in human detrusor. Purinergic transmission may be more
      important in muscle taken from patients with bladder instability. In this study
      the presence of the P2X1 receptor subtype was confirmed using RT-PCR. In
      addition, the results indicate, at the mRNA level, the presence of a splice
      variant of P2X1 that is lacking part of the second transmembrane domain. It is
      therefore possible that human bladder expresses multiple isoforms of the P2X1
      receptor which may be potential sites for modifying or regulating putative
      purinergic activation of the human bladder.

PMID- 10918086
TI  - Human ejaculatory duct: parameters of smooth muscle motor activity and modulatory
      role of autonomic drugs.
AB  - The contractile behaviour and effects of several autonomic drugs on the motor
      activity of human isolated ejaculatory ducts were investigated. Ejaculatory ducts
      exhibited spontaneous contractions characterised by an amplitude of 2.35 +/- 0.28
      mN, a duration of 62. 9 +/- 3.72 s and a frequency of 0.64 +/- 0.014 waves min-1.
      Acetylcholine (10-5-10-4 m) induced a slight increase in basal tone and in the
      frequency of the contraction waves. These effects were suppressed by atropine (10
      4 m). Noradrenaline (norepinephrine) increased the basal tone and frequency of
      spontaneous contractions in a dose-dependent manner. These responses were
      competitively inhibited by HEAT, a selective a1-adrenoceptor antagonist. These
      preliminary functional findings, indicating the presence of spontaneous motor
      activity of human ejaculatory ducts and its possible control by adrenergic
      agonists, suggests a physiological role for human ejaculatory duct in the
      propulsion of semen from the seminal vesicle towards the urethra.

PMID- 10918087
TI  - [Pharmacoeconomics and antimicrobials].

PMID- 10918088
TI  - Clinical utility of in vitro antifungal susceptibility testing.
AB  - The incidence of fungal and yeast infections, especially Candida and Aspergillus,
      as well as other newer fungal infections has increased considerably in recent
      years. Treatment failures are due to microbiological or clinical resistance, the
      latter being related to the drug, host factors, the fungus and the therapeutic
      procedures. An overview of efforts to find correlations between microbiological
      and clinical resistance is presented. The NCCLS M27-A consensus document for in
      vitro susceptibility testing of Candida and Cryptococcus is a good attempt at
      this, as is the M38-P for some filamentous fungi. The data available thus far
      indicate that there is a relationship between in vitro resistance and clinical
      failure, but not between in vitro susceptibility and therapeutic success.
      Furthermore, the breakpoints (MIC) that can be applied to the susceptibility
      tests are established based more on the resistance limits than on susceptibility.
      MIC data are also essential to obtain distribution profiles of MIC values for
      fungal populations and for future correlations of MICs with clinical response.

PMID- 10918089
TI  - [Current state of multidrug resistance in tuberculosis].
AB  - Given the current concern about multiresistance to drugs in tuberculosis, the
      data from a large study in two different centers are presented. At the Hospital
      Universitario Reina Sofia de Cordoba 71,359 clinical isolates of Mycobacterium
      tuberculosis were processed and at the Centro de Referencia de Micobacterias
      2,350 cultures were studied. The percentage of total multiresistance at the
      Hospital Universitario was 6&#37; from 1996-1998, and 6.7&#37; at the Centro de
      Referencia in 1998. Although these figures are high, they are lower than in
      previous years and could indicate the beginning of a decreasing trend, following
      years of increasing in the 1990s.

PMID- 10918090
TI  - [Study of macrolide-resistant genes in group C and G streptococci].
AB  - In the present study we investigated the macrolide-lincosamide-streptogramin B
      (MLSB) resistance in 47 clinical isolates of group C beta-hemolytic streptococci
      and 17 group G streptococci. Resistance to erythromycin was found in 31.6%; and
      47%, respectively. On the basis of the erythromycin-clindamycin double-disk test,
      all strains were assigned to the MLSB phenotype. None of the strains were of the
      M phenotype. The distribution of the erythromycin-resistant genes were studied by
      dot blot hybridization and PCR. Resistance to erythromycin was due to the
      presence of mefA, ermB and ermTR genes. The ermTR gene was predominant among the
      group C and G streptococci (90% of the strains). Different mechanisms of
      erythromycin resistance predominate in group C and G streptococci than in
      Streptococcus pyogenes where there is an association between erythromycin
      resistance and active-efflux mechanism. Two of the strains harbored more than one
      erythromycin-resistant gene.

PMID- 10918091
TI  - [Accumulation and efflux of quinolones by clinical isolates of Stenotrophomonas
      maltophilia].
AB  - The presence of quinolone efflux pumps was analyzed in clinical isolates of
      Stenotrophomonas maltophilia. The presence of the protein Omp54, which is
      associated with the expression of multidrug resistant systems, was also tested.
      Western blot analysis of outer membrane proteins demonstrated that Omp54 was
      expressed in strains with high-level resistance to quinolones, whereas those
      strains with low MIC values did not express this protein. This result shows that
      Omp54 has an important role in the phenotype of quinolone resistance in clinical
      S. maltophilia isolates. Biochemical analyses have shown that clinical S.
      maltophilia strains are capable of quinolone efflux (namely norfloxacin,
      ofloxacin and ciprofloxacin). Quinolone efflux is dependent on the integrity of
      membrane potential. These data indicate the presence of active quinolone efflux
      pump systems in clinical S. maltophilia isolates.

PMID- 10918092
TI  - [Susceptibility to antimicrobial drugs used in the prophylaxis of meningococcal
      disease: situation after an epidemic wave].
AB  - In the early 1990s a rise in the incidence of meningococcal disease was observed
      in Galicia, Spain, most cases of which were caused by serogroup C meningococcal
      strains. As part of the epidemiological analysis of this epidemic wave, two
      studies of asymptomatic carriers of neisseria meningitidis were carried out: the
      first took place during the period of maximum incidence and coincided with a
      massive immunization campaign (December 1996 to January 1997); and the second was
      conducted one year later (January 1998). A total of 1234 meningococcal strains
      were isolated in both studies (789 in the first and 445 in the second study) and
      the susceptibility to rifampin, ciprofloxacin, ceftriaxone and sulfadiazine was
      determined. The susceptibility to rifampin, ciprofloxacin and cetriaxone was high
      among the strains isolated in both studies. For sulfadiazine, the percentage of
      resistant strains was 92.6% for the first and 86.3% for the second study.

PMID- 10918093
TI  - [Risk factors and prognosis of nosocomial pneumonia due to gram-negative bacteria
      in a general hospital].
AB  - Nosocomial pneumonia due to Gram-negative bacteria is one of the most important
      infections because of its high frequency, morbidity and mortality. The objective
      of this study was to determine the risk factors and prognosis for nosocomial
      pneumonia caused by Gram-negative bacteria. A group of 50 patients with
      nosocomial pneumonia due to Gram-negative bacteria were studied in a prospective,
      consecutive manner and compared with another group of 50 patients with similar
      characteristics but without infection. The diagnostic criteria, acquisition,
      previous infections, prognosis of the underlying disease, the initial severity of
      the clinical situation, presence of complications, type and evolution of
      antibiotic treatment were adjusted according to the criteria in the literature.
      Univariate and multivariate statistical analysis of the results was carried out.
      The risk factors found included the following: male sex, high-risk hospital
      units, nosocomial acquisition and previous manipulation with intubation and
      mechanical ventilation, previous pulmonary infections, and the use of wide
      spectrum antibiotics in the six weeks prior to the study. The most isolated Gram
      negative bacterium was Pseudomonas aeruginosa (32%), followed by polymicrobial
      flora (18%). Bacteriemia was found in 30% of the cases. Mortality was 24%, with
      the factors significantly associated with a poor prognosis being a serious
      underlying disease, a clinically critical situation, previous surgery,
      complications, Gram-negative bacteria, use of wide-spectrum antibiotics in the
      six months before the study, and advanced age. The mortality of the group was 8%.
      It was concluded that knowledge of the risk factors and prognosis of nosocomial
      pneumonia due to Gram-negative bacteria is of high importance to improve
      treatment and decrease morbidity and mortality.

PMID- 10918094
TI  - [Cost of antibiotic therapy in neutropenic patients undergoing peripheral blood
      stem cell transplantation for breast cancer].
AB  - The increase in pharmaceutical costs, especially for expensive procedures such as
      bone marrow transplants, has led to the study of the economic impact of febrile
      neutropenia in peripheral blood stem cell transplantation (PBSCT). We analyzed 89
      consecutive patients with breast cancer who underwent PBSCT. All patients
      developed febrile neutropenia and were administered an empirical intravenous
      regimen based on the combination of piperacillin-tazobactam and amikacin. We
      analyzed the direct costs of this treatment and grouped them into drug
      acquisition cost, administration costs (cost of the additional material), and
      preparation costs (time employed for the preparation and administration of the
      drug). We found that the overall cost was $1,110, 65% of which corresponded to
      the initial therapy and the rest (35%) to the use of additional antibiotics. This
      higher cost was especially related to the use of vancomycin or teicoplanin (50%).
      The acquisition costs accounted for 90% of the overall treatment costs. Thirty
      six patients (40%) did not need additional antibiotics and the cost in this group
      was less ($663). We concluded that knowledge of the costs of pharmacological
      therapy for infection in PBSCT is indispensable for the appropriate development
      of treatment units, especially in terms of optimizing resources and comparing
      different therapeutic or prophylactic approaches.

PMID- 10918095
TI  - [Treatment of respiratory infections: past, present, and future].

PMID- 10918096
TI  - [Consensus statement on surgical chemoprophylaxis].

PMID- 10918097
TI  - [Fournier's gangrene. A study of 12 patients and a review].
AB  - We present the clinicoepidemiological and therapeutic characteristics of 12
      patients with Fournier's gangrene. The mean age of the patients was 66 years and
      all had a known predisposing factor for the disease. In all cases there was a
      predominance of mixed flora (four Gram-positive cocci, nine Gram-negative bacilli
      and ten anaerobic pathogens), with only one case of bacteremia reported. Initial
      surgery was conducted and was complemented by antimicrobial administration
      (imipenem, cefotaxime, clindamycin, penicillin and gentamicin alone and in
      combination) and local treatment with sugar and povidone-iodine. Hyperbaric
      oxygen was not used in any cases. At the end of treatment a mesh graft could be
      applied in 11 patients, all of whom showed an excellent functional and aesthetic
      recovery. The mean time of hospital stay was lengthy (49 days). The good
      evolution of the lesions after starting the local treatments with the sugar
      povidone-iodine combination should be emphasized.

PMID- 10918098
TI  - Prochlorperazine versus promethazine for uncomplicated nausea and vomiting in the
      emergency department: a randomized, double-blind clinical trial.
AB  - STUDY OBJECTIVE: Nausea and vomiting related to gastritis or gastroenteritis are
      common complaints in the emergency department. The most effective antiemetic
      agent is yet undetermined. This study was conducted to compare the efficacy of
      prochlorperazine versus promethazine for uncomplicated nausea and vomiting in the
      ED. METHODS: The study was a randomized, double-blind comparison of
      prochlorperazine (Compazine) and promethazine (Phenergan) for acute ED treatment
      of gastritis or gastroenteritis. We studied patients 18 years or older with
      presumed uncomplicated gastritis or gastroenteritis who presented to 2 academic
      EDs. Patients were randomly assigned to receive either prochlorperazine, 10 mg
      intravenously, or promethazine, 25 mg intravenously. Visual analog scale readings
      of patient comfort were obtained at baseline and at 30- and 60-minute intervals.
      The primary endpoint was degree of relief at 30 and 60 minutes. Secondary
      endpoints were time to complete relief, need for further antiemetic medication
      (treatment failures), and side effects. Statistical analysis was performed using
      the Mann-Whitney U test for nonparametric analysis and repeated-measures analysis
      of variance (ANOVA). RESULTS: Eighty-four patients were enrolled in the study; 42
      received prochlorperazine and 42 received promethazine. There were no differences
      in demographics in the 2 groups. At baseline (time 0), there was no difference in
      symptoms (P =.23). At 30 and 60 minutes after receiving medication,
      prochlorperazine worked significantly better than promethazine (P =.004 and P
      <.001 using nonparametric analysis). Using repeated-measures ANOVA, there was a
      significant difference in symptoms over time for both groups (P <.001) and a
      significant difference in prochlorperazine versus promethazine (P =.002). Time to
      complete relief was significantly shorter with prochlorperazine (P =.021). There
      were significantly fewer treatment failures with prochlorperazine (P =.03, 9.5%
      versus 31%; difference 21%, 95% confidence interval 5 to 38). There was no
      difference in incidence of extrapyramidal effects. Prochlorperazine caused
      significantly fewer complaints of sleepiness (P =.002, 38% versus 71%; difference
      33%, 95% confidence interval 13 to 53; P =.002). CONCLUSION: Prochlorperazine
      works significantly better than promethazine for relieving symptoms of nausea and
      vomiting more quickly and completely in ED patients with uncomplicated nausea and
      vomiting.

PMID- 10918100
TI  - Serum levels of smooth muscle heavy-chain myosin in patients with ectopic
      pregnancy.
AB  - STUDY OBJECTIVE: Previous studies have suggested that serum markers of smooth
      muscle destruction have utility in predicting ectopic pregnancy. Our goal was to
      determine whether a novel marker of muscle destruction, smooth muscle heavy-chain
      myosin (SMHC), is elevated in the serum of patients with ectopic pregnancy.
      METHODS: We conducted a prospective cohort study, with consecutive enrollment, of
      all women in the first trimester of pregnancy who presented to our urban
      emergency department with complaints of lower abdominal pain with or without
      vaginal bleeding. Patients were excluded if there was a history of recent surgery
      or major trauma. Means were compared using 2-tailed Student's t test with P
      values less than.05 set for significance. Data analysis included calculation of
      receiver operating characteristic (ROC), 95% confidence intervals (CIs), and a
      regression model. RESULTS: A total of 175 patients were enrolled; ectopic
      pregnancy was diagnosed in 29, and 146 had other diagnoses. Patients with ectopic
      pregnancy had a mean serum SMHC concentration of 2.53 ng/dL (95% CI 1.84 to
      3.22), whereas those in the non-ectopic pregnancy group had a mean concentration
      of 1.41 ng/dL (95% CI 1.23 to 1.60; P <.0001). ROC analysis demonstrated an area
      under the curve of 0.72 (95% CI 0.65 to 0.79). Regression analysis to examine
      confounders in each group analyzed the effects of race, maternal age, estimated
      gestational age, and serum levels of human chorionic gonadotropin beta-subunit.
      Our analysis identified only a positive correlation between estimated gestational
      age and SMHC in the non-ectopic pregnancy group. CONCLUSION: There is a
      statistically significant elevation of serum SMHC levels in tubal pregnancy,
      although our data suggest that the assay has limited clinical utility as a lone
      marker for ectopic pregnancy. Further investigation is needed to determine
      whether the assay has a role as an adjunct in the evaluation of suspected ectopic
      pregnancy.

PMID- 10918099
TI  - Serum progesterone testing to predict ectopic pregnancy in symptomatic first
      trimester patients.
AB  - STUDY OBJECTIVE: This study was conducted to prospectively measure the accuracy
      of serum progesterone levels to detect ectopic pregnancy. METHODS: Seven hundred
      sixteen symptomatic first-trimester emergency department patients with abdominal
      pain or vaginal bleeding at a tertiary care military teaching hospital had
      progesterone levels measured by radioimmunoassay with results unavailable to the
      treating physician. All patients were monitored until a criterion standard
      diagnosis of intrauterine pregnancy or ectopic pregnancy was confirmed. RESULTS:
      A 14-month derivation phase (n=399) used receiver operating characteristic curve
      testing to select a cutoff value of progesterone less than 22 ng/mL. A 12-month
      validation phase (n=317) then retested this cutoff value. Combining both phases,
      there were 434 (61%) viable intrauterine pregnancies, 229 (32%) nonviable
      intrauterine pregnancies, and 52 (7. 3%) ectopic pregnancies, of which 17 were
      ruptured. Sensitivity, specificity, positive predictive values, and negative
      predictive values (95% confidence intervals) for progesterone levels less than 22
      ng/mL to detect ectopic pregnancy were 100% (94% to 100%), 27% (23% to 30%), 10%
      (7% to 12%), and 100% (98% to 100%), respectively. CONCLUSION: Given similar
      disease prevalence, roughly one fourth (178/716) of symptomatic patients can be
      classified as low risk (0%, 95% confidence interval 0 to 2%) for having an
      ectopic pregnancy using a progesterone cutoff of 22 ng/mL. Whether implementation
      of rapid progesterone testing can safely expedite care and reduce the need for
      urgent diagnostic evaluation or admission remains to be determined.

PMID- 10918101
TI  - Necessity of radiographs in the emergency department management of shoulder
      dislocations.
AB  - STUDY OBJECTIVE: To determine the necessity of radiographs in the emergency
      department management of patients with suspected shoulder dislocation. METHODS: A
      prospective, observational study was conducted at a university-affiliated, Level
      I trauma center ED with an emergency medicine residency program. Physicians
      entered all patients with a suspected shoulder dislocation and reported whether
      they were certain that the patient's shoulder was dislocated or reduced, before
      obtaining radiographs. Outcome measures were the assessments of joint position
      and the radiology reports of prereduction and postreduction films. RESULTS: One
      hundred four patients were enrolled in the study, including 98 with shoulder
      dislocations, and 191 physician assessments were performed (96 prereduction, 95
      postreduction). Twenty-eight patients had recurrent dislocations with an
      atraumatic mechanism (group 1), and 76 had no prior dislocation or a blunt
      mechanism of injury (group 2). There were no fractures in group 1 patients; the
      accuracy of confident assessments was 100% (95% confidence interval 92% to 100%).
      In group 2, the accuracy of confident assessments was 98% (95% confidence
      interval 94% to 100%). Incorrect assessments occurred only in patients with
      fractures. A derived algorithm would have reduced radiographs by 51%. CONCLUSION:
      Physicians are highly accurate in the clinical determination of shoulder
      dislocation and relocation. Radiographs should be obtained when the physician is
      uncertain of dislocation or reduction. Prereduction films should be obtained for
      patients with a blunt traumatic mechanism of injury, and postreduction for those
      found to have a fracture-dislocation. However, postreduction films add little in
      patients without fractures, and neither prereduction nor postreduction films are
      likely to affect the ED management of patients with recurrent dislocation by an
      atraumatic mechanism. Prospective validation of the derived algorithm is
      suggested.

PMID- 10918102
TI  - Toxicokinetics of ethylene glycol during fomepizole therapy: implications for
      management. For the Methylpyrazole for Toxic Alcohols Study Group.
AB  - STUDY OBJECTIVE: The elimination kinetics of ethylene glycol (EG) in human
      subjects treated with fomepizole (4-methylpyrazole) were analyzed to establish
      the efficacy of alcohol dehydrogenase (ADH) inhibition and to characterize
      elimination pathways. METHODS: Drug concentration data from patients enrolled in
      the EG arm of the Methylpyrazole for Toxic Alcohols trial, a prospective,
      multicenter, open-label trial of fomepizole, were analyzed and compared with
      published estimates. RESULTS: In 19 patients analyzed (EG concentrations of 3.5
      to 211 mg/dL), elimination was first order during fomepizole monotherapy (half
      life of 19.7+/-1.3 hours) and was not affected by the presence of ethanol. The
      elimination rate was significantly faster (half-life of <8.6+/-1.1 hours, P
      <.001) in the absence of fomepizole and ethanol. EG elimination by the kidneys
      was directly proportional to remaining renal function as estimated by creatinine
      clearance, with a fractional excretion of 25.5%+/-9.4%. Renal elimination and
      hemodialysis were the only significant routes of EG elimination as long as
      fomepizole concentrations were maintained well above 10 micromol/L (EG/fomepizole
      molar ratio, <100:1). All patients with normal serum creatinine concentrations at
      the initiation of fomepizole treatment had rapid rates of renal elimination (half
      life of 16.8+/-0.8 hours). CONCLUSION: At doses used, fomepizole effectively
      inhibits ADH-mediated metabolism of EG. Serum creatinine concentration at
      presentation and creatinine clearance can be used to predict EG elimination
      during fomepizole therapy and can help determine which patients will require
      hemodialysis to expedite EG elimination. An absolute EG concentration above 50
      mg/dL should no longer be used as an independent criterion for hemodialysis in
      patients treated with fomepizole.

PMID- 10918103
TI  - Combined evidence-based literature analysis and consensus guidelines for stocking
      of emergency antidotes in the United States.
AB  - STUDY OBJECTIVE: To develop guidelines for the stocking of antidotes at hospitals
      that accept emergency admissions using combined evidence-based and consensus
      methods. METHODS: Study participants were 12 medical care providers from
      disciplines that are affected by insufficient stocking of emergency antidotes
      (clinical pharmacology, critical care, clinical pharmacy, emergency medicine,
      hospital pharmacy, internal medicine, managed care pharmacy, clinical toxicology,
      pediatrics, poison control centers, pulmonary medicine, regulatory medicine).
      Selection of individuals for the study panel was based on evidence of previous
      antidote research or perspective regarding the purchase and use of antidotes. The
      literature regarding each antidote was systematically amassed using pre-1966
      literature files, current MEDLINE searches, the reference lists of major medical
      textbooks, and citations solicited from the consensus panel. Articles relevant to
      4 defined core questions were included. These articles formed the basis of an
      evidence-based analysis performed by the principal investigator. After literature
      analysis, a literature summary and proposed guidelines for antidote stocking were
      submitted to the panel. Consensus was formed by electronic iterative presentation
      of alternatives to each panel member using a modified Delphi method. All panel
      members participated in 5 rounds of guideline analysis of 20 antidotes. RESULTS:
      Of the 20 antidotes, 16 antidotes were ultimately recommended for stocking (N 
      acetylcysteine, atropine, Crotalid snake antivenin, calcium gluconate and
      chloride, cyanide antidote kit, deferoxamine, digoxin immune Fab, dimercaprol,
      ethanol, fomepizole, glucagon, methylene blue, naloxone, pralidoxime,
      physostigmine, sodium bicarbonate), 2 were not recommended for stocking (black
      widow antivenin, ethylenediamine tetraacetic acid), and consensus could not be
      reached for 2 antidotes (flumazenil, physostigmine). CONCLUSION: These guidelines
      provide a tool to be used in revising or creating policies and procedures with
      regard to the stocking of antidotes in hospitals that accept emergency patients.

PMID- 10918104
TI  - Octreotide: an antidote for sulfonylurea-induced hypoglycemia.
AB  - STUDY OBJECTIVES: Sulfonylurea agents are widely used as therapy for
      hyperglycemia in type 2 diabetes mellitus. In overdose, these agents can produce
      sustained and profound hypoglycemia that is refractory to treatment with dextrose
      alone. Our objective was to determine whether treatment with octreotide decreases
      glucose requirements and the number of hypoglycemic episodes in patients with
      sulfonylurea-induced hypoglycemia. METHODS: We retrospectively reviewed the
      charts of patients treated with octreotide for sulfonylurea-induced hypoglycemia
      from 1995 through 1998. The study took place in a large urban teaching hospital
      in the United States. We measured the number of episodes of hypoglycemia reported
      and the amount of dextrose used before and after treatment with octreotide. Using
      a failure time analysis, we compared the risk of hypoglycemia before and after
      octreotide administration. RESULTS: The age range of the 9 patients was 20 to 65
      years. Six patients ingested glyburide and 3 ingested glipizide. The number of
      hypoglycemic events recorded per patient before octreotide (mean 3.2) was greater
      than the number of hypoglycemic events recorded per patient after octreotide
      (mean 0.2, P =.008). Similarly, the number of ampules of 50% dextrose
      administered per patient before octreotide (mean 2.9) was greater than the number
      of ampules administered per patient after octreotide (0.2, P =.004). The risk of
      recurrent hypoglycemia before octreotide treatment was 27 times the risk of the
      group after octreotide treatment (P <.001). Stabilization of blood glucose
      concentration and cessation of rebound hypoglycemia occurred immediately after
      the administration of octreotide in all 9 patients. CONCLUSION: Octreotide
      appears to be safe and effective in preventing rebound hypoglycemia after
      sulfonylurea ingestion. Octreotide in combination with dextrose should be
      considered for first-line therapy in the treatment of sulfonylurea-induced
      hypoglycemia.

PMID- 10918105
TI  - Ethylene glycol toxicity: closing in on rational, evidence-based treatment.

PMID- 10918106
TI  - Human error in medicine: promise and pitfalls, part 2.

PMID- 10918107
TI  - Crisis at America's teaching hospitals.

PMID- 10918108
TI  - Evidence-based emergency medicine. The clinician and the medical literature: when
      can we take a shortcut?

PMID- 10918109
TI  - Brugada syndrome as the cause of syncope in a 49-year-old man.
AB  - We report the case of a 49-year-old man in whom a diagnosis of Brugada syndrome
      was made after he presented to the emergency department for evaluation of a
      syncopal episode. The diagnosis was made by ECG changes, after the characteristic
      findings of peculiar downsloping ST-segment elevation in leads V(1) and V(2) and
      QRS morphology resembling a right bundle branch block were identified. Emergency
      physician recognition of this syndrome and its ECG findings is essential, because
      without treatment the incidence of sudden cardiac death in these patients is
      high.

PMID- 10918110
TI  - Glyburide-ciprofloxacin interaction with resistant hypoglycemia.
AB  - Glyburide, a second-generation sulfonylurea hypoglycemic agent, is metabolized by
      the P-450 hepatic enzyme system. Ciprofloxacin, a widely used quinolone
      antibiotic, is a recognized P-450 enzyme inhibitor. Conflicting data exist in the
      medical literature on the ability of quinolone antibiotics to inhibit glyburide
      hepatic metabolism. We present a case of hypoglycemia and an elevated serum
      glyburide level after 1 week of ciprofloxacin use in a patient receiving long
      term glyburide therapy. Clinicians should consider this potential interaction in
      patients taking glyburide who require antibiotic therapy.

PMID- 10918111
TI  - Medical conditions and driver crash risk: do license restrictions affect public
      safety?

PMID- 10918112
TI  - Disease control and crash injury-modifying host risk factors.

PMID- 10918113
TI  - Letting go.

PMID- 10918114
TI  - Akathisia and prochlorperazine.

PMID- 10918116
TI  - Template charting systems.

PMID- 10918117
TI  - Telephone-assisted Heimlich maneuver.

PMID- 10918118
TI  - School bus safety

PMID- 10918119
TI  - Domestic violence: the role of EMS personnel

PMID- 10918120
TI  - Child abuse

PMID- 10918121
TI  - A view on the science: physical anthropology at the millennium
AB  - EDITOR'S NOTE The year 2000 marks the onset of the 21(st) century. In this
      transitional year, prominent physical anthropologists will provide brief
      reflections on our discipline, including what attracted them to it, and their
      views on the directions our discipline may pursue as we enter, in January 2001,
      the third millennium. Copyright 2000 Wiley-Liss, Inc.

PMID- 10918122
TI  - Biomechanics of mammalian feeding and primate evolution

PMID- 10918123
TI  - Mammalian feeding and primate evolution: An overview
AB  - Most of the papers included in this volume are derived from presentations in a
      symposium on Mammalian Feeding at the 65th Annual Meetings of the American
      Association of Physical Anthropologists in North Carolina in 1996. The aims of
      this symposium were to gather together the preeminent researchers on mammalian
      mastication and document the state of research in that field. The symposium
      emphasized in vivo studies of mammalian feeding because of a paucity of recent
      reviews of this field, but included morphometric and modeling papers as well.
      Subsequently the papers were revised, and were submitted in spring 1998 for
      publication, pending the outcome of peer review. Copyright 2000 Wiley-Liss, Inc.

PMID- 10918124
TI  - Electromyography of the anterior temporalis and masseter muscles of owl monkeys
      (Aotus trivirgatus) and the function of the postorbital septum.
AB  - Anthropoids and tarsiers are distinguished from all other vertebrates by the
      possession of a postorbital septum, which is formed by the frontal, alisphenoid,
      and zygomatic bones. Cartmill [(1980) In: Evolutionary Biology of the New World
      Monkeys and Continental Drift. New York: Plenum, p 243-274] suggested that the
      postorbital septum evolved in the stem lineage of tarsiers and anthropoids to
      insulate the eye from movements arising in the temporal fossa. Ross [(1996) Am J
      Phys Anthropol 91:305-324] suggested that the septum insulates the orbital
      contents from incursions by the line of action of the anterior temporal muscles
      caused by the unique combination of high degrees of orbital frontation and
      convergence. Both of these hypotheses must explain why insulation of the orbital
      contents could not be achieved by decreasing the size of the anterior temporal
      musculature with a corresponding increase in size of the remaining jaw adductors,
      rather than evolving a postorbital septum. One possibility is that the anterior
      temporalis is an important contributor to vertically directed bite forces during
      all biting and chewing activities. Another possibility is that reduction in
      anterior temporal musculature would compromise the ability to produce powerful
      bite forces, either at the incisors or along the postcanine toothrow. To evaluate
      these hypotheses, electromyographic (EMG) recordings were made from the masseter
      muscle and the anterior and posterior portions of the temporalis muscles of two
      owl monkeys, Aotus trivirgatus. The EMG data indicate that anterior temporalis
      activity relative to that of the superficial masseter is lower during incision
      than mastication. In addition, activity of the anterior temporalis is not
      consistently higher than the posterior temporalis during incision. The data
      indicate relatively greater activity of anterior temporalis compared to other
      muscles during isometric biting on the postcanine toothrow. This may be due to
      decreased activity in superficial masseter and posterior temporalis, rather than
      elevated anterior temporalis activity. The anterior temporalis is not
      consistently less variable in activity than the superficial masseter and
      posterior temporalis. The EMG data gathered here indicate no reason for
      suggesting that the anterior temporal muscles in anthropoids are utilized
      especially for incisal preparation of hard fruits. Maintenance of relatively high
      EMG activity in anterior temporalis across a wide range of biting behaviors is to
      be expected in a vertically oriented and rostrally positioned muscle such as this
      because, compared to the posterior temporalis, superficial masseter and medial
      pterygoid, it can contribute relatively larger vertical components of force to
      bites along the postcanine toothrow. The in vivo data do not support this
      hypothesis, possibly because of effects of bite point and bite force orientation.

PMID- 10918126
TI  - Evolution of anthropoid jaw loading and kinematic patterns.
AB  - Major transformations in the skull and masticatory system characterized the
      evolution of crown anthropoids. To offer further insight into the phylogenetic
      and arguably adaptive significance of specific primate mandibular loading and
      kinematic patterns, allometric analyses of metric parameters linked to
      masticatory function are performed within and between 47 strepsirhine and 45
      recent anthropoid species. When possible, basal anthropoids are considered. These
      results are subsequently integrated with prior experimental and morphological
      work on primate skull form. As compared to strepsirhines, crown anthropoids have
      a vertically longer ascending ramus linked to a glenoid and condyle positioned
      relatively higher above the occlusal plane. Interestingly, anthropoids and
      strepsirhines do not exhibit different mean ratios of condylar to glenoid height,
      which suggests that both clades are similar in their ability to evenly distribute
      occlusal contacts and perhaps forces along the postcanine teeth. Thus, given the
      considerable suborder differences in the scaling of both glenoid and condylar
      height, we argue that much of this variation in jaw-joint height is linked to
      suborder differences in relative facial height due in turn to increased
      encephalization, basicranial flexion, and facial kyphosis in anthropoids. Due to
      a more elongate ascending ramus, anthropoids evince more vertically oriented
      masseters than like-sized strepsirhines. Having a relatively longer ramus and a
      more medially displaced lateral pterygoid plate, crown anthropoids exhibit medial
      pterygoids oriented similar to those of strepsirhines, but with a variably longer
      lever arm. As anthropoid masseters are less advantageously placed to effect
      transverse movements/forces, we argue that balancing-side deep-masseter activity
      underlying a wishboning loading regime serves to increase, or at least maintain,
      transverse levels of jaw movement and occlusal force at the end of the
      masticatory power stroke. Crown anthropoids are also more isognathic and
      isodontic than strepsirhines. A consideration of early anthropoids suggests that
      the crown anthropoid masticatory pattern, i.e., more vertical masseters due to a
      high condyle as well as greater isognathy and isodonty, occurred stepwise during
      stem anthropoid evolution. This appears to correspond to a more transverse, and
      perhaps progressively larger, power stroke across oligopithecids, parapithecids,
      and propliopithecids.

PMID- 10918125
TI  - Symphyseal fusion and jaw-adductor muscle force: an EMG study.
AB  - The purpose of this study is to test various hypotheses about balancing-side jaw
      muscle recruitment patterns during mastication, with a major focus on testing the
      hypothesis that symphyseal fusion in anthropoids is due mainly to vertically-
      and/or transversely-directed jaw muscle forces. Furthermore, as the balancing
      side deep masseter has been shown to play an important role in wishboning of the
      macaque mandibular symphysis, we test the hypothesis that primates possessing a
      highly mobile mandibular symphysis do not exhibit the balancing-side deep
      masseter firing pattern that causes wishboning of the anthropoid mandible.
      Finally, we also test the hypothesis that balancing-side muscle recruitment
      patterns are importantly related to allometric constraints associated with the
      evolution of increasing body size. Electromyographic (EMG) activity of the left
      and right superficial and deep masseters were recorded and analyzed in baboons,
      macaques, owl monkeys, and thick-tailed galagos. The masseter was chosen for
      analysis because in the frontal projection its superficial portion exerts force
      primarily in the vertical (dorsoventral) direction, whereas its deep portion has
      a relatively larger component of force in the transverse direction. The
      symphyseal fusion-muscle recruitment hypothesis predicts that unlike anthropoids,
      galagos develop bite force with relatively little contribution from their
      balancing-side jaw muscles. Thus, compared to galagos, anthropoids recruit a
      larger percentage of force from their balancing-side muscles. If true, this means
      that during forceful mastication, galagos should have working-side/balancing-side
      (W/B) EMG ratios that are relatively large, whereas anthropoids should have W/B
      ratios that are relatively small. The EMG data indicate that galagos do indeed
      have the largest average W/B ratios for both the superficial and deep masseters
      (2.2 and 4.4, respectively). Among the anthropoids, the average W/B ratios for
      the superficial and deep masseters are 1.9 and 1.0 for baboons, 1.4 and 1.0 for
      macaques, and both values are 1.4 for owl monkeys. Of these ratios, however, the
      only significant difference between thick-tailed galagos and anthropoids are
      those associated with the deep masseter. Furthermore, the analysis of masseter
      firing patterns indicates that whereas baboons, macaques and owl monkeys exhibit
      the deep masseter firing pattern associated with wishboning of the macaque
      mandibular symphysis, galagos do not exhibit this firing pattern. The allometric
      constraint-muscle recruitment hypothesis predicts that larger primates must
      recruit relatively larger amounts of balancing-side muscle force so as to develop
      equivalent amounts of bite force. Operationally this means that during forceful
      mastication, the W/B EMG ratios for the superficial and deep masseters should be
      negatively correlated with body size. Our analysis clearly refutes this
      hypothesis. As already noted, the average W/B ratios for both the superficial and
      deep masseter are largest in thick-tailed galagos, and not, as predicted by the
      allometric constraint hypothesis, in owl monkeys, an anthropoid whose body size
      is smaller than that of thick-tailed galagos. Our analysis also indicates that
      owl monkeys have W/B ratios that are small and more similar to those of the much
      larger-sized baboons and macaques. Thus, both the analysis of the W/B EMG ratios
      and the muscle firing pattern data support the hypothesis that symphyseal fusion
      and transversely-directed muscle force in anthropoids are functionally linked.
      This in turn supports the hypothesis that the evolution of symphyseal fusion in
      anthropoids is an adaptation to strengthen the symphysis so as to counter
      increased wishboning stress during forceful unilateral mastication. (ABSTRACT
      TRUNCATED)

PMID- 10918127
TI  - Why fuse the mandibular symphysis? A comparative analysis.
AB  - Fused symphyses, which evolved independently in several mammalian taxa, including
      anthropoids, are stiffer and stronger than unfused symphyses. This paper tests
      the hypothesis that orientations of tooth movements during occlusion are the
      primary basis for variations in symphyseal fusion. Mammals whose teeth have
      primarily dorsally oriented occlusal trajectories and/or rotate their mandibles
      during occlusion will not benefit from symphyseal fusion because it prevents
      independent mandibular movements and because unfused symphyses transfer dorsally
      oriented forces with equal efficiency; mammals with predominantly transverse
      power strokes are predicted to benefit from symphyseal fusion or greatly
      restricted mediolateral movement at the symphysis in order to increase force
      transfer efficiency across the symphysis in the transverse plane. These
      hypotheses are tested with comparative data on symphyseal and occlusal morphology
      in several mammals, and with kinematic and EMG analyses of mastication in
      opossums (Didelphis virginiana) and goats (Capra hircus) that are compared with
      published data on chewing in primates. Among mammals, symphyseal fusion or a
      morphology that greatly restricts movement correlates significantly with occlusal
      orientation: species with more transversely oriented occlusal planes tend to have
      fused symphyses. The ratio of working- to balancing-side adductor muscle force in
      goats and opossums is close to 1:1, as in macaques, but goats and opossums have
      mandibles that rotate independently during occlusion, and have predominantly
      vertically oriented tooth movements during the power stroke. Symphyseal fusion is
      therefore most likely an adaptation for increasing the efficiency of transfer of
      transversely oriented occlusal forces in mammals whose mandibles do not rotate
      independently during the power stroke.

PMID- 10918128
TI  - Experimental observation, theoretical models, and biomechanical inference in the
      study of mandibular form.
AB  - Experimental studies and mathematical models are disparate approaches for
      inferring the stress and strain environment in mammalian jaws. Experimental
      designs offer accurate, although limited, characterization of biomechanical
      behavior, while mathematical approaches (finite element modeling in particular)
      offer unparalleled precision in depiction of strain magnitudes, directions, and
      gradients throughout the mandible. Because the empirical (experimental) and
      theoretical (mathematical) perspectives differ in their initial assumptions and
      their proximate goals, the two methods can yield divergent conclusions about how
      masticatory stresses are distributed in the dentary. These different sources of
      inference may, therefore, tangibly influence subsequent biological
      interpretation. In vitro observation of bone strain in primate mandibles under
      controlled loading conditions offers a test of finite element model predictions.
      Two issues which have been addressed by both finite element models and
      experimental approaches are: (1) the distribution of torsional shear strains in
      anthropoid jaws and (2) the dissipation of bite forces in the human alveolar
      process. Not surprisingly, the experimental data and mathematical models agree on
      some issues, but on others exhibit discordance. Achieving congruence between
      these methods is critical if the nature of the relationship of masticatory stress
      to mandibular form is to be intelligently assessed. A case study of
      functional/mechanical significance of gnathic morphology in the hominid genus
      Paranthropus offers insight into the potential benefit of combining theoretical
      and experimental approaches. Certain finite element analyses claim to have
      identified a biomechanical problem unrecognized in previous comparative work,
      which, in essence, is that the enlarged transverse dimensions of the postcanine
      corpus may have a less important role in resisting torsional stresses than
      previously thought. Experimental data have identified subperiosteal cortical
      thinning as a culprit in diminishing the role of cross-sectional geometry in
      conditioning the strain environment. These observations raise questions
      concerning the biomechanical significance of mandibular form in early hominids,
      fueling persistent arguments over whether gnathic morphology can be related to
      dietary specialization in the "robust" australopithecines. Nonmechanical
      explanations (e.g., tooth size or body size) for Paranthropus mandibular
      dimensions, however, are not compelling as competing hypotheses. Both theoretical
      and experimental models are in need of refinement before it is possible to
      conclude that the jaws of the "robust" australopithecines are not functionally
      linked to elevated masticatory loads.

PMID- 10918129
TI  - Elastic properties and masticatory bone stress in the macaque mandible.
AB  - One important limitation of mechanical analyses with strain gages is the
      difficulty in directly estimating patterns of stress or loading in skeletal
      elements from strain measurements. Because of the inherent anisotropy in cortical
      bone, orientation of principal strains and stresses do not necessarily coincide,
      and it has been demonstrated theoretically that such differences may be as great
      as 45 degrees (Cowin and Hart, 1990). Likewise, relative proportions of stress
      and strain magnitudes may differ. This investigation measured the elastic
      properties of a region of cortical bone on both the buccal and lingual surfaces
      of the lower border of the macaque mandible. The elastic property data was then
      combined with macaque mandibular strain data from published and a new in vivo
      strain gage experiment to determine directions and magnitudes of maximum and
      minimum principal stresses. The goal was to compare the stresses and strains and
      assess the differences in orientation and relative magnitude between them. The
      main question was whether these differences might lead to different
      interpretations of mandibular function. Elastic and shear moduli, and Poisson's
      ratios were measured using an ultrasonic technique from buccal and lingual
      cortical surfaces in 12 macaque mandibles. Mandibular strain gage data were taken
      from a published set of experiments (Hylander, 1979), and from a new experiment
      in which rosette strain gauges were fixed to the buccal and lingual cortices of
      the mandibular corpus of an adult female Macaca fascicularis, after which bone
      strain was recorded during mastication. Averaged elastic properties were combined
      with strain data to calculate an estimate of stresses in the mandibular corpus.
      The elastic properties were similar to those of the human mandibular cortex. Near
      its lower border, the macaque mandible was most stiff in a longitudinal
      direction, less stiff in an inferosuperior direction, and least stiff in a
      direction normal to the bone's surface. The lingual aspect of the mandible was
      slightly stiffer than the buccal aspect. Magnitudes of stresses calculated from
      average strains ranged from a compressive stress of -16.00 GPa to a tensile
      stress of 8.84 GPa. The orientation of the principal stresses depended on whether
      the strain gage site was on the working or balancing side. On the balancing side
      of the mandibles, maximum principal stresses were oriented nearly perpendicular
      to the lower border of the mandible. On the working side of the mandibles, the
      orientation of the maximum principal stresses was more variable than on the
      balancing side, indicating a larger range of possible mechanisms of loading. Near
      the lower border of the mandible, differences between the orientation of stresses
      and strains were 12 degrees or less. Compared to ratios between maximum and
      minimum strains, ratios between maximum and minimum stresses were more divergent
      from a ratio of 1.0. Results did not provide any major reinterpretations of
      mandibular function in macaques, but rather confirmed and extended existing work.
      The differences between stresses and strains on the balancing side of the
      mandible generally supported the view that during the power stroke the mandible
      was bent and slightly twisted both during mastication and transducer biting. The
      calculated stresses served to de-emphasize the relative importance of torsion. On
      the working side, the greater range of variability in the stress analysis
      compared to the strain analysis suggested that a more detailed examination of
      loadings and stress patterns in each individual experiment would be useful to
      interpret the results. Torsion was evident on the working side; but in a number
      of experiments, further information was needed to interpret other superimposed
      regional loading patterns, which may have included parasagittal bending and
      reverse parasagittal bending.

PMID- 10918130
TI  - Strain in the braincase and its sutures during function.
AB  - The skull is distinguished from other parts of the skeleton by its composite
      construction. The sutures between bony elements provide for interstitial growth
      of the cranium, but at the same time they alter the transmission of stress and
      strain through the skull. Strain gages were bonded to the frontal and parietal
      bones of miniature pigs and across the interfrontal, interparietal and coronal
      sutures. Strains were recorded 1) during natural mastication in conjunction with
      electromyographic activity from the jaw muscles and 2) during stimulation of
      various cranial muscles in anesthetized animals. Vault sutures exhibited vastly
      higher strains than did the adjoining bones. Further, bone strain primarily
      reflected torsion of the braincase set up by asymmetrical muscle contraction; the
      tensile axis alternated between +45 degrees and -45 degrees depending on which
      diagonal masseter/temporalis pair was most active. However, suture strains were
      not related to overall torsion but instead were responses to local muscle
      actions. Only the coronal suture showed significant strain (tension) during jaw
      opening; this was caused by the contraction of neck muscles. All sutures showed
      strain during jaw closing, but polarity depended on the pattern of muscle usage.
      For example, masseter contraction tensed the coronal suture and the anterior part
      of the interfrontal suture, whereas the temporalis caused compression in these
      locations. Peak tensile strains were larger than peak compressive strains.
      Histology suggested that the skull is bent at the sutures, with the ectocranial
      surface tensed and the endocranial surface predominantly compressed.
      Collectively, these results indicate that skulls with patent sutures should be
      analyzed as complexes of independent parts rather than solid structures.

PMID- 10918131
TI  - Ontogeny of histochemical fiber types and muscle function in the masseter muscle
      of miniature swine.
AB  - In this study of masticatory maturation, the ontogeny of the histochemical fiber
      type composition of musculus masseter is examined in the omnivorous miniature
      swine (Sus scrofa). Fiber type characteristics are interpreted by comparison with
      electromyography (EMG) recorded during feeding behavior. Similar to locomotion
      studies, the results suggest a correspondence between the composition and
      arrangement of motor units and their recruitment pattern. Serial sections of
      masseter muscles from 10 minipigs, ranging from 2 weeks to slightly over 1 year
      of age, were stained for myosin adenosine triphosphatase (mATPase) activity to
      distinguish slow-twitch from fast-twitch fibers, and for nicotinamide adenosine
      dehydrogenase-tetrazolium reductase to assess the aerobic capacity of the same
      fibers. Although maintaining a uniformly high aerobic capacity throughout
      ontogeny and in adult animals, a transition is observed in the relative
      proportions of fast- and slow-twitch fibers. The primarily fast-twitch neonatal
      pig masseter eventually comprises approximately 25-30% slow-twitch fibers in
      adults, with a higher predominance of slow fibers in the deep (vs. superficial)
      and anterior (vs. posterior) regions of the muscle. Furthermore, while individual
      fibers of adult masseters generally stain for either alkaline- or acid-stable
      mATPase activity, a substantial proportion of cells in developing animals
      exhibits the presence of both isozymes. EMG results indicate functional
      heterogeneity within the masseter of adult pigs. During chewing, when pig chow is
      replaced by cracked corn, EMG activity in the deep portion of the muscle either
      decreases or increases slightly. In the superficial portion, however, muscle
      amplitudes become dramatically higher for corn, surpassing levels generated for
      chewing the less obdurate chow. These results are consistent with a behavioral
      transition from neonatal suckling to sustained mastication of foods of more
      complex textures eaten by adult pigs. The relationship between these fiber type
      and EMG results for pig masseter corresponds to those pertaining to motor unit
      recruitment in the extensor muscles of locomotion. Implications of this work for
      the evolutionary morphology of mastication also are discussed.

PMID- 10918132
TI  - Regioselectivity of enzymatic glycosylation of 6-O-acyl glycosides in
      supersaturated solutions.
AB  - The regioselectivity of enzymatic transglycosylation of 6-O-acetyl glycosides in
      supersaturated solutions was investigated using a range of commercially available
      enzymes, Escherichia coli, barley, and Kluyveromyces spp. beta-galactosidase,
      green coffee bean alpha-galactosidase, jack bean alpha-mannosidase, rice alpha
      glucosidase, and almond beta-glucosidase. It has been shown that 6-O-acetyl
      glycosides serve as good substrates for these enzymes, which, under the reaction
      conditions, are "forced" to transfer monosaccharide units to the secondary
      hydroxyl groups of the acceptors. In a variety of transglycosylations studied the
      (1-3)-linked disaccharide products were the predominant regioisomers isolated.
      The selectivity of the reaction varied significantly depending on the acceptor
      glycosides and the enzyme used. Exquisite specificity was observed in some cases,
      but in others approximately equal quantities of two disaccharides products were
      isolated. In the best transfers the yield approached 30%. The methodology
      described offers a quick and facile route to disaccharides that may be difficult
      and/or time consuming to make by conventional chemical synthesis.

PMID- 10918133
TI  - Expression, immobilization, and enzymatic characterization of cellulose-binding
      domain-organophosphorus hydrolase fusion enzymes.
AB  - Bifunctional fusion proteins consisting of organophosphate hydrolase (OPH)
      moieties linked to a Clostridium-derived cellulose-binding domain (CBD) were
      shown to be highly effective in degrading organophosphate nerve agents, enabling
      purification and immobilization onto different cellulose materials in essentially
      a single step. Enzyme kinetics studies were performed for the CBD-OPH fusions
      using paraoxon as the substrate. The kinetics values of the unbound fusion
      enzymes were similar to OPH with a modest increase in K(m). Immobilization of the
      enzymes onto microcrystalline cellulose resulted in a further increase in the
      K(m) values of approximately twofold. The pH profile of the cellulose-immobilized
      enzymes was also only minimally affected. The CBD-OPH fusion proteins could be
      immobilized onto a variety of cellulose matrixes, and retained up to 85% of their
      original activity for 30 days. The durability of the bound fusions increased with
      the amount of Avicel used, suggesting that protein/cellulose interactions may
      have a dramatic stabilizing effect. Repeated hydrolysis of paraoxon was achieved
      in an immobilized enzyme reactor with 100% degradation efficiency over 45 days.
      These fusion proteins should prove to be invaluable tools for the development of
      low cost, OPH-based cellulose materials for the simultaneous adsorption and
      degradation of stored or spilled organophosphate wastes.

PMID- 10918134
TI  - Modeling solid-to-solid biocatalysis: integration of six consecutive steps.
AB  - A quantitative model for the conversion of a solid-substrate salt to a solid
      product salt in a batch bioreactor seeded with product crystals is presented. The
      overall process consists of six serial steps (with dissolution and
      crystallization each in themselves complex multistep processes): solid-salt
      dissolution, salt dissociation into an ionic substrate and a counter-ion,
      bioconversion accompanied by biocatalyst inactivation, complexation of the ionic
      product with the counter-ion, and salt crystal growth. In the model, the
      consecutive steps are integrated, including biocatalyst inactivation and assuming
      that salt dissociation and complexation of ions are at equilibrium. Model
      parameters were determined previously in separate independent experiments. To
      validate the model, either dissolved or solid Ca-maleate was converted to solid
      Ca-D-malate by permeabilized Pseudomonas pseudoalcaligenes in a batch bioreactor
      seeded with Ca-D-malate crystals. The model very well predicted the
      concentrations of all components in the liquid phase (Ca-maleate, Ca(2+),
      maleate(2-), D-malate(2-), and Ca-D-malate) and the amounts of the solid phases
      (Ca-maleate. H(2)O and Ca-D-malate. 3H(2)O), especially when high initial amounts
      of Ca-maleate. H(2)O and Ca-D-malate. 3H(2)O were present.

PMID- 10918135
TI  - Leukemia inhibitory factor (LIF) concentration modulates embryonic stem cell self
      renewal and differentiation independently of proliferation.
AB  - A major limitation of the widespread use of stem cells in a variety of
      biotechnological applications is the relatively low level of knowledge about how
      to maintain these cells in vitro without losing the long-term multilineage growth
      properties required for their clinical utility. An experimental and theoretical
      framework for predicting and controlling the outcome of stem cell stimulation by
      exogenous cytokines would thus be useful. An emerging theme from recent
      hematopoietic stem cell (HSC)-expansion studies is that a net gain in HSC numbers
      requires the maintenance of critical signaling ligand(s) above a threshold level.
      These ligand-receptor complex thresholds can be maintained, for example, by high
      concentrations of soluble cytokines or by cytokine presentation on cell surfaces.
      According to such a model, when the relevant ligand-receptor interaction falls
      below this threshold level, the probability of a differentiation response is
      increased; otherwise, self-renewal is favored. Taking advantage of the ability of
      the cytokine leukemia inhibitory factor (LIF) to maintain embryonic stem (ES)
      cell pluripotentiality at high concentrations, we are testing this model by
      investigating critical parameters in the control of ES cell responses. We have
      developed quantitative assays of ES cell differentiation by measuring cell
      surface alkaline phosphatase activity, cell-surface stage specific embryonic
      antigen (SSEA)-1 expression, and the ability of ES cells to form embryoid bodies.
      Examination of ES cell responses over a range of LIF concentrations shows that
      LIF supplementation has little effect on ES cell-growth rate but significantly
      alters the probability of a cell undergoing a self-renewal vs. a differentiation
      division. In vitro culture parameters such as inoculum cell density, medium
      exchange, as well as cell-intrinsic processes such as autocrine secretion are
      shown to affect this decision. In addition to yielding new information on stem
      cell regulation by exogenous factors, these studies provide important clues about
      culture of these cells and should stimulate further investigations into the
      mechanistic basis of stem cell differentiation control.

PMID- 10918136
TI  - Lysozyme extraction from egg white using reverse micelles in a Graesser
      contactor: mass transfer characterization.
AB  - The gentle mixing characteristics of a Graesser contactor can help to avoid the
      formation of stable emulsions, which is one advantage of this type of contactor
      when used with reversed micellar extraction. In this study, the performance of
      the Graesser contactor in lysozyme extraction from hen egg white is investigated.
      The concentration profile of lysozyme in the aqueous and organic phases indicated
      that, while substantial axial mixing occurred in the contactor, the extraction
      yield was in the range of 97% to 99%. The number of mass transfer units (N(ox))
      was determined using a diffusion model, and the influence of aqueous-to-organic
      phase flow ratio, rotor speed, and total throughput on contactor performance was
      studied. It was found that the diffusion model could describe quite well the
      extraction of lysozyme from hen egg white using reversed micelles. The optimal
      conditions for the extraction at steady state were found to be a rotor speed of 5
      rpm, an aqueous-to-organic phase flow ratio of 60:20 mL/min, and a total
      throughput of 80 mL/min. In addition, back-extraction was also performed using
      the conventional method (1.5 M KBr at pH 11.5) in the contactor. It was found
      that this mass transfer was not well described by a diffusion model, although 85%
      of the lysozyme could be recovered with the operating conditions used: a rotor
      speed of 10 rpm, and an aqueous-to-organic flow rate of 10:10 mL/min.

PMID- 10918137
TI  - Alcoholysis and reverse hydrolysis reactions in organic one-phase system with a
      hyperthermophilic beta-glycosidase.
AB  - Alcoholysis and reverse hydrolysis reactions were performed enzymatically in one
      phase water-saturated 1-heptanol systems. Lactose or glucose was used as
      substrate to produce heptyl-beta-galactoside and/or heptyl-beta-glucoside,
      respectively. When alcoholysis of lactose was performed at 37 degrees C with beta
      galactosidase from Escherichia coli, the initial rate was 14 nmol/mL min, and the
      limiting factors were the poor solubility of the substrate in 1-heptanol and low
      thermal stability of the enzyme. When a hyperthermophilic beta-glycosidase was
      used at 90 degrees C, the rate was 3.14-fold higher; in this case a higher
      concentration of soluble lactose in the water-saturated heptanol was available to
      the enzyme due to the higher temperature. The hyperthermophilic beta-glycosidase
      was also able to use glucose and galactose as substrates to achieve the reverse
      hydrolysis reaction. As a consequence, when lactose was used as substrate, heptyl
      beta-galactoside was formed by alcoholysis, while the released glucose moiety was
      used in a secondary reverse hydrolysis reaction to produce heptyl-beta-glucoside.
      Both reactions followed Michaelis-Menten kinetics behavior. Neither lactose nor
      heptyl glycosides were hydrolyzed by this enzyme in water-saturated heptanol.
      However, the conversion was limited by a strong product inhibition and the
      formation of oligosaccharides, especially at high substrate concentrations,
      reducing the final glycoside yield.

PMID- 10918138
TI  - Comparison of methods for thermolysin-catalyzed peptide synthesis including a
      novel more active catalyst.
AB  - This is a comparative study of the performance of thermolysin for enzymatic
      peptide synthesis by reversed hydrolysis in several different reaction systems. Z
      Gln-Leu-NH(2) was synthesized in acetonitrile containing 5% water (with various
      catalyst preparation methods) as well as by the "solid-to-solid" and frozen
      aqueous methods. Reaction rates (values in nanomoles per minute per milligram) in
      acetonitrile depended significantly on the method of addition of enzyme: (a)
      direct suspension in the reaction mixture as freeze-dried powders gave 60 to 95;
      (b) addition as an aqueous solution, so that enzyme precipitates on mixing with
      acetonitrile, gave 230; (c) addition as an aqueous suspension gave a remarkable
      increase in reaction rates (up to 780); (d) immobilized enzymes (adsorbed at
      saturating loading on celite, silica, Amberlite XAD-7, or polypropylene, then
      dried by propanol rinsing) all gave <230. It is postulated that, starting with
      the enzyme already in the form of solid particles in aqueous buffer, there is a
      minimum chance of alteration of its optimal conformation during transfer to the
      organic medium. For solid-to-solid synthesis with 10% water content we found
      initial rates of 670 under optimized conditions. In frozen aqueous synthesis,
      rates were <10. Equilibrium yields were always around 60% in low water organic
      solvent, whereas they were found to >80% in the aqueous systems studied.

PMID- 10918139
TI  - A diffusion model and optimal cell loading for immobilized cell biocatalysts.
AB  - A diffusion model based on the random pore model is derived for immobilized cell
      biocatalysts and verified with 19 sets of experimental diffusion data. The
      predicted effective diffusivity relative to that for the support matrix reflects
      a quadratic dependence on the cell loading and contains a single parameter that
      depends on the intracellular diffusivity and the chemical partitioning
      coefficient. The model is used to predict optimal cell loadings that maximize the
      total reaction rate in an immobilized cell biocatalyst. A rule of thumb based on
      the diffusion model is obtained to the effect that the cell loading should be at
      least (1/3) for single reactions regardless of the kinetics and diffusional
      resistances. A means of calculating improved lower bounds is provided for cases
      where the cellular diffusional resistance is known but the kinetics are not. The
      optimal cell loadings for reversible first-order and for Michaelis-Menten
      kinetics are presented and demonstrated to be within the range of conditions of
      practical interest.

PMID- 10918140
TI  - Experimental measurement of particle size distribution and voidage in an expanded
      bed adsorption system.
AB  - This paper presents an experimental analysis of matrix bead size distribution and
      voidage variations with axial height in an expanded bed adsorption system. Use of
      a specially constructed expanded bed with side ports has enabled sampling from
      within the expanded bed along the vertical axis. Particles removed from within
      the bed were measured for their size distributions. Residence time distribution
      studies were used to estimate bed voidage. Measurements of axial and radial
      particle size distributions and axial voidage distribution have been made at
      different flow rates. Particle size was found to be radially constant, indicating
      constant stratification in the column. The particle size was found to decrease
      with increasing axial height. Voidage increased with axial height from a settled
      bed value of 0.39 to approaching unity for high liquid velocities and increased
      at a constant axial position with increased flowrate. This information provides
      key insight into bed stability and data for the improved modeling of this
      important unit operation.

PMID- 10918141
TI  - Use of holographic laser interferometry to study the diffusion of polymers in
      gels.
AB  - The aim of this study was to demonstrate the potential for holographic
      interferometry to be used for diffusion studies of large molecules in gels. The
      diffusion and partitioning of BSA (67,000 g/mol) and pullulans (5,900-112,000
      g/mol) in agarose gel were investigated. The gel diffusion coefficients obtained
      for BSA were higher when distilled water was used as a solvent compared to those
      obtained with 0.1 M NaCl as the solvent. Furthermore, the gel diffusion
      coefficient increased with increasing BSA concentration. The same trend was found
      for liquid BSA diffusion coefficients obtained by DLS. BSA partition coefficients
      obtained at different agarose gel concentrations (2-6%, w/w) decreased slightly
      with increasing gel concentration. However, all BSA gel diffusion coefficients
      measured were significantly lower than those in pure solvent and they decreased
      with increasing agarose concentration. The gel diffusion coefficients obtained
      for pullulans decreased with increasing pullulan molecular weight. The same
      effect from increased molecular weight was seen in the liquid diffusion
      coefficients measured by DLS. The pullulan partition coefficients obtained
      decreased with increasing molecular weight. However, pullulans with a larger
      Stokes' radius than BSA had partition coefficients that were higher or
      approximately the same as BSA. This implied that the pullulan molecules were more
      flexible than the BSA molecules. The results obtained for BSA in this study
      agreed well with other experimental studies. In addition, the magnitude of the
      relative standard deviation was acceptable and in the same range as for many
      other methods. The results thereby obtained showed that holographic
      interferometry is a suitable method for studying diffusion of macromolecules in
      gels.

PMID- 10918142
TI  - Large-scale prediction of phenotype: concept.
AB  - The capability to gather organism wide data has far outstripped the ability to
      understand it. Transforming large-scale data into a "better" cell requires tools
      that integrate physiology with its environment. One such tool is large-scale
      mathematical models that marry stoichiometry and kinetics with metabolic
      regulation and control. It is straightforward to determine stoichiometry (at
      least for central pathways), and kinetics can be roughly approximated where need
      be. However, the molecular details of the "metabolic wiring" managing the cell
      are often missing. Presented here is a surrogate for these missing details based
      on a simple premise; over evolutionary time, biological systems have developed
      objective-based programs that frugally manage gene expression and enzyme
      activity. Mathematically, this notion can be represented as sets of nonlinear
      control or "management" problems which, when solved in parallel with the model
      balances, offer a prediction of how gene expression and enzyme activity are
      modulated, in the absence of specific mechanistic details. We present a model of
      Escherichia coli central carbon metabolism, describing batch aerobic growth on
      glucose, in which transcription, translation, and activity of the gene products
      of 45 genes is "managed" using this approach. The model consists of 122 species
      (metabolites, enzymes, mRNA pools, and biomass) and describes 46 reactions (17
      reversible). The model is identified (kinetic parameters as well as management
      structure) from metabolic flux ratio (METAFoR) analysis and physiological
      measurements. Simulations of a pyruvate kinase knockout strain are compared with
      experiments and it is shown the model is capable of accurately capturing the
      metabolic reprogramming resulting from the deletion. Analysis of the mRNA
      expression pattern, translational pattern and enzyme activity pattern of the wild
      type versus mutant indicates a combination of expression and specific activity
      shifts are responsible for observed differences. While being only a first step
      toward large-scale physiological modeling, this work is important in two ways.
      First, it strengthens the hypothesis that unknown mechanism can be reasonably
      approximated using objective-based management criteria. Second, it provides a
      dynamic means to couple large-scale analysis technologies with physiology at the
      single-gene, single-protein level.

PMID- 10918143
TI  - Optimization of repeated-batch transcription for RNA production.
AB  - A major obstacle to large-scale RNA production is the high raw material cost.
      This work focuses on reducing the cost of RNA produced by in vitro transcription.
      RNA can be produced by transcription from DNA templates immobilized on solid
      supports such as agarose beads, with yields comparable to traditional solution
      phase transcription. The advantage of immobilized DNA is that the templates can
      be recovered from the reaction and reused in multiple rounds, eliminating
      unnecessary disposal. Additionally, approximately 50% of the original RNA
      polymerase added to the reaction is also recovered in active form with the DNA
      and can be used for further rounds of repeated-batch transcription. Thus, adding
      only a fraction of the first-round enzyme concentration to subsequent rounds is
      sufficient for maintaining yields comparable to batch reactions for many rounds,
      with lowered cost. Results for two different DNA templates support a simplified
      model for repeated-batch transcription, based on the previous work of Davis and
      Breckenridge (J Biotechnol 1999;71:25-37). The model successfully predicts the
      yields for several of rounds of repeated-batch transcription using various enzyme
      addition schemes, and it was used to optimize the process by reducing the cost of
      raw materials per amount of RNA produced by 40-70%.

PMID- 10918144
TI  - Adsorption of Trichoderma reesei CBHI cellulase on silanized silica.
AB  - Adsorption kinetics and surfactant-mediated elution of Trichoderma reesei CBHI
      cellulase were recorded in situ, at hydrophobic, silanized silica. Experiments
      were performed at different solution concentrations, ranging from 0.001 to 0.98
      mg/mL. Adsorbed enzyme was partially elutable upon rinsing, with the amount of
      adsorbed mass remaining being highest at intermediate concentrations. In
      addition, the resistance to elution with buffer was generally lower at higher
      concentrations, and the resistance to elution with surfactant was generally lower
      at intermediate concentrations. These observations are tentatively explained with
      reference to a mechanism allowing for adsorption of associated monomers of CBHI
      as well as free monomers.

PMID- 10918145
TI  - Investigation of photobioreactor design for enhancing the photosynthetic
      productivity of microalgae.
AB  - As photosynthetic efficiencies are relatively high at irradiation levels of <500
      micromol m(-2) s(-1), photosynthetic productivity could be increased by
      redistributing strong light over a larger photo-receiving area using conical,
      helical, tubular photobioreactors (HTP). When Chlorella were exposed to light
      irradiation of 980 micromol m(-2) s(-1), the ratio of productivities was
      1.00:1.13:1.23:1.66 for conical HTPs with cone angles of 180 degrees (flat type),
      120 degrees, 90 degrees, and 60 degrees, respectively. This suggests that photo
      redistribution technology is a highly effective and convenient approach for
      increasing the photosynthetic productivity of microalgae.

PMID- 10918146
TI  - Listen to the patient. It frightens me. It's personal. Hurry.
AB  - What follows are the perceptions of two individuals--a patient and a highly
      respected medical oncologist who did not participate in the care of this patient
      but read the patient's essay. We encourage readers to share their thoughts about
      these essays in correspondence.

PMID- 10918147
TI  - A physician's point of view
AB  - What follows are the perceptions of two individuals-a patient and a highly
      respected medical oncologist who did not participate in the care of this patient
      but read the patient's essay. We encourage readers to share their thoughts about
      these essays in correspondence. Barrie E. Cassileth, Ph.D. Department of
      Integrative Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York
      A. Bernard Ackerman, M.D. Ackerman Academy of Dermatopathology, New York, New
      York Copyright 2000 American Cancer Society.

PMID- 10918148
TI  - Caveats for modeling disease free survival after radical prostatectomy.

PMID- 10918149
TI  - Caveats for modeling disease free survival after radical prostatectomy

PMID- 10918150
TI  - The Augsburg Consensus. Techniques of lymphatic mapping, sentinel
      lymphadenectomy, and completion lymphadenectomy in cutaneous malignancies.

PMID- 10918151
TI  - A comparison of the Chinese 1992 and fifth-edition International Union Against
      Cancer staging systems for staging nasopharyngeal carcinoma.
AB  - BACKGROUND: The Chinese 1992 staging system for nasopharyngeal carcinoma (NPC)
      has been widely adopted in mainland China since 1992. The fifth edition of the
      International Union Against Cancer (UICC) TNM classification defines new rules
      for classifying NPC. The current study compares the two in predicting NPC
      prognosis. METHODS: Four hundred eleven NPC patients, most of whom had disease of
      undifferentiated histologic type and were treated in a constant fashion and with
      definitive intent with radiation therapy alone, entered this comparative study.
      The patients were restaged according to the rules of the fifth edition of the
      UICC staging manual and the Chinese 1992 staging system. RESULTS: In the opinion
      of the authors, the predictive power of the Chinese 1992 T classification was
      superior. Conversely, the authors felt that the UICC N classification was more
      reasonable. The patients were categorized more evenly by the UICC stages than by
      the Chinese 1992 stages. The 5-year disease specific survival rates for patients
      in corresponding stages of both systems were almost identical despite differences
      in the criteria defining T and N classifications. Statistical analysis showed
      that the agreement rate was 72%. There were some agreement and correlation
      between the two staging systems. CONCLUSIONS: Both systems are essentially
      similar. Each system appears to have some subtleties that could improve the
      outcome prediction of the other system if the two were somehow combined. However,
      it appeared to the authors that the UICC system was slightly better.

PMID- 10918152
TI  - Significance of involvement by squamous cell carcinoma of the ducts of esophageal
      submucosal glands. Analysis of 201 surgically resected superficial squamous cell
      carcinomas.
AB  - BACKGROUND: Ductal involvement (DI) is often observed in superficial squamous
      cell carcinoma of the esophagus (SSCCE), defined as carcinoma with invasion
      limited to the submucosa. The purpose of this study was to clarify the
      clinicopathologic significance of DI in SSCCE. METHODS: Two hundred one
      surgically resected lesions from 140 patients with SSCCE were examined
      histopathologically. Clinicopathologic factors, such as macroscopic type, tumor
      location, maximum tumor size, depth of invasion, lymphatic and blood vessel
      permeation, lymph node metastasis, and prognosis, were examined to investigate
      the association between these factors and the presence of DI. RESULTS: Of the 201
      SSCCE lesions, 43 (21.3%) had 152 DIs (1-32 DIs per lesion). The DI always
      remained in situ, and there were no tumors showing submucosal invasion through
      the DI. As for the relation between clinicopathologic factors and the presence of
      DI, multivariate analysis showed only maximum tumor size to correlate with the
      presence of DI (P < 0.0001). There were no significant differences between DI
      negative and DI positive lesions in tumor location, macroscopic type, lymphatic
      and blood vessel permeation, lymph node metastasis, or prognosis. In 83 mucosal
      carcinomas, including in situ carcinomas or carcinomas that invaded no deeper
      than the lamina muscularis mucosa, no lymph node metastasis was found, and the 5
      year survival rate was 100% (unaffected by the presence of DI). Among these 83
      lesions, DI was found in 11 (13.8%), of which 6 (7.2%) had DI extending to the
      submucosal layer. CONCLUSIONS: These results indicate that DI as a pathway of
      tumor spread to the deeper layer is of little significance in squamous cell
      carcinoma of the esophagus, and that mucosal carcinomas with DI that extends to
      the submucosa should not be classified as submucosal carcinoma.

PMID- 10918153
TI  - Early and late recurrence after gastrectomy for gastric carcinoma. Univariate and
      multivariate analyses.
AB  - BACKGROUND: To the authors' knowledge, there are few studies regarding the
      predictors of early and late recurrence after gastrectomy for gastric carcinoma,
      and it is unknown whether prognostic factors can be applied to the timing of
      recurrence. The current study analyzed patients who died of recurrent gastric
      carcinoma and clarified histopathologic indicators associated with early and late
      recurrence. METHODS: The study included 138 patients who died of recurrent
      gastric carcinoma after gastrectomy that was performed in the Department of
      Surgery I, Oita Medical University, between 1982-1995. Clinicopathologic findings
      were compared between 104 patients who died within 2 years after gastrectomy
      (early recurrence group) and 34 patients who died > 2 years after gastrectomy
      (late recurrence group). Multivariate analysis was performed to determine the
      independent factors correlated with the timing of recurrence. RESULTS: When
      compared with the late recurrence group, the early recurrence group was
      characterized by a tumor size >/= 5 cm (92% in the early recurrence group vs. 74%
      in the late recurrence group), positive lymphatic invasion (64% vs. 38%),
      extended lymph node metastasis (73% vs. 35%), Stage III or IV disease (87% vs.
      62%), and limited lymph node dissection (32% vs. 3%). The mean survival time was
      influenced by the lymphatic invasion (P < 0.01), vascular invasion (P < 0.05),
      level of lymph node metastasis (P < 0.01), stage of disease (P < 0.01), and
      extent of lymph node dissection (P < 0.01). On multivariate analysis, survival
      time was found to be associated independently with the stage of disease (Stage I,
      II vs. Stage III, IV) or the level of lymph node metastasis (N0, N1 vs. N2, N3).
      CONCLUSIONS: The stage of disease and level of lymph node metastasis were found
      to be the most significant factors independently associated with the survival
      time after gastrectomy for gastric carcinoma. Patients with more advanced stage
      of disease (Stage III, IV) or those with extended lymph node metastasis (N2, N3)
      frequently died of recurrence within 2 years after gastrectomy.

PMID- 10918154
TI  - Modulation of tumor-induced lethality after pneumoperitoneum in a mouse model.
AB  - BACKGROUND: To the authors' knowledge, a generally accepted approach to prevent
      increased intraabdominal tumor implantation after laparoscopic cancer surgery
      does not exist. METHODS: One week after establishing an ovarian carcinoma cell
      line in black mice intraabdominally (n = 156), a carbon dioxide pneumoperitoneum
      (Group 1: n = 78) was administered. The effect of this procedure on tumor-induced
      lethality and the therapeutic effect of mitoxantrone and taurolidin mixed with
      heparin and sodium chloride was investigated. The different drugs were added
      immediately after the release of the pneumoperitoneum and after 48 hours. The 78
      control animals received the drugs at the same time without preexisting
      pneumoperitoneum. Survival time was registered. RESULTS: The survival time was
      reduced significantly in all pneumoperitoneum groups compared with the
      corresponding control group without pneumoperitoneum. The effect of mitoxantrone
      on survival time (mean, 62.08 days) was diminished significantly by the
      application of a pneumoperitoneum (mean, 34.27 days). Taurolidine/heparin
      appeared to have a positive effect on survival time only in the case of a
      previous pneumoperitoneum (mean of 21.12 days vs. mean of 16.04 days in the
      pneumoperitoneum control group; P < 0.001). CONCLUSIONS: The induction of a
      pneumoperitoneum appears to decrease survival time by increasing tumor cell
      growth and decreases the efficacy of intraperitoneal chemotherapy. The effects of
      pneumoperitoneum appear to be reduced by the use of heparin/taurolidine, which
      theoretically blocks extracellular matrix binding domains and inhibits the
      production of interleukin-1.

PMID- 10918155
TI  - Fibrous pseudocapsule of metastatic liver tumors from colorectal carcinoma.
      Clinicopathologic study of 152 first resection cases.
AB  - BACKGROUND: The presence of pseudocapsules of liver tumors has been recognized in
      hepatocellular carcinoma and is known to be a favorable prognostic factor.
      Although several studies have reported pseudocapsules around metastatic liver
      tumors, to the authors' knowledge there have been few evaluations of the clinical
      significance of such features in patients with metastatic colorectal carcinoma.
      METHODS: A clinicopathologic study was conducted in 152 patients who underwent
      initial hepatic resection for metastatic colorectal carcinoma. RESULTS: The
      presence of fibrous tissue between the tumor and the surrounding hepatic
      parenchyma was noted in 93 of the 152 patients (61%) with colorectal liver
      metastases. These patients were classified as having a thin pseudocapsule (n =
      46) or a thick pseudocapsule (n = 47), according to the number of collagen
      bundles (< 10 or >/= 10) between the tumor and the hepatic parenchyma in
      histologic sections. Pathologically, the presence and thickness of the fibrous
      pseudocapsule were related closely to less invasiveness into adjacent vessels (P
      = 0.004) and the presence of macroscopic intrabile ductal invasion (P = 0.008).
      The postresection survival was significantly better in patients with thick or
      thin pseudocapsules than in those without a pseudocapsule (3-year and 5- year
      cumulative survival rates of patients with no, thin, and thick pseudocapsules
      were 41% and 31%, respectively, 71% and 64%, respectively, and 88% and 88%,
      respectively; P < 0.001). In a multivariate analysis using the Cox proportional
      hazards model, after adjusting for other potential prognostic factors (vascular
      invasion, bile ductal invasion, number of tumors, tumor size, and curativeness of
      surgery), the presence of a fibrous pseudocapsule was an independent predictor of
      a favorable outcome after hepatic resection. CONCLUSIONS: The presence of fibrous
      tissue between the tumor and the liver parenchyma was a promising indicator of a
      better prognosis after resection in patients with colorectal liver metastases.

PMID- 10918156
TI  - Microwave coagulation therapy for multiple hepatic metastases from colorectal
      carcinoma.
AB  - BACKGROUND: Compared with other treatments, microwave coagulation is a relatively
      less invasive treatment for various kinds of solid tumors. Although its
      effectiveness in primary hepatocellular carcinoma has been shown, its
      effectiveness in the treatment of hepatic metastases from colorectal carcinoma
      has been unclear. The aim of this study was to evaluate its effectiveness in the
      treatment of multiple hepatic metastases from colorectal carcinoma by comparing
      this technique with that of hepatic resection. METHODS: Thirty patients with
      multiple metastatic colorectal tumors in the liver who were potentially amenable
      to hepatic resection were randomly assigned to treatment with microwave
      coagulation (14 patients) or hepatectomy (16 patients). Tumors in the microwave
      group were coagulated after laparotomy at an output of 60-100 W for 2-20 minutes
      under the guide of ultrasonography, whereas tumors in the hepatectomy group were
      treated with lobectomy, segmentectomy, subsegmentectomy, and/or wedge resection.
      RESULTS: One-, 2-, and 3-year survival rates and mean survival times were 71%,
      57%, 14%, and 27 months, respectively, in the microwave group, whereas they were
      69%, 56%, 23%, and 25 months, respectively, in the hepatectomy group. The
      difference between these two groups was statistically not significant (P = 0.83).
      On the other hand, the amount of intraoperative blood loss in the microwave group
      (360 +/- 230 mL) was smaller than that in the hepatectomy group (910 +/- 490 mL,
      P < 0.05). Blood transfusion was necessary for 6 patients in the hepatectomy
      group, but it was not necessary in the microwave group. CONCLUSIONS: Microwave
      coagulation therapy is suggested to be equally effective as hepatic resection in
      the treatment of multiple (two to nine) hepatic metastases from colorectal
      carcinoma, whereas its surgical invasiveness is less than that of hepatic
      resection.

PMID- 10918157
TI  - Distribution of colorectal liver metastases in patients referred for hepatic
      resection.
AB  - BACKGROUND: There is a perception that streamline flow of blood in the portal
      vein may influence the anatomic distribution of liver metastases, depending on
      the site of the primary tumor. It has previously been reported that cancers
      arising in the right colon are distributed to the right lobe of the liver 10
      times more commonly than to the left lobe, whereas liver metastases from tumors
      arising from the left colon and rectum are believed to be distributed
      homogenously. METHODS: Data were collected prospectively on the anatomic site of
      hepatic metastases in 207 patients with colorectal metastases referred for
      consideration for surgery. Anatomic site was established by a combination of
      computed tomography scanning and either laparoscopic or intraoperative
      ultrasonography. The site of the primary tumor was known in all cases. RESULTS: A
      total of 708 metastases were identified, of which 67% were in the right hemiliver
      and 33% were in the left. The ratio of involvement of the right and left
      hemilivers by metastases arising from right colon tumors was 2. 02:1 and for left
      colon tumors 2.1:1. When patients with unilobar disease only were considered, the
      ratio of involvement of the right and left hemilivers increased to 2.9:1, but
      again no difference was evident that depended on the site of the primary tumor.
      CONCLUSIONS: This study could not find any evidence to support a differential
      pattern of metastasis within the liver dependent on the location of the primary
      colorectal carcinoma.

PMID- 10918158
TI  - Thymidylate synthase quantitation and in vitro chemosensitivity testing predicts
      responses and survival of patients with isolated nonresectable liver tumors
      receiving hepatic arterial infusion chemotherapy.
AB  - BACKGROUND: Patients with isolated, nonresectable liver tumors may receive
      regional hepatic arterial infusion (HAI) chemotherapy with response rates of
      about 50%. The objective of this study was to investigate the value of
      thymidylate synthase (TS) determination in combination with in vitro
      chemosensitivity testing to predict the responses and survival of patients
      receiving HAI. METHODS: TS mRNA expression was quantitated using a reverse
      transcription-polymerase chain reaction technique with beta-actin as the internal
      standard. In vitro chemosensitivity testing was performed with tumor cell
      suspensions using the human tumor colony-forming assay (HTCA). RESULTS: An
      analysis of the test combination in 24 consecutive patients revealed that 77% (10
      of 13) of the sensitive and 9% (1 of 11) of the resistant patients had complete
      or partial clinical responses. Sensitive patients were 8.5-fold more likely to
      respond (P = 0.0036) and displayed with 32 months (range, 5-75 months) a longer
      median survival than resistant patients with 17 months (range, 3-28 months, P =
      0.003). Analysis of the Kaplan-Meier curves revealed that sensitive patients had
      a higher overall survival probability, as determined by the log rank test (P =
      0.044). CONCLUSIONS: These results suggest that the clinical outcomes of patients
      receiving HAI therapy may be predictable with TS quantitation and HTCA. It is
      possible, therefore, that this combination may be used in the future to select
      patients with liver tumors who will benefit from HAI before the start of regional
      chemotherapy.

PMID- 10918159
TI  - Carriage of HFE mutations and outcome of surgical resection for hepatocellular
      carcinoma in cirrhotic patients.
AB  - BACKGROUND: Aggressive hepatocellular carcinoma (HCC) complicates frequently
      hereditary hemochromatosis, a disease for which a strong candidate gene, named
      HFE, has recently been identified. Patients with HCC who are heterozygotes for
      mutations in the HFE gene might have distinct features and a distinct disease
      course. METHODS: The presence of the 2 mutations associated with hereditary
      hemochromatosis (C282Y and H63D) was sought by restriction fragment length
      polymorphism in 61 cirrhotic patients (46 males and 15 females) who underwent
      resection for HCC at a single institution. RESULTS: There were 4 heterozygotes
      for the C282Y mutation and 6 homozygotes + 20 heterozygotes for the H63D
      mutation, with no compound heterozygotes. Carriage of >/= 1 HFE mutated allele
      was significantly more frequent in HCC patients than in 149 control subjects (44%
      vs. 29%, P = 0.005). Among C282Y heterozygotes, 3 of 4 were female, compared with
      12 of 57 wild-type carriers (P = 0.015); no gender distribution existed among
      patients carrying H63D alleles (6 of 26 vs. 9 of 35, P = 0.813). Survival was
      longer for patients with wild-type HFE than for those with mutated HFE (67% vs.
      22% at 3 years; hazard ratio = 0.42, 95% confidence interval = 0.21-0.80) (P <
      0.01). The negative effect on survival that resulted from possessing >/= 1 HFE
      mutated allele was maintained even after adjustment for gender, age, presence of
      tumor capsule, presence of comorbid factors, Okuda stage, Edmonson grading, and
      number of lesions (P = 0.01). CONCLUSIONS: Testing for HFE mutations may help
      identify HCC patients with dismal prognoses for whom surgical resection may not
      represent the best treatment option.

PMID- 10918160
TI  - A novel arterial infusion chemotherapy for the treatment of patients with
      advanced pancreatic carcinoma after vascular supply distribution via
      superselective embolization.
AB  - BACKGROUND: Patients with American Joint Committee on Cancer Stage IV advanced
      pancreatic carcinoma have been treated by systemic chemotherapy, intraarterial
      chemotherapy, radiation therapy, and multidisciplinary treatment using a
      combination of these. However, the outcome has not always been satisfactory. In
      the current study the authors describe the method and results of a new
      chemotherapy for advanced pancreatic carcinoma. METHODS: To restrict the blood
      flow into the pancreas (mainly to the great pancreatic artery and the caudal
      pancreatic artery), the peripancreatic blood vessels were embolized
      superselectively with microcoils. In 31 patients with advanced pancreatic
      carcinoma, the catheter tip for the arterial infusion chemotherapy was placed in
      the splenic artery just proximal to the branching of the great pancreatic artery
      when the treatment was given for primary tumors, and in the common hepatic artery
      when the treatment was given for a metastatic liver lesion. The other end of the
      catheter was connected to an implanted injection port embedded in the femoral
      region, and 5-fluorouracil and cisplatin were administered by continuous arterial
      infusion. RESULTS: Of the 31 patients with advanced pancreatic carcinoma, 23
      (74%) underwent hemodynamic change and arterial infusion chemotherapy, with a
      response rate of 73.9% (complete response rate of 8.7% and a partial response
      rate of 65.2%) and a mean survival period of 18.26 +/- 10.06 months. The 1-year,
      2-year, and 3-year survival rates were 90.9%, 42. 8%, and 18.3%, respectively,
      with a mean survival period of 19.0 months. Of these 23 patients, the 16 patients
      with liver metastases had a response rate of 68.8% and a mean survival period of
      16.25 +/- 8.35 months, whereas the 7 patients without liver metastases had a
      response rate of 87.5% and a mean survival period of 22.86 +/- 12.69 months.
      CONCLUSIONS: In patients with Stage IV advanced pancreatic carcinoma, arterial
      infusion chemotherapy after hemodynamic change was found to be effective against
      both primary tumors and metastatic liver lesions. The authors believe that the
      treatment presented in the current study should be attempted, even in patients
      with advanced pancreatic carcinoma, as long as the blood vessels for vascular
      supply distribution exist.

PMID- 10918161
TI  - Survival advantage of combined chemoradiotherapy compared with resection as the
      initial treatment of patients with regional pancreatic carcinoma. An outcomes
      trial.
AB  - BACKGROUND: Resection of pancreatic carcinoma is resource-intensive with a
      limited impact on survival. Chemotherapy and/or radiotherapy (RT) have been shown
      to be effective palliation. To examine whether preoperative chemoradiotherapy as
      the initial treatment improves survival for patients with a regional pancreatic
      adenocarcinoma with a minimal chance of being resected successfully, an outcomes
      trial was conducted. METHODS: Patients with radiologically regional tumors were
      staged by laparotomy and/or computed tomography followed by endoscopic
      ultrasonography, angiography, and/or laparoscopy. Those with locally invasive,
      unresectable, regional pancreatic adenocarcinoma initially were treated with
      simultaneous split-course RT plus 5-fluorouracil, streptozotocin, and cisplatin
      (RT-FSP) followed by selective surgery (Group 1). Patients determined to have a
      resectable tumor initially underwent resection without preoperative
      chemoradiotherapy, with or without postoperative chemoradiotherapy (Group 2).
      RESULTS: Over 8 years 159 patients presenting with nonmetastatic pancreatic
      adenocarcinoma were administered RT-FSP or underwent surgery for resection. Group
      1, comprised of 68 patients initially treated with RT-FSP, had a 0% mortality
      rate within 30 days of entry. In 20 of 30 patients undergoing surgery after RT
      FSP, tumors were downstaged and resected. Group 2, comprised of 91 patients who
      initially underwent successful resection, had a 5% mortality rate within 30 days
      of entry. Postoperatively, 63 of these patients received chemotherapy with or
      without RT. The median survival for Group 1 was 23.6 months compared with 14.0
      months for Group 2 (P = 0.006) despite more advanced disease cases in Group 1.
      Survival favored RT-FSP regardless of whether lymph nodes were malignant. The
      dominant prognostic factor of earlier stage pancreatic carcinoma having an
      expected survival advantage was reversed by the initial nonoperative treatment.
      CONCLUSIONS: Based on a reversal of the expected trend that patients with earlier
      stage resectable carcinoma (T1,2, N0,1, M0) who undergo removal of their tumors
      survive longer than patients with more advanced regional disease (T3, N0,1, M0),
      survival was found to improve significantly for patients reliably staged as
      having locally invasive, unresectable, nonmetastatic pancreatic adenocarcinoma
      when initially treated with RT-FSP.

PMID- 10918162
TI  - Weekly docetaxel in the treatment of elderly patients with advanced nonsmall cell
      lung carcinoma. A Minnie Pearl Cancer Research Network Phase II Trial.
AB  - BACKGROUND: Weekly administration of docetaxel was found to reduce
      myelosuppression and other nonhematologic toxicities when compared with
      administration every 3 weeks. In the current Phase II trial, the authors
      evaluated the feasibility, toxicity, and efficacy of weekly docetaxel in the
      treatment of elderly patients with newly diagnosed advanced nonsmall cell lung
      carcinoma. METHODS: Thirty-nine patients with advanced, previously untreated
      nonsmall cell lung carcinoma entered this Phase II trial between February 1998
      and January 1999. Patients were required either to be age >/= 65 years or to be
      poor candidates for combination chemotherapy due to coexistent medical illnesses.
      All patients received docetaxel, 36 mg/m(2), administered weekly for 6
      consecutive weeks, followed by 2 weeks without treatment. Patients were
      reevaluated after 8 weeks of treatment; responding patients continued weekly
      docetaxel for a maximum of 32 weeks or until disease progression. RESULTS: Weekly
      docetaxel was well tolerated by this elderly group of patients with nonsmall cell
      lung carcinoma. Grade 3 leukopenia was noted in only 3 patients (8%), and no
      patient developed Grade 4 myelosuppression. Grade 3/4 nonhematologic toxicity
      also was uncommon; fatigue/asthenia was reported in 4 patients (10%). Seven of 38
      evaluable patients (18%) had objective responses to weekly docetaxel whereas an
      additional 13 patients (34%) had a minor response or stable disease at first
      reevaluation. The median survival in this group of elderly patients was 5 months,
      with a 1-year actuarial survival rate of 27%. CONCLUSIONS: The results of the
      current study show that weekly docetaxel is active and well tolerated in elderly
      patients with advanced nonsmall cell lung carcinoma and provides an additional
      treatment option for these patients, who often tolerate combination chemotherapy
      regimens poorly.

PMID- 10918163
TI  - Intracellular distribution of macrophage migration inhibitory factor predicts the
      prognosis of patients with adenocarcinoma of the lung.
AB  - BACKGROUND: Macrophage migration inhibitory factor (MIF) is known to be a
      proinflammatory cytokine and glucocorticoid-induced immunomodulator as well as a
      regulator of tumor growth. Although positive and negative effects of MIF on tumor
      cell growth have been reported, to the authors' knowledge the precise role of MIF
      in tumorigenesis remains unclear. In the current study the authors assessed
      expression of MIF protein and mRNA in lung adenocarcinomas with regard to patient
      prognosis. METHODS: Immunohistochemical analysis was performed on tissue
      specimens surgically obtained from 74 patients with primary lung adenocarcinoma
      (American Joint Committee on Cancer pathologic Stages I, II, and IIIa). In
      addition, expression of MIF mRNA in the cancerous tissue was investigated using
      in situ hybridization. Patient prognosis was evaluated with regard to MIF
      expression levels and its distribution was analyzed with the Kaplan-Meier method.
      RESULTS: MIF mRNA and MIF protein were observed in the bronchial epithelium,
      alveolar epithelium, vascular smooth muscle, and alveolar macrophages in the
      normal lung tissue. In tumor tissue from lung adenocarcinoma specimens, both MIF
      mRNA and protein were observed at much higher levels than in the normal alveolar
      epithelium. MIF protein was observed diffusely in the cytoplasm of tumor cells in
      all tumor specimens examined. MIF protein also was observed in the nuclei of
      tumor cells from 59 patients (79.7%), whereas it was not observed in the nuclei
      of tumor cells from 15 patients (20.3%). The patients without nuclear MIF
      expression had a worse prognosis compared with those patients with MIF expression
      in the nuclei (P = 0.04). CONCLUSIONS: The results of the current study suggest
      that intracellular MIF distribution predicts patient prognosis in individuals
      with adenocarcinoma of the lung.

PMID- 10918164
TI  - Patterns of detection in patients with cutaneous melanoma.
AB  - BACKGROUND: Despite the importance of early detection in preventing mortality
      from melanoma, little is known regarding how patients with the disease come to
      diagnosis. METHODS: The authors prospectively evaluated 471 newly diagnosed
      melanoma patients between 1995 and 1998. Patients completed a questionnaire that
      included 1) identification of the person who detected the lesion, 2) the anatomic
      location of the lesion, and 3) family history of melanoma. Logistic regression
      analysis was performed to examine the relation between detection patterns and
      lesion thickness, adjusting for age, gender, anatomic site of the primary lesion,
      and family history of melanoma. RESULTS: The majority of patients detected their
      own melanoma (n = 270; 57%). Females were more likely to self-detect than males
      (69% vs. 47%; P < 0.0001). Physicians detected the melanoma in 16% of patients (n
      = 74), followed by "spouse" in 11% of patients (n = 51). Within this group,
      detection by wives was 7.5 times more common than detection by husbands (P <
      0.0001). Logistic regression analysis revealed that physicians were 3.6 times
      more likely to detect thin lesions (</=0.75 mm) compared with nonphysician
      detectors (95% confidence interval [95% CI], 2.1, 6.5; P = 0.0001). In addition,
      patients who reported a family history of melanoma had a 2.7-fold increased
      likelihood of presenting with a thin lesion (95% CI, 1.6, 4.7; P = 0.0003).
      CONCLUSIONS: Physician detection and a report of a family history of melanoma are
      associated with the presentation of patients with early melanoma, suggesting that
      awareness of the disease among physicians and the public is critical for
      preventing mortality from melanoma. Increasing melanoma awareness in males may be
      a particularly effective means of secondary prevention.

PMID- 10918165
TI  - Trends in mortality from malignant melanoma in Sweden, 1970-1996.
AB  - BACKGROUND: The rise in melanoma-related mortality in Sweden has been less
      pronounced than the increase in incidence. Interventional activities aimed at
      early detection may have contributed to this discrepancy. METHODS: Individuals
      with malignant melanoma as the underlying cause of death between 1970 and 1996 (n
      = 7177) formed the basis of this study. Annual age-standardized mortality rates
      were calculated using the direct method of standardization with the Swedish
      population of 1970 as reference. Temporal trends in the standardized rates were
      evaluated using a log-linear model. The effects of age, period, and cohort on the
      mortality trends were estimated using a Poisson regression model. RESULTS: Since
      the mid-1980s, melanoma-related mortality in Sweden has leveled off, with no
      further increase during the last 10-15 years. The contribution to the mortality
      from noncutaneous melanoma was proportionally stable (20-25%) during the studied
      period. In females, a significant decrease in mortality from cutaneous melanoma
      was shown for the period of 1987-1996 with an estimated annual decrease of -2.3%
      (95% confidence interval: -4.3 to -0.3). This trend appeared to be more
      pronounced in the Stockholm-Gotland region. The observed trends were best
      explained with the age-period model in both genders. CONCLUSIONS: Melanoma
      related mortality in Sweden has leveled off since the mid-1980s. During the
      period 1987-1996, a statistically significant downward trend was observed for
      females. This trend coincides with increased preventional activities.

PMID- 10918166
TI  - Adjuvant therapy of melanoma with interferon-alpha-2b is associated with mania
      and bipolar syndromes.
AB  - BACKGROUND: The use of a high dose regimen of interferon-alpha-2b (IFN) has
      recently been demonstrated to benefit patients with resected high risk melanoma.
      The incidence of melanoma is rising rapidly, and the use of this regimen is
      becoming increasingly common. IFN has been associated with numerous psychiatric
      side effects. METHODS: The authors describe four melanoma patients treated with
      adjuvant IFN who developed a manic-depressive syndrome or mood instability with
      therapy, and they review the literature on mania and the mixed affective
      syndromes associated with IFN. RESULTS: The authors suggest that IFN may induce a
      mixed affective instability, and that patients risk developing hypomania or mania
      as IFN doses fluctuate or as IFN-induced depression is treated with
      antidepressants alone. Mania is particularly associated with dose reductions or
      pauses in IFN treatment. The risk of mood fluctuation continues after treatment
      with IFN stops, and patients should be monitored for 6 months following
      completion of therapy. Gabapentin appeared effective as monotherapy for acute
      mania, as an antianxiety agent, as a hypnotic, and as a mood stabilizer in these
      individual cases. CONCLUSIONS: Mania and mood instability can occur in patients
      being treated with IFN therapy for melanoma. In this study, gabapentin was an
      effective mood-stabilizing agent for these patients.

PMID- 10918168
TI  - The association of increased weight, body mass index, and tissue density with the
      risk of breast carcinoma in Vermont.
AB  - BACKGROUND: Etiologic studies of breast carcinoma have indicated that weight,
      body mass index (BMI), and breast tissue density are important determinants of a
      woman's risk for the disease. This study looked at the independent effects of
      these risk factors. METHODS: Data from the Vermont Breast Cancer Surveillance
      System (VBCSS), collected between May 1996 and November 1997, were used to
      identify 529 breast carcinoma cases with no prior history of the disease. Each
      case was matched to four randomly chosen women of the same age who had mammograms
      during the same time period and had no biopsy-confirmed breast carcinoma.
      Logistic regression was used to assess the effects of weight, BMI, and breast
      tissue density on breast carcinoma risk for pre- and postmenopausal women.
      RESULTS: Weight and BMI were found to be significantly associated with
      postmenopausal breast carcinoma after adjustment for breast density, and vice
      versa. The density-adjusted odds ratio for women weighing over 81 kg, relative to
      women weighing under 63 kg, was 2.1, with a 95% confidence interval (CI) of 1.3
      3.2. Relative to women with breasts consisting entirely of fat, the weight
      adjusted odds ratios for women with heterogeneously dense and extremely dense
      breasts were 2.3 (CI: 1.3-4.3) and 4.5 (CI: 1.9-10.6), respectively. CONCLUSIONS:
      Among postmenopausal Vermont women, weight, BMI, and breast density were
      independently associated with breast carcinoma risk. Because breast density and
      weight or BMI are inversely related, estimates of their independent effects
      should be used when evaluating a woman's risk for breast carcinoma.

PMID- 10918167
TI  - Predictors of skeletal complications in patients with metastatic breast
      carcinoma.
AB  - BACKGROUND: The high rate of incidence of skeletal complications in women with
      metastatic breast carcinoma appears to contribute significantly to their
      morbidity. Although recent trials have demonstrated the efficacy of
      bisphosphonates in preventing skeletal complications in selected patients, to the
      authors' knowledge the incidence rate of skeletal complications in an unselected
      population of women with metastatic breast carcinoma is unknown. The current
      study was designed to examine the incidence rate of skeletal complications in a
      large unselected group of women with metastatic breast carcinoma to determine
      predictors of these complications. METHODS: All women (n = 718) diagnosed with
      metastatic breast carcinoma between 1981-1991 at the study institution were
      studied retrospectively. RESULTS: Greater than 50% of the women developed
      skeletal complications; among these women, 51% had > 1 complication.
      Approximately 80% of those with bone-limited disease at the time of diagnosis
      developed complications, as did 60% of those with bone and visceral disease and
      21% of those with no bone disease. By univariate analysis, the site of initial
      metastatic disease, abnormal alkaline phosphatase, and a disease free interval of
      < 3 years were predictive of skeletal complications. Multivariate analysis
      revealed that bone involvement at the time of diagnosis was predictive of
      subsequent skeletal complications. CONCLUSIONS: In this large retrospective study
      with extensive follow-up, skeletal complications were extremely common and
      repetitive, although complications predated patient death by >/= 1 year in the
      group of women presenting with any bone disease. The presence of bone disease at
      the time of initial presentation was predictive of skeletal complications. In
      this group of patients, the authors were unable to identify a subgroup with a low
      rate of skeletal complications.

PMID- 10918169
TI  - Case-control study of plasma folate, homocysteine, vitamin B(12), and cysteine as
      markers of cervical dysplasia.
AB  - BACKGROUND: An association between B-complex vitamins and related compounds with
      the development of cervical neoplasia is biologically plausible, yet to the
      authors' knowledge epidemiologic investigations of these potential biomarkers are
      limited. METHODS: A case-control study was designed to examine the relation
      between plasma folate, homocysteine, vitamin B(12), and cysteine and early,
      premalignant changes in cervical epithelial cells among women identified from
      several clinics on Oahu, Hawaii, between 1992 and 1996. Fasting blood samples for
      plasma nutrient analysis, cervical smears for cytologic diagnosis, exfoliated
      cervical cells for human papillomavirus DNA testing by polymerase chain reaction,
      and a personal interview were obtained from 185 women with atypical squamous
      cells of undetermined significance (ASCUS) of the cervix, 147 women with squamous
      intraepithelial lesions (SIL), and 191 women with cytologically normal
      (Papanicolaou) smears. RESULTS: Age-adjusted and ethnicity-adjusted mean plasma
      concentrations of cysteine, but not other nutrients, were significantly lower
      among ASCUS cases (P = 0.006) and SIL cases (P = 0.01) than controls. A positive
      trend in the odds ratio for SIL but not ASCUS was found for increased plasma
      homocysteine concentrations, but this finding was not statistically significant.
      High plasma levels of cysteine were associated with a reduced risk of ASCUS (P
      value for trend = 0.006), with an odds ratio of 0.3 (95% confidence interval, 0.2
      0.7) for the highest compared with the lowest quartile of cysteine concentration.
      A weak, negative relation between cysteine and the development of low grade SIL
      (LSIL) but not high grade SIL (HSIL) also was found. CONCLUSIONS: The results of
      the current study do not support the hypothesis that folate, homocysteine, or
      B(12) are markers of cervical dysplasia risk. A possible inverse association
      between plasma cysteine concentrations and the risk of cervical dysplasia needs
      further study.

PMID- 10918170
TI  - Absence of premalignant histologic, molecular, or cell biologic alterations in
      prophylactic oophorectomy specimens from BRCA1 heterozygotes.
AB  - BACKGROUND: The high mortality associated with ovarian carcinoma is largely a
      reflection of the inability to diagnose the disease at an early stage; the
      identification of a histologic lesion or molecular marker associated early stages
      of transformation would represent an important advance in understanding the
      natural history of this cancer. The existence of individuals with germline
      mutations in the ovarian and breast carcinoma susceptibility gene BRCA1
      represents a unique opportunity to search for such premalignant alterations in
      ovarian tissues that are at unusually high risk for tumorigenesis. In this study,
      the authors addressed the hypothesis that pathologically normal ovaries removed
      from BRCA1 heterozygotes are likely to display premalignant histologic,
      molecular, and/or cell biologic alterations that may provide insight into early
      stages of ovarian tumorigenesis. METHODS: Ovarian tissues from 18 BRCA1
      heterozygotes and from 20 age-matched controls were examined in a blinded fashion
      for histologic evidence of surface epithelial pseudostratification, epithelial
      inclusion cysts, deep cortical invaginations of surface epithelium, increased
      stromal cell activity, and surface papillomatosis. Immunohistochemical analyses
      for expression of BRCA1, p53, and ERBB-2 and quantitation of cell proliferation
      (Ki-67 expression) and apoptosis (TUNEL assay), were also performed on all
      specimens. RESULTS: Although histologic alterations were observed, there was no
      difference in frequency between cases and controls. Analysis of BRCA1 expression
      revealed ubiquitous nuclear immunoreactivity in the surface epithelial cells of
      all ovaries. Similarly, no evidence was found of p53 overexpression in any
      ovarian tissue or of a difference in ERBB-2 expression between cases and
      controls. Finally, no differences were observed in epithelial cell proliferation
      or apoptosis. CONCLUSIONS: Clinically, normal ovaries from BRCA1 heterozygotes do
      not show evidence of premalignant alterations in histology, molecular markers,
      cell proliferation, or apoptosis, indicating that such changes are likely rare.

PMID- 10918171
TI  - Conservative surgery to preserve ovarian function in patients with malignant
      ovarian germ cell tumors. A review of 74 cases.
AB  - BACKGROUND: Effective combination chemotherapy has improved the previously dismal
      prognosis for malignant ovarian germ cell tumors (MOGCT) dramatically. In young
      patients, conservative surgery with adjuvant chemotherapy has made the
      preservation of fertility possible, even in patients with advanced disease. The
      increase in cure rates has shifted the focus of recent studies to the long term
      menstrual, reproductive, and gynecologic outcomes in these patients. METHODS: The
      current study is a retrospective review of 74 patients with MOGCT treated by
      conservative surgery, retaining the uterus and contralateral ovary to preserve
      ovarian function, with or without chemotherapy. RESULTS: The mean age of the
      patients was 20.9 years (range, 10-35 years). The histologic subtypes included 31
      dysgerminomas (41.9%), 16 immature teratomas (21.6%), 13 endodermal sinus tumors
      (17.6%), 11 mixed germ cell tumors (14.9%), and 3 embryonal cell tumors (4.1%).
      There were 56 International Federation of Gynecology and Obstetrics (FIGO) Stage
      I tumors (75.7%), 3 Stage II tumors, (4.1%), 11 Stage III tumors (14.9%), and 4
      Stage IV tumors (5.4%). Adjuvant chemotherapy was administered in 47 patients
      (63.5%). The overall mean follow-up period was 52.1 months. There were 7
      recurrences (9.5%) and 2 deaths (2.7%). Survival for patients with Stage I
      disease was 98.2% and that for patients with advanced disease stages was 94.4%.
      During chemotherapy 61.7% of patients developed amenorrhea but 91.5% of these
      women resumed normal menstrual function on completion of chemotherapy. Fourteen
      healthy live births were recorded in the chemotherapy group and there were no
      documented birth defects. There was 1 case of infertility (1.4%). CONCLUSIONS:
      The surgical approach in young patients with MOGCT confined to a single ovary
      should aim to preserve fertility. Advanced disease is not usually accompanied by
      contralateral ovarian disease and should not necessarily contraindicate
      conservative surgery. The majority of these patients who have received
      combination chemotherapy resume normal ovarian function and can expect a normal
      fertility rate and healthy offspring.

PMID- 10918172
TI  - External beam radiotherapy and hyperthermia in the treatment of patients with
      locally advanced prostate carcinoma.
AB  - BACKGROUND: The current study was conducted to evaluate the combination of
      external beam radiation therapy and hyperthermia in the treatment of patients
      with locally advanced prostate carcinoma. METHODS: Twenty-six patients were
      treated on a Phase I/II protocol between June 1990 and April 1993. The median age
      of the patients was 69 years. Nine patients had well differentiated
      adenocarcinoma, ten patients had moderately differentiated adenocarcinoma, and
      six patients had poorly differentiated adenocarcinoma. All patients had American
      Urologic Society Stage C2-D1 adenocarcinoma. The median pretreatment prostate
      specific antigen (PSA) level was 29 ng/mL (range, 6-104 ng/mL). All patients
      received external beam radiation therapy using a four-field technique. The median
      radiation dose was 6,800 centigrays (cGy) given in 200-cGy fractions.
      Hyperthermia was administered concurrently with radiation therapy to temperatures
      of 42.5 degrees C for 30 minutes using a transrectal ultrasound applicator with 3
      thermometry probes, given as either a single treatment (9 patients) or as two
      treatments (17 patients). Overall survival (OS) and biochemical no evidence of
      disease (bNED) status were calculated using Kaplan-Meier analysis. A consensus
      conference definition of PSA failure was used. The Cox proportional hazards model
      was used for multivariate analysis. The median follow-up for all patients was 71
      months. RESULTS: The median time to PSA nadir was 15 months with a median PSA
      nadir value of 1.0 ng/mL. The median and 5-year OS was 88 months and 73%,
      respectively, and the median and 5-year bNED survival was 36 months and 35%,
      respectively. Multivariate analysis revealed only the pretreatment PSA level (P =
      0.03) and the PSA nadir reached (P < 0.01) to be significant predictors of bNED
      survival. The duration of hyperthermia therapy showed a trend toward significance
      for OS (P = 0.06). CONCLUSIONS: The current Phase I/II protocol evaluating the
      combination of prostate hyperthermia and external beam radiation therapy for the
      treatment of patients with locally advanced prostate carcinoma suggests prostate
      hyperthermia to be feasible with no apparent significant increased toxicity,
      although there was no significant improvement in treatment outcome when compared
      with other studies reported in the literature evaluating external beam radiation
      therapy with or without androgen suppression. However, further investigation into
      the duration as well as the temperature of the hyperthermia with a greater number
      of patients is warranted.

PMID- 10918173
TI  - Recursive partitioning for prognostic grouping of patients with clinically
      localized prostate carcinoma.
AB  - BACKGROUND: Patients treated with radical prostatectomy for clinically localized
      prostate carcinoma present considerable heterogeneity in terms of disease free
      survival outcome. Multiple studies have attempted to create prognostic groupings
      of these patients in the perioperative phase, using information available
      regarding several clinicopathologic variables. Such groupings allow physicians to
      make early yet prudent decisions regarding adjuvant combination therapies. The
      current study presents results from a statistical analysis that enables the
      natural identification of such prognostic groups. METHODS: Examination of
      consecutive radical prostatectomy specimens was performed between January 1991
      and December 1995 at Wayne State University, Harper Hospital, Detroit, Michigan.
      Disease free survival in a cohort of 485 of these men was analyzed using
      recursive partitioning and amalgamation technique. Clinicopathologic parameters
      evaluated included age, race, preoperative prostate specific antigen (PSA) level,
      clinical and pathologic stage, and Gleason grade of the fine-needle biopsy as
      well as the radical prostatectomy specimen. RESULTS: A binary decision tree
      representation was generated for classifying patients based on the
      clinicopathologic variables mentioned earlier. The worst prognosis was for
      patients with either advanced stage and a PSA level > 24.1 ng/mL or advanced
      stage, a PSA level </= 24.1 ng/mL, and age </= 65 years. This group had an
      estimated median disease free survival of only 10.3 months. Patients with lower
      pathologic stage, prostatectomy Gleason scores of </= 7, and a preoperative PSA
      level </= 22.7 ng/mL had the best prognosis. CONCLUSIONS: The recursive
      partitioning analyses allows easy characterization of a patient for prognosis
      shortly after radical prostatectomy. This will enable a physician to make more
      prudent decisions regarding whether to employ watchful waiting, proceed with
      accepted adjuvant therapy (radiotherapy or hormonal therapy), or refer patients
      to a research center that is able to administer experimental adjuvant therapy.
      [See editorial counterpoint on pages 232-3 and reply to counterpoint on pages 234
      5, this issue.]

PMID- 10918174
TI  - Loss of tissue transglutaminase as a biomarker for prostate adenocarcinoma.
AB  - BACKGROUND: Additional molecular tissue biomarkers for prostate carcinoma are
      needed to stratify patients with clinically suspicious findings, such as an
      elevated prostate specific antigen (PSA) with a negative biopsy, according to
      risk. METHODS: Prostate tissues from 43 cancer cases and 47 controls with no
      evidence of cancer were labeled for transglutaminase by immunohistochemistry.
      Immunoreactivity was quantified using the Autocyte Pathology Workstation. In
      addition, quantitative fluorescence image analysis was used to compare
      transglutaminase concentrations in cells obtained by fine-needle aspiration from
      excised prostates. Loss of gene expression was evaluated by reverse transcriptase
      polymerase chain reaction and growth with 5-azacytidine. RESULTS: Visually,
      benign glands from controls generally expressed tissue transglutaminase, whereas
      regions with adenocarcinoma generally were negative. With quantitative
      immunohistochemistry, 41 of 43 adenocarcinoma of the prostate (CaP) cases
      expressed lower mean percentage areas positive for transglutaminase than did 30
      of 30 benign prostatic hyperplasia (BPH) and 17 of 17 prostatitis cases (P <
      0.0001; odds ratio [OR], 1577; 95% confidence interval (CI), 74-33, 820; relative
      risk [RR], 25; 95% CI, 6-95). Quantitative immunofluorescence of 3277 cells
      collected by FNA from 19 CaP cases and 645 cells from 5 cases of BPH showed that
      the mean content of transglutaminase was 93 femtograms (fg) for the CaP-derived
      cells and 138 fg for the BPH cells (P < 0.0001). Receiver operating curve
      analysis of the immunohistochemistry data showed an optimized threshold produced
      95% sensitivity with 100% specificity. Growth of LNCaP cells with 5-azacytidine
      failed to stimulate transglutaminase expression, suggesting that loss of
      expression was likely not attributable to promoter methylation. CONCLUSIONS:
      Measurements of transglutaminase on tissue sections provides additional
      diagnostic information that is potentially useful for risk assessment of patients
      with suspicious clinical findings, such as nodules or positive PSA and negative
      biopsies, without overdetecting disease.

PMID- 10918175
TI  - Surgical and postoperative factors affecting length of hospital stay after
      radical prostatectomy.
AB  - BACKGROUND: Radical prostatectomy continues to comprise the mainstay of therapy
      for localized prostate carcinoma. However, caring for radical prostatectomy
      patients accounts for approximately half of the $1.7 billion annual cost of
      prostate carcinoma treatment. Length of stay (LOS) after surgery appears to be
      one of the main components of this cost. The first step in reducing cost is to
      identify those variables associated with LOS. Radical prostatectomy can be
      performed using two very different surgical techniques and with each technique
      different costs are incurred. The objective of the current study was to identify
      factors associated with LOS as a function of surgical approach. To reduce
      potential biases due to patient requests for longer hospitalization or physician
      preferences in that regard, secondary objectives were to identify factors
      associated with time to fluid intake (TTF) and time to consume solid foods (TTS).
      METHODS: An institutional-based, retrospective chart review of 313 men with
      clinically localized prostate carcinoma who underwent either a perineal (RPP) or
      retropubic (RRP) prostatectomy at a single university center from March 1988 to
      October 1996 was undertaken. Information regarding LOS was available for 311
      patients. Linear regression models were used to assess the association between
      covariables and LOS. Poisson regression models for count data were used to assess
      associations between covariables and the secondary endpoints of TTF and TTS.
      Covariables included: preoperative (age, race, prostate specific antigen, Gleason
      score, clinical stage, lymph node resection, comorbidity, and admission time),
      intraoperative (surgical approach, surgeon, operative time, estimated blood loss,
      transfusion requirement, anesthetic approach, and American Society of
      Anesthesiologists score), and postoperative (pain management complications and
      transfusions) parameters. RESULTS: The median LOS was 4 days (range, 1-19 days)
      for RPP and 5 days (range, 3-16 days) for RRP approaches. The final model
      included six main effects and three interaction terms. Overall, LOS decreased
      over time with LOS decreasing at a faster rate in patients who underwent RPP. In
      general, patients who underwent RRP had an increased LOS compared with patients
      who underwent RPP. Complications from surgery and age increased the LOS for all
      patients; however, the increase was greater in patients who underwent RPP. In
      addition, the use of intraoperative epidural anesthesia and the increased use of
      postoperative narcotics were associated with increased LOS for patients
      undergoing both surgical approaches. TTF and TTS were significantly longer for
      patients who underwent the retropubic approach compared with those patients who
      underwent the perineal approach. After adjustment for surgical approach no other
      covariables were found to be associated with TTF. After adjustment for surgical
      approach, the occurrence of complications was found to be associated with TTS,
      indicating that patients who experienced complications took longer before they
      could tolerate solid foods. CONCLUSIONS: In view of the importance of clinical
      care pathways in reducing medical expenditures from radical prostatectomy, the
      results of the current study may contribute to the further refining of these
      pathways by highlighting the differences and similarities among the variables
      affecting LOS as a function of surgical approach.

PMID- 10918177
TI  - Survival from head and neck cancer in Mumbai (Bombay), India.
AB  - BACKGROUND: Head and neck cancers, among the 10 most frequent cancers in the
      world, are common in regions with a high prevalence of tobacco and alcohol
      habits. They account for one-fourth of male and one-tenth of female cancers in
      India. The authors report and discuss the survival from these cancers in Mumbai
      (Bombay), India. METHODS: Follow-up information on 6311 head and neck cancer
      patients registered in the Bombay Population-Based Cancer Registry for the period
      1987-1991 was obtained by a variety of methods, including matching with death
      certificates from the Bombay vital statistics registration system,
      postal/telephone enquiries, home visits, and scrutiny of medical records. The
      survival for each case was determined as the duration between the date of
      incidence and the date of death or date of loss to follow-up or the closing date
      of the study (December 31, 1996). Cumulative observed and relative survival were
      calculated by the Hakulinen method. For comparison of results with other
      populations, age-standardized relative survival (ASRS) was calculated by directly
      standardizing age specific relative survival to the specific age distributions of
      the estimated global incidence of major cancers in 1985. The log rank test was
      used in univariate analysis to identify the potentially important prognostic
      variables. The variables showing statistical significance in univariate analysis
      were introduced stepwise into a Cox regression model to identify the independent
      predictors of survival. RESULTS: The 5-year relative survival rates were 74.5%
      for the lip, 42.7% for the anterior tongue, 25.5% for the posterior tongue, 45.1%
      for the mouth, 29.7% for the oropharynx, 38.7% for the nasopharynx, 29.1% for the
      hypopharynx, and 41.2% for the larynx. Age, marital status, religion, and site
      and clinical extent of disease emerged as independent predictors of survival. Age
      specific 5-year relative survival declined with advancing age. Single patients
      had a 20% excess risk of death compared with married patients. Those with cancers
      of the lip, mouth, nasopharynx, and larynx had a better prognosis than those with
      cancer at other sites. Those with regional spread of disease experienced a
      threefold increased risk of death, and those with distant metastasis experienced
      a sixfold excess risk. Less than one-fourth of cancers were localized in the
      organ of origin at diagnosis; 5-year survival for localized cancers ranged from
      52.9% to 80.2% depending on the subsite. CONCLUSIONS: There were significant
      variations in survival from cancer at individual sites within the head and neck
      region. Comparison with other populations revealed variations that seemed to be
      related to differences in detection and treatment. Tobacco and alcohol control
      measures and early detection linked with treatment are important measures to
      reduce mortality from head and neck cancer.

PMID- 10918176
TI  - Weekly 1-hour infusion of paclitaxel. Clinical feasibility and efficacy in
      patients with hormone-refractory prostate carcinoma.
AB  - BACKGROUND: Preclinically, paclitaxel given according to an intense bolus
      schedule has significant antitumor activity against human prostate carcinoma cell
      lines in SCID mice. The authors evaluated the feasibility and efficacy of weekly
      1-hour infusion of paclitaxel in patients with metastatic hormone-refractory
      prostate carcinoma (HRPC). METHODS: A total of 18 patients with progressive
      metastatic HRPC were enrolled. Patients had to have no prior chemotherapy.
      Paclitaxel was infused weekly at a dose of 150 mg/m(2) over 1 hour for 6 weeks
      every 8 weeks. RESULTS: Eighteen patients with a median age of 68.5 years and a
      median prostate specific antigen (PSA) level of 82 ng/mL (range, 2.17-3196 ng/mL)
      were enrolled. The median number of prior hormone treatments was 2, and 12
      patients on antiandrogens completed antiandrogen withdrawal. Ten of eighteen
      patients had bone-only metastasis and eight had metastasis to bone with lymph
      node and/or visceral metastasis. Seventeen patients received a total of 31 cycles
      (157 courses) and 1 patient refused chemotherapy. All patients were included in
      response evaluation. Of the 8 [corrected] patients with measurable disease, 4
      achieved a major response, with 1 complete response (in the lung) and 3 partial
      responses (1 in the liver and 2 in the lymph nodes). Seven of eighteen patients
      (39%) had a PSA decline of >/=50%. The major high grade toxicity was peripheral
      neuropathy, with 6 patients (35%) developing Grade 3 toxicity. CONCLUSIONS:
      Weekly 1-hour paclitaxel has activity in patients with HRPC. The major toxicity
      is peripheral neuropathy. The minimal myelosuppressive effects make a modified
      schedule (lower doses on the same schedule or a shorter schedule of the same
      dose) attractive for future combination chemotherapy trials.

PMID- 10918178
TI  - Telomerase activity in B-cell non-Hodgkin lymphoma.
AB  - BACKGROUND: Studies have shown telomerase activity to be present in some B-cell
      non-Hodgkin lymphomas (B-NHLs). However, no large studies have assayed telomerase
      activity in a systematic and quantitative manner. Furthermore, the relation
      between telomerase and proliferation suggested by in vitro studies has not been
      adequately tested in B-NHLs in vivo. This information is necessary to understand
      the relation between proliferation and telomerase and to predict the efficacy of
      antitelomerase drugs currently in development. METHODS: Eighteen benign biopsies
      and 111 B-NHLs of varying types were classified according to the revised European
      American classification of lymphoid neoplasms (REAL classification) and assayed
      for telomerase activity and proliferation index (PI). RESULTS: All B-NHLs
      contained telomerase activity except for low grade marginal zone B-cell lymphomas
      (MZBCLs) (96 of 111, 86%) (chi(2) 95.90, P < 0.001). Telomerase activity
      correlated with PI (r = 0.7536, r(2) = 0.5678, t = 10.51, P < 0.001) and showed a
      threshold whereby telomerase activity was not present below a PI of 9.2% (t =
      4.875, P < 0.001). CONCLUSIONS: The level of telomerase activity fell within
      characteristic ranges and generally correlated with the clinical aggressiveness
      of each B-NHL category. Low grade MZBCLs of extranodal, nodal, and splenic types
      were unique among the categories of B-NHL in lacking or containing very little
      telomerase activity. The association between telomerase activity and PI is
      evidence that telomerase is controlled in vivo along with the cell cycle and is
      not constitutively active in B-NHL. These data provide evidence that
      antitelomerase drugs may be efficacious in most types of B-NHL.

PMID- 10918179
TI  - Predicting sentinel and residual lymph node basin disease after sentinel lymph
      node biopsy for melanoma.
AB  - BACKGROUND: The selection of patients for sentinel lymph node biopsy (SNB) and
      selective lymphadenectomy for histologically positive sentinel lymph nodes (SLND)
      are areas of debate. The authors of the current study attempted to identify
      predictors of metastases to the sentinel and residual nonsentinel lymph nodes in
      patients with melanoma. METHODS: The Indiana University Interdisciplinary
      Melanoma Program computerized database was queried to identify all patients who
      underwent SNB for clinically localized cutaneous melanoma. Demographic, surgical,
      and histopathologic data were recorded. Univariate and multivariate logistic
      regression analyses were performed to identify associations with SNB and
      nonsentinel lymph node positivity. Classification tree and logistic procedures
      were performed to identify the ideal tumor thickness cutpoint at which to perform
      SNB. RESULTS: Two hundred seventy-five SNB procedures were performed to stage 348
      regional lymph node basins for occult metastases from melanoma. Of the 275
      melanomas, 54 (19.6%) had a positive SNB, as did 58 of 348 basins (16.7%).
      Classification and logistic regression analysis identified a Breslow depth of
      1.25 mm to be the most significant cutpoint for SNB positivity (odds ratio 8.
      8:1; P = 0.0001). By multivariate analyses, a Breslow thickness cutpoint >/= 1.25
      mm (P = 0.0002), ulceration (P = 0.005), and high mitotic index (> 5 mitoses/high
      power field; P = 0.04) were significant predictors of SNB results. SLND was
      performed in 53 SNB positive patients, 15 of whom (28.3%) had at least 1
      additional positive lymph node. SLND positivity was noted across a wide range of
      primary tumor characteristics and was associated significantly with multiple
      positive SN, but not with any other variable. SNB result correlated significantly
      with disease free and overall survival. CONCLUSIONS: Patients with a Breslow
      tumor thickness >/= 1. 25 mm, ulceration, and high mitotic index are most likely
      to have positive SNB results. SLND is recommended for all patients after positive
      SNB because it is difficult to identify patients with residual lymph node
      disease.

PMID- 10918180
TI  - Epstein-Barr virus infection in salivary gland tumors in children and young
      adults.
AB  - BACKGROUND: Epstein-Barr virus (EBV) infection has been implicated in the
      pathogenesis of certain subtypes of salivary gland tumors in the adult
      population. However, to the authors' knowledge its role in pediatric salivary
      gland tumors, a rare disease, has not been explored previously. METHODS: Thirteen
      cases of primary tumors of the salivary gland occurring in children were
      retrieved from the tumor registry at the St. Jude Children's Research Hospital in
      Memphis, Tennessee. Clinical data were analyzed from the medical records and
      formalin fixed, paraffin embedded tumor tissues were examined by the in situ
      hybridization (ISH) technique for the presence of latent EBV infection. RESULTS:
      Twelve of 13 tumors originated from the parotid gland and 1 originated from the
      submandibular gland. Mucoepidermoid carcinoma was the predominant tumor type; it
      was observed in seven patients, rhabdomyosarcoma was the diagnosis in three
      patients, acinic cell carcinoma was noted in two patients, and malignant fibrous
      histiocytoma was diagnosed in one patient. The ages of the patients ranged from
      4.1-29.2 years, with a median age of 11 years. The outcome was excellent with all
      patients alive and free of disease at the time of last follow-up. The ISH tested
      negative in all tumor samples. CONCLUSIONS: Based on the results of the current
      study, EBV infection does not appear to play a major role in the pathogenesis of
      pediatric salivary gland tumors.

PMID- 10918181
TI  - Posttransplant Epstein-Barr virus-associated myogenic tumors involving bone.
AB  - BACKGROUND: Epstein-Barr virus (EBV)-associated myogenic tumors in
      immunocompromised patients were recently recognized, but their biologic behavior
      remains only partially understood. Although observations so far have permitted
      the recognition of similarities between posttransplant myogenic tumors and
      posttransplant lymphoproliferative disorders (PTLD), the number of reports are
      still few, and new experiences continue to be informative. METHODS: The authors
      describe what they believe is the first example of posttransplant EBV-associated
      myogenic tumor involving bone, which is also remarkable for its multicentric
      symmetric limb distribution. Immunohistochemistry of tumor cells for myogenic
      antigens (desmin and smooth muscle actin), EBV antigens (latency proteins latent
      membrane protein-1 [LMP-1], Epstein-Barr nuclear antigen-2 [EBNA-2], and ZEBRA),
      p53, and bcl-2 was examined by standard avidin-biotin-peroxidase complex methods.
      Molecular techniques investigated in situ hybridization for Epstein-Barr virus
      encoded messenger RNAs (EBERs) and single-strand conformation polymorphism
      analysis for p53 mutation. RESULTS: Although the biologic behavior of this tumor
      was uncertain, the reduction of immunosuppression arrested tumor growth for 5
      years, at the expense of some loss in renal function. The occurrence of episodes
      of acute cellular rejection required pulse therapy, resulting in the appearance
      of new lesions in both liver and lungs. Despite these complications, a balance
      between control of this multicentric tumor growth and allograft survival has been
      maintained for 8 years. CONCLUSIONS: To the authors' knowledge, this example of
      posttransplant myogenic tumor is the first described in the bone. It shows
      partial response to immunomodulation with persistent tumor, with prolonged
      survival of the renal allograft.

PMID- 10918183
TI  - Malignant melanoma in patients with multiple endocrine neoplasia type 1 and
      involvement of the MEN1 gene in sporadic melanoma.
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is a familial cancer syndrome
      associated primarily with endocrine tumors of the parathyroids, enteropancreas
      and anterior pituitary. However, tumors of mesenchymal origin such as
      angiofibroma and collagenoma of the skin have also been associated with the
      syndrome. This highlights the possibility of an association between MEN 1 and
      some other types of tumors. Here we report 7 cases of primary malignant melanoma
      occurring in 7 MEN 1 families, all patients exhibiting classic features of MEN 1.
      Based on these findings and the previous implication of multiple melanoma tumor
      suppressor(s) in 11q, including the MEN1 region, we have investigated the
      involvement of the MEN1 gene in melanoma tumorigenesis. Mutation analysis was
      performed on a panel of 39 sporadic metastatic melanomas, 13 melanoma cell lines
      and 20 melanoma families without CDKN2A or CDK4 germline mutations. In addition,
      19 sporadic metastatic tumors were screened for loss of heterozygosity (LOH) in
      11q13. LOH was detected in 6 tumors (32%), and in 4 of the tumors the pattern of
      LOH suggested that the deletion included the MEN1 gene locus. A novel somatic
      nonsense mutation in exon 7 (Q349X) was identified in 1 sporadic tumor which also
      showed loss of the wild-type allele. We conclude that the MEN1 gene plays a role
      in the tumorigenesis of a small subgroup of melanoma.

PMID- 10918184
TI  - Expression of cell cycle-regulatory proteins rb, p16/MTS1, p27/KIP1, p21/WAF1,
      cyclin D1 and cyclin E in breast cancer: correlations with expression of
      activating protein-1 family members.
AB  - The activating protein-1 (AP-1) complex is a mitogen-activated composite
      transcription factor that leads to activation of various target genes and
      enhanced proliferation of many cells after stimulation by TPA, EGF, serum, etc.
      The molecular mechanism of cell-cycle activation by AP-1 complexes remains
      unclear. Therefore, we studied protein expression of 6 cell cycle-regulatory
      proteins (Rb, p16, p21, p27, cyclin D1, and cyclin E) in protein extracts from 53
      breast cancer samples and 4 mammary cell lines and correlated the data with
      expression of the 7 AP-1 family members (c-jun, junB, junD, c-fos, fosB, fra-1,
      and fra-2) as determined in a previous study. After Western blot analysis, we
      found significant associations between members of both groups: whereas c-jun was
      associated with Rb expression (p = 0.002), strong junD and c-fos expression
      correlated with high cyclin E reactivity (p = 0.017 and p = 0.013, respectively).
      Over-expression of fosB was found mainly in tumors with strong Rb (p = 0.013) and
      weak p16 (p = 0.004) expression. Fra-1 expression was significantly associated
      with p16 and cyclin E over-expression, whereas fra-2 results correlated with both
      cyclin D1 and cyclin E. These results point to direct or indirect activation of
      some cell cycle-regulatory proteins by AP-1 complexes. In addition, our data
      suggest differential regulation of cell cycle-stimulating and -inhibiting factors
      depending on the abundance of single AP-1 family members.

PMID- 10918185
TI  - Negative regulation of Fas-mediated apoptosis by FAP-1 in human cancer cells.
AB  - FAP-1 (Fas-associated phosphatase-1) was previously identified as a protein that
      associates with a negative regulatory domain (C-terminal 15 amino acids) of Fas
      using the yeast 2-hybrid system. Functional analysis indicated that FAP-1
      expression correlates with resistance to Fas-induced apoptosis in human cancer
      cells. We first generated anti-FAP-1 polyclonal antibody and confirmed the
      interaction of FAP-1 and Fas in vivo. FAP-1 interacted with wild-type, but not
      mutant, Fas (tPLV) in 293T cells after transfecting FAP-1 and Fas or its mutant.
      To investigate the functional role of FAP-1 in Fas-mediated signal transduction,
      we established stable transfectants of FAP-1 in 3 human cancer cell lines.
      Apoptosis assays demonstrated that cancer cells over-expressing FAP-1 increased
      the resistance to Fas-induced apoptosis by the anti-Fas antibody CH-11 in
      contrast with the wild types or the vector-transfected cells. In addition, FAP-1
      regulated the activity of both caspases 3 and 8. Our data indicate a functional
      role for FAP-1 as a negative regulator of Fas-mediated apoptosis in human cancer
      cells and suggest that an additional signal-transducing molecule may be required
      for complete suppression of Fas-mediated apoptosis.

PMID- 10918186
TI  - Potentiation of metastasis by cell surface sialomucin complex (rat MUC4), a
      multifunctional anti-adhesive glycoprotein.
AB  - Sialomucin complex (SMC), a rat homologue of the human mucin MUC4, is a large
      membrane-bound mucin complex, originally isolated from highly metastatic ascites
      13762 mammary adenocarcinoma cells. When overexpressed, SMC exerts potent anti
      adhesive effects, which sterically disrupt molecular interactions for cell-cell
      and cell-ECM adhesions. SMC similarly suppresses anti-tumor immunity by
      inhibition of interactions between cytotoxic lymphocytes and target tumor cells.
      Previously, recombinant cDNAs for SMC were transfected and inducibly expressed in
      A375 human melanoma cells using a tetracycline-responsive expression system. In
      the current studies, we investigated the role of MUC4/SMC in tumor metastasis by
      regulating SMC expression of tumor transplants in vivo. Intravenous injection of
      SMC-overexpressing cells resulted in substantially greater lung metastasis than
      injection of SMC-repressed cells. Injection of SMC-overexpressing cells followed
      by in vivo downregulation of SMC did not lower the frequency of lung metastasis.
      Growth of the micrometastatic lesions was the same for all 3 cases in short-term
      (3-week) assays. Further, subcutaneous injection of A375 cells followed by in
      vivo induction of SMC overexpression within the solid tumor resulted in
      spontaneous distant metastasis. These studies suggest that SMC potentiates
      metastasis by contributing to the establishment of metastatic foci. These studies
      directly demonstrate for the first time that tumor metastasis can be modulated by
      the regulation of MUC4/SMC expression.

PMID- 10918187
TI  - Expression of c-erbB receptors, heregulin and oestrogen receptor in human breast
      cell lines.
AB  - Members of the c-erbB family have been implicated in poor prognosis in breast
      cancer. Given the propensity for heterodimerisation within the erbB family, the
      pattern of co-expression of these receptors is likely to be as functionally
      important as aberrant expression of any given receptor alone. Therefore, the
      patterns of expression of the receptors, epidermal growth factor receptor (EGF
      R), c-erbB-2, c-erbB-3, c-erbB-4, and one of the erbB ligands, heregulin (HRG),
      were examined in normal and malignant breast cell lines and compared with
      expression of oestrogen receptor (ER), a classical indicator of good prognosis.
      There was an inverse correlation between ER and EGF-R mRNA levels, as previously
      described, but no correlation between either of these receptors and c-erbB-2. c
      erbB-3 expression was positively correlated with ER. In contrast, HRG expression
      was inversely related to ER. Expression of antisense-ER resulted in increased EGF
      R mRNA, demonstrating a functional link between the expression of these 2 genes,
      however, there was no significant change in c-erbB-2 or c-erbB-3 mRNA, suggesting
      that ER is not directly involved in control of expression of these genes. A
      comparison of individual erbB receptors and HRG revealed that the majority of
      lines expressing increased levels of c-erbB-2 also expressed elevated levels of c
      erbB-3 mRNA, and none of the cell lines that expressed both c-erbB-2 and either c
      erbB-3 or c-erbB-4 expressed the ligand HRG. In summary, the levels of expression
      of c-erbB-1, -2, -3, and -4 varied in this series of breast cell lines, and the
      pattern of expression and the relationship of each growth factor receptor to the
      expression of ER was quite distinct. The lack of expression of HRG in cell lines
      that express receptors may be indicative of paracrine interactions between erbB
      ligands and their cognate receptors and may suggest that the ligand and receptors
      are expressed in different subtypes of breast epithelial cells from which the
      cell lines are derived.

PMID- 10918188
TI  - Phosphorylation of the cytoplasmic domain of the MUC1 mucin correlates with
      changes in cell-cell adhesion.
AB  - The MUC1 epithelial mucin is expressed by glandular epithelial cells and is often
      highly expressed and associated with poor prognosis in adenocarcinomas. Tyrosine
      phosphorylation of the highly conserved cytoplasmic tail of MUC1 (MUC1-CT) has
      been demonstrated in MUC1 transfected cells and in one breast cancer cell line.
      In addition, associations between MUC1 and secondary signalling molecules have
      been demonstrated in breast cancer cell lines. MUC1 clearly plays a role in
      intracellular signalling, since we were able to demonstrate tyrosine
      phosphorylation of the MUC1-CT in breast and ovarian cancer cell lines and in
      primary cultures of serous ovarian cancers. We were unable to modulate MUC1-CT
      phosphorylation using conditioned media from cell lines showing the highest
      levels of signalling. However, in several breast and ovarian cancer cell lines,
      we clearly showed the highest levels of MUC1-CT tyrosine phosphorylation occurred
      during recolonisation of culture dishes or in low-density adherent cultures. We
      now hypothesise that phosphorylation changes may reflect either involvement of
      MUC1 in cell motility or a redistribution of MUC1 in the membrane during the
      course of cell-cell adhesion.

PMID- 10918189
TI  - A pilot study investigating the role of NAT1 and NAT2 polymorphisms in gastric
      adenocarcinoma.
AB  - In humans, aromatic and heterocyclic amine carcinogens may be acetylated by the
      expression products of either of the N-acetyltransferase genes, NAT1 or NAT2.
      This conjugation reaction can result in either activation or detoxication of
      these carcinogens depending on the tissue involved. Recent studies suggest that
      polymorphisms in NAT1 or NAT2 may modulate cancer risk. To determine if genetic
      differences in NAT1 and NAT2 could alter risk of gastric cancer, we tested for
      the presence of polymorphic N-acetyltransferase alleles (both NAT1 and NAT2) in a
      preliminary study of 94 gastric adenocarcinoma patients and 112 control subjects
      from North Staffordshire, England. We used established PCR protocols to genotype
      for NAT2 and NAT1 alleles (NAT2*4, NAT2*5, NAT2*6, NAT2*7, NAT2*14; NAT1*3, NAT1*
      4, NAT1*10, and NAT1*11), and implemented an oligonucleotide ligation assay (OLA)
      to test for low-activity NAT1 alleles [NAT1*14 (G560A), NAT1*15 (C559T), and
      NAT1*17 (C190T)]. No significant increased risk was observed for NAT2 acetylation
      genotypes. However, among all cases, we found that individuals inheriting a
      variant NAT1 allele, NAT1*10, have a significantly elevated risk for gastric
      cancer (OR = 2.2, 95% CI 1. 2-3.9, P < 0.01). Interestingly, the risk observed
      for NAT1*10 appears to be solely associated with advanced-stage tumors (OR = 4.8,
      P < 0.001), suggesting a possible role in progression to advanced disease. This
      preliminary finding needs confirmation in a larger, detailed epidemiological
      study.

PMID- 10918190
TI  - Genetic alterations in gastric cancer cell lines and their original tissues.
AB  - To investigate the genetic changes that occur during establishment of gastric
      cancer cell lines, 4 gastric cancer cell lines and their original tumor tissues
      were examined for microsatellite instability (MSI), loss of heterozygosity (LOH),
      and p53 mutation. MSI status did not change during the establishment, though the
      cell lines gained frameshift mutation in some of the genes with polytract coding
      sequences. There was no difference in p53 mutation between the cell lines and the
      original tumors. The frequency of LOH was similar between the cell lines and each
      original tumor, in the range 30.8% to 85.7%. The difference in the LOH results
      between the cell lines and the original tumors was not greater than the
      difference between the different areas of the original tumors. The above results
      suggested that most of the genetic alterations, such as MSI, LOH, and p53 gene
      mutation, were sustained during the establishment of gastric cancer cell lines.
      Minor genetic differences between original tumor tissues and cancer cell lines
      could be explained as a tumor heterogeneity because separate areas of the
      original tumor tissues manifest similar variations.

PMID- 10918191
TI  - Impaired BAX protein expression in breast cancer: mutational analysis of the BAX
      and the p53 gene.
AB  - We have previously shown that the pro-apoptotic BAX protein is differentially
      expressed in breast cancer and in other epithelial tumors. In this line, a
      reduced BAX protein expression is a negative prognostic factor in various
      carcinomas including breast cancer. For p53, a trancriptional activator of BAX in
      apoptosis, mutations in the coding sequence were shown to modulate BAX protein
      expression in cell line models on the transcriptional level. We therefore
      investigated the BAX gene in 68 breast cancer specimens for the presence of
      mutations in the coding sequence by single-strand conformation polymorphism
      (SSCP)-PCR and direct sequencing. The expression of BAX protein was assessed by
      immunohistochemistry. In addition, we screened for mutations in the exons 5-8 of
      the p53 gene by SSCP-PCR to assess whether mutations in the DNA-binding domain of
      this upstream regulator of BAX gene transcription are responsible for differences
      in BAX protein expression. As previously observed, BAX was differentially
      expressed in the breast cancer samples, but no mutations in the coding sequence
      of the BAX gene were found besides a polymorphism in exon 6 at the position 552
      (G->A) and additional intronic polymorphisms. In contrast, we identified 16 of 68
      (23.5%) tumors to bear mutations in the p53 gene. In the subset of BAX-expressing
      tumors, the mutational inactivation of p53 did result in a reduced BAX protein
      expression (Fisher exact test, p = 0. 047). Nevertheless, we identified a subset
      of BAX-negative tumors lacking BAX or p53 mutations. Thus, additional, not yet
      identified regulators, apart from p53, appear to be involved in the regulation of
      BAX protein expression.

PMID- 10918192
TI  - Allelic losses demonstrate monoclonality of multifocal bladder tumors.
AB  - The clonality of multifocal bladder tumors has been studied over the years with
      some controversial results. We have examined 5 patients with 2-11 low-grade
      superficial multifocal bladder tumors for loss of heterozygosity (LOH) at 87 loci
      on 9 chromosomes. When LOH was detected at a given marker, the tumors
      consistently showed deletion of a specific allele, suggesting the monoclonality
      of the patients' tumors. No allelic imbalancies were detected between
      heterozygote alleles, and the allelic losses were only slightly biased toward the
      loss of the shorter alleles as the overall ratio was 0.48 +/- 0.10 (0.50 for
      nonbiased). We calculated the probabilities for monoclonality using binomial
      distribution. The use of multiple tumors with multiple microsatellite markers
      gives high statistical power for the calculation. The combined probabilities for
      monoclonality varied from 0.984 to (1-4 x 10(-28)). Thus, in most (4/5) cases,
      the probability for polyclonality was <2 x 10(-16). These results demonstrate
      that superficial multifocal bladder tumors are most likely of monoclonal origin.

PMID- 10918194
TI  - Decrease of human T-cell lymphotropic virus type I prevalence and low incidence
      among pregnant women from a high endemic ethnic group in French Guiana.
AB  - To assess the prevalence and incidence of human T-cell lymphotropic virus type I
      (HTLV-I), 4,234 pregnant women of different ethnic origins were tested before
      each delivery between 1991 and 1997 in a high HTLV-I endemic area of French
      Guiana. HTLV-I was significantly more prevalent among ethnic groups of African
      descent as the Noir-Marrons (4.8%, 95% confidence interval [CI]: 4.0-5.6) and
      Haitians (5%, 95% CI 1.6-8.4). An age dependence of HTLV-I seroprevalence was
      observed. The mean age of Noir-Marron HTLV-I seronegative women was lower than
      for HTLV-I seropositive women (24. 7 vs. 28.6, p < 0.001). A decline in HTLV-I
      seroprevalence was observed, particularly in the Noir-Marron younger than 21
      years old (p = 0.04). For five HTLV-I seroconversions observed, the incidence per
      100 women-years in the Noir-Marron group was 0.19 (95% CI 0.02-0. 35) for all
      women, 0.32 in those 25 years old or younger (95% CI 0-0. 64), and 0.07 in those
      older than 25 years (95% CI 0-0.2). This observation was inconsistent with HTLV-I
      seroprevalence observed for those 25 years old or younger (2.8%) and those older
      than 25 (8.3%). These data demonstrate, for the first time outside Japan, a birth
      cohort effect for HTLV-I in a highly endemic ethnic group.

PMID- 10918193
TI  - P53 polymorphism in codon 72 and risk of human papillomavirus-induced cervical
      cancer: effect of inter-laboratory variation.
AB  - An association between codon-72 p53 polymorphism and risk of human papillomavirus
      (HPV)-induced cervical cancer has been found recently, but it has been difficult
      to replicate. In this study, we assess the impact of inter-laboratory variation
      in p53 genotyping on the validity of the proposed association. DNA specimens were
      randomly selected from 54 invasive, squamous cell carcinoma cases, 52 HPV
      negative, and 39 HPV-positive controls from a previous case-control study in
      Brazil. Codon-72 polymorphism was blindly analyzed in three different
      laboratories. We calculated age- and race-adjusted odds ratios (OR) and 95%
      confidence intervals (CI) using logistic regression for gauging the association
      between p53 polymorphism and cervical cancer risk. The proportions of the
      Arg/Arg, Arg/Pro, and Pro/Pro genotypes varied substantially among laboratories
      with Kappa coefficients in the 0.49-0.63 range. When disagreement between labs
      was allowed, the OR for the Arg/Arg genotype, compared to other forms, was as low
      as 1.5 (95% CI: 0.5-3. 9). In contrast, the OR increased to 8.0 (95% CI: 2.3
      28.5) after exclusion of discordant genotypes. Restricting the comparison to HPV
      positive controls increased the magnitude of the relation appreciably. After
      exclusion of all discordant diagnoses, the OR was 21.5 (95% CI: 3.4-137.8),
      whereas with disagreed genotypes the association was not significant (OR = 2.9,
      95% CI: 0.7-11.9). Homozygous codon-72 p53-Arg apparently confers a higher
      susceptibility to HPV-associated cervical tumorigenesis. However, exposure
      misclassification consequent to inter-laboratory variation in protocols may
      affect the ability to detect the association.

PMID- 10918195
TI  - B7-1, IFN gamma and anti-CTLA-4 co-operate to prevent T-cell tolerization during
      immunotherapy against a murine T-lymphoma.
AB  - We previously reported on a murine T lymphoma cell line, BW-Sp3, with inherent
      immunogenicity. BW-Sp3 tumors can elicit an anti-tumor CD8(+) CTL response
      capable of mediating a regression of subcutaneous tumors. However, this immune
      response is inadequate to eliminate cancer cells completely in a significant
      percentage of the recipients, resulting in progressing tumors. In this tumor
      model, tumor progression correlated with a tolerization of tumor-reactive T cells
      and cellular immunotherapy of tumor bearing animals, with or without B7-mediated
      costimulation, even increased tumor progression (Raes et al, 1998). In the
      present study, we investigated whether the co-expression of IFN gamma, together
      with B7-1, could have beneficial effects on immunotherapy. Although immunotherapy
      with IFN gamma and B7-1 single transfectants tended to tolerize anti-tumor T
      cells and consequently increased tumor growth, the B7-1/IFN gamma double
      transfectants resulted in a more beneficial outcome. This phenomenon correlated
      with an increased CTL-inducing potential of the double transfectants. Secondly,
      we wondered whether CTLA-4 signalling was involved in the down-regulation of the
      anti-tumor response. Indeed, when immunotherapy was provided along with anti-CTLA
      4, the protection by B71/IFN gamma double transfectants was further improved and
      the tumor-promoting effect of BW-Sp3(B7-1) was compensated for. Our results
      indicate that B7-1, IFN gamma and the blockade of CTLA-4 cooperate to tilt the
      balance in favour of tumor elimination, while either factor alone fails to do so
      or even promotes tumor growth.

PMID- 10918196
TI  - The 17-1A antigen is expressed on primary, metastatic and disseminated non-small
      cell lung carcinoma cells.
AB  - In view of the high incidence of early distant tumor relapses in apparently
      completely resected (R0, M0) non-small cell lung cancer (NSCLC), there is a need
      for an adjuvant therapy. Considering the low tumor burden in these patients, an
      adjuvant therapy with monoclonal antibodies (i.e., the 17-1A MAb) might be
      appropriate. The purpose of our study was to test whether the 17-1A antigen is
      expressed on primary and metastatic NSCLC carcinoma cells. Using
      immunohistochemistry, the expression of 17-1A was analysed in primary tumors (n =
      60) and in lymph node metastases (n = 7) of patients with NSCLC. Additionally, we
      investigated in 6 patients the expression of 17-1A on disseminated tumor cells in
      the bone marrow, which were detected by the pan-cytokeratin MAb A45-B/B3 using a
      double-labeling technique. The 17-1A antigen was homogeneously expressed in 47
      (78.3%) out of 60 primary NSCLCs. The expression of 17-1A was independent from
      the tumor histology, the grade of differentiation, and other clinicopathological
      parameters (ploidy status, TNM-stage). Lymph node metastases were positive in 4
      (57.4%) out of 7 cases. The double-labeling experiments demonstrated that 17-1A
      is coexpressed on disseminated tumor cells in the bone marrow in 5 (83%) out of 6
      patients. The 17-1A antigen is expressed on the majority of primary, metastatic,
      and disseminated NSCLC cells. Patients with 17-1A-positive tumors might benefit
      from an adjuvant therapy with MAb 17-1A after completely resected NSCLC.

PMID- 10918197
TI  - A HER2/NEU-derived peptide, a K(d)-restricted murine tumor rejection antigen,
      induces HER2-specific HLA-A2402-restricted CD8(+) cytotoxic T lymphocytes.
AB  - We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from
      murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T
      lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells
      pulsed with HER2p780 peptide, entirely common to murine and human HER2,
      suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2
      expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA
      could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2
      expressing cancer cells can process and present the cognate peptide in the
      context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor
      motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in
      HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2
      expressing cancer cell lines were established from peripheral blood lymphocytes
      with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic
      cells as well as peripheral blood mononuclear cells. Detailed analysis of their
      specificity revealed that the cytotoxicity of CTL clones is specific for the
      cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is
      a unique peptide that may function as a tumor rejection antigen peptide in HLA
      A2402 individuals, as it was directly proven here to function in a murine tumor
      system.

PMID- 10918199
TI  - Murine granulocytes control human tumor growth in SCID mice.
AB  - Severe combined immunodeficient (SCID) mice generally do not reject allogeneic or
      xenogeneic organ grafts and represent a unique model for investigating in vivo
      the behaviour of both normal and neoplastic human cells. However, cells from
      human primary tumors often do not grow in SCID mice. We have previously shown
      that the major reaction of SCID mice to the engraftment of human peripheral blood
      leukocytes is a massive granulocyte recruitment into the site of transplantation.
      In this study, we have investigated the role of murine granulocytes in the
      control of human tumor cell growth in SCID mice. We report here that murine
      granulocytes infiltrate and delimit the human tumor mass and that treatment of
      SCID mice with anti-murine granulocyte antibody markedly improves the growth of
      human tumor cell lines of different origin through suppression of the host
      granulocyte reaction. This finding provides a new tool for improving the human
      tumor take in SCID mice, thus opening new perspectives for a practical in vivo
      preclinical test of anti-tumor strategies. Moreover, this study, even with the
      limits of the known natural reaction against xenotransplants, further supports
      the importance of granulocytes in the control of tumor take and growth.

PMID- 10918198
TI  - A3--a novel colon and pancreatic cancer reactive antibody from a primate phage
      library selected using intact tumour cells.
AB  - The identification of novel tumour-associated antigens (TAAs) is pivotal for
      progression in the fields of tumour immunotherapy and diagnosis. In the present
      study, we have developed, based on flow cytometric evaluation and use of a mini
      library composed of specific antibody clones linked to different antibiotic
      resistance markers, methods for positive and subtractive selection of phage
      antibodies employing intact cells as the antigen source. An scFv phage library
      (2.7 x 10(7)) was constructed from a primate (Macaca fascicularis) immunised with
      pooled human colon carcinomas. This library was selected for 3 rounds by binding
      to Colo 205 colon adenocarcinoma cells and proteolytic elution followed by phage
      amplification. Several antibodies reactive with colon carcinomas and with
      restricted reactivity to a few epithelial normal tissues were identified by
      immunohistochemistry. One clone, A3 scFv, recognised an epitope that was
      homogeneously expressed in 11/11 of colon and 4/4 pancreatic carcinomas studied
      and in normal tissue restricted to subtypes of epithelia in the gastrointestinal
      tract. The A3 scFv had an apparent overall affinity approximately 100-fold higher
      than an A3 Fab, suggesting binding of scFv homodimers. The cell surface density
      of the A3 epitope, calculated on the basis of Fab binding, was exceptionally
      high, approaching 3 million per cell. We also demonstrate efficient T-cell
      mediated killing of colon cancer cells coated with A3 scFv fused to the low MHC
      class II binding superantigen mutant SEA(D227A). The identified A3 molecule thus
      represents a TAA with properties that suggest its use for immunotherapy of colon
      and pancreatic cancer.

PMID- 10918200
TI  - Gene transfer of a secretable form of IL-15 in murine adenocarcinoma cells:
      effects on tumorigenicity, metastatic potential and immune response.
AB  - IL-15 is an immunostimulatory cytokine with IL-2-like activities. To exploit the
      potential role of IL-15 in cancer immuno-/gene therapy, we engineered murine TS/A
      cells with different IL-15 cDNA constructs. Significant IL-15 secretion was
      achieved only by the use of a modified cDNA encoding for an IL-15 pre-protein
      bearing the IgK light chain signal peptide. Different TS/A clones (TS/A IL-15 C6,
      C23, C29) producing 390 to 1,600 pg/ml biologically active IL-15 showed reduced
      tumorigenicity when implanted s.c. in syngeneic mice and significantly reduced
      metastatic potential by i.v. injection. Tumorigenicity of s.c. TS/A IL-15 was
      restored in animals depleted of CD8(+) lymphocytes or of natural killer cells and
      partially in CD4(+)-depleted mice. TS/A IL-15 cells displayed a significantly
      reduced growth rate by s.c. implant in nude mice. Also, >50% syngeneic animals
      rejecting TS/A IL-15 were resistant to a subsequent rechallenge with wild-type
      tumor (TS/Apc), indicating induction of protective immunity against TS/A tumor
      associated antigens (TAAs). Cytolytic T lymphocyte (CTL) activity, specifically
      inhibited by anti-CD3 antibodies, was inducible in the splenocytes of TS/A IL-15
      immunized animals by mixed lymphocyte/tumor culture (MLTC), and IFN-gamma was
      released in the supernatant of MLTC, mainly by CD8(+) cells. Immunohistochemistry
      of the TS/A IL-15 tumor area revealed the presence of an inflammatory infiltrate
      with predominant natural killer, macrophage, and granulocyte components and
      expression of IFN-gamma as a distinctive secondary cytokine. Use of TS/A IL-15
      mitomycin-treated cells for therapeutic vaccination in experimental TS/A
      metastasis was effective in 60% of animals treated; these animals showed no
      metastatic tumor growth.

PMID- 10918201
TI  - Bcl-xl antisense treatment induces apoptosis in breast carcinoma cells.
AB  - Upregulated expression of bcl-xL is involved in the initiation and progression of
      breast cancer by inhibiting tumor cell apoptosis. Here we describe the use of the
      2;-O-methoxy-ethoxy antisense oligonucleotide 4259 targeting nucleotides 687-706
      of the bcl-xL mRNA, a sequence that does not occur in the pro-apoptotic bcl-xS
      transcript, to restore apoptosis in estrogen-dependent and independent breast
      carcinoma cells. The antisense effect of oligonucleotide 4259 was examined on the
      mRNA and protein level using real-time PCR and Western blot analysis,
      respectively, and the induction of cell death was investigated in viability and
      apoptosis assays. Treatment of MCF7 cells with oligonucleotide 4259 at a
      concentration of 600 nM for 20 hr decreased bcl-xL mRNA and protein levels by
      more than 80% and 50%, respectively. This resulted in the induction of apoptosis
      characterized by mitochondrial cytochrome c release, decrease of mitochondrial
      transmembrane potential, and the appearance of condensed nuclei in approximately
      40% of cells. Moreover, oligonucleotide 4259 efficiently downregulated bcl-xL
      expression and decreased cell growth in the breast carcinoma cell lines T-47D, ZR
      75-1, and MDA-MB-231. Our data emphasize the importance of bcl-xL as a survival
      factor for breast carcinoma cells and suggest that oligonucleotide 4259 deserves
      further investigations for use in breast cancer therapy.

PMID- 10918202
TI  - Long-term oral contraceptive use increases breast cancer risk in women over 55
      years of age: the DOM cohort.
AB  - The role of past oral contraceptive use in the development of breast cancer is
      unclear, particularly in postmenopausal women. The authors investigated this
      relationship among pre- and postmenopausal middle-aged women in a nested case
      control study within the population-based DOM cohort, Utrecht, the Netherlands.
      Among a total population of 12,184 women followed up for an average of 7.5 years,
      309 breast cancer cases aged 42 to 63 years, diagnosed from November 1982 through
      May 1996, and 610 controls were examined. Overall, duration of oral contraceptive
      use was not clearly related to breast cancer. In women older than 55 years,
      however, oral contraceptive use for more than 10 years was associated with a 2
      fold increased risk of breast cancer (odds ratio (OR) 2.1, 95% confidence
      interval (CI) 1.1-4.0). We conclude that long duration of oral contraceptive use
      increases the risk of breast cancer in women over 55 years of age but not in
      younger women.

PMID- 10918203
TI  - Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic
      potential.
AB  - Flavonoids are a class of polyphenolic compounds widely distributed in the plant
      kingdom, which display a variety of biological activities, including
      chemoprevention and tumor growth inhibition. Our aim was to investigate the
      effects of several polyphenols on the growth and metastatic potential of B16-BL6
      melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (
      )-epigallocathechin-3-gallate (EGCG), resveratrol, and the anti-estrogen
      tamoxifen, at the time of i.m. injection of B16-BL6 cells into syngeneic mice,
      resulted in a significant, dose-dependent delay of tumor growth, without
      toxicity. The relative descending order of potency was EGCG > apigenin =
      quercetin = tamoxifen > resveratrol > control. Furthermore, polyphenols
      significantly potentiated the inhibitory effect of a non-toxic dose of cisplatin.
      When tested for the ability to inhibit lung colonization, quercetin, apigenin,
      and tamoxifen (but not EGCG or resveratrol) significantly decreased the number of
      B16-BL6 colonies in the lungs in a dose-dependent manner, with quercetin and
      apigenin being more effective than tamoxifen. Interestingly, quercetin, apigenin,
      and tamoxifen (but not EGCG or resveratrol) significantly decreased the invasion
      of B16-BL6 cells in vitro, with quercetin and apigenin being more effective than
      tamoxifen. This suggests that anti-invasive activity is one of the mechanisms
      underlying inhibition of lung colonization by quercetin and apigenin. In
      conclusion, quercetin and apigenin inhibit melanoma growth and invasive and
      metastatic potential; therefore, they may constitute a valuable tool in the
      combination therapy of metastatic melanoma.

PMID- 10918204
TI  - Time course of fenretinide-induced modulation of circulating insulin-like growth
      factor (IGF)-i, IGF-II and IGFBP-3 in a bladder cancer chemoprevention trial.
AB  - The insulin-like growth factor (IGF) system is widely involved in human
      carcinogenesis. A significant association between high circulating IGF-I
      concentrations and an increased risk of lung, colon, prostate and pre-menopausal
      breast cancer has recently been reported. Lowering plasma IGF-I may thus
      represent an attractive strategy to be pursued for chemopreventive purposes. We
      have previously shown that the synthetic retinoid fenretinide (4-HPR) lowers
      plasma IGF-I in pre-menopausal breast cancer patients. We investigated the effect
      of fenretinide on circulating IGF-I, IGF-II and IGFBP-3 measured at yearly
      intervals during the 2-year treatment period and one year after treatment
      discontinuation in a predominantly male population of patients with superficial
      bladder cancer. Repeated measures analysis, after adjustment for age, body mass
      index (BMI) and year of study, showed a significant effect of fenretinide on IGF
      I levels, which were further lowered after the second year of treatment and only
      partially recovered after drug discontinuation. Differently from breast cancer
      patients, the effect of fenretinide was not modified by age. No significant
      effect was evident on IGFBP-3, IGF-II and the IGF-I+IGF-II/IGFBP-3 molar ratio,
      expressing the tissue availability of the mitogenic peptides, although IGF-II and
      the molar ratio were lowered by treatment by an overall mean of 16% and 15%,
      respectively. Given the increasingly recognized importance of circulating IGFs in
      the pathogenesis of different solid tumors, our findings strengthen the rationale
      for studying fenretinide as a chemopreventive agent.

PMID- 10918205
TI  - Efficacy of ionizing radiation combined with adenoviral p53 therapy in EBV
      positive nasopharyngeal carcinoma.

PMID- 10918206
TI  - Is hepatitis C virus infection associated with thyroid cancer? A case-control
      study.

PMID- 10918207
TI  - Designing a molecular analysis of clonality in tumours.

PMID- 10918208
TI  - Methods for imaging the structure and function of living tissues and cells: 3.
      Confocal microscopy and micro-radiology.
AB  - This review article looks at the development of confocal imaging technology, with
      emphasis on its abilities to overcome some of the problems of imaging life
      processes, particularly in the intact organ or animal. A brief summary of three
      promising micro-imaging modalities is provided (which are microscopical analogues
      of conventional radiological techniques) with a bibliography for the interested
      reader to pursue.

PMID- 10918209
TI  - Immunohistochemical detection of mismatch repair gene proteins as a useful tool
      for the identification of colorectal carcinoma with the mutator phenotype.
AB  - There are two well-defined pathways for colorectal carcinogenesis, the suppressor
      and the mutator pathways. The latter is characteristic of hereditary non
      polyposis colorectal cancer (HNPCC), but can also be found in a subset of
      sporadic colorectal cancer (SCC) possessing distinctive clinical and pathological
      features, namely early age of onset, location in the right colon, poor
      differentiation, and a predominant mucinous component. This mutator pathway
      results from inactivation of mismatch repair (MMR) genes, namely MSH2 and MLH1.
      The aim of this study was to ascertain if abnormal MMR protein gene expression is
      a good indicator for identifying tumours from the mutator pathway. Seventy-six
      cases of SCC were studied by immunohistochemistry using two monoclonal mouse
      antibodies that react against MSH2 and MLH1 protein gene products.
      Immunoexpression was assessed both in tumour and in non-neoplastic, adjacent and
      distant mucosa. Microsatellite instability (MSI) was detected by evaluating the
      length of poly(CA) repeated sequences at seven loci, or by the detection of small
      unstable alleles in a poly(A) repeat - BAT-26. Except for BAT-26, in which only
      tumour DNA was used, MSI analysis was performed in both tumour and normal mucosal
      DNA. MSI was classified as high (MSI-H), low (MSI-L) or stable (MSS). Abnormal
      protein expression was found in 9/76 (12%) tumours. Immunohistochemistry for
      hmlh1 and hmsh2 detected 75% of MSI-H. There was also a highly significant
      correlation between the observed immunoexpression and several clinical and
      pathological characteristics described as the phenotypic profile of the mutator
      pathway, such as right-sided location (p=0.003), mucin production (p=0.008), and
      a peritumoural lymphoid infiltrate (p=0.009). Non-neoplastic adjacent mucosa
      showed normal hMSH2 expression in all cases, but in ten cases there was no hMLH1
      expression in this transitional mucosa, which is known to display an alterated
      mucin pattern and a high proliferative rate. These results demonstrated a good
      correlation between hMLH1 and hMSH2 gene immunoexpression and the clinico
      pathological features characteristic of the mutator phenotype and support the use
      of this method as a rapid and efficient way to detect tumours arising from this
      pathway.

PMID- 10918210
TI  - Effect of mutation and conformation on the function of p53 in colorectal cancer.
AB  - In vitro studies have shown that immunoprecipitation with conformation-specific
      antibodies allows discrimination between different forms of p53; however, the
      significance of this has not been determined for human tumours. This study
      therefore examined p53 conformation in colorectal tumours and correlated this
      with mutational status and evidence of in vivo p53 downstream activity. Moreover,
      it was shown that for in vitro cell lines, DNA-damaging agents induce wild-type
      p53 to form a mutant conformation (PAb240+), with a concomitant rise in p21(WAF
      1) expression. Induction of p53-mediated apoptosis, on the other hand, is
      associated with a wild-type conformation (PAb1620+). These results were confirmed
      for wild-type p53 in colorectal tumours. A range of p53 point mutations were
      found in exons 5-8 in colorectal tumours. Mutants with a wild-type conformation
      gave weak immunohistochemical staining, whereas mutations with flexible
      conformation (240+/1620+) gave intense positivity. Interestingly, this latter
      group of flexible mutants was also associated with features of poor prognosis.
      These studies show that not all p53 mutants are equal; thus, knowledge of the p53
      status of a tumour may be required for a more precise prediction of prognosis and
      response to treatment for cancer patients.

PMID- 10918211
TI  - Apoptosis, proliferation, and angiogenesis in oral tissues. Possible relevance to
      tumour progression.
AB  - Experimental animal models have demonstrated that angiogenesis is essential for
      tumour progression, whilst sustained tumour growth requires a positive balance
      between tumour cell proliferation and cell death (apoptosis). The aim of this
      study was to determine the relative contribution of apoptosis, proliferation, and
      angiogenesis to disease progression in the oral mucosa. Histological sections of
      47 archival specimens were examined; these included four groups of oral tissues:
      normal mucosa (n=12), moderate dysplasia (n=11) severe dysplasia (n=6), and
      squamous cell carcinoma (n=18). Apoptotic cells were visualized by in-situ end
      labelling of DNA, proliferative cells by staining with Ki-67 antibody, and blood
      vessels with von Willebrand factor (vWF) antibody. One-way analysis of variance
      showed that indices of apoptosis (AI), proliferation (PI), and angiogenesis
      (vascularity) increased significantly with disease progression from normal oral
      mucosa, through dysplasia, to carcinoma (p<0.0001 for every index). The increase
      from normal mucosa to moderate dysplasia was significant for PI and vascularity,
      but not for AI. In contrast, the increase from dysplasia to carcinoma was
      significant for AI and vascularity, but not for PI. These data suggest that
      disease progression in the oral mucosa is accompanied by angiogenesis and
      increases in both epithelial proliferation and apoptosis. Net epithelial growth
      results from proliferation starting earlier and proceeding at a higher rate than
      apoptosis.

PMID- 10918212
TI  - Fibrosis in undifferentiated (anaplastic) thyroid carcinomas: evidence for a dual
      action of tumour cells in collagen type I synthesis.
AB  - The mechanisms involved in stromal reactions and fibrosis in solid malignant
      tumours are incompletely understood. In the present study, collagen type I
      production was investigated in tissues and cell lines derived from human
      undifferentiated (anaplastic) thyroid carcinomas, a highly aggressive, often
      fibrotic malignancy with mesenchymal phenotype. In situ hybridization showed the
      expression of pro-alpha1(I) collagen mRNA throughout the stromal part of the
      tumours. However, immunofluorescence staining using an anti-pro-collagen type I
      antibody revealed the synthesis of pro-collagen type I protein mainly in stromal
      cells juxtaposed to nests of tumour cells. In one out of five tissue samples from
      human undifferentiated thyroid carcinomas, pro-alpha1(I) collagen mRNA expression
      was also found in a small number of tumour cells. Several well-characterized cell
      lines established from undifferentiated thyroid carcinomas, two from tumours
      included in the present study, expressed both pro-alpha1(I) collagen and prolyl 4
      hydroxylase mRNA, and three of these cell lines also synthesized native triple
      helical collagen type I. Taken together, these data suggest that stromal
      fibroblasts are the main producers of collagen type I in anaplastic thyroid
      tumours. The carcinoma cells seem to play a regulatory role, stimulating the
      synthesis of collagen type I protein in the surrounding stroma by increasing pro
      alpha1(I) collagen mRNA translation. However, collagen type I production by the
      carcinoma cells might also contribute to the marked desmoplasia commonly seen in
      these tumours.

PMID- 10918213
TI  - Decreased immunoreactivity for cell-cycle regulator p27(Kip1) in Kaposi's sarcoma
      correlates with higher stage and extracutaneous involvement.
AB  - A consistent relationship has been established between the development of
      Kaposi's sarcoma (KS) and human herpes virus-8 (HHV8) infection. HHV8-encoded v
      cyclin, through its complexing with cyclin-dependent kinase 6, contributes to the
      phosphorylation and proteasome-mediated degradation of p27(Kip1). On the other
      hand, down-regulation of p27(Kip1) expression seems to facilitate metastatic
      dissemination in a variety of human neoplasms. Although the neoplastic nature of
      KS remains controversial, it has been repeatedly demonstrated that in some
      patients KS may behave as a malignant neoplasm and follow an ominous course,
      especially in HIV-positive patients and when associated with extracutaneous
      involvement. To determine whether decreased p27(Kip1) levels are also related to
      more aggressive behaviour in KS, it was decided to investigate p27(Kip1)
      immunoreactivity in KS biopsy specimens and its possible changes in relation to
      cutaneous versus extracutaneous involvement and HIV serological status. Forty
      nine cases of KS (29 AIDS-related and 21 classical) corresponding to 30 cutaneous
      biopsy specimens (ten macules, seven plaques, and 13 tumours) and 19
      extracutaneous biopsy specimens were immunostained to determine the expression of
      p27(Kip1) and the proliferation marker Ki-67 antigen. The mean percentages of
      p27(Kip1)-positive cells were significantly higher in biopsy specimens from skin
      lesions (77.8+/-21.1) than in those from extracutaneous locations (42.0+/-26.0).
      Amongst cutaneous lesions, p27(Kip1) expression was significantly higher in
      macules (83.8+/-18.5) and plaques (91.4+/-6.4) than in tumours (65.8+/-22.6). Ki
      67 immunoreactivity showed no correlation with any of the variables studied.
      These results lend support to the hypothesis that decreased levels of p27(Kip1),
      which may have been brought about by HHV8 infection, play a role in KS
      progression through its various histopathological stages, to its eventual
      extracutaneous spread.

PMID- 10918214
TI  - Hodgkin's disease and peripheral T-cell lymphoma: composite lymphoma with
      evidence of Epstein-Barr virus infection.
AB  - This paper reports the case of a patient with a composite lymphoma consisting of
      nodular sclerosing Hodgkin's disease and peripheral T-cell lymphoma. The Hodgkin
      and Reed-Sternberg (HRS) cells harboured the Epstein-Barr virus (EBV) and
      displayed a type II EBV latency (LMP1(+)/EBNA2(-)), whereas the neoplastic T
      cells were EBV-negative. Four years later, the patient presented with a relapse
      of the peripheral T-cell lymphoma. In situ hybridization revealed numerous EBV
      carrying lymphocytes, which were shown to be polyclonal B-cells with a latency
      III pattern of EBV gene expression (LMP1(+)/EBNA2(+)). This observation suggests
      that impairment of EBV-specific immunity in the micro-environment of T-cell
      lymphomas may facilitate the outgrowth of EBV-carrying B-lymphocytes and
      emphasizes the importance of determining the phenotype of EBV-infected cells,
      particularly when studying T-cell lymphomas. The results further suggest that the
      HRS cells and neoplastic T-cells were of different clonal origins. The detection
      of EBV-carrying cell populations admixed with the neoplastic T-cells at primary
      presentation and at relapse raises the possibility that the growth of the T-cell
      lymphoma was dependent on the presence of such cells.

PMID- 10918215
TI  - Epstein-Barr virus is present in neoplastic cytotoxic T cells in extranodal, and
      predominantly in B cells in nodal T non-Hodgkin lymphomas.
AB  - Epstein-Barr virus (EBV)-positive T non-Hodgkin lymphomas (T-NHLs) have been
      described, but it is at present unknown how EBV infects T lymphocytes. It has
      been postulated that cytotoxic T cells (CTLs) or natural killer (NK) cells can be
      infected by EBV during the killing of an EBV-infected target cell. The objective
      of this study was therefore to determine whether the neoplastic cells in EBV
      positive T-NHLs (n=221) of various locations have a cytotoxic phenotype. To
      identify EBV-harbouring cells, combinations were used of EBV-encoded RNA (EBER)
      in situ hybridization (RISH) and immunohistochemistry for T- and B-cell markers
      and the cytotoxic proteins TIA-1 and granzyme B. EBV was detected in the
      neoplastic cells of all nasal T-NHLs (n=9), 5/34 gastrointestinal (GI) T-NHLs,
      and 2/6 lung T-NHLs, but not in primary cutaneous T-NHLs (n=103). Moreover, EBV
      was found in the neoplastic cells of 2/48 nodal anaplastic large cell lymphomas
      (ALCLs), but not in neoplastic T cells of other nodal T-NHLs. However, 5/17 nodal
      peripheral T-NHLs not otherwise specified (PTCLs NOS) and 1/4 T-prolymphocytic
      leukaemias did contain EBV-positive non-T cells. Double staining revealed that in
      EBV-positive extranodal T-NHLs (n=16), the EBER-positive cells had a cytotoxic
      phenotype (TIA-1- and/or granzyme B-positive). In nodal non-ALCL T-NHLs, the EBER
      positive cells were not positive for TIA-1 or granzyme B, nor did they express
      CD3, CD21 or HECA452. Instead, most of these cells expressed the B-cell marker
      CD20. These PTCLs NOS with EBER-positive cells showed features of AILD-like T
      NHL. It is concluded that neoplastic cells of EBV-positive extranodal T-NHLs
      always have a cytotoxic phenotype, supporting the view that EBV can infect CTLs.
      In nodal non-ALCL T-NHL, EBV is only found in T-NHL with AILD-like features and
      is present in B cells, where it may contribute to the outgrowth of a malignant B
      cell clone.

PMID- 10918216
TI  - Melanocytes are not absent in lesional skin of long duration vitiligo.
AB  - This paper provides evidence that melanocytes are still present in the
      depigmented epidermis of patients with vitiligo even after stable disease of 25
      years' duration. Melanocyte cultures were successfully established from
      depigmented epidermal suction blister tissue of all 12 randomly selected patients
      and these cells produced melanin. Even under in vitro conditions, vacuolation of
      melanocytes was demonstrated in five patients with active disease, which was
      reversible upon exogenous addition of bovine catalase to the culture medium. Full
      skin biopsies from 17 patients with vitiligo, obtained from depigmented and
      normally pigmented areas, confirmed the involvement of melanocytes,
      keratinocytes, and Langerhans cells in this disorder. In addition, the presence
      of clustered and single pre-melanosomes in basal and supra-basal keratinocytes of
      lesional and normal epidermis, as well as the retention of single melanocytes in
      lesional epidermis, was demonstrated by light and electron microscopy. Upon
      topical application of a narrow band UVB-activated pseudocatalase, vacuolation,
      granulation, and dilatation of the endoplasmic reticulum completely recovered,
      but the ectopic pre-melanosome shedding remained. Taken together, these
      observations indicate that melanocytes are never completely absent in the
      depigmented epidermis and that these melanocytes can recover their functionality
      in vivo and in vitro upon the removal of hydrogen peroxide. Furthermore, this
      study supports the concept that vitiligo involves the entire epidermal unit in
      both depigmented and 'normal' pigmented skin.

PMID- 10918217
TI  - Apoptosis of macrophages and T cells in tuberculosis associated caseous necrosis.
AB  - Immunity against mycobacteria is almost exclusively confined to epithelioid cell
      granulomas, where a long-lasting but labile balance exists between host and
      bacilli. The relationship between immunity and mycobacteria results in
      regression, growth, or caseation of granulomas. To prove whether caseation is
      associated with apoptosis, biopsy specimens of patients with tuberculosis were
      analysed by electron microscopy and by in situ end-labelling combined with
      immunofluorescence. Apoptotic cells were not detected in regressive granulomas.
      Whereas productive granulomas without histologically recognizable caseous
      necrosis revealed only single apoptotic cells, large numbers of apoptotic CD68+
      macrophages and apoptotic CD3+, CD45RO+ T cells were observed within caseous
      foci. As prime candidates undergoing and/or eliciting apoptosis, vital cells
      surrounding caseous foci were characterized. Immunohistochemistry showed that the
      majority of vital CD68+ macrophages surrounding caseous foci are negative for the
      anti-apoptotic protein bcl2, but positive for the pro-apoptotic protein bax. In
      situ hybridization combined with immunofluorescence demonstrated that the
      majority of the adjacent lymphocytes are activated CD3+, CD45RO+ cells expressing
      the pro-inflammatory cytokine interferon gamma (IFN gamma) and the death ligand
      FasL. These results suggest that caseation is strongly associated with apoptosis
      of macrophages and T lymphocytes; that the onset of apoptosis in macrophages may
      be promoted by the lack of bcl2 and the abundance of bax; and that activation
      induced cell death (AICD) may be responsible for the apoptosis of T cells.

PMID- 10918218
TI  - Expression of vascular endothelial growth factor isoforms and their receptors Flt
      1, KDR, and neuropilin-1 in synovial tissues of rheumatoid arthritis.
AB  - Angiogenesis is an indispensable process in the chronic proliferative synovitis
      and pannus formation of rheumatoid arthritis (RA). This study examined the
      expression of vascular endothelial growth factor (VEGF) isoforms and VEGF
      receptors, Flt-1, KDR and neuropilin-1, in RA and osteoarthritis (OA) synovia,
      and studied the relationship between their expression and the synovial
      angiogenesis. By RT-PCR analysis, the isoform VEGF(121) was constitutively
      expressed in all the RA (17/17 patients) and OA (8/8 patients) synovia. In
      contrast, the expression of the isoform VEGF(165) was observed in 41% of the RA
      synovia (7/17 patients), but was undetectable in the OA samples (0/8 patients).
      The receptor Flt-1 was almost constitutively expressed in RA (15/17 patients) and
      OA (8/8 patients) synovia, while the expression of KDR was detected in the
      synovia of six RA patients (6/17 patients; 35%) but none of the OA patients (0/8
      patients). The expression of neuropilin-1, an isoform-specific receptor for
      VEGF(165) which enhances the binding of VEGF(165) to KDR, was also up-regulated
      in the same RA synovia that expressed KDR. Furthermore, there was a close
      correlation between the expression of isoform VEGF(165) and that of its receptors
      KDR and neuropilin-1. Morphometric analysis demonstrated that the vascular
      density is significantly higher in the RA synovial tissues with expression of
      VEGF(165), KDR, and neuropilin-1 than in those without their expression (p<0.01).
      In situ hybridization and immunohistochemical studies indicated that the cells
      expressing VEGF are macrophage-like synovial lining cells and spindle-shaped
      cells in the sublining cell layer. These results suggest that the selective up
      regulation of the isoform VEGF(165) and its signalling via KDR and neuropilin-1
      play an important role in the synovial angiogenesis which occurs in RA.

PMID- 10918219
TI  - Expression of nitric oxide synthase isoforms and arginase in normal human skin
      and chronic venous leg ulcers.
AB  - Chronic venous ulcers, an example of abnormal wound healing, show chronic
      inflammation with defective matrix deposition which together with the underlying
      vascular pathology, result in delayed healing. L-arginine is known to be
      metabolized by one of two pathways: nitric oxide synthase (NOS), producing nitric
      oxide (NO), or arginase, producing ornithine. NO is involved in many pathological
      conditions including vascular and inflammatory disorders. This study therefore
      investigated the distribution, level and activity of NOS and arginase in chronic
      venous ulcers in comparison with normal skin, using immunocytochemistry, western
      blotting, and enzyme assays. The results demonstrated an increased distribution
      of both NOS and arginase in chronic venous ulcer tissue compared with normal
      skin, with inflammatory cells and vascular endothelial cells as the main sources.
      These data were confirmed by western blot analysis, which showed increased levels
      of both enzymes in chronic venous ulcers. Moreover, there was significantly
      increased activity of both total NOS (p<0.04) and inducible NOS (p<0.05) in
      chronic venous ulcer tissue compared with normal skin, and significantly
      increased activity of arginase (p<0.01) in chronic venous ulcer tissue in
      comparison with normal skin. NO is known to combine with hydroxyl free radicals
      forming peroxynitrite, a potent free radical which causes tissue destruction. NO
      overexpression in chronic venous ulcers may be involved directly or indirectly
      (through production of peroxynitrite) in the pathogenesis and delayed healing of
      chronic venous ulcers, through its effects on vasculature, inflammation, and
      collagen deposition. Arginase is known to enhance matrix deposition. Thus,
      increased levels of arginase in chronic venous ulcers could contribute to the
      pathogenesis of lipodermatosclerosis associated with chronic venous
      insufficiency, predisposing to the formation of chronic venous ulcers and also to
      matrix cuff formation around blood vessels.

PMID- 10918220
TI  - The role of mast cells in ischaemia-reperfusion injury in murine skeletal muscle.
AB  - To determine the role of mast cells in ischaemia-reperfusion (IR) injury to
      skeletal muscle, W(f)/W(f) mast cell-deficient and their corresponding wild-type
      mice were subjected to 70 min tourniquet ischaemia and 24 h reperfusion. As
      measured by nitroblue tetrazolium (NBT) staining, muscle viability was 9% in wild
      type and 94% in mast cell-deficient animals (p<0.001). Assay of residual lactate
      dehydrogenase activity within the injured muscle (p<0.05) and histological
      examination confirmed the greater muscle necrosis in treated wild-type than in
      treated mast cell-deficient mice. There was no significant difference in the
      degree of neutrophil infiltration, tissue myeloperoxidase content or water
      content of IR-injured muscle in the two mouse phenotypes. To determine further
      the role of mast cells in IR injury, wild-type mice were treated 30 min prior to
      reperfusion with an intraperitoneal dose of either saline or the mast cell
      stabilizing agent lodoxamide trometamol (2.5, 7.5, 25 or 75 mg/kg). Twenty-four
      hours after removal of the tourniquet, saline-treated gastrocnemius muscle had a
      mean viability of 14% compared with 28% (p<0.05) and 48% (p<0.01) after 25 mg/kg
      and 75 mg/kg of lodoxamide treatment, respectively. The ability of lodoxamide to
      stabilize mast cells was confirmed by histological examination. Ischaemic muscle
      reperfused for 1 h showed much less degranulation of mast cells in mice
      pretreated with lodoxamide (50 mg/kg) than in saline-treated controls. These
      findings suggest that mast cells are a major source of mediators of necrosis in
      IR injury to skeletal muscle.

PMID- 10918221
TI  - Oestrogen receptor alpha in female fetal, infant, and child mammary tissue.
AB  - Oestrogen receptor alpha (ER alpha) expression was studied in female mammary
      tissue from a series of 35 samples obtained post-mortem, ranging from fetuses of
      13 weeks' gestation to prepubertal children of 12 years. Immunocytochemistry was
      performed on formalin-fixed tissue after microwave antigen retrieval. ER alpha
      was present in epithelial cell nuclei from the 30th week of gestation onwards and
      was markedly up-regulated shortly after birth. For up to 3 months thereafter,
      progesterone receptor was also expressed, indicative that the ER alpha was
      functional. During this period, ER alpha was also present in epithelial cell
      cytoplasm. From this perspective of the developing breast, it is suggested that
      an early postnatal component should be added to the prenatal oestrogen
      hypothesis; further, the significance of ER alpha cytoplasmic staining in the
      adult breast also merits review.

PMID- 10918222
TI  - Double immunofluorescence labelling of routinely processed paraffin sections.
AB  - Double immunoenzymatic labelling of routinely processed human tissues has been
      used in many histopathology laboratories to compare the expression patterns of
      pairs of antigenic markers. However, these techniques are time-consuming, prone
      to background staining, and rarely suitable for detecting two antigens present at
      the same site, since one label tends to obscure the other. This paper reports the
      use of immmunofluorescence for double labelling of pairs of molecular markers in
      routinely processed tissue. The primary antibodies are either monoclonal reagents
      of differing isotype/subclass, or antibodies from different species, and
      labelling is visualized on a conventional fluorescence microscope equipped with a
      cooled CCD camera. Images can be captured and adjusted using personal computer
      hardware and software. This approach could be used for a wide range of tissue
      markers and only minimal tissue autofluorescence was observed. The procedure is
      more rapid than enzyme-based techniques and avoids the problems of interpreting
      two antigens present at the same site. Its establishment involves relatively
      minor expenditure and it may represent the optimal technical approach to the co
      localization of pairs of antigens in routinely processed tissue samples.

PMID- 10918223
TI  - Medical student appraisal of interactive computer-assisted learning programs
      embedded in a general pathology course.
AB  - Computer-assisted learning programs (CALs) were embedded in a course on general
      pathology for medical students at the University of Edinburgh Medical School.
      Students' reactions to the programs were evaluated. Students completed written
      questionnaires and were interviewed and observed as they used the CALs. Students
      liked the CALs and felt that they were integrated with other parts of their
      teaching and aided them in understanding the subject material. Different question
      styles were variably appreciated. The most useful aspects of the CALs were the
      interactive parts (questions and answers), summaries, pictures, learning at the
      individual's own pace, and question practice, especially with MCQs. Students
      found the CALs an effective learning tool, particularly when linked with other
      course components as a complement to, rather than a replacement for, other
      learning methods.

PMID- 10918224
TI  - E-cadherin mutations in gastric carcinoma.

PMID- 10918225
TI  - Author's reply

PMID- 10918226
TI  - CD95 ligand expression as a criterion of malignant transformation in breast
      cancer.

PMID- 10918228
TI  - COMMENTARY.

PMID- 10918227
TI  - Author's reply

PMID- 10918229
TI  - Changes in body mass index and prevalence of overweight in survivors of childhood
      acute lymphoblastic leukemia: role of cranial irradiation.
AB  - BACKGROUND: The risk factors responsible for an increased prevalence of obesity
      or overweight in survivors of acute lymphoblastic leukemia (ALL) remain
      controversial. We evaluated changes in body mass index (BMI) in a cohort of ALL
      survivors, all of whom have been followed until completion of linear growth.
      PROCEDURE: BMI (weight/height(2)) was used as an index of adiposity and was
      calculated at diagnosis, at the end of treatment, and at attainment of final
      height in a cohort of 126 (59 males) survivors of ALL. BMI was adjusted for age
      and sex by computing a BMI standard deviation score (SDS) or z score. The
      spectrum of therapies used included intrathecal chemotherapy given alone (n = 38)
      or combined with cranial irradiation (CRT; 18 Gy, n = 35; 24 Gy, n = 53) and
      exposure to prednisone at a low dose (<3.5 gm, n = 49), medium dose (3.5-9.4 gm,
      n = 46), or high dose (>9.4 gm, n = 30). RESULTS: Overall, mean +/- SEM BMI-SDS
      increased significantly between diagnosis (-0.18 +/- 0.08) and the end of therapy
      (0.41 +/- 0.09, P < 0.01), with no significant change thereafter. For patients
      without CRT, mean BMI-SDS remained unchanged, whereas, for those so treated, mean
      BMI-SDS increased significantly between diagnosis and the completion of therapy
      (P < 0.001). The change in mean BMI-SDS was greater in the 24 Gy group vs. the 18
      Gy CRT sample (P < 0.005). In a multivariate logistic regression model, CRT was
      an independent predictor of being overweight (BMI >/=85 percentile) at attainment
      of final height [odds ratio = 1.6 (95% confidence interval 1.0-23. 1)]. The
      percentage of subjects who were overweight at attainment of final height was
      10.5%, 40%, and 38% for subjects treated with no CRT, 18 Gy CRT, or 24 Gy CRT,
      respectively (P < 0.01). CONCLUSIONS: Children with ALL given CRT develop
      increases in their BMI-SDS early on and during treatment and remain at
      significant risk for becoming overweight as young adults, a development that may
      increase their already heightened risk for various adverse health outcomes.

PMID- 10918230
TI  - P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma
      tumors and cell lines.
AB  - BACKGROUND: The p53 tumor suppressor gene is the most commonly mutated gene in
      human cancer, and mutations arise in a wide variety of tumor types. Wild-type p53
      functions as a regulator of apoptosis, so mutations in the p53 gene are generally
      associated with aggressive tumors and a poor prognosis. PROCEDURE: We have
      investigated the p53 mutation and MDM2 amplification frequencies in biopsies from
      pediatric rhabdomyosarcoma (RMS) tumors and cell lines by SSCP and Southern
      analyses. RESULTS: A mutation was detected in only 1 of 20 tumor specimens (5%),
      whereas the frequency in established RMS cell lines was significantly higher
      (6/10, 60%). p53 Mutations were more common in cell lines derived from tumors
      previously exposed to chemotherapy compared to those derived from tumors at di
      agnosis, and it is likely that these mutations enhanced the probability of
      successful long-term culture. The frequency of MDM2 gene amplification in patient
      biopsies was also low (2/20, 10%). Interestingly, complete responses to treatment
      were obtained in the two patients with tumors that demonstrated amplification of
      MDM2. The response to treatment of patients with tumors wild-type for p53 and
      without MDM2 amplification was quite varied, indicating that expression of a wild
      type p53 gene at diagnosis cannot always facilitate a favorable outcome.
      CONCLUSIONS: p53 mutation and MDM2 gene amplification frequencies are extremely
      low in RMS tumors, but a wild-type p53 genotype is not always associated with a
      favorable prognosis.

PMID- 10918231
TI  - Issues in the local control of rhabdomyosarcoma.
AB  - BACKGROUND: Rhabdomyosarcoma (RMS) is a heterogeneous disease consisting of
      several different histologies arising from a variety of anatomic sites.
      Approximately half of the children who die of this tumor have failure at the
      primary site of involvement, making local control an important component of
      therapy. PROCEDURE: Published literature and newly analyzed data from the
      Intergroup Rhabdomyosarcoma Study Group (IRSG) regarding local control of RMS
      were reviewed. Information regarding the role of various local control modalities
      for different primary disease sites is presented along with new directions for
      clinical research. RESULTS: Local control rates for RMS average 80% for group III
      tumors, with large variations seen for different anatomic sites. Important gains
      in functional outcome for certain sites such as gynecologic system and
      bladder/prostate have been achieved by optimizing the use of the various
      treatment modalities. Local control at other sites such as the chest and
      extremities remains a problem. CONCLUSIONS: Advances in surgical and radiotherapy
      techniques coupled with multiagent chemotherapy are providing improved local
      control with decreasing morbidity. Optimal outcome is dependent on close
      collaboration between surgical, radiotherapy, and pediatric oncology specialists.

PMID- 10918232
TI  - Spontaneous remission of congenital acute nonlymphoblastic leukemia with normal
      karyotype in twins.
AB  - BACKGROUND: Congenital acute nonlymphoblastic leukemia (cANLL) is an extremely
      rare event and represents only 0.5-1% of the leukemias in the first year of life.
      It is usually more common among patients with chromosomal abnormalities.
      Transient myeloproliferative disease (TMD) is an hyperleukocytosis entity that
      occurs almost exclusively in Down syndrome patients and remits spontaneously.
      Spontaneous remission of congenital leukemia has been reported and related to the
      presence of an extra chromosome 21. PROCEDURE: A pair of non-Down syndrome
      newborn twins presented with a clinical picture of skin rash and
      hyperleukocytosis. Twin B had full-blown cANLL with bone marrow, peripheral
      blood, skin, CSF, and placental invasion. Twin A presented transient peripheral
      blood and skin involvement by the same type of blast cells. No cytotoxic therapy
      was given. With 2 years follow-up, they continue to do well. RESULTS: Histologic
      and immunophenotypical analysis of placentas, cord blood, skin, CSF, bone
      marrows, and peripheral blood revealed a consistent picture of intrautero cANLL
      in twin B, with transplacental invasion of twin A. Normal and blast cells were
      found to be karyotypically normal. Spontaneous remission occurred. CONCLUSIONS:
      cANLL with karyotypically normal blasts can develop a self-limited clinical
      course, which has resemblances to TMD.

PMID- 10918233
TI  - Sperm and ova conservation: existing standards of practice in North America.
AB  - BACKGROUND AND PROCEDURE: Rapid advances have occurred in both reproductive
      medicine and survival from childhood cancer. To establish the current level of
      best clinical practice for sperm, ovarian, and prepubertal tissue collection and
      storage, a cross-sectional survey of a major pediatric oncology collaborative
      study group (Pediatric Oncology Group, POG) was performed. RESULTS: Of the 110
      centers surveyed, 69 questionnaires (63%) were completed. No responding center
      had guidelines regarding which young people should be offered sperm, ovarian, or
      prepubertal testicular tissue conservation; 93% centers had offered sperm and 10%
      ova conservation; 15% had offered sperm conservation to males prior to completion
      of sexual development and 3% to girls prior to sexual maturation. All centers
      were more likely to offer sperm conservation than ova conservation for any given
      disease. The most common diseases for which conservation was offered were Hodgkin
      and non-Hodgkin lymphoma, and sarcomas. Fertility counseling was offered in a
      variety of settings by 71% of centers by health care professionals, including
      doctors, nurses, social workers, psychologists, and geneticists. CONCLUSION:
      There was little agreement regarding appropriate indications for, and method of,
      gamete preservation in children's cancer centers. It is hard to establish best
      clinical practice from these data. Unresolved medical, legal, and ethical issues
      necessitate the development of a voluntary code of practice and guidelines in
      order to ensure good clinical practice.

PMID- 10918234
TI  - Clinical trials in children with cancer--the problem of early randomisation.

PMID- 10918235
TI  - Guidelines for the recognition, prevention, and remediation of burnout in health
      care professionals participating in the care of children with cancer: report of
      the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology.
AB  - This is the eighth official document of the SIOP Working Committee on
      Psychosocial Issues in Pediatric Oncology, instituted in 1991. It deals with a
      topic discussed and approved by the SIOP Committee; namely, "Recognition,
      prevention, and remediation of burnout in health care professionals participating
      in the care of children with cancer." It is addressed to the Pediatric Oncology
      community and outlines: 1) the general definition of burnout as mental and
      physical exhaustion, indifference, sense of failure as a professional, and sense
      of failure as a person; 2) the causes of burnout from the nature of the work
      itself, the work environment, and the characteristics of the individual; 3) the
      prevention of burnout, changing the detrimental aspects of one's work environment
      and modifying one's own behavior; and accepting methods to remediate burnout when
      it occurs.

PMID- 10918236
TI  - Recent advances in the genetics of childhood renal cancers: a report of the 3rd
      International Conference on the molecular and clinical genetics of childhood
      renal tumors, together with the Mitchell Ross symposium on anaplastic and other
      high risk embryonal tumors of childhood, 8-10th April 1999, Wistar Institute,
      Philadelphia, PA.

PMID- 10918238
TI  - T-cell lymphoma in a child with multicentric Castleman disease.

PMID- 10918237
TI  - Allergic reaction to high-dose methotrexate.

PMID- 10918239
TI  - Tumors in the sternal region of young children.

PMID- 10918241
TI  - Immature teratoma arising from an intra-abdominal testis in a 5-month-old boy.

PMID- 10918240
TI  - ETV6-NTRK3 gene fusion in metastasizing congenital fibrosarcoma.

PMID- 10918242
TI  - Primary orbital melanoma in a child.

PMID- 10918243
TI  - Ovarian sex cord tumor with annular tubules associated with precocious puberty.

PMID- 10918244
TI  - Nonrhabdomyosarcomatous botyroid tumour of the cervix uteri: is it a new entity?

PMID- 10918245
TI  - Neuroblastoma in an infant revealing middle aortic syndrome.

PMID- 10918246
TI  - False-negative metaiodobenzylguanidine scintigraphy at diagnosis of
      neuroblastoma.

PMID- 10918247
TI  - Auditory function is unaffected by treatment with ifosfamide in children and
      adolescents.

PMID- 10918248
TI  - Predawn.

PMID- 10918250
TI  - Complex phenotypes in metabolic muscle diseases.

PMID- 10918251
TI  - Surgical treatment of common entrapment neuropathies in the upper limbs.
AB  - Entrapment neuropathies of the upper extremity are common, debilitating
      conditions. Most patients with these neuropathies are readily diagnosed on purely
      clinical grounds and may be effectively managed with nonoperative measures.
      However, the broad differential diagnosis often necessitates electrodiagnostic
      testing and radiographic imaging to clarify the situation. This review focuses on
      three of the most common entrapment neuropathies in the upper limbs: carpal
      tunnel syndrome (median nerve entrapment at the wrist), cubital tunnel syndrome
      (ulnar nerve entrapment at the elbow), and radial tunnel syndrome (posterior
      interosseous nerve entrapment). Anatomical considerations, patient evaluation,
      indications for surgical intervention, options for surgical approaches, outcomes,
      and complications are discussed.

PMID- 10918252
TI  - Molecular analysis of Spanish patients with AMP deaminase deficiency.
AB  - We found six patients with AMPD deficiency in muscle who were homozygous for the
      most common mutation, Q12X in the AMPD gene (AMPD1), associated with this
      disease. Three patients had AMPD deficiency alone, showing a mild clinical
      phenotype. Two patients showed a defect of PPL in muscle, and were homozygous for
      the most common mutation associated with McArdle's disease, R49X in the muscle
      PPL gene (PYGM). In one of these patients, the clinical phenotype was more severe
      than usually seen in patients with McArdle's disease. The remaining patient
      harbored the mtDNA A3243G mutation, showing one of the usual clinical patterns
      associated with this mutation. We conclude that the Q12X mutation in AMPD1 may
      result in a mild clinical effect; that it is frequent in the Spanish population,
      and therefore frequently associated with other metabolic diseases; and that the
      effect of the association of AMPD and PPL deficiencies seems to be neutral.

PMID- 10918253
TI  - Cutaneous silent periods in patients with Fabry disease.
AB  - We assessed the cutaneous silent period (CSP) in 24 patients with Fabry disease
      with small-fiber sensory neuropathy and 12 normal subjects to test the hypothesis
      that small-diameter afferents are responsible for producing the CSP. Sensory
      nerve conduction studies and quantitative sensory testing for cold and vibration
      detection thresholds were also measured. Overall, Fabry patients had impaired
      thermal, but not vibration, detection thresholds, with greatest impairment in the
      feet. In the upper extremity, CSP latencies, duration, and suppression of
      electromyographic activity (EMG) did not differ. In the lower extremity, patients
      had reduced suppression of EMG during the CSP compared to normal controls. CSP
      durations exhibited a bimodal distribution in patients, including a subset of
      seven patients with durations shorter than all controls. This subset had profound
      loss of thermal sensation in the feet, but this was also true of some patients
      who had normal CSPs. Patients with shortened CSPs had modestly elevated vibration
      thresholds and reduced sensory potentials in comparison to patients with normal
      CSPs. Reduced CSPs in Fabry patients are associated with, but not entirely
      explained by, the severity of small-fiber neuropathy as measured by quantitative
      sensory testing. The possibility that large-diameter fibers provide a minor
      contribution to producing the CSP should be considered.

PMID- 10918254
TI  - Influence of oxygen supply on activation of group IV muscle afferents after low
      frequency muscle stimulation.
AB  - Anaerobic muscle metabolism and local release of inflammatory mediators play key
      roles in the mechanism of postfatigue-induced activation of group IV muscle
      afferents. The present study focused on activation of these muscle afferents
      after a 3-min period of low-frequency muscle stimulation (LFMS) in different
      conditions of muscle oxygenation, such as occur in patients with respiratory
      insufficiency and subjects living at high altitude. In anesthetized rabbits,
      spontaneous activity of group IV afferents (conduction velocity = 1.52 +/- 0.13
      m.s(-1)) from the tibialis anterior muscle was recorded at rest (baseline) and
      then after LFMS under normoxic (PaO(2) = 113 mmHg), hyperoxic (PaO(2) = 186
      mmHg), or hypoxic (PaO(2) = 35 mmHg) conditions. The maximal force decay at the
      end of LFMS did not differ significantly with respect to conditions of muscle
      oxygenation. Compared with normoxia, hypoxia significantly increased the baseline
      activity of group IV muscle afferents, whereas no effect was noted when hypoxia
      followed a period of hyperoxia. LFMS-induced activation of group IV afferents
      occurred in all circumstances, except when hypoxia was first tested. The
      activation of group IV muscle afferents after LFMS was markedly reduced when
      hypoxia followed normoxia (+14% versus +27%) or hyperoxia (+55% versus +144%),
      whereas it was accentuated when hyperoxia followed hypoxia (+25% versus +8%). We
      concluded that the sensorimotor control of skeletal muscles may be altered during
      acute hypoxia but facilitated after reoxygenation.

PMID- 10918255
TI  - Dipolar source modeling of somatosensory evoked potentials to painful and
      nonpainful median nerve stimulation.
AB  - Dipolar source modeling might help in clarifying whether somatosensory evoked
      potentials (SEPs) after electrical stimulation at painful intensity contain any
      information related to the nociceptive processing. SEPs were recorded after left
      median nerve stimulation at three different intensities: intense but nonpainful
      (intensity 2); slightly painful (pain threshold; intensity 4); and moderately
      painful (intensity 6). Scalp SEPs at intensities 2, 4, and 6 were fitted by a
      five-dipole model. When the strength modifications of the source activities up to
      40 ms were examined across the different stimulus intensities, no significant
      difference was found. In the later epoch (40-200 ms), a posterior parietal dipole
      and two bilateral sources probably located in the second somatosensory (SII)
      areas increased significantly their dipole moments when the stimulus was
      increased from 2 to 4 and became painful. Since no difference was found when the
      stimulus intensity was increased from 4 to 6, the observed increase of the
      dipolar strengths is probably related to a variation of the stimulus quality
      (nonpainful vs. painful), rather than of the stimulus intensity per se. Our
      findings lead us to conclude that a large convergence of nociceptive and non
      nociceptive afferents probably occurs bilaterally in the SII areas.

PMID- 10918257
TI  - Autonomic dysfunction in idiopathic carpal tunnel syndrome.
AB  - While the sensorimotor features of carpal tunnel syndrome (CTS) are well known, a
      prospective, systematic study of autonomic disturbances in CTS is lacking. Of 139
      limbs with CTS (76 patients), autonomic symptoms were reported in 76 (47
      patients). Of these, 59% consisted of swelling of the fingers, 39% dry palms, 33%
      Raynaud's phenomenon, and 32% blanching of the hand. Sympathetic skin response
      (SSR) had a sensitivity/specificity ratio of 34/89% in CTS with autonomic
      symptoms. The presence of autonomic disturbances was significantly associated
      with female gender (odds ratio 4.06, 95% CI 1.5-11.4, P = 0.007), SSR
      abnormalities (odds ratio 4.3, 95% CI 1. 6-11.4, P = 0.003), and severity of
      electromyographic findings (odds ratio 1.8, 95% CI 1-3.3, P = 0.04) but not age,
      duration of disease, or clinical severity in a binary logistic regression model.
      Autonomic disturbances are common (55%) in CTS, occurring with increasing
      severity of electrophysiologic findings.

PMID- 10918256
TI  - Gabapentin may be hazardous in myasthenia gravis.
AB  - A patient with painful neuropathy developed ocular, facial, and masticatory
      weakness and fatigue after 3 months of gabapentin (GBP) treatment (400 mg/day).
      An elevated level of serum acetylcholine receptor antibodies (AChR-Ab) was
      detected. The patient recovered following pyridostigmine therapy and withdrawal
      of GBP and, 2 years later, is practically asymptomatic despite positive AChR-Ab.
      Because of this clinical observation, we gave 150 mg/kg GBP to rats with
      experimental autoimmune myasthenia gravis (EAMG). Repetitive nerve stimulation at
      3-Hz was performed, and the 5th/1st amplitude ratio was used to calculate the
      decremental response. In all EAMG rats, GBP induced a transient, abnormal
      decrement (7-20%) 90 to 240 min after administration. No decrement was induced by
      GBP in normal rats. Thus, GBP aggravates the decrement in EAMG. The mechanism
      involved in the hitherto unreported possible unmasking of myasthenia gravis (MG)
      by GBP is unknown. Gabapentin should be used with caution in this disease.

PMID- 10918258
TI  - Neuropeptide- and tyrosine hydroxylase-immunoreactive nerve fibers in painful
      Morton's neuromas.
AB  - We examined the expression of three neuropeptides that have been implicated in
      nociceptive transmission, and the sympathetic nerve fiber marker tyrosine
      hydroxylase, in 11 painful human Morton's neuromas, using immunohistochemistry.
      Antibodies against the neural markers RT97 and PGP 9.5 were used to map the
      general nerve fiber organization of the neuromas. Four specimens of normal human
      peripheral nerves were used as controls. Substance P, calcitonin gene-related
      peptide, and neuropeptide Y immunoreactivities were more pronounced in neuroma
      tissue than in control nerves. Neuropeptide immunofluorescence was seen both in
      larger nerve fiber trunks and in masses of disorganized axon profiles dispersed
      in loose connective tissue. Tyrosine hydroxylase immunoreactivity was present at
      varying levels of expression in neuroma nerve fiber trunks, in connective tissue
      nerve fiber bundles, and around some blood vessels. Our findings suggest that
      neuropeptides are involved in the response to injury in Morton's neuromas and
      that they could play a role in initiation or modulation of pain. In addition,
      pain from Morton's neuromas could be influenced by sympathetic nerve fibers.

PMID- 10918259
TI  - Inhibition of motor unit firing during experimental muscle pain in humans.
AB  - Electromyographic activity was recorded in the masseter muscle to investigate
      whether the firing characteristics of single motor units (SMUs) were affected by
      muscle pain. Capsaicin was injected into the masseter to induce pain. The
      interspike interval (ISI) and recruitment threshold of SMUs were measured while
      subjects performed isometric contractions at 5, 7.5, 10, 15, and 20% of maximum
      voluntary contraction. All subjects were able to maintain a stable isometric
      force during pain, but the mean ISI was significantly increased without changing
      the recruitment threshold. In all the experimental conditions, the firing
      frequency increased with increasing force, and SMUs recruited at low force fired
      at higher rates for all force levels. These results suggest that acute
      stimulation of nociceptive muscle afferents inhibits SMU activity without
      changing recruitment order in the homonymous muscle.

PMID- 10918261
TI  - Hybrid fibrillation potentials and positive sharp waves.
AB  - Fibrillation potential configurations are characterized as initially positive
      triphasic waveforms, whereas positive sharp waves appear biphasic with an initial
      positive deflection. Careful observation of single muscle fiber discharges in
      denervated muscle, however, can reveal many different-appearing and stable firing
      waveforms that resemble a bifid positive sharp wave or some form of combined
      fibrillation potential and positive sharp wave. In this investigation, a number
      of atypical-appearing single muscle fiber discharges are hypothesized to arise
      from particular interactions between the muscle fiber and recording electrode.
      Single muscle fiber potentials are modeled as originating from a single
      denervated muscle fiber's former endplate and midfiber region as well as from the
      fiber's tendinous termination for both a compressed and sealed end effect. The
      modeled waveforms' appearance corresponds well to those obtained clinically and
      the necessary interpotential summated templates' temporal domains are feasible
      for action potential termination at the electrode with subsequent reinitiation
      beyond the proposed peri-electrode compressed region. It is hypothesized that the
      majority of hybrid waveforms are the result of a single muscle fiber action
      potential terminating at a recording electrode while also initiating a "skipped"
      activation of the muscle fiber past the electrode resulting in the summation of
      two distinct time-locked waveforms.

PMID- 10918260
TI  - Cryopreservation of peripheral nerve grafts.
AB  - The utilization of viable biological nerve graft substitutes and nerve allografts
      raises the problem of nerve storage. To clarify this, rat sciatic nerve segments
      were harvested and stored in Dulbecco's modified eagle medium. The segments were
      divided into three groups. In the first group, no cryoprotectant was added,
      whereas the second had 10% dimethyl sulfoxide (DMSO) added as cryoprotectant.
      These two groups of nerve segments were subjected to controlled freezing. In a
      third group, segments were frozen uncontrolled in liquid nitrogen (-196 degrees
      C). All nerves were replanted orthotopically. Fresh conventional autografts
      (fourth group) served as control group. Histologically, freezing did not affect
      the structural elements such as basal lamina tubes and perineurial tissue.
      Morphometrically, all cryopreserved grafts had significantly reduced axon counts
      and less myelinization than did controls. Cryoprotected nerves (group 2) showed
      no different morphometric parameters compared with the group without DMSO (group
      1). Controlled freezing was superior to uncontrolled freezing (group 3). Impaired
      regeneration was attributed mainly to delayed Wallerian degeneration and slower
      revascularization. Moreover, decreased survival of resident Schwann cells in the
      graft may impair regeneration due to the lack of neurotrophic, neurotropic, and
      attachment factors in early regeneration. Grafts subjected to controlled freezing
      support axonal regeneration to a certain extent, but further studies are required
      to assess various cooling patterns, cryoprotectants, and graft revascularization.

PMID- 10918262
TI  - Clinical predominance of proximal upper limb weakness in CMT1A syndrome.
AB  - We report an Austrian family with proximal muscle weakness and wasting
      predominantly of the shoulder girdle musculature, normal or slightly reduced
      distal muscle power, mild foot deformity, absent or reduced tendon reflexes in
      the lower limbs, and normal or slightly diminished sensation.
      Electrophysiologically, motor nerve conduction velocities were slowed to less
      than 33 m/s, distal latencies were prolonged, and compound motor action
      potentials were low. Sensory nerve conduction velocities were extremely reduced
      or no sensory potentials were recordable. Genetic testing in three affected
      individuals revealed a duplication of the chromosomal region 17p11.2. In
      addition, genetic testing for facioscapulohumeral muscular dystrophy (FSHD)
      revealed a 33 kb EcoRI fragment on chromosome 4q35 in one affected individual and
      in the clinically normal parent, whereas in a second affected person normal DNA
      sizes were observed. These clinical findings define a new phenotypic variant
      associated with the Charcot-Marie-Tooth 1A duplication. This may be due to a
      mutation in another gene contained in the 1.5 Mb duplication although mutations
      in the peripheral myelin protein 22 gene have been excluded. Alternatively, the
      genetic background of other genes in the family may modify the phenotypic
      expression, as found in other inherited diseases. The unusual phenotype cannot be
      explained by the concomitant presence of FSHD despite some evidence for
      coexistance in one individual.

PMID- 10918263
TI  - Quantitative electromyography of the external anal sphincter in Parkinson's
      disease and multiple system atrophy.
AB  - The distinction of multiple system atrophy (MSA) from Parkinson's disease (PD)
      can be difficult, especially early in the disease. In MSA degeneration of sacral
      anterior horn cells (Onuf's nucleus) results in denervation-reinnervation of anal
      and urethral sphincter muscles, which can be recognized as neurogenic
      electromyographic (EMG) changes of motor unit potentials. Sphincter EMG has
      therefore been recommended as a test for distinguishing MSA from PD. Our results
      confirm the presence of marked neurogenic EMG changes of the external anal
      sphincter muscle in patients with probable MSA compared to healthy controls.
      However, in patients with probable PD, our quantitative EMG data show a scatter
      from normal to marked neurogenic changes and the degree of EMG abnormality is
      correlated to the duration of the disease. Thus an abnormal sphincter EMG cannot
      be taken as a strong indicator of MSA rather than PD in the individual patient,
      especially in long-standing cases.

PMID- 10918264
TI  - Dose-dependent effects of inspiratory muscle training in neuromuscular disorders.
AB  - The goal of this study was to show whether a correlation exists between the
      intensity of specific respiratory muscle training and the improvement of strength
      and endurance in inspiratory musculature in patients with neuromuscular disorders
      (NMD). Sixteen patients with NMD (13 with Duchenne muscular dystrophy and 3 with
      spinal muscular atrophy) performed inspiratory muscle training (IMT) at home with
      a special training apparatus for 9 months. Maximal inspiratory mouth pressure
      (PI(MAX)) and 12s-maximum voluntary ventilation (12s-MVV) test served as
      parameters for inspiratory muscle strength and endurance, respectively. In
      patients whose inspiratory vital capacity (VC(in)) declined by less than 10%
      during the year before training began (n = 10), a significant positive
      correlation was found between the number of successfully completed strength and
      endurance exercises and the improvement of PI(MAX) (P < 0.05) and 12s-MVV (P <
      0.05). In patients whose VC(in)-decline exceeded 10% (n = 6), indicating more
      progressive respiratory system involvement of the disease, no significant
      correlation between the improvement of PI(MAX) and 12s-MVV and the intensity of
      training was found. In patients with NMD, the effects of IMT-runs are dose
      dependent, provided that the respiratory system involvement of the disease is
      only slowly progressive.

PMID- 10918265
TI  - Test-retest reliability of combined sensory index: implications for diagnosing
      carpal tunnel syndrome.
AB  - When compared to single nerve conduction tests, the combined sensory index (CSI)
      has been shown previously to have superior sensitivity and specificity for
      diagnosing carpal tunnel syndrome. The CSI is the sum of (1) median-ulnar ring
      finger antidromic latency difference at 14 cm (ring-diff); (2) median-radial
      thumb antidromic latency difference at 10 cm (thumb-diff); and (3) median-ulnar
      midpalmar orthodromic latency difference at 8 cm (palm-diff). To evaluate the
      reliability of single nerve conduction tests (ring-diff, thumb-diff, and palm
      diff) vs. a combined summary variable (CSI), we conducted a prospective study
      during which the same investigator performed test and retest sessions on one hand
      of 32 subjects. Results showed that the CSI had the highest test-retest
      reliability (Spearman rho = 0.95), when compared with ring-diff, thumb-diff, and
      palm-diff (Spearman rho = 0.67, 0.75, and 0.74, respectively). Therefore, we
      propose the use of the CSI as not only an accurate but also a reliable method for
      diagnosing carpal tunnel syndrome.

PMID- 10918266
TI  - Correlation between quantitative EMG and muscle MRI in patients with axonal
      neuropathy.
AB  - The aim of the study was to investigate whether there are correlations between
      electromyography (EMG) data and findings in muscle magnetic resonance imaging
      (MRI). Quantitative EMG data and the amount of pathologic spontaneous activity
      (PSA) were compared with MRI signal intensities of the tibialis anterior muscles
      of 20 patients with axonal polyneuropathy and 14 healthy subjects. Using
      hierarchical regression analysis, the mean motor unit action potential (MUAP)
      size index (SI) and the amount of PSA were accurate predictors of T1-weighted
      signal intensity in MRI, an expression of fatty degeneration. The MUAP SI was
      superior to MUAP amplitude in explaining the variance of T1 signal intensity. Age
      was not a relevant factor. A high correlation was found between the amount of PSA
      and the T2-weighted signal intensity in short tau inversion recovery sequence.
      Magnetic resonance imaging demonstrates the structural changes and thus
      visualizes the outcome of the functional changes of denervation and reinnervation
      detected by EMG.

PMID- 10918267
TI  - Analysis of muscle proteins in acute quadriplegic myopathy.
AB  - We investigated the changes of muscle proteins in acute quadriplegic myopathy
      (AQM) using immunohistochemistry and stoichiometry. Cases of AQM were observed in
      which it was difficult to type muscle fibers with adenosine triphosphatase
      staining in biopsied muscle. Well-defined typing of these cases was possible by
      performing immunofluorescent staining using slow and fast skeletal troponin I
      (TnI) antibodies. By this means, small angular fibers were shown to be fast
      skeletal muscle, and myosin was absent from these muscle fibers. Actin and
      tropomyosin were maintained. Muscle protein ratios were determined by
      stoichiometry following sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      of AQM myofibril specimens from four subjects. The myosin heavy chain/actin ratio
      was significantly decreased compared with a normal control group and other
      neuromuscular diseases. These pathologic findings returned to normal during
      recovery from AQM. Thus, myosin selectively decreases, whereas actin and
      regulatory proteins located above it are maintained during AQM.

PMID- 10918268
TI  - Technique for studying conduction in the lateral cutaneous nerve of calf.
AB  - We describe a novel technique for assessing conduction in the lateral cutaneous
      nerve of the calf (LCNC), a branch of the common peroneal nerve, based on a study
      of 32 healthy subjects. Both antidromic and orthodromic techniques were used in
      each of the 64 limbs to obtain a sensory nerve action potential (SNAP) of the
      LCNC over a distance of 12 cm. In 60 limbs (93.7%) a SNAP was obtainable with
      either the antidromic or orthodromic technique. In 21 limbs (32. 8%), the SNAP
      was obtained both antidromically and orthodromically. In 33 limbs (51.6%), the
      SNAP was obtained only antidromically, and in 6 (9.4%), only orthodromically. In
      four limbs, the response was unobtainable. Mean antidromic onset latency was 2.1
      ms +/- SD 0.3, peak latency was 2.6 ms +/- SD 0.4, amplitude (without averaging)
      was 4.3 microV +/- SD 2.5, and conduction velocity was 60 m/s +/- SD 10. Mean
      orthodromic onset latency was 2.3 ms +/- SD 0.3, peak latency was 2.7 ms +/- SD
      0.3, amplitude was 5.0 microV +/- SD 2.2, and conduction velocity was 52 m/s +/-
      SD 5. Utilization of this technique allows for more detailed localization of
      common peroneal nerve injury based on whether it is proximal or distal to the
      origin of the LCNC.

PMID- 10918269
TI  - A neurophysiological grading scale for carpal tunnel syndrome.
AB  - Different ways of expressing the severity of carpal tunnel syndrome (CTS) are
      found in the existing literature and in clinical records. This paper documents
      the distribution of patients on a scale based upon the nerve conduction study
      findings, which are largely independent of the exact normal values used in any
      given laboratory and demonstrate a highly significant linear relationship between
      the neurophysiological grading and a numerical score derived from the clinical
      history. Patients with more characteristic stories of CTS generally have higher
      neurophysiological grades. The scale is as follows: normal (grade 0); very mild
      (grade 1), CTS demonstrable only with most sensitive tests; mild (grade 2),
      sensory nerve conduction velocity slow on finger/wrist measurement, normal
      terminal motor latency; moderate (grade 3), sensory potential preserved with
      motor slowing, distal motor latency to abductor pollicis brevis (APB) < 6.5 ms;
      severe (grade 4), sensory potentials absent but motor response preserved, distal
      motor latency to APB < 6. 5 ms; very severe (grade 5), terminal latency to APB >
      6.5 ms; extremely severe (grade 6), sensory and motor potentials effectively
      unrecordable (surface motor potential from APB < 0.2 mV amplitude).

PMID- 10918270
TI  - Cardiac repolarization abnormalities in multiple sclerosis: spinal cord MRI
      correlates.
AB  - Ventricular repolarization dysfunction has recently been reported in multiple
      sclerosis (MS). We evaluated ventricular repolarization dysfunction in 52 MS
      patients and looked for a relationship between corrected QT (QTc) abnormalities
      (i.e., abnormalities of QT intervals corrected for rate) and spinal cord magnetic
      resonance imaging (MRI) findings. QTc intervals were increased in MS patients
      compared with controls (P < 0.01) and were correlated with a reduction of spinal
      cord area (P < 0.01). QTc abnormalities in MS were thus associated with axonal
      loss, reflected by spinal cord atrophy, rather than demyelination.

PMID- 10918271
TI  - Treatment of myasthenia gravis with mycophenolate mofetil: a case report.
AB  - We report a patient with myasthenia gravis (MG) who had marked clinical benefit
      in response to treatment with mycophenolate mofetil as documented by serial
      quantitative measures of strength and muscle fatigue. Our patient had experienced
      either adverse side effects or a suboptimal response to the usual
      immunosuppressive agents used in MG. Mycophenolate mofetil was used in
      combination with cyclosporine and prednisone and allowed for significant
      reductions in dosage of these immunosuppressants. We conclude that mycophenolate
      mofetil deserves further study as a therapeutic agent in MG. In particular, its
      role as a steroid-sparing agent and as a drug to be used in combination
      immunotherapy in more severe or refractory cases of MG should be investigated.

PMID- 10918272
TI  - Multiple peripheral nerve compressions related to malignantly transformed
      hereditary multiple exostoses.
AB  - Autosomal dominantly transmitted hereditary multiple exostoses is an uncommon
      disorder consisting of multiple projections of bone capped by cartilage. The
      lesions are most numerous in the metaphyses of long bones but may appear on flat
      bones. Sarcomatous transformation occurs in 1-25% of patients. We report a 33
      year-old man with sciatica, previously diagnosed as hereditary multiple
      exostoses, presenting with multiple peripheral nerve compressions.
      Electrodiagnostic studies showed profound axon-loss multiple neuropathies
      involving the sciatic, superior gluteal, and inferior gluteal nerves. Magnetic
      resonance imaging of the left pelvis showed a large mass in the sacral area that
      was suggestive of a chondrosarcoma. An open intralesional excision biopsy
      confirmed chondrosarcoma transformed from chondromatosis. Excision of the lesion
      was effective in eliminating the impingement of nerves and retarding progressive
      osseous growth. We suggest that malignant transformation be suspected in cases
      with focal compression neuropathy of patients known to have multiple exostoses.
      Osteochondroma as a possible cause for compression neuropathy is discussed.

PMID- 10918273
TI  - Presentation of intravascular lymphomatosis as lumbosacral polyradiculopathy.
AB  - A 53-year-old man developed progressive sensory disturbance and weakness in the
      legs, sphincter disturbance, back pain, systemic symptoms, and pancytopenia.
      Electrophysiological tests indicated a widespread lumbosacral polyradiculopathy.
      Spinal magnetic resonance imaging and routine cerebrospinal fluid analysis showed
      minor nonspecific abnormalities. Bone marrow and liver biopsies showed
      hemophagocytosis; and polymerase chain reaction of cerebrospinal fluid, bone
      marrow, and serum suggested active infection with human herpesvirus-6. Autopsy
      revealed that his neurological symptoms resulted from intravascular lymphomatosis
      (angiotropic large cell lymphoma), a rare variant of lymphoma with predilection
      for the nervous system.

PMID- 10918274
TI  - Thalidomide neuropathy: role of F-wave monitoring.

PMID- 10918275
TI  - AAEM news and comments

PMID- 10918276
TI  - Confocal assay for invasion: use of propidium iodide fluorescence and laser
      reflectance to quantify the rate of migration of cells through a matrix.
AB  - BACKGROUND: Most assays used to measure invasion are based on manual counting of
      the number of cells that have migrated completely through commercial coated
      filters. We describe here a confocal fluorescence-imaging method that can assess
      the relative rates of invasion of cells into a matrix. METHODS: After being
      seeded on the matrix and a period of incubation, the cells are fixed and treated
      with RNase. Propidium iodide is then added to stain the double-stranded DNA. A
      confocal microscope system is used to obtain high-resolution images of the red
      propidium iodide fluorescence and laser reflectance from optical sections at
      increasing depths in the matrix. The section with high laser reflectance marks
      the top of the matrix. RESULTS: Data were calculated as the total area of red
      fluorescence above background in each section and were plotted as a percentage of
      the summed fluorescent areas in all sections. CONCLUSIONS: Because the distance
      into the matrix of the nuclei can be calculated by measuring from the reflective
      upper surface of the matrix, the method is useful for assessing the rate of cell
      migration and for comparing the ability of different cells to invade through
      different matrices under varying conditions.

PMID- 10918277
TI  - Individual cell motility studied by time-lapse video recording: influence of
      experimental conditions.
AB  - BACKGROUND: Eukaryotic cell motility plays a key role during development, wound
      healing, and tumour invasion. Computer-assisted image analysis now makes it a
      realistic task to quantify individual cell motility of a large number of cells.
      However, the influence of culture conditions before and during measurements has
      not been investigated systematically. METHODS: We have evaluated intraassay and
      interassay variations in determinations of cellular speed of fibroblastoid L929
      cells and investigated the effects of a series of physical and biological
      parameters on the motile behavior of this cell line. Cellular morphology and
      organization of filamentous actin were assessed by means of phase-contrast and
      confocal laser scanning microscopy and compared to the corresponding motility
      data. RESULTS: Cell dissociation procedure, seeding density, time of cultivation,
      and substrate concentration were shown to affect cellular speed significantly. pH
      and temperature of the medium most profoundly influenced cell motility and
      morphology. Thus, the mean cell speed was 40% lower at pH 7.25 than at pH 7.6; at
      29 degrees C, it was approximately four times lower than at 39 degrees C.
      CONCLUSION: Of the parameters evaluated, cell motility was most strongly affected
      by changes in pH and temperature. In general, changes in cell speed were
      accompanied by alterations in cell morphology and organization of filamentous
      actin, although no consistent phenotypic characteristics could be demonstrated
      for cells exhibiting high cell speed.

PMID- 10918278
TI  - Multiparameter analysis of progeny of individual cells by laser scanning
      cytometry.
AB  - BACKGROUND: Effectiveness of antitumor drugs to suppress unrestricted
      proliferation of cancer cells is commonly measured by cell clonogenicity assays.
      Assays of clonogenicity are also used in studies of stem/progenitor cells and in
      analysis of carcinogenic transformation. The conventional assays are limited to
      providing information about frequency of colonies (cloning efficiency) and do not
      reveal the qualitative (phenotype) attributes of individual colonies that may
      yield clues on mechanisms by which cell proliferation was affected by the studied
      agent. METHODS: Laser scanning cytometry (LSC) was adapted to identify and
      characterize size and phenotype of colonies of MCF-7 cells growing in microscope
      slide chambers, untreated and treated with the cytotoxic ribonuclease, onconase
      (Onc). Individual colonies were located and data representing each colony were
      segmented based on >650-nm fluorescence excited by a He-Ne laser of the cells
      whose protein was stained with BODIPY 630/650-X. The DNA of the cells was stained
      with propidium iodide (red fluorescence) whereas specific proteins (estrogen
      receptor [ER] or tumor suppressor p53) were detected immunocytochemically (green
      fluorescence), each excited by an Ar ion laser. RESULTS: A plethora of attributes
      of individual colonies were measured, such as (a) morphometric features (area,
      circumference, area/circumference ratio, DNA or protein content per area ratio),
      (b) number of cells (nuclei), (c) DNA content, (d) protein content and
      protein/DNA ratio, and (e) expression of ER or p53 per colony, per total protein,
      per nucleus or per DNA, within a colony. Also cell cycle distribution within
      individual colonies and heterogeneity of colonies with respect to all the
      measured features could be assessed. The colonies growing in the presence of Onc
      had many of the above attributes different than the colonies from the untreated
      cultures. CONCLUSIONS: Analysis of the features of cell colonies by LSC provides
      a wealth of information about the progeny of individual cells. Changes in colony
      size and phenotype, reflecting altered cell shape, cell size, colony protein/DNA
      ratio, and expression of individual proteins, may reveal mechanisms by which
      drugs suppress the proliferative capacity of the cells. This may include inducing
      growth imbalance and differentiation and modulating expression of the genes that
      may be associated with cell cycle, apoptosis, or differentiation in a progeny of
      individual cells. Extensions of LSC may make it applicable for automatic analysis
      of cloning efficiency and multiparameter analysis of cell colonies in soft agar.
      Such analyses may be useful in studies of the mechanisms and effectiveness of
      antitumor drugs, in the field of carcinogenesis, and for analyzing primary
      cultures and assessing tumor prognosis and drug sensitivity. The assay can also
      be adapted to analysis of microbial colonies.

PMID- 10918279
TI  - Characteristics of a novel deep red/infrared fluorescent cell-permeant DNA probe,
      DRAQ5, in intact human cells analyzed by flow cytometry, confocal and multiphoton
      microscopy.
AB  - BACKGROUND: The multiparameter fluorometric analysis of intact and fixed cells
      often requires the use of a nuclear DNA discrimination signal with spectral
      separation from visible range fluorochromes. We have developed a novel deep red
      fluorescing bisalkylaminoanthraquinone, DRAQ5 (Ex(lambdamax) 646 nm;
      Em(lambdamax) 681 nm; Em(lambdarange) 665->800 nm), with high affinity for DNA
      and a high capacity to enter living cells. We describe here the spectral
      characteristics and applications of this synthetic compound, particularly in
      relation to cytometric analysis of the cell cycle. METHODS: Cultured human tumor
      cells were examined for the ability to nuclear locate DRAQ5 using single and
      multiphoton laser scanning microscopy (LSM) and multiparameter flow cytometry.
      RESULTS: Multiparameter flow cytometry shows that the dye can rapidly report the
      cellular DNA content of live and fixed cells at a resolution level adequate for
      cell cycle analysis and the cycle-specific expression of cellular proteins (e.g.,
      cyclin B1). The preferential excitation of DRAQ5 by laser red lines (633/647 nm)
      was found to offer a means of fluorescence signal discrimination by selective
      excitation, with greatly reduced emission overlap with UV-excitable and visible
      range fluophors as compared with propidium iodide. LSM reveals nuclear
      architecture and clearly defines chromosomal elements in live cells. DRAQ5 was
      found to permit multiphoton imaging of nuclei using a 1,047-nm emitting mode
      locked YLF laser. The unusual spectral properties of DRAQ5 also permit live cell
      DNA analysis using conventional 488 nm excitation and the single-photon imaging
      of nuclear fluorescence using laser excitation between 488 nm and low infrared
      (IR; 780 nm) wavelengths. Single and multiphoton microscopy studies revealed the
      ability of DRAQ5 to report three-dimensional nuclear structure and location in
      live cells expressing endoplasmic reticulum targeted-GFP, MitoTracker-stained
      mitochondria, or a vital cell probe for free zinc (Zinquin). CONCLUSION: The
      fluorescence excitation and emission characteristics of DRAQ5 in living and fixed
      cells permit the incorporation of the measurement of cellular DNA content into a
      variety of multiparameter cytometric analyses.

PMID- 10918280
TI  - Detection of receptor clustering by flow cytometric fluorescence anisotropy
      measurements.
AB  - BACKGROUND: Perrin equation suggests an alternative way for the accurate energy
      transfer determination on a cell-by-cell basis by measuring polarized donor
      intensities in a conventional flow cytometer. METHODS: The relationship between
      energy transfer and fluorescence anisotropy of the donor was investigated by flow
      cytometric generation of Perrin-lifetime plots of fluorescent antibody-labeled
      MHC class I and class II molecules on the surface of living cells. The energy
      transfer reduced the fluorescence lifetime of the donor. RESULTS: Perrin plots
      have proven to be sensitive to the segmental mobility of the labeling dye and
      that of antibodies of different isotypes, and homo-transfer due to the multiple
      labeling of antibodies. A method demonstrating the feasibility of energy transfer
      determination by measuring anisotropy enhancement of the donor is presented. Flow
      cytometric histograms of the donor anisotropy and of the deduced energy transfer
      efficiency are shown, indicating clustering of MHC class I and class II molecules
      on the surface of human T lymphoblasts. In the Appendix, a method for the
      simultaneous determination of both energy transfer efficiency and donor
      fluorescence anisotropy, without need for G-factor measurement, is also
      presented. CONCLUSIONS: We demonstrate that energy transfer efficiency, i.e.,
      proximity, between suitably selected donor and acceptor, and the rotational
      relaxation of the donor, i.e., donor mobility, can be simultaneously measured in
      a flow cytometer.

PMID- 10918281
TI  - Magnetophoretic mobilities correlate to antibody binding capacities.
AB  - METHODS: A methodology and a mathematical theory have been developed, which allow
      quantitation of the expression levels of cellular surface antigens using
      immunomagnetic labels and cell tracking velocimetry (CTV) technology. RESULTS:
      Quantum Simply Cellular (QSC) microbeads were immunomagnetically labeled with
      anti-CD2 fluorescein isothiocyanate (FITC) antibodies and anti-FITC MACS
      paramagnetic nanoparticles. Magnetophoretic mobility has been defined as the
      magnetically induced velocity of the labeled cell or microbead divided by the
      magnetophoretic driving force, proportional to the magnetic energy density
      gradient. DISCUSSION: Using computer imaging and processing technology, the
      mobility measurements were accomplished by microscopically recording and
      calculating the velocity of immunomagnetically labeled QSC microbeads in a nearly
      constant magnetic energy gradient. A calibration curve correlating the measured
      magnetophoretic mobility of the immunomagnetically labeled microbeads to their
      antibody binding capacities (ABC) has been obtained. CONCLUSION: The results, in
      agreement with theory, indicate a linear relationship between magnetophoretic
      mobility and ABC for microbeads with less than 30,000 ABC. The mathematical
      relationships and QSC standardization curve obtained allow determination of the
      number of surface antigens on similarly immunomagnetically labeled cells.

PMID- 10918282
TI  - Cell surface receptor-antibody association constants and enumeration of receptor
      sites for monoclonal antibodies.
AB  - BACKGROUND: Fluorescent markers (labeled antibodies) and flow cytometry are used
      to enumerate the average number of receptors (antigens) on formed bodies (cells)
      in whole blood by using a new method that avoids the extra steps of separating
      bound from unbound fluorescent markers or the use of external standards. METHODS:
      Mean channel fluorescence intensities of equilibrated marker-cell suspension
      mixtures, total concentrations of marker, and targeted cell counts obtained by
      standard cytometry procedures are used to complete the analyses for receptors per
      cell. Also, flow cytometric assays using competitive binding between fluorescent
      marker (CD4-RD1, CD8-FITC, CD3-FITC, CD3-RD1) and unlabeled antibody (CD4, CD8,
      CD3, CD3-dextran) for receptors on white blood cells in whole blood are described
      for determination of relative and specific binding constants of unlabeled/labeled
      antibody for targeted receptors. RESULTS: Ranges that were obtained for receptors
      per cell (lymphocytes) in normal blood donors were as follows: CD4, 4.9 x 10(4)
      1.5 x 10(5); CD8, 5.0 x 10(5)-2.1 x 10(6); CD3, 6.6-7.8 x 10(5). Binding
      constants were highest for unlabeled CD4 antibody, 2. 7 x 10(10)-2.1 x 10(12) M(
      1), and then unlabeled CD3 antibody, 1.1 x 10(10)-1.9 x 10(11) M(-1). FITC- and
      RD1-labeled antibodies typically had binding constants that were 10-to 100-fold
      lower than the native antibodies. CONCLUSIONS: Values of receptors per cell and
      binding constants obtained by the new method from flow cytometric analyses of
      mixtures of whole blood with FITC- or RD1-labeled CD4, CD8, and CD3 antibodies
      compare well with literature values determined by other methods.

PMID- 10918283
TI  - Ultraviolet-induced detection of halogenated pyrimidines: simultaneous analysis
      of DNA replication and cellular markers.
AB  - BACKGROUND: We describe a new nonenzymatic methodology that allows the
      simultaneous detection of DNA replication and other cellular markers such as
      immunophenotyping. DNA replicating cells are identified by their incorporation of
      halogenated thymidine analogs, e.g., 5-bromo-deoxyuridine (BrdUrd). METHODS:
      Irradiation with ultraviolet (UV)-B or UV-A light in the presence of Hoechst
      33258 and subsequent treatment with a hypotonic buffer makes BrdUrd accessible to
      monoclonal antibodies (mAb), thus allowing its sensitive detection. RESULTS: The
      photolysis of BrdUrd in DNA with UV light is sequence dependent and results in
      DNA damage, allowing the detection of remaining BrdUrd using hypotonic
      conditions. However, treatment with other inducers of single or double- strand
      breaks of DNA such as gamma irradiation or hydrogen peroxide did not allow BrdUrd
      detection. The new methodology is compatible with both mild crosslinking
      fixation, i.e., aldehydes, or coagulative fixation, i.e., alcohols. The
      successful identification of CD34+, CD138+, or CD19+ cells out of heterogeneous
      cell suspensions and their cell-cycle analysis are described. Results correlated
      very well with acid denaturation (r = 0.972). The average coefficient of
      variation (CV) of G(1) in the DNA histogram was smaller than 5%, resulting in
      good preservation of DNA distribution. Also, the signal-to-noise ratio was almost
      twice as high as for 2N acid denaturation, facilitating convenient discrimination
      of BrdUrd-positive cells. CONCLUSIONS: In contrast to previous approaches, this
      methodology eliminates the need for any additional enzymatic treatment such as
      DNA digestion or strand-break labeling after UV irradiation. The method is fast,
      convenient, and inexpensive and should be able to promote the use of halogenated
      pyrimidines in basic and clinical research of cancer, immunology, and
      pharmacology.

PMID- 10918284
TI  - Flow cytometric analysis of the Vbeta repertoire in healthy controls.
AB  - BACKGROUND: Analysis of the T-cell receptor (TCR)-Vbeta repertoire has been used
      for studying selective T-cell responses in autoimmune disease, alloreactivity in
      transplantation, and protective immunity against microbial and tumor antigens.
      For the interpretation of these studies, we need information about the Vbeta
      repertoire usage in healthy individuals. METHODS: We analyzed blood T-lymphocyte
      (sub)populations of 36 healthy controls (age range: from neonates to 86 years)
      with a carefully selected most complete panel of 22 Vbeta monoclonal antibodies,
      which together recognized 70-75% of all blood TCRalphabeta(+) T lymphocytes.
      Subsequently, we developed a six-tube test kit with selected Vbeta antibody
      combinations for easy and rapid detection of single ("clonal") Vbeta domain usage
      in large T-cell expansions. RESULTS: The mean values of the Vbeta repertoire
      usage were stable during aging in blood TCRalphabeta(+) T lymphocytes as well as
      in the CD4(+) and CD8(+) T-cell subsets, although the standard deviations
      increased in the elderly. The increased standard deviations were caused by the
      occurrence of oligoclonal T-cell expansions in the elderly, mainly consisting of
      CD8(+) T lymphocytes. The 15 detected T-cell expansions did not reach 40% of
      total TCRalphabeta(+) T lymphocytes and represented less than 0.4 x 10(9) cells
      per liter in our study. Vbeta usage of the CD4(+) and CD8(+) subsets was
      comparable for most tested Vbeta domains, but significant differences (P < 0.01)
      between the two subsets were found for Vbeta2, Vbeta5.1, Vbeta6.7, Vbeta9.1, and
      Vbeta22 (higher in CD4(+)), as well as for Vbeta1, Vbeta7.1, Vbeta14, and Vbeta23
      (higher in CD8(+)). Finally, single Vbeta domain expression in large T-cell
      expansions can indeed be detected by the six-tube test kit. CONCLUSIONS: The
      results of our study can now be used as reference values in studies on
      distortions of the Vbeta repertoire in disease states. The six-tube test kit can
      be used for detection of single Vbeta domain expression in large T-cell
      expansions (>2.0 x 10(9)/l), which are clinically suspicious of T-cell leukemia.

PMID- 10918285
TI  - Quantitative fluorescence cytometric analysis of Bcl-2 levels in tumor cells
      exhibiting a wide range of inherent Bcl-2 protein expression: correlation with
      Western blot analysis.
AB  - BACKGROUND: A protocol to measure a wide range of Bcl-2 protein expression using
      quantitative fluorescence cytometry (QFCM) in different cell types was developed
      for use with flow cytometry. Bcl-2 measurements obtained by flow cytometry were
      correlated with Western blot Bcl-2 measurements to confirm specificity of the Bcl
      2-FITC staining. This protocol was applied to measure absolute levels of Bcl-2
      protein in different tumor cell lines including Bcl-2-transfected breast
      carcinoma cell lines and in peripheral blood lymphocytes (PBL). METHODS: HL-60,
      K562, DOHH2, Jurkat, MDA435/LCC6, MCF7 cell lines, and PBL derived from normal
      donors were fixed, permeabilized, stained with anti-Bcl-2-FITC antibody and
      evaluated by QFCM. In parallel, the same cells were evaluated for Bcl-2 protein
      expression by Western blot analysis. Mitochondrial localization of anti-Bcl-2
      FITC antibody inside cells was confirmed using fluorescence imaging microscopy.
      RESULTS: Bcl-2 expression in different cell types could be accurately quantified
      based on antibody-binding capacity (ABC) ranging from 12.6 x 10(3) antibody
      binding sites in HL-60 cells to 1.64 x 10(6) antibody-binding sites in a Bcl-2
      transfected MDA435/LCC6 clone. The data from flow cytometry analysis correlated
      well with Western analysis (R(2) = 0.78). Bcl-2-FITC staining colocalized with
      dyes specific for mitochondria. CONCLUSIONS: The Bcl-2 staining protocol
      described here was shown to be specific, sensitive, and it was able to provide
      higher resolution as well as more reproducible quantitation of Bcl-2 protein
      content in cells when compared with Western blot methods. Quantitation of Bcl-2
      content in cells by QFCM may be useful for monitoring Bcl-2 expression in cells
      undergoing various treatments in vitro and in vivo.

PMID- 10918286
TI  - Flow cytometric assessment of allopurinol susceptibility in Leishmania infantum
      promastigote.
AB  - BACKGROUND: Leishmaniasis is a major tropical and subtropical parasitic disease.
      Sodium stibogluconate, N-methyl -D-glucamine antimoniate, amphotericin B,
      pentamidine, and ketoconazole are drugs used to treat this disease. Some of these
      drugs cause severe adverse side effects and treatment failures are common.
      Allopurinol, a purine analog, has been used to treat leishmaniasis, alone or
      combined with the previously mentioned drugs. Low cost, ease of administration
      (oral), and lack of toxicity make allopurinol a particularly appealing candidate.
      METHODS: The effect of allopurinol on Leishmania infantum
      (MCAN/ES/89/IPZ229/1/89, zymodeme MON1) wild-type promastigotes (wt-p229), and an
      altered form of these promastigotes (allo-p229) resulting from long term in vitro
      exposure to allopurinol, was determined by [(3)H]-thymidine incorporation assays
      and by diverse flow cytometric approaches. RESULTS: Allopurinol arrested the
      proliferative capacity of wt-p229 promastigotes, reduced the proportion of viable
      cells, and decreased their total protein content. In contrast, allo-p229
      promastigote proliferation was only slightly decelerated and the proportion of
      viable cells and the protein content were not affected by the allopurinol
      treatment. CONCLUSIONS: The flow cytometry approach allowed us to demonstrate
      differences in allopurinol susceptibility of the two promastigote forms,
      expanding the spectrum of flow cytometry applications in studies of parasite
      resistance.

PMID- 10918288
TI  - Selective photothermolysis in skin by using subcutaneous optical fibers.
AB  - BACKGROUND AND OBJECTIVE: Vascular selective photothermolysis has been shown to
      be effective in treating hypertrophic scars. Performing selective
      photothermolysis on the vasculature deep within thick scars requires new methods
      for delivering laser energy. It is the objective of this study to model the use
      of subcutaneous fiber optics to perform selective photothermolysis in skin as a
      possible aid in the treatment of thick scars. STUDY DESIGN/MATERIALS AND METHODS:
      A Monte Carlo simulation was performed to study the expected region of vascular
      necrosis in a two layer skin model when 585-nm radiation is delivered into the
      dermis by means of subcutaneous optical fibers. RESULTS: The extent of vascular
      necrosis is independent of fiber diameter for a fixed total energy. A fiber
      penetrating barely below the epidermis decreases the maximum epidermal fluence by
      more than an order of magnitude relative to a superficial beam. Using four fibers
      simultaneously can significantly increase the depth of vascular necrosis.
      CONCLUSIONS: Small diameter fibers are optimum if the maximum fluence tolerable
      in the dermis is not a limiting factor. Shallowly inserted fibers can
      significantly decrease epidermal damage to dark-skinned patients undergoing laser
      therapy.

PMID- 10918287
TI  - In vivo experimental evaluation of skin remodeling by using an Er:Glass laser
      with contact cooling.
AB  - BACKGROUND AND OBJECTIVE: Selective dermal remodeling consists of inducing
      collagen tightening, neocollagen synthesis, or both, without damage to the
      overlying epidermis. This experimental study aimed to evaluate an Er:Glass laser
      emitting at 1.54 micrometer combined with contact cooling to target the upper
      dermis while protecting the epidermis. STUDY DESIGN/MATERIALS AND METHODS: Male
      hairless rats were used for the study. Different fluences (26-30 J/cm(2)) by
      using single 3-ms pulse irradiation or pulse train irradiation (1.1 J, 3 Hz) and
      different cooling temperatures (+5 degrees C, 0 degrees C, -5 degrees C) were
      screened with clinical examination and histologic evaluation at 1, 3, and 7 days
      after laser irradiation. RESULTS: The clinical effects were clearly dose and
      temperature cooling dependent. It seemed that single pulse irradiation led to
      epidermal whitening in most cases, whatever the cooling temperature. Conversely,
      pulse train irradiation showed reproducible epidermal preservation and
      confinement of the thermal damage into the dermis. New collagen synthesis was
      confirmed by a marked fibroblastic proliferation, detected in the lower dermis at
      day 3 and clearly seen in the upper dermis at day 7. CONCLUSION: This new laser
      seems to be a promising new tool for the treatment of skin laxity, solar
      elastosis, facial rhytides, and mild reduction of wrinkles.

PMID- 10918289
TI  - Radio frequency transmyocardial revascularization enhances angiogenesis and
      causes myocardial denervation in canine model.
AB  - BACKGROUND AND OBJECTIVE: Transmyocardial revascularization (TMR) relieves angina
      and improves exercise tolerance in patients. Angiogenesis and myocardial
      denervation have been proposed as factors contributing to these benefits. To test
      whether radio frequency transmyocardial revascularization (RF-TMR) enhances
      angiogenesis and causes myocardial denervation. STUDY DESIGN/MATERIALS AND
      METHODS: RF-TMR channels were created in 12 dogs which survived up to 4 weeks.
      Bromodeoxyuridine was administered subcutaneously to mark proliferating cells as
      an assay of angiogenesis. Western blot analysis of tyrosine hydroxylase and blood
      pressure response to topical bradykinin were used as indices of myocardial
      denervation. RESULTS: RF-TMR increased local vascularity by an average of 50%,
      whereas the rate of vascular cell proliferation was tripled over that of the
      untreated region. Changes in mean arterial pressure with bradykinin and tyrosine
      hydroxylase content were significantly decreased in RF-TMR regions as compared
      with normal myocardium in the same hearts. CONCLUSION: RF-TMR enhances
      angiogenesis and causes myocardial denervation in canine myocardium as with laser
      TMR.

PMID- 10918290
TI  - Ventricular remodeling after acute myocardial infarction: effect of low-intensity
      laser irradiation.
AB  - BACKGROUND AND OBJECTIVE: Low-intensity laser irradiation is claimed to enhance
      wound healing. Healing after myocardial infarction results in ventricular
      enlargement and wall thinning. If laser treatment accelerated cardiac healing, we
      speculated that ventricular remodeling would be attenuated. STUDY
      DESIGN/MATERIALS AND METHODS: In vitro, fibroblasts were irradiated for 1 minute
      twice a day for 4 days (5 mW; wavelength, 780 nm). One day after infarction, rats
      were randomly assigned to 5 or 10 mW transdermal irradiation twice a day for 4
      days or to sham. One week after infarction, we measured the remodeling
      parameters; cavity volume, infarct thickness, and vascular structure, and the
      healing parameters; collagen content and inflammation. RESULTS: Laser-treated
      fibroblasts occupied more area than controls. Hearts receiving the 10 mW
      treatment had smaller volumes than sham hearts. Laser treatment reduced infarct
      thinning and preserved arterial lumen area; however, collagen was not increased
      and inflammation was inhibited. CONCLUSIONS: Low-intensity irradiation attenuated
      infarct-associated remodeling. In contrast to expectations from in vitro study,
      these effects were not a result of enhanced healing.

PMID- 10918291
TI  - Low-power laser light in the healing of burns: a comparison between two different
      wavelengths (635 nm and 690 nm) and a placebo group.
AB  - BACKGROUND AND OBJECTIVE: Studies on the influence of low-power laser light on
      wound healing have shown inconsistent results, or, as in the case of burns, are
      very scarce. We have studied the effects of two different low-power diode laser
      lights on the healing of burns in rats. STUDY DESIGN/MATERIALS AND METHODS:
      Thirty rats were burned on both flanks and randomly allocated to one of three
      study groups. In group A, both wounds remained untreated; in groups B and C, one
      wound each was irradiated with 635 nm or 690 nm laser light (1.5 J/cm(2)),
      whereas the other wound remained untreated. Diameter, redness, and edema of the
      wounds were examined daily. RESULTS: Between and within groups, diameter,
      redness, and edema of the wounds were similar throughout the entire observation
      period. Irradiation of the burns did not accelerate wound healing when compared
      with control wounds. CONCLUSION: We conclude that neither 690 nm nor 635 nm low
      power laser light produced any beneficial effects on the healing processes of
      burns in rats.

PMID- 10918292
TI  - Inadvertent corneal burn by using indirect wide-field contact lenses and
      different laser beam delivery systems during experimental fundus
      photocoagulation.
AB  - BACKGROUND AND OBJECTIVE: At fundus photocoagulation by using a wide-field
      indirect contact lens, the laser radiant exposure may be increased at the
      anterior segment of the eye. We examined the likelihood of producing inadvertent
      corneal burn by using parfocal and sharped edge defocus laser delivery systems
      with various indirect contact lenses. STUDY DESIGN/MATERIALS AND METHODS: The two
      laser delivery systems were used with four lenses of different viewing angles
      during fundus photocoagulation in a total 44 eyes of rabbits. RESULTS: By using
      the lenses, the parfocal system increased corneal radiant exposure more than did
      the sharped edge defocus system. By using the Widefield PRP 165 lens of the
      widest viewing angle, there was no difference between the two systems in the
      corneal burns produced. CONCLUSION: Some indirect contact lenses used in
      combination with the parfocal system caused inadvertent corneal burns more
      readily than did the same lenses in combination with the sharped edge defocus
      system.

PMID- 10918293
TI  - Carbon dioxide laser turbinate surgery for chronic obstructive rhinitis.
AB  - BACKGROUND AND OBJECTIVE: The argon laser was first used to treat chronic
      obstructive rhinitis. Several other surgical lasers were later used to perform
      inferior turbinotomy. What is the ideal laser for turbinate surgery? STUDY
      DESIGN/MATERIALS AND METHODS: CO(2) laser with its longer wavelength (10.6
      micrometer) scatters less on tissues, is less harmful than the other surgical
      lasers, minimizes local edema with very little damage to the nearby mucosa, and
      achieves excellent haemostasis. But CO(2) laser energy delivered through a
      fiberoptic cable is partially absorbed by the transmitting fiber. CO(2) laser
      delivered through surgical microscope obviates this problem, and a special self
      retaining nasal speculum allows the surgeon to have both hands free to more
      easily perform inferior laser turbinotomy, creating a deep groove along the
      turbinate body. RESULTS: The laser vaporized tissues formed scar tissue, reduced
      turbinate bulk, restored nasal flow, and improved other symptoms: rhinorrhoea,
      sneezing, headache with a statistically significant reduction in total nasal
      airway resistance (NAR), P < 0.005, at 2 year follow-up. CONCLUSION: The CO(2)
      laser delivered through surgical microscope with the help of a self-retaining
      nasal speculum can be deemed a useful laser for turbinate surgery.

PMID- 10918294
TI  - Laser skin welding: in vivo tensile strength and wound healing results.
AB  - BACKGROUND AND OBJECTIVE: Laser skin welding was investigated as a general model
      for laser tissue closure. Scanned delivery of near-infrared laser radiation in
      combination with a dye can produce strong welds with limited thermal damage.
      STUDY DESIGN/MATERIALS AND METHODS: Two-centimeter-long, full-thickness incisions
      were made on the backs of guinea pigs. Wounds were closed either by laser welding
      or sutures and then biopsied at 0, 3, 6, 10, 14, 21, and 28 days postoperatively.
      Welding was achieved by using continuous-wave, 1. 06-micrometer, Nd:YAG laser
      radiation scanned over the incisions to produce a dwell time of approximately 80
      msec. The cooling time between scans was fixed at 8 seconds. A 4-mm-diameter
      laser spot was maintained during the experiments, and the power was kept constant
      at 10 W. The operation time was fixed at 10 minutes per incision. India ink was
      used as an absorber of the laser radiation at the weld site, and clamps were used
      temporarily to appose the incision edges. RESULTS: Acute weld strengths of 2.1 +/
      0.7 kg/cm(2) were significantly higher than suture apposition strengths of 0.4
      +/- 0.1 kg/cm(2) (P < 0.01), and weld strengths continued to increase over time.
      Lateral thermal damage in the laser welds was limited to 200 +/- 40 micrometer
      near the epidermal surface with less thermal damage deeper within the dermis.
      CONCLUSION: Our welding technique produced higher weld strengths and less thermal
      damage than reported in previous skin welding studies and may represent an
      alternative to sutures.

PMID- 10918295
TI  - Morphometric and functional results after CO(2) laser welding of nerve
      coaptations.
AB  - BACKGROUND AND OBJECTIVE: Several reports describe nerve coaptations by laser
      welding in combination with stay sutures and bonding material. This study was
      undertaken to obtain functional and morphologic information by using a nerve
      coaptation technique by epineurial CO(2) laser welding only. STUDY
      DESIGN/MATERIALS AND METHODS: The sciatic nerves of 24 rats were transected and
      epineurially coapted with the CO(2) laser at 60 mW or with microsutures as a
      control. Walking track analysis were carried out to evaluate the functional
      recovery, and the nerves were harvested for histology after 6 months of
      regeneration. RESULTS: None of the 24 nerves showed dehiscence of the
      coaptations, and all showed good nerve fiber regeneration. Better results were
      obtained for the functional evaluation of the sciatic function index (P < 0.02)
      and the toe spread index (P < 0.04) from the laser nerve coaptations. Likewise,
      the morphologic evaluations of the fiber density (P < 0.04) and area fraction (P
      < 0.002) were better in the laser group. CONCLUSION: CO(2) laser welded nerve
      coaptations are as successful as their sutured counterparts and may become a
      promising alternative in clinical practice.

PMID- 10918296
TI  - Biodegradable polymer film reinforcement of an indocyanine green-doped liquid
      albumin solder for laser-assisted incision closure.
AB  - BACKGROUND AND OBJECTIVE: The purpose of this study was to determine whether
      solid material reinforcement of a liquid albumin solder coagulum could improve
      the cohesive strength of the solder and, thus, the ultimate breaking strength of
      the incision repair in vitro. STUDY DESIGN/MATERIALS AND METHODS: A 50%(w/v)
      bovine serum albumin solder with 0.5 or 2.5 mg/ml indocyanine green (ICG) dye was
      used to repair an incision in bovine aorta. The solder was coagulated with an 806
      nm continuous wave diode laser. A 50-micrometer-thick poly(DL-lactic-co-glycolic
      acid) film was used to reinforce the solder (the controls had solder but no
      reinforcement). Acute breaking strengths were measured, and the data were
      analyzed by Student's t-test. RESULTS: Observations of the failure modes indicate
      cohesive strength reinforcement of the test specimens vs. the controls. The 2.5
      mg/ml ICG reinforced solder was stronger than the controls without reinforcement
      (P < 0.05) for all laser powers tested. There was no difference between the test
      specimens and the controls with 0.5 mg/ml ICG solder for low laser powers, but at
      higher laser powers, the reinforced solder was stronger than the controls (P <
      0.05). CONCLUSION: Reinforcement of liquid albumin solders in laser-assisted
      incision repair seems to have advantages in terms of acute breaking strength over
      conventional methods that do not reinforce the cohesive strength of the solder.

PMID- 10918297
TI  - Welding characteristics of different albumin species with and without fatty
      acids.
AB  - BACKGROUND AND OBJECTIVE: Albumin solders from different species have been used
      for laser tissue welding without a complete understanding of possible differences
      between them. The breaking strength of four different species of serum albumin
      (human, bovine, porcine, and canine), both fatty acid containing (FAC) and fatty
      acid free (FAF), was determined to evaluate the welding ability of each type of
      albumin. STUYDY DESIGN/MATERIALS AND METHODS: Acute breaking strengths were
      determined on canine small bowel by using 50% albumin (FAF and FAC) from human,
      bovine (BSA), porcine, and canine species. RESULTS: BSA-FAC and BSA-FAF had a
      significantly higher (P < 0.05) breaking strength than all other groups;
      furthermore, BSA-FAC was significantly higher (P < 0.05) than BSA-FAF. There was
      no significant difference in breaking strength when FAF albumin was compared with
      FAC albumin from humans, pigs, or dogs. CONCLUSION: These experimental results
      show that species-specific and fatty acid-specific differences exist when these
      albumin solders are used for laser tissue welding. This finding suggests that
      modifications in albumin could be used to improve results through decreased
      thermal damage and increased weld strength.

PMID- 10918298
TI  - Retinal stem cells in vertebrates.
AB  - In fish and amphibia, retinal stem cells located in the periphery of the retina,
      the ciliary marginal zone (CMZ), produce new neurons in the retina throughout
      life. In these species, the retina grows to keep pace with the enlarging body.
      When birds or mammals reach adult proportions, however, their retinas stop
      growing so there appears to be no need for such a proliferative area with stem
      cells. It is a surprise, therefore, that recent data suggest that a region
      similar to the CMZ of fish and amphibia exists in the postnatal chick and the
      adult mouse.

PMID- 10918299
TI  - Regulation of activin's access to the cell: why is mother nature such a control
      freak?
AB  - Activin A is a pluripotent growth factor with important roles in development,
      erythropoiesis and the local regulation of many tissues. At the post
      translational level, the amount of activin A produced by cells may be modulated
      through the diversion of activin A subunits into the formation of inhibin or
      other activins containing heterodimeric forms. Once assembled, activin interacts
      with various low- and high-affinity binding proteins, such as follistatin and
      alpha(2)-macroglobulin, that have consequences for receptor availability. In
      common with other TGFbeta family members, activin signals through pairs of type I
      and II receptor kinases and the Smad intracellular signalling cascade. Other
      checkpoints have been identified such as the recently identified pseudoreceptor,
      BAMBI. These emerging findings point to a tightly coordinated regulation of the
      exposure of a cell or tissue to activin, consistent with the low amounts of this
      potent factor that are necessary to modulate cellular responses.

PMID- 10918301
TI  - Environmental signals and cell fate specification in premigratory neural crest.
AB  - Neural crest cells are multipotent progenitors, capable of producing diverse cell
      types upon differentiation. Recent studies have identified significant
      heterogeneity in both the fates produced and genes expressed by different
      premigratory crest cells. While these cells may be specified toward particular
      fates prior to migration, transplant studies show that some may still be capable
      of respecification at this time. Here we summarize evidence that extracellular
      signals in the local environment may act to specify premigratory crest and thus
      generate diversity in the population. Three main classes of signals-Wnts,
      BMP2/BMP4 and TGFbeta1,2,3-have been shown to directly influence the production
      of particular neural crest cell fates, and all are expressed near the
      premigratory crest. This system may therefore provide a good model for
      integration of multiple signaling pathways during embryonic cell fate
      specification.

PMID- 10918300
TI  - The EGF receptor: a nexus for trafficking and signaling.
AB  - Ligand binding to the EGF receptor initiates both the activation of mitogenic
      signal transduction pathways plus trafficking events that relocalize the receptor
      on the cell surface and within intracellular compartments. The trafficking
      compartments include caveolae, clathrin-coated pits, and various endosome
      populations prior to receptor degradation in lysosomes. Evidence is presented
      that distinct signaling pathways are initiated from these different compartments.
      These include the Ras/MAP kinase cascade and the PLC-dependent hydrolysis of PI
      4,5 P(2). Multiple tyrosine kinase substrates that facilitate EGF receptor
      trafficking between these various compartments, as well as the participation of
      phosphoinositides and Ras-like G proteins in the trafficking pathway are also
      described.

PMID- 10918302
TI  - Ligand binding and nuclear receptor evolution.
AB  - Nuclear receptors form a superfamily of ligand-activated transcription factors
      that regulate various physiological functions, from development to homeostasis,
      in metazoans. The superfamily contains not only receptors for known ligands but
      also a large number of so-called orphan receptors for which ligands do not exist
      or have not been identified. The evolution of ligand-binding capacity of nuclear
      receptors may involve either secondary loss in orphan receptors, or evolutionary
      acquisition of ligand-binding capacity in liganded receptors. In this review, we
      present arguments from phylogenetic, functional and structural studies that
      support the hypothesis that there have been several independent gains of ligand
      binding ability of nuclear receptors during metazoan evolution.

PMID- 10918303
TI  - Roles of BRCA1 and its interacting proteins.
AB  - Germline mutations of BRCA1 predispose women to breast and ovarian cancers. BRCA1
      contains several functional domains that interact directly or indirectly with a
      variety of molecules, including tumor suppressors (p53, RB, BRCA2 and ATM),
      oncogenes (c-Myc, casein kinase II and E2F), DNA damage repair proteins (RAD50
      and RAD51), cell-cycle regulators (cyclins and cyclin-dependent kinases),
      transcriptional activators and repressors (RNA polymerase II, RHA, histone
      deacetylase complex and CtIP) and others. Mounting evidence indicates that these
      physical associations are not artifacts; rather, BRCA1 is likely to serve as an
      important central component in multiple biological pathways that regulate cell
      cycle progression, centrosome duplication, DNA damage repair, cell growth and
      apoptosis, and transcriptional activation and repression. This review examines
      our understanding of the significance of the interactions between BRCA1 and other
      proteins, through which BRCA1 maintains genome integrity and represses tumor
      formation. Published 2000 John Wiley & Sons, Inc.

PMID- 10918304
TI  - DNA topology and the thermal stress response, a tale from mesophiles and
      hyperthermophiles.
AB  - During heat shock and cold shock, plasmid DNA supercoiling changes transiently
      both in mesophilic bacteria and in hyperthermophilic archaea, despite a different
      overall topology (negative supercoiling versus relaxation to positive
      supercoiling). Transient changes in DNA supercoiling might be essential to
      generate the stress response, but they could also be a consequence of the
      physical effects of temperature on cellular components. Indeed, both appear
      intertwined. Comparison of the mechanisms acting in the two biological systems
      suggests that the dependence on temperature of the activity of different DNA
      topoisomerases, as well as of protein binding, are key factors for the control of
      DNA topology during stress, which may in turn be relevant for the expression of
      stress-induced genes.

PMID- 10918305
TI  - Glial strategy for metabolic shuttling and neuronal function.
AB  - Glial cells serve a variety of functions in nervous systems, some of which are
      activated by neurotransmitters released from neurons. Glial cells respond to
      these neurotransmitters via receptors, but also take up some of the transmitters
      to help terminate the synaptic process. Among these, glutamate uptake by glial
      cells is pivotal to avoid transmitter-mediated excitotoxicity. Here, a new model
      is proposed in which glutamate uptake via the excitatory amino acid transporter
      (EAAT) is functionally coupled to other glial transporters, in particular the
      sodium-bicarbonate cotransporter (NBC) and the monocarboxylate transporter (MCT),
      as well as other glial functions, such as calcium signalling, a high potassium
      conductance and CO(2) consumption. The central issue of this hypothesis is that
      the shuttling of sodium ions and acid/base equivalents, which drive the
      metabolite transport across the glial membrane, co-operate with each other, and
      hence save energy. As a result, glutamate removal from synaptic domains and
      lactate secretion serving the energy supply to neurons would be facilitated and
      could operate with greater capacity.

PMID- 10918306
TI  - Pattern formation by local self-activation and lateral inhibition.
AB  - In 1972, we proposed a theory of biological pattern formation in which
      concentration maxima of pattern forming substances are generated through local
      self-enhancement in conjunction with long range inhibition. Since then, much
      evidence in various developmental systems has confirmed the importance of
      autocatalytic feedback loops combined with inhibitory interaction. Examples are
      found in the formation of embryonal organizing regions, in segmentation, in the
      polarization of individual cells, and in gene activation. By computer
      simulations, we have shown that the theory accounts for much of the regulatory
      phenomena observed, including signalling to regenerate removed parts. These self
      regulatory features contribute to making development robust and error-tolerant.
      Furthermore, the resulting pattern is, to a large extent, independent of the
      details provided by initial conditions and inducing signals.

PMID- 10918307
TI  - ICP0, a regulator of herpes simplex virus during lytic and latent infection.
AB  - Cold sores produced by HSV-1 infection are an annoying but trivial recurrent
      problem for most of us, but the virus can also cause more serious disease.
      Episodes of active HSV-1 infection, in response to stress or sunlight, are
      possible because the virus establishes a latent infection in neurones which can
      not be eliminated. Since vigorous transcription from the whole viral genome
      during lytic infection contrasts with almost complete quiescence during latency,
      the mechanisms controlling HSV-1 gene expression have come under close scrutiny.
      These studies have demonstrated that the viral immediate-early protein ICP0, a
      promiscuous activator of gene expression, is required for efficient initiation of
      lytic infection and reactivation from latency. It is proposed that in the absence
      of functional ICP0, a cellular repression mechanism silences viral transcription.
      ICP0 appears to counteract this process by stimulating the degradation of a
      number of cellular proteins via the ubiquitin-proteasome pathway.

PMID- 10918308
TI  - IUBMB updates Ph.D. standards.
AB  - The Education Committee of the International Union of Biochemistry (IUB, but
      IUBMB since 1991) published its report on "Standards for the Ph.D. Degree in
      Biochemistry and Molecular Biology" in 1989. Developments since then have led to
      the disappearance of the traditional demarcations between many of the biological
      disciplines, while information technology and bioinformatics have revolutionized
      the analysis, storage, and communication of scientific data. To meet these
      challenges, that report has now been revised through a broad interdisciplinary
      and international consultation. This has led to the recent publication, on behalf
      of the same Committee, of "Standards for the PhD Degree in the Molecular
      Biosciences". Like its predecessor this revised report not only defines in
      behavioural terms the qualities and skills expected of doctoral graduates by the
      international community of molecular bioscientists but also offers useful
      suggestions and advice as to how those skills can be developed and maximized. In
      addition, it discusses various topics related to doctoral education.

PMID- 10918310
TI  - Digestive proteinase activity in corn earworm (Helicoverpa zea) after molting and
      in response to lowered redox potential.
AB  - Insect digestive proteinases are often strongly influenced by ambient
      physicochemical conditions, such as pH, ionic strength, and oxidation-reduction
      potential. Although the effects of the former two parameters are well documented,
      the influence of redox potential on catalytic rates of digestive enzymes is not
      well understood. In this study, we manipulated the midgut redox potential of a
      generalist caterpillar (the corn earworm, Helicoverpa zea) by augmenting
      artificial diet with dithiothreitol, a powerful thiol reducing agent that lowers
      the redox potential in the lumen by 40-45 mV. Effects on total proteolytic
      activity, as well as on elastase, chymotrypsin, trypsin, leucine aminopeptidase,
      and carboxypeptidase A and B activities were measured using azocasein and
      nitroanilide model substrates. The profiles of proteinase activities in the
      epithelium and lumen were also monitored on days 1, 2, and 3 after the molt in
      penultimate instar larvae. Although the reducing agent strongly inhibited the
      activity of some proteinases in vitro, ingestion of the reducing diet failed to
      affect in vivo proteinase activities. There was also no effect on larval relative
      growth, consumption, or digestive efficiencies. We conclude that dietary reducing
      agents must lower midgut redox potential to below -40 mV to significantly impact
      digestive efficiency. Arch.

PMID- 10918309
TI  - Comparative ability to detoxify alder leaf litter in field larval mosquito
      collections.
AB  - The larvicidal effects of polyphenols from dietary alder leaf litter were
      investigated in different field collections of three detritivorous Aedes taxa
      (Ae. detritus, Ae. cataphylla, Ae. rusticus) and compared to the cytochrome P450
      monooxygenase, glutathione S-transferase, and esterase activities. Larvae from
      polyphenol-rich habitats had a higher tolerance for polyphenols and higher midgut
      cytochrome P450 and esterase activities than larvae from polyphenol-poor
      habitats. Furthermore, the role of P450 enzymes in the mechanism of resistance to
      alder polyphenols was suggested by the synergistic effect in vivo of piperonyl
      butoxide in the resistant Ae. rusticus. This confirms the importance of
      polyphenols to larval mosquito performance, and provides evidence for the
      importance of specific detoxification mechanisms for tolerance to dietary
      polyphenols. Arch.

PMID- 10918312
TI  - Ecdysteroid and free amino acid content of eggs of the Colorado potato beetle,
      Leptinotarsa decemlineata.
AB  - In order to identify components of the Colorado potato beetle (CPB) egg that may
      be required by Edovum puttleri, a parasitic wasp that parasitizes the CPB egg, to
      complete development, ecdysteroid and free amino acid content of CPB eggs were
      analyzed by reversed phase high pressure liquid chromatography followed by
      radioimmunoassay to identify ecdysteroids. Ecdysteroid titers were relatively low
      (<300 pg/egg) through day 2 post-oviposition and then increased sharply, reaching
      concentrations >2,500 pg/egg on day 3 post-oviposition. Ecdysone (E), 20
      hydroxyecdysone (20E), and polar conjugates of E were prominent ecdysteroids
      present in eggs sampled on days 0 and 1 post-ecdysis, and E, 20E, three peaks
      containing more polar ecdysteroids (metabolic inactivation products), and polar
      conjugates of E were present in eggs sampled on day 2. Thus, at a time when
      parasitization of CPB eggs by E. puttleri is relatively high (0-48 h),
      physiologically-active ecdysteroids (20E and perhaps E are physiologically
      active) are present at concentrations between 50 and 200 pg/egg. Ecdysone and 20E
      reached their highest levels in day-3 eggs, indicating that ecdysteroid may
      direct physiological processes associated with the completion of CPB embryonic
      development. In day-4 eggs, the concentration of E and 20E fall dramatically and
      polar metabolites of E and/or 20E are now responsible for the high ecdysteroid
      content of the eggs. Interestingly, conjugates of E decrease to relatively low
      levels in day-3 eggs and are absent in day-4 eggs. Therefore, it is likely that
      the increase in E in day-3 eggs is due, in part, to the breakdown of polar
      conjugates of E. Nine amino acids were present in significant quantities in eggs
      sampled at various times between 0 and 48 h post-oviposition. These include
      histidine, glutamine, proline, asparagine, serine, glutamic acid, threonine,
      lysine, and tyrosine. The first three amino acids were present at concentrations
      that were approximately 2 to 6 times greater than the concentrations of the last
      six amino acids. Amounts of most of the free amino acids varied with the age of
      the eggs from which the extract was prepared, but in general, there was no
      correlation between the levels at times of maximum parasitization (0 and 30 h)
      and the levels at the less favored times of parasitization (16 and 48 h). This
      information should facilitate the development of diets for both parasites and
      predators of pest species of beetles. Arch. Insect Biochem. Physiol. 44:172-182,
      2000. Published 2000 Wiley-Liss, Inc.

PMID- 10918311
TI  - Proteolytic activation of canatoxin, a plant toxic protein, by insect cathepsin
      like enzymes.
AB  - Canatoxin is a protein isolated from jackbean (Canavalia ensiformis), seeds.
      Injected intraperitoneally, the toxin is lethal to mice but it is inactive if
      given orally. Canatoxin is also lethal when fed to insects with cathepsin-based
      digestion while insects with trypsin-based digestion are not affected. The
      hypothesis that canatoxin is proteolytically activated by cathepsins was
      investigated. Experiments were performed with 4(th) instar and adult Rhodnius
      prolixus fed meals containing canatoxin (2.5 microg/mg weight body). While 100%
      of nymphs died, no effect was observed in adults. Hemolymph taken from nymphs and
      adults showed the presence of canatoxin's proteolytic fragments. Reduced
      lethality was seen in R. prolixus 4(th) instars fed meals containing canatoxin
      and inhibitors of cathepsin enzymes, E-64 (2.0 microM) or Pepstatin-A (2. 0
      microM). In another approach, canatoxin was digested in vitro with enzymes from
      the bruchid, Callosobruchus maculatus, and the resulting peptides were tested in
      R. prolixus. Three groups of toxic peptides (8,000-12,000 kD range) were
      separated by gel-filtration. When these peptides were fed to the insects
      simultaneously with the cathepsin inhibitors, no protective effect was seen.
      These results confirm the proteolytic activation of canatoxin by insect cathepsin
      like enzymes to produce entomotoxic peptide(s). Furthermore, our data point
      towards overlooked differences in the digestive physiology of distinct life
      stages of R. prolixus. Arch.

PMID- 10918313
TI  - Imaging blood flow in brain tumors using arterial spin labeling.
AB  - Measurements of tumor blood flow (TBF) are important for understanding tumor
      physiology and can be valuable in selecting and evaluating therapies. Brain
      tumors typically present reduced blood flows compared to normal brain tissue.
      This study shows that the arterial spin labeling (ASL) technique can be used to
      measure TBF non-invasively in a rat glioma model. Results show that TBF in the
      core (36.3 +/- 18.9 ml/100g/min, n=4) and peripheral regions (85.3 +/- 26.9
      ml/100g/min, n=4) of the tumor are significantly reduced and show considerable
      heterogeneity compared to cerebral blood flow (CBF) of normal brain tissue (147.7
      +/- 31.1 ml/100g/min, n=4), while T(1) in the tumor (2.6 +/- 0.1 sec) is
      significantly elevated compared to normal tissue T(1) (2.0 +/- 0.0 sec). These
      results strongly support the feasibility of using the ASL technique to evaluate
      different cancer treatment strategies, to monitor the effects of agents designed
      to modulate TBF and oxygenation (e.g., carbogen gas), and to assess and guide the
      use of anti-angiogenic agents. Magn Reson Med 44:169-173, 2000.

PMID- 10918315
TI  - Initial measurements of ifosfamide and cyclophosphamide in patients using (31)P
      MRS: pulse-and-acquire, decoupling, and polarization transfer.
AB  - Ifosfamide and cyclophosphamide are (31)P-containing alkylating agents used
      widely in the treatment of cancer. In this communication it is demonstrated that
      signals from these agents may be detected in the livers of patients undergoing
      treatment using (31)P MRS at 1.5 T. In vitro, signals are enhanced 4-fold by use
      of (1)H-decoupling, with a B(1) field of 100 Hz at -150 Hz relative to water.
      Polarization transfer (BINEPT) enhances signals in vitro by a further factor of
      5.5. Preliminary results using the double-resonance methods in vivo show that the
      technique is practicable although enhancements may be less than observed in
      vitro. Factors affecting signal enhancement in vivo are evaluated. Magn Reson Med
      44:180-184, 2000.

PMID- 10918314
TI  - MR imaging of diffusion of (3)He gas in healthy and diseased lungs.
AB  - Hyperpolarized (3)He gas MRI was used to form maps of the effective diffusivity
      of gas in human lungs. Images of diffusion as well as spin density are presented
      from a study of 11 healthy volunteers and 5 patients with severe emphysema. The
      effective rate of diffusion, D(e), of the gas is reduced by the alveolar walls;
      tissue destruction in emphysema is hypothesized to result in larger D(e). Indeed,
      the mean value of D(e) in the emphysematous lungs is found here to be about 2.5
      times that of healthy lungs, although still smaller than the unrestricted
      diffusivity of (3)He in free air. Histograms of D(e) values across coronal slices
      are presented. The results are discussed in terms of spatial variations,
      variations among individuals, healthy and diseased, and variations due to changes
      in lung volume. Magn Reson Med 44:174-179, 2000.

PMID- 10918316
TI  - Comparison of the quantification precision of human short echo time (1)H
      spectroscopy at 1.5 and 4.0 Tesla.
AB  - Precise quantification of human in vivo short echo time (1)H spectra remains
      problematic at clinical field strengths due to broad peak linewidths and low
      signal-to-noise ratio (SNR). In this study, multiple STEAM spectra (TE = 20 ms,
      volume = 8 cm(3)) were acquired in a single individual at 1.5 T and 4 T to
      compare quantification precision. Test-retest STEAM spectra (volume = 1.5 cm(3))
      were also acquired from the anterior cingulate and thalamus of 10 individuals at
      4.0 T. Metabolite levels were quantified using automated software that
      incorporated field strength-specific prior knowledge. With the distinct methods
      of data acquisition, processing, and fitting used in this study, peak height SNR
      increased approximately 80% while peak linewidth increased by approximately 50%
      in the 8 cm(3) volumes at 4.0 T compared to 1.5 T, resulting in an average
      increase in quantification precision of 39%. Metabolite levels from test-retest
      data (1.5 cm(3) voxels at 4.0 T) were quantified with similar inter- and
      intraindividual variability. Magn Reson Med 44:185-192, 2000. Published 2000
      Wiley-Liss, Inc.

PMID- 10918317
TI  - Effects of ischemia on intracellular rubidium in pig and rat hearts: (87)Rb NMR
      imaging and spectroscopic study.
AB  - 87Rb MR imaging and spectroscopy were used to study the effects of ischemia on
      the properties of K(+) in cardiac tissue. Isolated pig and rat hearts perfused by
      the Langendorff method with Krebs-Henseleit buffer were preloaded with Rb(+).
      Ischemia (Isc) was induced by 120-min occlusion of the left anterior descending
      artery in the pig hearts or by stopping perfusion for 33 min in the rat hearts.
      Serial (87)Rb MR images or spectra from the anterior (An) LV wall of pig hearts
      were acquired continuously. The intensities of the Rb images of the An and
      posterior (Pos) walls were similar and stable during the first 45 min of
      ischemia. The intensity of signal from the An wall (Isc) then gradually increased
      by 60 +/- 8% relative to the preischemic value (vs. 31 +/- 5% increase in Pos
      wall) and necrosis (19 +/- 5% of the LV wall mass) developed upon reperfusion.
      The Rb(+) content was lower in the ischemic (An) than in the normal (Pos) area
      (22.3 +/- 3 vs. 28.4 +/- 1.3 mmol/g wet wt). A similar pattern was observed in
      the peak heights of (87)Rb spectra from the An wall, which increased by 40 +/-
      16% (vs. 21 +/- 11% in control) due to a 12% decrease in the apparent Rb
      linewidth (LW) and a 24 +/- 14% increase in the peak area. The Rb peak comprised
      narrow (297 +/- 21 Hz) and broad (1098 +/- 40 Hz, 59 +/- 3% of total area)
      Lorentzian components. The LW of the broad component decreased by 14%, while the
      narrow component did not change markedly. In the rat hearts ischemia caused a 33
      +/- 4% increase in the (87)Rb peak height as a result of peak narrowing (13 +/-
      1%), and an increase in peak area (17 +/- 5%). The decreases in LW and increases
      in Rb(+) visibility can be explained by an increase in Rb(+) mobility caused by
      displacement of Rb(+) from anionic binding sites by H(+) (ischemic acidosis) and
      changes in intracellular compartmentalization of Rb(+). Magn Reson Med 44:193
      200, 2000.

PMID- 10918318
TI  - High-resolution (1)H and (1)H-(13)C magic angle spinning NMR spectroscopy of rat
      liver.
AB  - High-resolution magic angle spinning (MAS) (1)H NMR spectra of small samples (ca.
      8 mg) of intact rat liver are reported for the first time. One dimensional
      spectra reveal a number of large well-resolved NMR signals mainly from low to
      medium molecular weight compounds (generally <1000 Daltons) from a variety of
      chemical classes. A range of 2D MAS-NMR experiments were performed, including
      (1)H J-resolved (JRES), (1)H-(1)H total correlation spectroscopy (TOCSY) and (1)H
      (13)C heteronuclear multiple quantum coherence (HMQC) to enable detailed signal
      assignment. Resonances were assigned from alpha- and beta-glucose, glycerol,
      alanine, glutamate, glycine, dimethylglycine, lysine, and threonine, together
      with phosphocholine, choline, lactate, trimethylamine-N-oxide (TMAO), and certain
      fatty acids. Well-resolved (1)H NMR signals from glycogen (poly 1-4 alpha
      glucose) were observed directly in intact liver using MAS-NMR spectroscopy. In
      addition, the resonances from the glycogen C(1)H proton in alpha(1-->4) linked
      glucose units with either alpha(1-->4) units adjacent or alpha(1-->6) linked
      branches could be resolved in a high-resolution (1)H NMR experiment giving direct
      in situ information on the ratio of alpha(1-->4) to alpha(1-->6) units. This
      indicates that despite the relatively high MW (>1,000,000 Daltons) there is
      considerable segmental motion in the glycogen molecules giving long (1)H T(2)
      relaxation times. Magn Reson Med 44:201-207, 2000.

PMID- 10918319
TI  - Metabolite and water apparent diffusion coefficients in the isolated rat heart:
      effects of ischemia.
AB  - A decrease in the apparent diffusion coefficient (ADC) of water is important in
      the detection of acute brain disorders, yet it is unknown whether changes in
      myocardial ADCs hold similar potential. Consequently, in this study a STEAM pulse
      sequence was modified in order to measure the ADCs of water and the (1)H-NMR
      detectable metabolites, taurine (an inert marker) and creatine, during perfusion,
      ischemia, and reperfusion in the isolated rat heart. At the short diffusion time
      of 50 ms, myocardial ADCs were (1.06 +/- 0. 07) x 10(-3) mm(2)/s for water, (0.29
      +/- 0.01) x 10(-3) mm(2)/s for taurine and (0.26 +/- 0.01) x 10(-3) mm(2)/s for
      creatine. Heart water and taurine ADCs remained constant during ischemia, yet the
      total creatine ADC increased by 35% owing to the hydrolysis of PCr to creatine.
      The average cardiomyocyte diameter, calculated from taurine ADC values measured
      at diffusion times between 50 ms and 1510 ms, was 40 microm in the perfused heart
      and 27 microm by the end of ischemia. It is concluded that the taurine ADC
      measured at short diffusion times does not reveal ischemic injury in the heart,
      but at long diffusion times may be used to calculate changes in myocyte diameter.
      Magn Reson Med 44:208-214, 2000.

PMID- 10918320
TI  - Analysis of phospholipid molecular species in brain by (31)P NMR spectroscopy.
AB  - Techniques are described for the (31)P NMR analysis of glycerophospholipid (PL)
      headgroup and molecular species in brain. The (31)P NMR spectrum of PLs from
      human temporal cortex, solubilized in aqueous Na cholate, typically showed 3
      major resonances, assigned to phosphatidylcholine (PC) molecular species
      containing 0, 1, or 2 fully saturated acyl chains. Less species resolution was
      obtained for the other PL headgroups under these conditions. Alkylacyl- and
      alkenylacyl-PC were readily discerned using the CHCl(3)-CH(3)OH-H(2)O solvent
      method. The chain-length, temperature, and species dependences of the (31)P NMR
      chemical shifts were explored in model PLs. Assignments of signals from
      phosphatidylethanolamine (PE) subclasses were confirmed in the sodium-cholate
      system by lipase-mediated selective hydrolysis of bovine-brain PE. The utility of
      (31)P NMR to monitor enzymatic PL oxidation was further demonstrated. Possible
      changes in PL composition with postmortem interval (PMI) in rat brain were
      examined. No significant changes were seen in PL headgroup or PC species
      composition with PMI at up to 18 hours. Where comparable, the Na-cholate
      solubilization and solvent methods gave similar quantitative results for
      headgroup analysis on the same samples. The present work demonstrates the
      feasibility and utility of the dual system for analysis of PLs in brain. Magn
      Reson Med 44:215-223, 2000.

PMID- 10918321
TI  - MR imaging of microvasculature.
AB  - An imaging technique is proposed in which the contrast is correlated to the
      morphology of capillaries and other small blood vessels. The technique is based
      on measurements of the relaxation rates 1/T(2) and 1/T*(2) before and after the
      injection of a contrast agent. An image is then formed by mapping the quantity Q
      identical with delta R(2)/(delta R*(2))(2/3), where delta R(2) and delta R*(2)
      are the changes in the relaxation rates due to the contrast agent. If the
      contrast agent concentration is sufficiently high, it is shown that Q is given
      approximately by a simple analytic formula that involves only intrinsic
      properties of the vascular network and the rate of diffusion. In particular, Q is
      sensitive to the histologic vessel density. Theoretical predictions for Q are
      shown to be consistent with experimental data obtained with a rat glioma model
      and normal cerebral cortex. The imaging technique may be useful in characterizing
      tumor angiogenesis. Magn Reson Med 44:224-230, 2000.

PMID- 10918322
TI  - Spatiotemporal dynamics of the BOLD fMRI signals: toward mapping submillimeter
      cortical columns using the early negative response.
AB  - The existence of the early-negative blood-oxygenation-level-dependent (BOLD)
      response is controversial and its practical utility for mapping brain functions
      with columnar spatial specificity remains questionable. To address these issues,
      gradient-echo BOLD fMRI studies were performed at 4.7 T and 9.4 T using the well
      established orientation column model in the cat visual cortex. A robust transient
      early-negative BOLD response was consistently observed in anesthetized cat (-0.35
      +/- 0.09%, mean +/- SD, n = 8 at 2.9 +/- 0.5 sec poststimulus onset for 4.7 T, TE
      = 31 ms; -0.29 +/- 0.10%, n = 4 at 3.0 +/- 0.8 sec poststimulus onset for 9.4 T,
      TE = 12 ms). In addition to its temporal evolution, the BOLD response also
      evolved dynamically in the spatial domain. The initially spatially localized
      early-negative signal appeared to dynamically drain from the active sites toward
      large vessels, followed by a wave of the delayed positive signal, which exhibited
      similar spatiotemporal dynamics. Only the early-negative BOLD response within 2
      sec of the stimulus onset (not the entire dip) yielded columnar layouts without
      differential subtraction. The functional maps of two orthogonal orientations
      using the first 2-sec dip were indeed complementary. On the other hand, the
      delayed positive BOLD response appeared diffused and extended beyond the active
      sites. It was thus less suitable to resolve columnar layouts. These results have
      implications for the design and interpretation of the BOLD fMRI at columnar
      resolution. Magn Reson Med 44:231-242, 2000.

PMID- 10918323
TI  - Tailored SMASH image reconstructions for robust in vivo parallel MR imaging.
AB  - The simultaneous acquisition of spatial harmonics (SMASH) imaging technique uses
      spatial information from an array of RF coils to substitute for omitted encoding
      gradient steps and thereby to accelerate MR image acquisition. Since SMASH image
      reconstructions rely on the accurate generation of sinusoidally varying composite
      sensitivity functions to emulate the spatial modulations produced by gradients,
      the technique was originally believed to be limited to certain image planes or
      coil array configurations which were particularly suited to the generation of
      spatial harmonics. Several key improvements to the SMASH reconstruction procedure
      are described, taking advantage of various degrees of freedom in the spatial
      harmonic fit. The use of tailored fitting procedures, in combination with a
      numerical conditioning approach based on new observations about noise propagation
      in the fit, are shown to allow high-quality SMASH image reconstructions in
      oblique and double-oblique image planes, both in phantoms and in high-resolution
      cardiac MR images. Magn Reson Med 44:243-251, 2000.

PMID- 10918324
TI  - High resolution magnetic resonance angiography non-invasively reveals mouse
      strain differences in the cerebrovascular anatomy in vivo.
AB  - High resolution magnetic resonance angiography (MRA) revealed highly variable
      arterial cerebrovascular structures in mice from different strains and within the
      same strain. C57Black/6 mice presented small unilateral anastomoses between the
      posterior cerebral and the superior cerebellar arteries. Well developed, either
      unilateral or bilateral, posterior communicating arteries (PcomA) were detected
      on CBA mice. The arterial structure of CD1 mice ranged from no detectable
      anastomoses to well developed, unilateral PcomAs. SV-129 mice showed
      significantly shorter middle cerebral arteries compared to the other strains, and
      clear bilateral anastomoses between the posterior cerebral and the superior
      cerebellar arteries. Because of its non-invasiveness, MRA may be of importance in
      murine stroke studies by enabling the selection of animals and/or the side for
      performing the surgical intervention, and the verification of its success. Magn
      Reson Med 44:252-258, 2000.

PMID- 10918325
TI  - Age-related decline in brain white matter anisotropy measured with spatially
      corrected echo-planar diffusion tensor imaging.
AB  - Echo planar (EP) diffusion tensor imaging (DTI) permits in vivo identification of
      the orientation and coherence of brain white matter tracts but suffers from field
      inhomogeneity-induced geometric distortion. To reduce spatial distortion,
      polynomial warping corrections were applied and the effects tested on measures of
      fractional anisotropy (FA) in the genu and splenium of corpus callosum.
      Implementation entailed spatially warping EP images obtained without diffusion
      weighting (b = 0) to long-echo T(2)-weighted fast spin echo images, collected for
      anatomical delineation, tissue segmentation, and coregistration with the
      diffusion images. Using the optimal warping procedure (third-order polynomial),
      the effects of age on FA and a quantitative measure of intervoxel coherence (C)
      in the genu, splenium, centrum semiovale, and frontal and parietal pericallosal
      white matter were examined in 31 healthy men (23-76 years). FA declined
      significantly with age in all regions except the splenium, whereas intervoxel
      coherence positively correlated with age in the genu. Magn Reson Med 44:259-268,
      2000.

PMID- 10918326
TI  - Reduced slab boundary artifact in multi-slab 3D fast spin-echo imaging.
AB  - The three-dimensional multi-slab fast spin-echo (3DFSE) sequence is a time
      efficient technique for volume scanning which provides images with a good signal
      to-noise ratio, adjustable contrast weighting, and high spatial resolution.
      Unfortunately, it suffers from slice-to-slice amplitude variation associated with
      imperfect slab definition. This slab boundary artifact becomes especially
      apparent when multiplanner reformatting is used to create alternate anatomical
      views. The shifted interleaved multi-volume acquisition (SIMVA) described here
      suppresses slab boundary artifact in image space. It displaces each slab (RF
      excitation) position incrementally along the slice (z) axis, in coordination with
      the primary phase encode step, so that the slab boundary artifact is converted
      into a correctable amplitude modulation in the primary phase encode direction
      (k(Y)-axis). After the Fourier transform in primary phase encoding, the slab
      boundary artifact is mapped into a different and less severe artifact on a
      different spatial axis. Preliminary measurements show that SIMVA reduces the slab
      boundary artifact by an order of magnitude in multiplanar reformatted views. Magn
      Reson Med 44:269-276, 2000.

PMID- 10918327
TI  - Recording of the event-related potentials during functional MRI at 3.0 Tesla
      field strength.
AB  - The feasibility of recording event-related potentials (ERP) during functional MRI
      (fMRI) scanning was studied. Using an alternating checkerboard stimulus in a
      blocked presentation, visually evoked potentials were obtained with their
      expected configuration and latencies. A clustered echoplanar imaging protocol was
      applied to observe the hemodynamic response due to the visual stimulus
      interleaved with measuring ERPs. Influences of the electrode/amplifier set up on
      MRI scanning and the scanning process on the recording of electrophysiological
      signals are reported and discussed. Artifacts overlaid on the
      electrophysiological recordings were corrected by post hoc filtering methods
      presented here. Implications and limitations of conducting combined ERP/fMRI
      experiments using higher-level cognitive stimuli are discussed. Magn Reson Med
      44:277-282, 2000.

PMID- 10918328
TI  - A geometric analysis of diffusion tensor measurements of the human brain.
AB  - The degree of diffusion tensor anisotropy is often associated with the
      organization of structural tissues such as white matter. Numerous measures of
      diffusion anisotropy have been proposed, which could lead to confusion in
      interpreting and comparing results from different studies. In this study, a new
      method for representing the diffusion tensor shape, called the three-phase (3P)
      plot, is described. This is a graphical technique based upon a barycentric
      coordinate system, which weights the tensor shape by a combination of linear,
      cylindrical, and spherical shape factors. This coordinate system can be used to
      map and potentially segment different tissues based upon the tensor shape. In
      addition, the 3P plot can be used to examine the shape properties of existing
      measures of diffusion anisotropy. In this paper, the 3P plot is used to compare
      four well-known anisotropy measures: the anisotropy index, the fractional
      anisotropy, the relative anisotropy, and the volume fraction. Computer
      simulations and diffusion tensor images of normal brains were obtained to study
      the properties of this new mapping technique. Magn Reson Med 44:283-291, 2000.

PMID- 10918329
TI  - Multi-component apparent diffusion coefficients in human brain: relationship to
      spin-lattice relaxation.
AB  - In vivo measurements of the human brain tissue water signal decay with b-factor
      over an extended b-factor range up to 6,000 s/mm(2) reveal a nonmonoexponential
      decay behavior for both gray and white matter. Biexponential parametrization of
      the decay curves from cortical gray (CG) and white matter voxels from the
      internal capsule (IC) of healthy adult volunteers describes the decay process and
      serves to differentiate between these two tissues. Inversion recovery experiments
      performed in conjunction with the extended b-factor signal decay measurements are
      used to make separate measurements of the spin-lattice relaxation times of the
      fast and slow apparent diffusion coefficient (ADC) components. Differences
      between the spin-lattice relaxation times of the fast and slow ADC components
      were not statistically significant in either the CG or IC voxels. It is possible
      that the two ADC components observed from the extended b-factor measurements
      arise from two distinct water compartments with different intrinsic diffusion
      coefficients. If so, then the relaxation results are consistent with two
      possibilities. Either the spin-lattice relaxation times within the compartments
      are similar or the rate of water exchange between compartments is "fast" enough
      to ensure volume averaged T(1) relaxation yet "slow" enough to allow for the
      observation of biexponential ADC decay curves over an extended b-factor range.
      Magn Reson Med 44:292-300, 2000.

PMID- 10918330
TI  - Sensitivity profiles from an array of coils for encoding and reconstruction in
      parallel (SPACE RIP).
AB  - A new parallel imaging technique was implemented which can result in reduced
      image acquisition times in MRI. MR data is acquired in parallel using an array of
      receiver coils and then reconstructed simultaneously with multiple processors.
      The method requires the initial estimation of the 2D sensitivity profile of each
      coil used in the receiver array. These sensitivity profiles are then used to
      partially encode the images of interest. A fraction of the total number of k
      space lines is consequently acquired and used in a parallel reconstruction
      scheme, allowing for a substantial reduction in scanning and display times. This
      technique is in the family of parallel acquisition schemes such as simultaneous
      acquisition of spatial harmonics (SMASH) and sensitivity encoding (SENSE). It
      extends the use of the SMASH method to allow the placement of the receiver coil
      array around the object of interest, enabling imaging of any plane within the
      volume of interest. In addition, this technique permits the arbitrary choice of
      the set of k-space lines used in the reconstruction and lends itself to parallel
      reconstruction, hence allowing for real-time rendering. Simulated results with a
      16-fold increase in temporal resolution are shown, as are experimental results
      with a 4-fold increase in temporal resolution. Magn Reson Med 44:301-308, 2000.

PMID- 10918331
TI  - Contrast-enhanced MRI for the assessment of myocardial viability after permanent
      coronary artery occlusion.
AB  - Previous studies in a model of ischemia/reperfusion using a constant infusion of
      Gd-DTPA have shown that distribution volume (lambda) is increased in infarcted
      myocardial tissue. This study examined this technique in the setting of permanent
      coronary artery occlusion. Ten beagles underwent permanent occlusion of a
      coronary artery for 2 days (N = 3), 1 week (N = 4), or 3 weeks (N = 3). Imaging
      was performed at 2 days and, depending on the length of occlusion, 1 week, 2
      weeks, and 3 weeks to follow changes in lambda in vivo. At sacrifice, (201)Tl was
      injected and the extent of the hyperenhanced region was compared to pathology.
      lambda was increased in infarcted tissue by 2 days post occlusion and this
      increase persisted for 3 weeks. At sacrifice, lambda correlated strongly with
      (201)Tl uptake (r = -0.86 to -0.95, P < 0.05; i.e., lambda increased in infarcted
      tissue) and the size of the hyperenhanced region was comparable to pathological
      infarct size (slope 1.006, r = 0.96, P < 0.0001). Thus, beyond 2 days after
      coronary occlusion, MRI, during a constant infusion of Gd-DTPA, can assess
      myocardial viability regardless of the success of reperfusion. Magn Reson Med
      44:309-316, 2000.

PMID- 10918332
TI  - Facilitation of electric forepaw stimulation-induced somatosensory activation in
      rats by additional acoustic stimulation: an fMRI investigation.
AB  - The influence of scanner acoustic noise on somatosensory activation pattern in
      rat cortex was investigated by functional magnetic resonance imaging (fMRI) using
      the blood oxygenation level-dependent (BOLD) contrast. This was achieved by two
      approaches. The first approach was to compare a conventional, loud fMRI sequence
      with a new sequence, in which the noise level was reduced by about 30 dB. In the
      second approach, the inner ear of the animal was destroyed, resulting in
      deafness. We compared the activation patterns obtained with both sequences before
      and after cochleotomy. The activated area was larger when data were sampled with
      background noise, and was also larger before cochleotomy than after. Thus,
      facilitation of somatosensory activation is induced by additional acoustic
      stimulation. Magn Reson Med 44:317-321, 2000.

PMID- 10918333
TI  - 3D interleaved water and fat image acquisition with chemical-shift correction.
AB  - A new technique, 3D interleaved water and fat image acquisition with chemical
      shift correction (3-DIWFAC), was developed to acquire 3D water and fat images in
      a single acquisition time and to combine the water and fat images to produce
      chemical-shift-free images. A 3D gradient-recalled-echo (GRE) sequence was
      implemented with a 1-3-3-1 binomial Shinnar-Le Roux spatial-spectral excitation,
      and with interleaved phase-encoding lines that alternate between water and fat
      excitations separated by half TR. Water-only and fat-only images were then
      realigned to remove chemical shift artifacts. Results from phantoms and human
      subjects demonstrated that the image contrast was the same as in the regular GRE
      sequence. With the chemical shift corrected, the shadow artifacts often seen at
      water and fat boundaries were removed. Since this sequence simultaneously
      provides water-only images showing cartilage and bone lesions, and water-fat
      images that depict soft tissue anatomy, it may be clinically useful in
      musculoskeletal imaging. Magn Reson Med 44:322-330, 2000.

PMID- 10918334
TI  - In vivo, in utero microscopic magnetic resonance imaging: application in a rat
      model of diaphragmatic hernia.
AB  - This article presents a microscopic MR technique for imaging small mammalian
      fetuses in utero and in vivo which can be used as a tool for studying normal and
      abnormal development in small animal fetal models, for targeting in utero
      intervention in such models, and for following development serially. This new
      method is applied to a rat model of congenital diaphragmatic hernia (CDH).
      Pregnant Sprague-Dawley rats were fed nitrofen at 9.5 days postcoitus to induce
      CDH in the fetuses. The dams were imaged to identify fetuses with CDH for
      targeted in utero intervention, which consisted of fetal tracheal ligation.
      Following tracheal ligation, the fetuses were followed serially with our MR
      technique. For MR imaging, the dam was anesthetized with intramuscular ketamine
      and intraperitoneal pentobarbital. In utero imaging was performed on a 4 Tesla
      MRI system using a multislice, fast spin echo sequence with a long TR and short
      effective TE. These results were validated by examining individual fetuses
      postmortem using high-resolution MR and anatomic dissection. The in utero, in
      vivo MR technique is highly accurate for diagnosing CDH and following the effects
      of surgical intervention, and shows promise as a tool for the study of
      embryogenesis in small animal models. Magn Reson Med 44:331-335, 2000.

PMID- 10918336
TI  - Alcohol problems in old age: a review of recent epidemiological research.
AB  - The subject of alcoholism in late life has received relatively little attention
      in the literature. This is despite the fact that elderly people are particularly
      vulnerable to the adverse effects of alcohol. Demographic data predicts that in
      the first half of the next century there will be an increase in the absolute
      number of elderly people with alcohol problems. The recognition and treatment of
      alcohol problems are likely therefore to become more important as this population
      expands. High rates of comorbidity with physical and psychiatric illness mean
      that elderly alcoholics are liable to be frequent users of health facilities.
      Concern has been expressed regarding the impact this trend will have upon health
      services, particularly the high costs of treatment and institutionalization.
      Previous researchers in this field have been disadvantaged by a lack of
      standardized diagnostic criteria and the absence of age-validated screening
      tools. This paper reviews recent publications relating to the epidemiology of
      alcohol problems in the elderly and focuses on comparing the prevalence rates of
      alcohol problems in various clinical settings. Epidemiological research is
      important as it improves the understanding of the scope and impact of a disease
      as well as being a vital component during the planning stage for new services.
      This review highlights some ongoing limitations in recent research.

PMID- 10918335
TI  - On the cause of increased aliasing in the slice-select direction in 3D contrast
      enhanced magnetic resonance angiography.
AB  - The combination of short repetition times and large flip angles typically used in
      3D contrast-enhanced magnetic resonance angiography (3D CE MRA) can significantly
      alter the expected shape of the slab profile for unenhanced tissues, which can
      cause increased aliasing in the slice select direction. In this work, this
      increased slice select aliasing is demonstrated and explained from both
      theoretical and experimental points of view. The effect is due to the Ernst angle
      of unenhanced background tissue occurring on the falling edges of the flip angle
      profile that has been set for the significantly reduced T(1) of contrast-enhanced
      blood. The deleterious aliasing effects are magnified substantially when the
      chosen volume is placed close to surface coil reception with the slice select
      direction perpendicular to the coil axis. Magn Reson Med 44:336-338, 2000.

PMID- 10918337
TI  - Assaultive behaviour in psychiatrically hospitalized elderly: a response to
      psychosocial stimulation and changes in pharmacotherapy.
AB  - The objective of this naturalistic, non-experimental study was to observe and
      evaluate the relationship between psychosocial stimulation and changes in
      medications, and the emergence of the assaultive behaviour, as well as its 24-h
      course, in a psychogeriatric ward. The assaultive behaviour in 29 patients (mean
      age 73.9 years) was rated daily for three consecutive months. Major psychosocial
      stimuli and the number of medication changes were also recorded. More patients
      with organic brain syndromes than with non-organic conditions were aggressive.
      Those with organic syndromes were more likely to become aggressive within any 24
      h period and their aggression was less likely to disappear. The rate with which
      aggression emerged changed following changes in psychotropic medications. The
      presence of psychosocial stimulation and changes in non-psychotropic medications
      modified the rate of disappearance of the aggression. In a psychogeriatric
      inpatient population, both prevalence and incidence of aggression, as well as its
      response to modifying factors, depends critically on pathogenesis. The emergence
      and disappearance of aggression are modified by different factors.

PMID- 10918338
TI  - Characteristics and outcomes of dementia residents in an assisted living
      facility.
AB  - BACKGROUND: Assisted living (AL) is the fastest growing segment of residential
      long-term care in the US. At least half of the estimated 1 million AL residents
      have dementia or cognitive impairment, with many AL facilities offering
      specialized dementia services. Little research has been done on the demographics,
      outcomes, or clinical variables of this population. METHODS: Participants were a
      cohort of 144 residents admitted to the AL unit of Copper Ridge, a specialized
      dementia-care facility. Comparison samples included 737 patients with dementia
      residing in other locations (home, nursing home, and other assisted living
      facilities). Selected measures of cognition, behavior, medical health, and
      function were taken at admission to AL and at 6-month intervals. RESULTS: When
      compared with residents of the dementia-specialized AL facility, dementia
      patients at home were younger, less cognitively impaired, and less likely to
      exhibit wandering, delusions, or aggression. Residents of a dementia-specialized
      nursing home had more cognitive impairment, greater medical comorbidity, and were
      more dependent on caregivers. The 2-year mortality rate in the dementia
      specialized AL was 23%, significantly lower than rates reported for nursing
      homes. Primarily due to increasing care needs, most residents in the specialized
      AL relocated to a nursing home after a median stay of 10.9 months. Depression,
      falling, and wandering were significant predictors of the transition. CONCLUSION:
      Dementia-specialized AL facilities occupy a unique position in the long-term care
      continuum that is distinct from home-care and nursing home facilities. This
      research is the first step toward understanding the significant dementia
      population residing in assisted living.

PMID- 10918339
TI  - Determinants of satisfaction with care and emotional distress among informal
      carers of demented and non-demented elderly patients.
AB  - Little research has been carried out into determinants of both carer satisfaction
      in the caregiving role and how these compare with determinants of emotional
      distress among carers. Principal informal caregivers to 91 patients with
      dementing or non-dementing disorders were identified from consecutive referrals
      to community psychiatric nurses in an old age psychiatry service. Clinical,
      demographic, service and carer satisfaction variables were recorded. Emotional
      distress in carers was measured with the 28 item General Health Questionnaire.
      Dissatisfaction with caregiving was weakly correlated with emotional distress
      (r=0.21, p=0.042). Multiple linear regression revealed two variables which were
      associated with greater dissatisfaction with the caregiving role, the carers'
      overall rating of the degree of difficulty in the caregiving role (p<0.001) and
      younger age of the carer (p=0.014). Emotional distress was independently
      associated with the degree of difficulty in the caregiving situation (p<0.001)
      and inversely with the dependency of the patient on the care (p=0.038). The
      caregiver's assessment of the difficulty in caregiving was associated with both
      carer dissatisfaction and emotional distress in the caregiving role. While
      emotional distress was associated with the perception that the patient could do
      more for themselves, carer dissatisfaction was associated with younger age of the
      carer. There were competing demands on younger carers, particularly work.

PMID- 10918340
TI  - Oestrogens and Alzheimer's disease.
AB  - In the last decade, several reports suggest that oestrogen replacement therapy
      (ORT=ERT=estrogen replacement therapy) might prevent or delay Alzheimer's
      disease. Oestrogens influence and modulate brain structure and brain function.
      There are substantial arguments that the postmenopausal oestrogen loss might,
      together with other factors, accelerate the appearance of Alzheimer's disease.
      The evidence is suggestive, but not compelling, that ORT can reduce the relative
      risk to suffer from Alzheimer's disease. Furthermore, recent findings are
      consistent with the hypothesis that oestrogens might ameliorate the
      symptomatology in early stages of Alzheimer's disease. However, it has to be
      remembered that in most clinical trials the number of oestrogen users was quite
      small, and, usually, oestrogen use was not randomised. The aim of the present
      review is to discuss the data available today in view of their clinical
      relevance.

PMID- 10918341
TI  - How do general practitioners select antidepressants for depressed elderly people?
AB  - This study aimed to identify factors predicting general practitioner's (GPs)
      choice of which antidepressant to prescribe for depression in the elderly, using
      a postal questionnaire survey based on three clinical case vignettes. The main
      outcome measure was the GP's primary reason for selection of an antidepressant.
      GPs prescribing SSRIs gave 'few side effects' and 'safer in overdose' as the most
      important reasons for choosing the antidepressant. Older GPs were more likely to
      use unmodified tricyclics, and selected drugs based on their knowledge and
      experience in use of the drug. Cost was rarely a primary consideration.
      Educational programmes should address the reluctance by some GPs to use new or
      unfamiliar medications and highlight issues relating to side-effects and drug
      safety.

PMID- 10918342
TI  - Contrast sensitivity and visual acuity in patients with Alzheimer's disease.
AB  - Alzheimer's disease is a disorder which is typified by a deterioration in
      cognition and a range of behavioural problems which result in a loss of
      functional ability and often necessitate transfer to residential care. This
      article looks at a growing body of research which is revealing the presence of
      changes in vision, particularly contrast sensitivity and acuity. We discuss the
      possible pathological basis for such deficits, and examine the possibility that
      such changes in vision may impact on the behavioural and functional outcomes of
      the demented individual.

PMID- 10918343
TI  - Cognitive function in UK community-dwelling African Caribbean and white elders: a
      pilot study.
AB  - In recent years there has been interest in risk of cognitive impairment and
      dementia in populations of African origin. Little is known about this risk in
      older African Caribbean residents in the UK. One difficulty is lack of consensus
      over an adequate cognitive test battery for this community. Forty-five African
      Caribbean and 45 age and gender matched white community residents were recruited
      by household enumeration of an inner London electoral ward. These participants
      were administered the MMSE during a screening interview. Where possible, this was
      followed up by tests from the CERAD and CAMCOG neuropsychological batteries, a
      medical examination, and a structured interview with an informant. Based on these
      data, a psychiatrist blind to ethnicity independently rated 86 of these
      participants (41 of the African Caribbeans, all 45 of the whites) as cognitively
      normal, cognitively impaired, or demented. Of 41 African Caribbeans, 18 (44%)
      were rated as cognitively normal, 9 (22%) were rated as cognitively impaired, and
      14 (34%) were rated as demented. Of the 45 whites, 39 (87%) were rated as
      cognitively normal, 4 (9%) were rated as cognitively impaired, and 2 (4%) were
      rated as demented. African Caribbeans scored significantly lower than whites in
      most cognitive test scores, which was not accounted for by their lower
      educational and occupational attainment, or their higher frequency of
      cardiovascular risk factors. African Caribbean elders in the UK appear to be at
      high risk of cognitive impairment and dementia. However, the influence of
      potential confounding factors such as socio-economic position and ill-health, and
      the effect of cultural test bias, cannot be ruled out.

PMID- 10918344
TI  - Has familial aggregation in Alzheimer's disease been overestimated?
AB  - Studies of the familial aggregation of Alzheimer's disease have primarily used
      samples ascertained from tertiary care clinics which may not be representative of
      many AD patients, for example those residing at geriatric nursing homes. Survival
      analysis was used to investigate whether estimates of familial aggregation of AD
      based on a clinic-based AD proband (C-AD) sample (probands: N=544; first degree
      relatives; N=4267) differ from one ascertained at a nursing home (NH-AD;
      probands: N=225; first degree relatives; N=1772). The cumulative survival from AD
      was significantly worse in relatives of the C-AD probands and the overall
      relative risk (RR) of AD in this group was greater than twice that of relatives
      of the NH-AD probands. However, age at onset in C-AD probands was significantly
      earlier than in the NH-AD group and in both groups this factor was negatively
      associated with familial aggregation. When, for this reason, the proband samples
      were matched one-to-one by age at onset, dropping those probands with no match,
      the two curves were close to identical and the RR for the C-AD group of relatives
      was 1.0 The results suggest that estimates of familial risk of AD based on C-AD
      samples are not applicable and overestimate the extent of increased risk for
      relatives of more prevalent, later onset AD probands. However, the overestimate
      can be explained by the typically earlier age at onset in C-AD samples as opposed
      to a sampling bias related to the proband's family history status per se. The
      relationship between onset age and familial aggregation suggests that no single
      estimate of the age-dependent risk (survival curve) is uniformly appropriate for
      relatives of AD probands.

PMID- 10918345
TI  - Comparison of a clock drawing test in elderly schizophrenia and Alzheimer's
      disease patients: a preliminary study.
AB  - The objective of this study was to compare between the quantitative and
      qualitative aspects of a clock drawing test in elderly schizophrenic and
      Alzheimer's disease (AD) patients. Three independent raters performed a
      retrospective analysis of the clock drawing item from the Cambridge Cognitive
      Examination (CAMCOG), in long-term open wards of a public psychiatric hospital
      and an outpatient psychogeriatric clinic. The study group comprised 21 elderly
      schizophrenic patients ('graduates') and 21 AD patients matched for gender and
      education, and cognitive impairment confirmed by a Folstein mini-mental state
      examination (MMSE) score of 18-23. The Clock Drawing Interpretation Scale (CDIS)
      was the measure used. Schizophrenic patients were significantly younger than AD
      patients (63.5 versus 81.3 years, p<0.0001), however, similar concerning gender,
      education, MMSE and CAMCOG scores. CDIS scores were not correlated with age in
      eight group. Inter-rater reliability was high (range 0.84-0.97). No significant
      differences between patient groups were found in mean CDIS total scores. A CDIS
      specific item analysis revealed that schizophrenic patients were significantly
      less impaired than AD patients on three out of 20 items: Number 7 (most symbols
      are aligned in a clockwise or a rightward direction). Number 8 (all symbols are
      totally within a closure figure), and Number 13 (numbers do not go beyond 12).
      Although schizophrenic patients and AD patients had similar total scores on the
      clock drawing test, they differed on specific test items related to
      spatial/planning deficit and preservation.

PMID- 10918346
TI  - The validity of the Hamilton and Montgomery-Asberg depression rating scales as
      screening and diagnostic tools for depression in Parkinson's disease.
AB  - The concurrent validity of the Hamilton Rating Scale for Depression (HAMD-17) and
      the Montgomery-Asberg Depression Rating Scale (MADRS) against the DSM-IV
      diagnosis 'depressive disorder' was assessed in patients with Parkinson's disease
      (PD). Sixty-three non-demented Parkinson's Disease (PD) patients who attended the
      outpatient department of an academic hospital were diagnosed according to a
      standardised research protocol. This protocol consisted of the Schedules for
      Clinical Assessment in Neuropsychiatry (SCAN) to establish the presence or
      absence of 'depressive disorder' according to the DSM-IV criteria, as well as the
      HAMD-17 and the MADRS. Receiver Operating Characteristics curves (ROC curves)
      were obtained and the positive and negative predictive values (PPV, NPV) were
      calculated for different cut-off scores. Maximum discrimination between depressed
      and non-depressed patients was reached at a cut-off score of 13/14 for the HAMD
      17, and at 14/15 for the MADRS. At lower cut-offs, like 11/12 for the HAMD-17 and
      14/15 for the MADRS, the high sensitivity and NPV make these scales good
      screening instruments. At higher cut-offs, such as 16/17 for the HAMD-17 and
      17/18 for the MADRS, the high specificity and PPV make these instruments good
      diagnostic instruments. The diagnostics performance of the HAMD-17 is slightly
      better than that of the MADRS. This study shows that it is justified to use the
      HAMD-17 and the MADRS to measure depressive symptoms in both non-depressed and
      depressed PD patients, to diagnose depressive disorder in PD, and to dichotomize
      patient samples into depressed and non-depressed groups.

PMID- 10918347
TI  - Getting the questions right: an example of loss of validity during transfer of a
      brief screening approach for depression in the elderly.
AB  - Screening for depression in the elderly has been advocated to improve detection
      and management. This article summarises the trend towards briefer screening
      instruments, and the integration of mental health screening with other
      assessments. The study aimed to validate a single question depression screen
      which has previously shown adequate sensitivity and specificity in a new context:
      a multi-faceted assessment instrument used by nurse practitioners within a
      community sample of over 75 year olds. The GMS-AGECAT computerised interview
      assessment was used as a 'gold standard' to determine the accuracy of the
      depression question in this new setting. Three hundred and twenty-eight patients
      were screened by their own nurse practitioners, of whom 100 consenting patients
      underwent a further interview with a research assistant using the GMS-AGECAT. The
      prevalence of depression was 30%, the sensitivity of the question was 67%, and
      its specificity 60% (compared with 88% and 71% previously). Responses indicating
      disability and loneliness were more closely correlated with depression than the
      depression screen itself. Relevant factors may include: the derivation of the
      question, the effect of a different sample, altered reliability when used by
      multiple interviewers, differing patient expectations, and the wording and
      context of the question within the multi-faceted screening instrument. Depression
      screening questions need repeated validation when used in different contexts.
      Patient and staff expectations may influence how screening instruments are used
      in practice in a way that may also alter reliability. Further studies are needed
      to establish the causes of loss of validity when screening approaches are used in
      new settings.

PMID- 10918348
TI  - The sensitivity to change over time of the Bristol Activities of Daily Living
      Scale in Alzheimer's disease.
AB  - Activities of daily living scales can be a useful tool in assessing change in
      people with dementia, either as the disease progresses or in response to
      treatment. However, little data exist as to the sensitivity to change of
      instruments used. The Bristol Activities of Daily Living Scale was developed with
      assistance from the carers of community dwelling people with dementia to be
      completed by such people and has been shown to have internal consistency as well
      as face and construct validity. This study aimed to analyse the sensitivity to
      change of the Bristol Activities of Daily Living Scale in people with Alzheimer's
      disease receiving anticholinesterase medication. Using the Clinician's Global
      Rating of Change as a gold standard for change, differences between Bristol
      Activities of Daily Living Scale scores before and after medication were compared
      with change in Mini-Mental State Examination, Alzheimer's Disease Assessment
      Scale - Cognitive and the Nurses Observation Scale for Geriatric Patients, in 61
      older adults receiving anticholinesterase medication for Alzheimer's disease.
      Both the Bristol Activities of Daily Living Scale and the Nurses Observation
      Scale for Geriatric Patients are sensitive and specific in predicting improvement
      or stability as measured by the clinician's global rating of change. However,
      unlike the Nurses Observation Scale for Geriatric Patients, change over time in
      the Bristol Activities of Daily Living Scale significantly correlates with change
      in the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale
      - Cognitive. The Bristol Activities of Daily Living Scale is sensitive to change
      in activities of daily living and shows the expected and desirable relationship
      with measures of cognition.

PMID- 10918349
TI  - Hindi Mental State Examination (HMSE) as a screening test for illiterate demented
      patients.

PMID- 10918350
TI  - The limitations of current measurement tools for behavioural problems in patients
      suffering from dementia.

PMID- 10918351
TI  - A. Collins, J. Anderson, 'SIADH induced by two atypical Antipsychotics'.
      International journal of geriatric psychiatry 15(3) 2000, 282-283
AB  - The original article to which this Erratum refers was published in the
      International Journal of Geratric Psychiatry 15(3) 2000, 282-283.

PMID- 10918352
TI  - Current awareness in geriatric psychiatry.

PMID- 10918353
TI  - Tris(2,3-dibromopropyl)phosphate causes a gradient of mutations in the cortex and
      outer and inner medullas of the kidney of lacI transgenic rats.
AB  - Tris(2,3-dibromopropyl)phosphate (TDBP) is a kidney carcinogen in rats in which
      exposure results in tumors specifically in the outer medulla. We have previously
      shown that TDBP induces mutation in the rat kidney. Here we demonstrate that TDBP
      induces mutation in the kidney of the F344 Big Blue lacI transgenic rat in a
      gradient with the highest induction (6.4-fold) in the cortex and lowest induction
      (2.2-fold) in the inner medulla, when given at 2000 ppm in the feed for 45 days.
      Similar results were obtained at 100 ppm, although the gradient effect was less
      pronounced. Because exposure to TDBP results in increased cell proliferation in
      the outer medulla, our results suggest that tissue-specific targeting of TDBP
      induced kidney tumors reflects the combination of cell proliferation and mutation
      induction. This is also the first known case when transgenic animals have been
      used to study mutation at the suborgan level.

PMID- 10918354
TI  - DNA degradation by the mixture of copper and catechol is caused by DNA-copper
      hydroperoxo complexes, probably DNA-Cu(I)OOH.
AB  - Free hydroxyl radicals (free (.)OH), singlet oxygen ((1)O(2)), or (. )OH produced
      by DNA-copper-hydroperoxo complexes are possible DNA-damaging reactive oxygen
      species (ROS) in the reaction system containing copper, catechol, and DNA. para
      Chlorobenzoic acid (pCBA) degradation studies revealed that CuCl(2) mixed with
      catechol produced free (.)OH. In the presence of DNA, however, inhibition of the
      pCBA degradation suggested that another ROS is responsible for the DNA
      degradation. Of a series of ROS scavengers investigated, only KI, NaN(3), and Na
      formate-all of the salts tested-strongly inhibited the DNA degradation,
      suggesting that the ionic strength rather than the reactivity of the individual
      scavengers could be responsible for the observed inhibition. The ionic strength
      effect was confirmed by increasing the concentration of phosphate buffer, which
      is a poor (.)OH scavenger, and was interpreted as the result of destabilization
      of DNA-copper-hydroperoxo complexes. Piperidine-labile site patterns in DNA
      degraded by copper and catechol showed that the mixture of Cu(II) and catechol
      degrades DNA via the intermediate formation of a DNA-copper-hydroperoxo complex.
      Replacement of guanine by 7-deazaguanine did not retard the DNA degradation,
      suggesting that the DNA-copper-hydroperoxo complexes do not bind to the guanine N
      7 as proposed in the literature.

PMID- 10918355
TI  - Genetic toxicity evaluation of octamethylcyclotetrasiloxane.
AB  - Octamethylcyclotetrasiloxane (OMCTS; CAS No. 556-67-2) was evaluated in a genetic
      toxicity battery. In preincubation tests with Salmonella typhimurium strains
      TA98, TA100, TA1535, TA1537, and TA1538, no mutagenicity was detected (maximum
      dose = 5 mg/plate) with or without S9 in two independent trials. Treatment of
      cultured Chinese hamster ovary (CHO) cells was limited by cytotoxicity at OMCTS
      concentrations greater than 0.003 mg/mL without S9 and 0.03 mg/mL with S9. CHO
      cells treated with up to 0.003 mg/mL without S9 and 0.03 mg/mL with S9 showed no
      significant dose-related increases in chromosomal aberration frequencies. No
      significant dose-related increases in sister chromatid exchanges (SCEs) occurred
      in OMCTS-treated CHO cells (maximum OMCTS concentration = 0.003 mg/mL without S9;
      0.03 mg/mL with S9). Therefore, OMCTS was concluded to be negative in the SCE
      assay. In a screen for in vivo clastogenic potential, Sprague-Dawley rats
      received 700 ppm OMCTS by whole-body vapor inhalation 6 hr daily for 5 days. A
      negative control group received filtered air on the same schedule. A positive
      control group was exposed to filtered air on the same schedule and received
      cyclophosphamide 24 hr before termination. The OMCTS-treated animals were
      terminated 6 and 24 hr after the final exposure. Positive and negative control
      animals were terminated 24 hr after the last exposure. No significant, treatment
      related increases in chromosomal aberrations were detected. The results of these
      studies indicate that OMCTS does not possess significant in vitro genotoxic
      potential. No adverse genetic findings were seen in the in vivo screen for
      chromosome aberrations.

PMID- 10918356
TI  - Human cytogenetic biomonitoring using flow-cytometric analysis of micronuclei in
      transferrin-positive immature peripheral blood reticulocytes.
AB  - We have developed a method to isolate and analyze nascent human reticulocytes in
      peripheral blood for the presence of micronuclei (MN). For a very short time
      peripheral reticulocytes show residual expression of the transferrin receptor.
      Using immunomagnetic separation of cells expressing the transferrin receptor, a
      population of immature reticulocytes (Trf-Ret) was isolated from peripheral
      blood. In humans, the spleen actively removes micronucleated erythrocytes but
      during the short lifetime of the isolated Trf-Ret only a fraction (less than
      about 20%) of the MN-containing reticulocytes will have been eliminated. Cells
      were stained with the fluorescent dyes Thiazole Orange for RNA and Hoechst 33342
      for DNA and analyzed by flow cytometry and fluorescence microscopy. Baseline
      frequencies of MN-Trf-Ret on a group of healthy donors were found to be 1.1% for
      males and 1.4% for females; however, the gender difference was not significant.
      The frequency of MN-Trf-Ret in the studied group increased with age, and was
      dependent on blood group. In three donors studied over 4 months, the baseline
      level remained stable. In cancer patients treated with radiation or chemotherapy,
      the frequency of MN-Trf-Ret increased 10- to 20-fold after 1-4 days, depending on
      the treatment. A high correlation between flow and manual analysis of MN-Trf-Ret
      was seen. We believe the method has a high potential as a sensitive and rapid
      method for biological monitoring in presumed exposed groups and individuals.

PMID- 10918357
TI  - Diversity of peripheral blood mononuclear cells as revealed by a novel multiple
      microgel "comet assay".
AB  - Multiple microgel comet assay (MMCA) is a metho-dological adaptation of the
      single-cell gel electrophoresis assay in which we have introduced the use of
      standard agarose plug molds in an attempt to improve and expand the applications
      of the assay. We focused on the study of the heterogeneity of peripheral blood
      mononuclear cells (PBMC) at the level of the basal single-strand breakage and the
      DNA damage induction caused by ionizing radiation. Differences among
      subpopulations were also investigated at the level of chromatin organization and
      methylation after NotI digestion of microgel-embedded cells. In parallel
      experiments, the NotI-digested nucleoids were also analyzed with the use of
      pulsed-field gel electrophoresis (PFGE) and the DNA migration patterns were
      compared with the corresponding patterns from the MMCA. Significant heterogeneity
      in the distribution of the oxidative DNA damage, as well as intracellular
      variations in the NotI digestion patterns were observed in the cell population of
      PBMC. The combined use of both the comet assay and PFGE provides a useful model
      for analysis of variation in DNA damage in individual cells as well as
      information on size of DNA fragments.

PMID- 10918358
TI  - Use of the Drosophila wing spot test in the genotoxicity testing of different
      herbicides.
AB  - Four herbicides, namely propanil, maleic hydrazide, glyphosate, and 2,4,5
      trichlorophenoxyacetic acid (2,4,5-T), were investigated for genotoxicity in the
      wing spot test of Drosophila melanogaster. The herbicides were administered by
      chronic feeding to 3-day-old larvae. Two different crosses, a standard (ST) and a
      high-bioactivation (HB) cross, involving the flare-3 (flr(3)) and the multiple
      wing hairs (mwh) markers, were used. The HB cross uses flies characterized by an
      increased cytochrome P-450-dependent bioactivation capacity, which permits a more
      efficient biotransformation of promutagens and procarcinogens. In both crosses,
      the wings of the two types of progeny, which are inversion-free marker
      heterozygotes and balancer heterozygotes, were analyzed. Maleic hydrazide and
      glyphosate proved to be more genotoxic in the ST cross, whereas propanil appeared
      to be slightly more genotoxic in the HB cross. On the other hand, the herbicide
      2,4,5-T increased the mutation frequency for only the small single spots in the
      ST cross.

PMID- 10918359
TI  - Estimation of genome damage after exposure to ionizing radiation and ultrasound
      used in industry.
AB  - The application of ionizing radiation in industry for nondestructive testing
      entails a specific framework of working conditions that include field work,
      facilities with different radioactive sources, maintenance thereof without
      halting production, use of nonionizing radiation, and exposure to chemical
      agents. The present study gives an estimation of recent genome damage in two
      groups of subjects using chromosome aberration assay and micronucleus assay. The
      first group was exposed to (192)Ir and the second was simultaneously exposed to
      (192)Ir and ultrasound. The results show that both groups had higher values of
      chromosome aberrations and micronucleus frequency than controls. The group of
      examinees exposed both to (192)Ir and ultrasound had significantly more chromatid
      breaks, acentric fragments, and dicentric chromosomes, and had a significantly
      higher frequency of micronuclei than subjects exposed to (192)Ir only. The study
      suggests that the detected differences in the genome damage may be attributed to
      the action of ultrasound. This study confirms the dosimetry data for ionizing
      radiation, which indicate that the methods used in industrial radiography and the
      usage of nonionizing radiation entail an increased health risk. In the absence of
      personal dosimeters for nonionizing radiation and chemical agents, biomonitoring
      provides reliable parameters for estimation of genome damage and may lead to
      improvements in working conditions and radiation safety programs.

PMID- 10918360
TI  - Genotoxic activity of five haloacetonitriles: comparative investigations in the
      single cell gel electrophoresis (comet) assay and the ames-fluctuation test.
AB  - Halogenated acetonitriles (HANs) are known to be water disinfectant by-products.
      Their mutagenicity and carcinogenicity have been shown in different test systems
      in vivo and in vitro. They also have clastogenic properties. In this study, the
      ability of HAN to induce single-strand breaks on the DNA of HeLa S3 cells was
      investigated using the single-cell gel electrophoresis (SCGE) assay, which could
      be a good tool with which to evaluate the genotoxicity of chlorinated water. The
      results were compared to those obtained in the Ames fluctuation test using the
      Salmonella typhimurium TA 100 strain without activation. With the Ames
      fluctuation test, a mutagenic effect was observed for chloroacetonitrile (MCAN),
      dichloroacetonitrile (DCAN), and trichloroacetonitrile (TCAN). No mutagenic
      effect was found with bromoacetonitrile (MBAN) or dibromoacetonitrile (DBAN). In
      the SCGE assay, all five HANs induced DNA damage in HeLa S3 cells, increasing the
      mean tail moment significantly. For each compound, a dose-effect relation was
      observed. This study shows that the SCGE assay has greater sensitivity for
      assessing the genotoxicity of HAN than does the Ames-fluctuation test. Brominated
      acetonitriles were more genotoxic than chlorinated acetonitriles in the SCGE
      assay, and the genotoxicity increased with the number of halogenated atoms of the
      compound. This behavior had already been found with other genotoxicity tests.

PMID- 10918361
TI  - Molecular analysis of hprt mutant lymphocytes from 1, 3-butadiene-exposed
      workers.
AB  - 1,3-Butadiene (BD) has been shown to be a potent animal carcinogen and a probable
      human carcinogen, yet the molecular mechanisms of BD genotoxicity and
      carcinogenicity still are not fully understood. Our hypothesis is that
      metabolites of BD induce specific structural changes in the human hprt gene like
      those observed in vitro in TK6 cells and in vivo in the mouse. Characteristic
      mutations in BD-exposed subjects can be identified and used as biomarkers for
      monitoring genotoxic effects associated with BD exposure. Molecular analysis of
      hprt mutant lymphocytes from BD-exposed workers and unexposed control subjects
      was carried out to identify changes in the structure of the hprt gene. A
      multiplex polymerase chain reaction (PCR) assay was used to detect exon deletions
      in 360 hprt mutant clones. We determined that exon deletions were significantly
      more frequent (P < 0.05) in BD-exposed workers (17.5%) than in control subjects
      (9.7%). Sequence analysis of hprt cDNA from 175 independent mutants indicated
      that the distribution of the types of mutations was different between the workers
      and the unexposed control subjects. There was a significant increase in -1
      frameshift mutations in BD-exposed workers, predominantly in repeated DNA
      sequences, and single-base substitutions were decreased to 66% in the workers
      compared to 83% in the control subjects (P < 0.05). In addition to the spectral
      changes, hprt clonal assays revealed an elevation in mutant frequency in the
      lymphocytes of workers (N = 10) when compared with that in unexposed control
      subjects (N = 11; P < 0. 05). There also was a twofold increase of A:T --> T:A
      transversions in BD-exposed workers (16% in BD-exposed workers compared to 8% in
      controls, P = 0.25). Some of the BD-associated changes in mutational spectra
      observed in our study have the potential for application in monitoring genotoxic
      effects related to butadiene exposure.

PMID- 10918362
TI  - Comparison of the results of a modified miniscreen and the standard bacterial
      reverse mutation assays.
AB  - The bacterial reverse mutation assay (Ames test) provides a rapid assessment of
      the mutagenic potential of chemicals. The assay is widely used in the
      pharmaceutical industry for early assessment during candidate compound selection
      and for regulatory drug submissions. Early in development, many candidate
      compounds are available in only very small quantities. The use of the standard
      plate incorporation bacterial reverse mutation assay for screening, using only a
      single petri plate per concentration, requires the use of approximately 140 mg of
      test compound to test up to a stock concentration of 100 mg/ml (5000
      microg/plate) in five strains of bacteria. A modification of the existing Ames
      Miniscreen assay has been developed using six-well cell-culture dishes that
      requires only 21 mg of compound to test a stock concentration of up to 100 mg/ml
      (2000 microg/well) in three strains of bacteria. The standard plate incorporation
      assay and the modified Miniscreen assays conducted on proprietary compounds
      without and with metabolic activation have yielded a high degree of concordance
      in findings.

PMID- 10918363
TI  - A study of the electrospray ionisation of selected coumarin derivatives and their
      subsequent fragmentation using an ion trap mass spectrometer.
AB  - The electrospray ionisation (ESI) of selected coumarin derivatives and their
      subsequent fragmentation using an ion trap mass spectrometer have been
      investigated. Sequential product ion fragmentation experiments (MS(n)) were
      performed in order to elucidate the degradation pathways for these compounds. A
      comparison was also made between these ESI spectra and those obtained under
      electron impact (EI) conditions. The data presented in this paper provides useful
      information on the effect of different substituents on the
      ionisation/fragmentation processes and can be used in the characterisation of
      these compounds.

PMID- 10918364
TI  - Electrophoretic mobility-assisted identification of proteins by nanoelectrospray
      capillary electrophoresis/mass spectrometry under methanolic conditions.
AB  - A novel method for electrophoretic mobility-assisted identifications of proteins,
      using capillary electrophoresis/mass spectrometry (CE/MS) under methanolic
      conditions, was developed. The number of functional groups of the enzymatic
      digest peptides was estimated from a single run CE/MS analysis and utilized as an
      additional tag for database searching in addition to the mass map of the
      peptides. The additional amino acid information thus obtained can improve the
      confidence level of the protein identification. The database searching software
      algorithm ProFound was modified to accept the tag, based on this new concept. In
      this study, optimization of the CE/MS conditions for the estimation of basic
      functional groups was performed as an example. An accurate value of the number of
      such functional groups was obtained from CE characteristics when methanolic
      buffer (methanol/formic acid/water = 60:20:20) was used, via an excellent
      correlation (r = 0.997) between the number of functional groups of the peptides
      and [MW((2/3))]. The mass spectrometry sensitivity was also improved when using
      the methanolic buffer in comparison with that obtained using aqueous 1% formic
      acid buffer. The identification of a protein of Saccharomyces cerevisiae, which
      was separated by two-dimensional electrophoresis, was performed using the
      methanolic buffer in combination with sheathless nanoelectrospray CE/MS. A
      protein spot that had not been identified by MALDI-TOFMS and LC/MS/MS was
      successfully identified using this new method.

PMID- 10918365
TI  - Secondary ion mass spectrometric investigation on ruthenium oxide systems: a
      comparison between poly- and nanocrystalline deposits
AB  - The influence of different RuO(2) crystallite sizes was investigated by secondary
      ion mass spectrometry (SIMS) on the oxide deposited on various support materials
      (Ni, Ti, Al(2)O(3), oxidized Si(100)). In order to examine the effect of an
      oxidic environment on the film structure, RuO(2) 20%-TiO(2) 80% at. mixed oxide
      was deposited on Ti. The polycrystalline coatings were prepared by heating the Ru
      (and Ti)-containing solution dropped on the supports.1 RuO(2) nanocrystalline
      coatings were grown by chemical vapor deposition (CVD) from Ru(COD)(eta(3)
      allyl)(2).2 The identification of mixed oxide clusters showed the higher
      reactivity of Ni and Al(2)O(3) over the other substrates. Diffusion and migration
      characteristics were observed to be influenced by the nature of the support. The
      results are complementary to those of a previous SIMS investigation.3 Copyright
      2000 John Wiley & Sons, Ltd.

PMID- 10918366
TI  - Electrospray tandem mass spectrometry in the rapid identification of alpha-chain
      haemoglobin variants.
AB  - The potential use of electrospray tandem mass spectrometry in the rapid
      characterisation of haemoglobin variants found in the Swedish population has been
      assessed. Analysis times of the order of 5 -10 min were routinely achieved, and
      identification of variants using mass spectrometry as the sole analytical
      technique was possible. However, additional information, readily available from
      isoelectric focusing experiments, made identification simpler and more secure. In
      the present communication we report on the identification of the alpha-chain
      variants, Hb Russ, Hb Le Lamentin and Hb Q-Iran. The identifications were
      confirmed by the use of nucleotide sequencing techniques.

PMID- 10918367
TI  - Metastable decompositions of gem-dialkoxyalkanes upon electron impact. III.
      Diethoxymethane (CH(2)(OCH(2)CH(3))(2))
AB  - Unimolecular metastable decomposition of diethoxymethane (CH(2)(OCH(2)CH(3))(2),
      1) upon electron impact has been investigated by means of mass-analyzed ion
      kinetic energy (MIKE) spectrometry and theD-labeling technique in conjunction
      with thermochemistry. The m/z 103 ion ([M - H](+) : CH(OCH(2)CH(3)) =
      O(+)CH(2)CH(3)) decomposes into the m/z 47 ion (protonated formic acid, CH(OH) =
      O(+)H) by consecutive losses of two C(2)H(4) molecules via an m/z 75 ion. The
      resulting product ion at m/z 47 further decomposes into the m/z 29 and 19 ions by
      losses of H(2)O and CO, respectively, via an 1,3-hydroxyl hydrogen transfer,
      accompanied by small kinetic energy release (KER) values of 1.3 and 18.8 meV,
      respectively. When these two elimination reactions are suppressed by a large
      isotope effect, however, another 1,1-H(2)O elimination with a large KER value
      (518 meV) is revealed. The m/z 89 ion ([M - CH(3)](+) : CH(2)(OCH(2)CH(3))O(+) =
      CH(2)) decomposes into the m/z 59 ion (CH(3)CH(2)O(+) = CH(2)) by losing CH(2)O
      in the metastable time window. The source-generated m/z 59 ion ([M -
      OCH(2)CH(3)](+) : CH(2) = O(+)CH(2)CH(3)) decomposes into the m/z 41 (CH(2) =
      CH(+)CH(2)) and m/z 31 (CH(2) = O(+)H) ions by losses of H(2)O and C(2)H(4),
      respectively, with considerable hydrogen scrambling prior to decomposition.
      Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10918369
TI  - Tandem mass spectrometry of some nitropyridylaryl sulfides
AB  - The electron impact tandem mass spectrometry of 3- and 5-nitropyridinylaryl
      sulfides are reported and discussed. The [M-1](+) ion is observed as the base
      peak for all the 5-nitropyridinylaryl sulfides, series I, whereas the 2-mercapto
      3-nitrosopyridine fragment at m/z 139 represents the base peak for the 3-nitro
      isomers, series II, with the exception of the 3-substituted derivatives and the
      unsubstituted parent sulfide. The proposed fragmentation processes are
      substantiated by tandem mass spectrometry (MS/MS). Hammett correlation analysis
      of the substituent effect on the formation of fragments [RH(4)C(6)S](+),
      [C(6)H(4)R](+) and [M-HNO(2)](+) is discussed. Copyright 2000 John Wiley & Sons,
      Ltd.

PMID- 10918368
TI  - Analysis of urinary nucleosides. I. Optimisation of high performance liquid
      chromatography/electrospray mass spectrometry.
AB  - In order to optimise the analysis of urinary nucleosides by high performance
      liquid chromatography/mass spectrometry (HPLC/MS), the HPLC separation of these
      compounds was performed at different 'flow rates' and 0.2mL/min was found to give
      both a better separation and ionisation. The ionisation conditions were optimised
      to give the best intensity of the molecules quasi-molecular ions. The ion
      distribution profile and ionisation in both positive and negative mode were
      examined and the detection of the protonated molecule in positive mode chosen for
      further analysis. The limits of detection of the method developed are reported
      and representative LC/MS and LC/MS/MS spectra shown. Typical urinary nucleoside
      chromatograms are presented.

PMID- 10918371
TI  - The search for stable gas phase b(1) ions derived from aliphatic amino acids: a
      combined experimental and ab initio study.
AB  - Several previous studies have shown that b(1) ions (formally acylium ions,
      H(2)NCHRCO(+)) derived from protonated aliphatic amino acids are unstable in the
      gas phase, fragmenting via decarbonylation to form a(1) ions (iminium ions, H(2)N
      = CHR(+)). Herein we examine the fragmentation reactions of ten potential b(1)
      ion precursors to determine whether stable aliphatic b(1) ions can be formed in
      the gas phase. Of all the systems studied, only the aziridine b(1) ion and the
      dehydroalanine b(1) ion were found to be stable. These experimental results are
      entirely consistent with ab initio calculations (at the MP2(full)/6-311G** level)
      which indicate that while the loss of CO from the b(1) ion of glycine is
      barrierless and exoethermic, the related losses from the b(1) ions of aziridine
      and dehydroalanine have significant barriers (29.5 and 16.2 kcal mol(-1),
      respectively) and are endothermic overall.

PMID- 10918370
TI  - Determination of terbinafine (Lamisil) in human hair by microbore liquid
      chromatography/tandem mass spectrometry.
AB  - An analytical method for the determination of terbinafine (Lamisil(R)) in human
      hair was developed and validated. Human hair (10 mg) was hydrolyzed in 0.50 mL of
      5.0 N sodium hydroxide for 1.5 h. The aqueous layer was extracted with 1.5 mL of
      n-hexane. The organic layer was separated and re-extracted with 0.20 mL of formic
      acid (12.5%)/2-propanol (85:15, v/v). The aqueous layer was separated and 0.010
      mL of the aqueous extract was injected onto a reversed-phase microbore (50 x 1.0
      mm i.d.) column for analysis by liquid chromatography/tandem mass spectrometry
      (LC/MS/MS). The instrument was equipped with an electrospray ionization (ESI)
      interface and operated in the positive ion mode of detection. Interday and
      intraday accuracy and precision were assessed from the relative recoveries of
      spiked samples analyzed on three different days. The method showed excellent
      specificity and ruggedness with a lower limit of quantitation of 10 ng/g (i.e.,
      10 ppb) using 10 mg of human hair.

PMID- 10918372
TI  - Quantitation of peptides and proteins by matrix-assisted laser
      desorption/ionization mass spectrometry using (18)O-labeled internal standards.
AB  - A method for quantitating proteins and peptides in the low picomole and sub
      picomole range has been developed using matrix-assisted laser
      desorption/ionization mass spectrometry (MALDI-MS) with internal (18)O-labeled
      standards. A simple procedure is proposed to produce such internal standards for
      the tested sample by enzymatic hydrolysis of the same sample (with known
      concentration) in (18)O-water. A mathematical algorithm was developed which uses
      the isotopic patterns of the substance, the internal standard, and the
      substance/internal standard mixture for accurate quantitation of the substance. A
      great advantages of the proposed method is the absence of molecular weight
      limitation for the protein quantitation and the possibility of quantitation
      without previous fractionation of proteins and peptides. Using this strategy, the
      peptide angiotensinogen and two proteins, RNase and its protein inhibitor, were
      quantified by MALDI-time-of-flight (TOF) mass spectrometry.

PMID- 10918373
TI  - A simple sample preparation for enhancing the sensitivity of mass spectrometric
      oligosaccharide determinations through the use of an adsorptive hydrophobic
      resin.
AB  - A simple microadsorption technique is described to remove detergent additives
      from oligosaccharide samples before their mass spectrometric analysis. The
      described methodology has been validated with submicrogram quantities of
      contaminated glycoproteins. This procedure is applicable to investigating minute
      quantities of glycans in both the positive- and negative-ion mode of matrix
      assisted laser desorption/ionization mass spectrometry.

PMID- 10918374
TI  - Matrix-assisted laser desorption/ionization fourier transform ion cyclotron
      resonance mass spectrometry with pulsed in-source collision gas and in-source ion
      accumulation.
AB  - A new matrix-assisted laser desorption/ionization (MALDI) source for Fourier
      transform ion cyclotron resonance mass spectrometry (FTMS) has been developed.
      The new source is equipped with a hexapole ion guide. The sample on the laser
      target is one millimeter from the hexapole ion guide, so that ions are desorbed
      directly into the guide. A device for pulsing collision gas in direct proximity
      to the laser target makes it possible to cool the ions, which have a kinetic
      energy spread of several electron volts when produced by the MALDI process. These
      ions are trapped in the hexapole where positive potentials at the laser target
      and at an extraction plate help trap ions along the longitudinal axis. After a
      pre-defined trapping time the voltage of the extraction plate is reversed and the
      trapped ions are extracted for transmission to the ion cyclotron resonance cell.
      Accumulation of ions from multiple laser shots in the hexapole before mass
      spectrometric analysis increases sensitivity. Preliminary sensitivity studies
      with substance P show that 10 attomoles of analyte applied on the target can be
      detected with a signal-to-noise (S/N) ratio >15.

PMID- 10918375
TI  - Structural analysis of diacyl peroxides by electrospray tandem mass spectrometry
      with ammonium acetate: bond homolysis of peroxide-ammonium and peroxide-proton
      adducts.
AB  - Organic peroxides have significant implications in organic chemistry and
      biological processes. The weak O-O bond makes them extremely difficult to
      characterize by conventional analytical methods. Diacyl peroxides are one of the
      major radical sources in polymerization and organic synthesis. It is well known
      that diacyl peroxides are thermal labile and thus are not amenable to study by
      gas chromatography/mass spectrometry (GC/MS). Electrospray tandem mass
      spectrometry (ESI-MS/MS) has been applied to the structural analysis of diacyl
      peroxides by formation of ammonium adducts. Collision induced dissociation (CID)
      studies of the ammonium adducts of the peroxide [M + NH(4)](+) give collision
      energy dependent fragments. For most diacyl peroxides, homolysis of the peroxy
      bond predominates the fragmentation pathways of the peroxide-ammonium adducts.
      Deuterated substrates have been employed to provide evidence for typical
      fragmentation pathways. The CID studies were also used to locate the O-18 in some
      O-18 specifically labeled diacyl peroxides. For branched alkyl or alkoxy
      substrates, McLafferty rearrangement and decarboxylation become a major pathway.
      By comparison with some anhydride analogues, ESI-MS/MS can also be used to study
      this class of compounds.

PMID- 10918376
TI  - Formation, photodissociation and structure of chromium/phosphorus binary cluster
      ions
AB  - Chromium/phosphorus binary cluster ions, [Cr(n)P(m)](+/-), produced by laser
      (532nm) ablation on a tablet of well-mixed chromium and red phosphorus powder,
      were studied with a home-built tandem time-of-flight (TOF) mass spectrometer. The
      clusters thus formed are mostly rich in phosphorus. There is an odd-even
      oscillation in the intensity of the [CrP(m)](+) series, i.e. the mass peaks of
      even m are higher than those of odd m. The peaks of [CrP(4)](+) and [CrP(8)](+)
      are especially prominent, which may be ascribed to the specific stability of P(4)
      sub-structures. There are also some intense peaks in the spectrum assigned to
      [Cr(3)P(8)](+), [Cr(4)P(9)](+), [Cr(5)P(11)](+), [Cr(6)P(12)](+), [Cr(8)P(14)](+)
      clusters, etc., which have stable compositions. The stability of these species is
      consistent with a simple qualitative electronic structure model, in which the
      valence electrons of P are filled into the d orbitals of Cr. The
      photodissociation of some cluster ions was also studied. DFT calculations were
      performed on three small cluster ions to provide some insight into their
      structures. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10918377
TI  - Mass spectrometry of avermectins: structural determination of two new derivatives
      of Ivermectin B(1a).
AB  - Fragmentation pathways of Avermectins were studied by electron impact (EI),
      chemical ionisation (CI), electrospray ionisation (ESI) and by collision
      experiments. Structure characterisation was obtained using ESI combined with
      multi-stage (MS(n)) tandem mass spectrometry, analysis of homologues, and effects
      on fragment masses of H/D exchange. By these approaches the structures of two new
      derivatives of Avermectins were characterised.

PMID- 10918378
TI  - On-line nitrate-delta(15)N extracted from groundwater determined by continuous
      flow elemental analyzer/isotope ratio mass spectrometry.
AB  - Nitrate-delta(15)N from groundwater samples is determined on an inorganic nitrate
      derivative using automated, continuous-flow elemental analyzer/isotope ratio mass
      spectrometry (EA/IRMS). Nitrate is extracted and concentrated based on a recently
      published ion-exchange resin method. Freeze-dried AgNO(3) (0.5-1.5 mg) is packed
      in silver-foil cups and combusted within the reactor of an NC2500 elemental
      analyzer (CE Instruments, Milan, Italy) using its existing reaction scheme for
      nitrogen and carbon analysis. delta(15)N is determined using a Finnigan MAT
      DELTA(plus) isotope ratio mass spectrometer (Bremen, Germany). Results are drift
      corrected to a AgNO(3) working standard that has been calibrated against known
      AgNO(3). Despite high concentrations of carbonate, the precision for all runs is
      better than 0.10 per thousand. The combination of this extraction procedure with
      commercially available delta(15)N analysis instrumentation offers a precise on
      line alternative to existing methods, with considerable reduction in labor and
      analysis time.

PMID- 10918379
TI  - A free-flow electrophoresis chip device for interfacing capillary isoelectric
      focusing on-line with electrospray mass spectrometry.
AB  - When electrospray ionisation mass spectrometry (ESI-MS) is used on-line with
      capillary isoelectric focusing (CIEF), the presence of the carrier ampholytes
      creating the IEF pH gradient is not desirable. With the purpose of removing these
      ampholytes, we have developed a free-flow electrophoresis (FFE) device and
      coupled it to CIEF. The different parameters inherent to the resulting CIEF/FFE
      system were optimised using ultraviolet absorbance (UV) detection. The on-line
      coupling of this system with ESI-MS was successfully realised for three model
      proteins (myoglobin, carbonic anhydrase I and beta-lactoglobulin B).

PMID- 10918380
TI  - Mass spectral fragmentations of cholesterol acetate oxidation products.
AB  - In this work, electron-impact mass spectroscopy (EI-MS) was employed on a wide
      range of sterol compounds in order to study their behaviour with regard to their
      functional groups. In particular, some specific mechanisms of fragmentation
      occurring in these substrates (i.e. retro-Diels-Alder reaction, neutral molecules
      eliminations, specific hydrogen migrations) were investigated. Loss of the alkyl
      side chain and of the D ring were observed in all cases. Finally, a
      classification of sterols on the basis of characteristic mass spectral fragments
      is suggested, and further applications to substrates with functional groups on
      positions other than the A and B rings is proposed.

PMID- 10918381
TI  - Rapid identification of saponins in plant extracts by electrospray ionization
      multi-stage tandem mass spectrometry and liquid chromatography/tandem mass
      spectrometry.
AB  - Electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) and
      liquid chromatography coupled with on-line mass spectrometry (LC/MS/MS) were
      applied to characterize saponins in crude extracts from Panax ginseng. The MS(n)
      data of the [M - H](-) ions of saponins can provide structural information on the
      sugar sequences of the saccharide chains and on the sapogins of saponins. By ESI
      MS(n), non-isomeric saponins and isomeric saponins with different aglycones can
      be determined rapidly in plant extracts. LC/MS/MS is a good complementary
      analytical tool for determination of isomeric saponins. These approaches
      constitute powerful analytical tools for rapid screening and structural
      assignment of saponins in plant extracts.

PMID- 10918382
TI  - Identification of proteins from one-dimensional sodium dodecyl sulfate
      polyacrylamide gel electrophoresis using electrospray quadrupole-time-of-flight
      tandem mass spectrometry.
AB  - The potential of electrospray tandem mass spectrometry using a quadrupole-time-of
      flight tandem mass spectrometer was evaluated for the identification of two
      unknown proteins from one-dimensional polyacrylamide gel electrophoresis (1-D
      PAGE). Two proteins from cellular cultures of mammary epithelia were purified by
      1D-PAGE. Their identification was achieved using peptide sequence tags generated
      by LC/Q-TOF-MS/MS, whereas MALDI-TOF mass mapping failed for these proteins
      obtained from simple 1D-PAGE separation.

PMID- 10918383
TI  - Determination and excretion study of gestrinone in human urine by high
      performance liquid chromatography and gas chromatography/mass spectrometry.
AB  - Gestrinone was studied by HPLC for screening and by GC/MS for confirmation. Three
      unknown peaks were found by HPLC which are probably the metabolites of
      gestrinone, and conjugated gestrinone in dosed human urine. The metabolites and
      gestrinone were excreted as the conjugated forms. The total amounts of metabolite
      1 and conjugated gestrinone, recovered after 48 h, were 0.20 and 0.32 mg,
      respectively. When metabolite 1 was tested by LC/MS and LC/MS/MS, the parent ion
      was m/z 327, [MH](+), and fragment ions were seen at m/z 309 [MH - H(2)O](+), 291
      [MH - 2H(2)O](+), 283, 263 and 239. The TMS-enol-TMS ether derivative of
      gestrinone has three peaks in the GC/MS chromatogram formed by tautomerism. The
      reproducibility of the derivatization method was stable and recoveries were over
      87% when spiked into blank urine.

PMID- 10918384
TI  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of
      self-assembled monolayers of ruthenium complexes on gold
AB  - Self-assembled monolayers (SAMs) of three ruthenium complexes,
      [Ru(L)(2)](PF(6))(2), [Ru(L)(tpyPO(3))](PF(6))(2), and
      [Ru(L18)(tpyPO(3))](PF(6))(2), were prepared on evaporated gold films on glass or
      stainless steel plates; where L = 2, 6-bis(benzimidazoyl)pyridine, tpyPO(3) = 2,6
      bis(2,2':6', 2"-terpyridyl)pyridine phosphanate, and L18 = 2, 6-bis(N
      octadecylbenzimidazoyl)pyridine. Structures of these SAM complexes were studied
      by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOFMS). The SAMs were either prepared by direct binding of Ru-complexes to
      Au films by alkanethiol or by the multilayer method. In the multilayer method 1,4
      thiobutylphosphate was used to form a base layer on an Au film, and the base
      layer was then chemically bridged to the Ru-complexes by zirconium phosphate.
      MALDI-TOFMS of SAM1, that had been prepared by direct binding of
      [Ru(L)(2)](PF(6))(2) to the Au film by an octanethiol group, showed cleavage at
      the S-Au linkages and elimination of the counter anion to yield a molecular ion
      and its dimeric ion. On the other hand, SAM2 and SAM3, which had been prepared by
      bridging Ru-complexes [Ru(L)(tpyPO(3))](PF(6))(2) or
      [Ru(L18)(tpyPO(3))](PF(6))(2) to the base layers with zirconium phosphate, showed
      dissociation from the base layers and elimination of the counter anion to give
      ions of the Ru complex molecules and their fragmentation ions. No molecular ion
      containing the base layer resulting from the S-Au bond cleavage was observed.
      Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10918385
TI  - Nano-electrospray mass spectrometry with a modified commercial IonSpray source
AB  - Electrospray mass spectrometry is a standard tool for the investigation of
      biological samples. Due to the high flowrates of the standard sources, large
      sample amounts are required and it is almost impossible to spray physiological
      solutions due to their aqueous medium. The introduction of microelectrospray
      sources has made it possible to decrease the sample amounts needed and enabled
      the use of buffered solutions. In this work, a nanoES-like source based on a
      modification of an existing IonSpray source is introduced. In contrast to other
      nanoES sources available, the modification presented allows a fast change between
      the nanoES and the normal IonSpray modes. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10918386
TI  - Electron impact mass spectra of 6-substituted 12H-tetrachlorodibenzo
AB  - Bis(2-hydroxy-3,5-dichlorophenyl)methane and its cyclized derivatives (6
      substituted 12H-tetrachlorodibenzo[d,g] [1,3, 2]dioxaphosphorin-6-oxide and
      sulfides) were analyzed by EI-MS, and the mass spectra are discussed. It was
      shown that the mass spectra of the cyclized derivatives are rather different from
      that of the parent compound. The relative roles of the S and O atoms were very
      important, and led to special ions which could indicate certain moieties within
      the molecular structure. Thus, the fragment ions at m/z 63 and 333 indicate a
      cyclic structure with a (P=S) group, while m/z 397 indicates P(=S)S or P(=S)-Cl)
      moieties, and m/z 380 with high intensity indicates P(=O)O. Copyright 2000 John
      Wiley & Sons, Ltd.

PMID- 10918387
TI  - CGH analysis of radon-induced rat lung tumors indicates similarities with human
      lung cancers.
AB  - Epidemiological studies have shown that inhalation of radon, a radioactive gas,
      is associated with an increased risk for lung cancer. We have developed a model
      of radon-induced rat lung tumors to characterize cytogenetic and molecular events
      involved in radon-induced lung tumorigenesis. Using comparative genomic
      hybridization (CGH), gains and losses of genetic material were investigated in a
      series of 13 carcinomas and four adenomas of the lung. Frequent losses occurred
      at 4q12-21, 5q11-33, and 15q, which are homologous to human chromosome (HSA)
      bands 7q21-36, 1p31-36/9p21-31, and 13q14.1-14.3/3p14.2, respectively. These
      regions are frequently (30-80%) deleted in human lung cancer and contain tumor
      suppressor genes or proto-oncogenes such as MET, CDKN2A/p16/MTS1,
      CDKN2B/p15/MTS2, FHIT, and RB1 or yet to be identified genes. Frequent gains
      involved 6, 7q34-qter, and 19q; chromosomes 6 and 7 being homologous to human
      2p21-25 and 8q21-24 where the MYCN and MYC oncogenes are located. The genetic
      similarities between rat and human lung cancer suggest common underlying
      mechanisms for tumor evolution in both species. Moreover, cytogenetic and
      molecular genetic analyses of radon-induced rat lung tumors could help to better
      understand the development and progression of radon-induced lung cancer in man.

PMID- 10918388
TI  - Isolation of a novel gene on 8p21.3-22 whose expression is reduced significantly
      in human colorectal cancers with liver metastasis.
AB  - Metastasis, a major factor contributing to poor prognosis of cancer patients, is
      caused by a complex series of events that involve many genes. To investigate this
      process, we analyzed by differential display three cell lines that had been
      established from a murine colon adenocarcinoma (colon 26), NL4, NL17, and NL22,
      each of which possessed a different potential for metastasis in mice. We report
      here the identification of a novel gene, ream (reduced expression associated with
      metastasis), which showed significantly lower expression in NL17 and NL22 with a
      high potential for metastasis than in NL4 without a metastatic potential. The
      human counterpart of murine ream expressed two sizes of transcript, 4.4 kb and
      1.8 kb, both encoding the same 367-amino acid peptide, which appeared to contain
      four membrane-spanning regions. The cDNA showed no significant homology to any
      known genes in the public database. Human REAM was found to lie within an 800-kb
      segment of 8p21.3-22, where we had previously identified a commonly deleted
      region in colorectal and hepatocellular carcinomas. Its expression was reduced in
      more than half of the human colorectal cancers we examined, particularly in
      advanced stages with liver metastasis. Furthermore, we identified somatic
      mutations of this gene in a colorectal cancer, a hepatocellular carcinoma, and a
      nonsmall lung cancer among 111 human tumors of various stages examined.

PMID- 10918389
TI  - Mapping of the chromosome 19 q-arm glioma tumor suppressor gene using
      fluorescence in situ hybridization and novel microsatellite markers.
AB  - Allelic loss of chromosome arm 19q is a frequent event in human diffuse glioma,
      suggesting the presence of a tumor suppressor gene. Previous loss of
      heterozygosity (LOH) analyses have mapped this gene to a 1.4-megabase interval,
      between the genetic markers D19S412 and STD. Further narrowing of this interval
      has been limited by the resolution of mapped polymorphic markers. In the present
      study, we have used genomic clones mapped to 19q as fluorescence in situ
      hybridization (FISH) probes to map the breakpoints of 13 gliomas with 19q13.3
      deletion boundaries. In addition, we have developed three new polymorphic
      microsatellite markers (D19S1180, D19S1181, and D19S1182) that map between
      D19S412 and STD and have used these new markers to identify two gliomas with
      small deletions between the D19S412 and STD markers. Collectively, these data
      suggest that the region of common deletion may be as narrow as 150 kb and should
      facilitate future efforts to identify the glioma 19q tumor suppressor gene.

PMID- 10918390
TI  - Bladder cancer genotype stability during clinical progression.
AB  - Genomic instability is manifested by the accumulation of large numbers of
      mutations. The rate at which mutations accumulate has been difficult to estimate
      because serial comparisons are required. For further insight into how quickly
      mutations accumulate during clinical progression, cell lines sequentially
      isolated 6 or 11 months apart from two patients with metastatic bladder cancer
      were compared for loss of heterozygosity (LOH). The genomes were scanned at
      approximately 200 polymorphic microsatellite loci to increase the resolution and
      sensitivity for losses. The cell lines from both patients had evidence of genomic
      instability, with aneuploidy, chromosomal instability, and fractional allelic
      losses of 0.15 and 0. 48, respectively. However, additional changes were
      relatively infrequent, with more than 90% identity between the initial and
      recurrent cell lines. Allelic losses were not randomly scattered, but clustered
      on specific chromosomes. Therefore, the numbers of loci with further LOH during
      the clinical progression of some bladder cancers are small relative to the total
      number of loci with LOH, suggesting that most allelic losses accumulate before
      clinical presentation.

PMID- 10918391
TI  - Somatic frameshift alterations in mononucleotide repeat-containing genes in
      different tumor types from an HNPCC family with germline MSH2 mutation.
AB  - Hereditary nonpolyposis colorectal cancer (HNPCC) is caused by a germline
      mutation in one of several DNA repair genes, which in the tumors is reflected as
      microsatellite instability (MSI). MSI+ tumors have been found to carry somatic
      frameshift mutations in mononucleotide repeats within the coding regions of
      several genes involved in growth control, apoptosis, and DNA repair, e.g.,
      TGFBRII, BAX, IGFIIR, TCF4, MSH3, and MSH6. We have studied the occurrence of
      somatic frameshift alterations in these mononucleotide repeat-containing genes in
      24 tumors (15 colorectal cancers, 1 colon adenoma, 4 endometrial cancers, 1
      ovarian cancer, 1 gastric cancer, 1 urothelial cancer, and 1 duodenal cancer)
      from 14 individuals in an HNPCC family with germline hMSH2 mutation. Such somatic
      frameshift mutations occurred at a variable frequency; the long mononucleotide
      repeats that characterize intronic MSI markers were mutated in the majority of
      tumors, 13 of the tumors displayed alterations in the (A)(10) tract of TGFBII,
      eight tumors (all of gastrointestinal origin) had alterations in the (A)(9)
      repeat of TCF4, and one to five tumors had somatic frameshift alterations in the
      shorter mononucleotide repeats of IGFIIR, BAX, MSH3, and MSH6. Thus, longer
      mononucleotide repeats were more frequently affected by somatic frameshift
      mutations. The pattern of alterations varied between the tumors from different
      family members as well as between different tumors from the same individual. To
      what extent this variable pattern depends on the widespread mismatch repair
      deficiency induced by the underlying MSH2 mutation, or represents alternative
      ways whereby the tumors can achieve a tumorigenic phenotype, is unknown. We
      suggest, however, that the accumulation of somatic frameshifts, rather than the
      specific loci in which these occur, drives the development of the tumorigenic
      phenotype in HNPCC.

PMID- 10918392
TI  - MLL amplification in myeloid leukemias: A study of 14 cases with multiple copies
      of 11q23.
AB  - We here report the clinical, cytogenetic, fluorescence in situ hybridization
      (FISH), and Southern blot data on 14 patients with a myeloid malignancy and
      structural aberration of chromosome band 11q23 associated with overrepresentation
      or amplification of the MLL gene. The number of copies of MLL varied from three
      (two cases) to a cluster consisting of multiple hybridization spots. Together
      with previous reports, available data indicate that amplification of 11q23/MLL is
      a recurrent genetic change in myeloid malignancy. It affects mainly elderly
      patients and is often associated with dysplastic bone marrow changes or with
      complex karyotypic aberrations, suggestive of genotoxic exposure. It is
      associated with a poor prognosis. In addition, FISH analysis of nine cases with
      additional 11q probes showed that the overrepresented chromosomal region is
      generally not restricted to MLL, and Southern blot analysis indicated that
      amplification does not involve a rearranged copy of this gene. The significance
      of MLL amplification and the mechanisms by which it could play a role in
      leukemogenesis and/or disease progression remain to be elucidated.

PMID- 10918394
TI  - Complex germline rearrangement of BRCA1 associated with breast and ovarian
      cancer.
AB  - Germline mutations in BRCA1 predispose to breast and ovarian cancer. Most
      germline BRCA1 mutations are small insertions, deletions, or single base pair
      (bp) substitutions. These mutation classes are rarely found as somatic mutations
      in BRCA1. On the other hand, somatic deletions of multiple mega-base pairs (Mb)
      including BRCA1, as reflected by loss of heterozygosity, occur frequently in both
      inherited and sporadic breast and ovarian cancers. To determine whether deletions
      or rearrangements of hundreds to thousands of bps might contribute to inherited
      mutation in BRCA1, we developed a Long PCR strategy for screening the entire
      genomic BRCA1 locus in high-risk families. We evaluated genomic DNA from one high
      risk family of European ancestry with BRCA1-linked cancer in which no genomic
      mutations had been detected using conventional methods. Long PCR revealed a
      complex mutation, g.12977 ins10 del1039 (based on GenBank L78833), comprising an
      inverted duplication and deletion in BRCA1 that removes portions of exon 3 and
      intron 3, including the 5' splice site for intron 3. As a result of the deletion,
      exon 3 is skipped, leading to a truncated protein and disease predisposition.
      Unlike previously reported large germline deletions in BRCA1, neither breakpoint
      resides within an Alu element. The g.12977 ins10 del1039 mutation was not
      detected among 11 other breast cancer families, nor among 406 breast cancer
      patients unselected for family history.

PMID- 10918393
TI  - The hD52 (TPD52) gene is a candidate target gene for events resulting in
      increased 8q21 copy number in human breast carcinoma.
AB  - Chromosome band 8q21 is frequently overrepresented in human cancer, but to date
      no 8q21 target gene has been proposed. The hD52 (TPD52) gene is of potential
      significance in breast and other cancers due to its location and expression
      pattern. Fine mapping of hD52 placed this locus within the peak of the 8q21
      amplicon delineated in the SK-BR-3 breast carcinoma cell line, and a positive
      association between hD52 gene dosage and transcript levels was subsequently
      demonstrated in four breast carcinoma cell lines, including SK-BR-3. Increased
      copy number (ICN) was measured using Southern blot analyses in 3/32 human breast
      carcinomas at hD52, and the related hD54 gene in 20q13.2-q13.3. Subsequent
      immunohistochemical analysis of hD52 expression in 19 breast carcinomas with
      varying hD52 gene dosages demonstrated a significant positive association between
      hD52 dosage and hD52 expression using a Spearman rank correlation coefficient
      (r(s) = 0.573, alpha = 0.01) and a Wilcoxon rank-sum test (alpha = 0.05). On the
      basis of its map location and expression pattern in breast carcinoma, we
      therefore propose hD52 as a candidate target gene at chromosome band 8q21.

PMID- 10918395
TI  - Decreased expression of the INK4 family of cyclin-dependent kinase inhibitors in
      Wilms tumor.
AB  - Cyclin-dependent kinase (CDK) inhibitors represented by the INK4 family
      (including p16(INK4a, CDKN2A), p15(INK4b, CDKN2B), p18(INK4c, CDKN2C), and
      p19(INK4d, CDKN2D)) are regulators of the cell cycle shown to be aberrant in many
      types of human cancer. We tested the hypothesis that these CDK inhibitors are a
      target for altered gene expression in Wilms tumor. Using RT-PCR, gene expression
      of the INK4 family was found to be decreased in 9 of 38 Wilms tumor samples
      obtained from the National Wilms Tumor Study Group (NWTSG) tissue bank. All the
      affected tumor samples were of favorable histology. Methylation-specific PCR
      revealed that methylation in the p16 promoter region may be responsible for
      altered expression. The incidence of loss of p16 expression may increase with
      increasing tumor stage, i.e., 1/10 (10%) with stage I/II FH Wilms tumor, 2/10
      (20%) with stage III FH Wilms tumor, and 4/10 (40%) with stage IV FH Wilms tumor.
      Thus, determining the expression status of the INK4 family may have potential
      prognostic value in the management of Wilms tumor.

PMID- 10918396
TI  - Chromosomes 1 and 5 harbor plasmacytoma progressor genes in mice.
AB  - Mouse spectral karyotyping (SKY) was employed to analyze 29 primary BALB/c
      plasmacytomas (PCTs) for the presence of chromosomal aberrations that took place
      subsequent to the Myc-activating T(12F1;15D2) or T(6C1;15D2) translocations, the
      initiating oncogenic mutations in plasmacytomagenesis. Recurrent amplifications
      of chromosome (Chr) 1 (48% prevalence) and promiscuous non-reciprocal
      translocations of Chr 5 (52% prevalence) suggested the existence of important PCT
      progressor genes on bands 1B/C and 5F. The additional occurrence of sporadic
      aberrations (93% prevalence) most likely reflected the general instability of the
      PCT genome. This instability, however, was not consistent, as two PCTs lacked
      secondary cytogenetic changes detectable by SKY. Our findings led us to conclude
      that BALB/c PCTs show a remarkably similar degree of cytogenetic heterogeneity to
      human multiple myeloma, despite being genetically defined (inbred mouse strain)
      and uniformly initiated (deregulation of Myc). Published 2000 Wiley-Liss, Inc.

PMID- 10918397
TI  - Genetic aberrations detected by comparative genomic hybridization predict outcome
      in patients with endometrioid carcinoma.
AB  - Endometrial cancer progression is determined by a complex pattern of multiple
      genetic aberrations, but how these aberrations affect prognosis is unknown. In
      this study, we undertook a genome-wide screening to detect genetic changes by
      comparative genomic hybridization (CGH) in 51 tumors from patients with primary
      endometrioid carcinoma of the uterine corpus. The observed genetic changes were
      subsequently correlated with the progression of the disease and the clinical
      outcome in each case. The average number of genetic aberrations (copy number
      gains and losses) was significantly greater in non-surviving patients than in
      disease-free patients (12. 6 vs. 2.7, P < 0.0001). According to multivariate
      analysis, lymph node metastasis (P = 0.015), cervical involvement (P = 0.007) and
      one or more copy number losses at 9q32-q34, 11q23, or Xq12-q24 (P = 0.023) were
      significantly predictive of death from the disease. Interestingly, lymph node
      metastasis was significantly associated with copy number gains at 8q22-q23 and
      8q24-qter (P = 0.003 and P = 0.025, respectively). Moreover, cervical involvement
      was also correlated significantly not only with gains of 8q22-q23 and 8q24-qter
      but also with loss of 11q23 (P = 0.04, 0.0003, and P = 0. 009, respectively).
      These results suggest that analysis of genetic changes may help predict clinical
      outcome and the presence of metastatic disease as well as assist in therapeutic
      decision making for patients with endometrioid carcinoma.

PMID- 10918398
TI  - Chromosomal alterations in human pancreatic endocrine tumors.
AB  - Comparative genomic hybridization (CGH) was used to investigate changes in DNA
      copy numbers in 25 paraffin-embedded samples of pancreatic endocrine tumors from
      23 patients. Insulin was the dominant hormone in 12, glucagon in 7, somatostatin
      in 1, and pancreatic polypeptide in 2 tumors. One to 15 (mean, 8.1) changes in
      DNA copy numbers were observed in 22 of the 25 tumors. The most recurrent
      aberration, found in 68% of the tumors, involved gains in chromosome 7 with a
      minimal overlapping region at 7q11.2. Other frequent gains included chromosomes
      19 (60%) and 14 (56%). Chromosome arm 20q was amplified in 48% of the cases with
      the minimal overlapping region of 20q11.1-13.1. The two most frequent DNA losses
      were found at 11q21-22 in 32% and at 11p13-15 in 24% of the cases. The amplified
      chromosomal regions contain several candidate genes that may be involved in islet
      cell tumorigenesis. The regions with most frequent losses are likely to contain
      still uncharacterized tumor suppressor genes. Wiley-Liss, Inc.

PMID- 10918400
TI  - Immunobiology of allogeneic peripheral blood mononuclear cells mobilized with
      granulocyte-colony stimulating factor.
AB  - The use of mobilized peripheral blood (PB) stem cells for autologous
      transplantation initially generated much enthusiasm because of enhanced
      engraftment in comparison to marrow stem cells and avoidance of general
      anesthesia for the donor. Its application to the allogeneic setting seemed
      inevitable. For obvious ethical reasons, allogeneic donors are mobilized with
      cytokines only, mainly granulocyte colony-stimulating factor (G-CSF). Results
      from preliminary studies suggest that in comparison to standard bone marrow
      transplants, outcomes such as engraftment, host-versus-graft reaction, graft
      versus-host disease, graft-versus-leukemia and immunological reconstitution may
      be different. Surprisingly, G-CSF, previously recognized as a late acting lineage
      specific factor for neutrophil production, not only disrupts homeostasis between
      stem cells and their microenvironment, but also induces significant quantitative
      and qualitative changes in the accessory cell compartment, affecting lymphocytes,
      monocytes, natural killer, dendritic, and stromal cells. Furthermore,
      mobilization of huge numbers of non-professional antigen presenting cells (CD34+
      stem cells) amplifies the tolerizing potential of PB stem cell grafts. Thus, G
      CSF mobilization provides PB transplants with different immunobiologic properties
      in comparison to standard bone marrow grafts. Whether these immunobiologic
      differences will lead to better transplant outcomes remains to be shown through
      much awaited results of large randomized clinical trials.

PMID- 10918401
TI  - Outcome of T cell-depleted transplantation after conditioning with an intensified
      regimen in patients aged 50 years or more is comparable with that in younger
      patients.
AB  - One hundred and thirty-one patients were transplanted for AML-CR1, ALL-CR1 or CML
      CP1 after conditioning with 120 mg/kg body weight cyclophosphamide and 2 x 4.5 Gy
      TBI. Conditioning was intensified with the addition of 42 mg/m2 idarubicin.
      Grafts were T cell-depleted using counterflow centrifugation. Donors were HLA
      identical siblings. We compared outcome of BMT in 109 patients aged less than 50
      (median, 35) years with that of 22 patients with an age of 50 years or more
      (median, 53 years). For the patients aged <50 years, 2-year probabilities of
      treatment-related mortality, relapse, survival and leukemia-free survival were
      26% (95% CI, 17% to 35%), 26% (95% CI, 17% to 35%), 64% (95% CI, 55% to 73%), and
      56% (95% CI, 47% to 65%). For the patients aged > or =50 years, these figures
      were 13% (95% CI, 0% to 30%), 24% (95% CI, 6% to 42%), 66% (95% CI, 46% to 86%),
      and 67% (95% CI, 47% to 87%), respectively. Outcome did not differ significantly
      between the two age groups. TRM was within the range of that reported in the
      literature for recipients of T cell-depleted grafts. We conclude that T cell
      depleted transplantation after a conditioning regimen that was intensified with
      the addition of idarubicin is feasible in patients aged > or =50 years. For this
      age group of patients, results of nonmyeloablative regimens should be compared
      with that obtained with T cell-depleted grafts.

PMID- 10918403
TI  - Outcome of unrelated bone marrow donor searches in 174 children resulting in 45
      patients transplanted in the HLA-matched and -mismatched situation.
AB  - The aim of the study was to evaluate the outcome of unrelated bone marrow donor
      (UBMD) searches initiated for 174 children between 1986 and 1997. Seven patients
      were registered twice so that a total of 181 UBMD searches took place. At the
      time of registration, patients suffered from hematological malignancies (n =
      121), non-malignant hemopathies (n = 26) and inborn errors (n = 34). Forty-five
      of the patients (26%) were given transplants from unrelated donors of whom 26
      (58%) were HLA-mismatched transplants. Our strategy accepted HLA mismatches at
      the time of donor selection, using Thymoglobuline as part of the conditioning
      regimen. Of the 45 patients given unrelated donor transplants, overall survival
      was 60% at 3 years and concerned 27 patients of whom 14 were from HLA-mismatched
      donors. Disease-free survival for hematological malignancies was 65% in HLA
      matched transplants and 50% in HLA-mismatched transplants. For some patients
      (16%) urgency led us to use alternative options: non-identical related donor (n =
      14), autograft (n = 10), related cord blood transplant (n = 4). For others, UBMD
      searches were stopped because of favorable evolution (n = 29), death (n = 24),
      disease progression (n = 22) or other reasons (n = 21). By the end of the follow
      up period, 88 patients had died (50%), 75 (43%) are currently alive with or
      without being transplanted of whom eight are still having active searches and 11
      are no longer contactable. In conclusion, in severe disease in children, an
      immediate transplant from a partially matched donor might be preferable to a
      prolonged search for a full match. Consequently, this strategy increases the
      number of patients for whom a suitable donor can be found. We have chosen this
      option in order not to delay BMT; in so doing we have obtained encouraging
      results which include high overall survival, low incidence of acute GVHD grade
      III-IV and low percentage of relapse even in mismatched pairs.

PMID- 10918402
TI  - Foscarnet prophylaxis of cytomegalovirus infections in patients undergoing
      allogeneic bone marrow transplantation (BMT): a dose-finding study.
AB  - This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic
      bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or
      T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after
      BMT and continued until day +100. We explored four different dose levels,
      patients being entered at the lowest dose level until one patient experiences CMV
      reactivation, identified as two consecutive positive CMV antigenemias (CMVAg
      emia). The four dose levels expressed as mg/kg/day between days 1 and 30
      (induction) and between days 31 and 100 (maintenance) were respectively: dose
      level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90
      (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN
      > or =0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt
      > or =30x10(9)/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10
      patients at a median interval of 53 days post-BMT (range 33-89) with a median of
      10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg
      emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose
      levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels
      I, II and 0/11 at dose levels III, IV (P = 0. 07). The median number of CMV
      antigen-positive cells at diagnosis of CMV infection was different: 13 in dose
      levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was
      seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of
      discontinuation in nine patients (45%). Renal toxicity was reversible in all nine
      patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose
      levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet
      exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and
      transplant-related mortality with acceptable and reversible renal toxicity.

PMID- 10918404
TI  - Delayed stem cell transplantation for the management of relapsed or refractory
      multiple myeloma.
AB  - The optimal timing of stem cell transplantation for multiple myeloma is
      controversial. Late stem cell collection is undesirable because of the inability
      to mobilize stem cells. We report on 64 recipients of stem cells collected within
      1 year after diagnosis, none of whom had transplantation in plateau phase of
      their disease. Patients seen within 12 months after diagnosis received four
      cycles of standard vincristine, doxorubicin, and dexamethasone (VAD) chemotherapy
      and then had stem cells mobilized. Patients were then placed on maintenance
      vincristine, BCNU, melphalan, cyclophosphamide, and prednisone or melphalan and
      prednisone chemotherapy for 12 cycles. At the sign of first progression,
      transplantation occurred. Fourteen patients were refractory to VAD chemotherapy,
      20 relapsed on maintenance chemotherapy, and 30 relapsed off chemotherapy. The
      time to platelet engraftment was not affected by the duration of stem cell
      cryopreservation or extent of chemotherapy exposure after mobilization. The
      complete response rate was 34%. The actuarial median survival from initial
      diagnosis, from transplant day 0, and post-transplant progression-free survival
      was 51, 20 and 11.4 months, respectively. The patient status at transplantation
      and percentage of plasma cells circulating in the blood at apheresis influenced
      post-transplant survival; circulating plasma cells, status at transplantation and
      plasma cell labeling index influenced progression-free survival. Response
      duration was shorter in patients relapsing on chemotherapy.

PMID- 10918405
TI  - High-dose busulfan, melphalan and thiotepa as consolidation for non-inflammatory
      high-risk breast cancer.
AB  - The purpose of this study was to evaluate the toxicity and efficacy of high-dose
      busulfan, melphalan and thiotepa (Bu/Mel/TT) in patients with high-risk non
      inflammatory breast cancer defined as stage II disease > or =10 lymph nodes (n =
      52) or stage III (n = 69), and prognostic factors for treatment outcome. One
      hundred and twenty-one patients (median age, 46 years) were treated with high
      dose Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) (HDC) followed by
      autologous stem cell infusion (ASCI). One hundred patients were initially treated
      with surgery followed by standard adjuvant chemotherapy prior to HDC/ASCI. Twenty
      one patients with stage III disease had inoperable tumors at diagnosis and were
      treated with neoadjuvant chemotherapy and surgery before HDC/ASCI. Transplant
      related mortality was 6%. The probabilities of event-free survival (EFS) at 3 and
      5 years (median follow-up of 36 months) from transplant were, for all patients:
      0.62-0.60; stage II: 0.71-0.67: stage III: 0.55-0.55 (for stage III adjuvant and
      neoadjuvant groups: 0.60-0.60 and 0.42-0.42, respectively). Multivariate analysis
      did not identify variables associated with poor outcome. The efficacy of
      Bu/Mel/TT is similar to other HDC regimens reported for patients with high-risk
      non-inflammatory breast cancer. Bu/Mel/TT has high activity in stage II disease
      and a moderate benefit in stage III operable tumors.

PMID- 10918406
TI  - High-dose melphalan-based chemotherapy and autologous stem cell transplantation
      after second look laparotomy in patients with chemosensitive advanced ovarian
      carcinoma: long-term results.
AB  - The importance of dose intensity has been suggested in ovarian carcinoma. We
      retrospectively evaluated the long-term results of melphalan-based high-dose
      chemotherapy (HDC) with hematopoietic rescue in a unicentric series of 33
      patients with advanced ovarian cancer sensitive to first-line chemotherapy.
      Before HDC, treatment with debulking surgery and platinum-based chemotherapy was
      followed by second-look operation (SLO). HDC consisted of melphalan (n = 8),
      melphalan and cyclophosphamide (n = 9), or melphalan, etoposide and carboplatinum
      (n = 16). Toxicity was mainly hematological. One death occurred from infection
      during aplasia. With a median follow-up of 60 months after intensification, the 5
      year progression-free survival (PFS) rate was 29% and the 5-year overall survival
      (OS) rate was 45%. Survival differed significantly according to tumor status at
      SLO. Women with microscopic or macroscopic disease at SLO, ie with a pathological
      partial response to first-line therapy (PPR), had survivals of 7% at 5 years,
      similar to other salvage therapies. Better results were obtained in the 20 women
      with a complete pathological response (PCR) at SLO with 43% 5-year PFS (median,
      51 months) and 75% 5-year OS (median not reached). In conclusion, melphalan-based
      HDC with hematopoietic rescue had an acceptable toxicity in patients with
      chemosensitive advanced ovarian cancer. In situations of salvage therapy for
      patients in PPR, this treatment was not effective in long-term analysis. On the
      contrary, long-term results were favorable in patients with PCR, suggesting
      further prospective randomized studies comparing HDC and other consolidation
      treatments should be undertaken in this particular situation.

PMID- 10918407
TI  - CD52 antibodies for prevention of graft-versus-host disease and graft rejection
      following transplantation of allogeneic peripheral blood stem cells.
AB  - Graft-versus-host disease (GVHD) is a major cause of mortality and morbidity
      after allogeneic bone marrow transplantation, but can be avoided by removing T
      lymphocytes from the donor bone marrow. However, T cell depletion increases the
      risk of graft rejection. In this study, two strategies are used to overcome
      rejection: (1) use of high doses of stem cells obtained from peripheral blood
      (PBSC), (2) admixture with a CD52 monoclonal antibody in order to deplete both
      donor and residual recipient lymphocytes. Two antibodies are compared: CAMPATH-1G
      (rat IgG2b) and its humanized equivalent CAMPATH-1H (human IgG1). A total of 187
      consecutive patients at six centers received PBSC transplants from HLA-matched
      siblings between 1997 and 1999. A wide spectrum of diseases, both malignant and
      non-malignant, was included. The recovery of CD34+ cells after antibody treatment
      was close to 100%. The risk of acute GVHD (grade 2 to 4) was 11% in the CAMPATH
      1G group and 4% in the CAMPATH-1H group (P = NS). The risk of chronic GVHD (any
      grade) was 11% in the CAMPATH-1G group and 24% in the CAMPATH-1H group (P = 0.03)
      but the risk of extensive chronic GVHD was only 2%. The overall risk of graft
      failure/rejection was 2%, not significantly different between the two antibodies.
      Antibody treatment was equally effective at concentrations between 10 microg/ml
      and 120 microg/ml and it made no significant difference to the outcome whether
      the patients received post-transplant immunosuppression or not (87% did not).
      Transplant-related mortality in this heterogenous group of patients (including
      high-risk and advanced disease) was 22% at 12 months. It is proposed that
      treatment of peripheral blood stem cells with CAMPATH-1H is a simple and
      effective method for depleting T cells which may be applicable to both autologous
      and allogeneic transplants from related or unrelated donors. Special advantages
      of this approach are the simultaneous depletion of donor B cells (which reduces
      the risk of EBV-associated lymphoproliferative disease) and the concomitant
      infusion of CAMPATH-1H to deplete residual recipient T cells and thus prevent
      graft rejection.

PMID- 10918408
TI  - Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage
      fluids as early detection of acute GVHD following BMT: evidence of a significant
      relationship.
AB  - We evaluated the relationship between CMV and human herpes virus-6 (HHV-6)
      reactivation and the incidence of grades 2 to 4 acute GVHD post BMT.
      Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on
      post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV
      plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades
      2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed
      grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%)
      developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight
      (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13
      patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who
      were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4
      acute GVHD. In all experiments, the difference between the groups was significant
      (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus
      infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of
      moderate to severe acute GVHD.

PMID- 10918409
TI  - Characterization of the T cell receptor repertoire of neonatal T cells by RT-PCR
      and single strand conformation polymorphism analysis.
AB  - We have analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) the
      individual non-germ line configurations of the T cell receptor (TCR) Vbeta chains
      expressed by T cells from eight individual cord blood specimens. cDNA from each
      cord blood was amplified using a common primer coupled with a primer specific for
      each of 22 variable elements of the Vbeta chain family and the amplified
      fragments were separated under high resolution conditions. With cDNA from adult
      blood (as a control), all of the TCR chains were amplified as a smear consistent
      with the extensive polyclonality of adult T cells. In contrast, a heterogeneous
      pattern of amplification was observed with cDNAs from cord blood: only 26.7+/
      21.9% of the 22 Vbeta chains analyzed were amplified as a smear. The majority of
      them were amplified as a discrete number of bands (up to 10) (in 68.2 +/-18.7% of
      samples) and some of them as a single fragment (4.0+/-7.8%). Only one of the
      eight samples analyzed expressed the majority (72.7%) of its Vbeta chains as a
      smear, consistent with an adult-like TCR repertoire. In conclusion, cord blood
      expressed, on average, a less complex TCR repertoire than adult blood.

PMID- 10918410
TI  - In vivo cytokine responses to interleukin-2 immunotherapy after autologous stem
      cell transplantation in children with solid tumors.
AB  - The potent immunostimulatory cytokine interleukin-2 (IL-2) has been extensively
      investigated for its potential to induce anti-tumor immunity in a number of tumor
      models. Only recently the complex interplay of mutually suppressive or supportive
      cytokines of the IL-2-induced network of cytokines has been better characterized.
      The aim of this study was to assess which of these in vitro findings are
      reproducible in vivo in recipients of stem cell transplants (SCT), since in these
      patients long- lasting impairments in cytokine inducibility have been described.
      We have therefore studied the kinetics of putative modulators and mediators of IL
      2-induced immune activation, namely IL-1beta, IL-4, IL-5, IL-10, IL-12, soluble
      Fas ligand (sFasL), and GM-CSF during IL-2 therapy. All patients were children or
      adolescents suffering from solid tumors with poor prognosis who received three 5
      day courses of high-dose intravenous IL-2 as an adjuvant to their radio
      chemotherapy and autologous SCT. While IL-1beta, IL-4 and IL-12 were not, and
      sFasL was only mildly affected by the IL-2 therapy, we observed a consistent and
      early rise of IL-10, IL-5, and GM-CSF. These increases were rapidly reversible
      after discontinuation of IL-2 therapy. The inducibility of IL-10, IL-5 and GM-CSF
      was more pronounced with increasing time from the SCT, and in the third cycle
      reached an order of magnitude as in high-dose IL-2 patients without SCT. Together
      with the abundant in vitro data, these findings may help devise a combination
      immunotherapy permitting stronger anti-tumor effects, but lesser adverse effects.

PMID- 10918411
TI  - An infant with severe combined immunodeficiency syndrome, an alpha-thalassemia
      trait and renal Fanconi syndrome.
AB  - We describe an infant with severe combined immunodeficiency syndrome and an alpha
      thalassemia trait who developed a renal Fanconi syndrome after his first stem
      cell transplantation. This syndrome consists of a generalized failure of proximal
      tubular reabsorption, which leads to a large number of metabolic disturbances.
      The etiology varies from inherited causes, including an idiopathic form, to
      acquired causes such as intoxications, immunological disorders and
      hemoglobinopathies. In this case report we discuss possible explanations of the
      Fanconi syndrome in our patient.

PMID- 10918412
TI  - Agrobacterium yellow group: bacteremia and possible septic arthritis following
      peripheral blood stem cell transplantation.
AB  - A 47-year-old male patient developed sepsis and monoarticular arthritis following
      autologous stem cell transplantation for recurrent Hodgkin's disease. Blood
      cultures were positive for Agrobacterium yellow group. The knee pain and swelling
      responded promptly to the institution of empirical broad-spectrum antibiotics.
      Recurrent bacteremia developed necessitating Hickman line removal for eventual
      resolution of the infection. Transplant physicians should be aware of this
      unusual pathogen and the potential for both persistent line-related sepsis and
      possible septic arthritis.

PMID- 10918413
TI  - Late onset cyclosporine-induced cerebral blindness with abnormal SPECT imagings
      in a patient undergoing unrelated bone marrow transplantation.
AB  - A 23-year-old woman underwent HLA-matched unrelated BMT for CML. She developed
      cerebral blindness on day 81. Brain magnetic resonance imaging revealed
      hyperintensity on a T2-weighted image in the white and gray matter of the right
      frontal and both occipital lobes. Single-photon emission computed tomography
      (SPECT) was consistent with a decrease in radionuclide uptake in these areas,
      suggesting a vasoconstrictive mechanism. A diagnosis of CsA-induced
      encephalopathy was made and CsA was discontinued. Her vision recovered completely
      after 24 h and abnormal imaging resolved within 2 weeks. This case demonstrates
      late onset CsA-induced cerebral blindness with the previously unreported
      abnormalities on SPECT.

PMID- 10918414
TI  - Acute pancreatitis during immunosuppression with tacrolimus following an
      allogeneic umbilical cord blood transplantation.
AB  - Tacrolimus is increasingly used for graft-versus-host disease (GVHD) prophylaxis
      and therapy in the allogeneic stem cell transplant (allo-SCT) setting.
      Pancreatitis, previously described as a side-effect of cyclosporine, has not been
      reported in allo-SCT recipients receiving tacrolimus. We present here a case of
      acute pancreatitis in a 28-year-old patient with chronic myelogenous leukemia
      (CML) who received an unrelated umbilical cord blood transplant (UCBT) and
      tacrolimus for GVHD prophylaxis. On day +31 post-transplant, she developed severe
      acute pancreatitis with multiorgan failure, from which she recovered completely.
      Tacrolimus was the probable cause of pancreatitis in this patient.

PMID- 10918416
TI  - Response

PMID- 10918417
TI  - Hepatitis B viremia in a patient with documented previous HBV immunity after
      autologous transplantation of highly purified PBSC.

PMID- 10918418
TI  - Response

PMID- 10918415
TI  - Pre-emptive ribavirin for 'RSV' in BMT.

PMID- 10918419
TI  - Infusion-related side-effects in children undergoing autologous hematopoietic
      stem cell transplantation for acute leukemia.

PMID- 10918420
TI  - Dose-reduced conditioning for allogeneic blood stem cell transplantation: durable
      engraftment without antithymocyte globulin.
AB  - Between February 1998 and October 1999, 24 patients with advanced leukemia,
      lymphoma or solid tumors received G-CSF mobilized peripheral blood stem cells
      (PBSC) from HLA-matched sibling donors after dose-reduced conditioning therapy.
      Only patients with reduced performance status or major infectious complications,
      not eligible for standard transplant procedures, were included. The 5-day
      conditioning therapy consisted of 3.3 mg/kg intravenous busulphan x 2 days and 30
      mg/m2 fludarabine x 5 days. GVHD prophylaxis was performed with either CsA alone
      (n = 5), CsA combined with short course methotrexate (n = 5) or mycophenolate
      mofetil (n = 14). The day 100 survival was 95.2% for the whole group. All
      patients engrafted after a median of 15 days (range, 11-19) and 12.5 days (range,
      10-19) for neutrophils and platelets, respectively. The median time to a
      neutrophil count of <0.5 x 109/l was 7 days (range, 2 to 12). Acute GVHD >I was
      observed in six patients, whereas eight patients have signs of chronic GVHD. The
      prospective 12 month overall survival with a median follow-up of 7 months is 63%.
      Relapse of disease and toxicity associated with chronic GVHD were the main causes
      of death. The treatment-related mortality was 12.5%. Dose-reduced conditioning
      using intravenous busulphan and fludarabine allows stable engraftment without ATG
      in related transplants and leads to a reduction of transplant-related mortality.

PMID- 10918421
TI  - Mobilization kinetics of peripheral blood progenitor cells after IAPVP-16 salvage
      chemotherapy plus G-CSF in lymphoproliferative disorders.
AB  - We have explored the efficacy of salvage chemotherapy combination, IAPVP-16
      (ifosfamide 5 g/m2 on day 1; VP-16 100 mg/m2 on days 1-3; ara-C 1.2 g/m2/12 h on
      days 1 and 2; methylprednisolone 80 mg/m2 on days 1-5) plus G-CSF for PBPC
      mobilization. This protocol was used in 45 patients with relapsed or refractory
      lymphoproliferative diseases who underwent 85 leukaphereses. In 41 patients > 2 x
      106/kg CD34+ cells were obtained after a median of two procedures. The median
      number of CD34+ cells harvested was 3.2 x 106/kg per apheresis and 8.4 x 106/kg
      per patient. Seven of 10 patients who had failed previous mobilization attempts
      achieved more than 2 x 106 CD34+ cells/kg in a maximum of three aphereses. A
      history of previous mobilization failure and a low platelet count (<150 x 109/l)
      negatively influenced the CD34+ cell yield in univariate and multivariate
      analyses. A good correlation was found between the circulating CD34+ cells/microl
      and the CD34+ cells and CFU-GM in the leukaphereses products (r = 0.93 and r =
      0.73, P < 0.001), and > or =17 CD34+ cells/microl predicted the achievement of >
      2 x 106/kg CD34+ cells in a single leukapheresis in more than 90% of cases. IAPVP
      16 plus G-CSF may be specially indicated in tandem transplantations or CD34+
      selection and in patients who have failed previous mobilization attempts.

PMID- 10918422
TI  - The feasibility of high-dose chemotherapy in breast cancer patients with impaired
      left ventricular function.
AB  - Breast cancer patients with cardiac disease are usually excluded from clinical
      trials of high-dose chemotherapy. We treated 52 patients with inflammatory and/or
      metastatic disease with sequential high-dose melphalan and stem cell rescue
      followed by high-dose thiotepa and stem cell rescue. Stem cells were mobilized
      with cyclophosphamide and/or paclitaxel and filgrastim. Left ventricular ejection
      fraction (LVEF) was measured by equilibrium radionuclide angiocardiography (ERNA)
      at baseline, after each course of chemotherapy and 4 weeks after completing both
      transplants. The mean absolute decrease in LVEF after the two transplants was
      3.6% (P = 0. 008 for the comparison with baseline LVEF), and most of this drop (
      2.5%, P = 0.007) occurred after mobilization. Unexpectedly, paclitaxel was
      associated with a mean absolute decrease in LVEF of 3. 4% (P = 0.032, n = 19),
      cyclophosphamide alone was not associated with a significant change in LVEF (
      1.3%, P = 0.23), but mobilization with sequential paclitaxel and cyclophosphamide
      resulted in a mean absolute drop of 4.9% in LVEF (P = 0.009). Twelve patients
      were found to have a reduced LVEF (<50%) at least once during treatment and had a
      mean absolute decrease in LVEF of 10% (P = 0.008) from baseline, compared with a
      drop of only 1.8% (P = 0. 176) in the patients without impaired LV function.
      Although two of these 12 patients developed symptomatic heart failure, their
      cardiac symptoms were easily treated and there were no cardiac deaths. We
      conclude that our protocol has acceptable cardiac toxicity and breast cancer
      patients with impaired LV function should not be denied high-dose chemotherapy if
      otherwise indicated.

PMID- 10918423
TI  - Phase 1 study of pegylated recombinant human megakaryocyte growth and development
      factor (PEG-rHuMGDF) in breast cancer patients after autologous peripheral blood
      progenitor cell (PBPC) transplantation.
AB  - Forty-seven patients with stage II, III, or IV breast cancer undergoing
      autologous peripheral blood progenitor cell (PBPC) transplantation were
      randomized to placebo (n = 13) or to one of five sequential dose cohorts of
      pegylated (PEG) recombinant human megakaryocyte growth and development factor
      (PEG-rHuMGDF) (1.0, 2.5, 5.0, 7.5, or 10.0 microg/kg/day) (n= 34). Blinded study
      drug was started on the day of transplantation and was continued until the
      platelet count was > or =100 x 109/l or a maximum of 21 days. PBPCs were
      mobilized with filgrastim (r-metHuG-CSF) and all patients received filgrastim
      starting on day +2 after transplantation. The nadir platelet count was not
      affected by treatment. The median time to platelet recovery was 11 and 12 days
      for the placebo and combined PEG-rHuMGDF groups, respectively. No trends in
      adverse events suggested dose- or treatment-related toxicity. Two patients
      withdrew from the study because of an adverse event (allergic reaction in the 7.5
      microg/kg group) probably related to study drug, and veno-occlusive disease (VOD)
      (in the 5 microg/kg group) which was felt not to be related to study drug by the
      investigator. No patients developed neutralizing antibodies to MGDF. Day +21 and
      day +28 platelet counts were higher in the group receiving PEG-rHuMGDF (246 vs
      148 x 109/l and 299 vs 145 x 109/l, respectively; both P < 0. 05). PEG-rHuMGDF up
      to 10 microg/kg/day was well tolerated. In this study, there was no effect of
      study drug on initial platelet engraftment at the doses studied. However, the
      efficacy of other doses is unknown.

PMID- 10918424
TI  - High frequency of extramedullary relapse of acute leukemia after allogeneic bone
      marrow transplantation.
AB  - We investigated the frequency and mode of relapses of acute leukemia after
      allogeneic BMT in a series of 50 consecutive patients. The median age of patients
      was 31.5 years with 26 males. Thirty-two patients had AML. Forty-three patients
      were in first CR. All patients received BuCy regimen with GVHD prophylaxis of
      cyclosporine plus methotrexate. After a median follow-up time of 22.4 months
      (range, 6.0-52.9), 14 patients (28%) relapsed. Seven patients (50%) relapsed in
      the bone marrow only; three (21%) relapsed in extramedullary sites only; and four
      (29%) relapsed in both extramedullary sites and bone marrow. Times to relapses in
      bone marrow only (median 6.3 months) were significantly shorter when compared to
      times to extramedullary relapses with or without bone marrow involvement (median
      12.3 months, P = 0.048). Sites of extramedullary relapses varied widely among the
      patients. In conclusion, we observed a high frequency of extramedullary relapses
      of acute leukemia after allogeneic BMT (50%). The GVL effect observed in the
      extramedullary sites of the body may not be as effective as in the bone marrow in
      patients with acute leukemia after allogeneic BMT.

PMID- 10918425
TI  - High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow
      rescue for the treatment of high risk central nervous system tumors.
AB  - Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37),
      medulloblastoma (n = 2) or non-biopsied tumors (n = 3) with supratentorial (n =
      24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were
      eligible for this study with adequate organ function and no bone marrow tumor
      infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600
      mg/m2 BCNU, 900 mg/m2 thiotepa and 1500 or 750 mg/m2 etoposide (VP-16) was
      administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one
      newly diagnosed patients received local irradiation (RT) post ABMR. Nine early
      deaths were observed (21%), as well as one secondary graft failure. Half of the
      patients aged 18 years or older experienced toxic deaths, whereas only 15% of
      patients younger than 18 years experienced toxic death (P = 0.05). Of 25
      evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4%
      partial remission (PR), while 28% remained in continuing complete remission (CCR)
      and 44% remained with stable disease prior to RT. Of eight evaluable patients
      with recurrent disease, one achieved CR and two PR, while one remained in CCR and
      four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and
      17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and
      one patient treated for recurrent disease being alive, without disease
      progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The
      combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but
      definite activity for high risk CNS tumors. Similar protocols with lower toxicity
      merit further evaluation in both newly diagnosed and recurrent CNS tumors.

PMID- 10918426
TI  - Tacrolimus (FK506) and methotrexate as prophylaxis for acute graft-versus-host
      disease in pediatric allogeneic stem cell transplantation.
AB  - Currently, limited data exist on the role of tacrolimus (FK506) in pediatric
      allogeneic marrow transplantation. Forty-one patients who received tacrolimus as
      prophylaxis were reviewed, with a median age of 9 years (range 0.2-16 years).
      Twenty-one patients underwent related donor transplants and 20 underwent
      unrelated donor transplants. All patients received tacrolimus beginning the day
      prior to transplant at a dose of 0.03 mg/kg/day by continuous i.v. infusion. When
      clinically possible, patients were switched to oral therapy in two divided doses,
      at four times the intravenous dose. Tacrolimus levels were monitored twice a
      week, and dosages adjusted to maintain serum levels 5-15 ng/ml. Common adverse
      effects included hypomagnesemia (98%), hypertension (49%), nephrotoxicity (34%),
      and tremors (32%). Less common side-effects (<10% cases) included seizures and
      hyperglycemia. The median time to ANC recovery (ANC >500 x 106/l) was 15 days.
      For the related donor group, the incidence of grade II-IV acute GVHD was 33%, and
      grade III-IV GVHD 19%. For the unrelated donor group, the incidence of grade II
      IV acute GVHD was 55%, and grade III-IV GVHD 30%. Overall, tacrolimus therapy was
      well tolerated as prophylaxis for acute GVHD in pediatric patients undergoing
      allogeneic transplantation.

PMID- 10918427
TI  - Immune reconstitution following high-dose chemotherapy with stem cell rescue in
      patients with advanced breast cancer.
AB  - The present study examines the nature of humoral and cellular immune
      reconstitution in 28 patients with advanced breast cancer following high-dose
      chemotherapy with stem cell rescue. Patients underwent testing of T, B, NK and
      dendritic cell function at serial time points until 1 year post transplant or
      until the time of disease progression. Abnormalities in T cell phenotype and
      function were observed following high-dose chemotherapy that persisted for at
      least 6-12 months. The vast majority of patients experienced an inversion of the
      CD4/CD8 ratio and demonstrated an anergic response to candida antigen. Mean T
      cell proliferation in response to PHA and to co-culture with allogeneic monocytes
      was significantly compromised. In contrast, mean IgG and IgA levels were normal 6
      months post transplant and NK cell yields and function were transiently elevated
      following high-dose chemotherapy. Dendritic cells generated from peripheral blood
      progenitors displayed a characteristic phenotype and were potent inducers of
      allogeneic T cell proliferation in the post-transplant period. The study
      demonstrates that patients undergoing autologous transplantation for breast
      cancer experience a prolonged period of T cell dysfunction. In contrast, B, NK,
      and DC recover more rapidly. These findings carry significant implications for
      the design of post-transplant immunotherapy.

PMID- 10918428
TI  - Reconstitution of gammadelta T cell repertoire diversity after human allogeneic
      hematopoietic cell transplantation and the role of peripheral expansion of mature
      T cell population in the graft.
AB  - We have examined the reconstitution of gammadelta T cell repertoire diversity
      after human allogeneic hematopoietic cell transplantation using a polymerase
      chain reaction (PCR)-based complementarity-determining region (CDR) 3 size
      spectratyping and DNA sequencing. The CDR3 complexity in the variable region of
      the T cell receptor (TCR)-delta chain was different amongst the individuals
      studied. Furthermore, CDR3 size distribution patterns of allogeneic hematopoietic
      cell transplant recipients were almost completely recovered by a few months after
      transplantation. In some patients, clonal predominance of the TCRDV1+ T cells
      became evident during the period after transplantation. In one particular
      donor/recipient pair, clonal predominance of TCRDV1+ T cells was already present
      in blood lymphocytes of the donor, and was also observed in the recipient after
      transplantation. Using this donor/recipient pair, we have questioned whether
      gammadelta T cell regeneration occurs via the peripheral expansion of mature T
      cells in the graft. In the donor lymphocytes, two expanding gammadelta T cell
      clones, which were demonstrated by CDR3 sequences of the TCR-delta chain, were
      recognized. These two clones were identified in the T cells from the recipient
      post transplant, but not before transplantation. One of the two clones was still
      detectable 1(1/2) years after the transplant procedure. These results strongly
      suggest that peripheral expansion of mature T cells in the graft is the principal
      pathway of gammadelta T cell regeneration after allogeneic hematopoietic cell
      transplantation in adults.

PMID- 10918429
TI  - Cardiac systolic function before and after hematopoietic stem cell
      transplantation.
AB  - In order to examine the effect of hematopoietic stem cell transplantation (HSCT)
      on cardiac systolic function, we measured left ventricular ejection fraction
      (LVEF) by radioventriculography (RVG) before and after the transplantation
      procedure. One hundred and forty-eight patients were examined, 96 undergoing
      allogeneic grafting and 52 autologous. Fifty patients had CML, 48 AML, 21 ALL, 18
      multiple myeloma and 11 breast cancer. The second RVG examination was performed
      22 to 227 days (median 60 days) after HSCT. The mean LVEF value in the whole
      patient group was 60.2% (range 39-81%) before and 61.1% (35-86%) after
      transplantation. Patients with CML had significantly higher LVEF before
      transplantation than patients with acute leukemia (P = 0.007) and multiple
      myeloma (P = 0.005). No significant changes in mean LVEF between the pre- and
      post-transplant measurements were seen in any of the diagnostic subgroups or in
      allogeneic or autologous recipients. None of the 148 patients in the study has
      shown any signs of clinical heart failure at 2, 5 to 10 years follow-up. Patients
      who had received anthracyclines in the previous treatment had significantly lower
      LVEF before transplantation but showed no increased risk of decline in cardiac
      function. In conclusion, the HSCT procedure does not seem to affect myocardial
      function 1-7 months after transplantation.

PMID- 10918430
TI  - Liver disease during the first post-transplant year in bone marrow
      transplantation recipients: retrospective study.
AB  - Liver dysfunction is a common problem in BMT recipients and it is important to
      determine the etiology in order to institute appropriate therapy. The purpose of
      this study was to evaluate the possible causes of liver dysfunction during the
      first post-transplant year in BMT recipients and to identify a possible
      relationship between pre-existing liver dysfunction and viral hepatitis with
      prognosis after BMT. We reviewed liver status before and after BMT in 130
      consecutive patients at the Catholic Hematopoietic Stem Cell Transplantation
      Center. Liver dysfunction during the first post-transplant year occurred in 85
      out of 101 (84. 2%) allogeneic BMT recipients and 13 out of 29 (44.8%) autologous
      BMT recipients. In allogeneic BMT, GVHD and drug hepatotoxicity were major
      causes. In autologous BMT, drug hepatotoxicity was the most common cause.
      Eighteen out of 130 patients (13.8%) had abnormal liver function tests before
      BMT. These patients did not have an increased risk of post-transplant liver
      dysfunction, GVHD, and death compared to patients who had normal liver function
      tests prior to BMT. Nine patients were hepatitis B antigen positive and three
      patients were anti-HCV positive prior to BMT. There was no significant increase
      in the incidence of post-transplant liver dysfunction, GVHD, and death in these
      patients.

PMID- 10918431
TI  - Early intervention in post-transplant lymphoproliferative disorders based on
      Epstein-Barr viral load.
AB  - Using a real-time quantitative PCR assay, we identified two patients with EBV
      related lymphoproliferative disorders at a very early stage. Both had received an
      unmanipulated bone marrow transplant with anti-thymocyte globulin for
      conditioning. To estimate virus-specific immunity, the frequencies of EBV
      specific CD8+ T cells were measured using an enzyme-linked immunospot assay. The
      frequencies of EBV-specific CD8+ T cells of the two were 3.2 and 7.7%,
      respectively, which had possibly expanded in vivo. After withdrawing the
      immunosuppressive agents or administering donor lymphocytes transfusion, their
      symptoms regressed in parallel with the viral load.

PMID- 10918432
TI  - Double-blind, randomized, parallel-group study on the efficacy and safety of oral
      granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in
      patients receiving hyperfractionated total body irradiation.
AB  - The efficacy and safety of granisetron and ondansetron for the prophylaxis of
      nausea and vomiting resulting from hyperfractionated total body irradiation (TBI)
      were assessed. Thirty-four patients randomly received double-blind, oral
      granisetron (2 mg, 1 h before first daily fraction of radiation) or ondansetron
      (8 mg, 1.5 h prior to each fraction of TBI). Ninety patients who received the
      same TBI regimen prior to bone marrow transplantation (BMT), but no 5-HT3
      receptor antagonist, were identified and comprised the historical control group.
      By design, this study was only powered to show a difference between each of the
      active treatment groups and the historical control group. Significantly more
      patients given granisetron (33.3%) or ondansetron (26.7%) had zero emetic
      episodes over 4 days, the primary efficacy end point, than those in the
      historical control group (0%) (P < 0.01; intent-to-treat). Secondary efficacy end
      points were also evaluated. During the first 24 h, significantly more patients
      taking granisetron (61.1%) or ondansetron (46.7%) had zero emetic episodes than
      patients in the historical control group (6.7%) (P < 0.01). Complete emetic
      control (no emesis or rescue antiemetic) over 4 days was more frequent in
      patients taking granisetron (27.8%) or ondansetron (26.7%) compared with the
      historical control group (0%) (P < 0.01). Significantly fewer patients taking
      granisetron (18/18), but not those taking ondansetron (12/15), experienced more
      than five emetic episodes during the 4 days of the study compared with the
      historical control group (40/90; P < 0.01). Oral granisetron and ondansetron are
      safe and effective for the prevention of nausea and vomiting resulting from TBI.

PMID- 10918433
TI  - Febrile neutropenia in allogeneic and autologous peripheral blood stem cell
      transplantation and conventional chemotherapy for malignancies.
AB  - The risk and outcome of infection in febrile neutropenic patients is mainly
      determined by the duration of neutropenia, the underlying disease or the
      treatment. This study was undertaken to compare infections and the outcome after
      conventional chemotherapy (CCT), allogeneic PBSC transplantation (alloPBSCT) or
      autologous PBSC transplantation (autoPBSCT), during the period of neutropenia, in
      a single center. A total of 145 patients (50 in CCT group, 50 in alloPBSCT and 45
      in autoPBSCT) were evaluated. In the alloPBSCT group, 86% of the patients
      (43/50), in the autoPBSCT group 93% of the patients (42/45) and in the CCT group
      92% (46/50) of the patients had at least one febrile episode during their
      neutropenic period (P > 0.05). Microbiologically and/or clinically documented
      infection rates were 50% (25/50), 42% (19/45) and 48% (24/50) respectively. Gram
      positive pathogens, mostly coagulase-negative staphylococci were the most
      frequent cause of bacteremias in all groups. The frequency of CNS infections was
      significantly higher in the alloPBSCT and autoPBSCT groups compared to the CCT
      group (P < 0. 008 and P < 0.04, respectively). Catheter infections were frequent
      in the PBSCT groups and pulmonary infections were more frequent in the CCT group
      (P < 0.05). The CCT group needed longer antibiotic usage compared to the
      alloPBSCT group (P < 0.006). The duration of neutropenia and the type of
      treatment given, does not affect the rate of febrile episodes, but affects the
      type of infections in febrile neutropenic patients.

PMID- 10918434
TI  - Severe oesophagitis after allogeneic bone marrow transplantation for Fanconi's
      anemia.
AB  - Allogeneic bone marrow transplantation (BMT) is an effective treatment for
      Fanconi's anemia (FA) but it requires a dose reduction of alkylating agents used
      for conditioning because of the increased sensitivity of FA cells to DNA cross
      linking agents. Oesophageal damage has not previously been described as a
      complication after allogeneic BMT for this indication. We report five cases of
      severe oesophagitis with stenosis in patients transplanted for FA. It occurred
      either early, or more surprisingly, several years after BMT and could have easily
      been misdiagnosed. It could be explained by hypersensitivity of the FA mucosal
      cells to cytotoxic agents despite the reduced doses of cyclophosphamide and
      irradiation or to non diagnosed congenital abnormalities of the oesophagogastric
      junction. However, the evolution of the oesophageal disease was favorable in all,
      and none of the patients developed secondary cancer. Awareness of this
      complication will lead to earlier diagnosis and treatment of oesophageal stenosis
      and related malnutrition.

PMID- 10918436
TI  - Brucellosis transmitted by bone marrow transplantation.
AB  - We report a unique case of brucellosis transmitted by BMT. An 8-year-old boy with
      the diagnosis of Fanconi's anemia received an allogeneic BMT from his HLA
      identical sibling. Routine culture from the infused marrow suspension grew
      Brucella abortus on day +4 post BMT. Spiking fevers occurred on days +2 and +16.
      The first febrile episode responded to broad-spectrum antibiotic therapy.
      However, the second episode did not. B. abortus was isolated from blood cultures
      taken during the second febrile episode. The Brucella agglutination titer was
      negative. Antibiotic therapy with oral doxycycline and i.v. gentamycin was
      successful with no recurrence of infection during 13 months of follow-up. The
      donor's blood culture was also positive for B. abortus and Brucella antibodies
      were detectable at 1:320 titer when he presented with fever and
      hepatosplenomegaly on day +32. We emphasize the need to consider brucellosis in
      patients undergoing BMT. We suggest that donor and recipient be evaluated for
      brucellosis especially in countries where the incidence of this infection is
      relatively high.

PMID- 10918435
TI  - Long-term follow-up of two children with a variant of mild autosomal recessive
      osteopetrosis undergoing bone marrow transplantation.
AB  - Malignant autosomal recessive (AR) osteopetrosis represents an absolute
      indication for bone marrow transplantation (BMT). Over the last 15 years, almost
      100 BMTs for osteopetrosis have been reported. The median age at transplant of
      most patients is 4 months. Very few cases of mild AR osteopetrosis have been
      described. Here, we report the good outcome of two cases of mild AR osteopetrosis
      with a follow-up of 5 and 6 years, respectively, after an HLA-identical sibling
      transplant undergone at 5 and 12 years of age, respectively. At the time of BMT,
      severe visual impairment was present in both children. Bone biopsy demonstrated
      hypermineralization with virtual obliteration of the medullary spaces, rare
      microfoci of hematopoiesis and marked deficiency in osteoclastic activity.
      Successful engraftment was complicated by hypercalcemia, controlled by a
      combination of bisphosphonate, phosphate infusions, vigorous hydration and
      calcitonin. Following BMT, radiological and histological findings showed
      extensive bone resorption with marked augmentation of the osteoclasts in
      normalized marrow. No improvement was observed in visual acuity, despite complete
      remodeling of skeletal abnormalities. We conclude that allogeneic BMT is the only
      chance of curing mild AR osteopetrosis.

PMID- 10918437
TI  - Successful autologous bone marrow transplant without the use of blood product
      support.
AB  - We describe a successful autologous bone marrow transplant without the use of any
      blood products. The patient had relapsed large cell lymphoma. He was a Jehovah's
      Witness and would not accept transfusions of red blood cells or platelets. He
      enrolled in our Bloodless Medicine and Surgery Program and was maintained on a
      regimen of erythropoietin, iron, Amicar, and G-CSF throughout the transplant. He
      tolerated the transplant well and is alive with no evidence of disease 10 months
      after autografting.

PMID- 10918438
TI  - Inappropriate antidiuretic hormone secretion, abdominal pain and disseminated
      varicella-zoster virus infection: an unusual triad in a patient 6 months post
      mini-allogeneic peripheral stem cell transplant for chronic myeloid leukemia.
AB  - Severe abdominal pain followed by inappropriate antidiuretic hormone secretion
      (SIADH) preceding by several days the skin manifestation of varicella-zoster
      virus (VZV) infection in an immunocompromised patient is described. This is a
      rare presentation of a severe infection described previously only once in a
      chronic myeloid leukemia (CML) patient 5 months post allo-BMT during
      immunosuppressive treatment with cyclosporin A. This is the first case described
      in the setting of non-myeloablative preparation with fludarabine and melphalan
      and followed by donor leukocyte infusion (DLI) 2 and 4 months post allo-BMT. The
      influence of these factors on development of VZV virus infection is discussed. We
      also highlight the high incidence and high mortality in VZV infection in
      immunocompromised patients as well as the frequent atypical presentation.

PMID- 10918439
TI  - Unrelated partially matched peripheral blood stem cell transplantation with
      highly purified CD34+ cells in a child with Wiskott-Aldrich syndrome.
AB  - Stem cell transplantation is the only curative approach to the treatment of
      Wiskott-Aldrich syndrome. However, using grafts from partially matched unrelated
      donors is associated with increased risk of graft rejection and graft-versus-host
      disease. In an attempt to prevent these problems, a 6-year-old boy with Wiskott
      Aldrich syndrome lacking a suitable family donor, was transplanted with large
      numbers of unrelated highly purified CD34+ peripheral blood stem cells mismatched
      at one C locus. Conditioning consisted of busulfan 16 mg/kg body weight,
      cyclophosphamide 200 mg/kg body weight and antithymocyte globulin 20 mg/kg body
      weight x 3 days. The boy had a rapid hematopoietic engraftment and showed
      immunologic reconstitution by day +92. Although he did not receive prophylactic
      immunosuppression he did not develop any graft-versus-host disease and is well
      and alive up to now, 25 months after transplantation.

PMID- 10918440
TI  - Erythema exsudativum multiforme induced by granulocyte colony-stimulating factor
      in an allogeneic peripheral blood stem cell donor.
AB  - We describe a healthy peripheral blood stem cell (PBSC) donor who developed a
      cutaneous reaction, erythema exsudativum multiforme, during the administration of
      granulocyte colony-stimulating factor (G-CSF) for mobilization. The cutaneous
      lesions were located on his hips, apart from the site of G-CSF injection.
      Treatment with topical corticosteroid was commenced, and the lesions resolved
      completely within a week. Adverse cutaneous reactions induced by G-CSF have been
      reported infrequently in healthy donors. Further documentation of cases and their
      full evaluation will be of great importance for both physicians and PBSC donor.

PMID- 10918441
TI  - Secondary myelodysplastic syndromes following peripheral blood stem cell
      transplantation: morphological, cytogenetic and clonality evaluation and the
      limitation of FAB criteria.

PMID- 10918442
TI  - Regulation of both apoptosis and cell survival by the v-Src oncoprotein.
AB  - A number of oncogenes alter the regulation of the cell cycle and cell death,
      contributing to the altered growth of tumours. Expression of the v-Src
      oncoprotein in Rat-1 fibroblasts prevented cell cycle exit in response to growth
      factor withdrawal. Here we investigated whether survival of v-Src transformed
      cells in low serum is dependent on v-Src activity. We used a temperature
      sensitive v-Src to study the effect inactivating v-Src on transformed cells
      growing under low serum conditions. We found when we switched off v-Src the cells
      died by apoptosis characterised by activation of caspases and the stress
      activated kinases, JNK (Jun N-terminal kinase) and p38 MAP (mitogen activated
      protein) kinase. We were able to prevent cell death by addition of serum or
      overexpression of Bcl-2. Thus v-Src transformed Rat-1 cells can be protected from
      apoptosis by serum, v-Src, or Bcl-2. We investigated how v-Src protects from
      apoptosis under these conditions. Amongst other effects, v-Src activates two
      kinases which have been shown to protect cells from apoptosis,
      phosphatidylinositol 3-kinase (PI3-K) and extracellular signal-regulated kinase
      (ERK1/2). We found that switching off v-Src led to a decrease in the activity of
      both PI3-K and ERK1/2, however, we found that adding a specific inhibitor of PI3
      K (LY294002) to v-Src transformed Rat-1 cells grown in low serum induced
      apoptosis while a specific ERK kinase (MEK1) inhibitor (PD98059) had no effect.
      This suggests that v-Src protects from apoptosis under low serum conditions by
      activating PI3-K.

PMID- 10918443
TI  - Promotion of growth and apoptosis in c-myc nullizygous fibroblasts by other
      members of the myc oncoprotein family.
AB  - c-myc nullizygous fibroblasts (KO cells) were used to compare the abilities of c
      myc, N-myc and L-myc oncoproteins to accelerate growth, promote apoptosis, revert
      morphology, and regulate the expression of previously described c-myc target
      genes. All three myc oncoproteins were expressed following retroviral
      transduction of KO cells. The proteins all enhanced the growth rate of KO cells
      and significantly shortened the cell cycle transition time. They also accelerated
      apoptosis following serum deprivation, reverted the abnormal KO cell morphology,
      and modulated the expression of previously described c-myc target genes. In most
      cases, L-myc was equivalent to c-myc and N-myc in restoring all of the c-myc
      dependent activities. These findings contrast with the previously reported weak
      transforming and transactivating properties of L-myc. Myc oncoproteins may thus
      impart both highly similar as well as dissimilar signals to the cells in which
      they are expressed.

PMID- 10918444
TI  - Induction of apoptosis in p16INK4A mutant cell lines by adenovirus-mediated
      overexpression of p16INK4A protein.
AB  - The tumor suppressor gene p16INK4A is a cyclin-dependent kinase inhibitor (CDKI)
      and an important cell cycle regulator. We have previously constructed a
      recombinant adenovirus which expresses p16 (Adp16) and shown that infection in a
      variety of human tumor cell lines with this recombinant virus results in high
      levels of p16INK4A protein expression resulting in cell cycle arrest and loss of
      cyclin-cdk activity. Furthermore, adenoviral-mediated overexpression of wild-type
      p16INK4A is more toxic in cancer cells which express mutant forms of p16INK4A
      compared to cancer cell lines containing endogenous wild-type p16. TUNEL assay
      and DAPI staining following infection of MDA-MB 231 breast cancer cells with
      Adp16 indicate that p16INK4A-mediated cytotoxicity was associated with apoptosis.
      This is supported by studies demonstrating a decrease in cpp32 and cyclinB1
      protein levels and induction of poly (ADP-ribose) polymerase (PARP) cleavage
      following infection of MDA-MB-231 cells with Adp16. These results suggest that
      gene therapy using Adp16 may be a promising treatment option for human cancers
      containing alterations in p16 expression.

PMID- 10918445
TI  - Radiation-induced apoptosis in the adult central nervous system is p53-dependent.
AB  - Oligodendrocytes and subependymal cells in the adult CNS have been shown to
      undergo radiation-induced apoptosis. Here, we examined the role of p53 in
      radiation-induced apoptosis in the adult mouse CNS. In the spinal cord of p53+/+
      mice, apoptotic glial cells were observed within 24 h after irradiation, and the
      apoptotic response peaked at 8 h. These apoptotic cells demonstrated the
      immunohistochemical phenotype of oligodendrocytes, and decreased oligodendrocyte
      density was observed at 24 h after 22 Gy. A similar time course of radiation
      induced apoptosis was seen in subependymal cells in the adult mouse brain.
      Radiation-induced apoptosis was preceded by an increase in nuclear p53 expression
      in glial cells of the spinal cord and subependymal cells of the brain. There was
      no evidence of radiation-induced apoptosis in the spinal cord and subependymal
      region of p53-/- animals. We conclude that the p53 pathway may be a mechanism
      through which DNA damage induces apoptosis in the adult CNS.

PMID- 10918446
TI  - Procaspase 3/p21 complex formation to resist fas-mediated cell death is initiated
      as a result of the phosphorylation of p21 by protein kinase A.
AB  - Caspase 3 is an essential factor for Fas-mediated cell death and exists
      endogenously in cells where its activation is suppressed by p21 and ILP. Inside
      the cell, procaspase 3 interacts with p21 on mitochondria. In the present study,
      we investigated the molecular basis for procaspase 3/p21 complex formation.
      During Fas-mediated cell death, mitochondria are damaged, accompanied by
      decreased mitochondrial membrane-potential and decreased intracellular ATP
      levels. This mitochondrial damage occurs before an estrangement of the procaspase
      3/p21 complex, and we demonstrate that intracellular ATP-deprivation also
      initiates an estrangement of procaspase 3/p21 complex formation and accelerates
      Fas-mediated cell death. In addition, our current results revealed that the
      phosphorylated p21 by PKA interacts with procaspase 3. Here, we report that the
      mitochondrial role, especially for ATP synthesis, and PKA are necessary for the
      procaspase 3/p21 complex formation to resist Fas-mediated cell death.

PMID- 10918447
TI  - Cell cycle progression and apoptosis after irradiation in an acidic environment.
AB  - We investigated the effect of an acidic environment on the radiation-induced G2/M
      arrest and apoptosis using RKO.C human colorectal cancer cells expressing wild
      type p53 and RC10.1 cells, a subline of RKO.C cells deficient in p53 as well as
      p53+/+ MEFs and p53-/- MEFs (mouse embryonic fibroblasts). The cells were
      irradiated with 4 Gy or 12 Gy of gamma-rays in pH 7.5 medium or pH 6.6 medium.
      p53 accentuated the progression of cells from radiation-induced G2/M arrest to
      apoptosis and the pH 6.6 environment suppressed the progression of cells through
      G2/M-phase to apoptosis after irradiation. Further analysis indicated that the
      radiation-induced G2/M arrest was due mainly to G2 arrest in both pH 7.5 and pH
      6.6. Therefore, it was concluded that p53 enhances, and an acidic environment
      suppresses, the exit of cells from radiation-induced G2 arrest by altering cyclin
      B1-Cdc2 kinase activity.

PMID- 10918448
TI  - Prevention of toxin-induced cytoskeletal disruption and apoptotic liver cell
      death by the grapefruit flavonoid, naringin.
AB  - The protein phosphatase-inhibitory algal toxins, okadaic acid and microcystin-LR,
      induced overphosphorylation of keratin and disruption of the keratin cytoskeleton
      in freshly isolated rat hepatocytes. In hepatocyte cultures, the toxins elicited
      DNA fragmentation and apoptotic cell death within 24 h. All these toxin effects
      could be prevented by the grapefruit flavonoid, naringin. The cytoprotective
      effect of naringin was apparently limited to normal hepatocytes, since the toxin
      induced apoptosis of hepatoma cells, rat or human, was not prevented by the
      flavonoid.

PMID- 10918449
TI  - Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of
      the AP-1 transcription factor and downregulation of Bcl-2.
AB  - Galectins are emerging as a new class of bioactive molecules with specific
      immunomodulatory properties. Galectin-1 (Gal-1), a member of this family, has
      been shown to induce apoptosis of mature T cells and immature thymocytes. To gain
      insight into the intracellular signals transduced by Gal-1 upon binding to mature
      T cells, we investigated whether this protein triggered activation of the dimeric
      AP-1 transcription factor. A marked increase in the binding of nuclear extracts
      to synthetic oligonucleotides containing the AP-1 consensus sequence, could be
      detected by an electrophoretic mobility shift assay, when T cells were cultured
      for 30 min in the presence of Gal-1. This DNA-binding activity was preceded by a
      rapid increase in the levels of c-Jun mRNA, as determined by Northern blot
      analysis. Requirement of AP-1 for Gal-1-induced apoptosis was confirmed by the
      dose-dependent reduction on the level of DNA fragmentation observed when cells
      were pre-treated with curcumin (an inhibitor of AP-1 activation) before exposure
      to Gal-1. Finally, evidence is also provided by Western blot analysis, showing
      that Gal-1 inhibits Concanavalin A (Con A) induction of Bcl-2 protein. Results
      presented in this study provide the first experimental evidence regarding AP-1
      and Bcl-2 as targets of the signal transduction pathway triggered by Gal-1 and
      set the basis for a more in depth understanding of the molecular mechanisms of T
      cell death regulation.

PMID- 10918451
TI  - Committee on Publication Ethics (COPE). Guidelines on good publication practice.

PMID- 10918450
TI  - How often should we take bitewing radiographs?

PMID- 10918452
TI  - Computed tomography of emphysema following tooth extraction.
AB  - Subcutaneous and tissue space emphysema following surgical extraction of
      mandibular third molars is a rare and serious complication of dental surgery.
      Recognition of mediastinal emphysema following surgical extraction is difficult
      because there are no absolute clinical symptoms and signs. We present two cases
      of emphysema following extraction of a lower third molar and discuss the
      contribution of CT to the early recognition of the presence and spatial migration
      of air and to clinical management.

PMID- 10918453
TI  - Basic study of the measurement of bone mineral content of cortical and cancellous
      bone of the mandible by computed tomography.
AB  - OBJECTIVES: To develop an algorithm for automatic separation of cortical from
      cancellous bone in the mandible and for measuring mandibular bone mineral content
      (BMC). METHODS: A dried mandible was scanned together with a reference phantom by
      spiral CT. A new algorithm was developed specifically for the mandible and cross
      sectional images reconstructed in the buccolingual plane. The cortical bone was
      extracted with a threshold of 80% of the peak height in the line-scan profile and
      the cancellous bone extracted separately. The volume and BMC were estimated.
      Images of cortical and cancellous bone were displayed in a plane approximating
      the orientation used for dental radiography and BMC expressed as aluminium
      equivalents (Al-eqs). RESULTS: The ratio of cortical to cancellous bone by volume
      was 22:78, and the ratio of the BMC 60:40. Comparison of BMC from reconstructed
      CT with Al-eqs showed good correlation but was 1.5 times higher with CT.
      CONCLUSIONS: It is possible to separate cancellous from cortical bone
      automatically from CT images and to measure the BMC.

PMID- 10918454
TI  - Comparison of observer performance in determining the position of endodontic
      files with physical measures in the evaluation of dental X-ray imaging systems.
AB  - OBJECTIVE: To examine the feasibility of substituting observers determining the
      accuracy of endodontic measurements for measurements of physical qualities in
      comparison of digital imaging systems. METHODS: Sensors from six digital imaging
      systems were compared for signal-to-noise ratio (SNR), modulation transfer
      function (MTF) and detective quantum efficiency (DQE). A total of 45 canals in
      teeth from human cadavers were instrumented to their apical foramina. Endodontic
      files, ranging in size from size 8 to size 20, were glued in place at random
      distances from the apical foramina spanning a range of +/- 3 mm. The teeth were
      imaged with the six digital systems and dental X-ray film. Fifteen dentists
      independently measured the distance from the end of the file to the apical
      foramen. Results were expressed as the measurement error. Measurement error was
      compared to SNR, MTF and DQE for each digital system. RESULTS: CDR (Schick, New
      York, NY, USA), Digora (Sordex, Helsinki, Finland) and Dexis (Provision Dental
      Systems, Palo Alto, CA, USA) produced the highest SNR values followed closely by
      RVG-4 (Trophy, Croissy-Beavborg, France). Sens-A-Ray (Dent-X/Regam Medical
      Systems, Sundsvall, Sweden), Dexis and the RVG-4 produced the best MTF results.
      Dexis had the greatest DQE. The mean measurement errors (in mm) were: Film 0.65,
      Dexis 0.69, CDR 0.71, RVG-4 0.74, Digora 0.89, Sens-A-Ray 0.97, and Visualix-2
      (Gendex, Monza, Italy) 0.98. CONCLUSIONS: Digital systems closely approximate
      film in their accuracy when used for endodontic measurement providing that the
      assessment instruments have similar resolving power. DQE was the best physical
      predictor of system accuracy when compared with endodontic length measurements.
      MTF and SNR alone did not accurately predict observer precision.

PMID- 10918455
TI  - A comparison of the effect of task-specific with fixed beam alignment in tuned
      aperture computed tomography.
AB  - OBJECTIVES: To test the hypothesis that fixed beam alignment, representative of
      conventional, fixed-projection three-dimensional (3D) imaging systems, yields
      significantly lower detectability of approximal radiolucencies than does a task
      specific strategy that 'opens the contacts'. METHODS: Eleven pairs of extracted
      teeth containing systematically varying numbers of induced approximal low
      contrast defects were evaluated from 3D displays produced by means of tuned
      aperture computed tomography (TACT) under controlled conditions. Each of the
      resulting tomographic presentations was displayed in two random sequences to
      seven trained clinicians. The task-specific (test) series was generated from
      eight different projections varying in vertical disparity but constrained to open
      the contacts. The fixed-aiming (control) series was generated from eight
      projections distributed uniformly on a circle. RESULTS: Accuracy of defect
      detection averaged 5%, significantly higher with task-specific aiming than with
      fixed alignment projection geometry (P = 0.02). All observers unequivocally
      preferred the displays produced from projections with open contacts; however,
      they demonstrated considerable variation in their approach to the task, including
      the time required to interpret the displays. CONCLUSIONS: The improvement in
      observer accuracy obtained from radiographs displayed in three dimensions results
      from an imaging strategy that selectively increases the signal-to-noise ratio in
      regions of interest.

PMID- 10918456
TI  - Clinical evaluation of lymphoscintigraphy with a new technetium compound for
      metastatic cervical lymphadenopathy.
AB  - OBJECTIVES: To evaluate the potential usefulness of lymphoscintigraphy for the
      detection of metastatic cervical lymphadenopathy. METHODS: Dynamic and static
      lymphoscintigraphy with 99Tcm-HSA-D was performed in 23 patients with malignant
      oropharyngeal tumors. The internal jugular nodes were excised and examined
      pathologically. The results of the lymphoscintigraphy were compared with the
      pathological examination and clinical palpation for accuracy. RESULTS: All cases
      showed abnormal findings on lymphoscintigraphy. The accuracy on dynamic
      scintigraphy was 69% for asymmetric drainage, 69% for delayed drainage and 100%
      for inverse drainage. The overall accuracy for each side was 71%. With static
      scintigraphy, the accuracy was 69% for asymmetry, 86% for fitting defect, 67% for
      mottled-patchy appearance, 70% in swelling and 100% for collateral pathway. The
      overall accuracy for each side was 74%. The agreement between lymphoscintigraphy
      and palpation was 44%. CONCLUSIONS: Lymphoscintigraphy with 99Tcm-HSA-D was
      superior to palpation. The method is useful as a supplementary modality for the
      evaluation of metastatic cervical lymphadenopathy because of its relatively high
      accuracy and a low false-negative rate.

PMID- 10918458
TI  - A rare, radiographic 'sunray' appearance in fibrous dysplasia.
AB  - We report a case of a 19-year-old Thai woman who had fibrous dysplasia (FD) with
      a rare radiographic 'sunray' appearance. The sunray appearance could have been
      due to either an unusual pattern of calcification within the lesion or a
      periosteal reaction.

PMID- 10918457
TI  - Computed tomography and ultrasonography of metastatic cervical lymph nodes in
      oral squamous cell carcinoma.
AB  - OBJECTIVES: To define criteria for CT and US in differentiating cervical lymph
      node metastases in oral squamous cell carcinoma (SCC). MATERIALS AND METHODS: CT
      and/or US of 230 metastatic lymph nodes and 228 benign lymph nodes in 147
      patients with oral SCC were retrospectively evaluated. The CT and US findings of
      each lymph node were compared with the histopathological findings. A metastasis
      was defined on CT as a lymph node with rim or heterogeneous enhancement, or
      measuring 10 mm or more in the short axis, regardless of enhancement pattern, and
      on US as having definite internal echoes, regardless of size, or without definite
      internal or hilar echoes, but measuring 10 mm or more in the short axis. A lymph
      node with hilar echoes or a ratio of the long to short axis (L/S ratio) of 3.5 or
      more was considered benign. A lymph node failing to comform to any of these
      categories was termed questionable. RESULTS: The positive predictive value (PPV)
      for CT was 90.8% and the negative predictive value (NPV) was 70.4%. However,
      65.7% of all lymph nodes could not be classified as either metastastic or benign.
      PPV for US was 96.5% and NPV was 88.1%. 25.5% of all lymph nodes could not be
      classified as either metastatic or benign. CONCLUSIONS: Despite limitations in
      detecting metastases, by including a third category 'questionable' our criteria
      appear clinically more useful than other current methods based on two groups
      only.

PMID- 10918459
TI  - A case of glandular odontogenic cyst associated with ameloblastoma: correlation
      of diagnostic imaging with histopathological features.
AB  - The glandular odontogenic cyst (GOC) is a rare odontogenic cyst. There has only
      been one reported case of the simultaneous presence of GOC and ameloblastoma. The
      radiographic features of GOC are well established but the MR findings have not
      been described. We report a case of GOC associated with ameloblastoma with
      special reference to the correlation of the diagnostic imaging with the
      histopathological features.

PMID- 10918460
TI  - In vivo antioxidant effect of green tea.
AB  - OBJECTIVE: The object of this study was to investigate the in vivo antioxidant
      effect of green tea and dosage effect of green tea on antioxidant effect. DESIGN:
      We tested 10 healthy subjects (aged 23-25 y, five women and five men) with
      overnight fasting. The total antioxidant capacity of plasma was measured at
      baseline and 60 min and 120 min after ingestion of 150 ml green tea. Green tea
      was prepared by infusing 2.5 g of dried green tea leaves for 2 min at 80 degrees
      C in 150 ml of water. In the second week, they took 300 ml of tea (5.0 g of green
      tea leaves) and, in the third week, 450 ml of tea (7.5 g of green tea leaves).
      The total antioxidant capacities of plasma were determined with a Total
      Antioxidant Kit (Randox Laboratories Ltd, UK) using a Cobas Mira analyser (Roche
      Diagnostic Systems Inc., Switzerland). The mean intra-assay coefficient of
      variation was 1.2%. RESULTS: The total antioxidant capacity of plasma increased
      by 1.1% at 60 min and 2.1% at 120 min over baseline value in subjects consuming
      150 ml of green tea, which was statistically not significant. However, total
      antioxidant capacity of plasma after consuming 300 ml of green tea showed a
      significant increase of 7.0% after 60 min and 6.2% after 120 min (P<0.0001), and
      after consuming 450 ml 12.0% after 60 min and 12.7% after 120 min over baseline
      value (P<0.0001). CONCLUSIONS: Total antioxidant capacity of plasma was
      significantly increased after taking green tea in amounts of 300 and 450 ml. A
      positive increment according to green tea dosage was also observed. SPONSORSHIP:
      This work was funded by the Pacific Corporation (Korea).

PMID- 10918461
TI  - A comparison of dietary behaviour in Central England and a French Mediterranean
      region.
AB  - BJECTIVEe: The investigation involves comparison of dietary behaviour between UK
      and Mediterranean France by characterizing the pattern of the current French
      Mediterranean diet compared with the current British diet. DESIGN: The findings
      of two dietary surveys, one in the UK and one in France, are compared. An
      interviewer-administered questionnaire was used in both countries. Questions on
      food frequency were used to assess dietary behaviour, which were regrouped in the
      French survey to correspond with UK groupings. Dietary indices were constructed
      to describe dietary behaviour in relation to cancer recommendations for intake of
      fat, fibre, meat, fruit and vegetables. SETTING: The UK study was conducted in
      Leicestershire, central England and the French study was carried out in Herault,
      southern France. SUBJECTS: UK: n=418 subjects (57.9% female and 42.1% male; mean
      age=45.0 y); France: n=635 subjects (50.1% female and 40.9% male; mean age=49.8
      y). Age range of both samples: 20-74 y. RESULTS: There were positive and negative
      trends in food consumption in each country. UK respondents reported eating more
      beans and pulses (P=0.000), less cheese (P=0. 000), red meat (P=0.001), and
      processed meats (P=0.000) than French respondents. However, on the negative side,
      they ate less fruit and vegetables (P=0.000), fish and poultry (P=0.000), cereals
      (P=0.000), and more sweets and chocolates (P=0.000), and cakes, pastries,
      biscuits and puddings (P=0.000). Women had healthier diets in both countries.
      CONCLUSIONS: Overall the southern French diet was healthier as French respondents
      scored significantly better for indices for fat, dietary fibre, fruit and
      vegetables (P=0.000 in all cases). However, the French sample scored poorer for
      the meat index (P=0.000). SPONSORSHIP: This study was supported by a grant from
      l'Association de la Recherche contre le Cancer (ARC) awarded to M Holdsworth.

PMID- 10918463
TI  - Postabsorptive respiratory quotient and food quotient-an analysis in lean and
      obese men and women.
AB  - OBJECTIVE: Macronutrient intake is difficult to measure under free-living
      conditions, because of errors in the reporting of food intake. The aim of the
      current study was to assess whether postabsorptive respiratory quotient (RQ) is
      indicative for the food quotient (FQ), with other factors, such as body
      composition and energy balance, taken into account. SUBJECTS: Thirty lean
      subjects (age 31+/-9 y, body mass index (BMI) 22.0+/-2.1 kg/m2) and 20 obese
      subjects (age 48+/-12 y, BMI 33.3+/-4.4 kg/m2) participated in the study. DESIGN:
      Body mass changes were determined over a 7 day period before the measurement of
      postabsorptive RQ and in this period subjects reported their total food intake in
      a dietary record. A subgroup of 12 lean subjects was supplied with their total
      food intake in this period (twice with different diets). Food quotients were
      calculated from the valid food records (<10% underrecording and undereating).
      Body composition was estimated using the three-compartment model of Siri.
      RESULTS: Postabsorptive RQ was not related to FQ (n=31, r=-0.24, P=0.2) and no
      difference was observed between the two diet periods (n=12 paired t-test, P=0.9).
      Postabsorptive RQ was related to the change in body mass (r=0.57, P=0.0001), but
      not to BMI, fat mass or fat-free mass. CONCLUSIONS: In the present study, the
      energy balance over the days prior to the measurement was the most important
      factor influencing postabsorptive RQ. Postabsorptive RQ was not a reliable
      indicator for habitual FQ even when corrected for energy balance and body
      composition.

PMID- 10918462
TI  - The role of attitudes, intentions and habit in predicting actual consumption of
      fat containing foods in Italy.
AB  - OBJECTIVE: To explore which were the most important predictors of the actual
      consumption of foods containing fat and to test if there were different profiles
      of beliefs and attitudes. DESIGN: A total of 1200 households participated in a
      food consumption survey for 7 days. A questionnaire, containing questions on
      belief, attitude and intention items based on Ajzen and Fishbein's model, was
      completed on the first day of the survey. SETTING: The study was conducted at the
      beginning of 1994 in Italy. SUBJECTS: In all, 860 subjects, randomly selected for
      each household participating in the food consumption survey, were included in
      this study. RESULTS: A cluster analysis based on average daily intake per capita
      of nine types of food containing fats was carried out on 860 subjects. The three
      clusters represented people with different criteria of preference for milk. The
      relationship between the variables was tested using the forward selection method
      in multiple regression. The attitude entered sequentially into the model
      assessing the intention of consuming, after the habit component. Habit was found
      to be the most the most important predictor of the actual consumption of each
      type of food. The intention entered into the equation as predictor of the
      consumption only for butter and olive oil. Habit has been found more important
      than intention in influencing the consumption of all types of food, whereas the
      intention did not enter into the model as determinant of the consumption with
      exception of butter and olive oil in which it remains as a significant predictor.
      CONCLUSIONS: The results of the cluster analysis suggested that subjects of
      cluster 1 might be more concerned about fat intake. The findings of the
      regressions showed that the subjective measure of habit entered in the model as
      the most important predictor of the actual consumption of each type of food. The
      low prediction of the actual consumption indicated that there could be other
      important variables influencing the consumption not included in this study.

PMID- 10918464
TI  - Validation of prediction equations for basal metabolic rate in chinese subjects.
AB  - OBJECTIVES: To examine the validity of existing prediction equations for basal
      metabolic rate (BMR) and two generated regression equations in healthy Chinese
      subjects and patients with chronic diseases. SUBJECTS: One-hundred and thirty
      four healthy Chinese volunteers of aged 16-88 among staff working in Shatin
      Hospital and their relatives, and 30 elderly patients with heart disease, stroke
      and chronic obstructive airway disease (COAD) were recruited. INTERVENTIONS:
      Height, weight, biceps and triceps skinfold thickness, body fat percentage, and
      BMR were measured in the healthy subjects and patients. Two regression equations
      were derived from 70 healthy Chinese subjects. Three existing equations (WHO, Liu
      and Jia equations) and two derived equations were then cross-validated in 64
      subjects and 30 patients. RESULTS: For the healthy Chinese subjects, as well as
      patients, the BMR calculated by Liu was the closest to the measured BMR among all
      the equations, although there was slight underestimation for patients.
      CONCLUSION: This study confirms that the Liu equation is the most appropriate for
      predicting BMR in healthy Chinese subjects, but it underestimates the BMR in
      those with chronic diseases. Fat-free mass is the best predictor of measured BMR.
      SPONSORSHIP: Unrestricted research grant in nutrition from the Bristol-Myers
      Squibb Foundation.

PMID- 10918465
TI  - The use of the Mini-Nutritional Assessment (MNA) tool in elderly orthopaedic
      patients.
AB  - OBJECTIVE: To assess the use of the Mini-Nutritional Assessment (MNA) in elderly
      orthopaedic patients. DESIGN: An observation study assessing the nutritional
      status of female orthopaedic patients. SETTING: The orthopaedic wards of the
      Royal Surrey County Hospital. SUBJECTS: Forty-nine female patients aged 60-103 y;
      dietary records were obtained for 41 subjects and 36 subjects gave a blood sample
      for biochemical analysis. MAJOR OUTCOME METHODS: MNA questionnaire,
      anthropometry, plasma albumin, transferrin, C-reactive protein (CRP) levels and
      dietary analyses. RESULTS: The group as a whole had low mean values for body
      weight, albumin and transferrin and high CRP levels. In addition, the group had
      mean energy intakes well below the estimated average requirement (EAR) and mean
      intakes of vitamin D, magnesium, potassium, selenium and non-starch
      polysaccharides (NSP) were below the lower reference nutrient intakes (LRNI). The
      MNA screening section categorized 69% of the patients as requiring a full
      assessment (scored 11 or below), but for the purposes of the study the MNA was
      completed on all patients. The MNA assessment categorized 16% of the group as
      'malnourished' (scored<17 points), 47% as 'at risk' (scored 17.5-23.5) and 37% as
      'well nourished' (scored>23.5). Significant differences were found between the
      malnourished and well nourished groups for body weight (P<0.001), body mass index
      (BMI) (P<0.001), demiquet (P<0.001) and mindex (P<0. 001). Mean values for energy
      and nutrient intakes showed a clear stepwise increase across the three groups for
      all nutrients except sodium, with significant differences for protein (P<0.05),
      carbohydrate (P<0.05), riboflavin (P<0.05) niacin (P<0.05), pyridoxine (P<0.05),
      folate (P<0.05), calcium (P<0.05), selenium (P<0.05), iron (P<0.05) and NSP
      (P<0.05) intakes. Stepwise multiple regression analysis indicated that
      anthropometric assessments were the most predictive factors in the total MNA
      score. The sensitivity and specificity of the MNA was assessed in comparison with
      albumin levels, energy intake and mindex. The sensitivity of the MNA
      classification of those scoring less than 17 points in comparison with albumin
      levels, energy intake and mindex varied from 27 to 57% and the specificity was 66
      100%. This was compared with the sensitivity and specificity of using a score of
      less than 23.5 on the MNA to predict malnourished individuals. Using this cut-off
      the sensitivity ranged from 75 to 100%, but the specificity declined to between
      37 and 50%. CONCLUSIONS: The results suggest that the MNA is a useful diagnostic
      tool in the identification of elderly patients at risk from malnutrition and
      those who are malnourished in this hospital setting. SPONSORSHIP: Nestle Clinical
      Nutrition, Croydon, Surrey.

PMID- 10918466
TI  - Early linear growth retardation and later blood pressure.
AB  - OBJECTIVE: To examine the effects of stunting in early childhood on blood
      pressure in later childhood. DESIGN: A cohort study. SETTING: Kingston, Jamaica.
      SUBJECTS: Seven to eight year old children, 120 stunted (height for age <-2 s.d.
      of the NCHS references) and 224 non-stunted (height for age >-1 s.d. of the NCHS
      references) at age 9-24 months. METHODS: Stunted and non-stunted children were
      identified at age 9-24 months by house to-house survey of poor neighbourhoods in
      Kingston, Jamaica. Blood pressure and anthropometry were measured at age 7-8 y.
      Birth weight was obtained from hospital records (73%) or maternal recall.
      RESULTS: The stunted children remained shorter and thinner than the non-stunted
      ones. In multiple regression analysis adjusting for size and pulse rate, the
      stunted children had higher systolic blood pressure (P<0.05). Birth weight was
      not a significant predictor of systolic blood pressure. CONCLUSION: Stunting in
      early childhood may increase the risk of elevated systolic blood pressure in
      later life. SPONSORSHIP: Nutricia Research Foundation, The Netherlands and the
      Commonwealth Caribbean Medical Research Council.

PMID- 10918467
TI  - A national study of the prevalence of overweight and obesity in 6-12 y-old Swiss
      children: body mass index, body-weight perceptions and goals.
AB  - OBJECTIVES: To estimate the prevalence of overweight and obesity in Swiss
      children and to obtain information on weight perceptions and weight control
      practices in this population. DESIGN: Cross-sectional, three-stage, probability
      proportionate-to-size cluster sampling. SETTING: Middle schools throughout
      Switzerland. SUBJECTS: A representative national sample of 595 6-12 y-old
      schoolchildren. INTERVENTION: Measurement of weight and height; interview on
      weight perceptions and weight control practices. RESULTS: Body mass index (BMI)
      was calculated and used as an indicator of overweight. The BMIs of the Swiss
      children were compared with US, UK, French and Swiss reference data. Depending on
      which reference data were used, the prevalence of obesity varied between 9.7 and
      16.1% and the prevalence of overweight varied between 21.7 and 34.2%. Girls were
      significantly more likely to consider themselves too fat (26% and 15%,
      respectively) and to report currently trying to lose weight (30% and 18%,
      respectively) compared to boys (P<0.05). CONCLUSIONS: The prevalence of
      overweight in Swiss children, and its attendant health and social consequences,
      are important public health concerns. SPONSORSHIP: The Swiss Foundation for
      Nutrition Research, Zurich, Switzerland.

PMID- 10918468
TI  - Low intakes of vegetables and fruits, especially citrus fruits, lead to
      inadequate vitamin C intakes among adults.
AB  - OBJECTIVE: To determine vitamin C intakes among adults and to identify
      differences in dietary intake associated with vitamin C consumption. DESIGN: This
      cross-sectional study compared vitamin C intake, nutrient intake, and food group
      choices of adults with low (<30 mg/d), marginal (30-60 mg/d), and desirable (>60
      mg/d) vitamin C intakes. SUBJECTS: Data from 2472 men and 2334 women aged 25-75 y
      were obtained from the 1994-1996 Continuing Survey of Food Intakes by Individuals
      (CSFII). RESULTS: Overall, 18% of the sample had low vitamin C intakes, 24% had
      marginal intakes, and 58% had desirable intakes. In addition to consuming less
      vitamin C, adults with low vitamin C intakes consumed significantly less
      (P</=0.001) energy-adjusted (ie nutrient/1000 kcal) folate, fiber, beta-carotene,
      and vitamin B6, and significantly more (P<0.001) fat. Compared to adults with low
      intakes, adults with desirable vitamin C intakes consumed significantly more
      (P</=0.001) high-vitamin C fruit juice and low-vitamin C vegetables, while
      consuming significantly less (P</=0.009) soft drinks, coffee/tea and alcoholic
      beverages. On average, adults with desirable vitamin C intakes consumed more than
      five daily servings of vegetables and fruits, of which more than one was citrus.
      Adults with low and marginal vitamin C intakes consumed less than one-fifth of a
      serving of citrus. CONCLUSIONS: A considerable number of adults under-consume
      vitamin C and total vegetables and fruits. Nutritionists should continue to
      promote five to nine daily servings of vegetables and fruits, at least one of
      which should be rich in vitamin C.

PMID- 10918469
TI  - Repeated measurements of energy intake, energy expenditure and energy balance in
      lactating Bangladeshi mothers.
AB  - OBJECTIVE: To examine changes in energetic parameters and nutritional status of
      chronically malnourished lactating women over a period of 13 months postpartum.
      DESIGN: A study of 15 lactating Bangladeshi mothers, of whom eight were tea
      pluckers and seven housewives, was conducted over a 13 months period from the
      birth of the child. Anthropometric measurements and body composition were
      determined on five occasions (at 3.5, 5.5, 7.5, 10 and 13 months) and energy
      expenditure (heart rate monitoring method), and energy intake (3-day weighing) on
      three occasions at 3.5, 10 and 13 months. RESULTS: The mothers, all of whom were
      of low BMI (range 14.9-18.1 kg/m2 at the end of the study) undertook high levels
      of physical activity (pluckers more so than housewives). There was evidence of
      weight loss over the 13 months, particularly between the fourth and sixth months
      postpartum, mainly due to a significant decrease in fat-free mass. Food intake
      and expenditure were higher in pluckers than housewives but energy balance was
      not significantly different, although workers were, on average, in negative
      balance on all three occasions. Food intake was based on cereals and fat
      deficient. CONCLUSIONS: A Bangladeshi sample of breast-feeding mothers studied
      over 13 months postpartum showed evidence of chronic malnutrition with women
      living on very low fat diets. All mothers, either housewives or tea pluckers were
      involved in energy demanding activities. There was a general tendency towards
      negative energy balance. Mothers lost weight, mainly fat-free mass over the study
      period.

PMID- 10918470
TI  - Moderate consumption of beer, red wine and spirits has counteracting effects on
      plasma antioxidants in middle-aged men.
AB  - OBJECTIVE: To evaluate the in vivo effects of moderate consumption of red wine,
      beer and spirits on antioxidants, antioxidant enzymes and antioxidant capacity.
      DESIGN: Randomized, diet-controlled, cross-over study. SUBJECTS: Twelve
      apparently healthy, non-smoking middle-aged men were included; 11 of them
      completed the study. INTERVENTIONS: Each subject consumed four glasses of red
      wine, beer, spirits and water (negative control) with evening dinner during four
      successive periods of 3 weeks, daily at the Institute. The total diet was
      supplied to the subjects and had essential the same composition during these 12
      weeks. RESULTS: Neither the enzyme activities of serum glutathion peroxidase,
      erythrocyte glutathion reductase and superoxide dismutase nor the plasma
      concentrations of alpha- and gamma-tocopherol, lutein, zeaxantin, beta
      cryptoxanthin, lycopene and alpha-carotene were affected. Plasma beta-carotene
      concentrations were decreased after 3 weeks' consumption of red wine, beer and
      spirits (40 g alcohol/day) as compared to consumption of water, by 15%
      (P=0.0005), 11% (P=0.010) and 13% (P=0.003), respectively. Also, plasma ascorbic
      acid was decreased after beer (15%, P=0.004) and spirits (12%, P=0.030), but not
      after wine consumption. Serum uric acid concentrations were increased after
      consumption of beer (15%, P<0.0001), spirits (8%, P=0.008) and red wine (9%,
      P=0.003). The overall serum antioxidant capacity, assessed as Trolox equivalent
      antioxidant capacity (TEAC), was similar for all treatments. CONCLUSIONS:
      Moderate consumption of red wine, beer and spirits has counteracting effects on
      plasma antioxidant components, resulting in no significant effect on overall
      antioxidant status. The effects on antioxidant parameters are largely independent
      of the type of alcoholic beverage, and probably irrelevant to chronic disease
      risk. SPONSORSHIP: Dutch Foundation for Alcohol Research (SAR).

PMID- 10918471
TI  - The relative validity of a computerized food frequency questionnaire for
      estimating intake of dietary iron and its absorption modifiers.
AB  - OBJECTIVE: To determine the relative validity of an iron food frequency
      questionnaire (iron FFQ) designed to assess intakes of dietary iron and its
      absorption modifiers. DESIGN: A computer-administered food frequency
      questionnaire was designed to estimate intake of total, non-haem, haem and meat
      iron as well as dietary components which influence iron absorption (vitamin C,
      phytate, calcium, grammes of meat/fish/poultry, tea and coffee) in women
      consuming a Western diet. The relative validity of the iron FFQ was assessed by
      comparing its results with those from weighed diet records collected over 11
      days. SETTING: Dunedin, New Zealand. PARTICIPANTS: Forty-nine women aged 19-31 y
      attending the University of Otago. RESULTS: There was good agreement between the
      iron FFQ and the weighed diet records for median intakes of total iron, non-haem
      iron, calcium, tea and coffee. For dietary component intakes, correlations
      between the two methods ranged from 0.39 (for vitamin C) to 0.87 (for coffee)
      with 0.52 for total iron, and 0.61 for haem iron. In cross-classification with
      the weighed diet record, the iron FFQ correctly classified between 22% (for
      vitamin C) and 51% (for phytate) of participants into the same quartile. Actual
      values for surrogate categories indicated that the questionnaire can clearly
      differentiate between low and high intakes of all the dietary components
      assessed. The questionnaire also showed an acceptable level of agreement between
      repeat administrations (eg a correlation for total iron of 0.65). CONCLUSIONS:
      The iron FFQ is appropriate for assessing group intakes of total iron, and iron
      absorption modifiers, in population studies to assess the aetiology and treatment
      of iron deficiency states in adult women consuming a Western diet. SPONSORSHIP:
      This research was supported (in part) by a grant from the Health Research Council
      of New Zealand.

PMID- 10918472
TI  - Early nutrition, essential fatty acid status and visual acuity of term infants at
      7 months of age.

PMID- 10918473
TI  - Radiation to control gene expression.

PMID- 10918474
TI  - Cytokine gene therapy of autoimmune demyelination revisited using herpes simplex
      virus type-1-derived vectors.
AB  - The peripheral delivery of drugs in patients affected by central nervous system
      (CNS)-confined diseases is therapeutically ineffective due to the presence of the
      blood-brain barrier which forms an inaccessible wall to the majority of CNS
      targeting molecules. When molecules with an anti-inflammatory profile have been
      systemically administered to patients affected by a chronic inflammatory
      demyelinating disease of the CNS, such as multiple sclerosis (MS), results have
      been disappointing. A successful therapeutic approach in MS should therefore
      consider the delivery of anti-inflammatory molecules directly into the CNS in
      order to inhibit blood-borne CNS-confined mononuclear cells which act as ultimate
      effector cells directly destroying oligodendrocytes and/or releasing myelinotoxic
      substances. Biological and physical vectors engineered with heterologous genes
      coding for immunomodulatory cytokines with an anti-inflammatory profile might
      represent the appropriate tool to deliver therapeutic genes into the CNS of
      patients with MS. So far, cytokine gene therapy has never been attempted in MS,
      but encouraging results have been obtained in the animal model of MS,
      experimental autoimmune encephalomyelitis (EAE), using viral vectors or plasmids
      engineered with cytokine genes and then injected systemically, either in the
      blood stream or circulating encephalitogenic T cells, or into the CNS. Here, we
      critically discuss the various attempts made in EAE using gene therapy protocols
      based on the delivery of immunomodulatory cytokine genes. Special emphasis is put
      on the use of non-replicative herpes simplex type-1 (HSV)-derived vectors
      engineered with the gene of the immunomodulatory cytokine interleukin (IL)-4.

PMID- 10918475
TI  - Sustained ex vivo and in vivo transfer of a reporter gene using polyoma virus
      pseudocapsids.
AB  - Properties of a virus-like artificial gene delivery vehicle, synthesised from
      recombinant major coat protein of mouse polyoma virus, have been explored. The
      protein, VP1, self assembles into protein spheres, or 'pseudocapsids, which can
      bind and transfer DNA into cells in vitro and in vivo. Here, the ability of
      pseudocapsids to carry DNA into a complex cell system (ex vivo organ cultures of
      rabbit cornea) or whole animals (mice) has been assessed. Evidence from
      histochemical and PCR experiments indicate that pseudocapsids stimulate uptake
      and stable maintenance of marker DNA in nondividing corneal cells as efficiently
      as a recombinant adenovirus. In athymic and immunocompetent mice, gene
      transmission occurs with no apparent adverse effects on the animals. In the
      presence of pseudocapsids, the marker gene was transferred to a range of organs,
      including the brains of animals, following peripheral or intranasal
      administration. In immunocompetent mice, significant long-term transcriptional
      expression (at least 22 weeks) was observed with pseudocapsids, a period
      significantly longer than observed with DNA alone (several weeks only), again
      with no obvious adverse effects. This study demonstrates that pseudocapsids from
      the murine virus, polyoma, constitute a novel transfer agent for long-term gene
      therapeutic applications in tissues or whole animals.

PMID- 10918476
TI  - Growth factor enhanced retroviral gene transfer to the adult central nervous
      system.
AB  - The use of viral vectors for gene delivery into mammalian cells provides a new
      approach in the treatment of many human diseases. The first viral vector approved
      for human clinical trials was murine leukemia virus (MLV), which remains the most
      commonly used vector in clinical trials to date. However, the application of MLV
      vectors is limited since MLV requires cells to be actively dividing in order for
      transduction and therefore gene delivery to occur. This limitation precludes the
      use of MLV for delivering genes to the adult CNS, where very little cell division
      is occurring. However, we speculated that this inherent limitation of ML V may be
      overcome by utilizing the known mitogenic effect of growth factors on cells of
      the CNS. Specifically, an in vivo application of growth factor to the adult
      brain, if able to induce cell division, could enhance MLV-based gene transfer to
      the adult brain. We now show that an exogenous application of basic fibroblast
      growth factor induces cell division in vivo. Under these conditions, where cells
      of the adult brain are stimulated to divide, MLV-based gene transfer is
      significantly enhanced. This novel approach precludes any vector modifications
      and provides a simple and effective way of delivering genes to cells of the adult
      brain utilizing MLV-based retroviral vectors.

PMID- 10918477
TI  - Murine dendritic cells infected with adenovirus vectors show signs of activation.
AB  - Dendritic cells (DC) are highly efficient antigen presenting cells being actively
      evaluated as vaccine components. A number of studies have shown adenovirus
      mediated gene transfer to cultured DCs is feasible and that Ad-modified DCs are
      effective at inducing T cell immunity in vitro and establishing antitumor
      immunity in experimental tumor models in vivo. The current study evaluates the
      biologic effects of Ad infection on murine bone marrow-derived DCs (BMDC) in
      primary culture. Ad infection (MOI 200) of BMDC induced significant increases in
      IL 12 p40 protein in culture supernatants (6 x that of uninfected BMDC and
      similar to that observed with addition of LPS and CD40 crosslinking antibody).
      Supernatants from Ad infected BMDCs induced appreciable increases in IFNgamma
      from naive splenocytes in culture. Consistent with DC activation, FACs analysis
      showed BMDC infected with Ad vectors up-regulated the surface expression of B7-2,
      ICAM-1 and MHC II. Additional experiments evaluated the role of virus attachment,
      internalization and gene expression using IL-12 p40 production as a marker of DC
      activation. Neither heat-inactivated Ad nor peptides containing the RGD sequence
      (the primary component of Ad penton base which interacts with cell surface
      integrins) induced significant amounts of IL12 p40. In contrast, psoralen/UV
      inactivated Ad showed similar levels of IL12 p40 production compared with intact
      Ad. These data suggest this phenomenon is dependent on viral entry into the cell
      and/or translocation to the nucleus, and is independent of either viral gene or
      transgene expression.

PMID- 10918478
TI  - A radiation-controlled molecular switch for use in gene therapy of cancer.
AB  - Ionising radiation induces the expression of a number of radiation-responsive
      genes and there is current interest in exploiting this to regulate the expression
      of exogenous therapeutic genes in gene therapy strategies for cancer. However,
      the radiation-responsive promoters used in these approaches are often associated
      with low and transient levels of therapeutic gene expression. We describe here a
      novel radiation-triggered molecular switching device based on promoter elements
      from the radiation-responsive Egr-1 gene and the cre-LoxP site-specific
      recombination system of the P1 bacteriophage. Using this system, a single,
      minimally toxic dose of radiation induced cre-mediated excision of a lox-P
      flanked stop cassette in a silenced expression vector and this resulted in
      amplified levels of CMV-promoter-driven expression of the exogenous tumour
      sensitising gene, HSV-tk. This strategy could be used in combination with
      targeted delivery and tumour-specific promoters to elicit the tumour-targeted and
      prolonged expression of a variety of tumour-sensitising genes and provide an
      unprecedented level of control and tumour selectivity.

PMID- 10918480
TI  - Particle-mediated gene transfer into murine livers using a newly developed gene
      gun.
AB  - Although particle-mediated gene transfer using gene gun technology has been
      applied for gene transfer into epidermis, applications of this technology to
      visceral tissues have not been well investigated. Although all helium gas-driven
      gene gun instruments have used macrocarriers to discharge DNA-coated
      microprojectiles so far, we used a newly developed gene gun instrument, in which
      a hammering bullet is used to discharge microprojectiles. With the gene gun, gold
      particles coated with lacZ expression plasmid were discharged to murine livers.
      LacZ expression was induced much more profoundly in the liver by particle
      mediated gene transfer than by simple plasmid injection and electroporation
      mediated gene transfer. LacZ expression was broadly and randomly distributed
      throughout the bombarded livers, indicating that particle-mediated gene transfer
      can induce transgene expression even at relatively distant areas from the surface
      of the bombarded tissue. Furthermore, although transgene expression was at its
      peak on day 2 after the bombardment, it was still detectable even on day 28.
      These results indicate that particle-mediated gene transfer with a newly
      developed gene gun may provide a new approach to gene therapy for human diseases.

PMID- 10918479
TI  - Modification of vascular tone using iNOS under the control of a radiation
      inducible promoter.
AB  - It may be therapeutically advantageous to alter tumour blood supply specifically.
      Nitric oxide is a potent vasodilator which is produced in many tissues by the
      enzyme nitric oxide synthase (NOS). We have transfected cDNA for the inducible
      isoform of this enzyme (iNOS), under the control of the radiation-inducible
      promoter WAF1. The activity of the promoter was initially assessed using green
      fluorescent protein (GFP) in both endothelial cells and rat tail artery segments.
      Induction of protein expression by 9.5- and 4.5-fold respectively, was observed
      after a radiation dose of 4 Gy. Artery sections were then transfected with the
      WAF1/iNOS construct; this gave five-fold induction of iNOS protein after a dose
      of 4 Gy. The transfected artery was also tested functionally for relaxation,
      indicative of NO production. One hour after exposure to 4 Gy there was a
      significant (65%) relaxation of artery segments that had been preconstricted with
      phenylephrine. This could be partially reversed by the NOS inhibitor nitro-L
      arginine. This study demonstrates that we can regulate vascular tone using an X
      ray inducible promoter.

PMID- 10918481
TI  - Intra-pinna anti-tumor vaccination with self-replicating infectious RNA or with
      DNA encoding a model tumor antigen and a cytokine.
AB  - To optimize polynucleotide vaccinations for protective antitumor immunity we used
      a self-replicating RNA vaccine in which Semliki Forest virus replicase drives RNA
      expression of the lacZ gene coding for beta-galactosidase as model tumor
      associated antigen (TAA). This was compared with replicase-deficient control RNA
      and with lacZ DNA plasmids with respect to gene expression in vitro and in vivo
      and for vaccination using the mouse ear pinna as an optimal immunization site. In
      vitro, the highest expression was observed with self-replicating RNA. Gene
      expression following pinna inoculation of either non-replicating DNA plasmids or
      self-replicating RNA was similar, lasting for 2-3 weeks. Higher antibody
      responses were obtained with RNA than with DNA. beta-Gal peptide specific CTL
      memory responses to lacZ DNA or RNA lasted for more than 6 weeks while respective
      responses induced by lacZ-transfected tumor cells lasted for only 2 weeks. To
      achieve a protective response against lacZ tumor cells with self-replicating RNA
      about a 100-fold lower dose of polynucleotide was sufficient in comparison to
      DNA. The extent of protective antitumor immunity not only depended on the gene
      dose used for vaccination, but also on the aggressiveness of the lacZ-transfected
      tumor line used for challenge. In comparison to lacZ-transfected tumor cells as
      vaccines, polynucleotide vaccination also demonstrated superiority with regard to
      cross-protection. Protective antitumor immunity could be strongly increased upon
      co-inoculation of lacZ DNA with IL-2 DNA or IL-12 RNA. IL-2 DNA, but not IL-12
      RNA, also augmented the CTL response while IL-12 RNA, but not IL-2 DNA, reduced
      the antibody response. These results demonstrate efficient protective antitumor
      immunity after intra-pinna lacZ TAA polynucleotide vaccination and show
      additional immunomodulatory effects by co-administration of cytokine
      polynucleotides.

PMID- 10918482
TI  - Polycation liposomes, a novel nonviral gene transfer system, constructed from
      cetylated polyethylenimine.
AB  - A novel gene transfer system was developed by using liposomes modified with
      cetylated polyethylenimine (PEI, MW 600). This polycation liposome, PCL, showed
      remarkable transfection efficiency as monitored by the expression of the GFP
      reporter gene. Most conventional cationic liposomes require
      phosphatidylethanolamine or cholesterol as a component, although PCLs did not.
      Egg yolk phosphatidylcholine- and dipalmitoylphosphatidylcholine-based PCL were
      as effective as dioleoylphosphatidylethanolamine-based PCLs for gene transfer.
      Concerning the cytotoxicity against COS-1 cells and hemolytic activity, the PCL
      was superior to conventional cationic liposome preparations. Furthermore, the
      transfection efficacy of PCLs was enhanced, instead of being diminished, in the
      presence of serum. Effective gene transfer was observed in all eight malignant
      and two normal cells line tested, as well as in COS-1 cells. We also examined the
      effect of the molecular weight of PEI on PCL-mediated gene transfer, and observed
      that PEI with a MW of 1800 Da was as effective as that with one of 600, but that
      PEI of 25,000 was far less effective. Finally, an in vivo study was done in which
      GFP was effectively expressed in mouse liver after injection of PCL via the
      portal vein. Thus, PCL represents a new system useful for transfection and gene
      therapy.

PMID- 10918483
TI  - Repeat administration of DNA/liposomes to the nasal epithelium of patients with
      cystic fibrosis.
AB  - The major cause of mortality in patients with cystic fibrosis (CF) is lung
      disease. Expression of the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene product in the airways is a potential treatment. Clinical studies in
      which the CFTR cDNA was delivered to the respiratory epithelia of CF patients
      have resulted in modest, transient gene expression. It seems likely that repeated
      administration of the gene transfer vector will be required for long-term gene
      expression. We have undertaken a double-blinded study in which multiple doses of
      a DNA/liposome formulation were delivered to the nasal epithelium of CF patients.
      Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC
      Chol/DOPE cationic liposomes, whilst two subjects received placebo. Each subject
      received three doses, administered 4 weeks apart. There was no evidence of
      inflammation, toxicity or an immune response towards the DNA/liposomes or the
      expressed CFTR. Nasal epithelial cells were collected 4 days after each dose for
      a series of efficacy assays including quantitation of vector-specific DNA and
      mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of
      halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated
      nasal potential difference (PD) measurements. On average, six of the treated
      subjects were positive for CFTR gene transfer after each dose. All subjects
      positive for CFTR function were also positive for plasmid DNA, plasmid-derived
      mRNA and CFTR protein. The efficacy measures suggest that unlike high doses of
      recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered
      without apparent loss of efficacy.

PMID- 10918484
TI  - Feeding dendritic cells with tumor antigens: self-service buffet or a la carte?
AB  - Adoptive transfer of autologous dendritic cells (DC) presenting tumor-associated
      antigens initiate and sustain an immune response which eradicate murine
      malignancies. Based on these observations, several clinical trials are in
      progress testing safety and efficacy with encouraging preliminary reports. In
      these approaches, ex vivo incubation of DC with a source of tumor antigens is
      required to load the relevant antigenic epitopes on the adequate antigen
      presenting molecules. Recent data show that in some instances exogenous DC
      artificially injected into malignant tissue or endogenous DC attracted to the
      tumor nodule by means of gene transfer of GM-CSF and CD40L into malignant cells
      result in efficacious antitumor immunity. In the case of intratumoral injection
      of DC the procedure is curative only if DC had been genetically engineered to
      produce IL-12, IL-6 or to express CD40L. Evidence has been obtained showing that
      intratumoral DC can capture and process tumor antigens to be presented to T
      lymphocytes. Although the exact mechanisms of tumor antigen acquisition by DC are
      still unclear, available data suggest a role for heat shock proteins released
      from dying malignant cells and for the internalization of tumor-derived apoptotic
      bodies. Roles for tumor necrosis versus apoptosis are discussed in light of the
      'danger theory'. Gene Therapy (2000) 7, 1167-1170.

PMID- 10918485
TI  - Sodium phosphate enhances plasmid DNA expression in vivo.
AB  - Intramuscular injection of plasmid DNA results in myofiber cell expression of
      proteins encoded by the DNA. The preferred vehicle for plasmid DNA injections has
      been saline (154 mM sodium chloride) or PBS (154 mM NaCl plus 10 mM sodium
      phosphate). Here, it is shown that injection of luciferase or beta-galactosidase
      encoding plasmid DNA in a 150 mM sodium phosphate vehicle into murine muscle
      resulted in a two- to seven-fold increase in transgene expression compared with
      DNA injected in saline or PBS. When the DNA encoded secreted alkaline
      phosphatase, preproinsulin or interferon, sodium phosphate vehicle increased
      their serum levels by two- to four-fold. When the DNA encoded mouse
      erythropoietin, sodium phosphate vehicle increased hematocrits by two-fold
      compared with DNA injected in saline. When the DNA encoded influenza
      nucleoprotein, sodium phosphate increased anti-nucleoprotein antibody titers by
      two-fold. The expression of luciferase from plasmid DNA instilled into lung was
      increased five-fold compared with that in vehicle without sodium phosphate.
      Incubation of plasmid DNA with muscle extract or serum showed that sodium
      phosphate protected the DNA from degradation. Thus, a change from sodium chloride
      to sodium phosphate vehicle can enhance the expression of plasmid DNA in a
      tissue, possibly by inhibiting DNA degradation. Gene Therapy (2000) 7, 1171-1182.

PMID- 10918486
TI  - Protective copolymers for nonviral gene vectors: synthesis, vector
      characterization and application in gene delivery.
AB  - Uncontrolled interactions of gene vectors and drug carriers in and with an in
      vivo environment pose serious limitations to their applicability. In order to
      reduce such interactions we have designed, synthesized and applied novel
      copolymers of poly(ethylene glycol) and reactive linkers which are derivatized
      with anionic peptides after copolymerization. The anionic copolymer derivatives
      are used to coat positively charged nonviral gene vectors by electrostatic
      interactions. The copolymer coat confers to polyelectrolyte colloids of DNA and
      polycations steric stabilization in their minimal size and prevents salt- and
      serum albumin-induced aggregation. Furthermore, complement activation and the
      interaction with serum proteins are drastically reduced or abolished in contrast
      to unprotected DNA complexes. The designed vectors are compatible with the
      intracellular steps of gene delivery and can even enhance transfection efficiency
      as demonstrated with various adherent and nonadherent cell lines in culture. The
      synthetic concept is amenable to the principles of combinatorial chemistry and
      the copolymeric products may be applicable beyond gene delivery in targeted drug
      delivery. Gene Therapy (2000) 7, 1183-1192.

PMID- 10918488
TI  - Helper-dependent adenovirus vectors: their use as a gene delivery system to
      neurons.
AB  - Recombinant adenovirus vectors have provided a major advance in gene delivery
      systems for post-mitotic neurons. However, the use of these first generation
      vectors has been limited due to the onset of virally mediated effects on cellular
      function and viability. In the present study we have used primary cultures of
      cerebellar granule neurons to examine the efficacy and cytotoxic effects of a
      helper-dependent adenovirus vector (hdAd) in comparison with a first generation
      vector. Our results demonstrate that the hdAd system provides equally efficient
      infectivity with significantly reduced toxicity in comparison to first generation
      vectors. Neurons transduced with a high titre of a first generation vector
      exhibited a time-dependent shut down in global protein synthesis and impaired
      physiological function as demonstrated by a loss of glutamate receptor
      responsiveness. This was followed by an increase in the fraction of TUNEL
      positive cells and a loss of neuronal survival. In contrast, hdAds could be used
      at titres that transduce >85% of neurons with little cytotoxic effect: cellular
      glutamate receptor responses and rates of protein synthesis were
      indistinguishable from uninfected controls. Furthermore, cell viability was not
      significantly affected for at least 7 days after infection. At excessive viral
      titres, however, infection with hdAd did cause moderate but significant changes
      in cell function and viability in primary neuronal cultures. Thus, while these
      vectors are remarkably improved over first generation vectors, these also have
      limitations with respect to viral effects on cellular function and viability.
      Gene Therapy (2000) 7, 1200-1209.

PMID- 10918487
TI  - Long-term tracking of murine hematopoietic cells transduced with a bicistronic
      retrovirus containing CD24 and EGFP genes.
AB  - Hematopoietic stem cells (HSCs) are attractive targets for gene therapy, but
      current gene transfer methodologies are inadequate for efficient HSC transduction
      and perpetual transgene expression. To improve gene transfer vectors and
      transduction protocols, it is vital to establish a system to evaluate transgene
      expression and the long-term behavior of transduced cells in vivo. For this
      purpose, we constructed a bicistronic retrovirus encoding the human CD24 (as the
      first cistron) and the enhanced green fluorescent protein (EGFP; as the second
      cistron). Murine bone marrow cells were transduced with this vector and the
      transgene expression was monitored along with hematopoietic reconstitution.
      Stable expression of CD24 and EGFP was demonstrated in the long-term repopulating
      cells for at least 6 months, and multi-parameter flow cytometry illustrated
      expression of both markers in all the lymphohematopoietic lineages examined (B
      and T lymphoid, erythroid and myeloid). Sustained expression was also shown in
      the secondary transplants for 6 months, suggesting that self-renewing HSCs were
      transduced by this vector. Overall, EGFP-tagged bicistronic retroviruses would
      provide powerful tools for detailed in vivo analysis of transduced hematopoietic
      cells, such as transgene expression in conjunction with lineage differentiation.
      Gene Therapy (2000) 7, 1193-1199.

PMID- 10918489
TI  - Chronic lymphocytic leukemia B cells are highly sensitive to infection by herpes
      simplex virus-1 via herpesvirus-entry-mediator A.
AB  - We found that chronic lymphocytic leukemic (CLL) B cells are highly sensitive to
      infection with vectors derived from replication-defective herpes simplex virus-1
      (rdHSV-1). CLL B cells were found to express high levels of herpes virus entry
      mediator (Hve) A, but not HveC, the other known receptor for HSV-1. An HveA cDNA
      from CLL cells was found to encode Arg-->Lys and Val-->Iso substitutions at amino
      acids 17 and 241, respectively. Nevertheless, this cDNA encoded a functional
      receptor for HSV-1 when transfected into Chinese hamster ovarian (CHO) cells.
      Antibodies to HveA could block rdHSV-1 infection of CLL cells and HveA
      transfected CHO cells with similar efficiencies in vitro. In contrast to B cells
      of normal donors, CLL B cells were resistant to the cytopathic effects of
      infection by rdHSV-1 and maintained high-level expression of the transgene for
      several days in vitro. We propose that this is due to the expression by CLL cells
      of the anti-apoptotic protein, bcl-2. Consistent with this, we found that
      transduction of HeLa cells with a retrovirus expression vector encoding bcl-2
      rendered HeLa cells resistant to the cytopathic effects of rdHSV-1. HSV-1-derived
      vectors should be excellent vehicles for gene transfer into CLL B cells, allowing
      for its potential use in gene therapy for this disease. Gene Therapy (2000) 7,
      1210-1216.

PMID- 10918490
TI  - Complex interactions between the replicating oncolytic effect and the
      enzyme/prodrug effect of vaccinia-mediated tumor regression.
AB  - Replicating viruses for cancer gene therapy have beneficial antitumor effects,
      however, in the setting of an enzyme/prodrug system, the interactions between
      these viruses and the activated agents are complex. A replicating vaccinia virus
      expressing the cytosine deaminase gene (VVCD), which converts the prodrug 5-FC
      into 5-FU, was characterized in vitro and in vivo for its antitumor effects and
      pathogenicity. Replicating VVCD (+/-5-FC) at various MOIs was used to infect MC38
      murine colon adenocarcinoma cells. At high MOIs (>0.1) virus alone was able to
      kill the majority (65-90%) of cells by day 5 with no additional benefit from
      prodrug. At low MOIs only the effect of prodrug is seen. Cell lysates
      demonstrated 300-fold reduced viral recovery from cells treated with both VVCD
      and 5-FC compared with controls treated with virus alone. Nude mice bearing
      subcutaneous MC38 tumors were injected with VVCD (or control) and treated with
      5FC or control. Mice injected with VVCD (with or without 5FC treatment) had
      smaller tumors than the controls, suggesting that replicating vaccinia alone is
      cytotoxic to tumors in vivo. The addition of 5-FC improved the antitumor response
      when a low dose of virus was injected into tumors. Also, compared with mice that
      received virus alone, those that received VVCD and 5FC had significantly
      prolonged survival from virus-mediated death. In conclusion, the addition of an
      enzyme/prodrug system to a replicating virus can improve the antitumor response
      and decrease viral pathogenicity. Gene Therapy (2000) 7, 1217-1223.

PMID- 10918491
TI  - Modulation of the typical multidrug resistance phenotype by targeting the MED-1
      region of human MDR1 promoter.
AB  - Multidrug resistance of cancer (MDR) is the major cause of failure of
      chemotherapy. The typical MDR phenotype is due to the overexpression of membrane
      proteins among which the main representative is P-glycoprotein (Pgp) encoded by
      the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been
      unsuccessful in human therapy due to their intrinsic toxic effects. In an effort
      to modulate the MDR phenotype efficiently we designed an antisense and a
      transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter.
      The choice of the start point of transcription in a multiple start site window is
      related to an upstream MED-1 cis-element, the sequence and configuration of which
      are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A
      12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both
      containing the MED-1 sequence, were designed and efficiently vectorized into the
      nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP)
      and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to
      transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP
      cells decreased, and thus its production, and viability of CEM/VLB0.45 cells
      decreased by 63% in the presence of vinblastine, revealing that their resistance
      to the anticancer drug was reversed. These results open new insights into
      transcriptional decoy and anti-gene therapies of MDR cancers that overproduce
      Pgp. Gene Therapy (2000) 7, 1224-1233.

PMID- 10918492
TI  - Enhancement of cytosine arabinoside-induced apoptosis in human myeloblastic
      leukemia cells by NF-kappa B/Rel- specific decoy oligodeoxynucleotides.
AB  - The activity of NF-kappa B/Rel nuclear factors is known to inhibit apoptosis in
      various cell types. We investigated whether the subtraction of NF-kappa B/Rel
      activity influenced the response of 11 AML (M1, M2 and M4) patients' cells to
      AraC. To this end we used a phosphorothioate double-stranded decoy
      oligodeoxynucleotide (ODN) carrying the NF-kappa B/Rel- consensus sequence. Cell
      incubation with this ODN, but not its mutated (scrambled) form used as a control,
      resulted in abating the NF-kappa B/Rel nuclear levels in these cells, as verified
      by electrophoretic mobility shift assay (EMSA) of cells' nuclear extracts. We
      incubated the leukemic cells with AraC (32 or 1 microM), in either the absence or
      presence of the decoy or the scrambled ODN, and analyzed cell apoptosis. The
      spontaneous cell apoptosis detectable in the absence of AraC (<25%) was not
      modulated by the oligonucleotide presence in cell cultures. On the other hand, in
      10 of the 11 samples tested, the decoy kappa B, but not the scrambled ODN
      significantly (P < 0.01 in a Student's t test) enhanced cell apoptotic response
      to AraC. Such an effect was particularly remarkable at low AraC doses (1 microM).
      These findings indicate that NF-kappa B/Rel activity influences response to AraC
      in human primary myeloblastic cells, and suggests that the inhibition of NF-kappa
      B/Rel factors can improve the effect of chemotherapy in AML. Gene Therapy (2000)
      7, 1234-1237.

PMID- 10918493
TI  - Ischemia/reperfusion injury-mediated down-regulation of adenovirus-mediated gene
      expression in a rat heart transplantation model is inhibited by co-application of
      a TNFRp55-Ig chimeric construct.
AB  - E1-deleted adenoviral vectors are efficient vectors for somatic gene therapy.
      Recently, we have shown that intratracheal application of an adenoviral reporter
      construct leads to significant reporter gene expression in rat lungs within 24 h.
      In contrast, reporter gene expression in syngeneic rat heart transplants after
      adenovirus-mediated gene transfer was delayed. Since the adenovirus cannot
      replicate, down-regulation of the hCMV-IE promoter controlled reporter gene
      expression in initially infected cells by cytokines, which are released as a
      result of ischemia/reperfusion injury, might be involved. In order to investigate
      the role of proinflammatory cytokines, eg TNF-alpha in affecting hCMV-IE promoter
      driven reporter gene expression, transient blockade of TNF-alpha was achieved by
      local co-application of an Ad-construct encoding for a soluble TNFRp55-Ig
      chimeric molecule in a syngeneic rat heart transplantation model. Co-application
      of the reporter construct together with the TNFRp55-Ig chimeric molecule
      significantly increased the early reporter gene expression after transplantation.
      Moreover, infiltration of inflammatory cells (T cells, macrophages, NK cells) and
      production of TNF-alpha in the transplant was markedly reduced. Our results
      indicate that: (1) proinflammatory cytokines are involved in down-regulation of
      reporter gene expression in ischemia/reperfusion injured tissues; and (2)
      inhibition of TNF-alpha might be a useful tool to increase early gene expression
      in gene therapy protocols, particularly in transplantation. Gene Therapy (2000)
      7, 1238-1243.

PMID- 10918494
TI  - Adeno-associated virus vector-mediated bcl-2 gene transfer into post-ischemic
      gerbil brain in vivo: prospects for gene therapy of ischemia-induced neuronal
      death.
AB  - The proto-oncogene bcl-2 is known as an anti-apoptotic gene that confers the
      ability to block neuronal cell death after transient ischemia. In order to
      examine whether the bcl-2 gene can be used for protection of ischemic brain
      injury, we generated adeno-associated virus (AAV) vectors capable of expressing
      human bcl-2. Replication-defective AAV vectors were found effectively to transfer
      and express bcl-2 gene in the gerbil hippocampal neurons. Transduction with AAV
      bcl-2 5 days before forebrain ischemia prevented the DNA fragmentation in the CA1
      neurons that is commonly associated with ischemia-induced cell death.
      Furthermore, the application of AAV bcl-2 as late as 1 h following an ischemic
      insult also prevented DNA fragmentation in CA1 neurons. These results suggest
      that the bcl-2 protein has neuroprotective functions that inhibit ischemic cell
      death and demonstrate the potential of AAV bcl-2 for use in post-ischemic gene
      therapy in the brain. Gene Therapy (2000) 7, 1244-1249.

PMID- 10918495
TI  - Long-term expression and transfer of arylsulfatase A into brain of arylsulfatase
      A-deficient mice transplanted with bone marrow expressing the arylsulfatase A
      cDNA from a retroviral vector.
AB  - A deficiency of arylsulfatase A (ASA) results in the lysosomal lipid storage
      disease metachromatic leukodystrophy. The disease mainly affects the central
      nervous system causing a progressive demyelination. A therapeutic effect will
      depend on the delivery of the deficient enzyme to the central nervous system. We
      have transplanted ASA-deficient mice with bone marrow transduced with a
      retroviral vector expressing the human ASA cDNA. All transplanted animals
      initially showed high serum levels of human ASA. In 50% of the recipients high
      ASA serum levels were sustained for 12 months after transplantation. In the
      remaining mice, serum levels decreased rapidly to low or undetectable levels. ASA
      activity and immunoreactivity was detectable in all organs of animals with
      continuous levels of ASA in serum. Most notably, substantial amounts of ASA
      activity were transferred into the brain, reaching up to 33% of the normal tissue
      level. In contrast to peripheral organs, the amount of enzyme delivered to the
      brain did not correlate with ASA serum levels as an indicator of overexpression.
      This reveals that enzyme transfer to the brain is not due to endocytosis of serum
      ASA by endothelial cells, but rather to bone marrow-derived cells migrated into
      the brain. Gene Therapy (2000) 7, 1250-1257.

PMID- 10918496
TI  - Assessing gene expression in vivo: magnetic resonance imaging and spectroscopy.
AB  - Recent developments in magnetic resonance imaging and spectroscopy afford the
      possibility of detecting and assessing transfer, expression and subsequent
      therapeutic changes of effector or marker transgenes noninvasively. In the field
      of MR imaging, 'smart' MR contrast agents are being developed, so called because
      they change their conformational structure and in so doing induce MR detectable
      changes in a given tissue. These agents become 'switched on' in response to
      physiological changes brought about by the enzymatic action of a given gene
      product (enzymes), and are being developed for use in intact cells, isolated
      organs and animal models. Ultimately, these agents hold the promise of bridging
      the gap between the laboratory and the patient with noninvasive detection of
      transgene expression in vivo in man. Similarly, magnetic resonance spectroscopy
      is being developed as a noninvasive method to assess transgene expression
      indirectly by means of MR visible intracellular markers. These markers take the
      form of intracellular endo/exogenous metabolites associated with exogenous enzyme
      expression and function. Again, this technique will be applicable to a variety of
      different situations, from cell suspensions through to clinical imaging of the
      whole body. In this article the unique opportunities for laboratory-based and
      clinical studies afforded by MR techniques are discussed.

PMID- 10918497
TI  - Feasibility of CTLA4Ig gene delivery and expression in vivo using retrovirally
      transduced myeloid dendritic cells that induce alloantigen-specific T cell anergy
      in vitro.
AB  - Dendritic cells (DC) are highly specialised, bone marrow (BM)-derived antigen
      presenting cells (APC) that initiate and regulate immune responses. They provide
      costimulatory signals (in particular, CD40 and the CD28 ligands CD80 and CD86)
      necessary for naive T cell activation. Functional expression of CD80 and CD86 is
      blocked by the fusion protein cytotoxic T lymphocyte antigen 4-immunoglobulin
      (CTLA4Ig), that promotes tolerance induction in animals. Here, replicating mouse
      (B10; H2b) myeloid DC progenitors, were retrovirally transduced to express
      CTLA4Ig using the centrifugal enhancement method. Gene product was detected by
      immunocyto- or histochemistry. Maximal DC transduction efficiency was 62%.
      Compared with control, zeomycin-resistance gene (Zeo)-transduced DC, CTLA4Ig
      expressing cells showed markedly impaired capacity to stimulate naive allogeneic
      (C3H; H2k) T cell proliferation and cytotoxic T lymphocyte (CTL) generation.
      Their ability to induce alloantigen-specific T cell hyporesponsiveness was
      reversed by exogenous IL-2 in secondary mixed leukocyte reactions (MLR).
      Following local (s.c.) transfer to allogeneic recipients, the genetically
      modified DC trafficked to T cell areas of draining lymphoid tissue, where
      transgene expression was detected. Ex vivo analysis of proliferative and CTL
      responses revealed donor-specific inhibition of alloimmune reactivity by the
      CTLA4Ig-transduced DC. This effect was associated with marked inhibition of
      interferon (IFN)-gamma production, but significant augmentation of IL-4 and IL-10
      secretion. Thus, retroviral transduction of DC permits in vivo delivery of
      CTLA4Ig to the precise microenvironment where antigen (Ag) presentation occurs.
      Comparatively nonimmunogenic retroviral vectors, that allow permanent transgene
      expression in DC, and promote localized delivery of the immunosuppressive
      transgene product, promote immune deviation and Ag-specific T cell
      hyporesponsiveness.

PMID- 10918498
TI  - Baculovirus vectors repress phenobarbital-mediated gene induction and stimulate
      cytokine expression in primary cultures of rat hepatocytes.
AB  - Baculovirus transfection strategies have proven successful at transferring
      foreign DNA into hepatoma cells and primary hepatocytes. When testing the utility
      of these methodologies in cultured hepatocytes, we discovered that the presence
      of baculovirus disrupts the phenobarbital (PB) gene induction process, a potent
      transcriptional activation event characteristic of highly differentiated
      hepatocytes, and repressed expression of the albumin gene. In concert with
      previous reports from our laboratory demonstrating that increased cAMP levels can
      completely repress the induction of specific cytochrome P450 (CYP) genes, cAMP
      concentrations and PKA activities were measured in the primary hepatocytes
      subsequent to baculovirus exposure. However, neither parameter was affected by
      the presence of the virus. To evaluate whether immune response modulation was
      triggered by baculovirus exposure, RNase protection assays were performed and
      demonstrated that baculovirus infection activates TNF-alpha, IL-1alpha and IL
      1beta expression in the primary hepatocyte cultures. Immunocytochemical
      experiments indicated that the production of cytokines was likely due to the
      presence of small numbers of Kupffer cells present in the culture populations.
      Exogenously added TNF-alpha was also effective in repressing PB induction,
      consistent with other reports indicating that inflammatory cytokines are capable
      of suppressing expression of biotransformation enzyme systems. Comparative
      studies demonstrated the specificity of these effects since exposures of
      hepatocytes to adenoviral vectors did not result in down-regulation of hepatic
      gene responsiveness. These results indicate that baculovirus vectors enhance the
      expression of inflammatory cytokines in primary hepatocyte cultures, raising
      concerns as to whether these properties will compromise the use of baculovirus
      vectors for study of cytochrome P450 gene regulation, as well as for liver
      directed gene therapy in humans.

PMID- 10918499
TI  - Calcium phosphate precipitates augment adenovirus-mediated gene transfer to blood
      vessels in vitro and in vivo.
AB  - Adenovirus (Ad)-mediated gene transfer to blood vessels is relatively
      inefficient, probably because binding of adenovirus to the endothelium and
      adventitia seems to be limited. Association of calcium phosphate (CaPi)
      precipitates with adenovirus improves efficiency of gene transfer to some cells
      in culture and to mouse lung in vivo. In this study, we tested the hypothesis
      that CaPi is useful for adenovirus-mediated gene transfer to blood vessels. In
      fibroblast and endothelial cells in culture, Ad:CaPi coprecipitates greatly
      increased transgene expression. Ad:CaPi also enhanced transgene expression in
      both adventitia and endothelium of carotid arteries and aortae from rabbits
      studied ex vivo. After injection of Ad:CaPi into the cisterna magna of rabbits in
      vivo, the transgene product was markedly increased in leptomeninges of the
      ventral brain stem, including the adventitia of the basilar artery. We also
      examined mechanisms of enhanced gene transfer. Binding of adenovirus to
      fibroblast and endothelial cells in culture, and to the basilar artery in vivo,
      as determined using Southern blot analysis, was augmented by CaPi. Antibody to
      adenoviral fiber knob did not inhibit augmented transgene expression by Ad:CaPi.
      The finding suggests that improved adenoviral binding occurs primarily via a
      fiber-independent pathway. Thus, CaPi precipitates are useful for improvement of
      adenovirus-mediated gene transfer to blood vessels in vitro and in vivo.

PMID- 10918500
TI  - Disruption of integrin-dependent adhesion and survival of endothelial cells by
      recombinant adenovirus expressing isolated beta integrin cytoplasmic domains.
AB  - We explored the possibility of using a genetic approach to inhibit integrin
      mediated endothelial cell adhesion and survival. We constructed recombinant
      adenoviruses (Ads) expressing chimeric proteins consisting of the cytoplasmic and
      transmembrane domains of integrin beta1 (CH1), beta3 (CH3) or the beta1
      transmembrane domain alone (CH2) connected to the extracellular domain of L3T4
      placed under the control of the CMV promoter (AdCMV) or the endothelial cell
      specific Tie-1 promoter (AdTie). All constructs were expressed in a dose- and
      time-dependent manner with over 90% of cells expressing the constructs within 24
      h (AdCMVs) or 72 h (AdTies) after infection. Confluent monolayers of HUVEC
      infected with AdCMVCH1 or AdCMVCH3 detached from the substrate in a time- and
      dose-dependent manner with over 95% of the cells being detached 2 days (AdCMVs)
      or 3 to 4 days (AdTies) after infection. Cell detachment was preceded by the
      disruption of focal adhesions and reorganization of the actin cytoskeleton and
      was associated with a reduced ligand-binding activity of beta1, while cell
      surface density of beta1 integrins remained unchanged. Detached cells failed to
      re-adhere to different matrix proteins, without, however, any specificity toward
      beta1 or beta3 integrin-mediated adhesion. Upon detachment, HUVEC rapidly died by
      apoptosis. These results demonstrate that dominant negative inhibition of
      integrin function is an effective approach to disrupt endothelial cell adhesion
      and survival in vitro.

PMID- 10918501
TI  - Influence of promoter and WHV post-transcriptional regulatory element on AAV
      mediated transgene expression in the rat brain.
AB  - Recombinant adeno-associated viruses (rAAVs) can transduce several tissues,
      including the brain. However, in brain the duration of gene expression in
      different areas is variable, which has been ascribed to viral (CMV) promoter
      silencing in some regions over time. We have compared expression of enhanced
      green fluorescent protein (EGFP) in the nigrostriatal pathway of rats mediated by
      rAAVs containing the CMV or platelet-derived growth factor-beta chain (PDGF-beta)
      promoter. In addition, we studied the effects of the woodchuck hepatitis virus
      post-transcriptional regulatory element (WPRE) on transgene expression in vivo.
      The rAAV vectors containing the neuron-specific PDGF-beta chain promoter
      transduced significantly more dopaminergic neurons than titer-matched vectors
      carrying the CMV promoter. Moreover, the WPRE further increased EGFP expression,
      and a rAAV vector incorporating both the PDGF-beta chain promoter and the WPRE
      resulted in efficient EGFP expression in dopaminergic neurons and their
      projections in the striatum for at least 41 weeks after virus injection. Our
      results emphasize the importance of a strong tissue-specific promoter in
      achieving optimal transgene expression, not only in long-term but also in short
      term studies where viral titers may be limiting. Furthermore, they suggest that
      incorporation of the WPRE into rAAVs, and possibly other types of vectors, is
      useful to enhance transgene expression in vivo.

PMID- 10918502
TI  - Gene transfer of GM-CSF, CD80 and CD154 cDNA enhances survival in a murine model
      of acute leukemia with persistence of a minimal residual disease.
AB  - Gene transfer of various cytokines and co-stimulatory molecules has been reported
      to induce a potent antileukemic immunity in murine models, however, the relative
      efficiency and possible synergistic effects between candidate genes have not been
      extensively investigated. We analyzed in a murine model of BCR/ABL acute leukemia
      whether gene transfer of CD154, CD80 or GM-CSF as a single agent or combination
      of CD154 + GM-CSF, CD80 + CD154 and GM-CSF + CD80 in leukemic cells could enhance
      survival. We observed that CD154 gene transfer induced a marked inhibition of
      leukemogenicity, and also that CD154 and combination of GM-CSF and CD80 gene
      transfer protected mice against subsequent challenge with leukemic cells and had
      a therapeutic effect for a pre-established leukemia disease. We also found
      minimal residual leukemic disease by RT-PCR for 6 to 12 months in 0 to 25% of
      animals injected with transduced leukemic cells and surviving the challenge
      without evidence of disease, except in the control empty plasmid group where very
      few mice survived the challenge but all of those were positive by RT-PCR. These
      findings suggest that leukemic cell vaccination by gene transfer can induce a
      tumor dormancy phenomenon compatible with long-term survival.

PMID- 10918503
TI  - Improved safety through tamoxifen-regulated induction of cytotoxic genes
      delivered by Ad vectors for cancer gene therapy.
AB  - The transfer of pro-apoptotic genes to tumors is one of the most promising
      strategies for anticancer gene therapy. However, the use of potentially toxic
      genes, such as tumor suppressor genes or apoptotic genes, needs controllable
      transgene activation. To achieve regulation of the transgene at a desired time,
      we developed an adenovirus (Ad) vector, in which the apoptotic activity of the
      target gene has been made 4-OHT-dependent by fusion to the ligand binding-domain
      of the estrogen receptor (ER). For evaluation of the system in human tumor cells,
      we used the E2F1 gene which encodes a transcription factor that triggers massive
      apoptosis in several human cancers. AdER-E2F1 expressed high levels of transgene
      over at least 1 week. Upon activation of E2F1 by the ligand 4-hydroxy-tamoxifen
      (4-OHT) the ER-E2F1 fusion protein correctly translocated from the cytosol to the
      nucleus, transactivated E2F-dependent promoters, and rapidly induced substantial
      E2F1-related toxicity. Finally, experiments in nude mice showed tightly regulated
      tumor growth suppression in vivo. Taken together, our system represents a
      powerful approach for tight regulation and rapid induction of cytotoxicity as the
      major criteria for safe gene delivery.

PMID- 10918504
TI  - Transcription factor decoy for NFkappaB inhibits TNF-alpha-induced cytokine and
      adhesion molecule expression in vivo.
AB  - The expression of several cytokines and adhesion molecules is regulated by the
      transcription factor NFkappaB, which is activated by tumor necrosis factor alpha
      (TNF-alpha). In this study, we employed a mouse model of nephritis induced by TNF
      alpha to examine whether inhibition of NFkappaB activity using transcription
      factor decoy oligonucleotides (ODN) blocks cytokine and adhesion molecule
      expression and attenuates the renal inflammatory response. First, we developed a
      method for delivering FITC-ODN in vivo into mouse kidney glomeruli by employing
      HVJ-liposome. Then, in order to study the feasibility of decoy strategy in vivo,
      the reporter gene chloramphenicol acetyltransferase (CAT) driven by three
      tandemly repeated NFkappaB binding sequences was transfected into the kidney.
      Intrapenetorial injection of TNF-alpha stimulated CAT expression in vivo, and the
      increase in CAT expression was completely abolished by NFkappaB decoy ODN, but
      not scrambled ODN. Therefore, we examined the effect of NFkappaB decoy ODN
      transfection on TNF-alpha-induced endogenous interleukin (IL)-1alpha, IL-1beta,
      IL-6, ICAM-1 and VCAM-1 gene expression as assessed by RT-PCR and Northern
      blotting. Our present data showed that NFkappaB decoy, but not scrambled, ODN
      abolished TNF-alpha induced gene expression in vivo, as well as glomerular
      inflammation as assessed by CD45 staining. Taken together, our results suggest
      the potential utility of NFkappaB decoy strategy for molecular therapy to
      glomerular inflammatory diseases.

PMID- 10918505
TI  - Haemoglobin interferes with the ex vivo luciferase luminescence assay:
      consequence for detection of luciferase reporter gene expression in vivo.
AB  - The luciferase reporter gene is a useful tool for determining the efficacy of
      transfection of plasmid DNA and adenovirus-mediated gene transfer in vivo.
      However, we report here that the haemoglobin present in tissue samples can mask
      the detection of the luciferase activity and lead to underestimation of the
      luciferase levels. We evaluated the degree of interference in different organ
      samples of mice and investigated the possibilities for removal of haemoglobin
      from tissue samples by: (1) perfusion of the whole animal; (2) different
      hypotonic treatments lysing preferentially red blood cells; and (3)
      chromatographic separation. Removal of haemoglobin resulted in significantly
      improved detection of luciferase activity from tissue samples. The results
      indicate that the luciferase activity determined in tissue samples may not
      reflect the actual level of reporter gene expression, if contaminating blood is
      not taken into consideration.

PMID- 10918506
TI  - A versatile system for receptor-mediated gene delivery permits increased entry of
      DNA into target cells, enhanced delivery to the nucleus and elevated rates of
      transgene expression.
AB  - We have developed a method for stabilisation of polyelectrolyte gene delivery
      vectors by crosslinking their surfaces with biodegradable multivalent copolymers
      based on N-(2-hydroxypropyl)methacrylamide (HPMA). The resulting nanoparticulate
      vectors resist attack by serum proteins and can be modified for cell-specific
      delivery by incorporation of targeting ligands onto the polymer coating. Here we
      show that vascular endothelial growth factor (VEGF), transferrin and basic
      fibroblast growth factor (bFGF) can each be linked to polyHPMA-coated poly(L
      lysine)/DNA complexes. All ligand-targeted complexes demonstrated increased
      uptake into receptor-positive cells (measured using plasmids containing 32P
      dCTP), that could be antagonised with excess free ligand. Targeted complexes also
      showed increased transfection, resistant to inhibition by serum, suggesting the
      possibility of effective application in vivo. Analysis using fluorescence
      microscopy confirmed enhanced uptake of ligand-targeted complexes (using Texas
      Red-labelled plasmid DNA), although VEGF- and transferrin-targeted complexes were
      restricted to cytoplasmic or perinuclear distributions. In contrast, bFGF
      targeted complexes showed efficient delivery into the nucleus, with accumulation
      of more than 100000 plasmids per cell within distinct intranuclear compartments.
      This method permits versatile targeting of genes to selected cells and may also
      permit manipulation of intracellular trafficking. It should find several
      important applications in gene delivery systems both in vitro and in vivo.

PMID- 10918507
TI  - Long-term expression of human alpha1-antitrypsin gene in mouse liver achieved by
      intravenous administration of plasmid DNA using a hydrodynamics-based procedure.
AB  - The liver is an important target organ for gene transfer due to its large
      capacity for synthesizing serum proteins and its involvement in numerous genetic
      and acquired diseases. Previously, we and others have shown that an efficient
      gene transfer to liver cells in vivo can be achieved by an intravenous injection
      of plasmid DNA using a hydrodynamics-based procedure. In this study, we
      systematically characterized the expression of transgene encoding a secretory
      protein in mouse. Using human alpha1-antitrypsin (hAAT) gene as a reporter, we
      demonstrate that the serum level of hAAT can reach as high as 0.5 mg/ml by a
      simple tail vein injection of 10-50 microg plasmid DNA into a mouse. The serum
      hAAT reaches the peak level 1 day after DNA injection and then declines during
      the following 2 to 4 weeks to 2-5 microg/ml, a level which persists for at least
      6 months. Southern analysis of extracted DNA and RT-PCR analysis of RNA from the
      liver reveal that hAAT gene is active and present as episomal form after 6
      months. These results suggest that the hydrodynamics-based transfection procedure
      provides a valuable tool for screening genes for therapeutic purposes in whole
      animals.

PMID- 10918508
TI  - Safety evaluation of immunomodulatory biopharmaceuticals: can we improve the
      predictive value of preclinical studies?

PMID- 10918509
TI  - Overview status of preclinical safety assessment for immunomodulatory
      biopharmaceuticals.
AB  - Scientists from academia, industry, FDA, European and Japanese regulatory groups
      met to discuss key considerations that are central to the safe and expeditious
      development of novel biologic agents that are thought to act by modulation of the
      host immune system. In the presentations and case studies, particular attention
      was given to the current clinical experience with immunosuppressant agents. Many
      new biologic agents (such as humanized monoclonal antibodies) have been developed
      to interact in a highly specific manner with their target. However, their
      pharmacologic properties may be more complex than originally appreciated,
      impacting on clinical trial designs. The goal of preclinical safety assessment
      should be to provide some assurance that patients will be protected from any
      unacceptable risks by defining "safe" and "active" doses. For immunomodulatory
      molecules, particular attention is paid to defining potential for increased risks
      of lymphoproliferative disorders, opportunistic infections, and immune
      impairment. To address these issues, a wide variety of preclinical studies,
      mainly in non-human primates, have been performed for the purpose of assessing
      the potential risk of drug-induced, human immunotoxicity. Case studies presented
      at this symposium showed the feasibility of assessing humoral and cell-mediated
      aspects of the immune system, using antigen and neoantigen challenges,
      immunohistochemical, and flow cytometric (FACS) methods. In some cases,
      homologous forms of the biologic agent and "humanized" transgenic models have
      been used to assess potential clinical risks. These data have been useful in
      providing some assurance that severe adverse effects would not be induced in
      patients. Despite these limitations, it is important that industry sponsors
      provide information to regulatory authorities, the clinical investigator, and
      patients that provides the best feasible basis for risk assessment, safe clinical
      trial design, informed consent, and eventually, appropriate labeling. It is
      recognized that existing preclinical models often have significant limitations.
      Consequently, the sponsor's and regulatory authority's experienced judgement has
      determined whether or not the purported benefits of the novel therapeutic agent
      are balanced by the potential short- and long-term risks. In this field of
      development, preclinical models often need to reflect recent technology
      innovations; therefore, these models are not always "validated" in a conventional
      sense. Experience to date suggests that improved methods and approaches are
      needed as these agents are developed for use in lower or moderate risk patient
      populations. Consequently, there is an increased need for an industry/regulatory
      partnership in order to achieve progress in these risk assessment areas.

PMID- 10918510
TI  - Summaries of round-table discussions.

PMID- 10918511
TI  - Nonhuman primates: their role in assessing developmental effects of
      immunomodulatory agents.
AB  - There are close physiologic similarities between humans and macaques that make
      them well suited for preclinical testing of biopharmaceutics. These include
      menstrual cycles of similar length and hormonal control, comparable cellular and
      endocrine processes of implantation, and similar timetables of prenatal
      development. Three teratogenic agents have induced abnormal development of the
      macaque thymus that is a key organ in the development of the fetal immune system.
      Embryonic exposure to triamcinolone acetonide, a potent corticosteroid, during
      critical periods of thymus development caused marked hypoplasia, depletion of
      thymic lymphocytes, and reduction of epithelial elements. Aplasia and hypoplasia
      of the thymus were a distinct feature of the "retinoid syndrome" in cynomolgus
      macaques following exposure to 13-cis-retinoic acid (Accutane) in early
      pregnancy, the time of neural crest migration. Experimentally induced zinc
      deficiency in rhesus macaques from conception to 1-year of age caused severe
      alterations in immunocompetence. More recent studies have shown that the levels
      of IgG and IgA in cervicovaginal lavages of the rhesus macaque exhibit specific
      temporal patterns during the normal menstrual cycle. Taken together, theses data
      suggest that several macaque species are appropriate animal models for
      preclinical safety assessment of immunomodulatory drugs. Current teratology
      protocols in these models may require slight modifications to adequately assess
      the safety of these biologics.

PMID- 10918512
TI  - Using an analogous monoclonal antibody to evaluate the reproductive and chronic
      toxicity potential for a humanized anti-TNFalpha monoclonal antibody.

PMID- 10918513
TI  - Rapamune: a novel macrolide immunosuppressant for transplantation.

PMID- 10918515
TI  - Can host resistance assays be used to evaluate the immunotoxicity of
      pharmaceuticals?

PMID- 10918516
TI  - An overview of in vitro/ex vivo assays for preclinical evaluation of
      immunomodulation.

PMID- 10918514
TI  - Preclinical development of keliximab, a Primatized anti-CD4 monoclonal antibody,
      in human CD4 transgenic mice: characterization of the model and safety studies.
AB  - The preclinical safety assessment of biopharmaceuticals necessitates that studies
      be conducted in species in which the products are pharmacologically active.
      Monoclonal antibodies are a promising class of biopharmaceuticals for many
      disease indications; however, by design, these agents tend to have limited
      species cross-reactivity and tend to only be active in primates. Keliximab is a
      human-cynomolgus monkey chimeric (Primatized) monoclonal antibody with
      specificity for human and chimpanzee CD4. In order to conduct a comprehensive
      preclinical safety assessment of this antibody to support chronic treatment of
      rheumatoid arthritis in patients, a human CD4 transgenic mouse was used for
      chronic and reproductive toxicity studies and for genotoxic studies. In addition,
      immunotoxicity studies were conducted in these mice with Candida albicans,
      Pneumocystis carinii and B16 melanoma cells to assess the effects of keliximab on
      host resistance to infection and immunosurveillance to neoplasia. The results of
      these studies found keliximab to be well tolerated with the only effects observed
      being related to its pharmacologic activity on CD4+ T lymphocytes. The use of
      transgenic mice expressing human proteins provides a useful alternative to
      studies in chimpanzees with biopharmaceutical agents having limited species cross
      reactivity.

PMID- 10918517
TI  - Applications of immunohistochemistry in the evaluation of immunosuppressive
      agents.
AB  - Immunohistochemistry (IHC) can be a valuable endpoint to evaluate lymphocyte
      subpopulations in tissues following exposure to presumptive immunosuppressive
      agents. IHC is more sensitive than conventional histology in detecting subtle
      differences in lymphocyte numbers and distribution in tissue. In combination with
      flow cytometric analysis of peripheral lymphocyte subpopulations, IHC can
      determine if alterations detected in the peripheral blood are a result of
      trafficking or reflective of changes in tissue distribution. These techniques can
      be used to evaluate adult animals as well as to evaluate the effects of
      immunosuppressive agents on fetal tissues in reproductive toxicology studies.
      While IHC can enhance the detection of subtle changes in lymphocyte
      subpopulations in tissue, the evaluation of additional endpoints of immune
      function must be done to further assess the biological or clinical significance
      of these changes.

PMID- 10918518
TI  - Clinical trial design for immunomodulatory biologics.

PMID- 10918519
TI  - Preclinical assessments of european union marketing authorisation applications
      for immunomodulatory biopharmaceuticals.
AB  - A review of preclinical assessment reports on immunomodulatory biopharmaceuticals
      submitted to the European Agency for Evaluation of Medicinal Products from 1995
      to the middle of 1999 was conducted. Questions regarding the rationale for the
      preclinical development programmes were often put to the applicants. Effects
      mediated via changes of the immune function, including risks of reproductive
      toxicity and tumorigenicity, were of particular concern. This review indicates
      the need to further develop methods for safety testing of immunomodulatory
      biopharmaceuticals.

PMID- 10918520
TI  - Assessment of immunosuppressant drug carcinogenicity: standard and alternative
      animal models.
AB  - Drugs intended for use in preventing allograft rejection in transplant patients
      are likely to be administered chronically; thus, it is normally expected that
      sponsors would conduct nonclinical studies to determine the carcinogenic
      potential of candidate compounds. For pharmaceuticals other than biologic agents,
      this would mean that rodent carcinogenicity bioassays would be performed under
      most circumstances. Immunosuppressant drugs have presented unique challenges with
      respect to the issue of carcinogenicity bioassays. The pharmacological activity
      of therapeutic immunosuppressants is thought to make them highly likely to act as
      promoters/cocarcinogens, even in the absence of genotoxic activity. Thus, it is
      assumed that this class of drug would represent a carcinogenic hazard in the
      absence of confirmatory standard rodent bioassay data. In addition, rodents
      typically have been sensitive to the pharmacological/toxicological effects of
      immunosuppressants. It has proven to be difficult, therefore, to conduct life
      time bioassays at doses reasonably equivalent to those that would be used
      clinically. For this and other reasons, alternative models might be more
      appropriate for risk assessment with this class of drugs.

PMID- 10918521
TI  - The PCR assay in the preclinical safety evaluation of nucleic acid medicines.
AB  - The polymerase chain reaction (PCR) is a highly efficient gene amplification
      procedure which is increasingly being applied to the safety assessment of nucleic
      acid (NA) medicines such as gene therapies and DNA vaccines. Although clinical
      experience is limited, a number of potential safety issues exist with these new
      compounds including toxicity associated with the expression of encoded gene
      products, autoimmunity due to the induction of anti-DNA antibodies and
      insertional mutagenesis. PCR enables these questions to be addressed and provides
      data on mRNA expression, biodistribution and integration. In this review the use
      of PCR methodologies in the preclinical safety evaluation of NA medicines is
      discussed. Particular consideration is given to the issues surrounding the use of
      PCR in regulatory toxicology, including sensitivity requirements, cross
      contamination problems, tissue sampling procedures and good laboratory practice
      (GLP) compliance. In addition, the use of a PCR-based assay to demonstrate the
      integration of DNA vector into host DNA is described. As the use of PCR in the
      development of NA medicines will undoubtedly increase over the next few years, it
      is important that pathologists and toxicologists familiarise themselves with the
      principles and applications of this technique.

PMID- 10918523
TI  - Disruption of the reproductive system and reproductive performance by
      administration of nonylphenol to newborn rats.
AB  - A number of alkylphenolic compounds are used in a variety of commercial products
      and have been shown in in vitro studies to be weakly estrogenic, but few in vivo
      data are available addressing this issue in mammals. Human exposure to
      alkylphenols may occur not only from these environmental contaminants but also
      through contact with manufactured and metabolic breakdown products. The
      reproductive function of rats treated subcutaneously with nonylphenol (NP, 500
      mg/kg/day) or 17beta-estradiol (E2, 2 mg/kg/day) as a positive control, from
      postnatal days 1 to 5 was examined after puberty. In addition, masculine sexual
      behavior, sperm motion, plasma testosterone concentration and histopathological
      changes in the reproductive organs of the rats were examined. Furthermore, male
      rats were subjected to an open field test and wheel cage test to evaluate
      locomotor activity, and the estrous cycle was examined in female rats. All male
      and female rats exposed neonatally to NP or E2 showed macroscopic and/or
      microscopic alterations of the gonads. Females treated with NP or E2 showed an
      altered estrous cycle and abnormal reproductive function, while males treated
      with NP or E2 showed normal reproduction. In males exposed neonatally to NP or
      E2, no abnormalities were observed in locomotor activity, sperm motion or plasma
      testosterone concentration. The results of this study indicate that early
      neonatal exposure to NP causes dysfunction of postpubertal reproductive function
      in female rats, as well as disrupted development of gonads in male and female
      rats. More detailed studies are warranted to assess the possible risks to human
      and wildlife reproduction from exposure to NP and other environmental chemicals
      with estrogenic activity.

PMID- 10918522
TI  - Repeated acetaminophen dosing in rats: adaptation of hepatic antioxidant system.
AB  - Repeated dosing of acetaminophen (paracetamol) to rats is reported to decrease
      their sensitivity to its hepatotoxic effects, which are associated with oxidative
      stress and glutathione depletion. We determined if repeated acetaminophen dosing
      produced adaptive response of key antioxidant system enzymes. Male rats (Sprague
      Dawley, 10 weeks) were given 800, 1200, or 1600 mg/kg/day acetaminophen by oral
      gavage for 4 days. Liver was assayed for oxidative stress and antioxidant
      markers: malondialdehyde (MDA), thiobarbituric acid reactive substance (TBARS),
      total antioxidant status (TAS), glutathione (GSH), glutathione reductase (GR),
      glutathione peroxidase (GPx), glucose-6-phosphate dehydrogenase (G6PD), catalase
      (CAT), and superoxide dismutase (SOD), and alanine transaminase (ALT) as a marker
      of hepatocellular injury. Acetaminophen at 1200/1600 mg/kg decreased GSH 26/47%,
      GPx 21/26%, CAT 35/28%, SOD 21/12%; and TAS 28/18% (correlated with CAT, r=0.91;
      SOD, r=0.66; GPx, r=0.45). Despite antioxidant deficiencies, and no TBARS change,
      MDA decreased 26%/33%/37% at 800/1200/1600 mg/kg, which correlated with increased
      GR (61%/62%/76%, r=0.77) and G6PD (130%/110%/190%, r=0.78). Both MDA (r=0.68) and
      G6PD (r=0.71) correlated with hepatic ALT, which decreased 27%/43%/48%,
      respectively. Resistance to acetaminophen hepatotoxicity produced by repeated
      exposure is partially attributable to upregulation of hepatic G6PD and GR
      activity as an adaptive and protective response to oxidative stress and
      glutathione depletion.

PMID- 10918524
TI  - Cholinergic and noncholinergic brain biomarkers of insecticide exposure and
      effects.
AB  - The objective of this investigation was to determine the distribution of
      cholinergic and noncholinergic biomarkers in discrete brain regions (cortex,
      stem, striatum, hippocampus, and cerebellum) of rats treated with dimethyl
      sulfoxide (DMSO, controls), and insecticides such as carbofuran (CARB, 1.5 mg/kg,
      sc), or methyl parathion (MPTH, 5 mg/kg, ip). Both insecticides produced
      characteristic signs of anticholinesterase nature within 5-7 min after injection.
      In controls, analyses of the brain regions revealed a wide variability in the
      values of cholinergic (acetylcholinesterase, AChE) and noncholinergic (creatine
      kinase, CK; and lactic dehydrogenase, LDH, and their isoenzymes) biomarkers. The
      highest activities of AChE and LDH were found in the striatum (1661+/-23
      micromol/g/h and 57,720+/-478 IU/l, respectively) and lowest in the cerebellum
      (118+/-6 micromol/g/h) and 39,480+/-918 IU/l, respectively). However, the
      activity of CK was found highest in the cerebellum (742,560+/-798 IU/l) and
      lowest in the hippocampus (353,400+/-11,696 IU/l). Each brain region showed a
      characteristic profile of CK and LDH isoenzymes. Among the CK isoenzymes,
      activity of CK-BB was highest (77.5-89.3%), followed by CK-MM (6.7-15.6%), and
      least CK-MB (0-6.9%). The cerebellum had no CK-MB activity. In all brain regions,
      CK-MM isoenzyme had only the CK-MM3 subform. Among the LDH isoenzymes, activity
      of LDH-4 was highest in all brain regions (23-40%), except the cerebellum in
      which LDH-1 was highest (29%). Compared to the brain, control serum contained
      very little CK and LDH activity, but serum had three distinct CK and five
      distinct LDH isoenzymes. Unlike brain regions, serum had three CK-MM subforms.
      Each insecticide induced characteristic alterations in brain biomarkers. AChE
      activity was maximally inactivated in cortex (90. 6%) with CARB, and in
      cerebellum (95.3%) with MPTH. With either insecticide, the least inhibition of
      AChE occurred in the striatum. Unlike AChE, carboxylesterase (CarbE) did not show
      brain regional variability in controls, and its activity was uniformly inhibited
      in all brain regions by CARB and comparatively greater by MPTH. CARB- or MPTH
      induced characteristic alterations in CK, LDH, and their isoenzymes in the brain,
      which were also reflected in serum, as a result of their leakage from the brain
      by increased permeability due to depletion of ATP (38-57% and 33-47%,
      respectively) and phosphocreatine (PCr, 23-42% and 56-65%, respectively).

PMID- 10918526
TI  - Changes in the distribution of body mass index of adults and children in the US
      population.
AB  - BACKGROUND: National survey data show increases in mean body mass index (BMI) and
      in the prevalence of overweight and obesity for adults and children in the United
      States, indicating a change in the distribution of BMI. OBJECTIVE: To apply
      graphical methods to describe changes in the distribution of BMI. DESIGN: BMI
      values from the third National Health and Nutrition Examination Survey (NHANES
      III: 1988-94) were compared with data from earlier cross-sectional nationally
      representative surveys for adults 20-74 y of age and for children and adolescents
      6-17 y of age. Tukey mean-difference plots were used to investigate the changes
      in the distributions of BMI within sex-age groups. RESULTS: Mean-difference plots
      allow qualitative visual comparisons of the distributions of BMI between surveys.
      For all sex-age groups, there was increasing skewness with a greater shift in the
      upper part of the distribution so that, within each group, the heaviest subgroup
      was heavier in NHANES III than in prior surveys. For the youngest children, the
      lower part of the distribution showed virtually no change. With increasing age
      the whole distribution tended to shift upward slightly, suggesting an increase in
      BMI across the entire population. CONCLUSIONS: These changes in the distribution
      of BMI suggest the combination of both profound environmental determinants and a
      population with a high degree of susceptibility. The reasons for the increasing
      prevalence of obesity should be sought in part by seeking to understand the
      factors causing increases in the population as a whole.

PMID- 10918525
TI  - Manipulation of the phenotype of immortalised rat hepatocytes by different
      culture configurations and by dimethyl sulphoxide.
AB  - The liver-specific phenotype of immortalised rat hepatocytes is not irretrievably
      lost as they age in culture but can be manipulated by modifying the culture
      environment. Testosterone metabolism was used to investigate the profile of
      cytochrome P450 isoenzymes present in two immortalised cell lines, P9 and LQC,
      and in primary cultures of rat hepatocytes, cultured on collagen films, gels and
      double gel cultures (sandwich configuration). The extent of testosterone
      metabolism, and the range of metabolites produced, was increased in immortalised
      cells by the presence of collagen as a substratum film or gel but survival was
      poorer and the range of metabolites was reduced in sandwich culture. In contrast,
      testosterone metabolism was retained in primary hepatocytes in sandwich cultures
      at a higher level than in collagen film or gel cultures. Expression of alpha
      class glutathione-S-transferases (GSTs) increased and that of GSTP1 decreased
      (changes which indicate a recovery of normal liver GST phenotype) when the medium
      of immortalised cell cultures was supplemented with dimethyl sulphoxide (DMSO).
      DMSO also improved ethoxyresorufin O-deethylation (EROD) and testosterone
      metabolism in immortalised cells. It also markedly inhibited proliferation, DNA,
      RNA and protein synthesis. Maximal testosterone metabolism was observed in
      immortalised cells cultured on collagen gels in the presence of 1% (v/v) DMSO.
      Development of a protocol for treating immortalised liver cells cultured on
      collagen gels with DMSO to switch between proliferation and differentiation may
      provide a convenient system expressing the xenobiotic metabolising enzymes
      required for in vitro toxicity testing.

PMID- 10918527
TI  - Chronically increased intra-abdominal pressure produces systemic hypertension in
      dogs.
AB  - OBJECTIVE: Determine if increased intra-abdominal pressure (IAP) alone can cause
      systemic hypertension in a chronic canine model. DESIGN: Evaluate effects of
      increase in IAP with progressive inflation and deflation of an intra-abdominal
      balloon on systemic blood pressure in experimental and control animals. SUBJECTS:
      Male dogs weighing 15-25 kg underwent placement of an intra-abdominal balloon
      which was progressively inflated on a weekly basis in the experimental animals
      (5) over 4 weeks to 25 mmHg above baseline and kept there for an additional 2
      weeks before gradual deflation over 2 weeks. Control animals (5) had the balloon
      placed but not inflated. Pain was controlled with osmotic analgesic pumps.
      MEASUREMENTS: The animals were anesthetized, blood pressure (BP) measured and
      blood drawn for plasma renin activity (PRA), aldosterone, atrial naturetic
      peptide (ANP), catecholamines, and serum sodium (Na). A right heart catheter was
      inserted for measuring cardiac output (CO) and pulmonary artery occlusion
      pressure (PAOP) at baseline, week 5 (maximal IAP) and week 7 (after balloon
      deflation). The animals were weighed and urinary bladder pressures recorded
      weekly before and after abdominal balloon inflation. RESULTS: Systolic (122+/-3
      to 155+/-5 mmHg, P<0.05) and diastolic (82+/-4 mmHg to 107+/-7 mmHg, P<0.05) BP
      rose at 5 weeks at 25 mmHg IAP>baseline and returned to control with balloon
      deflation. Both systolic and diastolic BP rose (P<0.05) above control animals BP
      at 15 mmHg IAP at 2 weeks and remained elevated until abdominal decompression, at
      week 7. There were no significant changes in net animal weight, PRA, aldosterone,
      ANF, catecholamines, Na, CO or PAOP. CONCLUSION: Increased IAP from progressively
      inflating an intra-abdominal balloon in dogs was associated with significant
      increases in systolic and diastolic BP that resolved with balloon deflation.
      Increased IAP may be a cause for systemic hypertension in central obesity and pre
      eclampsia.

PMID- 10918528
TI  - Lower insulin sensitivity as an independent risk factor for carotid wall
      thickening in normotensive, non-diabetic, non-smoking normal weight and obese
      premenopausal women.
AB  - OBJECTIVE: Increased thickness of the intima-media complex of the common carotid
      artery (IMT-CCA) is an early marker of atherosclerosis. The aim of the present
      study was to investigate the relationship between insulin resistance and IMT-CCA
      in premenopausal women. SUBJECTS: 86 young women, aged 18-31 y, were recruited
      for the study: 28 were normal weight (BMI<25 kg/m2), 23 were overweight (BMI 25
      30 kg/m2) and 35 were obese (BMI>30 kg/m2). MEASUREMENTS: The IMT-CCA was
      measured by high resolution 'B-mode' ultrasonography; insulin sensitivity was
      determined by insulin tolerance test (ITT) and quantitated by calculation of
      KITT. Fasting plasma glucose and lipids (triglycerides, total and HDL
      cholesterol) were also measured by enzymatic methods. Central fat accumulation
      was evaluated by measuring waist circumference (WC). RESULTS: IMT-CCA showed an
      inverse association with KITT (P<0.05). When the IMT-CCA was considered as the
      dependent variable in a forward stepwise multiple regression analysis, it
      maintained an independent association with KITT (P<0.05), after adjusting data
      for age, BMI, WC, mean blood pressure levels and plasma glucose and lipids.
      CONCLUSION: These results suggest that IMT-CCA is significantly associated with
      insulin resistance, independent of other well-known CVD risk factors. Since the
      IMT-CCA is an earlier asymptomatic sign of atherosclerosis, this study indicates
      that insulin resistance per se may accelerate atherogenesis.

PMID- 10918530
TI  - Total body fat does not influence maximal aerobic capacity.
AB  - OBJECTIVE: The objective of this study was to examine the influence of body
      weight and body composition on aspects of aerobic fitness. Our hypothesis was
      that increased body weight, specifically increased fat mass (FM), would not limit
      VO2max relative to fat-free mass (FFM), but would reduce maximal and sub-maximal
      VO2max relative to body weight. DESIGN: We used data from two ongoing studies. In
      Study 1 a cross-sectional analysis of 129 children across a wide spectrum of body
      composition was performed. In Study 2 we examined data from 31 overweight women
      before and after weight loss. METHODS: VO2max was measured using a treadmill
      test. Sub-maximal aerobic capacity was evaluated with respiratory exchange ratio
      (RER), heart-rate (HR), and oxygen uptake relative to VO2max at a given workload
      (%VO2max). Body composition was assessed using dual energy X-ray absorptiometry
      (DXA) (Study 1) and a four-compartment model (Study 2). RESULTS: In Study 1, FFM
      was the strongest determinant of VO2max (r=0.87; P<0.0001). After adjusting for
      FFM, there was no significant influence of FM on VO2max. After separating
      children into lean and obese sub-groups, absolute VO2max was significantly higher
      in the obese (1.24+/-0.27 vs 1.56+/-0.40) and VO2max relative to body weight was
      significantly lower (44.2+/-3.2 vs 32.0+/-4.1 ml/(kg-min)), whereas there was no
      significant difference when expressed relative to FFM (57.9+/-5.8 vs 59.2+/-4.9
      ml/(kgFFM-min)). Sub-maximal aerobic capacity was significantly lower in the
      obese children, as indicated by a higher HR and %VO2max; time to exhaustion was
      significantly lower in the obese children (15.3+/-2.9 vs 11.1+/-2.1 min). In
      Study 2, FFM was also the strongest determinant of VO2max before and after weight
      loss. The relationship between VO2max and FFM was identical before and after
      weight loss so that VO2max relative to FFM was identical before and after weight
      loss (43.8+/-4.9 vs 45.5+/-6.4 ml/(kgFFM-min)). However, sub-maximal aerobic
      capacity was lower in the obese state, as indicated by a significantly higher RER
      (0.85+/-0.06 vs 0.79+/-0.05), HR (124+/-14 vs 102+/-11 bpm), and %VO2max (44% vs
      36%). CONCLUSION: The major influence of body weight on VO2max is explained by
      FFM; FM does not have any effect on VO2max. Fatness and excess body weight do not
      necessarily imply a reduced ability to maximally consume oxygen, but excess
      fatness does have a detrimental effect on submaximal aerobic capacity. Thus,
      fatness and VO2max should be considered independent entities.

PMID- 10918529
TI  - Effects of the estrogen antagonist EM-652.HCl on energy balance and lipid
      metabolism in ovariectomized rats.
AB  - OBJECTIVE: The estrogen antagonist EM-652.HCl behaves as a highly potent and pure
      antiestrogen in human breast and uterine cancer cells. Because of its pure
      antiestrogenic activity in these cells, and because its prodrug, EM-800, reduces
      bone loss and decreases serum cholesterol and triglycerides in the rat, EM
      652.HCl can be classified as a pure selective estrogen receptor modulator (SERM).
      This study was conducted to assess the ability of EM-652.HCl to prevent obesity
      and abnormalities of lipid metabolism induced by ovariectomy in a rat model.
      DESIGN: Female rats were left intact or ovariectomized (OVX), and OVX rats were
      treated with placebo, estradiol (E2), or EM-652.HCl for 20 days. At the end of
      the treatment period, parameters of energy balance and determinants of lipid
      metabolism were assessed. RESULTS: As expected, OVX increased energy intake,
      which in turn was accompanied by an increased energy, fat and protein gain and
      higher food efficiency. OVX also increased the triglyceride content of the liver
      and produced hypercholesterolemia and hyperinsulinemia. The weight of
      representative white adipose depots was higher in OVX than in intact rats.
      Lipoprotein lipase activity was higher in white adipose tissues of OVX rats than
      in those of intact animals, whereas its activity was lower in oxidative tissues
      (brown adipose and soleus muscle). Replacement therapy with a physiological dose
      of E2 prevented most of the abnormalities in energy and lipid metabolism brought
      about by OVX, although its orexigenic effect was only partially corrected. In
      contrast, treatment of OVX rats with EM-652. HCl completely abolished OVX-induced
      obesity and its related abnormalities in lipid metabolism and glucose/insulin
      homeostasis. CONCLUSION: These findings demonstrate that EM-652.HCl can be
      considered as an effective agent to prevent OVX-induced obesity. The present
      study also shows that EM-652.HCl reduces cardiovascular risk factors associated
      with obesity such as hyperlipidemia and insulin resistance.

PMID- 10918531
TI  - Relation of generalized and central obesity to cardiovascular risk factors and
      prevalent coronary heart disease in a sample of American Indians: the Strong
      Heart Study.
AB  - OBJECTIVE: To examine the hypothesis linking measures of obesity including body
      mass index (BMI), waist circumference (waist) and percentage body fat to coronary
      heart disease (CHD) prevalence and its risk factors in American Indians. DESIGN:
      The Strong Heart Study assesses the prevalence of CHD and its risk factors in
      American Indians in Arizona, Oklahoma and South/North Dakota. Participants
      underwent a physical examination and an electrocardiogram; anthropometric and
      blood pressure measurements were taken, as were measurements of glucose,
      lipoproteins, fibrinogen, insulin, hemoglobin A1c and urinary albumin.
      PARTICIPANTS: Data were available for 4549 men and women between 45 and 74 y of
      age. MEASUREMENTS: Obesity, measured using body mass index, waist circumference
      and percentage body fat, was correlated with prevalent CHD and its risk factors.
      RESULTS: More than 75% of participants were overweight (BMI>25 kg/m2). Measures
      of obesity were greater in women than in men, in younger than in older
      participants, and in participants with diabetes than in nondiabetic participants.
      CHD risk factors were associated with measures of obesity but, except for insulin
      concentration, changes in metabolic variables with increasing obesity were small.
      Associations were not stronger with waist than with BMI. The prevalence of CHD in
      those whose BMI and/or waist measurements lay in the lowest and highest
      quintiles, by gender and diabetic status, was similar. CONCLUSIONS: Although CHD
      risk factors are associated with obesity in American Indians, distribution of
      obesity (ie waist) is no more closely related to risk factors than is generalized
      obesity (ie BMI), and changes in CHD risk factors with obesity were small. Thus,
      the relations among obesity, body fat distribution and CHD risk may differ in
      this population.

PMID- 10918533
TI  - Overweight and obesity in Brazilian adolescents.
AB  - OBJECTIVE: This study aimed to describe the prevalence of overweight and obesity
      (OW+O) among Brazilian adolescents and to identify risks for subpopulations
      defined according to the five country macro-regions and situation (urban-rural)
      of the domiciles, income, years of school attendance, age and sex. DESIGN: A
      nationwide home-based survey representative of the Brazilian civilian
      noninstitutionalized population, performed in 1989. METHODS: The sampling plans
      followed a stratified, multistage, probability cluster design in The National
      Research of Health and Nutrition sample, which collected anthropometric data of
      14,455 domiciles. In all, 13,715 adolescents ranging from 10 to 19 y of age were
      studied. The OW+O was defined from a body mass index (BMI) equal or superior to
      the 85th percentile of the reference population of the NCHS. The prevalences in
      the different studied groups were compared using the adjusted odds ratio in
      logistic regression models. RESULTS: The prevalence of OW+O was of 7.7%, reaching
      10.6% within the female group and 4.8% within the male group. A direct relation
      could be established between the socioeconomic level and OW+O. Adolescents of the
      most industrialized region of the country presented a risk of OW+O 1.86 (95% CI
      1.51-2.30) times higher than that found in the least developed region. Male
      youngsters who lived in urban areas were more liable (OR=1.71, 95% CI 1.30-2.25)
      to overweight than their counterparts of rural areas. The occurrence of menarche
      increased two and a half times (OR=2.58, 95% CI 2.11-3.15) the risk of OW+O
      within the female group of adolescents. CONCLUSIONS: The results demonstrate a
      low prevalence of OW+O among Brazilian adolescents when compared with adolescents
      of more industrialized regions. The OW+O is twice as high within the female
      group, which represents a much greater difference than the one encountered in
      industrialized countries, probably owing to the muscular work carried out
      preponderantly by male adolescents of lower socioeconomic levels. Higher
      prevalences in subpopulations of higher socioeconomic level and of more
      industrialized regions show the great need for differentiated actions to control
      overweight and obesity in the country.

PMID- 10918532
TI  - Genomic structure and mutations in adipose-specific gene, adiponectin.
AB  - BACKGROUND: Adiponectin is a collagen-like plasma protein specifically
      synthesized in adipose tissue. Plasma adiponectin concentrations are decreased in
      obesity whereas it is adipose-specific. OBJECTIVE: To clarify the significance of
      the genetic variations in adiponectin gene on its plasma concentrations and
      obesity. SUBJECTS: Two hundred and nineteen unrelated adult Japanese subjects
      (123 men and 96 women, age: 20-83 y, BMI: 16-43 kg/m2) including 77 obese
      subjects (BMI>26.4 kg/m2). MEASUREMENT: Human adiponectin gene was isolated from
      PAC DNA pools. Mutations in the adiponectin gene were screened by direct
      sequencing or restriction-fragment polymorphism. The levels of plasma adiponectin
      were determined by the enzyme-linked immunosorbent assay (ELISA). RESULTS:
      Adiponectin gene spanned 17 kb on chromosome 3q27, consisting of three exons and
      two introns. Within 2.1 kb of the 5'-flanking region, there were two octamer
      elements present in the promoter of adipsin. Two nucleotide changes were
      identified. One was a polymorphism (G/T) occurring in exon 2, and the other was a
      missense mutation (R112C) in exon 3. The mean plasma adiponectin levels of the
      subjects carrying G allele were low (G/G: 4.5 microg/ml; G/T: 5.9 microg/ml; and
      T/T: 6.3 microg/ml), but were not statistically significant. The allelic
      frequency between the obese and the non-obese showed no significant difference.
      The subject carrying R112C mutation showed markedly low concentration of plasma
      adiponectin. CONCLUSION: Two nucleotide changes have been identified in the
      adiponectin gene. G/T polymorphism in exon 2 was associated with neither plasma
      adiponectin concentrations nor the presence of obesity. A subject carrying
      missense mutation (R112C) showed markedly low plasma adiponectin concentration.

PMID- 10918534
TI  - Gender differences in the regulation of P450 aromatase expression and activity in
      human adipose tissue.
AB  - OBJECTIVE: To investigate the hormonal regulation of P450 aromatase activity
      (responsible for the conversion of C19 androgens to C18 oestrogens) in human
      adipose tissue from men and pre- and post-menopausal women. SUBJECTS:
      Subcutaneous abdominal adipose tissue was obtained from 19 subjects: six pre
      menopausal females (mean age 41.8+/-(s.e.m.) 2.5; mean weight 76.01+/-5.6 kg),
      eight post-menopausal females (mean age 59.9+/-2.0; mean weight 63.5+/-2.6 kg),
      and five males (mean age 35.8+/-8.8; mean weight 78.5+/-7.8 kg) undergoing
      elective or cosmetic surgery. MEASUREMENTS: Cell viability and cell size were
      determined using staining techniques. RT-PCR was used to confirm the presence of
      aromatase. The regulation of aromatase activity was characterized using
      androstenedione as a substrate in a tritiated water release assay. Aromatase
      activity was analysed in abdominal subcutaneous stromal cells (ASC) and mature
      adipocytes (AD) cultured in serum-free medium with cortisol (10-6-10-7 M),
      insulin (500 nM) or a combination of both. RESULTS: In ASC aromatase activity
      increased in females from 14.5+/-1.7 to 29. 3+/-2.6 pmol/mg/h (n=14, P<0.05) and
      to 25.2+/-2.1 pmol/mg/h with cortisol (10-7 M) and insulin, respectively
      (P<0.05). In males ASC basal aromatase activity (20.5+/-4.2 pmol/mg/h; n=5) was
      inhibited by cortisol (10-7 M) alone (12.3+/-1.8 pmol/mg/h) and in combination
      with insulin (6.6+/-1.2 pmol/mg/h; men vs women, P<0.005). Aromatase activity in
      mature adipocytes was stimulated by cortisol plus insulin (P<0.05) with no gender
      specific differences. Treatment of ASC from both pre- and post-menopausal females
      with cortisol alone (10-6 M; 10-7 M) or in combination with insulin demonstrated
      significantly different aromatase regulation compared with male aromatase stromal
      cell regulation (P<0.05); however there were no differences in aromatase
      regulation between pre- and post-menopausal females either in stromal cells or
      adipocytes. CONCLUSION: This study shows intrinsic gender differences in the
      regulation of aromatase, suggesting that differential enzyme regulation may
      affect sex steroid metabolism to alter the pattern of fat distribution between
      the sexes.

PMID- 10918535
TI  - Underreporting of energy intake in four populations of African origin.
AB  - OBJECTIVE: To investigate the frequency of dietary underreporting in four African
      populations in different geographic and cultural settings. SUBJECTS: Seven
      hundred and forty three men and women from rural Cameroon, 1042 men and women
      from urban Cameroon, 857 men and women from Jamaica and 243 male and female
      African Caribbeans from the UK. Subjects who reported dieting or weight control
      were excluded. MEASUREMENTS: Habitual dietary intake was estimated with a
      quantitative food frequency questionnaire, developed specifically for each
      country. Underreporting was defined using three cut-off levels for energy
      intake/estimated basic metabolic rate (EI/BMRest), based on age, sex and weight,
      in each site. RESULTS: The EI/BMRest was highest in rural Cameroonian men at 3.07
      (95% confidence interval: 2.97, 3.17) and women at 2.84 (2.74, 2.94),
      intermediate in urban Cameroon and Jamaica and lowest in the UK men and women at
      1.44 (1.26, 1.62) and 1.41 (1.21, 1.61). This trend existed even after adjustment
      for age, BMI and education (P for trend<0.0001). The trend in the frequency of
      underreporting using the lowest cut-off level for EI/BMRest of 1.15 was 6% and 6%
      in rural Cameroon for women and men, respectively, 4% and 5% in urban Cameroon,
      24% and 19% in Jamaica and 28% and 39% in the UK. With higher cut off levels this
      trend was similar. CONCLUSION: The results suggest that the frequency of dietary
      underreporting differs between societies and that Westernization may be one of
      the factors underlying this phenomenon.

PMID- 10918536
TI  - Open-loop feedback to increase physical activity in obese children.
AB  - OBJECTIVE: The present study investigated whether making access to sedentary
      activities contingent on physical activity would increase physical activity.
      DESIGN: Experimental. PARTICIPANTS: Thirty-four obese children aged 8-12 y were
      randomized to one of three groups in which children had to accumulate 750 or 1500
      pedometer counts to earn 10 min of access to video games or movies, or to a
      control group in which access to sedentary behaviors was provided
      noncontingently. MEASUREMENTS: Physical activity in the 20 min experimental
      session was measured by electronic pedometer and triaxial accelerometer (ie
      TriTrac(R)). Activity liking was measured by visual analog scales. Anthropometric
      and demographic characteristics were also assessed. RESULTS: Children in the 750
      and 1500 count contingency groups engaged in significantly more physical activity
      and spent more time in moderate intensity activity or higher compared with
      controls. Children in the Contingent 1500 group engaged in more activity and
      spent more time in moderate or greater intensity activity compared to children in
      the Contingent 750 group. CONCLUSION: Findings suggest that contingent access to
      sedentary activities can reinforce physical activity in obese children, and
      changes in physical activity level depend in part on the targeted physical
      activity goal.

PMID- 10918537
TI  - Effective long-term treatment of obesity: a continuing care model.
AB  - BACKGROUND: Despite the well-documented success of behavioral techniques in
      producing temporary weight loss, treatment is typically followed by weight
      regain. The maintenance of treatment effects may therefore be the greatest
      challenge in the long-term management of obesity, and continuous care may be
      necessary to achieve it. OBJECTIVE: To describe the design and evaluate the
      effectiveness of the Trevose Behavior Modification Program, a potentially widely
      replicable self-help weight loss program offering continuous care. DESIGN: A
      description of the course of all subjects (n=171) who entered the Trevose program
      during 1992 and 1993. SUBJECTS: One hundred and forty-six women aged 44.1+/-11.7
      y with a body mass index (BMI, kg/m2) of 33.2+/-4.4, and 25 men aged 49. 0+/-19.6
      with a BMI of 35.1+/-5.2 enrolled in the Trevose program during 1992-1993.
      RESULTS: Mean duration of treatment was 27.1 months, with 47.4% of members still
      in treatment at 2 y and 21.6% at 5 y. Mean intent-to-treat weight loss was 13.7+/
      0.5% of initial weight, or 12.8+/-0.5 kg. As long as they remained in treatment,
      almost all participants lost at least 5% of their initial weight and at least 83%
      lost more than 10%. Members completing 2 y of treatment lost an average of 19.3%
      of their initial body weight (17.9 kg); at 5 y the loss was still 17.3% (15.7
      kg). After leaving the program, subjects regained weight but remained 4.7% (4.5
      kg) below their pretreatment weight. CONCLUSION: A low-cost program offering
      treatment of indefinite duration produced large long-term weight losses and may
      be suitable for widespread replication.

PMID- 10918538
TI  - Effect of obesity and major weight reduction on gastric emptying.
AB  - BACKGROUND: An enhanced gastric emptying rate might reduce the satiating effect
      of food and thereby promote obesity. Gastric emptying rate has previously been
      compared between obese and lean subjects with conflicting outcome. OBJECTIVE:
      Comparison of gastric emptying rate in lean and obese subjects before and after a
      major weight reduction. DESIGN: The study was designed as a case-control study
      comparing obese and lean subjects and a subsequent comparison of obese subjects
      before and after a dietary induced major weight reduction. METHOD: Gastric
      emptying rate following a solid test meal was estimated scintigraphically for 3 h
      using the left anterior oblique projection. SUBJECTS: Nineteen non-diabetic obese
      (mean BMI=38.7 kg/m2) and 12 lean (mean BMI=23.1 kg/m2) males matched for age and
      height. All obese subjects were re-examined after a mean weight loss of 18.8 kg
      (95% CI, 14.4-23.2) achieved by 16 weeks of dietary intervention followed by 8
      weeks of weight stability. RESULTS: When comparing obese and lean subjects no
      differences were seen in overall 3 h emptying rate (30.3% per hour vs 30.5% per
      hour). However, a trend towards a higher percentage gastric emptying during the
      initial 30 min was seen in the obese when compared to lean subjects (24.0% vs
      17.8% of the test meal; P=0.08). Weight loss was associated with a reduction in
      percentage gastric emptying during the initial 30 min (from 24.0% to 18.3% of the
      test-meal; P<0. 02), whereas the overall 3 h emptying rate was unaffected (30.3%
      vs 30.9% per hour). Neither initial or overall emptying rate differed between
      reduced-obese and lean subjects. CONCLUSION: Overall 3 h gastric emptying rate
      was similar in obese and normal weight males, and unaffected by a major weight
      loss. However, percentage gastric emptying during the initial 30 min for a solid
      meal appeared to be increased in obese males and was normalized after a major
      weight reduction.

PMID- 10918539
TI  - Appetite after weight loss by energy restriction and a low-fat diet-exercise
      follow-up.
AB  - OBJECTIVE: The aim of the present study was to determine the impact of weight
      loss on appetite as measured by visual analog scale (VAS). METHODS: Seventeen
      subjects (10 men and seven women) took part in a 15 week weight loss program
      which consisted of drug therapy (fenfluramine 60 mg/day) or placebo coupled to an
      energy restriction (-2930 kJ/day; phase 1) followed by an 18 week low-fat diet
      exercise follow-up (phase 2). Subjects were given a standardized breakfast before
      and after phase 1 as well as after phase 2. Individuals were asked to fill out
      VAS before and at 0, 10, 20, 30, 40, 50 and 60 min after this test meal. Blood
      samples were drawn before the meal and at 0, 30 and 60 min postprandially and
      analyzed for glucose and insulin. Fasting plasma cortisol and leptin were also
      determined. RESULTS: An increase in the fasting desire to eat, hunger and
      prospective food consumption (PFC) was observed after phase 1 and to an even
      greater extent after phase 2 in both men and women. In the fasting state,
      positive correlations were observed between changes in the desire to eat (r=0.76;
      P<0.05) as well as changes of PFC (r=0. 82; P<0.05) and changes in cortisol at
      the end of phase 1 for women. In response to phase 1, statistically significant
      correlations were found between changes of hunger (r=0.64; P<0.05) and desire to
      eat (r=0.67; P<0.05) as measured by AUC in response to the meal and changes of
      fasting plasma cortisol in men. The most consistent predictor of changes of
      baseline desire to eat (r=0.68 P<0.05), fullness (r=-0.78, P<0.05) and PFC
      (r=0.91, P<0.01) during phase 2 was the change in fasting cortisol in men.
      Changes of fullness were also associated with changes of fasting leptin in men
      (r=0.68; P<0. 05) during phase 2. CONCLUSION: These results suggest that weight
      loss is accompanied by an increase of baseline appetite in both men and women and
      that the most consistent predictor of these changes in appetite seems to be
      changes in fasting plasma cortisol.

PMID- 10918540
TI  - Lymphocyte glucocorticoid receptor mRNA correlates negatively to serum leptin in
      normal weight subjects.
AB  - OBJECTIVE: The aim of the present study was to test the hypothesis that
      glucocorticoid receptor mRNA concentrations decreased with increasing fatness in
      normal subjects. MEASUREMENTS: Serum leptin concentrations, fat distribution
      parameters, lymphocyte glucocorticoid (GCR) mRNA, beta2-adrenoceptor mRNA and c
      fos mRNA concentrations measured by RT-PCR-HPLC. SUBJECTS: Fifteen healthy non
      obese young subjects with a mean body mass index (BMI) of 23. 5+/-0.3 (+/-s.e.m.)
      kg/m2. RESULTS: Lymphocyte GCR and beta2-adrenoceptor mRNA concentrations
      averaged 4.2+/-0.2 (+/-s.e.m. ) amol/microg total RNA and 1.4+/-0.1 amol/microg
      total RNA, respectively. There was a significant negative correlation between
      serum leptin and lymphocyte GCR mRNA (P<0.01). Serum leptin correlated positively
      with the waist-hip ratio (P<0.03), whereas lymphocyte GCR mRNA correlated
      negatively to the waist-hip ratio (P<0.04). Serum cortisol correlated with the
      weight of the subjects but not the waist-hip ratio or GCR mRNA. CONCLUSIONS: It
      is suggested that the decrease in lymphocyte GCR mRNA concentration with
      increasing serum leptin concentrations is a counterregulatory response to an
      increased body fat content. Further studies are warranted, especially to
      elucidate the relationship between GCR mRNA in lymphocytes and in fat cells and
      to clarify the mechanism of the decrease in GCR mRNA.

PMID- 10918541
TI  - 5-HT2A receptor gene polymorphism is associated with food and alcohol intake in
      obese people.
AB  - OBJECTIVE: To test the association between a polymorphism of the 5-HT2A receptor
      gene, -1438G/A, and energy and nutrients intake, including alcohol. SUBJECTS: Two
      hundred and seventy six unrelated overweight subjects (180 women, 96 men) were
      recruited from the Nutrition Department of Bichat Hospital in Paris on the basis
      of 120% of ideal body weight (body mass index, BMI=33.3+/-4.8 kg/m2). A second
      overweight sample (31 women, 49 men) was drawn from the Stanislas Family Study,
      composed of volunteers for a free health examination in Nancy (BMI=29.6+/-3.1
      kg/m2). MEASUREMENTS: Energy and nutrients intake were assessed using the diet
      history method in Paris and the 3-day record method in Nancy. We analyzed the
      polymorphism by PCR followed by MspI digestion. Statistical differences between
      genotypes were assessed by using the non-parametric Kruskal-Wallis test. RESULTS:
      In the whole overweight population, the A allele was associated with lower energy
      intake 10. 3+/-2.8, 9.9+/-2.8, 9.3+/-2.9 MJ/day for GG, GA and AA genotypes
      respectively (P<0.05). This association was significant in the patient sample
      from Paris and in the overweight male volunteers from Nancy. Allele A-related
      lowering in energy intake was due to a trend to lower intakes in all the main
      nutrients. The A allele was also associated with a lower alcohol consumption:
      18.4+/-19.7, 15.3+/-21. 2 and 12.3+/-17.5 g/day for GG, GA and AA genotypes,
      respectively (P<0.05). CONCLUSIONS: These data indicate that a gene polymorphism
      may influence food and alcohol intake in overweight humans. This could be
      explained by the role of the serotonergic system as a determinant of food intake.

PMID- 10918542
TI  - Trends in body mass index and overweight prevalence among children and
      adolescents in the region of Aragon (Spain) from 1985 to 1995.
AB  - OBJECTIVE: To analyse trends in body mass index (BMI) and overweight prevalence
      for children and adolescents in the region of Aragon (Spain), from 1985 to 1995.
      DESIGN: Nine cross-sectional examinations of schoolchildren conducted yearly from
      1985 to 1995. SUBJECTS: A total of 90,997 children (45,970 males and 45,027
      females) in the first school year (6-7 y of age); 106,284 scholars (52,772 males
      and 53,512 females) in the last school year (13-14 y of age). MEASUREMENTS:
      Heights and weights were measured and BMI (kg/m2) was calculated. RESULTS: We
      observed a trend to higher BMI values across the surveys, by sex and age. The
      secular trends in BMI showed the largest increases at the upper ends of the
      distribution, especially in males. In children in the first school year,
      prevalences of overweight were higher in females than in males (P<0. 001);
      however, in adolescents in the last school year, prevalences were higher in males
      than in females (P<0.001). We observed a significant trend in overweight
      prevalence from 1985 to 1995 in children from the first school year (P=0.0183, in
      males and P=0.0168, in females). In children in the last school year there was
      only a significant trend in males (P<0.0001). CONCLUSION: Significant changes in
      BMI occurred in the population studied during the period 1985-1995, but these
      changes differ by age and sex. The increasing skewness of BMI in the upper
      percentiles of the population, especially in boys, suggests that, not only is the
      pediatric population getting fatter, but the fatter members are becoming more
      obese. Our results also show a striking increase in the prevalence of overweight
      children in the region of Aragon (Spain) during the 1985-1995 decade.

PMID- 10918544
TI  - Blood pressure measurement: worsening chaos.

PMID- 10918543
TI  - De novo lipogenesis in adipose tissue of lean and obese women: application of
      deuterated water and isotope ratio mass spectrometry.
AB  - OBJECTIVE: To evaluate the feasibility of using deuterated water and isotope
      ratio mass spectrometry to measure de novo fatty acid synthesis in adipose
      tissue, and to compare this parameter in obese and lean women. SUBJECTS: Six lean
      and six obese premenopausal Caucasian women in the main study and three obese
      Pima Indians in a pilot study. MEASUREMENTS: Deuterated water was administered
      orally twice daily for 14 days to create stable deuterium enrichment in body
      water, during which series of blood samples were collected to measure body water
      deuterium enrichment and deuterium incorporation into plasma total
      Triacylglycerol (TG) fatty acids and total cholesterol. Subcutaneous fat at
      different sites were sampled at the beginning and the end of deuterium
      administration to measure deuterium incorporation into TG fatty acids. RESULTS:
      Fractional de novo synthesis rate of TG fatty acids in adipose tissue was 0.
      014+/-0.005 and 0.014+/-0.007% in lean and obese Caucasian women, corresponding
      to 2+/-0.7 and 5.6+/-3.2 g (P=0.3) of fatty acids synthesized daily,
      respectively. Plasma TG fatty acids and cholesterol synthesis rates were
      comparable to those reported previously. A pilot study showed that de novo lipid
      synthesis in adipose tissue of obese Pima Indians was also quantitatively minor.
      CONCLUSION: Human adipose tissue, like the liver, does not make a major
      contribution to whole body lipogenesis under eucaloric conditions. A combination
      of deuterated water and isotope ratio mass spectrometry is a useful research tool
      for studying accumulation of de novo synthesized lipids in human adipose tissue.

PMID- 10918546
TI  - Accuracy of the OMRON M4 automatic blood pressure measuring device.
AB  - Despite widespread use of the automatic blood pressure (BP) measuring device
      OMRON M4, there is little formal validation on its accuracy. A study was
      conducted to assess the accuracy of the OMRON M4 compared with the true indirect
      BP measured by mercury sphygmomanometer (MS). A rapid method for the evaluation
      of automatic blood pressure measurement devices (READ) was applied for this
      study. The READ is based on numerous BP measurements at rest and during a
      standardised postural challenge in a small number of subjects who exhibit a wide
      range of BPs. Blood pressure measurements were done in supine position for 10 min
      followed by head-up tilt for 30 min and again supine for 10 min. The automatic
      device (AU) and the MS were connected to one arm-cuff by means of a T connector.
      A stethoscope with dual sets of ear-pieces was used for duplicate MS measurements
      (MS1 and MS2). The MS1, MS2 and AU measurements were taken simultaneously in a
      blinded manner. Three units of the automatic instrument were evaluated. An
      average of 111 measurements per unit were performed, every BP category being
      present in >/=15 MS measurements. The differences between MS1 and MS2
      measurements (DeltaBP: MS1-MS2) were utilized to assess the consistency of true
      indirect BP and the differences between AU and MS measurements (DeltaBP:AU-MS2)
      were utilized to assess the accuracy of the AU. The following characteristics of
      the OMRON M4 were assessed: (1) grade of accuracy, (2) aberration pattern, (3)
      consistency of the aberration-pattern, and (4) correlation between levels of BP
      and DeltaBP: AU-MS. For MS paired readings, 92-100% of systolic and 99-100% of
      diastolic readings fell within 5 mm Hg difference range, that is consistent with
      a British Hypertension Society grade A of both. For AU compared to MS2, 29-64% of
      systolic and 73-94% of diastolic readings fell within 5 mm Hg and 49-86% of
      systolic and 86-99% of diastolic readings fell within 10 mm Hg and the devices
      qualified C, D and C, respectively. All devices exhibited irregular and
      inconsistent aberration patterns, making the design of correction formulas
      impractical. In conclusion, the OMRON M4 device did not meet the requirements of
      the British Hypertension Society and, therefore, cannot be recommended for
      clinical use.

PMID- 10918545
TI  - Should all patients with hypertension have echocardiography?
AB  - The feasibility of echocardiographic determination of left ventricular (LV) mass,
      as well as the advantages that might be gained in some clinical circumstances and
      possible indications are examined in the present review, in relation to the
      recent WHO/ISH. The information obtained with echocardiograms in arterial
      hypertension is an important contribution to risk stratification on an
      epidemiological scale. In clinical practice, under the ascertained condition of a
      good reliability, an echocardiogram should be recommended as part of the initial
      work up when patients meet criteria for not starting therapy (low or mild risk
      WHO-ISH) or in all circumstances in which decision-making might be affected by
      the echocardiographic result. At present, there is not sufficient evidence to
      extend the indication of echocardiography also to patients for whom
      antihypertensive management is already necessitated by identification of high or
      very high risk status.

PMID- 10918547
TI  - How well do office and exercise blood pressures predict sustained hypertension? A
      Dundee Step Test Study.
AB  - Exercise systolic blood pressure (BP) appears to be a better predictor of cardiac
      mortality than casual office BP. We tested whether this could be explained by
      exercise systolic BP being a better predictor of sustained hypertension than
      casual office BP. Exercise systolic BP was measured using the lightweight 3-min
      single stage, submaximal Dundee Step Test in 191 consecutive subjects (102 male,
      age 52 (s.d. 13) years) who were referred to a specialist hypertension clinic for
      assessment. Exercise systolic BP was compared with office BP and daytime
      ambulatory BP (ABP). Sustained hypertension was defined as a mean daytime
      systolic and/or diastolic ABP of >/=140/90 mm Hg. Receiver operating
      characteristic (ROC) curves of exercise systolic BP and office BP in predicting
      sustained hypertension were compared. The positive predictive value of office
      diastolic BP >/=90 mm Hg and office systolic BP >/=140 mm Hg for sustained
      hypertension were 64% and 67% respectively. However, exercise systolic BP >/=180
      mm Hg had a positive predictive value of 76%. Twenty-two percent (42/191) of
      subjects had an exercise systolic BP rise to >/=210 mm Hg, and 93% of this group
      had sustained hypertension on ABP. Whilst exercise systolic BP was a better
      predictor of sustained hypertension using currently recommended office BP
      treatment thresholds, the ROC curves of these indices were not different. In a
      multiple regression analysis, exercise systolic BP was an independent predictor
      of sustained hypertension, accounting for 36% of the variance of daytime systolic
      ABP after adjusting for age, gender and antihypertensive drug treatment. In
      conclusion, exercise systolic BP was a marginally better predictor of sustained
      hypertension than office BP. This may partly explain why exercise systolic BP is
      a potent predictor of cardiac mortality.

PMID- 10918548
TI  - Practice vs ambulatory blood pressure measurement under treatment with ramipril
      (PLUR Study): a randomised, prospective long-term study to evaluate the benefits
      of ABPM in patients on antihypertensive treatment.
AB  - The usefulness of ambulatory blood pressure monitoring (ABPM) vs casual blood
      pressure measurement in the physicians practice (PM) for the routine management
      of patients with hypertension concerning total mortality and morbidity has been
      compared in a prospective, randomised, open multicentre study with a 5-year
      follow-up. The study was performed in general practitioners offices in Germany
      from 1991 to 1997. A total of 1298 patients with essential hypertension were
      included. Cardio- and cerebrovascular events, total mortality/morbidity and drug
      saving effects in hypertensives treated according to two different methods of
      blood pressure measurement were the primary and secondary endpoints of the study.
      A total of 239 patients from group 1 (ABPM, n = 651), and 208 from group 2 (PM, n
      = 647) prematurely discontinued the study. The reason for discontinuation in 55
      of these patients (20 from group 1 and 35 from group 2) was that they reached the
      main endpoint (total mortality/morbidity and cardio- and cerebrovascular events)
      of the study. The difference was statistically significant (P = 0.037) in favour
      of group 1. Cardio- and cerebrovascular events also occurred in a lower number of
      patients (n = 14) in group 1, as compared to group 2 (n = 24). The difference
      however was not significant (P = 0. 097). A difference in a direct drug-saving
      effect could not be observed between the two groups but 22% of the initially
      screened patients were detected with the ABPM to have white coat hypertension and
      thus these patients did not receive antihypertensive treatment.

PMID- 10918549
TI  - Familial aggregation of blood pressure: a population-based family study in
      eastern Finland.
AB  - Blood pressure (BP) levels in the Finnish population are amongst the highest in
      the world, despite favourable changes at the national level in the past two
      decades. The study evaluates the familial aggregation of BP and the association
      of some environmental factors to the familial aggregation of BP as a primary
      epidemiological approach of the genetics of hypertension in a sample of families
      with young offspring from eastern Finland. Offspring aged 15 years were examined
      between 1996 and 1997 and their biological parents were examined between 1993 and
      1994. A total of 224 children were invited, 184 families participated, from which
      144 were included in the analysis with complete data. Systolic (SBP), diastolic
      (DBP) and mean (MAP) arterial BPs were the main outcome measurements. After the
      offspring's gender and body mass index (BMI) and the parent's age and BMI were
      controlled for, the mother/offspring correlation of SBP and the father/offspring
      correlation of MAP were statistically significant (r = 0.18, P = 0.039, n = 134
      and r = 0.20, P = 0.048, n = 99, respectively). The additional adjustment for the
      parent's education and family history of acute myocardial infarction did not
      change these results. There was a higher proportion of offspring in the highest
      quartile of SBP and MAP when the mother had a history of hypertension (OR = 3.4,
      95% CI = 1.4-8.5, n = 139, and OR = 2.6, 95% CI = 1.0-6.5, n = 139,
      respectively). The study confirmed the familial aggregation of BP. The consistent
      BP association between the mother and the offspring may indicate the key role of
      the mother in the primary prevention of hypertension.

PMID- 10918550
TI  - Antihypertensive treatment modulates the association between the D/I ACE gene
      polymorphism and left ventricular hypertrophy: a meta-analysis.
AB  - This meta-analysis attempted to derive pooled estimates for the putative
      association between echocardiographic or electrocardiographic left ventricular
      hypertrophy and the deletion/insertion (D/I) polymorphism of the angiotensin-I
      converting enzyme. Case-control studies were combined, using the Mantel and
      Haenszel approach. Joint P-values for continuous variables were calculated by
      Stouffer's method. Continuous measurements of left ventricular mass, which were
      reported in different units, were expressed on a percentage scale using the
      within-study mean of the II genotype as the denominator. The computerised
      database used for this analysis, included 28 reports with an overall sample size
      of 6638 subjects. The prevalence of the D allele was significantly lower in
      Japanese (37.2%) than in Caucasians (56.2%). A funnel plot including 12 case
      control studies (4094 subjects) suggested that no publication bias was present.
      Overall, left ventricular hypertrophy was not associated with the D allele.
      Compared with the II genotype, the excess risks of left ventricular hypertrophy
      associated with DD and DI genotypes were only 14% (95% CI: 0.92-1.42; P = 0.23)
      and 5% (95% CI: 0.87-1.28; P = 0.61), respectively. However, the sensitivity
      analysis showed that in untreated hypertensive patients the DD genotype, compared
      with II homozygozity, was associated with a 192% (P = 0.002) higher risk of left
      ventricular hypertrophy. If left ventricular mass was analysed as a continuous
      trait across 23 studies (5438 subjects), overall no association with the D/I
      polymorphism was present. However, if untreated hypertensive patients were
      analysed separately, echocardiographic left ventricular mass was on average 10.1%
      (95% CI: 4.8-15.5%; P = 0.001) higher in DDhomozygotes than in the II reference
      group. Thus, in untreated hypertensive patients, in case-control studies as well
      as association studies, the D allele behaved as a marker for left ventricular
      hypertrophy. These findings support the hypothesis that the enhanced ACE activity
      associated with the D allele may promote left ventricular hypertrophy if a
      pathophysiologic process causing this disorder, remains unopposed by treatment.

PMID- 10918551
TI  - Urinary acid-base excretion in normotensives and hypertensives of african origin.
AB  - Abnormalities in acid-base regulation have previously been reported both in
      hypertensive humans and animals and a link between abnormalities in renal sodium
      handling and acid excretion may be particularly important in black hypertensives.
      The objectives of this study were to compare indices of urinary acid excretion
      (urinary pH, ammonium and titratable acid excretion) between normotensives and
      hypertensive people of African origin. Measurements were carried out in 86 black
      individuals of African origin in a case-control design (19 normotensive; 67
      hypertensive). Of these, 17 normotensive and 17 patients with essential
      hypertension were matched for age, sex and weight. Group comparisons were carried
      out by unpaired t-tests or two-way analysis of variance and group values are
      given as means +/- s.d. Urinary pH was significantly higher in the hypertensives
      both in the unmatched groups and in the matched groups. In the 17 matched pairs:
      urinary pH in the hypertensive individuals was 6.36 +/- 0.54 and 5.84 +/- 0. 53
      in the normotensives, respectively; P = 0.007. Additionally, urinary titratable
      acidity was significantly lower in the hypertensives than in the normotensives
      (25.4 +/- 13.7 vs16.7 +/- 10. 7 mmol/24 h; P = 0.047) but there were no
      significant differences in urinary ammonium excretion. The mechanisms for the
      apparent reduction in acid excretion in the hypertensives is not clear but these
      results highlight the possibility that hypertension in blacks is associated with
      abnormalities of renal sodium and hydrogen exchange with compensatory increases
      in renal ammonium production.

PMID- 10918553
TI  - Cardiac involvement in pheochromocytoma.
AB  - We report the details of a 40-year-old farmer, a cigarette smoker, who was
      admitted with general malaise, nausea, vomiting, upper abdominal pain, with ST
      elevation on ECG suggestive of an acute anterolateral myocardial infarction. He
      was treated with nitrates, heparin, beta-blockade and angiotensin-converting
      enzyme (ACE) inhibitors. Because of the presence of some blood while vomiting no
      thrombolysis was given and abdominal echography was performed. This revealed a
      nodular mass at the right adrenal gland. Urinary catecholamines and abdominal
      magnetic resonance imaging confirmed the suspected diagnosis of pheochromocytoma.
      Before adrenectomy, a coronary angiography under alpha blocker therapy was
      performed, which demonstrated no significant coronary artery disease, although
      the patient showed ST-elevations on ECG. Pathological examination of the adrenal
      tumor was compatible with a diagnosis of pheochromocytoma. Postoperatively
      urinary catecholamines dropped dramatically, and the ECG normalised slowly over
      time. After 8 months the patient is still well. Blood pressure is well controlled
      with no antihypertensive drugs and exercise testing shows no evidence of
      myocardial ischaemia.

PMID- 10918552
TI  - Renal kallikrein excretion: role of ethnicity, gender, environment, and genetic
      risk of hypertension.
AB  - BACKGROUND AND OBJECTIVE: Alterations in renal kallikrein excretion are well
      described in hypertension, and kallikrein excretion may predict risk of
      developing hypertension, but kallikrein excretion has not been directly compared
      across several ethnic strata, nor have the effects of ethnicity, gender,
      environment, and genetic risk of hypertension been simultaneously considered as
      determinants of kallikrein. METHODS: We investigated determinants of kallikrein
      excretion in a cross-section of n = 204 normotensive subjects stratified by
      ethnicity (119 Caucasian, 33 African-American, 52 Asian), gender (109 men, 95
      women), environment (spontaneous electrolyte intake/excretion), and heredity
      (genetic risk (family history) of hypertension). Results were interpreted by
      analysis of variance (with Bonferroni post hoc comparison corrections), analysis
      of covariance, multiple linear regression, and maximum likelihood. RESULTS:
      Urinary kallikrein activity varied substantially (F = 5.30, P = 0.006) across the
      three ethnic groups, with African-American values approximately 50% lower than
      Caucasian (P = 0.005) or Asian (P = 0.02). Ethnicity and gender (T = 3.24, P =
      0.001) had independent effects on kallikrein, with women excreting approximately
      50% more kallikrein than men, regardless of ethnicity. Subjects at genetic risk
      of hypertension were over-represented (P = 0.048) in the lower stratum of a
      bimodal distribution of kallikrein excretion (chi-square = 29.6, P < 0.001).
      Potassium excretion was diminished in African-Americans (P < 0.001 to P = 0.002),
      and in a multivariate analysis, potassium excretion was the strongest correlate
      of kallikrein excretion (T = 4.10, P = 0.0001). In a subset of Caucasian and
      African-American individuals, African-Americans exhibited diminished excretion of
      not only kallikrein and potassium, but also aldosterone (P = 0.003), suggesting a
      mechanistic link between potassium and kallikrein excretion in their ethnic
      variations. CONCLUSIONS: Kallikrein excretion is influenced by several
      independent determinants, both hereditary (gender, ethnicity, and genetic risk of
      hypertension) and environmental (potassium intake and excretion). Ethnicity and
      environment may interact uniquely to influence kallikrein, as demonstrated by the
      case of African-Americans with diminutions of both kallikrein and potassium
      excretion. These results suggest a mechanism whereby kallikrein excretion is
      diminished in African-Americans, as well as therapeutic strategies to correct
      this deficiency. Finally, the identified determinants of kallikrein excretion
      will require analytic adjustment during genetic studies of this 'intermediate
      phenotype' in hypertension. Journal of Human Hypertension (2000) 14, 461-468

PMID- 10918554
TI  - Effect of lacidipine on blood pressure, vasoactive hormones, and haemorheology in
      elderly patients with essential hypertension.

PMID- 10918556
TI  - Structured review of enamel erosion literature (1980-1998): a critical appraisal
      of experimental, clinical and review publications.
AB  - OBJECTIVE: To attain an objective account of the methods to measure enamel
      erosion used in 1980-1998 publications, a structured review of the literature was
      undertaken. METHODS: Inclusion and exclusion criteria were applied to 731
      clinical/experimental research and review reports. Eighty-five included papers
      were subsequently rated according to 'hierarchy of evidence' guidelines to assess
      the strength of the report's design and the relevance of the evidence to
      replicating enamel erosion in vivo in humans. Scores were assigned to rate each
      aspect in the guidelines. RESULTS: A total of 16 clinical, 13 review and 56
      experimental papers were assessed; 36.4% were published during 1996-1998.
      Excluding reviews, 16 papers were qualitative and 56 quantitative; 51 used human
      enamel. Our classification yielded nine groups of methods (five scoring systems
      and 26 measurement techniques). CTFPHE (Can Med Assoc J 1992; 147: 443) grading
      of research reports indicated that 2.8% provided evidence grade I; 20.8%, grade
      IIa; 63.9%, grade III; and 12.5%, grade IV. CONCLUSIONS: There has been a
      consistent increase in the body of knowledge. The overall quality of publications
      has not substantially changed over time. Experimental studies were more often
      quantitative, and quantitative studies had better research designs. No single
      group of research methods had obviously superior research designs.

PMID- 10918557
TI  - Paraneoplastic pemphigus: a review of the literature.
AB  - Paraneoplastic pemphigus is a relatively rare but highly significant acquired
      mucocutaneous disorder. The condition typically presents in patients with
      previously diagnosed lymphoreticular disease, primarily malignancies (non
      Hodgkin's lymphoma; chronic lymphocytic leukemia). Multiple sites of involvement
      are common, with the skin affected by a polymorphous eruption that includes
      lichenoid plaques as well as bullae. The oral lesions occur in all cases and
      present as painful widespread shallow ulcers with hemorrhagic crusting of the
      lips. Conjunctival involvement is also seen and may result in scarring. Pulmonary
      lesions are an ominous sign. Histopathologically, intraepithelial and
      subepithelial clefting associated with interface dermatitis are seen. A variety
      of autoantibodies directed against desmoplakins and desmogleins can be identified
      with immunoprecipitation studies. Treatment with immunosuppressive agents may
      result in some resolution of the disease, but the prognosis for paraneoplastic
      pemphigus is considered to be poor.

PMID- 10918558
TI  - Cytotoxicity of methyl methacrylate (MMA) and related compounds and their
      interaction with dipalmitoylphosphatidylcholine (DPPC) liposomes as a model for
      biomembranes.
AB  - OBJECTIVE: To clarify the potential mechanism of action of methyl methacrylate
      (MMA) and related compounds to membranes of living cells, compared with their
      interaction with dipalmitoylphosphatidylcholine (DPPC) liposomes as a model for
      biological membranes. MATERIALS AND METHODS: For (meth)acrylates, MMA, ethyl
      acrylate(EA), n-butyl acrylate (BA) and n-butyl methacrylate (BMA) and for living
      cells, primary human gingival fibroblast (HGF), human submandibular gland
      adenocarcinoma cell line (HSG) and human erythrocytes were used. The
      physicochemical changes in DPPC liposomes induced by (meth)acrylates were studied
      using differential scanning calorimetry (DSC) and nuclear magnetic resonance
      spectroscopy (NMR). RESULTS: Cytotoxicity decreased as follows: BA > BMA > EA >
      MMA. Changes in phase transition properties (temperature Tm, enthalpy delta H and
      Height/Half-Height Width (H/HHW) of DSC peak were decreased as follows: BA > EA >
      MMA. BMA enhanced H/HHW and increased Tm slightly. NMR-shielding effect decreased
      as follows: BMA > MMA > BA, EA. CONCLUSION: BA and BMA exhibited large
      cytotoxicity and high DPPC-interaction due to their lipophilicity, compared to EA
      or MMA. MMA showed little cytotoxicity and small changes in DPPC liposomes,
      whereas BA showed large cytotoxicity and large changes in the liposomes
      characterized by the membrane disturbance. Haemolytic activity and cytotoxicity
      of acrylates were higher than those of methacrylates. The physico-chemical
      properties (Log P or Q sigma) of (meth)acrylates affect the lipid bilayer in
      biological membranes.

PMID- 10918559
TI  - Cytokine mRNA expression in the labial salivary glands of healthy volunteers.
AB  - OBJECTIVE: To examine the cytokine profile in minor salivary glands of healthy
      volunteers and examine differential cytokine production from acinar and ductal
      tissues. STUDY DESIGN: Acinar and ductal elements were isolated by a cell
      specific micro-dissection technique from frozen 8 microns sections of minor
      salivary glands from healthy volunteers. Reverse transcriptase-polymerase chain
      reaction (RT-PCR) and Southern hybridization using 32P-labeled cytokine gene
      specific probes were utilized to detect cytokine mRNA. mRNA transcripts for the
      Th1 cytokines (IL-2, TNF-alpha, and IFN-gamma), Th2 cytokines (IL-4, IL-6, and IL
      10), TGF-beta, actin, and CD3 delta were analyzed in acini, ducts and total
      tissue sections of minor salivary glands of six healthy controls. RESULTS: Actin,
      TGF beta and TNF alpha was present in 6/6 acinar, 6/6 ductal, and 6/6 total
      section samples. IFN gamma was present in 2/6 acinar, 3/6 ductal, and 6/6 total
      samples. IL-2 was found in 3/6 acinar, 3/6 ductal and 5/6 total sections. IL-6
      was found in 1/6 acinar, 0/6 ductal, and 5/6 total sections. IL-10 was found in
      3/6 acinar, 3/6 ductal, and 5/6 total sections. IL-4 was present in 0/6 acinar,
      0/6 ductal and 1/6 total samples. CD3 delta was present in 6/6 acinar, 5/6 ductal
      and 6/6 total sections. CONCLUSIONS: These results demonstrate abundant
      expression of cytokines in healthy minor salivary glands. The production of these
      cytokines in healthy tissues demonstrates a likely role of supporting normal
      cellular function.

PMID- 10918560
TI  - Surface properties of lactobacilli isolated from healthy subjects.
AB  - OBJECTIVE: Lactobacilli are considered cariogenic micro-organisms. As oral
      species of lactobacilli have not been thoroughly described, the aim of this work
      was to isolated and identify these organisms from teeth, tongue, saliva and gum
      of healthy patients and to describe some of their surface properties. SUBJECTS:
      Forty-four subjects from Tucuman, Argentina, with D, d and M, m indices equal to
      0. MATERIALS AND METHODS: Samples were obtained from different areas of the oral
      cavity. Microorganisms were cultured in lactobacilli selected media (LBS) and
      identified morphologically and biochemically. Hydrophobicity was analysed by
      partition in organic solvents, acidity by affinity with chloroform and basicity
      with ethyl acetate (MATH method), aggregation and coaggregation in presence of
      (NH4)2SO4, and haemagglutination with ABO erythrocytes in microplates. RESULTS:
      Eighty-five lactobacilli were isolated; 29.4% were homofermenter, 44.7%
      facultative heterofermenter and 25.9% obligate heterofermenter. Predominant
      species were L. fermentum, L. plantarum, L. salivarius, and L. rhamnosus. Most of
      the strains showed moderate to high hydrophobicity and demonstrated high acid and
      basic surface charges with almost 40% showing salt aggregation. Few strains
      haemagglutinated. CONCLUSIONS: A variety of Lactobacillus species were isolated
      from healthy mouths, some of whom showed adhesion-related properties such as high
      hydrophobicity and charged surfaces. Probable mechanisms related to the
      ecological behaviour of lactobacilli in the oral cavity are discussed.

PMID- 10918561
TI  - Integrin expression in oral hairy leukoplakia and normal tongue epithelium.
AB  - OBJECTIVE: To describe the expression of integrins in the epithelium of oral
      hairy leukoplakia (HL) and compare to that of normal lateral tongue epithelium.
      MATERIALS AND METHODS: Immunohistochemistry to identify integrins (alpha 2, alpha
      3, alpha 5, alpha 6, alpha v, beta 1) was performed, using a standard biotin
      streptavidin-peroxidase technique on five clinically and histologically confirmed
      frozen biopsy specimens of HL and five normal lateral tongue control tissues.
      RESULTS: Expression of integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 was
      seen both in HL epithelium and in normal control tissue. alpha 5 expression was
      not seen in HL or in control tissue epithelium. alpha 2 and alpha 3 were
      expressed mainly in the basal and suprabasal layers; alpha 6 expression was most
      intense on the basal surface of the basal cells, alpha v was expressed in the
      basal and suprabasal layers with more expression seen in the higher
      differentiated cell layers than the other integrins. beta 1 expression was seen
      in the basal and suprabasal layers only. No apparent difference between HL and
      normal oral mucosa was noted in the staining pattern of the various integrins.
      CONCLUSION: Integrins alpha 2, alpha 3, alpha 6, alpha v, beta 1 are expressed in
      HL and the expression pattern is not different from that of normal oral mucosa.
      alpha 5 is not expressed in HL or in normal oral epithelium.

PMID- 10918563
TI  - Cowden's syndrome (multiple hamartoma and neoplasia syndrome): diagnostic
      dilemmas in three cases.
AB  - Cowden's syndrome is a multisystem disease inherited as an autosomal dominant
      trait with incomplete penetrance and variable expression. The disease has typical
      oral manifestations which often precede more systemic involvement, and the dental
      professional is therefore well placed to institute a regime of regular checks to
      ensure early treatment of any neoplasms which may occur. However, since not all
      of the classical signs are present in all patients, diagnosis may be difficult.
      The case report of a patient with most of the features of Cowden's syndrome is
      presented and features compared with two other possible cases.

PMID- 10918562
TI  - Role of vitamins C and E as chemopreventive agents in the hamster cheek pouch
      treated with the oral carcinogen-DMBA.
AB  - OBJECTIVE: To evaluate the role of vitamins C and E as chemopreventive agents in
      oral carcinogenesis by optical and ultrastructural studies. MATERIALS AND
      METHODS: The cheek pouch of male hamsters was treated with the oral carcinogen,
      dimethylbenz(a)anthracene (DMBA), to induce multiple tumour formation. Vitamins C
      and E were applied either singly or in combination as a chemopreventive agent.
      Paraffin and resin-embedded sections of the hamster cheek pouch were studied
      optically and ultrastructurally. RESULTS: The epithelium of control hamsters
      showed hyperorthokeratosis and parakeratosis, but did not develop well
      differentiated squamous cell carcinoma (WDSCC). Ninety percent of the animals
      treated with DMBA alone showed WDSCC while 10% of the animals developed
      papillomas. There was also a marked increase in the number of cells undergoing
      mitosis in this group. A reduction in the yield (1.1 tumour/animal) and rate 60
      80% of squamous cell carcinomas but not of papillomas (2.0 papillomas/animal) was
      observed in groups VI-VIII treated with DMBA and vitamins C and E singly or in
      combination as compared to those of DMBA only. In animals treated with DMBA plus
      vitamins C and E, statistical significant decrease in the number of animals with
      tumours and mitotic basal cells was observed when compared with the DMBA treated
      group. Control animals showed normal ultrastructural morphology while tumour
      bearing animals showed basal lamina in a discontinuous, fragmented, broken and
      diffused basement membrane, with diminished lamina densa, fewer hemidesmosomes
      and invagination of the basal cell cytoplasmic processes in the subepithelium.
      CONCLUSION: These results indicate that vitamin E singly or in combination with
      vitamin C plays a role in the inhibition of tumour cell growth.

PMID- 10918564
TI  - Cysticercosis of the oral cavity: report of seven cases.
AB  - Cysticercosis is a condition in which a human acts as the intermediate host of
      the pork tapeworm Taenia solium. Although cysticercosis is a common disease in
      some regions of the world and can occur in any body site, oral lesions are rare.
      This paper reviews the natural history of the disease and reports on seven cases
      of oral cysticercosis.

PMID- 10918565
TI  - A case of Burkitt's lymphoma that presented initially with resorption of alveolar
      bone.
AB  - A 16-year-old male was evaluated for a 1-month history of alveolar bone
      resorption, which had been treated with endodontics by a neighborhood dentist.
      Intraoral examination showed slight gingival swelling and teeth mobility.
      However, no tumor mass was seen. The panoramic image showed resorption of
      alveolar bone and loss of teeth lamina dura. Because he complained of general
      fatigue, he was introduced to the internist. Biopsies of gingiva and bone marrow
      aspiration revealed a massive proliferation of lymphoblasts expressing CD10, 19,
      20 and HLA-DR antigens on the surface. Their karyotypes were abnormal; 46, XY, t
      (8;14) (q24;q32). Accordingly, he was diagnosed as Burkitt's lymphoma, and
      received intensive chemotherapy which relieved his symptoms and decreased his
      tumor. However, his disease soon became refractory to chemotherapy, and he died
      11 weeks after the onset.

PMID- 10918566
TI  - A case of palatal Wegener's granulomatosis.
AB  - The purpose of this article is to describe the clinical and microscopic findings
      of oral lesions of Wegener's granulomatosis (WG) in a patient who presented with
      a limited form of the disease. cANCA estimation remains the definitive diagnostic
      test for WG but we recommend that both the immunofluorescent and ELISA forms of
      analysis are performed, and care should be exercised in the interpretation of
      results. Because both serological tests may be negative in a significant
      proportion of cases, a tissue biopsy is required to help establish the diagnosis.
      The biopsy needs to be sufficiently deep to include the granulomatous
      inflammation required for diagnosis, and multiple histological levels on the
      tissue may be needed to identify vasculitis.

PMID- 10918567
TI  - Envelope-dependent transactivation by the retroviral oncoprotein v-Rel is
      required for efficient malignant transformation of chicken spleen cells.
AB  - The retroviral oncoprotein v-Rel is a chimeric protein that has 11 helper virus
      derived Envelope (Env) amino acids (aa) at its N terminus. Within these N
      terminal Env aa of v-Rel there are three aa substitutions compared to the Rev-A
      helper virus Env. These aa substitutions have previously been shown to impart a
      number of unique properties onto v-Rel, including increased transforming and
      transactivating ability. In this study, we have analysed the sequence
      requirements for the Env aa to influence several properties of v-Rel. Phe
      residues at aa 3 and 9 are critical for an N-terminal transactivation function of
      v-Rel, and the analysis of several Env mutants demonstrates that transactivation
      ability parallels the transforming ability of v-Rel. Substitutions of
      conservative aa, such as leucine and tyrosine, for Phe 3 and 9 are tolerated for
      transactivation in chicken embryo fibroblasts and for transformation of chicken
      spleen cells. In contrast, the substitution of 10 Phe residues at the N terminus
      of v-Rel does not enable transactivation, indicating that a distinct structure
      surrounding Phe-3 and Phe-9 is essential for v-Rel function. We also show that
      the addition of the v-Rel Env aa to the N terminus of human c-Rel can enable it
      to activate transcription. Taken together, these results indicate that Phe
      residues at positions 3 and 9 have been selected for their ability to enhance the
      oncogenicity of v-Rel by increasing its ability to activate transcription.

PMID- 10918569
TI  - PTEN expression is reduced in a subset of sporadic thyroid carcinomas: evidence
      that PTEN-growth suppressing activity in thyroid cancer cells mediated by
      p27kip1.
AB  - The dual-specificity phosphatase PTEN/MMAC1/TEP1 has recently been identified as
      the tumor suppressor gene most frequently mutated and/or deleted in human tumors.
      Germline mutations of PTEN give rise to Cowden Disease (CD), an autosomal
      dominantly-inherited cancer syndrome which predisposes to increased risk of
      developing breast and thyroid tumors. However, PTEN mutations have rarely been
      detected in sporadic thyroid carcinomas. In this study, we confirm that PTEN
      mutations in sporadic thyroid cancer are infrequent as we found one point
      mutation and one heterozygous deletion of PTEN gene in 26 tumors and eight cell
      lines screened. However, we report that PTEN expression is reduced both at the
      mRNA and at the protein level - in five out of eight tumor-derived cell lines and
      in 24 out of 61 primary tumors. In most cases, decreased PTEN expression is
      correlated with increased phosphorylation of the PTEN-regulated protein kinase
      Akt/PKB. Moreover, we demonstrate that PTEN may act as a suppressor of thyroid
      cancerogenesis as the constitutive re-expression of PTEN into two different
      thyroid tumor cell lines markedly inhibits cell growth. PTEN-dependent inhibition
      of BrdU incorporation is accompanied by enhanced expression of the cyclin
      dependent kinase inhibitor p27kip1 and can be overcome by simultaneous co
      transfection of an excess p27kip1 antisense plasmid. Accordingly, in a subset of
      thyroid primary carcinomas and tumor-derived cell lines, a striking correlation
      between PTEN expression and the level of p27kip1 protein was observed. In
      conclusion, our findings demonstrate that inactivation of PTEN may play a role in
      the development of sporadic thyroid carcinomas and that one key target of PTEN
      suppressor activity is represented by the cyclin-dependent kinase inhibitor
      p27kip1.

PMID- 10918568
TI  - Spontaneous development of drug resistance: mismatch repair and p53 defects in
      resistance to cisplatin in human tumor cells.
AB  - The contributions of defective mismatch repair and mutated p53 to cisplatin
      resistance of human tumor cells were analysed. Mismatch repair defects were not
      associated with a predictable degree of resistance among several tumor cell
      lines. Repair defective variants of the A2780 ovarian carcinoma cell line which
      were isolated by selection for a methylation tolerant phenotype and did not
      express the hMLH1 mismatch repair protein, were highly resistant to cisplatin.
      Their cisplatin resistance was not a simple consequence of the mismatch repair
      defect. They were members of a drug-naive subpopulation of A2780 in which a
      silent hMLH1 gene accompanies a mutated p53. Two complementary approaches
      indicated that each defect contributes to cisplatin resistance independently and
      to a different extent. Firstly, separate introduction of a p53 defect into A2780
      cells significantly increased their cisplatin resistance; defective hMLH1
      provided less extensive protection. Secondly, azadeoxycytidine reactivation of
      the silent hMLH1 gene or expression of a transfected hMLH1 cDNA sensitized the
      doubly hMLH1/p53 deficient cells only slightly to cisplatin. Both approaches
      indicate that defective p53 status is a major determinant of cisplatin resistance
      and defective mismatch repair is a minor, and independent, contributor. The data
      have implications for the development of intrinsic cisplatin resistance.

PMID- 10918570
TI  - Regulation of fibronectin matrix assembly by activated Ras in transformed cells.
AB  - Fibronectin extracellular matrix plays a critical role in the microenvironment of
      cells. Loss of this matrix frequently accompanies oncogenic transformation,
      allowing changes in cell growth, morphology, and tissue organization. The HT1080
      human fibrosarcoma cell line is deficient in formation of fibronectin matrix
      fibrils but assembly can be induced by the glucocorticoid dexamethasone. Here we
      show that fibronectin assembly can also be restored by stimulation of alpha5beta1
      integrin with activating antibody or with Mn2+ suggesting that integrin activity
      is reduced in these cells. While dexamethasone promoted actin stress fiber
      formation, actin filaments remained cortical following Mn2+ treatment showing
      that the dexamethasone effect is not due solely to cytoskeletal changes. HT1080
      cells have one activated allele of N-ras and PD98059 inhibition of signaling from
      Ras through ERK increased fibronectin matrix accumulation. Conversely, the p38
      MAP kinase inhibitor SB203580 blocked induction of matrix and increased ERK
      phosphorylation. Thus, two MAP kinase pathways contribute to the control of
      integrin-mediated fibronectin assembly. ERK activity and fibronectin assembly
      were linked in three different ras-transformed cell lines but not in SV40- or RSV
      transformed cells indicating that oncogenic Ras uses a distinct mechanism to down
      regulate cell-fibronectin interactions.

PMID- 10918571
TI  - Shp-2 mediates v-Src-induced morphological changes and activation of the anti
      apoptotic protein kinase Akt.
AB  - The protein-tyrosine phosphatase Shp-2 is a positive modulator of the Ras/mitogen
      activated protein kinase pathway and a putative substrate of the transforming non
      receptor tyrosine kinase v-Src. To characterize the role of Shp-2 in cellular
      transformation and signaling by v-Src, we expressed v-Src in normal and Shp-2
      deficient mouse embryo fibroblasts. Expression of Shp-2 was found to be necessary
      for morphological transformation by v-Src: Shp-2+/+ cells became rounded or
      spindly upon v-Src expression, whereas Shp-2-deficient cells remained relatively
      flat. v-Src-induced reorganization of the actin cytoskeleton and the formation of
      podosomes were compromised in Shp-2-deficient cells. Shp-2 deficiency also
      reduced v-Src-induced activation of the anti-apoptotic protein kinase Akt. The
      reduced activation of Akt in Shp-2-deficient cells correlated with a reduction in
      the association of the p85 regulatory subunit of PI3-kinase with the adapter
      protein Cbl. Activation of PI3-kinase by v-Src may be mediated by the association
      of the adapter protein Cbl with the p85 subunit. Since activation of Akt is
      dependent on PI3-kinase, this suggests that the effect of Shp-2 on Akt activation
      may be mediated, at least in part, by its effects on the interaction between PI3
      kinase and Cbl. The defect in activation of the Akt survival pathway also
      correlated with enhanced sensitivity of Shp-2-deficient cells to an apoptosis
      inducing agent. These results implicate Shp-2 in v-Src-induced cytoskeletal
      reorganization and activation of the Akt cell survival pathway.

PMID- 10918572
TI  - Unique carboxyl-terminal sequences of wild type and alternatively spliced variant
      forms of transforming growth factor-alpha precursors mediate specific
      interactions with ErbB4 and ErbB2.
AB  - We have previously reported that the human transforming growth factor-alpha (TGF
      alpha) gene encodes three forms of TGF-alpha precursors, designated wild type
      (WT), variant I (VaI), and variant II (VaII), derived from alternative splicing.
      The two carboxyl-terminal valine residues of WT are replaced by 5 (GCRLY) or 4
      (ATLG) amino acids in VaI or VaII, respectively. When overexpressed in Chinese
      hamster ovary (CHO) cells, VaI and ValI, but not WT, support autonomous growth.
      We detected tyrosine phosphorylation of ErbB2 in the absence of serum, in CHO
      cells expressing WT, VaI, or VaII, but not in mock transfectants. These
      observations prompted us to investigate possible interactions between the ErbBs
      and the TGF-alpha precursors in CHO cells. All TGF-alpha precursors were found to
      co-immunoprecipitate with the ErbBs, but with different specificity. WT co
      immunoprecipitated with ErbB4, but not with ErbB1, ErbB2, or ErbB3. VaI and VaII
      co-immunoprecipitated with ErbB2, but not with ErbB1, ErbB3, or ErbB4. Confocal
      fluorescent microscopy analysis demonstrated that WT, VaI, and VaII all
      distribute equally to the cell surface while, as expected, a WT mutant lacking
      the two C-terminal valine residues does not. Point and deletion mutants involving
      the unique carboxyl-terminal residues of WT, VaI and VaII, indicated that the
      interactions between the three TGF-alpha precursors and the ErbBs were mediated
      by their carboxyl-terminal regions, which constitute distinct protein-binding
      motifs. A chimera of the intracellular domain of WT TGF-alpha linked to exogenous
      transmembrane and extracellular domains retained both the cell surface
      distribution and the specific interaction with ErbB4 of full-length WT,
      confirming that this interaction is mediated by the C-terminus of the TGF-alpha
      precursor. While interactions of WT and variant TGF-alpha with the ErbBs all
      result in ErbB2 activation, they produce different biological consequences,
      suggesting that the various TGF-alpha precursors differentially modulate ErbB
      signaling.

PMID- 10918573
TI  - The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus
      distal to D4Mit64.
AB  - The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during
      a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice.
      Here, we demonstrate that the Mom1AKR allele consists of two genetic components.
      These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1
      resistance modifier has now been tested with several transgenic lines. A second
      region, distal to Pla2g2a, has also been identified using fine structure
      recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to
      tumorigenesis in the small intestine and a very robust resistance in the large
      intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is
      dosage-dependent, a finding that is consistent with our observation that Pla2g2a
      is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier
      demonstrate a modest tumor resistance that is confined to the small intestine.
      Thus, the phenotypes of these two modifier loci are complementary, both in their
      quantitative and regional effects. The additive effects and tight linkage of
      these modifiers may have been necessary for the initial identification of the
      Mom1 region.

PMID- 10918575
TI  - Genetic dissection of c-myc apoptotic pathways.
AB  - All biological functions mediated by the c-myc oncoprotein require an intact
      transactivation domain (TAD). We compared TAD mutants for their ability to
      promote apoptosis of 32D myeloid cells in response to interleukin-3 (IL-3)
      deprivation and exposure to chemotherapeutic drugs, and to activate ornithine
      decarboxylase, an endogenous c-myc target. Different sub-regions of the TAD were
      required to mediate each function. cDNA microarrays were then used to identify
      multiple c-myc-regulated transcripts, some of which were also modulated by IL-3
      or cytotoxic drugs, as well as by specific sub-regions of the TAD. Several of the
      c-myc-regulated transcripts had also been previously identified as targets for
      IFN-gamma. The functional consequences of their deregulation were manifested by a
      marked sensitivity of c-myc-overexpressing cells to IFN-gamma-mediated apoptosis.
      Our results establish that several well-characterized functions of c-myc are
      separable and correlate with the expression of a novel group of target genes,
      some of which also mediate the apoptotic action of IFN-gamma.

PMID- 10918574
TI  - Cooperative induction of mammary tumorigenesis by TGFalpha and Wnts.
AB  - We previously reported that multiparous WAP-TGFalpha transgenic mice develop
      mammary gland carcinomas with complete incidence. TGFalpha-induced tumors appear
      stochastically and with relatively long latency, indicating an additional
      requirement for other genetic alterations. To identify genes that cooperate with
      TGFalpha in mammary tumorigenesis, we used a retroviral insertion approach
      featuring a cloned and infectious hybrid MMTV (C3H/Mtv-1; (Shackleford and
      Varmus, 1988)). Tumor latency was decreased approximately 30% in MMTV-infected
      WAP-TGFalpha transgenic animals compared to noninfected transgenic controls, and
      > 30% of the corresponding tumors displayed evidence of integrated C3H/Mtv-1 DNA.
      PCR-based analyses of DNAs from two virus-infected, transgenic tumors revealed
      integration of hybrid MMTV in 3' untranslated exons of the Wnt-1 or Wnt-3
      oncogenes. Moreover, Northern blots confirmed dramatic induction of Wnt-1 or Wnt
      3 transcripts in the respective tumors, indicating that MMTV integration resulted
      in activated expression of these genes. Semiquantitative RT-PCR analyses showed
      that overexpression of Wnt-1 or Wnt-3 was a common occurrence in MMTV-infected
      WAP-TGFalpha tumors, and some noninfected WAP-TGFalpha tumors also showed
      evidence of elevated Wnt-3 transcripts. Collectively, these results reveal
      cooperative induction of mammary gland tumorigenesis by simultaneous deregulation
      of EGF-like (TGFalpha) and Wnt growth factors.

PMID- 10918576
TI  - Unmasking of phosphorylation-sensitive epitopes on p53 and Mdm2 by a simple
      Western-phosphatase procedure.
AB  - Monoclonal antibodies are widely used for the assessment of protein expression
      levels, protein-protein interactions and protein localization. Phosphorylation of
      one or more residues within an epitope recognized by a particular antibody may
      compromise the ability of that antibody to bind the target protein. Inhibition of
      immunoreactivity by phosphorylation has been reported for many antibody/protein
      pairs. Here we describe a simple convenient protocol for assessing the effect of
      phosphorylation on immunoreactivity, employing phosphatase treatment of Western
      blotted membranes. The efficacy of this protocol is demonstrated for p53 and for
      Mdm2. This method is useful for obtaining more uniform protein quantification, as
      well as for rapid assessment of changes in the extent of phosphorylation within a
      given epitope in response to defined signals.

PMID- 10918577
TI  - The c-Abl tyrosine kinase contributes to the transient activation of MAP kinase
      in cells plated on fibronectin.
AB  - Previous work showed that integrin stimulation triggers activation of the c-Abl
      tyrosine kinase and its transient localization to focal adhesions. We now report
      that plating cells on fibronectin triggers association of Grb2 with c-Abl,
      suggesting possible involvement of c-Abl with integrin activation of the MAP
      kinase pathway. Expression of a kinase-defective c-Abl specifically inhibited the
      transient induction of Erk2 activity following cell adhesion. Together with the
      known ability of activated, oncogenic forms of c-Abl to activate Ras and the MAP
      kinase pathway, these data suggest that c-Abl contributes to the integrin
      induction of MAP kinase activity.

PMID- 10918578
TI  - Distinct pattern of expression of differentiation and growth-related genes in
      squamous cell carcinomas of the head and neck revealed by the use of laser
      capture microdissection and cDNA arrays.
AB  - Although risk factors for squamous cell carcinomas of the head and neck (HNSCC)
      are well recognized, very little is known about the molecular mechanisms
      responsible for this malignancy. Furthermore, the ability to investigate gene
      expression profiles at different stages of tumor progression is usually limited
      by the remarkable heterogeneity of these neoplastic lesions. Here, we show the
      successful use of laser capture microdissection (LCM) to procure specific cell
      populations. The 5000 cells from representative sets of HNSCC and their matching
      normal tissues are sufficient to extract RNA of high integrity for the synthesis
      of labeled amplified cDNA probes which can then be hybridized to these membranes
      arrayed with known human cancer-related cDNAs. Furthermore, when compared to
      normal tissues, we demonstrate a consistent decrease in expression of
      differentiation markers such as cytokeratins, and an increase in the expression
      of a number of signal transducing and cell cycle regulatory molecules, as well as
      growth and angiogenic factors and tissue degrading proteases. Unexpectedly, we
      also found that most HNSCC overexpress members of the wnt and notch growth and
      differentiation regulatory system, thus suggesting that the wnt and notch
      pathways may contribute in squamous cell carcinogenesis. This experimental
      approach may facilitate the identification candidate markers for the early
      detection of preneoplastic lesions, as well as novel targets for pharmacological
      intervention in this disease.

PMID- 10918579
TI  - Survivin initiates cell cycle entry by the competitive interaction with
      Cdk4/p16(INK4a) and Cdk2/cyclin E complex activation.
AB  - Survivin is observed uniquely in tumor cells and developmental cells, which
      undergo either inappropriate or programmed cell growth. In the current study, we
      investigated the influence of Survivin on cell cycle. Overexpression of Survivin
      resulted in accelerated S phase shift, resistance to G1 arrest, and activated
      Cdk2/Cyclin E complex leading Rb phosphorylation. In addition, nuclear
      translocation of Survivin followed by an interaction with Cdk4 was detected.
      Interestingly, Survivin nuclear translocation coincided with S phase shift, and
      prevention of nuclear transport suppressed Survivin nuclear translocation and S
      phase shift. Further, we also observed that Survivin competitively interacted
      with the Cdk4/p16(INK4a) complex in a cell free system and in vivo. These results
      suggest that Survivin initiates the cell cycle entry as a result of nuclear
      translocation followed by an interaction with Cdk4.

PMID- 10918580
TI  - Differential transcriptional regulation of the monocyte-chemoattractant protein-1
      (MCP-1) gene in tumorigenic and non-tumorigenic HPV 18 positive cells: the role
      of the chromatin structure and AP-1 composition.
AB  - The expression of the monocyte-chemoattractant-protein-1 (MCP-1) is closely
      linked with a non-tumorigenic phenotype in somatic cell hybrids made between the
      human papillomavirus type 18 (HPV 18) positive cervical carcinoma cell line HeLa
      and normal human fibroblasts. In contrast, MCP-1 transcription is absent in
      tumorigenic segregants derived from the same hybrids or in parental HeLa cells.
      Selectivity of MCP-1 transcription, which is regulated at the level of initiation
      of transcription, is mainly based on differences in the location and extension of
      DNAse I-hypersensitive regions (DHSR) at both ends of the gene. While TNF-alpha
      only moderately increases the sensitivity of pre-existing 5'-DHSRs, a 3'-end DHSR
      became strongly induced exclusively in non-malignant hybrids. DNA sequencing
      showed that the 3'-DHSR coincides with an additional AP-1 site located
      approximately 600 bp downstream of the polyadenylation site. Analyses of AP-1
      composition revealed that MCP-1 is only expressed in those cells where jun-family
      members were mainly heterodimerized with the fos-related protein fra-1. In
      contrast, in tumorigenic cells the 1: 1 ratio between jun and fra-1 is disturbed
      and the MCP-1 gene is no longer expressed. Hence, alterations in the
      heterodimerization pattern of AP-1 and its selective accessibility to opened
      chromatin may represent a novel regulatory pathway in the regulation of
      chemokines in malignant and non-malignant HPV-positive cells.

PMID- 10918581
TI  - Cooperative transformation of 32D cells by the combined expression of IRS-1 and V
      Ha-Ras.
AB  - 32D cells expressing v-Ha-Ras fail to show a transformed phenotype. Since Ras
      requires an active IGF-1R for transformation of fibroblasts, we asked whether
      expression of IRS-1 or Shc (two of the major substrates of the IGF-1R) could co
      operate with oncogenic Ras in transforming 32D cells. We find that IRS-1, but not
      Shc, in combination with v-Ha-Ras generates a fully transformed phenotype in 32D
      cells. 32D cells expressing both IRS-1 and v-Ha-Ras (32D/IRS1/Ras) survive and
      proliferate in the absence of IL-3, do not undergo granulocytic differentiation
      in the presence of G-CSF and form tumors in nu/nu and syngeneic mice. In
      contrast, 32D cells expressing singly IRS-1 or v-Ha-Ras exhibit only a block in
      differentiation capacity. Over-expression of Shc proteins, by itself, promotes
      differentiation of 32D cells. Concomitant expression of IRS-1 and v-Ha-Ras
      synergistically phosphorylates ERK-1 and ERK-2 whereas a MEK inhibitor rapidly
      induces death of 32D/IRS1/Ras transformed cells. Furthermore, transformed
      32D/IRS1/Ras cells display high levels of PI3-K activation and undergo rapid
      apoptosis when exposed to PI3-K inhibitors. The data indicate that: (1) a fully
      transformed phenotype in 32D cells is generated when a block in differentiation
      (v-Ha-Ras) is coupled with another differentiation block (IRS-1); (2) PI3-K and
      MAPK activity are required for the survival of transformed cells; (3) the signals
      generated by IRS-1 and oncogenic Ras converge on ERK and PI3-K resulting in high
      levels of activation.

PMID- 10918582
TI  - Caveolin-1 is regulated by c-myc and suppresses c-myc-induced apoptosis.
AB  - Recent data indicating that overexpression of caveolin-1 as well as c-myc are
      relatively common features of advanced prostate cancer prompted us to test for
      potential cooperative interactions between caveolin-1 and c-myc that would be
      consistent with malignant progression. We used the well-characterized Rat1AmycERT
      cells to show that the caveolin-1 gene is down-regulated at the level of
      transcription by c-myc. By maintaining relatively high levels of caveolin-1 with
      an adenoviral vector or in stably transfected clones we show that caveolin-1 can
      suppress c-myc-induced apoptosis. Further we established human prostate cancer
      cell lines with the mycER construct and show that clones with increased caveolin
      1 are more resistant to myc-induced apoptosis and have increased capacity for
      growth in soft agar when c-myc is activated.

PMID- 10918584
TI  - Normal and c-Myc-promoted human keratinocyte differentiation both occur via a
      novel cell cycle involving cellular growth and endoreplication.
AB  - The relationship between cell cycle and differentiation in human keratinocytes is
      poorly understood. It is believed that keratinocytes suppress DNA replication and
      cell cycle arrest in G0 before they initiate terminal differentiation. However, a
      temporal separation between both events has not been established. Moreover, c-Myc
      promotes keratinocyte differentiation without causing cell cycle arrest. To
      address these paradoxes we have analysed cell cycle control during normal and c
      Myc-promoted differentiation. Continuous activation of c-Myc or initiation of
      terminal differentiation results in a block of G2/M, cellular growth,
      endoreplication and polyploidy. Keratinocytes abandon G1, continue replicating
      DNA as they differentiate terminally and become polyploid. In fact, simply
      blocking mitosis with nocodazole resulted in increased cell size, terminal
      differentiation and endoreplication. This indicates that terminal differentiation
      associates with defective cell cycle progression and provides a novel insight
      into c-Myc biology.

PMID- 10918583
TI  - Mlx, a new Max-like bHLHZip family member: the center stage of a novel
      transcription factors regulatory pathway?
AB  - The Myc proto-oncogene family members have been identified as the cellular
      homologs of the transforming oncogene of avian retroviruses. They encode central
      regulators of mammalian cell proliferation and apoptosis, and they associate with
      the bHLHZip protein Max to bind specific DNA sequences and regulate the
      expression of genes important for cell cycle progression. The other family
      members, Mad1, Mxi1, Mad3, Mad4 and Rox (Mnt) antagonize their activities. The
      Mads and Rox compete with Myc in heterodimerizing with Max and in binding to the
      same specific target sequences. These Mads:Max and Rox:Max dimers repress
      transcription through binding to the mSIN3 corepressor protein and by tethering
      histone deacetylase-containing complexes to the DNA. In a screen for Rox
      interactors we isolated Mlx, a bHLHZip protein previously identified in a screen
      for Mad1 interactors. In the present work we extend the known dimerization
      partners of Mlx by demonstrating its ability to interact with Rox. Moreover, we
      show that contrary to previous reports Mlx is able to homodimerize and to bind E
      box sequences at low concentration levels. The possible role of Mlx in an
      emerging regulatory pathway and acting parallel to the Max driven network is
      discussed.

PMID- 10918585
TI  - STAT3-mediated differentiation and survival and of myeloid cells in response to
      granulocyte colony-stimulating factor: role for the cyclin-dependent kinase
      inhibitor p27(Kip1).
AB  - The signal transducer and activator of transcription (STAT) proteins have been
      implicated in cytokine-regulated proliferation, differentiation and cell
      survival. Granulocyte colony-stimulating factor (G-CSF), a regulator of
      granulocytic differentiation, induces a robust and sustained activation of STAT3.
      Here, we show that introduction of dominant negative (DN) forms of STAT3
      interferes with G-CSF-induced differentiation and survival in murine 32D cells. G
      CSF induces expression of the cyclin-dependent kinase (cdk) inhibitor p27(KiP1)
      (but not p21(CiP1)), which is completely blocked by DN-STAT3. The ability of
      tyrosine-to-phenylalanine substitution mutants of the G-CSF receptor to activate
      STAT3 strongly correlated with their capacity to induce p27 expression and their
      ability to mediate differentiation and survival, suggesting a causal relationship
      between STAT3 activation, p27 expression and the observed cellular responses. We
      identified a putative STAT binding site in the promoter region of p27 that showed
      both STAT3 binding in electrophoretic mobility shift assays and functional
      activity in luciferase reporter assays. Finally, we studied G-CSF-induced
      responses in primary bone marrow and spleen cells of p27-deficient mice. Compared
      with wild-type, myeloid progenitors from p27-deficient mice showed significantly
      increased proliferation and reduced differentiation in response to G-CSF. These
      findings indicate that STAT3 controls myeloid differentiation, at least partly,
      via upregulation of p27(Kip1).

PMID- 10918586
TI  - A Drosophila analogue of v-Cbl is a dominant-negative oncoprotein in vivo.
AB  - Cells rely on the ability to receive and interpret external signals to regulate
      growth, differentiation, and death. Positive transduction of these signals to the
      cytoplasm and nucleus has been extensively characterized, and genetic studies in
      Drosophila have made major contributions to the understanding of these pathways.
      Less well understood, but equally important, are the mechanisms underlying signal
      down-regulation. Here we report biochemical and genetic characterization of the
      Drosophila homologue of c-Cbl, a negative regulator of signal transduction with
      ubiquitin-protein ligase activity. A new isoform of D-Cbl, D-CblL, has been
      identified that contains SH3-binding and UBA domains previously reported to be
      absent. Genetic analysis demonstrates that Dv-cbl, analogous to the mammalian v
      cbl oncogene, is a dominant negative mutation able to enhance signalling from the
      Drosophila Egfr and cooperate with activating mutations in the sevenless pathway
      to produce melanotic tumours. In addition, our data show genetic and biochemical
      links between D-Cbl and proteins involved in endocytosis and ubiquitination,
      suggesting that v-Cbl may exert its oncogenic effect by enhancing receptor
      signalling as a consequence of suppressing receptor endocytosis.

PMID- 10918587
TI  - Transformation and Stat activation by derivatives of FGFR1, FGFR3, and FGFR4.
AB  - The fibroblast growth factor receptor (FGFR) family members mediate a number of
      important cellular processes, and are mutated or overexpressed in several forms
      of human cancer. Mutation of Lys650-->Glu in the activation loop of the FGFR3
      kinase domain causes the lethal human skeletal disorder thanatophoric dysplasia
      type II (TDII) and is also found in patients with multiple myeloma, bladder and
      cervical carcinomas. This mutation leads to constitutive activation of FGFR3. To
      compare the signaling activity of FGFR family members, this activating mutation
      was generated in FGFR1, FGFR3, and FGFR4. We show that the kinase domains of
      FGFR1, FGFR3, and FGFR4 containing the activation loop mutation, when targeted to
      the plasma membrane by a myristylation signal, can transform NIH3T3 cells and
      induce neurite outgrowth in PC12 cells. Phosphorylation of Shp2, PLC-gamma, and
      MAPK was also stimulated by all three 'TDII-like' FGFR derivatives. Additionally,
      activation of Stat1 and Stat3 was observed in cells expressing the activated FGFR
      derivatives. Finally, we demonstrate that FGFR1, FGFR3, and FGFR4 derivatives can
      stimulate PI-3 kinase activity. Our comparison of these activated receptor
      derivatives reveals a significant overlap in the panel of effector proteins used
      to mediate downstream signals. This also represents the first demonstration that
      activation of FGFR4, in addition to FGFR1 and FGFR3, can induce cellular
      transformation. Moreover, our results suggest that Stat activation by FGFRs is
      important in their ability to act as oncogenes.

PMID- 10918588
TI  - Substrate specificity of the p53-associated 3'-5' exonuclease.
AB  - p53 exhibits 3'-5' exonuclease activity and the significance of this biochemical
      function is currently not defined. In order to gain information about the
      potential role(s) of this exonuclease activity, recombinant and wild-type human
      p53 was examined for excision of nucleotides from defined synthetic DNA
      substrates. p53 removes nucleotides threefold faster from single-strand DNA than
      from DNA duplexes, exhibits a 1.5-fold preference for 3'-terminals of DNA that
      contain a single nucleotide mispair (mismatch) as compared to correctly paired
      DNA and efficiently excises nucleotides from 3'-ends of blunt and cohesive
      (staggered) DNA double-strand breaks. The p53 exonuclease is predominantly non
      processive on DNA which is 17 nucleotides long (or shorter) and processive on the
      longer 30-mers. The processivity of nucleotide excision is decreased in the
      presence of 50 mM potassium phosphate and eliminated when full-length p53 is
      replaced with the core domain, comprised of amino acids 82-292. Photoaffinity
      labeling indicates that (1) p53 monomers, rather than dimers, bind to single
      strand forms of these oligomers; (2) complexes between p53 and 30-mers are more
      stable than those formed with 17-mers. The stability of these complexes
      determines processivity during nucleotide removal and modulates the 3'-5'
      exonuclease activity of p53. The relevance of substrate specificity of the p53
      exonuclease to DNA repair is discussed.

PMID- 10918590
TI  - Initiation of adult myelopoiesis can occur in the absence of c-Myb whereas
      subsequent development is strictly dependent on the transcription factor.
AB  - The c-Myb transcriptional regulator is crucial to the development and functioning
      of haemopoietic cells, so much so that mouse embryos homozygous for an
      inactivated c-myb allele die from anaemia at about day 15 of gestation. By
      analysing c-myb(-/-) chimaeras we show that no mature cells of any lymphoid or
      myeloid lineage can be detected in adult haemopoietic tissues. This demonstrates
      that the effects of c-myb ablation on haemopoiesis are cell autonomous and
      correlates with an absence in the c-myb(-/-) foetal liver of uni- and
      multilineage CFUs. Indeed, CFU assays performed on E8.5 yolk sac cells revealed
      that haemopoietic progenitors are already defective at this stage. However,
      although cells expressing high levels of c-Kit were absent, we could detect a
      high proportion of CD34+CD45+ cells in the c-myb(-/-) foetal liver. Examination
      of chimaeric embryos revealed that c-myb(-/-) donor-derived CD34+/Kit+ cells,
      representing committed definitive progenitors, initially populated the foetal
      liver, but are unable to expand like wild type progenitors. Our results showing
      no megakaryocytic CFUs and a reduction in the absolute numbers of megakaryocytes
      in the c-myb(-/-) foetal liver also refute early suggestions that
      megakaryopoiesis is unaffected by the absence of c-Myb.

PMID- 10918589
TI  - A genetic screen to identify genes that rescue the slow growth phenotype of c-myc
      null fibroblasts.
AB  - The c-myc gene is frequently over-expressed in human cancers and is involved in
      regulation of proliferation, differentiation and apoptosis. c-Myc is a
      transcription factor that acts primarily by regulating the expression of other
      genes. However, it has been very difficult to identify bona fide c-Myc target
      genes that explain its diverse biological activities. The recent generation of c
      myc deficient Rat1A fibroblasts with a profound and stable growth defect provides
      a new system to search for genes that can substitute for c-myc in proliferation.
      In this study, we have attempted to identify genes that rescue the slow growth
      phenotype of c-myc null cells through introduction of a series of potent cell
      cycle regulatory genes and several retroviral cDNA expression libraries. None of
      the candidate genes tested, including SV40 T-antigen and adenovirus E1A, caused
      reversal of the c-myc null growth defect. Furthermore, extensive screens with
      high-complexity retroviral cDNA libraries from three different tissue sources
      revealed that only c-myc and N-myc rescued the c-myc null slow-growth phenotype.
      Our data support the notion that there are no functional equivalents of the myc
      family of proto-oncogenes and also suggest that there are no c-Myc-activated
      genes that alone can substitute for c-Myc in control of cell proliferation.

PMID- 10918591
TI  - In vitro differentiation of c-myb(-/-) ES cells reveals that the colony forming
      capacity of unilineage macrophage precursors and myeloid progenitor commitment
      are c-Myb independent.
AB  - Mice homozygous for an inactivated c-myb allele exhibit embryonic (primitive)
      blood formation but die at about day 15 of gestation because of a failure to
      generate adult (definitive) haemopoiesis. Recently, it has been shown that
      commitment to definitive haemopoiesis does occur in vivo, but that some point in
      the subsequent development towards the differentiated lineages is compromised.
      Here we have asked whether it is possible to demonstrate this same distinction
      between the development of primitive and definitive haemopoiesis during the in
      vitro differentiation of c-myb null ES cells, and whether this can be used to
      define more precisely at which developmental stage the absence of c-Myb blocks
      the adult haemopoietic lineages. We investigated the kinetics of progenitor
      formation and commitment to differentiation using a combination of colony forming
      assays and analysis of RNA and surface antigen expression. Primitive unilineage
      macrophage and erythroid precursor commitment could develop in the absence of c
      Myb. No precursors characteristic of definitive haemopoiesis were detected;
      nevertheless, we could show the expression of a programme of transcription and
      surface antigens which is consistent with the appearance of definitive
      progenitors blocked at an early multipotential stage.

PMID- 10918592
TI  - The retinoblastoma gene family members pRB and p107 coactivate the AP-1-dependent
      mouse tissue factor promoter in fibroblasts.
AB  - Serum-stimulation of quiescent mouse fibroblasts results in transcriptional
      activation of tissue factor (TF), the cellular initiator of blood coagulation.
      This requires the rapid entry of c-Fos into specific AP-1 DNA-binding complexes
      and can be strongly inhibited by the adenovirus EIA 12S gene product. In this
      study, we utilized a panel of E1A mutants deficient in cellular protein binding
      to analyse the molecular basis for EIA inhibition of a minimal, c-Fos-dependent
      TF promoter/ reporter construct in mouse AKR-2B fibroblasts. Mutations which
      impaired binding of the retinoblastoma tumor suppressor protein family members
      pRB, p107, and p130 relieved E1A-mediated inhibition of transcription in response
      to serum-stimulation or c-Fos overexpression. Inhibition was restricted to the G0
      to G1 transition, consistent with the specificity of E1A for hypophosphorylated
      forms of RB proteins. Although E1A mutants deficient in CBP/p300 binding retained
      the ability to inhibit TF transcription, deletion of the amino-terminal portion
      of the CBP/p300 interaction domain was required to permit rescue of TF promoter
      activity by coexpression of pRB. Moreover, ectopic p107 could effectively
      substitute for pRB in relieving E1A-mediated repression. In primary mouse embryo
      fibroblasts, activity of the minimal AP-1-dependent TF promoter was suppressed in
      Rb(-/-) cells compared to parallel Rb(+/-) and Rb(+/+) transfectants. Ectopic
      expression of either pRB or p107 markedly enhanced TF promoter activity in Rb(-/
      ) fibroblasts. Collectively, these data imply that pRB and p107 can cooperate
      with c-Fos to activate TF gene transcription in fibroblasts and suggest a
      requirement for another, as yet unidentified, E1A-binding protein.

PMID- 10918593
TI  - TRAIL-induced apoptosis of thyroid cancer cells: potential for therapeutic
      intervention.
AB  - To determine whether the apoptotic machinery of thyroid cancer cells is
      functional and could be activated for tumoricidal purposes, we examined the
      apoptosis induced by the cytokines TNF-alpha, Fas and TRAIL in thyroid cancer
      cell lines, NPA and SW579. Interestingly, out of these cytokines, only TRAIL was
      able to trigger significant apoptosis. The tumoricidal effect of TRAIL was
      further enhanced by CHX, suggesting the presence of CHX-sensitive inhibitor(s) of
      apoptosis in these thyroid cancer cell lines. The anti-apoptotic proteins like
      FLAME-1, Bcl-2 and Bcl-xL are believed to be such CHX-sensitive inhibitors in
      various types of cancer cells. We, however, provide the evidence using NPA and
      SW579 cell lines that these proteins were not affected by the CHX treatment in
      thyroid cancer cells. The apoptosis of thyroid cancer cells was mediated by the
      classical activation of caspases that in turn activated the DNA Fragmentation
      Factor (DFF-45). To elucidate the role of individual caspases in TRAIL-mediated
      apoptosis, the inhibitory effects of several general and specific tetrapeptide
      caspase inhibitors were studied. The inhibitors of caspase-1, -6, -8, and -9 as
      well as general upstream inhibitors of apoptosis could dramatically inhibit TRAIL
      induced apoptosis in thyroid cancer cells. Caspase-2 and -3 inhibitors, on the
      other hand, had no significant effect. When the cells were treated with either
      agonistic Fas antibody (CH11) or TNF-alpha, no apoptotic changes were observed.
      The apoptosis induced by agonistic Fas Ab could be seen only after a prolonged
      exposure (24 h) to CHX, whereas TNF-alpha had no effect even in the presence of
      CHX. The efficacy of TRAIL was also tested on other types of thyroid cancer cells
      like ARO, FRO (anaplastic carcinoma) and TPC-1 (papillary carcinoma) and compared
      to that triggered by other death inducing cytokines FasL and TNF-alpha. Again
      TRAIL was more potent in triggering apoptosis than Fas and TNF-alpha. Since TRAIL
      is effective in selectively killing thyroid tumor cells without affecting normal
      thyrocytes and also does not cause organ toxicity and inflammation in vivo, its
      potential for the treatment of thyroid cancer seems very promising.

PMID- 10918594
TI  - IFN-beta induces serine phosphorylation of Stat-1 in Ewing's sarcoma cells and
      mediates apoptosis via induction of IRF-1 and activation of caspase-7.
AB  - Four human cell lines derived from Ewing's sarcoma, EW-7, EW-1, COH and ORS, were
      investigated to establish the effects of human recombinant interferon-alpha2a and
      human recombinant interferon-beta on cell proliferation and apoptosis. All four
      cell lines were much more sensitive to the antiproliferative effects of IFN-beta
      than of IFN-alpha. Analysis of the early signals triggered by IFN-alpha and IFN
      beta demonstrated that the two IFNs were similarly effective in inducing tyrosine
      phosphorylation of the Jak-1 and Tyk-2 kinases and the transcription factors Stat
      1 and Stat-2. Interestingly, an additional rapid phosphorylation of Stat-1 on
      serine was observed after IFN-beta treatment, with concomitant activation of p38
      mitogen-activated protein kinase. In these cells, Stat-1 Ser727 phosphorylation
      in response to IFN-beta was found to be impaired by p38 MAPkinase inhibitor
      (SB203580). IFN-beta induced the formation of the Interferon Stimulated Gene
      Factor 3 complex more efficiently than IFN-alpha, as well as sustained induction
      of IRF-1, which may account for its greater induction of 2'5'oligo(A)synthetase
      and greater inhibition of cell proliferation. IFN-beta, but not IFN-alpha,
      induced apoptosis in wild-type p53 EW-7 and COH cell lines, but not in the
      mutated p53 EW-1 or ORS cell lines. The apoptosis induced by IFN-beta in EW-7 and
      COH cell lines appeared to be mediated by IRF-1 and involved the activation of
      caspase-7. Ectopic expression of IRF-1 induced apoptosis in all four cell lines
      which correlated with the activation of caspase-7 and with the downregulation of
      the Bcl-2 oncoprotein, as observed for IFN-beta-induced apoptosis in parental EW
      7 and COH cell lines.

PMID- 10918595
TI  - Hepatitis B virus-X protein upregulates the expression of p21waf1/cip1 and
      prolongs G1-->S transition via a p53-independent pathway in human hepatoma cells.
AB  - Progression through the cell cycle is controlled by the induction of cyclins and
      activation of cognate cyclin-dependent kinases. The human hepatitis B virus-X
      (HBV-X) protein functions in gene expression alterations, in the sensitization of
      cells to apoptotic killing and deregulates cell growth arrest in certain cancer
      cell types. We have pursued the mechanism of growth arrest in Hep3B cells, a p53
      mutant human hepatocellular carcinoma (HCC) cell line. In stable or transient HBV
      X transformed Hep3B cells, HBV-X increased protein and mRNA levels of the cyclin
      dependent kinase inhibitor (CDKI) p21(waf1/cip1) increased binding of
      p21(waf1/cip1) with cyclin-dependent kinase 2 (CDK2), markedly inhibited cyclin E
      and CDK2 associated phosphorylation of histone H1 and induced the activation of a
      p21 promoter reporter construct. By using p21 promoter deletion constructs, the
      HBV-X responsive element was mapped to a region between -1185 and -1482, relative
      to the transcription start site. Promoter mutation analysis indicated that the
      HBV-X responsive site coincides with the ets factor binding sites. These data
      indicate that in human hepatocellular carcinoma cells, HBV-X can circumvent the
      loss of p53 functions and induces critical downstream regulatory events leading
      to transcriptional activation of p21(waf1/cip1). As a consequence, there is an
      increased chance of acquisition of mutations which can enhance the genesis of
      hepatomas. Our results also emphasize the chemotherapeutic potential of
      p21(waf1/cip1) inhibitors, particularly in the HBV-X infected hepatoma which
      lacks functional p53.

PMID- 10918596
TI  - p53-dependent apoptosis is regulated by a C-terminally alternatively spliced form
      of murine p53.
AB  - It is now well accepted that the p53 C-terminus plays a central role in
      controlling the activity of the wild-type molecule. In our previous studies, we
      observed that a C-terminally altered p53 protein (p53AS), generated by an
      alternative spliced p53 mRNA, induces an attenuated p53-dependent apoptosis,
      compared to that induced by the regularly spliced form (p53RS). In the present
      study we analysed the interrelationships between these two physiological variants
      of wild-type p53, and found that in cells co-expressing both forms, in contrast
      to the expected additive effect on the induction of apoptosis, p53AS inhibits
      apoptosis induced by p53RS. This inhibitory effect is specific for p53-dependent
      apoptosis and was not evident in a p53-independent apoptotic pathway induced by
      growth factor deprivation. Furthermore, the expression of p53AS in transiently
      transfected cells caused both inhibition of apoptosis and inhibition of the p53RS
      dependent transactivation of a number of p53 target genes. These results suggest
      that expression of an alternatively spliced p53 form may serve as an additional
      level in controlling the complexity of p53 function by the C-terminal domain.

PMID- 10918597
TI  - The c-MYC allele that is translocated into the IgH locus undergoes constitutive
      hypermutation in a Burkitt's lymphoma line.
AB  - Burkitt's lymphomas harbour chromosomal translocations bringing c-MYC into the
      vicinity of one of the immunoglobulin gene loci. Point mutations have been
      described within c-MYC in several Burkitt's lymphomas and it has been proposed
      that translocation into the Ig loci might have transformed c-MYC into a substrate
      for the antibody hypermutation mechanism. Here we test this hypothesis by
      exploiting a Burkitt's lymphoma line (Ramos) that we have previously shown to
      hypermutate its immunoglobulin genes constitutively. We find that, during in
      vitro culture, Ramos mutates the c-MYC allele that is translocated into the IgH
      locus whilst leaving the untranslocated c-MYC and other control genes essentially
      unaffected. The mutations are introduced downstream of the c-MYC transcription
      start with the pattern of substitutions being characteristic of the antibody
      hypermutation mechanism; the mutation frequency is 2-3-fold lower than for the
      endogenous functional IgH allele. Thus chromosomal translocations involving the
      Ig loci may not only contribute to transformation by deregulating oncogene
      expression but could also act by potentiating subsequent oncogene hypermutation.

PMID- 10918598
TI  - Cooperation between AP1 and PEA3 sites within the progression elevated gene-3
      (PEG-3) promoter regulate basal and differential expression of PEG-3 during
      progression of the oncogenic phenotype in transformed rat embryo cells.
AB  - Cancer is a progressive disease in which a tumor cell temporally develops
      qualitatively new transformation related phenotypes or a further elaboration of
      existing transformation associated properties. Subtraction hybridization
      identified a novel gene associated with transformation progression in mutant
      adenovirus type 5, H5ts125, transformed rat embryo cells, progression elevated
      gene-3 (PEG-3). To define the mechanism by which expression of PEG-3 is enhanced
      as a function of cancer progression a 5'-flanking promoter region of
      approximately 2.0-kb, PEG-Prom, was isolated, cloned and characterized. The full
      length and various mutated regions of the PEG-Prom were linked to a luciferase
      reporter construct and evaluated for promoter activity during cancer progression.
      These assays demonstrate a requirement for AP1 and PEA3 sites adjacent to the
      TATA box region of PEG-3 in mediating basal promoter activity and the enhanced
      expression of PEG-3 in progressed H5ts125-transformed rat embryo cells. An
      involvement of AP1 and PEA3 in PEG-3 regulation was also confirmed by
      electrophoretic mobility shift assays (EMSA) and transfection studies with cJun
      and PEA3 expression vectors. Our findings document the importance of both AP1 and
      PEA3 transcription factors in mediating basal and elevated expression of PEG-3 in
      H5ts125-transformed rat embryo cells displaying an aggressive and progressed
      cancer phenotype.

PMID- 10918600
TI  - Accommodating haploinsufficient tumor suppressor genes in Knudson's model.

PMID- 10918599
TI  - Identification of E2F-3B, an alternative form of E2F-3 lacking a conserved N
      terminal region.
AB  - We have identified a novel form of the full-length E2F-3 protein that we term E2F
      3B. In contrast to full-length E2F-3, which is expressed only at the G1/S
      boundary, E2F-3B is detected throughout the cell cycle with peak levels in GO
      where it is associated with Rb. Transfection and in vitro translation experiments
      demonstrate that a protein identical to E2F-3B in size and iso-electric point is
      produced from the E2F-3 mRNA via the use of an alternative translational start
      site. This alternative initiation codon was mapped by mutagenesis to codon 102,
      an ACG codon. Mutation of the ACG codon at position 102 abolished E2F-3B
      expression, whereas the conversion of ACG 102 to a consensus ATG led to the
      expression of a protein indistinguishable from E2F-3B. Given these results, E2F
      3B is missing 101 N-terminal amino acids relative to full-length E2F-3. This
      region includes a moderately conserved sequence of unknown function that is
      present only in the growth-promoting E2F family members, including E2F-1, 2 and
      full-length E2F-3. These observations make E2F-3B the first example of an E2F
      gene giving rise to two different protein species and also suggest that E2F-3 and
      E2F-3B may have opposing roles in cell cycle control.

PMID- 10918601
TI  - High level expression of deltaN-p63: a mechanism for the inactivation of p53 in
      undifferentiated nasopharyngeal carcinoma (NPC)?
AB  - Undifferentiated nasopharyngeal carcinoma (NPC) is an epithelial malignancy that
      is consistently associated with Epstein-Barr virus (EBV) but which very rarely
      has p53 gene mutations in primary tumours. Since the tumour suppressor p53 is
      mutated in most human cancers or the wild type protein is inactivated in a
      significant number of the remainder, here we have investigated cellular factors
      that could compromise p53 function in primary NPC. Twenty-five primary tumours
      were judged to carry only wild type p53 by SSCP analysis of all exons and
      sequence determination of exons 4-9. Only one tumour was found to express
      significant levels of hMdm2 and in 24/25 there were no detectable mutations or
      deletions in exons 1beta and 2 of the p14(ARF) gene. However,
      immunohistochemistry consistently revealed that all the tumour cells express
      substantial amounts of the p53-related protein p63. Semi-quantitative RT-PCR
      analysis of mRNA from tumour biopsies showed that the dominant species expressed
      was invariably the truncated deltaN-isotype. Since this can block p53-mediated
      transactivation, it is potentially a dominant-negative isoform. In normal
      nasopharyngeal epithelium the distribution of p63 was restricted to the
      proliferating basal and suprabasal layers. We suggest that deltaN-p63 is a good
      candidate as a suppressor of wild type p53 function in these tumours and also
      that it may prove to be a valuable diagnostic marker for undifferentiated NPC.

PMID- 10918602
TI  - A novel type of mutation in the cysteine rich domain of the RET receptor causes
      ligand independent activation.
AB  - Multiple endocrine neoplasia type 2A (MEN 2A) is a dominantly inherited cancer
      syndrome, which involves the triad of MTC, pheochromocytoma, and
      hyperparathyroidism. Missense mutations in one of six cysteine codons in the
      extracellular cysteine-rich domain of the RET proto-oncogene predispose to this
      disease. These mutations cause ligand-independent constitutive activation of the
      tyrosine kinase receptor by the formation of disulfide-bonded homodimers. We
      examined a different type of mutation, which results in an additional cysteine in
      the cysteine rich domain. A duplication of 9 bp in the first case resulted in an
      insertion of three amino acids between codon 633 and 634. In the second case a 12
      bp duplication in exon 11 results in four additional amino acids between codon
      634 and 635. Here we demonstrate that an additional cysteine causes a ligand
      independent dimerization of the RET receptor in transfected NIH3T3 cells, which
      results in an activation of the intracellular tyrosine kinase.

PMID- 10918603
TI  - The human myoepithelial cell displays a multifaceted anti-angiogenic phenotype.
AB  - Human myoepithelial cells which surround ducts and acini of certain organs such
      as the breast form a natural border separating epithelial cells from stromal
      angiogenesis. Myoepithelial cell lines (HMS-1-6), derived from diverse benign
      myoepithelial tumors, all constitutively express high levels of active angiogenic
      inhibitors which include TIMP-1, thrombospondin-1 and soluble bFGF receptors but
      very low levels of angiogenic factors. These myoepithelial cell lines inhibit
      endothelial cell chemotaxis and proliferation. These myoepithelial cell lines
      sense hypoxia, respond to low O2 tension by increased HIF-1 alpha but with only a
      minimal increase in VEGF and iNOS steady state mRNA levels. Their corresponding
      xenografts (HMS-X-6X) grow very slowly compared to their non-myoepithelial
      carcinomatous counterparts and accumulate an abundant extracellular matrix devoid
      of angiogenesis but containing bound angiogenic inhibitors. These myoepithelial
      xenografts exhibit only minimal hypoxia but extensive necrosis in comparison to
      their non-myoepithelial xenograft counterparts. These former xenografts inhibit
      local and systemic tumor-induced angiogenesis and metastasis presumably from
      their matrix-bound and released circulating angiogenic inhibitors. These
      observations collectively support the hypothesis that the human myoepithelial
      cell (even when transformed) is a natural suppressor of angiogenesis. Oncogene
      (2000) 19, 3449 - 3459

PMID- 10918604
TI  - Heregulin selectively upregulates vascular endothelial growth factor secretion in
      cancer cells and stimulates angiogenesis.
AB  - The interaction between the erbB tyrosine kinase receptors and their ligands
      plays an important role in tumor growth via the regulation of autocrine and
      paracrine loops. We report the effect of heregulin beta1, the ligand for erbB-3
      and erbB-4 receptors, on the regulation of vascular endothelial growth factor
      (VEGF) expression, using a panel of breast and lung cancer cell lines with
      constitutive erbB-2 overexpression or engineered to stably overexpress the erbB-2
      receptor. We demonstrate that heregulin beta1 induces VEGF secretion in most
      cancer cell lines, while no significant effect was observed in normal human
      mammary and bronchial primary cells. Overexpression of erbB-2 receptor results in
      induction of the basal level of VEGF and exposure to heregulin further enhances
      VEGF secretion. This is associated with increased VEGF mRNA expression. In
      contrast, VEGF induction is significantly decreased in a T47D cell line where
      erbB-2 is functionally inactivated. Conditioned media from heregulin-treated
      cancer cells, but not from normal cells, stimulates endothelial cell
      proliferation; this paracrine stimulation is inhibited by co-exposure to a
      specific VEGF neutralizing antibody. Furthermore, heregulin-mediated angiogenesis
      is observed in the in vivo CAM assay. This study reports the first evidence of
      VEGF regulation by heregulin in cancer cells. Oncogene (2000) 19, 3460 - 3469

PMID- 10918605
TI  - Expression of the vascular endothelial growth factor gene is inhibited by p73.
AB  - Recently, p73, a new member of the p53 family, has been cloned and mapped to
      chromosome 1p36, a region that is frequently deleted in a variety of human
      cancers. p73 can activate p53-responsive promoters and induce apoptosis when
      overexpressed in certain p53-deficient tumor cells. In contrast to p53, analysis
      of the p73 gene in several human solid tumors did not reveal loss of p73
      expression or mutations in the p73 gene. However, transcriptional silencing of
      the p73 gene by hypermethylation of a CpG island was observed in several
      leukemias and lymphomas. These lymphoid neoplasms also show increased expression
      of vascular endothelial growth factor (VEGF), an endothelial cell-specific
      mitogen and a key mediator of angiogenesis. To evaluate a possible relationship
      between p73 status and VEGF expression, we have studied the effect of ectopically
      expressed p73 on the regulation of the VEGF gene. Our results demonstrate that
      p73 can down-regulate endogenous VEGF gene expression on mRNA and protein level.
      This effect is mediated by transcriptional repression of the VEGF promoter and
      involves the promoter region -85 to -50 bp, containing a cluster of Sp 1 binding
      sites. Our results suggest a regulatory role for p73 in tumor angiogenesis.
      Oncogene (2000) 19, 3470 - 3476

PMID- 10918607
TI  - RNA polymerase I transcription in confluent cells: Rb downregulates rDNA
      transcription during confluence-induced cell cycle arrest.
AB  - When 3T6 cells are confluent, they withdraw from the cell cycle. Concomitant with
      cell cycle arrest a significant reduction in RNA polymerase I transcription (80%
      decrease at 100% confluence) is observed. In the present study, we examined
      mechanism(s) through which transcription of the ribosomal genes is coupled to
      cell cycle arrest induced by cell density. Interestingly with an increase in cell
      density (from 3 - 43% confluence), a significant accumulation in the cellular
      content of hyperphosphorylated Rb was observed. As cell density increased
      further, the hypophosphorylated form of Rb became predominant and accumulated in
      the nucleoli. Co-immunoprecipitation experiments demonstrated there was also a
      significant rise in the amount of hypophosphorylated Rb associated with the rDNA
      transcription factor UBF. This increased interaction between Rb and UBF
      correlated with the reduced rate of rDNA transcription. Furthermore,
      overexpression of recombinant Rb inhibited UBF-dependent activation of
      transcription from a cotransfected rDNA reporter in either confluent or
      exponential cells. The amounts or activities of the rDNA transcription components
      we examined did not significantly change with cell cycle arrest. Although the
      content of PAF53, a polymerase associated factor, was altered marginally
      (decreased 38%), the time course and magnitude of the decrease did not correlate
      with the reduced rate of rDNA transcription. The results presented support a
      model wherein regulation of the binding of UBF to Rb and, perhaps the cellular
      content of PAF53, are components of the mechanism through which cell cycle and
      rDNA transcription are linked. Oncogene (2000) 19, 3487 - 3497

PMID- 10918606
TI  - Growth regulated oncogene-alpha expression by murine squamous cell carcinoma
      promotes tumor growth, metastasis, leukocyte infiltration and angiogenesis by a
      host CXC receptor-2 dependent mechanism.
AB  - Growth Regulated Oncogene-alpha (GRO-alpha) is an autocrine growth factor in
      melanoma and is a member of the C-X-C family of chemokines which promote
      chemotaxis of granulocytes and endothelia through binding to CXC Receptor 2. We
      found previously that variants of murine squamous cell carcinoma PAM 212 which
      grow and metastasize more rapidly in vivo constitutively express increased levels
      of murine GRO-alpha, designated mGRO-alpha, or KC. We have examined the possible
      role of mGRO-alpha expression in malignant progression of squamous cell carcinoma
      PAM 212 in homologous BALB/c and BALB CXC Receptor-2 deficient mice. Transfection
      of the PAM 212 cell line which exhibits low expression of GRO-alpha and malignant
      potential with a pActin-KC vector encoding mGRO-alpha enabled isolation of PAM-KC
      expressing cell lines. These PAM-KC transfectants displayed an increased rate of
      growth and metastasis in BALB/c mice, similar to the highly malignant phenotype
      observed in spontaneously occurring metastatic variants. Furthermore, the PAM-KC
      tumors showed an increase in infiltration of host leukocytes and CD31+ blood
      vessels, consistent with increased CXC chemokine activity. The increased growth
      of PAM-KC cells was attenuated in CXCR-2 deficient mice, indicating that the
      increased growth was dependent in part upon host cells responsive to the CXC
      chemokine. Together, these results show that a CXC chemokine such as GRO-alpha
      can promote malignant growth of murine squamous cell carcinoma by a host CXCR-2
      dependent pathway. Oncogene (2000) 19, 3477 - 3486

PMID- 10918608
TI  - The consequence of p53 overexpression for liver tumor development and the
      response of transformed murine hepatocytes to genotoxic agents.
AB  - To analyse the effect of p53 on liver tumor development, we generated transgenic
      mice overexpressing wild-type p53 in the liver and crossed them with transgenic
      mice in which the expression of the SV40 large T antigen (TAg) induces hepatic
      tumors. Remarkably, whereas preneoplastic TAg liver exhibited anisocaryosis and
      anisocytosis, TAg/p53 liver never presented any dysplastic cells. Moreover,
      whereas expression of p53 did not affect hepatic development, its constitutive
      expression in tumorigenic livers resulted in a significantly enhanced apoptosis
      once nodules had appeared. In contrast, p53 overexpression did not modify the
      elevated proliferation of TAg-transformed hepatocytes and had no effect on
      hepatocarcinoma progression. In vitro analysis of primary hepatocytes exposed to
      various genotoxic agents showed that p53 failed to sensitize normal or TAg
      transformed hepatocytes to apoptosis, except when high doses of doxorubicin, UV-B
      and UV-C radiation were used. Our results confirmed that the hepatocyte cell type
      is very resistant to genotoxic agents and showed that constitutive expression of
      p53 failed to improve their responsiveness. In addition, our results showed that
      suppression of dysplastic cells, probably by restoring normal cytokinesis and
      karyokinesis, and enhancement of apoptosis by means of p53 overexpression were
      insufficient to counteract or delay the TAg-induced liver tumoral progression.
      Oncogene (2000) 19, 3498 - 3507

PMID- 10918609
TI  - Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic
      pathway in glioma cells.
AB  - Ceramide has recently been regarded as a potential mediator of apoptosis. In the
      present study, the effects of Bcl-2 and Bax on the ceramide-mediated apoptotic
      pathways were examined in glioma cells overexpressing Bcl-2 or Bax. Etoposide,
      cisplatin and tumor necrosis factor-alpha induced apoptosis of C6 rat glioma
      cells which was associated with ceramide formation due to activation of neutral
      sphingomyelinase, followed by release of mitochondrial cytochrome c into the
      cytosol and activation of caspases-9 and -3. The growth of C6 cells stably
      overexpressing either Bcl-2 or Bax was almost equal to that of the vector
      transfected cells. Bax overexpression enhanced etoposide-induced apoptosis
      through acceleration of cytochrome c release and caspases activation. However,
      Bax had no effect on ceramide formation. Similar findings were obtained in C6
      cells and U87-MG human glioblastoma cells which were transiently overexpressed
      with Bax. In contrast, Bcl-2 overexpression resulted in a retardation of the
      apoptotic process via prevention of cytochrome c release and caspases activation,
      and ceramide formation was also blocked when Bcl-2 was highly overexpressed in
      glioma cells. In addition, transient overexpression of Bcl-xL also exerted
      inhibitory effects on ceramide formation and apoptotic cell death induced by
      etoposide. These results indicate that Bax promotes apoptosis regardless of
      ceramide formation and that Bcl-2 or Bcl-xL prevents ceramide formation by
      repressing neutral sphingomyelinase as well as ceramide-induced cytochrome c
      release. Oncogene (2000) 19, 3508 - 3520

PMID- 10918611
TI  - SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha
      catalyzed by Ubc3 and Ubc4.
AB  - NF kappa B is an important transcriptional regulator of multiple pro-inflammatory
      genes. In non-stimulated cells NF kappa B is anchored in the cytoplasm via the
      inhibitory protein I kappa B alpha. Following exposure to diverse pro
      inflammatory signals (e.g. TNF alpha, IL1, LPS) various signal transduction
      cascades are initiated converging on the I kappa B kinase (IKK). IKK
      phosphorylates I kappa B alpha on serines 32 and 36 signaling the inhibitory
      protein for ubiquitin-mediated degradation. The SCF beta-TRCP complex is the
      ubiquitin ligase responsible for mediating phosphorylation dependent
      ubiquitination of I kappa B alpha. Here we reconstitute phosphorylation dependent
      ubiquitination of I kappa B alpha using recombinant components. Our results
      suggest that the cullin specificity of the SCF complex may reflect its ability to
      associate with Rbx1. We demonstrate specific ubiquitination of I kappa B alpha by
      Ubc3 and Ubc4 in a phosphorylation and SCF beta-TRCP dependent manner and that
      both are capable of associating with the SCF beta-TRCP complex isolated from
      human cells. Finally, we show that Ubc4 is in excess to Ubc3 in THP.1 cells and
      19 times more efficient in catalyzing the reaction, suggesting that Ubc4 is the
      preferentially used Ubc in this reaction in vivo. Our results also suggest that
      ubiquitin is transferred directly from the Ubc to phospho-I kappa B alpha in a
      SCF beta-TRCP dependent reaction. Oncogene (2000) 19, 3529 - 3536

PMID- 10918610
TI  - Growth inhibition and modulation of kinase pathways of small cell lung cancer
      cell lines by the novel tyrosine kinase inhibitor STI 571.
AB  - Small cell lung cancer (SCLC) is an aggressive cancer characterized by several
      autocrine growth mechanisms including stem cell factor and its receptor c-Kit. In
      order to arrive at potentially new and novel therapy for SCLC, we have
      investigated the effects of the tyrosine kinase inhibitor, STI 571, on SCLC cell
      lines. It has been previously reported that STI 571 does not only inhibit
      cellular Abl tyrosine kinase activity but also the PDGF receptor and c-Kit
      tyrosine kinases at similar concentrations (approximately 0.1 microM). There is
      no expression of the PDGF-receptor, and the Abl kinase is not activated by SCLC,
      but over 70% of SCLC contain the c-Kit receptor. Utilizing this preliminary data,
      we have determined that three (NCI-H69, NCI-H146 and NCI-H209) of five (including
      NCI-H82 and NCI-H249) SCLC cell lines had detectable c-Kit receptors and were
      inhibited in growth and viability at concentrations 1 - 5 microM of STI 571 after
      48 h of treatment. The SCLC cell lines, NCI-H69, NCI-H146 and NCI-H209, showed a
      dose-response (tested between 0.1 - 10 microM) inhibition of tyrosine
      phosphorylation of c-Kit as well as in vitro kinase activity (at 5 microM) of c
      Kit in response to STI 571. STI 571 inhibited cell motility, as assessed by time
      lapsed video microscopy, within 6 h of STI 571 treatment (5 microM). STI 571 also
      decreased intracellular levels of reactive oxygen species (ROS) by at least 60%,
      at a concentration (5 microM) that also inhibited cell growth. Cell cycle
      analysis of STI 571 responsive cells showed that cells were generally slowed in
      G2/M phase, but there was no arrest at G1/S. A downstream phosphorylation target
      of c-Kit, Akt, was not phosphorylated in response to stem cell factor in the
      presence of STI 571. These data imply that STI 571 inhibits growth of SCLC cells
      through a mechanism that involves inactivation of the tyrosine kinase c-Kit. The
      effectiveness of STI 571 in this study suggests this drug may be useful in a
      clinical trial, for patients with SCLC. Oncogene (2000) 19, 3521 - 3528

PMID- 10918612
TI  - Identification and characterization of genes upregulated in cells transformed by
      v-Jun.
AB  - The transcription factor Jun (c-Jun) functions as a recipient of extracellular
      growth signals and converts them into patterns of gene expression. An oncogenic
      variant of c-Jun was isolated from the acutely transforming retrovirus ASV17.
      Overexpression of this viral Jun (v-Jun) induces transformation of chicken embryo
      fibroblasts (CEF) in culture and fibrosarcomas in chickens. v-Jun is a
      constitutively active form of c-Jun and transforms cells presumably by
      deregulating the expression of specific target genes. In this report, we describe
      six genes whose transcripts are upregulated in v-Jun-transformed CEF. Three of
      these genes show homology to known mammalian genes, to MAP kinase phosphatase 2
      (MKP-2), to reversion-induced LIM protein (RIL) and to cytokine-inducible SH2
      containing protein (CIS). Northern blot analysis, using CEF infected with various
      Jun mutants or an estrogen-regulatable Jun chimera, revealed distinct induction
      patterns of individual targets by v-Jun. The chicken RIL homolog showed an
      expression pattern tightly correlated with the activity of v-Jun. Its expression
      is also transformation-dependent, suggesting a role for this gene in v-Jun
      transformation. The newly identified v-Jun targets can serve as molecular markers
      in the v-Jun transformation process. Oncogene (2000) 19, 3537 - 3545

PMID- 10918614
TI  - The role of p53 in death of IL-3-dependent cells in response to cytotoxic drugs.
AB  - This report examines the cytotoxicity of chemotherapeutic agents to primary bone
      marrow-derived IL-3-dependent cells. Such cells derived from p53-null mice were
      resistant to almost 100-fold higher concentrations of the inhibitors of
      deoxyribonucleotide synthesis FUdR, methotrexate and hydroxyurea than cells with
      wild-type p53. In contrast, the cytotoxicity of the DNA damaging agents X
      irradiation, cisplatin or bleomycin was p53-independent. The topoisomerase II
      inhibitor etoposide induced p53-dependent death, which suggests that DNA damage
      may not be its primary mechanism of cytotoxicity in this cell type. An IL-3
      dependent cell line which expresses wild-type p53 was used to demonstrate that
      the ability of cytotoxic drugs to increase p53 expression level does not control
      their ability to induce p53-dependent loss of clonigenicity. Finally, comparison
      with a p53-null IL-3-dependent cell line was used to show that absence of p53
      delays the rate of entry into apoptosis following treatment with either DNA
      damaging agents or inhibitors of deoxyribonucleotide synthesis. This
      distinguishes short-term effects of p53 on rate of entry into apoptosis from its
      role in controlling ultimate cell survival. Oncogene (2000) 19, 3556 - 3559

PMID- 10918613
TI  - Smad-dependent stimulation of type I collagen gene expression in human skin
      fibroblasts by TGF-beta involves functional cooperation with p300/CBP
      transcriptional coactivators.
AB  - Transforming growth factor-beta (TGF-beta) stimulation of Type I collagen gene
      (COL1A2) transcription involves the Smad signal transduction pathway, but the
      mechanisms of Smad-mediated transcriptional activation are not fully understood.
      We now demonstrate that the ubiquitous transcriptional coactivators p300 and CREB
      binding protein (CBP) enhanced basal as well as TGF-beta- or Smad3-induced COL1A2
      promoter activity, and stimulated the expression of endogenous Type I collagen.
      The adenoviral E1A oncoprotein abrogated stimulation of COL1A2 activity in
      transfected fibroblasts, and reduced the basal level of collagen gene expression.
      This effect was due to specific interaction of E1A with cellular p300/CBP because
      (a) a mutant form of E1A defective in p300 binding failed to abrogate
      stimulation, and (b) forced expression of p300/CBP restored the ability of TGF
      beta to stimulate COL1A2 promoter activity in the presence of E1A. The effect of
      p300 on COL1A2 transcription appeared to be due, in part, to its intrinsic
      acetyltransferase activity, as stimulation induced by a histone acetyltransferase
      deficient mutant p300 was substantially reduced. Transactivation of COL1A2 by
      p300 involved the Smad signaling pathway, as Smad4-deficient cells failed to
      respond to p300, and stimulation was rescued by overexpression of Smad4.
      Furthermore, minimal constructs containing only the Smad-binding CAGACA element
      of COL1A2 were transactivated by p300 in the presence of TGF-beta. These results
      indicate, for the first time, that the multifunctional p300/CBP coactivators play
      a major role in Smad-dependent TGF-beta stimulation of collagen gene expression
      in fibroblasts. Oncogene (2000) 19, 3546 - 3555

PMID- 10918615
TI  - Evidence that Argos is an antagonistic ligand of the EGF receptor.
AB  - Argos, the inhibitor of the Drosophila epidermal growth factor (EGF) receptor,
      remains the only known extracellular inhibitor of this family of receptors in any
      organism. The functional domain of Argos includes an atypical EGF domain and it
      is not clear whether it binds to the EGF receptor or if it acts via a distinct
      receptor to reduce Egfr activity indirectly. Here we present two lines of
      evidence that strongly suggest that Argos directly interacts with the EGF
      receptor. First, Argos is unable to inhibit a chimeric receptor that contains an
      extracellular domain from an unrelated RTK, indicating the need for the EGF
      receptor extracellular domain. Second, Argos can inhibit the Drosophila EGF
      receptor even when expressed in human cells, implying that no other Drosophila
      protein is necessary for inhibition. We also report that Argos and the Drosophila
      activating ligand, Spitz, can influence mammalian RTK activation, albeit in a
      cell-type specific manner. This includes the first evidence that Argos can
      inhibit signalling in mammalian cells, raising the possibility of engineering an
      effective human EGF receptor/ErbB antagonist. Oncogene (2000) 19, 3560 - 3562

PMID- 10918616
TI  - Anticipating twin-twin transfusion syndrome in monochorionic twin pregnancy. Is
      there a role for nuchal translucency and ductus venosus blood flow evaluation at
      11-14 weeks?
AB  - Twin-twin transfusion syndrome is a major complication of monochorionic twin
      pregnancies. In foetuses from monochorionic twinning the presence of increased
      nuchal translucency thickness (NT) has been associated with an increased risk of
      developing this syndrome. One of the presumed mechanisms of increased NT is early
      cardiac failure, indirectly indicated by abnormal blood flow in the ductus
      venosus. We present eleven cases of monochorionic twin pregnancies in which
      nuchal translucency thickness and ductus venosus blood flow evaluation was
      performed at 11-14 weeks. In the two cases presenting with nuchal translucency
      discrepancy between the two foetuses along with anomalous ductus venosus blood
      flow in the foetus with increased nuchal translucency, twin-twin transfusion
      syndrome (TTTS) eventually developed. In none of the twins displaying no inter
      twin difference in NT measurements and in those with discrepant NT but normal
      flow in both ductus venosus, was the progression to TTTS observed. In the two
      cases which developed TTTS, foetoscopic laser coagulation of the vascular
      anastomosis was successfully carried out at 18 weeks and normalisation of the
      venous return was registered. These findings suggest that the association of
      increased NT and abnormal flow in the ductus venosus in monochorionic twins may
      be an early manifestation of haemodynamic imbalance between the donor and the
      recipient eventually manifested as twin-twin transfusion syndrome. Further
      studies, however, are necessary to establish the potential role of the
      combination of NT and ductus venosus blood flow assessment as a screening method
      for TTTS.

PMID- 10918617
TI  - Conservative management of triplet pregnancy after delivery of one foetus.
AB  - This paper intends to demonstrate that the conservative management of triplet
      pregnancy after delivery of one foetus is a feasible and reasonable approach.
      Three cases of triplet pregnancy with successful conservative management after
      miscarriage of one foetus, are presented and compared with cases in the
      literature. The route of delivery, as well as the role of tocolysis, cerclage,
      prophylactic antibiotic therapy and corticosteroids are discussed. Guidelines for
      conservative treatment are proposed. The deliveries of our three pregnancies were
      delayed by 63, 44 and 22 days respectively. Foetal and neonatal evolution are
      normal in five of the remaining foetuses. Only one intrauterine death is
      observed. No maternal complications with sequelae are reported. After abortion of
      the first triplet, contractions often persist and the birth of the two remaining
      foetuses may be unavoidable. Nevertheless, in our experience, confirmed by some
      reports in the literature, prolongation of the pregnancy after expulsion of the
      first foetus is possible. It can be achieved by cervical cerclage associated with
      tocolytic and antibiotic therapy. This management is not associated with
      significantly increased foetal-maternal morbidity.

PMID- 10918618
TI  - Complications of triple pregnancy following intracytoplasmic sperm injection: a
      case report.
AB  - A case is presented of pregnancy and delivery of triplets following
      intracytoplasmic sperm injection (ICSI) therapy. Although the outcome was
      satisfactory, with the birth of normal children free from any malformation, most
      of the obstetric and particularly the neonatal complications that can be
      associated with this therapy are illustrated in this case. In addition, from
      point of view of medical costs, concerns are raised about the current policy of
      multiple embryo transfer which is directly responsible for the high rate of
      multiple gestations observed in the IVF/ICSI programme. The authors consequently
      recommend a policy of transferring not more than two embryos per treatment cycle.

PMID- 10918619
TI  - Genetic influences on premature parturition in an Australian twin sample.
AB  - We investigated possible genetic influences on women's liability to preterm
      birth, using data from a large sample of Australian female twin pairs. In a 1988
      90 questionnaire survey, both members of 905 parous twin pairs (579 monozygotic
      and 326 dizygotic) reported on whether deliveries had been more than two weeks
      preterm. Tetrachoric twin pair correlations for first birth were rMZ = 0.20+/
      0.11 and rDZ = -0.03+/-0.14, and for any birth were rMZ = 0.30+/-0.08 and rDZ =
      0.03+/-0.11. Best-fitting models to data contained only additive genetic
      influences and individual environmental effects. Heritability was 17% for preterm
      delivery in first pregnancy, and 27% for preterm delivery in any pregnancy. In
      the former case, however, we could not reject a model without genetic influences.
      Although our data did not allow for differentiation of the varying aetiologies of
      premature parturition, results from this exploratory analysis suggest that
      further investigation of genetic influences on specific reasons for preterm birth
      is warranted.

PMID- 10918620
TI  - Twin-singleton differences in intelligence?
AB  - The twin method has been criticised for its alleged non-generalisability. When
      population parameters of intellectual abilities are estimated from a twin sample,
      critics point to the twin-singleton differences in intrauterine and family
      environments. These differences are suggested to lead to suboptimal cognitive
      development in twins. Although previous studies have reported twin-singleton
      differences in intelligence, these studies had two major drawbacks: they tested
      young twins, and twins were compared with (genetically) unrelated singletons. To
      test accurately whether twin-singleton differences in intelligence exist, a group
      of adult twins and their non-twin siblings were administered the Dutch WAIS-III.
      The group was large enough to detect twin-singleton differences of magnitudes
      reported in earlier investigations. The data were analysed using maximum
      likelihood model fitting. No evidence of differences between adult twins and
      their non-twin siblings on cognitive performance was found. It is concluded that
      twin studies provide reliable estimates of heritabilities of intellectual
      abilities which can be generalised to the singleton population.

PMID- 10918621
TI  - Self-reported reading problems in parents of twins with reading difficulties.
AB  - Parents of 323 twin pairs with reading disability (RD) reported significantly
      more problems learning to read (16% of mothers and 33% of fathers) than parents
      of 309 twin pairs without reading difficulties (6% of mothers and 9% of fathers).
      These rates of self-reported reading problems in parents of twins are highly
      similar to those previously obtained in parents of non-twin children with RD and
      controls, suggesting that the etiology of reading deficits in twin and non-twin
      children may also be highly similar. Moreover, within both the RD and control
      samples, twins whose parents self-reported a positive history of reading problems
      had lower reading performance test scores, on average, than those whose parents
      reported no reading problems. Therefore, results of the present twin study
      support those of previous studies with non-twin children in which parental self
      reports have been found to provide a valid index of family history status for
      reading difficulties.

PMID- 10918622
TI  - On the application of queuing theory for analysis of twin data.
AB  - A mathematical model based on queuing theory is used to study the dynamics of
      environmental influence on twin pairs. The model takes into consideration genetic
      factors and effects of nonshared environment. Histograms are exploited as base
      analysed characteristics, with the method of minimum chi-square yielding
      estimated characteristics. The proposed technique was applied to analysis of
      longitudinal data for MZ and DZ twins. It was shown that the same environment
      impact may yield different contributions to final variances of the IQ parameters
      under investigation. Magnitudes of these contributions depend on the genetic
      factor represented by distributions of an analysed parameter at the point of
      birth.

PMID- 10918624
TI  - Improving the treatment of infertility: towards avoiding high order multiple
      gestation.

PMID- 10918623
TI  - Predictive power of individual genetic and environmental factor scores.
AB  - This study explores the use of an individual's genetic (IGFS) and environmental
      factor score (IEFS), constructed using genetic model fitting of a multivariate
      strength phenotype. Maximal isometric and dynamic strength measures, one maximal
      repetition load (1RM) and muscle cross-sectional area (MCSA) were measured in 25
      monozygotic and 16 dizygotic twin pairs. The use of IGFS and IEFS in predicting
      the sensitivity to environmental stress was evaluated by the association of the
      scores with strength training gains after a 10-week high resistance strength
      training programme. Results show a high contribution of genetic factors to the
      covariation between maximal strength and muscle cross-sectional area (84-97%) at
      pre-training evaluation. Individual factor scores explained the largest part of
      the variation in IRM and other strength measures at pre-training and post
      training evaluation respectively. Genes that are switched on due to training
      stress (gene-environment interaction) could explain the decrease in explained
      variation over time. A negative correlation was found between IGFS and strength
      training gains (-0.24 to -0.51, P < 0.05); individuals with a high IGFS tend to
      gain less strength than individuals with low IGFS. Individual environmental
      factor scores have lower differential power. The predictive value of the IGFS has
      potential utility in identifying an individual's susceptibility to environmental
      stress in a variety of multifactorial characteristics, eg diseases and
      impairments, and for selection of sib pairs for QTL analyses.

PMID- 10918625
TI  - Maternal metabolic abnormalities in twin-to-twin transfusion syndrome at mid
      pregnancy.
AB  - We report abnormal maternal laboratory parameters in twin-to-twin transfusion
      syndrome (TTTS) at mid-pregnancy. A retrospective chart review was undertaken of
      109 patients with TTTS evaluated for placental laser surgery. Complete blood
      count (CBC), blood type and Rh factor, urine analysis and serum chemistry panel
      were obtained preoperatively, with the CBC and serum albumin repeated on the
      first postoperative day. The mean gestational age was 21.2+/-1.7 weeks. Initial
      abnormal values included hematocrit (32.1+/-3.0%), hemoglobin (11.0+/-1.03 g/dl),
      serum magnesium (1.71+/-0.17 mg/dl), total protein (6.08+/-0.55 g/dl) and albumin
      (3.06+/-0.34 g/dl). Despite minimal blood loss and conservative fluid replacement
      mean hematocrit, hemoglobin, and albumin were 27.3+/-2.74%, 9.3+/-0.94 g/dl and
      2.56+/-0.23 g/dl, respectively on postoperative day one. Weight gain (8.0+/-5.5
      lb.) and low urinary output were characteristic peri-operative events. Maternal
      hypoproteinemia and anemia occur in TTTS at mid-pregnancy. This may contribute
      independently to amniotic fluid production rates in the fetuses, and explain in
      part the maternal sensitivity to intravenous fluids in multiple pregnancy.

PMID- 10918626
TI  - The unexpected reflectiveness of cortical synapses.

PMID- 10918627
TI  - Pain control: breaking the circuit.

PMID- 10918628
TI  - Reply

PMID- 10918629
TI  - Does cyclosporin A generate free radicals?

PMID- 10918630
TI  - Pass the protease: new interactions between GPCRs.

PMID- 10918631
TI  - PDE4D-deficient mice knock the breath out of asthma.

PMID- 10918632
TI  - Retinoids offer hope for the treatment of emphysema.

PMID- 10918633
TI  - How hot is chilli?

PMID- 10918634
TI  - Is histamine the final neurotransmitter in the entrainment of circadian rhythms
      in mammals?
AB  - Adaptation of circadian rhythms to the environmental light-dark cycle is
      necessary for the survival of organisms. This synchronization or entrainment is
      only caused by light (photic input) during the dark period, according to the
      internal biological clock of an organism. During the light period, internal
      factors (non-photic input), rather than light, are able to entrain circadian
      rhythms. In this article, the data that implicate the neurotransmitter system for
      histamine in circadian entrainment are reviewed. Furthermore, we speculate that
      histamine receptors are the final gate at which both photic and non-photic
      entrainment mechanisms converge before sending a resetting signal to the
      intracellular biological clock.

PMID- 10918635
TI  - More mysteries of opium reveal'd: 300 years of opiates.
AB  - This year is the 300th anniversary of the publication of one of the first books
      written about opiates and their subjective effects. Since that time the influence
      of opiates in Western society has grown enormously, as has our knowledge of the
      mechanisms by which these drugs produce their effects. Wars have been fought over
      the use of opiates and the economies of several countries depend on their
      production. In this article, some aspects of the history and effects of opiates
      on the arts in particular are explored.

PMID- 10918636
TI  - Localization of G-protein-coupled receptors in health and disease.
AB  - G-protein-coupled receptors (GPCRs) represent a superfamily of proteins,
      characterized by seven transmembrane alpha-helices, that signal through
      interactions with a family of heterotrimeric GTP-binding proteins, referred to as
      G proteins. The broad range of physiological functions associated with GPCRs
      indicates that a better understanding of these receptors and their regulation can
      provide a solid foundation for novel pharmacological interventions in a variety
      of disease states.

PMID- 10918637
TI  - Leptin as a regulator of adipose mass and reproduction.
AB  - Leptin, an adipocyte-derived hormone, informs neuroendocrine pathways about the
      status of energy stores in adipose tissue. The integration of this peripheral
      signal in hypothalamic networks results in activation of peripheral metabolic
      pathways that control energy build-up and expenditure. Firing of the reproductive
      cascade of hormones at puberty and its regulation in adults is tightly associated
      with energy metabolism and is thus regulated by leptin. This article provides an
      update of past and present theories that link nutrition and reproduction in light
      of new research.

PMID- 10918638
TI  - Pharmacological magnetic resonance imaging: a new application for functional MRI.
AB  - Various methods, including functional magnetic resonance imaging (fMRI), have
      recently been developed to allow investigators to study functional activity in
      the living brain. Such techniques are now being used to investigate regionally
      specific brain activity associated with the administration of CNS-active drugs.
      fMRI in particular is increasingly recognized as being a relatively non-invasive
      way to perform pharmacological investigations in experimental animals, healthy
      human volunteers, and individuals with CNS disease. This use of fMRI, dubbed
      'pharmacological MRI' or 'phMRI', holds the promise of providing relatively
      straightforward pharmacodynamic assays and can be used to establish brain
      penetrability parameters, or dose-ranging information for novel therapeutic
      compounds.

PMID- 10918639
TI  - Epidemiology and risk factors for heart failure in the elderly.
AB  - Heart failure is a common problem in the elderly population, affecting 10% or
      more of persons more than 80 years of age. Heart failure is most likely to
      develop in the elderly population, with an annual incidence of 20 to 30 cases per
      1000 persons aged more than 80 years. Heart failure is not only common in the
      elderly population but also commonly fatal, with fewer than 30% of elderly
      persons surviving 6 years after their first hospitalization for heart failure.
      Common risk factors leading to heart failure include coronary heart disease,
      systolic hypertension, and diabetes mellitus. The global aging of the population
      will perpetuate the epidemic of heart failure into the next century.

PMID- 10918640
TI  - Cardiovascular aging in health.
AB  - Major focuses of geriatric medicine are cardiovascular diseases with increases in
      prevalence in older people and how aging might modify the risk factors, clinical
      manifestations, treatment strategies, and prognoses of these diseases.
      Quantitative information on age-associated alterations in cardiovascular
      structure and function in health is essential to define and target the specific
      characteristics of the cardiovascular aging process that render it the major risk
      factor for cardiovascular diseases. Such information also is required to
      differentiate among the limitations of elderly individuals that relate to disease
      and limitations that may fall within expected normal limits. Differences in
      cardiovascular function between older and younger individuals have been described
      extensively in the literature, but confusion often arises in the interpretation
      of these differences because of a failure to acknowledge or to control for
      interactions among age, disease, and lifestyle. The Baltimore Longitudinal Study
      on Aging has made an effort to characterize the effects of aging on multiple
      aspects of cardiovascular structure and function. The concepts that have evolved
      from this and other studies are discussed.

PMID- 10918641
TI  - Clinical manifestations, diagnostic assessment, and etiology of heart failure in
      elderly patients.
AB  - Heart failure in elderly patients may be difficult to diagnose because of a lack
      of typical symptoms and physical findings that are common in younger patients
      with this disorder. When present, the symptoms and signs are often nonspecific
      and mistakenly may be thought to be caused by other disorders that are commonly
      present in elderly patients. In older elderly patients, the symptoms and signs
      may be obscured by the presence of aging changes or other diseases. As a result
      of these problems, physicians must be highly suspicious of heart failure in all
      elderly patients who have underlying heart disease or who present with
      nonspecific symptoms that may represent heart failure. After the diagnosis of
      heart failure is established, the cause must be determined and systolic and
      diastolic ventricular dysfunction must be differentiated.

PMID- 10918642
TI  - Role of echocardiography in the diagnosis and management of heart failure in the
      elderly.
AB  - Heart failure is the most common cause of cardiovascular hospitalization in older
      adults in the United States. This disease is common, disabling, and commonly
      fatal, especially in the elderly population. Hypertension and coronary artery
      disease are the leading causes of heart failure. A precise diagnosis of the
      cardiac abnormality is paramount for adequate treatment, and echocardiography
      offers the most comprehensive, noninvasive evaluation. With an organized approach
      using two-dimensional and Doppler echocardiography, the systolic and diastolic
      left ventricular performance can be determined; the cardiac output, pulmonary
      artery, and ventricular filling pressures can be estimated; and surgically
      correctable valve disease can be identified. The response and success of
      treatment also may be monitored by the judicious use of echocardiography.

PMID- 10918643
TI  - Nonpharmacologic treatment of heart failure in the elderly.
AB  - Nonpharmacologic therapy is an integral part of the management of elderly
      patients with heart failure. Reinforcement of dietary sodium restriction and
      other nutritional concerns are critical features of therapy. Quality standards
      for the management of patients with heart failure are being developed, and the
      implementation of these standards is a goal of clinicians. A multidisciplinary
      approach to elderly patients with heart failure is beneficial.

PMID- 10918644
TI  - Heart failure with normal systolic function.
AB  - Contrary to popular belief, population studies indicate that most elderly
      patients with heart failure have preserved left ventricular systolic function
      (i.e., presumed diastolic heart failure). Several normal aging changes may
      predispose older individuals to diastolic heart failure, including increased
      hypertrophy and stiffness of the left ventricle, increased vascular stiffness,
      and decreased cardiovascular reserve. Progress in diastolic heart failure has
      been hindered by a lack of standard case definition; absence of a readily
      available, reliable test to quantitate diastolic function; poor understanding of
      the pathophysiology of heart failure; and lack of data from randomized,
      controlled, multicenter trials. Typical patients are older women with chronic
      hypertension, left ventricular hypertrophy, chronic exercise intolerance, and
      occasional acute exacerbations (pulmonary edema). Although heart failure is a
      clinical, bedside diagnosis, echocardiography is helpful in differentiating
      diastolic from systolic heart failure and in ruling out other disorders. Although
      optimal pharmacologic therapy has not been clarified, control of blood pressure;
      exercise conditioning; and a multidisciplinary, case management approach seem
      beneficial.

PMID- 10918645
TI  - Drug therapy of heart failure caused by systolic dysfunction in the elderly.
AB  - The presence of multiple medical illnesses often distinguishes elderly patients
      with heart failure and can make pharmacologic management of symptomatic heart
      failure challenging in this population. Physiologic changes that occur with
      normal aging may complicate clinical assessment. Limited data from large clinical
      trials of heart failure therapy are applicable to aged patients. Available data
      suggest that elderly patients should be treated with the same regimen as younger
      patients but that more careful attention should be paid to dosing, especially
      when initiating a new drug. History and physical examination techniques can be
      used to uncover evidence of congestion and inadequate perfusion and are critical
      adjuncts when making therapeutic decisions. The objectives of therapy for elderly
      patients with heart failure must be individualized within the larger context of
      patients' goals and stage of life.

PMID- 10918646
TI  - Heart failure complicating acute myocardial infarction.
AB  - Older people with congestive heart failure associated with acute myocardial
      infarction should be treated with loop diuretic therapy. Class I indications for
      the use of early intravenous beta blockade in patients with acute myocardial
      infarction are patients without a contraindication to beta blockers who can be
      treated within 12 hours of onset of myocardial infarction; patients with
      continuing or recurrent ischemic pain; and patients with tachyarrythmias, such as
      atrial fibrillation with a rapid ventricular rate. Class I indications for the
      use of angiotensin-converting enzyme inhibitors during acute myocardial
      infarction are (1) patients within the first 24 hours of onset of a suspected
      acute myocardial infarction with ST segment elevation in two or more anterior
      precordial leads or with clinical heart failure in the absence of significant
      hypotension or contraindications to the use of angiotensin-converting enzyme
      inhibitors, (2) patients with myocardial infarction and a left ventricular
      ejection fraction of less then 40%, (3) and patients with clinical heart failure
      on the basis of systolic pump dysfunction during and after convalescence from
      acute myocardial infarction. No class I indications exist for using calcium
      channel blockers or magnesium during acute myocardial infarction.

PMID- 10918647
TI  - Interventional therapy in heart failure management.
AB  - The incidence and prevalence of congestive heart failure are rapidly increasing
      because of the progressive decrease in age-adjusted mortality rates for coronary
      artery disease and hypertensive heart disease, together with the progressive
      aging of the US population. Despite great advances in maximal medical therapy,
      most patients with symptomatic congestive heart failure can expect functional
      impairment, interludes of worsening symptomatology, and a shortened life span.
      Thus, it is appropriate to ask whether the interventional revolution that is
      under way for the management of ischemic cardiovascular disease can be applied
      with benefit to the management of congestive heart failure. The use of
      interventional therapies for the treatment of elderly patients with congestive
      heart failure caused by coronary artery disease, valvular heart disease, or renal
      vascular disease is addressed.

PMID- 10918648
TI  - Surgical management of heart failure.
AB  - Surgical therapy for congestive heart failure can offer gratifying results in
      selected elderly patients. Several trials have shown a survival advantage for
      surgical revascularization compared with medical therapy in the treatment of
      ischemic cardiomyopathy. Aortic valve replacement is highly effective in treating
      elderly patients with heart failure caused by severe aortic stenosis, and
      stentless aortic valves seem to provide a survival advantage in elderly patients
      with low-gradient aortic stenosis. Mitral valve repair with or without coronary
      revascularization has been used successfully in patients with severe mitral
      regurgitation. Transplantation is a viable but rarely used option for elderly
      patients with congestive heart failure. Totally implantable ventricular assist
      devices are an exciting new option for elderly patients with congestive heart
      failure who are not heart transplantation candidates.

PMID- 10918649
TI  - Management of arrythmias.
AB  - The management of arrhythmias in elderly patients with congestive heart failure,
      including atrial fibrillation, ventricular tachyarrhythmias, and
      bradyarrhythmias, is described. Patients with atrial fibrillation can be treated
      with rate control anticoagulation for stroke prevention or by attempt at
      cardioversion and maintenance of sinus rhythm. Elderly patients remaining in
      atrial fibrillation benefit from anticoagulation provided that no
      contraindication exists. In patients surviving malignant ventricular arrhythmias,
      defibrillator implantation is beneficial in elderly patients with heart failure.
      Prognosis and treatment of nonsustained arrhythmias depends on the presence of
      underlying cardiac abnormalities. In the healthy elderly population, treatment is
      not indicated. In patients with coronary artery disease, decreased ejection
      fraction, and nonsustained ventricular tachycardia, electrophysiology can further
      stratify risk, and defibrillator implantation can improve survival if arrhythmias
      are induced. This benefit is as great in elderly patients as in younger patients.
      Symptomatic bradycardias are increasingly common with advancing age. Symptoms are
      improved with pacing, with maximum benefit from physiologic rather than
      ventricular pacing. Although the elderly population poses a unique challenge when
      faced with arrhythmias, an active approach not only saves lives but also reduces
      morbidity.

PMID- 10918650
TI  - Cardiac rehabilitation and secondary prevention programs for elderly cardiac
      patients.
AB  - The utility of cardiac rehabilitation for elderly cardiac patients is
      controversial, and cost, logistic barriers, and encumbering comorbidities often
      seem disproportionate. Many clinicians view the emphasis of cardiac
      rehabilitation on behavior modification and risk-factor reduction as irrelevant
      for very old adults and consider pure exercise programs as appropriate
      alternatives. The strong rationale for cardiac rehabilitation and secondary
      prevention is elucidated, and available corroborating data are presented. The
      benefits of exercise prescription in cardiac rehabilitation and synchronized risk
      factor reduction are pertinent to aging and age-related heart disease, including
      coronary heart disease and heart failure.

PMID- 10918651
TI  - Comorbidity in heart failure in the elderly.
AB  - Heart failure occurs principally in the geriatric population and often is
      associated with severe comorbidity. Comorbid conditions that occur in the
      geriatric population at a prevalence equal to or greater than that of heart
      failure itself include the brain failure syndromes (i.e., delirium and dementia),
      depression, falls, postural hypotension, urinary incontinence, undernutrition,
      frailty, sensory deprivation, polypharmacy, and lack of social support. The
      effect of major geriatric comorbidities on the management of patients with heart
      failure is reviewed.

PMID- 10918652
TI  - Psychosocial considerations in elderly patients with heart failure.
AB  - Neuropsychiatric conditions, such as Alzheimer's dementia, and complications,
      such as delirium, are common in elderly patients with heart failure. Persistent
      alcohol abuse and cigarette smoking sometimes contribute to the onset and
      progression of heart failure. Major depression and other depressive disorders are
      common in this population and have adverse effects on functional status, quality
      of life, and prognosis. Anxiety and social isolation are clinically significant
      problems in many cases. These problems often are treatable and deserve more
      clinical attention than they typically receive.

PMID- 10918653
TI  - End-of-life care for elderly patients with heart failure.
AB  - The mortality rate of elderly persons with heart failure is high despite the
      introduction of several effective therapeutic interventions during the past
      decade. The management of end of life, often associated with distressing symptoms
      and multiple hospitalizations, is a significant clinical problem. Skillful and
      effective management requires expert knowledge of the heart failure syndrome, but
      the critical dimension of care relates to detailed knowledge about a patient's
      comorbidities, extent of debility, values, and desires. Discussing end-of-life
      issues early in the course of illness is essential for determining the
      appropriate levels of intensity of care and for defining the circumstances in
      which patients wish to be hospitalized and when hospital care offers little
      potential for increased comfort or longevity. Early and repeated discussions are
      needed to consider matters such as living wills, do-not-resuscitate orders, and
      power of attorney. In light of the complexity of the health care system,
      including involvement of multiple caregivers, end-of-life issues are among the
      most demanding of a physician's time, but when end-of-life care is managed
      effectively, health care providers often are rewarded with the gratitude of
      patients and their families for minimizing suffering and providing optimal
      opportunities for patients to participate in the affairs of family and the
      community.

PMID- 10918654
TI  - Cellular physiology of the vocal folds.
AB  - This article discusses cellular architecture and physiology relevant to phonation
      biology. The mucociliary blanket and its role in external vocal fold lubrication
      are presented. The epithelium, basement membrane zone, and lamina propria all
      have specific roles in oscillating tissue. Three cell types, fibroblast,
      myofibroblast, and macrophage, maintain important and unique roles. Protein
      turnover in the lamina propria is important, and slowing matrix turnover may be a
      leading factor in creating some of the characteristics associated with vocal
      senescence. Lastly, aspects of cellular health and cellular pathology are
      discussed.

PMID- 10918656
TI  - Medical and vocal history in the evaluation of dysphonia.
AB  - Dysphonia is one of the more common complaints resulting in referral to the
      otolaryngologist-head and neck surgeon. The accurate diagnosis and management of
      dysphonia is based on a complete medical and vocal history. This article presents
      an approach to elicit pertinent information from the patient presenting with
      dysphonia. The evaluation is divided into the history of present illness, past
      medical history, past surgical history, review of systems, medications, and a
      social history.

PMID- 10918657
TI  - Perceptual and laboratory assessment of dysphonia.
AB  - The voice laboratory is an essential tool in the voice clinic. It provides a
      functional diagnosis of disturbed voice production, demonstrating the deviant
      characteristics, limitations, and possibilities for change. As voice is
      multidimensional, several aspects need to be documented, quantified, and
      analyzed: perception, stroboscopy, aerodynamics, acoustics, self-evaluation by
      the patient, and in specific cases, physiologic signals, such as
      electroglottography, flow glottography, nasometry, and electromyography.
      Effectiveness and outcome studies rely on such data.

PMID- 10918655
TI  - Vocal fold physiology.
AB  - This article examines the physiologic factors responsible for the production of
      phonation in humans. The article begins with an explanation of the control
      mechanisms of phonation and theories of vocal fold vibration. The physiologic
      concepts are based on the myoelastic-aerodynamic, body-cover, and mucosal wave
      theories. An evaluation of the cover-body theory is explained in terms of pitch
      control. The factors that regulate the vocal folds to produce pitch changes,
      intensity variation, and register effects are outlined. The changes in pitch,
      intensity, and voice qualities are related to the vocal fold mass, tension,
      subglottic pressure, and airflow generated by the phonatory systems. A brief
      summary of abnormal voice production is given in terms of disordered physiology
      and the emerging theory of chaos.

PMID- 10918658
TI  - Diagnostic laryngeal endoscopy.
AB  - Diagnostic laryngeal endoscopy is a crucial part of the evaluation of patients
      with dysphonia. Multiple methods are available, and often several are required to
      provide a comprehensive physiologic and anatomic evaluation. The pros and cons of
      each method are discussed and the development of a standardized examination
      protocol is reviewed.

PMID- 10918659
TI  - Laryngeal electromyography: diagnostic and prognostic applications.
AB  - Laryngeal electromyography is a crucial diagnostic test in laryngology. Laryngeal
      electromyography is important for the diagnosis of vocal fold paresis and
      cricoarytenoid joint pathology (e.g., arytenoid dislocation). In addition,
      laryngeal electromyography offers prognostic information regarding potential
      vocal fold paralysis recovery, which can improve the management strategies for
      vocal fold paralysis.

PMID- 10918660
TI  - Dysphonia related to medical therapy.
AB  - It is essential for laryngologists, speech and language pathologists, and others
      caring for professional voice users to be familiar with the potential vocal
      effects of any substance ingested by a professional voice patient. This article
      reviews pharmacologic agents that may have laryngeal side effects. Essentially,
      any ingested substance is suspect as a cause for voice dysfunction. It is also
      necessary for laryngologists to educate voice professionals about the
      consequences of drugs on the voice and the potential problems associated with
      properly prescribed medication.

PMID- 10918661
TI  - Laryngopharyngeal reflux: state of the art diagnosis and treatment.
AB  - Gastroesophageal reflux has been implicated in the pathogenesis of a wide variety
      of otolaryngologic disorders. Patients with otolaryngologic disorders associated
      with gastroesophageal reflux infrequently have the classic symptoms of
      gastroesophageal reflux, such as heartburn. Clinical presentation of
      laryngopharyngeal reflux is commonly characterized by chronic intermittent
      symptoms. A meticulous synthesis of the information obtained from a complete
      otolaryngologic examination, diagnostic tests, and response to treatment is
      essential for the efficient management of patients with otolaryngologic disorders
      associated with laryngopharyngeal reflux.

PMID- 10918662
TI  - The evolution of the assessment and treatment of paralytic dysphonia.
AB  - Vocal fold paralysis has been an omnipresent disorder throughout the annals of
      laryngologic history since the origin of the specialty in 1858. The attendant
      complexity of laryngoscopic presentation, physiologic dysfunction, and surgical
      rehabilitation have led to a rich heritage of scientific investigations that can
      be traced through the past 140 years. The following historical summary provides
      the reader with a working knowledge of past experiences that connect to current
      initiatives and portend future progress.

PMID- 10918663
TI  - Arytenoid adduction and medialization laryngoplasty.
AB  - Arytenoid adduction and medialization laryngoplasty have become the mainstay of
      static surgical rehabilitation of the larynx after vocal fold paralysis. The
      rationale for considering one versus a combination of the two procedures has not
      been well addressed. This article outlines the basic science of the procedures
      and the clinical technical modifications necessary to make the surgery easier.

PMID- 10918664
TI  - New procedures for paralytic dysphonia: adduction arytenopexy, Goretex
      medialization laryngoplasty, and cricothyroid subluxation.
AB  - Laryngoplastic phonosurgery has evolved to be a dominant treatment modality for
      paralytic dysphonia. The postoperative vocal outcome from the combined use of
      adduction arytenopexy, Goretex medialization laryngoplasty, and cricothyroid
      subluxation is such that most patients will have a normal phonation time and more
      than two octaves of dynamic range with minimal acoustic perturbation. With the
      addition of the adduction arytenopexy and cricothyroid subluxation procedures to
      the armamentarium of the phonosurgeon, all parameters for static reconstruction
      of the paralyzed vocal fold have been addressed.

PMID- 10918665
TI  - Posterior glottic stenosis and bilateral vocal fold immobility: diagnosis and
      treatment.
AB  - Posterior glottic stenosis and bilateral vocal fold immobility cause obstruction
      of the airway at the glottis. Presentation of this problem may vary according to
      the cause. Full evaluation of the status of the larynx is crucial with regard to
      the mobility of the arytenoid cartilage and innervation of the laryngeal
      musculature. There are many techniques for surgically treating this condition,
      each with advantages and disadvantages. The surgeon should be familiar with a
      variety of these procedures and be able to adapt to each patient's situation.

PMID- 10918666
TI  - Botulinum toxin for the treatment of spasmodic dysphonia.
AB  - Spasmodic dysphonia is a focal laryngeal dystonia. Laryngeal dystonia presents
      as: adductor spasmodic dysphonia with the characteristic strain-strangle voice;
      abductor spasmodic dysphonia with hypophonia and breathy breaks in connected
      speech; and adductor respiratory dystonia with paradoxical vocal fold motion and
      intermittent stridor. Current treatment with periodic laryngeal intramuscular
      injections of botulinum toxin A has allowed patients to function more normally.
      In this article, the authors' treatment paradigm and experience in treating over
      900 patients with laryngeal dystonia are discussed.

PMID- 10918667
TI  - Neurolaryngology: past, present, and future.
AB  - Neurolaryngology is the study and management of disorders that impair neural
      control of the larynx and pharynx in breathing, swallowing, and speech. Advances
      in functional endoscopy and fluoroscopy and increased understanding of
      neurophysiology have greatly facilitated the development of this discipline. The
      empiric observations of effective therapies have been equally important, however.
      In comparison to other fields of medicine, neurolaryngology is a relatively young
      discipline, and much remains to be discovered and developed.

PMID- 10918668
TI  - Outcome measurements and quality of life in voice disorders.
AB  - Although outcome research in the area of voice is truly in its beginning stages,
      the clinician who treats voice disorders should be aware of its potential
      usefulness. It is possible to identify a patient's perception of severity using
      one of several voice-specific outcome measures. Using these measures may also
      direct treatment in a more specific manner. For example, although a patient may
      have a vocal fold polyp or cyst, a low Voice Handicap Index may indicate that
      immediate surgery is unnecessary. A more conservative treatment approach or
      observation only may be appropriate. In this way, medical resources and time can
      be used most appropriately. Certainly one must never compromise treatment when
      significant disease is suspected. In the absence of significant disease, however,
      the patient's perceived severity and need to recover vocal function may determine
      treatment.

PMID- 10918669
TI  - Prevention of coronary artery disease.
AB  - The magnitude of cardiovascular disease is enormous. When the risk factors that
      predispose a patient to heart disease are recognized early and the appropriate
      intervention is instituted, the incidence of morbidity and mortality from
      coronary heart disease can be reduced. Lifestyle modification and the judicious
      use of medications can improve the complications of heart disease and prevent its
      onset.

PMID- 10918670
TI  - Hyperlipidemia.
AB  - Coronary heart disease (CHD) is prevalent and often related to an unhealthy diet
      and hyperlipidemia. The diagnosis of hyperlipidemia should be carefully made,
      using more than one measurement in the manner described. An assessment of risks
      allows one to decide whom to treat. Patients with CHD should be treated
      aggressively but it is less clear how aggressive to be with patients without CHD.
      Diet and exercise recommendations are appropriate for almost all patients. For
      those for whom the benefit is greater than the potential risks, statins are first
      line drug therapy and they appear to have beneficial effects aside from their
      lipid-lowering properties.

PMID- 10918671
TI  - Hypertension.
AB  - The current JNC-VI criteria for diagnosis and classification of hypertension are
      discussed. The laboratory evaluation of both essential and secondary hypertension
      is examined, and recommendations are made in this regard. Finally, the
      complications and treatment of essential hypertension and the causes and
      management of resistant hypertension are discussed.

PMID- 10918672
TI  - Atherosclerotic vascular disease: management of angina in the office setting.
AB  - A discussion of primary care issues related to the management of angina in the
      office setting is warranted because of recent developments. These developments
      include new pharmacotherapies, recent insights into the pathophysiology of
      angina, and increased recognition of the role of the diseased endothelium in
      sequelae of coronary artery disease.

PMID- 10918673
TI  - The acute myocardial infarction.
AB  - Cardiovascular death is the number one cause of death in the United States, with
      a rate that is more than double that for cancer. Over half of these
      cardiovascular deaths are due to acute myocardial infarction. Management of the
      patient with acute myocardial infarction during and after hospitalization is
      discussed with an emphasis on primary and secondary prevention, patient autonomy
      and decision making. There is also a review of the directions that treatment of
      acute myocardial infarction will take in the future.

PMID- 10918674
TI  - Management of heart failure.
AB  - Heart failure imposes a major burden on society. Primary care physicians, who
      care for 70% of all heart-failure patients, have opportunities to reduce the
      economic and mortality impact of this disease by improved outpatient management.
      Management tasks for these patients are discussed. Successful completion of these
      tasks will lead to an improvement in functional capacity, fewer hospitalizations,
      and longer lives for heart-failure patients.

PMID- 10918675
TI  - Atrial arrhythmias.
AB  - Atrial arrhythmias are commonly encountered by the primary care clinician. They
      are usually asymptomatic or have only minor symptoms, unless the ventricular rate
      becomes very rapid. The challenges for the clinician are to recognize the benign
      from the more severe arrhythmias, to identify and treat the precipitating cause,
      to control the symptoms that concern the patient, and to prevent any
      complications. There are new medicinal and nonmedicinal treatments available that
      offer greater likelihood of acute and long-term success in the treatment, and
      sometimes cure, of the original arrhythmias.

PMID- 10918676
TI  - Ventricular arrhythmias.
AB  - Sudden cardiac death remains a leading cause of death in the United States. It is
      usually due to ventricular arrhythmia, either ventricular tachycardia or
      ventricular fibrillation. The probability of life threatening ventricular
      arrhythmia correlates closely with underlying structural heart disease. In any
      patient presenting with a ventricular arrhythmia, a careful search for underlying
      causes is required, and treatment should be considered primarily if it will
      prolong survival. Treatment of patients without underlying heart disease who are
      experiencing ventricular ectopy, and/or nonsustained ventricular tachycardia,
      consists of reassurance and education. If symptoms are severe, a beta-blocker is
      an appropriate choice for drug treatment. Patients with ventricular arrhythmia
      and structural heart disease are generally best managed in conjunction with a
      cardiologist.

PMID- 10918677
TI  - Valvular heart disease.
AB  - Given the high prevalence of valvular heart disease, primary care physicians need
      to be familiar with the most common valvular heart diseases and their clinical
      manifestations. Knowledge of the natural history of the most common valvular
      heart diseases is important because the onset of symptoms often is the point at
      which intervention becomes necessary. Most valvular heart diseases are amenable
      to surgical intervention, which can afford a symptom-free and relatively normal
      life span. Therefore, primary care physicians must be familiar with the
      indications for therapeutic interventions and the most appropriate interventions
      currently recommended.

PMID- 10918678
TI  - Heart disease in women.
AB  - Women face a disparity in the evaluation and treatment of coronary artery
      disease, even though coronary artery disease is the leading cause of death for
      women in the United States. Primary care physicians play an important role in the
      identification and treatment of risk factors and comorbidities. It is their
      obligation to ensure that women receive equal and appropriate care, and to
      advocate for their patients.

PMID- 10918679
TI  - Heart disease in children.
AB  - Advances in the understanding of the pathophysiology, diagnosis, and medical and
      surgical management of neonates with cardiovascular disease has led to their
      improved survival rates. These improvements have resulted in an increased number
      of pediatric patients presenting to the primary care physician's office with
      underlying heart disease. Understanding the genetic, congenital, or acquired
      etiologies to the various pediatric heart diseases is crucial to preventing these
      lesions and treating these patients.

PMID- 10918680
TI  - Diagnostic testing.
AB  - The results of cardiac tests must always be interpreted through the lens of
      pretest probabilities created by the history and the physical examination. Tests
      should be chosen with a clear diagnostic and prognostic purpose in mind. A clear
      understanding of the relationship between the history and physical examination
      and more technologic diagnostic testing improves the primary care physician's
      ability to evaluate potential cardiac disease in an efficient and cost-effective
      manner.

PMID- 10918681
TI  - A piece of my mind: the cardboard box.

PMID- 10918683
TI  - Photo/essay: the not-so-silent marks of torture.

PMID- 10918684
TI  - Health care of torture survivors.

PMID- 10918685
TI  - Is domestic violence screening helpful?

PMID- 10918686
TI  - Best tactic for clinician safety: be prepared.

PMID- 10918688
TI  - Domestic violence: what to ask, what to do.

PMID- 10918689
TI  - Apocalypse now: HIV/AIDS in Africa exceeds the experts' worst predictions.

PMID- 10918690
TI  - Biological warfare in the 1940s and 1950s.

PMID- 10918691
TI  - Biological warfare in the 1940s and 1950s.

PMID- 10918693
TI  - Placebo effect in posttraumatic stress disorders.

PMID- 10918695
TI  - Reporting drug abuse in the emergency department.

PMID- 10918697
TI  - Are magnets effective for pain control?

PMID- 10918698
TI  - Are magnets effective for pain control?

PMID- 10918699
TI  - Are magnets effective for pain control?

PMID- 10918700
TI  - Are magnets effective for pain control?

PMID- 10918701
TI  - Relationship between illegal use of handguns and handgun sales volume.

PMID- 10918702
TI  - Mental health, social functioning, and attitudes of Kosovar Albanians following
      the war in Kosovo.
AB  - CONTEXT: The 1998-1999 war in Kosovo had a direct impact on large numbers of
      civilians. The mental health consequences of the conflict are not known.
      OBJECTIVES: To establish the prevalence of psychiatric morbidity associated with
      the war in Kosovo, to assess social functioning, and to identify vulnerable
      populations among ethnic Albanians in Kosovo. DESIGN, SETTING, AND PARTICIPANTS:
      Cross-sectional cluster sample survey conducted from August to October 1999 among
      1358 Kosovar Albanians aged 15 years or older in 558 randomly selected households
      across Kosovo. MAIN OUTCOME MEASURES: Nonspecific psychiatric morbidity,
      posttraumatic stress disorder (PTSD) symptoms, and social functioning using the
      General Health Questionnaire 28 (GHQ-28), Harvard Trauma Questionnaire, and the
      Medical Outcomes Study Short-Form 20 (MOS-20), respectively; feelings of hatred
      and a desire for revenge among persons surveyed as addressed by additional
      questions. RESULTS: Of the respondents, 17.1% (95% confidence interval [CI],
      13.2%-21.0%) reported symptoms that met Diagnostic and Statistical Manual of
      Mental Disorders, Fourth Edition criteria for PTSD; total mean score on the GHQ
      28 was 11.1 (95% CI, 9.9-12.4). Respondents reported a high prevalence of
      traumatic events. There was a significant linear decrease in mental health status
      and social functioning with increasing amount of traumatic events (P</=.02 for
      all 3 survey tools). Populations at increased risk for psychiatric morbidity as
      measured by GHQ-28 scores were those aged 65 years or older (P =.006), those with
      previous psychiatric illnesses or chronic health conditions (P<.001 for both),
      and those who had been internally displaced (P =.009). Populations at risk for
      poorer social functioning were living in rural areas (P =.001), were unemployed
      (P =.046) or had a chronic illness (P =.01). Respondents scored highest on the
      physical functioning and role functioning subscales of the MOS-20 and lowest on
      the mental health and social functioning subscales. Eighty-nine percent of men
      and 90% of women reported having strong feelings of hatred toward Serbs. Fifty
      one percent of men and 43% of women reported strong feelings of revenge; 44% of
      men and 33% of women stated that they would act on these feelings. CONCLUSIONS:
      Mental health problems and impaired social functioning related to the recent war
      are important issues that need to be addressed to return the Kosovo region to a
      stable and productive environment. JAMA. 2000;284:569-577

PMID- 10918703
TI  - Mental health and nutritional status among the adult Serbian minority in Kosovo.
AB  - CONTEXT: Since the beginning of the North Atlantic Treaty Organization
      intervention in Kosovo in June 1999, few objective data have been available on
      relevant health indicators for the Serbian ethnic minority in Kosovo. OBJECTIVE:
      To determine the prevalence of undernutrition among Serbian adults aged 60 years
      or older and psychiatric morbidity among the adult Serbian population in Kosovo.
      DESIGN, SETTING, AND PARTICIPANTS: A systematic random sample survey of 212
      households was conducted between September 27 and October 2, 1999, in Pristina,
      the capital city, and in 10 towns in the rural municipality of Gnjilane in
      Kosovo. Of the 212 households surveyed, 204 adults aged 15 years or older
      completed the General Health Questionnaire-28 (GHQ-28) and anthropometric
      measurements were taken for 98 adults aged 60 years or older and for a comparison
      group of 51 adults aged 18 to 59 years. MAIN OUTCOME MEASURES: Body mass index of
      less than 18.5 kg/m(2) in older adults; nonspecific psychiatric morbidity among
      adults; and self-reported use of health care services, access to food rations,
      and primary sources of prewar and postwar income. RESULTS: Undernutrition was
      found in 11.2% (95% confidence interval [CI], 5.7%-19.2%) of Serbian adults aged
      60 years or older compared with 2.0% (95% CI, 0.1%-11.8%) of Serbian adults aged
      18 to 59 years. The mean (SE) total score for the GHQ-28 was 13.0 (0.52). In a
      comparison of the GHQ-28 scores of the Serbian adults with the Kosovar Albanian
      adults (data from a recent survey), the mean (SE) score adjusted for age and sex
      was 12.8 (0.52) vs 11.1 (0.58); P =.03, respectively. The GHQ-28 scores were also
      higher for the Serbians in the subcategories of social dysfunction (2.8 [0.17] vs
      2.2 [0.13]; P =.008) and severe depression (1.9 [0.15] vs 0.9 [0. 09]; P<.001),
      respectively. Serbian women and persons living alone or in small family units
      were more prone to psychiatric morbidity. Of the 141 respondents reporting the
      need for health care services, 83 (57.6%) reported not obtaining such services;
      204 of 212 (96.2%) households were on a food distribution list. The majority of
      prewar income came from government jobs compared with farming and humanitarian
      aid for postwar income. CONCLUSIONS: The undernutrition of older Serbian adults
      in Kosovo should be monitored. The high prevalence of symptoms of social
      dysfunction and severe depression suggest the need for implementation of mental
      health programs in the Serbian community. JAMA. 2000;284:578-584

PMID- 10918704
TI  - Homicide and suicide rates associated with implementation of the Brady Handgun
      Violence Prevention Act.
AB  - CONTEXT: In February 1994, the Brady Handgun Violence Prevention Act established
      a nationwide requirement that licensed firearms dealers observe a waiting period
      and initiate a background check for handgun sales. The effects of this act have
      not been analyzed. OBJECTIVE: To determine whether implementation of the Brady
      Act was associated with reductions in homicide and suicide rates. DESIGN AND
      SETTING: Analysis of vital statistics data in the United States for 1985 through
      1997 from the National Center for Health Statistics. MAIN OUTCOME MEASURES: Total
      and firearm homicide and suicide rates per 100,000 adults (>/=21 years and >/=55
      years) and proportion of homicides and suicides resulting from firearms were
      calculated by state and year. Controlling for population age, race, poverty and
      income levels, urban residence, and alcohol consumption, the 32 "treatment"
      states directly affected by the Brady Act requirements were compared with the 18
      "control" states and the District of Columbia, which had equivalent legislation
      already in place. RESULTS: Changes in rates of homicide and suicide for treatment
      and control states were not significantly different, except for firearm suicides
      among persons aged 55 years or older (-0.92 per 100,000; 95% confidence interval
      [CI], -1.43 to -0.42). This reduction in suicides for persons aged 55 years or
      older was much stronger in states that had instituted both waiting periods and
      background checks (-1.03 per 100,000; 95% CI, -1.58 to -0.47) than in states that
      only changed background check requirements (-0.17 per 100,000; 95% CI, -1.09 to
      0.75). CONCLUSIONS: Based on the assumption that the greatest reductions in fatal
      violence would be within states that were required to institute waiting periods
      and background checks, implementation of the Brady Act appears to have been
      associated with reductions in the firearm suicide rate for persons aged 55 years
      or older but not with reductions in homicide rates or overall suicide rates.
      However, the pattern of implementation of the Brady Act does not permit a
      reliable analysis of a potential effect of reductions in the flow of guns from
      treatment-state gun dealers into secondary markets. JAMA. 2000;284:585-591

PMID- 10918705
TI  - Pituitary-adrenal and autonomic responses to stress in women after sexual and
      physical abuse in childhood.
AB  - CONTEXT: Evidence suggests that early adverse experiences play a preeminent role
      in development of mood and anxiety disorders and that corticotropin-releasing
      factor (CRF) systems may mediate this association. OBJECTIVE: To determine
      whether early-life stress results in a persistent sensitization of the
      hypothalamic-pituitary-adrenal axis to mild stress in adulthood, thereby
      contributing to vulnerability to psychopathological conditions. DESIGN AND
      SETTING: Prospective controlled study conducted from May 1997 to July 1999 at the
      General Clinical Research Center of Emory University Hospital, Atlanta, Ga.
      PARTICIPANTS: Forty-nine healthy women aged 18 to 45 years with regular menses,
      with no history of mania or psychosis, with no active substance abuse or eating
      disorder within 6 months, and who were free of hormonal and psychotropic
      medications were recruited into 4 study groups (n = 12 with no history of
      childhood abuse or psychiatric disorder [controls]; n = 13 with diagnosis of
      current major depression who were sexually or physically abused as children; n =
      14 without current major depression who were sexually or physically abused as
      children; and n = 10 with diagnosis of current major depression and no history of
      childhood abuse). MAIN OUTCOME MEASURES: Adrenocorticotropic hormone (ACTH) and
      cortisol levels and heart rate responses to a standardized psychosocial
      laboratory stressor compared among the 4 study groups. RESULTS: Women with a
      history of childhood abuse exhibited increased pituitary-adrenal and autonomic
      responses to stress compared with controls. This effect was particularly robust
      in women with current symptoms of depression and anxiety. Women with a history of
      childhood abuse and a current major depression diagnosis exhibited a more than 6
      fold greater ACTH response to stress than age-matched controls (net peak of 9.0
      pmol/L [41.0 pg/mL]; 95% confidence interval [CI], 4.7-13.3 pmol/L [21.6-60. 4
      pg/mL]; vs net peak of 1.4 pmol/L [6.19 pg/mL]; 95% CI, 0.2-2.5 pmol/L [1.0-11.4
      pg/mL]; difference, 8.6 pmol/L [38.9 pg/mL]; 95% CI, 4.6-12.6 pmol/L [20.8-57.1
      pg/mL]; P<.001). CONCLUSIONS: Our findings suggest that hypothalamic-pituitary
      adrenal axis and autonomic nervous system hyperreactivity, presumably due to CRF
      hypersecretion, is a persistent consequence of childhood abuse that may
      contribute to the diathesis for adulthood psychopathological conditions.
      Furthermore, these results imply a role for CRF receptor antagonists in the
      prevention and treatment of psychopathological conditions related to early-life
      stress. JAMA. 2000;284:592-597

PMID- 10918706
TI  - Fatality trends in United Nations Peacekeeping Operations, 1948-1998.
AB  - CONTEXT: The rising number of deaths among United Nations (UN) peacekeeping
      forces after the Cold War has made some troop-contributing countries hesitant to
      participate in peacekeeping operations. While the number and scale of missions
      have increased, no data have demonstrated a parallel increase in risks to
      peacekeepers. OBJECTIVE: To determine the association of characteristics of UN
      peacekeeping operations with risks and mortality rates among UN peacekeeping
      forces in both the Cold War and post-Cold War periods. DESIGN, SETTING, AND
      PARTICIPANTS: Descriptive analysis of 1559 personnel deaths during 49 UN
      peacekeeping missions from 1948-1998 based on the casualty database maintained by
      Department of Peacekeeping Operations, UN Headquarters. MAIN OUTCOME MEASURES:
      Number and percentage of deaths by circumstance, total crude death rate, and
      crude death rate and relative risk of death by circumstance (hostile acts,
      unintentional violence, and illness or other causes) and time period (Cold War vs
      post-Cold War), geographic region, and nature of peacekeeping response; and
      regression analysis of mission variables (strength, duration, and humanitarian
      mandate) associated with total number of deaths. RESULTS: More deaths have
      occurred among UN peacekeeping forces in the past decade alone than in the
      previous 40 years of UN peacekeeping (807 vs 752), but crude death rates did not
      differ significantly by time period (Cold War vs post-Cold War, 21.8 vs 21. 2
      deaths per 10,000 person-years; P =.58), level of peacekeeping response, or for
      geographic regions other than East Europe and Central America, where rates were
      lower (P<.001 for both regions). Unintentional violence accounted for 41.2% of
      deaths, followed by hostile acts (36.1%), and illness or other causes (22.7%).
      Deaths from hostile acts increased after the Cold War (relative risk [RR] 1. 51;
      95% confidence interval [CI], 1.22-1.88), while rates for deaths caused by
      unintentional violence decreased (RR, 0.79; 95% CI, 0.67-0. 94) but remain high,
      particularly in the Middle East and Asia (RR, 1. 39; 95% CI, 1.15-1.69).
      Regression analysis showed a significant association between number of deaths and
      the strength (P<.001) and duration (P<.001) of a peacekeeping mission.
      CONCLUSION: The increase in number of deaths among UN peacekeeping personnel
      since 1990 can be attributed to the increased number and scale of missions after
      the Cold War rather than increased RR of death. Post-Cold War peacekeeping
      personnel have a higher risk of dying from hostile acts in missions where more
      force is required. In missions providing or facilitating humanitarian assistance,
      both the RR of deaths from all causes and deaths from hostile acts are increased.
      JAMA. 2000;284:598-603

PMID- 10918707
TI  - Policies of deterrence and the mental health of asylum seekers.
AB  - In the past, most refugees who permanently resettled in the traditional recipient
      countries of North America, Europe, and Australasia were screened prior to
      arrival in a host country. In the last decade, increasing numbers of unauthorized
      refugees or asylum seekers, those who formally lodge application for refugee
      status in the country in which they are residing, have applied for protection
      after crossing the borders of these countries. Concerns about uncontrolled
      migration have encouraged host countries to adopt policies of deterrence in which
      increasingly restrictive measures are being imposed on persons seeking asylum.
      These measures include, variously, confinement in detention centers, enforced
      dispersal within the community, the implementation of more stringent refugee
      determination procedures, and temporary forms of asylum. In several countries,
      asylum seekers living in the community face restricted access to work, education,
      housing, welfare, and, in some situations, to basic health care services.
      Allegations of abuse, untreated medical and psychiatric illnesses, suicidal
      behavior, hunger strikes, and outbreaks of violence among asylum seekers in
      detention centers have been reported. Although systematic research into the
      mental health of asylum seekers is in its infancy, and methods are limited by
      sampling difficulties, there is growing evidence that salient postmigration
      stress facing asylum seekers adds to the effect of previous trauma in creating
      risk of ongoing posttraumatic stress disorder and other psychiatric symptoms. The
      medical profession has a role in educating governments and the public about the
      potential risks of imposing excessively harsh policies of deterrence on the
      mental health of asylum seekers. JAMA. 2000;284:604-611

PMID- 10918708
TI  - Recognizing the public health impact of genocide.

PMID- 10918709
TI  - Health of Albanians and Serbians following the war in Kosovo: studying the
      survivors of both sides of armed conflict.

PMID- 10918710
TI  - Tracing the Brady Act's connection with homicide and suicide trends.

PMID- 10918711
TI  - Human rights in the biomedical literature: the social responsibility of medical
      journals.

PMID- 10918712
TI  - Short-term prognosis in severe adult and adolescent malnutrition during famine:
      use of a simple prognostic model based on counting clinical signs.
AB  - CONTEXT: In the setting of famine, infection is likely to cause mortality among
      severely malnourished persons. Although clinical signs are likely to be useful
      prognostic indicators in this setting, use of a clinical assessment model has not
      been studied. OBJECTIVE: To examine the use of clinical signs in the prediction
      of short-term mortality in severely malnourished adults and adolescents during
      famine. DESIGN: Retrospective cohort study. SETTING: Concern Worldwide Adult
      Therapeutic Feeding Center in Baidoa, Somalia. PATIENTS: Data from the clinical
      records of 383 adult and adolescent inpatients admitted to the center between
      November 1992 through March 1993 who were aged 15 years or older and had a body
      mass index (BMI) of 13.5 kg/m(2) or less or any signs of edematous malnutrition.
      MAIN OUTCOME MEASURES: Association of mortality with presence or absence of 8
      clinical signs (edema, hydration, ascites, dysentery, diarrhea, anemia, chest
      infection, and ability to stand) and BMI at admission, and sensitivity and
      specificity of models including a count of clinical signs and BMI in the
      prediction of mortality at the center. RESULTS: Ninety-one patients (23.8%) died,
      with a median time to death of 8 days from admission. Of the 8 clinical signs,
      severe edema (unadjusted odds ratio [OR], 2.45; 95% confidence interval [CI],
      1.41-4.27), apparent dehydration (unadjusted OR, 2. 73; 95% CI, 1.60-4.66), and
      inability to stand (unadjusted OR, 2.96; 95% CI, 1.40-6.26) were independently
      associated with mortality. The most useful clinical model was that based on the
      presence of any 1 of these 3 signs, with a sensitivity of 77% and a specificity
      of 59%. Ability of admission BMI to predict mortality was less than random.
      CONCLUSIONS: Models based on clinical signs predicted death better than BMI.
      Simple counts of clinical signs performed as well as more complex models based on
      the addition of ORs. Counting relevant clinical signs is an easy and effective
      prognostic tool in severe adult and adolescent malnutrition during famine;
      however, it is not sensitive enough for use as a screening tool. JAMA.
      2000;284:621-626

PMID- 10918713
TI  - Gastroenterology on the Internet--III.

PMID- 10918714
TI  - The science, law and ethics of fashioning and refashioning endoscopic
      accessories.

PMID- 10918715
TI  - Esophageal and gastric dysmotility in non ulcer dyspepsia.
AB  - BACKGROUND: The pathophysiology of non ulcer dyspepsia is poorly understood. Data
      on gastrointestinal motility alterations in this condition in the Indian
      population are scanty. We studied esophageal and gastric motility in patients
      with non ulcer dyspepsia. METHODS: 58 consecutive patients with non ulcer
      dyspepsia (according to the Rome criteria) were studied; 10 healthy volunteers
      were studied as controls. Esophageal transit of solid and liquid boluses (in all
      patients) and solid-phase gastric emptying (in 20 patients) were studied using
      scintigraphic techniques. RESULTS: Delayed esophageal transit and delayed gastric
      emptying were observed in 32 (55%) and 9 (45%) patients, respectively. Delay of
      both esophageal and gastric transit was found in 5 patients. Mean (SD) esophageal
      transit for liquid bolus was significantly delayed in patients (9.3 [3.7] s)
      compared to controls (7.0 [2.0] s; p < 0.01). Mean (SD) gastric emptying time
      (T50) was significantly delayed in patients (61.6 [13.6] min) compared to
      controls (50.0 [5.0] min; p < 0.001). Esophageal and gastric delayed transit was
      found in about two thirds of patients with dysmotility-like dyspepsia, but there
      were no significant difference in these abnormalities among different subgroups
      of dyspepsia. CONCLUSION: High prevalence of esophageal and gastric transit delay
      was found in non ulcer dyspepsia, particularly in the dysmotility subgroup.

PMID- 10918716
TI  - Oxidative stress in liver of mice exposed to arsenic-contaminated water.
AB  - BACKGROUND: Oxidative stress has been implicated in the initiation of hepatic
      damage caused by various agents. Not much data on oxidative stress in liver in
      chronic arsenic exposure are available in the literature. We therefore studied
      this aspect in a murine model. METHODS: BALB/c mice were given arsenic
      contaminated (3.2 mg/L) or arsenic-free (< 0.01 mg/L, control) drinking water ad
      libitum. Batches of mice were sacrificed after 2 and 4 months, and blood samples
      and liver tissue were collected. Liver histology was examined and levels of
      hepatic reduced glutathione (GSH), malondialdehyde, and enzymes of the
      antioxidant defense system in the liver tissue were determined. Arsenic content
      in liver tissues obtained at 4 months was estimated. RESULTS: Two-month exposure
      to arsenic caused significant elevation of hepatic GSH (11.4 [0.8] micrograms/mg
      protein) compared to control mice (9.3 [0.4]; p < 0.01). Levels of enzymes
      related to GSH homeostasis were also elevated. At 4 months, hepatic GSH was
      significantly reduced (8.4 [0.5] micrograms/mg protein) when compared to control
      mice (9.3 [0.4]; p < 0.01). Arsenic content in the liver tissue after 4 months of
      exposure was significantly higher (0.40 [0.05] microgram/g) as compared to
      control mice (0.04 [0.04]; p < 0.01). CONCLUSION: The results suggest that the
      antioxidant defense system in the liver of mice is activated after exposure to
      arsenic for 2 months. However, prolonged exposure to arsenic probably causes
      overuse failure of this system, which might result in initiation of biochemical
      injury to the liver.

PMID- 10918717
TI  - Precut papillotomy using needle knife fashioned from discarded standard
      papillotomes.
AB  - AIM: To evaluate the results of precut papillotomy using needle-knife
      papillotomes fashioned from discarded standard sphincterotomes. METHODS: Case
      records of 50 patients undergoing precut papillotomy for access to either common
      bile duct or pancreatic duct during endoscopic retrograde
      cholangiopancreatography were reviewed. Precut was performed using needle-knife
      papillotomes fashioned from standard pull-type sphicterotomes that were discarded
      because of broken cutting wires. A diagnostic procedure was planned in all 50
      patients (bile duct = 39, pancreatic duct = 9, both ducts = 2) and therapeutic
      procedure in 36 patients (bile duct = 31, pancreatic duct = 5). RESULTS: Of the
      47 patients who needed precut prior to diagnostic ERCP, 44 (93.6%) underwent
      successful cannulation of the duct of choice. Therapeutic procedures were planned
      in 36 patients; these were successful in 24 (67%; bile duct = 22, pancreatic duct
      = 2). The complications included cholangitis in 8 patients (16%) and pancreatitis
      in 2 (4%). None had bleeding or perforation. CONCLUSIONS: Precut needle-knife
      papillotomes fashioned from discarded standard sphincterotomes can be used
      effectively and can help in cost containment in endoscopic retrograde
      cholangiopancreatography.

PMID- 10918718
TI  - Development of an animal model of hepatic fibrosis by excretory-secretory antigen
      of Ascaris suum.
AB  - OBJECTIVE: The excretory-secretory (ES) antigens of Ascaris suum are known to
      cause hepatic damage in animals. The present study was aimed at developing an
      animal model of hepatic fibrosis with these antigens. METHODS: Three doses of ES
      antigens of A. suum were injected into 24 golden hamsters on days 0, 10 and 20.
      Batches of 8 animals each were sacrificed at 3 days, 45 days and 90 days after
      the third injection, after collection of blood. Three groups of 6 control animals
      each were injected with normal saline and were sacrificed similarly. Liver
      biochemistry, leukocyte migration inhibition test on cells separated from spleen,
      and liver histology were carried out. RESULTS: Serum ALT levels in experimental
      animals were significantly higher than those in control animals at days 3, 45 and
      90 after the last antigen dose; AST levels were elevated 45 and 90 days after the
      last dose of ES antigen. Leukocyte migration inhibition in experimental animals
      was 58.2 (8.5)%, 51.6 (11.2)% and 50.5 (12.8)% at days 3, 45 and 90 after the
      last antigen dose. Marked centrivenular degeneration and necrosis were observed
      in liver tissue in all the experimental animals sacrificed 72 h after the last
      antigen dose. Condensation of reticulin around the portal zone with extension
      into the liver lobule was observed in 4 of 8 and 7 of 8 experimental animals
      sacrificed 45 and 90 days, respectively, after the last dose. Control animals did
      not have such lesions. CONCLUSION: An animal model of hepatic fibrosis could be
      produced by repeated injection of ES antigens of A. suum.

PMID- 10918719
TI  - Autonomic nervous system reactivity in irritable bowel syndrome.
AB  - BACKGROUND: Autonomic dysfunction has been implicated as one of the factors
      involved in the pathogenesis of irritable bowel syndrome (IBS). AIM: To evaluate
      autonomic function in patients with IBS. METHODS: Thirty-five patients with IBS
      and thirty healthy controls were evaluated by standard cardiovascular reflex
      tests. Parasympathetic function was assessed by measuring heart rate responses to
      deep and slow breathing (E:I ratio), Valsalva maneuver (Valsalva ratio) and head
      up tilt tests (30:15 ratio). Sympathetic adrenergic function was assessed by
      measuring diastolic blood pressure responses to handgrip test at 4 min and cold
      pressor test at 1 min and also by change in systolic blood pressure in response
      to head-up tilt. Autonomic functions were tested twice, keeping at least a one
      week interval, to find out stability over time. Anxiety status of the subjects
      was assessed by evaluating responses to a questionnaire. RESULTS: Parasympathetic
      reactivity was significantly increased in IBS patients as compared to controls
      during visit 1 (E:I 1.7 [SD 0.2] vs 1.4 [0.1], p < 0.001; Valsalva ratio 2.0
      [0.3] vs 1.5 [0.1], p < 0.001; 30:15 ratio 1.2 [0.1] vs 1.1 [0.01], p < 0.001).
      Similar results were obtained in visit 2. The diastolic blood pressure responses
      during handgrip and cold pressor tests were not different in comparison to
      controls during both the visits. However, tilting resulted in less marked rise in
      diastolic blood pressure (9.1 [4.1] vs 12.1 [6.8] mmHg, p < 0.01) at 0.5 min and
      less rise in heart rate (6.0 [2.5] vs 10.3 [6.3] per min, p < 0.01) at 1 min in
      IBS patients during visit 1. The anxiety score of IBS patients was significantly
      higher (46.2 [3.2] vs 21.6 [1.7], p < 0.001). CONCLUSION: IBS patients have
      increased parasympathetic reactivity and a high level of anxiety trait.

PMID- 10918720
TI  - Predictors of response to pneumatic dilatation in achalasia cardia.
AB  - BACKGROUND: The role of esophageal laboratory testing in predicting response to
      balloon dilatation in patients with achalasia cardia has been evaluated in the
      West; data in Indian patients are scant. AIM: To study the predictors of response
      to pneumatic balloon dilatation in Indian patients with achalasia cardia.
      METHODS: Twenty-five patients with achalasia cardia who had earlier undergone
      esophageal manometry before balloon dilatation (Group A) were recalled for
      clinical evaluation. Another consecutive 25 patients with newly diagnosed
      achalasia (Group B) underwent esophageal manometry and isotope transit studies
      before and after dilatation. RESULTS: The overall symptom response to dilatation
      in the 50 patients at median (range) follow up of 26 (1-60) months was 64%. Pre
      dilatation clinical and laboratory parameters did not predict outcome. All
      patients with 1-week post-dilatation lower esophageal sphincter (LES) basal
      pressure less than or equal to 10 mmHg and residual pressure less than 6 mmHg
      were asymptomatic at follow up. CONCLUSION: Post-dilatation LES basal pressure
      less than or equal to 10 mmHg and residual pressure less than 6 mmHg are
      predictors of symptom response to balloon dilatation in patients with achalasia
      cardia.

PMID- 10918721
TI  - Hepatitis B virus: infected or just carrying?

PMID- 10918722
TI  - Paraesophageal mediastinal drainage with diversion for delayed presentation of
      esophageal perforation.
AB  - Esophageal perforation is a serious condition; a delay of more than 48 hours in
      initiation of treatment leads to increased morbidity and mortality. Management of
      such patients is a surgical dilemma. We successfully managed 4 patients (2
      iatrogenic, 1-tuberculous, 1-Boerhaave's syndrome) with delayed presentation of
      esophageal perforation by esophageal exclusion and paraesophageal mediastinal
      drainage, achieving good control of mediastinal sepsis, healing of perforation
      and at the same time avoiding thoracotomy and subsequent second surgery.

PMID- 10918723
TI  - Xanthelasma of esophagus and stomach.
AB  - Gastric xanthelasma, a benign condition, has been reported before; there has been
      no documentation of xanthelasma of the esophagus. We report a patient with
      xanthelasma of the stomach and esophagus.

PMID- 10918724
TI  - Reversible portal hypertension due to tuberculosis.
AB  - Presentation of abdominal tuberculosis with portal hypertension is rare. We
      report a 25-year-old man with portal hypertension due to compression of the
      portal vein by tuberculous lymph nodes at the hepatic hilum. After antitubercular
      therapy, features of portal hypertension disappeared as the nodes regressed.

PMID- 10918726
TI  - Anomalous bile duct injury during laparoscopic cholecystectomy.
AB  - We report a patient in whom the common hepatic duct drained into the gall bladder
      body and the cystic duct continued as the bile duct into the duodenum. The
      anomalous duct was inadvertently injured during laparoscopic cholecystectomy. The
      injury was repaired and end-to-end anastomosis of the hepatic and cystic ducts
      was done through a subcostal incision.

PMID- 10918725
TI  - Primary hypertrophic colonopathy.
AB  - We report a 45-year-old man and a 60-year-old woman who presented with features
      of intermittent intestinal obstruction. Barium enema revealed narrowing at the
      pelvic-rectal junction in the man, and from the pelvic colon to the anal verge in
      the woman. Histology of the resected sections showed marked hypertrophy of the
      muscularis propria in both cases, with normal mucosa, submucosa and myenteric
      plexus. Both patients are asymptomatic at 4 years' and 2 years' follow up. This
      entity of primary hypertrophic colonopathy may be a variant of primary visceral
      myopathy.

PMID- 10918727
TI  - Gastric angina secondary to acute thrombosis of celiac artery.
AB  - We report a 48-year-old woman with foregut ischemia with splenic infarct due to
      isolated celiac artery obstruction. The patient presented with acute-onset pain
      in the epigastrium 10-15 min after every meal. Investigations revealed
      obstruction of the celiac artery by artheromatous plaque. This patient had an
      acute thrombosis, which responded to anticoagulation.

PMID- 10918728
TI  - Enteric duplication cyst associated with melanosis peritonei.
AB  - Melanosis peritonei is usually associated with benign cystic teratomas of the
      ovary. We describe a one-and-a-half-year-old girl with melanosis peritonei
      associated with enteric duplication cyst. Melanophages were seen in aggregates in
      and around the serosal blood vessels, nerve bundles, and scattered within the
      muscular wall of the cyst. Presence of hyperplastic nerve bundles associated with
      melanophages suggests their origin from the neural crest.

PMID- 10918730
TI  - Skip lesions in ulcerative colitis.

PMID- 10918729
TI  - Paraganglionoma of extrahepatic biliary tract causing obstructive jaundice.
AB  - We report a young woman with paraganglionoma arising from the extrahepatic bile
      duct presenting with acute obstructive jaundice. The patient underwent excision
      of the gall bladder and extrahepatic bile duct with the tumor, and Roux-en-Y
      hepaticojejunostomy. She is asymptomatic 9 months later, with normal biochemical
      investigations and imaging.

PMID- 10918731
TI  - Lipoprotein (a) in ulcerative colitis.

PMID- 10918732
TI  - Meckel's diverticulum presenting as acute abdomen in children.

PMID- 10918733
TI  - Implantation of Mousseau-Barbin tube for 13 years.

PMID- 10918734
TI  - Hepatic vein thrombosis with ulcerative colitis.

PMID- 10918735
TI  - Hepatocellular carcinoma presenting as soft tissue mass in gluteal region.

PMID- 10918736
TI  - Colonic carcinoma presenting with metastasis to finger.

PMID- 10918737
TI  - Heat trauma: a cause for esophageal ulcer?

PMID- 10918738
TI  - Double-shot magnetic resonance imaging of cerebral lesions: fast spin-echo versus
      echo planar sequences.
AB  - The authors compared two new rapid MRI techniques: double-shot echo-planar
      imaging (DS-EPI) versus double-shot fast spin-echo (DS-FSE) in the evaluation of
      cerebral lesions. The authors examined 35 patients with 37 lesions, which were
      hyperintense on long TR images. Patients were scanned with both DS-EPI and DS-FSE
      with a time of repetition (TR) of 10,000 milliseconds and an echo time (TE) of 80
      milliseconds. Conspicuity was determined from region of interest measurements to
      calculate contrast to noise ratio (C/N). Visual comparisons between DS-EPI and DS
      FSE, and between DS-EPI and T2-weighted conventional spin-echo (CSE) were also
      performed to evaluate the sequences' ability to depict hemorrhage. The mean C/N
      for both sequences was comparable: 36.7 for DS-FSE and 35.6 for DS-EPI, with no
      statistically significant difference (p = 0.77). With regards to depicting blood
      products, DS-EPI proved far more effective than DS-FSE and comparable to CSE.
      Also, DS-EPI proved to be more time-efficient, requiring 1.67 seconds per
      section, while DS-FSE required 3.33 seconds per section. Whereas DS-FSE and DS
      EPI are comparable in their ability to depict hyperintense cerebral pathology, DS
      EPI is more time-efficient, and therefore appears preferable. Because of the high
      magnetic susceptibility of DS-EPI, geometric distortion degrades visualization of
      lesions in the posterior fossa or near the sinuses. On the other hand, the high
      magnetic susceptibility results in high conspicuity of blood products.

PMID- 10918739
TI  - Phakomatoses. Part I: Neurofibromatosis type 1: common and uncommon neuroimaging
      findings.
AB  - Neurofibromatosis type I (NF-1) belongs to a family of diseases named
      phakomatoses, which are characterized by congenital malformations of ectodermal
      structures. Neurofibromatosis type I affects 1 in 3000 people, and has a diverse
      clinical presentation as well as an array of imaging findings. In this article
      the authors review the various neuroimaging findings present in NF-1, including
      abnormalities of the parenchyma, meninges, vessels, and associated neoplasms.

PMID- 10918740
TI  - Feasibility of brain volumetric analysis and reconstruction of images by
      transfontanel three-dimensional ultrasound.
AB  - Based on the authors' experience with reconstruction of the heart using three
      dimensional echocardiography, the authors assessed the feasibility of three
      dimensional reconstruction of brain images using transfontanelle ultrasound in
      selected cases of infants with abnormal intracranial findings. A conventional 5
      MHz ultrasound transducer inside a transducer holder was rotated 180 degrees
      around its vertical axis using a computer-controlled stepper motor to acquire
      multiple sequential cross-sections of the brain. The raw digital data of this
      three-dimensionally recorded dataset were transferred to a PC-based workstation
      for further analysis. The reconstruction of the three-dimensional brain images
      and volumetric analysis were undertaken using a new dedicated software capable of
      three-dimensional reconstruction and volumetric analysis (Echo-PAC-3D, version
      1.2 Beta, GE Vingmed, Horton, Norway). The reconstruction of sequential slices
      from the stored three-dimensional data allowed the visualization of the
      epicortical extension and volumetric measurements of the focal ischemic
      infarction in the superior tempoparietal lobe in a 2-week-old newborn with a
      focal ischemic brain lesion. In other 2-week-old newborns, the extension and
      volume of a periventricular hemorrhage was visualized by three-dimensional
      reconstruction of coronal cross-sectional images from the acquired three
      dimensional dataset. The three-dimensional reconstruction of the lateral
      ventricles allowed the three-dimensional visualization and estimation of
      ventricular dilatation in milliliters in an 8-week-old infant with hydrocephalus.
      Three-dimensional reconstruction of brain images and volume estimation of brain
      lesions and cavities by ultrasound may provide new insights into the morphology
      and extension of ultrasonographically visible brain lesions.

PMID- 10918741
TI  - Gender-related differences in acetazolamide-induced cerebral vasodilatory
      response: a transcranial Doppler study.
AB  - Cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity
      acceleration can be easily and reliably assessed by measuring acetazolamide
      induced changes using transcranial Doppler. The authors' aim was to determine
      whether there are gender-related differences in these parameters. Fifty-six
      healthy subjects (27 males, 29 females) were examined using transcranial Doppler.
      Velocities in the middle cerebral artery on both sides were recorded before and
      at 5, 10, 15, and 20 minutes after intravenous administration of 1 g
      acetazolamide. The baseline mean flow velocity in the middle cerebral artery was
      significantly higher in women than in men (p < 0.02). After acetazolamide
      administration, significantly higher cerebrovascular reactivity, cerebrovascular
      reserve capacity, and velocity acceleration were observed in females than in
      males (p < 0.001 in all cases). Subgroup analysis showed that women before
      menopause responded with higher cerebrovascular reserve capacity and velocity
      acceleration than age-matched men (p < 0.01 and p < 0.001, respectively), but no
      significant difference was found between females after menopause and men of
      similar age.

PMID- 10918742
TI  - Blood flow velocities in middle cerebral artery branches after subarachnoid
      hemorrhage.
AB  - In a prospective study, 55 patients were examined by transcranial duplex
      sonography (TCCS) after subarachnoid hemorrhage (SAH) to determine whether
      additional transcranial duplex examination on the middle cerebral artery M2
      segments would aid in the examination of the MCA stem segment. The mean blood
      flow velocities and pulsatility index were correlated to the occurrence of
      delayed ischemic neurologic deficits (DIND). Out of 47 patients included, 21 did
      not experience any delayed deficit (group I), 15 did (group II), and in 11 the
      extent to which vasospasm contributed to a neurologic deficit was unclear (group
      III). The highest blood flow velocity and the greatest increase of mean blood
      flow velocity on 1 day were significantly higher in groups II and III both in M1
      and in M2. In 10 patients in group II, where the onset day of DIND was known
      exactly, Doppler data indicating ischemia before or at the time of DIND were
      observed in nine. In eight patients, Doppler of the MCA stem alone would have
      provided enough information to recognize the risk of symptomatic vasospasm; in
      one patient, only the M2 Doppler gave an indication of ischemic complication.
      Transcranial duplex sonography may provide additional information to TCD by
      accurate delineation of M1/M2 vasospasm and therefore may help plan cerebral
      angiography and neurointerventional treatment.

PMID- 10918743
TI  - Regional cerebral distribution of [Tc-99m] hexylmethylpropylene amineoxine in
      patients with progressive aphasia.
AB  - Progressive aphasia is a prominent clinical feature of several neurodegenerative
      disorders. This study used hexylmethylpropylene amineoxine (HMPAO) single photon
      emission computed tomography (SPECT) to estimate blood flow in areas of the brain
      that mediate language in patients with progressive aphasia and matched control
      subjects. The patient population consisted of four men and 12 women with a mean
      +/- SD age of 69.1 +/- 7.6. Of these, eight were classified as having a nonfluent
      form of aphasia, whereas the other eight had a fluent form. The patients were
      compared to 16 healthy volunteers who were studied with an identical protocol.
      The SPECT images of the brain were acquired with 740 MBq (20 mCi) of Tc-99m
      labeled HMPAO on a triple-headed gamma camera equipped with fan beam collimators.
      The images were analyzed with a set of standardized templates. Mean counts per
      pixel in 33 regions of interest were compared to the mean counts in the whole
      supratentorial brain. A laterality index was determined for homotopic regions
      using the equation 100 x (R - L)/(1/2 x (R - L)). Patients with progressive
      aphasia had several regions of significantly decreased HMPAO uptake in the left
      cortex when compared to the homotopic regions on the right. The most prominent
      deficit in the nonfluent group, as determined by the laterality index, were found
      in the left dorsolateral prefrontal region (p < 0.05), whereas the most prominent
      deficits in the group with fluent aphasia were found in the left temporal and
      parietal language centers (p < 0.05). The left subcortical nuclei were
      differentially affected, particularly in patients with nonfluent aphasia. The
      HMPAO SPECT indicates that multiple regions of the left hemisphere are
      dysfunctional in patients with progressive aphasia. The pattern of perfusion
      deficits in patients with fluent aphasia appears to be distinct from the pattern
      in patients with nonfluent aphasia.

PMID- 10918744
TI  - Central pontine myelinolysis: delayed changes on neuroimaging.
AB  - The authors report two cases, a 44-year-old woman and a 6-year-old girl who had
      mental status changes and hyponatremia. Serum sodium levels in both of these
      cases were corrected quickly with further decline in their mental status, and the
      patients became quadriparetic. Magnetic resonance imaging (MRI) studies performed
      then did not reveal any abnormalities, whereas a repeat imaging study performed
      10-14 days after the shift in serum sodium revealed evidence for central pontine
      myelinolysis and extrapontine demyelination. The clinical manifestations and
      distribution of lesions seen on the imaging studies demonstrated that the above
      presentation of neurologic illness is the result of hyponatremia and its
      correction. The authors conclude that imaging studies performed early during the
      illness may be unremarkable, but still a diagnosis of central pontine
      myelinolysis should be suspected and, most importantly, a repeat imaging study
      might be required in 10-14 days to establish the diagnosis of central pontine
      myelinolysis.

PMID- 10918745
TI  - Three-dimensional transcranial color-coded sonography for the examination of the
      arteries of the circle of Willis.
AB  - Because examinations of the intracranial vessels using conventional transcranial
      color-coded sonography (TCCS) lack spatial orientation and reproducibility,
      development of a three-dimensional (3-D) imaging technique is required. Three
      patients with middle cerebral artery (MCA) stenosis, three with suspected
      intracranial aneurysm, two with vascular malformation, and one healthy volunteer
      were investigated by 3-D TCCS using a magnetic spatial positioning sensor mounted
      on the transducer for simultaneous recording of the probe coordinates to create a
      volumetric data set. Three-dimensional transcranial color-coded sonography
      enabled good visualization of intracranial aneurysms and MCA stenoses. However,
      it failed to detect morphological details in vascular malformations. In
      conclusion, 3-D TCCS is a promising technique that opens new perspectives in
      depicting intracranial vessels and provides volume measurement of intracranial
      aneurysms.

PMID- 10918746
TI  - Emergency endovascular treatment of cerebral sinus thrombosis with a rheolytic
      catheter device.
AB  - Severe thrombosis of the superior sagittal, transverse, and straight sinuses
      developed in a 53-year-old woman. This resulted in extensive multifocal
      hemorrhagic venous infarction and severe intracranial hypertension refractory to
      intensive management. Endovascular therapy using a rheolytic catheter device in
      combination with a small amount of fibrinolytic agent led to rapid normalization
      of the intracranial pressure, allowing optimization of the cerebral perfusion
      pressures and was followed by steady, albeit protracted, clinical improvement.
      The patient not only survived but also left the hospital with minimal neurologic
      deficit. The rheolytic catheter endovascular treatment is, in the opinion of the
      authors, the treatment of choice for patients with life-threatening cerebral
      sinus thrombosis.

PMID- 10918747
TI  - Orbital involvement as the initial manifestation of sarcoidosis: magnetic
      resonance imaging findings.
AB  - A 74-year-old man had diplopia, painful right ophthalmoplegia, proptosis,
      conjunctival injection, and facial skin lesions. Magnetic resonance imaging (MRI)
      revealed infiltration of the right intraorbital adipose tissue. Lesions were
      mixed low- and high-signal on T2-weighted images and enhanced on fat-suppressed
      T1-weighted postcontrast images. A skin biopsy revealed numerous noncaseating
      granulomas consistent with sarcoidosis. Treatment with corticosteroids and
      chlorambucil led to a full clinical recovery. Sarcoidosis should be considered in
      the evaluation of orbital pseudotumor in elderly patients, even if no systemic
      manifestations of sarcoidosis are present.

PMID- 10918748
TI  - Dural cavernous angioma mimicking a meningioma and causing facial pain.
AB  - An 18-year-old girl who had severe headaches in the left temporal and facial
      regions was found to have a small enhanced dural-based parietal convexity mass.
      On magnetic resonance imaging (MRI), this mass was homogeneously enhanced with
      "dural tail sign," and was similar to a meningioma. This mass was completely
      removed surgically, and pathology proved it to be a cavernous angioma without
      previous hemorrhages. The patient's facial pain was dramatically relieved after
      surgery. A small dural mass causing severe facial pain is an unusual situation.
      The lack of hemosiderin in the extra-axial cavernous angioma often leads to the
      preoperative diagnosis of meningioma.

PMID- 10918749
TI  - Shunt-responsive dementia in sarcoid meningitis: role of magnetic resonance
      imaging and cisternography.
AB  - The authors report a patient with progressive cognitive and gait decline in
      association with sarcoid meningitis. The patient had evidence of active
      inflammation as determined by cerebrospinal fluid examination and was steroid
      dependent. Magnetic resonance imaging and radionucleotide cisternography were
      complementary in establishing the diagnosis of communicating hydrocephalus, and
      suggested that the patient would be shunt responsive.

PMID- 10918750
TI  - Midbrain ptosis caused by periaqueductal infarct following cardiac
      catheterization: early detection with diffusion-weighted imaging.
AB  - Isolated infarcts in the periaqueductal region are rare but have been reported
      after cardiac catheterization. The authors report a case of dorsal midbrain
      infarct which caused bilateral ptosis, partial upgaze paresis, and internuclear
      ophthalmoplegia imaged within eight hours with diffusion-weighted imaging (DWI).
      The lesion was later confirmed on T2-weighted images. Diffusion-weighted imaging
      can rapidly confirm the diagnosis of this rare brain-stem infarct.

PMID- 10918751
TI  - MRI findings in 32 consecutive lipomas using conventional and advanced sequences.

PMID- 10918752
TI  - Medicaid audits.

PMID- 10918753
TI  - Foramen of Morgagni hernia: surgical consideration.
AB  - We have recently encountered two patients with foramen of Morgagni hernias both
      of whom were symptomatic and required repair. Both patients did well following
      repair. Symptomatic Morgagni hernias should be repaired to reduce complications
      in later life.

PMID- 10918755
TI  - "Diagnostic elegance and therapeutic parsimony".

PMID- 10918754
TI  - Pediatric autoimmune cardiovascular disease.
AB  - Pediatric autoimmune cardiovascular disease can cause serious, sometimes life
      threatening sequelae on the pediatric population. Valvular, myocardial, and
      pericardial involvement causing morbidity and mortality can occur in association
      to rheumatic heart disease, systemic lupus erythematosus, and juvenile rheumatoid
      arthritis. Serious and potentially life threatening coronary artery involvement
      can occur in patients with childhood polyarteritis nodosa, Takayasu arteritis,
      and Kawasaki disease.

PMID- 10918756
TI  - The status of primary care in rural Mississippi.

PMID- 10918757
TI  - The development of a stroke clinical pathway: an experience in a medium-sized
      community hospital.
AB  - Patients with acute ischemic strokes were studied in a medium-sized community
      hospital in Mississippi. Studies were done before and after implementation of the
      stroke clinical care pathway with emphasis on the following clinical indicators:
      1) performance of a brain CT scan, 2) the search for the etiology of the stroke,
      3) whether the patient was treated emergently for hypertension, 4) the use of
      measures to prevent deep-vein thrombosis, and 5) prophylactic drug treatment
      against recurrent stroke after hospital discharge. Following application of the
      clinical pathway, there was a significant improvement in all the clinical
      indicators that were felt to require further attention and none had a setback.
      The length of hospital stay was decreased, and there was no significant increase
      in the hospital costs in the post-pathway study despite an increase in the number
      of diagnostic and therapeutic procedures performed. When applied properly,
      clinical pathways can effectively mobilize hospital resources, maximize quality
      of care, and at the same time minimize costs.

PMID- 10918758
TI  - Emergency civil commitment for persons with mental illness.

PMID- 10918759
TI  - Mississippi's bridge builder: Dr. Verner S. Holmes (1909-2000) remembered.

PMID- 10918760
TI  - Relationship between height, glucose intolerance, and hypertension in an urban
      African black adult population: a case for the "thrifty phenotype" hypothesis?
AB  - An association between the factors of low birth weight and fetal growth
      retardation and subsequent risk of cardiovascular disease has been proposed; this
      is the basis of the "thrifty phenotype" hypothesis described in relation to type
      2 diabetes mellitus. The relationship between height, presumably an indicator of
      early life experience, and glucose intolerance and hypertension was examined in a
      sample survey of noncommunicable disease in an urban African adult population.
      Height, other anthropometric measurements, and biosocial data were obtained in
      the study of 998 civil servants selected by multistage sampling in Ibadan, a
      major Nigerian city. Ibadan is a low-prevalence region for diabetes, with a rate
      of 0.8% and 2.2% for an impaired glucose tolerance. The prevalence rate of
      hypertension was 10.3% in the population. A significant negative correlation was
      found between height and blood glucose level (r = -0.14, p < 0.001), whereas
      there was no correlation with blood pressures. Multiple regression analyses did
      not demonstrate height as a determinant of either blood pressure or plasma
      glucose. However, in a logistic model height was found to be associated with
      abnormal glucose tolerance (diabetes and impaired glucose tolerance) (odds ratio,
      0.01; p < 0.003). In the logistic model of the blood pressure data there was no
      association between height and hypertension. There was some association between
      height and blood glucose level and also glucose intolerance in the urban African
      population sample, but none with elevated blood pressure. The significance of the
      observed inverse relationship, though uncertain, deserves further exploration.

PMID- 10918762
TI  - Impact of environmental inequity on health outcome: where is the epidemiological
      evidence?
AB  - A significant amount of evidence reveals a presence of environmental inequity.
      Although there is a disproportionate distribution of waste treatment, storage and
      disposal facilities, and chemical and manufacturing plants in minority and low
      income communities in the United States, little research has been devoted to show
      any associations based on analytic epidemiological methods. To date, attempts to
      quantify health disparities have included demographic data, race, sex, income,
      other socioeconomic factors, and broad symptomatic survey instruments. To study
      this, we examined the latest epidemiological evidence documenting the existence
      of adverse health impacts resulting from environmental inequity. We observed that
      the overwhelming majority of studies were descriptive in nature and lacked
      comparison populations. As a result, we believe that further research based on
      analytic epidemiological methods would further contribute to the determination of
      the cause-effect relationship between environmental exposure and health outcome.

PMID- 10918761
TI  - Perception of reliability of human immunodeficiency virus/AIDS information
      sources.
AB  - The sources of human immunodeficiency virus (HIV)/AIDS information as well as the
      perception of reliability of information from these sources may have a
      significant impact on the effectiveness of HIV risk reduction messages in
      reaching high risk populations. We examined the sources of HIV information and
      the perception of reliability of information from these sources among African
      Americans (n = 441), Hispanic Americans (n = 456), and whites (n = 297), in
      Houston, Texas. The data revealed that African Americans and Hispanics were most
      likely to receive their HIV/AIDS information from the "media" compared with
      whites who received most of their information from "government agencies and
      professionals." Information from "family, friends and schools" were regarded as
      the least reliable by respondents from all three ethnic groups. The data also
      showed that perceptions of reliability of information sources were influenced by
      level of educational attainment. Implications for designing target audience
      specific intervention strategies for the prevention of the spread of HIV disease
      are discussed.

PMID- 10918763
TI  - Changes in radical prostatectomy and radiation therapy rates for African
      Americans and whites.
AB  - There are racial differences in prostate cancer outcomes. One variable
      influencing end results is treatment for cure: either radical prostatectomy (RP)
      or radiation therapy (RT). The purpose of this report is to determine changes in
      diagnosis rates of localized prostate cancer between the years before prostate
      specific antigen (PSA) use (1973-1988) and the years after PSA use (1989-1996),
      to evaluate differences in RP and RT rates between the pre-PSA and post-PSA eras,
      to assess differences in RP and RT rates between African Americans and whites
      between these intervals. The Surveillance, Epidemiology, and End Results (SEER)
      data were used and evaluated. Both African Americans and whites had statistically
      increased rates of localized prostate cancer diagnosed (70.4 and 49.0 in 1973
      through 1988 and 123.1 and 84.9 in 1989 through 1996, respectively [p < 0.05]).
      The differences between the pre-PSA and post-PSA eras for African Americans and
      whites for RP (3.6 vs. 44.3 and 5.0 vs. 44.9, respectively) and RT (23.6 vs. 61.6
      and 17.0 vs. 38.1, respectively) were all significant (p < 0.05). Both African
      Americans and whites had increased rates of RP from 3.6 and 5.0 to 44.3 and 44.9,
      respectively, and RT from 23.6 and 17.0 to 61.6 and 38.1 during the pre- and post
      PSA years.

PMID- 10918765
TI  - Rupture of a cesarean-scarred uterus: a community hospital experience.
AB  - Concerns that a scarred uterus may rupture during labor have contributed to
      increased cesarean rates. A previous cesarean has become one of the most common
      indications for abdominal birth. More women must deliver vaginally after cesarean
      if we are to reduce cesarean rates. This study evaluates the effect of decreasing
      cesarean rates and increased vaginal birth after cesarean (VBAC) rates on the
      incidence of uterine rupture in a community hospital. We studied data for women
      who delivered at our obstetrical unit from 1988 through 1997. During 1994 our
      department adopted strategies to reduce cesarean rates. Data from women who
      delivered from 1988 through 1993 (period A, before the policy change) were
      compared with data for those who delivered from 1994 through 1997 (period B,
      after the policy change) and evaluated by chi-square analysis. p < 0.05 was
      considered significant. The total cesarean rate decreased from 24.3% (period A)
      to 17.9% (period B) (p < 0.0001), whereas the primary cesarean rate decreased
      from 14.9% to 10.3% (p < 0.0001), and the repeat rate decreased from 9.4% to 7.6%
      (p < 0.0001). The VBAC rate increased from 13.0 to 28.6 (p < 0.0001), whereas the
      incidence of uterine rupture did not change. During the study period, the
      cesarean rate decreased while the VBAC rate safely increased. The incidence of
      uterine rupture remained unchanged.

PMID- 10918764
TI  - Bladder cancer: a review of diagnosis and management.
AB  - Bladder cancer is the fourth most commonly diagnosed malignancy in men and the
      eighth most common in women. It represents a spectrum of disease, ranging from
      superficial, well-differentiated disease, which does not significantly impact
      survival, to highly malignant tumors for which long term survival may be dismal.
      Transitional-cell carcinoma, which constitutes the vast majority of bladder
      cancers in the United States, may develop as carcinoma in situ or as invasive
      carcinoma. This article focuses on transitional-cell carcinoma with a review of
      the major aspects of the disease, including the epidemiology, diagnosis and
      staging, and management (including organ preservation). Therapeutic options are
      explored, including surgery, radiotherapy, chemotherapy, and combined modality
      therapy.

PMID- 10918766
TI  - Breast cancer before and during the AIDS epidemic in women and men: a study of
      Tanzanian Cancer Registry Data 1968 to 1996.
AB  - Kaposi's sarcoma and malignant lymphoma are two cancers that are most often
      associated with human immunodeficiency virus (HIV) infection. Recently, other
      cancers, including cervical cancer, have been associated with AIDS. The role of
      HIV in the pathogenesis of these malignancies is not well understood, and few
      studies have been done to determine any general increase in cancers after the
      onset of the HIV epidemic. This study compared breast cancer before and during
      the AIDS period by studying the total Tanzanian Cancer Registry data (1968 to
      1996). The mean age among males increased from 50.88 to 52.63 years (p = 0.45)
      and among females decreased from 44.79 to 43.23 years (p = 0.005) before and
      during the AIDS epidemic, respectively. A statistically significant decrease in
      the incidence of breast cancer was observed during the AIDS epidemic period in
      both males (p = 0.001) and females (p = 0.021). The male-to-female ratio widened
      significantly from 0.09:1 to 0.03:1 (p = 0.0001). Further studies are needed to
      determine the incidence and observed changes of different cancers, including
      breast among patients with HIV/AIDS.

PMID- 10918767
TI  - Primary torsion of the greater omentum.
AB  - Primary omental torsion is a rare cause of acute abdominal pain. A case of
      omental torsion in a 49-year-old woman who presented with clinical features
      consistent with acute appendicitis is discussed with a review of the literature.

PMID- 10918768
TI  - Recurrent radial artery aneurysm in a five-month-old infant.
AB  - Distal radial artery aneurysms are an infrequent occurrence in adults and rare in
      children. The rate of aneurysm formation in adults has been reported as 0.048%
      following catheterization. A case report of a 5-month-old girl with a recurrent
      left radial artery aneurysm is presented. The etiology of the aneurysm was radial
      artery catheterization in the neonatal intensive care unit. Recurrence occurred
      after resection for an end-to-end repair. Ligation of the artery was required for
      ultimate treatment. No deleterious sequelae were found after the final operation.

PMID- 10918769
TI  - How to be rational in prescribing antibiotics.

PMID- 10918770
TI  - Lyme disease (borreliosis)--as a possible cause of depression.

PMID- 10918771
TI  - Modernisation of prison healthcare?

PMID- 10918773
TI  - Near-death experiences.

PMID- 10918772
TI  - Public awareness of cigarette smoking and erectile dysfunction.

PMID- 10918774
TI  - Physical, psychological and behavioural manifestations of stress.

PMID- 10918775
TI  - Classification of epilepsy and epileptic seizures.

PMID- 10918776
TI  - Primary care groups--a combination of possibilities?

PMID- 10918777
TI  - Beneficial effect of moderate alcohol consumption on vascular disease: myth or
      reality?
AB  - Moderate ethanol consumption (1-3 drinks/day on 5-6 days/week) has a favourable
      effect on vascular disease-related mortality and morbidity [especially ischaemic
      heart disease (IHD)]. This cardioprotective effect may be due to significant
      effects on cardiovascular risk factors such as high density cholesterol (HDL)
      concentration (HDL protects from IHD) and an inhibition of platelet aggregation
      (increased platelet aggregability predicts coronary events). In contrast,
      alcoholics and problem drinkers have an excess of IHD-related, and possibly
      stroke-related, mortality. Excessive alcohol intake may raise the blood pressure.
      Prolonged alcohol abuse can also result in alcoholic heart muscle disease.
      Alcohol is the major cause of non-ischaemic cardiomyopathy in Western society.
      Although there is a widespread belief that red wine protects more than other
      alcoholic beverages, several studies do not support this interpretation.

PMID- 10918778
TI  - Evaluating the child with proteinuria.
AB  - Proteinuria is a common laboratory finding in children. It might represent a
      benign condition or herald the presence of a serious underlying renal disease or
      systemic disorder. Investigation to confirm a diagnosis or seek reassurance is
      important. This paper discusses the various causes of proteinuria, and those
      aspects of the history, physical examination, and the laboratory tests that will
      help determine the cause or reassure that a serious problem is not currently
      present.

PMID- 10918779
TI  - Menstrual knowledge and practices amongst secondary school girls in Ile Ife,
      Nigeria.
AB  - The menstrual knowledge and practices of 352 randomly selected healthy Nigerian
      schoolgirls were studied. 187 (53.1%) had attained menarche. 40% of subjects were
      deficient in knowledge about menstruation. Although menstrual knowledge was
      higher in post-menarcheal girls, 10% of these were totally ignorant about menses
      and 84% were not psychologically prepared for the first menses. Girls' menstrual
      knowledge was positively associated with parental education. The major source of
      menstrual information was the family. Although more than half of the girls
      menstruated regularly, 66.3%, used insanitary materials as menstrual absorbent.
      The mean duration of menstrual flow was 4.32 +/- 1.15 days (mean +/- SD) with a
      range of 3-7 days in 95.2% of the study population. There is an acute need for
      education and psychological preparation of girls for menstruation well ahead of
      menarche.

PMID- 10918780
TI  - Cognitive-behavioural approaches and weight management: an overview.
AB  - The prevalence of obesity has been on the increase and, on the whole,
      improvements in patient education have not led to the desired outcome of weight
      maintenance--let alone weight loss. For some time therapeutic techniques derived
      from behavioural psychology, such as self-monitoring, stimulus control and goal
      setting, have been incorporated as adjuncts to the treatment of weight problems-
      intended to help obese people make positive changes to their eating and activity
      habits. In more recent decades, behaviour modification approaches have also
      incorporated strategies from cognitive therapy, which have involved the
      identification and modification of 'dysfunctional' thinking patterns and
      consequent negative mood states; hence the term 'cognitive behaviour therapy'
      (CBT). There is increasing interest in adopting CBT approaches to achieve more
      modest and sustainable weight loss and improved psychological well-being. It is
      possible to train non-psychologists to use CBT strategies, though the level of
      training required for effective delivery has not yet been established. While CBT
      is not a panacea for problems of overweight it does offer additional treatment
      choice for some--and is compatible, as an adjunct, with other forms of obesity
      management.

PMID- 10918781
TI  - Epistaxis: a review.
AB  - Epistaxis, being the commonest ear, nose and throat (ENT) emergency requiring
      hospital admission, is clearly an important condition--not only to the specialist
      but also to any general practitioner. This short review looks at the aetiology,
      associated clinical considerations (especially those of hypertension and
      hypoxaemia) and evolution of its management. Herein is also suggested a
      methodical and systematic approach to treating the disorder, both at the level of
      the accident and emergency department and at that of in-patient care. The patient
      with epistaxis of a refractory nature is included, too--along with a selection of
      the options available for treatment.

PMID- 10918782
TI  - Sensory and movement-led approach to design for elderly severely mentally ill
      units.
AB  - The evolution of a design embodying the alliance of movement to sensory stimulus
      for confused and Alzheimer sufferers. The paper is an account of the design
      concept of an Elderly Severely Mentally Ill (ESMI) unit under the Government
      Private Finance Initiative (PFI) rules. Previous papers by the author recorded
      the development of elderly care nursing units that sought to use the planning of
      circulation as a means to provide stimulation for patients. The results
      demonstrated a therapeutic value for this approach. In the latest version for
      ESMI, the concept has been taken further with the creation of a "Memory Trail"
      that provides a choice of routes with organised points of interest containing
      stimulus for the senses in order to trigger memory. This is seen as beneficial
      not only for patient but also provides a positive role for relatives in escorting
      and planning the "journey". The paper records how the design amended the original
      brief by the participation of user groups re-evaluating the requirements in
      discussion and visits to earlier versions of this approach.

PMID- 10918783
TI  - Complementary therapy: complement or threat to modern medicine?
AB  - Some believe that medicine has lost its holistic perspective as a result of which
      many people now seek help from 'alternative' practitioners who seem able to
      devote time to their patients and listen to their concerns. Such practitioners
      also treat the 'whole person' rather than only their symptoms, a feature which
      seems to be valued by patients. The use of complementary therapies is, therefore,
      increasing world-wide. This paper explores this increase, questioning whether
      this truly reflects dissatisfaction with 'traditional' (allopathic) medicine or
      rather represents an increased satisfaction with 'alternative' therapies. It also
      investigates the use of such therapies in mainstream medicine revealing
      considerable variation in attitudes towards and use of such therapies in current
      medical practice questioning whether this should be seen as a threat to modern
      medicine or their use may enhance patient well-being and quality of life.

PMID- 10918784
TI  - Lessons to be learned: a case study approach: ascites and elevated serum CA 125
      due to a pancreatic carcinoma. A diagnostic dilemma.
AB  - A 72 year-old lady with unrecognised cancer of the body of the pancreas presented
      with a 4-month history of progressive loss of weight and ascites. The results of
      laboratory investigations were either negative or within normal limits--apart
      from a raised serum CA 125 level; no tumour mass was detected on diagnostic
      imaging. She underwent exploratory laparotomy for a suspected ovarian tumour, but
      this proved not to be the correct diagnosis. A serum CA 19-9 level was
      subsequently requested and found to be significantly raised; a second contrast CT
      scan then showed the presence of ill-defined peri-aortic tissue. A further
      exploratory laparotomy was carried out in order to establish the true nature of
      the problem; a large pancreatic carcinoma was revealed.

PMID- 10918785
TI  - Botanical perspectives on health: of cystitis and cranberries.
AB  - With generalised increased use of antibiotics there has been the accompanying
      development of antibiotic resistance. It has been suggested that the therapy of
      uncomplicated cystitis is one area in which it is possible to reduce the usage of
      such compounds. Many women have long drunk cranberry juice--and it has become an
      'old-wives' tale in the treatment of this infection. Perhaps it is now time for
      science to investigate further the benefits of the humble cranberry.

PMID- 10918786
TI  - [On the differences in attitude and awareness of clinical doctors, health
      administrators and other health workers to tuberculosis treatment in Japan and
      the US].
AB  - Peculiarity of TB treatment in Japan is a higher rate and duration of
      hospitalization than in other developed countries. Improvement of the TB control
      policy in Japan necessitates reexamination of the issue of treatment policy,
      which requires consideration of recognition and understanding of the concept of
      TB infection, human rights and the protection of patients as well as the society.
      Therefore, this study aims at clarifying and analyzing the differences in TB
      treatment policies in Japan and the US. For the US, a questionnaire was sent to
      TB Directors of states and large cities in order to analyze TB control policies.
      Moreover, the author attended the NTCA meeting held in Chicago to interview 16 TB
      Directors. In Japan, the author sent the same questionnaire translated into
      Japanese to medical doctors in 54 National TB sanatoria. The hospitalization
      rates of new smear-positive TB patients were 100% (median) in Japan and 59% in
      the US. The periods of hospitalization of these patients were 150 days (median)
      in Japan and 10 days in the US. The total expenses of TB diagnosis and treatment
      per capita were approximately US $25,000 and 20,000, respectively in Japan and
      the US. If the DOT strategy were applied to the new smear-positive TB cases in
      Japan, those total expenses would be reduced to half. On the measures against the
      TB patients who pose a threat to the public, the US has the series of TB control
      strategies which contain the reporting system, home isolation, incarceration and
      penalties for violation, while Japan has only the strategy of hospitalization.
      The TB policies of Japan in future would need to focus more selectively and carry
      out thoroughly as seen in the US. The recommended TB policies for Japan obtained
      from this study are to set TB policies adapted to regional characteristics and to
      review the strategy against patients posing a threat to the public.

PMID- 10918787
TI  - [The complication with tuberculosis of the central nervous system in patients
      with miliary tuberculosis].
AB  - The complication with tuberculosis of the central nervous system (CNS) were
      studied in 16 patients with miliary tuberculosis who were admitted to our
      hospital during a period of two years from April, 1997 to March, 1999, and were
      examined by head MRI. Twelve cases (75%) were diagnosed as having tuberculosis of
      CNS. Six cases had tuberculosis of CNS which was found during the screening of
      miliary tuberculosis cases, and all had only cerebral tuberculoma. Meningeal
      irritative symptoms led to the discovery of tuberculosis of CNS in the remaining
      six cases, in which cerebral tuberculoma was complicated with tuberculous
      meningitis. Of these cases of meningitis, three cases showing disturbance of
      consciousness died, but no cases of death was found in cases by the screening.
      The length of time from the onset of symptoms to the diagnosis of tuberculosis
      was long in many of the cases complicated with tuberculosis of CNS compared with
      the cases without such a complication. In the cases of miliary tuberculosis, the
      rate of complication with tuberculosis of CNS is high, and the possibility of
      patients developing serious symptoms suddenly even when they were asymptomatic at
      the time of diagnosis and the paradoxical expansion that becomes intensified
      after initiation of treatment have been reported. Therefore, it is necessary to
      make a close checkup of CNS when the diagnosis of miliary tuberculosis has been
      made.

PMID- 10918788
TI  - [A case of pulmonary tuberculosis complicated with multiple bone and joint
      tuberculosis].
AB  - A 29-year-old male complaining of fever and general fatigue was admitted to our
      hospital. On admission chest X-ray showed infiltrative shadows with cavities in
      the bilateral lung apical areas, and sputum examination for acid fast bacilli was
      smear positive, Gaffky 1. He was treated as pulmonary tuberculosis (TB), and
      chest X-ray findings and sputum examination improved after a few months of
      treatment with antituberculous chemotherapy (INH, RFP, EB, PZA). However,
      tuberculous cold abscess appeared in retropharyngeal area, subcutaneous tissue of
      thoracic cage and retroperitoneal space, and shortly later, bone and joint TB
      were recognized in shoulder and wrist joints and vertebrae. The findings of
      vertebral foci were not recognized by a simple X-ray picture of vertebrae. at
      that time, but MRI of vertebrae showed low intensity areas with ring enhancement
      in the cervical, thoracic and lumbar vertebrae. Despite treatment with
      antituberculous agents, new bone and joint TB had developed in many tissues and
      had accompanied with cold abscess in adjacent tissue, whereas pulmonary TB had
      improved after the initial transient worsening. The appearance of bone and joint
      TB was most probably caused by the initial transient worsening of hidden bone and
      joint TB as a part of the initial systemic transient worsening of tuberculosis.
      After treatment for 4 months, pulmonary TB as well as bone and joints TB had
      improved. Tuberculous cold abscess in retropharyngeal may be secondary to
      cervical vertebral TB but is now rarely seen. In this case, involvement in many
      tissues such as retropharyngeal area, subcutaneous tissue of thoracic cage and
      retroperitoneal space were seen, and these findings are now uncommon and usually
      represents involvement secondary to contiguous infection.

PMID- 10918789
TI  - [Frequency of complication of diabetes mellitus in pulmonary tuberculosis].
AB  - The frequency of complication of diabetes mellitus in patients with pulmonary
      tuberculosis is high, and the presence of diabetes mellitus plays an important
      role in the development of pulmonary tuberculosis. We studied the frequency of
      complication of diabetes mellitus by year, sex and age among patients with
      pulmonary tuberculosis who were discharged from our hospital during a period of
      12 years from 1987 to 1998. The number of diabetic cases in patients with
      pulmonary tuberculosis was 588, namely 14.1% out of 4169 patients during the 12
      years from 1987 to 1998. The frequency of complication of diabetes in every four
      years period showed an increasing trend; 144 cases (11.8%) out of 1225 cases from
      1987 to 1990, 208 cases (14.5%) out of 1434 cases from 1991 to 1994, and 236
      cases (15.6%) out of 1510 cases from 1995 to 1998. By sex, the frequency of
      complication with diabetes mellitus in male was about twice that of female, with
      501 cases (16.0%) out of 3127 cases in male and 87 cases (8.3%) out of 1042 cases
      in female. By age, the frequency of complication of diabetes mellitus showed a
      peak in the 40s and 50s in male, being 21.3% and 23.4% respectively. In female,
      it showed a peak in the 60s, being 18.5%. In conclusion, in the 12 years the
      frequency of complication of diabetes mellitus in tuberculosis cases has been
      increasing, and the presence of diabetes mellitus has been playing more important
      role in the development of pulmonary tuberculosis.

PMID- 10918790
TI  - Printed journals and the Internet: a functional relationship.

PMID- 10918791
TI  - "The good and the bad dying indiscriminately": the Athenian plague reconsidered.

PMID- 10918792
TI  - Sir Jimmy and the worm slayers.

PMID- 10918794
TI  - On dancing and wrestling: reflections on my grandfather's illness.

PMID- 10918793
TI  - Healing with oxygen: a history of hyperbaric medicine.

PMID- 10918795
TI  - On service, off service.

PMID- 10918796
TI  - On the accumulation of small insults.

PMID- 10918797
TI  - Two illnesses.

PMID- 10918798
TI  - Hubris and the well-trained physician.

PMID- 10918799
TI  - Don't hold back your tears.

PMID- 10918800
TI  - First patient.

PMID- 10918801
TI  - [On meta-analysis and QUOROM].

PMID- 10918802
TI  - [Improving the quality of reports of meta-analyses of randomized controlled
      trials: the QUOROM Statement].
AB  - BACKGROUND: The Quality of Reporting of Meta-analyses (QUOROM) Conference was
      convened to address standards for improving the quality of reporting of meta
      analyses of clinical randomised controlled trials (RCTs). METHODS: The QUOROM
      group consists of 30 clinical epidemiologists, clinicians, statisticians,
      editors, and researchers. In conference, the group was asked to identify items
      they thought should be included in a checklist of standards. Whenever possible,
      checklist items were guided by research evidence suggesting that failure to
      adhere to the item proposed could lead to biased results. A modified Delphi
      technique was used in assessing candidate items. RESULTS: The conference resulted
      in the QUOROM statement, a checklist, and a flow diagram. The checklist describes
      our preferred way to present the abstract, introduction, methods, results, and
      discussion sections of a report of a meta-analysis. it is organized into 21
      headings and subheadings regarding searches, selection, validity assessment, data
      abstraction, study characteristics, and quantitative data synthesis, and in the
      results with 'trial flow', study characteristics, and quantitative data
      synthesis; research documentation was identified for eight of the 18 items. The
      flow diagram provides information about both the numbers of RCTs identified,
      included, and excluded and the reasons for exclusion of trials. INTERPRETATION:
      We hope this report will generate further thought about ways to improve the
      quality of reports of meta-analyses of RCTs and that interested readers,
      reviewers, researchers, and editors will use the QUOROM statement and generate
      ideas for its improvement.

PMID- 10918803
TI  - [Change in the drugs administration pattern in the Basque Country Community. The
      1991-1996 trend].
AB  - BACKGROUND: A reduction of intravenous route as a method of consuming drugs and a
      change towards to the use of less morbid routes has taken place in the last years
      in national and international contexts. Our objective was to examine change
      trends in the drugs administration route in the Basque Country Community and to
      explore factors associated with the injected route (IR) use. METHODS: A time
      based series of cross-sectional studies using data provided by the Information
      System on Drug Abuse (SIT) of the Basque Government was used. A total of 12,382
      admissions to treatment produced between the years 1991 to 1996 was analyzed. For
      the analysis of trends linearity test was play and for the estimation of the
      association between explanatory variables and outcome variable logistic
      regression model was carried out. RESULTS: A significative change in the route of
      drugs administration (chi 2 = 621.3; p < 0.001) is evidence, having decreased the
      prevalence of IR use from 83% 1991 to 52.3% in 1996. The adjusted regression
      model (-2LL = 10,766.7) reveals the age of the drugs users as a protective
      variable (OR = 0.94; IC95% = 0.93 to 0.95). On the contrary, being man (OR =
      1.25; IC95% = 1.11 to 1.39), having received previous treatments (OR = 2.63;
      IC95% = 2.38 to 2.90), being heroine the drug that motivates the demand for
      treatment (OR = 9.41; IC95% = 7.24 to 12.2), and the greater number of
      consumption years (OR = 1.14; IC95% = 1.13 to 1.16), are presented as factors
      associated with a greater utilization of the Injected Route. CONCLUSIONS: Even
      though it has been observed a reduction of the use of the injected route over the
      years, a prevalence of the 52.3% in 1996 continues being too high. It is
      discussed the need of persisting in the application of harm reduction and risks
      prevention strategies.

PMID- 10918804
TI  - [Estimate of type I bipolar disorder prevalence (1996-1998)].
AB  - BACKGROUND: Different methodologies have been employed for conducting the few
      studies made on the prevalence of Type I Bipolar Disorders, which makes it
      impossible to know what impact these disorders have had on public health in
      Spain. The prevalence of Type I Bipolar Disorders is calculated by the degree to
      which lithium carbonate is used. METHODS: The prevalence is estimated by
      calculating the daily doses of lithium carbonate prescribed per 100,000
      inhabitants/day (Treatment Group, NO5AN) throughout the 1996-1998 period for each
      one of the provinces in Spain. The data based on the prescriptions written was
      provided by the Pharmaceutical Planning Bureau of the Ministry of Health and
      Consumer Affairs. RESULTS: A prevalence of 70 cases/1,000,000 inhabitants/day for
      the overall population of Spain was estimated. CONCLUSIONS: Lithium carbonate
      usage by provinces and by years affords the possibility of estimating the
      distribution of Type I Bipolar Disorders in Spain. The figures calculated rank
      Spain at a low-average prevalence, although the methodological differences
      prevent it from being possible to draw any final conclusions.

PMID- 10918805
TI  - [Job satisfaction among primary care professional in area 10 Insalud, Madrid].
AB  - BACKGROUND: The implementation of a total quality model requires ascertaining the
      degree of employee job satisfaction. Our aim is to ascertain the overall degree
      of satisfaction and determine its components employed in Primary Care District
      No. 10. METHODS: Descriptive cross-sectional study conducted in Spanish National
      Health Institute Primary Health Care District No. 10 in Madrid. A total of 668
      health care and non health care professionals are employed in this District. A
      Font Rojas satisfaction questionnaire adapted by J. Aranaz was used to gauge the
      degree of job satisfaction on a 1-5 scale (1 being the lowest degree of
      satisfaction and 5 the highest). RESULTS: Eighty percent of the population
      answered the questionnaire. The average satisfaction mark was 3.12 (Standard
      Error SE = 0.017). The aspects ranked the lowest were the stress involved in the
      job, averages 2.30 (SE = 0.041) and professional promotion an average of 2.42 (SE
      = 0.038). The aspect valued most highly was that of professional skill, averaging
      4.01 (SE = 0.058). CONCLUSIONS: These professional are satisfied to an average
      degree with their work. On comparing this study with one conducted in this same
      District in 1992, we have drawn the conclusion that the aspects of work-related
      stress and professional promotion continue to be those ranked the lowest, which
      should lead to corrective measures being taken on the part of the management
      teams.

PMID- 10918806
TI  - [Senior citizen health conditions and hospitalization on geriatric, general and
      surgical floors, a population study conducted in Toledo].
AB  - BACKGROUND: The health condition and some clinical aspects configure a group of
      senior citizens in need of further care who could benefit from specialized
      geriatric care, although no consensus exists as to how to identify these
      patients. The aim of this study is to describe the profile of those patients over
      64 years of age who are hospitalized in a geriatric unit and to compare this
      profile to the senior citizens hospitalized in general medical and surgical
      units. METHOD: A cohort representative of the population over age 64 in the
      Judicial District of Toledo (n = 3214) was studied over an eighteen-month period
      for the purpose of identifying the income and length of stays at the public
      hospitals in the health care district in question. The health condition-related
      variables were gathered by means of personal interviews, and the income and the
      different aspects thereof by way of hospital admissions department data. RESULTS:
      A total of 410 individuals were admitted (12.8%), 168 patients (30.7%) in
      geriatrics, 204 (37.3%) in medical units and 174 (32.0%) in surgical units. In
      geriatrics, the average age was significantly higher (age 77.4), there being no
      differences in the average length of stay (12.8 days; CI 95%) 10.6-14.0), 44
      patients (8.1%) having died, 26 (59.1%) hospitalized in geriatrics. More females,
      younger patients having minor vision and hearing impairments were admitted to the
      surgical units. In geriatrics, as compared to the medical units, more patients
      over 80 years of age, living in senior citizen living facilities, having no
      spouse, moderate-to-severe functional dependence, impaired cognitive function,
      depression, poor quality of life and scanty social resources. CONCLUSIONS: No
      differences were found to exist between the health conditions of those over age
      64 who were hospitalized in non-surgical and surgical units. In geriatrics, as
      compared to the other groups of units, the patients were older, in worse
      condition, had a higher death rate and similar average length of stay.

PMID- 10918807
TI  - [Changes in HIV-related attitudes and knowledge of teenagers following the
      Aulasida intervention in 1996-1997].
AB  - BACKGROUND: Schools being the ideal setting for carrying out Health Education
      activities, the aim of this study was that of pinpointing and quantifying the
      changes in attitudes and knowledge on the part of teenagers enrolled in school in
      Algemesi (Valencia) following an educational intervention regarding HIV
      infection. METHOD: Eleven schools at which a total of 2,599 teenagers (ages 12
      19) were enrolled in eleven different years of study (Secondary Education,
      Secondary Ed. and School Leaving Certificate, College Preparation Course and
      Vocational Training) were invited to take part. The Aulasida intervention carried
      out during the 1996-1997 school year consisted of an informative lecture-panel
      discussion and student involvement activities in small groups using educational
      materials. The gauging instrument was a questionnaire. This questionnaire was
      designed in a before-and-after cross-sectional study. An analysis was made
      divided into age and educational level strata. The averages were compared with
      the Student "t" test and the percentages of change with ji square. RESULTS: A
      total of nine schools accepted taking part. 1575 students answered the "before"
      test (47.4% males and 52.1% females), the average age being 15.2 (1.96) years
      old. The average number of correct answers to the "before" test was 13.5 (2.8).
      The "after" test showed an overall increase of up to 14.7 (3.0) correct answers
      (p < 0.01). By educational levels, this increase was highly appreciable in the
      younger age group. The most common sources of information on HIV were: television
      (80.8%); Aulasida (76.8%), teachers (60.9%), pamphlets (58.4%) and films (53.7%9.
      CONCLUSIONS: Educational interventions are useful tools for increasing knowledge
      and improving attitudes regarding HIV infection. Secondary schools are the best
      environment for this purpose, it being necessary to carry out interventions among
      younger groups, as a greater impact is thus achieved.

PMID- 10918808
TI  - [Knowledge of AIDS of the medical students from three Mexican universities].
AB  - BACKGROUND: The Hegemonic Medical Model is discussed and is articulated with the
      postulates of the sociology of the professions. The information takes Aids as a
      specific topic, because it involves the aspects of recent scientific development,
      of clinical and epidemiological importance and due to the research which is being
      done for its treatment and the production of immunizations. METHOD: This is a
      case study of students enrolled in different years of study for medical degrees
      at the three main universities in Mexico City. A closed-question questionnaire
      was handed out, checked and corrected, the variables of which were related to
      three types of knowledge, that is, basic, technical and general. RESULTS: The
      students were revealed to master this subject to only a minor extent the
      extensions of the knowledge of the disciplines of the profession however being
      applied to new cases without the suitable accuracy. A certain degree of
      dissociation was found to exist among the different types of knowledge which were
      researched, the professional know-how having been noted to clearly conform within
      specialized, segmented, curative logic of the Hegemonic Medical Model.
      CONCLUSIONS: The technical, problem-solving knowledge employed in clinical use
      prevails over the systematic, abstract knowledge of the general knowledge of
      medicine. A clear notion of the processes based on the dominant medical pattern
      is revealed in the single-causal relations of the disease. There is an extension
      of the basic knowledge a the resolving of clinical problems. The medical students
      are oriented toward taking in knowledge which will be useful to them in clinical
      practice.

PMID- 10918809
TI  - [Cardiovascular risk factor prevalence among a smoking population starting
      treatment to quit smoking].
AB  - BACKGROUND: The prevalence of cardiovascular risk factors in the population at
      large is high, nevertheless, this rate is known to a lesser degree for a smoking
      population. The purpose of this study is to ascertain the prevalence of
      cardiovascular risk factors in a cohort of smokers who are starting treatment to
      quit smoking. METHODS: This is a descriptive study conducted on a sample of 1887
      subjects (1098 males and 789 females) within the 20-80 age range. Each one of
      these subjects underwent a medical examination, a blood pressure check, total
      cholesterol, basal gylcemia testing and were measured and weighed. RESULTS: The
      most prevalent factor was high blood pressure (25%). The prevalence of one or
      more risk factors related to cigarette smoking was 36.2% (45.3% among males and
      23.7% among females, the difference being statistically significant, (chi 2 =
      91.4 p < 0.0001). Independently of the number of factors involved, prevalence was
      always greater among the males. With the exception of bdy mass among males, the
      prevalence of the rest of the factors showed a significant increase with age
      among both males and females. Among the males, there was a percentage increase in
      index related to cigarette smoking. To the contrary, the presence of
      hypercholesterolemia decreased along with the increase in the amount of smoking.
      CONCLUSIONS: The prevalence of the cardiovascular risk factors among a smoking
      population starting treatment is major. This fact conditions the need of setting
      up measures for taking action to modify these factors.

PMID- 10918810
TI  - [Genetically modified foods and current epidemiology].

PMID- 10918812
TI  - [Health risks of genetically modified foods: a literature review].
AB  - In 1999, there has been much concern on the safety of genetically modified (GM)
      foods, an important and complex area of safety research, which demands rigorous
      standards. Various groups, including consumers and environmental Non Governmental
      Organizations (NGO) have suggested that all GM foods should be subjected to long
      term animal feeding studies before approval for human consumption. The main goal
      of this review has been to know which is the state-of-the art regarding to the
      potential adverse effects of GM foods. Two databases, MEDLINE and TOXLINE, as
      well as a number of URL from INTERNET were used for references. Although
      commentaries, general news and letters to the Editor have been frequently
      published in reputable journals, papers about experimental studies on the safety
      of GM foods are surprisingly very scant. If data on toxicological assessment of
      GM foods have been obtained, these have not been reported in scientific journals
      and subjected to the scientific judgement.

PMID- 10918811
TI  - [Cholesterolemia control in Spain, 2000. A tool for cardiovascular disease
      prevention. Ministry of Health and Consumption, Spanish Society of Cardiology and
      Spanish Society of Arteriosclerosis].
AB  - The report "Cholesterolemia Control In Spain, 2000. A tool for Cardiovascular
      Disease Prevention" reviews current evidence on cardiovascular prevention and
      therapeutical advances occurred in the last years, in order to help overall risk
      based clinical decision-making. Cardiovascular disease ranks as the first cause
      of death in Spain, accounting for almost 40% of total mortality. During the last
      years age-adjusted cardiovascular death rates have been declining, but the
      absolute number of deaths by coronary heart disease is ascending due mainly to
      the population aging. Coronary heart disease is the first cause of hospital
      consultation due both to the lesser coronary heart disease mortality and to the
      increase in coronary heart disease incidence. The demographic, health and social
      impact of cardiovascular disease is increasing and it is likely to go on in the
      next decades. Appropriate treatment of high blood cholesterol and of other major
      modifiable risk factors is crucial for preventing cardiovascular disease.
      Specific actions to carry out depend on the risk to get ill. Individual risk
      stratification is essential as it determines the follow up periodicity and
      treatment intensity. Priorities of control of cholesterolemia and its consequent
      risk are based on risk stratification. The groups for intervention are ordered in
      a descendent priority hierarchy as follows: 1. Secondary prevention: Patients
      with established coronary heart disease or other atherosclerotic disease. 2.
      Primary prevention: Healthy individuals who are at high risk of developing
      coronary heart disease or other atherosclerotic disease, because of a combination
      of risk factors--including lipids (raised total cholesterol, and LDL-cholesterol,
      low HDL-cholesterol and raised triglycerides), smoking, raised blood pressure,
      raised blood glucose, family history of premature coronary disease--or who have
      severe hypercholesterolaemia, or other forms of dyslipidaemia, hypertension or
      diabetes. 3. Close relatives of patients with early onset coronary heart disease
      or other atherosclerotic disease. 4. Others individuals met in connection with
      ordinary clinical practice. In primary prevention, the therapeutic objective in
      high risk patients (risk (3)20%--upon the risk chart of the European Societies of
      Cardiology, Atherosclerosis, Hypertension--or individuals with 2 or more risk
      factors--National Cholesterol Education Program II-) is set up at LDL-cholesterol
      < 130 mg/dl. In secondary prevention, the drug treatment will be indicated when
      LDL-cholesterol (3)130 mg/dl and the therapeutic objective will be LDL
      cholesterol < 100 mg/dl. Statins are first line drugs for treatment of high blood
      cholesterol. Where moderate-severe hypertrigliceridemia or low HDL-cholesterol
      fibrates are preferred. In acute coronary syndrome hypolipemiant treatment, where
      indicated, should be used as soon as possible. Coronary heart disease patients
      should be offered secondary prevention programmes which provide, in a continuous
      manner, a good clinical and risk factor control, with appropriate cost
      effectiveness drugs.

PMID- 10918813
TI  - [Characteristics of those individuals requesting to be seen by a physician
      without first having made an appointment ahead of time].
AB  - BACKGROUND: Waiting time to see a physician is considered to be an indicator of
      user satisfaction. Non-emergency visits made without an appointment ahead of time
      result in longer waiting times for the patients who have appointments, resulting
      in the consequent in satisfaction thereof. The purpose of this study is aimed at
      conducting a quantitative assessment of this type of visits and at ascertaining
      the characteristics thereof for the purpose of putting measures into practice for
      the correction and rationalization thereof. METHODS: Descriptive study. A record
      was made which would gather the characteristics of those patients seeing
      physicians without having made an appointment, such as age, gender and the
      characteristics related to the visit (reason, modality, working hours and whether
      made directly or indirectly). RESULTS: No appointment had been made ahead of time
      for 14.19% of all non-emergency patient-requested visits. Based on the factorial
      analysis of multiple correlations, two visit profiles are identified, that is,
      the direct visits requested by young patients due to illness or red tape at the
      end of the physician's morning hours, said young patients being present, and the
      indirect visits during the visits for which appointments have been made ahead of
      time by patients requesting prescriptions. CONCLUSIONS: There are a large number
      of visits for which no appointment has been made ahead of time. Measures must be
      taken for the purpose of channeling the use of the appointment organization
      system and of improving those situations involving a lack of accessibility for
      the end purpose of improving the degree of satisfaction of those using the public
      health care services.

PMID- 10918814
TI  - [Quality perceived by two populations assigned to two health care centers in the
      province of Cuenca].
AB  - BACKGROUND: To render quality service, it is essential to know the opinion users
      have of the service in question. The purpose of this study is that of gauging and
      comparing the quality perceived by two populations assigned to two health care
      centers in the province of Cuenca. METHOD: This is a descriptive cross-sectional
      study. The Basic Health Care Districts studied were the Cardenete Health Care
      Center and the Motilla del Palancar Health Care Center, both within the Cuenca
      Health Care District. The source of information was personal health care card. A
      random sampling layered by age and gender percentages was taken. The perceived
      quality was gauged by means of a validated, reliable questionnaire used
      previously for similar purposes by the Ministry of Health and Consumer Affairs.
      RESULTS: A total of 295 surveys (147 males and 148 females) were analyzed. The
      average age was age 48.83 (SD: 18.77) for the Motilla Health Care Center and age
      61.93 (SD: 15.17) for the Cardenete Health Care Center. The average monthly
      frequency of visits for the MP Health Care Center was 1.56 (SD: 1.91), this
      average having been 2.49 (SD: 4.27) for the Cardenete Health Care Center. The
      average weekly frequencies for the MP Health Care Center was 0.32 (SD: 0.66),
      having been 0.49 (SD: 1.03) for the Cardenete Health Care Center. The waiting
      time at the MP Health Care Center was 10.86 minutes (SD: 8.27), having been 7.88
      (SD: 4.55) at the Cardenete Health Care Center. 83.4% of the users of the two
      Health Centers of are aware of the fact that they have the freedom to choose
      their primary care physician. CONCLUSION: Statistically significant differences
      were found in 11 of the 21 items studied regarding perceived quality of the which
      questionnaire is comprised. The results of the health care components according
      to the factorial analysis of the items of perceived quality are those coinciding
      with the perceived quality results. Of the two groups of users surveyed, those
      perceiving a higher degree of quality in the health care service they are
      rendered are those of the Cardenete Health Care Center.

PMID- 10918815
TI  - [Personal care habits of individuals over age 65 having no cognitive impairment
      and residing in the Guadalajara Health Care District].
AB  - BACKGROUND: The aim of this study is that of ascertaining the characteristics of
      the personal care habits of those individuals over age 65 who have no cognitive
      impairment within the province of Guadalajara who are residents of the community
      based on the hypotheses that the same are deficient and therefore subject to
      improvement. METHODS: This is an observational, analytical cross-sectional study
      within a Primary Care, distinguishing between the urban and rural environments. A
      questionnaire (involving prior trial and reliability study by means of an
      analysis of the stability of the answers based on a kappa factor) was given out
      to a random, layered ample divided into different stages and proportional by age,
      gender and centers of population. An analysis was conducted of the following
      variables: A) Personal care habits. A. Personal care--daily washing/dressing:
      procedure and frequency, Hair Care, Always washing hands before eating and after
      going to the bathroom; Shaving for men, Oral hygiene. b. Sleep routine. B)
      Sociodemographic variables. The data was analyzed using proprietary descriptive,
      analytical and multivariable logistic regression procedures. RESULTS: The losses
      fell within the 16%-26% range (refusal was found to be the leading cause in the
      rural environmental and non-location in the urban environment). The sample
      finally studied included 388 individuals in the rural environment and 392
      individuals in the urban environment. Half showered and washed their hair at
      least once a week. As high as 15% doe not wash always wash their hands before
      eating and as high as 44% do not do so after going to the bathroom. Over 50% of
      the males shave using the correct procedure. A high percentage of those missing
      part of their teeth as well as those completely toothless do not use dentures,
      and those who do are lacking in hygiene. Sleep routines shows better results.
      CONCLUSIONS: Personal care habits among senior citizens in our province are
      patently subject to improvement in all of the aspects analyzed, especially in the
      rural environment and among males. This should be a priority task under the
      charge of anyone assigned to the Primary Care Teams.

PMID- 10918816
TI  - [Assessment of the effectiveness of health training courses offered for food
      handlers in a health care district of Gandia, Valencia].
AB  - BACKGROUND: Food poisoning is a major Health Care issue. Health training is one
      of the mechanisms available for preventing these illnesses. The purpose of this
      study is that of ascertaining whether food handlers improve their knowledge
      regarding food handling practices by attending the courses which are offered for
      being awarded the handler card and of analyzing the impact of sociodemographic
      variables on the degree of knowledge prior to taking the course. METHOD: Pre-Post
      type assessment study on a sample of 500 handlers who came to the Public Health
      Center in the town of Gandfa (Valencia) to take a training course in October 1997
      February 1998. A self-test questionnaire taken prior to and following the course
      to gauge knowledge and other variables was used. RESULTS: A significant
      difference was found between the pre-test and the post-test, except with regard
      to the subject of personal hygiene. Those handlers having worked at this
      occupation for a longer number of years or who had prior health training answered
      correctly more often. CONCLUSIONS: The training courses heighten the degree of
      knowledge regarding food-handling practices. In training courses, greater
      emphasis must be placed on the subjects of food preservation, preparation and
      serving than on those of personal hygiene or facility cleanliness. Nonetheless,
      it would be of interest to research whether any changes in attitudes occur as an
      initial approach to assessing the effectiveness of the training and ascertaining
      whether any intention exists of putting the knowledge acquired into practice.

PMID- 10918817
TI  - [Biological function of chondroitin sulfate and sulfotransferases].

PMID- 10918818
TI  - [The SREBP pathway: controlling lipid metabolism by two-step proteolysis of a
      membrane-bound transcription factor].

PMID- 10918819
TI  - [Biosynthetic regulation of leukocyte cell surface carbohydrate structures during
      cell differentiation].

PMID- 10918820
TI  - [2-molecular neurobiology of orexins].

PMID- 10918821
TI  - [Constitutive activation of the ERK-MAP kinase pathway in human tumors].

PMID- 10918822
TI  - [Regulating factors for microglial activation].

PMID- 10918824
TI  - [Stable angina pectoris].

PMID- 10918823
TI  - [Rho family small G proteins antagonizing RhoA].

PMID- 10918825
TI  - [Invasive treatment of angina pectoris. A need for re-thinking?].
AB  - Evaluation and treatment of stable angina pectoris is based on invasive
      diagnostic and therapeutic procedures focused on identification and treatment of
      coronary artery stenoses, instead of myocardial ischaemia which is considered the
      cause of symptoms. Thus, coronary angiography should possibly be preceded
      routinely by myocardial perfusion imaging, which can provide the diagnosis of
      ischaemia and determine if the patient will benefit from invasive therapy. As a
      consequence, treatment of patients without ischaemia and patients with ischaemia
      so serious that invasive therapy is futile might be avoided. It is unknown
      exactly how many angiographies and treatments with angioplasty or bypass surgery
      that could be spared in this way. It is estimated that a patient pathway based on
      the diagnosis of myocardial ischaemia including the type of ischaemia may render
      approximately half of the present angiographies and a number of invasive
      revascularisations redundant. This pathway implies substantial economic savings.

PMID- 10918826
TI  - [Thirty years of coronary revascularization in stable angina pectoris. Results of
      randomized controlled trials].
AB  - From a survey of randomized studies we wanted to elucidate the therapeutic gain
      and the risk of complications with coronary artery bypass grafting (CABG) and
      percutaneous transluminal angioplasty (PTCA) in stable angina pectoris. The
      following main conclusions emerged: Invasive revascularization was associated
      with increased survival (reduced frequency of cardiac death or myocardial
      infarction) exclusively in patients with three-vessel disease and/or left main
      lesion accompanied by a decreased left ventricular function. This group accounted
      for less than 10% of treated patients. With regard to survival, patients with one
      and two-vessel disease were better off with conservative treatment. Relief of
      angina was achieved for a number of years in the majority of patients. Angina
      recurred earlier following PTCA than CABG. PTCA is considered less traumatic, but
      a ten times higher need of additional revascularization seems to eliminate this
      advantage. The frequency of serious complications (including the higher risk at
      re-revascularization) was > or = 10% after PTCA and > or = 7% after CABG.

PMID- 10918827
TI  - [Treatment and rehabilitation in an apoplexy unit increases the 5-year survival].
AB  - Treatment of stroke patients in specialised stroke units has become more
      frequent, but the longterm effect of this treatment has not been determined. In
      this prospective, community-based study of 1241 unselected acute stroke patients
      we compared outcome between patients geographically randomised to treatment in a
      stroke unit or in a general neurological/medical ward, from the time of acute
      admission to the end of rehabilitation. Baseline characteristics were comparable
      between the two treatment groups regarding age, sex, marital status, pre-stroke
      residence, and stroke severity. Patients treated in the stroke unit had higher
      comorbidity with regard to hypertension and diabetes. Multivariate linear and
      logistic regression analyses were applied to estimate the independent influence
      of stroke unit treatment on outcome. Stroke unit treatment significantly reduced
      not only initial mortality, but also mortality within five years from stroke
      onset. The relative risk of dying within the first five years from stroke was
      reduced by 40%, p < 0.01. Treatment and rehabilitation of unselected stroke
      patients in a stroke unit reduces initial mortality, discharge rate to nursing
      home, reduces cost of treatment, and improves longterm survival up to five years
      after stroke.

PMID- 10918828
TI  - [Infantile hypertrophic pyloric stenosis. Decreasing incidence].
AB  - The aim of this study was to confirm a clinical suspicion that the frequency of
      this disease is in decline. A retrospective review of case notes of all children
      admitted and operated in all hospitals in Viborg County during the period of
      1.1.1973 to 31.12.1997 was performed. The local survey was supplemented with a
      national survey. One hundred and forty-seven patients from Viborg County were
      operated for infantile hypertrophic pyloric stenosis during the period described.
      Divided into five year periods the number per 1000 living births was
      consecutively 1.6, 2.4, 2.0, 2.8 and 0.9. The same tendency was found nationally,
      Table 1. The decrease started in 1993 and has since strengthened. The reason is
      unknown, but there is a relation regarding to the timing of a change in
      recommendations concerning positioning of infants during sleep. However, a causal
      relation is unknown.

PMID- 10918829
TI  - [Infantile hypertrophic pyloric stenosis. A 25-year study from the county of
      Viborg].
AB  - In order to investigate an apparent decline in the incidence of infantile
      hypertrophic pyloric stenosis (IHPS), all cases of IHPS from 1973-1997 in the
      county of Viborg were studied retrospectively. One hundred and fourty-seven
      patients were found, with a significant decrease in incidence in the last five
      year period. Ninety-two percent were males, 14% had a family history of IHPS.
      Eleven percent had a birthweight < 2500 g, as opposed to 5-6% in the normal
      population. Pyloric stenosis presents in one to four weeks after birth in 70% and
      in 5-12 weeks in 28%. The diagnosis was reached solely through the the clinical
      picture in 105 cases. Twenty-three were examined with upper gastrointestinal
      radiography, six were false negative, abdominal ultrasound was performed in 21
      cases and was false negative in four. Five patients were reoperated because of an
      inadequate first operation. Postoperative complications with wound infections
      were seen in eight patients. A high degree of accuracy of diagnosis can only be
      achieved through the clinical picture.

PMID- 10918830
TI  - [Drug prescriptions for Danish children].
AB  - We used a prescription database to identify all reimbursed prescriptions for
      children aged 0-15 years living in North Jutland County (population 95,134),
      Denmark, during 1997. We identified 154,189 prescriptions for 48,091 child users.
      The mean prescription rate was 1621/1000 children/year. Overall, half of the
      child population purchased > or = 1 prescription. In children younger than three
      years, 75.3% purchased prescriptions, and 17.5% received > or = 5 prescriptions.
      Systemic antibiotics, anti-asthmatics, ophthalmologicals, and dermatological
      corticosteroids accounted for 82% of the prescriptions. One-third of the 0-2 year
      old children purchased prescriptions for anti-asthmatics, mainly systemic beta 2
      agonists, and almost half purchased antibiotics, mainly broad-spectrum
      penicillins. In the 7-15 year olds, 39.1% redeemed at least one prescription. The
      study stresses the need for epidemiological studies on the reasons for drug use
      and evaluation of pharmacological effects in children.

PMID- 10918831
TI  - [Transnasal gastroscopy].
AB  - The use of transnasal endoscopy has not been reported earlier in Denmark. This
      study describes the preliminary experiences with transnasal gastroscopy using the
      Olympus XGIF-N200 prototype. Patients scheduled for diagnostic gastroscopy were
      examined transnasally. The patients answered questions regarding anxiety and
      discomfort, and the endoscopist commented on the quality of the procedure. Of
      sixty patients included, 56 (93%) were examined transnasally. Two patients did
      not have nasal passage and were examined orally, and two patients were examined
      with standard gastroscope because of technical difficulties. Sixty-eight percent
      of the procedures were unsedated, 55% of the patients did not experience gag
      reflexes. The procedure was described by most patients as "slightly
      uncomfortable". Twenty-five percent had uncomplicated epistaxis. Pulse rate and
      saturation levels were stable. Transnasal gastroscopy seems to be well tolerated
      by the patients, as both subjective and objective criteria were better than those
      for conventional gastroscopy.

PMID- 10918832
TI  - ["B-Lynch suture" in uterine atony].
AB  - Postpartum haemorrhage is a serious obstetric problem. Two to five percent of
      deliveries may lead to postpartum haemorrhage with a blood loss > 1000 ml within
      the first 24 hours. One of the causes is uterine atony. One case of postpartum
      atony with excess bleeding is presented. The B-Lynch surgical technique was used
      for control of the haemorrhage without any side effects. The technique is
      surgically easy, and effective. It is advisable to use before other surgical
      procedures are effectuated.

PMID- 10918833
TI  - [Should we still accept introduction of new, not-evaluated surgical
      interventions? Can a new procedure be evaluated by controlled trials? Examples
      from urinary incontinence surgery].

PMID- 10918834
TI  - [Increased occurrence of gonorrhea in Copenhagen].

PMID- 10918835
TI  - [Quality development of care and treatment of patients with schizophrenia].

PMID- 10918836
TI  - [Centralization requires documentation, too].

PMID- 10918837
TI  - [Non-invasive coronary arteriography in magnetic resonance scanning].

PMID- 10918838
TI  - [Central and regional hemodynamics of eye in different course of primary open
      angle glaucoma with normalized intraocular pressure and their relationship with
      circulation types, sympathoadrenal activity and hydrocortisone level].
AB  - The relationship of systemic and local hemodynamics with neurohumoral factors has
      been evaluated in 104 patients with primary open-angle glaucoma with normalized
      intraocular pressure. Changes in the functional activity of the sympathoadrenal
      activity and hydrocortisone levels were in high correlation with the initial type
      of systemic hemodynamics: the hormonal activity of the sympathoadrenal system
      predominated in patients with eukinetic and hyperkinetic circulation with normal
      levels of hydrocortisone, while in patients with hypokinetic circulation the
      mediator (norepinephrine) component of the sympathoadrenal system combined with a
      high plasma level of hydrocortisone predominated. A principal characteristic of
      unstable primary open-angle glaucoma, discriminating it from the stable condition
      in all types of circulation, is the presence of deep autonomic disorders in the
      neurohumoral mechanisms of autoregulation of ocular blood flow, because of
      excessive accumulation of norepinephrine, epinephrine, and hydrocortisone in the
      lacrimal fluid at the expense of their decreased utilization by the receptor
      systems of ocular tissues and blood vessels.

PMID- 10918839
TI  - [Comparative assessment of hemodynamic risk factors of glaucomatous optic
      neuropathy progress].
AB  - Comparative evaluation of the significance of hemodynamic factors of risk of
      progress of glaucomatous optic neuropathy has been carried out: blood flow
      velocity, blood flow resistance, blood pressure in the orbital artery-central
      retinal artery system, perfusion ocular pressure in connection with stabilization
      of glaucomatous process, and intraocular pressure were analyzed for a period of
      up to 16 years. The most significant factors were blood pressure in the orbital
      artery-central retinal artery system and perfusion ocular pressure, but not blood
      flow velocity. The leading factor indicating the risk of progress of optic
      neuropathy in primary glaucoma is ocular perfusion pressure. Measurements of
      opthalmodynamometric pressure can be used for evaluation of perfusion pressure
      and recommended for wide clinical application for predicting the course of
      primary glaucoma.

PMID- 10918840
TI  - [Applications of lecozyme with necrolytic purpose for subsequent keratoplasty in
      the treatment of eye burns: an experimental study].
AB  - Necrolytic properties of lecozyme diluted with urea were studied on a model of
      isolated alkaline burn of the cornea with 10% NaOH applied for 10 sec.
      Experimental studies were carried out on both eyes of 62 rabbits (124 eyes).
      Lecozyme applications in a dose of 17.5 FIP dissolved in urea in concentrations
      of 3.5 to 40% brought about a complete necrolytic effect in all cases. The
      results of keratoplasty depended on the concentration of urea. High
      concentrations (10-40%) caused severe complications in the eye (endophthalmitis).
      Application of 5-10% urea solutions caused no complications, but the graft
      healing was opaque in all cases. Satisfactory results were attained with 3.5 and
      4% urea. Postoperative course and outcomes of keratoplasty after pretreatment
      with lecozyme were better than in the control animals subjected to surgical
      necrectomy. We explain better results of surgical treatment of induced burns by a
      higher quality of necrectomy, which can be attained by the enzyme. No melting or
      perforation of the cornea due to the enzyme was observed in any case. Good
      results of experiments necessitate further experimental and clinical studies.

PMID- 10918841
TI  - [Eximer laser correction of complex myopic astigmatism by centered and decentered
      keratoablation].
AB  - Reviews the results of correction of complex myopic astigmatism with asymmetric
      form of disposition on the cornea by two methods, with centered and decentered
      photokeratoablation. Analyzes the results of 80 laser keratomileusis operations
      for medium and high myopia. Describes a method of calculations and
      keratotopographic detection of asymmetric astigmatism and a method for
      transferring it into symmetrical form in computer-aided keratotopography. Two
      types of interventions brought about a good refraction result (sphere equivalent 
      0.66 +/- 0.54 diopters) and high resolving capacity of the eye (0.88-0.99).
      Decentered keratoablation led to a significant increase in visual acuity without
      correction, this indicating a better adequacy of this method, discussed in this
      paper.

PMID- 10918842
TI  - [Quantitative evaluation of ultrasonic images in differential diagnosis of bulky
      intraocular formations].
AB  - A method for evaluating ultrasonic gray-scale images by plotting amplitude
      histograms is proposed. From amplitude histogram analysis, echogenicity and
      homogeneity indexes of the examined tissues were estimated. A total of 213 images
      of bulky intraocular formations in 58 patients were analyzed by this method.
      Confidence intervals of the image echogenecity and homogeneity of choroidal
      melanomas did not overlap the confidence intervals of the above indexes of images
      of pseudotumorous intraocular formations. This permits using the homogeneity and
      echogenicity indexes as a test for differential diagnosis of bulky intraocular
      formations.

PMID- 10918843
TI  - [Role of metabolic vitreous alkalosis and redox processes in pathogenesis of
      senile macular degeneration].
AB  - Studies of acid-base balance (pH-metry) of the vitreous in 32 patients with
      senile macular degenerations and theoretical studies showed an important role of
      redox processes in the pathogenesis of senile macular degeneration, namely,
      intensification of free-radical oxidation, leading to metabolic alkalosis of the
      vitreous.

PMID- 10918844
TI  - [Method for assessing involution ophthalmoendotoxicosis by fluorescent analysis
      of lacrimal fluid].
AB  - A method for evaluating the binding capacity of aqueous humor albumin as
      endoophthalmotoxicosis indicator is proposed, consisting in evaluation of this
      parameter in the lacrimal fluid by fluorescent probe K-35. A correlation between
      the studied parameter in aqueous humor, lacrimal fluid, and blood serum has been
      detected. Albumin binding capacity in the above biological fluids of patients
      with involution ophthalmopathy was low.

PMID- 10918845
TI  - [Course of acute traumatic uveitis and rate of secondary immunological
      insufficiency detection at pre-laboratory level].
AB  - Course of acute traumatic uveitis was evaluated in 146 patients with penetrating
      wounds of different severity in scores starting from the first days after the
      injury was inflicted and after operations performed in early terms after the
      injury. The inflammatory process normalized by weeks 2-3 in a favorable course,
      while in severe injuries and early reoperations and in wounds of the fourth
      degree of severity posttraumatic uveitis persisted during weeks 3-4, and 35.2%
      patients developed chronic posttraumatic uveitis. Clinical signs of immunological
      insufficiency, presenting mainly as the infectious syndrome (28%), were detected
      in 35.6% patients with penetrating injuries on the basis of case history analysis
      by means of a universal diagnostic chart and clinical findings. Penetrating
      wounds of the third and fourth degree of severity, reoperations during early
      terms after primary surgical treatment, chronic inflammatory diseases (mainly of
      the ENT and bronchopulmonary system, indicating secondary immunodeficiency, which
      necessitate prescription of immunocorrectors starting from the first days after
      the injury) are factors of risk of protracted or chronic course of posttraumatic
      uveitis.

PMID- 10918846
TI  - [Immunological status and its changes in children during surgery on anterior eye
      segment].
AB  - Nonspecific and specific immunity values were studied in 70 children before and
      in various periods after 74 operations on the anterior segment of the eyeball. In
      children with persistent autosensitization to ocular tissue autoantigens (alpha
      crystalline and S-antigen) postoperative uveitis presented as an immunocomplex
      disease with signs of exhaustion of the functional potential of the phagocytosis
      and complement systems. In children without autosensitization uveitis was
      associated with immunity activation. Phagocytosis system and cooperation of
      lymphocyte subpopulations, including normal killers (CD16+), play an important
      role in prevention of sensitization to ocular tissue autoantigens. Therefore,
      complex immunological examinations of children before surgery and regular check
      ups after it will help differentiate immunodeficiency from compensatory
      immunosuppression preventing autoimmune disease, which is important in
      prescription of immunostimulating therapy.

PMID- 10918847
TI  - [Clinical features of HLA-B27 positive and negative uveitis].
AB  - A total of 147 patients with uveitis concomitant with spondyloarthritis were
      examined. HLA-B27 histocompatibility antigen was detected in 75.5% patients. Men,
      mainly young and middle-aged, suffering from sacroileitis, developed the disease
      2.5 times more often. Involvement of the uveal tract manifested by acute anterior
      fibrinous plastic uveitis (83.7%), rarely by anterior serous uveitis (16.3%).
      Bilateral uveitis occurred in 46.8% patients. HLA-B27-associated uveitis was
      characterized by a frequently relapsing course. On the other hand, fundus oculi
      abnormalities were detected in 12.6% patients with anterior uveitis; this
      abnormality occurs 4 times more often in subjects with negative HLA-B27 antigen,
      peripheral uveitis occurring 7 times more often. Complications were observed in
      29.5% patients, their frequency and severity did not depend on the presence of
      HLA-B27 antigen.

PMID- 10918848
TI  - [Immunopathogenetic, clinical features and treatment of external exudative Coats'
      retinitis].
AB  - The findings of comprehensive clinical and immunopathogenetic examinations of 42
      patients with external exudative Coats' retinitis showed the significance of
      infection in the etiopathogenesis of disease and helped identify the etiology,
      mainly infectious, in 47.6% patients, which correlated with case histories
      indicating foci of chronic infection and type I immunological insufficiency.
      Toxoplasma infection was the predominant etiological factor (38 cases). The
      predominant clinical symptoms were solid exudation, vascular changes,
      hemorrhages, vitreous involvement, and exudative detachment of the retina.
      Changes in the immune status were as follows: shifts in T- and B-immunity,
      impaired complex formation, in some cases selected deficit of IgA. Association of
      Coats' retinitis with erythrocytic phenotype B(III) was detected in 44% patients
      (p < 0.02); carriers of this blood group are at a high risk (RR 11.16) of the
      disease. The treatment was carried out with consideration for etiology,
      immunopathogenesis, and clinical picture and was supplemented by argon laser
      coagulation, if indicated.

PMID- 10918850
TI  - [Therapeutic algorithms in infectious ulcers of cornea].
AB  - Based on the experience gained at Department of Infections and Allergic Diseases
      of the Eyes and recent publications, the author proposes protocols of drug
      therapy of the major infectious ulcerative diseases of the cornea: herpetic
      ulcer, ulcer caused by Pseudomonas aeruginosa, gonococci, staphylococci, fungi,
      and acanthamedian keratitis. The authors emphasizes that the treatment of ulcers
      of the cornea should be complex, including specific therapy (corresponding to the
      identified agent or the agent most probable as judged from the clinical picture)
      and pathogenetic therapy (metabolic, antiallergic, antiinflammatory,
      immunomodulating, hypotensive). If corneal ulcer is rapidly recognized and forced
      therapy started, good results can be attained even in such a fulminant infection
      as those caused by Pseudomonas aeruginosa or gonococci. On the other hand,
      therapy of keratomycosis and acanthamebian keratitis remains a problem.

PMID- 10918849
TI  - [Antibodies to types II and IV collagens, tumor necrosis factor-alpha and
      circulating immune complexes in lacrimal fluid and serum of patients with
      diabetic retinopathy and different stages].
AB  - Clinical and immunological examinations are carried out in patients with
      preclinical, nonproliferative, preproliferative, and proliferative diabetic
      retinopathy (DR). On the whole, DR is characterized by a notable increase in
      antibody-dependent immune response, associated with appearance of antibodies to
      collagen of the II and IV types in the lacrimal fluid and serum, with the "local"
      reactions predominating. The level of reactions of cellular autoimmune response
      (tumor necrosis factor-alpha) and cell-to-cell reactions in the lacrimal fluid
      and serum is low. Increased level of circulating immune complexes in the serum
      and almost complete absence of free antibodies to collagen in the blood may be
      indicative of formation of pathogenic immune complexes precipitating on vascular
      walls and in other tissues. Various forms of immune response were revealed,
      conducive to a favorable or unfavorable course of DR.

PMID- 10918851
TI  - [Clinical course of isolated larval infestation of orbit in children].
AB  - Clinical course of an isolated infestation of orbital tissues by larvae of
      helminths parasitizing in dogs (Toxocara canis) has been followed up in 5
      patients aged 6-13 years. The process ran a wave-like course for 3-8 months and
      was characterized by cyclic inflammatory changes in the orbit, presenting by
      toxic allergic tenonitis, regional lymphadenitis, optic nerve perineuritis with
      formation of parasitic granuloma detected by computer-aided rhoentgenotomography
      of the orbit. No clinical or laboratory signs of common inflammatory and allergic
      reaction in the presence of Toxocara antigen sensitization were observed in any
      case, which was confirmed by detection of specific antibodies (IgG and IgE).
      Specific therapy with anti-nematode drug albendazol was effective.

PMID- 10918852
TI  - [On the Kraup-Posner-Schlossmann syndrome].
AB  - Five patients with the Kraup-Posner-Schlossmann syndrome are described. The
      disease has been erroneously taken for chronic serous iridocyclitis of
      tuberculous origin with hypertension. One patients later developed a true
      glaucomatous process. The authors believe that the complex of characteristic
      symptoms of glaucomatous crisis in general can be considered pathognomonic for
      this disease. No differential diagnosis for ruling out tuberculous or other
      (endogenous) iridocyclitis is needed in cases when this complex is present.
      Patients with symptomatic ophthalmic hypertension are in need of regular check
      ups.

PMID- 10918853
TI  - [Multiple modality treatment of patients with senile central chorioretinal
      dystrophy with use of electromagnetic field].
AB  - Fifty-one elderly patients with maculodystrophy were observed and treated.
      Exposure to electric field of 1-2 mV/cm and 40-57 Hz led to improvement of
      microcirculation in the fundus oculi and decreased vision disorders.

PMID- 10918854
TI  - [Seven cases with angioid retinal strips].
AB  - Seven patients with angioid strips of the retina are described. In 5 patients
      angioid strips were concomitant with Darier's elastic pseudoxanthoma. In 3 the
      disease was hereditary (2 sisters and a daughter of one of them). In 2 patients
      chorioretinitis of tuberculous and obscure etiology was diagnosed before they
      were admitted into clinic. The process stubbornly progressed. Conservative
      therapy and laser coagulation were ineffective in the majority of cases or gave
      but a short alleviation.

PMID- 10918855
TI  - [Atypical variant of central retinal vein branching].

PMID- 10918857
TI  - Gas Hydrates: Challenges for the Future. Proceedings of the 3rd International
      Conference on Gas Hydrates. Salt Lake City, Utah, USA. July 18-22, 1999.

PMID- 10918856
TI  - [Use of collalysine in ophthalmology].

PMID- 10918858
TI  - Serving underserved communities.

PMID- 10918859
TI  - The effect of snoring and obstructive sleep apnea on the sleep quality of bed
      partners.
AB  - OBJECTIVE: To measure the effect of snoring and obstructive sleep apnea (OSA) on
      the sleep of snorers' bed partners and to determine whether a bed partner's sleep
      improves when snoring and OSA are treated. MATERIALS AND METHODS: We studied 10
      married couples in which 1 member was undergoing polysomnography to evaluate
      suspected OSA. The patients and their spouses underwent simultaneous
      polysomnography. Midway through the 1-night study, the patients received nasal
      continuous positive airway pressure (CPAP) with the pressure adjusted to
      eliminate snoring and obstructive breathing events. Apnea-hypopnea index
      (episodes/hours of sleep time), arousal index (arousals/hours of sleep time), and
      sleep efficiency (percent time asleep) were calculated to measure sleep quality.
      RESULTS: The patients (all male) demonstrated a median (range) apnea-hypopnea
      index of 26 (3-75) that decreased to 7 (0-34) during the trial of nasal CPAP
      therapy (P < .05). During the CPAP trial, the median (range) arousal index of the
      spouses decreased from 21 (14-34) to 12 (4-27) (P < .01), and the spouses' median
      (range) sleep efficiency increased from 74% (56%-80%) to 87% (64%-95%) (P < .01).
      CONCLUSION: The elimination of snoring and OSA in these patients was associated
      with an improvement in the quality of their bed partners' sleep, as indicated by
      improved sleep efficiency and continuity, even when the spouses had been
      habitually exposed to snoring and OSA. Assuming that 480 minutes were spent in
      bed for sleep, a 13% improvement in sleep efficiency (i.e., from 74% to 87%)
      translates to an additional 62 minutes of sleep per night for the spouses of
      snorers with OSA.

PMID- 10918860
TI  - Effects of cardiac rehabilitation and exercise training programs on coronary
      patients with high levels of hostility.
AB  - OBJECTIVE: To determine the effects of cardiac rehabilitation interventions on
      patients with hostility, or unexpressed anger, a coronary heart disease risk
      factor that adversely affects morbidity and mortality after major coronary heart
      disease events. METHODS: Using validated questionnaires to evaluate behavioral
      characteristics and quality of life, we studied 500 consecutive patients before
      and after cardiac rehabilitation and compared a group of 65 patients with high
      levels of hostility with 435 patients with low levels of hostility. RESULTS:
      After rehabilitation, statistically significant improvements occurred in the
      total cohort in scores for anxiety, depression, and somatization, as well as
      total quality of life, but not in hostility score (-20%; P = .07). Patients with
      high levels of hostility had significant improvements in hostility scores as well
      as other behavioral characteristics (anxiety, depression, and somatization) and
      all quality-of-life components. These patients also improved exercise capacity,
      percent body fat, body mass index, and total cholesterol and high-density
      lipoprotein cholesterol levels. Compared with patients with low levels of
      hostility, those with high levels of hostility had greater relative improvements
      in hostility scores, as well as anxiety, general health, energy, mental health,
      and total quality-of-life scores, and had similar improvements in exercise
      capacity, obesity indexes, lipid levels, and other behavioral characteristics and
      quality-of-life measurements. After cardiac rehabilitation, the prevalence of
      high levels of hostility decreased by 40%, from 13% to 8% (P < .01). CONCLUSIONS:
      These data suggest that cardiac rehabilitation reduces hostility and
      significantly improves quality of life and other behavioral characteristics in
      patients with high levels of hostility. We believe that greater attention should
      be directed at behavioral characteristics, including hostility, to enhance the
      primary and particularly the secondary prevention of coronary heart disease.

PMID- 10918861
TI  - Patient satisfaction with electroconvulsive therapy.
AB  - OBJECTIVE: To determine whether patients who have electroconvulsive therapy (ECT)
      are satisfied with their treatment and demonstrate more favorable attitudes about
      ECT compared with controls. PATIENTS AND METHODS: We developed a 44-item survey
      measuring ECT treatment satisfaction and attitudes. The survey was administered
      to 24 psychiatric inpatients near the end of ECT treatment and 2 weeks later. A
      modified survey was administered to 24 outpatient controls who had never received
      ECT and who were recruited from a psychiatry clinic waiting room. RESULTS:
      Patients who received ECT had positive attitudes about it. For example, 21 (91%)
      of 24 patient respondents endorsed the statement, "I am glad that I received
      ECT." Attitude score was significantly higher for the ECT group compared with
      controls. A higher degree of satisfaction was associated with a higher level of
      education and younger age. CONCLUSIONS: Patients who received ECT were satisfied
      with their treatment and had more favorable attitudes about it than patients who
      did not receive this treatment.

PMID- 10918862
TI  - Long-term fracture risk among women with anorexia nervosa: a population-based
      cohort study.
AB  - OBJECTIVE: To determine if fractures represent an important problem for women
      with anorexia nervosa who may fail to achieve peak bone mass and may experience
      premature bone loss from decreased estrogen levels. PATIENTS AND METHODS: In this
      population-based retrospective cohort study, we identified 208 Rochester, Minn,
      residents that were first diagnosed as having anorexia nervosa between 1935 and
      1989, whose subsequent fractures were documented in contemporary medical records
      and compared with expected numbers of fractures (standardized incidence ratios
      [SIRs]). RESULTS: Subjects were followed up for 2689 person-years during which
      time 45 patients suffered 88 fractures. Fracture risk was increased among the 193
      women (SIR, 2.9; 95% confidence interval, 2.0-3.9) as well as the 15 men (SIR,
      3.4; 95% confidence interval, 1.1-7.9). The cumulative incidence of any fracture
      at 40 years after the diagnosis of anorexia nervosa was 57%. Fractures of the
      hip, spine, and forearm were late complications, occurring on average 38, 25, and
      24 years, respectively, after diagnosis. CONCLUSION: Young women with anorexia
      nervosa are at increased risk of fractures later in life. Greater attention
      should be paid to the skeletal health of these individuals.

PMID- 10918863
TI  - Patients' concerns prior to undergoing total hip and total knee arthroplasty.
AB  - OBJECTIVE: To document and examine the concerns patients have prior to undergoing
      primary total hip or total knee arthroplasty in a tertiary care center or an
      orthopedic private practice group. PATIENTS AND METHODS: In this prospective
      survey, 136 patients from a tertiary care center and 130 from an orthopedic
      private practice group completed a questionnaire covering 54 items regarding
      their concerns prior to undergoing primary total hip or total knee arthroplasty.
      Patients responded on a visual analog scale, and concern was ranked by mean
      responses (1, not concerned at all; 2, somewhat concerned; 3, very concerned; or
      4, extremely concerned). RESULTS: Responses to only 6 items averaged scores
      higher than 1.9: pain immediately after the surgery (2.07), length of recovery
      (2.07), ability to walk as much as you wish (2.03), ability to return to
      recreational activities (1.97), ability to go up and down stairs (1.94), and risk
      of getting acquired immunodeficiency syndrome from a transfusion (1.92). Older
      patients (> or = 65 years) were less concerned than younger patients (< 65 years)
      in 34 of the 54 questions asked. Women were more concerned than men in 19 of the
      54 questions asked. CONCLUSION: These data provide information that will be
      helpful in preoperative patient discussions and in development of educational
      materials for patients undergoing total hip or total knee arthroplasty.

PMID- 10918864
TI  - Varicella zoster viral disease.
AB  - Herpes zoster is cause of considerable morbidity, especially among elderly
      patients, with a suggestion of a slight increase in incidence among female
      patients. Substantial research on the biology of the varicella zoster virus has
      led to advances in our knowledge of the pathophysiology of the disease along with
      more successful therapy for the acute episodes of herpes zoster. Ophthalmic
      zoster is more common than zoster in other cranial nerves and is associated with
      pronounced suffering. This article reviews the epidemiology, biology, and latency
      of herpes zoster, discusses the pathophysiology of the disease, and describes
      treatment options with antivirals and corticosteroids. The pathophysiology and
      treatment options for postherpetic neuralgia are also addressed. The varicella
      vaccine is now available, and initial results suggest that this may lessen the
      effect of herpes zoster in the future.

PMID- 10918865
TI  - Endovascular repair of abdominal aortic aneurysms: where do we stand?
AB  - Endovascular repair of abdominal aortic aneurysms has evolved dramatically within
      the past few years. In light of the potential to reduce morbidity and mortality
      associated with open surgical repair, endoluminal grafting offers therapeutic
      options to patients who are not surgical candidates because of comorbidities.
      With the development of bifurcated devices, more complex aneurysms may be treated
      by endovascular grafting. Although successful placement of endovascular grafts
      requires a pronounced learning curve, including appropriate patient selection,
      midterm results seem consistent with those of traditional open repair of
      aneurysms. This review describes the current indications, minimal requirements,
      different devices and associated techniques, and potential complications of
      endoluminal repair of abdominal aortic aneurysms. Future aspects of endoluminal
      grafting are also discussed.

PMID- 10918866
TI  - Nonulcer dyspepsia: what it is and what it is not.
AB  - Nonulcer dyspepsia is a description of persistent or recurrent upper abdominal
      pain or discomfort with no structural or biochemical explanation for the
      patient's symptoms. The exact cause of nonulcer dyspepsia is not known, but many
      myths have evolved regarding its etiology and treatment. The goal of this review
      is to evaluate the potential causes of nonulcer dyspepsia. By determining what it
      is and what it is not, we can be more selective in our approach to diagnosis and
      our choice of empiric therapies.

PMID- 10918867
TI  - Daniel Bovet--Nobel laureate in medicine.

PMID- 10918868
TI  - Improved coronary risk assessment with electron beam computed tomography in an
      asymptomatic female with familial hypercholesterolemia.
AB  - An asymptomatic 36-year-old woman had high cholesterol levels due to heterozygous
      familial hypercholesterolemia (FHC) and a family history of coronary artery
      disease (CAD) but no other risk factors. Exercise testing showed no signs of
      ischemia. Conventional drug therapy did not lower lipid levels adequately.
      However, low-density lipoprotein (LDL) apheresis, which effectively reduces
      cholesterol levels in patients with heterozygous FHC, was not indicated,
      according to current guidelines. Electron beam computed tomography demonstrated
      exceptionally high amounts of coronary calcium for the patient's age and sex. A
      subsequent coronary angiogram revealed advanced CAD, which justified the
      initiation of LDL apheresis to reduce her cholesterol levels. In patients with
      heterozygous FHC refractory to conventional lipid-lowering therapy, the presence
      of coronary calcium in the highest percentiles for age and sex (i.e., > 75th
      percentile) may warrant aggressive clinical management to improve prognosis, even
      if no symptoms or signs of ischemia are present.

PMID- 10918869
TI  - Breast-feeding with ectopic axillary breast tissue.
AB  - Axillary breast tissue, which may be an extension of the tail of Spence, is a
      normal variant that has been reported in the literature relatively infrequently,
      although it may be present in a number of asymptomatic women. If axillary breast
      tissue becomes symptomatic, this usually occurs during pregnancy or immediately
      postpartum when a woman begins breast-feeding. Symptoms are swelling and pain due
      to engorgement. A literature review revealed that management is generally
      conservative, with cessation of breast-feeding to allow regression of the tissue.
      This report describes a woman who successfully pumped her axillary breasts to
      relieve pain and engorgement; this allowed her to continue breast-feeding for
      several weeks. Axillary breast tissue should be monitored for pathologic change.

PMID- 10918870
TI  - 17-year-old female adolescent with abdominal pain and fever.

PMID- 10918871
TI  - The fluoroquinolones.
AB  - The quinolones are broad-spectrum antibacterial agents that have a novel
      mechanism of action. As synthetic compounds, these agents have been developed
      extensively to optimize antimicrobial activity, pharmacokinetic properties, and
      drug safety. Although earlier quinolones were effective only in the genitourinary
      and gastrointestinal tracts and only had activity against aerobic gram-negative
      bacteria, newer quinolones have wider potential applications and a broader
      spectrum of activity. Some of the newer quinolones will have a role in the
      treatment of community-acquired pneumonia and intra-abdominal infections.
      Ciprofloxacin remains the most potent quinolone against Pseudomonas aeruginosa.
      Among the quinolones, important differences exist in renal and hepatic
      elimination and dose-adjustment regimens. Although there are many Food and Drug
      Administration-approved indications for some of the newer quinolones, the
      quinolones are the drug of choice for only a few infections. Quinolone-resistant
      bacteria are being increasingly identified and emerge under selective pressure
      created by extensive use.

PMID- 10918872
TI  - Antimycobacterial therapy.
AB  - Tuberculosis is a major cause of illness and death worldwide. The epidemic of the
      acquired immunodeficiency syndrome and the increased number of other
      immunocompromised hosts have led to a remarkable increase in Mycobacterium avium
      intracellulare complex infections. Adequate diagnostic, prevention, and treatment
      measures are available; however, resources for implementing these measures are
      limited. Processes for using these limited resources are not always well
      organized. This review of prevention and treatment of tuberculosis, including the
      six major recommendations from the Centers for Disease Control and Prevention,
      treatment of certain other mycobacterial infections, and information on some
      antimycobacterial agents, such as isoniazid, rifampin, rifabutine, pyrazinamide,
      and ethambutol, was written mainly for primary-care providers.

PMID- 10918873
TI  - Snoring and sleep quality: everyone deserves a good night's rest.

PMID- 10918874
TI  - Amoxicillin-clavulanic acid: additions and corrections.

PMID- 10918875
TI  - The Carney eponym.

PMID- 10918876
TI  - Managed care--not the answer.

PMID- 10918877
TI  - Legalising assistance with dying in South Africa.

PMID- 10918878
TI  - The 'Internet print-out syndrome'.

PMID- 10918879
TI  - Plastic and reconstructive surgery--the spectrum of practice.

PMID- 10918880
TI  - Are Bartonella emerging and re-emerging pathogens in southern Africa?

PMID- 10918881
TI  - Occupational disease gap.

PMID- 10918882
TI  - Greed versus health.

PMID- 10918883
TI  - The Presidential AIDS Advisory Panel meeting: a personal view.

PMID- 10918884
TI  - Big five to cut cost of AIDS drugs.

PMID- 10918886
TI  - Scanning for cash--kickbacks in radiology.

PMID- 10918885
TI  - Guidelines for tuberculosis preventive therapy in HIV infection. Consensus
      guidelines from a workshop, 29-30 October 1999. HIV Clinicians Society of
      Southern Africa.

PMID- 10918887
TI  - Murder by medical malice--the love-hate relationship between Dr Harold Shipman
      and his patients.

PMID- 10918888
TI  - Implementing children's constitutional health care rights fairly.

PMID- 10918889
TI  - Spinal/epidural haematomas associated with neuraxial anaesthesia in the presence
      of heparin and low-molecular-weight heparins.

PMID- 10918890
TI  - Genital schistosomiasis presenting as suspected ectopic pregnancy in the Western
      Cape.

PMID- 10918891
TI  - Lumbar puncture is dangerous in patients with brain abscess or subdural empyema.

PMID- 10918892
TI  - Community knowledge and perceptions about malaria and practices influencing
      malaria control in Mpumalanga Province, South Africa.
AB  - OBJECTIVE: To assess community knowledge and perceptions about malaria and its
      control in a rural setting. DESIGN: Descriptive cross-sectional survey. SETTING:
      Tonga district with a population of 116,418, seasonal malaria with an annual
      incidence of 3,200 cases. SUBJECTS: Female heads of 299 randomly selected
      households. METHODOLOGY: A total of 299 households were selected from a random
      sample of 30 clusters. Community knowledge and perceptions about malaria and its
      control were assessed by interviews with the female head of each of the 299
      selected households. RESULTS: Respondents ranked malaria as the third most
      serious health problem facing the community after TB and AIDS. Seventy-two per
      cent (214/299) of respondents reported that they knew what malaria disease was
      and of these, 92.1% (197/214) mentioned mosquito bites as the cause of malaria.
      The respondents' understanding of the causal role of mosquitoes in malaria was
      significantly related to their knowledge about disease symptoms (P < 0.001).
      Reported community compliance with the malaria control programme (MCP) was
      satisfactory; 86.6% (259/299) of respondents reported that their homes had been
      sprayed during the past 2 years but 10.0% (30/299) did not know why homes were
      sprayed. Hospitals or clinics were the facilities where respondents most commonly
      sought treatment for fever; 66.9% (200/299) reported that they would seek
      treatment immediately after the onset of high fever. Specific practices such as
      replastering or washing of inside walls compromised the effectiveness of the MCP.
      Personal preventive measures were sometimes used against malaria (50.8%, 152/299)
      and use was positively associated with education level (P = 0.001). Respondents
      expressed their desire for more information about malaria and their willingness
      to contribute to the control of malaria in their community. CONCLUSION: The
      survey collected information which was directly relevant to the development of
      health education messages to increase community awareness of the problem of
      malaria, to emphasise the importance of early diagnosis and prompt treatment of
      malaria, to improve community understanding of the function of indoor residual
      spraying, and to enlighten the population of the role of mosquitoes in malaria
      transmission and the availability and benefits of personal protection measures
      against mosquito bites.

PMID- 10918893
TI  - Long-term domiciliary oxygen therapy--the Johannesburg Hospital experience.
AB  - OBJECTIVES: To assess the clinical and demographic characteristics of patients
      attending an oxygen clinic, to assess the relevance of the current clinical
      criteria determining the need for domiciliary oxygen, to assess the cost
      effectiveness of an oxygen clinic and to assess compliance with the oxygen
      prescription. DESIGN: Descriptive study with a retrospective review of data.
      SETTING: Tertiary-level academic hospital. SUBJECTS: All patients attending a
      newly established oxygen clinic. RESULTS: Data were analysed for 679 patients
      (361 male and 318 female), of whom 543 were ex- or current smokers, and 136 were
      non-smokers. Of the total number, 576 had chronic obstructive pulmonary disease.
      Oxygen was given to 425 patients and denied to 254. Forced expiratory volume in 1
      second (FEV1) is probably not of value in determining requirement for oxygen as
      there was no correlation between severity of lung disease and partial arterial
      oxygen pressure (PaO2). There was also no correlation between PaO2 and litres of
      oxygen prescribed. Compliance with the oxygen prescription was 39%. Cost savings
      to the State from the oxygen that was not prescribed was in the region of
      R125,000 per month. CONCLUSIONS: Each patient should be assessed individually
      using clinical parameters to classify the disease severity and to assess the
      degree of tissue hypoxia. Oxygen clinics are of value and should be established
      more widely within each province. Compliance is suboptimal and continued follow
      up to motivate patients to use the oxygen as prescribed should be instituted.

PMID- 10918894
TI  - Hepatitis C virus infection in chronic haemodialysis patients--relationship to
      blood transfusions and dialyser re-use.
AB  - BACKGROUND: A high prevalence of hepatitis C virus (HCV) infection has been
      observed in haemodialysis units. Many studies have demonstrated an association
      with blood transfusions, but other data suggest that nosocomial transmission also
      occurs. There is disagreement as to what measures are necessary to prevent
      nosocomial spread. METHODS: In 1992 we commenced screening of patients for
      antibodies to HCV (anti-HCV) using a second-generation enzyme-linked
      immunosorbent assay (ELISA) test. Positive patients were not confined to special
      machines or units and all dialysers were re-used. RESULTS: The prevalence of anti
      HCV declined from 16.4% in 1992 to 5.3% in 1995 (P = 0.04). At both times, anti
      HCV-positive patients, when compared with negative patients, had a longer mean
      time on haemodialysis (1992: 101.6 (standard deviation (SD) = 57.4) months v.
      30.3 (32.4); 1995: 105.5 (23.9) v. 30.2 (32.8) months) and a greater mean number
      of blood transfusions (1992: 22.6 (18) v. 6.8 (9.4) units; 1995: 14.8 (3.6) v.
      4.5 (7.1) units). When the 1992 and 1995 groups were compared there was no
      difference in time on haemodialysis (mean 42 months v. 34.2 months), but there
      was a significant reduction in the mean number of blood transfusions (mean 9.4
      (12.5) v. 5.0 (7.2), P = 0.03). CONCLUSIONS: We attribute the decline in
      prevalence of HCV seropositivity mainly to the introduction of screening of blood
      donations and a decline in the number of blood transfusions. The reduction in
      prevalence occurred despite routine re-use of dialysers and lack of isolation of
      seropositive patients, suggesting that in the setting of low overall prevalence,
      neither factor contributed significantly to the transmission of HCV. Clearly the
      possibility of some nosocomial transmission could not be totally excluded.

PMID- 10918895
TI  - The evaluation of public psychiatric services in three provinces of South Africa.
AB  - OBJECTIVES: To describe the quality of care in community- and hospital-based care
      in three provinces in terms of 13 standards of care and the criteria associated
      with each; and to explore the similarities and differences between provinces.
      DESIGN: A descriptive study in the form of a survey using interviews, observation
      and questionnaires. SETTING: Three provinces of South Africa, namely Gauteng,
      KwaZulu-Natal and the Eastern Cape. In each of the provinces hospitals and
      clinics were the focus of the study. SUBJECTS: The person heading the mental
      health service in each province completed a questionnaire about the services in
      the province. Consumers (both direct consumers and family) received
      questionnaires or were interviewed if illiterate. In each province a sample of
      hospital units and clinics was visited and interview and observation schedules
      were completed. OUTCOME MEASURES: Thirteen previously tested standards of care
      were addressed covering a comprehensive array of indicators of care. Management,
      research and development, structural and process standards were included.
      RESULTS: All three provinces fared well for three standards (staff attitudes,
      process of hospital admission and availability of forensic care). On another
      three all the provinces fared poorly (management, regular review and/or
      evaluation of services, and research activity). In terms of clinic services all
      three provinces scored low for the availability of weekend and emergency services
      and psychosocial rehabilitation. In terms of hospital care the criteria referring
      to human rights of patients produced the lowest scores. CONCLUSIONS: The paucity
      of management information on some aspects makes planning and evaluation
      difficult. However, the report does indicate specific areas that need improvement
      in each province.

PMID- 10918896
TI  - Nutritional status and dental caries in a large sample of 4- and 5-year-old South
      African children.
AB  - BACKGROUND: Evidence from studies involving small samples of children in Africa,
      India and South America suggests a higher dental caries rate in malnourished
      children. A comparison was done to evaluate wasting and stunting and their
      association with dental caries in four samples of South African children. DESIGN:
      Cross-sectional study based on random sampling of birth records of two age bands.
      METHODS: A total of 2,728 4- and 5-year-old South African children from one rural
      community and three urban communities were examined for nutritional status and
      dental caries. RESULTS: In the total sample prevalences of wasting were mild
      (28%), moderate (4%) and severe (2%). For stunting the prevalences were mild
      (13%), moderate (3%) and severe (1%). For both conditions rural children showed
      higher proportions than the other groups. Statistical analysis showed
      statistically significant differences for wasting and stunting between the study
      groups. No significant association was found between the prevalence of caries and
      stunting or wasting, but an association was noted between wasting and decayed,
      missing and filled (dmf) surfaces (P = 0.003). CONCLUSIONS: In the series of
      children studied, nutritional status was not found to be clinically relevant to
      dental caries prevalence and experience.

PMID- 10918897
TI  - [5th Annual meeting of the Austrian Society of Endocrinology and Metabolism. St.
      Wolfgang, 27-29 April 2000. Abstracts].

PMID- 10918898
TI  - Uterine bacteriology, histology, resumption of ovarian activity and granulocyte
      function of the postpartum cow in different milking frequencies.
AB  - The postpartum uterine bacteriology, histology, resumption of ovarian activity
      and polymorphonuclear granulocyte (PMN) number and function in 18 Swedish dairy
      cows were studied. Cows were milked either 2x (n = 9) or 3x per day (n = 9).
      Endometrial biopsy samples for bacteriological and histological investigations
      were collected during 8 weeks postpartum, starting within one week after calving.
      Milk samples for progesterone determination were collected twice a week until the
      cows had shown normal reproductive cyclicity. Blood samples for granulocyte
      function (phagocytic capacity and total number) were collected from each animal
      on the same days as when the biopsies were obtained. All animals in both groups
      were free from bacteria at the latest after 6 weeks post-partum and there was no
      difference regarding bacterial elimination and bacterial species between milking
      groups. No difference regarding uterine histology between milking groups was
      seen. In both groups, 8 cows had normal to slight infiltration of leukocytes in
      the endometrium at the end of sample collection. No changes in granulocyte
      function could be seen in the 2 milking groups. Resumption of ovarian activity
      was detected on day 45.6 +/- 9.3 (mean +/- SD) postpartum in the 2x milking group
      and 36.6 +/- 9.0 (mean +/- SD) post-partum in the 3x milking group (p = 0.05).
      Based on our findings, an increased milking frequency from 2 to 3 times a day did
      not influence the uterine function postpartum.

PMID- 10918899
TI  - Response of Corriedale ewes to the "ram effect" after priming with
      medroxyprogesterone, fluorogestone, or progesterone in the non-breeding season.
AB  - One hundred eighty-nine Corriedale ewes were used during the non-breeding season
      to study the "ram effect" stimulus after priming with progestogens. Intravaginal
      sponges containing either medroxyprogesterone acetate (MAP group, n = 49),
      fluorogestone acetate (FGA group, n = 49), or progesterone devices (CIDR group, n
      = 46) were inserted on Day-6 (Day 0 = introduction of the rams). Forty-five ewes
      were untreated and kept as a control group. On Day 0 the sponges were removed and
      rams provided with marking harnesses for oestrous detection were placed with the
      ewes. Onset of estrus was monitored until Day 25, and conception was determined
      by transrectal ultrasonography. Ewes came into heat during 4 periods: Days 0-3, 5
      7, 17-20, and 21-23. The overall number of oestrus ewes were 29%, 53%, 35%, and
      50% for the control, MAP, FGA, and CIDR groups, respectively (MAP and CIDR >
      control, p < 0.05). Control ewes presented oestrus only on Days 17-20 and 21-23.
      Oestrus in the progestogen-primed ewes was concentrated during Days 0-3 and 17
      20, and some ewes came into oestrus on Days 5-7. There were no differences
      between different primings neither in oestrous response nor in conception rate.
      The conception rate from matings occurring on Days 0-3 was higher than on those
      occurring on Days 17-20. We conclude that MAP, FGA, and CIDR is equally effective
      in improving the response to the ram effect, and the pattern of oestrus in primed
      ewes was different than previously reported.

PMID- 10918900
TI  - Mortality in farmed mink: systematic collection versus arbitrary submissions for
      diagnostic investigation.
AB  - The distribution of diagnoses of mortality in mink submitted to the Danish
      Veterinary Laboratory (DVL) for diagnostic investigation in the calendar year
      1997 was compared with the diagnoses of mortality in all dead mink collected at 4
      selected farms (project farms) during the same period. A total of 1,015 submitted
      mink and 1,149 mink from the 4 project farms were subjected to post mortem
      investigation. The average size (breeding stock) of the project farms was larger
      than Danish farms on average. However, the distribution of colour types of the
      mink was comparable. The seasonal distribution of the material from project farms
      and that of the submissions were approximately the same. Differences in the
      distribution of diagnoses as well as recovered microorganisms were found,
      however, mainly related to the proportion of gastro-intestinal disorders and E.
      coli respectively. These proportions were negatively correlated. Overall the
      results showed that extrapolating diagnostic results of laboratory submissions to
      the population of farmed mink may be problematic, and more reliable methods for
      disease surveillance must be considered.

PMID- 10918901
TI  - Identification of coagulase-positive staphylococci isolated from bovine milk.
AB  - A total of 414 coagulase-positive staphylococcal strains obtained at the mastitis
      laboratory, National Veterinary Institute, Uppsala, Sweden, were studied. One
      hundred and seventy seven strains were used for a frequency study. Ninety-seven
      per cent were identified as Staphylococcus aureus, 2% as Staphylococcus
      intermedius and 1% as Staphylococcus hyicus. Two hundred and thirty seven strains
      with atypical hemolysis reactions on bovine blood agar were randomly selected,
      with the aim to increase the number of S. intermedius and S. hyicus strains
      available for testing. Eight different characteristics, including physiological,
      enzymatical and biochemical properties, were used to identify the coagulase
      positive Staphylococcus species. The results of this study suggest that the
      following tests should be included for correct identification of the 3 different
      species of coagulase-positive staphylococci: P agar supplemented with acriflavin,
      beta-galactosidase and hemolytic reaction on chocolate agar. These 3 tests are
      simple and quick to perform and enable accurate for easy differentiation of the 3
      coagulase-positive Staphylococcus species.

PMID- 10918902
TI  - The acute phase protein serum amyloid A (SAA) as an inflammatory marker in equine
      influenza virus infection.
AB  - The acute phase protein serum amyloid A (SAA) has proven potentially useful as an
      inflammatory marker in the horse, but the knowledge of SAA responses in viral
      diseases is limited. The aim of this study was to evaluate SAA as a marker for
      acute equine influenza A2 (H3N8) virus infection. This is a highly contagious,
      serious condition that inflicts suffering on affected horses and predisposes them
      to secondary bacterial infections and impaired performance. Seventy horses,
      suffering from equine influenza, as verified by clinical signs and
      seroconversion, were sampled in the acute (the first 48 h) and convalescent (days
      11-22) stages of the disease, and SAA concentrations were determined. Clinical
      signs and rectal temperature were recorded. Secondary infections, that could have
      influenced SAA concentrations, were clinically suspected in 4 horses. SAA
      concentrations were higher in the acute stage than in the convalescent stage, and
      there was a statistically positive relationship between acute stage SAA
      concentrations and clinical signs and between acute stage SAA concentrations and
      maximal rectal temperature. Horses sampled early in the acute stage had lower SAA
      concentrations than those sampled later, indicating increasing concentrations
      during the first 48 h. There was a statistically positive relationship between
      convalescent SAA concentrations and degree of clinical signs during the disease
      process. The results of this investigation indicate that equine SAA responds to
      equine influenza infection by increasing in concentration during the first 48 h
      of clinical signs and returning to baseline within 11-22 days in uncomplicated
      cases.

PMID- 10918903
TI  - Effects of immobilization with medetomidine and reversal with atipamezole on
      blood chemistry of semi-domesticated reindeer (Rangifer tarandus tarandus L.) in
      autumn and late winter.
AB  - Blood chemistry was studied in 8 adult female reindeer, of which 5 were pregnant.
      Half of them received only medetomidine (150 micrograms/kg i.m.) and half of them
      medetomidine and atipamezole (750 micrograms/kg) in March. Three weeks later the
      drug regimens were reversed. The same procedure was carried out during the next
      September and October. Seasonal differences in pretreatment values could be seen
      in serum urea, phosphorous, and cholesterol, with the highest concentrations
      during the autumn; and creatinine, ASAT, ALAT, and CK values, which were higher
      in the non-pregnant reindeer in late winter. Their low-protein and low-energy
      diet during the winter explains most of the differences. Increased enzyme
      activities in serum indicate decreased membrane stability of certain organs in
      late winter, possibly due to nutritional deficiencies. Treatment effects could be
      seen in several parameters. The increase in blood glucose and decrease in serum
      FFA were most probably due to alpha 2-adrenoceptor activation, which inhibits
      insulin release and lipolysis. These effects were partly or totally inhibited
      after treatment with the antagonist atipamezole. The earlier increase in serum CK
      and ASAT activities in those receiving atipamezole can be explained by increased
      tissue perfusion due to atipamezole itself and the fact that these animals stood
      up and began to move much earlier than did those which received medetomidine
      only. A significant decrease in serum Na+, K+, Cl-, Pi, cholesterol, total Ca,
      and total protein concentration observed during the first 10 to 40 min of the
      medetomidine sedation could be explained by possible haemodilution and diuresis.
      More effective metabolism of medetomidine in autumn could explain the shorter
      recovery times of reindeer receiving only medetomidine and most of the
      differences in treatment effects between the seasons: faster increase in protein
      and cholesterol concentrations after the decrease, and the antagonistic effect of
      atipamezole on glucose and Pi changes in autumn. Based on these results,
      medetomidine seems to be a good sedation agent for reindeer both in autumn and in
      late winter; the effects of medetomidine can be rather effectively antagonized by
      atipamezole.

PMID- 10918904
TI  - A case of ovine tick-borne fever in December in Norway.

PMID- 10918905
TI  - In vitro sensitivity of the swine Brachyspira species to tiamulin in Finland 1995
      1997.

PMID- 10918906
TI  - [Q fever: not just in sheep].
AB  - Four patients, a woman aged 41 years and 3 men aged 12, 47 and 44 years,
      developed high fever after returning from a farm vacation in the Ardeche
      (France). They also suffered from severe headache, a painful tightness of the
      chest, abdominal pain or myalgia. Other symptoms were shivers, tiredness and a
      cough. While physical examination revealed few abnormalities, the chest X-ray in
      3 patients showed an atypical pneumonia. One of these patients developed dural
      venous sinus thrombosis with increased intraspinal pressure. This patient also
      showed signs of a slight hepatitis. Serological investigation revealed that all 4
      patients were suffering from acute Q fever, a zoonosis caused by the Coxiella
      burnetii bacterium. All 4 had been present at lambing and sheep-shearing. The
      patients with pneumonia were treated with antibiotics. All 4 patients recovered
      well. It is known that animal birth products in particular can contain large
      numbers of bacteria and therefore be highly infectious.

PMID- 10918907
TI  - ['Informed consent' and prerandomization].
AB  - The usual procedure in randomised controlled trials is to obtain informed consent
      first, after which participants can be randomised. The reversal of the order,
      first randomisation and then informed consent, is called pre-randomisation (Zelen
      design). In the Netherlands, there is discussion as to whether pre-randomisation
      should be allowed in medical research. Full informed consent regarding the design
      of the investigation may lead to unwanted loss of distinction between the
      experimental and control groups, thus reducing the internal validity of the
      investigation. A possible solution could be to include, in the informed consent
      procedure, the statement that certain information has been withheld because
      revealing it now would make the investigation useless, but that it will be
      revealed to all participants afterwards and that the study design was approved by
      the medical ethics committee. In this way, the advantage of the enhanced internal
      validity of the pre-randomisation design is retained while simultaneously keeping
      intact the sequence of first informed consent and then randomisation.

PMID- 10918909
TI  - [Depression following a heart infarct and increased risk of death].
AB  - Depression is an important risk factor for cardiac mortality, especially in the
      first 18 months after a myocardial infarction. Listlessness and a hostile mood
      are the specific features of the depression following myocardial infarction,
      rather than depressed mood. Also, depressed post infarction patients are more
      often re-admitted for cardiac reasons and their work resumption is delayed. There
      are indications that depression and myocardial infarction have an aetiological
      relationship via the behavior and emotions that are a risk factor for the
      development of both disorders. Depression and myocardial infarction are both
      stress-related disorders. A pathological stress reaction is seen in both
      conditions and triggers immune activation, enhanced blood cortisol levels,
      disturbance of serotonin metabolism and increased sympathetic activation. Early
      detection of post-infarction depression and treatment with a selective serotonin
      reuptake inhibitor (SSRI) is advised. SSRIs have been shown to be efficacious and
      safe in this patient population. Tricyclic antidepressants (TCAs) are relatively
      contra-indicated due to their cardiac side effects. As yet, no therapeutic effect
      of antidepressants, in the sense of decreased cardiac mortality or a decrease in
      fatal rhythm disorders, has been demonstrated.

PMID- 10918908
TI  - [Acute and chronic Q fever; epidemiology, symptoms, diagnosis and therapy of
      infection caused by Coxiella burnetii].
AB  - Q fever is a zoonosis caused by Coxiella burnetii, an obligate intracellular
      bacterium. Domestic ungulates and parturient cats are the primary reservoirs of
      infection. The animals excrete the bacterium in urine, faeces, milk and amniotic
      fluid. After desiccation the micro-organism spreads via aerosols. After
      inhalation or ingestion and an incubation period of 2-6 weeks acute Q fever may
      develop with atypical pneumonia and hepatitis as major clinical symptoms. The
      infection also may present as a flu-like illness or remain asymptomatic.
      Generally, the prognosis is favourable. However, endocarditis or another chronic
      form of Q fever occasionally develops with possibly fatal outcome. Diagnosis
      relies upon serologic testing with an indirect immunofluorescence method.
      Doxycycline is the antibiotic of choice in the treatment of Q fever. Endocarditis
      needs therapy for years with the addition of rifampin or hydroxychloroquine. Q
      fever is poorly recognised due to the variety of clinical presentations.

PMID- 10918910
TI  - [Roaming through methodology. XIX. Cost-effectiveness ratios].
AB  - A number of aspects must be kept in mind when interpreting cost-effectiveness
      ratios; it is important to realise, for example, that a cost-effectiveness ratio
      is a relative and not an absolute measure of efficiency. A cost-effectiveness
      ratio always involves a comparison of two interventions; therefore, the choice of
      the competing alternative has great impact on the reported, 'incremental', cost
      effectiveness ratio and requires careful study. Furthermore, a cost-effectiveness
      ratio is meant to support a choice or decision. A check must be done to see
      whether the study context and the resulting cost-effectiveness ratio are
      appropriate for the choice or decision under consideration.

PMID- 10918911
TI  - [Favorable results of surgical treatment of mucoid cysts of the fingers and thumb
      in 20 patients, Leyenburg Hospital, Den Haag, 1992-99].
AB  - OBJECTIVE: Evaluation of the surgical treatment of mucoid cysts of the fingers
      and thumb. DESIGN: Retrospective, descriptive. METHOD: In 20 patients admitted to
      the Leyenburg Hospital in the Hague during the period 1992/'99, 24 mucoid cysts
      were treated by surgical excision and simultaneous removal of any pre-existing
      joint irregularities (osteophytes). Relevant data were collected after an average
      follow-up period of 2.5 years (range: 3 months-8 years) by a review of the
      charts, a physical examination and a questionnaire. RESULTS: The 20 patients
      included 13 women and 7 men with an average age of 74 years (range: 42-84). On
      follow-up examination they reported decreased pain in 8 of the 10 previously
      painful fingers and improved function in 8 of the 9 fingers with previous
      function limitation. Physical examination revealed an improvement in digital
      excursions in 8 of the 9 patients with a pre-operative function limitation and a
      decreased mobility in 18 of the 24 cysts. Nail abnormalities had been present in
      11 patients; these all disappeared following the operation. Of the 20 patients,
      17 were very and 3 were moderately satisfied with the results of the operation.
      No recurrences were seen during the follow-up period. CONCLUSION: The results of
      the surgical technique used were: no recurrences, no more pain or restricted
      movement in most patients. Other symptoms, such as longitudinal groove in the
      nail, recurrent discharge of the cyst and cosmetic imperfections, were
      counteracted successfully.

PMID- 10918912
TI  - [Fecal incontinence: prevalence and role of rupture of the anal sphincter during
      delivery; literature analysis].
AB  - OBJECTIVE: To obtain insight regarding the prevalence of faecal incontinence
      according to age and sex and the influence of an anal sphincter rupture during
      vaginal delivery on its development. METHOD: Literature search in Medline (1966
      May 1998), Huisarts en Wetenschap (1972-1997) and Nederlands Tijdschrift voor
      Geneeskunde (1986-1997). RESULTS: The prevalence of faecal incontinence was 0.75
      2.2% of the adult population, increasing to 2.8-9% at the age of 65 years and
      older. Among people aged 85 years and older and those living in homes for the
      aged, the prevalence was much higher (up to 16.7%). There was no clear difference
      between the sexes, but dependable research on sex differences at a younger age
      did not exist. There was a significantly higher risk of developing faecal
      incontinence after an intrapartum anal sphincter rupture, compared to women
      without an anal sphincter rupture. This difference persisted until 30 years
      postpartum, but disappeared afterwards. A possible explanation is a persistent
      anal sphincter defect, despite surgical repair immediately postpartum. Decreased
      innervation of the sphincter may also play a role. CONCLUSION: Faecal
      incontinence is a frequent problem, especially in the elderly. There is no clear
      sex difference in prevalence. In younger women, there is a higher risk of
      developing faecal incontinence after an anal sphincter rupture during a vaginal
      delivery. This is probably due to a persistent sphincter defect in combination
      with decreased innervation of the sphincter.

PMID- 10918913
TI  - [Two patients with chronic lymphocytosis of large granular lymphocytes; benign or
      premalignant?].
AB  - In two female patients aged 44 and 86 years, a chronic lymphocytosis was observed
      caused by a proliferation of large granular lymphocytes (LGL). The first one had
      been successfully treated for Hodgkin lymphoma long before, the second had
      diabetes mellitus type 2. Immunophenotyping showed the proliferating lymphocytes
      to be natural killer (NK) cells. In contrast to the proliferation of B- and T
      lymphocytes, data on the prognosis and treatment of NK-lymphocytosis are very
      scarce. A literature search revealed three major clinical entities in which LGL
      proliferate: at one end of the spectrum we see the very aggressive NK-LGL
      leukaemia, at the other, NK-lymphocytosis, a benign chronic disorder, in between
      is the relatively indolent chronic T-LGL leukaemia. Both patients suffered from
      chronic NK-lymphocytosis with a favourable course; there were no further symptoms
      4 and 2 years, respectively, after the diagnosis. In cases of prolonged
      lymphocytosis of unknown origin, immunophenotyping of the lymphocytes is
      essential. Only in this way can one arrive at the proper diagnosis and reach
      conclusions as to the prognosis and the possible methods of treatment.

PMID- 10918915
TI  - FDA admits to lacking control over counterfeit drug imports.

PMID- 10918914
TI  - [Asymptomatic dilatation of the pyelocaliceal system in young children, detected
      by ultrasonography; altered insights and current management].

PMID- 10918916
TI  - FDA approves single-injection, bolus-dose thrombolytic agent.

PMID- 10918917
TI  - Prehospital thrombolysis may improve chances of short-term survival, meta
      analysis shows.

PMID- 10918918
TI  - Nonabsorbed polymer approved for reducing high cholesterol levels.

PMID- 10918919
TI  - Guidelines address management of lipid disorders associated with antiretroviral
      therapy.

PMID- 10918920
TI  - Reference on the extended stability of injectable drugs for home care.

PMID- 10918921
TI  - Safety and efficacy of antiestrogens for prevention of breast cancer.
AB  - The rationale for clinical trials of antiestrogens for prevention of breast
      cancer, potential concerns with antiestrogens, and clinical trials of
      antiestrogens for breast cancer prevention are discussed. Extensive preclinical
      evidence supports clinical investigation and use of tamoxifen for preventing
      breast cancer. The efficacy of tamoxifen in the treatment of advanced breast
      cancer and as adjuvant therapy has further strengthened the rationale for use in
      prevention. Tamoxifen is well tolerated and, like raloxifene, has been associated
      with non-cancer-related benefits. The major concerns with tamoxifen are an
      increased risk of thromboembolic events and endometrial cancer and an association
      with ocular disorders. Little is known about the long-term safety of raloxifene.
      Three randomized, double-blind, placebo-controlled clinical trials of tamoxifen
      20 mg (as the citrate) daily for the prevention of breast cancer and one post hoc
      analysis and a literature review examining the effect of raloxifene on breast
      cancer risk (as a secondary endpoint) have been published. In one of the three
      trials of tamoxifen, the rate of invasive breast cancer was reduced 49%; in the
      other two trials, no reduction in breast cancer was found. Raloxifene apparently
      reduced the frequency of breast cancer. On the basis of the positive tamoxifen
      trial, tamoxifen can be offered to women with a five-year projected risk of
      breast cancer of > or = 1.67%, as determined by the Gail model. Risks and
      benefits should be evaluated for each patient. Tamoxifen may offer some women
      protection against breast cancer. Raloxifene may also have a preventive role, but
      more study is needed.

PMID- 10918922
TI  - Home care pharmacy: extending clinical pharmacy services beyond infusion therapy.
AB  - A clinical pharmacy program was developed at an established home health care
      (HHC) agency to demonstrate the need for clinical pharmacy services in the HHC
      population and to explore opportunities for providing pharmaceutical care beyond
      infusion-related therapies. Initial experiences of this pilot project are
      described. Patients were found to be primarily elderly (mean age, 70 years) and
      to use a substantial number of medications. While only 11% of patients referred
      to the agency required infusion therapy, multiple opportunities for pharmacist
      involvement in patient care were identified and a variety of projects were
      undertaken. A drug information service was developed, a retrospective evaluation
      of patients with congestive heart failure led to an interventional study, a
      cisapride intervention was implemented, home vancomycin monitoring was assessed,
      pharmaceutical care services were provided to patients enrolled in a long-term
      home care program, a pain management initiative was begun, adverse drug reactions
      were identified and reported, and pharmacists participated in agency policy
      development. Preliminary data suggest that pharmacist involvement positively
      affected patient care. Drug information was provided on 232 occasions. Cisapride
      was discontinued in five patients with contraindications to the agent.
      Comprehensive pharmacotherapy assessments were performed on 29 long-term-care
      patients, generating 129 therapy recommendations of which 33% were accepted.
      Pharmacists working with a home care agency identified numerous opportunities for
      improving patient care. Many of the patients receiving home care services were
      elderly, took a substantial number of medications, and were at risk for drug
      related problems and suboptimal therapy.

PMID- 10918923
TI  - Development of an indinavir oral liquid for children.
AB  - An indinavir oral liquid was developed and studied. Several oral liquids
      containing indinavir were prepared and taste tested in eight healthy volunteers.
      Physical and chemical stability over two weeks were examined, and a randomized,
      two-way-crossover, single-dose bioequivalence trial was performed in 12 healthy
      male volunteers. Indinavir 800 mg was given as two 400-mg indinavir capsules
      (Crixivan) on day 1 and as 80 mL of the indinavir liquid on day 2, or vice versa.
      A standard breakfast and lunch were given at fixed times, and blood and urine
      samples were collected at various intervals up to eight hours. The log
      transformed area under the concentration-versus-time curve from zero to eight
      hours (AUC0-8) and maximum plasma concentration (Cmax) for the liquid versus the
      capsules were compared by using a 90% confidence interval (CI) test (limits, 80
      125%), and the time to Cmax (tmax) was compared by using the nonparametric sign
      test. The liquid selected had an acceptable taste, contained indinavir 10 mg/mL,
      and was chemically stable for two weeks at 4 degrees C. The 90% CI for the AUC
      ratio (liquid versus capsules) was 92-99% (mean, 95%); for the Cmax ratio it was
      95-106% (mean, 100%). There was no significant difference in tmax between the
      liquid and capsules. An oral liquid formulation of indinavir was developed that
      had an acceptable taste, was chemically stable, and was bioequivalent to the
      commercially available capsule.

PMID- 10918924
TI  - Stability of famotidine in an extemporaneously compounded oral liquid.

PMID- 10918925
TI  - ASHP guidelines on the safe use of automated compounding devices for the
      preparation of parenteral nutrition admixtures. Developed through the ASHP
      Council on Professional Affairs and approved by the ASHP Board of Directors on
      April 27, 2000.

PMID- 10918926
TI  - Problems with the automatic switching of generic cyclosporine oral solution for
      the innovator product.

PMID- 10918927
TI  - A glimpse of pharmacy practice in Japan: deja vu.

PMID- 10918928
TI  - Survey of alternative and nonprescription therapy use.

PMID- 10918929
TI  - Currentness of foreign-drug list.

PMID- 10918930
TI  - Two decades of insider research: what we know and don't know about chronic
      illness experience.
AB  - Chronic illness in a general sense and certain chronic diseases in particular
      have attracted considerable attention from qualitative researchers in nursing as
      well as in other health and social sciences. This review critically examines the
      body of available research about the experience of living with a chronic illness
      from an "insider" perspective. From this foundation the authors interpret the
      manner in which this large body of writing both contributes to and complicates
      our theoretical understanding of what it is like to live with a chronic disease.
      In so doing they illuminate themes within the knowledge that can be gleaned from
      qualitative inquiry into the chronic illness experience, as well as inherent
      limitations that must be taken into consideration when applying such knowledge to
      practice.

PMID- 10918931
TI  - Children with epilepsy: quality of life and psychosocial needs.
AB  - In this chapter, research related to quality of life in children with epilepsy
      and their psychosocial needs is reviewed. Nursing and nonnursing research reports
      and descriptions of instruments developed between January 1994 and February 1999
      are included. Most research reports described quality-of-life problems,
      especially psychological functioning in school-age children. Less attention was
      devoted to psychosocial needs. Major gaps included intervention studies and
      research on infants and young children. Conclusions include recommendations for
      future research.

PMID- 10918932
TI  - Adherence in chronic disease.
AB  - Nonadherence to treatment regimen is a prevalent problem of patients with chronic
      disorders. Approximately half of the patients with a chronic disease have
      problems following their prescribed regimen to the extent that they are unable to
      obtain optimum clinical benefit. This chapter reviews the state of knowledge
      regarding adherence to chronic disease regimens across the life span and
      demonstrates that the extent and nature of the adherence problems are similar
      across diseases, across regimens, and across age groups. Adherence to the
      commonly prescribed regimens is addressed, including pharmacological therapies,
      therapeutic diets, and therapeutic exercise. Randomized, controlled studies
      focusing on various educational, behavioral, cognitive, and affective
      interventions to improve adherence are included. Based on this review, further
      work is needed to better understand and improve adherence. New strategies for
      analysis and measurement will support these needed advances in the field of
      adherence.

PMID- 10918933
TI  - Heart failure management: optimal health care delivery programs.
AB  - Heart failure is the single most costly health care expenditure in the United
      States. The major proportion of these costs is attributable to
      rehospitalizations, and by many estimates the majority of rehospitalizations
      might be preventable with better health care delivery. The past 5 years have seen
      an explosion in the number of heart failure disease management programs put in
      place across the country to try to decrease the economic burden of heart failure
      and improve patient outcomes. Yet few of these are based on programs tested by
      researchers, let alone tested in randomized, controlled trials. This chapter
      summarizes findings from studies of heart failure disease management programs
      from 1980 to the present, critiques those studies, and offers suggestions for
      future research in this area.

PMID- 10918934
TI  - Cancer care: impact of interventions on caregiver outcomes.
AB  - The purpose of this review is to examine the research literature on interventions
      aimed at caregivers who, in the current health care environment, are assuming
      increasing responsibility for the complex care of significant others experiencing
      cancer. The general aim of the review is to synthesize the literature on
      interventions targeted to cancer caregivers and to summarize outcomes associated
      with the various intervention strategies described. Three broad categories of
      interventions were described in the literature: (1) educational, (2)
      counseling/psychotherapeutic, and (3) hospice and palliative home care. The
      review included studies that met the following criteria: data-based studies that
      described an intervention aimed at assisting caregivers to care for patients with
      cancer, studies published between 1975 and January 1999, and studies published in
      English. A total of 29 published papers was included. Although the original
      intent was to limit the review to studies that associated interventions with
      outcomes, a lack of well-delineated outcome variables was revealed as a major gap
      in the literature. Thus, some studies that did not include outcome variables were
      reviewed and the following conclusions made: (1) there is a dearth of data-based
      literature describing interventions aimed at caregivers; interventions that are
      described often lack well-defined effects due to a lack of or poor
      operationalization of outcomes; (2) of the small number of studies in this area,
      many used small samples and lacked randomization; and (3) studies often revealed
      selection bias to well-adjusted caregivers who were accepting of support, able to
      obtain respite care in order to participate, and often willing to avail
      themselves of a group-style intervention.

PMID- 10918935
TI  - Interventions for children with diabetes and their families.
AB  - The purpose of this review is to examine the research literature on interventions
      for children with type 1 diabetes and their families, with a specific focus on
      three types of intervention (educational and psychosocial/behavioral
      interventions that focus on individuals with diabetes and family interventions
      for families, usually parents, of individuals with diabetes). The aim of the
      review is to determine what interventions produce what outcomes in what
      populations of children and families. The review includes articles that met the
      following criteria: (a) empirical study reporting the impact of an intervention
      on such outcomes as knowledge, behavior, self-care, and metabolic control; (b)
      children with type 1 diabetes and/or their families as primary subjects; (c)
      publication between 1980 and January 1, 1999; and (d) publication in English. A
      total of 41 published papers were included. On the basis of this review,
      conclusions are as follows: (a) Educational interventions are useful in improving
      diabetes knowledge but not consistently helpful in improving metabolic control;
      (b) psychosocial interventions, especially coping skills training and peer
      support, assist primarily adolescents to improve adjustment and sometimes
      metabolic control; and (c) family interventions may be helpful in reducing parent
      child conflict about diabetes management and care.

PMID- 10918936
TI  - Management of urinary incontinence in adult ambulatory care populations.
AB  - During the past decade, research on urinary incontinence and its management has
      grown significantly. Behavioral therapy is now viewed as an important first line
      of treatment for stress, urge, and mixed urinary incontinence. This chapter
      provides a critical review of the intervention studies on lifestyle
      modifications, bladder training, and pelvic floor muscle training conducted in
      adult ambulatory care populations that were published in 1988 through 1999.
      Recommendations for future research are provided.

PMID- 10918938
TI  - School-based interventions for primary prevention of cardiovascular disease:
      evidence of effects for minority populations.
AB  - The purposes of this review were to analyze and evaluate the results of school
      based studies that have used population-wide approaches for primary prevention of
      cardiovascular diseases and to assess the extent to which strategies tested to
      date have been effective for minority populations in the United States. The
      literature included in the review was restricted to studies published between
      1986 and August 1999; they sampled elementary, middle, or high school students
      and incorporated a control or comparison group. There were no consistent effects
      of school-based interventions on blood pressure, lipid profiles, or measures of
      body mass and obesity. There was evidence that changes in knowledge and health
      behaviors occurred. Findings are interpreted within the context of population
      wide approaches to prevention, and recommendations for future research directions
      are discussed.

PMID- 10918937
TI  - Family interventions to prevent substance abuse: children and adolescents.
AB  - Substance abuse often begins in adolescence and is a major factor determining
      health outcomes for adolescents and adults; thus, it is an important focus for
      prevention strategies. The use of drugs, especially alcohol, can lead to chronic
      addiction to substances as well as contribute to a number of common chronic
      conditions. These conditions include cancer, cardiovascular disease, disability
      from accidents or violence, and unplanned pregnancy and are major causes of
      morbidity and mortality among adolescents and adults. As the major social unit
      responsible for socialization of children and stabilization of adult
      personalities, the family has been the target of prevention efforts. In this
      chapter the empirical literature on family interventions to prevent substance use
      in adolescents is critically reviewed, generalizations and implications for
      practice identified, and directions for future research projected.

PMID- 10918939
TI  - Breakthroughs in scientific research: the discipline of nursing, 1960-1999.
AB  - The period of 1960 to 1999 was an era of evolution and rapid growth of scientific
      research in the discipline of nursing during which specific knowledge realms, or
      subfields of the discipline, emerged and scientific breakthroughs occurred. This
      review presents the milestones or scientific breakthroughs of the era in the
      context of the prevailing thinking within and beyond the discipline of nursing.
      The nature of each scientific breakthrough in nursing is characterized as to the
      transdisciplinary change in thinking brought about by the work. The pathfinders
      for each scientific breakthrough are identified as well as their pathfinding
      modes. Opportunities for future scientific breakthroughs in nursing are
      presented.

PMID- 10918940
TI  - Synthesis and binding of 3-aminopyridine derivatives at central nicotinic
      receptors.
AB  - A series of secondary and tertiary pyridyl amides as potential central nicotinic
      acetylcholine receptors (nAChRs) ligands were prepared. Amides displayed
      negligible or very low affinity, whereas two amines achieved by reduction of
      corresponding secondary amides, showed affinity in the nanomolar range for
      nAChRs.

PMID- 10918941
TI  - Neurotoxic effects of interleukin-6 and sodium nitroprusside on cultured rat
      hippocampal neurons.
AB  - The neurotoxicity of interleukin-6 (IL-6) and sodium nitroprusside (SNP, CAS
      13755-38-9) was examined using primary cultures of rat hippocampal neurons. The
      cell viability was significantly reduced after the cultures were co-incubated
      with IL-6 4, 40, 400 ng/ml or SNP 1, 10, 100 mumol/l for 24 h. In addition, N
      omega-nitro-L-arginine (NNA, CAS 2149-70-4) at 0.1 mmol/l, when co-added with IL
      6 400 ng/ml in cultures, significantly increased IL-6 reduced viability from 78.3
      +/- 6.7% to 113.3 +/- 10.0%. These results indicate that IL-6 exerts
      neurotoxicity on cultured hippocampal neurons probably via overformation of
      nitric oxide in cultures.

PMID- 10918942
TI  - Hemodynamic effects of intravenous administration of olprinone hydrochloride on
      experimental pulmonary hypertension.
AB  - To examine acute effects of olprinone hydrochloride (CAS 106730-54-0, Coretec) on
      pulmonary hypertension, hypoxic pulmonary hypertension was produced in 6 adult
      Beagle dogs. Using this pulmonary hypertension model, single intravenous bolus
      injections of olprinone at doses of 10, 30 and 100 micrograms/kg were
      administered at 5-min intervals and hemodynamic parameters were evaluated. Heart
      rate increased at doses of 30 and 100 micrograms/kg, but did not change at a dose
      of 10 micrograms/kg. Mean aortic pressure, mean pulmonary arterial pressure,
      pulmonary vascular resistance and systemic vascular resistance and right
      ventricular stroke work index did not change at doses of 10 and 30 micrograms/kg,
      but they decreased significantly at a dose of 100 micrograms/kg. On the other
      hand, cardiac index and the first derivative value of the left ventricular
      pressure did not show significant change at all doses. These results indicate the
      vasodilating effects on peripheral and pulmonary vessels in hypoxic model at high
      doses of olprinone. Its application in right heart failure accompanied by
      pulmonary hypertension therefore is expected to yield promising results.

PMID- 10918943
TI  - Developmental toxicity of the class III antiarrhythmic agent almokalant in mice.
      Adverse effects mediated via induction of embryonic heart rhythm abnormalities.
AB  - Almokalant (ALM, CAS 123955-10-2), a class III antiarrhythmic drug, has been
      shown to be embryotoxic in rats. In the absence of human pregnancy outcome data,
      the human relevance of these findings in rats is unknown, and results from other
      species would indicate if these findings are of more universal interest.
      Therefore, this study was initiated to evaluate the potential effects in mice.
      ALM was given to three groups of pregnant mice (approximately 20 mice/group)
      during gestation days 6-15 at dose levels of 50, 125 and 300 mumol/kg. A fourth
      group served as a control. In addition, whole embryo culture was performed on
      gestation day 10 with doses of ALM ranging from 325-5200 nmol/l (approximately 17
      embryos/group) in order to study if ALM had the potential to induce dysrhythmia
      in the embryonic mouse heart. ALM induced total embryonic death in the high dose
      group, and in the intermediate group the level of embryonic death was elevated
      and the mean foetal weights decreased. A slight increase in minor skeletal
      defects was observed, mainly consisting of reduced calcification of elements in
      the vertebral column and among the phalanges. ALM caused bradycardia in a
      concentration dependent manner (13-42% at 650-5200 nmol/l). Irregular heart
      rhythm and/or episodes of cardiac arrest were observed in one embryo at 2600 and
      in seven embryos at 5200 nmol/l. In conclusion, ALM caused embryotoxicity in the
      mouse, most likely secondary to adverse effects on the embryonic heart. The
      results may suggest that class III antiarrhythmics are embryotoxic also in
      humans.

PMID- 10918944
TI  - Angiotensin II analogues with sulphur-containing side-chains in position 5. A
      structure-activity relationship study.
AB  - Four sets of angiotensin II (AngII) analogues with position 5 modifications, two
      agonist series with either Asp or Sar in position 1 and L-Phe in position 8, and
      two antagonist series with again Asp or Sar in position 1 and Leu in position 8
      were synthesized. Modifications in positions 5 were introduced successively: Ile,
      Nle, Met, S-ethyl Cys, S-n-propyl-Cys, S-n-butyl Cys, S-t-butyl Cys and S-benzyl
      Cys in all four series. The study was undertaken in order to investigate the 5
      position residue of AngII by replacing the hydrophobic side-chain by another
      containing an electrophilic moiety. The analogues were synthesised by solid phase
      synthesis using the Boc/Bzl or Fmoc/But strategy. All analogues were evaluated by
      their binding properties to the AT1 receptor on bovine adrenocortical membranes
      (bAT1). The results indicate that AngII analogues bind, irrespective of their
      agonistic or antagonistic nature or of their position 1 modification, in a
      similar manner and that position 5 modifications without beta-branching behave in
      an additive manner towards their affinity.

PMID- 10918945
TI  - Long-term effect of antihypertensive therapy with calcium antagonist or
      angiotensin converting enzyme inhibitor on serum nitrite/nitrate levels in human
      essential hypertension.
AB  - Endothelial function is impaired in hypertension. In the present study the
      effects of long-term antihypertensive therapy on endothelial production of nitric
      oxide (NO) were investigated. Fifteen untreated mild to moderate essential
      hypertensive patients and 13 normotensive subjects were enrolled in this study.
      Blood pressure, heart rate, lipid profiles, cyclic guanosine 3', 5'-monophosphate
      (cGMP) and nitrite/nitrate (NOx), which are stable metabolites of NO, were
      measured. The hypertensive patients were treated with a calcium antagonist,
      benidipine (CAS 91559-74-5) (Ca group: n = 8) or an angiotensin converting enzyme
      inhibitor, trandolapril (CAS 87679-37-6) (ACEI group: n = 7) and 12 weeks after
      the treatment the same examinations were performed. NOx and cGMP levels in
      hypertensive patients were significantly lower than those in normotensive
      subjects (32.3 +/- 4.1 versus 49.0 +/- 6.5 mumol/l and 2.16 +/- 0.39 versus 3.39
      +/- 0.42 pmol/ml, respectively). Both antihypertensive agents decreased the
      elevated blood pressure (mean blood pressure; 120 +/- 3 to 99 +/- 3 mmHg in Ca
      group and 117 +/- 4 to 104 +/- 4 mmHg in ACEI group) and normalized the decreased
      NOx and cGMP levels (29.1 +/- 6.2 to 46.2 +/- 8.6 mumol/l and 1.96 +/- 0.37 to
      3.20 +/- 0.71 pmol/ml in Ca group, 36.0 +/- 5.3 to 54.7 +/- 6.9 mumol/l and 2.45
      +/- 0.52 to 2.87 +/- 0.43 pmol/ml in ACEI group, respectively). Either benidipine
      or trandolapril improves the endothelial function and increases the impaired
      basal release of NO in hypertension. This suggests the beneficial effects of the
      drugs on protection against the vascular complications in hypertension.

PMID- 10918946
TI  - Effects of beraprost and cilostazol and renal function on serum thrombomodulin
      levels in diabetic patients.
AB  - Serum thrombomodulin (TM) levels were determined in diabetic patients, and the
      effects of diabetic complications and renal function on TM were studied. Serum TM
      levels increased in diabetics, and patients with diabetic nephropathy tended to
      manifest higher levels of TM. There was a significant correlation between TM and
      serum creatinine levels. In addition, there was a significant elevation in serum
      TM levels in diabetics over time (1 year to 1 year 8 months), and the changes
      were particularly evident in patients who had a higher TM level from before the
      observation period. Furthermore, when patients were treated with an antiplatelet
      agent--beraprost (CAS 88475-69-8) or cilostazol (CAS 73963-72-1)--a significant
      reduction in TM levels was observed after 3 months. It is suggested that TM could
      be used as index to assess the development of clinical complications in diabetics
      and that anti-platelet agents have potential usefulness in delaying the
      aggravation of diabetic complications.

PMID- 10918947
TI  - Synthesis and hypoglycemic activity of some new flavone derivatives. 2nd
      communication: 4'-flavonyl-2,4-thiazolidinediones.
AB  - A new series of 4'-flavonyl-2,4-thiazolidinedione, 2,4-imidazolidinedione and 2
      thiohydantoin derivatives (1-10) were synthesized. Their chemical structures have
      been elucidated by IR, 1H-NMR, mass spectra and elementary analysis. The
      synthesized compounds were tested for their insulinotropic effects in INS-1
      cells. Inhibitory effects were observed for compounds 1, 2, 6 and 7.

PMID- 10918948
TI  - Synthesis of methylamino-2-phenyl-2-butyl-3,4,5-trimethoxybenzoate, the main
      bioactive metabolite of trimebutine maleate.
AB  - The first synthesis of the methylamino-2-phenyl-2-butyl-3,4,5-trimethoxybenzoate
      (desmethyltrimebutine) I is described. This compound is the main bioactive
      metabolite of trimebutine II (Debridat, CAS 39133-31-8), an antispasmodic widely
      used for intestinal diseases since 1969. It was used for pharmacokinetic and
      bioequivalence studies.

PMID- 10918949
TI  - Synthesis and antisecretory activity of 6-substituted 5-cyanomethylimidazo[2,1
      b]thiazoles and 2,6-dimethyl-5-hydroxymethylimidazo[2,1-b][1,3,4]thiadiazole.
AB  - The synthesis of imidazo[2,1-b]thiazole and imidazo[2,1-b][1,3,4]thiadiazole
      derivatives, related to known antiulcer agents, is reported. 5-Cyanomethyl-6
      methylimidazo[2,1-b]thiazole showed significant antisecretory activity in the
      isolated rabbit gastric glands assay.

PMID- 10918950
TI  - Role of guanylyl cyclase activation via thiamine in suppressing chemically
      induced writhing in mouse.
AB  - The possible role of L-arginine/nitric oxide (L-arginine/NO) pathway in the
      antinociceptive activity of thiamine (vitamin B1) in p-benzoquinone-induced mouse
      writhing model was investigated. Thiamine (ED50, 0.11 mg/kg), L-arginine (50
      mg/kg), NG-nitro L-arginine methyl ester (L-NAME, 75 mg/kg) and morphine (ED50:
      0.13 mg/kg) displayed antinociceptions following s.c. administrations (52.4 +/-
      5.5%, 36.8 +/- 7.7%, 27.8 +/- 11.1%, 66.1 +/- 3.5%, respectively). However,
      methylene blue (MB, 40 mg/kg, s.c.) produced a nociception (-32.1 +/- 9.9%).
      Coadministration of B1 with L-arginine did not significantly change L-arginine
      induced antinociception (48.9 +/- 3.7%). Cotreatment of thiamine with L-NAME and
      MB significantly increased the L-NAME-induced antinociception (53.9 +/- 3.9%) and
      reversed the MB-induced nociception to antinociception (46.0 +/- 4.2%). L
      Arginine and L-NAME-induced antinociceptions were significantly increased (55.9
      +/- 3.9% and 61.1 +/- 5.0%, respectively) by morphine. MB-induced nociception
      significantly reversed to antinociception by the concomitant administration of
      morphine (41.6 +/- 8.9%). Thiamine and morphine coadministration displayed
      antinociception (46.0 +/- 4.2%). The present results suggest that thiamine could
      produce antinociception by the activation of guanylyl cyclase mediated by cyclic
      guanosine monophosphate (cGMP) that may trigger the possible involvement of
      central and/or peripheral L-arginine/NO/cGMP pathway.

PMID- 10918951
TI  - Bioequivalence of inhaled formoterol fumarate assessed from pharmacodynamic,
      safety and urinary pharmacokinetic data.
AB  - This paper deals with a crossover trial on healthy volunteers performed to obtain
      combined pharmacodynamic, safety and pharmacokinetic data in order to assess the
      bioequivalence of formoterol fumarate (CAS 43229-80-7) delivered by mono-dose dry
      powder inhalers, as test and reference. The trial was carried out on 24 Caucasian
      healthy male and female volunteers treated with 12 micrograms formoterol fumarate
      bihydrate capsules for inhalation route. Pharmacodynamics was evaluated through a
      challenge test with methacholine on the forced expiratory volume in 1 s (FEV1).
      Safety was achieved from glucose and potassium serum levels assayed on timed
      samples over a 12-h period cost-dosing and from blood pressure, heart rate and
      ECG recording. Pharmacokinetics was obtained from urinary excretion of
      formoterol, assessed by a highly sensitive analytical method (LC-MS-MS).
      Pharmacodynamic, safety and pharmacokinetic results evidenced the bioequivalence
      of the two formulations investigated. This investigation is an interesting
      approach how to assess bioequivalence when the classical approach based on the
      similarity of plasma concentrations can not be applied.

PMID- 10918952
TI  - Synthesis and activity of new acylated diaminohydroxyalkanes as human
      immunodeficiency virus protease inhibitors.
AB  - A series of HIV-1 protease inhibitors based on the lead compound Pc (IC50 = 165
      nmol/l) with structural modifications at P1/P1' substituents or with a
      lengthening at its core unit were synthesized from amino acid starting materials.
      All analogues were less active than Pc against the protease.

PMID- 10918953
TI  - Synthesis and antimicrobial activity of 4-carbethoxymethyl-2-[(alpha
      haloacyl)amino] thiazoles and 5-nonsubstituted/substituted 2-[(4
      carbethoxymethylthiazol-2-yl)imino]-4-thiazolidinones.
AB  - 4-Carbethoxymethyl-2-[(chloroacetyl/alpha-chloropropionyl/al pha-
      bromobutyryl/alpha-chloro-(alpha-phenylacetyl)amino]thiazoles (I-IV) were
      synthesized by reacting 4-carbethoxymethyl-2-aminothiazole with chloroacetyl
      chloride, alpha-chloropropionyl chloride, alpha-bromobutyryl bromide and alpha
      chloro-alpha-phenylacetyl chloride, respectively. Furthermore, I-IV were refluxed
      with ammonium thiocyanate to give 2-[(4-carbethoxymethylthiazol-2-yl)imino]-4
      thiazolidinones (V-VIII). V was refluxed with various aromatic aldehydes to give
      5-arylidene-2-[(4-carbethoxymethylthiazol-2-yl)imino]-4-t hiazolidinones (IX
      XIV). The structures of synthesized compounds were confirmed by elemental
      analyses, hydrolysis, UV, IR, 1H-NMR and EI mass spectral data. The antimicrobial
      activities of the compounds were assessed by microbroth dilution technique using
      Mueller-Hinton broth and Mueller-Hinton Agar. In this study, Staphylococcus
      aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC
      8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539,
      Salmonella typhi, Shigella flexneri, Proteus mirabilis and Candida albicans ATCC
      10231 were used as test microorganisms. Among the tested compounds, XI and XIV
      showed activity against S. aureus (MIC: 78 micrograms/ml, 1.6 micrograms/ml),
      whereas compound V had an activity against S. flexneri (MIC: 39 micrograms/ml)
      and compound I against C. albicans (MIC: 125 (micrograms/ml). Compounds I, IV-XIV
      were also evaluated for antituberculosis activity against Mycobacterium
      tuberculosis H37Rv using the BACTEC 460 radiometric system and BACTEC 12B medium.
      Only compounds I and XIV showed 86% and 67% inhibition in the primary screen.

PMID- 10918954
TI  - Effect of polyoxyl 35 castor oil and Polysorbate 80 on the intestinal absorption
      of digoxin in vitro.
AB  - Surfactants are classically used to improve the solubilization of lipophilic
      drugs such as digoxin. Polysorbate 80 and Cremophor EL (polyoxyl 35 castor oil)
      are such surfactants but they may also modulate the action of P-glycoprotein, an
      energy-dependent "counter-transport" system implicated in the phenomenon of
      multidrug resistance in cancer cells. P-glycoprotein is also present in the
      intestine on the apical membrane of mature enterocytes and can potentially reduce
      the absorption of a wide range of drugs. In this study, using the improved
      everted gut sac method, the effects of Polysorbate 80, Cremophor EL and
      cyclosporin on the absorption of digoxin were studied. An increase in the uptake
      of digoxin in the presence of these three products could be shown with our in
      vitro model. Cremophor EL and Polysorbate 80 had no toxic effects at the
      concentrations used. These results suggest that surfactants such as Cremophor EL
      and Polysorbate 80 should not only support solubilization but can also modulate
      the P-glycoprotein system to improve the bioavailability of poorly absorbed
      drugs.

PMID- 10918955
TI  - The epidemiology of knee dislocations.
AB  - The traumatically dislocated knee can be a devastating injury; fortunately, it is
      uncommon. More attention is being given to the treatment of knee dislocations as
      the capability of ligamentous reconstruction increases. Great treatment advances
      are anticipated as this interest grows and outcomes are evaluated. Nonetheless,
      the complications of this injury, including loss of limb, still occur from the
      missed diagnosis of a knee dislocation. MR imaging and other technological
      advances do not relieve the clinician of the responsibility for performing a
      thorough physical examination. Suspicion of an associated neurovascular injury
      must always be high. To a certain degree, prevention of this injury may be
      possible in the high-velocity accidents that occur with motor vehicles and in
      industry. Advancement in vehicular designs, with specific attention to airbags,
      dashboards, and firewalls, needs to be made to reduce the incidence and magnitude
      of lower extremity trauma in motor vehicle accidents. Seat belts remain the most
      effective restraint in the prevention of lower extremity trauma in the motor
      vehicle.

PMID- 10918956
TI  - Historic perspectives of treatment algorithms in knee dislocation.
AB  - Knee dislocation remains a devastating injury with many complications. It
      necessitates prompt diagnosis, reduction if needed, and emergent repair of any
      vascular injury. Serial physical examinations and frequent use of arteriograms
      are necessary to avoid late vascular complications. Many authors are concerned
      that normal pulses, normal Doppler signals, and normal ABIs have preceded late
      ischemia and documented intimal tear, demonstrated by arteriography. More
      recently, other authors have challenged the gold standard of mandatory
      arteriography by describing studies in which physical examination was 100%
      accurate in diagnosing patients without operative vascular injury. If pedal
      pulses, Doppler signals, or ABIs are asymmetric before or after reduction then
      either immediate operative exploration or arteriography should be performed. If
      the initial physical examination is normal, serial examinations are used in the
      hospital to check for late artery thrombosis. Opponents of mandatory
      arteriography point to a 5% false-negative rate, high cost, and an 8%
      complication rate, such as contrast allergy, pseudoaneurysm, local hematoma, and
      arteriovenous fistula. Today a consensus is that repair and reconstruction of the
      PCL and posterolateral corner injuries are the primary concerns in the multiple
      ligament injured knee after dislocation. The ACL may be repaired later if
      instability persists, but some investigators believe it should not be repaired
      acutely, thereby avoiding increased surgical trauma and possible stiffness.
      Recently one of the goals of ligamentous repair and reconstruction has been to
      provide stability with the least invasive surgical technique to avoid
      postoperative stiffness. Recent treatments have focused on early arthroscopic
      assisted allograft reconstruction of the ACL and PCL. Allograft provides a less
      invasive means of graft support than autograft. Early, limited range of motion in
      a brace helps to maintain flexion and extension.

PMID- 10918957
TI  - Physical diagnosis of the multiple-ligament-injured knee.
AB  - Knee dislocations and related knee trauma represent dramatic orthopedic injuries.
      The severity and spectrum of injury may not be immediately evident to the
      clinician. A high index of suspicion for associated neurovascular involvement
      must be maintained throughout the initial care of the patient. In anticipation of
      ligament repair and reconstruction, a preoperative MR imaging study supplemented
      by an examination under anesthesia allows for an accurate assessment of the
      pattern and severity of ligament injury. With this knowledge the surgeon is able
      to prepare properly for surgery and create appropriately placed surgical
      incisions to afford adequate exposure of all injured structures.

PMID- 10918958
TI  - Imaging of the multiple-ligament-injured knee.
AB  - Imaging of the multiple-ligament-injured knee requires a comprehensive assessment
      of ligaments, cartilage, bone, peripheral nerves, and vascular anatomy. It is
      imperative that the radiologist be a crucial part of the trauma team, to provide
      prompt diagnostic assistance without unnecessary delays in patient management. MR
      angiography remains a promising modality to detect vascular injury and provides
      arteriographic assessment with little risk to the patient in a more expeditious
      fashion than conventional contrast angiography.

PMID- 10918959
TI  - Low-velocity knee dislocation with sports injuries. Treatment principles.
AB  - Knowing that the injured MCL and PCL can heal and that the injured ACL and
      lateral side, predictably, will not heal are the bases for the treatment approach
      to these injuries. (1) Allow MCL healing nonoperatively. (2) Allow PCL healing to
      occur as long as PCL laxity is 2+ or less (reconstruct the PCL acutely if
      posterior drawer is > 2+ initially). (3) Initially delay ACL treatment and
      reconstruct later, if needed posterior drawer. (4) Perform acute lateral side
      repair to reattach structures to their distally torn site.

PMID- 10918960
TI  - High-velocity knee dislocation with vascular injury. Treatment principles.
AB  - A high-velocity knee dislocation is a true orthopedic emergency. A high index of
      suspicion is necessary to identify reduced knee dislocations in multiple trauma
      patients. Coexisting injuries are common in patients with high-velocity knee
      dislocations. After an initial assessment, the knee joint should be reduced
      immediately and splinted. Popliteal artery injury is common in high-velocity
      dislocations. Arteriograms can be helpful but should not delay operative
      treatment of obvious arterial injuries. Early restoration of flow to the ischemic
      limb will avoid amputation in most patients. The orthopedic surgeon must consider
      a variety of approaches when treating a patient with this type of injury. A
      spanning external fixator is a useful method for temporary immobilization in knee
      dislocation patients who have open dislocations, arterial repairs, or closed head
      injuries. Early surgery to improve the functional stability of the knee must be
      balanced against the risk of major surgery in patients with severe lower
      extremity and systemic injuries. The long-term risk of knee stiffness versus
      instability must be considered. Selective, subacute, aggressive collateral
      ligament repair and bicruciate reconstruction with allografts offer the best
      chance for optimal outcome.

PMID- 10918961
TI  - Surgical treatment of combined injury to anterior cruciate ligament, posterior
      cruciate ligament, and medial structures.
AB  - Injuries involving the anterior cruciate, posterior cruciate, and medial
      collateral ligaments represent one combination of injuries representing knee
      dislocation. Prompt reduction and neurovascular evaluation are necessary when
      treating these injuries. Operative management involving reconstruction and repair
      of the injured structures produces optimal results. This article outlines the
      principles involved in evaluating and managing these injuries, combined with
      specifics of the authors' treatment approach, and review of the literature.

PMID- 10918962
TI  - Treatment of combined anterior cruciate ligament-posterior cruciate ligament
      lateral side injuries of the knee.
AB  - ACL-PCL-posterolateral corner injuries most frequently are seen in multiple
      trauma patients but do occur in the athletic injury population. Acute three
      ligament-injured knees may have been tibiofemoral dislocations with spontaneous
      reduction in the field. Careful documentation of the neurovascular status is
      essential in these cases to avoid the complications associated with limb
      ischemia. Systematic evaluation of these patients with history, physical
      examination, imaging studies, examination under anesthesia, and diagnostic
      arthroscopy will aid in the correct diagnosis and treatment plan formulation.
      Arthroscopically assisted, combined ACL-PCL-posterolateral complex
      reconstructions, using strong graft material, and performed in a timely fashion,
      have provided consistent and predictable results with few complications.

PMID- 10918963
TI  - Outcomes of the operatively treated knee dislocation.
AB  - Despite being a serious injury with early complications associated with a high
      degree of morbidity, the outcomes of knee dislocations have improved dramatically
      since the days of Sir Astley Cooper. Currently, most authors favor early surgical
      reconstruction of the injured ligamentous structures. With modern surgical
      techniques and rehabilitation protocols, most patients are able to achieve
      functional range of motion and stability necessary for everyday life. Despite
      improvements in treatment, stiffness and pain, rather than instability, can be a
      problem. Patients continue to have difficulty returning to pre-injury levels of
      athletic competition and manual labor, although a significant number of patients
      have achieved these goals. As physicians, we must be knowledgeable in the current
      surgical techniques and rehabilitation protocols used in the treatment of knee
      dislocations, and the typical prognosis of the injury. By informing our patients
      of hurdles that they will be forced to overcome, in their path to recovery,
      before initiating treatment, patients will better understand the seriousness of
      the injury, which, it is hoped, will lead to compliance with their rehabilitation
      and thus better outcomes.

PMID- 10918964
TI  - Knee dislocation. Complications of nonoperative and operative management.
AB  - Because of the nature and extreme severity of the injury, complications will
      continue to be a common denominator in traumatic knee dislocations. The major
      complications that cause significant morbidity, including amputation and death,
      are now relatively infrequent. Prompt recognition and treatment of these
      complications are of utmost importance to assure functional viability of the
      extremity. These complications must continue to be addressed preoperatively and
      postoperatively. Minor complications will persist after significant knee surgery.
      New complications will evolve as newer techniques, instrumentation, and
      procedures are introduced. Ligament reconstructive surgery is relatively new and
      technically demanding. The surgeon must continue to use meticulous technique and
      attention to detail. Orthopedic surgeons must continue to closely evaluate the
      procedures they perform, making sure they are as technically correct as possible.
      Each surgeon must observe and determine what technique will be of true benefit to
      the patient. Most complications that do occur can be corrected or at least
      improved if they are handled early and with a true understanding of the problem.

PMID- 10918965
TI  - Rehabilitation of the multiple-ligament-injured knee.
AB  - Rehabilitation for a patient with a multiple-ligament knee injury should be
      designed to reduce pain and swelling, restore range of motion, strength, and
      endurance, and to enhance proprioception, and dynamic stability of the knee, with
      the goals of restoring function and minimizing disability. The biomechanics of
      the knee must be considered when designing a rehabilitation program. General
      guidelines for rehabilitation of the multiple-ligament-injured knee include
      considerations for promoting tissue healing, decreasing pain and swelling,
      restoring full motion, increasing muscular strength and endurance, improving
      proprioception, enhancing dynamic stability of the knee, and reducing functional
      limitations and disability. A patient's progression through this sequence must be
      individualized and depends on the pattern of ligament injury or surgical
      procedure that was performed, and the principles of tissue healing. Specific
      guidelines for rehabilitation following ACL reconstruction combined with MCL
      repair, PCL reconstruction, combined ACL-PCL reconstruction, and reconstruction
      of the LCL and posterolateral corner have been provided.

PMID- 10918966
TI  - Current concepts in assessment and treatment of bladder cancer.
AB  - Transitional cell carcinoma of the bladder is comprised of a variety of cancer
      diatheses that manifest a spectrum of distinct biologic potentials. The challenge
      is to control superficial disease recurrence and progression and to identify
      invasive carcinoma at an earlier stage, when it may be more amenable to cure.

PMID- 10918967
TI  - Benign prostatic hyperplasia: challenges for the new millennium.
AB  - The understanding and therapy of benign prostatic hyperplasia (BPH) has become
      more complex recently. The molecular mechanisms and growth factors involved in
      BPH need to be elucidated in the new millennium. The current classification of
      disease reflects the varied pathophysiologic mechanisms causing lower urinary
      tract symptoms (LUTS). In addition, symptom scores have improved evaluation of
      men with BPH, yet 'bother' and 'health-related quality of life' should be better
      recognized as significant outcome parameters. Clinical evaluation with laboratory
      markers specific for BPH or LUTS is currently inadequate. Yet, urodynamic
      evaluation should remain an important aspect of evaluation to guide selection of
      therapy. Recently medical therapy has expanded to include uroselective alpha
      blockade and phytotherapy, yet more research is needed. The most significant
      growth in the field, however, is in minimally invasive therapies of the prostate.
      Long-term comparative prospective multicenter studies are needed to properly
      evaluate the outcomes of new technologies compared to traditional procedures that
      are considered standard of care.

PMID- 10918968
TI  - The evolving role of dendritic cell therapy in urologic oncology.
AB  - The recognition that dendritic cells, the most potent antigen-presenting cells,
      play a pivotal role in the induction of antitumor immunity has reshaped the
      development of tumor vaccines in clinical medicine. Early clinical trials of
      administration of dendritic cell-based vaccines to patients with genitourinary
      malignancies showed low toxicity profiles, and provided evidence for immunologic
      and clinical responses in some patients. Although the development of dendritic
      cell-based vaccines is still in its infancy, the prospects of ultimately
      generating clinically effective cancer vaccines have become more realistic.

PMID- 10918969
TI  - Male sexual dysfunction--the new millennium.

PMID- 10918970
TI  - Diagnosis of localized prostate cancer: 10 years of progress.
AB  - Advances in the diagnosis of early stage disease, and particularly the
      introduction of prostate-specific antigen (PSA) testing, have had a dramatic
      effect on the presentation and clinical management of prostate cancer during the
      past ten years. As a result, there have been significant epidemiological changes
      in countries where early diagnosis is recommended. The importance of PSA testing
      for the diagnosis of localized prostate cancer has become well established in
      clinical practice and this is reflected by improved outcomes from definitive
      treatment. The contribution of PSA-related parameters and molecular forms of PSA
      both to cancer detection and prediction of pathological stage continue to be
      explored. Concerns about the reliability of the standard sextant biopsy technique
      for cancer detection relate to the need for re-biopsy in a growing number of
      patients with negative biopsies and an increasing proportion of patients with low
      volume, multifocal disease. In men with cancer, additional prognostic information
      can be derived from biopsy findings, with important therapeutic implications.
      This relates also to the need for reliable markers indicating pathological stage
      and risk of progression. The opportunities for the prevention of prostate cancer
      have grown with improved understanding of its biology and the genetic basis of
      the early steps associated with malignant transformation. In the future, the need
      for therapeutic intervention is likely to be most influenced by successful
      prevention strategies.

PMID- 10918971
TI  - Sacral neurostimulation and neuromodulation in urological practice.
AB  - The problems associated with treating various forms of lower tract dysfunction by
      electrical stimulation are reflected in the many years of basic and clinical
      research in this area. However, better understanding of both neuroanatomy and
      neurophysiology, and development of new technologies have led to further
      application of electrical current to restore impaired bladder function.
      Contemporary knowledge of the potential for both sacral neurostimulation and
      neuromodulation as a therapeutic option for lower urinary tract dysfunction is
      reviewed.

PMID- 10918972
TI  - The aging male: a challenge for urologists.
AB  - The extension of life expectancy is one of the most dramatic achievements of the
      20th century. Th elderly population, over 65 years, is the fastest growing age
      group. The implication of this population growth will need considerable medical
      and socioeconomic attention during the beginning of this century. A large
      proportion of elderly people are afflicted by several prevalent urological
      diseases such as prostate cancer, benign prostatic hypertrophy, incontinence,
      erectile dysfunction and androgen deficiency. The urologist is in a privileged
      position to play a key role in several medical aspects of the aging male. It is
      the responsibility of the urological community to address the challenge of the
      aging male in the beginning of this new millennium.

PMID- 10918973
TI  - Orthotopic bladder substitution.
AB  - For a select group of patients orthotopic bladder substitution is an ideal
      alternative for urinary diversion after cystectomy. Initially this method was
      mainly applied in males, but is increasingly being used in women with good
      results. In general, consensus has been reached concerning patient selection
      criteria and surgical details, but there are some important issues of continuing
      debate. To achieve good long-term results meticulous postoperative patient
      management is of utmost importance.

PMID- 10918974
TI  - Laparoscopic surgery in urology.
AB  - Not more than 10 years ago, laparoscopy was introduced to the armamentarium of
      urology. The start was slow, with pelvic lymphadenectomy, nephrectomy and
      varicocelectomy being about the only indications. However, very soon great
      enthusiasm developed, and almost every urological operation was performed by
      means of laparoscopy. For several reasons this exaggerated enthusiasm had to be
      followed by disappointment. First of all, laparoscopy turned out not to be as
      easy as many would have liked it to be. Due to a low frequency of operations,
      many surgeons were never able to overcome their learning curve, and the early
      literature reflects this problem. Unlike general surgery where cholecystectomy
      developed into a pacemaker operation, which forced everybody to go ahead with
      laparoscopy, urology was long searching for good and frequent indications for
      this new technique. Within the last few years, the pendulum has swung back to the
      other side. Adrenalectomy was one of the first indications where laparoscopy
      proved superior to open surgery in every aspect. Several other good indications
      have followed, some of which, namely cryptorchidism, nephrectomy and pyeloplasty,
      will be presented in detail to give an example. But the breakthrough that
      recently occurred is due to the success of laparoscopy in the field of oncologic
      surgery. Laparoscopic radical nephrectomy has shown its surgical efficiency as
      well as its oncologic efficacy. However, the main interest is now focused on
      radical prostatectomy, since this is the most frequently performed operation in
      urology by now. Recently this operation could be developed to a standardized
      technique, but only time will tell its true impact. Several indications will
      change in the future, but laparoscopy is here to stay.

PMID- 10918975
TI  - Male infertility: recent advances and a look towards the future.
AB  - The past decade has witnessed clinical and basic scientific advances that have
      revolutionized the diagnosis and treatment of the infertile male. Advances in the
      clinic and laboratory have resulted in men who were previously thought to be
      hopelessly infertile, but who are now able to conceive their own biologic
      offspring. In the future, we believe that the laboratory will continue to play a
      key role in advancing our ability both to diagnose and to treat the infertile
      male. We summarize here some of the major advances of the past decade that have
      influenced our treatment and our understanding of the etiology of male
      infertility. When possible, clinical innovations and advances in basic science
      are discussed in combination in order to emphasize the translational importance
      of reproductive research.

PMID- 10918976
TI  - Description of a presumptive hepatopancreatic reovirus, and a putative gill
      parvovirus, in the freshwater crayfish Cherax quadricarinatus.
AB  - The redclaw freshwater crayfish Cherax quadricarinatus has a reputation for being
      hardy and resistant to handling stress. However, in recent years, possibly since
      1996, C. quadricarinatus farmers in northern Queensland have noted a decrease in
      stress resistance in their stock. A presumptive reovirus in the hepatopancreas,
      and a putative parvovirus in the gills, were associated with chronic mortalities
      in C. quadricarinatus at one northern Queensland farm. Hypertrophic nuclei with
      marginated chromatin were observed in gill epithelium in moribund crayfish which
      had recently been relocated to a laboratory from the holding tank facility on the
      farm. Affected nuclei appeared to be vacant or contained a faint granular
      basophilia in H&E stained sections. However, toluidine blue staining revealed a
      homogeneously granular appearance of the nuclei. Transmission electron microscopy
      revealed approximately 20 nm diameter virus-like particles within the nucleus.
      Eosinophilic, Feulgen-negative, cytoplasmic inclusions were observed in distal
      hepatopancreatocytes in 1 moribund C. quadricarinatus collected from the same on
      farm holding tank approximately 6 mo later. This crayfish did not display the
      gill lesions. Transmission electron microscopy showed that the inclusions
      contained icosahedral virus particles 35 to 40 nm in diameter. The histopathology
      and preliminary virus morphology of the presumptive hepatopancreatic reovirus,
      and the histopathology, ultrastructural pathology and preliminary virus
      morphology of the putative gill parvovirus, are reported herein.

PMID- 10918978
TI  - Isolation of the pathogen Vibrio tapetis and defense parameters in brown ring
      diseased Manila clams Ruditapes philippinarum cultivated in England.
AB  - The Manila clam Ruditapes philippinarum was introduced for aquacultural purposes
      to Europe in the 1970s. In 1987, brown ring disease (BRD), caused by Vibrio
      tapetis, appeared in clams cultivated in Brouenou (Finistere, France) and later
      became increasingly widespread and was reported in cultivated and wild clams
      existing on the Atlantic coasts of France and Spain. The present study reports,
      for the first time, the presence of BRD in clams cultivated in England. The
      etiologic bacterium was isolated and identified using bacteriological and
      serological techniques. The defence response of affected clams was also studied
      and significant changes in the hematological and biochemical characteristics of
      hemolymph and extrapallial fluids were demonstrated. Significant mobilization of
      hemocytes toward the extrapallial fluids, in contact with the main site of
      infection (mantle-periostracal lamina area), was observed, suggesting a role for
      these pseudo-internal compartments in the preservation of clam health.

PMID- 10918977
TI  - Ultrastructure of white spot syndrome virus development in primary lymphoid organ
      cell cultures.
AB  - Primary cell cultures from the lymphoid organ of Penaeus monodon were used to
      investigate in vitro propagation and morphogenesis of white spot syndrome virus
      (WSSV). Double-strength Leibovitz's L15 supplemented with 20% fetal bovine serum,
      pH 7.5, with a final osmolarity of 530 +/- 5 mOsm kg-1 was identified as the most
      suitable culture medium. In this medium, the lymphoid cells remained viable for
      more than 1 wk. Migrating cells were inoculated with WSSV, and the consequent
      cytopathic effects documented by light and electron microscopy. WSSV appears
      capable of following 2 alternative assembly sequences, one similar to the
      morphogenesis of the Oryctes rhinocerus virus and another which is more typical
      of baculoviral assembly. Possible relationships between WSSV, Oryctes virus, and
      baculoviruses are discussed.

PMID- 10918979
TI  - Infectivity, transmission and 16S rRNA sequencing of a rickettsia, Coxiella
      cheraxi sp. nov., from the freshwater crayfish Cherax quadricarinatus.
AB  - A rickettsia-like organism isolated from infected, farm-reared Cherax
      quadricarinatus was cultured in the yolk sac of developing chicken eggs, but
      could not be cultured in 3 continuous cell lines, bluegill fry (BF-2), fathead
      minnow (FHM), and Spodoptera frugiperda (Sf-9). The organism was confirmed by
      fulfilling Koch's postulates as the aetiological agent of mortalities amongst C.
      quadricarinatus. When C. quadricarinatus was inoculated with the organism,
      mortality was 100% at 28 degrees C and 80% at an ambient temperature of 24
      degrees C. Horizontal transmission with food and via the waterborne route was
      demonstrated, but mortalities were lower at 30 and 10% respectively over a 4 wk
      period. The 16S rRNA sequence of 1325 base pairs of the Gram-negative, obligate
      intracellular organism was 95.6% homologous to Coxiella burnetii. Of 18 species
      compared to this rickettsia, the next most closely related bacterium was
      Legionella pneumophila at 86.7%. The suggested classification of this organism is
      Order Rickettsiales, family Rickettsiaceae, tribe Rickettsieae, within the genus
      Coxiella. We suggest it should be named Coxiella cheraxi sp. nov.

PMID- 10918980
TI  - The histopathology and ultrastructure of steatitis affecting common dab Limanda
      limanda.
AB  - This study presents a new description, based on histopathological and
      ultrastructural studies, of a disease affecting the common dab Limanda limanda
      (L.). The condition can be recognised by the presence of multiple orange or
      yellow lesions in the pterygophorial region of the fish. The principal
      histopathological features are necrosis of fat cells, extensive macrophage
      infiltration leading to the formation of granulomatous structures, and the
      accumulation of lipopigment by lipid peroxidation. Based on this description, the
      condition has been diagnosed as steatitis. Although pathology associated with
      lipid peroxidation is the dominant characteristic of the lesions examined, it is
      proposed that this process is secondary to necrosis of the adipose tissue. The
      aetiology is discussed in the light of these observations. In addition, the first
      record of this condition affecting long rough dab Hippoglossoides platessoides
      (Fabricius) is made.

PMID- 10918981
TI  - Associations between epidermal thionin-positive cells and skin parasitic
      infections in brown trout Salmo trutta.
AB  - The dynamics of the densities of epidermal thionin-positive cells (putative mast
      cells) in the skin of brown trout fry were investigated during experimental
      infections with the skin parasites Ichthyophthirius multifiliis (Ciliophora) and
      Gyrodactylus derjavini (Monogenea). It was shown that the metachromatic thionin
      stained cells were extremely sensitive to parasite exposure, as the density of
      cells in the skin of trout decreased markedly after exposure to the pathogens. As
      early as 7 d post infection the cell counts were significantly reduced and almost
      totally depleted following 9 d infection, which suggests that degranulation of
      the cells occurs following parasite exposure. No recruitment of new cells was
      seen during the study period. Some reduction in uninfected control groups
      indicates that the putative mast cells are sensitive to stress as well. A notable
      variation in densities of thionin-stained cells between different fins was found
      and the corneal surface was devoid of these cells. The possible implications of
      these cells in host-parasite interactions are suggested and discussed.

PMID- 10918982
TI  - Commercial trials using emamectin benzoate to control sea lice Lepeophtheirus
      salmonis infestations in Atlantic salmon Salmo salar.
AB  - Two trials were conducted at commercial salmon farms to evaluate the efficacy of
      emamectin benzoate (Slice, 0.2% aquaculture pre-mix, Schering-Plough Animal
      Health) as a treatment for sea lice Lepeophtheirus salmonis (Kroyer) and Caligus
      elongatus Nordmann infestations in Atlantic salmon Salmo salar L. Trials were
      carried out in 15 m2 commercial sea pens, at temperatures of 5.5 to 7.5 degrees C
      and 10.8 to 13.8 degrees C. Each pen was stocked with 14,000 to 17,500 fish with
      mean weights of 0.44 to 0.74 and 1.33 to 1.83 kg. Fish were naturally infested
      with sea lice at the start of each trial. At Day -1, samples of 10 or 15 fish
      were taken from each pen to determine pre-treatment numbers of lice. Emamectin
      benzoate was administered in feed, to 4 replicate pens, at a dose of 50
      micrograms kg-1 biomass d-1 for 7 consecutive days (Days 0 to 6). Sea lice were
      counted again, between Days 7 and 77, and comparisons made with untreated control
      fish. Despite adverse weather conditions, wide variations in fish weights and
      exposure to new infestations, treatment was effective against chalimus and motile
      stages of L. salmonis. In the autumn trial, efficacy at Day 27 was 89%, and lice
      numbers remained lower on treated fish than on control fish 64 d from the start
      of treatment. In the winter trial, reductions in lice numbers at low temperatures
      were slower but good efficacy was achieved by Day 35. Although control fish had
      to be treated with hydrogen peroxide at Day 21, fish treated only with emamectin
      benzoate on Days 0 to 6 still had 89% fewer lice than control fish at Day 35.
      There were very few C. elongatus present, but at the end of both trials numbers
      were lower on treated fish. No adverse effects were associated with treatment of
      fish with emamectin benzoate.

PMID- 10918984
TI  - Nutrition-toxicology: evolutionary aspects. Introduction. Conference held June
      1999, Coleraine, Northern Ireland.

PMID- 10918983
TI  - Ultrastructure of the microsporidian Inodosporus octospora (Thelohaniidae), a
      parasite of the shrimp Palaemon serratus (Crustacea, Decapoda).
AB  - A parasite of the muscle of the shrimp Palaemon serratus has been examined by
      light and electron microscopy. Development occurs among myofibrils and induces
      ultrastructural alterations of the muscle fibers causing white discoloration.
      This microsporidian is characterized by uninucleate, later diplokaryotic and di
      diplokaryotic meronts. The mother cell develops by rosette-like budding into 8
      uninucleate sporoblasts, each containing 3 tape-like filaments attached to the
      wall that is enclosed in a persistent sporophorous vacuole. Each sporoblast gives
      rise to a uninucleate spore that possesses 3 elongated tape-like filaments
      attached to the spore wall, like spore tails. The morphological characters of the
      spores, redescribed in the present study, suggested that the spores belonged to
      Inodosporous octospora. The possibility that in the future members of Inodosporus
      sp. may be considered a new parasite group is discussed.

PMID- 10918985
TI  - Evolution of antioxidant defence mechanisms.
AB  - The metabolic strengths, weaknesses, opportunities and threats of the metabolic
      ability to split water brought about a proliferation of biological systems,
      produced a toxic oxygenic environment, and were responsible for the development
      of antioxidant defence mechanisms. Evolution is driven by heritable adaptations
      which improve environmental 'fit'. Hence aerobic respiration, using oxygen as a
      nutrient, came to predominate in biological systems, and antioxidant defence
      mechanisms which prevent and neutralise toxic oxygen intermediates have become
      widespread, varied, coordinated and effective. Antioxidant defences are not
      infallible however. In humans, reactive oxygen species-induced damage is
      associated with the ageing process, and with chronic diseases including cancer
      and coronary heart disease. Interestingly, some important antioxidants, including
      ascorbic acid and the tocopherols, cannot be synthesised by humans and must be
      taken in the diet. Another antioxidant, uric acid, is found in much higher
      concentrations in humans than in other mammals, and levels are also affected by
      diet. In humans, therefore, antioxidant defence against toxic oxygen
      intermediates is species specific and heavily influenced by nutrition. In this
      article, the atmospheric and metabolic changes which produced both the threat and
      opportunity offered by an oxygenic environment are outlined. An overview of
      oxygen toxicity, and adaptations to oxidative stress in terms of evolution of
      antioxidant defences, is presented. Finally, suggested benefits underlying our
      curious inability to manufacture ascorbic acid, and the possible role of uric
      acid in human antioxidant defence, are briefly discussed with particular
      reference to nutrition and toxicology.

PMID- 10918986
TI  - Evolutionary events culminating in specific minerals becoming essential for life.
AB  - The environment in which living organisms evolved was apparently a primary
      determinant of which elements became essential for life. The first organic
      materials and, ultimately, life forms most likely were formed in an ancient sea
      containing minerals that provided structural integrity and catalytic ability to
      the first complex organic substances. The site at which life began has been
      suggested to be at the edge of the sea near sediments, or around a hydrothermal
      system. The strongest circumstantial evidence supports a hyperthermophilic
      beginning. Regardless of the site, the biological importance of elements tends to
      parallel oceanic abundance, but in higher forms of life this parallelism
      apparently has been mitigated by a natural selection process that resulted in
      some elements becoming more important because of their superior abilities over
      other elements to perform vital functions. The converse to biological importance
      is that toxicity of elements and oceanic abundance tends to be inversely related.
      The basis for this relationship may be that the efficiency of homeostatic
      mechanisms to cope with a high intake of a specific element probably reflects
      upon the exposure of an organism to the element during its evolution. Thus, a
      study of evolutionary events may be helpful in predicting and comprehending the
      essential and toxic nature of mineral elements in humans.

PMID- 10918987
TI  - Paleolithic vs. modern diets--selected pathophysiological implications.
AB  - The nutritional patterns of Paleolithic humans influenced genetic evolution
      during the time segment within which defining characteristics of contemporary
      humans were selected. Our genome can have changed little since the beginnings of
      agriculture, so, genetically, humans remain Stone Agers--adapted for a
      Paleolithic dietary regimen. Such diets were based chiefly on wild game, fish and
      uncultivated plant foods. They provided abundant protein; a fat profile much
      different from that of affluent Western nations; high fibre; carbohydrate from
      fruits and vegetables (and some honey) but not from cereals, refined sugars and
      dairy products; high levels of micronutrients and probably of phytochemicals as
      well. Differences between contemporary and ancestral diets have many
      pathophysiological implications. This review addresses phytochemicals and cancer;
      calcium, physical exertion, bone mineral density and bone structural geometry;
      dietary protein, potassium, renal acid secretion and urinary calcium loss; and
      finally sarcopenia, adiposity, insulin receptors and insulin resistance. While
      not, yet, a basis for formal recommendations, awareness of Paleolithic
      nutritional patterns should generate novel, testable hypotheses grounded in
      evolutionary theory and it should dispel complacency regarding currently accepted
      nutritional tenets.

PMID- 10918988
TI  - Dietary lean red meat and human evolution.
AB  - Scientific evidence is accumulating that meat itself is not a risk factor for
      Western lifestyle diseases such as cardiovascular disease, but rather the risk
      stems from the excessive fat and particularly saturated fat associated with the
      meat of modern domesticated animals. In our own studies, we have shown evidence
      that diets high in lean red meat can actually lower plasma cholesterol,
      contribute significantly to tissue omega-3 fatty acid and provide a good source
      of iron, zinc and vitamin B12. A study of human and pre-human diet history shows
      that for a period of at least 2 million years the human ancestral line had been
      consuming increasing quantities of meat. During that time, evolutionary selection
      was in action, adapting our genetic make up and hence our physiological features
      to a diet high in lean meat. This meat was wild game meat, low in total and
      saturated fat and relatively rich in polyunsaturated fatty acids (PUFA). The
      evidence presented in this review looks at various lines of study which indicate
      the reliance on meat intake as a major energy source by pre-agricultural humans.
      The distinct fields briefly reviewed include: fossil isotope studies, human gut
      morphology, human encephalisation and energy requirements, optimal foraging
      theory, insulin resistance and studies on hunter-gatherer societies. In
      conclusion, lean meat is a healthy and beneficial component of any well-balanced
      diet as long as it is fat trimmed and consumed as part of a varied diet.

PMID- 10918989
TI  - Recovery of human lymphocytes from oxidative DNA damage; the apparent enhancement
      of DNA repair by carotenoids is probably simply an antioxidant effect.
AB  - BACKGROUND: Many epidemiological studies have identified a protection against
      cancer associated with consumption of fruit and vegetables. One factor in this
      protection may be the enhancement of cellular DNA repair activity by
      micronutrients, such as carotenoids, found in these foods. AIMS OF THE STUDY: To
      measure the capacity of lymphocytes isolated from volunteers supplemented with
      beta-carotene, lutein or lycopene to recover from DNA damage induced in vitro by
      treatment with H2O2. METHODS: Healthy volunteers were given supplements of lutein
      (15 mg/day), lycopene (15 mg/day) and beta-carotene (15 mg/day), each for 1 week,
      the supplementation periods being separated by 3-week wash-out periods. Blood
      samples were taken at the beginning and end of each supplementation, and at 1
      week and 3 weeks during the wash-out period. Carotenoid levels were measured in
      plasma. Lymphocytes were isolated and frozen. Subsequently, they were treated
      with 100 microM H2O2 and incubated for up to 24 h; DNA damage was measured with
      the comet assay (single cell gel electrophoresis) after 0, 2, 4, 8 and 24 h.
      RESULTS: Increases of 2- to 3-fold in mean plasma lutein and beta-carotene
      concentrations were seen at the end of the respective supplementation periods;
      they returned virtually to basal levels after wash-out. Lycopene concentrations
      were less affected by supplementation, and were more variable. H2O2-induced DNA
      strand breaks were apparently only slowly rejoined by the lymphocytes. The
      rejoining of breaks in the first few hours appeared substantially faster in
      lymphocytes following supplementation with beta-carotene, but no such effect was
      seen with lutein. In those individuals who showed increases in lycopene
      concentrations, the recovery was significantly faster. Lymphocytes that were not
      treated with H2O2 showed a transient increase in DNA breakage to about double the
      background level in 2 h, presumably as a result of exposure to atmospheric
      oxygen; this effect, too, was relieved by supplementation with lycopene or beta
      carotene. CONCLUSIONS: While certain carotenoids appear to enhance recovery from
      oxidative damage, this is probably in fact an antioxidant protective effect
      against additional damage induced by atmospheric oxygen, rather than a
      stimulation of DNA repair.

PMID- 10918990
TI  - Improved general health status in an unselected infant population following an
      allergen reduced dietary intervention programme. The ZUFF-study-programme. Part
      I: Study design and 6-month nutritional behaviour.
AB  - BACKGROUND: The best nutritional option for newborn infants is mother's milk.
      However, some newborn babies may not be exclusively breastfed during the first
      months of life, potentially leading to reduced overall health status and the
      early onset of allergic diseases in some infants. Considerable research has been
      devoted to the development and assessment of infant nutrition programmes,
      particularly to the prevention of allergies in high-risk infants. However, equal
      numbers of infants with and without an elevated familial risk of allergies will
      eventually develop allergic diseases. Therefore, optimizing nutritional
      programmes for the early infant population as a whole is an important--but as yet
      insufficiently studied--area of investigation. Moreover, although safe and
      effective nutrition must primarily support healthy development of the infant, few
      studies have evaluated the overall health benefits of nutritional interventions,
      but have focussed on specific allergic manifestations. In animal models, an
      allergen-reduced moderate whey hydrolysate formula (pHF, Nestle Beba HA) induces
      the development of oral tolerance towards cow's milk proteins, without inducing
      sensitization. In infants with a high risk for allergies, pHF formulae reduce the
      early onset of allergic disease during the first 5 years of life by approximately
      50% compared with a dietary regimen of unaltered proteins. At present, very
      little is known about the overall health benefits of such a dietary intervention
      on the unselected infant population as a whole. AIM OF THE STUDY: The aim of our
      prospective, controlled study was to investigate the overall health benefits of
      an allergen-reduced nutritional programme in a newborn infant population
      unselected for atopic risk factors. The population in our study was as comparable
      as possible to the general population of healthy newborn infants. Our study
      included exclusive breastfeeding, use of a moderate whey hydrolysate formula
      (pHF, Nestle Beba HA) if infant formula was needed, and delayed introduction of
      low-allergenic weaning foods. The study included assessments of compliance with
      the dietary programme, and evaluated nutritional habits, growth, and overall
      health status for 24 months. The health evaluation included allergic
      manifestations but did--by porpose--not define or evaluate them specifically.
      Part I of this paper gives results for nutritional habits during the first 6
      months of life, Part II gives results for growth and general health status for
      the same time period, Part III will present feeding habits during the second half
      of the first year of life, and Part IV will present results to 24 months of age.
      The complete study report is published as a supplement to this journal. METHODS:
      Nutritional assignment was to demographically comparable intervention (Z) or
      control (FF) cohorts according to the infant's place of birth. In the
      intervention cohort (Z, n = 564), the recommended dietary regimen was
      breastfeeding and/or the pHF formula, with no weaning food before 4 months of
      age. In the control cohort (FF, n = 566), there was no intervention. Longitudinal
      diet groups, defined for 4 months, excluding dropouts and noncompliants, were
      exclusive breastfeeding (eBF, Z, n = 201, FF, n = 162), partial breastfeeding
      (pBF, Z, n = 222, FF, n = 311), or non-breastfeeding (nBF, Z, n = 43, FF, n =
      62). Imbalances between groups and cohorts in confounding factors that could
      influence health-related symptoms were integrated as covariates into the main
      analyses using logistic regression. Nutritional surveillance was carried out
      using continuous prospective monitoring. RESULTS: The overall rate of
      breastfeeding, irrespective of partial or exclusive breastfeeding or the
      additional use of weaning foods, was similar in both cohorts at 4 and 6 months.
      However, from ages 3 to 6 months, significantly more Z than FF infants were
      exclusively breastfed (p < 0.05), and weaning foods were introduced at a
      significantly later age in Z t

PMID- 10918991
TI  - Lymphocyte proliferation is possible with low concentrations of glycyl-glutamine.
AB  - The positive effect of glutamine on lymphocyte proliferation has previously been
      described. Its dipeptide glycyl-glutamine (GlyGln) is more stable than pure
      glutamine in aqueous solutions. The aim of our study was to investigate the
      relationship between lymphocyte proliferation and varying concentrations of
      glycyl-glutamine in vitro. Isolated human lymphocytes were stimulated with the
      mitogens phytohaemagglutinin (PHA), Concanavalin A (ConA), pokeweed mitogen
      (PWM), and Staphylococcus aureus (SAC). Glycyl-glutamine was added to yield final
      concentrations of 0-2 mmol/l. Overall, minimal concentrations of 0.01 mmol/l
      glycyl-glutamine were sufficient to enhance lymphocyte proliferation over
      baseline (glutamine-free) levels. No difference was found between concentrations
      in the "physiological" range of 0.4 mmol/l and very low concentrations (0.04-0.1
      mmol/l) with SAC, ConA and PWM. Increasing the concentration beyond 0.4 mmol/l
      (up to 2.0 mmol/l) offered further gain with PHA-stimulation only. Lymphocyte
      proliferation under in vitro polyclonal stimulation is maintained even at very
      low concentrations of glycyl-glutamine. Raising the concentration above the
      equivalent of physiological levels does not seem to provide further benefit.

PMID- 10918992
TI  - DNA stability and genomic methylation status in colonocytes isolated from methyl
      donor-deficient rats.
AB  - BACKGROUND: Epidemiological studies report an inverse relationship between intake
      of the B vitamin folic acid and colon cancer. Folate is important for DNA
      synthesis and repair. Moreover, the production of S-adenosylmethionine (SAM),
      essential for normal DNA methylation and gene expression, is dependent on folic
      acid. Folate deficiency may increase the risk of malignant transformation by
      perturbing these pathways. AIMS OF THE STUDY: The principal aim of this study was
      to determine the effects of folate deficiency on DNA stability and DNA
      methylation in rat colonocytes in vivo. As the metabolic pathways of folate and
      other dietary methyl donors are closely linked, the effects of methionine and
      choline deficiency were also evaluated. METHODS: Male Hooded-Lister rats were fed
      a diet deficient in folic acid, or in methionine and choline, or in folate,
      methionine and choline for 10 weeks. DNA strand breakage and misincorporated
      uracil were determined in isolated colonocytes using alkaline single cell gel
      electrophoresis. Global DNA methylation was measured in colonic scrapings. Folate
      was measured in plasma, erythrocyte and liver samples. RESULTS: Methyl donor
      deficiency induced DNA strand breakage in colonocytes isolated from all
      experimental groups. Uracil levels in colonocyte DNA remained unchanged compared
      with controls. DNA methylation was unaffected either by folate and/or methionine
      and choline depletion. Rats fed a folate-deficient diet had less folate in
      plasma, red blood cells and liver than controls. CONCLUSIONS: Folate and methyl
      deficiency in vivo primarily affects DNA stability in isolated colonocytes of
      rats, without affecting overall DNA methylation.

PMID- 10918993
TI  - Chronic vitamin E inadequacy and thermally treated oils affect the synthesis of
      hepatic metallothionein isoforms.
AB  - BACKGROUND: Metallothionein (MT)# synthesis can be stimulated in many organs not
      only by various metals such as cadmium, zinc, and copper, but also by many
      nonmetallic compounds or experimental conditions such as oxidative stress. The
      latter lead to the hypothesis that MT is induced in response to free radicals
      formed in tissues and lipid peroxidation. AIMS OF THE STUDY: Whether the
      relationship between lipid peroxidation and MT synthesis is a common phenomenon
      also valid for lipid peroxidation induced by dietary factors such as chronic
      vitamin E inadequacy and autoxidation products of polyenoic fatty acids derived
      from thermally oxidized oil was investigated in the present study. METHODS: The
      relationship between the induction of metallothionein isoforms I and II (MT-I and
      MT-II) in response to diet-induced lipid peroxidation using a rat model system in
      which lipid peroxidation was examined in vivo by chronic vitamin E inadequacy or
      by administration of lipid peroxidation products from a thermally treated
      polyenoicrich oil with either basal (dietary zinc concentration: 48 mg/kg;
      experiment 1) or Zn-stimulated MT levels (dietary zinc concentration: 305 mg/kg;
      experiment 2) was studied. In both experiments, growing male rats were fed diets
      containing either a fresh or a thermally treated soybean oil with deficient or
      sufficient amounts of vitamin E (14 and 11 vs. 648 and 560 mg alpha-tocopherol
      equivalents per kg diet) over 40 days according to a bifactorial experimental
      design. Plasma and liver concentrations of tocopherols and hepatic levels of
      thiobarbituric acid-reactive substances (TBARS) were measured by high performance
      liquid chromatography. MT isoform concentrations in rat liver were isolated and
      quantified by ion-exchange high performance liquid chromatography and atomic
      absorption spectrometry. RESULTS: Irrespective of the zinc supply, rats receiving
      inadequate amounts of vitamin E with the diet had markedly lower plasma and liver
      concentrations of alpha-tocopherol and total tocopherols than vitamin E
      sufficient rats. ANOVA also revealed an interaction between the diet factors
      vitamin E and oil on tocopherols in plasma and liver of rats from both
      experiments. In experiment 1, where rats received normal amounts of dietary zinc,
      ingestion of the thermally treated oil impaired the tocopherol status compared to
      the treatment with the fresh oil, although this effect was only obvious in the
      vitamin E-deficient groups. In experiment 2, where rats received excessive
      amounts of zinc, the thermally treated oil did not contribute to a reduction of
      the tocopherol status in plasma and liver. In both experiments a significant
      increase in TBARS level, indicative of lipid peroxidation, was observed in the
      liver at chronic vitamin E inadequacy, but no effect of the oil was observed.
      Here, we show that the dietary treatments had some effects on the synthesis of
      liver metallothionein isoforms. In groups, receiving normal amounts of zinc,
      there was a significant interaction between the dietary treatments on the levels
      of MT-I and MT-II in liver. Chronic vitamin E inadequacy which was accompanied by
      diminished tocopherol levels in liver induced the synthesis of MT-I and MT-II.
      When vitamin E inadequacy was combined with the ingestion of a thermally treated
      polyenoic acid-rich oil hepatic levels of MT-I and MT-II remained low. In
      experiment 2, where rats were fed the high zinc diet, vitamin E inadequacy caused
      an increase of hepatic MT-I level just as in experiment 1, although this MT
      stimulating effect was irrespective of the oil. For MT-II there was a 43%
      increase in the vitamin E-deficient group fed the fresh oil compared to all the
      other groups, although this effect was not statistically significant. The liver
      MT isoform response to stress was similar in rats with basal MT levels and Zn
      induced liver MT levels. The failing effect of the thermally treated oil on MT
      levels which were stimulated by vitamin E deficiency in experiment 2 wa

PMID- 10918994
TI  - Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and
      carrier mediated transport mechanism.
AB  - The short-chain fatty acids, acetate, propionate, and butyrate, are the most
      abundant organic anions in the human colon. SCFA play a pivotal role in
      maintaining homeostasis in the colon. Particularly butyrate induces cell
      differentiation and regulates growth and proliferation of colonic mucosal
      epithelial cells, whereas it reduces the growth rate of colorectal cancer cell.
      Previous studies by several groups, including our own, using isolated membrane
      vesicles have demonstrated that the uptake of butyrate is at least in part
      mediated by a non-electrogenic SCFA-/HCO3- antiporter. The purpose of the present
      study was to determine (1) whether Caco-2 cells could serve as an experimental
      model to assess the mechanisms of SCFA transport, and (2) whether monocarboxlate
      transporters could play a role in SCFA transport in these cells. Caco-2 cells
      were found to transport 14C-butyrate in a concentration and time dependent
      manner. The uptake was sodium independent, but was stimulated by lowering
      extracellular pH. The uptake of 500 microM butyrate was reduced by 49.6% +/- 3.3%
      in the presence of propionate and by 57.2% +/- 4.8% in the presence of 10 mM L
      lactate. The addition of 1 mM alpha-cyano-4-hydroxycinnamate and phloretin, both
      known to be potent inhibitors of MCT1, decreased the uptake of 500 microM 14C
      butyrate by 59.4% +/- 4.1% and 48.9% +/- 3.3%, respectively, whereas similar
      concentrations of DIDS did not have any effect. These data suggest that the
      uptake of butyrate in Caco-2 cells occurs via a carrier mediated transport system
      specific for monocarboxylic acids, which is in accordance with characteristics of
      the MCT 1.

PMID- 10918995
TI  - A new bipolar hook for endoscopic surgery.
AB  - This article presents a new bipolar hook for endoscopic surgery. With this
      instrument monopolar and bipolar current can be used. The advantage of this new
      instrument is the possibility of using a bipolar current, which is safer than
      using the monopolar current. The technical details and usage instructions are
      discussed.

PMID- 10918996
TI  - Factors influencing survival in 33 patients undergoing resection of hepatic
      metastases from colorectal cancer.
AB  - BACKGROUND/AIMS: To determine the factors influencing the prognosis of patients
      undergoing resection of hepatic metastases from colorectal cancer. METHODOLOGY:
      Between December 1981 and March 1998, 33 patients underwent potentially curative
      hepatic resection for metastatic colorectal cancer at the Kiryu Kousei General
      Hospital. We retrospectively examined 15 factors, including 3 clinical factors, 5
      primary tumor characteristics and 7 metastatic tumor characteristics. Survival
      rates were estimated by the Kaplan-Meier method, and the weighting of each factor
      was compared by the log-rank test. We used univariate and multivariate analyses
      to assess any associations between the factors and mortality. RESULTS: The 30-day
      operative mortality was 0%. The 5-yr survival rate of the 33 patients was 43%. A
      significant survival advantage was noted in patients with 1 or 2 metastatic
      lesions (25/33, 76%), patients who underwent systematic anatomical resection
      (14/33, 42%) and male patients (16/33, 48%), compared with patients with 3 or
      more lesions (50% and 17%, P = 0.021), patients who underwent non-systematic
      resection (67% and 23%, P = 0.005) and female patients (65% and 20%, P = 0.011),
      respectively. No statistical influence on survival was found in the multivariate
      analysis of these 3 factors. Recurrence was identified in 24 patients (73%) and
      19 of them died of recurrent cancer. CONCLUSIONS: Surgical resection of hepatic
      metastases from colorectal cancer is safe and potentially curative in
      appropriately selected patients.

PMID- 10918997
TI  - Complete remission of the liver metastases of anorectal malignant melanoma with
      regional chemotherapy: a case report.
AB  - The prognosis of anorectal malignant melanoma is very poor. We present a 48-year
      old male patient with anorectal malignant melanoma and multiple liver metastases
      who underwent abdominoperineal resection. A port system was implanted to the
      gastroduodenal artery for regional chemotherapy for liver metastases.
      Histopathological findings of tumor were 5 cm diameter and 2 cm depth, invading
      to the external sphincter. Both regional chemotherapy and immunotherapy were
      initiated 4 weeks postoperatively. The immunochemotherapy regimen included
      cisplatin (via port system) 50 mg/m2 once in 2 weeks, x 8 cycles, alpha
      interferon 5 x 10(6) U subcutaneously on days 1-7 in 4 weeks, x 8 cycles,
      interleukin-2 9 x 10(6) U subcutaneously on days 5-9 in 4 weeks, x 8 cycles.
      Computed tomography scan was taken after the 2nd and 4th cycles of chemotherapy
      and the tumor had not responded to chemotherapy. Dacarbazine 200 mg/m2
      intravenously on days 1-5 in a month, x 4 cycles, was added to the previous
      immunochemotherapy regimen. Computed tomography and magnetic resonance imaging
      scans were taken on the 10th and 12th months after operation, respectively, no
      evidence of metastases in the liver was noted. No case of complete remission of
      liver metastases of anorectal malignant melanoma with regional intraarterial
      chemotherapy and systemic immunochemotherapy has been previously reported in the
      literature.

PMID- 10918998
TI  - Hilar cholangiocarcinoma evaluated by three-dimensional CT cholangiography and
      rotating cine cholangiography.
AB  - BACKGROUND/AIMS: To evaluate the usefulness of three-dimensional cholangiography
      and rotating cine cholangiography in depicting the anatomy of the hilar bile duct
      and tumor extension, and in planning surgical procedures for hilar
      cholangiocarcinomas. METHODOLOGY: Five patients with hilar cholangiocarcinoma and
      obstructive jaundice who underwent percutaneous transhepatic biliary drainage
      followed by resection were serially examined by cine cholangiography and three
      dimensional cholangiography which were reconstructed from a helical computed
      tomography scan. Tumor extension to the bile ducts was prospectively diagnosed
      and the resection margin was planned using both cine and three-dimensional
      cholangiograms. The histological evaluation of the resected specimens were
      compared with preoperative findings of cholangiograms. RESULTS: The three
      dimensional cholangiograms from vertical projection demonstrated the bile duct
      anatomy with excellent image quality. To assess tumor invasion to the
      intrahepatic bile ducts, cine cholangiograms from lateral and oblique projections
      were necessary. Selection of the surgical procedure was influenced by
      preoperative evaluations of the lesion on both three-dimensional and cine
      cholangiograms. Histologically, the resected margin was free from tumor in all
      cases. CONCLUSIONS: Three-dimensional and cine cholangiography allowed accurate
      assessment of the biliary system in patients with hilar cholangiocarcinoma, which
      was helpful for planning the surgical procedure.

PMID- 10918999
TI  - Does cholecystectomy affect antral mucosa? Endoscopic, histopathologic and DNA
      flow cytometric study.
AB  - BACKGROUND/AIMS: Although cholecystectomy is still the "gold standard" for
      treatment of gallstones, this operation may be followed by gastric disorders. The
      aim of this study is to detect the effects of cholecystectomy on gastric antral
      mucosa. METHODOLOGY: This prospective study has been carried out on 46 patients
      (20 M & 26 F) with mean age 41.7 +/- 0.2 years for whom simple cholecystectomy
      for gallstones was decided. Prior to the operation and 1 year after, patients
      were subjected to the following: clinical assessment, upper gastrointestinal
      endoscopy, histopathology of antral mucosa, detection of H. pylori and DNA flow
      cytometry. RESULTS: There was an increase in the number of patients presenting
      suggestive symptoms of reflux gastritis: patients experiencing epigastric pain
      increased from 8 (17.4%) to 11 (23.39%) patients, nausea increased from 6 (13%)
      to 12 (26.1%) patients and bilious vomiting increased from 3 (6.5%) to 11 (23.9%)
      patients. Mild antral gastritis increased from 20 (43.5%) to 27 (58.7%) patients.
      Antral gastritis and antral erosions were detected only after the operation in 8
      (17.4%) and 2 (4.3%) patients, respectively. The incidence of active chronic
      superficial gastritis decreased from 23 (50%) to 13 (28.2%) patients while the
      inactive form increased from 15 (32.6%) to 23 (50%) patients. Chronic atrophic
      gastritis, intestinal metaplasia and dysplasia were only detected postoperatively
      in 2 (4.3%) patients each. There was a decrease in the incidence of H. pylori
      infection from 32 (69.6) to 19 (41.3%) patients. DNA aneuploid pattern increased
      from 1 (2.2%) to 4 (8.7%) patients and there was a significant increase of DNA
      index from 1.01 (+/- 0.03) to 1.03 (+/- 0.05) (P < 0.005). CONCLUSIONS: Changes
      in clinical, endoscopic and histopathologic findings suggest that cholecystectomy
      may affect gastric antral mucosa due to duodenogastric reflux. Flow cytometry may
      be used as an objective method for detection and evaluation of
      postcholecystectomy reflux gastritis.

PMID- 10919000
TI  - Conversion factors in laparoscopic cholecystectomy for acute cholecystitis.
AB  - BACKGROUND/AIMS: Although laparoscopic cholecystectomy already occupies an
      important role in acute cholecystitis, a high rate of conversion continues to be
      referred to in the series published. One of the objectives of this study is to
      assess the preoperative factors that might lead to conversion. METHODOLOGY: 100
      laparoscopic cholecystectomies for acute cholecystitis were studied of which 24
      were converted. Several parameters are taken into consideration: age, sex, ASA,
      echographic data, bacteriological examination of the bile, time elapsing between
      diagnosis and surgery, morbidity and mortality. RESULTS: The analysis made in
      relation to the preoperative, predetermining factors with regards to the
      converted cases provided the following elements in unvaried analysis:
      Preoperative existence of: "plastron" gallbladder (P < 0.002), temperature above
      38 degrees C (P < 0.04), leucocytosis (P < 0.02)), time elapsing between
      diagnosis and surgery (P < 0.005), presence in the echography of pericholecystic
      liquid (P < 0.0005) and edema (P < 0.001); Klebsiella in the gallbladder bile (P
      < 0.005). Age (P = 0.136), sex (P = 0.992), associated diseases (P = 0.961), and
      gallbladder pathology (P = 0.282) did not present statistical differences that
      would prevent valid conclusions. In multi-varied analysis it was only possible to
      consider as independent factors the leucocytosis and the time between diagnosis
      and surgery. CONCLUSIONS: Laparoscopic cholecystectomy is a safe and efficient
      technique in the treatment of acute cholecystitis, which should constitute the
      first choice of treatment for this disease. However, it should be carried out
      within the first 4 days following surgical diagnosis.

PMID- 10919001
TI  - Detection of perfusion areas of the gallbladder vein on computed tomography
      during arterial portography (CTAP)--the background for dual S4a.S5 hepatic
      subsegmentectomy in advanced gallbladder carcinoma.
AB  - BACKGROUND/AIMS: It has been speculated that the veins of the gallbladder join
      the intrahepatic portal veins supplying the Couinaud's S4a-S5. This has been the
      theoretical ground for the resection of these 2 hepatic subsegments in advanced
      gallbladder carcinoma. However, no consensus has been reached on this concept.
      METHODOLOGY: The current study describes the non-neoplastic perfusion defects in
      connection with the gallbladder bed in 100 consecutive hepatic CTAP (computed
      tomographies during arterial portography). The suitability of S4a and S5
      subsegmentectomies of the liver for advanced gallbladder carcinoma was also
      investigated by examining CTAP images of the branches of the portal vein involved
      in the perfusion defect. RESULTS: Two types of gallbladder venous perfusion were
      observed: 1) sphenoid distribution from the gallbladder bed into the P4a (37%),
      P5 (52%) and P6 (3%), and 2) perfusion into the P4 (9%) or directly into the
      middle hepatic vein (9%) after communicating with the hepatic hilum at the dorsal
      side of S4. CONCLUSIONS: These results support liver resection at S4a and S5 as
      the surgical approach for cases of advanced gallbladder carcinoma.

PMID- 10919002
TI  - Asymptomatic adenomyoma of the common hepatic duct discovered during a medical
      checkup: report of a case.
AB  - Although adenomyoma of the gallbladder is not so rare, adenomyoma arising in the
      bile duct is extremely rare. We herein report a case of partial biliary
      obstruction due to adenomyoma of the common hepatic duct. A 64-year-old woman was
      referred to the 1st Department of Surgery, Niigata University School of Medicine
      for surgical intervention, in whom a biliary stricture in the common hepatic duct
      was discovered incidentally during a medical check-up for hyperamylasemia in an
      affiliated hospital. She was asymptomatic without jaundice. Based on her past
      history of abdominal contusion, the insidious presentation and the smooth biliary
      stricture on cholangiography, a diagnosis of benign biliary stricture secondary
      to blunt abdominal trauma was made. A suspicion of malignancy, however, could not
      be ruled out. Subsequently, she underwent a resection of the extrahepatic bile
      duct with lymph node dissection in the hepatoduodenal ligament. The patient's
      postoperative course was uneventful. She was discharged 18 days after the
      operation. Histology of the resected specimen confirmed the diagnosis of
      adenomyoma in the common hepatic duct. Clinicians should note to avoid
      overlooking or misdiagnosing that adenomyoma is a cause of biliary obstruction,
      although extremely rare.

PMID- 10919003
TI  - Amputation neuroma mimics common hepatic duct carcinoma.
AB  - Most amputation neuromas of the biliary tract occur in the cystic duct stump
      after cholecystectomy and are asymptomatic. However, when they arise in the main
      hepatic duct and are associated with obstructive jaundice, it is difficult to
      distinguish them from carcinoma. We describe a case in which preoperative
      differential diagnosis was difficult. A 60-year-old man was admitted to the
      Institute of Clinical Medicine, University of Tsukuba, with a chief complaint of
      jaundice. Cholangiography showed an irregularly elevated nodular lesion on the
      lateral wall of the common hepatic duct and multiple floating stones in the
      choledochus. Ultrasonography and computed tomography revealed one-sided regional
      thickening of the common hepatic duct associated with dilatation of the
      intrahepatic and extrahepatic bile ducts. Carbohydrate antigen 19-9 level was
      markedly elevated to 11,200 IU/mL in the bile juice, but was only 38 IU/mL in the
      serum, below the limit of abnormality. Cholangioscopy showed papillary tumor with
      coarse granular surface mimicking papillary carcinoma, but biopsy revealed no
      malignancy. The patient underwent hepaticocholedochus resection. Although the
      macroscopic finding from the surgical specimens was papillary carcinoma of the
      common hepatic duct penetrating to the hepatoduodenal ligament, histopathological
      examination revealed an amputation neuroma consisting of hypertrophic nerve
      tissues and giant cells containing foreign bodies, probably as a consequence of a
      previous cholecystectomy. The postoperative course was uneventful and the patient
      has been living well for the 5 years since the resection.

PMID- 10919004
TI  - Chemotherapy for bile duct carcinoma in the light of adjuvant chemotherapy to
      surgery.
AB  - Chemotherapeutic regimens that markedly improve survival and quality of life in
      patients with bile duct cancer (cholangiocarcinoma) have not yet been developed.
      Currently, radical resection is the only potentially curative treatment modality
      for these patients. However, complete resection is often impossible and, even
      when achieved, is typically followed by metastasis and/or local recurrence.
      During the past 25 years, patients with cholangiocarcinoma have received
      chemotherapy in an attempt to improve their prognosis; effective methods are
      systemic administration, hepatic arterial infusion, and intraductal infusion. 5
      fluorouracil, adriamycin, mitomycin C, and cisplatin remain the agents used most
      frequently (either singly or in combination) for treating cholangiocarcinoma. In
      particular, 5-fluorouracil has been a component of most chemotherapy regimens for
      bile duct cancer. However, regardless of the administration scheme, results from
      the use of 5-fluorouracil as a single agent have been disappointing. Recent phase
      II (albeit small-population) trials that addressed the biochemical modulation of
      5-fluorouracil in combination with methotrexate, leucovorin, cisplatin,
      interferon, or mitomycin C yielded better results than did a classic (combination
      of 5-fluorouracil, adriamycin, and mitomycin C) FAM regimen. Hepatic arterial
      infusion chemotherapy was associated with the highest response rate and survival
      in patients with localized cholangiocarcinoma (localized in the liver, with no
      extra-hepatic metastasis); however, these results need to be confirmed in large,
      randomized trials. Studies regarding intraductal chemotherapy for patients with
      obstructive jaundice are still in the preliminary stages; therefore, no
      associated benefit could be ascertained. The present review discusses current
      chemotherapy regimens for bile duct cancer and outlines possible future clinical
      investigations.

PMID- 10919005
TI  - Surgical treatment and postoperative outcomes for middle and lower bile duct
      carcinoma in Japan--experience of a single institute.
AB  - BACKGROUND/AIMS: Recently, the Japanese Classification on Cancer of the Biliary
      Tract was revised and adopted the new comprehensive staging that is similar to
      UICC's TNM classification. We should be paying close attention to the
      significance of newly defined extensive factors of carcinomas on the long-term
      prognosis. METHODOLOGY: The surgical outcome for 99 patients who underwent
      resected middle (Bm) and lower (Bi) bile duct carcinomas was reviewed in order to
      evaluate the suitability of the surgical procedures employed for their treatment,
      namely, standard pancreatoduodenectomy for Bi carcinoma and bile duct resection
      with D2 lymph node dissection for Bm carcinoma. RESULTS: The overall 5-year
      cumulative survival rate (operative death excluded) of Bm and Bi carcinoma
      patients was 37.4% and the 5-year survival rate of the patients in whom surgical
      curability (curA) was accomplished was 51.6%. Recently, a new prognostic factor,
      "t-category", which indicates the degree of pericholedochal neoplastic invasion
      was proposed in the 4th edition of the Japanese General Rules for Surgical and
      Pathological Studies on Cancer of the Biliary Tract. The 10-year survival rates
      by t-category were 49.1% (t1), 19.7% (t2), and 0% (t3 and t4) respectively. For
      Bm carcinoma, the patients undergoing bile duct resection under the condition of
      curA showed excellent prognoses. For Bi carcinoma, the patients fulfilling
      particular histological criteria, i.e., those concerning the histological depth
      of neoplastic invasion (m, fm, panc1a), duodenal involvement (du0, du1), vascular
      invasion (pv0), pericholedochal neoplastic invasion (t1), lymph node metastasis
      (n0), and comprehensive stage I, had good postoperative outcomes. Taking into
      account the fact that the metastatic rate of paragastric lymph nodes was 1.3%,
      the cases of panc0,1 should be operated by pylorus-preserving
      pancreatoduodenectomy. The overall 5-year survival rates including far-advanced
      cases were 39.9% in Bm carcinoma patients and 36.9% in Bi carcinoma patients.
      However, these postoperative outcomes are far from satisfactory. CONCLUSIONS:
      Therefore, we concluded that pancreatoduodenectomy and pylorus-preserving
      pancreatoduodenectomy with extended D3 lymphadenectomy combined with systematic
      multimodal therapy are indicated in each and every case of Bm and Bi carcinoma.

PMID- 10919006
TI  - Genomic alterations in primary gastric cancers analyzed by comparative genomic
      hybridization and clinicopathological factors.
AB  - BACKGROUND/AIMS: Genetic changes during the oncogenesis and progression of
      gastric cancer remain unclear. The aim of our study was to analyze chromosomal
      aberrations in primary gastric cancers. METHODOLOGY: Using comparative genomic
      hybridization, we screened 47 primary gastric cancers for changes in the number
      of copies of DNA sequences. RESULTS: Gains of chromosome arms 20q (55%), 20p
      (36%), 17q (32%), 19q (30%) and 16p (30%), and losses of chromosome arms 4q
      (40%), 17p (40%), 5q (38%), 18q (30%) and 4p (28%) were detected most frequently.
      In addition, a high level of amplification was observed at 3q21 (2%), 6p21 (4%),
      7q31 (6%), 8q23-24 (2%), 19q12-13 (2%), and 20q13 (2%). Among these alterations,
      the gain of 20q was the most frequent change. We then compared these changes with
      clinicopathological factors and identified signet ring cell carcinomas in 6
      cases. Our study demonstrated no amplification of chromosome 20q in signet ring
      cell carcinoma in contrast to that in the other histologic types of gastric
      cancer. CONCLUSIONS: Our findings may be related to the morphologic and clinical
      features of signet ring cell carcinoma, and several oncogenes mapped on 20q may
      play an important role as determinants of the clinical and histologic features of
      gastric cancer.

PMID- 10919007
TI  - Hepatocellular carcinoma in Mansoura-Egypt: experience of 385 patients at a
      single center.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma is one of the commonest malignancies in
      the world. The two main etiological factors for hepatocellular carcinoma are
      cirrhosis and viral hepatitis. Although the first choice of treatment for
      hepatocellular carcinoma is surgical resection, most of them are unresectable at
      the time of diagnosis. METHODOLOGY: From January 1994 to June 1999, 385 patients
      with hepatocellular carcinoma were presented to the Gastroenterology surgical
      center, Mansoura University, Egypt and subjected to similar diagnostic process.
      Forty-five (11.6%) of these patients (34 males and 13 females) with a mean age of
      50.9 years (+/- 7.53 years) were subjected to different types of hepatic
      resection. RESULTS: The underlying liver pathology was cirrhosis in 85%. Positive
      virology was found in 82.5% (HCV 61%, HBV 14.5% and combined 7%). The main
      presentation were asymptomatic in 144 (37.4%) patients, abdominal pain in 92
      (23.9%) patients, ascites in 95 (24.6%) patients, jaundice in 53 (14%) patients
      and upper gastrointestinal hemorrhage in 26 (6.75%) patients. Only 45 (11.6%)
      were resectable, they were subjected to hepatic resection with operative
      mortality in 2 cases (4.4%) and with overall mortality in 29 (64.4%) cases after
      48 months (32.8 +/- 19 months) of follow-up. The main causes of late mortality
      were recurrence in 14 (31.1%) cases, hepatic cell failure in 7 (15.5%) cases and
      other causes in 6 (13.3%). CONCLUSIONS: Hepatocellular carcinoma is now a common
      malignancy in Egypt, which usually develops on top of cirrhosis of viral origin
      in 82%. Hepatic resection is the only method of treatment with a low
      resectability rate.

PMID- 10919008
TI  - Three-dimensional reconstruction of colorectal tumors from serial tissue sections
      by computer graphics: a preliminary study.
AB  - BACKGROUND/AIMS: We present herein the three-dimensional reconstruction of
      colorectal tumors, with particular reference to growth pattern into each layer of
      the colorectal wall, and measurement of tumor volume and surface area.
      METHODOLOGY: Conventional tissue section images of colorectal tumors were
      analyzed using a computer graphics analysis program. The two-dimensional extent
      of invasion by each tumor into each layer of intestinal wall were determined from
      the images of each section. Based on data from multiple sections, tumor and
      surrounding normal tissue layers were reconstructed three-dimensionally, and
      volume and surface area of the tumors were determined. RESULTS: Using this
      technique, three-dimensional morphology of tumor and tumor progression into
      colorectal wall could be determined. Volume and surface area of the colon tumor
      were 4871 mm3 and 1741 mm2, respectively. Volume and surface area of the rectal
      tumor were 1090 mm3 and 877 mm2, respectively. CONCLUSIONS: This technique may
      provide a new approach for pathological analysis of colorectal carcinoma.

PMID- 10919009
TI  - Assessment of portosystemic shunt by summation of radioactivity during
      201thallium chloride portal scintigraphy in patients with chronic liver disease.
AB  - BACKGROUND/AIMS: Portal scintigraphy is a useful non-invasive method for the
      determination of portosystemic shunts in patients with liver cirrhosis. Several
      procedures have been reported for its execution in clinical practice but most of
      them failed to show sufficient sensitivity for the diagnosis of portosystemic
      shunt. In the present study, we evaluated whether summation of radioisotope
      counts obtained during intrarectal or intraduodenal administration of 201thalium
      chloride is useful for increasing the diagnostic yield of porto-systemic shunts
      in patients with chronic liver disease. METHODOLOGY: Seven patients with chronic
      viral hepatitis and 8 with liver cirrhosis secondary to viral hepatitis were
      enrolled in this study. Following the conventional protocol, 201thalium chloride
      was administered per rectum and the 60-second-heart-to-liver uptake (conv-H/L-R)
      ratio was calculated after 20 min. Continuous measurement of the radioactivity
      signals during 20 min were also done and the summated heart-to-liver uptake (sum
      H/L-R) ratio from the total radioactivity count were calculated. Measurement of
      the conventional heart-to-liver uptake (conv-H/L-D) ratio and the summated (sum
      H/L-D) ratio were also done as described above after the intraduodenal
      administration of 201thalium chloride by endoscopy. RESULTS: All ratios (conv-H/L
      R, conv-H/L-D, sum-H/D-R, sum-H/L-D) were significantly higher in patients with
      liver cirrhosis than in those with chronic hepatitis. Among all heart/liver
      ratios, only the sum-H/L-R ratio was significantly different between patients
      with and without esophageal varices. Serum hyaluronate level and other liver
      function tests were found to be significantly correlated with all heart-to-liver
      ratios, but they were more strongly correlated with the sum-H/D-R and sum-H/L-D
      ratios than with the conv-H/L-R and conv-H/L-D ratios. CONCLUSIONS: The results
      of this study showed that the heart-to-liver ratio calculated by summation of
      radioactivity is better than the conventional method for the diagnosis of
      portosystemic shunt in patients with chronic liver disease.

PMID- 10919010
TI  - The treatment of portal hypertension by videolaparoscopy in situs inversus
      totalis.
AB  - A rare case of a 32-year-old male with situs inversus totalis viscerum admitted
      to hospital for hematemesis owing to portal hypertension of Laennec cirrhosis was
      treated for the first time by videolaparoscopic surgery. Situs inversus diagnosis
      was confirmed by thoracic radiography, electrocardiogram, echocardiogram,
      abdominal echography and computed tomography. Upper gastrointestinal endoscopy
      showed esophageal varices and large varices in the fundus of the stomach. A
      successful operation (azygo-portal disconnection, splenic artery ligation without
      splenectomy; transesophageal suturing of esophageal varices without opening the
      esophagus and cholecystectomy), was performed by videolaparoscopy. The uneventful
      postoperative evolution (4-day hospitalization) reinforces the viability of the
      videolaparoscopic approach and the possibility of the application of this
      procedure even to situs inversus totalis organorum.

PMID- 10919011
TI  - Colonic metastasis of breast carcinoma.
AB  - Metastasis of breast carcinoma to the colon is a rare occurrence. We report here
      the case of a 65-year-old patient who presented a stenosing tumor of breast
      origin, located in the right colon. Some of the regional lymph nodes were
      infiltrated but no distant metastasis were detected. The primary breast lesion
      was a 4-cm infiltrating adenocarcinoma, operated 4 years earlier. Surgical
      removal of the lesion was followed by Endoxan-Epirubicin and 5-Fluororacil
      chemotherapy and the patient remained disease-free during the 3 years of follow
      up. We could find only 2 similar cases reported in the world literature until
      now. Profound anemia in a patient with a past history of breast carcinoma may
      indicate colonic metastasis; treatment should be surgery followed by
      chemotherapy.

PMID- 10919012
TI  - Laparoscopic colectomy: indications, standardized technique and results after 6
      years experience.
AB  - BACKGROUND/AIMS: The aim of the present study was to perform a retrospective
      study of our experience in performing laparoscopic colon surgery after 6 years
      experience. METHODOLOGY: From April 1992 to April 1998, 215 patients underwent
      colon laparoscopic surgery. There were 121 females and 94 males, whose average
      age was 66.7 (range: 31-92). RESULTS: 170 laparoscopic procedures were completed
      out of 215 (79%): 151 resections (22 for a benign lesion and 129 for a malignant
      one), 4 reversal of Hartmann's procedures, 6 rectopexy, 3 ileotransverstomies and
      6 suture of traumatic colon perforation. There were 3 mortalities out of 215
      (1.9%). The conversions were 45 out of 215 (20.9%); 22 (10.2%) cases were,
      however, converted to a laparoscopic facilitated procedure. The most common
      causes for conversion were the presence of bulky tumors and/or tumors that
      contaminated the adjacent structures (16/215), adhesions due to previous
      operations (9/215) and the patient's obesity (8/215). There were 39 complications
      (18.1%), 10 (4.6%) out of which required reoperation (2 anastomotic fistula, 2
      anastomotic leak, 2 anastomotic stenosis, 2 hemorrhage, 1 colic iatrogenic
      perforation and 1 occlusion to rotation of anastomosis). There were only 2
      recurrences (1.3%), 15 months (C2) and 8 months (B2) after the operation for
      intraoperative technical error. The average number of lymph nodes harvested in
      resected specimens was 12.8 (range: 1-41), whereas the mean distance of the tumor
      from the proximal margin of resection was 11.5 cm (range: 5-35), and from the
      distal margin 7.5 cm (range: 1-25). The average operative time was 165 min
      (range: 40-360), and the mean hospital stay was 9.2 days (range: 6-40).
      CONCLUSIONS: A colon resection for a malignant lesion, if performed with the
      highest respect for the oncologic principles, proves that it is impossible to
      develop a wall and intraluminal recurrence, which, in our opinion, may be caused
      by an improper surgical technique. Therefore, neoplastic colon laparoscopic
      surgery must be the perogative of a few selected and specialized centers.

PMID- 10919013
TI  - Role of nitric oxide in the left-sided colon of patients with diverticular
      disease.
AB  - BACKGROUND/AIMS: Non-adrenergic non-cholinergic inhibitory nerves are the most
      important nerves in the enteric nervous system of the human gut. Recently, it has
      been established that nitric oxide is released by stimulation of non-adrenergic
      non-cholinergic inhibitory nerves. Therefore, in order to evaluate the function
      of nitric oxide in the left-sided colon of patients with diverticular disease, we
      examined the enteric nerve responses in colonic tissues from patients with this
      disease, and also used the left-sided normal colon as a control. METHODOLOGY:
      Colonic tissue specimens (the diverticular bearing segments) were obtained from 9
      patients with diverticular disease of the left-sided colon, and normal segments
      of the left-sided colon were obtained from 16 patients with ascending colon
      cancer. A mechanograph was used to evaluate in vitro colonic responses to
      electrical field stimulation of adrenergic and cholinergic nerve before and after
      treatments with various autonomic nerve blockers, NG-nitro-L-arginine, and L
      arginine. RESULTS: 1) The diverticular colon was more strongly innervated by
      cholinergic nerves than the normal colon (P < 0.01); 2) Non-adrenergic non
      cholinergic inhibitory nerves were found to act on the normal colon and to a
      lesser extent in the diverticular colon (P < 0.05). 3) Nitric oxide mediates the
      relaxation reaction of non-adrenergic non-cholinergic inhibitory nerves in the
      normal colon and to a lesser extent in the diverticular colon. CONCLUSIONS: These
      findings suggest that the intrinsic intestinal innervation contains excitatory
      and inhibitory nerves and that the former, especially cholinergic nerves, are
      dominant in the left-sided colon with diverticula. In addition, diminution of
      action of non-adrenergic non-cholinergic inhibitory nerves by substances such as
      nitric oxide may be largely related to the high intraluminal pressure by colonic
      segmentation observed in the left-sided colon with diverticula.

PMID- 10919015
TI  - Colorectal carcinoma in Ibadan, Nigeria: a 20-year survey--1971 to 1990.
AB  - BACKGROUND/AIMS: Five hundred and four (504) cases of histologically proven
      adenocarcinoma of the large bowel were seen in the University College Hospital,
      Ibadan, between 1971 and 1990. The rise in incidence predicted by the writers in
      the seventies is confirmed but it is feared that the economic depression may make
      alternative medicine attractive and turn patients away from the hospitals. The
      sex ratio has approached that seen in the West but the average age incidence has
      not changed. METHODOLOGY: One hundred and forty-one (141) case notes were
      available for critical evaluation. RESULTS: These case notes show that patients
      still present rather late and some still find the idea of terminal colostomy
      sufficiently repugnant to refuse surgery. This disease is no respecter of persons
      and the clinical features are in no way different from those already recorded.
      Most of the colonic tumors are located on the right side of the colon. This has
      been the pattern in the African population--a phenomenon now reported frequently
      in the West. CONCLUSIONS: The colon/rectum ratio has been reversed in favor of
      the rectum but unfortunately, this has not had a positive influence in early
      presentation and diagnosis. The "silent majority" on the right side of the colon
      can only add to the problem of late presentation. A plea is, therefore, made for
      adeq-uate investigations of 40 years old and above presenting with vague pain in
      the right iliac fossa and/or features of hemorrhoids which may herald carcinoma
      on the right and left, respectively.

PMID- 10919014
TI  - Laparoscopic colonic resections versus open surgery: a prospective non-randomized
      study on 310 unselected cases.
AB  - BACKGROUND/AIMS: Laparoscopic colorectal surgery, particularly for malignancy, is
      still debated. The aim of this study was to prospectively evaluate the
      postoperative outcome as well as the short- and medium-term results of
      laparoscopic surgery compared with those after open conventional surgery.
      METHODOLOGY: A series of 310 consecutive patients, operated on by the same
      surgical team, have been included in this study; 150 patients (75% with malignant
      lesions) underwent laparoscopic surgery, whereas 160 patients (73% with malignant
      lesions) were treated by open surgery. The treatment modality was selected by the
      patients after reading the informed consent form. RESULTS: Laparoscopic surgery
      was technically feasible in 91.4% of cases. Mean operative time for laparoscopic
      surgery was longer than for open surgery (251 vs. 175 min) (P < 0.001). Mean
      postoperative hospital stay after laparoscopic surgery was 10.5 days, as compared
      to 13.3 days after open surgery (P < 0.05). In the laparoscopic surgery group
      minor complications' rate was 3.6% and compared favorably to the 7.5% observed
      after open surgery (P = 0.261). No statistically significant difference was
      observed in the major complications rate (9.4% after laparoscopic surgery and
      6.8% after open surgery) and in operative mortality (1.4% for laparoscopic
      surgery and 0.6% for open surgery). The local recurrence rate was lower after
      laparoscopic surgery as compared to open surgery: 3% versus 9.2% (P = 0.152),
      respectively. Mean follow-up was 34.2 months during which time we observed 2
      cases of port site recurrence. After implementing adequate prophylactic measures,
      no parietal implants were observed in the last 80 patients who underwent
      laparoscopic surgery for malignancy. Distant site metastases occurred in 11% in
      both groups. At 36 months cumulative survival probability in laparoscopic surgery
      completed malignant cases was 0.74% as compared to 0.66% after open surgery.
      CONCLUSIONS: Morbidity and mortality were similar in the 2 groups. Laparoscopic
      patients experienced less pain. A slightly higher incidence of local recurrence
      was observed in the open surgery group, whereas the percentage of distant site
      metastases and the cumulative survival probability in the 2 groups were similar.
      Port site recurrences are a cause of concern but they can be prevented with
      adequate prophylactic measures. The short- and medium-term results of
      laparoscopic surgery compared favorably with those of open surgery in this
      prospective non-randomized study. Long-term oncological result are not known yet.
      In patients with malignancy prospective randomized trials on larger patient
      numbers are required.

PMID- 10919016
TI  - Interleukin-13 inhibits nitric oxide production in human colonic mucosa.
AB  - BACKGROUND/AIMS: Nitric oxide synthesis is increased in rectal biopsies from
      patients with ulcerative colitis and colonic epithelial cells are considered to
      be a major source of nitric oxide in intestinal inflammation. METHODOLOGY: Human
      colonic biopsies from normal bowel mucosa and colonic epithelial cell line HT-29
      were cultured in the presence of the inflammatory cytokines IL-1 alpha + TNF
      alpha + IFN-alpha added after 1 hour pretreatment with vehicle or Interleukin-13.
      Nitrite levels were determined at 30 hours in culture supernatants by a
      fluorometric assay. RESULTS: Unstimulated human colonic biopsies and HT-29 cells
      produced a basal amount of nitrite. Stimulation with IL-1 alpha + TNF-alpha + IFN
      alpha induced a significant (P < 0.001) increase of nitrite generation by both
      human colonic biopsies and HT-29 cells. The presence of Interleukin-13 produced a
      significant (P < 0.001) suppression of the cytokine-induced nitrite generation
      from both colonic biopsies and HT-29 cells. CONCLUSIONS: Nitric oxide generation
      in human colonic mucosa is susceptible to manipulation by proinflammatory
      cytokines. Interleukin-13 has an inhibitory effect on cytokine induced nitrite
      production in colonic mucosa and could play an anti-inflammatory role in
      intestinal inflammation.

PMID- 10919017
TI  - Colonic varices ruptured via drainage catheter after extended right hepatectomy.
AB  - Extended right hepatectomy was performed on a 69-year-old woman with bile duct
      carcinoma of the hepatic hilum. Three weeks after the operation, an abscess was
      detected at the resected surface and a drainage catheter was inserted. The
      patient was discharged with the drainage catheter in place and followed-up at a
      local hospital. Three months later, the drainage catheter was removed. Bleeding
      immediately occurred through the fistula, and fistulography revealed varices.
      Angiography demonstrated right colonic varices, and the fistula was embolized
      with coils. There was no further bleeding. In conclusion, colonic varices that
      ruptured via a fistula of a drainage catheter were embolized through the fistula.
      Embolization of the fistula was useful in stopping the bleeding.

PMID- 10919018
TI  - Long-term results of modified distal splenorenal shunts for the treatment of
      esophageal varices.
AB  - BACKGROUND/AIMS: Long-term results were compared for 3 types of distal
      splenorenal shunt for the treatment of esophageal varices. METHODOLOGY: Between
      July 1983 and December 1997, 45 patients with esophageal varices underwent distal
      splenorenal shunt. Group 1 underwent standard distal splenorenal shunt (n = 11).
      Group 2 underwent distal splenorenal shunt with splenopancreatic disconnection (n
      = 11). Group 3 underwent distal splenorenal shunt with splenopancreatic
      disconnection and gastric transection (n = 23). RESULTS: Additional treatment for
      recurrent varices was required in group 1, (n = 1, 9.1%), group 2 (n = 2, 18.2%),
      and group 3 (n = 1, 4.3%). All of the patients with recurrent varices developed a
      shunt stenosis within the 1st year after distal splenorenal shunt. The prevalence
      of hyperammonemia in group 1 was 40.0% at 1, 5, and 10 years. In group 2, the
      prevalence was 14.3% at 1 year, 31.4% at 5 years, and 54.3% at 10 years. In group
      3, the prevalence was 0% at 1 year, and 9.1% at 5 and 10 years. The differences
      between group 3 and groups 1 and 2 were significant (P < 0.01). The cumulative
      survival rates at 1 year were 90.9%, 63.6%, and 95.7% for groups 1, 2, and 3,
      respectively. At 10 years, the cumulative survivals rates were 70.7%, 63.6%, and
      69.4% for groups 1, 2, and 3, respectively. There were no significant differences
      in survival between the 3 groups. CONCLUSIONS: Distal splenorenal shunt with
      splenopancreatic disconnection and gastric transection may reduce the incidence
      of postoperative hyperammonemia.

PMID- 10919019
TI  - Expandable metal stents versus laser combined with radiotherapy for palliation of
      unresectable esophageal cancer: a prospective randomized trial.
AB  - BACKGROUND/AIMS: Because of the short life expectancy of patients with esophageal
      cancer, relief of dysphagia associated with low morbidity and mortality must be
      the aim of any therapeutic strategy. METHODOLOGY: A total of 39 patients with
      unresectable esophageal cancer were randomly allocated to either receive combined
      laser-percutaneous radiotherapy (group 1, n = 21) or to have a self-expanding
      metal stent placed (group 2, n = 18). Some patients in group 2 required initial
      laser therapy (group 2a, n = 8). Treatment efficacy was evaluated on the basis of
      improved dysphagia, restenosis, hospital stay, survival time and costs. RESULTS:
      Both treatments were able to significantly improve dysphagia. Restenosis occurred
      in 43% of group 1 and 22% of group 2 patients. In group 1, 2 patients had severe
      bleeding episodes and 2 patients developed esophago-tracheal fistulas. One group
      1 patient died due to uncontrollable bleeding and 1 patient to recurrent
      aspiration. No treatment-related death was observed in group 2. Hospital stay was
      30.0 (mean: 5.4) days in group 1, 18.9 (mean: 4.2) days in group 2a and 7.1
      (mean: 3.1) days in group 2b. There was no statistical difference between the 3
      groups with regard to survival. Costs were highest in group 1 and lowest in group
      2b. CONCLUSIONS: The treatment of unresectable esophageal cancer with self
      expanding metal stents appears to be simple, safe, as good as laser combined with
      radiotherapy and cost efficient.

PMID- 10919020
TI  - Prognostic significance of the carcinoma area in the thickest part of the lymph
      node.
AB  - BACKGROUND/AIMS: The carcinoma volume in each metastatic lymph node varies
      widely. Our aim was to define the meaning of carcinoma volume in lymph nodes as a
      prognostic factor. METHODOLOGY: One hundred and five patients with preoperatively
      untreated esophageal carcinoma who underwent surgery were enrolled as subjects.
      In the present study, the carcinoma area within lymph nodes at their thickest
      level was substituted for carcinoma volume in lymph nodes for measurement and
      analysis. A total of 3,703 lymph nodes were isolated and the area of the
      carcinoma in the thickest part of the lymph node (CALN) was measured. Univariate
      and multivariate analysis of prognostic significance were made for the factors
      age, sex, cancer location, cell differentiation, pT, conventional classification
      of lymph nodes for surgical dissection (n), number of metastatic lymph nodes (MLN
      number), and CALN. RESULTS: In all 105 cases, n was the best prognostic factor
      and CALN was more useful than MLN number. In the cases in which absolute curative
      resection was successful, CALN was the best prognostic factor. CONCLUSIONS: The
      carcinoma area in the thickest part of the lymph node is a meaningful prognostic
      factor.

PMID- 10919021
TI  - Endoscopic injection sclerotherapy with ligation versus endoscopic injection
      sclerotherapy alone in the management of esophageal varices: a prospective
      randomized trial.
AB  - BACKGROUND/AIMS: Endoscopic injection sclerotherapy with ligation is a technique
      by which endoscopic injection sclerotherapy is first carried out for a target
      esophageal varix using an endoscope equipped with a device for endoscopic
      variceal ligation, and subsequently, endoscopic variceal ligation is performed
      for the varix together with the injection site of the sclerosing agent. The aim
      of this prospective, randomized trial was to compare endoscopic injection
      sclerotherapy with ligation with endoscopic injection sclerotherapy techniques in
      utility for patients with esophageal varices. METHODOLOGY: Twenty-four patients
      with esophageal varices who were to undergo either an elective treatment of
      bleeding esophageal varices or a prophylactic treatment of non-bleeding
      esophageal varices underwent endoscopic injection sclerotherapy with ligation (n
      = 12) or without ligation (n = 12). The patients were followed for a mean of 19.9
      +/- 8.1 months in the endoscopic injection sclerotherapy with ligation (EISL)
      group and 19.5 +/- 5.4 months in the Endoscopic injection sclerotherapy (EIS)
      group. RESULTS: The red color sign disappeared in 10 patients in the EISL group
      and 3 in the EIS group (P = 0.004) after initial treatment. The length of time
      required for initial treatment was 16.3 +/- 4.7 min for the EISL group and 27.2
      +/- 6.2 min for the EIS group (P = 0.0003). For treatment-related complications,
      no significant difference was noted between the 2 groups and no serious
      complication were noted in the 2 groups. The total quantity of ethanolamine
      oleate used to attain the endpoint was 17.3 +/- 7.9 mL for the EISL group and
      25.2 +/- 9.7 mL for the EIS group (P < 0.05). The cumulative non-relapse rate for
      2 years following attainment of the endpoint [F1, RC(-)] was 81.5% for the EISL
      group and 47.5% for the EIS group, producing no significant difference between
      the 2 groups. The cumulative non-bleeding and survival rates were 100% in the 2
      groups. CONCLUSIONS: Endoscopic injection sclerotherapy with ligation is more
      useful for esophageal varices than endoscopic injection sclerotherapy alone.

PMID- 10919022
TI  - Estimation of the enterogastric reflux by modified scintigraphic method.
AB  - BACKGROUND/AIMS: The aim of the study was to introduce the chosen and modified
      model of the nuclear medicine method for the detection and quantification of
      enterogastric reflux, as well as evaluation of its clinical validity.
      METHODOLOGY: The study was performed in 172 patients: with gastric and duodenal
      ulcer, after Billroth I and Billroth II gastrectomy, with gastroesophageal
      reflux, after cholecystectomy, with chronic cholecystitis and chronic duodenal
      disease. Acquisition was performed with a gamma camera, during 90 min after
      intravenous application of 185MBq 99mTc-Dietil IDA. Test meal was given in the
      30th minute, while the gastric region was marked at the end of the study. On the
      basis of the radioactivity changes in the regions of the stomach and
      hepatobiliary system, the presence of enterogastric reflux was determined and its
      index calculated. RESULTS: In all the groups of patients, values were
      significantly higher than in the controls (P < 0.05). The most frequent
      occurrence and the largest quantity of reflux was present in patients after
      Billroth II gastrectomy with significantly different values from other groups of
      patients (P < 0.05). CONCLUSIONS: The obtained results approve clinical value of
      the chosen and modified scintigraphy of enterogastric reflux, as a non-invasive
      and physiological method, which provides exact data about its presence and
      quantity.

PMID- 10919023
TI  - Expression of thymidylate synthase in human gastric and colorectal
      adenocarcinomas is upregulated by p16/INK4.
AB  - BACKGROUND/AIMS: We observed the relationship between the expression of
      thymidylate synthase protein (pTS) and cell cycle regulators in gastric and
      colorectal adenocarcinoma tissues. METHODOLOGY: This study included 80 gastric
      and 50 colorectal adenocarcinomas. Immunohistochemical staining was performed
      using a polyclonal antibody to recombinant human pTS, and monoclonal antibodies
      to p53, p21/WAF1CIP1, p16/INK4, cyclin D1 and pRB. Each staining was quantified
      using computerized image analysis on a CAS 200 system. We selected the mean
      expression values as the cutoff values to distinguish between high and low
      expression of these substances. RESULTS: There was no relationship between pTS
      expression and p21/WAF1CIP1, cyclin D1, or pRB expression in gastric and
      colorectal carcinomas. In both gastric and colorectal carcinomas, the pTS
      expression was significantly low in the high p16/INK4 expression subgroup
      compared with the low p16/INK4 expression subgroup (P < 0.05). Further, the pTS
      expression was significantly high in the high p53 expression subgroup compared
      with the low p53 expression subgroup in colorectal adenocarcinomas (P < 0.05).
      CONCLUSIONS: pTS expression regulation in human gastric and colorectal
      adenocarcinomas in complex, and upregulated by p16/INK4.

PMID- 10919024
TI  - Limited influence of pouch function on quality of life after ileal pouch-anal
      anastomosis.
AB  - BACKGROUND/AIMS: Despite a high frequency of pouch function disorders, most
      patients are satisfied with the outcome of ileo-anal pouch surgery. Aims of this
      study were: 1) To assess the influence of pouch function on quality of life and,
      2) to determine which aspects of pouch dysfunction affect quality of life the
      most. METHODOLOGY: Questionnaires, addressing current pouch function and quality
      of life (Rand-36, GIQLI), were sent to all (53) patients with intact ileo-anal
      pouches, operated on between 1987 and 1997 in our center. RESULTS: Thirty-six of
      53 patients responded. Compared to reference data, Rand-36 scores for role
      limitations based on a physical problem, vitality and general health perception
      were significantly diminished (P < 0.01). Physical and social functioning were
      normal. The GIQLI score was slightly decreased (111.7 vs. 125.8, P < 0.01).
      Overall pouch function did not correlate with the overall Rand-36 score, but
      correlated well with the overall GIQLI score (r = -0.47). Both quality of life
      scores were diminished mainly by the night-time stool frequency. CONCLUSIONS: 1)
      Quality of life after IPAA, as measured with validated questionnaires, is only
      slightly decreased; 2) the GIQLI questionnaire is more sensitive to pouch
      dysfunction than the Rand-36; 3) night-time stool frequency influences quality of
      life the most.

PMID- 10919025
TI  - Surgical presentation of abdominal tuberculosis: a protean disease.
AB  - BACKGROUND/AIMS: The incidence of tuberculosis is rising again in the Western
      world, due to the emergence of new groups of patients at risk. This paper intends
      to describe the various patterns of surgical presentation of abdominal
      tuberculosis in an industrialized country. METHODOLOGY: A retrospective study was
      made of all patients admitted to our surgical institution, and in whom a
      diagnosis of abdominal tuberculosis was established. Eleven patients were
      identified. Ten of them were migrants from countries endemic for tuberculosis.
      RESULTS: Six patients presented with acute abdominal pain (3 in right lower
      quadrant) and had surgery in emergency. Two patients had elective surgery for
      diagnostic purposes. Two patients underwent other invasive diagnostic and/or
      therapeutic procedures. One patient was treated conservatively. Unusual
      presentations included 2 patients with periportal lymphadenitis and compressive
      features on the main bile duct and/or the portal vein, and 1 patient with acute
      duodenal tuberculous perforation. The main localization of disease was lymph
      nodes for 5 patients, intestinal for 4 and peritoneal for 2. CONCLUSIONS:
      Surgeons must be aware of the wide clinical spectrum of abdominal tuberculosis
      and have a high index of suspicion when confronted with patients from an endemic
      area and presenting with unclear abdominal symptoms.

PMID- 10919026
TI  - Jejunal pouch interposition with an antiperistaltic conduit as a pyloric ring
      substitute after standard distal gastrectomy: a comparison with the use of an
      isoperistaltic conduit.
AB  - BACKGROUND/AIMS: We performed jejunal pouch interposition with a short
      antiperistaltic conduit as a pylorus substitute after gastrectomy for gastric
      cancer and compared the outcome with an isoperistaltic conduit. METHODOLOGY:
      After a standard distal gastrectomy and lymph node dissection, a 15-cm-long pouch
      was formed using 3 linear staples (Endo-GIA) and interposed between the residual
      stomach and duodenum. The distal jejunal limb was made into a 3-cm-long
      isoperistaltic conduit in the isoperistaltic group (n = 17), and the proximal
      jejunal limb was made into a 3-cm-long antiperistaltic conduit in the
      antiperistaltic group (n = 8). Postoperatively, the patients were interviewed
      periodically to document any complaints. A dual-phase, dual-isotope radionuclide
      gastro-pouch-emptying study was performed 1 and 6 months after surgery. RESULTS:
      None of the patients developed postoperative complications and showed discomforts
      of dumping, stasis or reflux esophagitis. The dietary volume and body weight of
      patients gradually increased in both groups after 6 months. The combined
      radioisotope retention rate for the pouch and residual stomach was 31% for liquid
      food and 35% for solid food in the isoperistaltic group after 120 min, and 41%
      and 57%, respectively, in the antiperistaltic group. The pattern and emptying
      rate for solid food in the antiperistaltic group were more similar to those in
      healthy individuals than in the isoperistaltic group. CONCLUSIONS: The gastro
      pouch-emptying test in the antiperistaltic group demonstrated acceptable emptying
      for a pyloric ring substitute. A reasonably good quality of life has been
      obtained for patients having an antiperistaltic jejunal conduit.

PMID- 10919027
TI  - A catastrophic complication of systemic lupus erythematosus: massive mesenteric
      infarction.
AB  - The AA reports a case of a 64-year-old female patient affected for 3 years by
      systemic lupus erythematosus who developed a massive perforating mesenteric
      infarction. An immediate surgical treatment with resection of the small bowel and
      right colon followed by a side-to-side primary anastomosis between the remaining
      jejunum and transverse colon were performed. The patient died 15 days after
      surgery due to recurrence of a mesenteric and pulmonary thromboembolia.

PMID- 10919028
TI  - Initial experience with the harmonic scalpel in liver surgery.
AB  - BACKGROUND/AIMS: Hepatectomies are generally performed using a crushing clamp or
      by finger fracture. New instruments such as ultrasonic aspirators or water jet
      dissectors are increasingly used for precise dissection of intrahepatic
      structures. An ultrasonically activated scalpel has been introduced, mainly for
      laparoscopic procedures. The potential of this instrument in liver surgery
      remains to be defined. METHODOLOGY: In a prospective study, we have tested the
      harmonic scalpel (Ultracision, Ethicon Endo-surgery) in 16 consecutive patients
      undergoing liver surgery. The ease of parenchymal dissection and the hemostatic
      effect of the ultrasonically vibrating blade was assessed in each operation.
      Blood loss and transfusions were recorded. RESULTS: One patient underwent
      excision of a liver cyst and 15 patients 16 hepatectomies for colorectal
      metastases (7 cases), hepatocarcinoma (5 cases) and other benign or malignant
      conditions (4 cases). The liver was cirrhotic in 4 cases. The performance of the
      harmonic scalpel for dissection, cutting and hemostasis was good or excellent in
      16 operations, and poor in 1 hepatectomy in a cirrhotic liver. Median blood loss
      was 400 mL (range: 0-1200 mL) and 4 patients received blood transfusions.
      CONCLUSIONS: The harmonic scalpel allows efficient section of liver parenchyma,
      precise dissection of intrahepatic structures, good hemostasis and section of
      small intrahepatic vessels.

PMID- 10919029
TI  - Effects of single dose of 50mg captopril in patients with liver cirrhosis and
      ascites.
AB  - BACKGROUND/AIMS: In patients with liver cirrhosis and ascites, the renin
      angiotensin system is usually activated. Such a correlation supports the
      hypothesis that activation of the renin-angiotensin system plays an influential
      role in the pathogenesis of ascites in liver cirrhosis. METHODOLOGY: In this
      study, 25 patients with liver cirrhosis and ascites (10 females, 15 males; age:
      45-67 years) were enrolled. We evaluated the acute effects of converting enzyme
      inhibitor (a single dose of 50 mg captopril taken orally) on glomerular
      filtration rate, effective renal plasma flow, filtration fraction, plasma renin
      activity, and plasma aldosterone. RESULTS: Oral intake of a single 50 mg dose of
      captopril significantly decreased glomerular filtration rate (65 +/- 6
      mL/min/1.73 m2 vs. 53 +/- 9 mL/min/1.73 m2), filtration fraction (21.2 +/- 2.7%
      vs. 15.5 +/- 4.1%), and plasma aldosterone (340 +/- 80 pg/mL vs. 247 +/- 42
      pg/mL), but increased plasma renin activity (2.65 +/- 2.19 ng/mL/hr vs. 11.58 +/-
      2.70 ng/mL/hr) and effective renal plasma flow (312 +/- 41 mL/min/1.73 vs. 356 +/
      60 mL/min/1.73 m2). CONCLUSIONS: We suggest that oral intake of a single dose of
      50 mg captopril can block the renin-angiotension system, and result in changes in
      renal hemodynamics and function in cirrhotic patients with ascites.

PMID- 10919030
TI  - Intravenous nutrition with high-dose fat emulsion and amino acids without glucose
      provision after hepatic resection.
AB  - BACKGROUND/AIMS: Controversy remains regarding the optimal nutrition after
      hepatic resection. We studied the feasibility and efficacy of an intravenous
      nutrition with high-dose fat emulsion and amino acids without glucose provision
      by comparing a glucose-based intravenous nutrition. METHODOLOGY: Twenty-eight
      patients received either glucose-intravenous nutrition (glucose-IVN group:
      glucose, 4.2 g; amino acids, 0.8 g/Kg/day) or high-dose fat emulsion and amino
      acids without glucose provision (HFHA-IVN group: lipids, 2.2 g; amino acids, 1.6
      g/Kg/day) for 7 days after hepatic resection (14 patients in each group).
      Postoperative changes in biochemical tests and plasma levels and arterial-venous
      concentration differences of amino acids and total ketone bodies across the leg
      were compared between the two. RESULTS: The 2 groups were comparable regarding
      perioperative patients' characteristics. None of the patients from either group
      developed any complications. Postoperative glucose levels showed normal in the
      HFHA-IVN group, but elevated in the glucose-IVN group. Seven of the glucose-IVN
      group patients required exogenous insulin administration. Lipid levels were
      decreased in the glucose-IVN group, but remained normal in the HFHA-IVN group.
      The HFHA-IVN group showed higher amino acid levels, higher amino acid release,
      and hyperketonemia and vigorous uptake of ketones by skeletal muscle.
      CONCLUSIONS: These results indicate that dextrose provision is not essential and
      the HFHA-IVN provides an alternative to glucose-based intravenous nutrition in
      patients developing glucose intolerance after hepatic resection.

PMID- 10919031
TI  - Isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques: from
      laboratory to the clinic towards a percutaneous procedure.
AB  - BACKGROUND/AIMS: The success of and our extensive experience with TNF alpha-based
      isolated limb perfusions in patients with unresectable extremity soft tissue
      sarcomas made us explore the possibilities for a similar approach for the
      treatment of hepatic metastases. After experience with the classic surgical
      isolated hepatic perfusion in pigs and in patients, we concluded that the classic
      surgical approach was associated with serious drawbacks i.e., magnitude of the
      procedure with morbidity, lack of repeatability of the procedure, complexity and
      costs. These problems were addressed in a program aimed at developing a
      repeatable method of isolated perfusion of the liver with minimally invasive
      techniques. METHODOLOGY: We validated the methodology of isolated hypoxic hepatic
      perfusion using balloon catheter techniques in pigs. RESULTS: The excellent
      pharmacokinetic profile of the procedure, resulting in very high regional drug
      concentrations and negligible systemic drug concentrations, allowed us to move on
      to the clinic and start to study and further develop this method in a phase I-II
      study using the drug melphalan, in patients with irresectable hepatic metastases.
      CONCLUSIONS: We aim to develop step by step a fully percutaneous approach for
      isolated hypoxic hepatic perfusion.

PMID- 10919032
TI  - HCV infection in the general population of a Greek island: prevalence and risk
      factors.
AB  - BACKGROUND/AIMS: Although HCV seroprevalence in blood donors in Greece is low
      (0.2-0.4%) epidemiologic characteristics of HCV infection in the general
      population have not been studied enough. The objective of this study was to
      examine the seroprevalence of HCV infection and associated risk factors in the
      general population of Zakinthos, a Greek island with a well-defined mixed (urban
      and rural) population. METHODOLOGY: A household health survey was carried out in
      a randomly selected sample of 718 adults. A questionnaire was completed and a
      blood sample was obtained from all participants. Serum samples were tested for
      anti-HCV antibodies by third generation enzyme-linked immunosorbent assay and
      supplemental test. The influence of sociodemographic characteristics and possible
      associated risk factors on the HCV seroprevalence was investigated by logistic
      regression analysis. RESULTS: The overall anti-HCV prevalence was 1.25%. A well
      defined rural area with a significant higher prevalence (6.8% vs. 0.62%; P <
      0.001) was identified. There was a trend of increasing prevalence with age, with
      a significant difference (P < 0.027) between the age groups 15-44 (0%) and over
      45 (2.15%). The logistic regression analysis confirmed a significant association
      between anti- HCV positivity and: increasing age (P < 0.001), history of blood
      transfusion (0.0001), intramuscular injections (P < 0.04). CONCLUSIONS: The
      results of this field-survey in a well-defined general population, indicates that
      HCV seroprevalence (1.25%) is much higher than that of blood donors in the same
      area. The increasing prevalence with age and the association with parenteral
      exposure indicates that HCV infection can mainly be attributed to parenteral
      techniques in the past. The identification of a concrete rural area with
      particularly high seroprevalence needs further study of the whole population of
      the area.

PMID- 10919033
TI  - N-acetylcysteine in acute hepatic failure (non-paracetamol-induced).
AB  - BACKGROUND/AIMS: Acute liver failure is a serious condition associated with poor
      prognosis. It may be associated with changes in systemic hemodynamics, i.e.,
      tissue hypoxia, which contributes to multiple-organ failure. Recent studies have
      shown that N-acetylcysteine administered to patients with fulminant hepatic
      failure (paracetamol-induced) increases oxygen delivery and improves survival.
      The aim of this pilot study was to evaluate N-acetylcysteine administration to
      patients with non-paracetamol-induced acute liver failure and assess its effect
      on the clinical course and outcome. METHODOLOGY: N-acetylcysteine was
      administered at presentation to 7 patients with non-paracetamol-induced acute
      liver failure. Patients were followed for changes in clinical parameters (grade
      of encephalopathy), coagulation factors, biochemical parameters and outcome.
      RESULTS: Clinically, 3 patients who initially had grade O/II encephalopathy, did
      not progress, and have fully recovered. The mean peak prothrombin time, serum
      factor V, aspartate aminotransferase and alanine aminotransferase levels, all
      significantly improved. Four patients (57%) have recovered fully (1 patient,
      although fully recovered, died later from an unrelated cause). Two patients
      required orthotopic liver transplantation and 1 patient died. N-acetylcysteine
      administration may have prevented progression to grade III/IV encephalopathy and
      improved serum coagulation factors. This may account for its beneficial effect on
      survival in patients who had poor prognostic criteria at base-line. No side
      effects of the drug were noted. CONCLUSIONS: This study suggests that N
      acetylcysteine administration should be considered in all patients with acute
      liver failure.

PMID- 10919034
TI  - Experimental studies of new embolizing material for portal vein embolization.
AB  - BACKGROUND/AIMS: Preoperative portal vein embolization induces hypertrophy of the
      future remnant liver and atrophy of the liver to be resected. This procedure has
      been used recently to avoid hepatic failure in extensive hepatic resection, but
      an adequate embolizing material has not been developed. This experimental study
      investigated the embolization effect of a newly devised embolizing material in
      dogs. METHODOLOGY: The left branch of the portal vein was embolized with an
      emulsion of polidocanol and gelatin sponge. We studied the changes in liver
      weight and biochemical data up to 8 weeks after embolization. Pathological
      examination of the embolized portal vein and radiological study of the embolizing
      effect were performed. RESULTS: Complete obstruction of the portal vein was
      maintained until 8 weeks after embolization. Sufficient hypertrophy of the non
      embolized liver and atrophy of the embolized liver were obtained during this
      examination. No serious complication was observed. CONCLUSIONS: The mixture of
      polidocanol and gelatin sponge seems to ensure perfect portal embolization
      without recanalization. This embolizing material is suitable for portal
      embolization.

PMID- 10919035
TI  - Effects of angiotensin-converting enzyme inhibitors and sclerotherapy on portal
      hemodynamics in patients with portal hypertension.
AB  - BACKGROUND/AIMS: Since pharmacotherapy of portal hypertension has always been a
      subject of wide interest, we decided to study the effects of different
      angiotensin-converting enzyme inhibitors and endoscopic sclerotherapy on portal
      hemodynamics in patients with portal hypertension and bleeding esophageal
      varices. METHODOLOGY: The study included 72 patients with portal hypertension
      divided into 6 equal groups. Endoscopic sclerotherapy was done to all patients
      every 2 weeks for 3 months. In addition, the first 5 groups of patients were
      maintained on angiotensin-converting enzyme inhibitors for 3 months as follows:
      group I on perindopril, II on ramipril, III on fosinopril, IV on lisinopril and V
      on captopril. Portal hemodynamics were determined before and after therapy (using
      an ultrasonic duplex system). New Doppler portal indices were derived and portal
      vein kinetic pressure was estimated for the first time by using data derived from
      the ultrasonic duplex system. RESULTS: 1) Short-term endoscopic sclerotherapy
      alone resulted in significant elevation of portal vein kinetic pressure, wall
      stress index and flow volume (P < 0.01) and non-significant increase in the total
      portal circulation resistance index (P > 0.05) and significantly decreased portal
      vein compliance and distensibility indices (P < 0.05); 2) Angiotensin-converting
      enzyme inhibitors reduced the maximum and average portal velocities, the portal
      flow volume, total portal circulation resistance index and increased portal vein
      compliance and distensibility indices, hence they reduced the portal vein kinetic
      pressure significantly in group IV (P < 0.05 for the flow volume and P < 0.01 for
      other indices); 3) The only side effect encountered was allergic cough (in 8.33%
      of patients). No effects were noticed on the pulse, systolic, diastolic or mean
      blood pressures or Child-Pugh Score of liver disease. CONCLUSIONS: 1) Angiotensin
      converting enzyme inhibitors when added to endoscopic sclerotherapy can
      ameliorate the effects of the latter on portal hemodynamics in patients with
      portal hypertension; 2) Portal vein kinetic pressure, total portal circulation
      resistance index, portal vein wall stress index, compliance and distensibility
      indices are new Doppler portal indices that proved to be of value in the follow
      up of patients with portal hypertension under sclerotherapy alone or in
      conjunction with pharmacotherapy; 3) Angiotensin-converting enzyme inhibitors are
      safe drugs that can be used for portal decompression with endoscopic
      sclerotherapy. Their use as sole portal anti-hypertensive agents still awaits
      further studies.

PMID- 10919036
TI  - Prostaglandin E1 reduces thromboxane A2 in hepatic ischemia-reperfusion.
AB  - BACKGROUND/AIMS: Prostaglandin E1 is well documented to exert cytoprotective
      effects in ischemia-reperfusion injury in the liver. This study was designed to
      evaluate the changes in prostanoid concentrations and to delineate the mechanism
      of the cytoprotective effect of prostaglandin E1 in hepatic ischemia-reperfusion
      injury. METHODOLOGY: Mongrel dogs were divided into 3 groups: a control group, an
      ischemia-reperfusion group (I-R group), and a group that received prostaglandin
      E1 and was then subjected to ischemia-reperfusion. Liver ischemia was produced
      for 60 min using the Pringle maneuver. The concentrations of aspartate
      aminotransferase, alanine aminotransferase, prostaglandin I2, thromboxane A2, and
      lipid peroxides in hepatic venous blood were examined before and after the
      Pringle maneuver in the latter 2 groups, and at the corresponding points in the
      control group. RESULTS: In the I-R group, aspartate aminotransferase and alanine
      aminotransferase after ischemia-reperfusion were significantly higher than those
      in the control group, and these values also rose significantly after ischemia
      reperfusion in the prostaglandin E1-treated group. However, prostaglandin E1
      administration suppressed significantly the increase compared with the I-R group.
      In the I-R group, prostaglandin I2, thromboxane A2, and lipid peroxide production
      in the liver increased 5 min after unclamping. The increases in thromboxane A2
      and lipid peroxide production before and after ischemia-reperfusion were
      decreased, and prostaglandin I2 production was increased before ischemia
      reperfusion in the group that was pretreated with prostaglandin E1. CONCLUSIONS:
      Prostaglandin E1 is involved protecting against warm ischemic liver damage by not
      only suppressing the increased thromboxane A2 production, but also by increasing
      prostaglandin I2 production.

PMID- 10919037
TI  - Tissue inhibitors of metalloproteinases in liver and serum/plasma in chronic
      active hepatitis C and HCV-induced cirrhosis.
AB  - BACKGROUND/AIMS: The development of liver cirrhosis can be described as a process
      of tissue remodeling, which involves increased matrix turnover. In order to
      determine whether the expression of tissue inhibitors of metalloproteinases
      (TIMPs) reflects these changes and can be used as a marker for the activity of
      ongoing fibrosis, we studied TIMP-1, 2 and -3 in liver and serum/plasma of
      patients with chronic hepatitis C, hepatitis C virus-induced cirrhosis and
      healthy controls. METHODOLOGY: Northern and Western blot analysis, reverse
      transcriptase polymerase chain reaction and ELISA measurements were performed.
      RESULTS: Reverse transcriptase polymerase chain reaction showed transcripts of
      all 3 TIMPs in liver tissue. TIMP-1 and -2 were also detectable in lymphocytes
      and granulocytes, which did not contain any TIMP-3. mRNA for TIMP-1 and -3, but
      not for TIMP-2, was detectable by Northern blot in normal human liver and
      increased in fibrosis and cirrhosis. Western blotting demonstrated the presence
      of all 3 TIMP proteins in healthy liver. TIMP-1 and TIMP-2 levels increased, but
      TIMP-3 was unchanged in cirrhosis compared to normal tissue. ELISA studies showed
      that the increase of TIMP-1 occurred only in advanced cirrhosis, while levels did
      not elevate in chronic hepatitis with or without fibrosis. In plasma, some of the
      cirrhotic patients had very high TIMP-1 values, while mean circulating TIMP-1
      levels were not significantly different between controls, hepatitis C and
      cirrhotic patients. Serum TIMP-2 levels were higher in chronic hepatitis and
      cirrhosis than in controls, but did not differ between patients with or without
      histologic fibrosis. CONCLUSIONS: In normal human liver there is expression of
      all 3 TIMPs studied. The amount of hepatic TIMP-1 protein increases late in the
      fibrotic process, and there is a weak correlation between the activity of
      fibroproliferation and hepatic or circulating amounts of TIMP-1. Currently there
      is no evidence that measurement of TIMP-2 and TIMP-3 in liver or blood improves
      diagnosis of fibroproliferation in chronic hepatitis C.

PMID- 10919038
TI  - Ornithine decarboxylase activity in the non-cancerous hepatic tissue of patients
      with hepatocellular carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma may develop in patients with chronic
      hepatitis and cirrhosis. Active hepatitis is an important etiologic factor in the
      development of hepatocellular carcinoma. We measured ornithine decarboxylase
      activity, an important enzyme during cell proliferation, in non-cancerous hepatic
      tissue in patients with hepatocellular carcinoma. METHODOLOGY: Thirty-four
      patients who underwent liver resection for hepatocellular carcinoma were the
      subjects of this study. Hepatitis B surface antigen was detected in 7 patients
      (HBV group) and hepatitis C virus antibody was detected in 27 patients (HCV
      group). Tissue ornithine decarboxylase activity was measured. Histologic severity
      in active hepatitis (activity score) and degree of fibrosis (staging score) were
      determined. RESULTS: Ornithine decarboxylase activity was significantly higher in
      the HCV group than in the HBV and control groups. In all patients, ornithine
      decarboxylase activity correlated directly with the histologic activity score and
      the histologic staging score. In the HCV group, ornithine decarboxylase activity
      correlated with the histologic activity score. CONCLUSIONS: Ornithine
      decarboxylase activity in non-cancerous hepatic tissue correlated with the
      severity of active hepatitis and degree of fibrosis. In patients with hepatitis C
      virus, active hepatitis with increased ornithine decarboxylase activity is an
      important factor in the development of hepatocellular carcinoma.

PMID- 10919039
TI  - Percutaneous ethanol injection for hepatocellular carcinoma originating in the
      caudate lobe.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma originating in the caudate lobe is rare
      and the treatments for caudate hepatocellular carcinoma were thought difficult,
      because of its unique location at hepatic resection, or because of complex
      arterial supply at transcatheter arterial embolization. Percutaneous ethanol
      injection is an effective treatment for small hepatocellular carcinoma. The aim
      of this study was to assess the efficacy of percutaneous ethanol injection for
      hepatocellular carcinoma originating in the caudate lobe. METHODOLOGY: During the
      past 4 years, 7 patients with 7 hepatocellular carcinomas originating in the
      caudate lobe underwent percutaneous ethanol injection as a curative treatment.
      The outcomes of percutaneous ethanol injection and the survival of the 7 patients
      were evaluated. RESULTS: Percutaneous ethanol injection was successfully carried
      out with no severe complications in all patients. During follow-up periods local
      recurrence was noticed in a patient, that was treated with percutaneous ethanol
      injection again. Four patients had recurrence in other parts of the liver, who
      were treated with percutaneous ethanol injection alone or percutaneous ethanol
      injection and transcatheter arterial embolization. Six patients were alive for 12
      55 months after percutaneous ethanol injection and 1 patient died of hepatic
      failure 15 months after the procedure. CONCLUSIONS: Percutaneous ethanol
      injection was a safe and effective treatment, and it would be an alternative
      therapy for hepatocellular carcinoma originating in the caudate lobe.

PMID- 10919040
TI  - Soluble interleukin-2 receptor and interleukin-10 levels in patients with chronic
      hepatitis B infection.
AB  - BACKGROUND/AIMS: In the current investigation, we evaluated patients with
      hepatitis B infection to determine whether serum soluble interleukin-2 receptor
      and interleukin-10 levels were changed and whether the degree of these changes in
      serum levels correlated with histologic severity of hepatitis related liver
      injury. METHODOLOGY: 25 patients diagnosed of chronic active B hepatitis, 25
      asymptomatic hepatitis B carriers, 25 healthy people with antibody to hepatitis B
      surface antigen and 20 healthy people without any hepatitis marker positivity
      were included in the study. Serum interleukin-10 and soluble interleukin-2
      receptor levels were measured. The association between liver pathology, HBV DNA,
      serum transaminase values and these parameters were researched. RESULTS: Serum
      soluble interleukin-2 receptor and interleukin-10 levels were significantly
      higher in chronic hepatitis cases and asymptomatic carriers than that of others
      (P < 0.01). Serum interleukin-10 levels correlated with histological activity
      index and HBV DNA values (r = 0.7, P < 0.01) but not with soluble interleukin-2
      receptor levels and transaminase values. CONCLUSIONS: Our results support the
      observation that interleukin-10 and soluble interleukin-2 receptor may play an
      important role in the inappropriate regulation of immune response in patients
      with chronic hepatitis B virus infection and interleukin-10 may be responsible
      for chronicity.

PMID- 10919041
TI  - Surgery for mixed hepatocellular and cholangiocellular carcinoma.
AB  - BACKGROUND/AIMS: Mixed tumors composed of hepatocellular carcinoma and
      cholangiocellular carcinoma are rare. In this report, the clinicopathologic
      characteristics and treatment outcome of four patients with mixed hepatocellular
      and cholangiocellular carcinomas are described. METHODOLOGY: Of 539 patients with
      primary liver cancer who underwent hepatic resection in our department over a 17
      year period, 4 were diagnosed with mixed hepatocellular and cholangiocellular
      carcinoma. The clinicopathological features and treatment outcomes of these 4
      patients were investigated. RESULTS: All 4 patients were positive for hepatitis C
      virus antibody and had hypervascular tumors. Tumor resection was performed for
      all patients. Three underwent lymph node dissection. At the time of this study, 1
      patient was alive without recurrence 12 months after surgery. The other patients
      died within 28 months of surgery. CONCLUSIONS: Mixed tumors should be considered
      in patients with a liver mass and increased serum carcinoembryonic antigen and
      carbohydrate antigen 19-9 concentrations, a low alpha-fetoprotein concentration,
      and hypervascularity. The cholangiocellular carcinoma component appears to
      determine the prognosis.

PMID- 10919042
TI  - Hepatectomy for hepatocellular carcinoma in a renal transplant patient--report of
      a case and literature review.
AB  - A 45-year-old woman underwent hepatectomy for hepatocellular carcinoma developing
      after 2 renal transplants. She had a solitary hepatocellular carcinoma and
      central bisegmentectomy of the liver was performed. Administration of
      immunosuppressants was continued to maintain renal function in the perioperative
      period. Although our patient suffered from severe pneumonia postoperatively, she
      recovered without a decline in renal function. She has been alive for 1 year and
      3 months after hepatectomy with hepatocellular carcinoma recurrence in the
      remnant liver. Any patient undergoing hepatectomy for hepatocellular carcinoma
      after renal transplantation should be managed as an immunocompromised host.
      Previously reported cases of hepatectomy for hepatocellular carcinoma in renal
      transplant recipients were reviewed.

PMID- 10919043
TI  - Successful emergency treatment with a transjugular intrahepatic portosystemic
      shunt for life-threatening Budd-Chiari syndrome with portal thrombotic
      obstruction.
AB  - We report successful treatment of acute severe Budd-Chiari syndrome with portal
      venous thrombosis. The prognosis of patients with this condition is poor, because
      the therapeutic options are limited. A 38-year-old woman with polycythemia vera
      was admitted in a critical condition, and Budd-Chiari syndrome complicated by
      portal venous thrombosis was diagnosed. Tissue plasminogen activator and
      urokinase were infused systemically and were partially effective. Transjugular
      intrahepatic portosystemic shunting to reduce the high portal venous pressure was
      performed successfully and, eventually, her general condition improved. Our
      experience indicates that emergency transjugular intrahepatic portosystemic
      shunting is an effective therapeutic modality for controlling portal hypertension
      in patients with severe Budd-Chiari syndrome with portal venous thrombosis.

PMID- 10919045
TI  - Efficacy of hepatic arterial infusion of prostaglandin E1 in the treatment of
      postoperative acute liver failure--report of a case.
AB  - Prostaglandin E1 (PGE1) has received attention for its protective effects against
      various types of liver damage. However, it is known that approximately 70% of
      PGE1 is inactivated during a single passage through the lung. Therefore, direct
      infusion of PGE1 into the liver bloodstream is preferable to intravenous
      infusion. A 66-year-old man with hepatocellular carcinoma with liver cirrhosis
      developed postoperative acute liver failure following posterior segmentectomy
      under hepatic total vascular exclusion exceeding 1 hour. Because his liver
      function did not recover in spite of plasma exchange starting on postoperative
      day 8 and intravenous infusion of PGE1, hepatic arterial continuous infusion of
      PGE1 at a rate of 0.01 microgram/kg/min was carried out for 7 days from
      postoperative day 17. Immediately after the start of the arterial infusion, the
      bile flow significantly increased compared to before the arterial infusion, and
      the serum total bilirubin level decreased thereafter and finally recovered from
      the hepatic failure. In addition to its highly efficient drug delivery, the
      hepatic arterial infusion of PGE1 seems to be more advantageous in oxygen
      delivery to the liver compared with intravenous infusion. In conclusion, the
      hepatic arterial infusion of PGE1 may be useful in the treatment of acute liver
      failure.

PMID- 10919044
TI  - Hepatocellular carcinoma followed by Waldenstrom's macroglobulinemia: a case
      report.
AB  - A case of hepatocellular carcinoma associated with Waldenstrom's
      macroglobulinemia is reported. During treatment and follow-up of hepatocellular
      carcinoma, a 54-year-old man was found to have a progressive monoclonal increase
      in serum IgM level and subsequently was diagnosed as having Waldenstrom's
      macroglobulinemia. Chemotherapy was carried out to prevent hyperviscosity
      syndrome due to Waldenstrom's macroglobulinemia without any surgical management
      for hepatocellular carcinoma. The association of these diseases is quite rare;
      only 6 cases have been reported in the literature, and this is the first case in
      which hepatocellular carcinoma preceded Waldenstrom's macroglobulinemia.

PMID- 10919046
TI  - A resected case of combined hepatocellular carcinoma and cholangiocarcinoma
      associated with cystic formation.
AB  - Combined hepatocellular carcinoma and cholangiocarcinoma is a rare tumor. In
      addition, both hepatocellular carcinoma and cholangiocarcinoma are rarely
      associated with cystic lesions. We herein present a 62-year-old Japanese woman
      with combined hepatocellular carcinoma and cholangiocarcinoma which was
      associated with a rapidly enlarging cystic lesion. Both abdominal ultrasonography
      and computed tomography revealed a cyst with a solid portion in the left hepatic
      lobe. A partial hepatectomy was performed on the basis of a tentative diagnosis
      of a cystadenocarcinoma of the liver, while the diagnosis based on
      immunohistochemical studies was combined hepatocellular carcinoma and
      cholangiocarcinoma with cystic formation. The patient died of tumor recurrence,
      such as intrahepatic metastases and extensive lymph node metastases, 6 months
      after the operation. The prognosis of this entity, which has never been reported
      in the English medical literature and is difficult to preoperatively
      differentiate from hepatic cystadenocarcinoma, therefore seems to be extremely
      poor.

PMID- 10919047
TI  - New epidemiological data on liver oncogenesis.
AB  - The purpose of this review is to address and discuss the following: a) the
      malignant transformation of hepatocytes may occur, irrespective of the etiologic
      agent, in the context of increased cellular turnover induced by chronic hepatic
      damage and regeneration, with genetic mutations being a frequent event prior to
      the development of this tumor; b) although it is clear that hepatitis B virus
      induced chronic liver injury, regeneration and cirrhosis is a major risk factor
      for hepatocellular carcinoma development, there are also several reports of the
      direct carcinogenic effects of hepatitis B virus. For instance, integration of
      hepatitis B virus DNA can directly induce chromosomal rearrangements and viral
      gene product transactivating properties may influence cellular genes important in
      the control of the growth process; c) hepatitis C virus and other risk agents,
      including alcohol, environmental factors and metabolic diseases may operate,
      mainly through chronic liver damage that progress to liver cirrhosis, a major
      predisposing factor for the development of hepatocellular carcinoma, regardless
      of etiology; d) at the molecular level, the interaction between oncogenes, tumor
      suppressor genes (with or without aflatoxins and hepatitis B virus) and several
      growth factors may play an additional role in hepatocellular carcinoma
      development.

PMID- 10919048
TI  - A phase II study of sequential methotrexate and 5-fluorouracil in metastatic
      pancreatic cancer.
AB  - BACKGROUND/AIMS: Sequential administration with methotrexate and 5-fluorouracil
      (sequential MTX/5-FU) has synergistic cytotoxic activity for several malignant
      diseases, but its activity in pancreatic cancer has not been fully evaluated. The
      aim of this study was to evaluate the antitumor activity and toxicity of
      sequential MTX/5-FU in metastatic pancreatic cancer. METHODOLOGY: All patients
      were required to have a pathologic diagnosis of pancreatic adenocarcinoma with
      measurable metastatic lesions, and no prior chemotherapy. Sequential MTX/5-FU was
      administered weekly as followed; MTX 100 mg/m2 intravenous bolus infusion was
      given, followed 3 h later by 5-fluorouracil 600 mg/m2 intravenous infusion over
      30 min. RESULTS: Thirty-one patients were enrolled and assessable for response
      and toxicity. There were no complete responses, 4 partial responses, 10 no change
      and 17 progressive disease. The response rate was 12.9% (95% confidence interval:
      1.1-24.7%) and the duration of response was 7.1 months (range: 5.5-9.1 months).
      The median survival was 4.0 months. Chemotherapy was well tolerated, although
      grade 3-4 toxicities such as neutropenia and diarrhea were seen infrequently.
      CONCLUSIONS: The sequential MTX/5-FU had marginal antitumor activity with mild
      toxicity against metastatic pancreatic cancer.

PMID- 10919049
TI  - In vivo evaluation of long-term patency of pancreaticoenterostomy after Whipple
      operation.
AB  - BACKGROUND/AIMS: The aim of this study was to examine the long-term patency of
      pancreaticoenterostomy in vivo. METHODOLOGY: Evaluation of the patency of the
      pancreaticoenterostomy was conducted in 12 patients who had undergone the Whipple
      procedure. After intravenous infusion of secretin (1 microgram/kg), the diameter
      of the pancreatic duct was taken at 1, 3, 5, 15, 20 and 25 min by means of
      ultrasonography. We estimated the degree of anastomotic stricture by the maximal
      dilatation ratio [MDR: Maximal value (Dmax)/basal value (D0)]. The patients
      underwent pancreatic exocrine function tests before and 1-2 years after surgery.
      RESULTS: Maximal ductal dilatation was noted from 3 min of 15 min after secretin
      infusion, thereafter ductal diameter gradually diminished and returned to its
      basal value at 25 min. Maximal dilatation ratio ranged from 1.3-2.5, 1.7 +/-
      0.12. There was a good negative relationship between the maximal dilatation ratio
      and pancreatic exocrine function. Based on the result of chi 2 analysis, we
      judged anastomotic stricture to be present in 2 patients with maximal dilatation
      ratio above 2.0. In these 2 patients, preoperative pancreatic exocrine function
      recoveries were 69 and 48%, while postoperative pancreatic exocrine function
      recoveries were 13.8 and 18%, respectively. In the other 10 patients, there was
      no difference between preoperative and postoperative value of pancreatic exocrine
      function. CONCLUSIONS: The present method permits safe and non-invasive
      evaluation of the patency of pancreaticoenterostomy.

PMID- 10919050
TI  - Plasma cholecystokinin and somatostatin levels in chronic pancreatitis patients.
AB  - BACKGROUND/AIMS: The existence of a negative-feedback mechanism between
      pancreatic enzyme secretion and intraduodenal proteases and the role of
      cholecystokinin in its mediation in humans is debatable. The presence of such a
      feedback mechanism in chronic pancreatitis patients with exocrine enzyme
      deficiency possibly leads to an increase in cholecystokinin plasma levels.
      Somatostatin has been used in many studies in the therapy of pain in chronic
      pancreatitis and plays a role in the regulation of cholecystokinin levels,
      however data on its plasma levels are still lacking. METHODOLOGY: Basal and the
      postprandial cholecystokinin and somatostatin levels in 30 patients with chronic
      pancreatitis (11 with severe chronic pancreatitis and 19 with mild chronic
      pancreatitis) were measured 14 days after discontinuation of enzymatic
      substitution therapy and then were compared with the levels taken from 25 healthy
      subjects. RESULTS: The cholecystokinin postprandial plasma levels were
      significantly higher in patients with chronic pancreatitis when compared with
      those of healthy individuals (P < 0.01). Basal, somatostatin, cholecystokinin and
      postprandial somatostatin levels were not significantly higher than those in
      healthy subjects. There was no correlation between basal and postprandial levels
      of cholecystokinin and somatostatin in our study. CONCLUSIONS: The
      cholecystokinin postprandial plasma levels were significantly higher in all
      patients with chronic pancreatitis when compared with healthy individuals, which
      suggests the role of cholecystokinin in the feedback control of pancreatic
      secretion.

PMID- 10919051
TI  - Evaluation of PCNA, p53, K-ras and LOH in endocrine pancreas tumors.
AB  - BACKGROUND/AIMS: The object of this study was to evaluate the characters of the
      endocrine pancreas tumors including proliferative activity, p53 mutation, K-ras
      mutation and microsatellite instability. METHODOLOGY: The 13 endocrine tumors of
      the pancreas were enrolled in this study. There were 8 hypervascular tumors and 4
      normo- or hypovascular tumors. All cases were immunohistochemically characterized
      in paraffin sections for the presence of proliferating cell nuclear antigen and
      p53 protein. Mutation in K-ras at codon 12 was detected by the Mutant-allele
      specific amplification system. Microsatellite instability was examined by using
      frozen tissues in the 2 cases. RESULTS: Proliferating cell nuclear antigen
      labeling index range was 0.00-0.62 (0.26 +/- 0.23). p53 was positive in 4/13
      tumors. K-ras codon 12 mutation was not detected in any tumors. PCNA LI was
      significantly lower in hypervascular tumors (0.16 +/- 0.20) than normo- or
      hypovascular tumors (0.44 +/- 0.17) (P < 0.05). PCNA LI was significantly lower
      in the p53-positive tumors (0.48 +/- 0.17) than the p53-negative tumors (0.17 +/-
      0.18) (P < 0.05). K-ras codon 12 mutation was not detected in any tumors. Loss of
      heterozygosity in 3p was detected in 1 tumor. CONCLUSIONS: Hypervascular
      endocrine pancreas tumors have low proliferative activity. p53 mutation
      influences proliferation as the late event of tumor progression.

PMID- 10919052
TI  - Patterns of lymph node metastasis in carcinoma of the ampulla of Vater.
AB  - BACKGROUND/AIMS: Identification of lymph node metastasis may guide surgical
      therapy. The aim of this study was to clarify the lymphatic spread in ampullary
      carcinoma in relation to local tumor extent (pT category in the pTNM
      classification). METHODOLOGY: The distribution and number of lymph node
      metastases were histologically examined in 35 patients with ampullary carcinoma.
      RESULTS: Lymph node metastases were present in 10 of 15 patients (67%) with pT2
      tumor and in 10 of 11 (91%) with pT3 tumor. Nodal involvement was not identified
      in 9 patients with pT1 tumor. The incidence of node-positive patients was higher
      in pT2 and pT3 tumors than in pT1 tumors (P < 0.01). The total number of positive
      nodes per node-positive patient was greater in pT3 tumors than in pT2 tumors
      (mean 3.50 vs. 1.30, P < 0.001). All node-positive patients had metastasis to the
      posterior pancreaticoduodenal node. The number of positive nodes per node
      positive patient in both the posterior pancreaticoduodenal and the superior
      mesenteric region was greater in pT3 tumors than in pT2 tumors (P < 0.01 and P <
      0.05). CONCLUSIONS: With increasing pT category in ampullary carcinoma, lymphatic
      spread extended from the posterior pancreaticoduodenal region to the superior
      mesenteric nodes.

PMID- 10919053
TI  - Preoperative localization of pancreatic insulinoma by selective intraarterial
      calcium injection and hepatic venous sampling.
AB  - Preoperative localization of insulinomas is desirable by most surgeons. Imaging
      with ultrasonography, computed tomography, magnetic resonance imaging, nuclear
      medicine and angiography may fail to demonstrate these small tumors in up to 10%,
      while a smaller percentage may be missed even after careful surgical exploration
      and intraoperative ultrasonography. Selective intraarterial injection of calcium
      with hepatic venous sampling has been reported to be a very accurate technique
      for preoperative localization of insulinomas. We report such a case where the
      clinical symptoms were highly suggestive but imaging algorithm failed to reveal
      any lesion and we review the literature.

PMID- 10919054
TI  - Successful surgical resection of solid cystic tumor of the pancreas with multiple
      liver metastases and a tumor thrombus in the portal vein.
AB  - We report a case of solid cystic tumor of the pancreas with widespread liver
      metastases and a tumor thrombus in the portal vein. The patient was a 43-year-old
      woman. She was referred because of an upper abdominal mass and weight loss.
      Computed tomography disclosed a 10-cm cystic and calcified mass in the body and
      tail of the pancreas and multiple masses in the liver. She underwent a distal
      pancreatectomy with splenectomy, extended right lobectomy, and partial resection
      of the liver. All the tumors were completely resected despite the presence of 20
      liver metastases. Histopathological studies showed a tumor thrombus in the
      intrahepatic portal vein. The patient is well without any signs of recurrence 8
      months after the operation. Aggressive surgical resection is considered to yield
      a good outcome for solid cystic tumor with liver metastases and tumor thrombus of
      the portal vein.

PMID- 10919055
TI  - Surgical outcome of curative resection in patients with Borrmann type IV gastric
      carcinoma with particular reference to the extent of lymph node metastasis.
AB  - BACKGROUND/AIMS: The prognosis after curative resection for Borrmann type IV
      carcinoma, according to the extent of lymph node metastasis, is poorly
      understood. METHODOLOGY: The surgical outcome of curative resection was examined
      in 78 patients with T2-T3 Borrmann type IV gastric carcinomas, with particular
      reference to the extent of lymph node metastasis. RESULTS: The 5-year survival
      rate was 35.7% for the n0 patients, 27.8% for the n1 patients, 18.2% for the n2
      patients and 0% for the n3 or n4 patients. The survival curve for the n3 or n4
      patients differed significantly from those of the n0 (P < 0.0001), n1 (P =
      0.0009) and n2 (P = 0.0203) patients. However, no other statistically significant
      differences between the curves were found. CONCLUSIONS: The results of the
      present study indicate that patients with Borrmann type IV carcinoma of the
      stomach may indeed be cured by curative surgery, and that the surgical outcome of
      this disease does not depend on the extent of lymph node metastasis under
      curative resection if lymph node metastasis is restricted to the n2 lymph nodes.

PMID- 10919056
TI  - Paraaortic lymphadenectomy in patients with advanced carcinoma of the upper-third
      of the stomach.
AB  - BACKGROUND/AIMS: According to current TNM classification, paraaortic nodes
      involvement in gastric cancer is now distant metastasis. Anatomically, however,
      proximal gastric cancer may drain preferentially to the left-paraaortic area
      which represents a regional lymph-node basin. METHODOLOGY: Seventy-five patients
      who underwent an extended gastrectomy with paraaortic lymphadenectomy for
      advanced carcinoma of the upper-third of the stomach were retrospectively
      studied. RESULTS: Of the 75 patients, 55 (73.3%) were positive for nodal
      metastasis and 21 (28.0%) had paraaortic nodes involvement. Paraaortic nodes
      involvement tended to be left-sided (the left side of the aorta around the left
      renal vein) and its incidence did not increase as the overall number of
      infiltrated nodes increased. Five (23.8%) of the 21 patients with paraaortic
      nodes involvement did not have nodal metastases in the paraceliac area. Overall
      survival was not different whether or not paraaortic nodes involvement was
      present, but was dependent on the overall number of infiltrated nodes (viz. 10
      vs. > 10). Eight (22.2%) of 36 patients with 1-10 infiltrated nodes had PNI, with
      a 5-year survival rate of 46.9%. CONCLUSIONS: Removal of lymph nodes around the
      left renal vein should be included during extended gastrectomy in patients with
      advanced carcinoma of the upper-third of the stomach. Left-paraaortic
      lymphadenectomy may benefit such patients if the overall number of infiltrated
      nodes is low (viz. 10).

PMID- 10919057
TI  - Video-endoscopic ultrasonography in staging gastric carcinoma.
AB  - BACKGROUND/AIMS: Clinical staging of gastric carcinoma is important in designing
      the strategy of treatment. Early gastric carcinomas can be treated by minimally
      invasive therapy, whereas advanced gastric carcinomas should be treated by
      surgery with or without combined chemotherapy. This study was undertaken to
      evaluate the accuracy and limitations of video type endoscopic ultrasound in
      preoperative staging of gastric cancer and assessing lymph node metastasis.
      METHODOLOGY: Seventy-four patients with gastric carcinoma were preoperatively
      staged using video-endoscopic ultrasonography, performed by the same
      gastroenterologist. RESULTS: Sixty-three out of the 74 (85%) patients were
      correctly staged by endoscopic ultrasonography. The diagnostic accuracy rate was
      100% for T1, 74% for T2, 87% for T3, and 86% for T4. Overstaging occurred in 11%
      due to peritumoral inflammation. Understaging occurred in 4% due to microinvasion
      of carcinomatous tissue or deeper organ invasion. The diagnosis of lymph node
      metastasis was confirmed in 72% of cases. Sensitivity and specificity was 74% and
      86%, respectively. CONCLUSIONS: Endoscopic ultrasonography has a high accuracy
      rate in staging gastric carcinoma but still has its limitations in evaluating
      regional lymph node metastasis, despite using a new generation video-endoscopic
      ultrasonography.

PMID- 10919058
TI  - Computed tomography (CT) findings of gastric rupture after blunt trauma.
AB  - A 49-year-old carpenter was hit by timber around his upper abdomen 1 hour after
      breakfast. Immediate computed tomography was taken, followed by emergency
      laparotomy showing gastric rupture accompanied with hemorrhage from the superior
      mesenteric vein. Hemostasis and distal partial gastrectomy followed by Billroth-I
      anastomosis reconstruction was performed. Here, we report the abdominal computed
      tomography findings from a patient with gastric rupture after blunt trauma. The
      present case, which is only the second such case reported in English literature,
      suggested that computed tomography is useful for assessing associated injuries in
      gastric rupture patients, for detecting intraperitoneal free air which can be
      missed by X-rays, and for locating the laceration of the rupture.

PMID- 10919059
TI  - Extended lymph-node dissection in gastric cancer: standard, selective or
      unnecessary procedure?
AB  - The effectiveness of extended lymph-node dissection for patients with gastric
      cancer still remains unclear because favorable results reported by Japanese and
      some Western observational studies could not be confirmed by two recent European
      randomized trials. Because the surgeon's experience with extended node dissection
      and the node preservation of spleen and pancreas are predominant factors
      influencing survival, more data from well-designed and conducted randomized
      trials considering these variables are needed to establish whether extensive
      lymphadenectomy improves survival in gastric cancer patients.

PMID- 10919060
TI  - Mucosal immune responses and risk of respiratory illness in elite athletes.
AB  - This review focuses on studies of mucosal 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. 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 hours. Training at an intense level can
      result in a chronic suppression of mucosal immunoglobulin levels. 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. The nature of the respiratory illnesses in some elite athletes is still
      uncertain. Recent data indicate viral reactivation may be a significant cause of
      the respiratory symptoms. Despite suppression of mucosal immune parameters, elite
      athletes are capable of normal responses to novel oral vaccinations, indicating
      that mucosal immune mechanisms are intact.

PMID- 10919061
TI  - Exercise and inflammatory bowel disease: immunological aspects.
AB  - Exercise may promote a healthy life, improving functional capacities. Little is
      known about the effects of physical activity in inflammatory bowel disease.
      Altered immunity is implicated in the pathogenesis of inflammatory bowel
      diseases. An acute, albeit transient acute immune response, follows heavy
      endurance exercise. Epidemiological data support the role of physical activity in
      lowering the risk of inflammatory bowel disease. Moderate physical exercise (60%
      VO2max) does not cause significant changes in symptoms, intestinal transit time,
      and permeability. Neutrophil function appears to be primed at basal conditions
      with significant activation after exercise. At present, mild exercise can be
      recommended to patients with quiescent inflammatory bowel disease as well as
      other chronic diseases such as rheumatoid arthritis, while caution is still
      needed for active disease patients. Patients with inflammatory bowel disease show
      a reduced exercise capacity after surgery, especially after extensive resections.

PMID- 10919062
TI  - Modulation of the immune system by the autonomic nervous system and its
      implication in immunological changes after training.
AB  - This review examines the role of the autonomic nervous system in the regulation
      of the immune system to understand the alteration of immunological parameters
      under the influence of stressors and exercise. Sympathetic innervation in
      secondary lymphoid organs plays a major role in immune regulation. Catecholamine
      released from the nerve terminal serves as the major mediator when bound to
      adrenergic receptors present on immunocompetent cells. Experiments using chemical
      and surgical denervation, catecholamine knock-out mice, and receptor antagonist
      and agonists revealed several important points. Sympathetic nerve activity is
      generally suppressive for the immunocompetent cells in the blood stream except
      neutrophils. Sympathetic activity facilitates detachment of T cells and NK cells
      from blood vessels without affecting functional adhesion molecule expression. Th1
      cells express more beta 2 adrenergic receptors than Th2 cells, indicating a
      greater influence of sympathetic activity on Th1 response. Sympathetic action was
      also shown to regulate the production of chemokines. Taken together, the
      sympathetic nervous system does not simply suppress the immune system but might
      help organize the immune response sequentially and spatially by modulating the
      distribution of immunocompetent cells.

PMID- 10919063
TI  - The scientific basis of practical strategies to maintain immunocompetence in
      elite athletes.
AB  - The functioning of the immune system is affected by stress. An accumulation of
      stress in elite athletes may lead to chronic immunosuppression and hence
      increased susceptibility to opportunistic infections. Therefore, athletes,
      coaches, and their medical support personnel are seeking guidelines to reduce the
      risk of illness, which, when it occurs, is likely to compromise training and
      competition performance. Training strategies to minimize the risk of
      immunosuppression need to consider the management of training volume and
      intensity, training variety to overcome monotony and strain, a periodised and
      graded approach to increasing training loads, and provision of adequate rest and
      recovery periods. In order to limit the effects of psychological stress, athletes
      should be taught self-management and coping skills. Benefit may be gained from
      monitoring athletes' responses to the psychological and psychosocial stresses of
      high-level training and competition. Nutritional considerations should emphasize
      the need for adequate intakes of fluid, carbohydrate, protein, and
      micronutrients. Limiting initial exposure when training or competing in adverse
      environmental conditions (heat, humidity, cold, altitude or polluted air) and
      acclimatizing where appropriate will reduce the effects of environmental stress.
      Other behavioral, lifestyle changes such as good hygiene practice, may limit
      transmission of contagious illnesses by reducing exposure to common sources of
      infection. Medical support including regular check ups, appropriate immunization,
      and prophylaxis may be particularly important for athletes who are at high risk
      of succumbing to recurrent infection.

PMID- 10919064
TI  - Upper respiratory tract infection in athletes: influence of lifestyle, type of
      sport, training effort, and immunostimulant intake.
AB  - Epidemiological evidence suggests that heavy acute or chronic exercise is related
      to an increased incidence of upper respiratory tract infections in athletes,
      while moderate exercise is believed to be protective. During the past years, many
      groups have investigated the association between changes within the immune system
      and exercise at different intensity levels. Although following strenuous
      exercise, some immunologic alterations were quite consistent and reproducible,
      e.g. neutrophilia, lymphopenia, and depression of natural killer cell activity,
      some findings were divergent or strongly dependent on the study design and
      athletes investigated. Lately, interesting results in the field of
      psychoneuroimmunolgy as well as new insights in the relationship between macro-
      and micronutrient and the immune system have brought up new fields of research
      interest. There is growing evidence that e.g. lifestyle factors, the coping with
      daily stress, and dietary behavior are important cofactors in the immune response
      to exercise. The present work gives a short review on the literature dealing with
      URTI in athletes with special reference to the above mentioned cofactors. In
      addition, the results of a recent investigation concerning training and
      associated lifestyle patterns in German athletes are presented.

PMID- 10919065
TI  - When world views collide: a commentary on home health care case-mix and patient
      outcomes.
AB  - The Health Care Financing Administration (HCFA) has developed a prospective
      payment system for home-health care that is primarily focused on cost
      containment. This new payment system results in a change in a case-mix for
      treatment that was more care-outcome based. The new case mix is compared to the
      old case mix with respect to research that is ignored regarding care outcome.

PMID- 10919066
TI  - Self-reported medication adherence and health status in late adulthood: the role
      of beliefs.
AB  - In this study, we explore the role of subjective beliefs in determining self
      reports of medication adherence and health status in 90 older adults (M age =
      71.7 years, SD = 7.44). Self-reported adherence was predicted by personal health
      locus of control beliefs, but not by medical factors nor beliefs regarding one's
      own health care professionals. Self-reported health was predicted by medical
      factors, perceptions of one's health care professional, and health locus of
      control. These results suggest that self-reported adherence is primarily a belief
      laden construct whereas self-reported health consists of both an objective
      assessment of health and a subjective belief-laden component. Exploratory
      analyses conducted on younger-old and older-old age groups indicated that medical
      factors may be less important to older-old adults' perceived health status than
      the younger-old adults.

PMID- 10919067
TI  - Motor skill learning of concentric and eccentric isokinetic movements in older
      adults.
AB  - Neuromuscular adaptation at the onset of resisted exercise can be observed as
      increases in torque and surface electromyography. The effect of learning the
      motor task has been hypothesized to contribute to these early increases,
      especially for older people. Thus, the purpose of this study was to investigate
      the facilitatory effects of practice on motor performance in older adults during
      short-term isokinetic training of the ankle dorsiflexors (DF). Twenty-eight men
      and women (M = 76.3 +/- 4.6 years) volunteered for a 2-week, 3-days/week strength
      training program. They were tested in a sitting position on a KinCom isokinetic
      dynamometer at 30, 90, and 180 degrees s-1 through 40 degrees of DF movement
      (concentric and eccentric contractions). Criterion curves of lever arm angle
      patterns were cross-correlated with subject-generated angle patterns, showing
      significantly better correlations on posttest versus baseline. Smoothness and
      proficiency of muscle contraction improved with practice by fewer hesitations in
      movement and increased ability to change between concentric and eccentric muscle
      contractions. Increased agonist electromyography and torque were hypothesized to
      be secondary to greater neural drive and/or synchronization of motor unit firing
      rate and/or recruitment during maximal voluntary contraction, improved
      coordination, and adapted neural control of concentric and eccentric muscle
      contraction.

PMID- 10919068
TI  - Computer testing of memory across the adult life span.
AB  - This study was designed to investigate whether differential experience with and
      reactions to computers among adults of different ages impact on adult age
      differences in computer memory testing. Participants were 141 community-dwelling
      adults, aged 18 to 87. Computer experience, computer anxiety, computer attitudes,
      and computer self-efficacy were measured in addition to several demographic
      items. Participants also completed a working-memory test on a desk top computer.
      Age was positively correlated with computer anxiety, but was not correlated with
      computer attitudes. In addition, older adults had less computer experience and
      lower computer self-efficacy. Computer experience, anxiety, and self-efficacy
      significantly mediated the relationship between age and computer-tested working
      memory performance. The results lend support to a model of cognitive aging that
      emphasizes the role of ability-extraneous factors in accounting for some of the
      observed age-related differences in computer-tested memory.

PMID- 10919069
TI  - Purchasing over-the-counter medications: the influence of age and familiarity.
AB  - This study examines the influence of age and type of over-the-counter (OTC)
      medications on decision-making processes leading to the selection of OTC
      medications. Manipulating type of OTC medication served as a way of examining
      subjects' familiarity with the decision domain. Thirty-six younger and thirty-six
      older adults answered questions regarding their OTC medication purchases, and
      completed a decision task in which they searched four computerized displays of
      product label information in order to select an antacid, a cold medication, a
      laxative, and a pain reliever. In general, older adults were slower to review
      information, more likely to have used OTC medications, and more organized in
      their searches for information. Specific to pair relievers, older and younger
      adults demonstrated similar information use and time to decision, and older
      adults specifically tailored the organization of their information searches when
      choosing pain relievers. Clearly, older adults selectively use product
      information on OTC medication packages, given adequate time to process
      information. Manufacturers' efforts directed at improving information
      availability should benefit older adults' decision processes.

PMID- 10919070
TI  - Justifications for ratings of old and young job applicants: an exploratory
      content analysis.
AB  - This study explored the content of 324 managers' written statements justifying
      their ratings of a hypothetical older or younger job applicant's interpersonal
      skills, economic worth, and likelihood of being interviewed for an upper level
      clerical position. Age-related concerns were more often elicited in rating the
      older applicant than the younger applicant, and importantly, most of these
      concerns were related to economic issues. Implications for these findings for
      research and practice are discussed.

PMID- 10919071
TI  - Design of new analogues of glutamic acid with a conformationally restricted
      structure.
AB  - Regioisomeric 3-carboxyisoxazolinyl prolines (CIP-A and CIP-B) and 3
      hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed
      for glutamate receptor activity. CIP-A [(+/-)-6] showed a convulsant activity
      evaluated in vivo on DBA/2 mice, higher than AMPA and similar to kainic acid. The
      eutomer of CIP-A [CIP-AS, (-)-6], obtained from (S)-3,4-didehydroproline,
      evidenced common stereochemical requirements with AMPA and kainic acid.

PMID- 10919072
TI  - Recombinant production of PIGF-1 and its activity in animal models.
AB  - In this paper we review current knowledge on placenta growth factor (PIGF) and
      summarise our data on its recombinant production in bacteria and its activity.
      PIGF and vascular endothelial growth factor (VEGF) are both angiogenic factors
      belonging to the platelet-derived growth factor (PDGF) family. PIGF is a dimeric
      glycoprotein which shares a number of biochemical and functional features with
      VEGF. The aminoacidic similarity between the two factors is high (about 50%) in
      the PDGF-like domain. By alternative splicing of the PIGF mRNA, three forms of
      PIGF protein are generated which are named PIGF-1, PIGF-2 and PIGF-3. We have
      focused our attention on form 1 of human PIGF (PIGF-1). A large quantity of
      active recombinant PIGF-1 has been obtained using a bacterial expression system.
      By optimising the fermentation and purification it was possible to produce about
      140 mg/l of culture of active PIGF-1, which is potentially suitable for a
      pharmaceutical use. The angiogenic activity of two different batches of bacteria
      derived PIGF-1 obtained in our laboratory was demonstrated in chick
      chorionallantoic membrane assays. Finally, in preliminary studies we have shown
      that bacteria-derived PIGF-1 has a protective effect against myocardial lesions
      induced by isoprenaline in rat and rabbit.

PMID- 10919074
TI  - Synthetic oligonucleotide combinatorial libraries and their applications.
AB  - The application of synthetic oligonucleotide combinatorial libraries is described
      in the studies of triplex DNA. A new method of selection of dispersed (beaded)
      oligonucleotide combinatorial libraries based on the use of streptavidin magnetic
      beads is presented. A combinatorial chemistry approach is also proposed for
      studies of polyaminooligonucleotides.

PMID- 10919073
TI  - Recent outcome in the field of distamycin-derived minor groove binders.
AB  - DNA minor groove binders represent a class of cytotoxic antitumor agents whose
      DNA sequence specificity may lead to a high selectivity of action. Tallimustine,
      benzoyl nitrogen mustard derivative of distamycin A, showed excellent antitumor
      activity in the preclinical tests, but as other minor groove binders, showed
      severe myelotoxicity. Novel nitrogen mustard derivatives of distamycin showing
      improved activity profile, have been identified recently. Moreover, a series of
      alpha-halogenoacrylamido derivatives of distamycin-like frames, in which the
      typical amidino moiety has been replaced with other moieties, was found to show
      cytotoxic and antitumor activity and cytotoxicity/myelotoxicity ratio improved
      significantly in comparison to tallimustine. The structural features of the
      alkylating moieties and binding frames, of distamycin and distamycin-like
      derivatives disclosed recently are discussed.

PMID- 10919075
TI  - Development of novel pain relief agents acting through the selective activation
      of the delta-opioid receptor.
AB  - A continuing effort in the development of non-peptide delta-opioid agonists as
      possible safe and effective pain relief agents has been seen in the last years.
      Novel potent and selective delta-opioid agonists based on the pirrolomorphinan
      framework have been designed, synthesised and biologically characterised in our
      laboratories. In particular, compound 7 (SB 235863) proved the concept that a
      selective delta-opioid agonist may be a valuable pain relief agent free of the
      unwanted side-effects usually associated with narcotic analgesics such as
      morphine.

PMID- 10919076
TI  - Alicyclic beta-amino acids: useful synthons in drug research.
AB  - The syntheses, transformations and some of the biological features of 2
      aminocyclopentanecarboxylic acid and related alicyclic beta-amino acids are
      discussed.

PMID- 10919077
TI  - Design and synthesis of melatonin receptors agonists and antagonists.
AB  - We review our work towards the design and synthesis of high-affinity melatonin (N
      acetyl-5-methoxytryptamine) agonist and antagonist compounds. High affinity
      melatonergic agonists were obtained by shifting the melatonin side chain from C3
      to N1 of the indole ring system. Conversely, by moving the side chain from C3 to
      C2 it was possible to obtain melatonin antagonist compounds, albeit of moderate
      affinity.

PMID- 10919078
TI  - Prolyl endopeptidase inhibitors.
AB  - Selective prolyl endopeptidase inhibitors were elaborated by modification of the
      structure of SUAM-1221, by using a CoMFA study and protein crystallography. The
      most active representatives of omega-(N-hetaryl)alkanoylprolylpyrrolidines,
      containing 2- or 3-methylene chain links have high activity (IC50 10(-9)-10(-11))
      and exhibit significant in vivo activities.

PMID- 10919079
TI  - Ligand-5-HT1A receptor interaction.
AB  - In the present paper the general structure and pharmacophore of some 5-HT1A
      receptor ligands are described. For several compounds (approximately 15) the
      intrinsic activity in lower lip retraction (postsynaptic, rat) and hypothermia
      (presynaptic, mice) tests was determined. For the identified functional
      presynaptic agonists and antagonists the influence on the brain serotonin level
      was examined. No direct correlation between the functional intrinsic activity and
      the influence on the level was observed. Molecular modelling revealed the
      possibility of the existence of different binding sites for different examined
      compounds.

PMID- 10919080
TI  - Statistical analysis on a series of glycine antagonists.
AB  - Quantitative structure-activity relationships of two series of glycine
      antagonists, pyrido[2,3-b]pyrazines and pyrido[2,3-b]pyrazine N-oxides, was
      performed using PLS (Projection on Latent Variables) and traditional physico
      chemical and topological descriptors. The effect of substitution on the
      heteroaromatic ring was investigated with the aim of further improving the
      affinity (expressed as pKi) of these derivatives towards the strychnine
      insensitive glycine binding site associated with the NMDA receptor. A significant
      model was obtained for both series of compounds. Structure-activity implications
      are discussed.

PMID- 10919081
TI  - From crystallographic data to the creation of a binding model with a receptor.
AB  - The basic model for glycine receptor site has been proposed based on the ligands
      incorporated spatially inflexible main skeleton. The search for compounds, which
      are selectively bound to the receptor, is now based on topological and/or
      stereochemical requirements and restrictions derived for the glycine binding
      site. IsoStar is the definitive database of experimental and theoretical
      information on non-bonded interactions. It has been designed to play a prominent
      role in the field of rational drug design. We applied IsoStar in our search for
      the model of glycine binding site of the NMDA receptor.

PMID- 10919082
TI  - Pyrrolo[2,1-d][1,2,3,5]tetrazinones deaza analogues of temozolomide with potent
      antitumor activity.
AB  - The title compounds, that hold the deaza skeleton of temozolomide, exhibited
      potent in vitro antiproliferative activity. An evaluation of such a biological
      activity indicates that the mode of action of these compounds differs from that
      of temozolomide and is also mechanistically unrelated to that of any known
      antitumor drug.

PMID- 10919083
TI  - Natural and synthetic polyamines: modulators of signalling proteins.
AB  - Ionotropic receptors are modulated allosterically by natural polyamines, such as
      spermine, and by polyamine derivatives, such as polyamine amides (e.g.
      philanthotoxin-343) and polymethylene tetraamines (e.g. methoctramine. Modulation
      can be either positive (potentiation) or negative (non-competitive antagonism of
      either open or closed channel receptor conformation). Photoaffinity labelling
      studies have identified a site close to the channel lumen on the nicotinic
      acetylcholine receptor Torpedo electroplax that is probably the allosteric site
      responsible for antagonism of the closed channel conformation of this receptor.

PMID- 10919084
TI  - Novel approaches in the rational design of antifungal agents of low toxicity.
AB  - This paper presents an overview of studies on novel strategies for the rational
      design of antifungal agents of low toxicity and overcoming the multidrug
      resistance (MDR) of fungi. This goal was achieved both due to the introduction of
      a novel target, glucosamine-6-phosphate synthase, as well as to the recognition
      of molecular basis of selectivity of action of amphotericin B derivatives.

PMID- 10919086
TI  - 4-Dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol-4-yl)butan-1
      ols: synthesis and evaluation of analgesic, anti-inflammatory and platelet anti
      aggregating activities.
AB  - A number of 4-dialkylamino-1-(5-substituted or unsubstituted 1-phenyl-1H-pyrazol
      4-yl)butan-1-ols 2a-n were synthesized and tested in vivo for anti-inflammatory
      and analgesic activities and in vitro for platelet anti-aggregating activity.
      Dimethylaminoderivatives 2b, e, g showed good analgesic activity; almost all of
      them had strong platelet anti-aggregating properties at a final concentration of
      1 x 10(-3) M; pyrazoles 2c, d, f-h showed weak anti-inflammatory activity.

PMID- 10919087
TI  - A novel synthesis of dibenzo[c,f]chromenes, dibenzo[c,h]chromenes and
      benzo[7,8]chromeno[3,4-f]isoindoles as antimicrobial agents.
AB  - Naphtho[2,1-b]pyranone (3) was allowed to react with arylmethylenemalononitriles
      to yield 4-amino-5-oxo-2-aryl-5H-dibenzo[c,f]chromene-3-carbonitriles (4a,b);
      with ethyl 3,4-dichlorobenzylidene cyanoacetate to furnish dibenzo[c,f]chromene
      (5) and with elemental sulfur in dioxane containing piperidine to give thieno[3,4
      d]naphtho[2,1-b]pyranone (6). Similarly, naphtho[1,2-b]pyranone (7) was reacted
      with arylmethylenemalononitriles and elemental sulfur to furnish
      dibenzo[c,h]chromenes (8) and thieno[3,4-d]naphtho[1,2-b]pyranone (10),
      respectively. Compound 10 underwent cycloaddition with N-arylmaleimides to yield
      benzo[7,8]chromeno[3,4-f]isoindoles (11a-c). Some of these compounds were
      screened in vitro for their antimicrobial activities.

PMID- 10919085
TI  - In vitro studies of the phototoxic potential of the antidepressant drugs
      amitriptyline and imipramine.
AB  - Amitriptyline and imipramine, two tricyclic antidepressant drugs, have been
      studied to evaluate their phototoxic potential using various models. Reactive
      oxygen species production was investigated. A negligible production of singlet
      oxygen was observed for both compounds whereas a significant production of
      superoxide anion was noted for amitriptyline in particular. Moderate red blood
      cell lysis under UVA light (365 nm) was induced in the presence of the two drugs
      at a concentration of 50 microM. Cellular phototoxicity was investigated on a
      murine fibroblast cell line (3T3). The two drugs were phototoxic causing cell
      death at a concentration of 100 microM and a UVA dose in the range of 3.3-6.6
      J/cm2. Furthermore, the two drugs photosensitized the peroxidation of linoleic
      acid, as monitored by the formation of dienic hydroperoxides. The presence of BHA
      and GSH, two free radical scavengers, significantly reduced the lipid oxidation
      photoinduced by the drugs, suggesting a predominant involvement of radical
      species. Finally, the involvement of nucleic acids in the phototoxicity mechanism
      was also investigated using a pBR322 plasmid DNA as a model.

PMID- 10919089
TI  - The past predicts a bright future for Indian science.

PMID- 10919088
TI  - The voltammetric study and determination of ramipril in dosage forms and
      biological fluids.
AB  - The voltammetric behavior of ramipril was studied using cyclic voltammetry,
      direct current polarography (DCt), differential pulse polarography (DPP) and
      alternating current polarography (ACt). Ramipril developed well-defined cathodic
      waves in Britton-Robinson buffers over the pH range 6-12. The waves were
      characterized as being diffusion-controlled, irreversible and partially affected
      by adsorption phenomenon. The diffusion-current constant (Id) was 1.24 +/- 0.02.
      The current-concentration plots were rectilinear over the range 10-50, 4-40 and
      0.16-12 micrograms/ml in the DCt, DPP and ACt modes, respectively, with a minimum
      detectability (S/N = 2) of 0.02 microgram/ml (4.8 x 10(-8) M) using the latter
      mode. The proposed method was successfully applied to the determination of
      ramipril in commercial tablets. Hydrochlorothiazide, which is frequently co
      formulated with ramipril, did not interfere with the assay. Furthermore, the
      proposed method was applied to the determination of ramipril in urine and plasma
      adopting the ACt technique. The percentage recoveries were 97.12 +/- 0.56 and
      94.97 +/- 0.62%, respectively. A pathway for the electrode reaction was proposed.

PMID- 10919090
TI  - Historical background of science and technology in the west and in India.

PMID- 10919091
TI  - Antiepileptic drug therapy in the twenty first century.
AB  - In the last 25 years, particularly the last decade, there have been many advances
      relating to all aspects of epilepsy i.e. pathophysiology, diagnosis,
      pharmacotherapy and surgical interventions. Noteworthy has been the progress in
      terms of understanding of the established antiepileptic drugs (AEDs) and
      introduction of several newer agents developed rationally, on the basis of now
      available information on the biochemical changes in the epileptic brain. Data is
      accumulating regarding the use of newer agents but they still need to stand the
      test of time. Many of the newer AEDs may offer a better tolerability because of
      favorable pharmacokinetic characteristics and minimal drug interactions. However,
      serious adverse events have been associated with felbamate and lamotrigine
      already and for other newer agents reliable and accurate data needs to be
      generated.

PMID- 10919092
TI  - Modulation of feeding and drinking behaviour by catecholamines injected into
      nucleus accumbens in rats.
AB  - Nucleus accumbens is proposed as one of the centers in the neural circuitry
      involved in the regulation of feeding and drinking behaviour in rats. Injection
      of dopamine and angiotensin-II into this nucleus has been documented to affect
      water and food intake in rats. Reports on the effect of intracerebral injection
      of catecholamines on feeding and drinking behaviour in animal models are
      conflicting. Therefore, in the present study the effect of adrenaline and
      noradrenaline injected into nucleus accumbens on food and water intake in rats
      was assessed. 24 h basal food and water intakes were recorded in Wistar rats and
      were found to be 12.3 +/- 0.46 g and 21.7 +/- 1.03 ml respectively. Stainless
      steel cannulae were implanted stereotaxically into the nucleus accumbens. Four
      different doses (0.1 microgram, 0.5 microgram, 1 microgram, and 2 micrograms) of
      adrenaline and noradrenaline were injected into the nucleus accumbens through the
      implanted cannulae in different group of animals and their 24 h food and water
      intakes were recorded following these injections. No change in food and water
      intake was observed following the administration of different doses of
      adrenaline. A significant increase in 24 h water intake reaching a maximum of
      28.88 +/- 1.45 ml at 1 microgram dose, without change in food intake was observed
      following administration of different doses of noradrenaline. The noradrenaline
      facilitated water intake was blocked when noradrenaline was injected following
      injection of phentolamine, an alpha-receptor blocker. The bilateral lesions of
      nucleus accumbens resulted in a significant and sustained inhibition of water
      intake (16.61 +/- 0.67 ml) without change in food intake. These observations
      suggest that noradrenaline facilitates water intake without affecting food intake
      when injected into the nucleus accumbens in rats and the dipsogenic effect of
      noradrenaline is mediated by alpha-receptors. Adrenaline does not affect these
      ingestive behaviours when injected into the nucleus accumbens in rats.

PMID- 10919093
TI  - Effect of glutamic acid and ketamine on morphine-induced analgesic response in
      rats.
AB  - Rats were treated with intraperitoneal injections of morphine (10 mg/kg) followed
      by glutamic acid (20 mg/kg.) and ketamine. (5 mg/kg). Pain thresholds were
      recorded as tail flick latencies for a period of 23 days and the mean area under
      curves calculated. Glutamic acid and ketamine, partially blocked the analgesic
      effects of morphine. Two types of effects were observed. In 4 animals, there was
      a partial blockade of the response, and in 2 animals there was a complete
      blockade followed by reversal in both the groups. It is suggested that two
      different mechanisms one excitatory and one inhibitory may be operating for the
      interaction of NMDA receptors with the opioid analgesic systems for modulating
      nociceptive responses.

PMID- 10919094
TI  - Protective role of estrogen in the neurodegenerative disorders.
AB  - Estrogen is an anabolic hormone of gonadal cells and it also modulates the growth
      and differentiation of non-gonadal cells like neuron/glia and protects them
      against the injury. The anabolic or protective actions of estrogen on the
      neuronal cells are mediated by the modulation of intracellular factors such as
      insulin like growth factor (IGF-I), tyrosine kinase A (Trk A), nerve growth
      factors (NGF) etc. It also modulates the action of neurotrophins which in turn
      regulate the synaptogenesis, synaptic plasticity and synaptic functions. By these
      actions estrogen prevents or slows down the neurodegenerative process.

PMID- 10919095
TI  - Antidotal efficacy of pyridinium oximes and cholineacetyltransferase inhibitors
      against organophosphorus intoxication in rodents.
AB  - In an attempt to develop effective antidote against organophosphorus
      intoxication, some new imidazole-pyridinium mono-oximes, long chain pyridinium
      mono-oximes and cholineacetyltransferase inhibitors were synthesised. These
      compounds were evaluated for their in vivo therapeutic protection and
      neuromuscular function studies in rodents. The results indicate that SPK-series
      oximes may be useful against sarin poisoning without any beneficial effect
      against VX (O-Ethyl S-2-NN-diisopropylaminoethyl methylphosphonofluoridate)
      intoxication. The cholineacetyltransferase (ChAT) inhibitors may not be of any
      help against any of the OP compounds studied in this study.

PMID- 10919096
TI  - An observational study on neurobehavioural effects of acute oxydemeton-methyl
      (insecticide and acaricide) exposure in rats.
AB  - Oxydemeton-methyl, an organophosphate insecticide and acaricide produced decrease
      in the exploratory behaviour and prolongation of barbitone sodium-induced
      hypnosis after intermittent aerosol spray inhalational exposure for 1 h in rats
      compared to the saline control group. Further, CD50 +/- S.E.M. value for
      pentylenetetrazole (PTZ) and CI50 +/- S.E.M. value for electroshock (i.e. the
      dose of PTZ and intensity of electroshock producing positive seizure response in
      50% of rats) were significantly decreased by acute exposure to oxydemeton-methyl
      compared to that of saline control group. The study has established the central
      nervous system depressant effect and proconvulsant potential of oxydemeton-methyl
      which is widely used by the agricultural workers in the form of field spray.

PMID- 10919097
TI  - Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced
      liver damage in rats.
AB  - The effect of aqueous leaf extract of Azadirachta indica (A. indica) was
      evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was
      produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver
      damage was evidenced by elevated levels of serum aspartate aminotransferase
      (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT)
      and by histopathological observations of liver sections. Aqueous A. indica leaf
      extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels
      of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to be
      reduced as observed macroscopically and histologically.

PMID- 10919098
TI  - A study of hypoglycaemic effects of Azadirachta indica (Neem) in normaland
      alloxan diabetic rabbits.
AB  - Hypoglycaemic effect was observed with Azadirachta indica when given as a leaf
      extract and seed oil, in normal as well as diabetic rabbits. The effect, however,
      was more pronounced in diabetic animals in which administration for 4 weeks after
      alloxan induced diabetes, significantly reduced blood glucose levels.
      Hypoglycaemic effect was comparable to that of glibenclamide. Pretreatment with
      A. indica leaf extract or seed oil administration, started 2 weeks prior to
      alloxan, partially prevented the rise in blood glucose levels as compared to
      control diabetic animals. The data suggests that A. indica could be of benefit in
      diabetes mellitus in controlling the blood sugar or may also be helpful in
      preventing or delaying the onset of the disease.

PMID- 10919099
TI  - Mechanism of action of 6, 7, 8, 9, 10, 12-hexahydro-azepino-[2, 1-b] quinazolin
      12-one-(RLX)--a novel bronchodilator.
AB  - The present study presents a mode of action profile of RLX (6, 7, 8, 9, 10, 12
      hexahydro-azepino-[2, 1-b]-quinazoline-12-one) a bronchodilator obtained by the
      chemical modification in the molecule of alkaloid vasicine (Ex: Adhatoda vesica).
      The effect of RLX (p.o.) was observed on: (a) mast cell degranulation, (b)
      release of histamine and prostaglandin E (PGE), (c) 45Ca uptake and (d)
      activities of cAMP phosphodiesterase (PDEase) and lipoxygenase enzymes in
      mesenteries/peritoneal mast cells/lung tissue homogenates in rats under systemic
      anaphylaxis. RLX (10 and 20 mg/kg) inhibited antigen-induced mast cell
      degranulation and released of histamine from target tissues. An increased outflow
      of PGE (lungs) and an inhibited 45Ca uptake (peritoneal mast cells) were noted.
      Lung PDEase and lipoxygenase activities were decreased. These results suggested
      that RLX could be acting like disodium cromoglycate and aminophyline with
      additional attributes its oral efficacy and long duration of action.

PMID- 10919100
TI  - Effect of HD-03--a herbal formulation in galactosamine-induced hepatopathy in
      rats.
AB  - The effect of HD-03 a herbal preparation was studied on galactosamine (400 mg/kg
      b.wt., i.p.) induced hepatotoxicity in rats. Animals were pre-treated for 14 days
      with HD-03 and compared against untreated group for SGPT, SGOT, serum bilirubin
      and liver glycogen. Histopathology of liver lobes was considered to evaluate the
      extent of hepatic injury induced by galactosamine. These were reversed by HD-03
      pre-treatment. HD-03 provided convincing evidence of hepatoprotection against
      galactosamine induced hapatotoxicity.

PMID- 10919101
TI  - Effect of occupation on lipid peroxidation and antioxidants' status in masons.
AB  - Effect of occupation on haematological factors, lipid peroxidation and
      antioxidants' status was studied in masons and compared with normal subjects. Red
      blood corpuscles (RBC), haemoglobin (Hb), Vitamin C, Vitamin E, beta-carotene
      levels and glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and
      catalase (CAT) activities decreased. Thiobarbituric acid reacting substances
      (TBARS) level increased. Occupational exposure to cement increased lipid
      peroxidation but decreased antioxidants' levels in masons. Increased lipid
      peroxidation seems to be responsible for the reduction in RBC and Hb.

PMID- 10919102
TI  - Task related changes in ERP auditory vs visual tasks.
AB  - P3 component of event related potentials have been studied in relaxed state of
      mind. Changes in P3 latency and amplitude are expected if measured after a
      rigorous mental exercise. The event related potentials (ERP) were measured in 20
      normal male subjects aged between 18 and 22 years. ERP was recorded twice in each
      subject before and after the administration of a mental task. The auditory mental
      task comprised of repeating in reverse order string of random digits read out to
      the subject at a uniform speed of 1 per second. The visual task comprised reading
      laterally inverted type written text. Each subject had to undergo 2 sessions in
      separate sittings. The latency and amplitude of P300 recorded before and after
      the task were compared statistically using Students' unpaired t-test. There was
      significant increase in P3 latency following both visual and auditory tasks
      (auditory task: before 330 +/- 24.43 msec and after 342.9 +/- 27.66 msec,
      similarly visual task: before 333.2 +/- 26.66 msec and after 345.65 +/- 26.56
      msec). All other ERP waves latency and amplitude changes were insignificant.

PMID- 10919103
TI  - Effects of different levels of coconut fiber on blood glucose, serum insulin and
      minerals in rats.
AB  - The effect of neutral detergent fiber (NDF) from coconut kernel (Cocos nucifera
      L) in rats fed 5%, 15% and 30% level on the concentration of blood glucose, serum
      insulin and excretion of minerals was studied. Increase in the intake of fiber
      resulted in significant decrease in the level of blood glucose and serum insulin.
      Faecal excretion of Cu, Cr, Mn, Mg, Zn and Ca was found to increase in rats fed
      different levels of coconut fiber when compared to fiber free group. The result
      of the present investigation suggest that inclusion of coconut fiber in the diet
      results in significant hypoglycemic action.

PMID- 10919104
TI  - Anti-inflammatory activity of sodium pyruvate--a physiological antioxidant.
AB  - The anti-inflammatory activity of sodium pyruvate was evaluated in acute and
      chronic models of inflammation in rats. Oral administration of sodium pyruvate at
      three different dose levels of 125, 250 and 500 mg/kg body weight significantly
      inhibited the carrageenan induced acute paw edema in a dose dependent manner. The
      effect of 500 mg/kg sodium pyruvate was comparable to that of 12.5 mg/kg of
      standard diclofence. In Freund's adjuvant arthritis model, oral administration of
      sodium pyruvate at the submaximal dose of 250 mg/kg once daily upto one week
      before Freund's adjuvant injection and immediately by the same route on the 7th
      day of adjuvant injection significantly reduced the edema at 18 hours after the
      challenge. The treatment was continued for 14 days thereafter in two divided
      doses of 125 mg/kg in the morning and 125 mg/kg in the evening. Sodium pyruvate
      showed significant anti-inflammatory activity at the 14th day (chronic phase)
      also. To conclude, sodium pyruvate exhibited significant anti-inflammatory
      activity in both the models of inflammation which could be attributed to its
      antioxidant properties.

PMID- 10919105
TI  - Acute noise-induced alterations in the immune status of albino rats.
AB  - The effect of acute noise induced changes on the immune functions of albino rats
      was studied. Cell mediated immunity was assessed by Leukocyte migration
      inhibition index (LMI) and humoral immunity by estimating antibody titre. The
      organ weight of spleen, thymus, adrenal and lymph node was noted, the cell count
      of spleen and thymus was enumerated and plasma corticosterone level was
      estimated. A significant increase in the plasma corticosterone level, thymus
      weight and cell count along with significant decrease in the antibody titre,
      spleen weight and cell count was observed in noise stressed animals. No
      significant changes were observed in the LMI and organ weight of adrenal and
      lymph node in these animals. Our study shows acute noise to be a potent stressor
      causing definite alterations in the immune functions of the albino rats.

PMID- 10919106
TI  - Patterns of prescriptions and drug use in two tertiary hospitals in Delhi.
AB  - The study was carried out to assess prescribing trends in outpatients at Dr. R.P.
      Centre for Ophthalmic Sciences (RPC) and other OPD's of All India Institute of
      Medical Sciences (AIIMS) and Safdarjung hospitals, two premier hospitals in
      Delhi. Prescriptions of 500 patients were audited and analysed under heads of
      average number of drugs per patient, percentages of drugs prescribed by generic
      name, antibiotics, injections, drugs from WHO recommended essential drug list,
      availability of drugs etc. using WHO basic drug indicators. Prescription analysis
      showed that 75 to 95% drugs were prescribed from essential drug list. The average
      number of drugs per prescription was 1.42 to 4.07. Percentage of antibiotics
      prescribed varied from 14.39% to 22.28%. The use of injections was from nil to
      4.4%. Availability of drugs was however, not satisfactory. Though maximum drugs
      were prescribed from essential drug list, the results indicate that there is a
      considerable scope for improving prescribing habits according to rational drug
      use and to provide a feed back to hospital authority for making maximum number of
      drugs available to the patients.

PMID- 10919107
TI  - Adverse drug reactions to fluoroquinolones in pediatric patients in a tertiary
      care hospital.

PMID- 10919108
TI  - Pulmonary functions in Punjabi pregnant women.

PMID- 10919109
TI  - Effect of environmental lead pollution on haemoglobin and erythrocyte ALAD
      activity.

PMID- 10919110
TI  - Woes of researchers in India.

PMID- 10919111
TI  - [One against three. The physician is helpless when pitted against federal
      attorney, the board and the media].

PMID- 10919112
TI  - [History of Ophthalmological Clinic, University Erlangen-Nurnberg (Part I).
      Dedicated to professor Dr.G.O.H. Naumann on his 65. birthday].

PMID- 10919113
TI  - [Laudatio. Dedicated to Professor Dr. G.O.H. Naumann on his 65th birthday].

PMID- 10919114
TI  - Changing patterns in the surgery for retinal detachment: 1929 to 2000.
AB  - PURPOSE: To examine the development of surgery for retinal detachment in this
      century and to determine whether the countless innovations and modifications fall
      into a recognizable pattern. MATERIALS AND METHODS: The authors, whose entire
      professional life has been devoted to the treatment of retinal detachment, have
      made a retrospective analysis of their experience in the field of retinal
      surgery. They have reviewed their notes of the annual meetings of the Retina
      Society, the Retinological Society, and the biennial meetings of the Gonin Club,
      all of which they attended, and augmented this with an in-depth review of the
      literature. RESULTS: Four conceptual advances by Jules Gonin, Bengt Rosengren,
      Ernst Custodis and Robert Machemer and countless modifications by a new category
      of specialists, the retinal surgeons, merge into two general patterns for the
      surgical repair of retinal detachment. The one is a local operation confined to
      closing the retinal breaks, the other is a circumferential operation intended to
      barricade the breaks and the peripheral retina. Both were extraocular operations.
      The more recent intraocular procedures, pneumatic retinopexy and vitrectomy,
      although apparently unique, nevertheless, fall into one or the other pattern.
      CONCLUSIONS: Surgery for retinal detachment has improved the prognosis from 0%
      before 1929 to near 100%. Reducing morbidity and the incidence of reoperation
      remain a worthy objective for the coming century.

PMID- 10919115
TI  - [Synopsis of various electrophysiological tests in early glaucoma diagnosis-
      temporal and spatiotemporal contrast sensitivity, light- and color-contrast
      pattern-reversal electroretinogram, blue-yellow VEP].
AB  - BACKGROUND: Of the three glaucoma-defining criteria intraocular pressure, optic
      nerve damage, and visual field damage, the latter is a late symptom. Therefore,
      in order to improve an early sensory diagnosis, new tests are necessary. It is
      the aim of the present paper to test new sensory methods, to rank them in an
      order of sensitivity, and to base them on possible pathophysiological mechanisms.
      PATIENTS AND METHODS: The tests were carried out in subjects of the Erlangen
      Glaucoma registry: Normals, patients with ocular hypertension, and patients with
      open-angle glaucoma without or with field defects. The tests are designed to
      preferentially probe the function of different groups of ganglion cells.
      Psychophysical methods: Temporal contrast sensitivity in a ganzfeld as "Erlangen
      flicker test" and spatio-temporal contrast sensitivity to test Magno-cell
      function. Electrophysiological methods: Pattern-reversal electroretinogram with a
      luminance-contrast pattern to test Magno-cell function, color-contrast pattern
      electroretinogram for Parvo-cell function, and blue-on-yellow visual evoked
      potential to test the "blue-sensitive" pathway. RESULTS: The most sensitive test
      is the temp.CS, it is significantly reduced in OHT (p < 0.01). The spatio-temp.CS
      is reduced in perimetric stages (p < 0.01). The BY-VEP is altered in the
      preperimetric stage (p < 0.01), the PR-ERG in perimetric stages (p < 0.01). The
      CC-ERG is reduced in even later stages. These results are in agreement with the
      hypothesis that tests selective for non-redundant neurons are of early diagnostic
      value. Multivariate analyses increase the early diagnostic value when different
      functions are tested in combination. CONCLUSIONS: When a particular test is
      taylored to the the special needs of certain groups of ganglion cells sensory
      defects can be observed before the occurrence of optic-nerve damage (OHT). The
      most sensitive psychophysical test is the "Erlangen flicker test" which is a
      screening test selective for M cells. The most sensitive electrophysiological
      test is the BY-VEP testing the blue-sensitive ganglion cells.

PMID- 10919116
TI  - [Cataract surgery in 79 patients with relative anterior microphthalmus (RAM): a
      review of anatomy, associated pathology and complications].
AB  - BACKGROUND: Naumann has coined the term relative anterior microphthalmus (RAM)
      for eyes with a dysproportional small anterior segment but no further
      malformation. Those eyes are characterized by corneal diameters of < 11 mm and
      total axial length of > 20 mm. PATIENTS AND METHODS: To evaluate and define
      morphometrical data and risk factors for cataract surgery in patients with
      relative anterior microphthalmus (RAM) 112 cataract operations of 79 patients
      with RAM were analysed. Associated ocular pathology (such as glaucoma, previous
      surgical interventions, etc.) and complications of cataract surgery were
      recorded. RESULTS: Average corneal diameter was 10.7 +/- 0.34 mm, AC-depth was
      2.20 +/- 0.49 and average lens thickness 5.05 +/- 0.45 mm. Fifty five percent of
      the patient revealed myopic refraction. There was a high incidence of glaucoma
      (77%), cornea guttata (46.6%) and Pseudoexfoliation syndrome (16%) in the RAM
      group. Sixty percent of patients previously underwent glaucoma surgery. After
      cataract surgery 51.2% of patients achieved a visual acuity of > 0.5; 69.8% >
      0.4. The IOP was preoperatively 16.5 +/- 5.8 mm Hg (with 1.3 +/- 1.4
      antiglaucomatous drugs). Postoperatively IOP dropped significantly to 13.6 +/-
      3.2 mm Hg (with significant reduction of treatment (0.6 +/- 1.0) (p < 0.01). The
      anterior chamber depth deepened from 2.42 +/- 0.47 mm to 3.33 +/- 0.72 mm.
      CONCLUSIONS: The special anatomical situation in RAM is responsible for the high
      incidence of glaucoma and postoperative complications after cataract surgery.
      Cataract surgery helps not only to restore vision but also facilitates handling
      and regulation of intraocular pressure.

PMID- 10919117
TI  - [Dysgenetic changes of the angle of the anterior chamber in patients with
      glaucoma or suspected glaucoma acquired before age 40].
AB  - OBJECTIVE: The aim of this study is to determine percentage and degree of
      dysgenetic changes in the chamber angle in glaucoma suspects and in patients who
      acquired glaucoma before the age of fourty and to compare the primary
      classification with the classification after reexamination. PATIENTS AND METHODS:
      200 eyes of 104 patients (59 males, 45 females, 0-40 yrs old (median 29) at time
      of detection) could be examined or reexaminded by gonioscopy and photography with
      the CGA-1 goniolens. The angles were documented by drawing and by
      goniophotography. The different features of dysgenesis served to establish a
      point-scale. RESULTS: Out of 200 eyes in 24 eyes (12%) a slight, in 81 (40.5%) an
      intermediate and in 49 (24.5%) a severe goniodysgenesis was found. By
      reexamination the dysgenesis rate rose from 48 to 77%. CONCLUSIONS: The high
      frequency of dysgenetic changes in the chamber angle of glaucoma patients
      affected under the age of fourty suggests, that in this age group developmental
      glaucoma is predominant and has to be separated as a special entity from POAG.
      Two questions arise: 1. Were these dysgenetic changes overlooked most of the time
      in the newer genetic studies of patients with GLC1A, or, if not, 2nd: Do glaucoma
      suspects and patients with open angle glaucomas before the age of 40 with and
      without dysgenetic changes belong to groups with different glaucoma genes, the
      "with" to genes IRID 1 and IRID 2 and the "without" to genes GLC1A to GLC1F?

PMID- 10919118
TI  - [Pseudoexfoliation (PEX) syndrome and intraoperative complications in cataract
      surgery].
AB  - BACKGROUND: Conventional wisdom holds that pseudoexfoliation syndrome (PEX) leads
      to an increased risk during cataract surgery with regard to zonular dialysis,
      rupture of the posterior capsule and luxation of the lens into the vitreous as a
      consequence of insufficient zonules. The present study is focused on the impact
      of pseudoexfoliation syndrome on the outcome of cataract surgery. PATIENTS AND
      METHODS: We included in a prospective study 1210 patients which underwent
      cataract surgery (phacoemulsification) and implantation of a posterior chamber
      lens in our department from October 1997 until June 1999. The course of surgery,
      relevant associated diagnoses, and intraoperative complications are described.
      The patients were divided in a PEX-group and non-PEX-group. RESULTS: There was no
      difference in the percentage of glaucoma patients between the PEX-group (16.2%)
      and non-PEX group (17.7%). There were statistically significant more women in the
      PEX-group and the average age was higher. Intraoperative complications, such as
      rupture of the posterior capsule, zonular dialysis and displacement of the lens
      into the vitreous body were similar in the two groups. CONCLUSION: This present
      study shows, that modern cataract surgery makes it possible to achieve good
      operative results, even in risk patients. Preoperative presence of PEX had no
      influence on the complication rate of cataract surgery.

PMID- 10919120
TI  - [Can fixation disparity be detected reliably by measurement and correctional
      techniques according H.J. Haase (MKH)?].
AB  - BACKGROUND: The theory of the "Measuring and Correction Methods of H.-J. Haase"
      (MCH) states that a small misalignment of one eye, called fixation disparity,
      indicates a difficulty in overcoming a "vergence position of rest" that is
      different from ortho position. This difficulty, so the theory, can cause
      asthenopic complaints, such as headaches, and these complaints can be relieved by
      prisms. The theory further claims that fixation disparity can be ascertained by a
      series of tests which depend on the subject's perception. The tests most decisive
      for the diagnosis of a so-called fixation disparity type 2 consist of stereo
      displays. The magnitude of the prism that allows the subject to see the test
      configurations in symmetry is thought to be the one that corrects the "vergence
      position of rest". METHODS: Nine subjects with healthy eyes in whom a "fixation
      disparity type 2" had been diagnosed were selected for the study. Misalignment of
      the eyes was determined according to the principle of the unilateral cover test.
      Targets identical for both eyes were presented on the screen of the Polatest E.
      Then, the target was deleted for one eye and the ensuing position change of the
      other eye was measured, using the search coil technique. This test was performed
      both with and without the MCH prism. RESULTS: In all 9 subjects the misalignment
      was less than 10 minutes of arc, i.e. in the range of normal fixation
      instability. Averaging across the 9 subjects, the deviation of the eye
      (misaligned according to MCH) was 0.79 +/- 3.45 minutes of arc in the direction
      opposed to that predicted by the MCH, a value not significantly different from
      zero. The MCH prism elicited a fusional vergence movement the magnitude of which
      corresponded to the magnitude of the MCH prism. CONCLUSION: Ascertaining fixation
      disparity with the MCH is unreliable. Accordingly, it appears dubious to correct
      a "vergence position of rest" on the basis of the MCH.

PMID- 10919119
TI  - [Regression analysis of corneal endothelium after nonmechanical penetrating
      keratoplasty].
AB  - PURPOSE: The corneal endothelial cell density is a crucial parameter for the pump
      function and the transparency of grafts after penetrating keratoplasty (PK). The
      purpose of this study was to assess corneal endothelial cell density with
      different regression models after nonmechanical penetrating keratoplasty and to
      check for differences between diagnoses and two different storage methods.
      PATIENTS AND METHODS: Two-hundred ninety-six eyes (195 keratoconus, 101 Fuchs'
      dystrophies, 148 each with short-term preserved and organ-cultured donor corneas)
      of 268 patients were included in this prospective study. Donor and recipient
      trephination was performed using nonmechanical trephination technique with the
      excimer laser 193 nm along metal aperture masks from the epithelial side. The
      time course of the endothelial cell density (specular microscope EM 1100, TOMEY,
      Erlangen) after PK was assessed. Endothelial cell density was first analyzed in a
      cross sectional manner at the 3, 6, 12, 18 and 24 months follow-up and, secondly
      in a longitudinal manner with linear, polynomial and exponential regression
      models in the sense of minimizing the residuum (distance between observed and
      predicted endothelial cell count). The mean donor postmortem time was 10.3 +/-
      6.8 hours for short-term-preserved and 19.6 +/- 9.5 hours for organ-cultured
      corneas (p < 0.0001). The storage time was 63 +/- 49 and 19 +/- 7 days (p <
      0.0001), respectively. RESULTS: In a cross section, overall mean endothelial cell
      density decreased from 2145 +/- 599 cells/mm2 at the 3 months to 1751 +/- 605
      cells/mm2 at 2 years follow-up (p > 0.05). Cell density did not differ
      significantly between different diagnoses or storage methods at any postoperative
      stage. In a longitudinal section, the linear regression model estimated an annual
      decrease of 214 cells/mm2. In a polynomial model the decrease expressed by a
      tangent to the regression line at 24 months was 175 cells/mm2. The exponential
      regression model yielded a relative decrease of 9.5% annually. The so-called
      residuum as a measure for the validity of the regression model was maximal in the
      linear and minimal in the exponential estimate. With keratoconus and short-term
      preserved donor material the endothelial cell loss was less in the regression
      analysis. CONCLUSION: During the first two years after nonmechanical trephination
      in PK, a non-significant decrease in endothelial cell density was observed. The
      exponential regression model seems to be predestinated for analysis of the time
      course of corneal endothelium in a longitudinal manner. The annual cell loss
      ranged around 9.5% without significant differences between diagnoses and storage
      methods.

PMID- 10919121
TI  - [Latent TGF-beta 1 binding protein (LTBP-1); a new marker for intra-and
      extraocular PEX deposits].
AB  - BACKGROUND: Pseudoexfoliation (PEX) syndrome is a generalized process of the
      extracellular matrix characterized by the accumulation of an abnormal
      pathognomonic material in various intraocular and extraocular tissues. Whereas
      the intraocular manifestations can be directly diagnosed by biomicroscopic
      observations, the extraocular manifestations can presently only be diagnosed by
      electron microscopic methodology. In order to better evaluate the distribution
      and precise localization of PEX deposits in the various organ systems, we
      searched for a relatively specific immunohistochemical marker for PEX material on
      the light microscopic level. MATERIAL AND METHODS: Eyes and tissue specimens of
      various organ systems (skin, heart, lungs, liver, kidney, abdominal aorta,
      cerebral artery, plexus choroideus, meninges) obtained from 4 organ donors with
      ocular PEX syndrome and age-matched control tissues were investigated by electron
      microscopy and immunohistochemistry using antibodies against various elastic
      microfibrillar components. RESULTS: Out of a panel of antibodies tested, the
      immunolabeling of both intra- and extraocular PEX deposits with antibodies
      against latent TGF-beta 1 binding protein (LTBP-1) was particularly prominent. In
      addition to the known intraocular sites of PEX material accumulations, focal
      plaque-like LTBP-1 positive deposits could be observed in the conjunctival
      stroma, optic nerve meninges, skin, heart muscle, lungs, kidney as well as in the
      adventitia of the aorta and cerebral artery from donors with PEX syndrome; such
      plaque-like deposits positive for LTBP-1 were not present in the control tissues.
      Transmission electron microscopy confirmed the presence of typical fibrillar PEX
      aggregates in the respective tissues. CONCLUSIONS: Antibodies against LTBP-1
      provide a new and relatively specific marker for PEX deposits both in intraocular
      and extraocular locations. Systematic screening of PEX accumulations in a larger
      number of extraocular tissue specimens obtained from PEX patients may help to
      elucidate the functional implications and consequences of the systemic
      manifestations.

PMID- 10919122
TI  - [Primary iris stromal cyst with unusual symptoms in an adult].
AB  - BACKGROUND: Most epithelial cysts of the anterior chamber ("iris stromal cysts")
      occur after penetrating ocular injuries and represent secondary epithelial
      ingrowth. Primary iris stromal cysts are less common and mostly congenital.
      Acquired primary iris stromal cysts in adults are extremely rare and cause less
      often symptoms than congenital cysts. PATIENT: A 41-year old patient presented
      with sudden loss of visual acuity, epiphora and photophobia of his right eye. A
      large iris cyst was found in the nasal lower quadrant of the anterior chamber. It
      had not been present 3 years before when the patient was last seen by an
      ophthalmologist. There was no history of trauma and no signs of preceding ocular
      injury at slit-lamp examination. The cyst was surgically removed by
      iridocyclectomy. Postoperatively the patient developed cataract and macular
      edema. A phacoemulsification with posterior chamber lens implantation as well as
      a systemic treatment with steroids and acetazolamide were necessary. Until now,
      two years after surgery, the cyst did not recur. CONCLUSIONS: Primary iris
      stromal cysts also occur in adults. In contrast to previous reports the cyst of
      our patient has caused acute symptoms.

PMID- 10919123
TI  - [Diffuse retinal pigmented epitheliopathy associated with systemic corticosteroid
      therapy].
AB  - BACKGROUND: It is well known that topical as well as systemic treatment with
      corticosteroids may have ocular side effects. The most common are the development
      of cataract and increase of intraocular pressure, however, alteration of the
      retinal pigment epithelium may also occur. PATIENT: A 64-year old male
      experienced a progressive decrease of visual acuity over a time period of 6
      weeks. Ophthalmologic examination revealed a severe diffuse retinal pigment
      epitheliopathy with serous detachment of the neurosensory retina. This patient
      was treated with systemic methylprednisolone for chronic glomerulonephritis.
      After cessation of the treatment with systemic corticosteroids visual acuity
      improved and the serous retinal detachment resolved. CONCLUSION: Ophthalmologic
      examination including biomicroscopy of the retina is recommended on a regular
      basis for patients treated with systemic corticosteroids. With development of
      pigment epithelial changes steroids should be reduced or discontinued if
      possible.

PMID- 10919124
TI  - [Factors associated with changes in microalbuminuria during antihypertensive
      treatment].
AB  - BACKGROUND: The objective of the present study was to analyze the factors related
      with changes of microalbuminuria during antihypertensive treatment in patients
      with essential hypertension. METHODS: One hundred and six patients (57 men, mean
      age 40.8 [SD 6.6] years) never treated with antihypertensive treatment were
      included. At the beginning and after one year, blood pressure biochemical profile
      and urinary albumin excretion (UAE) were measured. After the initial evaluation,
      53 patients received angiotensin converting enzyme inhibitors (ACEi) and 53 beta
      blockers (BB). Hydrochlorothiazide was added to achieve the blood pressure target
      < 140/90 mmHg. RESULTS: The average of UAE was 32.1 (43.1) mg/24 h, and 41 (39%)
      patients had microalbuminuretics. After 12 months of treatment, a significative
      fall of systolic BP (-20.6 [8.03] mmHg, p < 0.001), and diastolic BP (-14.18
      [10.34] mmHg, p < 0.001) were observed, whereas baseline glucose increases (3.08
      [11.07] mg/dl, p = 0.006). The changes of UAE were only related with the baseline
      UAE values. Neither, age, sex, baseline diastolic BP and changes in diastolic BP
      were significantly related with the changes in UAE. In spite of similar mean BP
      reduction (medial BP 17.4 [10.9] vs 14.8 [10.4] mmHg), UAE only was reduced in
      patients treated with ACEi (LogUAE: 0.203 [0.872] mg/24 h; p < 0.04). In
      addition, in patients treated with BB a significative increase in baseline
      glucose (4.4 [12.3] mg/dl; p = 0.013) and uric acid (1.18 [4.18]; p = 0.031) were
      observed. CONCLUSIONS: In patients with essential hypertension, changes in
      microalbuminuria depends of the initial UAE values and the kind of
      antihypertensive treatment. ACEi produced higher UAE reduction and lower
      derangement of the glucose metabolism than BB.

PMID- 10919125
TI  - [Coinfection with hepatitis G virus in chronic hepatitis C. Response to treatment
      with interferon alpha].
AB  - BACKGROUND: It is thought that the cytopathic effect of HGV is not important.
      Nevertheless, the cytopathic effect on liver is less known in the cases of co
      infection with HCV. The aim was to study the prevalence of co-infection in
      patients with chronic hepatitis C (CHC) and to analyse the clinical
      epidemiological and histological data and the interferon (IFN) response. PATIENTS
      AND METHODS: We included 180 patients with CHC and the HGV-RNA was determined.
      RESULTS: The prevalence of co-infection was 12.2% (n = 22). No statistical
      differences were observed between the non co-infected and co-infected groups with
      regard to the age, sex, mechanism of transmission and alcohol abuse. Also, there
      were no differences in the hepatic biochemical, no organ-specific antibodies,
      histological lesions and Knodell index. The HCV biochemical response (BR) and
      virological response (VR) after 6 months post-IFN were the same in both groups
      (HGV negative: BR = 29%, VR = 12%; HGV positive: BR = 22%, VR = 18%). HGV was
      determined after 6 months posttreatment in the co-infected group (first cycle of
      IFN, n = 22; second cycle of IFN, n = 9): 12 (55%) were HGV-RNA negative and 5
      (23%) HCV-RNA negative, (p = 0.021). When we compared the BR vs VR in this group,
      there were 12 HGV-RNA negative but only two had BR (NS). On the contrary, the BR
      was related to HCV-RNA negative (p = 0.023). CONCLUSION: The prevalence of HGV co
      infection is important in our area (12.8%). The HGV does not increase the
      pathogenicity of HCV and does not change the IFN response, although the HGV is
      more IFN sensible than HCV. The determination of HGV is not necessary in patients
      with HCV.

PMID- 10919126
TI  - [Analysis of internal notices to the emergency team of the medical area at a
      general hospital].
AB  - OBJECTIVE: To study the frequency and characteristics of the hospitalized
      patients medical emergencies. PATIENTS AND METHODS: We have collected daily the
      notice to the emergency room from patients hospitalized and we have analyzed the
      clinical and epidemiological characteristics. RESULTS: Three hundred forty-one
      notices were recorded. The daily mean was higher on holidays. There were mostly
      medical problems (78%). Complementary explorations were performed in the 44% of
      the patients, and in the 77% the treatment was changed. CONCLUSIONS: The in
      patient emergencies account for an important charge of work for the emergency
      team and involve important diagnosis and therapeutic decisions.

PMID- 10919127
TI  - [Predictive value of microalbuminuria].

PMID- 10919128
TI  - [Hepatitis G virus (HGV). Much ado about...].

PMID- 10919129
TI  - [The case of Bezwoda: fraud in oncologic research. Consequences and some
      thoughts].

PMID- 10919130
TI  - [Primary Sjogren's syndrome and lymphatic proliferation].

PMID- 10919131
TI  - [Estrogens and Alzheimer's disease: rationale, promises, and facts].

PMID- 10919132
TI  - [Tuberculosis in health personnel. Difficult diagnosis in Spain].

PMID- 10919133
TI  - [Variability of the classification dipper/non-dipper in the hypertensive
      patient].

PMID- 10919134
TI  - [Energy expenditure and anorexia nervosa].

PMID- 10919135
TI  - [Bilateral salpingitis caused by Haemophilus influenzae in a patient without risk
      factors].

PMID- 10919136
TI  - [Spontaneous splenic rupture caused by spleen peliosis in a patient with
      autoimmune thrombocytopenic purpura treated with danazol].

PMID- 10919137
TI  - [Genetics of dystonia].
AB  - To date, at least 12 types of primary dystonia can be distinguished on a genetic
      basis. A 3-bp deletion in the DYT1 gene causes early onset, generalized torsion
      dystonia (TD), and mutations in the GTP cyclohydrolase I and the tyrosine
      hydroxylase genes result in dopa-responsive dystonia (DYT5). A missense change in
      the D2 dopamine receptor in one large family (DYT11) has recently been implicated
      in myoclonus-dystonia. Furthermore, seven other loci for dystonia genes have been
      mapped to chromosomal regions, including a locus for a mixed dystonia phenotype
      (DYT6), one form of focal dystonia (DYT7), three types of paroxysmal dystonia
      (DYT8-10), X-linked dystonia-parkinsonism (DYT3), and rapid-onset dystonia
      parkinsonism (DYT12). No positive linkage results have yet been obtained for
      autosomal recessive TD (DYT2) and several other families of different types of
      dominantly inherited TD (DYT4). In addition, hereditary secondary dystonia may
      occur as part of familial diseases of the basal ganglia, metabolic and storage
      disorders, and various X-linked and other familial neurodegenerative syndromes
      affecting the basal ganglia. It may be anticipated that the traditional clinical
      and etiological classifications of dystonia will increasingly be replaced by a
      genetic one and that the identification of more dystonia genes may lead to a
      better understanding of these largely nondegenerative disorders.

PMID- 10919138
TI  - [Peripheral nerve diseases and myopathies associated with HIV infection].
AB  - Diseases of the peripheral nervous system occur in up to 50% of persons infected
      with human immunodeficiency virus (HIV). In early stages of the infection,
      Guillain-Barre syndrome or a spontaneously remitting mononeuropathy can occur.
      The most frequent occurrence is distal symmetrical polyneuropathy associated with
      HIV, which can only be treated symptomatically. The most important differential
      diagnosis is a drug-induced polyneuropathy under antiretroviral therapy with the
      nucleoside analogues DDI, DDC, or D4T. Chronic inflammatory demyelinating
      polyneuropathy is less common and can be treated with immunoglobulins or
      corticosteroids. Very rare are steroid-responsive neuropathies with necrotizing
      vasculitis or in diffuse infiltrative lymphocytosis syndrome (DILS). In the AIDS
      stage, polyradiculitis can occur due to opportunistic infections--most often with
      cytomegalovirus (CMV) or M. tuberculosis--or polyradiculopathies due to
      lymphomatous meningiosis. Mononeuritis multiplex is rarely seen in disseminated
      CMV infection. Myopathies can occur in all stages of HIV infection; their
      frequency is about 1%. Primary polymyositis associated with HIV, which can be
      treated with corticosteroids or immunoglobulin, must be distinguished from
      myopathy induced by azidothymidine. Other forms of myopathy are very rare.

PMID- 10919139
TI  - [Drug therapy before and after surgery for epilepsy. Critical review and
      recommendations].
AB  - As a result of a critical review of the literature and a survey at German
      epilepsy centers of usual pre- and postoperative drug treatment, the following
      strategy is recommended: 1. Patients under consideration for surgery should be
      referred to specialists. Experience has shown that surgery is reasonable for only
      about a third of all patients with refractory epilepsies. The patient should
      first have been treated for at least 3 years with at least two first-line drugs
      in monotherapy and subsequent combined therapy. This applies only to medial
      temporal lobe epilepsies with very good postoperative prognoses. All other
      surgically removable epilepsy syndromes with less positive prognosis should be
      treated with additional antiepileptic drugs before any surgery. 2. There is no
      exception to the continuation of drug treatment after epilepsy surgery. If the
      patient remains free of seizures for at least 2 years, discontinuing the drug
      treatment can be discussed, just as with patients who are free of seizures due to
      drug treatment alone. In general, the less successful the operative therapy, the
      longer and more intensive the drug treatment.

PMID- 10919140
TI  - [Neuroanatomy of Parkinson disease. Changes in the neuronal cytoskeleton of a few
      disease-susceptible types of neurons lead to progressive destruction of
      circumscribed areas in the limbic and motor systems].
AB  - Morbus Parkinson is a progressive degenerative disease of the human central,
      peripheral, and enteric nervous systems. In the course of the disease, not only
      the substantia nigra, but also extranigral components of the motor system, as
      well as numerous limbic system and autonomic centers undergo serious damage.
      Accordingly, Parkinson's disease is a multisystem disorder. Only specific types
      of projection neurons fall victim to it. The first manifestation of the
      pathological process which causes the disease are abnormalities of the neuronal
      cytoskeleton. Intracytoplasmic inclusions evolving in the form of Lewy bodies in
      perikarya and Lewy neurites in the neuronal processes result in premature cell
      death of the affected neurons. On the basis of this selective neuronal
      vulnerability, a categorization emerges of the pathological changes within the
      nervous system and corresponding functional impairments.

PMID- 10919141
TI  - [Surgical treatment of carpal tunnel syndrome in pregnancy: results from 314
      cases].
AB  - A total of 314 hands of patients suffering from carpal tunnel syndrome (CTS) in
      pregnancy or puerperium were treated by carpal tunnel release. In 53% of these
      cases, other members of the family were also affected, usually the mother. Ninety
      seven patients were operated upon at both hands. One hundred thirty-three
      operations were performed during pregnancy, mostly in the last trimester, and 181
      during puerperium. In four patients, the operation was performed on both hands
      simultaneously. There were also 12 cases of associated De Quervain's
      tenosynovitis and ten trigger fingers. Severe night pain and/or permanent
      hypoesthesia was experienced by 93% of the patients. All patients were operated
      on with local anesthesia and in a bloodless field. The distal motor latency was 7
      +/- 1.5 ms in cases with hypoesthesia and 4.9 +/- 1.75 ms without sensory loss.
      Of the patients, 98% reported good or excellent results of the operation during
      pregnancy via questionnaires. Since symptoms are often very severe in pregnancy
      and puerperium and the operation is well-tolerated by pregnant women and without
      risk to either mother or child, we recommend surgery, especially when sensory
      loss is present and motor latency is more than 5 ms.

PMID- 10919142
TI  - [Tendovaginitis stenosans: a frequent complication of carpal tunnel syndrome].
AB  - Of 1310 patients surgically treated for carpal tunnel syndrome (CTS), 134 (10.2%)
      were observed to have one or more trigger fingers or de Quervain's disease. Of a
      total of 205 fingers, the middle finger was affected 75 times, the ring finger 50
      times, the thumb 47 times, the small finger 17 times, and the index finger 16
      times. Chronic nonspecific synovitis is commonly suspected as the cause of both
      diseases. In all cases of carpal tunnel syndrome, the patient should therefore be
      examined for symptoms of concomitant trigger finger and vice versa. Both can be
      cured surgically under local anesthesia and bloodless field in a single session.

PMID- 10919143
TI  - [Temporal lobe epilepsy: effect of focus side on the autonomic regulation of
      heart rate?].
AB  - Epileptic activity can modulate reactions of the autonomic nervous system.
      Although there is some evidence of a differential left/right hemispheric
      influence on the cardiovascular system, diverse investigations have shown
      controversial results. In our study, complex partial seizures of patients with
      temporal lobe epilepsy were recorded using subdural electrodes, thus providing
      reliable information on the focus side. We analyzed the preictal and ictal heart
      rates of 27 patients, 16 revealing right and 11 revealing left temporal foci.
      During the seizures, both groups showed a significant increase in heart rate.
      Preictal tachycardia was only significant in the right focus group, whereas no
      significant change in heart rates could be detected in the left focus group. Our
      results confirm a right hemispheric lateralization of sympathetic cardiac
      control.

PMID- 10919144
TI  - [Gliomatosis cerebri: two case reports with atypical clinical and neuroradiologic
      findings].
AB  - The diagnosis of the rare disease Gliomatosis cerebri requires the correlation of
      clinical, radiological, and pathological findings. We report on two patients with
      intravitally diagnosed gliomatosis cerebri. Due to the unusually high malignancy
      of the tumor cells, diagnosis was complicated by atypical findings such as
      gadolinium enhancement in MRI and raised intracranial pressure. The clinical
      course, differential diagnosis, and literature are summarized briefly.

PMID- 10919145
TI  - [Anatomic substrate of epigastric aura: case report].
AB  - Epigastric sensations are the most frequent type of aura in medial temporal lobe
      epilepsy. Until now, the site of the symptomatogenic zone of the epigastric aura
      remains controversial. The temporal lobe has been discussed, as well as the
      insular cortex. The case presented here supports the assumption of an insular
      origin of the epigastric aura. A 44-year-old male suffered from typical
      psychomotor seizures preceded by an epigastric aura. Imaging revealed a cavernoma
      located in the right insular region, the ipsilateral temporal lobe being
      otherwise unremarkable. The lesion was surgically removed, leaving the temporal
      lobe untouched. Apart from one clinical episode that was unlike his habitual
      seizures, the patient remained free of seizures (including auras). We conclude
      that the insular cortex was most likely the symptomatogenic zone for this
      patient's epigastric auras. Although it can not be excluded that this patient's
      aura resulted from ictal activation of other brain structures, the successful
      lesionectomy is in favor of our hypothesis.

PMID- 10919146
TI  - [Hashimoto encephalopathy: steroid-sensitive encephalopathy in Hashimoto
      thyroiditis].
AB  - Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive
      encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical
      features are confusion, seizures, alteration in conscious level, stroke-like
      episodes, myoclonus, and tremulousness. High CSF protein levels without
      pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI
      and cerebral angiogram are usually normal. We present two case reports of
      Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded
      well to steroid therapy, and review the literature.

PMID- 10919147
TI  - [Topiramate (Topamax). Pharmacological characteristics and current use in
      epilepsy treatment].
AB  - Topiramate (Topamax) has been registered since July 1998 and has market
      authorization for the Federal Republic of Germany as an additive drug for the
      treatment of patients (age 12 or older) suffering from intractable partial and
      secondarily generalized seizures. The anticonvulsant effect of topiramate is
      based on three mechanisms: (a) modulating the blocking of the Na channels
      activated by voltage, depending on status, (b) potentiation of GABAA-mediated
      inhibiting neurotransmission, and (c) inhibition of excitatory neurotransmission
      by blocking APMA glutamate receptors. Topiramate exhibits a substantial
      anticonvulsive effect on partial seizures both with and without secondary
      generalization. The median reduction in seizure frequency using topiramate as
      adjunct therapy was 44%. In 44% of patients, seizure frequency was reduced by
      more than 50%, and seizure reduction was more than 75% in nearly half of these
      (i.e., in 21% of all patients), while 5% of patients remained completely free of
      seizures. Adverse events most often caused central nervous disturbances. Weight
      loss, the development of renal calculi, and impairment of cognitive functions may
      occur. It is recommended to start therapy with topiramate at a daily dosage of 25
      mg, increasing by 25 mg every week up to 200-400 mg/day but not exceeding 1000
      mg/day.

PMID- 10919148
TI  - [Raeder- and Collet-Siccard-Syndrome. Acute pareses of cranial nerves symptomatic
      of a dissection of internal carotid artery].
AB  - Acute cerebral nerve paresis can be caused in many different ways. One of the
      more rare causes of paresis of one or more neural pathways is dissection of the
      internal carotid artery. Early diagnosis is important, even with atypical
      symptoms, since prompt anticoagulative therapy can hinder stroke from embolism
      due to the dissection. We report on two patients with Raeder's syndrome and
      Collet-Sicard syndrome resulting from dissection of the internal carotid artery.
      Besides the cranial and caudal nerves involved in our study, loss of function has
      also been reported with the sixth to eighth cranial nerves, so that any painful,
      sudden cranial nerve deficiency can indicate possible carotid dissection.

PMID- 10919149
TI  - [Historical contribution on consumption of herbal narcotics].

PMID- 10919150
TI  - [Justinus Kerner. Comments on cover illustration].

PMID- 10919151
TI  - [The indications for autonomic nerve-sparing surgery in rectal cancer patients].
AB  - Although extended lymph node dissection was developed to improve the therapeutic
      result in advanced rectal cancer in the 1970s, postoperative dysfunction remained
      problematic. Informed consent of cancer is generalized at present. The balance
      between complete cure and functional preservation is important. Therefore the
      autonomic nerve-sparing surgical technique for rectal cancer was introduce din
      the 1980s. The success of nerve-sparing surgery depends on a thorough knowledge
      of pelvic anatomy, especially the anatomic relationship between the pelvic plexus
      and internal intestinal vessels. Further investigation is required to clarify the
      indications for autonomic nerve-sparing surgery in rectal cancer patients.

PMID- 10919152
TI  - [Autonomic nerve-sparing surgery combined with preoperative radio-chemotherapy in
      advanced lower rectal cancer patients].
AB  - Since 1985, we have studied autonomic nerve-sparing surgery combined with
      preoperative radiochemotherapy in patients with advanced rectal cancer to
      preserve genitourinary function without compromising radicality. The aim of this
      study was to evaluate postoperative genitourinary function and prognosis. A total
      of 84 patients with advanced rectal cancer underwent curative surgery combined
      with preoperative radio-chemotherapy. Of them, 76 underwent curative nerve
      sparing surgery using radiation (42.6 Gy) and tegafur suppository. Postoperative
      genitourinary function, survival, and pelvic recurrence were investigated in
      these patients. The 5-year and 10-year disease-free survival rate was 80.7%, and
      the pelvic recurrence rate was 7.9% in patients receiving curative nerve-sparing
      surgery combined with radio-chemotherapy. All of these patients could micturate
      spontaneously, but preservation of sexual function was not as successful.
      Although this combined therapy is useful for curability and good postoperative
      quality of life, a new approach is needed to preserve sexual function.

PMID- 10919153
TI  - [Indications for and limitations of low anterior resection].
AB  - The indications for low anterior resection are based mainly on tumor location,
      penetration depth, histology, macroscopic appearance, etc. Patients with tumors
      located 2 cm above the puborectal muscle by digital examination can undergo low
      anterior resection. Distal surgical margins should be at least 1 cm from the
      tumor in cases of differentiated cancer and localized tumors of stage T2 or less
      and more than 2 cm in poorly differentiated cancer and tumors of stage T3 or
      greater with total mesorectal excision (TME). Longer distal surgical margins
      should be provided in patients with unlocalized tumors and extensive node
      metastasis. The final decision on whether low anterior resection is appropriate
      should be made after mesorectal preparation down to the levator muscles with
      adequate surgical margins. Low anterior resection is contraindicated in patients
      with poor anorectal function and high age. A rectal stump 1 to 2 cm from the
      dentate line should be maintained for better postoperative anorectal function if
      radical excision can still be performed.

PMID- 10919154
TI  - [Sphincter-preserving surgery: per anal coloanal anastomosis].
AB  - Since the introduction of the stapling technique, sphincter-preserving surgery
      for treatment of rectosigmoid and upper rectum carcinoma has been widely
      performed in the view of its radicality and postoperative quality of life.
      Sphincter preservation is still controversial in carcinoma of the lower rectum.
      Since we introduced per anal coloanal anastomosis (PAA) in 1980 and per anal
      intersphincteric dissection and coloanal anastomosis (PIDCA) in 1993 for the
      treatment of lower rectal carcinoma, the sphincter has been preserved in 78.7% of
      patients. There was no significant difference in the 5-year survival rate between
      patients in whom the sphincter was preserved and those who underwent
      abdominoperineal resection during the same period. PAA and PIDCA are safe when
      anastomosis must be performed at the dentate line. They are the best sphincter
      preserving techniques for lower rectal carcinoma and do not result in serious
      postoperative dysfunction.

PMID- 10919156
TI  - [Reconstruction of anal function after abdomino-perineal resection].
AB  - After abdomino-perineal resection for rectal cancer, most surgeons believe that
      colostomy is necessary after anal function is abolished and that patients are
      satisfied with this. Recently, reconstruction of anal function has been performed
      using new surgical techniques such as creation of an artificial sphincter,
      dynamic graciloplasty, gluteoplasty with pudendal nerve anastomosis, and smooth
      muscle implanted neoanus. However, most surgeons do not have sufficient knowledge
      of reconstruction of anal function. Since all reconstruction methods are
      associated with low mortality and morbidity rates, and can be converted to
      conventional colostomy when required, surgeons must consider first-line
      reconstruction of anal function after resection of the anal sphincter.

PMID- 10919155
TI  - [Sphincter-preserving surgery for lower rectal cancer aimed at improving
      postoperative bowel function].
AB  - Much attention has been focused on sphincter-preserving surgery for patients with
      lower rectal cancer, leading to renewed interest in the outcome of postoperative
      bowel function. Some patients who undergo sphincter-preserving surgery experience
      bowel dysfunction, such as frequent stools, severe constipation, soiling, and
      incontinence. These symptoms were thought to be correlate with lower resting
      pressure, lower rectal compliance, sensory disturbance of the anal canal, spasm,
      and delayed transit in the colon above the anastomosis. To improve postoperative
      bowel function, reconstruction with the colonic J-pouch has been performed, which
      results in a satisfactory functional outcome. About 80% of patients with a J
      pouch were able to tolerate over 10 minutes after feeling the desire to defecate.
      An anorectal manometric study showed no abnormal spastic movement of the
      neorectum and a transit study showed that the J-pouch group was superior to the
      straight group with respect to the smoothness of movement of radiopaque markers
      from the cecum to anal ring, although a small number of markers were retained in
      the colonic J-pouch. Patients who received a colonic J-pouch had fewer defecation
      problems in daily life. Further study is need to improve postoperative bowel
      movement in patients who undergo sphincter-preserving surgery.

PMID- 10919157
TI  - [Genetic analysis for colorectal cancer: what can we learn from microsatellite
      research?].
AB  - Recent advances in molecular biology have unveiled the mechanisms of
      carcinogenesis, especially colorectal carcinogenesis. A large body of evidence
      supports the idea that accumulated genetic changes due to inherited as well as
      environmental factors underlie colorectal cancer development. Recently, several
      reports have suggested that aberrant methylation of the CpG island may also play
      an important role in colorectal carcinogenesis. This genetic information is not
      yet sufficient but some useful genetic information can be applied clinically.
      This paper presents the results of intensive study of microsatellite instability
      in colorectal cancers and some clinically applicable discoveries. Future problems
      are also discussed.

PMID- 10919158
TI  - Radionuclide esophageal transit test to detect esophageal disorders in patients
      with mitral valve prolapse.
AB  - AIM: The origin of chest discomfort in patients with mitral valve prolapse (MVP)
      is controversial. Our aim was to prospectively determine the incidence of
      esophageal disorders in MVP patients with or without chest pain. METHODS: Twenty
      five MVP patients with chest pain (group A) and 25 MVP patients without chest
      pain (group B) underwent evaluation of esophageal motility. None of the total of
      50 MVP patients had significant coronary artery disease on cardiac
      catheterization. Esophageal motility including esophageal mean transit time
      (MTT), residual fraction (RF), and retrograde index (RI) was analyzed by the
      radionuclide esophageal transit test (RETT). RESULTS: In comparison with 25 age
      and sex-matched healthy volunteers, the results showed that: (1) 19 patients in
      group A (76%) had abnormal RETT findings (48% of cases with prolonged MTT, 44% of
      cases with higher RF, and 60% of cases with higher RI); (2) 3 patients in group B
      (12%) had abnormal RETT findings (8% of cases with prolonged MTT, 4% of cases
      with higher RF, and 8% of cases with higher RI). In addition, mean values of MTT,
      RF, and RI in group A patients were significantly higher than in group B patients
      and healthy volunteers. CONCLUSION: We found that the chest pain in some MVP
      patients may be related to abnormal esophageal motility, based on the evidence
      from a simple and noninvasive RETT.

PMID- 10919159
TI  - [Detection of melanoma metastases with Tc-99m-tetrofosmin].
AB  - AIM: The aim of this study was to evaluate Tc-99m-tetrofosmin whole-body imaging
      in the detection of metastases in patients with malignant melanoma. METHODS: In
      30 patients with suspected melanoma metastases we performed whole body imaging.
      After administration of about 600 MBq Tc-99m-tetrofosmin dynamic images up to 10
      min were performed in 7 patients (1 image per 10 sec) to evaluate the optimal
      tracer uptake in the metastases. In all patients whole-body images were performed
      5-10 min p.i. using an acquisition time of 5 min per image. The final diagnosis
      was confirmed by surgical histology in 30 lesions, by computertomography and
      clinical course in the remaining lesions. RESULTS: Out of 64 melanoma metastases
      49 were detected using Tc-99m-tetrofosmin scintigraphy (49 rp., 15 fn.). The
      overall sensitivity for the detection of malignant lesions was 77%. Referring
      only to the lymph node metastases, the sensitivity was 87% (26 rp.; 4 fn.). The
      maximal tracer uptake was reached 1 min after injection, with a slow decrease in
      the following 10 minutes. The size of the lesions ranged between 0.5 and 7.0 cm
      and the T/B ratios between 1.3 and 3.0 (mean 1.88). CONCLUSIONS: Tc-99m
      tetrofosmin whole body imaging is a simple and side-effectless method for the
      detection of melanoma metastases especially of lymph node metastases. The results
      are comparable to Tc-99m-sestamibi and Tl-201 scintigraphy.

PMID- 10919160
TI  - [Sonographic determination of thyroid volume--comparison with surgical data].
AB  - AIM: Objective of this prospective study was to find out, if especially the
      volume of large nodular goitres can be determined accurately by using
      ultrasonography and the ellipsoid model. METHODS: 100 patients with different
      thyroid disorders, who all underwent a thyroid resection, were examined by a
      single experienced investigator. The preoperative thyroid volume was determined
      by ultrasonography and correlated to the sum of surgically removed and
      postoperative thyroid volume determined by ultrasound. RESULTS: Patients included
      had thyroid volumes between 12 and 450 ml (mean value 89 ml). Within the whole
      study group, coefficients of correlation and variation were r = 0.90 and CV =
      0.29, respectively. The mean difference between the thyroid volume determined
      preoperatively by ultrasonography and the sum of surgically removed and
      postoperative thyroid volume was 3 +/- 27 ml or 13 +/- 38%. Excluding patients
      with retrosternal goitres or cysts with a diameter > 2 cm, the correlation
      coefficient increased to r = 0.95 (CV = 0.21) and mean differences decreased to 2
      +/- 20 ml and 9 +/- 30%. Further subdivision according to thyroid volume (< or =
      50 ml, < or = 100 ml, > 100 ml) revealed no significant influence of thyroid
      volume on the accuracy of ultrasound volume determination. Subdividing the study
      collective according thyroid disorders, relevant deviations of preoperative
      sonographic thyroid volume from the sum of surgically removed and postoperative
      thyroid volume were observed in case of retrosternal goitre (19 +/- 62%), cystic
      degeneration (41 +/- 52%) and Graves' disease (23 +/- 29%). CONCLUSION: These
      results show, that even large suprasternal goitres > 100 ml can be sufficiently
      determined by ultrasound by an experienced examiner.

PMID- 10919161
TI  - [Effect of iodine application during radioiodine therapy in patients with
      impending therapy failure].
AB  - AIM: We investigated whether additional application of "cold" iodine after
      therapy with radioiodine could result in a prolongation of the effective half
      life of iodine-131 and would thus lead to an increase of the effective thyroid
      radiation dose. METHODS: Time-activity-curves after therapy with radioiodine were
      analysed in 25 patients (16 women, 9 men). Nine patients suffered from
      autonomously functioning thyroid nodules, 5 from autonomous multinodular goiter
      and 11 from Graves' disease. These patients had an effective half life shorter
      than 4 days resulting in an undertreatment of > 20% with respect to the desired
      effective thyroid radiation dose. 2-4 days after therapy with radioiodine all
      patients received "cold" iodine for three days in a dose of 3 x 200 micrograms
      per day. RESULTS: In 14 of the 25 patients an increase of the effective half life
      was observed. Patients with an autonomously functioning thyroid nodule showed a
      mean increase of the effective thyroid radiation dose of 40 +/- 44 Gy, patients
      with toxic multinodular goiter of 29 +/- 30 Gy and patients with Graves' disease
      of 37 +/- 37 Gy. CONCLUSION: Additional application of "cold" iodine after
      therapy with radioiodine can prolong the effective half life in selected
      patients. We suspect a correlation with the thyroid iodine pool. This will be the
      basis for further investigations hopefully resulting in a better patient
      preselection to determine who might respond to this therapy.

PMID- 10919162
TI  - [Measurement of thyrotropin receptor antibodies (TRAK) with a second generation
      assay in patients with Graves' disease].
AB  - AIM: The detection of TSH-receptor-antibodies (TRAb) in patients (pts) with
      Graves' disease (GD) is routinely used in nuclear medicine laboratories. It is
      performed by commercial, porcine radioreceptorassays (RRA) measuring TSH binding
      inhibitory activity. A second generation assay using the human, recombinant TSH
      receptor was developed during the last years. The manufacturer composed this new
      assay as a coated tube RRA (CT RRA) and claimed a higher sensitivity for GD.
      METHODS: TRAb was measured in 207 pts with various thyroid disorders and 205
      healthy controls using the new coated tube RRA (Fa. B.R.A.H.M.S. Diagnostica
      GmbH, Berlin, Germany) as well as a conventional RRA (Fa. Medipan Diagnostica
      GmbH, Selchow, Germany): 60 pts suffering from GD showing a relapse after
      antithyroid drug treatment and before radioiodine therapy, 109 pts with
      disseminated autonomia (DA) and 38 pts suffering from Hashimoto's thyroiditis. A
      ROC-analysis was performed to find the optimal decision threshold level for
      positivity. RESULTS: We found 42/60 TRAb-positive pts with GD in the established
      RRA (threshold 6 U/L) and 52/60 in the CT RRA, respectively. The sensitivity
      increased from 70% (RRA) to 86.7% (CT RRA). The CT RRA found 2 false positives
      (one Hashimoto's and one healthy control) and the RRA detected 3 Hashimoto's and
      2 healthy controls as false positive. CONCLUSION: The increased sensitivity of CT
      RRA for GD provides an advantage compared to conventional RRA, especially in GD
      patients relapsing after antithyroid drug treatment. Functional sensitivity and
      Interassay-variation of CT RRA are very precisely compared to conventional RRA.
      Handling of the new assay is also improved.

PMID- 10919163
TI  - Positive bone scan in intraosseous lipoma of the tibia: role and review of
      diagnostic imaging methods.

PMID- 10919164
TI  - Stress fracture and coexistent periosteal reaction ("shin splints") in a young
      athlete revealed by bone scintigraphy.

PMID- 10919165
TI  - [Positive presentation of a localized neuroblastoma in skeletal scintigraphy].

PMID- 10919166
TI  - [Sentinel lymphadenectomy in papillary thyroid carcinoma by means of preoperative
      lymph node scintigraphy and intraoperative gamma probe measurement].

PMID- 10919167
TI  - [Somatostatin receptor scintigraphy (SRS) in a neuroendocrine pancreatic tumor:
      why SPECT?].

PMID- 10919168
TI  - Why do coronary patients gain a clinical benefit from polyunsaturated fatty
      acids?

PMID- 10919169
TI  - Alpha-linolenic acid and heart rate variability.
AB  - BACKGROUND AND AIM: The marine long-chained n-3 polyunsaturated fatty acids seem
      to have antiarrhythmic effects in humans. Similar effect has also been postulated
      for alpha-linolenic acid, a plant-derived polyunsaturated fatty acid--from the n
      3 family. The purpose of the study was to examine the relation between the
      content of alpha-linolenic acid in cell membranes and the risk of malignant
      arrhythmias as assessed by determination of heart rate variability (HRV). METHODS
      AND RESULTS: Patients at high risk of sudden cardiac death (52 with a previous
      myocardial infarction and 29 with chronic renal failure on dialysis) were
      enrolled as well as 64 healthy volunteers. The cell membrane content of alpha
      linolenic acid was analyzed by gas chromatography and related to 24-hour HRV,
      which was measured in all subjects. No correlations were found between levels of
      alpha-linolenic acid and 24-hour HRV. CONCLUSION: The present study was unable to
      demonstrate a positive correlation between cell membrane levels of alpha
      linolenic acid and HRV. Our results suggest that alpha-linolenic acid per se is
      devoid of an antiarrhythmic effect, though this effect could arise from its
      conversion to the longer chained n-3 PUFA, usually derived from fish.

PMID- 10919170
TI  - Beneficial effects of a moderate consumption of red wine on cellular cholesterol
      efflux in young men.
AB  - BACKGROUND AND AIM: Protection against coronary artery disease (CAD) by moderate
      alcohol consumption is thought to be partly mediated through an increase in high
      density lipoprotein (HDL) levels. The protective effect of HDL can be related to
      its role in reverse cholesterol transport. Some studies have shown that wine
      intake is associated with a lower CAD risk compared to other alcoholic beverages.
      METHODS AND RESULTS: In order to separate the possible beneficial effects of the
      alcoholic and the non-alcoholic components of red wine, three beverages were
      compared in a group of 56 healthy young men: red wine (W) (30 g alcohol/day), a
      solution with the same degree of alcohol (A) and alcohol-free red wine (AFW).
      Beverages were consumed in random order over a period of 14 days. W significantly
      increased serum HDL-C, Apo A-I, HDL3-C, LpA-I and LpA-I:A-II particles. With A,
      only ApoA-I, HDL3-C, LpA-I:A-II were increased, though triglycerides were also
      increased. AFW had no effect apart from decreasing HDL-C. Plasma CETP was never
      altered. Serum-promoted cellular cholesterol efflux was measured on 3H labelled
      Fu5AH cells. Fractional cholesterol efflux was increased only after W intake, by
      7%. Efflux variations correlated positively with HDL-C, HDL3-C and HDL
      phospholipid variations. CONCLUSIONS: A modest, specific beneficial effect of
      moderate red wine consumption was demonstrated in comparison to an alcoholic
      solution. This was due to its effects on lipoproteins and its stimulation of
      serum ability to induce efflux of cellular cholesterol.

PMID- 10919171
TI  - Application of simple lipid treatment goals in patients with atherosclerotic
      disease.
AB  - BACKGROUND AND AIM: In this multicentre observational study the "5-4-3-2-1"
      guideline (total cholesterol < 5.0 mmol/L, the ratio of total to high-density
      lipoprotein cholesterol < 4, low-density lipoprotein cholesterol < 3.0 mmol/L,
      triglycerides < 2.0 mmol/L and high-density lipoprotein cholesterol > 1.0 mmol/L)
      was compared with the new European recommendations (total cholesterol < 5.0
      mmol/L and low-density lipoprotein cholesterol < 3.0 mmol/L) ("5-3") and a
      treatment criterion of low-density lipoprotein cholesterol < 3.0 mmol/L and
      triglycerides < 1.5 mmol/L ("3-1.5"), as patients with triglycerides > 1.5 mmol/L
      may have an increased risk of premature cardiovascular disease. METHODS AND
      RESULTS: In 1997/98, 2134 patients in general practice with established
      atherosclerotic disease on a lipid-lowering therapy were monitored. The "5-4-3-2
      1" guideline was met in 19.2% and the "5-3" guideline in 36.2% and 22.5%
      fulfilled the "3-1.5" criterion. Our data showed a good conformity between the "5
      4-3-2-1" guideline and the "3-1.5" criterion. Of the patients who achieved the "5
      3" guideline approximately 50% still had unfavourable values of HDL-cholesterol
      and TG, while only 15% of those who fulfilled the "3-1.5" criterion had HDL
      cholesterol < or = 1.0 mmol/L. CONCLUSIONS: A treatment goal of LDL-cholesterol <
      3.0 mmol/L and fasting TG < 1.5 mmol/L markedly raised the proportion of patients
      with desirable levels of HDL-cholesterol and the ratio of total cholesterol to
      HDL-cholesterol and should be recommended in secondary prevention, especially in
      diabetic patients.

PMID- 10919172
TI  - The patient with CHD: how should we translate international guidelines into
      clinical practice?

PMID- 10919174
TI  - Increasing evidence for the role of salt and salt-sensitivity in hypertension.
AB  - The paper focuses on some aspects of the complex relationship between dietary
      salt intake and blood pressure. The first part is a short review of the evidence
      available from epidemiological and clinical studies, indicating that a moderate
      reduction in dietary salt intake represents an effective non-pharmacological
      measure for the treatment of hypertension and for the prevention of hypertension
      related cardiovascular complications, namely stroke and ischemic heart disease.
      The second part deals with the role of inherited and acquired factors in the
      phenotypic expression of the salt-sensitivity of blood pressure. In particular,
      the influence of sympathetic nervous system hyperactivity, of insulin resistance
      and of alterations of endothelial function in the pathogenesis of salt-related
      forms of hypertension are discussed.

PMID- 10919173
TI  - Why and how to measure urinary sex steroid metabolites in epidemiological studies
      in women.
AB  - BACKGROUND AND AIM: Although numerous investigations have evaluated the
      association between urinary hormone levels and chronic diseases such as breast
      cancer and coronary heart disease, there are few data about the reliability of
      urinary measurements, particularly among premenopausal women. METHODS AND
      RESULTS: Over a six-month period, levels of estrone-3-glucuronide and pregnandiol
      3-glucuronide were measured in both morning spot and overnight urine samples from
      seven healthy premenopausal women (ages 33-46). During this period, each subject
      provided one morning spot urine sample and one overnight urine sample per
      menstrual cycle on the same day of her menstrual cycle. All these samples were
      taken out of the freezer simultaneously and sent in the same parcel on dry ice to
      the laboratory for hormone determinations. All samples from each person were
      assayed simultaneously in the same run and by the same laboratory technician in a
      blind fashion. The intraclass correlation coefficients (ICC) for estrone-3
      glucuronide and pregnandiol-3-glucuronide for the morning spot and overnight
      urine samples were 0.78 and 0.46 and 0.75 and 0.64 respectively. CONCLUSIONS:
      These data suggest that morning spot urine determinations are reliable and
      constitute an efficient alternative to the more complex overnight urine
      collection for epidemiological evaluation of urinary hormonal profiles.

PMID- 10919175
TI  - Transforming growth factor beta and coronary artery disease.

PMID- 10919176
TI  - [Guidelines for employment policies in Europe and national action plans:
      opportunities for people with disabilities].
AB  - The scourge of unemployment has been roundly identified throughout Europe as the
      most pressing social and economic problem on the current political agenda. At
      Luxembourg in November 1997, the European Jobs Summit brought Europe's leaders
      together in an historic occasion that mapped out employment guidelines for
      Europe. The Luxembourg Jobs Summit agreed a set of guidelines for the Member
      States employment policy under four pillars, employability, entrepreneurship,
      adaptability, and equal opportunities. One guideline referred to promoting
      integration of people with disabilities into working life. The Member States
      subsequently agreed to incorporate the Guidelines into national employment action
      plans. The question of this paper is, to what extent do employment guidelines and
      National Action Plans improve the opportunities of disabled persons? This paper
      seeks to establish a set of fundamental issues concerning employment and
      disability. Included in this analysis are recommendations in order to achieve a
      better presence of disabled people in National Action Plans in future.

PMID- 10919177
TI  - [Effectiveness and usefulness of neuropsychological rehabilitation methods].
AB  - Every year, more than half a million people in Germany experience a stroke or a
      traumatic brain injury. A high percentage of them leave the hospital with
      neuropsychological deficiencies of attention, memory, speech or perception
      preventing them from returning to work. The German rehabilitation system is
      primarily funded by the statutory pension insurance system and is hospital-based,
      but only very few brain-damaged patients have the opportunity to be treated
      there. Hospital rehabilitation programmes often integrate neuropsychological
      trainings whereas neuropsychologically based outpatient programmes do not exist.
      Therefore two questions are crucial. First, are those separate neuropsychological
      trainings effective? Second, are positive effects generalized? Studies concerning
      these questions are reviewed. Not many of them, however, meet the usual
      requirements for valid intervention research, and their findings are equivocal.
      Nevertheless, they suggest that neuropsychological rehabilitation should be
      undertaken more frequently, which would offer a framework for future efficacy
      research.

PMID- 10919178
TI  - [Orthopedic traumatologic rehabilitation--a superfluous anachronism?].
AB  - In orthopaedic-traumatologic rehabilitation, muscular atrophies, joint
      contractures, bone loss and other restrictions of the locomotor system can be
      prevented or at least diminished. After an operation in particular, decreases in
      physical capacity of the locomotor and cardiopulmonary systems are common, which
      can be countered by special training therapies. Therefore, an effective
      rehabilitation programme is necessary including specific therapy forms and
      training concepts based on scientific findings in sports medicine, performance
      physiology and training sciences, in orthopaedics and traumatology as well as
      further medical disciplines. Determination of the load on the locomotor system
      and examination of cardiopulmonary capacity are important basic elements of
      rehabilitation training. Rehabilitation should include intense muscular and
      regular endurance training where loads must be tuned to the patient's individual
      capacity. Overuse syndromes can be avoided by planning regeneration breaks
      between training units and by continuously controlling the individual parameters
      of the patient. The costs of intense rehabilitation may at first seem high;
      however, one year after an operation the financial expenditures in those patients
      who did not receive intense rehabilitation exceeded all costs incurred for an
      operation and additional rehabilitation.

PMID- 10919179
TI  - [Position with respect to the basic points of SGB IX OF 28.10.1999 taking into
      consideration the "rough draft 2" of a SGB IX of 27.1.2000. German Society for
      Rehabilitation of the Disabled e.v].

PMID- 10919180
TI  - [Report on the Annual Membership Meeting (GeneraL Assembly) of REHABILITATION
      INTERNATIONAL (RI)September 8-10th, 1999 in London].

PMID- 10919181
TI  - [Value of the ERGOS work simulator as a component of functional capacity
      assessment in disability evaluation].
AB  - The use of assessment instruments in evaluating functional capacity is an
      important element in the process of social-medical judgement of whether a person
      will likely be able to reintegrate into working life. Standardized work processes
      are used in simulating occupational reality over several hours, with all the
      requirements involved, and the performance found is contrasted with the
      requirements to be expected at a workplace. Time-tested in the U.S. for more than
      20 years and applied throughout Germany for some two years now, the ERGOS work
      simulation system is presented in the article, using a case example for more
      detailed description. Using five different work stations, performance data are
      collected for job tasks such as carrying, working in kneeling position or
      overhead, and subjected to computer-based comparison with the job requirements
      information contained in relevant databases. This enables computerized
      identification of excessive demands, and hence may point to a need for further
      rehabilitative action. An important feature is objective assessment, as
      subjective information on the basis of observation or reports of painfulness are
      raised separately, hence do not influence the findings of the work simulation
      performed.

PMID- 10919182
TI  - [The pattern of DNA fragmentation in pediatric neuromuscular disorders].
AB  - INTRODUCTION: An apoptotic mode of cell death has been identified in the
      developing skeletal muscle of invertebrates. It has been also involved in the
      pathogenesis of muscle degeneration in the dystrophin-deficient mdx mouse. This
      has raised an interest on the possible role of apoptosis in human neuromuscular
      disorders, but the existing studies have offered conflicting results. OBJECTIVE:
      To analyze the presence of apoptosis in several pediatric neuromuscular
      disorders. PATIENTS AND METHODS: Identification of cells with apoptotic
      morphology, detection of DNA fragmentation in situ by means of the TUNEL assay
      and study of the pattern of DNA fragmentation by agarose gel electrophoresis and
      Southern blot hybridization in muscle biopsies of 29 patients and three normal
      controls. RESULTS: No morphological features of apoptosis were found in any of
      the samples examined. The TUNEL method did not label the myonuclei from any of
      the biopsies, though some mastocytes stained positively. Agarose gel
      electrophoresis of extracted DNA and Southern blot hybridization with a genomic
      DNA probe did not show oligonucleosomal fragmentation. However, smearing of DNA
      was observed in samples from three patients affected with Duchenne's muscular
      dystrophy, one with Becker's muscular dystrophy and one with infantile spinal
      muscular atrophy. CONCLUSIONS: The present results do not favor the hypothesis of
      persistent apoptosis in some of the pediatric neuromuscular disorders, although
      they do not exclude that some sort of programmed cell death occurs either
      excessively or anachronically at other stages of the pathogenesis of these
      diseases.

PMID- 10919183
TI  - [The classical clinical and neuroimaging features of meningiomas are mimicked by
      other intracranial, supratentorial expansive lesions].
AB  - OBJECTIVE: To analyze the surgical neurology cases in which both the clinical and
      neuroimaging features suggested supratentorial meningioma, and resulted in
      different entities from the neuropathological point of view. PATIENTS AND
      METHODS: The clinical histories of patients harboring intracranial,
      supratentorial mass lesions diagnosed as meningioma operated in different
      hospitals of Maracaibo, Venezuela, during the period 1993-1997 were reviewed.
      RESULTS: Our analysis revealed 15 cases with different neuropathological
      diagnosis. They were distributed as follows: three cases of hemangiopericytoma,
      two cases each of anaplastic ependymoma, metastatic carcinoma, and solitary
      intracranial plasmacytoma, and one case each of plasma cell granuloma,
      pleomorphic xanthoastrocytoma, chondroma, actinomycetoma, meningeal fibroma and
      chronic inflammation not otherwise specified. CONCLUSION: A heterogeneous group
      of intracranial, supratentorial expansive mass lesions can masquerade as
      meningiomas both from the clinical and neuroimaging points of view.

PMID- 10919185
TI  - [Diffusion-weighted magnetic resonance in the diagnosis of acute subcortical
      infarcts].
AB  - INTRODUCTION: The diagnostic efficacy of radiological studies in acute
      subcortical infarcts is limited by the low sensitivity of conventional
      computerized tomography (CT) and magnetic resonance (MR) in detecting small-sized
      infarcts, and the difficulty in differentiating acute from chronic lesions.
      Diffusion-weighted MR (DMR) has shown great sensitivity and specificity in the
      detection of small vessel ischemic lesions during the acute phase. OBJECTIVE: To
      determine the diagnostic value of DMR in the study of patients with subcortical
      infarcts during the acute phase. PATIENTS AND METHODS: We made a prospective
      analysis of 100 consecutive patients with a clinical diagnosis of subcortical
      infarct. In all cases MR examination was done within the first 10 days (average
      3.9 days) following onset, using conventional and diffusion-weighted sequences.
      RESULTS: In all cases the DMR showed the presence of ischemic lesions which
      explained, at least partly, the clinical features of the stroke. In 42 patients
      (42%) the DMR gave relevant information for diagnosis, as compared with the
      conventional MR studies, by confirming the presence of an ischemic lesion
      responsible for the clinical picture. The percentage rose to 50% when the
      examination was done within the first two days. CONCLUSIONS: DMR gives useful
      information in a high percentage of patients with acute subcortical infarcts.
      This is due to its great sensitivity in the detection of acute lesions of small
      size, and capacity to distinguish acute from chronic lesions.

PMID- 10919184
TI  - [Acute pharmacological test with clonidine for the tremor in patients with
      Parkinson disease].
AB  - INTRODUCTION: Idiopathic Parkinson's disease has a prevalence of 1/1,000 and in
      70-75% of these patients tremor is the commonest symptom. Of all the typical
      symptoms of this disease, the tremor is the most difficult to control. It is
      therefore necessary to seek drugs to solve this serious problem. OBJECTIVE: To
      evaluate the usefulness of clonidine in the acute treatment of resting and
      postural tremor in patients with idiopathic Parkinson's disease. PATIENTS AND
      METHODS: Acute pharmacological test (administration of 0.3 mg of clonidine
      chlorhydrate intramuscularly). The evaluation was done using a clinical protocol
      before administration and 30, 60, 120 and 240 minutes afterwards. Statistical
      comparison was done by variance analysis, taking a value of p < 0.0025 as
      significant. We included 28 patients (15 men and 13 women) of an average age of
      66.9 years, and average duration of the disease of 5.53 years. Diagnosis followed
      the strict criteria of UKDDDSBB. RESULTS: There was no difference in the
      evaluations before and after the first dose of L-dopa. For both types of tremor,
      from 60 minutes onwards there were significant differences, with the maximum 120
      minutes after administration (p < 0.0001). CONCLUSIONS: Clonidine is useful in
      the acute treatment of postural and intention tremor in patients with idiopathic
      Parkinson's disease. Its action is that of reducing the liberation of
      noradrenaline, synergically with the exciting dopaminergic system. It also seems
      to reduce the activity of spontaneous discharge at both thalamic and cortical
      levels.

PMID- 10919186
TI  - [Attention deficit hyperactivity disorder. Cerebral asymmetry observed on
      magnetic resonance].
AB  - INTRODUCTION: Anatomical and functional neuroimaging data from subjects with
      Attention Deficit Hyperactivity Disorder (ADHD) have consistently implicated a
      reversal of cerebral asymmetry and suggested a fronto-striatal dysfunction in
      this disorder. OBJECTIVE: The aim of this study is to investigate the brain
      asymmetries in a homogeneous and non-medicated sample of adolescents with ADHD
      who had been previously studied in our laboratory. PATIENTS AND METHODS: T1
      weighted magnetic resonance images were obtained for 11 adolescents with ADHD and
      19 control subjects. Frontal and posterior brain regions, caudate nucleus, and
      ventricular system were quantitatively measured. RESULTS: A reversed pattern of
      asymmetry for the caudate nucleus (right > left) was found in ADHD when compared
      to the control group. We also found a reversed pattern of asymmetry for the
      frontal lobe (right < left) and a smaller right frontal volume (prefrontal
      specifically) in the ADHD subjects most severely impaired. Right caudate and
      frontal measures were inversely correlated. CONCLUSIONS: ADHD is associated with
      fronto-striatal abnormalities, which may be explicable via extant
      neurodevelopmental theories. Enlargement of the right caudate nucleus may suggest
      the failure of a process of synaptic 'pruning' by which attentional functions
      could be improperly transferred from the basal ganglia to frontal regions during
      development.

PMID- 10919187
TI  - [West syndrome: a chronobiological approach].
AB  - INTRODUCTION AND OBJECTIVES: Chronobiology is the discipline involving the study
      of the time structure of living creatures. Since it has been shown that there is
      non-chaotic recurrence, at precise intervals of time, of different functions from
      unicellular level to complex human systems, rhythmometric evaluation of key
      activities such as the activity-rest and sleeping-waking cycles appear to be
      useful non-invasive instruments for study of time structure in patients with
      episodic illness of the central nervous system (CNS) such as the epilepsies, in
      this case a serious variety of this disorder in childhood: West's syndrome.
      PATIENTS AND METHODS: We studied the activity-rest and sleep-waking cycles of two
      patients with West's syndrome and also their parents, using actometres (ZAK, made
      in Germany). At the same time the parents kept diaries (which they had previously
      been taught to do) at intervals of 20 minutes. They recorded the time of meals,
      administration of medicines, occurrence of seizures and data regarding the sleep
      of the patients. On subsequent analysis actograms were obtained. These are
      quantitative recordings of continuous motor activity. RESULTS: A rhythm of a type
      lasting more than 24 hours was observed during the activity-rest and sleep-waking
      cycles in both patients, with predominance of seizures during the early hours of
      the day. There was also a high degree of synchronization in the mother-child
      interactions. CONCLUSION: The presence of a rhythm of more than 24 hours in
      activity-rest and sleeping-waking shows the marked immaturity of the CNS in these
      patients, directly related to the severity of this type of epilepsy.

PMID- 10919188
TI  - [The importance of TTR met 30 in the diagnosis of familial amyloidotic
      polyneuropathy in the absence of a positive family history].
AB  - INTRODUCTION: Familial amyloidotic polyneuropathy type I is an hereditary
      autosomal dominant disease, characterized by having a mutant transthyretin (TTR
      met 30). For this reason there is a deposition of amyloid in several organs with
      their subsequent malfunction. The most characteristic clinical presentation is
      peripheral, sensomotor and autonomic neuropathy. The dysautonomic component is
      seen early and often dominates the clinical picture. Subsequently, there is
      cardiac, ocular or renal involvement and death generally occurs 10 to 15 years
      after onset of the disorder. In Portugal one thought the gene was fully penetrant
      and, thus, a positive family history was an important criterion for the
      diagnosis. However an increasing number of patients without a positive family
      history have been identified. CLINICAL CASES: We present the cases of three men
      and a woman, aged between 36 and 48 years, with clinical sensomotor and autonomic
      polyneuropathy. There was no known family history of the condition in any case.
      Nerve biopsy in three of the patients, and biopsy of abdominal fat in the other
      patient, showed amyloid to be present. Similarly, TTR met 30 analysis was
      positive in all cases, and allowed the diagnosis to be established. CONCLUSION:
      It is essential to do TTR met 30 analysis in all patients with peripheral
      polyneuropathy in whom there is obviously a dysautonomic component and no known
      family history.

PMID- 10919189
TI  - [McArdle's disease in a 14-year-old girl with fatigability and raised muscle
      enzymes].
AB  - INTRODUCTION: McArdle's disease is a disorder of muscle energy metabolism caused
      by a deficit of muscle phosphorylase. The typical form presents with fatigability
      muscle cramps and pains triggered by physical exercise. Some cases have few
      symptoms. We report the case of a 14 year old girl diagnosed on finding a
      significantly raised CPK, studied following her complaint of fatigability.
      CLINICAL CASE: A 14 year old girl presented with a CPK of 1,243 UI/l (normal 10
      32) which had been requested in view of her fatigability. She had never had
      cramps, muscle pains or dark urine. Neurological examination was normal. The
      levels of CPK after intense exercise on the previous days were 7,459 UI/l, and
      after rest for one week were 283 UI/l (normal 25-230). The ischemic exercise test
      showed that she was unable to finish the test, with flat lactate and pyruvate
      curves and markedly raised ammonia (basal 89 and maximum 571 micrograms/dl). On
      muscle biopsy, the morphology of the striated muscle was seen to be normal and
      staining for myophosphorylase was negative. CONCLUSIONS: The fluctuations of
      muscle enzyme levels in relation to exercise orientate the diagnosis towards a
      disorder of muscle energy metabolism. To detect this, the investigation should be
      carried out following severe exercise for several days and then compared with a
      further test after some days of rest. The ischemic exercise test permits
      identification of defects of glycogenolysis, orientating the choice of suitable
      histochemical, enzymatic or molecular biological tests.

PMID- 10919190
TI  - [Cryptococcosis of the central nervous system. A report of five cases].
AB  - INTRODUCTION: Since the 1980s, in relation to the spread of AIDS, there has been
      an enormous increase in cryptococcosis, a mycotic disorder which usually affects
      the central nervous system (CNS). This disease is caused by Cryptococcus
      neoformans, a microorganism acquired by inhalation of bird excrement. This germ
      produces a capsule which protects it from phagocytosis, can synthesize melanin
      which acts as an antioxidant of the cytotoxic lymphocytes and can reproduce at
      body temperature. Clinically it may show as chronic or subacute meningitis and/or
      encephalitis, as endocranial hypertension or as an intracranial space occupying
      lesion (crytococcoma). To establish the diagnosis, Chinese ink, culture and the
      latex agglutination test are useful. Treatment is with amphotericin B associated
      or not with fluocytokine and fluconazole, the protocol used depending on the
      clinical form. OBJECTIVE: To review the most up-to-date literature on
      cryptococcosis of the CNS to study the condition in relation to five cases.
      CLINICAL CASES: We report five patients with cryptococcosis of the CNS diagnosed
      and treated in the Instituto Nacional de Neurologia y Neurocirugia de la Habana,
      Cuba, showing an increase in the frequency of the occurrence of cases not related
      to HIV infection, great variety of clinico-humoral presentation and the
      characteristics of the treatment given. CONCLUSION: Cryptococcosis can be cured
      completely when the condition is diagnosed early; without treatment it is
      invariably fatal.

PMID- 10919191
TI  - [Diabetes insipidus as a manifestation of cerebral toxoplasmosis in an AIDS
      patient].
AB  - INTRODUCTION: In AIDS patients the endocrine system is often affected. Diabetes
      insipidus (DI) is uncommon and has been related to drugs and infections of the
      central nervous system (toxoplasmosis, cryptococcic meningitis, cytomegalovirus
      encephalitis). In these patients at the time of diagnosis, imaging investigations
      are often normal. CLINICAL CASE: We report the case of a 40 year old man with
      infection category HIV C3 (CD4 < 50 mm3 and viral load 301,258 copies/ml), not on
      antiretroviral treatment at the time of hospital admission. He had polyuria (8-10
      litres/day) and polydipsia for the previous 15 days, with no other symptoms. The
      dehydration test showed central DI (raised osmolarity following subcutaneous
      desmopresin). On MNR there were bilateral periventricular nodular images, also
      present in both caudate nuclei, with ring increased uptake following
      administration of paramagnetic contrast. On the clinical suspicion of cerebral
      toxoplasmosis empirical treatment was started with sulphadiazine and
      pyrimethamine together with nasal DDAVP, obtaining a good clinical response.
      CONCLUSIONS: In patients with HIV infection, DI, although uncommon, may be the
      first sign of cerebral toxoplasmosis. Imaging studies may be pathological and
      assist diagnosis.

PMID- 10919192
TI  - [The phenomenon of diaschisis in cerebral vascular disease].
AB  - INTRODUCTION AND OBJECTIVE: Diaschisis is a physiological phenomenon based on
      reversible depression of functions anatomically or functionally connected to the
      damaged area. Its study has become more interesting over the past twenty years,
      due to the advances made in functional neuroimaging techniques and their possible
      participation in the recovery of function. Our objective is to review the main
      types of diaschisis and their clinical contribution. DEVELOPMENT: At present it
      has mainly been described in cerebrovascular pathology, and been classified
      according to the connecting fibres involved. When the connecting fibres are intra
      hemispheric, the phenomenon of ipsilateral thalamic or subcortical-cortical
      diaschisis may be seen; when they are interhemispheric, there is transcallosal
      diaschisis, and if they are cerebellar, the diaschisis is of the contralateral
      cerebellum or crossed cerebellar diaschisis. Ipsilateral thalamic and crossed
      cerebellar diaschisis are phenomena which are frequently observed, but have no
      clinical significance. Regression of the subcortical-cortical and transcallosal
      diaschisis might explain the neuropsychological and functional neuroimaging
      changes observed over the first few months after the vascular incident.
      CONCLUSION: Study of the different types of diaschisis should be considered in
      patients with cerebrovascular disease since it is potentially reversible, and to
      differentiate it from focalization due to the lesion.

PMID- 10919193
TI  - [Neural bases of perception and recognition of faces].
AB  - OBJECTIVE: To analyze the neural bases of perception and the recognition of
      faces. First of all we consider the concept of functional hemisphere
      specialization; then we look at the results obtained with regard to the
      neuroanatomy of processing faces and finally refer to the disorders of
      recognition of faces in humans. For this we review the clinical evidence obtained
      from the neuropsychological studies of prosopagnostic patients and the data
      derived from psychophysiological experiments done using intracranial recordings
      of nonhuman primates. DEVELOPMENT: The agreement between the results analysed
      allows us conclude that in both cerebral hemispheres there are neural mechanisms
      specialized in the perception and recognition of faces, and in particular the
      ventral and posterior regions of the occipito-temporal cortex play a decisive
      part in these processes. Similarly experimental findings in nonhuman primates
      permits explanation of the neural nature of certain neuropsychological disorders
      seen in man, such as the case of the dissociation between disorders of the
      recognition of facial identity and disorders of recognition of emotional
      expression, and also dissociation between the difficulty in recognizing familiar
      faces and difficulty in recognizing non-familiar faces. CONCLUSION: The use of
      modern neuroimaging techniques and electrophysiological studies using evoked
      potentials are necessary for greater understanding of these and other disorders
      related to processing facial information.

PMID- 10919194
TI  - [The role of cortical oscillatory activity in information processing mechanisms].
AB  - INTRODUCTION: Cortical oscillatory activity has been related recently to
      information processing mechanisms. Synchronization between different neuronal
      groups can explain how he different features of an object can be integrated into
      a single perception (binding), or how different muscular groups can be co
      ordinated into a single movement. DEVELOPMENT: This paper reviews the knowledge
      up to date on the role of cortical oscillatory activity in perceptive binding and
      motor control. Also, the participation of alterations in cortical oscillatory
      activity in different neurological diseases (epilepsy, Parkinson's disease) is
      proposed, basing on available data. CONCLUSION: The study of the changes in
      cortical oscillatory activity (specially in the so-called gamma band 30-60 Hz)
      can contribute to current knowledge on the physiology and pathophysiology of the
      different cortical areas involved in perceptive and motor tasks.

PMID- 10919195
TI  - [Epidemiology of multiple sclerosis. Controversies and realities].
AB  - INTRODUCTION: Epidemiological studies of multiple sclerosis have given much
      information, although sometimes this is disconcerting and sometimes
      contradictory. The methodology used has to be improved and standardized in order
      to obtain studies which are comparable in different parts of the world.
      DEVELOPMENT AND CONCLUSIONS: Multicentric collaborating studies of similar ethnic
      groups under different environmental conditions may give significant key
      information regarding both pathogenic and trigger mechanisms. Epidemiological
      studies of multiple sclerosis, possibly modified by unknown environmental
      influences, have shown the importance of genetic susceptibility. The often quoted
      interrelation between prevalence and latitude still holds, although there are
      exceptions. Studies on incidence show that the disorder remains stable or is
      increasing, and most studies of prevalence show that this is increasing.

PMID- 10919196
TI  - [Genetic and environmental factors in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is expressed in genetically susceptible persons
      randomly affected by an unknown environmental factor, probably a virus, which
      sets off an abnormal immune process. DEVELOPMENT AND CONCLUSION: Race is an
      important predictive risk factor for multiple sclerosis, but genetics alone do
      not explain the occurrence of this disease. The genetic predisposition is
      complex, since several loci are involved in the susceptibility. Probably the
      immune process seen in multiple sclerosis is a consequence not a cause. The cause
      is possibly unique and due to infection. The causative agent may be rare or on
      the contrary may be frequent, but has different biological effects on susceptible
      persons. Epidemiology alone is not sufficient to find the cause. This requires
      collaboration from the basic sciences (genetics, microbiology, etc.). The results
      of epidemiological methods would be much improved if a biological marker for the
      disease was available.

PMID- 10919197
TI  - [The natural history of multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is one of the commonest idiopathic inflammatory
      diseases of the central nervous system in young adults. The study of the natural
      history of multiple sclerosis implies in the first place, establishing precise
      limits for the diagnosis of the disease, which is still of unknown origin. It is
      also necessary to analyze the wide range of varieties, which as different
      categories or subgroups and with different degrees of severity, make up the
      clinical spectrum of this entity. DEVELOPMENT AND CONCLUSIONS: Throughout this
      review benign and malignant multiple sclerosis, remitting and progressive forms,
      are studied from epidemiological and clinical points of view in the context of
      large populations of patients with multiple sclerosis on long-term follow up at a
      specialized centre, with the objective of finding, if possible, the patterns of
      the natural history of the disease.

PMID- 10919198
TI  - [Axonal involvement in multiple sclerosis. Current concepts].
AB  - INTRODUCTION: Axon pathology in multiple sclerosis is an emerging concept, not
      because it is unknown but because it has been forgotten. However, clinical,
      functional and pathological aspects have clearly shown that it is damaged at a
      very early stage in development of the plaque of demyelination. There is
      sufficient clinical, radiological and pathological evidence to permit definition
      of axonal damage as the central element of the pathology and clinical features of
      multiple sclerosis. DEVELOPMENT AND CONCLUSIONS: Throughout this article we will
      see how the axon is affected in multiple sclerosis, how this affects the
      inflammatory response and which parameters allow us to measure axonal damage and
      its relation to disability. Finally we will see how a new physiopathogenic
      concept of multiple sclerosis appears, based on the axonal lesion, and how this
      fits current clinico-pathological concepts better.

PMID- 10919199
TI  - [The use of biological markers in the diagnosis and follow-up of patients with
      multiple sclerosis. Test of five fluids].
AB  - PATIENTS AND METHODS: We studied five biological fluids which were easily
      accessible to immunological examination (cerebrospinal fluid, plasma, tears,
      saliva and urine) in 25 patients with multiple sclerosis, clinically definite
      according to the criteria of Cleveland, Ohio (1991) and tabulated according to
      the Kurztke's expanded disability status scale. The samples were obtained
      simultaneously during a clinical bout of the disease before any pharmacological
      or immunosuppressive treatment had been given. RESULTS: The soluble interleukin-2
      levels were significantly raised in at least three of these fluids--always absent
      from the urine--when compared with normal controls. The sensitivity and
      specificity of this determination for diagnosis of the condition was greater than
      that of other immunochemical parameters--oligoclonal distribution of
      immunoglobulins (specifically of IgG), imbalance of the light Kappa and Lambda
      chains--and physiological studies (evoked potentials). The dosification and
      quantification of basic myelin protein of the central nervous system, rich in
      citruline in the urine, may be a parameter of progressiveness. CONCLUSION: This
      methodology (five humours test) may be used to establish an earlier, more certain
      diagnosis of multiple sclerosis and also monitor its biological activity together
      with nuclear magnetic resonance with intravenous contrast.

PMID- 10919201
TI  - [Neuropsychological assessment in multiple sclerosis].
AB  - OBJECTIVE: Over the past 20 years great advances have been made in understanding
      the neuropsychological changes in multiple sclerosis. In this paper we review the
      nature of mental deterioration in multiple sclerosis and the procedures used for
      its evaluation. DEVELOPMENT: First we give a short summary of present knowledge
      of the involvement of different functions and the instruments most generally used
      to evaluate it. We then consider the different approaches to neuropsychological
      assessment, the use of broad guidelines as opposed to screening techniques,
      bearing in mind their advantages and disadvantages in the clinical field and in
      investigation. Similarly we mention the current trends in the evaluation and
      treatment of multiple sclerosis. CONCLUSIONS: The general profile of
      neuropsychological alterations in multiple sclerosis is characterized by the
      presence of changes in secondary memory and speed of thought, although the nature
      of this defect is still not clear. Changes are also seen in other
      neuropsychological functions, although less frequently and more controversially.
      Our knowledge of the prevalence of these changes comes from the use of guidelines
      for thorough examination. However, the current tendency is to seek instruments
      for evaluation which combine diagnostic efficiency, clinical usefulness and
      brevity. In this respect, although progress is being made, there are still
      questions to be answered.

PMID- 10919200
TI  - [Magnetic resonance in the clinical and therapeutic follow-up of multiple
      sclerosis].
AB  - Magnetic resonance is the most sensitive para-clinical method available for the
      diagnosis of multiple sclerosis since it shows changes in 95% of the patients
      with clinically definite multiple sclerosis. However, little correlation has been
      found, in different studies, between the parameters of magnetic resonance and the
      degree of neurological disability. The development and gradual application of new
      techniques of magnetic resonance, which permit specific detection of the lesions
      with the greatest degree of nerve dysfunction, permits improvement in the use of
      this technique for study of the natural history of the disease and thus to
      monitor patients given new treatments.

PMID- 10919202
TI  - [Urinary alterations in multiple sclerosis].
AB  - INTRODUCTION: The neurourological disorders of the lower urinary tract occur
      during the course of multiple sclerosis. Their expression as irritative,
      obstructive or mixed symptoms, in accordance with the standardized terminology of
      the International Continence Society, varies in each patient and also during the
      course of the illness of each patient. These vesicourinary disorders reduce the
      quality of life and their complications worsen the prognosis for survival if they
      are not suitably treated. DEVELOPMENT AND CONCLUSIONS: We review the anatomical
      and physiological basis integrating and coordinating vesical sphincter function;
      the dynamics of micturition with its phases of filling and emptying, their
      coordination with the sphincters through the different centres and circuits of
      the nervous system; the physiopathology, in relation to the localization of the
      plaques of demyelination, of incontinence due to detrusor hyperreflexia,
      hyperreflexia with dyssynergia, hyperreflexia of the detrusor with hypoactivity
      of the detrusor during the emptying phase and finally due to areflexia. The
      symptomatology and clinical features vary from 60% to 80% in the different series
      of cases, depending on the time of evolution and degree to which the patients are
      affected, with a predominance of irritative rather than obstructive symptoms. The
      treatment, which requires precise classification of the disorders, is with
      anticholinergic drugs or alpha 1 blocking and myorelaxant drugs, surgery,
      neurostimulators, rehabilitation, catheterism, the use of absorbent and
      collectors, other techniques and therapies which are being developed, without
      forgetting measures to prevent complications.

PMID- 10919203
TI  - [What treatment should be given for multiple sclerosis at the present time?].
AB  - OBJECTIVE: This communication aims to describe an approach suitable for the
      general neurologist or neurologist specialized in treating other disorders, to
      the current treatment of multiple sclerosis. DEVELOPMENT AND CONCLUSIONS: We
      discuss the treatments for recovery from the symptoms of an acute attack and
      those which modify the natural course of the illness (reduce the frequency and
      severity of attacks and/or prevent their progression). The attacks are treated
      with corticosteroids or ACTH. Both treatments have been shown on clinical trials
      to cause rapid improvement of the acute symptoms of an attack. In the progressive
      forms, the usefulness of high doses of corticosteroids has not been shown. Nor is
      there evidence that long term corticosteroid treatment, either daily or monthly,
      is of use in reducing the number of attacks or progression of the disease,
      although serious side-effects have been seen. At the moment, the interferons are
      the most popular treatment for multiple sclerosis. They have been the first drugs
      to modify the course of the disorder. Finally, we describe some of the most
      generally used treatments and some under investigation, although they are not
      widely used since it is still not clear exactly how they affect the course of the
      disease.

PMID- 10919204
TI  - [A historical description of the association of macro-orchidea, mental
      retardation and cranial dysmorphia in males (fragile X chromosome syndrome) by
      A.B. Richerand].
AB  - INTRODUCTION: Anthelme Baltasar Richerand practiced medicine as Chief Surgeon of
      the Hospital de S. Luis in Paris and was professor of the Faculty of Medicine of
      that city during the first quarter of the XIX century. His greatest work was
      titled Nouveaux Elements de Physiologie, a book considered to be the standard
      work on physiology of its time and was translated into several languages,
      including Spanish. DEVELOPMENT: In chapter CLV of this work there is the first
      description of associated macro-orchidia and mental retardation in males, with
      respect to three cases attended by the author. CONCLUSIONS: The fragile X
      chromosome syndrome is the commonest cause of hereditary male mental retardation
      associated with macro-orchidia. It is also known as the eponymous syndrome of
      Martin-Bell in honour of the first description published by these authors in
      1943. However, the first recognition of the association of macro-orchidia with
      mental retardation in males was by Richerand at the beginning of the XIX century.

PMID- 10919205
TI  - [Lateral bulbar infarct (Wallenberg syndrome) in nuclear magnetic resonance].

PMID- 10919206
TI  - [Primary progressive topographical amnesia: a new entity?].

PMID- 10919207
TI  - [The precaution principle and blood transfusion].
AB  - Because of the HIV and HCV virus transmission by transfusion during the eighties,
      there has been a retrospective reflection about the non-application of the
      precautionary principle, which has appeared only recently in the medical world.
      Since it was difficult to identify the real cause of the above-cited transmission
      in France, mainly because of the bad selection of blood donors, we feel we are
      justified in applying this precautionary principle more and more, in a
      monopolistic way, for biological security reasons. As a result, the biological
      research is not limited to looking for a 'degree zero' risk. Whether it concerns
      the 'PCR', the research of a new potential virus, the excessive fear regarding
      the transfusion of the new ESB agent, the worry caused by the blood donors who
      lived in the British Isles, the need for security based upon the precautionary
      principle is increasing endlessly. It is, however, more reasonable to consider
      that the precautionary principle should be essence incite a multi-disciplinary
      reflection involving biological sciences as well as social sciences. The
      precautionary principle would not make sense if it were not questioned for bad
      estimations, its harmful influences or its opportunistic use. Transfusion
      security, which is so important as a goal and as a principle, cannot appeal to
      the precautionary principle all the time, since the excessive use of this
      principle would lead to the paradox of not being able to identify the issues
      anymore.

PMID- 10919208
TI  - [Economic analysis versus the principle of guaranteed safety in blood
      transfusion].
AB  - This article shows that policies aimed at reducing risks of infectious agents
      transmissible through blood unfortunately follow a law of 'diminishing returns':
      increasing marginal costs have to be devoted for limited reductions in the risks
      of contamination through blood donations. Therefore, the economic cost
      effectiveness analysis is appropriate to identify screening strategies which may
      minimize costs to reach a certain level of safety. Moreover, economic analysis
      can contribute to public debates about the level of residual risk that society is
      willing to accept. Empirical results from French studies about screening for
      hepatitis C virus (HCV) in individuals who have received blood transfusions and
      in blood donations are presented to illustrate these points.

PMID- 10919209
TI  - [Dendritic cells and perspective on their therapeutic use].

PMID- 10919210
TI  - [The hemangioblast, common precursor of endothelial and hematopoietic cells].

PMID- 10919211
TI  - [Discovery of a chronic HVC infection without seroconversion in a blood donor in
      France during 28 months].
AB  - The HCV-RNA screening technique developed by the French Fractionation and
      Biotechnology Laboratory singled out in March 1998 a case of positive HCV-RNA
      viremia in a blood donor without any anti-HCV antibody. That donor was a 46-year
      old woman who had made 54 donations of blood products from 1988 to 1997. She had
      no history of blood transfusion, no history of hepatitis and no life-style risk
      factor. Clinical examination was normal. Liver tests (serum alanine amino
      transferases, gamma glutamyl transpeptidase , alkaline phosphatase, bilirubin ,
      prothrombin and albumin) were normal. Total blood count was normal. Lymphocyte
      count was normal as well as in vitro functional analysis of lymphocytes
      (stimulation with different antigens). All screening HCV Elisa tests and
      immunoblot System available on the French market were unable to detect anti-HCV
      antibodies. Quantification of serum HCV-RNA (Amplicor Monitor Roche) showed
      294,000 copies/mL and HCV genotype 1b determination was performed using Innolipa
      assay. Further examination of the HCV genotype by direct sequencing of the PCR
      product showed a classical 1b genotype sequence. The hemovigilance inquiry
      identified 25 labile products distributed since 1988. Analyzing the records of
      the recipients that have so far been traced and identified revealed three
      periods: 1997 to 1995: three recipients were found to be positive for anti-HCV
      antibodies; two are now cured of hepatitis C. In one recipient, direct sequencing
      after specific PCR of the hypervariable region coding for the envelope domain
      showed 100% homology with the donor; 1993 to 1990: four recipients were
      identified and traced without contamination; in 1988: three of four blood product
      recipients were anti-HCV negative without HCV-RNA viremia. The forth carried anti
      HCV antibodies and genotype 1b HCV-RNA but had a history of multiple surgery.
      Alter et al. [4] and Bush et al. [5] have previously suggested the possibility of
      a chronic, immunologically silent state of infection. The case described herein,
      is the first evidence for this hypothesis. Indeed, the donor has not yet
      seroconverted 28 months after viremia was discovered. This blood donor was
      identified by HCV-RNA screening of plasma products. The identification of the
      same sequence in a recipient of blood from this donor clearly establishes the
      transmission of the virus by transfusion. The prevalence of such cases of
      infectious silent chronic HCV carriers has to be determined and the mechanisms
      responsible for the absence of antibody production need to be clarified.

PMID- 10919212
TI  - [Clinical study of new blood products].

PMID- 10919213
TI  - [Allergic post-transfusion reactions].

PMID- 10919214
TI  - [Erythropoietin: current indications].

PMID- 10919215
TI  - [The current therapeutic bases for hemophilia].

PMID- 10919216
TI  - [Gene therapy of severe combined immunodeficiencies].

PMID- 10919217
TI  - [Viruses and unconventional transmissible agents: update on transmission via
      blood ].
AB  - The blood borne viruses must be separated into major and minor agents. Major
      viruses transmissible by blood transfusion are human immunodeficiency virus (HIV)
      and hepatitis B and C viruses (respectively HBV, HCV). The prevalence of
      virological markers in French blood donors has been continuously decreasing since
      the implementation of serological screening methods as soon as they were
      available. In 1998, the prevalences (per 10,000 donations) were 0.17 for antibody
      to HIV, 0.08 for antibody to human T-cell leukemia virus (HTLV), 2.23 for
      hepatitis B surface antigen (HBs Ag) and 2.52 for antibody to HCV. The values
      are, of course, higher in new donors when compared to regular donors:
      approximately five-fold for HIV, 50-fold for HCV and 300-fold for HBs Ag. The
      remaining major questions concern the residual risk due to infectious donations
      which could escape the preventive measures. It seems evident that the major risk
      is imputable mainly to donations collected during the window period. During the
      1996-1998 period, the residual risk for HIV was 1 out of 1,350,000 donations, 0
      for HTLV, 1 out of 375,000 for HCV, and 1 out of 220,000 for HBV. A few cases of
      "immunosilent" patients have been reported. They remain exceptional. The first
      data collected after the implementation of nucleic acid technology (NAT) confirm
      the very low residual risk. The recent introduction of leukodepletion probably
      brought an important contribution to diminishing the risk of transmission of
      leucotropic viruses such as cytomegalovirus (CMV), Epstein-Barr virus (EBV),
      human herpesviruses-6, -7 and -8, and HTLV. If the purification process of plasma
      derived medicinal products including inactivation procedures makes it possible to
      be confident with the elimination of infectivity due to enveloped viruses, the
      detection of nucleic acid sequences derived from naked viruses in plasma pools
      such as parvovirus B19 or hepatitis A virus (HAV), and/or the introduction of a
      nanofiltration step during the purification process, when possible, may greatly
      contribute to their safety. The emergence of a new form of the Creutzfeldt-Jakob
      disease (nvCJD) introduces a new series of questions about the safety of blood
      products that, although the risks appear limited, are not yet resolved.

PMID- 10919218
TI  - [Screening for viral genomes in blood transfusion].
AB  - Despite sustained improvement of donor selection and serologic screening assays,
      there still remains a small but significant transfusion risk for each of the
      major viral agents (hepatitis B virus [HBV], hepatitis C virus [HCV], human
      immunodeficiency virus [HIV] and human T-cell leukemia virus [HTLV]). The risk is
      due to the failure of the screening tests to detect all the infected blood
      donations and in particular those which are recently infected in the pre
      seroconversion window phase of infection, and the asymptomatic immunosilent
      chronic carriers who never develop antibodies. Another source of risk relates to
      variant strains of known viruses that are not detected by the current assays. The
      last potential risk involves the failure to detect infected blood samples because
      of inaccurate performances of the test process. In order to reduce this residual
      risk, the French health authorities requested the progressive introduction of
      nucleic acid technology (NAT) in blood screening so as to be generalised to all
      blood centres in the course of year 2000. Multicentric studies are underway to
      identify the most suitable techniques for the French network.

PMID- 10919219
TI  - [Screening tests combined with p24 antigen and anti-HIV antibodies in early
      detection of HIV-1].
AB  - The five available p24 Ag/anti-HIV combined tests were compared to the six third
      generation anti-HIV assays mainly used in blood transfusion centers. Among 70
      selected HIV-1 positive samples (12 samples from early infected blood donors and
      58 from ten commercial panels), 59 were positive with at least one assay. False
      negative results were observed for zero to six samples with p24 Ag/Ab assays
      versus seven to 19 with antibody (Ab) tests. In five cases, one or more combined
      assays gave a positive signal later than the most sensitive Ab screening test.
      One sample with a high p24 Ag titer was missed by one combined test. The mean
      time delay between the most sensitive test and the second one was 0.3 to 2 days.
      The p24 Ag limit of detection was investigated with seven dilutions of the HIV Ag
      reference. The threshold of the p24 Ag detection was found to be between 65 and
      250 pg/mL of HIV Ag. For four of the five combined assays, p24 Ag detectability
      was assessed with dilutions of infected culture cell supernatants from 13 HIV-1
      different genotype strains exhibiting HIV Ag titers from 300 to 450 pg/mL. One of
      the four combined assays gave negative results but close to the cut-off for three
      supernatant dilutions (1 B, 1 F, 1 HIV-1/O) and one missed the HIV-1/O dilution.
      The p24 Ag/Ab combined assays permit an earlier diagnosis of HIV infection than
      third generation assays even if the yield in terms of reduction of the window
      period is moderate. They are less sensitive than p24 Ag screening assays for the
      detection of this marker. Consequently, the p24 Ag/Ab assays have not been used
      for the diagnosis of a primary infection instead of p24 Ag screening tests. They
      must be considered only as good tools for the detection of HIV infection.

PMID- 10919220
TI  - [Interpretation of hepatitis C virus serology: immunoblot and genome
      amplification].
AB  - In France, screening for anti-hepatitis C virus (HCV) among blood donors has been
      performed since 1 March 1990. It is usually carried out using enzyme immunoassays
      (EIA). Positive or dubious results may be linked to false positive EIA reactions.
      Therefore the use of an immunoblot assay such as RIBA can be very useful to
      assess false positive signals. Moreover, the analysis of the different antibody
      reactivities makes it possible to evoke a viremic status or not. The follow-up
      provides essential information on recent seroconversion. However, some profiles
      do not allow a conclusion to be drawn between chronicity and serological sequel.
      In these cases, polymerase chain reaction (PCR) has to be implemented in order to
      conclude between the two.

PMID- 10919221
TI  - [Leukocyte depletion and infection by cytomegalovirus].
AB  - Cytomegalovirus (CMV) can be transmitted by fresh blood components containing
      leukocytes. Consequences of CMV infection are serious in immunocompromised
      patients and in neonates. Thus, prevention of transfusion-transmitted CMV is of
      paramount importance. The use of blood products from CMV seronegative donors has
      been shown effective in preventing transmission. However, it does not completely
      eliminate the risk of transmission. Moreover, as CMV seroprevalence reaches 50 to
      100% depending on the geographical and socioeconomic conditions, the availability
      of CMV seronegative products is limited. Leukodepletion of cellular blood
      products can be achieved by various filtration techniques. A method capable of
      achieving a residual leukocyte count < 5 x 10(6) per unit allows for the
      reduction of CMV transmission to a level at least equivalent to the transfusion
      of seronegative blood components. Moreover, leukodepletion may reduce endogenous
      virus reactivation. Administration of filtered blood products from CMV
      seronegative donors is usually recommended for those patients at major risk of
      severe CMV transfusion-associated disease. The ability of the most efficient
      methods for blood filtration in preventing CMV transmission has to be assessed.
      Such methods would make it possible to avoid serological screening of blood
      donors.

PMID- 10919222
TI  - [The field of erythrocyte immunohematology].
AB  - Biological tests and clinical practices are both required for the safety of
      donors and patients in immunohematology. Therefore, the objectives are to
      require: 1) biological analysis of anti-erythrocyte antibodies and antigens; 2)
      compatibility tests; 3) analysis for the biological qualification of blood
      donations; 4) genotyping; 5) qualitative and quantitative studies on antigens and
      antibodies; 6) clinical stages prior and after biological tests including systems
      of information, automation and computerization.

PMID- 10919223
TI  - [Trends in erythrocyte immunohematology reagents].
AB  - Until the 1980s blood group reagents had been produced from human or animal
      plasmas. Since then, the main change has been the increase of the use of
      monoclonal antibodies in laboratory reagents. Today, they are the basis of most
      reagents for blood group typing. They include murine (hybridomas) and human
      (Epstein-Barr virus immortalized lymphocytes and phage display) antibodies. The
      use of these antibodies leads to standardized methods of production and a better
      definition of the specificity through international works. The main drawback is
      the lack of antibodies for some blood group antigens. However, in the future
      these methods will be confronted with the development of DNA-based methods.

PMID- 10919224
TI  - [Evolving methods in immunohematology].
AB  - The immunogenic nature of erythrocyte polymorphism is in variance with the
      incompatible transfusion. Indeed, the fixing of an antibody on the corresponding
      antigen generally condemns the cell concerned with its destruction. Therefore, in
      order to ensure the immunohemolytic safety of the transfusions, it is necessary
      to avoid an in vivo encounter between antigens and antibodies, whose feasibility
      study in vitro is a determining element. Because of the requirement standards of
      such analyses and the preoccupation with the continuous improvement of
      transfusion safety, the evolution of the methods used in immunohematology is a
      constant concern for all those involved in the process. Thus, during the last few
      years, new technologies have been introduced which aim at improving performance
      and sometimes implementing alternatives to agglutination. This improvement is not
      limited to the search for an overall increase in specificity-sensitivity; it also
      takes into account the capability to detect "the clinically significant" as well
      as the limitations of human reliability, which justifies the introduction of
      automation and computerization. The whole of these methodological evolutions
      associated with that of the performance of reagents, legitimate the need to
      reconsider the realization of erythrocyte typing and the search for anti
      erythrocyte antibodies.

PMID- 10919225
TI  - [Analytical validation in erythrocyte immunohematology].
AB  - In a transfusional or foeto-maternal context, hemolysis by incompatibility due to
      anti-erythrocyte antibodies (regular or irregular) remains the most frequent and
      most serious immunological risk in the receiver. In order to prevent this risk, a
      number of actions must be taken, such as the realization of the immunohematologic
      analyses for which the methodological practices have been legislated because of
      their serious clinical consequences. Several elements play a role in the
      reliability of the analyses and their results: the selection of the reagents and
      their validation in the routine technique used; the validation of reception; the
      controls involved in secondary preparations (e.g., blood cells reagent); and the
      daily internal controls. All this requires the choice of adapted controls and the
      management of possible anomalies.

PMID- 10919226
TI  - [Blood transfusion and bacterial risk].
AB  - Initial hemovigilance data confirm the incidence and severity of transfusion
      reactions due to the bacterial contamination of blood components (TRBC). With 18
      deaths reported through the French hemovigilance network over the past 5 years,
      bacterial risks represent one of the major immediate complications of blood
      components (BC) transfusion. BC contamination may lead to more or less severe
      TRBC, depending on their origin: bacteria growth, the BC itself or unknown
      origin. Although the rate of donated blood or BC contamination is known (0.5% and
      0.05%, respectively) it is still difficult to assess the actual incidence of
      TRBC, as it is difficult to identify them and relate them to transfusion.
      Likewise, better knowledge of bacteria, symptoms and outcome is required to
      improve prevention methods. Better prevention can reduce BC contamination and
      proliferation of bacteria at each stage of blood transfusion. Methods to detect
      BC contamination are still under investigation. Through continuous education of
      hemovigilance actors in identifying and dealing with TRBC, as well as drawing up
      procedures to perform inquiries and specific bacterial analyses, case reporting
      can be further improved in order to achieve more efficient prevention.

PMID- 10919227
TI  - [Flow cytometry: applications in transfusion medicine].
AB  - In transfusion medicine, flow cytometry (FCM) is a methodology combining laser
      radiation, optics and a computerized treatment of numerous results. We can
      measure size, cellularity and fluorescence intensity of cells or particles in
      suspension after the binding of appropriate fluorescent antibodies or fluorescent
      dyes. The main utilisation of FCM in transfusion medicine is for quality control
      of the process of leukocyte reduction in red cell concentrates or in platelet
      units, using commercial kits. In addition, it is used for the enumeration of CD
      34 positive cells before bone marrow transplantation and for control of platelet
      function in platelet units. For clinical investigations, FCM may be used for red
      cell phenotyping, essentially to detect minor populations (chimerism), for the
      estimation of red cell survival, or for the detection of fetal erythrocytes. In
      the field of platelet immunology, FCM is an essential tool for detecting platelet
      antibodies (auto or allo), for platelet phenotyping or for cross-matching. In the
      future perhaps, FCM will permit us to detect bacterial contamination or prion
      protein in transfused blood cells.

PMID- 10919228
TI  - [Immunologic platelet tests].
AB  - Platelet immunological assays have been used for several decades. The
      antiglobulin consummation test was the first to be introduced followed by the
      immunoradiometric technique, immunofluorescence and enzyme linked immunological
      specific assay, as well as the different monoclonal antibody specific
      immobilisation of platelet antigens (MAIPA) assays. Using these different tests,
      it is possible to detect, quantify and define the specificity of platelet
      antibodies in neonatal alloimmune thrombocytopenia, in idiopathic
      thrombocytopenic purpura and post transfusion purpura.

PMID- 10919229
TI  - [Labile blood product traceability: definition, regulation, evaluation, and
      perspectives].
AB  - The traceability of blood products is an essential part of hemovigilance and
      transfusion safety. Law no 94-68 of 24 January 1994 is the legal foundation of
      the system of traceability. In this article, the structures of the system and the
      main actors are discussed. An evaluation of the system of traceability showed
      that it is both feasible and adaptable. An evaluation process is needed to assess
      the proper functioning of the system and to detect and prevent possible
      deficiencies.

PMID- 10919231
TI  - [Analysis of an information network].
AB  - This study, performed in the Loire-Atlantique region, gives a full list of the
      positions responsible for the transfer of information and the methods of
      implementation. It demonstrates that mobile blood collection units and numerous
      blood donor associations, although in close contact with donors, represent the
      weak link in the information network. This weakness has its origins in a lack of
      communication with the central sources of information, and in the absence of
      participation in various projects. The study emphasizes the importance of
      communication in addition to the responsibilities of the members of the
      organization.

PMID- 10919230
TI  - [Audit of labile blood product supplies].
AB  - An audit of the quality control system is part of an ongoing improvement process.
      The hospital-based facilities for the transfusion services not involved in
      collecting and processing donor blood but issuing blood cell products are
      expected to achieve quality standards. A quality control audit is considered an
      essential tool to assess and improve deficiencies or deviations for greater
      effectiveness. A global approach to transfusion processes added to a strict
      follow-up by all concerned are necessary for the proper management of transfusion
      practices and the risks involved. Its function is to achieve a certain quality of
      health, thus requiring confidence and respect. The end result is to ensure blood
      transfusion safety.

PMID- 10919233
TI  - ["Saarland growth study"].

PMID- 10919232
TI  - [The physician's role in blood donation].
AB  - In France, proper transfusion practices impose that the medical pre-donation
      interview be done by a physician. In Anglo-Saxon countries, it is more often
      performed by a nurse. The physician's job is not limited to the clinical
      selection of blood donation volunteers. In the production process, the physician
      is implicated in the safety and supply of labile blood products. The practice of
      the profession requires educational and communication skills. As the manager of a
      medical team working in mobile sites, the physician must ensure the respect of
      ethics and professional regulations by the staff he or she trains and supervises.

PMID- 10919234
TI  - [Reference values for body height and weight of German children-- introduction].

PMID- 10919235
TI  - [Saarland Growth Study: sampling design].
AB  - The use of reference data to evaluate the physical development of children and
      adolescents is part of the daily routine in the paediatric ambulance. The
      construction of such reference data is based on the collection of extensive
      reference data. There are different kinds of reference data: cross sectional
      references, which are based on data collected from a big representative cross
      sectional sample of the population, longitudinal references, which are based on
      follow-up surveys of usually smaller samples of individuals from birth to
      maturity, and mixed longitudinal references, which are a combination of
      longitudinal and cross-sectional reference data. The advantages and disadvantages
      of the different methods of data collection and the resulting reference data are
      discussed. The Saarland Growth Study was conducted for several reasons: growth
      processes are subject to secular changes, there are no specific reference data
      for children and adolescents from this part of the country and the growth charts
      in use in the paediatric praxis are possibly not appropriate any more. Therefore,
      the Saarland Growth Study served two purposes a) to create actual regional
      reference data and b) to create a database for future studies on secular trends
      in growth processes of children and adolescents from Saarland. The present
      contribution focusses on general remarks on the sampling design of (cross
      sectional) growth surveys and its inferences for the design of the present study.

PMID- 10919236
TI  - [Saarland Growth Study: analyses of body composition of children, aged 3 to 11
      years. Measurement of height, weight, girth (abdomen, upper arm, calf) and
      skinfolds (triceps, biceps, subscapular,suprailiacal, abdominal) and bioelectric
      impedance (BIA)].
AB  - This study aimed to set up current reference charts of anthropometric data in the
      Saarland. Only national and international data were available to be compared but
      no former Saarland charts could be found. In the period between 1994 and 1995 we
      investigated children of 3 to 11 years in a cross-sectional study. Therefore we
      measured body height, weight, circumferences, skinfolds and bioelectrical
      impedance (BIA). No significant gender differences were found for body height and
      weight. Boys of all groups of age showed bigger abdominal circumferences than
      girls of the same age. On the other hand upper-arm and calf-girth of younger
      girls were larger than that from boys. In higher age groups circumferences become
      rather equal. The skinfolds of Saarland girls are thicker than those of boys. The
      urban rural comparison indicated no significant differences. Nor was any social
      divergence found among the aforementioned parameters. Regarding height Saarland
      children are seen to be similar or somewhat shorter than those examined in
      national or international studies. By the way, in higher percentiles the children
      in our study were heavier. Thus high BMI values of our study are bigger compared
      with former studies. According to the definition of obesity by the ECOG almost 20
      to 30% of our children are obese. The older children become the higher is the
      percentage of obesity. Comparing girls and boys, bioelectrical impedance shows
      higher values for girls. In higher age classes resistance levels gets smaller, in
      boys more so than in girls. Body fat estimated by a formula based on BIA test
      parameters yielded negative values. So we propose the use of sex- and age
      specific raw charts of BIA test parameters.

PMID- 10919237
TI  - [Saarland Growth Study: percentile charts for height, weight, and body mass index
      (BMI) for boys and girls, 4-18 years old, in Saarland].
AB  - In a cross-sectional study dating from april 94 to march 96 we have investigated
      length and weight of 2610 girls and 2865 boys (age 4-18 years) at nursery schools
      and schools in Saarland. Thus we could provide first normative data for this
      region of Germany. Compared with data that have been collected between 1968 and
      1989 at Dortmund, Bonn, Hamm and Jena, we found an increase in height of 2 cm for
      girls and boys aged 15-18 years. Apart from this finding, no further differences
      have been observed. Compared with international data, 18-year-old females and
      males in Saarland show large body heights: their average heights were 169 and 182
      cm, respectively. Unfortunately, body weight of children of the Saarland is high,
      too. Children in Saarland were on average 1.5-6.6 kg heavier than those of the
      Dortmund study or other international studies. Studies have revealed that,
      according to the ECOG criteria, people of the Saarland are more obese than in
      other European countries. As a consequence of our study we request an institution
      for auxology to be founded which enables immediate reaction. This not only
      implies medical view points but also practical aspects of daily life (e.g. height
      of chairs or tables at schools). It is important to note that no changes have
      been made so far. Standards for height and weight should be updated every ten
      years. This should be a collaborative task between public health services and
      pediatric endocrinologists.

PMID- 10919238
TI  - [Treatment of the incurably ill].
AB  - Modern medicine has a) drastically prolonged the average lifetime, and b) dying
      from a relatively brief transition phase, has in many cases become a long-lasting
      process. This demands an increased orientation of medicine, away from the pure
      goal of "healing" to the task of a long-lasting accompaniment. This means
      geriatric rehabilitation and ultimately accompaniment for the dying. New ethical
      and juridical problems arise thereof for the doctor which will be discussed here.
      However, also society is challenged. We need systematic installment of
      rehabilitation activities into nursing homes, and a rehabilitation insurance.

PMID- 10919239
TI  - [Cartilage damage--the chameleon problem of the knee joint].

PMID- 10919240
TI  - [The effect of arthroscopic joint debridement in advanced arthrosis of the knee
      joint].
AB  - A retrospective study was performed examining 84 patients who had undergone
      arthroscopic debridement for high-grade osteoarthritis of the knee joint. After
      an average follow-up period of 52 (35-72) months only 14 (16.7%) patients
      indicated an improvement of the preoperative situation. 36 (42.8%) patients had
      severe joint pain after one year postoperatively. 17 (24.3%) patients were
      evaluated with 85-100 points and 53 (75.7%) patients with less than 85 points in
      a modified Lysholm-score. There were better results in younger patients (< 50
      years). Compared with the literature, aggressive subchondral abrasion does not
      show any benefits. Patients' preoperative expectations have to be clearly
      objectified. With this prerequisite the surgical procedure as an operation with
      low complication risk can also be justified as a temporary alternative to total
      knee arthroplasty in patients suffering from a high-grade degeneration of the
      knee joint.

PMID- 10919241
TI  - [Experiences with arthroscopic therapy of chondral and osteochondral defects of
      the knee joint with OATS (Osteochondral Autograft Transfer System)].
AB  - Between 1.6.1997 and 31.12.1998 an osteochondral transplantation with the OATS
      (Osteochondral Autograft Transfer System) was performed in 18 patients.
      Indication for OATS was in 9 cases a chondral defect in ACL deficient knees. 3
      times we found a fresh chondral defect, in 6 cases we found cartilage damage on
      the medial femoral condyle at the main weight-bearing area (Outerbridge, type III
      IV) in chronic ACL deficient knees. The defect-size in these 9 patients (7 male
      and 2 female) ranged between 12 mm and 23 mm in diameter and had an average-size
      of 15 mm. There have been 3 cases with osteochondrosis dissecans, 4 patients had
      a osteonecrosis at the medial femoral condyle. In the 18 cases an average of 1.8
      grafts was needed; more than 3 grafts were used only in exceptional cases,
      because in such cases the stability between the grafts is reduced. The short
      outcome in the Lysholm-score showed mainly good results. The average score value
      during follow-up was 89.5 (range 78-92). This outcome makes hopeful for likewise
      middle-term-results. The OATS can be recommended for the treatment of chondral
      and osteochondral defects in the main-weight-bearing area of the knee as a safe
      procedure for transplantation of hyaline cartilage.

PMID- 10919242
TI  - [Microfracture for treatment of cartilage detects].
AB  - Subchondral bone plate microfracture technique (Steadman) has shown to enhance
      chondral resurfacing by providing a suitable environment for tissue regeneration
      and taking advantage of the body's own healing potential. Microfracture technique
      belongs to the bone marrow stimulating methods like abrasion arthroplasty or
      subchondral bone drilling. Using a specially designed awl or pick, multiple
      perforations ("microfractures") are placed 3 to 4 mm apart and about 4 mm deep
      into the subchondral bone to reach a zone of vascularization. The formation of a
      fibrin clot ("super clot") containing the desired pluripotential stem cells is
      stimulated. This clot then differentiates and remodels, resulting in a durable
      fibrocartilage repair tissue. The arthroscopic awls produce essentially no
      thermal necrosis of the bone compared to hand-driven or motorized drills. In
      contrary to drills, it is possible with differently curved awls to reach and
      treat every area of the knee joint or even of the upper ankle or shoulder joint.
      Between 1992 and 1998 this technique has been used in 351 cases. 162 patients
      were interviewed with a questionnaire with respect to their subjective judgement
      of health between 3 and 6 years (mean 4.4) after operation. Pain was the
      parameter with the greatest improvement. 78% of the patients improved, 18%
      remained unchanged and 4% were worse. Microfracture is an advisable option for
      the treatment of full thickness chondral defects.

PMID- 10919243
TI  - [Autologous lateral patellar transplant as a reserve method for managing large
      osteochondral defects of the knee joint in young adults].
AB  - Between 1995 and 1997, five patients were operated on with a large osteochondral
      defect of the femoral condyle using the lateral third of the patella. The age of
      the four male and one female ranged from 18 to 23 years. Initially all of them
      suffered from an osteochondrosis dissecans which was located at the typical site
      on the medial condyle of the femur, in the maximal weight bearing region. The
      follow-up study was 14 to 35 months and showed an improvement from 35 points
      preoperatively to 89 points postoperatively based on the Cincinnati knee score.
      All patients returned to there previous profession as well as mild sports
      activity. The postoperative examination did not show any retropatellar problems
      and there were no radiological signs of the femoropatellar joint osteoarthritis.
      For the operative treatment of large chondral defects at the femoral condyle
      autologous osteochondral transplantation using the lateral third of the patella
      seems to be a successful alternative.

PMID- 10919244
TI  - [Tissue engineering for therapy of osteochondral cartilage lesions].
AB  - Cartilage defects still represent an unsolved problem in joint surgery. The
      intrinsic healing capacity of cartilage is insufficient and at best leads to
      reparative tissue like fibrous cartilage or cartilage like tissue regardless of
      the therapy applied. Cell culture techniques and generation of tissue specific
      matrix tread new paths to treat traumatic cartilage lesions. This technology
      referred to as tissue engineering allows for formation of constructs consisting
      of chondrocytes capable of production of cartilage specific matrix in combination
      with three-dimensional cell carriers. Polymers such as polylactid, co-polymers
      like polydioxanon with polyglactin and lyophilized dura have been used
      successfully to create such constructs with chondrocytes of different animal
      species. Cartilage specific compounds can be detected by histological and
      immunohistochemical techniques. To apply these constructs in humans, the
      distinguishing characteristics and problems of cell culture with human
      chondrocytes have to be considered. A further improvement of the artificially
      created tissue is conceivable using growth factors even including genetic
      manipulation of the applied cells.

PMID- 10919245
TI  - [Autologous chondrocyte transplantation for treatment of cartilage defects of the
      knee joint. Clinical results].
AB  - Cartilage defects in the knee joint are common and have a bad tendency for
      healing due to the limited regeneration of hyaline cartilage. Surgeons have an
      ample choice of various operative treatment measures. Especially for the
      treatment of larger lesions first results of autologous chondrocyte
      transplantation (ACT) were published in 1994 [3]. Autologous chondrocytes are
      isolated from an arthoscopically harvested cartilage biopsy, cultured in vitro
      and implanted in the defect under a periostal flap in a second procedure. In an
      international multicenter study 1,051 patients treated with ACT between 6/95 and
      12/98 were documented with follow-up examinations after 12 months (588 patients),
      24 months (220 patients) and 36 months (40 patients). The majority of the defects
      (61.2%) were localized on the medial femoral condyle, measuring 4.6 cm2 and
      mostly described as grade III/IV lesions. The clinical evaluation was performed
      using a modified Cincinnati knee rating system independently for clinician and
      patient. Evaluations showed an increase from 3.35 to 6.25 after 24 months and
      from 3.10 to 6.77 in a scale from 1 (bad) to 10 (excellent). ACT favours defects
      of the femur with an improvement rate of 85%. Adverse events possibly related to
      ACT were described in 4.8% of the patients. Diagnostic second-look arthroscopies
      are included in the reoperation rate of 5.1%. The presented data indicate
      autologous chondrocyte transplantation as an effective and safe option for the
      treatment of large full thickness cartilage defects in the knee joint.

PMID- 10919246
TI  - [Para-articular knee osteotomies].
AB  - Osteotomy close to the knee is an established method to treat degenerative
      osteoarthritis of the knee with varus or valgus deformity. However, indications,
      surgical techniques and results are discussed controversially. This article gives
      an overview of those surgical procedures most commonly used for correcting valgus
      and varus deformities. Supported by our results it is shown that osteotomy of the
      tibia for degenerative osteoarthritis together with operative arthroscopy in the
      same operative session gives better results compared to osteotomy alone. Despite
      the success of arthroplasty of the knee, osteotomy has it's place in the
      treatment of osteoarthritis.

PMID- 10919247
TI  - [Can meniscus refixation prevent early development of arthrosis in the knee
      joint? Long-term results].
AB  - This retrospective study presents the long-term results after meniscal repair
      with emphasis on early-development of osteoarthritis in the knee. From 1984 to
      1996 meniscal repair using the inside-out technique was performed on 54 patients.
      25 patients had an isolated tear of the meniscus and 29 additionally a tear of
      the anterior cruciate ligament (ACL, combined injury). 18 patients of those with
      a combined injury showed a stable knee during clinical follow-up. A separate
      evaluation of this group was carried out. The mean follow-up was 6.4 years. 22
      patients were examined over a period of 2-5 years (mean 3.5) after surgery, 32
      patients after 5 years (mean 8.9). The clinical evaluation was carried out using
      IKDC, Tegner activity scale, Lysholm, and Tapper and Hoover-Score as well as the
      Fairbank radiographic evaluation. According to the Fairbank's evaluation the
      results show that up to 5 years after meniscal repair only minimal radiographic
      changes were detectable. In only 21% of patients with an isolated meniscal lesion
      and in 13% of those with a stable knee after a combined injury beginning of
      osteorathritic changes were noted more than 5 years postoperatively. Early
      osteoarthritic changes were present within 5 years after surgery in non-stable
      knees (untreated rupture, suturing). Patients with meniscal repair mostly regain
      their original Tegner activity level and good to very good results in the
      clinical scores. However, the results clearly indicate that the success of
      meniscal repair depends on the stability of the knee. Thus, meniscal repair in
      stable knees is recommended to prevent early development of osteoarthritis.

PMID- 10919248
TI  - [Joint loading as a possible etiology for arthrosis development. Results of
      animal experiment studies of the rat model].
AB  - We review our results with an animal model for investigations on the development
      of osteoarthritis (OA). This model is based on running exercises of wistar rats
      performed in a running wheel using intracranial self-stimulation to motivate rats
      to excessive running. In our studies a total of 49 rats was divided into groups
      with running exercises of 15 km, 20 km, and 30 km respectively. In order to
      investigate the influence of altered sensible joint innervation on the
      development of OA, in addition to a total running load of 20 km in another group
      of 8 rats we performed Capsaicin (8 Methyl-N-vanillyl-6-noneamide) mediated
      partial sensible knee joint denervation. Complete knee joint sections of all rats
      were evaluated histologically using Mankins grading system. In addition, we
      performed semiquantitative assessment of the immunoreactivity of the chondrocytes
      to MMP-3 by immunostaining with monoclonal MMP-3 IgG antibodies. Histological
      assessment and immunostaining for MMP-3 of the knee joint sections revealed a
      significant increase in osteoarthritic changes with higher running load.
      Moreover, osteoarthritic changes in the knee joints of the rats with sensible
      joint denervation and running exercises were significantly greater as compared to
      those with sole running load. In conclusion, our studies revealed a significant
      relationship between the development of knee osteoarthritis and the extent of
      joint load. Hereby, an alteration of the sensible joint innervation seems to have
      a promoting effect on the development of osteoarthritic changes. This model
      offers a wide range of further approaches to studying different processes of the
      development of OA.

PMID- 10919249
TI  - [Rare, but severe complication of varicose vein surgery. Compartment syndrome].
AB  - The compartment syndrome is an extremely rare complication after varicose vein
      surgery. If the early symptoms are not recognized and a treatment is not
      performed immediately most patients lose sensomotory function. Three cases with
      compartment syndrome after varicose vein stripping were the reason to point out
      the anatomy and pathophysiology of this complication and to explain the surgical
      technique.

PMID- 10919250
TI  - ["Acute cholecystitis"--laparoscopic cholecystectomy is often possible. Results
      of a multicenter study by the East German Study Group for Performance Assessment
      and Quality Assurance in Surgery].
AB  - With the introduction of laparoscopic cholecystectomy (LCE) the method became
      very fast successful in clinical practice. To describe the actual situation we
      initiated in 1994/95 a clinical multicenter study with the name CESAQ. 29
      hospitals participated in the study. 4,675 cholecystectomies were performed, a
      total number of 2,960 patients were operated upon with the laparoscopic and 1,468
      with the conventional technique. Furthermore, conversion to open cholecystectomy
      was necessary in 247 cases. One part of the study focused on the results achieved
      for patients with acute cholecystitis. 9.4% of the laparoscopic but 37.3% of the
      conventional cholecystectomies were performed due to acute cholecystitis. We
      differentiated a simple (adhesions to gallbladder, hydrops) and complicated form
      (empyema, gangrenous gallbladder) of acute cholecystitis. Treating acute cases
      the incidence of intraoperative (simple 8.3%, complicated 12.1%) and specific
      postoperative complications (simple 9.2%, complicated 6.9%) was higher compared
      to elective procedures (intraoperative 4.6%, specific postoperative 3.7%). This
      is well known from the experience of open surgery. Nevertheless there were lower
      general complication rates (simple 5.5%, complicated 5.2%) and no mortality in
      acute cholecystitis when LCE was performed. Considering an early conversion to
      open cholecystectomy in cases of severe acute cholecystitis the indication for
      LCE can be made generously. Great surgical experience in LCE is a requirement for
      the laparoscopic management of acute cholecystitis.

PMID- 10919251
TI  - [Life and work of the surgeon Ernst von Bergmann (1836-1907), long-term editor of
      the "Zentralblatt fur Chirurgie"].
AB  - Ernst von Bergmann (* December 16, 1836 at Riga- [symbol: see text] March 25,
      1907 at Wiesbaden) was one of the most famous and successful surgeons in Europe
      at the end of the 19th century. Having passed his medical education at the
      University of Dorpat/Latvia he did his doctorate on a pharmacological subject and
      habilitated as a young assistant already in 1863 with a well-founded experimental
      study on animals to the question of fat embolism. The voluntary participation as
      medical officer in three wars (1866, 1870/71, 1877/78) gave him the qualification
      to express important logistic conditions for the case of vast numbers of wounded
      soldiers, to demand an increased deployment of better trained ancillary and
      nursing staff as well as to establish a modified procedure for the treatment of
      gunshot wounds, particulary of the joints and the skull. In his position as
      regular professor and head of the surgical department at the Universities of
      Dorpat (1871-1878), Wurzburg (1878-1882) and Berlin (1882-1907) he redressed
      quickly architectural and infrastructural mismanagements despite of complex
      obstacles, spoke up for a diversified education of the students he has been
      entrusted with, supported untiringly the career path of his collaborators and
      published a huge number of internationally approved scientific articles. In
      addition to his very time-consuming clinical activities, which even took him to
      the highest social classes, von Bergmann became initiator of the surgical asepsis
      and developed operative methods valid up to this day in traumatology, abdominal,
      tumour and, above all, in neurological surgery. Being member or chairman of
      different medical associations and editor of prestigious periodicals, he started
      an effective post-graduate training for interested colleagues and arranged the
      first qualified exhaustive rescue service in the German capital.

PMID- 10919252
TI  - [In Process Citation]

PMID- 10919253
TI  - [Basic principles in surgical oncology (2)].

PMID- 10919254
TI  - The corticotropin-releasing hormone system and feeding behavior--a complex web
      begins to unravel.

PMID- 10919255
TI  - Modulation of urocortin-induced hypophagia and weight loss by corticotropin
      releasing factor receptor 1 deficiency in mice.
AB  - Intracerebroventricular injection of CRF or urocortin (Ucn) reduces appetite and
      body weight. CRFR1 and CRFR2, the receptors for CRF and Ucn, are expressed in
      neurons associated with appetite-control and metabolism, but their relative
      contributions in mediating CRF- or Ucn-induced hypophagia and weight loss are not
      known. We used homozygous mice lacking CRFR1 (CRFR1-/-) and wild-type littermates
      to determine the role of CRFR1 in mediating the changes in food intake and body
      weight following intracerebroventricular administration of Ucn. CRFR1-/- mice,
      which are glucocorticoid deficient, were given corticosterone in their drinking
      water to induce diurnal variations in circulating corticosterone. A 7-day
      intracerebroventricular infusion of Ucn transiently suppressed ad libitum food
      intake equally in CRFR1-/- and wild-type mice. Body weight reduction during Ucn
      infusion paralleled food intake in wild-type mice, but persisted throughout the
      infusion in CRFR1-/- mice. After food-deprivation, acute intracerebroventricular
      injection of Ucn suppressed food intake for 1.5 h in wild-type mice. By contrast,
      CRFR1-/- mice did not respond to Ucn 1.5 h after injection. At later time points,
      Ucn suppressed food intake equally in both genotypes. The distinct time courses
      of CRF-receptor-induced hypophagia suggest that separate pathways act
      cooperatively to adjust food intake during challenges to homeostasis.

PMID- 10919256
TI  - Ovary-selective genes I: the generation and characterization of an ovary
      selective complementary deoxyribonucleic acid library.
AB  - The importance of several ovary-selective/specific genes, i.e. genes
      preferentially or exclusively expressed in the ovary, has been established.
      Indeed, null mutant female mice for the c-mos, growth and differentiation factor
      9, alpha-inhibin, and zona pellucida-3 genes proved sterile. A loss of function
      mutation of the human FSH receptor gene established its critical role in ovarian
      function. These data support the hypothesis that genes expressed selectively or
      specifically in the ovary are probably essential for the normal functioning of
      this organ system. We have used the differential screening technique suppression
      subtractive hybridization to systematically isolate and clone genes that are
      expressed in an ovary-selective/specific manner. The resultant target
      complementary DNA (cDNA) library has been exhaustively screened to a point at
      which additional sequencing was increasingly unlikely (< or = 4%) to yield
      additional previously unencountered cDNAs. In toto, 844 clones were sequenced and
      analyzed for homology to known genes using the Basic Local Alignment Tool
      (BLAST). Of those, 342 were determined to be independent (nonredundant). One
      hundred and fifty-nine independent clones proved identical to previously
      characterized genes, whereas an additional 100 independent clones proved
      significantly homologous (but not identical) to previously characterized genes.
      Yet 83 other independent clones did not display significant homology to
      previously characterized genes now listed in the publicly accessible nonredundant
      databases. As such, these latter genes were deemed novel. Of these 83 novel
      genes, a total of 36 displayed ovary-specific/selective expression, as determined
      by probing mouse multitissue Northern blots with 32P-labeled/PCR-amplified cDNA
      inserts. Under these circumstances, the false positive rate was minimal, as only
      one novel clone was expressed at a higher level in nonovarian tissues relative to
      ovary. Of the 36 ovary-specific/ selective novel genes, 22 proved subject to
      hormonal regulation during a simulated estrous cycle. In this communication we
      focus on 2 such novel ovary-specific/hormonally-dependent genes, the full-length
      sequences of which were isolated using rapid amplification of 3'-cDNA ends
      technology. Taken together, the present study accomplished systematic
      identification of those genes that are restricted in their expression to the
      ovary. These ovary-selective genes may have significant implications for the
      understanding of ovarian function in molecular terms and for the development of
      innovative strategies for the promotion of fertility or its control.

PMID- 10919257
TI  - Interactive stimulation by luteinizing hormone and insulin of the steroidogenic
      acute regulatory (StAR) protein and 17alpha-hydroxylase/17,20-lyase (CYP17) genes
      in porcine theca cells.
AB  - LH and insulin are postulated to jointly stimulate theca-cell androgen
      biosynthesis in patients with hyperthecosis or polycystic ovarian syndrome. To
      explore the mechanisms of putative LH and insulin steroidogenic synergy in
      primary culture of normal theca cells, we have implemented an in vitro serum-free
      monolayer culture system of Percoll-purified, porcine theca cells harvested from
      immature ovaries. Initial dose and time course analyses revealed that a maximally
      effective concentration of LH (100 ng/ml) or insulin (100 ng/ml) individually
      will drive androstenedione production (at 6 to 48 h) by 1.5- to 2.6- and 1.1- to
      1.7-fold, respectively, while combined agonists act synergistically over the
      interval 12 to 48 h yielding a 3- to 4-fold joint effect. Coadministration of LH
      and insulin can augment theca-cell concentrations of CYP17 and StAR messenger RNA
      (mRNA) resulting in 3.4- to 3.9- and 3.8- to 4.1-fold increases at 24 to 48 h,
      respectively (P < 0.01). Combined LH and insulin stimulation also amplified the
      nuclear content of intron-specific heterogeneous nuclear (hn)RNAs encoding CYP17
      and StAR. Insulin significantly enhanced LH-driven but not basal cAMP
      accumulation (14-18 vs. 3-5.5 pmol/microg DNA/12-48 h) (P < 0.01). A stable
      exogenous analog of cAMP, 8 Br-cAMP, mimicked LH's effect on steroidogenesis and
      StAR and CYP17 gene expression and with insulin stimulated StAR mRNA and hnRNA
      accumulation synergistically. However, unlike LH, 8 Br-cAMP did not synergize
      with insulin on theca-cell androstenedione biosynthesis or CYP17 mRNA and hnRNA
      expression. In summary, the present in vitro data identify molecular interactions
      of LH and insulin on StAR and CYP17 gene expression, thus establishing potent
      signaling interfaces between these distinct hormonal agonists in regulating theca
      cell steroidogenesis.

PMID- 10919258
TI  - Insulin-like growth factor I reduces ubiquitin and ubiquitin-conjugating enzyme
      gene expression but does not inhibit muscle proteolysis in septic rats.
AB  - We examined the effect of insulin-like growth factor I (IGF-I), administered in
      vivo, on protein turnover rates and gene expression of the ubiquitin-proteasome
      proteolytic pathway in skeletal muscle of septic rats. Sepsis was induced by
      cecal ligation and puncture. Other rats were sham-operated. Miniosmotic pumps
      were implanted sc, and groups of rats received IGF-I (7 mg/kg x 24 h) or saline.
      Protein synthesis and breakdown rates were determined in incubated extensor
      digitorum longus muscles. Messenger RNA levels for ubiquitin and the ubiquitin
      conjugating enzyme E2(14k) were determined by Northern blot analysis. Sepsis
      resulted in an approximately 30% reduction of muscle protein synthesis, and this
      effect of sepsis was blunted in rats treated with IGF-I. In contrast, IGF-I did
      not prevent the sepsis-induced increase in total and myofibrillar muscle protein
      breakdown. Ubiquitin and E2(14k) messenger RNA levels were increased several fold
      in muscle from septic rats, and this effect of sepsis was abolished in IGF-I
      treated rats. The results suggest that administration of IGF-I may improve sepsis
      induced muscle cachexia by stimulating protein synthesis. However, because
      muscles were resistant to IGF-I, with regard to regulation of protein breakdown,
      the use of IGF-I to treat muscle cachexia during sepsis remains unclear. An
      additional important implication of the present study is that changes in
      messenger RNA levels for ubiquitin and the ubiquitin-conjugating enzyme E2(14k)
      do not always reflect changes in muscle protein breakdown rates.

PMID- 10919259
TI  - Islet blood flow in multiple low dose streptozotocin-treated wild-type and
      inducible nitric oxide synthase-deficient mice.
AB  - The present study tested the hypothesis that changes in islet blood perfusion
      occur during the development of diabetes in the multiple low dose streptozotocin
      treated mouse. Streptozotocin (40 mg/kg) or citrate buffer was given ip once
      daily for 5 consecutive days to wild-type and inducible nitric oxide synthase
      (iNOS)-deficient C57BL/6 x 129 SvEv hybrid mice. The blood flows were then
      determined by a microsphere technique. The islet blood perfusion was almost 2
      fold higher in wild-type mice treated with streptozotocin than in those given
      vehicle. Whole pancreatic blood flow was also increased in the streptozotocin
      treated wild-type mice. In iNOS-deficient mice, neither islet blood flow nor
      whole pancreatic blood flow was affected by repeated streptozotocin treatment.
      These combined findings suggest an increased islet blood perfusion in the
      prediabetic stage mediated by an iNOS-dependent mechanism. In combination with
      increased vasopermeability and expression of adhesion molecules on the islet
      endothelium, as previously described, this increased islet blood flow may be of
      crucial importance for the recruitment of inflammatory cells into the islets
      during the development of diabetes in this animal model. Indeed, an increased
      degree of insulitis was observed in wild-type mice compared with mice deficient
      in iNOS as well as a more rapid decrease in islet volume and an earlier debut of
      manifest diabetes. We also describe altered islet blood perfusion in the iNOS
      deficient mice during basal conditions due to a compensatory increase in
      constitutive NOS activity.

PMID- 10919260
TI  - Role of winged helix transcription factor (WIN) in the regulation of Sertoli cell
      differentiated functions: WIN acts as an early event gene for follicle
      stimulating hormone.
AB  - Members of the winged helix transcription factor family are known to regulate
      epithelial cell differentiation by regulating cell-specific gene expression. rWIN
      is a newly discovered member of the winged helix family shown to be present in
      the adult rat testis. In the testis the human homolog of rWIN, HFH-11, was
      localized to the germ cells (i.e. spermatocytes and spermatids) undergoing
      spermatogenesis. In the present study we show that rWIN is also expressed in
      testicular Sertoli cells. Sertoli cells are the epithelial component of the
      seminiferous tubule and provide both the cytoarchitectural support and the
      microenvironment for developing germ cells. The presence of rWIN in Sertoli cells
      was confirmed by Northern blot and RT-PCR analysis. The rWIN transcript size in
      the Sertoli cells was different from the germ cell transcript that is probably
      due to alternative splicing or modifications of the 3'-untranslated region. At
      least two spliced variants of rWIN were observed in the Sertoli cells
      corresponding to the deletion of an exon in the DNA-binding region. Long term
      stimulation of cultured Sertoli cells with the gonadotropin FSH down-regulated
      rWIN expression. In contrast, short-term stimulation (2 h) transiently up
      regulated rWIN expression. The FSH-induced transient stimulation of rWIN precedes
      expression of the transferrin gene that is a marker of Sertoli cell
      differentiation. FSH-induced transferrin promoter activity was inhibited when
      cultured Sertoli cells were treated with an antisense oligonucleotide to rWIN.
      Interestingly, the constitutive overexpression of the DNA-binding domain of rWIN
      also down-regulated transferrin promoter activity. Analysis of the transferrin
      promoter with various deletion mutations suggested that rWIN acts at an upstream
      gene of the transferrin promoter. The results indicate that a transient up
      regulation of rWIN in part mediates the ability of FSH to activate the
      transferrin promoter, which can be inhibited with a rWIN antisense
      oligonucleotide or constitutive expression of the rWIN DNA-binding domain. The
      current study demonstrates that rWIN acts as an early event gene for FSH actions
      on Sertoli cells and that rWIN appears to have a role in the regulation of
      Sertoli cell differentiated functions.

PMID- 10919261
TI  - Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other
      lipid peroxidation products.
AB  - Lipid peroxidation due to oxidative stress is accelerated under hyperglycemic
      conditions such as diabetes mellitus. The effect of 4-hydroxy-2-nonenal (HNE) and
      other lipid peroxidation products on the ability of isolated rat pancreatic
      islets to secrete insulin was examined in this study. HNE concentration- and time
      dependently deteriorated glucose-induced insulin secretion: insulin secretion was
      decreased by 50% when measured after incubation of islets with 100 microM HNE for
      1 h. Other lipid peroxidation products, e.g. 2-hexenal and 2-butenal, also
      inhibited glucose-induced insulin secretion. HNE at 100 microM lowered alpha
      ketoisocaproate-induced insulin secretion, whereas leucine-induced insulin
      secretion was stimulated. Insulin secretion induced by 10 mM glyceraldehyde was
      slightly decreased by HNE. On the other hand, HNE severely decreased insulin
      secretion induced by 10 mM glyceraldehyde and 2.8 mM glucose. Glucose utilization
      and glucose oxidation were significantly lowered in islets treated with HNE. The
      amounts of fructose 1,6-bisphosphate and dihydroxyacetone phosphate in islets
      were decreased by treatment with HNE, whereas the amount of fructose 6-phosphate
      was increased. Our study indicates that HNE and other lipid peroxidation products
      impair insulin secretion induced by glucose probably through affecting both the
      glycolytic pathway and the citric acid cycle.

PMID- 10919262
TI  - Protein kinase Ctheta expression is increased upon differentiation of human
      skeletal muscle cells: dysregulation in type 2 diabetic patients and a possible
      role for protein kinase Ctheta in insulin-stimulated glycogen synthase activity.
AB  - Protein kinase C (PKCtheta) is a key enzyme in regulating a variety of cellular
      functions, including growth and differentiation. PKCtheta is the most abundant
      PKC isoform expressed in skeletal muscle; however, its role in differentiation
      and metabolism is not clear. We examined the effect of muscle cell
      differentiation on PKCtheta expression in human skeletal muscle cells from normal
      and type 2 diabetic subjects. Low levels of PKCtheta messenger RNA (mRNA) and
      protein were detected in human myoblasts from both types of subjects. Upon
      differentiation into myotubes, PKCtheta mRNA and protein were increased 12-fold
      in myotubes from normal subjects. In human skeletal muscle cells obtained from
      type 2 diabetic subjects, increases in PKCtheta mRNA and protein were not
      observed upon differentiation into myotubes although expression of other markers
      of differentiation and fusion increased. Cells from type 2 diabetic subjects also
      exhibited decreased insulin-stimulated glycogen synthase activity. To determine
      whether the up-regulation of PKCtheta was important for the metabolic actions of
      insulin, PKCtheta was overexpressed in L6 rat skeletal muscle cells. Increased
      expression of PKCtheta occurred with differentiation of skeletal muscle myoblasts
      to myotubes. Glycogen synthase activity was further increased in L6 myotubes
      stably transfected with the complementary DNA for PKCtheta. The decreased
      expression of PKCtheta found in cells from type 2 diabetic subjects may be linked
      to insulin resistance and decreased glycogen synthase activity.

PMID- 10919263
TI  - Spermiation failure is a major contributor to early spermatogenic suppression
      caused by hormone withdrawal in adult rats.
AB  - Spermiation is the process by which mature sperm are released from the Sertoli
      cell into the lumen of the seminiferous tubule. Previous studies have shown that
      FSH and LH/testosterone suppression causes a significant increase in the
      degeneration of mature elongated spermatids. The purpose of this study was to
      investigate the extent to which spermiation failure contributes to the overall
      failure of spermatogenesis during hormone suppression. We used in vivo models to
      selectively suppress either FSH, by passive immunization, and or testosterone, by
      administration of SILASTIC brand (Dow Corning) testosterone and estradiol
      implants to suppress LH and testicular testosterone production. Stereological
      quantitation of the number of step 17-18 spermatids before spermiation and the
      number of step 19 spermatids retained within the epithelium after spermiation
      showed that 2% of spermatids failed to spermiate in control animals, and 11% and
      14% of spermatids failed to spermiate after 1 week of FSH inhibition or
      testosterone suppression, respectively. After 1 week of combined FSH and
      testosterone withdrawal, 50% of the spermatids in the testis failed to be
      released. A time course of testosterone suppression showed that after 4-5 weeks
      over 90% of spermatids failed to spermiate. We conclude that spermiation is
      highly sensitive to hormone suppression, with T and FSH acting synergistically to
      support spermiation, and that spermiation inhibition is a potential target for
      contraception.

PMID- 10919264
TI  - Androgen formation and metabolism in the pulmonary epithelial cell line A549:
      expression of 17beta-hydroxysteroid dehydrogenase type 5 and 3alpha
      hydroxysteroid dehydrogenase type 3.
AB  - Surfactant synthesis within developing fetal lung type II cells is affected by
      testosterone and 5alpha-dihydrotestosterone (5alpha-DHT). The pulmonary
      epithelial cell line A549, isolated from a human lung carcinoma, like normal lung
      type II cell, produces disaturated phosphatidylcholines and has been widely used
      for studying the regulation of surfactant production. Androgen receptor has been
      detected in A549 cells; however, the capacity of these cells for androgen
      synthesis and metabolism has not been investigated at molecular level. This study
      was undertaken to identify the steroidogenic enzymes involved in the formation
      and metabolism of androgens from adrenal C19 steroid precursors in A549 cells.
      When cultured in the presence of normal FCS, A549 intact cells converted DHEA to
      androstenediol, androstenedione principally to testosterone, and 5alpha-DHT to
      5alpha-androstane 3alpha,17beta-diol. High levels of 17beta-hydroxysteroid
      dehydrogenase (HSD) and 3alpha-HSD activities were detected in both cytosol and
      microsomes isolated from homogenates. Analysis of A549 RNA indicated the presence
      of 17beta-HSD type 4 and type 5, and of 3alpha-HSD type 3 messenger RNAs. Very
      low levels of 3beta-HSD type 1 and 5alpha-reductase type 1 messenger RNAs and
      activities were detected. With regard to active androgen formation, there was
      little or no capacity for the conversion of DHEA to 5alpha-DHT. In contrast,
      androstenedione was rapidly transformed to testosterone. The pattern of steroid
      metabolism was not affected by the use of charcoal-stripped FCS or by the
      synthetic glucocorticoid dexamethasone. Together, our findings show that A549
      cells express a pattern of steroid metabolism in which 17beta-HSD type 5 and
      3alpha-HSD type 3 are the predominant enzymes. The level of androgens is
      regulated at the level of catalysis in intact cells such that the intracellular
      level of testosterone is stabilized, whereas 5alpha-DHT is rapidly inactivated by
      reduction to 3alpha,17beta-diol. This pattern of androgen metabolism has
      implications for the relative importance of testosterone and 5alpha-DHT in normal
      lung development and surfactant production.

PMID- 10919266
TI  - The 3'-untranslated region of the human estrogen receptor alpha gene mediates
      rapid messenger ribonucleic acid turnover.
AB  - Human estrogen receptor-alpha messenger RNA (hERalpha mRNA) has a relatively
      short half-life, which was determined to be approximately 5 h in MCF-7 cell line
      after actinomycin D treatment. The 3'-untranslated region (3'UTR) of hERalpha
      mRNA was previously shown to completely down-regulate chloramphenicol
      acetyltransferase activity when present at the 3'-end of chloramphenicol
      acetyltransferase transcripts, suggesting a destabilizing function of the
      hERalpha 3'UTR sequence. Chimeric genes composed of a serum-inducible Fos
      promoter, GH-coding sequences, and different segments of the hERalpha
      complementary DNA 3'UTR sequence were used to confirm this hypothesis and to
      localize the RNA region responsible for the destabilizing effect. The presence of
      the complete hERalpha 3'UTR reduced the half-life of the reporter mRNA from more
      than 24 to 3 h. When the hERalpha 3'UTR was subdivided into four fragments (UTR1
      4), one fragment, UTR2, retained the most ability to down-regulate the reporter
      mRNA (t1/2 = 4 h). A stretch of four AUUUA motifs within UTR2 was shown not to
      mediate mRNA destabilization. In contrast, further subdivision of the UTR2 into
      three parts (UTR2a-c) resulted in the loss of the destabilizing activity.
      Finally, recombination of two UTR2 subfragments (UTR2a and -b) partially restored
      this function, indicating a cooperative role among the three UTR2a-c subfragments
      in the process that leads to destabilization of the hERalpha transcript.

PMID- 10919265
TI  - Characterization of neuropeptide Y-mediated corticotropin-releasing factor
      synthesis and release from human placental trophoblasts.
AB  - Neuropeptide Y (NPY) is a CRF secretagogue for human placental cells in culture.
      We have studied the involvement of intracellular calcium and calcium-dependent
      signaling in the NPY-induced CRF release in trophoblastic cells. The incubation
      of trophoblasts with NPY for 3 and 8 h led to a dose-dependent increase in CRF
      secretion. Also, NPY stimulated synthesis of this peptide hormone upon an 8-h
      incubation period. BIBP3226, a selective Y1 receptor antagonist, and pertussis
      toxin (PTX) eliminated these effects. NPY-stimulated CRF secretion was mostly
      prevented by loading cells with BAPTA-AM, suggesting that elevation of
      intracellular calcium is responsible for the increase of CRF secretion. However,
      this calcium chelator had no effect on CRF synthesis. Furthermore, U-73122, a
      phospholipase C-betas (PLC) inhibitor or xestospongin C, an inositol triphosphate
      receptor (InsP3-R) blocker, have partially prevented the effect of NPY on CRF
      synthesis and secretion. Therefore, the increase in CRF synthesis and secretion
      rely in part on the release of calcium from intracellular store. Interestingly,
      SKF 96365, an inhibitor of store operated calcium (SOC) influx, also partially
      blocked the NPY stimulatory effect on CRF release but not its synthesis,
      suggesting that calcium influx is also involved in this stimulation. In the
      syncytiotrophoblast, known to possess a NPY-activated protein kinase C (PKCs)
      activity, NPY also stimulated calcium calmodulin kinase II (CaMKII) and
      extracellular regulated kinase (ERK1/2) activities. In the present study, we
      observed that bisindolylmaleimide (BIM), a nonspecific PKCs inhibitor partially
      prevented the NPY-induced CRF release. On the other hand, autocamtide-2 related
      inhibitory peptide (AIP), a CaMKII inhibitor, prevented most of the stimulatory
      effect of NPY on both CRF synthesis and release. Go6976, an inhibitor of the
      conventional and mu PKCs and PD 098059, an inhibitor of the ERK cascade, had no
      effect on neither CRF synthesis nor release. Altogether, these results support a
      Y1 receptor-mediated PTX-sensitive induction on CRF synthesis and release by NPY
      from human placental trophoblasts. The stimulation of CRF synthesis by NPY seems
      to depend mainly on a PLC-beta to InsP3-R axis and on CaMKII activity. Also, the
      release of CRF depends on the PLC-beta to InsP3-R axis and CaMKII activity but
      also entails the participation of a calcium-independent PKCs.

PMID- 10919268
TI  - Interleukin-1beta regulates phospholipase D-1 expression in rat pancreatic beta
      cells.
AB  - The cytokine interleukin (IL)-1beta induces a biphasic effect in rat pancreatic
      islets, with an early and transitory stimulation of insulin release followed by
      progressive functional suppression. To clarify the mechanisms involved in these
      effects, we have recently performed a differential display of messenger RNA
      (mRNA) by RT-PCR (DDRT-PCR) on rat beta-cells exposed for 6 or 24 h to IL-1beta.
      Among the different IL-1beta-induced genes, there was an early and transient
      increase in phospholipase D-1 (PLD1) expression. PLD1 can induce phosphatidic
      acid formation and subsequent activation of protein kinase C, a process which
      stimulates insulin release. In the present study, we characterized the regulation
      of PLD isoforms by IL-1beta in pancreatic beta-cells. By using different
      combinations of primers and RT-PCR, we observed that IL-1beta induces an early
      increase (2 and 6 h) in the expression of both alternatively spliced isoforms of
      PLD1 (PLD1alpha and 1b). Prolonged exposure to IL-1beta (12 and 24 h) caused a
      decrease of PLD1a mRNA expression compared with control beta-cells, and lead to a
      return of PLD1b mRNA to basal level. NG-methyl-L-arginine (LMA), a blocker of the
      inducible form of nitric oxide synthase (iNOS), prevented this late inhibitory
      effect of IL-1beta, suggesting that IL-1beta-induced decrease in PLD1a expression
      is NO-mediated. IL-1beta induced an early (2-6 h) and sustained (16-24 h)
      increase in PLD1a mRNA expression in insulin-producing RINm5F cells. This was
      paralleled by a cytokine-induced increase in PLD1 protein expression and enzyme
      activity. RINm5F cells, but not primary beta-cells, expressed PLD2, and the
      expression of this gene was not affected by IL-1beta. In conclusion, we have
      shown that the cytokine IL-1beta regulates PLD1 expression in primary and clonal
      beta-cells. The early induction of PLD1 probably contributes to the early
      stimulatory effects of IL-1beta on islet insulin release.

PMID- 10919267
TI  - Laminin inhibits estrogen action in human breast cancer cells.
AB  - Breast tumors that lack estrogen responsiveness have a poor prognosis. Despite
      the critical importance to breast cancer treatment, little is known about the
      loss of estrogen responsiveness and the development of antiestrogen resistance.
      We have examined the regulation of estrogen-induced proliferation, estrogen
      regulation of progesterone receptor (PR) expression, and estrogen signaling
      pathways in estrogen receptor (ER) positive (MCF-7 and T47D) breast cancer cell
      lines by specific extracellular matrix proteins (ECM) under serum-free
      conditions. Estrogen, supplemented with submaximal concentrations of insulin-like
      growth factor I (IGF-I) and epidermal growth factor (EGF), stimulated DNA
      synthesis of MCF-7 cells 7- to 10-fold and T47D cells 2-fold on collagen I or
      fibronectin. However, estrogen-induced proliferation was greatly reduced on
      laminin. In contrast, IGF-I or EGF, alone, stimulated proliferation of MCF-7 and
      T47D cells on all ECM. Thus, ER+ breast cancer cells were not refractory to
      mitogens when cultured on laminin. Similarly, estrogen induction of PR occurred
      on fibronectin or collagen I, but not on laminin. While ER content was similar on
      all ECM, estrogen stimulation of estrogen response element (ERE)-luciferase
      activity was significantly lower in MCF-7 cells cultured on laminin. Therefore,
      changes in ECM composition that occur in breast cancer may alter estrogen
      responsiveness and the effectiveness of antiestrogen therapies in ER+ breast
      cancer cells.

PMID- 10919269
TI  - Identification of a hormone-responsive promoter immediately upstream of exon 1c
      in the human vitamin D receptor gene.
AB  - To gain insight into the molecular regulation of the human vitamin D3 receptor
      (hVDR), we have cloned and sequenced the 5' flanking region of exon 1c and
      examined promoter activity of this region in breast cancer cells. Sequence
      analysis of the first 1300 bp upstream of exon 1c reveals several characteristics
      of a class II promoter, including GC-rich regions and the presence of a TATA box
      at -29 bp. Putative transcription factor binding sites identified in this
      potential hVDR promoter include AP-2, Sp-1, and glucocorticoid response elements.
      No consensus vitamin D3 (VDRE) or estrogen (ERE) responsive elements were
      identified in the promoter sequence. Primer extension analysis performed with a
      primer specific for exon 1c confirms that transcription initiated in the 5'
      flanking region of exon 1c occurs in MCF-7 cells. Transient transfection of MCF-7
      cells with this putative promoter region cloned into the pRLnull luciferase
      reporter vector generates significant reporter gene activity that is enhanced by
      treatment with forskolin, retinoic acid, and 17beta-estradiol. The enhancement of
      exon 1c promoter activity by 17beta-estradiol is blocked by the selective
      estrogen response modifier (SERM) tamoxifen and is not observed in estrogen
      receptor-negative breast cancer cells. In summary, we have cloned and
      characterized a TATA containing promoter upstream of exon 1c of the hVDR and
      provide evidence that this region represents a hormonally regulated hVDR
      promoter.

PMID- 10919271
TI  - Effect of growth hormone and insulin-like growth factor I (IGF-I) on the
      expression of IGF-I messenger ribonucleic acid and peptide in rat tibial growth
      plate and articular chondrocytes in vivo.
AB  - Conflicting data exist as to whether insulin-like growth factor I (IGF-I)
      messenger RNA (mRNA) and peptide are expressed within chondrocytes. This question
      is pertinent to the mode of GH action on longitudinal bone growth. We have,
      therefore, investigated this issue in normal rats and in hypophysectomized rats
      treated for 24 h with GH or IGF-I using in situ hybridization and
      immunohistochemistry. Serum IGF-I, body weight, and tibial growth plate, but not
      articular cartilage, height increased with both treatments. Both IGF-I mRNA and
      IGF-I immunoreactivity occurred in all chondrocyte layers of growth plate and
      articular cartilage. The percentage of cells with IGF-I mRNA correlated well with
      IGF-I immunoreactivity under all experimental conditions. In normal rats, IGF-I
      expression was highest in the upper hypertrophic zone in growth plate (68-71%)
      and articular cartilage (32-34%). Hypophysectomy, GH, or IGF-I did not
      significantly affect this percentage. In the stem cell and proliferative and
      lower hypertrophic zones of growth plate, hypophysectomy dramatically reduced the
      percentage of labeled chondrocytes, and GH restored it. IGF-I increased IGF-I
      mRNA and immunoreactivity only in the proliferative zone. In articular cartilage,
      both remained unchanged under all experimental conditions. Together with our
      previous finding that GH infusion of hypophysectomized rats enhances chondrocyte
      maturation at all differentiation stages, the present results are compatible with
      the idea that IGF-I produced by all chondrocyte layers under the influence of GH
      mediates chondrocyte maturation and thus longitudinal bone growth in an
      autocrine/paracrine manner.

PMID- 10919270
TI  - Estradiol stimulation of c-fos and c-jun expressions and activator protein-1
      deoxyribonucleic acid binding activity in rat white adipocyte.
AB  - In order to elucidate the molecular mechanisms whereby ovarian hormones, and
      particularly estrogens, modulate fat cell metabolism, we investigated the effects
      of estradiol administration on c-fos and c-jun expressions in fat cells from
      ovariectomized (OVX) rats. Estradiol treatment resulted in a rapid increase in c
      fos and c-jun messenger RNA (mRNA) and protein levels (about 2-fold). These
      effects of estradiol on c-fos and c-jun mRNAs were blocked by actinomycin D but
      not by cycloheximide treatment, suggesting that estradiol modulates c-fos and c
      jun transcription. Moreover, the estradiol-induction of both transcripts was
      partially suppressed by the estrogen-receptor antagonist ICI 182,780. In
      contrast, progesterone administration did not affect c-fos and c-jun mRNA levels
      indicating a hormonal specificity of estrogen action. However, an antagonism of
      estradiol-induction of both genes was observed after progesterone treatment. In
      addition, the estradiol-induced changes in c-fos and c-jun mRNA expressions could
      not be observed in castrated males suggesting a gender-specific effect of
      estradiol. Finally, in OVX rats, estradiol treatment stimulated the specific AP-1
      DNA binding activity (about 5-fold) in adipocyte nuclear extracts as assessed by
      electrophoretic mobility shift assays. These results suggest that some of the
      estrogen effects in fat cells from female rats are mediated through induction of
      the AP-1 complex expression and consequently through modulation of the AP-1
      dependent gene expression in adipocytes.

PMID- 10919272
TI  - Cocaine-amphetamine-regulated transcript (CART) acts in the central nervous
      system to inhibit gastric acid secretion via brain corticotropin-releasing factor
      system.
AB  - Recent study has indicated that cocaine-amphetamine-regulated transcript (CART)
      is an anorectic chemical in the brain. In the present study, we examined the
      hypothesis that CART may act in the central nervous system to alter gastric
      function. Food consumption, gastric acid secretion, and gastric emptying were
      measured after injection of CART into the cerebrospinal fluid in 24-h fasted
      Sprague Dawley rats. Central injection of CART inhibited food intake, gastric
      acid secretion, and gastric emptying. In contrast, ip injection of CART failed to
      inhibit gastric acid secretion and gastric emptying, suggesting that CART acts in
      the brain to suppress gastric acid secretion and gastric emptying. In the
      vagotomized animals, centrally administered CART did inhibit pentagastrin
      stimulated gastric acid secretion. The CART-induced acid inhibition was also
      observed in rats treated with indomethacin, a cyclooxygenase inhibitor. In
      contrast, pretreatment with central administration of a CRF receptor antagonist,
      alpha-helical CRF9-41, completely blocked the central CART-induced inhibition of
      gastric acid secretion. All these results suggest that CART acts in the brain to
      inhibit gastric function via brain CRF system. The vagal pathway and the
      prostaglandin system are not involved in the acid inhibition.

PMID- 10919273
TI  - Estrogenic induction of spermatogenesis in the hypogonadal mouse.
AB  - Abnormal sperm production and reduced fertility have been reported in transgenic
      male mice lacking the alpha-subtype of the estrogen receptor (ER)alpha or
      aromatase. The aim of this study was to investigate the role of estrogen in male
      reproductive function, by determining the effect of estradiol on testicular
      function in hypogonadal (hpg) mice congenitally lacking gonadotropin; and thus,
      sex steroid production. hpg mice were treated, at 2-3 months of age, with slow
      release estradiol implants, which achieved circulating estradiol concentrations
      of approximately 40 pg/ml. Treatment for 35 days reliably induced a 4- to 6-fold
      increase in testicular weight, compared with the vestigial testes in the
      untreated or cholesterol-treated controls. The degree of testicular growth after
      35 days was similar to that in hpg mice receiving an intrahypothalamic graft of
      preoptic area tissue taken from neonatal mice on the day of birth, a procedure
      known to induce testicular development in hpg mice by activation of the pituitary
      gland. Histological analysis revealed that the testes contained elongated
      spermatids after 35 days of estradiol treatment, whereas germ cell development
      never progressed beyond the pachytene stage in control hpg mice. Treatment for 70
      days induced full qualitatively normal spermatogenesis in hpg mice. Testis weight
      increased 5-fold, reflecting a 5-fold increase in total seminiferous tubule
      volume and a 4- to 5-fold increase in the total volume of the seminiferous
      epithelium. In all experiments, spermatogenesis proceeded in the absence of
      measurable androgen concentrations, but circulating FSH concentrations were
      slightly (but significantly) elevated, relative to cholesterol-treated control
      hpg mice. This stimulatory action of estradiol on FSH secretion was unexpected,
      particularly because identical estradiol treatments significantly decreased serum
      FSH levels in wild-type littermates. These results indicate that estrogens may
      play a role in spermatogenesis, via stimulatory effects on FSH secretion. An
      alternative or complementary explanation, given the recent identification of
      estrogen receptors (ERalpha and ERbeta) and aromatase within various cell types
      in the testis, is that estrogens exert paracrine actions within the testis to
      promote spermatogenesis. The identification of effects of estradiol on testicular
      function provides a conceptual basis to reexamine the speculative link between
      increased exposure to environmental estrogens and reduced fertility in man.

PMID- 10919275
TI  - Antigen-presenting cells in the female reproductive tract: influence of estradiol
      on antigen presentation by vaginal cells.
AB  - The objective of the present study was to define the afferent arm of the mucosal
      immune system in the lower female reproductive tract. We report here that antigen
      presentation by vaginal cells is under hormonal control. When vaginal cells from
      ovariectomized rats treated with estradiol (0.01-10 microg) were incubated with
      ovalbumin-specific T cells and ovalbumin, a dose-dependent inhibition of antigen
      presentation was measured. In time course studies, estradiol given to
      ovariectomized rats inhibited vaginal cell antigen presentation within 24 h after
      a single injection, relative to that seen in saline controls. To determine
      whether changes in antigen presentation were attributable to the effect of
      estradiol on the number of antigen-presenting cells (APCs) in the vagina, tissues
      were analyzed by immunohistochemistry. Our findings indicate that estradiol
      inhibited antigen presentation without affecting the number of major
      histocompatibility complex class II positive cells and at a time when
      macrophage/dendritic cells/granulocytes in the vagina increase in response to
      estradiol treatment. Antibody neutralization studies indicated that antigen
      presentation by vaginal cells from ovariectomized rats is mediated through class
      II and involves the expression of transmembrane proteins B7.1 and B7.2. In other
      studies, vaginal APCs interact with thymus APCs to synergistically enhance
      antigen presentation under conditions in which vaginal antigen presentation is
      inhibited by estradiol. Analysis of conditioned media indicates that enhancement
      of thymus antigen presentation involves the release of a soluble factor(s) into
      the culture media of vaginal cells. When spleen cells were cocultured with
      vaginal cells from saline-treated rats, proliferation increased in the presence
      of concanavalin A and/or phytohemagglutinin and decreased with
      lipopolysaccharide, relative to spleen cells and mitogen alone. In contrast, when
      incubated with vaginal cells from estradiol-treated rats, spleen cell
      proliferation was not affected with concanavalin but was inhibited with
      phytohemagglutinin and lipopolysaccharide. These studies demonstrate that
      estradiol regulates antigen presentation by vaginal cells and that vaginal cells,
      in turn, influence antigen presentation, as well as B and T cell proliferation.

PMID- 10919274
TI  - Corticotropin-releasing hormone type I receptor messenger ribonucleic acid and
      protein levels in the ovine fetal pituitary: ontogeny and effect of chronic
      cortisol administration.
AB  - In sheep, the ACTH secretory response to CRH in vivo or in vitro changes as a
      function of development, with peak responses occurring several weeks before term
      (145 days of gestation). CRH-stimulated ACTH secretion is mediated via the G
      protein-coupled CRH type I (CRH R1) receptor. We used a quantitative ribonuclease
      protection assay and Western immunoblotting to determine messenger RNA (mRNA) and
      protein levels of the CRH R1 receptor in immature and mature fetuses and adults.
      In addition, we precociously elevated fetal plasma cortisol levels to determine
      whether the fetal CRH R1 receptor is sensitive to increases in plasma cortisol.
      CRH R1 receptor mRNA levels decreased markedly throughout gestation and into the
      transition to adult life (immature fetus, 1.24+/-0.17; mature fetus, 0.75+/-0.13;
      adult, 0.18+/-0.093 pg/microg total anterior pituitary RNA). Also, continuous
      cortisol infusion in immature fetuses significantly decreased CRH R1 mRNA levels
      by 41%. Similar decreases were noted in protein levels. Thus, the decreased ACTH
      response to CRH stimulation during late gestation may be related to decreased CRH
      R1 receptor expression. In addition, plasma cortisol levels may influence
      corticotroph responsiveness to CRH by decreasing CRH R1 receptor expression.

PMID- 10919276
TI  - Insulin-like growth factor I disparately regulates prolactin and growth hormone
      synthesis and secretion: studies using the teleost pituitary model.
AB  - Although insulin-like growth factor I (IGF-I)'s inhibition of GH release is well
      documented, little is known of its control of GH synthesis at the
      posttranscriptional level. The manner by which IGF-I alters PRL synthesis and
      secretion is also unclear. This study was undertaken to examine the role IGF-I
      plays in regulating in vitro PRL and GH synthesis and release using the teleost
      pituitary model system. This model allows for isolation of nearly homogenous
      populations of distinct pituitary cell types that can be cultured in a completely
      defined, hormone-free medium. Tissues containing PRL cells and those consisting
      of GH cells were dissected from pituitaries of hybrid striped bass and exposed to
      varying concentrations of IGF-I, IGF-II, and insulin for 18-20 h. Exposure to
      graded doses of IGF-I markedly stimulated fractional, total, and newly
      synthesized PRL release in a dose-dependent fashion (ED50 for fractional release,
      35 ng/ml or 4.6 nM; P < 0.0001). IGF-II and insulin also increased PRL release,
      but only at 10-fold higher concentrations than the lowest effective IGF-I dose.
      The total PRL content in the incubations and PRL synthesis, as measured by
      [35S]methionine incorporation, were not altered by IGF-I. By contrast, IGF-I
      potently reduced GH release (ED50, 29 ng/ml or 3.8 nM; P < 0.0001) and synthesis.
      Both 100 and 1000 ng/ml IGF-I decreased newly synthesized GH and total GH content
      (P < 0.001). Insulin and IGF-II mimicked IGF's action in attenuating GH release,
      but only at 10- to 11-fold higher concentrations. Taken together, these findings
      clearly indicate that IGF-I disparately regulates PRL and GH synthesis and
      secretion. We show that the effects of IGF-I on pituitary hormone release occur
      in a variety of species, suggesting that its actions are well conserved. The
      inhibition of GH release and synthesis by IGF-I probably reflects a negative
      feedback loop for maintaining tight control over GH cell function. These findings
      further indicate that IGF-I is a potent and specific secretagogue of PRL release
      in vertebrates.

PMID- 10919277
TI  - Sp1 and SF-1 interact and cooperate in the regulation of human steroidogenic
      acute regulatory protein gene expression.
AB  - Steroidogenic acute regulatory (StAR) protein plays a critical role in the
      movement of cholesterol from the outer to the inner mitochondrial membrane.
      Steroidogenic factor 1 (SF-1) controls basal and cAMP-stimulated transcription of
      the StAR gene. The 1.3-kb StAR promoter has three SF-1 binding sites, and two
      consensus transcription factor Spl binding sequences near the two most distal SF
      1 binding sites. Spl mediates cAMP-dependent transcription of steroidogenic P450
      enzyme genes, raising the possibility of Sp1 involvement in cAMP regulation of
      the StAR gene. However, the mechanism of Spl-mediated, cAMP-stimulated
      responsiveness is not known. In this study, we elucidated the roles of Sp1 and SF
      1 in the regulation of the human StAR gene promoter. We found that there was
      negligible promoter activity in a pGL2 StAR construct (-235 to +39) in which Spl
      and SF-1 binding sites were mutated in Y-1 adrenal tumor cells. An Sp1 binding
      site mutation (pGL2Sp1M) did not support promoter activity, suggesting that Spl
      cooperates with SF-1 in regulating StAR promoter function. In gel shift assays,
      the SF-1 binding site formed a complex with an SF-1-GST fusion protein and Spl.
      Coimmunoprecipitation cross-linking experiments indicated that SF-1 physically
      interacts with Sp1 in vitro. Finally, a mammalian two-hybrid system was employed
      to demonstrate that Spl and SF-1 associate in vivo. In conclusion, our data
      indicate that Spl and SF-1 physically interact and cooperate in the regulation of
      human StAR promoter activity.

PMID- 10919278
TI  - Dexamethasone suppresses tumor necrosis factor-alpha-induced apoptosis in
      osteoblasts: possible role for ceramide.
AB  - Ceramide has been proposed as a second messenger molecule implicated in a variety
      of biological processes, including apoptosis. Recently, it has been reported that
      tumor necrosis factor-alpha (TNF-alpha) activates the release of ceramide and
      that ceramide acts as a mediator for the TNF-alpha-induced stimulation of the
      binding affinity of nuclear factor-KB (NF-KB), a ubiquitous transcription factor
      of particular importance in immune and inflammatory responses. In this study we
      demonstrate that dexamethasone, which reduces the production of ceramide,
      significantly inhibits TNF-alpha-induced activation of NF-KB, c-Jun N-terminal
      kinase, also known as stress-activating protein kinase, caspase-3-like cysteine
      protease, redistribution of cytochrome c, and apoptosis in MC3T3E1 osteoblasts.
      Compared with TNF-alpha-induced JNK activation, ceramide elicits a more rapid
      activation of JNK within 30 min. C2-ceramide activates NF-KB and caspase-3 like
      protease to the same degree and with kinetics similar to those of TNF-alpha. This
      study provides evidence that the release of ceramide may be required as a second
      messenger in TNF-alpha-induced apoptosis. These results also suggest a regulatory
      role for dexamethasone in TNF-alpha-induced apoptosis via inhibition of ceramide
      release. Therefore, our in vitro results suggest that therapies targeted at the
      inhibition of ceramide release may abrogate inflammatory processes in TNF-alpha
      related diseases, including rheumatoid arthritis and periodontitis.

PMID- 10919279
TI  - Nuclear factor-kappaB p50 is required for tumor necrosis factor-alpha-induced
      colony-stimulating factor-1 gene expression in osteoblasts.
AB  - Colony-stimulating factor (CSF)-1 is a hematopoietic growth factor that is
      released by osteoblasts and is recognized to play a critical role in bone
      remodeling in vivo and in vitro. We have reported that osteoblasts express CSF-1
      constitutively and that tumor necrosis factor (TNF)-alpha, a potent bone
      resorbing agent, increases CSF-1 gene expression by a transcriptional mechanism.
      In the present study, we report that an NF-kappaB site in the CSF-1 promoter is
      required for TNF-alpha-induced CSF-1 expression in osteoblasts. As determined by
      electrophoretic mobility shift assays, antiserum against the NF-kappaB-binding
      protein, p50, retarded the mobility of the inducible complex, whereas antisera
      against p52, p65, c-Rel, Rel B, IkappaB alpha, IkappaB gamma, and Bcl-3 had no
      effect. To further confirm that p50 is necessary for TNF-alpha-induced CSF-1
      expression in osteoblasts, CSF-1 messenger RNA expression from untreated and TNF
      alpha-treated osteoblasts, prepared from wild-type and p50 knock-out mice, was
      examined by Northern analysis. CSF-1 messenger RNA was increased by TNF treatment
      in wild-type mice but not in NF-kappaB p50 knock-out mice. Our findings support
      the conclusion that the NF-kappaB subunit p50 is critical for TNF-induced CSF-1
      expression in osteoblasts.

PMID- 10919280
TI  - Androgen regulation of signaling pathways in late fetal mouse lung development.
AB  - During lung development there is tension between positive and negative regulators
      of fibroblast-epithelial communication controlling type II cell differentiation.
      A clinical consequence of imbalance of this tension is the increased risk for
      respiratory distress syndrome in male infants. We hypothesized that chronic
      intrauterine androgen exposure alters fetal lung fibroblast maturation by down
      regulating epidermal growth factor receptor (EGF-R) activity and by up-regulating
      transforming growth factor-beta receptor (TGFbeta-R) activity, leading to an
      inhibition of surfactant protein B (SP-B) and -C (SP-C) gene expression in type
      II cells. We treated pregnant mice with dihydrotestosterone (DHT; 2 mg/day) or
      vehicle for 7 days, starting on gestational day 11. On day 18, EGF binding, EGF-R
      phosphorylation, TGFbeta-R binding, and TGFbeta1-induced cell proliferation were
      studied in sex-specific fibroblast cultures. SP-B and -C messenger RNA levels
      were measured in whole lungs. Chronic DHT treatment reduced both EGF binding
      (females to 78+/-8% and males to 65+/-9% of controls) and EGF-induced EGF-R
      phosphorylation. TGFbeta-R binding was increased (females to 173+/-39% and males
      to 280+/-64% of controls), and TGFbeta-induced cell proliferation was increased
      in female cells (231+/-57% of controls). SP-B and -C messenger RNA expression was
      reduced to 55+/-10% and 75+/-4%, respectively. We conclude that chronic DHT
      exposure beginning early in lung development alters the balance of growth factor
      signaling that regulates lung maturation.

PMID- 10919281
TI  - Characterization of hyperpolarization-activated cation currents in mouse anterior
      pituitary, AtT20 D16:16 corticotropes.
AB  - The properties of the hyperpolarization-activated inward cation current (Ih) in
      mouse anterior pituitary, AtT20 D16:16 corticotropes was characterized by whole
      cell patch clamp recording. In response to hyperpolarizing steps a large, slowly
      activating, voltage-dependent inward current was activated with a half maximal
      activation voltage (V0.5) of -96.2+/-3.1 mV with a time constant of 168+/-13 msec
      determined at -140 mV at room temperature. Ih had a reversal potential of -35.5+/
      1.0 mV and -23.3+/-1.4 mV using 5 mM and 25 mM extracellular K+, respectively,
      with a relative permeability ratio for Na+ and K+ of 0.24. The current was
      completely blocked by 2 mM extracellular CsCl and partially blocked by ZD7288
      (100 microM) but was unaffected by TEA (10 mM) or Ba2+ (1 mM). RT-PCR analysis
      revealed robust expression of HCN1, but not HCN2 or HCN3, subunits of
      hyperpolarization-activated cation channels. The endogenous Ih current was weakly
      activated by cAMP but robustly inhibited by the cAMP antagonist, Rp-8-CPT-cAMPS.
      Activation or suppression of protein kinase C activity had no significant effect
      on the Ih current. The data suggest that in AtT20 D16:16 corticotropes Ih is
      tonically regulated by the cAMP-signaling cascade and may serve to limit
      excessive hyperpolarization.

PMID- 10919282
TI  - Endocrine disruptive effects of polychlorinated aromatic hydrocarbons on
      intestinal cholecystokinin in rats.
AB  - The ubiquitous and persistent nature of polychlorinated aromatic hydrocarbons
      (PCAHs) in our environment and the risk of exposure to PCAHs have provoked
      concern over their potential toxicity. In humans, exposure to PCAHs is aimed
      chiefly at epithelial cells residing in the intestinal mucosa, because oral
      intake of contaminated food is a major source of PCAHs. The purpose of this
      study, therefore, was to examine the effects of chronic exposure to various PCAHs
      [i.e. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8
      pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PCB-126), and
      2,2'4,4'5,5'-hexachlorobiphenyl (PCB-153)], given alone or as mixtures, on
      intestinal cholecystokinin (CCK) peptide and messenger RNA levels. We show that
      chronic PCAH treatment significantly lowers intestinal levels of stored CCK
      peptide. Intestinal CCK messenger RNA levels are not affected. In addition,
      3,3',4,4',5-pentachlorobiphenyl treatment increased intestinal insulin-like
      growth factor-binding protein-3 levels in a dose-related manner. Acute 2,3,7,8
      tetrachlorodibenzo-p-dioxin treatment of intestinal CCK cells lowered levels of
      CCK-processing enzymes (i.e. prohormone convertase-1 and -2). Together, these
      data indicate that PCAHs may decrease intestinal levels of stored CCK peptide by
      affecting the intestinal insulin-like growth factor system and CCK processing.

PMID- 10919283
TI  - Dexamethasone inhibits insulin-like growth factor signaling and potentiates
      myoblast apoptosis.
AB  - In the critically ill, glucocorticoids induce myopathy, combining profound
      protein catabolism and mild myotubular death. Insulin-like growth factors (IGFs)
      inhibit muscle catabolism through activation of phosphatidylinositol 3-kinase
      (PI3K). Using rat L6 myoblasts, we show that IGF-I also acts through PI3K to
      inhibit apoptosis induced by hyperosmolar metabolic stress with 300 mM mannitol.
      We find that the glucocorticoid dexamethasone inhibits this antiapoptotic effect
      of IGF-I by impairing PI3K signaling. Dexamethasone induces overexpression of the
      PI3K subunit p85alpha, which, in turn, competes with the complete PI3K
      heterodimer for binding at insulin receptor substrate-1, inhibiting PI3K
      activation. Dexamethasone blocks IGF-I-induced phosphorylation of Akt, a PI3K
      dependent process. Increased cellular p85alpha abundance, induced by either 10
      microM dexamethasone or transient transfection with a plasmid coding for
      p85alpha, significantly inhibits IGF-I rescue from apoptosis induced by mannitol,
      as indicated by both loss of cell viability and increased activity of caspase-3
      by fluorogenic assay. Conversely, constitutively active PI3K inhibits death
      induced by mannitol, even in the presence of dexamethasone. These findings may
      have particular relevance in the pathogenesis of acute steroid myopathy in
      critical illness, in which catabolic glucocorticoid effects combine with acute
      metabolic stressors, including sepsis, fasting, and chemical denervation.

PMID- 10919284
TI  - The distribution of cells containing estrogen receptor-alpha (ERalpha) and ERbeta
      messenger ribonucleic acid in the preoptic area and hypothalamus of the sheep:
      comparison of males and females.
AB  - We have used in situ hybridization to compare the distributions of estrogen
      receptor alpha (ERalpha) and ERbeta messenger RNA (mRNA)-containing cells in the
      preoptic area and hypothalamus of ewes and rams. Perfusion-fixed brain tissue was
      collected from luteal phase ewes and intact rams (n = 4) during the breeding
      season. Matched pairs of sections were hybridized with sheep-specific, 35S
      labeled riboprobes, and semiquantitative image analysis was performed on emulsion
      dipped slides. A number of sex differences were observed, with females having a
      greater density of labeled cells than males (P < 0.001) and a greater number of
      silver grains per cell (P < 0.01) in the ventromedial nucleus for both ER
      subtypes. In addition, in the retrochiasmatic area, males had a greater (P <
      0.05) cell density for ERalpha mRNA-containing cells than females, whereas in the
      paraventricular nucleus, females had a greater density (P < 0.05) of ERalpha mRNA
      containing cells than males. There was a trend (P = 0.068) in the arcuate nucleus
      for males to have a greater number of silver grains per cell labeled for ERalpha
      mRNA. In both sexes, there was considerable overlap in the distributions of
      ERalpha and ERbeta mRNA-containing cells, but the density of labeled cells within
      each nucleus differed in a number of instances. Nuclei that contained a higher (P
      < 0.001) density of ERalpha than ERbeta mRNA-containing cells included the
      preoptic area, bed nucleus of the stria terminalis, and ventromedial nucleus,
      whereas the subfornical organ (P < 0.001), paraventricular nucleus (males only, P
      < 0.05), and retrochiasmatic nucleus (females only, P < 0.05) had a greater
      density of ERalpha than ERbeta mRNA-containing cells. The anterior hypothalamic
      area and supraoptic nucleus had similar densities of cells containing both ER
      subtypes. The lateral septum and arcuate nucleus contained only ERalpha, whereas
      only ERbeta mRNA-containing cells were seen in the zona incerta. The sex
      differences in the populations of ER mRNA-containing cells in the ventromedial
      and arcuate nuclei may explain in part the sex differences in the neuroendocrine
      and behavioral responses to localized estrogen treatment in these nuclei. Within
      sexes, the differences between the distributions of ERalpha and ERbeta mRNA
      containing cells may reflect differential regulation of the actions of estrogen
      in the sheep hypothalamus. Low levels of ERbeta mRNA in the preoptic area and
      ventromedial and arcuate nuclei, regions known to be important for the regulation
      of reproduction, suggest that ERbeta may not be involved in these functions.

PMID- 10919285
TI  - Tissue-specific expression of a rat renin transcript lacking the coding sequence
      for the prefragment and its stimulation by myocardial infarction.
AB  - An alternative transcript of the rat renin gene was recently characterized in the
      adrenal gland, in addition to the known messenger RNA (mRNA) coding for
      preprorenin. In the alternative transcript, exon 1 is replaced by exon 1A, a
      domain originating in intron 1. The reading frame of this mRNA, termed exon 1A
      renin transcript, codes for a truncated prorenin that presumably remains
      intracellular, in contrast to preprorenin, which is targeted to the secretory
      pathway by its prefragment. We here demonstrate the tissue-specific regulation of
      expression of both transcripts by RT and PCR. In many tissues both transcripts
      are present, for example in the adrenal gland, spleen, liver, and hypothalamus.
      In some organs, however, only one of the renin mRNAs is found. In the kidney only
      the full-length mRNA coding for preprorenin is detected. In the heart exclusively
      the exon 1A-mRNA is expressed, but not the preprorenin transcript. After
      myocardial infarction, which is known to activate the intracardiac renin
      angiotensin system, expression of exon 1A-renin mRNA in the left ventricle was
      stimulated about 4-fold, compared with that in sham-operated animals, whereas no
      mRNA corresponding to preprorenin was detectable. These findings may have
      implications for the current concepts of local extrarenal renin-angiotensin
      systems, as they provide the molecular basis for a possible intracellular
      function of renin and exclude a role for locally produced secretory renin in the
      heart.

PMID- 10919286
TI  - Platelet-derived growth factor-BB stimulates hypertrophy of peritubular smooth
      muscle cells from rat testis in primary cultures.
AB  - The tunica propria of seminiferous tubules contains a particular type of smooth
      muscle cell (myoid cells) arranged in a contractile epithelioid layer that is
      responsible for sperm and tubular fluid flow. Unlike other types of smooth muscle
      (SM) cells, highly purified populations of peritubular smooth muscle cells (PSMC)
      survive and maintain their contractile phenotype in primary cultures in
      controlled conditions. We used this culture model to investigate the response of
      the SM contractile phenotype to prolonged exposure to platelet-derived growth
      factor (PDGF), one of the main factors involved in vascular SM pathologies. We
      observed that 4-day continuous exposure of PSMC to PDGF-BB at nanomolar
      concentrations in plain medium enhances contractile phenotype traits and induces
      cell hypertrophy without inducing proliferation. In Northern and Western blotting
      experiments, SM-alpha-actin transcript and protein were found to be markedly
      increased in the PDGF-BB-treated samples, which is in line with the formation of
      conspicuous SM-alpha-actin-containing stress fibers. Moreover, binding sites for
      endothelin-1 were increased, and the calcium response to the contractile agonist,
      determined in single fura-2-loaded cells, was enhanced. In response to PDGF-BB,
      the cells underwent immediate, transient contraction, as seen in a scanning
      electron microscope, followed by a gradual increase in size, as evaluated by
      cytofluorometry, and enhancement of protein synthesis. The observed pattern of
      response to PDGF-BB was not accompanied by cell proliferation, as assessed by
      [3H]thymidine incorporation and direct cell counts. Unlike other SM cell types,
      in which proliferation and loss of contractile traits are induced by PDGF,
      chronic treatment of PSMC with this growth factor results in hypertrophy rather
      than hyperplasia.

PMID- 10919287
TI  - Induction of mammary gland development in estrogen receptor-alpha knockout mice.
AB  - Mammary glands from the estrogen receptor-a knockout (alphaERKO) mouse do not
      undergo ductal morphogenesis or alveolar development. Disrupted ERalpha signaling
      may result in reduced estrogen-responsive gene products in the mammary gland or
      reduced mammotropic hormones that contribute to the alphaERKO mammary phenotype.
      We report that circulating PRL is reduced in the female alphaERKO mouse.
      Implantation of an age-matched, heterozygous ERalpha pituitary isograft under the
      renal capsule of 25-day-old or 12-week-old alphaERKO mice increased circulating
      PRL and progesterone levels, and induced mammary gland development. Grafted
      alphaERKO mice also possessed hypertrophied corpora lutea demonstrating that PRL
      is luteotropic in the alphaERKO ovary. By contrast, ovariectomy at the time of
      pituitary grafting prevented mammary gland development in alphaERKO mice despite
      elevated PRL levels. Hormone replacement using pellet implants demonstrated that
      pharmacological doses of estradiol induced limited mammary ductal elongation, and
      estradiol in combination with progesterone stimulated lobuloalveolar development.
      PRL alone or in combination with progesterone or estradiol did not induce
      alphaERKO mammary growth. Estradiol and progesterone are required for the
      structural development of the alphaERKO mammary gland, and PRL contributes to
      this development by inducing ovarian progesterone levels. Therefore, the
      manifestation of the alphaERKO mammary phenotype appears due to the lack of
      direct estrogen action at the mammary gland and an indirect contributory role of
      estrogen signaling at the hypothalamic/pituitary axis.

PMID- 10919288
TI  - A common downstream signaling activity of osteoclast survival factors that
      prevent nitric oxide-promoted osteoclast apoptosis.
AB  - Treatment with NO-releaser NOC18 significantly promoted apoptosis in murine
      osteoclast-like cells, with a transient increase in caspase-3-like protease
      activity. In contrast, the apoptosis was protected against by caspase inhibitors,
      most efficiently with the broadly acting caspase specific inhibitor z-Asp-CH2
      DCB, indicating involvement of multiple caspases in progression of the apoptosis.
      Among osteoclast survival factors examined, calcitonin completely protected
      against morphologically defined-apoptosis and the increase of caspase-3-like
      protease activity. The effect of calcitonin was mimicked by treatment of cells
      with (Bu)2cAMP and forskolin, and abolished by protein kinase-A inhibitor H-89.
      Independently from the PKA activation, colony stimulating factor-1, interleukin
      1beta and the receptor activator of NF-kappaB ligand also protected against the
      apoptosis but were less effective than calcitonin. All survival factors
      investigated inhibited conversion of procaspases-3 and -9 to their mature forms
      in the cells. Thus, downstream antiapoptotic signaling activity from each factor
      overlapped in inhibition of caspases. However, how this was attained seemed to be
      different from each other. Typically, only colony stimulating factor-1 up
      regulated expression of endogenous caspase inhibitor protein, X-linked inhibitor
      of apoptosis (XIAP), in the osteoclast-like cells.

PMID- 10919289
TI  - Role of ascorbic acid in the osteoclast formation: induction of osteoclast
      differentiation factor with formation of the extracellular collagen matrix.
AB  - Osteoclasts are bone-resorbing multinucleated cells. Tartrate-resistant acid
      phosphatase-positive (TRAP-positive) mononuclear and multinucleated cells, which
      are osteoclast-like cells (OCLs), were formed as a result of the coculture of
      mouse bone marrow cells and clonal stromal ST2 cells in the presence of 1alpha,25
      dihydroxy-vitamin D3. Removal of ascorbic acid from the culture medium prevented
      the formation of TRAP-positive OCLs. Addition of ascorbic acid to the medium
      formed TRAP-positive OCLs, and the effect of ascorbic acid was dose-dependent.
      When we examined the level of messenger RNA (mRNA) for osteoclast differentiation
      factor (RANKL/ODF) in ST2 cells, we found that ascorbic acid caused an
      approximately 5-fold increase in the level of this mRNA. The half-life of the
      mRNA was unaffected by ascorbic acid. To characterize the mechanism of action of
      ascorbic acid, we investigated the relationship between formation of TRAP
      positive OCLs and formation of the collagen matrix. Inhibitors of the formation
      of collagen triple helices blocked both the formation of TRAP-positive OCLs and
      the expression of the mRNA for RANKL/ODF in response to ascorbic acid. Our
      findings suggest that ascorbic acid might be essential for osteoclastogenesis and
      might induce the formation of TRAP-positive OCLs via induction of the synthesis
      of RANKL/ODF that is somehow mediated by the extracellular matrix.

PMID- 10919290
TI  - Developmental and hormonal regulation of the expression of oligodendrocyte
      specific protein/claudin 11 in mouse testis.
AB  - The proliferation and differentiation of testicular progenitor stem cells into
      highly specialized germ cells (spermatozoa) are largely controlled by the
      hormonally (FSH and testosterone) regulated adjacent supporting Sertoli cells.
      However, the factors involved in this control remain largely unknown. In the
      present study, the technique of differential display PCR was used to identify
      target transcripts to FSH action in cultured murine Sertoli cells. Among these
      target transcripts, we identified the oligodendrocyte-specific protein (OSP),
      also known as claudin 11, which had recently been shown to play a key role in the
      formation of the hematotesticular barrier. Our data show that the testicular
      expression of OSP is dependent upon male gonad development and systemic and local
      signaling molecules. Indeed, OSP is expressed early in fetal development in
      Sertoli cells, immediately after the peak of SRY (sex-determining region, Y gene)
      expression, but just before that of the anti-Mullerian hormone. Postnatally, OSP
      expression starts to increase from day 3 to reach a plateau between days 6 and 16
      postnatally. In the prepubertal and adult testes, an apparent decline in OSP
      messenger RNA (mRNA) levels was found, probably because of the increasing number
      of germ cells (which do not express OSP). Among the signaling molecules that
      control testicular OSP expression, we have identified FSH and tumor necrosis
      factor-alpha (TNFalpha). Indeed, using a model of purified cultured mouse Sertoli
      cells, we demonstrate that FSH inhibits, in a dose (ED50 = 4 ng/ml)- and time
      (maximal effect after 24 h)-dependent manner, the levels of OSP mRNA. Such an
      inhibitory effect was mimicked by 8-bromo-cAMP, suggesting that FSH may use the
      cAMP/protein kinase A pathway to inhibit OSP mRNA levels. TNFalpha was also shown
      to inhibit OSP expression in cultured Sertoli cells. The maximal effect was
      observed after 48 h of TNFalpha treatment with an ED50 of 4.5 ng/ml. Together,
      our results indicate that OSP expression 1) starts during fetal life at a
      critical period, probably under SRY control and during testicular formation; and
      2) is regulated by hormones (FSH) and cytokines (TNFalpha) in the adult testis,
      suggesting a critical role for these molecules in the (re)modeling process of the
      hematotesticular barrier during spermatogenesis.

PMID- 10919292
TI  - Orthopedic surgery in Estonia.
AB  - We did a survey on the development of orthopedic surgery in Estonia, especially
      during the past 10 years, including education, hospital-based orthopedic surgery
      and orthopedic research. The main types of orthopedic operations were analyzed,
      on the basis of data from the Estonian Social Ministry, Bureau of Medical
      Statistics and several departments of orthopedic. On the average, 11,831
      orthopedic operations were performed yearly during the years 1996-1998 in
      hospital departments.

PMID- 10919291
TI  - Cell type-specific metabolism of peptidylglycine alpha-amidating monooxygenase in
      anterior pituitary.
AB  - Peptidylglycine alpha-amidating monooxygenase (PAM) is a bifunctional enzyme
      expressed in each major anterior pituitary cell type. We used primary cultures of
      adult male rat anterior pituitary to examine PAM expression, processing, and
      secretion in the different pituitary cell types and to compare these patterns to
      those observed in transfected AtT-20 corticotrope tumor cells. Immunostaining and
      subcellular fractionation identified PAM in pituitary secretory granules and
      additional vesicular compartments; in contrast, in AtT-20 cells, transfected PAM
      was primarily localized to the trans-Golgi network. PAM expression was highest in
      gonadotropes, with moderate levels in somatotropes and thyrotropes and lower
      levels in corticotropes and lactotropes. Under basal conditions, less than 1% of
      the cell content of monooxygenase activity was secreted per h, a rate comparable
      to the basal rate of release of individual pituitary hormones. General
      secretagogues stimulated PAM secretion 3- to 5-fold. Stimulation with specific
      hypothalamic releasing hormones demonstrated that different pituitary cell types
      secrete characteristic sets of PAM proteins. Gonadotropes and thyrotropes release
      primarily monofunctional monooxygenase. Somatotropes secrete primarily
      bifunctional PAM, whereas corticotropes secrete a mixture of mono- and
      bifunctional proteins. As observed in transfected AtT-20 cells, pituitary cells
      rapidly internalize the PAM/PAM-antibody complex from the cell surface. The
      distinctly different steady-state localizations of endogenous PAM in primary
      pituitary cells and transfected PAM in AtT-20 cell lines may simply reflect the
      increased storage capacity of primary pituitary cells.

PMID- 10919293
TI  - Late-diagnosed DDH: a prospective 11-year follow-up of 71 consecutive patients
      (75 hips).
AB  - I have prospectively studied 71 consecutive patients (75 hips) with late
      diagnosed DDH (developmental dysplasia of the hip) treated uniformly with special
      reference to the development of the femoral head and the acetabulum. The age at
      the start of treatment was 10 (2-64) months. The follow-up time was 11 (6-18)
      years. After tenotomy and traction, closed reduction failed in 7 hips. These
      cases were treated by open reduction with or without Salter innominate osteotomy
      in 2 hips femoral osteotomy was also done (shortening, varus and derotation). 1
      hip subluxated and 1 re-dislocated after closed reduction. Avascular necrosis
      occurred in 4 hips and additional surgery was required in 12 hips--11 Salter
      osteotomies, 1 varus femoral osteotomy. In the first year after reduction, the
      acetabular angle improved rapidly--faster in the younger children. When treatment
      started between 12 and 22 months, the improvement was slower and the final
      outcome more unpredictable. The femoral head continued to grow irrespective of
      the age at reduction and became normal in almost all cases. Salter's innominate
      osteotomy stabilized hips after open reduction and gave excellent results in
      cases with an increasing acetabular angle. At the last re-examination, all but 2
      patients were asymptomatic. Radiographically, 65 hips were rated Severin group I,
      9 group II and 1 group III.

PMID- 10919294
TI  - Alpine and cross-country skiing after total hip replacement: 2 cohorts of 50
      patients each, one active, the other inactive in skiing, followed for 5-10 years.
AB  - 2 groups of 50 patients each, matched for age, weight, height, gender and type of
      implant, were clinically and radiographically examined after THR. Group A
      regularly carried out alpine skiing and/or cross-country skiing, while group B
      did no winter sports. At 5 years, no signs of loosening were found in group A,
      whereas 5/60 implants in group B had signs of loosening, mostly of the femoral
      component (p < 0.05). At 10 years, 30 patients remained in group A and 27 in
      group B. No new cases of loosening were found in group B, but 2/30 cases in group
      A. There was a higher (p < 0.05) average wear rate in group A (2.1 mm) than in
      group B (1.5 mm). The wear rate was particularly high (3-4 mm) in physically very
      active patients in group A with localized osteolysis at the interface. It seems
      likely that in an even longer follow-up, the number of cases of aseptic loosening
      would be greater in group A than group B. Our findings, combined with the results
      of previously-published biomechanical studies, do not provide any evidence that
      controlled alpine and/ or cross-country skiing has a negative effect on the
      acetabular or femoral component of hip replacements. The results of the
      biomechanical studies indicate, however, that it is advantageous to avoid short
      radius turns on steep slopes or moguls.

PMID- 10919295
TI  - Tranexamic acid, given at the end of the operation, does not reduce postoperative
      blood loss in hip arthroplasty.
AB  - We performed a randomized double-blind study on the effect of tranexamic acid on
      postoperative blood loss and blood transfusions in 39 primary THR operations.
      Tranexamic acid was given at the end of the operation and 3 hours later.
      Ultrasound examination 1 week later was performed to measure the occurrence of
      deep hematomas. In contrast to previous findings in knee arthroplasty, the
      administration of tranexamic acid failed to give a significant reduction in the
      postoperative blood loss. This lack of effect was possibly related to the fact
      that the drug was administered too late. In 11 of the 20 patients receiving
      tranexamic acid, blood transfusion was not necessary, this being the case in 4/19
      in the placebo group (p = 0.05). The occurrence of postoperative deep venous
      thromboses was similar in the tranexamic acid and placebo groups.

PMID- 10919297
TI  - Patient satisfaction after knee arthroplasty: a report on 27,372 knees operated
      on between 1981 and 1995 in Sweden.
AB  - During a validation process of the Swedish Knee Arthroplasty Register (SKAR),
      living registered patients were sent a questionnaire to ask if they had been
      reoperated on. This gave an opportunity to pose a simple four-point question with
      respect to patient satisfaction which 95% of patients answered. We analyzed the
      answers of patients operated on between 1981 and 1995 and found that only 8% of
      the patients were dissatisfied regarding their knee arthroplasty 2-17 years
      postoperatively. The satisfaction rate was constant, regardless of when the
      operation had been performed during the 15-year period. The proportion of
      satisfied patients was affected by the preoperative diagnosis, patients operated
      on for a long-standing disease more often being satisfied than those with a short
      disease-duration. There was no difference in proportions of satisfied patients,
      whether they had primarily been operated on with a total knee arthroplasty (TKA)
      or a medial unicompartmental arthroplasty (UKA). For TKAs performed with primary
      patellar resurfacing, there was a higher ratio of satisfied patients than for
      TKAs not resurfaced, but this increased ratio diminished with time passed since
      the primary operation. Unrevised knees had a higher proportion of satisfied
      patients than knees that had been subject to revision, and among patients revised
      for medial UKA, the proportion of satisfied patients was higher than among
      patients revised for TKA. We conclude that satisfaction after knee arthroplasty
      is stable and long-lasting in unrevised cases and that even after revision most
      patients are satisfied.

PMID- 10919296
TI  - Macrophage-osteoclast differentiation and bone resorption in osteoarthrotic
      subchondral acetabular cysts.
AB  - A macrophage infiltrate is commonly found in enlarging subchondral cysts in
      osteoarthrosis (OA) and the surrounding bone. To determine whether osteoclast
      differentiation by these cells contributes to the increase in the number of
      osteoclasts and bone resorption that accompanies OA cyst enlargement, we isolated
      macrophages from the wall of OA cysts and co-cultured them with osteoblast-like
      UMR106 cells in the presence or absence of 1,25(OH)2D3 and M-CSE After 14 days of
      incubation, co-cultures of UMR106 cells and cyst-derived macrophages showed
      evidence of osteoclast differentiation by expression of TRAP, VNR and formation
      of numerous lacunar pits. We found that, unlike osteoclast precursors in monocyte
      and other tissue macrophage populations, the addition of M-CSF to medium is not
      required for osteoclast differentiation. Our findings suggest that macrophage
      osteoclast differentiation is one means whereby the osteolysis associated with
      the enlargement of OA cysts could be effected.

PMID- 10919299
TI  - Semitendinosus tendon graft ingrowth in tibial tunnel following ACL
      reconstruction: a histological study of 2 patients with different types of early
      graft failure.

PMID- 10919298
TI  - Translation and validation of the Oxford-12 item knee score for use in Sweden.
AB  - The Oxford-12 Item Knee Score is a recently developed and validated patient
      completed outcome measure designed specifically for use with knee arthroplasty in
      the United Kingdom. We have translated this questionnaire into Swedish and tested
      the validity and reliability of the translated version in a cross-sectional study
      by a postal survey to 1,200 randomly selected patients from the Swedish Knee
      Arthroplasty Register. Swedish versions of the WOMAC, Nottingham Health Profile,
      SF-36, SF-12, and the Sickness Impact Profile were employed in the validation
      process. We also tested feasibility and patient-burden parameters. The translated
      version appeared to be linguistically and culturally equivalent to the original
      version with good validity and reliability. Indirect measures of responsiveness
      indicated that it is at least as responsive to relevant knee arthroplasty patient
      states as the previously validated Swedish version of the WOMAC. Application of
      the translated questionnaire to this population is feasible with minimal imposed
      patient-burden. The Swedish translation of the Oxford-12 Item Knee Score is a
      valid and reliable tool for outcome studies on knee arthroplasty patients.

PMID- 10919300
TI  - Intraarticular morphine after arthroscopic ACL reconstruction: a double-blind
      placebo-controlled study of 40 patients.
AB  - We compared analgesic effects and pharmacokinetics of intraarticular versus
      intravenous administration of morphine after arthroscopic anterior cruciate
      ligament surgery. In a double-blind placebo-controlled study, 40 patients were
      randomly allocated to one of four treatment groups. Group I received 1 mg
      morphine intraarticularly and saline intravenously; group II received 5 mg
      morphine intraarticularly and saline intravenously; group III received 5 mg
      saline intraarticularly and morphine intravenously and group IV, the control
      group, received saline both intraarticularly and intravenously. The pain scores
      were significantly lower in groups I and II at 24 hours postoperatively than in
      group IV, and in group II during the rest of the postoperative period, as
      compared to groups III and IV. After intraarticular injection of 1 mg and 5 mg
      morphine, respectively, low concentrations of morphine-6-glucuronide (M6G) were
      found in the circulation, while morphine-3-glucuronide (M3G) appeared late after
      the injection in concentrations that considerably exceeded those of morphine in
      groups I and II. The analgesic effect of intraarticular morphine together with
      the low levels of morphine and morphine-6-glucuronide in plasma further
      strengthens the view that opioids have a peripheral mechanism of action.

PMID- 10919301
TI  - Tibial tubercle malposition in patellar joint instability: a computed tomograpy
      study in full extension and at 30 degree flexion.
AB  - We evaluated the tibial tubercle position in knees with patellar instability. CT
      in full extension and at 30 degree flexion was used in 18 knees with instability
      and 18 control knees. Scans were taken at the level of the femoral epicondyles,
      tibial tubercle and distal tibia. We found that in full extension, the tibial
      tubercle was in a more lateral position in the unstable than in the control
      knees. At 30 degree flexion, the tibial tubercle in the unstable knees rotated
      internally, but it was never within the normal range. CT scans taken in full
      extension and at 30 degree flexion seem to be of value for ascertaining the
      degree of tibial tubercle malposition during knee flexion in patellar
      instability.

PMID- 10919302
TI  - Repair of lumbar spondylolysis using Morscher material: 14 children followed for
      1-5 years.
AB  - We evaluated the results of spondylolysis repair in children and adolescents with
      the Morscher system. 14 patients (8 girls) with symptomatic spondylolysis
      unresponsive to closed treatment were operated on. Mean age at operation was 12
      (7-15) years. The average follow-up was 33 (16-66) months. Results were assessed
      clinically according to the Henderson classification and radiographically.
      Clinical results were excellent in 9 patients, good in 4 and poor in 1.
      Radiographs showed that fusion was obtained in 12 patients, it was doubtful in 1
      and 1 patient had non-union. Loosening of the screw on one or both sides was
      noted in 8 patients and necessitated removal of the osteosynthesis material
      which, however, did not alter the final outcome. The satisfactory results
      obtained in our series are similar to those reported in the literature.

PMID- 10919303
TI  - Ankle arthrodesis using the Ilizarov apparatus: good results in 6 patients.
AB  - We report our experience with the Ilizarov apparatus in performing ankle
      arthrodesis in 6 patients. The average age of the patients was 52 (42-60) years.
      3 patients had posttraumatic arthrosis and active infection of the ankle or
      distal tibia and the other 3 had posttraumatic arthrosis of the ankle without
      infection. Solid and painless arthrodesis was achieved in all patients in 7-15
      weeks, including those with an active infection or failed multiple previous
      operations. While the method is useful for primary treatment of ankle arthrosis,
      we think it is better for treatment of certain complicated cases.

PMID- 10919304
TI  - Intraarticular glucocorticoid, morphine and bupivacaine reduces pain and
      convalescence after arthroscopic ankle surgery: a randomized study of 36
      patients.
AB  - In a double-blind randomized study, 36 patients undergoing arthroscopic removal
      of bony spurs and synovitis causing impingement of the ankle were allocated to
      intraarticular saline or bupivacaine 15 mg + morphine 5 mg + intraarticular
      methylprednisolone 40 mg. Combined methylprednisolone, bupivacaine and morphine
      reduced pain, joint swelling, time of immobilization, duration of sick leave and
      return to sports after the arthroscopic procedure. In the treatment group, 1
      patient had transitory purulent arthritis requiring antibiotics and arthroscopic
      synovectomy occurred.

PMID- 10919305
TI  - Large tumor endoprostheses and extracortical bone-bridging: 28 patients followed
      10-20 years.
AB  - Aseptic loosening is a common cause of failure in large tumor endoprostheses. The
      concept of extracortical bone-bridging was developed to tackle the problem of
      loosening. New bone which forms across the junction of the bone-prosthesis
      junction is believed to improve fixation by controlling the transfer of stresses
      across the junction as well as by giving additional stability to the prosthesis.
      We present the long-term experience with this concept following major
      reconstruction after tumor and non-tumor conditions in 31 patients. The overall
      function was good for upper and lower limb prostheses. Most patients had
      extracortical bone bridging which was maintained for over 10 years. In 1/3 of
      patients this involved over 75% of the prosthetic circumference. Prosthetic
      survival was best with intercalary devices, followed by proximal femoral and
      distal femoral prostheses. Survival of prostheses in young active patients was
      similar to that reported in older patients undergoing primary joint replacement.

PMID- 10919306
TI  - Bone and joint tuberculosis in Denmark: increase due to immigration.
AB  - We studied the epidemiology of bone and joint tuberculosis (TB) in Denmark during
      the period 1993-1997, using data in the national Danish TB register. We found 95
      cases, accounting for 4% of all tuberculosis cases and 15% of extrapulmonary
      cases, giving a mean annual incidence of 0.4 per 10(5) in the period. 26 cases
      were found among native Danes (3-8 cases per year) with a median age of 66 (10
      92) years and giving a mean annual incidence of 0.1 per 10(5). Among immigrants,
      an increasing number of cases of bone and joint TB were diagnosed, increasing
      from 5 in 1993 to 28 in 1997, giving a total of 69 cases with a mean age of 35
      (11-75) years and a mean annual incidence of 4 per 10(5) in the period. The spine
      was affected in half of the cases. 28 patients had active TB elsewhere in the
      same period. In most patients, there were no predisposing or risk factors for
      disease except for ethnicity. Compared to a study of bone and joint TB in Denmark
      in the 1980s, the total incidence is the same, but there has been a shift in
      patients from old Danes to young immigrants. The increasing number of bone and
      joint TB cases among immigrants is due to recent immigration of Somalian
      refugees, who have a high incidence of TB and a high proportion of extrapulmonary
      TB. The diagnosis was often delayed several months or years. This study shows
      that attention must be paid to this condition, particularly in young patients
      from an endemic immigrant population.

PMID- 10919307
TI  - Systemic corticosteroids inhibit bone healing in a rabbit ulnar osteotomy model.
AB  - Prolonged systemic administration of corticosteroids causes osteoporosis and
      increased risk of fracture. Despite this well documented side effect of systemic
      corticosteroids, the effect of these compounds on fracture healing is not well
      defined. The goal of this study was to test the hypothesis that systemic
      corticosteroid therapy adversely affects fracture healing in a rabbit ulnar
      osteotomy model. Non-critical sized (1 mm) defects were created bilaterally in 18
      adult female New Zealand White rabbits. Starting 2 months before operative
      intervention and continuing for 6 weeks during healing of the osteotomies, a
      subcutaneous dose of either sterile saline or prednisone (0.15 mg/kg) was
      administered daily. Serial radiographs of the forelimb were taken immediately
      postoperatively and weekly beginning the second week postoperatively. After
      killing at 6 weeks, only 3 of 20 limbs from animals treated with prednisone
      achieved radiographic union while 13 of 16 control limbs achieved union. The
      radiographic density of bone in the defect as well as callus size were greater in
      the control limbs than in the limbs from prednisone-treated animals. DEXA
      confirmed that the bone mineral content was lower in the ulnae of prednisone
      treated rabbits both within the defect and in adjacent ulnar bone. Mechanical
      data indicated that osteotomies from rabbits chronically treated with prednisone
      were weaker than in controls. In this rabbit ulnar osteotomy model, chronic
      prednisone treatment clearly inhibited bone healing.

PMID- 10919308
TI  - Femoral neuropathy caused by enlarged iliopsoas bursa associated with
      osteonecrosis of femoral head--a case report.

PMID- 10919309
TI  - Dislocating medial head of triceps--awareness of the condition could avoid
      inappropriate surgery--a case report.

PMID- 10919310
TI  - Increased levels of chondrocalcin in knee joint fluid in synovial chondromatosis-
      a case report.

PMID- 10919311
TI  - Delayed diagnosis and treatment of Tillaux fracture--a case report.

PMID- 10919312
TI  - Fibrosarcoma at the site of a metallic fixation of the tibia--a case report and
      literature review.

PMID- 10919313
TI  - Part I. Epidemiology of ductal carcinoma in situ.

PMID- 10919314
TI  - Part II. Medical imaging of ductal carcinoma in situ.

PMID- 10919315
TI  - Part III. The pathobiology of ductal carcinoma in situ.

PMID- 10919316
TI  - Part IV. Surgery for ductal carcinoma in situ.

PMID- 10919317
TI  - Part V. Adjuvant therapies for ductal carcinoma in situ.

PMID- 10919318
TI  - Bacteriorhodopsin: mutating a biomaterial into an optoelectronic material.
AB  - Bacteriorhodopsin (BR) is the key protein for the halobacterial photosynthetic
      capabilities and is one of the very rare molecules which occur in crystalline
      form in nature. Since its discovery, which was reported in 1971, many efforts
      have been made to exploit the obvious technical potential of this molecule.
      Successful application of gene technology methods for the modification of the
      physical function of a biomolecule was first demonstrated with BR. This approach
      points the way to a new class of materials derived from evolutionary optimized
      biomaterials by genetic re-engineering. Mutated BRs proved to have significant
      advantages over the wild type in optical applications. The current status of
      potential technical applications of BR is reviewed. BR is employed as a
      photoelectric, photochromic or energy-converting element. First systems now exist
      which demonstrate the successful integration of this new material into existing
      technologies. Analyzing the patents filed, which claim the processing or
      application of BR, gives an indication to areas where further technical uses are
      to be expected in the near future.

PMID- 10919319
TI  - Efficient secretory production of alkaline phosphatase by high cell density
      culture of recombinant Escherichia coli using the Bacillus sp. endoxylanase
      signal sequence.
AB  - New secretion vectors containing the Bacillus sp. endoxylanase signal sequence
      were constructed for the secretory production of recombinant proteins in
      Escherichia coli. The E. coli alkaline phosphatase structural gene fused to the
      endoxylanase signal sequence was expressed from the trc promoter in various E.
      coli strains by induction with IPTG. Among those tested, E. coli HB101 showed the
      highest efficiency of secretion (up to 25.3% of total proteins). When cells were
      induced with 1 mM IPTG, most of the secreted alkaline phosphatase formed
      inclusion bodies in the periplasm. However, alkaline phosphatase could be
      produced as a soluble form without reduction of expression level by inducing with
      less (0.01 mM) IPTG, and greater than 90% of alkaline phosphatase could be
      recovered from the periplasm by the simple osmotic shock method. Fed-batch
      cultures were carried out to examine the possibility of secretory protein
      production at high cell density. Up to 5.2 g/l soluble alkaline phosphatase could
      be produced in the periplasm by the pH-stat fed-batch cultivation of E. coli
      HB101 harboring pTrcS1PhoA. These results demonstrate the possibility of
      efficient secretory production of recombinant proteins in E. coli by high cell
      density cultivation.

PMID- 10919320
TI  - Economic considerations in the production of poly(3-hydroxybutyrate-co-3
      hydroxyvalerate) by bacterial fermentation.
AB  - The process for the production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate)
      [P(3HB/V)] by bacterial fermentation and its recovery was analysed. The effects
      of various factors such as P(3HB/V) content, P(3HB/V) productivity, P(3HB/V)
      yield and 3-hydroxyvalerate (3HV) fraction in P(3HB/V) on the production cost of
      P(3HB/V) were examined. The increase in the 3HV yield on a carbon source did not
      significantly decrease the production cost when the 3HV fraction was 10 mol%,
      because the cost of the carbon substrate for 3HV was relatively small in terms of
      the total cost. However, at a 3HV fraction of 30 mol%, the 3HV yield on a carbon
      source had a significant effect on the total P(3HB/V) production cost. The
      production cost of P(3HB/V) increased linearly with the increase in the 3HV
      fraction in P(3HB/V).

PMID- 10919321
TI  - Acoustic demixing of aqueous two-phase systems.
AB  - Aqueous two-phase systems demix slowly due to similar physical properties. This
      is one of the major drawbacks for their adaptation for industrial scale
      extraction of enzymes. In the present work, a method to accelerate the demixing
      rates of these systems, employing a traveling acoustic wave field is reported for
      the first time. Phase-demixing for three systems, viz. polyethylene glycol
      (PEG)/sodium sulfate, PEG/potassium phosphate and PEG/maltodextrin were studied.
      The acoustically assisted process decreased the demixing time significantly
      (about 2- to 3-fold in PEG/salt systems and about 2-fold in the PEG/maltodextrin
      system), compared to that in gravity alone. Ultrasonication apparently enhanced
      the coalescence of the dispersed phase droplets due to the mild circulation
      currents it caused in the dispersion. This in turn enhanced the rate of demixing
      due to the increased migration velocity of the larger droplets.

PMID- 10919322
TI  - Production of interferon-alpha in high cell density cultures of recombinant
      Escherichia coli and its single step purification from refolded inclusion body
      proteins.
AB  - Escherichia coli TG1 transformed with a temperature-regulated interferon-alpha
      expression vector was grown to high cell density in defined medium containing
      glucose as the sole carbon and energy source, utilizing a simple fed-batch
      process. Feeding was carried out to achieve an exponential increase in biomass at
      growth rates which minimized acetate production. Thermal induction of such high
      cell density cultures resulted in the production of approximately 4 g interferon
      alpha/l culture broth. Interferon-alpha was produced exclusively in the form of
      insoluble inclusion bodies and was solubilized under denaturing conditions,
      refolded in the presence of arginine and purified to near homogeneity, utilizing
      single-step ion-exchange chromatography on Q-Sepharose. The yield of purified
      interferon-alpha was approximately 300 mg/l with respect to the original high
      cell density culture broth (overall yield of approximately 7.5% active interferon
      alpha). The purified recombinant interferon-alpha was found by different criteria
      to be predominantly monomeric and possessed a specific bioactivity of
      approximately 2.5 x 10(8) IU/mg based on viral cytopathic assay.

PMID- 10919323
TI  - A comparison of enzyme-aided bleaching of softwood paper pulp using combinations
      of xylanase, mannanase and alpha-galactosidase.
AB  - Enzymatic pretreatment of softwood kraft pulp was investigated using xylanase A
      (XylA) from Neocallimastix patriciarum in combination with mannanase and alpha
      galactosidase. Mannanase A (ManA) from Pseudomonas fluorescens subsp. cellulosa
      and ManA from Clostridium thermocellum, both family 26 glycosyl hydrolases, are
      structurally diverse and exhibit different pH and temperature optima. Although
      neither mannanase was effective in pretreating softwood pulp alone, both enzymes
      were able to enhance the production of reducing sugar and the reduction of single
      stage bleached kappa number when used with the xylanase. Sequential incubations
      with XylA and P. fluorescens ManA produced the largest final kappa number
      reduction in comparison to control pretreated pulp. The release of galactose from
      softwood pulp by alpha-galactosidase A (AgaA) from P. fluorescens was enhanced by
      the presence of ManA from the same microorganism, and a single pretreatment with
      these enzymes, in combination with XylA. gave the most effective kappa number
      reduction using a single incubation. Results indicated that mixtures of
      hemicellulase activities can be chosen to enhance pulp bleachability.

PMID- 10919324
TI  - Investigating expression systems for the stable large-scale production of
      recombinant L-leucine-dehydrogenase from Bacillus cereus in Escherichia coli.
AB  - The established Escherichia coli expression vectors ptrc99a, pKK223-3, pPLlambda,
      pAsk75, pRA95, and pRA96, which differ in copy number, mode of induction,
      selection marker, and use of par sequences for stabilization, were investigated
      for the stable expression of recombinant L-leucine dehydrogenase from Bacillus
      cereus with a view to large-scale production. Best results were achieved with
      pIET98, a runaway-replication system derived from pRA96. Expression of L-leucine
      dehydrogenase was controlled by its constitutive B. cereus promoter and depended
      on host strain, cultivation temperature, induction time, and media composition.
      After cell cultivation at 30 degrees C and shifting to 41 degrees C to induce
      plasmid replication, E. coli BL21[pIET98] yielded 200 U LeuDH/mg protein, which
      corresponds to >50% of the soluble cell protein. Continuous cultivation in a
      semisynthetic high-cell-density medium verified structural and segregational
      stability over 100 generations in the absence of a selection pressure.

PMID- 10919325
TI  - Production of riboflavin by metabolically engineered Corynebacterium
      ammoniagenes.
AB  - Improved strains for the production of riboflavin (vitamin B2) were constructed
      through metabolic engineering using recombinant DNA techniques in Corynebacterium
      ammoniagenes. A C. ammoniagenes strain harboring a plasmid containing its
      riboflavin biosynthetic genes accumulated 17-fold as much riboflavin as the host
      strain. In order to increase the expression of the biosynthetic genes, we
      isolated DNA fragments that had promoter activities in C. ammoniagenes. When the
      DNA fragment (P54-6) showing the strongest promoter activity in minimum medium
      was introduced into the upstream region of the riboflavin biosynthetic genes, the
      accumulation of riboflavin was 3-fold elevated. In that strain, the activity of
      guanosine 5'-triphosphate (GTP) cyclohydrolase II, the first enzyme in riboflavin
      biosynthesis, was 2.4-fold elevated whereas that of riboflavin synthase, the last
      enzyme in the biosynthesis, was 44.1-fold elevated. Changing the sequence
      containing the putative ribosome-binding sequence of 3,4-dihydroxy-2-butanone 4
      phosphate synthase/GTP cyclohydrolase II gene led to higher GTP cyclohydrolase II
      activity and strong enhancement of riboflavin production. Throughout the strain
      improvement, the activity of GTP cyclohydrolase II correlated with the
      productivity of riboflavin. In the highest producer strain, riboflavin was
      produced at the level of 15.3 g l(-1) for 72 h in a 5-l jar fermentor without any
      end product inhibition.

PMID- 10919326
TI  - Generation of aflR disruption mutants of Aspergillus parasiticus.
AB  - The aflR gene of Aspergillus parasiticus and A. flavus encodes a binuclear zinc
      finger, DNA-binding protein, AflR, responsible for activating the transcription
      of all known aflatoxin biosynthetic genes including itself. Studies to determine
      how environmental and nutritional factors affect aflR expression and hence
      aflatoxin production in A. parasiticus have been difficult to perform due to the
      lack of aflR "knockout" mutants. Transformation of an O-methylsterigmatocystin
      (OMST)-accumulating strain of A. parasiticus with an aflR-niaD gene disruption
      vector resulted in clones harboring a recombinationally inactivated aflR gene
      which no longer produced OMST or aflR transcript. By transformation of this aflR
      disruptant strain with constructs containing mutated versions of the aflR
      promoter, we identified three cis-acting sites that were necessary for aflR
      function: an AflR-binding site, a PacC-binding site, and a G + A-rich site near
      the transcription start site of aflR.

PMID- 10919327
TI  - Cloning, characterization and expression of an Enterococcus faecalis gene
      responsive to heavy metals.
AB  - Gene encoding stress response proteins are induced by a variety of environmental
      stimuli including the presence of heavy metals. To address the utility of this
      response for pollutant detection, one cadmium-induced gene in Enterococcus
      faecalis was isolated, sequenced and studied at the transcriptional level. csrA
      contains an open reading frame encoding a protein of 168 amino acids with
      homology to the enzyme peptide methionine sulfoxide reductase. The csrA mRNA was
      barely present in unstressed E. faecalis cells grown in M17-glucose medium, but
      accumulated at higher levels in cadmium-treated cells. Mercury also had an effect
      on csrA expression, whereas lead, copper and manganese induced csrA expression
      only at the highest doses tested. Our results suggest that biosensors based on E.
      faecalis may have potential applications for environmental monitoring and should
      be constructed.

PMID- 10919328
TI  - Rapid and specific identification of medium-chain-length polyhydroxyalkanoate
      synthase gene by polymerase chain reaction.
AB  - A polymerase chain reaction (PCR) protocol was developed for the specific
      detection of genes coding for type II polyhydroxyalkanoate (PHA) synthases. The
      primer-pair, I-179L and I-179R, was based on the highly conserved sequences found
      in the coding regions of Pseudomonas phaC1 and phaC2 genes. Purified genomic DNA
      or lysate of colony suspension can serve equally well as the target sample for
      the PCR, thus affording a simple and rapid screening of phaC1/C2-containing
      microorganisms. Positive samples yield a specific 540-bp PCR product representing
      partial coding sequences of the phaC1/C2 genes. Using the PCR method, P.
      corrugata 388 was identified for the first time as a medium-chain-length (mcl)
      PHA producer. Electron microscopic study and PHA isolation confirmed the
      production of mcl-PHA in P. corrugata 388. The mcl-PHA of this organism has a
      higher molecular weight than that of similar polymers produced by other
      pseudomonads.

PMID- 10919329
TI  - Conversion of 1-benzoylindole by Aspergillus strains.
AB  - Biotransformation of 1-benzoylindole (BI) by the strains Aspergillus flavus VKM F
      1024 and Aspergillus oryzae VKM F-44 was studied. The major metabolites isolated
      were identified as 4-hydroxyindole (4-HI), 5-hydroxyindole (5-HI), 4-hydroxy- 
      benzoylindole, 4-hydroxy-1-(4'-hydroxy)-benzoylindole and indole. The structure
      of the metabolites was determined by mass spectrometry and proton nuclear
      magnetic resonance spectroscopy. The pathways of BI metabolism via initial
      monohydroxylation at C-4 and C-5 followed by cleavage of the benzoyl substituent
      to yield 4-HI and 5-HI were proposed. Indole was formed as a by-product, and its
      role as a potent inhibitor of BI hydroxylation at C-4 and C-5 is discussed.

PMID- 10919330
TI  - Physiological effects of 5-hydroxymethylfurfural on Saccharomyces cerevisiae.
AB  - The physiological effects of 5-hydroxymethylfurfural (HMF) on Saccharomyces
      cerevisiae CBS 8066 in the presence and absence of furfural were studied.
      Experiments were carried out by pulse addition of HMF (2-4 g/l) as well as HMF (2
      g/l) together with furfural (2 g/l) to batch cultivations of S. cerevisiae.
      Synthetic medium with glucose (50 g/l) as carbon and energy source was used.
      Addition of 4 g/l of HMF caused a decrease (approx. 32%) in the carbon dioxide
      evolution rate. Furthermore, the HMF was found to be taken up and converted by
      the yeast with a specific uptake rate of 0.14 (+/-0.03) g/g x h during both
      aerobic and anaerobic conditions, and the main conversion product was found to be
      5-hydroxymethylfurfuryl alcohol. A previously unreported compound was found and
      characterized by mass spectrometry. It is suggested that the compound is formed
      from pyruvate and HMF in a reaction possibly catalysed by pyruvate decarboxylase.
      When HMF was added together with furfural, very little conversion of HMF took
      place until all of the furfural had been converted. Furthermore, the conversion
      rates of both furfural and HMF were lower than when added separately and growth
      was completely inhibited as long as both furfural and HMF were present in the
      medium.

PMID- 10919331
TI  - Protective effect of the bile salt hydrolase-active Lactobacillus reuteri against
      bile salt cytotoxicity.
AB  - Bacterial bile salt hydrolysis is considered a risk factor for the development of
      colon cancer because of the risk of forming harmful secondary bile salts after an
      initial deconjugation step. In this study, the influence of enhanced bacterial
      bile salt transformation by the bile salt hydrolase-active Lactobacillus reuteri
      was studied in batch culture using the microbial suspension of the Simulator of
      the Human Intestinal Microbial Ecosystem; (SHIME), which was supplemented with
      oxgall at 5 g/l or 30 g/l. Changes in the fermentative capacity of the microbial
      ecosystem and the (geno)toxic properties of the SHIME supernatants were
      investigated. Increasing concentrations of oxgall inhibited the fermentation.
      Transient cell toxicity was observed for samples supplemented with 5 g oxgall/l,
      while samples with 30 g oxgall/l exhibited toxicity. The results of the
      haemolysis test suggest that the detrimental effects were probably due to the
      membrane-damaging effects of bile salts. In all cases, the adverse effects could
      be counteracted by the addition of 7.5 +/- 0.5 log10 CFU L. reuteri/ml. Plausible
      mechanisms for the protective properties of L. reuteri could involve a
      precipitation of the deconjugated bile salts and a physical binding of bile salts
      by the bacterium, thereby making the harmful bile salts less bioavailable.

PMID- 10919332
TI  - A highly thermostable endo-(1,4)-beta-mannanase from the marine bacterium
      Rhodothermus marinus.
AB  - Rhodothermus marimus ATCC 43812, a thermophilic bacterium isolated from marine
      hot springs, possesses hydrolytic activities for depolymerising substrates such
      as carob-galactomannan. Screening of expression libraries identified mannanase
      positive clones. Subsequently, the corresponding DNA sequences were determined,
      eventually identifying a coding sequence specifying a 997 amino acid residue
      protein of 113 kDa. Analyses revealed an N-terminal domain of unknown function
      and a C-terminal mannanase domain of 550 amino acid residues with homology to
      known mannanases of glycosidase family 26. Action pattern analysis categorised
      the R. marinus mannanase as an endo-acting enzyme with a requirement for at least
      five sugar moieties for effective catalytic activity. When expressed in
      Escherichia coli, purified gene product with catalytic activity was mainly found
      as two protein fragments of 45 kDa and 50 kDa. The full-length protein of 113 kDa
      was only detected in crude extracts of R. marinus, while truncated protein
      containing fractions of the original source resulted in a major active protein of
      60 kDa. Biochemical analysis of the mannanase revealed a temperature and pH
      optimum of 85 degrees C and pH 5.4, respectively. Purified, E. coil-produced
      protein fragments showed high heat stability, retaining more than 70% and 25% of
      the initial activity after 1 h incubation at 70 degrees C and 90 degrees C,
      respectively. In contrast, R. marinus-derived protein retained 87% activity after
      1 h at 90 degrees C. The enzyme hydrolysed carob-galactomannan (locust bean gum)
      effectively and to a smaller extent guar gum, but not yeast mannan.

PMID- 10919333
TI  - A simplification of the protein assay method of Ramsay et al. for the
      quantification of Thiobacillus ferrooxidans in the presence of ferric
      precipitates.
AB  - A variation on Ramsay's method for microbial protein determination has been
      developed in order to quantify Thiobacillus ferrooxidans attached to ferric
      precipitates or in aqueous suspensions containing such precipitates. Some
      modifications have been introduced to provide a method that is more sensitive,
      simple and rapid. A linear standard curve is presented to permit a direct
      correlation between the protein concentration (mg/l) and the cell concentration
      (10(6) cells/ml). An application of this method has been demonstrated in the
      quantification of biomass immobilized on the surface of polyurethane foam
      particles in a packed bed reactor, several experiments having been conducted to
      establish the best conditions for the quantification studies.

PMID- 10919334
TI  - Inhibition of methane production from whey by heavy metals--protective effect of
      sulfide.
AB  - A whey solution was used as a substrate for methane production in an anaerobic
      fixed-bed reactor. At a hydraulic retention time of 10 days, equivalent to a
      space loading of 3.3 kg (m3 day)(-1), 90% of the chemical oxygen demand was
      converted to biogas. Only a little propionate remained in the effluent. Toxicity
      tests with either copper chloride, zinc chloride or nickel chloride were
      performed on effluent from the reactor. Fifty per cent inhibition of
      methanogenesis was observed in the presence of > or =10 mg CuCl2 l(-1) > or =40
      mg ZnCl2 l(-1) and > or =60 mg NiCl2 l(-1), respectively. After exposure to Cu2+,
      Zn2+ or Ni2+ ions for 12 days, complete recovery of methanogenesis by equimolar
      sulfide addition was possible upon prolonged incubation. Recovery failed,
      however, for copper chloride concentrations > or =40 mg l(-1). If the sulfide was
      added simultaneously with the three heavy metal salts, methanogenesis was only
      slightly retarded and the same amount of methane as in non-inhibited controls was
      reached either 1 day (40 mg ZnCl2 l(-1) or 2 days later (10 mg CuCl2 l(-1)). Up
      to 60 mg NiCl2 l(-1) had no effect if sulfide was present. Sulfide presumably
      precipitated the heavy metals as metal sulfides and by this means prevented heavy
      metal toxicity.

PMID- 10919336
TI  - Bioluminescent most-probable-number monitoring of a genetically engineered
      bacterium during a long-term contained field release.
AB  - Pseudomonas fluorescens HK44 is a lux-based bioluminescent bioreporter capable of
      emitting light upon exposure to naphthalene, salicylate, and other substituted
      analogs. The bacterium was inoculated into intermediate-scale field lysimeters
      and population dynamics were monitored with time. Two methods were used to
      enumerate cell numbers in soil: a standard selective plating technique with
      colony hybridization verification and a modified lux-based most-probable-number
      (lux-MPN) assay based on the detection of bioluminescence. The lux-MPN assay was
      developed and evaluated as a possible supplement or replacement for the labor
      intensive and time-consuming selective plating assay. Comparisons between
      selective plate counts and lux-MPN population estimates showed similar trends
      over the 2-year study, except that lux-MPN estimates were consistently less than
      selective plate counts. Verification of P. fluorescens HK44 genotype through
      colony hybridization techniques revealed that selective plating was actually
      overestimating HK44 populations and that lux-MPN values were more closely
      approximating true HK44 cell densities, except within the first few weeks after
      inoculation, when lux-MPN estimates underrepresented population densities. Thus,
      utilizing bioluminescence as a population monitoring tool for lux-based
      microorganisms was shown to be more effective and precise than standard selective
      plating techniques, and provided an accurate ecological analysis of P.
      fluorescens HK44 population dynamics over an extended period.

PMID- 10919335
TI  - A note on the estimation of microbial glycosidase activities by dinitrosalicylic
      acid reagent.
AB  - In the estimation of glycosidase activity by dinitrosalicylic acid (DNS) reagent,
      the stoichiometry of DNS reduction was reported to increase proportionately with
      the increase in the number of glycosidic linkages present in oligosaccharides
      liberated by the enzyme. The relationship between increases in DNS reduction and
      increases in the number of glycosidic bonds was found to be represented by a part
      of a rectangular hyperbola. The increase was optimum with disaccharide and
      insignificant when the degree of polymerization (DP) was > or =10. The difference
      did not arise as a result of the DNSA discriminating between mono- and
      oligosaccharide oxidation. The relationship stemmed from the acidity of the
      hydroxyl group adjacent to the reducing group, which repressed DNS reduction. The
      acidity is likely to decrease with an increase in oligosaccharide chain length.
      It is suggested that DNS reduction is actually optimum and uniform for all
      oligosaccharides of DP > or = 10 and that it is minimum for monosaccharide. Thus
      the introduction of rectification factors in the estimation of glycosidase
      activities by the DNS method appears to be justified.

PMID- 10919337
TI  - Comparison of the spatial homogeneity of physico-chemical parameters and
      bacterial 16S rRNA genes in sediment samples from a dumping site for dredging
      sludge.
AB  - The homogeneity of the microbial community structure of a sediment landfill was
      examined by a culture-independent method and compared with physico-chemical
      parameters, i.e. organic matter, CaCO3 content, pH, and texture. Total genomic
      DNA was extracted from samples derived from different places and depths. After
      amplification with two different primer sets of partial bacterial 16S rRNA genes,
      the products were separated by denaturing gradient gel electrophoresis (DGGE).
      The DGGE fingerprints of different sediment samples taken in regular patterns at
      the same depth were similar, which indicates a spatial homogeneity in the
      numerically dominant bacterial populations in a landfill over 10,000 m2 in size.
      In a vertical column of approx. 10 m, only some differences in a few bands of the
      bacterial community structure were observed between samples taken from different
      depths. This DNA homogeneity coincided with a similar homogeneity of the physico
      chemical parameters in the landfill at this site. Nevertheless, the DGGE
      technique revealed small differences in less prominent bacteria and was capable
      of separating the upper and lower samples of one column into two clusters. It
      therefore seems more sensitive than the physico-chemical approach for
      characterising the homogeneity of an environmental habitat.

PMID- 10919338
TI  - Broad substrate specificity of naphthalene- and biphenyl-utilizing bacteria.
AB  - Although aromatic compounds are most often present in the environment as
      components of complex mixtures, biodegradation studies commonly focus on the
      degradation of individual compounds. The present study was performed to
      investigate the range of aromatic substrates utilized by biphenyl- and
      naphthalene-degrading environmental isolates and to ascertain the effects of co
      occurring substrates during the degradation of mono-aromatic compounds. Bacterial
      strains were isolated on the basis of their ability to utilize either biphenyl or
      naphthalene as a sole source of carbon. Growth and transformation assays were
      conducted on each isolate to determine the range of substrates degraded. One
      isolate, Pseudomonas putida BP18, was tested for the ability to biodegrade
      benzene, toluene, ethylbenzene and xylene isomers (BTEX) individually and as
      components of mixtures. Overall, the results indicate that organisms capable of
      growth on multi-ring aromatic compounds may be particularly versatile in terms of
      aromatic hydrocarbon biodegradation. Furthermore, growth and transformation
      assays performed with strain BP18 suggest that the biodegradation of BTEX and
      biphenyl by this strain is linked to a catabolic pathway with overlapping
      specificities. The broad substrate specificity of these environmental isolates
      has important implications for bioremediation efforts in the field.

PMID- 10919339
TI  - Denitrification with methane as electron donor in oxygen-limited bioreactors.
AB  - The microbial population from a reactor using methane as electron donor for
      denitrification under microaerophilic conditions was analyzed. High numbers of
      aerobic methanotrophic bacteria (3 10(7) cells/ml) and high numbers of acetate
      utilizing denitrifying bacteria (2 10(7) cells/ml) were detected, but only very
      low numbers of methanol-degrading denitrifying bacteria (4 10(4) cells/ml) were
      counted. Two abundant acetate-degrading denitrifiers were isolated which, based
      on 16S rRNA analysis, were closely related to Mesorhizobium plurifarium (98.4%
      sequence similarity) and a Stenotrophomonas sp. (99.1% sequence similarity). A
      methanol-degrading denitrifying bacterium isolated from the bioreactor
      morphologically resembled Hyphomicrobium sp. and was moderately related to H.
      vulgare (93.5% sequence similarity). The initial characterization of the most
      abundant methanotrophic bacterium indicated that it belongs to class II of the
      methanotrophs. "In vivo" 13C-NMR with concentrated cell suspensions showed that
      this methanotroph produced acetate under oxygen limitation. The microbial
      composition of reactor material together with the NMR experiments suggest that in
      the reactor methanotrophs excrete acetate, which serves as the direct electron
      donor for denitrification.

PMID- 10919340
TI  - Enalapril in RAPIDISC (wafer formulation): pharmacokinetic evaluation of a novel,
      convenient formulation.
AB  - BACKGROUND: Enalapril in RAPIDISC* (wafer), a new easy-to-administer formulation
      of enalapril, may improve the convenience of enalapril therapy, thereby helping
      patients adhere to antihypertensive treatment. SUBJECTS AND METHODS: To determine
      whether 20 mg enalapril wafer is bioequivalent to the conventional 20 mg
      enalapril tablet, an open-label, two-period crossover study was performed in 16
      healthy male volunteers. Cumulative urinary recovery of free enalaprilat (active
      metabolite of enalapril) and the serum maximum concentration of free enalaprilat
      (Cmax) were the primary pharmacokinetic parameters used to determine
      bioequivalence in this study. Bioequivalence was defined as the geometric mean
      ratio (wafer: tablet) falling within the equivalence limits of 0.80 to 1.25 for
      both parameters. RESULTS: Cumulative urinary recovery of free enalaprilat (0 - 72
      hours) was similar between the wafer and conventional tablet formulations
      (arithmetic mean 5.13 vs. 5.03 mg, about 36% of dose). The geometric mean ratio
      of the urinary recovery of free enalaprilat (wafer: tablet) was 1.03 (90% CI:
      0.93, 1.15). Cmax of serum enalaprilat was also similar between the wafer and
      conventional tablet formulations (arithmetic mean 85.7 vs. 76.3 ng/ml). The
      geometric mean Cmax ratio (wafer: tablet) was 1. 10 (90% CI: 1.00, 1.22). Both
      enalapril formulations were well tolerated. CONCLUSION: This study demonstrates
      that 20 mg enalapril in RAPIDISC is bioequivalent to 20 mg enalapril conventional
      tablet.

PMID- 10919341
TI  - Pharmacokinetic consideration on administration regimen of lamivudine in japanese
      patients infected with HIV-1.
AB  - OBJECTIVE: The typical regimen for lamivudine is 150 mg bis in die (bid).
      However, pharmacokinetic values of lamivudine will differ among individual
      patients. In addition, few studies regarding the pharmacokinetics of lamivudine
      in the Japanese people have so far been reported. Therefore, we have aimed to
      examine the variation in the pharmacokinetic values of lamiduvine present in six
      Japanese patients with HIV-1 infection. PATIENTS AND METHODS: Lamivudine
      concentrations were measured in three hemophiliacs (HIV-1-asymptomatic carrier,
      AC) and three non-hemophiliacs (2 of these patients were AC and one had AIDS
      related complex, ARC). In order to simulate the lamivudine plasma concentrations
      found in chronic oral administration, we added an absorption compartment to the
      two-compartment model. RESULTS: The mean +/- SD of Tmax, Cmax, AUC(0 - infinity)
      and t1/2beta were 1.2 +/- 0.5 (hours), 1,280 +/- 267 (ng/ml), 6,778 +/- 2,763 (ng
      x h/ml), and 10.3 +/- 4.7 (hours), respectively. Although these values were
      comparable on average to those previously reported, there were noticeable
      differences with respect to the various time courses of drug plasma concentration
      among each patient. CONCLUSION: Computations speculated that the trough and peak
      plasma concentrations as well as the AUC at steady-state change significantly
      depending on each patient. It suggests that individual pharmacokinetic values of
      lamivudine should be determined before deciding the optimal administration dose
      for specific patients.

PMID- 10919342
TI  - Butyrylcholinesterase and C5+ variant in a Javanese ethnic group in Indonesia.
AB  - OBJECTIVE: This study was designed to investigate the butyrylcholinesterase
      (BChE) and C5 variant phenotypes in a Javanese ethnic group in Indonesia. BLOOD
      DONORS, MATERIALS AND METHODS: Random blood samples from a Javanese ethnic group
      were obtained from the Indonesian Red Cross Service. The donors were 40.09 +/-
      9.53 years old, consisting of 358 (89.45%) males and 42 females (10.55%). The
      plasma content of BChE was determined spectrophotometrically using benzoylcholine
      as substrate, and phenotyping of BChE was performed using the inhibitors 10
      microM dibucaine and 50 microM sodium fluoride. Phenotyping of the C5+ variant
      was carried out by means of polyacrylamide gel electrophoresis using a 7.5% (w/v)
      acrylamide slab gel and a 3% (w/v) acrylamide stacking gel, and stained with fast
      red azo dye. RESULTS: The results show that of 398 samples studied, the average
      activities of BChE are 1.00 +/- 0.22 U/ml. 377 individuals (94.72%) show normal
      activities, whereas 21 individuals (5.78%) are below normal (< 0.690 U/ml). The
      mean +/- SD of dibucaine number (DN) is 83 +/- 5 and the fluoride number (FN) is
      66 +/- 6. From this population we identified one individual with UA phenotype
      (total activity: 0.310 U/ml, DN: 62, and FN: 50). The frequency of C5+ variant in
      the population as detected by acrylamide electrophoresis is 21%. CONCLUSION: Our
      data indicate that the atypical allele of BChE is rare and that the C5+ variant
      is detected in high frequency in the ethnic Javanese of Indonesia.

PMID- 10919343
TI  - Clarithromycin bioequivalence study of two oral formulations in healthy human
      volunteers.
AB  - OBJECTIVE: To assess the bioequivalence of two tablet formulations of
      clarithromycin (Clamicin 500 mg from Medley Indlistria Farmaceutica, Brazil, as
      the test formulation, and Biaxin 500 mg from Abbott Industries, USA, as the
      reference formulation). METHODS: A single 500 mg oral dose of each formulation
      was administrated in 24 healthy volunteers of both sexes (12 males and 12
      females). The study was conducted open, randomized, two-period crossover design
      with a 7-day interval between doses. The plasma concentrations of clarithromycin
      were quantified by reversed phase liquid chromatography coupled to tandem mass
      spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple
      reaction monitoring (MRM) method. 14-hydroxyclarithromycin concentration was
      estimated semiquantitatively as equivalent of clarithromycin/ml. The precision of
      the method was evaluated using calibration curves and plasma quality control
      samples. The pharmacokinetic parameters calculated for both compounds included:
      AUC(0 - 48h), AUC(0 - infinity), Cmax, Cmax/AUC(0 - 48h), Tmax, T1/2 and Ke.
      RESULTS: Standard curves of clarithromycin in plasma were linear in the range of
      0.05 microg x ml(-1) to 10 microg x ml(-1) (r > 0.999). The limit of
      quantification was 5 ng/ml. Within- and between-run plasma quality control CV
      were 5.8% and 15.7%, respectively. Inaccuracy within- and between-runs were 14%
      and 17%, respectively. 90% CI for clarithromycin geometric mean AUC(0 - 48h),
      AUC(0 - infinity) and Cmax ratios (test/reference) were: 8.7% - 103.1%, 89.4% -
      103.7% and 85.4% - 99.6%, respectively, and for hydroxyclarithomycin were 80.3% -
      108.6%, 80.1% - 110.1% and 85.4% - 112.6%, respectively. CONCLUSION: The method
      described for the quantification of charithomycin and its main metabolite is
      accurate and sensitive. Clamicin was considered bio-equivalent to Biaxin based on
      the rate and extent of absorption. Since these were no significant differences in
      the bioequivalence determined using the pharmacokinetic parameters of either
      clarithromycin or 14-hydroxyclarithromycin, we suggest that future bioequivalence
      trials of this drug may be performed by quantifying clarithromycin only.

PMID- 10919344
TI  - Pharmacokinetics and bioequivalence testing of generic fluconazole preparations
      in healthy thai volunteers.
AB  - AIM: To determine the bioequivalence of two oral formulations of generic
      fluconazole in twelve healthy Thai volunteers. SUBJECTS, MATERIALS AND METHODS:
      The test preparation was Flucozole (Siam Bheasach, Thailand) and the reference
      was Diflucan (Pfizer Inc.). The two products were administered as 200 mg single
      oral doses in a two-period crossover design with a two-week washout period. After
      drug administration, serial blood samples were collected over a period of 72
      hours. Serum fluconazole concentrations were determined by HPLC, and the
      pharmacokinetic parameters were analyzed by non-compartmental analysis. RESULTS:
      The time to reach the maximal concentration (Tmax, hour) of Flucozole (1.18 +/-
      0.56) was statistically faster than that of Diflulan (1.59 +/- 0.54). The 90%
      confidence intervals of the AUC(0 - infinity) ratio and the Cmax, ratio muT/muR
      for Flucozole/Diflucan were 0.97 - 1.20 and 1.01 - 1.26, respectively. These
      values were within the acceptable bioequivalence intervals of 0.80 - 1.25 and 0.7
      - 1.43 for the ratio of the average AUC(0 - infinity) and Cmax, respectively.
      CONCLUSION: Thus, our study demonstrated the bioequivalence of Flucozole and
      Diflucan with respect to the rate (Cmax) and extent of absorption (AUC(0 -
      infinity).

PMID- 10919345
TI  - Anosmia induced with alpha interferon in a patient with chronic hepatitis C.
AB  - This is a report of the alpha interferon-induced acute anosmia in a 37-year old
      patient with chronic hepatitis C. This exceptionally rare side-effect started in
      our patient as a smelling problem 2 weeks after the initiation of the therapy,
      and anosmia is still present 13 months after the discontinuation of the alpha
      interferon. We presume that neurotoxic mechanism could be responsible for this
      side-effect.

PMID- 10919346
TI  - Effect of omega-3 fatty acids in the management of fibromyalgia syndrome.

PMID- 10919347
TI  - Aggregation of alpha-synuclein/NACP in the neuronal and glial cells in diffuse
      Lewy body disease: a survey of six patients.
AB  - BACKGROUND: alpha-Synuclein is now known to be a major component of Lewy bodies
      (LBs) in Parkinson's disease (PD) and diffuse Lewy body disease (DLBD). Recently,
      cytoplasmic aggregation of alpha-synuclein has also been reported to occur in
      glial cells in these diseases. METHODS: We have conducted an immunohistochemical
      survey to clarify in detail the distribution of alpha-synuclein aggregates in the
      central nervous system of patients with DLBD. The cerebrum, brainstem, cerebellum
      and spinal cord of six patients with DLBD were examined immunohistochemically
      using anti-alpha-synuclein antibodies. RESULTS: In all patients, alpha-synuclein
      immunoreactive cytoplasmic inclusions, including those with profiles of typical
      LBs, were visualized in neurons of the cerebral neocortex, hippocampus,
      amygdaloid nucleus, hypothalamus, brainstem pigmented nuclei and reticular
      formation. In some of these patients, similar spherical cytoplasmic inclusions
      were also detected in neurons of the olfactory bulb, basal ganglia, thalamus, the
      subthalamic, pontine, inferior olivary and cerebellar dentate nuclei, and in the
      spinal gray matter. Moreover, alpha-synuclein-immunoreactive cytoplasmic
      inclusions, which appeared circular or coil-like in shape, were found in glial
      cells. In four patients with longstanding DLBD, these cytoplasmic inclusions were
      distributed widely in brain areas, including brainstem, basal ganglia, and
      cerebral and cerebellar white matter. CONCLUSION: The widespread occurrence of
      alpha-synuclein aggregates in both neuronal and glial cells is a pathological
      feature in patients suffering from DLBD.

PMID- 10919348
TI  - Cerebral granular cell astrocytomas: a Mib-1, bcl-2, and telomerase study.
AB  - Granular cell (GC) astrocytoma is an uncommon variant of glioma that shares the
      cytologic features and high cytoplasmic lysosomal content with granular cell
      tumors elsewhere in the body. While the histogenesis and behavior of these
      neoplasms was originally in dispute because most were reported as single cases,
      the accumulated literature on approximately three dozen such lesions has now
      verified their usual astrocytic lineage and poor prognosis. Although the GC cell
      is thought to represent a degenerative process, little is known in these tumors
      about cell cycle regulation, as measured by Mib-1 and bcl-2 immunolabeling, or
      expression of other biomarkers of malignancy, such as telomerase. In our study,
      GC astrocytomas were similar to gemistocytic astrocytomas in their bland
      histology, often prominent perivascular lymphocytic cuffing and low Mib-1
      labeling indices. Like gemistocytes, GCs appear to represent senescent, non
      cycling cells. Absence of significant bcl-2 immunolabeling in our three cases,
      however, suggests that unlike gemistocytes, GC astrocytes develop senescence by
      mechanisms other than bcl-2 mediated apoptosis suppression. In one case in which
      frozen tissue was available for assay, we noted relatively high quantitative
      telomerase expression. The level paralleled that seen in other glioblastomas.
      Demise for our three patients occurred 3-25 months post-biopsy. Like
      gemistocytes, the presence of non-proliferative GCs signifies severe
      abnormalities in cell cycle regulation and maybe hallmarks of tumors with poor
      prognosis.

PMID- 10919349
TI  - Astrocytoma with angiomatoid vascular proliferation ("angiomatous astrocytoma").
AB  - We report a surgical case of unusual anaplastic astrocytoma which was accompanied
      by an exuberant proliferation of abnormal blood vessels with features resembling
      those of capillary telangiectasis or cavernous angioma. The patient was a 39-year
      old man, who presented with a generalized convulsive seizure, and
      neuroradiological examination revealed a tumor in the left frontal lobe. The
      resected tumor showed the features of an anaplastic astrocytoma, grade 3. The
      proliferation of abnormal blood vessels with dilated lumina and thin walls was
      seen throughout the tumor, and in the central area these vessels were densely
      packed and almost replaced the neoplastic astrocytic tissue. Although these dense
      vascular aggregates in the central area closely simulated capillary
      telangiectasis or cavernous angioma, they were considered to be of a reactive
      nature. The term "angiomatous astrocytoma", which is analogous to angiomatous
      meningioma, seemed to be the most appropriate for the present tumor.

PMID- 10919350
TI  - Supratentorial desmoplastic ependymoma with giant ependymal rosettes.
AB  - We report a case of a 22-year-old female who presented with a solid tumor in the
      frontal lobe having no continuity with the wall of the lateral ventricle. The
      tumor was excised. The patient has been free from clinical symptoms and tumor
      recurrence for over nine years. Microscopically, the tumor was composed of
      extremely large ependymal true rosettes, resembling medulloepithelioma, and thick
      fibrous septa, which were surrounded by thick reactive gliosis. There were no
      histological signs of malignancy. In our case, the tumor is assumed to be a
      variant of gliofibroma for which we propose the term "desmoplastic ependymoma".

PMID- 10919351
TI  - Corticobasal degeneration: an autopsy case clinically diagnosed as progressive
      supranuclear palsy.
AB  - We report an autopsy case diagnosed clinically as progressive supranuclear palsy
      (PSP), but neuropathologically confirmed as corticobasal degeneration (CBD). A 56
      year-old Japanese woman slowly developed parkinsonism, dementia, character
      change, followed by vertical gaze palsy and dystonia. Brain MRI demonstrated
      diffuse cerebral atrophy with severe shrinkage of the brain stem tegmentum. The
      SPECT images using 123I-IMP disclosed symmetrical hypoperfusion in the frontal
      lobes. She died of respiratory failure at the age of 71. Gross inspection of the
      brain showed diffuse, symmetrical atrophy of the cerebrum and marked atrophy of
      the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem
      tegmentum. Microscopically, neuronal loss and fibrillary gliosis were observed in
      the Luysian body, globus pallidus, substantia nigra and nuclei of the brain stem
      tegmentum. The cerebellar dentate nucleus showed mild neuronal loss with some
      grumose degeneration. Neurofibrillary tangles were found only in the Luysian
      body, substantia nigra and raphe nuclei, whilst tau-positive inclusions were
      observed more extensively. Astrocytic plaques and swollen achromatic neurones
      were found in the postcentral gyrus. There were no tuft-shaped astrocytes in the
      brain. The clinicopathological similarities and differences between PSP and CBD
      are discussed.

PMID- 10919352
TI  - Immunohistochemical demonstration of spinal ventral horn cells involvement in a
      case of "myoclonus epilepsy with ragged red fibers" (MERRF).
AB  - OBJECTIVE: To detect mitochondrial lesions in the spinal cord from an autoptic
      case of myoclonus epilepsy with ragged-red fibers (MERRF) that harbored the
      A8344G mutation and was deemed to be free of pathological abnormalities in the
      spinal cord after conventional post-mortem examination. MATERIALS AND METHODS:
      Antibodies against subunits of complex III and IV of the respiratory chain were
      used to perform immunohistochemical analysis on cervical, thoracic and lumbar
      sections of the spinal cord from the case of MERRF and from controls.
      Immunostaining was carried out by the avidin-biotin peroxidase complex (ABC)
      method. RESULTS: A selective decreased expression of subunit II of cytochrome c
      oxidase (COX-II) was found in all spinal cord sections from the patient.
      CONCLUSIONS: The immunohistochemical demonstration of mitochondrial lesions in
      the spinal ventral horn cells from this case with MERRF seems to be consistent
      with the results of many genetic studies pointing to a high and homogeneous
      distribution of mutant mtDNA in different neuronal populations of patients with
      this disease. The use of these immunological probes in the study of mitochondrial
      encephalomyopathies can increase both the resolution and the specificity of
      morphological observations in the central nervous system (CNS).

PMID- 10919353
TI  - A sporadic, atypical case of desminopathy: morphological and immunological
      characterization.
AB  - Recently, abnormal expression of cyclin-dependent kinases was proposed as a
      possible cause of desminopathy. We describe an atypical case clinically
      characterized by severe respiratory distress. Muscle biopsy showed subsarcolemmal
      and intracytoplasmic accumulation areas, which intensively stained with anti
      desmin antibodies and contained electrondense filamentous material at
      ultrastructural level. WB analysis showed 30% increased desmin signal compared to
      controls. Positive immunostain for CDC2 kinase, CDK2 and emerin and nuclear
      matrix-associated protein were, found in desmin-positive fibres.

PMID- 10919354
TI  - In vivo targeting by liposomes.
AB  - This review deals with the current status of newly developed pendant-type PEG
      immunoliposomes (Type C), carrying monoclonal antibodies or their fragments
      (Fab') at the distal ends of the PEG chains. In terms of target binding of Type
      C, two different anatomical compartments are considered. They are mouse lung
      endothelium as a readily accessible site via the intravascular route and the
      implanted solid tumor as a much less accessible target site reached via
      extravasation. Distearoyl phosphatidylethanolamine derivatives of PEG with a
      carboxyl group (DSPE-PEG-COOH) and dipalmitoyl phosphatidylethanolamine
      derivatives of PEG with a maleimidyl group (DPPE-PEG-Mal) at the PEG terminus
      were newly synthesized. Small unilamellar liposomes (90-130 nm in diameter) were
      prepared from phosphatidylcholine and cholesterol (2 : 1, m/m) containing 6 mol%
      of DSPE-PEG-COOH or DPPE-PEG-Mal. For targeting to the vascular endothelial
      surface in the lung, 34A antibody, which is highly specific to mouse pulmonary
      endothelial cells, was conjugated to PEG-liposomes (34A-Type C). The degree of
      lung binding of 34A-Type C in BALB/c mouse was significantly higher than that of
      34A-Type A, which is an ordinary type of immunoliposome (without PEG
      derivatives). For targeting to solid tumor tissue, 21B2 antibody (anti-human CEA)
      and its Fab' fragment were used. The targeting ability of Fab'-Type C was
      examined by using CEA-positive human gastric cancer strain MKN-45 cells
      inoculated into BALB/c nu/nu mice. Fab'-Type C showed low RES uptake and a long
      circulation time, and enhanced accumulation of the liposomes in the solid tumor
      was seen. The small Fab'-Type C predominantly passed through the leaky tumor
      endothelium by passive convective transport. These studies offer important
      insights into the potential of Type C liposomes for target-specific drug
      delivery.

PMID- 10919355
TI  - Relationship of two ribonucleases with molecular masses of 45 kDa and 37 kDa from
      the culture medium of Lentinus edodes.
AB  - Lentinus edodes (shiitake) produces three base non- specific and acid
      ribonucleases, RNase Le2, RNase Le37 and RNase Le45. The primary structures of
      the former two RNases, having molecular masses about 24 and 37 kDa, respectively,
      have been elucidated to be members of the RNase T2 family. The latter two are
      excreted from mycelia into the medium. In this report, we estimated the primary
      structure of RNase Le45 using the following experimental evidence. (i) The
      partial amino acid sequence of RNase Le45 determined that up to about 60% of
      total protein was identical with that of RNase Le37. (ii) The amino acid
      composition of RNase Le45 was identical to that of RNase Le37. (iii) The elution
      profiles on HPLC of lysylendopeptidase and Staphylococcus aureus V8 protease
      digests of RCM-RNase Le45 (reduced and S-carboxymethylated RNase Le45) were very
      similar to those of RNase Le37, except for the absence of C-terminus peptide
      which contained O-glycosylated peptides. However, RNase Le45 contained about 70
      residues of mannose and 4 residues of hexosamine. These values were more than
      twice those of RNase Le37. (iv) RNase Le45 was immunologically indistinguishable
      from RNase Le37. (v) After treatment with both glycosidase EndoH and alpha
      mannosidase, RNases Le37 and Le45 gave complex bands by slab-gel electrophoresis.
      However, one of the major bands with the highest mobility from RNase Le45 and
      Le37 showed the molecular mass of 29 kDa in common, which is slightly larger than
      that of RNase Le2 containing no carbohydrate. These results indicated that RNase
      Le45 is an enzyme which is a heavily glycosylated species of RNase Le37.

PMID- 10919356
TI  - Lysosomal cysteine protease, cathepsin H, is targeted to lysosomes by the mannose
      6-phosphate-independent system in rat hepatocytes.
AB  - The contribution of mannose 6-phosphate (Man 6-P)-dependent and -independent
      systems to lysosomal targeting of cathepsin H, a lysosomal cysteine protease, was
      investigated by metabolic labeling with [32P]phosphate and
      [35S]methionine/cysteine in primary cultures of rat hepatocytes. Metabolic
      labeling experiments with [32]phosphate revealed that only the proform of
      cathepsin H acquired Man 6-P residues on its high mannose type oligosaccharide,
      and that most of the phosphorylated procathepsin H was secreted into the medium
      without having undergone significant intracellular dephosphorylation. Thus,
      acquisition of Man 6-P residues did not correlate with targeting of cathepsin H
      to lysosomes. Pulse-chase experiments with [35S]methionine/cysteine showed that
      only about 10% of the newly synthesized cathepsin H was secreted as a proform
      while the remainder was retained intracellularly in processed mature form. These
      results indicate that the majority of newly synthesized cathepsin H is targeted
      to lysosomes by a Man 6-P-independent mechanism, at least in rat hepatocytes.

PMID- 10919357
TI  - Sulfotransferases in a human colon carcinoma cell line, Caco-2.
AB  - We investigated the expression of sulfotransferases (STs) in the human colon
      carcinoma cell line, Caco-2, which is widely used as a human intestine model for
      orally administered drugs. By reverse transcription-polymerase chain reaction (RT
      PCR), we could detect mRNA expressions of phenol STs (P-ST), hydroxysteroid ST
      (HS-ST) and estrogen ST (E-ST). Treatment with 1,25-dihydroxyvitamine D3, which
      induces CYP3A4 expression in Caco-2 cells, did not affect the ST expression of
      the cells. We detected significant P-ST activity toward 2-naphthol and dopamine
      in the cell extract. We also observed detectable HS-ST activity toward
      dehydroepiandrosterone (DHEA), but no E-ST activity toward beta-estradiol was
      observed in the extract. Analyses by RT-PCR and separation of P-ST activities on
      ion-exchange column chromatography showed that the thermolabile monoamine phenol
      sulfotransferase (M-PST) is dominant in Caco-2 cells.

PMID- 10919358
TI  - Transcriptional induction of Nur77 by indomethacin that results in apoptosis of
      colon cancer cells.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) have cancer preventive and tumor
      regressive effects in the human colon, perhaps due to their capability to induce
      apoptosis of the colon cancer cells. Here, we report that indomethacin induced
      the expression of Nur77 which has been implicated in activation-induced apoptosis
      of T-lymphocytes, in a colon cancer cell line, HCT-15. The transcript- and
      protein-level, the transcriptional activity of Nur77 promoter, and the DNA
      binding of Nur77 were significantly induced following indomethacin treatment.
      Among the two potential trans-acting factors that activate Nur77-promoter,
      indomethacin induced DNA binding and reporter gene activity of AP-1, but not that
      of related serum response factor (RSRF), suggesting that the transcriptional
      induction of Nur77 may be mediated through activation of AP-I. Further, we showed
      that all trans-RA repressed the induction of Nur77 as well as the apoptosis
      induced by indomethacin, providing evidence that transcriptional induction of
      Nur77 may be an important mechanism by which indomethacin induces apoptosis in
      colon cancer cells.

PMID- 10919359
TI  - Effects of SA7060, a novel dual inhibitor of neutral endopeptidase and
      angiotensin-converting enzyme, on deoxycorticosterone acetate-salt-induced
      hypertension in rats.
AB  - We evaluated whether a novel dual inhibitor of neutral endopeptidase (NEP) and
      angiotensin-converting enzyme (ACE), SA7060, (S)-2-[3-[(S)-2-(butoxycarbonyl)-2
      hydroxyethyl]-3-isobutylureido] -3-(2-naphtyl) propionic acid, prevents
      deoxycorticosterone acetate (DOCA)-salt-induced hypertension and related organ
      damage, such as cardiovascular hypertrophy, renal dysfunction and renal tissue
      injury in rats. The effectiveness was compared with candoxatril and enalapril,
      which are a selective NEP and ACE inhibitor, respectively. During DOCA-salt
      treatment for 4 weeks, the rats were given SA7060, candoxatril, enalapril or
      vehicle, once daily by gavage. The 4-weeks treatment with DOCA and salt produced
      progressive increases in systolic blood pressure. Daily administration of SA7060,
      candoxatril or enalapril significantly suppressed the development of hypertension
      induced by DOCA and salt, although the effect of enalapril was less potent at 4
      weeks of the treatment period. In vehicle-treated DOCA-salt rats, decreases in
      creatinine clearance and increases in urinary excretion of protein and blood urea
      nitrogen were observed. This functional damage was improved most efficiently by
      the treatment with SA7060. There were significant increases in urinary excretions
      of atrial natriuretic peptide and cyclic GMP in SA7060- or candoxatril-treated
      animals. Histopathological examination of the kidney in DOCA-salt rats revealed
      tubular, glomerular and vascular lesions, all of which were improved in animals
      given SA7060 or candoxatril. When the vascular hypertrophy of the aorta was
      evaluated, there were significant increases in wall thickness, wall area and the
      wall-to-lumen ratio in vehicle-treated DOCA-salt rats compared with the sham
      rats. The development of vascular hypertrophy was suppressed by the treatment
      with SA7060, candoxatril or enalapril. Our findings indicate that SA7060
      efficiently prevents DOCA-salt-induced hypertension and related tissue injury,
      mainly by inhibiting NEP. Thus, SA7060 may be useful for treatment of both renin
      dependent and renin-independent hypertensive subjects, although further studies
      examining efficiency in a renin-dependent hypertensive model are needed.

PMID- 10919360
TI  - Inducible nitric oxide synthase mRNA is upregulated in skin tumors of v-ha-ras
      transgenic TG-AC mice treated with 12-o-tetradecanoylphorbol-13-acetate.
AB  - The correlation between the steady-state level of inducible nitric oxide synthase
      (iNOS) mRNA and skin tumors induced following treatment with 12-o
      tetradecanoylphorbol-13-acetate (TPA) was investigated in transgenic TG-AC mice,
      which carry the v-Ha-ras oncogene fused to the promoter of the mouse embryonic
      alpha-like, zeta-globin gene. In animals treated with TPA (2.5 microg x 2/week,
      for 2 weeks), the increase of iNOS mRNA was locally confined only to the regions
      of papillomas, but not to the skin tissues surrounding the papillomas. However,
      the tissues surrounding the papillomas showed only a minor increase in the steady
      state level of iNOS mRNA. These data suggest that iNOS gene expressions may
      underlie tumorigenesis during TPA promotion in TG-AC mice.

PMID- 10919361
TI  - Metabolism of rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside from the
      rhizome of rheum undulatum by human intestinal bacteria and their anti-allergic
      actions.
AB  - Rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside isolated from the
      rhizomes of Rheum undulatum (Family Polygonaceae) are metabolized to
      rhapontigenin and chrysophanol, respectively, by human intestinal microflora.
      Most intestinal bacteria isolated from human feces catalyzed these metabolic
      pathways. Among rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside and their
      metabolites, rhapontigenin had the most potent inhibitory activity on a
      hyaluronidase, a histamine release from mast cell and passive cutaneous
      anaphylaxis (PCA) PCA reaction. The inhibitory activity of rhapontigenin was more
      potent than that of disodium cromoglycate, one of the commercial anti-allergic
      drugs. These results suggest that rhaponticin in the rhizomes of R. undulatum is
      a prodrug that has an extensive anti-allergic property.

PMID- 10919362
TI  - Immunostimulatory effects of cycloartane-type triterpene glycosides from
      astragalus species.
AB  - In the course of our research on the oligoglycosidic constituents of Turkish
      Astragalus species, we have isolated a number of cycloartane-type triterpene
      glycosides. The current study examines the immunostimulatory effects of nineteen
      of these cycloartane-type compounds using a transcription-based bioassay for
      Nuclear Factor kappa B (NF-kappaB) activation in a human macrophage/monocyte cell
      line, THP-1. All compounds were inactive at 100 microg/ml except astragaloside I
      which increased NF-kappaB directed luciferase expression to levels about 65% as
      compared with maximal stimulation by E. coli lipopolysaccharide (LPS) at 10
      microg/ml. None of the compounds were active at low dosage levels (0.1 microg/ml)
      in combination with 50 ng/ml LPS. Astragaloside I also increased mRNA expression
      of the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis
      factor-alpha (TNF-alpha) as measured using reverse transcriptase-polymerase chain
      reaction (RT)-PCR. Based on these results it is clear that certain structural
      features are required for immunostimulation of cycloartane-type triterpene
      glycosides.

PMID- 10919364
TI  - Percutaneous penetration of ozagrel and the enhancement produced by saturated
      fatty acids.
AB  - The effects of a series of fatty acids on the percutaneous penetration of ozagrel
      (OZ), a selective thromboxane A2 synthetase inhibitor, through rat skin and the
      mechanism by which fatty acids enhance the skin penetration of OZ were examined
      in vitro. Lauric acid, at the fatty acid: OZ molar ratio of 2 : 1, was the most
      potent agent as far as increasing the skin penetration was concerned, with a flux
      24-fold higher than that without fatty acid. A molar ratio of 3 : 1 also produced
      a large enhancing effect, comparable with that of a molar ratio of 2 : 1. When
      the gel formulation with lauric acid (molar ratio of 2 : 1) was applied to the
      skin for 6 h, the amount of drug penetrating into the skin was significantly
      increased compared with that after the formulations without lauric acid and with
      capric and palmitic acids. However, lauric acid did not change the apparent
      partition coefficient of OZ between n-heptane and phosphate buffer (pH 7.4). The
      13C-NMR spectra of OZ was also unaffected by the addition of lauric acid,
      indicating that a complex or ion pair with lauric acid was not formed. A possible
      mechanism for the enhancing effect is the increased incorporation of lauric acid
      with OZ into the bulk lipid phase of the stratum corneum, where the fatty acid
      would act as a co-penetrant enhancing passage through the stratum corneum.

PMID- 10919363
TI  - Evaluation of absorbability of poorly water-soluble drugs: validity of the use of
      additives.
AB  - Apparent membrane permeation coefficients (Papp) of poorly water-soluble drugs
      such as indomethacin (IDM) and triamterene (TAT) were obtained by the chamber
      method using an isolated rat intestinal tissue after solubilization of the drugs
      by additives. For the additives, sodium deoxycholate (DOC), polyethylene glycol
      600 (PEG 600), dimethylsulfoxide (DMSO), ethanol (EtOH), propylene glycol (PG),
      and rat bile were examined. Their concentrations were determined in ranges
      considered to be appropriate from the results of in vivo experiments and
      physiological findings. From the correspondence between this membrane
      permeability and in vivo bioavailability, we evaluated the validity of our in
      vitro experiment. On the basis of these evaluations, it was shown that 5% DMSO
      and 10% PEG 600, which did not affect the membrane integrity, were most
      appropriate additives for chamber experiments. Papp of IDM was greater than that
      of TAT, indicating that the order corresponded with that of in vivo
      bioavailability after oral administration of their PEG 600 solutions.
      Accordingly, it was concluded that Papp obtained by our in vitro system can be
      used to assess the in vivo bioavailability.

PMID- 10919366
TI  - In situ and in vitro evidence for stereoselective and carrier-mediated transport
      of monocarboxylic acids across intestinal epithelial tissue.
AB  - The present study was designed to establish the significance of carrier-mediated
      transport in the intestinal absorption of monocarboxylic acids by examining the
      stereoselectivity of transepithelial transport of chiral monocarboxylic acids.
      The transport of L- and D-lactic acids was examined in vitro using rat intestinal
      tissue sheets and in situ by means of intra-jejunal administration, followed by
      measurement of the plasma concentration. Both the absorptive and secretory
      transport of L-[14C]lactic acid across the intestinal epithelial tissues of rats
      was significantly greater than that of the D-isomer. The secretory transport of
      the L-isomer was significantly greater than the absorptive transport, implying
      net transport in the secretory direction. When L- and D-[14C]lactic acids were
      administered to the rat jejunum, the absorption ratio of the L-isomer was lower
      than that of the D-isomer at 15 min after administration. The concentration
      dependence of absorption for both L- and D-[14C]lactic acids indicated the
      involvement of both saturable and nonsaturable processes. The saturable process
      showed a higher affinity and lower capacity for L-lactic acid compared with the D
      isomer, while no significant difference between the isomers was observed in the
      nonsaturable process. The absorption of L-lactic acid was inhibited by chiral 2
      hydroxymonocarboxylic acids in a stereoselective manner. Chiral monocarboxylic
      acids were shown to cross the intestinal epithelial tissues and to be absorbed in
      a stereoselective manner after oral administration, suggesting the involvement of
      specific carrier-mediated transport mechanism(s) in their intestinal absorption
      in vivo.

PMID- 10919365
TI  - Use of electroporation to accelerate the skin permeability enhancing action of
      oleic acid.
AB  - Rat skin permeability after treatment by electroporation (newly developed frog
      type electrode, 100V, 10 pulses), oleic acid/propylene glycol (PG) and a
      combination of both were investigated using Fourier transformed infrared
      attenuated total reflectance (FT-IR/ATR) analysis. Electroporation immediately
      disordered the stratum corneum lipid structure up to a certain threshold level.
      This action lasted throughout the experiment. This may be attributed to the
      formation of long lifetime of metastable lipid structures, which may allow
      molecules to pass to the inside of the stratum corneum due to the electroporation
      induced fluidized lipid membranes. Electroporation also altered the protein
      structure of the stratum corneum. When electroporation was combined with 0.05 M
      oleic acid/PG, uptake of oleic acid and PG into the stratum corneum was
      remarkably accelerated compared to the application of only 0.05 M oleic acid/PG
      to the skin. This indicates that electroporation enables oleic acid and PG to
      penetrate the stratum corneum easily by disrupting the structure of the latter.
      PG transfer into the dermis from the epidermis was accelerated, not because of
      the direct action of electroporation on the dermis, but because electroporation
      induced the rapidly disordering action of oleic acid on the stratum corneum.
      Lipid-soluble indomethacin permeated the skin more rapidly when the skin was
      treated with electroporation plus oleic acid/PG than with 0.05 M oleic acid/PG in
      vitro.

PMID- 10919367
TI  - Drug targeting efficacy to underlying muscle following topical application. I.
      Evaluation based on a physiological pharmacokinetic model.
AB  - A physiological pharmacokinetic model describing the absorption and disposition
      of topically applied drugs was proposed, and the effect of various
      pharmacokinetic and physiological parameters on the drug delivery into the
      targeted muscle was simulated. The proposed model consists of vehicle, and
      stratum corneum, viable epidermis and muscle below the application and reference
      sites, and plasma, each joined with transfer clearance and plasma flow.
      Indomethacin concentrations in tissues and plasma after topical application to
      rats could be explained by the model. Most indomethacin delivered into the
      underlying muscle was via direct penetration. The model simulation showed that
      the increase in plasma clearance and clearance between viable skin and muscle,
      and the decrease in application area and plasma flow rate into viable skin and
      muscle would promote the targeting efficacy of topically applied drugs to the
      underlying muscle.

PMID- 10919368
TI  - Antitumor 1,3-beta-glucan from cultured fruit body of Sparassis crispa.
AB  - Sparassis crispa is an edible mushroom recently cultivable in Japan.
      Polysaccharide fractions were prepared from the cultured S. crispa by repeated
      extraction with hot water (SCHWE), cold NaOH (SCCA), and then hot NaOH (SCHA).
      HWE was further separated by 1 volume (SCHWE1v) or 4 volumes (SCHWE4v) of ethanol
      precipitable fractions. By chemical, enzymic, and NMR analyses, the primary
      structures of SCHWE1v, SCCA, and SCHA were 6-branched 1,3-beta-glucan, having one
      branch in approximately every third mainchain unit. All of these fractions showed
      antitumor activity to the solid form of Sarcoma 180 in ICR mice with strong
      vascular dilation and hemorrhage reaction. These fractions also showed enhanced
      hematopoietic response to cyclophosphamide induced leukopenic mice following
      intraperitoneal or peroral administration.

PMID- 10919369
TI  - Inhibitory effects of fluvastatin and its metabolites on hydrogen peroxide
      induced oxidative destruction of hemin and low-density lipoprotein.
AB  - Some 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which
      are used as hypolipidemic drugs, have been reported to have the potential to
      reduce the oxidizability of plasma low-density lipoprotein (LDL) when they are
      administered in vivo. Their in vivo mechanism is believed to be closely related
      to their hypolipidemic action based on the HMG-CoA reductase inhibitory activity.
      We hypothesized that some type of HMG-CoA reductase inhibitor has additional
      mechanism inhibiting LDL oxidation in vivo due not to its hypolipidemic action
      but to its direct antioxidative effect based on its unique chemical structure. We
      directly compared in vitro the antioxidative effects of well-known HMG-CoA
      reductase inhibitors (fluvastatin, pravastatin, simvastatin, cerivastatin and
      atorvastatin) on the hydrogen peroxide-induced oxidative destruction of hemin and
      LDL. Fluvastatin but not the others showed the inhibitory effect on this system.
      Its effect was dose-dependent and almost as strong as the natural antioxidants,
      alpha-tocopherol and ascorbic acid. Further, M2, which is a hydroxylated
      metabolite of fluvastatin, showed stronger antioxidative activity than did
      fluvastatin. We suggest that among these HMG-CoA reductase inhibitors,
      fluvastatin especially has an ability to retard the LDL oxidation which is based
      on not only its hypolipidemic action but also its direct antioxidative effect.

PMID- 10919370
TI  - Properties and human origin of two angiotensin-I-converting enzyme inhibitory
      peptides isolated from a tryptic hydrolysate of human serum albumin.
AB  - Two angiotensin-I-converting enzyme (ACE) inhibitory peptides were isolated from
      a tryptic hydrolysate of human serum albumin (HSA). The peptides were identified
      by sequencing and other analyses as Ala-Trp and the nonapeptide Ala-Phe-Lys-Ala
      Trp-Ala-Val-Ala-Arg (human albutensin A), corresponding to f(213-214) and f(210-
      218) of HSA, respectively. Synthetic versions of both peptides had previously
      been shown to have ACE inhibitory activity. The present results are the first to
      show that these peptides have a potential natural origin in humans. Additional
      studies were done to define the inhibitory properties of these peptides, as they
      had not been previously reported. The dipeptide and nonapeptide showed dose
      dependent inhibition of ACE, with IC50 values of 12 and 1.7 micromol/l,
      respectively. Lineweaver-Burk plots suggested that Ala-Trp is a competitive
      inhibitor, and that human albutensin A is a noncompetitive inhibitor.

PMID- 10919371
TI  - Polyacetylenes from angelica gigas and their inhibitory activity on nitric oxide
      synthesis in activated macrophages.
AB  - In activated macrophages the inducible form of nitric oxide synthase (i-NOS)
      generates high amounts of the toxic mediator, nitric oxide (NO) which contributes
      to the circulatory failure associated with septic shock. Two polyacetylenes were
      isolated from the medicinal plant Angelica gigas and their structures were
      elucidated as octadeca-1,9-dien-4,6-diyn-3,8,18-triol (1) and 18-acetoxy-octadeca
      1,9-dien-4,6-diyn-3,8-diol (2) by spectroscopic method. These polyacetylenes and
      their peracetate, 3, 8, 18-triacetoxy-octadeca-1, 9-dien-4, 6-diyn (3) inhibited
      the production of NO in LPS-activated RAW 264.7 cells by suppressing the i-NOS
      enzyme expression. These new inhibitors of i-NOS expression may have potential in
      the treatment of endotoxemia and inflammation accompanied by the overproduction
      of NO.

PMID- 10919372
TI  - Anti-herpes virus activity of fabaceous triterpenoidal saponins').
AB  - Anti-herpes simplex virus type 1 (HSV-1) activity of oleanane-type triterpenoidal
      saponins obtained from some fabaceous plants were examined. Among sophoradiol
      glycosides, the order of potency was kaikasaponins III>I>>sophoradiol
      monoglucuronide. It was suggested that the trisaccharide group showed greater
      action than the disaccharide group. Neither the monoglucuronide of sophoradiol
      nor that of soyasapogenol B showed activity. Among the trisaccharide group of
      soyasapogenol B, the order of activity was azukisaponin V>soyasaponin
      II>astragaloside VIII>>soyasaponin I. Therefore, the saponin having a glucosyl
      unit in the central sugar moiety seemed to show greater action. In comparison
      with the activities for a group having the same trisaccharide, the potency of the
      sapogenol moieties was found to be in the order of soyasapogenol
      E>sophoradiol>>soyasapogenol B. Hence, the carbonyl group at C-22 would be more
      effective than the hydroxyl group in anti-HSV-1 activity, while the hydroxyl
      group at C-24 could reduce the activity.

PMID- 10919373
TI  - Nerve growth factor-potentiating compounds from Picrorhizae Rhizoma.
AB  - A crude methanol extract of Picrorhizae Rhizoma, the dried underground parts of
      Picrorhiza scrophulariiflora PENNELL, has been shown to potentiate the nerve
      growth factor (NGF)-induced neurite outgrowth from PC12D cells. The methanol
      extract was partitioned between ethyl acetate and water. The NGF-potentiating
      activity was observed in the ethyl acetate fraction. The ethyl acetate solubles
      were fractionated by silica gel chromatography, monitoring the NGF-potentiating
      activity to give two iridoid glycosides, picrosides I and II. Picrosides did not
      exhibit neurotrophic activity but caused a marked enhancement of the NGF-mediated
      neurite outgrowth from PC12D cells. The pharmacological data suggest that
      picrosides I and II enhance neurite outgrowth from PC12D cells, probably by
      amplifying a step in the NGF-receptor-mediated intracellular signaling pathway.

PMID- 10919374
TI  - Characterization of a binding site of UCN-01, a novel anticancer drug on alpha
      acid glycoprotein.
AB  - The binding site of 7-hydroxystaurosporine (UCN-01) on alpha-acid glycoprotein
      (AGP) was studied by fluorescence and ultracentrifugation experiments. Three
      ligands, propranolol, warfarin and progesterone were employed as marker ligands
      and quinaldine red was employed as a fluorescent probe. The presence of UCN-01,
      pro- pranolol, warfarin and progesterone resulted in a significant quenching of
      the fluorescence of quinaldine red, when bound to AGP, depending upon the potency
      of the binding to AGP. The construction of Klotz plots indicated that the
      displacement effects of propranolol, warfarin and progesterone on UCN-01-AGP
      binding were competitive in nature. These data suggest that the binding site of
      UCN-01 on the AGP partly overlaps the binding site for basic drugs, acidic drugs,
      as well as steroid hormones.

PMID- 10919375
TI  - pH regulation of gene expression in fungi.
AB  - A system for the regulation of gene expression by ambient (extracellular) pH was
      first identified in Aspergillus nidulans. This system consists of the products of
      the pacC and palA, B, C, F, H, and I genes. pacC encodes a zinc finger
      transcription factor and these pal genes encode components of an ambient pH
      signal transduction pathway. pH regulatory systems have also been identified in
      other fungi. Components of these regulatory systems are homologous to those in A.
      nidulans. This review describes the pH regulatory system in A. nidulans and the
      history of this research and how it relates to other systems. pH regulation in
      bacteria and animal cells is also briefly discussed.

PMID- 10919376
TI  - A genetic mosaic in the fruiting stage of Armillaria gallica.
AB  - The basidiome stage of Armillaria gallica can be a genetic mosaic. Ten cells
      isolated from a single basidiome in 1986 produced nine different genotypes when
      analyzed for variation at six nuclear loci. Four additional basidiomes collected
      in 1986 produced mosaic patterns when analyzed for variation at a single nuclear
      (PCR-RFLP) locus. One basidiome collected in 1993 was not a genetic mosaic
      because 15 cells isolated from it produced only one genotype when analyzed for
      six nuclear loci. Two hundred seventy-four samples collected in the field between
      1981 and 1998 were analyzed for variation at the PCR-RFLP locus. Samples
      collected prior to 1988 produced patterns consistent with the existence of
      mosaicism, but samples collected after 1988 showed no evidence of mosaicism.
      Genetic mosaicism represents a novel mechanism for partitioning genotypes among
      the cells of a basidiomycete and has interesting implications for the biology of
      A. gallica.

PMID- 10919377
TI  - Classification of sequences expressed during the primordial and basidiome stages
      of the cultivated mushroom Agaricus bisporus.
AB  - Two complementary DNA (cDNA) libraries were constructed from tissues isolated
      from primordia and basidiomes of Agaricus bisporus to characterize genes involved
      in mushroom development. Using single-pass sequencing of 869 cDNA clones, we
      found 477 expressed sequence tags (ESTs), including 466 not previously described
      in the databases for A. bisporus. A BLASTX search revealed that 374 ESTs had
      similarities with protein sequences available from databases; 193 of these ESTs
      were categorized according to their putative function. Most ESTs were assigned to
      one of four roles: metabolism (23%), cell structure (15%), cell growth and
      division (12%), and protein destination and storage (10%). The remaining ESTs
      with putative homologues were classified in 10 additional categories. Many ESTs
      could not be functionally assigned. Based on redundancy levels, at least 4 ESTs
      were preferentially expressed in each tissue type. Sequence analysis also
      suggested the presence of paralog tyrosinase genes in the A. bisporus genome.

PMID- 10919378
TI  - Brefeldin A affects growth, endoplasmic reticulum, Golgi bodies, tubular vacuole
      system, and secretory pathway in Pisolithus tinctorius.
AB  - Brefeldin A (BFA) reduced radial growth in Pisolithus tinctorius at a
      concentration as low as 2 microM. Use of endoplasmic reticulum (ER)-Tracker dye,
      unconjugated BFA, and fluorescent BFA (BODIPY-BFA) allowed comparison of the
      effects of BFA on the endomembrane system of P. tinctorius at the light and
      electron microscope levels. Both ER-Tracker dye and BODIPY-BFA have been shown
      previously to label the ER. Unconjugated BFA and BODIPY-BFA modified the ER
      network and disrupted the tubular vacuole system in the tip region. The
      ultrastructure in freeze-substituted hyphae showed that BFA treatment resulted in
      (i) disruption of the Spitzenkorper, (ii) reduction in number of apical vesicles,
      (iii) redistribution and mild dilation of ER, and (iv) persistence and increased
      size and complexity of Golgi bodies. The effects of BFA on the ER were only
      partially reversible in the time period examined. We conclude that in P.
      tinctorius, BFA as the free metabolite or BODIPY-BFA affects the tubular vacuole
      system as well as anterograde membrane flow between the ER and the Golgi bodies
      and post-Golgi transport.

PMID- 10919379
TI  - Structural requirements for activity of the pheromones of Ustilago hordei.
AB  - Ustilago hordei, the cause of barley-covered smut, initiates mating with
      pheromones. Gene sequence analysis suggested that these pheromones, Uhmfa1 and
      Uhmfa2, would be farnesylated peptides. Although isolation of mating-type
      specific activity was rarely possible, chromatographic separations of culture
      supernatants yielded fractions that stimulated or inhibited mating. Based on
      predicted amino acid sequences and mass spectra of stimulating fractions, a
      series of pheromone analogs were synthesized and their activities were
      determined. Underivatized Uhmfa1 (PGKSGSGLGYSTC) or Uhmfa2 (EGKGEPAPYC) peptides
      were inactive, while peptides that were farnesylated and/or methyl esterified
      specifically induced conjugation tubes by cells of the opposite mating type.
      Uhmfa1 truncated from the amino terminus beyond the lysine lost activity, while
      truncated Uhmfa2 remained partially active. In mating bioassays, a pheromone
      concentration-dependent default mating response was observed. In competition
      studies, shorter Uhmfa1 peptides lacking pheromone activity inhibited activity of
      full-length peptides most effectively when both had the same functional groups.

PMID- 10919380
TI  - A group of expressed cDNA sequences from the wheat fungal leaf blotch pathogen,
      Mycosphaerella graminicola (Septoria tritici).
AB  - A group of expressed sequence tags (ESTs) from the wheat fungal pathogen
      Mycosphaerella graminicola utilizing ammonium as a nitrogen source has been
      analyzed. Single pass sequences of complementary DNAs from 986 clones were
      determined. Contig analysis and sequence comparisons allowed 704 unique ESTs
      (unigenes) to be identified, of which 148 appeared as multiple copies. Searches
      of the nrdb95 protein database at EMBL using the BLAST2x algorithm revealed 407
      (57.8%) sequences that generated high to moderate high scoring pairs with
      proteins of known and unknown function. The rest of the sequences (297) showed
      either weak or no similarities to database entries. Among the unigenes with
      assigned function, 26.7% were involved in primary metabolism and 17.9% were
      associated with protein and RNA metabolism. Fewer clones were ascribed roles in
      signal transduction (4.9%), transport and secretion (6.1%), cell structure
      (3.1%), and cell division (3.6%). Approximately 18.1% of the identities found
      were to hypothetical or unknown proteins mainly from the yeasts Saccharomyces
      cerevisiae and Schizosaccaromyces pombe. Comparison of the 297 sequences with no
      clear function to other fungal ESTs in the public domain revealed 12 sequences
      that had high to moderate similarity to Neurospora crassa, Emericella
      (Aspergillus) nidulans, or Magnaporthe grisea sequences.

PMID- 10919381
TI  - The complete DNA sequence of the nuclear ribosomal RNA gene complex of
      Verticillium dahliae: intraspecific heterogeneity within the intergenic spacer
      region.
AB  - The complete sequence of the nuclear ribosomal DNA gene complex of the
      phytopathogenic fungus Verticillium dahliae has been determined. The tandemly
      repeated unit was 7216 bp long and appears to be the shortest rDNA cluster
      described so far among filamentous fungi. Primer pairs were designed for
      amplification of the region spanning half of the 28S subunit, the intergenic
      spacer (IGS), and the 5' end of 18S subunit of a number of Verticillium strains,
      isolated from various hosts and geographic origins. Great heterogeneity was
      detected in the amplified products of the IGS region resulting in fragments
      varying from 1.6 to 2.0 kb. The majority of Verticillium isolates were classified
      into two groups with 1.6- and 1.7-kb amplified products, respectively. The former
      group included 31 V. dahliae, 7 V. longisporum, and 1 V. albo-atrum isolates,
      whereas the latter included 10 V. dahliae and 1 V. albo-atrum isolates. Sequence
      analysis of representative PCR products of the above groups identified a "hot
      spot" region harboring most of larger insertions, whereas most of the small
      changes were due to transitions and transversions. One V. longisporum isolate
      with a 2.0-kb PCR product contained 13 perfectly conserved tandem repeats of 39
      bp long. The presence of similar incomplete sequences in the corresponding
      regions of V. dahliae, V. longisporum, and V. albo-atrum isolates revealed a
      particular standard motif of insertions in the IGS region of the genus and is
      discussed.

PMID- 10919382
TI  - Alveolar soft part sarcoma: the role of prognostic markers.
AB  - Alveolar soft part sarcoma (ASPS) is a rare malignant neoplasm characterized by
      slow growth and indolent behavior. The role of proliferative markers and tumor
      suppressor genes is unknown in these tumors. To investigate their potential role
      in diagnosis and prognosis, we studied 13 cases of primary ASPS and 14 metastases
      and correlated them with clinicopathologic parameters. Immunohistochemistry was
      performed with anti-p53 and anti-Ki-67 antibodies. Polymerase chain reaction
      after tumor microdissection was performed to search for possible loss of
      heterozygosity in chromosomes 1p, 9p, 17q, 22q, and TP53 to identify possible
      changes that may clarify the histogenesis of these tumors. Four of five (80%)
      primary ASPS cases were positive for Ki-67 and all of them developed later
      metastases. One patient whose tumor did not stain for Ki-67 remained free of
      disease for 9 years. Eleven of 13 (85%) metastases were positive for Ki-67;
      however, there was no correlation with final outcome. All the primary ASPS cases
      analyzed for p53 yielded negative results, but two (15%) of 13 metastases were
      weakly positive. There was no correlation of these markers with prognosis or
      clinicopathologic parameters. No loss of heterozygosity was found except in one
      of nine (11%) informative metastases for D1S165 (at 1p36). Our preliminary data
      suggest that Ki-67-positive immunostaining may be a prognostic indicator for the
      development of metastases in ASPS.

PMID- 10919383
TI  - Mitotic and in situ end-labeling apoptotic indices as prognostic markers in
      malignant mesothelioma.
AB  - The prognostic role of mitotic and apoptotic indices in 60 patients with
      malignant mesothelioma was examined on hematoxylin-eosin-stained sections. The
      findings were compared with apoptotic indices determined by in situ end labeling
      (ISEL) in 35 of the cases. There was a significant survival advantage associated
      with lower mitotic counts and a lower apoptotic index defined by ISEL (P < .05).
      There was no association between the apoptotic index derived from the hematoxylin
      eosin-stained sections and prognosis (P = .90). However, there was a positive
      association between the apoptotic counts calculated from hematoxylin-eosin- and
      ISEL-stained sections (P < .01). The mitotic count and ISEL apoptotic index are
      potentially useful markers of prognosis in malignant mesothelioma.

PMID- 10919384
TI  - Middle ear meningiomas.
AB  - Meningiomas arising in or presenting as middle ear lesions are relatively
      uncommon. This study retrospectively reviews the clinicopathologic features of
      six meningiomas arising in or extending into the middle ear. The patients
      comprise five women and one man ranging in age from 45 to 67 years (median, 55
      years) at the time of surgery. Five tumors arose in the posterior fossa or
      temporal bone region and one tumor arose from the auditory canal itself. Three
      tumors arose on the right side and three on the left. Duration of symptoms before
      surgery involving the middle ear was known in five patients and ranged from 2 to
      13 years (median, 10 years). Symptoms at presentation included gait or balance
      problems (n = 3), chronic otitis media (n = 2), diplopia (n = 2), hearing loss (n
      = 2), pain (n = 1), aural polyp (n = 1), and tinnitus (n = 1). Histologically,
      all six tumors resembled a syncytial (meningotheliomatous) meningioma. Psamomma
      bodies were noted in two tumors and two tumors demonstrated mild nuclear
      pleomorphism. None of the tumors demonstrated histologic features of atypical
      meningioma. Follow-up information was available in five patients. Four patients
      had prior surgery for removal of posterior fossa temporal bone meningiomas and
      developed recurrences involving the auditory canal 60 to 84 months after surgery.
      At the time of most recent follow-up examination, three patients were alive with
      evidence of tumor (65, 112, and 214 months), one patient was alive with no
      evidence of tumor (99 months), one patient died in the postoperative period of
      sepsis and pneumonia following resection of a middle ear recurrence (64 months),
      and one patient was lost to follow-up analysis. Meningiomas arising in or
      extending to the middle ear canal are unusual. They more commonly arise in woman
      and in most cases involve extension of intracranial/cranial tumors into the
      canal.

PMID- 10919385
TI  - Tumor-related thrombotic pulmonary microangiopathy: review of pathologic findings
      and pathophysiologic mechanisms.
AB  - We report a middle-aged woman who died 2 days after presenting with dyspnea and
      severe pulmonary hypertension of unknown etiology. Her symptoms were highly
      suggestive of pulmonary embolism, but clinical evaluations for that disease
      yielded negative results. Autopsy revealed a Krukenberg tumor of the left ovary,
      representing metastatic gastric carcinoma from an occult primary lesion. Although
      the lungs exhibited no gross evidence of pulmonary emboli or neoplasia,
      microscopic examination revealed diffuse microscopic metastases in the pulmonary
      arterial vasculature. The pulmonary arteries exhibited fibrocellular intimal
      proliferation with smooth muscle colonization of the luminal neoplastic lesions
      and associated microthrombi. This disease entity, known as tumor-related
      thrombotic pulmonary microangiopathy, results in generalized microvascular
      obliteration and subsequent pulmonary hypertension. It is a rare condition that
      is distinct from ordinary pulmonary thromboembolism and primary pulmonary
      hypertension. Tumor-related thrombotic pulmonary microangiopathy should be
      considered diagnostically by the autopsy pathologist in cases of rapidly evolving
      pulmonary hypertension in a middle-aged or elderly individual, or respiratory
      failure of unknown cause, especially if there is a history of a visceral
      malignancy.

PMID- 10919386
TI  - Primary anaplastic large cell lymphoma of the adrenal gland.
AB  - Primary adrenal lymphomas are rare. Most reported cases are of B-cell phenotype
      and follow an aggressive clinical course. We report a case of primary anaplastic
      large cell, CD30+ adrenal lymphoma developing in a 62-year-old woman. The patient
      presented with fatigue and vague right upper quadrant pressure. Computed
      tomography revealed bilateral adrenal masses. A right adrenalectomy was
      performed. Histologic evaluation showed islands of large atypical cells
      surrounded by eosinophilic acellular material. The tumor cells stained positive
      for CD45, CD45RO, CD43, and CD30. Epstein-Barr virus genome was identified in
      tumor cells using in situ hybridization. The patient was treated with
      chemotherapy and a 23-month follow-up examination showed no change in the size of
      the opposite adrenal gland and no other evidence of lymphoma.

PMID- 10919388
TI  - Case studies in pathology from the National Museum of Health and Medicine, Armed
      Forces Institute of Pathology.
AB  - The National Museum of Health and Medicine was founded as the Army Medical Museum
      during the American Civil War to document the effects of war wounds and disease
      on the human body. Since then, the Museum has created a collection of documented
      pathologic specimens that can be used to study the gross and microscopic
      appearance of disease conditions. The Museum's collections are a vital link to
      the past and the future of medical research and form a unique national medical
      repository that is used continuously for research, education, and exhibit
      purposes. Today, the Museum in association with its parent institution, the Armed
      Forces Institute of Pathology, provides access to over 130 years of documented
      medical specimens. These specimens allow the unique opportunity to re-examine
      historical classification systems and disease diagnoses. The case of subacute
      chronic osteomyelitis with cortical sequestration of Private J. Potter from the
      Civil War is presented here.

PMID- 10919387
TI  - Collagenous fibroma (desmoplastic fibroblastoma): a unique presentation as a
      goiter in an 88-year-old man.
AB  - Collagenous fibroma (desmoplastic fibroblastoma) is a recently described entity
      in the medical literature. This entity has been reported in various locations,
      including the upper extremities, posterior neck, upper back, lower extremities,
      abdominal wall, and hip. We report an interesting case of an 88-year-old man who
      presented with an apparent goiter involving the right anterolateral neck.
      Histologic studies revealed a well-circumscribed, paucicellular lesion composed
      of stellate and spindle-shaped fibroblasts separated by bundles of collagen. No
      mitotic figures, necrosis, or calcification was observed. The stellate and
      spindle-shaped cells were positive for vimentin and focally positive for desmin,
      indicating myofibroblastic differentiation. Our case exemplifies the diagnostic
      difficulties that these tumors may pose from the clinical and radiologic
      standpoint when they clinically present as a goiter.

PMID- 10919389
TI  - Renal manifestations of plasma cell dyscrasias: an appraisal from the patients'
      bedside to the research laboratory.
AB  - One of the most prominent features of plasma cell dyscrasias is the frequent
      occurrence of renal dysfunction. Renal insufficiency is a common finding with
      elevated serum creatinine in more than 50% of patients with multiple myeloma at
      the time of diagnosis. Renal failure is the second most common cause of death in
      myeloma surpassed only by infections. The reasons for renal failure are
      multifactorial and early accurate diagnosis of the renal alterations may
      significantly impact morbidity and survival. Renal failure may result from
      selective glomerular, tubular interstitial, or vascular pathology or from a
      combination of pathologic events. The disorders associated with plasma cell
      dyscrasias include those characterized by monoclonal light chain deposition,
      encompassing AL-amyloidosis, in addition to the less well-characterized entities,
      such as heavy chain deposition disease and heavy chain amyloidosis. Therefore, it
      is more accurate to refer to them as monoclonal immunoglobulin deposition
      diseases. Staining of renal biopsy specimens for kappa and lambda light chains
      using immunofluorescence techniques and more sophisticated advanced diagnostic
      techniques such as immunoelectron microscopy permit detailed characterization of
      the various renal pathologic manifestations. Renal biopsies can identify
      monoclonal immunoglobulin deposition, and nephrologists have an opportunity to
      detect an underlying plasma cell dyscrasia early in its clinical course before
      overt hematologic alterations become manifest and irreversible renal damage has
      occurred. The overall spectrum of clinical and pathologic manifestations of
      monoclonal immunoglobulin deposition renal diseases has expanded considerably in
      recent years. Recent developments in the research arena promise new therapeutic
      interventions aimed at avoiding or ameliorating renal damage and even promoting
      reversal of some of the pathologic alterations. Currently, the 5-year survival
      rate in myeloma is 29% in white patients and 30% in African-American patients, a
      rather modest improvement from 24% in the 1970s. Bone marrow ablation followed by
      transplantation is available as an alternative mode of therapy that may be
      extraordinarily helpful in a subset of patients with early myeloma.

PMID- 10919390
TI  - Natural variation in susceptibility of Listeria strains to class IIa
      bacteriocins.
AB  - Thirty-one Listeria strains were tested for sensitivity to four class IIa
      bacteriocins, namely, enterocin A, mesentericin Y105, divercin V41, and pediocin
      AcH, and to nisin A. Class IIa bacteriocins displayed surprisingly similar
      antimicrobial patterns ranging from highly susceptible to fully resistant
      strains, whereas nisin A showed a different pattern in which all Listeria strains
      were inhibited. Particularly, it was observed that the strain Listeria
      monocytogenes V7 could not be inhibited by any of the class lIa bacteriocins
      tested. These observations suggest that Listeria strains resistant to the whole
      range of class IIa bacteriocins may occur in natural environments, which could be
      of great concern with regard to the use of these peptides as food preservatives.

PMID- 10919391
TI  - Effect of aluminum on the production of siderophore by Rhizobium sp. (Cicer
      arietinum).
AB  - Rhizobium sp. strain BICC 651 in the presence of 100 microM Al3+ produced a
      threefold higher level of siderophore than in the control culture under iron
      limitation during the stationary phase. Al3+ in increasing concentrations
      resulted in decreased growth, and the effect was alleviated by the addition of
      iron. Siderophore production decreased gradually in Al3+-treated culture as well
      as in the control with the addition of increasing concentrations of Fe3+, and at
      50 microM Fe3+ the level of siderophore was practically undetectable. The
      siderophore binds Fe3+ and also Al3+. The outer membrane protein profiles of the
      bacteria grown in the presence or absence of Al3+ were indistinguishable.

PMID- 10919393
TI  - Methanosarcina mazei strain O1M9704, methanogen with novel tubule isolated from
      estuarine environment.
AB  - A new methanogenic isolate, designated as strain O1M9704 (=OCM 667), was isolated
      from the sediment of the estuarine environment in Eriln Shi, Taiwan. This strain
      grew on trimethylamine and methanol, but it did not catabolize H2-CO2, acetate,
      or formate. Cells grew optimally at 37 degrees C with 0.5% NaCl in neutral pH.
      The cells were stained Gram-negative, nonmotile, irregular coccus 0.3-0.6 microm
      in diameter. A comparison of 16S rDNA sequences phylogenetically related strain
      O1M9704 to Methanosarcina mazei. Gas vacuoles were observed both under phase
      contrast microscope and in thin sections in the electron microscope. Negative
      stain of electron micrographs showed a novel character of strain O1M9704. with
      tubule structure extended out of the cells. The tubule structure and gas vacuoles
      may benefit the adaptation of methanoarchaea in estuarine environment.

PMID- 10919392
TI  - Biodegradation of phenanthrene by a Bacillus species.
AB  - A bacterial strain capable of utilizing phenanthrene as sole source of carbon was
      isolated from soil and identified as a Bacillus sp. The organism also utilized
      naphthalene, biphenyl, anthracene, and other aromatic compounds as growth
      substrates. The organism degraded phenanthrene through the intermediate formation
      of 1-hydroxy-2-naphthoic acid, which was further metabolized via o-phthalate by a
      protocatechuate pathway, as evidenced by oxygen uptake and enzymatic studies.

PMID- 10919394
TI  - Temperature-dependent variation in API 50 CH fermentation profiles of
      Lactobacillus species.
AB  - API 50 CH fermentation profiles of 45 Lactobacillus, one Atopobium, and three
      Weissella strains incubated at 30 degrees C and 37 degrees C were evaluated.
      Atopobium uli and ten species of Lactobacillus showed stable patterns despite the
      change in temperature. The rest of the type strains showed discrepancy between
      the two incubation temperatures: 18 strains lost, 12 additionally fermented
      another sugar, and 7 others fermented a different one in lieu. The variation was
      maximum in L. delbrueckii subsp. delbrueckii. L. malefermentans failed to ferment
      any of the substrates at 37 degrees C. Majority of the food and plant-associated
      strains (mainly heterofermenters) retained distinctive traits at 30 degrees C,
      while most of the animal-associated strains (mostly homofermenters) did so at 37
      degrees C. No general trend was observed; 30 degrees C appeared to promote
      heterofermentation, while 37 degrees C favored homofermenters. Use of API 50 CH
      profiles for taxonomic purpose in most lactobacilli appears reproducible if a
      specific temperature for a species is strictly followed.

PMID- 10919395
TI  - Characterization of the cryptic plasmid pSBO2 isolated from Streptococcus bovis
      JB1 and construction of a new shuttle vector.
AB  - A cryptic plasmid designated pSBO2 (3582 bp) was isolated from Streptococcus
      bovis JB1. The pSBO2 contained putative sites for a double-strand origin (dso), a
      small transcriptional repressor protein (Cop), countertranscribed RNAs (ctRNAs),
      and a replication protein (Rep), which were similar to those from pMV158 and
      pLS1, which were isolated from S. agalactiae, and pWVO1, isolated from
      Lactococcus lactis. The putative single-strand origin (sso) of pSBO2 was similar
      to pER341 and pST1, which were isolated from S. thermophilus. Recombinant plasmid
      designated pSBE2 was constructed to bind pECM184 vector and the DNA fragment
      containing sso, dso, Cop, ctRNAs, and Rep of pSBO2. When pSBE2 was introduced
      into S. bovis 12-U-1 and no8, the plasmids in the transformants had deleted the
      160-bp fragment between sso and dso. This plasmid, designated pSBE2A, was capable
      of transforming Escherichia coli and S. bovis strains 12-U-1 and no8 on high
      frequency; therefore, pSBE2A is an effective shuttle vector.

PMID- 10919396
TI  - Induction of stress shock proteins DnaK and GroEL by phenoxyherbicide 2,4-D in
      Burkholderia sp. YK-2 isolated from rice field.
AB  - The purpose of this work was to investigate the induction of stress shock
      proteins in Burkholderia sp. YK-2 in response to the phenoxyherbicide 2,4
      dichlorophenoxyacetic acid (2,4-D). The stress shock proteins, which contribute
      to the resistance of the cytotoxic effect of 2,4-D, were induced at different 2,4
      D concentrations in exponentially growing cultures of Burkholderia sp. YK-2. This
      response involved the induction of a 43-kDa DnaK and 41-kDa GroEL proteins,
      characterized by SDS-PAGE and Western blot by use of the anti-DnaK and anti-GroEL
      monoclonal antibodies. The total stress shock proteins were analyzed by 2-D PAGE.
      Survival of Burkholderia sp. YK-2 with time in the presence of different
      concentrations of 2,4-D was monitored, and viable counts paralleled the induction
      of the stress shock proteins in this strain.

PMID- 10919397
TI  - Mutations permitting fdhF (formate dehydrogenase H) expression in a selD mutant
      of Salmonella typhimurium.
AB  - Translation of fdhF mRNA, encoding formate dehydrogenase H, requires the context
      specific insertion of selenocysteine at an opal codon. We have cloned the Tn10
      insertion previously shown to block fdhF transcription in Salmonella typhimurium
      and shown that it lies in selD, which encodes phosphoselenate synthetase. A
      spontaneous mutant of the selD::Tn10 strain that expresses anfdhF::lacZ protein
      fusion (where lacZ is fused after the opal codon) was isolated and characterized.
      Suppression showed the same context requirement as previously reported for SelB
      insertion of selenocysteine. The suppressing mutation was mapped by P22 co
      transduction to the 74-75 min of the Salmonella typhimurium genome.

PMID- 10919399
TI  - Genetic fingerprinting of Brevibacterium linens by pulsed-field gel
      electrophoresis and ribotyping.
AB  - Members of Brevibacterium linens display physiological features that are relevant
      for cheese production. The genomes of five B. linens strains deposited on culture
      collections were compared by examining large restriction fragments on pulsed
      field gel electrophoresis and detection of polymorphism at the level of 16S rRNA
      genes. Pulsed-field analysis with the endonucleases DraI and AsnI showed a
      characteristic restriction profile for each strain and allowed the calculation of
      genome sizes ranging between 3.2 and 3.9 Mbp. No linear genomic elements were
      detected. Polymorphisms at the level of 16S rRNA genes were revealed by
      hybridization with an oligonucleotide probe complementary to a universal domain
      of the 16S genes. An EcoRI fragment of 1.4 kb was identified as common to all
      strains under study. According to the number of positive bands detected by the
      probe, at least four rRNA operons must be present on the genome of the B. linens
      strains here studied.

PMID- 10919398
TI  - Phenotypic characterization of polysaccharidases produced by four Prevotella type
      strains.
AB  - Four ruminal Prevotella type strains, P. ruminicola JCM8958T, P. bryantii B 4T,
      P. albensis M384T, and P. brevis ATCC19188T, were characterized for
      polysaccharide-degrading activities with the reducing sugar release assay and
      zymogram analyses. Carboxymethylcellulase, xylanase, and polygalacturonate (PG)
      degrading enzyme activities were determined in cultures grown on oat spelt xylan,
      xylose, arabinose, cellobiose, and glucose as sole growth substrates. P.
      ruminicola and P. albensis showed carboxymethylcellulase induction patterns. When
      xylan was supplied as a sole growth substrate, xylanase activities produced by P.
      bryantii and P. albensis were at least 18- and 11-fold higher, respectively, than
      during growth on other carbohydrates, suggesting that the regulation of the
      xylanases was highly specific to xylan. All strains constitutively produced PG
      degrading enzymes. The corresponding activity of P. bryantii was more than 40
      fold higher than in other strains. Zymogram analyses routinely detected the
      presence of high-molecular-weight (100-170 kDa) polysaccharide-degrading enzymes
      in ruminal Prevotella. Characteristics of the polysaccharide-degrading activities
      showed diversity of ruminal Prevotella species.

PMID- 10919400
TI  - Mutations in the Bacillus subtilis purine repressor that perturb PRPP effector
      function in vitro and in vivo.
AB  - The Bacillus subtilis pur operon repressor (PurR) has a PRPP (5-phosphoribosyl 1
      pyrophosphate) binding motif at residues 199-211. Two PurR PRPP binding region
      mutations (D203A and D204A) were constructed, and the effects on binding of
      repressor to the pur operon control site in vitro and on regulation of pur operon
      expression in vivo were investigated. PRPP significantly inhibited the binding of
      wild-type but not mutant PurR to pur operon control site DNA. In strains with the
      D203A and D204A mutations, pur operon expression in vivo was super-repressed by
      addition of adenine to the growth medium. These results support the role of PRPP
      in modulating the regulatory function of PurR in vivo. YabJ, the product of the
      distal gene in the bicistronic purR operon, is also required for PurR function in
      vivo.

PMID- 10919401
TI  - Effect of insulin on microbial growth.
AB  - The ability of insulin to affect the growth kinetics of Escherichia coli,
      Staphylococcus aureus, Enterococcus faecalis, and Pseudomonas aeruginosa was
      measured. For all organisms, insulin, in the absence of a metabolizable sugar
      source, i.e., glucose or starch in Mueller-Hinton medium, had no effect on
      generation time as compared with a homologous control. Response to insulin, in
      the form of increased or decreased generation times, for both Gram-positive and
      Gram-negative bacteria, was dependent on the concentration of insulin, the
      concentration of glucose present, and the initial concentration of bacteria
      exposed to the glucose and insulin.

PMID- 10919402
TI  - Cloning of a new Bacillus thuringiensis cry1I-type crystal protein gene.
AB  - A new cry1I-type gene, cry1Id1, was cloned from a B. thuringiensis isolate, and
      its nucleotide sequence was determined. The deduced amino acid sequence of
      Cry1Id1 is 89.7%, 87.2%, and 83.4% identical to the Cry1Ia, Cry1Ib, and Cry1Ic
      proteins, respectively. The upstream sequence of the cry1Id1 structural gene was
      not functional as promoter in B. subtilis. The Cry1Id1 protein, purified from
      recombinant E. coli cells, had a toxicity comparable to that of Cry1Ia against
      Plutella xylostella, but it was significantly less active than Cry1Ia against
      Bombyx mori. Cry1Id1 was not active against the coleopteran insect, Agelastica
      coerulea.

PMID- 10919403
TI  - Specificity of a neutral Zn-dependent proteinase from Thermoactinomyces sacchari
      toward the oxidized insulin B chain.
AB  - The proteolytic specificity of the neutral Zn-dependent proteinase from
      Thermoactinomyces sacchari was determined by analysis of the peptides obtained
      after incubation with the oxidized insulin B chain as a substrate. The enzyme is
      an endopeptidase with broad specificity. In total, 12 peptide bonds in the B
      chain of insulin were hydrolyzed. The major requirement is that a hydrophobic
      residue such as Leu, Val, or Phe should participate with the alpha-amino group in
      the bond to be cleaved. However, hydrolysis of bonds at the N-terminal side of
      His, Thr, and Gly was also observed. The peptide bond Leu 15-Tyr 16 in the
      oxidized insulin B chain, which is the major cleavage site for the alkaline
      microbial proteinases, is resistant to the attacks of the enzyme from
      Thermoactinomyces sacchari and other neutral proteinases. The proteolytic
      activity of the Zn-dependent proteinase from T sacchari is different from those
      of other metalloendopeptidases from microorganisms.

PMID- 10919404
TI  - Effect of agglutinins from Rhizobium leguminosarum strain 252 on the activity of
      hydrolytic enzymes.
AB  - Cells of the nitrogen-fixing soil bacterium Rhizobium leguminosarum 252 and its
      hemagglutination-deficient mutant strain 252/7 were found to possess the
      activities of a variety of hydrolytic enzymes. The agglutinin proteins of
      rhizobia diminished beta-glucosidase activity, pectinolytic activity, and acid
      and alkaline phosphatase activities while completely inhibiting proteolytic
      enzyme activity in the bacterial cell. The results here show that rhizobial
      agglutinins are capable of affecting enzyme functioning in Rhizobium.

PMID- 10919405
TI  - Properties of anti-factor VIII inhibitor antibodies in hemophilia A patients.
AB  - Blood coagulation factor VIII functions in the intrinsic pathway of blood
      coagulation as a cofactor by enhancing the assembly of its complex with factors
      IX and X on the surface of activated platelets. This requires factor VIII
      interaction with these two proteins, von Willebrand factor (vWF), and
      phospholipids on the platelet surface. Once factor VIII and factor IX are
      activated by proteolytic cleavage, the complex is able to activate factor X to
      factor Xa by proteolysis. In hemophilia A patients with severe factor VIII
      deficiency, about 30% respond to factor VIII infusion therapy immunologically to
      produce antibodies that inactivate the infused factor VIII and others that are
      noninhibitory. An assay that measures only the inhibitor antibodies demonstrated
      that the factor VIII A2, A3, and C2 domains are the most immunogenic, and domains
      A1 and B are poorly immunogenic or not immunogenic. The specific antibody
      responses to A2, A3, and C2 vary considerably among individuals, and epitopes for
      inhibitor antibodies have been determined for all three. The anti-C2 inhibitors
      prevent factor VIII binding to phospholipids and vWF, and anti-A3 inhibitors
      prevent binding to factor IX (IXa). An inhibitor binding site for factor X has
      been localized to the A1 domain acidic region, leading to inhibition of factor
      VIII/factor X binding by antibodies. This inhibitor mechanism is rare. Because a
      second binding site for factor IX was localized to the factor VIII A2 domain, it
      is likely but not proven that prevention of factor IX binding to factor VIII is
      the inhibitor mechanism for this epitope.

PMID- 10919407
TI  - Factor VIII Inhibitors. Natural autoantibodies and anti-idiotypes.
AB  - Natural antibodies to factor VIII are present in the normal antibody repertoire
      as other self-reactive antibodies to soluble proteins. The question as to whether
      they represent just a chance occurrence linked to the huge diversification of the
      antibody repertoire or whether these antibodies have an actual physiological
      relevance is not entirely settled. Evidence is in favor of a role in the
      maintenance of immune homeostasis, however, namely self-reactive antibodies are
      required to maintain the capacity of the immune system to distinguish self from
      nonself. Anti-factor VIII antibodies pose an interesting case in point because
      they exhibit the capacity to inhibit the function of factor VIII. Such a property
      is neutralized at least in part by the production of corresponding anti-idiotypic
      antibodies. Normal homeostasis can therefore be viewed as a network of
      interacting molecules, idiotypes, and anti-idiotypes; disruption of this
      equilibrium leads to the development of autoimmunity. A question that remains
      open for the time being is whether this network of interactions can be modulated
      in a defined way for the treatment of autoimmune reactions. This would mean
      either passive administration of anti-idiotypic antibodies or active immunization
      with idiotypes. The former has proved to be efficient, and the latter has still
      to be demonstrated. Further, and probably most importantly, is the question of
      the possible application of the idiotypic network concept to the treatment of
      hemophilia patients producing inhibitors. This essentially requires that an
      analysis of the anti-factor VIII immune response be carried out at the clonal
      level. Such work is ongoing in our laboratory.

PMID- 10919406
TI  - Phage display technology: a tool to explore the diversity of inhibitors to blood
      coagulation factor VIII.
AB  - Hemophilia A is a X-linked bleeding disorder that is caused by the functional
      absence of blood coagulation factor VIII. The bleeding tendency in hemophilia A
      patients can be corrected by the administration of plasma-derived or recombinant
      factor VIII concentrates. A serious complication in hemophilia care is the
      development of factor VIII neutralizing antibodies (inhibitors) that arise as a
      consequence of factor VIII replacement therapy. The majority of factor VIII
      inhibitors are directed toward epitopes located within the A2, A3, and C2 domains
      of factor VIII. In this article, we summarize current knowledge on the epitope
      specificity of factor VIII inhibitors. In addition, we will discuss recent
      information on the molecular characteristics of human anti-factor VIII antibodies
      generated by phage display technology.

PMID- 10919408
TI  - Natural antibodies to factor VIII.
AB  - Anti-factor VIII antibodies represent a unique model to study the relationship
      between natural autoreactivity (natural antibodies to factor VIII of healthy
      individuals), disease-associated autoimmunity ("spontaneous" factor VIII
      inhibitors of patients with anti-factor VIII autoimmune disease) and antigen
      driven immune responses (immune inhibitors in multitransfused patients with
      hemophilia A) to a single human protein antigen. Although natural and disease
      associated anti-factor VIII antibodies are not readily distinguished based on the
      comparison of their isotypic distribution and epitope mapping, available studies
      of cross-reacting idiotypes suggest that factor VIII inhibitors in patient's
      plasma encompass two populations of anti-factor VIII antibodies. Some antibodies
      result from the clonal expansion of B lymphocytes that exist before treatment
      with factor VIII and secrete anti-factor VIII antibodies with properties similar
      to those of natural anti-factor VIII antibodies present in healthy individuals;
      other inhibitors are produced by B cell clones that have undergone affinity
      maturation and hypermutation of the V regions of the antibodies they produce. The
      implications for the treatment of patients with anti-factor VIII inhibitors are
      discussed.

PMID- 10919409
TI  - Correlation between factor VIII genotype and inhibitor development in hemophilia
      A.
AB  - The development of neutralizing antibodies, or inhibitors, against infused factor
      VIII represents a significant complication of treatment for hemophilia A.
      Although it is likely that both genetic and environmental factors influence
      whether patients form inhibitors, correlations between types of factor VIII
      mutations and inhibitor development are becoming apparent. Approximately 20% of
      all patients with severe hemophilia A generate inhibitors. Of these inhibitor
      patients, 90% have inversions, large deletions or nonsense mutations of the
      factor VIII gene that would be predicted to eliminate production of factor VIII
      antigen. In contrast to patients with severe disease, inhibitor formation in
      patients with mild/moderate hemophilia A is rare. Inhibitor patients with
      mild/moderate disease typically have missense mutations that may cause local
      conformational changes within immunogenic domains of factor VIII and lead to
      production of dysfunctional antigen. Taken together, hemophilia A patients are
      predisposed to inhibitor development with mutations causing infused factor VIII
      to be perceived as either 1) a completely novel antigen or 2) an immunologically
      altered antigen.

PMID- 10919410
TI  - Factor VIII inhibitors. Potential for prevention of inhibitor formation by immune
      tolerance.
AB  - Factor VIII inhibitory antibodies occur following treatment in more than 30% of
      subjects with severe factor VIII deficiency. Almost all inhibitor formation
      occurs in subjects with little if any circulating factor VIII. In the absence of
      in utero exposure to endogenous or maternal factor VIII, these subjects probably
      recognize factor VIII as a non-self antigen; in other words, their immune systems
      fail to become tolerant to factor VIII. This opens up the possibility of
      preventing inhibitor formation by neonatal induction of tolerance to factor VIII.
      The various possible approaches include prenatal or neonatal tolerance by the
      parenteral or oral administration of purified factor VIII protein or factor VIII
      encoding DNA. The results of preliminary experiments in mice indicate that
      feeding newborns a series of low doses of factor VIII does not suppress induction
      of anti-factor VIII antibody. Whether tolerance can be achieved by feeding mice
      high doses of factor VIII or by intrauterine or neonatal administration of factor
      protein or DNA remains to be determined.

PMID- 10919411
TI  - Inhibitor antibodies to factor VIII and factor IX: management.
AB  - Inhibitor antibodies directed against factor VIII or factor IX present challenges
      to the clinician. Fortunately, several management options are available, although
      each has disadvantages as well as advantages. Alloantibodies against factor VIII
      (which develop in 25 to 50% of children with severe hemophilia A, as well as in a
      small percentage of children with mild or moderate hemophilia A) may be low titer
      and transient or may be high titer. Most patients with high-titer problematic
      inhibitors now try to eliminate the inhibitor by using one of several immune
      tolerance induction (ITI) regimens. For treatment of bleeding episodes in
      patients who have high-titer (> or = 5 Bethesda units) inhibitors, one can use a
      prothrombin complex concentrate (PCC) (preferably an activated PCC [APCC]),
      recombinant (r) factor VIIa, or porcine factor VIII. The choice of product is
      generally dependent on the type and severity of the patient's bleeding, degree of
      cross-reactivity of the patient's inhibitor with porcine factor VIII, physician
      familiarity with the product, product availability, and cost. In persons with
      hemophilia B, alloantibodies occur in only 1 to 3% of severely affected
      individuals. However, in roughly half of those who develop inhibitors,
      anaphylaxis or severe allergic reactions occur on infusion of any type of factor
      IX-containing product. This phenomenon usually develops after relatively few
      exposures to factor IX; thus it is recommended that the first 10 to 20 infusions
      of factor IX given to children with severe hemophilia B be given in a setting
      equipped for treatment of shock. For treatment of bleeding episodes in patients
      with severe allergic reactions, rF VIIa is the treatment of choice. ITI has been
      less successful in hemophilia B patients with inhibitors than in those with
      hemophilia A, and in a subgroup of patients with severe allergic reactions who
      were desensitized to factor IX and then tried on ITI, results were even poorer.
      Additionally, several developed nephrotic syndrome while on ITI. For hemophilia B
      patients with inhibitors who do not have allergic reactions to factor IX,
      bleeding episodes can be treated with PCC or APCC or with rF VIIa. Autoantibodies
      directed against factor VIII are rare but can occur in a variety of settings.
      They occur mainly in adults, and bleeding is often severe and life threatening.
      Although some factor VIII autoantibodies disappear spontaneously, most require
      immunosuppression. Corticosteroids and cyclophosphamide are generally
      recommended. For treatment of bleeding, therapeutic options include (human)
      factor VIII concentrates, porcine factor VIII, APCC, and rFVIIa. The choice of
      product is generally determined by the consulting hematologist's familiarity with
      the product, product availability and cost, as well as response to treatment.

PMID- 10919412
TI  - Factor VIII inhibitors. Immune tolerance induction: is it cost effective? We know
      too little.
AB  - The development of an inhibitor in a hemophiliac is a serious clinical problem.
      Many inhibitors have high titers, and thus one cannot guarantee hemostasis. The
      prevalence of this transfusion-transmitted disease reaches as high as 35%, even
      with newer products. The costs of product use for inhibitor patients are
      significantly higher than for those without an inhibitor. For more than 20 years,
      using the concept of antigen overload, several regimens have existed for the
      induction of immune tolerance to eradicate these inhibitors. Registries exist
      reviewing the results of these regimens in the United States and internationally.
      Although much has been garnered about predictors of outcomes, we have much to
      learn about who the ideal candidates are, what optimal regimens are, and when to
      stop, as well as how to maintain a success. The costs of managing an inhibitor
      patient with and without human immunodeficiency virus (HIV) have caused managed
      care programs to seriously challenge the use of these regimens. Data are needed
      to provide the cost benefit of immune tolerance.

PMID- 10919413
TI  - Factor VIII inhibitors. Laboratory diagnosis of inhibitors.
AB  - The diagnosis of inhibitors of blood coagulation is often the most challenging
      problem in the clinical laboratory. Immediate attention must be given to the
      following patient groups whose principal laboratory abnormality is the prolonged
      activated partial thromboplastin time (aPTT): the patient with (1) hemophilia who
      previously responded to an adequate dose of clotting factor product and now fails
      to show effective clinical response to the same replacement concentrate; (2)
      previously benign clinical history who now presents with soft tissue bleeding or
      emergent internal hemorrhaging; (3) sudden onset of generalized ecchymoses who
      was previously well; (4) postpartum state; (5) malignancy, lymphoma, rheumatoid
      arthritis, or other autoimmune disorders; and (6) drug reactions. Immediate
      attention must be given to the prolonged prothrombin time (PT), aPTT, and
      thrombin time (TT) in order to respond to urgent queries from a perplexed
      internist, hematologist, intensivist, or surgeon caring for a patient with
      unexpected bleeding. Sometimes the problem of a prolonged "clotting time" arises
      preoperatively, causing unanticipated delay in operative procedures. For this
      reason, the laboratory support, usually in the coagulation section of a clinical
      laboratory or reference laboratory, must be quick, unequivocal and precise. The
      most common finding is an isolated mild, moderate, or severe prolongation of the
      aPTT with a normal PT, TT, and platelet count. The aPTT mixing study (The Mix),
      usually modified for time and temperature, along with appropriate controls, is
      the seminal test. This is the basis for all further testing. It may be supported
      by direct factor assays, and, therefore, the laboratory must know the reagent
      responsiveness and sensitivity for each clotting factor. By definition, complete
      correction of the aPTT in a 1:1 mix of patient and reference plasma is a factor
      deficiency. In this article, incomplete or minimal correction of The Mix will be
      characterized with particular attention to the various inhibitor assays, in other
      words, Oxford, Bethesda, and Nijmegen assays and the enzyme-linked immunosorbent
      assay (ELISA). An investigative approach to final characterization of the
      intensity (quantification) of the inhibitor and the exclusion of a lupus
      anticoagulant (LA) will be discussed.

PMID- 10919414
TI  - Anaphylaxis in patients with hemophilia.
AB  - Anaphylactic reactions are rare emergencies observed in hemophilia patients. In
      hemophilia (B) (HB) patients they typically occur coincident with the development
      of an inhibitor. It is important to be aware of the possibility of such
      reactions, and the patient's family should be educated at the time of initial
      diagnosis and discussion. Because these reactions typically occur within the
      first 10 to 20 treatment courses, the first few infusions should be given in a
      hospital/clinic setting equipped to manage such emergencies. Obtaining the exact
      genotype may identify the HB patients at risk for this complication. When immune
      tolerance induction (ITI) is attempted in patients with HB inhibitors and
      anaphylaxis, the physician should be vigilant in detecting proteinuria.

PMID- 10919415
TI  - Tunnelling epidural catheters: a worthwhile exercise?

PMID- 10919416
TI  - Prophylactic amrinone for weaning from cardiopulmonary bypass.
AB  - This prospective, randomised, double-blind, controlled clinical study was
      performed at a single tertiary referral centre to test the hypothesis that the
      prophylactic administration of amrinone before separation of a patient from
      cardiopulmonary bypass decreases the incidence of failure to wean, and to
      identify those patients who could be predicted to benefit from such pre-emptive
      management. Two hundred and thirty-four patients, scheduled to undergo elective
      cardiac surgery, were randomly allocated to receive either a bolus dose of 1.5 mg
      x kg(-1) amrinone over 15 min, followed by an infusion of 10 microg x kg(-1) x
      min(-1), or a bolus of placebo of equal volume followed by an infusion of
      placebo. Treatment with amrinone or placebo was initiated upon release of the
      aortic cross-clamp, before weaning from cardiopulmonary bypass. Anaesthetic
      technique, monitoring and myocardial preservation methods were standardised for
      both groups. Significantly fewer patients failed to wean in the group that
      received prophylactic amrinone than in the control group (7 vs. 21%, p = 0.002).
      Amrinone improved weaning success regardless of left ventricular ejection
      fraction, although this benefit was statistically significant only in the group
      with left ventricular ejection fractions > 55%. Of the 32 patients who failed to
      wean from cardiopulmonary bypass, 14 had normal pre-operative left ventricular
      ejection fractions.

PMID- 10919417
TI  - The effect of sevoflurane on implicit memory: a double-blind, randomised study.
AB  - Forty-eight gynaecological patients were randomly allocated to three groups
      (target end-tidal sevoflurane concentration 1.2, 1.5 or 2%), and into subgroups
      for positive or neutral suggestion. Anaesthesia was induced by inhalation of
      sevoflurane in oxygen. When the target concentration was achieved, the bispectral
      index, computed from a bi-frontal electroencephalogram, was noted. One of two
      eight-word lists was then played to prime implicit memory, followed by a positive
      or neutral suggestion. After surgery, each patient tried to identify 24 words
      obscured by background noise. Priming increased the likelihood of identifying
      words in the 1.2% group only, i.e. there was evidence of implicit memory in this
      group. There was no evidence of a therapeutic effect of positive suggestion (p =
      0.3), but the power of this part of the study was low. The bispectral index did
      not achieve statistical significance as an indicator of susceptibility to
      priming.

PMID- 10919418
TI  - Increases in serum concentrations of cardiac proteins and the prediction of early
      postoperative cardiovascular complications in noncardiac surgery patients.
AB  - We investigated the use of measurements of serum concentrations of the cardiac
      proteins troponins I and T as biochemical markers of myocardial cell damage in 80
      patients undergoing vascular or major orthopaedic surgery. Holter
      electrocardiographic monitoring was carried out before surgery and for 3 days
      after surgery. Blood samples for troponins I and T and creatine kinase-MB
      isoenzyme were taken on each of these 4 days. Outcome was assessed at 3 months
      using a patient questionnaire, general practitioner follow-up and case notes
      review. Silent postoperative myocardial ischaemia was detected in 21 patients;
      increases in troponins I and T and creatine kinase-MB occurred in four, six and
      17 of these patients, respectively. Eight patients suffered major postoperative
      complications (cardiac death, myocardial ischaemia, congestive cardiac failure,
      unstable angina and cerebrovascular accident) and 21 minor complications (poorly
      controlled hypertension needing increased or new additional treatment,
      palpitations, increased tiredness or shortness of breath in the absence of known
      respiratory disease). There were no associations between postoperative ischaemia
      and cardiac protein concentrations. The relative odds for the associations of
      major adverse outcome at 3 months after surgery and postoperative ischaemia or
      increased serum concentrations of the three proteins were 5.39 [95% confidence
      intervals 1.16-27.67] for postoperative ischaemia; 5.64 [1.07-31.00] for creatine
      kinase-MB isoenzyme; 17.00 [2.20-116.54] for troponin T and 13.20 [1.12-135.00]
      for troponin I. We found troponin T to be the only prospective marker for both
      major and minor cardiovascular complications (relative odds 10.65 [1.26-252.88]).

PMID- 10919419
TI  - Cricoid pressure: which hand?
AB  - We studied 20 anaesthetic assistants applying simulated cricoid pressure with the
      left or right hand in random order. Simulated cricoid pressure was continued for
      up to 5 min with one hand and then, after resting, with the other hand. Applied
      pressure was measured at intervals and the subjects were blind to the results.
      Nineteen assistants were right-handed and all routinely applied cricoid pressure
      with their right hand. Mean (SD) force applied during simulated 'awake' cricoid
      pressure was 13.8 (5.7) N with either left or right hand, and during
      'anaesthetised' cricoid pressure it was initially 25.1 (8.2) N and 24.7 (8.8) N
      with left or right hand, respectively. Mean force was maintained above 20 N and
      below 30 N throughout the study period with either hand. Force applied with the
      left hand was significantly lower than with the right hand but the difference was
      clinically insignificant (0.4 N). Inadequate or excessive force was more
      frequently associated with use of the left hand (p < 0.0001). Cricoid pressure
      was released before 5 min in three cases, two left-handed and one right-handed.
      Our results demonstrate that anaesthetic assistants apply a lower force than is
      classically taught and are able to maintain the force with either hand for a
      sustained period. Application with the left hand is justified where clinically
      indicated but may have a lower margin for error than when applied with the right
      hand.

PMID- 10919420
TI  - Hypoxia during upper gastrointestinal endoscopy with and without sedation and the
      effect of pre-oxygenation on oxygen saturation.
AB  - In Study A, the incidence of arterial oxygen desaturation was studied using pulse
      oximetry (SaO2) in 100 sedated and 100 nonsedated patients breathing room air who
      underwent diagnostic upper gastrointestinal endoscopy. Hypoxia (SaO2 92% or less
      of at least 15 s duration) occurred in 17% and 6% of sedated patients and
      nonsedated patients, respectively (p < 0.03). Mild desaturation (SaO2 94% or less
      and less than 15 s duration) occurred in 47% of sedated patients compared with
      12% of nonsedated patients (p < 0.001). In Study B, the effects of supplementary
      oxygen therapy and the effects of different pre-oxygenation times on arterial
      oxygen saturation (SaO2) in sedated patients were studied using pulse oximetry.
      One hundred and twenty patients who underwent diagnostic upper gastrointestinal
      endoscopy with intravenous sedation were studied. Patients were randomly
      allocated to one of four groups: Group A (n = 30) received no supplementary
      oxygen while Groups B-D received supplementary oxygen at 4 1 x min(-1) via nasal
      cannulae. The pre-oxygenation time in Group B (n = 30) was zero minutes, Group C
      (n = 30) was 2 min and Group D (n = 30) was 5 min before sedation and
      introduction of the endoscope. Hypoxia occurred in seven of the 30 patients in
      Group A and none in groups B, C and D (p < 0.001). We conclude that desaturation
      and hypoxia is common in patients undergoing upper gastrointestinal endoscopy
      with and without sedation. Sedation significantly increases the incidence of
      desaturation and hypoxia. Supplementary nasal oxygen at 4 1 x min(-1) in sedated
      patients abolishes desaturation and hypoxia. Pre-oxygenation confers no
      additional benefit.

PMID- 10919421
TI  - A comparison of opiate- and epidural-induced alterations in splanchnic blood flow
      using intra-operative gastric tonometry.
AB  - Several methods are available to measure splanchnic blood flow and gut ischaemia.
      Tonometry is most practical for peri-operative use. Epidural blockade from T5 to
      T11 causes mesenteric arteriovenous vasodilation and may increase splanchnic
      blood flow. This study assesses the ability of tonometry to measure differential
      effects of opiate and epidural analgesia on splanchnic blood flow. Forty patients
      for elective colorectal surgery were randomly allocated to receive epidural
      infusion or intravenous morphine. Gastric mucosal PCO2, pHi, standard pHi, PCO2
      gap and pH gap were measured after induction and on termination of surgery. These
      parameters were within normal limits at the end in most cases and there was no
      significant difference between the groups. The complication rate was similar in
      both groups and was not correlated with low pHi, but was correlated with blood
      loss. We were unable to demonstrate a difference in splanchnic perfusion, as
      assessed by gastric tonometry, between the two groups.

PMID- 10919422
TI  - Setting targets for sedation with a target-controlled propofol infusion.
AB  - We studied 30 unpremedicated patients undergoing muscle biopsy under femoral
      nerve block to determine sedation levels reached with a Diprifusor target
      controlled propofol infusion, in order to establish the equivalent of the ED50
      for different levels of depth of sedation. Infusion was started at 0.8 microg x
      ml(-1) and altered by increments of 0.1 microg x ml(-1) after equilibrium between
      target and calculated concentrations, until the desired level of sedation was
      reached. The ED50 target propofol concentrations for sedation at sedation levels
      2 (drowsy), 3 (drowsy, responds to verbal stimulation) and 4 (responsive to
      physical stimulation only) were 1.0 microg x ml(-1), 1.6 microg x ml(-1) and 2.1
      microg x ml(-1), respectively. At sedation level 3, several patients exhibited
      spontaneous movement, hindering surgery. Oxygen supplementation is recommended
      for sedation at level 4.

PMID- 10919424
TI  - Brainstem death and ventilator trigger settings.
AB  - A patient with cerebral infarction was certified clinically brainstem dead.
      However, 4 h after the diagnosis of death, while the patient was being ventilated
      using the biphasic positive airway pressure mode, the 'assist' indicator light on
      the Drager Evita 2 ventilator illuminated intermittently. There was no evidence
      of spontaneous breathing. 'Triggering' was probably caused by a decrease in
      airway pressure in time with cardiac contraction. The trigger flow rate is
      crucial as factors other than the patient's inspiratory effort can initiate flow
      from the ventilator with very sensitive settings.

PMID- 10919423
TI  - The oesophageal-tracheal Combitube Small Adult.
AB  - Airway management during gynaecological laparoscopy is complicated by
      intraperitoneal carbon dioxide inflation, Trendelenburg tilt, increasing airway
      pressures and pulmonary aspiration risk. We investigated whether the oesophageal
      tracheal Combitube 37 Fr SA is a suitable airway during laparoscopy. One hundred
      patients were randomly allocated to receive either the Combitube SA (n = 49) or
      tracheal intubation (n = 51). Oesophageal placement of the Combitube was
      successful at the first attempt [16 (3) s]. Peak airway pressures were 25 (5)
      cmH2O. An airtight seal was obtained using air volumes of 55 (13) ml
      (oropharyngeal balloon) and 10 (1) ml (oesophageal cuff). Significant
      correlations were observed between patient's height and weight and the balloon
      volumes necessary to produce a seal. Similar findings were recorded for the
      control group, with tracheal intubation being difficult in three patients. The
      Combitube SA provided a patent airway during laparoscopy. Non-traumatic insertion
      was possible and an airtight seal was provided at airway pressures of up to 30
      cmH2O.

PMID- 10919425
TI  - Translaryngeal tracheostomy in highly unstable patients.
AB  - Percutaneous tracheostomy is a widely accepted and commonly performed technique
      for attaining long-term airway access in critically ill patients. However, severe
      respiratory failure and coagulopathy are relative contraindications for these
      procedures. We describe two patients with severe respiratory failure and
      inhibitor-complicated haemophilia A who underwent elective percutaneous
      tracheostomy performed translaryngeally, using the new Fantoni technique. Apart
      from two minor bleeding episodes in the haemophilic patient which were controlled
      promptly, no other complications occurred. If certain precautions are observed
      carefully, we believe that translaryngeal tracheostomy is a procedure which is
      superior to other percutaneous techniques and safe even in patients with severe
      respiratory failure and coagulopathy.

PMID- 10919426
TI  - Wegener's granulomatosis: an unusual cause of upper airway obstruction.
AB  - A 10-year-old child with a 2-month history of tracheitis presented with acute
      stridor, for which he required tracheostomy. Granulation tissue was found in the
      subglottic region and he was treated with antibiotics and corticosteroids. A week
      after successful decannulation of his tracheostomy, his stridor recurred and, on
      endoscopy under general anaesthesia, circumferential granulomas extending into
      both main bronchi were found. A diagnosis of Wegener's granulomatosis was made
      and confirmed on histology.

PMID- 10919427
TI  - The effect of humidification and smoking habit on the incidence of adverse airway
      events during deepening of anaesthesia with desflurane.
AB  - The effect of two levels of humidification on the incidence of adverse airway
      events was studied in 58 adult female patients during deepening of anaesthesia
      using up to 12% desflurane. Humidification was provided by a breathing system
      filter with either low moisture-conserving performance (17.2 mg x l(-1) at 0.5 1
      tidal volume, Group L) or high moisture-conserving performance (33.5 mg x l(-1)
      at 0.5 1 tidal volume, Group H). Forty-eight per cent of patients smoked and
      there were more smokers in Group L than in Group H. Adverse airway events
      consisted of coughing and laryngospasm. For coughing, the dominant explanator was
      smoking. When both humidity and age were included in the analysis, there was a
      significant smoking-humidity interaction (p < 0.05), such that high humidity
      decreased the incidence of coughing in nonsmokers but not in smokers. The
      incidence of laryngospasm was significantly lower in Group H than in Group L (p <
      0.05). We conclude that when patients inspire high concentrations of desflurane
      during induction of anaesthesia, increasing humidification to the levels achieved
      in this study decreases the incidence of coughing among nonsmokers and of
      laryngospasm in both smokers and nonsmokers.

PMID- 10919429
TI  - The implications of anaesthetising the brainstem dead.

PMID- 10919428
TI  - Failed tracheal intubation in obstetrics: a 6-year review in a UK region.
AB  - In the South Thames (West) region of the United Kingdom, during a 6-year period
      from 1993 to 1998, there was a significant increase in the Caesarean section rate
      accompanied by a significant decrease in the use of general anaesthesia for
      operative delivery. During this time, there were 36 failed tracheal intubations
      occurring in 8970 obstetric general anaesthetics (incidence 1/249). There was no
      significant difference in the incidence of failed tracheal intubation in each of
      the six years. In 24 of the 26 cases for which the patients' notes could be
      examined, there was either no recording of preoperative assessment, a failure to
      follow an accepted protocol for failed tracheal intubation, or no follow-up.

PMID- 10919430
TI  - The implications of anaesthetising the brainstem dead.

PMID- 10919431
TI  - Interpreting the base deficit.

PMID- 10919432
TI  - Anaesthetic implications of endovascular repair of aortocaval fistula.

PMID- 10919434
TI  - Spinal anaesthesia in Paget's disease of bone.

PMID- 10919433
TI  - Adult spina bifida.

PMID- 10919435
TI  - Not another scoring system.

PMID- 10919436
TI  - Percutaneous tracheostomy--an improvement in safety.

PMID- 10919437
TI  - A modification of the percutaneous tracheostomy technique.

PMID- 10919438
TI  - Sterilisation of laryngoscopes.

PMID- 10919439
TI  - A survey into the number of times laryngeal masks are used.

PMID- 10919440
TI  - Preformed laryngeal masks.

PMID- 10919441
TI  - Stylet hazard.

PMID- 10919442
TI  - A device for cricothyrotomy and retrograde intubation.

PMID- 10919443
TI  - Bronchoscopy during percutaneous tracheostomy.

PMID- 10919444
TI  - Unusual airway obstruction leading to contralateral pneumothorax following
      pneumonectomy.

PMID- 10919446
TI  - Glycinothorax revisited.

PMID- 10919445
TI  - Mediastinal tamponade.

PMID- 10919447
TI  - Magnetic resonance imaging and target-controlled infusions with propofol.

PMID- 10919448
TI  - Propofol-induced violent coughing.

PMID- 10919449
TI  - Pyrexial patients are not always ill.

PMID- 10919450
TI  - Temperature monitoring in paediatric practice.

PMID- 10919451
TI  - Pressure sore following low-dose epidural infusion.

PMID- 10919452
TI  - Performing epidural insertion under general anaesthesia.

PMID- 10919453
TI  - Isoflurane entonox mixtures for pain relief during labour.

PMID- 10919454
TI  - Training in obstetric general anaesthesia: a vanishing art?

PMID- 10919455
TI  - Ambulatory labour analgesia.

PMID- 10919456
TI  - Speed of onset of regional analgesia in labour.

PMID- 10919457
TI  - Speed of onset of regional analgesia in labour.

PMID- 10919458
TI  - Speed of onset of analgesia in labour and maternal satisfaction: comparison of
      epidural and combined spinal-epidural.

PMID- 10919459
TI  - Anaesthesia for the elderly parturient.

PMID- 10919460
TI  - Transcutaneous electrical nerve stimulation (TENS): an unusual source of
      electrocardiogram artefact.

PMID- 10919461
TI  - Management of a septic patient with postdural puncture headache.

PMID- 10919462
TI  - Preparation of anaesthetic drugs in obstetric theatre.

PMID- 10919463
TI  - The role of lateral table tilt in obstetric anaesthesia.

PMID- 10919464
TI  - Hospital-acquired infections.

PMID- 10919465
TI  - Combined spinal-epidural technique for diagnostic lumbar puncture in the
      intensive care unit.

PMID- 10919466
TI  - Latex-free central venous lines.

PMID- 10919467
TI  - Latex allergy--potentially a painful postoperative problem.

PMID- 10919468
TI  - Accidental intra-arterial injection via the venous limb of a dual pressure
      transducer system.

PMID- 10919469
TI  - Blocked oxygen tubing.

PMID- 10919470
TI  - Evaluation of a needle-free injection system for local anaesthesia prior to
      venous cannulation.

PMID- 10919471
TI  - Anaesthetic room pollution: the dangers of prevention.

PMID- 10919472
TI  - Are you being framed?

PMID- 10919473
TI  - Mobile communications in hospitals.

PMID- 10919474
TI  - Training for critical incidents.

PMID- 10919475
TI  - A call for unity.

PMID- 10919476
TI  - 'Speaking in tongues'. Fixation on a non-native language at induction of
      anaesthesia.

PMID- 10919477
TI  - Anaesthesia on the World Wide Web: is reliable patient information available on
      the Internet?

PMID- 10919478
TI  - Who wants to be a millionaire?

PMID- 10919479
TI  - Tongue piercing.

PMID- 10919480
TI  - Safety notice MDA SN2000(07). Medical gas cylinders: risk of fire.

PMID- 10919481
TI  - Peripheral neuropathy: zalcitabine reassessed.
AB  - Given that the long-term medical management of HIV infection necessitates making
      best use of all available antiretrovirals, it is somewhat surprising that the
      nucleoside analogue reverse transcriptase inhibitor (NRTI) zalcitabine is less
      commonly used. This may be due to the potential for peripheral neuropathy (PN)
      which has been associated with the use of this drug. The perception that
      zalcitabine is poorly tolerated appears to have arisen largely from the results
      of early monotherapy trials in patients with AIDS and low CD4 cell counts. In
      contrast, results of more recent studies show that PN is relatively infrequent
      when zalcitabine is used in combination with other antiretrovirals in current
      treatment settings.

PMID- 10919482
TI  - Post-exposure prophylaxis following non-occupational exposure to HIV: risks,
      uncertainties, and ethics.
AB  - Post-exposure prophylaxis (PEP) is the standard of care for occupational exposure
      to HIV infection although it has not been evaluated following non-occupational
      exposure. Although the most effective methods for preventing HIV infection remain
      those that prevent exposure to HIV in the first place, this article discusses the
      dilemmas surrounding post-exposure therapy following non-occupational exposure.

PMID- 10919483
TI  - Integrated sexual healthcare: the development and review of one model of service
      delivery.
AB  - Sexual health is topical with many factors impacting upon its concept and hence
      provision. In 1995 the Sexual Health Service in East Berkshire was formed by the
      integration of the clinical services of Family Planning, Genitourinary and HIV
      Medicine with Sexual Health Promotion. The philosophy of the service is to
      provide holistic sexual healthcare in one visit, on one site by one clinical
      team. This article outlines the practical developments and the strengths and
      weaknesses of this model of service.

PMID- 10919484
TI  - The association of Chlamydia trachomatis and Mycoplasma genitalium with non
      gonococcal urethritis: observations on heterosexual men and their female
      partners.
AB  - Our objectives were to study the distribution of Chlamydia trachomatis and
      Mycoplasma genitalium in men with or without non-gonococcal urethritis (NGU) and
      their respective female partners. A case-control study was carried out to which
      men with or without NGU and their female partners were recruited. All study
      participants were tested for the presence of C. trachomatis and M. genitalium. An
      analysis firstly of the distribution of each of these microorganisms among men
      with or without urethritis and their respective female partners was carried out.
      Furthermore, we examined the association of each of these microorganisms and NGU
      when the other had been excluded. Chlamydia trachomatis was present in 14 (36%)
      of 39 men with NGU compared to none of 12 men without NGU (P=0.022). The
      prevalence rates for female partners of men with NGU were 10 (26%) of 39 compared
      to none of 12 partners of men without NGU (P=0.092). M. genitalium was detected
      in 12 (33%) of 36 men with NGU compared to 1 (9%) of men without NGU (not
      significant; P=0.147). The prevalence rates for female partners of men with NGU
      were 10 (32%) of 31 women compared to none of 7 partners of men without NGU (not
      significant; P=0.156). There was a greater concordance than discordance of
      carriage of each of the 2 microorganisms among the study couples and each tended
      to be carried independently of the other by men. Analysis of the association
      between the presence of C. trachomatis in men and NGU was significantly improved
      by the exclusion of men with M. genitalium (P=0.0058). Likewise, the association
      between the presence of M. genitalium in men and NGU was significantly improved
      by the exclusion of couples in whom either the man or woman was C. trachomatis
      positive (P=0.049). The independent carriage of C. trachomatis and M. genitalium
      by men with NGU, coupled with the improved association between each pathogen and
      NGU by exclusion of the other provides support for the separate role of each in
      the aetiology of NGU.

PMID- 10919485
TI  - National assessment of PID diagnosis, treatment and management in general
      practice: England and Wales.
AB  - A questionnaire based audit was used to evaluate the diagnosis and management of
      suspected pelvic inflammatory disease (PID) cases by general practitioners (GPs)
      in England and Wales. Responses were compared against a clinical management 'gold
      standard' devised by an independent group of GPs and specialists. Two hundred and
      ninety-seven (38%) of the 781 questionnaires were returned. Only 21 (7%) had all
      'gold standard' sections correct. Diagnostic quality was significantly higher
      when the clinician was female compared with male (odds ratio [OR]=2.34; 95%
      confidence limits [CL]=1.19-4.63) and diagnostic quality increased with
      increasing socioeconomic deprivation. This is the first evaluation of the
      diagnosis and management of PID by GPs in England and Wales. The unusually poor
      response rate to a Medical Research Council General Practice Research Framework
      (MRC GPRF) study may reflect low disease awareness and sub-optimal management.
      This represents a fundamental obstacle to effective intervention and
      surveillance. Effective intervention will only be possible if diagnostic practice
      and management are improved substantially.

PMID- 10919486
TI  - Undergraduates' perception of HIV immunization: attitudes and behaviours as
      determining factors.
AB  - The development of a vaccine to prevent human immunodeficiency virus (HIV)
      infection is a highly desirable goal. However, there may be a number of
      psychosocial barriers to HIV vaccine acceptance. The purpose of this study was to
      evaluate the relationship of health beliefs and health lifestyles to
      acceptability of hypothetical HIV immunization. The subjects were 549 college
      students who completed self-administered questionnaires that addressed health
      beliefs, health behaviours, and acceptability of hypothetical HIV vaccines.
      Results showed that all 6 variables of health beliefs, based in part on the
      Health Belief Model, independently predicted HIV vaccine acceptability. For the
      overall sample, 5 health behaviours were significantly correlated with HIV
      vaccination: diet, smoking, drug use, alcohol use, and prior sexual experience.
      The results suggest that universal HIV acceptance cannot be assumed, and that
      certain health beliefs and behaviours are likely to influence decisions regarding
      HIV immunization.

PMID- 10919487
TI  - Serum lipid levels associated with increased risk for cardiovascular disease is
      associated with highly active antiretroviral therapy (HAART) in HIV-1 infection.
AB  - The long-term effects of fat metabolism, storage and utilization in HIV-1
      infected patients on highly active antiretroviral therapy (HAART) including a
      protease inhibitor are profound and cause increasing concern. The main importance
      of these lipid/metabolic disorders lies in their assumed contribution to an
      increased risk of coronary heart disease (CHD). In the general population
      increased levels of lipoprotein(a) [Lp(a)] constitute an independent risk factor
      for CHD by itself as well as in combination with increased levels of cholesterol
      and low density lipoprotein (LDL)-cholesterol, respectively. Two hundred and
      fifty-six patients with 27 +/- 7 months HAART and 84 treatment-naive HIV-1
      positive patients were screened for cardiovascular risk factors. The subjective
      perception of fat wasting and/or accumulation in different sites of the body,
      which was possible to evaluate in 235 patients on HAART and 73 treatment-naive
      patients, the levels of plasma triglycerides (TG), cholesterol, LDL and high
      density lipoproteins (HDL)-cholesterol, LDL/HDL ratio and Lp(a) were measured. Of
      the patients on HAART, 42% (98/235) reported abnormal fat distribution as
      compared with 4% (3/73) of the treatment-naive patients (P<0.0001). The levels of
      TG, cholesterol and LDL-cholesterol, but not HDL-cholesterol or Lp(a) were higher
      (P<0.0001) in the HAART group as compared with the naive group. Very high Lp(a)
      levels (> 700 mg/l) were more common among HAART patients as compared with naive,
      14% (36/256) vs 2% (2/83); P=0.0022. The Lp(a) levels correlated to the levels of
      LDL-cholesterol, but not to total cholesterol, HDL-cholesterol or TG, and did not
      differ between patients with and without subjective perception of abnormal fat
      distribution. A significant number of the HAART patients had very high levels of
      Lp(a) and various combinations of increased lipid values associated with
      considerably increased risk for CHD. The elevation of Lp(a) did not relate to any
      other clinical or laboratory parameter than to LDL-cholesterol.

PMID- 10919488
TI  - Gay men in Australia who do not have HIV test results.
AB  - Whereas most gay men in Australia know their HIV test result, a consistent
      minority do not. From Gay Community Periodic Surveys (n=6831) conducted during
      1998 in the 5 largest cities, those who did not have HIV test results (13.3%
      overall) comprised 10.0% in Sydney, 15.7% in Melbourne, 13.6% in Brisbane, 15.2%
      in Perth and 14.0% in Adelaide, representing a significant difference between
      cities (P < 0.001). Gay men who did not have HIV test results differed from those
      who did in several ways. They were on average younger (31 vs 35 years, P<0.001)
      and less likely to be in professional occupations (P<0.001). They were less
      likely to identify themselves as 'gay' (P<0.001), spent less time with other gay
      men (P<0.001) and had fewer gay friends (P<0.001). They had sex with fewer
      different men 'in the previous 6 months' (P<0.001) and were more likely to be in
      a monogamous relationship or without sexual partners at the time of the survey
      (P<0.001). With respect to both regular and casual partners, they were more
      likely (P<0.001) to have 'no such partner'/'no anal intercourse' rather than
      'anal intercourse' (either always protected or sometimes unprotected). These
      differences between gay men who did and did not have HIV test results were
      confirmed in a logistic regression (apart from 'amount of free time spent with
      gay men' and 'relationship status' which were accounted for by closely correlated
      variables in the reduced logistic model). Social and sexual environment appears
      to exert an influence on HIV testing rather than sexual risk per se.

PMID- 10919489
TI  - Frequent re-infection in a community with hyperendemic gonorrhoea and chlamydia:
      appropriate clinical actions.
AB  - In a cohort of 1200 individuals experiencing an index infection of gonorrhoea or
      chlamydia in a rural North Carolina county, we studied the risk factors for re
      infection within 16 months. The occurrence of asymptomatic re-infection was
      estimated from a sample of controls. Re-infection with either of the two STDs
      occurred in one-quarter (24%) of the study participants and 22% of the controls.
      The factors associated with re-infection were age less than 25 years, African
      American race, male sex, and infection prior to the index infection. The
      behavioural and attitudinal variables tested were not associated with re
      infection. The patterns of re-infection in this study do not provide guidance for
      targeting resources toward a subgroup of the clinic population. Structuring
      clinical services to make them more available and acceptable to all potential
      clinic clients can contribute to decreasing the duration of infections. Lowering
      the community prevalence in this way will then decrease the likelihood of re
      infection rates.

PMID- 10919491
TI  - Indinavir use: associated reversible hair loss and mood disturbance.
AB  - We present the case of a 55-year-old heterosexual man who had a generalized
      alopecia and mood changes associated with the antiretroviral protease inhibitor;
      indinavir within 6 months of use. This was reversed within 3 months of change of
      therapy to the protease inhibitor, nelfinavir with demonstrable changes in his
      Hospital Anxiety and Depression (HAD) scale scores.

PMID- 10919490
TI  - Transmission of HIV from injecting drug users to their wives in India.
AB  - We aimed to identify factors associated with transmission of human
      immunodeficiency virus (HIV) from injecting drug users (IDUs) to their wives in
      Manipur, northeast India, where the prevalence of HIV among IDUs is 80% via a
      case-control study. One hundred and sixty-one HIV-infected IDUs and their wives
      were recruited from September 1996 to August 1997 inclusive. HIV status was
      determined by enzyme-linked immunosorbent assay (ELISA) plus Western blot,
      Interviews were administered anonymously. Regression analysis identified factors
      associated with transmission of HIV from IDU husbands to their non-injecting
      wives. Seventy-two wives (45%) were HIV-positive. Only 15% of the couples
      reported regular usage of condoms during intercourse. On multivariate analysis, a
      sexually transmitted disease (STD) in either member, reported by the husband,
      estimated duration of HIV in the husband for >8 years, and a history of blood
      transfusions were associated with infection in the wife. In conclusion, STDs are
      associated with transmission of HIV from husband to wife. Improved control of
      STDs, condom promotion, and improved blood screening are urgently needed in
      Manipur.

PMID- 10919492
TI  - Cutaneous cryptococcosis in two patients with acquired immunodeficiency syndrome.
AB  - We present 2 cases of systemic cryptococcosis with cutaneous involvement in
      patients with acquired immunodeficiency syndrome (AIDS). Both patients were male,
      intravenous drug abusers, 31 and 35 years old, with severe immunodepression and a
      CD4+ lymphocyte count of 10/ml and 1/ml, respectively. They both had papular
      lesions reminiscent of molluscum contagiosum and in one patient with concomitant
      systemic leishmaniasis, there were spores of Cryptococcus neoformans coexisting
      with the leishmanias in the cutaneous lesions, constituting the first reported
      case of this particular association. Both patients responded well to amphotericin
      B followed by fluconazole.

PMID- 10919494
TI  - Chlamydia trachomatis as a probable cause of prostatitis.

PMID- 10919493
TI  - Human immunodeficiency virus and syphilis seropositivity among patients attending
      clinic for sexually transmitted disease.

PMID- 10919495
TI  - Monetary incentives for sex workers.

PMID- 10919496
TI  - Zoon's balanitis and carcinoma of the penis.

PMID- 10919497
TI  - Syphilitic abdominal aortic aneurysm in a middle-aged married villager.

PMID- 10919498
TI  - Th1/Th2 lymphocyte polarization in asthma.
AB  - Asthma is a complex inflammatory disease of the lung characterized by variable
      airflow obstruction, bronchial hyperresponsiveness, and airway inflammation.
      Inflammation in asthma consists of airway infiltration by mast cells,
      lymphocytes, and eosinophils. There is accumulating evidence that CD4+
      lymphocytes with a Th2-cytokine pattern play a pivotal role in the pathogenesis
      of asthma. These cells orchestrate the recruitment and activation of the primary
      effector cells of the allergic response (mast cells and eosinophils), through the
      release of cytokines such as IL-4, IL-5, and IL-13. Allergic inflammation is also
      implicated in airway epithelium changes, although the mechanisms by which
      inflammatory cells and, in particular, T cells interact with the epithelium are
      not completely clarified. This paper explores the role of T cells in the allergic
      inflammation of asthma.

PMID- 10919499
TI  - Genetic polymorphism and clinical outcome: identification of individuals at risk
      of a poor clinical outcome.
AB  - Susceptibility and outcome in complex disorders such as asthma and cancer appear
      to be determined, at least in part, by genetic polymorphism. However, while our
      ability to identify new allelic variants and study them in case and control
      populations has greatly improved, considerable difficulties remain in elucidating
      how many genes determine particular clinical phenotypes. This is because most
      studies have concentrated on study of single genes in relatively small study
      groups. The important issues of gene-gene interactions (epistasis) and high-risk
      subgroups have not yet been adequately addressed. We now describe a general
      approach, using patients with head and neck cancers as an example. Our purpose is
      to demonstrate candidate gene selection, statistical approaches, and
      identification of patient subgroups.

PMID- 10919500
TI  - Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism
      for susceptibility and development of atopic airway inflammation.
AB  - A common feature of environmental irritants is their ability to cause local
      inflammation which could alter airway function. The principal targets of such
      injury are the epithelial cells lining the airway passages and the lower
      respiratory gas-exchange areas. While host atopy is a recognized risk factor for
      airway inflammation, atopy alone cannot cause asthma. We hypothesize that
      susceptibility to persistent airway inflammation in atopic individuals is
      characterized by an inherited deficiency in the effectiveness of detoxification
      of inhaled irritants and products of oxidative stress such as reactive oxygen
      species (ROS). Our case-control studies show that polymorphisms at the
      glutathione S-transferase, GSTP1, locus on chromosome 11q13 may account for
      variation in host response to oxidative stress, a key component of airway
      inflammation. Frequency of the GSTP1 Val/Val genotype is reduced in atopic
      subjects compared with nonatopic subjects. Trend analysis also shows a
      significant decrease of GSTP1 Val/Val (with parallel increase of GSTP1 Ile/Ile)
      genotype frequency with increasing severity of airflow obstruction/bronchial
      hyperresponsiveness. The implication of specific polymorphisms at the GSTP1 locus
      in airway inflammation is entirely novel: however, GST are recognized as a
      supergene family of enzymes critical in 1) cell protection from the toxic
      products of ROS-mediated reactions, 2) modulation of eicosanoid synthesis.

PMID- 10919501
TI  - Murine models of inflammation: role of CD23.
AB  - The role of IgE in eosinophil recruitment and bronchial hyperresponsiveness has
      been extensively studied with murine models of inflammation. Many investigators
      using various knockout models have clearly shown that both IgE-dependent and 
      independent pathways play a role in eosinophil recruitment and bronchial
      hyperresponsiveness after allergen challenge, illustrating the complexity of
      airways inflammation. The expression of this response is likely to involve many
      interacting pathways, and it will be a considerable challenge to determine key
      points within these pathways that will yield novel targets for future therapeutic
      strategies.

PMID- 10919502
TI  - Arachidonic acid metabolism in inflammatory cells of patients with bronchial
      asthma.
AB  - Over the last few years, the demonstration of beneficial effects of leukotriene
      receptor antagonists in various forms of asthma has renewed clinical and
      pharmacologic interest in this class of lipid mediators. Several studies
      demonstrated an increased biosynthesis of cysteinyl leukotrienes (CysLT) in
      asthmatic patients. However, the reasons for the dysregulated production of
      CysLTs in asthmatic patients are not completely defined. An improved method of
      lipid mediator detection and the availability of cells isolated from human
      airways (by bronchoalveolar lavage [BAL] and bronchial biopsies) have allowed
      initial studies to address this issue. Eosinophils retrieved from inflamed
      airways of asthmatics have a larger arachidonic acid (AA) content than their
      blood counterpart. The high level of AA in these cells is primarily due to a
      remodeling of endogenous arachidonate pools with the accumulation of this fatty
      acid in a triglyceride-associated pool. In addition, elevated levels of a
      secretory form of phospholipase A2, the key enzyme initiating the cascade of
      CysLTs, are found in the BAL of asthmatics. Finally, eosinophils isolated from
      the BAL of asthmatics have an increased expression of LTC4 synthase. The level of
      expression of this enzyme correlates with the increased amount of CysLTs produced
      in the airways of these patients. Taken together, these data identify at least
      two possible mechanisms to explain the excessive CysLT production in asthmatics:
      1) an increased content of AA in the glycerolipid pools of inflammatory cells 2)
      an enhanced activity of key biosynthetic enzymes involved in CysLT synthesis.

PMID- 10919503
TI  - Role of endogenous nitric oxide in asthma.
AB  - Endogenous nitric oxide (NO) is an ubiquitous signaling molecule with important
      regulatory functions such as regulation of blood pressure, neurotransmission, and
      host and immune defense. In the respiratory tract, NO is formed and released by
      various sources including endothelial and epithelial cells, nerves, airway smooth
      muscle, and inflammatory cells. Recent evidence suggests that endogenous NO is
      the neurotransmitter of the nonadrenergic noncholinergic inhibitory (iNANC)
      system, the only bronchorelaxant neural pathway of human airways. A number of
      studies also suggest that in some species epithelium-derived NO accounts for the
      functional bronchoprotective role of the so-called epithelium-derived relaxing
      factor. In human airways, endogenous NO counteracts the bronchoconstriction
      induced by pharmacologic stimuli such as bradykinin, histamine, and methacholine.
      On the basis of these and other observations, it is suggested that a reduced
      synthesis and/or activity of endogenous NO may contribute to the pathogenesis of
      airway hyperresponsiveness that characterizes asthma and other respiratory
      disorders. This short paper summarizes the activities of endogenous NO in the
      airways of experimental animals and man, and discusses the evidence supporting
      the view that NO confers bronchoprotection.

PMID- 10919504
TI  - Phenotypic features of alveolar monocytes/macrophages and IL-8 gene activation by
      IL-1 and TNF-alpha in asthmatic patients.
AB  - The alveolar macrophage (AM), a major defense cell in the lung, participates in
      immune and inflammatory reactions through the release of several regulatory and
      chemotactic cytokines. In particular, macrophages are considered to play a
      pivotal proinflammatory role in the production and maintenance of airway
      inflammation and bronchial hyperreactivity. To assess the phenotypic pattern of
      AM from asthmatic subjects, we performed the following experiments: 1)
      cytofluorometric analysis of specific phenotypic features (CD11b, CD14, CD16,
      CD45, HLA-DR, CD71, CD95, and CD44) 2) assessment of the production of tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1, and the chemotactic regulatory
      cytokine IL-8 by unstimulated and lipopolysaccharide-stimulated AM. In these
      patients, we phenotypically characterized the AM, showing their strong
      proinflammatory activity also in patients with mild asthma. Their activity has
      been clarified by our biomolecular data that showed a constitutive basal IL-8
      production by AM, and also indicated that IL-1 and TNF-alpha were able to
      upregulate the ability of activated human AM to produce IL-8 at the protein and
      messenger ribonucleic acid (mRNA) levels.

PMID- 10919505
TI  - Respiratory infections and asthma.
AB  - Clinical and experimental evidence suggests an important role for respiratory
      infections in the development of asthma attacks. Viral upper respiratory
      infections have been associated with 80% of asthma exacerbations in children and
      50% of all asthma episodes in adults. Human rhinovirus has been implicated as the
      principal virus associated with asthma episodes. Separate studies indicate that
      atypical bacteria such as Chlamydia pneumoniae and Mycoplasma pneumoniae may
      precipitate asthma symptoms. Although not completely clarified, the intricate
      pathogenetic mechanisms by which viral infections promote asthma attacks have
      been extensively investigated in recent years. By contrast, it has not yet been
      established whether atypical bacterial infections are an epiphenomenon or a
      pathogenic event in asthma.

PMID- 10919506
TI  - Mechanisms involved in airway obstruction: the role of smooth muscle.
AB  - Structural changes in the airway walls that are probably driven by mediators
      released as a consequence of chronic allergic inflammation are prominent features
      of asthma. However, it is not clear how each of the many changes that occur in
      the airway wall contribute to altered airway function in asthma. Collagen
      deposition in the subepithelial matrix, around and inside the smooth muscle,
      would be expected to oppose the effect of smooth-muscle contraction. Conversely,
      geometric factors would result in exaggerated airway narrowing for a given degree
      of smooth-muscle shortening; decreased airway wall stiffness and increased airway
      narrowing for a given amount of force generated by the smooth muscle. Degradation
      of the matrix may alter the coupling between muscle and lung recoil, allowing
      exaggerated smooth-muscle shortening. Increase in muscle mass associated with
      preservation of its contractile capacity could be the most important contributor
      to exaggerated airway narrowing.

PMID- 10919507
TI  - Asthma: pathophysiology of the bronchial obstruction.
AB  - From a pathophysiologic perspective, the changes that occur in asthma are
      multiple, diverse, and complex. Assessment of the mechanical properties of the
      ventilatory apparatus provides several different types of information, depending
      on the gravity of the bronchial obstruction. During asthma, or induced bronchial
      obstruction, the function of the muscles is altered, causing changes in
      respiratory timing. Expiratory duration decreases more than inspiratory duration,
      and the functional residual capacity (FRC) increases, due to mechanical changes
      within the airways that lead to air trapping. The related hypoventilation is
      responsible for hypoxemia and hypercapnia, but it does not severely affect the
      diffusion capacity of the alveolocapillary membrane. We describe the
      pathophysiology of the bronchial obstruction in asthmatic patients, underlining
      the critical function of the respiratory muscles. Moreover, we clarify the
      relations between the ventilatory changes and gas-exchange alteration.

PMID- 10919508
TI  - Gastroesophageal reflux disease and asthma: an intriguing dilemma.
AB  - BACKGROUND: Gastroesophageal reflux disease (GORD) is characterized by typical
      reflux symptoms and multiple atypical extraesophageal symptoms. Gastric asthma is
      a prominent extraesophageal manifestation of GORD. There is persistent debate
      about the pathophysiologic mechanisms triggering asthma by GOR. METHODS: We
      conducted a review of the literature. RESULTS: The pathogenic mechanism could be
      either a vagally transmitted reflex or an intratracheal aspiration of refluxed
      material. In both hypotheses, the role of inflammatory mediators has been
      proposed. CONCLUSIONS: Neurogenic inflammation is a good theoretic basis for a
      pathogenic interpretation of the disorder. In atopic patients, food allergy has
      been recently proposed as a possible cause of GOR and associated respiratory
      symptoms, and it should be considered in the diagnostic work-up of all patients
      with GORD.

PMID- 10919509
TI  - Use of altered peptide ligands to modulate immune responses as a possible
      immunotherapy for allergies.
AB  - Allergies are dramatically increasing in prevalence, and the management of these
      diseases is a heavy burden on the health-care systems of developed countries. In
      recent years, many efforts have been made to improve the therapy of allergies and
      to develop new approaches for immunotherapy. Here we briefly review the use of
      peptides to modulate T-cell responses to allergens. We focus mainly on the
      possibility of using altered peptide ligands (APLs), i.e., peptides tailored on
      immunodominant T epitopes and bearing a single amino-acid substitution, as a tool
      to modulate immune responses to allergens. These peptides may be recognized by
      the specific T cells triggered by the agonist peptides, but they are unable to
      elicit T-cell responses; thus, they could be ideal candidates to modulate immune
      responses to allergens. The availability of these peptides could allow new
      approaches for immunotherapies.

PMID- 10919510
TI  - New perspectives in asthma treatment.
AB  - The recent advances in the knowledge of the basic mechanisms underlying asthmatic
      inflammation have significantly contributed to the delineation of new therapeutic
      perspectives for asthma. There are currently three main approaches to the
      development of novel antiasthma treatments: 1) improvement in existing classes of
      drugs 2) identification of new compounds able to interfere with the complex
      network of proinflammatory mediators, cytokines, chemokines, and adhesion
      molecules involved in the pathogenesis of asthma 3) utilization of new forms of
      immunotherapy aimed at blocking the unbalanced Th2 response which characterizes
      the pathophysiology of asthma. Such a remarkable expansion in available
      therapeutic options will probably allow us, over the next decade, to treat asthma
      by more selectively targeting the pathogenetic events responsible for this
      widespread airway disease.

PMID- 10919511
TI  - The search for essential genes.
AB  - The bacterial genomic era began with the publication of the chromosomal sequence
      of Haemophilus influenzae. As few of the observed genes had been examined
      experimentally, functional assignments were made by comparative analysis and for
      many genes no annotation could be made. This mini-review briefly describes the
      genomic-scale experimental approaches being used to identify genes required for
      the growth of microorganisms. Identifying 'essential genes', the simplest
      possible annotation for the unknown open reading frames, is important for
      antibacterial and antifungal research and is a first step to defining the minimum
      functional requirement for autonomous growth.

PMID- 10919512
TI  - Two distinct ospA genes among Borrelia valaisiana strains.
AB  - Borrelia valaisiana is a recently described bacterial species in the Borrelia
      burgdorferi sensu lato complex. To further characterize this bacterium, the
      plasmid-encoded ospA genes from eight B. valaisiana isolates were amplified by
      PCR, cloned and sequenced. All B. valaisiana isolates studied possessed an ospA
      gene with a size of 822-825 bp. The identity of the predicted amino acid
      sequences of the OspA proteins among B. valaisiana isolates was 69.1-100%, and
      ranged from 68.2 to 79.1% between B. valaisiana and other B. burgdorferi sensu
      lato species. Based on the OspA protein sequences, the eight B. valaisiana
      isolates could be distinguished into two subgroups. Subgroup I contained six B.
      valaisiana isolates of which OspA sequences were almost identical, but clearly
      differed from other LB spirochetes. Subgroup II consisted of two isolates with
      identical OspA sequences which were only 70% identical to subgroup I B.
      valaisiana isolates and similarly distant from the OspA sequences of other B.
      burgdorferi sensu lato genospecies. Phylogenetic analysis indicates that B.
      valaisiana isolates belonging to subgroups I and II possibly evolved from two
      distinct ancestors. Our data showed for the first time a major difference in OspA
      proteins within a well-defined B. burgdorferi sensu lato species at the
      evolutionary level, suggesting that it is not always reliable to assign Borrelia
      isolates to a definite species solely based on data from ospA gene sequence
      analysis.

PMID- 10919513
TI  - Interest of partial 16S rDNA gene sequences to resolve heterogeneities between
      Leptospira collections: application to L. meyeri.
AB  - This paper describes the advantage of using the first 330 bp (positions 46 to
      375, Escherichia coli numbering) of the 16S rDNA gene for comparison of
      Leptospira isolates. Phylogenetic analysis conducted from the whole 16S rDNA
      sequences available in databanks as well as that conducted from the partial
      sequences yielded quite similar results, in accordance with data inferred from
      previous DNA-DNA relatedness studies. This tool was used for the comparison of
      Leptospira strains from different reference collections. Consistent results were
      obtained from the analysis of the polymorphism generated by pulsed-field gel
      electrophoresis. The study focused on different serovars of L. meyeri species,
      the classification of which has been controversial. The results revealed large
      collection heterogeneities, and suggest that the classification of the L. meyeri
      species should be revised.

PMID- 10919514
TI  - Usefulness of IS6110-restriction fragment length polymorphism typing of Brazilian
      strains of Mycobacterium tuberculosis and comparison with an international
      fingerprint database.
AB  - Strains of Mycobacterium tuberculosis isolated from 219 different tuberculosis
      patients, 115 from patients residing in Rio de Janeiro, 79 from Rio Grande do Sul
      and the remaining from other regions of the country, were analyzed by IS6110
      restriction fragment length polymorphism fingerprinting. The IS6110-DNA patterns
      from these strains were highly polymorphic: 174 different patterns were observed
      and 25 patterns were shared by 70 isolates (32%). Most strains (93.4%) had
      multicopy patterns and only 17% of clustered strains had less than six IS6110
      copies. Strain clustering was significantly higher for isolates from Rio Grande
      do Sul (36.7%) in comparison with strains from Rio de Janeiro (22.6%), but only
      when using high stringency during cluster analysis. Upon screening of an
      international database containing 3,970 fingerprints of M. tuberculosis strains,
      15% of the patterns of Brazilian strains (21% of the strains) were identical to a
      fingerprint of an isolate from another country and one particular eight-band
      pattern forming the largest Brazilian cluster was detected in seven additional
      countries, suggesting that international transmission of tuberculosis from and to
      Brazil could be occurring frequently. Alternatively,preferential use of certain
      IS6110 integration sites could also be important in high-copy number strains,
      having important consequences for the use of databases for epidemiological
      studies on a large scale.

PMID- 10919516
TI  - On the fate of ingested Bacillus spores.
AB  - Spores of various Bacillus species, including B. subtilis, B. cereus and B.
      clausii, are used as probiotics, although they are generally absent from the
      normal microflora of man. We used two nonpathogenic Bacillus species, B. subtilis
      and B. clausii, to follow the fate of spores inoculated intragastrically in mice.
      We did not find detectable amounts of vegetative cells in intestinal samples,
      probably because of high toxicity of the conjugated bile salt taurodeoxycholic
      acid against Bacillus species. Both spores and cells were detected in the lymph
      nodes and spleen of one mouse. Our results indicate that Bacillus is present in
      the intestinal tract solely as spores and that nonpathogenic Bacillus spores may
      germinate in lymphoid organs, a finding reminiscent of B. anthracis germination
      in macrophages. These results indicate that any claimed probiotic effect of B.
      subtilis should be due to spores or, alternatively, to vegetative growth outside
      the intestine.

PMID- 10919515
TI  - Optimization of green fluorescent protein expression vectors for in vitro and in
      vivo detection of Listeria monocytogenes.
AB  - The green fluorescent protein (GFP) of the jellyfish Aequorea victoria is a
      useful reporter molecule for monitoring in vivo gene expression in eukaryotic and
      prokaryotic cells. We constructed a series of GFP vectors for in situ detection
      of the intracellular pathogen Listeria monocytogenes. The gfp-mutl gene, which
      encodes a red-shifted GFP, was transcriptionally fused to a strong L.
      monocytogenes promoter and inserted into various Escherichia coli-Listeria
      shuttle vectors: i) the integrative monocopy plasmid pAT113; ii) the low copy
      number plasmid pTCV-Exl; iii) the high copy number plasmid pAT18. Listeria cells
      harboring pNF6 and pNF7, constructed from pAT113 and pTCV-Exl, respectively, gave
      low fluorescence intensities, and were optically detected in cultured
      macrophages, but not in tissue sections. The fluorescence of Listeria with the
      pAT18 derivative pNF8 was about 40 times greater than that with pNF6 and 15 times
      greater than that with pNF7. Listeria cells harboring pNF8 were readily detected
      in both cultured macrophages and tissue sections. Constructed GFP vectors did not
      affect the virulence of L. monocytogenes in a murine model of infection.

PMID- 10919517
TI  - Diversity of Paenibacillus polymyxa strains isolated from the rhizosphere of
      maize planted in Cerrado soil.
AB  - Paenibacillus polymyxa populations present in the rhizosphere of maize (cultivar
      BR-201) planted in Cerrado soil were investigated in order to assess their
      diversity at four stages of plant growth. A total of 67 strains were isolated and
      all strains were identified as P. polymyxa by classical biochemical tests, API
      50CH tests and a set of species-specific primers based on the 23S rDNA sequence.
      To compare the isolated strains, phenotypic characteristics (utilization of
      different carbohydrates, resistance to antibiotics and production of
      antimicrobial substances) and genetic approaches (hybridization with a Klebsiella
      pneumoniae nifKDH probe and BOX-PCR) were used. Fermentation of glycerol,
      arabinose, xylose and rhamnose varied among the isolates and these data divided
      the strains into five groups. Fifty strains (75%) showed homology to plasmid
      pSA30 (containing the nifKDH genes) resulting in five different hybridization
      patterns. Using BOX-PCR, 18 groups were observed. Phenetic analyses were applied
      based on the unweighted pair group method with arithmetic means using the
      phenotypic and genetic data, separately. All P. polymyxa isolates could be
      divided into two main clusters at approximately 52% and into 18 groups at
      approximately 89% of similarity, when phenotypic data were used. Also, two main
      clusters were formed at 65% of similarity when genetic data were used. In this
      dendrogram, clusters were further split into 10 and 22 groups, at about 88 and
      97% of similarity, respectively. Finally, all phenotypic and genetic data, or
      just the genetic data, were used in a multivariate analysis of variance (MANOVA)
      in order to address the heterogeneity among P. polymyxa populations during the
      different stages of maize growth. The resulting data showed that strains isolated
      10, 30, 60 and 90 days after maize sowing were statistically different.

PMID- 10919518
TI  - Development of biocatalysts carrying naphthalene dioxygenase and dihydrodiol
      dehydrogenase genes inducible in aerobic and anaerobic conditions.
AB  - We developed biocatalysts carrying naphthalene dioxygenase and dihydrodiol
      dehydrogenase genes cloned from plasmid pN3 of Pseudomonas fluoresceins N3
      involved in naphthalene degradation, as an alternative approach to the production
      of hydroxylated compounds by chemical synthesis. Naphthalene dioxygenase is
      responsible for hydroxylation of the hydrocarbon into the corresponding 1,2
      dihydro-1,2-dihydroxy derivative and dihydrodiol dehydrogenase is involved in the
      subsequent transformation into the 1,2-dihydroxy derivative. The first reaction
      strictly requires the presence of oxygen, essential for the dioxygenation
      reaction, while the second one can also be performed in anaerobic conditions that
      are optimal to avoid the easy oxidation of bioconversion products. Consequently,
      we constructed biocatalysts carrying the genes responsible for the
      biotransformation of hydrocarbons, inducible under aerobic and anaerobic
      conditions. We cloned the dioxygenase gene under its promoter, inducible by
      salicylic acid and the dihydrodiol dehydrogenase under the Pnar promoter of
      Escherichia coli, inducible by nitrate, in a nitrogen atmosphere, in order to
      develop biological systems with the possibility of controlling the expression of
      the cloned genes by the shift from aerobic to anaerobic conditions. Bioconversion
      experiments performed in aerobic conditions showed dihydrodiol production and
      dehydrogenase repression; as soon as cultures were switched to nitrogen,
      dihydrodiol dehydrogenation with an efficient production of 1,2
      dihydroxyderivatives was observed.

PMID- 10919519
TI  - Injury hospitalizations before and after the 1994 Northridge, California
      earthquake.
AB  - This study compared hospital-admitted injuries during the 14 days after the
      Northridge, California, earthquake of January 17, 1994, with hospital-admitted
      injuries during the preceding 16 days at the same facilities. Seventy-eight
      hospitals providing emergency care in Los Angeles County were screened; 16 were
      identified as having admitted at least one person for an earthquake-related
      injury. Retrospective chart reviews of hospitalized injuries for all of January
      1994 were conducted at those facilities. The Northridge earthquake resulted in
      138 injuries severe enough to require hospitalization. On the day of the
      earthquake, such injuries were 74% more frequent than usual overall. Some
      hospitals experienced as many as five times the number of injury admissions seen
      in the days preceding the event. The increase in caseload was short-lived,
      however; injury admissions tended to return to normal levels within two days
      after the quake. Previous reported estimates of the overall number of severe
      injuries caused by the Northridge earthquake appear to be exaggerated.

PMID- 10919520
TI  - Implementation of a disease-specific care plan changes clinician behaviors.
AB  - The study objective was to determine the impact on quality of care, resource use,
      and outcomes by developing an emergency department (ED)-based asthma-specific
      care plan. The design was a time based, prospective cohort and set at an urban
      university/trauma center, EM residency site, combined adult/pediatric department.
      Best practice was defined prospectively for ED asthma patients, leading to an
      asthma care plan (ACP). Triage nurses were instructed to begin use of ACP when
      patients presented with asthma as the primary complaint. Charts of all patients
      diagnosed with asthma during 3-month study period were retrospectively reviewed
      against predefined outcomes. Results were analyzed with chi2 or student's t
      tests. After ACP introduction, the timeliness of beta agonist treatments (three
      beta agonist treatments within 90 minutes; 86% versus 63%, P < .05) and ED length
      of stay (LOS) (3.39 +/- 1.88 hrs versus 3.87 +/- 2.12 hrs, P < .05) improved.
      After introduction of ACP, only 55% of patients diagnosed with asthma had care
      documented on the ACP (ACP+ group). ACP+ group had more timely beta agonist
      treatment (93% versus 74%, P < .01), shorter LOS (3.29 +/- 1.90 vs. 3.53 +/- 1.86
      hrs, P < 0.5) more appropriate steroid dosages (67% versus 41%, P < .01), and
      fewer tests (41% versus 59%, P < .05). No improvements were noted in admission or
      relapse rates. In conclusion, care plans can improve quality of care and decrease
      LOS, but may have limited impact on outcomes of admission/discharge or relapse
      rates.

PMID- 10919521
TI  - Comparison of men and women presenting to an ED with acute appendicitis.
AB  - Appendicitis is a common problem presenting to the Emergency Department (ED).
      Missed or delayed diagnosis can result in increased morbidity and is a common
      cause of malpractice claims. Diagnosis in women is more difficult because of
      additional clinical considerations. The study hypothesis is that women with
      appendicitis presenting to an ED experience a longer delay to operative
      intervention resulting in an increased rate of perforated appendix. A
      retrospective chart review of 196 male and female patients between twelve and
      fifty years of age presenting to the ED with final discharge diagnosis of
      appendicitis was performed. Mean time from ED presentation to operative
      intervention was 477 minutes for men and 709 minutes for women (P = .02).
      Perforated appendix was present in 38.7% of men and 23.5% of women (P = .002).
      Women with appendicitis presenting to an ED experience significant delay to
      surgery, however, this is not associated with an increased rate of perforation.

PMID- 10919522
TI  - Patient preferences regarding pain medication in the ED.
AB  - Previous studies have reported inadequate pain control in the emergency
      department (ED). The primary purpose of this study was to determine the
      proportion of ED patients with acute fractures who actually wanted pain
      medication given in the ED. A convenience sample of 107 adults with acute long
      bone fractures seen in a community hospital ED were surveyed on the pain level
      they had on ED presentation, the pain level desired at ED discharge, and their
      preferences for administration of analgesia in the ED. Eighty-eight percent of
      the patients wanted pain medication given in the ED and 77% actually received it.
      Sixty-nine percent were comfortable with a nurse administering pain medication
      before physician evaluation. Seventy percent wanted pain control without being
      sedated and 25% wanted complete pain relief even if sedation was necessary to
      achieve it. Sixty percent were either slightly concerned or not concerned about
      potential medication side effects.

PMID- 10919524
TI  - Changes in contused lung volume and oxygenation in patients with pulmonary
      parenchymal injury after blunt chest trauma.
AB  - Although it is well known that pulmonary parenchymal injury impairs oxygenation,
      the relationship between hypoxemia and volume of the contused lung after blunt
      chest trauma remains unknown. We studied 23 blunt chest trauma patients who
      underwent thoracic computed tomography (CT) within 24 hours after admission and
      also underwent follow-up CT at 1-week intervals until abnormal lung findings
      disappeared. Contused lung volume was determined quantitatively by CT. CT
      findings of parenchymal injury were either a diffuse lesion that disappeared
      within 1 week (n = 9 patients, group 1), or a solitary lesion that remained a few
      weeks after resolution of the diffuse lesion (n = 14 patients, group 2).
      PaO2/FiO2 was positively correlated with the volume of contused lung during the
      first 24 hours in both groups, however, there was no significant correlation
      after 1 week after injury. Degree of impaired oxygenation is related to the
      volume of the diffuse lesion that is recognized soon after injury.

PMID- 10919523
TI  - Changes in chest electrode impedance.
AB  - The Prehospital Defibrillation Program in Singapore has in some cases shown a
      lower amplitude of ventricular fibrillation (VF) than considered the norm. The
      electrode skin impedance (ESI) refers to the skin impedance determined between
      two electrodes placed at specific positions on the body surface. The objective of
      this prospective study was to measure the ESI of patients at 5 Hz and 2 kHz
      frequencies, and assess its change with time from the application of electrodes,
      the difference between the ESI at two different sets of electrode placement
      positions, and correlation with patient factors. Patients who were 25 years or
      older and not critically ill had their ESI measured with a modified Heart-Save
      911 defibrillator, using signal frequencies at 5 Hz and 2 kHz, at 10 seconds, 1
      and 2 minutes after electrodes application. Two sets of positions were used;
      position 1 where an electrode is placed in the right subclavicular region and
      another just lateral to the apex beat on the left and position 2, which
      represents the mirror-image of position 1. Thirty-six each of men and women
      patients were studied. The mean age and weight were 59.9 +/- 13.5 years and 56.8
      +/- 24.1 kg respectively. There was no significant correlation between the ESI
      and patients' body weight or sex. However, there was a significant decrease in
      the ESI with time from application of electrodes at both positions (P < .05) with
      the two different frequencies. The ESI was lower when measured at lower
      frequencies and higher when taken at higher frequencies, but there was no
      statistically significant difference between the two mirror-image positions used.
      Thus, with lower frequency, the electrocardiogram amplitude of VF recorded on the
      automated external defibrillator could be enhanced.

PMID- 10919525
TI  - Unrecognized medical emergencies admitted to psychiatric units.
AB  - Alteration of mental status secondary to medical illness may occasionally be
      incorrectly attributed to a psychiatric problem. The cases of 64 patients with
      unrecognized medical emergencies inappropriately admitted to psychiatric units
      from emergency departments were reviewed to determine the cause of the
      misdiagnoses. Medical diagnoses most often missed included severe intoxication
      with alcohol or other illicit substance (34.4%), drug or alcohol withdrawal or
      delirium tremens (12.5%), and prescription drug overdose (12.5%). In none of the
      cases (0%) was an appropriate mental status examination performed. Other common
      causes of misdiagnosis included inadequate physical examination (43.8%), failure
      to obtain indicated laboratory studies (34.4%), and failure to obtain available
      history (34.4%). A systematic approach is required for patients with altered
      mental status, including those with psychiatric presentations.

PMID- 10919526
TI  - Determinants of patient satisfaction in a large, municipal ED: the role of
      demographic variables, visit characteristics, and patient perceptions.
AB  - We investigated predictors of patient satisfaction in a large, municipal
      emergency department (ED). Patients were telephoned 10 days postvisit, and
      satisfaction was assessed using a structured survey with 22 items measuring
      several domains, as well as the estimated length of stay. The dependent variables
      consisted of ratings of overall satisfaction and likelihood of recommending the
      ED to others. Data were obtained from 437 (38.7%) patients. Univariate statistics
      revealed strong relations between indicators of perceived care and both dependent
      variables, with weaker and mixed findings pertaining to demographics and visit
      characteristics. The final logistic regression predicting overall satisfaction
      included the following items (P < .05): degree to which staff cared for the
      patient as a person, perceptions of safety, understandability of discharge
      instructions, nurse's technical skills, and satisfaction with wait for physician.
      Likelihood to recommend was associated with (P < .05): degree to which staff
      cared for the patient as a person, understandability of discharge instructions,
      perceptions of safety, age, and insurance status. Patients' perceptions of care,
      rather than demographics and visit characteristics, most consistently predicted
      satisfaction. However, differences were observed between the specific predictors
      for overall satisfaction and likelihood to recommend, providing a possible
      explanation for inconsistencies observed in the literature.

PMID- 10919527
TI  - The comparative accuracy of radiolucent foreign body detection using
      ultrasonography.
AB  - The purpose of this prospective study was to determine the accuracy of
      ultrasonography in detecting radiolucent foreign bodies and to compare the
      performance of three newly trained emergency physicians with two experienced
      ultrasound technologists and one radiologist. One hundred-four chicken thighs
      were penetrated with a needle-driver, half of them embedded with a 1.5 cm
      toothpick. An 8.0 MHZ linear array ultrasound probe was used to detect the
      presence or absence of the foreign body. The overall accuracy (95% confidence
      interval [CI]) was 82% (79, 85); sensitivity 79% (74, 83), specificity 86% (82,
      90), positive predicative value (PPV) 85% (81, 89), and negative predicative
      value (NPV) 80% (76, 84). The accuracy (95% CI) of the radiologist was 83% (75,
      90); of the ultrasound technologists was 85% (80, 90); and of the emergency
      physicians was 0% (76, 85). The difference in accuracy among the three types of
      personnel was not statistically significant. Ultrasonography is an accurate
      modality in detecting radiolucent foreign bodies. Emergency physicians can be
      trained to provide a degree of accuracy comparable with more experienced
      ultrasonographers.

PMID- 10919528
TI  - Ketorolac versus meperidine: ED treatment of severe musculoskeletal low back
      pain.
AB  - The study objective was to assess the efficacy and patient acceptance of
      ketorolac as an alternative to meperidine for the treatment of severe
      musculoskeletal low back pain (LBP). A double blinded prospective trial in a
      convenience sample of patients >18 years of age presenting to an urban university
      hospital emergency department (ED) was conducted over a 19-month period. Patients
      were included if the pain was musculoskeletal in origin and was severe enough to
      warrant parenteral analgesics. Patients were randomized to receive 1 mg/kg
      meperidine intramuscularly (IM) or 60 mg ketorolac IM. Pain intensity was
      measured preadministration and at 60 minutes via a 100 mm Visual Analog Scale
      (VAS). Outcomes measured at 60 minutes were pain intensity decrease (PID),
      patient satisfaction, rescue analgesia requirement, sedation level, and adverse
      effects. Clinically significant pain reduction was defined as a PID of at least
      13 mm or a reduction in pain of least 30%. One hundred fifty-five patients were
      enrolled (meperidine = 75, ketorolac = 80) and 153 patients completed the study.
      At 60 minutes the mean PID was 7 mm less in the ketorolac group (95% confidence
      interval [CI] - 15 mm to 2.6 mm). Pain reduction of at least 30% occurred in 63%
      of the ketorolac group versus 67% of the meperidine group (95% CI, odds ratio
      [OR] .43 to 1.61). Rescue analgesia was required in 35% of the ketorolac group
      versus 37% of the meperidine group (95% CI, OR .47 to 1.74). Patient satisfaction
      was less in the ketorolac group (ketorolac 68% satisfied versus meperidine 74%
      satisfied) however this was not significant (95% CI, OR .66 to 2.72). Sedation
      level and adverse effects were significantly greater in the meperidine group.
      Ketorolac shows comparable single dose analgesic efficacy to a single moderate
      dose of meperidine with less sedation and adverse effects in an ED population
      with severe musculoskeletal LBP. The trend for greater pain reduction and patient
      satisfaction with meperidine needs further investigation.

PMID- 10919529
TI  - Ultrasound availability in the evaluation of ectopic pregnancy in the ED:
      comparison of quality and cost-effectiveness with different approaches.
AB  - The liberal use of ultrasonography has been advocated in patients with first
      trimester cramping or bleeding to avoid misdiagnosis of ectopic pregnancy in the
      emergency department (ED). The cost-effectiveness of different approaches to
      ultrasound availability has not been previously reported. In this study, we
      investigated measures of quality and cost-effectiveness in detecting ectopic
      pregnancy in the ED over a 6-year period, divided into three approximately equal
      epochs with three distinct approaches to ultrasound availability. The study
      retrospectively identified 120 cases of ectopic pregnancy seen in the ED over 6
      years. There was significant improvement in the percentage of patients with
      ectopic pregnancy who were documented to have absence of intrauterine pregnancy
      (IUP) at the first visit from 76% during Epoch 1, when there was limited
      availability of ultrasound through medical imaging (MI Sono), to 88% in Epoch 2,
      when MI Sono was readily available, to 96% in Epoch 3, when both MI Sono and
      ultrasound by emergency physicians (ED Sono) were readily available (P = .02).
      The estimated number of MI Sonos ordered by emergency physicians in patients at
      risk for ectopic pregnancy increased from 5.2 per ectopic pregnancy in Epoch 1 to
      11.8 per ectopic pregnancy in Epoch 2, and declined to 5.5 per ectopic pregnancy
      in Epoch 3, when 19.9 ED Sonos per ectopic pregnancy were also done. The cost of
      ED Sono in Epoch 3 was more than offset by savings from avoiding calling in
      ultrasound technicians after regular medical imaging department hours. The
      specificity of ED Sono in ruling in an IUP was 100% (95% CI 98.3 to 100%), but
      analysis of secondary quality indicators reflecting times from first ED visit to
      treatment in Epoch 3 raised the possibility that an adnexal mass or signs of
      tubal rupture may have been missed on some ED Sonos. We conclude that increased
      availability of ultrasonography leads to improved quality in the detection of
      ectopic pregnancy in the ED, but at the expense of a disproportionate increase in
      the number of ultrasound studies done per ectopic pregnancy detected. Our study
      suggests that the most cost-effective strategy is for emergency physicians to
      screen all patients with first trimester cramping and bleeding with ED Sonos, and
      to obtain MI Sonos at the time of the initial ED visit in all cases in which the
      ED Sono is indeterminate or shows no IUP.

PMID- 10919530
TI  - Hypothermic cardiac arrest: an 11 year review of ED management and outcome.
AB  - The purpose of this study was to examine the emergency department (ED) management
      of hypothermic cardiac arrest and its outcome. The medical records of all
      patients with hypothermic cardiac arrest treated in the ED from January 1, 1988
      to January 31, 1999 were retrospectively reviewed. Data collected included
      initial body temperature, serum potassium, methods of rewarming, return of
      perfusing rhythm, and morbidity and mortality. Data were analyzed by descriptive
      methods. Eleven patients were treated in the ED resuscitation room for
      hypothermic cardiac arrest. Six patients were found in cardiac arrest in the
      field, one patient arrested during transport, and four patients arrested after ED
      arrival. The average initial temperature was 79.1 degrees F (range 69.0 degrees F
      to 86.7 degrees F). Seven patients received an ED thoracotomy with internal
      cardiac massage and warm mediastinal irrigation. Four patients had airway
      management in the ED and then direct transport to the operating room for cardiac
      bypass rewarming. Three of the seven patients who received an ED thoracotomy
      subsequently went to intraoperative cardiac bypass rewarming. Five of the seven
      (71.4%) patients who received an ED thoracotomy survived, versus none of the four
      patients (0%) who went directly to intraoperative cardiac bypass. A direct
      comparison of immediate ED thoracotomy versus intraoperative cardiac bypass
      without ED thoracotomy is cautiously made as this was an unmatched and
      nonrandomized study. Three of the surviving patients underwent intraoperative
      cardiac bypass rewarming after receiving an ED thoracotomy. In two of these
      patients a perfusing rhythm had been established after thoracotomy in the ED and
      before transport to the operating room for cardiac bypass. Only one of seven
      (14.3%) patients who arrested prehospital survived versus four of four (100%) who
      arrested in the ED. ED thoracotomy with internal cardiac massage and mediastinal
      irrigation rewarming is effective in the management of hypothermic cardiac
      arrest.

PMID- 10919531
TI  - A demonstration of instant pocket wireless CT teleradiology to facilitate stat
      neurosurgical consultation and future telemedicine implications.
AB  - To show the feasibility of wireless pocket teleradiology, brain computed
      tomography scan images of five neurosurgical emergency cases were received on a
      pocket computer via a wireless modem link. Viewing times from turning on the
      pocket computer to viewing the entire image ranged from 4 to 6 minutes. The
      quality of the images was satisfactory. Reliability in obtaining a wireless
      internet connection was good, but not perfect. Wireless pocket telemedicine
      devices carried by specialists may improve the ability of telemedicine systems to
      gain access to the expertise of specialists.

PMID- 10919532
TI  - The accuracy of pulse oximetry in the emergency department.
AB  - The objective of this retrospective study was to identify factors affecting the
      accuracy of pulse oximetry in the ED. Over a 3-year period, 664 consecutive
      emergency department (ED) patients had simultaneous arterial blood gas (ABG) and
      pulse oximeter readings taken. Pulse oximeter saturations (SpO2) were compared
      with ABG CO-oximeter saturations (SaO2) for accuracy. Multiple variables
      including age, sex, hemoglobin, bicarbonate, pH, and carboxyhemoglobin (COHb)
      were analyzed to see if they affected SpO2 accuracy. ROC curves were used to
      determine the best pulse oximeter threshold for detecting hypoxia. Using
      multivariate analysis, COHb was the only statistically significant factor
      affecting the accuracy of pulse oximetry. In patients with COHb <2%, SpO2
      overestimated SaO2 by more than 4% in 8.4% of cases. In patients with COHb > or =
      2%, SpO2 overestimated SaO2 by more than 4% in 35% of cases. The best pulse
      oximetry threshold for detecting hypoxia is 92%. At this threshold, if COHb is
      <2%, pulse oximetry has a sensitivity of 0.92 and specificity of 0.90. If COHb is
      > or =2%, sensitivity is 0.74 and specificity is 0.84. For patients likely to
      have a COHb < 2, pulse oximetry is an effective screening tool for detecting
      hypoxia. However, more caution must be exercised when using pulse oximetry in
      patients likely to have a COHb > or = 2%.

PMID- 10919533
TI  - Estimation of central venous pressure by ultrasound of the internal jugular vein.
AB  - This article describes a simple, new technique using ultrasound (US) to estimate
      central venous pressure (CVP). The sonographic patterns of the internal jugular
      vein (IJV) with a low, normal, and elevated CVP are also described. Although
      bedside visual inspection of the height of the jugular veins as an estimate of
      CVP has been an integral part of the physical examination, its major limitation
      has been that the jugular veins are not always observable. In obese patients, a
      layer of fat often obscures the jugular pulsations. US has proven to be a
      powerful tool to noninvasively visualize neck veins in the emergency department.
      Bedside US of the IJV, performed by emergency physicians, provides immediate,
      important information that cannot be obtained without invasive catheters.

PMID- 10919534
TI  - Cardiac pacemakers: evaluation and management of malfunctions.
AB  - The emergency physician may be called on at any time to evaluate a patient with a
      pacemaker. Although current models are very reliable, malfunctions occur. This
      review discusses the basic components of the antibradycardic pacemaker, which
      malfunctions can be expected to occur, and how to evaluate an improperly
      functioning unit. In addition, recommendations for disposition are discussed.

PMID- 10919535
TI  - Spiral CT diagnosis of pulmonary embolus.
AB  - With the advent of new diagnostic techniques such as the spiral computed
      tomography angiogram, the sequence of tests needed to diagnose a pulmonary
      embolus may be more efficient if the testing behavior is tailored to the
      patient's underlying cardiopulmonary status. This may be particularly important
      if the patient is elderly or has other reasons for limited cardiopulmonary
      reserve. We report several cases with a new sequence of testing behavior.

PMID- 10919536
TI  - Early detection of ectopic pregnancy visualizing the presence of a tubal ring
      with ultrasonography performed by emergency physicians.
AB  - Early diagnosis of ectopic pregnancy (EP) continues to be problematic for
      emergency physicians. With the increasing availability of endovaginal
      ultrasonography (EVS) for emergency physicians, recognizing additional EVS
      findings, ie, the presence of a tubal ring, in patients with risk factors or
      clinical presentation for EP can assist the emergency physician in diagnosing EP.

PMID- 10919537
TI  - Accuracy of ED sonography in the diagnosis of acute appendicitis.
AB  - The objective was to compare the accuracy of abdominal sonography performed by
      emergency physicians in the diagnosis of acute appendicitis with that of the
      surgeons' clinical impression. Three hundred-seventeen patients with right lower
      abdominal pain admitted to the Department of Emergency Medicine at National
      Taiwan University Hospital in Taipei, Taiwan were prospectively included in this
      study. Patients were divided into two groups according to the time of day they
      visited the emergency department. Those patients visiting the emergency
      department during the day were included in group I and those during the night
      were in group II. Group I was diagnosed by sonography. Group II was diagnosed by
      surgeons' clinical impression without sonographic examination. The definitive
      diagnosis of acute appendicitis was confirmed by the pathological reports. In the
      diagnosis of acute appendicitis, group I had a sensitivity of 96.4%, a
      specificity of 67.6%, a positive predictive value of 89.8%, a negative predictive
      value of 86.2%, and an accuracy of 89.1%, and group II had a sensitivity of
      86.2%, a specificity of 37.0%, a positive predictive value of 74.6%, a negative
      predictive value of 55.6%, and an accuracy of 70.6%. The overall accuracy of
      sonography performed by emergency physicians in the diagnosis of acute
      appendicitis was superior to that of the surgeons' clinical impression.

PMID- 10919538
TI  - Wide QRS tachycardia refractory to pharmacologic interventions and cardioversion.
AB  - The case of a 43-year-old man with an idiopathic wide QRS tachycardia resistant
      to adenosine, lidocaine, procainamide, and multiple electric shocks is described.
      The tachycardia eventually stopped after a pacing wire was introduced in the
      right ventricle, inducing a run of rapid ventricular tachycardia. The possible
      causes of resistance to medications and cardioversion, and alternative treatment
      modalities are reviewed.

PMID- 10919539
TI  - Hypophosphatemia in the emergency department therapeutics.
AB  - Although hypophosphatemia is relatively uncommon, it may be seen in anywhere from
      20% to 80% of patients who present to the ED with alcoholic emergencies, diabetic
      ketoacidosis (DKA), and sepsis. Severe hypophosphatemia, as defined by a serum
      level below 1.0 mg/dL, may cause acute respiratory failure, myocardial
      depression, or seizures. Because hypophosphatemia is not as often treated by ED
      physicians, becoming familiar with a single intravenous phosphate solution and
      specific guidelines for phosphate repletion are essential. One mL of the most
      commonly available phosphate solution (K2PO4) contains 4.4 meq of potassium and 3
      mmol (93 mgs) of phosphate. Administering K2PO4 at a rate of 1 mL per hour is
      almost always a very safe and appropriate treatment for hypophosphatemia. This
      article provides guidelines for phosphate therapy in hypophosphatemic ED patients
      including those in DKA, those presenting with alcohol-related complaints
      including alcoholic ketoacidosis and patients with acute exacerbation of asthma
      and chronic obstructive pulmonary disease.

PMID- 10919540
TI  - Termination of acute wide QRS complex atrial fibrillation with ibutilide.
AB  - Ibutilide is a Vaughan-Williams class III antiarrhythmic agent approved for
      chemical cardioversion of acute onset atrial fibrillation/flutter. Emergency
      physicians rarely use ibutilide despite its proven clinical value. We report a
      case of successful chemical cardioversion using ibutilide in a patient with
      atrial fibrillation and delayed ventricular depolarization (wide QRS complex). We
      recommend that ibutilide be considered for wider use in the emergency department
      and that further studies be conducted.

PMID- 10919541
TI  - Adult and pediatric CPR: attitudes and expectations of health professionals and
      laypersons.
AB  - Nationally accepted resuscitation courses offer few guidelines for terminating
      unsuccessful cardiopulmonary resuscitation (CPR). Data were collected from 305
      physicians and nurses in 1988/1989 and 401 physicians, nurses, and laypersons in
      1998/1999 to assess their attitudes and expectations about adult and pediatric
      CPR. Respondents felt pediatric CPR efforts should continue longer than adult CPR
      efforts. Respondents in 1998/1999 felt CPR efforts did not need to continue as
      long as the 1988/1989 respondents felt. Laypersons thought that 52% of adult CPRs
      and 63% of pediatric CPRs were successful. Although lower than laypersons'
      expectations, health care professionals' expectations of CPR success were also
      unrealistic; physicians believed 24% of adult and 41% of pediatric CPRs were
      successful and nurses believed 30% of adult and 45% of pediatric CPRs were
      successful. Health care professionals also indicated that they had a clearer idea
      of when to terminate adult CPR than pediatric CPR.

PMID- 10919542
TI  - Out-of-hospital resuscitation in Tartu: effect of reorganization of Estonian EMS
      system.
AB  - The objective of this study was to evaluate the effect of reorganization of
      Estonian emergency medical services (EMS) system. The outcomes of out-of-hospital
      resuscitation in the Tartu urban area were investigated during the 6-year study
      period. The main aim of reorganization was to provide rapid access to early
      defibrillation with simultaneous advanced cardiac life support (ACLS) procedures
      on the scene. The changes were implemented since summer 1994 in Tartu at first.
      Quick availability of a mobile intensive care unit for high-risk calls;
      implementation of standards for resuscitation, and routine systematic, realistic,
      compulsory ACLS training for all ambulance staff were established. There were 368
      out-of-hospital resuscitations. Comparison of periods before and after basic
      reorganization of EMS system showed that the number of resuscitation attempts had
      evident tendency to increase. The rates of return of spontaneous circulation and
      survival in patients with cardiac arrest of presumed cardiac origin increased
      from 32.5% to 58.6% (P < .05) and from 7.5% to 25.7% (P < .05) respectively.
      Thus, implementation in the EMS system of mobile intensive care, ACLS units, and
      standard resuscitation training program diminished mortality from sudden cardiac
      arrest.

PMID- 10919543
TI  - Heat stroke in a subtropical country.
AB  - In Taiwan, a subtropical country without any history of heat waves, heat stroke
      has been considered a rare disease. However, after seeing several cases of the
      classic type of heat stroke at the end of the summer of 1998 (an unusual event)
      we began to review and collect cases of suspected heat stroke (hyperthermia
      (>40.6 degrees C) in the presence of altered mental status and anhidrosis) and
      tried to explore the possible cause of this unusual phenomenon. Through a
      emergency department (ED) chart review, case retraction from International
      Classification of Diseases (ICD) code, and ED conferences, six patients were
      found for the period from June to August (the hottest months in Taiwan) 1998. We
      found that the most common comorbid conditions were hypertension (4/6) and
      preexisting mental problems (3/6). All patients lived in the inner part of an
      urban area, were middle class, and were not socially isolated. Most of our
      patients felt unhealthy being exposed to the cold and avoided staying in air
      conditioned rooms. Laboratory abnormalities and clinical presentations, except
      for a high fever and conscious change, seemed to be nonspecific. All cases
      occurred during two periods of sustained hotter-than-average weather and, to our
      surprise, we found that three episodes occurred around the day of the highest
      weather temperature (38.1 degrees C). However, the higher temperatures (around 30
      degrees to 31 degrees C and 32 degrees to 33 degrees C) did not reach the
      criteria of a heat wave. Compared with the other study, our patients seemed to
      have initial worse outcomes. Because of special environment and social factors,
      classic heat stroke may occur occasionally in subtropic regions, without previous
      history of heat waves and where heat stroke rarely occurs, during periods of the
      persistently high temperatures. Prevention of heat stroke in an area with a low
      incidence includes early health organizations' issue of advisories or warnings
      through the media and reminding or teaching emergency physicians about heat
      stroke during sustained hot weather, especially when record temperatures are set.

PMID- 10919544
TI  - Trauma: an annotated bibliography of the recent literature, 1999.

PMID- 10919545
TI  - Inhaled heliox does not benefit ED patients with moderate to severe asthma.

PMID- 10919546
TI  - Indwelling foley catheter causing extraperitoneal bladder perforation.

PMID- 10919547
TI  - Intravenous ketorolac in the treatment of fever.

PMID- 10919549
TI  - A simple technique to date the onset of anisocoria.

PMID- 10919548
TI  - Analgesic nitrous oxide: an opioid treatment for migraine.

PMID- 10919550
TI  - Acrometastasis.

PMID- 10919551
TI  - Unusual cause of acute respiratory distress: gonococcal endocarditis.

PMID- 10919552
TI  - Saxophone spermatic cord hematoma.

PMID- 10919553
TI  - Intra-abdominal injury from softball.

PMID- 10919554
TI  - Prehospital fibrinolytic therapy administered by a fire rescue engine crew.

PMID- 10919555
TI  - Hyperlactatemia and hyperammonemia as secondary effects of valproic acid
      poisoning.

PMID- 10919557
TI  - Emergency department follow-up of hospitalized patients.

PMID- 10919556
TI  - Successful resuscitation from cardiac arrest using mechanical CPR.

PMID- 10919558
TI  - Preventing adverse events and outcomes encountered using dermabond.

PMID- 10919559
TI  - Human intravenous immunoglobulin preparation and virus inactivation by
      pasteurization and solvent detergent treatment.
AB  - Human intravenous immunoglobulin (IVIG) solutions were prepared by two different
      methods and compared to each other. The crude immunoglobulin fraction obtained
      from Cohn-Oncley fractionation of plasma was further purified and subjected to
      virus inactivation, either by polyethylene glycol precipitation and
      pasteurization at 60 degrees C for 10 hours, or by ion exchange chromatography
      and solvent/detergent treatment. The final preparations, formulated in 5%
      immunoglobulin solutions were characterized by in vitro analyses of biochemical
      and biological properties and compared with the samples of other manufacturer's
      IVIG solution products. The critical properties evaluated in this study were
      purity, molecular intactness, and the biological functions such as Fc function
      and anticomplementary activity. Virus inactivation and removal by processing
      steps and by deliberate virucidal steps, as described above, were tested on
      various human pathogenic viruses, such as human immunodeficiency and experimental
      model viruses. The tested viruses were successfully inactivated and removed. We
      conclude that the intravenous immunoglobulins prepared by two different methods,
      as described above, provide an equivalent viral safety and quality.

PMID- 10919560
TI  - Isolation of fully active and stable corn coleoptile lectins.
AB  - It appears that the reason for the lack of information and data about corn
      coleoptile lectin is due to the instability of preparation with a rapid loss of
      hemagglutinating activity and abundant precipitate. In this paper, we assayed
      phosphate, borate, tris, and ascorbate-sucrose extraction buffers to compare
      lectin activity and protein yield. The ascorbate-sucrose buffer (AS-buffer)
      proved to be the best extracting solution. In a second step, cold acetone was
      employed to concentrate crude lectin. An increase of specific activity from the
      first to the third acetone precipitation was obtained. The protective effect on
      hemagglutinating activity of AS-buffer led us to test cysteine, metabisulfite,
      borohydride, and dithiothreitol (DTT) as reducing agents. The compounds were
      ineffective. Dissociating gel electrophoresis of the acetone-purified lectin
      disclosed a band pattern of components around 60 kD, a second band at 29 kD, and
      minor bands close to 15 KD. The procedure is useful for the preparation of
      stable, high activity corn coleoptile lectin. Further purification using affinity
      chromatography, as in reference (1) could become a major advance to obtain corn
      lectin of adequate purity for sequential analysis.

PMID- 10919561
TI  - Preparative binding of Coomassie brilliant blue to bovine serum.
AB  - Laboratory scale preparation of bovine serum albumin (BSA) stained with Coomassie
      brilliant blue (CBB) at alkaline pH is first described. Physical-chemical
      analyses of CBB-BSA showed that the unprotonated (anion) CBB dye binds tightly to
      BSA in buffered media of pH 8.2. Characteristic differences in spectra
      lambda(max) and molar absorptivities were found for the free anion CBB dye versus
      the CBB-BSA complex. Binding studies with low versus high dye/protein
      concentration ratios at alkaline pH gave values for n, binding site numbers, and
      K, intrinsic binding coefficient, consistent with those reported in analytical
      studies under acidic pH, but higher than values for neutral pH. Comparative
      analyses of Beer's law plots for the alkaline CBB-BSA complex under different
      experimental conditions showed its high stability toward various interferences,
      such as pH, strong detergents, temperature, light, prolonged storage, as well as
      high affinity for tannins. The hydrophobic nature of the CBB-BSA association at
      alkaline pH was tested.

PMID- 10919563
TI  - Studies on the synthesis of N(G)-nitro-L-arginine derivatives and their effects
      on septic shock.
AB  - (HCl x N(G)-NO2-Arg)2Lys-OCH3, (HCl x N(G)-NO2-Arg)2Lys-OH, [(HCl x N(G)-NO2
      Arg)2Lys]2Lys-OCH3, and [(HCl x N(G)-NO2-Arg)2Lys]2Lys-OH were synthesized by use
      of a solution method. Their effect on septic shock was studied in vivo. The
      results indicate that increasing the number of N(G)-NO2-Arg residues in a
      molecule may be useful to improve the response to septic shock.

PMID- 10919562
TI  - Synthesis and analgesic activity of N,N'-dicarbonyltryptamines.
AB  - 5-Methoxytryptamine and L-tryptophan methyl ester were acylated with malonic
      acid, dimethyl malonate, or succinic anhydride to produce the corresponding N,N'
      dicarbonyltryptamine derivatives. The analgesic activity was evaluated by the
      tail flick test. All of the compounds exhibited desirable analgesic potency. This
      result is consistent with that of N-(N-acetyl-L-tryptophanyl)-5-methoxytryptamine
      and confirmed that introducing substituted tryptamine into the amide chain of
      melatonin does enhance analgesic potency.

PMID- 10919564
TI  - Synthesis of RGD containing peptides and their vasodilation effect.
AB  - APLRV, SLRR, RGDS, and RGDF were synthesized by use of the solution method via
      the corresponding protective intermediates. After fragment condensation and
      deprotection, APLRVRGDS, APLRVRGDF, SLRRRGDS, and SLRRRGDF were obtained. The
      effect of these RGD containing peptides on rat aortic strips pretreated with
      noradrenaline (NE) were observed. The relaxing extents of contracted strips for
      them at three doses (10(-5) mol/L, 10(-6) mol/L and 10(-7) mol/L) indicated that,
      in a few cases, this kind of combination of these fragments may enhance the
      desirable activity.

PMID- 10919565
TI  - Maintenance immunosuppression after renal transplantation: identify those who
      need little or less.

PMID- 10919566
TI  - Immunosuppression in the post-adaptation period.

PMID- 10919567
TI  - Auxiliary liver transplantation with or without portal blood?

PMID- 10919568
TI  - Engineering of human vascular aortic tissue based on a xenogeneic starter matrix.
AB  - BACKGROUND: The goal for tissue engineering of vascular grafts is the replacement
      of a diseased vessel with a functional and stable graft. We now introduce a new
      concept for the tissue engineering of vessels. The idea was to humanize a
      previously acellularized, but structurally intact, xenogeneic vessel by
      repopulation with human autologous cells. To this purpose, a gentle nondenaturing
      and nondeterging acellularization procedure for xenogeneic aortas was developed.
      This structure was reseeded with pre-expanded peripheral vascular endothelial
      cells (EC) and myofibroblasts using specifically designed bioreactors. METHODS:
      Aortas from 15-30 kg female landrace pigs were acelullarized with a 0.1% trypsin
      solution for between 24 and 96 hr. Human vascular cells were harvested from
      saphenous vein biopsy specimens. Acellularized vessels were reseeded with EC and
      myofibroblasts. Cell viability after reseeding was assayed by fluorescence
      staining. Morphologic features of the acellularized matrix and tissue engineered
      vessel was assayed by transmission and scanning electron microscopy and
      histologic analysis. Nitric oxide-synthetase activity was investigated by mass
      spectrometric analysis of bioreactor supernatants. The in vivo immune response
      was tested by subcutaneous implantation of acellularized porcine aortic tissue in
      a rat model. RESULTS: The acellularization procedure resulted in an almost
      complete removal of the original resident cells, and the 3-D matrix was loosened
      at interfibrillar zones. However, the 3-D arrangement of the matrix fibers was
      grossly maintained. The 3-D matrix was covered with a fully confluent human
      endothelial cell layer obtained by continuous stress challenge in the bioreactor.
      Myofibroblasts migrated into positions formerly occupied by the xenogeneic cells.
      Nitric oxide synthetase activity was maintained in the bioartificial graft. T
      lymphocyte and CD18 positive leukocyte infiltrate were greatly reduced after
      acellularization of porcine aortic specimens after implantation in the rat.
      CONCLUSIONS: Porcine vessels were acellularized and consecutively fully
      repopulated with human EC and myofibroblasts. This approach may eventually lead
      to the engineering of vessels immunologically acceptable to the host using a
      relatively short preparation period of 2-3 weeks. We expect matrix turnover in
      vivo leading to a gradual assimilation of the matrix structure by the host
      mediated by the hosts autologous cells.

PMID- 10919569
TI  - Long-term survival of nonhuman primates receiving life-supporting transgenic
      porcine kidney xenografts.
AB  - BACKGROUND: Recently, there has been a resumed interest in clinical
      xenotransplantation using pig organs. However, no data are available yet
      regarding the capacity of porcine organs to sustain the life of a primate beyond
      the first month. We have attempted to obtain long-term survival of nonhuman
      primates using human decay-accelerating factor (hDAF) transgenic pig organs and
      an immunosuppressive strategy particularly aimed at neutralizing the humoral
      component of the immune response. METHODS: hDAF transgenic or control kidneys
      were transplanted into 14 bilaterally nephrectomized cynomolgus monkeys (Macaca
      fascicularis) that underwent splenectomy and were immunosuppressed with
      cyclosporine A, cyclophosphamide, and steroids. All animals also received
      recombinant erythropoietin. Postoperatively, the primates were monitored daily.
      Laboratory evaluations included serum biochemistry, hematology, and measurements
      of hemolytic antipig antibodies. To assess the role of splenectomy in the control
      of humoral response, historical data were also used from a group of monkeys (n=7)
      that received the same immunosuppressive regimen and an hDAF transgenic porcine
      kidney but did not have splenectomy or receive recombinant erythropoietin.
      RESULTS: This immunosuppressive approach obtained the longest survival time (78
      days) described to date of a primate receiving a life-supporting porcine renal
      xenograft. Furthermore, four of nine animals in this series survived for 50 days
      or more. Most biochemical measurements in this study (including plasma urea,
      creatinine, sodium, and potassium concentrations) remained within normal ranges
      for several weeks in all of the longest-surviving animals. CONCLUSIONS:
      Normalization of renal function (urea and creatinine) in primate recipients of
      porcine renal xenografts suggests that pig kidneys may be suitable for future
      clinical xenotransplantation. Additional immunosuppressive approaches,
      specifically designed to prevent humorally mediated immunological damage, should
      be explored to further prolong survival of primates that have received porcine
      xenografts.

PMID- 10919570
TI  - Comparison of University of Wisconsin and St Thomas' Hospital solutions on
      endothelium-derived hyperpolarizing factor-mediated function in coronary micro
      arteries.
AB  - BACKGROUND: It is controversial whether coronary endothelial function is impaired
      after cold exposure to University of Wisconsin (UW) or St. Thomas' Hospital (ST)
      solution during heart transplantation. We therefore examined the effects of cold
      storage of coronary micro-arteries with UW or ST solution on endothelium-derived
      hyperpolarizing factor (EDHF)-mediated function. METHODS: Porcine and human
      coronary arteries were immersed in either UW or ST solution at 4 degrees C for 4
      hr and then normalized in a wire myograph. RESULTS: In the rings (normalized
      diameter: 200-500 microM) precontracted by U46619, EDHF-mediated relaxation and
      hyperpolarization were initiated by bradykinin (BK) or A23187 in the presence of
      indomethacin and NG-nitro-L-arginine. In the human coronary arteries, the EDHF
      mediated relaxation to BK was reduced by UW solution from 53.2+/-5.6% to 24.0+/
      2.7% (P=0.006). The reduced EDHF-mediated relaxation occurred concurrently with
      the decreased hyperpolarization to BK (17.0+/-1.5 vs. 10.5+/-1.1 mV, n=10,
      P=0.004) or A23187 in porcine coronary arteries. In the control arteries, K+
      channel blockers, either glybenclamide or tetraethylammonium reduced the EDHF
      mediated relaxation. After exposure to UW solution, the EDHF-mediated relaxation
      was further significantly inhibited. In contrast, ST solution did not affect
      these responses. CONCLUSIONS: These results show that in coronary micro-arteries,
      UW, but not ST, solution impairs the EDHF-mediated function and inhibits the Ca2+
      activated and ATP-sensitive K+ channels. Our comparative study suggests that ST
      solution may be superior to UW solution in preserving the EDHF-related
      endothelial function of coronary micro-arteries.

PMID- 10919571
TI  - Importance of donor-derived lymphocytes in the protection of pancreaticoduodenal
      or islet grafts from recurrent autoimmunity: a role for RT6+NKR-P1+ T cells.
AB  - BACKGROUND: A rat pancreas transplantation model with insulin-dependent diabetes
      mellitus (IDDM) recurrence was established using a Wistar-Furth (WF; RT1u, RT6.2)
      rat as a donor and diabetes-prone (DP; RT1u, rt6.1 gene carrier) BioBreeding rat
      as a recipient. Interestingly, NKR-P1+TCRalphabeta+ (NKT) cells have recently
      been reported to have immunoregulatory functions in preventing autoimmune
      diabetes. The purpose of this study was to specifically examine the contribution
      of NKT cells in the prevention of IDDM recurrence. METHODS: Graft survivals with
      or without anti-intercellular adhesion molecule-1/leukocyte function-associated
      antigen-1 monoclonal antibodies were examined comparing pancreaticoduodenal (PD)
      transplantation with islet transplantation or pancreas-alone transplantation
      excluding duodenum and peripancreatic lymph nodes, in an IDDM recurrent model.
      The cells of the spleen were analyzed by flow cytometry (including intracellular
      interleukin (IL)-4 analysis), and serum cytokine levels (IL-4 and interferon
      gamma) were determined by enzyme-linked immunosorbent assays (ELISA). RESULTS:
      Only those DP recipients transplanted with PD grafts with monoclonal antibody
      treatment were free from IDDM. Flow cytometric analyses of spleen cells showed
      that NKT cells in them, compared with those in the recurrent DP recipients (mean
      <7%), increased significantly (13.7+/-3.1% in the total splenic T cells), most of
      which (85.9+/-4.3%) were derived from the donor (RT6.2+). The absolute number of
      RT6+NKT cells significantly increased in the nonrecurrent DP recipients, whereas
      that of RT6-NKT cells was similar with those of the other recurrent DP
      recipients. These RT6+NKT cells were predominantly CD4+ and showed significantly
      more expressions of intracellular IL-4 than the other T cells. By ELISA, serum
      interferon-gamma was not detectable (< 13 pg/ml) in any of the rats. However, IL
      4 was detected at 111.6+/-47.8 pg/ml only in the nonrecurrent DP recipients.
      CONCLUSIONS: Unlike islet or pancreas-alone transplants, NKT cells, especially
      RT6+NKT cells derived from PD grafts, may have an important immunoregulatory
      function of preventing IDDM recurrence, involving a Th2 deviation.

PMID- 10919572
TI  - Neutralization of tumor necrosis factor-alpha action delays but does not prevent
      lung injury induced by alloreactive T helper 1 cells.
AB  - BACKGROUND: Lung injury occurs frequently after allogeneic bone marrow
      transplantation in association with graft-versus-host disease, an immune response
      that involves both cellular and cytokine components. In a murine model, we
      recently showed that cloned alloreactive T helper (Th)1 cells can cause lung
      injury associated with increased production of tumor necrosis factor (TNF)-alpha
      by alveolar macrophages (J Immunol 1998; 161: 1913). METHODS: To evaluate the
      role of TNF-alpha in this model, we injected in vitro-activated Th1 cells into
      the following: (1) recipients deficient in receptors for TNF; (2) C57BL/6 control
      mice; (3) C57BL/6 mice, pretreated with soluble TNFRIIFc (a dimorphic high
      affinity TNF antagonist); (4) mice expressing TNFRIIFc transgene under control of
      the surfactant apoprotein C promoter (SPCTNFRIIFc); and (5) wild-type littermate
      controls (C57BL/6) (n=3-6 mice/group). RESULTS: At 1 and 3 days after i.v. Th1
      cell transfer, recipients were killed for analysis of lung histology,
      bronchoalveolar lavage (BAL) protein, and BAL cell counts. Control mice (wild
      type) at day 1 after injection had a mild to moderate mononuclear perivasculitis
      and increased interstitial cellularity. At day 3, lesions were more severe and
      perivasculitis also involved larger veins. TNFR-deficient mice had normal lung or
      minimal lung inflammation at day 1. At day 3, perivasculitis of medium-sized
      vessels was present, but there was no apparent involvement of larger veins.
      Results in mice treated with soluble TNFRIIFc and transgenic mice (SPCsTNFRIIFc)
      were similar to controls. BAL protein and BAL cell counts did not differ between
      any of the experimental groups. CONCLUSIONS: We conclude that lung inflammation
      induced by Th1 cells may be only delayed when TNF-alpha action is blocked. The
      persistence of abnormalities indicates that other proinflammatory pathways are
      involved in injury caused by these cells.

PMID- 10919573
TI  - Importance of portal flow diversion in experimental auxiliary partial orthotopic
      liver transplantation.
AB  - BACKGROUND: Auxiliary partial orthotopic liver transplantation (APOLT) has
      successfully been performed in patients with noncirrhotic metabolic diseases. It
      remains, however, unclear if intervention in the portal venous inflow is
      necessary to ensure adequate portal blood flow to graft and host liver. In this
      experimental study we evaluate the hepatic flow during APOLT. METHODS: Left
      lateral/medial segmental grafts were transplanted from beagle to dalmatian dogs.
      Vascular structures were anastomosed end-to-end. The effect of diversion of the
      portal flow was studied in three groups: in the ligation group (n=3) the host
      portal vein was tied off, the free flow group (n=6) had random flow to both
      livers. In the banding group (n=11) the host portal vein was banded with a
      adjustable strapband to restore the pretransplantation flow distribution.
      RESULTS: After reperfusion the blood flow through the common portal vein
      decreased from 49 to 36 ml/kg/min (P<0.03) in all animals. Flow through the left
      portal vein decreased from 26 to 5 ml/kg/min (P<0.0001). Banding restored the
      flow in the left portal vein to 12 ml/kg/min, although the flow in the free-flow
      group remained 4 ml/kg/min. In the ligation group the total portal flow was
      forced toward the graft leading to the highest perfusion: 24 ml/kg/min (P<0.005).
      Adverse effect of this ligation was the development of portal hypertension.
      CONCLUSIONS: This experimental study confirms that diversion of the portal flow
      is necessary for adequate graft perfusion in APOLT. Banding can restore the
      pretransplantation flow distribution, without compromising the flow in the common
      portal vein.

PMID- 10919574
TI  - Obliterative lesions in a heterotopic bronchial xenograft model--a preliminary
      study.
AB  - BACKGROUND: We further developed our heterotopic pig model of obliterative
      bronchiolitis to study airway obliteration in xenografts. METHODS: Four domestic
      piglets each received 40 bronchial xenografts s.c. from a donor lamb. Piglet X
      was not immunosuppressed. The other animals received daily oral cyclosporine, 15
      mg/kg (XC), or SDZ RAD, 1.5 mg/kg (XR), or both (XCR). Five implants at a time
      were serially removed from each animal during 17 days for histological
      assessment. RESULTS: In contrast to the grafts of the others, the xenografts of
      XCR recovered after initial ischemic damage. No epithelial damage (P<0.01) or
      mural necrosis occurred on day 7. Airway obliteration developed in all, but was
      significantly delayed in XCR. CONCLUSIONS: Invariably developing airway
      obliteration in nontreated xenografts was delayed by immunosuppression, making
      the model useful, especially in testing the efficacy of immunosuppressive drugs
      in a xenogeneic system.

PMID- 10919575
TI  - Permanent life support by kidneys perfused with a vitrifiable (7.5 molar)
      cryoprotectant solution.
AB  - BACKGROUND: Vitrification (glass formation) is a potential method for indefinite
      term organ preservation that eliminates all of the conventional problems of
      freezing and thawing. A 7.5 M mixture of cryoprotectants known as VS4 is
      sufficiently concentrated, in combination with applied pressure, to preclude ice
      formation entirely during cooling to below the glass transition temperature
      (about -125 degrees C), at which point vitrification takes place, arresting
      further changes over time. METHODS: Rabbit kidneys were perfused with VS4
      according to three different protocols. The kidneys were evaluated using an
      autograft model with immediate contralateral nephrectomy. RESULTS: All three
      methods permitted long-term survival, but the best results were obtained when the
      highest concentrations were perfused at about -3 degrees C. Using the latter
      protocol, the survival rate was 10/10, serum creatinine returned to a normal
      baseline after transient elevation, other clinical chemistry results normalized,
      and no histological damage was apparent 3 weeks after autografting. CONCLUSIONS:
      The results described provide the strongest evidence to date that it may be
      possible to bank kidneys for unlimited periods in the absence of ice for later
      transplantation.

PMID- 10919576
TI  - Transplanted cryopreserved encapsulated porcine hepatocytes are as effective as
      fresh hepatocytes in preventing death from acute liver failure in rats.
AB  - BACKGROUND: An implantable bioartificial liver (BAL) using xenogeneic isolated
      hepatocytes may be an alternative method to orthotopic liver transplantation for
      treatment of acute liver failure. The purpose of this study was to demonstrate
      that not only fresh but also cryopreserved porcine hepatocytes could be used in a
      BAL to prevent death after the onset of acute liver failure in rats. METHODS:
      Acute liver failure was induced by two-stage 95% hepatectomy. At the time of
      completion of liver resection, 100 rats were assigned to undergo or not undergo
      transplantation into the peritoneum of 4 meters of hollow fibers filled with 60
      million either fresh or cryopreserved porcine hepatocytes, or syngeneic
      hepatocytes, or culture medium, or of 60 million nonencapsulated cryopreserved
      porcine hepatocytes without immunosuppressive therapy. Survival rates at 7 days
      were compared between the different groups. RESULTS: In the control groups of
      hepatectomized animals not receiving encapsulated hepatocytes, 69-79% of the rats
      died from acute liver failure. The mortality rate was reduced to 15% (2 of 13) in
      rats receiving fresh porcine hepatocytes (P<0.01), 25% (4 of 16) in rats
      transplanted with either cryopreserved or syngeneic hepatocytes (P<0.05).
      Survival rates were maintained when hollow fibers were explanted > or =4 days
      after hepatectomy. In surviving rats, the weight of the remnant native liver
      increased with time and returned to the initial weight after 1 month.
      CONCLUSIONS: The implantable BAL using xenogeneic porcine hepatocytes was able in
      preventing death from acute liver failure without immunosuppressive therapy.
      Encapsulated cryopreserved hepatocytes were as effective as fresh hepatocytes.

PMID- 10919577
TI  - Arteriosclerosis in rat aortic allografts: early changes in endothelial integrity
      and smooth muscle phenotype.
AB  - BACKGROUND: Transplant arteriosclerosis remains a limiting factor for the long
      term survival of transplanted organs and effective treatment is lacking. A rat
      model of aortic allografts was used to analyze this process by electron
      microscopy and further characterize the phenotypic properties of the cells
      involved. METHODS: A segment of abdominal aorta was transplanted orthotopically
      from Fischer to Lewis rats. The animals were killed 1-12 weeks after the
      operation (four to six rats/group), and the grafts were removed and processed for
      microscopy. RESULTS: The first changes (1 week) included detachment of
      endothelial cells, adhesion of degranulating platelets to the subendothelial
      matrix, and modification of smooth muscle cells in the media. The latter process
      was distinguished by loss of myofilaments and formation of a prominent
      endoplasmic reticulum and Golgi complex (shift from contractile to synthetic
      phenotype). Subsequently, modified smooth muscle cells invaded the intima. In
      parallel, lymphocytes and monocytes/macrophages infiltrated the intima and
      adventitia. The neointima grew in size by cell proliferation and production of
      extracellular matrix (4-8 weeks). Smooth muscle cells and monocytes/macrophages
      in the neointima and media were also noted to accumulate cytoplasmic lipid
      droplets and eventually turn into foam cells and die. Within the lipid-rich cell
      remnants, calcification occurred. Finally (12 weeks), the growth in mass of the
      intimal lesions ceased and in some places reformation of an endothelial lining
      was detected. Few viable smooth muscle cells remained in the media and the
      inflammatory infiltrate in the adventitia was reduced. CONCLUSIONS: These
      observations highlight the importance of early changes in endothelial integrity
      and smooth muscle phenotype in the development of allograft vascular disease and
      form the basis for a partly modified model of the cellular mechanisms in this
      process.

PMID- 10919578
TI  - Auxiliary rat liver transplantation with portal vein arterialization in acute
      hepatic failure.
AB  - BACKGROUND: The aim of our work was to study the effect of the portal vein
      arterialization of an auxiliary liver graft on survival, liver function, and
      regeneration of the native liver suffering from surgically induced acute liver
      failure (ALF). METHODS: In Lewis rats (control group: n=10), ALF was induced by
      resection of about 85% of liver tissue. The auxiliary liver graft (reduced size
      of 30%) was transplanted into the right upper quadrant of the abdomen (trial
      group: n=12). The portal vein was arterialized via the renal artery. The
      infrahepatic vena cava was anastomosed end-to-side, and the bile duct was
      implanted into the duodenum. RESULTS: Survival rate over a 3-month period was
      10/12 in the trial group vs. 2/10 in the controls. In the trial group, the
      prothrombin time rose up to 38+/-2 sec on day 1 after surgery (control group:
      66+/-6 sec); on day 5 after surgery, it returned to values of 30+/-1 sec. On day
      1 after surgery, serum albumin fell to 25+/-1 g/L (preoperative value: 32+/-1
      g/L). Within 3 weeks, it returned to normal. The hepatobiliary scan on day 7
      after surgery showed normal uptake in the liver graft, whereas the uptake of the
      native liver was distinctly reduced. After 3 months, the transplanted liver had
      atrophied (0.6% of body weight), the native liver hypertrophied (2.5% of body
      weight), with a normal total weight for both livers of 3.1% of body weight.
      CONCLUSIONS: Thus, auxiliary liver transplantation with arterialized portal vein
      allows maintenance of liver function at the time of ALF and regeneration of the
      native liver.

PMID- 10919579
TI  - Long-term host unresponsiveness to encapsulated xenogeneic myoblasts after
      transient immunosuppression.
AB  - BACKGROUND: Encapsulating cells prevents the immune destruction of allogeneic
      cells in the subcutaneous site as well as allogeneic and xenogeneic cells in the
      central nervous system. However, when encapsulated xenogeneic cells are implanted
      s.c., they may be subject to rejection by the host. METHODS: Murine C2C12
      myoblasts engineered to secrete mouse erythropoietin (mEpo) were used to evaluate
      the response of control versus FK506-treated xenogeneic recipients (Fischer rats)
      to encapsulated myoblasts implanted in the s.c. site. RESULTS: Encapsulated C2C12
      mEpo cells were rapidly eliminated in immunocompetent Fischer rats. Devices
      transplanted into nude rats induced a sustained increase in the hematocrit,
      associated with an extended viability of the encapsulated cells. Short-term
      immunosuppression with FK506, for periods lasting either 1, 2, or 4 weeks after
      implantation, permitted the long-term survival of encapsulated C2C12 mEpo cells
      in Fischer rats. Animals increased their hematocrits to more than 70% and
      maintained these levels for 13 weeks, independent of the duration of FK506
      treatment. Unencapsulated C2C12 mEpo cells injected i.m. in immunosuppressed
      animals were rejected over this same period. CONCLUSIONS: Encapsulation alone
      cannot protect xenogeneic myoblasts from immune destruction in the s.c. site.
      These results highlight the importance of combining the technique of cell
      encapsulation with transient immunosuppression to achieve long-term survival of
      xenografted myoblasts in a peripheral immunoreactive site.

PMID- 10919580
TI  - Natural killer cell- and macrophage mediated discordant guinea pig-->rat
      xenograft rejection in the absence of complement, xenoantibody and T cell
      immunity.
AB  - BACKGROUND: The role of natural killer (NK) cells and macrophages (Mos) in the
      absence of T cell immunity in discordant xenograft (xg) rejection was
      investigated. METHODS: Guinea pig hearts were transplanted into athymic nude rats
      receiving no treatment or antixenoantibody (xAb), anticomplement (C), antinatural
      killer (NK) cell therapy (antiasialo GM1 [anti-ASGM1]) or their combinations. For
      anti-xAb therapy, natural xAbs were absorbed/neutralized by pretransplant guinea
      pig blood transfusion (pGPBT), followed by administration of the
      malononitriloamide MNA715. Cobra venom factor (CVF) was administered as anti-C
      therapy. FACScan analysis and a standard cytotoxicity assay determined NK cell
      number and cytotoxicity, respectively. ELISA and the CH50 assay measured titers
      of xAb and C activity, respectively. Rejected Xgs were examined by light
      microscopy and by immunohistochemistry. RESULTS: All hyperacutely (15+/-4 min)
      rejected Xgs from untreated rats showed deposits of C3 and IgM without cellular
      infiltrates. Combined anti-xAb and anti-C (pGPBT/MNA715/CVF) treatment
      significantly prolonged the survival of Xgs (3.7+/-0.6 days, P<0.001 vs. control
      group) showing NK cell and Mo infiltration without deposition of xAbs or C3. NK
      cell depletion (day -12) followed by exposure of recovering NK cells to the
      guinea pig antigens failed to induce specific NK cell nonresponsiveness and to
      further prolong xg survival in combined anti-xAb/anti-C group. In contrast,
      adding of continuous and repetitive depletion of NK cells significantly further
      prolonged xg survival to 7.4+/-0.5 days (P<0,001 vs. the anti-xAb/anti-C group)
      with rejected Xgs densely infiltrated by activated Mos without involvement of NK
      cells, C or xAbs. CONCLUSIONS: When xAb and C are suppressed in the discordant
      guinea pig-into-nude rat model, NK cells play an important role in xg rejection.
      When also NK cells are suppressed, activated Mos seem to reject discordant Xgs.
      The induction of specific NK cell nonresponsiveness fails in the guinea pig-into
      rat combination.

PMID- 10919582
TI  - Combined liver and kidney transplantation in children.
AB  - BACKGROUND: Preexisting renal dysfunction has been reported to significantly
      increase the morbidity and mortality associated with orthotopic liver
      transplantation (OLT). OLT alone has been recommended for adults and children
      with end-stage liver disease and reversible causes of renal failure (i.e.,
      hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT)
      has been shown to be an effective treatment for adults with combined end-stage
      liver and kidney disease. The purpose of this study was to examine the role of
      LKT in children. METHODS: Between October of 1984 and 1997, 385 children less
      than 18 years of age underwent OLT at the University of Chicago. During this same
      time period 12 patients underwent LKT. Data were gathered by retrospective review
      of the patients medical records and by interviews conducted with the patients'
      families. RESULTS: Actuarial patient survival was comparable for children who
      underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in
      the LKT group were the result of patient death and occurred within the first 90
      postoperative days. Factors associated with decreased patient survival included
      severity of illness as reflected by United Network of Organ Sharing status and
      LKT after failed OLT or cadaveric renal transplant. CONCLUSIONS: In children with
      concomitant endstage liver and kidney disease, LKT can be considered an effective
      therapeutic option in selected patients. Long-term patient survival in patients
      undergoing LKT is comparable to that of patients with normal renal function
      undergoing OLT alone.

PMID- 10919581
TI  - The effect of immunosuppression on posttransplant lymphoproliferative disease in
      pediatric liver transplant patients.
AB  - BACKGROUND: Posttransplant lymphoproliferative disease (PTLD) is a serious
      complication associated with the use of chronic immunosuppression for solid organ
      transplantation. This study represents a retrospective analysis of UCLA's
      experience with PTLD in all pediatric liver transplant recipients between 1984
      1997. We assessed the clinical presentation, risk factors, incidence density,
      immunological characteristics, management, and outcome of patients who developed
      PTLD when receiving either primary cyclosporin A (CsA) or tacrolimus. METHODS: A
      total of 251 children received primary CsA therapy of which 70 required OKT3 for
      steroid resistant rejection and 29 required tacrolimus rescue for OKT3 resistance
      and/or chronic rejection. One hundred forty one children received tacrolimus as
      primary therapy. Sixty patients who survived for less than 6 months after
      transplantation were excluded from the study. RESULTS: The total incidence
      density (ID) rate of PTLD was 1.8+/-0.4 per 100 patient-years (30/392). The
      overall ID rate of PTLD in the CsA group was 0.93+/-0.2 per 100 patient-years
      (15/251). Within this group of primary CsA-treated patients, the ID rate of PTLD
      was 0.49+/-0.1 without OKT3 or tacrolimus, 0.67+/-0.2 with OKT3, and 6.42+/-1.1
      with tacrolimus rescue. The overall PTLD ID rate in the primary tacrolimus
      treated patients was 4.86+/-1.2 per 100 person-years (15/141). There was a 5-fold
      increase in the ID rate of PTLD in the primary tacrolimus group when compared to
      the comparable, primary CsA group (P<0.001). The mean time to PTLD was 5-fold
      longer (49.7+/-20.7 months) in the CsA group when compared to the CsA/tacrolimus
      rescue group (9.8+/-3 months, P<0.05) or the tacrolimus primary group (12.6+/-5.1
      months, P<0.05). Five patients had monoclonal disease in the CsA group, but only
      one in the tacrolimus group (P<0.05). Clinical presentations with enlarged lymph
      nodes, fevers, malaise, anorexia, weight loss, hypoalbuminemia, and
      gastrointestinal blood loss were common. Mortality was 20%, three patients died
      in each group. CONCLUSION: The use of primary tacrolimus therapy was associated
      with a significant 5-fold higher rate of PTLD when compared to those treated with
      primary cyclosporine. Early diagnosis, decrease and/or discontinuation of potent
      immunosuppressive agents may contribute to decrease morbidity and mortality of
      this entity.

PMID- 10919584
TI  - Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ
      transplant recipients: a multicenter retrospective study. Italian Study Group of
      Fungal Infections in Thoracic Organ Transplant Recipients.
AB  - BACKGROUND: Fungal infections (FI) after solid organ transplantation (Tx) remain
      a major cause of morbidity and mortality. Aspergillus and Candida account for
      more than 80% of FI. METHODS: One thousand nine hundred and sixty-three patients
      undergoing thoracic organ Tx [1,852 heart and 111 lung (35 heart-lung Tx, 30
      double-lung Tx, 46 single-lung Tx)] in 12 Italian Centers between November 1985
      and January 1997 were included in the study. RESULTS: Fifty-one patients (41
      heart Tx - 2.2%; 9 heart-lung Tx - 25.7%; 1 single-lung Tx - 2.2%) developed 53
      invasive FI at a median of 58 days (range 6-2479) after Tx. Aspergillosis was the
      most frequent FI in our series accounting for 64.1% (34/53) of all FI [A
      fumigatus, n=29 (85.3%); A nidulans, n=2 (5.9%); A niger, n=2 (5.9%); A terreus,
      n=1 (2.9%)]; 30 (88.2%) patients developed invasive lung aspergillosis, 2 (5.9%)
      a tracheobronchitis, 1 (2.9%) a skin infection, and 1 (2.9%) a sternal wound
      infection. Twelve patients (22.6%) developed candidiasis [C albicans, n=8
      (66.6%); C krusei, n=1 (8.3%); C glabrata, n=1 (8.3%); C parapsilosis, n=1
      (8.3%); C sake, n=1 (8.3%)]. There were seven episodes (58.3%) of candidemia, two
      (16.7%) esophagitis, two (16.7%) gastritis, and one (8.3%) tracheobronchitis.
      Mortality was 29.4% for patients developing aspergillosis and 33.3% for those
      experiencing candidiasis. Furthermore, four patients developed the following: one
      C neoformans meningitis, one Sporothrix cyanescens pneumonia, one Rhizopus spp.
      tracheobronchitis, and one Trichosporon beigelii disseminated infection. Three
      additional patients were diagnosed affected by deep mould infection by histology
      alone. CONCLUSIONS: Deep-seated FI were relatively rare in our series, although
      their mortality rate is still very high.

PMID- 10919583
TI  - Randomized, prospective trial of mycophenolate mofetil versus azathioprine for
      prevention of acute renal allograft rejection after simultaneous kidney-pancreas
      transplantation.
AB  - BACKGROUND: In simultaneous kidney-pancreas (SPK) transplantation, manifestations
      of renal allograft rejection typically become evident before those of pancreatic
      rejection. This study compared mycophenolate mofetil (MMF) and azathioprine (AZA)
      in prevention of renal rejection after primary SPK transplantation. METHODS: In
      an open-label, randomized, multicenter study, patients received MMF 1.5 g twice
      daily (n=74) or AZA 1-3 mg/kg daily (n=76) for 1 year after transplantation. The
      incidence of rejection was assessed at 6 months. Adverse events were tracked
      through 1 year. Survival data are reported through 2 years. RESULTS: At 6 months,
      efficacy results for MMF vs. AZA patients, respectively, were the following:
      rejection (27% vs. 39%); rejection or death (34% vs. 42%); rejection, graft loss,
      death, or premature withdrawal (i.e., treatment failure; 41% vs. 55%). Six-month
      efficacy trends favored MMF, and time to rejection or treatment failure was
      significantly longer when compared with AZA (P=0.049). One-year efficacy results
      for MMF vs. AZA patients, respectively, were the following: treatment of renal
      rejection (35% vs. 47%); renal allograft loss or death (9% vs. 12%); pancreas
      allograft loss or death (15% vs. 14%). Five MMF patients (7%) and four (5%) in
      the AZA group died. More MMF than AZA patients developed opportunistic infections
      (54% vs. 38%), but the pathogens did not differ. CONCLUSIONS: Trends for most
      efficacy parameters favored MMF over AZA, and time to renal allograft rejection
      or treatment failure was statistically significantly longer for MMF. The use of
      MMF in the treatment of SPK recipients is a useful advance.

PMID- 10919585
TI  - CMV viral load measurements in whole blood and plasma--which is best following
      renal transplantation?
AB  - BACKGROUND: Quantitative commercial assays for cytomegalovirus (CMV) detection
      have recently been developed. Their role in the management of patients after
      transplantation needs to be evaluated. Widespread use of these assays will allow
      for comparison of results between centers and meaningful interpretation of the
      significance of viral load measurements. METHODS: Sequential samples from 52
      patients after renal transplantation were tested in the murex hybrid capture
      assay (HCA) and the Roche Amplicor CMV DNA assay (QPCR) and correlated with the
      development of CMV disease. A comparison of viral loads in plasma and whole blood
      was also made. RESULTS: Both assays were sensitive and detected all cases of CMV
      disease. The specificity and positive predictive value increased from 0.34 and
      0.36 to 0.85 and 0.96 for the HCA and 0.37, 0.37 to 0.72 and 0.63 for the QPCR
      following a receiver operator curve analysis. Higher viral loads were measured
      using the HCA compared to the QPCR. Response to ganciclovir was associated with a
      greater than 80% reduction in viral load by HCA or greater than 70% using the
      QPCR. CONCLUSIONS: Both assays were highly sensitive. By using a receiver
      operator curve analysis a cutoff viral load can be determined which maximizes the
      clinical utility of these assays.

PMID- 10919586
TI  - Cyclosporin drug-interaction-induced rhabdomyolysis. A report of two cases in
      lung transplant recipients.
AB  - In rare cases the use of cyclosporin in transplant patients can cause myopathic
      changes. We describe two patients, the recipients of lung transplants, who
      developed severe reversible rhabdomyolysis associated with cyclosporin drug-drug
      interaction.

PMID- 10919587
TI  - Addition of isradipine (Lomir) results in a better renal function after kidney
      transplantation: a double-blind, randomized, placebo-controlled, multi-center
      study.
AB  - BACKGROUND: After successful kidney transplantation patients may suffer from the
      adverse effects due to the use of calcineurin inhibitors. Calcium channel
      blockers are effective in the treatment of hypertension and may ameliorate
      cyclosporine- (CsA) induced impairment of renal function after kidney
      transplantation. Calcium channel blockers may also modulate the immune-system
      which may result in reduction of acute rejection episodes. PATIENTS AND METHODS:
      From June 1995 till 1997 the effect of isradipine (Lomir) on renal function,
      incidence and severity of delayed graft function (DGF), and acute rejection after
      kidney transplantation, was studied in 210 renal transplant recipients, who were
      randomized to receive isradipine (n=98) or placebo (n=112) after renal
      transplantation in a double-blind fashion. RESULTS: In the isradipine group renal
      function was significantly better at 3 and 12 months (P=0.002 and P=0.021)
      compared with the placebo group. DGF was present in both groups: isradipine:
      (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was
      comparable in both groups (isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No
      statistical difference was found in incidence or severity of biopsy-proven acute
      rejection [isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00].
      Renal vein thrombosis was observed in eight patients. This proved to be
      associated with the route of administration of the study medication [6/45 (13%)
      on i.v. medication versus 2/165 (1%) on oral medication, P<0.001]. CONCLUSIONS:
      Addition of isradipine results in a better renal function after kidney
      transplantation, without effect on incidence or severity of DGF or acute
      rejection.

PMID- 10919588
TI  - Successful surgical salvage of pancreas allografts after complete venous
      thrombosis.
AB  - BACKGROUND: Complete venous thrombosis of the pancreas after simultaneous
      pancreas-kidney (SPK) transplantation usually results in graft loss. We describe
      a technique that allows salvage of the graft after complete venous thrombosis.
      METHODS: A total of 150 patients with insulin dependent diabetes mellitus/end
      stage renal disease underwent SPK over the past decade at the University of
      Miami. Of these, three patients developed complete venous thrombosis after
      induction therapy with antiinterleukin-2R antibody and i.v. tacrolimus. These
      three patients underwent surgical thrombectomy followed by heparinization and
      oral anticoagulation. The splenic vein was opened distally at the tail of the
      pancreas and the superior mesenteric vein at the level of the mesentery or head
      of the pancreas. Thrombectomy was performed with a Fogarty catheter. The portal
      anastomosis was not opened or manipulated. The arterial "Y" graft was not clamped
      and the right iliac vein was controlled proximally with a double wrapped vessel
      loop to contain possible thrombus. In one patient, the partially thrombosed
      splenic artery was opened at the tail of the pancreas and thrombectomy was
      performed in the same fashion. There were no apparent technical problems. A
      pancreatic biopsy was not performed, nor was acute rejection treated empirically.
      RESULTS: Intraoperative and serial Doppler ultrasound showed good flow through
      the allograft. In all three patients the exocrine and endocrine function of the
      pancreas was preserved with a mean follow-up of 15 months. CONCLUSIONS: The
      described surgical thrombectomy followed by systemic anticoagulation may be
      useful in the salvage of the allograft pancreas in case of complete venous
      thrombosis.

PMID- 10919589
TI  - Early diagnosis of brain death in patients treated with central nervous system
      depressant drugs.
AB  - BACKGROUND: Among the main causes for the relatively small number of organ
      donors, the delay in the diagnosis of brain death plays a major role.
      Administration of drugs causing central nervous system (CNS) depression prevents
      diagnosis of brain death by clinical and electroencephalographic criteria until
      serum clearance of the drug has occurred. Confirming brain death by demonstrating
      persistent intracranial circulatory arrest might decrease the length of the
      diagnostic process. We have carried out a prospective study to investigate
      whether 99 mTc-hexamethyl propylenamino oxime (99mTc-HMPAO) brain scintigraphy
      and/or transcranial Doppler ultrasound can speed up the diagnosis of brain death
      in patients treated with CNS depressant drugs. METHODS: All 138 consecutive
      patients with severe brain lesion that progressed to brain death in our center
      between January 1994 and December 1996 were controlled. Of them, 36 patients aged
      1 to 65 years old (mean=25.6+/-18.3 years) who met clinical and EEG criteria for
      the diagnosis of brain death, except for the presence of significant serum levels
      of barbiturates (n=34), opiates (n=8), and benzodiazepines (n=3) were distributed
      in three groups according to the confirmatory test used; group 1: waiting for the
      metabolic clearance of CNS depressant drugs, or by demonstrating intracranial
      circulatory arrest with 99mTc-HMPAO (group 2) or transcranial Doppler (group 3).
      The delay in diagnosing brain death by the three methods was analyzed. RESULTS:
      The mean interval between the presumptive and the definitive diagnosis of brain
      death was 34.4+/-32.2 hr in group 1, 17.7+/-18.3 hr in group 2, and 5.0+/-4.6 hr
      in group 3 (P=0.004). The between-groups analysis showed that 99mTc-HMPAO and
      transcranial Doppler decreased the delay in diagnosing brain death with respect
      to waiting for drug clearance by 49% (P=0.16) and 85% (P<0.001), respectively.
      Moreover, transcranial Doppler decreased this time by 72% with respect to 99mTc
      HMPAO (P<0.01). CONCLUSIONS: Transcranial Doppler ultrasound and 99mTc-HMPAO
      brain scintigraphy can significantly reduce the time taken to confirm brain death
      in patients with significant serum levels of CNS depressant drugs. In this
      setting, transcranial Doppler is superior to 99mTc-HMPAO in reducing the waiting
      time for a firm diagnosis of brain death.

PMID- 10919590
TI  - Donor-specific T-cell reactivity identifies kidney transplant patients in whom
      immunosuppressive therapy can be safely reduced.
AB  - BACKGROUND: To reduce the side effects of long-term immunosuppressive therapy,
      stable renal transplant patients were routinely converted from cyclosporine to
      either azathioprine or mycophenolate mofetil. Thereafter, the azathioprine and
      mycophenolate mofetil dose was reduced to 75% at 4 months and to 50% at 8 months
      after conversion. We questioned whether the T-cell reactivity before conversion
      was able to predict which patients could be safely converted and tapered in their
      immunosuppressive load, while remaining free from acute rejection. METHODS:
      Before conversion, the T-cell reactivity of peripheral blood mononuclear cells
      against donor and third-party spleen cells were tested in mixed lymphocyte
      cultures. We measured the frequency of donor and third-party reactive helper T
      lymphocyte (HTLpf) and cytotoxic T-lymphocyte (CTLpf) precursors and their
      avidity for HLA class I antigens using limiting dilution analysis. Peripheral
      blood mononuclear cells were also stimulated with tetanus toxoid to test the
      general immune response. RESULTS: The tetanus toxoid response, reactivity to
      donor and third-party cells as measured in mixed lymphocyte cultures and HTLpf,
      and the avidity of cytotoxic T-lymphocyte precursors were not predictive for the
      development of acute rejection. However, significant differences were found in
      donor-specific CTLpf before conversion, between patients with and without acute
      rejection after conversion in immunosuppression. The donor-specific CTLpf was
      significantly lower in patients without compared to those with acute rejection
      (P=0.01). Additionally, when no CTLpf was detectable before conversion, acute
      rejection did not occur after conversion. Acute rejection was only diagnosed in
      patients with detectable CTLpf before conversion. CONCLUSION: The number of donor
      specific cytotoxic T-lymphocytes identifies patients in whom the
      immunosuppressive load can be safely reduced.

PMID- 10919591
TI  - Randomized study on the conversion of treatment with cyclosporine to azathioprine
      or mycophenolate mofetil followed by dose reduction.
AB  - BACKGROUND: The introduction of cyclosporine (CsA) in kidney transplantation has
      improved early graft survival. However, its long-term use is associated with
      impairment of renal function and increased cardiovascular risk factors. To avoid
      CsA-related long-term adverse effects, patients were converted to either
      azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation.
      METHODS: Between September 1995 and January 1997, 64 stable renal transplant
      recipients on CsA and prednisone treatment were included in a prospective,
      randomized study. Patients were randomized for conversion of CsA to 2 mg/kg AZA
      (n=30) or 1 g of MMF twice daily (n=34). All patients remained on low-dose
      steroids. To decrease the total immunosuppressive load, a dose reduction in MMF
      and AZA was performed at 4 and again at 8 months after conversion. Mycophenolic
      acid trough levels were measured at regular intervals. RESULTS: After conversion,
      a decrease in serum creatinine was found for both groups: for MMF, 132 to 109
      micromol/L (P=0.016); and for AZA, 123 to 112 micromol/L (P<0.0001). After
      conversion, more acute rejections occurred in the AZA group (11/30) compared to
      the MMF group (4/34) (P=0.04). Dose reduction of MMF to 500 mg twice daily and of
      AZA to 1.0 mg/kg elicited three rejections in both groups. The incidence of side
      effects and infections were similar. CONCLUSION: Discontinuation of CsA spared
      renal function. In patients converted to MMF significantly less rejections
      occurred compared to patients converted to AZA. Furthermore, dose reduction of
      both AZA and MMF is possible in the majority (72%) of the patients.

PMID- 10919592
TI  - Novel surveillance and cure of a donor-transmitted lymphoma in a renal allograft
      recipient.
AB  - BACKGROUND: In this report we describe a malignant lymphoma of donor origin
      inadvertently transplanted into two renal allograft recipients, despite standard
      comprehensive donor screening. The successful clearance of the tumor from both
      patients and a novel method of surveillance are detailed. METHODS: Initial
      management consisted of withdrawal of immunosuppression to promote rejection of
      the allograft and the transplanted tumor in both patients, followed by graft
      removal. Peripheral blood microchimerism was assessed in both recipients using
      nested polymerase chain reaction to detect the DYZ3 gene on the Y chromosome
      (donor male, recipients female). RESULTS: Although microchimerism was detected on
      day 6 after transplantation and day 1 after explantation, repeat peripheral blood
      examination at 1, 3, and 6 months after explantation demonstrated no
      microchimerism. Both patients remain well at 12 months and have been relisted for
      transplantation. CONCLUSION: Despite inadvertent transplantation of a previously
      undiagnosed malignancy of donor origin, the recipients' immune response was able
      to eliminate donor tumor cells after the withdrawal of immunosuppression.
      Repeated surveillance of peripheral blood from both recipients, using a novel
      application of the technique of nested polymerase chain reaction to amplify donor
      DNA, demonstrated no persistence of donor cells, supporting effective eradication
      of the donor malignancy.

PMID- 10919594
TI  - Cross-reactive group matching does not lead to a better allocation and survival
      of donor kidneys.
AB  - BACKGROUND: In cadaveric renal transplantation HLA-A, -B, -DR matching of donor
      and recipient is beneficial for graft survival. However, allocation based on HLA
      matching seems to favor recipients with more frequently occurring HLA antigens.
      In this study we investigated whether matching on the basis of cross-reactive
      groups (CREGs), defined according to the United Network for Organ Sharing (UNOS),
      would be a good alternative for the allocation of kidneys without negatively
      influencing graft survival. Theoretically, this approach would provide more
      recipients with an immunologically well-matched donor organ. METHODS: The
      influence of CREG matching on graft survival was studied in univariate analyses
      using the Eurotransplant database. RESULTS: No beneficial effect of CREG matching
      was observed, whereas a significant HLA matching effect was observed in the 0
      CREG mismatched donor/ recipient combinations. Only in the small subgroup with 1
      MM for HLA-A, -B and 0 MM for HLA-DR, a significantly better survival was
      observed, when this mismatch belonged to the 0 or 1 MM CREG group versus two or
      more MM CREG group. However, this subgroup concerns only 8% of the transplants
      performed. CONCLUSIONS: In contrast to other reports, our study showed that HLA
      matching is by far more beneficial than CREG matching. In the homogenous
      Eurotransplant population, adjusting the matching criteria toward CREG matching
      would not lead to an improved graft survival.

PMID- 10919593
TI  - Living donor liver transplantation for fulminant hepatic failure.
AB  - BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated
      only for elective cases of pediatric patients with end-stage liver disease. In
      Japan, however, where liver transplantation from brain-dead donor is performed
      very rarely, this indication has been expanded to emergency cases such as
      fulminant hepatic failure (FHF). METHODS: Thirty-eight patients with FHF were
      treated between May 1992 and April 1999. Causes of acute liver failure were non
      A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A
      virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one
      each. RESULTS: Four patients did not undergo LDLT because of severe brain damage
      or combined multiple organ failure. The remaining 34 patients underwent a total
      of 36 LDLTs, including two retransplantations; 16 children received transplants
      of 17 lateral segments, three children and eight adults transplants of 11 left
      lobes, and seven adults transplants of eight right lobes. A total of 15
      recipients died, four of primary graft dysfunction, three of refractory acute
      rejection, two of pneumonia, and one each of ductopenic rejection, sepsis,
      aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ
      failure by chrome poisoning, and unknown hepatic failure. Primary graft
      dysfunction developed in adult recipients with small-for-size graft transplants,
      whereas refractory acute rejection and ductopenic rejection occurred in six
      grafts each of children with non-A, non-B FHF. CONCLUSIONS: LDLT can be safely
      expanded to cases of FHF in adult patients. Primary graft dysfunction in adult
      recipients with small-for-size left lobe grafts can be overcome by using right
      lobes. However, refractory acute rejection and ductopenic rejection in children
      remain a major problem.

PMID- 10919595
TI  - Costimulatory molecules are active in the human xenoreactive T-cell response but
      not in natural killer-mediated cytotoxicity.
AB  - BACKGROUND: T-cell costimulatory blocking agents inhibit allospecific T-cell
      responses in vitro and prevent allograft rejection in vivo. Costimulatory
      requirements for discordant xenospecific cellular responses remain undefined. We
      have evaluated costimulatory molecule expression by porcine endothelial cells
      (PEC) after interaction with human cells and tested agents known to inhibit
      allospecific responses for their ability to inhibit xenospecific responses in
      vitro. METHODS: Human-specific agents were screened for their ability to bind
      porcine costimulatory molecules by FACS. Up-regulation of B7 molecules on PEC was
      evaluated by FACS after exposure to human cells or supernatants. The effect of
      human and/or porcine costimulatory blockade was tested in xeno-mixed lymphocyte
      reactions (XMLRs) and in natural killer (NK) cell cytotoxicity assays. RESULTS:
      B7 expression was induced on PEC after exposure to human T and NK cells or T cell
      conditioned medium. The human XMLR was attenuated by human CTLA4-Ig and anti
      human CD154 (hu5C8), and the combination was synergistic. Anti-human CD80 and
      CD86 antibodies alone had minor effects in the XMLR, but in combination with
      hu5C8 were as effective as human CTLA4-Ig plus hu5C8. Anti-hCD80 and hCD86
      antibodies that did not cross-react with porcine CD80 or CD86 were as effective
      in blocking the MLR as those that did cross-react, indicating that the
      predominant costimulation in vitro was derived from the responding cells. None of
      the agents affected the xeno-NK response. CONCLUSIONS: We conclude that the
      costimulation-modulating agents block human anti-porcine T-cell responses in
      vitro predominantly through interruption of costimulation derived from responding
      cells. They have no effect on NK cell-mediated cytotoxicity.

PMID- 10919596
TI  - Prolonged allograft survival in anti-CD4 antibody transgenic mice: lack of
      residual helper T cells compared with other CD4-deficient mice.
AB  - BACKGROUND: Investigations of the role of CD4 T lymphocytes in allograft
      rejection and tolerance have relied on the use of mouse models with a deficiency
      in CD4 cells. However, in mice treated with depleting monoclonal antibody (mAb)
      and in MHC class II knockout (KO) mice, there are residual populations of CD4
      cells. CD4 KO mice had increased CD4- CD8-TCRalphabeta+ helper T cells, and both
      strains of KO mice could reject skin allografts at the normal rate. In this
      study, transgenic mice with no peripheral CD4 cells were the recipients of skin
      and heart allografts. Results were compared with allograft survival in CD4 and
      MHC class II KO mice. METHODS: GK5 (C57BL/6 bml mice transgenic for a chimeric
      anti-CD4 antibody) had no peripheral CD4 cells. These mice, and CD4 and class II
      KO mice, received BALB/c or CBA skin or cardiac allografts. Some GK5 mice were
      treated with anti-CD8 mAb to investigate the role of CD8 cells in rejection. CD4
      and CD8 cells were assessed by FACS and immunohistochemistry. RESULTS: BALB/c
      skin on GK5 mice had a mean survival time +/- SD of 24+/-6 days, compared with
      9+/-2 days in wild-type mice. Anti-CD8 mAb prolonged this to 66+/-7 days. BALB/c
      skin survived 10+/-2 days on class II KO and 14+/-2 days on CD4 KO, both
      significantly less than the survival seen on GK5 recipients (P<0.001). BALB/c
      hearts survived >100 days in GK5 recipients and in wild-type recipients treated
      with anti-CD4 mAb at the time of grafting, in contrast to a mean survival time of
      10+/-2 days in untreated wild-type mice. Immunohistochemistry revealed that long
      term surviving heart allografts from the GK5 recipients had CD8 but no CD4
      cellular infiltrate. These hearts showed evidence of transplant vasculopathy.
      CONCLUSIONS: The GK5 mice, with a complete absence of peripheral CD4 cells,
      provide the cleanest available model for investigating the role of CD4
      lymphocytes in allograft rejection. Prolonged skin allograft survival in these
      mice compared with CD4 and MHC class II KO recipients was clearly the result of
      improved CD4 depletion. Nevertheless, skin allograft rejection, heart allograft
      infiltration, and vascular disease, mediated by CD8 cells, developed in the
      absence of peripheral CD4 T cells.

PMID- 10919597
TI  - Analysis of expression and function of the costimulatory molecule 4-1BB in
      alloimmune responses.
AB  - BACKGROUND: 4-1BB (CD137) is a T cell costimulatory molecule that promotes T cell
      activation. In this study, we investigated the role of 4-1BB costimulation in
      allogeneic T cell responses. METHODS: Vascularized heart transplantation,
      allogeneic mixed leukocyte reaction (MLR), and graft versus host disease models
      were used to examine 4-1BB and 4-1BBL expression. In addition, agonistic anti-4
      1BB antibodies were used in MLR to functionally analyze T cell responses.
      RESULTS: Using a heart transplant model, we found that 4-1BB and 4-1BBL
      transcripts were both expressed in rejecting cardiac grafts. In the allogeneic
      MLR, 4-1BB was expressed on both activated CD4 and CD8 T cells and 4-1BB was
      expressed on T cells after multiple cell divisions in vivo. Functionally, 4-1BB
      was a potent stimulator of proliferation, cytokine secretion, and CD25 expression
      by CD8 T cells, but 4-1BB signals had a weak effect on the proliferation of CD4 T
      cells. Because 4-1BB promoted the secretion of IL-2 and the expression of CD25 on
      CD8 T cells, we investigated whether IL-2 was the only factor whereby 4-1BB
      signals induced CD8 T cell proliferation. Although IL-2 was required for optimal
      CD8 T cell proliferation, 4-1BB also costimulated CD8 T cell proliferation
      independently of IL-2. CONCLUSIONS: This study demonstrates that 4-1BB is
      expressed on activated, maximally divided T cells and shows that 4-1BB promotes
      CD8 T cell proliferation by enhancing signals through the IL-2 receptor and by
      other mechanisms independent of the IL-2 pathway.

PMID- 10919598
TI  - Fas ligand-deficient gld mice are more susceptible to graft-versus-host-disease.
AB  - BACKGROUND: The Fas/Fas ligand (FasL) pathway plays an important role in a number
      of apoptotic processes that could be important for the development of graft
      versus-host disease (GVHD) after bone marrow transplantation (BMT), such as
      cytolysis of target cells by cytotoxic T cells, regulation of inflammatory
      responses, peripheral deletion of autoimmune cells, costimulation of T cells, and
      activation-induced cell death. METHODS: To study the role of the Fas/FasL pathway
      in the complex pathophysiology of graft versus host disease (GVHD), we used FasL
      deficient B6.gld mice as recipients in a Major Histocompatibility Antigen Complex
      matched minor Histocompatibility Antigen-mismatched murine model for GVHD after
      allogeneic BMT (C3H.SW-->B6). RESULTS: We found a significantly higher morbidity
      and mortality from GVHD compared to control B6 recipients. Histopathological
      analysis of the GVHD target organs demonstrated that B6.gld recipients developed
      significantly more thymic and intestinal GVHD. B6gld recipients with GVHD
      demonstrated an increased expansion of donor T cells and monocytes/ macrophages
      compared to control B6 recipients, whereas serum TNF-alpha levels were equivalent
      in B6.gld recipients and control B6 recipients. CONCLUSION: This study
      demonstrates that the expression of FasL in the BMT recipient is important for
      the host's ability to control GVHD.

PMID- 10919599
TI  - Immune response after adenoviral gene transfer in syngeneic heart transplants:
      effects of anti-CD4 monoclonal antibody therapy.
AB  - BACKGROUND: E1-deleted adenoviral vectors are frequently used for in vivo gene
      therapy. However, gene expression after adenovirus-(ad) mediated gene transfer is
      known to be transient due to the generation of an immune response against virus
      infected cells. In this study, we asked whether an anti-CD4 mAb (RIB 5/2)
      treatment may improve the gene transfer into rat cardiac grafts. METHODS: We
      injected recombinant ad-constructs encoding for Escherichia coli beta-gal into
      syngeneic rat heart transplants via the proximal aorta. One-half of the
      recipients of genetically modified grafts received the anti-CD4 mAb RIB 5/2,
      whereas the other half received no monoclonal antibody treatment. Genetically
      unmodified isografts without any treatment of the recipients were used as
      additional controls. At different time points hearts were harvested and analyzed
      for reporter gene expression, intragraft cellular infiltration, and cytokine gene
      expression (quantitative "real time" reverse transcriptase polymerase chain
      reaction). Serum samples were analyzed for anti-ad-Ig using enzyme-linked
      immunosorbent-assay. RESULTS: In control animals the beta-gal reporter gene
      expression slowly increased until day 7 and then declined. The immunohistological
      and reverse transcriptase polymerase chain reaction intragraft analyses revealed
      a strong inflammatory response (cellular infiltration, cytokine expression) in ad
      transfected grafts that may explain the delayed expression and fast down
      regulation of the transgene. Treatment with RIB 5/2 mAb resulted in a faster and
      prolonged reporter gene expression, reduced graft infiltration, reduced anti-ad
      Ig titers and less interferon-gamma up-regulation. CONCLUSIONS: Our results
      indicate that modulation of the anti-ad immune response using a nondepleting anti
      CD4 mAb may increase the efficiency of ad-vectors for gene therapy in the
      transplant setting.

PMID- 10919600
TI  - Conversion from tacrolimus to cyclosporin in stable renal transplant patients:
      safety, metabolic changes, and pharmacokinetic comparison.
AB  - BACKGROUND: Conversion from tacrolimus to cyclosporin has not previously been
      reported as routine clinical practice, but only as indicated by rejection or
      adverse effects. METHODS: The safety and metabolic outcome of elective conversion
      from tacrolimus to cyclosporin was examined in 19 recipients of cadaver renal
      transplants. Conversion was performed in stable patients at 3-6 months after
      transplantation. RESULTS: Patient and graft survival was 100% at 3 months after
      conversion, with no rejection episodes. Three patients have been subsequently
      converted back to tacrolimus, two for rejection and one for hirsutism. There were
      no significant changes in creatinine, urate, or blood sugar levels after
      conversion, but the mean plasma magnesium rose from 0.73 (0.63-0.97) to 0.82
      (0.65-1) mmol/liter (P=0.037), and the mean plasma cholesterol rose from 5.2 (3.4
      6.8) to 5.5 (3.8-7.6) mmol/liter (P=0.033). Pharmacokinetic profiles were
      measured before and after conversion, and showed that cyclosporin (Neoral)
      exhibited significantly less interpatient and intrapatient variability than
      tacrolimus, for area under the curve (AUC), maximum concentration postdose
      (Cmax), minimum concentration postdose (Cmin), time to maximum concentration
      (Tmax). CONCLUSION: This is the first study that has examined the outcome of
      conversion from tacrolimus- to cyclosporin-based immunosuppression in stable
      patients after renal transplantation. This conversion was performed without early
      immunological hazard, but there was a small rise in blood cholesterol levels
      after conversion. Pharmacokinetic studies showed cyclosporin in the form of
      Neoral showed less inter- and intrapatient variability than tacrolimus, although
      this is of uncertain clinical significance.

PMID- 10919602
TI  - Babesiosis in a renal transplant recipient acquired through blood transfusion.
AB  - BACKGROUND: The success of organ-replacement therapies has resulted in a
      population of chronically immunosuppressed but active people who experience
      increased vulnerability to tick-borne zoonoses. Several of these infections may
      be life threatening. Human babesiosis is an emerging zoonosis that is transmitted
      by the same tick that transmits Lyme disease and human granulocytic ehrlichiosis.
      METHODS: We briefly review these zoonoses and present a case of a renal
      transplant recipient who survived infection by Babesia microti contracted through
      blood transfusion. RESULTS: A recipient of a living-related renal transplant
      developed acute postoperative hemolytic anemia. The etiology of this anemia was
      diagnosed by peripheral red blood cell smear as Babesia microti. The patient was
      managed by a reduction in transplant immunosuppressive therapy and administration
      of clindamycin and quinine antimicrobials. CONCLUSIONS: Transplant patients may
      contract babesiosis after tick exposure and/or via blood transfusion. The
      diagnosis of babesiosis may be confused with malaria and should be included in
      the differential diagnosis of posttransplant hemolytic-uremic syndrome in organ
      transplant patients.

PMID- 10919601
TI  - Glutathione supplementation during cold ischemia does not confer early functional
      advantage in renal transplantation.
AB  - BACKGROUND: Reduced glutathione (GSH), a component of University of Wisconsin
      (UW) solution, is reported to oxidize during storage. Consequently the commercial
      manufacturer of UW recommends the supplemental addition of GSH to UW before
      utilization. We investigated the influence of supplemental GSH during cold
      ischemia on early renal allograft function. METHODS: One hundred kidneys were
      locally procured from heart-beating donors, preserved in our laboratory, and
      transplanted during an 18-month period. Selected donor, preservation, and outcome
      characteristics were collected and compared by presence of supplemental GSH and
      method of preservation. All kidneys were randomized to receive 3.0 mM
      supplemental GSH to perfusate or no supplementation (control) and were preserved
      by either cold storage (CS) in UW or machine perfused (MP) in UW-machine
      perfusate solution (MPS). During MP, perfusion characteristics (flow, resistance,
      perfusate electrolytes, and pH) were serially measured. RESULTS: There were no
      significant differences among the groups when the donor characteristics of age,
      serum creatinine, and intra-operative urine output were compared. Preservation
      characteristics were similar among the groups with the exception of cold ischemia
      time, which was longer in the MP group compared to CS (26.1 h vs. 21.9 h,
      P=0.03). When compared with CS, kidneys preserved by MP exhibited a 33.4%
      increase in immediate function (93% vs. 62%, P=0.01), a corresponding 29.4%
      decrease in the incidence of delayed graft function (10% vs. 34%, P=0.02), and a
      10% improvement in short-term (6-month) graft survival (98% vs. 88%, P=0.02). The
      addition of GSH supplementation to perfusate resulted in no significant
      differences in graft outcomes. CONCLUSIONS: Despite recommendations by the
      manufacturer that UW solution be routinely supplemented with GSH, supplemental
      GSH does not influence early renal allograft function. Our data suggest that a
      far greater beneficial impact on early graft function is achieved by machine
      perfusion. We conclude that GSH supplementation of commercially available UW is
      not necessary.

PMID- 10919604
TI  - Reflex sympathetic dystrophy syndrome of the lower limbs in a renal transplant
      patient treated with tacrolimus.
AB  - BACKGROUND: Recently, a previously unrecognized posttransplant syndrome known as
      reflex sympathetic dystrophy syndrome of the lower limbs has emerged in patients
      receiving cyclosporine as immunosuppression. We describe herein this complication
      observed in a patient treated with tacrolimus after kidney transplantation.
      METHODS: A 49-year-old man received a kidney transplant from a cadaver donor and
      was treated with tacrolimus. Three months later, the patient complained of severe
      pain in the lower limbs that affected both knees and ankles. Bone scintigraphy
      and magnetic resonance were consistent with reflex sympathetic dystrophy
      syndrome. RESULTS: Laboratory tests that included creatinine, glomerular
      filtration rate, calcium, phosphate, urate, alkaline phosphatase, and
      parathormone were normal or near normal. Tacrolimus levels were around 13
      microg/ml. Clinical improvement appeared slowly and spontaneously during the
      following 3 months, without appreciable changes in the tacrolimus level.
      CONCLUSIONS: In kidney transplant patients, tacrolimus could be a risk factor for
      the development of a reflex sympathetic dystrophy syndrome.

PMID- 10919603
TI  - Reversible acute renal allograft dysfunction due to gabapentin.
AB  - BACKGROUND: The use of gabapentin as an effective analgesic agent for neuropathic
      pain has expanded considerably. Its lack of both anticholinergic side effects and
      interference with the metabolism of drugs via the cytochrome P450 pathway make it
      especially useful for transplant recipients. METHODS AND RESULTS: We describe the
      case of a renal transplant recipient with a long-term stable functioning
      allograft who developed reversible acute renal dysfunction after beginning
      gabapentin therapy for chronic pain due to diabetic neuropathy. CONCLUSIONS: We
      suggest that gabapentin may cause acute renal dysfunction by a mechanism
      involving renal afferent vasoconstriction. Caution should be employed when
      considering the use of gabapentin in transplant recipients, especially when
      combined with other agents that may potentiate renal vasoconstriction.

PMID- 10919605
TI  - Donor organ transmission of varicella zoster due to cardiac transplantation.
AB  - BACKGROUND: We report a case of donor-transmitted varicella zoster viral (VZV)
      infection in a cardiac transplant recipient. A 15-month-old girl developed
      primary VZV infection 12 days after cardiac transplantation. The donor suffered
      from varicella 2 weeks before death from pneumococcal meningitis. METHODS:
      Despite treatment of the seronegative recipient with intravenous acyclovir from
      the time of surgery, she developed symptoms of fever, a nonspecific macular rash,
      and small palatal vesicles. RESULTS: After rapid diagnostic confirmation by
      direct immunofluorescence on vesicular fluid, high-dose intravenous acyclovir was
      commenced. In addition, the cyclosporine dose was reduced by 25%. The child made
      a quick and uncomplicated recovery. CONCLUSIONS: Donor organ transmission of VZV
      has not, to our knowledge, been previously reported. It occurred despite
      treatment with acyclovir and resulted in an atypical cutaneous eruption. It
      responded to an increased dose of acyclovir and a reduced level of
      immunosuppression.

PMID- 10919607
TI  - Plasmapheresis: an effective therapy for primary allograft nonfunction after
      liver transplantation.
AB  - BACKGROUND: The role of plasmapheresis in liver failure and hepatic coma remains
      controversial. Also, its use as a salvage strategy for patients with severe
      allograft dysfunction after liver transplantation has not been defined. This
      report reviews the use of plasmapheresis in primary hepatic allograft nonfunction
      (PNF). METHODS: From May of 1997 to October of 1998, five patients underwent
      plasmapheresis for PNF after other causes of immediate allograft dysfunction were
      excluded. These patients underwent two to five plasmapheresis procedures during
      which one plasma volume was removed and replaced with fresh frozen plasma (FFP)
      or with 50% FFP and 50% albumin. RESULTS: All recipients who underwent
      plasmapheresis had restoration of liver function. There was one death from
      pulmonary embolism, for an overall survival rate of 80%. The four surviving
      patients all had functioning allografts 1 year after liver transplantation. In
      contrast, during the same period, there were two patients in whom PNF was treated
      by retransplantation, and both died within 3 months after surgery with
      functioning allografts. CONCLUSIONS: Plasmapheresis provides an effective
      treatment option for PNF immediately after liver transplantation and may obviate
      the need for retransplantation.

PMID- 10919606
TI  - Association of human herpesvirus 7 with cytomegalovirus disease in renal
      transplant recipients.
AB  - BACKGROUND: Recent studies have linked human herpesviruses 6 (HHV-6) and 7 (HHV
      7) with posttransplant cytomegalovirus (CMV) disease. METHODS: Thirty-seven renal
      transplant recipients were monitored weekly for CMV, HHV-6, and HHV-7 DNA and
      serological responses for 12 weeks after transplantation. Plasma CMV load and the
      occurrence of CMV disease was related to HHV-6 and -7 detection. RESULTS: CMV
      disease was identified in 12 patients. In a logistic regression analysis, factors
      significantly associated with CMV disease were the detection of HHV-7 DNA in
      peripheral blood leucocytes and donorrecipient CMV serostatus. Patients with
      detectable HHV-7 DNA had significantly higher peak plasma CMV loads (P=0.01).
      CONCLUSIONS: An association was found between HHV-7, but not HHV-6, DNA detection
      and CMV disease, suggesting a possible role of HHV-7 in its pathogenesis.

PMID- 10919608
TI  - The impact of HLA sensitization and donor cause of death in heart
      transplantation.
AB  - Current expansion of the recipient population and increased utilization of left
      ventricular assist devices as a bridge-to-transplantation have resulted in HLA
      sensitization becoming an increasingly important clinical problem in cardiac
      transplantation. We evaluated the impact of HLA sensitization and donor cause of
      death on survival in 500 cardiac transplant recipients. Donor cause of death was
      grouped into two categories, trauma and nontrauma. Panel reactive antibodies at
      the time of transplant were assayed and used as a marker for sensitization if
      more than 10%. Sensitized recipients had a poorer 1-year survival than those not
      sensitized (76 vs. 89%, respectively, P=0.2). Donor cause of death had an overall
      significant impact on survival with 1-year survival for recipients of trauma
      organs of 92 and 82% for recipients of nontrauma hearts (P=0.02). Trauma hearts
      transplanted into sensitized recipients yielded a survival of 93% at 1 year
      whereas if nontrauma donor hearts were transplanted into these recipients,
      survival was only 52% at 1 year, P<0.001. These intriguing results suggest that
      graft survival in HLA-sensitized recipients could be significantly improved
      through the use of hearts from trauma death donors.

PMID- 10919609
TI  - Atrial conduction disturbance as an indicator of rejection after cardiac
      transplantation.
AB  - BACKGROUND: Abnormalities of the terminal force of the P wave in Lead V1 (ptf-V1)
      and dispersion of corrected atrial repolarization (Ta-TcD) are believed to
      represent interatrial conduction defect. METHODS AND RESULTS: To determine
      whether atrial conduction disturbance correlates with cardiac allograft
      rejection, we analyzed 249 twelve-lead-electrocardiograms, echocardiograms,
      hemodynamic parameters, and endomyocardial biopsys from 137 patients with heart
      transplantation. Both ptf-V1 and Ta-TcD were significantly increased in patients
      with severe, moderate, and mild rejection. In 22 patients, significant increases
      of the ptf-V1 and Ta-TcD were observed before positive histological findings, and
      significantly correlated with severity of rejection during 5- week to 1-year
      follow-up. Increase of 0.030 mm x sec in ptf-V1 or 0.040 s1/2 in Ta-TcD indicated
      cardiac rejection > or =1B with sensitivity of 88 and 83%, specificity of 85 and
      77%, respectively. CONCLUSION: These results suggest that the ptf-V1 and Ta-TcD
      might be an adjunct to detect rejection and reduce the number of surveillance
      EMB.

PMID- 10919610
TI  - Negative immunohistochemical detection of CD103 (alphaEbeta7 integrin) in the
      infiltrates of acute rejection in liver and kidney transplantation.
AB  - BACKGROUND: The infiltration of epithelium by CD8+ T lymphocytes in human renal
      or liver allografts is a critical feature of acute rejection. CD103 expression
      can be acquired in vitro by CD8+ cytotoxic T lymphocytes in response to
      allogeneic renal epithelial cells and promotes their adhesion to epithelium and
      subsequent lysis of epithelial cells. We investigated the expression of CD103 in
      T-cell infiltrates during acute renal or liver rejection (grade < III). METHODS:
      Immunohistochemical detection of CD103 in 11 liver and 10 kidney transplant
      biopsies with histopathological diagnosis of acute rejection. RESULTS: None of
      the infiltrates expressed detectable CD103, although positive controls were
      stained under our conditions. CONCLUSIONS: Failure to detect CD103 in renal
      biopsies can be related to the early posttransplantation interval (<6 months)
      corresponding to a first rejection episode. In our hands, immunohistological
      detection of CD103 was not possible in the infiltrates of acute rejection in
      liver or kidney transplantation.

PMID- 10919611
TI  - Idiopathic giant esophageal ulcers in a renal transplant patient responsive to
      steroid therapy.
AB  - Idiopathic giant esophageal ulcers in immunocompromised patients have been
      described only in patients with acquired immunodeficiency syndrome. A solitary
      report of an idiopathic giant esophageal ulcer in an immunocompetent patient
      exists. We describe a case of idiopathic esophageal ulceration ultimately
      responsive to steroid therapy in a 31-year old immunosuppressed, human
      immunodeficiency virus-negative renal transplant patient. The case is described
      with particular reference to the evaluation, differential diagnosis, and
      therapeutic response to steroids. Similarities in presentation and treatment to
      giant esophageal ulcers in human immunodeficiency virus infection suggest an
      underlying immune defect as the likely cause. This is the first described case of
      giant esophageal ulceration responsive to steroids in an immunosuppressed human
      immunodeficiency virus-negative patient. This entity should be added to the
      differential diagnosis of esophageal ulceration in solid organ transplant
      recipients.

PMID- 10919612
TI  - Fatal transfer of malignant melanoma from multiorgan donor to four allograft
      recipients.
AB  - BACKGROUND: In this report we describe the transfer of malignant melanoma from a
      single donor to four solid organ transplant recipients, all of whom died from
      metastatic melanoma. METHODS AND CASE HISTORIES: The donor of a heart, liver, and
      two kidneys to four separate recipients died of intracerebral hemorrhage. The
      donor had no history or clinical evidence of melanoma. All four recipients,
      treated with standard immunosuppression protocols, developed metastatic malignant
      melanoma within 1 year after transplantation Three patients died within 14 months
      after transplantation, although the fourth, whose immunosuppressive therapy was
      discontinued, died of metastatic melanoma 30 months after renal transplantation.
      FINDINGS: Tumors from all recipients were histologically identical. Donor origin
      of tumor cells was confirmed by polymerase chain reaction (PCR)-based DNA
      analysis for polymorphic short tandem tetrameric repeats (Geneprint STR, Promega
      Corp., Madison, WI). DNAs from nontumorous donor tissue and tumor tissue
      available from three recipients tested positive for CSF1P0 alleles 10 and 12 and
      for TH01 alleles 6 and 7, although DNAs from nonneoplastic recipient tissues all
      exhibited different allelotypes. INTERPRETATION: Transmission of fatal or
      potentially fatal malignant tumors, notably malignant melanoma, from donor to
      recipient is an uncommon complication of solid organ transplantation. PCR-based
      genetic analysis permits definitive assignment of the source of posttransplant
      tumors.

PMID- 10919613
TI  - Prostaglandin E2 induces expression of P-selectin (CD62P) on cultured human
      umbilical vein endothelial cells and enhances endothelial binding of CD4-T-cells.
AB  - Interaction of endothelial P-selectin with sialyl Lewis(x)-glycoprotein or P
      selectin glycoprotein ligand (PSGL)-1 on leukocytes represents an early step in
      leukocyte recruitment. Redistribution of P-selectin to the endothelial cell
      surface occurs rapidly after challenge with several proinflammatory agents, for
      example, histamine, leucopterins, or lipopolysaccharide. We present evidence that
      prostaglandin E2 (PGE2) is an efficient inductor of surface P-selectin on
      cultured human umbilical vein endothelial cells (HUVEC). The increase in P
      selectin-immunoreactivity coincided with redistribution of cytoplasmic P-selectin
      reactive granulae to the endothelial cell surface, as visualized by confocal
      laser microscopic examination. CD4-T-cell adhesion to PGE2-stimulated HUVEC was
      also enhanced by a factor of 4, and blocking mAb directed against the binding
      site of P-selectin almost completely abrogated this increase in CD4-T-cell
      adhesion. In summary, our findings show that liberation of PGE2 is an important
      inductor of P-selectin surface expression on endothelial cells, resulting in
      enhanced recruitment of inflammatory cells.

PMID- 10919615
TI  - The role of mycophenolate mofetil in chickenpox after renal transplantation.

PMID- 10919614
TI  - Posttransplantation weight gain is predominantly due to an increase in body fat
      mass.

PMID- 10919616
TI  - Organ donors with primary central nervous system tumor.
AB  - Patients with primary central nervous system (CNS) tumor have been accepted for
      organ donation because these tumors very rarely spread outside the CNS. However
      several case reports of CNS tumor transferral with organ transplantation recently
      challenged this attitude. Some risk factors for extraneural spread of CNS tumors
      have been determined, but the absence of risk factors does not exclude the
      possibility of metastases. To our knowledge, 13 cases of CNS tumor transferral
      with organ transplantation (one heart, three livers, eight kidneys, one
      kidney/pancreas) have been reported in the literature. Even if no prospective
      evaluation of the CNS tumor transmission risk with transplantation has been
      undergone, this risk may be estimated between a little more than 0% and 3% from
      retrospective series. The authors consider that patients with CNS tumor should be
      accepted as donors as long as the risk of dying on the waiting lists is
      significantly higher than the tumor transferral risk. Therefore the authors would
      have no restriction for transplanting organs from donors with benign or low-grade
      CNS tumor. For high-grade tumors, the authors would consider these donors as
      "marginal donors," and balance the risk of tumor transmission with the medical
      condition of the recipient.

PMID- 10919617
TI  - Questions about the use of organ donors with tumors of the central nervous
      system.

PMID- 10919618
TI  - Clinical comparison of two total ankle replacements.
AB  - We compared the outcome of the cemented Thompson Parkridge Richards (TPR) ankle
      prosthesis with that of the cementless Scandinavian Total Ankle Replacement
      (STAR) ankle prosthesis in a demographically similar group of patients. These
      were 14 consecutive arthroplasties in 12 rheumatoid arthritis patients, all
      operated on by the same surgeon. The status of all patients, five years or more
      after surgery, is known. The mean follow-up periods for the TPR group and the
      STAR group are 7.2 and 5.4 years respectively. Four of the six TPR tibial
      components became radiographically loose within two years of surgery. Two of
      these have been converted to fusions. The STAR prostheses remain satisfactory
      both clinically and radiographically at five years.

PMID- 10919619
TI  - The effects of early mobilization in the healing of achilles tendon repair.
AB  - Twenty-four male New Zealand rabbits underwent suture repair of a tenotomy of the
      left achilles tendon. The rabbits were randomized into two groups of 12 animals;
      in group (A), the ankle was immobilized by pinning for 35 days, while in the
      group (B), the ankle was immobilized for only 14 days followed by active
      mobilization. Following sacrifice at 35 days postoperatively, the retrieved
      tendons were evaluated by biomechanical testing and histologic examination.
      Approximately 50% of stretching occurred in the first four days; average overall
      elongation was 9.5+/-1.0 mm and 12.7+/-1.5 mm (p=0.102) and average stiffness
      recovery was 67.4+/- 2.0% and 82.9 +/- 1.9% (p=0.0004) for groups A and B
      respectively. Histologically both groups demonstrated traces of disorganized neo
      collagen fibers at the repair site as early as the fourth day with subsequent
      appearance of more mature collagen. The results obtained from our study favor
      early mobilization of the repaired tendon, which seems to restore the functional
      properties of the tendons more rapidly than continuous immobilization of an
      identical surgical repair.

PMID- 10919620
TI  - Morton's intermetatarsal neuroma: morphology and histological substrate.
AB  - Twenty-three biopsies from patients with the typical symptoms of intermetatarsal
      neuroma (so-called Morton's metatarsalgia) were compared histologically and semi
      quantitatively with 25 plantar nerves from the intermetatarsal space III/IV
      gained at autopsies from cases where no problems in the forefoot had been
      recorded. The histomorphological examination of the nerves from autopsies
      revealed the same findings as were found in the biopsies. Thus, qualitatively,
      the nerves from patients could not be distinguished from those gained at autopsy.
      The only difference was the diameter of the resected nerves: semi-quantitative
      analysis of the nerves showed that the 17 thinnest ones were all from autopsies
      and the five thickest ones from biopsies of symptomatic patients. At medium
      diameters, however, there was wide overlap of the two groups. The study yielded a
      specificity of the swelling of 80 % and a sensitivity of 78%. From these results
      it must be concluded that diagnostic MRIs or ultrasonography, are unnecessary for
      decision-making about operative treatment and are not superior to exploratory
      local anaesthesia. Since histomorphological findings in intermetatarsal neuroma
      (so far accepted as the gold standard for confirmation of that diagnosis) were
      the same as findings in autopsied (normal) specimens, the value of postoperative
      histological examination is questioned. It merely proved that the nerve has been
      resected.

PMID- 10919621
TI  - Classification and treatment of plantar fibromatosis.
AB  - A retrospective study of 18 patients (23 feet) with plantar fibromatosis who
      required surgical excision between January, 1991, and June, 1998, was performed.
      Subtotal plantar fasciectomy was performed to remove the tumor with a wide
      disease-free margin. 16 patients (21 feet) were interviewed and 14 patients (19
      feet) were examined with an average followup of 36 months. Two patients (2 feet)
      with less than 12 months followup were excluded. Both subjective and objective
      evaluations and pre- and postoperative x-rays were reviewed to assess the
      alignment of the bony arch. There were nine males and nine females, age 49 years,
      average, at the time of diagnosis. Sixty-seven percent of patients had bilateral
      disease, and 28% had associated Dupuytren's contracture. There were 18 primary
      and five recurrent tumors. An operative staging system, I to IV, for plantar
      fibromatosis is presented which incorporates the extent of plantar fascia
      involvement, the presence of skin adherence, and the depth of tumor extension.
      The stage of the tumor correlated well with postoperative wound healing, skin
      necrosis, and recurrence. In fifteen of 21 feet, the patients were satisfied
      without reservations, and in three of 21 feet, they were satisfied with
      reservations. In 18/21 (86%) feet, the patient reported he/she would have surgery
      done again. There were two recurrent tumors. One was reoperated and the patient
      was disease free twelve months postoperatively. The other recurrence was
      asymptomatic 40 months postoperatively and required no treatment. One patient
      required an excision of a postoperative cutaneous neuroma. Eleven of 21 feet
      (52%) experienced delayed healing and of which four required a split thickness
      skin graft. Ten of the eleven feet with delayed wound healing and all four cases
      requiring a skin graft had a stage ill or IV tumor. Pre- and postoperative
      weightbearing radiographs revealed a slight decrease in the calcaneal pitch
      angle, navicular height, and medial cuneiform height indicating a decrease in the
      height of the medial longitudinal arch.

PMID- 10919622
TI  - Magnetic resonance and cadaveric findings of the incidence of plantaris tendon.
AB  - A retrospective review of 63 Magnetic Resonance Image studies (yielding 86
      ankles) was conducted to find the incidence of the plantaris tendon.
      Radiographically, the plantaris tendon was visualized 62.8% of the time. Surgical
      confirmation of this tendon during 18 achilles surgeries yielded 13 "true
      positives" and 4 "true negatives". Sensitivity was 92.8%; specificity and
      positive predictive value was 100%, respectively. As a comparison, forty
      cadaveric specimens were evaluated as well, with the incidence of the plantaris
      found to be 97.5%. These findings may be useful when considering MRIs as a
      screening tool for the presence of plantaris tendon. When axial images were 4 mm
      or less, the plantaris tendon was more easily visualized. A Chi-squared test
      examining for differences of axial sections greater than 4 mm was not
      significant. (P=0.2). This is important if one is to use MRI to screen for the
      plantaris (for graft purposes).

PMID- 10919623
TI  - Deltoid ligament strain after correction of acquired flatfoot deformity by triple
      arthrodesis.
AB  - Deltoid insufficiency represents a difficult surgical challenge. We have
      witnessed patients who have developed a valgus tibiotalar deformity following a
      properly positioned triple arthrodesis. To investigate whether the triple
      arthrodesis itself, by creating a rigid triple joint complex below the ankle,
      leads to increased strain of the deltoid complex, a flatfoot model was created in
      8 fresh-frozen below-knee amputation specimens. Each specimen was loaded in three
      gait cycle (GC) positions: Heel strike (0% GC), midstance (10% GC), and heel rise
      (40% GC). The three components of the ground reaction force (GRF) and the tendon
      forces consistent with those respective positions were applied. To simulate a
      posterior tibial tendon insufficient state the posterior tibial tendon was not
      loaded. Strain at the tibiocalcaneal fibers of the superficial deltoid ligament
      complex was determined at each of the three foot positions. A triple arthrodesis
      was performed and the deltoid strains were again recorded for each position. A
      significant increase in the strain of the deltoid ligament was observed for only
      the heel rise position (p=0.007) in our cadaver model following triple
      arthrodesis. The results favor medializing the calcaneus following arthrodesis to
      protect the deltoid complex.

PMID- 10919624
TI  - Shank rotation: A measure of rearfoot motion during normal walking.
AB  - Motion of the shank in the transverse plane is coupled with pronation and
      supination of the rearfoot, and so its motion relative to the foot can be used as
      an indicator of the pattern of motion in the rearfoot. Compared to the more
      commonly used assessment of motion in the frontal plane between the heel and the
      shank, motion of the shank in the transverse plane relative to the foot provides
      a more complete measure of the pattern of motion of the rearfoot because it
      reflects the motion in all three joints of the rearfoot (the ankle, subtalar
      joint and mid-tarsal joint) not solely the ankle and subtalar components. This
      work aimed to provide normative data for this alternative measure of rearfoot
      function. Data on angular displacement, angular velocity and angular acceleration
      were derived from motion-analysis conducted on 25 subjects. The results suggest a
      difference between the pattern of angular displacement indicated when motion of
      the shank relative to the foot is examined and the pattern of angular
      displacement indicated when motion in the frontal plane between the shank and
      heel is examined. Specifically, the former suggests that resupination of the
      rearfoot after rearfoot pronation during the initial period of gait, starts at
      the beginning of mid-stance, while the latter suggests resupination beginning in
      late mid-stance. Where comparisons were possible, data on the velocity and
      acceleration appeared reasonable and provide further parameters with which to
      investigate the role of motion in the rearfoot in the development of pathologic
      conditions and the effects of intervention on motion in the rearfoot.

PMID- 10919625
TI  - A biomechanical comparison of the Z step-cut and basilar crescentic osteotomies
      of the first metatarsal.
AB  - The basilar crescentic osteotomy is a popular procedure for the correction of
      moderate to severe hallux valgus deformity. Dorsiflexion due to malposition of
      the osteotomy, fixation failure, or late contracture of the soft tissues can lead
      to lateral metatarsalgia. This study compares the mechanical properties of the Z
      step cut osteotomy Scarff to those of the crescentic osteotomy in cantilever
      bending. The ultimate load, maximum bending moment and energy absorbed were
      significantly greater for the Scarff osteotomy compared to those in the
      crescentic osteotomy (p < 0.001). Values for stiffness did not differ between the
      two osteotomies. Failure of the cortical bone-bridge between the screw-hole and
      the osteotomy was observed in all crescentic osteotomies, while fracture of the
      proximal dorsal bridge was seen in all Scarff osteotomies.

PMID- 10919626
TI  - Total contact casting and Keller arthoplasty for diabetic great toe ulceration
      under the interphalangeal joint.
AB  - Interphalangeal (IP) ulcerations of the great toe are frequently encountered in
      neuropathic diabetic feet. While total contact casting is usually effective as a
      first line treatment, recalcitrant ulcers continue to present substantial
      management challenges. The authors retrospectively reviewed the results of Keller
      arthroplasty employed to accelerate ulcer resolution with total contact casting
      in fourteen patients with neuropathic ulcers under the great toe interphalangeal
      (IP) joint that were resistant to casting alone. These data were compared to a
      group of similar patients whose ulcers were successfully treated by non-operative
      measures. No operative complications were observed, and all ulcers healed within
      twenty-four days with no recurrence documented at an average follow-up of 26
      weeks. In cases of resistant great toe IP plantar ulcers associated with hallux
      rigidus that have failed casting trials, this treatment method can be effective.

PMID- 10919627
TI  - Capsuloplasty in hallux valgus surgery.

PMID- 10919628
TI  - Percutaneous CT guided resection of osteoid osteoma of the tibial plafond.
AB  - Osteoid osteomas of the foot and ankle are relatively rare and notoriously
      difficult to diagnose. Juxta-articular osteoid osteomas are more difficult to
      treat and often have a significant delay in diagnosis. We report a case of a
      juxta-articular osteoid osteoma of the tibial plafond. Once the diagnosis was
      made, excisional biopsy was performed percutaneously under computed tomography
      (CT) guidance as an outpatient in the radiology suite. The patient had complete
      resolution of symptoms and remains pain free at two years follow-up. CT guided
      resection can be a lower morbidity and more cost effective technique to treat
      this lesion than traditional methods.

PMID- 10919629
TI  - Closed talar body fracture with talonavicular dislocation; a case report.
AB  - Closed fracture dislocation of the body of the talus is rare. The dislocation of
      the subtalar and ankle joints (associated with fracture body) has been reported
      and already described in the current classifications. We report a case of closed
      fracture of the body of the talus associated with talonavicular dislocation. Open
      reduction and internal fixation was performed after failed attempt of closed
      reduction. The fracture has healed and there is no evidence of avascular necrosis
      after 2 years follow up. We recommend early evaluation of this injury by CT scan
      or by proper radiographic views under sedation and urgent open reduction if one
      attempt at closed reduction has failed.

PMID- 10919630
TI  - The role of the passive structures in the mobility and stability of the human
      ankle joint: a literature review.
AB  - The mobility and stability of the ankle joint have been extensively investigated,
      but many critical important issues still need to be elucidated. However, there
      seems to be a general agreement on several important observations. A more
      isometric pattern of rotation for the calcaneofibular and the tibiocalcaneal
      ligaments with respect to all the others has been reported. Many recent studies
      have found changing positions of the instantaneous axis of rotation, suggesting
      that the hinge joint concept is an oversimplification for the ankle joint. A few
      recent works have also claimed anterior shift of the contact area at the tibial
      mortise during dorsiflexion, which would imply combined rolling and sliding
      motion at this joint. Many findings from the literature support the view of a
      close interaction between the geometry of the ligaments and the shapes of the
      articular surfaces in guiding and stabilizing motion at the ankle joint.

PMID- 10919631
TI  - Guidelines for diabetic foot care.

PMID- 10919632
TI  - Increased pressures in the tarsal tunnel with various foot positions.

PMID- 10919633
TI  - Fractals and cancer.
AB  - Recent studies have shown that fractal geometry, a vocabulary of irregular
      shapes, can be useful for describing the pathological architecture of tumors and,
      perhaps more surprisingly, for yielding insights into the mechanisms of tumor
      growth and angiogenesis that complement those obtained by modern molecular
      methods. This article outlines the basic methods of fractal geometry and
      discusses the value and limitations of applying this new tool to cancer research.

PMID- 10919634
TI  - The Pezcoller lecture: cancer cell cycles revisited.
AB  - Genetic lesions that disable key regulators of G1 phase progression in mammalian
      cells are present in most human cancers. Mitogen-dependent, cyclin D-dependent
      kinases (cdk4 and cdk6) phosphorylate the retinoblastoma (Rb) tumor suppressor
      protein, helping to cancel its growth-inhibitory effects and enabling E2F
      transcription factors to activate genes required for entry into the DNA synthetic
      phase (S) of the cell division cycle. Among the E2F-responsive genes are cyclins
      E and A, which combine with and activate cdk2 to facilitate S phase entry and
      progression. Accumulation of cyclin D-dependent kinases during G1 phase
      sequesters cdk2 inhibitors of the Cip/Kip family, complementing the effects of
      the E2F transcriptional program by facilitating cyclin E-cdk2 activation at the
      G1-S transition. Disruption of "the Rb pathway" results from direct mutational
      inactivation of Rb function, by overexpression of cyclin D-dependent kinases, or
      through loss of p16(INK4a), an inhibitor of the cyclin D-dependent kinases.
      Reduction in levels of p27(Kip1) and increased expression of cyclin E also occur
      and carry a poor prognostic significance in many common forms of cancer. The ARF
      tumor suppressor, encoded by an alternative reading frame of the INK4a-ARF locus,
      senses "mitogenic current" flowing through the Rb pathway and is induced by
      abnormal growth promoting signals. By antagonizing Mdm2, a negative regulator of
      the p53 tumor suppressor, ARF triggers a p53-dependent transcriptional response
      that diverts incipient cancer cells to undergo growth arrest or apoptosis.
      Although ARF is not directly activated by signals that damage DNA, its loss not
      only dampens the p53 response to abnormal mitogenic signals but also renders
      tumor cells resistant to treatment by cytotoxic drugs and irradiation. Lesions in
      the p16--cyclin D-CDK4--Rb and ARF--Mdm2--p53 pathways occur so frequently in
      cancer, regardless of patient age or tumor type, that they appear to be part of
      the life history of most, if not all, cancer cells.

PMID- 10919635
TI  - Human mesothelioma samples overexpress both cyclooxygenase-2 (COX-2) and
      inducible nitric oxide synthase (NOS2): in vitro antiproliferative effects of a
      COX-2 inhibitor.
AB  - Accumulating data demonstrate overexpression of both inducible NO synthase (NOS2)
      and cyclooxygenase-2 (COX2) in many epithelial neoplasias. In addition,
      cyclooxygenase inhibitors have been shown to have antineoplastic and prophylactic
      efficacy against human colon cancer and in mouse models of this disease.
      Mesothelioma arises in a context of asbestos exposure and chronic inflammation,
      which would be expected to enhance the expression of these inducible enzymes.
      This study demonstrates that both inducible enzymes were expressed in 30 human
      mesothelioma tissues but were not detectable in nonreactive mesothelial tissues
      from the same individuals. In contrast, areas of reactive mesothelial cells
      stained positively for these enzymes. In vitro exposure of human mesothelioma
      cell lines to the COX2 inhibitor, NS398, revealed dose- and time-dependent
      antiproliferative activity, whereas the NOS2 inhibitor, 1400W, had no detectable
      inhibitory effect. Surprisingly, nonmalignant human mesothelial isolates
      expressed both NOS2 and COX2 in vitro at the same level as mesothelioma cell
      lines but were less sensitive to NS398 inhibition. This finding indicates that
      these nonmalignant isolates may retain properties of reactive mesothelial cells
      and suggests that targets in addition to COX2 may be involved in the
      antiproliferative response of mesothelioma cell lines. These results have
      clinical significance because of the selective activity of the drug coupled with
      the therapeutic resistance and poor prognosis of mesothelioma. The findings
      presented here suggest that further preclinical studies of these inhibitors in
      animal models of mesothelioma would be of great interest.

PMID- 10919637
TI  - A genome-wide map showing common regions of loss of heterozygosity/allelic
      imbalance in breast cancer.
AB  - We report here a new framework map that integrates data from 143 studies on the
      loss of heterozygosity/allelic imbalance in breast cancer. Full details of these
      loss of heterozygosity maps can be found at the web site
      (http://www.nottingham.ac.uk/pdzmgh/loh/) that accompanies this report. By
      combining results from these data, we have also been able to highlight and
      identify minimum commonly deleted regions on each chromosome. In addition to
      finding commonly deleted regions at both the BRCA1 and BRCA2 loci, which
      confirmed the power of the technique, 24 other regions were identified on 16
      different chromosomes.

PMID- 10919636
TI  - Vaccination against gonadotropin-releasing hormone (GnRH) using toxin receptor
      binding domain-conjugated GnRH repeats.
AB  - A method for the preparation of an immunogen containing multiple copies of a self
      peptide in linear alignment was designed in order to overcome the difficulty of
      inducing an immune response to poorly immunogenic peptide antigens. DNA fragments
      encoding multiple repeats of the self-peptide were generated by a new technique,
      termed template-repeated polymerase chain reaction (TR-PCR), which could be
      subcloned into an expression vector for production of peptide repeats as an
      immunogen. This approach was tested by constructing fusion proteins containing
      the receptor-binding domain of Pseudomonas exotoxin A and multiple copies of the
      10-residue sequence of the peptide hormone gonadotropin-releasing hormone (GnRH).
      Immunization of female rabbits with the immunogen that contained the exotoxin
      receptor-binding domain and 12 copies of GnRH (PEIa-GnRH12) resulted in the
      generation of high-titer antibodies specific for GnRH. Although at equal molar
      basis of the GnRH moiety, the immunogen that contained single copy of GnRH (PEIa
      GnRH1) induced low-titer anti-GnRH antibodies. These observations suggest that
      the presence of multiple peptide repeats is a key factor in eliciting an immune
      response. In addition, anti-GnRH antibodies effectively neutralized GnRH activity
      in vivo, as demonstrated by the degeneration of the ovaries in the injected
      rabbits. Because anti-GnRH antibody could be functionally analogous to GnRH
      antagonist, which has been used to treat patients with ovarian cancer,
      vaccination of PEIa-GnRH12 presents a potential therapeutic application for the
      treatment of GnRH-sensitive ovarian cancer.

PMID- 10919638
TI  - Suppressing effects of dietary supplementation of the organoselenium 1,4
      phenylenebis(methylene)selenocyanate and the Citrus antioxidant auraptene on lung
      metastasis of melanoma cells in mice.
AB  - The modifying effects of the organoselenium 1,4
      phenylenebis(methylene)selenocyanate (p-XSC) and the Citrus antioxidant auraptene
      as dietary supplements on experimental pulmonary metastasis of B16BL6 murine
      melanoma cells were investigated in an i.v. injection model in mice. Seven groups
      of male C57BL/6 mice were fed a basal diet (control group) or the basal diet
      supplemented with p-XSC (4, 8, or 15 mg/kg) or auraptene (250, 500, or 1000
      mg/kg). All mice were fed their respective diet for 2 weeks before and after i.v.
      injection of 1 x 10(5) viable melanoma cells. At termination of the study, the
      incidence of lung metastatic tumors was determined. Cross-sectional areas and
      tumor volumes were analyzed morphometrically. In addition, apoptotic indices of
      lung metastatic tumors of all groups were counted. The incidences of lung
      metastasis in mice fed the diet mixed with 8 or 15 mg p-XSC/kg were significantly
      smaller than that in mice fed the basal diet. The mean numbers of metastatic lung
      tumors were significantly lower in mice fed p-XSC (4, 8, and 15 mg/kg) and
      auraptene (500 and 1000 mg/kg) than in controls. Cross-sectional areas and
      volumes of the tumors were also significantly decreased in mice given p-XSC (8 or
      15 mg/kg) and auraptene (500 mg/kg). Apoptotic indices in mice fed the diets
      mixed with p-XSC (4, 8, or 15 mg/kg) and auraptene (500 and 1000 mg/kg) were
      significantly greater than those in the control group. These results indicate
      that in mice, diet supplementation with p-XSC and auraptene reduces pulmonary
      metastasis of B16BL6 melanoma cells and inhibits the growth of these metastatic
      tumors in lung, in part, by inducing apoptosis. We suggest that these agents,
      especially p-XSC, may be valuable in preventing metastatic diseases in future
      studies in the clinic.

PMID- 10919639
TI  - Synergistic antitumor activity of irinotecan in combination with 5-fluorouracil
      in rats bearing advanced colorectal cancer: role of drug sequence and dose.
AB  - The basis for current clinical trials in the treatment of colorectal cancer with
      the combination of irinotecan (CPT-11) and 5-fluorouracil (FUra) with or without
      leucovorin (LV) is their proven activity as single agents, their different
      mechanisms of action, and lack of CPT-11 cross-resistance to previous FUra/LV
      treatment. The role of drug dose and administration sequence in this combination
      was studied in vivo using a rat colon tumor model (Ward colon carcinoma); we
      administered CPT-11 and FUra by i.v. push once a week for four consecutive weeks
      (weekly x 4), a clinically relevant schedule. The maximum tolerated doses (MTDs)
      of CPT-11 and FUra administered as single agents were 100 mg/kg/week for both
      agents. Three different combination administration sequences were evaluated: (a)
      CPT-11 administered simultaneously with FUra (sequence I); (b) FUra administered
      24 h before CPT-11 (sequence II); and (c) CPT-11 administered 24 h before FUra
      (sequence III). When combining the two drugs at 50% of their respective MTD, the
      antitumor efficacy was sequence dependent with 62, 38, and 95% complete tumor
      regression rate for sequences I, II, and III, respectively. For sequences I and
      II, dose escalation to 75% of the MTD for each drug was paralleled by reversible
      host toxicity with no significant increase in the antitumor activity of the
      combination. With sequence III, however, the combination was lethal in 100% of
      treated animals when the doses of both drugs were at 75% of the MTD or higher.
      With the sequential combination of CPT-11 followed 24 h later by FUra (sequence
      III), the high complete tumor regression rate (cure) could be maintained, even
      when the dose of CPT-11 was reduced to 12.5% of the MTD as long as the doses of
      FUra was kept at 50 -75 % of the MTD. The data demonstrate that the antitumor
      activity and toxicity of combining CPT-11 with FUra is highly sequence dependent
      and that a sequence of CPT-11 preceding FUra is superior with a significant
      increase in the therapeutic index over the other sequences tested. In addition,
      the data also demonstrate that toxicity associated with high dose of CPT-11 can
      be eliminated without loss of the antitumor efficacy by reducing the dose of CPT
      11 to at least 50% of its MTD, whereas the dose of FUra is kept at 50-75 % of its
      MTD.

PMID- 10919640
TI  - Identification of fractalkine, a CX3C-type chemokine, as a direct target of p53.
AB  - Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and
      cytotoxic T cells. Using the differential display method for examining gene
      expression in p53-defective cells transfected by adenovirus containing wild-type
      p53, we observed that fractalkine was induced by ectopic expression of p53. An
      electrophoretic mobility shift assay showed that a potential p53-binding site
      present in the promoter of the fractalkine gene could bind to p53 protein.
      Moreover, a heterogeneous reporter assay indicated that this promoter sequence
      possessed p53-dependent transcriptional activity. The strong induction of
      fractalkine when p53 protein was expressed by a wild-type transgene in p53
      defective cells brought to light a novel role for p53; that is, potential
      elimination of damaged cells by the host immune response system through
      transcriptional regulation of fractalkine. Our results imply a pivotal role of
      p53 in immunosurveillance to prevent cells from undergoing malignant
      transformation.

PMID- 10919641
TI  - Tyrosine 1062 of RET-MEN2A mediates activation of Akt (protein kinase B) and
      mitogen-activated protein kinase pathways leading to PC12 cell survival.
AB  - The RET tyrosine kinase is a functional receptor for neurotrophic ligands of the
      glial cell line-derived neurotrophic factor (GDNF) family. Loss of function of
      RET is associated with congenital megacolon or Hirschsprung's disease, whereas
      germ-line point mutations causing RET activation are responsible for multiple
      endocrine neoplasia type 2 (MEN2A, MEN2B, and familial medullary thyroid
      carcinoma) syndromes. Here we show that the expression of a constitutively active
      RET-MEN2A oncogene promotes survival of rat pheochromocytoma PC12 cells upon
      growth factor withdrawal. Moreover, we show that the RET-MEN2A-mediated survival
      depends on signals transduced by the phosphoinositide 3-kinase (PI3K) and mitogen
      activated protein kinase (MAPK) cascades. Thus, in PC12 cells, RET-MEN2A
      associates with the PI3K regulatory subunit p85 and promotes activation of Akt
      (also referred to as protein kinase B) in a PI3K-dependent fashion; in addition,
      RET-MEN2A promotes MAPK activation. PI3K recruitment and Akt activation as well
      as MAPK activation depend on RET-MEN2A tyrosine residue 1062. As a result,
      tyrosine 1062 of RET-MEN2A is essential for RET-MEN2A-mediated survival of PC12
      cells cultured in growth factor-depleted media.

PMID- 10919642
TI  - Highly selective isolation of unknown mutations in diverse DNA fragments: toward
      new multiplex screening in cancer.
AB  - Cancer research would greatly benefit from technologies that allow simultaneous
      screening of several unknown gene mutations. Lack of such methods currently
      hampers the large-scale detection of genetic alterations in complex DNA samples.
      We present a novel mismatch-capture methodology for the highly efficient
      isolation and amplification of mutation-containing DNA from diverse nucleic acid
      fragments of unknown sequence. To demonstrate the potential of this method,
      heteroduplexes with a single A/G mismatch are formed via cross-hybridization of
      mutant (T-->G) and wild-type DNA-fragment populations. Aldehydes are uniquely
      introduced at the position of mismatched adenines via the Escherichia coli
      glycosylase, MutY. Subsequent treatment with a biotinylated hydroxylamine results
      in highly specific and covalent biotinylation of the site of mismatch. For PCR
      amplification, synthetic linkers are then ligated to the DNA fragments.
      Biotinylated DNA is then isolated and PCR amplified. Mutation-containing DNA
      fragments can subsequently be sequenced to identify type and position of
      mutation. This method correctly detects a single T-->G transversion introduced
      into a 7-kb plasmid containing full-length cDNA from the p53 gene. In the
      presence of a high excess wild-type DNA (1:1000 mutant:normal plasmids) or in the
      presence of diverse DNA fragment sizes, the DNA fragments containing the mutation
      are readily detectable and can be isolated and amplified. The present Aldehyde
      Linker-Based Ultrasensitive Mismatch Scanning has a current limit of detection of
      one base substitution in 7 Mb of DNA and increases the limit for unknown mutation
      scanning by two to three orders of magnitude. Homozygous and heterozygous p53
      regions (G-->T, exon 4) from genomic DNA are also examined, and correct
      identification of mutations is demonstrated. This method should allow large-scale
      detection of genetic alterations in cancer samples without any assumption as to
      the genes of interest.

PMID- 10919643
TI  - Accelerated ultraviolet radiation-induced carcinogenesis in hepatocyte growth
      factor/scatter factor transgenic mice.
AB  - The dramatic rise in incidence of malignant melanoma experienced by populations
      both within the United States and throughout the world over the last several
      decades has been attributed to enhanced exposure to the UV spectrum of sunlight
      radiation. This hypothesis can now be tested using genetically engineered mouse
      models predisposed to malignant melanoma. Here we use melanoma-prone transgenic
      mice inappropriately expressing hepatocyte growth factor/scatter factor (HGF/SF)
      in the skin as an experimental model system to ascertain the consequences of a
      chronic regimen of suberythemal UV radiation on melanoma genesis. HGF/SF is a
      multifunctional regulator capable of stimulating growth, motility, invasiveness,
      and morphogenetic transformation in cells, including melanocytes, expressing its
      receptor tyrosine kinase Met. HGF/SF transgenic mice demonstrate ectopic
      interfollicular localization and accumulation of melanocytes within the truncal
      dermis, epidermis, and junction and if untreated develop primary cutaneous
      melanoma with a mean onset age of approximately 21 months. Transgenic mice and
      their wild-type littermates subjected to UV radiation three times weekly using
      FS40 sunlamps (60% UVB and 40% UVA), with daily UV doses graded from 2.25 to 6.0
      kJ/m2, developed skin tumors with a mean onset age of 26 and 37 weeks,
      respectively (P < 0.001, Kaplan-Meier log rank test). However, the repeated doses
      of suberythemal UV radiation used in this study failed to accelerate melanoma
      genesis, instead inducing the development of nonmelanoma tumors that included
      squamous cell carcinomas, squamous papillomas, and sarcomas. The conspicuous
      absence of melanocytic tumors occurred despite the immunohistochemical detection
      of a significant stimulation (P < 0.001) in melanocyte-specific bromodeoxyuridine
      incorporation in response to only 2 weeks of UV irradiation (total UV dose of
      13.5 kJ/m2), resulting in 2.6- and 4.6-fold increases in the number of
      melanocytes in the dermis and epidermis, respectively. These data indicate that
      chronic suberythemal UV radiation preferentially favors the development of
      nonmelanocytic over melanocytic neoplasms in this transgenic animal, consistent
      with the pathogenesis proposed for sun exposure-associated skin cancer based on
      retrospective studies in the human population. Our findings suggest that the
      HGF/SF transgenic mouse will be useful as an experimental model for determining
      the consequences of exposure to various regimens of UV radiation and for
      elucidating the mechanisms by which such consequences are realized.

PMID- 10919644
TI  - Plasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and
      mammographic density.
AB  - Insulin-like growth factors (IGFs) and insulin-like growth factor-binding
      proteins (IGFBPs) play a role in the normal development of breast tissue and
      possibly in the etiology of breast cancer. Breast density is one of the strongest
      predictors of breast cancer. In a cross-sectional analysis within the Nurses'
      Health Study, we compared the associations of plasma levels of endogenous IGF-I
      and IGFBP-3 with breast density in 65 premenopausal and 192 postmenopausal women.
      The digitized film screen mammograms were evaluated by the computer-assisted
      Toronto method, in which visually selected gray-scale cut points are used to
      assess breast density. Generalized linear models and Spearman's partial
      correlation coefficients described the associations between breast density and
      IGF-I, IGFBP-3, and the IGF-I:IGFBP-3 ratio. Premenopausal breast density was
      positively correlated with IGF-I and inversely correlated with IGFBP-3; the
      association was strongest for the IGF-I:IGFBP-3 ratio and breast density (r =
      0.39; P = 0.004). In contrast, the correlation between breast density and the IGF
      I:IGFBP-3 ratio among postmenopausal women was -0.02 (P = 0.83). The associations
      of IGF-I:IGFBP-3 ratio with breast density differed significantly between
      premenopausal and postmenopausal women (P = 0.01). Mammographic density is
      positively associated with plasma IGF-I levels and inversely associated with
      plasma IGFBP-3 levels among premenopausal women, but not among postmenopausal
      women. These results are consistent with previous studies that showed a positive
      association between a higher IGF-I:IGFBP-3 ratio and subsequent risk of breast
      cancer only among premenopausal women. The findings raise the possibility that
      premenopausal levels of IGF-I and IGFBP-3 could be in the etiological pathway
      that relates higher breast density with increased breast cancer risk.

PMID- 10919646
TI  - Dietary heterocyclic amines and the risk of lung cancer among Missouri women.
AB  - Heterocyclic amines (HCAs) such as 2-amino-3,8-dimethylimidazo[4,5f]quinoxaline
      (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx,), and 2-amino
      1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are found in meats cooked at high
      temperatures. In rodents, MeIQx induces lung tumors. The purpose of this study
      was to investigate lung cancer risk posed by different HCAs in the diet. A
      population-based case-control study of 593 cases and 623 frequency-matched
      controls including both nonsmoking and smoking women was conducted in Missouri.
      An administered food frequency questionnaire with detailed questions on meat
      consumption, degrees of internal doneness, surface browning/charring, and cooking
      technique was linked to a database that provided exposure estimates of three
      HCAs. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were
      calculated using logistic regression. When comparing the 90th and 10th
      percentiles, significant excess risks were observed for MeIQx (OR, 1.5; CI, 1.1
      2.0), but not for DiMeIQx (OR, 1.2; CI, 0.9-1.6) or PhIP (OR, 0.9; CI, 0.8-1.1).
      MeIQx consumption was associated with increased risk of lung cancer for
      nonsmokers (OR, 3.6; CI, 1.3-10.3) and light/moderate smokers (OR, 2.1; CI, 1.3
      3.3), but not for heavy smokers (OR, 1.0; CI, 0.7-1.5). There was elevated risk
      with MeIQx intake for subjects with squamous cell carcinomas (OR, 1.9; CI, 1.2
      3.1) and "other histological cell types" (OR, 1.6; CI, 1.1-2.5), but not for
      subjects with small cell carcinomas and adenocarcinomas. Neither DiMeIQx nor PhIP
      showed an association with smoking categories or lung cancer histology. In
      conclusion, MeIQx may be associated with lung cancer risk, but DiMeIQx and PhIP
      are probably not associated with lung cancer risk.

PMID- 10919647
TI  - Patterns of tumor initiation in choroidal melanoma.
AB  - This study attempts to document the occurrence of tumors with respect to clock
      hour location and distance from the macula and to evaluate tumor location in
      relation to retinal topography and light dose distribution on the retinal sphere.
      Analysis of patterns of tumor initiation may provide new evidence to clarify the
      controversy regarding the possible light-related etiology of choroidal melanoma.
      Incident cases of choroidal and ciliary body melanoma in Massachusetts residents
      diagnosed between 1984 and 1993 were the basis for analysis. Conventional fundus
      drawings and photos were used to assess the initiation site of each tumor. The
      initiation site was defined as the intersect between the largest tumor diameter
      and the largest perpendicular diameter of the tumor. Initiation sites were
      recorded using spherical coordinates. The retinal sphere was divided into 61
      mutually exclusive sectors defined according to clock hour and anteroposterior
      distance from the macula. Rates of initiation were computed for each sector,
      overall, and according to gender and other clinical factors. Results were similar
      in left and right eyes; therefore, these were combined in analysis. Tumor
      initiation had a predilection for the macula (P < 0.0001). Overall, no
      significant clock hour preference was observed (P = 0.63). However, the
      parafoveal zone showed a strong circular trend (P < 0.01), with highest rates
      occurring in the temporal region, and the lowest rates occurring in the nasal
      region. Rates of occurrence in six progressively more anterior concentric zones
      (designated as the foveal, parafoveal, posterior, peripheral, anterior, and
      ciliary body zones) were 21.4, 14.2, 12.1, 8.9, 4.5, and 4.3 counts per spherical
      unit per 1000 eyes, respectively. Concentric zone location did not vary by gender
      (P = 0.93) or laterality (P = 0.78). However, posterior location was associated
      with light iris color (P = 0.01). Tumor diameters were largest in the peripheral
      region of the fundus and smallest in the macular and ciliary body zone (P <
      0.001). Clock hour location was not influenced by gender (P = 0.74), laterality
      (P = 0.53), iris color (P = 0.84), or tumor diameter (P = 0.73). Results suggest
      that tumor initiation is not uniformly distributed, with rates of occurrence
      concentrated in the macular area and decreasing monotonically with distance from
      the macula to the ciliary body. This pattern is consistent with the retinal
      topography and correlates positively with the dose distribution of solar light on
      the retinal sphere.

PMID- 10919645
TI  - Cigarette smoking, CYP1A1 MspI and GSTM1 genotypes, and colorectal adenomas.
AB  - Cigarette smoking has been related to increased risk of colorectal adenomas, but
      the underlying mechanisms are unknown. Genetic polymorphisms are known for
      enzymes involved in the activation of polycyclic aromatic hydrocarbons and other
      tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by
      cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We
      investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of
      colorectal adenomas with special reference to interaction with cigarette smoking
      among 205 cases of colorectal adenomas and 220 controls with normal total
      colonoscopy in a male Japanese population. Cigarette smoking was strongly
      associated with increased risk of colorectal adenomas. Overall, neither the
      CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A
      significant trend for increased risk of colorectal adenomas associated with
      smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing
      trends did not differ by MspI genotype. The positive association between smoking
      and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and
      current smokers, adenoma risk did not differ according to the combination of
      CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to
      modify the risk of colorectal adenomas associated with cigarette smoking.

PMID- 10919648
TI  - Combination of the bioreductive drug tirapazamine with the chemotherapeutic
      prodrug cyclophosphamide for P450/P450-reductase-based cancer gene therapy.
AB  - Tirapazamine (TPZ) is a bioreductive drug that exhibits greatly enhanced
      cytotoxicity in hypoxic tumor cells, which are frequently radiation-resistant and
      chemoresistant. TPZ exhibits particularly good activity when combined with
      alkylating agents such as cyclophosphamide (CPA). The present study examines the
      potential of combining TPZ with CPA in a cytochrome P450-based prodrug activation
      gene therapy strategy. Recombinant retroviruses were used to transduce 9L
      gliosarcoma cells with the genes encoding P450 2B6 and NADPH-P450 reductase.
      Intratumoral coexpression of P450 2B6 with P450 reductase sensitized 9L tumor
      cells to CPA equally well under normoxic (19.6% O2) and hypoxic (1% O2)
      conditions. The P450 2B6/P450 reductase combination also sensitized 9L tumor
      cells to TPZ under both culture conditions. Interestingly, bystander cytotoxic
      effects were observed for both CPA and TPZ under hypoxia. Furthermore, TPZ
      exerted a striking growth-inhibitory effect on CPA-treated 9L/2B6/P450 reductase
      cells under both normoxia and hypoxia, which suggests the utility of this drug
      combination for P450-based gene therapy. To evaluate this possibility, 9L tumor
      cells were transduced in culture with P450 2B6 and P450 reductase and grown as
      solid tumors in severe combined immune deficient mice in vivo. Although these
      tumors showed little response to TPZ treatment alone, tumor growth was
      significantly delayed, by up to approximately four doubling times, when TPZ was
      combined with CPA. Some toxicity from the drug combination was apparent, however,
      as indicated by body weight profiles. These findings suggest the potential
      benefit of incorporating TPZ, and perhaps other bioreductive drugs, into a
      P450/P450 reductase-based gene therapy strategy for cancer treatment.

PMID- 10919649
TI  - In vivo site specificity and human isoenzyme selectivity of two topoisomerase II
      poisoning anthracyclines.
AB  - Anthracyclines exert antitumor activity by stimulating site-selective DNA
      cleavage by topoisomerase II (top2). DNA cleavage sites stimulated by two
      anthracycline analogues, dh-EPI and da-IDA, were investigated at the histone gene
      cluster of cultured Drosophila Kc cells. The two agents stimulated analogue
      specific patterns of double-stranded DNA cleavage in Kc cell chromatin. Analyses
      of 47 base sequences of dh-EPI sites showed that the analogue largely followed
      the in vitro selectivity rule, the requirement of (5')TA at 3' ends of cleaved
      strands. da-IDA was more selective than dh-EPI, and thus fewer sites could be
      collected. Nevertheless, base sequences were consistent with its in vitro base
      preferences. DNA cleavage was then studied in vitro with Drosophila and human
      top2 isoforms. The tested drugs stimulated distinct in vitro patterns that
      corresponded to the in vivo patterns. Human top2alpha promoted cleavage patterns
      that were much more similar to those of Drosophila top2 (both in vitro and in
      vivo) than human top2beta. Moreover, da-IDA showed a marked site-dependent
      preference for human top2beta. Thus, DNA site selection in vivo is different for
      the test anthracyclines, and together with a degree of beta-form specificity, may
      affect drug activity in human cells.

PMID- 10919650
TI  - Cooperative effects of Mycobacterium tuberculosis Ag38 gene transduction and
      interleukin 12 in vaccination against spontaneous tumor development in proto-neu
      transgenic mice.
AB  - An approach to stimulating an immune response against tumors is to transduce
      tumor cells with bacterial genes, which represent a "danger signal" and can
      induce a wide immune response. Mycobacterium tuberculosis genes and their encoded
      proteins play a pivotal role in linking innate and cell-mediated adaptive
      immunity and represent ideal candidates as immune adjuvants for tumor vaccines.
      The efficacy of a cancer vaccine, obtained by transduction of a mammary tumor
      cell line with the M. tuberculosis Ag38 gene, was investigated in female mice
      transgenically expressing the rat HER-2/neu proto-oncogene. These mice
      spontaneously develop stochastic mammary tumors after a long latency period. The
      onset of spontaneous mammary tumors was significantly delayed in mice vaccinated
      with Ag38-transduced cells but not in mice vaccinated with nontransduced cells as
      compared with untreated mice. Protection from spontaneous tumor development was
      increased when mice were vaccinated with the mycobacterium gene-transduced
      vaccine plus a systemic administration of interleukin 12 (IL-12) at a low dose.
      Mice vaccinated with nontransduced cells plus IL-12 developed tumors, with only a
      slight delay in tumor appearance as compared with the control group. Lymphocytes
      obtained from lymph nodes of mice vaccinated with transduced cells secreted high
      levels of IFN-gamma. CD3+CD8+ spleen cells derived from these mice responded to
      the tumor with IFN-gamma production. These data indicate the efficacy of a short
      term protocol of vaccinations exploiting the adjuvant potency of a M.
      tuberculosis gene and low doses of IL-12 in a model of stochastic development of
      mammary tumors. This adjuvant approach may represent a promising
      immunotherapeutic strategy for cancer immunization.

PMID- 10919651
TI  - Prevention of mammary tumors with a chimeric HER-2 B-cell epitope peptide
      vaccine.
AB  - Synthetic peptide vaccines targeting B-cell epitopes of the extracellular domain
      of the HER-2 oncoprotein were evaluated for their capacity to elicit HER-2
      specific antibodies with antiproliferative activity. Several HER-2 B-cell
      epitopes were identified by computer-aided analysis of protein antigenicity, and
      selected B-cell epitopes were synthesized colinearly with a promiscuous T-helper
      epitope (208-302) derived from the measles virus fusion protein at either the NH2
      or COOH terminus linked via a four-residue turn sequence (GPSL). In addition, one
      epitope sequence, 628-647, was mutated to optimize disulfide pairing to mimic the
      native HER-2 receptor. All of the four selected epitopes elicited high-titered
      antibodies in outbred rabbits with exceptionally high titers for MVF-HER-2(628
      647). These antibodies were cross-reactive with the native HER-2 receptor.
      Antibodies elicited by MVF HER-2(628-647) inhibited proliferation of human HER-2
      overexpressing breast cancer cells in vitro and caused their antibody-dependent
      cell-mediated cytotoxicity. Furthermore, immunization with MVF-HER-2(628-647)
      prevented the spontaneous development of HER-2/neu-overexpressing mammary tumors
      in 83% of transgenic mice. The engineered, chimeric peptide B-cell immunogen MVF
      HER-2(628-647) may have applications in the prevention of HER-2-overexpressing
      cancers.

PMID- 10919652
TI  - Antigene and antiproliferative effects of a c-myc-targeting phosphorothioate
      triple helix-forming oligonucleotide in human leukemia cells.
AB  - The c-myc gene is frequently deregulated and overexpressed in human cancers, and
      strategies designed to inhibit c-myc expression in cancer cells may have
      considerable therapeutic value. The purpose of the present work was to
      characterize the antigene and antiproliferative activity of a triple helix
      forming oligonucleotide (TFO) targeted to a homopurine-homopyrimidine sequence in
      the P2 promoter of the c-myc gene. The TFO was synthesized with phosphorothioate
      (PS) internucleotide linkages to confer resistance to intra- and extracellular
      nucleases. This property is required of oligonucleotides designed for in vivo
      testing and therapeutic applications. The PS-TFO was found to form triplex DNA
      with affinity and specificity comparable with that of the corresponding
      phosphodiester TFO, as shown by gel mobility shift and footprinting assays.
      Fluorescence microscopy and polyacrylamide gel analysis showed that the
      fluorescein-labeled PS-TFO accumulated in nuclei of CEM leukemia cells and
      remained intact for at least 72 h. Incubation of CEM cells with PS-TFO reduced c
      myc RNA and protein levels. A single exposure of leukemia cells to the PS-TFO was
      sufficient to induce dose-dependent growth inhibitory effects. Growth inhibition
      correlated with accumulation of cells in S phase and with induction of cell death
      by apoptosis. The PS-TFO was also effective in other leukemia and lymphoma cell
      lines. Control oligonucleotides had minimal effects in all assays. These data
      indicate that the c-myc-targeted PS-TFO is an effective antigene and
      antiproliferative agent, with potential for testing in vivo as a novel approach
      to cancer therapy.

PMID- 10919653
TI  - Use of phosphorous-31 nuclear magnetic resonance spectroscopy to determine safe
      timing of chemotherapy after hepatic resection.
AB  - Liver resection induces accelerated growth of residual hepatic micrometastases.
      Adjuvant chemotherapy may improve outcome if administered early after resection
      but may prove lethal if initiated prior to completion of DNA synthesis in
      regenerating liver. This study investigates phosphorus-31 nuclear magnetic
      resonance ((31)P-NMR) as a noninvasive tool for measuring energy changes
      reflective of hepatic DNA synthesis and for predicting safe timing of
      chemotherapy after 70% hepatectomy. To evaluate metabolic changes in regenerating
      liver, quantitative three-dimensional (31)P-NMR was performed, using the
      technique of chemical shift imaging at various time points after 70% hepatectomy
      in adult male Fischer rats. Animals receiving a course of 2'-deoxy-5
      fluorouridine (FUDR; 100 mg/kg, i.p. four times per day x 5), initiated at the
      time of operation, were also evaluated to observe the effects of chemotherapy on
      liver regeneration. Forty-eight hours after resection, hepatic nucleoside
      triphosphate (NTP), which reflects ATP content, fell 37% (P < 0.03) in animals
      undergoing hepatectomy alone. By contrast, animals receiving FUDR after
      hepatectomy demonstrated a mitigated NTP response, with a drop of only 17% (P =
      not significant), suggesting that interruption of DNA synthesis leads to a
      reduced consumption of ATP. Direct measures of DNA synthesis and nuclear
      proliferation were correlated with NMR findings. [(3)H]Thymidine incorporation
      and Ki67 immunohistochemistry were performed on liver samples from rats
      undergoing 70% hepatectomy with and without FUDR. Both [(3)H]thymidine
      incorporation and Ki67 expression were inhibited significantly at 48 h in animals
      receiving hepatectomy and FUDR, compared with those not treated with FUDR. To
      determine whether NMR changes could be used to identify safe timing of
      chemotherapy after hepatectomy, rats were treated with a 5-day course of FUDR
      initiated either prior to or after NMR changes normalized. Animals treated with
      FUDR at the point of NTP normalization (72 h) showed significantly improved
      survival over those that began treatment at operation (75 % versus 17 %; P =
      0.0005, log rank test). FUDR inhibits hepatic DNA synthesis and influences
      mortality if administered too early after hepatectomy. Chemical shift imaging is
      a noninvasive tool that can identify metabolic changes coinciding with DNA
      synthesis and nuclear proliferation after hepatectomy. (31)P-NMR may be useful
      for determining safe timing of chemotherapy after liver resection.

PMID- 10919654
TI  - Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen
      independent, metastatic human prostate adenocarcinoma cells.
AB  - Cardiac glycosides are used clinically to increase contractile force in patients
      with cardiac disorders. Their mechanism of action is well established and
      involves inhibition of the plasma membrane Na+/K+-ATPase, leading to alterations
      in intracellular K+ and Ca(2+) levels. Here, we report that the cardiac
      glycosides oleandrin, ouabain, and digoxin induce apoptosis in androgen
      independent human prostate cancer cell lines in vitro. Cell death was associated
      with early release of cytochrome c from mitochondria, followed by proteolytic
      processing of caspases 8 and 3. Oleandrin also promoted caspase activation,
      detected by cleavage poly(ADP-ribose) polymerase and hydrolysis of a peptide
      substrate (DEVD-pNA). Comparison of the rates of apoptosis in poorly metastatic
      PC3 M-Pro4 and highly metastatic PC3 M-LN4 subclones demonstrated that cell death
      was delayed in the latter because of a delay in mitochondrial cytochrome c
      release. Single-cell imaging of intracellular Ca(2+) fluxes demonstrated that the
      proapoptotic effects of the cardiac glycosides were linked to their abilities to
      induce sustained Ca(2+) increases in the cells. Our results define a novel
      activity for cardiac glycosides that could prove relevant to the treatment of
      metastatic prostate cancer.

PMID- 10919655
TI  - In vivo cancer gene therapy by adenovirus-mediated transfer of a bifunctional
      yeast cytosine deaminase/uracil phosphoribosyltransferase fusion gene.
AB  - Direct transfer of prodrug activation systems into tumors was demonstrated to be
      an attractive method for the selective in vivo elimination of tumor cells.
      However, most current suicide gene therapy strategies are still handicapped by a
      poor efficiency of in vivo gene transfer and a limited bystander cell killing
      effect. In this study, we describe a novel and highly potent suicide gene derived
      from the Saccharomyces cerevisiae cytosine deaminase (FCY1) and uracil
      phosphoribosyltransferase genes (FUR1). This suicide gene, designated FCU1,
      encodes a bifunctional chimeric protein that combines the enzymatic activities of
      FCY1 and FUR1 and efficiently catalyzes the direct conversion of 5-FC, a nontoxic
      antifungal agent, into the toxic metabolites 5-fluorouracil and 5-fluorouridine
      5'monophosphate, thus bypassing the natural resistance of certain human tumor
      cells to 5-fluorouracil. Unexpectedly, although the uracil
      phosphoribosyltransferase activity of FCU1 was equivalent to that encoded by
      FUR1, its cytosine deaminase activity was 100-fold higher than the one encoded by
      FCY1. As a consequence, tumor cells transduced with an adenovirus expressing FCU1
      (Ad-FCU1) were sensitive to concentrations of 5-FC 1000-fold lower than the ones
      used for cells transduced with a vector expressing FCY1 (Ad-FCY1). Furthermore,
      bystander cell killing was also more effective in cells transduced with Ad-FCU1
      than in cultures infected with Ad-FCY1 or Ad-FUR1, alone or in combination.
      Finally, intratumoral injections of Ad-FCU1 into allo- or xenogeneic tumors
      implanted s.c. into mice, with concomitant systemic administration of 5-FC, led
      to substantial delays in tumor growth. These unique properties make of the FCU1/5
      FC prodrug activation system a novel and powerful candidate for cancer gene
      therapy strategies.

PMID- 10919656
TI  - Dietary flavone is a potent apoptosis inducer in human colon carcinoma cells.
AB  - Flavonoids are polyphenolic compounds that occur ubiquitously in plants. They are
      discussed to represent cancer preventive food components in a human diet that is
      rich in fruits and vegetables. To understand the molecular basis of the putative
      anticancer activity of flavonoids, we investigated whether and how the core
      structure of the flavones, 2-phenyl-4H-1-benzopyran-4-one (flavone) affects
      proliferation, differentiation, and apoptosis in HT-29 human colon cancer cells.
      Moreover, the effects of flavone in transformed epithelial cells were compared
      with those obtained in nontransformed primary mouse colonocytes. Proliferation,
      differentiation, and apoptosis in transformed as well as nontransformed colon
      cells were measured by fluorescence-based techniques. Apoptosis was also
      determined by changes in membrane permeability, FACScan analysis, and detection
      of DNA fragmentation. Semiquantitative reverse transcription PCR was performed to
      assess the effects of flavone on transcript levels. Flavone was found to reduce
      cell proliferation in HT-29 cells with an EC(50) value of 54.8 +/- 1.3 microM and
      to potently induce differentiation as well as apoptosis. The flavonoid proved to
      be a stronger apoptosis inducer than the clinically established antitumor agent
      camptothecin. The effects of flavone in HT-29 cells were associated with changed
      mRNA levels of cell-cycle- and apoptosis-related genes including cyclooxygenase-2
      (COX-2), nuclear transcription factor kappaB (NF-kappaB), and bcl-X(L). Moreover,
      flavone, but not camptothecin, displayed a high selectivity for the induction of
      apoptosis and of growth inhibition only in the transformed colonocytes. In
      conclusion, the plant polyphenol flavone induces effectively programmed cell
      death, differentiation, and growth inhibition in transformed colonocytes by
      acting at the mRNA levels of genes involved in these processes. Because these
      genes play a crucial role in colon carcinogenesis, flavone may prove to be a
      potent new cytostatic compound with improved selectivity toward transformed
      cells.

PMID- 10919657
TI  - In situ tumor vaccination with interleukin-12-encapsulated biodegradable
      microspheres: induction of tumor regression and potent antitumor immunity.
AB  - An alternative technology for the local and sustained delivery of cytokines to
      tumors for cancer immunotherapy was evaluated and shown here to induce tumor
      regression, suppression of metastasis, and development of systemic antitumor
      immunity. Treatment of tumor-bearing BALB/c mice with a single intratumoral
      injection of biodegradable polylactic acid microspheres loaded with recombinant
      interleukin-12 (IL-12) promoted complete regression of the primary tumor and
      prevented the metastatic spread to the lung. Mice that experienced tumor
      regression after being treated rejected a subsequent challenge with live tumor
      cells, which indicated the development of systemic antitumor immunity. In situ
      tumor vaccination, ie., injection of IL-12 microspheres into existing tumors, was
      superior to vaccination of mice with mixtures of tumor cells (live or irradiated)
      and IL-12 microspheres in inducing systemic antitumor immunity. The sustained
      release of IL-12 from the microspheres was superior to bolus injection of free IL
      12, and intratumoral delivery of microspheres was more effective than other
      routes of administration. These studies establish the utility of biodegradable
      polymer microspheres as a clinically feasible alternative to systemic cytokine
      therapy and cytokine gene-modified cell vaccines for the treatment of neoplastic
      disease.

PMID- 10919658
TI  - Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator
      protein-1, and c-Jun NH2-terminal kinase.
AB  - Agents that can suppress the activation of nuclear factor-kappaB (NF-kappaB) and
      activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation.
      Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium
      oleander, is a candidate NF-kappaB and AP-1 modulator. We investigated the effect
      of oleandrin on NF-kappaB activation induced by inflammatory agents. Oleandrin
      blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB in a
      concentration- and time-dependent manner. This effect was mediated through
      inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF
      kappaB. A proprietary hot water extract of oleander (Anvirzel) also blocked TNF
      induced NF-kappaB activation; subsequent fractionation of the extract revealed
      that this activity was attributable to oleandrin. The effects of oleandrin were
      not cell type specific, because it blocked TNF-induced NF-kappaB activation in a
      variety of cells. NF-kappaB-dependent reporter gene transcription activated by
      TNF was also suppressed by oleandrin. The TNF-induced NF-kappaB activation
      cascade involving TNF receptor 1/TNF receptor-associated death domain/TNF
      receptor-associated factor 2/NF-kappaB-inducing kinase/IkappaBalpha kinase was
      interrupted at the TNF receptor-associated factor 2 and NF-kappaB-inducing kinase
      sites by oleandrin, thus suppressing NF-kappaB reporter gene expression.
      Oleandrin blocked NF-kappaB activation induced by phorbol ester and
      lipopolysaccharide. Oleandrin also blocked AP-1 activation induced by TNF and
      other agents and inhibited the TNF-induced activation of c-Jun NH2-terminal
      kinase. Overall, our results indicate that oleandrin inhibits activation of NF
      kappaB and AP-1 and their associated kinases. This may provide a molecular basis
      for the ability of oleandrin to suppress inflammation and perhaps tumorigenesis.

PMID- 10919659
TI  - Identification on a human sarcoma of two new genes with tumor-specific
      expression.
AB  - Genes MAGE, BAGE, GAGE, and LAGE-1/NY-ESO-1 code for antigens that are recognized
      on melanoma cells by autologous CTLs. Because the pattern of expression of these
      genes results in the presence of antigens on many tumors of various histological
      types and not on normal tissues, these antigens qualify for cancer immunotherapy.
      To identify new genes with tumor-specific expression, we applied a cDNA
      subtraction approach, ie., representational difference analysis, to a human
      sarcoma cell line. We obtained two cDNA clones that appeared to be tumor
      specific. The corresponding genes were named SAGE and HAGE because they have the
      same pattern of expression as genes of the MAGE family. SAGE encodes a putative
      protein of 904 amino acids and shows no homology to any recorded gene. Like the
      MAGE-A genes, it is located in the q28 region of chromosome X. Expression of gene
      SAGE was observed mainly in bladder carcinoma, lung carcinoma, and head and neck
      carcinoma but not in normal tissues, with the exception of testis. Gene HAGE,
      which is located on chromosome 6, encodes a putative protein of 648 amino acids.
      This protein is a new member of the DEAD-box family of ATP-dependent RNA
      helicases. Gene HAGE is expressed in many tumors of various histological types at
      a level that is 100-fold higher than the level observed in normal tissues except
      testis. Because of this tumor-specific expression, genes SAGE and HAGE ought to
      encode antigens that could be useful for antitumoral therapeutic vaccination.

PMID- 10919660
TI  - The extracellular region of heregulin is sufficient to promote mammary gland
      proliferation and tumorigenesis but not apoptosis.
AB  - Heregulin (HRG) is a member of the neuregulin family of ligands that have been
      shown to interact with and activate erbB receptors. A transgenic mouse model in
      which full-length HRG is overexpressed has proven that this protein can induce
      carcinomas in the murine mammary gland. These tumors display a high level of
      apoptosis, which appears to be mediated by the cytoplasmic domain of HRG. Because
      both proliferation and apoptosis play a role in tumor formation, we wished to
      separately view those perturbations by removing the suspected apoptosis-inducing
      cytoplasmic domain of HRG. We thereby sought to determine whether overexpression
      of the extracellular region of HRG would be sufficient to induce mammary gland
      carcinomas. A HRG construct lacking the cytoplasmic domain was targeted to the
      mammary gland using the murine mammary tumor virus promoter. Multiple lines of
      transgenic mice carrying the transgene developed mammary gland tumors at
      approximately 15 months of age. These tumors did not display high levels of
      apoptosis as compared with tumors from murine mammary tumor virus/full-length HRG
      transgenic animals. In addition, virgin transgenic mice show a persistence of
      terminal end bud structures, which normally disappear at the onset of puberty in
      wild-type mice. To examine the signal transduction pathway activated by
      extracellular HRG in tumors, we investigated the phosphorylation status of the
      epidermal growth factor receptor family members. Western blot analysis showed
      activation of ErbB2 and ErbB3, suggesting a possible mode of action of
      extracellular HRG in mammary gland carcinomas. We conclude that the extracellular
      and transmembrane domains of HRG are sufficient for the induction of
      tumorigenesis but that induction of apoptosis requires the cytoplasmic tail.

PMID- 10919661
TI  - Different combinations of genetic/epigenetic alterations inactivate the p53 and
      pRb pathways in invasive human bladder cancers.
AB  - Inactivation of both the pRb (pRb-cyclin D1/cyclin-dependent kinase 4/6-p16) and
      p53 (p53-p21(WAF1)-p14(ARF)) pathways is thought to be essential for
      immortalization in vitro and malignant transformation in vivo. We identified
      different combinations of pRb and p53 pathway alterations in 12 invasive
      transitional cell carcinomas (TCCs) and addressed the functional significance of
      the different combinations observed. Results showed four combinations of
      alterations including -pRb/-p53 (ie., pRb inactivated in the pRb pathway and p53
      inactivated in the p53 pathway; four TCCs), -p16/-p53 (four TCCs), -p16/
      p21(WAF1) (one TCC), and -p16/ -p14(ARF) (two TCCs). These groups include two new
      combinations (ie., -p16/-p53 and -p16/-p21(WAF1)) not reported previously for
      TCCs. An alteration in the key components of the p53 pathway was not detected in
      one invasive TCC that had inactivated p16. Note that all four TCCs with
      inactivated pRb had mutant p53; thus, the combinations of -pRb/ -p21(WAF1) and 
      pRb/-p14(ARF) were not observed. Only two of eight TCCs with altered p16 had
      concomitant p14(ARF) loss, demonstrating that simultaneous inactivation of these
      two 9p21INK4a tumor suppressor genes is not obligatory. To determine the
      biological phenotypes of TCCs with different combinations of pRb and p53 pathway
      alterations, their downstream responses to gamma radiation were studied in vitro.
      As expected, none of eight TCCs with mutant p53 responded to gamma radiation by
      elevation of p53, p21(WAF1), or mdm2 or by cell cycle arrest. Only two of four
      TCCs with wild-type p53 and wild-type pRb (the combination of -p16/-p14(ARF))
      showed normal downstream responses to gamma radiation and underwent cell cycle
      arrest. Two TCCs with wild-type pRb and wild-type p53 (the combination of -pl6/
      p21(WAF1) and one TCC with -p16) failed to show cell cycle arrest in response to
      radiation. This was attributed to the absence of p21(WAF1) in one TCC. In
      summary, these data support a model of invasive bladder cancer pathogenesis in
      which both the pRb and p53 pathways are usually inactivated and the biology of
      the tumor is impacted by the mechanism of their inactivations.

PMID- 10919662
TI  - The human T-cell transcription factor-4 gene: structure, extensive
      characterization of alternative splicings, and mutational analysis in colorectal
      cancer cell lines.
AB  - The human T cell transcription factor-4 (hTCF-4) interacts functionally with beta
      catenin in the Wnt signaling pathway, which regulates many developmental
      processes. Moreover, inappropriate reactivation of this pathway attributable to
      APC or beta-catenin mutations has been described in colorectal cancers. Because
      only the human TCF-4 cDNA sequence was known, we determined its genomic
      structure. A total of 17 exons, of which 5 were alternative, were identified.
      Moreover, four alternative splice sites were observed either experimentally or in
      silico by a BLAST approach in expressed sequence tag databases. The alternative
      use of three consecutive exons localized in the 3' part of the hTCF-4 gene
      changes the reading frames used in the last exon, leading to the synthesis of a
      number of hTCF-4 isoforms with short, medium, or long-size COOH-terminal ends. We
      next screened the entire hTCF-4 gene for mutations in a series of 24 colorectal
      cancer cell lines by denaturing gradient gel electrophoresis and/or direct
      sequencing. Besides an already described deletion of an A in an (A)9 coding
      repeat in four cases, we found DNA variants in eight cases for a total of 12
      variants, of which 8 were coding. These include one frameshift mutation in the
      beta-catenin binding domain (exon 1), and one missense mutation in exon 4. In the
      remaining six cases, nonsense or frameshift mutations were localized in the 3'
      part of the gene. These latter alterations have as a common consequence to
      decrease the proportion of the long COOH-terminal hTCF-4 isoform, which contains
      two binding domains for c-terminal binding protein, a protein implicated in the
      repression of the TCF family transcriptional activity. Thus, loss of the TCF-4
      capacity to interact with COOH-terminal binding protein could be an important
      event during colorectal carcinogenesis by modifying Wnt signaling.

PMID- 10919663
TI  - Deletion at 13q21 is associated with aggressive prostate cancers.
AB  - Previous cytogenetic and molecular genetic analyses suggest that the q21 band of
      chromosome 13 harbors a tumor suppressor gene(s) involved in prostatic
      carcinogenesis. The precise genetic location, however, has not been defined. In
      this study, we examined prostate cancer specimens and cell lines/xenograft for
      genetic deletions at 13q21, using the methods of tissue microdissection and
      duplex PCR. Deletions at 13q21 were detected in 13 of 147 (9%) prostate cancer
      samples. Deletion of the same region was also detected in the LNCaP cell line and
      the PC-82 xenograft of prostate cancer. The overlapping region of deletion in
      LNCaP and PC-82 spans 3.1 cM or 2.9 cR, which is equivalent to 1-3 Mb. The
      endothelin receptor B gene, a possible tumor suppressor gene at 13q21, was not
      located in the region of deletion. Among the 13 prostate neoplasms with deletion
      at 13q21, 5 were metastases, and 7 were poorly differentiated primary tumors. The
      only primary tumor that was not poorly differentiated but had deletion occurred
      in one of the youngest patients (49 years) at diagnosis. These results provide
      evidence that 13q21 may harbor an unidentified gene(s) whose inactivation occurs
      in some aggressive carcinomas of the prostate. In addition, this study provides a
      framework for the cloning and identification of the 13q21 gene(s).

PMID- 10919664
TI  - Genome-wide search for loss of heterozygosity using laser capture microdissected
      tissue of breast carcinoma: an implication for mutator phenotype and breast
      cancer pathogenesis.
AB  - Breast cancer is considered to display a high degree of intratumor heterogeneity,
      without any obvious morphological and pathological steps to define sequential
      evolution, and its progression may vary among individual tumors. In an attempt to
      elucidate these etiological and phenotypic complexities, the present study, based
      on the fundamental concept that genomic instability is the engine of both tumor
      progression and tumor heterogeneity, was conducted to test the hypothesis that
      breast cancer pathogenesis is driven by double-strand break (DSB)-initiated
      chromosome instability (CIN). The rationale underlying this hypothesis is derived
      from the clues provided by family breast cancer syndromes, in which
      susceptibility genes, including p53, ATM, BRCA1 and BRCA2, are involved within
      the common functional pathway of DSB-related checkpoint/ repair. Because genomic
      deletion caused by DSB is reflected in the genetic mechanism of loss of
      heterozygosity (LOH), this genome-wide LOH study was conducted, using 100 tumors
      and 400 microsatellite markers. To minimize the effect of heterogeneity within
      tumors, the experimental technique of laser capture microdissection was used to
      ensure that genetic and phenotypic examinations were based on the same tumor
      cells. Support for our hypothesis comes from the observations that: (a) the
      extent of DSB-initiated CIN in tumors significantly increased as tumors
      progressed to poorer grades or later stages; (b) in the sequential steps toward
      CIN, the loci of p53 and ATM, the key checkpoint genes against DSB, were lost at
      the earliest stage; and (c) many loci identified to be important in breast
      tumorigenesis were the genomic sites possibly harboring the genes involved in DSB
      related checkpoint/repair (including RAD51, RAD52, and BRCA1) or CIN (including
      FA-A, FA-D, and WRN), and a higher number of these loci showing LOH was
      significantly associated with increased level of DSB-initiated CIN (P < 0.0001).
      Breast cancers are thus considered to be sequentially progressive with CIN.
      However, CIN might also cause genetic heterogeneity, which was revealed by the
      findings that LOH at some markers was observed only in the component of ductal
      carcinoma in situ but not in the invasive component of the same tumors. In
      addition, some markers were found to preferentially lose at specific tumor
      grades, implying their contribution to genetic heterogeneity during tumor
      development. Therefore, this study suggests that breast cancer progression is
      clonal with regard to CIN, but different breast cancers would present distinct
      molecular profiles resulting from genetic heterogeneity caused by CIN.

PMID- 10919665
TI  - A case-control study confirms that microsatellite assay can identify patients at
      risk of developing oral squamous cell carcinoma within a field of cancerization.
AB  - Distinguishing true precursor lesions on the basis of clinical or histological
      features alone is unreliable but is important so that appropriate intervention
      can be instigated. Preliminary studies have shown that a microsatellite assay may
      provide important new prognostic information. To build on these observations, we
      have performed a case-control study to establish whether we can be confident
      about incorporating this new information into clinical practice. We have
      determined the frequency of allelic imbalance (AI) within key chromosomal
      regions, by matching 39 cases with dysplastic oral lesions that developed a tumor
      on the same side of the mouth, for as many variables as possible, with controls
      presenting with similar lesions that did not progress to malignancy when followed
      for the same period. Our findings confirm that the group that developed tumor had
      precursor lesions that harbor AI at more loci (P = 0.002). However, no consistent
      patterns of AI were associated with the three grades of dysplasia: mild,
      moderate, and severe. One-third of the tumors developed at the same site as the
      dysplastic lesion and two-thirds at a different site, which revealed that the
      presence of these aberrations in a dysplastic lesion provided information about
      the risk of malignant change within a larger field. This suggests that the
      process of field cancerization is more widespread than previously recognized. On
      the basis of these findings, we advocate complete excision of all suspicious
      areas that show AI at two or more key loci, regardless of the degree of
      dysplasia. However, because the remaining mucosa is also "at risk," these cases
      should also be targeted to receive dietary advice and chemoprevention, to
      minimize their risk of tumor formation at a distant site.

PMID- 10919666
TI  - DNA sequence copy number changes in gastrointestinal stromal tumors: tumor
      progression and prognostic significance.
AB  - To identify genetic changes related to tumor progression and find out diagnostic
      and prognostic genetic markers in gastrointestinal stromal tumors (GISTs), 95
      tumor samples (24 benign GISTs, 36 malignant primary GISTs, and 35 GIST
      metastases) from 60 patients were studied using comparative genomic
      hybridization. DNA copy number changes were detected in all samples. Benign GISTs
      had a mean of 2.6 aberrations/ sample (losses:gains, 5:1) and significantly fewer
      DNA copy number changes and fewer gains than malignant primary and metastatic
      GISTs (P < 0.01). High-level amplifications were not seen in benign GISTs.
      Malignant primary GISTs had a mean of 7.5 aberrations/tumor (losses: gains,
      1.6:1), whereas the mean number of aberrations/metastatic GIST was 9
      (losses:gains, 1.8:1). Frequent changes observed in all GIST groups included
      losses in chromosome arms 1p (51%), 14q (74%), and 22q (53%). Gains and high
      level amplifications at 8q and 17q were significantly more frequent in metastatic
      GISTs (57 and 43%) than in benign GISTs (8 and 0%; P < 0.001) and malignant
      primary GISTs (33 and 25%; P < 0.05). Gains and high-level amplifications at 20q
      were only seen in malignant primary and metastatic GISTs (P < 0.01), and gains at
      5p were not detected in benign GISTs (P < 0.01). Losses in chromosome arm 9p were
      never seen in benign tumors (P < 0.001), and they were more frequent in
      metastatic GISTs than in malignant primary GISTs (63 and 36%; P < 0.05). Losses
      in 13q were less frequent in benign GISTs than in malignant primary (P < 0.05)
      and metastatic (P < 0.01) GISTs. Our results show that several DNA copy number
      changes are related to the behavior of GISTs and can be used as prognostic
      markers for tumor progression.

PMID- 10919667
TI  - Down-regulation of neu/HER-2 by interferon-gamma in prostate cancer cells.
AB  - Interferons (IFNs) are known to possess potent antitumor properties. Previous
      studies have indicated that IFNs are capable of modulating the expression of
      various tumor suppressor genes and oncogenes. In this study, we looked at the
      effect of IFN-gamma on the neu/HER-2 proto-oncogene in the DU145, LNCaP, and PC-3
      prostate cancer cell lines. IFN-gamma inhibited cell proliferation in both DU145
      and PC-3 cells in a dose-dependent manner, whereas no inhibition of proliferation
      was seen in LNCaP cells. Correspondingly, IFN-gamma treatment of DU145 and PC-3
      cells resulted in an increased production of the cyclin-dependent kinase
      inhibitor p21(WAF1), whereas no increase in p21(WAF1) was seen in LNCaP cells. In
      addition, IFN-gamma induced phosphorylation of signal transducer and activator of
      transcription (STAT) 1 in DU145 and PC-3 cells, but not in LNCaP cells.
      Consistent with these findings, we found that IFN-gamma treatment of DU145 and PC
      3 cells caused a reduction in neu/HER-2 expression, with no change seen in the
      LNCaP cell line. Transfection and overexpression of the transcriptional
      coactivator p300 in PC-3 cells suppressed the reduction in neu/HER-2 expression
      after IFN-gamma treatment, suggesting a role for p300 in neu/HER-2 expression.
      The antiproliferative activity and p21(WAF1) production of these cells after IFN
      gamma treatment were found to be reduced as well. We propose that the down
      regulation of neu/HER-2 by IFN-gamma occurs via the interaction of phosphorylated
      STAT1 with p300 because IFN-gamma activities requiring phosphorylated STAT1 are
      reduced in cells overexpressing p300. These findings suggest that neu/HER-2 may
      play a role in the growth of some prostate cancers and that IFN-gamma may
      suppress such cancers by down-regulation of neu/HER-2.

PMID- 10919668
TI  - Activation of insulin-like growth factor I receptor signaling pathway is critical
      for mouse plasma cell tumor growth.
AB  - Plasma cell neoplasia in humans generally occurs as multiple myeloma, an
      incurable form of cancer. Tumors with marked similarity can be induced in mice by
      a variety of agents, including chemicals, silicone, and oncogene-containing
      retroviruses, suggesting the use of murine tumors as an informative model to
      study plasma cell disease. Herein, we have focused on the role of insulin-like
      growth factor I receptor (IGF-IR) signaling in the development of plasma cell
      disease. The insulin receptor substrate 2/phosphatidylinositol 3'-kinase/p70S6K
      pathway was found to be either constitutively or IGF-I-dependently activated in
      all plasma cell tumors. Biological relevance was demonstrated in that plasma cell
      lines with up-regulated IGF-IR expression levels exhibited mitogenic responses to
      IGF-I. More importantly, expression of a dominant-negative mutant of IGF-IR in
      these lines strongly suppressed tumorigenesis in vivo. Taken together, these
      results demonstrate that up-regulation and activation of IGF-IR and the
      downstream signaling pathway involving insulin receptor substrate 2,
      phosphatidylinositol 3'-kinase, and p70S6K may play an important role in the
      development of a broad spectrum of plasma cell tumors.

PMID- 10919669
TI  - Akt/protein kinase B promotes survival and hormone-independent proliferation of
      thyroid cells in the absence of dedifferentiating and transforming effects.
AB  - The Akt/protein kinase B serine/threonine kinase is a downstream effector of
      phosphoinositide 3-kinase (PI3K). Akt is an important component of mitogenic and
      antiapoptotic signaling pathways and is implicated in neoplastic transformation.
      Thyroid cells in culture retain a differentiated phenotype consisting of
      epithelial cell morphology and the expression of several tissue-specific genes.
      The survival and proliferation of these cells depend on thyrotropin and a mixture
      of five additional hormones that includes insulin. The regulation of
      proliferation and the expression of the thyroid differentiation program are
      intimately connected processes. As a result, oncogenes that induce hormone
      independent proliferation invariably impair the expression of the thyroid
      specific differentiation markers. Given that thyrotropin and insulin stimulate
      Akt activation in thyroid cells, we set out to determine the effects of Akt on
      thyroid cell proliferation, survival, and differentiation. To this end, we
      expressed constitutively active myristylated Akt (myrAkt) in PC Cl 3 thyroid
      cells. The myrAkt-expressing cells continued to proliferate, even in the absence
      of hormones, and they were resistant to programmed cell death induced by
      starvation. These effects were paralleled by the induction of the G1 cyclins D3
      and E and by the inhibition of induction of the proapoptotic Fas, Fas ligand, and
      BAD genes in starved cells. However, in marked contrast with several other
      oncogenes, myrAkt did not interfere with the expression of thyroid
      differentiation functions. These results unveil the existence of an Akt-triggered
      thyroid cell pathway that modulates proliferation and survival without affecting
      the expression of the thyroid cell differentiated phenotype.

PMID- 10919670
TI  - Histone H3 and heat shock protein GRP78 are selectively cross-linked to DNA by
      photoactivated gilvocarcin V in human fibroblasts.
AB  - Gilvocarcin V (GV) is an antitumor antibiotic with a coumarin-based aromatic
      structure that promotes protein-DNA cross-linking when photoactivated by near-UV
      light. We have now identified several proteins that are selectively cross-linked
      to DNA in human fibroblasts by photoactivated GV, using NH2-terminal amino acid
      sequencing and Western blot analysis of the purified cross-linked proteins. The
      selectively cross-linked proteins are histone H3 and GRP78, a heat shock protein
      belonging to the heat shock protein-70 family. The hydrophobic leader sequence is
      missing from the cross-linked GRP78, suggesting that only the processed form of
      the protein is cross-linked to DNA. It is primarily the phosphorylated form of
      histone H3 that is cross-linked to DNA. Gel retardation analysis from four
      different GV-treated human fibroblast cell lines revealed two distinct shifted
      bands, and subsequent immunoblotting confirmed in situ that the slower and the
      faster bands, respectively, contained GRP78 and histone H3 cross-linked to DNA.
      The selective cross-linking of these particular proteins is dependent on UV
      irradiation in the presence of GV, which may help to clarify the unique molecular
      mechanism of this potent antitumor agent.

PMID- 10919671
TI  - The role of cellular glutathione peroxidase redox regulation in the suppression
      of tumor cell growth by manganese superoxide dismutase.
AB  - Manganese-containing superoxide dismutase (MnSOD) is an essential primary
      antioxidant enzyme that converts superoxide radical to hydrogen peroxide and
      molecular oxygen within the mitochondrial matrix. Cytosolic glutathione
      peroxidase (GPX) converts hydrogen peroxide into water. MnSOD is reduced in a
      variety of tumor types and has been proposed to be a new kind of tumor suppressor
      gene, but the mechanism(s) by which MnSOD suppresses malignancy is unclear.
      According to the enzymatic reactions catalyzed by MnSOD and cytosolic GPX, change
      in the cellular redox status, especially change attributable to accumulation of
      hydrogen peroxide or other hydroperoxides, is a possible reason to explain the
      suppression of tumor growth observed in MnSOD-overexpressing cells. To test this
      possible mechanism, we transfected human cytosolic GPX cDNA into human glioma
      cells overexpressing MnSOD. The results showed that GPX overexpression not only
      reversed the tumor cell growth inhibition caused by MnSOD overexpression but also
      altered the cellular contents of total glutathione, reduced glutathione, oxidized
      glutathione, and intracellular reactive oxygen species. Overexpression of GPX
      also inhibited degradation of the inhibitory subunit alpha of nuclear factor-KB.
      These results suggest that hydrogen peroxide or other hydroperoxides appear to be
      key reactants in the tumor suppression by MnSOD overexpression, and growth
      inhibition correlates with the intracellular redox status. This work suggests
      that manipulations that inhibit peroxide removal should enhance the tumor
      suppressive effect of MnSOD overexpression.

PMID- 10919673
TI  - Metabolic inhibitors sensitize for CD95 (APO-1/Fas)-induced apoptosis by down
      regulating Fas-associated death domain-like interleukin 1-converting enzyme
      inhibitory protein expression.
AB  - Protein or RNA synthesis inhibitors are known to sensitize some resistant cells
      for death receptor-induced apoptosis. However, the molecular mechanism(s)
      involved in sensitization have not yet been defined exactly. Here, we report that
      metabolic inhibitors such as cycloheximide (CHX) or actinomycin D (ActD)
      sensitize for CD95-induced apoptosis by strongly down-regulating FLIP and RIP
      expression. Metabolic labeling studies revealed that CHX or ActD inhibited
      protein or RNA synthesis at concentrations required for sensitization. In
      contrast to Fas-associated death domain (FADD) or caspase-8, FADD-like
      interleukin 1-converting enzyme-inhibitory protein (FLIP) and RIP protein levels
      rapidly decreased upon treatment with CHX or ActD, indicating that both molecules
      have a high turnover rate. Selective down-regulation of FLIP expression by FLIP
      antisense oligonucleotides sensitized for CD95-induced apoptosis. Reduction of
      FLIP levels resulted in undetectable amounts of FLIP at the CD95 death-inducing
      signaling complex (DISC) upon CD95 stimulation, thereby enhancing the recruitment
      of caspase-8 to the DISC and caspase-8 activation. CHX- or ActD-mediated
      sensitization to CD95-induced apoptosis was predominantly found in type I cells
      in which FADD and caspase-8 are recruited to CD95 upon stimulation but not in
      type II cells in which no DISC formation is detected. Pretreatment with CHX or
      ActD sensitized for subsequent CD95 stimulation compared with cells without
      pretreatment. CHX or ActD also reduced XIAP expression and similarly sensitized
      for tumor necrosis factor-related apoptosis-inducing ligand- or tumor necrosis
      factor-alpha-induced apoptosis. Because blockade of death receptor triggering by
      FLIP overexpression has recently been implicated in tumorigenesis and treatment
      resistance in vivo, strategies to inhibit FLIP expression, e.g., by metabolic
      inhibitors, may prove to be a useful complementary tool for the treatment of
      cancer.

PMID- 10919672
TI  - Inhibition of Hsp90 function by ansamycins causes retinoblastoma gene product
      dependent G1 arrest.
AB  - The ansamycin antibiotics, herbimycin A (HA) and geldanamycin (GM), bind to a
      conserved pocket in heat shock protein 90 (Hsp90) and alter the function of this
      chaperone protein. Occupancy of this pocket results in the degradation of a
      subset of signaling molecules. These include proteins known to associate with
      Hsp90, e.g., the steroid receptors and Raf, as well as certain transmembrane
      tyrosine kinases, such as the ErbB receptor family. In a variety of tumor cell
      lines, treatment with HA potently inhibited cellular proliferation by inducing G1
      arrest. This arrest was accompanied by hypophosphorylation of the retinoblastoma
      gene product (RB) and rapid down-regulation of cyclin D- and E-associated kinase
      activities. Inhibition of kinase activity was found to result from loss in
      expression of cyclins D1, D3, and E, as well as the associated cyclin-dependent
      kinases, cyclin-dependent kinase 4 and cyclin-dependent kinase 6. In addition, HA
      treatment also caused a late induction of p27(Kip1) protein. The loss of cyclin D
      preceded the other effects of HA, suggesting that it might be the primary cause
      of G1 arrest. To determine whether the effects of HA are mediated by selective
      inhibition of the cyclin D-RB pathway, HA was added to tumor cell lines lacking
      functional RB. HA treatment of Rb-negative tumor cell lines failed to elicit a G1
      arrest. In addition, after release from synchronization with nocodazole, Rb
      negative but not Rb-positive cell lines were able to progress through G1 into S
      phase in the presence of HA. Together, these findings suggest that induction of
      G1 arrest by HA results from down-regulation of cyclin D expression and its
      associated kinase activity. Furthermore, these findings imply that Hsp90
      selectively regulates signaling pathways upstream of RB.

PMID- 10919674
TI  - E1A overcomes the apoptosis block in BCR-ABL+ leukemia cells and renders cells
      susceptible to induction of apoptosis by chemotherapeutic agents.
AB  - A crucial function of the BCR-ABL chimeric gene in chronic myeloid leukemia is
      the prolongation of cell survival by inhibition of apoptosis. BCR-ABL expression
      confers cross-resistance to multiple genotoxic anticancer drugs by inhibition of
      the apoptotic response to DNA damage in association with cell cycle arrest at the
      G2-M restriction point. Previous reports indicated that BCR-ABL exerts its
      antiapoptotic effect against various apoptotic stimuli upstream to the cleavage
      and activity of caspase-3. Here we show that the adenovirus E1A protein induces
      substantial apoptosis in BCR-ABL expressing K562 and LAMA-84 leukemia cells. This
      apoptotic activity of E1A is accompanied by processing of caspase-3 and cleavage
      of poly(ADP-ribose) polymerase and can be significantly blocked by z-VAD-fmk Z
      Val-Ala-Asp(OCH3)-CH2F and the caspase-3-specific inhibitor Z-DEVD-FMK Z
      Asp(OCH3)-Glu-Val-Asp(OCH3)-CH2F. Moreover, E1A renders K562 cells, which are
      particularly resistant to cell death irrespective of the inducing agent,
      susceptible to induction of apoptosis by the chemotherapeutic agents etoposide
      and daunorubicin. Counteracting the DNA damage-induced inactivation of cdc2
      kinase, E1A reverses the drug-induced G2-M arrest These results indicate that
      solitary delivery of E1A significantly antagonizes BCR-ABL-induced antiapoptotic
      functions and circumvents the inherent resistance to DNA damage-induced
      apoptosis, supporting the use of E1A in combination with chemotherapeutic agents
      as a promising therapeutic strategy for successful treatment of Philadelphia
      chromosome-positive leukemia in vivo.

PMID- 10919675
TI  - Dnmt1N/+ reduces the net growth rate and multiplicity of intestinal adenomas in
      C57BL/6-multiple intestinal neoplasia (Min)/+ mice independently of p53 but
      demonstrates strong synergy with the modifier of Min 1(AKR) resistance allele.
AB  - Altered patterns of the 5-cytosine methylation of genomic DNA are associated with
      the development of a wide range of human cancers. We have studied the mechanisms
      and genetic pathways by which a targeted heterozygous deficiency in the murine 5
      cytosine DNA methyltransferase gene (Dnmt1(N/+)) diminishes intestinal
      tumorigenesis in C57BL/6-multiple intestinal neoplasia (Min)/+ mice. We found
      that Dnmt1(N/+) retards the net growth rate of intestinal adenomas and reduces
      tumor multiplicity by approximately 50%. This tumor resistance affects the entire
      intestinal tract and is independent of the status of modifier of Min 1 and p53,
      two loci that have been found to confer strong resistance to Min-induced
      neoplasia Interestingly, Dnmt/(N/+) and modifier of Min 1 resistance interact
      synergistically, together virtually eliminating tumor incidence. This finding may
      provide an insight into potential combinatorial therapeutic approaches for
      treating human colon cancer.

PMID- 10919676
TI  - STAT5 activation is required for interleukin-9-dependent growth and
      transformation of lymphoid cells.
AB  - Interleukin-9 (IL-9) is a growth factor for T cells and various hematopoietic and
      lymphoid tumor cells. IL-9 signaling involves activation of Janus kinase (JAK)1
      and JAK3 kinases, and signal transducer and activator of transcription (STAT)1,
      STAT3 and STAT5. Using a dominant negative form of STAT5 (STAT5delta), we
      demonstrated that this factor is an important mediator of IL-9-dependent Ba/F3
      cell growth. Mutation of the STAT binding site of the IL-9 receptor (tyr116phe)
      results in an important decrease in STAT activation and inhibition of
      proliferation in the presence of IL-9. A small number of cells escape this
      inhibition, and IL-9-dependent cell lines could be derived. The selected cells
      required activation of STAT5 for growth, which was blocked by STAT5delta
      expression and enhanced by overexpression of wild-type STAT5. In contrast to
      parental cells, Ba/F3-Phe116 cells growing in the presence of IL-9 further
      progress to cytokine-independent tumorigenic clones. These tumorigenic clones
      exhibited a strong cytokine-independent activation of JAK1 and STAT5, which most
      likely supports their proliferation. Transfection of a constitutively activated
      variant of STAT5 promoted the growth of wild-type Ba/F3 cells in the absence of
      cytokine. Finally, the expression of the proto-oncogene pim-1 was correlated with
      STAT5 activation and cell growth. Our data suggest that STAT5 is an important
      mediator of IL-9-driven proliferation and that dysregulation of STAT5 activation
      favors tumorigenesis of lymphoid cells.

PMID- 10919677
TI  - Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents
      metastasis by blocking E-selectin expression.
AB  - Although the beneficial effect of cimetidine on survival in cancer has been
      clinically demonstrated in colorectal cancer patients, the mode of action of
      cimetidine has not been elucidated. In this report, we have demonstrated for the
      first time that cimetidine can block the adhesion of a colorectal tumor cell line
      to the endothelial cell monolayer in cell culture and that it can suppress the
      metastasis of the tumor cell in a nude mouse model. We also demonstrated that
      these antimetastasis effects of cimetidine might occur through down-regulation of
      the cell surface expression of E-selectin on endothelial cells, a ligand for
      sialyl Lewis antigens on tumor cells. We found that the cimetidine-mediated down
      regulation of E-selectin did not involve down-regulation of E-selectin mRNA or
      blocking of the nuclear translocation of nuclear factor kappaB, a transcriptional
      activator of E-selectin gene expression. Because two other histamine type 2
      receptor antagonists, famotidine and ranitidine, did not show any similar effect,
      these actions of cimetidine probably do not occur via blocking of the histamine
      receptor. These observations support the idea that cancer metastasis can be
      blocked by cimetidine administration through blocking the adhesion of tumor cells
      to the endothelium when an interaction between E-selectin and sialyl-Lewis
      antigens plays a role.

PMID- 10919678
TI  - The pressurized metered dose inhaler (pMDI) remains the most commonly prescribed
      device for the delivery of inhaled asthma medications.

PMID- 10919679
TI  - Pharmaceutical transition to non-CFC pressurized metered dose inhalers.
AB  - The production of ozone-depleting chlorofluorocarbons (CFCs) was discontinued on
      1 January 1996 for all uses deemed non-essential under the Montreal Protocol.
      However, the use of CFCs as propellants in pressurized metered dose inhalers
      (pMDIs) was classed as essential, providing an exemption from the agreement.
      Following extensive research, the hydrofluoroalkanes (HFA) 134a and 227 were
      identified as the only suitable replacements for CFC propellants in pMDIs. The
      drug delivery of pMDIs formulated with HFA 134a as a propellant and containing
      either salbutamol (100 microg per actuation) or fluticasone propionate (125 and
      250 microg per actuation) have been assessed for dose uniformity and particle
      size distribution. All of the HFA 134a pMDIs delivered doses throughout the life
      of the canisters that were reproducible and within specified regulatory
      requirements. Each of the products provided an emitted dose which was within +/-
      25% of the mean value indicating accurate and consistent dosing (93, 112 and 221
      microg per metered dose for the salbutamol 100 microg and fluticasone propionate
      125 and 250 microg HFA 134a pMDIs, respectively). These findings were unaffected
      by changing the storage orientation of the pMDI or by using the device in a
      manner designed to simulate typical patient use. The particle size distributions
      of HFA 134a pMDI doses did not differ significantly from those of the
      corresponding CFC pMDIs. As a result of the similar pharmaceutical performance,
      it is unnecessary to change the label claim dose of active drug when making the
      transition from a CFC to an HFA 134a pMDI for salbutamol (Ventolin) and
      fluticasone propionate (Flixotide). A seamless transition to non-CFC pMDIs will
      help to maintain the confidence of patients and healthcare professionals in
      asthma therapy.

PMID- 10919680
TI  - From hydrofluoroalkane pressurized metered dose inhalers (pMDIs) and
      comparability with chlorofluorocarbon pMDIs.
AB  - Fluticasone propionate pressurized metered dose inhalers (pMDIs) containing the
      hydrofluoroalkane (HFA) propellant, HFA 134a, are being developed to replace
      existing chlorofluorocarbon (CFC) pMDIs. This is part of the ongoing worldwide
      project to limit the damage to the earth's ozone layer. The in vivo performance
      and dose proportionality of fluticasone propionate HFA 134a pMDIs was examined
      for fluticasone propionate doses of 400, 1000 and 2000 microg using the 50, 125
      and 250 microg strength pMDIs, respectively. The 125 and 250 microg strength HFA
      134a pMDIs were compared with corresponding fluticasone propionate CFC pMDIs.
      Twenty-three healthy subjects participated in this single dose, randomized, five
      way, cross-over study. Serial blood samples were collected 24 h post-dose to
      measure fluticasone propionate plasma concentrations. Twenty-four hour urinary
      free cortisol was also measured before and after dosing. A dose-proportional
      increase in plasma fluticasone propionate concentrations was observed with
      increasing dose for the HFA 134a pMDIs. This was associated with a dose-related
      decrease in urinary cortisol excretion. Similar or lower fluticasone propionate
      systemic exposure was observed with the HFA 134a pMDIs compared to the
      corresponding CFC inhalers. The differences in systemic exposure observed for the
      HFA 134a and CFC pMDIs were too small to produce a differential effect on urinary
      cortisol excretion. Since fluticasone propionate has negligible oral
      bioavailability, the systemic exposure, which arises only from pulmonary
      absorption, is a measure of lung deposition. There was a good correlation between
      the in vitro fine particle mass produced by the different strengths and types of
      pMDI and the systemic exposure to fluticasone propionate. Therefore, the
      fluticasone propionate HFA 134a pMDI is an acceptable pharmaceutical alternative
      to the current CFC pMDI, producing similar lung deposition and no increase in
      systemic exposure at microgram equivalent doses.

PMID- 10919681
TI  - Equivalence of as-required salbutamol propelled by propellants 11 and 12 or HFA
      134a in mild to moderate asthmatics. German Study Group.
AB  - This randomized, double-blind, parallel-group study compared the efficacy and
      tolerability of as-required salbutamol 100 microg administered from either a
      chlorofluorocarbon (CFC) pressurized metered dose inhaler (pMDI; Ventolin) or
      from a non-CFC hydrofluoroalkane (HFA) 134a pMDI (Ventolin CFC-free) in patients
      with mild to moderate asthma. All patients (n = 423) continued with their
      standard asthma therapy, and recorded their daily use of study medication,
      morning and evening peak expiratory flow (PEF) and symptom scores, throughout the
      4-week treatment period. Clinic lung function was measured at 2-week intervals.
      The median daily use of inhaled study medication remained constant at four
      actuations per day throughout the study in both treatment groups and statistical
      analysis indicated that the two formulations were equivalent. Small improvements
      in both treatment groups were reported in mean morning and evening PEF, clinic
      forced expiratory volume in 1 sec and clinic PEF and there were no significant
      differences between the two groups. Both formulations were well tolerated. This
      study indicates that as-required salbutamol 100 microg administered via a HFA
      134a pMDI is as effective and safe as the currently available CFC-propelled
      formulation.

PMID- 10919682
TI  - Equivalence of salbutamol 200 microg four times daily propelled by propellants 11
      and 12 or HFA 134a in mild to moderate asthmatics. Eastern European study group.
AB  - The phasing out of chlorofluorocarbons (CFCs) requires the development of an
      alternative non-ozone depleting propellant for use in pressurized metered dose
      inhalers (pMDIs). The present study assessed the effects on tolerability and
      efficacy of a switch from the currently available formulation containing the CFC
      propellants 11 and 12 to an alternative non-CFC formulation using the propellant
      hydrofluoroalkane (HFA) 134a in patients with mild to moderate asthma. After a 4
      week run-in period during which patients received salbutamol 200 microg four
      times daily from a CFC pMDI, 547 patients were randomized to 12 weeks of
      treatment with salbutamol 200 microg four times daily administered from either an
      HFA 134a pMDI (Ventolin CFC-free; 277 patients) or CFC pMDI (Ventolin, 270
      patients). At the end of this period, all patients then received a further 4
      weeks of treatment with the same dose of salbutamol via a CFC pMDI (run-out
      period). On the basis that high doses of beta2-agonists are known to increase
      heart rate, change in heart rate was selected as the primary outcome variable.
      Small increases in heart rate were observed during the treatment period and these
      changes were comparable in both groups; the 90% confidence interval for the
      treatment differences was within the predefined limits for clinical equivalence
      (+/- 10 beats min(-1)). The incidence of adverse events was similar in both
      groups and there were no reports of paradoxical bronchospasm. Furthermore, daily
      PEF measurements showed comparability in terms of lung function. Symptom scores
      and use of additional bronchodilator were also similar in both groups. These
      results demonstrate that salbutamol (800 microg day(-1)), formulated with HFA
      134a is equivalent to the current CFC formulation in terms of tolerability and
      efficacy.

PMID- 10919683
TI  - Clinical efficacy and safety of fluticasone propionate 250 microg twice daily
      administered via a HFA 134a pressurized metered dose inhaler to patients with
      mild to moderate asthma. French study group.
AB  - This study compared the efficacy and safety of the fluticasone propionate 125
      microg pressurized metered dose inhaler (pMDI) propelled by either
      hydrofluoroalkane (HFA) 134a or chlorofluorocarbon (CFC) propellants, in adult
      patients with asthma. HFA 134a is a non-ozone depleting propellant used as a
      replacement for the CFC propellants 11 and 12 which are being phased out in
      accordance with the Montreal Protocol. Three hundred and eighty patients with
      mild to moderate asthma and 'room for improvement' in their treatment were
      randomized to receive fluticasone propionate 250 microg twice daily via pMDIs
      propelled by either CFC propellants 11 and 12 (n = 195) or HFA 134a (n = 185).
      Fluticasone propionate significantly improved lung function over the 4-week
      treatment period in both treatment groups. The improvement in mean morning peak
      expiratory flow (PEF) after 7 days of treatment was approximately 12 l min(-1) in
      both groups, rising to approximately 22 l min(-1) at the end of the 4-week
      treatment period. The adjusted mean difference between the two formulations over
      weeks 1-4 was -1 l min(-1) (90% confidence interval: -7, 5 l min(-1)), confirming
      their equivalence. Clinical comparability was also demonstrated with respect to
      secondary efficacy variables, including daily symptom scores, evening PEF and
      clinic visit expiratory measurements. There were no clinically relevant
      differences in adverse events or serum cortisol levels between the two groups.
      The fluticasone propionate 125 microg HFA 134a pMDI is an effective and well
      tolerated product and is a suitable replacement for the fluticasone propionate
      125 microg CFC pMDI at a microgram equivalent dose.

PMID- 10919684
TI  - Clinical efficacy and safety of fluticasone propionate 1 mg per day administered
      via a HFA 134a pressurized metered dose inhaler to patients with moderate to
      severe asthma. International study group.
AB  - This multi-national, double-blind, randomized, parallel-group study compared the
      efficacy and tolerability of fluticasone propionate 500 microg twice daily
      propelled either by the non-chlorofluorocarbon (CFC) propellant,
      hydrofluoroalkane (HFA) 134a, or the CFC propellants 11 and 12 used in the
      established pressurized metered dose inhaler (pMDI). The study period was 12
      months and involved 412 subjects with moderate to severe asthma (HFA 134a pMDI: n
      = 203; CFC pMDI: n = 209). For the first 3 months, subjects kept a daily record
      card and attended the clinic every 4 weeks. Thereafter, they kept daily diaries
      for 2 weeks before each clinic assessment, which were performed at the end of 6,
      9 and 12 months. Mean morning peak expiratory flow (PEF) increased during the
      first week in both treatment groups. By the end of week 12 the adjusted mean
      increase from baseline in morning PEF was 21 and 23 l min(-1) in the HFA 134a and
      CFC pMDI groups, respectively, and this increase was maintained throughout the 12
      month study period. Similar improvements were detected in other diary card
      parameters and in clinic lung function measurements. The two groups were shown to
      be clinically equivalent in terms of all efficacy variables and there were no
      differences in tolerability. There were few reports of low serum cortisol levels
      during the 12-month study period, and serum cortisol levels were similar at
      baseline and after 12 weeks and 12 months of treatment in the two groups. In
      conclusion, the new HFA 134a fluticasone propionate pMDI is as effective and safe
      as the established CFC fluticasone propionate pMDI when used at a dosage of 1 mg
      day(-1).

PMID- 10919685
TI  - Clinical efficacy and safety of fluticasone propionate 1 mg twice daily
      administered via a HFA 134a pressurized metered dose inhaler to patients with
      severe asthma. U.K. study group.
AB  - A randomized, double-blind, cross-over study was conducted to assess the efficacy
      and safety of fluticasone propionate 1 mg twice daily administered via a
      pressurized metered dose inhaler (pMDI) containing the new non-chlorofluorocarbon
      (CFC) propellant (HFA 134a), or the established CFC propellants 11 and 12 in
      patients with severe asthma. The study comprised a 2-week run-in period followed
      by two 6-week treatment periods, with no washout period in between. One hundred
      and nineteen symptomatic adult patients with severe asthma, who were receiving
      inhaled beclomethasone 2-4 mg day(-1) or equivalent, were randomized to
      treatment. Patients were randomized to one of two sequence groups (sequence 1:
      HFA 134a pMDI then CFC pMDI or sequence 2: CFC pMDI then HFA 134a pMDI). The
      sequence groups differed with respect to mean peak expiratory flow (PEF) at
      baseline; however, the magnitude of the increase in PEF from baseline during
      treatment was similar in the two sequence groups. Mean PEF at baseline was 334 l
      min(-1) in sequence group 1 (HFA 134a-->CFC pMDI) and this increased to 357 l
      min(-1) and 366 l min(-1) during treatment with the HFA 134a and CFC pMDI,
      respectively. In sequence group 2 (CFC-->HFA 134a pMDI) mean PEF at baseline was
      297 l min(-1) and this increased to 336 l min(-1) and 328 l min(-1) during
      treatment with the HFA 134a and CFC pMDI, respectively. Based on an overall
      analysis of the two treatment groups at week 6, equivalence was demonstrated; the
      mean treatment difference (HFA 134a-CFC pMDI) in morning PEF was 0 l min(-1) (90%
      confidence interval (CI), for difference between groups: -7, 6 l min(-1)). There
      was a comparable improvement in secondary efficacy variables, including clinic
      lung function measurements, in the two treatment groups. The incidence and type
      of most adverse events were similar in the two treatment groups. There was no
      difference in the adjusted geometric mean morning serum cortisol levels after
      treatment with the HFA 134a and CFC pMDI. Therefore, the fluticasone propionate
      HFA 134a pMDI constitutes a suitable replacement for the established CFC pMDI at
      a microgram equivalent dose.

PMID- 10919686
TI  - Surface plasmon resonance analysis of dynamic biological interactions with
      biomaterials.
AB  - Surface plasmon resonance (SPR) is an optical technique that is widely gaining
      recognition as a valuable tool to investigate biological interactions. SPR offers
      real time in situ analysis of dynamic surface events and, thus, is capable of
      defining rates of adsorption and desorption for a range of surface interactions.
      In this review we highlight the diversity of SPR analysis. Examples of a wide
      range of applications of SPR are presented, concentrating on work relevant to the
      analysis of biomaterials. Particular emphasis is given to the use of SPR as a
      complimentary tool, showing the broad range of techniques that are routinely used
      alongside SPR analysis.

PMID- 10919687
TI  - In vitro and in vivo degradation of porous poly(DL-lactic-co-glycolic acid)
      foams.
AB  - This study investigated the in vitro degradation of porous poly(DL-lactic-co
      glycolic acid) (PLGA) foams during a 20-week period in pH 7.4 phosphate-buffered
      saline (PBS) at 37 degrees C and their in vivo degradation following implantation
      in rat mesentery for up to 8 weeks. Three types of PLGA 85 : 15 and three types
      of 50 : 50 foams were fabricated using a solvent-casting, particulate-leaching
      technique. The two types had initial salt weight fraction of 80 and 90%, and a
      salt particle size of 106-150 microm, while the third type had 90% initial weight
      fraction of salt in the size range 0-53 microm. The porosities of the resulting
      foams were 0.82, 0.89, and 0.85 for PLGA 85 : 15, and 0.73, 0.87, and 0.84 for
      PLGA 50 : 50 foams, respectively. The corresponding median pore diameters were
      30, 50, and 17 microm for PLGA 85: 15, and 19, 17, and 17 microm for PLGA 50 :
      50. The in vitro and in vivo degradation kinetics of PLGA 85: 15 foams were
      independent of pore morphology with insignificant variation in foam weight,
      thickness, pore distribution, compressive creep behavior, and morphology during
      degradation. The in vitro foam half-lives based on the weight average molecular
      weight were 11.1 +/- 1.8 (80%, 106-150 microm), 12.0 +/- 2.0 (90%, 106-150
      microm), and 11.6 +/- 1.3 (90%, 0-53 microm) weeks, similar to the corresponding
      values of 9.4 +/- 2.2, 14.3 +/- 1.5, and 13.7 +/- 3.3 weeks for in vivo
      degradation. In contrast, all PLGA 50 : 50 foams exhibited significant change in
      foam weight, water absorption, and pore distribution after 6-8 weeks of
      incubation with PBS. The in vitro foam half-lives were 3.3 +/- 0.3 (80%, 106-150
      microm), 3.0 +/- 0.3 (90%, 106-150 microm), and 3.2 +/- 0.1 (90%, 0-53 microm)
      weeks, and the corresponding in vivo half-lives were 1.9 micro 0.1, 2.2 +/- 0.2,
      and 2.4 +/- 0.2 weeks. The significantly shorter half-lives of PLGA 50: 50
      compared to 85: 15 foams indicated their faster degradation both in vitro and in
      vivo. In addition, PLGA 50: 50 foams exhibited significantly faster degradation
      in vivo as compared to in vitro conditions due to an autocatalytic effect of the
      accumulated acidic degradation products in the medium surrounding the implants.
      These results suggest that the polymer composition and environmental conditions
      have significant effects on the degradation rate of porous PLGA foams.

PMID- 10919688
TI  - Synthesis and characterisation of phosphorylcholine-based polymers useful for
      coating blood filtration devices.
AB  - Copolymers of 2-methacryloyloxyethylphosphorylcholine (MPC) and lauryl
      methacrylate (LMA) of molar ratios MPC: LMAX where x = 1, 2 or 4, have been
      synthesised by two different free-radical polymerisation techniques. The
      solubility characteristics of the resulting materials were investigated in a
      variety of water: alcohol solvent mixtures and found to be influenced not only by
      the molar ratio of MPC: LMA, but also the method of synthesis. A window of
      solubility was observed for certain copolymers and the alcohol used in the
      solvent mixture was also found to have a profound influence on the solubility
      profile of the polymers. These materials were soluble in a wider range of aqueous
      methanol mixtures compared to aqueous mixtures of higher aliphatic alcohols, such
      as ethanol or isopropyl alcohol, which was rationalised in terms of the affinity
      of the phosphorylcholine headgroup for the various alcohols relative to water. 1H
      nuclear magnetic resonance spectroscopy was used to further examine the solution
      properties of the copolymers in various solvents. The copolymer MPC: LMA2 was
      coated onto a variety of substrates from both alcohol-only and water: alcohol
      solvent systems and the surface properties of the films compared by static and
      dynamic contact angle, atomic force microscopy (AFM) and attenuated internal
      reflectance Fourier transform infrared spectroscopy (ATR-IR). The coating formed
      from the water: alcohol solvent was found to be hydrophilic in nature, possessing
      spontaneous wettability, whereas films formed from alcohol-only solvents were
      hydrophobic, and only on conditioning with water were more wettable surfaces
      attained. This phenomenon was applied in the coating of leukocyte filtration
      material, where the aqueous-based systems demonstrated lower critical wetting
      surface tension (CWST) and shorter wetting times relative to both uncoated
      filters and those coated from alcohol-only systems. The haemocompatibility of the
      coated filters was equivalent for both coating solvent systems. employed, and far
      superior when compared to the uncoated control.

PMID- 10919689
TI  - Behavior in simulated body fluid of calcium phosphate coatings obtained by laser
      ablation.
AB  - Three types of calcium phosphate coatings onto titanium alloy substrates,
      deposited by the laser ablation technique, were immersed in a simulated body
      fluid in order to determine their behavior in conditions similar to the human
      blood plasma. Neither the hydroxyapatite coating nor the amorphous calcium
      phosphate coating do dissolve and the alpha-tricalcium phosphate phase of the
      coating of beta-tricalcium phosphate with minor alpha phase slightly dissolves.
      Precipitation of an apatitic phase is favored onto the hydroxyapatite coating and
      onto the coating of beta-tricalcium phosphate with minor alpha phase. Onto the
      titanium alloy substrate reference there is also precipitation but at larger
      induction times. However, onto the amorphous calcium phosphate coating no
      precipitate is formed.

PMID- 10919690
TI  - Contractile behavior of smooth muscle actin-containing osteoblasts in collagen
      GAG matrices in vitro: implant-related cell contraction.
AB  - The contraction of connective tissue cells may facilitate their production and
      maintenance of extracellular matrix architecture and can benefit healing through
      wound closure. However, aberrant cell contraction can result in pathological
      contracture. Implants may stimulate this process leading to contracture of the
      surrounding fibrous capsule. In the case of compliant porous matrices used for
      tissue engineering the cell contraction may cause the constriction of pores and
      the distortion of the implant. The objective of this study was to determine if
      osteoblasts expressed a specific muscle actin, alpha-smooth muscle actin (SMA),
      that could provide for their contraction. Immunohistochemistry revealed the
      presence of SMA in some cells in all of three human and three canine trabecular
      bone specimens. The majority of the cells of an osteoblastic cell line, MC3T3-E
      1, also expressed this actin isoform in two-dimensional culture and when seeded
      into a collagen-glycosaminoglycan (GAG) matrix. These SMA-containing cells were
      found to cause contraction of the collagen-GAG analog of extracellular matrix.
      These findings demonstrate that osteoblasts can display contractile behavior that
      might help to explain the mechanism by which they impart architecture to bone
      matrix, including that at implant interfaces. An understanding of this process
      could also guide the development of matrices for bone tissue engineering.

PMID- 10919691
TI  - Carriers for skin delivery of trihexyphenidyl HCl: ethosomes vs. liposomes.
AB  - The purpose of this work was to characterize a novel ethosomal carrier containing
      trihexyphenidyl HCl (THP) and to investigate the delivery of THP from ethosomes
      versus classic liposomes. THP-ethosomal systems were shown by electron microscopy
      to contain small, phospholipid vesicles. As the THP concentration was increased
      from 0 to 3%, the size of the vesicles decreased from 154 to 90 nm. This is most
      likely due to the surface activity of THP (critical micelle concentration of 5.9
      mg/ml), as measured in this work. In addition, the ethosome zeta potential value
      increased as a function of THP concentration, from -4.5 to +10.4 when the THP
      concentration was increased from 0 to 3%. In contrast, THP liposomes were much
      larger and their charge was not affected by THP. When compared with standard
      liposomes, ethosomes had a higher entrapment capacity and a greater ability to
      deliver entrapped fluorescent probe to the deeper layers of skin. The flux of THP
      through nude mouse skin from THP ethosomes (0.21 mg/cm2 h) was 87, 51 and 4.5
      times higher than from liposomes, phosphate buffer and hydroethanolic solution,
      respectively (p < 0.01). The quantity of THP remaining in the skin at the end of
      the 18-h experiment was statistically significantly greater from the ethosomal
      system than from liposomes or a control hydroethanolic solution. Our results
      indicate that the ethosomal THP system may be a promising candidate for
      transdermal delivery of THP.

PMID- 10919693
TI  - Analysis of a dimethacrylate copolymer (bis-GMA and TEGDMA) network by DSC and
      13C solution and solid-state NMR spectroscopy.
AB  - In this work the effect of dilution with TEGDMA on the kinetics of Bis-GMA
      polymerization and on the extent of polymerization or degree of conversion was
      studied using (a) DSC and (b) NMR. The systems with lower viscosity and lower Tg
      exhibited higher extent of polymerization. For Bis-GMA/TEGDMA mixtures the
      calculated Tg values were found to be higher than the experimental values
      suggesting that a dilution effect is predominant rather than intermolecular
      hydrogen bonding. Solid state NMR has been shown to be a convenient method for
      measuring the total amount of conversion in a mixed monomer system. The
      disappearance of the NMR solution spectrum was used to reveal overall
      polymerization kinetics.

PMID- 10919692
TI  - Association of fibroblast orientation around titanium in vitro with expression of
      a muscle actin.
AB  - The objective of this study was to investigate the association of cell
      orientation around a biomaterial with expression of a contractile actin isoform.
      Selected cytokines and a fungal metabolite known to alter the cytoskeleton were
      used to modulate the fibroblast orientation around titanium in vitro and the
      synthesis of a specific muscle actin in order to reveal an association between
      these processes. A novel culture system using a fibronectin-coated silicone
      surface was employed to evaluate the orientation of human gingival fibroblasts
      around titanium discs. Round glass cover slips, 25 mm in diameter, were coated
      with polydimethylsiloxane. During the heat-induced polymerization process, two
      commercially pure titanium discs, 5 mm in diameter, were placed on the silicone
      at a distance of approximately 0.5 mm apart. The rubbery consistency of the
      silicone stabilized the metal discs on the cover slip and eliminated the risk of
      developing a lip at the edge of the titanium sample. The cover slip was then
      heated to complete polymerization of the silicone and subsequently coated with
      fibronectin. One hundred thousand human gingival fibroblasts were plated onto
      each glass cover slip containing the titanium discs. The cells were treated with
      one of the following prior to seeding on the cover slips: transforming growth
      factor-beta1 (TGF-beta1), platelet-derived growth factor-BB (PDGF-BB), interferon
      gamma (IFN-gamma) for cytochalasin-D. Untreated cells served as controls. The
      orientation of the cells at the surface of the titanium discs was evaluated
      microscopically and the cell content of alpha-smooth muscle actin (SMA) was
      determined by Western blot analysis and immunohistochemistry. A notable finding
      was the high correlation between the percentage of cells oriented perpendicular
      to the titanium surface and SMA synthesis. TGF-beta1, IFN-gamma and cytochalasin
      D increased synthesis of SMA while PDGF-BB decreased it. The findings support the
      proposition that SMA-enabled cell contraction may play a role in the orientation
      of cells to a biomaterial surface.

PMID- 10919694
TI  - Structural insights of glass-reinforced hydroxyapatite composites by Rietveld
      refinement.
AB  - Phase transformations and interstitial and/or substitution of trace elements
      during the liquid-phase sintering process of P2O5-CaO-MgO glass-reinforced
      hydroxyapatite (GR-HA) composites were examined by X-ray diffraction and Rietveld
      analyses. Using the Rietveld method for structure refinement, changes in the
      lattice parameters of the two main phases of the composites, hydroxyapatite (HA)
      and beta-tricalcium phosphate (beta-TCP), as well as changes in several bond
      lengths and in the occupancy of the hydroxyl oxygen site in the HA phase
      structure were assessed. The glasses gave rise to formation of between
      approximately 45 and 50% of beta-TCP, with evidence for the Mg2+ enhancing the
      formation of beta-TCP. Between 1,300 and 1,350 degrees C, the beta-TCP inverts to
      alpha-TCP, without further decomposition of the residual HA. The glasses showed
      evidence for stabilisation of the hydroxyl group located in the hydroxyl
      channels. This is supported by measurements of the hydroxyl channel radius (Rc),
      the Ca2-OH bond length and the hydroxyl oxygen occupancy (Oocc). Results showed
      that the Mg2+ containing glasses induced the beta-TCP phase formation in the
      structure of GR-HA composites and retarded the beta-TCP into alpha-TCP
      transformation at higher temperatures. The chemical composition of the P2O5
      glasses also induces modifications in the lattice parameters of the
      crystallographic phases present in the microstructure of the composites. This
      suggests some substitution of Mg2 + -for-Ca2+ in the beta-TCP structure during
      the liquid-phase sintering process.

PMID- 10919695
TI  - Effect of media composition on long-term in vitro stability of barium alginate
      and polyacrylic acid multilayer microcapsules.
AB  - For a number of applications stability of microcapsules is a critical factor.
      Since the maintenance of polyelectrolyte complexes depends considerably on the
      ion composition we tested the physical properties of barium alginate capsules and
      searched for conditions to improve stability by a multilayer coating with
      polyethylenimine (PEI) and polyacrylic acid (PAA). Mechanical stability and
      diameters were determined in barium alginate capsules and compared with
      multilayer capsules. Multilayer coating resulted in smaller capsules than barium
      complexing alone. The difference was more pronounced when CaCl2 was used instead
      of NaCl during coating. Barium alginate capsules and application of CaCl2 during
      coating led to continuous pressure profiles, whereas NaCl resulted in bursting at
      a defined pressure, indicating the additional contribution to mechanical
      stability by the outer layers. After 7 d culture, mechanical stability of coated
      capsules decreased in RPMI and NaCl but was most pronounced in sodium citrate.
      The capsule diameter increased in sodium citrate, less pronounced in NaCl and was
      significantly different to RPMI and double distilled water. During long-term
      culture in RPMI, the diameter increased and mechanical stability decreased
      significantly. Multilayer coating improved mechanical stability which was impeded
      most in sodium citrate, to a lesser extent by NaCl and RPMI even after long-term
      exposure.

PMID- 10919696
TI  - A twin study of communication disturbances in schizophrenia.
AB  - Relatives of schizophrenia patients have demonstrated several different types of
      subtle communication disturbances. This study used twin methodology to address
      the question of whether certain of these disturbances might be reflective of
      genetic vulnerability. Verbatim interviews from a sample of monozygotic and
      dizygotic twins in which at least one member of each twin pair had a diagnosis of
      schizophrenia were rated for three different types of referential communication
      disturbances. Monozygotic versus dizygotic nonschizophrenic co-twins were
      compared on each type of disturbance. Associations between the language variables
      and object sorting test performance also were examined. Differences among
      subjects in levels of global psychopathology were controlled. Schizophrenic
      participants showed higher levels of communication disturbance than
      nonschizophrenic co-twins. One type of communication failure, the "missing
      information" reference, discriminated monozygotic from dizygotic nonschizophrenic
      co-twins. This type of failure was associated with specific types of errors on
      the object sorting test. These findings suggest that missing information
      references may be an expression of schizophrenia-related genetic vulnerability.

PMID- 10919697
TI  - A ten-year longitudinal study of intense ambivalence as a predictor of risk for
      psychopathology.
AB  - The predictive validity of the Intense Ambivalence Scale was examined in a 10
      year longitudinal study of 362 psychometrically identified psychosis-prone and
      control participants. Elevated scores on the Intense Ambivalence Scale predicted
      psychotic-like and depressive symptoms, and the development of psychotic
      illnesses at the 10-year follow-up assessment (after the removal of variance for
      membership in the psychosis-prone and control groups). Elevated scores on the
      scale were also associated with substance abuse, schizotypal symptoms, and
      impaired functioning at both the initial and follow-up assessments. The Intense
      Ambivalence Scale did not differentially enhance the predictive power of the
      Perceptual Aberration or the Magical Ideation Scales.

PMID- 10919698
TI  - The mother-child dyad facing trauma: a developmental outlook.
AB  - The effects of trauma in children are amply documented. This paper investigated
      the relationship between children's age and posttraumatic clusters of symptoms 30
      months after the end of the Gulf War and the mother's reaction to the trauma 6
      and 30 months after the war. Fifty-one children aged 6 to 8 years (3 to 5 years
      during the war) and their mothers were interviewed. Results showed no age
      differences in the various posttraumatic symptoms of the children. Correlations
      between the children's posttraumatic symptoms and both the general and the
      specific posttraumatic symptoms of their mothers were positive and significant in
      the 6-year-olds, positive and nonsignificant in the 7-year-olds, and
      nonsignificant and mostly negative in the 8-year-olds. These findings may reflect
      the developmental changes that render the older child more autonomous and the
      younger child rigidly attached to the mother after a traumatic event.

PMID- 10919700
TI  - Associations among dissociative experiences, handedness, and demographic
      variables in a nonclinical population.
AB  - Handedness is considered an indirect marker for bilateral language capacity in
      the brain. The Edinburgh Inventory for Handedness and the Dissociative
      Experiences Scale (DES) were administered to 297 nonclinical volunteers. Female
      sex, young age, and non-right handedness accounted for 24% of the total variance
      on the DES, including both pathological and nonpathological dissociative
      experiences. This is consistent with the hypothesis that cerebral lateralization
      indicating handedness is a predisposing factor for dissociative episodes
      especially in female subjects.

PMID- 10919699
TI  - Profiling the trauma related symptoms of Bosnian refugees who have not sought
      mental health services.
AB  - The objective of this study was to profile trauma related psychiatric symptoms in
      a group of refugees not seeking mental health services and to consider the
      services implications. The study involved research assessments of two groups of
      Bosnian refugees: those who have not presented for mental health services and
      those who have. A total of 28 of 41 nonpresenters (70%) met symptom criteria for
      posttraumatic stress disorder (PTSD) diagnosis. All service presenters (N = 29)
      met symptom criteria for PTSD diagnosis. The group that did not present for
      services reported substantial but lower trauma exposure, PTSD symptom severity,
      and depression symptom severity. They had significant differences on all
      subscales of the MOS SF-36, indicating better health status. We concluded that
      those who do not seek services have substantial symptom levels, but their self
      concept appears to be less oriented toward illness and help seeking. Innovative
      access, engagement, and preventive interventions are needed to address those who
      have symptoms but do not readily seek help for trauma mental health services.

PMID- 10919701
TI  - Dissociation, schizotypy, and fantasy proneness in undergraduate students.
AB  - Previous research has noted a robust correlation between dissociation and
      schizophrenia-like symptoms. One way to interpret the relationship between
      dissociation and schizotypy is to assume that it is an artifact of fantasy
      proneness. In the present study, 152 undergraduates completed measures of
      dissociation, schizotypy, and fantasy proneness. Dissociative tendencies were
      found to be related to the full range of schizotypal features. Regression
      analysis showed that schizotypy still contributed to the prediction of
      dissociative tendencies when variance related to fantasy proneness was extracted.
      These results indicate that the close connection between dissociation and
      schizotypy cannot be interpreted in terms of an artifact produced by fantasy
      proneness. Thus, the overlap between dissociation and schizotypy warrants
      systematic study.

PMID- 10919702
TI  - Measuring overall defensive functioning with the Defense Style Questionnaire: a
      comparison of different scoring methods.
AB  - The evidence for the division of defenses measured with the Defense Style
      Questionnaire (DSQ) into immature, neurotic, and mature types appears to be
      lacking. We hypothesized that defenses can be represented unidimensionally.
      Classical multidimensional scaling was applied to the maturity ratings of items
      given by 279 experts. It appeared that the items of the DSQ can be represented
      unidimensionally. In a second study, two three-factor models of the DSQ were
      tested with confirmatory factor analysis, using scores of 543 psychiatric
      outpatients. Both three-factor models were implausible. A third study showed that
      the overall defensive functioning scores derived from the first study
      discriminated well between samples of 543 psychiatric outpatients, 69 medical
      students, and 68 graduate students attending a student counselor. We also found
      that the overall defensive functioning scores correlated positively with the
      current Global Assessment of Functioning in the psychiatric sample. We concluded
      that the DSQ is a useful instrument for measuring overall defensive functioning.

PMID- 10919703
TI  - Sexual and physical abuse of chronically ill psychiatric outpatients compared
      with a matched sample of medical outpatients.
AB  - Because there are few controlled studies, we aimed to determine the prevalence of
      sexual and physical abuse reported by psychiatric outpatients compared with
      matched controls. The sample consisted of 158 outpatients with major mental
      disorders including schizophrenia and bipolar disorder who responded to a semi
      structured interview (response rate = 64.8%) and who were individually matched
      for gender, age, and ethnicity with 158 outpatients who had never been treated
      for psychiatric illness. They answered questions about whether and when they had
      ever been sexually or physically abused, and about the type and circumstances of
      abuse. Abuse was more common during adulthood (16 years or older); 45 psychiatric
      patients (28.5%) were sexually abused and 43 (27.3%) were physically abused.
      Compared with the controls, patients were significantly more likely to report a
      history of sexual or physical abuse during adulthood (chi2 = 5.15, df = 1, p =
      .02; chi2 = 4.09, df = 1, p = .04 respectively). During adulthood, female
      patients were significantly more likely to be sexually and physically abused than
      male patients, and those sexually abused were significantly more likely to report
      a history of sexual abuse during childhood. However, patients were not
      significantly more likely to report a history of sexual or physical abuse during
      childhood compared with the controls. These findings demonstrate that
      psychiatrically ill patients are vulnerable to sexual and physical abuse during
      adulthood and underscore psychiatrists' responsibility to routinely inquire about
      abuse experiences.

PMID- 10919704
TI  - Comparing consumer and nonconsumer provided case management services for homeless
      persons with serious mental illness.
AB  - This study compared the outcomes of services provided by case managers who are
      mental health system consumers and case managers who were not consumers. The
      study focused on the first two cohorts that entered the ACCESS program, a 5-year
      demonstration program funded by the Center for Mental Health Services between
      1994 and 1996. We tested the associations between the type of case manager and
      clinical outcomes at three time points (baseline, 3 months, and 12 months). A
      series of one-way repeated measures of analyses of variance were conducted on
      clients from ACCESS sites that hired consumer providers. Although there were
      significant effects of Time for almost every outcome measure (clients improved
      over time), there were no significant Time x Case Manager Type interactions.
      Staff age, race, or gender did not significantly alter the pattern of these
      results. Given that services provided by consumers and nonconsumers were
      associated with equivalent client outcomes, the present study shows, using a
      large sample, the ability of consumers to provide mental health services as
      members of a case management team.

PMID- 10919705
TI  - Benzodiazepine use in posttraumatic stress disorder among veterans with substance
      abuse.
AB  - Veterans with posttraumatic stress disorder (PTSD) and substance abuse may abuse
      benzodiazepines and develop violent dyscontrol when using them. A total of 370
      veterans were compared by substance abuse diagnosis (50%), benzodiazepine use
      (36%), and their interaction on 1-year outcomes after inpatient discharge.
      Substance abusers were less likely to be prescribed benzodiazepines (26% vs.
      45%). No outcome showed a differential worsening by substance abuse or
      benzodiazepines, although some baseline differences were noted. Outpatient health
      care utilization was lower in benzodiazepine users (47 vs. 33 visits). Among PTSD
      patients with comorbid substance abuse, benzodiazepine treatment was not
      associated with adverse effects on outcome, but it may reduce health care
      utilization.

PMID- 10919706
TI  - A comparison of chronic combat-related posttraumatic stress disorder (PTSD)
      patients with and without a history of suicide attempt.

PMID- 10919707
TI  - Perception of spouses and relationships: a matched control study of patients with
      severe affective disorder in remission and their spouses.

PMID- 10919709
TI  - ERK signalling in metastatic human MDA-MB-231 breast carcinoma cells is adapted
      to obtain high urokinase expression and rapid cell proliferation.
AB  - Increased urokinase plasminogen activator (u-PA) production is associated with
      tumor invasion and metastasis in several malignancies, including breast cancer.
      The mechanisms underlying constitutive u-PA expression are not well understood.
      We examined the relationship between the signal strength of the ERK pathway and
      the level of u-PA expression in the metastatic human breast cancer cell line MDA
      MB-231. Treatment with the MEK1 inhibitor PD98059 resulted in decreased ERK1/2
      phosphorylation and decreased u-PA mRNA and protein expression. Inhibition of
      ERK1/2 activity also led to decreased cell proliferation and to decreased cyclin
      D1 expression. Less than 5% of total ERK1/2 was phosphorylated in exponentially
      growing MDA-MB-231 cells, and ERK1/2 activity could be stimulated by okadaic
      acid. Okadaic acid did not stimulate u-PA expression, but induced strong
      expression of the cdk-inhibitor p21Cip1. These findings suggest that ERK1/2
      signaling is tuned to a level which results in high u-PA expression and rapid
      cell proliferation.

PMID- 10919708
TI  - Functional cloning of ARM-1, an adhesion-regulating molecule upregulated in
      metastatic tumor cells.
AB  - Interactions of tumor cells with the endothelium and tissue stroma are considered
      to be critical steps in metastasis formation and progression of cancer. To
      identify cellular receptors that mediate the binding of tumor cells to
      endothelium, a murine T cell lymphoma-derived expression library was screened for
      adhesion-inducing cDNA clones. We identified a novel cell adhesion-promoting
      molecule, termed ARM-1 (adhesion regulating molecule-1), which is homologous to a
      human Mr 110,000 tumor-associated antigen. The ARM-1 cDNA codes for a type I
      transmembrane protein of 407 amino acids with potential O- and N-glycosylation
      sites that does not belong to any of the known families of cell adhesion
      molecules. Overexpression of ARM-1 in 293T human embryonic kidney cells
      significantly increased adhesion to different endothelial cells. ARM-1 expression
      in 293T cells did not alter integrin expression or beta1-integrin-mediated cell
      adhesion. Northern blot analysis of human breast cancer cell lines revealed 3- to
      5-fold elevated ARM-1 mRNA levels in metastatic as compared to non-metastatic
      cells. In conclusion, we have identified ARM-1 as a novel cell adhesion-promoting
      receptor that is upregulated in metastatic cancer cells.

PMID- 10919711
TI  - hMSH6 deficiency and inactivation of the alphaE-catenin invasion-suppressor gene
      in HCT-8 colon cancer cells.
AB  - Transition from an epithelioid (E) to a round (R) morphotype, in the human colon
      cancer cell line HCT-8, is associated with loss or truncation of alphaE-catenin
      and acquisition of invasiveness in organ culture. In E clones, like in parental
      HCT-8 cells, one allele of the alphaE-catenin gene (CTNNA1) is mutated. HCT-8
      cells have also a 'Microsatelite Instability-High' (MSI-H) phenotype presumably
      due to a mutated hMSH6 gene. Fusion of E type cells doubles the wild type CTNNA1
      alleles and prevents the loss of alphaE-catenin. Introduction of an extra
      chromosome 2, carrying a wild type hMSH6 gene, restores post-replicative mismatch
      repair and also prevents the frequent inactivation of the remaining wild type
      CTNNA1 allele.

PMID- 10919710
TI  - Phenotypic and functional characteristics of tumour-derived microvascular
      endothelial cells.
AB  - We recently developed a method for the isolation and purification of tumour
      derived endothelium. In this study the phenotypic and functional properties of
      human tumour-derived microvascular endothelial cells (TdMEC) were examined.
      Endothelium obtained from human adrenal gland specimens (HAMEC) was used as a
      reference microvascular endothelial cell population. TdMEC formed a confluent
      monolayer with the typical morphological appearance of endothelium and were
      positive for endothelial markers such as Ulex-1 lectin, CD31 antigen, von
      Willebrand Factor and VE-cadherin. The addition of acidic Fibroblast Growth
      Factor (aFGF), basic FGF (bFGF) or Vascular Endothelial Growth Factor (VEGF)
      substantially improved proliferation of TdMEC; and kidney carcinoma derived
      endothelial cells were more responsive to FGFs, whereas glioblastoma derived
      endothelial cells greatly responded to VEGF TdMEC expressed high levels of the
      VEGF receptors, KDR/flk-1 and Flt-1, as shown by northern blot analysis. TdMEC
      expressed the adhesion molecules ICAM-1, VCAM-1 and E-selectin that could be
      further increased by exposing TdMEC culture to interleukin-1. All the TdMEC
      expressed interleukin-8 mRNA. These findings show that TdMEC in vitro maintain
      several of the features described for microvasculature. Thus, TdMEC represent a
      useful tool to study markers for tumor vasculature.

PMID- 10919712
TI  - Integrin alpha4beta1/VCAM-1 pathway mediates primary adhesion of RAW117 lymphoma
      cells to hepatic sinusoidal endothelial cells under flow.
AB  - Adhesion and stabilization of circulating tumor cells to endothelial cells in
      target blood vessels play an important role in the complex process of metastasis.
      We examined the cell surface receptors involved in the liver-metastatic adhesive
      interactions of murine RAW117 large-cell lymphoma cells to unstimulated hepatic
      sinusoidal endothelial cells (HSE) under physiological flow conditions. Flow
      cytometric analysis indicated that VCAM-1, ICAM-1 and PECAM-1 are constitutively
      expressed on the surfaces of both HSE and RAW117 cells. However, monoclonal
      antibody (mAb) blockade studies showed that ICAM-1 and PECAM-1 affected neither
      the attachment nor the stabilization step of the adhesion of RAW117 cells to HSE
      cell monolayers under flow. In contrast, RAW117 cells required a significantly
      lower shear stress to establish adhesion to HSE cells when VCAM-1 receptors on
      HSE cells were blocked with mAb. Furthermore, the presence of the anti-VCAM-1 mAb
      significantly decreased the extent of adhesion compared to that of the control,
      without affecting adherent cell stabilization times. Blocking the alpha4 integrin
      subunits present mainly on RAW117 cells produced similar results to those
      previously observed with anti-VCAM-1 mAb. Although constitutively present mainly
      on the surfaces of RAW117 cells, MAdCAM-1 and beta7 integrin subunit do not
      appear to play a role in either the arrest or stabilization of RAW117 cells on
      HSE cell monolayers. However, blocking the beta1 integrin subunit on the RAW117
      H10 cells reduced adhesion to the same extent as anti-alpha4 and anti-VCAM-1
      treatments. These observations suggest that an interaction of integrin
      alpha4/beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the
      early stages of the adhesion process and may be important in liver metastasis.

PMID- 10919713
TI  - Ras-transfection up-regulated HaCaT cell migration: inhibition by Marimastat.
AB  - Cell migration is an essential process in physiological and pathological
      conditions such as wound healing and tumor invasion. This phenomenon involves
      cell adhesion on the extracellular matrix mediated by integrins, and cell
      detachment promoted in part by metalloproteinases (MMPs). In the present study,
      the migration of two HaCaT-ras clones (metastatic or not), was compared with
      HaCaT cells, and normal human primary cultured keratinocytes. Using colloidal
      gold migration assay, the migration index on type I and type IV collagen was
      similar for primary cultured keratinocytes and HaCaT, whereas it was markedly
      higher for the HaCaT-ras clones. High motility of ras-transfected cells was
      confirmed from an in vitro wound healing assay. It was not correlated with
      changes in integrin expression or related to a different adhesion on
      extracellular matrix. The Marismastat (BB-2516), a MMP inhibitor, inhibited in a
      dose-dependent effect the migration in both assays, demonstrating the important
      role of MMPs in the migration process. Under our experimental conditions, MMP-1
      activity was not detected in HaCaT and MMP-9 activity was secreted by these cells
      only after their stimulation by EGF. Here, MMP-2 was the major gelatinolytic
      activity secreted by all the cells and its secretion was markedly higher for
      HaCaT-nis clones compared with HaCaT. In addition, Western blotting results
      confirmed a higher expression of MMP-2 associated with a lower expression of TIMP
      2 in HaCaT-ras compared with HaCaT. These results suggest that Ha-ras oncogene
      could be a stimulating factor of migration and might modified the balance between
      MMP-2 and TIMP-2 in keratinocyte cell lines.

PMID- 10919714
TI  - Upregulation of vascular endothelial growth factor by cobalt chloride-simulated
      hypoxia is mediated by persistent induction of cyclooxygenase-2 in a metastatic
      human prostate cancer cell line.
AB  - Upregulation of vascular endothelial growth factor (VEGF) expression induced by
      hypoxia is crucial event leading to neovascularization. Cyclooxygenase-2, an
      inducible enzyme that catalyzes the formation of prostaglandins (PGs) from
      arachidonic acid, has been demonstrated to be induced by hypoxia and play role in
      angiogenesis and metastasis. To investigate the potential effect of COX-2 on
      hypoxia-induced VEGF expression in prostate cancer. We examined the relationship
      between COX-2 expression and VEGF induction in response to cobalt chloride
      (CoCl2)-simulated hypoxia in three human prostate cancer cell lines with
      differing biological phenotypes. Northern blotting and ELISA revealed that all
      three tested cell lines constitutively expressed VEGF mRNA, and secreted VEGF
      protein to different degrees (LNCaP > PC-3 > PC3ML). However, these cell lines
      differed in the ability to produce VEGF in the presence of CoCl2-simulated
      hypoxia. CoCl2 treatment resulted in 40% and 75% increases in VEGF mRNA, and 50%
      and 95% in protein secretion by LNCaP and PC-3 cell lines, respectively. In
      contrast, PC-3ML cell line, a PC-3 subline with highly invasive, metastatic
      phenotype, exhibits a dramatic upregulation of VEGF, 5.6-fold in mRNA and 6.3
      fold in protein secretion after treatment with CoCl2. The upregulation of VEGF in
      PC-3ML cells is accompanied by a persistent induction of COX-2 mRNA (6.5-fold)
      and protein (5-fold). Whereas COX-2 expression is only transiently induced in PC
      3 cells and not affected by CoCl2 in LNCaP cells. Moreover, the increases in VEGF
      mRNA and protein secretion induced by CoCl2 in PC-3ML cells were significantly
      suppressed following exposure to NS398, a selective COX-2 inhibitor. Finally, the
      effect of COX-2 inhibition on CoCl2-induced VEGF production was reversed by the
      treatment with exogenous PGE2. Our data demonstrate that VEGF induction by cobalt
      chloride-simulated hypoxia is maintained by a concomitant, persistent induction
      of COX-2 expression and sustained elevation of PGE2 synthesis in a human
      metastatic prostate cancer cell line, and suggest that COX-2 activity, reflected
      by PGE2 production, is involved in hypoxia-induced VEGF expression, and thus,
      modulates prostatic tumor angiogenesis.

PMID- 10919715
TI  - Infiltrative capacity of T leukemia cell lines: a distinct functional property
      coupled to expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor
      of metalloproteinases-1 (TIMP-1).
AB  - Infiltrative capacity was found to distinguish separate T leukemia cell lines. Of
      seven T-cell lines four exhibited capacity to infiltrate Matrigel. Analysis of
      infiltration was performed at the single-cell level throughout the Matrigel using
      a depth meter. Further, we examined differences in migration capacity and
      metalloproteinase production between infiltrating and non-infiltrating T-cell
      lines. The capacity to infiltrate was not directly correlated to the capacity to
      adhere to the Matrigel or to migrate on/to extracellular matrix components. It is
      concluded that infiltration capacity does not simply reflect capacity to migrate
      but represents a distinct functional property. The production of
      metalloproteinases and their inhibitors by the separate T-cell lines was analyzed
      using rt PCR, biosynthetic labelling, zymography, immunoprecipitation and ELISA.
      All T-cell lines with capacity to infiltrate produced matrix metalloproteinase-9
      (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) while non
      infiltrating cell lines did not express MMP-9. Expression of MMP-1, 2, 3, 10, 14
      and 17 showed no correlation to capacity to infiltrate. Analysis of infiltration
      in the presence of a metalloprotease inhibitor showed an increased number of
      cells within the gel. This enhancement of infiltration suggests that the function
      of MMPs and/or their inhibitors in lymphocyte infiltration is more complex than
      previously thought.

PMID- 10919717
TI  - Soluble fibrin augments platelet/tumor cell adherence in vitro and in vivo, and
      enhances experimental metastasis.
AB  - There is considerable evidence for a relationship between hemostasis and
      malignancy. Since platelet adhesion to tumor cells has been implicated in the
      metastatic process and plasma levels of fibrinogen (Fg) and soluble fibrin (sFn)
      monomer are increased in cancer, we hypothesized that these molecules might
      enhance tumor-platelet interaction. We therefore studied binding of sFn monomer
      to tumor cells in a static microplate adhesion assay and determined the effect of
      pre-treating tumor cells with sFn on tumor cell-induced thrombocytopenia and
      experimental metastasis. Soluble fibrin (produced by adding thrombin to FXIII-
      and plasminogen-free Fg in the presence of Gly-Pro-Arg-Pro-amide (GPRP-NH2)
      significantly increased platelet adherence to tumor cells. This effect was
      primarily mediated by the integrins alphaIIb beta3 on the platelet and CD 54
      (ICAM-1) on the tumor cells. Platelets adhered to untreated A375 cells (28 +/- 8
      platelets/tumor cell) and this was not significantly affected by pre-treatment of
      the tumor cells with fibrinogen or GPRP-NH2. Although thrombin treatment
      increased adherence, pre-incubation of the tumor cells with sFn resulted in a
      further increase in platelet binding to tumor cells. In contrast to untreated
      tumor cells, intravenous injection of sFn-treated A 375 cells reduced the
      platelet count in anticoagulated mice, supporting the in vitro finding that sFn
      enhanced tumor cell-platelet adherence. In a more aggressive model of
      experimental metastasis, treating tumor cells with sFn enhanced lung seeding by
      65% compared to untreated cells. Extrapolation of our data to the clinical
      situation suggests that coagulation activation, and subsequent increase in
      circulating Fn monomer, may enhance platelet adhesion to circulating tumor cells
      and thereby facilitate metastatic spread.

PMID- 10919716
TI  - Role of the cytoskeleton in adhesion stabilization of human colorectal carcinoma
      cells to extracellular matrix components under dynamic conditions of laminar
      flow.
AB  - Adhesion stabilization of malignant cells in the microcirculation is necessary
      for successful metastasis formation. The adhesion of colon carcinoma cells to
      microcirculation extracellular matrix (ECM) components is mediated, in part, by
      integrins that can be intracellularly linked to cytoskeletal proteins. Thus the
      functional status of at least certain integrins can be regulated by complex
      interactions with cytosolic, cytoskeletal and membrane-bound proteins. Wall shear
      stress caused by fluid flow also influences cellular functions, such as cell
      morphology, cytoskeletal arrangements and cell signaling. Using a parallel plate
      laminar flow chamber dynamic adhesion of human HT-29 colon carcinoma cells to
      collagen was investigated and compared with cell adhesion under static
      conditions. Cells were pretreated with cytochalasin D, nocodazole, colchicine or
      acrylamide to disrupt actin filaments, microtubules or intermediate filaments.
      Disruption of actin filaments completely inhibited all types of adhesive
      interactions. In contrast, impairment of tubulin polymerization or disruption of
      intermediate filaments resulted in different effects on static and dynamic
      adhesion. Treatment with acrylamide did not interfere with dynamic cell adhesion,
      whereas under static conditions it partially reduced adhesion rates. Under
      dynamic conditions increased initial adhesive interactions between HT-29 cells
      and collagen were found after disruption of microtubules, and the adherent cells
      demonstrated extensive crawling on collagen surfaces. In contrast, under static
      adhesion disrupting microtubules did not affect cell adhesion rates. Cytochalasin
      D and acrylamide were found to inhibit Tyr-phosphorylation of FAK and paxillin,
      whereas microtubule disrupting agents at low but not high concentrations
      increased phosphorylation of these focal adhesion proteins. Our results revealed
      that cytoskeletal components appear to be involved in adhesion stabilization of
      HT-29 cells to ECM components, and hydrodynamic shear forces modulate this
      involvement. Tyr-phosphorylation of focal adhesion proteins, such as paxillin and
      FAK, appears to be a part of this cytoskeleton-mediated process.

PMID- 10919718
TI  - Sex-chromosome pairing through heterochromatin in the African rodent Lemniscomys
      barbarus (Rodentia, Muridae). A synaptonemal complex study.
AB  - Giemsa-stained spread preparations and microspread preparations of Lemniscomys
      barbarus spermatocytes were made to investigate the meiotic behaviour of the
      peculiar sex chromosomes of this species. A typical sex vesicle is absent, as the
      X and Y chromosomes appear unfolded at zygotene and pachytene. In most cells, the
      sex chromosomes are associated at distal segments at metaphase I, probably as a
      consequence of a distal chiasma. The pairing segment is located in the
      heterochromatic regions of both sex chromosomes, which include silent ribosomal
      cistrons interspersed throughout the heterochromatin. This may suggest a possible
      involvement of ribosomal genes in both pairing and recombination processes. X-Y
      pairing proceeds beyond the pseudoautosomal region, thus involving heterologous
      segments of the differential regions, a fact that is clearly evident at the Y
      centromeric region.

PMID- 10919720
TI  - Comparative chromosome banding analysis of three South American species of rice
      rats of the genus Oryzomys (Rodentia, Sigmodontinae).
AB  - Comparative G- and C-banding analysis in three species of rice rats, namely
      Oryzomys megacephalus from Peru and French Guiana, O. yunganus (Peru) and O.
      nitidus (Bolivia) was carried out. It revealed that Peruvian O. megacephalus (2N
      = 52, NFa = 62) and that from French Guiana (2N = 54, NFa = 64) differ from each
      other by one Rb translocation and one heterochromatic arm addition/deletion.
      Three further Rb translocations separate them from O. yunganus (2N = 58, NFa =
      62). Only 16 out of 39 autosomal pairs of O. nitidus (2N = 80, NFa = 86) shared
      homologous banding patterns with O. yunganus, 4 of which were involved in tandem
      translocations to form the larger chromosomes in two other taxa. The study
      suggests that O. megacephalus, O. yunganus and O. laticeps studied previously
      form a monophyletic group in good agreement with earlier molecular and
      morphological data. By contrast, the limited homologous banding patterns found
      between them and O. nitidus cast doubt on its belonging to the same phylogenetic
      lineage. In the light of available chromosomal and molecular data, the
      significance of intra- and interspecies karyotypic variability within Oryzomys
      and its relevance to systematics and phylogeny of the genus are discussed.

PMID- 10919719
TI  - FISH to mitotic chromosomes and extended DNA fibres of Beta procumbens in a
      series of monosomic additions to beet (B. vulgaris).
AB  - The physical localization and organization of a Procumbentes-specific repetitive
      DNA sequence, PB6-4, on the chromosomes of Beta procumbens (2n = 18) were
      studied, using FISH (fluorescence in situ hybridization) to mitotic chromosomes
      and extended DNA fibres. The chromosomes of B. procumbens were studied in
      metaphase complements of the species itself, as well as in preparations of a
      series of eight different B. procumbens-derived monosomic additions to B.
      vulgaris (2n = 18). FISH to chromosome spreads of B. procumbens revealed that PB6
      4 hybridizes to all chromosomes, predominantly in the pericentromeric regions,
      but with differences in size and brightness of the signals. Hybridization of PB6
      4 to metaphase complements of B. vulgaris revealed no signals, indicating that
      cross-hybridization with the genome of this species was negligible. Consequently,
      hybridization of PB6-4 to metaphase complements of the monosomic additions
      yielded fluorescent signals on the alien chromosomes only. The previously
      observed differences in size and brightness of the fluorescent spots were
      confirmed using the single alien chromosomes. FISH of PB6-4 to extended DNA
      fibres of the monosomic additions indicated differences in the fluorescent track
      lengths between the alien chromosomes. Measurements of the fluorescent tracts
      allowed classification into discrete groups, varying from one to three groups per
      B. procumbens chromosome. The data revealed that the brightness or size of the
      signal at mitotic metaphase and the length of the fluorescent tracks on the DNA
      fibres were correlated.

PMID- 10919721
TI  - Inactive ribosomal cistrons are spread throughout the B chromosomes of Rattus
      rattus (Rodentia, Muridae). Implications for their origin and evolution.
AB  - In-situ hybridization with a rDNA probe has demonstrated the presence of non
      transcribed ribosomal genes in the B chromosomes of the black rat Rattus rattus.
      To test whether methylation of ribosomal DNA present in the B chromosomes could
      account for their inactivation, we performed in-situ digestions and Southern
      analyses of DNA digested with the isoschizomers MspI and HpaII. Our results
      suggest that the accessory chromosomes of this species have originated from one
      of the smaller NOR-carrying chromosome pairs. In the course of evolution,
      repetitive sequences invaded this supernumerary element and its ribosomal DNA
      content was dispersed throughout the chromosome and inactivated by
      heterochromatinization and methylation.

PMID- 10919722
TI  - Physical mapping, expression patterns and interphase organisation of rDNA loci in
      Portuguese endemic Silene cintrana and Silene rothmaleri.
AB  - Double target in situ hybridization to root tip metaphase and interphase cells of
      Silene cintrana and Silene rothmaleri was used to allocate the position of 18S
      5.8S-25S and 5S rRNA genes. In both species, the 18S-5.8S-25S rDNA probe labelled
      four sites located on the short arms of two submetacentric chromosomes. Only one
      locus for 5S rDNA was mapped adjacent to 18S-5.8S-25S genes in a subterminal
      position on the centromere side: in S. rothmaleri the 5S rDNA locus was adjacent
      to the small 18S-5.8S-25S locus while in S. cintrana it was near the large one.
      The NOR activity analysed by Ag-staining in metaphase cells revealed
      proportionality between in situ labelling dimensions and Ag-NORs. In both species
      all rDNA loci were potentially active, although in S. rothmaleri a tendency for
      the expression of only one locus was observed. Interphase organisation analysis
      of rDNA showed some differences between both species that were correlated with
      NOR activity.

PMID- 10919723
TI  - Human monochromosome hybrid cell panel characterized by FISH in the JCRB/HSRRB.
AB  - The human monochromosome hybrid cell panel in the Japanese Collection of Research
      Bioresources (JCRB) consists of 23 mouse cell clones, each containing a different
      human chromosome (the Y chromosome is not yet included). The panel is currently
      distributed by the Human Science Research Resources Bank (HSRRB) in Osaka. In
      order to determine the state of the human chromosomes and to supply the
      information to investigators, we characterized the cells by fluorescence in-situ
      hybridization (FISH) with corresponding human chromosome-specific painting
      probes, and, in part, by reverse FISH with the hybrid total DNA hybridized onto
      human metaphase spreads. Here, we report the frequency of intact human
      chromosomes maintained in each hybrid and the retained subregions of
      corresponding human chromosomes with relative frequencies estimated by
      fluorescent intensity. We used specific painted patterns to classify each hybrid
      into tentative types with their frequencies showing the nature of each hybrid and
      the state of rearrangements. This characterization will provide valuable
      information to investigators using the panel.

PMID- 10919724
TI  - Sex chromosome evolution in fish. II. Second occurrence of an X1X2Y sex
      chromosome system in Gymnotiformes.
AB  - A multiple sex chromosome system of the X1X1X2X2:X1X2Y type is reported to occur
      in the fish species Brachyhypopomus pinnicaudatus (Gymnotiformes, Hypopomidae),
      being the second occurrence of this sex chromosome system in Gymnotiformes and
      the fifth among Neotropical freshwater fish. The possible origin of this system
      was hypothesized to be a centric fusion, which occurred in an ancestral form, of
      two medium-sized acrocentrics, giving origin to the metacentric neo-Y.
      Heterochromatic DAPI-positive regions were visualized in the pericentromeric
      region of all the chromosomes, including the Y-chromosome. In-situ hybridization
      with (TTAGGG)n (all-human-telomeres probe) did not detect any telomeric
      interstitial regions (ITS), indicating a possible loss of terminal segments of
      the chromosomes involved in the neo-Y formation.

PMID- 10919725
TI  - Modification of wheat rDNA loci by rye B chromosomes: a chromatin organization
      model.
AB  - The rDNA loci, and their associated NORs, on chromosomes 1B and 6B of the
      hexaploid wheat cv. Lindstrom have been used as a chromatin marker to investigate
      the functional basis of the phenotype effects of introgressed supernumerary B
      chromosomes (Bs) of rye. The rye Bs themselves lack genes, other than those which
      determine their mitotic drive mechanism, and the way in which they can modulate
      characters determined by the A chromosome background has always been a puzzle. An
      isogenic line of Lindstrom plants carrying different numbers of Bs was used as
      the experimental system to see how different doses of Bs (from 0 to 6) affected
      the activity of the wheat NORs and the organization of their rDNA loci at
      interphase. Silver staining on metaphase chromosomes was used to evaluate the
      previous activity of the NORs, and to reveal variations in their size; and the
      pTa71 FISH probe from wheat was used to visualize structural modifications to the
      interphase rDNA loci. A single B had no measurable effect, but, as the B-number
      increased, there were significant changes in the physical dimensions of the
      metaphase NORs, reflecting reduced levels of their activity earlier in the cell
      cycle, and also in the condensation patterns of the interphase rDNA loci. In
      addition, the higher B-numbers caused a size heteromorphism between the
      homologous NORs. A model is discussed which interprets the phenotypic effects of
      Bs generically, in nucleotypic terms, based of their being 'genetically inert'
      but 'chromosomally active'.

PMID- 10919726
TI  - Conservative distribution of 5S rDNA loci in Schizodon (Pisces, Anostomidae)
      chromosomes.

PMID- 10919727
TI  - Variant centromere lacking specific molecular traits in the Sykes monkey.

PMID- 10919728
TI  - Horse v-fes feline sarcoma viral oncogene homologue; pyruvate kinase, muscle type
      2; plasminogen; beta spectrin, non-erythrocytic 1; thymidylate synthetase; and
      microsatellite LEX078 map to 1q14-q15, 1q21, 31q12-q14, 15q22, 8q12-q14, and
      14q27, respectively.

PMID- 10919729
TI  - Zebrafish 5S rRNA genes map to the long arms of chromosome 3.

PMID- 10919730
TI  - Out of the mouths of babes: oral premalignant lesions and use of alternative
      tobacco products.

PMID- 10919731
TI  - Chewing tobacco, alcohol, and the risk of erythroplakia.
AB  - Although chewing tobacco, smoking, and alcohol drinking have been suggested as
      risk factors for oral cancer, no study has examined the relationship between
      those factors and the risk of erythroplakia, an uncommon but severe oral
      premalignant lesion. In this study, we have analyzed the effects of chewing
      tobacco, smoking, alcohol drinking, body mass index, and vegetable, fruit, and
      vitamin/iron intake on the risk of erythroplakia and explored potential
      interactions between those factors in an Indian population. A case-control study
      including 100 erythroplakia cases and 47,773 controls was conducted, as part of
      an on-going randomized oral cancer screening trial in Kerala, India. The analysis
      was based on the data from the baseline screening for the intervention group,
      where the diagnostic information was available. The information on
      epidemiological risk factors was collected with interviews conducted by trained
      health workers. The erythroplakia cases were identified by health workers with
      oral visual inspections, and then confirmed by dentists and oncologists who made
      the final diagnosis. The odds ratios (OR) and their 95% confidence intervals
      (CIs) were calculated by the logistic regression model using SAS software. The
      adjusted OR for erythroplakia was 19.8 (95% CI, 9.8-40.0) for individuals who had
      ever chewed tobacco, after controlling for age, sex, education, body mass index,
      smoking, and drinking. The adjusted OR for ever-alcohol-drinkers was 3.0 (95% CI,
      1.6-5.7) after controlling for age, sex, education, body mass index, chewing
      tobacco, and smoking. For ever-smokers, the adjusted OR was 1.6 (95% CI, 0.9
      2.9). A more than additive interaction on the risk of erythroplakia was suggested
      between tobacco chewing and low vegetable intake, whereas a more than
      multiplicative interaction was indicated between alcohol drinking and low
      vegetable intake, and between drinking and low fruit intake. We concluded that
      tobacco chewing and alcohol drinking are strong risk factors for erythroplakia in
      the Indian population. Because the CIs of interaction terms were wide and
      overlapping with those of the main effects, only potential interactions are
      suggested.

PMID- 10919732
TI  - The effects of vitamin C and vitamin E on oxidative DNA damage: results from a
      randomized controlled trial.
AB  - Oxidative DNA damage may be important in mutagenic, carcinogenic, and aging
      processes. Although it is plausible that antioxidant vitamins may reduce
      oxidative DNA damage, evidence from human studies has been sparse and
      inconsistent. We determined the short-term effects of vitamin C (500 mg/day) and
      vitamin E (400 IU d-alpha-tocopheryl acetate/day) supplements on oxidative DNA
      damage in a double-masked, placebo-controlled, 2x2 factorial trial in 184
      nonsmoking adults. Mean duration of supplementation was 2 months. Oxidative DNA
      damage was measured by 24-h urinary excretion of 8-hydroxy-2'-deoxyguanosine (8
      OHdG). At baseline, urinary 8-OHdG (mean +/- SE; ng/mg creatinine) was associated
      with race (15.6 +/- 0.8 in African Americans versus 20.3 +/- 1.2 in Caucasians, P
      = 0.001), prior antioxidant supplement use (18.6 +/- 0.8 in users versus 13.8 +/-
      1.5 in non-users, P = 0.007), and regular exercise (19.2 +/- 1.1 in exercisers
      versus 16.6 +/- 0.9 in non-exercisers, P = 0.04). Fruit and vegetable intake and
      serum ascorbic acid were inversely associated with urinary 8-OHdG (P-trend = 0.02
      and 0.016, respectively). The benefits of fruit and vegetable intake became
      evident with the consumption being at least three servings/day. At the end of
      supplementation, change from baseline in urinary 8-OHdG (mean +/- SE; ng/mg
      creatinine) was -0.6 +/- 1.4 (P = 0.61), 0.6 +/- 1.1 (P = 0.59), 0.5 +/- 1.0 (P =
      0.61), and 1.6 +/- 1.4 (P = 0.27) in the placebo, vitamin C alone, vitamin E
      alone, and combined vitamins C and E groups, respectively. In overall and
      subgroup analyses, there was no significant main effect or interaction effect of
      the supplements on urinary 8-OHdG. In conclusion, supplementation of diet with
      vitamin C (500 mg/day) and vitamin E (400 IU d-alpha-tocopheryl acetate/day) had
      no significant main effect or interaction effect on oxidative DNA damage as
      measured by urinary 8-OHdG in nonsmoking adults. However, several aspects of a
      healthy lifestyle were associated with lower oxidative DNA damage.

PMID- 10919733
TI  - Rectal mucosal proliferation and risk of colorectal adenomas: results from a
      randomized controlled trial.
AB  - Although rectal mucosal labeling index is thought to be a useful surrogate
      biomarker for colorectal cancer, the ability of the index to predict future
      neoplasia is unclear. We obtained rectal mucosal biopsies from 333 participants
      of a randomized controlled chemoprevention trial of calcium supplementation to
      determine whether labeling index was correlated with concurrent or future
      colorectal neoplasms. Labeling index was measured using proliferating cell
      nuclear antigen immunohistochemistry. Adenomas were enumerated at the time of the
      biopsies (cross-sectional) and 3 years later (prospective). We used logistic
      regression to test for an association of adenoma occurrence with overall labeling
      index, the mean proliferative height, and labeling index in the upper 40% of
      colon crypts. In the cross-sectional analysis, we found indications that higher
      proliferation was associated with an increase in the prevalence of adenomas. The
      overall adjusted odds ratios (OR) (95% confidence interval) were 1.14 (0.90-1.45)
      per % crypt labeling index, OR 1.08 (0.99-1.19) for upper crypt proliferation,
      and OR 1.07 (1.03-1.12) for proliferative height. In contrast, individuals with
      higher labeling index at baseline were actually less likely to have adenomas in
      the prospective analyses: OR 0.80 (0.62-1.02) per % crypt labeling index, OR 0.86
      (0.73-1.00) for upper crypt index, and OR 0.97 (0.93-1.01) for proliferative
      height. Proliferative index does not predict future colorectal neoplasia,
      although it may be weakly associated with the presence of current adenomas. These
      results have important implications for the design of future intervention
      studies. Although it may be attractive to include the measurement of intermediate
      markers in large controlled trials, until we have more confidence in their
      performance, we should rely on better proven and more reliable intermediates,
      such as adenomas.

PMID- 10919734
TI  - The methylenetetrahydrofolate reductase 677C-->T polymorphism and distal
      colorectal adenoma risk.
AB  - A common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene,
      where a cytosine at nucleotide 677 is replaced by a thymine (677C-->T), is
      associated with enzyme thermolability and a reduction in the conversion of 5,10
      methyltetrahydrofolate (5,10-MTHF) into 5-methyltetrahydrofolate. We assessed the
      association between homozygosity for the MTHFR 677CT genotype (TT) and colorectal
      adenoma risk in a large sigmoidoscopy-based case-control study of members of a
      prepaid health plan in Los Angeles. MTHFR genotype was determined for 471 cases
      and 510 age-, sex-, clinic-, and sigmoidoscopy-date-matched controls. Information
      on RBC and plasma folate levels were analyzed for 331 cases and 350 controls.
      When compared with the presence of at least one wild-type allele (CT/CC), the
      odds ratio (OR) for the TT genotype was 1.19 [95% confidence interval (CI), 0.77
      1.76] after adjusting for race and the matching factors. Compared with those in
      the lowest quartiles of RBC and plasma folate and a wild-type allele, adenoma
      risk was increased for TT homozygotes in the lowest folate quartiles (genotype:
      OR, 2.04 and 95% CI, 0.6-7.0; OR, 1.84 and 95% CI, 0.6-7.0 for RBCs and plasma
      folate, respectively) and decreased in TT homozygotes in the highest quartiles
      (genotype: OR, 0.82 and 95% CI, 0.32-2.10; OR, 0.65 and 95% CI, 0.22-1.95,
      respectively). There was also a significant interaction between TT genotype and
      the increased adenoma risk associated with alcohol. These data are consistent
      with an interaction between MTHFR genotype and folate availability.

PMID- 10919735
TI  - Explaining physician rates of providing flexible sigmoidoscopy.
AB  - Colorectal cancer is the third most frequent cancer, yet screening rates for this
      cancer remain low. This study was designed to identify factors associated with
      family physicians' rates of recommending or providing flexible sigmoidoscopy. We
      applied a behavioral model consisting of three components: physician attitude
      toward providing the test, facilitating conditions, and reinforcing conditions.
      Qualitative interviews identified relevant measures of each model component and
      guided the design of the survey. The survey was administered to 60 randomly
      selected family physicians in Washington State. Chart reviews were conducted to
      measure physician rates of providing flexible sigmoidoscopy. All three model
      components were significantly correlated with sigmoidoscopy rate. Multiple
      regression found physician attitude, facilitating conditions, and their
      interaction to be significant determinants of sigmoidoscopy rate (multiple R =
      0.72). Analyses of specific items used to measure physician attitude found that
      physician beliefs about cost, time, income, degree of distaste, risk of
      complications, and screening effectiveness were significantly correlated with
      sigmoidoscopy rate. Specific facilitating conditions found to be correlated with
      rate of providing the test included physician and staff training, availability of
      a reminder system, and clinic structural conditions. This study provides strong
      support for application of a theory-based model to understand physician provision
      of flexible sigmoidoscopy testing for colorectal cancer. The findings provide
      very specific information to guide development of educational and motivational
      efforts and modification of facilitating conditions to increase physician
      provision of sigmoidoscopy to control colorectal cancer.

PMID- 10919736
TI  - Lewis antigen alterations in a population at high risk of stomach cancer.
AB  - Anomalous Lewis(a) antigen and sulfomucin expression are considered as markers of
      progression in precursor lesions of gastric cancer. Additionally, Lewis antigen
      and secretor phenotype have been related to Helicobacter pylori infection and
      gastric epithelial damage. The two objectives of this study were to correlate
      Lewis antigen alterations with histochemical changes and to explore the
      relationship between Lewis and secretor phenotypes and gastric epithelial damage
      related to H. pylori infection. The study subjects were selected from a
      chemoprevention trial in Tachira State, Venezuela, an area with a high risk of
      gastric cancer. Anomalous Lewis(a) antigen expression in Lewis (a-b+) phenotype
      individuals was closely related to the severity of the histological lesions,
      especially to dysplasia and type III intestinal metaplasia lesions. A weak
      relationship was observed between nonsecretor individuals and more advanced
      lesions of IM, but this association was not statistically significant. There was
      no relationship between secretor phenotype and H. pylori status, atrophy,
      regenerative activity, erosion, or ulcer.

PMID- 10919737
TI  - Cytochrome P450 2E1 polymorphism in gastric cancer in Brazil: case-control
      studies of Japanese Brazilians and non-Japanese Brazilians.
AB  - Cytochrome P450 2E1 (Cyp2E1) is involved in the metabolic oxidation of
      carcinogenic nitroso compounds, including N-nitrosoamines. There is an RsaI
      polymorphism in the transcriptional regulatory region of this gene, and in vitro
      evidence suggests that the variant type of this polymorphic site has higher
      transcriptional activity but less chlorzoxazone-metabolizing activity.
      Interindividual differences in the metabolic capacity of Cyp2E1 are assumed to be
      associated with cancer susceptibility, but the results of the previous studies on
      the relation between Cyp2E1 RsaI polymorphism and cancer susceptibility have been
      inconsistent. Two case-control studies of gastric cancer in Japanese Brazilians
      (96 cases, 192 controls) and Brazilians not of Japanese ancestry (non-Japanese
      Brazilians; 236 cases, 236 controls) in Sao Paulo were designed to clarify the
      role of the Cyp2E1 RsaI genotype in susceptibility to gastric cancer after
      considering multifactorial environmental influences. The subjects with variant
      RsaI genotypes amounted to 47% (28 of 59) and 48% (64 of 133), respectively, of
      the Japanese cases and controls, and 6% (11 of 187) and 10% (19 of 192),
      respectively, of the non-Japanese cases and controls. As expected, a difference
      in the distributions of the two groups was observed. The odds ratio of the RsaI
      variant genotype of Cyp2E1 was 0.46 (95% confidence interval, 0.21-1.04) in the
      non-Japanese Brazilian population and 0.98 (95% confidence interval, 0.50-1.90)
      in the Japanese Brazilian population after adjusting for sex, age, tobacco use,
      and meat consumption. Additional adjustment for potential confounding factors did
      not change the odds ratio substantially. No significant interactions were
      observed between the polymorphism and environmental factors. In regard to the
      histological type of gastric cancer, the variant genotype was significantly more
      prevalent than the common genotype in Japanese subjects with diffuse type gastric
      cancer. Our study suggests that the Cyp2E1 RsaI polymorphism is associated with a
      reduced risk of gastric cancer, although how the assumed increase in Cyp2E1
      expression produced by this polymorphism is related to a reduced risk of cancer
      remains unclear. The observations in this study are consistent with the recent
      observations of esophageal cancer in endemic areas of China.

PMID- 10919738
TI  - Body size, physical activity, and breast cancer hormone receptor status: results
      from two case-control studies.
AB  - We evaluated whether our previous reports of increased postmenopausal breast
      cancer risk with higher body mass index (BMI) or of reduced premenopausal and
      postmenopausal breast cancer risk with higher physical activity levels varied
      according to the tumor's estrogen receptor (ER) and progesterone receptor (PR)
      status. Participants enrolled in either of two population-based case-control
      studies in Los Angeles County, California: one of premenopausal women (ages < or
      = 40 years), and one of postmenopausal women (ages 55-64 years). Case
      participants were diagnosed for the first time with in situ or invasive breast
      cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through
      12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424
      premenopausal and 760 postmenopausal case participants. The analysis included 714
      premenopausal and 1091 postmenopausal age-matched, race-matched (white or
      Hispanic), parity-matched (premenopausal women only), and residential
      neighborhood-matched control participants. Among the postmenopausal women,
      obesity was associated with an increased odds of ER+/PR+ breast cancer (odds
      ratio, 2.45 for women in the highest versus the lowest body mass index quartile;
      95% confidence interval, 1.73-3.47). Body mass index was associated with neither
      ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among
      the premenopausal women. For both premenopausal and postmenopausal women, higher
      recreational physical activity levels (> or = 17.6 MET-hours/week versus no
      activity) were associated with a 30-60% reduction in risk of nearly all ER/PR
      subtypes, although the associations were generally of borderline statistical
      significance. Examining these potentially modifiable breast cancer risk factors
      by tumor ER and PR status may provide us with greater insight into breast cancer
      etiology and the mechanisms underlying the risk factor associations.

PMID- 10919739
TI  - Induction of apoptosis by conjugated linoleic acid in cultured mammary tumor
      cells and premalignant lesions of the rat mammary gland.
AB  - Conjugated linoleic acid (CLA) is an effective agent in preventing mammary cancer
      in rats treated with a carcinogen. The appearance of a tumor mass is the net
      result of cell proliferation minus cell death. Thus, apoptosis could be an
      important mechanism in controlling clonal expansion of the early premalignant
      lesions. The overall objective of this report was to determine whether CLA
      stimulated apoptosis. In the first part of the study, CLA was found to increase
      chromatin condensation (visualized through fluorescent 4',6-diamidino-2
      phenylindole staining to DNA) and to induce DNA laddering, both evidence of
      apoptosis, in a rat mammary tumor cell line. The second part was to investigate
      the effect of CLA feeding on the development of histologically identifiable
      premalignant lesions in the rat mammary gland, as well as on the quantification
      of apoptosis (by terminal uridyltransferase nick end labeling assay) and the
      expression by immunohistochemistry of apoptosis regulatory proteins (bcl-2, bak,
      and bax) in normal versus premalignant mammary structures. CLA inhibited the
      formation of premalignant lesions by approximately 50%. It also significantly
      increased apoptosis and reduced the expression of bcl-2 in these lesions, but it
      did not modulate the levels of bak or bax. In contrast, neither apoptosis nor any
      of the apoptosis regulatory proteins was affected by CLA in normal mammary gland
      alveoli or terminal end buds. The data suggest that early pathological lesions
      may be particularly sensitive to CLA. In addition to providing a molecular basis
      for elucidating the mechanism of action of CLA in cancer prevention, the research
      on CLA-responsive biomarkers also has a practical side because these assays can
      be applied to biopsied human tissue samples in future CLA intervention trials.

PMID- 10919740
TI  - Risk factors for carcinoma in situ of the breast.
AB  - As more women obtain screening mammograms regularly and at younger ages, the
      diagnosis of breast carcinoma in situ becomes more frequent. To examine whether
      risk factors for carcinoma in situ correspond with risk factors for invasive
      breast cancer, we analyzed data from a population-based case-control study
      conducted in 1988-1990. We identified newly diagnosed cases of carcinoma in situ
      (n = 301) and invasive breast cancer (n = 3789) in women 18-74 years of age from
      Wisconsin's statewide tumor registry. Cases and population controls (n = 3999)
      completed structured telephone interviews. Overall, associations with risk of
      carcinoma in situ in relation to many reproductive life-style risk factors were
      similar to those associated with risk of invasive disease. Women who reported a
      family history of breast cancer had a 2-fold elevated risk of carcinoma in situ
      (odds ratio, 2.67; 95% confidence interval, 2.00-3.57). Personal history of
      benign biopsied breast disease also increased risk of carcinoma in situ (odds
      ratio, 2.19; 95% confidence interval, 1.62-2.95). Subgroup analysis suggested
      that high vitamin A intake and high alcohol intake may be associated with risk of
      ductal but not lobular carcinoma in situ. These data support the presence of
      common risk factors between in situ and invasive breast cancer.

PMID- 10919743
TI  - The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites
      in premenopausal women.
AB  - Estrogen is metabolized along two competing pathways to form the 2-hydroxylated
      and the 16alpha-hydroxylated metabolites. Based on proposed differences in
      biological activities, the ratio of these metabolites, 2-hydroxyestrogen:16alpha
      hydroxyestrone (2:16alpha-OHE1), has been used as a biomarker for breast cancer
      risk. Women with an elevated 2:16alpha-OHE1 ratio are hypothesized to be at a
      decreased risk of breast cancer. Flaxseed, the most significant source of plant
      lignans, and wheat bran, an excellent source of dietary fiber, have both been
      shown to have chemoprotective benefits. Some of these benefits may be
      attributable to their influence on endogenous sex hormone production and
      metabolism. We examined the effect of flaxseed consumption alone and in
      combination with wheat bran on urinary estrogen metabolites in premenopausal
      women. Sixteen premenopausal women were studied for four feeding treatments
      lasting two menstrual cycles each in a randomized cross-over design. During the
      four feeding treatments, subjects consumed their usual diets supplemented with
      baked goods containing no flaxseed or wheat bran, 10 g of flaxseed, 28 g of wheat
      bran, or 10 g of flaxseed plus 28 g of wheat bran/day. Urinary excretion of 2
      hydroxyestrogen and 16alpha-hydroxyestrone, as well as their ratio, 2:16alpha
      OHE1, were measured by enzyme immunoassay. Flaxseed supplementation significantly
      increased the urinary 2:16alpha-OHE1 ratio (P = 0.034), but wheat bran had no
      effect. These results suggest that flaxseed may be chemoprotective in
      premenopausal women.

PMID- 10919741
TI  - Hemoglobin adducts from acrylonitrile and ethylene oxide in cigarette smokers:
      effects of glutathione S-transferase T1-null and M1-null genotypes.
AB  - Acrylonitrile (ACN) is used to manufacture plastics and fibers. It is
      carcinogenic in rats and is found in cigarette smoke. Ethylene oxide (EO) is a
      metabolite of ethylene, also found in cigarette smoke, and is carcinogenic in
      rodents. Both ACN and EO undergo conjugation with glutathione. The objectives of
      this study were to examine the relationship between cigarette smoking and
      hemoglobin adducts derived from ACN and EO and to investigate whether null
      genotypes for glutathione transferase (GSTM1 and GSTT1) alter the internal dose
      of these agents. The hemoglobin adducts N-(2-cyanoethyl)valine (CEVal), which is
      formed from ACN, and N-(2-hydroxyethyl)valine (HEVal), which is formed from EO,
      and GST genotypes were determined in blood samples obtained from 16 nonsmokers
      and 32 smokers (one to two packs/day). Smoking information was obtained by
      questionnaire, and plasma cotinine levels were determined by immunoassay.
      Glutathione transferase null genotypes (GSTM1 and GSTT1) were determined by PCR.
      Both CEVal and HEVal levels increased with increased cigarette smoking dose (both
      self-reported and cotinine-based). CEVal and HEVal levels were also correlated.
      GSTM1 and GSTT1 genotypes had little effect on CEVal concentrations. GSTM1 null
      genotypes had no significant impact on HEVal. However, HEVal levels were
      significantly elevated in GSTT1-null individuals when normalized to smoking
      status or cotinine levels. The ratio of HEVal:CEVal was also elevated in GSTT1
      null smokers (1.50 +/- 0.57 versus 0.88 +/- 0.24; P = 0.0002). The lack of a
      functional GSTT1 is estimated to increase the internal dose of EO derived from
      cigarette smoke by 50-70%.

PMID- 10919742
TI  - Mutagen sensitivity as a biomarker for second primary tumors after head and neck
      squamous cell carcinoma.
AB  - The occurrence of second primary tumors after curative treatment of early stage
      head and neck squamous cell carcinoma negatively influences the overall survival.
      Our aim was to prospectively evaluate whether mutagen sensitivity (mean number of
      chromatid breaks per cell in cultured lymphocytes exposed to bleomycin) could be
      used as a biomarker to predict which patients will develop second malignancies in
      the respiratory or upper digestive tract. Patients treated for head and neck
      squamous cell carcinoma (n = 218) were followed for approximately 6 years.
      Nineteen patients developed a second primary tumor, and each of these patients
      was matched on age, gender, cumulative smoking, tumor site, and tumor stage to
      two patients who did not develop any second malignancy. No difference between the
      groups was found with respect to mutagen sensitivity. Smoking at the time of the
      index tumor had a significant influence on the occurrence of second primary
      tumors (log-rank, P = 0.019). There was a significantly (P = 0.005) higher mean
      breaks-per-cell value in those patients who had developed their second primary
      tumor > or = 3 years after the first tumor (0.97 +/- 0.24; n = 10) compared with
      early second primary tumor patients (0.69 +/- 0.09; n = 9). Conditional on a more
      than 3-year second primary tumor-free survival (n = 38), there is a significantly
      (log-rank, P = 0.036) higher probability of a second primary tumor for mutagen
      sensitive patients [relative risk, 7.8 (95% confidence interval, 0.99-61.74; P =
      0.05)]. Mutagen sensitivity is a potential biomarker for the occurrence of 'late'
      second malignancies (> 3 years between tumors), and additional studies on the
      inclusion of this biomarker in chemoprevention trials is commendable because it
      would greatly improve their efficiency.

PMID- 10919744
TI  - Tea intake and squamous cell carcinoma of the skin: influence of type of tea
      beverages.
AB  - Differences in tea drinking habits are likely to vary by populations and could
      contribute to the inconsistencies found between studies comparing tea consumption
      and cancer risk. A population-based case-control study was used to evaluate how
      usual tea consumption patterns of an older population (n = 450) varied with
      history of squamous cell carcinoma (SCC) of the skin. A detailed tea
      questionnaire was developed to assess specific tea preparation methods and
      patterns of drinking. In this southwestern United States population, black tea
      was the predominant variety of tea consumed. We found no association between the
      broad definition of any tea consumption and skin SCC. However, the adjusted odds
      ratios (ORs) for hot and iced black tea intake were 0.63 [95% confidence interval
      (CI), 0.36-1.10] and 1.02 (95% CI, 0.64-1.63), respectively. Controls were more
      likely to report usually drinking strong hot tea (OR, 0.74; 95% CI, 0.53-1.03)
      with increased brewing time (P for trend = 0.03). Adjusting for brewing time, the
      association between skin SCC and hot black tea consumption suggests a
      significantly lower risk in consumers of hot tea compared to nonconsumers (OR,
      0.33; 95% CI, 0.12-0.87). This is one of the first studies to explore the
      relation between different types of tea consumption and occurrence of human
      cancers. Our results show that tea concentration (strength), brewing time, and
      beverage temperature have major influences on the potential protective effects of
      hot black tea in relation to skin SCC. Further studies with increased sample
      sizes are needed to evaluate the interrelationships between preparation
      techniques, tea type, and other life-style factors.

PMID- 10919745
TI  - Quantification of (7S,8R)-dihydroxy-(9R,10S)-epoxy-7,8,9,10
      tetrahydrobenzo[a]pyrene adducts in human serum albumin by laser-induced
      fluorescence: implications for the in vivo metabolism of benzo[a]pyrene.
AB  - The ubiquitous environmental carcinogen benzo[a]pyrene (BaP) is metabolized in
      vivo in humans to its ultimate carcinogenic form of 7,8-dihydroxy-9,10-epoxy
      7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). Mouse skin tumorigenicity studies
      indicate that the (7R,8S,9S,10R) enantiomer of BPDE, (7R,8S)-dihydroxy-(9S,10R)
      epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(7R,8S,9S,10R)-BPDE], is a potent tumor
      initiator, whereas the (7S,8R,9R,10S) enantiomer of BPDE, (7S,8R)-dihydroxy
      (9R,10S)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(7S,8R,9R,10S)-BPDE], may act
      as a tumor promoter. In vitro experiments have shown that human liver microsomes
      are capable of metabolizing BaP to both the (7R,8S,9S,10R) and (7S,8R,9R,10S)
      enantiomers of BPDE. However, the metabolism of BaP to (7S,8R,9R,10S)-BPDE has
      not been demonstrated in humans in vivo. The adducts formed between human serum
      albumin (HSA) and the (7S,8R,9R,10R) and (7R,8S,9S,10R) enantiomers of BPDE have
      been described previously. (7S,8R,9R,10S)-BPDE forms a stable adduct at
      histidine146 of HSA, whereas (7R,8S,9R,10R)-BPDE forms a relatively unstable
      ester adduct at aspartate187 or glutamate188 of HSA. Using high-performance
      liquid chromatography with laser-induced fluorescence (LIF) detector, we
      quantified the level of (7S,8R,9R,10S)-BPDE adducts at histidine146 in HSA
      isolated from 63 healthy males who were population control subjects for an
      ongoing case-control study of bladder cancer. By design, roughly half of the
      participants were lifelong nonsmokers (n = 35), whereas the remaining 28
      participants were current smokers of varying intensities. HP-BPDE adducts were
      detected in 60 of the 63 samples (95%) by HPLC-LIF. Adduct levels ranged from
      undetectable (<0.04 fmol/mg HSA) to 0.77 fmol/mg HSA. The samples had a mean and
      median (7S,8R,9R,10S)-BPDE-HSA adduct level of 0.22 and 0.16 fmol of adduct/mg
      albumin, respectively. Mean adduct levels did not differ between smokers and
      nonsmokers (P = 0.72). Occupational exposure to polycyclic aromatic hydrocarbons
      was unrelated to adduct level (P = 0.62). Intake frequencies of two food items
      showed statistically significant associations with adduct levels. Consumption of
      sweet potatoes was negatively related to adduct level (P = 0.029), whereas intake
      of grapefruit juice was positively related to adduct level (P = 0.045). None of
      the three indices of residential ambient air pollution under study showed a
      statistically significant association with adduct levels.

PMID- 10919746
TI  - Urinary excretion of Bowman-Birk inhibitor in humans after soy consumption as
      determined by a monoclonal antibody-based immunoassay.
AB  - The Bowman-Birk inhibitor (BBI) found in soybeans is a serine protease inhibitor
      with anticarcinogenic activity. In the present study, an ELISA for BBI was
      developed with the use of a monoclonal antibody against a reduced form of BBI.
      This newly developed ELISA method was used to measure the urinary levels of BBI
      metabolites in nine human subjects after consumption of 36-oz or 60-oz soymilk
      (containing 105 or 175 mg of BBI) at two time points 36 h apart. The results
      demonstrate that urinary BBI excretion rates peaked within 6 h and decreased to
      baseline levels within 12-24 h after soymilk ingestion. The changes in
      BBI:creatinine ratios in urine closely paralleled the changes in urinary BBI
      excretion rates after soymilk consumption. These data suggest that BBI ingested
      p.o. is absorbed and could be bioavailable for cancer chemoprevention in other
      organs in addition to those in the gastrointestinal tract.

PMID- 10919747
TI  - Lack of specificity of trans,trans-muconic acid as a benzene biomarker after
      ingestion of sorbic acid-preserved foods.
AB  - The benzene metabolite, trans,trans-muconic acid (MA), has been shown to be a
      sensitive and specific biomarker for ambient benzene exposure levels as low as
      approximately 0.5 ppm. However, at lower exposure levels, the use of MA as a
      benzene biomarker is complicated by the fact that it is also a metabolite of the
      food preservative, sorbic acid. To better assess the extent of this interference,
      MA was measured in sequential spot urine samples over a 2-day study period from
      eight volunteers (four adults and two parent-children pairs) who consumed two
      sorbic acid-preserved foods. Large increases in MA concentration were seen after
      ingestion of both foods. Individual peaks ranged as high as 1673.7 ng/ml (705.3
      ng/mg creatinine) in adults and 1752.1 ng/mg creatinine (1221.3 ng/ml) in
      children. Ratios of peak to baseline values varied from 2.5 to 60. The average
      peak in the seven subjects who showed an increase in MA after ingestion of the
      first sorbic acid-containing food was 531.1 ng/ml (693.2 ng/mg creatinine). The
      average in the seven participants who ingested the second food was 1102.1 ng/ml
      (795.3 ng/mg creatinine). Twenty-four-hour personal air benzene levels were all
      low (< or = 5.6 ppb). Substantial variation in MA results were seen in some males
      related to creatinine adjustment. These data indicate that sorbic acid-preserved
      foods have the potential to cause substantial interference with MA as a biomarker
      for both occupational and environmental benzene exposure in populations, such as
      in the United States, where consumption of preserved foods is common. Development
      of methods to minimize and/or assess sorbic acid interference will improve MA
      specificity in such populations.

PMID- 10919748
TI  - Heredity and risk of cancer of the esophagus and gastric cardia.
AB  - The importance of genetic factors in the etiology of esophageal cancer is
      uncertain. We addressed the question of heredity in a population-based,
      nationwide case-control study conducted in Sweden during 1995 through 1997. The
      study involved 189 patients with esophageal adenocarcinoma, 262 with cardia
      adenocarcinoma, 167 with esophageal squamous cell carcinoma, and, for comparison,
      820 control subjects. Familial occurrence of cancer was explored at face-to-face
      interviews. Logistic regression, with multivariate adjustment for potential
      confounders, was used to calculate odds ratios (ORs), which estimated relative
      risk. Occurrence of esophageal cancer among first-degree relatives did not
      increase the risk of adenocarcinoma or squamous cell carcinoma of the esophagus.
      Neither were there any significant associations with familial occurrence of
      gastric cancer or other gastrointestinal tumors. The risk of cardia
      adenocarcinoma was moderately increased among persons with first-degree relatives
      with gastric cancer (OR, 1.6; 95% confidence interval, 1.0-2.6). Familial
      occurrence of any cancer was not associated with increased risks of any of the
      three studied tumors. In conclusion, heredity does not seem to contribute
      importantly to the occurrence of esophageal cancer of any histological type. A
      weak association between familial gastric cancer and the risk of cardia cancer
      may represent a genetic link.

PMID- 10919749
TI  - The risk of cervical cancer in relation to serum concentrations of folate,
      vitamin B12, and homocysteine.
AB  - Due to its role in the synthesis and repair of DNA, folate may protect against
      the development of cervical cancer. Prospective data on the possible association
      between folate and cervical cancer have been lacking. There is also a paucity of
      prospective evidence concerning the possible associations between cervical cancer
      and vitamin B12, which shares pathways with folate, and homocysteine, a marker of
      low B vitamin concentrations. A nested case-control study was conducted to
      prospectively evaluate the associations between cervical cancer and serum
      concentrations of folate, vitamin B12, and homocysteine. Among a community-based
      cohort of women who donated blood in 1974 for a serum bank in Washington County,
      Maryland, 39 cases of cervical cancer diagnosed between 1975 and mid-1990 were
      included in the study (13 cases of invasive cervical cancer and 26 cases of
      carcinoma in situ). Two controls were matched to each case by age, race, and sex.
      Stored serum from the cases and controls was assayed for folate, B12, and
      homocysteine concentrations. For folate, adjusted odds ratios were 1.0, 0.62, and
      0.60 for the low to high thirds of the serum concentrations, respectively, a
      trend in the protective direction that was not statistically significant (P for
      trend = 0.42). Overall, the results for vitamin B12 tended to mimic those for
      folate, whereas the associations for homocysteine tended to be in the opposite
      direction. None of the results of this study were statistically significant, but
      patterns of the associations are in accord with hypothesized mechanistic pathways
      concerning B vitamins and cervical cancer.

PMID- 10919750
TI  - How accurately does the medical record capture maternal history of cancer?
AB  - We sought to assess the reliability of information regarding the maternal history
      of cancer by comparing the medical records of 214 women with breast cancer, ages
      26-59 years and diagnosed in 1974-1995, and of their controls with the medical
      records of their mothers. Subjects were members of Kaiser Permanente, Northern
      California, selected for a study of early-life predictors of breast cancer. For
      any type of cancer identified in the mother's medical record, the proportion
      noted in the daughter's medical record at least 6 months before the daughter's
      diagnosis or reference date was 56% among cases and 32% among controls. The odds
      ratio for the association of maternal cancer history with breast cancer risk was
      2.1 using the maternal record and 3.5 using the subject's record. For a maternal
      history of breast cancer, the proportion noted in the subject's record was 79%
      among cases and 57% among controls, and the odds ratios were 4.0 and 6.5,
      respectively. We believe that the case-control difference in missing information
      was attributable to higher utilization of breast cancer screening among cases.
      This study illustrates the need to assess the impact of screening differences on
      the ascertainment of information from the medical records.

PMID- 10919751
TI  - Calcific small vessel ischemic disease (calciphylaxis) in dialysis patients.

PMID- 10919752
TI  - Biocompatibility and functional performance of a polyethylene glycol acid-grafted
      cellulosic membrane for hemodialysis.
AB  - In order to improve the biochemical reactivity of the cellulose polymer, which is
      mainly attributed to the presence of surface hydroxyl groups, derivatized
      cellulosic membranes have been engineered replacing or masking some or all of the
      hydroxyl groups in the manufacturing process of the membrane. The present study
      was set up to analyze both biocompatibility and functional performance of two
      different derivatized cellulosic membranes (cellulose diacetate; polyethylene
      glycol, PEG, acid-grafted cellulose) as compared to a synthetic membrane
      (polymethylmethacrylate, PMMA). Cellulose diacetate is prepared by substituting
      hydroxyl groups with acetyl groups; PEG cellulose is obtained by grafting PEG
      chains onto the cellulosic polymer with a smaller amount of substitution than
      cellulose diacetate. While the three dialyzers provided similar urea and
      creatinine removal, the dialyzer containing cellulose diacetate showed a reduced
      ability to remove 32-microglobulin compared to that containing PEG cellulose or
      PMMA. A transient reduction in leukocyte count was observed for both derivatized
      cellulosic membranes. The neutrophil and monocyte counts throughout the entire
      dialysis session showed a closer parallelism with the cellular expression of the
      adhesive receptor CD 15s (sialyl-Lewis x molecule) than with CD11b/CD18
      expression. Platelet activation, as indicated by the percentage of cells
      expressing the activation markers CD62P (P-selectin) and CD63 (gp53), occurred
      with all membranes at 15 min of dialysis and also with PMMA at 30 min. An
      increased formation of platelet-neutrophil and platelet-monocyte coaggregates was
      found at 15 and 30 min during dialysis with cellulose diacetate and PMMA but not
      with PEG cellulose. Generally in concomitance with the increase in platelet
      neutrophil coaggregates, an increased hydrogen peroxide production by neutrophils
      occurred. Our results indicate that derivatizing cellulose may represent a useful
      approach to improve the biocompatibility of the cellulose polymer, though some
      homeostatic reactions remain activated. Our results also indicate that there may
      be a great variability in the biocompatibility profile of derivatize cellulosic
      membranes which most likely stem from the different type of structural
      modification rather than from the degree of hydroxyl group replacement.

PMID- 10919753
TI  - Clinical characterisation of polysulfone LS membrane for renal replacement
      therapy.
AB  - The solute transport characteristics and biocompatibility of a new polysulfone
      membrane (Polysulfone LS, Fresenius Medical Care, Bad Homburg, Germany) has been
      established and compared for two different sizes of dialyser (1.3 and 1.8 m2).
      The in vivo small molecular clearance of the two sizes of dialyser showed an
      overlap in performance. Neutropenia was slight and independent of the membrane
      area as were changes in C5adesArg. The membrane induced neutrophil degranulation
      characterised by the release of elestase alpha1 inhibitor complex with time
      averaged values over 180 minutes related to membrane area (p=0.010). Heparin
      activity during dialysis with the membrane was within the therapeutic range
      necessary for anticoagulation (0.3-1.0 IU/ml), but despite this an increase in
      thrombin antithrombin 111 levels during treatment was noted. Polysulfone LS
      extends the range of polysulfone membranes available for clinical use and its
      performance is such that it may be considered as a membrane for the treatment of
      patients awaiting a transplant, or in whom use of the high flux therapies may be
      inappropriate.

PMID- 10919754
TI  - ARDS in fulminant ornithosis and treatment with extracorporeal lung assist.
AB  - We report a 47-year-old male patient with fulminant ornithosis who developed
      severe respiratory failure leading to acute respiratory distress syndrome (ARDS)
      complicated by gastrointestinal, neurological and renal symptoms. ARDS was
      successfully treated by extracorporeal lung assist. As leukocytosis is typically
      absent in ornithosis, C-reactive protein, interleukin 6 and procalcitonin were
      used as infection parameters in order to monitor clinical development. The
      English-language literature on severe cases of ornithosis requiring respiratory
      support over the past 30 years is reviewed.

PMID- 10919755
TI  - Effect of hemodiabsorption and sorbent-based pheresis on amino acid levels in
      hepatic failure.
AB  - Changes in plasma amino acid concentrations were measured in patients with
      hepatic failure during extracorporeal hemodiabsorption (using the Liver Dialysis
      Unit, "the Unit") or hemodiabsorption plus sorbent-based pheresis treatment
      (using the Liver Dialysis Plasmafilter Unit, "the PF-Unit") Systems. Eight
      patients with hepatic failure, grade 3 or 4 encephalopathy, elevated bilirubin
      and/or creatinine levels and respiratory or renal failure were treated for 1-3
      days with the Unit alone. Three of these were also treated with the Unit
      containing 10 g of BCAA in the sorbent suspension. Four patients with hepatic
      failure treated with the PF Unit also had 10 g of branched chain amino acid
      (BCAA) added to the sorbents of the Unit portion of this device. Pre- and post
      plasma samples were drawn and high performance liquid chromatography (HPLC) was
      used to separate and detect amino acids in the plasma. Both the Unit and the PF
      Unit have the capability to selectively remove various amino acids, especially
      aromatic amino acids (AAA). The pre-treatment amino acid profiles of plasma were
      typical for hepatic failure, with abnormally high levels of phenylalanine,
      tyrosine, tryptophan, and methionine and decreased levels of valine, leucine and
      isbolucine. The average pre-treatment Fischer ratio (BCAA/AAA) for both Unit and
      PF-Unit patients was 1.43 (+/- 0.58). Treatments by both systems resulted in an
      increase of BCAA levels in blood and concomitant decrease of AAA levels, with an
      average Fischer ratio improvement of 30-38% for the Unit and PF-Unit without
      BCAA. The Fischer ratio improved by 90% (average) for the Unit with BCAA. Levels
      of many other amino acids (such as alanine, glycine, proline or lysine) increased
      during both Unit and PF-Unit treatments. The removal of strongly protein-bound
      toxin and amino acids such as tryptophan and sulphydryl amino acids was more
      effective by the PF-Unit. Both the Unit and the PF-Unit have the unique
      capability to remove toxic aromatic amino acids while increasing BCAA levels in
      patient. The increase in many amino acid levels may be related to the removal of
      toxins that interfere with normal amino acid metabolism. The addition of the PF
      module improves the removal of bilirubin and similarly protein-bound chemicals.
      Changes in amino acid profiles by the Unit and the PF-Unit contrast markedly with
      other extracorporeal devices.

PMID- 10919756
TI  - Development of a hybrid artificial liver using a polyurethane foam/hepatocyte
      spheroid packed-bed module.
AB  - Primary dog hepatocytes spontaneously formed spheroids in the pores of
      polyurethane foam (PUF) within 1-2 days of stationary culture. The spheroids,
      about 100-150 microm in diameter, partly attached to the surface and immobilized
      inside these pores. The lidocaine disappearance rate decreased to about 4
      microg/10(5) viable cells/day for 10 days, while in the PUF/spheroid culture the
      rate was maintained at almost the initial level of 8 microg/10(5) viable
      cells/day for 10 days. Then, two scales of PUF packed-bed modules were designed.
      A small module (PUF volume; 14.5 cm3) was used for in vitro culture to
      investigate optimum culture conditions, and a large module (PUF volume; 300 cm3)
      was designed for dog experiments. Hepatocytes inoculated in these modules also
      formed spheroids and maintained almost the same activity of albumin secretion
      rate (111 microg/cm3 PUF/day in the small module and 87.7 microg/cm3 PUF/day in
      the large module). These results indicate that the PUF packed-bed module
      containing hepatocyte-spheroids is promising as a hybrid artificial liver.

PMID- 10919757
TI  - Quantitative and qualitative evaluation of blood salvaged after extracorporeal
      circulation (ECC) in paediatric heart surgery. Study of biochemical,
      morphological and structural variations of RBC after ECC and after salvaging of
      ECC circuit priming blood.
AB  - The salvaging of ECC circuit priming blood is essential for reducing the
      morbidity related to homologous blood transfusions and the importance of this
      technique is inversely proportionate to the age and weight of the child. In
      infants, the washing and centrifugation of blood not only drastically reduce the
      risk of contracting blood-transmitted diseases and cut management costs, but are
      also of considerable hemodynamic importance, producing a rapid normalization of
      the patient's hematocrit and hemoglobin and balancing the O2 consumption/demand
      ratio. The marketing of miniaturized salvagin devices with 55 ml bowls by Dideco
      has made possible the recovery of small quantities of blood, so as to normalise
      the hematic crisis and permit the application of total hemodilution in low-weight
      patients. The salvaged blood shows an average hematocrit of 52.7+/-9.7% (max
      68.1%) and an average hemoglobin of 17.6 +/- 2.9 g/dl (max 20.7 g/dl), and
      maintains its structural components, osmotic resistance, concentration of
      intraerythrocytic hemoglobin and mean corpuscular hemoglobin all intact. Washing
      with isoosmotic and isoionic hydroelectrolytic solutions normalizes the ionic
      situation in the post-operative period and activated blood salvaging after
      Extracorporeal Circulation. The use of solutions without nutritional substances
      results however in a considerable fall in the number of enzymes in the
      intraerythrocytic metabolic glucide chain (G6PDH: -40.7 +/- 14.3% p<0.001), (PK: 
      23.8 +/- 20.5% p<0.03). This drop may be responsible for erythrocytic
      morphological alterations (echinocytic change) and probably for the release of
      hemoglobin from the red blood cells. Washing with isoionic, isoosmotic solutions
      containing G5% and adenine could, at least in theory, improve the quality of the
      salvaged blood, by normalizing the morphology and the volume of the RBC and by
      increasing the hematocrit.

PMID- 10919758
TI  - Prolonged response of chronic immune thrombocytopenic purpura (ITP) to
      extracorporeal immunoadsorption.

PMID- 10919760
TI  - Diversity of thiosulfate-oxidizing bacteria from marine sediments and
      hydrothermal vents.
AB  - Species diversity, phylogenetic affiliations, and environmental occurrence
      patterns of thiosulfate-oxidizing marine bacteria were investigated by using new
      isolates from serially diluted continental slope and deep-sea abyssal plain
      sediments collected off the coast of New England and strains cultured previously
      from Galapagos hydrothermal vent samples. The most frequently obtained new
      isolates, mostly from 10(3)- and 10(4)-fold dilutions of the continental slope
      sediment, oxidized thiosulfate to sulfate and fell into a distinct phylogenetic
      cluster of marine alpha-Proteobacteria. Phylogenetically and physiologically,
      these sediment strains resembled the sulfate-producing thiosulfate oxidizers from
      the Galapagos hydrothermal vents while showing habitat-related differences in
      growth temperature, rate and extent of thiosulfate utilization, and carbon
      substrate patterns. The abyssal deep-sea sediments yielded predominantly base
      producing thiosulfate-oxidizing isolates related to Antarctic marine
      Psychroflexus species and other cold-water marine strains of the Cytophaga
      Flavobacterium-Bacteroides phylum, in addition to gamma-proteobacterial isolates
      of the genera Pseudoalteromonas and Halomonas-Deleya. Bacterial thiosulfate
      oxidation is found in a wide phylogenetic spectrum of Flavobacteria and
      Proteobacteria.

PMID- 10919762
TI  - Controlling instability in gacS-gacA regulatory genes during inoculant production
      of Pseudomonas fluorescens biocontrol strains.
AB  - Secondary metabolism in fluorescent pseudomonads is globally regulated by gacS,
      which encodes a membrane-bound sensor kinase, and gacA, which encodes a
      transcriptional response regulator. Spontaneous mutation in either gene blocked
      biosynthesis of the antimicrobial compounds hydrogen cyanide, 2,4
      diacetylphloroglucinol, pyoluteorin, and pyrrolnitrin by the model biocontrol
      strain Pseudomonas fluorescens CHA0. Spontaneous mutants also had altered
      abilities to utilize several carbon sources and to increase medium pH compared
      with the wild type, suggesting that gacS and gacA influence primary as well as
      secondary bacterial metabolism. Inoculant efficacy for biocontrol was
      significantly reduced by contamination with regulatory mutants which accumulated
      during inoculum production. Spontaneous mutants accumulated in all 192 separate
      liquid cultures examined, typically at a frequency of 1% or higher after 12 days.
      During scale-up in a simulated industrial fermentation process, mutants increased
      exponentially and accounted for 7, 23, and 61% of the total viable cells after
      transfer to 20-, 100-, and 500-ml preparations, respectively. GacS(-) and GacA(-)
      mutants had identical phenotypes and occurred at the same frequency, indicating
      that the selective pressures for the two mutants were similar. We developed a
      simple screening method for monitoring inoculant quality based on the distinctive
      appearance of mutant colonies (i.e., orange color, enlarged diameter,
      hyperfluorescence). Mutant competitiveness was favored in a nutrient-rich medium
      with a high electrolyte concentration (nutrient broth containing yeast extract).
      We were able to control mutant accumulation and to clean up contaminated cultures
      by using certain mineral amendments (i.e., zinc, copper, cobalt, manganese, and
      ammonium molybdate) or by diluting media 1/10. Spontaneous mutants and genetic
      constructs had the same response to culture conditions. Zinc and medium dilution
      were also effective for improving the genetic stability of other P. fluorescens
      biocontrol strains obtained from Ghana and Italy.

PMID- 10919761
TI  - Characterization of S-triazine herbicide metabolism by a Nocardioides sp.
      isolated from agricultural soils.
AB  - Atrazine, a herbicide widely used in corn production, is a frequently detected
      groundwater contaminant. Nine gram-positive bacterial strains able to use this
      herbicide as a sole source of nitrogen were isolated from four farms in central
      Canada. The strains were divided into two groups based on repetitive extragenic
      palindromic (rep)-PCR genomic fingerprinting with ERIC and BOXA1R primers. Based
      on 16S ribosomal DNA sequence analysis, both groups were identified as
      Nocardioides sp. strains. None of the isolates mineralized [ring-U
      (14)C]atrazine. There was no hybridization to genomic DNA from these strains
      using atzABC cloned from Pseudomonas sp. strain ADP or trzA cloned from
      Rhodococcus corallinus. S-Triazine degradation was studied in detail in
      Nocardioides sp. strain C190. Oxygen was not required for atrazine degradation by
      whole cells or cell extracts. Based on high-pressure liquid chromatography and
      mass spectrometric analyses of products formed from atrazine in incubations of
      whole cells with H(2)(18)O, sequential hydrolytic reactions converted atrazine to
      hydroxyatrazine and then to the end product N-ethylammelide. Isopropylamine, the
      putative product of the second hydrolytic reaction, supported growth as the sole
      carbon and nitrogen source. The triazine hydrolase from strain C190 was isolated
      and purified and found to have a K(m) for atrazine of 25 microM and a V(max) of
      31 micromol/min/mg of protein. The subunit molecular mass of the protein was 52
      kDa. Atrazine hydrolysis was not inhibited by 500 microM EDTA but was inhibited
      by 100 microM Mg, Cu, Co, or Zn. Whole cells and purified triazine hydrolase
      converted a range of chlorine or methylthio-substituted herbicides to the
      corresponding hydroxy derivatives. In summary, an atrazine-metabolizing
      Nocardioides sp. widely distributed in agricultural soils degrades a range of s
      triazine herbicides by means of a novel s-triazine hydrolase.

PMID- 10919763
TI  - Engineering of the pyruvate dehydrogenase bypass in Saccharomyces cerevisiae:
      role of the cytosolic Mg(2+) and mitochondrial K(+) acetaldehyde dehydrogenases
      Ald6p and Ald4p in acetate formation during alcoholic fermentation.
AB  - Acetic acid plays a crucial role in the organoleptic balance of many fermented
      products. We have investigated the factors controlling the production of acetate
      by Saccharomyces cerevisiae during alcoholic fermentation by metabolic
      engineering of the enzymatic steps involved in its formation and its utilization.
      The impact of reduced pyruvate decarboxylase (PDC), limited acetaldehyde
      dehydrogenase (ACDH), or increased acetoacetyl coenzyme A synthetase (ACS) levels
      in a strain derived from a wine yeast strain was studied during alcoholic
      fermentation. In the strain with the PDC1 gene deleted exhibiting 25% of the PDC
      activity of the wild type, no significant differences were observed in the
      acetate yield or in the amounts of secondary metabolites formed. A strain
      overexpressing ACS2 and displaying a four- to sevenfold increase in ACS activity
      did not produce reduced acetate levels. In contrast, strains with one or two
      disrupted copies of ALD6, encoding the cytosolic Mg(2+)-activated NADP-dependent
      ACDH and exhibiting 60 and 30% of wild-type ACDH activity, showed a substantial
      decrease in acetate yield (the acetate production was 75 and 40% of wild-type
      production, respectively). This decrease was associated with a rerouting of
      carbon flux towards the formation of glycerol, succinate, and butanediol. The
      deletion of ALD4, encoding the mitochondrial K(+)-activated NAD(P)-linked ACDH,
      had no effect on the amount of acetate formed. In contrast, a strain lacking both
      Ald6p and Ald4p exhibited a long delay in growth and acetate production,
      suggesting that Ald4p can partially replace the Ald6p isoform. Moreover, the ald6
      ald4 double mutant was still able to ferment large amounts of sugar and to
      produce acetate, suggesting the contribution of another member(s) of the ALD
      family.

PMID- 10919764
TI  - Effect of starvation and the viable-but-nonculturable state on green fluorescent
      protein (GFP) fluorescence in GFP-tagged Pseudomonas fluorescens A506.
AB  - The green fluorescent protein (GFP) gene, gfp, of the jellyfish Aequorea victoria
      is being used as a reporter system for gene expression and as a marker for
      tracking prokaryotes and eukaryotes. Cells that have been genetically altered
      with the gfp gene produce a protein that fluoresces when it is excited by UV
      light. This unique phenotype allows gfp-tagged cells to be specifically monitored
      by nondestructive means. In this study we determined whether a gfp-tagged strain
      of Pseudomonas fluorescens continued to fluoresce under conditions under which
      the cells were starved, viable but nonculturable (VBNC), or dead. Epifluorescent
      microscopy, flow cytometry, and spectrofluorometry were used to measure
      fluorescence intensity in starved, VBNC, and dead or dying cells. Results
      obtained by using flow cytometry indicated that microcosms containing VBNC cells,
      which were obtained by incubation under stress conditions (starvation at 37.5
      degrees C), fluoresced at an intensity that was at least 80% of the intensity of
      nonstressed cultures. Similarly, microcosms containing starved cells incubated at
      5 and 30 degrees C had fluorescence intensities that were 90 to 110% of the
      intensity of nonstressed cells. VBNC cells remained fluorescent during the entire
      6-month incubation period. In addition, cells starved at 5 or 30 degrees C
      remained fluorescent for at least 11 months. Treatment of the cells with UV light
      or incubation at 39 or 50 degrees C resulted in a loss of GFP from the cells.
      There was a strong correlation between cell death and leakage of GFP from the
      cells, although the extent of leakage varied depending on the treatment. Most
      dead cells were not GFP fluorescent, but a small proportion of the dead cells
      retained some GFP at a lower concentration than the concentration in live cells.
      Our results suggest that gfp-tagged cells remain fluorescent following starvation
      and entry into the VBNC state but that fluorescence is lost when the cells die,
      presumably because membrane integrity is lost.

PMID- 10919765
TI  - Simple and efficient method for heterologous expression of clostridial proteins.
AB  - Many clostridial proteins are poorly produced in Escherichia coli. It has been
      suggested that this phenomena is due to the fact that several types of codons
      common in clostridial coding sequences are rarely used in E. coli and the
      quantities of the corresponding tRNAs in E. coli are not sufficient to ensure
      efficient translation of the corresponding clostridial sequences. To address this
      issue, we amplified three E. coli genes, ileX, argU, and leuW, in E. coli; these
      genes encode tRNAs that are rarely used in E. coli (the tRNAs for the ATA, AGA,
      and CTA codons, respectively). Our data demonstrate that amplification of ileX
      dramatically increased the level of production of most of the clostridial
      proteins tested, while amplification of argU had a moderate effect and
      amplification of leuW had no effect. Thus, amplification of certain tRNA genes
      for rare codons in E. coli improves the expression of clostridial genes in E.
      coli, while amplification of other tRNAs for rare codons might not be needed for
      improved expression. We also show that amplification of a particular tRNA gene
      might have different effects on the level of protein production depending on the
      prevalence and relative positions of the corresponding codons in the coding
      sequence. Finally, we describe a novel approach for improving expression of
      recombinant clostridial proteins that are usually expressed at a very low level
      in E. coli.

PMID- 10919766
TI  - Requirement of autolytic activity for bacteriocin-induced lysis.
AB  - The bacteriocin produced by Lactococcus lactis IFPL105 is bactericidal against
      several Lactococcus and Lactobacillus strains. Addition of the bacteriocin to
      exponential-growth-phase cells resulted in all cases in bacteriolysis. The
      bacteriolytic response of the strains was not related to differences in
      sensitivity to the bacteriocin and was strongly reduced in the presence of
      autolysin inhibitors (Co(2+) and sodium dodecyl sulfate). When L. lactis MG1363
      and its derivative deficient in the production of the major autolysin AcmA
      (MG1363acmADelta1) were incubated with the bacteriocin, the latter did not lyse
      and no intracellular proteins were released into the medium. Incubation of cell
      wall fragments of L. lactis MG1363, or of L. lactis MG1363acmADelta1 to which
      extracellular AcmA was added, in the presence or absence of the bacteriocin had
      no effect on the speed of cell wall degradation. This result indicates that the
      bacteriocin does not degrade cell walls, nor does it directly activate the
      autolysin AcmA. The autolysin was also responsible for the observed lysis of L.
      lactis MG1363 cells during incubation with nisin or the mixture of lactococcins
      A, B, and M. The results presented here show that lysis of L. lactis after
      addition of the bacteriocins is caused by the resulting cell damage, which
      promotes uncontrolled degradation of the cell walls by AcmA.

PMID- 10919767
TI  - Identification of the dimerization domain of dehalogenase IVa of Burkholderia
      cepacia MBA4.
AB  - Haloacid dehalogenases are enzymes that catalyze the hydrolytic removal of
      halogens from haloalkanoic acids. Dehalogenase IVa (DehIVa) from Burkholderia
      cepacia MBA4 and dehalogenase CI (DehCI) from Pseudomonas sp. strain CBS3 exhibit
      68% identity. Despite their similarity DehIVa is a dimeric enzyme while DehCI is
      a monomer. In this work, we describe the identification of the domain that
      confers the dimerization function of DehIVa. Recombinant DNA molecules were
      constructed by fusion of the respective dehalogenase genes hdlIVa and dehCI. When
      amino acids 73 to 89 of DehCI were replaced by amino acids 74 to 90 of DehIVa,
      the recombinant molecule migrated like that of DehIVa in a nondenaturing activity
      stained gel. Similarly, when residues 73 to 89 of DehIVa were replaced by the
      corresponding residues of DehCI, the chimera migrated as a monomer. These 17
      amino acid changes were able to determine the aggregation states of the
      molecules. The retention of the catalytic function in these chimeras indicated
      that the overall folding of these proteins was not affected. Site-directed
      mutagenesis on hdlIVa however indicated that amino acids Phe58, Thr65, Leu78, and
      Phe92 of DehIVa are also important for the aggregation state of the protein. This
      indicates that the 17 residues are not sufficient for the dimerization of the
      protein.

PMID- 10919768
TI  - Common degradative pathways of morpholine, thiomorpholine, and piperidine by
      Mycobacterium aurum MO1: evidence from (1)H-nuclear magnetic resonance and
      ionspray mass spectrometry performed directly on the incubation medium.
AB  - In order to see if the biodegradative pathways for morpholine and thiomorpholine
      during degradation by Mycobacterium aurum MO1 could be generalized to other
      heterocyclic compounds, the degradation of piperidine by this strain was
      investigated by performing (1)H-nuclear magnetic resonance directly with the
      incubation medium. Ionspray mass spectrometry, performed without purification of
      the samples, was also used to confirm the structure of some metabolites during
      morpholine and thiomorpholine degradation. The results obtained with these two
      techniques suggested a general pathway for degradation of nitrogen heterocyclic
      compounds by M. aurum MO1. The first step of the degradative pathway is cleavage
      of the C---N bond; this leads formation of an intermediary amino acid, which is
      followed by deamination and oxidation of this amino acid into a diacid. Except in
      the case of thiodiglycolate obtained from thiomorpholine degradation, the
      dicarboxylates are completely mineralized by the bacterial cells. A comparison
      with previously published data showed that this pathway could be a general
      pathway for degradation by other strains of members of the genus Mycobacterium.

PMID- 10919769
TI  - Fungal colonization and biodeterioration of plasticized polyvinyl chloride.
AB  - Significant substratum damage can occur when plasticized PVC (pPVC) is colonized
      by microorganisms. We investigated microbial colonization of pPVC in an in situ,
      longitudinal study. Pieces of pPVC containing the plasticizers dioctyl phthalate
      and dioctyl adipate (DOA) were exposed to the atmosphere for up to 2 years.
      Fungal and bacterial populations were quantified, and colonizing fungi were
      identified by rRNA gene sequencing and morphological characteristics.
      Aureobasidium pullulans was the principal colonizing fungus, establishing itself
      on the pPVC between 25 and 40 weeks of exposure. A group of yeasts and yeast-like
      fungi, including Rhodotorula aurantiaca and Kluyveromyces spp., established
      themselves on the pPVC much later (after 80 weeks of exposure). Numerically,
      these organisms dominated A. pullulans after 95 weeks, with a mean viable count
      +/- standard error of 1,000 +/- 200 yeast CFU cm(-2), compared to 390 +/- 50 A.
      pullulans CFU cm(-2). No bacterial colonization was observed. We also used in
      vitro tests to characterize the deteriogenic properties of fungi isolated from
      the pPVC. All strains of A. pullulans tested could grow with the intact pPVC
      formulation as the sole source of carbon, degrade the plasticizer DOA, produce
      extracellular esterase, and cause weight loss of the substratum during growth in
      vitro. In contrast, several yeast isolates could not grow on pPVC or degrade DOA.
      These results suggest that microbial succession may occur during the colonization
      of pPVC and that A. pullulans is critical to the establishment of a microbial
      community on pPVC.

PMID- 10919770
TI  - Molecular cloning, sequencing, and expression in Escherichia coli of the gene
      encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from Alcaligenes
      faecalis N-38A.
AB  - The gene encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from
      Alcaligenes faecalis N-38A was cloned and characterized. The coding region of
      this gene is 1,299 bp long. The predicted primary protein is composed of 433
      amino acid residues, with a 31-amino-acid signal peptide. The mature protein is
      composed of 402 amino acid residues with a molecular mass of 46,163 Da. The
      derived amino acid sequence of the enzyme showed no significant sequence
      similarity to any other proteins reported so far. The 5-oxoprolinase gene was
      expressed in Escherichia coli by using a regulatory expression system with an
      isopropyl-beta-D-thiogalactopyranoside-inducible tac promoter, and its expression
      level was approximately 16 mg per liter. The purified enzyme has the same
      characteristics as the authentic enzyme, except for the amino terminus, which has
      three additional amino acids. The enzyme was markedly inhibited by p
      chloromercuribenzoic acid, EDTA, o-phenanthroline, HgCl(2), and CuSO(4). The EDTA
      inactivated enzyme was completely restored by the addition of Zn(2+) or Co(2+).
      In addition, the enzyme was found to contain 1 g-atom of zinc per mol of protein.
      These results suggest that the 5-oxoprolinase produced by A. faecalis N-38A is a
      zinc metalloenzyme.

PMID- 10919771
TI  - Identification of Mycobacterium ulcerans in the environment from regions in
      Southeast Australia in which it is endemic with sequence capture-PCR.
AB  - We recently described the use of PCR to identify the environmental source of
      Mycobacterium ulcerans during an outbreak of ulcerative disease that occurred in
      a localized region of southeast Australia. The PCR used was based on
      amplification of the M. ulcerans-specific insertion sequence, IS2404. In this
      study we developed a new test that is a substantial improvement over the original
      PCR method in terms of sensitivity, reliability, and ease of use. In the new
      method magnetic bead sequence capture-PCR is used to detect two M. ulcerans
      sequences (IS2404 and IS2606) and total mycobacterial 16S ribosomal DNA. We used
      sequence capture-PCR to test water and plant material collected over a 12-month
      period during 1998 and 1999 from sites near the centers of two distinct foci of
      M. ulcerans infections. A golf course irrigation system in one area and a small
      shallow lake in another area repeatedly were PCR positive for M. ulcerans. Nearby
      sites and sites unrelated to the endemic areas were negative. Based on the PCR
      data, a most-probable-number method was used to estimate the concentration of M.
      ulcerans cells in positive samples from both regions. This procedure resulted in
      average concentrations of 0.5 cell per 100 ml of water and 40 cells per 100 g of
      detritus. Loss of the PCR signal coincided with a decrease in ulcerative disease
      in each area. These results provide further evidence that M. ulcerans may be
      transmitted from a point environmental source and demonstrate the utility of
      magnetic bead sequence capture-PCR for identification of nonculturable microbial
      pathogens in the environment.

PMID- 10919772
TI  - Microbial life beneath a high arctic glacier.
AB  - The debris-rich basal ice layers of a high Arctic glacier were shown to contain
      metabolically diverse microbes that could be cultured oligotrophically at low
      temperatures (0.3 to 4 degrees C). These organisms included aerobic
      chemoheterotrophs and anaerobic nitrate reducers, sulfate reducers, and
      methanogens. Colonies purified from subglacial samples at 4 degrees C appeared to
      be predominantly psychrophilic. Aerobic chemoheterotrophs were metabolically
      active in unfrozen basal sediments when they were cultured at 0.3 degrees C in
      the dark (to simulate nearly in situ conditions), producing (14)CO(2) from
      radiolabeled sodium acetate with minimal organic amendment (> or =38 microM C).
      In contrast, no activity was observed when samples were cultured at subfreezing
      temperatures (< or =-1.8 degrees C) for 66 days. Electron microscopy of thawed
      basal ice samples revealed various cell morphologies, including dividing cells.
      This suggests that the subglacial environment beneath a polythermal glacier
      provides a viable habitat for life and that microbes may be widespread where the
      basal ice is temperate and water is present at the base of the glacier and where
      organic carbon from glacially overridden soils is present. Our observations raise
      the possibility that in situ microbial production of CO(2) and CH(4) beneath ice
      masses (e.g., the Northern Hemisphere ice sheets) is an important factor in
      carbon cycling during glacial periods. Moreover, this terrestrial environment may
      provide a model for viable habitats for life on Mars, since similar conditions
      may exist or may have existed in the basal sediments beneath the Martian north
      polar ice cap.

PMID- 10919773
TI  - Purification and biochemical characterization of mutacin I from the group I
      strain of Streptococcus mutans, CH43, and genetic analysis of mutacin I
      biosynthesis genes.
AB  - Previously, we reported isolation and characterization of mutacin III and genetic
      analysis of mutacin III biosynthesis genes from the group III strain of
      Streptococcus mutans, UA787 (F. Qi, P. Chen, and P. W. Caufield, Appl. Environ.
      Microbiol. 65:3880-3887, 1999). During the same process of isolating the mutacin
      III structural gene, we also cloned the structural gene for mutacin I. In this
      report, we present purification and biochemical characterization of mutacin I
      from the group I strain CH43 and compare mutacin I and mutacin III biosynthesis
      genes. The mutacin I biosynthesis gene locus consists of 14 genes in the order
      mutR, -A, -A', -B, -C, -D, -P, -T, -F, -E, -G, orfX, orfY, orfZ. mutA is the
      structural gene for mutacin I, while mutA' is not required for mutacin I
      activity. DNA and protein sequence analysis revealed that mutacins I and III are
      homologous to each other, possibly arising from a common ancestor. The mature
      mutacin I is 24 amino acids in size and has a molecular mass of 2, 364 Da.
      Ethanethiol modification and peptide sequencing of mutacin I revealed that it
      contains six dehydrated serines, four of which are probably involved with
      thioether bridge formation. Comparison of the primary sequence of mutacin I with
      that of mutacin III and epidermin suggests that mutacin I likely has the same
      bridging pattern as epidermin.

PMID- 10919774
TI  - Metabolic activity of permafrost bacteria below the freezing point.
AB  - Metabolic activity was measured in the laboratory at temperatures between 5 and 
      20 degrees C on the basis of incorporation of (14)C-labeled acetate into lipids
      by samples of a natural population of bacteria from Siberian permafrost
      (permanently frozen soil). Incorporation followed a sigmoidal pattern similar to
      growth curves. At all temperatures, the log phase was followed, within 200 to 350
      days, by a stationary phase, which was monitored until the 550th day of activity.
      The minimum doubling times ranged from 1 day (5 degrees C) to 20 days (-10
      degrees C) to ca. 160 days (-20 degrees C). The curves reached the stationary
      phase at different levels, depending on the incubation temperature. We suggest
      that the stationary phase, which is generally considered to be reached when the
      availability of nutrients becomes limiting, was brought on under our conditions
      by the formation of diffusion barriers in the thin layers of unfrozen water known
      to be present in permafrost soils, the thickness of which depends on temperature.

PMID- 10919776
TI  - Three-year study to assess human enteric viruses in shellfish.
AB  - The main pathogenic enteric viruses able to persist in the environment, such as
      hepatitis A virus (HAV), Norwalk-like virus (NLV), enterovirus (EV), rotavirus
      (RV), and astrovirus (AV), were detected by reverse transcription-PCR and
      hybridization in shellfish during a 3-year study. Oyster samples (n = 108),
      occasionally containing bacteria, were less frequently contaminated, showing
      positivity for AV (17%), NLV (23%), EV (19%), and RV (27%), whereas mussel
      samples, collected in areas routinely impacted by human sewage, were more highly
      contaminated: AV (50%), HAV (13%), NLV (35%), EV (45%), and RV (52%). Sequences
      obtained from HAV and NLV amplicons showed a great variety of strains, especially
      for NLV (strains close to Mexico, Snow Mountain Agent, or Norwalk virus). Viral
      contamination was mainly observed during winter months, although there were some
      seasonal differences among the viruses. This first study of virus detection over
      a fairly long period of time suggests that routine analysis of shellfish by a
      molecular technique is feasible.

PMID- 10919775
TI  - Comparative experiments to examine the effects of heating on vegetative cells and
      spores of Clostridium perfringens isolates carrying plasmid genes versus
      chromosomal enterotoxin genes.
AB  - Clostridium perfringens enterotoxin (CPE) is an important virulence factor for
      both C. perfringens type A food poisoning and several non-food-borne human
      gastrointestinal diseases. Recent studies have indicated that C. perfringens
      isolates associated with food poisoning carry a chromosomal cpe gene, while non
      food-borne human gastrointestinal disease isolates carry a plasmid cpe gene.
      However, no explanation has been provided for the strong associations between
      certain cpe genotypes and particular CPE-associated diseases. Since C.
      perfringens food poisoning usually involves cooked meat products, we hypothesized
      that chromosomal cpe isolates are so strongly associated with food poisoning
      because (i) they are more heat resistant than plasmid cpe isolates, (ii) heating
      induces loss of the cpe plasmid, or (iii) heating induces migration of the
      plasmid cpe gene to the chromosome. When we tested these hypotheses, vegetative
      cells of chromosomal cpe isolates were found to exhibit, on average approximately
      twofold-higher decimal reduction values (D values) at 55 degrees C than
      vegetative cells of plasmid cpe isolates exhibited. Furthermore, the spores of
      chromosomal cpe isolates had, on average, approximately 60-fold-higher D values
      at 100 degrees C than the spores of plasmid cpe isolates had. Southern
      hybridization and CPE Western blot analyses demonstrated that all survivors of
      heating retained their cpe gene in its original plasmid or chromosomal location
      and could still express CPE. These results suggest that chromosomal cpe isolates
      are strongly associated with food poisoning, at least in part, because their
      cells and spores possess a high degree of heat resistance, which should enhance
      their survival in incompletely cooked or inadequately warmed foods.

PMID- 10919777
TI  - Use of self-assembled monolayers of different wettabilities to study surface
      selection and primary adhesion processes of green algal (Enteromorpha) zoospores.
AB  - We investigated surface selection and adhesion of motile zoospores of a green,
      macrofouling alga (Enteromorpha) to self-assembled monolayers (SAMs) having a
      range of wettabilities. The SAMs were formed from alkyl thiols terminated with
      methyl (CH(3)) or hydroxyl (OH) groups or mixtures of CH(3)- and OH-terminated
      alkyl thiols and were characterized by measuring the advancing contact angles and
      by X-ray photoelectron spectroscopy. There was a positive correlation between the
      number of spores that attached to the SAMs and increasing contact angle
      (hydrophobicity). Moreover, the sizes of the spore groups (adjacent spores
      touching) were larger on the hydrophobic SAMs. Video microscopy of a patterned
      arrangement of SAMs showed that more zoospores were engaged in swimming and
      "searching" above the hydrophobic sectors than above the hydrophilic sectors,
      suggesting that the cells were able to "sense" that the hydrophobic surfaces were
      more favorable for settlement. The results are discussed in relation to the
      attachment of microorganisms to substrata having different wettabilities.

PMID- 10919779
TI  - Rhamnolipid-induced removal of lipopolysaccharide from Pseudomonas aeruginosa:
      effect on cell surface properties and interaction with hydrophobic substrates.
AB  - Little is known about the interaction of biosurfactants with bacterial cells.
      Recent work in the area of biodegradation suggests that there are two mechanisms
      by which biosurfactants enhance the biodegradation of slightly soluble organic
      compounds. First, biosurfactants can solubilize hydrophobic compounds within
      micelle structures, effectively increasing the apparent aqueous solubility of the
      organic compound and its availability for uptake by a cell. Second,
      biosurfactants can cause the cell surface to become more hydrophobic, thereby
      increasing the association of the cell with the slightly soluble substrate. Since
      the second mechanism requires very low levels of added biosurfactant, it is the
      more intriguing of the two mechanisms from the perspective of enhancing the
      biodegradation process. This is because, in practical terms, addition of low
      levels of biosurfactants will be more cost-effective for bioremediation. To
      successfully optimize the use of biosurfactants in the bioremediation process,
      their effect on cell surfaces must be understood. We report here that rhamnolipid
      biosurfactant causes the cell surface of Pseudomonas spp. to become hydrophobic
      through release of lipopolysaccharide (LPS). In this study, two Pseudomonas
      aeruginosa strains were grown on glucose and hexadecane to investigate the
      chemical and structural changes that occur in the presence of a rhamnolipid
      biosurfactant. Results showed that rhamnolipids caused an overall loss in
      cellular fatty acid content. Loss of fatty acids was due to release of LPS from
      the outer membrane, as demonstrated by 2-keto-3-deoxyoctonic acid and sodium
      dodecyl sulfate-polyacrylamide gel electrophoresis analysis and further confirmed
      by scanning electron microscopy. The amount of LPS loss was found to be dependent
      on rhamnolipid concentration, but significant loss occurred even at
      concentrations less than the critical micelle concentration. We conclude that
      rhamnolipid-induced LPS release is the probable mechanism of enhanced cell
      surface hydrophobicity.

PMID- 10919780
TI  - Distribution and diversity of archaea corresponding to the limnological cycle of
      a hypersaline stratified lake (Solar lake, Sinai, Egypt).
AB  - The vertical and seasonal distribution and diversity of archaeal sequences was
      investigated in a hypersaline, stratified, monomictic lake, Solar Lake, Sinai,
      Egypt, during the limnological development of stratification and mixing. Archaeal
      sequences were studied via phylogenetic analysis of 16S rDNA sequences as well as
      denaturing gradient gel electrophoresis analysis. The 165 clones studied were
      grouped into four phylogenetically different clusters. Most of the clones
      isolated from both the aerobic epilimnion and the sulfide-rich hypolimnion were
      defined as cluster I, belonging to the Halobacteriaceae family. The three
      additional clusters were all isolated from the anaerobic hypolimnion. Cluster II
      is phylogenetically located between the genera Methanobacterium and
      Methanococcus. Clusters III and IV relate to two previously documented groups of
      uncultured euryarchaeota, remotely related to the genus Thermoplasma. No
      crenarchaeota were found in the water column of the Solar Lake. The archaeal
      community in the Solar Lake under both stratified and mixed conditions was
      dominated by halobacteria in salinities higher than 10%. During stratification,
      additional clusters, some of which may possibly relate to uncultured halophilic
      methanogens, were found in the sulfide- and methane-rich hypolimnion.

PMID- 10919778
TI  - Chromosomal integration of tcb chlorocatechol degradation pathway genes as a
      means of expanding the growth substrate range of bacteria to include
      haloaromatics.
AB  - The tcbR-tcbCDEF gene cluster, coding for the chlorocatechol ortho-cleavage
      pathway in Pseudomonas sp. strain P51, has been cloned into a Tn5-based
      minitransposon. The minitransposon carrying the tcb gene cluster and a kanamycin
      resistance gene was transferred to Pseudomonas putida KT2442, and chromosomal
      integration was monitored by selection either for growth on 3-chlorobenzoate or
      for kanamycin resistance. Transconjugants able to utilize 3-chlorobenzoate as a
      sole carbon source were obtained, although at a >100-fold lower frequency than
      kanamycin-resistant transconjugants. The vast majority of kanamycin-resistant
      transconjugants were not capable of growth on 3-chlorobenzoate. Southern blot
      analysis revealed that many transconjugants selected directly on 3-chlorobenzoate
      contained multiple chromosomal copies of the tcb gene cluster, whereas those
      selected for kanamycin resistance possessed a single copy. Subsequent selection
      of kanamycin resistance-selected single-copy transconjugants for growth on 3
      chlorobenzoate yielded colonies capable of utilizing this carbon source, but no
      amplification of the tcb gene cluster was apparent. Introduction of two copies of
      the tcb gene cluster without prior 3-chlorobenzoate selection resulted in
      transconjugants able to grow on this carbon source. Expression of the tcb
      chlorocatechol catabolic operon in P. putida thus represents a useful model
      system for analysis of the relationship among gene dosage, enzyme expression
      level, and growth on chloroaromatic substrates.

PMID- 10919781
TI  - Production and characterization of two monoclonal antibodies specific for
      Plasmopara halstedii.
AB  - Sunflower downy mildew, caused by the fungus Plasmopara halstedii, is a
      potentially devastating disease. We produced two monoclonal antibodies (MAbs)
      (12C9 and 18E2) by immunizing mice with a partially purified extract of P.
      halstedii race 1. Both MAbs detected in enzyme-linked immunosorbent assay (ELISA)
      all races of P. halstedii present in France. No cross-reactions were observed
      with Plasmopara viticola or with other fungi commonly associated with sunflowers.
      Both MAbs recognized the same three fungal antigens with molecular masses of 68,
      140, and 192 kDa. However, the epitopes on the fungal antigens were distinct and
      repetitive. Seed homogenates from infected plants were incubated in wells coated
      with MAb 18E2. This resulted in the trapping of P. halstedii antigens that were
      identified with biotinylated MAb 12C9. No reactions were seen with seed
      homogenates from healthy plants. Thus, our results suggest that these MAbs might
      be used to develop a sandwich ELISA detection system for P. halstedii in infected
      seeds.

PMID- 10919782
TI  - Autocloning and amplification of LIP2 in Yarrowia lipolytica.
AB  - We synthesized a Yarrowia lipolytica strain overproducing lipase for industrial
      applications by using long terminal repeat (zeta) of the Y. lipolytica
      retrotransposon Ylt1 and an allele of URA3 with a promoter deletion to construct
      JMP3. JMP3 is a derivative of plasmid pHSS6 carrying a NotI-NotI cassette which
      contains a defective URA3 allele, a polylinker sequence, and the zeta region for
      targeting to multiple sites in the genome of the recipient. We inserted the LIP2
      gene (encoding extracellular lipase) under the control of the strong POX2
      promoter into JMP3 to generate JMP6. The pHSS6 region was removed by NotI
      digestion prior to transformation. Two Y. lipolytica strains transformed with the
      JMP6 LIP2 cassette had a mean of 10 integrated copies devoid of the Escherichia
      coli region, corresponding to an autocloning event. The copy number in the
      transformants was stable even after 120 generations in nonselective and lipase
      inducing conditions. The resulting strains could produce 0.5 g of active lipase
      per liter in the supernatant, 40 times more than the single-copy strain with the
      LIP2 promoter. This work provides a new expression system in Y. lipolytica that
      results in strains devoid of bacterial DNA and in strains producing a high level
      of lipase for industrial uses, waste treatment, and pancreatic insufficiency
      therapy.

PMID- 10919783
TI  - Changes in bacterial community structure in the colon of pigs fed different
      experimental diets and after infection with Brachyspira hyodysenteriae.
AB  - Bacterial communities in the large intestines of pigs were compared using
      terminal restriction fragment length polymorphism (T-RFLP) analysis targeting the
      16S ribosomal DNA. The pigs were fed different experimental diets based on either
      modified standard feed or cooked rice supplemented with dietary fibers. After
      feeding of the animals with the experimental diets for 2 weeks, differences in
      the bacterial community structure in the spiral colon were detected in the form
      of different profiles of terminal restriction fragments (T-RFs). Some of the T
      RFs were universally distributed, i.e., they were found in all samples, while
      others varied in distribution and were related to specific diets. The
      reproducibility of the T-RFLP profiles between individual animals within the diet
      groups was high. In the control group, the profiles remained unchanged throughout
      the experiment and were similar between two independent but identical
      experiments. When the animals were experimentally infected with Brachyspira
      hyodysenteriae, causing swine dysentery, many of the T-RFs fluctuated, suggesting
      a destabilization of the microbial community.

PMID- 10919784
TI  - Effect of dissemination of 2,4-dichlorophenoxyacetic acid (2,4-D) degradation
      plasmids on 2,4-D degradation and on bacterial community structure in two
      different soil horizons.
AB  - Transfer of the 2,4-dichlorophenoxyacetic acid (2,4-D) degradation plasmids pEMT1
      and pJP4 from an introduced donor strain, Pseudomonas putida UWC3, to the
      indigenous bacteria of two different horizons (A horizon, depth of 0 to 30 cm; B
      horizon, depth of 30 to 60 cm) of a 2,4-D-contaminated soil was investigated as a
      means of bioaugmentation. When the soil was amended with nutrients, plasmid
      transfer and enhanced degradation of 2,4-D were observed. These findings were
      most striking in the B horizon, where the indigenous bacteria were unable to
      degrade any of the 2,4-D (100 mg/kg of soil) during at least 22 days but where
      inoculation with either of the two plasmid donors resulted in complete 2,4-D
      degradation within 14 days. In contrast, in soils not amended with nutrients,
      inoculation of donors in the A horizon and subsequent formation of
      transconjugants (10(5) CFU/g of soil) could not increase the 2,4-D degradation
      rate compared to that of the noninoculated soil. However, donor inoculation in
      the nonamended B-horizon soil resulted in complete degradation of 2,4-D within 19
      days, while no degradation at all was observed in noninoculated soil during 89
      days. With plasmid pEMT1, this enhanced degradation seemed to be due only to
      transconjugants (10(5) CFU/g of soil), since the donor was already undetectable
      when degradation started. Denaturing gradient gel electrophoresis (DGGE) of 16S
      rRNA genes showed that inoculation of the donors was followed by a shift in the
      microbial community structure of the nonamended B-horizon soils. The new 16S rRNA
      gene fragments in the DGGE profile corresponded with the 16S rRNA genes of 2,4-D
      degrading transconjugant colonies isolated on agar plates. This result indicates
      that the observed change in the community was due to proliferation of
      transconjugants formed in soil. Overall, this work clearly demonstrates that
      bioaugmentation can constitute an effective strategy for cleanup of soils which
      are poor in nutrients and microbial activity, such as those of the B horizon.

PMID- 10919785
TI  - Polyamine composition and expression of genes related to polyamine biosynthesis
      in an aphid endosymbiont, Buchnera.
AB  - Polyamine composition in an aphid endosymbiotic bacterium, Buchnera sp., was
      determined by high-performance liquid chromatographic analysis. We found that
      Buchnera contained virtually only a single polyamine, spermidine. The spermidine
      content of Buchnera was considerably higher in young aphids and tended to
      decrease with the age of the host. Expression of speD and speE, whose gene
      products are key enzymes in the synthesis of spermidine, was analyzed by real
      time quantitative reverse transcription-PCR. It was shown that the levels of
      their mRNAs fluctuated in line with the spermidine content.

PMID- 10919787
TI  - Genotypic heterogeneity of Streptococcus oralis and distinct aciduric
      subpopulations in human dental plaque.
AB  - The genotypic heterogeneity of Streptococcus oralis isolated from the oral cavity
      was investigated using repetitive extragenic palindromic PCR. Unrelated subjects
      harbored unique genotypes, with numerous genotypes being isolated from an
      individual. S. oralis is the predominant aciduric bacterium isolated from
      noncarious tooth sites. Genotypic comparison of the aciduric populations isolated
      at pH 5.2 with those isolated from mitis-salivarius agar (MSA) (pH 7.0) indicated
      that the aciduric populations were genotypically distinct in the majority of
      subjects (chi(2) = 13.09; P = 0.0031). Neither the aciduric nor the MSA-isolated
      strains were stable, with no strains isolated at baseline being isolated 4 or 12
      weeks later in the majority of subjects. The basis of this instability is unknown
      but is similar to that reported for Streptococcus mitis. Examination of S. oralis
      strains isolated from cohabiting couples demonstrated that in three of five
      couples, genotypically identical strains were isolated from both partners and
      this was confirmed by using Salmonella enteritidis repetitive element PCR and
      enterobacterial PCR typing. These data provide further evidence of the
      physiological and genotypic heterogeneity of non-mutans streptococci. The
      demonstration of distinct aciduric populations of S. oralis implies that the role
      of these and other non-mutans streptococci in the caries process requires
      reevaluation.

PMID- 10919788
TI  - A novel protein-deamidating enzyme from Chryseobacterium proteolyticum sp. nov.,
      a newly isolated bacterium from soil.
AB  - A novel protein-deamidating enzyme, which has potential for industrial
      applications, was purified from the culture supernatant of Chryseobacterium
      proteolyticum strain 9670(T) isolated from rice field soil in Tsukuba, Japan. The
      deamidating activities on carboxybenzoxy (Cbz)-Gln-Gly and caseins and protease
      activity were produced synchronously by the isolate. Both deamidating activities
      were eluted as identical peaks separated from several proteases by phenyl
      Sepharose chromatography of the culture supernatant. The enzyme catalyzed the
      deamidation of native caseins with no protease and transglutaminase activities.
      Phenotypic characterization and DNA analyses of the isolate were performed to
      determine its taxonomy. Physiological and biochemical characteristics, 16S rRNA
      gene sequence analysis, and DNA-DNA relatedness data indicated that the isolate
      should be placed as a new species belonging to the genus Chryseobacterium. The
      isolate showed no growth on MacConkey agar and produced acid from sucrose. The
      levels of DNA-DNA relatedness between the isolate and other related strains were
      less than 17%. The name Chryseobacterium proteolyticum is proposed for the new
      species; strain 9670 is the type strain (=FERM P-17664).

PMID- 10919790
TI  - Comparative characterization of complete and truncated forms of Lactobacillus
      amylovorus alpha-amylase and role of the C-terminal direct repeats in raw-starch
      binding.
AB  - Two constructs derived from the alpha-amylase gene (amyA) of Lactobacillus
      amylovorus were expressed in Lactobacillus plantarum, and their expression
      products were purified, characterized, and compared. These products correspond to
      the complete (AmyA) and truncated (AmyADelta) forms of alpha-amylase; AmyADelta
      lacks the 66-kDa carboxyl-terminal direct-repeating-unit region. AmyA and
      AmyADelta exhibit similar amylase activities towards a range of soluble
      substrates (amylose, amylopectin and alpha-cyclodextrin, and soluble starch). The
      specific activities of the enzymes towards soluble starch are similar, but the
      K(M) and V(max) values of AmyADelta were slightly higher than those of AmyA,
      whereas the thermal stability of AmyADelta was lower than that of AmyA. In
      contrast to AmyA, AmyADelta is unable to bind to beta-cyclodextrin and is only
      weakly active towards glycogen. More striking is the fact that AmyADelta cannot
      bind or hydrolyze raw starch, demonstrating that the carboxyl-terminal repeating
      unit domain of AmyA is required for raw-starch binding activity.

PMID- 10919789
TI  - Extensive polymorphism in Cryptosporidium parvum identified by multilocus
      microsatellite analysis.
AB  - Restriction fragment length polymorphism and DNA sequence analysis discern two
      main types of Cryptosporidium parvum. We present a survey of length polymorphism
      at several microsatellite loci for type 1 and type 2 isolates. A total of 14
      microsatellite loci were identified from C. parvum DNA sequences deposited in
      public databases. All repeats were mono-, di-, and trinucleotide repeats of A,
      AT, and AAT, reflecting the high AT content of the C. parvum genome. Several of
      these loci showed significant length polymorphism, with as many as seven alleles
      identified for a single locus. Differences between alleles ranged from 1 to 27
      bp. Karyotype analysis using probes flanking three microsatellites localized each
      marker to an individual chromosomal band, suggesting that these markers are
      single copy. In a sample of 19 isolates for which at least three microsatellites
      were typed, a majority of isolates displayed a unique multilocus fingerprint.
      Microsatellite analysis of isolates passaged between different host species
      identified genotypic changes consistent with changes in parasite populations.

PMID- 10919786
TI  - A genomic sample sequence of the entomopathogenic bacterium Photorhabdus
      luminescens W14: potential implications for virulence.
AB  - Photorhabdus luminescens is a pathogenic bacterium that lives in the guts of
      insect-pathogenic nematodes. After invasion of an insect host by a nematode,
      bacteria are released from the nematode gut and help kill the insect, in which
      both the bacteria and the nematodes subsequently replicate. However, the
      bacterial virulence factors associated with this "symbiosis of pathogens" remain
      largely obscure. In order to identify genes encoding potential virulence factors,
      we performed approximately 2,000 random sequencing reads from a P. luminescens
      W14 genomic library. We then compared the sequences obtained to sequences in
      existing gene databases and to the Escherichia coli K-12 genome sequence. Here we
      describe the different classes of potential virulence factors found. These
      factors include genes that putatively encode Tc insecticidal toxin complexes, Rtx
      like toxins, proteases and lipases, colicin and pyocins, and various antibiotics.
      They also include a diverse array of secretion (e.g., type III), iron uptake, and
      lipopolysaccharide production systems. We speculate on the potential functions of
      each of these gene classes in insect infection and also examine the extent to
      which the invertebrate pathogen P. luminescens shares potential antivertebrate
      virulence factors. The implications for understanding both the biology of this
      insect pathogen and links between the evolution of vertebrate virulence factors
      and the evolution of invertebrate virulence factors are discussed.

PMID- 10919791
TI  - Decolorization and detoxification of textile dyes with a laccase from Trametes
      hirsuta.
AB  - Trametes hirsuta and a purified laccase from this organism were able to degrade
      triarylmethane, indigoid, azo, and anthraquinonic dyes. Initial decolorization
      velocities depended on the substituents on the phenolic rings of the dyes.
      Immobilization of the T. hirsuta laccase on alumina enhanced the thermal
      stabilities of the enzyme and its tolerance against some enzyme inhibitors, such
      as halides, copper chelators, and dyeing additives. The laccase lost 50% of its
      activity at 50 mM NaCl while the 50% inhibitory concentration (IC(50)) of the
      immobilized enzyme was 85 mM. Treatment of dyes with the immobilized laccase
      reduced their toxicities (based on the oxygen consumption rate of Pseudomonas
      putida) by up to 80% (anthraquinonic dyes). Textile effluents decolorized with T.
      hirsuta or the laccase were used for dyeing. Metabolites and/or enzyme protein
      strongly interacted with the dyeing process indicated by lower staining levels
      (K/S) values than obtained with a blank using water. However, when the effluents
      were decolorized with immobilized laccase, they could be used for dyeing and
      acceptable color differences (DeltaE*) below 1.1 were measured for most dyes.

PMID- 10919792
TI  - Microbial biofilm formation and contamination of dental-unit water systems in
      general dental practice.
AB  - Dental-unit water systems (DUWS) harbor bacterial biofilms, which may serve as a
      haven for pathogens. The aim of this study was to investigate the microbial load
      of water from DUWS in general dental practices and the biofouling of DUWS tubing.
      Water and tube samples were taken from 55 dental surgeries in southwestern
      England. Contamination was determined by viable counts on environmentally
      selective, clinically selective, and pathogen-selective media, and biofouling was
      determined by using microscopic and image analysis techniques. Microbial loading
      ranged from 500 to 10(5) CFU. ml(-1); in 95% of DUWS water samples, it exceeded
      European Union drinking water guidelines and in 83% it exceeded American Dental
      Association DUWS standards. Among visible bacteria, 68% were viable by BacLight
      staining, but only 5% of this "viable by BacLight" fraction produced colonies on
      agar plates. Legionella pneumophila, Mycobacterium spp., Candida spp., and
      Pseudomonas spp. were detected in one, five, two, and nine different surgeries,
      respectively. Presumptive oral streptococci and Fusobacterium spp. were detected
      in four and one surgeries, respectively, suggesting back siphonage and failure of
      antiretraction devices. Hepatitis B virus was never detected. Decontamination
      strategies (5 of 55 surgeries) significantly reduced biofilm coverage but
      significantly increased microbial numbers in the water phase (in both cases, P <
      0.05). Microbial loads were not significantly different in DUWS fed with soft,
      hard, deionized, or distilled water or in different DUWS (main, tank, or bottle
      fed). Microbiologically, no DUWS can be considered "cleaner" than others. DUWS
      deliver water to patients with microbial levels exceeding those considered safe
      for drinking water.

PMID- 10919793
TI  - Knockout of the p-coumarate decarboxylase gene from Lactobacillus plantarum
      reveals the existence of two other inducible enzymatic activities involved in
      phenolic acid metabolism.
AB  - Lactobacillus plantarum NC8 contains a pdc gene coding for p-coumaric acid
      decarboxylase activity (PDC). A food grade mutant, designated LPD1, in which the
      chromosomal pdc gene was replaced with the deleted pdc gene copy, was obtained by
      a two-step homologous recombination process using an unstable replicative vector.
      The LPD1 mutant strain remained able to weakly metabolize p-coumaric and ferulic
      acids into vinyl derivatives or into substituted phenyl propionic acids. We have
      shown that L. plantarum has a second acid phenol decarboxylase enzyme, better
      induced with ferulic acid than with p-coumaric acid, which also displays
      inducible acid phenol reductase activity that is mostly active when glucose is
      added. Those two enzymatic activities are in competition for p-coumaric and
      ferulic acid degradation, and the ratio of the corresponding derivatives depends
      on induction conditions. Moreover, PDC appeared to decarboxylate ferulic acid in
      vitro with a specific activity of about 10 nmol. min(-1). mg(-1) in the presence
      of ammonium sulfate. Finally, PDC activity was shown to confer a selective
      advantage on LPNC8 grown in acidic media supplemented with p-coumaric acid,
      compared to the LPD1 mutant devoid of PDC activity.

PMID- 10919794
TI  - rpoB-based microbial community analysis avoids limitations inherent in 16S rRNA
      gene intraspecies heterogeneity.
AB  - Contemporary microbial community analysis frequently involves PCR-amplified
      sequences of the 16S rRNA gene (rDNA). However, this technology carries the
      inherent problem of heterogeneity between copies of the 16S rDNA in many species.
      As an alternative to 16S rDNA sequences in community analysis, we employed the
      gene for the RNA polymerase beta subunit (rpoB), which appears to exist in one
      copy only in bacteria. In the present study, the frequency of 16S rDNA
      heterogeneity in bacteria isolated from the marine environment was assessed using
      bacterial isolates from the red alga Delisea pulchra and from the surface of a
      marine rock. Ten strains commonly used in our laboratory were also assessed for
      the degree of heterogeneity between the copies of 16S rDNA and were used to
      illustrate the effect of this heterogeneity on microbial community pattern
      analysis. The rock isolates and the laboratory strains were also used to confirm
      nonheterogeneity of rpoB, as well as to investigate the versatility of the
      primers. In addition, a comparison between 16S rDNA and rpoB PCR-DGGE (denaturing
      gradient gel electrophoresis)-based community analyses was performed using a DNA
      mixture of nine isolates from D. pulchra. Eight out of 14 isolates from D.
      pulchra, all rock isolates, and 6 of 10 laboratory strains displayed multiple
      bands for 16S rDNA when analyzed by DGGE. There was no indication of
      heterogeneity for either the rock isolates or the laboratory strains when rpoB
      was used for PCR-DGGE analysis. Microbial community pattern analysis using 16S
      rDNA PCR-DGGE showed an overestimation of the number of laboratory strains in the
      sample, while some strains were not represented. Therefore, the 16S rDNA PCR-DGGE
      based community analysis was proven to be severely limited by 16S rDNA
      heterogeneity. The mixture of isolates from D. pulchra proved to be more
      accurately described using rpoB, compared to the 16S rDNA-based PCR-DGGE.

PMID- 10919795
TI  - Anaerobic xylose fermentation by recombinant Saccharomyces cerevisiae carrying
      XYL1, XYL2, and XKS1 in mineral medium chemostat cultures.
AB  - For ethanol production from lignocellulose, the fermentation of xylose is an
      economic necessity. Saccharomyces cerevisiae has been metabolically engineered
      with a xylose-utilizing pathway. However, the high ethanol yield and productivity
      seen with glucose have not yet been achieved. To quantitatively analyze metabolic
      fluxes in recombinant S. cerevisiae during metabolism of xylose-glucose mixtures,
      we constructed a stable xylose-utilizing recombinant strain, TMB 3001. The XYL1
      and XYL2 genes from Pichia stipitis, encoding xylose reductase (XR) and xylitol
      dehydrogenase (XDH), respectively, and the endogenous XKS1 gene, encoding
      xylulokinase (XK), under control of the PGK1 promoter were integrated into the
      chromosomal HIS3 locus of S. cerevisiae CEN.PK 113-7A. The strain expressed XR,
      XDH, and XK activities of 0.4 to 0.5, 2.7 to 3.4, and 1.5 to 1.7 U/mg,
      respectively, and was stable for more than 40 generations in continuous
      fermentations. Anaerobic ethanol formation from xylose by recombinant S.
      cerevisiae was demonstrated for the first time. However, the strain grew on
      xylose only in the presence of oxygen. Ethanol yields of 0.45 to 0.50 mmol of
      C/mmol of C (0.35 to 0.38 g/g) and productivities of 9.7 to 13.2 mmol of C h(-1)
      g (dry weight) of cells(-1) (0.24 to 0.30 g h(-1) g [dry weight] of cells(-1))
      were obtained from xylose-glucose mixtures in anaerobic chemostat cultures, with
      a dilution rate of 0.06 h(-1). The anaerobic ethanol yield on xylose was
      estimated at 0.27 mol of C/(mol of C of xylose) (0.21 g/g), assuming a constant
      ethanol yield on glucose. The xylose uptake rate increased with increasing xylose
      concentration in the feed, from 3.3 mmol of C h(-1) g (dry weight) of cells(-1)
      when the xylose-to-glucose ratio in the feed was 1:3 to 6.8 mmol of C h(-1) g
      (dry weight) of cells(-1) when the feed ratio was 3:1. With a feed content of 15
      g of xylose/liter and 5 g of glucose/liter, the xylose flux was 2.2 times lower
      than the glucose flux, indicating that transport limits the xylose flux.

PMID- 10919796
TI  - Light and the transcriptional response of the microcystin biosynthesis gene
      cluster.
AB  - Microcystin, a hepatotoxin known to be the cause of animal and human deaths, is
      produced by the bloom-forming cyanobacterium Microcystis aeruginosa in freshwater
      bodies worldwide. The toxin is produced nonribosomally via a multifunctional
      enzyme complex, consisting of both peptide synthetase and polyketide synthase
      modules coded for by the mcy gene cluster. The recent identification of the mcy
      genes in the production of microcystin synthetase for the first time provides an
      avenue to study the regulation of microcystin production at a genetic level. In
      this study, M. aeruginosa PCC7806 was grown either under continuous light of
      various intensities or under low light with subsequent short-term exposure to
      different light intensities and qualities and various stress factors. RNase
      protection assays were employed to observe the level of mcyB and mcyD
      transcription under each condition. Both mcyB and mcyD transcript levels were
      increased under high light intensities and red light. Blue light and certain
      artificial stress factors (methylviologen and NaCl) led to reduced transcript
      amounts. There appeared to be two light thresholds, between dark and low light
      (16 micromol of photons m(-2) s(-1)), and medium (31 micromol of photons m(-2) s(
      1)) and high light (68 micromol of photons m(-2) s(-1)), at which a significant
      increase in transcription occurred. Our findings show that the effect of light on
      microcystin synthetase production is due to light quality and is initiated at
      certain threshold intensities, which are not necessarily reflected by observed
      intracellular toxin bioactivity.

PMID- 10919797
TI  - Rhizosphere soil aggregation and plant growth promotion of sunflowers by an
      exopolysaccharide-producing Rhizobium sp. strain isolated from sunflower roots.
AB  - Root-adhering soil (RAS) forms the immediate environment where plants take up
      water and nutrients for their growth. We report the effect of an
      exopolysaccharide (EPS)-producing rhizobacterium (strain YAS34) on the physical
      properties of sunflower (Helianthus annuus L.) RAS, associated with plant growth
      promotion, under both water stress and normal water supply conditions. Strain
      YAS34 was isolated as a major EPS-producing bacterium from the rhizoplane of
      sunflowers grown in a French dystric cambisol. Strain YAS34 was assigned to the
      Rhizobium genus by 16S ribosomal DNA gene sequencing. Inoculation of sunflower
      seeds and soil with strain YAS34 caused a significant increase in RAS per root
      dry mass (dm) (up to 100%) and a significant increase in soil macropore volume
      (12 to 60 microm in diameter). The effect of inoculation on sunflower shoot dm
      (up to +50%) and root dm (up to +70%) was significant under both normal and water
      stress conditions. Inoculation with strain YAS34 modified soil structure around
      the root system, counteracting the negative effect of water deficit on growth.
      Using [(15)N]nitrate, we showed that inoculation made the use of fertilizer more
      effective by increasing nitrogen uptake by sunflower plantlets.

PMID- 10919799
TI  - Accumulation of Poly[(R)-3-hydroxyalkanoates] in Pseudomonas oleovorans during
      growth with octanoate in continuous culture at different dilution rates.
AB  - Pseudomonas oleovorans ATCC 29347 was grown in chemostat culture at different
      dilution rates with mineral media varying in their ratios of octanoate to ammonia
      (C(0)/N(0) ratio). At all dilution rates tested, three distinct growth regimes
      were observed: (i) carbon limitation with NH(4)(+) in excess at low C(0)/N(0)
      ratios, (ii) purely nitrogen-limited growth conditions at high C(0)/N(0) ratios
      with residual octanoate in the culture supernatant, and (iii) an intermediate
      zone of dual-nutrient-limited growth conditions where both the concentration of
      octanoate and that of ammonia were very low. The dual-nutrient-limited growth
      zone shifted to higher C(0)/N(0) ratios with decreasing dilution rates, and the
      extension of the dual-nutrient-limited growth zone was inversely proportional to
      the growth rate. The cells accumulated the storage compound medium-chain-length
      poly[(R)-3-hydroxyalkanoate] (mcl-PHA) during dual (C and N)-nutrient-limited and
      N-limited growth conditions. Within the dual-nutrient-limited growth zone, the
      cellular mcl-PHA contents increased when the C(0)/N(0) ratio in the feed was
      increased, whereas the cellular mcl-PHA level was independent from the feed
      C(0)/N(0) ratio during N-limited growth. The monomeric composition of the
      accumulated mcl-PHA was independent of both the dilution rate and the feed
      C(0)/N(0) ratio and consisted of 12 mol% 3-hydroxyhexanoic acid and 88 mol% 3
      hydroxyoctanoic acid. Accumulation of mcl-PHA led to an increase in the cellular
      C/N ratio and to changes in elemental growth yields for nitrogen and carbon.

PMID- 10919798
TI  - Comparison of 2,4-dichlorophenoxyacetic acid degradation and plasmid transfer in
      soil resulting from bioaugmentation with two different pJP4 donors.
AB  - A pilot field study was conducted to assess the impact of bioaugmentation with
      two plasmid pJP4-bearing microorganisms: the natural host, Ralstonia eutropha
      JMP134, and a laboratory-generated strain amenable to donor counterselection,
      Escherichia coli D11. The R. eutropha strain contained chromosomal genes
      necessary for mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D), while the
      E. coli strain did not. The soil system was contaminated with 2,4-D alone or was
      cocontaminated with 2,4-D and Cd. Plasmid transfer to indigenous populations,
      plasmid persistence in soil, and degradation of 2,4-D were monitored over a 63
      day period in the bioreactors. To assess the impact of contaminant reexposure,
      aliquots of bioreactor soil were reamended with additional 2,4-D. Both introduced
      donors remained culturable and transferred plasmid pJP4 to indigenous recipients,
      although to different extents. Isolated transconjugants were members of the
      Burkholderia and Ralstonia genera, suggesting multiple, if not successive,
      plasmid transfers. Upon a second exposure to 2,4-D, enhanced degradation was
      observed for all treatments, suggesting microbial adaptation to 2,4-D. Upon
      reexposure, degradation was most rapid for the E. coli D11-inoculated treatments.
      Cd did not significantly impact 2,4-D degradation or transconjugant formation.
      This study demonstrated that the choice of donor microorganism might be a key
      factor to consider for bioaugmentation efforts. In addition, the establishment of
      an array of stable indigenous plasmid hosts at sites with potential for
      reexposure or long-term contamination may be particularly useful.

PMID- 10919800
TI  - Quantitative determination of the biodegradable polymer Poly(beta
      hydroxybutyrate) in a recombinant Escherichia coli strain by use of mid-infrared
      spectroscopy and multivariative statistics.
AB  - Fourier transform infrared (FTIR) spectroscopy in combination with the partial
      least squares (PLS) multivariative statistical technique was used for
      quantitative analysis of the poly(beta-hydroxybutyrate) (PHB) contents of
      bacterial cells. A total of 237 replicate spectra from 34 samples were obtained
      together with gas chromatography-determined reference PHB contents. Using the PLS
      regression, we were able to relate the infrared spectra to the reference PHB
      contents, and the correlation coefficient between the measured and predicted
      values for the optimal model with a standard error of prediction of 1.49% PHB was
      0.988. With this technique, there are no solvent requirements, sample preparation
      is minimal and simple, and analysis time is greatly reduced; our results
      demonstrate the potential of FTIR spectroscopy as an alternative to the
      conventional methods used for analysis of PHB in bacterial cells.

PMID- 10919801
TI  - Tandem repeat of a transcriptional enhancer upstream of the sterol 14alpha
      demethylase gene (CYP51) in Penicillium digitatum.
AB  - We investigated the mechanism of resistance to demethylation inhibitors (DMI) in
      Penicillium digitatum by isolating the CYP51 gene, which encodes the target
      enzyme (P450(14DM)) of DMI, from three DMI-resistant and three DMI-sensitive
      strains. The structural genes of all six strains were identical, but in the
      promoter region, a unique 126-bp sequence was tandemly repeated five times in the
      DMI-resistant strains and was present only once in the DMI-sensitive strains.
      Constitutive expression of CYP51 in the resistant strains was about 100-fold
      higher than that in the sensitive strains. We introduced CYP51, including the
      promoter region, from a DMI-resistant strain into a DMI-sensitive strain, which
      rendered the transformants DMI resistant and increased CYP51 expression. We also
      found that if the number of copies of the repeat was reduced to two, resistance
      and CYP51 expression also decreased. These results indicate that the 126-bp unit
      acts as a transcriptional enhancer and that a tandem repeat of the unit enhances
      CYP51 expression, resulting in DMI resistance. This is a new fungicide resistance
      mechanism for filamentous fungi.

PMID- 10919802
TI  - Factors affecting exocellular polysaccharide production by Lactobacillus
      delbrueckii subsp. bulgaricus grown in a chemically defined medium.
AB  - We developed a chemically defined medium (CDM) containing lactose or glucose as
      the carbon source that supports growth and exopolysaccharide (EPS) production of
      two strains of Lactobacillus delbrueckii subsp. bulgaricus. The factors found to
      affect EPS production in this medium were oxygen, pH, temperature, and medium
      constituents, such as orotic acid and the carbon source. EPS production was
      greatest during the stationary phase. Composition analysis of EPS isolated at
      different growth phases and produced under different fermentation conditions
      (varying carbon source or pH) revealed that the component sugars were the same.
      The EPS from strain L. delbrueckii subsp. bulgaricus CNRZ 1187 contained
      galactose and glucose, and that of strain L. delbrueckii subsp. bulgaricus CNRZ
      416 contained galactose, glucose, and rhamnose. However, the relative proportions
      of the individual monosaccharides differed, suggesting that repeating unit
      structures can vary according to specific medium alterations. Under pH-controlled
      fermentation conditions, L. delbrueckii subsp. bulgaricus strains produced as
      much EPS in the CDM as in milk. Furthermore, the relative proportions of
      individual monosaccharides of EPS produced in pH-controlled CDM or in milk were
      very similar. The CDM we developed may be a useful model and an alternative to
      milk in studies of EPS production.

PMID- 10919803
TI  - Rapid methods for testing the efficacy of sterilization-grade filter membranes.
AB  - The validation of sterilization-grade membranes is integral to ensuring the
      efficient and safe use of microfiltration systems. Here validation refers to the
      production of sterile filtrate for sterilizing-grade membranes under challenge
      test conditions. Current validation methods require 48 h of culture for results
      to become available, which creates time delays within the manufacturing process
      and quality control (QC) backlogs. This work compares four methods for the
      production of filter challenge test data, to the desired test sensitivity, within
      24 h using bioluminescent and fluorescent recombinant strains of the test
      organism Brevundimonas diminuta. These methods should provide a way to implement
      more rapid QC test regimens for filters.

PMID- 10919804
TI  - Affinity purification of DNA and RNA from environmental samples with peptide
      nucleic acid clamps.
AB  - Bispeptide nucleic acids (bis-PNAs; PNA clamps), PNA oligomers, and DNA
      oligonucleotides were evaluated as affinity purification reagents for
      subfemtomolar 16S ribosomal DNA (rDNA) and rRNA targets in soil, sediment, and
      industrial air filter nucleic acid extracts. Under low-salt hybridization
      conditions (10 mM NaPO(4), 5 mM disodium EDTA, and 0.025% sodium dodecyl sulfate
      [SDS]) a PNA clamp recovered significantly more target DNA than either PNA or DNA
      oligomers. The efficacy of PNA clamps and oligomers was generally enhanced in the
      presence of excess nontarget DNA and in a low-salt extraction-hybridization
      buffer. Under high-salt conditions (200 mM NaPO(4), 100 mM disodium EDTA, and
      0.5% SDS), however, capture efficiencies with the DNA oligomer were significantly
      greater than with the PNA clamp and PNA oligomer. Recovery and detection
      efficiencies for target DNA concentrations of > or =100 pg were generally >20%
      but depended upon the specific probe, solution background, and salt condition.
      The DNA probe had a lower absolute detection limit of 100 fg of target (830 zM [1
      zM = 10(-21) M]) in high-salt buffer. In the absence of exogenous DNA (e.g., soil
      background), neither the bis-PNA nor the PNA oligomer achieved the same absolute
      detection limit even under a more favorable low-salt hybridization condition. In
      the presence of a soil background, however, both PNA probes provided more
      sensitive absolute purification and detection (830 zM) than the DNA oligomer. In
      varied environmental samples, the rank order for capture probe performance in
      high-salt buffer was DNA > PNA > clamp. Recovery of 16S rRNA from environmental
      samples mirrored quantitative results for DNA target recovery, with the DNA
      oligomer generating more positive results than either the bis-PNA or PNA
      oligomer, but PNA probes provided a greater incidence of detection from
      environmental samples that also contained a higher concentration of nontarget DNA
      and RNA. Significant interactions between probe type and environmental sample
      indicate that the most efficacious capture system depends upon the particular
      sample type (and background nucleic acid concentration), target (DNA or RNA), and
      detection objective.

PMID- 10919805
TI  - Isolation and characterization of diverse halobenzoate-degrading denitrifying
      bacteria from soils and sediments.
AB  - Denitrifying bacteria capable of degrading halobenzoates were isolated from
      various geographical and ecological sites. The strains were isolated after
      initial enrichment on one of the monofluoro-, monochloro-, or monobromo-benzoate
      isomers with nitrate as an electron acceptor, yielding a total of 33 strains
      isolated from the different halobenzoate-utilizing enrichment cultures. Each
      isolate could grow on the selected halobenzoate with nitrate as the terminal
      electron acceptor. The isolates obtained on 2-fluorobenzoate could use 2
      fluorobenzoate under both aerobic and denitrifying conditions, but did not
      degrade other halobenzoates. In contrast, the 4-fluorobenzoate isolates degraded
      4-fluorobenzoate under denitrifying conditions only, but utilized 2
      fluorobenzoate under both aerobic and denitrifying conditions. The strains
      isolated on either 3-chlorobenzoate or 3-bromobenzoate could use 3
      chlorobenzoate, 3-bromobenzoate, and 2- and 4-fluorobenzoates under denitrifying
      conditions. The isolates were identified and classified on the basis of 16S rRNA
      gene sequence analysis and their cellular fatty acid profiles. They were placed
      in nine genera belonging to either the alpha-, beta-, or gamma-branch of the
      Proteobacteria, namely, Acidovorax, Azoarcus, Bradyrhizobium, Ochrobactrum,
      Paracoccus, Pseudomonas, Mesorhizobium, Ensifer, and Thauera. These results
      indicate that the ability to utilize different halobenzoates under denitrifying
      conditions is ubiquitously distributed in the Proteobacteria and that these
      bacteria are widely distributed in soils and sediments.

PMID- 10919806
TI  - Genetic diversity among Arthrobacter species collected across a heterogeneous
      series of terrestrial deep-subsurface sediments as determined on the basis of 16S
      rRNA and recA gene sequences.
AB  - This study was undertaken in an effort to understand how the population structure
      of bacteria within terrestrial deep-subsurface environments correlates with the
      physical and chemical structure of their environment. Phylogenetic analysis was
      performed on strains of Arthrobacter that were collected from various depths,
      which included a number of different sedimentary units from the Yakima Barricade
      borehole at the U.S. Department of Energy's Hanford site, Washington, in August
      1992. At the same time that bacteria were isolated, detailed information on the
      physical, chemical, and microbiological characteristics of the sediments was
      collected. Phylogenetic trees were prepared from the 39 deep-subsurface
      Arthrobacter isolates (as well as 17 related type strains) based on 16S rRNA and
      recA gene sequences. Analyses based on each gene independently were in general
      agreement. These analyses showed that, for all but one of the strata (sedimentary
      layers characterized by their own unifying lithologic composition), the deep
      subsurface isolates from the same stratum are largely monophyletic. Notably, the
      layers for which this is true were composed of impermeable sediments. This
      suggests that the populations within each of these strata have remained isolated
      under constant, uniform conditions, which have selected for a particular dominant
      genotype in each stratum. Conversely, the few strains isolated from a gravel-rich
      layer appeared along several lineages. This suggests that the higher-permeability
      gravel decreases the degree of isolation of this population (through greater
      groundwater flow), creating fluctuations in environmental conditions or allowing
      migration, such that a dominant population has not been established. No
      correlation was seen between the relationship of the strains and any particular
      chemical or physical characteristics of the sediments. Thus, this work suggests
      that within sedimentary deep-subsurface environments, permeability of the
      deposits plays a major role in determining the genetic structure of resident
      bacterial populations.

PMID- 10919807
TI  - Immunomagnetic purification of Colletotrichum lindemuthianum appressoria.
AB  - We developed a method to purify appressoria of the bean anthracnose fungus
      Colletotrichum lindemuthianum for biochemical analysis of the cell surface and to
      compare appressoria with other fungal structures. We used immunomagnetic
      separation after incubation of infected bean leaf homogenates with a monoclonal
      antibody that binds strongly to the appressoria. Preparations with a purity of
      >90% could be obtained. Examination of the purified appressoria by transmission
      electron microscopy showed that most had lost their cytoplasm. However, the
      plasma membrane was retained, suggesting that there is some form of attachment of
      this membrane to the cell wall. The purified appressoria can be used for studies
      of their cell surface, and we have shown that there are clear differences in the
      glycoprotein constituents of cell walls of appressoria compared with mycelium.

PMID- 10919808
TI  - Colonization of corn, Zea mays, by the entomopathogenic fungus Beauveria
      bassiana.
AB  - Light and electron microscopy were used to describe the mode of penetration by
      the entomopathogenic fungus Beauveria bassiana (Balsamo) Vuillemin into corn, Zea
      mays L. After inoculation with a foliar spray of conidia, germinating hyphae grew
      randomly across the leaf surface. Often a germ tube formed from a conidium and
      elongated only a short distance before terminating its growth. Not all developing
      hyphae on the leaf surface penetrated the cuticle. However, when penetration did
      occur, the penetration site(s) was randomly located, indicating that B. bassiana
      does not require specific topographic signals at an appropriate entry site as do
      some phytopathogenic fungi. Long hyphal structures were observed to follow the
      leaf apoplast in any direction from the point of penetration. A few hyphae were
      observed within xylem elements. Because vascular bundles are interconnected
      throughout the corn plant, this may explain how B. bassiana travels within the
      plant and ultimately provides overall insecticidal protection. Virulency
      bioassays demonstrate that B. bassiana does not lose virulence toward the
      European corn borer, Ostrinia nubilalis (Hubner), once it colonizes corn. This
      endophytic relationship between an entomopathogenic fungus and a plant suggests
      possibilities for biological control, including the use of indigenous fungal
      inocula as insecticides.

PMID- 10919809
TI  - Cloning of the spoT gene of "Candidatus Phlomobacter fragariae" and development
      of a PCR-restriction fragment length polymorphism assay for detection of the
      bacterium in insects.
AB  - Marginal chlorosis is a new disease of strawberry in which the uncultured phloem
      restricted proteobacterium "Candidatus Phlomobacter fragariae" is involved. In
      order to identify the insect(s) vector(s) of this bacterium, homopteran insects
      have been captured. Because a PCR test based on the 16S rRNA gene (rDNA) applied
      to these insects was unable to discriminate between "P. fragariae" and other
      insect-associated proteobacteria, isolation of "P. fragariae" genes other than
      16S rDNA was undertaken. Using comparative randomly amplified polymorphic DNAs,
      an amplicon was specifically amplified from "P. fragariae"-infected strawberry
      plants. It encodes part of a "P. fragariae" open reading frame sharing
      appreciable homology with the spoT gene from other proteobacteria. A spoT-based
      PCR test combined with restriction fragment length polymorphisms was developed
      and was able to distinguish "P. fragariae" from other insect bacteria. None of
      the many leafhoppers and psyllids captured during several years in and around
      infected strawberry fields was found to carry "P. fragariae." Interestingly
      however, the "P. fragariae" spoT sequence could be easily detected in whiteflies
      proliferating on "P. fragariae"-infected strawberry plants under confined
      greenhouse conditions but not on control whiteflies, indicating that these
      insects can become infected with the bacterium.

PMID- 10919811
TI  - Evaluation of fluorescently labeled lectins for noninvasive localization of
      extracellular polymeric substances in Sphingomonas biofilms.
AB  - Three strains of Sphingomonas were grown as biofilms and tested for binding of
      five fluorescently labeled lectins (Con A-type IV-TRITC or -Cy5, Pha-E-TRITC, PNA
      TRITC, UEA 1-TRITC, and WGA-Texas red). Only ConA and WGA were significantly
      bound by the biofilms. Binding of the five lectins to artificial biofilms made of
      the commercially available Sphingomonas extracellular polysaccharides was similar
      to binding to living biofilms. Staining of the living and artificial biofilms by
      ConA might be explained as binding of the lectin to the terminal mannosyl and
      terminal glucosyl residues in the polysaccharides secreted by Sphingomonas as
      well as to the terminal mannosyl residue in glycosphingolipids. Staining of the
      biofilms by WGA could only be explained as binding to the Sphingomonas
      glycosphingolipid membrane, binding to the cell wall, or nonspecific binding.
      Glycoconjugation of ConA and WGA with the target sugars glucose and N
      acetylglucosamine, respectively, was used as a method for evaluation of the
      specificity of the lectins towards Sphingomonas biofilms and Sphingomonas
      polysaccharides. Our results show that the binding of lectins to biofilms does
      not necessarily prove the presence of specific target sugars in the extracellular
      polymeric substances (EPS) in biofilms. The lectins may bind to non-EPS targets
      or adhere nonspecifically to components of the biofilm matrix.

PMID- 10919810
TI  - Long-chain aldehyde dehydrogenase that participates in n-alkane utilization and
      wax ester synthesis in Acinetobacter sp. strain M-1.
AB  - A long-chain aldehyde dehydrogenase, Ald1, was found in a soluble fraction of
      Acinetobacter sp. strain M-1 cells grown on n-hexadecane as a sole carbon source.
      The gene (ald1) was cloned from the chromosomal DNA of the bacterium. The open
      reading frame of ald1 was 1,512 bp long, corresponding to a protein of 503 amino
      acid residues (molecular mass, 55,496 Da), and the deduced amino acid sequence
      showed high similarity to those of various aldehyde dehydrogenases. The ald1 gene
      was stably expressed in Escherichia coli, and the gene product (recombinant Ald1
      [rAld1]) was purified to apparent homogeneity by gel electrophoresis. rAld1
      showed enzyme activity toward n-alkanals (C(4) to C(14)), with a preference for
      longer carbon chains within the tested range; the highest activity was obtained
      with tetradecanal. The ald1 gene was disrupted by homologous recombination on the
      Acinetobacter genome. Although the ald1 disruptant (ald1Delta) strain still had
      the ability to grow on n-hexadecane to some extent, its aldehyde dehydrogenase
      activity toward n-tetradecanal was reduced to half the level of the wild-type
      strain. Under nitrogen-limiting conditions, the accumulation of intracellular wax
      esters in the ald1Delta strain became much lower than that in the wild-type
      strain. These and other results imply that a soluble long-chain aldehyde
      dehydrogenase indeed plays important roles both in growth on n-alkane and in wax
      ester formation in Acinetobacter sp. strain M-1.

PMID- 10919812
TI  - Degradation of triphenyltin by a fluorescent pseudomonad.
AB  - Triphenyltin (TPT)-degrading bacteria were screened by a simple technique using a
      post-column high-performance liquid chromatography using 3,3',4',7
      tetrahydroxyflavone as a post-column reagent for determination of TPT and its
      metabolite, diphenyltin (DPT). An isolated strain, strain CNR15, was identified
      as Pseudomonas chlororaphis on the basis of its morphological and biochemical
      features. The incubation of strain CNR15 in a medium containing glycerol,
      succinate, and 130 microM TPT resulted in the rapid degradation of TPT and the
      accumulation of approximately 40 microM DPT as the only metabolite after 48 h.
      The culture supernatants of strain CNR15, grown with or without TPT, exhibited a
      TPT degradation activity, whereas the resting cells were not capable of degrading
      TPT. TPT was stoichiometrically degraded to DPT by the solid-phase extract of the
      culture supernatant, and benzene was detected as another degradation product. We
      found that the TPT degradation was catalyzed by low-molecular-mass substances
      (approximately 1,000 Da) in the extract, termed the TPT-degrading factor. The
      other fluorescent pseudomonads, P. chlororaphis ATCC 9446, Pseudomonas
      fluorescens ATCC 13525, and Pseudomonas aeruginosa ATCC 15692, also showed TPT
      degradation activity similar to strain CNR15 in the solid-phase extracts of their
      culture supernatants. These results suggest that the extracellular low-molecular
      mass substance that is universally produced by the fluorescent pseudomonad could
      function as a potent catalyst to cometabolite TPT in the environment.

PMID- 10919813
TI  - Expression of a functional antizearalenone single-chain Fv antibody in transgenic
      Arabidopsis plants.
AB  - The efficacy of cloning a recombinant mycotoxin antibody in plants was tested
      using Arabidopsis as a model. An antizearalenone single-chain Fv (scFv) DNA
      fragment was first cloned in the newly constructed phage display vector (pEY.5)
      and then recloned in the plant transformation vector pKYLX71::35S(2). After
      transformation, constructs of antizearalenone scFv were introduced into immature
      Arabidopsis seeds via Agrobacterium tumefaciens mediation by vacuum infiltration.
      Only plants transformed with the construct containing a PR-1b signal peptide
      sequence produced transgenic offspring. The antizearalenone scFv "plantibody"
      from these transgenic plants bound zearalenone with a high affinity (50%
      inhibitory concentration, 11.2 ng/ml) that was comparable to that of bacterially
      produced scFv antibody and the parent monoclonal antibody (MAb). By electron
      microscopic immunogold labeling, the presence of antizearalenone scFv was
      detected mainly in the cytoplasm and only occasionally outside the cell. Like
      bacterially produced scFv antibody, antizearalenone scFv plantibody exhibited
      greater sensitivity to methanol destabilization than did the parent MAb. The
      sensitivity of antizearalenone scFv plantibody to acidic disassociation was
      similar to the sensitivities of bacterially produced scFv antibody and MAb.
      Expression of specific plantibodies in crops might be useful for neutralizing
      mycotoxins in animal feeds and for reducing mycotoxin-associated plant diseases.

PMID- 10919815
TI  - Lipopolysaccharides of Rhizobium etli strain G12 act in potato roots as an
      inducing agent of systemic resistance to infection by the cyst nematode Globodera
      pallida.
AB  - Recent studies have shown that living and heat-killed cells of the rhizobacterium
      Rhizobium etli strain G12 induce in potato roots systemic resistance to infection
      by the potato cyst nematode Globodera pallida. To better understand the
      mechanisms of induced resistance, we focused on identifying the inducing agent.
      Since heat-stable bacterial surface carbohydrates such as exopolysaccharides
      (EPS) and lipopolysaccharides (LPS) are essential for recognition in the
      symbiotic interaction between Rhizobium and legumes, their role in the R. etli
      potato interaction was studied. EPS and LPS were extracted from bacterial
      cultures, applied to potato roots, and tested for activity as an inducer of plant
      resistance to the plant-parasitic nematode. Whereas EPS did not affect G. pallida
      infection, LPS reduced nematode infection significantly in concentrations as low
      as 1 and 0.1 mg ml(-1). Split-root experiments, guaranteeing a spatial separation
      of inducing agent and challenging pathogen, showed that soil treatments of one
      half of the root system with LPS resulted in a highly significant (up to 37%)
      systemic induced reduction of G. pallida infection of potato roots in the other
      half. The results clearly showed that LPS of R. etli G12 act as the inducing
      agent of systemic resistance in potato roots.

PMID- 10919814
TI  - Analysis of gyrB and toxR gene sequences of Vibrio hollisae and development of
      gyrB- and toxR-targeted PCR methods for isolation of V. hollisae from the
      environment and its identification.
AB  - Isolation of Vibrio hollisae strains, particularly from the environment, is rare.
      This may be due, in part, to the difficulty encountered when using conventional
      biochemical tests to identify the microorganism. In this study, we evaluated
      whether two particular genes may be useful for the identification of V. hollisae.
      The two genes are presumed to be conserved among the bacterial species (gyrB) or
      among the species of the genus Vibrio (toxR). A portion of the gyrB sequence of
      V. hollisae was cloned by PCR using a set of degenerate primers. The sequence
      showed 80% identity with the corresponding Vibrio parahaemolyticus gyrB sequence.
      The toxR gene of V. hollisae was cloned utilizing a htpG gene probe derived from
      the V. parahaemolyticus htpG gene, which is known to be linked to the toxR gene
      in V. hollisae. The coding sequence of the cloned V. hollisae toxR gene had 59%
      identity with the V. parahaemolyticus toxR coding sequence. The results of DNA
      colony hybridization tests using the DNA probes derived from the two genes of V.
      hollisae indicated that these gene sequences could be utilized for
      differentiation of V. hollisae from other Vibrio species and from microorganisms
      found in marine fish. PCR methods targeting the two gene sequences were
      established. Both PCR methods were shown to specifically detect the respective
      target sequences of V. hollisae but not other organisms. A strain of V. hollisae
      added at a concentration of 1 to 10(2) CFU/ml to alkaline peptone water
      containing a seafood sample could be detected by a 4-h enrichment incubation in
      alkaline peptone water at 37 degrees C followed by quick DNA extraction with an
      extraction kit and 35-cycle PCR specific for the V. hollisae toxR gene. We
      conclude that screening of seafood samples by this 35-cycle, V. hollisae toxR
      specific PCR, followed by isolation on a differential medium and identification
      by the above htpG- and toxR-targeted PCR methods, can be useful for isolation
      from the environment and identification of V. hollisae.

PMID- 10919816
TI  - Correlation of activities of the enzymes alpha-phosphoglucomutase, UDP-galactose
      4-epimerase, and UDP-glucose pyrophosphorylase with exopolysaccharide
      biosynthesis by Streptococcus thermophilus LY03.
AB  - The effects of different carbohydrates or mixtures of carbohydrates as substrates
      on bacterial growth and exopolysaccharide (EPS) production were studied for the
      yoghurt starter culture Streptococcus thermophilus LY03. This strain produces two
      heteropolysaccharides with the same monomeric composition (galactose and glucose
      in the ratio 4:1) but with different molecular masses. Lactose and glucose were
      fermented by S. thermophilus LY03 only when they were used as sole energy and
      carbohydrate sources. Fructose was also fermented when it was applied in
      combination with lactose or glucose. Both the amount of EPS produced and the
      carbohydrate source consumption rates were clearly influenced by the type of
      energy and carbohydrate source used, while the EPS monomeric composition remained
      constant (galactose-glucose, 4:1) under all circumstances. A combination of
      lactose and glucose resulted in the largest amounts of EPS. Measurements of the
      activities of enzymes involved in EPS biosynthesis, and of those involved in
      sugar nucleotide biosynthesis and the Embden-Meyerhof-Parnas pathway,
      demonstrated that the levels of activity of alpha-phosphoglucomutase, UDP
      galactose 4-epimerase, and UDP-glucose pyrophosphorylase are highly correlated
      with the amount of EPS produced. Furthermore, a weaker relationship or no
      relationship between the amounts of EPS and the enzymes involved in either the
      rhamnose nucleotide synthetic branch of the EPS biosynthesis or the pathway
      leading to glycolysis was observed for S. thermophilus LY03.

PMID- 10919817
TI  - Applicability of an Arrhenius model for the combined effect of temperature and
      CO(2) packaging on the spoilage microflora of fish.
AB  - The temperature behavior of the natural microflora on the Mediterranean fish red
      mullet (Mullus barbatus) was examined as a case study. The growth of the spoilage
      bacteria Pseudomonas spp., Shewanella putrefaciens, Brochothrix thermosphacta,
      and lactic acid bacteria was modeled as a function of temperature and the
      concentration of carbon dioxide in modified atmosphere packaging. Combined models
      were developed and comparatively assessed based on polynomial, Belehradek, and
      Arrhenius equations. The activation energy parameter of the Arrhenius model,
      E(A), was independent of the packaging atmosphere and ranged from 75 to 85 kJ/mol
      for the different bacteria, whereas the preexponential constant decreased
      exponentially with the packaging CO(2) concentration. We evaluated the
      applicability of the models developed by using experimental bacterial growth
      rates obtained from 42 independent experiments performed with three Mediterranean
      fish species and growth rates predicted from the models under the same
      temperature and packaging conditions. The accuracy factor and bias factor were
      used as statistical tools for evaluation, and the developed Arrhenius model and
      the Belehradek model were judged satisfactory overall.

PMID- 10919818
TI  - Characterization of an isolate that uses vinyl chloride as a growth substrate
      under aerobic conditions.
AB  - An aerobic enrichment culture was developed by using vinyl chloride (VC) as the
      sole organic carbon and electron donor source. VC concentrations as high as 7.3
      mM were biodegraded without apparent inhibition. VC use did not occur when
      nitrate was provided as the electron acceptor. A gram-negative, rod-shaped,
      motile isolate was obtained from the enrichment culture and identified based on
      biochemical characteristics and the sequence of its 16S rRNA gene as Pseudomonas
      aeruginosa, designated strain MF1. The observed yield of MF1 when it was grown on
      VC was 0.20 mg of total suspended solids (TSS)/mg of VC. Ethene, acetate,
      glyoxylate, and glycolate also served as growth substrates, while ethane,
      chloroacetate, glycolaldehyde, and phenol did not. Stoichiometric release of
      chloride and minimal accumulation of soluble metabolites following VC consumption
      indicated that the predominant fate for VC is mineralization and incorporation
      into cell material. MF1 resumed consumption of VC after at least 24 days when
      none was provided, unlike various mycobacteria that lost their VC-degrading
      ability after brief periods in the absence of VC. When deprived of oxygen for 2.5
      days, MF1 did not regain the ability to grow on VC, and a portion of the VC was
      transformed into VC-epoxide. Acetylene inhibited VC consumption by MF1,
      suggesting the involvement of a monooxygenase in the initial step of VC
      metabolism. The maximum specific VC utilization rate for MF1 was 0.41 micromol of
      VC/mg of TSS/day, the maximum specific growth rate was 0.0048/day, and the Monod
      half-saturation coefficient was 0.26 microM. A higher yield and faster kinetics
      occurred when MF1 grew on ethene. When grown on ethene, MF1 was able to switch to
      VC as a substrate without a lag. It therefore appears feasible to grow MF1 on a
      nontoxic substrate and then apply it to environments that do not exhibit a
      capacity for aerobic biodegradation of VC.

PMID- 10919819
TI  - Heterologous coproduction of enterocin A and pediocin PA-1 by Lactococcus lactis:
      detection by specific peptide-directed antibodies.
AB  - Antibodies against enterocin A were obtained by immunization of rabbits with
      synthetic peptides PH4 and PH5 designed, respectively, on the N- and C-terminal
      amino acid sequences of enterocin A and conjugated to the carrier protein KLH.
      Anti-PH4-KLH antibodies not only recognized enterocin A but also pediocin PA-1,
      enterocin P, and sakacin A, three bacteriocins which share the N-terminal class
      IIa consensus motif (YGNGVXC) that is contained in the sequence of the peptide
      PH4. In contrast, anti-PH5-KLH antibodies only reacted with enterocin A because
      the amino acid sequences of the C-terminal parts of class IIa bacteriocins are
      highly variable. Enterocin A and/or pediocin PA-1 structural and immunity genes
      were introduced in Lactococcus lactis IL1403 to achieve (co)production of the
      bacteriocins. The level of production of the two bacteriocins was significantly
      lower than that obtained by the wild-type producers, a fact that suggests a low
      efficiency of transport and/or maturation of these bacteriocins by the
      chromosomally encoded bacteriocin translocation machinery of IL1403. Despite the
      low production levels, both bacteriocins could be specifically detected and
      quantified with the anti-PH5-KLH (anti-enterocin A) antibodies isolated in this
      study and the anti-PH2-KLH (anti-pediocin PA-1) antibodies previously generated
      (J. M. Martinez, M. I. Martinez, A. M. Suarez, C. Herranz, P. Casaus, L. M.
      Cintas, J. M. Rodriguez, and P. E. Hernandez, Appl. Environ. Microbiol. 64:4536
      4545, 1998). In this work, the availability of antibodies for the specific
      detection and quantification of enterocin A and pediocin PA-1 was crucial to
      demonstrate coproduction of both bacteriocins by L. lactis IL1403(pJM04), because
      indicator strains that are selectively inhibited by each bacteriocin are not
      available.

PMID- 10919820
TI  - Temperature affects species distribution in symbiotic populations of Vibrio spp.
AB  - The genus Sepiola (Cephalopoda: Sepiolidae) contains 10 known species that occur
      in the Mediterranean Sea today. All Sepiola species have a light organ that
      contains at least one of two species of luminous bacteria, Vibrio fischeri and
      Vibrio logei. The two Vibrio species coexist in at least four Sepiola species (S.
      affinis, S. intermedia, S. ligulata, and S. robusta), and their concentrations in
      the light organ depend on changes in certain abiotic factors, including
      temperature. Strains of V. fischeri grew faster in vitro and in Sepiola juveniles
      when they were incubated at 26 degrees C. In contrast, strains of V. logei grew
      faster at 18 degrees C in culture and in Sepiola juveniles. When aposymbiotic S.
      affinis or S. ligulata juveniles were inoculated with one Vibrio species, all
      strains of V. fischeri and V. logei were capable of infecting both squid species
      at the optimum growth temperatures, regardless of the squid host from which the
      bacteria were initially isolated. However, when two different strains of V.
      fischeri and V. logei were placed in direct competition with each other at either
      18 or 26 degrees C, strains of V. fischeri were present in sepiolid light organs
      in greater concentrations at 26 degrees C, whereas strains of V. logei were
      present in greater concentrations at 18 degrees C. In addition to the competition
      experiments, the ratios of the two bacterial species in adult Sepiola specimens
      caught throughout the season at various depths differed, and these differences
      were correlated with the temperature in the surrounding environment. My findings
      contribute additional data concerning the ecological and environmental factors
      that affect host-symbiont recognition and may provide insight into the evolution
      of animal-bacterium specificity.

PMID- 10919822
TI  - Differentiation of chitinase-active and non-chitinase-active subpopulations of a
      marine bacterium during chitin degradation.
AB  - The ability of marine bacteria to adhere to detrital particulate organic matter
      and rapidly switch on metabolic genes in an effort to reproduce is an important
      response for bacterial survival in the pelagic marine environment. The goal of
      this investigation was to evaluate the relationship between chitinolytic gene
      expression and extracellular chitinase activity in individual cells of the marine
      bacterium Pseudoalteromonas sp. strain S91 attached to solid chitin. A green
      fluorescent protein reporter gene under the control of the chiA promoter was used
      to evaluate chiA gene expression, and a precipitating enzyme-linked fluorescent
      probe, ELF-97-N-acetyl-beta-D-glucosaminide, was used to evaluate extracellular
      chitinase activity among cells in the bacterial population. Evaluation of chiA
      expression and ELF-97 crystal location at the single-cell level revealed two
      physiologically distinct subpopulations of S91 on the chitin surface: one that
      was chitinase active and remained associated with the surface and another that
      was non-chitinase active and released daughter cells into the bulk aqueous phase.
      It is hypothesized that the surface-associated, non-chitinase-active population
      is utilizing chitin degradation products that were released by the adjacent
      chitinase-active population for cell replication and dissemination into the bulk
      aqueous phase.

PMID- 10919821
TI  - Effect of field inoculation with Sinorhizobium meliloti L33 on the composition of
      bacterial communities in rhizospheres of a target plant (Medicago sativa) and a
      non-target plant (Chenopodium album)-linking of 16S rRNA gene-based single-strand
      conformation polymorphism community profiles to the diversity of cultivated
      bacteria.
AB  - Fourteen weeks after field release of luciferase gene-tagged Sinorhizobium
      meliloti L33 in field plots seeded with Medicago sativa, we found that the
      inoculant also occurred in bulk soil from noninoculated control plots. In
      rhizospheres of M. sativa plants, S. meliloti L33 could be detected in
      noninoculated plots 12 weeks after inoculation, indicating that growth in the
      rhizosphere preceded spread into bulk soil. To determine whether inoculation
      affected bacterial diversity, 1,119 bacteria were isolated from the rhizospheres
      of M. sativa and Chenopodium album, which was the dominant weed in the field
      plots. Amplified ribosomal DNA restriction analysis (ARDRA) revealed plant
      specific fragment size frequencies. Dominant ARDRA groups were identified by 16S
      rRNA gene nucleotide sequencing. Database comparisons indicated that the
      rhizospheres contained members of the Proteobacteria (alpha, beta, and gamma
      subgroups), members of the Cytophaga-Flavobacterium group, and gram-positive
      bacteria with high G+C DNA contents. The levels of many groups were affected by
      the plant species and, in the case of M. sativa, by inoculation. The most
      abundant isolates were related to Variovorax sp., Arthrobacter ramosus, and
      Acinetobacter calcoaceticus. In the rhizosphere of M. sativa, inoculation reduced
      the numbers of cells of A. calcoaceticus and members of the genus Pseudomonas and
      increased the number of rhizobia. Cultivation-independent PCR-single-strand
      conformation polymorphism (SSCP) profiles of a 16S rRNA gene region confirmed the
      existence of plant-specific rhizosphere communities and the effect of the
      inoculant. All dominant ARDRA groups except Variovorax species could be detected.
      On the other hand, the SSCP profiles revealed products which could not be
      assigned to the dominant cultured isolates, indicating that the bacterial
      diversity was greater than the diversity suggested by cultivation.

PMID- 10919823
TI  - Spatial and temporal variations in chitinolytic gene expression and bacterial
      biomass production during chitin degradation.
AB  - Growth of the chitin-degrading marine bacterium S91 on solid surfaces under
      oligotrophic conditions was accompanied by the displacement of a large fraction
      of the surface-derived bacterial production into the flowing bulk aqueous phase,
      irrespective of the value of the surface as a nutrient source. Over a 200-h
      period of surface colonization, 97 and 75% of the bacterial biomass generated on
      biodegradable chitin and a nonnutritional silicon surface, respectively, detached
      to become part of the free-living population in the bulk aqueous phase. Specific
      surface-associated growth rates that included the cells that subsequently
      detached from the substrata varied depending on the nutritional value of the
      substratum and during the period of surface colonization. Specific growth rates
      of 3.79 and 2.83 day(-1) were obtained when cells first began to proliferate on a
      pure chitin film and a silicon surface, respectively. Later, when cell densities
      on the surface and detached cells as CFU in the bulk aqueous phase achieved a
      quasi-steady state, specific growth rates decreased to 1.08 and 0.79 day(-1) on
      the chitin and silicon surfaces, respectively. Virtually all of the cells that
      detached from either the chitin or the silicon surfaces and the majority of cells
      associated with the chitin surface over the 200-h period of surface colonization
      displayed no detectable expression of the chitin-degrading genes chiA and chiB.
      Cells displaying high levels of chiA-chiB expression were detected only on the
      chitin surface and then only clustered in discrete areas of the surface. Surface
      associated, differential gene expression and displacement of bacterial production
      from surfaces represent adaptations at the population level that promote
      efficient utilization of limited resources and dispersal of progeny to maximize
      access to new sources of energy and maintenance of the population.

PMID- 10919824
TI  - Real-time measurements of the interaction between single cells of Listeria
      monocytogenes and nisin on a solid surface.
AB  - A method to obtain real-time measurements of the interactions between nisin and
      single cells of Listeria monocytogenes on a solid surface was developed. This
      method was based on fluorescence ratio-imaging microscopy and measurements of
      changes in the intracellular pH (pH(i)) of carboxyfluorescein succinimidyl ester
      stained cells during exposure to nisin. Immobilized cells were placed in a
      chamber mounted on a microscope and attached to a high-precision peristaltic pump
      which allowed rapid changes in the nisin concentration. In the absence of nisin,
      the pH(i) of L. monocytogenes was almost constant (approximately pH 8.0) and
      independent of the external pH in the pH range from 5.0 to 9.0. In the presence
      of nisin, dissipation of the pH gradient (DeltapH) was observed, and this
      dissipation was both time and nisin concentration dependent. The dissipation of
      DeltapH resulted in cell death, as determined by the number of CFU. In the model
      system which we used the immobilized cells were significantly more resistant to
      nisin than the planktonic cells. The kinetics of DeltapH dissipation for single
      cells revealed a variable lag phase depending on the nisin concentration, which
      was followed by a very rapid decrease in pH(i) within 1 to 2 min. The differences
      in nisin sensitivity between single cells in a L. monocytogenes population were
      insignificant for cells grown to the stationary phase in a liquid laboratory
      substrate, but differences were observed for cells grown on an agar medium under
      similar conditions, which resulted in some cells having increased resistance to
      nisin.

PMID- 10919825
TI  - Community structure, cellular rRNA content, and activity of sulfate-reducing
      bacteria in marine arctic sediments.
AB  - The community structure of sulfate-reducing bacteria (SRB) of a marine Arctic
      sediment (Smeerenburgfjorden, Svalbard) was characterized by both fluorescence in
      situ hybridization (FISH) and rRNA slot blot hybridization by using group- and
      genus-specific 16S rRNA-targeted oligonucleotide probes. The SRB community was
      dominated by members of the Desulfosarcina-Desulfococcus group. This group
      accounted for up to 73% of the SRB detected and up to 70% of the SRB rRNA
      detected. The predominance was shown to be a common feature for different
      stations along the coast of Svalbard. In a top-to-bottom approach we aimed to
      further resolve the composition of this large group of SRB by using probes for
      cultivated genera. While this approach failed, directed cloning of probe-targeted
      genes encoding 16S rRNA was successful and resulted in sequences which were all
      affiliated with the Desulfosarcina-Desulfococcus group. A group of clone
      sequences (group SVAL1) most closely related to Desulfosarcina variabilis (91.2%
      sequence similarity) was dominant and was shown to be most abundant in situ,
      accounting for up to 54. 8% of the total SRB detected. A comparison of the two
      methods used for quantification showed that FISH and rRNA slot blot hybridization
      gave comparable results. Furthermore, a combination of the two methods allowed us
      to calculate specific cellular rRNA contents with respect to localization in the
      sediment profile. The rRNA contents of Desulfosarcina-Desulfococcus cells were
      highest in the first 5 mm of the sediment (0.9 and 1.4 fg, respectively) and
      decreased steeply with depth, indicating that maximal metabolic activity occurred
      close to the surface. Based on SRB cell numbers, cellular sulfate reduction rates
      were calculated. The rates were highest in the surface layer (0.14 fmol cell(-1)
      day(-1)), decreased by a factor of 3 within the first 2 cm, and were relatively
      constant in deeper layers.

PMID- 10919826
TI  - Unlabeled helper oligonucleotides increase the in situ accessibility to 16S rRNA
      of fluorescently labeled oligonucleotide probes.
AB  - Target site inaccessibility represents a significant problem for fluorescence in
      situ hybridization (FISH) of 16S rRNA with oligonucleotide probes. Here,
      unlabeled oligonucleotides (helpers) that bind adjacent to the probe target site
      were evaluated for their potential to increase weak probe hybridization signals
      in Escherichia coli DSM 30083(T). The use of helpers enhanced the fluorescence
      signal of all six probes examined at least fourfold. In one case, the signal of
      probe Eco474 was increased 25-fold with the use of a single helper probe, H440-2.
      In another case, four unlabeled helpers raised the FISH signal of a formerly weak
      probe, Eco585, to the level of the brightest monolabeled oligonucleotide probes
      available for E. coli. The temperature of dissociation and the mismatch
      discrimination of probes were not significantly influenced by the addition of
      helpers. Therefore, using helpers should not cause labeling of additional
      nontarget organisms at a defined stringency of hybridization. However, the helper
      action is based on sequence-specific binding, and there is thus a potential for
      narrowing the target group which must be considered when designing helpers. We
      conclude that helpers can open inaccessible rRNA regions for FISH with
      oligonucleotide probes and will thereby further improve the applicability of this
      technique for in situ identification of microorganisms.

PMID- 10919827
TI  - Cultivation and in situ detection of a thermophilic bacterium capable of
      oxidizing propionate in syntrophic association with hydrogenotrophic methanogens
      in a thermophilic methanogenic granular sludge.
AB  - The thermophilic, anaerobic, propionate-oxidizing bacterial populations present
      in the methanogenic granular sludge in a thermophilic (55 degrees C) upflow
      anaerobic sludge blanket reactor were studied by cultivation and in situ
      hybridization analysis. For isolation of propionate-degrading microbes, primary
      enrichment was made with propionate as the sole energy source at 55 degrees C.
      After several attempts to purify the microbes, a thermophilic, syntrophic,
      propionate-oxidizing bacterium, designated strain SI, was isolated in both pure
      culture and coculture with Methanobacterium thermoautotrophicum. Under
      thermophilic (55 degrees C) conditions, strain SI oxidized propionate, ethanol,
      and lactate in coculture with M. thermoautotrophicum. In pure culture, the
      isolate was found to ferment pyruvate. 16S ribosomal DNA sequence analysis
      revealed that the strain was relatively close to members of the genus
      Desulfotomaculum, but it was only distantly related to any known species. To
      elucidate the abundance and spatial distribution of organisms of the strain SI
      type within the sludge granules, a 16S rRNA-targeted oligonucleotide probe
      specific for strain SI was developed and applied to thin sections of the
      granules. Fluorescence in situ hybridization combined with confocal laser
      scanning microscopy revealed that a number of rod-shaped cells were present in
      the middle and inner layers of the thermophilic granule sections and that they
      formed close associations with hydrogenotrophic methanogens. They accounted for
      approximately 1.1% of the total cells in the sludge. These results demonstrated
      that strain SI was one of the significant populations in the granular sludge and
      that it was responsible for propionate oxidation in the methanogenic granular
      sludge in the reactor.

PMID- 10919829
TI  - PCR use of highly conserved DNA regions for identification of Sinorhizobium
      meliloti.
AB  - A PCR identification method in which four primers that recognize homologous
      conserved regions in the Sinorhizobium meliloti genome are used was developed and
      tested. The regions used for identification were the nodbox 4 locus, which is
      located in one of the symbiotic megaplasmids, and the mucR gene, which is located
      in the chromosome. The new method was used to establish a collection of S.
      meliloti strains from polluted soils.

PMID- 10919828
TI  - Terminal restriction fragment length polymorphism analysis program, a web-based
      research tool for microbial community analysis.
AB  - Rapid analysis of microbial communities has proven to be a difficult task. This
      is due, in part, to both the tremendous diversity of the microbial world and the
      high complexity of many microbial communities. Several techniques for community
      analysis have emerged over the past decade, and most take advantage of the
      molecular phylogeny derived from 16S rRNA comparative sequence analysis. We
      describe a web-based research tool located at the Ribosomal Database Project web
      site (http://www.cme.msu.edu/RDP/html/analyses. html) that facilitates microbial
      community analysis using terminal restriction fragment length polymorphism of 16S
      ribosomal DNA. The analysis function (designated TAP T-RFLP) permits the user to
      perform in silico restriction digestions of the entire 16S sequence database and
      derive terminal restriction fragment sizes, measured in base pairs, from the 5'
      terminus of the user-specified primer to the 3' terminus of the restriction
      endonuclease target site. The output can be sorted and viewed either
      phylogenetically or by size. It is anticipated that the site will guide
      experimental design as well as provide insight into interpreting results of
      community analysis with terminal restriction fragment length polymorphisms.

PMID- 10919830
TI  - Production of Poly(3-hydroxybutyrate) by fed-batch culture of recombinant
      Escherichia coli with a highly concentrated whey solution.
AB  - Fermentation strategies for the production of poly(3-hydroxybutyrate) (PHB) from
      whey by recombinant Escherichia coli strain CGSC 4401 harboring the Alcaligenes
      latus polyhydroxyalkanoate (PHA) biosynthesis genes were developed. The pH-stat
      fed-batch cultures of E. coli CGSC 4401 harboring pJC4, a stable plasmid
      containing the A. latus PHA biosynthesis genes, were carried out with a
      concentrated whey solution containing 280 g of lactose equivalent per liter.
      Final cell and PHB concentrations of 119.5 and 96.2 g/liter, respectively, were
      obtained in 37.5 h, which resulted in PHB productivity of 2.57 g/liter/h.

PMID- 10919831
TI  - Evaluation of immunomagnetic separation for recovery of Cryptosporidium parvum
      and Giardia duodenalis from high-iron matrices.
AB  - In this study we examined the recovery of Cryptosporidium parvum and Giardia
      duodenalis from matrices containing various concentrations of dissolved iron. The
      organisms were recovered by using the immunomagnetic separation-immunofluorescent
      assay method, and the levels of recovery were compared to the dissolved iron
      concentrations. The levels of recovery of C. parvum decreased sharply at
      dissolved iron concentrations greater than 4 mg/liter, while the levels of
      recovery of G. duodenalis decreased sharply at concentrations greater than 40
      mg/liter.

PMID- 10919833
TI  - Isolation of mycobacteria from frozen fish destined for human consumption.
AB  - Mycobacteria were isolated from defrost water and tissue of sole (Solea solea),
      hake (Merluccius merluccius), cod (Gadus morhua), ling (Genypterus blacodes), and
      monkfish (Lophius piscatorius) on Lowenstein-Jensen medium after incubation at
      different temperatures. Samples of frozen fish were obtained under sterile
      conditions inside a refrigeration chamber (-18 to -22 degrees C) in a wholesale
      market from which these products are distributed to shops for retail sale and
      human consumption.

PMID- 10919832
TI  - A simple, rapid method for demonstrating bacterial flagella.
AB  - We developed a simple, rapid method for demonstrating flagellation of bacteria
      using the fluorescent protein stain NanoOrange (Molecular Probes, Eugene, Oreg.).
      The NanoOrange reagent binds to hydrophobic regions of proteins, which results in
      substantial enhancement of fluorescence. Unbound reagent is essentially
      nonfluorescent. NanoOrange fluorescently stained bacterial cell bodies, as well
      as flagella and other appendages, which could be directly observed by
      epifluorescence microscopy. Detection of flagella was further improved by using a
      charge-coupled device camera for image capture and processing. The reliability of
      the method was tested by using 37 pure cultures of marine bacteria. Detection of
      flagella on the isolates by NanoOrange staining was compared to detection by
      transmission electron microscopy (TEM). For 36 of 37 cultures, the two methods
      yielded the same results. In one case, flagella were detected by TEM but not by
      NanoOrange, although the difference may be attributable to differences between
      the culture preparations. NanoOrange staining is rapid (10 to 15 min) and does
      not require fixation or dehydration, so live samples can be stained. Since
      NanoOrange is a general protein stain and works directly in seawater, it may also
      prove to be useful for staining other proteinaceous material that is of interest
      to aquatic microbial ecologists.

PMID- 10919834
TI  - Mycophenolic acid in silage.
AB  - We examined 233 silage samples and found that molds were present in 206 samples
      with counts between 1 x 10(3) and 8.9 x 10(7) (mean, 4.7 x 10(6)) CFU/g.
      Mycophenolic acid, a metabolite of Penicillium roqueforti, was detected by liquid
      chromatography-mass spectrometry in 74 (32%) of these samples at levels ranging
      from 20 to 35,000 (mean, 1,400) microg/kg. This compound has well-known
      immunosuppressive properties, so feeding with contaminated silage may promote the
      development of infectious diseases in livestock.

PMID- 10919835
TI  - marY1, a member of the gypsy group of long terminal repeat retroelements from the
      ectomycorrhizal basidiomycete Tricholoma matsutake.
AB  - We cloned an intact copy of a long terminal repeat retroelement designated marY1
      from the ectomycorrhizal basidiomycete Tricholoma matsutake. The reverse
      transcriptase domain is found in T. matsutake and Tricholoma magnivelare
      worldwide. This finding suggests that retroelements associate with
      ectomycorrhizal basidiomycetes and may be useful as genetic markers for
      identification, phylogenetic analysis, and mutagenesis of this fungal group.

PMID- 10919836
TI  - Transformation of amoxapine by Cunninghamella elegans.
AB  - We examined Cunninghamella elegans to determine its ability to transform
      amoxapine, a tricyclic antidepressant belonging to the dibenzoxazepine class of
      drugs. Approximately 57% of the exogenous amoxapine was metabolized to three
      metabolites that were isolated by high-performance liquid chromatography and were
      identified by nuclear magnetic resonance and mass spectrometry as 7
      hydroxyamoxapine (48%), N-formyl-7-hydroxyamoxapine (31%), and N-formylamoxapine
      (21%). 7-Hydroxyamoxapine, a mammalian metabolite with biological activity, now
      can be produced in milligram quantities for toxicological evaluation.

PMID- 10919837
TI  - Thiosulfate disproportionation by Desulfotomaculum thermobenzoicum.
AB  - Desulfotomaculum thermobenzoicum, but not Desulfotomaculum nigrificans,
      Desulfotomaculum ruminis, or Desulfosporosinus orientis, grew by
      disproportionation of thiosulfate, forming stoichiometric amounts of sulfate and
      sulfide; sulfite was not disproportionated. The addition of acetate enhanced
      growth and thiosulfate disproportionation by D. thermobenzoicum compared to those
      observed with thiosulfate alone.

PMID- 10919838
TI  - Chlamydophila abortus in a Brown skua (Catharacta antarctica lonnbergi) from a
      subantarctic island.
AB  - On Bird Island, South Georgia, a new strain of Chlamydophila abortus was detected
      in one Brown skua out of 37 specimens from six different seabird species.
      Phylogenetic analysis of the rnpB and omp1 genes indicated the strain to be more
      closely related to C. abortus than to 6BC, the type strain of Chlamydophila
      psittaci.

PMID- 10919839
TI  - Molecular chaperones in the kidney: distribution, putative roles, and regulation.
AB  - Molecular chaperones are intracellular proteins that prevent inappropriate intra-
      and intermolecular interactions of polypetide chains. A specific group of highly
      conserved molecular chaperones are the heat shock proteins (HSPs), many of which
      are constitutively expressed but most of which are inducible by diverse (in some
      cases specific) stress factors. HSPs, either alone or in cooperation with
      "partner" chaperones, are involved in cellular processes as disparate as correct
      folding and assembly of proteins, transport of proteins to specific intracellular
      locations, protein degradation, and preservation and restructuring of the
      cytoskeleton. The characteristic distribution of individual HSPs in the kidney,
      and their response to different challenges, suggests that a number of HSPs may
      fulfill specific, kidney-related functions. HSP72 and the osmotic stress protein
      94 (Osp94) appear to participate in the adaptation of medullary cells to high
      extracellular salt and urea concentrations; the small HSPs (HSP25/27 and
      crystallins) may be involved in the function of mesangial cells and podocytes and
      contribute to the volume-regulatory remodeling of the cytoskeleton in medullary
      cells during changes in extracellular tonicity. HSP90 contributes critically to
      the maturation of steroid hormone receptors and may thus be a critical
      determinant of the aldosterone sensitivity of specific renal epithelial cells.
      Certain HSPs are also induced in various pathological states of the kidney. The
      observation that the expression of individual HSPs in specific kidney diseases
      often displays characteristic time courses and intrarenal distribution patterns
      supports the idea that HSPs are involved in the recovery but possibly also in the
      initiation and/or maintenance phases of these disturbances.

PMID- 10919840
TI  - Molecular pharmacology of renal organic anion transporters.
AB  - Renal organic anion transport systems play an important role in the elimination
      of drugs, toxic compounds, and their metabolites, many of which are potentially
      harmful to the body. The renal proximal tubule is the primary site of carrier
      mediated transport from blood to urine of a wide variety of anionic substrates.
      Recent studies have shown that organic anion secretion in renal proximal tubule
      is mediated by distinct sodium-dependent and sodium-independent transport
      systems. Knowledge of the molecular identity of these transporters and their
      substrate specificity has increased considerably in the past few years by cloning
      of various carrier proteins. However, a number of fundamental questions still
      have to be answered to elucidate the participation of the cloned transporters in
      the overall tubular secretion of anionic xenobiotics. This review summarizes the
      latest knowledge on molecular and pharmacological properties of renal organic
      anion transporters and homologs, with special reference to their nephron and
      plasma membrane localization, transport characteristics, and substrate and
      inhibitor specificity. A number of the recently cloned transporters, such as the
      p-aminohippurate/dicarboxylate exchanger OAT1, the anion/sulfate exchanger SAT1,
      the peptide transporters PEPT1 and PEPT2, and the nucleoside transporters CNT1
      and CNT2, are key proteins in organic anion handling that possess the same
      characteristics as has been predicted from previous physiological studies. The
      role of other cloned transporters, such as MRP1, MRP2, OATP1, OAT-K1, and OAT-K2,
      is still poorly characterized, whereas the only information that is available on
      the homologs OAT2, OAT3, OATP3, and MRP3-6 is that they are expressed in the
      kidney, but their localization, not to mention their function, remains to be
      elucidated.

PMID- 10919841
TI  - Integrins in kidney development, function, and disease.
AB  - Integrins are heterodimeric cell surface receptors that mediate heterophilic cell
      cell interactions and interactions between cells and the extracellular matrix
      (Hynes RO. Cell 69: 11-25, 1991). As such, they are involved in morphogenetic
      processes during development, as well as in the maintenance of normal tissue
      architecture in fully developed organs. Integrins are now recognized to be a
      large family of receptors, and several different integrins have been demonstrated
      as being expressed in the developing and adult kidney (Korhonen M, Ylkanne J,
      Laitinen L, and Virtanen I. Development 122: 3537-3547, 1996; Rahilly MA and
      Fleming S. J Pathol 167: 327-334, 1992). This review will summarize present
      knowledge about integrin expression in the developing, normal, and diseased
      kidney and attempt to provide a hypothetical framework for understanding integrin
      function in the urogenital system. Since the last time this area was reviewed
      (Hamerski DA and Santoro S. Curr Opin Nephrol Hypertens 8: 9-14, 1999), there
      have been significant publications on the roles of integrins in kidney
      development and disease. At present, there are many more questions than answers,
      and integrins present an area where many novel and exciting findings will emerge
      in the coming years.

PMID- 10919842
TI  - Nitric oxide modulates mechanical strain-induced activation of p38 MAPK in
      mesangial cells.
AB  - Mesangial cells (MC), grown on extracellular matrix (ECM) protein-coated plates
      and stretched, proliferate and produce ECM, recapitulating in vivo responses to
      increased glomerular capillary pressure (Pgc). Transduction of strain involves
      mitogen-activated protein kinases (MAPK), and we have shown that p38 MAPK is
      activated by strain in MC. Because in vivo studies show that nitric oxide (NO) in
      the remnant kidney limits glomerular injury without reducing Pgc, we studied
      whether NO attenuated stretch-induced p38 activation in MC. Increasing p38
      activation occurred with increasing stretch, maximally at 10 min at -27-kPa
      vacuum. Cyclic strain increased nuclear translocation of phosphorylated p38 by
      immunofluorescent microscopy and nuclear protein binding to nuclear factor-kappaB
      (NF-kappaB) consensus sequences by mobility shift assay. Both events were largely
      abrogated by the p38 inhibitor SB-203580. The NO donors 3-morpholinosydnonimine,
      S-nitroso-N-acetylpenicillamine, and 8-bromoguanosine 3',5'-cyclic monophosphate,
      a stable cGMP analog, prevented p38 activation and nuclear translocation. Thus
      strain induces p38 activity and translocation to the nucleus and p38-dependent
      increases in nuclear protein binding to NF-kappaB. This pathway is attenuated by
      the NO donors or a cGMP analog.

PMID- 10919843
TI  - Differential subcellular localization of ENaC subunits in mouse kidney in
      response to high- and low-Na diets.
AB  - Previous electrophysiological experiments on renal cortical collecting ducts
      indicated that dietary sodium intake and variations in aldosterone plasma levels
      regulate the abundance of functional epithelial Na channels (ENaC) in the apical
      plasma membrane. In mouse kidney we investigated by immunohistochemistry whether
      feeding for 3 wk a diet with high (3% Na) and low (0.05% Na) Na content
      influences the distribution pattern of ENaC. In mice of all experimental groups,
      ENaC was apparent in cells from the late portion of the distal convoluted tubule
      (DCT2) down to the medullary collecting duct (CD). In mice on a high-Na diet
      (plasma aldosterone: 40.8 +/- 2.0 ng/dl), the alpha-subunit was undetectable, and
      the beta- and gamma-ENaC were detected in the cytoplasm, but not in the apical
      plasma membrane of the cells. In contrast, in mice on a low-Na diet (plasma
      aldosterone: 93.6 +/- 9.3 ng/dl) all three ENaC subunits were displayed in the
      subapical cytoplasm and in the apical membrane of DCT2, connecting tubule (CNT),
      and, although less prominent, in cortical CD cells. Apical plasma membrane
      immunostaining progressively decreased along the cortical CD, simultaneously with
      increasing cytoplasmic staining for beta- and gamma-ENaC. Thus our data on mice
      adapted to moderately low and high Na intake suggest that regulation of ENaC
      function in vivo involves shifts of beta- and gamma-subunits from the cytoplasm
      to the apical plasma membrane and vice versa, respectively. The insertion of
      these subunits into the apical plasma membrane coincides with upregulation of the
      alpha-subunit and its insertion into the apical plasma membrane.

PMID- 10919844
TI  - Influence of nephron mass in development of chronic renal failure after prolonged
      warm renal ischemia.
AB  - The present study examined the long-term consequences of warm renal ischemia
      (WRI) with or without renal ablation. Male Sprague-Dawley rats (250-300 g) were
      subjected to 60 min of complete WRI by pedicle clamping and then followed for 52
      wk. Animals were organized into four groups: rats in which both kidneys were
      subjected to warm ischemia (2WIK); rats with left WRI and right nephrectomy
      (1WIK); uninephrectomized rats with a left nonischemic kidney (1NK); and sham
      operated rats (2NK). Additional animals were studied at 24 h, 7 days, and 16 and
      32 wk. In the first week after WRI, rats from the 2WIK and 1WIK groups displayed
      a similar degree of acute renal damage. After recovering from acute renal
      failure, 1WIK rats developed progressive and severe proteinuria, whereas it was
      mild in the 2WIK group, as well as in the 1NK and 2NK groups. Only animals from
      the 1WIK group developed severe chronic renal failure, glomerulosclerosis,
      interstitial fibrosis, and upregulation of transforming growth factor-beta(1)
      (TGF-beta(1)) gene, which was associated with increased TGF-beta(1) protein
      expression in tubular epithelial cells, arterioles, and in areas of mononuclear
      interstitial cell infiltrate. On the contrary, long-term renal TGF-beta(1)
      expression, function, and histology were similar in 2WIK and 2NK rats. The
      present study shows that prolonged bilateral WRI, when both kidneys are retained
      in place, induces very mild long-term renal lesions as opposed to the severe
      renal scarring observed when WRI is combined with contralateral nephrectomy.

PMID- 10919845
TI  - Shear stress-mediated NO production in inner medullary collecting duct cells.
AB  - Recent evidence suggests that nitric oxide (NO) within the inner medullary
      collecting duct (IMCD) functions to regulate sodium and water reabsorption.
      Because fluid shear stress has been shown to increase NO production in
      endothelial and vascular smooth muscle cells, experiments were designed to
      determine whether a similar mechanism exists in IMCD cells. Cultured IMCD-3 cells
      derived from murine IMCD were subjected to 60 min of pulsatile shear stress.
      Nitrite production (2,3-diaminonaphthalene fluorometric assay) increased 12-, 16
      , and 23-fold at 3.3, 10, and 30 dyn/cm(2), respectively, compared with static
      control cultures. Preincubation with the non-isoform-specific NO synthase
      inhibitor nitro-L-arginine methyl ester reduced nitrite production by 83% in
      response to 30 dyn/cm(2). Western blotting and immunofluorescence analysis of
      static IMCD-3 cell cultures revealed the expression of all three NO synthase
      isoforms (NOS-1 or neuronal NOS, NOS-2 or inducible NOS, and NOS-3 or endothelial
      NOS) in IMCD-3 cultures. These results indicate that NO production is modulated
      by shear stress in IMCD-3 cells and that fluid shear stress within the renal
      tubular system may play a role in the regulation of sodium and water excretion by
      control of NO production in the IMCD.

PMID- 10919846
TI  - Coexpression of neuropilin-1, Flk1, and VEGF(164) in developing and mature mouse
      kidney glomeruli.
AB  - Neuropilin-1, a neuronal cell surface semaphorin III receptor protein important
      for axonal guidance in developing peripheral nervous system efferents, has also
      been identified as a vascular endothelial growth factor (VEGF) receptor on
      endothelial cells. To evaluate its expression in kidney, we carried out RT-PCR on
      newborn and adult total renal RNAs. A 403-bp product, which was predicted to be
      that from neuropilin-1 mRNA, was found in both samples. Nucleotide sequencing
      confirmed that these products encoded neuropilin-1. Northern analysis of newborn
      and adult kidney RNA showed specific hybridization to appropriately sized bands
      of approximately 6 kb. In situ hybridization with a mouse-specific antisense
      neuropilin-1 (35)S-cRNA probe showed distinct glomerular localization on sections
      from both newborns and adults. Similar patterns of hybridization were seen in
      sections treated with antisense cRNA probes against another VEGF receptor, Flk1,
      and with VEGF probes. However, the VEGF hybridization signal was markedly less in
      adult glomeruli than those for neuropilin-1 and Flk1. Because neuropilin-1
      specifically binds VEGF(165) in humans, we carried out RT-PCR on mouse kidney RNA
      with primers that amplified the three alternatively spliced isoforms of VEGF
      mRNA. Our analysis showed that for both newborn and adult kidneys, the relative
      abundance of VEGF mRNA was VEGF(164) >> VEGF(120) > VEGF(188). We conclude that
      the expression of neuropilin-1, in conjunction with Flk1 and VEGF(164), jointly
      contributes to the development and maintenance of glomerular capillaries.

PMID- 10919847
TI  - Regulation of Ca(2+)-activated K(+) channels by multifunctional Ca(2+)/calmodulin
      dependent protein kinase.
AB  - Activation of mesangial cells by ANG II provokes release of intracellular Ca(2+)
      stores and subsequent Ca(2+) influx through voltage-gated channels, events that
      are reflected by a large transient increase in intracellular concentration
      [Ca(2+)](i) followed by a modest sustained elevation in [Ca(2+)](i). These ANG II
      induced alterations in [Ca(2+)](i) elicit activation of large Ca(2+)-activated
      K(+) channels (BK(Ca)) in a negative-feedback manner. The mechanism of this
      BK(Ca) feedback response may involve the direct effect of intracellular Ca(2+) on
      the channel and/or channel activation by regulatory enzymes. The present study
      utilized patch-clamp and fura 2 fluorescence techniques to assess the involvement
      of multifunctional calcium calmodulin kinase II (CAMKII) in the BK(Ca) feedback
      response. In cell-attached patches, KN62 (specific inhibitor of CAMKII) either
      abolished or reduced to near zero the ANG II-induced BK(Ca) feedback response.
      This phenomenon did not reflect direct effects of KN62 on the BK(Ca) channel,
      because this agent alone did not significantly alter BK(Ca) channel activity in
      inside-out patches. KN62 also failed to alter either the transient peak or
      sustained plateau phases of the [Ca(2+)](i) response to ANG II. In inside-out
      patches (1 microM Ca(2+) in bath), calmodulin plus ATP activated BK(Ca) channels
      in the presence but not the absence of CAMKII. These observations are consistent
      with the postulate that CAMKII is involved in the BK(Ca) feedback response of
      mesangial cells, acting to potentiate the influence of increased [Ca(2+)](i) on
      the BK(Ca) channel or a closely associated regulator of the channel. An
      additional effect of CAMKII to activate a voltage-gated Ca(2+) channel cannot be
      ruled out by these experiments.

PMID- 10919848
TI  - Roles of ANG II and bradykinin in the renal regional blood flow responses to ACE
      inhibition in sodium-depleted dogs.
AB  - The relative contributions of ANG II and bradykinin (BK) to the renal regional
      blood flow responses during angiotensin-converting enzyme (ACE) inhibition remain
      unclear. This study was performed to evaluate renal cortical (CBF) and medullary
      blood flow (MBF) responses to intrarterial administration of enalaprilat (33
      microg. kg(-1). min (-1)) after blockade of the ANG II AT(1 )receptors with
      candesartan (100 microg) in 7 dogs fed a low-salt diet (0.01%) for 5 days. Laser
      Doppler flowmetry was used to measure relative changes in CBF and MBF.
      Candesartan alone increased CBF (+20 +/- 2%) and MBF (+22 +/- 7%). Enalaprilat
      infusion after candesartan administration resulted in further increases in both
      CBF (+21 +/- 5%) and MBF (+41 +/- 8%). However, the relative changes in MBF were
      significantly greater (P < 0.01) than those in CBF. Administration of the BK B(2)
      receptor blocker icatibant (300 microg) after enalaprilat returned CBF and MBF to
      values seen with candesartan alone. These data support a substantive role for BK
      potentiation during ACE inhibitor-induced renal vasodilation in dogs maintained
      on a low-sodium diet, with a relatively greater effect on MBF compared to CBF.

PMID- 10919849
TI  - Role of PGE(2) in alpha(2)-induced inhibition of AVP- and cAMP-stimulated H(2)O,
      Na(+), and urea transport in rat IMCD.
AB  - PGE(2) inhibits osmotic water permeability (P(f)) in the rat inner medullary
      collecting duct (IMCD) via cellular events occurring after the stimulation of
      cAMP, i.e., post-cAMP-dependent events. The alpha(2)-agonists also inhibit P(f)
      in the rat IMCD via post-cAMP-dependent events. The purpose of this study was to
      determine whether PGE(2) plays a role in alpha(2)-mediated inhibition of P(f),
      Na(+), and urea transport in the rat IMCD. Isolated terminal IMCDs from Wistar
      rats were perfused to measure, in separate experiments, P(f), lumen-to-bath
      (22)Na(+) transport (J(lb)), and urea permeability (P(u)). Transport was
      stimulated with 220 pM arginine vasopressin (AVP) or 0.1 mM 8-(4
      chlorophenylthio)-cAMP (CPT-cAMP). Indomethacin was used to inhibit endogenous
      prostaglandin synthesis, and the alpha(2)-agonists clonidine, oxymetazoline, and
      dexmedetomidine were used to test the role of PGE(2) in the alpha(2)-mediated
      mechanism that inhibits transport. All agents were added to the bath.
      Indomethacin at 5 microM significantly elevated CPT-cAMP-stimulated P(f), J(lb),
      and P(u), and subsequent addition of 100 nM PGE(2) reduced these transport
      parameters. Indomethacin reversed alpha(2) inhibition of CPT-cAMP-stimulated
      P(f), J(lb), and P(u), and subsequent addition of PGE(2) reduced transport in
      each case. Indomethacin partially reversed alpha(2) inhibition of AVP-stimulated
      P(f), J(lb), and P(u), and PGE(2) reduced transport back to the alpha(2)
      inhibited level. These results indicate that PGE(2) is a second messenger
      involved in the mechanism of transport inhibition mediated by alpha(2)
      adrenoceptors via post-cAMP-dependent events in the rat IMCD.

PMID- 10919850
TI  - TP receptor-mediated vasoconstriction in microperfused afferent arterioles: roles
      of O(2)(-) and NO.
AB  - Thromboxane A(2) (TxA(2)) preferentially constricts the renal afferent arteriole.
      Nitric oxide (NO) modulates vasoconstriction and is rapidly degraded by
      superoxide radical (O(2)(-)). We investigated the roles of NO and O(2)(-) in
      rabbit isolated, perfused renal afferent arteriole responses to the
      TxA(2)/prostaglandin H(2) (TP) receptor agonist U-46,619. U-46,619 (10(-10)-10(
      6) M) dose-dependently reduced afferent arteriolar luminal diameter (ED(50) = 7.5
      +/- 5.0 nM), which was blocked by the TP receptor antagonist ifetroban (10(-6)
      M). Tempol (10(-3) M) pretreatment, which prevented paraquat-induced
      vasoconstriction in afferent arterioles, blocked the vasoconstrictor responses to
      U-46,619. To test whether U-46,619 stimulates NO and whether tempol prevents U
      46, 619-induced vasoconstriction by enhancing the biological activity of NO, we
      examined the luminal diameter response to U-46,619 in arterioles pretreated with
      N(w)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) or L-NAME + tempol. During
      L-NAME, the sensitivity and maximal responses of the afferent arteriole to U-46,
      619 were significantly (P < 0.05) enhanced. Moreover, L-NAME restored a
      vasoconstrictor response to U-46,619 in vessels pretreated with tempol. In
      conclusion, in isolated perfused renal afferent arterioles TP receptor activation
      stimulates NO production, which buffers the vasoconstriction, and stimulates
      O(2)(-) production, which mediates the vasoconstriction, in part, through
      interaction with NO.

PMID- 10919851
TI  - Selective estrogen receptor modulators suppress mesangial cell collagen
      synthesis.
AB  - Estrogen receptor modulators (SERMs) are "designer drugs" that exert estrogen
      like actions in some cells but not in others. We examined the effects of the
      SERMs LY-117018 (an analog of raloxifene) and tamoxifen on mesangial cells
      synthesis of type I and type IV collagen. We found that LY-117018 and tamoxifen
      suppressed mesangial cell type IV collagen gene transcription and type IV
      collagen protein synthesis in a dose-dependent manner, with a potency identical
      to that of estradiol. Type I collagen synthesis was also suppressed by LY-117018
      in a dose-dependent manner with a potency identical to that of estradiol but
      greater than that of tamoxifen. Genistein, which selectively binds to estrogen
      receptor-beta in nanomolar concentrations, suppressed type I and type IV collagen
      synthesis, suggesting that estrogen receptor-beta mediates the effects of
      estrogen on collagen synthesis. Because matrix accumulation is central to the
      development of glomerulosclerosis, second-generation SERMs may prove clinically
      useful in ameliorating progressive renal disease without the adverse effects of
      estrogen on reproductive tissues.

PMID- 10919852
TI  - Impairment of pressure-natriuresis and renal autoregulation in ANG II-infused
      hypertensive rats.
AB  - Chronic infusions of initially subpressor doses of angiotensin II (ANG II) lead
      to progressive hypertension over a 2-wk period and to augmented intrarenal ANG II
      levels. The present study was performed to investigate total renal blood flow
      (RBF) and medullary blood flow (MBF) autoregulatory behavior and pressure
      natriuresis in ANG II-infused hypertensive rats and how these are modified by
      concomitant treatment with an ANG II AT(1) receptor antagonist. ANG II-infused
      rats (n = 27) were prepared by administration of ANG II at 60 ng/min via osmotic
      minipump for 13 days. Twelve of the ANG II-infused hypertensive rats were treated
      with losartan in the drinking water (30 mg. kg.(-1) day(-1)). Rats were
      anesthetized with pentobarbital sodium (50 mg/kg, ip) and prepared for renal
      function measurements. An aortic clamp was placed above the junction of the left
      renal artery to reduce renal arterial pressure. Autoregulatory responses for
      renal plasma flow, overall RBF, and glomerular filtration rate were impaired in
      ANG II-infused hypertensive rats; however, MBF autoregulation was not disrupted.
      Most strikingly, pressure-natriuresis was markedly suppressed in ANG II-infused
      hypertensive rats. Chronic treatment with losartan prevented the impairment of
      the pressure-natriuresis relationship caused by chronic ANG II infusion. These
      findings demonstrate that chronic ANG II infusion leads to marked impairment of
      sodium excretion and suppression of the pressure-natriuresis relationship, which
      may contribute to the progressive hypertension that occurs in this model. These
      renal effects are prevented by simultaneous treatment with an AT(1) receptor
      blocker.

PMID- 10919854
TI  - Modeling exchange of plasma proteins between microcirculation and interstitium of
      the renal medulla.
AB  - In the absence of evidence for lymphatics in the inner medulla of the kidney, it
      has been proposed that plasma proteins are cleared by convection out of the
      medullary interstitial fluid (ISF) directly into the ascending vasa recta (AVR).
      To clarify this hypothesis we have developed a mathematical model of the
      microvascular exchange of fluid, plasma proteins, and small solutes among the
      descending vasa recta (DVR), the AVR, and the ISF. The model represents the DVR
      and AVR as limbs of a countercurrent exchange loop separated and surrounded by
      the ISF. Steady-state exchange of fluid and solute are considered by using
      conservation and exchange equations. We have used values for parameters based on
      experimental measurements and investigated the effects of the properties of the
      vasa recta, the flow, and the gradient of small solutes on the distribution of
      plasma proteins. Results from the model agree reasonably well with experimental
      measurements, suggesting that convection may account for the clearance of plasma
      proteins from the renal medulla maintaining their concentration below that of the
      AVR.

PMID- 10919853
TI  - Endothelin inhibits thick ascending limb chloride flux via ET(B) receptor
      mediated NO release.
AB  - Endothelin-1 (ET-1) inhibits transport in various nephron segments, and the thick
      ascending limb of the loop of Henle (TALH) expresses ET-1 receptors. In many
      tissues, activation of ET(B) receptors stimulates release of NO, and we recently
      reported that endogenous NO inhibits TALH chloride flux (J(Cl)). However, the
      relationship between ET-1 and NO in the control of nephron transport has not been
      extensively studied. We hypothesized that ET-1 decreases NaCl transport by
      cortical TALHs through activation of ET(B) receptors and release of NO. Exogenous
      ET-1 (1 nM) decreased J(Cl) from 118.3 +/- 15.0 to 62.7 +/- 13.6 pmol. mm(-1).
      min(-1) (48.3 +/- 8.2% reduction), whereas removal of ET-1 increased J(Cl) in a
      separate group of tubules from 87.6 +/- 10.7 to 115.2 +/- 10.3 pmol. mm(-1). min(
      1) (34.5 +/- 6.2% increase). To determine whether NO mediates the inhibitory
      effects of ET-1 on J(Cl), we examined the effect of inhibiting of NO synthase
      (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME) on ET-1-induced changes in
      J(Cl). L-NAME (5 mM) completely prevented the ET-1-induced reduction in J(Cl),
      whereas D-NAME did not. L-NAME alone had no effect on J(Cl). These data suggest
      that the effects of ET-1 are mediated by NO. Blockade of ET(B) receptors with BQ
      788 prevented the inhibitory effects of 1 nM ET-1. Activation of ET(B) receptors
      with sarafotoxin S6c mimicked the inhibitory effect of ET-1 on J(Cl) (from 120.7
      +/- 12.6 to 75.4 +/- 13.3 pmol. mm(-1). min(-1)). In contrast, ET(A) receptor
      antagonism with BQ-610 did not prevent ET-1-mediated inhibition of TALH J(Cl)
      (from 96.5 +/- 10.4 to 69.5 +/- 8.6 pmol. mm(-1). min(-1)). Endothelin increased
      intracellular calcium from 96.9 +/- 14.0 to 191.4 +/- 11.9 nM, an increase of
      110.8 +/- 26.1%. We conclude that exogenous endothelin indirectly decreases TALH
      J(Cl) by activating ET(B) receptors, increasing intracellular calcium
      concentration, and stimulating NO release. These data suggest that endothelin
      acts as a physiological regulator of TALH NO synthesis, thus inhibiting chloride
      transport and contributing to the natriuretic effects of ET-1 observed in vivo.

PMID- 10919855
TI  - Urea protects from the proapoptotic effect of NaCl in renal medullary cells.
AB  - Hypertonic NaCl upregulated two sensitive and specific biochemical indices of
      apoptosis, caspase-3 activation and annexin V binding, in a time- and dose
      dependent fashion in renal medullary mIMCD3 cells. Pretreatment with urea (200 mM
      for 30 min) protected from the proapoptotic effect of hypertonic stress (200
      mosmol/kgH(2)O) in this model. The protective effect of urea was dose dependent
      and was effective even when applied a short time (< or =1 h) following NaCl
      exposure; this protective effect was not observed in the nonrenal 3T3 cell line.
      In both mIMCD3 and 3T3 cells, urea failed to protect from the proapoptotic
      stressor, ultraviolet (UV)-B irradiation. The ability of urea to protect from
      hypertonic stress was approximately comparable to the protective effect of
      peptide mitogens epidermal growth factor and insulin-like growth factor (IGF),
      but it potentiated the IGF effect. Interestingly, the tyrosine kinase inhibitor,
      genistein, potentiated the proapoptotic effect of urea yet abrogated the
      proapoptotic effect of hypertonic stress. In aggregate, these data indicate that
      urea protects from the proapoptotic effect of hypertonic stress in a potentially
      cell type-specific and stimulus-specific fashion.

PMID- 10919856
TI  - Renal interstitial hydrostatic pressure and pressure natriuresis in pregnant
      rats.
AB  - The objective of this study was to test the hypothesis that a decrease in renal
      interstitial hydrostatic pressure (RIHP) accounts for the blunted pressure
      natriuresis during pregnancy. RIHP was measured in nonpregnant (NP; n = 9),
      midterm pregnant (MP; 12-14 days after conception; n = 10), and late-term
      pregnant (LP; 18-21 days after conception; n = 12) female Sprague-Dawley rats at
      two renal perfusion pressure (RPP) levels (99 and 120 mmHg). At the lower RPP
      level, RIHP was 5.9 +/- 0.3 mmHg for NP, 3.4 +/- 0.4 mmHg for MP (P < 0.05 vs.
      NP), and 2.9 +/- 0.1 mmHg for LP (P < 0.05 vs. NP) rats. The increase in RPP from
      99 to 120 mmHg resulted in pressure natriuretic and diuretic responses in all
      groups; however, the increases in fractional excretion of sodium (DeltaFE(Na)),
      urine flow rate (DeltaV), and DeltaRIHP were significantly greater (P < 0. 05) in
      NP compared with both MP and LP rats. DeltaFE(Na), DeltaV, and DeltaRIHP were
      2.06 +/- 0.28%, 81.44 +/- 14.10 microl/min, and 3. 0 +/- 0.5 mmHg for NP; 0.67 +/
      0.13%, 28.03 +/- 5.28 microl/min, and 0.5 +/- 0.2 mmHg for MP; and 0.48 +/-
      0.12%, 18.14 +/- 4.70 microl/min, and 0.4 +/- 0.1 mmHg for LP rats. In
      conclusion, RIHP is significantly lower in pregnant compared with nonpregnant
      rats at similar RPP levels. Also, the ability of pregnant rats to increase RIHP
      in response to an increase in RPP is blunted. These changes in RIHP may play an
      important role in the blunted pressure natriuresis and contribute to the
      conservation of sodium and water that is critical for fetal growth and
      development during normal pregnancy.

PMID- 10919857
TI  - Proximal tubule Na transporter responses are the same during acute and chronic
      hypertension.
AB  - Acute hypertension in Sprague-Dawley rats (SD) provokes a decrease in renal
      proximal tubule (PT) salt and fluid reabsorption, redistribution of apical Na/H
      exchanger isoform 3 (NHE3) and Na-P(i) cotransporter type 2 (NaPi2) out of the
      brush border into higher density membranes, and inhibition of renal cortical Na-K
      ATPase (NKA) activity (41). The aims of this study were to determine 1) whether
      an increase in arterial pressure affects distribution or activity of Na
      transporters in the spontaneously hypertensive rat (SHR) and 2) whether
      development of chronic hypertension in SHR leads to persistent adaptive changes
      in NHE3 and NaPi2 distribution and/or NKA activity. Renal cortex Na transporter
      protein density distributions and activities were compared by subcellular
      fractionation in 1) adult SHR with an acute increase or decrease in arterial
      pressure and 2) young SD (YSD) and young SHR (YSHR) vs. adult SD and SHR. In
      adult hypertensive SHR NHE3 was shifted to membranes of higher densities,
      analogous to SD with acute hypertension, and there were no further changes with a
      further increase or decrease in arterial pressure. There was no change in total
      pool size of NHE3 in cortex in YSHR vs. SHR. NHE3, NaPi2, megalin, NKA alpha
      /beta-subunit, dipeptidyl peptidase IV (DPPIV), and villin distributions were the
      same in YSHR vs. YSD. NHE3, NaPi2, and megalin shifted to higher densities in
      adult SHR, but not SD, with age. Basolateral NKA and apical alkaline phosphatase
      activities were 40% greater in YSHR than YSD and decreased to SD levels in
      adults. We conclude that there are persistent changes in Na(+) transporter
      distributions and activity in response to chronic hypertension in SHR that mimic
      the responses to acute hypertension seen in SD rats and that elevated sodium pump
      activity per transporter in YSHR may contribute to the generation of
      hypertension.

PMID- 10919858
TI  - Vasopressin V(2)-receptor-dependent regulation of AQP2 expression in Brattleboro
      rats.
AB  - The role of AVP-V(2) receptor (AVP-V(2)R)-dependent regulation of aquaporin-2
      (AQP2) expression was evaluated in vasopressin-deficient Brattleboro (BB) rats.
      AQP2 levels were relatively high in BB rats (52 +/- 8% of levels in Wistar rats),
      and treatment with the AVP-V(2)R antagonist SR-121463A (0.8 mg/day) for 48 h was
      associated with 1) increased urine output (170 +/- 9%), 2), reduced AQP2 protein
      levels (42 +/- 10% in whole kidney and 53 +/- 8% in inner medulla), and 3)
      reduced AQP2 mRNA levels (36 +/- 7%). In addition, the levels of AQP2
      phosphorylated in the protein kinase A (PKA) consensus site (Ser(256) of AQP2)
      was reduced to 3 +/- 1% of control levels. Lithium (Li) treatment of BB rats for
      1 mo, known to reduce adenylyl cyclase (AC) activity, downregulated AQP2 protein
      levels (15 +/- 6%) and increased urine output (220%). Downregulation of AQP2
      expression in response to SR-121463A or Li treatment indicates that AQP2
      expression in BB rats depends in part on activation of AVP-V(2)Rs and that the
      signaling cascade(s) involves AC and hence cAMP. Complete water restriction of BB
      rats produced only a small increase in AQP2 mRNA (235 +/- 33%) and AQP2 protein
      (156 +/- 22%) levels. Immunoelectron microscopy confirmed the increase in AQP2
      abundance but revealed no change in AQP2 apical plasma membrane labeling in
      response to thirsting. In conclusion, the expression and phosphorylation of AQP2
      in BB rats are in part dependent on AVP-V(2)R signaling, and AVP-V(2)-mediated
      regulation of AQP2 trafficking and expression is effectively decoupled in BB
      rats, indicating differences in AVP-V(2)R-mediated regulation of AQP2 trafficking
      and expression.

PMID- 10919859
TI  - Use of serial analysis of gene expression to generate kidney expression
      libraries.
AB  - Chronic renal disease initiation and progression remain incompletely understood.
      Genome-wide expression monitoring should clarify mechanisms that cause
      progressive renal disease by determining how clusters of genes coordinately
      change their activity. Serial analysis of gene expression (SAGE) is a technique
      of expression profiling, which permits simultaneous, comparative, and
      quantitative analysis of gene-specific, 9- to 13-bp sequence tags. Using SAGE, we
      have constructed a tag expression library from ROP-+/+ mouse kidney. Tag
      sequences were sorted by abundance, and identity was determined by sequence
      homology searching. Analyses of 3,868 tags yielded 1,453 unique kidney
      transcripts. Forty-two percent of these transcripts matched mRNA sequence entries
      with known function, 35% of the transcripts corresponded to expressed sequence
      tag (EST) entries or cloned genes, whose function has not been established, and
      23% represented unidentified genes. Previously characterized transcripts were
      clustered into functional groups, and those encoding metabolic enzymes, plasma
      membrane proteins (transporters/receptors), and ribosomal proteins were most
      abundant (39, 14, and 12% of known transcripts, respectively). The most common,
      kidney-specific transcripts were kidney androgen-regulated protein (4% of all
      transcripts), sodium-phosphate cotransporter (0.3%), renal cytochrome P-450
      (0.3%), parathyroid hormone receptor (0.1%), and kidney-specific cadherin (0.1%).
      Comprehensively characterizing and contrasting gene expression patterns in normal
      and diseased kidneys will provide an alternative strategy to identify candidate
      pathways, which regulate nephropathy susceptibility and progression, and novel
      targets for therapeutic intervention.

PMID- 10919860
TI  - A mathematical model of solute coupled water transport in toad intestine
      incorporating recirculation of the actively transported solute.
AB  - A mathematical model of an absorbing leaky epithelium is developed for analysis
      of solute coupled water transport. The non-charged driving solute diffuses into
      cells and is pumped from cells into the lateral intercellular space (lis). All
      membranes contain water channels with the solute passing those of tight junction
      and interspace basement membrane by convection-diffusion. With solute
      permeability of paracellular pathway large relative to paracellular water flow,
      the paracellular flux ratio of the solute (influx/outflux) is small (2-4) in
      agreement with experiments. The virtual solute concentration of fluid emerging
      from lis is then significantly larger than the concentration in lis. Thus, in
      absence of external driving forces the model generates isotonic transport
      provided a component of the solute flux emerging downstream lis is taken up by
      cells through the serosal membrane and pumped back into lis, i.e., the solute
      would have to be recirculated. With input variables from toad intestine
      (Nedergaard, S., E.H. Larsen, and H.H. Ussing, J. Membr. Biol. 168:241-251),
      computations predict that 60-80% of the pumped flux stems from serosal bath in
      agreement with the experimental estimate of the recirculation flux. Robust
      solutions are obtained with realistic concentrations and pressures of lis, and
      with the following features. Rate of fluid absorption is governed by the solute
      permeability of mucosal membrane. Maximum fluid flow is governed by density of
      pumps on lis-membranes. Energetic efficiency increases with hydraulic conductance
      of the pathway carrying water from mucosal solution into lis. Uphill water
      transport is accomplished, but with high hydraulic conductance of cell membranes
      strength of transport is obscured by water flow through cells. Anomalous solvent
      drag occurs when back flux of water through cells exceeds inward water flux
      between cells. Molecules moving along the paracellular pathway are driven by a
      translateral flow of water, i.e., the model generates pseudo-solvent drag. The
      associated flux-ratio equation is derived.

PMID- 10919862
TI  - Transfected cyclic nucleotide-gated channels as biosensors.

PMID- 10919861
TI  - A Cl(-) cotransporter selective for NH(4)(+) over K(+) in glial cells of bee
      retina.
AB  - There appears to be a flux of ammonium (NH(4)(+)/NH(3)) from neurons to glial
      cells in most nervous tissues. In bee retinal glial cells, NH(4)(+)/NH(3) uptake
      is at least partly by chloride-dependant transport of the ionic form NH(4)(+).
      Transmembrane transport of NH(4)(+) has been described previously on transporters
      on which NH(4)(+) replaces K(+), or, more rarely, Na(+) or H(+), but no transport
      system in animal cells has been shown to be selective for NH(4)(+) over these
      other ions. To see if the NH(4)(+)-Cl(-) cotransporter on bee retinal glial cells
      is selective for NH(4)(+) over K(+) we measured ammonium-induced changes in
      intracellular pH (pH(i)) in isolated bundles of glial cells using a fluorescent
      indicator. These changes in pH(i) result from transmembrane fluxes not only of
      NH(4)(+), but also of NH(3). To estimate transmembrane fluxes of NH(4)(+), it was
      necessary to measure several parameters. Intracellular pH buffering power was
      found to be 12 mM. Regulatory mechanisms tended to restore intracellular [H(+)]
      after its displacement with a time constant of 3 min. Membrane permeability to
      NH(3) was 13 microm s(-1). A numerical model was used to deduce the NH(4)(+) flux
      through the transporter that would account for the pH(i) changes induced by a 30
      s application of ammonium. This flux saturated with increasing [NH(4)(+)](o); the
      relation was fitted with a Michaelis-Menten equation with K(m) approximately 7
      mM. The inhibition of NH(4)(+) flux by extracellular K(+) appeared to be
      competitive, with an apparent K(i) of approximately 15 mM. A simple standard
      model of the transport process satisfactorily described the pH(i) changes caused
      by various experimental manipulations when the transporter bound NH(4)(+) with
      greater affinity than K(+). We conclude that this transporter is functionally
      selective for NH(4)(+) over K(+) and that the transporter molecule probably has a
      greater affinity for NH(4)(+) than for K(+).

PMID- 10919864
TI  - Severed molecules functionally define the boundaries of the cystic fibrosis
      transmembrane conductance regulator's NH(2)-terminal nucleotide binding domain.
AB  - The cystic fibrosis transmembrane conductance regulator is a Cl(-) channel that
      belongs to the family of ATP-binding cassette proteins. The CFTR polypeptide
      comprises two transmembrane domains, two nucleotide binding domains (NBD1 and
      NBD2), and a regulatory (R) domain. Gating of the channel is controlled by kinase
      mediated phosphorylation of the R domain and by ATP binding, and, likely,
      hydrolysis at the NBDs. Exon 13 of the CFTR gene encodes amino acids (aa's) 590
      830, which were originally ascribed to the R domain. In this study, CFTR channels
      were severed near likely NH(2)- or COOH-terminal boundaries of NBD1. CFTR channel
      activity, assayed using two-microelectrode voltage clamp and excised patch
      recordings, provided a sensitive measure of successful assembly of each pair of
      channel segments as the sever point was systematically shifted along the primary
      sequence. Substantial channel activity was taken as an indication that NBD1 was
      functionally intact. This approach revealed that the COOH terminus of NBD1
      extends beyond aa 590 and lies between aa's 622 and 634, while the NH(2) terminus
      of NBD1 lies between aa's 432 and 449. To facilitate biochemical studies of the
      expressed proteins, a Flag epitope was added to the NH(2) termini of full length
      CFTR, and of CFTR segments truncated before the normal COOH terminus (aa 1480).
      The functionally identified NBD1 boundaries are supported by Western blotting,
      coimmunoprecipitation, and deglycosylation studies, which showed that an NH(2)
      terminal segment representing aa's 3-622 (Flag3-622) or 3-633 (Flag3-633) could
      physically associate with a COOH-terminal fragment representing aa's 634-1480
      (634-1480); however, the latter fragment was glycosylated to the mature form only
      in the presence of Flag3-633. Similarly, 433-1480 could physically associate with
      Flag3-432 and was glycosylated to the mature form; however, 449-1480 protein
      seemed unstable and could hardly be detected even when expressed with Flag3-432.
      In excised-patch recordings, all functional severed CFTR channels displayed the
      hallmark characteristics of CFTR, including the requirement of phosphorylation
      and exposure to MgATP for gating, ability to be locked open by pyrophosphate or
      AMP-PNP, small single channel conductances, and high apparent affinity of channel
      opening by MgATP. Our definitions of the boundaries of the NBD1 domain in CFTR
      are supported by comparison with the solved NBD structures of HisP and RbsA.

PMID- 10919863
TI  - Cyclic nucleotide-gated channels colocalize with adenylyl cyclase in regions of
      restricted cAMP diffusion.
AB  - Cyclic AMP is a ubiquitous second messenger that coordinates diverse cellular
      functions. Current methods for measuring cAMP lack both temporal and spatial
      resolution, leading to the pervasive notion that, unlike Ca(2+), cAMP signals are
      simple and contain little information. Here we show the development of adenovirus
      expressed cyclic nucleotide-gated channels as sensors for cAMP. Homomultimeric
      channels composed of the olfactory alpha subunit responded rapidly to jumps in
      cAMP concentration, and their cAMP sensitivity was measured to calibrate the
      sensor for intracellular measurements. We used these channels to detect cAMP,
      produced by either heterologously expressed or endogenous adenylyl cyclase, in
      both single cells and cell populations. After forskolin stimulation, the
      endogenous adenylyl cyclase in C6-2B glioma cells produced high concentrations of
      cAMP near the channels, yet the global cAMP concentration remained low. We found
      that rapid exchange of the bulk cytoplasm in whole-cell patch clamp experiments
      did not prevent the buildup of significant levels of cAMP near the channels in
      human embryonic kidney 293 (HEK-293) cells expressing an exogenous adenylyl
      cyclase. These results can be explained quantitatively by a cell compartment
      model in which cyclic nucleotide-gated channels colocalize with adenylyl cyclase
      in microdomains, and diffusion of cAMP between these domains and the bulk cytosol
      is significantly hindered. In agreement with the model, we measured a slow rate
      of cAMP diffusion from the whole-cell patch pipette to the channels (90% exchange
      in 194 s, compared with 22-56 s for substances that monitor exchange with the
      cytosol). Without a microdomain and restricted diffusional access to the cytosol,
      we are unable to account for all of the results. It is worth noting that in
      models of unrestricted diffusion, even in extreme proximity to adenylyl cyclase,
      cAMP does not reach high enough concentrations to substantially activate PKA or
      cyclic nucleotide-gated channels, unless the entire cell fills with cAMP. Thus,
      the microdomains should facilitate rapid and efficient activation of both PKA and
      cyclic nucleotide-gated channels, and allow for local feedback control of
      adenylyl cyclase. Localized cAMP signals should also facilitate the differential
      regulation of cellular targets.

PMID- 10919865
TI  - Collapse of conductance is prevented by a glutamate residue conserved in voltage
      dependent K(+) channels.
AB  - Voltage-dependent K(+) channel gating is influenced by the permeating ions.
      Extracellular K(+) determines the occupation of sites in the channels where the
      cation interferes with the motion of the gates. When external [K(+)] decreases,
      some K(+) channels open too briefly to allow the conduction of measurable
      current. Given that extracellular K(+) is normally low, we have studied if
      negatively charged amino acids in the extracellular loops of Shaker K(+) channels
      contribute to increase the local [K(+)]. Surprisingly, neutralization of the
      charge of most acidic residues has minor effects on gating. However, a glutamate
      residue (E418) located at the external end of the membrane spanning segment S5 is
      absolutely required for keeping channels active at the normal external [K(+)].
      E418 is conserved in all families of voltage-dependent K(+) channels. Although
      the channel mutant E418Q has kinetic properties resembling those produced by
      removal of K(+) from the pore, it seems that E418 is not simply concentrating
      cations near the channel mouth, but has a direct and critical role in gating. Our
      data suggest that E418 contributes to stabilize the S4 voltage sensor in the
      depolarized position, thus permitting maintenance of the channel open
      conformation.

PMID- 10919866
TI  - Conjoint control of hippocampal place cell firing by two visual stimuli. I. The
      effects of moving the stimuli on firing field positions.
AB  - To better understand how hippocampal place cell activity is controlled by sensory
      stimuli, and to further elucidate the nature of the environmental representation
      provided by place cells, we have made recordings in the presence of two distinct
      visual stimuli under standard conditions and after several manipulations of these
      stimuli. In line with a great deal of earlier work, we find that place cell
      activity is constant when repeated recordings are made in the standard conditions
      in which the centers of the two stimuli, a black card and a white card, are
      separated by 135 degrees on the wall of a cylindrical recording chamber. Rotating
      the two stimuli by 45 degrees causes equal rotations of place cell firing fields.
      Removing either card and rotating the other card also causes fields to rotate
      equally, showing that the two stimuli are individually salient. Increasing or
      decreasing the card separation (card reconfiguration) causes a topological
      distortion of the representation of the cylinder floor such that field centers
      move relative to each other. We also found that either kind of reconfiguration
      induces a position-independent decrease in the intensity of place cell firing. We
      argue that these results are not compatible with either of two previously stated
      views of the place cell representation; namely, a nonspatial theory in which each
      place cell is tuned to an arbitrarily selected subset of available stimuli or a
      rigid map theory. We propose that our results imply that the representation is
      map-like but not rigid; it is capable of undergoing stretches without altering
      the local arrangement of firing fields.

PMID- 10919867
TI  - Conjoint control of hippocampal place cell firing by two visual stimuli. Ii. A
      vector-field theory that predicts modifications of the representation of the
      environment.
AB  - Changing the angular separation between two visual stimuli attached to the wall
      of a recording cylinder causes the firing fields of place cells to move relative
      to each other, as though the representation of the floor undergoes a topological
      distortion. The displacement of the firing field center of each cell is a vector
      whose length is equal to the linear displacement and whose angle indicates the
      direction that the field center moves in the environment. Based on the
      observation that neighboring fields move in similar ways, whereas widely
      separated fields tend to move relative to each other, we develop an empirical
      vector-field model that accounts for the stated effects of changing the card
      separation. We then go on to show that the same vector-field equation predicts
      additional aspects of the experimental results. In one example, we demonstrate
      that place cell firing fields undergo distortions of shape after the card
      separation is changed, as though different parts of the same field are affected
      by the stimulus constellation in the same fashion as fields at different
      locations. We conclude that the vector-field formalism reflects the organization
      of the place-cell representation of the environment for the current case, and
      through suitable modification may be very useful for describing motions of firing
      patterns induced by a wide variety of stimulus manipulations.

PMID- 10919868
TI  - "Light" reading: targeting tryptophans in cyclic nucleotide-gated channels.

PMID- 10919870
TI  - Effects of ultraviolet modification on the gating energetics of cyclic nucleotide
      gated channels.
AB  - Middendorf et al. (Middendorf, T.R., R.W. Aldrich, and D.A. Baylor. 2000. J. Gen.
      Physiol. 116:227-252) showed that ultraviolet light decreases the current through
      cloned cyclic nucleotide-gated channels from bovine retina activated by high
      concentrations of cGMP. Here we probe the mechanism of the current reduction. The
      channels' open probability before irradiation, P(o)(0), determined the sign of
      the change in current amplitude that occurred upon irradiation. UV always
      decreased the current through channels with high initial open probabilities
      [P(o)(0) > 0.3]. Manipulations that promoted channel opening antagonized the
      current reduction by UV. In contrast, UV always increased the current through
      channels with low initial open probabilities [P(o)(0) < or = 0.02], and the
      magnitude of the current increase varied inversely with P(o)(0). The dual effects
      of UV on channel currents and the correlation of both effects with P(o)(0)
      suggest that the channels contain two distinct classes of UV target residues
      whose photochemical modification exerts opposing effects on channel gating. We
      present a simple model based on this idea that accounts quantitatively for the UV
      effects on the currents and provides estimates for the photochemical quantum
      yields and free energy costs of modifying the UV targets. Simulations indicate
      that UV modification may be used to produce and quantify large changes in channel
      gating energetics in regimes where the associated changes in open probability are
      not measurable by existing techniques.

PMID- 10919869
TI  - Modification of cyclic nucleotide-gated ion channels by ultraviolet light.
AB  - We irradiated cyclic nucleotide-gated ion channels in situ with ultraviolet light
      to probe the role of aromatic residues in ion channel function. UV light reduced
      the current through excised membrane patches from Xenopus oocytes expressing the
      alpha subunit of bovine retinal cyclic nucleotide-gated channels irreversibly, a
      result consistent with permanent covalent modification of channel amino acids by
      UV light. The magnitude of the current reduction depended only on the total
      photon dose delivered to the patches, and not on the intensity of the exciting
      light, indicating that the functionally important photochemical modification(s)
      occurred from an excited state reached by a one-photon absorption process. The
      wavelength dependence of the channels' UV light sensitivity (the action spectrum)
      was quantitatively consistent with the absorption spectrum of tryptophan, with a
      small component at long wavelengths, possibly due to cystine absorption. This
      spectral analysis suggests that UV light reduced the currents at most wavelengths
      studied by modifying one or more "target" tryptophans in the channels. Comparison
      of the channels' action spectrum to the absorption spectrum of tryptophan in
      various solvents suggests that the UV light targets are in a water-like chemical
      environment. Experiments on mutant channels indicated that the UV light
      sensitivity of wild-type channels was not conferred exclusively by any one of the
      10 tryptophan residues in a subunit. The similarity in the dose dependences of
      channel current reduction and tryptophan photolysis in solution suggests that
      photochemical modification of a small number of tryptophan targets in the
      channels is sufficient to decrease the currents.

PMID- 10919871
TI  - Effect of 11-cis 13-demethylretinal on phototransduction in bleach-adapted rod
      and cone photoreceptors.
AB  - We used 11-cis 13-demethylretinal to examine the physiological consequences of
      retinal's noncovalent interaction with opsin in intact rod and cone
      photoreceptors during visual pigment regeneration. 11-Cis 13-demethylretinal is
      an analog of 11-cis retinal in which the 13 position methyl group has been
      removed. Biochemical experiments have shown that it is capable of binding in the
      chromophore pocket of opsin, forming a Schiff-base linkage with the protein to
      produce a pigment, but at a much slower rate than the native 11-cis retinal
      (Nelson, R., J. Kim deReil, and A. Kropf. 1970. Proc. Nat. Acad. Sci. USA. 66:531
      538). Experimentally, this slow rate of pigment formation should allow separate
      physiological examination of the effects of the initial binding of retinal in the
      pocket and the subsequent formation of the protonated Schiff-base linkage.
      Currents from solitary rods and cones from the tiger salamander were recorded in
      darkness before and after bleaching and then after exposure to 11-cis 13
      demethylretinal. In bleach-adapted rods, 11-cis 13-demethylretinal caused
      transient activation of phototransduction, as evidenced by a decrease of the dark
      current and sensitivity, acceleration of the dim flash responses, and activation
      of cGMP phosphodiesterase and guanylyl cyclase. The steady state of
      phototransduction activity was still higher than that of the bleach-adapted rod.
      In contrast, exposure of bleach-adapted cones to 11-cis 13-demethylretinal
      resulted in an immediate deactivation of transduction as measured by the same
      parameters. These results extend the validity of a model for the effects of the
      noncovalent binding of a retinoid in the chromophore pockets of rod and cone
      opsins to analogs capable of forming a Schiff-base and imply that the noncovalent
      binding by itself may play a role for the dark adaptation of photoreceptors.

PMID- 10919875
TI  - Author's reply

PMID- 10919873
TI  - Effect of feeding level and thyroxine on adipose tissue development and growth in
      postnatal lambs.
AB  - We investigated the influence of exogenous thyroxine (T4) administration in
      conjunction with level of feeding on adipose tissue and liver growth in postnatal
      lambs. Pairs of lambs were fed either 100 g (i.e. low fed) or 200 g (i.e. high
      fed) of milk powder per litre of reconstituted milk replacer over the first month
      of life. Half of the pairs of lambs were fed a bolus dose of T4 (15 mg (kg body
      weight)-1) daily until 8 days of age. Perirenal adipose tissue and hepatic tissue
      were sampled at either 8 or 35 days of age. High fed lambs grew faster, possessed
      more adipose tissue and had larger livers than low fed lambs at 8 and 35 days of
      age. T4 administration resulted in a lower thermogenic activity (i.e. GDP
      binding) in adipose tissue at 8 days of age in low, but not high fed lambs. There
      was no difference between groups in colonic temperature or oxygen consumption.
      Between 17 and 35 days of age high fed lambs previously treated with T4 had lower
      daily milk consumption than untreated siblings, but still attained the same
      growth rate. Plasma insulin-like growth factor-I concentrations were greater in
      high than low fed lambs, a relationship that was not influenced by T4 treatment.
      In adipose tissue, iodothyronine 5' deiodinase activity was not influenced by T4
      administration and was greater in high than low fed lambs. Hepatic iodothyronine
      5' deiodinase activity was not influenced by T4 administration in low fed lambs,
      but was reduced by T4 in high fed lambs. In conclusion, T4 administration over
      the first 8 days of life can accelerate the rate of decline in thermogenic
      activity of uncoupling protein-1. This effect is not observed when the level of
      feeding is increased. Following withdrawal of T4 treatment, high fed T4-treated
      lambs were able to maintain the same growth rate as untreated lambs despite
      having a lower food intake.

PMID- 10919872
TI  - Extracellular ATP inhibits the small-conductance K channel on the apical membrane
      of the cortical collecting duct from mouse kidney.
AB  - We have used the patch-clamp technique to study the effects of changing
      extracellular ATP concentration on the activity of the small-conductance
      potassium channel (SK) on the apical membrane of the mouse cortical collecting
      duct. In cell-attached patches, the channel conductance and kinetics were similar
      to its rat homologue. Addition of ATP to the bathing solution of split-open
      single cortical collecting ducts inhibited SK activity. The inhibition of the
      channel by ATP was reversible, concentration dependent (K(i) = 64 microM), and
      could be completely prevented by pretreatment with suramin, a specific purinergic
      receptor (P(2)) blocker. Ranking of the inhibitory potency of several nucleotides
      showed strong inhibition by ATP, UTP, and ATP-gamma-S, whereas alpha, beta-Me
      ATP, and 2-Mes ATP failed to affect channel activity. This nucleotide sensitivity
      is consistent with P(2)Y(2) purinergic receptors mediating the inhibition of SK
      by ATP. Single channel analysis further demonstrated that the inhibitory effects
      of ATP could be elicited through activation of apical receptors. Moreover, the
      observation that fluoride mimicked the inhibitory action of ATP suggests the
      activation of G proteins during purinergic receptor stimulation. Channel
      inhibition by ATP was not affected by blocking phospholipase C and protein kinase
      C. However, whereas cAMP prevented channel blocking by ATP, blocking protein
      kinase A failed to abolish the inhibitory effects of ATP. The reduction of K
      channel activity by ATP could be prevented by okadaic acid, an inhibitor of
      protein phosphatases, and KT5823, an agent that blocks protein kinase G.
      Moreover, the effect of ATP was mimicked by cGMP and blocked by L-NAME (N(G)
      nitro-l-arginine methyl ester). We conclude that the inhibitory effect of ATP on
      the apical K channel is mediated by stimulation of P(2)Y(2) receptors and results
      from increasing dephosphorylation by enhancing PKG-sensitive phosphatase
      activity.

PMID- 10919876
TI  - Does levodopa improve visual function in NAION?

PMID- 10919877
TI  - Does Levodopa improve visual function in NAION?

PMID- 10919878
TI  - Does Levodopa improve visual function in NAION?

PMID- 10919879
TI  - Author's reply

PMID- 10919880
TI  - Author's reply

PMID- 10919881
TI  - Supervision during automated perimetry.

PMID- 10919882
TI  - Author's reply

PMID- 10919883
TI  - Supervision during automated perimetry.

PMID- 10919884
TI  - Uveal melanoma: a rare malignancy.

PMID- 10919885
TI  - Tumor doubling times in metastatic malignant melanoma of the uvea: tumor
      progression before and after treatment.
AB  - OBJECTIVE: To obtain estimates of growth rate of metastatic uveal melanoma to
      infer appropriate follow-up programs and to assess the impact of current
      chemoimmunotherapy regimens. DESIGN: Retrospective case series. PARTICIPANTS: Of
      70 consecutive patients diagnosed with metastatic uveal melanoma from 1986
      through 1998, 37 patients who attended regular follow-up and had measurable
      metastases were eligible for this study. METHODS: Tumor doubling time (DT) was
      calculated by the Schwartz formula using three presumed sizes of metastasis at
      last negative follow-up. DT was compared according to tumor characteristics, and
      time of micrometastasis was estimated. MAIN OUTCOME MEASURES: Doubling time of
      untreated and treated metastases. RESULTS: Doubling time of untreated metastases
      ranged from 34 to 220 days (median, 63 days). Regardless of the presumed size of
      metastasis at last screening, two thirds of the metastases had a DT between 30
      and 80 days. No significant correlation between DT and the observed disease-free
      interval was detected. Assuming constant growth rate, most metastases had
      predictably initiated within 5 years before primary treatment. Mean DT during
      active treatment of metastases in 18 patients who did not show an objective
      response ranged from 25 to 2619 days (median, 255 days). CONCLUSIONS: Based on
      the estimated growth rates, a rational follow-up interval to detect metastatic
      uveal melanoma would be 4 to 6 months. Primary uveal melanomas that develop
      clinically detectable metastasis after conservative therapy may micrometastasize
      several years before treatment. These estimates are rough and must be confirmed
      by prospective studies. Current chemoimmunotherapy regimens slow down the growth
      rate of metastases even if objective response is not obtained.

PMID- 10919886
TI  - Periorbital and orbital cellulitis before and after the advent of Haemophilus
      influenzae type B vaccination.
AB  - OBJECTIVE: To evaluate the effect of the introduction of the Haemophilus
      influenzae B (Hib) vaccine (introduced first in 1985, then extended in 1990 to
      children at least 2 months of age) on the epidemiologic features of periorbital
      and orbital cellulitis. DESIGN: Retrospective, comparative case series.
      PARTICIPANTS: Three hundred fifteen pediatric inpatients. METHODS: Children at
      Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary with
      discharge diagnosis of periorbital or orbital cellulitis from 1980 through 1998
      were reviewed. MAIN OUTCOME MEASURES: Case rate, culture-positive isolates, and
      associated conditions. RESULTS: A total of 297 cases of periorbital cellulitis
      and 18 cases of orbital cellulitis were reviewed. Before 1990, there were 27
      cases of Hib-related cellulitis (11.7% of total in that period), whereas after
      1990, there were only three (3.5% of total; P = 0.028). The number of cases per
      year was significantly lower after 1990 (21.2 +/- 10.4 vs. 8.7 +/- 3.9; P =
      0.008), as were the number of positive culture isolates (for any organism) after
      1990 (76 [33. 0%] vs. 9 [10.6%]; P < 0.001). The medical conditions most commonly
      associated with periorbital cellulitis were sinusitis (44 [14.5%]) and upper
      respiratory infections (73 [26.6%]). All cases of orbital cellulitis were
      associated with sinusitis. CONCLUSIONS: The introduction of the Hib vaccine
      coincided with a sharp decline not only in the number of periorbital and orbital
      cellulitis cases related to H. influenzae, but also in the annual case rate.
      These data are consistent with a facilitative role for H. influenzae in the
      development of cellulitis secondary to other pathogens. They also may support
      restriction of the spectrum of antibiotics used to manage these conditions.

PMID- 10919888
TI  - Discussion by

PMID- 10919887
TI  - Criteria for nonsurgical management of subperiosteal abscess of the orbit:
      analysis of outcomes 1988-1998.
AB  - PURPOSE: On the basis of bacteriologic studies, we have recommended expectant
      observation with intravenous antibiotics for subperiosteal abscess (SPA) of the
      orbit in patients less than 9 years of age, given the absence of eight other
      specific surgical criteria. We attempted to test these recommendations with a
      prospective study. STUDY DESIGN: Prospective noncomparative case series.
      PARTICIPANTS: Forty patients younger than 9 years of age treated for orbital SPAs
      at the Childrens Hospital of Wisconsin from 1988 to 1998. METHODS: Specific
      management criteria were applied to a cohort of 37 orbital SPA patients. Three
      other orbital SPA patients under the age of 9, either ineligible for medical
      therapy or treated outside our guidelines, were also studied. Clinical data for
      all patients were reviewed and analyzed. MAIN OUTCOME MEASURES: Clinical
      resolution of the abscess, as evidenced by normal visual acuity, pupillary
      examination, motility, and globe position on the affected side. RESULTS: Eight
      patients met criteria for surgical treatment and underwent prompt drainage. Of
      the 29 patients for whom initial nonsurgical management was recommended, 27
      (93.1%) SPAs cleared with expectant observation on intravenous antibiotics, and 2
      patients defaulted to surgical intervention. All cases had successful clinical
      outcomes. CONCLUSIONS: In patients less than 9 years of age, orbital SPAs are
      likely to resolve without surgery, provided certain surgical criteria are absent.

PMID- 10919889
TI  - Transcaruncular approach to the medial orbit and orbital apex.
AB  - OBJECTIVE: To present a versatile approach to the medial orbit and orbital apex
      through the caruncle. DESIGN: Retrospective, noncomparative, case series with
      description of surgical technique. PARTICIPANTS: Twenty-five consecutive patients
      underwent orbital surgery by use of a transcaruncular approach. INTERVENTION:
      Inferior and medial wall fracture repair or orbital decompression by means of a
      transcaruncular or combined transfornix-transcaruncular approach. MAIN OUTCOME
      MEASURES: The surgical indications and complications were recorded for each
      patient. RESULTS: Ten patients (10 orbits) underwent combined inferior and medial
      orbital wall fracture repair through a combined transfornix-transcaruncular
      approach. In 8 of 10 (80%) orbits, the inferior oblique muscle was disinserted
      during surgery. Fifteen patients (24 orbits) underwent orbital decompression
      surgery for dysthyroid orbitopathy. An isolated transcaruncular approach was used
      in 5 of 24 orbits, and a combined transfornix-transcaruncular approach was used
      in 19 of 24 orbits. There were no complications related to either approach.
      CONCLUSIONS: Orbital bone removal and fracture reduction may be safely completed
      through a combined transfornix-transcaruncular approach. The transcaruncular
      approach provides excellent and safe exposure of the medial orbital wall, and it
      avoids scarring associated with the Lynch approach.

PMID- 10919891
TI  - Teleophthalmology: the use of real-time telementoring to remove an orbital tumor.
AB  - OBJECTIVE: To determine whether current telemedicine technology can support real
      time surgical telementoring to remove an orbital tumor. DESIGN: Interventional
      case report METHODS: An orbital specialist guided a general ophthalmologist in
      the removal of a lateral orbital tumor from a site 210 miles away on another
      island. A 3-mm endoscope connected to a three-chip digital video camera attached
      to a Concorde 4500 Picture-Tel videoconferencing system was used to transmit
      images at a rate of 384 kb per second over integrated service digital network
      lines. MAIN OUTCOME MEASURES: Successful performance and outcome of the
      telementored procedure comparable to hands-on orbital surgery. RESULTS: The
      surgical procedure was successfully telementored with uncomplicated removal of
      the orbital tumor. CONCLUSIONS: Current telemedicine technology can support real
      time telementoring to remove an orbital tumor.

PMID- 10919890
TI  - Sarcomatous transformation of the orbit in a patient with Paget's disease.
AB  - OBJECTIVE: To report the clinical and pathologic features of sarcomatous
      transformation of the skull with involvement of the orbit, in Paget's disease.
      DESIGN: Interventional case report. PARTICIPANT: An 83-year-old woman with
      Paget's disease who experienced progressive proptosis of the left eye.
      INTERVENTION: Fine-needle aspiration biopsy of the orbital mass. RESULTS:
      Cytologic examination revealed round to oval malignant cells with wispy
      cytoplasm, consistent with the diagnosis of sarcoma. The patient died shortly
      after institution of orbital radiation therapy and systemic steroid therapy.
      CONCLUSIONS: Proptosis related to Paget's disease is uncommon, and only rarely is
      it a result of sarcomatous transformation. Sarcomatous transformation of the
      skull involving the orbit should be included in the differential diagnosis of
      progressive proptosis in patients with Paget's disease.

PMID- 10919892
TI  - Air bag-associated ocular trauma in children.
AB  - OBJECTIVE: To describe a series of children with ocular injuries related to air
      bag deployment. DESIGN: Retrospective, observational case series. PARTICIPANTS:
      Seven patients with ocular injuries sustained in motor vehicle accidents in which
      air bags were deployed. METHODS: Review of medical records. RESULTS: All patients
      had periocular contusions. Minor injuries included corneal abrasions (n = 5),
      superficial eyelid laceration (n = 1), and traumatic iritis (n = 2). Serious
      injuries included corneal edema (n = 1) and a traumatic hyphema with secondary
      glaucoma and cataract (n = 1). The latter patient required surgery. All other
      injuries resolved with medical therapy. All patients recovered normal visual
      acuity. CONCLUSIONS: Serious ocular injuries in children may result from air bag
      deployment. Most such injuries are minor and resolve without sequela. It is
      recommended that infants and children travel in the rear seat of automobiles to
      minimize their risk of injury.

PMID- 10919893
TI  - Recurrent isolated ptosis in presumed ophthalmoplegic migraine of childhood.
AB  - PURPOSE: To report a rare case of isolated, recurrent unilateral eyelid ptosis as
      the sole manifestation of ophthalmoplegic migraine in a healthy young girl.
      DESIGN: Single observational case report with review of the literature. TESTING:
      Serologic evaluation, electromyographic, nerve conduction and Tensilon testing,
      magnetic resonance and computerized tomographic imaging, and magnetic resonance
      angiography were performed. MAIN OUTCOME MEASURES: Four-year descriptive history
      of recurrent eyelid ptosis. RESULTS: Between 1994 and 1998, seven discrete
      episodes of right upper eyelid ptosis without ophthalmoplegia or pupil
      abnormality occurred. On each occasion, spontaneous resolution occurred over a
      period of 6 to 10 weeks. Extensive clinical and laboratory evaluation, including
      testing for myasthenia gravis and magnetic resonance cerebral angiography, was
      unremarkable. CONCLUSIONS: Recurrent isolated ptosis is a rare manifestation of
      presumed ophthalmoplegic migraine in childhood. As far as we are aware, this has
      not been previously reported.

PMID- 10919894
TI  - Iris lymphoma in a pediatric cardiac transplant recipient: clinicopathologic
      findings.
AB  - PURPOSE: To report the unusual presentation of a confirmed iris lymphoma in the
      setting of posttransplant lymphoproliferative disorder. DESIGN: Case report with
      clinicopathologic findings. METHODS: The medical record was reviewed for clinical
      manifestations, course of disease, and pathologic and radiologic findings.
      RESULTS: A 4-year-old girl who had undergone a cardiac transplant at 3 months of
      age was found to have unilateral iris lesions associated with granulomatous
      uveitis. Her condition was unresponsive to local and systemic steroids, so she
      underwent an iris biopsy that was found to contain a B cell-derived monoclonal
      lymphoproliferation. Treatment with systemic chemotherapy including
      cyclophosphamide and prednisone resulted in a transient, partial response.
      Localized radiotherapy induced total regression of the iris lesions. She
      continues to be observed and has been free of recurrence or metastasis for the
      past 12 months. CONCLUSIONS: Because of the increased use of organ
      transplantation, eye care specialists should consider the diagnosis of
      intraocular lymphoma when confronted with uveitis-like syndrome unresponsive to
      topical steroid therapy. Although there are numerous treatment options for
      intraocular lymphoma, radiation therapy was found to be effective in the
      treatment of this case.

PMID- 10919896
TI  - Brown recluse spider bite to the eyelid.
AB  - PURPOSE: To present a photographically documented case of a known brown recluse
      spider bite to the eyelid. DESIGN: Interventional case report. METHODS: The wound
      was photographed daily during an 11-day hospitalization and at 1 month and 6
      months after the injury. Treatment included canthotomy and cantholysis;
      administration of dapsone, antibiotics, and steroids; and hyperbaric oxygen
      therapy. MAIN OUTCOME MEASURES: Clinical presentation and course of a known brown
      recluse spider bite. RESULTS: Complete recovery with cicatrization at the site of
      the bite. CONCLUSIONS: We present a case of a brown recluse spider bite to the
      left lower eyelid with a discussion of management and outcome of this rarely
      reported injury.

PMID- 10919895
TI  - Endogenous bacterial endophthalmitis: an east Asian experience and a reappraisal
      of a severe ocular affliction.
AB  - PURPOSE: To report 32 eyes of 27 patients with endogenous bacterial
      endophthalmitis seen over a 4 year period. Features and outcomes of this
      condition in the current series and the cases reported in the literature from
      1986-1998 were reviewed. DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: All patients with this condition seen at the three participating
      general hospitals were included. INTERVENTION: A review of the systemic and
      ocular characteristics, therapeutic methods, and final outcomes in patients
      afflicted with this condition. MAIN OUTCOME MEASURES: Features studied included
      patients' demographic characteristics, microbiology, source of infection, ocular
      features, therapeutic interventions, final visual and anatomic outcomes. RESULTS:
      Nineteen (70%) of the 27 incriminating organisms in this case series were gram
      negative microbes, with Klebsiella pneumoniae infections alone being responsible
      in 16 (60%) cases. Hepatobiliary tract infection was the source of bacteremia in
      13 (48%) patients. Only nine (28%) eyes obtained good final visual acuity (20/120
      or better), and two eyes were enucleated/eviscerated. A literature review of 209
      patients with endogenous endophthalmitis over a 12 year period showed a similar
      increase in the frequency of gram negative microbes as the responsible organism,
      especially among the East Asian population. Overall, 22% had bilateral
      involvement; two thirds of patients had predisposing factor(s) or underlying
      illness(es), and diabetes mellitus was present in 46%. Thirty-four percent of all
      eyes obtained counting finger or better final vision, and 16% had their eyes
      eviscerated or enucleated. Infections with virulent organisms (gram negative
      rods, Serratia, Bacillus) usually denoted a grave visual prognosis; however, a
      media that was not opaque on presentation was usually associated with a good
      prognosis. CONCLUSION: Metastatic ocular infection is not uncommon despite the
      availability of modern antibiotic therapy. Among the East Asian population, the
      patient at highest risk is a diabetic patient with Klebsiella pneumoniae
      hepatobiliary infection. In contrast, in the Caucasian population, this condition
      occurs in predisposed patients with gram-positive bacteremia arising from
      endocarditis or skin/joint infections. The final visual outcome in patients with
      endogenous bacterial endophthalmitis in the recent 12 years has not differed
      significantly from five decades ago.

PMID- 10919897
TI  - Shifting trends in bacterial keratitis in south Florida and emerging resistance
      to fluoroquinolones.
AB  - OBJECTIVE: To study the distribution, current trends, and patterns of resistance
      to antimicrobial agents of bacterial keratitis isolates in South Florida. DESIGN:
      Retrospective, observational, case series. PARTICIPANTS: The microbiology records
      of all patients with bacterial keratitis seeking treatment at the Bascom Palmer
      Eye Institute from January 1, 1990 through December 31, 1998 were reviewed. MAIN
      OUTCOME MEASURES: In vitro laboratory minimum inhibitory concentration testing of
      the corneal isolates to the fluoroquinolones (ofloxacin and ciprofloxacin) and to
      the aminoglycosides (tobramycin and gentamicin) was performed using the Vitek
      (Automatic Microbial System Biomerieux Vitek, Inc., Hazelwood, Missouri) method.
      RESULTS: During this 9-year period, 2920 consecutive corneal cultures were
      obtained, and a pathogen was recovered in 1468 cultures (50%). The number of
      corneal ulcers scraped, positive cultures, recovered bacterial isolates, and
      ratio of gram-positive to gram-negative isolates per year remained approximately
      equal throughout the study period. Staphylococcus aureus and Pseudomonas
      aeruginosa represented 19.4% and 25.7%, respectively, of the total bacterial
      isolates during this period. However, we documented a gradual increase in the
      number of S. aureus keratitis isolates (29% of gram-positive organisms in 1990
      versus 48% in 1998, P = 0.01) coupled with a decrease in the number of P.
      aeruginosa isolates (54% of gram-negative organisms in 1990 versus 46% in 1998).
      A decrease in the incidence of contact lens-associated keratitis and P.
      aeruginosa isolates in this group of patients was documented. Serratia marcescens
      and P. aeruginosa were most commonly isolated in contact lens-associated
      keratitis (18% each). There was increasing laboratory resistance of S. aureus
      keratitis isolates to the fluoroquinolones (11% in 1990 to 28% in 1998), but
      resistance patterns to the aminoglycosides remained unchanged. There was a three
      fold increase in the percentage of resistant S. aureus isolates to
      fluoroquinolones between 1990 and 1994 and between 1995 and 1998. Both
      fluoroquinolones and aminoglycosides exhibited low in vitro effectiveness against
      P. aeruginosa throughout the study period. CONCLUSIONS: The increased recovery of
      S. aureus keratitis isolates and decreased laboratory effectiveness against
      fluoroquinolones to these pathogens present an important therapeutic challenge.

PMID- 10919898
TI  - Capnocytophaga keratitis.
AB  - PURPOSE: To review the clinical course, treatment, and visual outcomes of
      keratitis caused by the gram negative rod CAPNOCYTOPHAGA: DESIGN: Retrospective,
      noncomparative case series. PARTICIPANTS: Ten patients with culture-proven
      unilateral CAPNOCYTOPHAGA: keratitis examined at the Bascom Palmer Eye Institute
      between January 1, 1989, and December 31, 1998. INTERVENTION: All patients
      underwent standard diagnostic microbiologic evaluation, and topical antimicrobial
      therapy was instituted. A penetrating keratoplasty or enucleation was performed
      in some patients. MAIN OUTCOME MEASURES: The changes in visual acuity and
      clinical response to antimicrobial therapy. RESULTS: Predisposing factors were
      present in all patients. Cultures identified CAPNOCYTOPHAGA: species at a mean of
      7.5 days. Initial topical treatment consisted of an aminoglycoside and vancomycin
      in four patients, a quinolone or aminoglycoside alone in two patients each, and
      ofloxacin with vancomycin or tobramycin with ceftazidime in one patient each.
      After the microbiologic identification of CAPNOCYTOPHAGA:, treatment in four
      patients was changed to intensive, topical clindamycin. Five of the 10 eyes were
      medically cured (3 of these eyes underwent penetrating keratoplasty for corneal
      scarring), and 5 eyes required enucleation. The indications for enucleation
      included persistent infection with development of endophthalmitis or blind,
      painful eye. Five of the 10 eyes achieved 20/80 or better final visual acuity.
      Four of these five eyes were treated with topical clindamycin. CONCLUSIONS:
      Important factors in achieving a good visual outcome in CAPNOCYTOPHAGA: keratitis
      include early microbiologic identification and intensive therapy with topical
      clindamycin. CAPNOCYTOPHAGA: should be included in the differential diagnosis of
      bacterial keratitis in patients with suggestive predisposing factors or with
      protracted keratitis unresponsive to treatment.

PMID- 10919899
TI  - Comparison of the efficacy and safety of valaciclovir and acyclovir for the
      treatment of herpes zoster ophthalmicus.
AB  - OBJECTIVE: To compare the efficacy and safety of valaciclovir and acyclovir in
      immunocompetent patients with herpes zoster ophthalmicus. DESIGN: A multicenter,
      randomized, double-masked study. PARTICIPANTS: One hundred ten immunocompetent
      patients with herpes zoster ophthalmicus diagnosed within 72 hours of skin
      eruption were treated; 56 were allocated to the valaciclovir group and 54 to the
      acyclovir group. METHODS: Patients randomized to the valaciclovir group received
      two 500-mg tablets of valaciclovir three times daily and one tablet of placebo
      twice daily. Patients in the acyclovir group received one 800-mg tablet of
      acyclovir five times daily and one tablet of placebo three times daily for 7
      days. MAIN OUTCOME MEASURES: Main outcome measures included the frequency,
      severity, and duration of ocular complications, patient reports of zoster
      associated pain, and the outcome of skin lesions. Tolerance was also assessed on
      the incidence and types of adverse effects and changes in laboratory parameters.
      The analysis was mainly descriptive and performed on an intent-to-treat basis.
      RESULTS: Ocular complications of herpes zoster ophthalmicus were similar in the
      valaciclovir and acyclovir treatment groups. The main complications were
      conjunctivitis (54% and 52%, respectively), superficial keratitis (39% and 48%,
      respectively for punctate keratitis; 11% in each group for dendritic keratitis),
      stromal keratitis (13% in each group), and uveitis (13% and 17%, respectively).
      The long-term outcomes of these ocular complications were favorable and similar
      in both treatment groups. Pain duration and severity and outcome of skin lesions
      were similar between groups. Most patients reported prodromal pain. After 1
      month, 25% of patients in the valaciclovir group and 31% in the acyclovir group
      still reported pain. The percentage of patients experiencing postherpetic
      neuralgia decreased during follow-up. The tolerance to acyclovir and valaciclovir
      was comparable and considered good. The most frequent adverse events were
      vomiting and edema of the eyelids or face (3%-5%). Three serious adverse events
      not linked to the study drugs occurred. CONCLUSIONS: Valaciclovir is as effective
      as acyclovir in preventing ocular complications of herpes zoster ophthalmicus,
      including conjunctivitis, superficial and stromal keratitis, and pain.
      Tolerability of the two drugs is similar, but the dosing schedule of valaciclovir
      is simpler.

PMID- 10919900
TI  - A randomized, double-masked trial of topical ketorolac versus artificial tears
      for treatment of viral conjunctivitis.
AB  - OBJECTIVE: To determine if topical ketorolac 0.5% relieves the symptoms and signs
      of viral conjunctivitis better than artificial tears. DESIGN: Randomized,
      controlled trial. PARTICIPANTS: One hundred seventeen patients with a clinical
      diagnosis of viral conjunctivitis were randomized to the treatment group or
      control group. METHODS: Physicians and patients were masked to treatment.
      Patients in the treatment group received topical ketorolac 0.5% four times daily.
      Patients in the control group received artificial tears four times daily. Symptom
      and sign scores were recorded on the day of recruitment and at the time of a
      follow-up examination 3 to 4 days later. MAIN OUTCOME MEASURES: Change in six
      symptoms of conjunctivitis (overall discomfort, itching, foreign body sensation,
      tearing, redness, and lid swelling) and four signs of conjunctivitis
      (conjunctival injection, conjunctival chemosis, conjunctival mucus, and lid
      edema). Adverse effects were also studied. RESULTS: A total of 105 patients
      returned for their 3- to 4-day follow-up. Both the artificial tear and ketorolac
      groups showed improvement in all symptom scores at their 3- to 4-day follow-up
      visit. There was no statistically significant difference between the change in
      symptom scores between the treatment group and control group in any symptom
      category except redness. Patients in the control group were more likely to report
      improvement in redness than those in the treatment group, P = 0.012. There was no
      statistically significant difference between the change in sign scores between
      the treatment and control groups. Ketorolac 0.5% was more likely to produce
      stinging than artificial tears, 59.2% versus 18.8%, P < 0.001. CONCLUSIONS:
      Topical ketorolac 0.5% used four times daily is no better than artificial tears
      at relieving the symptoms or signs of viral conjunctivitis and produces more
      stinging than artificial tears.

PMID- 10919902
TI  - Discussion by

PMID- 10919901
TI  - Association of preoperative tear function with surgical outcome in severe Stevens
      Johnson syndrome.
AB  - OBJECTIVE: To retrospectively study the surgical outcome in severe Stevens
      Johnson syndrome (SJS). DESIGN: Retrospective noncomparative case series.
      PARTICIPANTS: Twenty-nine eyes of patients with severe SJS associated with total
      conjunctivalization were examined. INTERVENTION: Preserved human amniotic
      membrane grafting and keratolimbal allograft transplantation was performed.
      Intensive immunosuppression and epithelial management were continued
      postoperatively. MAIN OUTCOME MEASURES: Successful ocular surface reconstruction
      was determined by epithelialization with corneal epithelium. The association
      between surgical outcome and preoperative tear function was studied. RESULTS: The
      ocular surface was successfully covered by corneal epithelium in 13 eyes (44.8%).
      The mean corrected visual acuity recovered from 0.0039 to 0.017. Persistent
      epithelial defect was the most common complication. Eyes with successful ocular
      surface reconstruction had significantly better preoperative Schirmer's test
      values (P = 0.025) and tear clearance rates (P = 0.043) than those that failed.
      CONCLUSIONS: In patients with severe SJS, preoperative tear function
      significantly influenced surgical outcome. Eyes with Schirmer's test value of >10
      mm have a greater chance of successful ocular surface reconstruction.

PMID- 10919904
TI  - The refractive status and vision profile: a questionnaire to measure vision
      related quality of life in persons with refractive error.
AB  - OBJECTIVE/BACKGROUND: To describe the Refractive Status and Vision Profile
      (RSVP), a questionnaire that measures self-reported vision-related health status
      (symptoms, functioning, expectations, concern) in persons with refractive error.
      DESIGN: Cross-sectional study by survey. PARTICIPANTS: The RSVP was self
      administered by 550 participants with refractive error (or history of refractive
      surgery) recruited from five refractive surgery practices and one optometric
      practice. Information on refraction, uncorrected and best-corrected visual
      acuity, and history of refractive surgery was obtained from physicians' records.
      METHODS: Internal consistency, test-retest reliability, agreement with global
      measures of vision (criterion validity), discriminant validity, content validity,
      and construct validity (associations of scale scores with patient status
      variables) were assessed using Cronbach's alpha, Spearman rank correlations,
      factor analysis, and multitrait analysis. OUTCOME MEASURES: Scores on the overall
      RSVP scale (S) and on eight RSVP subscales (functioning, driving, concern,
      expectations, symptoms, glare, optical problems, problems with corrective lenses)
      were calculated based on 42 items. RESULTS: Cronbach's alpha was 0.92 for S and
      ranged from 0.70 to 0.93 for RSVP subscales, indicating good internal
      consistency. Satisfaction with vision was more strongly associated with S than
      with refractive error or with visual acuity. Individuals with more refractive
      error had significantly lower (worse) scores for S and for subscales concern,
      functioning, driving, optical problems, and glare. Scores for S and for subscales
      concern, functioning, optical problems, and driving remained significantly
      associated with satisfaction with vision after adjustment for age, gender,
      corrective lens type, and refractive error. CONCLUSIONS: The RSVP measures a
      range of visual, functional, and psychologic impacts of refractive error that are
      likely to be important to patients. The RSVP would be a useful tool for
      evaluating interventions for correction of refractive error and may be useful for
      assessing refractive surgery candidates in clinical practice.

PMID- 10919903
TI  - Linear IgA bullous disease limited to the eye: a diagnostic dilemma: response to
      intravenous immunoglobulin therapy.
AB  - PURPOSE: To report on a diagnostic dilemma and treatment challenge in a patient
      with chronic cicatrizing conjunctivitis without involvement of skin and other
      mucous membranes persisting for 6 years and not responding to topical and
      systemic steroids. DESIGN: Interventional case report. METHODS: We performed
      direct immunofluorescence of the conjunctiva with fluorescein-conjugated rabbit
      antihuman antibodies against immunoglobulin A, G, and M, complement 3 component,
      and fibrinogen. To investigate the presence of circulating antibodies in
      patient's serum, indirect immunofluorescence using normal human conjunctiva,
      normal human skin, and monkey esophagus as substrate was done. In addition, we
      did immunoblot analysis using normal human epidermis as substrate to determine
      the molecular weight of an antigen. The patient was treated with intravenous
      immunoglobulin (IVIg). The correlation between the titer of circulating
      antibodies and the activity of conjunctival inflammation at various intervals
      during the course of IVIg therapy was demonstrated by immunoblot assay with
      serial dilutions of the patient's serum. The highest dilution at which the
      binding was visible was considered the titer. RESULTS: Direct immunofluorescence
      of the conjunctiva and indirect immunofluorescence with both salt split skin and
      conjunctiva as substrate disclosed linear deposition of immunoglobulin A (IgA) at
      the epithelial basement membrane. Immunoblot analysis demonstrated the presence
      of IgA circulating antibodies in patient's serum directed against a 97kDa protein
      in human epidermis. A continuous decrease in the titer of these antibodies
      correlating to improvement of clinical symptoms was observed during IVIg therapy.
      CONCLUSIONS: Use of a nonconventional diagnostic tool (immunoblot analysis), in
      addition to conventional immunohistologic studies, might be helpful in
      establishing the diagnosis of patients with chronic cicatrizing conjunctivitis.
      On the basis of results of these laboratory tests and clinical presentation, we
      believe that this patient has linear IgA bullous disease limited to the eye. IVIg
      therapy decreased the titer of circulating antibodies and induced a remission in
      this patient.

PMID- 10919905
TI  - Refractive lensectomy for hyperopia.
AB  - PURPOSE: The purpose of this study was to evaluate refractive lensectomy as a
      surgical procedure for the treatment of hyperopia. DESIGN: A retrospective
      noncomparative case series. PARTICIPANTS: Twenty-nine patients were included in
      the study. Fifty eyes underwent extraction of the crystalline lens and
      intraocular lens implantation. METHODS: Operations were performed by the same
      surgeon with the patient under general anesthetic. All lenses were removed by
      phacoemulsification with insertion of lens implants singly or as piggyback
      lenses. The Holladay2 formula was used to calculate lens powers. Results are
      compared with other methods of treating hyperopia. MAIN OUTCOME MEASURES: The
      main parameters assessed were safety, efficacy, predictability, stability, and
      complications. RESULTS: Eyes were divided into group A (n = 26), with an average
      preoperative spherical equivalent (SE) of +2.26 +/- 0.94, and group B (n = 24),
      with an average preoperative SE of +6.32 +/- 1.32. In group A, after refractive
      lensectomy, 80.7% had no change in best-corrected visual acuity (BCVA) or gained
      a line, whereas 11.5% lost one line; 88.5% had an uncorrected visual acuity
      (UCVA) of 20/40 or better, and 88.5% were within 1 diopter (D) of intended
      postoperative SE. In group B, 70.9% of eyes had no change or gained a line in
      BCVA, whereas 29.2% lost a line of BCVA; 62.5% had UCVA of 20/40 or better
      postoperatively, and 58.3% were within 1 D of the intended SE. In one eye the
      posterior capsule was breached intraoperatively. One eye had a symptomatic
      episode of cystoid macula edema that settled spontaneously. To date, seven eyes
      have required secondary refractive procedures, and three eyes have required
      yttrium-aluminum-garnet capsulotomy. CONCLUSIONS: In the presbyopic age group
      refractive lensectomy may be a realistic alternative to photorefractive
      keratectomy or laser in situ keratomileusis, with certain potential advantages.

PMID- 10919906
TI  - Myopic angle-supported intraocular lenses: two-year follow-up.
AB  - OBJECTIVE: To evaluate clinical and refractive results of myopic angle-supported
      intraocular lenses (IOLs). DESIGN: Prospective, noncomparative case series.
      PARTICIPANTS: Twenty-one eyes of 12 patients (7 female) with a mean age of 29.5
      years and a follow-up of 24 months. The prospective study included highly myopic
      eyes (more than -11.00 diopters [D]) with spectacle-corrected visual acuity
      better than 20/200. METHODS: Twenty-one eyes underwent implantation of a single
      piece IOL with Z-shaped haptics for angle support (each haptic with two
      footplates) and an optical zone of 4.5 mm (NuVita, Bausch & Lomb Surgical,
      Irvine, CA). The dioptric power of the IOL was calculated considering refraction,
      keratometry, and anterior chamber depth (specific nomogram), and its diameter was
      determined by adding 0.5 mm to the corneal diameter. MAIN OUTCOME MEASURES: We
      evaluated the following clinical and refractive data: visual acuity without and
      with correction (VAsc and VAcc), spherical equivalent (SE) obtained under
      cycloplegia, slit-lamp biomicroscopy, keratometry, applanation tonometry,
      endothelial cell count, ultrasound pachymetry, gonioscopy, indirect
      ophthalmoscopy, subjective complaints, and descriptions of complications.
      RESULTS: Mean postoperative VAsc was 20/74. Mean preoperative VAcc (20/50)
      increased to 20/30; 65% gained at least two lines of VAcc, and no eye had a
      decrease in VAcc. Preoperative SE (-18.95 D) evolved to -2. 06 D, stabilizing
      after one month. Iris retraction (pupil ovalization) more than 0.5 mm was noted
      in eight eyes (40%). Mean keratometry, corneal astigmatism, and ultrasound
      pachymetry were stable during the study (P > 0.01). Significant endothelial cell
      loss was demonstrated in the second year. Gonioscopy showed 70 (87. 5%)
      footplates ideally positioned with no iris depression. Reports of glare and
      haloes in dark environment were considered light in 80% and not referred in 20%,
      and spectacles were used for residual refraction in 75%. Intraocular lens
      exchange was needed in one eye because of undersizing, and the IOL was removed in
      one eye because of chronic inflammatory reaction associated with ocular
      hypertension (this patient was excluded from the statistical analysis).
      CONCLUSIONS: This report demonstrates good efficacy for correction of high myopia
      by the phakic IOL used during the two years of follow-up. Long-term complications
      (safety) such as iris retraction and endothelial cell loss remain a concern.

PMID- 10919907
TI  - Relative anterior microphthalmos: morphometric analysis and its implications for
      cataract surgery.
AB  - PURPOSE: To evaluate morphometric data and risk factors for complications of
      cataract surgery in patients with relative anterior microphthalmos (RAM). DESIGN:
      Retrospective, comparative study (Part I) and matched pairs analysis with
      controls (Part II). PARTICIPANTS: Sixty-two patients with RAM who underwent
      cataract surgery at the Department of Ophthalmology, Ruprecht-Karls-University of
      Heidelberg, Germany, between 1989 and 1997. RAM is defined as eyes with
      horizontal corneal diameters </=11 mm, axial length of >20 mm, and no other
      morphologic malformation. MAIN OUTCOME MEASURES: Part I: Patients were examined
      preoperatively for anterior chamber (AC) depth, lens thickness, total axial
      length, and refraction. Associated ocular pathologic conditions (such as glaucoma
      or previous surgical interventions) were recorded. Part II: A matched pairs
      analysis concerning the anatomic features was performed with a group of 17
      patients with RAM and 17 patients (controls) that matched the RAM group in terms
      of axial length, age, and gender but showed corneal diameters >11 mm. RESULTS:
      Part I: Anatomic parameters in RAM showed an average corneal diameter of 10.7 +/-
      0.34 mm, AC depth of 2.20 +/- 0.49 mm, and average lens thickness of 5. 05 +/-
      0.45 mm. Fifty-five percent of the patients had myopic refraction. There was a
      high incidence of glaucoma (77.4%), cornea guttata (45.2%), and pseudoexfoliation
      syndrome (16.1%) in the RAM group. Sixty percent of patients had undergone
      previous glaucoma surgery. After cataract surgery, 51.2% of patients achieved a
      visual acuity of >20/40 and 69.8% of >20/50. Temporary corneal edema (54. 8%) and
      ciliolenticular block (11.6%) were the most important complications after
      cataract surgery. Part II: Matched pairs analysis showed significant differences
      between RAM and controls in terms of AC depth (P =0.029) but no difference in
      lens thickness (P = 0.12). CONCLUSIONS: Relative anterior microphthalmos can be
      characterized in terms of morphometric data as eyes with corneal diameters </=11
      mm and AC depths of 2 mm. The small anterior segment, especially the shallow
      anterior chamber, is responsible for the high incidence of glaucoma and
      postoperative complications after cataract surgery. Identifying these patients
      before surgery helps the cataract surgeon to be prepared for potential problems.

PMID- 10919909
TI  - Discussion by

PMID- 10919908
TI  - Unexpected corneal endothelial cell decompensation after intraocular surgery with
      instruments sterilized by plasma gas.
AB  - PURPOSE: Ten cases of unexpected corneal endothelial cell decompensation
      occurring after routine intraocular surgery using instruments sterilized with a
      new plasma gas protocol are described. DESIGN: A retrospective observational case
      series with 1 year of follow-up was conducted. RESULTS: All patients had corneal
      decompensation and nonreactive pupils after surgery. Six patients required
      penetrating keratoplasty. Three patients partially recovered pupillary function.
      Visual acuity at 1 year ranged from 20/20 to hand motion (HM). One patient with
      an anterior chamber intraocular lens (ACIOL) experienced optic atrophy and HM
      vision despite resolution of corneal edema. CONCLUSIONS: Toxic corneal
      endothelial cell destruction syndrome was associated with the introduction of
      plasma gas sterilization protocols.

PMID- 10919910
TI  - Effects of pterygium on corneal spherical power and astigmatism.
AB  - OBJECTIVE: To evaluate prospectively the corneal refractive status before and
      after pterygium surgery and its relationship with preoperative pterygium size.
      DESIGN: Prospective, nonrandomized, comparative (self-controlled) trial.
      PARTICIPANTS: One hundred thirty-six eyes undergoing primary pterygium removal
      surgery. MAIN OUTCOME MEASURES: Corneal spherical power, astigmatism, surface
      regularity index (SRI), and surface asymmetry index (SAI) before and after
      surgery, and the preoperative pterygium size. RESULTS: Before surgery, pterygium
      size significantly correlated with spherical power (Pearson's correlation
      coefficient, r = -0.370, P < 0.001), astigmatism (r = 0.600, P < 0.001), SRI (r =
      0.367, P < 0.001), and SAI (r = 0.387, P < 0.001). The surgery significantly
      increased spherical power of the cornea, whereas astigmatism, SRI, and SAI were
      significantly decreased by the surgery (P < 0.01, paired t test with Bonferroni's
      correction of P value for multiple comparison). Surgically induced changes in
      spherical power (r = 0.598, P < 0.001) and astigmatism (r = 0.653, P < 0.001)
      significantly correlated with the preoperative pterygium size. Precise prediction
      of the magnitude of refractive changes based on the preoperative pterygium size
      was difficult. CONCLUSIONS: The presence of pterygium and its removal
      significantly influence the corneal refraction including spherical power,
      astigmatism, asymmetry, and irregularity, with the larger pterygium exerting the
      greater influence.

PMID- 10919912
TI  - Discussion by

PMID- 10919911
TI  - One-year evaluation of myopic laser photoastigmatic refractive keratectomy using
      the summit apex plus: phase III of a Food and Drug Administration clinical trial.
AB  - PURPOSE: To prospectively evaluate the safety and efficacy of the Summit Apex
      Plus excimer laser in the treatment of primary compound myopic astigmatism.
      DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS:
      Patients with primary compound myopic astigmatism: sphere of -1.0 to -7.0
      diopters (D) and cylinder -1.0 to -5.0 D. METHODS: Ninety-three eyes of 56
      patients with a mean spherical equivalent of -4.98 +/- 1.80 D (-1.75 to -8.5)
      underwent photoastigmatic refractive keratectomy (PARK) with the Summit Apex Plus
      excimer laser using erodible mask technology. Prospective follow-up is analyzed
      at 1-year postoperatively. MAIN OUTCOME MEASURES: Postoperative reduction in
      myopic sphere, myopic astigmatism, spherical equivalent, angle of error,
      magnitude of error, difference vector, uncorrected visual acuity, and corneal
      haze. RESULTS: Seventy-one eyes were available at 1-year follow-up. Mean
      spherical equivalent was reduced 86.5% to a mean residual of -0. 65 D +/-0.70 D (
      2.88-+1.13 D). Astigmatism was reduced 66.2% to a mean residual of -0.76 +/- 0.52
      D (-2.25-0.00 D); 77.5% were within 1.0 D of attempted correction; 1.4% of eyes
      experienced an overcorrection >1.0 D of spherical equivalent; 0.27 D of mean
      myopic regression was demonstrated between 1 and 12 months; 93.0% of eyes
      achieved an uncorrected visual acuity of 20/40 or better; and 49.3% of eyes
      achieved an uncorrected visual acuity of 20/20 or better. CONCLUSIONS: PARK with
      the Summit Apex Plus excimer laser is effective at reducing compound myopic
      astigmatism. However, current laser algorithms result in consistent
      undercorrection of both the compound myopia and the astigmatic component.

PMID- 10919913
TI  - Topography-driven photorefractive keratectomy: results of corneal interactive
      programmed topographic ablation software.
AB  - OBJECTIVE: This study evaluated the efficacy, predictability, stability, and
      safety of a software program (Corneal Interactive Programmed Topographic Ablation
      (CIPTA) LIGI, Taranto, Italy) which, by transferring programmed ablation from the
      corneal topography to a flying-spot excimer laser, provides customized laser
      ablation. DESIGN: Noncomparative consecutive case series. PARTICIPANTS: Forty-two
      eyes of 34 subjects with a mean age of 33.9 (range, 20-54) had CIPTA at the
      Cattedra di Ottica Fisiopatologica of Bari (Italy). Twenty-eight eyes were
      treated for hyperopic astigmatism and 14 for myopic astigmatism. All the subjects
      had irregular astigmatism. OPERATION: Topography was acquired by a corneal
      topography mapping system (Orbscan, Orbtek, Inc., Salt Lake City, UT). These data
      were processed to obtain a customized altimetric ablation profile, which was
      transferred to a flying-spot laser (Laserscan 2000, Lasersight, Orlando, FL).
      MAIN OUTCOME MEASURES: Data on uncorrected (UCVA) and best-corrected visual
      acuity (BCVA), predictability, and stability of refraction and any complications
      were analyzed. RESULTS: Mean follow-up was 13.2 months. At the last postoperative
      examination, 26 eyes (92.8%) in the hyperopic group and 12 eyes (85.7%) in the
      myopic group had an UCVA superior to 20/40. Twelve hyperopic eyes (42.8%) and
      five myopic eyes (35.7%) had a UCVA of 20/20. All patients fell between 1 diopter
      of attempted correction in the spherical equivalent. Only 1 (2.4%) of the 42
      eyes, belonging to the hyperopic group, lost 1 Snellen line of BCVA. We did not
      observe any decentration and/or haze after photorefractive keratectomy treatment
      or any irregularity in the flap-stroma interface in the three laser in situ
      keratomileusis operations performed in this study. CONCLUSIONS: The combination
      of topographic data with computer-controlled flying-spot excimer laser ablation
      is a suitable solution for correcting irregular astigmatism due to different
      causes.

PMID- 10919915
TI  - Discussion by

PMID- 10919914
TI  - Hyperhomocystinemia in patients with nonarteritic anterior ischemic optic
      neuropathy, central retinal artery occlusion, and central retinal vein occlusion.
AB  - OBJECTIVE: This study aimed to determine the prevalence of hyperhomocystinemia
      among patients with nonarteritic anterior ischemic optic neuropathy (NAION),
      central retinal artery occlusion (CRAO), or central retinal vein occlusion
      (CRVO). DESIGN: Retrospective, case-control study. PARTICIPANTS: The study cohort
      consisted of 74 consecutive patients with NAION, CRAO, or CRVO who were examined
      at the Retina or Neuro-ophthalmological Unit of the Tel-Aviv Sourasky Medical
      Center from 1998 through 1999. The control group consisted of 81 consecutive
      patients of similar gender and age with no history of these pathologic
      conditions. MAIN OUTCOME MEASURES: Plasma homocystine levels of all study
      participants were obtained. RESULTS: Eighteen of 40 patients (45%) with NAION and
      eight of 13 patients (61.5%) with CRAO had hyperhomocystinemia compared with
      three of 21 (14.3%) in the CRVO group (P < 0.001) and eight (9.8%) in the control
      group (P < 0.0001). Hypertension and ischemic heart disease were significantly
      more prevalent in the NAION patients with elevated plasma homocystine.
      CONCLUSIONS: Our findings suggest that hyperhomocystinemia is a risk factor for
      NAION and CRAO.

PMID- 10919916
TI  - The prevalence of age-related maculopathy: the visual impairment project.
AB  - PURPOSE: To determine the prevalence of age-related maculopathy (ARM) lesions in
      residents of the state of Victoria, Australia. DESIGN: Population-based cross
      sectional study. PARTICIPANTS: Total of 5147 residential and institutionalized
      persons aged 40 years and older, living in Victoria. METHODS: Participants were
      recruited through a cluster, stratified, random sampling from nine urban clusters
      and four rural clusters. The presence of ARM lesions was graded from color stereo
      fundus photographs as well as slit-lamp stereo biomicroscopy according to the
      International Classification and Grading System. MAIN OUTCOME MEASURES: The
      presence of ARM lesions. RESULTS: The mean age of participants was 60.2 years,
      and 55% were females. Gradable fundus photographs were available for at least one
      eye in 4345 (92%) of the participants. The weighted prevalence of neovascular age
      related macular degeneration (AMD) was 0.39% (95% confidence limits [CL] = 0.20,
      0.58), atrophic AMD was 0. 27% (95% CL = 0.04, 0.50), and total AMD was 0.68%
      (95% CL = 0.30, 1. 1). Prevalence of AMD was strongly related to age (P < 0.001).
      Prevalence of early ARM was 15.1% (95% CL = 13.7, 16.4). Large drusen, 125
      micrometer or more, were present in 6.3% of the participants. There was a higher
      prevalence of soft distinct drusen (7.5%) than soft indistinct drusen (4.3%).
      Retinal pigmentary abnormalities were present in 8.2% (95% CL = 7.2, 9.2). The
      prevalence of large drusen, soft drusen, and pigmentary abnormalities increased
      with age (P < 0. 001). Prevalence of retinal pigmentary abnormalities increased
      with increasing drusen size (P < 0.001). Soft indistinct drusen were more common
      in women aged 70 years or older (P < 0.001). Bilaterality of any ARM was strongly
      age related, and women appeared to have a higher risk of both bilateral early ARM
      and AMD. CONCLUSIONS: These data provide age- and gender-specific prevalence of
      ARM and its component lesions in an ethnically diverse Australian population.
      Early ARM and AMD prevalence rates increased sharply from ages 70 and 80 years,
      respectively, in all ethnic groups. These higher rates will continue to increase
      the importance of AMD as our population ages.

PMID- 10919917
TI  - A comparison of stereoscopic fluorescein angiography with indocyanine green
      videoangiography in age-related macular degeneration.
AB  - PURPOSE: To correlate features of indocyanine green (ICG) videoangiography with
      stereo film fluorescein angiography (FA) in the analysis of age-related macular
      degeneration (AMD). DESIGN: A retrospective study with concurrent comparison of
      two methods of assessment on one set of patients with AMD undergoing sequential
      FA-ICG videoangiography. METHODS: One hundred four patients with AMD who had
      undergone immediately sequential FA-ICG videoangiography were selected in a
      consecutive fashion from the photographic files of the Casey Eye Institute. Three
      interpreters independently graded in an unbiased fashion the FA features of AMD.
      These were compared with ICG videoangiography features of hypocyanescence (ICG
      videoangiography hypofluorescence), moderate or intense hypercyanescence (ICG
      videoangiography hyperfluorescence), or absence of fluorescence over background
      (ICG videoangiography isocyanescence). We also assessed ICG videoangiography
      features in the opposite eye of those with choroidal neovascularization (CNV) by
      FA in one eye by examining an additional 96 FA-ICG videoangiography scans. MAIN
      OUTCOME MEASURES: Outcomes were the ICG videoangiography characteristics of
      classic and occult CNV, serous pigment epithelial detachments (SPEDs) both with
      and without CNV, macular hemorrhage, and the comparative size of these features.
      RESULTS: There were 25 eyes that had significant macular hemorrhage by FA. Of
      these, the FA revealed CNV in its entirety under or near the hemorrhage in 11.
      The ICG examination revealed all 11 plus an additional 12 hypercyanescent
      features that were not visible by FA. Although 26 of 32 SPEDs had CNV by FA
      analysis, 31 of 32 had well-defined hypercyanescence under or at the SPED edge by
      ICG videoangiography. Eighty-seven percent of eyes with classic choroidal
      neovascular membranes (CCNV; 20 of 23) and 93% of eyes with fibrovascular pigment
      epithelial detachments (FVPED; 66 of 71) were hypercyanescent with distinct
      edges. Fifty percent of eyes with only late leakage of undetermined source (LLUS)
      were hypercyanescent, whereas 50% were isocyanescent on ICG videoangiography.
      There were four of 104 eyes in which ICG videoangiography revealed poorly defined
      hypercyanescent areas when, by FA, there were only drusen or elevated blocked
      fluorescence. Indocyanine green videoangiography revealed only three eyes with
      poorly defined hypercyanescence of 200 fellow eyes in patients with unilateral
      AMD. CONCLUSIONS: Indocyanine green videoangiography correlated fairly well with
      stereoscopic FA for the presence of CCNV or FVPED, but correlated poorly when
      LLUS was present. In certain cases where CNV was associated with SPED or macular
      hemorrhage, ICG videoangiography demonstrated features not apparent on FA.

PMID- 10919919
TI  - Discussion by

PMID- 10919918
TI  - A new approach to stage 3 macular holes.
AB  - PURPOSE: The purpose of this article is to demonstrate the feasibility of a
      surgical approach that might be possible in an office setting for idiopathic
      stage 3 macular holes. The posterior hyaloid of the vitreous and perihole tissue
      is enzymatically manipulated to create an atraumatic posterior vitreous
      separation and may stimulate cell proliferation to close macular holes. DESIGN:
      Prospective noncomparative interventional case series. PARTICIPANTS: Nine eyes of
      eight patients with idiopathic stage 3 macular holes were treated. METHODS: The
      patients were treated with an injection of 0.4 IU of autologous plasmin enzyme
      into the midvitreous cavity and lavage of the vitreous cavity with an infusion
      light pipe and vitreous cutter followed by filling 70% to 80% of the vitreous
      cavity with 14% C3F8 and head-down positioning. MAIN OUTCOME MEASURES: Posterior
      vitreous detachment, macular hole closure, and vision improvement. RESULTS: Eight
      of nine eyes showed a spontaneous posterior vitreous detachment. One eye required
      minimal suction of less than 50 mmHg to elevate the posterior hyaloid off the
      retinal surface. Eyes were followed for a minimum of 6 months. All holes closed,
      and there was an average visual acuity improvement of four lines. The average
      surgical time for this procedure was 20 minutes. CONCLUSIONS: Autologous plasmin
      enzyme-assisted vitreous surgery techniques can reduce operative time, expense,
      and patient inconvenience while maintaining excellent surgical results, which may
      allow office-based vitreous surgery for idiopathic stage 3 macular holes.

PMID- 10919920
TI  - Homocysteine and cardiovascular disease: cause or effect?
AB  - Both markedly and mildly elevated circulating homocysteine concentrations are
      associated with increased risk of vascular occlusion. Here we review possible
      mechanisms that mediate these effects. Inborn errors of homocysteine metabolism
      result in markedly elevated plasma homocysteine (200-300 micromol/L) and
      thromboembolic (mainly venous) disease: treatment to lower but not to normalize
      these concentrations prevents vascular events. Mild homocysteine elevation (>15
      micromol/L) occurs in approximately 20-30% of patients with atherosclerotic
      disease. Usually, this is easily normalized with oral folate and ongoing trials
      are assessing the effect of folate treatment on outcomes. Although there is
      evidence of endothelial dysfunction with both markedly and mildly elevated
      homocysteine concentrations, the elevated homocysteine concentration in
      atherosclerotic patients is also associated with most standard vascular risk
      factors, and importantly, with early decline in renal function, which is common
      in atherosclerosis. Decline in renal function alone causes elevated plasma
      homocysteine (and cysteine). These observations suggest that mild
      hyperhomocysteinemia could often be an effect rather than a cause of
      atherosclerotic disease. Data on the common C677T methylenetetrahydrofolate
      reductase polymorphism supports this, in that, although homozygosity is a
      frequent cause of mild hyperhomocysteinemia when plasma folate is below median
      population concentrations, it appears not to increase cardiovascular risk.
      Indeed, there is recent evidence suggesting an acute antioxidant effect of folic
      acid independent of its effect on homocysteine concentrations. This antioxidant
      mechanism may oppose an oxidant effect of homocysteine and be relevant to
      treatment of patients with vascular disease, especially those with chronic renal
      insufficiency. Such patients have moderately elevated plasma homocysteine and
      greatly increased cardiovascular risk that is largely unexplained.

PMID- 10919921
TI  - The controversy over homocysteine and cardiovascular risk.
AB  - Elevated plasma total homocysteine (tHcy) is a risk factor for occlusive
      cardiovascular disease (CVD). This concept is based on the observations of
      premature vascular disease in patients with homocystinuria, the relation between
      tHcy and both clinical CVD as well as preclinical atherosclerotic disease, the
      relation between tHcy in children and CVD in their parents or relatives, and
      reduction in CVD or surrogate endpoints after tHcy-lowering intervention with B
      vitamins. Plausible mechanisms include the in vivo interference with nitric oxide
      dependent reactive vasodilatation. Some observations have raised questions about
      tHcy as a risk factor. 1) Some prospective studies showed a weak relation or no
      relation between tHcy and CVD. 2) Several traditional risk factors are associated
      with tHcy and may confound the relation between tHcy and CVD. 3) tHcy is related
      to renal function, and hyperhomocysteinemia may reflect early nephrosclerosis. 4)
      The C677T transition of the methylenetetrahydrofolate reductase gene causes a
      moderate increase in tHcy but no or only minor increased CVD risk. However, the
      strength of some of these arguments can be questioned because there is increasing
      evidence that tHcy is a proximate risk factor provoking the acute event, it
      strongly interacts with traditional risk factors, and it may predict CVD or death
      in patients with chronic renal failure. Furthermore, the studies of the C677T
      polymorphism lack statistical power, and the TT genotype may even modulate CVD
      risk independently of homocysteine. Thus, only placebo-controlled intervention
      studies with tHcy-lowering B vitamins and clinical endpoints can provide
      additional valid arguments for the debate over whether tHcy is a causal CVD risk
      factor.

PMID- 10919922
TI  - Homocysteine and cardiovascular risk.

PMID- 10919923
TI  - Birth weight, socioeconomic class, and adult adiposity among African Americans.

PMID- 10919924
TI  - Antioxidants and stroke.

PMID- 10919925
TI  - Inflammation and Native American medicine: the role of botanicals.
AB  - There is a growing interest in medicinal botanicals as part of complementary
      medicine in the United States. In particular, both physicians and consumers are
      becoming aware of the use of herbals by Native American societies; many
      botanicals sold today as dietary supplements in the United States were used by
      Native Americans for similar purposes. Yet, these supplements represent only a
      small number of the >2500 different plant species from vascular taxa, and >2800
      species from all taxa, known to have been prized for their medicinal properties
      by the indigenous inhabitants of the North American continent. We review some of
      the studies of the immunomodulatory activities of botanicals used by native
      peoples of North America, the bioactive constituents responsible for those
      activities, and the mechanisms by which these constituents might modulate the
      immune system. We focus particularly on 3 species of purple coneflower
      (ECHINACEA:) because of the widespread use of purple coneflower in the United
      States to boost immunity and prevent upper respiratory infections. Seven of the
      10 most common botanicals sold in the United States were used extensively by
      Native Americans. However, there are very few data to support such use and even
      less information about drug toxicity or interactions.

PMID- 10919926
TI  - Estimating body fat in African American and white adolescent girls: a comparison
      of skinfold-thickness equations with a 4-compartment criterion model.
AB  - BACKGROUND: Although skinfold-thickness equations are widely used to estimate
      body fat, their accuracy in a biracial population of female adolescents has not
      been established. OBJECTIVE: We undertook this study to determine the agreement
      between 8 widely used skinfold-thickness equations and a 4-compartment criterion
      model in predicting the percentage body fat of 72 white and 40 African American
      girls aged 13.0 +/- 1.9 y. DESIGN: The biceps, triceps, suprailiac, subscapular,
      thigh, calf, and abdominal skinfold thicknesses of the subjects were measured
      with skinfold calipers and the buttocks circumference with a metal tape. The
      percentage fat mass (%FM) predicted by using each skinfold-thickness equation was
      compared with the criterion value calculated by the 4-compartment model on the
      basis of measurements of body density, body water, and bone mineral content.
      RESULTS: When the racial groups were analyzed separately, the Bland-Altman
      analysis indicated that the quadratic equations agreed most closely with the 4
      compartment model's measurement of %FM. Agreement of the other equations varied
      with body fatness. CONCLUSIONS: The quadratic equation of Slaughter et al is
      recommended for population studies in female adolescents because of its accuracy
      and simplicity. However, an individual %FM can be over- or underestimated by
      approximately 10% when this skinfold-thickness equation is used.

PMID- 10919927
TI  - A paradoxical increase in resting energy expenditure in malnourished patients
      near death: the king penguin syndrome.
AB  - BACKGROUND: The metabolic expression of extreme starvation on the verge of death
      is unknown in humans. OBJECTIVE: The objective was to compare the resting energy
      expenditure (REE) of 5 extremely malnourished dying patients [body mass index (in
      kg/m(2)): 9.77 +/- 0.1] with that of 16 less-malnourished anorexia nervosa (AN)
      patients. DESIGN: REE was measured by indirect calorimetry and body composition
      was measured by anthropometry and dual-frequency bioelectrical impedance
      analysis. Fasting serum insulin, thyroid hormone, and catecholamine
      concentrations were also determined. RESULTS: At the start of refeeding, REE was
      high in each of the 5 extremely malnourished dying patients, whereas it was low
      in the 16 AN patients (mean +/- SD: 5174 +/- 391 kJ/d compared with 3844 +/- 619
      kJ/d; P < 0.05). The high REE value in the 5 extremely malnourished dying
      patients was associated with almost no fat mass (FM), high urinary nitrogen loss
      (16.4 +/- 2.9 g/d), low serum fatty acid concentrations (0.36 +/- 0.23 mmol/L),
      and low or normal serum insulin, thyroid hormone, and catecholamine
      concentrations. During the first 2-4 wk of refeeding, REE and nitrogen loss
      decreased, whereas fatty acid concentrations increased in each of the 4 surviving
      patients; REE and urinary nitrogen output increased in the 16 AN patients.
      CONCLUSION: In malnourished persons near death, there is an increase in REE and
      in protein catabolism. The reason for this increase is unknown but could relate
      to consumption of the last mobilizable muscle mass and to diseased cellular
      membranes.

PMID- 10919928
TI  - Increasing the volume of a food by incorporating air affects satiety in men.
AB  - BACKGROUND: Previous research indicated that increasing the volume of food by
      adding water can lead to reductions in energy intake. However, the addition of
      water affects not only the volume but also the energy density (kJ/g) of foods. No
      studies have examined the effect of volume independent of energy density on
      intake. OBJECTIVE: We examined the effect of food volume independent of energy
      density on satiety. DESIGN: In a within-subjects design, 28 lean men consumed
      breakfast, lunch, and dinner in the laboratory 1 d/wk for 4 wk. On 3 d,
      participants received a preload 30 min before lunch and on 1 d no preload was
      served. Preloads consisted of isoenergetic (2088 kJ), yogurt-based milk shakes
      that varied in volume (300, 450, and 600 mL) as a result of the incorporation of
      different amounts of air. Preloads contained identical ingredients and weighed
      the same. RESULTS: The volume of the milk shake significantly affected energy
      intake at lunch (P < 0.04) such that intake was 12% lower after the 600-mL
      preload (2966 +/- 247 kJ) than after the 300-mL preload (3368 +/- 197 kJ).
      Subjects also reported greater reductions in hunger and greater increases in
      fullness after consumption of both the 450- and 600-mL preloads than after the
      300-mL preload. CONCLUSIONS: Changing the volume of a preload by incorporating
      air affected energy intake. Thus, the volume of a preload independent of its
      energy density can influence satiety.

PMID- 10919929
TI  - Macronutrient disposal during controlled overfeeding with glucose, fructose,
      sucrose, or fat in lean and obese women.
AB  - BACKGROUND: Previous short-term studies (< or =6 h) showed differences in energy
      expenditure (EE) and macronutrient oxidation in response to overfeeding with
      different types of dietary carbohydrate. This finding could have implications for
      obesity. OBJECTIVE: We used 96-h continuous whole-body calorimetry in 8 lean and
      5 obese women to assess metabolic disposal (energy dissipation and glycogen or
      fat storage) of a controlled excess of dietary energy supplied as different
      carbohydrate sources or as fat. DESIGN: Five dietary treatments were applied in
      random order: energy balance (control) and overfeeding by 50% of energy
      requirements with fat (O(fat)) or predominantly with glucose, fructose, or
      sucrose (O(cho)). Macronutrient oxidation rates were assessed from nonprotein
      gaseous exchanges. Net macronutrient balances were calculated as cumulative
      differences between intake and oxidation. RESULTS: Increased EE in response to
      overfeeding dissipated 7.9% of the energy excess with a variation in EE of <1.7%
      across overfeeding treatments (NS). EE during the O(fat) treatment significantly
      exceeded that during the control treatment in the lean but not in the obese
      women. There were no significant differences between lean and obese women in
      macronutrient oxidation or balances, so data were pooled. O(cho) induced glycogen
      storage on day 1 ( approximately 100 g) but thereafter progressively stimulated
      carbohydrate oxidation so that balance was reached on days 3 and 4. Fat oxidation
      was proportionately suppressed. Of the excess carbohydrate, 74% was oxidized;
      there were no significant differences between the various O(cho) treatments.
      O(fat) stimulated fat oxidation by 18% and suppressed carbohydrate oxidation. On
      average, 12% of the excess energy was stored as glycogen and 88% as fat; there
      was no significant difference between overfeeding treatments. CONCLUSION: There
      was no significant difference in fat balance during controlled overfeeding with
      fat, fructose, glucose, or sucrose.

PMID- 10919930
TI  - Early risk factors for increased adiposity: a cohort study of African American
      subjects followed from birth to young adulthood.
AB  - BACKGROUND: Obesity is an increasing concern in the United States. Effective
      prevention of obesity requires the risk factors to be well defined. African
      Americans have a high risk of obesity. OBJECTIVE: The objective of this study was
      to identify risk factors, present at birth, for increased adiposity in adulthood
      in an African American population. DESIGN: In this retrospective analysis of a
      prospective cohort study, anthropometric and socioeconomic variables were
      collected at birth. A representative sample of 447 African American subjects was
      followed up until young adulthood, when skinfold thickness was measured.
      Associations between the independent variables and increased adiposity (skinfold
      thickness above the 85th percentile) were explored by using unadjusted and
      adjusted analyses. RESULTS: Three variables measured at birth were independently
      associated with adiposity in young adulthood, explaining 12% of the variance. The
      odds ratios (with 95% CIs) of these variables for increased adiposity were 2.7
      (1.2, 6.2) for female sex, 4.0 (1.4, 11. 2) for first-born status, and 1.15
      (1.06, 1.25) for each unit increment in maternal prepregnancy body mass index
      (BMI; in kg/m(2)). After adjustment for these variables, birth weight for
      gestational age and socioeconomic variables were not associated with adiposity.
      CONCLUSIONS: This cohort study of African American subjects was the first to
      identify first-born status as an independent risk factor for increased adiposity
      in adulthood in a US population. The results of the study strengthen previous
      reports of the effect of female sex and maternal BMI on adulthood obesity.
      Identification of risk factors early in life may help target prevention toward
      high-risk children and allow healthy lifestyles to be established before the
      onset of obesity.

PMID- 10919931
TI  - Differences in associations of familial and nutritional factors with serum lipids
      between boys and girls: the Luxembourg Child Study.
AB  - BACKGROUND: Sex differences in the effects of genetic and environmental factors
      on circulating lipids have been examined mainly in adults, in whom the influences
      of sex steroid hormones are well known. OBJECTIVE: Our objective was to determine
      the effect of sex on genetic and environmental influences on serum lipids in
      prepubertal boys and girls. DESIGN: Children aged 6-8, 8-10, and 10-12 y (n =
      1028) were selected at random in the Belgian province of Luxembourg, a region in
      Europe with a high prevalence of risk factors for cardiovascular disease and
      diabetes. Blood glucose and serum cholesterol, triacylglycerol, and insulin
      concentrations were measured, and anthropometric data and blood pressure were
      recorded. Familial data were obtained from standardized questionnaires.
      Nutritional status was obtained from a 3-d record. Participation was 70.3% of the
      primary cohort. RESULTS: Cholesterol, triacylglycerol, and insulin values were
      among the highest recorded in studies of children. In girls, cholesterol
      correlated positively with the energy density of intake of saturated fat (r =
      0.13, P = 0.001), cholesterol (r = 0.11, P = 0.006), and protein (r = 0.12, P =
      0.007) and negatively with the ratio of polyunsaturated to saturated fat intake
      (r = -0.14, P = 0.001) and the energy density of carbohydrate intake (r = -0.11,
      P = 0.019). In boys, no such relations were found. Triacylglycerol was not
      significantly related to nutritional factors. Consistent, independent relations
      were found between reported elevated cholesterol concentrations in the parental
      and grandparental generation and cholesterol (r = 0.101, P = 0.011) and
      triacylglycerol (r = 0.09, P = 0.03) in boys. No such associations were found in
      girls. CONCLUSION: Environmental and genetic factors may have different effects
      on serum cholesterol in girls and boys.

PMID- 10919933
TI  - Isoflavone phytoestrogens consumed in soy decrease F(2)-isoprostane
      concentrations and increase resistance of low-density lipoprotein to oxidation in
      humans.
AB  - BACKGROUND: Oxidative damage to lipids may be involved in the etiology of
      atherosclerosis, cardiovascular disease in general, and cancer. The soy
      isoflavone phytoestrogens, genistein and daidzein, and equol (a daidzein
      metabolite produced by intestinal microflora) are antioxidants in vitro; equol is
      a particularly good inhibitor of LDL oxidation and membrane lipid peroxidation.
      OBJECTIVE: We sought to investigate the effects of a diet enriched with soy
      containing isoflavones on in vivo biomarkers of lipid peroxidation and resistance
      of LDL to oxidation, compared with a diet enriched with soy from which the
      isoflavones had been extracted. DESIGN: : A randomized, crossover design was used
      to compare diets enriched with soy that was low or high in isoflavones in 24
      subjects. Plasma concentrations of an F(2)-isoprostane, 8-epi-prostaglandin
      F(2)(alpha) (8-epi-PGF(2)(alpha)), a biomarker of in vivo lipid peroxidation, and
      resistance of LDL to copper-ion-induced oxidation were determined. RESULTS:
      Plasma concentrations of 8-epi-PGF(2)(alpha) were significantly lower after the
      high-isoflavone dietary treatment than after the low-isoflavone dietary treatment
      (326 +/- 32 and 405 +/- 50 ng/L, respectively; P = 0.028) and the lag time for
      copper-ion-induced LDL oxidation was longer (48 +/- 2.4 and 44 +/- 1.9 min,
      respectively; P = 0.017). Lag time for oxidation of unfractionated plasma and
      plasma concentrations of malondialdehyde, LDL alpha-tocopherol, polyunsaturated
      fatty acids, and isoflavonoids did not differ significantly between dietary
      treatments. CONCLUSIONS: Consumption of soy containing naturally occurring
      amounts of isoflavone phytoestrogens reduced lipid peroxidation in vivo and
      increased the resistance of LDL to oxidation. This antioxidant action may be
      significant with regard to risk of atherosclerosis, cardiovascular disease in
      general, and cancer.

PMID- 10919932
TI  - Effect of a fish-oil concentrate on serum lipids in postmenopausal women
      receiving and not receiving hormone replacement therapy in a placebo-controlled,
      double-blind trial.
AB  - BACKGROUND: n-3 Fatty acid supplementation lowered serum triacylglycerol
      concentrations in studies in which most of the subjects were male. The effects of
      n-3 fatty acid supplementation in postmenopausal women receiving and not
      receiving hormone replacement therapy (HRT) have received little attention.
      OBJECTIVE: We sought to determine the effects of a fish-oil-derived n-3 fatty
      acid concentrate on serum lipid and lipoprotein risk factors for cardiovascular
      disease in postmenopausal women receiving and not receiving HRT, with an emphasis
      on serum triacylglycerol concentrations and the ratio of triacylglycerol to HDL
      cholesterol. DESIGN: Postmenopausal women (n = 36) were grouped according to
      exogenous hormone use and were randomly allocated to receive 8 capsules/d of
      either placebo oil (control) or n-3 fatty acid-enriched oil (supplement). The
      supplement provided 2.4 g eicosapentaenoic acid (EPA) plus 1.6 g docosahexaenoic
      acid (DHA) daily. Serum lipids and the fatty acid composition of serum
      phospholipids were determined on days 0 and 28. RESULTS: Supplementation with n-3
      fatty acids was associated with 26% lower serum triacylglycerol concentrations (P
      < 0.0001), a 28% lower overall ratio of serum triacylglycerol to HDL cholesterol
      (P < 0.01), and markedly greater EPA and DHA concentrations in serum
      phospholipids (P < 0.05). CONCLUSIONS: These results show that supplementation
      with a fish-oil-derived concentrate can favorably influence selected
      cardiovascular disease risk factors, particularly by achieving marked reductions
      in serum triacylglycerol concentrations and triacylglycerol:HDL cholesterol in
      postmenopausal women receiving and not receiving HRT. This approach could
      potentially reduce the risk of coronary heart disease by 27% in postmenopausal
      women.

PMID- 10919934
TI  - Comparison of methods for assessing body-composition changes over 1 y in
      postmenopausal women.
AB  - BACKGROUND: Advances in dual-energy X-ray absorptiometry (DXA) software
      algorithms have improved the accuracy of this method for body-composition
      measurement. OBJECTIVE: Our objective was to compare the utility of DXA,
      underwater weighing (UWW), and a multicomponent model (MC) for assessing changes
      in body composition. DESIGN: : Previously sedentary women aged 40-66 y were
      randomly assigned to exercise training (ET; n = 36) and no exercise training (NT;
      n = 40). ET subjects exercised 3 d/wk; NT subjects remained sedentary. Changes in
      body mass, fat mass, and fat-free mass over 1 y were assessed by the 3 methods.
      RESULTS: Correlations among methods were significant and large (0.73-0.97). Body
      weight did not change significantly in either group. In the ET group, fat-free
      mass increased significantly as assessed by DXA (0.7 +/- 1.0 kg) but changes
      assessed by MC and UWW were not significant. Changes in fat mass and percentage
      body fat in the ET group were not significant. SDs for changes in fat mass and
      percentage body fat, respectively, from DXA were 2.5 kg and 2.7%; for MC, 5.5 kg
      and 7.1%; and for UWW, 4.4 kg and 5.8%. In the NT group, changes in fat-free
      mass, fat mass, and percentage body fat were significant (P </= 0.02) as assessed
      by MC (fat-free mass, -1.5 +/- 3.7 kg; fat mass, 2.3 +/- 4.1 kg; percentage body
      fat, 2.8 +/- 4.7%) and UWW (fat-free mass, -1.1 +/- 2.5 kg; fat mass, 2.1 +/- 3.6
      kg; percentage body fat, 2.5 +/- 3.5%), but changes by DXA were not significant
      (fat-free mass, 0.2 +/- 1.2 kg; fat mass, 1.0 +/- 3.9 kg; percentage body fat,
      0.6 +/- 3.2%). CONCLUSION: DXA was the most sensitive method for assessing small
      changes in body composition of postmenopausal women.

PMID- 10919935
TI  - Prospective evaluation of growth, nutritional status, and body composition in
      children with cystic fibrosis.
AB  - BACKGROUND: Several cross-sectional studies have shown improvement in the growth
      of children with cystic fibrosis (CF) because of increased awareness of and more
      comprehensive care of their special nutritional needs. However, longitudinal data
      on the nutritional status of these children are rare. OBJECTIVE: The objective
      was to compare changes in growth, body composition, and nutritional status
      between children with and without CF. DESIGN: This was a prospective 3-y cohort
      study of 25 children aged 5-10 y with CF, mild pulmonary disease, and pancreatic
      insufficiency and of 26 healthy control children. Three methods were used to
      assess body composition: measurements of skinfold thickness, total body water by
      deuterium oxide, and total-body electrical conductivity. Growth and body
      composition changes over time were analyzed by a longitudinal mixed-effects
      model. RESULTS: Over the 3 y of the study, the statural growth of the boys with
      CF was slower than that of the control subjects (P = 0.004). The same divergence
      over time between the boys with and without CF was observed for fat-free mass
      assessed by skinfold-thickness measurements and total body water (P = 0.008 and
      0.02, respectively) and for fat mass assessed by skinfold-thickness measurements
      and total-body electrical conductivity (P = 0.009 and 0.001, respectively). The
      differences in the pattern of changes in growth and body composition were less
      striking for girls. CONCLUSIONS: Despite comprehensive care, the growth of boys
      with CF was impaired on the basis of height, fat-free mass, and fat mass, when
      observed longitudinally. Caution should be used when interpreting cross-sectional
      measurements because they often do not detect suboptimal growth.

PMID- 10919936
TI  - Effects of a salt-restricted diet on the intake of other nutrients.
AB  - BACKGROUND: Salt restriction, recommended as the first-line treatment of
      hypertension, has been proposed to lead to deficiencies in intakes of some other
      nutrients. OBJECTIVE: The aim of this study was to investigate the effects of
      salt restriction for 20 wk on the intake of other nutrients in free-living
      subjects with mildly elevated blood pressure. DESIGN: Thirty-nine subjects (24
      men, 15 women) aged 28-65 y with a mean daytime ambulatory diastolic blood
      pressure of 90-105 mm Hg and a diastolic blood pressure measured in a health care
      center of 95-115 mm Hg participated in the study. The subjects completed 4-d food
      records and their salt intake was measured by 24-h urinary sodium excretion. The
      subjects received both oral and written instructions from a clinical nutritionist
      on how to reduce their daily sodium chloride intake to <5 g/d but were instructed
      not to change their diet otherwise. The subjects were provided with low-salt
      bread during the salt-restriction period. RESULTS: Few changes were found in
      nutrient intakes. In men, total energy intake decreased by 1059 kJ/d and alcohol,
      potassium, and vitamin D intakes decreased, but there were no significant changes
      in energy-adjusted potassium and vitamin D intakes. In women, total potassium
      intake increased, but the potassium density of the diet remained unchanged. Total
      selenium intake and energy-adjusted intake of selenium both decreased
      significantly in women. CONCLUSIONS: Salt restriction can be undertaken in free
      living hypertensive subjects without any untoward changes in the intake of other
      nutrients.

PMID- 10919937
TI  - An endocrine and metabolic definition of the intermeal interval in humans:
      evidence for a role of leptin on the prandial pattern through fatty acid
      disposal.
AB  - BACKGROUND: It has been proposed that leptin provides a hormonal link between
      adipose stores and food intake. OBJECTIVE: This study investigated the role of
      leptin in the prandial pattern. DESIGN: In experiment 1, a spontaneous prandial
      pattern was recreated in 6 young, normal-weight men who were deprived of time
      cues and had blood withdrawn continuously at a frequency of one tube every 5 min.
      Meals were consumed ad libitum and dinner was requested voluntarily. Data from a
      second experiment, conducted in 8 subjects, were used to confirm the changes in
      leptin during the intermeal interval (IMI). RESULTS: Plasma leptin gradually rose
      to a peak (62 +/- 18% of the lunch concentration) during the IMI and declined
      before the dinner request (-21 +/- 4% of the peak concentration). This
      preprandial decline was confirmed in experiment 2 (-15 +/- 9%). The leptin
      concentration at lunch and fat-free mass were the only significant predictors of
      the IMI (both: r(2) = 0.91, P = 0.03). With fat intake at lunch, the leptin
      concentration at lunch was a positive predictor of the area under the curve of
      plasma fatty acids during the IMI (r(2) = 0.95, P = 0.01). Moreover, the leptin
      concentration at lunch was negatively correlated with energy intake in the first
      course of this meal (r = -0.95, P < 0.005). A similar result was found at dinner
      (r = -0.85, P < 0.05). Last, the change in leptin was predicted accurately by
      changes in glucose, triacylglycerol, and fatty acids (r(2) = 0.87, P < 10(-5)).
      CONCLUSION: Plasma leptin concentrations increase during a spontaneous IMI and
      decline before the onset of a meal. The results argue for a role of leptin in the
      prandial pattern through fatty acid peripheral disposal.

PMID- 10919938
TI  - Digestion of so-called resistant starch sources in the human small intestine.
AB  - BACKGROUND: Resistant starch sources, which are only partially digested in the
      small intestine, can be used to increase colonic availability of short-chain
      fatty acids. OBJECTIVE: To study the characteristics of the fermentation of
      resistant starch, the digestion of resistant starch in the small intestine has to
      be quantified. We compared the metabolic fates of highly digestible cornstarch
      (DCS), Hylon VII (type 2 resistant starch), and Novelose 330 (type 3 resistant
      starch), which are of corn origin and, therefore, naturally enriched in (13)C.
      DESIGN: After administration of 40 g starch or glucose to 7 healthy volunteers,
      glucose and exogenous glucose concentrations in serum and (13)CO(2) excretion in
      breath were analyzed for 6 h. (13)C abundance in carbon dioxide was analyzed by
      isotope ratio mass spectrometry (IRMS) and (13)C abundance in glucose by gas
      chromatography-combustion IRMS. RESULTS: By comparing the area under the curve (2
      h) of exogenous glucose concentration in serum ((13)C glycemic index) after
      intake of starch or glucose, (13)C glycemic indexes for DCS, Hylon VII, and
      Novelose 330 were calculated to be 82 +/- 23%, 44 +/- 16%, and 43 +/- 15%,
      respectively. Comparison of 6-h cumulative percentage dose recovery in breath
      showed that 119 +/- 28% of DCS, 55 +/- 23% of Hylon VII, and 50 +/- 26% of
      Novelose 330 was digested in the small intestine. CONCLUSION: The exogenous
      glucose response in serum and the (13)CO(2) excretion in breath can be used to
      estimate small intestinal digestion of resistant starch, which amounts to
      approximately 50%.

PMID- 10919939
TI  - Comparison of high- and low-glycemic-index breakfast cereals with monounsaturated
      fat in the long-term dietary management of type 2 diabetes.
AB  - BACKGROUND: Results of 6-wk studies suggest that high-carbohydrate diets are
      deleterious for people with type 2 diabetes. OBJECTIVE: Our objective was to see
      whether long-term replacement of dietary monounsaturated fatty acids (MUFAs) with
      carbohydrate from breakfast cereals with either a high or a low glycemic index
      (GI) affected blood glucose and lipids in subjects with type 2 diabetes. DESIGN:
      Subjects with type 2 diabetes (n = 91) were randomly assigned to receive
      approximately 10% of energy from a low-GI breakfast cereal, a high-GI cereal, or
      oil or margarine containing MUFA for 6 mo. Eating breakfast cereal was prohibited
      for subjects in the MUFA group. RESULTS: Seventy-two subjects completed the
      trial. The subjects who received cereals consumed approximately 10% more energy
      from carbohydrate than did the subjects in the MUFA group. Changes in glycated
      hemoglobin, body weight, and fasting cholesterol and triacylglycerol did not
      differ significantly among groups. HDL cholesterol increased by approximately 10%
      in the MUFA group compared with subjects who consumed either high- or low-GI
      cereals (P = 0.002). The ratio of total to HDL cholesterol was higher in the
      subjects who consumed the high-GI cereal than in the MUFA group at 3 mo but not
      at 6 mo (diet x time interaction, P = 0.041). During 8-h metabolic profiles, mean
      plasma insulin was higher and mean free fatty acids were lower in the 2 cereal
      groups than in the MUFA group (P < 0.05). CONCLUSIONS: A 10% increase in
      carbohydrate intake associated with breakfast cereal consumption had no
      deleterious effects on glycemic control or blood lipids over 6 mo in subjects
      with type 2 diabetes. The increase in plasma insulin and the reduction in free
      fatty acids associated with higher carbohydrate intake may reduce the rate of
      progression of diabetes.

PMID- 10919940
TI  - Retinol concentrations in capillary dried blood spots from healthy volunteers:
      method validation.
AB  - BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in the
      developing world, leading to >3 million eye-related problems in preschool
      children. Nearly 250 million children have subclinical VAD, resulting in a 23%
      increase in childhood mortality. Difficulties in obtaining samples to assess VAD
      have hampered the detection, intervention, and surveillance of VAD. The use of
      dried blood spots (DBS) could ameliorate many problems of vitamin A assessment.
      OBJECTIVE: The objective of this study was to validate the use of retinol in DBS
      for vitamin A assessment by comparing it with venous and capillary serum retinol.
      DESIGN: Venous and capillary blood specimens were obtained simultaneously from 20
      healthy adult volunteers. From each blood specimen, both DBS and liquid serum
      were prepared (a total of 80 samples). All specimens were maintained at -70
      degrees C until HPLC analysis. RESULTS: The mean retinol concentrations in the 4
      sample types were as follows: venous serum (2.02 +/- 0.42 micromol/L, or 58 +/-
      12 microg/dL), capillary serum (2.06 +/- 0.42 micromol/L, or 59 +/- 12
      microg/dL), venous DBS (2.06 +/- 0.49 micromol/L, or 59 +/- 14 microg/dL), and
      capillary DBS (2.09 +/- 0.45 micromol/L, or 60 +/- 13 microg/dL). Of the 6
      possible 2-way combinations, the R(2) values ranged from 0.77 for capillary DBS
      versus venous DBS to 0.95 for venous serum versus capillary serum. CONCLUSIONS:
      DBS retinol measured by HPLC is comparable with serum retinol. Thus, it is
      possible to compare and combine blood retinol concentration data obtained from
      DBS with current and historic measurements in serum.

PMID- 10919941
TI  - Bioconversion of plant carotenoids to vitamin A in Filipino school-aged children
      varies inversely with vitamin A status.
AB  - BACKGROUND: It is important to understand the factors affecting strategies to
      improve the vitamin A status of populations. We reported previously that a 3-d
      deuterated-retinol-dilution (DRD) procedure might be used to indicate total body
      stores of vitamin A. OBJECTIVE: We studied the ability of 3-d DRD to detect
      changes in the body pool size of vitamin A and the effect of vitamin A status on
      the bioconversion of plant carotenoids to vitamin A. DESIGN: Two separate,
      unrelated studies were conducted in 7-13-y-old children with poor or marginal
      serum retinol concentrations (0.32-0.93 micromol/L) by feeding them controlled
      diets daily for 5 d/wk for 12 wk, after treatment with an anthelmintic drug. In
      school 1 (n = 27), lunch and 2 snacks that were provided at school contained 2258
      retinol equivalents/d (mostly from orange fruit and vegetables) and 5.3 MJ/d from
      33 g fat, 37 g protein, and 209 g carbohydrates; in school 2 (n = 25), 2 snacks
      provided 2.5 MJ/d from 9.4 g fat, 9.6 g protein, and 119 g carbohydrates, but no
      carotenes. RESULTS: In school 1, mean serum beta-carotene increased from 0.12 to
      0.62 micromol/L (P = 0.0001) and serum retinol increased from 0.68 to 1. 06
      micromol/L (P = 0.0001). In school 2, serum beta-carotene increased from 0.06 to
      0.11 micromol/L (P = 0.0001) and serum retinol increased from 0.66 to 0.86
      micromol/L (P = 0.0001). In school 1, but not school 2, improvement in serum
      retinol varied inversely with baseline retinol (r = -0.38, P = 0.048). In both
      schools, 3-d DRD showed reductions in the ratio of serum deuterated to
      nondeuterated retinol (D:H retinol) postintervention, denoting improvements in
      vitamin A status; the higher D:H retinol (ie, the poorer the status) at baseline,
      the greater the reduction in D:H retinol postintervention (school 1: r = -0.99, P
      = 0.0001; school 2: r = -0.89, P = 0.0001). CONCLUSIONS: Three-day DRD can detect
      changes in the body pool size of vitamin A, although a predictive equation to
      quantitate total body stores of vitamin A with the use of 3-d data needs to be
      developed. Bioconversion of plant carotenoids to vitamin A varies inversely with
      vitamin A status; improvement in status after dietary interventions is strongly
      influenced by total body stores of vitamin A and is influenced little or not at
      all by serum retinol.

PMID- 10919942
TI  - Factors associated with calcium absorption efficiency in pre- and perimenopausal
      women.
AB  - BACKGROUND: The amount of calcium ingested by an individual may affect several
      chronic conditions, including osteoporosis, hypertension, and colon cancer.
      However, individuals vary in their ability to absorb the calcium they consume.
      OBJECTIVE: The purpose of this study was to examine sources of interindividual
      variation in the efficiency of calcium absorption in women. DESIGN: Fractional
      calcium absorption was estimated in 142 healthy pre- and perimenopausal women.
      Dietary habits, lifestyle factors, calciotropic hormones, and vitamin D receptor
      gene polymorphisms were also assessed. RESULTS: Calcium absorption values
      averaged 35% and ranged from 17% to 58%. Fractional calcium absorption was
      positively associated with body mass index (r = 0.22, P = 0.007), dietary fat
      intake (r = 0.29, P = 0.001), serum 1,25 dihydroxyvitamin D [1,25(OH)(2)D]
      concentrations (r = 0.23, P = 0. 006), and parathyroid hormone concentrations (r
      = 0.21, P = 0.015). Fractional calcium absorption was inversely associated with
      total calcium intake (r = -0.18, P = 0.030), dietary fiber intake (r = -0. 19, P
      = 0.028), alcohol consumption (r = -0.14, P = 0.094), physical activity (r = 
      0.22, P = 0.007), and symptoms of constipation (r = -0.16, P = 0.059). In
      stepwise regression analysis, dietary fat, dietary fiber, serum 1,25(OH)(2)D, and
      alcohol consumption emerged as independent predictors of calcium absorption,
      explaining 21.02% of the observed variation. Women in the lowest tertile of the
      ratio of dietary fat to fiber had 19% lower fractional calcium absorption values
      than did women in the highest tertile of ratio of dietary fat to fiber (test of
      trend, P < 0.001). CONCLUSIONS: There is a wide range of calcium absorption
      values in healthy women. The amount of dietary fat consumed relative to dietary
      fiber appears to have an important role in determining differences in calcium
      absorption performance among individuals.

PMID- 10919943
TI  - Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy
      subjects in Delhi.
AB  - BACKGROUND: Despite abundant sunlight, rickets and osteomalacia are prevalent in
      South Asian countries. The cause of this paradox is not clear. OBJECTIVE: The
      objective was to assess 25-hydroxyvitamin D [25(OH)D] status and its functional
      significance in apparently healthy subjects residing in Delhi, a city in the
      northern part of India. DESIGN: Serum 25(OH)D, total calcium, inorganic
      phosphate, alkaline phosphatase, intact parathyroid hormone, and 1, 25
      dihydroxyvitamin D [1,25(OH)(2)D] were measured in groups of healthy subjects who
      differed with respect to variables relevant to vitamin D and bone mineral
      metabolic status, such as direct sunlight exposure, season of measurement, skin
      pigmentation, dietary calcium and phytate contents, and altered physiologic
      states such as pregnancy and neonatal age. RESULTS: All groups except one with
      maximum direct sunlight exposure had subnormal concentrations of 25(OH)D. The
      25(OH)D-deficient groups tended to have an imbalance in bone mineral metabolic
      homeostasis when exposed to winter weather and low dietary calcium and high
      dietary phytate, with significantly low calcium and elevated intact parathyroid
      hormone concentrations, chemical osteomalacia, or both. Increased values of
      1,25(OH)(2)D during pregnancy did not help correct the imbalance in bone mineral
      metabolic homeostasis. CONCLUSION: Healthy subjects with low 25(OH)D
      concentrations are at risk of bone mineral metabolic imbalance when exposed to
      factors that strain bone mineral homeostasis.

PMID- 10919944
TI  - Intake of antioxidant vitamins and risk of death from stroke in postmenopausal
      women.
AB  - BACKGROUND: Antioxidant vitamins may play a role in the prevention of stroke
      because they scavenge free radicals and prevent LDL oxidation. Epidemiologic
      studies that have examined this relation produced conflicting results. OBJECTIVE:
      We examined the association between antioxidant vitamin intakes and death from
      stroke. DESIGN: This was a prospective cohort study of 34492 postmenopausal
      women. RESULTS: During follow-up, 215 deaths from stroke were documented. Total
      vitamin A, carotenoid, and vitamin E intakes were not associated with death from
      stroke after multivariate adjustment. Relative risks (RRs) and 95% CIs of the
      highest compared with the lowest category were 0.79 (0.45, 1.38; P for trend =
      0.33) for vitamin A, 0.80 (0.45, 1.40; P for trend = 0.40) for carotenoids, and
      0.91 (0.55, 1.52; P for trend = 0.86) for vitamin E. The test for trend for total
      vitamin C intake was significant, although the association appeared somewhat U
      shaped, not monotonic. An inverse association was seen between death from stroke
      and vitamin E intake from food. RRs (and 95% CIs) of death from stroke from the
      lowest to highest intake categories were 1.0, 0.80 (0.51, 1.26), 0.93 (0.58, 1.
      49), 0.67 (0.39, 1.14), 0.40 (0.20, 0.80); P for trend = 0.008. The results
      suggest inverse associations between death from stroke and intakes of the most
      concentrated vitamin E food sources consumed by this cohort: mayonnaise, nuts,
      and margarine. CONCLUSIONS: Our results suggest a protective effect of vitamin E
      from foods on death from stroke but do not support a protective role for
      supplemental vitamin E or other antioxidant vitamins. However, given the number
      of deaths from stroke in the present cohort, a small-to-moderate association
      could not be ruled out.

PMID- 10919945
TI  - Serum leptin concentrations in infants: effects of diet, sex, and adiposity.
AB  - BACKGROUND: Leptin, the product of the obese (ob) gene, is a regulator of food
      intake and energy metabolism. Immunoreactive leptin was detected recently in
      breast milk and it has been hypothesized that leptin may be absorbed and may
      contribute to differences in body composition between breast-fed and formula-fed
      infants. OBJECTIVE: The objective was to evaluate whether diet, adiposity, or sex
      affect plasma leptin in breast-fed and formula-fed infants. DESIGN: Venous blood
      samples were drawn from healthy, exclusively breast-fed or formula-fed Swedish
      infants at 1, 4, and 6 mo of age (n = 193) and from 12-mo-old Finnish infants (n
      = 79). Anthropometric measurements were made and plasma samples were analyzed for
      leptin, insulin, and glucose. RESULTS: There were no significant differences in
      plasma leptin between formula-fed and breast-fed infants at 1 and 4 mo of age,
      whereas formula-fed infants had significantly higher ( approximately 5%) leptin
      concentrations at 6 mo of age. Similar results were observed after correction for
      BMI. Plasma leptin was 15-25% higher in female than in male infants at 1, 4, and
      12 mo of age (P < 0.05), also after correction for BMI. When all infants were
      analyzed together, a positive correlation (r = 0.34, P < 0.0001) was found
      between plasma leptin and BMI. Very low leptin concentrations were found in
      breast milk after centrifugation and the high concentrations reported previously
      were likely due to interference in the assay by milk fat. CONCLUSIONS: Plasma
      leptin concentrations are not higher in breast-fed than in formula-fed infants;
      however, sex and adiposity affect leptin concentrations even at this early age.

PMID- 10919946
TI  - Evaluation of waist circumference, waist-to-hip ratio, and the conicity index as
      screening tools for high trunk fat mass, as measured by dual-energy X-ray
      absorptiometry, in children aged 3-19 y.
AB  - BACKGROUND: A central fat pattern has adverse health implications in both
      children and adults. Because adiposity tracks from childhood into adulthood, the
      ability of simple anthropometric techniques to correctly measure truncal
      adiposity in childhood needs to be assessed. OBJECTIVES: We sought to assess the
      validity of waist circumference, waist-to-hip ratio (WHR), and the conicity index
      as indicators of trunk fat mass in children and adolescents. DESIGN: Trunk fat
      mass (kg) was measured with dual-energy X-ray absorptiometry in 278 girls and 302
      boys aged 3-19 y. Receiver operating characteristic (ROC) curves and areas under
      the curves (AUCs) for the ROCs were calculated to compare the relative abilities
      of the anthropometric measures to correctly identify children with high trunk fat
      mass (z score for our study population of > or =1). RESULTS: The 80th percentile
      for waist circumference correctly identified 89% of girls and 87% of boys with
      high trunk fat mass (sensitivity) and 94% of girls and 92% of boys with low trunk
      fat mass (specificity). Waist circumference performed significantly better as an
      index of trunk fat mass than did WHR or the conicity index, as shown by the AUCs
      in girls and boys, respectively: waist circumference AUCs = 0.97 and 0.97,
      conicity index AUCs = 0.80 and 0.81, and WHR AUCs = 0.73 and 0.71. Our cutoffs
      for high trunk fat mass and high waist circumference are provided for both sexes
      for each year of age. CONCLUSION: Waist circumference provides a simple yet
      effective measure of truncal adiposity in children and adolescents.

PMID- 10919947
TI  - Phase angle from bioelectrical impedance analysis remains an independent
      predictive marker in HIV-infected patients in the era of highly active
      antiretroviral treatment.
AB  - BACKGROUND: Highly active antiretroviral treatment (HAART) reduces the risk of
      wasting in HIV infection and may alter the prognostic weight of wasting. The
      phase angle from bioelectrical impedance analysis (BIA) can be interpreted as a
      surrogate marker for the catabolic reaction to chronic HIV infection and
      opportunistic disease. OBJECTIVE: Our objective was to assess the prognostic
      ability of the phase angle in HIV-infected patients in the era of HAART. DESIGN:
      Two cross-sectional observation studies were conducted in 1996 and 1997 at a
      German university outpatient HIV clinic. In the 1996 and 1997 cohorts, HAART was
      prescribed to 17 of 212 and 168 of 257 patients at baseline and to 179 of 212 and
      234 of 257 patients during observation, respectively. Whole-body BIA was assessed
      at 50 KHz. Time to clinical progression and survival were calculated by using Cox
      proportional hazard models with time-dependent covariates. Median observation
      times were 1000 and 515 d for the 1996 and 1997 cohorts, respectively. RESULTS:
      Higher phase angle was associated with a lower relative mortality risk, adjusted
      for viral load and CD4(+) cell count, of 0.49 (95% CI: 0.30, 0.81) per degree in
      1996 and of 0.33 (95% CI: 0.18, 0.61) in 1997. The influence of phase angle on
      time to clinical progression, adjusted for viral load and CD4(+) cell count, was
      not significant in 1996 but the relative risk was 0.58 (0.36, 0.83) in 1997.
      CONCLUSION: Despite the favorable effects of HAART on the nutritional status of
      HIV-infected persons, low phase angle remains an independent adverse prognostic
      marker of clinical progression and survival.

PMID- 10919949
TI  - Is oleic acid or squalene the important preventive agent?

PMID- 10919950
TI  - Opening remarks

PMID- 10919951
TI  - Preface

PMID- 10919952
TI  - Is there a metabolic basis for dietary supplementation?
AB  - To be efficacious, dietary supplements must either provide a nutrient that is
      normally undersupplied to cells or exert a pharmacologic effect on cellular
      processes. In the first case, optimal function is achieved when a nutrient
      required by the organism reaches a specific concentration within the cell. A
      supplement has benefit only when the normal intake of a bioavailable form of a
      nutrient is lower than the amount that would provide maximum benefit as judged
      from all biological perspectives. Metabolic, environmental, and genetic factors
      can make individual nutrient requirements differ from the estimated needs
      calculated from population-based data. For example, under certain circumstances
      intracellular antioxidants may be depleted and a dietary supplement might restore
      optimal antioxidant protection. In the second case, the dietary supplement
      contains a constituent that is normally not required by the cell, but this
      substance is capable of altering normal cell function. For example, herbal
      preparations may contain ephedrine (a drug), which might alter heart rate so that
      the amount of blood pumped by the heart is enhanced. An understanding of how the
      variation in nutrient requirements comes about and of the pharmacologic actions
      of nutrient supplements can help to identify which individuals are most likely to
      benefit from dietary supplements.

PMID- 10919953
TI  - Physical activity as a metabolic stressor.
AB  - Both physical activity and diet stimulate processes that, over time, alter the
      morphologic composition and biochemical function of the body. Physical activity
      provides stimuli that promote very specific and varied adaptations according to
      the type, intensity, and duration of exercise performed. There is further
      interest in the extent to which diet or supplementation can enhance the positive
      stimuli. Prolonged walking at low intensity presents little metabolic, hormonal,
      or cardiovascular stress, and the greatest perturbation from rest appears to be
      from increased fat oxidation and plasma free fatty acid mobilization resulting
      from a combination of increased lipolysis and decreased reesterification. More
      intense jogging or running largely stimulates increased oxidation of glycogen and
      triacylglycerol, both of which are stored directly within the muscle fibers.
      Furthermore, these intramuscular stores of carbohydrate and fat appear to be the
      primary substrates for the enhanced oxidative and performance ability derived
      from endurance training-induced increases in muscle mitochondrial density.
      Weightlifting that produces fatigue in brief periods (ie, in 15-90 s and after 15
      repetitive contractions) elicits a high degree of motor unit recruitment and
      muscle fiber stimulation. This is a remarkably potent stimulus for altering
      protein synthesis in muscle and increasing neuromuscular function. The metabolic
      stress of physical activity can be measured by substrate turnover and depletion,
      cardiovascular response, hormonal perturbation, accumulation of metabolites, or
      even the extent to which the synthesis and degradation of specific proteins are
      altered, either acutely or by chronic exercise training.

PMID- 10919954
TI  - Growth and pubertal development in children and adolescents: effects of diet and
      physical activity.
AB  - The longitudinal growth of an individual child is a dynamic statement of the
      general health of that child. Measurements should be performed often and
      accurately to detect alterations from physiologic growth. Although any single
      point on the growth chart is not very informative, when several growth points are
      plotted over time, it should become apparent whether that individual's growth is
      average, a variant of the norm, or pathologic. Somatic growth and maturation are
      influenced by several factors that act independently or in concert to modify an
      individual's genetic growth potential. Linear growth within the first 2 y of life
      generally decelerates but then remains relatively constant throughout childhood
      until the onset of the pubertal growth spurt. Because of the wide variation among
      individuals in the timing of the pubertal growth spurt, there is a wide range of
      physiologic variations in normal growth. Nutritional status and heavy exercise
      training are only 2 of the major influences on the linear growth of children. In
      the United States, nutritional deficits result from self-induced restriction of
      energy intake. That single factor, added to the marked energy expenditure of
      training and competition for some sports, and in concert with the self-selection
      of certain body types, makes it difficult to identify the individual factors
      responsible for the slow linear growth of some adolescent athletes, for example,
      those who partake in gymnastics, dance, or wrestling.

PMID- 10919955
TI  - The aging process as a modifier of metabolism.
AB  - Because elderly adults have distinct metabolic characteristics that alter various
      nutrient requirements, simple extrapolations of nutrient requirements for younger
      adults are not warranted. Gastrointestinal function is well preserved with aging
      regarding the digestion and absorption of macronutrients, but the aging
      gastrointestinal tract becomes less efficient in absorbing vitamin B-12, vitamin
      D, and calcium. The new dietary reference intakes considered recent studies in
      aging adults and concluded that the recommended dietary allowances (RDAs) should
      be 1200 mg and 15 microg for calcium and vitamin D, respectively, for persons
      over the age of 70 y. The new RDAs for riboflavin, niacin, thiamine, folate,
      vitamin B-6, and vitamin B-12 are not different for persons in the oldest age
      category (>70 y) than for those aged 51-70 y. Because this is a quickly advancing
      field, it will be important to closely follow new research on nutrient
      requirements and aging over the next several years.

PMID- 10919956
TI  - Overnutrition and undernutrition as modifiers of metabolic processes in disease
      states.
AB  - Both overnutrition and undernutrition affect energy metabolism, with
      overnutrition raising energy expenditure and undernutrition lowering it. Fever is
      a powerful stimulator of thermogenesis. In diseases such as cancer, AIDS,
      diabetes mellitus, and rheumatoid arthritis, whether energy expenditure is
      increased or decreased often depends on how advanced the disorder is. Early on,
      when the greater protein turnover characteristic of these conditions is
      paramount, energy expenditure is increased. In addition, in diseases such as
      cancer, AIDS, and rheumatoid arthritis in which cytokines are released, the
      cytokines' thermogenic effect initially increases the metabolic rate. However, as
      the disease becomes more advanced and leads to cachexia, energy expenditure drops
      below normal. Acute conditions such as burns and trauma significantly raise
      energy expenditure, primarily by increasing sympathetic response and the release
      of catecholamines, which are powerful stimulators of energy expenditure.

PMID- 10919957
TI  - Supplements: questions to ask to reduce confusion.
AB  - Written and oral statements concerning supplements are delivered daily to
      audiences that span the full spectrum of demographics. Yet the common reaction of
      these audiences to these statements is that they are receiving mixed messages.
      One source of this confusion could be greatly reduced if each statement
      concerning supplements always defined the specific parameters of the studies on
      which the statement is based. Those receiving information about supplements must
      be made aware that extrapolation of data for one form of a supplement to predict
      the result of another form many be harmful to one's health. If a statement
      concerning a supplement does not clearly define the route of delivery, its
      matrix, the quantity of compound, the purity of compound, and the physiologic
      condition of the recipient, the statement should be disregarded by all audiences.
      If the creators of all types of supplement information define these parameters,
      and if audiences critically review the information provided, confusion concerning
      supplements will be reduced.

PMID- 10919958
TI  - Methodologic issues in measuring physical activity and physical fitness when
      evaluating the role of dietary supplements for physically active people.
AB  - Physical activity and physical fitness are complex entities comprising numerous
      diverse components that present a challenge in terms of accurate, reliable
      measurement. Physical activity can be classified by its mechanical (static or
      dynamic) or metabolic (aerobic or anaerobic) characteristics and its intensity
      (absolute or relative to the person's capacity). Habitual physical activity can
      be assessed by using a variety of questionnaires, diaries, or logs and by
      monitoring body movement or physiologic responses. Selection of a measurement
      method depends on the purpose of the evaluation, the nature of the study
      population, and the resources available. The various components of physical
      fitness can be assessed accurately in the laboratory and, in many cases, in the
      field by using a composite of performance tests. Most coaches and high-level
      athletes would accept as very beneficial a dietary supplement that would increase
      performance in a competitive event by even 3%; for example, lowering a runner's
      time of 3 min, 43 s in the 1500 m by 6.7 s. To establish that such small changes
      are caused by the dietary supplement requires carefully conducted research that
      involves randomized, placebo-controlled, double-blind studies designed to
      maximize statistical power. Statistical power can be increased by enlarging
      sample size, selecting tests with high reliability, selecting a potent but safe
      supplement, and maximizing adherence. Failure to design studies with adequate
      statistical power will produce results that are unreliable and will increase the
      likelihood that a true effect will be missed.

PMID- 10919959
TI  - Protein supplements and exercise.
AB  - Active persons ingest protein supplements primarily to promote muscle strength,
      function, and possibly size. Currently, it is not possible to form a consensus
      position regarding the benefit of protein or amino acid supplements in exercise
      training. Determination of whether supplements are beneficial has been hampered
      by the failure to select appropriate endpoints for evaluation of a positive
      effect. Furthermore, studies focused at a more basic level have failed to agree
      on the response of protein metabolism to exercise. An additional complication of
      dietary studies that is not often taken into account is amount of energy intake.
      Because of these and other complications, studies at the whole body level have
      not yielded a clear picture of the need for, or response to, dietary protein or
      amino acid supplements. Consequently, it is necessary to examine this issue at
      the tissue level. In untrained subjects, both muscle protein breakdown and
      synthesis are increased in response to exercise. Amino acid intake further
      stimulates muscle protein synthesis after exercise as a consequence of
      stimulating amino acid transport into the intramuscular compartment. The
      stimulatory effect of amino acids after exercise is greater than the effect of
      amino acids on muscle protein synthesis when given at rest. These data suggest
      that not only may the exact composition and amount of an amino acid supplement be
      important, but the timing of ingestion of the supplement in relation to the
      exercise must be considered in designing future studies to evaluate the efficacy
      of amino acid supplements.

PMID- 10919960
TI  - Lipid metabolism during endurance exercise.
AB  - Endogenous triacylglycerols represent an important source of fuel for endurance
      exercise. Triacylglycerol oxidation increases progressively during exercise; the
      specific rate is determined by energy requirements of working muscles, fatty acid
      delivery to muscle mitochondria, and the oxidation of other substrates. The
      catecholamine response to exercise increases lipolysis of adipose tissue
      triacylglycerols and, presumably, intramuscular triacylglycerols. In addition,
      increases in adipose tissue and muscle blood flow decrease fatty acid
      reesterification and facilitate the delivery of released fatty acids to skeletal
      muscle. Alterations in fatty acid mobilization and the relative use of adipose
      and intramuscular triacylglycerols during exercise depend, in large part, on
      degree of fitness and exercise intensity. Compared with untrained persons
      exercising at the same absolute intensity, persons who have undergone endurance
      training have greater fat oxidation during exercise without increased lipolysis.
      Available evidence suggests that the training-induced increase in fat oxidation
      is due primarily to increased oxidation of non-plasma-derived fatty acids,
      perhaps from intramuscular triacylglycerol stores. Fat oxidation is lower in high
      intensity exercise than in moderate-intensity exercise, in part because of
      decreased fatty acid delivery to exercising muscles. Parenteral lipid
      supplementation during high-intensity exercise increases fat oxidation, but the
      effect of ingesting long-chain or medium-chain triacylglycerols on substrate
      metabolism during exercise is less clear. This review discusses the relation
      between fatty acid mobilization and oxidation during exercise and the effect of
      endurance training, exercise intensity, and lipid supplementation on these
      responses.

PMID- 10919962
TI  - Serotonin and central nervous system fatigue: nutritional considerations.
AB  - Fatigue from voluntary muscular effort is a complex phenomenon involving the
      central nervous system (CNS) and muscle. An understanding of the mechanisms
      within muscle that cause fatigue has led to the development of nutritional
      strategies to enhance performance. Until recently, little was known about CNS
      mechanisms of fatigue, even though the inability or unwillingness to generate and
      maintain central activation of muscle is the most likely explanation of fatigue
      for most people during normal daily activities. A possible role of nutrition in
      central fatigue is receiving more attention with the development of theories that
      provide a clue to its biological mechanisms. The focus is on the neurotransmitter
      serotonin [5-hydroxytryptamine (5-HT)] because of its role in depression, sensory
      perception, sleepiness, and mood. Nutritional strategies have been designed to
      alter the metabolism of brain 5-HT by affecting the availability of its amino
      acid precursor. Increases in brain 5-HT concentration and overall activity have
      been associated with increased physical and perhaps mental fatigue during
      endurance exercise. Carbohydrate (CHO) or branched-chain amino acid (BCAA)
      feedings may attenuate increases in 5-HT and improve performance. However, it is
      difficult to distinguish between the effects of CHO on the brain and those on the
      muscles themselves, and most studies involving BCAA show no performance benefits.
      It appears that important relations exist between brain 5-HT and central fatigue.
      Good theoretical rationale and data exist to support a beneficial role of CHO and
      BCAA on brain 5-HT and central fatigue, but the strength of evidence is presently
      weak.

PMID- 10919961
TI  - Fluid and electrolyte supplementation for exercise heat stress.
AB  - During exercise in the heat, sweat output often exceeds water intake, resulting
      in a body water deficit (hypohydration) and electrolyte losses. Because daily
      water losses can be substantial, persons need to emphasize drinking during
      exercise as well as at meals. For persons consuming a normal diet, electrolyte
      supplementation is not warranted except perhaps during the first few days of heat
      exposure. Aerobic exercise is likely to be adversely affected by heat stress and
      hypohydration; the warmer the climate the greater the potential for performance
      decrements. Hypohydration increases heat storage and reduces a person's ability
      to tolerate heat strain. The increased heat storage is mediated by a lower
      sweating rate (evaporative heat loss) and reduced skin blood flow (dry heat loss)
      for a given core temperature. Heat-acclimated persons need to pay particular
      attention to fluid replacement because heat acclimation increases sweat losses,
      and hypohydration negates the thermoregulatory advantages conferred by
      acclimation. It has been suggested that hyperhydration (increased total body
      water) may reduce physiologic strain during exercise heat stress, but data
      supporting that notion are not robust. Research is recommended for 3 populations
      with fluid and electrolyte balance problems: older adults, cystic fibrosis
      patients, and persons with spinal cord injuries.

PMID- 10919963
TI  - Calcium requirements of physically active people.
AB  - Dietary calcium and physical activity have been independently, but
      inconsistently, associated with the development of increased peak bone mass and
      reduced bone loss later in life. An examination of the literature points to
      important effects of dietary calcium on bone health. During the development of
      peak bone mass, calcium intakes of <1 g/d are associated with lower bone mineral
      density. At intakes approaching calcium requirements, physical activity is a more
      important predictor of bone mineral density than is calcium intake. In studies of
      postmenopausal women, calcium intakes of 1 g (25 mmol/d) appear to be necessary
      to effect a positive impact of exercise on bone mineral density in the spine.
      Calcium intakes recommended for protecting bone health appear to be adequate to
      protect against other disorders with an etiology that includes inadequate dietary
      calcium. Calcium requirements as modified by physical activity need to be
      determined for each population subgroup according to sex, age, race, and cultural
      environment.

PMID- 10919964
TI  - Magnesium, zinc, and chromium nutriture and physical activity.
AB  - Magnesium, zinc, and chromium are mineral elements required in modest amounts to
      maintain health and optimal physiologic function. For physically active persons,
      adequate amounts of these micronutrients are needed in the diet to ensure the
      capacity for increased energy expenditure and work performance. Most physically
      active individuals consume diets that provide amounts of magnesium and zinc
      sufficient to meet population standards. Women tend to consume less of these
      minerals than is recommended, in part because they eat less food than men.
      Inadequate intakes of magnesium and zinc have been reported for participants in
      activities requiring restriction of body weight. Dietary chromium is difficult to
      estimate because of a lack of appropriate reference databases. Acute, intense
      activity results in short-term increases in both urine and sweat losses of
      minerals that apparently diminish during recovery in the days after exercise.
      Supplemental magnesium and zinc apparently improve strength and muscle
      metabolism. However, evidence is lacking as to whether these observations relate
      to impaired nutritional status or a pharmacologic effect. Chromium
      supplementation of young men and women does not promote muscle accretion, fat
      loss, or gains in strength. Physically active individuals with concerns about
      meeting guidelines for nutrient intake should be counseled to select and consume
      foods with high nutrient densities rather than to rely on nutritional
      supplements. The indiscriminate use of mineral supplements can adversely affect
      physiologic function and impair health.

PMID- 10919965
TI  - Iron status and exercise.
AB  - The prevalence of iron deficiency anemia is likely to be higher in athletic
      populations and groups, especially in younger female athletes, than in healthy
      sedentary individuals. In anemic individuals, iron deficiency often not only
      decreases athletic performance but also impairs immune function and leads to
      other physiologic dysfunction. Although it is likely that dietary choices explain
      much of a negative iron balance, evidence also exists for increased rates of red
      cell iron and whole-body iron turnover. Other explanations of decreased
      absorption and increased sweat or urine losses are unlikely. The young female
      athlete may want to consider use of low-dose iron supplements under medical and
      dietary supervision to prevent a decline in iron status during training.

PMID- 10919966
TI  - Effect of physical activity on thiamine, riboflavin, and vitamin B-6
      requirements.
AB  - Because exercise stresses metabolic pathways that depend on thiamine, riboflavin,
      and vitamin B-6, the requirements for these vitamins may be increased in athletes
      and active individuals. Theoretically, exercise could increase the need for these
      micronutrients in several ways: through decreased absorption of the nutrients; by
      increased turnover, metabolism, or loss of the nutrients; through biochemical
      adaptation as a result of training that increases nutrient needs; by an increase
      in mitochondrial enzymes that require the nutrients; or through an increased need
      for the nutrients for tissue maintenance and repair. Biochemical evidence of
      deficiencies in some of these vitamins in active individuals has been reported,
      but studies examining these issues are limited and equivocal. On the basis of
      metabolic studies, the riboflavin status of young and older women who exercise
      moderately (2.5-5 h/wk) appears to be poorer in periods of exercise, dieting, and
      dieting plus exercise than during control periods. Exercise also increases the
      loss of vitamin B-6 as 4-pyridoxic acid. These losses are small and concomitant
      decreases in blood vitamin B-6 measures have not been documented. There are no
      metabolic studies that have compared thiamine status in active and sedentary
      persons. Exercise appears to decrease nutrient status even further in active
      individuals with preexisting marginal vitamin intakes or marginal body stores.
      Thus, active individuals who restrict their energy intake or make poor dietary
      choices are at greatest risk for poor thiamine, riboflavin, and vitamin B-6
      status.

PMID- 10919967
TI  - Does dietary creatine supplementation play a role in skeletal muscle metabolism
      and performance?
AB  - Fatigue sustained during short-term, high-intensity exercise in humans is
      associated with the inability of skeletal muscle to maintain a high rate of
      anaerobic ATP production from phosphocreatine hydrolysis. Ingestion of creatine
      monohydrate at a rate of 20 g/d for 5-6 d was shown to increase the total
      creatine concentration of human skeletal muscle by approximately 25 mmol/kg dry
      mass, some 30% of this in phosphorylated form as phosphocreatine. A positive
      relation was then shown between muscle creatine uptake and improvements in
      performance during repeated bouts of maximal exercise. However, there is no
      evidence that increasing intake > 20-30 g/d for 5-6 d has any potentiating effect
      on creatine uptake or performance. In individuals in whom the initial total
      creatine concentration already approached 150 mmol/kg dry mass, neither creatine
      uptake nor an effect on phosphocreatine resynthesis or performance was found
      after supplementation. Loss of ATP during heavy anaerobic exercise was found to
      decline after creatine ingestion, despite an increase in work production. These
      results suggest that improvements in performance are due to parallel improvements
      in ATP resynthesis during exercise as a consequence of increased phosphocreatine
      availability. Creatine uptake is augmented by combining creatine supplementation
      with exercise and with carbohydrate ingestion.

PMID- 10919969
TI  - Selected herbals and human exercise performance.
AB  - Herbs have been used throughout history to enhance physical performance, but
      scientific scrutiny with controlled clinical trials has only recently been used
      to study such effects. The following herbs are currently used to enhance physical
      performance regardless of scientific evidence of effect: Chinese, Korean, and
      American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha;
      rhodiola; yohimbe; CORDYCEPS: fungus, shilajit or mummio; smilax; wild oats;
      Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; beta
      sitosterol and other related sterols; and wild yams (diosgenin). Controlled
      studies of Asian ginsengs found improvements in exercise performance when most of
      the following conditions were true: use of standardized root extracts, study
      duration (>8 wk, daily dose >1 g dried root or equivalent, large number of
      subjects, and older subjects. Improvements in muscular strength, maximal oxygen
      uptake, work capacity, fuel homeostasis, serum lactate, heart rate, visual and
      auditory reaction times, alertness, and psychomotor skills have also been
      repeatedly documented. Siberian ginseng has shown mixed results. Mahuang,
      ephedrine, and related alkaloids have not benefited physical performance except
      when combined with caffeine. Other herbs remain virtually untested. Future
      research on ergogenic effects of herbs should consider identity and amount of
      substance or presumed active ingredients administered, dose response, duration of
      test period, proper experimental controls, measurement of psychological and
      physiologic parameters (including antioxidant actions), and measurements of
      performance pertinent to intended uses.

PMID- 10919968
TI  - Supplemental carnitine and exercise.
AB  - Carnitine is an endogenous compound with well-established roles in intermediary
      metabolism. An obligate for optimal mitochondrial fatty acid oxidation, it is a
      critical source of energy and also protects the cell from acyl-CoA accretion
      through the generation of acylcarnitines. Carnitine homeostasis is affected by
      exercise in a well-defined manner because of the interaction of the carnitine
      acylcarnitine pool with key metabolic pathways. Carnitine supplementation has
      been hypothesized to improve exercise performance in healthy humans through
      various mechanisms, including enhanced muscle fatty acid oxidation, altered
      glucose homeostasis, enhanced acylcarnitine production, modification of training
      responses, and altered muscle fatigue resistance. Available experimental clinical
      studies designed to assess the effect of carnitine on exercise metabolism or
      performance in healthy humans do not permit definitive conclusions to be drawn.
      In the aggregate, however, these studies suggest that carnitine supplementation
      does not improve maximal oxygen uptake or metabolic status during exercise in
      healthy humans. Carnitine administration for </=1 mo in humans increases plasma
      carnitine concentrations but does not increase muscle carnitine content.
      Additional clinical trials integrating physiologic, biochemical, and
      pharmacologic assessments are needed to definitively clarify any effects of
      carnitine on exercise performance in healthy persons.

PMID- 10919970
TI  - Antioxidants: what role do they play in physical activity and health?
AB  - Exercise appears to increase reactive oxygen species, which can result in damage
      to cells. Exercise results in increased amounts of malondialdehyde in blood and
      pentane in breath; both serve as indirect indicators of lipid peroxidation.
      However, not all studies report increases; these equivocal results may be due to
      the large intersubject variability in response or the nonspecificity of the
      assays. Some studies have reported that supplementation with vitamins C and E,
      other antioxidants, or antioxidant mixtures can reduce symptoms or indicators of
      oxidative stress as a result of exercise. However, these supplements appear to
      have no beneficial effect on performance. Exercise training seems to reduce the
      oxidative stress of exercise, such that trained athletes show less evidence of
      lipid peroxidation for a given bout of exercise and an enhanced defense system in
      relation to untrained subjects. Whether the body's natural antioxidant defense
      system is sufficient to counteract the increase in reactive oxygen species with
      exercise or whether additional exogenous supplements are needed is not known,
      although trained athletes who received antioxidant supplements show evidence of
      reduced oxidative stress. Until research fully substantiates that the long-term
      use of antioxidants is safe and effective, the prudent recommendation for
      physically active individuals is to ingest a diet rich in antioxidants.

PMID- 10919971
TI  - Vitamin E, vitamin C, and exercise.
AB  - Exercise increases the generation of oxygen free radicals and lipid peroxidation.
      Strenuous exercise in a person who is unconditioned or unaccustomed to exercise
      will induce oxidative damage and result in muscle injury. However, aerobic
      exercise training strengthens the antioxidant defense system by increasing
      superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease
      the exercise-induced increase in the rate of lipid peroxidation. No ergogenic
      effects of either vitamin C or E have been shown. Vitamin E was shown to
      significantly increase circulating neutrophils in older, but not younger,
      subjects performing eccentric exercise that causes an increase in skeletal muscle
      damage. In addition to its effect in augmenting the neutrophil response to
      eccentric exercise, vitamin E causes a greater increase in circulating creatine
      kinase activity, perhaps indicating increased skeletal muscle repair. Increased
      vitamin E intake has been associated with enhanced glucose tolerance and insulin
      action as well as improved lipoprotein status. Future research should examine the
      combined effects of exercise training and vitamins E and C on these health
      related outcomes.

PMID- 10919972
TI  - Thiol homeostasis and supplements in physical exercise.
AB  - Thiols are a class of organic sulfur derivatives (mercaptans) characterized by
      the presence of sulfhydryl residues. In biological systems, thiols have numerous
      functions, including a central role in coordinating the antioxidant defense
      network. Physical exercise may induce oxidative stress. In humans, a consistent
      marker of exercise-induced oxidative stress is blood glutathione oxidation.
      Physical training programs have specific effects on tissue glutathione metabolism
      that depend on the work program and the type of tissue. Experimental studies show
      that glutathione metabolism in several tissues sensitively responds to an
      exhaustive bout of exercise. Study of glutathione-deficient animals clearly
      indicates the central importance of having adequate tissue glutathione to protect
      against exercise-induced oxidative stress. Among the various thiol supplements
      studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These
      agents may have antioxidant effects at the biochemical level but are also known
      to influence redox-sensitive cell signaling.

PMID- 10919973
TI  - Exercise and oxidative stress methodology: a critique.
AB  - Historically, exercise physiologists' interest in oxygen has primarily centered
      on the problem of oxygen consumption. However, the interest of the general
      scientific community in oxygen-centered radicals has raised awareness of the
      oxygen paradox and has motivated investigators to question whether exercise
      stimulated "overconsumption" of oxygen might induce an oxidative stress and pose
      some risk to biological systems. In recent years, a considerable amount of
      research has demonstrated that radicals are capable of damaging a vast array of
      biological targets. Unfortunately, the work related to oxidative stress and
      antioxidants subsequent to exercise has been narrow in scope. This paper provides
      a brief review of the shortcomings of the present state of knowledge in this
      discipline and outlines topics requiring attention.

PMID- 10919974
TI  - Inflammation and infection in naive human cystic fibrosis airway grafts.
AB  - Exacerbated inflammation is now recognized as an important component of cystic
      fibrosis (CF) airway disease. Whether inflammation is part of the basic defect in
      CF or a response to persistent infection remains controversial. We addressed this
      question using human fetal tracheal grafts in severe combined immunodeficient
      mice. This model yields histologically mature, and most importantly, naive CF and
      non-CF surrogate airways. Significant inflammatory imbalance was found in naive
      CF airway grafts, including a highly increased intraluminal interleukin 8 content
      (CF: 10.1 +/- 2.2 ng/ml; non-CF: 1.2 +/- 0.6 ng/ml; P < 0.05) and consistent
      accumulation of leukocytes in the subepithelial region (P < 0.001). CF airway
      grafts were not histologically affected until challenged with Pseudomonas
      aeruginosa, which provoked: (1) early (before 3 h) and massive leukocyte
      transepithelial migration, (2) intense epithelial exfoliation, and (3) rapid
      progression of bacteria toward the lamina propria. In non-CF grafts, these three
      sets of events were not observed before 6 h. Using a model of naive human
      airways, we thus demonstrate that before any infection, CF airways are in a
      proinflammatory state. After infection, the basal inflammatory imbalance
      contributes to exert severe damage to the mucosa, paving the way for bacterial
      colonization and subsequent steps of CF airway disease.

PMID- 10919975
TI  - Recognition of bacterial endotoxin in the lungs.

PMID- 10919976
TI  - CD11/CD18-dependent and -independent neutrophil emigration in the lungs: how do
      neutrophils know which route to take?

PMID- 10919977
TI  - Retinoid-enhanced alveolization: identifying relevant downstream targets.

PMID- 10919978
TI  - Mesenchymal regulation of alveolar repair in pulmonary fibrosis.

PMID- 10919979
TI  - Production of the acute-phase protein lipopolysaccharide-binding protein by
      respiratory type II epithelial cells: implications for local defense to bacterial
      endotoxins.
AB  - This study demonstrates for the first time that respiratory epithelial cells are
      able to produce the acute phase protein lipopolysaccharide (LPS)-binding protein
      (LBP), which is known to play a central role in the defense to bacterial
      endotoxins (or LPS). Indications for local presence of LBP in human lung was
      obtained via reverse transcriptase/polymerase chain reaction that showed LBP
      messenger RNA (mRNA) expression. Therefore, LBP production by the human lung
      epithelial cell line A549, a human adenocarcinoma with features of type II
      pneumocytes, was studied. These cells produced LBP in response to interleukin
      (IL)-1beta, IL-6, and tumor necrosis factor- alpha, a response that was strongly
      enhanced by dexamethasone. In addition, LBP mRNA was detected in A549 cells, in
      increasing amounts as a result of stimulation. The pattern of cytokine-induced
      LBP production in A549 cells was similar to the pattern in the human liver
      epithelial cell line HuH-7. Moreover, the molecular weight of A549-derived LBP
      was approximately 60 kD, which is similar to HuH-7-derived LBP. Biologic activity
      of LBP produced by A549 cells was evaluated on the basis of its ability to
      interact with LPS. Further indications that type II alveolar epithelial cells are
      able to produce LBP were obtained from the observations that the murine lung type
      II epithelial cell line C10 produced murine LBP, and that isolated human primary
      type II pneumocytes expressed LBP mRNA, which was enhanced after stimulation of
      cells. The local production of this endotoxin binding protein by lung epithelial
      cells might contribute to a highly specific response at the site of exposure to
      bacteria and bacterial endotoxins.

PMID- 10919980
TI  - Interleukin-8 and leukotriene-B(4), but not formylmethionyl leucylphenylalanine,
      stimulate CD18-independent migration of neutrophils across human pulmonary
      endothelial cells in vitro.
AB  - Although neutrophil migration from the systemic circulation involves the beta2-
      (or CD18) integrin family, the existence of an alternative, CD18-independent
      route of neutrophil extravasation to tissues has been demonstrated in animal
      models. The molecular interactions involved in this alternative migratory route
      have not yet been characterized. The objective of this study was to assess the
      CD18-dependency of neutrophil migration across human endothelial cells from an
      organ known to support CD18-independent migration, the lung, with a view to
      establishing an in vitro model to facilitate study of CD18-independent migration.
      Neutrophil migration across human pulmonary artery endothelial cells (HPAECs) in
      response to three different chemoattractants, formylmethionyl leucylphenyl
      alanine (FMLP), interleukin (IL)-8, and leukotriene (LT) B(4), was examined.
      Results demonstrated that a function-blocking antibody to CD18 decreased FMLP
      stimulated migration by 71.7 +/- 4.4% (P < 0.001). In contrast, migration in
      response to LTB(4) was decreased by only 20.5 +/- 10.2% (P < 0.01), and no
      significant decrease was observed with migration to IL-8. Neutrophils that
      migrated to FMLP had 1.7-fold more surface CD11b/CD18 compared with nonmigrated
      neutrophils (P < 0.01), whereas this integrin complex was not significantly
      upregulated on neutrophils that had migrated to IL-8 or LTB(4). Further
      investigation of this migratory route indicated that it did not involve the beta1
      integrins (CD29) or the endothelial selectins, E- or P-selectin, nor did it
      require the activity of either metalloproteinases or neutrophil elastase. These
      results indicate that neutrophil migration across HPAECs in vitro to IL-8 and
      LTB(4) is predominantly CD18-independent and provides a much-needed in vitro
      system for examination of the neutrophil-endothelial interactions involved in
      this alternative migratory route.

PMID- 10919981
TI  - Mice bearing deletions of retinoic acid receptors demonstrate reduced lung
      elastin and alveolar numbers.
AB  - In mammals, including rats and mice, the development of pulmonary alveolar septa
      is primarily limited to late gestation and the early periods of postnatal life.
      Before this time, the rat lung contains a relatively large supply of endogenous
      retinyl ester that, together with its metabolite retinoic acid, has been shown to
      increase elastin gene expression and the number of alveoli. We have hypothesized
      that mice bearing a deletion of one or more genes encoding for retinoic acid
      receptors (which are DNA binding proteins that alter transcription of retinoic
      acid-responsive genes) may demonstrate abnormalities in retinoid-mediated
      alveolar formation. Our studies demonstrate that the absence of the retinoic acid
      receptor-gamma (RARgamma) is associated with a decrease in the steady-state level
      of tropoelastin messenger RNA in a subpopulation of lung fibroblasts at Postnatal
      Day 12. RARgamma gene deletion also resulted in a decrease in whole lung elastic
      tissue and alveolar number, and an increase in mean cord length of alveoli (L(m))
      at Postnatal Day 28. The additional deletion of one retinoid X receptor
      (RXR)alpha allele resulted in a decrease in alveolar surface area and alveolar
      number, and an increase in L (m). These data indicate that RARgamma is required
      for the formation of normal alveoli and alveolar elastic fibers in the mouse, and
      that RAR/RXR heterodimers are involved in alveolar morphogenesis.

PMID- 10919982
TI  - Increased expression of epimorphin in bleomycin-induced pulmonary fibrosis in
      mice.
AB  - Epimorphin was originally identified as a mesenchymal, cell surface-associated
      protein that modulates epithelial morphogenesis in embryonic organs, whereas
      pulmonary fibrosis is a process of wound healing, which in part mimics the
      process of fetal lung development. We investigated the temporal and spatial
      changes in the distribution of epimorphin protein and expression of its messenger
      RNA (mRNA) in bleomycin-induced pulmonary fibrosis in mice. Immunohistochemical
      analysis showed that low levels of epimorphin were present in the bronchiolar,
      alveolar, and vascular walls of normal adult lungs. However, from Day 7 until Day
      28 after bleomycin treatment, increasing levels of epimorphin immunoreactivity
      were detected in the mesenchymal cells and in the extracellular matrix within
      intra-alveolar fibrotic lesions. Moreover, Northern blots showed corresponding
      increases in epimorphin mRNA expression. Re-epithelialization of epimorphin-rich
      intra-alveolar fibrosis was complete by Day 28 after bleomycin, and by Day 56,
      epimorphin immunoreactivity had declined. In situ hybridization and confocal
      microscopic studies confirmed expression of epimorphin mRNA by mesenchymal cells
      situated within early fibrotic lesions, whereas immunoelectron microscopy
      localized the epimorphin to the endoplasmic reticulum of the mesenchymal cells
      and to the basement membrane and collagen fibrils in the area. These results
      suggest that epimorphin may contribute to the remodeling of pulmonary fibrosis
      via epithelial-mesenchymal interactions.

PMID- 10919983
TI  - Regulation of ciliary beat frequency by the nitric oxide-cyclic guanosine
      monophosphate signaling pathway in rat airway epithelial cells.
AB  - Nitric oxide (NO) upregulates ciliary beat frequency (CBF). The present study
      evaluates mechanisms of the NO-cyclic guanosine monophosphate (cGMP) pathway
      regulation of CBF. Rat tracheal explants were loaded with 4,5-diaminofluorescein
      diacetate for the demonstration of NO production by ciliated epithelial cells
      after L-arginine (L-Arg) stimulation. CBF was measured using phase contrast
      microscopy and videotape analysis. The roles of NO, soluble guanylate cyclase
      (sGC), cGMP-dependent protein kinase (PK) G, and phosphodiesterase (PDE) V in
      regulation of CBF were evaluated. NO synthase (NOS) was activated with L-Arg or
      inhibited with N(G)-monomethyl-L-Arg. sGC was stimulated with NO donors 1-hydroxy
      2-oxo-3- (N-ethyl-2-aminoethyl)-3-ethyl-1-triazene and S-nitroso-L-glutathione or
      mimicked by 8-bromo-guanosine 3', 5'-cyclic monophosphate (8-Br-cGMP) and
      inhibited with 1H-[1,2, 4]oxadiazole[4,3-a]quinoxalin-1-one. The effects of the
      PKG inhibition with KT5823 and PDE V inhibition with Zaprinast were also
      examined. The studies demonstrate that ciliated epithelial cells produce NO,
      which is correlated with CBF stimulation. L-Arg dose- and time-dependently
      increases CBF, and NO donors, 8-Br-cGMP, and Zaprinast also enhance CBF.
      Inhibitors of NOS, sGC, and PKG can block the stimulant effect of L-Arg on CBF.
      Thus, NO is a regulator of CBF acting via sGC and PKG. The NO-cGMP signaling
      pathway regulates CBF in an autocrine manner in cultured rat ciliated airway
      epithelium.

PMID- 10919984
TI  - Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB
      related genes and oxidant-dependent NF-kappaB activation in vitro.
AB  - High levels of ambient air pollution are associated with exacerbation of asthma
      and respiratory morbidity, yet little is known concerning the mechanisms of
      inflammation and toxicity by components of inhaled particulate matter (PM). Brief
      inhalation of PM(2.5) (particles of an aerodynamic diameter of < 2.5 microns)
      (300 microg/m(3) air for 6 h followed by a period of 24 h in clean air) by either
      C3H/HeJ or C57/BL6 mice caused significant (P </= 0.05) increases in steady-state
      messenger RNA (mRNA) levels of a number of nuclear factor (NF)-kappaB-associated
      and/ or -regulated genes, including tumor necrosis factor-alpha and -beta,
      interleukin-6, interferon-gamma, and transforming growth factor-beta. Lung mRNA
      levels of lymphotoxin-beta and macrophage migration inhibitory factor were
      unchanged. In murine C10 alveolar cells and an NF-kappaB-luciferase reporter cell
      line, exposure to PM(2.5) at noncytotoxic concentrations resulted in increases in
      transcriptional activation of NF-kappaB-dependent gene expression which were
      inhibited in the presence of catalase. Early and persistent increases in
      intracellular oxidants, as measured by flow cytometry and cell imaging using the
      oxidant probe 2'-7'-dichlorofluoroscin diacetate, were observed in epithelial
      cells exposed to PM(2.5) and ultrafine carbon black particles. Studies here are
      the first to show NF-kappaB-related inflammatory and cytokine gene expression
      after inhalation of PM(2.5) and oxidant-dependent induction of NF-kappaB activity
      by PM(2.5) in pulmonary epithelial cells.

PMID- 10919985
TI  - A novel nonclassic beta2-microglobulin-restricted mechanism influencing early
      lymphocyte accumulation and subsequent resistance to tuberculosis in the lung.
AB  - In this study, we compared the course of a low-dose aerosol Mycobacterium
      tuberculosis infection in mice bearing gene disruptions for the beta2
      microglobulin molecule, the CD8 molecule, and the CD1 molecule. Over the first 50
      d of infection, the CD8- and CD1-disrupted mice were no more susceptible to
      infection than were the control mice. In contrast, the bacterial load in beta2
      microglobulin gene-disrupted mice increased rapidly and attained much higher
      levels than that observed in the other gene-disrupted mice and in control mice. A
      second major difference between the beta2-microglobulin gene-disrupted mice and
      the other animals was the development of lung granulomas; both the CD8- and CD1
      disrupted mice developed essentially normal granulomas except for an apparent
      increased lymphocyte influx in the CD8-disrupted mice. The beta2-microglobulin
      gene-disrupted mice, on the other hand, developed granulomas virtually devoid of
      lymphocytes, with these cells instead localized within prominent perivascular
      cuffing adjacent to the lesions. These data support the hypothesis that a beta2
      microglobulin-dependent, non-CD8- and non-CD1-dependent mechanism controls the
      early and efficient influx of protective lymphocytes into infected lesions, and
      that the absence of this mechanism decreases the capacity of the animal to
      initially deal with pulmonary tuberculosis.

PMID- 10919986
TI  - Prenatal origins of human intrapulmonary arteries: formation and smooth muscle
      maturation.
AB  - Recent studies on the morphogenesis of the pulmonary arteries have focused on
      nonhuman species such as the chick and the mouse. Using immunohistochemical
      techniques, we have studied 16 lungs from human embryos and fetuses from 28 d of
      gestation to newborn, using serial sections stained with a panel of antibodies
      specific for endothelium, smooth muscle, and extracellular matrix proteins. Cell
      replication was also assessed. Serial reconstruction showed a continuity of
      circulation between the heart and the capillary plexus from at least 38 d of
      gestation. The intrapulmonary arteries appeared to be derived from a continuous
      expansion of the primary capillary plexus that is from within the mesenchyme, by
      vasculogenesis. The arteries formed by continuous coalescence of endothelial
      tubes alongside the newly formed airway. Findings were consistent with the
      pulmonary arterial smooth muscle cells being derived from three sites in a
      temporally distinct sequence: the earliest from the bronchial smooth muscle,
      later from the mesenchyme surrounding the arteries, and last from the endothelial
      cells. Despite their different origins, all smooth muscle cells followed the same
      sequence of expression of smooth muscle-specific cytoskeletal proteins with
      increasing age. The order of appearance of these maturing proteins was from the
      subendothelial cells outward across the vessel wall and from hilum to periphery.
      The airways would seem to act as a template for pulmonary artery development.
      This study provides a framework for studying the signaling mechanisms controlling
      the various aspects of lung development.

PMID- 10919987
TI  - A CD36 synthetic peptide inhibits bleomycin-induced pulmonary inflammation and
      connective tissue synthesis in the rat.
AB  - Transforming growth factor (TGF)-beta1 is an important regulator of inflammation
      and fibrosis. TGF-beta1 is usually secreted as a biologically latent protein
      called latent TGF-beta1 (L-TGF-beta1). L-TGF-beta1 has no biologic effect unless
      L-TGF-beta1 is converted to its active form. Using a well-recognized model of
      lung injury induced by the antineoplastic antibiotic bleomycin (Blm), we
      demonstrated that 7 d after intratracheal Blm administration, total lung TGF-beta
      was maximally increased. This induction was due to TGF-beta1 production by
      alveolar macrophages that, when explanted, generated increased quantities of L
      TGF-beta1 complexed with the glycoprotein thrombospondin (TSP)-1. The TSP-1/L-TGF
      beta1 complex was associated with CD36, a receptor for TSP-1. The association of
      TSP-1/L-TGF-beta1 to CD36 was critical for plasmin-mediated release of mature TGF
      beta1. In this paper we show that, compared with administration of Blm by itself,
      when a synthetic peptide of CD36 between amino acids 93 and 110 is given
      concomitantly with Blm to rats, alveolar macrophages generate markedly less
      active TGF-beta1, the rats gain weight more rapidly, and there is less
      inflammation, collagen I and III, and fibronectin synthesis. These findings
      demonstrate a novel in vivo mechanism of activation of L-TGF-beta1 in lung injury
      and the importance of alveolar macrophage- derived active TGF-beta1 in the
      pathogenesis of pulmonary inflammation and fibrosis.

PMID- 10919988
TI  - Endothelin-1 is a potent activator of nonselective cation currents in human
      bronchial smooth muscle cells.
AB  - The effects of endothelin (ET)-1 on cultured human bronchial smooth muscle cells
      (HBSMC) were investigated and compared with those of histamine, using the patch
      clamp techniques and measurements of intracellular Ca(2+) ([Ca(2+)](i)). Both ET
      1 and histamine caused an initial transient elevation of [Ca(2+)](i) by Ca(2+)
      mobilization, followed by a sustained rise due to Ca(2+) entry. Nicardipine
      inhibited the sustained phase, but La(3+) abolished it. With low ethyleneglycol
      bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA) and K(+) internal
      solutions, both ET-1 and histamine induced a sustained depolarization from
      approximately -40 to -20 mV. Under voltage clamp conditions, both drugs
      transiently activated an outward K(+) current at a holding potential of 0 mV.
      Additionally, with a Cs(+) internal solution, they elicited another transient
      inward current, frequently followed by current oscillations. These transient
      currents were blocked by high EGTA or heparin. With high EGTA and Cs(+) internal
      solutions, both drugs activated a long-lasting inward current. The reversal
      potential of these agonist-induced currents was approximately 0 mV and was not
      altered by the replacement of internal or external concentration of Cl(-),
      suggesting that the inward current was a nonselective cation current (I(cat)).
      The half-maximal effective concentration to activate I(cat) was 12 nM for ET-1
      and 11 microM for histamine. La(3+) and Cd(2+) abolished these agonist-induced
      I(cat). The effects of ET-1 on [Ca(2+)](i) and I(cat) could be blocked by
      combined pretreatment with BQ-123 and BQ-788. Sarafotoxin S6c also increased
      [Ca(2+)](i) and activated I(cat). By polymerase chain reaction of reverse
      transcribed RNA, we detected both ET-A and ET-B receptor messenger RNA. These
      results provide the first evidence that ET-1 is a potent activator of I(cat) in
      HBSMC via ET-A and ET-B receptors, and the activation of I(cat) plays an
      important role in ET-1-induced Ca(2+) entry in human airways.

PMID- 10919989
TI  - Nitric oxide (NO)-dependent but not NO-independent guanylate cyclase activation
      attenuates hypoxic vasoconstriction in rabbit lungs.
AB  - Hypoxic pulmonary vasoconstriction (HPV) is essential for matching lung perfusion
      with ventilation, thus optimizing pulmonary gas exchange. Preceding studies
      provided evidence for a role of both nitric oxide (NO) and superoxide/ H(2)O(2)
      formation in this vasoregulatory mechanism. Both agents might be operative via
      stimulation of guanylate cyclase with formation of the vasodilatory cyclic
      guanosine monophosphate (cGMP), the loss of which under conditions of hypoxia
      contributes to HPV. This view is challenged by the recent suggestion of increased
      rather than decreased superoxide/H(2)O(2) formation in hypoxia. We addressed the
      role of NO-dependent versus NO-independent guanylate cyclase activity in hypoxic
      and pharmacologically evoked vasoconstriction in perfused rabbit lungs. Two
      inhibitors of soluble guanylate cyclase, LY83583 (2 to 16 microM) and methylene
      blue (20 to 60 microM), increased baseline pulmonary artery pressure under
      normoxic conditions and markedly amplified the vasoconstrictor response to both
      hypoxia and the stable thromboxane analogue U46619. Under conditions of
      preblocked lung NO synthesis (N(G)-mono-methyl-L-arginine), however, additional
      guanylate cyclase inhibition further enhanced the vasoconstrictor response to
      U46619 but did not influence the strength of HPV. The selective phosphodiesterase
      V inhibitor Zaprinast (1 to 10 microM), used for prolongation of the cGMP half
      life, reduced the hypoxia-induced pressor response to a larger extent than the
      pressor response to U46619. This difference was lost under conditions of
      preblocked NO synthesis. Equilibration of the lung perfusate with molecular NO
      suppressed the HPV more potently than the U46619-induced vasoconstrictor
      response. We conclude that NO-dependent guanylate cyclase activity has an
      important role in attenuating the vasoconstrictor response to alveolar hypoxia in
      rabbit lungs. In contrast, no evidence was obtained for a role of NO-independent
      cGMP formation in HPV. In this feature, HPV differs from that elicited by the
      thromboxane analogue U46619.

PMID- 10919990
TI  - Priming of allergic immune responses by repeated ozone exposure in mice.
AB  - The effects of repeated ozone exposures on the development of immune responses
      toward ovalbumin (OVA) were investigated in BALB/c and C57BL/6 mice. Ozone
      exposures (180 to 500 microg/m(3); 4 h, three times/wk for 4 wk) were combined
      with a protocol of OVA-aerosol exposure (1% OVA). Immediate cutaneous
      hypersensitivity (ICHS) reactions and antibody titers were assessed in parallel
      to cytokine levels of bronchoalveolar lavage fluids. In BALB/c mice, ozone
      triggered a T-helper (Th)2-like response indicated by dose-dependent increases in
      total serum immunoglobulin (Ig) E (from 133 to 821 ng/ml), interleukin (IL)-4
      (from 60 to 208 pg/ml), and IL-5 levels (from 43 to 356 pg/ml), and by the
      recruitment of eosinophils and lymphocytes into the airways. Ozone exposure (500
      microg/m(3)) in parallel to OVA-aerosol exposure increased anti-OVA IgG(1)
      antibody titers by 80%, leukotrienes (C(4)/D(4)/E(4)) by 60%, and airway
      responsiveness (11.3 versus 7.2 mg/ml methacholine), and doubled the frequency of
      positive ICHS reactions. In C57BL/6 mice, only the combination of OVA and ozone
      exposure induced positive ICHS reactions, doubled anti-OVA IgG(1), and suppressed
      anti-OVA IgG(2a) (-64%) antibody titers. Ozone, therefore, shifted the immune
      responses to OVA toward a Th2-like pattern in both "IgE-high responder" (BALB/c)
      and "IgE-low responder" (C57BL/6) mice.

PMID- 10919991
TI  - Sp1 and Sp3 function as key regulators of leukotriene C(4) synthase gene
      expression in the monocyte-like cell line, THP-1.
AB  - The goal of this study was to examine the mechanisms of leukotriene C(4) (LTC(4))
      synthase gene expression in mononuclear phagocytes. Transfection of the monocyte
      like cell line THP-1 with LTC(4) synthase promoter-reporter constructs
      demonstrated that the first 1.3 kb of the promoter mediated a 21.1-fold increase
      in reporter activity. Deletion analysis revealed that the region between -92 and 
      23 bp, which contains a signal protein (Sp)1 consensus site at -42 to -37 bp,
      mediated an 11.5-fold increase in reporter activity. Using a probe from -56 to 
      17 bp, electrophoretic mobility shift assays (EMSAs) demonstrated that Sp1 and
      THP-1 and HeLa nuclear extracts bind to this region. Binding was eliminated by
      mutation of the Sp1 consensus site. Supershift EMSAs using anti-Sp1 and anti-Sp3
      antibodies demonstrated that these Sp family members bind to the region.
      Transfection of the Sp-deficient Drosophila SL-2 cell line with a construct
      containing the -92 to -23 bp promoter region and Sp expression vectors revealed
      that Sp1 and Sp3 transactivate gene transcription. We conclude that the Sp1 site
      is a necessary element for LTC(4) synthase gene transcription. Sp1 and Sp3
      function through this site to positively regulate transcription. Thus, we provide
      evidence that the LTC(4) synthase gene is transcriptionally regulated in
      mononuclear phagocytes.

PMID- 10919992
TI  - Airway subepithelial fibrosis in a murine model of atopic asthma: suppression by
      dexamethasone or anti-interleukin-5 antibody.
AB  - Fibrosis in the reticular layer beneath the epithelial basement membrane is a
      feature of airway remodeling in human asthma. We previously reported the presence
      of subepithelial fibrosis (SEF) in a disease model of atopic asthma in which mice
      were sensitized and intratracheally challenged with ovalbumin (OVA) (Blyth and
      colleagues, Am. J. Respir. Cell Mol. Biol. 1996;14:425-438). Here, we describe
      further studies to quantify the degree of SEF after its induction by repeated
      exposure of the airways to allergen. The amount of subepithelial reticulin in the
      airways of animals challenged three times with 80 microg OVA was typically
      increased 1. 4-fold. The increased amount of reticulin showed no reduction after
      a 50-d period after the third allergen challenge. A reduction in SEF was achieved
      by daily treatment with dexamethasone (DEX) for 8 d during the allergen challenge
      period, or by treatment with anti-interleukin-5 antibody (TRFK5) at the time of
      allergen challenge. Postchallenge treatment with DEX for 15 d resulted in
      significant resolution of previously established SEF. Severe nonallergic
      inflammation during repeated exposure of airways to lipopolysaccharide did not
      induce SEF. The results indicate that development of SEF is associated with
      eosinophil infiltration into airways, and may occur only when the inflammatory
      stimulus is allergic in nature.

PMID- 10919993
TI  - Synergistic effect of diesel organic extracts and allergen Der p 1 on the release
      of chemokines by peripheral blood mononuclear cells from allergic subjects:
      involvement of the map kinase pathway.
AB  - The organic compounds of diesel exhaust particles (DEP-PAHs) have been shown to
      favor immunoglobulin production and bronchial hyperresponsiveness and to affect
      cytokine and chemokine productions. To evaluate if diesel exhaust could act in
      synergy with a house dust mite allergen (Der p 1), peripheral blood mononuclear
      cells from allergic patients were exposed to DEP-PAHs, with or without purified
      Der p 1. DEP-PAHs and Der p 1 separately induced an increase in interleukin (IL)
      8, regulated on activation, normal T cells expressed and secreted (RANTES), and
      tumor necrosis factor-alpha concentrations. Interestingly, a synergy between the
      two stimuli was also observed. In the case of monocyte chemotactic protein (MCP)
      1, DEP-PAHs reduced the release, whereas Der p 1 enhanced it. A simultaneous
      exposure led to reduced production as compared with allergen exposure alone, but
      still represented an increase as compared with the control exposure. Mitogen
      activated protein (MAP) kinase Erk1/2 antagonist mainly inhibited the release of
      MCP-1, whereas MAP kinase p38 antagonist mainly suppressed the release of IL-8
      and RANTES. Messenger RNA expression correlated with protein measurements.
      Moreover, supernatants from cells exposed to both DEP-PAHs and Der p 1 had a
      significant chemotactic activity on neutrophils and eosinophils. These findings
      suggest that simultaneous exposure of allergic patients to DEPs and allergens
      could result in high local chemokine levels via MAP kinase pathways activation,
      increasing the likelihood of reaching a critical threshold leading to the
      initiation of respiratory allergic symptoms.

PMID- 10919994
TI  - Biochemical evidence for an ecto alkaline phosphodiesterase I in human airways.
AB  - Because dinucleotides are signaling molecules that can interact with cell surface
      receptors and regulate the rate of mucociliary clearance in lungs, we studied
      their metabolism by using human airway epithelial cells. A membrane-bound enzyme
      was detected on the mucosal surface of polarized epithelia that metabolized
      dinucleotides with a broad substrate specificity (diadenosine polyphosphates and
      diuridine polyphosphates [Up(n)U], n = 2 to 6). The enzymatic reaction yielded
      nucleoside monophosphates (NMP) and Np(n)(-)(1) (N = A or U), and was inhibited
      by nucleoside 5'-triphosphates (alpha,betamet adenosine triphosphate [ATP] > ATP
      >/= uridine triphosphate > guanidine triphosphate > cytidine triphosphate). The
      apparent Michaelis constant (K(m,app)) and apparent maximal velocity (V(max,app))
      for [(3)H]Up(4)U were 22 +/- 4 microM and 0.24 +/- 0.05 nmoles. min(-)(1). cm(
      )(2), respectively. Thymidine 5'-monophosphate p-nitrophenyl ester and adenosine
      diphosphate (ADP)- ribose, substrates of ecto alkaline phosphodiesterase I (PDE
      I) activities, were also hydrolyzed by the apical surface of airway epithelia.
      ADP-ribose competed with [(3)H]Up(4)U, with a K(i) of 23 +/- 3 microM. The
      metabolism of ADP-ribose and Ap(4)A was not affected by inhibitors of cyclic
      nucleotide phosphodiesterases (3-isobutyl-1-methylxanthine, Ro 20-1724, and 1,3
      dipropyl-8-p-sulfophenylxanthine), but similarly inhibited by fluoride and N
      ethylmaleimide. These results suggest that a PDE I is responsible for the
      hydrolysis of extracellular dinucleotides in human airways. The wide substrate
      specificity of PDE I suggests that it may be involved in several signaling events
      on the luminal surface of airway epithelia, including purinoceptor activation and
      cell surface protein ribosylation.

PMID- 10919996
TI  - Elbow flexibility and ligand-induced domain rearrangements in antibody Fab NC6.8:
      large effects of a small hapten.
AB  - Four 700-ps molecular dynamics simulations were carried out to analyze the
      structural dynamics of the antigen-binding antibody fragment NC6.8, which is
      known to exhibit large structural changes upon complexation. The first simulation
      was started from the x-ray structure of the uncomplexed Fab and produced
      trajectory averages that closely match the crystallographic results. It allowed
      assessment of the flexibility of the Fab, revealing an elbow motion of the
      variable domains with respect to the constant domains. The second simulation was
      started from the uncomplexed x-ray structure after insertion of the ligand into
      the binding site. This perturbation resulted in a significantly altered
      trajectory, with quaternary structural changes corresponding in many aspects to
      the experimental differences between complexed and uncomplexed state. The
      observed trend toward a smaller elbow angle and a higher flexion of the H-chain
      could also be seen in the third simulation, which was started from the x-ray
      structure of the complex. The changes were revealed to be a clear consequence of
      the complexation with the ligand because in the fourth simulation (started from
      the experimental complex structure after removal of the hapten) the Fab remained
      close to its initial structure. Analyses of the quaternary structure and the
      binding site of Fab NC6.8 are presented for all four simulations, and possible
      interpretations are discussed.

PMID- 10919997
TI  - Influence of temporal correlation of synaptic input on the rate and variability
      of firing in neurons.
AB  - The spike trains that transmit information between neurons are stochastic. We
      used the theory of random point processes and simulation methods to investigate
      the influence of temporal correlation of synaptic input current on firing
      statistics. The theory accounts for two sources for temporal correlation:
      synchrony between spikes in presynaptic input trains and the unitary synaptic
      current time course. Simulations show that slow temporal correlation of synaptic
      input leads to high variability in firing. In a leaky integrate-and-fire neuron
      model with spike afterhyperpolarization the theory accurately predicts the firing
      rate when the spike threshold is higher than two standard deviations of the
      membrane potential fluctuations. For lower thresholds the spike
      afterhyperpolarization reduces the firing rate below the theory's predicted level
      when the synaptic correlation decays rapidly. If the synaptic correlation decays
      slower than the spike afterhyperpolarization, spike bursts can occur during
      single broad peaks of input fluctuations, increasing the firing rate over the
      prediction. Spike bursts lead to a coefficient of variation for the interspike
      intervals that can exceed one, suggesting an explanation of high coefficient of
      variation for interspike intervals observed in vivo.

PMID- 10919995
TI  - A theoretical model for the prediction of sequence-dependent nucleosome
      thermodynamic stability.
AB  - A theoretical model for predicting nucleosome thermodynamic stability in terms of
      DNA sequence is advanced. The model is based on a statistical mechanical
      approach, which allows the calculation of the canonical ensemble free energy
      involved in the competitive nucleosome reconstitution. It is based on the
      hypothesis that nucleosome stability mainly depends on the bending and twisting
      elastic energy to transform the DNA intrinsic superstructure into the nucleosomal
      structure. The ensemble average free energy is calculated starting from the
      intrinsic curvature, obtained by integrating the dinucleotide step deviations
      from the canonical B-DNA and expressed in terms of a Fourier series, in the
      framework of first-order elasticity. The sequence-dependent DNA flexibility is
      evaluated from the differential double helix thermodynamic stability. A large
      number of free-energy experimental data, obtained in different laboratories by
      competitive nucleosome reconstitution assays, are successfully compared to the
      theoretical results. They support the hypothesis that the stacking energies are
      the major factor in DNA rigidity and could be a measure of DNA stiffness. A dual
      role of DNA intrinsic curvature and flexibility emerges in the determination of
      nucleosome stability. The difference between the experimental and theoretical
      (elastic) nucleosome-reconstitution free energy for the whole pool of
      investigated DNAs suggests a significant role for the curvature-dependent DNA
      hydration and counterion interactions, which appear to destabilize nucleosomes in
      highly curved DNAs. This model represents an attempt to clarify the main features
      of the nucleosome thermodynamic stability in terms of physical-chemical
      parameters and suggests that in molecular systems with a large degree of
      complexity, the average molecular properties dominate over the local features, as
      in a statistical ensemble.

PMID- 10919998
TI  - Biased Brownian dynamics for rate constant calculation.
AB  - An enhanced sampling method-biased Brownian dynamics-is developed for the
      calculation of diffusion-limited biomolecular association reaction rates with
      high energy or entropy barriers. Biased Brownian dynamics introduces a biasing
      force in addition to the electrostatic force between the reactants, and it
      associates a probability weight with each trajectory. A simulation loses weight
      when movement is along the biasing force and gains weight when movement is
      against the biasing force. The sampling of trajectories is then biased, but the
      sampling is unbiased when the trajectory outcomes are multiplied by their
      weights. With a suitable choice of the biasing force, more reacted trajectories
      are sampled. As a consequence, the variance of the estimate is reduced. In our
      test case, biased Brownian dynamics gives a sevenfold improvement in central
      processing unit (CPU) time with the choice of a simple centripetal biasing force.

PMID- 10919999
TI  - Essential motions and energetic contributions of individual residues in a peptide
      bound to an SH3 domain.
AB  - We have studied protein-ligand interactions by molecular dynamics simulations
      using software designed to exploit parallel computing architectures. The
      trajectories were analyzed to extract the essential motions and to estimate the
      individual contributions of fragments of the ligand to overall binding enthalpy.
      Two forms of the bound ligand are compared, one with the termini blocked by
      covalent derivatization, and one in the underivatized, zwitterionic form. The
      ends of the peptide tend to bind more loosely in the capped form. We can observe
      significant motions in the bound ligand and distinguish between motions of the
      peptide backbone and of the side chains. This could be useful in designing
      ligands, which fit optimally to the binding protein. We show that it is possible
      to determine the different contributions of each residue in a peptide to the
      enthalpy of binding. Proline is a major net contributor to binding enthalpy, in
      keeping with the known propensity for this family of proteins to bind proline
      rich peptides.

PMID- 10920000
TI  - Bending and adaptability to proteins of the cAMP DNA-responsive element:
      molecular dynamics contrasted with NMR.
AB  - DNA bending is assumed to play a crucial role during recognition of the cAMP
      responsive element (CRE) by transcription factors. However, diverging results
      have been obtained for the bending direction of the unbound double helix. The
      refined NMR structures present a bend directed toward the minor groove, while
      biochemical methods conclude that there is a bend toward the major groove. The
      present 10-ns molecular dynamics (MD) simulation of d(GAGATGACGTCATCTC)(2), which
      contains the octamer CRE in its center, was carried out with AMBER in explicit
      water and counterions. It shows that CRE is a flexible segment, although it is
      bent slightly toward the major groove (7 degrees -8 degrees ) on the average. The
      MD structure agrees with both the biochemical results and unrefined NMR data. The
      divergence with the NMR refined structures suggests an improper electrostatic
      parameterization in the refinement software. The malleability of the central CpG
      is certainly the major contribution to the curving of the whole CRE segment in
      both the unbound and bound states. Comparison with the crystal structure of CRE
      bound to GCN4 shows that the deformation induced by the protein is concentrated
      mainly on the CpG step, rendering the bound structure of CRE closer to the
      structure of the 12-0 tetradecanoylphorbol-beta-acetate-responsive element.

PMID- 10920001
TI  - Analytical description of transmembrane voltage induced by electric fields on
      spheroidal cells.
AB  - An analytical description of transmembrane voltage induced on spherical cells was
      determined in the 1950s, and the tools for numerical assessment of transmembrane
      voltage induced on spheroidal cells were developed in the 1970s. However, it has
      often been claimed that an analytical description is unattainable for spheroidal
      cells, while others have asserted that even if attainable, it does not befit the
      reality due to the nonuniform membrane thickness, which is unrealistic but
      inevitable in spheroidal geometry. In this paper we show that for all spheroidal
      cells, membrane thickness is irrelevant to the induced transmembrane voltage
      under the assumption of a nonconductive membrane, which was also applied in the
      derivation of Schwan's equation. We then derive the analytical description of
      transmembrane voltage induced on prolate and oblate spheroidal cells. The final
      result, which we cast from spheroidal into more familiar spherical coordinates,
      represents a generalization of Schwan's equation to all spheroidal cells (of
      which spherical cells are a special case). The obtained expression is easy to
      apply, and we give a simple example of such application. We conclude the study by
      analyzing the variation of induced transmembrane voltage as a spheroidal cell is
      stretched by the field, performing one study at a constant membrane surface area,
      and another at a constant cell volume.

PMID- 10920002
TI  - Optimization of nucleic acid sequences.
AB  - Base sequence influences the structure, mechanics, dynamics, and interactions of
      nucleic acids. However, studying all possible sequences for a given fragment
      leads to a number of base combinations that increases exponentially with length.
      We present here a novel methodology based on a multi-copy approach enabling us to
      determine which base sequence favors a given structural change or interaction via
      a single energy minimization. This methodology, termed ADAPT, has been
      implemented starting from the JUMNA molecular mechanics program by adding special
      nucleotides, "lexides," containing all four bases, whose contribution to the
      energy of the system is weighted by continuously variable coefficients. We
      illustrate the application of this approach in the case of double-stranded DNA by
      determining the optimal sequences satisfying structural (B-Z transition),
      mechanical (intrinsic curvature), and interaction (ligand-binding) properties.

PMID- 10920003
TI  - Bimolecular reaction simulation using Weighted Ensemble Brownian dynamics and the
      University of Houston Brownian Dynamics program.
AB  - We discuss here the implementation of the Weighted Ensemble Brownian (WEB)
      dynamics algorithm of Huber and Kim in the University of Houston Brownian
      Dynamics (UHBD) suite of programs and its application to bimolecular association
      problems. WEB dynamics is a biased Brownian dynamics (BD) algorithm that is more
      efficient than the standard Northrup-Allison-McCammon (NAM) method in cases where
      reaction events are infrequent because of intervening free energy barriers. Test
      cases reported here include the Smoluchowski rate for association of spheres, the
      association of the enzyme copper-zinc superoxide dismutase with superoxide anion,
      and the binding of the superpotent sweetener N-(p-cyanophenyl)-N'
      (diphenylmethyl)-guanidinium acetic acid to a monoclonal antibody fragment,
      NC6.8. Our results show that the WEB dynamics algorithm is a superior simulation
      method for enzyme-substrate reaction encounters with large free energy barriers.

PMID- 10920004
TI  - Sialyl Lewis(x)-mediated, PSGL-1-independent rolling adhesion on P-selectin.
AB  - Selectin-mediated cell adhesion is an essential component of the inflammatory
      response. In an attempt to unambiguously identify molecular features of ligands
      that are necessary to support rolling adhesion on P-selectin, we have used a
      reconstituted ("cell-free") system in which ligand-coated beads are perfused over
      soluble P-selectin surfaces. We find that beads coated with the saccharides
      sialyl Lewis(x) (sLe(x)), sialyl Lewis(a) (sLe(a)), and sulfated Lewis(x)
      (HSO(3)Le(x) support rolling adhesion on P-selectin surfaces. Although it has
      been suggested that glycosylation and sulfation of P-selectin glycoprotein ligand
      1 (PSGL-1) is required for high-affinity binding and rolling on P-selectin, our
      findings indicate that sulfation of N-terminal tyrosine residues is not required
      for binding or rolling. However, beads coated with a tyrosine-sulfated, sLe(x)
      modified, PSGL-1-Fc chimera support slower rolling on P-selectin than beads
      coated with sLe(x) alone, suggesting that sulfation improves rolling adhesion by
      modulating binding to P-selectin. In addition, we find it is not necessary that P
      selectin carbohydrate ligands be multivalent for robust rolling to occur. Our
      results demonstrate that beads coated with monovalent sLe(x), exhibiting a more
      sparse distribution of carbohydrate than a similar amount of the multivalent
      form, are sufficient to yield rolling adhesion. The relative abilities of various
      ligands to support rolling on P-selectin are quantitatively examined among
      themselves and in comparison to human neutrophils. Using stop-time distributions,
      rolling dynamics at video frame rate resolution, and the average and variance of
      the rolling velocity, we find that P-selectin ligands display the following
      quantitative trend, in order of decreasing ability to support rolling adhesion on
      P-selectin: PSGL-1-Fc > sLe(a) approximately sLe(x) > HSO(3)Le(x).

PMID- 10920005
TI  - A micromechanic study of cell polarity and plasma membrane cell body coupling in
      Dictyostelium.
AB  - We used micropipettes to aspirate leading and trailing edges of wild-type and
      mutant cells of Dictyostelium discoideum. Mutants were lacking either myosin II
      or talin, or both proteins simultaneously. Talin is a plasma membrane-associated
      protein important for the coupling between membrane and actin cortex, whereas
      myosin II is a cytoplasmic motor protein essential for the locomotion of
      Dictyostelium cells. Aspiration into the pipette occurred above a threshold
      pressure only. For all cells containing talin this threshold was significantly
      lower at the leading edge of an advancing cell as compared to its rear end,
      whereas we found no such difference in cells lacking talin. Wild-type and talin
      deficient cells were able to retract from the pipette against an applied suction
      pressure. In these cells, retraction was preceded by an accumulation of myosin II
      in the tip of the aspirated cell lobe. Mutants lacking myosin II could not
      retract, even if the suction pressures were removed after aspiration. We
      interpreted the initial instability and the subsequent plastic deformation of the
      cell surface during aspiration in terms of a fracture between the cell plasma
      membrane and the cell body, which may involve destruction of part of the cortex.
      Models are presented that characterize the coupling strength between membrane and
      cell body by a surface energy sigma. We find sigma approximately 0.6(1.6) mJ/m(2)
      at the leading (trailing) edge of wild-type cells.

PMID- 10920006
TI  - Magnetic phagosome motion in J774A.1 macrophages: influence of cytoskeletal
      drugs.
AB  - The role of the different cytoskeletal structures like microfilaments (MF),
      microtubuli (MT), and intermediate filaments (IF) in phagosome motion is unclear.
      These cytoskeletal units play an important role in macrophage function
      (migration, phagocytosis, phagosome transport). We investigated ferromagnetic
      phagosome motions by cell magnetometry. J774A.1 macrophages were incubated with
      1.3-microm spherical magnetite particles for 24 h, after which more than 90% of
      the particles had been phagocytized. Phagosome motions can be caused either by
      the cell itself (relaxation) or by applying magnetic twisting forces, yielding
      cell stiffness and viscoelastic properties of the cytoskeleton. Apparent
      viscosity of the cytoplasm was non-Newtonian and showed a shear-rate-dependent
      power law behavior. Elastically stored energy does not force the magnetic
      phagosomes back to their initial orientation: 57% of the twisting shear was not
      recoverable. Cytoskeletal drugs, like Cytochalasin D (CyD, 2 - 4 microM),
      Colchicine (CoL, 10 microM), or Acrylamide (AcL, 40 mM) were added in order to
      disturb the different cytoskeletal structures. AcL disintegrates IF, but affected
      neither stochastic (relaxation) nor directed phagosome motions. CyD disrupts MF,
      resulting in a retarded stochastic phagosome motion (relative decay 0.53 +/- 0.01
      after 5 min versus 0.34 +/- 0.01 in control), whereas phagosome twisting shows
      only a small response with a 9% increase of stiffness and a small reduction of
      recoverable strain. CoL depolymerizes the MT, inducing a moderately accelerated
      relaxation (relative decay 0.28 +/- 0.01 after 5 min) and a 10% increase of cell
      stiffness, where the pure viscous shear is increased and the viscoelastic recoil
      is inhibited by 40%. Combining the two drugs conserves both effects. After
      disintegrating either MF or MT, phagosome motion and cytoskeletal stiffness
      reflect the behavior of either MT or MF, respectively. The results verify that
      the dominant phagosome transport mechanism is MF-associated. MT depolymerization
      by CoL induces an activation of the F-actin synthesis, which may induce an
      accelerated relaxation and an increase of stiffness. Cell mechanical properties
      are not modulated by MF depolymerization, whereas MT depolymerization causes a
      loss of viscous resistance and a loss of cell elasticity. The mean energy for
      stochastic phagosome transport is 5*10(-18) Joules and corresponds to a force of
      7 pN on a single 1.3-microm phagosome.

PMID- 10920007
TI  - Calcium channel beta subunit promotes voltage-dependent modulation of alpha 1 B
      by G beta gamma.
AB  - Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore
      forming alpha1 subunit and auxiliary subunits, including the intracellular beta
      subunit, which has a strong influence on the channel properties. Voltage
      dependent inhibitory modulation of neuronal VDCCs occurs primarily by activation
      of G-proteins and elevation of the free G beta gamma dimer concentration. Here we
      have examined the interaction between the regulation of N-type (alpha 1 B)
      channels by their beta subunits and by G beta gamma dimers, heterologously
      expressed in COS-7 cells. In contrast to previous studies suggesting antagonism
      of G protein inhibition by the VDCC beta subunit, we found a significantly larger
      G beta gamma-dependent inhibition of alpha 1 B channel activation when the VDCC
      alpha 1 B and beta subunits were coexpressed. In the absence of coexpressed VDCC
      beta subunit, the G beta gamma dimers, either expressed tonically or elevated via
      receptor activation, did not produce the expected features of voltage-dependent G
      protein modulation of N-type channels, including slowed activation and prepulse
      facilitation, while VDCC beta subunit coexpression restored all of the hallmarks
      of G beta gamma modulation. These results suggest that the VDCC beta subunit must
      be present for G beta gamma to induce voltage-dependent modulation of N-type
      calcium channels.

PMID- 10920008
TI  - Secondary structure components and properties of the melibiose permease from
      Escherichia coli: a fourier transform infrared spectroscopy analysis.
AB  - The structure of the melibiose permease from Escherichia coli has been
      investigated by Fourier transform infrared spectroscopy, using the purified
      transporter either in the solubilized state or reconstituted in E. coli lipids.
      In both instances, the spectra suggest that the permease secondary structure is
      dominated by alpha-helical components (up to 50%) and contains beta-structure
      (20%) and additional components assigned to turns, 3(10) helix, and nonordered
      structures (30%). Two distinct and strong absorption bands are recorded at 1660
      and 1653 cm(-1), i.e., in the usual range of absorption of helices of membrane
      proteins. Moreover, conditions that preserve the transporter functionality
      (reconstitution in liposomes or solubilization with dodecyl maltoside) make
      possible the detection of two separate alpha-helical bands of comparable
      intensity. In contrast, a single intense band, centered at approximately 1656 cm(
      1), is recorded from the inactive permease in Triton X-100, or a merged and
      broader signal is recorded after the solubilized protein is heated in dodecyl
      maltoside. It is suggested that in the functional permease, distinct signals at
      1660 and 1653 cm(-1) arise from two different populations of alpha-helical
      domains. Furthermore, the sodium- and/or melibiose-induced changes in amide I
      line shape, and in particular, in the relative amplitudes of the 1660 and 1653
      cm(-1) bands, indicate that the secondary structure is modified during the early
      step of sugar transport. Finally, the observation that approximately 80% of the
      backbone amide protons can be exchanged suggests high conformational flexibility
      and/or a large accessibility of the membrane domains to the aqueous solvent.

PMID- 10920009
TI  - Rotational mobility and orientational stability of a transport protein in lipid
      membranes.
AB  - A single-cysteine mutant of the lactose transport protein LacS(C320A/W399C) from
      Streptococcus thermophilus was selectively labeled with a nitroxide spin label,
      and its mobility in lipid membranes was studied as a function of its
      concentration in the membrane by saturation-transfer electron spin resonance.
      Bovine rhodopsin was also selectively spin-labeled and studied to aid the
      interpretation of the measurements. Observations of spin-labeled proteins in
      macroscopically aligned bilayers indicated that the spin label tends to orient so
      as to reflect the transmembrane orientation of the protein. Rotational
      correlation times of 1-2 micros for purified spin-labeled bovine rhodopsin in
      lipid membranes led to viscosities of 2.2 poise for bilayers of
      dimyristoylphosphatidylcholine (28 degrees C) and 3.0 poise for the specific
      mixture of lipids used to reconstitute LacS (30 degrees C). The rotational
      correlation time for LacS did not vary significantly over the range of low
      concentrations in lipid bilayers, where optimal activity was seen to decrease
      sharply and was determined to be 9 +/- 1 micros (mean +/- SD) for these samples.
      This mobility was interpreted as being too low for a monomer but could correspond
      to a dimer if the protein self-associates into an elongated configuration within
      the membrane. Rather than changing its oligomeric state, LacS appeared to become
      less ordered at the concentrations in aligned membranes exceeding 1:100 (w/w)
      with respect to the lipid.

PMID- 10920010
TI  - Transmembrane domain of M2 protein from influenza A virus studied by solid-state
      (15)N polarization inversion spin exchange at magic angle NMR.
AB  - The M2 protein from the influenza A virus forms a proton channel in the virion
      that is essential for infection. This tetrameric protein appears to form a four
      helix bundle spanning the viral membrane. Here the solid-state NMR method, 2D
      polarization inversion spin exchange at magic angle (PISEMA), has been used to
      obtain multiple constraints from specifically amino acid-labeled samples. The
      improvement of spectral resolution from 2D PISEMA over 1D methods and 2D
      separated local field methods is substantial. The reliability of the method is
      validated by comparison of anisotropic chemical shift and heteronuclear dipolar
      interactions from single site labeled samples. The quantitative interpretation of
      the high-resolution constraints confirms the helix tilt to be within the range of
      previous experimental determinations (32 degrees -38 degrees ). The binding of
      the channel inhibitor, amantadine, results in no change in the backbone structure
      at position Val(27,28), which is thought to be a potential binding site for the
      inhibitor.

PMID- 10920011
TI  - Mechanisms of maurotoxin action on Shaker potassium channels.
AB  - Maurotoxin (alpha-KTx6.2) is a toxin derived from the Tunisian chactoid scorpion
      Scorpio maurus palmatus, and it is a member of a new family of toxins that
      contain four disulfide bridges (, Eur. J. Biochem. 254:468-479). We investigated
      the mechanism of the maurotoxin action on voltage-gated K(+) channels expressed
      in Xenopus oocytes. Maurotoxin blocks the channels in a voltage-dependent manner,
      with its efficacy increasing with greater hyperpolarization. We show that an
      amino acid residue in the external mouth of the channel pore segment that is
      known to be involved in the actions of other peptide toxins is also involved in
      maurotoxin's interaction with the channel. We conclude that, despite the unusual
      disulfide bridge pattern, the mechanism of the maurotoxin action is similar to
      those of other K(+) channel toxins with only three disulfide bridges.

PMID- 10920012
TI  - A Grand Canonical Monte Carlo-Brownian dynamics algorithm for simulating ion
      channels.
AB  - A computational algorithm based on Grand Canonical Monte Carlo (GCMC) and
      Brownian Dynamics (BD) is described to simulate the movement of ions in membrane
      channels. The proposed algorithm, GCMC/BD, allows the simulation of ion channels
      with a realistic implementation of boundary conditions of concentration and
      transmembrane potential. The method is consistent with a statistical mechanical
      formulation of the equilibrium properties of ion channels (; Biophys. J. 77:139
      153). The GCMC/BD algorithm is illustrated with simulations of simple test
      systems and of the OmpF porin of Escherichia coli. The approach provides a
      framework for simulating ion permeation in the context of detailed microscopic
      models.

PMID- 10920013
TI  - Replacement of glycine 232 by aspartic acid in the KdpA subunit broadens the ion
      specificity of the K(+)-translocating KdpFABC complex.
AB  - Replacement of glycine residue 232 with aspartate in the KdpA subunit of the K(+)
      translocating KdpFABC complex of Escherichia coli leads to a transport complex
      that has reduced affinity for K(+) and has lost the ability to discriminate Rb(+)
      ions (, J. Biol. Chem. 270:6678-6685). This glycine residue is the first in a
      highly conserved GGG motif that was aligned with the GYG sequence of the
      selectivity filter (P- or H5-loop) of K(+) channels (, Nature. 371:119-122).
      Investigations with the purified and reconstituted KdpFABC complex using the
      potential sensitive fluorescent dye DiSC(3)(5) and the "caged-ATP/planar bilayer
      method" confirm the altered ion specificity observed in uptake measurements with
      whole cells. In the absence of cations a transient current was observed in the
      planar bilayer measurements, a phenomenon that was previously observed with the
      wild-type enzyme and with another kdpA mutant (A:Q116R) and most likely
      represents the movement of a protein-fixed charge during a conformational
      transition. After addition of K(+) or Rb(+), a stationary current could be
      observed, representing the continuous pumping activity of the KdpFABC complex. In
      addition, DiSC(3)(5) and planar bilayer measurements indicate that the A:G232D
      Kdp-ATPase also transports Na(+), Li(+), and H(+) with a reduced rate.
      Similarities to mutations in the GYG motif of K(+) channels are discussed.

PMID- 10920014
TI  - Effects of imperatoxin A on local sarcoplasmic reticulum Ca(2+) release in frog
      skeletal muscle.
AB  - We have investigated the effects of imperatoxin A (IpTx(a)) on local calcium
      release events in permeabilized frog skeletal muscle fibers, using laser scanning
      confocal microscopy in linescan mode. IpTx(a) induced the appearance of Ca(2+)
      release events from the sarcoplasmic reticulum that are approximately 2 s and
      have a smaller amplitude (31 +/- 2%) than the "Ca(2+) sparks" normally seen in
      the absence of toxin. The frequency of occurrence of long-duration imperatoxin
      induced Ca(2+) release events increased in proportion to IpTx(a) concentrations
      ranging from 10 nM to 50 nM. The mean duration of imperatoxin-induced events in
      muscle fibers was independent of toxin concentration and agreed closely with the
      channel open time in experiments on isolated frog ryanodine receptors (RyRs)
      reconstituted in planar lipid bilayer, where IpTx(a) induced opening of single
      Ca(2+) release channels to prolonged subconductance states. These results suggest
      involvement of a single molecule of IpTx(a) in the activation of a single Ca(2+)
      release channel to produce a long-duration event. Assuming the ratio of full
      conductance to subconductance to be the same in the fibers as in bilayer, the
      amplitude of a spark relative to the long event indicates involvement of at most
      four RyR Ca(2+) release channels in the production of short-duration Ca(2+)
      sparks.

PMID- 10920015
TI  - Evidence for a role of the lumenal M3-M4 loop in skeletal muscle Ca(2+) release
      channel (ryanodine receptor) activity and conductance.
AB  - We tested the hypothesis that part of the lumenal amino acid segment between the
      two most C-terminal membrane segments of the skeletal muscle ryanodine receptor
      (RyR1) is important for channel activity and conductance. Eleven mutants were
      generated and expressed in HEK293 cells focusing on amino acid residue I4897
      homologous to the selectivity filter of K(+) channels and six other residues in
      the M3-M4 lumenal loop. Mutations of amino acids not absolutely conserved in RyRs
      and IP(3)Rs (D4903A and D4907A) showed cellular Ca(2+) release in response to
      caffeine, Ca(2+)-dependent [(3)H]ryanodine binding, and single-channel K(+) and
      Ca(2+) conductances not significantly different from wild-type RyR1. Mutants with
      an I4897 to A, L, or V or D4917 to A substitution showed a decreased single
      channel conductance, loss of high-affinity [(3)H]ryanodine binding and regulation
      by Ca(2+), and an altered caffeine-induced Ca(2+) release in intact cells. Mutant
      channels with amino acid residue substitutions that are identical in the RyR and
      IP(3)R families (D4899A, D4899R, and R4913E) exhibited a decreased K(+)
      conductance and showed a loss of high-affinity [(3)H]ryanodine binding and loss
      of single-channel pharmacology but maintained their response to caffeine in a
      cellular assay. Two mutations (G4894A and D4899N) were able to maintain
      pharmacological regulation both in intact cells and in vitro but had lower single
      channel K(+) and Ca(2+) conductances than the wild-type channel. The results
      support the hypothesis that amino acid residues in the lumenal loop region
      between the two most C-terminal membrane segments constitute a part of the ion
      conducting pore of RyR1.

PMID- 10920017
TI  - Combined allosteric and competitive interaction between extracellular Na(+) and
      K(+) during ion transport by the alpha(1), alpha(2), and alpha(3) isoforms of the
      Na, K-ATPase.
AB  - A combined allosteric and competitive model describes the interaction between
      extracellular Na(+) and Rb(+) during ion transport mediated by the Na, K-ATPase.
      The model was developed from experiments based on (86)Rb uptake by whole cells
      transfected with rat isoforms of the enzyme. In the absence of Na(+), only a
      single transport site for extracellular Rb(+) exists. After the occupation of the
      Na(+)-specific allosteric site, the Rb(+) transport pocket opens to allow
      occupation by an additional Rb(+) and the subsequent transport of the two Rb(+)
      ions into the cells. Na(+) can also directly compete with Rb(+) for binding to at
      least one of the transport sites. While the model derived here applies to each of
      the three rat isoforms of the Na, K-ATPase expressed in HeLa cells, subtle
      differences exist among the isoforms. The alpha(3)* isoform has an increased
      intrinsic affinity for Rb(+) and a lower affinity for the allosteric Na(+) site
      than alpha(1) or alpha(2)*. The stimulation of uptake observed according to the
      best-fit model is due to the displacement by Rb(+) of inhibitory Na(+) bound to
      the transport site.

PMID- 10920016
TI  - The I182 region of k(ir)6.2 is closely associated with ligand binding in K(ATP)
      channel inhibition by ATP.
AB  - The ATP-inhibited potassium (K(ATP)) channel is assembled from four inward
      rectifier potassium (K(ir)6.x) subunits and four sulfonylurea receptor (SURx)
      subunits. The inhibitory action of ATP is mediated by at least two distinct
      functional domains within the C-terminal cytoplasmic tail of K(ir)6.2. The G334D
      mutation of K(ir)6.2 virtually eliminates ATP-dependent gating with no effect on
      ligand-independent gating, suggesting a role in linkage of the site to the gate
      or in the ATP binding site, itself. The T171A mutation of K(ir)6.2 strongly
      disrupts both ATP-dependent and ligand-independent gating, suggesting a role for
      T171 in the gating step. A neighboring mutation, I182Q, virtually eliminates ATP
      inhibition, but its effect on ligand-independent gating remained unknown. We have
      now characterized both the K(i) values for inhibition by ATP and the ligand
      independent gating kinetics of 15 substitutions at position 182. All
      substitutions decreased ATP-dependent inhibition gating as measured by the K(i),
      many profoundly so, yet had little or no effect on ligand-independent gating
      kinetics. Thus, substitutions at position 182 are unlikely to act by disrupting
      inhibition gate movement. Our results indicate an indispensable role for I182 in
      a step of the ATP binding mechanism, the linkage mechanism coupling the ATP
      binding site to the inhibition gate, or both.

PMID- 10920018
TI  - Blockers of VacA provide insights into the structure of the pore.
AB  - The cytotoxic effects of the Helicobacter pylori toxin VacA, an important
      etiogenic factor in human gastric diseases, are due to its ability to form anion
      selective pores in target cell membranes. We have studied the inhibition of
      channel activity by 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and 4, 4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), representatives of two
      popular classes of chloride channel blockers, to gain information on the
      mechanism of blocking and on the unknown structure of the VacA pore. The data
      indicate that both compounds produce a fast block by binding to separate but
      mutually exclusive sites within the channel lumen. DIDS binds close to the pore
      opening on the side of protein insertion, whereas NPPB blocks at a position in
      the opposite half of the channel. Although DIDS reaches the blocking site by
      traveling along the lumen, inhibition by NPPB appears to involve mainly partition
      of the compound into the membrane, voltage-independent diffusion from it to the
      inhibitory position, and voltage-dependent exit. The data are consistent with a
      pore that can be more easily entered from the side of protein insertion than from
      the opposite end.

PMID- 10920019
TI  - Characterization of an integral protein of the brush border membrane mediating
      the transport of divalent metal ions.
AB  - The transport of Fe(2+) and other divalent transition metal ions across the
      intestinal brush border membrane (BBM) was investigated using brush border
      membrane vesicles (BBMVs) as a model. This transport is an energy-independent,
      protein-mediated process. The divalent metal ion transporter of the BBM is a
      spanning protein, very likely a protein channel, that senses the phase transition
      of the BBM, as indicated by a break in the Arrhenius plot. The transporter has a
      broad substrate range that includes Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and
      Zn(2+). Under physiological conditions the transport of divalent metal ions is
      proton-coupled, leading to the acidification of the internal cavity of BBMVs. The
      divalent metal ion transporter can be solubilized in excess detergent (30 mM
      diheptanoylphosphatidylcholine or 1% Triton X-100) and reconstituted into an
      artificial membrane system by detergent removal. The reconstituted membrane
      system showed metal ion transport characteristics similar to those of the
      original BBMVs. The properties of the protein described here closely resemble
      those of the proton-coupled divalent cation transporter (DCT1, Nramp2) described
      by, Nature. 388:482-488). We may conclude that a protein of the Nramp family is
      present in the BBM, facilitating the transport of Fe(2+) and other divalent
      transition metal ions.

PMID- 10920021
TI  - Effect of cholesterol on molecular transport of organic cations across liposome
      bilayers probed by second harmonic generation.
AB  - The effect of cholesterol on the molecular transport of an organic cation,
      malachite green (MG), across large unilamellar dioleolyphosphatidylglycerol
      (DOPG) liposome bilayers with 0-50 mol% cholesterol was studied by second
      harmonic generation (SHG). Because SHG is a surface-specific technique, it
      requires no labeled molecule, quencher, or shifting agent to distinguish the
      location of the solute molecules. An additional important feature of SHG is that
      it is sensitive only to the probe molecules bound to the liposome, whereas other
      methods can only differentiate between molecules that are outside and those
      inside the liposome. The transport kinetics of MG across the liposome bilayers
      was observed in real time, and the results show that cholesterol retards the rate
      of transport of MG across liposome bilayers. The rate was found to decrease by
      six times for 50 mol% cholesterol content compared with cholesterol-free
      liposomes. This demonstrates the applicability of SHG to investigation of the
      effect of liposome composition on the transport kinetics across the liposome
      bilayers.

PMID- 10920020
TI  - 1H and (13)C NMR of multilamellar dispersions of polyunsaturated (22:6)
      phospholipids.
AB  - The polyunsaturated fatty acid docosahexaenoic acid (DHA) makes up approximately
      50% of the lipid chains in the retinal rod outer segment disk membranes and a
      large fraction of the lipid chains in the membranes of neuronal tissues. There is
      an extensive literature concerned with the dietary requirements for essential
      fatty acids and the importance of DHA to human health, but relatively little
      research has been done on the physical properties of this important molecule.
      Using (1)H and (13)C MAS NMR measurements of dispersions of 1-palmitoyl-2
      docosahexaenoyl-phosphatidylcholine in excess phosphate buffer, we have
      unambiguously assigned most of the resonances in both the (1)H and (13)C NMR
      spectra. We were able to use cross-polarization spectroscopy to follow the
      transfer of polarization from specific (1)H nuclei not only to their directly
      bonded (13)C but also to those (13)C that are in close proximity, even though
      they are not directly bonded. Cross-peaks in two-dimensional cross-polarization
      spectra revealed a close association between the choline headgroup and at least
      part of the DHA chain but not with the palmitate chain. Finally, we examined the
      dynamics of the different parts of this lipid molecule, using rotating frame spin
      lattice relaxation measurements, and found that methylene groups of both chains
      experience important motions with correlation times in the 10-micros range, with
      those for the palmitate chain being approximately 50% longer than those of the
      DHA chain. The choline headgroup and the chain terminal groups have significantly
      shorter correlation times, and that part of the dipolar interaction that is
      fluctuating at these correlation times is significantly smaller for these groups
      than it is for the palmitate and DHA chain methylenes.

PMID- 10920022
TI  - Formation of three-dimensional protein-lipid aggregates in monolayer films
      induced by surfactant protein B.
AB  - This study focuses on the structural organization of surfactant protein B (SP-B)
      containing lipid monolayers. The artificial system is composed of the saturated
      phospholipids dipalmitoylphosphatidylcholine (DPPC) and
      dipalmitoylphosphatidylglycerol (DPPG) in a molar ratio of 4:1 with 0.2 mol% SP
      B. The different "squeeze-out" structures of SP-B were visualized by scanning
      probe microscopy and compared with structures formed by SP-C. Particularly, the
      morphology and material properties of mixed monolayers containing 0.2 mol% SP-B
      in a wide pressure range of 10 to 54 mN/m were investigated revealing that
      filamentous domain boundaries occur at intermediate surface pressure (15-30
      mN/m), while disc-like protrusions prevail at elevated pressure (50-54 mN/m). In
      contrast, SP-C containing lipid monolayers exhibit large flat protrusions
      composed of stacked bilayers in the plateau region (app. 52 mN/m) of the pressure
      area isotherm. By using different scanning probe techniques (lateral force
      microscopy, force modulation, phase imaging) it was shown that SP-B is dissolved
      in the liquid expanded rather than in the liquid condensed phase of the
      monolayer. Although artificial, the investigation of this system contributes to
      further understanding of the function of lung surfactant in the alveolus.

PMID- 10920023
TI  - Fluorescence-based evaluation of the partitioning of lipids and lipidated
      peptides into liquid-ordered lipid microdomains: a model for molecular
      partitioning into "lipid rafts".
AB  - A fluorescence-quenching assay is described that can directly monitor the
      relative extents of partitioning of different but structurally homologous
      fluorescent molecules into liquid-ordered (l(o)) domains in lipid vesicles
      exhibiting liquid-ordered/liquid-disordered (l(o)/l(d)) phase coexistence.
      Applying this assay to a series of bimane-labeled diacyl phospholipid probes in
      cholesterol-containing ternary lipid mixtures exhibiting l(o)/l(d) phase
      separation, we demonstrate that partitioning into l(o)-phase domains is
      negligible for diunsaturated species and greatest for long-chain disaturated
      species. These conclusions agree well with those derived from previous studies of
      the association of lipids and lipid-anchored molecules with l(o)-phase domains,
      using methods based on the isolation of a detergent-insoluble fraction from model
      or biological membranes at low temperatures. However, we also find that
      monounsaturated and shorter-chain saturated species partition into l(o) phases
      with significant, albeit modest affinities, and that the level of partitioning of
      these latter species into l(o)-phase domains is significantly underestimated
      (relative to that of their long-chain saturated counterparts) by the criterion of
      low-temperature detergent insolubility. Finally, applying the fluorescence
      quenching method to a family of lipid-modified peptides, we demonstrate that the
      S-palmitoyl/S-isoprenyl dual-lipidation motif found in proteins such as H- and N
      ras and yeast Ste18p does not promote significant association with l(o) domains
      in l(o)/l(d)-phase-separated bilayers.

PMID- 10920024
TI  - Displacement currents associated with the insertion of Alzheimer disease amyloid
      beta-peptide into planar bilayer membranes.
AB  - The role of endogenous amyloid beta-peptides as causal factors of
      neurodegenerative diseases is largely unknown. We have previously reported that
      interactions between Alzheimer's disease A beta P[1-40] peptide in solution and
      planar bilayer membranes made from anionic phospholipids lead to the formation of
      cation-selective channels. We now find and report here that the spontaneous
      insertion of free A beta P[1-40] across the bilayer can be detected as an
      increase in bilayer capacity. To this end we recorded the displacement currents
      across planar bilayers (50 mM KCl on both sides) in response to sudden
      displacements of the membrane potential, from -300 to 300 mV in 20-mV increments.
      To monitor the A beta P[1-40]-specific displacement currents, we added A beta P[1
      40] (1-5 microM) to the solution on either side of the membrane and noted that
      the direction of the displacement current depended on the side with A beta P[1
      40]. The size of the A beta P[1-40]-specific charge displaced during a pulse was
      always equal to the charge returning to the original configuration after the
      pulse, suggesting that the dipole molecules are confined to the membrane. As a
      rule, the steady-state distribution of the A beta P[1-40]-specific charges within
      the bilayer could be fit by a Boltzmann distribution. The potential at which the
      charges were found to be equally distributed (V(o)) were approximately -135 mV
      (peptide added to the solution in the compartment electrically connected to
      earth) and 135 mV (peptide added to the solution connected to the input of the
      amplifier). The A beta P[1-40]-specific transfer of charge reached a maximum
      value (Q(max)) when the electrical potential of the side containing the amyloid
      beta-protein was taken to either -300 or 300 mV. For a circular membrane of 25
      microm radius ( approximately 2000 microm(2)), the total A beta P[1-40]-specific
      charge Q(max) was estimated as 55 fC, corresponding to some 170 e.c./microm(2).
      Regardless of the side selected for the addition of A beta P[1-40], at V(o) the
      charge displaced underwent an e-fold change for a approximately 27-mV change in
      potential. The effective valence (a) of the A beta P[1-40] dipole (i.e., the
      actual valence Z multiplied by the fraction of the electric field chi acting on
      the dipole) varied from 1 to 2 electronic charges. We also tested, with negative
      results, the amyloid peptide with the reverse sequence (A beta P[40-1]). These
      data demonstrate that A beta P[1-40] molecules can span the low dielectric domain
      of the bilayer, exposing charged residues (D(1), E(3), R(5), H(6), D(7), E(11),
      H(13), and H(14)) to the electric field. Thus the A beta P[1-40] molecules in
      solution must spontaneously acquire suitable conformations (beta-pleated sheet)
      allowing specific interactions with charged phospholipids. Interestingly, the
      domain from residues 676 to 704 in the APP(751) is homologous with the consensus
      sequence for lipid binding found in other membrane proteins regulated by anionic
      phospholipids.

PMID- 10920025
TI  - ATP consumption and efficiency of human single muscle fibers with different
      myosin isoform composition.
AB  - Chemomechanical transduction was studied in single fibers isolated from human
      skeletal muscle containing different myosin isoforms. Permeabilized fibers were
      activated by laser-pulse photolytic release of 1.5 mM ATP from p(3)-1-(2
      nitrophenyl)ethylester of ATP. The ATP hydrolysis rate in the muscle fibers was
      determined with a fluorescently labeled phosphate-binding protein. The effects of
      varying load and shortening velocity during contraction were investigated. The
      myosin isoform composition was determined in each fiber by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. At 12 degrees C large variations (three- to
      fourfold) were found between slow and fast (2A and 2A-2B) fibers in their maximum
      shortening velocity, peak power output, velocity at which peak power is produced,
      isometric ATPase activity, and tension cost. Isometric tension was similar in all
      fiber groups. The ATP consumption rate increased during shortening in proportion
      to shortening velocity. At 12 degrees C the maximum efficiency was similar (0.21
      0.27) for all fiber types and was reached at a higher speed of shortening for the
      faster fibers. In all fibers, peak efficiency increased to approximately 0.4 when
      the temperature was raised from 12 degrees C to 20 degrees C. The results were
      simulated with a kinetic scheme describing the ATPase cycle, in which the rate
      constant controlling ADP release is sensitive to the load on the muscle. The main
      difference between slow and fast fibers was reproduced by increasing the rate
      constant for the hydrolysis step, which was rate limiting at low loads.
      Simulation of the effect of increasing temperature required an increase in the
      force per cross-bridge and an acceleration of the rate constants in the reaction
      pathway.

PMID- 10920027
TI  - Immobilization of nucleic acids at solid surfaces: effect of oligonucleotide
      length on layer assembly.
AB  - This report investigates the effect of DNA length and the presence of an
      anchoring group on the assembly of presynthesized oligonucleotides at a gold
      surface. The work seeks to advance fundamental insight into issues that impact
      the structure and behavior of surface-immobilized DNA layers, as in, for
      instance, DNA microarray and biosensor devices. The present study contrasts
      immobilization of single-stranded DNA (ssDNA) containing a terminal, 5'
      hexanethiol anchoring group with that of unfunctionalized oligonucleotides for
      lengths from 8 to 48 bases. Qualitatively, the results indicate that the thiol
      anchoring group strongly enhances oligonucleotide immobilization, but that the
      enhancement is reduced for longer strand lengths. Interestingly, examination of
      the probe coverage as a function of strand length suggests that adsorbed thiol
      ssDNA oligonucleotides shorter than 24 bases tend to organize in end-tethered,
      highly extended configurations for which the long-term surface coverage is
      largely independent of oligonucleotide length. For strands longer than 24 bases,
      the surface coverage begins to decrease notably with probe length. The decrease
      is consistent with a less ordered arrangement of the DNA chains, presumably
      reflecting increasingly polymeric behavior.

PMID- 10920026
TI  - Characterization of single actomyosin rigor bonds: load dependence of lifetime
      and mechanical properties.
AB  - Load dependence of the lifetime of the rigor bonds formed between a single myosin
      molecule (either heavy meromyosin, HMM, or myosin subfragment-1, S1) and actin
      filament was examined in the absence of nucleotide by pulling the barbed end of
      the actin filament with optical tweezers. For S1, the relationship between the
      lifetime (tau) and the externally imposed load (F) at absolute temperature T
      could be expressed as tau(F) = tau(0).exp(-F.d/k(B)T) with tau(0) of 67 s and an
      apparent interaction distance d of 2.4 nm (k(B) is the Boltzmann constant). The
      relationship for HMM was expressed by the sum of two exponentials, with two sets
      of tau(0) and d being, respectively, 62 s and 2.7 nm, and 950 s and 1.4 nm. The
      fast component of HMM coincides with tau(F) for S1, suggesting that the fast
      component corresponds to single-headed binding and the slow component to double
      headed binding. These large interaction distances, which may be a common
      characteristic of motor proteins, are attributed to the geometry for applying an
      external load. The pulling experiment has also allowed direct estimation of the
      number of myosin molecules interacting with an actin filament. Actin filaments
      tethered to a single HMM molecule underwent extensive rotational Brownian motion,
      indicating a low torsional stiffness for HMM. From these results, we discuss the
      characteristics of interaction between actin and myosin, with the focus on the
      manner of binding of myosin.

PMID- 10920028
TI  - A study on the mechanism of the proton transport in bacteriorhodopsin: the
      importance of the water molecule.
AB  - The mechanism of proton transport around the Schiff base in bacteriorhodopsin was
      investigated by ab initio molecular orbital (MO) calculations. Computations were
      performed for the case where there is a water molecule between the Schiff base
      and the Asp residue and for the case where there is no water molecule. Changes in
      the atomic configuration and potential energy through the proton transport
      process were compared between two cases. In the absence of water, the protonated
      Schiff base was not stable, and a proton was spontaneously detached from the
      Schiff base. On the other hand, a stable structure of the protonated Schiff base
      was obtained in the presence of water. This suggests that the presence of a water
      molecule is required for stability in the formation of a protonated Schiff base.

PMID- 10920029
TI  - Decay kinetics and quantum yields of fluorescence in photosystem I from
      Synechococcus elongatus with P700 in the reduced and oxidized state: are the
      kinetics of excited state decay trap-limited or transfer-limited?
AB  - Transfer and trapping of excitation energy in photosystem I (PS I) trimers
      isolated from Synechococcus elongatus have been studied by an approach combining
      fluorescence induction experiments with picosecond time-resolved fluorescence
      measurements, both at room temperature (RT) and at low temperature (5 K). Special
      attention was paid to the influence of the oxidation state of the primary
      electron donor P700. A fluorescence induction effect has been observed, showing a
      approximately 12% increase in fluorescence quantum yield upon P700 oxidation at
      RT, whereas at temperatures below 160 K oxidation of P700 leads to a decrease in
      fluorescence quantum yield ( approximately 50% at 5 K). The fluorescence quantum
      yield for open PS I (with P700 reduced) at 5 K is increased by approximately 20
      fold and that for closed PS I (with P700 oxidized) is increased by approximately
      10-fold, as compared to RT. Picosecond fluorescence decay kinetics at RT reveal a
      difference in lifetime of the main decay component: 34 +/- 1 ps for open PS I and
      37 +/- 1 ps for closed PS I. At 5 K the fluorescence yield is mainly associated
      with long-lived components (lifetimes of 401 ps and 1.5 ns in closed PS I and of
      377 ps, 1.3 ns, and 4.1 ns in samples containing approximately 50% open and 50%
      closed PS I). The spectra associated with energy transfer and the steady-state
      emission spectra suggest that the excitation energy is not completely thermally
      equilibrated over the core-antenna-RC complex before being trapped. Structure
      based modeling indicates that the so-called red antenna pigments (A708 and A720,
      i.e., those with absorption maxima at 708 nm and 720 nm, respectively) play a
      decisive role in the observed fluorescence kinetics. The A720 are preferentially
      located at the periphery of the PS I core-antenna-RC complex; the A708 must
      essentially connect the A720 to the reaction center. The excited-state decay
      kinetics turn out to be neither purely trap limited nor purely transfer (to the
      trap) limited, but seem to be rather balanced.

PMID- 10920031
TI  - Nonideality and the nucleation of sickle hemoglobin.
AB  - The homogeneous and heterogeneous nucleation kinetics of sickle hemoglobin (HbS)
      have been studied for various degrees of solution crowding by substitution of
      cross-linked hemoglobin A, amounting to 50% of the total hemoglobin. By cross
      linking hemoglobin A, hybrid formation between hemoglobin A and hemoglobin S was
      prevented, thus simplifying the analysis of the results. Polymerization was
      induced by laser photolysis, and homogeneous nucleation kinetics were determined
      by observation of the stochastic behavior of the onset of light scattering.
      Heterogeneous nucleation was determined by observing the exponential growth of
      the progress curves, monitored by light scattering. At concentrations between 4
      and 5 mM tetramer (i.e., approximately 30 g/dl), the substitution of 50% HbA for
      HbS slows the reaction by a factor of 10(3) to 10(4). Using scaled particle
      theory to account for the crowding of HbA, the observed decrease in the
      homogeneous nucleation rate was accurately predicted, with no variation of
      parameters required. Heterogeneous nucleation, on the other hand, is not well
      described in the present formulation, and the theory for this process appears to
      require modification of the way in which nonideality is introduced. Nonetheless,
      the accuracy of the homogeneous nucleation description suggests that such an
      approach may be useful for other assembly processes that occur in a crowded
      intracellular milieu.

PMID- 10920030
TI  - Sodium dodecyl sulfate-resistant complexes of Alzheimer's amyloid beta-peptide
      with the N-terminal, receptor binding domain of apolipoprotein E.
AB  - Immunocytochemical, biochemical, and molecular genetic studies indicate that
      apolipoprotein E (apoE) plays an important role in the process of amyloidogenesis
      beta. However, there is still no clear translation of these data into the
      pathogenesis of amyloidosis-beta. Previous studies demonstrated sodium dodecyl
      sulfate (SDS)-resistant binding of apoE to the main component of Alzheimer's
      amyloid-A beta and modulation of A beta aggregation by apoE in vitro. To more
      closely characterize apoE-A beta interactions, we have studied the binding of
      thrombolytic fragments of apoE3 to A beta in vitro by using SDS-polyacrylamide
      gel electrophoresis and intrinsic fluorescence quenching. Here we demonstrate
      that SDS-resistant binding of A beta is mediated by the receptor-binding, N
      terminal domain of apoE3. Under native conditions, both the N- and C-terminal
      domains of apoE3 bind A beta; however, the former does so with higher affinity.
      We propose that the modulation of A beta binding to the N-terminal domain of apoE
      is a potential therapeutic target for the treatment of amyloidosis-beta.

PMID- 10920032
TI  - Molecular dynamics of hinge-bending motion of IgG vanishing with hydrolysis by
      papain.
AB  - We have performed dielectric relaxation measurements via a time domain
      reflectometry (TDR) method to study dynamic behaviors of the segmental
      flexibility of immunoglobulin G (IgG) in aqueous solution without antigen
      binding. In general, an intermediate relaxation process due to bound water is
      observed around 100 MHz at 25 degrees C for common proteins between two
      relaxation processes due to overall rotation and reorientation of free water.
      However, the intermediate process observed around 6 MHz for IgG was due to both
      bound water and hinge-bending motion. The apparent activation energy of 33 kJ/mol
      was larger than 27 kJ/mol for only bound water, and the relaxation strength was
      about five times as large as expected for bound water. The shape of the
      relaxation curve was very broad and asymmetric. These characteristic differences
      arising from the hinge-bending motion of IgG disappeared for fragments decomposed
      from IgG hydrolyzed by papain, since the hinge-bending motion did not exist in
      this case. We have separated the relaxation processes due to hinge-bending motion
      and bound water for IgG and obtained the Fab-Fab angle of IgG as about 130
      degrees by Kirkwood's correlation parameter and the activation energy of 34
      kJ/mol for hinge-bending motion.

PMID- 10920033
TI  - Characterization and isolation of intermediates in beta-lactoglobulin heat
      aggregation at high pH.
AB  - The early stages of heat induced aggregation at 67.5 degrees C of beta
      lactoglobulin were studied by combined static light scattering and size exclusion
      chromatography. At all conditions studied (pH 8.7 without salt and pH 6.7 with or
      without 60 mM NaCl) we observe metastable heat-modified dimers, trimers, and
      tetramers. These oligomers reach a maximum in concentration at about the time
      when large aggregates (1000-4000 kg/mol) appear, after which they decline in
      concentration. By isolating the oligomers it was demonstrated that they rapidly
      form aggregates upon heating in the absence of monomeric protein, showing that
      these species are central to the aggregation process. To our knowledge this is
      the first time that intermediates in protein aggregation have been isolated. At
      all stages of aggregation the dominant oligomer was the heat-modified dimer.
      Whereas the heat-modified oligomers are formed at a higher rate at pH 8.7 than at
      pH 6.7, the opposite is the case for the formation of aggregates from the
      metastable oligomers indicating cross-linking via disulfide bridges for the
      oligomers and noncovalent interaction in the formation of the aggregates. The
      data suggest that an aggregate nucleus is formed from four oligomers. For protein
      concentrations of 10 or 20 g/l a heat-modified monomer can be observed until
      about the time when the maximum in concentration appears of the heat-modified
      dimer. The disappearance of this heat-modified monomer correlates to the
      formation of dimers (trimers and tetramers).

PMID- 10920034
TI  - Interspin distances in spin-labeled metmyoglobin variants determined by
      saturation recovery EPR.
AB  - Saturation recovery (SR) electron paramagnetic resonance was used to determine
      the distance between iron and nitroxyl for spin-labeled metmyoglobin variants in
      low-spin and high-spin states of the Fe(III). The interspin distances were
      measured by analyzing the effect of the heme iron on the spin-lattice relaxation
      rates of the nitroxyl spin label using the modified Bloembergen equation for low
      spin species, and an analogue of the Bloembergen equation for high-spin species.
      Insight simulations of the spin-labeled protein structures also were used to
      determine the interspin distances. The distances obtained by SR for high-spin and
      low-spin complexes with 15-20 A interspin distances, for low-spin CN(-) and high
      spin formate adducts at distances up to about 30 A, and results from Insight
      calculations were in good agreement. For variants with 25-30 A interspin
      distances, the distances obtained by SR for the fluoride adducts were shorter
      than observed for the CN(-) or formate adducts or predicted by Insight
      simulations. Of the heme axial ligands examined (CN(-), imidazole, F(-), and
      formate), CN(-) is the best choice for determination of iron-nitroxyl distances
      in the range of 15-30 A.

PMID- 10920035
TI  - Characterization of the oligomeric states of insulin in self-assembly and amyloid
      fibril formation by mass spectrometry.
AB  - The self-assembly and aggregation of insulin molecules has been investigated by
      means of nanoflow electrospray mass spectrometry. Hexamers of insulin containing
      predominantly two, but up to four, Zn(2+) ions were observed in the gas phase
      when solutions at pH 4.0 were examined. At pH 3.3, in the absence of Zn(2+),
      dimers and tetramers are observed. Spectra obtained from solutions of insulin at
      millimolar concentrations at pH 2.0, conditions under which insulin is known to
      aggregate in solution, showed signals from a range of higher oligomers. Clusters
      containing up to 12 molecules could be detected in the gas phase. Hydrogen
      exchange measurements show that in solution these higher oligomers are in rapid
      equilibrium with monomeric insulin. At elevated temperatures, under conditions
      where insulin rapidly forms amyloid fibrils, the concentration of soluble higher
      oligomers was found to decrease with time yielding insoluble high molecular
      weight aggregates and then fibrils. The fibrils formed were examined by electron
      microscopy and the results show that the amorphous aggregates formed initially
      are converted to twisted, unbranched fibrils containing several protofilaments.
      Fourier transform infrared spectroscopy shows that both the soluble form of
      insulin and the initial aggregates are predominantly helical, but that formation
      of beta-sheet structure occurs simultaneously with the appearance of well-defined
      fibrils.

PMID- 10920037
TI  - Probing ligand protein binding equilibria with fluorescence fluctuation
      spectroscopy.
AB  - We examine the binding of fluorescent ligands to proteins by analyzing the
      fluctuation amplitude g(0) of fluorescence fluctuation experiments. The
      normalized variance g(0) depends on the molecular brightness and the
      concentration of each species in the sample. Thus a single g(0) measurement is
      not sufficient to resolve individual species. Titration of the ligand with
      protein establishes the link between molecular brightness and concentration by
      fitting g(0) to a binding model and allows the separation of species. We first
      apply g(0) analysis to binary dye mixtures with brightness ratios of 2 and 4 to
      demonstrate the feasibility of this technique. Next we consider the influence of
      binding on the fluctuation amplitude g(0). The dissociation coefficient, the
      molecular brightness ratio, and the stochiometry of binding strongly influence
      the fluctuation amplitude. We show that proteins with a single binding site can
      be clearly differentiated from proteins with two independent binding sites. The
      binding of fluorescein-labeled digoxigenin to a high-affinity anti-digoxin
      antibody was studied experimentally. A global analysis of the fluctuation
      amplitude and the fluorescence intensity not only recovered the dissociation
      coefficient and the number of binding sites, but also revealed the molecular
      heterogeneity of the hapten-antibody complex. Two species were used to model the
      molecular heterogeneity. We confirmed the molecular heterogeneity independently
      by fluorescence lifetime experiments, which gave fractional populations and
      molecular brightness values that were virtually identical to those of the g(0)
      analysis. The identification and characterization of molecular heterogeneity have
      far-reaching consequences for many biomolecular systems. We point out the
      important role fluctuation experiments may have in this area of research.

PMID- 10920036
TI  - Site-specific tryptophan dynamics in class A amphipathic helical peptides at a
      phospholipid bilayer interface.
AB  - The amphipathic helix plays a key role in many membrane-associating peptides and
      proteins. The dynamics of helices on membrane surfaces might be of importance to
      their function. The fluorescence anisotropy decay of tryptophan is a sensitive
      indicator of local, segmental, and global dynamics within a peptide or protein.
      We describe the use of frequency domain dynamic depolarization measurements to
      determine the site-specific tryptophan dynamics of single tryptophan amphipathic
      peptides bound to a phospholipid surface. The five 18-residue peptides studied
      are based on a class A amphipathic peptide that is known to associate at the
      interface of phospholipid bilayers. The peptides contain a single tryptophan
      located at positions 2, 3, 7, 12, or 14 in the sequence. Association of the
      peptides with egg phosphatidylcholine vesicles results in complex behavior of
      both the tryptophan intensity decay and the anisotropy decay. The anisotropy
      decays were biphasic and were fitted to an associated model where each lifetime
      component in the intensity decay is associated with a particular rotational
      correlation time from the anisotropy decay. In contrast, an unassociated model
      where all components of the intensity decay share common rotational modes was
      unable to provide an adequate fit to the data. Two correlation times were
      resolved from the associated analysis: one whose contribution to the anisotropy
      decay was dependent on the exposure of the tryptophan to the aqueous phase, and
      the other whose contribution reflected the position of the tryptophan in the
      sequence. The results are compared with existing x-ray structural data and
      molecular dynamics simulations of membrane-incorporated peptides.

PMID- 10920038
TI  - Comparison of EPR-visible Cu(2+) sites in pMMO from Methylococcus capsulatus
      (Bath) and Methylomicrobium album BG8.
AB  - X-band (9.1 GHz) and S-band (3.4 GHz) electron paramagnetic resonance (EPR)
      spectra for particulate methane monooxygenase (pMMO) in whole cells from
      Methylococcus capsulatus (Bath) grown on (63)Cu and (15)N were obtained and
      compared with previously reported spectra for pMMO from Methylomicrobium album
      BG8. For both M. capsulatus (Bath) and M. album BG8, two nearly identical Cu(2+)
      EPR signals with resolved hyperfine coupling to four nitrogens are observed. The
      EPR parameters for pMMO from M. capsulatus (Bath) (g( parallel) = 2.244, A(
      parallel) = 185 G, and A(N) = 19 G for signal one; g( parallel) = 2.246, A(
      parallel) = 180 G, and A(N) = 19 G for signal two) and for pMMO from M. album BG8
      (g( parallel) = 2.243, A( parallel) = 180 G, and A(N) = 18 G for signal one; g(
      parallel) = 2. 251, A( parallel) = 180 G, and A(N) = 18 G for signal two) are
      very similar and are characteristic of type 2 Cu(2+) in a square planar or square
      pyramidal geometry. In three-pulse electron spin echo envelope modulation (ESEEM)
      data for natural-abundance samples, nitrogen quadrupolar frequencies due to the
      distant nitrogens of coordinated histidine imidazoles were observed. The
      intensities of the quadrupolar combination bands indicate that there are three or
      four coordinated imidazoles, which implies that most, if not all, of the
      coordinated nitrogens detected in the continuous wave spectra are from histidine
      imidazoles.

PMID- 10920039
TI  - Multiple-particle tracking measurements of heterogeneities in solutions of actin
      filaments and actin bundles.
AB  - One of the central functions of actin cytoskeleton is to provide the mechanical
      support required for the establishment and maintenance of cell morphology. The
      mechanical properties of actin filament assemblies are a consequence of both the
      available polymer concentration and the actin regulatory proteins that direct the
      formation of higher order structures. By monitoring the displacement of well
      dispersed microspheres via fluorescence microscopy, we probe the degree of
      spatial heterogeneity of F-actin gels and networks in vitro. We compare the
      distribution of the time-dependent mean-square displacement (MSD) of polystyrene
      microspheres imbedded in low- and high-concentration F-actin solutions, in the
      presence and absence of the F-actin-bundling protein fascin. The MSD distribution
      of a 2. 6-microM F-actin solution is symmetric and its standard deviation is
      similar to that of a homogeneous solution of glycerol of similar zero-shear
      viscosity. However, increasing actin concentration renders the MSD distribution
      wide and asymmetric, an effect enhanced by fascin. Quantitative changes in the
      shape of the MSD distribution correlate qualitatively with the presence of large
      heterogeneities in F-actin solutions produced by increased filament concentration
      and the presence of actin bundles, as detected by confocal microscopy. Multiple
      particle tracking offers a new, quantitative method to characterize the
      organization of biopolymers in solution.

PMID- 10920040
TI  - Atomic force microscope image contrast mechanisms on supported lipid bilayers.
AB  - This work presents a methodology to measure and quantitatively interpret force
      curves on supported lipid bilayers in water. We then use this method to correlate
      topographic imaging contrast in atomic force microscopy (AFM) images of phase
      separated Langmuir-Blodgett bilayers with imaging load. Force curves collected on
      pure monolayers of both distearoylphosphatidylethanolamine (DSPE) and
      monogalactosylethanolamine (MGDG) and dioleoylethanolamine (DOPE) deposited at
      similar surface pressures onto a monolayer of DSPE show an abrupt breakthrough
      event at a repeatable, material-dependent force. The breakthrough force for DSPE
      and MGDG is sizable, whereas the breakthrough force for DOPE is too small to
      measure accurately. Contact-mode AFM images on 1:1 mixed monolayers of DSPE/DOPE
      and MGDG/DOPE have a high topographic contrast at loads between the breakthrough
      force of each phase, and a low topographic contrast at loads above the
      breakthrough force of both phases. Frictional contrast is inverted and magnified
      at loads above the breakthrough force of both phases. These results emphasize the
      important role that surface forces and mechanics can play in imaging
      multicomponent biomembranes with AFM.

PMID- 10920041
TI  - High critical temperature above T(g) may contribute to the stability of
      biological systems.
AB  - In this study, we characterized the molecular mobility around T(g) in sugars,
      poly-L-lysine and dry desiccation-tolerant biological systems, using ST-EPR, (1)H
      NMR, and FTIR spectroscopy, to understand the nature and composition of
      biological glasses. Two distinct changes in the temperature dependence of the
      rotational correlation time (tau(R)) of the spin probe 3-carboxy-proxyl or the
      second moment (M(2)) were measured in sugars and poly-L-lysine. With heating, the
      first change was associated with the melting of the glassy state (T(g)). The
      second change (T(c)), at which tau(R) abruptly decreased over several orders of
      magnitude, was found to correspond with the so-called cross-over temperature,
      where the dynamics changed from solid-like to liquid-like. The temperature
      interval between T(g) and T(c) increased in the order of sucrose < trehalose <
      raffinose </= staychose < poly-L-lysine < biological tissues, from 17 to >50
      degrees C, implying that the stability above T(g) improved in the same order.
      These differences in temperature-dependent mobilities above T(g) suggest that
      proteins rather than sugars play an important role in the intracellular glass
      formation. The exceptionally high T(c) of intracellular glasses is expected to
      provide excellent long-term stability to dry organisms, maintaining a slow
      molecular motion in the cytoplasm even at temperatures far above T(g).

PMID- 10920042
TI  - Sensitivity enhancement in fluorescence correlation spectroscopy of multiple
      species using time-gated detection.
AB  - Fluorescence correlation spectroscopy (FCS) is a powerful technique to measure
      chemical reaction rates and diffusion coefficients of molecules in thermal
      equilibrium. The capabilities of FCS can be enhanced by measuring the energy,
      polarization, or delay time between absorption and emission of the collected
      fluorescence photons in addition to their arrival times. This information can be
      used to change the relative intensities of multiple fluorescent species in FCS
      measurements and, thus, the amplitude of the intensity autocorrelation function.
      Here we demonstrate this strategy using lifetime gating in FCS experiments. Using
      pulsed laser excitation and laser-synchronized gating in the detection channel,
      we suppress photons emitted within a certain time interval after excitation.
      Three applications of the gating technique are presented: suppression of
      background fluorescence, simplification of FCS reaction studies, and
      investigation of lifetime heterogeneity of fluorescently labeled biomolecules.
      The usefulness of this technique for measuring forward and backward rates of
      protein fluctuations in equilibrium and for distinguishing between static and
      dynamic heterogeneity makes it a promising tool in the investigation of chemical
      reactions and conformational fluctuations in biomolecules.

PMID- 10920043
TI  - New insight into cellulose structure by atomic force microscopy shows the
      i(alpha) crystal phase at near-atomic resolution.
AB  - The organization of the surface of cellulose is important in cell structure, as
      well as in industrial processing and modification. Using atomic force microscopy,
      we show that the I(alpha) phase of native cellulose first proposed in 1984 and
      subsequently characterized by a triclinic unit cell exists over large areas of
      the surface of microcrystals from Valonia, one of the most highly crystalline
      celluloses. There is startling agreement between the observed structure and
      crystal models, and it is possible to identify the specific crystal face being
      imaged. The near-atomic resolution images also offer an insight into structural
      reconstructions at the surface compared to the interior. We are able to assign
      features in the images to particular side groups attached to the glucose ring and
      find indications of subtle modifications of the position of surface hydroxyls due
      to changes in hydrogen bonding.

PMID- 10920044
TI  - Chain-selective isotopic labeling for NMR studies of large multimeric proteins:
      application to hemoglobin.
AB  - Multidimensional, multinuclear NMR has the potential to elucidate the mechanisms
      of allostery and cooperativity in multimeric proteins under near-physiological
      conditions. However, NMR studies of proteins made up of non-equivalent subunits
      face the problem of severe resonance overlap, which can prevent the unambiguous
      assignment of resonances, a necessary step in interpreting the spectra. We report
      the application of a chain-selective labeling technique, in which one type of
      subunit is labeled at a time, to carbonmonoxy-hemoglobin A (HbCO A). This
      labeling method can be used to extend previous resonance assignments of key amino
      acid residues, which are important to the physiological function of hemoglobin.
      Among these amino acid residues are the surface histidyls, which account for the
      majority of the Bohr effect. In the present work, we report the results of two
      dimensional heteronuclear multiple quantum coherence (HMQC) experiments performed
      on recombinant (15)N-labeled HbCO A. In addition to the C2-proton (H epsilon(1))
      chemical shifts, these spectra also reveal the corresponding C4-proton (H
      delta(2)) resonances, correlated with the N epsilon(2) and N delta(1) chemical
      shifts of all 13 surface histidines per alpha beta dimer. The HMQC spectrum also
      allows the assignment of the H delta(1), H epsilon(1), and N epsilon(1)
      resonances of all three tryptophan residues per alpha beta dimer in HbCO A. These
      results indicate that heteronuclear NMR, used with chain-selective isotopic
      labeling, can provide resonance assignments of key regions in large, multimeric
      proteins, suggesting an approach to elucidating the solution structure of
      hemoglobin, a protein with molecular weight 64.5 kDa.

PMID- 10920045
TI  - An integrated laser trap/flow control video microscope for the study of single
      biomolecules.
AB  - We have developed an integrated laser trap/flow control video microscope for
      mechanical manipulation of single biopolymers. The instrument is automated to
      maximize experimental throughput. A single-beam optical trap capable of trapping
      micron-scale polystyrene beads in the middle of a 200-microm-deep microchamber is
      used, making it possible to insert a micropipette inside this chamber to hold a
      second bead by suction. Together, these beads function as easily exchangeable
      surfaces between which macromolecules of interest can be attached. A computer
      controlled flow system is used to exchange the liquid in the chamber and to
      establish a flow rate with high precision. The flow and the optical trap can be
      used to exert forces on the beads, the displacements of which can be measured
      either by video microscopy or by laser deflection. To test the performance of
      this instrument, individual biotinylated DNA molecules were assembled between two
      streptavidin beads, and the DNA elasticity was characterized using both laser
      trap and flow forces. DNA extension under varying forces was measured by video
      microscopy. The combination of the flow system and video microscopy is a
      versatile design that is particularly useful for the study of systems susceptible
      to laser-induced damage. This capability was demonstrated by following the
      translocation of transcribing RNA polymerase up to 650 s.

PMID- 10920046
TI  - Stereotypical physiological properties emerge during early neuronal and glial
      lineage development in the embryonic rat neocortex.
AB  - Surface immunolabeling was used together with membrane potential and/or Ca(2+)
      indicator dyes to characterize physiological properties emerging among
      precursors, neuroglial progenitors and differentiating neurons during
      neurogenesis of embryonic rat neocortex. Cells were immunoidentified with tetanus
      toxin (TnTx), which binds to gangliosides expressed by neurons, and anti-A2B5,
      which reacts with gangliosides expressed by neuroglial progenitors.
      Microdissection of the neocortex into ventricular/subventricular zone (VZ/SVZ)
      and cortical plate/subplate (CP/SP) regions further resolved the TnTx/A2B5
      immunoidentified cells into pre- and post-migratory subpopulations. Quantitative
      immunocytochemistry revealed mainly proliferative (BrdU(+)) and immature
      (nestin(+)) elements among TnTx(-)A2B5(-) precursors and TnTx(-)A2B5(+)
      progenitors in the VZ/SVZ, and the appearance of neuron-specific antigens among
      post-mitotic TnTx(+) subpopulations of the CP/SP. Flow cytometry of acutely
      prepared cells in suspension and dual-imaging of cells in culture revealed that
      ionotropic amino acid receptors and metabotropic acetylcholine receptors closely
      paralleled the emergence of voltage-dependent Na(+) and Ca(2+) channels and Na(+)
      Ca(2+) exchange activity among TnTx(+) neuronal progenitors migrating from VZ/SVZ
      to CP/SP. During this period, TnTx(-)A2B5(-) precursors and TnTx(-)A2B5(+)
      neuroglial progenitors from VZ/SVZ predominantly exhibited Ca(2+) responses to
      ATP. Thus, stereotypical and contrasting physiologies emerge among embryonic
      cortical cells in vivo as they initially progress from proliferating precursors
      and progenitors along neuronal and glial cell lineages.

PMID- 10920047
TI  - Evidence for the transient nature of a neural system supporting goal-directed
      action.
AB  - Disruption of a neural system supporting goal-directed action gives rise to
      lapses of intention in healthy individuals and disorganized behavior in patients
      with prefrontal lesions. Evidence from behavioral studies indicates that the
      occurrence of lapses in selective attention, working memory and prospective
      memory tasks is transient in nature. In the current study, we used event-related
      brain potentials to demonstrate that lapses are associated with a slow wave over
      the frontal region that begins well before stimulus onset and lasts for several
      hundred milliseconds. The magnitude of this slow wave was modulated by task
      demands, indicating that attentional processes can be flexibly allocated in the
      service of goal-directed action. Together the findings of these experiments
      indicate that lapses result from a transient inability to bring to bear the goals
      of the individual upon the action selection system.

PMID- 10920048
TI  - Convergent and complementary projections of the caudal paralaminar thalamic
      nuclei to rat temporal and insular cortex.
AB  - Thalamic nuclei adjacent to the medial geniculate body play a pivotal role in
      processing of sensory stimuli during emotional situations. These nuclei, which
      include the suprageniculate nucleus (SG), the posterior intralaminar nucleus
      (PIN), the peripeduncular nucleus (PP) and the medial division of the medial
      geniculate body (MGm), project to both cortex and amygdala, but target areas and
      the extent of the projection of individual nuclei are not known yet. The aim of
      the present study was to analyze the contribution of individual nuclei to the
      cortical projection with modern sensitive tracing techniques. Small injections of
      Miniruby or PHA-L were made into single thalamic nuclei. All thalamic nuclei have
      in common a projection into the upper portion of layer I of the temporal aspect
      of the cortical mantle. Furthermore, SG, PIN, MGm and PP each demonstrated a
      convergent projection to lower layer III and to layer IV of the ectorhinal and
      visceral cortex. Only MGm projects to layer VI of primary auditory and temporal
      association cortices. Within the perirhinal cortex zones of convergence and
      divergence exist. The present results demonstrate a differential thalamocortical
      projection of single thalamic nuclei to those cortical areas which are involved
      in the transmission of sensory signals to the amygdala via the thalamocortico
      cortical pathway and to the hippocampus via the entorhinal cortex. The thalamic
      nuclei are thus in a position to activate the amygdala and to modulate the
      information flow of the thalamocortico-cortical pathway to both amygdala and
      hippocampus.

PMID- 10920049
TI  - Visual perception of motion and 3-D structure from motion: an fMRI study.
AB  - Functional magnetic resonance imaging was used to study the cortical bases of 3-D
      structure perception from visual motion in human. Nine subjects underwent three
      experiments designed to locate the areas involved in (i) motion processing
      (random motion versus static dots), (ii) coherent motion processing (expansion/
      contraction versus random motion) and (iii) 3-D shape from motion reconstruction
      (3-D surface oscillating in depth versus random motion). Two control experiments
      tested the specific influence of speed distribution and surface curvature on the
      activation results. All stimuli consisted of random dots so that motion parallax
      was the only cue available for 3-D shape perception. As expected, random motion
      compared with static dots induced strong activity in areas V1/V2, V5+ and the
      superior occipital gyrus (SOG; presumptive V3/V3A). V1/V2 and V5+ showed no
      activity increase when comparing coherent motion (expansion or 3-D surface) with
      random motion. Conversely, V3/V3A and the dorsal parieto-occipital junction were
      highlighted in both comparisons and showed gradually increased activity for
      random motion, coherent motion and a curved surface rotating in depth, which
      suggests their involvement in the coding of 3-D shape from motion. Also, the
      ventral aspect of the left occipito-temporal junction was found to be equally
      responsive to random and coherent motion stimuli, but showed a specific
      sensitivity to curved 3-D surfaces compared with plane surfaces. As this region
      is already known to be involved in the coding of static object shape, our results
      suggest that it might integrate various cues for the perception of 3-D shape.

PMID- 10920050
TI  - Developmental history of the subplate and developing white matter in the murine
      neocortex. Neuronal organization and relationship with the main afferent systems
      at embryonic and perinatal stages.
AB  - The neuronal diversity of the subplate and developing white matter in the mouse
      was studied using a variety of neuronal markers. The subplate was first visible
      in lateral cortical areas at E13, coinciding with the emergence of the cortical
      plate. During prenatal development, this layer was formed by morphologically
      heterogeneous neurons, subsets of which were immunoreactive for GABA- and calcium
      binding proteins. From E18 onwards, a few subplate cells also contained
      neuropeptides. Colocalization experiments demonstrated that the percentages of
      neurons immunoreactive for each antigen were similar to those described in adult
      neocortex. By E15, subplate cells had received synaptic contacts. Moreover, a
      second early-neuronal population was conspicuous from E13 in the lower
      intermediate zone: the intermediate-subventricular population. Unlike subplate
      cells, these neurons were morphologically uniform, smaller and horizontally
      oriented. Nevertheless, a few of these cells also appeared within the ventricular
      zone, with a perpendicular/ oblique orientation. Most of these cells were GABA
      positive and showed calbindin immunoreactivity. At the electron microscopic
      level, no synaptic contacts were found in these neurons. Tracing studies using
      DiI showed that subplate neurons were the first to send axons outside the
      neocortex towards the ganglionic eminence at E13. At E14, subplate axons and
      ingrowing thalamic fibers met in the striate primordium. Subplate cells retained
      their projection to the thalamus during prenatal development. Thalamocortical
      axons reached the subplate at E15, and 1 day later began to invade the upper
      cortical layers. Early callosal axons, in contrast, did not run through the
      subplate to reach the contralateral hemisphere, nor did subplate cells send out
      callosal fibers. Callosal axons ran just above the subventricular zone,
      intermingled with the intermediate-subventricular neuronal population. We
      conclude that the subplate neuronal population has a chemical heterogeneity
      reminiscent of that of the adult cortex and is crucial to the establishment of
      thalamocortical relationships, whereas the intermediate-subventricular neurons
      constituted a particular GABAergic population, which includes resident cells and
      tangentially migrating postmitotic neurons spatially related to the development
      of callosal connections.

PMID- 10920051
TI  - Effects of repetitive transcranial magnetic stimulation on movement-related
      cortical activity in humans.
AB  - Several lines of evidence suggest that low-rate repetitive transcranial magnetic
      stimulation (rTMS) of the motor cortex at 1 Hz reduces the excitability of the
      motor cortex and produces metabolic changes under and at a distance from the
      stimulated side. Therefore, it has been suggested that rTMS may have beneficial
      effects on motor performance in patients with movement disorders. However, it is
      still unknown in what way these effects can be produced. The aim of the present
      study is to investigate whether rTMS of the motor cortex (15 min at 1 Hz) is able
      to modify the voluntary movement related cortical activity, as reflected in the
      Beretischaftspotential (BP), and if these changes are functionally relevant for
      the final motor performance. The cortical movement-related activity in a typical
      BP paradigm of five healthy volunteers has been recorded using 61 scalp
      electrodes, while subjects performed self-paced right thumb oppositions every 8
      20 s. After a basal recording, the BP was recorded in three different conditions,
      counterbalanced across subjects: after rTMS stimulation of the left primary motor
      area (M1) (15 min, 1 Hz, 10% above motor threshold), after 15 min of sham rTMS
      stimulation and following 15 min of voluntary movements performed with spatio
      temporal characteristics similar to those induced by TMS. The tapping test was
      used to assess motor performance before and after each condition. Only movement
      related trials with similar electromyographic (onset from muscular 'silence') and
      accelerometric patterns (same initial direction and similar amplitudes) were
      selected for computing BP waveforms. TMS- evoked and self-paced thumb movements
      had the same directional accelerometric pattern but different amplitudes. In all
      subjects, the real rTMS, but neither sham stimulation nor prolonged voluntary
      movements, produced a significant amplitude decrement of the negative slope of
      the BP; there was also a shortening of the BP onset time in four subjects. The
      effect was topographically restricted to cortical areas which were active in the
      basal condition, irrespective of the basal degree of activation at every single
      electrode. No changes in the tapping test occurred. These findings suggest that
      rTMS of the motor cortex at 1 Hz may interfere with the movement related brain
      activity, probably through influence on cortical inhibitory networks.

PMID- 10920052
TI  - Cerebral mechanisms involved in word reading in dyslexic children: a magnetic
      source imaging approach.
AB  - The purpose of the present investigation was to describe spatiotemporal brain
      activation profiles during word reading using magnetic source imaging (MSI). Ten
      right-handed dyslexic children with severe phonological decoding problems and
      eight age-matched non-impaired readers were tested in two recognition tasks, one
      involving spoken and the other printed words. Dyslexic children's activation
      profiles during the printed word recognition task consistently featured
      activation of the left basal temporal cortices followed by activation of the
      right temporoparietal areas (including the angular gyrus). Non-impaired readers
      showed predominant activation of left basal followed by left temporoparietal
      activation. In addition, we were able to rule out the hypothesis that
      hypoactivation of left temporoparietal areas in dyslexics was due to a more
      general cerebral dysfunction in these areas. Rather, it seems likely that reading
      difficulties in developmental dyslexia are associated with an aberrant pattern of
      functional connectivity between brain areas normally involved in reading, namely
      ventral visual association cortex and temporoparietal areas in the left
      hemisphere. The interindividual consistency of activation profiles characteristic
      of children with dyslexia underlines the potential utility of this technique for
      examining neurophysiological changes in response to specific educational
      intervention approaches.

PMID- 10920054
TI  - Krieg cortical kudos 2000.

PMID- 10920053
TI  - Electrophysiological evidence for fast visual processing through the human
      koniocellular pathway when stimuli move.
AB  - There is increasing evidence from cellular recordings in primates and behavioral
      studies in humans that motion can be processed by other than the magnocellular
      (M) pathway and the cortical dorsal stream. Little is known about cortical
      processing of moving stimuli when the information is conveyed by the third
      retinogeniculocortical pathway - the so-called koniocellular (K) pathway. We
      addressed this issue in humans by studying the spatio-temporal dynamics of the
      brain electrical fields evoked by tritan (S-cone isolating) and luminance-defined
      moving stimuli. Tritan and luminance stimuli are presumably carried by the K and
      M pathways respectively. We found two time intervals where significant stimulus
      specific electric fields were evoked: an early period between 40 and 75 ms after
      stimulus onset, and a later period between 175 and 240 ms. Some of these fields
      were identical for tritanand luminance-motion, suggesting that the processing of
      moving stimuli share common cortical substrates when mediated via K and M pathway
      input. However, tritan-motion stimuli also evoked unique electric fields that
      appeared earlier in time than the common motion-specific fields, indicating very
      fast activation of cortical areas specific to input through the K pathway. A
      distributed source localization procedure revealed simultaneous activation of
      striate and extrastriate areas even at the early processing stages, strongly
      suggesting a very fast activation of the visual cerebral network.

PMID- 10920056
TI  - Moderate alcohol consumption and risk of coronary heart disease among women with
      type 2 diabetes mellitus.

PMID- 10920055
TI  - What type of beta-blocker should be used to treat chronic heart failure?

PMID- 10920057
TI  - Alcohol consumption, diabetes, and coronary disease: An epidemiological
      perspective.

PMID- 10920058
TI  - Selective endothelin-A versus combined endothelin-A/endothelin-B receptor
      blockade in rat chronic heart failure.
AB  - BACKGROUND: The relative efficacy of endothelin-A (ET(A)) receptor blockade
      versus combined ET(A)-ET(B) receptor blockade in chronic heart failure (CHF) is
      still largely unknown. METHODS AND RESULTS: We compared, in a rat model of CHF
      (coronary ligation), the hemodynamic and structural effects of 1 month of
      treatment with the ET(A) antagonist ABT-627 (5 mg x kg(-1) x d(-1)), the ET(B)
      antagonist A-192621 (30 mg x kg(-1) x d(-1)) or a combination of the 2 drugs.
      Doses were chosen for their capacity to block the pressor response to ET-1 (for
      ET(A) blockade) or the depressor responses to sarafotoxin S6c or ET-1 (for ET(B)
      blockade). ET(A) and combined ET(A)-ET(B) blockade reduced systolic blood
      pressure to the same extent, whereas ET(B) blockade had no effect. In contrast,
      only combined ET(A)-ET(B) blockade significantly reduced heart rate. Both ET(A)
      and combined ET(A)-ET(B) blockade, but not ET(B) blockade alone, increased left
      ventricular (LV) fractional shortening and wall thickening and reduced LV end
      diastolic pressure, as well as LV end-diastolic and end-systolic volumes.
      However, all treatments (including ET(B) blockade) decreased LV collagen
      accumulation. CONCLUSIONS: The chronic blockade of both ET(A) and ET(B) receptors
      improved systemic hemodynamics, as well as LV function and remodeling, to the
      same extent as ET(A) receptor blockade alone. However, only combined ET(A)-ET(B)
      receptor blockade decreased heart rate. Whether this differential effect on heart
      rate affects the long-term outcome after treatment with ET(A) or mixed ET(A)
      ET(B) antagonists in CHF remains to be determined.

PMID- 10920059
TI  - Moderate alcohol consumption and risk of coronary heart disease among women with
      type 2 diabetes mellitus.
AB  - BACKGROUND: Moderate alcohol consumption is associated with reduced risk for
      coronary heart disease (CHD) in generally healthy populations. We assessed
      prospectively the association between moderate alcohol intake and CHD risk in
      women with type 2 diabetes mellitus, a group at high risk for cardiovascular
      disease. METHODS AND RESULTS: We studied women in the Nurses' Health Study who
      reported a diagnosis of diabetes mellitus at >/=30 years of age. During 39 092
      person-years of follow-up from 1980 to 1994, there were 295 CHD events documented
      among this population, including 194 cases of nonfatal myocardial infarction and
      101 cases of fatal CHD. Odds ratios derived from logistic regression were used to
      estimate relative risks (RRs) for CHD as a function of usual alcohol intake, with
      adjustment for potential confounders. Compared with diabetic women reporting no
      alcohol intake, the age-adjusted RR for nonfatal or fatal CHD among diabetic
      women reporting usual intake of 0.1 to 4.9 g (<0.5 drinks) of alcohol daily was
      0.74 (95% CI 0.56 to 0.98), and among those reporting usual intake >/=5 g/d, it
      was 0.48 (95% CI 0.32 to 0.72) (P for trend <0.0001). Inverse associations
      between alcohol intake and CHD risk remained significant in multivariate analysis
      adjusting for several other coronary risk factors (0.1 to 4. 9 g/d: RR 0.72 [95%
      CI 0.54 to 0.96]; >/=5 g/d: RR 0.45 [0.29 to 0.68]). CONCLUSIONS: Although
      potential risks of alcohol consumption must be considered, these data suggest
      that moderate alcohol consumption is associated with reduced CHD risk in women
      with diabetes and should not be routinely discouraged.

PMID- 10920060
TI  - Alcohol consumption and risk of coronary heart disease by diabetes status.
AB  - BACKGROUND: An inverse association between moderate alcohol consumption and
      coronary heart disease (CHD) has been observed in several epidemiological
      studies. To assess whether a similar association exists among diabetics, we
      examined the relation between light to moderate alcohol consumption and CHD in
      men with and without diabetes mellitus in a prospective cohort study. METHODS AND
      RESULTS: A total of 87 938 US physicians (2790 with diagnosed diabetes mellitus)
      who were invited to participate in the Physicians' Health Study and were free of
      myocardial infarction, stroke, cancer, or liver disease at baseline were followed
      for an average of 5.5 years for death with CHD as the underlying cause. During
      480 876 person-years of follow-up, 850 deaths caused by CHD were documented: 717
      deaths among nondiabetic men and 133 deaths among diabetic men. Among men without
      diabetes at baseline, the relative risk estimates for those reporting
      rarely/never, monthly, weekly, and daily alcohol consumption were 1.00
      (referent), 1.02, 0. 82, and 0.61 (95% CI 0.49 to 0.78; P for trend <0.0001)
      after adjustment for age, aspirin use, smoking, physical activity, body mass
      index, and history of angina, hypertension, and high cholesterol. Among men with
      diabetes at baseline, the relative risk estimates were 1.00 (referent), 1.11,
      0.67, and 0.42 (95% CI 0.23 to 0.77; P for trend=0.0019). CONCLUSIONS: These
      results suggest that light to moderate alcohol consumption is associated with
      similar risk reductions in CHD among diabetic and nondiabetic men.

PMID- 10920061
TI  - Noninvasive in vivo human coronary artery lumen and wall imaging using black
      blood magnetic resonance imaging.
AB  - BACKGROUND: High-resolution MRI has the potential to noninvasively image the
      human coronary artery wall and define the degree and nature of coronary artery
      disease. Coronary artery imaging by MR has been limited by artifacts related to
      blood flow and motion and by low spatial resolution. METHODS AND RESULTS: We used
      a noninvasive black-blood (BB) MRI (BB-MR) method, free of motion and blood-flow
      artifacts, for high-resolution (down to 0.46 mm in-plane resolution and 3-mm
      slice thickness) imaging of the coronary artery lumen and wall. In vivo BB-MR of
      both normal and atherosclerotic human coronary arteries was performed in 13
      subjects: 8 normal subjects and 5 patients with coronary artery disease. The
      average coronary wall thickness for each cross-sectional image was 0.75+/-0.17 mm
      (range, 0.55 to 1.0 mm) in the normal subjects. MR images of coronary arteries in
      patients with >/=40% stenosis as assessed by x-ray angiography showed localized
      wall thickness of 4.38+/-0.71 mm (range, 3.30 to 5.73 mm). The difference in
      maximum wall thickness between the normal subjects and patients was statistically
      significant (P<0.0001). CONCLUSIONS: In vivo high-spatial-resolution BB-MR
      provides a unique new method to noninvasively image and assess the morphological
      features of human coronary arteries. This may allow the identification of
      atherosclerotic disease before it is symptomatic. Further studies are necessary
      to identify the different plaque components and to assess lesions in asymptomatic
      patients and their outcomes.

PMID- 10920062
TI  - True 3-dimensional reconstruction of coronary arteries in patients by fusion of
      angiography and IVUS (ANGUS) and its quantitative validation.
AB  - BACKGROUND: True 3D reconstruction of coronary arteries in patients based on
      intravascular ultrasound (IVUS) may be achieved by fusing angiographic and IVUS
      information (ANGUS). The clinical applicability of ANGUS was tested, and its
      accuracy was evaluated quantitatively. METHODS AND REUSLTS: In 16 patients who
      were investigated 6 months after stent implantation, a sheath-based catheter was
      used to acquire IVUS images during an R-wave-triggered, motorized stepped
      pullback. First, a single set of end-diastolic biplane angiographic images
      documented the 3D location of the catheter at the beginning of pullback. From
      this set, the 3D pullback trajectory was predicted. Second, contours of the lumen
      or stent obtained from IVUS were fused with the 3D trajectory. Third, the angular
      rotation of the reconstruction was optimized by quantitative matching of the
      silhouettes of the 3D reconstruction with the actual biplane images.
      Reconstructions were obtained in 12 patients. The number of pullback steps, which
      determines the pullback length, closely agreed with the reconstructed path length
      (r=0.99). Geometric measurements in silhouette images of the 3D reconstructions
      showed high correlation (0.84 to 0.97) with corresponding measurements in the
      actual biplane angiographic images. CONCLUSIONS: With ANGUS, 3D reconstructions
      of coronary arteries can be successfully and accurately obtained in the majority
      of patients.

PMID- 10920063
TI  - Application of the New York State PTCA mortality model in patients undergoing
      stent implantation.
AB  - BACKGROUND: This study applied the New York State conventional coronary
      angioplasty (PTCA) model of clinical outcomes to evaluate whether it has
      relevance in the current era of stent implantation. The model was developed in 62
      670 patients treated with conventional PTCA from 1991 to 1994 to risk adjust
      mortality and bypass surgery after PTCA. Since then, stents have become the
      dominant form of intervention. Whether that model remains relevant is uncertain.
      METHODS AND RESULTS: All patients undergoing stenting at the Mayo Clinic from
      1995 to 1998 were analyzed for in-hospital mortality, bypass surgery performed
      after attempted stenting, and longer-term mortality. No patients were excluded.
      The New York model was used to risk adjust and predict in-hospital and follow-up
      mortality. There were 3761 patients with 4063 procedural admissions for stenting;
      6,472 target vessel segments were attempted, and 96.1% of procedures were
      successful. With the New York multivariable risk factor equation, 79 in-hospital
      deaths were expected (1.95%); 66 deaths (1.62%) were observed. The New York model
      risk score in a logistic regression model was the most significant factor
      associated with in-hospital mortality (OR, 1.86; P<0.001). During a mean follow
      up of 1.2+/-1.0 years, there were 154 deaths. Multivariable analysis documented 6
      factors associated with subsequent mortality; New York risk score was the most
      significant (chi(2)=16.64, P=0.0001). CONCLUSIONS: Although the New York
      mortality model was developed in an era of conventional angioplasty, it remains
      relevant in patients undergoing stenting. The risk score derived from that model
      is the variable most significantly associated with not only in-hospital but also
      longer-term outcome.

PMID- 10920065
TI  - Noninvasive imaging of inflammation by ultrasound detection of phagocytosed
      microbubbles.
AB  - BACKGROUND: We have previously shown that microbubbles adhere to leukocytes in
      regions of inflammation. We hypothesized that these microbubbles are phagocytosed
      by neutrophils and monocytes and remain acoustically active, permitting their
      detection in inflamed tissue. METHODS AND RESULTS: In vitro studies were
      performed in which activated leukocytes were incubated with albumin or lipid
      microbubbles and observed under microscopy. Microbubbles attached to the surface
      of activated neutrophils and monocytes, were phagocytosed, and remained intact
      for up to 30 minutes. The rate of destruction of the phagocytosed microbubbles on
      exposure to ultrasound was less (P</=0.05) than that of free microbubbles at all
      acoustic pressures applied. Intravital microscopy and simultaneous ultrasound
      imaging of the cremaster muscle was performed in 6 mice to determine whether
      phagocytosed microbubbles could be detected in vivo. Fifteen minutes after
      intravenous injection of fluorescein-labeled microbubbles, when the blood-pool
      concentration was negligible, the number of phagocytosed/attached microbubbles
      within venules was 7-fold greater in tumor necrosis factor-alpha (TNF-alpha)
      treated animals than in control animals (P<0.01). This increase in retained
      microbubbles resulted in a 5- to 6-fold-greater (P<0.01) degree of ultrasound
      contrast enhancement than in controls. CONCLUSIONS: After attaching to activated
      neutrophils and monocytes, microbubbles are phagocytosed intact. Despite
      viscoelastic damping, phagocytosed microbubbles remain responsive to ultrasound
      and can be detected by ultrasound in vivo after clearance of freely circulating
      microbubbles from the blood pool. Thus, contrast ultrasound has potential for
      imaging sites of inflammation.

PMID- 10920064
TI  - Final results of the Can Routine Ultrasound Influence Stent Expansion (CRUISE)
      study.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) can assess stent geometry more
      accurately than angiography. Several studies have demonstrated that the degree of
      stent expansion as measured by IVUS directly correlated to clinical outcome.
      However, it is unclear if routine ultrasound guidance of stent implantation
      improves clinical outcome as compared with angiographic guidance alone. METHODS
      AND RESULTS: The CRUISE (Can Routine Ultrasound Influence Stent Expansion) study,
      a multicenter study IVUS substudy of the Stent Anti-thrombotic Regimen Study, was
      designed to assess the impact of IVUS on stent deployment in the high-pressure
      era. Nine centers were prospectively assigned to stent deployment with the use of
      ultrasound guidance and 7 centers to angiographic guidance alone with documentary
      (blinded) IVUS at the conclusion of the procedure. A total of 525 patients were
      enrolled with completed quantitative coronary angiography, quantitative coronary
      ultrasound, and clinical events adjudicated at 9 months for 499 patients. The
      IVUS-guided group had a larger minimal lumen diameter (2.9+/-0.4 versus 2.7+/-0.
      5 mm, P<0.001) by quantitative coronary angiography and a larger minimal stent
      area (7.78+/-1.72 versus 7.06+/-2.13 mm(2), P<0.001) by quantitative coronary
      ultrasound. Target vessel revascularization, defined as clinically driven repeat
      interventional or surgical therapy of the index vessel at 9 month-follow-up,
      occurred significantly less frequently in the IVUS-guided group (8.5% versus
      15.3%, P<0.05; relative reduction of 44%). CONCLUSIONS: These data suggest that
      ultrasound guidance of stent implantation may result in more effective stent
      expansion compared with angiographic guidance alone.

PMID- 10920066
TI  - Effects of vitamin E supplementation on F(2)-isoprostane and thromboxane
      biosynthesis in healthy cigarette smokers.
AB  - BACKGROUND: Increased formation of 8-iso-prostaglandin (PG) F(2alpha) and
      thromboxane (TX) A(2), potent agonists of platelet and vascular thromboxane
      (TH)/PGH(2) receptors, has been detected in cigarette smokers. We performed a
      randomized, double-blind, placebo-controlled study of the effects of vitamin E
      (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso-PGF(2alpha)
      and TXA(2) biosynthesis in 46 moderate cigarette smokers. METHODS AND RESULTS:
      Urinary immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2), plasma vitamin E,
      and serum TXB(2) were measured by previously validated techniques. Baseline
      urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion averaged 241+/-78 and
      430+/-293 pg/mg creatinine, respectively. Urinary 8-iso-PGF(2alpha) was
      significantly correlated with 11-dehydro-TXB(2) (r=0.360, n=138, P<0.0001).
      Baseline plasma vitamin E levels averaged 20.6+/-4.9 micromol/L and were
      inversely correlated with urinary 11-dehydro-TXB(2) (r=-0.304, P=0.039) but not
      with 8-iso-PGF(2alpha) (r=-0.227, P=0.129). Vitamin E supplementation caused a
      dose-dependent increase in its plasma levels that reached a plateau at 600 mg
      (42.3+/-11.2 micromol/L, P<0. 001). This was not associated with any
      statistically significant change in urinary 8-iso-PGF(2alpha) or 11-dehydro
      TXB(2) excretion. CONCLUSIONS: Supplementation with pharmacological doses of
      vitamin E has no detectable effects on lipid peroxidation and thromboxane
      biosynthesis in vivo in healthy subjects with a mild degree of oxidant stress.
      These findings are consistent with the hypothesis that the basal rate of lipid
      peroxidation is a major determinant of the response to vitamin E supplementation
      and have implications for the use of vitamin E in healthy subjects as well as for
      the design and interpretation of clinical trials of antioxidant intervention.

PMID- 10920068
TI  - Noradrenergic vascular hyper-responsiveness in human hypertension is dependent on
      oxygen free radical impairment of nitric oxide activity.
AB  - BACKGROUND: Noradrenergic vascular hyper-responsiveness is a hallmark of
      essential hypertension. To evaluate whether nitric oxide plays a role in the
      enhanced vascular response to norepinephrine in hypertension, we examined 32
      hypertensives and 28 normotensives who were distributed in 3 experimental series.
      METHODS AND RESULTS: In the first series, we measured the forearm blood flow
      (FBF) response to a norepinephrine infusion under control conditions and during
      the infusion of L-N-monomethylarginine (L-NMMA). Norepinephrine evoked dose
      dependent vasoconstriction that was greater in hypertensives than in
      normotensives (maximum FBF, -61+/-1 versus -51+/-1%; P<0.01). During L-NMMA
      infusion, norepinephrine vasoconstriction was not modified in hypertensives;
      however, it was potentiated in normotensives (maximum FBF, -64+/-2%; P<0.01). In
      the second series, we tested whether norepinephrine vasoconstriction could be
      affected by an antioxidant such as ascorbic acid. Norepinephrine vasoconstriction
      was blunted by ascorbic acid administration only in hypertensives (maximum FBF, 
      49+/-3 versus -63+/-2%; P<0.01); the vasoconstriction became similar to that
      observed in normotensives. During ascorbic acid plus L-NMMA administration, the
      vascular response to norepinephrine increased to a similar extent in both study
      groups. To rule out the possibility that the effect of ascorbic acid on
      norepinephrine vasoconstriction could depend on adrenergic receptor-induced
      nitric oxide release, in the last series we inhibited endogenous nitric oxide and
      replaced it with an exogenous nitric oxide donor (sodium nitroprusside). Even in
      these conditions, ascorbic acid attenuated norepinephrine vasoconstriction only
      in hypertensives (maximum FBF, -50+/-2 versus -62+/-1%; P<0.01). CONCLUSIONS: Our
      data demonstrate that noradrenergic vascular hyper-responsiveness in hypertension
      is dependent on an impairment of nitric oxide activity that is realized through
      norepinephrine-induced oxygen free radical production.

PMID- 10920067
TI  - Differential effects of beta-blockers in patients with heart failure: A
      prospective, randomized, double-blind comparison of the long-term effects of
      metoprolol versus carvedilol.
AB  - BACKGROUND: Both metoprolol and carvedilol produce hemodynamic and clinical
      benefits in patients with chronic heart failure; carvedilol exerts greater
      antiadrenergic effects than metoprolol, but it is unknown whether this
      pharmacological difference results in hemodynamic and clinical differences
      between the 2 drugs. METHODS AND RESULTS: We randomized 150 patients with heart
      failure (left ventricular ejection fraction </=0.35) to double-blind treatment
      with either metoprolol or carvedilol. When compared with metoprolol (124+/-55
      mg/d), patients treated with carvedilol (49+/-18 mg/d) showed larger increases in
      left ventricular ejection fraction at rest (+10.9+/-11.0 versus +7.2+/-7.7 U,
      P=0.038) and in left ventricular stroke volume and stroke work during exercise
      (both P<0. 05) after 13 to 15 months of treatment. In addition, carvedilol
      produced greater decreases in mean pulmonary artery pressure and pulmonary wedge
      pressure, both at rest and during exercise, than metoprolol (all P<0.05). In
      contrast, the metoprolol group showed greater increases in maximal exercise
      capacity than the carvedilol group (P=0.035), but the 2 drugs improved symptoms,
      submaximal exercise tolerance, and quality of life to a similar degree. After a
      mean of 23+/-11 months of follow-up, 21 patients in the metoprolol group and 17
      patients in the carvedilol group died or underwent urgent transplantation.
      CONCLUSIONS: The present study demonstrates that during long-term therapy,
      carvedilol improves cardiac performance to a greater extent than metoprolol when
      administered to patients with heart failure in the doses shown to be effective in
      clinical trials. These differences were likely related to a greater
      antiadrenergic activity of carvedilol.

PMID- 10920069
TI  - Assessment of severity of aortic regurgitation using the width of the vena
      contracta: A clinical color Doppler imaging study.
AB  - BACKGROUND: The width of the vena contracta (VC-W), the smallest area of
      regurgitant flow, reflects the degree of valvular regurgitation and is measurable
      by color Doppler imaging, but this method has not been validated in aortic
      regurgitation (AR). METHODS AND RESULTS: We prospectively examined 79 patients
      with isolated AR and 80 patients without regurgitation. The VC-W was measured
      from the long-axis parasternal view and compared with 2 simultaneous reference
      methods (quantitative Doppler and 2D echocardiography). In patients without
      regurgitation, the agreement between methods was excellent. In patients with AR,
      good correlations (all P<0.0001) were obtained between VC-W and effective
      regurgitant orifice (ERO) area and regurgitant volume recorded by quantitative
      Doppler (r=0.89 and 0.90, respectively) and 2D echocardiographic (r=0.90 and
      0.89, respectively) methods. These correlations were similar with eccentric or
      central jets (all P>0.60). The other methods used showed good correlations of VC
      W with aortographic grading of AR (n=8, r=0.82, P=0.01), with the proximal flow
      convergence method (n=53, r=0.85, P<0.0001), and with left ventricular end
      diastolic volume (r=0.81, P<0.0001). Sensitivity and specificity of VC-W >/=6 mm
      for diagnosing severe AR (ERO >/=30 mm(2)) were 95% and 90%, respectively.
      CONCLUSIONS: For assessment of the degree of AR, VC-W shows good correlations
      with simultaneous quantitative measures (regardless of jet direction), shows good
      correlations with other methods of assessment of AR, and provides a high
      diagnostic value for severe AR. VC-W is a simple, reliable method that can be
      used clinically as part of comprehensive Doppler echocardiographic assessment of
      AR.

PMID- 10920070
TI  - Adenovirus-mediated VEGF(121) gene transfer stimulates angiogenesis in
      normoperfused skeletal muscle and preserves tissue perfusion after induction of
      ischemia.
AB  - BACKGROUND: Administration of angiogenic factors stimulates neovascularization in
      ischemic tissues. However, there is no evidence that angiogenesis can be induced
      in normoperfused skeletal muscles. We tested the hypothesis that adenovirus
      mediated intramuscular (IM) gene transfer of the 121-amino-acid form of vascular
      endothelial growth factor (AdCMV.VEGF(121)) could stimulate neovascularization in
      nonischemic skeletal muscle and consequently attenuate the hemodynamic deficit
      secondary to surgically induced ischemia. METHODS AND RESULTS: Rabbits and rats
      received IM injections of AdCMV.VEGF(121), AdCMV.Null, or saline in the thigh, 4
      weeks (rabbits) or 2 weeks (rats) before femoral artery removal in the injected
      limb. In unoperated rats, at the site of injection of AdCMV.VEGF(121), we found
      96% and 29% increases in length density of arterioles and capillaries,
      respectively. Increased tissue perfusion (TP) to the ischemic limb in the
      AdCMV.VEGF(121) group was documented, as early as day 1 after surgery, by
      improved blood flow to the ischemic gastrocnemius muscle measured by radioactive
      microspheres (AdCMV.VEGF(121)=5.69+/-0.40, AdCMV.Null=2.97+/-0.50, and
      saline=2.78+/-0.43 mL x min(-1) x 100 g(-1), P<0.001), more angiographically
      recognizable collateral vessels (angioscore) (AdCMV. VEGF(121)=50.58+/-1.48,
      AdCMV.Null=29.08+/-4.22, saline=11.83+/-1.90, P<0.0001), and improvement of the
      bioenergetic reserve of the gastrocnemius muscle as assessed by (31)P NMR
      spectroscopy. Follow-up studies showed that superior TP to the ischemic limb in
      the AdCMV.VEGF(121) group persisted until it was equalized by spontaneous
      collateral vessel development in untreated animals. CONCLUSIONS: IM
      administration of AdCMV.VEGF(121) stimulates angiogenesis in normoperfused
      skeletal muscles, and the newly formed vessels preserve TP after induction of
      ischemia.

PMID- 10920071
TI  - Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: In vivo
      study.
AB  - BACKGROUND: The precise molecular mechanism of Adriamycin-induced cardiomyopathy
      (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial
      cell death and the apoptosis-inducing molecules in ADR-CM induced in rats.
      METHODS AND RESULTS: Until 8 weeks after the first administration of ADR, there
      was no increase in the number of labeled cells by terminal deoxynucleotidyl
      transferase assay (TUNEL method). Apoptotic indices increased significantly at
      weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control
      group (0.42+/-0.12% versus 0.10+/-0.02% and 0.86+/-0.11% versus 0.09+/-0.04% at
      weeks 9 and 10, respectively). DNA ladder formation was also observed in the
      myocardial tissues during the late stages of the ADR-CM of rats. There was no
      significant difference in expression of p53 gene between the ADR group and the
      control group at either the message or the protein level. An overexpression of
      Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10
      by both Western blotting and immunofluorescent staining. Furthermore, we
      confirmed that neutralization of anti-Fas ligand antibody inhibited ADR-induced
      apoptosis. CONCLUSIONS: Apoptotic cell death was observed in the hearts of ADR-CM
      rats, and the number of apoptotic myocardial cells increased with the
      deterioration of morphological findings and cardiac function, indicating that
      apoptosis may be an important mechanism of loss of myocardial cells and cardiac
      dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather
      is executed through a Fas-mediated pathway.

PMID- 10920072
TI  - Favorable remodeling enhances recovery of regional myocardial function in the
      weeks after infarction in ischemically preconditioned hearts.
AB  - BACKGROUND: In a previous study, we found that recovery of segment shortening in
      the ischemic zone of conscious, chronically instrumented rabbits was
      significantly better in ischemically preconditioned than control animals after 72
      hours of reperfusion. However, although this period of reperfusion was felt to be
      sufficient to allow recovery from stunning, regional function was
      disproportionately low for the size of the infarcts. METHODS AND RESULTS: To
      further characterize the recovery of left ventricular regional function, rabbits
      were chronically instrumented with a balloon occluder around a branch of the left
      coronary artery and a pair of ultrasonic crystals to monitor segment shortening
      in the ischemic zone. The preconditioned group had 1 cycle of 5-minute
      occlusion/10-minute reperfusion before a 30-minute occlusion, whereas control
      rabbits experienced only the 30-minute occlusion. All monitored segments were
      either dyskinetic or akinetic during the 30-minute occlusion. There was no
      difference in function between the 2 groups until 24 hours of reperfusion. At 72
      hours, systolic shortening in control hearts averaged only 5% of the preischemic
      value, whereas shortening was 29% of baseline in preconditioned hearts. By day
      21, systolic shortening averaged 26% in control hearts and 65% in preconditioned
      hearts (P<0.02) and appeared to have reached a plateau. Infarct size was 31.4+/
      2.8% and 15.5+/-2.1% in control and preconditioned hearts, respectively.
      Moreover, in ischemically preconditioned hearts, the recovery of regional
      function was better than in controls for any given amount of microinfarction in
      the myocardial segment between crystals (P=0.02). CONCLUSIONS: The progressive
      improvement in preconditioned hearts is most consistent with favorable remodeling
      in the ischemic zone, which the preconditioning process seems to accentuate.

PMID- 10920074
TI  - Photoangioplasty: An emerging clinical cardiovascular role for photodynamic
      therapy.
AB  - Photodynamic therapy (PDT) has been studied and applied to various disease
      processes. The potential of PDT for selective destruction of target tissues is
      especially appealing in cardiovascular disease, in which other existing
      interventional tools are somewhat nonselective and carry substantial risk of
      damage to the normal arterial wall. Enthusiasm for photoangioplasty (PDT of
      vascular de novo atherosclerotic and, potentially, restenotic lesions) is fueled
      by more effective second-generation photosensitizers and technological advances
      in endovascular light delivery. This excitement revolves around at least 4
      significant attributes of light-activated therapy: the putative selectivity and
      safety of photoangioplasty, the potential for atraumatic and effective debulking
      of atheromatous plaque through a biological mechanism, the postulated capability
      to reduce or inhibit restenosis, and the potential to treat long segments of
      abnormal vessel by simply using fibers with longer light-emitting regions. The
      available nonclinical data, coupled with the observations of a new phase I trial
      in human peripheral atherosclerosis, suggest a promising future for
      photoangioplasty in the treatment of primary atherosclerosis and prevention of
      restenosis.

PMID- 10920073
TI  - Arrhythmogenic mechanism of an LQT-3 mutation of the human heart Na(+) channel
      alpha-subunit: A computational analysis.
AB  - BACKGROUND: D1790G, a mutation of SCN5A, the gene that encodes the human Na(+)
      channel alpha-subunit, is linked to 1 form of the congenital long-QT syndrome
      (LQT-3). In contrast to other LQT-3-linked SCN5A mutations, D1790G does not
      promote sustained Na(+) channel activity but instead alters the kinetics and
      voltage-dependence of the inactivated state. METHODS AND RESULTS: We modeled the
      cardiac ventricular action potential (AP) using parameters and techniques
      described by Luo and Rudy as our control. On this background, we modified only
      the properties of the voltage-gated Na(+) channel according to our patch-clamp
      analysis of D1790G channels. Our results indicate that D1790G-induced changes in
      Na(+) channel activity prolong APs in a steeply heart rate-dependent manner not
      directly due to changes in Na(+) entry through mutant channels but instead to
      alterations in the balance of net plateau currents by modulation of calcium
      sensitive exchange and ion channel currents. CONCLUSIONS: We conclude that the
      D1790G mutation of the Na(+) channel alpha-subunit can prolong the cardiac
      ventricular AP despite the absence of mutation-induced sustained Na(+) channel
      current. This prolongation is calcium-dependent, is enhanced at slow heart rates,
      and at sufficiently slow heart rate triggers arrhythmogenic early
      afterdepolarizations.

PMID- 10920076
TI  - : august 1, 2000

PMID- 10920075
TI  - Images in cardiovascular medicine. Aortic dissection at the coronary artery
      sinus: magnetic resonance angiography findings.

PMID- 10920077
TI  - Three-dimensional phlebography of the saphenous venous system.

PMID- 10920078
TI  - Appointment of new editor-in-chief

PMID- 10920079
TI  - Geographical distribution of publications in Human Reproduction and Fertility and
      Sterility in the 1990s.
AB  - Curious about the geographical distribution of publications in reproductive
      medicine, we compared the numbers of publications in Human Reproduction (HR) and
      Fertility and Sterility (F&S). The annual number of publications from the
      individual countries was obtained by searching the Medline database using the
      internet provider PubMed. The data were analysed and normalized to population
      size, gross domestic product (GDP) and total number of Medline publications. The
      8511 publications of both journals in the 1990s came from 56 countries. The
      number of publications per year was increasing in HR and remained constant in
      F&S. In absolute numbers, the UK produced the most publications in HR (21%) and
      the USA in F&S (45%) as well as in both journals together (28%). Relatively,
      Israel was the most productive country per million inhabitants (8.4 +/- 2.1
      publications/year), per billion US dollars GDP (0.85 +/- 0.21 publications/year)
      and per 1000 Medline publications (15 +/- 4 publications/year). Europe was the
      most productive world region in absolute numbers (54%) and Australia/New Zealand
      in relative numbers per million inhabitants and per 1000 billion US dollars GDP.
      Almost 87% of all publications in HR and F&S came from the 18 countries with a
      GDP per capita of >10 000 US dollars. In conclusion, the geographical
      distribution of publications in HR and F&S follows the pattern of the
      distribution of publications in general biomedical research. Most publications
      come from affluent countries. Although the USA and the UK appear to be the most
      productive countries in absolute numbers, smaller affluent countries like Israel
      and Belgium are more productive when the numbers are normalized to population or
      GDP.

PMID- 10920080
TI  - The case for routine HIV screening before IVF treatment: a survey of UK IVF
      centre policies.
AB  - The case for routine human immunodeficiency virus (HIV) screening of all couples
      seeking assisted reproductive treatment is so strong that it should be made
      obligatory for all couples entering IVF programmes to be given information about
      HIV transmission, and offered testing. In August 1999, questionnaires regarding
      routine HIV screening of couples seeking IVF treatment were sent to the medical
      directors of the 74 licensed assisted conception units in the UK. Of the 45
      (60.8%) centres who responded, 19 (42.2%) routinely screen both partners for HIV
      antibodies, 25 (55.5%) do not screen and one centre selectively screens high-risk
      patients. There was no significant difference in the proportion of centres that
      routinely carried out screening with regards to the unit size: six out of 13
      (46.2%) small units compared with 13/32 (40.6%) large units. In all, 17 centres
      (37.8%) rated HIV screening as essential, nine (20%) as desirable, 11 (24.4%) as
      not required, while eight (17. 8%) centres did not comment. Of the 19 centres
      that have a routine screening policy, 18 have management protocols in the event
      that the test is positive. Of these 18 centres, 12 adhere rigidly to the
      protocol, while five centres adhere to the protocol with few exceptions and the
      remaining one uses its protocol for guidance only. The main reasons for not
      employing routine HIV screening were: the lack of cost effectiveness, low
      prevalence of HIV infection in their population, necessity for and cost of
      counselling, uncertainty about the need for screening and potential delay to
      start of treatment.

PMID- 10920081
TI  - Avoiding multiple pregnancies in ART: replace as many embryos as you like-one at
      a time.

PMID- 10920082
TI  - Avoiding multiple pregnancies in ART. Double trouble: yes a twin pregnancy is an
      adverse outcome.

PMID- 10920083
TI  - Fourier transform infrared spectroscopy of follicular fluids from large and small
      antral follicles.
AB  - Fourier transform infrared spectroscopy (FTIR) was used to obtain 'biochemical
      fingerprints' for the constitution of follicular fluids from large and small
      antral luteinized follicles (n = 54 pairs). All samples gave reproducible
      characteristic biological infrared absorption spectra, with recognizable amide I
      protein vibrations and acyl vibrations from fatty acids. Discriminant function
      analysis of the first derivative FTIR spectra, together with hierarchical cluster
      analysis used to construct a dendrogram, showed fluid from large follicles formed
      a homogeneous closely related cluster, whilst that from small follicles was
      distinct from the large, and heterogeneous in nature. The large follicle fluids
      showed closer biochemical similarity to each other than to the corresponding
      fluid taken from small matched follicles. An artificial neural network was
      trained and following validation with an independent test set, successfully
      distinguished follicular fluids from large and small follicles. The sex steroid
      concentrations in the fluids from large and small follicles were significantly
      different. These results show that fluid from large follicles is distinct in
      biochemical nature from that from small follicles, but the degree of homogeneity
      implies size-specific changes take place. These may have consequences for the
      developmental potential of the oocyte.

PMID- 10920084
TI  - Adipocyte insulin action in hypogonadotrophic hypogonadism.
AB  - In-vitro studies of adipose tissue have shown that patients with polycystic
      ovarian syndrome (PCOS) have marked insulin resistance, the abnormalities being
      more pronounced during amenorrhoea compared to following an ovulatory cycle. If
      the insulin resistance in PCOS is a reflection of anovulation then patients with
      hypogonadotrophic hypogonadism (HH) should also have a reduction in insulin
      sensitivity. This study was designed to investigate insulin sensitivity in
      patients with HH. Seven patients with HH were studied and compared with eight age
      and body mass index matched female controls. Adipocyte insulin receptor binding
      was measured and adipocyte insulin action was assessed by measuring initial rates
      of 3-O-methylglucose uptake and inhibition of lipolysis. The specific insulin
      receptor binding per 10 cm(2) cell surface was 0.95 +/- 0. 25% in HH and 1.85 +/-
      0.14% in control patients (P < 0.01). Maximum rates of glucose uptake were also
      impaired in HH compared with controls (3-O-methylglucose transport 0.81 +/- 0.22
      versus 1.83 +/- 0.2 pmol/10 cm(2)/5 s)(P < 0.01). Hence, patients with HH have
      impaired insulin sensitivity to a degree similar to that seen in PCOS, suggesting
      a direct effect of anovulation on insulin sensitivity.

PMID- 10920085
TI  - No evidence of increased uterine vascular impedance with patient ageing following
      IVF.
AB  - A study was conducted to determine if uterine vascular impedance increases with
      advancing age in women undergoing ovarian stimulation for IVF. A group of 162
      women who had undergone conventional IVF and embryo transfer was subdivided into
      three subgroups by age: 30-34 years (n = 49), 35-39 years (n = 79) and 40-44
      years (n = 34). The pulsatility index (PI) and resistance index (RI) of the right
      and left uterine arteries were measured at baseline, on the day of oocyte
      retrieval, and at the mid-luteal phase. There were no differences in the average
      PI or RI by age at any phase of the cycle. In all age groups, the luteal phase
      values of PI and RI were lower than those observed earlier in the cycle.
      Endometrial thickness was not associated with age. There was no significant
      correlation between PI, RI and serum oestradiol and progesterone concentrations
      at any phase of the cycle. Ovarian response, as measured by average number of
      oocytes retrieved, decreased significantly with age. Thus, reduced pregnancy
      rates in older women undergoing ovarian stimulation are more likely to occur
      because of oocyte quality and quantity rather than uterine senescence. If future
      studies determine that the use of ovarian stimulation does decrease implantation
      rates more in older versus younger women, a mechanism other than increased
      uterine vascular impedance must be sought.

PMID- 10920086
TI  - Impact of oestradiol and inhibin A concentrations on pregnancy rate in in-vitro
      oocyte maturation.
AB  - The purpose of the present study was to analyse the results of maturation of
      oocytes obtained in unstimulated normal women after a leading follicle of 10 mm
      diameter and an endometrium of at least 5 mm thickness were observed at
      ultrasound. The serum concentrations of oestradiol and inhibin A were analysed
      from day 3 to the day of aspiration and retrospectively evaluated. A total of 75
      normal regular cycling women referred for IVF/intracytoplasmic sperm injection
      (ICSI) because of male factor and/or tubal disease was included (n = 87
      consecutive cycles). The oocytes were aspirated transvaginally and matured for 28
      36 h. ICSI was performed on all metaphase II oocytes and they were cultured to
      day 2 or 3 after insemination, at which time suitable embryos (maximum two) were
      replaced into the women. Eleven singleton pregnancies with a live fetus were
      obtained after transfer in 63 cycles (pregnancy rate of 13% per aspiration and
      17% per transfer). Nine healthy children have been born and the remaining two
      pregnancies miscarried in the eighth to ninth gestational week. The serum
      concentrations of oestradiol on day 3 and on the day of aspiration were available
      in 85 cycles, and in 57 of these an increase of 100% was detected on the day of
      aspiration. Significantly more pregnancies were observed in these cycles compared
      with cycles without an increase in the concentration of oestradiol (19 versus 0%
      per aspiration, 24 versus 0% per transfer, P < 0.02). Further improvement in
      pregnancy rate was obtained if aspiration was performed after increase in inhibin
      A concentration (24 versus 0% per aspiration and 33 versus 0% per transfer, P <
      0.02) (n = 83 cycles, where inhibin concentrations were available, and n = 42
      cycles, where an increase of 80% was detected on the day of aspiration compared
      with day 3). Timing of aspiration may improve the developmental potential of
      immature oocytes.

PMID- 10920087
TI  - Ovarian stimulation during assisted reproduction treatment: a comparison of
      recombinant and highly purified urinary human FSH. On behalf of The Feronia and
      Apis study group.
AB  - This randomized, single-blind, multicentre, multinational study compared
      recombinant human FSH (rhFSH, Gonal-F) with highly purified urinary human FSH
      (uhFSH, Metrodin HP) in women undergoing ovarian stimulation for
      IVF/intracytoplasmic sperm injection (ICSI). Following desensitization in a long
      gonadotrophin-releasing hormone (GnRH) agonist protocol, patients received s.c.
      Gonal-F or Metrodin HP, at a fixed dose of 150 IU, until there was adequate
      follicular development. Of 496 women randomized, 232 and 231 in the Gonal-F and
      Metrodin HP groups respectively received human chorionic gonadotrophin (HCG). The
      duration of FSH treatment was significantly shorter with Gonal-F than with
      Metrodin HP (11.6 +/- 1.9 days versus 12. 4 +/- 2.7 days; P < 0.0001) and
      significantly fewer ampoules were required (mean 22.6 +/- 5.0 versus 24.3 +/-
      5.1, P < 0.0002). There were, however, significantly more follicles > or =10 mm
      in diameter with Gonal-F (15.6 +/- 8.2 versus 13.6 +/- 7.1, P < 0.01) and oocytes
      retrieved (13.1 +/- 7.7 versus 11.4 +/- 7.6, P < 0.002). Although no statistical
      difference in pregnancy rate was recorded, patients receiving Gonal-F had a
      higher pregnancy rate per cycle than patients given Metrodin HP (25.1 versus
      20.1%). Moderate to severe ovarian hyperstimulation syndrome occurred in 2.8 and
      1.2% of Gonal-F and Metrodin HP patients respectively (not significant). In
      conclusion, FSH stimulation in combination with a long GnRH agonist protocol is
      effective in inducing multiple follicular development and embryos with a high
      implantation potential. However, Gonal-F is clearly more effective than Metrodin
      HP in inducing multifollicular development.

PMID- 10920088
TI  - Three-dimensional endometrial volume estimation as a predictor of pituitary down
      regulation in an IVF-embryo transfer programme.
AB  - To examine the role of three-dimensional (3D) volume estimation in predicting
      pituitary down-regulation in an IVF-embryo transfer programme, 46 women were
      treated with buserelin acetate for down-regulation prior to and concomitantly
      with ovarian stimulation. Receiver operating characteristic (ROC) curve analysis
      was used for statistics. The area under the curve (AUC) provides a measure to
      show how good (AUC close to 1) or how poor (AUC close to 0.5) a test is. If down
      regulation was defined as oestradiol <40, <60 or <80 pg/ml, the AUC of 3D
      ultrasound was 0.57, 0.83 and 0.97 respectively. The highest sensitivity (100%)
      and specificity (93.2%) of 3D-ultrasound was achieved if down-regulation was
      defined as oestradiol <80 pg/ml (n = 44), with an endometrial volume of 1.9 ml.
      If down-regulation was defined as oestradiol <60 pg/ml (n = 42) the best
      combination of highest sensitivity (95.2%) and specificity (75. 0%) was obtained
      with an endometrial volume of 1.9 ml. The comparison of 3D volume calculation
      with endometrial thickness measurement revealed no significant difference in
      predicting down-regulation. 3D volume estimation provides a new tool for
      diagnosing relative hypo-oestrogenism or down-regulation, but it was not superior
      to two-dimensional ultrasound.

PMID- 10920090
TI  - Three pregnancies despite elevated serum FSH and advanced age: case report.
AB  - Although the transfer of fertilized donor oocytes is the most efficacious mode of
      conception for infertile women with hypergonadotrophism associated with incipient
      or apparent ovarian failure, there are many individuals who, for religious,
      ethical, or personal reasons, would prefer to try to conceive with their own
      oocytes. The three cases presented here represent extremes to date for (i)
      highest serum FSH concentration in a woman with incipient ovarian failure (n =
      2), and (ii) the oldest woman with apparent overt ovarian failure (n = 1) to have
      successful pregnancies. All three cases were treated for only a short time with
      pharmacological dosages of ethinyl oestradiol with luteal phase support with
      progesterone. The peak FSH (mIU/ml) in cases 1 and 2 was 143 and 127
      respectively. The precedents set in these cases can help physician-patient
      consultation when patients enquire whether there is a certain critical FSH
      concentration above which pregnancy is not possible or an age over which
      successful pregnancy could not be achieved even if ovulation despite ovarian
      failure was possible.

PMID- 10920089
TI  - Increasing paternal age is associated with delayed conception in a large
      population of fertile couples: evidence for declining fecundity in older men. The
      ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood).
AB  - The impact of male age on fecundity remains controversial. Here, a large
      population study was used to investigate the effect of paternal age on time to
      conception. All couples in the Avon Health district expecting a baby between 1
      April 1991 and 31 December 1992 were eligible. Questionnaires completed by both
      the man and the woman at 18 weeks gestation covered specific fertility factors,
      e.g. parity, paternity, cohabitation and oral contraception; and non-specific
      factors, e.g. educational achievement, housing, cigarette smoking, alcohol
      consumption, obesity. Logistic regression was used to identify factors
      independently related to conception in < or =6 or < or =12 months. Of 8515
      planned pregnancies, 74% were conceived in < or =6 months, 14% in the second 6
      months and 12% after more than a year. Nine variables, including the age of the
      woman, were independently related to time to conception. After adjustment for
      these, the likelihood of conception within 6 or 12 months was lower in older men.
      Compared to men <25 years old, the adjusted odds ratios (95% confidence interval)
      for conception in < or =12 months were 0.62 (0.40, 0.98), 0.50 (0.31, 0.81) and
      0.51 (0.31, 0.86) in men aged 30-34, 35-39 and > or =40 years respectively.

PMID- 10920092
TI  - Sperm chromatin structure assay parameters as predictors of failed pregnancy
      following assisted reproductive techniques.
AB  - The predictive value of sperm chromatin integrity for pregnancy outcome following
      in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) was
      studied in 24 men attending a university-based assisted reproductive techniques
      laboratory using the flow cytometric sperm chromatin structure assay (SCSA). The
      SCSA is a measure of the susceptibility of sperm DNA to low pH-induced
      denaturation in situ. The mean percentage of spermatozoa in the neat sample
      demonstrating DNA denaturation was significantly lower in the seven men that
      initiated a pregnancy (15.4 +/- 4.6, P = 0.01) than in the 14 men who did not
      initiate a pregnancy (31.1 +/- 3.2). No pregnancies resulted if > or =27% of the
      spermatozoa in the neat semen sample showed DNA denaturation. These data
      demonstrate that SCSA parameters are independent of conventional semen
      parameters. Furthermore, the SCSA may allow physicians to identify male patients
      for whom IVF and ICSI will be unlikely to result in pregnancy initiation.

PMID- 10920091
TI  - In-vitro differentiation of germ cells from frozen testicular biopsy specimens.
AB  - In some men with germ cell maturation arrest, spermatogenesis can be resumed
      during in-vitro culture of testicular biopsy samples. In this study, we examined
      whether similar differentiation events can be induced in cultured germ cells from
      cryopreserved testicular biopsy specimens. Fresh and cryopreserved aliquots of
      the same testicular biopsy samples were cultured in medium supplemented with FSH
      and testosterone. After 24 and 48 h of culture, the progression of
      spermatogenesis and the percentage of Sertoli cells with DNA damage, detected by
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL),
      were evaluated. Spermatogenesis progressed in a similar way in fresh and
      cryopreserved aliquots over the first 24 h of culture. However, in contrast to
      fresh aliquots, no additional progress of spermatogenesis was detected between
      the 24 and 48 h time points. The percentage of TUNEL-positive Sertoli cells in
      fresh aliquots showed only a moderate increase after 24 h of culture, whereas
      most Sertoli cells from cryopreserved aliquots became TUNEL-positive during the
      same culture period. These data show that limited progression of spermatogenesis
      can be achieved by culturing cryopreserved testicular biopsy specimens for 24 h,
      but no additional benefit can be expected from prolonging the culture beyond this
      time point.

PMID- 10920093
TI  - Assessment of testicular core temperatures using microwave thermography.
AB  - A new method for the reliable assessment of testicular core temperature using
      microwave technology is presented. This study was designed to assess whether
      alterations in testicular thermoregulation could be reliably demonstrated in
      patients with clinically apparent varicoceles (n = 36), in those with idiopathic
      male infertility (n = 52) and in fertile donors (n = 20) using this new microwave
      thermographic technique. The measurements obtained were found to be reliable and
      reproducible. Testicular core temperature measurements were significantly
      different between the groups (P < 0.001). Furthermore, there was a temperature
      gradient between the scrotal neck and the testicular core in all groups;
      testicular core temperatures were lower than scrotal neck temperatures. The
      magnitude of this temperature difference was also significantly different (P <
      0.001) between the groups. Microwave testicular thermography is a new technique
      that is safe and accurate. Preliminary results suggest altered testicular
      thermoregulation in a group of patients with impaired spermatogenesis with and
      without varicocele. Testicular temperature profiles obtained by microwave
      thermography may be of value in the assessment of infertile men with or without a
      varicocele.

PMID- 10920094
TI  - Sperm motility index: a quick screening parameter from sperm quality analyser-IIB
      to rule out oligo- and asthenozoospermia in male fertility study.
AB  - The aim of this study was to evaluate the sperm quality analyser (SQA)-IIB, a new
      automated sperm analyser, and to compare its results with those obtained with a
      method based on the World Health Organization recommendations. Eighty-nine
      unprocessed semen samples and 53 selected sperm suspensions were analysed.
      Concentration, motility and morphology were evaluated using the routine
      laboratory method. The SQA-IIB measured the sperm motility index (SMI) and
      estimated the previously mentioned parameters. In the imprecision assay a maximal
      coefficient of variation (CV) of 18.8% was found. A semen sample with
      immunological factor showed a CV of 75.75%, which invalidates its use for these
      types of samples. A good correlation was obtained between SMI and concentration
      of progressively motile spermatozoa (CPMS) (r = 0.87), and a fair correlation
      with the other parameters. There was no statistically significant correlation
      between both methods for normal sperm morphology. The sensitivity and specificity
      of the SMI test in relation to CPMS were 96 and 84% respectively, for an SMI
      threshold value of 160. The results obtained make the SQA-IIB a good screening
      test to rule out oligozoospermia and asthenozoospermia when studying the male
      factor in the sterility outpatient clinics. However, the results suggested that
      it is not a valid method to evaluate morphology.

PMID- 10920095
TI  - Serum inhibin B determination is predictive of successful testicular sperm
      extraction in men with non-obstructive azoospermia.
AB  - Recent work indicates that serum inhibin B is a useful marker of spermatogenesis
      and inhibin B production sufficient to maintain detectable serum concentrations
      in adults depends on spermatogenic activity. The purpose of the present study was
      to investigate the usefulness of serum inhibin B measurement to predict the
      success of testicular sperm extraction (TESE) in 17 men with nonobstructive
      azoospermia to be treated by intracytoplasmic sperm injection (ICSI) (group 1).
      Two additional groups were used as positive controls; group 2 comprised 22
      infertile men having obstructive azoospermia, and group 3, which included 29
      semen donors having normal seminal parameters. Follicle stimulating hormone (FSH)
      was significantly higher (P < 0.01) and inhibin B significantly lower (P <
      0.001), in group 1 as compared with groups 2 and 3. Serum inhibin B
      concentrations were significantly higher (P < 0.001) among successful TESE men as
      compared with those having failed TESE. In contrast, no differences were detected
      between these two groups with respect to serum FSH or testicular size. In
      addition, serum inhibin B but not FSH discriminated between successful and failed
      TESE in group 1 subjects as compared with control groups. According to the
      receiver operating characteristics curve analysis, the best inhibin B value for
      discriminating between successful and failed TESE was >40 pg/ml (sensitivity 90%,
      specificity 100%). It is concluded that inhibin B measurement is a useful non
      invasive predictor of spermatogenesis and thus, all azoospermic males should have
      serum inhibin B concentrations determined in addition to FSH measurement and
      karyotyping prior to undergoing TESE.

PMID- 10920096
TI  - Effects of cryopreservation on progesterone-induced ion fluxes and acrosome
      reaction in human spermatozoa.
AB  - The present study evaluated the effects of cryopreservation on progesterone
      induced variations of calcium ion concentration [Ca(2+)](i), plasma membrane
      potential and acrosome reaction in human spermatozoa. Spermatozoa from 10 fertile
      donors were divided in two equivalent aliquots, one used as control (fresh
      spermatozoa) and the other used after freezing-thawing. Measurement of
      spermatozoa [Ca(2+)](i) before and after freezing-thawing showed a significant
      reduction of basal [Ca(2+)](i) in thawed spermatozoa (P < 0.01). Progesterone
      induced a rise of [Ca(2+)](i) both in fresh and thawed spermatozoa with a
      significant reduction after freezing-thawing (P < 0.01). The monitoring of sperm
      plasma membrane potential demonstrated that progesterone induced plasma membrane
      depolarization in fresh spermatozoa that was absent in thawed spermatozoa. The
      inhibitory effects of freezing-thawing on progesterone induced [Ca(2+)](i) and
      plasma membrane potential variations in human spermatozoa were closely related to
      the inhibition of the acrosome reaction. In conclusion the present study
      demonstrates that freezing-thawing procedures reduce the responsiveness of human
      spermatozoa to progesterone in terms of [Ca(2+)](i) rise and completely inhibit
      its effects on plasma membrane potential variations, thus supporting the
      hypothesis that freezing-thawing procedures may differently modify the plasma
      membrane receptors for progesterone in human spermatozoa which are known to
      express at least two receptors for this steroid in their plasma membrane.

PMID- 10920097
TI  - Relationship between endometriotic foci and nerves in rectovaginal endometriotic
      nodules.
AB  - The histological relationships between fibrotic tissue, endometriotic foci and
      nerves in the rectovaginal septum endometriotic or adenomyotic nodule were
      studied. This is considered to be one of the most severe forms of deep
      endometriosis. Masson's trichrome staining for fibrosis detection and
      immunohistochemistry with the S100 monoclonal antibody for nerve detection were
      performed in 28 rectovaginal endometriotic nodules from patients presenting with
      severe dysmenorrhoea and deep dyspareunia (23 patients with no other
      endometriotic location or potential cause of pain at laparoscopy and
      ultrasonography; five patients with multiple pelvic endometriotic localizations
      and other potential causes of pain at laparoscopy). Patients were allocated to
      two groups on the basis of their preoperative pain scores for pelvic pain,
      dysmenorrhoea and deep dyspareunia (group 1, score >7; group 2, score < or =7).
      For each symptom, the mean number of nerves and endometriotic lesions per high
      power field and the mean largest diameter of the lesions were not statistically
      different in groups 1 and 2. The mean percentages of nerves located within the
      fibrosis of the nodule and within endometriotic lesions were significantly higher
      in group 1 than in group 2. Among nerves located within endometriotic lesions,
      there was a significantly higher proportion showing intraneurial and perineurial
      invasion by endometriosis in group 1 than in group 2. In rectovaginal
      endometriotic nodules, there was a close histological relationship between nerves
      and endometriotic foci, and between nerves and the fibrotic component of the
      nodule. We postulate that such topographical relationships could at least
      partially explain the strong association between this lesion and pain.

PMID- 10920098
TI  - Prognostic factors of reproductive outcome after myomectomy in infertile
      patients.
AB  - The objective of this study was to identify the prognostic factors for conception
      after myomectomy carried out in cases of infertility. A total of 91 infertile
      patients presenting at least one subserous or intramural myoma measuring >2 cm
      underwent myomectomy. The characteristics of the patients, myomata and associated
      infertility factors were collected in a uniform and systematic way. A postal
      questionnaire was sent to patients. For each of the various factors studied, the
      specific cumulative probability of spontaneous intrauterine conception was
      estimated using the Kaplan-Meier method. Multiple regression analysis was then
      carried out using Cox's proportional hazards model. The cumulative probability of
      spontaneous intrauterine conception at 2 years follow-up was 44% (95% confidence
      interval: 32-56%). The cumulative probability of conception was less after
      removal of a posterior or intramural myoma, after a sutured hysterotomy, and when
      accompanied by a male factor, associated tubal or ovulation pathology. The
      cumulative probability of conception was greater after ablation of myomata
      responsible for menometrorrhagia. The size, deforming effect on the cavity and
      age played no role in our sample. Our results indirectly suggest that post
      myomectomy adhesions could have an adverse effect on fertility. Myomata
      responsible for menometrorrhagia are also the cause of infertility. In the
      presence of an associated male, tubal or ovulatory factor, the results were poor
      and it was not possible to determine if a myomectomy should be performed in these
      cases in order to enhance fertility.

PMID- 10920099
TI  - Hypoxaemia induced by CO(2) or helium pneumoperitoneum is a co-factor in adhesion
      formation in rabbits.
AB  - A prospective randomized trial in a rabbit model was performed to test the
      hypothesis that the increase in adhesion formation following prolonged
      pneumoperitoneum is mediated by peritoneal hypoxaemia. Laparoscopic standardized
      opposing lesions were performed in uterine horns and pelvic sidewalls by bipolar
      coagulation and CO(2) laser in six groups of eight animals. Pure CO(2) or helium
      pneumoperitoneum was used for 10 (groups I and IV) or 45 min (groups II and V) to
      confirm the effect of duration of pneumoperitoneum and 96% of CO(2) or helium
      with 4% of oxygen (group III and VI) for 45 min to assess the effect of the
      addition of oxygen. After 7 days, adhesion formation was scored by laparoscopy.
      By two-way analysis of variance, total, extent, type and tenacity of adhesion
      scores increased (P = 0.0003, P = 0.0004, P = 0.0004 and P = 0.004) with
      increasing duration of pneumoperitoneum and decreased (P = 0.02, P = 0.03, P =
      0.01 and P = 0.05) with the addition of oxygen. No differences were found between
      CO(2) and helium. In conclusion these data confirm the effect of pneumoperitoneum
      upon adhesions and demonstrate its reduction by oxygen, strongly suggesting that
      the main cause of adhesion formation is the relatively superficial hypoxaemia
      produced by the pneumoperitoneum.

PMID- 10920100
TI  - Development of a novel glucose polymer solution (icodextrin) for adhesion
      prevention: pre-clinical studies.
AB  - Intra-abdominal adhesion formation causes significant post-operative morbidity.
      Controlled studies using animal models have been carried out to assess the
      tolerability and preventive efficacy of icodextrin solution (a biodegradable,
      biocompatible, glucose polymer). Reduction of adhesion formation was first
      evaluated in a rabbit double uterine horn model, applying 10-75 ml of 7.5 and
      20%, or 50 ml of 2.5-20% icodextrin solution post-operatively. Significant
      increases in adhesion free sites (P < 0.005) were observed with volumes > or =25
      ml, and at concentrations > or =4%. Efficacy of 50 ml 4 and 20% icodextrin was
      then evaluated both during and after surgery, demonstrating significant
      reductions in adhesion formation (P < 0. 002). In one study, intra- plus post
      operative use of 4% icodextrin produced the greatest reduction of non-surgical
      site adhesions; in others, the post-operative effect was predominant. Post
      surgical administration of 50 ml 4% icodextrin in a rabbit sidewall model also
      resulted in more adhesion-free animals, and a significant reduction (P < 0.001)
      in areas of adhesion formation and reformation. In a rat infection potentiation
      model, 4% icodextrin produced no difference in mortality, abscess formation or
      overall abscess score. These data suggest that 4% icodextrin offers a well
      tolerated and effective means of reducing post-surgical adhesion formation.

PMID- 10920101
TI  - Operative hysteroscopy for infertility using normal saline solution and a coaxial
      bipolar electrode: a pilot study.
AB  - The efficacy and safety of a coaxial bipolar electrode surgical system used to
      treat surgically remediable infertility conditions was investigated. After
      gaining initial experience with 50 patients with perimenopausal menorrhagia, 40
      infertile patients with submucous myomas (n = 12), uterine septum (n = 12),
      uterine adhesions (n = 11), and uterine hypoplasia (n = 5) were treated. Bipolar
      electrodes were inserted through a '5' French operating channel of a 5.5 mm
      hysteroscope without cervical dilatation. Three electrodes were used: ball,
      twizzle and spring. Power settings ranged from 50 W (desiccation mode) to 200 W
      (vapour cut mode). Normal saline was used as the distension medium. All the
      procedures were completed within 30 min using a 1 l bag of normal saline
      solution. No episodes of cervical laceration, uterine perforation, haemorrhage,
      fluid overload or thermal injury occurred. Mild cramping, vaginal bleeding and
      vaginal discharge were common during the first week. No patients were readmitted.
      This new surgical approach appears to be well tolerated, safe, and is an
      effective alternative to conventional hysteroscopic surgery in the treatment of
      intrauterine lesions.

PMID- 10920102
TI  - Comparison between day-2 embryos obtained either from ICSI or resulting from
      short insemination IVF: influence of maternal age.
AB  - Short incubation time prevents deleterious effects of cumulus cell degeneration
      and excess spermatozoa in IVF embryos. We performed a short incubation (3 h)
      protocol in 328 IVF cycles, in order to compare the developmental potential of
      regular IVF embryos with those originating from 316 cycles entered our
      intracytoplasmic sperm injection (ICSI) programme over the same period. Embryo
      transfers were performed in all patients on day 2. The mean number of embryos
      transferred was 1.92 for the ICSI group and 1.73 for the IVF group (P < 0.007).
      This was related only to the wishes of patients. However, the policy of the
      centre is to transfer a low number of embryos in young patients in order to avoid
      multiple pregnancies. All spare embryos were permitted to grow to the blastocyst
      stage for freezing. Shortening incubation time did not decrease fertilization
      rates. In our overall population, no difference was observed in the implantation
      rates per embryo for IVF (19%) or for ICSI (20%). An age-related decrease in
      embryo production was observed for both groups of patients (P < 0.01 for ICSI and
      P < 0.001 for IVF). The age-related decrease in embryo implantation was only
      significant for the IVF group (P < 0.03 for patients <30 and >35 years of age). A
      significant overall decrease in blastocyst formation was observed for spare
      embryos after ICSI versus IVF (34.2 versus 43.8%; P < 0. 05). The significance of
      this observation is discussed.

PMID- 10920103
TI  - Chromosome mosaicism in day 3 aneuploid embryos that develop to morphologically
      normal blastocysts in vitro.
AB  - In all, 143 human embryos obtained 3 days (day 3) after insemination or
      intracytoplasmic sperm injection (ICSI) were biopsied and a single nucleated cell
      removed for identification of aneuploidy by fluorescent in-situ hybridization
      (FISH) for chromosomes X, Y, 13, 16, 18 and 21. Fifty-one per cent of embryos
      were aneuploid and significantly more aneuploid embryos blocked in further
      development to morulae and blastocysts than euploid embryos (59 versus 34%; P <
      0.001). Chromosomal analysis of the generated blastocysts revealed 40% were
      aneuploid (16 of 40 generated blastocysts). Re-examination of cells by FISH for
      the same chromosome probes of the inner cell mass (ICM) of expanded and hatching
      blastocysts derived from the aneuploid embryos revealed a high incidence of
      mosaicism of ICM cell lineages that were usually predictable from observations of
      day 3 single-cell biopsies. These data would not support the hypothesis of a
      preferential allocation of euploid cells to the ICM and aneuploid cells to the
      trophectoderm. A high concordance between day 3 aneuploidy diagnosis and ICM cell
      lineages was observed with trisomies (97%), and multiple complex chromosome
      numerical abnormalities (100%). A reduced concordance was observed with
      monosomies (65%) and haploidy (18%). Concomitantly, the proportion of ICM cell
      lineages was increased in blastocysts whose chromosomal condition was diagnosed
      as haploid (21%) or with complex numerical abnormalities (50%).

PMID- 10920104
TI  - Ultra-rapid freezing of human multipronuclear zygotes using electron microscope
      grids.
AB  - Developmental capacity of human multipronuclear (PN) zygotes cryopreserved using
      an ultra-rapid freezing method and electron microscope (EM) grids was studied.
      Multipronuclear zygotes obtained from a human IVF programme were used as an
      alternative to normal 2PN zygotes; they were divided into 3PN or >or =4PN zygotes
      and their in-vitro development and cryo-injury were compared according to PN
      number. EFS30, which consisted of 30% ethylene glycol, 18% Ficoll, 0. 5 mol/l
      sucrose and 10% fetal bovine serum with added modified Dulbecco's phosphate
      buffered saline was used as the freezing solution. After ultra-rapid freezing and
      thawing 85.5% of multipronuclear zygotes survived. A comparison of cleavage rates
      between the control and cryopreserved groups showed no significant difference
      (3PN; 81.3 and 85.4% and > or =4PN; 90.0 and 95.7% respectively). Comparing the
      in-vitro development after thawing up to blastocyst formation on day 5 after IVF,
      the outcome of the frozen 3PN group (22.0%) was not different from that of
      control 3PN group (38.5%), while the outcome of the frozen > or =4PN group (4.5%)
      was significantly lower than that of control > or =4PN group (44.4%) (P < 0.05).

PMID- 10920105
TI  - IVF of mouse ova in a simplex optimized medium supplemented with amino acids.
AB  - The addition of amino acids to a modified simplex optimized medium (mKSOM) did
      not increase the percentage of blastocysts that develop from CF1 mouse ova
      fertilized in vitro. In contrast, the percentage of blastocysts that began to
      hatch and the number of cells in these blastocysts, particularly in the inner
      cell mass, was increased. The added amino acids also supported the development of
      a more organized extracellular matrix in the same blastocysts. The results
      suggest that zygotes produced in amino acid-supplemented mKSOM have a greater
      developmental potential, perhaps developing at a faster rate, than zygotes
      produced in mKSOM. This enhanced developmental potential may be caused by the
      alleviation of osmotic stress on the ova and zygotes by the amino acids that are
      osmolytes. The fertilization of human ova in vitro may benefit from the inclusion
      of free amino acids in the fertilizing medium. The availability of a medium that
      can be used to support both IVF and preimplantation development in the mouse is
      likely to benefit the recovery of mouse strains from cryopreserved spermatozoa.

PMID- 10920106
TI  - Successful pregnancy following blastocyst vitrification: case report.
AB  - A 32 year old woman and her 32 year old spouse were referred to our IVF
      programme. Following recovery of 12 mature oocytes, nine were fertilized
      following conventional IVF. Three fresh embryos were transferred to the uterus,
      but all failed to result in pregnancy. Six supernumerary embryos were cultured in
      vitro until day 5 in order to create blastocysts. Two grew to the blastocyst
      stage and were vitrified using a modification of a previous method. Two
      blastocysts survived the freeze-thaw process and were transferred to the
      patient's uterus during a natural cycle, 3 months after the previous retrieval
      cycle. Implantation resulted in a healthy pregnancy; delivery is expected in June
      2000. This report documents the first successful pregnancy in Japan, achieved via
      blastocyst vitrification.

PMID- 10920107
TI  - A 47,XXY fetus conceived after ICSI of spermatozoa from a patient with non-mosaic
      Klinefelter's syndrome: case report.
AB  - The birth of 12 healthy infants to fathers with non-mosaic Klinefelter's syndrome
      has been reported so far. The spermatozoa for these pregnancies was obtained from
      frozen-thawed ejaculate in one pregnancy (twins) and from the testis in the
      remaining 10 infants. All of them had a normal karyotype. We describe a patient
      with non-mosaic Klinefelter's syndrome from whom a testicular biopsy was obtained
      and motile spermatozoa were collected. Of 16 oocytes that were injected, 14
      fertilized and cleaved. Three embryos were transferred, resulting in a triplet
      pregnancy. Karyotype analysis from chorionic villous sampling revealed 46,XX,
      46,XY and 46,XXY from the three fetuses. The affected 46,XXY fetus was reduced on
      the 14th gestational week. The pregnancy culminated with the birth of a healthy
      male and female, on the 36th gestational week, weighing 3600 and 2660 g
      respectively. This case report proves the presence of hyperploid spermatozoa in
      the seminiferous lumen, and strengthens the necessity of genetic diagnosis of the
      embryos or fetuses in such pregnancies to fathers with non-mosaic Klinefelter's
      syndrome.

PMID- 10920108
TI  - Increased HLA-DR homozygosity associated with pre-eclampsia.
AB  - It is generally accepted that maternal recognition of paternally derived fetal
      antigens occurs during normal pregnancy and may be beneficial for implantation
      and maintenance of gestation. Thus, we have investigated the human leukocyte
      class II DR antigens (HLA-DR), whose role in self and non-self recognition is
      well known, in women with pre-eclampsia, their partners and in control couples.
      The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their
      partners and 70 healthy control couples using the serological Terasaki technique.
      Our results did not show any particular HLA-DR antigen to be correlated with pre
      eclampsia, but a statistically significant increase of only one identifiable HLA
      DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in
      the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control
      couples (P < 0.000001). The analysis of HLA-DR compatibility between pre
      eclamptic women and their partners showed a statistically highly significant
      increase of the female-to-male compatibility (P = 0.0003) and a lower but
      significant male-to-female compatibility in comparison with controls (P = 0.014).
      From our results, it emerges that HLA-DR homozygosity and reduced antigenic
      disparity seem to be associated to a major risk for pre-eclampsia, which
      consequently appears to be a 'couple's disease'.

PMID- 10920109
TI  - Analysis of mid-trimester corticotrophin-releasing hormone and alpha-fetoprotein
      concentrations for predicting pre-eclampsia.
AB  - The aims of this study were firstly to examine if corticotrophin-releasing
      hormone (CRH) concentrations in maternal plasma were significantly elevated in
      Chinese pregnancies complicated by pre-eclampsia, secondly to assess if this
      elevation could be detected in the mid-trimester before onset of clinical signs
      of the disease, and thirdly to evaluate the performance of using maternal CRH
      and/or alpha-fetoprotein (AFP) concentrations in the mid-trimester for prediction
      of pre-eclampsia. The first part of this study was tested in a cohort of 39
      subjects. The CRH concentrations were significantly elevated in pregnant women
      complicated by pre-eclampsia. The second and third parts of the study involved a
      different cohort of 1021 subjects. Both CRH and AFP concentrations in the mid
      trimester were significantly elevated in those who subsequently developed pre
      eclampsia. However, when used for prediction of pre-eclampsia, neither the CRH
      nor AFP concentrations alone in the mid-trimester had strong predictive value.
      Although the combination of both tests improved the detection rate compared to
      the use of CRH alone, the small increase in the likelihood ratio from 1.9 to 2.6
      did not suggest that the combination would be of great clinical value.

PMID- 10920110
TI  - Obstetric outcome of singleton pregnancies after IVF: a matched control study in
      four Dutch university hospitals.
AB  - In singleton pregnancies after IVF a high rate of preterm deliveries and an
      increased rate of small-for-gestational age (SGA) children in comparison to the
      general parturient population have been reported. However, due to differences
      between IVF mothers and their peers who conceived naturally, careful selection of
      the control group is necessary to assess whether IVF pregnancies really carry
      increased risks of adverse outcome. In our study 307 IVF pregnancies were
      compared with 307 control pregnancies after elaborate matching for an extensive
      number of maternal characteristics, as well as for the hospital that provided the
      obstetric care. Four Dutch university hospitals contributed to the study. In
      cases with spontaneous onset of labour, gestational age at delivery was 3 days
      shorter in the IVF group (275 versus 278 days, P = 0.05). The proportion of SGA
      was higher in the IVF group (16.2 versus 7.9%, P < 0.001). The combination of
      these two results denotes a distinct difference between IVF and control
      pregnancies. Placental weight was comparable in both groups.

PMID- 10920111
TI  - Impaired glucose tolerance and pregnancy outcome in Chinese women with high body
      mass index.
AB  - To determine if impaired glucose tolerance (IGT) impacts on the outcome of
      singleton pregnancies in Chinese women with a high (>26 kg/m(2)) body mass index
      (BMI), a retrospective case-control study was performed on 128 women with IGT and
      128 controls with normal oral glucose tolerance test results, who were matched
      for pre-pregnancy BMI (within 0.1 kg/m(2)) and delivered within the same 3 year
      period. The IGT group was older, with more multiparae, a higher incidence of
      previous gestational diabetes mellitus, higher booking haemoglobin and fasting
      glucose concentrations, but no difference in the pre-pregnancy weight,
      gestational weight gain, or weight or BMI at delivery. There was no difference in
      the obstetric complications, mode of delivery, or the gestational age or mean
      infant birthweight. However, the birthweight ratio (relative to mean birthweight
      for gestation), incidence of large-for-gestational-age (birthweight >90th
      percentile) and macrosomic (birthweight > or =4000 g) infants, and treatment for
      neonatal jaundice, were significantly higher in the IGT group. The results
      suggest that some of the complications attributed to gestational diabetes
      mellitus are probably related to maternal weight excess/obesity in the affected
      subjects, but IGT could still affect infant birthweight outcome despite diet
      treatment which has normalized gestational weight gain.

PMID- 10920112
TI  - Do placental lesions reflect thrombophilia state in women with adverse pregnancy
      outcome?
AB  - We examined the relationship between placental histology and thrombophilia status
      in women who were admitted with severe pre-eclampsia/eclampsia, placental
      abruption, intrauterine growth restriction or unexplained stillbirth. All women
      had thrombophilia screen at least 10 weeks after delivery (antithrombin III,
      protein C, protein S, activated protein C resistance, anticardiolipin antibodies,
      lupus anticoagulant, fasting plasma homocysteine and specific mutations to
      methylenetetrahydrofolate reductase C677T, G20210A prothrombin gene and factor V
      Leiden. Placental histology reports were examined to identify the frequency of
      thrombotic lesions in the placenta including fetal stem vessel thrombosis, fetal
      thrombotic vasculopathy, placental infarction, perivillous fibrin deposition,
      intervillous thrombosis and placental floor infarction. During a 17 month period,
      a cohort of 79 women met the study criteria. Thirty (70%) out of 43 women with
      abnormal thrombophilia screen had abnormal placental histology. Twenty-eight
      (78%) out of 36 women with negative thrombophilia screen had abnormal placentae.
      No specific histological pattern could be identified when thrombophilia positive
      and thrombophilia negative groups were compared. We propose that there is a poor
      correlation between thrombophilia status and pathological changes of the placenta
      in women with severe pregnancy complications.

PMID- 10920113
TI  - The feto-placental unit stimulates the pregnancy-associated increase in maternal
      bone metabolism.
AB  - The aim of the study was to investigate role of the feto-placental unit in the
      pregnancy-induced increase in maternal bone metabolism. To achieve this,
      circulating concentrations of carboxy terminal pro-peptide of type I pro-collagen
      (PICP, a marker of bone formation) and cross-linked carboxy terminal telopeptide
      of type I collagen (ICTP, a marker of bone resorption) were measured in three
      groups of pregnant women. Group 1 comprised 12 women with singleton pregnancies;
      group 2, nine women with twin pregnancies; and group 3, 19 women with multifetal
      pregnancies (> or =3 fetuses) before and after selective fetal reduction to twin
      pregnancies. Blood samples were obtained at 10-12 weeks gestation (groups 1-3,
      pre-fetal reduction in group 3) and 4 weeks and 8 weeks later (groups 2 and 3).
      Before fetal reduction there was a significant correlation between the number of
      fetuses and the concentrations of both PICP and ICTP (r = 0.503 and P = 0.001 and
      r = 0.573 and P < 0.001 respectively). The circulating concentrations of PICP and
      ICTP were significantly higher in the pre-reduction multifetal pregnancies than
      in the twin pregnancies (P < 0.001 and P = 0.0013 respectively). The circulating
      concentrations of ICTP in multifetal pregnancies fell by 4 weeks after fetal
      reduction to those observed in control twins. Concentrations of PICP were
      unaltered after fetal reduction. Higher order multiple pregnancies had the
      greatest decline in ICTP concentrations. These data suggest that the increased
      bone turnover observed in the multifetal pregnancies is due to a factor derived
      from the feto-placental unit and that this factor acts primarily to stimulate
      bone resorption.

PMID- 10920114
TI  - Inhibition of nitric oxide synthesis causes preterm delivery in the mouse.
AB  - The aim of the present study was to investigate whether an inhibitor of nitric
      oxide (NO) synthesis provokes preterm delivery in a mouse model. ICR (CD-1) mice
      were injected s.c. with N(G)-nitro-L-arginine methyl esther (L-NAME) at 0, 40, 70
      or 100 mg/kg on gestation day (GD) 15.5 and 16. Delivery was considered preterm
      if it occurred before GD 18. In a satellite study, the potential ability of the
      NO donor sodium nitroprusside (SNP) to prevent L-NAME-induced preterm delivery
      was tested. Five hours before the initiation of treatment regimen with L-NAME at
      70 mg/kg, mice were implanted s.c. with micro-osmotic pumps infusing SNP at 0 or
      10 microg/kg/min continuously for 3 days. Administration of L-NAME evoked preterm
      delivery. This response was noted in 64 and 60% of animals treated with 70 and
      100 mg/kg L-NAME respectively (P < 0.05 versus control value). Infusion with SNP
      provided complete and significant (P < 0. 05 versus positive control value)
      protection from L-NAME-initiated preterm delivery. This is the first report to
      reveal that an inhibitor of NO synthesis initiates preterm delivery in a mouse
      model.

PMID- 10920115
TI  - Third trimester iron status and pregnancy outcome in non-anaemic women; pregnancy
      unfavourably affected by maternal iron excess.
AB  - A prospective observational study was performed on 488 women with haemoglobin
      >/=10 g/dl at booking to examine the relationship between serum ferritin
      concentration quartiles at 28-30 weeks gestation with maternal characteristics,
      pregnancy complications and infant outcome. While there was no difference in the
      maternal characteristics or gestational age, the infant size decreased
      significantly and progressively from the lowest to the highest quartile. Despite
      a significant difference in the incidence of multiparous women, there was no
      difference in the incidence of most complications except for prelabour rupture of
      the membranes and infant admission to the neonatal unit. Compared with the other
      three quartiles, the highest quartile was associated with increased risk for
      preterm delivery and neonatal asphyxia, while the lowest quartile was associated
      with decreased risk of pre-eclampsia, prelabour rupture of the membranes, and
      infant admission to the neonatal unit. Overall, ferritin quartiles were
      correlated with other parameters of iron status and red cell indices, and
      ferritin concentration was inversely correlated with infant birthweight. Our
      findings suggested that maternal ferritin concentration is primarily a reflection
      of maternal iron status, and a high level is associated with unfavourable
      outcome. The rationale of routine iron supplementation in non-anaemic women needs
      to be re-examined.

PMID- 10920116
TI  - The importance of a genetic link in mothers commissioning a surrogate baby in the
      UK.
AB  - Reproductive technologies have enabled genetic and gestational links between
      parents and children to become separate from social relationships and inter
      personal ties within families. The meaning of family is discussed, by drawing on
      research with infertile women who become parents as the result of surrogacy. The
      complexities of family are highlighted by addressing the consequences of babies
      carried and delivered by women who are not the biological parents of the child,
      or by women who are the biological mother of the child but who relinquish their
      genetic material to another woman. In all, 29 women completed a questionnaire on
      various aspects of their infertility, surrogacy, and the importance of a genetic
      link. The study identified some characteristics of women who have become mothers
      as a result of surrogacy, and some of their reactions to this way of creating
      families. In general, women who could use their own genetic material tended to
      believe a genetic link was important. Those who could not use their own genetic
      material were less uniform in their beliefs about the importance of a genetic
      link. The cognitive dissonance observed in this population has implications for
      the future of reproductive technology assisting couples in becoming a family with
      or without genetic relatedness.

PMID- 10920117
TI  - Multiple gestation pregnancy. The ESHRE Capri Workshop Group.
AB  - Multiple gestation pregnancy rates are high in assisted reproductive treatment
      cycles because of the perceived need to stimulate excess follicles and transfer
      excess embryos in order to achieve reasonable pregnancy rates. Perinatal
      mortality rates are, however, 4-fold higher for twins and 6-fold higher for
      triplets than for singletons. Since the goal of infertility therapy is a healthy
      child, and multiple gestation puts that goal at risk, multiple pregnancy must be
      regarded as a serious complication of assisted reproductive treatment cycles. The
      1999 ESHRE Capri Workshop addressed the psychological, medical, social and
      financial implications of multiple pregnancy and discussed how it might be
      prevented. Multiple gestations are high risk pregnancies which may be complicated
      by prematurity, low birthweight, pre-eclampsia, anaemia, postpartum haemorrhage,
      intrauterine growth restriction, neonatal morbidity and high neonatal and infant
      mortality. Multiple gestation children may suffer long-term consequences of
      perinatal complications, including cerebral palsy and learning disabilities. Even
      when the babies are healthy they must share their parents' attention and may
      experience slow language development and behavioural problems. Current data
      indicate that the average hospital cost per multiple gestation delivery is
      greater than the average cost of in-vitro fertilization (IVF) and
      intracytoplasmic sperm injection (ICSI) cycles. Prevention is the most important
      means of decreasing multiple gestation rates. Multiple gestation rates in
      ovulation induction and superovulation cycles can be reduced by using lower
      dosage gonadotrophin regimens. If there are more than three mature follicles, the
      cycle should be converted to an IVF cycle, or it should be cancelled and
      intercourse should be avoided. In IVF cycles two embryos can be transferred
      without reducing birth rates in most circumstances. Embryo reduction involves
      extremely difficult decisions for infertile couples and should be used only as a
      last resort. Assisted reproductive treatment centres and registries should
      express cycle results as the proportion of singleton live births; twin and
      triplet rates should be reported separately as complications of the procedures.
      Reducing the multiple gestation pregnancy rate should be a high priority for
      assisted reproductive treatment programmes, despite the pressure from some
      patients to transfer more embryos in order to improve success. If nothing is
      done, public concern may lead to legislation in many countries, a step that would
      be unnecessary if assisted reproductive treatment programmes and registries took
      suitable steps to reduce multiple pregnancy rates.

PMID- 10920118
TI  - Continuation rates for oral contraceptives and hormone replacement therapy. The
      ESHRE Capri Workshop Group.
AB  - Despite the safety and effectiveness of low oestrogen-dose oral contraceptives
      (OC) and postmenopausal hormone replacement there is poor continuity of use of
      these agents by women. Patterns of use and the reasons affecting different
      frequencies of use in different countries are presented. Continuity and
      discontinuation rates are difficult to assess accurately but it is believed that
      the main reasons why women discontinue use of these agents are concerns about
      their perceived health risks and the presence of, or fear of, adverse clinical
      effects, particularly unscheduled uterine bleeding and weight gain. More
      information is needed about OC continuation rates in order to improve the
      acceptability of these safe, effective agents. Most women discontinue use of
      postmenopausal hormonal replacement within 2 years of initiating the therapy.
      Reasons include disappearance of symptoms of oestrogen deficiency, lack of
      awareness of health benefits of oestrogen, presence of side-effects (such as
      breast tenderness and weight gain), presence of uterine bleeding and increasing
      age. Suggestions to increase continuation of OC include extensive individual
      pretreatment counselling with a different emphasis in different age groups,
      education at the time of follow-up visits and telephone calls, and extensive use
      of educational aids such as brochures, pamphlets and audio tapes, and improvement
      of pharmaceutical packaging information. In conclusion there is an urgent need to
      assess the value of these strategies by long-term large controlled studies.

PMID- 10920119
TI  - Laparascopic management of a unicornuate uterus with two cavitated, non
      communicating rudimentary horns.

PMID- 10920120
TI  - Regarding recall bias in the association between idiopathic premature ovarian
      failure and fragile X premutation.

PMID- 10920121
TI  - Antiphospholipid antibodies and reproductive failure.

PMID- 10920122
TI  - Hypotriploid tripronuclear oocytes with two polar bodies obtained after ICSI: is
      irregular chromatid segregation involved?

PMID- 10920124
TI  - Appointment of new editor-in-chief

PMID- 10920125
TI  - Sentinel lymph node procedure in squamous cell carcinoma of the vulva.

PMID- 10920126
TI  - Retinoic acid receptor-beta as a prognostic indicator in stage I non-small-cell
      lung cancer.
AB  - PURPOSE: Retinoids are pivotal in the growth and differentiation of certain
      epithelial tissues, interacting with nuclear retinoid receptors (the retinoic
      acid receptors [RARs] and retinoid X receptors [RXRs]), which function as
      transcription factors. RAR-beta mRNA is undetectable by in situ hybridization
      (ISH) in 50% of non-small-cell lung cancers (NSCLC). RAR-beta may suppress
      tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-beta
      gene in stage I NSCLC is a prognostic factor of a poor clinical outcome. PATIENTS
      AND METHODS: We retrospectively analyzed RAR-beta mRNA levels (by ISH using a
      digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive
      patients with completely resected clinical/radiographic stage I NSCLC for whom
      clinical follow-up data were available. RESULTS: One hundred fifty-six patients
      who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha
      mRNA (used as a control to assess RNA degradation) and who had adequate follow-up
      could be evaluated. RAR-beta mRNA expression was undetectable in 51 patients,
      weakly positive in 64 patients, and strongly positive in 41 patients. Overall
      survival of the 41 patients with strongly positive RAR-beta was significantly
      worse than for the 115 patients with weak or absent RAR-beta (P =.045).
      CONCLUSION: Unexpectedly, strong RAR-beta expression was associated with a
      significantly worse outcome of early-stage NSCLC. The mechanisms underlying this
      clinically and biologically important finding should be further explored.

PMID- 10920127
TI  - Evaluating the financial impact of clinical trials in oncology: results from a
      pilot study from the Association of American Cancer Institutes/Northwestern
      University clinical trials costs and charges project.
AB  - PURPOSE: Medical care for clinical trials is often not reimbursed by insurers,
      primarily because of concern that medical care as part of clinical trials is
      expensive and not part of standard medical practice. In June 2000, President
      Clinton ordered Medicare to reimburse for medical care expenses incurred as part
      of cancer clinical trials, although many private insurers are concerned about the
      expense of this effort. To inform this policy debate, the costs and charges of
      care for patients on clinical trials are being evaluated. In this Association of
      American Cancer Institutes (AACI) Clinical Trials Costs and Charges pilot study,
      we describe the results and operational considerations of one of the first
      completed multisite economic analyses of clinical trials. METHODS: Our pilot
      effort included assessment of total direct medical charges for 6 months of care
      for 35 case patients who received care on phase II clinical trials and for 35
      matched controls (based on age, sex, disease, stage, and treatment period) at
      five AACI member cancer centers. Charge data were obtained for hospital and
      ancillary services from automated claims files at individual study institutions.
      The analyses were based on the perspective of a third-party payer. RESULTS: The
      mean age of the phase II clinical trial patients was 58.3 years versus 57.3 years
      for control patients. The study population included persons with cancer of the
      breast (n = 24), lung (n = 18), colon (n = 16), prostate (n = 4), and lymphoma (n
      = 8). The ratio of male-to-female patients was 3:4, with greater than 75% of
      patients having stage III to IV disease. Total mean charges for treatment from
      the time of study enrollment through 6 months were similar: $57,542 for clinical
      trial patients and $63,721 for control patients (1998 US$; P =.4) CONCLUSION:
      Multisite economic analyses of oncology clinical trials are in progress.
      Strategies that are not likely to overburden data managers and clinicians are
      possible to devise. However, these studies require careful planning and
      coordination among cancer center directors, finance department personnel,
      economists, and health services researchers.

PMID- 10920129
TI  - Locoregional recurrence patterns after mastectomy and doxorubicin-based
      chemotherapy: implications for postoperative irradiation.
AB  - PURPOSE: The objective of this study was to determine locoregional recurrence
      (LRR) patterns after mastectomy and doxorubicin-based chemotherapy to define
      subgroups of patients who might benefit from adjuvant irradiation. PATIENTS AND
      METHODS: A total of 1,031 patients were treated with mastectomy and doxorubicin
      based chemotherapy without irradiation on five prospective trials. Median follow
      up time was 116 months. Rates of isolated and total LRR (+/- distant metastasis)
      were calculated by Kaplan-Meier analysis. RESULTS: The 10-year actuarial rates of
      isolated LRR were 4%, 10%, 21%, and 22% for patients with zero, one to three,
      four to nine, or >/= 10 involved nodes, respectively (P <.0001). Chest wall (68%)
      and supraclavicular nodes (41%) were the most common sites of LRR. T stage (P
      <.001), tumor size (P <.001), and >/= 2-mm extranodal extension (P <.001) were
      also predictive of LRR. Separate analysis was performed for patients with T1 or
      T2 primary disease and one to three involved nodes (n = 404). Those with fewer
      than 10 nodes examined were at increased risk of LRR compared with those with >/=
      10 nodes examined (24% v 11%; P =.02). Patients with tumor size greater than 4.0
      cm or extranodal extension >/= 2 mm experienced rates of isolated LRR in excess
      of 20%. Each of these factors continued to significantly predict for LRR in
      multivariate analysis by Cox logistic regression. CONCLUSION: Patients with
      tumors >/= 4 cm or at least four involved nodes experience LRR rates in excess of
      20% and should be offered adjuvant irradiation. Additionally, patients with one
      to three involved nodes and large tumors, extranodal extension >/= 2 mm, or
      inadequate axillary dissections experience high rates of LRR and may benefit from
      postmastectomy irradiation.

PMID- 10920128
TI  - Sentinel lymph node procedure is highly accurate in squamous cell carcinoma of
      the vulva.
AB  - PURPOSE: To determine the diagnostic accuracy of the sentinel lymph node
      procedure in patients with squamous cell carcinoma of the vulva and to
      investigate whether step sectioning and immunohistochemistry of sentinel lymph
      nodes increase the sensitivity for detection of metastases. PATIENTS AND METHODS:
      Between July 1996 and July 1999, 59 patients with primary vulvar cancer were
      entered onto a two-center prospective study. All patients underwent sentinel
      lymph node procedure with the combined technique (preoperative lymphoscintigraphy
      with technetium-99m-labeled nanocolloid and intraoperative blue dye). Radical
      excision of the primary tumor with uni- or bilateral inguinofemoral
      lymphadenectomy was performed subsequently. Sentinel lymph nodes and
      lymphadenectomy specimens were sent for histopathologic examination separately.
      Sentinel lymph nodes, negative at the time of routine pathologic examination,
      were re-examined with step sectioning and immunohistochemistry. RESULTS: In 59
      patients, 107 inguinofemoral lymphadenectomies were performed (11 unilateral and
      48 bilateral). All sentinel lymph nodes, as observed on preoperative
      lymphoscintigram, were identified successfully intraoperatively. Routine
      histopathologic examination showed lymph node metastases in 27 groins, all of
      which were detected by the sentinel lymph node procedure. The negative predictive
      value for a negative sentinel lymph node was 100% (97.5% confidence interval
      [CI], 95% to 100%). Step sectioning and immunohistochemistry showed four
      additional metastases in 102 sentinel lymph nodes (4%; 95% CI, 1% to 9%) that
      were negative at the time of routine histopathologic examination. CONCLUSION:
      Sentinel lymph node procedure with the combined technique is highly accurate in
      predicting the inguinofemoral lymph node status in patients with early-stage
      vulvar cancer. Future trials should focus on the safe clinical implementation of
      the sentinel lymph node procedure in these patients. Step sectioning and
      immunohistochemistry slightly increase the sensitivity of detecting metastases in
      sentinel lymph nodes and should be included in these trials.

PMID- 10920130
TI  - Relationship between tumor location and relapse in 6,781 women with early
      invasive breast cancer.
AB  - PURPOSE: To explore the independent prognostic impact of medial hemisphere tumor
      location in early breast cancer. PATIENTS AND METHODS: A comprehensive database
      was used to review patients referred to the British Columbia Cancer Agency from
      1989 to 1995 with early breast cancer. Patients were grouped according to relapse
      risk (high or nonhigh) and adjuvant systemic therapy received. Multiple
      regression analysis was used to determine whether the significance of primary
      tumor location (medial v lateral hemisphere) was independent of known prognostic
      factors and treatment. RESULTS: In the adjuvant systemic therapy groups, medial
      location was associated with a 50% excess risk of systemic relapse and breast
      cancer death compared with lateral location. Five-year systemic disease-free
      survival rates were 66.3% and 74.2% for high-risk medial and lateral lesions,
      respectively (P <.005). Corresponding 5-year disease-specific survival rates were
      75.7% and 80.8%, respectively (P <.03). No significant differences were observed
      between medial and lateral location for low-risk disease regardless of adjuvant
      therapy or for high-risk disease with no adjuvant therapy. Local recurrence rates
      were similar for all risk and therapy groups. CONCLUSION: The two-fold risk of
      relapse and breast cancer death associated with high-risk medial breast tumors
      may be due to occult spread to internal mammary nodes (IMNs). Enhanced local
      control, such as with irradiation of the IMN chain, may be one way to reduce the
      excess risk. Ongoing randomized controlled trials may provide prospective answers
      to the question of the optimal volume of radiotherapy.

PMID- 10920131
TI  - Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: a
      population-based study.
AB  - PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy,
      especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS:
      We performed a population-based study in a cohort of 3,093 women younger than 85
      years who resided in the French administrative area of the Cote d'Or, who were
      given a first diagnosis of primary breast cancer between 1982 and 1996, and who
      received a curative treatment. Information about therapy and follow-up events was
      obtained from records of cancer registries that covered this area. RESULTS: Until
      December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia
      and refractory anemia with excess of blasts, occurred in patients before any
      local or distant recurrence. All cases developed in the first 4 years of follow
      up. Compared with the general female population, the incidence rate of leukemia
      was significantly increased in women who received radiotherapy and chemotherapy
      (standardized incidence ratio, 28.5; P <.0001). A dose-dependent increase in the
      risk of leukemia was observed in women treated with mitoxantrone. Cox regression
      analysis showed that the risk of leukemia was significantly lower in patients
      treated with anthracyclines than in those treated with mitoxantrone at cumulative
      doses >/= 13 mg/m(2). CONCLUSION: The combination of adjuvant radiotherapy and
      chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients
      with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines
      cannot be ruled out with certainty. However, there are some suggestions that
      these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone
      and could be preferred in an adjuvant setting.

PMID- 10920132
TI  - High-producer haplotypes of tumor necrosis factor alpha and lymphotoxin alpha are
      associated with an increased risk of myeloma and have an improved progression
      free survival after treatment.
AB  - PURPOSE: To determine the effect of polymorphic variations in the tumor necrosis
      factor alpha (TNFalpha) and lymphotoxin alpha (LTalpha) genes on the
      predisposition to myeloma and the effect of these polymorphisms on response to
      treatment and overall survival. PATIENTS AND METHODS: Genotype distribution was
      determined in 63 patients with monoclonal gammopathy of uncertain significance
      (MGUS) and 198 patients with myeloma and compared with that in 250 age- and sex
      matched population-based controls. The effect on treatment response and survival
      was determined in 171 myeloma patients treated with either conventional or high
      dose chemotherapy. RESULTS: Comparison of the extended TNFalpha/LTalpha haplotype
      in the myeloma cases and controls showed a significant excess of high-producer
      alleles in the cases. The double heterozygotes TNF1/2 and LT10.5/5.5 were present
      in 35.8% of cases but in only 18% of the controls; this presence was associated
      with a significant increased risk of myeloma (odds ratio, 2.05; 95% confidence
      interval, 1.26 to 3.35). A similar odds ratio was seen in the MGUS cases,
      suggesting that this genotype is associated with the initiation of plasma-cell
      disorders rather than the progression of MGUS to myeloma. The median overall
      survival time of myeloma patients was 53.8 months and showed no difference with
      regard to TNFalpha/LTalpha polymorphic status. A trend toward an improved
      progression-free survival was apparent in cases with a high-producer haplotype,
      although this effect was seen only in patients receiving high-dose chemotherapy.
      CONCLUSION: Individuals with polymorphisms associated with a high production of
      TNFalpha/LTalpha are at a significantly increased risk of developing MGUS and
      myeloma. The impact of polymorphic status on overall survival is minimal,
      although there is a trend toward an increased progression-free survival in the
      high-producer group.

PMID- 10920133
TI  - Enhancement of platelet recovery after myelosuppressive chemotherapy by
      recombinant human megakaryocyte growth and development factor in patients with
      advanced cancer.
AB  - PURPOSE: To explore the influence of dose and schedule on the ability of
      pegylated recombinant human megakaryocyte growth and development factor (PEG
      rHuMGDF) to abrogate thrombocytopenia after multiple cycles of chemotherapy and
      to mobilize peripheral-blood progenitor cells (PBPC). PATIENTS AND METHODS: In
      this open-label study, 68 patients with advanced cancer were randomized to
      receive PEG-rHuMGDF subcutaneously at different doses and durations before
      administration of carboplatin 600 mg/m(2), cyclophosphamide 1,200 mg/m(2), and
      filgrastim 5 microgram/kg/d. PEG-rHuMGDF was not given after the first cycle of
      chemotherapy but was given after the second and subsequent cycles. Chemotherapy
      was given every 28 days for up to six cycles. RESULTS: In patients who received
      the same dose of chemotherapy for at least two cycles, the platelet nadir was
      significantly higher (47.5 x 10(9)/L v 35.5 x 10(9)/L; P =.003) and duration of
      grade 3 or 4 thrombocytopenia significantly shorter (0 v 3 days; P =.004) when
      PEG-rHuMGDF was administered after chemotherapy. There was no evidence of an
      effect of PEG-rHuMGDF when it was given before chemotherapy. Platelet recovery
      after the first cycle of chemotherapy was no different for different PEG-rHuMGDF
      regimens, and there was no difference between patients treated with PEG-rHuMGDF
      and historical controls treated with identical chemotherapy. There was a modest
      dose-related increase in progenitor cell levels after administration of PEG
      rHuMGDF alone. Peak levels of PBPC occurred later in cycle 2 than in cycle 1 but
      were not different in magnitude. CONCLUSION: PEG-rHuMGDF abrogated severe
      thrombocytopenia after dose-intensive chemotherapy. However, it had only a modest
      effect on progenitor cell levels and did not enhance progenitor cell mobilization
      after chemotherapy and filgrastim.

PMID- 10920134
TI  - Preoperative prediction of surgical margin status in patients with prostate
      cancer treated by radical prostatectomy.
AB  - PURPOSE: We sought to determine the preoperative factors associated with surgical
      margin status in patients who underwent radical prostatectomy for prostate
      cancer. PATIENTS AND METHODS: The study group consisted of 339 patients who were
      treated by radical retropubic prostatectomy and bilateral pelvic lymphadenectomy
      at the Mayo Clinic. None received preoperative adjuvant therapy. The mean age at
      the time of surgery was 66 years (range, 45 to 79 years). All specimens were
      totally embedded and whole-mounted. Positive surgical margin was defined as the
      presence of cancer cells at the inked margins. Numerous pathologic
      characteristics in needle biopsies and preoperative clinical findings were
      analyzed. RESULTS: The overall margin positivity rate was 24%. In univariate
      analysis, preoperative serum prostate-specific antigen (PSA) level, Gleason
      score, perineural invasion, percentage of cancer in the biopsy specimens, and
      number and percentage of biopsy cores involved by cancer were all associated with
      positive surgical margins. In multivariate analysis, preoperative serum PSA level
      (odds ratio for a doubling of PSA levels, 1.9; 95% confidence interval, 1.5 to
      2.4; P <.001) and percentage of cancer in the biopsy specimens (odds ratio for a
      10% increase, 1.3; 95% confidence interval, 1.2 to 1.4; P <.001) were predictive
      of margin status in radical prostatectomy. With use of preoperative serum PSA
      level and percentage of cancer in the biopsy as predictors of surgical margins,
      the overall accuracy as measured by the area under the receiver operating
      characteristic curve was 0.74. CONCLUSION: Preoperative serum PSA level and
      percentage of cancer in the biopsy specimens were independently associated with
      surgical margin status in patients who underwent radical prostatectomy for
      prostate cancer. The combination of these two factors provides a high level of
      predictive accuracy for margin status.

PMID- 10920135
TI  - Matched-pair analysis of conformal high-dose-rate brachytherapy boost versus
      external-beam radiation therapy alone for locally advanced prostate cancer.
AB  - PURPOSE: We performed a matched-pair analysis to compare our institution's
      experience in treating locally advanced prostate cancer with external-beam
      radiation therapy (EBRT) alone to EBRT in combination with conformal interstitial
      high-dose-rate (HDR) brachytherapy boosts (EBRT + HDR). MATERIALS AND METHODS:
      From 1991 to 1998, 161 patients with locally advanced prostate cancer were
      prospectively treated with EBRT + HDR at William Beaumont Hospital, Royal Oak,
      Michigan. Patients with any of the following characteristics were eligible for
      study entry: pretreatment prostate-specific antigen (PSA) level of >/= 10.0
      ng/mL, Gleason score >/= 7, or clinical stage T2b to T3c. Pelvic EBRT (46.0 Gy)
      was supplemented with three (1991 through 1995) or two (1995 through 1998)
      ultrasound-guided transperineal interstitial iridium-192 HDR implants. The
      brachytherapy dose was escalated from 5.50 to 10.50 Gy per implant. Each of the
      161 EBRT + HDR patients was randomly matched with a unique EBRT-alone patient.
      Patients were matched according to PSA level, Gleason score, T stage, and follow
      up duration. The median PSA follow-up was 2.5 years for both EBRT + HDR and EBRT
      alone. RESULTS: EBRT + HDR patients demonstrated significantly lower PSA nadir
      levels (median, 0.4 ng/mL) compared with those receiving EBRT alone (median, 1.1
      ng/mL). The 5-year biochemical control rates for EBRT + HDR versus EBRT-alone
      patients were 67% versus 44%, respectively (P <.001). On multivariate analyses,
      pretreatment PSA, Gleason score, T stage, and the use of EBRT alone were
      significantly associated with biochemical failure. Those patients in both
      treatment groups who experienced biochemical failure had a lower 5-year cause
      specific survival rate than patients who were biochemically controlled (84% v
      100%; P <.001). CONCLUSION: Locally advanced prostate cancer patients treated
      with EBRT + HDR demonstrate improved biochemical control compared with those who
      are treated with conventional doses of EBRT alone.

PMID- 10920136
TI  - First-line chemotherapy with local treatment can prevent external-beam
      irradiation and enucleation in low-stage intraocular retinoblastoma.
AB  - PURPOSE: To evaluate the efficacy of first-line chemotherapy (CT) in preventing
      external-beam radiotherapy (EBR) and/or enucleation in patients with
      retinoblastoma (Rbl). PATIENTS AND METHODS: Twenty-four patients with newly
      diagnosed unilateral or bilateral Rbl received CT associated with local treatment
      (LT). Two to five courses of etoposide and carboplatin were administered at 3- to
      4-week intervals, depending on tumor response, and were completed each time by
      LT. RESULTS: Tumor response was observed in all eyes. Twenty-one of 24 patients
      showed a complete response (CR) that persisted at a median follow-up (FU) of 31
      months (range, 4 to 41 months). Among the three patients who relapsed, two were
      lost to FU and one died of progressive disease. CR was achieved by CT and LT
      alone in 15 (71.4%) of 21 patients with less advanced disease (groups I to III).
      Six other patients with advanced disease (groups IV and V) experienced treatment
      failure and needed salvage treatment by EBR and/or enucleation. The difference
      between the two patient groups with regard to disease stage was statistically
      significant (P <.0001). EBR could be avoided in 13 (68.4%) of 19 patients, who
      presented with groups I to III (15 eyes) and group V (one eye) disease, whereas
      enucleation could be avoided in only two (40%) of five. CONCLUSION: CT combined
      with intensive LT is effective in patients with groups I to III Rbl, permitting
      the avoidance of EBR in the majority of these young children and, thus, reducing
      the risk of long-term sequelae. This is in contrast with the disappointing
      results for patients with groups IV and V Rbl, in whom EBR and/or enucleation was
      needed.

PMID- 10920137
TI  - p27(kip1) protein expression correlates with survival in myxoid and round-cell
      liposarcoma.
AB  - PURPOSE: The p27(kip1) protein (p27) is a cyclin-dependent kinase inhibitor that
      has been shown to be an independent prognostic factor in a variety of human
      neoplasms. Low expression of p27 tends to occur in more aggressive neoplasms. The
      role of p27 as an independent prognostic factor in the spectrum of myxoid and
      round-cell liposarcomas has not been examined. MATERIALS AND METHODS: Forty-seven
      cases of myxoid and round-cell liposarcomas were examined. Clinicopathologic
      features and immunohistochemical expression of p27 and Ki-67 antigen were studied
      in all cases. Survival analysis was performed using the log-rank test and the Cox
      multivariate regression model. RESULTS: The male:female ratio was 1. 4:1, and the
      mean age at diagnosis was 45 years. The tumors were located in the lower
      extremities (94%) and retroperitoneum (6%). The median tumor size was 13.5 cm.
      The median follow-up was 6.3 years, and the overall 5- and 10-year survival rates
      were 76% and 67%, respectively. Low expression of p27 was identified in 34 cases
      (72%) and correlated with decreased metastasis-free (P =.026) and overall
      survival (P =.008). In a multivariate analysis, only round-cell differentiation
      and low expression of p27 independently predicted decreased metastasis-free and
      overall survival. CONCLUSION: p27 expression predicts the clinical behavior of
      myxoid and round-cell liposarcomas, even in neoplasms with few or no round-cell
      differentiation.

PMID- 10920138
TI  - Multicenter phase II study to evaluate a 28-day regimen of oral fluorouracil plus
      eniluracil in the treatment of patients with previously untreated metastatic
      colorectal cancer.
AB  - PURPOSE: To determine the efficacy of fluorouracil (5-FU) plus eniluracil when
      administered to patients with previously untreated metastatic colorectal cancer.
      PATIENTS AND METHODS: In this single-arm phase II study, patients with previously
      untreated metastatic colorectal cancer received oral eniluracil plus 5-FU (10:1
      dose ratio), at 5-FU doses of 1.00 mg/m(2) or 1.15 mg/m(2) twice daily (every 12
      hours) for 28 consecutive days repeated every 5 weeks (one cycle). Treatment
      continued until there was documented disease progression or unacceptable
      toxicity. RESULTS: Thirty and 25 patients were enrolled at a starting dose of
      1.00 mg/m(2) and 1.15 mg/m(2), respectively. Fourteen (25%) of 55 patients (95%
      confidence interval, 15% to 39%) had a partial response, and 20 patients (36%)
      had stable disease. The median durations of the partial responses and stable
      disease were 23.9 weeks (range, 12.3 to 52.1+ weeks) and 24.1 weeks (range, 17.1
      to 55.6+ weeks), respectively. The median durations of progression-free and
      overall survival were 22.6 weeks (range, 21.0 to 29.0 weeks) and 59 weeks (range,
      4 to 84+ weeks), respectively. The response rate in the 1.15 mg/m(2)-dose group
      was similar to the 1.00 mg/m(2)-dose group (28% v 23%, respectively). Severe
      (grade 3/4) nonhematologic treatment-related toxicity included diarrhea (nine
      patients), nausea/vomiting (one patient each), mucositis (two patients), and
      anorexia (one patient). Severe hematologic toxicities were rare. At the 1.15
      mg/m(2)-dose level, two patients exhibited grade 3 granulocytopenia, and two
      patients had grade 3 anemia. CONCLUSION: The response rate with oral 5-FU plus
      eniluracil is comparable with that observed with infusional 5-FU or bolus 5-FU
      and leucovorin. The toxicity profile of this oral regimen is acceptable for use
      in an outpatient home-based setting.

PMID- 10920139
TI  - Communication between primary care physicians and radiation oncologists regarding
      patients with cancer treated with palliative radiotherapy.
AB  - PURPOSE: The purpose of this study was to assess the satisfaction and information
      needs of primary care physicians (PCPs) regarding communication with radiation
      oncologists (ROs), with respect to patients who receive palliative radiotherapy
      (RT). A selected objective was to evaluate the agreement between PCPs'
      expectations and the content of the RO letter sent after completion of RT. PCPs'
      knowledge of the role of palliative RT and their awareness of available patient
      support services were also determined. METHODS: The PCPs of patients discharged
      from the Cross Cancer Institute after receiving palliative RT were surveyed using
      a mail-out questionnaire. Questions regarding communication, RT knowledge, and
      awareness of support services were asked. The corresponding RO letter was
      reviewed. RESULTS: A total of 148 PCPs were identified and were mailed
      questionnaires, with 114 (77%) responding. Overall, 80% (87 of 109) of PCPs found
      the RO letter to be useful in patient management. However, there was poor (< 53%)
      agreement between PCPs' expectations and the actual content of the RO letter.
      Knowledge of the indications and effectiveness of palliative RT was limited, with
      PCPs obtaining a median score of 4 of a possible 8. Only 27% (31 of 114) of PCPs
      were aware of all five of the patient support services listed. CONCLUSION:
      Results show that although the majority of PCPs found the RO letter useful, they
      believed that the letter lacked important information while containing
      unnecessary details. Communication between PCPs and ROs needs improvement,
      especially considering that PCPs seem to have limited knowledge of palliative RT.

PMID- 10920140
TI  - Primary cutaneous T-cell lymphoma: review and current concepts.
AB  - PURPOSE: Primary cutaneous T-cell lymphomas (CTCLs) encompass a wide variety of
      lymphomas that are characterized by the localization of the malignant lymphocytes
      to the skin at presentation. Advances in molecular biologic techniques, including
      immunophenotyping and gene rearrangement studies to determine clonality, have led
      to more frequent diagnosis of CTCL as well as more consistent subclassification
      of these entities. However, there continues to be confusion in the
      classification, prognosis, and management of patients with CTCL. The purpose of
      this review is to present a summary of the diagnosis, prognosis, and treatment of
      CTCL, with specific emphasis on mycosis fungoides (MF) and Sezary syndrome (SS).
      We also present a detailed discussion of the entities that make up the
      differential diagnosis of CTCL. DESIGN: We reviewed the medical literature on
      CTCL and other diseases that make up the differential diagnosis of CTCL. RESULTS
      AND CONCLUSION: MF and SS are the most common forms of CTCL. The etiology of this
      disease is still unknown. Patients may go for months to years with skin
      abnormalities before being diagnosed. MF/SS is an indolent disease and patients
      with T1 disease have a normal life expectancy. Patients who undergo
      transformation to large-cell lymphoma (8% to 23% of patients) have a poor
      prognosis, with mean survival ranging from 2 to 19 months. Treatment for MF/SS
      continues to be palliative. There are many new therapies that are currently being
      investigated in clinical trials, and the DAB(389)IL-2 fusion protein was recently
      approved for the treatment of refractory MF/SS.

PMID- 10920141
TI  - Meningeal carcinomatosis in lung cancer. Case 1. Carcinomatous leptomeningeal
      metastases.

PMID- 10920142
TI  - Meningeal carcinomatosis in lung cancer. Case 2. Carcinomatous meningitis.

PMID- 10920143
TI  - On appetite and its loss.

PMID- 10920144
TI  - Bezwoda: evidence of fabrication in original article.

PMID- 10920145
TI  - Head growth in infants with hypoxic-ischemic encephalopathy: correlation with
      neonatal magnetic resonance imaging.
AB  - OBJECTIVES: The aims of the study were to establish the relationship between head
      growth in the first year of life with the pattern on injury on neonatal magnetic
      resonance imaging (MRI) in infants with hypoxic-ischemic encephalopathy (HIE) and
      to relate these to the neurodevelopmental outcome. METHODS: Fifty-two term
      infants who presented at birth with a neonatal encephalopathy consistent with HIE
      and who had neonatal brain MRI were entered into the study. Head circumference
      charts were evaluated retrospectively and the head growth over the first year of
      life compared with the pattern of brain lesions on MRI and with the
      neurodevelopmental outcome at 1 year of age. Suboptimal head growth was
      classified as a drop of >2 standard deviations across the percentiles with or
      without the development of microcephaly, which was classified as a head
      circumference below the third percentile. RESULTS: There was no statistical
      difference between the neonatal head circumferences of the infants presenting
      with HIE and control infants. At 12 months, microcephaly was present in 48% of
      the infants with HIE, compared with 3% of the controls. Suboptimal head growth
      was documented in 53% of the infants with HIE, compared with 3% of the controls.
      Suboptimal head growth was significantly associated with the pattern of brain
      lesions, in particular to involvement of severe white matter and to severe basal
      ganglia and thalamic lesions. Suboptimal head growth predicted abnormal
      neurodevelopmental outcome with a sensitivity of 79% and a specificity of 78%,
      compared with the presence of microcephaly at 1 year of age, which had a
      sensitivity of only 65% and a specificity of 73%. The exceptions were explained
      by infants with only moderate white matter abnormalities who had suboptimal head
      growth but normal outcome at 1 year of age and by infants with moderate basal
      ganglia and thalamic lesions only who had normal head growth but significant
      motor abnormality.

PMID- 10920146
TI  - The influence of intrapartum antibiotics on the clinical spectrum of early-onset
      group B streptococcal infection in term infants.
AB  - OBJECTIVE: The use of intrapartum antibiotics to prevent early-onset group B
      streptococcal (EOGBS) infection has left pediatricians in a quandary about the
      appropriate evaluation and treatment of infants at risk for this infection. The
      aim of this study was to determine whether intrapartum antibiotic prophylaxis
      changed the constellation and timing of onset of clinical signs of group B
      streptococcal (GBS) infection in term infants. METHODOLOGY: We conducted a
      retrospective chart review of infants who had EOGBS infection and were born in
      Southern California Kaiser Permanente Hospitals from 1988 through 1996. Objective
      criteria were used to ascertain maternal risk of infection, intrapartum
      antibiotic prophylaxis, and onset of clinical signs of infection. RESULTS: Three
      hundred nineteen infants with EOGBS sepsis, bacteremia, or clinically suspected
      infection were identified from a population of 277 912 live births. Of the 172
      term infants with culture-positive infection who had clinical signs of infection,
      95% exhibited them in the first 24 hours of life. All of the infants exposed to
      intrapartum antibiotics became ill within the first 24 hours of life.
      CONCLUSIONS: Exposure to antibiotics during labor did not change the clinical
      spectrum of disease or the onset of clinical signs of infection within 24 hours
      of birth for term infants with EOGBS infection. A 48-hour stay is not required to
      monitor asymptomatic term infants exposed to intrapartum antibiotics for onset of
      GBS infection.

PMID- 10920147
TI  - Outpatient pediatric blood cultures: time to positivity.
AB  - OBJECTIVE: Using a continuously monitoring blood culture system, we determined
      the time to positivity of blood cultures performed on immunocompetent infants and
      children who were not receiving antibiotics at the time of culture. STUDY DESIGN:
      This study was conducted prospectively using blood cultures taken in the
      emergency department and outpatient clinics of an urban pediatric teaching
      hospital from February 1, 1993, through December 31, 1996. Cultures were excluded
      if obtained from patients receiving antibiotics, patients with a central line,
      patients with prosthetic devices, or those being followed by the oncology
      division. Our measures included: 1) recording the time to positive culture
      obtained by using a continuously monitoring blood culture instrument, 2) patient
      information derived from the hospital computer system concerning antibiotic use
      and the presence of indwelling central venous catheters and prosthetic devices,
      and 3) a chart review of 10% of patients from whom positive cultures were
      obtained. RESULTS: During the 47-month study period, 10 200 single bottle blood
      cultures were obtained, 711 (6.97%) of which became positive. Patients ranged in
      age from <1 week to 24 years (mean: 2.00 years). Two hundred fifty-eight cultures
      (36.3%) contained only pathogens, 370 (52%) contained only skin contaminants, and
      83 (11.7%) contained a mixture of contaminant and pathogen. Of the 258 cultures
      containing only pathogens, 14% were positive by 12 hours, 87% by 24 hours, 92% by
      36 hours, 95% by 48 hours, 98% by 60 hours, and 99.7% by 72 hours. Ninety-five
      percent of critical pediatric pathogens including Streptococcus pneumoniae,
      Salmonella and other Enterobacteriaceae, Neisseria meningitidis, and groups A and
      B streptococci were detected in <24 hours. CONCLUSION: Because 87% of all
      cultures containing pathogens were detected within the first 24 hours of
      incubation, this study can assist emergency department, clinic, and primary care
      clinicians when making critical decisions concerning patients on whom blood
      cultures were obtained. Data on time to positivity of blood cultures can be used
      in conjunction with clinical status to support clinicians in making patient
      management decisions. Use of short stay (</=24 hours) or extended care units
      requiring less patient supervision may be easier to justify when a continuously
      monitoring blood culture instrument is used in the microbiology
      laboratory.bacteremia, sepsis.

PMID- 10920148
TI  - Neonatal sepsis workups in infants >/=2000 grams at birth: A population-based
      study.
AB  - BACKGROUND: Few data are available on the outcome of neonatal sepsis evaluations
      in an era when intrapartum antibiotic therapy is common. METHODS: We identified
      all newborns weighing >/=2000 g at birth who were ever evaluated for suspected
      bacterial infection at 6 Kaiser Permanente hospitals between October 1995 and
      November 1996, reviewed their records and laboratory data, and tracked them to 1
      week after discharge. We analyzed the relationship between key predictors and the
      presence of neonatal bacterial infection. RESULTS: Among 18 299 newborns >/=2000
      g without major congenital anomalies, 2785 (15.2%) were evaluated for sepsis with
      a complete blood count and/or blood culture. A total of 62 (2.2%) met criteria
      for proven, probable, or possible bacterial infection: 22 (.8%) had positive
      cultures and 40 (1.4%) had clinical evidence of bacterial infection. We tracked
      all but 10 infants (.4%) to 7 days postdischarge. There were 67
      rehospitalizations (2.4%; 2 for group B streptococcus bacteremia). Among 1568
      infants who did not receive intrapartum antibiotics, initial asymptomatic status
      was associated with decreased risk of infection (adjusted odds ratio [AOR]:.26;
      95% confidence interval [CI]:.11-.63), while chorioamnionitis (AOR: 2. 40; 95%
      CI: 1.15-5.00), low absolute neutrophil count (AOR: 2.84; 95% CI: 1.50-5.38), and
      meconium-stained amniotic fluid (AOR: 2.23; 95% CI: 1.18-4.21) were associated
      with increased risk. Results were similar among 1217 infants who were treated,
      except that maternal chorioamnionitis was not significantly associated with
      neonatal infection. CONCLUSIONS: The risk of bacterial infection in asymptomatic
      newborns is low. Evidence-based observation and treatment protocols could be
      defined based on a limited set of predictors: maternal fever, chorioamnionitis,
      initial neonatal examination, and absolute neutrophil count. Many missed
      opportunities for treating mothers and infants exist.

PMID- 10920149
TI  - Parental preferences for primary and specialty care collaboration in the
      management of teenagers with congenital heart disease.
AB  - OBJECTIVES: We examined parental preferences for locus of service delivery for
      their teenager's congenital heart disease (CHD) and the influence of disease
      severity, sociodemographic factors, and insurance on these preferences. METHODS:
      A consecutive sample of parents of teenagers followed in a pediatric cardiology
      clinic completed a mailed questionnaire. Disease severity was classified as low
      (</=1 cardiovascular procedure), moderate (>1 cardiovascular procedure), and high
      (cyanosis or single ventricle physiology). RESULTS: Eighty-six of 148 parents
      responded (58%): 40, low severity; 36, moderate severity; and 10, high severity
      of illness. Parents preferred using primary care providers (PCPs) as a point of
      first contact for all 11 of 11 general health concerns and 5 of 7 potential
      cardiovascular-related concerns: chest pain (52%), syncope (73%), seeming
      seriously ill (79%), sports physical examination (79%), and endocarditis
      prophylactic antibiotics (94%). Increasing disease severity was significantly
      associated with preferring cardiologists for 6 of 7 cardiovascular-related
      concerns. Overall, 58% of parents viewed their care as a PCP-cardiologist
      comanagement model versus a cardiologist-dominated model. Lower family income
      (odds ratio [OR]: 1.5; confidence interval [CI]: 1.0-2.2) and severity of illness
      (OR: 2.1; CI: 1.0-4.4) were associated with a comanagement model of health care
      versus a cardiologist-dominated model. CONCLUSIONS: This study suggests that the
      majority of parents of teenagers with CHD prefer to use their teenager's PCP for
      all routine health care needs and many cardiovascular health needs. Severity of
      illness and family income are positively associated with greater preference for
      cardiologist care.

PMID- 10920150
TI  - Pain experience of children with headache and their families: A controlled study.
AB  - OBJECTIVE: This study reports the pain sensitivity of children with headache and
      their family members, as well as the prevalence of recurring aches, psychosocial
      life, and family environment of children with headache at preschool age. DESIGN:
      A representative population-based sample of 1443 families expecting their first
      child were followed over 7 years. A screening questionnaire relating to the
      child's headache was sent to parents of a representative sample of 1132 6-year
      old children. Of 144 children suffering from headache, 106 (76%) were examined
      and interviewed clinically. Ninety-six children with primary headache (58
      migraine and 38 tension-type headache children) and matched controls (n = 96)
      were included in further examinations. RESULTS: Children with headache were more
      often extremely sensitive to pain according to their parents, were more excited
      about physical examinations, cried more often during blood sampling or
      vaccination, avoided play or games more often because they were afraid of hurting
      themselves, and had recurring abdominal and growing pains more often than did
      control children. The fathers of children with headache were more often extremely
      sensitive to pain. Children with headache reacted with somatic symptoms, usually
      with pain and functional intestinal disorders in stress situations, felt more
      tired, and had more ideations of death during the previous month. They had also
      had more problems in day care and fewer hobbies such as scout or club meetings
      than did control children. More mothers of tension-type headache children than
      those of migraine children reported that they were considerably sensitive to
      pain. Tension-type headache children also had a poorer family environment; the
      family atmosphere was more often unhappy and the relationship between the parents
      was more often distant than in the families of children with migraines.
      CONCLUSIONS: In addition to somatic factors, it is important to consider the
      child's pain sensitivity, reaction to various stress situations, and family
      functioning when studying childhood headache. The child's coping mechanisms can
      be supported by information given by the parents. School entry can be considered
      a suitable period for careful investigation into possible occurrence of headache
      and also for giving information about headache and its management.

PMID- 10920151
TI  - Perineal group A streptococcal disease in a pediatric practice.
AB  - OBJECTIVE: This study was designed to document the frequency and define the
      clinical, epidemiologic, and microbiologic characteristics of perineal disease
      caused by group A beta-hemolytic streptococci (GAS) in a pediatric practice in
      which increased numbers of cases had been observed. METHODS: Clinical,
      epidemiologic, and microbiologic data were collected on all culture-confirmed
      cases of perineal GAS disease during the calendar year 1997. GAS isolates from
      clinical cases and a comparison group of children with GAS pharyngitis were
      analyzed by T typing, emm gene analysis, and pulsed-field gel electrophoresis
      (PFGE). RESULTS: Twenty-three cases of GAS perineal disease were diagnosed during
      4530 office visits in 1997. Thirteen cases had perianal disease, 8 had
      vulvovaginal infection, and 2 were infected at both sites. No cases of penile
      disease were identified. Infections peaked in late winter and early spring and
      affected children with an average age of 5 years with a range of perineal,
      gastrointestinal, and genitourinary symptoms. Analysis of T and emm types showed
      the majority (82%) of perineal isolates to be T 28 emm 28, showing 2 closely
      related PFGE patterns. In contrast, the pharyngeal isolates were distributed
      among 6 different T and emm types. CONCLUSION: Perineal infection caused by GAS
      may be a relatively common diagnosis in a pediatric or family practice setting.
      There may be specific GAS types that have a tropism for perineal tissues but the
      mechanism of infection is yet to be established.

PMID- 10920152
TI  - High-versus low-threshold surfactant retreatment for neonatal respiratory
      distress syndrome.
AB  - Surfactant therapy has become an effective standard therapy for infants with
      respiratory distress syndrome (RDS). The first dose may be given either as
      prophylaxis immediately after delivery, or as rescue after an infant has
      developed RDS. Second and subsequent doses are currently recommended by the
      manufacturers to be administered at minimal levels of respiratory support.
      PURPOSE: This study compared the relative efficacy of administering second and
      subsequent doses of Infasurf surfactant at a low threshold (FIO(2) >30%, still
      requiring endotracheal intubation) versus a high threshold (FIO(2) >40%, mean
      airway pressure >7 cm H(2)O) of respiratory support. METHODS: A total of 2484
      neonates received a first dose of surfactant; 1267 reached conventional
      retreatment criteria and were randomized to be retreated according to low- or
      high-threshold criteria. They were then retreated at a minimum of 6-hour
      intervals each time they reached their assigned threshold until receiving a
      maximum of 4 total doses. Subjects were stratified by whether they received their
      first dose by prophylaxis or rescue and by whether their lung disease was
      considered complicated (evidence of perinatal compromise or sepsis) or
      uncomplicated. RESULTS: Among the patients randomized, 33% of prophylaxis and 23%
      of rescue subjects met criteria for the complicated stratum. Although infants
      allocated to the high-threshold strategy were receiving slightly more oxygen at
      72 hours, there was no difference in the number receiving mechanical ventilation
      at 72 hours or in the secondary respiratory outcomes (requirement for
      supplemental oxygen or mechanical ventilation at 28 days, supplemental oxygen at
      36 weeks' postconceptional age, inspired oxygen concentration >60% at any time).
      However, there was a significantly higher mortality for infants with complicated
      RDS who had received retreatment according to the high-threshold strategy.
      CONCLUSIONS: We conclude that equal efficacy can be realized by delaying
      surfactant retreatment of infants with uncomplicated RDS until they have reached
      a higher level of respiratory support than is the current standard. We speculate
      that this would result in a substantial cost-saving from less utilization of
      drug. Conversely, we believe that infants with complicated RDS should continue to
      be treated by the low-threshold retreatment strategy, which is currently
      recommended by the manufacturers of the commercially available surfactants.

PMID- 10920153
TI  - Volume-outcome relationships in pediatric intensive care units.
AB  - CONTEXT: Pediatric intensive care units (PICUs) have expanded nationally, yet few
      studies have examined the potential impact of regionalization and no study has
      demonstrated whether a relationship between patient volume and outcome exists in
      these units. Documentation of an inverse relationship between volume and outcome
      has important implications for regionalization of care. OBJECTIVES: This study
      examines relationships between the volume of patients and other unit
      characteristics on patient outcomes in PICUs. Specifically, we investigate
      whether an increase in patient volume improves mortality risk and reduces length
      of stay. DESIGN AND SETTING: A prospective multicenter cohort design was used
      with 16 PICUs. All of the units participated in the Pediatric Critical Care Study
      Group. Participants. Data were collected on 11 106 consecutive admissions to the
      16 units over a 12-month period beginning in January 1993. MAIN OUTCOME MEASURES:
      Risk-adjusted mortality and length of stay were examined in multivariate
      analyses. The multivariate models used the Pediatric Risk of Mortality score and
      other clinical measures as independent variables to risk-adjust for illness
      severity and case-mix differences. RESULTS: The average patient volume across the
      16 PICUs was 863 with a standard deviation of 341. We found significant effects
      of patient volume on both risk-adjusted mortality and patient length of stay. A
      100-patient increase in PICU volume decreased risk-adjusted mortality (adjusted
      odds ratio:.95; 95% confidence interval:.91-.99), and reduced length of stay
      (incident rate ratio:.98; 95% confidence interval:.975-.985). Other PICU
      characteristics, such as fellowship training program, university hospital
      affiliation, number of PICU beds, and children's hospital affiliation, had no
      effect on risk-adjusted mortality or patient length of stay. CONCLUSIONS: The
      volume of patients in PICUs is inversely related to risk-adjusted mortality and
      patient length of stay. A further understanding of this relationship is needed to
      develop effective regionalization and referral policies for critically ill
      children.

PMID- 10920154
TI  - Sudden infant death syndrome in child care settings.
AB  - BACKGROUND: The incidence of sudden infant death syndrome (SIDS) in the United
      States has decreased with decreased prone sleeping. Extrapolating from Census
      Bureau data, approximately 7% of SIDS should occur in organized child care
      settings (ie, child care centers or family child care homes). However, 2 states
      have reported higher rates of SIDS in child care. OBJECTIVES: To determine the
      percentage of SIDS deaths occurring in child care settings, and to ascertain
      associated factors. DESIGN: A retrospective study of SIDS deaths from January
      1995 through June 1997 was conducted. Data were abstracted from SIDS databases in
      11 states. Characteristics of SIDS cases occurring in child care settings,
      including sleep position, were compared with those occurring in the care of
      parents. Univariate and multiple logistic regression analyses were performed.
      RESULTS: A total of 1916 SIDS cases were analyzed for this study. Of these
      deaths, 20.4% occurred in child care settings. Compared with deaths in the care
      of parents, those occurring in child care settings were more likely to occur on
      weekdays between 8:00 AM and 4:00 PM; infants were older; not black; and their
      mothers were more educated. Infants in child care were more likely to be found
      prone in univariate analysis, but the association was not significant in multiple
      logistic regression analysis. However, in multiple regression analysis, infants
      in child care were more likely to be last placed prone or found prone, when the
      usual sleep position was side or supine. CONCLUSION: A large proportion (20.4%)
      of SIDS cases occur in child care settings. Factors associated with SIDS in child
      care settings include older age, race, and highly educated parents. Previous
      studies have reported that unaccustomed prone sleeping puts infants at high risk
      for SIDS; this characteristic was found to be associated with SIDS in child care
      and may partly explain the high proportion of SIDS cases in child care settings.
      Parents must discuss sleep position with any caretakers of their infants. In
      addition, further efforts to educate child care providers about the importance of
      supine sleep for infants must be ongoing.

PMID- 10920155
TI  - Can falls on stairs result in small intestine perforations?
AB  - OBJECTIVE: Abusive parents often report that a fall on stairs resulted in their
      children's injuries. This review explores whether there is any evidence in the
      medical literature that a fall on stairs could be a plausible explanation for a
      small intestine perforation. METHODOLOGY: The English-language medical literature
      was searched by Medline, for a 29-year period (1970-1998), for reports of the
      types of injuries sustained in falls on stairs and for reports of the types of
      blunt abdominal trauma that result in small intestine perforations. Articles that
      exclusively focused on infant walker injuries or the elderly were excluded.
      Duodenal, jejunal, and ileal perforations were included, whereas intestinal
      hematomas and undescribed intestinal injuries were excluded. All types of
      injuries to the stomach, colon, and rectum were excluded. RESULTS: Falls on
      stairs were not reported to be a cause for any of the 312 cases of small
      intestine perforations reviewed. There were no reports of any intraabdominal
      injuries, including small intestine perforations, in any of the 677 cases of
      falls on stairs reviewed. Falls on stairs rarely resulted in any type of truncal
      injury. CONCLUSIONS: Although falls on stairs have been reported to be the most
      common cause of injury in childhood, no evidence was found to support the
      contention that an unobstructed fall on stairs could be consistent with
      perforation of the small intestine.

PMID- 10920156
TI  - Impact of race and gestational age on red blood cell indices in very low birth
      weight infants.
AB  - BACKGROUND: Normative data for hematologic values in the very low birth weight
      infants are limited and inconsistent, with the reported mean hematocrit (HCT) in
      these infants ranging from 43.5% to 60%. No data are available on the effect of
      race. OBJECTIVES: To establish normative data for hemoglobin (Hb) and HCT by
      arterial sampling obtained during the first 3 hours after birth in black and
      white premature infants </=31 weeks of gestation. METHODS: Retrospective chart
      review of all infants </= 31 weeks of gestation born between June 1994 and
      October 1998. INCLUSION CRITERIA: infant </=31 weeks of gestation who had an
      arterial blood sample obtained in the first 3 hours after birth. EXCLUSION
      CRITERIA: infants were excluded if they had any medical condition that may affect
      the red blood cell indices (eg, twin-to-twin transfusion or fetomaternal
      hemorrhage). RESULTS: Of 428 infants, 188 who met both inclusion and exclusion
      criteria were classified into 3 gestational age groups: group 1 = 23 to 25 weeks
      of gestation (n = 40); group 2 = 26 to 28 weeks (n = 60); and group 3 = 29 to 31
      weeks (n = 88). There were statistically significant differences between groups 1
      and 3 in HCT, Hb, mean corpuscular Hb (MCH), and mean corpuscular volume (MCV).
      No differences in HCT and Hb values were noted in relation to sex, mode of
      delivery, multiple gestation, antenatal steroids, or maternal smoking. In group
      3, the mean Hb, HCT, and MCV values were higher in white infants than in black
      infants (16.7 +/- 1.6 g/dL vs 15.4 +/- 1. 7 g/dL; 50.0 +/- 5.0 vs 45.5 +/- 4.6;
      and 112 +/- 5 fL vs 107 +/- 8 fL, respectively). CONCLUSIONS: Hb, HCT, and MCH
      values are described for premature infants </=31 weeks of gestation born in North
      America. Hb and HCT increased, whereas MCV decreased with gestational age. Hb,
      HCT, and MCV values are statistically higher in white infants than in black
      infants.

PMID- 10920157
TI  - High-dose albuterol by metered-dose inhaler plus a spacer device versus
      nebulization in preschool children with recurrent wheezing: A double-blind,
      randomized equivalence trial.
AB  - Inhaled albuterol is the most frequently used bronchodilator for acute wheezing,
      and nebulization is the standard mode of delivery in hospital setting. However,
      recent guidelines consider spacer devices as an easier to use, and cost-saving
      alternative and recommend the high-dose metered-dose inhaler bronchodilator.
      OBJECTIVE: To demonstrate clinical equivalence between a spacer device and a
      nebulizer for albuterol administration. DESIGN: Randomized, double-blind,
      parallel group equivalence trial. SETTING: Pediatric emergency wards at 2
      tertiary teaching hospitals. PATIENTS: Sixty-four 12- to 60-month-old children
      with acute recurrent wheezing (32 per group). INTERVENTIONS: Albuterol was
      administered through the spacer device (50 microg/kg) or through the nebulizer
      (150 microg/kg) and repeated 3 times at 20-minute intervals. Parents completed a
      questionnaire. OUTCOME MEASURES: Pulmonary index, hospitalization, ease of use,
      acceptability, and pulse oximetry saturation. RESULTS: The 90% confidence
      interval of the difference between treatment groups for the median absolute
      changes in pulmonary index values between T0 and T60 was [-1; +1] and was
      included in the equivalence interval [-1.5; +1.5]. Clinical improvement increased
      with time. Less than 10% of the children (3 in each group) required
      hospitalization (2 in each group attributable to treatment failure). Parents
      considered administration of albuterol using the spacer device easier (94%) and
      better accepted by their children (62%). CONCLUSIONS: The efficacy of albuterol
      administered using the spacer device was equivalent to that of the nebulizer.
      Given its high tolerance, repeated 50-microg/kg doses of albuterol administered
      through the spacer device should be considered in hospital emergency departments
      as first-line therapy for wheezing.

PMID- 10920158
TI  - Brainstem maturation in premature infants as a function of enteral feeding type.
AB  - OBJECTIVE: To determine whether brainstem maturation as measured by brainstem
      auditory-evoked responses (BAERs) in preterm infants is a function of dietary
      intake. STUDY DESIGN: We obtained serial BAERs on infants 28 to 32 weeks'
      gestation at birth, cared for in the neonatal intensive care unit of a regional
      referral center in Upstate New York. Waveforms were analyzed for replicability
      and for the presence of waves III and V. Absolute and interwave latencies were
      measured. Baseline and follow-up BAER measurements were compared, and the rates
      of change were calculated. Patient charts were reviewed for type of enteral
      feeding during the interval between BAERs. Student's t test was used to analyze
      continuous variables and chi(2) analysis was used to analyze categorical
      variables. RESULTS: Data from 37 study infants (17 fed breast milk and 20 fed
      commercial premature formula) revealed that there was no difference in absolute
      latencies of waves III and V at baseline; however, the rates of decrease of
      absolute latencies over the study interval were significantly greater in infants
      receiving human milk. CONCLUSIONS: Infants fed breast milk have faster brainstem
      maturation, compared with infants fed formula, based on the rate of maturation of
      BAERs. This effect may be attributable to the constituent composition of breast
      milk, compared with synthetic formulas.

PMID- 10920159
TI  - Pediatric residency education.
AB  - OBJECTIVE: On February 1, 1997, new pediatric Residency Review Committee
      guidelines became effective. Eighteen months later, pediatric residency program
      directors were queried regarding the implementation of these guidelines. Because
      both the challenge to implement these guidelines and the opportunities to shape
      pediatric graduate medical education rest with the program directors, obtaining
      the feedback and suggestions from this group is seen as the keystone of future
      planning endeavors. METHODS: A 20-question multiple-choice/opened-ended
      questionnaire was sent to the 201 members of the Association of Pediatric Program
      Directors in 2 mailings in August and September 1998. RESULTS: A final response
      rate of 70% was achieved. Very few program directors reported difficulties in
      instituting the new residency review committee requirements. The exceptions to
      this pattern were those requirements pertaining to limitations on time spent in
      intensive care experience and in the neonatal intensive care unit, wherein 34% of
      the respondents identified barriers. Although the majority of respondents
      regarded these requirements as very good or sufficient, some program directors
      expressed concern regarding insufficient amounts of time available for
      preparation in intensive care (18%), neonatal intensive care unit (22%),
      behavioral/developmental pediatrics (16%), and in adolescent medicine (13%). In
      general, programs have been more successful in defining new competencies than in
      developing curricula to teach them. The majority of respondents also indicated
      that their residents' exposure was excellent or satisfactory in all 6 of the
      following practice settings: private office-based practice for continuity clinic,
      private office-based practice for outpatient rotation, predominately managed care
      practice, community clinics for continuity clinic, community clinics for
      outpatient rotation, and hospital-based practice for continuity clinic. They also
      indicated that they had no serious concerns about the types of career development
      assistance offered to residents and the types of follow-up tracking of residents.
      CONCLUSION: The findings from this survey have reaffirmed the merit of the
      current system of pediatric residency education. They have also revealed the
      commitment of program directors to address the complex issues generated by the
      evolution of health care delivery, and thereby contribute to the optimal
      provision of pediatric health care now and in the future.

PMID- 10920160
TI  - Pediatric emergencies in the office, hospital, and community: organizing systems
      of care.

PMID- 10920161
TI  - Hypnosis, Theodore Roosevelt, and the patient with cystic fibrosis.

PMID- 10920162
TI  - Neonatal alloimmune neutropenia in premature monozygous twins.
AB  - Alloimmune neonatal neutropenia (ANN) is an uncommon but potentially life
      threatening disorder of the neonate and young infant. Hematologically, the
      mother's peripheral neutrophil count is normal. However, the passive transfer of
      maternal immunoglobulin G neutrophil-specific antibodies and the subsequent
      sensitization of fetal neutrophils can result in severe neutropenia in the
      neonate. Generally, ANN is a self-limiting condition, but with severe bacterial
      infection, mortality can be high. We present the clinical features of monozygous
      twins delivered at 33 weeks' postconception with this condition. This case report
      is unique in that it occurred in twins born prematurely and was attributable to
      antibodies against 2 neutrophil-specific antigens, NA1 and NB1. A brief review of
      the diagnosis, management, and treatment of ANN is presented.

PMID- 10920163
TI  - American Academy of Pediatrics. Committee on School Health. Corporal punishment
      in schools.
AB  - The American Academy of Pediatrics recommends that corporal punishment in schools
      be abolished in all states by law and that alternative forms of student behavior
      management be used.

PMID- 10920164
TI  - American Academy of Pediatrics. Committee on Fetus and Newborn. Use of inhaled
      nitric oxide.
AB  - Approval of inhaled nitric oxide by the US Food and Drug Administration for
      hypoxic respiratory failure of the term and near-term newborn provides an
      important new therapy for this serious condition. This statement addresses the
      conditions under which inhaled nitric oxide should be administered to the neonate
      with hypoxic respiratory failure.

PMID- 10920165
TI  - American Academy of Pediatrics. Committee on Nutrition. Hypoallergenic infant
      formulas.
AB  - The American Academy of Pediatrics is committed to breastfeeding as the ideal
      source of nutrition for infants. For those infants who are formula-fed, either as
      a supplement to breastfeeding or exclusively during their infancy, it is common
      practice for pediatricians to change the formula when symptoms of intolerance
      occur. Decisions about when the formula should be changed and which formula
      should be used vary significantly, however, among pediatric practitioners. This
      statement clarifies some of these issues as they relate to protein
      hypersensitivity (protein allergy), one of the causes of adverse reactions to
      feeding during infancy.

PMID- 10920166
TI  - American Academy of Pediatrics. Committee on Hospital Care. Precertification
      process.
AB  - Precertification is a process still used by health insurance companies to control
      health care costs. Although we believe precertification is unnecessary and not
      cost-effective, in those instances where precertification is still being
      utilized, we suggest that the following procedures be adopted. This statement
      suggests guidelines that should help achieve this goal while allowing optimal
      access to care for children.

PMID- 10920167
TI  - American Academy of Pediatrics. Committee on Bioethics and Committee on Hospital
      Care. Palliative care for children.
AB  - This statement presents an integrated model for providing palliative care for
      children living with a life-threatening or terminal condition. Advice on the
      development of a palliative care plan and on working with parents and children is
      also provided. Barriers to the provision of effective pediatric palliative care
      and potential solutions are identified. The American Academy of Pediatrics
      recommends the development and broad availability of pediatric palliative care
      services based on child-specific guidelines and standards. Such services will
      require widely distributed and effective palliative care education of pediatric
      health care professionals. The Academy offers guidance on responding to requests
      for hastening death, but does not support the practice of physician-assisted
      suicide or euthanasia for children.

PMID- 10920168
TI  - American Academy of Pediatrics. Committee on Substance Abuse and Committee on
      Children With Disabilities. Fetal alcohol syndrome and alcohol-related
      neurodevelopmental disorders.
AB  - Prenatal exposure to alcohol is one of the leading preventable causes of birth
      defects, mental retardation, and neurodevelopmental disorders. In 1973, a cluster
      of birth defects resulting from prenatal alcohol exposure was recognized as a
      clinical entity called fetal alcohol syndrome. More recently, alcohol exposure in
      utero has been linked to a variety of other neurodevelopmental problems, and the
      terms alcohol-related neurodevelopmental disorder and alcohol-related birth
      defects have been proposed to identify infants so affected. This statement is an
      update of a previous statement by the American Academy of Pediatrics and reflects
      the current thinking about alcohol exposure in utero and the revised nosology.

PMID- 10920169
TI  - American Academy of Pediatrics. Committee on Infectious Diseases. Policy
      statement: recommendations for the prevention of pneumococcal infections,
      including the use of pneumococcal conjugate vaccine (Prevnar), pneumococcal
      polysaccharide vaccine, and antibiotic prophylaxis.
AB  - Heptavalent pneumococcal conjugate vaccine (PCV7) is recommended for universal
      use in children 23 months and younger, to be given concurrently with other
      recommended childhood vaccines at 2, 4, 6, and 12 to 15 months of age. For
      children 7 to 23 months old who have not received previous doses of PCV7,
      administration of a reduced number of doses is recommended. Two doses of PCV7 are
      recommended for children 24 to 59 months old at high risk of invasive
      pneumococcal infection-including children with functional, anatomic, or
      congenital asplenia; infection with human immunodeficiency virus; and other
      predisposing conditions-who have not been immunized previously with PCV7.
      Recommendations have been made for use of 23-valent pneumococcal polysaccharide
      (23PS) vaccine in high-risk children to expand serotype coverage. High-risk
      children should be given vaccines at the earliest possible opportunity. Use of
      antibiotic prophylaxis in children younger than 5 years with functional or
      anatomic asplenia, including children with sickle cell disease, continues to be
      recommended. Children who have not experienced invasive pneumococcal infection
      and have received recommended pneumococcal immunizations may discontinue
      prophylaxis after 5 years of age. The safety and efficacy of PCV7 and 23PS in
      children 24 months or older at moderate or lower risk of invasive pneumococcal
      infection remain under investigation. Current US Food and Drug Administration
      indications are for administration of PCV7 only to children younger than 24
      months. Data are insufficient to recommend routine administration of PCV7 for
      children at moderate risk of pneumococcal invasive infection, including all
      children 24 to 35 months old, children 36 to 59 months old who attend out-of-home
      care, and children 36 to 59 months old who are of Native American (American
      Indian and Alaska Native) or African American descent. However, all children 24
      to 59 months old, regardless of whether they are at low or moderate risk, may
      benefit from the administration of pneumococcal immunizations. Therefore, a
      single dose of PCV7 or 23PS vaccine may be given to children 24 months or older.
      The 23PS is an acceptable alternative to PCV7, although an enhanced immune
      response and probable reduction of nasopharyngeal carriage favor the use of PCV7
      whenever possible.

PMID- 10920170
TI  - American Academy of Pediatrics. Committee on Infectious Diseases. Technical
      report: prevention of pneumococcal infections, including the use of pneumococcal
      conjugate and polysaccharide vaccines and antibiotic prophylaxis.
AB  - Pneumococcal infections are the most common invasive bacterial infections in
      children in the United States. The incidence of invasive pneumococcal infections
      peaks in children younger than 2 years, reaching rates of 228/100,000 in children
      6 to 12 months old. Children with functional or anatomic asplenia (including
      sickle cell disease [SCD]) and children with human immunodeficiency virus
      infection have pneumococcal infection rates 20- to 100-fold higher than those of
      healthy children during the first 5 years of life. Others at high risk of
      pneumococcal infections include children with congenital immunodeficiency;
      chronic cardiopulmonary disease; children receiving immunosuppressive
      chemotherapy; children with immunosuppressive neoplastic diseases; children with
      chronic renal insufficiency, including nephrotic syndrome; children with
      diabetes; and children with cerebrospinal fluid leaks. Children of Native
      American (American Indian and Alaska Native) or African American descent also
      have higher rates of invasive pneumococcal disease. Outbreaks of pneumococcal
      infection have occurred with increased frequency in children attending out-of
      home care. Among these children, nasopharyngeal colonization rates of 60% have
      been observed, along with pneumococci resistant to multiple antibiotics. The
      administration of antibiotics to children involved in outbreaks of pneumococcal
      disease has had an inconsistent effect on nasopharyngeal carriage. In contrast,
      continuous penicillin prophylaxis in children younger than 5 years with SCD has
      been successful in reducing rates of pneumococcal disease by 84%. Pneumococcal
      polysaccharide vaccines have been recommended since 1985 for children older than
      2 years who are at high risk of invasive disease, but these vaccines were not
      recommended for younger children and infants because of poor antibody response
      before 2 years of age. In contrast, pneumococcal conjugate vaccines (Prevnar)
      induce proposed protective antibody responses (>.15 microg/mL) in >90% of infants
      after 3 doses given at 2, 4, and 6 months of age. After priming doses,
      significant booster responses (ie, immunologic memory) are apparent when
      additional doses are given at 12 to 15 months of age. In efficacy trials, infant
      immunization with Prevnar decreased invasive infections by >93% and consolidative
      pneumonia by 73%, and it was associated with a 7% decrease in otitis media and a
      20% decrease in tympanostomy tube placement. Adverse events after the
      administration of Prevnar have been limited to areas of local swelling or
      erythema of 1 to 2 cm and some increase in the incidence of postimmunization
      fever when it is given with other childhood vaccines. Based on data in phase 3
      efficacy and safety trials, the US Food and Drug Administration has provided an
      indication for the use of Prevnar in children younger than 24 months.

PMID- 10920171
TI  - Pioneers in the scientific study of neonatal jaundice and kernicterus.
AB  - Neonatal jaundice must have been noticed by caregivers through the centuries, but
      the scientific description and study of this phenomenon seem to have started in
      the last half of the 18th century. In 1785 Jean Baptiste Thimotee Baumes was
      awarded a prize from the University of Paris for his work describing the clinical
      course in 10 jaundiced infants. The work by Jaques Hervieux, which he defended
      for his doctor of medicine degree in 1847, was, in many respects, a landmark. He
      had autopsied 44 jaundiced infants and apparently had clinical observations on
      many others. His descriptions of pathoanatomical findings were very detailed and
      systematic. A number of his clinical observations are still thought to be
      accurate today, such as the essentially benign nature of neonatal jaundice in
      most cases, the appearance of neonatal jaundice during the first 2 to 4 days of
      life as well as its disappearance within 1 to 2 weeks, and the cephalocaudal
      progression of jaundice. He described jaundice of the brain in 31 of his 44
      autopsied cases, with variable intensity of staining. Johannes Orth was an
      assistant to the famous Virchow in Berlin, when in 1875 he published the results
      of an autopsy of a jaundiced term infant. The brain was notable for an intense
      yellow staining of the basal ganglia, the wall of the third ventricle, the
      hippocampus, and the central parts of the cerebellum. While the contribution of
      Orth was limited to this single case report, in 1903 Christian Schmorl presented
      the results of his autopsies of 120 jaundiced infants to the German Society for
      Pathology. All of these infants' brains were jaundiced, but only 6 cases
      demonstrated a staining phenomenon similar to that previously described by Orth.
      Schmorl coined the term kernicterus (jaundice of the basal ganglia) for this
      staining pattern. Although the following century of scientific study has added an
      enormous amount of information about the epidemiology and pathophysiology of
      neonatal jaundice and kernicterus, the contributions of Hervieux, Orth, and
      Schmorl will undoubtedly continue to be seen as historical landmarks in our quest
      for understanding of these phenomena.

PMID- 10920172
TI  - The value of first-day bilirubin measurement in predicting the development of
      significant hyperbilirubinemia in healthy term newborns.
AB  - OBJECTIVE: The recognition, follow-up, and early treatment of neonatal jaundice
      has become more difficult, since the earlier discharge of newborns from hospitals
      has become common practice. This prospective study was undertaken to identify the
      newborns at risk for developing significant hyperbilirubinemia later during the
      first days of life by measuring the serum bilirubin levels of the first 5 days of
      life to determine the critical predictive serum bilirubin value on the first day
      of life. METHODOLOGY: A total of 498 healthy term newborns were followed with
      daily serum total bilirubin measurements for the first 5 days of life, and cases
      with serum bilirubin levels of >/=17 mg/dL after 24 hours of life were defined to
      have significant hyperbilirubinemia. RESULTS: No newborns had a serum total
      bilirubin level of >/=17 mg/dL in the first 72 hours of life. Sixty of 498 cases
      (12.05%) had significant hyperbilirubinemia after 72 hours of life, and these
      cases had significantly higher bilirubin levels than those who did not develop
      significant hyperbilirubinemia on each of the first 5 days' measurements. Of the
      206 newborns who had a serum bilirubin level of >/=6 mg/dL in the first 24 hours,
      54 (26.21%) developed significant hyperbilirubinemia, whereas only 6 of the 292
      newborns (2.05%) who had a serum bilirubin level of <6 mg/dL on the first day
      developed significant hyperbilirubinemia. A mean serum bilirubin level of >/=6
      mg/dL on the first day had the highest sensitivity (90%). At this critical serum
      bilirubin value, the negative predictive value was very high (97.9%) and the
      positive predictive value was fairly low (26.2%). Furthermore, because no cases
      with a serum bilirubin level of <6 mg/dL in the first 24 hours of life required a
      subsequent phototherapy treatment and because all of those infants requiring a
      phototherapy treatment with serum bilirubin levels of >/=20 mg/dL were just among
      the cases whose first-day bilirubin levels were >/=6 mg/dL, the critical
      bilirubin level of 6 mg/dL on the first day made it possible, with the highest
      (100%) sensitivity and negative predictive value, to definitely predict all of
      the infants who would have a bilirubin level of >20 mg/dL, requiring a
      phototherapy treatment later during the first days of life. CONCLUSIONS: A serum
      bilirubin measurement and the use of the critical bilirubin level of 6 mg/dL in
      the first 24 hours of life will predict nearly all of the term newborns who will
      have significant hyperbilirubinemia and will determine all those who will require
      a phototherapy treatment later during the first days of life.

PMID- 10920173
TI  - Noninvasive measurement of total serum bilirubin in a multiracial predischarge
      newborn population to assess the risk of severe hyperbilirubinemia.
AB  - BACKGROUND: Jaundice in near-term and term newborns is a frequent diagnosis that
      may prompt hospital readmission in the first postnatal week. Hyperbilirubinemia,
      when excessive, can lead to potentially irreversible bilirubin-induced
      neurotoxicity. Predischarge risk assessment (at 24-72 hours of age) for
      subsequent excessive hyperbilirubinemia is feasible by a laboratory-based assay
      of total serum bilirubin (TSB). Hypothesis. Noninvasive, transcutaneous, point-of
      care measurement of transcutaneous bilirubin (TcB) predischarge by
      multiwavelength spectral analysis, using a portable BiliCheck device (SpectRx
      Inc, Norcross, GA), is clinically equivalent to measurement of TSB in a diverse,
      multiracial term and near-term newborn population and predictive of subsequent
      hyperbilirubinemia. METHODOLOGY: We evaluated a hand-held device that uses
      multiwavelength spectral reflectance analysis to measure TcB (BiliCheck). The
      study population (490 term and near-term newborns) was racially diverse (59.1%
      white, 29.5% black, 3.46% Hispanic, 4.48% Asian, and 3.46% other) and was
      evaluated at 2 separate institutions using multiple (11) devices. The postnatal
      age ranged from 12 to 98 hours and the ranges of birth weights and gestational
      ages were 2000 to 5665 g and 35 to 42 weeks, respectively. All transcutaneous
      evaluations were performed contemporaneously and paired with a heelstick TSB
      measurement. All TSB assays were performed by high performance liquid
      chromatography, as well as by diazo dichlorophenyldiazonium tetrafluoroborate
      techniques. RESULTS: TSB values ranged from .2 to 18.2 mg/dL (mean +/- standard
      deviation: 7.65 +/- 3.35 mg/dL). The overall correlation of TSB (by high
      performance liquid chromatography technique) to TcB (by BiliCheck devices) was
      linear and statistically significant (r =.91; r(2) =.83; TcB =.84; TSB = +.75;
      standard error of regression line = 1.38; P <.001; n = 490 infants; 1788
      samples). Similar regression statistics were evident in subset populations
      categorized by race (white: r =.91 [n = 289 infants]; black: r =.91 [n = 145
      infants]) as well as by gestation (term: r =. 91 [n = 1625 samples]; near-term: r
      =.89 [n = 163 samples]). Intradevice precision was determined to be.59 mg/dL (2-3
      measurements per infant with 1 device; n = 210 infants; 510 samples in a separate
      subset). Interdevice evaluation of 11 devices determined the precision to be.68
      mg/dL (2-4 devices used for measurements per patient). In 23 of 419 of the study
      population infants who were in the 24- to 72-hour age range, the predischarge TSB
      values designated them to be at high risk for subsequent excessive
      hyperbilirubinemia (above the 95th percentile track on the hour-specific
      bilirubin nomogram). For these infants, the paired BiliCheck TcB values were all
      above the 75th percentile track (negative predictive value = 100%; positive
      predictive value = 32. 86%; sensitivity = 100%; specificity = 88.1%; likelihood
      ratio = 8. 43). CONCLUSIONS: Our data demonstrate the accuracy and
      reproducibility of the predischarge BiliCheck measurements in term and near-term
      newborn infants of diverse races and ethnicities. Infants with predischarge
      BiliCheck values above the 75th percentile of hour-specific TSB values on the
      bilirubin nomogram may be considered to be at high risk for subsequent excessive
      hyperbilirubinemia. Further studies are needed to assess the efficacy of this
      technique in preterm infants, those undergoing phototherapy, and those with TSB
      values of >/=15 mg/dL (>/=256 micromol/L).

PMID- 10920174
TI  - Bacterial colonization of toys in neonatal intensive care cots.
AB  - OBJECTIVES: To investigate the bacteria and fungi contaminating toys in neonatal
      intensive care unit (NICU) cots, the colonization rates, and factors that
      influence them. METHODS: A cross-sectional, longitudinal bacteriologic survey of
      all toys in the cots of infants in an NICU. All the toys in an infant's cot were
      cultured weekly for 4 weeks. Data were collected on the infant's postnatal age,
      the type of cot, whether humidity was added, characteristics of the toy, and any
      infant infections. RESULTS: Over the 4-week period, there were 86 cultures from
      34 toys of 19 infants. Bacteria were grown from 84/86 (98%): 84 of the cultures
      grew coagulase-negative Staphylococcus, 50 Micrococcus sp, 21 Bacillus sp, 13
      methicillin-resistant Staphylococcus aureus, 12 diphtheroids, 4 group B
      streptococcus, 3 S aureus, 3 nonhemolytic streptococci, 3 group D streptococci, 4
      alpha-hemolytic streptococci, and 2 coliforms. None grew fungi. The colonization
      rate did not differ with cot type, presence of humidity, size of the toy, toy
      fiber length, or the fluffiness score. Eight (42%) of the infants had positive
      blood culture results and 5/8 of the isolates (63%) were of the same type as that
      colonizing their corresponding toy. IMPLICATIONS: With time, all the toys in NICU
      cots became colonized with bacteria. Many were potentially pathogenic. Toys may
      be reservoirs for potential infantile nosocomial sepsis. infant, newborn, toys,
      infection, neonatal intensive care.

PMID- 10920175
TI  - Phlebotomy overdraw in the neonatal intensive care nursery.
AB  - OBJECTIVE: Because blood loss attributable to laboratory testing is the primary
      cause of anemia among preterm infants during the first weeks of life, we
      quantified blood lost attributable to phlebotomy overdraw, ie, excess that might
      be avoided. We hypothesized that phlebotomy overdraw in excess of that requested
      by the hospital laboratory was a common occurrence, that clinical factors
      associated with excessive phlebotomy loss would be identified, and that some of
      these factors are potentially correctable. DESIGN, OUTCOME MEASURES, AND
      ANALYSIS: Blood samples drawn for clinical purposes from neonates cared for in
      our 2 neonatal special care units were weighed, and selected clinical data were
      recorded. The latter included the test performed; the blood collection container
      used; the infant's location (ie, neonatal intensive care unit [NICU] and
      intermediate intensive care unit); the infant's weight at sampling; and the
      phlebotomist's level of experience, work shift, and clinical role. Data were
      analyzed by univariate and multivariate procedures. Phlebotomists included
      laboratory technicians stationed in the neonatal satellite laboratory,
      phlebotomists assigned to the hospital's central laboratory, and neonatal staff
      nurses. Phlebotomists were considered experienced if they had worked in the
      nursery setting for >1 year. Blood was sampled from a venous or arterial catheter
      or by capillary stick from a finger or heel. Blood collection containers were
      classified as tubes with marked fill-lines imprinted on the outside wall, tubes
      without fill-lines, and syringes. Infants were classified by weight into 3
      groups: <1 kg, 1 to 2 kg, and >2 kg. The volume of blood removed was calculated
      by subtracting the weight of the empty collection container from that of the
      container filled with blood and dividing by the specific gravity of blood, ie,
      1.050 g/mL. The volume of blood withdrawn for individual laboratory tests was
      expressed as a percentage of the volume requested by the hospital laboratory.
      RESULTS: The mean (+/- standard error of the mean) volume of blood drawn for the
      578 tests drawn exceeded that requested by the hospital laboratory by 19.0% +/-
      1.8% per test. The clinical factors identified as being significantly associated
      with greater phlebotomy overdraw in the multiple regression model included: 1)
      collection in blood containers without fill-lines; 2) lighter weight infants; and
      3) critically ill infants being cared for in the NICU. Because the overall R(2)
      of the multiple regression for these 3 clinical factors was only.24, the random
      factor of individual phlebotomist was added to the model. This model showed that
      there was a significant variation in blood overdraw among individual
      phlebotomists, and as a result, the overall R(2) increased to.52. An additional
      subset analysis involving 2 of the 3 groups of blood drawers (ie, hospital and
      neonatal laboratory phlebotomists) examining the effect of work shift,
      demonstrated that there was significantly greater overdraw for blood samples
      obtained during the evening shift, compared with the day shift when drawn using
      unmarked tubes for the group of heavier infants cared for in the NICU.
      CONCLUSION: Significant volumes of blood loss are attributable to overdraw for
      laboratory testing. This occurrence likely exacerbates the anemia of prematurity
      and may increase the need for transfusions in some infants. Attempts should be
      made to correct the factors involved. Common sense suggests that blood samples
      drawn in tubes with fill-lines marked on the outside would more closely
      approximate the volumes requested than those without. Conversely, the use of
      unmarked tubes could lead to phlebotomy overdraw because phlebotomists may
      overcompensate to avoid having to redraw the sample because of an insufficient
      volume for analysis. We were surprised to observe that the lightest and most
      critically ill infants experienced the greatest blood overdraw. (ABSTRACT
      TRUNCATED)

PMID- 10920176
TI  - Booster seat use and reasons for nonuse.
AB  - BACKGROUND: Many children 4 to 9 years old are inappropriately restrained in
      vehicles and are at risk for injury in crashes. OBJECTIVES: This study was
      undertaken to determine the rate of booster seat use and the reasons for nonuse.
      METHODS: Observations were conducted at a random sample of day care centers, and
      drivers of unrestrained children 4 to 8 years old were interviewed to determine
      the reasons for lack of booster seat use. RESULTS: Observations were conducted on
      149 children. Shoulder belt use significantly increased with the age of the
      child; 28.3% of 4-year-olds and 70.0% of 6- to 8-year-olds used lap-shoulder
      belts. Overall, 27.7% of children in the target age group used booster seats;
      only 10% of children 6 to 8 years old were restrained with booster seats. Booster
      seat use decreased when there were 3 or more passengers in the vehicle. The most
      common reason for lack of booster seat use was that parents thought the child was
      large enough to use the regular lap-shoulder belt system, or problems with
      attempting to use the seat in the vehicle. More than one half of parents who were
      not using booster seats at the time of the survey reported owning seats.
      CONCLUSION: This study indicates that parental misconceptions about size and
      safety of regular restraint equipment are the most common reason that children
      are not appropriately restrained in vehicles. This information can be used to
      guide community intervention programs.

PMID- 10920177
TI  - A new look at intrauterine growth and the impact of race, altitude, and gender.
AB  - BACKGROUND: Growth curves described in the 1960s are used to classify neonate
      intrauterine growth as normal or abnormal. Our objective was to determine whether
      continued use of these curves is appropriate. METHODS: From 1996 to 1998, we
      collected birth weight, length, head circumference, estimated gestational age
      (EGA), gender, race, and place of birth (<4,000 feet or >/=4,000 feet) on 27 229
      neonates to evaluate the effects of each on intrauterine growth and the diagnoses
      of small for gestational age (SGA) and large for gestational age (LGA). We
      compared the gestation-specific growth parameters derived from our sample with
      those reported in 1966 and 1969. RESULTS: Gestational age had the largest
      influence on each growth parameter. Race and gender both had effects on birth
      weight. Female neonates were smaller than male neonates, and black neonates were
      smaller than Hispanic and white neonates at each EGA. For neonates with an EGA
      <30 weeks, our data had a smaller variance and lower average weights, lengths,
      and head circumferences than those reported in 1966 and in 1969. For neonates >36
      weeks, the variance was similar, but our curves showed that neonates in our
      sample were larger and heavier. Use of the older growth curves to classify
      neonates as SGA, LGA, and appropriate for gestational age (AGA) led to
      significantly different rates of each by gender and race. CONCLUSIONS:
      Intrauterine growth patterns previously described and commonly used to classify
      neonates as AGA are inaccurate for use in current populations and lead to gender-
      and race-specific diagnoses of SGA and LGA that are misleading. neonates, growth,
      race, gender.

PMID- 10920178
TI  - Sexual behavior change among human immunodeficiency virus-infected adolescents
      with hemophilia. Adolescent Hemophilia Behavioral Intervention Evaluation Project
      Study Group.
AB  - PURPOSE: To determine the factors associated with the adoption or maintenance of
      consistent safer sexual behaviors among human immunodeficiency virus-positive
      adolescents and young adults with hemophilia. METHODS: One hundred eleven
      adolescents at 10 hemophilia care sites participated in an intervention program
      designed to increase safer sexual behaviors (abstinence, condom use, or
      nonpenetrative behavior). The theory-based intervention spanned 1 year.
      Adolescents attended individual sessions, small group activities, and an
      intensive group retreat. RESULTS: Patients who maintained or improved safer
      sexual behaviors were compared with those who relapsed or did not improve.
      Logistic regression analyses found that improvement and maintenance of safer
      sexual behavior were significantly associated with perceived peer support for
      outercourse (odds ratio [OR]: 5.47; confidence interval [CI]: 1.4-20.8),
      perceived peer support for abstinence (OR: 5.08; CI: 1.2-20.1), and decreased
      general emotional distress (OR: 4.65; CI: 1.04-20.6). Perceived health status and
      previous sexual behavior were unrelated to change in safer sexual behavior.
      CONCLUSIONS: These longitudinal data indicate that improvement and maintenance of
      safer sexual behavior among adolescents during an intervention is strongly
      associated with perceptions of peer support for safer sex and lesser degrees of
      emotional distress. Programs for human immunodeficiency virus-infected
      adolescents may require developmentally appropriate social and psychological
      approaches to impact peer norms and emotional well-being.

PMID- 10920179
TI  - Depressive symptoms and cigarette smoking predict development and persistence of
      sleep problems in US adolescents.
AB  - OBJECTIVE: To evaluate factors related to the development and persistence of
      adolescent sleep problems. METHODS: In this longitudinal, population-based study,
      the Teenage Attitudes and Practices Survey was administered by telephone to 7960
      adolescents (3921 girls and 4039 boys) 12 to 18 years old in 1989 and at follow
      up in 1993. Sleep problems at both time points were assessed using a single item
      on the Teenage Attitudes and Practices Survey. Those who responded that they
      "often or sometimes" had trouble going to sleep or staying asleep during the past
      12 months were categorized as reporting sleep problems, whereas those who
      responded "often" were categorized as having frequent sleep problems. Multiple
      logistic regression analyses were used to identify baseline characteristics
      predictive of the development and persistence of sleep problems or frequent sleep
      problems, respectively, from baseline to follow-up. RESULTS: Of the 4866
      adolescents without sleep problems at baseline, 28% developed sleep problems by
      1993, and 9% developed frequent sleep problems. Of the 3094 adolescents who
      reported sleep problems at baseline, 52% reported sleep problems in 1993, and 21%
      reported frequent sleep problems. Female sex and notable depressive symptoms were
      associated with the development and persistence of sleep problems and frequent
      sleep problems at follow-up. Cigarette smoking status showed a dose-response
      relationship with development of sleep problems and frequent sleep problems, and
      with persistence of frequent sleep problems at follow-up. CONCLUSION: The
      reduction of depressive symptoms and cigarette smoking among adolescents are
      important factors to consider in prevention and treatment efforts focused on
      adolescent sleep problems.

PMID- 10920180
TI  - Predictors of change in the functional status of children with human
      immunodeficiency virus infection.
AB  - OBJECTIVE: The purpose of this study was to identify important clinical
      predictors of change in the functional status of children with perinatally
      acquired human immunodeficiency virus (HIV) infection. METHODS: Children who were
      perinatally exposed to HIV underwent evaluation of growth, nutritional, and
      functional status parameters as part of a prospective study of HIV and nutrition
      in children. The main outcome measures for HIV-infected children were change over
      time in: 1) Total Health, 2) General Health, and 3) Responsiveness as measured by
      the Functional Status II(R) (FSII[R]). Candidate predictors included
      anthropometric measurements, social factors, HIV disease stage, CD4 T lymphocyte
      count, medications, and other clinical markers of illness. RESULTS: The parents
      or legal guardians of 35 perinatally HIV-infected children completed 2 FSII(R)
      surveys over a mean of 16 months. Functional Status scores were significantly
      correlated with number of times and days hospitalized in the past 6 months and
      with illness at the time of baseline evaluation. Functional status declined
      overtime on all 3 scales; however, only the change in Total Health score was
      statistically significant. Total, General Health, and Responsiveness scores
      declined by >/=5 points in 20.0%, 17.1%, and 14.3% of children, respectively.
      Significant univariate predictors of change in at least 1 component of the
      functional status survey included race, guardianship, height z score,
      prescription of antiviral medications other than antiretrovirals, and illness at
      time of baseline evaluation. In multivariate models, adjusting for baseline score
      and biologic relationship of guardian completing survey, significant predictors
      of a decline in Total Health scores included non-white race and lower baseline
      height z score. The General Health score declined with lower baseline absolute
      CD4 count and lower baseline height z score. Finally, Responsiveness scores
      declined in children whose guardian was their biologic parent and in children
      with lower baseline height z scores. CONCLUSION: The FSII(R) questionnaire
      correlates with other markers of disease severity in children with HIV infection.
      Growth parameters, immune status, and social factors are important predictors of
      functional status in HIV-infected children.

PMID- 10920181
TI  - Early cognitive and motor development among infants born to women infected with
      human immunodeficiency virus. Women and Infants Transmission Study Group.
AB  - OBJECTIVE: To examine the frequency, timing, and factors associated with abnormal
      cognitive and motor development during the first 30 months of life in infants
      born to women infected with human immunodeficiency virus type 1 (HIV-1). METHODS:
      Serial neurodevelopmental assessment was performed with 595 infants born to women
      infected with HIV-1 in a multicenter, prospective, natural history cohort study.
      Survival analysis methods were used to evaluate 6 outcome events related to
      abnormal cognitive and motor growth (time to confirmed drop of 1 SD, time to
      first score <69, and time to confirmed drop of 2 SD) in Bayley Scales of Infant
      Development Mental Developmental Index (MDI) and Psychomotor Developmental Index
      (PDI) scores among infected (n = 114) and uninfected (n = 481) infants.
      Proportional hazards modeling was used to evaluate the effects of HIV infection
      status, prematurity, prenatal exposure to illicit drugs, maternal educational
      attainment, and primary language. RESULTS: HIV-1 infection was significantly
      associated with increased risk for all outcome events related to abnormal mental
      and motor growth. Differences between infected and uninfected infants were
      apparent by 4 months of age. Prematurity was associated with increased risk for
      MDI <69 and PDI <69. Maternal education of <9 completed years was associated with
      increased risk for MDI <69. Neither prenatal exposure to illicit drugs nor
      primary language other than English was associated with abnormal development.
      CONCLUSION: A significant proportion of infants with HIV-1 infection show early
      and marked cognitive and motor delays or declines that may be important early
      indicators of HIV disease progression. These abnormalities are independent of
      other risk factors for developmental delay.

PMID- 10920182
TI  - Association of adolescent cigar use with other high-risk behaviors.
AB  - OBJECTIVES: To describe the association of cigar use with use of cigarettes,
      smokeless tobacco, and alcohol among adolescents; and to examine the association
      of self-esteem, physical activity, and use of tobacco promotional items with
      cigar use. METHODS: A cross-sectional study of 7104 girls and 5499 boys 10 to 15
      years of age in 1997. Data were collected from self-report questionnaires.
      RESULTS: The prevalence of cigar use increased with age among both girls and
      boys. Among 11-year-olds, only 1% of girls and 3% of boys had used a cigar,
      whereas among 15-year-olds, 11% of girls and 25% of boys had used a cigar. Cigar
      users were much more likely than nonusers to have experimented with cigarettes
      (girls, odds ratio [OR]: 23.6; 95% confidence interval [CI]: 17.2-32.3; boys, OR:
      21.3; 95% CI: 17.1-26.6), smokeless tobacco (girls, OR: 7.5; 95% CI: 4. 5-12.4;
      boys, OR: 13.0; 95% CI: 9.8-17.4), and alcohol (girls, OR: 6. 6; 95% CI: 4.8-9.1;
      boys, OR: 6.8; 95% CI: 5.3-8.8). There was a strong association between cigar use
      and binge drinking, especially among boys (girls, OR: 11.6; 95% CI: 7.9-16.9;
      boys, OR: 34.8; 95% CI: 19.4-62.3). Cigar users reported more hours of weekly
      physical activity than did nonusers. Additionally, cigar users were more likely
      to report high social self-esteem and to possess a tobacco promotional item.
      CONCLUSIONS: Adolescents who use cigars are more likely to use other tobacco
      products and alcohol, to report high social self-esteem, and to possess tobacco
      promotional items. Health care professionals and teachers should include cigar
      use in discussions with adolescents addressing substance use.

PMID- 10920183
TI  - Kawasaki disease: A brief history.
AB  - Tomisaku Kawasaki published the first English-language report of 50 patients with
      Kawasaki disease (KD) in 1974. Since that time, KD has become the leading cause
      of acquired heart disease among children in North America and Japan. Although an
      infectious agent is suspected, the cause remains unknown. However, significant
      progress has been made toward understanding the natural history of the disease
      and therapeutic interventions have been developed that halt the immune-mediated
      destruction of the arterial wall. We present a brief history of KD, review
      progress in research on the disease, and suggest avenues for future study.
      Kawasaki saw his first case of KD in January 1961 and published his first report
      in Japanese in 1967. Whether cases existed in Japan before that time is currently
      under study. The most significant controversy in the 1960s in Japan was whether
      the rash and fever sign/symptom complex described by Kawasaki was connected to
      subsequent cardiac complications in a number of cases. Pathologist Noboru Tanaka
      and pediatrician Takajiro Yamamoto disputed the early assertion of Kawasaki that
      KD was a self-limited illness with no sequelae. This controversy was resolved in
      1970 when the first Japanese nationwide survey of KD documented 10 autopsy cases
      of sudden cardiac death after KD. By the time of the first English-language
      publication by Kawasaki in 1974, the link between KD and coronary artery
      vasculitis was well-established. KD was independently recognized as a new and
      distinct condition in the early 1970s by pediatricians Marian Melish and Raquel
      Hicks at the University of Hawaii. In 1973, at the same Hawaiian hospital,
      pathologist Eunice Larson, in consultation with Benjamin Landing at Los Angeles
      Children's Hospital, retrospectively diagnosed a 1971 autopsy case as KD. The
      similarity between KD and infantile periarteritis nodosa (IPN) was apparent to
      these pathologists, as it had been to Tanaka earlier. What remains unknown is the
      reason for the simultaneous recognition of this disease around the world in the
      1960s and 1970s. There are several possible explanations. KD may have been a new
      disease that emerged in Japan and emanated to the Western World through Hawaii,
      where the disease is prevalent among Asian children. Alternatively, KD and IPN
      may be part of the spectrum of the same disease and clinically mild KD
      masqueraded as other diseases, such as scarlet fever in the preantibiotic era.
      Case reports of IPN from Western Europe extend back to at least the 19th century,
      but, thus far, cases of IPN have not been discovered in Japan before World War
      II. Perhaps the factors responsible for KD were introduced into Japan after the
      World War II and then reemerged in a more virulent form that subsequently spread
      through the industrialized Western world. It is also possible that improvements
      in health care and, in particular, the use of antibiotics to treat infections
      caused by organisms including toxin-producing bacteria reduced the burden of
      rash/fever illness and allowed KD to be recognized as a distinct clinical entity.
      Itsuzo Shigematsu, Hiroshi Yanagawa, and colleagues have conducted 14 nationwide
      surveys in Japan. These have indicated that: 1) KD occurred initially in
      nationwide epidemics but now occurs in regional outbreaks; 2) there are
      approximately 5,000 to 6,000 new cases each year; 3) current estimates of
      incidence rates are 120 to 150 cases per 100,000 children <5 years old; 4) KD is
      1.5 times more common in males and 85% of cases occur in children <5 years old;
      and 5) the recurrence rate is low (4%). In 1978, David Morens at the Centers for
      Disease Control and Prevention published a case definition based on Kawasaki's
      original criteria. The Centers for Disease Control and Prevention developed a
      computerized database in 1984, and a passive reporting system currently exists in
      22 states. Regional investigations and national surveys suggest an annual
      incidence of 4 to 15 cases per 100 000 children <5 years o

PMID- 10920184
TI  - Chickenpox attributable to a vaccine virus contracted from a vaccinee with
      zoster.
AB  - Five months after 2 siblings were immunized with varicella vaccine, 1 developed
      zoster. Two weeks later the second sibling got a mild case of chicken pox. Virus
      isolated from the latter was found to be vaccine type. Thus, the vaccine strain
      was transmitted from the vaccinee with zoster to his sibling. Vaccinees who later
      develop zoster must be considered contagious. varicella-zoster, zoster, vaccine,
      transmission, rash, PstI.

PMID- 10920186
TI  - Panhandle PCR for cDNA: a rapid method for isolation of MLL fusion transcripts
      involving unknown partner genes.
AB  - Identifying translocations of the MLL gene at chromosome band 11q23 is important
      for the characterization and treatment of leukemia. However, cytogenetic analysis
      does not always find the translocations and the many partner genes of MLL make
      molecular detection difficult. We developed cDNA panhandle PCR to identify
      der(11) transcripts regardless of the partner gene. By reverse transcribing first
      strand cDNAs with oligonucleotides containing coding sequence from the 5' MLL
      breakpoint cluster region at the 5' ends and random hexamers at the 3' ends,
      known MLL sequence was attached to the unknown partner sequence. This enabled the
      formation of stem-loop templates with the fusion point of the chimeric transcript
      in the loop and the use of MLL primers in two-sided PCR. The assay was validated
      by detection of the known fusion transcript and the transcript from the normal
      MLL allele in the cell line MV4-11. cDNA panhandle PCR then was used to identify
      the fusion transcripts in two cases of treatment-related acute myeloid leukemia
      where the karyotypes were normal and the partner genes unknown. cDNA panhandle
      PCR revealed a fusion of MLL with AF-10 in one case and a fusion of MLL with ELL
      in the other. Alternatively spliced transcripts and exon scrambling were
      detectable by the method. Leukemias with normal karyotypes may contain cryptic
      translocations of MLL with a variety of partner genes. cDNA panhandle PCR is
      useful for identifying MLL translocations and determining unknown partner
      sequences in the fusion transcripts.

PMID- 10920185
TI  - A role for transcriptional repression of p21CIP1 by c-Myc in overcoming
      transforming growth factor beta -induced cell-cycle arrest.
AB  - c-Myc plays a vital role in cell-cycle progression. Deregulated expression of c
      Myc can overcome cell-cycle arrest in order to promote cellular proliferation.
      Transforming growth factor beta (TGFbeta) treatment of immortalized human
      keratinocyte cells inhibits cell-cycle progression and is characterized by down
      regulation of c-Myc followed by up-regulation of p21(CIP1). A direct role of c
      Myc in this pathway was demonstrated by the observation that ectopic expression
      of c-Myc overcame the cell-cycle block induced by TGFbeta treatment. The
      induction of p21(CIP1) transcription by TGFbeta was blocked in human keratinocyte
      cells stably expressing c-Myc. Furthermore, overexpression of c-Myc in NIH 3T3
      cells repressed the basal levels of p21(CIP1) mRNA. Repression of p21(CIP1)
      transcription by c-Myc occurred at the promoter level in a region near the start
      site of transcriptional initiation and was independent of histone deacetylase
      activity. These data suggest that the down-regulation of c-Myc after TGFbeta
      signaling is important for subsequent regulation of p21(CIP1) and cell-cycle
      inhibition. Thus, repression of the cell-cycle inhibitory gene p21(CIP1) plays a
      role in c-Myc-dependent cell-cycle progression.

PMID- 10920187
TI  - A delta 9 desaturase gene with a different substrate specificity is responsible
      for the cuticular diene hydrocarbon polymorphism in Drosophila melanogaster.
AB  - Drosophila melanogaster cuticular pheromones consist of unsaturated hydrocarbons
      with at least one double bond in position 7: 7 tricosene (T) in males and 7,11
      heptacosadiene (HD) in females. However, in many African populations like the Tai
      strain, females possess low levels of 7,11 HD and high levels of its positional
      isomer 5,9 HD. We have previously isolated a desaturase gene, desat1, from the
      Canton-S strain (CS), a 7,11 HD-2-rich morph of D. melanogaster. This desaturase
      is located in 87C, a locus that has been involved in the difference between 7,11
      HD and 5,9 HD morphs. Therefore, we have searched for different desaturase
      isoforms in both strains. We first cloned desat1 in the Tai strain and report
      here functional expression of desat1 in CS and Tai. In both strains, the Desat1
      enzymes have the same Delta9 specificity and preferentially use palmitate as a
      substrate, leading to the synthesis of omega7 fatty acids. Also found was a
      desaturase sequence, named desat2, with a homologous catalytic domain and a
      markedly different N-terminal domain compared with desat1. In CS genome, it lies
      3.8 kb upstream of desat1 and is not transcribed in either sex. In the Tai
      strain, it is expressed only in females and acts preferentially on myristate,
      leading to the synthesis of omega5 fatty acids. We suggest, therefore, that
      desat2 might play a control role in the biosynthesis of 5,9 HD hydrocarbons in
      Tai females and could explain the dienic hydrocarbon polymorphism in D.
      melanogaster.

PMID- 10920188
TI  - A46R and A52R from vaccinia virus are antagonists of host IL-1 and toll-like
      receptor signaling.
AB  - Poxviruses employ many strategies to evade and neutralize the host immune
      response. In this study, we have identified two vaccinia virus ORFs, termed A46R
      and A52R, that share amino acid sequence similarity with the Toll/IL-1 receptor
      (TIR) domain, a motif that defines the IL-1/Toll-like receptor (TLR) superfamily
      of receptors, which have a key role in innate immunity and inflammation. When
      expressed in mammalian cells, the protein products of both ORFs were shown to
      interfere specifically with IL-1 signal transduction. A46R partially inhibited IL
      1-mediated activation of the transcription factor NFkappaB, and A52R potently
      blocked both IL-1- and TLR4-mediated NFkappaB activation. MyD88 is a TIR domain
      containing adapter molecule known to have a central role in both IL-1 and TLR4
      signaling. A52R mimicked the dominant-negative effect of a truncated version of
      MyD88 on IL-1, TLR4, and IL-18 signaling but had no effect on MyD88-independent
      signaling pathways. Therefore, A46R and A52R are likely to represent a mechanism
      used by vaccinia virus of suppressing TIR domain-dependent intracellular
      signaling.

PMID- 10920189
TI  - Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory
      epithelia.
AB  - Many pathogens causing diarrhea do so by modulating ion transport in the gut.
      Respiratory pathogens are similarly associated with disturbances of fluid balance
      in the respiratory tract, although it is not known whether they too act by
      altering epithelial ion transport. Here we show that influenza virus A/PR/8/34
      inhibits the amiloride-sensitive Na(+) current across mouse tracheal epithelium
      with a half-time of about 60 min. We further show that the inhibitory effect of
      the influenza virus is caused by the binding of viral hemagglutinin to a cell
      surface receptor, which then activates phospholipase C and protein kinase C.
      Given the importance of epithelial Na(+) channels in controlling the amount of
      fluid in the respiratory tract, we suggest that down-regulation of Na(+) channels
      induced by influenza virus may play a role in the fluid transport abnormalities
      that are associated with influenza infections.

PMID- 10920190
TI  - Inhibition of IL-2-induced Jak-STAT signaling by glucocorticoids.
AB  - Glucocorticoids (GCs) are potent anti-inflammatory agents that block cytokine
      production. We investigated whether GCs also block cytokine signaling via the
      Janus kinase (Jak)-signal transducer and activator of transcription (STAT)
      pathway. Dexamethasone inhibited IL-2-induced DNA binding, tyrosine
      phosphorylation, and nuclear translocation of Stat5 in primary T cells.
      Inhibition of Stat5 correlated with inhibition of expression of IL-2-inducible
      genes and T cell proliferation. The mechanism of inhibition involved suppression
      of IL-2 receptor and Jak3 expression. Signaling by IL-4, IL-7, and IL-15, which
      use IL-2 receptor components, also was inhibited, indicating a block in T cell
      responses similar to that seen in immunodeficient patients lacking the IL-2
      receptor gamma chain or Jak3. IL-2 signaling also was blocked in patients after
      treatment with GCs, suggesting that inhibition of cytokine signaling contributes
      to the clinical efficacy of these agents. These results identify inhibition of
      Jak-STAT signaling by IL-2 and related cytokines as a novel mechanism of GC
      action and suggest that inhibition of both cytokine production and signaling
      contribute to their therapeutic potency.

PMID- 10920191
TI  - The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic
      therapeutic in murine collagen-induced arthritis.
AB  - The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive
      component of cannabis, was explored in murine collagen-induced arthritis (CIA).
      CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete
      Freund's adjuvant. The CII used was either bovine or murine, resulting in
      classical acute CIA or in chronic relapsing CIA, respectively. CBD was
      administered after onset of clinical symptoms, and in both models of arthritis
      the treatment effectively blocked progression of arthritis. CBD was equally
      effective when administered i.p. or orally. The dose dependency showed a bell
      shaped curve, with an optimal effect at 5 mg/kg per day i.p. or 25 mg/kg per day
      orally. Clinical improvement was associated with protection of the joints against
      severe damage. Ex vivo, draining lymph node cells from CBD-treated mice showed a
      diminished CII-specific proliferation and IFN-gamma production, as well as a
      decreased release of tumor necrosis factor by knee synovial cells. In vitro
      effects of CBD included a dose-dependent suppression of lymphocyte proliferation,
      both mitogen-stimulated and antigen-specific, and the blockade of the Zymosan
      triggered reactive oxygen burst by peritoneal granulocytes. It also was found
      that CBD administration was capable of blocking the lipopolysaccharide-induced
      rise in serum tumor necrosis factor in C57/BL mice. Taken together, these data
      show that CBD, through its combined immunosuppressive and anti-inflammatory
      actions, has a potent anti-arthritic effect in CIA.

PMID- 10920192
TI  - Inversion of stereospecificity of vanillyl-alcohol oxidase.
AB  - Vanillyl-alcohol oxidase (VAO) is the prototype of a newly recognized family of
      structurally related oxidoreductases sharing a conserved FAD-binding domain. The
      active site of VAO is formed by a cavity where the enzyme is able to catalyze
      many reactions with phenolic substrates. Among these reactions is the
      stereospecific hydroxylation of 4-ethylphenol-forming (R)-1-(4'
      hydroxyphenyl)ethanol. During this conversion, Asp-170 is probably critical for
      the hydration of the initially formed p-quinone methide intermediate. By site
      directed mutagenesis, the putative active site base has been relocated to the
      opposite face of the active site cavity. In this way, a change in
      stereospecificity has been achieved. Like native VAO, the single mutants T457E,
      D170A, and D170S preferentially converted 4-ethylphenol to the (R)-enantiomer of
      1-(4'-hydroxyphenyl)ethanol. The double mutants D170A/T457E and D170S/T457E
      exhibited an inverted stereospecificity with 4-ethylphenol. Particularly,
      D170S/T457E was strongly (S)-selective, with an enantiomeric excess of 80%. The
      crystal structure of D170S/T457E, in complex with trifluoromethylphenol, showed a
      highly conserved mode of ligand binding and revealed that the distinctive
      catalytic properties of this mutant are not caused by major structural changes.

PMID- 10920193
TI  - A second, substrate-dependent site of protein import into chloroplasts.
AB  - Chloroplasts must import a large number of proteins from the cytosol. It
      generally is assumed that this import proceeds for all stromal and thylakoid
      proteins in an identical manner and is caused by the operation of two distinctive
      protein import machineries in the outer and inner plastid envelope, which form
      the general import site. Here we show that there is a second site of protein
      translocation into chloroplasts of barley, tobacco, Arabidopsis thaliana, and
      five other tested monocotyledonous and dicotyledonous plant species. This import
      site is specific for the cytosolic precursor of the NADPH:protochlorophyllide
      (Pchlide) oxidoreductase A, pPORA. It couples Pchlide synthesis to pPORA import
      and thereby reduces the actual level of free Pchlide, which, because of its
      photodynamic properties, would be destructive to the plastids. Consequently,
      photoprotection is conferred onto the plant.

PMID- 10920194
TI  - Hyperpolarization-activated calcium channels at the tip of Arabidopsis root
      hairs.
AB  - The root hair elongative growth phase ("tip growth"), like that of other tip
      growing systems such as pollen tubes, algal rhizoids, and fungal hyphae, is
      associated with an apex-high cytosolic free calcium ([Ca(2+)](c)) gradient
      generated by a local Ca(2+) influx at the tip. This gradient has been shown to be
      a fundamental regulator of tip growth. Here, we have performed patch-clamp
      experiments at root hair apices of Arabidopsis thaliana (after localized cell
      wall laser ablation) to characterize the plasma membrane Ca(2+) channels
      implicated in the tip Ca(2+) influx. We have identified a hyperpolarization
      activated Ca(2+) conductance. This conductance is selective for Ca(2+) over K(+)
      and Cl(-) (P(Ca)/P(K) = 15; P(Ca)/P(Cl) = 25) and is fully blocked by < 100
      microM trivalent cations (La(3+), Al(3+), Gd(3+)). The selectivity sequence among
      divalent cations (determined by comparisons of the channel unitary conductance)
      is Ba(2+) > Ca(2+) (22 pS in 10 mM) approximately Mg(2+) > Mn(2+). This
      conductance was operative at typical growing hair apical resting membrane
      potentials. Moreover, it was seen to be down-regulated in growing hair subapical
      regions, as well as at the tip of mature hairs (known not to exhibit Ca(2+)
      influx). We therefore propose that this inward-rectifying Ca(2+) conductance is
      inherently involved in the apical Ca(2+) influx of growing hairs. The observed
      enhancement of the conductance by increased [Ca(2+)](c) may form part of a
      positive feedback system for continued apical Ca(2+) influx during tip growth.

PMID- 10920195
TI  - A sea urchin genome project: sequence scan, virtual map, and additional
      resources.
AB  - Results of a first-stage Sea Urchin Genome Project are summarized here. The
      species chosen was Strongylocentrotus purpuratus, a research model of major
      importance in developmental and molecular biology. A virtual map of the genome
      was constructed by sequencing the ends of 76,020 bacterial artificial chromosome
      (BAC) recombinants (average length, 125 kb). The BAC-end sequence tag connectors
      (STCs) occur an average of 10 kb apart, and, together with restriction digest
      patterns recorded for the same BAC clones, they provide immediate access to
      contigs of several hundred kilobases surrounding any gene of interest. The STCs
      survey >5% of the genome and provide the estimate that this genome contains
      approximately 27,350 protein-coding genes. The frequency distribution and
      canonical sequences of all middle and highly repetitive sequence families in the
      genome were obtained from the STCs as well. The 500-kb Hox gene complex of this
      species is being sequenced in its entirety. In addition, arrayed cDNA libraries
      of >10(5) clones each were constructed from every major stage of embryogenesis,
      several individual cell types, and adult tissues and are available to the
      community. The accumulated STC data and an expanding expressed sequence tag
      database (at present including >12, 000 sequences) have been reported to GenBank
      and are accessible on public web sites.

PMID- 10920196
TI  - Autocatalytic proteolysis of the transcription factor-coactivator C1 (HCF): a
      potential role for proteolytic regulation of coactivator function.
AB  - Site-specific proteolysis is an important biological mechanism for the regulation
      of cellular processes such as gene expression, cell signaling, development, and
      apoptosis. In transcriptional regulation, specific proteolysis regulates the
      localization and activity of many regulatory factors. The C1 factor (HCF), a
      cellular transcription factor and coactivator, undergoes site-specific
      proteolytic processing at a series of unusual amino acid reiterations to generate
      a family of amino- and carboxyl-terminal polypeptides that remain tightly
      associated. Expression and purification of bacterially expressed domains of the
      C1 factor identifies an autocatalytic activity that is responsible for the
      specific cleavage of the reiterations. In addition, coexpression of the
      autocatalytic domain with a heterologous protein containing a target cleavage
      site demonstrates that the C1 protease may also function in trans.

PMID- 10920199
TI  - A DNA-porphyrin minor-groove complex at atomic resolution: the structural
      consequences of porphyrin ruffling.
AB  - The crystal structure of a B-type DNA hexanucleotide duplex complexed with the
      porphyrin molecule nickel-[tetra-N-methyl-pyridyl] porphyrin has been solved by
      multiwavelength anomalous diffraction phasing and refined to an R factor of 11.5%
      at a resolution of 0.9 A. The structure has been solved and refined as two
      crystallographically independent duplexes, stacked end to end. Contrary to
      expectation, the porphyrin molecule is not intercalated into the duplex but is
      stacked onto the ends of the two-duplex stack. The porphyrin molecule is highly
      buckled as a consequence of the nickel coordination, which produces large changes
      in local DNA structure. A second mode of porphyrin binding is apparent as a
      consequence of crystal packing, which places the ligand in the minor groove of an
      adjacent duplex. This structure thus provides, to our knowledge, the first atomic
      visualization of minor-groove binding for a porphyrin molecule. The geometry of
      groove binding provides a ready explanation for porphyrin-induced DNA strand
      cleavage at deoxyribose residues.

PMID- 10920197
TI  - Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship
      between H9N2 and H5N1 human isolates.
AB  - In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1
      (chicken) virus resulted in the deaths of six individuals and once again raised
      the specter of a potentially devastating influenza pandemic. Slaughter of the
      poultry in the live bird markets removed the source of infection and no further
      human cases of H5N1 infection have occurred. In March 1999, however, a new
      pandemic threat appeared when influenza A H9N2 viruses infected two children in
      Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a
      quail in Hong Kong in late 1997. Although differing in their surface
      hemagglutinin and neuraminidase components, a notable feature of these H9N2
      viruses is that the six genes encoding the internal components of the virus are
      similar to those of the 1997 H5N1 human and avian isolates. This common feature
      emphasizes the apparent propensity of avian viruses with this genetic complement
      to infect humans and highlights the potential for the emergence of a novel human
      pathogen.

PMID- 10920198
TI  - Evaluation of two-dimensional gel electrophoresis-based proteome analysis
      technology.
AB  - Proteome analysis is most commonly accomplished by a combination of two
      dimensional gel electrophoresis (2DE) to separate and visualize proteins and mass
      spectrometry (MS) for protein identification. Although this technique is
      powerful, mature, and sensitive, questions remain concerning its ability to
      characterize all of the elements of a proteome. In the current study, more than
      1,500 features were visualized by silver staining a narrow pH range (4.9-5. 7) 2D
      gel in which 0.5 mg of total soluble yeast protein was separated. Fifty spots
      migrating to a region of 4 cm(2) were subjected to MS protein identification.
      Despite the high sample load and extended electrophoretic separation, proteins
      from genes with codon bias values of <0.1 (lower abundance proteins) were not
      found, even though fully one-half of all yeast genes fall into that range.
      Proteins from genes with codon bias values of <0.1 were found, however, if
      protein amounts exceeding the capacity of 2DE were fractionated and analyzed. We
      conclude that the large range of protein expression levels limits the ability of
      the 2DE-MS approach to analyze proteins of medium to low abundance, and thus the
      potential of this technique for proteome analysis is likewise limited.

PMID- 10920200
TI  - Reelin molecules assemble together to form a large protein complex, which is
      inhibited by the function-blocking CR-50 antibody.
AB  - Reelin is a key mediator of ordered neuronal alignment in the brain. Here, we
      demonstrate that Reelin molecules assemble with each other to form a huge protein
      complex both in vitro and in vivo. The Reelin-Reelin interaction clearly is
      inhibited by the function-blocking anti-Reelin antibody, CR-50, at a
      concentration known to inhibit Reelin function. This assembly is mediated by
      electrostatic interaction of the CR-50 epitope region. Recombinant CR-50 epitope
      fragments spontaneously constitute a soluble, string-like homopolymer with a
      regularly repeated structure composed of more than 40 monomers. Mutated Reelin,
      which lacks the CR-50 epitope region, cannot form a homopolymer and fails to
      induce efficient tyrosine phosphorylation of Disabled 1 (Dab1), which should
      occur to transduce the Reelin signal. These data suggest that Reelin exerts its
      biological function by composing a large protein assembly driven by the CR-50
      epitope region, proposing a novel model of the Reelin signaling in
      neurodevelopment.

PMID- 10920202
TI  - The human VASA gene is specifically expressed in the germ cell lineage.
AB  - To understand the origins and function of the human germ cell lineage and to
      identify germ cell-specific markers we have isolated a human ortholog of the
      Drosophila gene vasa. The gene was mapped to human chromosome 5q (near the
      centromere) by radiation hybrid mapping. We show by Northern analysis of fetal
      and adult tissues that expression of the human VASA gene is restricted to the
      ovary and testis and is undetectable in somatic tissues. We generated polyclonal
      antibodies that bind to the VASA protein in formalin-fixed, paraffin-embedded
      tissue and characterized VASA protein expression in human germ cells at various
      stages of development. The VASA protein is cytoplasmic and expressed in migratory
      primordial germ cells in the region of the gonadal ridge. VASA protein is present
      in fetal and adult gonadal germ cells in both males and females and is most
      abundant in spermatocytes and mature oocytes. The gene we have isolated is thus a
      highly specific marker of germ cells and should be useful for studies of human
      germ cell determination and function.

PMID- 10920201
TI  - In vivo transposon mutagenesis of the methanogenic archaeon Methanosarcina
      acetivorans C2A using a modified version of the insect mariner-family
      transposable element Himar1.
AB  - We present here a method for in vivo transposon mutagenesis of a methanogenic
      archaeon, Methanosarcina acetivorans C2A, which because of its independence from
      host-specific factors may have broad application among many microorganisms.
      Because there are no known Methanosarcina transposons we modified the mariner
      transposable element Himar1, originally found in the insect Hematobia irritans,
      to allow its use in this organism. This element was chosen because, like other
      mariner elements, its transposition is independent of host factors, requiring
      only its cognate transposase. Modified mini-Himar1 elements were constructed that
      carry selectable markers that are functional in Methanosarcina species and that
      express the Himar1 transposase from known Methanosarcina promoters. These mini
      mariner elements transpose at high frequency in M. acetivorans to random sites in
      the genome. The presence of an Escherichia coli selectable marker and plasmid
      origin of replication within the mini-mariner elements allows facile cloning of
      these transposon insertions to identify the mutated gene. In preliminary
      experiments, we have isolated numerous mini-mariner-induced M. acetivorans
      mutants, including ones with insertions that confer resistance to toxic analogs
      and in genes that encode proteins involved in heat shock, nitrogen fixation, and
      cell-wall structures.

PMID- 10920203
TI  - Two Plasmodium falciparum genes express merozoite proteins that are related to
      Plasmodium vivax and Plasmodium yoelii adhesive proteins involved in host cell
      selection and invasion.
AB  - Two related Plasmodium falciparum genes and their encoded proteins have been
      identified by comparative analyses with Plasmodium vivax reticulocyte binding
      protein 2 (PvRBP-2). The P. falciparum genes have a structure which suggests that
      they may be the result of an evolutionary duplication event, as they share more
      than 8 kb of closely related nucleotide sequence but then have quite divergent
      unique 3' ends. Between these shared and unique regions is a complex set of
      repeats, the nature and number of which differs between the two genes, as well as
      between different P. falciparum strains. Both genes encode large hydrophilic
      proteins, which are concentrated at the invasive apical end of the merozoite and
      are predicted to be more than 350 kDa, with an N-terminal signal sequence and a
      single transmembrane domain near their C termini. Importantly, they also share
      gene structure and amino acid homology with the Plasmodium yoelii 235-kDa rhoptry
      protein family, which is also related to PvRBP-2. Together these Plasmodium
      proteins define an extended family of proteins that appear to function in
      erythrocyte selection and invasion. As such, they may prove to be essential
      components of malaria vaccine preparations.

PMID- 10920204
TI  - Cyclosporine A-induced hypertension involves synapsin in renal sensory nerve
      endings.
AB  - The calcineurin inhibitor cyclosporine A (CsA) has emerged as a major cause of
      secondary hypertension in humans, but the underlying pathogenetic mechanisms have
      remained enigmatic. Synapsins are a family of synaptic vesicle phosphoproteins
      that are essential for normal regulation of neurotransmitter release at synapses.
      In addition to synaptic vesicles, synapsins and other vesicle proteins are found
      on microvesicles in sensory nerve endings in peripheral tissues. However, the
      functions of the sensory microvesicles in general, and of synapsins in
      particular, are unknown. We now demonstrate in a mouse model that CsA raises
      blood pressure by stimulating renal sensory nerve endings that contain synapsin
      positive microvesicles. In knockout mice lacking synapsin I and II, sensory nerve
      endings are normally developed but not stimulated by CsA whereas a control
      stimulus, capsaicin, is fully active. The reflex activation of efferent
      sympathetic nerve activity and the increase in blood pressure by CsA seen in
      control are greatly attenuated in synapsin-deficient mice. These results provide
      a mechanistic explanation for CsA-induced acute hypertension and suggest that
      synapsins could serve as a drug target in this refractory condition. Furthermore,
      these data establish evidence that synapsin-containing sensory microvesicles
      perform an essential role in sensory transduction and suggest a role for synapsin
      phosphorylation in this process.

PMID- 10920205
TI  - T6BP, a TRAF6-interacting protein involved in IL-1 signaling.
AB  - We report the identification of a TRAF-interacting protein, T6BP, that
      specifically associates with TRAF6. This interaction occurs between the coiled
      coil region of T6BP and the N-terminal ring finger and zinc finger domains of
      TRAF6. IL-1, but not tumor necrosis factor, induces TRAF6-T6BP complex formation
      in a ligand-dependent manner. Formation of the TRAF6-T6BP complex depends on the
      presence of the IL-1 receptor-associated kinase (IRAK). After IL-1 stimulation,
      TRAF6 can exist in two separate complexes, TRAF6-IRAK or TRAF6-T6BP, but IRAK is
      not present in TRAF6-T6BP complexes. T6BP does not seem to play a direct role in
      activation of IkappaB kinases or Jun N-terminal kinase.

PMID- 10920206
TI  - Purified hematopoietic stem cell grafts induce tolerance to alloantigens and can
      mediate positive and negative T cell selection.
AB  - Engraftment of allogeneic bone marrow (BM) has been shown to induce tolerance to
      organs genotypically matched with the BM donor. Immune reconstitution after BM
      transplantation therefore involves re-establishment of a T cell pool tolerant to
      antigens present on both donor and host tissues. However, how hematopoietic
      grafts exert their influence over the regenerating immune system is not
      completely understood. Prior studies suggest that education of the newly arising
      T cell pool involves distinct contributions from donor and host stromal elements.
      Specifically, negative selection is thought to be mediated primarily by donor BM
      derived antigen-presenting cells, whereas positive selection is dictated by radio
      resistant host-derived thymic stromal cells. In this report we studied the effect
      of highly purified allogeneic hematopoietic stem cells (HSCs) on organ
      transplantation tolerance induction and immune reconstitution. In contrast to
      engraftment of BM that results in near-complete donor T cell chimerism, HSC
      engraftment results in mixed T cell chimerism. Nonetheless we observed that HSC
      grafts induce tolerance to donor-matched neonatal heart grafts, and one way the
      HSC grafts alter host immune responses is via deletion of newly arising donor as
      well as radiation-resistant host T cells. Furthermore, using an in vivo assay of
      graft rejection to study positive selection we made the unexpected observation
      that T cells in chimeric mice rejected grafts only in the context of the donor
      MHC type. These latter findings conflict with the conventionally held view that
      radio-resistant host elements primarily dictate positive selection.

PMID- 10920207
TI  - Bacterial and yeast chaperones reduce both aggregate formation and cell death in
      mammalian cell models of Huntington's disease.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative condition
      caused by expansions of more than 35 uninterrupted CAG repeats in exon 1 of the
      huntingtin gene. The CAG repeats in HD and the other seven known diseases caused
      by CAG codon expansions are translated into long polyglutamine tracts that confer
      a deleterious gain of function on the mutant proteins. Intraneuronal inclusions
      comprising aggregates of the relevant mutant proteins are found in the brains of
      patients with HD and related diseases. It is crucial to determine whether the
      formation of inclusions is directly pathogenic, because a number of studies have
      suggested that aggregates may be epiphenomena or even protective. Here, we show
      that fragments of the bacterial chaperone GroEL and the full-length yeast heat
      shock protein Hsp104 reduce both aggregate formation and cell death in mammalian
      cell models of HD, consistent with a causal link between aggregation and
      pathology.

PMID- 10920208
TI  - A distinctive role for the Yersinia protein kinase: actin binding, kinase
      activation, and cytoskeleton disruption.
AB  - The bacterial pathogens of the genus Yersinia deliver several virulence factors
      into target cells using a type III secretion system. We demonstrate that Yersinia
      protein kinase A (YpkA), an essential bacterial virulence factor, is produced as
      an inactive serine/threonine kinase. The inactive kinase is activated within the
      host cell by a cytosolic eukaryotic activator. Using biochemical purification
      techniques, we demonstrate that actin is a cellular activator of YpkA. This
      stimulation of YpkA kinase activity by actin depends on the presence of the C
      terminal twenty amino acids of YpkA, because deletion of these 20 aa not only
      obliterates YpkA activity, but it also destroys the interaction between YpkA and
      actin. Activated YpkA functions within cultured epithelial cells to disrupt the
      actin cytoskeleton. The disruption of the actin cytoskeleton by YpkA would be
      expected to inhibit macrophage function and phagocytosis of Yersinia.

PMID- 10920209
TI  - Molecular mechanism of endothelial growth arrest by laminar shear stress.
AB  - This study was designed to elucidate the mechanism underlying the inhibition of
      endothelial cell growth by laminar shear stress. Tumor suppressor gene p53 was
      increased in bovine aortic endothelial cells subjected to 24 h of laminar shear
      stress at 3 dynes (1 dyne = 10 microN)/cm(2) or higher, but not at 1.5
      dynes/cm(2). One of the mechanisms of the shear-induced increase in p53 is its
      stabilization after phosphorylation by c-Jun N-terminal kinase. To investigate
      the consequence of the shear-induced p53 response, we found that prolonged
      laminar shear stress caused increases of the growth arrest proteins GADD45
      (growth arrest and DNA damage inducible protein 45) and p21(cip1), as well as a
      decrease in phosphorylation of the retinoblastoma gene product. Our results
      suggest that prolonged laminar shear stress causes a sustained p53 activation,
      which induces the up-regulation of GADD45 and p21(cip1). The resulting inhibition
      of cyclin-dependent kinase and hypophosphorylation of retinoblastoma protein lead
      to endothelial cell cycle arrest. This inhibition of endothelial cell
      proliferation by laminar shear stress may serve an important homeostatic function
      by preventing atherogenesis in the straight part of the arterial tree that is
      constantly subjected to high levels of laminar shearing.

PMID- 10920210
TI  - GIGANTEA is a nuclear protein involved in phytochrome signaling in Arabidopsis.
AB  - In a genetic screen of available T-DNA-mutagenized Arabidopsis populations for
      loci potentially involved in phytochrome (phy) signaling, we identified a mutant
      that displayed reduced seedling deetiolation under continuous red light, but
      little if any change in responsiveness to continuous far-red light. This behavior
      suggests disruption of phyB, but not phyA signaling. We have cloned the mutant
      locus by using the T-DNA insertion and found that the disrupted gene is identical
      to the recently described GIGANTEA (GI) gene identified as being involved in
      control of flowering time. The encoded GI polypeptide has no sequence similarity
      to any known proteins in the database. However, by using beta-glucuronidase-GI
      and green fluorescent protein-GI fusion constructs, we have shown that GI is
      constitutively targeted to the nucleus in transient transfection assays. Optical
      sectioning by using the green fluorescent protein-GI fusion protein showed green
      fluorescence throughout the nucleoplasm. Thus, contrary to previous computer
      based predictions that GI would be an integral plasma membrane-localized
      polypeptide, the data here indicate that it is a nucleoplasmically localized
      protein. This result is consistent with the proposed role in phyB signaling,
      given recent evidence that early phy signaling events are nuclear localized.

PMID- 10920211
TI  - Calcium kinetics in children with osteogenesis imperfecta type III and IV: pre-
      and post-growth hormone therapy.
AB  - Children with osteogenesis imperfecta (OI) type III and type IV were studied
      using a (42)Ca stable isotope technique. Serum dilution kinetics of (42)Ca were
      studied pre- and post-growth hormone (GH) treatment in 9 OI III (age range 5-9
      years) and 8 OI IV patients (age range 5-12 years). Each subject was studied
      twice: at baseline and following GH therapy (range 1-1.5 years). Isotopic
      enrichments of (42)Ca were followed over 7 days using thermal ionization mass
      spectrometry. A binding site model, which describes reversible and irreversible
      binding of calcium (Ca) ions to postulated short- and long-term binding sites in
      bone, was used to analyze the kinetic data. In type III patients, GH treatment
      (1) increased the fraction of short-term binding sites, theta (0.777 +/- 0.112
      versus 0.877 +/- 0.05, respectively; P = 0.034); (2) increased the apparent half
      life of a Ca ion attached to the long-term binding site by 76% (P = 0. 009); (3)
      although not statistically significant (P = 0.098), a trend toward an increased
      growth rate was observed with increasing change in theta (Deltatheta); (4)
      patients experienced a 75% increase in growth rate during the first 6 months of
      treatment. In type IV patients, GH treatment increased the apparent half-life of
      a Ca ion attached to the long-term binding site by 83% (P = 0.048), however, no
      trend toward an increased growth rate was observed with increasing Deltatheta in
      these patients. These significant changes in Ca binding to bone may influence
      growth in type III patients.

PMID- 10920212
TI  - Normal values for tibial quantitative ultrasonometry in caucasian children and
      adolescents (aged 6 to 19 years).
AB  - Bone densitometry in children is a relatively new topic of interest within the
      field of osteoporosis. Bone densitometry techniques using an X-ray source have
      the disadvantage of radiation exposure. Also on some systems, motion artifacts
      are caused by long scan times. Tibial quantitative ultrasonometry (QUS) is
      ideally suited for children as it is radiation free and the interactive
      measurement provides real-time quality control. In this prospective study, we
      present data from 596 healthy children-309 girls, mean age 12.9 years (range 6.1
      19.9), and 287 boys, mean age 12.3 years (range 6.1-19.6) from Rotterdam, The
      Netherlands. For all subjects, a short questionnaire regarding overall health was
      completed. To assess skeletal age, an X-ray of the left hand was taken and tibial
      QUS of the right tibia was performed using the SoundScan Compact. A statistically
      significant correlation was found between age and speed of sound (SOS)-r(2)(boys)
      = 0.52 and r(2)(girls) = 0.63 (both P < 0.001) and between skeletal age and SOS
      r(2)(boys) = 0.56 and r(2)(girls) = 0. 63 (both P < 0.001). In boys, significant
      increase of mean SOS is seen between Tanner stages II and III and between IV and
      V. In girls there is a significant increase of mean SOS among all Tanner stages,
      except stages II and III. This is the first study to present normative tibial QUS
      data for Caucasian children and adolescents. In this study, normative data
      relative to skeletal age are also provided, facilitating the implementation of
      this technique in children with growth disorders showing dissociation between
      calendar and skeletal age.

PMID- 10920213
TI  - Calcaneus bone mineral density is lower among men and women with lower physical
      performance.
AB  - Fracture risk is influenced by both bone strength and by falls. Measures of
      physical function and performance are predictors of falls. However, the
      interrelationships among bone mineral density (BMD), regular physical activity,
      and measures of physical performance are not well known. We studied 447 community
      dwelling Japanese people aged 40 years and over (96 men and 351 women) to examine
      the association of calcaneus BMD with measures of physical performance (grip
      strength, walking speed, chair stand, and functional reach) and regular physical
      activity. Calcaneus BMD decreased with age by approximately 25% in men and 42% in
      women. Measures of physical performance decreased with age by approximately 30%
      in both genders, however, performance on the chair stand test declined by
      approximately 60%. There were only minimal differences in performance measures
      and calcaneus BMD between people with and those without regular physical activity
      in both genders, and most differences were not significant. However, there were
      significant BMD increases of 3-6% per standard deviation (SD) increase in all
      performance measures for women and a 7% increase in BMD per SD increase in grip
      strength for men, after adjusting for age. These associations remained after
      additional adjustment for body mass index and regular physical activity. These
      findings suggest that bone density and physical function decline markedly in both
      men and women with age, and that low BMD and poor function tend to occur
      together, which would increase fracture risk more than either risk factor alone.

PMID- 10920214
TI  - Total body and regional bone mineral densitometry (BMD) and soft tissue
      measurements: correlations of BMD parameter to lumbar spine and hip.
AB  - Bone loss in men and women seems to differ according to the skeletal regions or
      particular areas being evaluated. Dual energy X-ray absorptiometry (DXA) is the
      method of choice for measuring total body and regional bone mineral area density
      (BMD). The aim of the study was to evaluate the importance of DXA measurements of
      total body in relation to lumbar spine and hip in different scan beam designs. In
      300 patients, ages 43-80 years, lumbar spine, hip, total body and regional bone
      mineral area density, and soft tissue measurements were performed on all subjects
      in the supine position on a QDR 2000 using single beam (SB) and fan beam (FB).
      Short-term precision errors were 0.7% (SB) and 1.2% (FB) for BMD total of the
      total body and between 1.2% and 8.0% for soft tissue measurements. All mid-term
      precision errors of BMD total, right and left leg, and pelvis were below 2.0%
      with SB and FB, whereas precision errors of thoracic and lumbar spine varied
      depending on the scan mode being applied. In contrast, all mid-term precision
      errors of soft tissue measurements were greater (2.6-11.0%). All SB values of BMD
      and soft tissue measurement were significantly higher than FB values, except for
      BMD values of the head, thoracic spine, and pelvis. Furthermore, BMD total of the
      total body scan correlated significantly (P < 0. 001) with all subregional
      parameters with best "r"-values (0.86-0. 92) for the right and left leg in SB and
      FB design. In addition, there were excellent correlations (r > 0.94, P < 0.001)
      between the right and left legs (SB and FB) or arms (SB). There were also highly
      significant correlations between the lumbar spine (or hip) and total body, being
      best for the subregional thorax. Our data demonstrate short-and mid-term
      precision errors of BMD with reproducible results for most areas in SB and FB
      design, whereas soft tissue measurements vary depending on the area being
      measured. Furthermore, there is a close relationship between BMD values of total
      body total and subregional parameters and lumbar spine and hip scans,
      respectively.

PMID- 10920215
TI  - Prevention of osteoporosis in heart transplant recipients: a comparison of
      calcitriol with calcitonin and pamidronate.
AB  - Bone loss and osteoporotic fractures are common in cardiac transplant recipients.
      To compare two prophylactic medical regimens after heart transplantation, 26
      consecutive heart transplant recipients were randomized to receive either
      continuous oral calcitriol (0.5 microg/day) combined with nasal salmon calcitonin
      (200 U/day) for the first 3 months (group A) or intermittent intravenous
      pamidronate (0.5 mg/kg body weight) every third month (group B). Bone mineral
      density (BMD) and biochemical indices of bone turnover were measured at baseline
      and 3, 6, 12, and 18 months after transplantation. The mean pretransplant BMD,
      measured by dual energy X-ray absorptiometry (DXA) was significantly lower in the
      patients compared with age-matched healthy controls. During the first year of
      treatment, rates of bone loss at the lumbar spine and femoral neck were slightly
      but significantly slower in the patients treated with pamidronate, but there was
      no longer a significant difference between the two groups after 18 months of
      heart transplantation. Irrespective of the mode of osteoporosis prevention,
      osteocalcin levels increased whereas urinary deoxypyridinoline decreased after
      transplantation, and significant bone loss was observed in both treatment groups.
      We found no relationship between initial BMD, markers of bone turnover,
      cumulative glucocorticoid dose, or cyclosporine levels and the rate of bone loss
      after cardiac transplantation. In summary, we found that the rapid and severe
      bone loss following heart transplantation could be attenuated by two preventive
      measures, pamidronate or calcitriol with calcitonin.

PMID- 10920216
TI  - Bone mass and markers of bone and calcium metabolism in postmenopausal women
      treated with 1,25-dihydroxyvitamin D (Calcitriol) for four years.
AB  - To evaluate the long-term effect of calcitriol treatment on bone mineral density
      (BMD) of the femoral neck and lumbar spine and the parameters of calcium and bone
      metabolism in elderly women, 55 healthy, postmenopausal women, all aged 66 years,
      were enrolled in the study. Eighteen started a 4-year supplementation with 0.5
      microg of calcitriol daily and 37 served as controls. Calcium intake of all the
      subjects was adjusted to 800 mg daily. In 4 years femoral neck BMD increased by
      3.0% in the calcitriol group, but decreased by 1.6% in the control group (P =
      0.009). The respective changes in lumbar spine BMD were +2.3% and +0.9% (P =
      0.067). Two years' treatment with calcitriol increased the intestinal absorption
      of strontium by 57% (P < 0.001), doubled the urinary excretion of calcium (P < 0.
      001), and decreased the mean parathyroid hormone (PTH) level by 32% (P < 0.01).
      In the calcitriol group the marker of bone formation, serum osteocalcin,
      decreased by 27% (P < 0.01), and the marker of bone resorption, serum C
      telopeptide of type I collagen (CTx), by 33% (P = 0.05) after 2 years. In two
      subjects the calcitriol dose had to be reduced because of hypercalciuria. We
      conclude that calcitriol treatment increases bone mass at the femoral neck and
      lumbar spine, the increases being maintained for up to 4 years. The gain in bone
      mass results from reduced bone turnover which is partly a consequence of the
      enhanced intestinal absorption of calcium and suppressed serum PTH levels.

PMID- 10920217
TI  - Microstructural analysis of severe bone lesions in seven thalassemic patients
      treated with deferoxamine.
AB  - Osteochondrodystrophic lesions, mainly affecting long bone metaphyses, can be
      radiologically evident in homozygotic thalassemic patients treated with
      deferoxamine, and their incidence rate varies among authors. The clinical and
      radiological appearance of these lesions is described in the literature, but
      microstructural data are still lacking. The aim of our research was to evaluate
      the microstructure of five tibial biopsy specimens from thalassemic patients with
      bone lesions (5 cases out of 180 patients followed for the last 10 years, i.e.,
      2.8%) and two bone biopsy specimens from thalassemic patients with no
      radiological alteration of the long bones. As control, bone tissue taken from
      autoptic tibiae of two subjects with no skeletal pathology was used. Using
      microradiography and X-ray diffraction (XRD), we found a reduced and irregular
      mineralization of the bone (compared with controls) in thalassemic subjects. Bone
      tissue microhardness was also significantly reduced. Nevertheless, bone apatite
      lattice was unaltered and no 'foreign' crystallographic phase was recorded by
      XRD. In conclusion, all the patients shared a similar picture of abnormal bone,
      even with no radiological evidence of lesion.

PMID- 10920218
TI  - Osteochondrodystrophic lesions in chelated thalassemic patients: an histological
      analysis.
AB  - Some patients affected by thalassemia major and treated with an iron-chelating
      drug such as deferioxamine can suffer from severe osteochondrodystrophic lesions
      of the long bones. These lesions were radiologically and clinically evident in
      2.8% of the patients we examined over the last 10 years. The aim of our research
      was to evaluate the morphology and morphometry of five tibial biopsy specimens
      taken from thalassemic patients with bone lesions and two bone biopsy specimens
      taken from thalassemic patients with no alteration of the long bones. All the
      bone samples showed a similar morphostructure. Abnormal chondrocytes, alteration
      of cartilage staining pattern, irregular columnar cartilage, and lacunae in the
      cartilaginous tissue were revealed histologically. Osteoid thickness was either
      normal or slightly increased. Some bone trabeculae had microfractures and some
      had cartilagineous oases. In five cases, iron deposition was detectable by Perls'
      Prussian Blue staining. It can be concluded that even in patients without
      radiographic signs of lesions, seriously damaged columnar cartilage, altered bone
      mineralization, and microfractures are common.

PMID- 10920219
TI  - Down-regulation of osteoblastic cell differentiation by epidermal growth factor
      receptor.
AB  - The role of epidermal growth factor receptors (EGF-R) in osteogenic cell
      differentiation was investigated using preosteoblastic MC3T3-E1 (MC3T3) cells and
      osteoblast-like ROS 17/2.8 (ROS) cells. When cultured in the presence of beta
      glycerophosphate (GP) and ascorbic acid (AA), MC3T3 cells underwent spontaneous
      differentiation into osteoblasts which was confirmed as they expressed osteoblast
      markers such as alkaline phosphatase (ALP), bone sialoprotein (BSP) and
      osteocalcin (OC). Interestingly, the number of EGF-binding sites decreased during
      their differentiation into osteoblasts, and the osteogenic protein-1 (OP-1)
      treatment, which accelerated their differentiation, lowered the number of EGF
      binding sites even further. On the other hand, ROS cells with high expression
      levels of osteoblast markers and no EGF-R, after being transfected with human EGF
      R cDNA (EROS cells), expressed numerous EGF-binding sites as well as EGF-R mRNA
      and protein; in the process, they ceased to express osteoblast markers,
      indicating their dedifferentiation into osteoprogenitor cells. Both MC3T3 and
      EROS cells showed increased cell growth in response to EGF, whereas ROS cells did
      not. These results imply that the EGF/EGF-R system in osteogenic cells has a
      crucial function in osteoblast phenotype suppression and osteogenic cell
      proliferation.

PMID- 10920220
TI  - Induction of interleukin-6 release in human osteoblast-like cells exposed to
      titanium particles in vitro.
AB  - Orthopaedic wear debris induces release of bone-resorbing factors from
      macrophages and fibroblasts. However, the extent to which elemental metallic
      particles induce bone cells to express factors contributing to implant loosening
      remains unclear. This study showed that exposure of MG-63 osteoblast-like cells
      to titanium particles at a concentration of 0.30% v/v resulted in a 15-fold
      increase in IL-6 release into the culture medium after 24 hours, when compared
      with cells without particles. Northern blots revealed that exposure of MG-63
      cells to titanium particles at a concentration of 0.30% v/v for 24 hours
      increased IL-6 mRNA signal levels by 9.6-fold, when compared with control
      cultures. Pretreatment of MG-63 cells with cytochalasin B prevented the particle
      induced increase of IL-6 expression but did not alter the basal level of IL-6
      release from cells cultured in the absence of particles. The protein kinase C
      inhibitor, H7, and the serine/threonine kinase inhibitor, genistein, abolished
      the particle-induced increase in IL-6 release at a concentration of 100 microM
      for each compound. In contrast, an inhibitor of protein kinase A, HA1004, had no
      effect on the particle-induced increase in IL-6 release. The transcription
      factors, nuclear factor IL-6 and nuclear factor kappa B, translocated into the
      nucleus within 1 hour of particle exposure. This study showed that osteoblast
      like cells respond to titanium particles through increased expression of the
      proinflammatory cytokine, IL-6, in a process requiring phagocytosis and
      intracellular signaling pathways. These results suggest that osteoblasts play a
      direct role in implant loosening because of localized release of soluble
      mediators such as interleukin-6.

PMID- 10920221
TI  - A morphometric evaluation of allograft matrix combinations in the treatment of
      osseous defects in a baboon model.
AB  - Recent and ongoing research efforts have been made to increase the efficacy of
      biomaterials as structural fillers during in vivo bony reconstructions. Although
      the selection of the possible material choices has grown, a biomaterial that can
      be physically molded to the defect/void space as well as offer biomimetic tissue
      regeneration has yet to be made available. With the potential success of
      demineralized freeze-dried bone allografts (DFDBA) combined with tendonous
      collagen as an effective filling material, further research should help to
      elucidate its use. The purpose of this study was to evaluate the regenerative
      healing response of five allograft mixtures via the morphology of filled,
      periodontal defects. Critical size mandibular and maxillary osseous defects were
      surgically created in six adult baboons. The filling response of four
      combinations of DFDBA and tendon collagen was compared with an all-collagen graft
      after 3 months of implantation. The overall results indicate that all
      combinations of DFDBA and collagen provided a better fill response than the all
      collagen matrix (P < 0. 05). Statistically, however, all of the combinations were
      similar (P > 0.05) with a 60:40 collagen to DFDBA mass ratio resulting in the
      largest defect fill response.

PMID- 10920222
TI  - Mechanical loading stimulates differentiation of periodontal osteoblasts in a
      mouse osteoinduction model: effect on type I collagen and alkaline phosphatase
      genes.
AB  - The effects of mechanical loading on the osteoblast phenotype remain unclear
      because of many variables inherent to the current experimental models. This study
      reports on utilization of a mouse tooth movement model and a semiquantitative
      video image analysis of in situ hybridization to determine the effect of
      mechanical loading on cell-specific expression of type I collagen (collagen I)
      and alkaline phosphatase (ALP) genes in periodontal osteoblasts, using nonosseous
      cells as an internal standard. The histomorphometric analysis showed intense
      osteoid deposition after 3 days of treatment, confirming the osteoinductive
      nature of the mechanical signal. The results of in situ hybridization showed that
      in control periodontal sites both collagen I and ALP mRNAs were expressed
      uniformly across the periodontium. Treatment for 24 hours enhanced the ALP mRNA
      level about twofold over controls and maintained that level of stimulation after
      6 days. In contrast, collagen I mRNA level was not affected after 24 hours of
      treatment, but it was stimulated 2.8-fold at day 6. This increase reflected
      enhanced gene expression in individual osteoblasts, since the increase in
      osteoblast number was small. These results indicate that (1) the mouse model and
      a semiquantitative video image analysis are suitable for detecting osteoblast
      specific gene regulation by mechanical loading; (2) osteogenic mechanical stress
      induces deposition of bone matrix primarily by stimulating differentiation of
      osteoblasts, and, to a lesser extent, by an increase in number of these cells;
      (3) ALP is an early marker of mechanically-induced differentiation of
      osteoblasts. (4) osteogenic mechanical stimulation in vivo produces a cell
      specific 2.8-fold increase in collagen gene expression in mature, matrix
      depositing osteoblasts located on the bone surface and within the osteoid layer.

PMID- 10920223
TI  - Differences in bone turnover and skeletal response to thyroid hormone treatment
      between estrogen-depleted and repleted rats.
AB  - This study was undertaken to compare the effect of supraphysiological doses of
      thyroxine (T4) on bone metabolism in SHAM and OVX young adult rats. Female
      Sprague Dawley rats (220 +/- 2 g, approx. 5 months of age) were divided into four
      groups of eight animals each. The animals were intraperitoneally injected 6 days
      per week with vehicle (Vh): 0.001 N NaOH/0.9% NaCl (SHAM+Vh and OVX+Vh) or 250
      microg of thyroxine/kg/day (SHAM+T4 and OVX+T4) during a 5-week period. Serum T4
      and osteocalcin (BGP), urinary pyridinolines (Pyr), and creatinine (creat) were
      determined. At the beginning and at end of the experiment, skeletal bone mineral
      content (BMC), bone mineral density (BMD), and area (A) of the total skeleton,
      femur, spine, and whole tibia, as well as proximal, middle, and distal areas of
      the tibia were assessed by dual X-ray absorptiometry (DXA) in an ultra-high
      resolution mode. T4 treatment of the SHAM rats did not induce significant changes
      in BGP level or Pyr/creat excretion compared with the SHAM+Vh control group.
      However, these two biochemical bone markers significantly increased due to T4
      treatment in OVX rats compared with both OVX+Vh and SHAM+T4 groups (P < 0.05 and
      P < 0.001, respectively). The OVX+T4 group had a significantly lower DeltaBMD
      than SHAM+T4 rats in all studied regions (P < 0.05) except for the middle tibia
      region. OVX+T4 groups presented a significantly lower DeltaBMC and DeltaA
      compared with SHAM+T4 animals (P < 0.001). OVX+T4 rats significantly impaired the
      DeltaBMD in the femur (P < 0.01), spine (P < 0.05), whole (P < 0.05) and middle
      (P < 0.05) tibia whereas T4 treatment of SHAM rats only affected, significantly,
      the whole (P < 0.05) and the proximal tibia region (P < 0.01). T4 treatment
      affects bone growth in young adult rats. The effect is significantly greater in
      the estrogen-depleted than in the estrogen-repleted state. The bone site most
      adversely affected by T4 treatment depends on the estrogen status. The proximal
      tibia (principally trabecular bone) was the most affected area in estrogen
      repleted rats. Conversely, in OVX rats, the middle tibia (principally cortical
      bone) presented the greatest decrease in bone density.

PMID- 10920226
TI  - European calcified tissue society

PMID- 10920225
TI  - Toward a mathematical description of bone biology: the principle of cellular
      accommodation.

PMID- 10920224
TI  - Acid pH increases carbonic anhydrase II and calcitonin receptor mRNA expression
      in mature osteoclasts.
AB  - Numerous resorptive stimuli have been shown to enhance osteoclast
      differentiation, increasing osteoclast numbers and accelerating bone resorption.
      Currently, there is much less understanding of regulation of mature osteoclast
      activity. Indeed, there is presently only minimal evidence of changes in gene
      expression as a mechanism for altering bone resorption. We investigate here, in
      the mature osteoclast, regulation of 2 genes-carbonic anhydrase II (CAII) and
      calcitonin receptor (CTR) in response to acidosis, which is known to increase
      bone resorption. We studied the effect of acid pH on CAII and CTR mRNA expression
      in mature osteoclasts raised in coculture of ST-2 and primary marrow cells. On
      day 6 of culture, stromal cells were removed with collagenase, the remaining
      osteoclasts were incubated overnight, and then exposed to varying pH. RT-PCR was
      performed on total RNA using primers for CAII, CTR, or glyceraldehyde
      dehydrogenase phosphate (GAP). Expression of CTR mRNA was increased 2.14 +/- 0.41
      and 2.56 +/- 0.45 (P < 0.05)-fold by a 4-hour exposure to pH 6.75 and 6.5,
      respectively. CAII mRNA was similarly increased 2.18 +/- 0.42 and 2.63 +/- 0.48
      (P < 0.05)-fold by pH 6.75 and 6.5, respectively. Increased expression of CAII
      and CTR mRNA was seen by 2 hours and maximally by 4 hours. Increased expression
      of CTR and CAII mRNA was not explained by increases in osteoclast numbers: pH 7.4
      100 +/- 3.7, 6.75-133 +/- 8.3, 6.5-124 +/- 7.8. These results demonstrate
      upregulation of two osteoclast genes in response to acidosis, illustrating the
      ability of the mature osteoclast to respond to resorptive signals with increased
      functional gene expression.

PMID- 10920227
TI  - Applications of DNA microarrays to the transcriptional analysis of mammalian
      genomes.

PMID- 10920228
TI  - Genomic organization, chromosomal assignment, and expression analysis of the
      mouse suppressor of fused gene (Sufu) coding a Gli protein partner.
AB  - Suppressor of fused (Sufu) is a negative regulator of the Hedgehog pathway both
      in Drosophila and vertebrates. Here, we report the genomic organization of the
      mouse Sufu gene (mSufu). This gene comprises 11 exons spanning more than 30 kb
      and encodes a protein with a putative PEST sequence. DNA-consensus sequences
      recognized by basic helix-loop-helix (bHLH) proteins, referred to as E-box
      motifs, are found in the 5' flanking region. Analysis by single-strand
      conformation polymorphism and radiation hybrid positioned the Sufu locus to the
      distal end of mouse Chr 19 between D19Mit102 and D19Mit9, near the Fgf8 and
      dactylin genes. Mouse Sufu is expressed in various tissues, particularly in the
      nervous system, ectoderm, and limbs, throughout the developing embryo. Sufu binds
      with all three Gli proteins, with different affinities. This report, in
      conjunction with recent studies, points out the importance of Sufu in mouse
      embryonic development.

PMID- 10920229
TI  - Identification of the promoter, genomic structure, and mouse ortholog of LGI1.
AB  - The human LGI1 gene is a leucine-rich, repeat-containing gene that was cloned
      from the t(10:19) breakpoint of the T98G glioblastoma cell line. The LGI1 gene
      maps to 10q24, a region of peak LOH in malignant gliomas, and is inactivated
      during the transition from low to high-grade brain tumors. Here we report
      detailed studies of the genomic structure of the LGI1 gene and its promoter. We
      have also cloned and characterized the mouse lgil gene, which is 97% homologous
      to the human gene at the amino acid level and 91% homologous at the nucleotide
      level. LGI1 contains 8 exons, where each of the four leucine-rich repeat units is
      contained in an individual 72-bp exon. The cysteine-rich regions flanking the LRR
      and the single trans-membrane domain do not occupy individual exons.
      Approximately 5-kb of the genomic region 5' to LGI1 was sequenced, but
      conventional CAAT and TATA motifs were not present within this sequence. A 597-bp
      fragment of this 5' sequence was cloned upstream of a promoterless luciferase
      gene and was shown to be sufficient to drive transcription. SSCP analysis of the
      coding region of LGI1 in 20 glioblastomas and five cell lines did not reveal any
      mutations. Because LGI1 expression is considerably downregulated in gliomas, we
      also investigated whether this was owing to changes in the methylation status of
      the promoter. Southern blot analysis and 5-azacytidine treatment did not show any
      appreciable difference in methylation status between normal brain and
      glioblastomas.

PMID- 10920230
TI  - Molecular cloning and functional characterization of murine transmembrane
      activator and CAML interactor (TACI) with chromosomal localization in human and
      mouse.
AB  - The human Taci gene (Transmembrane Activator and CAML Interactor) encodes a
      recently discovered member of the Tumor Necrosis Factor Receptor family. TACI is
      expressed in B-lymphocytes and may act to regulate humoral immunity. To identify
      functionally important regions of the protein, we have isolated and characterized
      the murine homolog of the human Taci cDNA. The proteins display 61.5% similarity
      and 54.6% identity. Mouse TACI is a type III transmembrane protein, as judged by
      the lack of a cleaved signal sequence and its N-terminal extracellular exposure.
      The intracellular domains of the mouse and human proteins share a single, defined
      region of high sequence conservation (19 of 23 residues identical). This
      constitutes a novel domain that may play a part in the initiation of signal
      transduction through TACI. In support of this notion, mouse TACI was found to
      activate NFAT, NFkB, and AP1 transcription factors in a transient transfection
      assay. The Taci gene was localized to human Chromosome (Chr) 17p11 by
      fluorescence in situ hybridization. The murine homolog was localized by
      intraspecific backcross analysis to the middle of Chr 11, a region that is
      syntenic to human Chr 17p. This work identifies conserved domains within TACI
      that may mediate the cellular distribution and signal transduction function of
      the protein and extend the details of homology between mouse Chr 11 and human
      17p.

PMID- 10920231
TI  - Transcription mapping and expression analysis of candidate genes in the vicinity
      of the mouse Loop-tail mutation.
AB  - Loop-tail (Lp) is a semidominant mutation that maps to the distal portion of
      mouse Chromosome (Chr) 1 and is an established model for neural tube defects
      (NTDs). Homozygous embryos exhibit an open neural tube from the caudal midbrain
      to the tip of the tail that results from over-differentiation of the floor plate.
      To facilitate the positional cloning of the Lp gene, both cDNA selection and
      assignment of sequence-tagged-sites from the human transcript map have been used
      to identify genes within the Lp interval. Together with previous physical
      mapping, this has allowed the placement of 13 transcription units within an
      approximately 1-Mb region that spans the Lp genetic interval, and eight of these
      genes map to the nonrecombinant interval. This map includes genes that encode
      proteins involved in protein sorting and targeting (Tim23 and Copa), ion
      transport (Atp1a2, Atp1a4, and Girk3), transcription (Nhlh1), immune regulation
      (Cd48 and Fcer1alpha), cell adhesion (R88252), apoptosis (Pea15), and several of
      unknown function (H326, Kiaa0253, and Estm34). Expression analysis by Northern
      blotting indicated that a subset of these genes are expressed preferentially in
      the developing nervous system. Finally, this region of mouse Chr 1 represents a
      conserved linkage group with genes on human chromosome 1q21, a region that is
      frequently altered in human cancers and that harbors loci for several genetic
      conditions. Consequently, analysis of the Lp interval may provide important tools
      to understand how the corresponding region of human Chr 1 contributes to disease,
      in addition to defining a key gene product required for neurulation.

PMID- 10920232
TI  - Quantitative trait loci that modify the sootiness of yellow pigmentation in KK
      A(y)/a mice.
AB  - Compared with C57BL/6J-A(y)/a, KK-A(y)/a mice have yellow fur that is markedly
      darker. Furthermore, there is a considerable variation in the tone of color with
      a continuous range in F(2) progeny produced from C57BL/6J females and KK-A(y)/a
      males. The aims of this study are to reveal the phenotypic differences between
      the two A(y) congenic strains and to elucidate the genetic factors responsible
      for the sooty yellow pigmentation in the KK background. On the basis of a
      chemical analysis, the sootiness in KK-A(y)/a was the result of increased
      eumelanin (PTCA) and decreased pheomelanin (AHP). A statistically significant QTL
      was identified on Chromosome (Chr) 15, responsible for the AHP content. No
      significant loci responsible for PTCA were identified. On the other hand, on the
      basis of an optical analysis for color difference and overall sootiness,
      significant evidence of linkage was identified on the proximal part of Chr 15, in
      the region similar to AHP QTL. The overall sootiness is thus controlled solely by
      the locus on Chr 15 in F(2) progeny; however, the KK allele at this locus
      significantly increased the AHP content.

PMID- 10920233
TI  - Fine mapping of trypanosomiasis resistance loci in murine advanced intercross
      lines.
AB  - We have previously reported the results of genome-wide searches in two murine
      F(2) populations for QTLs that influence survival following Trypanosoma
      congolense infection. Three loci, Tir1, Tir2, and Tir3, were identified and
      mapped to mouse Chromosomes (Chrs) 17, 5, and 1 respectively, with confidence
      intervals (CIs) in the range 10-40 cM. The size of these CIs is to a large degree
      the consequence of limited numbers of recombination events in small chromosomal
      regions in F(2) populations. A number of population designs have been proposed to
      increase recombination levels in crosses, one of which is the advanced intercross
      line (AIL). Here we report fine mapping of Tir1, Tir2, and Tir3 in G6 populations
      of two independent murine AILs created by crossing the C57BL/6J strain with the
      A/J and BALB/cJ strains, respectively. Data were analyzed by two methods that
      gave equally informative and similar results. The three QTLs were confirmed in
      the A/J x C57BL/6J AIL and in the combined data set, but Tir2 was apparently lost
      from the BALB/cJ x C57BL/6J AIL. The reduction in CIs for the Tir loci ranged
      from 2.5 to more than ten-fold in G6 populations by comparison with CIs obtained
      previously in the equivalent F(2) generations. Mapping in the AILs also resolved
      the Tir3 locus into three trypanosomiasis resistance QTLs, revealing a degree of
      complexity not evident in extensive studies at the F(2) level.

PMID- 10920234
TI  - Identification of a novel myosin-Va mutation in an ataxic mutant rat, dilute
      opisthotonus.
AB  - Mutations of the myosin-Va gene (Myo5a) cause diluted coat color in mice and are
      occasionally associated with severe neurological disorders. Dilute-opisthotonus
      (dop) is a spontaneous gene mutation in the rat, and phenotypes of the homozygote
      (dop/dop) are similar to those of the Myo5a-deficient mouse, suggesting that the
      mutation resides in the rat Myo5a gene. To elucidate the molecular basis of the
      dop mutation, we cloned the rat Myo5a cDNA from the wild type and the dop/dop.
      The wild-type rat Myo5a cDNA contained a 5487-bp ORF and showed higher homology
      with Myo5a of the other species than Myr6 (Myo5b) in the rat. A 141-bp in-frame
      deletion was detected in the head region in the dop cDNA. An intragenic
      rearrangement consisting of a 306-bp inversion associated with 17-bp and 217-bp
      deletions were identified in the Myo5a gene of the dop genome. This rearrangement
      involved a 141-bp exon, which was skipped in the dop transcript. The MyoVA
      protein expression was severely impaired in the dop/dop brain. This is the first
      report to define the dop mutation as the Myo5a gene abnormality in the rat.

PMID- 10920235
TI  - Fine mapping and imprinting analysis for fatness trait QTLs in pigs.
AB  - Quantitative trait loci (QTL) for fatness traits were reported recently in an
      experimental Meishan x Large White and Landrace F(2) cross. To further
      investigate the regions on pig Chr 2 (SSC2), SSC4, and SSC7, 25 additional
      markers from these regions were typed on 800 animals (619 F(2) animals, their
      F(1) parents, and F(0) grandfathers). Compared with the published maps, a
      modified order of markers was observed for SSC4 and SSC7. QTL analyses were
      performed both within the half-sib families as well as across families (line
      cross). Furthermore, a QTL model accounting for imprinting effects was tested.
      Information content could be increased considerably on all three chromosomes.
      Evidence for the backfat thickness QTL on SSC7 was increased, and the location
      could be reduced to a 33-cM confidence interval. The QTL for intramuscular fat on
      SSC4 could not be detected in this half-sib analysis, whereas under the line
      cross model a suggestive QTL on a different position on SSC4 was detected. For
      SSC2, in the half-sib analysis, a suggestive QTL for backfat thickness was
      detected with the best position at 26 cM. Imprinting analysis, however, revealed
      a genome-wise, significant, paternally expressed QTL on SSC2 with the best
      position at 63 cM. Our results suggest that this QTL is different from the
      previously reported paternally expressed QTL for muscle mass and fat deposition
      on the distal tip of SSC2p.

PMID- 10920236
TI  - Construction and characterization of a new bovine bacterial artificial chromosome
      library with 10 genome-equivalent coverage.

PMID- 10920237
TI  - Multi-phenotype behavioral characterization of inbred strains derived from wild
      stocks of Mus musculus.
AB  - Many aspects of mouse behavior have been studied by using only a relatively small
      sample of available laboratory strains. These laboratory mice were derived from
      the so-called "fancy mouse" and in most cases underwent extensive domestication
      before inbreeding. Thus, the behavioral repertoire of the laboratory mouse may be
      very different from that exhibited by stocks that have not been deliberately
      domesticated. Another inherent problem in analyzing mouse behavior is that
      genetic diversity is limited among currently available strains. In this respect,
      the use of strains that are derived from a variety of wild mice should provide a
      means to identifying novel behavioral phenotypes. We have investigated several
      behavioral phenotypes, using females of a number of mouse strains derived from
      wild mice of different subspecies, BFM/2, NJL, BLG2, HMI, CAST/Ei, KJR, SWN and
      MSM; a strain derived from fancy mice, JF1; and two laboratory strains, C57BL/6
      and DBA/1. In this report, tests for locomotor activity, light-dark transitions,
      passive and active avoidance, and nociception were conducted. The results show
      great diversity of behavioral patterns between strains in contrast to less within
      strain variability. We also found that two strains, KJR and SWN, both have good
      learning ability, whereas BLG2 mice exhibit impairment in both passive and active
      avoidance learning.

PMID- 10920238
TI  - Improvements in allelic discrimination of microsatellite markers using denaturing
      polyacrylamide gel electrophoresis.
AB  - Poor resolution, retarded progress of DNA through gels, and variable sizing of
      DNA fragments between and within gels hinder accurate genotyping of some simple
      sequence length polymorphism (SSLP) markers with the Perkin Elmer Applied
      Biosystems 377 Sequenator. These problems are similar to renaturation related
      problems observed in DNA sequencing gels. PCR products especially susceptible to
      these problems are shown to have higher melting temperatures (T(m)) than others.
      Gels containing increased concentrations of denaturants allow greater accuracy in
      allelic discrimination. This is especially beneficial where quantification is
      necessary.

PMID- 10920239
TI  - Cloning and characterization of human PREB; a gene that maps to a genomic region
      associated with trisomy 2p syndrome.
AB  - We have isolated the human homolog of a novel rodent gene that may be involved in
      the regulation of pituitary gene transcription. The human PREB gene encodes a
      predicted protein of 417 amino acids, exhibiting several sequences characteristic
      of the WD-motif protein family. PREB transcripts were detected in every human
      fetal and adult tissue examined, although a great variation in levels of
      expression was observed. PREB was mapped to human Chromosome 2p23, a region of
      the genome associated with partial trisomy 2p syndrome. Although variable, the
      common duplication phenotype includes facial abnormalities, skeletal defects,
      growth and mental retardation, congenital heart and neural tube defects, and
      abnormalities of the genitalia. We propose that PREB has a role during human
      development and that abnormal dosage of this transcription factor may be involved
      in some of the developmental abnormalities observed in patients with partial
      trisomy 2p.

PMID- 10920240
TI  - Comparative map alignment of BTA27 and HSA4 and 8 to identify conserved segments
      of genome containing fat deposition QTL.
AB  - Quantitative trait loci (QTL) associated with fat deposition have been identified
      on bovine Chromosome 27 (BTA27) in two different cattle populations. To generate
      more informative markers for verification and refinement of these QTL-containing
      intervals, we initiated construction of a BTA27 comparative map. Fourteen genes
      were selected for mapping based on previously identified regions of conservation
      between the cattle and human genomes. Markers were developed from the bovine
      orthologs of genes found on human Chromosomes 1 (HSA1), 4, 8, and 14. Twelve
      genes were mapped on the bovine linkage map by using markers associated with
      single nucleotide polymorphisms or microsatellites. Seven of these genes were
      also anchored to the physical map by assignment of fluorescence in situ
      hybridization probes. The remaining two genes not associated with an identifiable
      polymorphism were assigned only to the physical map. In all, seven genes were
      mapped to BTA27. Map information generated from the other seven genes not
      syntenic with BTA27 refined the breakpoint locations of conserved segments
      between species and revealed three areas of disagreement with the previous
      comparative map. Consequently, portions of HSA1 and 14 are not conserved on
      BTA27, and a previously undefined conserved segment corresponding to HSA8p22 was
      identified near the pericentromeric region of BTA8. These results show that BTA27
      contains two conserved segments corresponding to HSA8p, which are separated by a
      segment corresponding to HSA4q. Comparative map alignment strongly suggests the
      conserved segment orthologous to HSA8p21-q11 contains QTL for fat deposition in
      cattle.

PMID- 10920241
TI  - Why do we still find anonymous ESTs?
AB  - During recent years, there has been an exponential rise in the number of
      sequences accessible in the public databases. Despite this, a high percentage of
      partial sequences of cDNA (ESTs) submitted to the databases remain unrecognized
      (anonymous ESTs). This lack of similarities could be explained by several
      hypotheses: i) a different part of the transcript is present in the GenBank; ii)
      the transcript represents a novel gene not yet isolated in other species; iii)
      alternative splicing of the same gene in different species; iv) inaccurate
      sequence data; and/or v) the sequence of the transcript has diverged to the
      extent that it is not recognized as an ortholog. In the present study we selected
      a sample of 20 ESTs from a pool of 656 anonymous pig small intestine ESTs in
      order to investigate the possible cause for the lack of similarities with
      database entries. To test the significant hypotheses we carried out total
      sequencing of each insert along with zoo-blot and Northern-blot analysis.
      Extended analyses of the 20 ESTs showed significant matches to seven existing
      database entries, whereas 13 still did not show significant hits. The results are
      discussed in the context of the hypothesis listed above.

PMID- 10920242
TI  - A linkage map of distal mouse chromosome 4 in the vicinity of Ssm1, a strain
      specific modifier of methylation.

PMID- 10920243
TI  - Cell- and stage-specific expression of mage genes during mouse spermatogenesis.

PMID- 10920244
TI  - Tyrosinase gene variants in different rabbit strains.

PMID- 10920245
TI  - Assignation of highly polymorphic markers on a canine purebred pedigree.

PMID- 10920246
TI  - Mapping the RAIDD gene of chicken (Gallus gallus): identification of a region
      homologous to the mouse high-growth region.

PMID- 10920248
TI  - Porphyromonas gingivalis proteinases as virulence determinants in progression of
      periodontal diseases.
AB  - Porphyromonas gingivalis, one of the major causative agents of periodontal
      diseases, produces large amounts of arginine- and lysine-specific cysteine
      proteinases in cell-associated and secretory forms, which are now referred to as
      Arg-gingipain (Rgp) and Lys-gingipain (Kgp), respectively. A number of studies
      have revealed that these proteinases are closely associated with the
      periodontopathogenesis of this bacterium: destruction of periodontal connective
      tissues, disruption of host defense mechanisms, and development and maintenance
      of inflammation in periodontal pockets. With respect to the physiology of the
      bacterium, Rgp and Kgp are indispensable for it to obtain nutrients from the
      environment, since it cannot utilize saccharides as carbon/energy sources for
      growth and totally depends on peptides and amino acids that are provided from
      environmental proteins by Rgp and Kgp. Furthermore, proteolytic activities of Rgp
      and Kgp contribute to processing/maturation of various cell-surface proteins of
      P. gingivalis, such as fimA fimbrilin (a subunit of major fimbriae), 75-kDa
      protein (a subunit of minor fimbriae), hemagglutinins, and the hemoglobin
      receptor protein, which are important for the bacterium to colonize and
      proliferate in the gingival crevice and to invade the periodontium. These
      findings strongly indicate critical roles of Rgp and Kgp in the virulence of P.
      gingivalis.

PMID- 10920247
TI  - Positioning of five genes (CASK, ARX, SAT, IMAGE cDNAs 248928 and 253949) from
      the human X chromosome short arm with respect to evolutionary breakpoints on the
      mouse X chromosome.

PMID- 10920249
TI  - Molecular cloning and functional expression of cDNA encoding the cysteine
      proteinase inhibitor with three cystatin domains from sunflower seeds.
AB  - Two cysteine proteinase inhibitors, cystatins Sca and Scb, were previously
      isolated from sunflower seeds [Kouzuma et al. J. Biochem. 119 (1996) 1106-1113].
      A cDNA clone encoding a novel phytocystatin with three repetitive cystatin
      domains was isolated from a cDNA library of sunflower seeds using the Sca cDNA
      fragment as a hybridization probe. The cDNA insert comprises 1,093 bp and encodes
      282 amino acid residues. The deduced amino acid sequences of the domains are
      highly similar to each other (66-81%), sharing 65-90% identical residues with
      Sca. The cDNA was expressed in Escherichia coli cells, and then the recombinant
      sunflower multicystatin (SMC) was purified and its inhibitory activity toward
      papain was examined. SMC exhibited strong inhibitory activity toward papain, with
      a stoichiometry of 1:3, indicating that each cystatin domain independently
      functions as a potent cysteine proteinase inhibitor. Proteolysis of SMC with Asn
      specific proteinase suggested that post-translational processing by an Asn
      specific proteinase may give rise to mature Sca-like phytocystatins.

PMID- 10920250
TI  - Primary structure and autoproteolysis of brevilysin H6 from the venom of Gloydius
      halys brevicaudus.
AB  - The complete amino acid sequence of brevilysin H6 (H6), a zinc-protease isolated
      from Gloydius halys brevicaudus venom, was determined by a manual Edman
      degradation method. H6 has an amino-terminal pyroglutamic acid and consists of a
      total of 419 residues. An N-linked sugar chain is attached at Asn-181. The
      molecule is composed of three domains (metalloprotease, disintegrin-like and
      cysteine-rich domains), as commonly found in other high molecular mass
      metalloproteases from snake venoms. In the absence of calcium ions, H6 is
      autocatalytically degraded with a half-life of 47 min to give 29 and 45 kDa
      fragments, which correspond to residues 208-419 and 99-419 of H6, respectively.
      Thus, the autoproteolysis seemed to start from the cleavage of either the Leu(98)
      Leu(99) or Asp(207)-Ile(208) bond. Calcium ions suppressed both the formation of
      the 45 kDa fragment and the rate of autoproteolysis. Calcium ions also
      contributed to the stability of H6 against pH, heating, urea and cysteine. More
      than twenty-five peptide bonds adjacent to hydrophobic residues in the
      metalloprotease domain were progressively cleaved during the autoproteolysis.

PMID- 10920251
TI  - Structural analysis of N-linked sugar chains of human blood clotting factor IX.
AB  - The structures of N-glycans of human blood clotting factor IX were studied. N
      Glycans liberated by hydrazinolysis were N-acetylated and the reducing-end sugar
      residues were tagged with 2-aminopyridine. The pyridylamino (PA-) sugar chains
      thus obtained were purified by HPLC. Each PA-sugar chain was analyzed by two
      dimensional sugar mapping combined with glycosidase digestion. The major
      structures of the N-linked sugar chains of human factor IX were found to be
      sialotetraantennary and sialotriantennary chains with or without fucose residues.
      These highly sialylated sugar chains are located on the activation peptide of the
      protein.

PMID- 10920252
TI  - The steady-state kinetics of the enzyme reaction tested by site-directed
      mutagenesis of hydrophobic residues (Val, Leu, and Cys) in the C-terminal alpha
      helix of human adenylate kinase.
AB  - To elucidate whether the C-terminal region in human adenylate kinase participates
      in the interaction with the substrate (MgATP(2-) and/or AMP(2-)), hydrophobic
      residues (Val182, Val186, Cys187, Leu190, and Leu193) were substituted by site
      directed mutagenesis and the steady-state kinetics of fifteen mutants were
      analyzed. A change in the hydrophobic residues in the C-terminal domain affects
      the affinity for substrates (K(m)), that is, not only for MgATP(2-) but also for
      AMP(2-), and the catalytic efficiency (k(cat)). The results obtained have led to
      the following conclusions: (i) Val182 may interact with both MgATP(2-) and AMP(2
      ) substrates, but to a greater extent with MgATP(2-), and play a role in
      catalysis. (ii) Val186 appears to play a functional role in catalysis by
      interacting with both MgATP(2-) and AMP(2-) to nearly the same extent. (iii)
      Cys187 appears to play a functional role in catalysis. (iv) Leu190 appears to
      interact with both MgATP(2-) and AMP(2-) substrates but to a greater extent with
      AMP(2-). (v) Leu193 appears to interact with both MgATP(2-) and AMP(2-) but to a
      greater extent with AMP(2-). The activity of all mutants decreased due to the
      change in substrate-affinity. The closer the residue is located to the C-terminal
      end, the more its mutation affects not only MgATP(2-) but also AMP(2-) substrate
      binding. The hydrophobic alterations disrupt hydrophobic interactions with
      substrates and that might destabilize the conformation of the active site. The
      more C-terminal part of the alpha-helix appears to interact with AMP, as if it
      has swung out and rotated to cover the adenine moieties. The C-terminal alpha
      helix of human adenylate kinase appears to be essential for the interaction with
      adenine substrates by swinging out during catalysis.

PMID- 10920253
TI  - Unique heme environment at the putative distal region of hydrogen peroxide
      dependent fatty acid alpha-hydroxylase from Sphingomonas paucimobilis
      (peroxygenase P450(SPalpha).
AB  - Fatty acid alpha-hydroxylase from Sphingomonas paucimobilis is a hydrogen
      peroxide-dependent cytochrome P450 (P450) enzyme (P450(SPalpha)). In this study,
      heme-ligand exchange reactions of P450(SPalpha) were investigated using the
      optical spectroscopic method and compared with those of various P450s.
      Alkylamines (C >/= 5) induced changes in the spectrum of ferric P450(SPalpha) to
      one typical of a nitrogenous ligand-bound low-spin form of ferric P450, although
      their affinities were lower than those for other P450s, and a substrate, laurate,
      did not interfere with the binding in contrast with in the cases of other P450s.
      Other compounds having a nitrogen donor atom to the heme iron of P450, including
      pyridine or 1-methylimidazole, induced no change in the spectrum of P450(SPalpha)
      in either the ferric or ferrous state. Practically no spectral change was
      observed on the addition of alkyl isocyanides to ferric P450s. On the other hand,
      cyanide induced a change in the spectrum of ferric P450(SPalpha) to one
      characteristic of cyanide-bound form of ferric P450. The affinity of cyanide
      increased when the substrate was added, in contrast with in the cases of other
      P450s. Ferrous P450(SPalpha) combined with CO and alkyl isocyanides, and the
      affinity for CO was of the same order of magnitude as in the cases of other
      P450s. These findings suggest a unique heme environment of P450(SPalpha), in
      which most compounds usually acting as external ligands of ferric P450s are
      prevented from gaining access to the heme iron of P450(SPalpha). The unique
      properties of the hydroxylase reaction catalyzed by P450(SPalpha), where an
      oxygen atom of hydrogen peroxide but not of molecular oxygen is utilized and
      incorporated into a fatty acid at its alpha position, is possibly related with
      such a specific heme environment of this P450. A possible mechanism for the
      peroxygenase reaction of P450(SPalpha) is proposed.

PMID- 10920254
TI  - Molecular construction of a multidrug exporter system, AcrAB: molecular
      interaction between AcrA and AcrB, and cleavage of the N-terminal signal sequence
      of AcrA.
AB  - The AcrAB system of Escherichia coli is an intrinsic efflux protein with a broad
      substrate specificity. AcrA was thought to be localized in the periplasmic space,
      and to be linked to AcrB and TolC. The AcrAB-TolC system directly exports diverse
      substrates from the cell interior to the medium. In this study, we have
      determined the cellular localization of AcrA. By using the osmotic shock method,
      sucrose density gradient centrifugation, urea washing and Western blotting
      analysis, we reveal that AcrA is a peripheral inner membrane protein. A mutant
      plasmid encoding both the AcrA-TetBCt fusion protein and the AcrB-His fusion
      protein was constructed. Membrane vesicles prepared from cells expressing these
      fusion proteins were solubilized and AcrB-His was immunoprecipitated with an anti
      polyhistidine antibody. After SDS-PAGE, Western blotting was performed with anti
      TetBCt antiserum, resulting in the appearance of a 40 kDa band, indicating that
      AcrA co-precipitated with AcrB. Next we performed site-directed chemical labeling
      of Cys-introduced mutants of AcrA with [(14)C]N-ethylmaleimide. As judged from
      the labeling pattern and the molecular mass shift, the N-terminus of AcrA was
      removed and the mature protein is on the periplasmic surface. On the other hand,
      C25A mutants retained the N-terminal signal sequence on the cytoplasmic side of
      the membrane. We conclude that AcrA exists as a complex with AcrB on the
      periplasmic surface of the inner membrane after removal of the signal sequence.

PMID- 10920255
TI  - Intracellular degradation of histidine-rich glycoprotein mutants: tokushima-1 and
      2 mutants are degraded by different proteolytic systems.
AB  - We reported the first case of a congenital histidine-rich glycoprotein deficiency
      (HRG Tokushima) in which substitution of Gly85 with Glu (G85E) in the first
      cystatin domain resulted in intracellular degradation and a low plasma level of
      HRG [Shigekiyo, T. et al. (1998) Blood 91, 128-133]. Recently, we identified the
      gene mutation of a second case of HRG deficiency as a Cys223 to Arg (C223R)
      mutation in the second cystatin domain. To investigate the molecular and cellular
      bases of these deficiencies, we expressed these HRG mutants in baby hamster
      kidney (BHK) cells. Pulse-chase experiments in the absence and presence of
      various proteinase inhibitors revealed that, while wild-type HRG was completely
      secreted during 4-h chase periods, both the G85E and C223R mutants were only
      partially secreted and primarily degraded within the cells. The intracellular
      degradation of the C223R mutant was almost completely inhibited in the presence
      of a proteasome inhibitor, lactacystin, carbobenzoxy-leucyl-leucyl-leucinal or N
      acetyl-leucyl-leucyl-norleucinal, resulting in increased secretion of the C223R
      mutant, and thus implicating the proteasome system in this degradation process.
      In contrast, the sum of the amounts of the G85E mutant inside and outside the
      cells decreased during the chase periods even in the presence of the proteasome
      inhibitor, carbobenzoxy-leucyl-leucyl-leucinal or N-acetyl-leucyl-leucyl
      norleucinal, although proteasome-specific inhibitor lactacystin and one of the
      cysteine protease inhibitors, E-64-d, prevented the intracellular degradation.
      These results suggested that intracellular degradation of G85E HRG occurred to
      some extent through a hitherto unknown mechanism. Similar studies involving
      recombinant mutants in which Gly85 or Cys223 was replaced with several other
      amino acids revealed that proteins with mutations leading to the destruction of
      the predicted b-sheet structure of the cystatin domains were eliminated by the
      intracellular quality control system.

PMID- 10920256
TI  - Glutamate 83 is important for stabilization of domain-domain conformation of
      Thermus aquaticus glycerol kinase.
AB  - The gene glpK, encoding glycerol kinase (GlpK) of Thermus aquaticus, has recently
      been identified. The protein encoded by glpK was found to have an unusually high
      identity of 81% with the sequence of GlpK from Bacillus subtilis. Three residues
      (Arg-82, Glu-83, and Asp-244) of T. aquaticus GlpK are conserved in all the known
      GlpK sequences, including those from various bacteria, yeast and human. The roles
      that these three residues play in the catalytic mechanism were investigated by
      using site-directed mutagenesis to produce three mutants: Arg-82-Ala, Glu-83-Ala,
      and Asp-244-Ala. Replacement of Asp-244 by Ala resulted in a complete loss of
      activity, thus suggesting that Asp-244 is important for catalysis. Taking
      k(cat)/K(m) as a simple measure of catalytic efficiency, the mutants Arg-82-Ala
      and Glu-83-Ala were judged to cause 190- and 37,000-fold decrease, respectively,
      when compared to the wild-type GlpK. Thus, these three residues play a critical
      role in the catalytic mechanism. However, only mutant Glu-83-Ala was cleaved by
      alpha-chymotrypsin, and proteolysis studies showed that the mutant Glu-83-Ala
      involves a change in the exposure of Tyr-331 at the alpha-chymotrypsin site. This
      indicates a large domain conformational change, since the residues corresponding
      to Glu-83 and Tyr-331 in the Escherichia coli GlpK sequence are located in domain
      IB and domain IIB, respectively. The apparent conformational change caused by
      replacement of Glu-83 leads us to propose that Glu-83 is an important residue for
      stabilization of domain conformation.

PMID- 10920257
TI  - Substrate recognition and activation mechanism of D-amino acid oxidase: a study
      using substrate analogs.
AB  - We investigated the mechanism of recognition and activation of substrate by D
      amino acid oxidase (DAO) by thermodynamical and spectrophotometric methods using
      zwitterionic ligands [N-methylisonicotinate (NMIN), trigonelline, and homarine]
      and monoanionic ligands as model compounds of the substrate and the product. In
      terms of the charge within the substrate D-amino acid, monoanionic (e.g.,
      benzoate), zwitterionic (e.g., NMIN), and dianionic (e.g., terephthalate) ligands
      are thought to be good models for neutral, basic, and acidic amino acids,
      respectively, because when a substrate binds to DAO, as previously reported, the
      a-ammonium group (-NH(3)(+)) probably loses a proton to become neutral (-NH(2))
      before the oxidation. Zwitterionic ligands can also be good model compounds of
      product in the purple complex (the complex of reduced DAO with the product imino
      acid), because the imino nitrogen of the imino acid is in a protonated cationic
      form. We also discuss electrostatic interaction, steric effect, and charge
      transfer interaction as factors which affect the affinity of substrate/ligand for
      DAO. Monoanionic ligands have high affinity for neutral forms of oxidized and
      semiquinoid DAO, while zwitterionic ligands have high affinity for anionic forms
      of oxidized, semiquinoid, and reduced DAO; this difference was explained by the
      electrostatic interaction in the active site. The low affinity of homarine (N
      methylpicolinate) for oxidized DAO, as in the case of o-methylbenzoate, is due to
      steric hindrance: one of the ortho carbons of benzoate is near the phenol carbons
      of Tyr228 and the other ortho carbon is near the carbonyl oxygen of Gly313. The
      correlation of the affinity of meta- and para-substituted benzoates for oxidized
      DAO with their Hammet's s values are explained by the HOMO-LUMO interaction
      between the phenol group of Tyr224 and the benzene ring of benzoate derivative.
      The pK(a) of neutral flavin [N(3)-H of oxidized flavin, N(5)-H of semiquinoid
      flavin, and N(1)-H of reduced flavin] decreases by its binding to the apoenzyme.
      The magnitude of the decrement is oxidized flavin < semiquinoid flavin < reduced
      flavin. The largest factor in the substantially low pK(a) of reduced flavin in
      DAO is probably the steric hindrance between the hydrogen atom of H-N(1)(flavin)
      and the hydrogen atom of H-N of Gly315, which becomes significant when a hydrogen
      is bound to N(1) of flavin.

PMID- 10920258
TI  - Edge-to-face CH/pi interaction between ligand Phe-phenyl and receptor aromatic
      group in the thrombin receptor activation.
AB  - In the ligand/receptor interaction, the side chain phenyl group of phenylalanine
      (Phe) is involved in a so-called hydrophobic interaction, in which the Phe-phenyl
      group functions as a p element or merely as a hydrophobic element. The thrombin
      receptor-tethered ligand SFLLRNP consists of the Phe-2 residue essential for
      receptor activation. In order to explore the molecular characteristics of this
      Phe-2-phenyl group, a complete set of S/Phe/LLRNP peptides comprising six
      different difluorophenylalanine isomers [(F(2))Phe] was newly synthesized and
      assayed to evaluate their ability to induce the aggregation of human platelets.
      The assay results clarified several important structural elements to conclude
      that Phe-2-phenyl of S/Phe/LLRNP is in the edge-to-face CH/pi interaction with
      the receptor aromatic group, utilizing the Phe-phenyl edge along with adjacent
      benzene hydrogens at positions (2-3) or (5-6). It was also found that the
      fluorine atom at position 4 increases the acidity of the hydrogen mainly at its
      ortho position, resulting in a reinforcement of the CH/pi interaction and thus in
      an enhancement of biological activity. The H-->F replacement in the benzene ring
      was found to provide an effective structural examination to the Phe residue;
      i.e., to identify the hydrogens in the CH/pi interaction, and to strengthen the
      CH/pi interaction.

PMID- 10920260
TI  - Stabilization of human RNase 1 by introduction of a disulfide bond between
      residues 4 and 118.
AB  - In order to stabilize human RNase 1 by introduction of an intramolecular cross
      link, a mutant protein (4-118CL RNase 1), in which Arg4 and Val118 are replaced
      with cysteine residues and linked by a disulfide bond, was designed and expressed
      in Escherichia coli as inclusion bodies. The 4-118CL RNase 1 that refolded under
      redox conditions was a monomer without free SH groups and retained 11% of the
      activity of the wild-type recombinant RNase 1, indicating that the mutant enzyme
      was correctly folded with the formation of an additional disulfide bond between
      Cys4 and Cys118. From guanidium chloride denaturation experiments based on the
      assumption of a two-state transition for unfolding, it was demonstrated that the
      introduction of the present cross-link increased the thermodynamic stability of
      RNase 1 by 2.0 kcal/mol. This value was lower than that, 5.4 kcal/mol,
      theoretically calculated from the reduction of chain entropy of the unfolded
      state due to the introduction of the cross-link. These results suggest that the
      present cross-link also destabilized the folded state of RNase 1 by 3.4 kcal/mol.
      Along with the increase in the thermodynamic stability, the stability of RNase 1
      against trypsin digestion was also significantly increased by the introduction of
      this cross-link. It is likely, although not proven, that stabilized human RNases
      are favorable for clinical use, because human RNase-based immunotoxins should
      have long half-lives as to proteolytic degradation after endocytosis.

PMID- 10920259
TI  - Human MUC4 mucin cDNA and its variants in pancreatic carcinoma.
AB  - The human MUC4 gene is not expressed in normal pancreas; however, its
      dysregulation results in high levels of expression in pancreatic tumors. To
      investigate the tumor-associated expression, MUC4 cDNA was cloned from a human
      pancreatic tumor cell line cDNA expression library using a polyclonal antibody
      raised against human deglycosylated mucin and RT-PCR. Pancreatic MUC4 cDNA shows
      differences in 12 amino acid residues in the non-tandem repeat coding region with
      no structural rearrangement as compared with tracheal MUC4. The full-length MUC4
      cDNA includes a leader sequence, a serine and threonine rich non-tandem repeat
      region, a central large tandem repeat domain containing 48 bp repetitive units,
      regions rich in potential N-glycosylation sites, two cysteine-rich domains, EGF
      like domains, and a transmembrane domain. We also report the presence of a new
      EGF-like domain in MUC4 cDNA, located in the cysteine-rich region upstream from
      the first EGF-like domain. Four distinct splice events were identified in the
      region downstream of the central tandem repeat domain that generate three new
      MUC4 cDNA sequences (sv4, sv9, and sv10). The deduced amino acid sequences of two
      of these variants lack the transmembrane domain. Furthermore, two unique forms of
      MUC4 (MUC4/Y and MUC4/X) generated as a result of alternative splicing lack the
      salient feature of mucins, the tandem repeat domain. A high degree of
      polymorphism in the central tandem repeat region of MUC4 was observed in various
      pancreatic adenocarcinoma cell lines, with allele sizes ranging from 23.5 to 10.0
      kb. MUC4 mRNA expression was higher in differentiated cell lines, with no
      detectable expression in poorly differentiated pancreatic tumor cell lines.

PMID- 10920261
TI  - Dual pathways for the secretion of lysosomal cholesterol into a medium from
      cultured macrophages.
AB  - The removal of cholesterol from macrophages is important for reversing foam cell
      formation. In a previous study, we demonstrated that mouse peritoneal macrophages
      in culture secrete significant amounts of unesterified cholesterol from the
      lysosomes into the medium during endocytosis and subsequent metabolism of
      cholesterol-containing liposomes [Furuchi, T., Aikawa, K., Arai, H., and Inoue,
      K. (1993) J. Biol. Chem. 268, 27345-27348]. In this study, we found that at least
      two distinct mechanisms are involved in this process. The efflux of unesterified
      cholesterol into the medium was greatly suppressed by pregnenolone, an inhibitor
      of lysosomal cholesterol transport, but an appreciable proportion of the
      unesterified cholesterol was still released into the medium. Analysis of the
      medium containing the secreted cholesterol by NaBr density gradient
      ultracentrifugation revealed that the unesterified cholesterol was distributed in
      two different density peaks (bottom and d =/ approximately 1.1). The d =/
      approximately 1.1 peak material formed high-density lipoprotein (HDL)-like
      particles that were produced and secreted by the macrophages. The lipid
      components of these particles were phosphatidylcholine and sphingomyelin, while
      the sole protein component was apolipoprotein E (apo E). Treatment with
      pregnenolone completely abolished the production of these HDL-like particles but
      had little effect on the bottom fractions. These data indicate that macrophages
      release lysosomal cholesterol via both pregnenolone-sensitive and -insensitive
      pathways, and that only the cholesterol secreted through the pregnenolone
      sensitive pathway is associated with endogenously synthesized apo E-containing
      HDL-like particles. Moreover, we found that the pregnenolone-sensitive pathway
      operated independently of the presence or absence of exogenous HDL, whereas
      secretion via the pregnenolone-insensitive pathway was greatly stimulated by
      exogenously added HDL.

PMID- 10920263
TI  - NMR studies of model peptides of PHGGGWGQ repeats within the N-terminus of prion
      proteins: a loop conformation with histidine and tryptophan in close proximity.
AB  - The N-terminal region of the prion protein from human and mouse contains five
      tandem repeats with the consensus sequence of PHGGGWGQ. NMR studies were
      performed in water for two cyclic peptides, cyclo
      [C(1)R(2)Q(3)P(4)H(5)G(6)G(7)S(8)W(9)G(10)Q(11)R(12)D(13)C(14)] (C1) and cyclo
      [C(1)R(2)D(3)P(4)H(5)G(6)G(7)G(8)W(9)G(10)Q(11)P(12)H(13)G(14)G
      (15)G(16)W(17)G(18)Q(19)R(20)D(21)C(22)] (C2), which are cyclized by a disulfide
      bridge between the Cys residues at the N- and C-termini, and for their
      corresponding linear peptides (L1 and L2) which are formed by reduction. The
      patterns of the C(alpha)H chemical shift difference of these four peptide
      mimetics were very similar to those observed for the tandem repeats of human
      prion protein reported by other researchers. The medium-range NOE connectivities
      were found between the C(beta)H of the H5 and the proton of the W9 side chain for
      L1. The corresponding NOEs were also observed in H5-W9 and H13-W17 of L2 with
      ambiguity. These observations indicate that histidine (i) is in close proximity
      to tryptophan (i+4). d(alphaN) (i,i+2) NOE connectivities were observed between
      W9 and Q11 of L1 and L2, and d(NN) (i,i+1) NOE connectivities were also observed
      for G10-Q11 of L1 and L2 and for G18-Q19 of L2. Significantly lower temperature
      coefficients of amide proton chemical shifts were obtained for Q11 and Q19 of L2
      and C2. Structure calculations for L1 showed that HGG(G/S)W and (G/S)WGQ adopt a
      loop conformation and a beta-turn, respectively. These results strongly suggest
      that the tandem repeats within prion protein adopt a non-random structure.

PMID- 10920262
TI  - Molecular cloning and characterization of a unique 60 kDa/72 kDa antigen gene
      encoding enzyme I of the phosphoenolpyruvate: sugar phosphotransferase system
      (PTS) of Mycoplasma hyopneumoniae.
AB  - The recombinant clone expressing a 60 kDa (P60) antigen was isolated from
      Escherichia coli by screening a lambda EMBL3 genomic library using rabbit
      produced antiserum against Mycoplasma hyopneumoniae. Sequence analysis revealed
      that an interrupted (by a UGA codon) open reading frame coding for a 72 kDa
      protein (P72) may contain the P60 antigen gene. Western blot analysis with an
      anti-P60 monospecific antibody confirmed the presence of a P72 antigen from the
      total protein of M. hyopneumoniae, and a 72 kDa protein was also expressed in E.
      coli after changing the codon (UGA to UGG) by site-directed mutagenesis. BLAST
      (Basic Local Alignment Search Tool) comparison showed that the amino acid
      sequences of P72 share approximately 70% homology with the phosphotransferase
      enzyme I (PTSI) of bacteria and other mycoplasma species. The biological function
      of the P72 cytosolic protein was further confirmed by complementation using an E.
      coli ptsI mutant. The bacterial phosphoenolpyruvate-sugar phosphotransferase
      system (PTS) is known to mediate the uptake and phosphorylation of carbohydrates
      and to be involved in signal transduction. The immune responses of specific
      pathogen free (SPF) pigs and farm animals toward this unique antigen were
      observed. The transcription start positions of the PTSI gene were determined in
      M. hyopneumoniae and E. coli by primer extension experiments and the promoter
      site was also predicted.

PMID- 10920264
TI  - Studies on the structure-function relationship of the HNK-1 associated
      glucuronyltransferase, GlcAT-P, by computer modeling and site-directed
      mutagenesis.
AB  - All members of a glucuronyltransferase (GlcAT) gene family cloned to date contain
      four conserved regions (modules I-IV), which are widely located in the catalytic
      domain. In order to understand the biological significance of these modules, we
      investigated the structure-function relationship of GlcAT-P by means of the
      combination of site-directed mutagenesis and computer aided three-dimensional
      modeling. The wild-type and mutant GlcAT-Ps were expressed in Escherichia coli as
      glutathione-S-transferase (GST)-fused soluble proteins. Most of the mutants in
      which a polar amino acid within the modules was replaced with alanine lost their
      transferase activity almost completely, while all of the mutants in which the
      replacement was outside these modules retained the original catalytic activity. A
      three-dimensional (3-D) model of GlcAT-P was constructed by computer simulation
      with the three-dimensional structure of adenylate kinase (1AKE) as a template.
      This model predicted that the large catalytic domain of GlcAT-P forms a globular
      shape with a Rossmann-fold motif consisting of five alpha-helix and beta-sheet
      repeats. The putative catalytic pocket consisting mainly of modules I-III is
      surrounded by a cluster of polar amino acids, which are essential for the
      transferase activity and also for the binding to the acceptor substrate
      (essential amino acids), asialo-orosomucoid. There is the second cluster of
      essential amino acids almost on the opposite surface of the molecule, in which an
      aspartic acid repeat (DDD) is located. The biological significance of the second
      cluster is currently not clear but it may be associated with the interaction of
      the enzyme with modulation molecules, manganese and membrane phospholipids.

PMID- 10920265
TI  - Overexpression of salicylate hydroxylase and the crucial role of lys(163) as its
      NADH binding site.
AB  - Expression systems for the sal gene encoding salicylate hydroxylase from
      Pseudomonas putida S-1 were examined and some constructs were expressed in these
      systems. By cultivation of Escherichia coli BL21 (DE3)/pSAH8 in LB medium at 37
      degrees C with isopropyl-b-D-thiogalactopyranoside as the inducer, salicylate
      hydroxylase was overexpressed mainly in the form of inclusion bodies. Lower
      temperature cultivation at 20 degrees C after induction resulted in a large
      amount of the enzyme in the soluble form. The E. coli clone harboring the
      recombinant plasmid produced a 45 kDa protein that appeared to be
      electrophoretically and immunochemically identical to the P. putida enzyme and
      contained the same N-terminal amino acid sequence. This recombinant DNA product
      also exhibited properties characteristic of a flavoprotein and was fully
      functional as salicylate hydroxylase. Based on chemical modification of the
      salicylate hydroxylase from P. putida, Lys163 was previously proposed to be the
      NADH binding site. In this study, to obtain a better understanding of the
      predicted role of Lys163, this residue in the active center of salicylate
      hydroxylase was replaced with Arg, Gly, or Glu by conventional site-directed
      mutagenesis. Kinetic studies using these mutant enzymes and the recombinant
      enzyme revealed increases in apparent K(m) values for NADH in the order of wild
      type enzyme > K163R > K163G > K163E, with some decreases in V(max). Examination
      of the recombinant enzyme and K163G indicated that the pH dependency of K(m) on
      NADH with pK(a) 10.5 is lost by mutation despite the lack of changes in V(max)
      values, suggesting a requirement for the lysine residue as the NADH binding site.
      Based on these results, Lys163 is proposed to play a role in the binding of NADH
      at the active site through an ionic bond rather than playing a role in catalysis.

PMID- 10920266
TI  - Analyses of virus-induced homomeric and heteromeric protein associations between
      IRF-3 and coactivator CBP/p300.
AB  - Cellular genes including the type I interferon genes are activated in response to
      viral infection. We previously reported that IRF-3 (interferon regulatory factor
      3) is specifically phosphorylated on serine residues and directly transmits a
      virus-induced signal from the cytoplasm to the nucleus, and then participates in
      the primary phase of gene induction. In this study, we analyzed the molecular
      mechanism of IRF-3 activation further. The formation of a stable homomeric
      complex of IRF-3 between the specifically phosphorylated IRF-3 molecules
      occurred. While virus-induced IRF-7 did not bind to p300, the phosphorylated IRF
      3 complex formed a stable multimeric complex with p300 (active holocomplex).
      Competition using a synthetic phosphopeptide corresponding to the activated IRF-3
      demonstrated that p300 directly recognizes the structure in the vicinity of the
      phosphorylated residues of IRF-3. These results indicated that the
      phosphorylation of serine residues at positions 385 and 386 is critical for the
      formation of the holocomplex, presumably through a conformational switch
      facilitating homodimer formation and the generation of the interaction interface
      with CBP/p300.

PMID- 10920267
TI  - Studies on ATPase(GTPase) intrinsic to E. coli ribosomes.
AB  - (1) Escherichia coli 70S ribosomes showed intrinsic ATPase and GTPase activities,
      although they were much lower than those of rat liver ribosomes. The latter
      activity was higher than the former one. (2) The ATPase activity was inhibited by
      GTP and GMP-P(NH)P, and the GTPase activity was inhibited by ATP and AMP-P(NH)P,
      indicating a close relationship between the two enzymes. (3) Elongation
      components alone or in combination enhanced the ATPase activity, indicating the
      possible correlation of ribosomal ATPase with elongational components. (4)
      Vanadate at the concentrations that did not inhibit the GTPase activities of EF
      Tu and EF-G, depressed the poly(U)-dependent polyphe synthesis, suggesting that
      ribosomal ATPase (GTPase) participates in peptide elongation by inducing positive
      conformational changes of ribosomes required for the attachment of elongational
      components.

PMID- 10920268
TI  - Maintenance-type DNA methyltransferase is highly expressed in post-mitotic
      neurons and localized in the cytoplasmic compartment.
AB  - Maintenance-type DNA methyltransferase (Dnmt1) is usually down-regulated in non
      proliferating cells. In the present study, we detected significant expression of
      Dnmt1 protein in adult mouse brain where the majority of the cells are in a post
      mitotic state. A significant amount of Dnmt1 protein was fractionated into the
      post-nuclear fraction for both cerebrum and cerebellum. The Dnmt1 in this
      fraction was enzymatically active. An immunofluorescence study revealed that
      Dnmt1 protein was mainly expressed in neurons and seemed to be localized in the
      cytoplasmic compartment. Primary culturing of neurons confirmed the expression
      and localization of Dnmt1 in the cytoplasmic compartment. The findings that the
      Dnmt1 transcript in the brain utilized the somatic-type exon and that the
      apparent size of the Dnmt1 protein in the cytoplasm was identical to that in
      proliferating culture cells indicate that the cytoplasmic Dnmt1 in neurons was of
      the somatic-type.

PMID- 10920269
TI  - Purification and characterization of a novel heparinase from Bacteroides
      stercoris HJ-15.
AB  - A novel type of heparinase (heparin lyase, no EC number) has been purified from
      Bacteroides stercoris HJ-15, isolated from human intestine, which produces three
      kinds of heparinases. The enzyme was purified to apparent homogeneity by a
      combination of QAE-cellulose, DEAE-cellulose, CM-Sephadex C-50, hydroxyapatite,
      and HiTrap SP chromatographies with a final specific activity of 19.5
      mmol/min/mg. It showed optimal activity at pH 7.2 and 45 degrees C and the
      presence of 300 mM KCl greatly enhanced its activity. The purified enzyme
      activity was inhibited by Cu(2+), Pb(2+), and some agents that modify histidine
      and cysteine residues, and activated by reducing agents such as dithiothreitol
      and 2-mercaptoethanol. This purified Bacteroides heparinase is an eliminase that
      shows its greatest activity on bovine intestinal heparan sulfate, and to a lesser
      extent on porcine intestinal heparan sulfate and heparin. This enzyme does not
      act on acharan sulfate but de-O-sulfated acharan sulfate and N-sulfoacharan
      sulfate were found to be poor substrates. The substrate specificity of this
      enzyme is similar to that of Flavobacterial heparinase II. However, an internal
      amino acid sequence of the purified Bacteroides heparinase shows significant
      (73%) homology to Flavobacterial heparinase III and only 43% homology to
      Flavobacterial heparinase II. These findings suggest that the Bacteroidal
      heparinase is a novel enzyme degrading GAGs.

PMID- 10920270
TI  - Store depletion by caffeine/ryanodine activates capacitative Ca(2+) entry in
      nonexcitable A549 cells.
AB  - Capacitative Ca(2+) entry is essential for refilling intracellular Ca(2+) stores
      and is thought to be regulated primarily by inositol 1, 4,5-trisphosphate (IP(3))
      sensitive stores in nonexcitable cells. In nonexcitable A549 cells, the
      application of caffeine or ryanodine induces Ca(2+) release in the absence of
      extracellular Ca(2+) similar to that induced by thapsigargin (Tg), and Ca(2+)
      entry occurs upon the readdition of extracellular Ca(2+). The channels thus
      activated are also permeable to Mn(2+). The channels responsible for this effect
      appear to be activated by the depletion of caffeine/ryanodine-sensitive stores
      per se, as evidenced by the activation even in the absence of increased
      intracellular Ca(2+) concentration. Tg pretreatment abrogates the response to
      caffeine/ryanodine, whereas Tg application subsequent to caffeine/ryanodine
      treatment induces further Ca(2+) release. The response to caffeine/ryanodine is
      also abolished by initial ATP application, whereas ATP added subsequent to
      caffeine/ryanodine induces additional Ca(2+) release. RT-PCR analyses showed the
      expression of a type 1 ryanodine receptor, two human homologues of transient
      receptor potential protein (hTrp1 and hTrp6), as well as all three types of the
      IP(3) receptor. These results suggest that in A549 cells, (i) capacitative Ca(2+)
      entry can also be regulated by caffeine/ryanodine-sensitive stores, and (ii) the
      RyR-gated stores interact functionally with those sensitive to IP(3), probably
      via Ca(2+)-induced Ca(2+) release.

PMID- 10920271
TI  - Structural study of the N-terminal domain of the alpha subunit of Escherichia
      coli RNA polymerase solubilized with non-denaturing detergents.
AB  - The amino-terminal domain of the alpha subunit (alphaNTD) of Escherichia coli RNA
      polymerase consisting of 235 amino acid residues functions in the assembly of the
      alpha, beta, and beta' subunits into the core-enzyme. It has a tendency to form
      aggregates by itself at higher concentrations. For NMR structural analysis of
      alphaNTD, the solution conditions, including the use of non-denaturing
      detergents, were optimized by monitoring the translational diffusion coefficients
      using the field gradient NMR technique. Under the optimal conditions with
      taurodeoxycholate and with the aid of deuteration of the sample, alphaNTD gave
      triple-resonance spectra of good quality, which allowed the assignment of a large
      part of the backbone resonances. Analysis of the pattern of NOEs observed between
      the backbone amide and alpha-protons demonstrated that alphaNTD has three alpha
      helices and two beta-sheets. Although the secondary structure elements
      essentially coincide with those in the crystal structure, the larger of the two
      beta-sheets has two additional beta-strands. The irregular NOE patterns observed
      for the three positions in the beta-sheets suggest the presence of beta-bulge
      structures. The positions of the three helices coincide with the conserved
      sequence regions that are responsible for the subunit assembly.

PMID- 10920272
TI  - Mouse strain susceptibility to diethylnitrosamine induced hepatocarcinogenesis is
      cell autonomous whereas sex-susceptibility Is due to the micro-environment:
      analysis with C3H <--> BALB / c sexually chimeric mice.
AB  - In man, liver cancer is on the increase, especially in males. Sex differences
      also exist in rodent models. To elucidate the mechanisms, chimeric mice were
      produced by amalgamation of early embryos from high and low hepatocarcinogen
      susceptible strains, C3H and BALB / c. Tumor formation was initiated with 10 mg /
      kg of diethylnitrosamine at the ages of 7 and 14 days and mice were sacrificed at
      30 and 45 weeks. The chimeras were classified into XY <--> XY, XY <--> XX, XX <-
      > XY, and XX <--> XX in terms of sex chromosomes by means of polymerase chain
      reaction-simple sequence length polymorphism analysis (SSLP) using Y chromosome
      specific Sry primers in combination with the D3Mit21 marker. Liver lesions were
      analyzed histopathologically, by immunostaining using a C3H strain-specific
      antibody and by DNA in situ hybridization with the Y chromosome-specific
      digoxigenin-labeled Y353 / B probe. Sex and strain genotyping by SSLP analysis
      matched histological observations, confirming the reliability of our system. The
      strain differences in liver tumor numbers of each strain type in XY <--> XY and
      XX <--> XX subtypes of C3H <--> BALB / c chimeras were retained well (P < 0. 0001
      and P < 0.001, respectively), indicating a minimum influence of the C3H or BALB /
      c surrounding milieu on development of individual lesions. On the other hand,
      significant promotion of XX cell tumors was evident in phenotypically male
      sexually chimeric XY <--> XX and XX <--> XY chimeras for both C3H (P < 0.02) and
      BALB / c (P < 0.01) lesions compared to the XX <--> XX case. The results suggest
      the presence of hormonal or micro-environmental factors specific for males, which
      are not caused cell-autonomously. Basic strain differences, however, are
      determined by intrinsic genetic factors rather than the strain-dependent micro
      environment.

PMID- 10920273
TI  - Chemopreventive effects of coumaperine from pepper on the initiation stage of
      chemical hepatocarcinogenesis in the rat.
AB  - This study was designed to investigate the chemopreventive action of three
      natural products, coumaperine, aurapten and an extract from rosemary, against the
      initiation stage of rat hepato-carcinogenesis. Coumaperine has been isolated from
      white pepper as a naturally occurring antioxidative agent, but its potential
      modifying effects on carcinogenesis remain unclear. In experiment 1, a
      modification of the model developed by Tsuda et al. was applied, with assessment
      of numbers and areas of induced glutathione S-transferase placental form (GST-P)
      positive hepatocellular foci in male F344 rats. Coumaperine, aurapten and the
      extract from rosemary were administered i.g. at 100 mg / kg / day once daily for
      5 days with initiation by diethylnitrosamine (DEN) on day 4 (20 mg / kg, i.p.).
      Numbers and areas of GST-P-positive foci in each group given test chemicals
      tended to be decreased as compared to the vehicle control group values,
      significance being achieved for number with coumaperine. Experiment 2 was planned
      to investigate the mechanism of the inhibitory effects of coumaperine. Livers at
      8 h after initiation by DEN were examined with coumaperine administered at 100 mg
      / kg / day once daily for 3 days. Proliferating cell nuclear antigen (PCNA)
      positive cells tended to be decreased as compared to the vehicle control, but no
      effects on apoptosis or cytochrome P-450 (CYP) 2E1 expression were apparent. Our
      results suggest that coumaperine provides protection against initiation of
      hepatocarcinogenesis, and that this is related to inhibition of cell
      proliferation.

PMID- 10920274
TI  - Analyses of oxidative DNA damage and its repair activity in the livers of 3'
      methyl-4-dimethylaminoazobenzene-treated rodents.
AB  - We measured the levels of 8-hydroxyguanine (8-OH-Gua) and its repair activity in
      the livers of the Donryu rat, the carcinogen-resistant DRH rat, and the ddy
      mouse, which were fed a 0.06% 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB)
      containing diet. In a short-term rat experiment (maximum 2 months), 3'-MeDAB did
      not increase the 8-OH-Gua levels in the livers of the two rat strains, although
      it significantly increased the repair activity in only the Donryu rat liver at 1
      and 2 months. After long-term 3'-MeDAB administration to the ddy mouse (8
      months), the levels of 8-OH-Gua and its repair activity were increased in the
      liver by 3.6-fold and 1.6-fold, respectively. These experiments suggest that 3'
      MeDAB increases 8-OH-Gua generation in rodent liver DNA and the 8-OH-Gua repair
      assay is a reliable marker of cellular oxidative stress induced by carcinogens.

PMID- 10920275
TI  - Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional
      activity in colon cancer cells: structure-activity relationship.
AB  - Cyclooxygenase-2 (COX-2) plays an important role in carcinogenesis. Investigation
      of the suppressive action of twelve flavonoids of different chemical classes on
      the transcriptional activity of the COX-2 gene in human colon cancer DLD-1 cells
      using a reporter gene assay have revealed quercetin to be the most potent
      suppressor of COX-2 transcription (IC50 = 10.5 microM), while catechin and
      epicatechin showed weak activity (IC50 = 415.3 microM). Flavonoids have three
      heterocyclic rings as a common structure. A structure-activity study indicated
      that the number of hydroxyl groups on the B ring and an oxo group at the 4
      position of the C ring are important in the suppression of COX-2 transcriptional
      activity. A low electron density of the oxygen atom in the hydroxyl group of the
      A ring was also important. Further examination of the role of the hydroxyl group
      in the A ring showed that bromination of resacetophenone to give 3,5-dibromo-2,4
      dihydroxyacetophenone resulted in a 6.8-fold increase in potency for suppressing
      COX-2 promoter activity. These results provide a basis for the design of improved
      suppressors of COX-2 transcriptional activity.

PMID- 10920276
TI  - Preferential occurrence of breast carcinomas with loss of chromosome 16q and der
      (16) t (1;16) / der (1;16) in middle-aged patients with hyperplasia of mammary
      glands.
AB  - Structural and numerical alterations of chromosome 16 are considered to be
      commonly involved in the genesis of breast cancer. To reveal etiological factors
      that predispose cells to these alterations, we examined the frequencies of
      chromosome 16 aneusomy, 16q loss and 1;16 fusion indicating der (16) t (1;16) /
      der (1;16) by multi-color fluorescence in situ hybridization in 46 tumors
      resected mostly from young ( </= 34 years old) or elderly ( >/= 75 years old)
      women, and compared the results with those in a patient group representing a
      common age distribution of Japanese patients in whom chromosome 16 status in the
      tumor had already been studied. The correlation of these chromosome 16
      alterations with age, hyperplasia in adjacent mammary glands, cancer history, and
      obesity indices was investigated in a total of 244 patients. In the present 46
      tumors, the frequency of 16q loss and der (16) t (1;16) did not differ between 20
      younger patients (30% and 15%) and 23 elderly patients (43% and 13%). However,
      the incidences of 16q loss and der (16) t (1;16) were low in comparison with the
      values of 64% and 38% in the 198 Japanese patients representing the common age
      distribution (P < 0.001). In addition, 16q loss and der (16) t (1;16) were more
      frequent in tumors arising in hyperplastic mammary glands (68%, 44%) than in
      those without (52%, 24%) (P < 0.01). Such correlations were not evident for 16cen
      aneusomy. Other etiological factors examined were not correlated with these
      chromosome 16 alterations. The 16q loss and der (16) t (1;16) formation were more
      frequently involved in the development of breast cancer in middle-aged patients
      than in young and elderly patients. High-level estrogens and / or sensitivity of
      mammary glandular cells to estrogens might induce breast cancers with structural
      changes of chromosome 16.

PMID- 10920277
TI  - Mutation analysis of the PTEN / MMAC1 gene in Japanese patients with Cowden
      disease.
AB  - Cowden disease (CD), also known as multiple hamartoma syndrome, is an autosomal
      dominant cancer syndrome associated with high risk of breast and thyroid cancer.
      Recently, germline mutations in PTEN / MMAC1, which has nine exons encoding a
      dual specificity phosphatase with homology to tensin and auxilin, have been
      identified on chromosome 10q23 in some 40 to 80% of CD patients. Our polymerase
      chain reaction amplification and sequence analysis of all coding regions
      identified five different mutations including four novel germline mutations among
      5 of 12 unrelated Japanese CD patients. The novel findings included a missense
      mutation (G --> T) at nucleotide 1004 in exon 8 resulting in an arginine-to
      leucine change at codon 335 (R335L), two novel splice-site mutations (209 +
      1delGT and 209 + 1delGTAA) in intron 3, and insertion of G at nucleotide 632 in
      exon 6 (632insG). We also detected a nonsense mutation (C --> T) at nucleotide
      697 producing R233X in exon 7, which has been reported previously. From reported
      phenotypic data concerning CD patients from five different families who had the
      R233X mutation, it may be suggested that R233X mutation correlates with
      macrocephaly. Although previous reports have implicated exon 5 as a "hot spot,"
      we found no mutation in exon 5.

PMID- 10920278
TI  - Bcl-2 inhibits calcineurin-mediated Fas ligand expression in antitumor drug
      treated baby hamster kidney cells.
AB  - It is well known that human leukemia cells, such as HL-60 and U937 are sensitive
      to antitumor drugs, but human normal lung fibroblasts, such as WI-38 cells are
      resistant to the drugs. However, the mechanisms of the different responses to
      apoptosis in these cell lines remain unclear. We report here that an increase of
      Fas and Fas ligand (FasL) expression was required for antitumor drug-induced
      apoptosis in WI-38 and baby hamster kidney (BHK) cells, but not in HL-60 cells.
      Then, we used BHK cells transfected with the bcl-2 gene to investigate the
      involvement of complex formation of Bcl-2 and calcineurin. Calcineurin was
      imported to the nucleus in response to the drug treatment. Overexpression of Bcl
      2 and cyclosporin A treatment inhibited the nuclear import and FasL expression,
      and as a result, both inhibited apoptosis. Although a caspase inhibitor, z-Asp
      CH2-DCB, suppressed the drug-induced apoptosis, it failed to inhibit the drug
      induced expression of Fas and FasL. These findings suggest that initially the Fas
      / FasL system is activated by calcineurin-dependent transcription followed by
      activation of the downstream caspase cascade resulting in antitumor drug-induced
      apoptosis in BHK cells, but not in HL-60 cells. Furthermore, Bcl-2 inhibits the
      nuclear import of calcineurin and suppresses calcineurin-mediated FasL expression
      during antitumor drug-induced apoptosis.

PMID- 10920279
TI  - A novel experimental mouse model of peritoneal dissemination of human gastric
      cancer cells: different mechanisms in peritoneal dissemination and hematogenous
      metastasis.
AB  - We established a new cell line, AZ-P7a, with high peritoneal-metastatic potential
      in nude mice. AZ-P7a cells were derived from the human gastric carcinoma line AZ
      521, which has low capacity for peritoneal dissemination. AZ-P7a cells developed
      peritoneal metastasis in 11 / 14 (78.6%) mice, whereas the parental AZ-521 cells
      developed metastasis in 2 / 6 (33.3%) mice. The metastatic foci in the peritoneum
      showed essentially the same histological appearance as those induced by parental
      cells. The tumorigenicity and the motile activity of AZ-P7a cells were stronger
      than those of the parental AZ-521 cells; in contrast, adhesion to the
      extracellular matrix and the production of vascular endothelial growth factor by
      AZ-P7a cells were decreased. In fluorescence-activated cell sorter (FACS)
      analysis, AZ-P7a cells expressed significantly greater levels of integrins
      alpha2, alpha3, alpha5, alpha6 and alphavbeta5, as compared with AZ-521 cells.
      However, alpha1, alpha4, alphavbeta3, hCD44H, hCD44v3, hCD44v6 and hCD44v10 were
      not expressed in either cell line. AZ-P7a cells developed no liver metastasis
      when administered by the intrasplenic injection method, though the highly liver
      metastatic cell line AZ-H5c showed the same rate of peritoneal dissemination as
      that exhibited by AZ-P7a cells after intraabdominal injection. These findings
      suggested that the mechanism of peritoneal dissemination differed from that of
      hematogenous metastasis. Moreover, the latter appears to be controlled by more
      complex mechanisms than the former. Thus, this cell line might be useful for
      investigating the mechanism of peritoneal dissemination of human gastric cancer.

PMID- 10920280
TI  - Effect of angiostatin on liver metastasis of pancreatic cancer in hamsters.
AB  - The liver is the most common site of metastasis in pancreatic cancer, and there
      are no promising strategies to treat it. Angiostatin, a kringle-containing
      fragment of plasminogen, is a potent inhibitor of angiogenesis. The effect of
      angiostatin on liver metastasis in pancreatic cancer was investigated by using
      our established hamster model of liver metastasis. Pancreatic cancer cells (PGHAM
      1, 1 x 10(6)) derived from N-nitrosobis(2-oxopropyl)amine (BOP)-induced
      pancreatic tumor in Syrian golden hamsters were transplanted into the spleen of
      female hamsters, and the animals were subcutaneously injected with angiostatin
      and saline. Subsequently, the macroscopic appearance of liver surface metastases
      was evaluated. In addition, histological sections of the liver metastases were
      analyzed for neovascularization, proliferation, and apoptosis on the basis of von
      Willebrand factor, argyrophilic nucleolar organizer region (Ag-NOR), and TdT
      mediated dUTP-biotin nick end labeling (TUNEL) staining, respectively. The
      results showed significant tumor growth retardation and inhibition of
      angiogenesis in metastatic liver tumors in response to treatment with
      angiostatin. Moreover, the metastases remained in a nearly dormant state due to a
      balance between apoptosis and proliferation of the tumor, with no detectable side
      effects. This is the first experimental trial of angiostatin on pancreatic cancer
      and liver metastasis. The results suggest that angiostatin therapy could be
      effective against liver metastases of pancreatic cancer.

PMID- 10920281
TI  - Changes in the sensitivity of intratumor cells during fractionated tirapazamine
      administration.
AB  - Mice bearing solid tumors received 10 intraperitoneal administrations of 5-bromo
      2'-deoxyuridine (BrdU) to label the proliferating (P) tumor cells. Then, as a
      priming treatment, tirapazamine (TPZ) was intraperitoneally administered.
      Further, 0 through 48 h later, the tumor-bearing mice received TPZ again at
      various doses. The tumor cells were isolated and incubated with a cytokinesis
      blocker. The micronucleus (MN) frequencies in cells with and without BrdU
      labeling, which were regarded as P and quiescent (Q) cells at the priming
      treatment, respectively, were determined using immunofluorescence staining for
      BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the
      tumors that were not pretreated with BrdU. In addition, P cell ratios in the
      tumors at the second treatment were determined using immunofluorescence staining
      for P cell nuclear antigen. In each cell fraction, the longer the interval
      between the two treatments, the higher was the sensitivity to TPZ, except 1 h
      after the priming treatment. More than 24 h later, total and P cells, especially
      P cells, showed significantly higher sensitivity to TPZ than in the case of a
      single TPZ treatment. The longer the period between the two TPZ treatments, the
      lower was the P cell ratio at the second treatment. These findings were thought
      to indicate that the use of TPZ in the treatment of solid tumors causes a shift
      from the P to the Q state in vivo.

PMID- 10920282
TI  - Characterization of the interaction of TZT-1027, a potent antitumor agent, with
      tubulin.
AB  - TZT-1027, a derivative of dolastatin 10 isolated from the Indian Ocean sea hare
      Dolabella auricularia in 1987 by Pettit et al., is a potent antimicrotubule
      agent. We have compared the activity of TZT-1027 with that of dolastatin 10 as
      well as the vinca alkaloids vinblastine (VLB), vincristine (VCR) and vindesine
      (VDS). TZT-1027 and dolastatin 10 inhibited microtubule polymerization
      concentration-dependently at 1 - 100 microM with IC50 values of 2.2 +/- 0.6 and
      2.3 +/- 0.7 microM, respectively. VLB, VCR and VDS inhibited microtubule
      polymerization at 1 - 3 microM with IC50 values of 2.7 +/- 0.6, 1.6 +/- 0.4 and
      1.6 +/- 0.2 microM, respectively, but showed a slight decrease in inhibitory
      effect at concentrations of 10 microM or more. TZT-1027 also inhibited monosodium
      glutamate-induced tubulin polymerization concentration-dependently at 0.3 - 10
      microM, with an IC50 of 1.2 microM, whereas VLB was only effective at 0.3 - 3
      microM, with an IC50 of 0.6 microM, and caused so-called "aggregation" of tubulin
      at 10 microM. Scatchard analysis of the binding data for [(3)H]VLB suggested one
      binding site (Kd 0.2 +/- 0.04 microM and Bmax 6.0 +/- 0.26 nM / mg protein),
      while that for [(3)H]TZT-1027 suggested two binding sites, one of high affinity
      (Kd 0.2 +/- 0.01 microM and Bmax 1.7 +/- 0.012 nM / mg protein) and the other of
      low affinity (Kd 10. 3 +/- 1.46 microM and Bmax 11.6 +/- 0.83 nM / mg protein).
      [(3)H]TZT-1027 was completely displaced by dolastatin 10 but only incompletely by
      VLB. [(3)H]VLB was completely displaced by dolastatin 10 and TZT-1027.
      Furthermore, TZT-1027 prevented [(3)H]VLB from binding to tubulin in a non
      competitive manner according to Lineweaver-Burk analysis. TZT-1027 concentration
      dependently inhibited both [(3)H]guanosine 5'-triphosphate (GTP) binding to and
      GTP hydrolysis on tubulin. VLB inhibited the hydrolysis of GTP on tubulin
      concentration-dependently to a lesser extent than TZT-1027, but no inhibitory
      effect of VLB on [(3)H]GTP binding to tubulin was evident even at 100 microM.
      Thus, TZT-1027 affected the binding of VLB to tubulin, but its binding site was
      not completely identical to that of VLB. TZT-1027 had a potent inhibitory effect
      on tubulin polymerization and differed from vinca alkaloids in its mode of action
      against tubulin polymerization.

PMID- 10920283
TI  - Combination therapy with vascular endothelial growth factor neutralizing antibody
      and mitomycin C on human gastric cancer xenograft.
AB  - Antiangiogenic therapy has been proposed as a new strategy for the treatment of
      solid tumors. To enhance the therapeutic effect of antiangiogenic agents,
      combination with conventional anticancer therapy should be investigated. In the
      present study, we investigated the therapeutic effect of the combination of
      vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin
      C (MMC) on MT-2, a human gastric cancer xenograft. When small pieces of MT-2 were
      transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks
      after transplantation. The VEGF Ab (100 micro g / mouse) was administered i.p. in
      the VEGF Ab group (n = 14) and the combination group (n = 16) twice a week from
      day 10 after transplantation. MMC (2 mg / kg) was administered in the MMC group
      (n = 16) and the combination group (n = 16) on days 10, 17 and 24 after
      transplantation. Compared with the control group, in which saline solution was
      administered i.p., all three treatments inhibited tumor growth significantly and
      the effects of MMC and combination therapy were potent. Liver metastases were
      also inhibited significantly by the administration of VEGF Ab alone, MMC alone or
      combination therapy. Liver metastasis developed in 9 mice of the control group, 3
      of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in
      the combination therapy group. However a significant body weight loss and a
      decrease in spleen weight were observed in the MMC and combination groups, with
      no significant difference between the two groups. These results suggest that
      combination therapy with VEGF Ab and MMC may be a potent therapy for human
      gastric cancer.

PMID- 10920284
TI  - Photodynamic therapy for experimental tumors using ATX-S10(Na), a hydrophilic
      chlorin photosensitizer, and diode laser.
AB  - ATX-S10(Na), a hydrophilic chlorin photosensitizer having an absorption maximum
      at 670 nm, is a candidate second-generation photosensitizer for use in
      photodynamic therapy (PDT) for cancer treatment. The effectiveness of PDT using
      ATX-S10(Na) and a diode laser for experimental tumors was evaluated in vitro and
      in vivo. In-vitro PDT using ATX-S10(Na) and the diode laser showed drug
      concentration-, laser dose- and drug exposure time-dependent cytotoxicity to
      various human and mouse tumor cell lines. In Meth-A sarcoma-implanted mice,
      optimal PDT conditions were found where tumors were completely eliminated without
      any toxicity. Against human tumor xenografts in nude mice, the combined use of 5
      mg / kg ATX-S10(Na) and 200 J / cm(2) laser irradiation 3 h after ATX-S10(Na)
      administration showed excellent anti-tumor activity, and its efficacy was almost
      the same as that of PDT using 20 mg / kg porfimer sodium and a 100 J / cm(2)
      excimer dye laser 48 h after porfimer sodium injection. Microscopic observation
      of tumor tissues revealed that PDT using ATX-S10(Na) and the diode laser induced
      congestion, thrombus and degeneration of endothelial cells in tumor vessels,
      indicating that a vascular shutdown effect plays an important role in the anti
      tumor activity of PDT using ATX-S10(Na) and the diode laser.

PMID- 10920286
TI  - Competing interest.

PMID- 10920285
TI  - Diagnostic usefulness of telomerase activity in nasopharyngeal carcinoma.
AB  - Telomeres are specialized structures at the ends of eukaryotic chromosomes which
      are composed of simple repetitive G-rich hexameric sequences. Activation of
      telomerase, a ribonucleoprotein that synthesizes telomeric DNA, is found in most
      malignant tumors. However, little data is available concerning the correlation
      between telomerase activity and NPC (nasopharyngeal carcinoma). In this study,
      telomerase activation was determined using the TRAP (telomerase repeat
      amplification protocol) assay in 62 nasopharyngeal biopsies (25 NPC, 25 non
      malignant nasopharyngeal lymphoid tissues, 12 post-irradiated nasopharyngeal
      tissues). The results showed that strong telomerase activity was present in both
      NPC and non-malignant nasopharyngeal biopsies. Post-irradiated nasopharyngeal
      samples had a significantly lower telomerase activity than NPC and non-malignant
      nasopharyngeal lymphoid tissues. It is well known that nasopharyngeal tissue is
      infiltrated by numerous lymphocytes, which might retain telomerase activity.
      Therefore, the finding that the telomerase activation was lowest in post
      irradiated nasopharyngeal tissues is reasonable because of the destruction of
      activated lymphocytes and NPC by radiation. NPC biopsies with positive lymph node
      involvement exhibited higher levels of telomerase compared to those without lymph
      node involvement. Our data indicate a positive association between telomerase
      activity and tumor potential for lymphatic spreading in limited local tumors. In
      addition, telomerase activity may be useful as a diagnostic marker in the
      detection of tumor cells in recurrent NPC, but not in primary NPC.

PMID- 10920287
TI  - 'The trouble with sex - it always gets in the way': an evaluation of a peer
      produced teenage pregnancy video.
AB  - This paper describes the development and pilot evaluation of a peer-produced
      video, produced for use as part of North Staffordshire's Personal and Social
      Education school programme. A number of studies carried out in the area,
      including a recent audit into post-coital contraception in the under 20s, have
      shown that young people need to know how to access contraceptive services.
      Background surveys also suggest that young people need to be aware of the wider
      issues implicit in contraception. The impetus for the video came from the Advice
      Centres for the under Twenties (ACT) Working Party, who produced the video
      together with Staffordshire University's Media Studies Department and a local
      high school drama group. The video was intended for use in schools, and was
      designed to be complimentary to an updated and standardised teaching pack, which
      was already in preparation. The pilot study showed the video to be beneficial as
      a stand-alone intervention, principally to promote active discussion on topics
      that might otherwise be difficult to approach. A comparison of responses before
      and after the educational session demonstrated an improvement in knowledge in
      most areas. Further objective evaluation of the combined video and teaching pack
      is now necessary.

PMID- 10920288
TI  - A review of bone mineral density scans referred by a community-based menopause
      clinic in 1997.
AB  - Osteoporosis is a growing public health issue for the UK's ageing population.
      Many older women want know if they are at risk of osteoporosis and if preventive
      treatment, particularly in the form of hormone replacement therapy (HRT), would
      be advisable. This results in many women being referred for bone mineral density
      (BMD) scanning, whether or not they have recognised risk factors for
      osteoporosis. We present the results of a review of 228 referrals for BMD scan
      from a community-based menopause clinic. The results are categorised by the
      indications for the scan. The implications for the future of BMD investigations
      are considered in the light of ongoing discussion about population screening.

PMID- 10920290
TI  - Clinical performance of the levonorgestrel intra-uterine system in routine use by
      the UK Family Planning and Reproductive Health Research Network: 12-month report.
AB  - Doctors working in general practice and at family planning clinics throughout the
      UK who collaborate in the UK Family Planning and Reproductive Health Research
      Network were responsible for the fitting of 692 Levonorgestrel Intra-uterine
      Systems (LNG IUS). This study was undertaken to determine the performance of the
      LNG IUS in British women in routine clinical use. The 12 months cumulative life
      table event rates were: pregnancy 0.6, expulsion 4.5. The continuation rate was
      70.6. Removals were also required for side effects, which may be due to absorbed
      levonorgestrel, the removal rate being 7.4. Positive effects include effective
      contraception and considerably reduced quantity of bleeding for most
      participants. A need was identified to counsel women about the early bleeding
      problems, including the possibility of oligomenorrhoea or amenorrhoea. This is
      considered to be very important as it will help women to persevere so that they
      can enjoy the longer-term benefits.

PMID- 10920289
TI  - Repeated use of hormonal emergency contraception by younger women in the UK.
AB  - A cohort of women aged 14-29 in 1993 was identified from the General Practice
      Research Database and followed up for a period of 4 years. Patient files were
      searched for evidence of use of emergency contraception and regular
      contraception. Of the 95 007 women, 15 105 (16%) had received emergency
      contraception during the study period (an average of 5% per annum). There was a
      small year on year increase in uptake of emergency contraception between 1994 and
      1997. Only 4% of emergency contraception users received emergency contraception
      more than twice in any year. More than 70% of those who had no previous record of
      use of regular contraception had used regular contraception within 1 year of
      using emergency contraception. Teenagers were more likely than other age groups
      to use emergency contraception, to be repeat users of emergency contraception and
      to fail to start regular contraception after first use of emergency contraception
      until later in the study period. These results disprove the notion of widespread
      repeated use of emergency contraception. They show that provision of an emergency
      contraception service does not result in failure to initiate regular
      contraception or abandonment of regular contraception; rather they show many
      women using regular contraception for the first time after use of emergency
      contraception.

PMID- 10920291
TI  - Clinical performance of the Nova-T380 IUD in routine use by the UK Family
      Planning and Reproductive Health Research Network: 12-month report.
AB  - Doctors working in general practice and at family planning clinics throughout the
      UK who collaborate in the UK Family Planning and Reproductive Health Research
      Network were responsible for the fitting of 572 Nova-T380 intra-uterine
      contraceptive devices (IUDs). The Nova-T (and formerly the identical Novagard)
      IUDs have copper with a surface area of 200 mm(2). The device used in this study,
      the Nova-T380, has copper with a surface area of 380 mm(2). The purpose of the
      study was to evaluate the pregnancy and complication rates of this new device,
      with its increased area of copper, in comparison with other published results, in
      the clinical setting of British general practice and family planning clinics. The
      12-month cumulative life-table event rates were: pregnancy 0.8, expulsion 5.6,
      removal for bleeding or bleeding and pain 11.0. The continuation rate was 73.4.
      The pregnancy rate at 12 months showed good contraceptive performance. The
      increased surface area of copper was not associated with a reduced pregnancy
      rate, but as this was not a direct comparative study with the Nova-T, the
      influence of the increased area of copper must remain somewhat uncertain. This
      study found the discontinuation rate for bleeding problems and pain with bleeding
      to be higher than in other published studies. Other event rates were consistent
      with other published studies.

PMID- 10920292
TI  - What if the audit commission visited you?
AB  - Readers will be familiar with high profile media items, like the Audit Commission
      investigating national public institutions, and publicising rigorous critiques of
      their 'value for money'. Family planning (FP) services may be interested to learn
      that the Audit Commission also perform 'district audits' (nothing to do with
      'clinical audit') and that these can analyse broader concerns to do with quality
      of patient care and acceptability of services, not just efficiency. 'Out of the
      blue' our service was the focus of such a district audit conducted over just 3
      weeks. We were asked what areas, apart from 'value for money', we would like
      investigated. We were keen to measure if our efforts of collaboration with
      Primary Care and other agencies had been effective. We learned that there is a
      national system (DATIS) to compare each FP service's expenditure per thousand
      patients. We also learned that being the subject of such an investigation need
      not be a threatening experience, and can be an opportunity to review quality of
      care and demonstrate our cost effectiveness. This account is the report of the
      district audit team of our service and our attempts at collaboration.

PMID- 10920293
TI  - Developing primary care services for young people.
AB  - The Cornwall and Isles of Scilly Health Promotion Service and Cornwall Youth
      Service have been working in partnership to facilitate the planning and promotion
      of high quality attractive and relevant designated health services for young
      people. This partnership arose from a joint project in North Cornwall looking at
      unwanted teenage pregnancies. It involved research with young people about their
      perspective of health services in their area, and a theatre in education project
      with the Barbican Theatre working with primary health care teams to raise
      awareness about the issues relating to health care for young people. The team
      have presented their work at several conferences, it has won a NHS 50 National
      Award sponsored by Glaxo-Wellcome, and has attracted much interest locally and
      nationally from policy makers and practitioners. This paper describes how the
      team came together, the various stages in the development and execution of the
      project, the outcomes and recommendations

PMID- 10920294
TI  - Empathy in the afternoon.
AB  - Empathy - the power of understanding and imaginatively entering into another
      person's feelings.

PMID- 10920296
TI  - Experiences of and attitudes to contraceptive services among a sample of
      attenders at general practices in Dublin.
AB  - The aim of this pilot project, using quantitative and qualitative methods, was to
      gain insights into contraceptive service utilisation by studying the experiences
      and attitudes of a sample of women using general practice for contraception
      services in Dublin.

PMID- 10920295
TI  - Translocation of a copper 7 intra-uterine contraceptive device with subsequent
      penetration of the caecum: case report and review.
AB  - A case of translocated Copper 7 intra-uterine contraceptive device with impending
      caecal penetration is reported and discussed.

PMID- 10920297
TI  - A pre-coital pill? A preliminary in vitro study.
AB  - The use of the progestogen-only pill as a 'pre-coital contraceptive' was tested
      by in vitro studies of sperm-mucus interaction. The results suggest that a single
      tablet of levonorgestrel 30 microg, or norethisterone 350 microg, was effective
      in preventing sperm migration in the cervical mucus about 12 hours later. This
      suggests that the progestogen-only pill may be effective as a 'morning before
      pill'.

PMID- 10920298
TI  - The clinical enquiry service; benign intracranial hypertension.
AB  - Considering how uncommon the condition is (3.3 cases per 100 000 women aged 15 to
      44 years) the CEU has received a surprising number of enquiries about
      contraceptive options for women with a diagnosis of idiopathic benign
      interacranial hypertension.

PMID- 10920299
TI  - The myths of laparoscopic surgery.
AB  - Laparoscopic surgery has been rapidly accepted without rigorous scientific study.
      New procedures and technologies have advanced rapidly, and most gynecologists
      have embraced these techniques. I believe that the new technology has given rise
      to the following myths: (1) that there are associated cost savings, (2) that new
      technology is always better than the old, (3) that a steep learning curve is
      acceptable, (4) that market share will be lost without the new techniques, (5)
      that oncologic surgery is not different when performed laparoscopically, (6) that
      operations are the same with the laparoscope, and (7) that every gynecologist can
      do these procedures. A critical evaluation of new technology and of laparoscopic
      techniques needs to be performed.

PMID- 10920300
TI  - Treatment of uterine fibroid tumors in a nude mouse model using high-intensity
      focused ultrasound.
AB  - OBJECTIVE: The purpose of this study was to investigate the potential efficacy of
      high-intensity focused ultrasound for the treatment of uterine fibroid tumors in
      a nude mouse model. STUDY DESIGN: A total of 60 female athymic nude mice were
      inoculated subcutaneously with 3 to 5 x 10(6) ELT-3 cells, a uterine fibroid
      tumor cell line. Tumor size was monitored with transcutaneous caliper
      measurements. The high-intensity focused ultrasound probe was a concave, single
      element, high-power transducer that operated at a frequency of 3.5 MHz. The
      tumors were treated for 30 to 60 seconds using a high-intensity focused
      ultrasonic intensity of 2000 W/cm(2), depending on the tumor size. RESULTS: A
      single high-intensity focused ultrasonic treatment resulted in an average
      reduction in tumor volume of 91% within 1 month of the treatment. Histologic
      analysis of tumors treated with high-intensity focused ultrasound showed
      coagulation necrosis and nuclear fragmentation of tumor cells. CONCLUSION: High
      intensity focused ultrasound effectively reduced uterine fibroid tumor size in a
      nude mouse model. Further studies are needed to assess the in situ response of
      uterine fibroids to high-intensity focused ultrasonic treatment.

PMID- 10920301
TI  - Premarin-induced increases in coronary and uterine blood flow in nonpregnant
      sheep.
AB  - OBJECTIVE: Menopause is associated with an increased incidence of cardiovascular
      disease among women, and estrogen replacement therapy is thought to reduce the
      risk of coronary artery disease. The mechanism by which this occurs is unclear,
      but coronary arterial endothelial and vascular smooth muscle cells have been
      shown to contain estrogen receptors, and their stimulation appears to increase
      nitric oxide synthesis. One conjugated estrogen preparation (Premarin) is widely
      used in postmenopausal hormone replacement therapy, but little is known about its
      effects on cardiovascular hemodynamics. STUDY DESIGN: This study was designed to
      determine whether Premarin, like 17beta-estradiol, has significant effects on
      cardiac output and coronary and uterine blood flows at doses used clinically
      (0.625, 1.25, and 2.5 mg). Nonpregnant oophorectomized sheep were implanted with
      instruments to measure cardiac output, left coronary (circumflex) artery blood
      flow, uterine blood flow, heart rate, and systemic arterial blood pressure. After
      recovery from surgery, the animals received intravenous bolus injections of
      either 17beta-estradiol (1.0 microg/kg), Premarin (0.625, 1.25, or 2. 5 mg), or
      vehicle on different days. RESULTS: The 1.0-microg/kg dose of 17beta-estradiol
      significantly increased coronary blood flow by 15% +/- 2% from baseline (mean +/-
      SEM). Premarin also increased coronary blood flow significantly at the 1.25- and
      2.5-mg dose levels by 12% +/- 3% and 14% +/- 4%, respectively. As expected 17beta
      estradiol increased uterine blood flow from a baseline of 15 +/- 3 mL/min to 169
      +/- 19 mL/min. Premarin treatment was associated with a significant increase in
      uterine blood flow, which increased from an average baseline of 14 +/- 4 mL/min
      to 46 +/- 10 mL/min, 95 +/- 18 mL/min, and 135 +/- 20 mL/min at the three doses
      tested (0. 625, 1.25, and 2.5 mg, respectively). 17beta-Estradiol also increased
      cardiac output by 12% +/- 3%. Premarin increased cardiac output 2% +/- 3%, 9% +/-
      4%, and 11% +/- 3%, with only the highest dose producing a significant change.
      17beta-Estradiol also increased heart rate by 12% +/- 1%, whereas Premarin at
      doses of 0.625, 1.25, and 2.5 mg increased it by 4% +/- 3%, 7% +/- 4%, and 10% +/
      2%, respectively (increase significant only at the highest dose). Neither 17beta
      estradiol nor Premarin altered either stroke volume or systemic arterial
      pressure. CONCLUSION: Premarin, like 17beta-estradiol, has significant systemic,
      coronary, and uterine vascular effects. These vascular effects may help to
      explain in part why these compounds are cardioprotective.

PMID- 10920302
TI  - Serum antibodies to the 27-kd heat shock protein in women with gynecologic
      cancers.
AB  - OBJECTIVES: Among women the association between heat shock protein immunity and
      cancer has been examined primarily for breast cancer. Autoantibodies to the 27-kd
      heat shock protein were detected in some patients with breast cancer but not in
      control subjects, and the presence of these antibodies was correlated with
      improved survival. We examined the relationship between autoimmunity to heat
      shock proteins and the diagnosis of malignancies of the female genital tract.
      STUDY DESIGN: Serum samples from women seen for possible gynecologic malignancies
      or returning for evaluation after surgery, radiation, chemotherapy, or a
      combination for gynecologic cancers were tested for immunoglobulin G antibodies
      to the 27-kd, 60-kd, 70-kd, and 90-kd heat shock proteins by enzyme-linked
      immunosorbent assay with the purified recombinant proteins bound to wells of a
      microtiter plate. Serum samples from women with no history of malignancies served
      as control preparations. RESULTS: Antibodies to the 27-kd heat shock protein were
      detected in only 1 of 29 healthy control subjects (3.4%) and 1 of 23 women whose
      lesions were benign (4.3%). In marked contrast, 39 of 96 women with gynecologic
      cancers (40.6%) had positive antibody detection (P =.0004 vs benign). The
      percentages of positive results seen for ovarian (17/34, 50%), endometrial
      (13/34, 38.2%), cervical and uterine (3/10, 30%), vaginal and vulvar (3/5, 60%),
      and other (3/13, 23.1%) cancers were not significantly different from each other.
      Similar prevalences of antibodies to the 27-kd heat shock protein were seen among
      patients with cancer who had untreated active disease and after treatment. Unlike
      the results with antibodies to the 27-kd heat shock protein there was no
      relationship between antibodies to the other heat shock proteins and any
      gynecologic cancer. CONCLUSION: Circulating autoantibodies to the 27-kd heat
      shock protein were found to be associated with malignancies of the female genital
      tract.

PMID- 10920303
TI  - In vitro studies of cryoablation of the endometrium.
AB  - OBJECTIVE: The aims of this study were to quantify the tissue damage in vitro of
      a series of freezing protocols with the Endocryo (Spembley Medical Ltd, Andover,
      United Kingdom) cryoprobe for ablation of the endometrium and to determine the
      relative importance of the freezing parameters contributing to the cryolesion.
      STUDY DESIGN: The efficacy and safety of the Endocryo cryoprobe were assessed in
      vitro with 84 different experiments on freshly excised uterine specimens. Tissue
      necrosis was quantified by means of a histochemical technique after incubation of
      the uterine specimens under nearly physiologic conditions. RESULTS: A typical
      lesion was made up of a superficial area of tissue necrosis and a deeper area of
      sublethal damage. Tissue necrosis was >3 mm when the probe was in direct contact
      with the endometrium. Consistent tissue necrosis was only observed with tissue
      temperatures below -30 degrees C. Safe tissue damage was only consistently seen
      after < or =2 minutes of freezing. When the gap between the probe and the
      endometrium was filled with distention medium and was >2 mm, tissue damage was
      insufficient for clinical purposes irrespective of the medium used. CONCLUSION:
      The Endocryo cryoprobe provided a successful means of achieving endometrial
      ablation in vitro. The use of a uterine distention medium appeared to be of
      little value in improving the efficacy of the probe in vitro.

PMID- 10920305
TI  - Adverse behavioral and sexual factors in chronic vulvar disease.
AB  - OBJECTIVE: We investigated the prevalence of adverse sexual, personal hygiene,
      and self-treatment behavior among women with chronic benign vulvar and vaginal
      disorders. STUDY DESIGN: This study was carried out by means of a scientific
      clinical audit producing actuarial data by way of a semistructured questionnaire.
      Subjects consisted of a sample of 530 cases treated at a specialist clinic for
      vulvar diseases. In addition to clinical and laboratory investigations, the
      patients were interviewed by the clinic's psychologist, who used a structured
      interview schedule developed specifically for the study. Descriptive analysis and
      analysis of variance were used to investigate data. RESULTS: Most patients
      remained sexually active in spite of arousal failure and discomfort and engaged
      in unlubricated and often painful sexual intercourse. Most women engaged in
      potentially harmful genital hygiene and self-treatment behavior. Adverse self
      treatment practices but not adverse genital hygiene practices were associated
      with greater symptom duration. CONCLUSIONS: Adverse practices should be addressed
      during the management of cases of chronic vulvar disease.

PMID- 10920304
TI  - Effects of oral contraceptives on vascular endothelium in premenopausal women.
AB  - OBJECTIVE: Premenopausal women are protected against atherosclerosis by high
      plasma estrogen levels, which have been suggested to augment endothelial nitric
      oxide synthesis and to improve endothelial function. In contrast, premenopausal
      use of oral contraceptives is associated with an increased cardiovascular risk.
      We investigated the influence of oral contraception on endothelial function.
      STUDY DESIGN: Sixteen healthy premenopausal women with a mean age (+/-SD) of 27
      +/- 3 years, 8 of whom used oral contraceptives and 8 of whom did not, were
      examined in a case-control study. Forearm plethysmography was used to measure
      changes of forearm blood flow in response to intra-arterial infusion of
      increasing doses of acetylcholine, sodium nitroprusside, and N (G)-monomethyl-L 
      arginine. RESULTS: Endothelium-dependent vasodilatation (change from baseline
      after acetylcholine 48 microg/min) was similar between women with (828% +/- 137%)
      and without oral contraception (701% +/- 114%; P not significant), as was
      endothelium-independent vasodilatation (change from baseline after sodium
      nitroprusside 3200 ng/min, 271% +/- 38% vs 289% +/- 23%; P not significant). In
      contrast, inhibition of nitric oxide synthase with N (G)-monomethyl-L -arginine
      induced a significantly more marked decrease in blood flow among women with oral
      contraception than among those without at all dosages (change from baseline after
      4-micromol/min N (G)-monomethyl-L -arginine, -26% +/- 3% vs -14% +/- 5%; P =.009
      by analysis of variance). CONCLUSION: Stimulated nitric oxide bioavailability
      remained unaffected in a group of premenopausal women receiving oral
      contraceptives. In contrast, basal nitric oxide production and release appeared
      to be enhanced by oral contraceptive use.

PMID- 10920306
TI  - Molecular Papanicolaou tests in the twenty-first century: molecular analyses with
      fluid-based Papanicolaou technology.
AB  - OBJECTIVE: This study was undertaken to demonstrate the feasibility of performing
      molecular analyses at the deoxyribonucleic acid, ribonucleic acid and protein
      levels of cervical cytologic examination with a methanol fluid-based Papanicolaou
      specimen collection system. STUDY DESIGN: Genomic deoxyribonucleic acid and total
      ribonucleic acid were extracted from cell pellets obtained from the residual
      fluid-based Papanicolaou specimen collection buffer after clinical processing.
      Genomic and human papillomavirus deoxyribonucleic acid polymerase chain reaction
      and reverse transcriptase-polymerase chain reaction were performed. Messenger
      ribonucleic acid transcript analysis and human papillomavirus 16 E6 mutational
      analysis were also performed. Methylation-specific polymerase chain reaction was
      used to evaluate hypermethylation status of the p16 gene and the gene for E
      cadherin. Immunohistochemical staining for protein expression was performed on
      the processed monolayer slides. RESULTS: Cell pellets from the residual fluid
      based cytologic specimen yielded good quality deoxyribonucleic acid and
      ribonucleic acid. Molecular analyses of genomic deoxyribonucleic acid were
      successful for the identification of human papillomavirus E6 and p53 polymorphism
      status by means of restriction enzyme digestion and direct sequencing.
      Methylation status of the promotor regions of the p16 tumor suppressor gene and
      the gene for E-cadherin were also successfully identified. Ribonucleic acid was
      used as the template for transcript analysis and mutational analysis of the
      corresponding complementary deoxyribonucleic acid of the p53 gene. Protein
      expression analysis was demonstrated by immunohistochemical staining for
      carcinoembryonic antigen. CONCLUSION: It is feasible to conduct multiple
      molecular analyses at the deoxyribonucleic acid, ribonucleic acid, and protein
      levels of the cervicovaginal cell pellets from the residual fluid-based
      Papanicolaou cytologic specimen. This relatively simple and widely used
      collection system will allow significant advances in molecular epidemiology and
      eventual development of a molecular Papanicolaou test.

PMID- 10920307
TI  - The role of nitric oxide in mediating adenosine-induced increases in uterine
      blood flow in the oophorectomized nonpregnant sheep.
AB  - OBJECTIVE: Adenosine administration to the uterine vasculature of the nonpregnant
      oophorectomized sheep results in dose-related increases in uterine blood flow.
      This study was designed to determine whether these adenosine-induced increases in
      uterine blood flow are mediated in part by nitric oxide release. STUDY DESIGN:
      Five nonpregnant oophorectomized ewes had catheters placed in the femoral artery
      and vein and in the lateral branches of the right and left main uterine arteries.
      Adenosine dissolved in isotonic sodium chloride solution was infused into the
      uterine artery at sequentially increasing doses (1, 3, 10, 30, 100, and 300
      microg/min), and a dose-response curve was constructed. After determination of
      control responses to adenosine a 10-mg/kg dose of the nitric oxide synthase
      inhibitor N omega-nitro-L -arginine methyl ester was administered into the
      femoral vein; the dose-response curves to adenosine were then determined again.
      Responses after N omega-nitro-L -arginine methyl ester administration were
      compared with those obtained before nitric oxide blockade. RESULTS: Adenosine
      increased uterine blood flow in a dose-related fashion, from a baseline of 11 +/-
      2 mL/min to 140 +/- 19 mL/min. No further increase was seen with adenosine doses
      >300 microg/min. There were no significant alterations in systemic arterial
      pressure or heart rate in response to uterine infusion of adenosine. N omega
      nitro-L -arginine methyl ester administration increased baseline blood pressure
      24% +/- 4% and decreased heart rate 13% +/- 4%. Responses to adenosine after N
      omega-nitro-L -arginine methyl ester administration were significantly reduced,
      from a maximum at the highest dose of 140 +/- 19 mL/min to 95 +/- 13 mL/min (P
      <.001). CONCLUSION: A significant portion of adenosine-induced vasodilation in
      the uterine vasculature appears to be mediated by the release of nitric oxide.

PMID- 10920308
TI  - Assessment of 5-aminolevulinic acid-induced porphyrin fluorescence in patients
      with peritoneal endometriosis.
AB  - OBJECTIVE: The purpose of this study was to examine the diagnostic potential for
      patients with endometriosis of porphyrin fluorescence after oral administration
      of 5-aminolevulinic acid. STUDY DESIGN: Fifteen women referred for laparoscopy
      because of suspected endometriosis received 1 or 10 mg/kg 5-aminolevulinic acid
      orally. After 1.5 to 6 hours endoscopic fluorescence spectral analysis and video
      inspection were performed. RESULTS: With 10 mg/kg 5-aminolevulinic acid and
      application intervals of >3 hours we observed a significantly higher porphyrin
      fluorescence in active peritoneal endometriosis than in adjacent normal
      peritoneum. Pigmented and nodular endometriosis showed weak to negative
      fluorescence. A strong fluorescence of the fimbrial mucosa was seen. A 1-mg/kg
      dose of 5-aminolevulinic acid was insufficient for fluorescence diagnosis. No
      side effects were recorded. CONCLUSION: Porphyrin fluorescence after oral
      administration of 5-aminolevulinic acid may be beneficial in diagnosis of
      peritoneal endometriosis. The strong fluorescence of fimbrial mucosa may limit
      the applicability of this technique in young women, however, because phototoxic
      damage cannot be excluded at present.

PMID- 10920309
TI  - Increase in serum leptin concentrations among women with endometriosis during
      danazol and leuprolide depot treatments.
AB  - OBJECTIVE: This study was undertaken to evaluate serum leptin concentrations in
      women with endometriosis during treatment with danazol and with leuprolide depot.
      STUDY DESIGN: Twenty patients aged 18 to 42 years with regular menses and
      documented pelvic endometriosis were recruited from a university hospital
      setting. Treatment was 200 mg danazol 3 times daily for 6 months or 3.75 mg
      leuprolide depot every 28 days for 6 months. Serum leptin concentrations were
      measured before, during, and after treatment. A single blood sample was taken
      from each of 10 control women without endometriosis for comparison. Serum leptin
      level was measured with a radioimmunoassay kit with human leptin, and analysis of
      variance and paired t tests were used for statistical analysis. RESULTS: Serum
      leptin levels were almost the same among women with endometriosis as in the
      control group. Leptin levels were higher among women with endometriosis during
      treatment with danazol and leuprolide(P <.001). Three months after treatment,
      leptin values remained moderately higher than before treatment. CONCLUSION:
      Danazol and leuprolide increased serum leptin levels. The mechanism of leptin
      increase is unclear. Further studies are needed to determine whether an
      adipogonadal axis exists.

PMID- 10920310
TI  - Twin birth weight discordance and risk of preterm birth.
AB  - OBJECTIVES: Our purpose was to determine whether birth weight discordance is a
      risk factor for preterm birth of twins, and to further characterize the
      relationships involved. STUDY DESIGN: Maternally linked 1978-1990 Missouri birth
      certificates were used to analyze gestations resulting in live twins. We used
      contingency tables and multiple logistic regression. RESULTS: The degree of
      discordance correlated strongly with risk for live preterm birth but only for
      discordances >30% and preterm birth at <32 weeks' gestation. Among 9479
      pregnancies with discordance <30%, 9.5% ended in birth at <32 weeks' gestation,
      versus 13.7% of 326 with discordance of 30% to 40% (P =.03) and versus 34.1% of
      126 with discordance > or =40% (P <. 001). There were 42 preterm twin births at
      <32 weeks' gestation with discordances > or =40%. Of these, 51% were attributable
      to fetal growth restriction and 16% to large size for gestational age in one
      infant; in 72% the smaller twin was the second born, and in 86% the twins were
      like sex. The relative association between > or =40% discordance and preterm
      birth at <32 weeks' gestation was strengthened (final odds ratio, 9.54; P <.0001)
      in a multivariate model containing other risk factors for delivery at <32 weeks'
      gestation: black race, either twin small for gestational age, unmarried, teenage
      mother, number of male fetuses, like fetal sex, education <12 years, nulliparity,
      and cigarette smoking. CONCLUSIONS: Twin birth weight discordance has now clearly
      been demonstrated to be a risk factor for preterm birth. The effect was found
      particularly with discordances > or =40% before 32 weeks' gestation. Discordance
      was usually attributable to fetal growth restriction, most often in the second
      born twin.

PMID- 10920311
TI  - Effect of stimulatory and inhibitory drugs on uterine electrical activity
      measured noninvasively from the abdominal surface of pregnant rats.
AB  - OBJECTIVE: Our purposes were (1) to identify and analyze parameters of uterine
      electrical activity that change during active term and preterm labor in response
      to stimulatory (oxytocin) or inhibitory (terbutaline) agents and (2) to correlate
      the information obtained from abdominal surface measurement of electrical
      activity with intrauterine pressure and with the electrical activity measured
      directly from the uterine surface in vivo. STUDY DESIGN: Electromyographic
      activity was acquired simultaneously from the uterine wall and the abdominal
      surface by means of unipolar electrodes. Electromyographic activity was recorded
      in the 0.3 to 50-Hz range and digitized at 200 samples per second. Intrauterine
      pressure was measured via an intrauterine catheter. The effect of cumulative
      doses of oxytocin and terbutaline on power density spectrum, amplitude, number
      and duration of electromyographic bursts, and intrauterine pressure was recorded
      in anesthetized rats during spontaneous active term labor (n = 7) and induced
      preterm labor (n = 6). RESULTS: Bursts of electromyographic activity recorded
      from the abdominal surface mirrored those from the uterine wall, albeit at a
      lower amplitude. During active term labor, lower concentrations of oxytocin did
      not significantly affect power-density-spectrum energy, amplitude, or number of
      bursts per unit time. The duration of electromyographic bursts increased dose
      dependently. Myometrial contractions were phasic, with return to the baseline
      between phases. As the concentration of oxytocin increased, the energy,
      amplitude, and number of bursts per unit time declined while the intrauterine
      pressure continued to rise until the contraction became tetanic, without return
      to the baseline. In rats with induced preterm labor, terbutaline inhibited
      uterine contractility by decreasing the intrauterine pressure. This was
      accompanied by a progressive decrease in the power density spectrum, amplitude,
      number, and duration of the uterine wall and abdominal surface electrical bursts.
      CONCLUSIONS: First, uterine electromyographic activity measured noninvasively
      from the abdominal surface reflects changes in uterine electrical activity and
      intrauterine pressure measured directly and invasively in term and preterm labor,
      as well as during treatments to stimulate or inhibit labor. Second, this
      noninvasive method may be useful in monitoring uterine activity in vivo. Third,
      clinical studies to evaluate this technology in human subjects are warranted.

PMID- 10920312
TI  - Influence of oxytocin on prostaglandin E2, intracellular calcium, and cyclic
      adenosine monophosphate in human amnion-derived (WISH) cells.
AB  - OBJECTIVE: This study was undertaken to investigate the regulation of
      prostaglandin release by oxytocin and the influence of oxytocin on intracellular
      calcium and on the cyclic adenosine monophosphate system in human amnion-derived
      WISH cells. STUDY DESIGN: We determined prostaglandin E(2) release from WISH
      cells treated with oxytocin, evaluated the cytosolic calcium concentration in
      single WISH cells by confocal microscopy, and measured both intracellular cyclic
      adenosine monophosphate levels and adenylyl cyclase activity after oxytocin
      treatment. RESULTS: Treatment of WISH cells with oxytocin resulted in a
      concentration-dependent release of prostaglandin E(2), which was increased by
      lithium chloride and inhibited by indomethacin and U-73122. In single WISH cells,
      oxytocin increased cytosolic calcium. Moreover, the hormone lowered levels of
      intracellular cyclic adenosine monophosphate but did not alter adenylyl cyclase
      activity. CONCLUSIONS: Our data demonstrate, for the first time, that WISH cells
      respond to oxytocin by increasing prostaglandin E(2) release. In addition to
      phospholipase C activation and cytosolic calcium increase, the hormone effect
      involves also a reduction of the cyclic adenosine monophosphate level.

PMID- 10920313
TI  - Postpartum stroke: a twenty-year experience.
AB  - OBJECTIVE: The aim of this study was to characterize the clinical presentation,
      etiology, and acute and subsequent outcomes of postpartum stroke. STUDY DESIGN:
      This 20-year, single-center, retrospective review included 20 women without
      previous neurologic deficit with clinical and neuroimaging diagnoses of
      postpartum stroke. RESULTS: Eight of 20 women (40%) were delivered abdominally.
      Conduction anesthesia was induced in 9 of 20 women (45%). Causes of stroke
      included cerebral infarction (n = 13; 7 venous, 6 arterial), intracerebral
      hemorrhage (n = 5; 1 cocaine-induced, 1 anatomic malformation), cerebritis (n =
      1), and cerebral atrophy (n = 1). The median time at onset of stroke was 8 days
      post partum (range, 3-35 days). Headache, seizures, visual change, and
      hemiparesis were the most common presenting findings but were neither specific to
      the underlying pathologic condition nor predictive of ultimate maternal outcome.
      There were 2 maternal deaths, both caused by severe intracerebral hemorrhage.
      Intracerebral hemorrhage was associated with the poorest outcome (2 deaths and 1
      residual neurologic deficit). Eight women had residual neurologic deficit. There
      was no correlation between a trial of labor (P =.4; odds ratio, 0.4; 95%
      confidence interval, 0.01-6.5) or vaginal versus cesarean mode of delivery (P
      =.6; odds ratio, 1.3; 95% confidence interval 0.1-16.8) and ultimate neurologic
      diagnosis (cerebral infarction or intracerebral hemorrhage). However, the
      incidence of cesarean delivery was greater in the cohort of women with postpartum
      stroke than in the overall obstetric population (P =.015; odds ratio, 3.2; 95%
      confidence interval, 1.2-8.5). One of the 20 women received methergine; 1
      received bromocriptine. All women were either normotensive or had well-controlled
      hypertension at postpartum discharge. New-onset hypertension or exacerbation of
      existing hypertension occurred after the acute neurologic insult; subsequent mean
      (+/-SD) arterial blood pressure was 128.9 +/- 24.0 mm Hg. CONCLUSION: Postpartum
      stroke is a multifactorial, uncommon, and nonpreventable complication of
      pregnancy. There was an association between postpartum stroke and hypertensive
      disorders of pregnancy and cesarean delivery. However, this study refutes any
      etiologic association between conduction anesthesia and postpartum stroke.

PMID- 10920314
TI  - Suppression by developing ovarian follicles of the low-dose endotoxin-induced
      glomerular inflammatory reaction in the pregnant rat.
AB  - OBJECTIVE: In the current study the role of developing ovarian follicles in the
      control of the endotoxin-induced pregnancy-specific inflammatory reaction was
      evaluated. STUDY DESIGN: Follicular development was induced in pregnant rats (n =
      20) by means of daily intraperitoneal injections of follicle-stimulating hormone
      from day 11 of pregnancy until the end of the experiment. Control pregnant rats
      (n = 20) received daily sodium chloride injections. All pregnant rats were
      infused for 1 hour with either 2 mL endotoxin solution (1.0 microg/kg body
      weight) or 2 mL sodium chloride solution on day 14 and killed 4 hours or 3 days
      later. At death, the left kidneys were snap-frozen and immunohistologically
      stained for the presence of polymorphonuclear leukocytes and monocytes. RESULTS:
      The results show that in control pregnant rats endotoxin significantly increased
      glomerular polymorphonuclear leukocyte and monocyte numbers at both 4 hours and 3
      days after endotoxin infusion. Induction of follicular development did not affect
      glomerular polymorphonuclear leukocyte number after endotoxin infusion but
      significantly decreased the number of monocytes in the glomeruli at both 4 hours
      and 3 days after endotoxin infusion. CONCLUSION: We conclude that follicles
      stimulated with follicle-stimulating hormone produce a follicular factor or
      factors that are able to prevent the endotoxin-induced influx of monocytes into
      the glomeruli of pregnant rats. It is suggested that these factors play a role in
      the control of inflammatory processes associated with reproduction, including the
      disease of pregnancy, preeclampsia.

PMID- 10920315
TI  - Human neutrophil collagenase (matrix metalloproteinase 8) in parturition,
      premature rupture of the membranes, and intrauterine infection.
AB  - OBJECTIVES: The mechanisms by which microbial invasion of the amniotic cavity
      leads to membrane weakening and rupture are poorly understood. Recently,
      endogenous host enzymes have been implicated in this process. Matrix
      metalloproteinases are a family of potent enzymes that degrade components of the
      extracellular matrix. Collagen type I provides the main tensile strength of the
      fetal membranes. Matrix metalloproteinase 8 (MMP-8), or neutrophil collagenase,
      degrades interstitial collagens, acting preferentially on collagen type I. This
      study was undertaken (1) to determine whether MMP-8 is present in amniotic fluid
      and whether its concentrations are changed in preterm and term labor and membrane
      rupture with and without intra-amniotic infection and (2) to determine whether
      the amniotic fluid concentrations of MMP-8 in labor at term are different in the
      lower and upper uterine compartments. STUDY DESIGN: A cross-sectional study was
      conducted and transabdominal amniocentesis was performed in women in the
      following categories: (1) midtrimester (n = 25), (2) preterm labor in the
      presence and absence of microbial invasion of the amniotic cavity (n = 86), (3)
      preterm premature rupture of the membranes in the presence and absence of
      microbial invasion of the amniotic cavity (n = 51), (4) term patients in labor
      and not in labor (n = 51), and (5) term premature rupture of membranes (n = 20).
      Additional paired samples of amniotic fluid were retrieved by transabdominal
      amniocentesis (upper compartment) and transvaginal amniocentesis (lower or
      forebag compartment) from 14 term patients (28 samples) in spontaneous labor with
      intact membranes. Amniotic fluid MMP-8 concentrations were determined with a
      sensitive and specific immunoassay. RESULTS: MMP-8 was detected in 95.4%
      (249/261) of all samples. (1) Spontaneous human parturition was associated with a
      significant increase in amniotic fluid concentrations of MMP-8 in both term and
      preterm gestation. Term (no labor median, 3.3 ng/mL; range, <0.06-38.6 ng/mL; vs
      labor median, 16.6 ng/mL; range, 0. 33-1650 ng/mL; P <.05). Patients with preterm
      labor who delivered preterm (in the absence of microbial invasion of the amniotic
      cavity) had a significantly higher median amniotic fluid MMP-8 concentration than
      those with preterm labor who delivered at term (preterm labor, term delivery
      median, 3.1 ng/mL; range, <0.06-415.1 ng/mL; vs preterm labor, preterm delivery
      median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL;P <.003). (2) Spontaneous rupture
      of membranes in preterm gestation but not in term gestation was associated with
      elevated amniotic fluid concentrations of MMP-8. Preterm gestation (preterm
      labor, intact membranes median, 3.1 ng/mL; range, <0.06-415. 1 ng/mL; vs preterm
      premature rupture of membranes median, 35.1 ng/mL; range, 0.71-1184.1 ng/mL; P
      <.05). Term gestation (intact membranes median, 3.3 ng/mL; range, 0.24-38.6
      ng/mL; vs rupture of membranes median, 5.6 ng/mL; range, 0.22-19.8 ng/mL; P =.9).
      (3) Microbial invasion of the amniotic cavity was associated with a significant
      increase in amniotic fluid MMP-8 concentration in patients with preterm labor and
      intact membranes, as well as in patients with preterm premature rupture of
      membranes. Preterm labor (no microbial invasion of the amniotic cavity, preterm
      delivery median, 32.5 ng/mL; range, <0.06-6006.6 ng/mL; vs microbial invasion of
      the amniotic cavity median, 208.1 ng/mL; range, 4.2-14,600 ng/mL; P <.001).
      Preterm premature rupture of membranes (no microbial invasion of the amniotic
      cavity median, 35.1 ng/mL; range, 0.71-1184. 1 ng/mL; vs microbial invasion of
      the amniotic cavity median, 317.9 ng/mL; range, 2.16-14,500 ng/mL; P <.01). (4)
      The median amniotic fluid MMP-8 concentrations were significantly higher in fluid
      obtained from the forebag compartment than in that obtained from the upper
      compartment (median, 66.2 ng/mL; range, 7.4-170 ng/mL; vs median, 13.3 ng/mL;
      range, 2-170 ng/mL; respectively; P <.01). (ABSTRACT TRUNCATED)

PMID- 10920316
TI  - Complications according to mode of delivery among human immunodeficiency virus
      infected women with CD4 lymphocyte counts of < or = 500/microL.
AB  - OBJECTIVE: We sought to describe rates of and risk factors for complications by
      delivery mode among human immunodeficiency virus-infected women with CD4 counts
      of < or = 500/microL. STUDY DESIGN: Complication rates were calculated by
      delivery mode, as follows: planned cesarean delivery performed without labor or
      rupture of membranes, other cesarean delivery performed after labor or rupture of
      membranes, or vaginal delivery. Risk factors were evaluated. RESULTS: Major
      complications in the planned cesarean delivery (n = 37), other cesarean delivery
      (n = 95), and vaginal delivery (n = 365) groups were amnionitis or endometritis
      (16%, 27%, and 7%, respectively), wound infection (5%, 8%, and <1%,
      respectively), and transfusion (8%, 6%, and 3%, respectively). Any peripartum
      infection occurred among 16 (18%) of those with a CD4 count of <200/microL and 43
      (13%) with a CD4 count of > or =200/microL (P =.17). On multivariate analyses,
      factors associated with amnionitis-endometritis were cesarean delivery and
      African American race, and a factor associated with transfusion was third
      trimester anemia. CONCLUSION: Endometritis and wound infection occurred more
      frequently among human immunodeficiency virus-infected women after cesarean than
      among women undergoing vaginal delivery; however, complication rates overall were
      within the range reported in human immunodeficiency virus-negative women.
      Measures to decrease complications in human immunodeficiency virus-infected
      women, such as greater use of prophylactic antibiotics, should be assessed.

PMID- 10920317
TI  - Secretory component: a potential regulator of endometrial-decidual prostaglandin
      production in early human pregnancy.
AB  - OBJECTIVE: We sought to investigate the production of secretory component, an
      inhibitor of phospholipase A(2), and prostaglandins by human endometrium-decidua.
      STUDY DESIGN: The production of secretory component and prostaglandins by
      explants and dispersed glandular and stromal cells of secretory endometrium and
      first-trimester and term decidua were measured by enzyme-linked immunosorbent
      assay and radioimmunoassay, respectively. RESULTS: Explants of first-trimester
      decidua produced significantly more secretory component and less prostaglandins
      than secretory endometrium. Immunohistochemical studies localized secretory
      component to epithelial glandular cells. At term, when fewer glandular cells are
      present, both secretory component and prostaglandin production were low. Exposure
      of first-trimester decidua to progesterone significantly increased secretory
      component production. CONCLUSION: Secretory component and prostaglandins localize
      primarily to epithelial glandular cells in endometrium-decidua, and their
      production appears to be inversely correlated. The increase in secretory
      component by first-trimester decidua after progesterone stimulation may account
      for the down-regulation of endometrial prostaglandin synthesis after
      implantation, a process thought to be necessary for pregnancy success.

PMID- 10920319
TI  - Cyclooxygenase is involved in the effects of progesterone-induced blocking factor
      on the production of interleukin 12.
AB  - OBJECTIVE: Immunologic effects of progesterone are mediated by the progesterone
      induced blocking factor. Progesterone-induced blocking factor inhibits natural
      killer cytotoxic activity and arachidonic acid release from mononuclear cells.
      The relationship between increased prostaglandin synthesis and increased
      cytotoxic activity of the lymphocytes is still unclear; therefore we investigated
      the effect of progesterone-induced blocking factor-neutralizing antibody, as well
      as simultaneous indomethacin treatment, on interleukin 12 production. STUDY
      DESIGN: Pregnancy lymphocytes were treated with anti-progesterone-induced
      blocking factor antibody or lipopolysaccharide as a positive control in the
      presence or absence of indomethacin. Interleukin 12 production by peripheral
      blood mononuclear cells was detected by immunocytochemical examination. The 2
      tailed Student t test was used for statistical evaluation. RESULTS:
      Neutralization of progesterone-induced blocking factor, as well as
      lipopolysaccharide treatment, resulted in an increased expression of interleukin
      12 that was corrected by simultaneous indomethacin treatment. CONCLUSION:
      Progesterone-induced blocking factor reduces the expression of interleukin 12 via
      the inhibition of arachidonic acid metabolism. This results in lowered cytotoxic
      natural killer activity, which favors a normal pregnancy outcome.

PMID- 10920318
TI  - Modulation of rat uterine contractility by mast cells and their mediators.
AB  - OBJECTIVE: This study was designed to test the possibility that mast cells play a
      role in the regulation of uterine contractility. STUDY DESIGN: Histamine and rat
      mast cell protease II levels were determined by radioenzymatic assay and standard
      radial immunodiffusion techniques, respectively, in uterine tissues from Wistar
      rats with timed pregnancies. Isolated uterine strips from nonsensitized and
      ovalbumin-sensitized nonpregnant and pregnant Wistar rats were used for isometric
      tension recording. Contractile responses to compound 48/80, carbachol, ovalbumin,
      normal rabbit serum, antirat immunoglobulin E, and 5-hydroxytryptamine were
      obtained. Antagonists methysergide, ketanserin, 5,8,11, 14-eicosatetraynoic acid,
      diphenhydramine, and sodium meclofenamate were also used. RESULTS: Tissue levels
      of rat mast cell protease II and histamine were decreased during delivery
      compared with prepartum and postpartum levels. Carbachol and compound 48/80
      stimulated uterine contractility, and responses were highest during late
      gestation (day 16 to term). Responses to ovalbumin of uterine tissues in rats
      sensitized to the antigen were highest at midpregnancy and decreased during the
      last 10 days of gestation. Ovalbumin challenge in vitro increased the frequency
      and magnitude of contractions in tissues from ovalbumin-sensitized rats. Compound
      48/80 and antirat immunoglobulin E stimulated contractility in both control and
      sensitized rats. None of the antagonists prevented the contractile responses.
      CONCLUSIONS: Activation of mast cells is an effective mechanism for stimulation
      of uterine contractility and may play an important role in the control of term
      and preterm parturition.

PMID- 10920320
TI  - An appraisal of treatment guidelines for antepartum community-acquired pneumonia.
AB  - OBJECTIVE: The optimal strategy for the initial evaluation and management,
      including criteria for hospitalization, of pregnant women with pneumonia has not
      been defined. Our purpose was to evaluate a treatment protocol for antepartum
      pneumonia and to identify criteria for selection of women for potential
      outpatient treatment. STUDY DESIGN: A protocol based on British and American
      Thoracic Society guidelines was introduced and included prompt hospitalization
      and empiric initiation of erythromycin therapy. Maternal and neonatal outcomes
      were analyzed to assess the efficacy of the protocol. A second analysis involved
      the retrospective application of published guidelines to ascertain for which
      women outpatient management might have been appropriate. RESULTS: There were no
      maternal deaths among the 133 women studied, and in 14 (10%) women there was a
      misdiagnosis at admission. Erythromycin monotherapy was judged adequate in all
      but one of the 99 women so treated. Using a modified version of the American
      Thoracic Society guidelines, we project that only 25% of the women hospitalized
      with pneumonia could have been managed safely as outpatients. CONCLUSION: Most
      pregnant women with pneumonia respond well to monotherapy with erythromycin.
      Outpatient management may be a reasonable option for selected women.

PMID- 10920321
TI  - The relationship of smoking, preeclampsia, and secretory component.
AB  - OBJECTIVE: We sought to determine whether total secretory component in serum is
      increased in women in whom preeclampsia subsequently develops. STUDY DESIGN:
      Serum samples were collected serially throughout pregnancy and post partum from
      nulliparous women (N = 1496). Serum concentrations of total secretory component
      were measured by an enzyme-linked immunosorbent assay in all women in whom
      preeclampsia developed (n = 71) and a randomly selected group of normotensive
      women (n = 83). RESULTS: Secretory component increased with smoking (P =.0003)
      and with gestation (P =.0001). In the whole group secretory component was not
      different in women with preeclampsia (P =.10), but there was a significant
      interaction of smoking, gravidity, and preeclampsia (P =.04). Among the women who
      smoked, secretory component was lower in women in whom preeclampsia subsequently
      developed compared with those who remained normotensive (P =.02). This difference
      was significant from 15 to 19 weeks' gestation. CONCLUSION: Very high serum
      concentrations of secretory component in smokers may protect against the
      development of preeclampsia and may indicate the involvement of mucosal
      tolerance.

PMID- 10920322
TI  - Relationship of systemic hemodynamics, left ventricular structure and function,
      and plasma natriuretic peptide concentrations during pregnancy complicated by
      preeclampsia.
AB  - OBJECTIVE: This study was done to evaluate left ventricular structure and
      function among pregnant patients with preeclampsia and compare them with those of
      normotensive pregnant and nonpregnant subjects. It also tested the hypothesis
      that abnormalities in left ventricular structure and function are associated with
      elevated plasma levels of natriuretic peptides. STUDY DESIGN: The study compared
      75 pregnant women (n = 40 with preeclampsia; n = 35 normotensive pregnant women)
      and 10 nonpregnant normotensive control subjects undergoing an echocardiographic
      and biohumoral (renin activity and aldosterone, atrial natriuretic peptide, and
      brain natriuretic peptide concentrations) evaluation. The statistical analysis
      was carried out by analysis of variance, and significance was set at P <.05.
      RESULTS: Comparison of pregnant patients with preeclampsia versus both
      normotensive pregnant women and nonpregnant women showed significant increases in
      left ventricular mass and left ventricular endsystolic and end-diastolic volumes
      and significant reductions in left ventricular ejection fraction and percentage
      of fractional shortening. These changes coincided with increases in plasma levels
      of atrial natriuretic peptide and brain natriuretic peptide that were linearly
      related to the left ventricular structural and functional changes observed in
      patients with preeclampsia. CONCLUSION: Pregnant patients with preeclampsia
      showed adaptation to the increase in systemic blood pressure, with significant
      modification of left ventricular structure and function related to the plasma
      levels of both atrial natriuretic peptide and brain natriuretic peptide. A simple
      evaluation of plasma natriuretic peptide concentrations could help to
      discriminate patients with preeclampsia who have a condition of mild left
      ventricular overload.

PMID- 10920323
TI  - Association of preeclampsia with high birth weight for age.
AB  - OBJECTIVE: The purpose of this study was to examine the effect of gestational
      hypertension and preeclampsia on fetal growth. STUDY DESIGN: A retrospective
      cohort study was conducted on the basis of 97,270 pregnancies delivered between
      1991 and 1996 in 35 hospitals in northern and central Alberta, Canada. Univariate
      and multivariate logistic analyses were performed to examine the impact of
      preeclampsia and gestational hypertension on high-birth-weight (> or =4200 g),
      large-for-gestational-age, low-birth-weight (<2500 g), and small-for-gestational
      age babies. RESULTS: The rate of high-birth-weight fetuses in women with
      gestational hypertension (7. 3%) was higher than in those with normal blood
      pressure (5.6%). After we controlled for confounders, the adjusted odds ratio of
      high birth weight was 1.44 (95% confidence interval, 1.21-1.70) in women with
      gestational hypertension. Preeclampsia was also associated with a statistically
      nonsignificant (P =.054) increased risk of high birth weight (adjusted odds
      ratio, 1.40; 95% confidence interval 0. 99-1.98). The rate of large-for
      gestational-age babies was significantly higher in women with gestational
      hypertension (4.5%) and preeclampsia (4.7%) than in those with normal blood
      pressure (2. 2%), with adjusted odds ratios of 1.50 (95% confidence interval, 1.
      22-1.85) for gestational hypertension and 1.87 (95% confidence interval, 1.31
      2.67) for preeclampsia. Concurrently, women who had gestational hypertension were
      also at higher risk of having low-birth-weight (adjusted odds ratio, 2.4; 95%
      confidence interval, 2.13-2.93) and small-for-gestational-age (adjusted odds
      ratio, 2.04; 95% confidence interval, 1.68-2.48) babies. Women with preeclampsia
      were also at markedly higher risk of having low-birth-weight (adjusted odds
      ratio, 4.14; 95% confidence interval, 3.32-5.15) and small-for-gestational-age
      (adjusted odds ratio, 2.56; 95% confidence interval, 1.92-3.41) babies.
      CONCLUSIONS: There is a significant association of preeclampsia and gestational
      hypertension with large-for-gestational-age infants, in addition to a significant
      association with low-birth-weight and small-for-gestational-age infants. This
      study challenges the currently held belief that reduced uteroplacental perfusion
      is the unique pathophysiologic process in preeclampsia.

PMID- 10920324
TI  - Myometrial contractile strain at uteroplacental separation during parturition.
AB  - OBJECTIVE: A simplified geometric model of the uterine wall during the second and
      third stages of labor was created to estimate the magnitude of myometrial strain
      associated with the initiation of placental separation. STUDY DESIGN: The uterine
      wall was modeled as an isovolumetric, incompressible spherical shell whose
      overall radius decreased and mural thickness increased on uterine muscle
      contraction after delivery of the fetus. Either a 3.5-MHz or a 5-MHz
      ultrasonography probe was used to measure the change in uterine mural thickness
      of 14 healthy patients from just before delivery to the time of initial
      separation of the placenta. The measured change in uterine wall thickness was
      then used to calculate its average radial and circumferential strain with a
      simple mathematic model. RESULTS: Placental separation occurred at radial and
      circumferential strains (mean +/- SD) of 450% +/- 182% and -75% +/- 11%,
      respectively. These strains are consistent with the known maximal contractile
      strains achievable by smooth muscle. CONCLUSION: Placental separation is likely
      associated with maximal myometrial contractile strain. Before birth the presence
      of the fetal and amniotic fluid volumes usually renders such contractile strains
      unachievable, thereby helping to guard against premature placental separation.

PMID- 10920325
TI  - Preeclampsia: evidence for impaired shear stress-mediated nitric oxide release in
      uterine circulation.
AB  - OBJECTIVE: We sought to compare flow-mediated dilatation and myogenic and
      norepinephrine-induced tone in myometrial resistance arteries from women with
      preeclampsia and healthy pregnant women and to evaluate the role that nitric
      oxide may play in these responses. STUDY DESIGN: Arteries (approximately 200
      microm, at 50 mm Hg) were dissected from myometrial biopsy specimens from women
      undergoing emergency cesarean delivery because of preeclampsia (n = 6) and from
      healthy control subjects undergoing planned cesarean delivery (n = 9). Responses
      to intraluminal flow, pressure, and a constrictor agonist (norepinephrine, 10(-6)
      mol/L) were studied in the absence and presence of the nitric oxide synthase
      inhibitor N omeganitro-L -arginine (10(-4) mol/L). Myogenic and norepinephrine
      induced tone were calculated after the determination of artery diameter in the
      absence of extracellular calcium and in the presence of papaverine (10(-4)
      mol/L). RESULTS: An increase in intraluminal flow led to dilatation of isolated
      myometrial arteries from healthy gravid women, whereas flow-mediated dilatation
      was absent in arteries from gravid patients with preeclampsia (increase in
      diameter at maximum flow rate of 204 microL/min, 28% +/- 5% in healthy gravid
      patients vs -15% +/- 6% in gravid women with preeclampsia; analysis of variance,
      P <.05). Addition of N omega-nitro-L -arginine had no significant effect on flow
      mediated responses in arteries from women with preeclampsia, whereas flow
      mediated dilatation was abolished after addition of N omega-nitro-L -arginine in
      arteries from healthy gravid women (increase in diameter at a maximum flow rate
      of 204 microL/min, 28% +/- 5% control vs -9% +/- 5% N omega-nitro-L -arginine;
      analysis of variance, P <.05). Arteries from women with preeclampsia developed
      pressure-induced myogenic and norepinephrine-induced tone, similar to that
      obtained in arteries from healthy gravid women. In arteries from gravid women
      with preeclampsia, inhibition of nitric oxide synthase enhanced myogenic-induced
      tone (25% +/- 4% control vs 35% +/- 5% N omega-nitro-L -arginine; P <.05) and
      norepinephrine-induced tone (36% +/- 4% control vs 46% +/- 6% N omega-nitro-L 
      arginine; P <.05), as in arteries from healthy gravid women. CONCLUSIONS: Nitric
      oxide may participate in modulation of pressure- and norepinephrine-induced tone
      even in preeclampsia, but the shear stress-mediated release of nitric oxide is
      absent. Failure of shear stress-mediated dilation in myometrial arteries from
      gravid women with preeclampsia might contribute to the impaired uteroplacental
      blood flow in this disease.

PMID- 10920326
TI  - Portal vein blood flow-effects of pregnancy, gravity, and exercise.
AB  - OBJECTIVE: We sought to test the hypotheses that pregnancy increases portal vein
      blood flow and that regular exercise training during pregnancy limits the flow
      redistribution away from the splanchnic and uterine circulations in response to
      either gravitational or exercise-induced hemodynamic stress. STUDY DESIGN: Portal
      vein blood flow, which probably reflects changes in uterine blood flow, was
      estimated with ultrasonography in 6 regularly exercising and 6 physically active
      control subjects before and during pregnancy after 15 minutes of rest in the left
      lateral recumbent position, after 5 minutes of standing rest, and immediately and
      5 minutes after 20 minutes of treadmill exercise at 55% +/- 3% of maximal aerobic
      capacity. RESULTS: Portal vein blood flow rose significantly during early and mid
      pregnancy at recumbent rest (from 660 +/- 110 to 1090 +/- 120 mL/min), standing
      rest (580 +/- 70 to 790 +/- 120 mL/min), immediately after exercise (160 +/- 30
      to 360 +/- 60 mL/min), and at 5 minutes of recovery (520 +/- 60 to 760 +/- 110
      mL/min). Before pregnancy, exercise training did not blunt the decremental
      effects of either gravity or exercise on portal vein blood flow. During mid and
      late pregnancy, exercise training had no effect on the fall in portal vein blood
      flow with gravitational stress, but it markedly reduced the decremental effects
      of exercise (average for the 2 time points, -510 +/- 80 vs -840 +/- 100 mL/min)
      and improved recovery at 5 minutes after exercise (940 +/- 140 vs 600 +/- 130
      mL/min). CONCLUSIONS: Portal vein blood flow rises significantly during
      pregnancy, and flow redistribution away from the splanchnic and uterine
      circulations in response to severe hemodynamic stress is reduced by exercise
      training in mid and late pregnancy.

PMID- 10920327
TI  - Indomethacin blocks interleukin 1beta-induced myometrial contractions in pregnant
      rhesus monkeys.
AB  - OBJECTIVE: We sought to determine whether blockade of prostaglandin synthesis
      with indomethacin prevents interleukin 1beta-induced increases in uterine
      contractions in a nonhuman primate model. STUDY DESIGN: Maternal and fetal
      vascular catheters, intra-amniotic fluid pressure catheters, and fetal
      electrocardiographic and myometrial electromyographic electrodes were implanted
      in 11 rhesus monkeys at 124 +/- 2 days' gestation (term, 167 days). After
      postsurgical stabilization (136 +/- 2 days) indomethacin 50 mg was administered
      orally twice daily for 5 days (n = 6). On day 3 human recombinant interleukin
      1beta 10 microg was infused into the amniotic cavity over 2 hours. Five days
      after the last indomethacin dose the study was repeated without indomethacin
      treatment. Uterine activity was continuously monitored and quantified as the
      hourly contraction area (millimeters of mercury. seconds per hour) in the
      experimental group and a control group (n = 5) that received interleukin 1beta
      alone. At timed intervals amniotic fluid was sampled for leukocyte counts and
      assayed for prostaglandin E(2) and F(2alpha), the inflammatory cytokines
      interleukin 1beta, interleukin 6, interleukin 8, tumor necrosis factor alpha, and
      interleukin 1 receptor antagonist by specific assays. RESULTS: Uterine activity
      was increased severalfold from baseline after interleukin 1beta infusion alone
      and in the absence of indomethacin treatment (P <.05). There was no increase in
      uterine contractility when interleukin 1beta was infused concurrently with
      indomethacin treatment. Concentrations of amniotic fluid leukocytes and cytokines
      increased significantly after interleukin 1beta infusion in both the presence and
      absence of indomethacin. Amniotic fluid prostaglandins E(2) and F(2alpha) were
      suppressed during indomethacin treatment but rose significantly after interleukin
      1beta infusion in the absence of indomethacin. Except for higher interleukin 6,
      cytokine levels were unaltered by indomethacin. CONCLUSIONS: After interleukin
      1beta infusion, indomethacin blocked the development of uterine activity.
      Amniotic fluid prostaglandins were suppressed by indomethacin treatment, but
      cytokines and leukocytes were not. These results suggest that prostaglandins or
      possibly other indomethacin-suppressible compounds stimulate uterine activity
      after interleukin 1beta infusion in late-gestation rhesus monkeys or that
      indomethacin has direct tocolytic effects.

PMID- 10920328
TI  - Comparison of infrared spectroscopic and fluorescence depolarization assays for
      fetal lung maturity.
AB  - OBJECTIVE: Infrared spectroscopic analysis of amniotic fluid was recently shown
      to be a potential useful method for the determination of fetal lung maturity.
      Those studies used thin-layer chromatography as a reference method for the
      calibration of the infrared-based technique. However, thin-layer chromatography
      is compromised by large intra-assay and interlaboratory coefficients of
      variation. Therefore in this study we have used a reference method that is based
      on fluorescence depolarization, the TDx FLM II assay, to verify the sensitivity
      and precision of infrared spectroscopy for assessment of fetal lung maturity
      status. STUDY DESIGN: Samples of amniotic fluid were obtained by amniocentesis
      from 101 patients between the 24th and 40th weeks of pregnancy. Small volumes (35
      microL) of amniotic fluid specimens were dried, and the infrared spectra were
      measured with a commercial infrared spectrometer. The fetal lung
      surfactant/albumin ratio was determined separately for each specimen with the TDx
      FLM II assay. The proposed infrared method was then calibrated and tested with a
      partial least-squares regression analysis to quantitatively correlate the
      infrared spectra with the surfactant/albumin ratios provided by the TDx FLM II
      assays. RESULTS: A total of 144 training spectra were used to build the partial
      least-squares calibration model. The correlation coefficient for the training set
      was excellent (r = 0.92), with an SE between infrared-predicted and reference
      surfactant/albumin ratios of 17 mg/g. The model was then validated on a set of 69
      test spectra and yielded an SE of 14 mg/g (r = 0.86). The final partial least
      squares model included the 900- to 1500-cm(-1) and 2800- to 3200-cm(-1) spectral
      ranges and 6 partial least-squares factors. CONCLUSION: Because the infrared
      based fetal lung maturity measurements correlated well with assays from both of
      the current standard clinical techniques (thin-layer chromatography and
      fluorescence depolarization) and the procedure is less labor and training
      intensive, we concluded that infrared spectroscopy has the potential to emerge as
      the method of choice for prediction of fetal lung maturity from amniotic fluid
      analysis.

PMID- 10920329
TI  - Fetal erythropoietin levels in pregnancies complicated by meconium passage: does
      meconium suggest fetal hypoxia?
AB  - OBJECTIVE: We sought to determine whether umbilical cord plasma erythropoietin
      levels were different in deliveries complicated by meconium passage and to
      determine whether this response is influenced by gestational age. STUDY DESIGN:
      Fetal erythropoietin levels were measured in 203 appropriately grown neonates at
      37 to 43 weeks of gestation; among those, 70 had passed meconium. RESULTS:
      Meconium passage in the entire population was associated with elevated fetal
      erythropoietin levels (68 vs 31 mIU/mL; P <.001). Cord blood gases, pH, base
      deficit, and PO (2), as well as the 1- and 5-minute Apgar scores, were not
      different between the meconium and no-meconium groups. Gestational age and birth
      weights were significantly higher in the meconium group. Stepwise multiple
      regression analysis with meconium and gestational age used as the independent
      variables showed both meconium and gestational age to be independently associated
      with fetal erythropoietin levels (r = 0.356, F = 14.5; meconium, P <.001;
      gestational age, P <.01). CONCLUSIONS: These results suggest that meconium
      passage can be associated with chronic fetal hypoxia as demonstrated by elevated
      fetal erythropoietin levels, independent of gestational age.

PMID- 10920330
TI  - Physiologic role of nitric oxide in the maintenance of uterine quiescence in
      nonpregnant and pregnant sheep.
AB  - OBJECTIVE: This study evaluated the role of nitric oxide in the maintenance of
      uterine quiescence in nonpregnant and pregnant ewes. STUDY DESIGN: Sixteen
      ovariectomized nonpregnant and 10 pregnant (115 days' gestation) chronically
      instrumented ewes were studied. Uterine contractility was assessed by
      electromyography and intrauterine pressure recordings. Nitric oxide synthase
      inhibition was induced with nitro-L -arginine methyl ester or aminoguanidine (4.
      5 mg/kg per hour) given during estrogen replacement with 17beta-estradiol (100
      microg/d) or in late gestation. In the pregnant group we evaluated the ability of
      nitric oxide synthase inhibition to alter the responsiveness to oxytocin-induced
      uterine contractility. Blood pressure and common internal iliac artery blood flow
      were assessed to confirm nitric oxide synthase inhibition. In addition, the
      effects of the nitric oxide donor nitroglycerin and the cyclooxygenase inhibitor
      indomethacin were studied in nonpregnant sheep. The effect of nitric oxide in
      vitro on myometrial spontaneous and induced contractions was also studied.
      RESULTS: In nonpregnant estrogen-replaced sheep, nitric oxide synthase inhibition
      and nitroglycerin administration did not alter uterine contractility, despite
      significant changes in blood pressure. In contrast, indomethacin decreased
      electromyographic results to 70% of baseline after 1 hour and 47% after 2 hours.
      In pregnant ewes nitric oxide synthase inhibition failed to alter uterine
      contractility in response to oxytocin. These findings are in contrast to results
      of the in vitro study in which nitric oxide was shown to relax sheep myometrium.
      CONCLUSION: The absence of significant effects of nitric oxide synthase
      inhibition and nitric oxide donors on uterine contractility in vivo suggests that
      nitric oxide does not play a physiologic role in the regulation of uterine
      contractility in nonpregnant or pregnant ewes.

PMID- 10920331
TI  - Differential localization of placental extracellular superoxide dismutase as
      pregnancy progresses.
AB  - OBJECTIVE: The aim of this study was to determine placental localization and
      activity of extracellular superoxide dismutase, a nitric oxide modulator, during
      early gestation and to correlate these characteristics with fetal vascular
      development. STUDY DESIGN: First-trimester (n = 10) and second-trimester (n = 10)
      villi were obtained at elective pregnancy termination. Extracellular superoxide
      dismutase was localized by means of an immunoperoxidase method. Activity was
      measured by determining the inhibition of cytochrome c reduction at pH 10 and
      messenger ribonucleic acid expression by in situ hybridization. RESULTS:
      Extracellular superoxide dismutase was intracellular within villous trophoblasts
      until 17 weeks' gestation, when it relocated to the villous extracellular matrix.
      Activities were similar between first- and second-trimester villi. In situ
      hybridization confirmed extracellular superoxide dismutase messenger ribonucleic
      acid within trophoblasts throughout gestation. CONCLUSION: Extracellular
      superoxide dismutase is produced by trophoblasts early in pregnancy, but it
      remains intracellular until 17 weeks' gestation, which may be related to fetal
      vascular development.

PMID- 10920332
TI  - The effects of placental extracts from normotensive and preeclamptic women on
      vasoconstriction and oxidative metabolism.
AB  - OBJECTIVE: A circulating factor derived from the placenta has been implicated in
      the pathogenesis of preeclampsia. The aim of this study was to determine whether
      placental extracts from normotensive women and women with preeclampsia increase
      oxidative metabolism and histamine-induced vasoconstriction in porcine carotid
      artery. STUDY DESIGN: Placental extracts from normotensive women and women with
      preeclampsia were applied to porcine carotid artery, and oxidative metabolism was
      measured. Histamine-induced isometric force responses were also determined in the
      absence and presence of placental extracts. RESULTS: Application of placental
      extracts to porcine carotid artery caused a fall in oxygen tension, which
      reflects increased consumption. Extracts from placentas taken from women with
      preeclampsia caused a greater fall than those from normotensive women (0.117 +/-
      0.026 vs 0.018 +/- 0.0024 micromol oxygen per milligram; P < or =.01). Histamine
      induced contractions were potentiated by extracts from preeclampsia but not from
      those of women without hypertension. The maximal steady-state force values were
      13,137 +/- 3647, 12,921 +/- 3684, and 21,673 +/- 7189 N/m(-2) for control,
      normotensive, and preeclamptic samples at 10-micromol/L histamine (P < or =.05,
      compared with control placental extracts). CONCLUSIONS: Placental extracts from
      women with preeclampsia cause a greater stimulation of porcine artery oxygen
      consumption and exacerbation of histamine-induced vasoconstriction than extracts
      from normotensive women.

PMID- 10920333
TI  - Long-term outcome in twin-twin transfusion syndrome treated with serial
      aggressive amnioreduction.
AB  - OBJECTIVE: The purpose of this study was to determine long-term outcomes among
      pregnancies complicated by twin-twin transfusion syndrome and treated in a
      tertiary center with serial aggressive amnioreduction. STUDY DESIGN: Thirty-three
      pregnancies with a diagnosis of twin-twin transfusion syndrome were treated with
      > or =1 amnioreduction. The perinatal outcome was assessed according to 15
      parameters, whereas the main outcome at age > or =2 years was the absence of
      cerebral palsy. RESULTS: Gestational age at diagnosis ranged from 14.5 to 33
      weeks' gestation (median, 20.6 weeks' gestation), whereas gestational age at
      delivery was between 18.5 and 37 weeks' gestation (median, 30.5 weeks'
      gestation). The number of amnioreductions per pregnancy ranged from 1 to 15
      (median, 2). At initial examination hydrops of the recipient and absence of the
      end-diastolic velocity of the umbilical artery in one of the twins were
      associated with poor prognosis. Fifty-one (77%) twins were born alive. At 24
      months after birth both infants from 57% of the pregnancies (19/33) were alive,
      whereas at least one infant from 70% of the pregnancies (23/33) was alive. Thirty
      three infants (78% of the survivors) were older than 36 months at last follow-up.
      Cerebral palsy was diagnosed in 2 of 42 infants (4.7%). One of the affected
      infants was born after the fetal death of the cotwin; the other infant was born
      with congenital cardiac malformations. CONCLUSIONS: In the group of fetuses in
      which both twins were delivered alive after 27 weeks' gestation without
      congenital malformations and survived the neonatal period, no major neurologic
      handicaps developed in any of the infants. At initial examination both hydrops of
      the recipient and absence of end-diastolic flow velocity waveforms of the
      umbilical artery in one of the twins were poor prognostic signs.

PMID- 10920334
TI  - Umbilical cord blood collection before placental delivery during cesarean
      delivery increases cord blood volume and nucleated cell number available for
      transplantation.
AB  - OBJECTIVE: We sought to determine whether umbilical cord blood collection during
      cesarean delivery can be improved by collecting cord blood before delivery of the
      placenta. STUDY DESIGN: Patients undergoing cesarean delivery were randomly
      assigned to cord blood collection before or after placental delivery. Closed
      sterile collection systems were used for blood sampling. Cord blood
      characteristics and maternal outcome parameters were compared between the 2
      groups. RESULTS: A total number of 40 patients were available for analysis. No
      differences in maternal and neonatal characteristics were found. A larger amount
      of cord blood volume (mean +/- SEM, 93 +/- 7.5 vs 66 +/- 6.6 mL; P =.013) and
      total nucleated cell number (11.1 +/- 1.2 vs 7.4 +/- 0.8 x 10(8) cells; P =.026)
      was obtained in the samples collected before compared with those collected after
      placental delivery. Similarly, there was a trend toward higher total CD34(+) cell
      number in samples collected in situ (30.0 +/- 6.0 vs 17.4 +/- 2.4 x 10(5) cells;
      P =.076). Estimated intraoperative blood loss, difference between prepartum and
      postpartum hemoglobin values, operating time, and puerperal infection rates were
      similar in both groups. CONCLUSION: If a cesarean delivery is performed, cord
      blood sampling is more efficacious if performed before delivery of the placenta.
      This collection method seems beneficial and safe and might therefore be
      preferably used for related, as well as unrelated, cord blood stem cell banking
      and transplantation.

PMID- 10920335
TI  - Detection of fetal trisomy 18 by short-term culture of maternal peripheral blood.
AB  - OBJECTIVE: We report the prenatal detection by fluorescence in situ hybridization
      analysis of a male fetus with trisomy 18. STUDY DESIGN: Total nucleated cells
      recovered from 7 mL of maternal peripheral blood by means of double-density
      gradient centrifugation were cultured for 3 days in a devised medium. RESULTS:
      Fetal cells with X- and Y-specific signals were detected in all the established
      cultures, but the yield and purity were higher in the culture from the 1077
      Ficoll layer. Cumulatively, 84 fetal cells were recorded by analysis of 5640
      cells. The hematopoietic lineages involved in the production of the fetal cells
      in culture were not assessed. For the cultures established with the 1119 Ficoll
      layer, the involvement of progenitors or precursors of the erythroid lineage was
      assumed because postculture sorting was directed toward cells expressing the
      erythropoietin receptor. CONCLUSION: We conclude that culturing total nucleated
      cells from maternal blood is a new procedure that could prove valuable in the
      detection of the main fetal aneuploidies affecting pregnant populations.

PMID- 10920336
TI  - Acute maternal rehydration increases the urine production rate in the near-term
      human fetus.
AB  - OBJECTIVE: We sought to investigate the effect of a decrease of maternal plasma
      osmolality produced by hypotonic rehydration on the fetal urine production rate
      in normal near-term human fetuses. STUDY DESIGN: Twenty-one healthy pregnant
      women attending the clinic for antenatal care were studied between 37 and 40
      weeks' gestation. The fetal urine production rate was assessed by serial
      measurements of 3 diameters of the fetal bladder. The hourly fetal urine
      production rate was determined by linear regression analysis of the calculated
      bladder volumes versus time and was initially determined after a period of 4
      hours of fluid deprivation. Thereafter, the women were asked to drink 1 L of
      water, and the hourly fetal urine production rate was assessed again. The hourly
      fetal urine production rate was only studied during behavioral state 1F because
      it is dependent on the behavioral state. The fetal behavioral state was
      determined by assessment of fetal heart rate, fetal eye movements, and fetal body
      movements. RESULTS: Successful recordings were obtained in 10 of the 21 women.
      The hourly fetal urine production rate increased significantly after hypotonic
      rehydration (P <.02). Compared with the initial hourly fetal urine production
      rate after 4 hours of fluid deprivation, the hourly fetal urine production rate
      showed an increase of 63.2% after hypotonic rehydration, from 38.2 +/- 16.3 mL/h
      to 62.4 +/- 34.6 mL/h (mean +/- SD). After rehydration, the baseline fetal heart
      rate fell significantly, from 141 +/- 6 to 132 +/- 8 beats/min (mean +/- SD; P
      =.005). CONCLUSION: The fetal urine production rate is augmented after acute
      maternal oral hypotonic rehydration after 4 hours of fluid deprivation. The
      current findings demonstrate that the near-term human fetus can handle such acute
      changes in fluid osmolality by increasing the urine production rate to maintain
      its fluid homeostasis. This mechanism implies that changes in maternal plasma
      osmolality and volume probably play an important role in determining amniotic
      fluid volume. Therefore the application of maternal hydration for the treatment
      of oligohydramnios should be further investigated.

PMID- 10920337
TI  - Ultrasonographic ear length measurement in normal second- and third-trimester
      fetuses.
AB  - OBJECTIVE: We sought to develop a nomogram for fetal ear length measurements from
      a large population of healthy second- and third-trimester fetuses and to
      investigate the correlation of fetal ear length with other standard fetal
      biometry measurements, as follows: biparietal diameter, head circumference,
      abdominal circumference, femur length, and humerus length. STUDY DESIGN: Ear
      length measurement was obtained prospectively in 4240 singleton fetuses between
      15 and 40 weeks' gestational age. Either complete data for normal karyotype on
      amniocentesis or normal infant examination at birth or both were available in
      2583 cases. These constituted the final study population. RESULTS: A nomogram was
      developed by linearly regressing ear length on gestational age (Ear length [in
      millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high
      correlation between ear length and gestational age (r = 0.96; P =.0001).
      CONCLUSION: The results of this study provide normative data on growth of fetal
      ear length from 15 to 40 weeks' gestation. Good correlation was also observed
      between ear length and other fetal biometric measurements (biparietal diameter,
      head circumference, abdominal circumference, femur length, and humerus length).

PMID- 10920338
TI  - The association between meconium and the production and reabsorption of lung
      liquid and lactate loss by in vitro lungs from fetal guinea pigs.
AB  - OBJECTIVE: We sought to use an in vitro approach to determine relationships
      between meconium and fetal lung liquid production and to relate meconium to
      possible problems in lung liquid removal at birth. STUDY DESIGN: Near-term fetal
      guinea pigs were divided according to the level of spontaneously occurring
      meconium (no meconium, light meconium, or heavy meconium). Their lungs were
      maintained in vitro in Krebs-Henseleit saline solution for 3 hours. Lung liquid
      production or reabsorption was measured by a dye-dilution method, and loss of
      lactate to the lung liquid and outer Krebs-Henseleit solution was monitored.
      Reabsorptions were investigated by activating powerful responses with
      dinitrophenol during the middle hour. RESULTS: During the first hour, lungs from
      meconium-free fetuses produced liquid at 1.25 +/- 0.12 mL/kg(-1) body weight. h(
      1); rates from light or heavy meconium groups were not significantly different (n
      = 18). Similarly, total lactate loss was not significantly different between the
      meconium-free and light-meconium groups but was twice as high in heavy-meconium
      preparations (73.68 +/- 10.60 micromol/L. g(-1) dry lung tissue. h(-1); P <.025,
      analysis of variance). The meconium-free and heavy-meconium groups continued to
      produce fluid, with no significant change throughout the 3 hours of incubation;
      lactate losses fell slightly. Therefore there were no problems with fluid
      production with meconium present, but the high-lactate losses with heavy meconium
      suggested long-term intrauterine hypoxia. Dinitrophenol produced powerful
      reabsorptions in lungs from meconium-free fetuses (-0.85 +/- 0.35 mL. kg(-1) body
      weight. h(-1); P <.005, analysis of variance; P <.0005, regression analysis) but
      failed to do so in heavy-meconium fetuses (n = 36). Lactate losses rose 2-fold in
      both groups (P <.005 to P < 0.0005, analysis of variance and regression
      analysis), despite already elevated losses with heavy meconium (n = 12).
      Therefore, in heavy-meconium fetuses, dinitrophenol affected metabolic pathways
      but did not activate fluid reabsorption, suggesting damage to reabsorptive
      mechanisms. CONCLUSION: Unless major airways are blocked, meconium is not
      associated with reduced fetal lung liquid production, which can cause poor lung
      development, but there may well be poor fluid removal after birth because of
      compromised reabsorptive mechanisms, which are unlikely to be helped by possible
      hormonal intervention.

PMID- 10920339
TI  - Consented testing of newborns and childbearing women for human immunodeficiency
      virus through a newborn metabolic screening program.
AB  - OBJECTIVE: In this program a postpartum woman could consent to receive her
      newborn's human immunodeficiency virus test result from the New York State
      Newborn Screening Program. STUDY DESIGN: By state regulation each postpartum
      woman was counseled and offered her newborn's human immunodeficiency virus test
      result. With the mother's consent, newborn human immunodeficiency virus antibody
      test results from the Newborn Screening Program were sent to the baby's
      pediatrician; otherwise, test results were blinded. Data were analyzed for births
      from August 1, 1996, to January 31, 1997. RESULTS: Overall, 92.5% of women
      offered newborn human immunodeficiency virus testing consented to receive the
      result. Among 444 human immunodeficiency virus-positive women offered newborn
      testing, consented testing resulted in a 21.4% increase in knowledge of human
      immunodeficiency virus status from 72.3% (n = 321) at delivery to 93.7% (n = 416)
      after newborn testing; 6.3% (n = 28) of human immunodeficiency virus-positive
      women delivered of infants who did not consent apparently remained unaware of
      their human immunodeficiency virus status. CONCLUSION: Combined prenatal and
      consented newborn testing identified 94% of human immunodeficiency virus-positive
      mothers and exposed newborns, allowing early entry into care. Such testing may
      provide an opportunity for women not previously tested for the human
      immunodeficiency virus to learn their status but is not a substitute for
      universal prenatal human immunodeficiency virus counseling and consented human
      immunodeficiency virus testing.

PMID- 10920340
TI  - Individual immunity and susceptibility to female genital tract infection.
AB  - The responses to genital tract infection vary among different women to a far
      greater extent than has previously been appreciated. All women are not
      genetically identical and have not been exposed to identical environments;
      therefore it is naive to expect that a particular microorganism will elicit the
      identical response and have the identical sequelae for each infected individual.
      The genes inherited from one's parents, which contain specific polymorphisms in
      immune response genes, greatly influence the direction and magnitude of the
      immune response to microorganisms. Similarly, extrinsic variables, such as the
      type or quantity of a specific infection, whether there is a coinfection with
      another microorganism, such as an intracellular parasite, and whether an
      immediate hypersensitivity response is concurrently induced also determine the
      nature of the host response and thus the consequences of microbial exposure.
      Finally, factors such as the frequency of sexual intercourse and previous immune
      sensitization to spermatozoa or other components of a particular ejaculate also
      influence the outcome. An increased awareness of the uniqueness of each host will
      lead to the development of more precise individualized treatments and
      improvements in combating infectious diseases of the female genital tract.

PMID- 10920341
TI  - Choriocarcinoma after hydatidiform mole.

PMID- 10920342
TI  - Questionable statistics in meta-analysis.

PMID- 10920344
TI  - Epidural anesthesia in severe preeclampsia.

PMID- 10920346
TI  - Report of the National High Blood Pressure Education Program Working Group on
      High Blood Pressure in Pregnancy.
AB  - This report updates the 1990 "National High Blood Pressure Education Program
      Working Group Report on High Blood Pressure in Pregnancy" and focuses on
      classification, pathophysiologic features, and management of the hypertensive
      disorders of pregnancy. Through a combination of evidence-based medicine and
      consensus this report updates contemporary approaches to hypertension control
      during pregnancy by expanding on recommendations made in "The Sixth Report of the
      Joint National Committee on Prevention, Detection, Evaluation, and Treatment of
      High Blood Pressure." The recommendations to use Korotkoff phase V for
      determination of diastolic pressure and to eliminate edema as a criterion for
      diagnosing preeclampsia are discussed. In addition, the use as a diagnostic
      criterion of blood pressure increases of 30 mm Hg systolic or 15 mm Hg diastolic
      with blood pressure <140/90 mm Hg has not been recommended, because available
      evidence shows that women with blood pressures fitting this description are not
      more likely to have adverse outcomes. Management distinctions are made between
      chronic hypertension that is present before pregnancy and hypertension that
      occurs as part of the pregnancy-specific condition of preeclampsia, as well as
      management considerations for women with comorbid conditions. A discussion of the
      pharmacologic treatment of hypertension during pregnancy includes recommendations
      for specific agents. The use of low-dose aspirin, calcium, or other dietary
      supplements in the prevention of preeclampsia is described, and expanded sections
      on counseling women for future pregnancies and recommendations for future
      research are included.

PMID- 10920347
TI  - SIMSUG 2000: stable isotope mass spectrometry users group meeting

PMID- 10920348
TI  - Isotopic composition of inorganic carbon as an indicator of benzoate degradation
      by pseudomonas putida: temperature, growth rate and pH effects.
AB  - Degradation experiments of benzoate by Pseudomonas putida resulted in enzymatic
      carbon isotope fractionations. However, isotopic temperature effects between
      experiments at 20 and 30 degrees C were minor. Averages of the last three values
      of the CO(2) isotopic composition (delta(13)C(CO2(g))) were more negative than
      the initial benzoate delta(13)C value (-26.2 per thousand Vienna Pee Dee Belenite
      (VPDB)) by 3.8, 3.4 and 3.2 per thousand at 20, 25 and 30 degrees C,
      respectively. Although the maximum isotopic temperature difference found was only
      0.6 per thousand, more extreme temperature variations may cause larger isotope
      effects. In order to understand the isotope effects on the total inorganic carbon
      (TIC), a better measure is to calculate the proportions of the inorganic carbon
      species (CO(2)(g), CO(2)(aq) and HCO(3)(-)) and to determine their cumulative
      delta(13)C(TIC). In all three experiments delta(13)C(TIC) was more positive than
      the initial isotopic composition of the benzoate at a pH of 7. This suggests an
      uptake of (12)C in the biomass in order to match the carbon balance of these
      closed system experiments.

PMID- 10920349
TI  - (13)C natural abundance in the British diet: implications for (13)C breath tests.
AB  - Surprisingly little information is available on the natural abundance of the
      minor isotope of carbon, (13)C, in common foodstuffs in the British diet. This
      study therefore aimed to examine the (13)C natural abundance of foodstuffs from a
      small cross-section of the British diet. The isotopic abundance, delta per mil,
      was calculated by measurement of the isotope ratio (13)C:(12)C by isotope ratio
      mass spectrometry. Results from this study were also compared with results from a
      North American study to highlight the difference in isotopic abundance between
      Northern European foodstuffs and North American foodstuffs. Such data should
      prove useful to those planning tracer studies using the stable isotope (13)C
      where enrichment is measured against a large and variable natural abundance in
      the body. Minimisation of this basal variation, for example in breath CO(2), can
      be achieved by controlling dietary intake of foods naturally abundant in (13)C.

PMID- 10920350
TI  - Identifying migratory Salmo trutta using carbon and nitrogen stable isotope
      ratios.
AB  - Many Salmo trutta populations consist of non-anadromous (freshwater-resident)
      brown trout and anadromous (sea-run migratory) sea trout. Although adult brown
      trout and sea trout can usually be identified using differences in size and body
      colouration, it is not possible to easily identify eggs/alevins as the progeny of
      brown trout or sea trout. In this study we show that delta(13)C and delta(15)N,
      measured using a continuous flow isotope ratio mass spectrometer (CF-IRMS), can
      accurately identify fish eggs as the progeny of freshwater-resident
      (delta(13)C(egg) = -25.7 +/- 1.9 per thousand,delta(15)N(egg) = 9.2 +/- 1.8 per
      thousand) or migratory (delta(13)C(egg) = -19.9 +/- 1.1 per thousand,
      delta(15)N(egg) = 14. 3 +/- 1.5 per thousand) adult female Salmo trutta. Case
      studies show that stable isotope analysis is a more reliable technique for
      distinguishing anadromous adult fish than differentiation using morphological
      characteristics. For example, stable isotope analysis of brown trout from Loch
      Eck, Scotland, revealed that some individuals possessed delta(13)C and delta(15)N
      signatures indicative of marine feeding despite visual identification as
      freshwater-resident fish. It is most likely that these fish are misidentified sea
      trout although it possible that these fish may be brown trout that have adopted
      an estuarine feeding strategy to avoid interspecific competition for food within
      Loch Eck with salmon, powan and Arctic charr. Most stable isotope studies of fish
      ecology use terminal tissue sampling to provide sufficient biological material
      for isotopic analysis; however, our study suggests that adipose fin tissue could
      provide a comparable measure of delta(13)C and delta(15)N. Such a strategy would
      be invaluable when studying the trophic ecology or migration patterns of fish of
      high conservation value.

PMID- 10920351
TI  - (18)O/(16)O and (13)C/(12)C in an ahermatypic deep-water coral Lophelia pertusa
      from the North Atlantic: a case of disequilibrium isotope fractionation.
AB  - The numerous stable isotope studies of scleractinian photosynthetic reef-building
      corals in tropical seas have demonstrated the complexity of the biological and
      environmental factors that give rise to their isotopic composition. Scleractinian
      non-photosynthetic corals of the deep cold water environment might be expected to
      reflect the more stable physical environment in the deep sea. However, in
      comparison, little is known about their isotope systematics. The present study
      concentrates on specimens of Lophelia pertusa from the north-eastern Atlantic,
      the Norwegian Shelf and Fjord. Aliquots taken from the theca represent time
      series and show variations in delta(13)C and delta(18)O of up to 4.7 and 2.4 per
      thousand, respectively. The variations seem to be related to morphological
      features of branching. The tendency of higher values near the tip of the polyps
      reported previously was detected only in some samples. The delta(18)O of the
      corals are in all cases more negative than the equilibrium values. There is a
      strong correlation between delta(13)C and delta(18)O forming linear arrays. The
      difference between these arrays is more pronounced in delta(13)C. The covariation
      of delta(13)C and delta(18)O indicates an overruling 'kinetic isotope effect'.
      This is in line with the behaviour of some trace elements. This isotope effect
      should be regarded as one manifestation of variations in partition coefficients
      dictated by a biological control on mineralisation (such as food or reproduction)
      rather than changes in the relative contribution of metabolic carbon affecting
      delta(13)C, and changes in temperature affecting delta(18)O.

PMID- 10920352
TI  - Compound-specific isotope analysis. Application to archaeology, biomedical
      sciences, biosynthesis, environment, extraterrestrial chemistry, food science,
      forensic science, humic substances, microbiology, organic geochemistry, soil
      science and sport.
AB  - The isotopic composition, for example, (14)C/(12)C, (13)C/(12)C, (2)H/(1)H,
      (15)N/(14)N and (18)O/(16)O, of the elements of matter is heterogeneous. It is
      ruled by physical, chemical and biological mechanisms. Isotopes can be employed
      to follow the fate of mineral and organic compounds during biogeochemical
      transformations. The determination of the isotopic composition of organic
      substances occurring at trace level in very complex mixtures such as sediments,
      soils and blood, has been made possible during the last 20 years due to the rapid
      development of molecular level isotopic techniques. After a brief glance at
      pioneering studies revealing isotopic breakthroughs at the molecular and
      intramolecular levels, this paper reviews selected applications of compound
      specific isotope analysis in various scientific fields.

PMID- 10920353
TI  - Carbon assimilation and turnover in grassland vegetation using an in situ
      (13)CO(2) pulse labelling system.
AB  - A mobile laboratory was developed to administer a controlled flow of (13)C
      labelled CO(2) at ambient concentrations ( approximately 350 ppm) in the field.
      The stable isotope delivery (SID) system consists of an isotope-mixing unit with
      flow control to a series of 12 independent labelling chambers. In-line CPU
      controlled infrared gas analysers allow automated measurement of chamber CO(2)
      concentrations and gas flow management. A preliminary experiment was established
      on an upland pasture located at the NERC Soil Biodiversity experimental site,
      Sourhope, UK, in August 1999. The objective of this investigation was to
      determine the magnitude of pulse-derived C incorporation into a typical upland
      plant community. To achieve this, the SID system was deployed to pulse-label
      vegetation with CO(2) enriched with (13)C (50 atom %) at ambient concentrations (
      approximately 350 ppm) on two consecutive days in August 1999. Samples of
      headspace CO(2), shoot and root were taken on four occasions over a period of 28
      days after (13)C labelling. These materials were then prepared for (13)C/(12)C
      ratio determination by continuous-flow/combustion/isotope ratio mass spectrometry
      (CF-C-IRMS). Results showed that pulse derived CO(2)-C was assimilated at a rate
      of 128 +/- 32 microg g shoot-C hour(-1). Dynamic samplings showed that pulse
      derived (13)C concentrations in the labelled plant tissues declined by 77.4 +/-
      6% after 48 hours. The rapid decline in (13)C concentrations in plant matter was
      the result of C loss from the plant in the form of respired CO(2) and root
      exudates, and dilution by subsequent unlabelled C assimilates. This novel system
      offers considerable potential for in situ tracer investigations.

PMID- 10920354
TI  - Amino acids as a nitrogen source in temperate upland grasslands: the use of dual
      labelled ((13)C, (15)N) glycine to test for direct uptake by dominant grasses.
AB  - It is becoming increasingly apparent that soil amino acids are a principal source
      of nitrogen (N) for certain plants, and especially those of N-limited
      environments. This study of temperate upland grasslands used glycine-2-(13)C
      (15)N and ((15)NH4)(2)SO(4) labelling techniques to test the hypothesis that
      plant species which dominate 'unimproved' semi-natural grasslands (Festuca
      Agrostis-Galium) are able to utilise amino acid N for growth, whereas those
      plants which dominate 'improved' grasslands (Lolium-Cynosurus), that receive
      regular applications of inorganic fertiliser, use inorganic N forms as their main
      N source. Data from field experiments confirmed that 'free' amino acids were more
      abundant in 'unimproved' than 'improved' grassland and that glycine was the
      dominant amino acid type (up to 42% of total). Secondly, the injection of
      representative amounts of glycine-2-(13)C-(15)N (4.76 and 42.86 mM) into intact
      soil cores from the two grassland types provided evidence of direct uptake of
      glycine by plants, with both (15)N and (13)C being detected in plant material of
      both grasslands. Finally, a microcosm experiment demonstrated no preferential
      uptake of amino acid N by the grasses which dominate the grassland types, namely
      Holcus lanatus, Festuca rubra, Agrostis capillaris from the 'unimproved'
      grassland, and Lolium perenne from the 'improved' grassland. Again, both (13)C
      and (15)N were detected in all grass species suggesting uptake of intact glycine
      by these plants.

PMID- 10920355
TI  - Effects of dung and urine amendments on the isotopic content of N(2)O released
      from grasslands.
AB  - The temporal and diurnal changes in nitrous oxide (N(2)O) fluxes were measured
      between 29(th) September and 2(nd) November 1999 from urine and dung patches from
      cattle deposited on grazed grassland. The delta(15)N and delta(18)O values of the
      N(2)O emitted from soil from both treatments were examined on four occasions
      during this period. The diurnal fluxes of N(2)O were measured by a chamber
      technique that provides hourly measurement of N(2)O fluxes. The (15)N and (18)O
      analysis of N(2)O were determined by isotope ratio mass spectrometry. N(2)O
      fluxes from the excreta patches were large, with peak emissions up to 1893 ng N
      m(-2) s(-1) occurring after heavy precipitation, measured one month after the
      treatment applications. Emissions from the urine patches were significantly
      greater than from the dung. The results showed that excretal patches are an
      important source of atmospheric N(2)O. The flux pattern showed a strong diurnal
      variation with maximum fluxes generally occurring in late afternoon or early
      morning, and generally not in phase with the soil temperature changes. The
      isotopic content of (15)N and (18)O in the N(2)O showed a similar trend to that
      of the N(2)O flux. The (15)N and (18)O values of the N(2)O emitted from the soil
      indicated that denitrification was the major process involved. After heavy
      precipitation on the 6(th) October, the larger delta(15)N and delta(18)O values
      suggested a consumption of the N(2)O by total denitrification.

PMID- 10920356
TI  - Incorporation of (15)N from spiked cattle dung pats into soil under two moorland
      plant communities.
AB  - The rate and depth of cattle dung incorporation into moorland soil may be an
      important factor influencing plant community dynamics through its effects on soil
      nutrient availability. This study traces the incorporation of (15)N-labelled dung
      into a moorland soil under two vegetation types in Dartmoor National Park, UK.
      Cores of treated and control soil 10 cm deep were collected at 2, 4, 8 and 16
      week intervals and divided into 2 cm depth increments. Soil samples were freeze
      dried, ground and analysed for atom% (15)N and %N content using continuous-flow
      isotope-ratio mass spectrometry. The contribution of dung N to the soil N pool
      was estimated by changes in atom% (15)N of the soil. The incorporation of dung
      dry matter into the soil was also calculated. The labile component of the dung N
      was incorporated deeper and more rapidly into soil under grass than under heather
      vegetation. The implications of these processes for the dynamics of upland plant
      communities are considered in relation to the ability of plants to compete for
      nutrients.

PMID- 10920357
TI  - The significance of monoisotopic and carbon-13 isobars for the identification of
      a 19-component dodecapeptide library by positive ion electrospray Fourier
      transform ion cyclotron resonance mass spectrometry.
AB  - Harnessing the ultra high resolution capabilities of Fourier transform ion
      cyclotron resonance mass spectrometry (FTICR-MS) and positive ion electrospray,
      we have demonstrated the significance and utility of cumulative mass defect high
      resolution mass separation stable isotope distribution, exact mass measurement
      and elemental formula as a means of simultaneously identifying 19 components of
      the dodecapeptide library Ac-ANKISYQS[X]STE-NH(2). With an instrument resolution
      of 275 000 (average), isobaric multiplets attributed to monoisotopic and carbon
      13 components of peptides: Ac approximately SLS approximately NH(2); Ac
      approximately SNS approximately NH(2); Ac approximately SOS approximately NH(2);
      Ac approximately SDS approximately NH(2); within the mass window of 1380-1385 Da,
      and Ac approximately SQS approximately NH(2); Ac approximately SKS approximately
      NH(2); Ac approximately SES approximately NH(2); Ac approximately SMS
      approximately NH(2), within the mass window 1395-1400 Da, were mass resolved,
      accurately mass measured and identified from the computed molecular formulas.
      This experimental procedure enabled the separation of monoisotopic and carbon-13
      isobars yielding enhanced selectivity and specificity and serves to illustrate
      the significance of monoisotopic and carbon-13 isobars in final product analysis.
      Chromatographic separation (HPLC) was of limited utility except for monitoring
      the overall extent of reaction and apparent product distribution. Positive ion
      electrospray-FTICR-MS and fast atom bombardment (FAB) MS were used to assess
      final product quality and apparent component distribution.

PMID- 10920358
TI  - Integration of immobilized trypsin bead beds for protein digestion within a
      microfluidic chip incorporating capillary electrophoresis separations and an
      electrospray mass spectrometry interface.
AB  - A microfluidic device is described in which an electrospray interface to a mass
      spectrometer is integrated with a capillary electrophoresis channel, an injector
      and a protein digestion bed on a monolithic substrate. A large channel, 800
      microm wide, 150 microm deep and 15 mm long, was created to act as a reactor bed
      for trypsin immobilized on 40-60 microm diameter beads. Separation was performed
      in channels etched 10 microm deep, 30 microm wide and about 45 mm long, feeding
      into a capillary, attached to the chip with a low dead volume coupling, that was
      30 mm in length, with a 50 microm i.d. and 180 microm o.d. Sample was pumped
      through the reactor bed at flow rates between 0.5 and 60 microL/min. The
      application of this device for rapid digestion, separation and identification of
      proteins is demonstrated for melittin, cytochrome c and bovine serum albumin
      (BSA). The rate and efficiency of digestion was related to the flow rate of the
      substrate solution through the reactor bed. A flow rate of 1 or 0.5 microL/min
      was found adequate for complete consumption of cytochrome c or BSA, corresponding
      to a digestion time of 3-6 min at room temperature. Coverage of the amino acid
      sequence ranged from 92% for cytochrome c to 71% for BSA, with some missed
      cleavages observed. Melittin was consumed within 5 s. In contrast, a similar
      extent of digestion of melittin in a cuvet took 10-15 min. The kinetic
      limitations associated with the rapid digestion of low picomole levels of
      substrate were minimized using an integrated digestion bed with hydrodynamic flow
      to provide an increased ratio of trypsin to sample. This chip design thus
      provides a convenient platform for automated sample processing in proteomics
      applications.

PMID- 10920359
TI  - Direct analysis of plasma samples for drug discovery compounds using mixed
      function column liquid chromatography tandem mass spectrometry.
AB  - A sensitive, efficient, high throughput, direct injection bioanalytical method
      based on a single column and high-performance liquid chromatography (HPLC) with
      tandem mass spectrometry (MS/MS) was developed for pharmacokinetic analysis of
      early drug discovery compounds in plasma samples. After mixing with a working
      solution containing an internal standard each plasma sample was directly injected
      into a polymer-coated mixed-function column for sample cleanup, enrichment and
      chromatographic separation. The stationary phase incorporates hydrophilic
      polyoxyethylene groups and hydrophobic groups to the polymer-coated silica. This
      allows proteins and macromolecules to pass through the column due to restricted
      access to the surface of the packing while retaining the drug molecules on the
      bonded hydrophobic phase. The analytes retained in the column with a largely
      aqueous liquid mobile phase were then chemically separated by switching to a
      strong organic mobile phase. The column effluent was diverted from waste to the
      mass spectrometer for analyte detection. Within 200 plasma sample injections the
      response ratio (analyte vs. internal standard, %CV = 4.6) and the retention times
      for analyte and internal standard were found consistent and no column
      deterioration was observed. The recoveries of test compound in various plasma
      samples were greater than 90%. The total analysis time was </=5 min per sample.

PMID- 10920360
TI  - Pulsed helium introduction into a quadrupole ion trap for reduced collisional
      quenching during infrared multiphoton dissociation of electrosprayed ions
AB  - Previous infrared multiphoton dissociation (IRMPD) experiments utilizing a
      quadrupole ion trap mass spectrometer yielded limited photodissociation
      efficiencies. Helium buffer gas continuously infused into the analyzer region at
      pressures of typically 1 x 10(-3) Torr to improve ion trap performance can
      collisionally quench photoexcited ions during the IRMPD process.
      Photodissociation experiments have indicated that uncorrected pressures below 2 x
      10(-5) Torr are necessary to avoid collisional deactivation of photoexcited ions.
      This paper describes IRMPD in the quadrupole ion trap at reduced pressures
      utilizing a dual-pulsed introduction of helium buffer gas incorporated into the
      ion trap scan function. The pulsed introduction of helium buffer gas before ion
      injection allows the efficient trapping of ions injected from an electrospray
      source and the removal of helium before laser irradiation. A second pulse of
      helium directly before ion detection improves the intensity of the ion signal.
      The use of this dual-pulsed inlet of helium for improved IRMPD is demonstrated
      with the carbohydrate antibiotics neomycin and erythromycin. Copyright 2000 John
      Wiley & Sons, Ltd.

PMID- 10920361
TI  - Interpretation of electrospray/ion trap mass spectra of bile acids and other
      surfactants.
AB  - Electrospray spectra of various bile acids and other surfactants were obtained
      using an ion trap instrument. Bile acids and bile acid derivatives such as 3-[(3
      cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS) self associate to
      form micelles in a stepwise process. Their spectra show a distinct pattern of
      aggregation, with ions evenly separated in the m/z space. A new parameter, n/z,
      can be used to characterize such ions, where n is the number of molecules and z
      is the charge of the aggregate. The values of z were determined using multi-stage
      mass spectrometry (MS(n)) and high resolution in the ion trap.

PMID- 10920362
TI  - Confirmatory assay for the simultaneous detection of penicillins and
      cephalosporins in milk using liquid chromatography/tandem mass spectrometry.
AB  - A high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS)
      method for the detection of residues of penicillins and cephalosporins in milk
      has been developed. After a simple extraction with acetonitrile, the extract was
      directly injected into the LC/MS/MS system on a C(18) column. A gradient
      consisting of acetonitrile and water, each containing 0.1% formic acid, was
      applied. The abundant parent ions [M + H](+) produced by positive electrospray
      ionisation were selected for fragmentation with argon. For each compound at least
      one fragment was recorded with multiple reaction monitoring. The limits of
      detection ranged from 1.5 to 25 microg/kg and the limits of quantification ranged
      from 4 to 50 microg/kg. Recoveries were examined at three levels (MRL, 0.5 x MRL,
      2 x MRL) and ranged from 57 to 88%. The coefficients of variation obtained for
      the repeatability experiments were in agreement with those specified by the
      Horwitz equation. Linearity was checked by injecting extracts of samples spiked
      with increasing amounts of the different standards ranging from 0 to 150
      microg/kg. The advantage of this method over existing methods is the very simple
      sample pre-treatment which makes the method very suitable for routine analysis.

PMID- 10920363
TI  - Electrospray and chemical ionization mass spectrometry of di-n-butyl sulfate.
      Unimolecular chemistry of its protonated form and quantification method by liquid
      chromatography/electrospray ionization tandem mass spectrometry
AB  - Di-n-butyl sulfate (DNBS) has been studied by electrospray (ESI) and chemical
      (CI) ionization mass spectrometry. The use of methanol as solvent in electrospray
      ionization allows observation of relatively abundant [DNBS + CH(3)OH + H](+) ions
      (m/z 243) which upon collision dissociate to [DNBS + H](+) ions (m/z 211). In
      both ESI and CI experiments, it is found that [DNBS + H](+) ions lead to m/z 113
      daughter ions. The composition of this m/z 113 fragment ion and its mechanism of
      formation have been established by high resolution measurements and CID-MIKE
      experiments. An 'internal substitution' reaction involving an ion-neutral
      intermediate is proposed to explain the formation of a [C(8)H(17)](+) ion (m/z
      113) by loss of a H(2)SO(4) molecule. Finally, a LC/ESI-MS/MS quantification
      method is proposed in which a detection limit of di-n-butyl sulfate in the ppm
      range is obtained. It is suggested that the quantification method might be
      extended to higher dialkyl sulfates. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10920364
TI  - Pyrolysis/gas chromatography/mass spectrometry monitoring of fungal-biotreated
      distillery wastewater using Trametes sp. I-62 (CECT 20197).
AB  - Distillery wastewaters generated by ethanol production from fermentation of sugar
      cane molasses, named vinasses, lead to important ecological impact due to their
      high content of soluble organic matter and their intense dark-brown color. Taking
      advantage of the well-known ability of white-rot fungi to degrade an extensive
      variety of organic pollutants, the capacity of Trametes sp. I-62 (CECT 20197) to
      detoxify this type of effluents was evaluated. In this work, pyrolysis/gas
      chromatography/mass spectrometry was applied to the chemical characterization of
      several fractions of Cuban distillery wastewater as well as to monitoring the
      changes which occurred after fungal treatment with this white-rot basidiomycete.
      Maximum effluent decolorization values and chemical oxygen demand reduction
      attained after seven days of fungal treatment were 73.3 and 61.7%, respectively,
      when 20% (v/v) of distillery vinasses was added to the culture medium. Under
      these conditions a 35-fold increase in laccase production by Trametes sp. I-62
      was measured, but no manganese peroxidase activity could be detected. The
      pyrolysis/gas chromatography/mass spectrometry results showed a decrease in a
      number of pyrolysis products after seven days of fungal treatment, mainly furan
      derivatives. The decrease in the relative areas of these compounds could be
      related to the vinasse color-removal associated with melanoidin degradation. All
      these results indicated the potential use ofTrametes sp. I-62 in the
      detoxification of recalcitrant distillery vinasses.

PMID- 10920365
TI  - Determination of metrifonate enantiomers in blood and brain samples using liquid
      chromatography on a chiral stationary phase coupled to tandem mass spectrometry.
AB  - A novel enantioselective assay is described for the simultaneous determination of
      the metrifonate enantiomers BAY z 7216 and BAY z 7217 in extracts of whole blood
      samples obtained from rats, mice, rabbits and Beagle dogs as well as in rat brain
      tissue using liquid chromatography tandem mass spectrometry (LC/MS/MS) with
      thermally and pneumatically assisted electrospray ionization (TurboIonSpray(R)).
      Chromatographic separation is achieved on a chiral normal phase column with a
      mobile phase containing 0.25% water only. The total run time per sample is 11.0
      min giving chromatographic base line separation of the enantiomers. Compared with
      previous methods this assay offers a higher sample throughput, excellent
      ruggedness and higher sensitivity. The limits of quantification for each
      enantiomer are 5.00 microg/L from 0.5 mL whole blood and 7.50 ng/g (ppb) using
      0.333 g brain tissue, respectively. Similar assay specifications have been
      derived for the two enantiomers. The method has been validated for the analysis
      of blood samples from low and high dosed preclinical pharmacokinetic and
      toxicokinetic studies, corresponding to two analytical working ranges like e.g.
      5.00 to 1000 microg/L and 200 to 40000 microg/L (0. 200 to 40.0 mg/L). For rat
      brain tissue the validated concentration range is 7.50 to 750 ng/g (ppb).

PMID- 10920366
TI  - Conformational studies of omega-conotoxins using electrospray mass spectrometry.
AB  - MVIIA and MVIIB omega-conotoxins were chosen to investigate the effect of
      experimental conditions on their conformations, because of the presence of three
      disulfide bridges in these toxins. There were no significant effects of ion
      source temperature, cone voltage, pH and percentage of cosolvent. We show that
      charge state distributions (CSDs) observed in their electrospray mass spectra are
      not a true reflection of the behaviour in the bulk solution because of
      electrostatic effects during the ion-evaporation process in the ion source. As a
      result it is not possible to deduce from the observed CSDs that some basic amino
      acids are hidden in the core of the peptide structure. This is important in view
      of the complementary finding that nearly all labile hydrogens are rapidly
      exchanged in deuterated solvents. The mass spectrometry results can be reconciled
      with results of NMR experiments and molecular calculations from the literature.

PMID- 10920379
TI  - Effect of luteinization stimulator and androgens on maturation of porcine
      granulosa cells.
AB  - Luteinization stimulator (LS), an intrafollicular compound of preovulatory (5-8
      mm) follicles, enhanced both basal and gonadotropins-stimulated production of
      progesterone (P4) by immature granulosa cells. The activity of LS was found in
      cell conditioned media (CM) obtained after the 3-day cultivation of preovulatory
      granulosa cells. Influence of testosterone, androstenedione and
      dihydrotestosterone on LS-enhanced P4 secretion was tested in culture of
      granulosa cells isolated from small follicles (1-3 mm). Small porcine granulosa
      cells were cultivated with or without LS in the presence of testosterone,
      androstenedione and dihydrotestosterone in concentration 10-10, 10-8 and 10-6
      mol.l-1. In the absence of LS, P4 production in the media with androgens was not
      significantly different from controls. LS alone significantly enhanced
      progesterone production by SGC. Androgens present in the culture media together
      with LS decreased a stimulatory influence of LS on P4 secretion. These data
      suggest a possible modulation of granulosa cells maturation by androgens.

PMID- 10920380
TI  - Statins: not just for cholesterol?

PMID- 10920381
TI  - The hypocretin/orexin story.
AB  - Newly described peptides, produced in neurons in the lateral hypothalamic area,
      have been shown to stimulate appetite and stereotypic behaviors associated with
      feeding. Discovered independently by two groups, the hypocretins/orexins
      stimulate autonomic function and have been shown to be physiological regulators
      of the arousal state. Neuroendocrine and metabolic effects of these peptides,
      some related to sleep-wakefulness and arousal state, are just now being
      discovered.

PMID- 10920382
TI  - Insights into the functions of type 1 (AT1) angiotensin II receptors provided by
      gene targeting.
AB  - The renin-angiotensin system (RAS) has a wide range of actions in biological
      processes ranging from development and reproduction to cardiovascular and renal
      functions. Most of these actions are mediated by the octapeptide hormone
      angiotensin II. The identified family of angiotensin II receptors is divided into
      two pharmacological classes: type 1 (AT1) and type 2 (AT2). The classically
      recognized actions of the RAS are primarily mediated by the AT1 subtype of
      angiotensin receptors, and these receptors are the targets of a new class of anti
      hypertensive agents. In recent years, our understanding of the physiological
      functions of AT1 receptors has been advanced through the use of gene-targeting
      technology. In this review, we will summarize the emerging picture of AT1
      receptor functions that has been provided by gene-targeting experiments.

PMID- 10920383
TI  - Genomic imprinting, uniparental disomy and foetal growth.
AB  - Genomic imprinting is an epigenetic phenomenon identified in the past 15 years.
      Thus, maternally imprinted genes are only expressed from the paternal allele and
      vice versa. The mechanism of imprinting is still far from certain, but most
      probably it involves differential methylation of specific sites in or near
      imprinted genes. Disrupted imprinting can lead to phenotypic changes, and an
      increasing number of resultant clinical disorders are being identified. Many of
      these conditions involve disordered growth and/or development, particularly
      prenatal.

PMID- 10920384
TI  - Steroid regulation of postembryonic development and reproduction in Drosophila.
AB  - Ecdysteroids trigger major developmental transitions in Drosophila, including
      larval molts and metamorphosis. Recent genetic studies strongly support a role
      for the Ecdysteroid receptor (EcR)/Ultraspiracle (USP) heterodimer as an
      ecdysteroid receptor at the onset of metamorphosis, functioning as both a
      transcriptional activator and repressor in vivo. Genetic analysis also indicates
      that USP, like its vertebrate homolog retinoid X receptor (RXR), might be
      involved in regulatory pathways independently of EcR. The ecdysteroid hierarchy
      was also shown recently to regulate Drosophila oogenesis and reproduction.

PMID- 10920385
TI  - The hepatocyte nuclear factor 3 (HNF3 or FOXA) family in metabolism.
AB  - The genes encoding hepatocyte nuclear factor 3 (HNF3) proteins play a pivotal
      role in the regulation of metabolism and in the differentiation of metabolic
      tissues such as the pancreas and liver. HNF3 transcription factors bind to cis
      regulatory elements in hundreds of genes encoding gluconeogenic and glycolytic
      enzymes, serum proteins and hormones. Genetic analysis in mice has shown that
      HNF3 beta is necessary for the development of the foregut endoderm, from which
      the liver and pancreas arise. HNF3 alpha is required for the full activation of
      glucagon in the pancreas, whereas HNF3 gamma induces the activation of
      gluconeogenic enzymes to prevent hypoglycemia during fasting.

PMID- 10920386
TI  - Adrenal autoimmunity: results and developments.
AB  - Autoimmune Addison's disease (autoimmune adrenalitis) often occurs in autoimmune
      polyendocrinopathy syndromes APS1 (APECED) and APS2. Although the genetic
      background and etiology of the two syndromes is remarkably different, they both
      result in a similar autoimmune destruction of the adrenal cortex. Recently, the
      defective gene in APS1, AIRE (autoimmune regulator) was identified, whereas in
      APS2, the major genetic factor remains to be found in the human major
      histocompatibility complex haplotype (HLA) region. In addition to the genetic
      factors, the recent findings in genetics and immunity leading to the pathogenesis
      of adrenal autoimmunity in polyendocrinopathy syndromes are discussed.

PMID- 10920388
TI  - Is Staphylococcus aureus an intracellular pathogen?

PMID- 10920387
TI  - Is Staphylococcus aureus an intracellular pathogen?

PMID- 10920389
TI  - Cell wall maintenance in fungi.

PMID- 10920390
TI  - UreI-mediated urea transport in Helicobacter pylori: an open and shut case?

PMID- 10920391
TI  - UreI-mediated urea transport in Helicobacter pylori: an open and shut case?

PMID- 10920392
TI  - Transcriptional analysis in Plasmodium falciparum.

PMID- 10920393
TI  - Renaming protein secretion in the gram-negative bacteria

PMID- 10920394
TI  - Bacterial type IV secretion: conjugation systems adapted to deliver effector
      molecules to host cells.
AB  - Several bacterial pathogens utilize conjugation machines to export effector
      molecules during infection. Such systems are members of the type IV or 'adapted
      conjugation' secretion family. The prototypical type IV system is the
      Agrobacterium tumefaciens T-DNA transfer machine, which delivers oncogenic
      nucleoprotein particles to plant cells. Other pathogens, including Bordetella
      pertussis, Legionella pneumophila, Brucellaspp. and Helicobacter pylori, use type
      IV machines to export effector proteins to the extracellular milieu or the
      mammalian cell cytosol.

PMID- 10920395
TI  - The T-pilus of Agrobacterium tumefaciens.
AB  - T-pilus biogenesis uses a conserved transmembrane nucleoprotein- and protein
      transport apparatus for the transport of cyclic T-pilin subunits to the
      Agrobacterium cell surface. T-pilin subunits are processed from full-length VirB2
      pro-pilin into a cyclized peptide, a rapid reaction that is Agrobacterium
      specific and can occur in the absence of Ti-plasmid genes.

PMID- 10920396
TI  - Microbial superantigens: from structure to function.
AB  - Superantigens are highly potent immune stimulators with a unique ability to
      interact simultaneously with MHC class II molecules and T cell receptors, forming
      a trimolecular complex that induces profound T-cell proliferation and massive
      cytokine production. Recent structural studies have provided a wealth of
      information regarding these complex interactions, and it is now emerging that,
      despite their common 3-D architecture, superantigens are able to crosslink MHC
      class II molecules and T cell receptors in a variety of ways.

PMID- 10920398
TI  - Prevalence of attention-deficit hyperactivity disorders in students. Comparison
      between DSM-IV and neuropsychological criteria.
AB  - Attention-deficit hyperactivity disorder (ADHD) is a common childhood condition,
      recognized as an important social-medical problem. The syndrome is characterized
      by motor system, perception, cognition and behavioral disturbances, compromising
      the learning of children with adequate intellectual potential. To investigate its
      prevalence in first grade pupils 484 children with DSM-IV diagnostic criteria and
      neuropsychological criteria were examined. The prevalence of ADHD was 18% when
      the diagnosis was made using DSM-IV criteria; 3.5% when neuropsychological
      criteria was used, including, in addition to behavioral and psychometric aspects,
      a discrepancy in the evolutionary neurological examination, and 3.9% when motor
      persistence was taken into account. The prevalence of ADHD was higher among older
      children (92.4 months) only when DSM-IV criteria were used. We conclude that the
      use of DSM-IV criteria probably overestimates the prevalence of ADHD, since it
      detects another behavioral disorders. In this context, they may be useful as
      screening, since they have adequate pre-testing performance.

PMID- 10920397
TI  - Selective nuclear export of viral mRNAs in influenza-virus-infected cells.
AB  - The NS1A protein of influenza A virus specifically inhibits the cellular
      machinery that processes the 3' ends of cellular pre-mRNAs by targeting two of
      the essential proteins of this machinery. Because the virus does not use this
      cellular machinery to synthesize the 3' poly(A) ends of viral mRNA, the nuclear
      export of cellular but not viral mRNAs is selectively inhibited.

PMID- 10920399
TI  - Cholesterol levels in panic disorder, generalized anxiety disorder and major
      depression.
AB  - Serum plasma total cholesterol levels were measured in 85 male or female
      outpatients with panic disorder (PD; N=41), generalized anxiety disorder (GAD;
      N=23) and major depression (MD; N=21) according to DSM-IV criteria. All the
      patients had a mean cholesterol level within the normal range; males (N=22) and
      females (N=63) had approximately the same serum cholesterol levels (p >.05). No
      significant differences in cholesterol levels emerged between PD, GAD and MD
      patient groups. Both female PD and female GAD subjects had a mean cholesterol
      level similar to their male counterparts (p>. 05). It is concluded that both
      Hayward and colleagues and Bajwa et al. findings could not be replicated by our
      study.

PMID- 10920400
TI  - Nervous system cancer mortality in an industrialized area of Brazil 1980-1993.
AB  - OBJECTIVES: The industrialization process and nervous system cancer (NSC)
      mortality in a urban region of Brazil. METHOD: From registries of the State
      System of Data Analysis Foundation (SEADE), 103 males deaths by NSC (ICD-9) in
      Baixada Santista (BS), from 1980 to 1993 were selected. Mortality ratios were
      calculated comparing the standardized mortality rate for ages over 10 years old
      (G1) and for the age group from 35 to 64 years old, in the industrialized and non
      industrialized areas in three periods: 1980-1993, 1980-86, 1987-93. RESULTS: A
      statiscally significant high mortality was observed in the industrialized area,
      for ages over 10 in all periods and only from 1980 to 1993 for ages from 34 to
      64. The highest mortality ratio occurred from 1980-86 for ages over 10 - 4.12 (CI
      1.79-9.42). CONCLUSION: High mortality was probably related to the environmental
      and occupational exposure to many organic and inorganic chemical substances,
      considered carcinogenics, such as aliphatic and aromatic hydrocarbons,
      organochlorinated, formaldehyde, nitrogenated compounds and heavy metals, found
      in the port and industrial complex. We discuss the importance of case-control
      studies in characterizing the association of these and other risk factors in the
      determination of NSC.

PMID- 10920401
TI  - Multimodal evoked potentials and the ovarian cycle in young ovulating women.
AB  - There is controversy over how hormonal conditions influence cerebral physiology.
      We studied pattern-shift visual evoked potentials (PS-VEP), brain stem auditory
      evoked potentials (BAEP) and short-latency somatosensory evoked potentials (SSEV)
      in 20 female volunteers at different phases of the menstrual cycle (estrogen
      phase, ovulatory day and progesterone phase). Statistical analysis showed
      decreased latencies for P100 (PS-VEP), N19 and P22 (SSEV) waves in the
      progesterone phase compared with the estrogen phase. There was no significant
      difference between the estrogen and the ovulation day values. Comparing the three
      above stages, there were no significant differences in the brainstem auditory
      evoked potentials. The reduction of the latencies of the potentials generated in
      multisynaptic circuits provides the first consistent neurophysiological basis for
      a tentative comprehension of human pre-menstrual syndrome.

PMID- 10920402
TI  - Simple, cost-effective technique for portable digital eletrocorticography.
AB  - We revised 16 patients submitted to epilepsy surgery using a new method of
      digital, real-time, portable electrocorticography. Patients were operated upon
      over a period of 28 months. There were no complications. The exam was useful in
      13 cases. The low installation and operational costs, the reliability and
      simplicity of the method, indicate it may be useful for defining the
      epileptogenic regions in a variety of circumstances, including surgery for
      tumors, vascular malformations, and other cortical lesions associated with
      seizure disorders.

PMID- 10920403
TI  - Naproxen sodium decreases migraine recurrence when administered with sumatriptan.
AB  - Forty to 78% of the patients using sumatriptan for the acute treatment of
      migraine may present recurrence at least occasionally. The concomitant use of a
      NSAID (nonsteroidal anti-inflammatory drug) has been recommended to decrease the
      recurrence rate. Sixty seven patients that treated successfully 8 migraine
      attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5
      attacks were studied prospectively. The patients received 100 mg of sumatriptan
      and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe
      migraine attacks. The recurrence rate, once at least 62.5% (5 out of 8 attacks),
      decreased to 14.2% (38 out of 268 attacks) with the combination of compounds
      (p<0.0001). We then studied two groups of 13 patients made randomicaly from the
      67 initially evaluated, that were given sumatriptan 100 mg plus naproxen sodium
      550 mg or placebo, in a double-blind design, to treat 3 other consecutive
      migraine attacks. Each group of patients treated 39 attacks. The recurrence among
      the patients taking sumatriptan plus placebo was 59% (23 out of 39 attacks) and
      the recurrence presented by the group taking sumatriptan plus naproxen was 25.5%
      (10 out of 39 attacks) (p<0.0003). We concluded that the combination of
      sumatriptan plus naproxen sodium decreases significantly migraine recurrence
      presented by patients taking sumatriptan alone.

PMID- 10920404
TI  - [Migraine prevalence and impact in employees of the clinical hospital of the
      medical school of Ribeirao Preto-USP].
AB  - Headache is a common symptom in the population, with a life prevalence around
      90%. It results in an important impact in the life quality of sufferers. The aim
      of this study is to evaluate the prevalence of migraine among employees of an
      university hospital (HC), as well as to measure the headache intensity,
      interference and impact in the daily activities. A total of 1890 employees had
      answered to a questionnaire which made possible to carry out diagnosis of
      migraine. Life prevalence of this headache type was 30. 4%. Pain was considered
      intense, most of the time, by 86% of the migraneurs. It was verified an important
      impact in the daily life aspects as much during as between the headache attacks.
      It can be concluded that migraine represents a public health problem among the HC
      employees. Because migraine brings about an important impact in the life quality
      of those workers, it is possible that a reduction of working capacity with
      considerable economic burden exists. This problem deserves, thus, special
      attention, through a better diagnostic and treatment.

PMID- 10920405
TI  - [Chronic daily headache: clinical presentation].
AB  - Chronic daily headache (CDH) represents a group of any headache disorder that
      occurs on a daily or near daily basis, for longer than 6 months. Even though it
      is a common problem, it is not a well defined disorder, resulting in
      controversies regarding its identification, description and approach. Three
      hundred patients, 232 women and 68 men, ages 16 to 86 (mean 38 years old for the
      women and 42 for the men), attending a headache center and fulfilling the
      proposed criteria for CDH (Silberstein et al.) and presenting headache 28 days
      per month were retrospectively studied. The clinical features allowed the primary
      headache diagnosis, before the transformation into daily presentation as:
      transformed migraine (TM ) in 271 patients (90,3%), chronic tension-type headache
      (CTTH) in 26 patients (8,7%) and new daily persistent headache (NDPH) in 3
      patients (1%). Among the TM patients, the most observed presentation was pressure
      or tightening, bilateral fronto-temporal, moderate non-continuous headache, with
      a progressive onset. The association with nausea and phonophobia was demonstrated
      in 60% and 32% of the patients respectively. The association with photophobia and
      sleep disturbances, as well as the occurrence of intermittent headache attacks,
      was different among male and female patients. With regard to the CTTH patients,
      pressure or tightening, bilateral fronto-temporal, moderate non-continuous
      headache, with sleep disturbances and no associated symptoms, was the predominant
      presentation.

PMID- 10920406
TI  - [Interferon beta 1-a in multiple sclerosis: 1-year experience in 62 patients].
AB  - We report the results of a trial of interferon beta 1-a in 62 ambulatory patients
      with relapsing-remitting multiple sclerosis. Entry criteria included EDSS of 0 to
      5.5 and at least two exacerbations in the previous 2 years. The patients received
      3 million international units by subcutaneous injections three times a week. The
      end points were differences in exacerbation rate and treatment effect on disease
      progression. The annual exacerbation rate for patients that did not take the
      interferon beta 1-a was 1.32 and for the patients under medication 0.63. The EDSS
      score in patients that did not take the mediaction was 4.7 and 2.0 for the
      patients with interferon beta 1-a. Interferon beta 1-a was well tolerated and 85%
      of patients completed 1 year treatment.

PMID- 10920407
TI  - [Multiple sclerosis: descriptive study of its clinical forms in 302 cases].
AB  - Multiple sclerosis (MS) is one of the most common causes of chronic neurologic
      disability in young adults. We evaluate, through retrospective study, the
      epidemiological characteristics, the manifestations ways, the clinical
      manifestations, the evolution and the level of physical disability of MS in 302
      patients. The average patients age was 37.7 and the relation between genders was
      3.13F:1M. The average age at the beginning of MS was 29.6; 283 patients were
      white (94%), 15 patients were black (5%) and 4 patients were yellow; 220 patients
      (72%) presented relapsing-remmiting clinical form; 82 patients (28%) presented
      the progressive form (50% secondary form and 50% primarily progressive form). The
      most common initial symptoms were sensitive (31.7%) and optical (26.8%). The most
      common evolutive symptoms were pyramidal (72.5%) and of the spinal cord (64.9%).
      The average of the final EDSS was 3.37 and final NRS was 85.17. The index of the
      annual outbreak was 0.45. Our findings coincide to the ones in the worldwide
      literature, however it is important to point out that 60 patients (19.8%)
      presented benign MS of prognostic value.

PMID- 10920409
TI  - [Fatigue in multiple sclerosis relapsing-remitting form].
AB  - In 95 patients with the remitting-relapsing form of multiple sclerosis we
      investigated fatigue. All of them were evaluated with the Fatigue Severity Scale
      and we found it in 64 patients (67.4%). Gender, age, depression and fuctional
      incapacity was not predictive of fatigue occurrence, while anxiety and time of
      disease seems to be correlated with it. When we analysed the fatigue severity, a
      correlation between the EDSS and the increasing fatigue severity was found.

PMID- 10920408
TI  - [Fatigue and multiple sclerosis: preliminary study of 15 patients with self
      reported scales].
AB  - Fatigue is a common and disabiling symptom in multiple sclerosis but is poorly
      understood. Self-report measures are designed to capture the patient's subjective
      sense of fatigue. We applied three scales in 15 patients with MS. Nine of them
      reported fatigue. The scores were high in all of these patients. We conclude that
      these scales must be used in assemble, to evaluate this symptom. Also, fatigue a
      very important symptom in multiple sclerosis patients.

PMID- 10920410
TI  - [Assessment through P300 of epileptic and non-epileptic children and school
      performance].
AB  - Learning disability is common in epileptic children. Epilepsy has been associated
      with disorders of intelligence. Cognitive potential (P300) is considered to be a
      clinical aid in the neurophysiological measurement of the cognitive process.
      Ninety-nine children between the ages of 10 years and 11 years and 11 months
      formed our sample, with good and poor school performance. Group I, non-epileptic,
      had 64 children of whom 32 had good and 32 poor school performance. Group II,
      epileptic, had 35 children, of whom 21 had good and 15 poor school performance.
      No significant difference in P300 latency was found between Groups I and II. When
      groups were stratified based on school performance, Group I children with good
      school performance had P300 latency of 336 ms, while the ones with poor school
      performance had latency of 382 ms. Group II children with good school performance
      had P300 latency of 363, while the ones with poor school performance had latency
      of 400 ms. There was a statistically significant difference between the non
      epileptic children with good school performance and the children with poor school
      performance, epileptic or not.

PMID- 10920411
TI  - [Microsurgical anatomy of sellar region in cadavers using a photographic
      technique with fluorescein].
AB  - The microsurgical anatomy of sellar regions in 20 cadavers with a 12 hours
      maximum post mortem was studied. Fluorescein was used as contrast for vascular
      anatomy examination. The use of fresh specimen and fluorescein had the objective
      of avoiding any distortion of normal anatomy. The drug was diluted with water or,
      in order to have more consistency, in gel for ultrasonography. Contrast injection
      was made into the internal carotid artery and photographs were taken with three
      different kinds of lighting: 1) only with Wood's lamp; 2) Wood's lamp and normal
      white light; 3) only with white light. Lighting only with Wood's lamp showed more
      contrast. After measurement, data often showed discrepancies with other authors'
      data. The photographic technique with fluorescein is simple and accessible; the
      drug showed high quality as a vascular contrast for neuroanatomic research.

PMID- 10920412
TI  - [Lack of gender effect on familial schizophrenia. A Brazilian study].
AB  - Epidemiological studies on schizophrenia have showed different age at onset
      between gender, in which male schizophrenics present symptoms earlier than
      females. However this gender effect is not observed within familial
      schizophrenia. The present study investigates the age at onset in 31 RDC
      schizophrenics from 13 Brazilian families. No differences in age at onset were
      found between gender, confirming previous studies in other populations. This
      result may indicate genetic influences on age at onset in a subgroup of patients
      affected by schizophrenia and can be explored by molecular genetic studies.

PMID- 10920413
TI  - [Primary intracerebral hemorrhage. Retrospective study of 72 operated cases].
AB  - We analysed 72 cases of primary intracranial hemorrhage surgically treated from
      1970 to 1999. The hemorrhages were diagnosed by computerized axial tomography in
      52 patients. Most hematomas were situated in the cerebral hemispheres (30 percent
      in thalamus-basal ganglia region and 50 percent in the subcortical matter). There
      were 10 patients with cerebellar hemorrhage. Hypertension (based in blood
      pressure recordings in the hospital and history) was found in 24 patients (33
      percent). The most frequent findings were coma, intracranial hypertension and
      hemimotor deficit. The death rate registered was 27.7 percent; however, it was
      found a significant difference in the mortality index when considering the 70-79
      decade (62.7 percent) and the 90-99 decade (20.7 percent). A critical analysis
      was made about depth hematomas, consciousness state and intracranial hypertension
      with herniation related to surgical procedure.

PMID- 10920414
TI  - [Choroid plexus carcinoma: report of 15 cases].
AB  - Choroid plexus carcinoma (CPC) are rare central nervous system tumours derived
      from choroid plexus epithelium, affecting mainly children under 3 years of age.
      We present a clinical, epidemiological and histopathological study of 15 cases of
      CPC. Ten patients were male. Age ranged from 4 months to 21 years (mean=3,4). The
      lateral ventricles were affected in 73,3% of cases. Main symptom were:
      hydrocephalus (62.5%), intracranial hypertension (25%) and convulsion (12.5%).
      The patients were treated by surgery with partial resection in 75% of cases and
      total resection in 25%. There was one death due to surgical complication, 85.7%
      of patients had recurrence of tumours with mean survival rate of 13.6% months
      after diagnosis. Only one patient remain alive 5 years after initial treatment.
      These results support the poor prognosis and high mortality rate of CPC.

PMID- 10920415
TI  - [Infantile spasms: experience in 13 cases].
AB  - Infantile spasms are typical crisis found in the childhood being a serious
      pathology with an obscure prognosis. We present the experience of the Service of
      Neuropediatrics in the Pediatric General Center, Belo Horizonte - Brasil, during
      the year of 1997, with a review of the literature about. After appropriate
      propaedeutics, were found 12 cases considered symptomatics and 1 case
      cryptogenic. All these cases were treated with ACTH during 6 weeks associated
      with oral antiepileptic drugs in mono or polytherapy for maintenance. We had
      excellent results using ACTH at the beginning of the treatment, obtaining good
      results in all of the cases with some side effects that were not important enough
      to interrupt the treatment. However, there was a recurrence rate of 55% and
      vigabatrin was used as second option, controlling 4 of the 5 cases. All the cases
      showed retardation of the neuropsychomotor development.

PMID- 10920416
TI  - Cluster-tic syndrome: report of five new cases.
AB  - The so-called short lasting primary headaches include heterogenic entities that
      can be divided between those without pronounced autonomic activation and those
      where this activation is evident, which includes the cluster-tic syndrome. We
      report five new cases with age closer to the trigeminal neuralgia's one, and
      concomitance of cluster headache and trigeminal neuralgia, which is less frequent
      in the literature. We also discuss briefly the pathophysiology of these clinical
      entities, suggesting that the trigeminus nerve is a common pathway of pain
      manifestation.

PMID- 10920417
TI  - [Psychogenic dystonia: report of 2 cases].
AB  - Movement disorders have rarely been the result of psychiatric disturbances.
      Psychogenic dystonia is caracterized by inconsistent findings, a known
      precipitant factor, onset in legs, pain, multiple somatizations and incongruent
      association with other movement disorders. We report two patients with clinically
      established psychogenic dystonia. Patient 1: a female that presented sudden loss
      of strength in her four limbs; she developed feet dystonia, alternant
      laterocollis, generalized and irregular tremor, and limb hypertonia that
      disappeared with distraction; psychological examination showed severe depression,
      hypochondria and obsessive disorder. Patient 2: a female that presented with
      irregular limb tremors that disappeared with distraction and left foot dystonia
      nine years ago; she gradually lost her walk capacity; she complained pain in
      lumbar area and in her left limb, psychological examination showed infantile
      behaviour, low frustration tolerance, impulsivity and self-aggression. Their
      complementary exams showed no alterations and they had no response to specific
      pharmacological treatment. Dystonia is rarely psychogenic, but this etiology is
      suggested when clinical characteristics are inconsistent and incongrous with a
      classical disorder. It should be part of differential diagnosis when appears in
      association with other somatization or psychiatric disorders.

PMID- 10920419
TI  - De novo psychogenic seizures after epilepsy surgery: case report.
AB  - The occurrence of de novo psychogenic seizures after epilepsy surgery is rare,
      and is estimated in 1.8% to 3.6%. Seizures after epilepsy surgery should be
      carefully evaluated, and de novo psychogenic seizures should be considered
      especially when there is a change in the ictal semiology. We report a patient
      with de novo psychogenic seizures after anterior temporal lobe removal for
      refractory temporal lobe epilepsy. Once psychogenic seizures were diagnosed and
      psychiatric treatment was started, seizures stopped.

PMID- 10920418
TI  - Neuropsychological sequelae in Kleine-Levin syndrome: case report.
AB  - Kleine-Levin syndrome is characterized by periodic hypersomnia, hyperphagia,
      sexual disinhibitions and behavioral disturbances. The prognosis is generally
      benign, with normal cognitive and social functions after the episodes. We
      describe a typical case of Kleine-Levin syndrome associated with apparent
      academic decline, neuropsychological sequelae and personality alterations after
      the second episode of the illness. Further research in the natural history of
      Kleine-Levin syndrome is needed, for example, to determine whether early
      intervention would improve long-term prognosis.

PMID- 10920420
TI  - [Neurocysticercosis and Lennox-Gastaut syndrome: case report].
AB  - Report of a girl with the epileptic, hydrocephalic and encephalitic form of
      neurocysticercosis, diagnosed by cerebrospinal fluid and computed tomography
      exams, during her second year of life and an evolution with multiple types of
      seizures, prolonged periods of intracranial hypertension due to obstruction in
      the ventriculoperitoneal shunt, psychomotor regression and blindness until she
      was 10 years old, when the Lennox-Gastaut syndrome was diagnosed. Nowadays the
      patient is 16 years old and presents complex partial seizures with automatism not
      completely controlled with clobazan and oxcarbazepine, associated to left spastic
      hemiparesis, universal hyperreflexia, psychomotor agitation, self-mutilation,
      amaurosis and severe mental retardation. The association between
      neurocysticercosis and Lennox-Gastaut syndrome was first described in 1973 by
      Frochtengarten & Scarante in a Brazilian girl with a similar clinical picture.

PMID- 10920421
TI  - [Interictal personality syndrome in non-dominant temporal lobe epilepsy: case
      report].
AB  - The syndrome of interictal personality in non-dominant temporal lobe epilepsy
      consists of hyposexuality, hyperreligiosity, humorlessness and hypergraphia. Its
      notification, in 1974, was followed by an extensive search for these traits in
      broad epileptic populations. Nevertheless, these statistical studies failed to
      match this syndrome in general temporal lobe epileptics, and its existence became
      then target of doubt. We report the case of a 35 year-old man presenting partial
      complex epilepsy, whose singularity lies in his sophisticated drawing abilities.
      The large amount of buildings and houses he paints expresses his hypergraphia. He
      also presents hyposexuality and hyperreligiosity. MRI shows right mesial temporal
      sclerosis. Temporal hyperconnection, caused by a basal temporal irritative focus,
      is the most probable pathophysiological mechanism. Epileptic fits can be
      controlled in the majority of cases. However, behavioural symptoms usually do not
      respond to pharmacological approach or psychotherapy.

PMID- 10920422
TI  - [Severe Raynaud's phenomenon associated with interferon-beta therapy for multiple
      sclerosis: case report].
AB  - Interferon-beta (IFN-beta) is administered for treatment of multiple sclerosis
      (MS). We report on a woman with MS who presented with severe Raynaud's
      phenomenon, livedo-reticularis and digital necrosis two weeks after beginning
      therapy with IFN-beta. Symptoms improved after the IFN-beta was discontinued and
      anticoagulation associated with cyclophosphamide and corticoid were introduced.
      Raynaud's phenomenon is probably a side effect of IFN-beta therapy for multiple
      sclerosis.

PMID- 10920423
TI  - [Procedures to improve daily activities performance in individuals with cerebral
      anoxia: case report].
AB  - OBJECTIVE: To present a rehabilitation case study; procedures to improve the
      performance on daily activities were used by the caregiver. PATIENT: Cerebral
      anoxia due to cardiac arrest. He presented memory deficits for both visual and
      verbal material, temporal disorientation, abulia, psychomotor slowing and
      bradypsychism. METHODS: daily activities were developed in fixed hours; calendar
      was presented 3 times a day; daily walks were performed; self-care activities
      were performed by the patient with short verbal commands and cues from the
      caregiver. RESULTS: We observed improvement on initiative and autonomy for daily
      activities, attention, temporal orientation and bradypsychism. There was also
      reduction on response time. CONCLUSIONS: Behavioral control strategies result on
      improvement for patients and their family although limit their routine.
      Behavioral control strategy promotes learning through the preserved implicit
      memory mechanism and results on enhancement at patient's autonomy at home.

PMID- 10920424
TI  - [Change in the biological pattern of migraine with aura after the use of
      tetrabenazine: case report].
AB  - The influence of the dopaminergic system on the pathophysiology of migraine has
      been suggested as a result of recent genetic discoveries. A possible hyper
      reactivity of the dopaminergic receptors DRD2 reinforced the evidence regarding
      this. We describe a 31 years-old male patient affected by a generalized dystonia
      secondary to perinatal hypoxia. At age 16, the patient started having headache
      crises that met the criteria for migraine with aura. After three years of
      treatment for dystonia with tetrabenazine, a clear reduction in the frequency,
      intensity and duration of the crises was perceived. During two periods longer
      than two months, the interruption of the treatment with tetrabenazine brought
      about an aggravation of the migraine crises. We present this case as being the
      first description in the literature showing the beneficial effects of
      tetrabenazine, a blocker of dopaminergic receptors, on the behavior of migraine
      with aura.

PMID- 10920425
TI  - [Intracranial tuberculomas developing during treatment of pulmonary tuberculosis:
      case report].
AB  - The classical presentation of neurotuberculosis is meningitis. Intracranial
      tuberculomas are a rare manifestation of neurotuberculosis and are due to
      hematogenous dissemination of distant focuses of Mycobacterium tuberculosis
      infection. Around 1% of patients with central nervous system tuberculosis develop
      intracranial tuberculomas some weeks or months after the beginning of the
      specific treatment with tuberculostatic chemotherapy. The involution of the
      lesions is slow and does not mean drug resistance nor lack of adequate treatment.
      We describe the case, diagnosed and treated at the 25th Infirmary of Santa Casa
      da Misericordia do Rio de Janeiro, of an immunocompetent male patient who
      developed meningitis and multiple intracranial tuberculomas during the specific
      treatment of miliary tuberculosis. The literature is revised and the diagnosis,
      treatment and possible immunological mechanisms are discussed.

PMID- 10920426
TI  - [Dementia caused by neurosyphilis: clinical and neuropsychological follow-up of a
      patient].
AB  - Dementia is one of the manifestations of late syphilis and it is characterized by
      cognitive deterioration and behaviour disturbances. We report on a male patient
      with cognitive decline, behaviour disorder, hyperactivity, hallucinations, short
      term memory and Argyll Robertson pupils due to neurosyphilis. Minimental state
      test (MST) was 16. Cerebrospinal fluid (CSF) protein concentration was 82 mg/dl,
      CSF-leucocyte count 128 cells/mm3 (98% mononuclear cells), CSF-VDRL 1:4, and CSF
      T.pallidum haemaglutination assay 1:2560. MRI showed no cerebral alteration, but
      SPECT revealed left fronto-temporal hypocaptation. He received intravenous
      penicillin. MST done 3 months after the treatment scored 22. A new spinal tap
      showed normal CSF. Neurosyphilis should be part of the differential diagnosis of
      every patient showing cognitive deterioration and behaviour disturbances. During
      follow-up, MMS is an useful instrument to ++measure cognitive decline and
      response to treatment.

PMID- 10920427
TI  - Neuroprotection, excitotoxicity and NMDA antagonists.
AB  - PURPOSE: To analyze the main aspects of neuroprotection and excitotoxicity.
      DISCUSSION: This is a significant theory on the pathophysiology of cerebral
      ischemia; it is based on the release of excitatory aminoacid (EAA), mainly
      glutamate. The sequence starts with a decrease of the blood flow and ends in
      neuronal death. The main stages of this reaction are herein presented and
      discussed. An in depth study of the effects of the excessive intracellular
      calcium is undertaken. Neuroprotectors (NP) are a group of drugs that reduce the
      excitotoxicity, opposing the excessive release of EAA and its intracellular
      effects. Neuroprotectors represent a rational approach to stroke treatment and
      offer a number of potential advantages. They prevent or limit ischemia-induced
      damage. CONCLUSION: There are many experimental and clinical NP trials. A minimum
      of 800 trials are currently under study worldwide. The most important NP
      subgroups are: N-methyl D-aspartate (NMDA) antagonists, gamma-amino butyric acid
      (GABA) agonists, amino-hydroxy-methyl-isoxalone propionic acid (AMPA)
      antagonists, reducers of intracellular Ca++ inhibitors of nitric oxide modulation
      pathway free radicals scavengers, sodium channel antagonists, glutamate release
      inhibitor, growth factors, hypothermia and potassium channel activators.

PMID- 10920428
TI  - Mapping cancer, cardiovascular and malaria research in Brazil.
AB  - This paper presents performance indicators for the Brazilian cancer,
      cardiovascular and malaria research areas from 1981 to 1995. The data show an
      increasing number of papers since 1981 and author numbers indicate a continuous
      growth of the scientific community and suggest an expected impact of scientific
      activity on biomedical education. The data also characterize cardiovascular
      research as a well-established area and cancer research as a faster growing
      consolidating field. The 1989-1994 share of Brazilian articles among world
      publications shows a growing trend for the cancer (1.61) and cardiovascular
      (1.59) areas, and a decrease for the malaria area (0. 89). The burden of the
      three diseases on society is contrasted by the small number of consolidated
      Brazilian research groups, and a questionable balance of thematic activity,
      especially with regard to malaria. Brazilian periodicals play an important role
      in increasing the international visibility of science produced in the country.
      Cancer and cardiovascular research is strongly concentrated in the Southeastern
      and in Southern regions of Brazil, especially in Sao Paulo (at least one address
      from Sao Paulo in 64.5% of the 962 cancer articles and in 66.9% of the 2250
      cardiovascular articles, the second state being Rio de Janeiro with at least one
      address in 14.1 and 11% of those articles, respectively). Malaria research (468
      articles) is more evenly distributed across the country, following the pattern of
      the endemic distribution of the disease. Surveying these national indicator
      trends can be useful to establish policies in the decision process about health
      sciences, medical education and public health.

PMID- 10920429
TI  - Biology and clinical utilization of mesenchymal progenitor cells.
AB  - Within the complex cellular arrangement found in the bone marrow stroma there
      exists a subset of nonhematopoietic cells referred to as mesenchymal progenitor
      cells (MPC). These cells can be expanded ex vivo and induced, either in vitro or
      in vivo, to terminally differentiate into at least seven types of cells:
      osteocytes, chondrocytes, adipocytes, tenocytes, myotubes, astrocytes and
      hematopoietic-supporting stroma. This broad multipotentiality, the feasibility to
      obtain MPC from bone marrow, cord and peripheral blood and their
      transplantability support the impact that the use of MPC will have in clinical
      settings. However, a number of fundamental questions about the cellular and
      molecular biology of MPC still need to be resolved before these cells can be used
      for safe and effective cell and gene therapies intended to replace, repair or
      enhance the physiological function of the mesenchymal and/or hematopoietic
      systems.

PMID- 10920430
TI  - Alterations in proteins of bone marrow extracellular matrix in undernourished
      mice.
AB  - The objective of the present study was to determine the effect of protein
      malnutrition on the glycoprotein content of bone marrow extracellular matrix
      (ECM). Two-month-old male Swiss mice were submitted to protein malnutrition with
      a low-protein diet containing 4% casein as compared to 20% casein in the control
      diet. When the experimental group had attained a 20% loss of their original body
      weight, we extracted the ECM proteins from bone marrow with PBS buffer, and
      analyzed ECM samples by SDS-PAGE (7.5%) and ECL Western blotting. Quantitative
      differences were observed between control and experimental groups. Bone marrow
      ECM from undernourished mice had greater amounts of extractable fibronectin (1.6
      fold increase) and laminin (4.8-fold increase) when compared to the control
      group. These results suggest an association between fluctuations in the
      composition of the hematopoietic microenvironment and altered hematopoiesis
      observed in undernourished mice.

PMID- 10920431
TI  - Characterization of a methionine-rich protein from the seeds of Cereus jamacaru
      mill. (Cactaceae).
AB  - We describe here the isolation and characterization of a major albumin from the
      seeds of Cereus jamacaru (Cactaceae), to which we gave the trivial name of
      cactin. This protein has a molecular mass of 11.3 kDa and is formed by a light
      chain (3.67 kDa) and a heavy chain (7.63 kDa). This protein was isolated using a
      combination of gel filtration chromatography and reverse-phase HPLC. The amino
      acid composition of cactin was determined and found to resemble that of the 2S
      seed reserve protein from the Brazil nut, a protein remarkable for its high
      methionine content. The usefulness of cactin as a molecular marker in the
      taxonomy of the Cactaceae is discussed.

PMID- 10920432
TI  - Properties of a constitutive alkaline phosphatase from strain 74A of the mold
      Neurospora crassa.
AB  - A constitutive alkaline phosphatase was purified to apparent homogeneity as
      determined by polyacrylamide gel electrophoresis from mycelia of the wild strain
      74A of the mold Neurospora crassa, after growth on acetate and in the presence of
      saturating amounts of inorganic phosphate (Pi) for 72 h at 30 degrees C. The
      molecular mass was 58 kDa and 56 kDa as determined by exclusion chromatography
      and SDS-PAGE, respectively. This monomeric enzyme shows an apparent optimum pH
      ranging from 9.5 to 10.5 and Michaelis kinetics for the hydrolysis of p
      nitrophenyl phosphate (the K(m) and Hill coefficient values were 0.35 mM and
      1.01, respectively), alpha-naphthyl phosphate (the K(m) and Hill coefficient
      values were 0.44 mM and 0.97, respectively), beta-glycerol phosphate (the K(m)
      and Hill coefficient values were 2.46 mM and 1.01, respectively) and L-histidinol
      phosphate (the K(m) and Hill coefficient values were 0.47 mM and 0.94,
      respectively) at pH 8.9. The purified enzyme is activated by Mg(2+), Zn(2+) and
      Tris-HCl buffer, and is inhibited by Be(2+), histidine and EDTA. Also, 0.3 M Tris
      HCl buffer protected the purified enzyme against heat inactivation at 70 degrees
      C (half-life of 19.0 min, k = 0.036 min(-1)) as compared to 0.3 M CHES (half-life
      of 2.3 min, k = 0.392 min(-1)) in the same experiment.

PMID- 10920433
TI  - Catecholamine response to exercise in individuals with different levels of
      paraplegia.
AB  - The purpose of this study was to investigate the effect of the level of injury on
      the serum level of norepinephrine (Nor) and epinephrine (Epi) at rest and after
      maximal exercise in individuals with paraplegia. Twenty-six male spinal cord
      injured subjects with complete paraplegia for at least 9 months were divided into
      two groups of 13 subjects each according to the level of injury, i.e., T1-T6 and
      T7-T12. Serum Nor and Epi concentrations were measured by HPLC-ECD, at rest (PRE)
      and immediately after a maximal ergospirometric test (POST). Statistical analysis
      was performed using parametric and non-parametric tests. Maximal heart rate, peak
      oxygen uptake, and PRE and POST Nor were lower in the T1-T6 than in the T7-T12
      group (166 +/- 28 vs 188 +/- 10 bpm; 18.0 +/- 6.0 vs 25.8 +/- 4.1 ml kg(-1) min(
      1); 0.54 +/- 0.26 vs 0.99 +/- 0.47 nM; 1.48 +/- 1. 65 vs 3.07 +/- 1.44 nM). Both
      groups presented a significant increase in Nor level after exercise, while only
      the T7-T12 group showed a significant increase in Epi after exercise (T1-T6: 0.98
      +/- 0.72 vs 1.11 +/- 1.19 nM; T7-T12: 1.24 +/- 1.02 vs 1.89 +/- 1.57 nM). These
      data show that individuals with paraplegia above T6 have an attentuated
      catecholamine release at rest and response to exercise as compared to subjects
      with injuries below T6, which might prevent a better exercise performance in the
      former group.

PMID- 10920434
TI  - Abnormal proliferative response of the carotid artery of spontaneously
      hypertensive rats after angioplasty may be related to the depolarized state of
      its smooth muscle cells.
AB  - Hypertension is one of the major precursors of atherosclerotic vascular disease,
      and vascular smooth muscle abnormal cell replication is a key feature of plaque
      formation. The present study was conducted to examine the relationship between
      hypertension and smooth muscle cell proliferation after balloon injury and to
      correlate neointima formation with resting membrane potential of uninjured smooth
      muscle cells, since it has been suggested that altered vascular function in
      hypertension may be related to the resetting of the resting membrane potential in
      spontaneously hypertensive rats (SHR). Neointima formation was induced by balloon
      injury to the carotid arteries of SHR and renovascular hypertensive rats (1K-1C),
      as well as in their normotensive controls, i.e., Wistar Kyoto (WKY) and normal
      Wistar (NWR) rats. After 14 days the animals were killed and the carotid arteries
      were submitted to histomorphometric and immunohistochemical analyses. Resting
      membrane potential measurements showed that uninjured carotid arteries from SHR
      smooth muscle cells were significantly depolarized (-46.5 +/- 1.9 mV) compared to
      NWR (-69 +/- 1.4 mV), NWR 1K-1C (-60.8 +/- 1.6 mV), WKY (-67.1 +/- 3.2 mV) and
      WKY 1K-1C (-56.9 +/- 1.2 mV). The SHR arteries responded to balloon injury with
      an enhanced neointima formation (neo/media = 3.97 +/- 0.86) when compared to
      arteries of all the other groups (NWR 0.93 +/- 0.65, NWR 1K-1C 1.24 +/- 0.45, WKY
      1.22 +/- 0.32, WKY 1K-1C 1.15 +/- 0.74). Our results indicate that the increased
      fibroproliferative response observed in SHR is not related to the hypertensive
      state but could be associated with the resetting of the carotid smooth muscle
      cell resting membrane potential to a more depolarized state.

PMID- 10920435
TI  - alpha-Tocopherol enhances tumour growth inhibition by cis-dichlorodiammine
      platinum (II).
AB  - Present studies indicate that alpha-tocopherol enhances the efficacy of cisplatin
      as demonstrated by inoculation of Dalton's lymphoma cells incubated with either
      cisplatin (5 or 10 microg/ml) alone or cisplatin + alpha-tocopherol (25 or 50
      microg/ml) into C3H/He mice. Tumour cells (3 x 10(6) cells/mouse) incubated with
      cisplatin grow slowly in syngeneic mice as indicated by the late appearance of
      tumour. However, mice failed to develop tumour when inoculated with tumour cells
      incubated with cisplatin + alpha-tocopherol. When the animals were challenged
      with tumour cells (3 x 10(6) cells/mouse) on the 15th day after the initial
      inoculation, 30-50% survived more than 60 days, with 10% tumour-free survivors
      being observed in some groups. Antitumour activity was higher in mice receiving
      lymphoma cells (3 x 10(6) cells/mouse) preincubated with cisplatin + alpha
      tocopherol compared to cisplatin alone. Tumour-bearing mice receiving cisplatin
      in combination with different concentrations of alpha-tocopherol exhibited
      significantly higher (P<0.001) intratumour platinum content (123-306%) but
      without any change in the kidney platinum content as compared to those receiving
      cisplatin (5 or 10 microg/ml) alone. Enhancement of cisplatin-induced tumour
      growth inhibition is probably due to the modulation of tumour cell membrane
      permeability by alpha-tocopherol. alpha-Tocopherol might increase the influx of
      cisplatin into tumour cells, causing the DNA repair machinery to be less
      efficient due to increased efficiency of adduct formation in the DNA molecule.
      This effect of alpha-tocopherol can render cisplatin more effective as an
      antitumour agent.

PMID- 10920436
TI  - A priori estimation of accuracy and of the number of wells to be employed in
      limiting dilution assays.
AB  - The use of limiting dilution assay (LDA) for assessing the frequency of
      responders in a cell population is a method extensively used by immunologists. A
      series of studies addressing the statistical method of choice in an LDA have been
      published. However, none of these studies has addressed the point of how many
      wells should be employed in a given assay. The objective of this study was to
      demonstrate how a researcher can predict the number of wells that should be
      employed in order to obtain results with a given accuracy, and, therefore, to
      help in choosing a better experimental design to fulfill one's expectations. We
      present the rationale underlying the expected relative error computation based on
      simple binomial distributions. A series of simulated in machina experiments were
      performed to test the validity of the a priori computation of expected errors,
      thus confirming the predictions. The step-by-step procedure of the relative error
      estimation is given. We also discuss the constraints under which an LDA must be
      performed.

PMID- 10920437
TI  - Chronic intrathecal cannulation enhances nociceptive responses in rats.
AB  - The influence of a chronically implanted spinal cannula on the nociceptive
      response induced by mechanical, chemical or thermal stimuli was evaluated. The
      hyperalgesia in response to mechanical stimulation induced by carrageenin or
      prostaglandin E2 (PGE2) was significantly increased in cannulated (Cn) rats,
      compared with naive (Nv) or sham-operated (Sh) rats. Only Cn animals presented an
      enhanced nociceptive response in the first phase of the formalin test when low
      doses were used (0.3 and 1%). The withdrawal latency to thermal stimulation of a
      paw inflamed by carrageenin was significantly reduced in Cn rats but not in Nv or
      Sh rats. In contrast to Nv and Sh rats, injection in Cn animals of a standard non
      steroid anti-inflammatory drug, indomethacin, either intraperitoneally or into
      the spinal cord via an implanted cannula or by direct puncture of the intrathecal
      space significantly blocked the intensity of the hyperalgesia induced by PGE2.
      Cannulated animals treated with indomethacin also showed a significant inhibition
      of second phase formalin-induced paw flinches. Histopathological analysis of the
      spinal cord showed an increased frequency of mononuclear inflammatory cells in
      the Cn groups. Thus, the presence of a chronically implanted cannula seems to
      cause nociceptive spinal sensitization to mechanical, chemical and thermal
      stimulation, which can be blocked by indomethacin, thus suggesting that it may
      result from the spinal release of prostaglandins due to an ongoing mild
      inflammation.

PMID- 10920438
TI  - Anti-hyperalgesic effect of electroacupuncture in a model of post-incisional pain
      in rats.
AB  - Electroacupuncture has been proposed to be a low cost and practical method that
      allows effective pain management with minimal collateral effects. In this study
      we have examined the effect of electroacupuncture against the hyperalgesia
      developed in a model of post-incisional pain in rats. A 1-cm longitudinal
      incision was made through the skin and fascia of the plantar region of the animal
      hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the
      surgery with von Frey filaments. The tension threshold was reduced from 75 g
      (upper limit of the test) to 1.36 +/- 0.36 g (mean +/- SEM) in control rats. It
      is shown that a 15-min period of electroacupuncture applied 120 min after surgery
      to the Zusanli (ST36) and Sanyinjiao (SP6) points, but not to non-acupoints,
      produces a significant and long-lasting reduction of the mechanical hyperalgesia
      induced by the surgical incision of the plantar surface of the ipsilateral hind
      paw. The tension threshold was reduced from 75 to 27.6 +/- 4.2 g in animals soon
      after the end of electroacupuncture. The mechanical threshold in this group was
      about 64% less than in control. Electroacupuncture was ineffective in rats
      treated 10 min earlier with naloxone (1 mg/kg, ip), thus confirming the
      involvement of opioid mechanisms in the antinociceptive effects of such
      procedure. The results indicate that post-incisional pain is a useful model for
      studying the anti-hyperalgesic properties of electroacupuncture in laboratory
      animals.

PMID- 10920440
TI  - Further analysis of open-respirometry systems: an a-compartmental mechanistic
      approach.
AB  - A system is said to be "instantaneous" when for a given constant input an
      equilibrium output is obtained after a while. In the meantime, the output is
      changing from its initial value towards the equilibrium one. This is the
      transient period of the system and transients are important features of open
      respirometry systems. During transients, one cannot compute the input amplitude
      directly from the output. The existing models (e.g., first or second order
      dynamics) cannot account for many of the features observed in real open
      respirometry systems, such as time lag. Also, these models do not explain what
      should be expected when a system is speeded up or slowed down. The purpose of the
      present study was to develop a mechanistic approach to the dynamics of open
      respirometry systems, employing basic thermodynamic concepts. It is demonstrated
      that all the main relevant features of the output dynamics are due to and can be
      adequately explained by a distribution of apparent velocities within the set of
      molecules travelling along the system. The importance of the rate at which the
      molecules leave the sensor is explored for the first time. The study approaches
      the difference in calibrating a system with a continuous input and with a "unit
      impulse": the former truly reveals the dynamics of the system while the latter
      represents the first derivative (in time) of the former and, thus, cannot
      adequately be employed in the apparent time-constant determination. Also, we
      demonstrate why the apparent order of the output changes with volume or flow.

PMID- 10920439
TI  - Vasorelaxant effects of the potassium channel opener SR 47063 on the isolated
      human saphenous vein and rat aorta.
AB  - The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1, 2-dihydropyrid-1-yl)-2,2
      dimethyl-6-nitr ochromene), a new K(+)-channel opener structurally related to
      levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta
      (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and
      cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1
      nM to 1 microM) in the presence or absence of 3 microM glibenclamide. SR 47063
      potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10
      microM noradrenaline in a concentration-dependent manner, showing slightly
      greater activity in the aorta. The potency of the effect of SR 47063 on HSV and
      RA was 12- and 58-fold greater, respectively, than that reported for the
      structurally related K(+)-channel opener levcromakalim. The vasorelaxant action
      of SR 47063 in both blood vessels was strongly inhibited by 3 microM
      glibenclamide, consistent with a mechanism of action involving ATP-dependent K(+)
      channels.

PMID- 10920441
TI  - [Public health in the 20th century].

PMID- 10920442
TI  - Assessing the effects of global warming and local social and economic conditions
      on the malaria transmission.
AB  - OBJECTIVE: To show how a mathematical model can be used to describe and to
      understand the malaria transmission. METHODS: The effects on malaria transmission
      due to the impact of the global temperature changes and prevailing social and
      economic conditions in a community were assessed based on a previously presented
      compartmental model, which describes the overall transmission of malaria.
      RESULTS/CONCLUSIONS: The assessments were made from the scenarios produced by the
      model both in steady state and dynamic analyses. Depending on the risk level of
      malaria, the effects on malaria transmission can be predicted by the temperature
      ambient or local social and-economic conditions.

PMID- 10920443
TI  - Malaria transmission model for different levels of acquired immunity and
      temperature-dependent parameters (vector).
AB  - OBJECTIVE: Describe the overall transmission of malaria through a compartmental
      model, considering the human host and mosquito vector. METHODS: A mathematical
      model was developed based on the following parameters: human host immunity,
      assuming the existence of acquired immunity and immunological memory, which
      boosts the protective response upon reinfection; mosquito vector, taking into
      account that the average period of development from egg to adult mosquito and the
      extrinsic incubation period of parasites (transformation of infected but non
      infectious mosquitoes into infectious mosquitoes) are dependent on the ambient
      temperature. RESULTS: The steady state equilibrium values obtained with the model
      allowed the calculation of the basic reproduction ratio in terms of the model's
      parameters. CONCLUSIONS: The model allowed the calculation of the basic
      reproduction ratio, one of the most important epidemiological variables.

PMID- 10920444
TI  - [Identification of the encephalitis equine virus, Parana, Brazil].
AB  - INTRODUCTION: In the period of 1996-1999 some virus associated with encephalitis
      have been reported in horses from different regions of Parana State, Brazil. To
      identify the etiologic agent associated with this illness, mosquitoes and serum
      samples were collected in the endemic area. METHODS: The study area corresponded
      to four municipalities of Parana State, Brazil. Mosquitoes were captured in
      Shannon trap and human bait. After identification, they were processed for virus
      isolation. Blood of equines were collected in the municipalities of Querencia do
      Norte and Colorado. Antibodies to different Alphavirus and Flavivirus were
      analyzed by hemagglutination inhibition test. Specific seroneutralization
      reactions were performed in those sera with a positive reaction in the
      hemagglutination test. RESULTS: The mosquitoes genus collected were: Culex,
      Aedes, Mansonia, Coquillettidia, Psorophora, Sabethes, Wyeomyia, and Limatus.
      Even thought no virus was isolated, serologic analyses showed hemagglutinazing
      antibodies to Eastern equine encephalitis, Mucambo, Pixuna, Maguari, and St Luis
      encephalitis viruses. The neutralization test showed specific reaction to Eastern
      equine encephalitis virus in 12 tested sera. CONCLUSIONS: Species of mosquitoes
      that could be potential vectors of encephalitis, buniavirus, and other
      arboviruses of epidemiological importance were collected. It is believed that
      Eastern equine encephalitis virus affected the equines populations in the study
      regions because of the symptoms and antibodies for the virus in the sera detected
      in these equines.

PMID- 10920445
TI  - [Serological survey on arbovirus infection in residents of an ecological
      reserve].
AB  - OBJECTIVE: Serological inquires conducted in the Ribeira Valley, S. Paulo State,
      Brazil, showed an intense circulation of pathogenic arboviruses in the region.
      The goal was to verify the prevalence of arboviral infections in people living at
      the local ecological, and its potential association with these population'
      individual and familiar characteristics. METHODS: The study was carried out among
      182 persons of 58 families to identify the presence of antibodies to the
      following viruses: Rocio (ROC), Ilheus (ILH), Eastern equine encephalitis virus
      (EEE), Western equine encephalitis virus (WEE), Venezuelan equine encephalitis
      virus (VEE) and St. Louis encephalitis virus (SLE). Inhibition hemagglutination
      test and plaque reduction neutralization test were the laboratory assays of
      choice. MAC-ELISA was used to identify IgM antibodies to ROC, ILH and EEE
      viruses. RESULTS: The prevalence of antibodies was 26.9% (21. 4% to alphavirus
      and 12.6% to flavivirus). There were no antibodies to WEE virus. IgM antibodies
      were not observed suggesting no recent infection in study population. Among the
      characteristics investigated, age, occupation, place of birth and the habit of
      going into the forest were shown to be statistically associated with arboviral
      infection (p<0.05). CONCLUSIONS: It was observed an intense circulation of
      pathogenic arboviruses, especially VEE. It seems the habit of going into the
      forest is the most important factor to this population exposure to the mosquito
      vectors of arboviruses. The results suggest the need of further investigation to
      clarify the role of birds as arbovirus infection amplificators indoors.

PMID- 10920446
TI  - [Ecology of mosquitoes (Diptera: Culicidae) in areas of Serra da Bocaina National
      Park, Brazil. I. Habitat distribution].
AB  - OBJECTIVE: To assess the mosquito fauna in Serra da Bocaina National Park (PNSB),
      by collecting information through a general survey, and investigating the
      population behavior in habitats within the park with different vegetation.
      METHODS: Human bait collections were conducted once a month for both the forest
      and households, in diurnal and nocturnal periods, three time a day, throughout 24
      months, from January 1991 to December 1992. RESULTS: A total of 11, 808 adult
      mosquitoes belonging to 28 species were collected. Runchomyia reversa and
      Anopheles cruzii were the most abundant, reaching 52.5% and 17.9% of the total
      collected specimens, respectively. In the dense forest, Ru. reversa comprised
      59.4% of the total, followed by Ru. frontosa with 10.5%, and An. cruzii with
      9.9%. In the high altitude fields and in gallery forest, An. cruzii was the most
      abundant (48.1%) followed by Ru. reversa (28.1%). Inside households An. cruzii
      was also the most prominent species, representing 73.7% of the total for that
      location. Coquillettidia chrysonotum was the only species mainly seen in the
      household surroundings, where its distribution was: 14.9% (indoors), 19.4% (close
      to the house), and 65.7% (outdoors). An. cruzii and Ru. reversa were found
      throughout the whole year and captured every month. CONCLUSIONS: Mosquitoes in
      PNSB present an assynanthropic behavior, except for Cq. chrysonotum which lives
      preferentially in the household environment. Though An. cruzii is an
      assynantropic species it may approaches live near households and even invades and
      infest them for the blood meals. The occurrence of Aedes serratus in the
      household vicinity emphasizes its epidemiological importance as a potential
      vector of arboviruses. Sabethini are all exclusively sylvatic species.

PMID- 10920447
TI  - [Changes in composition and appropriate nutrition of family diet in the
      metropolitan areas of Brazil (1988-1996)].
AB  - OBJECTIVE: A new family budget survey carried out in the mid-nineties in Brazil
      allows an update of the secular trends (1962-1988) of dietary patterns of
      Brazilian population living in metropolitan areas. METHODS: Data sources are IBGE
      Institute of Statistics family budget surveys carried out from March 1987 to
      February 1988 (13,611 households) and from October 1995 to September 1996 (16,014
      households) in all metropolitan areas of Brazil. The daily food availability per
      capita for each household was calculated dividing the total food acquired in a
      month by the number of individuals living in a household and the month's number
      of days. Dietary patterns were characterized according to the amount of selected
      food groups and nutrients relative to the diet caloric input. Comparisons between
      the two surveys included the metropolitan area population as a whole and
      subgroups from less (North and Northeast) and more developed (Mid-west, Southeast
      and South) regions. RESULTS: It was observed an increase in consumption of meat
      and dairy products (except for butter) and a reduction in eggs consumption in
      both less and more developed regions. Beans, roots and tubers consumption showed
      a steady decline in the whole country while cereals consumption remained the same
      (higher in developed regions) or had a slight increase (in less developed
      regions). The proportional consumption of vegetal oils and margarine remained
      constant in the less developed regions but their consumption was greatly reduced
      in the more developed ones. CONCLUSIONS: An increase in the diet's lipid content
      in less developed regions and of saturated fat in the country as a whole,
      associated with a decrease or even no consumption of beans, vegetables, fruits
      and complex carbohydrates, and a further increase in the excessive sugar
      consumption are the negative aspects of the trend observed from 1988 to 1996.
      Changes that may indicate a growing awareness of the population toward a
      healthier diet, such as a decline in egg intake and a slight reduction in diets
      with a high total lipid content, were found only in more developed regions.

PMID- 10920448
TI  - [Maternal nutrition and duration of breastfeeding in a birth cohort in Pelotas,
      Brazil].
AB  - OBJECTIVE: The effects of maternal nutritional status on the duration of
      breastfeeding are inconsistent in the literature. A population-based cohort study
      was set to investigate this relationship. METHODS: Nine hundred and seventy seven
      mothers giving birth in 1993 (20% of that year's births) were studied. Studied
      maternal characteristics included nutritional status, social, economic, and
      demographic variables. The effects of these variables on the prevalence of
      breastfeeding at six months were analyzed through logistic regression. Cox
      regression was applied to analyze the effects on the duration of breastfeeding.
      RESULTS: Multivariate logistic regression analysis showed a higher prevalence of
      breastfeeding among women with a pre-pregnancy weight of 49 kg or more (odds
      ratio = 1.31; CI(95%) 1.04 - 1.64). The association with maternal height was not
      significant (p=0.06). Cox regression also showed a non-significant protective
      effect of having a higher pre-pregnancy weight (hazard ratio = 0.91; CI(95%) 0.82
      - 1.01). The duration of breastfeeding duration was not associated with maternal
      height. Weight gain during pregnancy was not associated with breastfeeding in
      either analyses. Other variables associated with the duration of breastfeeding in
      both analyses were maternal age, parity, smoking, and gestational age. Family
      income was associated with the prevalence of breastfeeding at six months, and
      birthweight was associated with the duration of breastfeeding. CONCLUSIONS: Pre
      pregnancy nutritional status is a stronger predictor of breastfeeding than weight
      gain during pregnancy.

PMID- 10920449
TI  - [Evaluation of mother-and-child health care in an urban area of Southern Brazil].
AB  - OBJECTIVE: To describe and analyze primary health care provided to mother-and
      child population in Teresopolis, state of Rio de Janeiro, Brazil. METHODS: A
      population survey was performed at the main vaccination station on the local
      Vaccine National Day, to collect information about the use of health care
      services and preventive primary care. RESULTS: Information was collected from 329
      mothers and their children. More than 90% of children had at least one pediatric
      visit in the past three months. Almost all had their growth chart, but in 30% of
      them the child's weight was not registered. There was a positive association
      between having a routine visit and the registration of the child's weight in the
      card (RP = 1.34; IC: 1.13-1.58; p = 0.0002). Around 59% of the mothers had a
      medical visit after giving after birth; 25% said they had never had a Pap smear
      test before, and 36% never had a breast examination. There was a positive
      association between the mother's age being over 20 years and ever having a Pap
      smear test (RP = 1.56; IC: 1.08-2.26; p = 0.03). Almost 70% of the mothers
      referred the use of any contraception method, and the most common used were
      contraceptive pills, condoms and tubal ligation. CONCLUSIONS: Despite some
      limitations, the results suggest a valid and useful methodology, which allows the
      identification of important needs in primary health care delivery to children and
      their mothers.

PMID- 10920450
TI  - [Hospital system as a source of information to estimate stillbirth and neonatal
      mortality rates].
AB  - OBJECTIVE: Studies on the evolution of infant mortality rate are very relevant.
      Nevertheless, lack of vital statistics in Brazil limits the temporal and spatial
      analysis of this indicator. This study aims to investigate the possible use of
      the Brazilian Hospital Information System as an alternative information source
      for stillbirth and neonatal mortality rates by age group. METHODS: A new method
      to estimate the stillbirth and neonatal mortality rates is proposed. It was
      applied in a set of selected Brazilian states in the year of 1995. For
      comparative purposes, the Brazilian Death Information System was assessed to
      estimate the mortality rates under study, after adjusting the registered number
      of live births by using a demographic tool. RESULTS: By assessing the Hospital
      Information System a larger number of fetal and early neonatal deaths were
      observed when compared to data given by the death information system of the
      Northeastern states. Besides, in the Southern and Southeastern states, where
      death records are more thorough, the mortality rates calculated using both
      information sources were very similar. CONCLUSIONS: The results suggest that the
      proposed methodology could greatly contribute to the analysis of the spatial-time
      evolution of stillbirth and neonatal death rates in recent years in Brazil, as
      data on death registration in the majority of the Brazilian states are less
      thorough than those from the hospital information system.

PMID- 10920451
TI  - Predicting the revolving door phenomenon among patients with schizophrenic,
      affective disorders and non-organic psychoses.
AB  - OBJECTIVE: The aim of the study was to identify the variables that predict the
      revolving door phenomenon in psychiatric hospital at the moment of a second
      admission. METHODS: The sample consisted of 3,093 patients who have been followed
      during 5 to 24 years after their first hospital admission due to schizophrenia,
      and affective or psychotic disorders. Those who had had four or more admissions
      during the study period were considered as revolving door patients. Logistic
      regression analyses were used to assess the impact of gender, age, marital
      status, urban conditions, diagnosis, mean period of stay on the first admission,
      interval between the first and second admissions on the patterns of
      hospitalization. RESULTS: The variables with the highest predictive power for
      readmission were the interval between first and second admissions, and the length
      of stay in the first admission. CONCLUSIONS: These data may help public health
      planners in providing optimal care to a small group of patients with more
      effective utilization of the available services.

PMID- 10920452
TI  - [Serological markers of hepatitis B in people submitted to blood testing in
      health care clinics].
AB  - OBJECTIVE: To study some of the epidemiological aspects of hepatitis B in a non
      representative sample of patients seen in health care clinics. METHODS: The study
      population comprised 632 patients who were seen at health care clinics in the
      city of Ribeirao Preto, Brazil, for the purpose of blood testing, regardless the
      reason. After signing a written consent, an additional amount of blood was drawn
      from the same venous puncture site used to collect the original sample for the
      testing assigned to the patient at the health care clinic. A questionnaire was
      applied to each participant, looking for the presence of risk factors for
      hepatitis B. The blood samples were tested for HBV markers, using immunoenzimatic
      techniques. RESULTS: The prevalences of HBsAg and anti-HBcAg were 0.3% and 13.9%,
      respectively. By a logistic regression model, the following variables were
      significantly associated with the infection: age, time of residency in the city
      (higher risk among those living for a period less than one year), past history of
      hepatitis, incarceration and sexual behavior (higher risk among homosexual and
      bisexual males). CONCLUSIONS: The growing difficulties in obtaining blood samples
      from a representative group of patients, as done in classic surveys, make it
      necessary to look for alternative methodologies which can provide information
      concerning the presence of infectious agents in a community. Though the results
      cannot be generalized to the population as a whole, the methodology used conveyed
      some knowledge regarding the circulation of hepatitis B virus. In addition, it
      makes much easier to obtain agreement from the participants, since it does not
      add any invasive procedure. Despite the limitations, this methodology may be
      helpful in epidemiological surveillance of infectious agents known as producing
      asymptomatic infections in much of the population.

PMID- 10920453
TI  - [Profile of occupational disease outpatients and the presence of repetitive
      strain injury].
AB  - OBJECTIVE: To assess the profile of outpatients seen at an occupational disease
      clinic of a general and repetitive strain injury (RSI) patients by using
      multivariate analyze. METHODS: The first 565 visit registries for the year 1996
      were assessed regarding their social and demographics aspects, work
      characteristics, and diagnosis. All the variables were analyzed by univariate
      analysis method. Bivariate data were analyzed using Chi square test (chi2) for
      categorical variables, comparison of means or ranges for quantitative and
      categorical variables. Multivariate data were analyzed using log-linear models
      with logit-transformation to identify the groups with a larger proportion of RSI.
      RESULTS: Women sought the occupational diseases clinic more frequently than men,
      and there was a predominance of RSI cases. The occupation distribution was in
      order of priority as following: office workers, factory workers, and service
      workers. Of them, 56.9% were from the economic sector of services. RSI was seen
      in 56% of the patients diagnosed at their first visit. CONCLUSIONS: The analysis
      confirms the trends seen in the 80s regarding the epidemiological changes in
      occupational diseases, when RSI started to be identified and displaced to a
      secondary position the other common diseases (due to physical and chemical
      hazards) because of inadequacy of ergonomics.

PMID- 10920454
TI  - [The relationship between oral habits and malocclusion in preschool children].
AB  - OBJECTIVE: To evaluate the way oral habits and speech problems affect dental
      occlusion in preschool children. METHODS: A random sample of 2,139 boys and girls
      aged 3-5 years old was evaluated. The children were enrolled in private and state
      institutions in the city of Bauru, Sao Paulo State, Brazil. The cross-sectional
      study was developed in two steps: occlusion assessment, and a questionnaire about
      their social and economic status. The occlusal anatomical-functional
      characteristics assessment was done according to Angle classification.
      Additionally, overjet, overbite, crowding, anterior open bite, posterior
      crossbite, and anterior crossbite were evaluated. A sub-sample of 618 children
      filled out the questionnaire. The prevalence of malocclusion and some variables
      of exposure were tested by bivariate analysis. RESULTS: The prevalence of
      malocclusion was 51.3% for boys and 56.9% for girls. There was no difference
      related to gender. In regard to age, there was a higher prevalence of
      malocclusion in the 3 year-old group, which decreased significantly with age
      (p<0.05). CONCLUSIONS: Among the environmental factors evaluated, the habit of
      sucking a pacifier was the most important in the association with malocclusion
      (OR=5.46) followed by the habit of sucking fingers (OR=1.54). Speech problems did
      not show any influence in malocclusion occurrence.

PMID- 10920455
TI  - [Dental caries prevalence and mean dmf-t among 12 to 13-years old schoolchildren
      between 1971 and 1997, Southern Brazil].
AB  - INTRODUCTION: Cross-sectional surveys carried out in Brazil during the last
      decade have showed a significant decrease in both prevalence and severity of
      dental caries. However, the validity of these studies is questioned. Different
      methodologies as well as diagnosis criteria were used. Thus, a study was carried
      out with the purpose of comparing the prevalence and severity of caries among
      schoolchildren aged 12 and 13 years in a region of Brazil. METHODS: Two cross
      sectional surveys were carried out. All 12 and 13 year old children enrolled in a
      primary school were examined by a single dentist in 1971 (n=202) and 1997
      (n=175), following the same protocol. The original criteria for the diagnosis of
      caries proposed by Klein and Palmer in 1937 were used both in 1971 and 1997. A
      total of 202 and 175 children were examined in 1971 and 1997 respectively.
      RESULTS: The response rate was 100%. Intra-examiner agreement was very high.
      Kappa test was performed on a tooth by tooth basis and all values were above
      0.86. The prevalence of caries was 98% and 93. 7% in 1971 and 1997 respectively.
      Comparison of the severity of caries experience expressed as changes in the mean
      DMF-T scores showed a reduction from 9.2 to 6.2 between 1971 and 1997 in the
      study group. CONCLUSIONS: There was a significant reduction in dental caries
      prevalence and severity between 1971 to 1997 in the study population. The
      observed reduction of caries was not a statistical artifact as the same
      methodology and diagnostic criteria were applied in both cross-sectional surveys.

PMID- 10920456
TI  - [Pesticide impact on health: a study of tomato cultivation].
AB  - OBJECTIVE: In addition to water contamination, the presence of pesticide residues
      in food poses a risk to the population, being a serious public health problem in
      Brazil. With the purpose of getting a better understanding of this scenario, the
      use of pesticides in tomato crops in the State of Pernambuco, Brazil, was
      studied. METHODS: Questionnaires were applied to obtain social and environmental
      information as well as morbidity rates and additional data on rural workers
      involved in tomato plantations in two regions of Pernambuco, Brazil.
      RESULTS/CONCLUSIONS: The results obtained in the two studied regions show that
      there is a lack effective policies to both protect the health of rural workers
      who have to deal with pesticides and the environment which has already been
      severely damaged.

PMID- 10920458
TI  - [ [In Process Citation]

PMID- 10920457
TI  - [First report of Aedes albopictus in areas of Mata Atlantica, Recife, PE,
      Brazil].
AB  - This is the first report of the presence of Aedes albopictus in the native rain
      forest, near the urban area of Recife (State of Pernambuco, Brazil). Adult female
      mosquitoes were collected using human bait. Mosquitoes in aquatic stages were
      looked for in treeholes, bamboos, bromeliads and old tires. The existence of Ae.
      albopictus in the metropolitan area of Recife poses a potential risk for the
      interaction of this mosquito species with the urban human population.

PMID- 10920459
TI  - A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal
      cortical binding in major depression and suicide.
AB  - BACKGROUND: Major depression and suicide are associated with fewer serotonin
      transporter (5-HTT) sites. The 5'-flanking promoter region of the 5-HTT gene has
      a biallelic insertion/deletion (5-HTTLPR). We assayed prefrontal cortical (PFC) 5
      HTT binding in major depression and suicide and examine the relationship to the 5
      HTTLPR allele. METHODS: Postmortem brain samples from 220 individuals were
      genotyped for the 5-HTTLPR polymorphism. Binding of 5-HTT was assayed by
      quantitative autoradiography in the PFC of a subset of subjects (n = 159).
      Clinical information, including DSM-III-R Axis I diagnoses, was obtained by
      psychological autopsy and medical chart review. RESULTS: Binding to 5-HTT was
      lower in the ventral PFC of suicides compared with nonsuicides and was lower
      throughout the PFC of subjects with a history of major depression. The 5-HTTLPR
      genotype was associated with major depression but not with suicide or 5-HTT
      binding. CONCLUSIONS: A diffuse reduction of 5-HTT binding in the PFC of
      individuals with major depression may reflect a widespread impairment of
      serotonergic function consistent with the range of psychopathologic features in
      major depression. The localized reduction in 5-HTT binding in the ventral PFC of
      suicides may reflect reduced serotonin input to that brain region, underlying the
      predisposition to act on suicidal thoughts. The 5-HTTLPR genotype was not related
      to the level of 5-HTT binding and does not explain why 5-HTT binding is lower in
      major depression or suicide. Arch Gen Psychiatry. 2000;57:729-738

PMID- 10920460
TI  - Searching for the chicken's egg in transporter gene polymorphisms.

PMID- 10920461
TI  - A functional neuroanatomy of tics in Tourette syndrome.
AB  - BACKGROUND: Tics are involuntary, brief, stereotyped motor and vocal behaviors
      often associated with irresistible urges. They are a defining symptom of the
      classic neuropsychiatric disorder, Tourette syndrome (TS), and constitute an
      example of disordered human volition. The neural correlates of tics are not well
      understood and have not been imaged selectively. METHODS: Event-related
      [(15)O]H(2)O positron emission tomography techniques combined with time
      synchronized audio and videotaping were used to determine the duration of,
      frequency of, and radiotracer input during tics in each of 72 scans from 6
      patients with TS. This permitted a voxel-by-voxel correlational analysis within
      Statistical Parametric Mapping of patterns of neural activity associated with the
      tics. RESULTS: Brain regions in which activity was significantly correlated with
      tic occurrence in the group included medial and lateral premotor cortices,
      anterior cingulate cortex, dorsolateral-rostral prefrontal cortex, inferior
      parietal cortex, putamen, and caudate, as well as primary motor cortex, the
      Broca's area, superior temporal gyrus, insula, and claustrum. In an individual
      patient with prominent coprolalia, such vocal tics were associated with activity
      in prerolandic and postrolandic language regions, insula, caudate, thalamus, and
      cerebellum, while activity in sensorimotor cortex was noted with motor tics.
      CONCLUSIONS: Aberrant activity in the interrelated sensorimotor, language,
      executive, and paralimbic circuits identified in this study may account for the
      initiation and execution of diverse motor and vocal behaviors that characterize
      tics in TS, as well as for the urges that often accompany them. Arch Gen
      Psychiatry. 2000;57:741-748

PMID- 10920462
TI  - A mind that tics.

PMID- 10920463
TI  - 24-Hour monitoring of cortisol and corticotropin secretion in psychotic and
      nonpsychotic major depression.
AB  - BACKGROUND: Considerable research has been devoted to the hypothalamic-pituitary
      adrenal (HPA) axis in depression, but relatively little attention has been given
      to intensive monitoring of hormone secretion over time. Such research is
      potentially important because the HPA axis has prominent circadian and ultradian
      periodicity. Comparison of depressed patients with and without psychotic features
      is also important because HPA axis abnormalities may be especially pronounced in
      psychotic depressed patients. METHODS: Eleven patients with psychotic major
      depression (PMD patients), 38 patients with nonpsychotic major depression (NPMD
      patients), and 33 healthy control subjects, all drug free, were studied. Patients
      with PMD and NPMD were outpatients recruited primarily by advertisement. Subjects
      were admitted to a General Clinical Research Center and had blood drawn through
      an intravenous line for determination of cortisol and corticotropin (ACTH) levels
      every hour for 24 hours. RESULTS: Among NPMD patients, the 24-hour cortisol
      amplitude was significantly (P =.02) reduced in comparison with control subjects,
      while ACTH indices did not differ between NPMD patients and the control group.
      Among PMD patients, the ACTH 24-hour mean was significantly (P =.03) increased
      compared with controls, while PMD patients and the control group did not differ
      significantly in cortisol indices. CONCLUSION: In the population studied, PMD and
      NPMD patients have distinct profiles of HPA axis dysregulation.

PMID- 10920464
TI  - Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia.
AB  - BACKGROUND: Converging neuroanatomic, neurophysiological, and neurobehavioral
      evidence implicate prefrontal subregions in schizophrenia. Neuroanatomic studies
      with magnetic resonance (MR) imaging enable regional volume parcellation.
      Inconsistent reports may relate to variable methods and small samples. We
      attempted to resolve volume differences within sectors of the prefrontal lobe in
      a large sample, relating volumes to clinical and neurocognitive features.
      METHODS: Magnetic resonance imaging was performed in 70 patients with
      schizophrenia (40 men and 30 women; 29 neuroleptic naive and 41 previously
      treated) and 81 healthy controls (34 men and 47 women). Gray and white matter
      volumes of the dorsolateral, dorsomedial, orbitolateral, and orbitomedial
      prefrontal cortex were quantified. Symptoms, functioning, and neurocognition were
      assessed concurrently. RESULTS: Reduced prefrontal gray matter volume was
      observed in patients. The reduction was evident for the dorsolateral area in men
      (9%) and women (11%), for the dorsomedial area only in men (9%), and for orbital
      regions only in women (23% and 10% for lateral and medial, respectively). The
      reduction of orbital volume in women was associated with poorer premorbid
      functioning, more severe negative symptoms, and depression. Volume of dorsal
      cortex was positively associated with better performance on abstraction and
      attention tasks across all groups. CONCLUSIONS: Schizophrenia is associated with
      reduced gray matter volume in prefrontal cortex, which affects men and women in
      the dorsolateral sector. The effects are moderated by sex for dorsomedial and
      orbital regions and are related to symptom severity and cognitive function. This
      is not a by-product of treatment, since the differences are evident in
      neuroleptic-naive patients.

PMID- 10920465
TI  - Temporolimbic volume reductions in schizophrenia.
AB  - BACKGROUND: Neuroanatomic studies of schizophrenia have reported temporolimbic
      abnormalities. Most magnetic resonance imaging studies have evaluated small
      samples of primarily men with chronic schizophrenia. Our goal was to evaluate sex
      differences in segmented temporal lobe subregions with reliable parcellation
      methods, relating volume with clinical and neurocognitive parameters. METHODS:
      Magnetic resonance imaging was performed in 100 patients with schizophrenia (58
      men, 42 women; 39 neuroleptic naive, 61 previously treated) and 110 healthy
      controls (51 men, 59 women). Gray and white matter volumes of temporolimbic
      (hippocampus and amygdala) and neocortical regions (superior temporal gyrus and
      temporal pole) were examined. Symptoms, functioning, and neurocognition were
      assessed concurrently. RESULTS: Hippocampal gray matter volume was reduced in men
      (7%) and women (8.5%) with schizophrenia. In the amygdala, however, decreased
      volume was evident for men (8%) whereas women (10.5%) had increased volume.
      Magnetic resonance imaging of the temporal pole showed decreased gray matter in
      men (10%) and women (8.5%). For the superior temporal gyrus, the decrease
      exceeded that of whole-brain only in men (11.5%). Volumes were largely
      uncorrelated with clinical measures, but higher hippocampal volumes were
      associated with better memory performance for all groups. Cortical volumes were
      associated with better memory performance in healthy women. CONCLUSIONS:
      Schizophrenia is associated with reduced gray matter volume in temporolimbic
      structures. In men, reduction was manifested in all regions, whereas women showed
      decreased hippocampal volumes but increased amygdala volumes. The abnormalities
      are evident in patients with first-episode schizophrenia and correlate more
      strongly with cognitive performance than with symptom severity.

PMID- 10920466
TI  - Psychological responses of women after first-trimester abortion.
AB  - BACKGROUND: Controversy exists over psychological risks associated with abortion.
      The objectives of this study were to examine women's emotions, evaluations, and
      mental health after an abortion, as well as changes over time in these responses
      and their predictors. METHODS: Women arriving at 1 of 3 sites for an abortion of
      a first-trimester unintended pregnancy were randomly approached to participate in
      a longitudinal study with 4 assessments-1 hour before the abortion, and 1 hour, 1
      month, and 2 years after the abortion. Eight hundred eighty-two (85%) of 1043
      eligible women approached agreed; 442 (50%) of 882 were followed for 2 years.
      Preabortion and postabortion depression and self-esteem, postabortion emotions,
      decision satisfaction, perceived harm and benefit, and posttraumatic stress
      disorder were assessed. Demographic variables and prior mental health were
      examined as predictors of postabortion psychological responses. RESULTS: Two
      years postabortion, 301 (72%) of 418 women were satisfied with their decision;
      306 (69%) of 441 said they would have the abortion again; 315 (72%) of 440
      reported more benefit than harm from their abortion; and 308 (80%) of 386 were
      not depressed. Six (1%) of 442 reported posttraumatic stress disorder. Depression
      decreased and self-esteem increased from preabortion to postabortion, but
      negative emotions increased and decision satisfaction decreased over time.
      Prepregnancy history of depression was a risk factor for depression, lower self
      esteem, and more negative abortion-specific outcomes 2 years postabortion.
      Younger age and having more children preabortion also predicted more negative
      abortion evaluations. CONCLUSIONS: Most women do not experience psychological
      problems or regret their abortion 2 years postabortion, but some do. Those who do
      tend to be women with a prior history of depression.

PMID- 10920467
TI  - Abortion and the null hypothesis.

PMID- 10920468
TI  - Reduced brain norepinephrine and dopamine release in treatment-refractory
      depressive illness: evidence in support of the catecholamine hypothesis of mood
      disorders.
AB  - BACKGROUND: The etiology of depressive illness has been linked with brain
      monoaminergic neuronal dysfunction, yet the development of sensitive markers of
      endogenous depression has proven difficult. METHODS: Using catheters placed in an
      internal jugular vein, we estimated the release of brain monoamine
      neurotransmitters in 19 healthy volunteers and in 9 patients with nonbipolar
      depressive illness refractory to medication at rest and following intravenous
      desipramine hydrochloride. Venoarterial plasma concentration gradients were used
      to quantify the amount of neurotransmitters stemming from the brain. Cerebral
      oxidative metabolism was assessed concurrently from measurements of oxygen and
      carbon dioxide gas exchange via the process of regional indirect calorimetry.
      RESULTS: The brains of these patients exhibited reduced venoarterial
      norepinephrine (4.0 +/- 2.7 nmol/L vs 0.7 +/- 1.3 nmol/L) and homovanillic acid
      concentration gradients (8.3 +/- 7.8 nmol/L vs 3.1 +/- 1.9 nmol/L), and used an
      energy source other than glucose. Internal jugular 5-hydroxyindoleacetic acid
      concentration gradients were not reduced in the patients with depressive illness.
      While both the reduction in norepinephrine turnover and the defect in cerebral
      metabolism were normalized following pharmacological blockade of the
      norepinephrine transporter with desipramine, paradoxically it was the brain's
      turnover of dopamine that bore a significant relation to the patients' clinical
      status (r(s) = 0.79, P =.02). The positive nature of this relationship remains
      difficult to reconcile. CONCLUSIONS: In accordance with the monoamine hypothesis,
      a deficit in brain norepinephrine and dopamine exists in patients with depressive
      illness. Moreover, the brains of these patients use an energy source other than
      glucose, a situation that is normalized following the acute pharmacological
      blockade of the norepinephrine transporter with the tricyclic antidepressant,
      desipramine.

PMID- 10920469
TI  - A double-blind, placebo-controlled study of risperidone addition in serotonin
      reuptake inhibitor-refractory obsessive-compulsive disorder.
AB  - BACKGROUND: To date, only 1 controlled study has found a drug (haloperidol) to be
      efficacious in augmenting response in patients with obsessive-compulsive disorder
      (OCD) refractory to serotonin reuptake inhibitor (SRI) monotherapy; patients with
      comorbid chronic tic disorders showed a preferential response. This report
      describes the first controlled study of risperidone addition in patients with OCD
      refractory to treatment with SRI alone. METHODS: Seventy adult patients with a
      primary DSM-IV diagnosis of OCD received 12 weeks of treatment with an SRI.
      Thirty-six patients were refractory to the SRI and were randomized in a double
      blind manner to 6 weeks of risperidone (n = 20) or placebo (n = 16) addition.
      Behavioral ratings, including the Yale-Brown Obsessive Compulsive Scale, were
      obtained at baseline and throughout the trial. Placebo-treated patients
      subsequently received an identical open-label trial of risperidone addition.
      RESULTS: For study completers, 9 (50%) of 18 risperidone-treated patients were
      responders (mean daily dose, 2.2 +/-0.7 mg/d) compared with 0 of 15 in the
      placebo addition group (P<. 005). Seven (50%) of 14 patients who received open
      label risperidone addition responded. Risperidone addition was superior to
      placebo in reducing OCD (P<.001), depressive (P<.001), and anxiety (P =.003)
      symptoms. There was no difference in response between OCD patients with and
      without comorbid diagnoses of chronic tic disorder or schizotypal personalty
      disorder. Other than mild, transient sedation, risperidone was well tolerated.
      CONCLUSION: These results suggest that OCD patients with and without comorbid
      chronic tic disorders or schizotypal personality disorder may respond to the
      addition of low-dose risperidone to ongoing SRI therapy.

PMID- 10920470
TI  - Sex-specific genetic influences on the comorbidity of alcoholism and major
      depression in a population-based sample of US twins.
AB  - BACKGROUND: Alcoholism and depression frequently co-occur, but the origins of
      this comorbidity remain uncertain. Most previous family, twin, and adoption
      studies of these disorders have used cases ascertained through treatment
      settings, who may differ from cases in epidemiological samples. We studied the
      importance of genetic influences on risk for lifetime comorbidity of major
      depression and alcoholism by means of a population-based twin sample. METHODS:
      Lifetime major depression (MD), alcohol abuse, and alcohol dependence were
      assessed by structured interview for both members of 3755 twin pairs from the Mid
      Atlantic Twin Registry. Pair resemblance was analyzed by means of structural
      equation models. RESULTS: Individuals with MD were at significantly increased
      risk for alcohol dependence and for a combined diagnosis of alcohol abuse and/or
      dependence. History of MD in a twin significantly increased the risk of cotwin
      alcohol dependence and alcohol abuse and/or dependence among identical male pairs
      and for alcohol abuse and/or dependence in identical female pairs, but not among
      male or female fraternal pairs. Results of structural modeling indicate that
      comorbidity occurs because the genetic and specific environmental sources of
      liability to MD overlap with those underlying alcohol dependence and alcohol
      abuse and/or dependence. This overlap was significant only within sex, not across
      sexes. CONCLUSIONS: In this population-based twin sample, the familial
      transmission of MD and alcohol dependence was largely disorder specific.
      Comorbidity appears to be due to sex-specific genetic and environmental risk
      factors. The factors underlying depression in women do not appear to arise from
      the same factors underlying alcoholism in men.

PMID- 10920471
TI  - Fluvoxamine strongly inhibits melatonin metabolism in a patient with low
      amplitude melatonin profile.

PMID- 10920472
TI  - School predictors of schizophrenia.

PMID- 10920473
TI  - Bovine respiratory syncytial virus (BRSV): a review.
AB  - Bovine respiratory syncytial virus (BRSV) infection is the major cause of
      respiratory disease in calves during the first year of life. The study of the
      virus has been difficult because of its lability and very poor growth in cell
      culture. However, during the last decade, the introduction of new immunological
      and biotechnological techniques has facilitated a more extensive study of BRSV as
      illustrated by the increasing number of papers published. Despite this growing
      focus, many aspects of the pathogenesis, epidemiology, immunology etc. remain
      obscure. The course and outcome of the infection is very complex and
      unpredictable which makes the diagnosis and subsequent therapy very difficult.
      BRSV is closely related to human respiratory syncytial virus (HRSV) which is an
      important cause of respiratory disease in young children. In contrast to BRSV,
      the recent knowledge of HRSV is regularly extensively reviewed in several books
      and journals. The present paper contains an updated review on BRSV covering most
      aspects of the structure, molecular biology, pathogenesis, pathology, clinical
      features, epidemiology, diagnosis and immunology based on approximately 140
      references from international research journals.

PMID- 10920474
TI  - Functional anatomy of the omasum in high Arctic Svalbard reindeer (Rangifer
      tarandus platyrhynchus) and Norwegian reindeer (Rangifer tarandus tarandus).
AB  - The structure and fill of the omasum was investigated in summer and in winter in
      adult female reindeer living on the polar desert and tundra of the high Arctic
      archipelago of Svalbard and in sub-Arctic mountain habitats in northern Norway.
      The mean total mass of the omasum in non-lactating adult female Svalbard reindeer
      was 467 g (0.65 g per 100 g live body mass (BM)) in September and 477 g (1.03 g
      per 100 g BM) in April. By contrast, the mean mass of the omasum in non-lactating
      adult reindeer in northern Norway was 534 g (0.83 g per 100 g BM) in September
      but only 205 g (0.35 g per 100 g BM p < 0.05) in late March, owing to a decrease
      in both tissue mass and the wet mass of the contents of the organ. The mean
      absorptive surface of the omasum in Svalbard reindeer was 2300 cm2 in September
      and 2023 cm2 in April. In Norwegian reindeer, by contrast, the absorptive surface
      area decreased from 2201 cm2 in September to 1181 cm2 (p < 0.05) in late March.
      The marked seasonal decline of omasal tissue and contents in Norwegian reindeer
      probably results from intake of highly digestible forage plants, including
      lichens, in winter. Svalbard reindeer, a non-migratory sub-species, survive
      eating poor quality fibrous vascular plants in winter. The absence of any marked
      seasonal change in the mass, total absorptive surface area or filling of the
      omasum in Svalbard reindeer in winter despite a substantial decline in body mass
      presumably reflects their need to maintain maximum absorption of nutrients,
      including volatile fatty acids, when feeding on such poorly fermentable forage.

PMID- 10920475
TI  - Eradication of porcine sarcoptic mange within a health declared production model.
AB  - The success of a large-scale eradication programme against sarcoptic mange was
      evaluated in piglet producing herds belonging to the health class LSO 2000. These
      farms are monitored to be free from sarcoptic mange, swine enzootic pneumoniae,
      swine dysentery and progressive atrophic rhinitis. The local veterinarians were
      instructed to eradicate sarcoptic mange from the herds by 2 ivermectin injections
      14 days apart or 3 treatments with phoxim pour-on 6 days apart before the farms
      were able to join the health class. The study consisted of a questionnaire
      administered to the farmers, farm visits and follow-ups associated with the
      regular control of the health class. A questionnaire was sent to all of the 379
      accepted farrowing farms. Altogether 323 farmers had initiated an eradication
      programme at least 7 months before the questionnaire was distributed and 96% of
      them believed that the mange eradication programme had been successful. In most
      of the successful herds (90%), the local veterinarian had treated the animals by
      the recommended methods, and the majority of the farmers (88%) had cleaned and
      sprayed the pens with insecticides on the days of treatment. Three out of the 7
      unsuccessful farms had employed methods other than those recommended. Twenty-five
      herds were randomly selected for an intensified control. The rubbing index was <
      or = 0.1 in all herds visited, indicating freedom from mange. Sows or gilts, 15
      20 animals per farm, were skin scraped and no Sarcoptes scabiei was found. The
      same animals were blood sampled and serum antibodies to S. scabiei were measured
      by an indirect ELISA. All except 1 farm had low optical density (OD) values in
      most of the samples. The owner of that farm had become uncertain about the mange
      status of the herd and had recently retreated all animals with acaricides. The
      number of complaints about mange in the finishing units buying health class
      feeder pigs was low. The study demonstrates that it is possible to run an
      eradication programme against sarcoptic mange, in which a large number of farmers
      together with their veterinarians participate. It is possible to eradicate mange
      not only at the herd but also at the population level. The ELISA test employed
      proved to be a possible tool to monitor the efficacy of mange-eradication
      programmes.

PMID- 10920476
TI  - Sclerosis of the third carpal bone. A prospective study of its significance in a
      group of young standardbred trotters.
AB  - To assess the significance of radiographic signs of sclerosis of the third carpal
      bone (C3) in young Standardbred trotters in relation to performance, lameness and
      bone turnover both carpi in 14 Standardbred trotters were radiographically and
      scintigraphically examined 6 times, from the beginning of speed training until
      the beginning of racing, between the mean ages of 20 and 42 months. At the end of
      the study 8 horses had raced in official qualifying races and 14 limbs in 11
      horses had been diagnosed with carpal lameness. All horses but 2 developed
      sclerosis and all but one had increased bone turnover in the C3 area by
      scintigraphy. C3 sclerosis increased continuously over time and with increased
      performance. Carpal lameness was significantly associated with progression of
      sclerosis but in most cases sclerosis developed without concomitant signs of
      carpal lameness. No association between carpal lameness and increased
      scintigraphic uptake was found, but horses that had qualified for racing had
      significantly higher C3 to carpus ratio of radiopharmaceutical uptake. We
      conclude that there is a continuous increase in C3 radiographic sclerosis with
      time in young Standardbred trotters in professional training, but radiographic
      sclerosis appears to be of limited value as an indicator of clinical carpal
      disease or level of performance in Standardbred trotters.

PMID- 10920477
TI  - Factors prior to dry period associated with high and low levels of cow milk
      somatic cell counts in next lactation.
AB  - Data from a randomized controlled field study of selective dry cow therapy were
      used in which 686 cows had been allocated to 2 control groups (sampling only or
      placebo) or 2 therapy groups. Possible factors from previous lactation were
      assessed in determining their association with the probability of 'failure',
      designated as a cow milk somatic cell count (CMSCC) of greater than 399,000 per
      ml in geometric mean of several measurements during subsequent lactation. Success
      cows were those with a CMSCC of less than 200,000 per ml. For our analyses, this
      targeted 187 success cows and 186 failure cows. Therapy was given as a total dose
      of 400,000 IU penicillin and 100 mg neomycin per infected quarter as dry cow
      preparation once, or as a lactation formula with a total dose of 1.2 million IU
      penicillin and 1,200 mg dihydrostreptomycin per infected quarter during a 1-week
      period. Significant factors in the predictive model for success included therapy,
      low level of CMSCC (geometric mean of the 3 last tests) in previous lactation,
      low level of CMSCC (weighted by daily milk yield mean) in the herd, young cows,
      and not having had a case of treatment for chronic clinical mastitis. Additional
      information on the probability of failure in treated and untreated cows can be
      predicted by number of quarters infected with Staphylococcus aureus approximately
      1.5 months before drying off. The models derived are considered for use as tools
      in selective treatment and culling decisions.

PMID- 10920478
TI  - Age-dependent occurrence of the intestinal ciliate Balantidium coli in pigs at a
      Danish research farm.
AB  - A cross sectional study of the prevalence and intensity of Balantidium coli in
      pigs was carried out on a Danish research farm. The prevalence of B. coli
      infection increased from 57% in suckling piglets to 100% in most pig groups > or
      = 4 weeks old. The mean number of cysts per gram faeces (CPG) of pigs aged 12
      weeks and younger were < or = 206, whereas pigs aged 28 weeks and > 52 weeks had
      significantly higher counts of > or = 865 CPG. Although some lactating sows had
      very high CPG's, no significant differences in CPG could be detected between the
      intensities of pregnant sows, lactating sows and empty and dry sows. No human
      cases of B. coli infection have been published in Denmark though it is zoonotic.

PMID- 10920479
TI  - Redescription of Parafilaria bovicola Tubangui, 1934 (Nematoda: Filarioidea) from
      Swedish cattle.
AB  - Parafilaria bovicola was introduced into Sweden and identified for the first time
      in Swedish cattle in 1978. Since then the parasite has become well established
      and has been responsible for substantial economic losses in Swedish beef
      production. Although studies have been undertaken on serodiagnosis, life cycle,
      vector and geographical distribution within Sweden this is the first full
      description of P. bovicola from Swedish cattle and the first study to use
      scanning electron microscopy. P. bulgarica Daskalov, 1944 is regarded as a
      synonym of P. bovicola Tubangui, 1934. Tooth-like thickenings described on the
      anterior lobes of the oesophagus for the first time may assist the parasite in
      its migration through the host tissues.

PMID- 10920480
TI  - Lack of virus transmission from bovine viral diarrhoea virus infected calves to
      susceptible peers.
AB  - None of 14 calves not previously exposed to BVDV became infected after being
      forced to have nose-to-nose contact with a group of 5 calves primarily infected
      with BVDV. These were 5 male calves primarily infected with a type I BVDV strain,
      after nose-to-nose contact with a persistently viraemic calf. All 5 became
      infected and were clinically affected. They were slightly depressed and pyretic
      at 8-9 days post-infection, with a body temperature of up to 41.6 degrees C, but
      no medical treatment was required. Seroconversions to BVDV were detected in these
      calves at 14 to 21 days post-infection. The 14 healthy calves, proved to be free
      from BVD virus--as well as antibodies, were introduced 2 by 2 into the group of 5
      primarily infected calves on days 4, 7, 14, 21, 28, 35 and 42 after the 5 calves
      had been in contact with the persistently BVDV-infected calf. Each pair of calves
      stayed within the primarily infected group for 2 days. None of these 14 calves
      seroconverted to BVDV.

PMID- 10920481
TI  - Leishmaniosis mimicking oral neoplasm in a dog: an unusual manifestation of an
      unusual disease in Finland.

PMID- 10920482
TI  - [Nitrous oxide free low-flow anesthesia].
AB  - The routine use of nitrous oxide as a component of the carrier gas has been
      unanimously called into question in recent surveys, in fact, its use is now
      recommended in indicated cases only. Whereas a lot of contraindications are
      listed in the surveys, precise definitions of justified indications are not
      given. In clinical routine practice, there are absolutely no problems in carrying
      out inhalational anaesthesia without nitrous oxide. The missing analgetic effect
      can be compensated for by moderately increasing the additively used amount of
      opioids, while the missing hypnotic effect can be achieved by raising the expired
      concentration of the inhalational anaesthetic by not more than 0.2-0.25 x MAC.
      Thus, when isoflurane is used, an expired concentration of 1.2 vol% is desired,
      in the case of sevoflurane of 2.2 vol% and with desflurane of 5.0 vol%. In
      addition, doing without nitrous oxide facilitates the performance of low flow
      anaesthetic techniques considerably. Since the patient only inhales oxygen and
      the volatile anaesthetic, the total gas uptake is reduced significantly. Washing
      out nitrogen is no longer necessary. This means that the initial phase of low
      flow anaesthesia, during which high fresh gas flows have to be used, can be kept
      short. Its duration is now determined by the wash-in of the volatile anaesthetic.
      Since there is no uptake of nitrous oxide, a considerably greater volume of gas
      is circulating within the breathing system, minimizing the possibility of
      accidental gas volume deficiency. Thus, if anaesthesia machines with highly gas
      tight breathing systems are used, even the performance of non-quantitative closed
      system anaesthesia becomes possible in routine clinical practice. The carrier gas
      flow can be reduced to just that amount of oxygen which is really taken up by the
      patient. This oxygen volume can be roughly calculated by applying the Brody's
      formula. Using fresh gas flows as low as 0.25 l/min, however, will result in a
      significant decrease of the output of conventional vaporizers outside the
      circuit. Thus, it becomes nearly impossible to maintain an expired isoflurane
      concentration of 1.2 vol%. With respect to their pharmcokinetic properties, the
      newer low soluble volatile agents sevoflurane and desflurane are better suited
      for use with flows corresponding to the basal oxygen uptake. Our own clinical
      experience, gained in the last six months from a trial involving over 1,800
      patients, shows that the increase in opioid consumption resulted in additional
      costs of about 0.25-0.50 DM per patient. The increased concentration of
      inhalational agents brought additional costs of 3.00 to 5.00 DM for a two-hour
      anaesthesia. On the other hand, doing without nitrous oxide saved 2.61 DM per one
      hour anaesthesia, whereby our consumption of nitrous oxide is extremely low as
      minimal flow anaesthesia is performed consistently. Furthermore, these
      calculations disregard the cost of the technical maintenance fo the central gas
      piping system and of the regular measurement of workplace contamination with
      nitrous oxide by a certified institute, which in Germany, ad least, is
      obligatory. The additional costs of nitrous oxide-free inhalational anaesthesia
      seem to be balanced by the savings. Given the numerous justified arguments
      against the routine use of nitrous oxide, the lack of precisely-defined
      indications and the clinical experience showing that doing without nitrous oxide
      is uncomplicated, self-financing and ecologically beneficial, the use of nitrous
      oxide should be given up completely.

PMID- 10920483
TI  - [Effect of normobaric hyperoxia on parameters of brain metabolism].
AB  - In the literature there is only little information about the influence of
      hyperoxia on cerebral metabolic parameters. The aim of our study was to examine
      the effect of increased inspiratory oxygen concentrations on parameters of brain
      metabolism in elective neurosurgical patients. Ten patients undergoing an
      elective craniotomy for brain tumour resection were included in the study. The
      inspiratory oxygen concentration was raised at intervals of 15 minutes from 0.4
      to 0.6 to 1.0 before opening the skull under "relative steady state conditions".
      At five defined measuring points, a blood gas analysis and an analysis of lactate
      and glucose levels were performed from arterial and jugularvenous blood. The
      lactate oxygen index (LOI), the arterio-jugularvenous lactate difference (AJDL)
      and the oxygen content of the arterial (caO2) and jugularvenous (cjO2) blood were
      calculated. Under increasing levels of FiO2, one can see an increase in sjO2, of
      jugularvenous oxygen tension (pjO2) and in oxygen content (cjO2). The most
      important result is the significant decrease (10% from baseline) in jugularvenous
      lactate at FiO2 1.0, while arterial lactate did not change significantly nor did
      the following parameters: paCO2, pjCO2, LOI, modified LOI, arterial and
      jugularvenous glucose. Hyperoxia causes a possible shift to aerobic metabolic
      situation in the brain reflected by decreased jugularvenous lactate.

PMID- 10920484
TI  - [Carbon monoxide poisoning].
AB  - Carbon monoxide (CO) is a product of incomplete burning of coals and carbon
      compounds and is a gas without any typical taste, colour or smell. Defective
      radiators or gas pipes, open fireplaces, fires and explosions are sources of
      unintended CO production and inhalation. CO bonds with haemoglobin much more
      readily than oxygen does. CO toxicity causes impaired oxygen delivery and
      utilisation at cellular level. It affects different sites within the body, but
      has its most profound impact on the organs with the highest oxygen requirement.
      CO concentration and the intensity and duration of inhalation determine the
      extent of intoxication. Following basic life support, assisted or controlled
      ventilation with 100% oxygen is essential during emergency care. Hyperbaric
      oxygenation (HBO) is the preferred therapeutic option for releasing CO from its
      binding to haemoglobin. It has been shown that CO may cause lipid peroxidation
      and leukocyte-mediated inflammatory changes in the brain, a process that may be
      inhibited by HBO. Patients with neurological symptoms including loss of
      consciousness and expectant mothers should undergo HBO treatment, no matter how
      high their CO levels are. Neonates and in-utero fetuses are more vulnerable due
      to the natural leftward shift of the dissociation curve of fetal haemoglobin, a
      lower baseline pO2 and carboxyhaemoglobin levels at equilibration that are 10-15%
      higher than maternal levels. Physicians need to be aware of the potential
      occurrence of this life threatening hazard so that appropriate emergency
      treatment can be administered and fatalities prevented.

PMID- 10920485
TI  - [Paul Sudeck--his contribution to anesthesia].
AB  - Paul Sudeck is not generally recognised as a pioneer in anaesthesia, although he
      is well known for the atrophy of bone named after him. However, he not only
      championed the use of ether as a safe anaesthetic agent, described a method of
      ether analgesia for outpatient surgery and devised an inhaler for its
      administration, but also reintroduced nitrous oxide into Germany and invented
      possibly the first circle carbon dioxide absorption system with an optional
      attachment for continuous positive pressure respiration useful for the
      performance of thoracotomies.

PMID- 10920486
TI  - Current management of male breast cancer.
AB  - Male breast cancer represent 1% of all male cancers. The authors, by a review of
      literature, analyze risk factors and genic mutations involved in the development
      of such cancer. They discuss instrumental procedures of diagnosis and screening,
      histologic features and surgical approach of male breast cancer. Furthermore,
      they suggest adjuvant therapies stressing the importance of an early diagnosis
      and of the absence of nodal involvement to improve the outcome of male breast
      cancer.

PMID- 10920487
TI  - [Sentinel lymph nodes in skin melanoma].
AB  - BACKGROUND: Early node dissection offers increased survival in patients with node
      metastases only. The study of sentinel node (SN) using blue dye and
      radiolocalization permits to identify patients who could undergo lymphadenectomy.
      METHODS: At Department of Surgery of Macerata General Hospital 22 patients with
      melanoma of trunk or limbs at I and II stage were submitted to SN biopsy.
      RESULTS: SN was identified in all cases by combined approach. Dynamic
      lymphoscintigraphy permitted identification of SL when it was not the node
      nearest the tumor. Nodal metastases were found in 2 cases (9.1%) and the patients
      underwent regional lymphadenectomy. In 1 patient the SN was the only node with
      metastases. Both patients had high thickness melanomas. The measurement of
      radioactive exposition for operating room personnel and pathologist demonstrated
      that the technique is safe and without risks. CONCLUSIONS: Biopsy of SN is
      effective for identification of occult nodal metastases from cutaneous melanoma.
      Combined technique allows to localize SN in 100% of cases. There is not radio
      exposition for operators.

PMID- 10920488
TI  - Therapeutic indications for autonomous adenoma of the thyroid: 71 cases.
AB  - The Authors, on the basis of personal experience relative to 71 cases of
      Autonomous Adenoma of the thyroid treated by surgery or percutaneous ethanol
      injections (PEI), analyze the results in terms of complications and function.
      After comparing their results with the data in the literature relative to
      radioiodine therapy, the Authors conclude that surgery should be the primary
      treatment for plurifocal nodules or nodules greater than 2 cm in diameter, while
      PEI can be used for single nodules smaller than 2 cm. The point is that
      radioiodine often induces hypothyroidism, while our knowledge of the results of
      percutaneous ethanol injections is still limited in terms of number of cases and
      length of observation periods. Therefore, the authors think that the treatment of
      Autonomous Adenomas should be surgical, while non-surgical therapy should be
      limited to specific cases (dimensions, age, or general contraindications to the
      operation).

PMID- 10920489
TI  - [Videothoracoscopy in the diagnosis and treatment of hemothorax].
AB  - Video assisted thoracic surgery (VATS) has assumed greater importance in the
      management of pleural diseases. From 1994 to 1998 the Authors report their
      experience about 11 cases of hemothoraces depending on various causes: 6
      hemothoraces and 3 hemopneumothoraces, some spontaneous or iatrogenic, others in
      patients with chest trauma; 2 clotted hemothoraces. All patients were studied by
      VAT detecting the source of bleeding in 6 cases of acute hemothorax and in 3
      cases of acute hemopneumothorax; in 5 cases the lesions were successfully
      repaired with thoracoscopic technique. In others 4 patients the VATS approach was
      converted to thoracotomy for the seriousness of lesions: 3 acute hemothoraces (1
      patient with penetrating thoracic firearms injury, 1 patient with extended lung
      laceration, 1 patient with iatrogenic lesion of right subclavian artery); 1 acute
      hemopneumothorax in one patient with penetrating thoracic firearms injury and
      left hemidiaphragmatic double perforation: in this case laparotomy was also
      operated in order to exclude others abdominal lesions. 2 cases of clotted
      hemothorax were operated by VATS performing the removal of clots after their
      fragmentation by endobabcock and pleural irrigation-aspiration with physiological
      solution. No procedure related complications were occurred. The authors conclude
      that the video-thoracoscopic approach is certainly advantageous for the
      management of spontaneous, traumatic or iatrogenic acute hemothoraces. This
      technique permits, with minimal traumatism and very little complications, the
      correct therapeutic programming (VATS operation or conversion to thoracotomy).
      However some hemothoraces (hemothoraces in patients with serious cranial trauma,
      with spleen rupture, with great vessels rupture, with heart rupture or with
      massive post-operating hemothorax) contro-indicate the thoracoscopic treatment:
      immediate thoracotomy and/or laparotomy, in these cases, is indispensable. In the
      treatment of clotted hemothoraces the VATS is a favourable alternative to
      thoracotomy, reforming the pleural cavity with minimal traumatism and avoiding
      tardive complications.

PMID- 10920491
TI  - [Echolaparoscopy in the staging of abdominal neoplasms. Prospective study].
AB  - OBJECTIVE: To evaluate the sensitivity, specificity, positive and negative
      predictive value and influence on surgical strategy of laparoscopy and
      laparoscopic ultrasound on staging of abdominal malignancies. MATERIAL AND
      METHODS: Prospective evaluation of laparoscopic ultrasound staging, according to
      the TNM classification, of 80 consecutive cases of abdominal malignancies in
      terms of sensitivity, specificity, positive and negative predictive value and
      influence on surgical strategy. Pathologic examination of final surgical
      specimens or laparoscopic biopsies was used as control. RESULTS: Laparoscopic
      ultrasound evaluation was carried out successfully in 95% of cases with no
      mortality and morbidity. Twenty one out of 76 patients (28%) had their stage
      changed based on laparoscopic ultrasound findings. Unnecessary laparotomy was
      avoided in 11 cases (14%) due to evidence of advanced disease at laparoscopic
      ultrasound. For pancreatic cancer laparoscopic ultrasound was more sensitive for
      TNM, specificity was higher just for nodal evaluation. For liver tumor
      laparoscopic staging revealed more sensitive for N and M evaluation. Laparoscopic
      ultrasound staging had low specificity and sensitivity for T evaluation, while it
      was more sensitive and specific than clinical staging for nodal and distant
      metastasis assessment respectively for gastric and colon cancer. CONCLUSION:
      Laparoscopic ultrasound staging is a safe, feasible and effective staging tool
      for several abdominal malignancies. The introduction of laparoscopic ultrasound
      probes overcomes the lack of tactile sensation proper of laparoscopy, allowing
      precise evaluation of both solid and deeply located abdominal structures. The use
      of laparoscopic ultrasound staging may help to reduce the number of unnecessary
      laparotomies.

PMID- 10920490
TI  - [Emergencies in gastroesophageal varices hemorrhage in the patient with portal
      hypertension].
AB  - High gastrointestinal hemorrhage represents the more frequent (12-71.1%) and
      heavy complication of hepatic cirrhosis and correlates to portal hypertension; it
      is weighed by global mortality which sways from 30 to 50%. High gastrointestinal
      hemorrhage gives, therefore, a serious of diagnostic and therapeutic problems not
      easy to guide for at least 3 reasons: numerous causes of bleeding; hepatic
      failure; the marigold possible therapies. Aim of this work is to clarify some
      diagnostic and therapeutic features about high gastrointestinal hemorrhage in
      cirrhotic patient, because such eventuality often presents dramatic aspects,
      which endangers the patient's life. Our experience shows a casuistry referred to
      the period of time which goes from 1987 to 1998 and that comprehend 143 examined
      patients: 91 of theme have been submitted to medical treatment (endoscopic
      sclerotherapy, glupressin e/o somatostatin); in 52 cases it has been possible to
      realize a surgical treatment, different from the elective therapy (33 pz) and
      emergency therapy. Immediate hemostatic effect obtained in both the conditions,
      has been satisfying with best results at a distance of three years and five years
      given by devascularization. As matter stands our preference of the
      devascularization surgical treatment, it seems appropriate to pay attention to
      the operation of mesocaval anastomosis which, either in Our very brief experience
      (3 cases) or by international literature, seems to offer encouraging results.

PMID- 10920492
TI  - [Our experience with pheochromocytoma].
AB  - The authors report cases of pheocromocytomas operated in the period 1991-1997. 16
      of these patients presented a monolateral pheocromocytoma, 1 a bilateral. A
      patient had a malignant evolution, one patient presented an extrasurrenal para
      aortic localization. All the patients were operated by a middle longitudinal
      laparotomy. There was no mortality, neither significant morbility. In all the
      patients, who presented pre-operatory arterial hypertension, there was a
      regression of the symptomatology.

PMID- 10920493
TI  - The role of surgical treatment in colon diverticulitis: indications and results.
AB  - PURPOSE: Colon diverticulitis is a common illness with affects 37-45% of western
      populations. Indications regarding therapy guidelines, operative timing and which
      surgical procedure to perform are still controversial. MATERIAL AND METHOD:
      Between January 1977 and December 1997, 239 patients, diagnosed with
      diverticulitis, have been admitted, on emergency, to our Department of General
      Surgery; 135 males (56%) and 104 females (44%), (mean age of 63 years). RESULTS
      AND DISCUSSION: Forty-two patients (18%), clearly diagnosed with diffuse or local
      peritonitis, underwent delayed emergency surgical procedure; 44 (22%) out of 197
      patients, treated with medical therapy and subsequently underwent elective
      surgery procedures for complications (fistulas or stenosis). Among the 42
      patients treated in emergency, 26 cases (62%) underwent to resection with
      immediate reconstruction. Among the elective surgery group 39 (89%) out of 44
      underwent to resection with immediate reconstruction. Complications reached 40%
      in the group of emergency patients (mortality rate 12%) and 16% in the elective
      surgery group (mortality rate 2%). Several features possible influencing
      mortality rate have been analysed; age > 70 years, acute associated diseases,
      generalised peritonitis and surgical timing show a statistical significance.
      CONCLUSION: Therefore, a careful evaluation of the patients, an appropriate pre
      and post-operative medical treatment, with a wider use of the most recent
      techniques such as CT scan guided drain, intra-operative wash-out and peritoneal
      lavage are recommended in order to reduce morbidity and mortality.

PMID- 10920494
TI  - [Non-polyposis colorectal cancer in subjects under 55 years of age: frequency and
      phenotype of hereditary or familial syndromes].
AB  - Young age is believed to be a risk factor for hereditary or familial non
      polyposis colorectal cancer. Present study analysed frequency, phenotype and
      familial cancer risk of 82 subjects with colorectal cancer under 55 years of age.
      According to age and family history, probands have been subdivided into 5 groups:
      Hereditary Non-Polyposis Colorectal Cancer (HNPCC) (8.2% of cases); Suspected
      HNPCC (7.3%); Non-specific familial aggregation of colorectal cancer (AFACC)
      (19.5%); Early-onset colorectal cancer (diagnosis under 35 years of age) (CCG)
      (6.1%); Sporadic colorectal cancer (CCS) (58.5%). Proportions of probands with
      multiple colonic tumours were highest in HNPCC (57.1%), but present in AFACC
      (12.5%) and CCG (20.0%) groups, as well. Extracolonic, in particular endometrial
      and ovarian cancers have been found in HNPCC and AFACC probands. Tumours of
      proximal colon were most frequent in HNPCC, suspected HNPCC, CCG patients. Eleven
      years survival rate was higher in HNPCC probands then in CCS group. Familial
      cancer risk in HNPCC was 3 times as much as in CCG + CCS groups. Diagnosis of
      colorectal cancer under 55 years of age is associated with an high frequency of
      hereditary or familial cases. Genetic tests, surveillance and screening programs
      in these patients must be based on extensive phenotype and pedigree analyses.
      HNPCC is widely represented in young colorectal cancer patients and is associated
      with a high risk of multiple synchronous or metacronous colonic and extracolonic
      tumours. Total colectomy and eventual hysterectomy with bilateral oophorectomy
      seem therefore recommendable options in these patients.

PMID- 10920495
TI  - [Evolution of the surgical treatment of rectal cancer. Our experience].
AB  - In this study we have reviewed our data from 1973 to 1998 and we have compared
      three intervals. In each of these periods we have performed the same type of
      surgery which enables the comparison of adopted techniques with obtained results.
      During the first period (1973-1980) we have treated 65 cases of rectum cancer
      staging between B2 and D, which were mainly localised in the medium rectum
      (41.2%). During the second period (1981-1990) we have treated 44 cases with a
      majority of patients staging B2. The localisation was again mainly in the medium
      rectum (38.5%). During the third period (1981-1998) we have treated 37 cases of
      rectum cancer staging between A2 and B1. Again the most frequent site was the
      medium rectum (48.9%). Consequently, we compared the staging, the type of surgery
      and the complications for the three periods. Our results show that the survival
      time was 5 years, in 70% of the cases where an anterior resection was performed,
      but this percentage decreased substantially if we also considered patients
      presenting with an advanced staging (C2-D), in which the only type of surgery
      that could be performed was colostomy or the simple explorative laparotomy.

PMID- 10920496
TI  - [Blood levels of cholesterol and postoperative septic complications].
AB  - Hypocholesterolemia seems to represent a significant predictive factor of
      morbidity and mortality in critically ill patients. The authors, on the basis of
      recent literature data, aim to clarify the possible correlation between
      preoperative hypocholesterolemia and the risk of septic postoperative
      complications .205 patients undergoing to surgery for gastrointestinal diseases
      were the object of the study. Patients undergoing "minor" abdominal surgery or
      video-laparoscopic surgery and classified ASA III-IV were excluded. In all the
      patients, we considered retrospectively risk factors for postoperative septic
      complications as follows: preoperative blood concentration of cholesterol,
      malnutrition, obesity, diabetes, neoplasm, preoperative sepsis, type and duration
      of operations, antibiotics and regimen of use. Type and incidence of
      postoperative local or systemic septic complications were recorded. The patients
      have been stratified according to blood concentration of cholesterol and to the
      presence or absence of other risk factors. The incidence of postoperative sepsis
      was 35.1%. The highest incidence of postoperative septic complications (72.7%)
      was encountered, significantly (X2 = 7.6, p < 0.001), in the patients (11 cases,
      5.9%) with cholesterol levels below 105 mg/dl). The results of this study seems
      to indicate a significant relationship between preoperative hypocholesterolemia
      and the incidence of septic complications after surgery. Moreover, evaluation of
      blood cholesterol levels before major surgery might represent a predictive factor
      of septic risk in the postoperative period.

PMID- 10920497
TI  - [Assessment of conventional approaches in adrenalectomy].
AB  - The choice of operative approach represents one of the main problems of adrenal
      gland surgery, nowadays the minimally invasive techniques (laparoscopic
      adrenalectomy) in selected cases may be an important alternative to conventional
      approaches. Retrospective analysis was performed on 140 patients with adrenal
      gland tumors from 1980-1997; there were 95 women and 45 men: The tumors were
      resected through flank extraperitoneal approach (35 patients), transabdominal
      (91), thoraco-abdominal (14). Operating time, perioperative blood loss,
      postoperative course were evaluated. The authors conclude that in functioning and
      non-functioning adenomas, in pheochromocytoma, smaller than 6 cm., with precise
      pre-operative unilateral localization, flank extraperitoneal approach may be
      sufficient, in patients with Cushing disease resistant to pituitary surgery or
      irradiation, in patients with familiar history or bilateral pheochromocytoma, in
      patients with suspected malignant disease, a thorough surgical exploration of the
      abdominal cavity is recommended.

PMID- 10920498
TI  - [Chronic rupture of abdominal aortic aneurysms. (Report of 3 cases)].
AB  - Rupture of an abdominal aortic aneurysm often presents with an abdominal pain,
      hypotension and a pulsatile abdominal mass. In the last years same clinical
      reports describe patients with less apparent clinical signs who were found later
      in their evaluation to have a contained rupture of an abdominal aortic aneurysm.
      The diagnosis may be delayed by consideration of other disease causing similar
      symptoms (herniated disc, renal colic). In these patients with confusing
      abdominal symptoms CT scan provides a rapid and noninvasive diagnosis. We report
      three cases of contained rupture of an abdominal aortic aneurysm evaluated by
      computed tomography with different clinical presentation: back pain for erosion
      into the lumbar vertebral bodies, lower extremity neuropathy and obstructive
      jaundice. All patients were operated on within 24 hours on admission; there was
      no operative mortality and survival was 100% at one year.

PMID- 10920499
TI  - [Splenic artery rupture in pancreatic pseudocyst].
AB  - Hemorrhage is one of the most threatening complication of pancreatic pseudocyst.
      It results from erosion of adjacent vessels. Splenic, gastroduodenal,
      pancreaticoduodenal and middle colic vessels are predominantly involved.
      Hemorrhage may present different feature: intra and/or extraperitoneal
      collection, gastrointestinal bleeding. The authors report the rupture of splenic
      artery into pseudocyst, with the formation of pulsating pseudoaneurysm,
      increasing progressively until the final rupture. For the diagnosis the authors
      utilized: ultrasounds (US) which showed the cyst but not its nature and content;
      the CT scan which disclosed haematic contents; finally the US Color Doppler which
      proved the dynamic feature of hemorrhage. This technique allows to identify the
      arterious or venous source of bleeding and the possible presence of arteriovenous
      fistula. Arteriography was not performed due to circumstances, although it would
      permit bleeding vessel embolization and the control of hemorrhage. This procedure
      is not ever achievable, and doesn't exclude the possibility of rebleeding. On
      surgery, since the intraoperative rupture of the pseudoaneurysm occurred with
      severe hypovolemic shock, only a timely posterior mesogastric mobilization and
      the medially displacement of spleen-body-tail pancreatic complex, allowed to
      clamp the mass and the hemostasis. When such lesion are approached, it is
      mandatory to be prepared to carry on this maneuver: the severity of bleeding
      cannot allow intracystic ligature of bleeding vessel.

PMID- 10920500
TI  - [TC-99m-pertechnetate scintigraphy in the diagnosis of abdominal diseases].
AB  - OBJECTIVE: To show the possible role of abdominal scintigraphy in the diagnosis
      of intra-abdominal pathology and its accuracy in detecting ectopic gastric mucosa
      in pts with intestinal bleeding and/or abdominal pain. METHOD: 99m-Tc
      pertechnetate scintigraphy was performed on 54 pts with a history of intestinal
      bleeding and/or abdominal pain with the following results: 11 true positive pts
      (9 with Meckel's D; 2 with enteric duplication) all of whom were confirmed at
      surgery; 14 false positive pts in whom the presence and location of entero-colic
      (12 pts), renal (2 pts), and uterine (1 pt) pathology were determined; 28 true
      negative pts; an arca of persistent low activity was found in the bladder of 1 pt
      which later proved to be a ureterocele at ultrasound; 1 false negative pt who was
      found to have Meckel's D at surgery. CONCLUSION: In this case series abdominal
      scintigraphy was effective in diagnosing 26/54 pts and, in particular, in
      diagnosis, 23/28 pts in recurrent intestinal bleeding. Given that its sensitivity
      is not negligible and that it is an exam which is scarcely invasive, easy to
      perform and interpret and requires low irradiation (definitely lower than barium
      enemas, digestive tract radiography and CT), abdominal scintigraphy should be the
      first examination to be performed in all pts with intestinal bleeding and/or
      abdominal pain, especially children, whose diagnosis cannot be simply or rapidly
      determined.

PMID- 10920501
TI  - [Hepatitis C virus and iron overload: beware of these two!].

PMID- 10920502
TI  - [Severe alpha 1-antitrypsin deficiency: cross sectional clinical study].
AB  - The aim of this study was to investigate a group of severe alpha 1-antitrypsin
      deficient subjects. Of the 20 subjects detected, 7 were classified as Index Cases
      (discovered because they were symptomatic and had pulmonary emphysema or liver
      disease), while 13 were classified as Non-Index Cases (asymptomatic and
      discovered because they were relatives of Index Cases or because of the absence
      of alpha 1 band in serum electrophoresis). They underwent pulmonary function
      tests, determination of arterial blood gases, lung high resolution computed
      tomography and lung perfusion scan. All Index Cases were with the ZZ phenotype,
      indicating a major risk of developing related pulmonary emphysema or liver
      disease; most Index Cases (71%) were ex-smokers, while among the Non-Index Cases,
      46% were smokers or ex-smokers, suggesting that smoking might be the main
      cofactor in the development of emphysema. Index Cases were older (statistical
      significance) and mostly male as compared with Non-Index Cases. A statistical
      significance was observed between the two groups for several lung function
      parameters (forced expiratory volume in one second, Tiffenau index, residual
      volume, diffusing capacity of the lung for carbon monoxide, arterial oxygen
      tension) as a result of a pathological impairment in Index Cases. This
      underdiagnosed condition merits more attention in order to prevent its
      complications and to get a better understanding about its diagnosis and
      management.

PMID- 10920503
TI  - [Effect of iron depletion on long-term response to interferon in patients with
      chronic hepatitis C with increased plasma iron without accumulation of liver
      iron].
AB  - We studied the effect of iron depletion on the response to subsequent interferon
      therapy in a population of 83 patients affected by chronic hepatitis C who had
      not previously undergone any specific therapy and who had laboratory confirmation
      of iron overload (serum ferritin > 400 ng/mL in the males and > 300 ng/mL in the
      females). The population was divided into two homogeneous groups. Group A
      consisted of 43 patients who underwent phlebotomy (300 mL every 10-15 days for an
      average total of 8 sessions) until serum ferritin levels of < 100 ng/mL were
      obtained. The 40 patients in Group B were treated with interferon without prior
      iron depletion. Iron depletion alone, induced in Group A, brought about a highly
      significant (p < 0.01) reduction of alanine aminotransferase serum values: from
      165 U/L (range 60-370 U/L) to 67 U/L (range 27-158 U/L). Seventy-six patients
      completed therapy and follow-up: a complete and sustained response was obtained
      in 12/39 cases in Group A and in 6/37 cases in Group B (p < 0.05). Iron depletion
      carried out in patients with chronic hepatitis C, who have elevated base values
      of serum ferritin, induces a significant reduction in necro-inflammatory activity
      (notable decrease in average alanine aminotransferase values) and improves the
      response to subsequent treatment with interferon, although it does not modify the
      viral load.

PMID- 10920504
TI  - [Oral anticoagulants and medicinal plants. An emerging interaction].
AB  - The consumption of herbal medicines is increasing steadily throughout the world,
      although to our knowledge there are neither studies on their effectiveness nor
      controls over the quality and safety of these preparations. Considered "food
      integrators", these preparations are marketed without restriction. It is a common
      notion that natural therapy has neither side nor toxic effects: allergic
      reactions, direct toxic effects or those due to contamination, carcinogenicity,
      mutagenicity, and heavy metal toxicity have been reported as adverse events
      caused by herbs. Rather than replacing traditional therapy, most herbal medical
      treatment is used in conjunction with it. Also, the attending physician is
      generally not informed that the patient is using herbs. Because Passionflower,
      hydroalcoholic extracts, Juniper and Verbena officinalis supply variable
      quantities of vitamin K, they can lessen the effect of oral anticoagulant
      therapy. Ganoderma Japonicum, Papaw, Salvia miltiorrhiza, Ginseng, Devil's claw,
      Garlic, Quinine, Ginkgo, Ginger, Red Clover and Horse-Chestnut reinforce warfarin
      action by heterogeneous mechanisms. They should thus not be used in patients on
      oral anticoagulant and/or antiplatelet therapy. The scientific community must
      take into account the adverse events caused by interaction between herbal
      medicine and conventional therapy, and patients must be informed of the dangers
      of these preparations. If a bleeding event occurs or the quality of anticoagulant
      therapy is poor, the clinician should consider the possibility of interaction
      between conventional therapy and herbal medicine that the patient has neglected
      to mention he is taking.

PMID- 10920505
TI  - Infections, atherosclerosis, and coronary heart disease.
AB  - There is growing evidence that the immune response is involved in
      atherosclerosis. Studies done over the past several years have shown an
      association between markers of inflammation and coronary atherosclerosis with an
      exacerbation of the inflammatory process during acute myocardial ischemia.
      Overall, these data have greatly renewed interest in the infectious theory of
      atherosclerosis and coronary heart disease. Search of bibliographic databases
      (from January 1991 through December 1999) and manual scanning of both peer
      reviewed publications and other documents were used to identify pertinent
      literature. Infections and coronary heart disease were indexed as key words. A
      large number of studies have reported an association of human coronary heart
      disease and certain persistent bacterial and viral infections. The association
      between Chlamydia pneumoniae and coronary heart disease appears quite significant
      although the sequence of infection and disease is uncertain. The association
      between Helicobacter pylori and coronary heart disease may be accounted for by
      residual confounding from classic risk factors. Preliminary findings indicate
      that this association could be due to a higher prevalence of more virulent
      Helicobacter strains. Infection with Cytomegalovirus appears to be associated
      with a greater risk of restenosis after angioplasty rather than primary
      atherosclerosis. Early trials of appropriate antibiotic therapy in subjects with
      recent acute myocardial infarction have been encouraging. A causal relationship
      between infections and coronary heart disease is still elusive. Improved studies
      involving prospective collection of data are required to demonstrate such an
      association with potential implications for public health worldwide.

PMID- 10920506
TI  - [Venous thromboembolism and neoplasms].
AB  - Venous thromboembolism, including deep vein thrombosis and pulmonary embolism, is
      a major cause of morbidity and mortality. In most cases, one or more risk factors
      for removable or persistent venous thromboembolism can be identified. Persistent
      risk factors include inherited or acquired abnormalities of the hemostatic system
      and cancer. As Armand Trousseau first suggested, venous thromboembolism may be
      the first clinical manifestation of an occult cancer. This relationship has
      recently been confirmed by methodologically well designed studies. Furthermore,
      venous thromboembolism is the second cause of death in patients with clinically
      overt cancer. This review summarizes the state of the art of this association.
      The clinical trials described focus on the need to perform screening for occult
      cancer in patients with idiopathic venous thromboembolism. How extensive this
      screening should be is still matter of debate. On the other hand, patients with
      clinically overt cancer should be considered at high risk for developing venous
      thromboembolism, and adequate prophylaxis should be used.

PMID- 10920507
TI  - [A case of acute recurrent benign pericarditis in a patient with glucose-6
      phosphate dehydrogenase deficiency, treated with sodium salicylate].
AB  - Glucose 6-phosphate dehydrogenase deficiency is an important cause of hemolysis.
      People with this disease are prone to hemolytic crisis induced by drugs,
      including acetylsalicylic acid. Sodium salicylate is the main therapeutic choice
      for acute idiopathic pericarditis. In vitro studies have demonstrated the role
      played by sodium salicylate in the inhibition of glucose 6-phosphate
      dehydrogenase, but, at therapeutic doses, this inhibition is not enough to
      explain acetylsalicylic acid-induced hemolysis observed in vivo. We thus treated
      a patient affected by acute idiopathic pericarditis and glucose 6-phosphate
      dehydrogenase deficiency with sodium salicylate, obtaining complete resolution of
      fever and symptoms, without any hemolytic complication. Therapy with sodium
      salicylate could thus be a safe and effective alternative for patients with
      glucose 6-phosphate dehydrogenase who require anti-inflammatory therapy.

PMID- 10920508
TI  - Liposomal amphotericin B as first line and secondary prophylactic treatment for
      visceral leishmaniasis in a patient infected with HIV.
AB  - Visceral leishmaniasis has emerged in both endemic and non-endemic areas as an
      opportunistic infection in HIV-positive subjects. At risk for infection are HIV
      positive intravenous drug abusers with a low CD4 T cell count and a high HIV
      viral load. In these patients, who are not always symptomatic, leishmaniasis is
      probably due to endogenous reactivation and often presents in an atypical
      fashion. Death results from uncontrolled bleeding or bacterial infections. The
      clinical and biological spectrum of this disease suggests that it should be
      included among the diagnostic criteria for AIDS. Visceral leishmaniasis responds
      poorly to therapy and, when responsive, the relapse rate is high. Treatment
      protocols and criteria to document cure after treatment have not been definitely
      established. Lastly, there is no effective immuno- or chemo-prophylaxis against
      this protozoan. We report the case of an HIV-infected patient affected by
      visceral leishmaniasis who was successfully treated with liposomal amphotericin B
      given both as first line and as secondary prophylactic therapy. The patient has
      remained disease-free for 26 months after his first remission whereas, to our
      knowledge, almost all immunocompromised patients relapse within 12 months.

PMID- 10920510
TI  - [Hard and soft medicine: 2 weights, or no weight, to assess the contributions].

PMID- 10920511
TI  - [New perspectives in the assessment of primary care: qualitative methodologies].

PMID- 10920509
TI  - Acquired factor VIII inhibitor associated with prostatic cancer: successful
      treatment with steroid and immunosuppressive therapy.
AB  - Factor VIII inhibitors are antibodies of the IgG class that block functional
      epitopes or antigenic sites of factor VIII. They occur in about 5-20% of
      hemophilia A patients after infusions of factor VIII concentrate. Antibodies to
      factor VIII can also arise spontaneously in association with various autoimmune
      and chronic inflammatory diseases, hematologic malignancies, solid tumors,
      certain drugs, dermatologic conditions, and in puerperium. In the majority of
      cases, the clinical course is characterized by severe hemorrhages. Strategies to
      treat such inhibitors are controversial. We present the case of a patient with
      prostatic cancer who developed acquired factor VIII inhibitor. His severe
      bleeding complications were treated successfully with cyclophosphamide in
      combination with methylprednisolone. Within a few months, moreover, the
      immunosuppressive therapy brought about complete disappearance of the inhibitor
      and normalization of coagulation parameters. Our case illustrates that, although
      the clinical course in patients with acquired factor VIII inhibitor is not
      predictable, and the inhibitor may disappear spontaneously, combined therapy with
      cyclophosphamide and methylprednisolone should be considered for patients with
      severe hemorrhages.

PMID- 10920512
TI  - [Vaccination of adults: significance of the schedule. Group for Infectious
      Diseases of the PAPPS. Program of Preventive Activities and Health Promotion].

PMID- 10920513
TI  - [Alcohol consumption among students of the autonomous community of Extremadura].
AB  - OBJECTIVES: To find the number of drinkers, the relationship of their environment
      to the habit and attitudes to alcohol of Estremaduran children in the eighth year
      of EGB/second of ESO. DESIGN: Crossover descriptive study of a representative
      sample of the students in these school years. SETTING: All the schools in our
      autonomous community. PARTICIPANTS: 996 students belonging to various educational
      establishments. MEASUREMENTS AND MAIN RESULTS: We used a self-filled
      questionnaire with questions on the alcohol consumption of those being surveyed
      and their parents, siblings, friends and teachers. Other variables such as age,
      sex, parents' educational qualifications and other questions touching on the
      attitude to alcohol were included too. The subjects were 13-14 years old (54%
      boys and 46% girls). 15.50% were habitual drinkers and 54.43% occasional
      drinkers, with the number of boys predominating in the two groups (72.72 against
      27.27% and 54.07 against 45.93%, respectively). Consumption was clearly higher in
      the father, siblings and friends of habitual drinkers (p < 0.05, p < 0.001 and p
      < 0.001, respectively). Parents of non-drinkers had higher educational
      qualifications. Habitual drinkers, and to a lesser degree occasional drinkers,
      displayed favourable attitudes to consumption and a positive association with
      alcohol consumption. CONCLUSION: Given their age, the percentage of drinkers is
      worrying and is linked to the presence of the habit in their closest social
      environment. The positive attitudes to alcohol consumption of our school students
      justify the introduction of prevention programmes.

PMID- 10920514
TI  - [Factors associated with arterial distensibility in hypertension].
AB  - OBJECTIVE: To find out what variables affect changes in arterial compliance in
      subjects with hypertension by measuring their pulse wave velocity (PWV). DESIGN:
      Cross-sectional, descriptive study. SETTING: Rural health centre. PATIENTS: 156
      hypertense patients under 76, chosen by simple random sampling from those on the
      hypertension register. MEASUREMENTS AND INTERVENTIONS: We determined the degree
      of hypertension, years of evolution, systolic pressure (SBP), diastolic pressure
      (DBP), body mass index (BMI), glucaemia, whether lipaemia existed, diabetes or
      glucose intolerance, tobacco habit, age, sex and PWV (measured automatically by
      computer). We performed multivariate analysis by means of multiple linear
      regression, with PWV as the dependent variable, and age, SBP, DBP, BMI, years of
      evolution of hypertension, cholesterol, triglycerides and glucaemia as
      independent variables. RESULTS: Mean age 62.5 (SD 8.8). 28.2% male. Mean SBP 153
      (SD 18.9). Mean DBP 87 (SD 10.3). Mean years of evolution 10.4 (SD 7.4). Mean BMI
      31.2 (SD 4.9). Hyperglucaemia 24.4%. Mean glucaemia 111.3 (SD 29). Mean PWV 11.82
      (SD 2.37). PWV was above the theoretically normal figures in 69.2% of cases.
      Multiple linear regression showed that the variables which affected PWV
      significantly were age, SBP and hyperglucaemia. CONCLUSIONS: Arterial compliance
      can be improved by controlling SBP, given that the other related factors cannot
      be changed.

PMID- 10920515
TI  - [Analysis of drug consumption with indicators of prescription quality].
AB  - OBJECTIVE: To evaluate the quality of pharmaceutical prescription by means of
      various indicators. DESIGN: Cross-sectional, retrospective study. SETTING: Non
      hospital prescription in all the INSALUD provinces, except Ceuta and Melilla, for
      a year (1997). MEASUREMENTS: Different quality indicators were analysed for the
      following groups of medicines: oral diabetes drugs, anti-platelet aggregation
      drugs, anti-hypertension drugs, non-steroidal anti-inflammatories, tranquillisers
      and hypnotic drugs, antibiotics, anti-asthmatic drugs and the omeprazol
      efficiency indicator. Consumption was expressed in defined daily doses (DDD) and
      in DDD per 1000 persons and per day (DID). A prescription quality indicator was
      indicated on the basis of weighing up the indicators. RESULTS: The sulphonylurea
      drugs varied greatly (15-56%) and deviated negatively a lot from the standard
      value. AAS and ticlopidine made up 74% of the anti-platelet aggregation drugs.
      Consumption of calcium antagonists was three times greater than of beta-blockers.
      Captopril and enalapril were 65% of the ACE inhibitors. Ibuprofen, naproxen and
      diclofenac made up between 34 and 50% of the NSAIDs. The DID of hypnotics was 44
      against a standard figure of 24. Use of first-level antibiotics was 77%. Inhaled
      adrenergic drugs came to 80% of total anti-asthmatic drugs. The cost of omeprazol
      treatment per day was 267 pesetas/DID, which was inefficient in comparison with
      the standard of 190. All provinces had a prescription quality indicator above six
      out of ten. CONCLUSIONS: The ACE inhibitors, anti-asthmatic drugs and antibiotics
      were close to the standard. The use of sulphonylurea drugs, beta-blockers, NSAIDs
      and hypnotics was a long way from standard. The prescription level was acceptable
      in the different provinces.

PMID- 10920516
TI  - [Informed consent at a primary care area].
AB  - OBJECTIVE: Assessment of the understanding and performance of informed consent by
      primary care doctors and people attending clinics (PAC) in Madrid Area 3. DESIGN:
      Descriptive cross-sectional study. SETTING: The 20 health centres in Madrid Area
      3. PARTICIPANTS: Doctors and PAC in Area 3. MEASUREMENTS AND MAIN RESULTS: It was
      a structured survey, validated by a pilot study. 98.7% of doctors stated that
      they informed their patients about illnesses; 91.8% on the risks and benefits.
      90.6% and 78.6%, respectively, of the PAC said they were informed. Although 86.8%
      (CI 83.7-89.9) of the PAC thought they understood the information transmitted
      well, only 61% (CI 53.4-68.6) of the doctors thought so. 60.4% of the doctors and
      54.6% of the PAC thought that the doctors' decisions took into account the
      patient's view. This was also the preferred option of both groups (46.5% and
      59.3%). 29% of the doctors preferred greater power of decision for the patients,
      and only 16.06% of the PAC. 91.6% (CI 89.1-94.1) of the PAC were satisfied with
      the information received. CONCLUSIONS: Doctors think they give information better
      than PAC think. Patients' understanding of the information is given a higher
      rating by the PAC than by the doctors. Decisions are habitually taken by the
      doctor, with the patient's views borne in mind. However, doctors would prefer
      patients to have greater decision-making power.

PMID- 10920517
TI  - [Application of a geriatric evaluation protocol in primary care: comparison with
      data from the clinical history].
AB  - OBJECTIVES: To determine the prevalence of the health problems included in a
      multidimensional geriatric assessment (MGA) protocol and to compare them with the
      problems detected in the clinical histories (CH) of the population consulting at
      a primary care centre (PCC). DESIGN: Cross-sectional observational. SETTING:
      Urban PCC (metropolitan area of Barcelona). PATIENTS: Users > or = 65 of a PCC
      between 01/11/97 and 31/01/98. MEASUREMENTS AND MAIN RESULTS: A random sample of
      114 people was chosen. The MGA protocol was used to screen disorders in: hearing,
      vision, mobility, affective state, cognitive state, social support, functionalism
      of the instrumental activities of daily life. The clinical histories provided
      age, sex and information previously recorded on these disorders. 102 people were
      surveyed (participation: 89.5%). The MGA enabled more problems to be detected,
      with the difference very marked in some cases such as visual disorders: 55.9%
      (46.2-65.5) with MGA and 23.5% (15.3-31.8) with CH. There was poor concordance
      between MGA and CH. For example, neither the 73.3% (54.1-87.7) of the hearing
      disorders detected with the MGA, nor 94.1% (71.3-99.8) of the cognitive
      deterioration detected with the MGA had been previously recorded in the CH.
      CONCLUSIONS: MGA detects more health problems than are normally recorded in
      primary care clinical histories, which makes this technique relevant to PC
      consultations with the elderly. However, it would be advisable to identify the
      population for whom there was better diagnostic performance.

PMID- 10920518
TI  - [Results of the application of a health test in a population of immigrants].
AB  - OBJECTIVE: To describe the demographic characteristics and the results of a
      healthcare exam of immigrants. DESIGN: A retrospective descriptive study.
      SETTING: Rural doctor office of Villafranca del Castillo. Madrid. PATIENTS: All
      immigrants (n = 76) that came for care between May of 1996 and May of 1998.
      INTERVENTIONS: History, physical exam and basic laboratory tests. RESULTS:
      Demographic data: 82% are women with a medium age of 33 years (SD 8.49). Their
      places of origin are Central America: 70%, Philippines: 20%, Africa: 5% and South
      America: 3%. 97% of them work as household employees or gardeners. They have been
      living in Spain for an average time of 56 months. Health data: 21.1% are smokers
      and 17.1% low risk drinkers. 64.5% lack tetanus vaccine and 11.8% lack both
      tetanus and rubeola vaccines. Serologic test for HBV are negative in 68.4%. 14.5%
      have past infection and there are no cases of chronic or active infection. PPD is
      over 10 mm in 35.5%, and between 5 and 10 mm in 7.9%. Prevalence of active TBC is
      0%. Stool culture is positive in 6.5%. Salmonella tiphy is identified in one
      case. Stool examination for ova and parasites is positive in 42.1% of the
      patients. Protozoos (88%) are more common than helminths (12%). CONCLUSIONS: This
      study reveals a selective young and healthy immigrant group. The low presence of
      hepatitis B and tuberculosis infections are notable. The majority present
      parasites in stool samples.

PMID- 10920519
TI  - [Evaluation of theory-practice knowledge on inhalation systems in primary care
      physicians, post-graduates in training and undergraduates].
AB  - OBJECTIVE: To find the theoretical and practical knowledge concerning inhalation
      systems of primary care doctors, postgraduates in training--family & community
      medicine (FCM) residents--and undergraduates who had passed their course in
      pneumology. DESIGN: Crossover, descriptive study. SETTING: FCM teaching unit of
      the Puerta del Mar Hospital (Cadiz), the Cadiz Faculty of Medicine and seven
      primary care centres on the Bay of Cadiz. PARTICIPANTS: 31 practising primary
      care doctors, 25 third-year FCM residents and 31 medical students were evaluated.
      MEASUREMENTS AND MAIN RESULTS: A thirteen-point questionnaire was used to
      evaluate the subjects theoretical knowledge of inhalation systems. The percentage
      of correct replies was used to establish reply levels. Their techniques of
      handling different systems of inhalation (pressurised cartridge, pressurised
      cartridge with spacing chamber, Turbuhaler and Accuhaler) were assessed according
      to the guidelines of the SEPAR (Spanish Society of Pneumology and Thoracic
      Surgery). 26% of the practising doctors and residents answered over 75% of the
      questionnaire correctly, with no significant differences between the two groups
      (p > 0.66). No undergraduate reached 75% of correct answers. After exclusion of
      asthmatic participants, three of the practising doctors (9.7%) and one of the
      residents (4.8%) performed the technique correctly with the four systems: there
      were no differences between the two groups (p > 0.87). No undergraduate performed
      them satisfactorily. CONCLUSIONS: Specific training for primary care doctors in
      handling inhalation therapy is recommended.

PMID- 10920522
TI  - [Psychosomatic medicine in primary care].

PMID- 10920524
TI  - [Evaluation of results in primary are: the MPAR-5 project].

PMID- 10920525
TI  - [Primary care journals in the Internet].

PMID- 10920526
TI  - [Efficacy of influenza vaccine in institutionalized patients].

PMID- 10920527
TI  - [Family physicians and continuity of care].

PMID- 10920528
TI  - [Drug anamnesis and drug adverse reactions].

PMID- 10920529
TI  - [Synthesis and structural study of substituted arylideneimidazolidines and
      arylidenebenzothiazines].
AB  - Synthesis and physico-chemical properties of six 5-arylidene-3-benzyl-1-methyl-2
      thioxoimidazolidin-4-ones and three 2-arylidene-6-nitro-2H-1,4-benzothiazin-3(4H)
      ones have been described. These new compounds were synthetised by Knoevenagel
      condensation reaction from aromatic aldehydes. The N-alkylation reaction of
      arylidenebenzothiazines by methyl iodide give the N
      methylarylidenebenzothiazines.

PMID- 10920530
TI  - New indole, aminoindole and pyranoindole derivatives with anti-inflammatory
      activity.
AB  - 6-Methoxy-1-methyl-2,3-diphenyl indol-5-carboxaldehyde (2) was demethylated to
      give the 6-hydroxy derivative (3) which was cyclized to the pyrano[3,2-f]indole
      derivatives (4a-d) by the action of ethyl acetoacetate, diethyl malonate,
      malononitrile, ethyl cyanoacetate. When 4c was boiled in acetic acid, it gave 4d.
      Reduction of 4c by sodium borohydride yielded the orthoaminonitrile (5). Friedel
      Craft's acetylation of 1b yielded the 5-acetyl derivative (6), which reacted with
      hydrazine hydrate, o-toluidine and o-aminophenol to afford (7a-c). Demethylation
      of (1b) yielded the hydroxyl derivative (8), which differs from compound (9)
      obtained by demethylation of 6-methoxy-2,3-diphenyl-indole (1a). Friedel Craft's
      acetylation of 9 gave the 7-acetyl compound (10) which yielded the hydrazone
      (11). The reaction of primary aromatic amines, (i.e. p-nitroaniline, p-anisidine
      and p-bromo aniline) with 6-methoxy-1-methyl-2,3-diphenyl-indol-5-carboxaldehyde
      (2) gave the Schiff bases (12a-c). The latter compounds were reduced by sodium
      borohydride to yield the corresponding Mannich bases (13a-c). Treatment of 12a-c
      with thioglycolic acid led to the thiazolidin-4-one-derivatives (14a-c). When
      (12a-c) reacted with cyanoacetamide, the amino group was replaced by the active
      methylene to form the cyano compound (15). The structure was confirmed by
      reacting the carboxaldehyde (2) with cyanoacetamide to yield (15).
      Pharmacological screening was has been carried out to test the anti-inflammatory
      activity, ulcerogenecity, effect on the isolated rabbit intestine and the
      antispasmodic activity.

PMID- 10920531
TI  - In vitro release and antiinflammatory activity of topical formulations of
      ketoprofen.
AB  - Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug (NSAID) widely
      used in clinical practice for the control of acute and chronic pain of soft
      tissues and skeletal muscle system. The importance of KP in the therapeutic
      field, has stimulated the development of topical dosage forms to improve its
      percutaneous absorption through the application site. Moreover they could provide
      relatively consistent drug levels for prolonged periods and avoid gastric
      irritation, typical side effect of NSAID oral administration. Since the topical
      formulation efficiency depends on vehicle characteristics, some different
      ointments, at 1% and 5% concentrations of KP, were evaluated by in vitro and in
      vivo studies. Among tested ointments, 1% Carbopol cream and 5% Carbopol gel
      showed the best fluxes of drug through regenerated cellulose membrane. The in
      vivo percutaneous absorption of KP, evaluated by carrageenan-induced paw edema in
      rats, showed a good correlation with the in vitro results about considered
      creams, but the gels in vivo activity was not in according to their in vitro
      behaviour. The extemporaneous Carbopol cream was able to produce a better edema
      inhibition than the commercial one, taken as a reference and widely utilized as a
      topical therapeutic item. About gels, the obtained results were nearly the
      maximum response considered possible for a topical antiinflammatory drug.

PMID- 10920532
TI  - Quantitative structure-activity relationship of phenoxy and benzyloxy acid
      derivatives as antisickling agents.
AB  - Quantitative structure activity relationship of Hansch-type has been applied to
      develop correlation between the calculated physicochemical properties and the in
      vitro activities of phenoxy and benzyloxyacetic acid derivatives as antisickling
      agents. The antisickling effect of these compounds was first reported by Abraham
      et al., and is used as a database of this study. QSAR for these compounds was
      generated in order to provide more information about the structure requirements
      for the design of more active antisickling analogs. The solubility ratio A/Ao for
      22 phenoxyacetic acids and 15 benzyloxyacetic acids were used to develop
      equations using hydrophobic (pi), electronic (sigma) and molar refraction (MR)
      parameters. Equations 1 and 2 with correlation coefficients of 0.872 and 0.894
      respectively, were obtained for phenoxy and benzyloxy acetic. Potencies were
      correlated positively with pi values of ortho, meta and/or para substituents.
      Positive correlations were also obtained for sigma constants of para and/or meta
      substituents. Negative correlations, on the other hand, were obtained with the MR
      values of para substituents in the benzenic ring of the benzyloxy acid series.
      Using the generated correlation equation 2, three potent antigelling
      benzyloxyacetic acid derivatives were proposed and reported. These compounds are
      expected to be very promising antisickling agents having A/A. values of 1.016,
      1.124 and 1.138.

PMID- 10920534
TI  - The essential oil composition of Thymus tosevii and Thymus macedonicus from
      Bulgaria.
AB  - Essential oils composition of Thymus tosevii Velen. and Thymus macedonicus (Deg.
      et Ur.) Ronn. from Bulgaria were examined by analytical GC and GC-MS techniques.
      39 components were separated in the oil of T. tosevii and 22 of them were
      identified, representing 94.37% of the oil. The most abundant constituents were:
      terpinyl acetate (43.59%), thymol (11.43%) and nerol (11.72%). More than 70
      components were separated in the essential oil of T. macedonicus, 35 were
      identified, representing 96.03% of the oil. The major components were geranyl
      acetate (30.00%) and terpinyl acetate (17.30%), followed by lower amounts of
      nerol (14.25%), linalool (12.94%) and thymol (4.14%). Both examined taxa
      contained essential oils composed mainly from monoterpene oxygenate compounds
      while the fractions of monoterpene hydrocarbons as well as sesquiterpene
      components were very low.

PMID- 10920533
TI  - Dissolution evaluation of marketed tetracyclines solid oral dosage forms.
AB  - Tetracyclines are produced by several pharmaceutical industries, mainly as
      capsule dosage form. This paper aimed to evaluate quality performance of
      commercially available tetracycline and oxytetracycline hydrochloride capsules
      and doxycycline hydrochloride enteric-coated tablets by means of in vitro
      dissolution test. 36 samples from 12 different producers containing 500 mg of
      tetracycline and oxytetracycline and 100 mg of doxycycline were analyzed using
      the USP XXIII procedures. Thirty four samples (94.4%) were approved and the
      remaining two samples (5.6%) were rejected. Although only one of the producers
      had some samples rejected, this fact must be seriously taken into account,
      considering the need of a highly qualified industrial production of medicines.

PMID- 10920535
TI  - Binding effectiveness of Colocassia esculenta gum in poorly compressible drugs
      paracetamol and metronidazole tablet formulations.
AB  - The effectiveness of a polysaccharide gum obtained from the cormels of Colocassia
      esculenta was evaluated comparatively with acacia and methylcellulose as binders
      in the formulation of poorly compressible drugs. The granules of these drugs
      produced by wet massing method using colocassia and acacia gums as binders have
      high compressibility index indicating poor flow. Based on this parameter, the
      granules produced with methylcellulose as binder seem to flow better. The
      properties of tablets evaluated include breaking strength, friability,
      disintegration time and dissolution rate. The new polysaccharide gum showed
      better concentration-strength profile than acacia while methylcellulose yielded
      mechanically more stable tablets than the two binders. The resistance of tablets
      to abrasion was poor in metronidazole tablets formulated with colocassia gum. The
      in vitro availability characteristics showed that tablets produced with the new
      gum show acceptable disintegration time and release profile within a certain
      range of its concentration in tablets. At 4% w/w nominal concentration of
      colocassia gum in metronidazole tablets and 6% w/w in paracetamol, tablets show
      very long disintegration time and prolonged release profile. The binders used for
      comparison yielded tablets that show better in vitro release characteristics.

PMID- 10920536
TI  - Effect of vitamin "A" on free radical cascade in pregnancy induced hypertension.
AB  - The role of vitamin A therapy in pregnancy induced hypertension (P.I.H.) on free
      radical cascade was studied in P.I.H. patients of third trimester. It was found
      that vitamin A therapy causes statistically significant decrease in lipid
      peroxidation. However it has no effect on superoxide dismutase and catalase. This
      indicates that vitamin A acts as chain breaking antioxidant. The present study
      opens a future prospective of giving vitamin A for the prophylaxis of P.I.H.

PMID- 10920537
TI  - Significance of free radicals in chronic tonsillitis.
AB  - The present study was carried on adolescents suffering from chronic tonsillitis.
      Blood (pre and post tonsillectomy) as well as tonsil samples were evaluated for 
      MDA, SOD and Catalase. Our results showed a decrease in level of MDA and increase
      in SOD and Catalase levels post tonsillectomy. Presence of MDA and SOD in
      tonsillar tissue reinforce involvement of oxidative stress in pathophysiology of
      chronic tonsillitis.

PMID- 10920538
TI  - Haemophilus influenzae type B disease control using PENTACEL, Canada, 1998-1999.

PMID- 10920539
TI  - Progress towards global poliomyelitis eradication, 1999.

PMID- 10920540
TI  - Statement on influenza vaccination for the 2000-2001 season. An Advisory
      Committee Statement (ASC). National Advisory Committee on Immunization (NACI).
AB  - The National Advisory Committee on Immunization (NACI) provides Health Canada
      with ongoing and timely medical, scientific, and public-health advice relating to
      immunization. Health Canada acknowledges that the advice and recommendations set
      out in this statement are based upon the best current available scientific
      knowledge, and is disseminating this document for information purposes. Persons
      administering or using the vaccine should also be aware of the contents of the
      relevant product monograph(s). Recommendations for use and other information set
      out herein may differ from that set out in the product monograph(s) of the
      Canadian licensed manufacturer(s) of the vaccine(s). Manufacturer(s) have only
      sought approval of the vaccine(s) and provided evidence as to its safety and
      efficacy when used in accordance with the product monographs.

PMID- 10920541
TI  - Prevention and control of neonatal sepsis.

PMID- 10920542
TI  - Individualized developmental care in the newborn intensive care unit.
AB  - With recent advances on newborn intensive care, the survival rate of very low
      birth weight preterm infants has been improved. The consequently new morbidities
      such as learning disabilities, behavioral problems, lower mean IQ and motor
      clumsiness have become more frequent. Neonatal individualized developmental care
      seeks to read the behavior of premature infants, and pace our procedures and
      caregiving according to individual infant's cues. Studies have shown that with
      implementation of developmental care, the time spent on ventilator and
      hospitalization was decreased, and infants started oral feeding earlier. The
      short and long-term neurobehavioral outcomes were improved. Developmental care
      focuses not only on changing the environment to provide a calming and soothing
      environment for the infants and family, but also provides a chance for all the
      staff members to read the behavior of the infants, think and reflect before doing
      something to the infants.

PMID- 10920543
TI  - Nosocomial infection in a neonatal intensive care unit--from a viewpoint of
      national health insurance.
AB  - In order to survey both the epidemiology of nosocomial infection in our neonatal
      intensive care unit (NICU) and the changing face of nosocomial infection after
      the introduction of National Health Insurance (NHI) in Taiwan, we retrospectively
      reviewed the nosocomial infections which occurred in our NICU from March 1, 1991,
      to February 28, 1999. We also compared the nosocomial infections from the
      viewpoint of NHI. The mean rate of nosocomial infections in our NICU during these
      8 years was 13.6%, and it had significantly increased after the NHI plan was
      implemented (from 7.9% to 19.0%). The most common type of nosocomial infection
      was blood stream infection (53.8%, 120 of 223 infections). Coagulase-negative
      Staphylococci and fungi were the two most common pathogens of nosocomial blood
      stream infection in our NICU, accounting for 28.1% and 24.2% of the infections,
      respectively. The survival rate of very low birth weight (VLBW) infants increased
      from 76.3% to 78.4% after the implementation of NHI. However, the nosocomial
      infection rate of the VLBW infants had markedly increased from 22.6% to 41.9%.
      The total number of hospitalization days of the patients with nosocomial
      infection was significantly greater than that of those without nosocomial
      infections (p < 0.05), and the patients with the lower birth weights had longer
      hospital stays. The risk factors for nosocomial infection including invasive
      procedures, multiple and empirical antibiotics, and extremely low birth weight
      premature infants, remained the same, but the prevalence of nosocomial infection
      in the neonatal intensive care unit has changed markedly since the NHI plan
      began. Further investigation to determine strategies for preventing nosocomial
      infection in very low birth weight infants is warranted.

PMID- 10920544
TI  - Relationship of serum lactate dehydrogenase, creatine kinase, aspartate
      aminotransferase concentrations and severe intraventricular
      hemorrhage/leukomalacia in very low birth body weight preterm neonates.
AB  - Estimations of serum enzyme values are widely employed as valuable diagnostic
      aids in diseases. Most commonly employed enzymes include Aspartate
      aminotransferase (AST), Lactate dehydrogenase (LDH), and Creatine kinase (CK).
      The study was designed to determine the relationship of elevated postnatal serum
      LDH, CK, and AST concentrations within the first day of life and the risk of
      suffering severe intraventricular hemorrhage (IVH) and/or periventricular
      leukomalacia (PVL) in VLBW preterm newborns. 81 preterm neonates whose birth body
      weight < 1500 gm were enrolled. Serums were obtained for measurement within the
      first postnatal day. Cranial ultrasound scans were performed twice per week after
      birth until their body weight was above 2300 gm or postconceptional age above 40
      weeks. Significant difference was noted in serum LDH and CK concentrations in
      severe IVH/PVL infants (p < 0.05). No difference was found in serum AST values.
      Compared with the cut-off values of 1933 IU/L of LDH concentration and 652 IU/L
      of CK, the predictive values revealed a sensitivity, specificity, negative
      predictive value and positive predictive value of 76.9%, 89.7%, 95.3% and 58.8%,
      respectively. In conclusion, higher serum LDH and/or CK concentrations within the
      first day of life were associated with risk for development of severe IVH/PVL.

PMID- 10920545
TI  - Arylamine N-acetyltransferase activity and 2 aminofluorene-DNA adducts formation
      in rat glial tumor cells.
AB  - Arylamine N-acetylation capacity by the N-acetyltransferase (NAT) may be an
      important causative factor in the initiation of cancer. Arylamine-DNA adducts
      formation have been correlated with the carcinogenic effect of heterocyclic
      aromatic amines. NAT activity in rat glial tumor cells was measured by high
      performance liquid chromatography (HPLC) using 2-aminofluorene (2-AF) and p
      aminobenzoic acid (PABA) as substrares. 2-AF-DNA adducts formation in rat glial
      tumor cells was investigated by gamma-[32p]-dATP and HPLC using 2-aminofluorene
      as substrates. The activities (Mean +/- SD) of NAT in rat glial cells was 1.08 +/
      0.18 nmol/min/mg protein for the acetylation of 2-aminofluorene (n = 12), and
      0.96 +/- 0.16 nmol/min/mg protein for the acetylation of p-aminobenzoic acid (n =
      12). 2-AF-DNA adducts formation in rat glial tumor cells with 30 microM and 60
      microM AF were 0.48 +/- 0.16 and 0.70 +/- 0.12 pmol/mg DNA, respectively. The
      results indicate that NAT was present in rat glial tumor cells, activating AF to
      become a metabolite able to bind covalently with DNA to form 2-AF-DNA.

PMID- 10920546
TI  - The feasibility of using photographs to estimate historical heights of children.
AB  - In studying the growth and development of children, records of body heights are
      often unavailable for certain periods of time. To evaluate the feasibility of
      using photographs to estimate body heights in the past, we obtained 23
      photographs taken within two months of a documented measurement of height from a
      cohort of an on-going study. From each photograph, an object was selected as the
      reference, and the historical height of the child was estimated by proportional
      projection according to the height of the reference. Two independent sets of
      estimates were made, and both correlated well with measured heights (correlation
      coefficient = 0.99, p < 0.0001). The mean differences between the measured and
      estimated heights were 1.4 cm and 1.5 cm respectively, and both were not
      statistically significant (Wilcoxon signed rank test, p > 0.05). The average
      differences between the two sets of estimates was only 0.1 cm (p > 0.05 for
      Wilcoxon signed rank test), which indicates a high reproducibility. Photographs
      taken in the "landscape" style tended to provide better estimates than those
      taken in the "portrait" style. Without any high technology equipment, this simple
      approach can be readily applied to obtain satisfactory estimates for
      epidemiological studies.

PMID- 10920547
TI  - Epstein-Barr virus encephalitis in children.
AB  - Fourteen children with Epstein-Barr virus (EBV) encephalitis admitted to our
      pediatric department during the period 1988 to 1998 were collected and reviewed
      to characterize the clinical, laboratory and neuroradiological findings. There
      were 7 boys and 7 girls. The age of onset ranged from 10 months to 14 years.
      Among them, 5 patients belonged to Alice in Wonderland syndrome, 5 were diagnosed
      as acute viral encephalitis, 1 presented with acute meningoencephalitis followed
      by cerebellitis, the remaining 3 cases attributed to acute disseminated
      encephalomyelitis. The main symptoms were fever (43%), seizure (36%), bizarre
      behavior (31%), headache (21%) and metamorphopsia (36%). The presenting signs
      included altered consciousness (50%), meningeal sign (14%), bulbar sign (14%),
      cerebellar sign (7%), and cranial nerve palsy (7%). Classic findings of
      infectious mononucleosis were obscure. The laboratory data showed the existence
      of atypical lymphocyte in only one case but positive serology for EBV infection
      in all patients. Pleocytosis was found in 3 (30%) of 10 patients examined. Eight
      (67%) of 12 patients had nonspecific electroencephalographic changes in the acute
      stage. Computed tomography (CT) scans were abnormal in 2 (40%) of 5 patients
      tested; while magnetic resonance image (MRI) disclosed lesions in 5 (56%) of 9
      patients, with abnormal signals in various parts of the brain. Single photon
      emission computed tomography (SPECT) brain scan showed abnormal perfusion lesions
      in 3 (75%) of 4 patients studied. The results demonstrate the diversity of
      neurological manifestations of EBV encephalitis. EBV should be considered in any
      acute neurological illness of uncertain etiology in the pediatric population.
      While MRI remains the image of choice in EBV encephalitis, SPECT detects the
      abnormal perfusion more precisely in a substantial number of patients.

PMID- 10920548
TI  - Cerebral infarction in newborns: report of two cases.
AB  - Neonates with cerebral infarction do not present with specific symptoms and the
      condition is usually insidious, so many atypical cases are not diagnosed properly
      during the neonatal stage. Normal neurological examination results may be found
      in newborns who have actually had a cerebral infarction insidiously. We present
      two newborns with cerebral infarction. One had clinical symptoms of seizures.
      Brain computed tomography showed a low-attenuated area and magnetic resonance
      angiography showed a decreased caliber and number of cerebral artery branches.
      The other had normal neurological examination results. He was referred to our
      hospital due to cyanosis. Brain sonography revealed a focal hyperechoic area and
      T2 weighted magnetic resonance image showed an increased signal intensity area.
      The incidence, etiologies, clinical and radiographic findings are also reviewed.

PMID- 10920549
TI  - Vitamin D deficiency rickets due to inappropriate feeding: report of one case.
AB  - Vitamin D deficiency rickets is rare among infants and children in the
      industrialized countries. In this paper, we report a 2-year-5-month-old girl with
      aching and bowed legs. A food allergy with atopic dermatitis was diagnosed since
      her early infancy. Strict dietary restrictions were done and she was mostly fed
      soybean juice and rice foods. Fortified soybean formula (Isomil) was introduced
      one month before admission. Vitamin D deficiency rickets was diagnosed by a
      history of inappropriate feeding, roentgenographic and laboratory findings. The
      therapeutic regimen included 1, 25-dihydroxycholecalciferol 0.5 ug/day and
      calcium carbonate 100 mg/kg/day. Extensive nutritional counseling was also given
      for correction of aberrant dietary practices. After a one-year follow-up, there
      was radiological evidence of bone healing, and marked improvement of leg
      deformities.

PMID- 10920550
TI  - Barrett's esophagus in a child with de Lange syndrome: report of one case.
AB  - Barrett's esophagus, a premalignant condition, is recognized as stratified
      squamous epithelium of the esophagus substituted by columnar epithelium. The risk
      factors for development of Barrett's esophagus include frequent gastroesophageal
      reflux, esophageal stricture, male sex and mental retardation, but there is no
      report of Barrett's esophagus in children with de Lange syndrome. We report a 7
      year-old boy who was diagnosed as de Lange syndrome shortly after birth and had
      gastroesophageal reflux since early infancy. Upper gastrointestinal endoscopic
      examination revealed a cauliflower-like mass and a pink-red velvety mass over the
      lower third of the esophagus. Biopsy showed goblet cells metaplasia, confirming
      Barrett's esophagus. We suggest surveillance of Barrett's esophagus could be done
      ahead of schedule in children with long-standing gastroesophageal reflux or with
      de Lange syndrome.

PMID- 10920551
TI  - Xanthoma of bone in a normolipidemic child: report of one case.
AB  - Xanthoma invasion of the bone is a very rare disease especially in normolipidemic
      children. Bone erosion can be found in patients with this disease. However, due
      to the similarity of the symptoms of xanthoma with many other diseases including
      malignancy, the other diseases may initially be to be suggested and xanthoma may
      not even be considered. In this paper, we present an 8-year-old normolipidemic
      male child with a parietal bone xanthoma proved using tissue diagnosis. The
      clinical, radiographic and histological findings are also reviewed.

PMID- 10920552
TI  - Describing shape changes in the human mandible using elliptical Fourier
      functions.
AB  - Elliptical Fourier functions (EFF) were generated for the boundary outline of the
      mandibular form in 24 non-orthodontic growth study subjects at 9, 11, 13, and 15
      years of age. The mean residual fit (observed versus predicted points) of the
      mandibular form was 0.11 mm, with a range from 0.09 to 0.14 mm, suggesting an
      accurate fit. The mean plot for each of the four age groups was area standardized
      and superimposed on the centroid. Shape changes in males and females were found
      to be similar. No significant shape changes were found between 9 and 11 years.
      Shape changes were observed in the lower incisor area, the mental region, the
      body of the mandible, and the gonial angle area between 11 and 15 years. These
      changes coincided with the onset of the pubertal growth spurt.

PMID- 10920553
TI  - The changes in temporomandibular joint disc position and configuration in early
      orthognathic treatment: a magnetic resonance imaging evaluation.
AB  - This study aimed to examine the effects of chin cup therapy on the
      temporomandibular joint (TMJ) disc position and configuration with magnetic
      resonance imaging (MRI). Twenty-five individuals ranging in age from 5 to 11
      years were evaluated. The treatment group consisted of 15 subjects (10 females
      and five males) with prognathic facial structures, while the control group
      comprised 10 subjects (six females and four males) with an orthognathic facial
      structure. The magnitude of the chin cup force applied to the mandible was 600 g.
      Unilateral MRIs of the TMJ were taken in all subjects at the beginning and end of
      the study. No statistically significant changes in the TMJ disc position and
      configuration during the treatment and control periods could be seen. The values
      of the alpha angle measurements were found to be different in the treatment and
      control groups at the beginning (166.23 +/- 2.15 and 172 +/- 1.97, respectively),
      and end of the treatment and control periods (160.00 +/- 2.16 and 172.00 +/-
      2.68). These findings show that if the chin cup appliance is used at an early age
      and with appropriate forces, there will be no adverse effect on the TMJ disc
      position and configuration.

PMID- 10920554
TI  - Safe orthodontic bonding for children with disabilities during general
      anaesthesia.
AB  - General anaesthesia (GA) may be employed to overcome management difficulties in
      the orthodontic treatment of disabled children. This report introduces the
      application of a rubber dam as a useful aid for a high quality bonding and as an
      effective safeguard in bonding of brackets in general anaesthesia, in the
      handicapped in particular. GA was used in 12 patients, of a cohort of 49 disabled
      patients, to facilitate the placing of the fixed appliance. The first seven were
      bonded solely with the use of an oropharyngeal pack and a high velocity suction
      to prevent aspiration, and the last five additionally underwent placement of a
      rubber dam. The use of a rubber dam to facilitate the safe and reliable bonding
      of orthodontic brackets in handicapped children under general anaesthesia is
      highly recommended.

PMID- 10920555
TI  - Change in the width of the mandibular body from 6 to 23 years of age: an implant
      study.
AB  - After the ossification of the mandibular symphysis, shortly after birth, changes
      in mandibular width would be expected to occur only by surface apposition or
      resorption on the buccal surfaces of the left and right mandibular halves.
      However, evidence for an opening hinge movement of the two mandibular halves
      around a vertical axis located in the region of the mandibular symphysis was
      recently found in longitudinal studies of 29 subjects with unilateral implant
      markers in the mandible. These subjects were followed from 8.5 to 15.5 years of
      age (Korn and Baumrind, 1990; Baumrind and Korn, 1992). The aim of the present
      investigation was to examine whether the presence of such an age-related increase
      in mandibular body width could be confirmed in a sample with bilateral implant
      markers in the mandible. The sample comprised 10 subjects (3F, 7M) from the files
      of another longitudinal study with implant markers (Bjork, 1968). A total of 122
      pairs of annual lateral and postero-anterior (p-a) cephalometric records were
      available, covering longitudinal observation periods ranging from 8 to 16 years
      within an age interval of between 6 and 23 years. The width between a right and
      left side mandibular implant marker was measured with digital callipers on all p
      a radiographs. Each measurement was corrected mathematically for various sources
      of radiographic enlargement. A small, but statistically significant increase in
      the distance between the right and left implant markers, i.e. in the bilateral
      width of the mandibular body, was observed in all subjects. The total increase in
      width in each subject ranged from 0.7 to 1.7 mm for the various periods of
      observation (P < or = 0.01). For the 12-year period from 6 to 18 years, the
      average total increase was 1.6 mm (P < or = 0.001, SD = 0.42), i.e. 0.13 mm/year.
      After this age there was no systematic trend. The mechanism for this increase in
      width is unknown. It is suggested that during postnatal growth, an increasing
      load from the masticatory occlusal forces might influence endosteal bone
      remodelling in the mandibular body, thus producing or allowing a gradual
      permanent outward bending of the right and left mandibular halves.

PMID- 10920556
TI  - Persistence of deciduous molars in subjects with agenesis of the second
      premolars.
AB  - The purpose of the present study was to investigate persistent primary second
      molars in a group of young people in their late twenties with agenesis of one or
      two second premolars. In 1982-83 it was decided, in connection with the
      orthodontic evaluation of 25 patients, to allow 35 primary molars (one or two in
      each patient) to remain in situ. All patients had mixed dentitions and agenesis
      of one or two premolars. The primary teeth were generally in good condition,
      although root resorption and infra-occlusion (compensated by occlusal composite
      onlays) occurred. In 1997, 18 of the 25 patients with a total of 26 retained
      primary molars were reexamined, comprising a clinical examination for
      exfoliation, extraction, loosening, and ankylosis, and a radiographic examination
      for root resorption, tooth morphology (crown and root), and alveolar bone
      contour. The examination showed that the degree of root resorption was unaltered
      in 20 of the 26 primary molars. In the permanent dentitions, where these primary
      molars persisted, there were no morphological deviations. Three of the six
      remaining primary molars had been extracted and three showed extensive
      resorption. In three of the 26 primary molars the infra-occlusion had worsened.
      The present study shows that persistence of primary second molars in subjects
      with agenesis of one or two premolars, and normal morphology of the permanent
      dentition can be an acceptable, semi-permanent solution for the patient. Whether
      this could also be an acceptable long-term solution will be shown by follow-up
      studies.

PMID- 10920557
TI  - The long-term survival of lower second primary molars in subjects with agenesis
      of the premolars.
AB  - This study investigated 41 subjects, 13 male and 28 female, with agenesis of one
      or both lower second premolars, and with retained lower second primary molars.
      Intra-oral radiographs of 59 primary teeth were examined to judge the resorption
      of the mesial and distal roots, and were measured to record infra-occlusion of
      the primary teeth and tipping of the adjacent permanent teeth. The study
      commenced at 11-12 years of age. The mean age at the last measurement was 20
      years 6 months (SD 3.62, range 13.6-31.8 years). During the observation period,
      only two of the 59 primary teeth were exfoliated. Five were extracted, two of
      which were replaced by upper third molar transplants. Beyond the age of 20 years
      no teeth were lost. Root resorption varied widely between individuals, but was
      slow. There was no typical pattern for development of infra-occlusion. Mean infra
      occlusion was 0.47 mm (SD 1.13) at 11-12 years, increasing by less than 1.0 to
      1.43 mm (SD 1.13) at age 17-18 years. At age 19-20 years, 55 per cent of teeth
      showed infra-occlusion between 0.5 and 4.5 mm, but 45 per cent showed no infra
      occlusion. The space between the first molar and first premolar was a mean of
      10.35 mm (SD 0.76) at age 10-12 years compared with the mean width of the second
      primary molar of 10.53 mm (SD 0.51). The space reduced by less than 0.5 mm to
      9.95 mm (SD 1.50) at age 17-18 years. If primary molars are present at 20 years
      of age they appear to have a good prognosis for long-term survival.

PMID- 10920558
TI  - Statistical methods for the comparison of measurements derived from orthodontic
      imaging.
AB  - Biometric comparison procedures for dental imaging methods with continuous
      outcome were reviewed, mainly concentrating on assessment and comparison of
      accuracy and precision according to the study design. Univariate graphical and
      numerical representations of corresponding deviations were summarized to derive a
      'check list' of minimum information necessary to compare the measurement methods.
      The methods reviewed in this investigation are illustrated by the comparison of
      conventional (radiographic) cephalometry versus assessment using the DigiGraph in
      50 female children. A paired t-test and the corresponding confidence interval
      approach were used to assess deviations in location of two imaging methods; the
      test procedures of Maloney/Rastogi, Hahn/Nelson, and Grubbs were surveyed as
      proposals for the comparison of precisions in paired data. The Krippendorff
      coefficient was used as an aggregate measure for method concordance. Since these
      methods can be performed by simple modification of standard options available in
      most statistical software packages, this review intends to enable dental
      researchers to choose the correct methods, and perform adequate data analysis and
      representation.

PMID- 10920559
TI  - Signs of temporomandibular disorders in girls receiving orthodontic treatment. A
      prospective and longitudinal comparison with untreated Class II malocclusions and
      normal occlusion subjects.
AB  - The aim of this investigation was to prospectively and longitudinally study signs
      of temporomandibular disorders (TMD) and occlusal changes in girls with Class II
      malocclusion receiving orthodontic treatment and to compare them with subjects
      with untreated Class II malocclusions and with normal occlusion subjects. Three
      groups of age-matched adolescent girls were examined for clinical signs of TMD
      and re-examined 2 years later. Sixty-five Class II subjects received orthodontic
      fixed straight-wire appliance treatment (Orthodontic group), 58 subjects were
      orthodontically untreated (Class II group), and 60 subjects had a normal
      occlusion (Normal group). In the Orthodontic group, the prevalence of muscular
      signs of TMD was significantly less common post-treatment. The Class II and the
      Normal groups showed minor changes during the 2-year period. Temporomandibular
      joint clicking increased in all three groups over the 2 years, but was less
      common in the Normal group. The Normal group also had a lower overall prevalence
      of signs of TMD than the Orthodontic and the Class II groups at both
      registrations. Functional occlusal interferences decreased in the Orthodontic
      group, but remained the same in the other groups over the 2 years. In conclusion,
      orthodontic treatment did not increase the risk for or worsen pretreatment signs
      of TMD. On the contrary, subjects with Class II malocclusions and signs of TMD of
      muscular origin seemed to benefit functionally from orthodontic treatment in a 2
      year perspective. The Normal group had a lower prevalence of signs of TMD than
      the Orthodontic and the untreated Class II groups.

PMID- 10920560
TI  - Temporomandibular disorders and the need for stomatognathic treatment in
      orthodontically treated and untreated girls.
AB  - The aim of this investigation was to study symptoms of temporomandibular
      disorders (TMD) and headaches longitudinally in girls with Class II malocclusions
      receiving orthodontic treatment in comparison with subjects with untreated Class
      II malocclusions and girls with normal occlusion, and to evaluate the need and
      demand for stomatognathic treatment. The frequency and location of subjective
      symptoms of TMD and headaches were registered by means of an interview and a
      questionnaire in three groups of age-matched adolescent girls. Sixty-five Class
      II subjects received orthodontic fixed straight-wire appliance treatment
      (Orthodontic group), 58 with Class I malocclusion were orthodontically untreated
      (Class II group) and 60 had a normal occlusion (Normal group). Individual
      fluctuations of reported symptoms of TMD were found in all three groups over the
      2-year period of the study. Subjects with untreated Class II malocclusions rated
      their overall symptoms of TMD as more severe than the Orthodontic and the Normal
      groups. In the Orthodontic group, the prevalence of symptoms of TMD decreased
      over the 2 years. The overall prevalence of symptoms of TMD was, however, lower
      in the Normal group than in the other two groups. The need for stomatognathic
      treatment in the whole sample was estimated to be 13 per cent, while the actual
      demand was 3 per cent. The large fluctuation of symptoms of TMD over time leads
      us to suggest a conservative treatment approach when stomatognathic treatment in
      children and adolescents is considered. The results show that orthodontic
      treatment did not increase the risk of TMD.

PMID- 10920562
TI  - A new method of measuring how much anterior tooth alignment means to adolescents.
AB  - The aim of this study was to develop an instrument to measure an individual's
      value of the appearance of their anterior teeth. Structured interviews were
      carried out using the Index of Orthodontic Treatment Need (IOTN) as a basis for
      time trade-off and visual analogue utility measurement. The subjects of the study
      were forty-five 11-14-year-old children at new patient consultation with an
      orthodontist (seekers) and forty-five 11-14-year-old children in school (non
      seekers) It was possible to derive utility values using the techniques adopted.
      The seekers and non-seekers of treatment had significantly different utility
      values for anterior tooth appearance (P < 0.05, Mann-Whitney). This study
      suggests that it is possible to develop utilities that reflect how patients value
      the appearance of anterior teeth. These utilities had a predictive validity in
      that there were significant differences in seekers' and non-seekers' utility
      values. The seekers placed a higher value than non-seekers on the desirability of
      a good aesthetic appearance.

PMID- 10920561
TI  - Effects of a three-dimensional bimetric maxillary distalizing arch.
AB  - This study aimed to investigate the dental effects of a three-dimensional (3D)
      bimetric maxillary distalizing arch. The Wilson rapid molar distalization
      appliance for Class II molar correction was used in 14 patients (10 girls and
      four boys with a mean age of 12.18 years). The open coil springs were activated
      with bent Omega stops and Class II intermaxillary elastics. The mandibular
      anchorage was gained by a 0.016 x 0.016 utility arch with a 3D lingual arch or a
      lip bumper with a standard lingual arch. The lateral cephalograms taken before
      and after treatment formed the material of the research. A Wilcoxon test was used
      to statistically evaluate the treatment effects. The results showed that the
      distal tipping of the maxillary first and second molars, and first and second
      premolars and canines were statistically significant. Significant distal movement
      occurred in all posterior and canine teeth. The maxillary first molar
      distalization was found to be 3.5 mm. The maxillary incisor showed significant
      proclination and protrusion. The decrease in overbite was found to be
      statistically significant. The mandibular plane angle significantly increased by
      a mean of 0.5 mm. In addition, significant soft tissue changes were observed.

PMID- 10920563
TI  - Functional and social discomfort during orthodontic treatment--effects on
      compliance and prediction of patients' adaptation by personality variables.
AB  - During the course of treatment orthodontic patients frequently endure a number of
      functional complaints and are anxious about their appearance. The aims of this
      longitudinal study were to follow the progress of patients' adaptation to
      discomfort, to elucidate the putative relationship between the type of appliance
      worn and functional and social discomfort experienced, to study potential
      predictability by their attitude to treatment and to evaluate the effects of
      discomfort as predictors of patients' compliance. Eighty-four patients undergoing
      either removable, functional, or fixed appliance treatment monitored their
      complaints during the first 7 days of treatment and rated them retrospectively 14
      days, and 3 and 6 months after appliance insertion. The most frequent complaints
      were impaired speech, impaired swallowing, feeling of oral constraint and lack of
      confidence in public. A significant reduction in the number of complaints was
      observed between 2 and 7 days after insertion of the appliance. No further
      differences were revealed after longer periods of appliance wear. The type of
      appliance had an effect on impaired speech and swallowing. Patients' expectations
      of favourable treatment performance and appreciation of dental aesthetics were
      predictive of reported feeling of oral constraint and lack of confidence in
      public. There was a relationship between the complaints and acceptance of the
      appliance, as well as between lack of confidence in public and compliance with
      treatment. The results of this study highlight the importance of patients'
      attitudes to treatment and of functional and social discomfort associated with
      appliance wear for the theory and practice of the management of orthodontic
      patients, and the necessity for early intervention by clinicians.

PMID- 10920565
TI  - The force levels required to mechanically debond ceramic brackets: an in vitro
      comparative study.
AB  - The in vitro force levels generated by four differing methods of mechanical
      debonding techniques for ceramic brackets, using debonding pliers, were measured.
      The forces generated using wide (method W) and narrow blades (method N) were
      compared with those generated using a diagonally opposite corner application of
      the wide blades (method C) and incisal-gingival application of a pair of pointed
      blades (method P). Chemically retained ceramic brackets (Transcend) were bonded
      to bovine teeth using a filled, two-paste, chemically cured composite (Concise).
      After 24 hours storage at 37 degrees C in water, each specimen was subjected to
      one of the four mechanical debonding methods in a custom-built jig, simulating
      the clinical application of conventional debonding pliers. A one-way ANOVA with a
      Tukey's honestly significant difference test revealed statistically significant
      differences in debonding strengths between the four methods at the 0.05 level of
      significance. The mean debonding strength generated by method C was 40 and 25 per
      cent lower than that for methods W and N, respectively. Scoring of the adhesive
      remnant index (ARI) revealed that the predominant bond failure site was at the
      bracket/adhesive interface for all groups. Macroscopically, no enamel damage or
      bracket fractures were observed.

PMID- 10920564
TI  - Surface characterization of retrieved NiTi orthodontic archwires.
AB  - The structure and morphological condition of retrieved NiTi orthodontic archwires
      was evaluated and any possible alterations in the surface composition of the
      alloy following 1-6 months in vivo were characterized. NiTi wires (GAC, German
      Orthodontics, ORMCO) of various cross-sections were collected through a retrieval
      protocol and were subjected to multi-technique characterization. Optical
      microscopy revealed islands of amorphous precipitants and accumulated
      microcrystalline particles. Micro MIR-FTIR investigation of the retrieved samples
      demonstrated the presence of a proteinaceous biofilm, the organic constituents of
      which were mainly amide, alcohol, and carbonate. Scanning electron microscope and
      X-ray microanalysis showed that the elemental species precipitated on the
      material surface were Na, K, Cl, Ca, and P, forming NaCl, KCl, and Ca-P
      precipitates. Increased intra-oral exposure was consistently associated with the
      presence of a mature film, while evidence of alloy delamination, pitting, and
      crevice corrosion, as well as a notable reduction in the alloy grain size was
      observed. Intra-oral exposure of NiTi wires alters the topography and structure
      of the alloy surface through surface attack in the form of pitting or crevice
      corrosion or formation of integuments. Further in vivo research is required to
      resolve the implications of the described ageing pattern in the corrosion
      resistance of the alloy, the potential for nickel leaching, as well as bracket
      archwire friction variants.

PMID- 10920566
TI  - A comparison of health state utilities for dentofacial deformity as derived from
      patients and members of the general public.
AB  - The cost-utility approach is a method of economic evaluation, which assigns a
      ratio of cost to benefit, based on utility values of the health state in
      question. It allows efficient use of health care resources and is a useful method
      in that it permits comparison of a wide range of medical interventions, including
      those which are life saving and those that improve quality of life. This study
      obtained utility values for dentofacial deformity from orthognathic patients and
      members of the general public using three recognized methods--rating scale (RS),
      standard gamble (SG), and time trade-off (TTO). There were no significant
      differences between the utility values for the two groups of respondents. Method
      agreement between the TTO and the SG (the 'gold standard') was better than that
      between the RS and SG. In addition, the SG and TTO were found to have greater
      repeatability than the RS.

PMID- 10920567
TI  - [Experiencing violence in childhood--risks and health sequelae].
AB  - OBJECTIVES: Descriptive study on health outcomes, co-morbidity, severity and
      social context in child abuse and neglect. METHODS: Cross-sectional study of
      consecutively incoming cases in eleven German Child Protection Centres between
      January and July 1997 using a standardised survey instrument. RESULTS: We report
      on 263 children from 251 families. The majority of children was less than ten
      years old, 63% were girls, 37% boys. Of all children, 134 had suffered sexual
      abuse with physical contact, 20 sexual abuse without contact, 77 physical abuse,
      62 emotional abuse and 99 neglect (multiple responses were allowed). The overlap
      between various types of abuse was considerable: many children had suffered more
      than one, a quarter more than two types of abuse. The majority of cases was
      classified as either severe and/or chronic. Most children and youngsters suffered
      emotional distress or posttraumatic stress, long-term consequences of physical
      injuries were less common. Intra-familiar relationship problems and emotional
      distress of the care-giver had greater impact on the risk for abuse or neglect
      compared to socioeconomic risk factors. In 55% child protection workers
      documented a disability in social and emotional development, in a quarter of
      children developmental retardation. CONCLUSIONS: The current, exclusive
      classification of types of abuse and neglect does not adequately describe the
      complexity of childrens' experiences of intra-familiar violence. Future research
      should be oriented towards the physical, emotional and social consequences of
      child maltreatment and use multifactorial designs to capture the complex
      aetiology and multiple acts and omissions responsible for the distress and
      injuries. Prospective studies are important to assess specific effects of child
      abuse and neglect on child development.

PMID- 10920568
TI  - [Immunization monitoring of students starting school: a regional contribution
      from the Bavaria district].
AB  - The aim of these sectional studies was to find out current mass immunisation
      rates of school beginners. The study was carried out in the administrative
      district of Dingolfing-Landau in 1999, also to examine to what extent the
      recommendations to the STIKO (Established Immunisation Committee at the Robert
      Koch-Institute) for the corresponding age-group had been complied with. To this
      end, the vaccination documents submitted at the medical examination were
      inspected, the given data recorded in a standardised way and subsequently
      rendered anonymous. According to the available results the mass immunisation
      rates for diptheria, tetanus and polio met the infection epidemiology
      requirements by over 90%. The HiB, MMR and whooping cough vaccinations were in on
      the average 80% for mass immunisation, which no longer meets the epidemiological
      requirements. BCG inoculation was only given to every tenth child in the relevant
      age group. A positive aspect was the comparatively high immunisation rate of
      almost 50% on hepatitis B immunisation. Only one child in twenty in the relevant
      age group had the full immunisation protection recommended by STIKO. Due to the
      great acceptance and willingness to co-operate on the part of the parents/legal
      guardians the review of the immunisation status through the Childrens and Young
      People's Public Health Authority (KJGD) made it possible to establish the current
      mass immunisation rate for children of one birth year. In this way, it will be
      possible by means of relevant immunisation recommendations and immunisation
      strategies to close the immunisation gaps and raise the mass immunisation rates.

PMID- 10920569
TI  - [Incidence of neurodermatitis (atopic dermatitis) in students starting school in
      Ostalbkreis in Baden-Wurttemberg].
AB  - The prevalence of atopic eczematous dermatitis differs considerably between
      countries. In a former study with preschool children the prevalence in Baden
      Wurttemberg according to data from parent questionnaires was about 10 per cent.
      Taking into account the expected false positives and false negatives led to the
      approximated unbiased prevalence of 7 to 8 percent. To evaluate this estimate,
      the Health Department Ostalbkreis used the same questionnaire in a second study
      of the same age group. The questionnaires were self-administered by the parents
      during the medical examination before school entrance. The parents of positive
      administered cases (11.2 per cent) were asked for permission to contact the
      family doctor to have the diagnosis confirmed (or not). 75 per cent of the
      positive identified cases by questionnaires were confirmed by family doctors.
      Therefore, the prevalence of atopic eczematous dermatitis in preschool children
      aged six to seven years in the area of Ostalbkreis is about 8.5 per cent.

PMID- 10920570
TI  - [Quality control in ambulatory health care. Results of an area-wide study by the
      public medical service of the Baden-Wurttemberg health insurance].
AB  - Discussions surrounding the quality of nursing care, fueled by recurring press
      reports, prompted the State Nursing Insurance Associations in Baden-Wuerttemberg
      to request the Health Insurance Medical Service to perform a quality control of
      outpatient nursing care services in the state. Based on a coordinated concept and
      for the first time in the Federal Republic of Germany, all authorized ambulatory
      institutions area-wide were subjected to a uniform assessment (total survey)
      during an official inquiry time period. The end results of these controls failed
      to verify the judgement often propagated by the press based on individual cases
      that high-quality nursing care can no longer be afforded under the present
      circumstances. On the average, 55% of the personnel provided to patients by
      outpatient nursing services were health care professionals. What is more, this
      professional staff rendered 75% of all nursing care services. The evaluation of
      the accompanied medical visits indicated that the vast majority attempted to take
      active nursing care into account. With regard to quality assurance, a great
      optimisation potential was indicated primarily in the area of nursing
      documentation. Only in about 35% of the nursing documents inspected was the
      nursing procedure always clearly evident. A future problem could arise from the
      fact that of all nursing professionals with leadership responsibilities, at the
      time of the survey only about 37% had completed the requisite professional
      training qualification programme of 460 training hours. If the time before the
      interim deadline (March 31, 2002) is not utilised, the institutions in question
      could face consequences that could threaten their very existence. It is evident
      that a large number of outpatient nursing care services in the state of Baden
      Wuerttemberg do not have their economic foundation in the domain of the Nursing
      Care Insurance Law, which affects both patient structure and care intensity. As a
      consequence, there is no quality control or inspection whatsoever for the
      majority of nursing care services rendered by ambulatory nursing care services at
      present because they are not under the jurisdiction of the German Federal Social
      Legislation SGB XI.

PMID- 10920571
TI  - [Does health status improve after re-assumption of ABM employment?].
AB  - Due to structural problems of the East German economy the level of unemployment
      will probably remain high for the next ten years. Thus, thousands of health
      employment-schemes are established to reduce negative social and financial
      consequences of unemployment for those groups that are most affected. In this
      study the effects of temporary re-employment on health within the bounds of a job
      creating measure are examined. By questionnaire employees of two firms in
      Magdeburg that exclusively occupies former unemployed men and women were asked
      about their subjective health status and changes in health status since re
      employment. 217 employees filled the questionnaire (response rate: 50%; mean age:
      45 years, mean duration of former unemployment: 18 months). About one half of the
      employees (48%) report positive effects on health after re-employment. This
      percentage is highest in the age group 50 years and older. The frequency of
      health impairments remained unchanged for half of the workers, the rest mainly
      stated fewer impairments. Poor working conditions or physical overtaxing
      decreases the positive effects of re-employment. Employees who had a positive
      attitude towards their work report on positive effects on health and other
      aspects of life more than average. CONCLUSIONS: Negative consequences of
      unemployment on physical and psychological health are well understood. On the
      other hand, our study demonstrates positive effects on health and a reduction of
      health impairments by temporary job-creating measures. This is influenced by the
      working conditions and the social environment of the employees. Further
      investigation are needed for detailed medical evaluation of job-creating schemes.

PMID- 10920572
TI  - [Psychosocial, economic and physical status of former leprosy patients in
      Uganda].
AB  - This study investigates the general living condition, the psychosocial,
      economical and physical situation of 161 leprosy patients previously treated at
      the St. Francis Leprosy Hospital at Buluba/Uganda, basing on interviews and
      clinical examinations. The results point to a negative correlation between
      general education and specific knowledge of leprosy and highlight a serious
      psychosocial situation of previously treated leprosy patients. The most important
      conclusion is that besides leprosy-specific chemotherapy, lifelong extensive
      general and leprosy-specific health education and posttreatment care can prevent
      disabilities in leprosy patients.

PMID- 10920573
TI  - [Implementation of a quality management system for the curriculum in emergency
      medicine education].
AB  - Medical teaching, training and education in basic and advanced life support were
      improved by basic quality management procedures. 3rd year medical students (n =
      276) of two consequent semesters were questionnaired about their acute emergency
      medicine curriculum. While Group A (n = 134) received a standard course, the new
      course for group B (n = 142) was reorganised on the basis of the results of group
      A. Interventive educational measures were an increased number of models provided
      for exercising the students skills, and an extension of megacode training
      possibilities. Participation of students in course design improved the overall
      performance in respect of knowledge, skills and decision-making (p < 0.05).
      Curriculum acceptance and intrinsic motivation of students however were not
      positively influenced by practical training compared to traditional knowledge
      transfer.

PMID- 10920574
TI  - [Public health codes in nursing homes for the aged].
AB  - In nursing homes for the aged and hospitals the hygienic requirements should be
      formally identical. There are considerable differences in actual practice. The
      reasons for these differences are analysed below. Concrete ways of solution can
      be based on a variety of different reasons, which make it probable that sensible
      improvements of hygienic conditions in long-term nursing and nursing for the aged
      can be attained. Of special significance are the medical officers inspections and
      official education means to create representatives in hygienic nursing care for
      the aged.

PMID- 10920575
TI  - Subjective sensation of heaviness in gout patients.
AB  - The main objective of the treatment of gout is to protect the major organs.
      Almost all gout patients require medication throughout their lives. Gout patients
      are asymptomatic during intercritical periods, even if they are not receiving
      antihyperuricemic drugs. Some patients, therefore, misinterpret that their gout
      is cured and may cease taking medication of their own accord. Thirty-two gout
      patients who had received continuous treatment with antihyperuricemic drugs for
      more than 3 months were selected. The sensation of heaviness was relieved by
      antihyperuricemic drugs in 14 (44%) of 32 patients. The heaviness did not exist
      or change in the other patients. Benzbromarone, probenecid, and allopurinol were
      found to be effective. The sensation of heaviness occurred after increased
      physical activity in 10 of 14 patients. Of 14 patients, 12 did not notice that
      the sensation of heaviness was relieved by antihyperuricemic drugs. Two
      hypotheses for the cause of heaviness are considered. One is mild gouty
      neuropathy, the other low-grade inflammation. A proper understanding that this
      symptom is relieved by antihyperuricemic drugs may serve as additional motivation
      for gout patients to take their medication regularly.

PMID- 10920576
TI  - Effects of pranlukast, a cysteinyl leukotriene antagonist, on bronchial
      responsiveness to methacholine in aspirin-intolerant asthmatics treated with
      corticosteroids.
AB  - Cysteinyl leukotrienes (cysLTs) are considered to be the most important mediator
      involved in the pathogenesis of aspirin-intolerant asthma (AIA). However, the
      role of cysLTs in the baseline condition of the pathophysiology of AIA when not
      exposed to non-steroidal antiinflammatory drugs (NSAIDs) as well as that in the
      pathophysiology of aspirin-tolerant asthma remains to be elucidated. Therefore,
      we evaluated the effect of pranlukast, a potent, selective cysLT receptor
      antagonist, on bronchial responsiveness to methacholine, a non-specific stimulus,
      in 7 well-controlled aspirin-intolerant asthmatics receiving oral or inhaled
      corticosteroid treatment. Pranlukast was orally administered at a dose of 225 mg
      twice daily to all patients for 4 weeks, and the methacholine challenge test was
      performed before and after pranlukast treatment. The methacholine provocative
      concentration producing a 20% fall in forced expiratory volume in 1 second (PC20
      FEV1) was calculated as an index of bronchial hyperresponsiveness (BHR). The
      geometric mean values of PC20-FEV1 significantly (p = 0.028) increased from 0.34
      mg/dl to 0.61 mg/dl after pranlukast treatment. No significant differences were
      observed in the baseline values of forced vital capacity (FVC) or FEV1 before and
      after pranlukast treatment. These findings suggest that antagonism of endogenous
      cysLT by pranlukast may be responsible for the improvement of BHR to
      methacholine.

PMID- 10920577
TI  - Evaluation of p53 gene mutation and loss of heterozygosity of 3p, 9p and 17p in
      precancerous lesions of 29 lung cancer patients.
AB  - To assess the multiple steps involved in carcinogenesis we evaluated p53 gene
      mutation frequencies, and loss of heterozygosity (LOH) of chromosomes 3p, 9p and
      17p in hyperplasia, squamous metaplasia, dysplasia, squamous cell carcinoma in
      situ and early squamous cell carcinoma of the bronchial epithelium, using
      immunohistochemical, polymerase chain reaction-single strand conformational
      polymorphism (PCR-SSCP) and microsatellite analysis. Overexpression of p53
      oncoprotein was observed in 31% of mild dysplasia, 50% of moderate and 67% of
      severe dysplasia. Mutation of the p53 gene, however, was confirmed only in 2
      severe dysplasias. LOH of 3p, 9p and 17p were detected in 8% of mild and 6% of
      moderate dysplasias. Among other types of bronchial lesions, two columnar cell
      hyperplasias showed LOH of 3p and 17p, respectively. These results suggest that
      LOH of 3p or 9p may be a rare but early event in the development of squamous cell
      carcinoma of the lung. In particular, deletion of 3p21.3 is a relatively common
      event in premalignancy. The results also suggest that p53 gene abnormalities
      occur during the following stage of carcinogenesis.

PMID- 10920578
TI  - Study on eight patients with malignant tumors after renal transplantation.
AB  - The high incidence of cancer after renal transplantation is now a critical
      concern since the graft survival rate has been improved extensively. We
      experienced 9 malignancies in 8 patients out of 168 recipients up to December 31,
      1999 in our hospital, consisting of a case of gastric plasmacytoma and cases of
      cancer in the liver (2), thyroid (2), prostate (1), breast (1), sigmoid colon (1)
      and gall-bladder (1). Two patients were diagnosed as having tumors within 3
      months after transplantation, suggesting post-transplant acceleration of growth
      of the latent tumors. The other patients were diagnosed at an average of 128
      months, ranging from 84 to 263 months after transplant. Two patients died of
      gastro-intestinal bleeding and acute heart failure. Four patients died directly
      of progressive neoplasm within 3 months after diagnosis. These results suggest
      that the course of malignancies developing in post-transplant recipients is more
      aggressive than that expected in non-transplant patients, and it is very
      important to intensively follow long-term surviving cases to detect the malignant
      tumors as early as possible.

PMID- 10920579
TI  - Invasive bladder cancer after cyclophosphamide administration for nephrotic
      syndrome--a case report.
AB  - We report a case of invasive bladder cancer after cyclophosphamide administration
      for nephrotic syndrome, and briefly discuss the association of bladder cancer and
      cyclophosphamide. A 6-year-old boy, who was diagnosed as having nephrotic
      syndrome, was treated with oral administration of prednisolone and
      cyclophosphamide for 4 years, receiving a total dose of 49.5 g cyclophosphamide.
      At age 27, a gross hematuria with bloody clots appeared and he presented with
      postrenal renal failure. He underwent a radical cystourethrectomy and ileal
      conduit for stage a pT3a pN0 M0 transitional cell carcinoma of the bladder. He
      was not given any adjuvant treatments because of his renal insufficiency, and he
      died from the disease 14 months after radical surgery.

PMID- 10920580
TI  - Detection of mycobacterial DNA in cervical granulomatous lymphadenopathy from
      formalin-fixed, paraffin-embedded tissue by PCR.
AB  - Cervical tuberculous lymphadenitis is the most common form of inflammatory neck
      mass in Korea. The diagnosis of tuberculosis requires proof of the presence of
      Mycobacterium tuberculosis by acid-fast staining or bacterial growth in culture.
      However, these are often difficult in cervical tuberculous lymphadenitis. The aim
      of this study was to investigate the value of the polymerase chain reaction (PCR)
      technique for detection of mycobacteria in routinely processed tissue sections of
      cervical granulomatous lymphadenopathy. In this retrospective study, twenty
      formalin-fixed, paraffin-embedded biopsy specimens from clinically and/or
      histopathologically diagnosed cervical granulomatous lymphadenopathy were
      analyzed for mycobacterial DNA by PCR. Two different primers to amplify
      mycobacterial-common 383-base pair (bp) DNA and Mycobacterium tuberculosis
      complex-specific 123-bp DNA were used. Positive PCR products were sequenced
      directly. Mycobacterial-common DNA (383-bp positive) was found in 10 of the 20
      cases. Among them, 7 cases were PCR positive with both primer sets. These seven
      cases can be considered as tuberculosis. The other three cases indicated possible
      atypical mycobacteriosis. PCR is a useful technique for the demonstration of
      mycobacterial DNA fragments in patients with clinically suspected cervical
      tuberculous lymphadenitis who have acid fast-negative histology and/or
      unsuccessful mycobacterial cultures.

PMID- 10920581
TI  - Photosensitivity in HIV-infected individuals.
AB  - OBJECTIVE: To characterize photosensitivity in HIV-infected individuals using
      minimal erythema dosage (MED) UVA (ultraviolet A light) and UVB (ultraviolet B
      light) photoprovocation light testing. DESIGN: Prospective, controlled analytical
      study. SETTING: University of California, San Francisco, between March 1995 and
      January 1997. PATIENTS: 13 HIV-seropositive patients with clinical and
      pathological features consistent with photodermatitis, 13 HIV-seropositive
      patients with biopsy-proven eosinophilic foliculitis (EF), and 10 HIV
      seropositive patients with CD4 (T helper cell) count below 200 cells/uL and no
      history of photosensitivity or EF. INTERVENTION: Each patient underwent MED
      testing for UVB. All 13 patients with suspected photodermatitis underwent full
      photochallenge testing with UVA and UVB for up to 10 consecutive week days.
      RESULTS: Mean MED to UVB in patients with clinical photosensitivity and EF was
      lower (p = 0.004 and p = 0.022 respectively) than that of patients without a
      clinical history of photodermatitis. There were no significant differences in
      mean CD4 count or Fitzpatrick skin type. Positive photochallenge tests (papular
      changes at site of provocative light testing) to UVB (9 of 13 patients) were much
      more common than reactions to UVA (3 of 13 patients) in the photodermatitis
      group. All patients with clinically active photodermatitis developed papular
      changes at the site of UVB photochallenge testing, but only 1 of 5 patients with
      photodermatitis in remission developed papular changes with UVB photochallenge
      testing. Seven of the 13 patients with photodermatitis had Native American
      ancestry. Photosensitive patients were commonly taking trimethoprim
      sulfamethoxazole (TMP-SMX), but no more commonly than EF or control patients.
      CONCLUSIONS: Photosensitivity in HIV-infected individuals appears to be a
      manifestation of advanced disease. Most patients are sensitive to UVB. The most
      severely affected individuals are both UVB and UVA sensitive, and may show
      reactions to visible light. A significant Native American ancestry may be a risk
      factor for development of photodermatitis in patients with advanced HIV disease.
      Finally, patients with eosinophilic folliculitis may be subclinically
      photosensitive.

PMID- 10920582
TI  - Expression of 27 KD, 65 KD and 72/73 KD heat shock protein in atopic dermatitis:
      comparison with those in normal skin and contact dermatitis.
AB  - The expression of Heat Shock Protein (HPS) 72/73, HSP65 and HSP27 in skin lesions
      of atopic dermatitis (n = 21) was studied and compared with that in contact
      dermatitis (n = 18) and normal skin (n = 9). Keratinocytes in the whole epidermis
      expressed both HSP65 and HSP72/73 with a membranous, cytoplasmic or
      nuclear/perinuclear staining pattern much more intensely in atopic dermatitis
      than in contact dermatitis and normal subjects. In approximately half of the
      subjects with atopic dermatitis, infiltrating cells in the dermis expressed HSP65
      and HSP72/73; this was not observed in contact dermatitis. HSP27 was expressed in
      the upper epidermis with a cytoplasmic or nuclear/perinuclear staining pattern in
      all groups. HSP27 was not expressed by infiltrating cells. A clinical evaluation
      of atopic dermatitis showed that more severe types of atopic dermatitis expressed
      more intense expression of HSP65 and HSP72/73, but not HSP27, in their skin
      lesions. These findings suggested that HSP65 and HSP72/73 may play roles in the
      pathogenesis of atopic dermatitis.

PMID- 10920583
TI  - A case of pemphigus vulgaris successfully treated with single filtration
      plasmapheresis: a correlation of clinical disease activity with serum antibody
      levels.
AB  - We report a patient with pemphigus vulgaris (PV) successfully treated with single
      filtration plasmapheresis. A 40-year-old man with PV was started on therapy with
      prednisolone (PSL). Although the dosage of PSL was doubled, and both cyclosporin
      A (CyA) and pulse therapy were added, the disease was not controlled. After
      single filtration plasmapheresis began, most of the eroded lesions on the trunk
      reepithelialized. A switch to double filtration was followed by recurrence.
      Finally, additional treatments with single filtration plasmapheresis were
      required to obtain remission. To evaluate the efficacy of the treatment,
      circulating antibodies were measured by immunofluorescence (IIF) and enzyme
      linked immunosorbent assays (ELISAs) using recombinant desmoglein (Dsg) 3. IIF
      titer and the ELISA scores correlated with the clinical disease activity. It is
      suggested that ELISA was more sensitive than IIF.

PMID- 10920584
TI  - Kangal hot spring with fish and psoriasis treatment.
AB  - The effect of "Kangal Hot Spring with Fish" in the treatment of psoriasis is
      investigated. The study was carried out on 87 patients with psoriasis vulgaris
      and the patients were evaluated by a dermatologist for 21 days. The evaluation of
      the disease was performed using PASI (Psoriasis Area and Severity Index) scores.
      Recurrences were investigated in the patient population, who had been previously
      treated in the same hot spring. The first examination scores were significantly
      higher than the scores of the 3, 6, 9, 12, 15 and 21 days after treatment (p <
      0.01). Longer remission periods, when compared to the topical corticosteroid
      treatment, expressed by the 35 patients previously treated in hot spring (p <
      0.01). Spa therapy under observation of a dermatologist may be effective and
      useful for psoriasis vulgaris patients.

PMID- 10920585
TI  - A case of classic Kaposi's sarcoma in a Japanese man: detection of human herpes
      virus 8 (HHV-8) infection by means of polymerase chain reaction and
      immunofluorescence assay.
AB  - The recently discovered human herpes virus 8 (HHV-8) has been implicated in the
      pathogenesis of Kaposi's sarcoma (KS). Because classic KS in Japan is rare and
      the detection of HHV-8 DNA by polymerase chain reaction (PCR) has been successful
      only in limited cases, the frequency and role of HHV-8 infection in KS in Japan
      remain unclear. Herein we report a case of classic KS in a Japanese man whose HHV
      8 infection was confirmed by the detection of lesional viral DNA and serum
      antibodies against lytic antigen.

PMID- 10920586
TI  - Postoperative hyponatremia in a patient with ACTH-producing Merkel cell
      carcinoma.
AB  - Merkel cell carcinoma is characterized by specific neuroendocrine features and
      the expression of several neuropeptides. We report a case of Merkel cell
      carcinoma with post-surgical hyponatremia in an 85-year-old Japanese woman. A
      tumor on the left cheek histopathologically showed the characteristics of Merkel
      cell carcinoma together with Bowen's disease. Although an increased level of ACTH
      was found both in the tumor and in the peripheral blood, the postoperative
      hyponatremia in our patient seems more likely to have been caused by the stress
      of the operation and indapamide, considering that the ACTH level in the tumor was
      much lower than those in other ectopic ACTH-producing tumors in previous reports.

PMID- 10920587
TI  - A case of toxic epidermal necrolysis-type drug eruption induced by oral lysozyme
      chloride.
AB  - We report a case of toxic epidermal necrolysis-type drug eruption. A 23-year-old
      man took an oral over-the-counter preparation for the common cold. A few days
      later, generalized erythema developed with systemic malaise and pain. A multiple
      blister formation followed, and Nikolsky's sign was noted on each blister. A
      lymphocyte stimulation test (LST) with the patient's peripheral lymphocytes
      strongly suggested that the eruption was attributable to lysozyme chloride which
      was included in the preparation taken. Following an intravenous drip of
      betamethasone for two weeks, the eruptions improved favorably.

PMID- 10920588
TI  - Quinolone drug rash in a patient with infectious mononucleosis.
AB  - Infectious mononucleosis and the associated ampicillin rash are well documented.
      The case of a patient with infectious mononucleosis who was treated with
      levofloxacin and developed a rash similar to the ampicillin rash is reviewed. The
      exact mechanism is not understood. With closer observation, physicians may be
      able to recognize more cases with similar phenomena.

PMID- 10920589
TI  - Successful mapping of lymphorrhea using patent blue dye after lymph node
      dissection for malignant melanoma.
AB  - Patent blue is a dye that has been used for intraoperative lymphatic mapping. We
      used this mapping method on a patient with lymphorrhea after groin dissection. We
      easily detected the lymphatic channel causing lymphorrhea and successfully
      ligated it. This technique may have great merit for treating of lymphorrhea.

PMID- 10920590
TI  - Double involvement of extramammary Paget's disease in the genitalia and axilla.
AB  - We here reported a case of an 82-year-old man with double involvement of
      extramammary Paget's disease in the genitalia and axilla. Physical examination
      revealed erythema and reddish tumors on the pubic area and scrotum and irregular
      shaped erythema on the left axilla. The skin biopsy sample from the genital area
      showed Paget's cells in the epidermis and upper dermis. The specimen from the
      left axilla showed Paget's cells scattered in the epidermis but not in the
      dermis.

PMID- 10920592
TI  - Vitiligo vulgaris associated with hepatitis C virus.

PMID- 10920591
TI  - Delayed tissue necrosis associated with mitomycin-C administration.

PMID- 10920593
TI  - An additional case of solitary subungual glomus tumor associated with
      neurofibromatosis 1.

PMID- 10920594
TI  - Palmar erythema nodosum.

PMID- 10920595
TI  - School dropout and injecting drug use in a national sample of white non-Hispanic
      American adults.
AB  - In this study we sought to extend our previous finding of an association between
      school dropout and injecting drug use (IDU) among African Americans by testing
      the association in a sample of White non-Hispanic Americans. A nationally
      representative sample of White non-Hispanic Americans age eighteen years and
      older was drawn from public use data files of the 1995-1996 National Household
      Surveys on Drug Abuse (NHSDA). Adults with a self-report history of IDU were
      identified, and were matched to non-IDU adults in the same neighborhoods of
      residence. Conditional logistic regression was used to estimate the association
      between dropping out of high school and the occurrence of IDU. White non-Hispanic
      American high school dropouts were more likely than high school graduates to have
      injected a drug at least once. The findings of this research on non-Hispanic
      Whites are generally consistent with our earlier evidence on the association
      between educational status and a history of IDU among African-American adults.
      School dropout prevention programs may merit attention in an overall strategy of
      preventing injecting drug use and HIV/AIDS.

PMID- 10920596
TI  - An ethical code for AOD faculty: a proposed set of guidelines.
AB  - Ethical codes of conduct are accepted requirements for membership in state and
      national organizations that grant credentials to those who are employed as
      alcohol and other drug (AOD) counselors, prevention specialists, and clinical
      supervisors. It seems appropriate to explore the possibility of an ethical code
      directly linked to addiction faculty which will outline their unique educational
      responsibilities and standards. The authors suggest development and adoption of
      such an ethical code for college-level addiction studies faculty and this
      proposal is offered as a move toward that possibility.

PMID- 10920597
TI  - Results of a pilot program for training bar staff in preventing aggression.
AB  - One hundred and twenty-one staff from eight bars in Ontario, Canada participated
      in a three-hour training program that used a peer learning model to teach problem
      solving skills regarding the prevention and management of aggressive behavior in
      bars. Participants showed significant positive changes in knowledge and attitudes
      regarding effective approaches to preventing aggression. The majority of
      participants reported that the training made them think about ways they handed
      problem situations and that they would change the way they handle problems in the
      future. Participants rated most aspects of the training as very useful,
      especially the group discussion. The program illustrates the potential for
      increasing skills and knowledge of bar staff in preventing aggression and
      associated injury.

PMID- 10920598
TI  - The effects of perceived parental behaviors, attitudes, and substance-use on
      adolescent attitudes toward and intent to use psychoactive substances.
AB  - The effects of parental behaviors, attitudes, and drug-use as perceived by
      adolescents on the latter's attitudes toward and intent to use psychoactive
      substances were studied. Perceived parental rejection, acceptance, and attitudes
      significantly differentiated between adolescents who reported favorable attitudes
      toward and high intent to use substances and those who expressed less favorable
      attitudes. On most parameters, the father's influence was significant, whereas
      the effect of the mother did not reach significance. Positive and significant
      relationships were also found between perceived parental rejection, acceptance,
      and attitudes and adolescent attitudes and intent to use psychoactive substances.
      No relationships were found between controlling parental behavior and adolescent
      attitudes and intent to use psychoactive substances. The role of the parents, as
      well as implications of the findings for prevention are discussed.

PMID- 10920599
TI  - Reducing HIV/AIDS high-risk behavior among injection drug users: peers vs.
      education.
AB  - This study examines the effects of peer groups and education on risk behavior for
      HIV among injection drug users (IDUs). The sample consisted of 682 participants
      in the Eastern Connecticut Health Outreach project, which compares traditional
      and peer-driven outreach interventions for IDUs. Participants are educated about
      safer injecting, subsequently administered a risk-reduction knowledge test, and
      given an extensive interview. Logistic regression shows that education alone is
      not a significant factor in reducing risky behavior in IDUs among the behaviors
      studied. A significant interaction was found between peer support for safer use
      and personal saliency of peer attitudes for both syringe and water sharing.
      Neither peer attitudes nor education affected cooker sharing. These results
      suggest that while education may be an important component in any intervention,
      it is not alone sufficient to reduce risky behavior. Our findings suggest that
      peer-directed interventions may be useful in reducing some forms of risk behavior
      among IDUs.

PMID- 10920600
TI  - Evaluation of a family-based substance abuse prevention program targeted for the
      middle school years.
AB  - A family-based substance abuse prevention program was evaluated which emphasizes
      family cohesion, school and peer attachment, self-esteem, and attitudes about
      adolescent use of alcohol and tobacco. The program was implemented in rural
      communities and targeted families with students entering middle or junior high
      school. Baseline surveys were conducted with students and parents in four schools
      and were readministered one year later. Because the program was voluntary, a
      quasi-experimental design was used to compare participants (29 students and 28
      parents) and nonparticipants (268 students and 134 parents). Analyses of
      covariance indicated that student participants, as compared to nonparticipants,
      had higher family cohesion, less family fighting, greater school attachment,
      higher self-esteem, and believed that alcohol should be consumed at an older age
      at the one year follow-up. There were fewer significant results for parent
      participants. Strategies for involving parents in prevention programs are
      discussed.

PMID- 10920601
TI  - Outcomes associated with service involvement among disengaged youth.
AB  - This pilot study examined outcomes of a school-based effort to promote bonding to
      the conventional mainstream by integrating socially disengaged youth with
      conventional peers in a service activity. A sample of forty-two ninth-graders in
      four schools achieved significant improvements in attendance, achievement,
      ratings of social-academic competence and conventionality, and in positive peer
      associations, which protect against risk for problems such as dropout,
      delinquency, and substance abuse. Comparisons of improvements in school
      performance with changes in performance exhibited by a group of similar peers
      indicate that effects were probably not due to the effects of maturation over the
      ninth-grade year. Findings lend tentative support to the notion that social
      bonding is enhanced through opportunities for service, and justify efforts to
      develop and study methods for incorporating service components in school
      programs. Recommendations for further experimental study addressing design
      limitations of this pilot study are discussed.

PMID- 10920602
TI  - A typology of St. Louis arrestees surveyed through the arrestee drug abuse
      monitoring (ADAM) program.
AB  - Past research has demonstrated that the characteristics of substance abusers vary
      considerably. Often, however, addicts are considered members of a single,
      homogeneous group. These erroneous designations may indeed prevent the successful
      rehabilitation of substance abusers. In the present study, hierarchical and K
      means cluster analyses are used to identify a typology of substance users from a
      sample of 1,580 St. Louis arrestees surveyed through the Arrestee Drug Abuse
      Monitoring (ADAM) Program. Five clusters are yielded in the present analysis. The
      analyses illustrate not only that drug-using classifications differ between
      criminal and non-criminal populations, but that arrestee populations themselves
      vary interjurisdictionally. Given these findings, implications for local and
      regional drug treatment programs are assessed.

PMID- 10920603
TI  - The interaction and adhesive mechanisms between axon and Schwann cell during
      central and peripheral nerve regeneration.
AB  - It is well known that the injured mammalian PNS can successfully regenerate,
      while the CNS such as the optic nerve of adult mammals is incapable of
      regeneration. It is now generally accepted that the inability of CNS neurons to
      regenerate appears to be caused by the glial environment made up of astrocytes
      and oligodendrocytes. However, recent studies show that such CNS neurons have the
      intrinsic capacity to regenerate which is triggered by an experimental
      replacement of inhibitorial glial environment to peripheral nerve segment. Thus,
      the PNS environment is suitable not only for the regeneration of PNS itself, but
      also for the elicitation of CNS regeneration. Schwann cell is the major component
      of PNS, which plays a central role both in PNS and CNS regeneration by producing
      various kinds of functional substances. The contact of axons to Schwann cells
      based upon the structural and molecular linkages seems to be indispensable for
      stable and successful regeneration. In addition to cell adhesion molecules,
      Schwann cells utilize short focal tight junctions to provide morphological
      stabilization of the contact with the elongating axon, as well as small scale gap
      junctions to facilitate traffic of substances between them. Thus, nerve
      regeneration is not a simple phenomenon of axonal elongation on the part of the
      Schwann cell membrane, but is based on direct and dynamic communication between
      the axon and the neighboring Schwann cell, which may be partly associated with
      the mechanisms of neural regeneration.

PMID- 10920604
TI  - Two-dimensional changes of muscle fiber types in growing rat hind limb.
AB  - In the present study, we examined the changes in two-dimensional distribution of
      fiber types in the whole area of the rat skeletal muscle and the effect of growth
      on this distribution. Muscles of rats aged 3 (body weight 58 g), 4 (89 g), 8 (276
      g), 12 (312 g), 18 weeks (368 g), and 6 months (450 g) were stained for
      myofibrillar adenosine triphosphatase (mATPase) with preincubation at pH 4.35.
      Muscle fibers were classified into type I (slow oxidative), IIA (fast oxidative),
      IIB (fast glycolytic), and IIX (fast oxidative glycolytic). The x-y coordinates
      of each fiber were used to analyze the growth-related changes using an image
      analyzing system. In the tibialis anterior (TA) muscle, type I fibers were
      predominant in the deep and middle regions at 3 to 4 weeks of age, but became
      restricted to the deeper region with growth. In the extensor digitorum longus
      (EDL) muscle, type I fibers were predominant in the deep region at 3 to 8 weeks
      of age, but decreased gradually with growth and completely disappeared at 6
      months of age. Compared with the TA and EDL, type I fibers of the soleus (SOL)
      muscle were spread throughout the muscle and the number of these fibers tended to
      increase with growth. Type IIA and IIX fibers of the SOL decreased in number and
      became restricted to the superficial region with growth. No type IIB fibers were
      detected in the SOL throughout life. Our results indicated that the growing
      process influences the distribution, proportion and characteristics of individual
      muscle fiber types in the rat hind limb muscles.

PMID- 10920605
TI  - Ultrastructural and functional studies of cryopreserved rat lungs for
      transplantation using a new hyperosmolal solution.
AB  - One of the most promising approaches for extending the period of tissue or organ
      preservation is to induce a state of cryopreservation. In this report, to achieve
      successful lung cryopreservation, we created a new hyperosmolal solution (HOS)
      containing 10% glycerol and 5% dimethyl sulfoxide (Me2SO). We compared the
      efficacy of HOS with that of Euro-Collins solution (ECS) in rat lung
      cryopreservation from an ultrastructural and functional point of view. Using ECS,
      widespread damage to the air-blood barrier was observed even in the lungs
      cryopreserved at -10 degrees C. At -196 degrees C, the capillary lumen was
      obstructed with a mesh-like formation derived from deteriorated endothelial
      cells. In contrast, using HOS, the cryopreserved lungs at -10 degrees C were
      characterized by well preserved endothelial cells and basal laminae, despite the
      existence of focal cytoplasmic swelling of epithelial cells. The endothelial
      cells and basal laminae were successfully preserved up to -196 degrees C.
      Considering the survival rates at day 7 after cryopreserved lung transplantation,
      the grafted left lungs functioned normally only when perfused by and preserved in
      HOS at -10 degrees C. These findings demonstrate that HOS was effective not only
      for endothelial cells and basal laminae up to -196 degrees C, but also lung
      cryopreservation at least up to -10 degrees C.

PMID- 10920607
TI  - Two case reports of the right-sided aortic arch.
AB  - Two cases of right aortic arch with the left subclavian artery as its last branch
      were found in cadavers of 66- and 80-year-old Japanese males during the 1995 and
      1996 dissection for students at Tokyo Dental College. In both cases, the
      esophagus and trachea were surrounded by a vascular ring which consisted of the
      aortic arch and arterial ligament. The left common carotid artery arose from the
      ascending aorta as the first branch and crossed ventral to the trachea in a left
      cephalic direction. In The second branch of the aorta, which was the right common
      carotid artery, the aortic arch ran in a dorsal direction, passing between the
      esophagus and vertebra after branch out the right subclavian artery. The left
      subclavian artery arose dorsal to the esophagus, and there was an aortic
      diverticulum between the left subclavian artery and the descending aorta. The
      arterial ligament communicated between the left pulmonary artery and the arterial
      diverticulum. The trachea and esophagus were consequently encircled by the
      vascular ring. Both of the present cases were of the N-type, according to the
      classification by Adachi-Williams-Nakagawa (Group IIIB1 type by Stewart, 1964).

PMID- 10920606
TI  - [Non-cholinergic projections from basal forebrain to medial limbic cortex of
      rat].
AB  - Laminar distribution and synaptic organization of non-cholinergic projections to
      the medial limbic cortex from the basal forebrain (BF) were studied in rats. To
      eliminate BF cholinergic neurons selectively, a immunotoxin, 192IgG-saporin, was
      injected into lateral ventricle, and 7 days later, to label the remaining non
      cholinergic elements, Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected
      into BF. In rats injected with the toxin, PHA-L labeled fibers, presumably
      originating from the remaining non-cholinergic neurons, were distributed in
      layers V-VI of the medial limbic cortex. Ultrastructural observation showed that
      the PHA-L labeled fibers were classified into two categories. One class of the
      axons provided with numerous passant boutons, whereas the other carried fewer
      passant varicosities. Both classes of terminals were found to make symmetrical
      synaptic contacts predominantly with dendritic shafts, together with a large
      number of degenerating terminals making asymmetrical synapses with dendritic
      spines, presumably cholinergic in nature. These results suggest that non
      cholinergic projections from the BF exert a modulatory effect directly on
      cortical neurons in the medial limbic cortex.

PMID- 10920608
TI  - The value of DALY life: problems with ethics and validity of disability adjusted
      life years.

PMID- 10920609
TI  - A woman with leprosy is in double jeopardy.
AB  - The double jeopardy associated with female leprosy patients is the central theme
      underpinning this essay. It constitutes a combination of biological factors
      unique to women and culturally defined bias, resulting in more stigmatization and
      isolation for women. Having examined the female immunological response and
      biological roles, the essay continues by focusing on the gender-culture
      perspective of leprosy. It draws upon an historical analysis of the experiences
      of Indian and African women to illustrate the ways in which gender roles impact
      upon health education and the utilization of health care services. Concluding
      comments suggest strategies that might improve female leprosy patient status, and
      views towards future research.

PMID- 10920610
TI  - Relapses in multibacillary leprosy patients: effect of length of therapy.
AB  - Two groups of MB leprosy patients, one treated to the point of smear negativity
      (TSN) and the other given therapy for fixed duration (24 doses of WHO MB regimen)
      (FDT), were compared for relapse rates during treatment and in the post-treatment
      period. During the follow-up of 980.2 person years in 260 patients treated with
      FDT, 20 relapses (2.04/100 patient years) were observed. In the other group of
      301 patients, who received therapy till smear negativity, 12 relapses in 1085.46
      person years (1.10/100 patient years) occurred. Comparison of survival rates
      (without relapse) has shown that although there is no difference up to 4 years,
      the risk of relapse was significantly higher on longer follow-up in the FDT
      group. In addition, when patients were compared on the basis of initial bacterial
      load, it was found that the relapse rates in patients with BI > or = 4 was
      significantly higher (P < 0.01) in the FDT group as compared to those receiving
      treatment till the point of smear negativity (4.29 versus 1.27/100 patient
      years). All the relapsed patients responded to retreatment with the same drug
      combination, indicating that the exacerbation in their condition was because of
      insufficient treatment. It is suggested that to prevent or reduce relapses,
      treatment where feasible would be continued till smear negativity, at least in
      patients with high BI.

PMID- 10920611
TI  - The treatment of acute nerve function impairment in leprosy: results from a
      prospective cohort study in Bangladesh.
AB  - In this paper, the outcome of 132 patients having acute nerve function impairment
      (NFI) is reported at 4 and 12 months after the start of prednisolone treatment.
      In all, 68% of sensory nerves and 67% of motor nerves showed improvement at 12
      months, with no statistical difference in responsiveness of various nerves to
      prednisolone. Duration and severity of impairment were not found significant
      predictors of treatment outcome. A core of 32% of impaired nerves did not respond
      to prednisolone, and 12% of impaired nerves had functional deterioration despite
      treatment. The mean eye-hand-foot (EHF) score improved from 2.02 to 1.33 in the
      treatment group (median score improved from 2 to 1). Approximately one-third of
      all patients requiring prednisolone treatment did not receive it, an important
      reason being that some patients developed new NFI against a background of chronic
      impairment, and were thus overlooked. The 'unjustly untreated' group of patients
      had a spontaneous sensory nerve function improvement rate of 62% and a motor
      nerve function improvement rate of 33% at 12 months from onset of NFI. The EHF
      score showed no statistically significant improvement.

PMID- 10920612
TI  - The age-dependent deterioration in light touch sensation on the plantar aspect of
      the foot in a rural community in India: implications when screening for sensory
      impairment.
AB  - Regular testing for impaired sensation is important in the management of diseases
      that can cause progressive nerve damage, such as leprosy. It has been shown that
      light touch sensibility decreases with age in the hands of healthy individuals,
      but little research has been undertaken to assess possible changes in the feet in
      developing countries. This information is needed to allow an appropriate level of
      sensation to be chosen when screening for nerve damage in the foot. To clarify
      this, a cross-sectional study on male adults was carried out in the rural town of
      Salur, Andhra Pradesh, India. A range of Semmes-Weinstein monofilaments were
      employed at 12 locations on the foot to determine sensation to light touch
      stimuli in individuals from each decade of adult life. It was found that in this
      population, sensibility threshold in the foot increases with age and this was
      noted in both soft and callous skin. This shows the increase was due to
      neurological factors, not merely due to an increase in callous deposition with
      advancing age. In the majority of individuals in their fifties and sixties, the
      callous skin at the forefoot and heel was unable to detect the 5.07 monofilament
      (equivalent to 8-12 g), previously recommended as a method to screen for plantar
      neuropathy. All areas of all feet were able to detect the 5.46 filament
      (approximately 30 g). The size of this study (54 individuals) prevents the
      determination of definitive normal ranges for each decade of life in this
      population. However, it does demonstrate the degree to which sensation
      deteriorates with age and could be used as an approximate guide when interpreting
      the results of sensory testing in similar rural areas of the developing world.

PMID- 10920613
TI  - Mycobacterium w vaccine, a useful adjuvant to multidrug therapy in multibacillary
      leprosy: a report on hospital based immunotherapeutic clinical trials with a
      follow-up of 1-7 years after treatment.
AB  - A vaccine based on autoclaved Mycobacterium w was administered, in addition to
      standard multidrug therapy (MDT), to 156 bacteriologically positive, lepromin
      negative multibacillary leprosy patients compared to a well matched control group
      of 145 patients with a similar type of disease who received a placebo injection
      in addition to MDT. The MDT was given for a minimum period of 2 years and
      continued until skin smear negativity, while the vaccine was given at 3-month
      intervals up to a maximum of eight doses. The fall in clinical scores and
      bacteriological indices was significantly more rapid in vaccinated patients, from
      6 months onward until years 2 or 3 of therapy. However, no difference was
      observed in the fall in bacteriological index in the two groups from year 4
      onwards. The number of LL and BL patients released from therapy (RFT) following
      attainment of skin smear negativity, after 24-29 months of treatment was 84/133
      (63.1%) in vaccinated and 30/120 (25.0%) in the placebo group; the difference was
      highly statistically significant (P < 0.0001). In all, 90.2% patients (146/162)
      converted from lepromin negativity to positivity in the vaccine group, as against
      37.9% (56/148) in the placebo group. The average duration of lepromin positivity
      maintained following eight doses of vaccine administered over 2 years was 3.016
      years in the vaccine and 0.920 years in the placebo group. Histological upgrading
      after 2 years of treatment in the LL type was observed in 34/84 (40.5%) cases in
      the vaccine and 5/85 (5.9%) cases in the placebo group, the difference being
      statistically significant (P < 0.001). The incidence of type 1 reactions was
      significantly higher (30.5%) in the vaccine group than (19.7%) in the placebo
      group (P = 0.0413); the difference was mainly observed in LL type (P = 0.009).
      The incidence of type 2 reactions was similar (31.8 and 34.6%) in vaccine and
      placebo groups. The vaccine did not precipitate neuritis or impairments over and
      above that encountered with MDT alone. After 5 years of follow-up following RFT,
      no incidence of bacteriological or clinical relapses was observed in both groups.

PMID- 10920614
TI  - Reactional states and neuritis in multibacillary leprosy patients following MDT
      with/without immunotherapy with Mycobacterium w antileprosy vaccine.
AB  - A vaccine based on autoclaved Mycobacterium w was administered, in addition to
      standard multidrug therapy (MDT), to 157 untreated, bacteriologically positive,
      lepromin negative multibacillary leprosy patients, supported by a well matched
      control group of 147 patients with similar type of disease, who received a
      placebo injection in addition to MDT. The MDT was given for a minimum period of 2
      years and continued until skin smear negativity, while the vaccine/placebo was
      given at 3-monthly intervals up to a maximum of eight doses. The incidence of
      type 2 reaction and neuritis during treatment and follow-up showed no
      statistically significant difference in the vaccine and placebo groups. The
      incidence of type 1 reaction (mild in most cases), however, was higher in the
      vaccine group (P = 0.041, relative risk ratio 1.79), considering LL, BL and BB
      leprosy types together, and considerably higher (P = 0.009) in LL type, probably
      because of confounding due to higher number of patients with previous history of
      reaction in this group. The occurrence of reactions and neuritis in terms of
      single or multiple episodes was similar in the vaccine and placebo groups. The
      association of neuritis and reactions, as well as their timing of occurrence
      (during MDT or follow-up), was also similar in the two groups, with more than 90%
      of occurrences taking place during MDT. The incidence of reversal reaction was
      significantly higher among the males in the vaccine group (34.5% versus 8.3%, P =
      0.019). Patients with high initial BI (4.1-6.0) showed higher incidence of
      reactions (70.3%) as compared to those with medium (2.1-4.0) and low (0.3-2.0) BI
      where the reactions were observed with a frequency of 56.1% and 38.8%,
      respectively. However, unlike reactions, neuritis incidence did not seem to be
      affected by initial BI to the same extent in the vaccine group, with frequencies
      of 35.3%, 36.3% and 25.9% in the three mentioned BI ranges. Overall, the vaccine
      did not precipitate reactional states and neuritis over and above that observed
      with MDT alone.

PMID- 10920615
TI  - Leprosy elimination at sub-national level.
AB  - New strategies for the countries that have already achieved the elimination goal,
      which includes the great majority of the endemic countries, are needed. There is
      current concern in these countries about the reduction in the political-technical
      commitment when the goal is achieved and the possibility of the re-emergence of
      the disease. A review of the literature on the leprosy post-elimination strategy
      is done. The proposal to estimate the true prevalence using hidden prevalence
      based on late diagnosis of the new cases is made. Suggestions are explored for
      strategies of the work after elimination at national level is attained such as
      the stratification at the first sub-national level, using estimated true
      prevalence. It is considered necessary to define strategies for the post
      elimination phase with the aim of continuing to the long-term objective of the
      interruption of transmission and the consequent leprosy eradication.

PMID- 10920617
TI  - Unusual fixed drug eruption due to rifampicin.

PMID- 10920616
TI  - A scholarship project for the children of leprosy patients in Turkey.
AB  - Most of the leprosy patients in Turkey live in the rural areas of Eastern and
      South-Eastern Anatolia. Those living in the suburbs of the big cities of the
      Western parts of the country have come there by immigration. Nearly all patients
      are very poor; they have no land, or only a small amount of soil for cultivation.
      The incidence of deformities in our patients is high, excluding them from regular
      employment and a source of income. In Turkey, it is obligatory to attend primary
      school, but after that education has to be paid for, and the poor families of
      leprosy patients find it difficult to continue the education of their children.
      As the 'Society for the Struggle Against Leprosy', based in the Istanbul Leprosy
      Hospital at Bakirkoy, we have developed a project to enable patients to continue
      sending their children to school, whilst at the same time asking the mothers to
      seek advice and guidance on family planning. The outset objective of this project
      was to enable children and young people, who otherwise have almost no chance of
      continuing education, to pursue education at secondary, high school and
      university levels. It was envisaged that in the long term educated children would
      be able to find a job and provide effective care and support for parents and
      other members of the family. This paper describes the administrative and other
      measures adopted and the results of the project from 1995 to 1998, during which a
      total of 545 children have been supported at an overall cost of US$107,378. The
      scholarship project has so far been remarkably successful in Turkey and it is
      hoped that it may provide a model for similar approaches in other countries. An
      unexpected and extremely encouraging finding has been that females now exceed
      males in this project and are increasing at all levels, including university
      entrance.

PMID- 10920618
TI  - [Amendments to Directive 90/394/CEE and effects on chapter VII of Law 626/94].
AB  - The European Union (EU) has recently twice amended the framework Council
      Directive 90/394/CEE on the protection of workers from risks related to exposure
      to carcinogens at work: protective measures were extended to category 1 and 2
      mutagens; a new carcinogenic agent was identified in "work involving exposure to
      hardwood dusts" and three exposure limit values were fixed for carcinogens. The
      EU Member States are required to incorporate amending Directives into national
      legislation not later than 29 April 2003. Italy acknowledged these directives by
      the Decree 66/00 of the 25/2/2000. In this paper the development and the
      evolution of European legislation in the twenty years from 1980 to 2000 are
      overviewed: first, occupational exposure limits were defined and introduced for
      harmful chemicals, then for occupational carcinogens and later three binding
      limit values for benzene, VCM and hardwood dusts were fixed. The paper attempts
      to identify the expected problems and advantages that incorporation of the
      amending Directives will have on the protection of workers from carcinogenic
      risk.

PMID- 10920619
TI  - [Measurement of N-methylformamide in occupational exposure to N,N
      dimethylformamide].
AB  - N,N-dimethylformamide (DMF) is a solvent that is widely used in industry. The
      major occupational sources of exposure results from production of synthetic
      leather. The main metabolite formed in both man and animals is N-hydroxymethyl-N
      methylformamide. Demethylation leads to N-methylformamide (NMF) and formamide and
      also to a small extent to hydroxy-methylformamide. All the metabolites are
      excreted in urine, as are very small amounts of the unchanged substance. N-acetyl
      S-(N-methyl-carbamoyl)-cysteine can be determined in urine as a further
      metabolite. We conducted this biomonitoring study with the aim of evaluating the
      correlation between the excretion of N-methylformamide (mainly from N
      hydroxymethylformamide) and levels of exposure to N,N-dimethylformamide among
      occupationally exposed people. The mean time-weighted average (TWA) exposure was
      about half (13.5 mg/m3) of the current threshold limit value, the range of the
      values varying from 0.4 to 75.2 mg/m3. A linear equation existed between urinary
      NMF concentration and DMF concentration in the environment. The findings show
      that the urinary NMF concentration can be used as an appropriate biological
      exposure index. The authors suggest for occupationally exposed subjects, a
      urinary NMF concentration corresponding to the time-weighted average of the
      threshold limit value of 39.9 mg/l (37.2 mg/g creatinine) and a 95% lower
      confidence limit (biological threshold) of 23.4 mg/l (22.2 mg/g creatinine).

PMID- 10920620
TI  - [Symptoms of ocular discomfort and microclimate: epidemiologic and environmental
      survey in operating rooms].
AB  - An epidemiological investigation regarding the ocular symptoms of 213 subjects
      working in the operating theatres of a hospital of the eastern Sicily was
      conducted. Information was gathered via a questionnaire designed to identify the
      ocular symptoms that occurred most frequently during working hours in the
      operating theatre. The questionnaire was administered by a specialist in
      Occupational Health, before any decision was made to investigate the indoor air
      quality. The microclimate parameters (temperature, relative humidity, number of
      air changes/hour, air velocity, illumination levels) of the operating theatres
      were also studied. The results of the epidemiological investigation showed that
      154 subjects out of 213 (72.3%) reported a lack of eye comfort. The most
      frequently reported symptoms were fatigue (35.21%) and heaviness (34.27%),
      followed by burning (25.82%), redness (25.35%), lacrimation (17.84%), itching
      (2%), blinking (20%), foreign body sensation (19%) and photophobia (10%). The
      study of the indoor climate of the operating theatres showed that the number of
      air changes/hour and illumination level were not consistent with those
      recommended by the Italian Regulatory Authority. Others parameters were
      considered to be satisfactory. The Authors conclude that the low illumination
      level may be responsible for the high percentage of subjects suffering from eye
      fatigue and heaviness. The ineffective rate of room air exchange, possibly
      interacting with chemicals and aerosols, is thought to be responsible for the
      other ocular symptoms experienced by the workers. The present study suggests that
      the operating theatre environment might be a cause of the ocular discomfort often
      complained of by health care workers. Further studies are needed in this area.

PMID- 10920622
TI  - [Case study of a population of subjects in Sicily operated for hydatidosis:
      correlation with profession and living environment].
AB  - The aim of the study was to evaluate significant factors in the spread of
      echinococcosis in certain areas of Sicily. Data was obtained from operating
      registers of four surgical departments of the University Hospital of Palermo
      which covered 104 subjects, 57 women and 47 men, who underwent an operation for
      echinococcosis cysts in the period January 1996-June 1999. About 15% of these
      subjects were farmers, slaughterers, shepherds or gardeners and more than 80%
      lived in rural areas. The study showed that echinococcosis is still widespread in
      Sicily, at higher rates than the population, physicians and Health and safety
      Institutes generally believe. The place of origin is of particular importance
      because in rural areas it is very easy to be contaminated by infected animals or
      eat vegetables contaminated by parasitic eggs.

PMID- 10920621
TI  - [Presence of asbestos in naval vessels: study of airborne fiber concentrations on
      Italian railways ferry boats].
AB  - Asbestos has been widely used on ships as an insulating material due to its fire
      resistant and sound-absorbent properties. It was therefore deemed appropriate to
      measure the concentrations of airborne asbestos fibres on two ferries in regular
      service on the Civitavecchia-Golfo Aranci route. Decontamination work had been
      carried out on these vessels in order to remove, as far as possible, or to
      confine asbestos. Between 1994 and 1998, the Ultrastructures Laboratory of the
      Istituto Superiore di Sanita analysed 123 samples via scanning electron
      microscopy (SEM) with elementary dispersion X spectroscopy (EDXS). The results
      showed that in 98.4% of the samples concentrations in the air were below 2
      fibres/litre, which is the value set by Ministerial Decree of 6/9/94 for
      buildings to qualify for effective decontamination status. Concentrations above
      this value, between 2 and 10 fibres/litre, were found in one ferry engine room,
      where workers were not continuously present since a remote control box was
      installed there. The results show that there is no environmental dispersion of
      asbestos fibres in usual navigation conditions; the situation is comparable to
      that in buildings where asbestos-containing safety materials have been used and
      that are subject to period checks in accordance with the guidelines included in
      Ministerial Decree of 6/9/94. Legislation is deemed necessary to make law 257/92
      applicable to naval vessels in order to define univocal criteria for risk
      evaluation, checking, maintenance and custody procedures of asbestos-insulated
      vessels, and procedures for each job on board involving handling or removal of
      asbestos-containing material.

PMID- 10920623
TI  - [Post-traumatic aneurysm of the hand: 3 clinical cases].
AB  - Three cases of ulnar post-traumatic aneurysms of the hand as a consequence of
      occupational injury are reported. In two cases arteriography examination
      confirmed the presence of ulnar aneurysm while in the third case we performed
      only Duplex-scanning. To avoid complications treatment was surgical, consisting
      of resection of the lesion with end-to-end anastomosis. Ulnar artery patency was
      confirmed by Duplex-scanning in the follow-up period and the patients were able
      to return to their jobs.

PMID- 10920625
TI  - [A century of occupational medicine in Italy].

PMID- 10920624
TI  - [Occupational medicine in Italy: a look to the past, and several observations on
      the future].

PMID- 10920626
TI  - [Health surveillance of subjects exposed to asbestos in the past].

PMID- 10920627
TI  - A civilian-military virtual public health laboratory network.

PMID- 10920628
TI  - The need for a military public health laboratory symposium.
AB  - The Department of Defense Global Emerging Infections Surveillance and Response
      System has a mission to identify vulnerabilities in the military health system
      related to the occurrence of emerging infectious diseases. Public health
      laboratory (PHL) functions are critical to the detection and control of emerging
      infectious diseases and were assessed. Four important services were evaluated:
      (1) surveillance for antibiotic resistance, (2) laboratory-based infectious
      disease surveillance, (3) provision of diagnostic services for uncommon
      infections, and (4) specimen referral and information transfer within a defined
      PHL infrastructure. Initial assessments identified several shortcomings and a
      lack of information about PHL functions. Therefore, a PHL symposium was held in
      September 1999 to define the state of civilian and military PHL functions,
      identify problems and interventions, and encourage civilian-military networking.
      After the symposium, selected attendees met in two workshop groups. One addressed
      the first two functions; the other addressed the last two.

PMID- 10920629
TI  - The state of public health laboratories.
AB  - Public health laboratories in the United States exist at the federal, state, and
      local level. The earliest laboratories were created in the late 1800s in the wake
      of the work of Robert Koch and Louis Pasteur. Currently, these laboratories make
      up a loosely formed network. The combined state portion of this network employs
      more than 6,000 staff members, tests more than 20 million specimens each year,
      and has a combined annual budget of more than $300 million. Public health
      laboratories are found in a variety of organizational settings. Several efforts
      have been made to define the roles of public health laboratories. Recently, the
      Association of Public Health Laboratories adopted a consensus position that has
      formally set forth the core functions, which include activities such as
      environmental testing, emergency response, surveillance, and reference services.
      Public health laboratories are being challenged with funding, new technology, and
      current issues such as bioterrorism, food safety, and antimicrobial resistance.

PMID- 10920630
TI  - The complex processes of antimicrobial resistance and the information needed to
      manage them.
AB  - Wide use of a succession of different manufactured antimicrobial agents during
      the past 60 years has prompted the eventual emergence and progressive spread
      through the world's interconnecting bacterial populations of a growing variety of
      genes expressing resistance to those agents. The complex processes that spread
      and link resistance genes into different distributions at different times and
      places are driven by antimicrobial selection and by contagion. Management of
      resistance by reducing selection and contagion in a coordinated way requires
      better information. Most of the information about the spread of resistance exists
      in laboratory files of isolates at medical centers, and the information about
      patient antimicrobial use is found in pharmacy files at the same centers. Putting
      these in a combined database at each center would give a valuable tool to each
      center's antimicrobial resistance management team. Merging such databases from
      multiple centers would provide a public health resource for benchmarking,
      overview surveillance, and general resistometrics.

PMID- 10920631
TI  - Laboratories and disease surveillance.
AB  - The U.S. communicable disease surveillance system depends on high-quality testing
      and reporting by clinical and public health laboratories (PHLs). Clinical
      laboratories offer a wide range of microbiological services, provide a large
      portion of all disease reports, and refer isolates and samples to PHLs for
      confirmation and typing. The PHLs support disease surveillance by providing
      special reference testing, serological or molecular typing to identify disease
      clusters and sources, primary laboratory services for high-risk clients, quality
      assurance and training for clinical laboratories, and testing for unique agents
      unavailable elsewhere. However, profound changes in the health care industry are
      threatening the ability of public- and private-sector laboratories to carry out
      disease surveillance activities. Isolates for typing and confirmation are less
      available, PHL surveillance testing volumes are lower, and relationships between
      clinical laboratories and PHLs have changed. The integrity of the U.S. disease
      control infrastructure depends on maintaining a complementary network of clinical
      and public health laboratories, and a national system for public health testing
      is needed.

PMID- 10920632
TI  - Electronic laboratory-based reporting for public health.
AB  - This article describes the role of laboratory-based reporting for public health
      in the United States and outlines a vision for electronic laboratory-based
      reporting (ELR). It emphasizes the importance of adoption and implementation of
      standards to the successful development of ELR. In particular, it describes the
      role of Health Level 7 as a standard for electronic message formats and the roles
      of LOINC (Logical Observation Identifiers, Names, and Codes) and SNOMED
      (Systematized Nomenclature for Human and Veterinary Medicine) as standards for
      test names and results, respectively. In addition, the article describes ongoing
      and planned ELR projects

PMID- 10920633
TI  - Bioterrorism and the importance of the public health laboratory.
AB  - Biological terrorism is a threat to the United States that public health
      laboratories cannot afford to ignore. With the ability to recognize unusual
      strains of organisms, or an increase in test requests or isolation of specific
      organisms, the public health laboratory can detect the beginning of an outbreak.
      The laboratory can also facilitate appropriate response measures with rapid
      diagnostic testing and by determining antibiotic resistance patterns. Public
      health laboratory personnel need to assess their capabilities, improve them where
      indicated, and know where to turn for assistance. As improvements in bioterrorism
      detection occur in the civilian sector, military laboratories must integrate with
      local, state, and federal health department systems. Laboratories are essential
      components in surveillance, recognition, and response for both bioterrorism and
      naturally occurring disease outbreaks.

PMID- 10920634
TI  - A national laboratory network for bioterrorism: evolution from a prototype
      network of laboratories performing routine surveillance.
AB  - The need for an enhanced network of laboratories to respond to a bioterrorism
      attack has been realized. Therefore, the Association of Public Health
      Laboratories and the Centers for Disease Control are developing a system
      involving civilian public health and private laboratories that builds on the
      existing network for routine disease surveillance. It is anticipated that most
      bioterrorist attacks will not be immediately recognized, so increased laboratory
      capabilities and communications are necessary. The laboratory network has four
      categories with different biosafety levels assigned to clearly delineate the
      correct referral route. Improving communications through World Wide Web-based
      systems will allow test results, surge capacity, and training and identification
      algorithms to be shared instantly. There are plans to expand the network to
      include standard public health surveillance and emerging infectious diseases.

PMID- 10920635
TI  - The Naval Health Research Center Respiratory Disease Laboratory.
AB  - Concern about emerging and reemerging respiratory pathogens prompted the
      development of a respiratory disease reference laboratory at the Naval Health
      Research Center. Professionals working in this laboratory have instituted
      population-based surveillance for pathogens that affect military trainees and
      responded to threats of increased respiratory disease among high-risk military
      groups. Capabilities of this laboratory that are unique within the Department of
      Defense include adenovirus testing by viral shell culture and microneutralization
      serotyping, influenza culture and hemagglutination inhibition serotyping, and
      other special testing for Streptococcus pneumoniae, Streptococcus pyogenes,
      Mycoplasma pneumonia, and Chlamydia pneumoniae. Projected capabilities of this
      laboratory include more advanced testing for these pathogens and testing for
      other emerging pathogens, including Bordetella pertussis, Legionella pneumoniae,
      and Haemophilus influenzae type B. Such capabilities make the laboratory a
      valuable resource for military public health.

PMID- 10920636
TI  - The state of antibiotic resistance surveillance: an overview of existing
      activities and new strategies.
AB  - The growing global problem of antibiotic resistance requires a worldwide
      surveillance strategy to characterize the magnitude of the problem, guide
      clinical care decisions, and assess the impact of prevention and control
      interventions. Because many existing antibiotic resistance surveillance
      activities have developed independently of one another and vary greatly in their
      focus, key organizations are promoting strategies to standardize surveillance
      activities and build collaboration to promote effective global surveillance. With
      medical facilities operating throughout the world to support a highly mobile
      beneficiary population, the Department of Defense's Military Health System could
      benefit from partnership with civilian efforts to achieve global antibiotic
      resistance surveillance. This article's overview of existing surveillance
      activities and new strategies provides information requisite to the Department of
      Defense undertaking of development of a worldwide antibiotic resistance
      surveillance program to complement and integrate with civilian programs.

PMID- 10920637
TI  - Antibiotic resistance monitoring: a laboratory perspective.
AB  - Efficient monitoring of antimicrobial resistance (AR) can produce timely and
      important data and information that will benefit patients and could assist in the
      detection of a bioterrorist event. The microbiology laboratory staff of the
      largest U.S. Air Force medical facility attempted to improve AR monitoring at
      their hospital by reviewing their current capabilities and the capabilities of
      other available monitoring systems. The systems reviewed included the DataTrac
      System (Vitek bioMerieux, Hazelwood, Missouri) and the military Composite Health
      Care System, which were already in use, and the WHONET 5 (World Health
      Organization, Geneva, Switzerland) and The Surveillance Network (MRL
      Pharmaceutical Services, Herndon, Virginia). The Surveillance Network was
      selected for incorporation into the hospital AR monitoring program with
      modifications to comply with military command requirements. Information gathered
      during the review and selection process are presented and may be helpful to
      others who are looking to improve their hospital AR monitoring programs.

PMID- 10920638
TI  - Antibiotic resistance: a clinician's perspective.
AB  - Since the introduction of antimicrobial agents, resistance has increased steadily
      across all classes of antibiotics. Organisms vary in susceptibility. Therefore,
      an antibiogram or susceptibility profile is needed for each infecting organism to
      determine the most appropriate antibiotic. When the infecting organism has not
      yet been identified, an informed decision can be made only by obtaining an
      accurate profile of antibiotic resistance in the hospital, the community, and, in
      some instances, the world. The appropriate use of antibiotics is correlated with
      a more favorable clinical outcome and also delays the emergence of resistance.
      Ensuring such prescribing behavior requires a multidisciplinary approach.
      Familiarity with the trends and prevalence of antibiotic resistance also
      facilitates the early identification of individuals harboring resistant
      organisms. Early isolation can then be initiated, thereby minimizing the risk of
      nosocomial cross-infection. This article offers a clinician's pragmatic view of
      antimicrobial resistance.

PMID- 10920639
TI  - Planning for the future: the Department of Defense Laboratory Joint Working Group
      and Global Laboratory Information Transfer.
AB  - The Department of Defense (DoD) Laboratory Joint Working Group plans unified
      laboratory strategy under the auspices of the Armed Forces Institute of Pathology
      Board of Governors. One goal of the Laboratory Joint Working Group is to advocate
      clinical integration through automation of data transfer between medical
      treatment facilities using the DoD standard platform, Composite Health Care
      System (CHCS). A working group project team is implementing global laboratory
      information transfer, which enables CHCS-to-CHCS communication throughout the
      DoD. A prerequisite to global laboratory information transfer is the
      standardization of laboratory test nomenclature across all CHCS systems using
      LOINC (Logical Observation Identifiers, Names and Codes). This makes possible
      easier access to information among caregivers and therapeutic and public health
      disease managers and enhances global surveillance of disease outbreaks and
      continuity of care. The end result is the first-ever electronic transfer of
      laboratory results between all DoD facilities.

PMID- 10920640
TI  - The Clinical Laboratory Improvement Program: not your ordinary regulatory
      program.
AB  - The Clinical Laboratory Improvement Amendments of 1988 (CLIA'88) established
      national standards of laboratory practice and test performance in the areas of
      registration and certification, inspection, proficiency testing, personnel
      qualifications, quality control, patient test management, and quality assurance.
      A memorandum of agreement between the Department of Health and Human Services and
      the Department of Defense (DOD) established the DOD Clinical Laboratory
      Improvement Program (CLIP) and authorized the Assistant Secretary of Defense for
      Health Affairs to develop CLIA'88-comparable regulations governing DOD
      laboratories. In implementing the DOD program, the CLIA'88 regulations were
      adopted to the maximum extent possible and modified only as required to meet
      those unique DOD missions that precluded compliance. This article provides an
      abbreviated historical background on CLIA'88/CLIP, defines the testing categories
      identified under the CLIP regulations, and briefly describes the process for
      application and requirements for compliance.

PMID- 10920641
TI  - The Department of Defense laboratory-based global influenza surveillance system.
AB  - Military global influenza surveillance began in 1976 as an Air Force program. In
      1997, the Department of Defense (DoD) Global Emerging Infections Surveillance and
      Response System expanded the program to include all services. Also included were
      local residents in areas where DoD overseas research activities operated. This
      new, worldwide DoD surveillance infrastructure provides valuable information and
      can respond quickly to outbreaks. This was demonstrated during the current
      influenza season when a suspected outbreak was reported in Panama. In less than 3
      weeks, specimens were collected, transported, and cultured, and isolates were
      subtyped and sent to the Centers for Disease Control and Prevention for further
      studies. This influenza surveillance initiative combines viral isolation,
      antigenic characterization, and molecular sequencing with clinical and public
      health management of information. The information obtained is shared with the
      Centers for Disease Control and Prevention and the World Health Organization and
      has contributed to important decisions in influenza vaccine composition.

PMID- 10920642
TI  - The Department of Defense Medical Mortality Registry.
AB  - The Department of Defense Medical Mortality Registry is being implemented at the
      Office of the Armed Forces Medical Examiner, Armed Forces Institute of Pathology,
      providing the first comprehensive medical mortality surveillance for the
      Department of Defense. The Registry attempts to obtain complete medical and
      circumstantial information on every military active duty death for medical
      surveillance and prevention research. Medical records, autopsy reports,
      eyewitness accounts, and investigative reports are reviewed to validate and
      synthesize medical, circumstantial, and risk factor information on each death.
      All military active duty deaths since 1980 are currently identified and
      classified by manner of death (accident, suicide, homicide, illness, hostile,
      undetermined). Military death rates have decreased during the past two decades by
      nearly half. About three-quarters of military deaths are attributable to injury
      (accident, suicide, homicide). The Registry creates new opportunities for
      prevention-oriented research as it collects detailed information on every
      military death.

PMID- 10920644
TI  - Military Public Health Laboratory Workshop Group B: a Department of Defense
      Directory of Public Health Laboratory Services for Infectious Agents and Public
      Health Laboratory System. 22-23 September 1999

PMID- 10920643
TI  - Military Public Health Laboratory Workshop Group A: laboratory-based
      surveillance. 22-23 September 1999

PMID- 10920645
TI  - Crystalloid resuscitation challenged.

PMID- 10920646
TI  - Concern over battlefield fluids (Feb. 2000 issue)

PMID- 10920647
TI  - Hospitalizations for all causes of U.S. military service members in relation to
      participation in Operations Joint Endeavor and Joint Guard, Bosnia-Herzegovina,
      January 1995 to December 1997.
AB  - Since December 1995, the United States has deployed military forces to Bosnia
      Herzegovina to participate for varying periods in peacekeeping operations.
      Throughout the operations, medical surveillance data have been routinely
      integrated in the Defense Medical Surveillance System. For this analysis, all
      individuals who served in the U.S. armed forces between January 1995 and December
      1997 were characterized as participants or nonparticipants in the Bosnia
      Herzegovina operations. Each participant's service was divided into
      predeployment, deployment, and postdeployment phases. End points for analyses
      were hospitalizations (all causes) in military hospitals. The crude
      hospitalization rate among nonparticipants (80.9 per 1,000 person-years [p-yrs])
      exceeded the rate among participants (56.6 per 1,000 p-yrs). Among participants,
      the crude hospitalization rate during deployment (84.4 per 1,000 p-yrs) exceeded
      the rates before deployment (54.7 per 1,000 p-yrs) and after deployment (49.9 per
      1,000 p-yrs). Proportional hazards regression procedures were used to control for
      confounding effects in comparisons of participants and nonparticipants, to
      account for transitions in deployment-phase exposures at appropriate calendar
      times, and to adjust for changes in hospitalization criteria that were
      implemented during the study. Although the crude hospitalization rate after
      deployment was lower than the rate before deployment, adjusted relative risks
      were elevated during and after deployment (relative to before deployment).

PMID- 10920648
TI  - Vision readiness at Seymour Johnson Air Force Base.
AB  - Ensuring that our forces are vision ready, i.e., they have the appropriate visual
      acuity, optical devices, and eye health to perform their mission, is essential on
      today's battlefield. A study was conducted at Seymour Johnson Air Force Base to
      determine the prevalence of vision readiness in a deploying fighter squadron. Of
      the 204 personnel screened, 59 wore glasses or contact lenses. Of these 59, 15
      individuals (25%) were optically ready and 44 individuals (75%) were not
      optically ready to deploy. Optical readiness is defined as having the correct
      type and number of optical devices. Of the 15 individuals (25%) who were
      optically ready, 13 (87%) had had a professional eye examination within 12
      months. Of the 44 individuals (75%) who were not optically ready, 36 (82%) had
      been examined within 1 year. Pearson's chi 2 test (chi 2 = 1.59, degrees of
      freedom = 3, significance = 0.66) indicated that there was no significant
      association between readiness and the date of the last examination. This study
      reveals that although personnel are having regular periodic professional eye
      examinations, optometry personnel, commanders, and deploying airmen must take a
      more active role in ensuring that our forces are vision ready.

PMID- 10920649
TI  - Injuries during Marine Corps officer basic training.
AB  - On average, about 25% of male and 50% of female enlisted recruits sustain one or
      more injuries during basic training. Because data on military officer populations
      are sparse, this study investigated injury incidence, injury rates, and modified
      duty days that occurred during Marine Corps officer basic training (6 weeks in
      length). Subjects were 480 officer candidates (including 30 females) undergoing
      training at Quantico, Virginia. The cumulative injury incidence (one or more
      injuries) was 60.8%, and the injury rate was 3.9 per 1,000 candidate hours of
      training. There were 378 primary injury encounters (first visit for a specific
      injury). The highest injury rates occurred during weeks 2, 3, and 6. Male injury
      categories with the highest rates (injuries per 100 trainees per 1,000 training
      hours) were blisters (0.68), sprains (0.58), and bone stress reactions (0.40).
      The highest injury rates in females were for bone stress reactions (1.35). On
      average, a total of 3.1% of training days constituted modified duty for each
      candidate. This study provides basic descriptive injury data for this unique
      military population that can assist in future planning for injury management and
      preventive interventional strategies.

PMID- 10920650
TI  - The application of the Landstuhl frame for air evacuation of patients with femur
      fractures.
AB  - The use of traction to transport patients with femur fractures is well accepted.
      This paper describes step-by-step the construction of a traction device suitable
      for use on military aircraft. This "Landstuhl frame" is easily constructed using
      materials readily available. It is quick and effective for the transportation of
      patients with lower extremity fractures.

PMID- 10920652
TI  - Activities of an ethics consultation service in a Tertiary Military Medical
      Center.
AB  - The Joint Commission on Accreditation of Healthcare Organizations requires
      hospitals to have a mechanism to address issues of medical ethics. Most
      hospitals, especially those in the military, have an ethics committee composed
      solely of members who serve as an additional duty. To enhance the ethics
      consultation service, the 59th Medical Wing created a position under the chief of
      the medical staff for a full-time, fellowship-trained, medical ethicist. After
      establishment of this position, the number of consultations increased, a
      systematic program for caregiver education was developed and delivered, and an
      organizational presence was achieved by instituting positions on the
      institutional review board, the executive committee of the medical staff, and the
      credentials committee. Issues in medical care are becoming increasingly
      complicated, due in large part to financial stresses and technological
      advancements. Ethics consultation can help prevent and resolve many of these
      problems. This report discusses the activities of the first year of a full-time
      ethicist in a tertiary military medical center.

PMID- 10920651
TI  - Do-not-resuscitate orders in the operating room: required reconsideration.
AB  - Advances in medical technology are giving health care providers the tools with
      which to keep patients alive for longer and longer periods of time. However, in
      our struggle to keep patients alive, we must not forget that the patient is the
      one who controls his or her own destiny. Advance directives and do-not
      resuscitate orders are becoming more commonplace as patients strive to make their
      wishes known to all who care for them. The use of such orders in the operating
      room has historically been a hotbed of controversy because it appears contrary to
      the necessity of surgery in the first place. Surgeons, anesthetists, operating
      room nurses, and others all have concerns regarding this issue, and they will be
      discussed here. The answer to the dilemma lies in a policy of "required
      reconsideration" to examine all factors of the do-not-resuscitate order and its
      applicability to the situation at hand.

PMID- 10920653
TI  - Responsibilities of a veterinary augmentation package in support of a contingency
      operation.
AB  - A veterinary augmentation package (VAP) was assigned to the 212th Medical
      Treatment Facility supporting Task Force Hawk outside Tirana, Albania, from April
      15 to July 4, 1999. The VAP's mission was to provide level I and II veterinary
      care, including emergency treatment, stabilization, and evacuation of military
      working dogs, and to ensure food safety and public health. This mission allowed
      the VAP to act as a force multiplier and to play an integral role in force
      protection. In the first 30 days of the operation, the VAP was confronted with
      animal issues concerning housing of the military working dogs, no access to
      emergency equipment, antiquated sets, kits, and outfits, and stray animal
      control. The food safety mission initially entailed inspections of operational
      rations and inspection of local sources for food procurement. Operational rations
      were replaced by A-rations, which required a central ration breakdown point to
      facilitate disbursement of food. The final step was to initiate the prime vendor
      program so that food was delivered directly to the dining facilities. Inspections
      of the port at which the food was arriving and a close association with
      preventive medicine personnel ensured a successful prime vendor operation.
      Veterinarians on future deployments should be prepared to supplement sets, kits,
      and outfits, pack an aid bag, and work closely with preventive medicine
      personnel, all while possibly living under the austere conditions of a combat
      zone.

PMID- 10920654
TI  - Smoking cessation and weight gain in the military.
AB  - Many studies of civilian populations have found a significant relationship
      between smoking cessation and weight gain. However, the effect of voluntary
      smoking cessation on weight for military personnel has not been studied. The
      present study evaluated 70 active duty military members (55 males and 15 females)
      who quit smoking after participating in an 8-week smoking cessation program. The
      results indicated that 88% of the participants gained weight and that the average
      weight gain was 6.4 lb (males, 5.5 lb; females, 9.8 lb). These results are
      particularly noteworthy because weight gain in military members may result in
      administrative actions for individuals exceeding weight standards. The authors
      recommend that military officials consider adopting a one-time temporary weight
      waiver for active duty military members who successfully quit smoking to help
      prevent any negative administrative consequences of post-cessation weight gain.

PMID- 10920655
TI  - Demographic, lifestyle, and psychosocial predictors of frequency of intoxication
      and other indicators as estimates of alcohol-related problems in Air Force basic
      military recruits.
AB  - This study examined demographic, lifestyle, and psychosocial variables to
      determine predictors of Air Force recruits who are likely to have alcohol-related
      problems. Subjects were all Air Force recruits (N = 32,144) entering basic
      training from August 1995 to September 1996. The dependent measures were self
      reported frequency of eight or more drinks per occasion, frequency of fighting
      while drinking, and typical frequency of alcohol consumption. Demographic
      analysis revealed that individuals high on any dependent variable were more
      likely to be male, older, non-Hispanic whites with some college. Lifestyle
      predictors included positive attitudes toward drug use and smoking status, with
      risk greater for females than males and for non-whites than non-Hispanic whites
      at the same smoking level. Psychosocial predictors included positive rebellious
      attitudes, decreased seatbelt use, and positive risk-taking attitudes, with risk
      greater for females than males at the same risk attitude level. These findings
      suggest that problem drinking falls into a broader category of risky problem
      behaviors.

PMID- 10920656
TI  - Laboratory testing for preeclampsia: result trends and screening recommendations.
AB  - To better direct screening for preeclampsia, we describe the result trends of the
      laboratory tests used in the workup of preeclampsia at our institution. The
      clinical characteristics of patients with abnormal test results are further
      detailed. The objective of the study is to recommend a laboratory screening
      regimen for preeclampsia based on the data. All patients who delivered at
      National Naval Medical Center from February to July 1996 who had blood urea
      nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, or
      uric acid determinations as part of a workup for preeclampsia were identified.
      Results are reported, and the clinical characteristics of patients with abnormal
      tests were obtained from the medical record. Abnormalities of uric acid and liver
      enzymes were few in our patient population (6% and 7%, respectively). The
      majority of patients with abnormal uric acid and liver function tests had the
      classic clinical symptoms of preeclampsia; therefore, the laboratory data added
      little to the clinical diagnosis. There was a high rate of renal test
      abnormalities, necessitating further investigation. We recommend omitting liver
      function and uric acid testing in the routine screening for preeclampsia. The
      high incidence of abnormal renal tests warrants continued use of this screening
      test and, more importantly, further investigation into the relationship between
      abnormal renal tests and disease course.

PMID- 10920657
TI  - Neisseria gonorrhoeae screening in pregnancy.
AB  - All patients undergoing prenatal care at the U.S Naval Hospital in Yokosuka,
      Japan, have a gonorrhea culture performed at their intake visit. The objective of
      this study was to determine the prevalence of Neisseria gonorrhoeae in this
      military population and to propose an effective antenatal screening strategy
      based on the data. A retrospective 10-month review of patient data was performed.
      In addition, the guidelines for antenatal N. gonorrhoeae screening by the
      American College of Obstetricians and Gynecologists, the Centers for Disease
      Control and Prevention, the U.S. Department of Health and Human Services, and the
      World Health Organization were reviewed. During the study period, none of the
      screened patients (N = 518) had a gonococcal infection. The screening program at
      this facility will be modified based on the low-risk nature of the pregnant
      population. Specifically, high-risk patients will be screened selectively in the
      third trimester.

PMID- 10920658
TI  - A review of intraosseous vascular access: current status and military
      application.
AB  - Austere far-forward battlefield environments present numerous obstacles in
      providing adequate medical care to the injured solidier. In addition to
      logistical constraints that limit the volume of isotonic crystalloid fluids
      available to resuscitate the injured soldier, hypotension, environmental and
      tactical conditions, and/or the presence of mass casualties can combine to lead
      to excessive delays in obtaining vascular access. For many years, intraosseous
      infusion has been a rapid, reliable method of achieving vascular access under
      emergency conditions in children. Although intraosseous infusion in adults was
      used extensively in the 1930s and 1940s, and a sternal puncture kit for bone
      marrow infusions was a common component of emergency medical supplies during
      World War II, only recently have there been discussions and experimental studies
      to evaluate intraosseous infusions in adult medical emergencies. With some
      medical elements of the U.S. military having recently been reissued intraosseous
      devices, we thought it timely to review the literature on this technique. This
      review discusses the efficacy and safety of intraosseous infusions of drugs and
      fluids, including insertion times and flow rates achieved. Although the intent is
      to evaluate the feasibility of the technique in the injured soldier, literature
      citations from studies in children, experimental animals, and human cadavers are
      included to support the statements made and to offer the reader the opportunity
      to read the original literature.

PMID- 10920660
TI  - Denial of pregnancy: a case study and literature review.
AB  - A case is presented of a young active duty woman who experienced nonpsychotic
      denial of pregnancy until she precipitously delivered a healthy full-term infant.
      Despite the lack of prenatal care and the requirement for neonatal resuscitation,
      the child has apparently developed normally. The woman had no ongoing psychiatric
      illness. She was able to make appropriate use of medical, nursing, and social
      work resources to function well with her child at home. The recent literature on
      denial of pregnancy is reviewed, and the clinical differences between
      nonpsychotic and psychotic denial of pregnancy are described. Clinical management
      and mobilization of social support structures can improve the chances of
      successful clinical outcomes in nonpsychotic denial of pregnancy.

PMID- 10920659
TI  - Bond strengths of two dental bonding systems.
AB  - A new bonding system named Kevloc has been introduced. It is based on
      acrylization of the metal surface with the goal of preventing the occurrence of a
      marginal gap between the metal and the resin. The purpose of this investigation
      was to determine the values of the shear bond strength achieved using the Kevloc
      technique on Ag-Pd (Auropal SE) and Co-Cr (Basil S) alloys and to compare them
      with those obtained with the OVS technique. The shear bond strengths were
      measured with the Smitz-Schulmayer shear test in a universal testing machine for
      polymer materials. A microscope image analyzer was used to measure the thickness
      of bonding layers and to reveal the possible occurrence of the marginal gap with
      both techniques. No marginal gap was detected with either technique. Kevloc
      provided better results than OVS only in a group of specimens tested after
      polymerization. Immersion in water and thermocycling reduced the initially high
      bond strength values of Kevloc specimens, whereas the bond strength values of OVS
      specimens remained unchanged regardless of which aging treatment was used.
      Microscopic examination did not reveal the existence of the marginal gap for
      either bonding system. According to the results obtained, it can be concluded
      that the Kevloc bonding system does not provide better shearing bond strength
      than the OVS bonding system.

PMID- 10920661
TI  - Hyperparathyroidism presenting as a nonunion of the femur: case report and review
      of the literature.

PMID- 10920662
TI  - [Diagnosis and therapy in diarrhea. Broken dam in the intestines].

PMID- 10920663
TI  - [What stops diarrhea? Often only trial and error help].

PMID- 10920664
TI  - [New successes with islet cell transplantation. Is insulin injection outmoded?.
      Interview by Dr. Bernhard Wiedemann].

PMID- 10920665
TI  - [Therapy of Alzheimer dementia. Current status and prospects].
AB  - In recent years, considerable progress has been made both in the diagnosis and
      treatment of dementia. Drugs have been developed which enhance cognitive
      performance in a large percentage of those afflicted, delay impairment of the
      ability to cope with the tasks of daily life, and avoid premature admission to a
      nursing home. In the practical medical care setting, however, these advantages
      are being utilized to only a limited extent, and this despite the fact that
      numerous therapeutic options are now available for the treatment of AD. New
      therapeutic approaches are aimed at inhibiting the pathological cleavage and
      extracellular and intracellular deposition of amyloid, preventing the toxic
      effects of amyloid accumulation around the neurons, and re-establishing
      intracellular transport deranged by the aggregation of neurofibrils. A further
      approach is the use of combinations of available substances with differing,
      possibly synergic, effects. Over and beyond this, treatment of AD in the
      "presymptomatic stage", or in the stage of only mild cognitive disturbance, is
      currently the subject of clinical trials.

PMID- 10920666
TI  - [Old myths hinder therapy. Memory disorders are not an expression of "normal"
      aging].

PMID- 10920667
TI  - [When no therapy helps the acne patient. Ask him if he works at McDonald's!].

PMID- 10920668
TI  - [Photoallergic contact eczema. Sunscreen + sun rays: not every skin tolerates
      that!].

PMID- 10920669
TI  - [Progressive renal failure. Why blood pressure must now be monitored].
AB  - Hypertension alone can lead to chronic nephrosclerosis and in addition promote
      the progressive worsening of renal function in various forms of renal disease,
      such as diabetic nephropathy, glomerular nephritis or interstitial nephritis.
      Thus, the treatment of chronic renal disease associated with reduced excretory
      function, requires not only general measures and a low-protein diet, but also
      intensified anti-hypertension treatment with diuretics or beta blockers. In a
      number of studies, progression or renal insufficiency has been shown to be slowed
      in particular through the use of angiotensin-converting enzyme inhibitors in
      patients with chronic renal failure.

PMID- 10920670
TI  - [Vasculitis syndrome. 2: Diagnosis and therapy].

PMID- 10920671
TI  - [Diagnostic quiz. First nosebleed, then the heart fails. Hereditary hemorrhagic
      telangiectasia (Osler-Weber-Rendu disease)].

PMID- 10920672
TI  - [Self control of blood coagulation values. The overwhelming majority of patients
      can be educated].

PMID- 10920673
TI  - [Chronic liver diseases. Hepatic encephalopathy too frequently overlooked?].

PMID- 10920674
TI  - [Early control of diabetic sequelae. Combined insulin treatment also in type 2].

PMID- 10920675
TI  - [Combined allergy treatment. Antihistaminics reduce steroid administration].

PMID- 10920676
TI  - [Benign prostatic hyperplasia. Finasteride controls progression of BPH].

PMID- 10920677
TI  - Infant mortality statistics from the 1998 period linked birth/infant death data
      set.
AB  - OBJECTIVES: This report presents 1998 period infant mortality statistics from the
      linked birth/infant death data set (linked file) by a variety of maternal and
      infant characteristics. METHODS: Descriptive tabulations of data are presented.
      RESULTS: In general, mortality rates were lowest for infants born to Cuban
      mothers (3.6 per 1,000), Central and South American (5.3), Asian or Pacific
      Islander (5.5), Mexican (5.6), and non-Hispanic white mothers (6.0), followed by
      Puerto Rican (7.8), American Indian (9.3), and black mothers (13.8). Infant
      mortality rates (IMRs) were higher for those infants whose mothers had no
      prenatal care, were teenagers, had 9-11 years of education, were unmarried, or
      smoked during pregnancy. Infant mortality was also higher for male infants,
      multiple births, and infants born preterm or at low birthweight. In 1998, 65
      percent of all infant deaths occurred to the 7.6 percent of infants born at low
      birthweight. The three leading causes of infant death--Congenital anomalies,
      Disorders relating to short gestation and unspecified low birthweight (low
      birthweight), and Sudden infant death syndrome (SIDS)--taken together accounted
      for 46 percent of all infant deaths in the United States in 1998. Cause-specific
      mortality rates varied considerably by race and Hispanic origin. For infants of
      black mothers, the IMR for low birthweight was nearly four times that for white
      mothers. For infants of American Indian mothers, the SIDS rate was 3.8 times that
      for Asian or Pacific Islander (API) mothers. For infants of Hispanic mothers, the
      SIDS rate was 44 percent lower than that for non-Hispanic white mothers.

PMID- 10920679
TI  - [The assessment of the nutritional status in patients with a resectable digestive
      tumor].
AB  - PROPOSAL: Tumoural disease leads to multifactorial cancerous cachexia. There are
      still few data available on the onset of this syndrome in operable patients,
      despite the repercussions on prognosis and the indication of nutritional support.
      GOAL: In this prospective study, we are considering the assessment of nutritional
      status in the light of the Chang protocol in with gastrointestinal tumours
      patients, as well as the possible differences depending on the location of the
      tumour, its progress, and the onset of septic complications. With this approach,
      we attempt to specify the indication of postoperative nutritional support.
      MATERIALS AND METHOD: The nutritional assessment protocol existing in the
      Department was reviewed as applied to 105 patients affected by oesophageal,
      gastric, pancreatic and colo-rectal cancer. This protocol included the ideal
      weight percentage (%IW), tricipital fold (TSF), arm muscle circumference (AMC),
      total albumin and lymphocytes (Chang protocol), as well as urea nitrogen. The
      database used was created in File Maker Pro running on a Macintosh computer and
      supported by the StatView programme for the statistical analysis of the results.
      RESULTS: There were 61 colo-rectal, 18 gastric, 17 oesophageal and 9 pancreatic
      carcinomas. There was some degree of malnutrition in 52.4% of patients but it was
      not severe in any case. An outstanding result is the percentage of ideal weight
      in excess of 100% on average in all of the groups, with little variation in the
      arm muscle circumference, as is the lower tricipital fold in the oesophageal and
      pancreatic cases. Albumin was significantly lower in gastric carcinoma cases and
      lymphocytes showed a correlation with the progress of the tumour and also with
      the onset of septic complications. The excretion of urea nitrogen did not reveal
      significant differences. In stages I and II, the patients were normally nourished
      or with marasmus, so that the only malnutrition found was of the kwashiorkor type
      and combined with stages III and IV. CONCLUSIONS: There is 52.4% of malnutrition
      in our surgically resectable digestive oncology patients using the Chang
      protocol, not susceptible of preoperative renourishment. This is found
      irregularly depending on the location and stage of the tumour. The total
      lymphocytes prior to surgery represented an independent variable which correlated
      with septic complications.

PMID- 10920678
TI  - [Polyamines in the gastrointestinal tract].
AB  - Polyamines are extremely important for cell growth, a fact that is reflected in
      the strict control of their synthesis and breakdown. In the small intestine, the
      polyamines play a fundamental role in all processes involving tissue
      regeneration, such as healing of stress-related ulcers, post-hepatectomy hepatic
      regeneration, adaptation syndrome after fasting and all processes with enterocyte
      hyperplasia or hypertrophy. In the gastrointestinal tract, there is a polyamine
      gradient in the villi-crypt cell axis and along the digestive tube, itself; the
      segments with greatest luminal content are the jejunum and the colon. Endogenous
      polyamine synthesis is stimulated by the diet and normal bacterial flora, which,
      in turn, regulate the amount and concentration of polyamines. Other hormonal and
      active peptide components (e.g. gastrin, epidermal growth factor, growth hormone)
      also have an influence on the pathway of polyamine synthesis. The interaction of
      these factors as related to the intestinal adaptive response is reviewed.

PMID- 10920680
TI  - [Energy requirements in the ICU. Calorimetry and expert opinion].
AB  - GOAL: To compare the method for calculating the energy requirements in critical
      patients as calculated by our computer software with those measured using
      calorimetry and using the recommendations of experts in nutritional support.
      REFERENCE POPULATION: 18 critical patients with mechanical ventilation and
      admitted to our ICU during 1998. ACTIONS TAKEN: Indirect calorimetry was carried
      out over a 24 hour period in critical patients with mechanical ventilation and
      their requirements were calculated using computer software. Ten of the
      measurements were placed on Internet web pages in order to receive the comments
      and recommendations of nutritional support experts. Those responses which fell
      into the range between 80% and 120% of the calorimetric measurement were
      considered correct. RESULTS: Calorimetric determinations were effected on 31
      occasions in 18 patients, with an average APACHE score of 19 +/- 3. The energy
      requirements measured by calorimetry were 34 +/- 3 kcal/kg/day with 0.34 +/- 16
      g/kg/day of nitrogen in urine, whereas the recommendations of the computer
      programme were 31 +/- 1 kcal/kg/day and 0.28 +/- 0.04 g/kg/day of nitrogen in
      urine, i.e. 92 +/- 8% of the former values. The responses by the experts to 10 of
      these measurements came very close to those of the programme, with 33 +/- 6
      kcal/kg/day and 0.29 +/- 0.06 gr/kg/day of nitrogen, with a percentage of correct
      responses of around 68%. CONCLUSIONS: The method for calculating the energy
      requirements used by our computer software constitutes around 92% of the
      calorimetric measurements in critical patients with mechanical ventilation and
      the responses are very similar to the average of the responses given by experts
      in nutritional support.

PMID- 10920681
TI  - [The nutritional status of the older population as a function of the
      institutionalization regimen].
AB  - BACKGROUND: Protein-energy malnutrition (PEM) is associated with an increase in
      morbi-mortality. It's prevalence in institutionalised elderly people is unknown
      in our environment. The aim of this study was to determine prevalence, typology
      and risk factors associated with PEM in institutionalised elderly people.
      SUBJECTS: 228 institutionalised elderly people, representative of the population
      in the town of Reus were studied. Among them 131 were resident geriatrics and 97
      long-stay hospital patients. METHODS: Weight, mid-arm circumference, body mass
      index, percentage of body fat, total cholesterol, total proteins, albumin,
      prealbumin and transferrin were determined. Predominantly caloric malnutrition
      was diagnosed if 2 or more anthropometric markers and less than 2 biochemical
      markers were affected. Predominantly protein malnutrition was diagnosed if 2 or
      more biochemical markers and less than 2 anthropometric markers were affected,
      and mixed-type PEM if 2 or more anthropometric markers and 2 or more biochemical
      markers coexist. RESULTS: The global prevalence of PEM was 26.7% (9.1% in the
      residencies and 50.5% in the hospitals). Predominantly Caloric, Protein and Mixed
      type malnutrition prevalence was 7.4%, 11% and 8.3% respectively. The 3 types of
      PEM were more prevalent among the hospitalised patients. Dementia was associated
      in 73.7% of 19 patients diagnosed of mixed PEM. CONCLUSIONS: A high prevalence of
      PEM was observed in the hospitalised patients. Hospitalisation was identified as
      an important risk factor in malnutrition, this could be explained by the diseases
      that make it necessary and the high prevalence of dementia observed in the
      hospitalised patients.

PMID- 10920682
TI  - [A comparison of 2 reference tables in nutritional anthropometric assessment].
AB  - OBJECTIVES: The valuation of nutritional state of an individual is necessary to
      performed a correct diagnostic approach and therapy in each case. This valuation
      can be performed by biochemical or anthropometric methods. In our country two
      tables of anthropometric values are used (Alastrue et al. and Frisancho et al.).
      The aim of our work was to compare the utility of both tables in the nutritional
      valuation of a urban and rural population of Valladolid. MATERIAL AND METHODS: A
      total of 110 patients were valued biochemically and anthropometrically,
      presenting 65.5% pathology tumoral, with a 61.41 +/- 16.73 year old half age.
      RESULTS: Tricipital pleat classified the patients in a similar way (agreement
      76.5%, kappa 0.68), however the muscular circumference of the arm didn't classify
      the patients in a same way (agreement 23%, kappa 0.02). in the correlation
      analysis among anthropometrics and biochemical parameters, positive correlations
      were detected between tricipital pleat and the index of corporal mass with the
      glucemia and cholesterol values. Positive correlations were also detected between
      the muscular circumference of the arm and urea and potassium levels. CONCLUSION:
      The anthropometric parameters are useful for the nutritional valuation of these
      patients but it is necessary to keep in mind the possible variations that can
      exist in function of the used tables. For it Would be useful that each
      geographical area and each group of pathologies even had its own table of
      percentiles in its normal population's function.

PMID- 10920684
TI  - [Japan Rheumatism Association should be carry out to reform forward to
      internationalization].

PMID- 10920683
TI  - [The quality of the care in parenteral nutrition: the benefits after the
      incorporation of a nutritional support team].
AB  - GOALS: The purpose of the study was to analyze the quality of the prescription
      and follow-up of the total parenteral nutrition (PNT) before and after the
      incorporation of a nutritional support team (NST). MATERIAL AND METHODS: A random
      sample of 96 patients was selected retrospectively, with 48 prior to the
      incorporation of the NST (the Non-NST group) and 48 after its incorporation (the
      NST group), to whom TPN was prescribed. The following points were assessed: 1.
      The existence of a minimum analytical and nutritional assessment, prior to the
      incorporation of TPN; 2. The follow-up of the same. RESULTS: The average duration
      of TPN per patient was 13.8 days without differences between the two groups.
      There is a written record of the weight and height in 15% and 10% of cases,
      respectively, in the Non-NST group as opposed to 100% and 99% in the NST group (p
      < 0.0001). Prior to the incorporation of the NST, the nutritional requirement was
      not verified in any patients (0%) as opposed to 97% afterwards. Statistically
      significant differences were detected in the measurement of albumin prior to the
      start of TPN (p < 0.01). During the analytical follow-up, statistically
      significant differences were detected in the measurement of: blood tests (p <
      0.05); basic biochemistry (p < 0.01); general biochemistry, magnesium, zinc, pre
      albumin, transferrin and nitrogen balance (p < 0.0001). In the TPN follow-up, the
      Non-NST group did not change any of the components contained in it (in terms of
      volume, macro or micronutrients) in 81% of patients, while 17% had one change and
      2% had 2 or more changes, as opposed to 27%, 42% and 31%, respectively in the NST
      group (p < 0.0001). There were no significant differences in metabolic
      complications between the two groups. CONCLUSIONS: The implementation of a
      nutritional support team in charge of the prescription and follow-up of TPN has
      notably improved the quality of these follow-up studies.

PMID- 10920685
TI  - [Assessment on intermittent intravenous cyclophosphamide pulse therapy in diffuse
      proliferative lupus nephritis].
AB  - OBJECTIVE: To determine whether intravenous cyclophosphamide pulse therapy (IVCY)
      is effective for treating patients with diffuse proliferative lupus nephritis
      (DPLN) who were 1) refractory to methylprednisolone pulse therapy (MP) or 2)
      could not be treated with MP because of severe diabetes or steroid induced
      psychosis. METHODS: Seven patients with biopsy proven DPLN were studied after
      informed consent. Five of them received IVCY after a failure to achieve renal
      remission with at least 2 cycles of MP therapy. Of the other 2 patients, one had
      severe diabetes and the other a history of steroid induced psychosis. Bolus
      therapy with cyclophosphamide (0.5 g/m2 body surface area) was given once a month
      for 6 consecutive months and then once every 3 months for a total treatment
      period of 1 year. All patients were given oral prednisone, 0.5 mg/kg per day. The
      prednisone dose was tapered to the minimal dose required for controlling the
      disease. After 1 year, the renal status of the patients were evaluated. RESULTS:
      At 1 year, 4 of the 7 patients achieved substantial improvement. Although the
      other 3 patients did not satisfy the definition of substantial improvement, none
      of them had progressive disease. Adverse events were mild and did not require any
      treatment, with 2 cases of leukocytopenia without fever or major infection. No
      cases of hemorrhagic cystitis or amenorrhea were observed. CONCLUSIONS: IVCY was
      1) effective in the treatment of DPLN which was refractory to MP and 2)
      relatively safe with minimal side effects.

PMID- 10920686
TI  - [A case of systemic lupus erythematosus with pulmonary hypertension].
AB  - A 15 year-old girl was admitted to the hospital because of fever, polyarthlargia,
      dry cough, dyspnea, butterfly rash and multiple oral aphthas. The diagnosis of
      systemic lupus erythematosus (SLE) was made based on renal disorders,
      pancytopenia, positive antinuclear antibody and positive for antibodies to double
      stranded DNA. On admission, she developed progressive dyspnea with highly active
      SLE. The patient was complicated with both pulmonary hypertension (PH) and
      interstitial pneumonitis (IP), judging from increased pulmonary sound by an
      auscultation, interstitial shadows especially at bilateral lower lung and
      enlarged shadow of right atrium in a chest rentgenogram, ground glass pattern of
      bilateral middle to lower lung in a chest computed tomographic scan, increased
      pulmonary artery pressure, 53 mmHg, by an ultrasound cardiograph (UCG).
      Combination of methylprednisolone pulse therapy, cyclosporin A and plasma
      exchanges was effectively administered, which resulted in improvement of disease
      activity of SLE, IP and PH. However, two months later, although disease activity
      of SLE was completely reduced, recurrence of PH by UCG and multiple pulmonary
      embolism (PE) which was observed by a chest rentgenogram and a pulmonary blood
      flow scintigraphy was further complicated. Administration of cyclophosphamide
      pulse therapy and warfarin therapy improved both PE and PH. The patient had PH at
      the different clinical course of SLE; 1) PH maybe induced by severe IP at the
      active phase of SLE and 2) PH brought about from multiple PE at the inactive
      phase of SLE. Thus, the case is thought to be suggestive of elucidating the
      pathogenesis of PH of several systemic autoimmune diseases including SLE.

PMID- 10920687
TI  - [A case of Sjogren's syndrome and systemic sclerosis complicated with acute
      pancreatitis].
AB  - We report a case of Sjogren's syndrome (SS) and systemic sclerosis (SSc)
      complicated with acute pancreatitis. A 51-year-old woman had been diagnosed as SS
      in 1973. She noticed Raynaud's phenomenon in 1977. In 1988, interstitial
      pneumonia (IP) was pointed out and she was treated with methylprednisolone (mPSL)
      pulse therapy. Prednisolone (PSL) was gradually tapered to 3-5 mg daily and she
      visited our outpatient clinic in 1995. On her first admission to our hospital in
      1996, she showed xerostomia, keratoconjunctivitis sicca, sclerotic skin changes
      of her distal extremities and face, thickening of her sublinguinal frenulum, and
      regurgitative esophagitis. She was positive with anti-SS-A and SS-B antibodies.
      She was diagnosed as SS and SSc. Radiographic and laboratory data also
      established the diagnosis of inactive IP, renal tubular acidosis (RTA) and
      chronic renal failure (CRF). In April 30th 1997, she was admitted to our hospital
      again with complaints of dyspnea, dysesthesia, epigastralgia and petechia. Active
      IP and mononeuritis multiplex were diagnosed, and petechia was considered to be
      associated with vasculopathy. Her serum amylase level was 891 mU/ml on admission
      and spontaneously increased to 2440 mU/ml on May 12th along with increase of
      fibrinogen degradation product, D-dimer and alpha 2 plasmin-plasmin inhibitor
      complex levels. Ultrasonography depicted swelling of her pancreatic head and the
      diagnosis of acute pancreatitis was made. She was treated with protease
      inhibitors and intravenous hyperalimentation for acute pancreatitis. mPSL pulse
      therapy (500 mg/day for 3 days) was instituted for IP and mononeuritis multiplex
      on May 22, followed by 50 mg of daily PSL. While IP and mononeuritis multiplex
      gradually improved by the high-dose steroid therapy, serum amylase level raised
      to more than 4293 mU/ml, suggesting the modification of pancreatitis by the
      treatment with steroid. Since she did not respond to the conservative therapy for
      acute pancreatitis, she was treated with plasmapheresis, which turned out to be
      very effective. However, she was suffered from fungal pneumonia and died of
      respiratory failure. As far as we know, only three cases of SS with acute
      pancreatitis have been reported so far. The immunopathological mechanisms of
      development of acute pancreatitis in our case, especially focusing on the
      significance of microvasculopathy and hypercoagulability, were discussed.

PMID- 10920689
TI  - [Rapidly progressed secondary amyloidosis in a patient with Still's disease with
      gamma-allele in his SAA 1 gene].
AB  - A fifteen-year-old boy was admitted to our hospital because of lower abdominal
      pain, watery diarrhea and mucobloody stool. Two years before admission, he was
      diagnosed to have Still's disease presenting with polyarthritis, sore throat,
      remittent fever and typical skin rash. He had been treated with non-steroidal
      anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although
      he was almost free of symptoms during the next two years, serum C-reactive
      protein (CRP) levels continued to be elevated moderately. He began to complain of
      lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody
      diarrhea in June. Laboratory data on admission showed an elevated level of serum
      CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum
      revealed the deposition of amyloid protein of AA type, which confirmed the
      diagnosis of secondary amyloidosis. The dose of prednisolone was increased and
      dimethyl sulfoxide per os or rectum was instituted, which improved his gastro
      intestinal symptoms to some extent. However, fever, arthritis and diarrhea
      recurred along with tapered prednisolone dosage. In addition to gastro-intestinal
      symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to
      reflect general deposition of amyloid in his body. He is now on immunosuppressive
      agent and high-dose prednisolone. Several studies report the higher frequency of
      gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA
      amyloidosis than in those without. In the patient presented here, molecular
      biological analysis revealed that his SAA 1 gene was composed of beta- and gamma
      allele. The presence of gamma-allele in his SAA 1 gene might be one of the
      factors that predisposed him for generalized deposition of amyloid protein in
      such a short period of time.

PMID- 10920690
TI  - [Rheumatoid vasculitis with multiple intestinal ulcerations: report of a case].
AB  - Rheumatoid vasculitis is a relatively uncommon complication of rheumatoid
      arthritis (RA). It shows wide variety of extra-articular features including skin
      and neurologic involvement, but rarely shows gastrointestinal involvement. We
      describe a 79-old-man of rheumatoid vasculitis manifesting as small bowel
      multiple ulcerations accompanied by perforation of the descending colon
      diverticulum. The patient was admitted to our hospital with rectal bleeding and
      severe anemia. He had had rheumatoid arthritis for more than 10 years with
      treatment of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose
      prednisone. Upper endoscopy or colonoscopy revealed no evidence of bleeding.
      Suddenly he developed cramping abdominal pain, and emergency operation was
      performed. Segments of the descending colon and small bowel were resected to
      reveal perforation of the descending diverticulum and severe multiple ulcer of
      small bowel. The pathological examination showed multiple ulcerations of the
      small intestine was caused by vasculitis.

PMID- 10920688
TI  - [A case of mixed connective tissue disease with lupus-like manifestations of the
      central nervous system, successfully treated with cyclophosphamide combined with
      prednisolone].
AB  - A 29-year-old woman experienced Raynaud's phenomenon, swelling of her fingers,
      eruptions on her face, and muscle weakness in 1990. She was diagnosed as having
      mixed connective tissue disease (MCTD) and was treated with prednisolone (PSL)
      for 3 years. Most of her complaints disappeared after the treatment. In March
      1997, she experienced fever, erythema, and lymphadenopathy. Although she was
      treated with PSL (20 mg/day) again, muscle weakness, mental disturbance, and
      recto-urinary disturbance appeared. When she was re-admitted to our hospital,
      increased levels of muscle-derived enzymes and positivity of anti-RNP antibody
      were found. High signal areas in her cerebrum were shown by magnetic resonance
      imaging, and slow and spike pattern was shown by electroencephalography.
      Hypoperfusion of the cerebral blood flow was suggested on single photon emission
      computed tomography. The number of mononuclear cells, amount of protein and level
      of interleukin-6 were found to be elevated in her cerebrospinal fluid (CSF). Her
      neurological manifestations were diagnosed as being due to MCTD, and showed
      characteristics similar to those of systemic lupus erythematosus. She was treated
      with PSL (60 mg/day) followed by steroid pulse therapy. Because the response to
      this treatment was partial, oral administration of cyclophosphamide (CPM) (100
      mg/day) was added. Muscle weakness and neurological abnormalities as well as
      abnormal laboratory findings gradually improved over the following two months. We
      conclude that the treatment with CPM combined with PSL may be useful, when
      neurological manifestations of MCTD are serious and resistant to conventional
      therapy.

PMID- 10920691
TI  - [What the education of rheumatology should be: present situation and the issue in
      Japan].

PMID- 10920692
TI  - [Mirthful laughter and patient with rheumatoid arthritis].

PMID- 10920693
TI  - [Medical science in ancient Egypt. Magic and reason in the concept of illness and
      therapeutic practice].

PMID- 10920694
TI  - ["Sound, unsound around the Sound". A congress report on health differences
      between Denmark and Sweden].
AB  - During the past 10 years, researchers on both sides of The Sound in the so-called
      Oresund region have worked together to analyze the causes of the observed
      differences in life expectancy between Denmark and Sweden. The region includes
      Copenhagen and North Zealand and the county of Scania in southern Sweden, with
      Malmo as its largest city. Both Denmark and Sweden held top rankings among OECD
      countries in 1970 regarding life expectancy at birth. In 1990 Denmark had fallen
      to a bottom ranking, while Sweden was still at the top. At a scientific meeting
      in Malmo on January 26-27, 2000, some 60 presentations were made concerning
      differences and similarities in health measures on the two sides of the sound
      which divides the two countries. On the Swedish side, life expectancy is 3-4
      years longer than on the Danish side. Paramount among explanations are higher
      mortality figures due to smoking and alcohol-related diseases on the Danish side,
      both in men and women (most pronounced). Minor contributions to the differences
      are suicides and traffic accidents. Historically, Denmark and Sweden have much in
      common. Until 1658, Scania, the Swedish county to the east of The Sound was part
      of Denmark. During the past 150 years rather impressive cultural differences have
      developed. Smoking prevalence and alcohol consumption are more than twice as high
      on the Danish side of the sound. In coming years, researchers, representatives
      for the health service systems and others will work together in order to prevent
      disease and promote health in the Oresund region. The conference was arranged by
      the Medicon Valley Academy, an EU-supported enterprise seeking to stimulate
      research and development within the health sector in the Oresund region (also
      known as Medicon Valley).

PMID- 10920695
TI  - [What is the special Nordic in medicine?].
AB  - Nordic health professionals often hear the term "the Nordic model" when visiting
      countries outside the Nordic ones. Such a Nordic model is most often related to
      selected aspects like the doctor-patient-relationship, the structures and
      functions of the Nordic health systems, and the Nordic establishments of
      independent, nationwide control systems dealing with research ethics and research
      honesty within the biomedical sciences. In the present essay the background for
      such a conception of special Nordic characteristics within medicine and health
      services is evaluated through an observation window. The conclusion is that the
      majority of individual components of the Nordic health sectors, including
      education and research, are by nature global, but that the weighting and the
      projection to clinical work and research shows decisive traits, especially
      related to patients' rights and ethics. On this background it seems legitimate to
      accept the surrounding world's impression of a special Nordic model.

PMID- 10920696
TI  - [Scandinavian guidelines for management of head injuries. Evidence-based
      management of minimal, mild and moderate head injuries].
AB  - The Scandinavian Neurotrauma Committee (SNC) was created by the Scandinavian
      Neurosurgical Society in order to develop evidence-based guidelines for improved
      care of neurotrauma patients. A MEDLINE search identified 475 papers dealing with
      the management of minimal, mild and moderate head injuries. Forty-two studies
      presenting Class II evidence on the initial management of such injuries were
      reviewed, and management guidelines were developed. Implementation of the Head
      Injury Severity Scale is advocated. Patients with Minimal injuries (no loss of
      consciousness [LOC], Glasgow Coma Scale [GCS] score 15) can be safely discharged.
      Routine early computerized tomography [CT] scan is recommended in cases with Mild
      injuries (history of LOC, GCS 14-15) and patients with normal scans may be
      discharged. CT scan and admission is mandatory in Moderate injuries (GCS 9-13).
      All patients with additional risk factors should be scanned and admitted. A flow
      chart for clinical decision making and a Head Injury Instruction card is
      introduced. The SNC suggests guidelines that should be safe and cost-effective
      for the initial management of minimal, mild and moderate head injuries.

PMID- 10920697
TI  - [Rapid increase of the use of PET in cancer investigation--but Sweden lags
      behind].
AB  - Glucose consumption in tissue can be measured using positron emission tomography
      (PET) and 18F-deoxyglucose (18FDG). Malignant tumors rely largely on anaerobic
      glycolysis and show very rapid glucose consumption, and can therefore be imaged
      using PET and 18FDG. PET has been shown to be useful in the evaluation of
      patients with e.g. lung cancer, colo-rectal cancer, malignant melanoma and
      malignant lymphoma, in terms of both diagnostic accuracy and cost-effectiveness.
      The clinical use of PET for workup of cancer patients is increasing rapidly in
      North America as well as in the European Union, but Sweden is lagging behind.

PMID- 10920698
TI  - [Chiral molecules--building stones of life].

PMID- 10920699
TI  - [Ophthalmologic image diagnostics].

PMID- 10920700
TI  - [Clinical nutrition in Danish hospitals. A questionnaire study among physicians
      and nurses].
AB  - Specific nutrition standards have now been developed by the Joint Commission on
      Accreditation of Healthcare Organizations (JCAHO). We investigated the use of
      clinical nutrition in Danish hospitals and compared it with the standards of
      JCAHO by doing a questionnaire-based investigation among doctors and nurses
      randomly selected in 40 hospitals. Overall, 857 (43.4%) responded to the
      questionnaire (doctors: 395, nurses: 462). Forty percent found it difficult to
      identify risk-patients, and 52% needed specific screening tools. Eighty-four
      percent found that a nutrition plan should be described in the patient record,
      but 39% found it difficult to set up an individual plan, and 79% expressed a need
      for specific guidelines. The use of clinical nutrition in Danish hospitals did
      not fulfill the standards for nutrition support according to the criteria
      established by JCAHO. Special efforts should be aimed at education, specific
      screening tools and introduction of guidelines in clinical nutrition.

PMID- 10920702
TI  - [Laryngeal spasm as a symptom of ventricular volvulus].
AB  - A male patient with laryngeal spasm as the only initial symptom of gastric
      volvulus is described. After gastric surgery the laryngeal spasms disappeared. A
      possible connection between laryngeal spasm and gastroesophageal acid reflux is
      discussed.

PMID- 10920701
TI  - [Prevalence of HIV and hepatitis B and C among drug addicts in the city of
      Copenhagen].
AB  - Blood samples were drawn from 291 drug users attending methadone clinics
      throughout 1997 and interviews performed about associated risk factors for
      seroconversion. The overall prevalence of HIV was 3.4%. Sixty-four percent tested
      positive for HBV and 75% for HCV. Almost all with a ten year history of drug use
      acquired one or more of the infections, including those who reported not to have
      injected. Among the sexually active 54% never used a condom and 14% of the
      injectors had shared needles within the last six months. Prevention measures
      contributing to the low prevalence of HIV had apparently no effect on
      transmission of hepatitis B and C. The findings call for more focus on hepatitis
      prevention including information, counselling, testing and vaccination.

PMID- 10920704
TI  - [Picture of the month. Allergic contact dermatitis].

PMID- 10920703
TI  - [Pregnancy associated osteoporosis].
AB  - A case of pregnancy associated osteoporosis in a 26 year-old woman's first
      pregnancy is described. Four months after delivery of a normal boy, the patient
      presented with back pain and fractures of the thoracic spine (Th 6, 7 and 9). The
      patient was treated with calcium and vitamin D. After three years the bone
      density was within normal range and had increased by 19.1% in the hip and 15.8%
      in the spine, respectively. Bone biopsy and extensive biochemical examinations
      including collagen analysis could not find any explanation for the observed
      fractures other than pregnancy.

PMID- 10920705
TI  - [Cochrane group for anesthesia].

PMID- 10920706
TI  - [Cooperation in the Sound region when it comes to developmental perspectives of
      prevention].

PMID- 10920708
TI  - [The accents of Meniere?].

PMID- 10920709
TI  - [Do we owe something?].

PMID- 10920707
TI  - [Magnetic resonance in choledocholithiasis--where are we actually?].

PMID- 10920710
TI  - [Is ARDS sometimes TRALS?].

PMID- 10920711
TI  - [Neglect].

PMID- 10920712
TI  - [Eye injuries].

PMID- 10920713
TI  - Leprosy--global situation.

PMID- 10920714
TI  - [On the constituents and biological activities of some Nepalese medicinal
      plants].
AB  - The chemical constituents of medicinal plants which have been used in Ayurvedic
      and Tibetan system of medicines in Nepal were examined. From 21 species
      consisting of 13 genera of the plants, 121 new compounds, whose structures are
      shown in Charts (1 to 13), were isolated mainly in our laboratory. Some of the
      compounds and their related ones showed several biological activities.

PMID- 10920715
TI  - [Antihypertensive effect of docosahexaenoic acid in stroke-prone spontaneously
      hypertensive rats].
AB  - Docosahexaenoic acid (DHA) is an n-3 unsaturated fatty acid derived from fish
      oils. The precise mechanisms of DHA actions are still obscure. Especially, the
      antihypertensive effect of DHA has not yet been elucidated. Stroke-prone
      spontaneously hypertensive rats (SHRSP) provide the best available model for
      essential hypertension and stroke. The present study was undertaken to elucidate
      the effects of long term administration of DHA on blood pressure and stroke
      related behavior in SHRSP. The blood pressure of DHA-treated SHRSP was lowered
      significantly as compared with that of non-treated SHRSP. DHA produced an
      ameliorative effect on the decreased passive avoidance response in SHRSP. DHA
      also improved the behavioral changes in spontaneous motor activity of SHRSP. DHA
      treated SHRSP produced a significant decrease in the levels of total cholesterol,
      low density lipoprotein, triglycerides, lipid peroxide, serum creatinine and
      blood urea nitrogen as compared with those in non-treated SHRSP. These findings
      indicate that the DHA-induced antihypertensive action may be associated with the
      amelioration of both serum lipid alteration and renal dysfunction in non-treated
      SHRSP. Moreover, DHA-treated SHRSP maintain the normal levels of acetylcholine
      and choline concentrations in the hippocampus and cerebral cortex. These findings
      demonstrated that DHA produced an ameliorative effect on cholinergic nerve
      dysfunction in SHRSP. The improved cholinergic nerve function induced by DHA
      might have an inhibitory effect on stroke-related behavior in SHRSP. The present
      study suggests that long term administration of DHA may suppress the development
      of hypertension and stroke-related behavioral changes in SHRSP.

PMID- 10920716
TI  - [Development of novel oxidation reactions using hypervalent iodine reagents and
      their application to total synthesis of biologically active natural products].
AB  - Recently, hypervalent Iodine (III) reagents have been used extensively in organic
      synthesis. In particular, phenyliodine (III) diacetate (PIDA) and phenyliodine
      (III) bis(trifluoroacetate) (PIFA) have received a great deal of attention due to
      low toxicity, ready availability, easy handling, and reactivities similar to that
      of heavy metal reagents or anodic oxidation. In contrast to the widely explored
      phenolic oxidation using PIDA or PIFA, reactions of phenol ethers with
      hypervalent iodine reagents have been limited and have yielded mostly iodonium
      salts. We found unexpectedly that the reaction of p-substituted phenol ethers
      with PIFA in the presence of some nucleophiles in polar and poorly nucleophilic
      solvents such as 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol
      caused a novel and straightforward nucleophilic substitution reaction on the
      aromatic ring via a cation radical intermediate [ArH+.]. Successful application
      of PIFA-induced umpolung of electron-rich aromatic ring reactivity allowed
      intramolecular cyclization reactions of phenol ethers leading to novel and
      efficient preparations of synthetically useful products such as biaryl compounds,
      quinone-imines, and sulfur-containing heterocycles. Using these methods, the
      first total synthesis of potent cytotoxic marine alkaloid, makaluvamine F was
      also achieved.

PMID- 10920717
TI  - [Thermolyses of N-allylides and N-vinylimino ylides: syntheses of mesomeric
      betaines involving back-donated 1,6-cyclization].
AB  - This review summarizes our studies on the development of the syntheses of
      mesomeric betaines by thermolysis of N-allylides and N-vinylimino ylides
      involving back-donated 1,6-cyclization. Furthermore interesting syntheses of
      heteropolycycles, indolizinoquinolizines via one step reaction are also reviewed.

PMID- 10920718
TI  - [Analysis of factors influencing the self-regulation of medication and
      construction of an educational program for patients with chronic hepatic
      diseases].
AB  - The purpose of this study is to construct an educational program for patients
      with chronic hepatic diseases to avoid self-regulation of medication. We have
      statistically analyzed the influencing factors of self-regulation from the
      following 3 viewpoints. First, in the investigation of the number of and the kind
      of prescribed medicines, it was found that the number of prescribed medicines
      increased sharply at the stage of Liver Cirrhosis b. Secondly, in the survey of
      patients' awareness of medication, it was found that self-regulation was
      influenced by lack of understanding the effects of medicines and the necessity of
      medication, and by lack of understanding the clinical conditions. Especially, at
      the stage of Liver Cirrhosis b, self-regulation was strongly influenced by lack
      of understanding the clinical conditions. Lastly, in the evaluation of patients'
      characteristics by pharmacists, self-regulation was also strongly influenced by
      the level of understanding the necessity of medication, understanding the
      clinical conditions, a patient-doctor relationship, and anxiety about side
      effects of medicines. Therefore we have constructed an educational program for
      patients from the viewpoint of medication. The information consists of two
      articles; one is the action mechanism of the medicine connected with the clinical
      conditions to help the patients understand the necessity of medication; the other
      is how to check the effect and adverse reaction of the medication by themselves
      to decrease the anxiety about side-effects. Consequently, the medication
      management and the consultation for inpatients with chronic hepatic diseases were
      standardized by incorporating the education with the information described above.

PMID- 10920720
TI  - A treatise on water.

PMID- 10920719
TI  - [Preparation and clinical evaluation of orally-disintegrating clonidine
      hydrochloride tablets for preanesthetic medication].
AB  - Orally-disintegrating tablets of clonidine hydrochloride, an alpha 2-adrenergic
      agonist, were prepared by the method of drying an aqueous suspension. The
      suspension was prepared using powdered lactose, and the composition ratio was 2:1
      (powdered lactose: 0.048% clonidine hydrochloride solution). The suspension was
      dried under 4 +/- 1 degrees C (72 +/- 15% R.H.). We obtained tablets containing
      clonidine hydrochloride (40 micrograms/tablet). Physical properties of the
      tablets were as follows: hardness was 4.0 kgf, and disintegration time was 41.7 s
      (in vitro). In the clinical use, 8 patients, aged 1-2 year and weighing 9-11 kg,
      received approximately 4 micrograms/kg body weight as clonidine hydrochloride.
      The tablet was administered 90 min before entering the operating room. All
      patients were willing to accept the tablet. The quality of separation from
      parents, sedation and a mask acceptance were excellent on all patients. These
      results suggest that the orally-disintegrating tablet of clonidine hydrochloride
      was useful in a clinical situation for the preanesthetic medication of pediatric
      patients aged 1-2 year.

PMID- 10920721
TI  - What's in a name?

PMID- 10920722
TI  - HIV infection and risk behaviours in young gay and bisexual men.

PMID- 10920723
TI  - Different centuries, same old story.

PMID- 10920724
TI  - Plastic bread-bag clips: the saga continues.

PMID- 10920725
TI  - Plastic bread-bag clips: the saga continues.

PMID- 10920727
TI  - Changes in the treatment and outcomes of acute myocardial infarction in Quebec,
      1988-1995.
AB  - BACKGROUND: Few studies have reported population-based information on the
      treatment trends and outcomes of patients who have had an acute myocardial
      infarction (AMI). We therefore examined patterns of care and outcomes for AMI
      patients in Quebec, Canada, between 1988 and 1995. METHODS: Longitudinal data
      files of hospital admissions in Quebec (Med-Echo database) and inpatient and
      outpatient services (Regie de l'Assurance Maladie du Quebec database) were used
      to construct cohorts of all AMI patients in the province between 1988 and 1995.
      Temporal trends in the use of cardiac procedures after an AMI, discharge
      prescriptions and mortality rates were examined. RESULTS: Between 1988 and 1995
      the age- and sex-adjusted rates of AMI in the Quebec population declined (148 per
      100,000 in 1988 to 137 per 100,000 in 1995). The use of intensive cardiac
      procedures increased in the same period; the 1-year cumulative incidence rate of
      catheterization increased from 28% in 1988 to 31% in 1994, that of angioplasty
      rose from 8% to 15% and that of coronary artery bypass surgery from 6% to 8%.
      Prescriptions for ASA, beta-blockers, lipid-lowering agents and angiotensin
      converting enzyme inhibitors increased, and prescriptions for nitrates and
      calcium antagonists decreased. These temporal changes were paralleled by a
      decrease in mortality rates post-AMI. All-cause 1-year cumulative incidence
      mortality rates decreased from 23% in 1988 to 19% in 1994. INTERPRETATION: The
      decrease in AMI-related mortality in Quebec between 1988 and 1995 may be linked
      to changes in treatment strategies (i.e., increased use of cardiac surgical
      procedures and medications shown to increase survival).

PMID- 10920728
TI  - Homocysteine: to screen and treat or to wait and see?

PMID- 10920726
TI  - Preventive health care, 2000 update: screening and management of
      hyperhomocysteinemia for the prevention of coronary artery disease events. The
      Canadian Task Force on Preventive Health Care.
AB  - OBJECTIVE: To establish guidelines for the screening and treatment of
      hyperhomocysteinemia in the investigation and management of coronary artery
      disease (CAD). OPTIONS: Measurement of plasma total homocysteine (tHcy) levels in
      the fasting state or 4-6 hours after oral methionine load; vitamin
      supplementation with folic acid and vitamins B6 and B12; adherence to the
      recommended daily allowance of dietary sources of folate and vitamins B6 and B12.
      OUTCOMES: This article reviews the available evidence on the association between
      plasma tHcy levels and CAD and the effect of lowering tHcy levels through vitamin
      supplementation or dietary intake. EVIDENCE: MEDLINE was searched for relevant
      English-language articles published from January 1966 to June 1999; also reviewed
      were additional articles identified from the bibliographies. BENEFITS, HARMS AND
      COSTS: Cardiovascular disease is the leading cause of death in Canada.
      Homocysteine, generated in the metabolism of methionine, may have a role in the
      development of cardiovascular disease. The prevalence of hyperhomocysteinemia in
      the general population is between 5% and 10% and may be as high as 30%-40% in the
      elderly population. If population-based studies are correct, tHcy may be
      responsible for up to 10% of CAD events and thus may represent an important and
      potentially modifiable risk factor for cardiovascular disease. Laboratory testing
      for tHcy is currently restricted to research centres, and costs range from $30 to
      $50 per person. Newer, less costly techniques have been developed and should
      become readily available with time. VALUES: The strength of evidence was
      evaluated using the methods of the Canadian Task Force on Preventive Health Care.
      RECOMMENDATIONS: Although there is insufficient evidence to recommend the
      screening or management of hyperhomocysteinemia at present (grade C
      recommendation), adherence to recommended daily allowance of dietary sources of
      folate and vitamins B12 and B6 should be encouraged. If elevated tHcy levels are
      discovered, vitamin deficiency should be ruled out to allow specific treatment
      and prevention of complications, such as neurological sequelae due to vitamin B12
      deficiency. Experts in the field advocate treatment of elevated tHcy levels in
      high-risk people, such as those with a personal or family history of premature
      atherosclerosis or a predisposition to develop hyperhomocysteinemia. Definitive
      guidelines for the management of hyperhomocysteinemia await the completion of
      randomized trials to establish the effect of vitamin supplementation on CAD
      events. VALIDATION: The findings of this analysis were reviewed through an
      iterative process by the members of the Canadian Task Force on Preventive Health
      Care. SPONSORS: The Canadian Task Force on Preventive Health Care is funded
      through a partnership between the Provincial and Territorial Ministries of Health
      and Health Canada.

PMID- 10920729
TI  - Sudden neck movement and cervical artery dissection. The Canadian Stroke
      Consortium.

PMID- 10920730
TI  - Acute myocardial infarction in Canada: improvement with time.

PMID- 10920731
TI  - Who wants to pay for health care?

PMID- 10920734
TI  - Expansion of gambling in Canada: implications for health and social policy.
AB  - Canada experienced a dramatic increase in legalized gambling in the 1990s,
      primarily because of governments' need to increase revenue without additional
      taxation. This article examines gambling from a public health perspective. The
      major public health issues include gambling addiction, family dysfunction and
      gambling by youth. Debates have emerged about the health, social and economic
      costs and benefits of gambling. Stakeholder and social policy groups have
      expressed concern about the impact of expanded gambling on the quality of life of
      individuals, families and communities. Epidemiological studies show that the
      prevalence of gambling in the general adult population is low but increasing. Of
      particular concern is the high though steady prevalence of gambling among youth.
      New technologies have been linked to gambling-related problems such as addiction
      to gambling by video lottery terminals. Gambling by means of the Internet
      represents another emerging issue. The article concludes with recommendations for
      health and social policy related to gambling. These recommendations incorporate a
      broad public health approach to create a strong research program and to balance
      risks and benefits.

PMID- 10920733
TI  - Choosing a first-line drug in the management of elevated blood pressure: what is
      the evidence? 1: Thiazide diuretics.
AB  - Elevated blood pressure is associated with an increased risk of cardiovascular
      illness and death. Efforts to reduce that risk have led to recommendations for a
      wide array of nondrug and drug therapies. Choosing the optimal first-line drug
      for hypertensive patients should address a hierarchy of treatment goals: decrease
      in morbidity and mortality associated with hypertension, decrease in blood
      pressure, lack of effect on patients' quality of life, dosing convenience and low
      cost. This article examines the evidence for thiazide diuretics as a class of
      first-line antihypertensive drugs in light of these treatment goals. The evidence
      indicates that low-dose thiazides are preferable to high-dose thiazides and that
      low-dose thiazides are better than or equivalent to other antihypertensive drugs
      for each of the goals of therapy.

PMID- 10920732
TI  - Emerging relations between infectious diseases and coronary artery disease and
      atherosclerosis.
AB  - Cardiovascular disease is the leading cause of death in developed countries. The
      cause is multifactorial. A substantial proportion of patients with coronary
      artery disease (CAD) do not have traditional risk factors. Infectious diseases
      may play a role in these cases, or they may intensify the effect of other risk
      factors. The association of CAD and Chlamydia pneumoniae infection is firmly
      established, but causality is yet to be proven. The link with other infectious
      agents or conditions, such as cytomegalovirus, herpes simplex virus, Helicobacter
      pylori and periodontitis, is more controversial. Cytomegalovirus infection is
      more strongly linked than native CAD to coronary artery restenosis after
      angioplasty and to accelerated CAD after cardiac transplantation. However, new
      data on this topic are appearing in the literature almost every month. The
      potential for novel therapeutic management of cardiovascular disease and stroke
      is great if infection is proven to cause or accelerate CAD or atherosclerosis.
      However, physicians should not "jump the gun" and start using antibiotic therapy
      prematurely for CAD. The results of large randomized clinical trials in progress
      will help establish causality and the benefits of antimicrobial therapy in CAD.

PMID- 10920735
TI  - Canadians suing over cigarette-related fires.

PMID- 10920736
TI  - Alberta allows midwives to practise in hospitals if patients pay.

PMID- 10920737
TI  - Ottawa seeks source of medical marijuana.

PMID- 10920738
TI  - Combating car accidents by examining the causes.

PMID- 10920740
TI  - Aging population means more cancer cases.

PMID- 10920739
TI  - Natural health products get own directorate at Health Canada.

PMID- 10920741
TI  - Health Canada undergoes a shakeup.

PMID- 10920742
TI  - Treating obsessive-compulsive and tic disorders.

PMID- 10920743
TI  - Making our water safe to drink.

PMID- 10920744
TI  - Olanzapine (Zyprexa): suspected serious reactions.

PMID- 10920745
TI  - Sildenafil (Viagra): cardiac risks.

PMID- 10920746
TI  - Evaluating policy and practice: what are the effects of early hospital discharge
      after childbirth?

PMID- 10920747
TI  - Medical research in Australia: into the new millennium.

PMID- 10920748
TI  - ARDS: nothing new?

PMID- 10920749
TI  - Cancer in the family: risks and management.

PMID- 10920750
TI  - Early discharge and postnatal depression: a prospective cohort study.
AB  - OBJECTIVES: To determine whether women discharged from hospital < or = 72 hours
      after childbirth (early discharge) were at greater risk of developing symptoms of
      postnatal depression during the following six months than those discharged later
      (late discharge), their reasons for early discharge and their level of postnatal
      support. DESIGN AND SETTING: Population-based, prospective cohort study with
      questionnaires at Day 4, and at 8, 16 and 24 weeks postpartum, conducted at all
      birth sites in the Australian Capital Territory (ACT). PARTICIPANTS: Women
      resident in the ACT giving birth to a live baby from March to October 1997. MAIN
      OUTCOME MEASURE: A score > 12 on the Edinburgh Postnatal Depression Scale (EPDS).
      RESULTS: 1295 (70%) women consented to participate; 1193 (92%) were retained in
      the study to 24 weeks and, of these, 1182 returned all four questionnaires. Of
      the 1266 women for whom length-of-stay data were available, 467 (37%) were
      discharged early and 799 (63%) were discharged late. There were no significant
      differences between the proportion of women discharged early who ever scored > 12
      on the EPDS during the six postpartum months and those discharged late (17% v.
      20%), even after controlling for other risk factors (adjusted OR, 0.67; 95% CI,
      0.44-1.01). Of women discharged early, 93% had at least one postnatal visit at
      home from a midwife and 81% were "very satisfied" with the care provided. Most
      women (96%) reported they had someone to help in practical ways. CONCLUSIONS:
      Women discharged early after childbirth do not have an increased risk of
      developing symptoms of postnatal depression during the following six months.

PMID- 10920751
TI  - Management of gestational diabetes with a conservative insulin protocol.
AB  - OBJECTIVE: To investigate whether 2-hour postprandial blood glucose levels up to
      8.0 mmol/L affect maternal or neonatal outcomes in pregnancies complicated by
      gestational diabetes mellitus (GDM). DESIGN: Retrospective analysis of data
      collated by the Victorian Perinatal Data Collection Unit. PATIENTS: 394 GDM women
      and 394 control women matched for age and country of birth who gave birth at a
      university teaching hospital, 1991-1997. MAIN OUTCOME MEASURES: Maternal-
      hypertension/pre-eclampsia, obstetric intervention, gestation at delivery, length
      of hospital stay; neonatal--Apgar scores, time to establish respiration,
      birthweight, macrosomia, large or small for gestational age (LGA or SGA),
      fetopelvic disproportion, jaundice, hypoglycaemia. RESULTS: For most outcome
      measures there were no statistically significant differences between the GDM and
      control groups. However, in the GDM group, gestation was shorter, hospital stays
      longer and delivery interventions more common. CONCLUSION: Our study suggests
      that maternal and neonatal outcomes in GDM women are comparable with those of
      women without GDM when 2-hour postprandial glucose levels of up to 8mmol/L are
      maintained. This is 1.0 mmol/L higher than the current Australian Diabetes in
      Pregnancy Society recommendation.

PMID- 10920752
TI  - Making a difference to socioeconomic determinants of health in Australia: a
      research and development strategy.
AB  - Disparities in health across the socioeconomic spectrum are now recognised
      worldwide and demand policy action. Pathways from social disadvantage to health
      outcomes are poorly understood, and reducing social disadvantage poses
      crosscutting political, moral and methodological issues. The Health Inequalities
      Research Collaboration, an initiative of the Commonwealth Department of Health
      and Aged Care, is establishing a research and development process to support
      departmental efforts to reduce health inequalities. The collaboration is building
      research networks in child development, community resources and primary
      healthcare. Policy action needs to extend beyond the health portfolio and the
      role of government. Broad strategies are required, as is research to fearlessly
      evaluate the health effects of government policy, economic activity and cultural
      change. The Canadian Institute for Advanced Research is a model for national
      research of the kind needed in Australia.

PMID- 10920753
TI  - Determining the validity of advance directives.
AB  - We examine the ethical principles underpinning advance directives (ADs) and the
      legal duties of doctors in determining their validity. A physician attending an
      incompetent patient with an acute life-threatening illness, and an AD refusing
      treatment, should ensure that the AD is legally valid before making the treatment
      decision. Treatment against a patient's wishes, as expressed in a valid AD,
      compromises patient autonomy and may constitute battery. Conversely, withholding
      treatment in accordance with an AD that is not legally valid risks substantial
      harm to the patient and may constitute breach of the duty of care and negligence.
      Legally valid directives should be respected. If an AD is not legally valid, the
      patient should be treated in his or her best interests. If uncertain, the
      physician should treat according to the patient's best interests while seeking
      legal advice.

PMID- 10920754
TI  - Active and passive cigarette smoking and breast cancer: is a real risk emerging?

PMID- 10920755
TI  - Back pain in an elderly man--more than just a fall.

PMID- 10920756
TI  - Neurology. 4: Multiple sclerosis.
AB  - Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the
      central nervous system (CNS) and a common cause of disability in young adults; it
      is most likely an autoimmune disease. Typically, MS initially follows a relapsing
      remitting course, but most patients eventually develop secondary progressive MS,
      where there is progressive deterioration without relapses or remissions; in some
      patients, MS has a primary progressive course. The diagnosis of MS requires
      evidence of CNS lesions disseminated in time and place, as well as the exclusion
      of other likely causes of these lesions; the clinical history, neurological
      examination and investigations, such as magnetic resonance imaging of the brain
      and spinal cord, all have key roles in the diagnosis. Education and counselling
      of the patient and family members are essential for good patient management.
      Moderate to severe attacks of MS are best treated with intravenous infusions of
      high-dose methylprednisolone. Interferon beta reduces the frequency of attacks
      and the progression of disability in relapsing-remitting MS. Symptomatic therapy
      is important in the management of spasticity, pain, urinary problems and the
      other symptoms or complications of MS.

PMID- 10920757
TI  - Concordance between use of proton pump inhibitors and prescribing guidelines.

PMID- 10920758
TI  - Disseminated tuberculosis: still a diagnostic challenge.

PMID- 10920759
TI  - Unusual blow-out fractures of the orbit.

PMID- 10920760
TI  - Prostate cancer in Victoria in 1993: patterns of reported management.

PMID- 10920761
TI  - Mobile Australians: a moving target for epidemiologists.

PMID- 10920762
TI  - Antibiotic use in livestock.

PMID- 10920763
TI  - The invisible epidemic.

PMID- 10920764
TI  - Speaking up for science.

PMID- 10920765
TI  - A taste of weightlessness.

PMID- 10920766
TI  - The ascent of scent.

PMID- 10920767
TI  - Xenotransplantation. Pork progress.

PMID- 10920768
TI  - The fate of life in the universe.

PMID- 10920769
TI  - Vision: a window on consciousness.

PMID- 10920770
TI  - Need for care and consideration in disposal of vet practice waste.

PMID- 10920771
TI  - Equine piroplasmosis visits Australia in 2000.

PMID- 10920772
TI  - Penstrep clarification.

PMID- 10920773
TI  - Extracapsular stabilisation.

PMID- 10920774
TI  - Intra-articular replacement.

PMID- 10920776
TI  - Distraction osteogenesis to treat premature distal radial growth plate closure in
      a dog.
AB  - A 4-month-old Labrador was presented for forelimb lameness and elbow pain.
      Radiography revealed asymmetric premature closure of the distal radial physis
      resulting in humeroradial and humero-ulnar subluxation. A four-ring circular
      external fixator applied to the antebrachium was used to perform distraction
      osteogenesis. After a 4 day latency period, varying rates of linear distraction
      were used to lengthen the radius by 50% of its original length, which is
      significantly longer than has been previously reported. By 69 days after
      performing the radial osteotomy, the distraction callus had achieved clinical
      union and the fixator was removed. One year postoperatively, mild lameness was
      present after exercise and minimal elbow osteo-arthritis was evident
      radiographically. Complications observed included pin tract drainage, transient
      carpal contracture and radio-ulnar synostosis.

PMID- 10920775
TI  - Tibial plateau levelling.

PMID- 10920777
TI  - Aero-allergens in canine atopic dermatitis in southeastern Australia based on
      1000 intradermal skin tests.
AB  - OBJECTIVE: To determine the most relevant aero-allergens involved in canine
      atopic dermatitis in southeastern Australia and provide information about these
      aero-allergens to the general practitioner. PROCEDURE: Dogs presented to the
      Animal Skin & Allergy Clinic with history and clinical signs of atopic dermatitis
      were injected intradermally with 38 different allergens and negative and positive
      control. Intradermal skin tests in 1000 dogs were retrospectively evaluated.
      RESULTS: One third of all patients reacted to the house dust mite
      Dermatophagoides farinae. Allergens reacting in more than 15% of the patients
      were wheat (Triticum aestivum), sweet vernal (Anthoxanthum odoratum), English
      couch (Agropyron repens), yellow dock (Rumex crispus), Mexican tea (Chenopodium
      ambrosioides), plantain (Plantago lanceolata), melaleuca (Melaleuca
      quinquenervia) and peppercorn (Schimus spp). CONCLUSION: House dust mites are the
      most common allergens in canine atopic dermatitis in southeastern Australia and D
      farinae is involved most frequently. However, a number of grass, weed and tree
      pollens also are involved regularly.

PMID- 10920778
TI  - West Nile virus finds a new ecological niche in Queens, New York.

PMID- 10920779
TI  - Acute cortisol responses and wound healing in lambs after ring castration plus
      docking with or without application of a castration clamp to the scrotum.
AB  - OBJECTIVE: To test whether the cortisol response to ring castration plus docking
      is reduced by additional application of a castration clamp across the full width
      of the scrotum distal to the ring. DESIGN: A physiological study with controls.
      PROCEDURE: Lambs, 3 to 6 weeks of age, were castrated using a ring or ring plus
      castration clamp applied for 6 or 10 s and docked using a ring. Blood samples
      were taken before and regularly for about 4 h after treatment and analysed for
      plasma cortisol concentrations. The healing of the scrotal wounds was monitored
      for 6 weeks after castration. RESULTS: The plasma cortisol concentrations were
      lower only at 60 min after treatment in lambs castrated with a clamp placed on
      the scrotum for 10 s after ring castration and docking than in lambs castrated
      and docked by ring alone. Scrotal wounds healed more quickly after ring plus
      clamp than after ring only castration. CONCLUSIONS: The castration clamp had at
      most a marginal effect on the cortisol response to ring castration and docking of
      3- to 6-week-old lambs, but it did seem to improve the rate of healing.

PMID- 10920780
TI  - Platinum pharmacokinetics in sulphur-crested cockatoos (Cacatua galerita)
      following single-dose cisplatin infusion.
AB  - OBJECTIVE: To determine the pharmacokinetics of platinum (Pt) in cockatoos.
      DESIGN: A pharmacokinetic study of Pt, following a single i.v. infusion of
      cisplatin, was done in six healthy sulphur-crested cockatoos (Cacatua galerita).
      PROCEDURE: Birds were hydrated for 1 h before and 2 h after a 1-h cisplatin
      infusion (1 mg/kg, i.v.). Serial blood samples were collected for 96 h after
      initiation of the infusion and urine was collected for 2 h during the hydration
      period after cisplatin administration. Tissue samples from 10 organs were
      obtained at necropsy, 96 h after cisplatin infusion. Total Pt and filterable Pt
      in plasma, urinary Pt and tissue Pt concentrations were assayed by inductively
      coupled plasma-mass spectrometry. A noncompartmental pharmacokinetic analysis was
      performed on the plasma and urine data. RESULTS: For total Pt and filterable Pt,
      the respective mean systemic clearances were 0.373 and 0.699 L/kg hourly, the
      steady state volumes of distribution were 4.19 and 0.356 L/kg, and the mean
      residence times were 111 and 0.512 h. Total plasma Pt displayed a bi-exponential
      decay profile with average half-lives of 0.398 and 79.0 h, while filterable Pt
      had a monoexponential decay with mean half-life of 0.413 h. The renal clearance
      during the 2-h postinfusion period was 0.167 L/kg hourly. The kidneys had the
      highest Pt accumulation (4.54 micrograms/g DM). CONCLUSIONS AND CLINICAL
      RELEVANCE: Cisplatin infusion in cockatoos was well tolerated and Pt plasma
      concentrations were similar to those measured during treatment of solid tumours
      in human patients. Despite anatomical, physiological and biochemical differences
      among animal species, the pharmacokinetic disposition of Pt in the cockatoo
      shares some features with the kinetics reported previously in rodents, dogs and
      human beings.

PMID- 10920781
TI  - Congenital caudal vertebral malformations in the alpaca (Lama pacos).
AB  - OBJECTIVE: To assess radiologically the caudal vertebrae of a male alpaca with an
      abnormal tail, and nine of his offspring. PROCEDURE: Right lateral and
      ventrodorsal radiographs were taken of the caudal vertebrae. RESULTS: The caudal
      vertebral abnormalities in these alpacas included vertebral subluxation,
      hemivertebrae, wedge hemivertebrae and block vertebrae. CONCLUSION: These
      malformations in offspring of one sire suggest a hereditary basis for congenital
      caudal vertebral malformations in the alpaca.

PMID- 10920782
TI  - Plasma and urinary trypsinogen activation peptide in healthy dogs, dogs with
      pancreatitis and dogs with other systemic diseases.
AB  - OBJECTIVE: To determine the specificity and sensitivity of plasma and urinary
      trypsinogen activation peptide (TAP) concentrations in diagnosing pancreatitis in
      dogs. DESIGN: Retrospective analysis of clinical cases. PROCEDURE: Dogs were
      classified into three groups: healthy animals, dogs with confirmed pancreatitis
      and dogs with nonpancreatic disease, which clinically or biochemically resembled
      pancreatitis. This last group was further subdivided into dogs with renal and
      those with nonrenal disease. The plasma and urinary TAP concentration was
      determined by a competitive enzyme immunoassay. Clinical cases additionally had
      serum trypsin-like immunoreactivity concentration measured, as well as
      radiography and ultrasound of the abdomen and further diagnostic procedures.
      Nonparametric analysis of variance (Kruskal-Wallis test) was performed using
      Statistix 4.0 program. RESULTS: There was a wide range of urinary TAP
      concentration in healthy dogs (mean 52.30 nmol/L, standard deviation 55.25) that
      made interpretation of urinary TAP concentrations difficult in the other groups.
      There was a narrow reference range for plasma TAP (mean 2.67 nmol/L, standard
      deviation 0.93). Plasma and urinary TAP concentrations, as well as urinary TAP to
      creatinine ratio, were all increased in dogs that died with necrotising
      pancreatitis. Values were not increased in mild, interstitial pancreatitis.
      Increased plasma TAP concentrations were also present in dogs with severe renal
      disease. CONCLUSION: Plasma TAP concentration is a good prognostic indicator in
      naturally occurring pancreatitis in dogs. The failure of TAP to increase in mild
      pancreatitis, and the increase present in severe renal disease, suggests its
      measurement has limited application as a sole diagnostic tool for canine
      pancreatitis. Further investigations are required in order to explain the large
      variability of urinary TAP concentration and the presence of circulating TAP in
      healthy dogs.

PMID- 10920783
TI  - ELISA for anti-MPB70: an option for the diagnosis of goat tuberculosis caused by
      Mycobacterium bovis.

PMID- 10920784
TI  - Factors affecting plasma bilirubin in preterm infants ventilated for respiratory
      distress syndrome.
AB  - OBJECTIVE: To evaluate the contribution of various factors to plasma bilirubin
      level in preterm infants with a birth weight of < 1500 gm in need of mechanical
      ventilation for respiratory distress syndrome (RDS) during their first week of
      life. METHODOLOGY: A total of 50 very low birth weight (< 1500 gm) preterm
      infants consecutively admitted to the neonatal intensive care unit were studied.
      Plasma bilirubin levels were determined every 8 hours for the first week of life.
      Data relating to daily body weight, daily fluid intake, age at onset of gavage
      feeds, daily caloric intake, and grade of intraventricular hemorrhage (IVH) were
      collected. Data relating to mechanical ventilation were collected every 4 hours
      as follows: fractional inspired O2, arterial PO2, arterial PCO2, and mean airway
      pressure. An arterial/alveolar PO2 ratio and a corrected oxygenation index were
      computed for the first 2 days of life. A bilirubin index (BI), defined as the
      ratio of peak plasma bilirubin level to birth weight1/3, was used to study the
      association between bilirubin and the above variables. A BI was also used as a
      criterion for starting and discontinuing phototherapy. Multiple linear regression
      analysis was used to model BI. RESULTS: IVH (p < 0.0001), age at onset of gavage
      feeds (p < 0.003), oxygenation index (p < 0.007), and gestational age (p < 0.05)
      made a significant contribution to variations in BI (37.16%, 43.71%, 48.99%, and
      53.33%, respectively). CONCLUSION: Hyperbilirubinemia in ventilated preterm
      infants with RDS is most likely multifactorial; entities quite distinct from RDS
      (such as nutrition and IVH) may significantly contribute to its variation.

PMID- 10920785
TI  - Low 1-hour glucose screens and small for gestational age infants.
AB  - OBJECTIVE: To determine whether a 1-hour glucose screen done at 26 to 29 weeks'
      gestation that is below the fifth percentile is predictive of having a small for
      gestational age (SGA) infant. STUDY DESIGN: Pregnancies with 1-hour glucose
      screens were analyzed retrospectively. A total of 600 cases had values below the
      fifth percentile (< 71 mg/dl). A total of 6784 controls had values between the
      25th and 75th percentiles. Infants were classified as being SGA if they had birth
      weights less than the 10th percentile adjusted for gestational age and infant
      gender. The Student's t-test, Fisher's exact test, and logistic regression were
      used for statistical analysis. RESULTS: The incidence of SGA infants differed
      significantly between cases and controls, 16.2% versus 12.0% (p = 0.0043). This
      association remained significant after adjustment for race (p = 0.02).
      CONCLUSION: A 1-hour glucose screen with a result that is less than the fifth
      percentile is an independent risk factor for having an SGA infant.

PMID- 10920786
TI  - Neurodevelopmental and health outcomes in term infants treated with surfactant
      for severe respiratory failure.
AB  - OBJECTIVE: Analysis of health, neurodevelopmental, and school performance
      outcomes in a pilot study of term and near-term infants with respiratory failure
      due to pneumonia or meconium aspiration treated with surfactant. STUDY DESIGN:
      Retrospective review of medical records, neurodevelopmental and psychosocial
      evaluations, and parent and teacher surveys. RESULTS: Of the 14 patients
      enrolled, only one was rehospitalized, for pneumonia. Three were reported to have
      episodes of wheezing, two of whom required bronchodilators. One patient had
      unilateral hearing loss, one had a full-scale intelligence quotient that was
      below normal, and all but one patient for whom complete results were obtained
      were performing at or above grade level. CONCLUSION: Term and near-term newborns
      with moderately severe respiratory failure treated with surfactant can, in
      general, be expected to recover completely and have normal general health,
      neurodevelopmental outcome, and school performance.

PMID- 10920787
TI  - Antecedents of clinically significant pulmonary hemorrhage among newborn infants.
AB  - OBJECTIVE: To evaluate risk factor profiles associated with clinically
      significant pulmonary hemorrhage (PH) in preterm (PT) and term infants. STUDY
      DESIGN: Case-control study of all infants with PH cared for in three Harvard
      affiliated neonatal intensive care units between 1987 and 1994. RESULTS: A total
      of 50 cases of PH occurred in PT infants (gestational age (GA) of < or = 34
      weeks), and 26 cases occurred in near-term/full-term (NT/FT) infants (GA of > 34
      weeks). The median age at the time of PH was 46 hours among PT infants compared
      with 6 hours among NT/FT infants. For PT infants, four factors best predicted PH:
      a GA of between 24 and 26 weeks and antenatal glucocorticoid treatment reduced
      the risk (odds ratios (ORs) of 0.7 and 0.3, respectively), whereas requirement
      for resuscitation with positive pressure ventilation and thrombocytopenia were
      associated with increased risk (ORs of 4.3 and 4.0, respectively). Among the
      NT/FT infants, the model included three variables: meconium aspiration (OR 4.9),
      requirement for resuscitation with positive pressure ventilation (OR 2.9), and
      hypotension (OR 3.5). CONCLUSION: Antecedent factors and timing of PH differ
      between PT and NT/FT infants, suggesting that the mechanisms contributing to PH
      are influenced by developmental maturity as well as perinatal and neonatal
      medical conditions and interventions.

PMID- 10920788
TI  - Perinatal factors influencing hepatic glucose-6-phosphatase enzyme activity.
AB  - BACKGROUND: At discharge from neonatal units, many preterm infants are vulnerable
      to preprandial hypoglycemia due to insufficient liver glucose production. In most
      preterm infants, hepatic glucose-6-phosphatase activity (the terminal step of
      liver glucose production) remains abnormally low postnatally. OBJECTIVE: To
      determine what perinatal factors are associated with changes in hepatic glucose-6
      phosphatase enzyme activity. STUDY DESIGN: The maximum velocity (Vmax) of the
      hepatic microsomal glucose-6-phosphatase enzyme, as the dependent variable, was
      correlated by stepwise multiple regression analysis with clinical data from a
      consecutive series of 45 preterm infants from a level 3 neonatal unit. RESULTS:
      Significant factors (p < or = 0.0005) were the presence of pathogenic bacteria
      isolated from maternal high vaginal swabs (p < or = 0.0000), hyperkalemia
      regimen, duration of prenatal exposure to ritodrine, and delivery mode. Further
      analysis revealed that the highest correlation was with positive early post
      delivery infant bacterial cultures. CONCLUSION: Perinatal events and clinical
      interventions modulate key enzyme systems necessary for human adaptation to
      extrauterine life.

PMID- 10920789
TI  - Mechanical vibration in neonatal transport: a randomized study of different
      mattresses.
AB  - OBJECTIVE: To test the hypothesis that a gel mattress is most effective in
      attenuating mechanical vibration in neonatal transport, we performed a randomized
      block study of four mattress combinations (none, foam, gel, gel on foam) using
      mannequins and an ambulance traveling on fixed routes (city, highway). STUDY
      DESIGN: Mechanical vibration was assessed by measuring vertical accelerations at
      two locations: the forehead of a 2000-gm mannequin and the transport incubator
      base. From time histories of these accelerations, root mean square (RMS) values
      and power spectral density functions were calculated. The effect of the mattress
      on the transmission of vibration was determined from ratios of the RMS values at
      the two locations. An RMS ratio of < 1.0 indicates attenuation, whereas a ratio
      of > 1.0 indicates accentuation of vibration. From the power spectral density
      functions, the natural frequency of the system was determined for each mattress
      combination in relation to the natural frequencies of the ambulance. To determine
      the effect of the weight of the mannequin on vibration, additional measurements
      were performed using a 300-gm mannequin. RESULTS: All the observed RMS ratios
      were > 1. The highest ratios were observed on the city route in the absence of
      the gel mattress. The gel mattress, used alone or with the foam mattress, in
      contrast to foam or no mattress, shifted the natural frequency of the system away
      from the natural frequencies of the ambulance, avoiding a large amplification of
      vibration. A decrease in the weight of the mannequin caused the gel mattress to
      be less effective in attenuating vibration. CONCLUSION: A gel mattress, used
      alone or with a foam mattress, results in the least accentuation of vibration,
      but vibration in ambulance transport is not attenuated by any of the mattress
      combinations. The hazard of vibration may be particularly relevant when
      transporting extremely low birth weight neonates. These findings indicate a need
      for study and design of more effective devices that can reduce the vibratory
      stress.

PMID- 10920790
TI  - Skin-to-skin contact improves gas exchange in premature infants.
AB  - OBJECTIVE: Skin-to-skin contact (kangarooing) is regarded as an important method
      to improve intensive care in premature infants. There is still demand for
      investigations of its impact on physiological parameters. STUDY DESIGN: We
      examined 53 preterm infants of < 1800 gm in a prospective, pretest-test-posttest
      design study during incubator care (60 minutes), skin-to-skin contact (90
      minutes), and incubator care again (90 minutes). Heart rate, respiratory rate,
      oxygen saturation (SaO2), transcutaneous pO2 (tcpO2), transcutaneous pCO2, rectal
      temperature, and fraction of inspired oxygen were measured. RESULTS: The heart
      rate increased during skin-to-skin contact by 5 beats per minute (p < 0.001), the
      respiratory rate dropped by 5/minute (p < 0.01), the SaO2 improved by 0.4% (p <
      0.05) accompanied by an increase of tcpO2 of 4.8 mm Hg (p < 0.001), the tcpCO2
      dropped by 1.2 mm Hg (p < 0.001), and the rectal temperature increased by 0.3
      degree C (p < 0.001). Analyzing three groups separately by postnatal weight, we
      observed the smallest increase in heart rate and the highest decrease in
      respiratory rate in infants of < 1000 gm (p < 0.001). The increase in SaO2 and in
      the tcpO2 doubles in infants of < 1000 gm compared with infants of > 1000 gm (p <
      0.001). All changes were independent of postnatal age. CONCLUSION: During skin-to
      skin contact, preterm infants not only remain clinically stable but also show a
      more efficient gas exchange. Although the patient is removed (transferred) from
      the incubator, there is no risk of hypothermia even in infants of < 1000 gm.

PMID- 10920791
TI  - Indicated preterm birth: a possible contribution to group B streptococcal sepsis
      prophylaxis protocol failures. A case report.
AB  - BACKGROUND: Despite the acceptance of protocols for the prevention of group B
      streptococcal (GBS) sepsis for the newborn, protocol violations, with subsequent
      failure to initiate intrapartum antibiotic therapy, occur at many institutions.
      The causes for GBS prophylaxis protocol violations are not well understood.
      CASES: We report two cases of indicated preterm birth in which appropriate
      antibiotic prophylaxis for GBS sepsis was not initiated. CONCLUSION: In the
      setting of indicated preterm birth, GBS prophylaxis may be overlooked. We suspect
      that the attention given to the medical or fetal complications of indicated
      preterm birth may contribute to the omission of GBS sepsis prophylaxis in these
      situations.

PMID- 10920792
TI  - Continuous skin-to-skin care in the neonatal intensive care unit: kangaroo or
      "'possum" care?

PMID- 10920793
TI  - The incubator and the medical discovery of the premature infant.
AB  - The invention of the incubator in 1880 ignited a dramatic outpouring of popular
      and professional excitement over the prospect of reducing premature infant
      mortality. Yet the technology itself progressed slowly and fitfully over the next
      50 years. The story is worth examining not so much from the standpoint of
      technological progress, but from the perspective of how responsibility for the
      newborn shifted from mothers to obstetricians and eventually pediatricians. It
      also illustrates how the history of technology involves more than invention. The
      invention of the incubator itself was less significant than the development of a
      system to support the device.

PMID- 10920794
TI  - Use of bronchoalveolar lavage to demonstrate squamous epithelial aspiration in
      congenital icthyosis: a case report.

PMID- 10920795
TI  - Placenta accreta and methotrexate therapy: three case reports.
AB  - Placenta accreta is a complication that is rising in incidence. The reported
      experience of methotrexate treatment in the conservative management of placenta
      accreta is scant. Three cases of placenta accreta managed with methotrexate are
      presented. Case 1: A woman had an antenatal diagnosis of placenta percreta. A
      successful manual placental removal occurred on post-cesarean day 16. Case 2: A
      woman had retention of a placenta accreta after a term vaginal delivery.
      Successful dilation and curettage were performed on postpartum day 37. Case 3: A
      woman had an antenatal diagnosis of placenta previa-percreta with bladder
      invasion. A simple hysterectomy was performed on post-cesarean day 46.
      Conservative management and methotrexate treatment resulted in uterine
      preservation in two of our three patients; however, this treatment did not
      prevent significant delayed hemorrhage. In view of the rapid resolution of
      vascular invasion of the bladder, methotrexate may have an important role in the
      management of placenta percreta with bladder invasion. The utility of
      methotrexate treatment with the conservative management of placenta accreta
      requires further evaluation.

PMID- 10920796
TI  - Candida chorioamnionitis after serial therapeutic amniocenteses: a possible
      association.
AB  - BACKGROUND: Reduction amniocentesis is used in cases of severe polyhydramnios to
      decrease maternal discomfort and the risk of preterm labor. In a MEDLINE search
      (1966 to present, English language, keywords: amniocentesis, chorioamnionitis),
      no report of Candida chorioamnionitis after serial reduction amniocentesis
      exists. CASE: A 29-year-old primigravida with a history of four therapeutic
      amniocenteses for idiopathic polyhydramnios developed preterm labor at 30 and 5/7
      weeks' gestation, rupture of membranes, and Candida albicans chorioamnionitis.
      Despite aggressive therapy with amphotericin B, the neonate succumbed to
      overwhelming systemic candidiasis. CONCLUSION: Serial amniocentesis may place
      patients at elevated risk for Candida chorioamnionitis and subsequent preterm
      delivery. Clinicians should consider early diagnostic amniocentesis in patients
      in preterm labor with a history of prior amniocentesis, and the routine Gram
      stain and culture of amniotic fluid.

PMID- 10920797
TI  - Umbilical cord blood gases casebook. Interpreting umbilical cord blood gases,
      VII.

PMID- 10920798
TI  - Special imaging casebook. Retroperitoneal subdiaphragmatic extralobar
      sequestration.

PMID- 10920799
TI  - [Colonial organization and intercellular communication of microorganisms].
AB  - This review covers the modern concepts and recent data demonstrating the
      integrity and coherence of microbial populations (colonies, biofilms, etc.) as
      peculiar "super-organisms." Special attention is given to such relevant phenomena
      as apoptosis, bacterial altruism, quorum effects, collective differentiation of
      microbial cells, and the formation of population-level structures such as an
      extracellular matrix. Emphasis is placed on the channels in colonies and agents
      of intercellular communication in microbial populations. The involvement of a
      large number of evolutionarily conserved communicational facilities and patterns
      of intercellular interactions is underscored. Much attention is also given to the
      role of colonial organization and intercellular communication in
      parasite/commensal/symbiont-multicellular host organism systems.

PMID- 10920800
TI  - [The activity of the carbon metabolism enzymes in Chromatium minutissimum after
      long-term preservation].
AB  - The activity of the enzymes of the tricarboxylic acid cycle and glyoxylate shunt,
      as well as of some enzymes involved in carbohydrate metabolism, were determined
      in the purple sulfur bacterium Chromatium minutissimum, either maintained by
      subculturing in liquid medium or stored in the lyophilized state for 36 years. In
      cultures stored in the lyophilized state, the activities of the key enzymes of
      the tricarboxylic acid cycle, glyoxylate shunt, and Embden-Meyerhof-Parnas
      pathway were higher, whereas the activities of glucose-6-phosphate dehydrogenase,
      pyruvate kinase, and ribulose bisphosphate carboxylase were somewhat lower than
      in cultures maintained by regular transfers.

PMID- 10920801
TI  - [Carbon metabolism in Sulfobacillus thermosulfidooxidans subsp. asporogenes,
      strain 41].
AB  - The activities of carbon metabolism enzymes were determined in cellular extracts
      of the moderately thermophilic, chemolithotrophic, acidophilic bacterium
      Sulfobacillus thermosulfidooxidans subsp. asporogenes, strain 41, grown either at
      an atmospheric content of CO2 in the gas phase (autotrophically,
      heterotrophically, or mixotrophically) or autotrophically at a CO2 content
      increased to 5-10%. Regardless of the growth conditions, all TCA cycle enzymes
      (except for 2-oxoglutarate dehydrogenase), one glyoxylate cycle enzyme (malate
      synthase), and some carboxylases (ribulose bisphosphate carboxylase, pyruvate
      carboxylase, and phosphoenolpyruvate carboxylase) were detected in the cellular
      extracts of strain 41. During autotrophic cultivation of strains 41 and 1269, the
      increase in the CO2 content of the supplied air to 5-10% resulted in the
      activation of growth and iron oxidation, a 20-30% increase in the cellular
      content of protein, enhanced activity of the key TCA enzymes (citrate synthase
      and aconitase), and, in strain 41, a decrease in the activity of carboxylases.

PMID- 10920802
TI  - [Methane production by the sulfate-reducing bacterium Desulfosarcina variabilis].
AB  - The sulfate-reducing bacterium Desulfosarcina variabilis VKM B-1694 was found to
      produce up to 1.62 mumol methane per mg protein when grown on different
      substrates. The role of methanogenesis and the physicochemical factors
      determining this process in sulfate-reducing bacteria are discussed.

PMID- 10920803
TI  - [Alteration of serine/threonine protein kinase activity during growth of the wild
      type Streptomyces avermitilis strain and its chloramphenicol-resistant mutant].
AB  - The dynamics of serine/threonine protein kinase activity during the growth of the
      wild-type Streptomyces avermitilis strain and its chloramphenicol-resistant
      (Cmlr) pleiotropic mutant with an enhanced production of avermectins was studied
      by measuring the transfer of radiolabeled phosphate from [gamma-32P]ATP to the
      serine and threonine residues of proteins in cell-free extracts. In both of the
      strains studied, radiolabeled phosphate was found to incorporate into
      polypeptides with molecular masses of 32, 35, 41, 68, 75, 79, 83, and 137 kDa;
      however, the degree and the dynamics of phosphorylation of particular peptides
      were different in these strains. The differences revealed could not be accounted
      for by the interference of ATPases or phosphoprotein phosphatases. The data
      obtained may be interpreted as evidence that Cmlr mutation activates the protein
      kinase signalling system of S. avermitilis cells in the early stationary growth
      phase and thus enhances the production of avermectins and leads to some other
      physiological changes in the mutant strain.

PMID- 10920804
TI  - [Regulation of the adhesion of Pseudomonas fluorescens cells to glass by culture
      produced volatile compounds].
AB  - The effect of the gaseous metabolites of one Pseudomonas fluorescens culture on
      the attachment of cells of another Pseudomonas fluorescens culture to glass was
      studied. Gaseous metabolites increased the number of unattached cells by 10-30%
      and the mean residence time of cells attached to glass by 100%. These effects
      were presumably due to the yet unidentified compound, which we called volatile
      antiadhesin. This compound could be adsorbed by activated carbon and HAYESEP-Q
      adsorbent.

PMID- 10920805
TI  - [Role of distant cellular communications in regulation of Pseudomonas fluorescens
      adhesion].
AB  - The effects of long-range interactions (LRI) and culture air on the adhesion of
      Pseudomonas fluorescens cells were studied. One P. fluorescens culture was found
      to diminish the adhesion of cells of another, glass-screened, P. fluorescens
      culture by 30%. This effect was interpreted to be due to penetrating LRI. Under
      the combined action of LRI and culture air (the latter alone reduced cell
      adhesion by only several percent), the amount of unattached cells increased 2- to
      30-fold (on the average, by a factor of nine). Such a great reduction of cell
      adhesion indicated the synergistic action of LRI and culture air.

PMID- 10920806
TI  - [The distinctive features of the structure of the Pseudomonas fluorescens IMV 247
      (biovar II) lipopolysaccharide].
AB  - The results of the study of the Pseudomonas fluorescens IMV 247 (biovar II)
      lipopolysaccharide (LPS) isolated from the dry bacterial mass by Westphal's
      method and purified by repeated ultracentrifugation are presented. The
      macromolecular organization of the LPS is characterized by the presence of S and
      R forms of LPS molecules in a 1:1 ratio. The structural components of the LPS
      molecule--lipid A, the core oligosaccharide, and the O-specific polysaccharide-
      were isolated and characterized. 3-Hydroxydecanoic, 2-hydroxydodecanoic, 3
      hydroxydodecanoic, and dodecanoic acids proved to be the main lipid A fatty
      acids. Glucosamine, phosphoethanolamine, and phosphorus were identified as the
      components of the lipid A hydrophilic portion. Glucose, galactose, arabinose,
      rhamnose, glucosamine, alanine, phosphoethanolamine, phosphorus, and 2-keto-3
      deoxyoctulonate (KDO) were revealed in the heterogeneous fraction of the core
      oligosaccharide. The O-specific polysaccharide chain was composed of repeating
      tetrasaccharide units consisting of L-rhamnose (L-Rha), 3,6-dideoxy-3-[(S)-3
      hydroxybutyramido]-D-glucose (D-Qui3NHb), 2-acetamido-2,4,6-trideoxy-4[(S)-3
      hydroxybutyramido-D-glucose (D-QuiNAc4NHb), and 2-acetamido-2-deoxy-D
      galacturonic acid (D-GalNAcA) residues. A peculiarity of the O-specific
      polysaccharide was that it released, upon partial acid hydrolysis, the
      nonreducing disaccharide GalNAcA-->QuiNAc4NHb with a 3-hydroxybutyryl group
      glycosylated intramolecularly with a QuiN4N residue. Double immunodiffusion in
      agar and lipopolysaccharide precipitation reactions revealed no serological
      interrelationship between the strain studied and the P. fluorescens strains
      studied earlier.

PMID- 10920807
TI  - [Screening of marine bacteria for fucoidan hydrolases].
AB  - Twenty-five strains of epiphytic marine bacteria isolated from the brown algae
      Fucus evanescens and Chorda filum and fifty-three bacteria isolated from the sea
      cucumber Apostichopus japonicus were screened for fucoidanases using fucoidans
      prepared from the brown algae F. evanescens, Laminaria cichorioides, and L.
      japonica. Eighteen bacterial epiphytes and thirty-eight bacterial isolates from
      the sea cucumber were found to contain fucoidanases, which were able to hydrolyze
      either all of the fucoidans studied or some of them. Bacteria of the genera
      Cytophaga and Alteromonas/Pseudoalteromonas exhibited the highest fucoidanase
      activities, which, however, did not exceed the activity of fucoidanases from the
      already known sources.

PMID- 10920808
TI  - [Reproductive resting forms of Arthrobacter globiformis].
AB  - Submerged cultures of Arthrobacter globiformis grown in media unbalanced with
      respect to carbon and nitrogen sources were found to contain cells exhibiting
      features typical of resting forms: long-term viability, specific ultrastructure,
      dormant metabolism, and thermoresistance. Such cells were produced not only in
      the collection strain VKM B-1112, but also in the A. globiformis strains isolated
      from 2- to 3-million-year-old permafrost sediments.

PMID- 10920809
TI  - [Formation of resting forms of Arthrobacter globiformis in autolysing cell
      suspensions].
AB  - Under conditions of spontaneous or induced autolysis of thick cell suspensions,
      Arthrobacter globiformis strains produced cells exhibiting features typical of
      resting microbial forms. The number of viable resting cells was greater under
      conditions of induced rather than spontaneous autolysis. The thermoresistance of
      the resting cells of A. globiformis strains isolated from 2- to 3 million-year
      old permafrost was higher than that of the collection A. globiformis strain.

PMID- 10920810
TI  - [Characteristics of morphology and ultrastructure of bacteria of the genus
      Dethiosulfovibrio].
AB  - Cell morphology and fine structure were studied in two strains of rod-shaped,
      strictly anaerobic, gram-negative sulfidogenic bacteria: strain SR12T (DSM 12538)
      and strain WS100 (DSM 12537) belonging to "Dethiosulfovibrio starorussensis."
      Cells of both strains, as well as cells of the type species of the genus
      Dethiosulfovibrio, D. peptidovorans, were found to possess multiple intracellular
      incomplete cross septa in the stationary growth phase.

PMID- 10920811
TI  - [Heliobacterium sulfidophilum sp. Nov. and Heliobacterium undosum sp. Nov.:
      sulfide-oxidizing Heliobacteria from thermal sulfidic springs].
AB  - Two new species of heliobacteria isolated from cyanobacterial mats of two
      alkaline sulfidic hot springs are formally described. Strains BR4 and BG29 are
      assigned to anoxygenic phototrophic bacteria of the family Heliobacteriaceae,
      since they possess the unique properties of this taxon: strict anaerobiosis,
      formation of bacteriochlorophyll g, the lack of extensive intracytoplasmic
      membranes and chlorosomes, an unusual cell wall structure, and phylogenetic
      relatedness to the low G + C gram-positive eubacteria. Based on the 16S rDNA
      sequence similarity, strains BR4 and BG29 are assigned to the genus
      Heliobacterium and described as two new species of this genus: Heliobacterium
      sulfidophilum sp. nov. and Heliobacterium undosum sp. nov. The G + C content of
      the DNA is 51.3 mol % in Hbt. sulfidophilum and 57.2-57.7 mol % in Hbt. undosum.
      The cells of Hbt. sulfidophilum are rods, and the cells of Hbt. undosum are
      slightly twisted spirilla or short rods. Both new bacteria are motile by
      peritrichous flagella. Hbt. sulfidophilum produces endospores. The new bacteria
      are strict anaerobes growing photoheterotrophically on a limited range of organic
      compounds. In the dark, they can switch from photosynthesis to the slow
      fermentation of pyruvate. Biotin is required as a growth factor. Both species are
      highly tolerant to sulfide (up to 2 mM at pH 7.5) and oxidize it
      photoheterotrophically to elemental sulfur; photoautotrophic growth was not
      observed. The temperature optimal for growth of Hbt. sulfidophilum and Hbt.
      undosum is 30-35 degrees C, and the optimal pH is 7-8.

PMID- 10920812
TI  - [Characteristics of hemagglutination reaction in methanotrophic bacteria].
AB  - The reaction of hemagglutination with trypsin-treated rabbit erythrocytes was
      used to reveal lectins on the cell surface of methanotrophic bacteria and in
      their culture liquids. By this method, no lectins were detected on the cell
      surface of Methylococcus capsulatus IMV B-3001 and Methylomonas rubra IMV B-3075
      or in the culture liquid of any of the species studied. With intact cells of
      Methylocystis parvus IMV B-3491, the positive hemagglutination reaction observed
      was nonspecific and most probably occurred due to the high cell surface
      hydrophobicity characteristic of this species.

PMID- 10920813
TI  - [Saccharomyces bayanus var. Uvarum comb.nov., a new variety established by
      genetic analysis].
AB  - Partial genetic isolation of two Saccharomyces bayanus varieties, S. bayanus var.
      bayanus and S. bayanus var. uvarum comb. nov., was established by hybridological
      analysis. The hybrids of these two varieties were semisterile: their ascospores
      were characterized by low survival. Earlier, the new variety was described as a
      group of cryophilic wine yeast cultivars capable of fermenting melibiose.

PMID- 10920814
TI  - [Taxonomic position and nitrogen-containing secondary metabolites of the fungus
      Penicillium vitale Pidoplichko Et Bilai Apud Bilai].
AB  - The type strain Penicillium vitale Pidoplichko et Bilai apud Bilai 1961 VKM F
      3624 was found to considerably differ from a sibling species P. janthinellium
      (syn. P. simplicissimum) in some physiological and morphological features (growth
      rates at different temperatures, the size of philiades, and the shape of
      conidia), as well as in the pattern of the nitrogen-containing secondary
      metabolites produced (roquefortine, 3,12-dihydroroquefortine, meleagrin,
      aurantioclavine, indole-3-acetic acid, and N-acetyltryptamine). The data obtained
      suggest that P. vitale represent an independent species.

PMID- 10920815
TI  - [Effect of phosphorus on the colonization of barley rhizosphere by
      microorganisms].
AB  - The mineral phosphorus supply produced two outbreaks in the bacterial population
      of the barley rhizosphere and rhizoplane but inhibited the growth of fungal
      mycelium. The inhibition of mycelial growth might be due to the exudation of
      specific inhibitors by barley roots, since the most pronounced inhibition was
      observed at high doses of supplementary phosphorus.

PMID- 10920816
TI  - [Effect of temperature and soil moisture content on the colonization of the wheat
      rhizosphere by antipytopathogenic Bacillus Cohn].
AB  - Vegetative experiments showed that the population density of antiphytopathogenic
      bacillar species introduced into the rhizosphere of spring wheat seedlings
      essentially depended on soil temperature and not on the soil moisture content. As
      a rule, the population of introduced bacilli increased with temperature. Under
      both low and optimal soil moisture contents, introduced bacilli were efficiently
      acclimated in the wheat rhizosphere.

PMID- 10920817
TI  - [On the vertical distribution of microorganisms in lake Baikal during spring deep
      water renewal].
AB  - The vertical distribution of microorganisms during spring deep-water renewal in
      Lake Baikal was studied. The downward advection of trophogenic waters was found
      to create conditions for the extensive growth of microorganisms capable of
      decomposing and mineralizing organic carbon, nitrogen, and phosphorus in deep
      water layers. These processes occur annually at spring thermal bars near the
      underwater slope of Lake Baikal, whereas in its pelagic zone, the deep intrusions
      of waters rich in organic material are observed only in the years when enhanced
      deep-water renewal is accompanied by a high spring yield of phytoplankton.

PMID- 10920818
TI  - [Biological activity of ancient cultivated soil with buried horizons (the
      Iverskii monastery, XVII century)].
AB  - The biological activity of an ancient cultivated soil that has been in intense
      agricultural use since approximately the first half of the XVII century was
      studied. The potential biological activity of the buried horizon of the antient
      cultivated soil was higher than that of its modern horizon or that of the
      noncultivated soil of an adjacent territory occurring under similar lithological
      and geomorphological conditions. A decrease rate of oxidative processes
      (decreased rates of CO2 production and CH4 oxidation) and an increased rate of
      reductive processes (denitrification and nitrogen fixation) were found in the
      buried horizon. A high potential denitrification activity (with predominant
      formation of nitrous oxide) was found in the buried horizon; in the upper
      horizon, the end product was molecular nitrogen.

PMID- 10920819
TI  - [Phylogenetic position of Desulfurococcus amylolyticus].

PMID- 10920820
TI  - [Central neurocytoma].

PMID- 10920821
TI  - [Endoscopic evacuation of intraventricular hematoma and third ventriculostomy].
AB  - We described our experience of three cases treated with endoscopic evacuation of
      intraventricular hematoma and third ventriculostomy for a tight intraventricular
      hematoma associated with intracerebral hemorrhage. A steerable endoscope was
      introduced into the anterior horn of the lateral ventricle contralaterally to the
      intracerebral hemorrhage, through a 14 Fr. peel-away sheath. First, the hematoma
      in the lateral ventricle contralateral to the hemorrhage was evacuated by direct
      aspiration using a syringe connected to the operative channel of the endoscope,
      and evacuation of the hematoma was subsequently carried on the third ventricle,
      aqueduct and the fourth ventricle. After the evacuation of the intraventricular
      hematoma, third ventriculostomy was performed for acute obstructive
      hydrocephalus. Finally, the procedure was completed with septostomy and
      evacuation of the hematoma in the lateral ventricle ipsilateral to the
      hemorrhage. Sufficient evacuation of the hematoma was obtained in all cases and
      no major complications were encountered. We conclude that for patients with
      intraventricular hematoma associated with intracerebral hemorrhage endoscopic
      evacuation of intraventricular hematoma brings about sufficient removal of
      hematoma, reduction of hospitalization time and prevention of subsequent
      hydrocephalus.

PMID- 10920822
TI  - [Clinical application of portable near infrared oximetry (HEO-200) to
      neurosurgical monitoring].
AB  - Near infrared spectroscopy (NIRS) have been accepted as a useful modality for non
      invasive monitoring of brain oxygenation state. Using a newly developed NIRS
      apparatus, HEO-200, the authors continuously monitored the changes in the
      oxygenation state of brain hemoglobin during carotid endarterectomy (CEA) or
      carotid balloon occlusion tests (BOT) in 21 patients. Somatosensory evoked
      potentials (SEP), regional cerebral blood flow (rCBF) or transcranial Doppler
      sonography (TCD) were also employed to compare with the NIRS-responses. In 7 of
      21 patients, the carotid artery occlusion caused a continuous deoxygenation of
      brain hemoglobin as well as a decrease in total hemoglobin. These findings
      correlated well with temporary neurological deficits and a marked reduction of
      rCBF in the ipsilateral hemisphere in patients who underwent carotid BOT under
      local anesthesia. The patients also showed a marked decrease in the N20 amplitude
      of SEP during CEA under general anesthesia. Restoration of blood flow immediately
      resolved these findings. The other 14 patients demonstrated no or only transient
      changes on NIRS as well as on SEP and rCBF study. HEO-200 could non-invasively
      monitor the relative changes of cerebral oxygenation state with good time
      resolution, and detect critical ischemia during CEA and carotid BOT.

PMID- 10920823
TI  - [Benefits of 0.5T MR diffusion-weighted images for super-acute-phase cerebral
      infarction].
AB  - Though diffusion-weighted images (DWI) have been increasingly used to detect
      super-acute-phase cerebral infarction in recent years, they have primarily been
      obtained through the use of high magnetic machines of more than 1.5T. In this
      study, we discussed the usefulness of DWI obtained using 0.5T MRI in comparison
      with CT, MRI (FLAIR and T2 weighted image) and SPECT (99mTc-HMPAO). DWI were able
      to detect ischemic lesions earlier than FLAIR or T2-weighted images. Scanning
      time was short at four seconds for eight slices, and the quality of image was
      sufficient for clinical usage. The most available b-value seems to be 800. There
      were less susceptibility artifacts in the 0.5T DWI than in the 1.5T DWI. From
      these data, we presume that it is possible to detect super-acute-phase cerebral
      ischemia on the 0.5T DWI, proving the clinical usefulness of DWI. Furthermore,
      DWI is considered useful in observing chronological changes in cerebral
      infarction, differentiation of abscess or brain tumor, diagnosis of moyamoya
      disease, degenerative disease and so on.

PMID- 10920824
TI  - [Metabolic acidosis and ketone body in severely head-injured patients].
AB  - Increase of ketone body concentration in plasma is induced by various factors
      such as onset of diabetes. Secretion of excessive stress hormone including
      catecholamine is responsible for stimulation of lipolysis which increases plasma
      ketone body concentration. Catecholamine levels reflect the severity of the
      neurologic insult, so this is a basis for the use of catecholamine measurements
      as a physiological marker of patient outcome. Twenty-seven patients with severe
      head injury and twenty-five healthy volunteers were enrolled in this study, but
      patients with diabetes or liver dysfunction were excluded. The patients with
      severe head injury consisted of 19 with focal injury and 8 with diffuse injury.
      The outcome was as follows; 14 patients died and 13 patients survived. We
      collected arterial blood samples as promptly as possible after onset of severe
      head injury and measured the following: 1, base excess; 2, beta-hydroxybutyrate;
      3, acetoacetate; 4, lactate; 5, epinephrine; 6, norepinephrine. The ketone body
      (beta-hydroxybutyrate + acetoacetate) concentration in plasma was significantly
      elevated in patients with severe head injury. The increment of beta
      hydroxybutyrate levels was greater than that of acetoacetate levels, resulting
      decreased arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutyrate).
      We demonstrated that plasma ketone body concentrations were elevated and the AKBR
      decreased in severe head-injured patients. Elevation of catecholamine has been
      reported as a stress reaction in severe head injury. Catecholamine is most potent
      in stimulating lipolysis, and ketogenesis. Therefore, the ketonemia observed in
      severe head injury is most likely to be induced by elevation of catecholamine
      levels. The degree of ketonemia may be an index of the severity of severe head
      injury.

PMID- 10920825
TI  - [Two cases of pyogenic cervical discitis presenting tetraparesis].
AB  - The authors reported two cases of pyogenic cervical discitis presenting
      tetraparesis. Case 1: A 66-year-old male patient entered the hospital because of
      tetraparesis. Two weeks before the hospitalization, he had become feverish and
      awakened with motor weakness in all extremities. Magnetic Resonance Imaging (MRI)
      study revealed a lesion filling the anterior epidural space from C4 to C6 levels
      and posterior displacement of the spinal cord. Findings suggesting discitis of
      C5/6 and osteomyelitis of C5 and C6 were also obtained on MRI. These findings
      suggested that the tetraparesis was caused by cord compression by the epidural
      abscess as the acute stage of pyogenic spinal infection. On the day following
      admission, surgical removal of the epidural abscess and of the infected bodies
      was performed. Spinal fusion through C4 to C7 was also carried out with iliac
      bone graft. Antibiotic administration and Halo-vest application were performed
      after the operation. The postoperative course was good and the tetraparesis had
      completely disappeared within 12 months after the operation. Case 2: A 60-year
      old male patient entered the hospital because of tetraparesis. Since 6 weeks
      before the hospitalization, he had become feverish and suffered from pain in the
      neck. He had also awakened with motor weakness of all extremities. The
      tetraparesis was progressive. Plain X-ray films of the cervical spine showed
      destructive change of C5 and C6 and kyphotic displacement. An epidural abscess of
      the cervical spine at the level of C4 to C6, discitis of C5/6 and osteomyelitis
      of C5 and C6 were diagnosed on MRI findings. The disarranged kyphotic vertebral
      bodies and the epidural abscess caused posterior displacement of the spinal cord.
      Based on these findings, it was concluded that the abscess and the kyphotic
      change of the bodies had been induced by spinal infection in the subacute stage.
      On the 8th hospital day, surgical removal of the anterior portion of the infected
      bodies as well as fusion of the vertebral column from C4 to C7 was performed.
      Iliac bone was used for the fusion graft. Postoperative administration of
      antibiotics and Halo-vest application for external fixation were carried out. On
      the 7th postoperative day, symptoms caused by radiculopathy of the left C5
      appeared, but gradually ameliorated. The patient was free from motor weakness in
      the 8th month after the surgical treatment. Surgical intervention is a useful
      treatment for pyogenic cervical discitis with symptoms due to compression of the
      spinal cord both in the acute and subacute stages.

PMID- 10920827
TI  - [A case of high flow CCF with congestive hemorrhage].
AB  - The authors report a case of high flow CCF with intracerebral hemorrhage during
      treatment with endovascular coil embolization. A 52-year-old woman had been in
      good health until a sudden onset of orbital bruit and left orbital tinnitus
      occurred. Conjunctival chemosis and diplopia caused by left abducens palsy
      gradually progressed. Left internal carotid arteriography revealed a carotid
      cavernous sinus fistula with direct high-flow shunt. The fistula drained into the
      superior orbital vein, inferior petrosal sinus, intercavernous sinus and
      sphenoparietal sinus with significant cortical reflux. The attempt at
      transarterial balloon occlusion failed. Then transvenous coil embolization was
      performed. During the course of endovascular treatment, follow up CT depicted
      intracerebral hemorrhage. Intracerebral hemorrhage was asymptomatic and thought
      to be caused by venous hypertension from cortical reflux. The patient underwent
      direct occlusion of the left sphenoparietal sinus for prevention of further
      hemorrhage via craniotomy. Lastly, the cavernous sinus was completely occluded by
      transvenous coil embolization. The signs and symptoms resolved 3 months after the
      procedures.

PMID- 10920826
TI  - [Transvenous embolization for cavernous dural arteriovenous shunts: about the
      intracranial venous approach to the cavernous sinus].
AB  - Recently, the first choice of therapy for cavernous dural arteriovenous shunts
      (CdAVS) is transvenous embolization. Usually the approach routes for cavernous
      sinus are the inferior petrosal sinus (IPS), the superior ophthalmic vein (SOV)
      in most cases and the superior petrosal sinus (SPS) in rare case. But, it is
      difficult for us to treat patients in whom there are no extracranial veins
      through which to approach the cavernous sinus, with transvenous embolization. We
      presented the case in which intracranial transvenous approach to the cavernous
      sinus and transvenous embolization were performed and in which we achieve good
      results. In this article, we presented a case with Barrow's type D CdAVS and
      cortical venous drainage. At first, transarterial embolization was performed to
      decrease the amount of venous drainage for the purpose of eliminate convulsions
      and consciousness disturbance. However, cortical venous drainage continued.
      Moreover bilateral dilated SOVs normalized and bilateral IPSs were not visible,
      so we decided that it was impossible to carry out the transvenous embolization
      via extracranial veins. Transvenous embolization to the left cavernous sinus via
      the intracranial ophthalmic vein between the superior ophthalmic fissure and the
      inferior ophthalmic fissure after craniotomy was performed. Then, the transvenous
      embolization to the right cavernous sinus was carried out through the right
      superficial middle cerebral vein after craniotomy. The results were good and
      chemosis and bilateral abducens palsy diminished immediately. Trans-intracranial
      venous embolization for CdVAS is a very useful therapy when no extracranial veins
      exist for transvenous embolization.

PMID- 10920828
TI  - [Superselective fibrinolysis for a middle cerebral artery embolism caused by a
      left atrial myxoma: case report].
AB  - A case of successful treatment by local fibrinolysis of a middle cerebral artery
      embolism caused by a thrombus from a left atrial myxoma is reported. A 62-year
      old woman using a pacemaker and suffering from sick sinus syndrome was admitted
      on December 29th 1996, complaining of transient restlessness. CT and cerebral
      angiography revealed no abnormal vascular lesions. Eighteen months after the
      initial episode, she suffered a sudden onset of left hemiparesis and loss of
      consciousness. CT scan performed during the second episode revealed no lesions
      and, in particular, no early CT infarction sign, but emergent cerebral
      angiography revealed a right middle cerebral artery embolic occlusion. Local
      fibrinolysis using a tissue plasminogen activator was performed within 3 hours
      after the beginning of the episode, and partial recanalization was obtained
      within one hour after initiation of the fibrinolytic therapy. On the first
      hospital day, though CT revealed a small low-density area in the right basal
      ganglia, motor deficits gradually improved. Considering the possibility of a
      cardiac source of the embolism, trans-esophageal echocardiography was performed
      and revealed a left atrial tumor suspected to be a myxoma. It was removed by
      surgery on the 34th hospital day. Histological examination proved it to be a
      myxoma. Nine months after local fibrinolytic therapy, the patient returned to
      work. The diagnosis of cerebral embolism caused by cardiac myxoma is difficult to
      make at the time when the patient is first examined after admission. It is also
      hard to discover during emergent cerebral angiography with fibrinolytic therapy.
      Therefore, in the case of patients with cerebral embolism for which local
      fibrinolysis is ineffective, it should be presumed that cardiac myxoma is the
      source of the embolus. Direct PTA alone may be effective for such tumoral
      embolism.

PMID- 10920829
TI  - Article's definition of complementary and alternative medicine too narrow.

PMID- 10920830
TI  - Preventing crises in the patient with cancer.
AB  - Despite what the title of this presentation implied, no magic pills are available
      that can be given to prevent patients from getting very sick or falling off that
      thin line between physical compensation and critical illness. A large part of the
      prevention of crises comes from redefining the nature of what you view as a
      crisis and being prepared for the worst possible scenario. The reality is that
      some patients will develop complications, most of which will be reversible with
      early interventions. No matter what we do, some patients cannot and will not
      survive a complication. Your role is pivotal in recognizing high-risk patients,
      guiding discussions regarding treatment preferences, assisting in defining the
      treatability of specific complications, and providing care directed at the
      appropriate therapeutic goals.

PMID- 10920831
TI  - Pathos in practice: exploring the affective domain of oncology nursing.

PMID- 10920832
TI  - Effects of advanced nursing care on quality of life and cost outcomes of women
      diagnosed with breast cancer.
AB  - PURPOSE/OBJECTIVES: To evaluate quality of life (QOL) and cost outcomes of
      advanced practice nurses' (APNs') interventions with women diagnosed with breast
      cancer. DESIGN: Randomized clinical trial. SETTING: Integrated healthcare system
      in a midwestern suburban community. SAMPLE: 210 women with newly diagnosed breast
      cancer with an age range of 30-85 years. METHODS: The control group (n = 104)
      received standard medical care. The intervention group (n = 106) received
      standard care plus APN interventions based on Brooten's cost-quality model and
      the Oncology Nursing Society's standards of advanced practice in oncology nursing
      QOL was measured using the Functional Assessment of Cancer Therapy, Mishel
      Uncertainty in Illness Scale and Profile of Mood States at seven intervals over
      two years. Information about costs (charges and reimbursement) was collected
      through billing systems. MAIN RESEARCH VARIABLES: Uncertainty, mood states, well
      being, charges, and reimbursement. FINDINGS: Uncertainty decreased significantly
      more from baseline in the intervention versus control group at one, three, and
      six months after diagnosis (p = 0.001, 0.026, and 0.011, respectively), with the
      strongest effect on subscales of complexity, inconsistency, and unpredictability.
      Unmarried women and women with no family history of breast cancer benefited from
      nurse interventions in mood states and well-being. No significant cost
      differences were found. CONCLUSIONS: APN interventions improved some QOL
      indicators but did not raise or lower costs. IMPLICATIONS FOR NURSING PRACTICE:
      The first six months after breast cancer diagnosis is a critical time during
      which APN interventions can improve QOL outcomes. More research is necessary to
      define cost-effective interventions.

PMID- 10920833
TI  - Improving pain management: an ongoing journey.

PMID- 10920834
TI  - Anemia.
AB  - PURPOSE/OBJECTIVES: To review the current knowledge of anemia associated with
      cancer management and nursing interventions. DATA SOURCES: Published theory,
      research, and clinical practice sources. DATA SYNTHESIS: Anemia often is
      overlooked as a priority associated with quality patient care. The diagnosis of
      cancer and associated treatments magnify the incidence of anemia among the cancer
      population. Untreated anemia negatively affects the success of radiation therapy,
      activities of daily living, quality of life, and morbidity and mortality.
      CONCLUSIONS: Identifying the underlying cause(s) of anemia in patients with
      cancer is critical to positive care outcomes and requires early nursing
      assessment and interventions. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a
      critical role in maintaining and improving well-being and quality of life of
      patients at risk for anemia by understanding erythropoiesis, pathophysiology,
      nursing assessment (including laboratory data assessment), and nursing
      interventions related to anemia.

PMID- 10920835
TI  - Development of an opioid-taper algorithm for hematopoietic cell transplant
      recipients.
AB  - PURPOSE/OBJECTIVES: To describe an opioid taper algorithm for hematopoietic cell
      transplant (HCT) recipients and its development. DATA SOURCES: Nonresearch-based
      published guidelines, published research on opioid withdrawal symptoms, clinical
      experience, and multidisciplinary consultant recommendations. DATA SYNTHESIS:
      Many HCT recipients receive opioid therapy for several weeks and thus become
      physically dependent on opioids. If opioids are discontinued abruptly or tapered
      too rapidly, patients may experience discomfort from withdrawal symptoms. An
      algorithm can guide clinicians in providing patient care. CONCLUSIONS: No
      research-based opioid-taper guidelines exist in the literature; existing
      guidelines vary widely and are not specific to HCT recipients. Thus, the
      algorithm addresses a gap in the literature and also provides flexibility when
      dealing with patient discomfort. IMPLICATIONS FOR NURSING PRACTICE: Use of an
      algorithm may promote consistency of opioid tapering and patient comfort.

PMID- 10920837
TI  - Pain intensity and pain interference in hospitalized patients with cancer.
AB  - PURPOSE/OBJECTIVES: To examine relationships among pain intensity, interference
      in daily life because of pain, reported pain relief, and analgesics prescribed in
      hospitalized patients with cancer. DESIGN: Cross-sectional, descriptive. SETTING:
      The internal medicine services of two acute-care facilities, an academic medical
      center, and a community hospital in the northeastern United States. SAMPLE: 176
      patients with cancer, 139 of whom reported pain during hospitalization. Mean age
      of the sample was 59 years, 50% were women, and 79% were Caucasian. METHODS:
      Patients were interviewed in their hospital rooms to obtain information about the
      major variables using the Brief Pain Inventory-Short Form and the Pain Management
      Index. Demographic, clinical, and analgesic prescription data were obtained from
      patients' medical records. MAIN RESEARCH VARIABLES: Pain intensity, pain-related
      interference, and pain relief analgesic adequacy. FINDINGS: The prevalence of
      pain in the sample of 176 patients was 79%. Of the 139 patients who experienced
      pain during hospitalization, a strong positive correlation was found between
      worst pain intensity and interference, which was not appreciably altered by
      surgery or procedures conducted during hospitalization. Although patients with
      metastatic disease reported greater pain intensity and interference than patients
      without metastases, they were more likely to have adequate analgesics prescribed.
      CONCLUSION: Findings suggest that pain interferes with daily life and that higher
      levels of pain produce greater interference. Adequate analgesics were prescribed
      for a majority of the patients, yet levels of worst pain remained severe for 46%
      of the sample. IMPLICATIONS FOR NURSING PRACTICE: These findings reinforce the
      need to assess and treat pain in hospitalized patients with cancer. Nurses need
      to be aware of the prescribed dose of analgesics and administer a dose that
      provides adequate pain relief.

PMID- 10920836
TI  - Comparison of Florida Hispanic and non-Hispanic Caucasian women in their health
      beliefs related to breast cancer and health locus of control.
AB  - PURPOSE/OBJECTIVES: To compare Florida Hispanic and non-Hispanic Caucasian women
      in their health beliefs about breast cancer and health locus of control (LOC).
      DESIGN: Exploratory, comparative. SETTING: A variety of healthcare settings in an
      urban area in Florida. SAMPLE: Hispanic (n = 113) and non-Hispanic (n = 197)
      Caucasian women who could read and understand either English or Spanish. METHODS:
      The Health Screening Questionnaire, which assesses health beliefs and health LOC,
      was administered in either Spanish or English, and the results were analyzed.
      MAIN RESEARCH VARIABLES: Attitudes about health in general, perceptions about
      susceptibility to cancer, beliefs about benefits of early diagnosis, and
      perceptions about the seriousness of cancer; LOC. FINDINGS: Florida Hispanic
      women are better educated than the Mexican American Hispanic women described in
      the literature. Hispanic and non-Hispanic women were significantly different in
      their health beliefs and LOC. With age and education controlled statistically,
      these differences remained. Hispanic women who preferred to speak/read English
      were more like the non-Hispanic women in their responses than were the women who
      preferred Spanish. CONCLUSIONS: Cultural differences exist between Hispanic and
      non-Hispanic women; however, differences also exist between groups of Hispanic
      women in Florida versus Hispanics in the southwestern United States. IMPLICATIONS
      FOR NURSING PRACTICE: Outreach programs for cancer screening should be culturally
      relevant and may need to be different for subgroups of Hispanics in the United
      States.

PMID- 10920838
TI  - [The phylogeny of the Trypanosomatidae: the molecular and morphological
      approaches].
AB  - The results of comparative analysis of two phylogenetic trees of the
      trypanosomatids based on morphological and molecular characters are discussed.
      The morphological dendrogram was based on 33 ultrastructural characters, 6 light
      microscope characteristics and 8 biological characters. Molecular UPGMA
      dendrogram depicting differences (Dice distance) between examined trypanosomatids
      is based on the universally primed PCR polymorphisms. The general topology of
      both dendrograms are similar, with the Trypanosoma at the base. The genus
      Wallaceina appears to be monophyletic. In a contrary, the genera Leptomonas,
      Crithidia and Herpetomonas look like artificial groups according to both methods
      used. The cyst-forming homoxenous trypanosomatids from insects represent a
      monophyletic clade, which seems to be a separate genus. Two species of within
      genus Wallaceina are arranged as a separate subgenus.

PMID- 10920839
TI  - [Further comment on the coccidian nature of cryptosporidia (Sporozoa:
      Apicomplexa)].
AB  - The coccidian nature of the genus Cryptosporidium was undoubtedly accepted by
      Tyzzer who was the first to describe this sporozoan parasite in 1907. Electron
      microscopic studies made in 70-90s demonstrated the intracellular, although
      extracytoplasmic localization of Cryptosporidium spp. The pattern of
      Cryptosporidium life cycle fits well that of other intestinal homogeneous
      coccidian genera of the suborder Eimeriina: macro- and microgamonts develop
      independently, a microgamont gives rise to numerous male gametes, oocysts serving
      for parasite's spreading in the environment. Along with these characters,
      Cryptosporidium spp. demonstrate some secondary peculiarities (an endogenous
      phase of development in microvilli of epithelial surfaces, two morphofunctional
      types of oocysts, the smallest number of sporozoites per oocyst, a multi
      membraneous "feeder" organelle etc.), which may be due presumably to their early
      acquisition of specialization in the course of evolution. The recent studies
      based on molecular sequence data (18S rRNA) applied to 8 eimeriid and isosporid
      coccidian genera (Morrison, Ellis, 1997), suggested that the subclass Coccidia
      (class, according to Morrison and Ellis) be considered monophylic if
      Cryptosporidium were excluded, and this genus was regarded as the sister group to
      the rest of the Apicomplexa, or as the sister to the suborder (class) Hematozoa
      within the Apicomplexa. Either of these placements of Cryptosporidium definitely
      conflicts with both the generally accepted taxonomic scheme by Levine (1982) and
      the phenotypically based phylogeny of the phylum Apicomplexa (Barta e. a., 1990).
      The author's opinion is that the differences between the examined eimeriid and
      isosporid coccidia, on the one hand, and Cryptosporidium, on the other hand,
      provided by molecular sequence data, may testify primarily to the well known
      morphofunctional dissimilarities between the compared organisms, rather than cast
      doubt on the coccidian nature of Cryptosporidium. Again, these data can hardly
      prove that Cryptosporidium does not belong to the coccidia. Thus, the modern
      molecular sequence data, despite their obvious scientific value, would make sense
      for phylogeny estimation only, if they are critically analysed and considered in
      combination with results of the relevant basic research.

PMID- 10920840
TI  - [The parasitic communities of the minnow (Phoxinus phoxinus L>)].
AB  - Phoxinus phoxinus being a widely distributed through Palaearctic and ecologically
      specialised species is a good model to study parasite communities. 72 specimens
      of P. phoxinus from 5 localities of the Siberia and Mongolia has been studied by
      the author and 651 specimens--from 5 localities in Kola Peninsula by the other
      researches. 595 specimens were studied by B. S. Shulman (1983) year around. To
      describe infra- and component parasite communities the Brillouin, Shannon, Berger
      Parker indexes were used. Communities within individual fish were compared
      within, and between localities with quantitative percentage similarity index
      (Esch e. a., 1988). The Brillouin, Shannon and Berger-Parker indexes can be
      calculated based on abundance or total number of parasites of each species for
      component or compound communities. Intensity cannot be used. Significant negative
      correlation was observed between the Brillouin and Berger-Parker dominance
      indexes (r = -0.984, p < 0.01, n = 66) in infracommunities. The Brillouin index
      was significant positive correlated with the number of parasites in
      infracommunity (r = 0.407, p < 0.01, n = 66) and with the number of species in
      infracommunity (r = 0.92, p < 0.01, n = 66). Berger-Parker dominance index was
      significant negative correlated with the number of parasite in infacommunity (r =
      -0.815, p < 0.01, n = 66) and with the number of species in infracommunity (r = 
      0.268, p < 0.05). Total number of parasites and the number of species in
      infracommunity was positive correlated significantly (r = 0.565, p < 0.01, n =
      66). These correlations remain the same at the component community level for the
      Shannon/Berger-Parker indexes (r = -0.965, p < 0.01, n = 10) and total number of
      parasites/number of species (r = 0.789, p < 0.01, n = 10) only. Similarity index
      was not correlate with any other indexes and parameters. No significant
      correlation was found between the Brillouin, Berger-Parker indexes and
      geographical characters of localities (longitude, latitude, altitude above sea
      level). Weak correlation (r = 0.551, p < 0.098, n = 10) was observed only between
      the Berger-Parker dominance index and the latitude. 37 metazoan parasites have
      been found in all localities (specialists--40%, allogenic species--22%, rare
      species--40%). Allogenic generalist species of the genus Diplostomum (D. phoxini
      in most cases) were dominant in 60% of the component communities and 36% of
      infracommunities on average. 20% of the component communities were dominant by
      autogenic specialists Gyrodactylus magnificus and only 12% of the
      infracommunities were dominated by this species. Trematode and nematode larvae
      were core species in most localities. Frequency distribution of infracommunity
      richness varied from locality to locality being overdispersed in combine sample.
      Parasite communities at least on the infracommunity level demonstrate high
      variability of all parameters. Some tendency to decrease the diversity seems to
      be present depending on remoteness from prospective centre of origin of the genus
      Phoxinus.

PMID- 10920841
TI  - [The miracidium microanatomy of Philophthalmus rhionica (Trematoda:
      Philophthalmidae)].
AB  - The study of ultrastructure of Philophthalmus rhionica miracidium was carried
      out. Update the ultrastructures of miracidium were studied in a restricted number
      of species belonging to the families Notocotylidae, Paramphistomatidae,
      Sanguinicolidae, Fasciolidae, Schistosomatidae (Galaktionov, Dobrovolsky, 1998).
      The ultrastructure of representatives of two latter families, Fasciola hepatica
      and Schistosoma mansoni respectively, have been examined most carefully. The
      family Philophthalmidae differs from the families Fasciolidae and
      Schistosomatidae by the aberrant pedogenetic miracidium.

PMID- 10920842
TI  - [The species composition and seasonal dynamics of infusorian species from fishes
      in the bodies of water in the Minusinsk depression].
AB  - The infusoria fauna was examined in 495 specimens of 9 fish species living in
      different water basins of the Minusinsk depression. Data on host associations and
      location of all found infusoria species are given.

PMID- 10920843
TI  - [The species composition and ecological characteristics of trematodes from
      reptiles in the Volga delta].
AB  - In the result of parasitological researches of reptiles of the Volga delta, 17
      species of trematodes belonging to 10 families and 5 orders have been recovered.
      The dynamics of trematodes in reptiles is regulated by transformations of
      biocenoses of the delta depending on fluctuations of the Caspian sea level.

PMID- 10920844
TI  - [An electron microscopic study of Borrelia in the body of the female ixodid tick
      Ixodes persulcatus].
AB  - Borrelia burgdorferi s. lato in naturally infected females of tick Ixodes
      persulcatus were examined by transmission electron microscopy. The Borreliae were
      found in midgut and ovary. Location and ultrastructure of bacteria indicate
      extracellular migration through the midgut epithelium as a preferential way. In
      gonad, the borreliae intracellular situate in ovarian epithelium and oocytes
      before and at the beginning of vitellogenesis. The demonstration of numerous
      spirochetes in the oocytes provides the support for transovarial transmission of
      the agent. Two morphological types of borreliae were observed.

PMID- 10920845
TI  - [4 new species of blackflies (Diptera: Simuliidae) from Central Asia, Siberia and
      the Far East].
AB  - Four new species of blackflies (Diptera: Simuliidae) are described. Helodon
      rezidentsii Yankovsky, sp. n., Khabarovsk Territory, differs from all known
      species of the genus with morphology of eyes consisting only of microommatidii in
      male; from related species H. kamtshaticus (Rubzov, 1940) with large triangular
      posteromedial lobes of branches of genital fork in female; with number of rays of
      primary fan of premandibles (20-22, when in H. kamtshaticus 30-32) in larva.
      Helodon submulticaulis Yankovsky, sp. n., Transbaikalia, differs from related
      species H. multicaulis (Popov, 1968) with number of rays of primary fan of
      mandibles (36-40, when in H. multicaulis 26-28), narrow anterior branches of anal
      sclerite, number of rows of hooks in posterior attachment organ (88-92, when in
      H. multicaulis 78-80) in larva; with morphology of respiratory organ, consisting
      of 5-8 lobes bearing 40-60 tune filaments (in H. multicaulis 3-4 lobes bearing
      more than 150 filaments) in pupa. Sch. samarkandica Yankovsky, sp. n.,
      Uzbekistan, differs from related species Sch. pseudopusilla Rubzov, 1956 with 3
      (not 2 as in Sch. pseudopusilla) hooks in parameres, bifurcated lateral branches
      of X sternite, long projection of gonostyles in male. Schoenbaueria ivdelensis
      Yankovsky, sp. n., Middle Ural, differs from related species Sch. rangiferina
      (Rubzov, 1956) with prolonged gonostyles bearing narrow projection in male; with
      number of rays of secondary fan of premandibles (20-28, when in Sch. rangiferina
      44-48), deep ventral groove of cephalic capsule, number of rows of hooks in
      posterior attachment organ (80-82, when in Sch. rangiferina 70-72) in larva; with
      morphology of respiratory organ (very long stems of 2 and 3 pairs of filaments)
      in pupa.

PMID- 10920846
TI  - [Freshwater bryozoans (Bryozoa: Phylactolaemata) as vectors of salmonid disease].
AB  - Relations of PKX [vector of proliferative kidney disease (PKD)] of reared and
      wild Salmonoidea and Tetraspora bryozoides, the only genus and species of Myxozoa
      found in fresh water Bryozoa, is discussed using recent publications. Both
      organisms were found in several European countries as well as in North America.
      It seems that PKX is a Bryozoa parasite which do not undergo full cycle of
      sporulation in fish.

PMID- 10920847
TI  - [The finding of a cestode in the little auk Alle alle on Franz Josef Land].
AB  - One of 14 dovekeys (Alle alle) investigated in August 1993 on Hooker Island
      (Franz Joseph Land) was found to harbour a single specimen of an early immature
      dilepidid cestode attributed as Alcataenia sp. The rostellum bears a double crown
      of 22 hooks, 0.025-0.027 mm in length. Except Threlfall (1971) there was no
      information concerning dovekey's parasites.

PMID- 10920848
TI  - [New monogeneans from the genus Dionchus (Capsalidae: Dionchinae)].
AB  - Three new species of the monogeneans of the genus Dionchus are described:
      Dionchus paruchini sp. n. from Rachicentron canadus and D. trachuri sp. n. from
      Trachurus trachurus from Indian Ocean, D. major sp. n. from R. canadus from the
      North Vietnamese Gulf. All species are located on gills.

PMID- 10920849
TI  - [Clinical pharmacology: proteins for the transport of drugs].
AB  - Most drugs have to pass cellular barriers in order to reach their site of action.
      This can be accomplished passively by diffusion, but more often it is an energy
      consuming process using specific carrier proteins. Two groups of such proteins
      which are well characterised, the organic cation transporters and the multidrug
      resistance proteins, are discussed in detail in the present review. The clinical
      significance of these proteins is due not only to their role in drug distribution
      and elimination, but also to possible drug interactions when different drugs
      and/or endogenous substrates compete with the same carrier protein. Inhibition of
      multidrug resistance proteins could be of therapeutic value in impairing
      transport of drugs from their site of action and this could be particularly
      beneficial in the treatment of malignant diseases.

PMID- 10920850
TI  - [Experiences with the Port-A-Cath system in children].
AB  - In a retrospective study (1987-1997) the complications of a totally implantable
      venous access device (Port-A-Cath, Fa. Pharmacia, Germany) were analysed in 91
      children with 99 implants. All but 2 of these children had malignant diseases.
      Their age ranged from 0.1 to 18.1 (median 6) years. Overall implant time was
      171.2 years (62,488 days), averaging 1.63 years (595 days) per device. 11
      complications were registered, i.e. infections (6), occlusions (4) and
      disconnection (1), resulting in an overall infection rate of 0.06 and a total
      occlusion rate of 0.04. The overall complication rate was thus 0.11, which
      compares favourably with other studies. With careful handling, the Port-a-Cath
      device is very reliable and involves few complications.

PMID- 10920852
TI  - [New knowledge on the pathogenesis of chronic inflammatory bowel diseases: what
      have we learned from colitis animal models?].
AB  - In recent years it has been possible to establish animal models with colitis by
      immunological and genetic manipulation. Such animal models share characteristic
      features with human inflammatory bowel disease. The fact that different immune
      defects induce inflammation in the intestines supports the theory of
      heterogeneity in the pathogenesis of human inflammatory bowel disease. Discrepant
      results concerning the disease association with genetic markers have been
      obtained in different populations, which may confirm the concept of
      heterogeneity. So far it has not been possible to identify one single factor
      which is aetiologically responsible for the development of inflammatory bowel
      disease. The intestinal inflammation is normally T cell-dependent and caused by a
      dysbalance of pro- and anti-inflammatory immune responses. Interestingly, animals
      kept under germfree conditions do not develop disease. Thus, the intestinal
      bacterial flora plays a crucial role. The loss of immune tolerance towards these
      bacterial antigens is an important current concept in the pathogenesis of
      inflammatory bowel disease.

PMID- 10920851
TI  - [Psychological comorbidity and quality of life of patients with morbid obesity
      and requesting gastric banding].
AB  - Bariatric surgical operations are well established in the treatment of morbid
      obesity. In this study, 79 consecutive applicants for laparoscopic gastric
      banding (60 females with a mean BMI of 47.4 kg/m2 and 19 males with a mean BMI of
      48.9 kg/m2, mean age 39.6 years) were examined preoperatively by structured
      psychiatric interview and questionnaire. GOAL AND QUESTIONS: The aim of the study
      was to determine physical and psychological symptoms, specific eating problems,
      life satisfaction and incidence of psychiatric comorbidity, as well as the
      relations between psychological and psychosocial markers on the one hand, and
      demographic and somatic parameters on the other. RESULTS: Most patients displayed
      multiple somatic symptoms and diseases, in particular orthopaedic problems,
      exertion dyspnoea, hyperlipidaemia, hypertension, diabetes mellitus or sleep
      apnoea. The averages of all psychometric scales (General Symptomatic Index of
      Symptom Checklist [SCL-90-R], anxiety and depression states of the Hospital
      Anxiety and Depression Scale [HADS]) were higher than normal. General life
      satisfaction and satisfaction with health (FLZM) were low. Eating behaviour in
      both sexes was characterised by marked irritability, disinhibition and
      ravenousness. Binge eating was common, 27% reporting binges at least weekly and
      only 37% no binges at all. 46% were found to suffer from at least one psychiatric
      disorder, while half had an eating disorder with frequent bingeing and loss of
      control. 6.3% were diagnosed with atypical bulimia, 15.2% had an adaptational
      disorder and 10% a personality disorder. The HADS scales did not correlate with
      BMI or other somatic factors and the correlation between the SCL-90-R and BMI was
      low (r = 0.36, p = 0.01). However, patients with psychiatric disorders had
      significantly higher BMIs and higher averages on all scales except overall life
      satisfaction. There was no direct relation between psychosocial and
      sociodemographic variables (educational level, living alone). CONCLUSION:
      Morbidly obese patients desiring laparoscopic gastric banding display many
      physical and psychological symptoms with a higher preference for psychiatric
      (especially eating) disorders. Since there is no close relationship between
      psychosocial and somatic aspects in this group of patients, routine psychiatric
      evaluation appears to be of importance.

PMID- 10920853
TI  - [Horseshoe kidney and aneurysm of the abdominal aorta].

PMID- 10920854
TI  - [A morphological and karyometric study of the secretory cells in mint].
AB  - Morphological and karyometric peculiarities of oil-synthesizing secretory
      structures in mint forms differing by rate of oil biosynthesis were investigated.
      Significant similarity in morphology of secretory structures in investigated
      forms during differentiation and functioning was shown. Character of changes in
      karyometric properties of oil-synthesizing cells also was similar: nuclear and
      nucleolar volumes increased and then decreased during differentiation of
      secretory structures. A functional increase of nuclear and nucleolar volumes was
      found at the stage before essential oil secretion. Higher parameters at all
      stages of differentiation and before secretion were revealed in highly oil
      production mint. This fact may serve as indirect indicator of increased
      functional activity of oil-synthesizing cells and intensity of oil-producing
      process. The obtained results are discussing with well-known data.

PMID- 10920855
TI  - [The actin cytoskeletal characteristics of the root meristem cells in Beta
      vulgaris L. at different mitotic stages].
AB  - For the first time the actin cytoskeleton in meristem cells of B. vulgaris root
      has been studied. It was established that all discovered earlier patterns of
      microfilament arrangement were also specific for meristem of present species.
      Specific rearrangements of actin in the sites of spindle (prophase) and
      phragmoplast formation (telophase) were revealed. It is supposed, that actin
      cytoskeleton determines certain position of spindle in cells and takes part in
      the cell plate formation.

PMID- 10920856
TI  - [The effect of the plasmon on the inheritance of resistance to Septoria nodorum
      Berk. in soft wheat].
AB  - The genetic control of resistance to Septoria nodorum in common wheat line
      Transec have been investigated. There have been concluded that high level of
      resistance of this line is connected with the presence in its genome of partially
      recessive gene which is located on wheat-rye translocation T4BS.4BL-2RL or
      closely linked with it. Plant plasmon can have an influence on inheritance of
      resistance to Septoria blotch in hybrid progeny.

PMID- 10920858
TI  - [The effect of alien genomes on the diploidization system in wheat].
AB  - Comparative investigation of Elymus sibiricus and other cereal genomes influence
      on wheat diploidization system was carried out. Elymus sibiricus genome was
      revealed to have a promoting effect on nonhomologous pairing, however, it is not
      sufficient for successful introgression of alien genes into wheat. Strain
      specific influence of rye genome on nonhomologous chromosome pairing is noted
      under interaction with ph1b mutation.

PMID- 10920857
TI  - [The effect of the genome of the variety on the adaptive characteristics of
      alloplasmic strains of winter wheat].
AB  - The analysis of adaptability and genetical distances between 12 cytoplasms of
      Aegilops, Triticum and Haynaldia villosa for three winter wheat genomes showed an
      existence of genome-plasmon interactions. The plasmons of Ae. variabilis, Ae.
      cylindrica, Ae. squarrosa var. strangulata, T. dicoccoides appeared to be
      perspective in practical breeding for adaptability. Interactions are revealed as
      alteration of productivity and adaptability, and as genetic divergence.

PMID- 10920860
TI  - [The heat-shock reaction is disturbed in a Drosophila virilis strain incapable of
      a neurohormonal stress reaction].
AB  - Cellular stress response was investigated in two lines of D. virilis: wild type
      and line with disturbed neurohormonal stress-reaction. Analysis of proteins,
      synthesized in salivary glands of larvae of both lines under heat stress,
      revealed malfunction in heat shock reaction of mutant specimen. This malfunction
      expresses in decreased level of heat shock protein synthesis. Analysis of
      electrophoretic spectra of proteins from homogenates of imagoes of both lines
      maintained under normal conditions and those exposed to heat (38 degrees C, 60
      min.) revealed correlation between protein spectrum and physiological state of
      the organism. Interlinear differences by proteins spectra in normal condition,
      controlled by a single gene (or by block of closely linked genes), were found.
      The question if there is a common genetic control for the neurohormonal stress
      reaction and cellular stress response is discussed.

PMID- 10920859
TI  - [A genetic analysis of endocrine diseases of the thyroid and pancreas].
AB  - The genetic determination of insulin-dependent (IDDM) and non-insulin-dependent
      (NIDDM) diabetes mellitus and thyroid gland diseases (TGD) was carried out using
      clinical-genealogical data on 229 patients with IDDM, 275 patient with NIDDM, 247
      patients with TGD and their relatives. Results of component decomposition showed
      the role of genetic factors in the determination of these diseases and the
      existence of interloci interaction in genetic control of IDDM and NIDDM. The
      genetic independence of these diseases and genetic homogeneity of NIDDM were
      revealed using models of Ch. Smith and T. Reich.

PMID- 10920861
TI  - [The prevalence of cytogenetic anomalies in children with congenital
      developmental defects (CDD)].
AB  - The analysis of the cytogenetic anomalies frequencies in children with inborn
      defects of development was carried out, and the comparative evaluation of
      involving in cytogenetic anomalies of the individual chromosomes was determined.
      Chromosomes 9, 13 and 18 were most frequently involved in chromosomal anomalies.
      There no direct relations were revealed between peculiarities of inborn defects
      of development and definite cytogenetic anomalies.

PMID- 10920862
TI  - [The cytotoxic effect of heavy metals on an L-cell culture].
AB  - The dependence of some parameters of L-cells culture viability on different
      concentrations of heavy metals was studied. Considerable cytotoxic effect of low
      concentrations of nickel (0.025 mcg/ml) and lead (0.05 mcg/ml) was shown. Copper
      and chrome at concentrations of 0.25-0.5 mcg/ml promote cells proliferation
      between third and fifth days of cultivation. Nickel at concentration 0.025 mcg/ml
      and lead at all investigated concentrations synchronize cells division in
      culture. Increasing of giant polynucleas cells level in culture was
      characteristic for investigated metals. The maximum levels of this type cells
      were caused by the action of nickel, chrome and copper.

PMID- 10920863
TI  - [Apoptosis in the cells of parenchymatous organs in subacute sodium nitrate
      poisoning].
AB  - Subacute intoxication was induced by the oral administration of sodium nitrate
      200 mg/kg during 150 days to Wistar rats. After the time had been up severe
      damaging were found in liver, kidney, heart and thymic tissues. In the liver
      cells the DNA fragmentation in "scale" manner was found, but not in kidney and
      heart cells. Simultaneously, the Ca2+, Mg(2+)-depended endonucleases activity
      were increased in the liver nuclei extracts under intoxication. It was suggested
      that increasing of apoptosis in liver is the universal reaction to toxins.

PMID- 10920864
TI  - [The modern concepts on the primary cell walls of angiosperm plants].
AB  - The modern view on polysaccharide composition of the primary cell wall of
      angiosperm plants was considered, and five classes of structural proteins were
      characterized. The model which shows location of enzyme complex synthesizing
      cellulose, as well as structural model of primary cell walls of the most
      flowering plants were presented. Besides, there were shown cell wall reactions to
      environmental factors which have contradictory character and have to be deeply
      and thoroughly analyzed.

PMID- 10920865
TI  - [V. N. Lebedev--100 years (1899-1957)].

PMID- 10920866
TI  - [Loss of heterozygosity on chromosome 17p13.3 in ovarian cancer and cervical
      cancer].
AB  - OBJECTIVE: To identify the loss of heterozygosity (LOH) on chromosome 17p13.3 in
      ovarian cancer and cervical cancer. METHODS: The frequency of LOH on chromosome
      17p13.3 in DNA samples from 24 ovarian cancers, 9 cervical cancers, and 13 non
      malignant gynecological diseases were determined respectively, using Southern
      blot method with probe PYNZ. 22. RESULTS: LOH on 17p13.3 was found in 12 of 24
      (50.0%) ovarian cancers (including a borderline mucinous cystadenoma), 4 of 9
      (44.4%) cervical carcinomas, and 1 of 13 (7.7%) non-malignant gynecological
      diseases, which was cervical intraepithelial neoplasm III (CIN III) (P < 0.01).
      CONCLUSION: These results show that LOH on 17p13.3 is associated with ovarian
      cancer and cervical cancer, suggesting that detection of LOH on 17p13.3 may be
      helpful to understand the molecular pathogenesis of ovarian cancer and cervical
      cancer.

PMID- 10920867
TI  - [Deletion of MTS1/p16 gene in endometrial carcinoma].
AB  - OBJECTIVE: To investigate the possible relationship between deletion of MTS1/p16
      gene and progression of endometrial carcinoma. METHODS: Thirty two primary
      endometrial carcinoma, 7 tumor-adjacent endometrial tissue and 10 normal
      endometrial tissue specimens were examined for homozygous deletion of MTS1/p16
      gene by polymerase chain reaction-based analysis. RESULTS: Of 32 endometrial
      cancer specimens, 6(18.8%) showed homozygous deletion of MTS1/p16 gene. No
      deletion was detected in the tumor-adjacent and normal endometrial tussues. Nor
      was it detected in well differentiated endometrial carcinoma. CONCLUSIONS:
      Deletion of MTS1/p16 gene might contribute to the progression of endometrial
      carcinoma and could be served as indicator for predicting prognosis.

PMID- 10920868
TI  - [The effect of antibody against vascular endothelial growth factor (VEGF) on
      tumor metastasis].
AB  - OBJECTIVE: To study whether manipulation of angiogenesis with antibody against
      vascular endothelial growth factor (VEGF) may interrupt the tumor growth and
      metastasis. METHODS: IV TA2MA 891 is a murine spontaneous breast cancer with high
      rate of metastasis in lung in (TA2x615) F1 mice, and it was chosen as an animal
      model in this study because of the high expression of VEGF in primary tumor as
      well as in lung metastatic tumor. The mice were injected with anti-VEGF
      polyclonal antibody at a dose of 200 micrograms/mouse/day from day 9 to 23
      following s.c. tumor inoculation and sacrificed on day 26. RESULTS: The growth of
      primary tumor was inhibited by 44.0% and the number and size of metastatic foci
      in the lungs were inhibited by 73.0% and 83.7% respectively. CONCLUSION: The
      antibody against human VEGF may be a potentially effective antimetastasis agent
      for the treatment of patients with lung metastasis.

PMID- 10920870
TI  - [Study on rearrangements of immunoglobulin genes in acute nonlymphocytic
      leukemia].
AB  - OBJECTIVE: To explore the mechanism of infidelity of immunoglobulin gene
      rearrangements in acute nonlymphocytic leukemia and its significance in
      genotyping of acute leukemia. METHODS: Immunoglobulin gene rearrangement was
      studied in 25 patients with acute nonlymphocytic leukemia in various stages by
      polymerase chain reaction. RESULTS: Immunoglobulin heavy chain gene
      rearrangements were detected in three of 25 patients, one of whom in complete
      remission was found to have tendency of relapse one month later. CONCLUSION:
      Lineage infidelity of immunoglobulin gene rearrangements does exist in acute
      nonlymphocytic leukemia, therefore, immunoglobulin rearrangements probably can
      not be regarded as an absolutely reliable marker for acute lymphocytic leukemia.
      Immunoglobulin rearrangements may have some significance in the detection of
      minimal residual disease of acute leukemia.

PMID- 10920869
TI  - [Exogenous mtsl/p16 gene suppresses tumorigenicity of human gastric cancer cell
      line].
AB  - OBJECTIVE: To determine the effect on cell growth and tumorigenicity of mstl/p16
      gene in human gastric cancer cell line. METHODS: mtsl/p16 gene vector was
      constructed and transfected into PAMC82 cells which retains down-regulated
      mtsl/p16 gene expression. Integration and expression of exogenous mtsl/p16 gene
      were confirmed by PCR, Northern blot, mRNA in situ hybridization and Western blot
      techniques. Cell morphology was observed in regular culture medium and
      tumorigenicity in nude mice. RESULTS: The growth of the cells transferred with
      mtsl/p16 gene (named as PAMCp16) was dramatically inhibited in nude mice as
      compared to that of the parental PAMC82 cells. Histologically, the tumor grown
      from PAMCp16 cells was much better differentiated than that from the parental
      ones. CONCLUSION: Tumorigenicity of a human gastric cancer cell line in nude mice
      can be inhibited by transduced exogenous mtsl/p16 gene. mtsl/p16 gene may have
      potential value in gene diagnosis and gene therapy.

PMID- 10920871
TI  - [Identification of a novel gene overexpressed in hepatocellular carcinoma by
      differential hybridization].
AB  - OBJECTIVE: Searching for novel gene related to human hepatoma. METHODS: Twelve
      EST (expressed sequence tag) clones were examined with Northern blot analysis,
      looking for the gene(s) differentially expressed in hepatoma versus surrounding
      noncancerous hepatic tissue, and then compared with Gene Databases. RESULTS:
      Northern blot analysis showed that EST clone F9391 expressed at high level in all
      of the 6 hepatocellular carcinoma samples, but at low level in the surrounding
      noncancerous hepatic tissues and in 2 cases of normal liver tissues. Nucleotide
      sequencing indicated that this clone belonged to a novel gene that had not
      included in the Gene Databases (EMBL 96.6). CONCLUSION: F9391 gene is a novel
      gene overexpressed in hepatocellular carcinoma. Being related to cell
      proliferation, it might play an important role in liver oncogenesis. Forthermore,
      it may be used as a new marker for diagnosis and new target for treatment of
      hepatocellular carcinoma.

PMID- 10920872
TI  - [Inherent mdr-1 gene expression in fresh tumor tissue specimens from several high
      incidence malignancies].
AB  - OBJECTIVE: To ascertain frequency of inherent mdr-1 gene expression in several
      common neoplasms. METHODS: One hundred fifty one surgically resected tumor
      specimens confirmed pathologically to be malignant from preoperatively untreated
      cancer patients were studied. Expression of mdr-1 gene was examined by RT-PCR.
      RESULTS: The frequency of primary mdr-1 gene expression was 33.3% for cancer of
      the stomach and gastric cardia (17/51), 37% for cancer of the esophagus (17/46),
      31.3% for cancer of the colon and rectum (5/16), 13.2% for cancer of the breast
      (2/15), 40.0% for cancer of the thyroid (4/10), 55.0% for cancer of the lung
      (5/9) and 0% for cancer of the uterine cervix (0/4). CONCLUSION: Primary mdr-1
      gene expression is relatively of frequent occurrence as detected by RT-PCR
      technique.

PMID- 10920873
TI  - [Inhibitory effect of samarium-153-labeled ethylenediaminetetramethylene
      phosphonate (EDTMP) on bone invasion and osteolysis in Walker 256 carcinoma
      bearing rats].
AB  - OBJECTIVE: To investigate the inhibitory effect of samarium-153 EDTMP on bone
      invasion and osteolysis in Walker 256 carcinoma bearing rats. METHODS: Invasion
      and resorption of tibia by Walker 256 carcinoma in rats were evaluated by X-ray
      and histological examination. RESULTS: Intravenous administration of 153Sm-EDTMP
      at a dose of 74 or 148 MBq/kg, the rat numbers with tibia invasion and bone
      resorption were reduced by fifty percent. 153Sm-EDTMP at a dose of 37 MBq/kg
      still exhibited inhibitory effect on bone invasion and osteolysis as compared
      with the control group. However, there was no indication of change in the weight
      of primary tumor even at the highest dose utilized. CONCLUSION: Samarium-153
      EDTMP can inhibit bone invasion and osteolysis by Walker 256 carcinoma in rats,
      but it has no effect on the growth of the transplanted tumor. Therefore, that the
      effect of 153Sm-EDTMP is due to a reduction in tumor growth leading to decreased
      bone invasion and osteolysis can be reasonably ruled out.

PMID- 10920874
TI  - [Correlation analysis of radiation effects on potential doubling time (Tpot) for
      human nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To understand radiation-induced cell kinetic changes of human
      nasopharyngeal carcinoma CNE cells and clarify cell biology basis of
      repopulation. METHODS: Either exponential growing stage or plateau stage human
      nasopharyngeal carcinoma CNE cells were measured by BrdUrd/DNA bivariate flow
      cytometry for phase fraction, BrdUrd labeling index, S phase duration, potential
      doubling time (Tpot), etc. Correlation analysis of Tpot with other kinetic
      parameters was made. RESULTS: (1) For exponentially growing CNE cells, shortening
      of Tpot after irradiation was closely correlated with increased BrdUrd labeled S
      phase fraction (P < 0.05), whereas no correlation was found between Tpot and
      other kinetic parameters measured; (2) for plateau stage CNE cells, shortening of
      Tpot with various radiation doses was closely correlated with decreased G0/G1
      phase fraction (P < 0.05) and increased G2M phase fraction (P = 0.002), whereas
      no correlation was found between Tpot and other parameters measured. CONCLUSION:
      In a range of 0-8 Gy of irradiation, an increased accelerated repopulation rate
      was resulted from increasing radiation dose. Recruitment of G0 cells into cell
      cycle might play a major role in radiation-induced accelerated repopulation for
      plateau stage CNE cells, while it was contributed by an increased DNA synthesis
      manifested by an increased BrdUrd labeled S phase fraction for exponential
      growing CNE cells.

PMID- 10920875
TI  - [Photodynamic effect of 49 single laser photosensitizers on two human tumor cell
      lines in vitro].
AB  - OBJECTIVE: For comparing the photodynamic effect of 49 single laser
      photosensitizers on two human cancer cell lines. METHODS: After irradiation with
      a pulsed copper vapour laser, the SW1116 cell line of human colorectal cancer and
      K562 cell line of erythroleukemia were measured with MTT assay. IC50 and the cell
      survival rate were observed to evaluate the photodynamic effect of various 49
      single photosensitizers. RESULTS: In 49 photosentizers, the structure formula of
      the leading 9 single photosensitizers belonged to homatoporphyrin group, the
      average IC50 of which was < or = 1.0 microgram/ml on both cell lines of. The
      photosensitizers currently used in the clinic, hematoporphyrin-3 (PSD-007),
      ranked 17th, with IC50 on both cell lines of 1.25 micrograms/ml and 3.75
      micrograms/ml, respecively. CONCLUSION: The leading 16 single photosensitizer in
      ths series studied are better purified and more effective in photodynamic killing
      of human cancer cell lines in vitro. They can be used in lieu of PSD-007 for
      cancer treatment.

PMID- 10920876
TI  - [Adenosquamous carcinoma of the lung. A radiologic and pathologic study].
AB  - OBJECTIVE: To study if there are characteristic radiologic features of
      adenosquamous carcinoma (ASC) of the lung and correlations of histo-pathologic
      components with radiologic findings and prognosis. METHODS: Fifty one
      pathologicall confirmed ASC cases (52 foci) were reviewed. All had chest
      radiographs, CT scans were available in 23 cases and MRI in 6 cases. These cases
      were subdivided into three groups according to the amount of adenocarcinoma
      component on microscopic manifestations: less than 40%, 40%-60%, and more than
      60%. RESULTS: (1) Radiologic findings: In three cases, the tumor was of central
      type and in 48 cases (94.1%) of peripheral type. The size of tumor varied from 2
      to 15 cm in diameter (mean, 5.7 cm). All the peripheral tumors were lobulated. In
      19 cases (39.6%) the tumors were well demarcated, but poorly defined in 18 cases
      (19 foci) (37.5%) and spiculated in 14 cases (29.2%). Eccentric cavities with
      thickened wall were seen in 8 cases (15.7%) and pleural tag in 12 cases (25%).
      (2) Correlations between the amount of adenocarcinoma component and radiologic
      features: There were no statistically significant differences among the three
      groups with regard to tumor location, margin, and pleural tag. CONCLUSION: The
      radiologic findings of ASC are not specific; the most common finding is a
      peripheral mass. The amount of adenocarcinoma component is not significantly
      related with the radiologic features and prognosis.

PMID- 10920877
TI  - [Development of quality of life questionnaire for Chinese cancer patients
      receiving chemobiotherapy].
AB  - OBJECTIVE: To develop the quality of life questionnaire for Chinese cancer
      patients receiving chemobiotherapy (QLQ-CCC), and to study the methodology
      involved in the construction of scales measuring quality of life of cancer
      patients. METHODS: From April, 1993 to April, 1995, QLQ-CCC had been developed
      mainly according to the Rolls-Royce model: 30 items were iuitially identified and
      tested in advance, from which the "best" items were selected to from the final
      format of QLQ-CCC (the fourth-generation questionnaire) including 35 questions.
      RESULTS: QLQ-CCC had 35 items mainly concerning the five different aspects of
      cancer patients. Physical aspect included 16 items, of which 9 were
      disease/treatment-related (specific items), and 7 non-specific items.
      Psychological/spiritual, social and general health aspects had 5, 5 and 9 items,
      respectively. CONCLUSION: Quality of life (QOL) research in cancer patients is
      conducted primarily through the development, implementation and assessment of QOL
      scales. QOL scales adopted in the developed countries, owing to difference in
      sociocultural background, have to be modified according to China's concrete
      condition. This study is an attempt to set up our own QOL scales for cancer
      patients.

PMID- 10920878
TI  - [Debulking operation for non-small cell lung cancer].
AB  - OBJECTIVE: To assess effectiveness and influencing factors of debulking operation
      for non-small cell lung cancer. METHODS: The cumulative survival and its
      influencing factors were analyzed and compared by the Kaplan-Meier and Cox model
      of SPSS for Windows in 244 patients received debulking operation and 364 received
      thoracotomy. RESULTS: The 1, 3, 5-year cumulative survival of patients treated
      with debulking operation was 56.9%, 20.6%, 17.5% respectively while that received
      thoracotomy was 41.1%, 7.8%, 5.3%, respectively (debulking vs thoracotomy,
      Breslow = 27.55, P < 0.0001). Multivariate analysis showed that the debulking
      operation or thoracotomy (B = -0.4600, P < 0.0001) and postoperative adjuvant
      therapies (B = -0.1059, P = 0.0216) were the most important influencing factors
      on the cumulative survival. CONCLUSION: Tumor debulking operation is an important
      treatment for stage III, IV non-small cell lung cancer. With postoperative
      adjuvant chemoradiotherapy better survival can be achieved.

PMID- 10920879
TI  - [Paclitaxel (Tesu) as a single agent in the treatment of breast cancer].
AB  - OBJECTIVE: To evaluate the efficacy and the side effects of paclitaxel (Tesu) in
      breast cancer patients. METHODS: Tesu was administered at 175 mg/m2(170.9-210.8
      mg/m2) to 22 patients with advanced breast cancer from March to July 1995. Tesu
      was given once in 21 days as one cycle, and the patients recieved 1-4 cycles
      (median: 3 cycles) of treatment. RESULTS: Tesu induced 3 complete responses and
      11 partial responses. The duration of remission was 2-7 months (median 3.5
      months). The most frequent toxicities associated with Tesu administration were
      leukopenia, alopecia and myalgias. CONCLUSION: Tesu as a single agent is
      effective in the treatment of breast cancer and the side effects are tolerable.

PMID- 10920880
TI  - [Clinical application of ultrasound(US)-guided percutaneous microwave coagulation
      therapy for liver cancer].
AB  - OBJECTIVE: To evaluate clinical application of US-guided percutaneous microwave
      coagulation therapy for liver cancer. METHODS: 32 patients with 57 nodules of
      liver cancer were treated, 57 nodules were coagulated by 92 times at 182
      different points. Output of one coagulation was 60 W last mg 240-300 sec.
      RESULTS: The follow-up period was 5-18 months, averaging 10.4 months. 29 patients
      remained alive, 3 patients died. After treatment, 85.9%(49/57) of the nodules
      decreased in size; color blood flow signal disappeared in 78.2(36/46) nodules on
      color and energy Doppler scans; and there was no enhancement in 76.4%(25/34)
      tumors on enhanced CT scans. In 13 patients with increased AFP level before
      therapy, it dropped to normal after treatment in 11 patients. Of 27 patients
      whoes a good general condition was good, 19 patients gained bodies weight.
      Repeated biopsy in 14 cases showed complete tumor necrosis with fibrosis in 12.
      CONCLUSION: US-guided percutaneous microwave coagulation therapy is able to
      induce total tumor necrosis of liver cancer in most cases. It can be expected as
      an important non-operative therapy of liver cancer.

PMID- 10920881
TI  - [Study of estrogen receptors in hepatocellular carcinoma and its response to anti
      estrogen therapy].
AB  - OBJECTIVE: To study the usefulness of anti-estrogen therapy for moderately and
      advanced hepatocellular carcinoma (HCC). METHODS: Estrogen receptors (ER) were
      examined in 51 cases of HCC by immunohistochemical staining of needle aspiration
      biopsy HCC specimens. The cases studied were randomly divided into two groups:
      the control group (N = 25) and the anti-estrogen treated group (N = 26). Patients
      in the control group were given matelin and immune RNA while those in the anti
      estrogen treated group were given Tamoxifen in addition. A 50% reduction of serum
      AFP level and a 50% decrease in tumor size were considered therapeutically
      effective. RESULTS: In the control group, the response rate as judged by AFP
      level (RR-AFP) and by tumor size (RR-TS) in the ER+ patients was 42.9% (3 of 7
      cases) and 14.3% (1 of 7 cases), respectively, while the 2 RRs in the ER-
      patients were lower but the difference was statistically insignificant. In
      contrast, in the Tamoxifen-treated group, RR-AFP was 83.3% (5 of 6 cases) and RR
      TS was 50.0% (3 of 6 cases). The difference in RRs of ER+ patients in the 2
      groups was statistically significant. No complete remission was observed.
      CONCLUSION: Endocrinotherapy may be of value in the treatment of ER+ HCC.

PMID- 10920882
TI  - [The observation on treatment effects of local adoptive immunotherapy in 33 cases
      with head and neck cancer].
AB  - OBJECTIVE: To evaluate treatment effects of local adoptive immunotherapy in 33
      cases with head and neck cancer. METHODS: IL-2 1 x 10(5)-2 x 10(5) U per day was
      injected into tumor for 10 days; during the 4th-8th day LAK cells 1.0 x 10(8)-5.0
      x 10(8) per day were combined with IL-2 injection. Then we analysized clinical
      effect, immunopathology, side effects, etc. RESULTS: CR was seen in 1 case; PR in
      6, MR in 20 cases, and SD in 6 cases. The one-, two- and three-year survival rate
      was 96.3%, 83.3% or 75.0% respectively. The results of histopathology showed that
      there were large amount of T lymphocytes (CD3+/4+) infiltrating in the tumor area
      after immunotherapy. No serious side effects were found during the course of the
      treatment. CONCLUSION: Local injection of IL-2/LAK can be used as immunotherapy
      for head and neck cancer.

PMID- 10920883
TI  - [Supra-aortic arch esophageal mucosa-gastric wall anastomosis with oblique
      stomach invagination through esophageal bed for patients with esophageal
      carcinoma undergone esophagectomy].
AB  - OBJECTIVE: To reduce impairement of pulmonary function by thoracic stomach and
      other postoperative complications. METHODS: One hundred eighteen patients with
      esophageal carcinoma were treated with supra-aortic arch esophageal mucosa
      gastric wall anastomosis with oblique stomach invagination through esophageal
      bed. RESULTS: No anastomotic leakage or gastroesophageal reflux occurred. The
      incidence of anastomotic stricture was 2.5%, that of operative mortality was
      0.9%. Cardiopulmonary complications occurred in 11.0%. CONCLUSION: The procedure
      may keep the normal anatomical and physiological functions of the thoracic organs
      and help prevent other complications.

PMID- 10920884
TI  - [Phase III clinical studies with ondansetron (Qilu) in the prophylaxis of nausea
      and vomiting induced by non-cisplatin chemotherapy].
AB  - OBJECTIVE: This study was undertaken to further determine the clinical value of
      ondansetron (OND, supplied by Qilu Pharmaceutical Company) in the prophylaxis of
      nausea and vomiting induced by non-cisplatin chemotherapy. METHODS: A total of
      193 patients were enrolled in the multicenter prospective study and were given
      treatment of non-cisplatin based chemotherapy. All patients were treated with OND
      8 mg i.v. once a day during chemotherapy, followed by OND 4 mg orally twice a day
      for one day after chemotherapy. RESULTS: The effective control rate (0-2 emetic
      episodes) on the first day was 93.3%. Total control of delayed vomiting (day 2-5)
      was as high as 94.8 to 99.5%. The mean frequency of vomiting was 0.4, 0.4, 0.2,
      0.1 and 0.1, respectively from day 1 to day 5. Adverse effects were minor and
      tolerable. CONCLUSION: This modified regimen of treatment with OND is effective
      in the control of vomiting induced by non-DDP chemotherapy.

PMID- 10920885
TI  - [Whole bladder wall laser irradiation to prevent bladder cancer recurrence with
      intravesical HpD and ascorbic acid].
AB  - OBJECTIVE: To evaluate the effect of whole bladder wall laser irradiation with
      intravesical HpD and ascorbic acid on bladder cancer recurrence. METHODS:
      Photodynamic therapy(PDT) was performed by intravesical instillation of
      hematoporphyrin derivative (HpD) PsD-007 containing ascorbic acid followed by
      whole bladder wall laser irradiation in 30 post-operative cases of bladder
      cancer. RESULTS: The tumour recurrence rate was 23.3% (7/30) on follow-up for 30
      months after PDT. No photo-sensitizing effects was found on the skin of patients,
      nor was retraction of bladder observed in any case of this series. CONCLUSION:
      This method is effective in the prevention of bladder cancer recurrence.
      Protection from light is not necessary during treatment.

PMID- 10920886
TI  - [The effect of antibody against vascular endothelial growth factor on tumor
      growth].
AB  - OBJECTIVE: Vascular endothelial growth factor (VEGF) is a very important factor
      in the process of angiogenesis, which is chosen as a target for experimental
      study of anticancer. METHODS: Anti-VEGF antibody was obtained from immunized
      rabbits and purified with affinity column. Morever, it was identified as
      neutralized antibody by Mile's assay. RESULTS: The anti-VEGF antibody was able to
      inhibit growth of S180 sarcoma in a dose-dependent manner, and the inhibition
      rate reached 41.0% with dose 200 micrograms per mouse per day. For human gastric
      cancer (MGC-803)-bearing nude mice, Anti-VEGF antibody inhibited tumor growth by
      76.2%. When anti-VEGF antibody was combined with 131I-3H11, a murine monoclonal
      antibody conjugated with 131I for treatment, only one of five nude mice developed
      tumor and 84.0% more inhibition of tumor growth was obtained in comparison with
      treatment by 131I-3H11 only. CONCLUSION: The anti-VEGF antibody may be
      potentially useful for clinical treatment of cancer.

PMID- 10920887
TI  - [Retroviral vector mediated gene transfer and expression of human GM-CSF in HL-60
      leukemic cells].
AB  - OBJECTIVE: To study the condition and possibility for introducing foreign gene
      into myeloid leukemic cells and gene therapy for malignant tumors in hematology.
      METHODS: With Lipofectin technique, N2A/CMV/hGM-CSF was transfected into
      packaging cell line PA317 and recombinant retrovirus were obtained. Then the
      human myeloid leukemic cells HL-60 were infected with recombinant retroviral
      supernatant. Positive cells were obtained through the neomycin analogue G418
      selection. RESULTS: Successful integration of GM-CSF gene into HL-60 cell genome
      was verified by PCR and Southern Blot, while no specific fragments were amplified
      by PCR test in HL-60 cells without being transferred or transferred with empty
      vector N2A. With measurement by GM-CSF dependent cell line TF-1, the level of GM
      CSF released by the GM-CSF gene modi-fied HL-60 cell line was 60-200 ng.ml-1.10(
      6).24 h-1, while the supernatant of HL-60 cells without being transferred or
      transferred with empty vector N2A. CONCLUSION: hGM-CSF gene mediated by
      retroviral vector can achieve efficient transfer and expression in HL-60 leukemic
      cells.

PMID- 10920888
TI  - [Alterations in metastatic properties of hepatocellular carcinoma cell following
      H-ras oncogene transfection].
AB  - OBJECTIVE: To demonstrate the relationship between H-ras oncogene and HCC
      metastasis. METHODS: Activated H-ras oncogenes were transfected into SMMC7721, a
      cell line derived from human hepatocellular carcinoma (HCC), by calcium phosphate
      transfection method. Some metastasis-related parameters were detected in vitro,
      including adhesion assay, migration assay, expresion of collagenase IV (cIVase)
      and EGFR. RESULTS: The abilities of H-ras-transfected cell clones in adhesion to
      laminin or fibronectin, migration, cIVase secretion increased markedly, and the
      expression of EGFR elerated moderately. More importantly, these alterations were
      consistently positive with the expression of p21, the protein product of H-ras
      oncogene. CONCLUSION: H-ras oncogene could induce the metastatic phenotype of HCC
      cell in vitro, therefore enhancing its metastatic potential.

PMID- 10920889
TI  - [Correlation between hypomethylation of c-myc and c-N-ras oncogenes and
      pathological changes in human hepatocellular carcinoma].
AB  - OBJECTIVE: To evaluate the molecular biological mechanism of human hepatocellular
      carcinoma--DNA methylation pattern of certain oncogenes. METHODS: Methylation
      patterns of c-myc, c-N-ras oncogenes in human hepatocellular carcinoma were
      studied by the Southern blot technique and HpaII/MspI restriction endonucleases.
      The pathological changes were also analyzed. RESULTS: The c-myc and c-N-ras
      oncogene fragments were hypomethylated in DNA samples derived from cancerous
      (30.3% and 60.1%) and adjacent paracancerous (12.1% and 30.3%) liver tissues.
      Hypomethylation of c-myc gene in multifocal type was significant as compared with
      unifocal type (P < 0.05). It is also found that c-N-ras gene hypomethylation had
      a strong correlation with tumor size (P < 0.01). CONCLUSION: The decrease of DNA
      methylation is present at the stage of liver carcinoma, and hypomethylation of c
      myc, c-N-ras genes is correlated with the tendency of infiltration and
      metastasis.

PMID- 10920890
TI  - [Assignment of a novel colorectal cancer-associated gene HSU17714 gene to human
      chromosome band 22q13 by in situ hybridization].
AB  - OBJECTIVE: To identify the chromosomal localization of novel colorectal cancer
      related gene HSU17714. METHODS: Enhanced fluorescence in situ hybridization
      technique was applied with tyramine as the enhancer. RESULTS: 80%(128/160)
      interphase and 60% (104/174) metaphase cells showed obvious hybridization signals
      of HSU17714. 85%(40/47) metaphase cells showed hybridization signals at 22q13 in
      the fluorescence R-banding assay. CONCLUSION: HSU17714 is assigned to human
      chromosome 22q13.

PMID- 10920891
TI  - [Chromosome marker--2q- during carcinogenesis and development of human lung
      cancer].
AB  - OBJECTIVE: To study the cytogengtic alterations during the development of human
      lung cancer and to clarify the genetic basis of lung cancer. METHODS: Using
      Fluorescence in situ Hybridization FISH, we have studied the chromosomal
      alterations of chromosome 2 and 3 in human bronchial epithelial cell line M, and
      12 primary non-small cell lung cancer (NSCLC) specimens. RESULTS: 2q- was found
      in the later passage of human bronchial epithelial cell line M, and 3 out of 7
      primary NSCLC specimens tested. 3p- being noted in five cases of 12 primary NSCLC
      patients examined was the first cytogenetic discovery and the most prominent
      abnormality in lung cancer. 2q- was rarely reported in human lung cancer before.
      But loss of heterozygosity by RFLP analysis for 2q had been reported in lung
      cancer. CONCLUSION: 2q- is also a common chromosome abnormality in human lung
      cancer. There would also be one or more putative tumor suppressor gene(s) on the
      long arm of chromosome 2. Loss of the gene(s) may contribute to the
      carcinogenesis of human non-small-cell lung cancer.

PMID- 10920892
TI  - [Modulation of invasiveness and invasion/metastasis-associated gene expression of
      a mouse mammary adenocarcinoma by interferons].
AB  - OBJECTIVE: To investigate the effects of IFNs on the in vitro invasiveness and
      the expression of several genes related to invasion and metastatic behavior of MA
      891 cells. METHODS: The invasiveness was assessed by penetration through a
      matrigel-coated filter. Cell surface antigen and mRNA levels were analyzed by
      flow cytometry and Northern blot respectively. RESULTS: IFN-gamma pretreatment
      increased the invasiveness of MA-891 (P < 0.01). Pretreatment with IFN-alpha
      decreased the invasiveness of cells, but it was not statistically significant.
      Cell surface ICAM-1 was not found on MA-891 cells even after treatment with IFN
      alpha, but was strongly induced after IFN-gamma treatment. Another adhesion
      molecule CD44v mRNA, absent on MA-891 cells, could not be induced to express by
      either IFN. Both 72,000 and 92,000 type IV collagenase mRNAs were detectable in
      MA-891 cells. The 72 kD-type IV collagenase expression was up-regulated by IFN
      gamma and IFN-alpha, but the levels of expression were significantly higher in
      cells treated with IFN-gamma than those treated with IFN-alpha. IFN-gamma and IFN
      alpha treatment had little or no effect on expression of the 92,000 type IV
      collagenase. Treatment with IFN-gamma had no effects on antimetastasis nm23 gene
      expression whereas treatment with IFN-alpha resulted in marked up-regulation of
      its expression. CONCLUSION: IFN-gamma and IFN-alpha differ in their effects on
      the expression of genes related to invasion and metastasis of MA-891 cells,
      thereby differentially modulating metastatic potential.

PMID- 10920893
TI  - [Mechanism and treatment of cancer cachexia in tumor-bearing mice].
AB  - OBJECTIVE: To evaluate the role of TNF-alpha in the development of cancer
      cachexia, and the effects of TNF-alpha antibody and high agglutinated
      staphylococcin (BM828) in the treatment of experimental cancer cachexia. METHODS:
      T739 mice bearing LA795 tumor were used as murine tumor cachexia model and also
      the T739 receiving TNF-alpha. The level of serum TNF-alpha was assayed by TNF
      alpha RIA in each group. Comparisons were made in the food intake and body weight
      of all the five groups including BM828 and TNF-alpha AB groups. RESULTS: Two
      weeks after being inoculated with LA795, the tumor-bearing mice developed
      significant anorexia and weight loss. The level of serum TNF-alpha in tumor
      bearing mice was significantly higher than that in the non-tumor bearing mice (P
      < 0.01). TNF-alpha administration to mice resulted also in marked anorexia and
      weight loss as in cancer cachexia. CONCLUSION: The results suggested that the
      mechanism of cachexia be correlated with TNF-alpha. BM828 and TNF-alpha AB have
      the potentiality of attenuating the development of cachexia in murine models.

PMID- 10920894
TI  - [Significance of endocrine cells and their hormones in colorectal cancer].
AB  - OBJECTIVE: To analyse the expression and clinical pathologic significance of
      endocrine cell (EC) and their hormones in colorectal cancer (CC). METHODS:
      Chromograin A (CGA) and five kinds of hormones in 117 cases of CC were detected
      by immunohistochemistry with 13 observed by electron microscopy. RESULTS: CGA
      positive cells (EC) occurred in 46 cases (39.3%). 69.2%(27/39) expressed more
      than one hormone. The lymph node metastasis rate (68.0%) in the EC-positive CC
      was higher than EC-negative CC (43.7%) (P < 0.05). The incidence of EC(+2) in CC
      with morderative and poor differentiated (25.5%) was higher than well
      differentiated (P < 0.05). EC-positive CC gave shorter survival. It's an
      independent factor for evaluating prognosis in CC. The expression of 5-HT, GLU,
      GAST and beta-HCG occurred more offen in tumor with moderate and poor
      differentiation giving poor prognosis (P < 0.05). Cancer cells containing
      endocrine granules were found in 8 cases of CC by electron microscopy. The two
      methods were comformable in 92.3%. CONCLUSION: EC-positive CC has poor
      histological differemtiation, giving rise to more lymph mode metastasis and poor
      prognosis. Some hormones secreted by EC could partly account for the growth and
      metastasis of CC.

PMID- 10920895
TI  - [4-acetamidophenyl retinoate (4-APR) inhibits reconstituted basement membrane
      invasion by tumor cells and its mechanism].
AB  - OBJECTIVE: To study the inhibitory effect of new retinoid 4-acetamidophenyl
      retinoate (4-APR) on the reconstituted basement membrane invasion by B16-F10
      mouse melanoma cells and its mechanism. METHODS: Reconstituted basement membrane
      invasion assay was used to evaluate invasive ability of cancer cells. Type IV
      collagenase was assessed by PAGE substrate zymography. TIMP-1 mRNA expression of
      human nasopharyngeal carcinoma CNE-2Z cell line was measured by dot blot
      analysis. Cell growth curve assay was used to examine the growth inhibitory
      effect of 4-APR on B16-F10 cells. RESULTS: 4-APR, at the concentrations of 10(-5)
      mol/L and 10(-6) mol/L, suppressed the reconstituted basement membrane invasion
      of B16-F10 mouse melanoma cells by 54.2%, 41.9% and reduced type IV collagenase
      activities in the serum-free supernatant of CNE-2Z cells. In addition, 4-APR
      inhibited B16-F10 cell adherence to laminin, fibronectin and Matrigel, and
      induced CNE-2Z cell TIMP-1 mRNA expression. CONCLUSION: Reconstituted basement
      membrane invasion of B16-F10 mouse melanoma cells was inhibited by 4-APR. The
      anti-invasion action of 4-APR might be associated with the suppression of tumor
      cell adhesion ability, the reduction of type IV collagenase activity in tumor
      cell culture supernatant and/or the induction of tumor cell TIMP-1 mRNA
      expression.

PMID- 10920896
TI  - [Clinical study on myxoma and chordoma in the skull base].
AB  - OBJECTIVE: The clinical manifestation, neuroimaging properties, and pathologic
      changes of myxoma and chordoma were studied. METHODS: Their neuroimaging
      properties and pathologic changes of myxoma 7 cases and chordoma 13 cases were
      analyzed. RESULTS: (1) Clinical manifestation: the injury of oculomotor nerve and
      exorbitism is dominant in myxoma, but the injury of posterior cranial nerves is
      dominant in chordomas. (2) Plain skull X-ray film: local irregular punctate
      calcification and osseous necrosis were common in myxoma. Clivus invasion
      moruloid calcification and cauliflower-like calcification are always seen in
      chordoma. (3) CT and MRI: Location of the tumor and their relations with the
      adjacent structure were clear. (4) Pathologic changes: Cells are punctately
      arranged in myxoma, and vesicularly arranged in chordoma. CONCLUSION: The
      clinical study of myxoma and chordoma is not only useful for their differiental
      diagnosis, but can provide valuable clues for their surgical approach as well.

PMID- 10920897
TI  - [Evaluation of enhanced CT examination in the differential diagnosis of local
      recurrence and postradiation fibrosis in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate enhanced CT examination in the differential diagnosis of
      local tumor recurrence and postradiation fibrosis when a mass appeared is
      observed after radiation therapy of carcinoma of nasopharynx. METHODS: 159 cases
      of nasopharyngeal carcinoma were examined by CT, including 37 cases of local
      recurrence(RT) after radiation therapy and 54 cases of postradiation fibrosis
      (RF) 68 cases of nasopharyngeal carcinoma (PT) before radiation therapy sened as
      comparison. Elscint sprint 2000 CT machine was used. The CT number of plain and
      enhanced examination of the mass appearing after radiation therapy were measured.
      Variance analysis was used as statistical management for CT number difference of
      different kinds of mass lesions before and after contrast enhancement. RESULTS:
      In the RT cases, the average CT number of the mass lesion for plain scan were
      50.40 +/- 8.10 Hu, and for enhanced scan it was 73.74 +/- 7.37 Hu. In the RF
      cases plain scan 48.62 +/- 10.15 Hu, enhanced scan 56.74 +/- 8.69 Hu, In the
      control cases (PT), the CT number in the plain scan of lesion was 48.32 +/- 9.20
      Hu, and 72.38 +/- 7.75 Hu in the enhanced examination. These measurement showed
      obvious enhancement of recurrence tumor. The CT number of contrast scan of RT and
      RF was obviousy different (P < 0.01). CONCLUSION: If a mass lesion appears after
      radiation therapy in carcinoma of nasopharyx, enhancement of the lesion in CT
      scan is an important criterion for differential diagnosis.

PMID- 10920898
TI  - [Ten-case report on primary cervical lymphoma].
AB  - OBJECTIVE AND METHODS: Clinical feature, treatment and prognosis of primary
      cervical lymphoma: are retrospectively analysied. RESULTS: The disease is rare,
      comprising about 0.9% of all primary cervical malignancies. The average age was
      43.6 years. Seven cases had history of familial carcinoma. The complaints:
      abnormal vaginal bleeding and/or vaginal discharge. The usual pattern of growth
      was endophytic or polypoid. By FIGO cervical cancer, staging system, there were
      8/10 stage I b, 1/10 stage II b and 1/10 stage IV. Histologically all were NHL, B
      cell lesions(7/10) were the diffuse, cleaved or cleaved-noncleaved cell type.
      Combination of surgery and chemotherapy were used for 9 of these 10 patients. The
      follow-up period was 3-66 months. Only one patient had relapse 41 months after
      the treatment while, others (9/10) survived with no evidence of the disease.
      CONCLUSION: The prognosis is favorable if cervical lymphoma is discovered early
      and treated properly.

PMID- 10920900
TI  - [Multivariate analysis on prognostic factors of non-Hodgkin's lymphoma].
AB  - OBJECTIVE: To predict the prognostic factors and to improve the response and
      survival in intermediate-grade and high-grade non-Hodgkin lymphoma (NHL).
      METHODS: 200 patients with intermediate-grade and high-grade NHL were treated
      with chemotherapy. A multivariate Cox model was used to analyse the prognostic
      factors that significantly affect the treatment outcome. The variables examined
      included: sex, age, clinic stage of disease, B symptoms, extranodal sites, bone
      marrow involvement, tumor bulk, performance status (ECOG) and malignancy grades.
      RESULTS: Multivariate analysis showed that performance status, the number of
      extranodal sites, pathologic malignancy grade and tumor bulk were significantly
      independent prognostic factors. These factors were put together to construct a
      prognostic index formula. The index partitioned the patients into low risk group
      (PI -2.43(-)-1.30), intermediate risk group (PI -1.29-1.0) and high risk group
      (PI > 1.0) giving 5-year survival rates of 76.0%, 21.6% and 7.4%, respectively.
      CONCLUSION: The prognostic index formula and subgroups could serve as a reference
      to distinguish patients requiring more intensive chemotherapy and autologous stem
      cell transplantation from those who should be treated with standard regimens in
      order to improve the prognosis.

PMID- 10920899
TI  - [Comparison of CHEP and CHOP chemotherapy in the management of non-Hodgkin's
      lymphoma].
AB  - OBJECTIVE: Therapeutic effect and toxicity of CHEP and CHOP chemotherapy in the
      treatment of non-Hodgkin's lymphoma (NHL) were compared. METHODS: From October
      1989 to June 1996, comparison of 52 NHL was carried out: CHEP (cyclophol
      sphamide, adriamycin, etoposide, prednisone) group-26 patients and
      CHOP(cyclophosphamide, adriamycin, vincristine, prednisone) group-26 patients.
      The responses and toxicities were compared by the chi 2 test. RESULTS: The CHEP
      group gave an overall response rate of 76.9%(20/26). In 10 untreated patients CR
      was observed in 7; The CHOP group gave an overall response rate of 65.4%(17/26).
      In 17 untreated patients CR was observed in 8(P > 0.05). Having been followed to
      the end of August, 1996, 16 patients in the CHEP group and 15 patients in the
      CHOP group were alive with respective median survivals 24(3-66) months and 20(2
      48) months. Among the untreated patients, the 1-year disease-free survival (DFS)
      rates of those who gave CR were 70.0% and 23.5% (P < 0.05). 2-5 year DFS rats
      were 30%, 20%, 20%, 20%, and 11.8%, 5.9%, 5.9%, orespectively. The toxic
      reactions were tolerable in both groups. CONCLUSION: In untreated NHL patients as
      treated with CHEP chemotherapy, 1-year DFS rate was superior to that of CHOP
      regimen (P < 0.05). Side toxicities were comparable in both groups, but no
      peripheral neuritis was observed in the CHEP group.

PMID- 10920901
TI  - [Different chemotherapy protocols for intermediate and high grade malignant non
      Hodgkin's lymphoma].
AB  - OBJECTIVE: To assess the optinums chemotherapeutic protocols for higher CR rate
      in the treatment of intermediate and high grade malignant non Hodgin's
      lyphoma(NHL). METHODS: Seventy-four patients with pathological intermediate and
      high grade malignant NHL were tried randomly with revised ProMACE
      CytaBOM(treatment group) and CHOP(control group). RESULTS: The CR rate was 56.8%
      in the treatment group and 35.0% in the control group (P > 0.05). In patients
      with high grade maliganat NHL, the CR rate of ProMACE-CytaBOM was 60.0% as
      compared with 32.0% of the CHOP (P < 0.05). Patients in both group suffered from
      similar side effects with tolerable bone marrow supression and gastric
      irritation. CONCLUSION: ProMACE-CytaBOM is a safe regimen with relative high CR
      rate for high grade malignant NHL, but further research is indicated for remote
      results.

PMID- 10920902
TI  - [Clinical evaluation of enantone in the treatment of prostate cancer].
AB  - OBJECTIVE: In order to improve the effect of hormone treatment for prostate
      cancer, a total of 17 such patients were treated with Enantone(chemical
      castration) from July 1990 to July 1992. METHODS: In the control group, 16
      evaluable patients who were followed for 3 to 5 years, PSA was determined with
      ELISA. Commercial kit was used for determination of T, LH and FSH. Prostate
      lesion and metastasis and patient's status was eximination in the follow-up.
      RESULTS: Enantone was ableto suppress plasma testosterone concentration to the
      condition of castration during treatment (P < 0.01). PSA and other markers also
      responded well. Significant improvement in performance status, micturition
      problems and general well-being was reported. CONCLUSION: The once a-month
      administration of Enantone combined with flutamide is effective in the management
      of advanced prostate cancer with acceptable side-effects.

PMID- 10920904
TI  - [Chest CT and its assessment of resectability in lung cancer].
AB  - OBJECTIVE: To evaluate chest CT and its relation to possible surgical resection
      in lung cancer patients. METHODS: Ninty-five patients who were diagnosed and
      confirmed as having lung cancers by surgery and pathology were divided into three
      groups: (1) Radical resection group; (2) Palliative resection group and (3)
      Thoractomy group. The diameter of the tumor, the proximity to mediastinum and/or
      the hilum and the invasion of their lymph nodes were measured. Meanwhile, the
      changes in the mediastinum and thoracic cavity on the chest CT were noted in
      these three groups. RESULTS: The diameter of the tumor in each group was 4.10 +/-
      1.75, 3.90 +/- 1.20, 5.20 +/- 3.66 (cm, mean +/- s, P > 0.05). The proximity to
      the mediastinum and/or the hilum and the invasion of their lymph nodes was 2.68
      +/- 1.60, 4.02 +/- 1.56, 4.85 +/- 3.28 (cm, mean +/- s, P < 0.01, P < 0.05). The
      characteristic change in the thoractomy group is deformity in the lymph nodes in
      the mediastinum and hilum. CONCLUSION: There is no obvious relation between the
      diameter of the lumg tumor and surgical resection, but the proximity to the
      mediastinum and/or the hilum and the invasion of their lymph nodes is an
      important factor. It is possible to perform a radical resection when its contact
      is less than 2.68 +/- 1.60 cm. Obvious deformity of the mediastinal structures
      and the hilum is a contraindication for lung cancer surgery.

PMID- 10920903
TI  - [Cox proportion hazard model multivariate analysis of prognosis of 1,484 axillary
      node-negative breast cancer patients].
AB  - OBJECTIVE: To study the prognosis of axillary node-negative breast cancer
      patients. METHODS: The data were analyzed in 1,484 consecutive axillary node
      negative breast cancer patients. Twenty-two individual variables were evaluated
      statistically using the cumulative survival rate by the computer's Cox
      multivariate analysis model. RESULTS: Menopausal status, times of pregnancy,
      duration before diagnosis, pregnancy-associated, tumor size, intramammary lymph
      node, postoperative radiotherapy and postoperative adjuvant tamoxifen therapy
      were independent predictors of prognosis. CONCLUSION: Parts of high risk group
      among axillary node-negative breast cancer patients could be identified by
      clinical parameters. Postoperative radiotherapy or ovarian ablation was not
      indicated for axillary node-negative breast cancer patients. Tamoxifen as
      postoperative adjuvant therapy should not be restricted to postmenopausal or ER
      positive patients. The selection of high risk patients with axillary node
      negative breast cancer who should receive adjuvant chemotherapy remains to be
      investigated at present.

PMID- 10920905
TI  - [Long-term results of intravesical N-CWS instillation to prevent recurrence after
      surgery for bladder cancer].
AB  - OBJECTIVE: To evaluate the long term results of intravesical nocardia rubre cell
      wall skeleton instillation to prevent recurrence after surgery for bladder
      cancer. METHODS: A randomized and placedo-controlled trial on intravesical N-CWS
      instillation versus mitomycin-C(MMC) therapy for recurrence prevention in
      postopenative bladder cancer patients was carried out. RESULTS: Fourty-five
      patients were treated with N-CWS with 39 followed for 12 to 60 months. Thirteen
      patients developed recurrence. The 1-year tumor free survival rate was 87.2% and
      that at 5 years was 66.7%. Thirty patients as treated with MMC serving as
      controll with 25 followed for the same duration, twelve patients developed
      recurrence. The 1-year tumor free survival rate was 84% and that at 5 years was
      52%. The results indicate that N-CWS gave better results with rare and milder
      side effects. CONCLUSION: N-CWS is believed to be one of the effective drugs in
      preventing bladder cancer recurrence after surgery.

PMID- 10920907
TI  - [Research on characteristics of mortality spectrum and type composition of
      malignant tumors in China].

PMID- 10920906
TI  - [Management and prognosis of patients with locally recurrent soft tissue
      sarcomas].
AB  - OBJECTIVE: The results and prognositic factors in treating locally recurrent soft
      tissue sarcoma (STS) of the extremities and trunk were identified. METHODS: The
      clinical, pathologic, and therapeutic characteristics of 96 STS patients were
      investigated using univariate and multivariate analyses. Seventy-six patients
      (79.2%) had high grade sarcoma and 20 patients (20.8%) had low grade sarcoma.
      Operative procedures were wide excision (surgical margin > or = 2 cm) in 66,
      local excision (surgical margin < 2 cm) in 6, and amputation in 24 patients.
      Adjuvant radiotherapy and chemotherapy was administered in 24 and 36 patients
      respectively. RESULTS: After reoperation of the recurrent tumor, the 5-year local
      control and overall survival rates were 70.1% and 59.1%, respectively. High
      grade, large size, and tumor in the upper extremities were associated with
      decreased overall survival. CONCLUSION: The authors emphasize that the initial
      management of primary STS should be adequate and suggest that safty margin of >
      or = 2 cm should be adhered to. In patients with local recurrence only, the
      overall survival may not be adversely affected if the recurrent lesion is
      properly treated. Investigations of more effective multimodality therapy needs to
      be done.

PMID- 10920908
TI  - [The effect of IL-2 and IL-3 gene therapy in mice on immunological recovery
      receiving high dose chemotherapy].
AB  - OBJECTIVE: To investigate the effect of Ad-IL-2 and Ad-IL-3 on immunological
      recovery. METHODS: The Ad-IL-2 and/or Ad-IL-3 were i.p. injected into C57BL/6
      mice having received high dose cyclophosphamide (200 mg/kg) 24 hours before. The
      number and cytotoxicity, Ia antigen expression of peritoneal macrophages, the
      proliferation and NK cell activity of splenic cells were observed. RESULTS: After
      i.p. injection with Ad-IL-3, the number, cytotoxicity and Ia antigen expression
      of peritoneal macrophagee were increased. After i.p. injection with Ad-IL-2, the
      proliferation and NK cell activity of splenic cells were significantly augmented.
      As i.p. injection with Ad-IL-2 and Ad-IL-3 simultaneously, both the peritoneal
      macrophages and splenic cells were activated. CONCLUSION: Intraperitoneal
      injection of Ad-IL-2 and Ad-IL-3 can promote immune recovery after high dose
      chemotherapy.

PMID- 10920909
TI  - [An experimental study of angiogenesis inhibitor TNP-470 on tumor growth and
      metastasis of Lewis lung carcinoma].
AB  - OBJECTIVE: The inhibition effect of angiogenesis inhibitor TNP-470 on tumor
      growth and metastasis was studied using Lewis lung carcinoma. METHODS: Lewis lung
      carcinoma cells(2.4 x 10(6)/mouse) were inoculated subcutaneously to 20 mice,
      they were randomized into 2 groups. From the 2nd day, the treated group was given
      40 mg/kg of TNP-470 s.c. q.o.d. (8 times) and the control group was given vehicle
      only (3% ethanol). On the 22nd day, the weight of the subcutanous tumors and the
      lung metastasis rates of the 2 groups were detected. The results were analysed by
      Student-t and chi 2 test. RESULTS: The tumor weight of the control and treated
      group was 3.77 +/- 1.05 g and 1.98 +/- 0.96 g, respectively (P = 0.0009). The
      lung metastasis rate of the control and treated group was 80%(8/10) and
      30%(3/10), respectively (P = 0.03). CONCLUSION: These results suggest that the
      angiogenesis inhibitor TNP-470 has a strong inhibitory effect both on growth of
      the primary tumor and metastasis of Lewis lung carcinoma.

PMID- 10920910
TI  - [Possible significance of novel DNA fragments frequently deleted from tumor cell
      lines of human esophageal cancer].
AB  - OBJECTIVE: To disclose the genetic susceptibility and carcinogenesis mechanism of
      esophageal cancer (EC) through finding out tumor suppressor genes. METHODS:
      Twenty EC tissues paired with adjacent normal mucosa and three high-risk EC
      families were analysed by PCR and Southern blot with DNA probes (12H2, 33B2, and
      33B3) frequently deleted from EC cell lines. RESULTS: In surgical samples, the
      deletion frequency of the fragment 12H2 was highest, i.e. 61% in EC tissues and
      22% in adjacent mucosa. The rate of tumor metastasis to lymph nodes was 45%. For
      the fragment 33B2, they were 30%, 10% and 50%, respectively. But only 20%, 10%
      and 25% were of the fragment 33B3. No genetic changes were found in the three
      high-risk EC families for 12H2 and 33B3. The deletion of 33B2 was seen in the
      proband of one family. CONCLUSION: The fragments 12H2, 33B2 and 33B3 may be
      candidates of tumor suppressor genes correlative with progression and metastasis
      of esophageal cancer.

PMID- 10920911
TI  - [Nuclear matrix protein pattern in human hepatocellular carcinoma].
AB  - OBJECTIVE: To compare nuclear matrix proteins of normal liver with those of
      hepatocellular carcinoma (HCC) to see whether there are HCC-specific proteins.
      METHODS: Using high resolution two-dimensional polyacrylamide gel
      electrophoresis, the nuclear matrix proteins of 3 normal livers and 8 HCC were
      compared. RESULTS: There was a high degree of similarity between nuclear proteins
      of normal liver and those of HCC. Four HCC-specific nuclear matrix proteins were
      identified. Among them, one protein(Mr: 62,000; pI: 5.3) appeared in all tumor
      samples. The other three proteins appeared in most of the 8 HCC cases. These
      proteins were not detected in 3 normal livers. CONCLUSION: There are HCC-specific
      nuclear matrix proteins which may be related to the etiology and pathogenesis of
      HCC.

PMID- 10920912
TI  - [Immunohistochemical study of c-erbB-2 and p53 protein in breast papillomatosis
      and its malignant transformation].
AB  - OBJECTIVE: To evaluate the levels of c-erbB-2 and p53 protein in different stages
      of papillomatosis of breast and its malignant transformation and value for early
      diagnosis. METHODS: Levels of c-erbB-2 and p53 protein were detected by
      immunohistochemistry in 184 paraffin-embeded blocks. RESULTS: c-erbB-2 protein
      expression was seen in all stages of papillomatosis with different degrees of
      proliferation and in tissues undergone malignant transformation. The rate of
      overexpression increased with the degree of proliferation. The p53 protein
      expression was not found in papillomatosis with mild to severe proliferation. It
      was only overexpressed in 3.5% of carcinoma arising from papillomatosis, but
      increased to 25% when invasion occurred. CONCLUSION: c-erbB-2 assay may be
      helpful for detection of early malignant change of the highly proliferative
      papillomatosis, especially when histopathological evidence of malignancy is still
      lacking. p53 protein is of no significant diagnostic value in these lesions.

PMID- 10920913
TI  - [Studies on programmed cell death induced by amsacrine and expression of bcl-2 in
      leukemia cell lines].
AB  - OBJECTIVE: To study programmed cell death (PCD) in two human acute myelocytic
      leukemia cell lines in different differentiated phases, NB4(AML3) and HL
      60(AML2). METHODS: PCD cells were detected microscopically, DNA
      electrophoretically and flow cytometrically. Expression of bcl-2 gene was
      examined by immunohistochemistry staining. RESULTS: Exposed to 1-20 micrograms/ml
      m-AMSA for 6-12 h, morphological changes in NB4 cells were more evident than in
      HL-60 cells. Internucleosomal fragmentation(DNA ladders) was more marked in NB4
      than in HL-60 cells. Flow cytometric analysis indicated that the number of PCD
      cells in NB4 cells was more than that in HL-60 cells. HL-60 cells had
      significantly higher mean bcl-2 level than NB4 cells. CONCLUSION: The high bcl-2
      level in HL-60 cells may be related to their comparatively low sensitivity to m
      AMSA-induced PCD.

PMID- 10920914
TI  - [Effect of ascorbate on the permeation and photosensitizing activity of
      hematoporphyrin derivative (HPD) in tumor].
AB  - OBJECTIVE: To determine the depth of permeation and concentration of HPD in tumor
      tissue which had been immersed in HPD in the presence and absence of ascorbic
      acid, and to examine its photosensitizing effect. METHODS: Solid S-180 sarcoma of
      1 cm3 in size was excised from tumor-bearing mice and immersed in HPD (PsD-007) 1
      mg/ml normal saline (group I), or HPD (PsD-007) 1 mg/ml plus ascorbic acid 20
      mg/ml normal saline (group II) for 1 hr. For comparison, HPD (PsD-007) 10 mg/kg
      was injected intravenously to mice bearing tumor of similar size and the tumor
      was excised 24 hr later(group III). RESULTS: When the tumors were cross-sectioned
      and UV (370 nm) irradiated, red fluorescence was mainly at the periphery of
      tumors that had been immersed in HPD whereas the fluorescence was weaker and more
      evenly distributed in tumors of mice that had received HPD i.v. Similar features
      were observed under fluorescence microscope in frozen sections of identically
      treated tumors. The concentration of PsD-007 (microgram/g) and malondialdehyde
      (nmol/L) in the tumor homogenates was higher in tumors that had been immersed in
      PsD-007 plus ascorbate than in tumors immersed in PsD-007 alone. Tumors of mice
      that had received PsD-007 i.v. had the lowest concentration of both PsD-007 and
      malondialdehyde. CONCLUSION: Ascorbate facilitates permeation of HPD into tumor
      and enhances the photo-dynamic effect of HPD.

PMID- 10920916
TI  - [Phase III clinical studies with ondansetron (Qilu) in the prophylaxis of nausea
      and vomiting induced by cisplatin].
AB  - OBJECTIVE: To further evaluate the clinical usefulness of ondensetron(OND,
      supplied by Qilu Pharmaceutical Company) with modified regime in the prevention
      of cisplatin (DDP)-induced nausea and vomiting. METHODS: A total of 773 patients
      were enrolled in a multicenter cooperative study. Of them, 330 patients were
      given i.v. OND 8 mg once or twice a day and 443 patients were given i.v. OND 8 mg
      plus dexamethasone(DXM) 10 mg once a day during the therapeutic period of DDP,
      followed by OND 4 mg orally twice a day for two days after DDP treatment.
      RESULTS: Effective control of acute nausea was achieved in 86.7% and 94.8% of the
      patients receiving OND alone and OND plus DXM, respectively(P < 0.001). The mean
      frequency of vomiting was 0.9 times in OND and 0.4 times in OND plus DXM(P <
      0.01). Total control of delayed vomiting (day 2-5) was comparable in both groups.
      Complete inhibition of vomiting (CR rate) was more frequently observed in males
      than in females. Adverse effects were identical and well tolerated. CONCLUSION:
      OND with modified regimen is effective in the control of DDP-induced vomiting. It
      is more effective when OND and DXM are given than OND given alone.

PMID- 10920915
TI  - [Suicide gene therapy for glioma using HSV-tk/GCV system].
AB  - OBJECTIVE: To establish a suicide gene therapy system HSV-tk/GCV for glioma
      treatment in vitro as well as in vivo and test its efficacy. METHODS: C6 rat
      glioma cells were infected with recombinant retrovirus containing HSV-tk gene.
      Following selection the C6/tk cell line which stably expressed tk was cloned. The
      sensitivities of C6/tk cells to several nucleoside analogues, such as GCV, BVdU,
      ACV, were compaired by the growth inhibition studies. Antitumor effects were also
      observed after GCV treatment in nude mice bearing tumors derived from C6/tk
      cells. RESULTS: The growth inhibition studies showed that GCV was the most
      efficient prodrug, and C6/tk cells were highly sensitive to GCV, with an IC50 <
      0.2 mumol/L, being 500-fold less than that in tk-negative C6 cells. In vivo
      studies showed similar results. Significant tumor inhibition was found in the
      treatment group. CONCLUSION: Tumor cells expressing HSV-tk gene can be eradicated
      by administration of GCV in vitro as well as in vivo.

PMID- 10920917
TI  - [Colored Doppler ultrasound-guided fine-needle aspiration biopsy of portal vein
      thrombosis: value in diagnosis and assessment of therapeutic efficacy for portal
      vein thrombosis].
AB  - OBJECTIVE: To investigate the value of colored Doppler ultrasound-guided fine
      needle aspiration(FNA) biopsy of portal vien thrombosis(PVT) in diagnosis and
      assessment of therapeutic efficacy for PVT. METHODS: Cytologic findings from 25
      portal vien thrombosis patients who underwent FNA were reviewed before and after
      hepatic arterial chemo-embolization(HAE) and portal vien chemotherapy. RESULTS:
      1. Biopsy specimens sufficient for histologic analysis were obtained in all cases
      (100%). No complications resulted from this procedure. 2. The blood flow within
      the portal vien with thrombosis could be detected by colored Doppler systems in
      25 cases before the patients accepted the treatment. The proliferation and a
      trabecular cellular arrangement presented in all the cell blocks. Of the 25
      cases, 4 (16.0%) demonstrated necrosis of the tumor thrombi and the disappearance
      of blood flow within portal vein thrombi three weeks after the treatment. Among
      the 4, 2 were followed-up clinically and underwent second stage resection. 21
      (84.0%) cases had no significant change in portal vein thrombosis pathologically
      and ultrasonically after the treatment. CONCLUSION: Colored Doppler ultrasound
      guided FNA biopsy of portal vein thrombi is a safe, accurate, sampling-reliable
      biopsy technique.

PMID- 10920918
TI  - [The effect of estrogen receptor level on the prognosis of the elderly breast
      cancer patients].
AB  - OBJECTIVE: To evaluate the effect of estrogen receptor (ER) on the prognosis of
      the elderly female breast cancer patients and the guidance for their post
      operation therapy. METHODS: 134 cases of the elderly female breast cancer
      patients (> or = 60 year-old) were divided into two groups depending on their ER
      level. Kaplan-Meier method was used to estimate disease-free servival (DFS) rate
      from the date of surgery. RESULTS: There were 88 patients in ER (+) group and 46
      patients in ER (-) group. The medium follow-up of the ER (+) and the ER (-) group
      was 92.5 and 85.5 months, respectively. The incidence of recurrence and
      metastasis was 20.5% (18/88) in the ER (+) group and 41.3% (19/46) in the ER (-)
      group (P < 0.02). CONCLUSION: Estrogen receptor is a reference factor to predict
      prognosis of breast cancer in elderly patients.

PMID- 10920919
TI  - [Analysis of high frequency X-ray images in 43 cases of breast cancer].
AB  - OBJECTIVE: To analyse a series of breast cancer images in high frequency X-ray
      for more accurate diagnosis of breast cancer. METHODS: Forty three high frequency
      X-ray images of breast cancer surgically confirmed were comprehensively analyzed.
      RESULTS: Of the 43 breast cancer cases, 42 were primary breast cancers and one
      secondary. Tumor mass was present in 38 cases, with burrs in 26. Malignant
      calcification was found in 13 cases, and structural derangement in 21 cases.
      There were 30 cases with abnormal blood vessels, and 7 cases with thick skins.
      Ductal and lymph drainage features were seen in 9 cases. There were 5 cases
      showing ox horn sign. The high frequency X-ray diagnosis of breast cancer
      conformed with pathologic diagnosis in 95.6% of the cases. CONCLUSION: The
      advantages of high frequency X-ray are its extremely high clarity and good
      contrast. Pictures can be taken form various axises which help detect occult and
      tiny cancer.

PMID- 10920921
TI  - [B-ultrasonographic diagnosis of emergency complications in lung cancer
      patients].
AB  - OBJECTIVES: To assess the value of B-ultrasonography in the diagnosis and
      treatment of emergency complications in lung cancer patients. METHODS: Thirty
      five patients with lung cancer who suffered from emergency conditions were
      examined with B-ultrasonography. Of the 35 cases, 5 had superior vena caval
      syndrome due to compression by a centrally located tumor mass in the right upper
      lobe; 10 had moderate to large accumulation of fluid in the pericardium with
      cardiac tamponade; 2 had metastasis to the myocardium and pericardium with acute
      hemorrhagic pericardial effusion; 20 had massive pleural effusion. The
      ultrasonographic features of these complications were described. Patients with
      pericardial or pleural effusion received intervention treatment with Elemen
      emulsion under B-ultrasound guidance. RESULTS: Combined with systemic
      chemotherapy, in 4-week period, complications were temporarily ameliorated in
      82.8% and became clinically stable in 8.5% of the cases. Treatment was of no
      effect in 8.5%. CONCLUSION: B-ultrasonography is of value in the diagnosis of
      emergency complications of lung cancer and is of help to guide intervention
      treatment.

PMID- 10920920
TI  - [Peri-operative death in patients undergone lung cancer resection].
AB  - OBJECTIVE: To ascertain the causes of peri-operative death in patients with lung
      cancer. METHODS: Five cases died in the peri-operative period in 174 lung cancer
      patients undergone resection were analyzed. RESULTS: Two cases died from
      pulmonary edema and/or atelectasis; one died from acute myocardial infarction and
      ventricular fibrillation; one had sudden death immediately after withdrawal of
      endotracheal tube; the other one died of brain matastasis and multiple organ
      failure. CONCLUSION: Cardio-pulmonary complications are the major causes of peri
      operative death in lung cancer patients. Appropriate preventive meassures should
      be taken to reduce operative mortality.

PMID- 10920922
TI  - [Immunohistochemical study of p53, c-erbB-2 and nm23 proteins in human gastric
      cancer].
AB  - OBJECTIVE: To evaluate p53, c-erbB-2 and nm23 oncoproteins in diagnosis of
      gastric cancer. METHODS: The expression of p53, c-erbB-2 and nm23 oncoproteins
      was detected immunohistochemically in 141 surgically resected specimens and 93
      endoscopic biopsy specimens of gastric cancer. RESULTS: The positive rate of p53,
      c-erbB-2 and nm23 immunoreactivity was 45.8-56.3%, 18.3-31.2% and 72.9%-81.3%
      respectively. No immunoreactivity was observed in the tumor-adjacent normal
      mucosa and non-tumor biopsy specimens. The presence of c-erbB-2 was correlated
      with the size of tumor, grade of tumor differentiation and Lanren classification.
      Patients with c-erbB-2 positive tumor had lower 5-year survival rate. The
      expression of nm23 was negatively correlated with the depth of invasion, and
      lymphnode metastasis. The positive rates of p53, c-erbB-2 and nm23 had no
      statistical difference between biopsy and resected specimens. CONCLUSION:
      Determination of p53, c-erbB-2 and nm23 oncoproteins immunohistochemically might
      be useful in the diagnosis and differential diagnosis, clinical staging, and
      predicting prognosis of gastric cancer.

PMID- 10920924
TI  - [Intrathoracic gastric function after esophagectomy for patients with esophageal
      cancer].
AB  - OBJECTIVE: To reveal the physiological changes of intrathoracic stomach after
      esophagectomy and find ways to improve patients' digestive function. METHODS: In
      twenty preoperative and 41 postoperative patients, the physiologic functions of
      stomach were studied and compared with radioisotope technique, pressure
      measurement, 24-hour pH monitoring and gastroscopy. RESULTS: The emptying of
      semisolid food from the intrathoracic stomach was much delayed (P < 0.01); its
      acid secretion was decreased in the early postoperative period (P < 0.01) but it
      restored to normal one year later. Fasting serum gastrin level was higher (P <
      0.01) in the early postoperative period but showed a partial restoration one year
      later. The high pressure zone at anastomosis helped prevent gastroesophageal
      reflux. High incidence of gastritis was found in intrathoracic stomach and this
      may be related to gastric stasis. CONCLUSION: Performing scarf telescoping
      anastomosis and pyloraplasty, giving a certain amount of pepsin, diluted
      hydrochloric acid and anti-gastrin drug to early postoperative patients should be
      beneficial to reducing the symptoms and normalizing patients' digestive function.

PMID- 10920923
TI  - [Study of the relationship between the expression of Ki-67 antigen and the
      pathobiological behaviours of stomach cancer].
AB  - OBJECTIVE: To evaluate the relationship between the expression of Ki-67 antigen
      and the pathobiological behaviours of stomach cancers especially their distant
      metastases. METHODS: 56 stomach cancer specimens routinely fixed in formalin and
      embeded in paraffin (FFEP) were studied by immunohistochemical method. RESULTS:
      Expression of Ki-67 antigen was significantly related to the distant metastases
      to liver, ovary and adrenal gland (P < 0.005); but not related to the
      histological type, growth pattern, depth of invasion, histological
      differentiation and the metastases to local lymph nodes (P > 0.05). Furthermore,
      the Ki-67 expression was significantly related to the DNA anueploid pattern and
      the expression of p53 protein, both of which are closely related to poor
      prognosis. CONCLUSION: Overexpression of Ki-67 can be used as an objective marker
      of the proliferative activity for predicting prognosis of stomach cancer and to
      foretell the high-risk of metastasis of distant organs.

PMID- 10920925
TI  - [An analysis of causes of death in 329 emergency cancer patients].
AB  - OBJECTIVE: To analyze the causes of death in cancer patients. METHODS: In
      collection of 2,167 cancer cases coming to the emergency clinic, the causes of
      death were analyzed in 329 cases. RESULTS: Of the 329 cases, 25.8% (85/329) was
      due to the cancer growth itself while 59.9% (197/329) was resulted from
      complications. Thirty-seven cases (11.2%) died within 12 h in the emergency
      clinic. Most of the deaths were seen in patients with cancer of the lung, stomach
      and liver. Infection, respiratory failure, shock, hemorrhage and cardiac attack
      were the causes of death. The first two causes accounted for 36.2% and 32.5% of
      the total deaths in this series, respectively. CONCLUSION: Complications are the
      major causees of death. The importance of their proper prevention needs to be
      emphysized.

PMID- 10920926
TI  - [The long-term therapeutic results of chemotherapy combined with radiotherapy in
      advanced nasopharyngeal carcinoma].
AB  - OBJECTIVE: To evaluate the effect of chemothrapy combined with radiotherapy in
      advanced nasopharyngeal carcinoma (NPC). METHODS: From Dec. 1989 to Dec. 1990, 76
      patients with locally advanced NPC (stage III or IV) were treated with 3 cycles
      of cisplatin [PDD, 20 mg.(m2)-1.day-1, i.v. on days 1-5] and 5-Fluorouracil (5
      Fu, 700 mg.(m2)-1.day-1 by continuous i.v. infusion on days 1-5 followed shortly
      thereafter by radiotherapy. Eighty-six patients treated with radiotherapy alone
      in 1989 were taken as control. The methods and time/dose schedule of radiotherapy
      were similar in the two groups. RESULTS: The response rate to chemotherapy was
      89.3% [complete response (CR) 18.4%]. The overall 5-year survival was 48.7% in
      the combined treatment group and 33.6% in the control group (P > 0.05). The 5
      year survival in the combined treatment group was 44.1% and 39.5%, in patients
      with T2N3 and T2-4N3 and 21.6% and 20.4% in the control group, respectively (P <
      0.05). CONCLUSION: This prospective study demonstrates that PDD/5-Fu chemotherapy
      followed by radiotherapy can improve 5-year survival in patients with T2-4N3
      nasopharyngeal carcinoma.

PMID- 10920927
TI  - [Multivariate prognostic analysis of carcinoma of the gastric cardia and
      comparative study of different resections].
AB  - OBJECTIVE: To evaluate the clinical characteristics and prognostic factors for
      long-term survival of patients with cancer of gastric cardia. METHODS: Logistic
      regression, log-rank test were used to analyze survival and evaluate the results
      of different resection procedures. RESULTS: Of the 263 patients, the male to
      female ratio was 8.4:1, the average age of female patients was younger than that
      of male patients. Sex, depth of invasion and lymph node involvement were
      prognostic factors of long-term survival. The extent of gastric resection and
      lymph node dissection, and pre-operative chemotherapy did not significantly
      affect survival. Higher frequency of postoperative complications was observed in
      patients received extended dissections, but did not affect survival. However, for
      patients in stage III N0-1, extended dissection resulted in longer survival than
      those received routine radical resection. CONCLUSION: Cancer of the gastric
      cardia has its own clinical characteristics. The surgical procedures should be
      adjusted according to the prognostic factors. For relatively early cases,
      extended dissection is recommanded.

PMID- 10920928
TI  - [Establishment of a human hepatocellular carcinoma (HCC) cell line with high
      metastatic potential (MHCC97) and its biological characteristics].
AB  - OBJECTIVE: To establish and characterize a human hepatocellular carcinoma cell
      line with high metastatic potential derived from a subcutaneous xenograft of
      metastatic human HCC in nude mice (LCI-D20). METHODS: Single-cell suspension
      collected by tearing tumor tissues with forceps was transferred to the tissue
      culture flasks for culture in vitro in medium DMEM supplemented with 10% human
      group AB serum. Cytogenetic studies were performed on this cell line using flow
      cytometry and chromosome G-banding. AFP of theprimary xenografts and lung
      metastatic lesions was detected by using ABC immunohistochemistry. The rates of
      its tumorigenicity and metastasis in nude mice were evaluated. RESULTS: The
      MHCC97 cells showed typical epithelial appearance. Upon subcutaneous or
      intrahepatic inoculation in nude mice, the xenograft grew and metastasized to the
      lungs. The metastatic rate was 100%. The cancer cells of lung metastatic foci
      were AFP positive. Aberrant chromosomes i(1)(q) and der(4) (pter-->q35::?) were
      its chromosome markers. CONCLUSION: The MHCC97 cell line maintained the biologic
      characteristics as its original xenografts. The presence of the reported
      chromosomal aberrations may be related to carcinogenesis and progression of HCC.

PMID- 10920929
TI  - [Chemoprevention of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine-induced
      carcinogen-DNA adducts by Chinese cabbage in rats].
AB  - OBJECTIVES: To examine the preventive effect of Chinese cabbage (Brassica
      chinensis) against colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5
      b]pyridine (PhIP)-induced PhIP-DNA adduct formation in rats and its possible
      mechanism. METHODS: Sprague-Dawley rats were maintained for 10 days on lab chow
      or chow containing 20% (w/w) freeze-dried cabbage powder prior to administration
      of a single dose of PhIP (10 mg/kg) by oral gavage. Rats were sacrificed at 20 h
      after PhIP treatment and PhIP-DNA adducts in the colon, heart, lung, and liver
      were analyzed using 32P-postlabeling technique. Levels of hepatic cytochrome P450
      (CYP) 1A1 and 1A2, as indicated by 7-ethoxyresorufin O-deethylase and 7
      methoxyresorufin O-demethylase activity, and cytosolic glutathione S-transferases
      (GST) towards CDNB in the liver, lung and colon mucosa were measured. RESULTS:
      Rats pre-treated with Chinese cabbage and given a single dose of PhIP had reduced
      levels of PhIP-DNA adducts in the colon, heart, lung and liver, with an
      inhibition rate of 82.3, 60.6, 48.4 and 48.9%, respectively (P < 0.01). Enzyme
      assays revealed that both CYP1A1 and 1A2 were induced by cabbage, but the
      induction was preferential for CYP1A1 over 1A2 (80.6% vs 50.2%). GST activity
      towards CDNB in the liver and lung, but not colon, was also significantly induced
      by the cabbage. CONCLUSION: The results indicate a preventive effect of Chinese
      cabbage against PhIP-initiated carcinogenesis in rats and the mechanism is likely
      to involve induction of detoxification enzymes.

PMID- 10920930
TI  - [Study on the status of methylation of Rb gene promoter in human esophageal
      cancer and effect of NMBzA on Rb gene promoter in monkey esophageal epithelium].
AB  - OBJECTIVE: To elucidate the cause of abnormal Rb expression in esophageal cancer
      (EC). METHODS: Methylation of Rb gene promoter was examined with restriction
      endonuclease digestion and PCR amplification. RESULTS: Of the 30 specimens of EC,
      10 (33.3%) had Msp I type hypermethylation of the Rb gene promoter while 12
      (40.0%) had Hpa II type hypermethylation and one had both type of
      hypermethylation. In monkey fed with a single dose of NMBzA (30 mg/kg) on day 0,
      increasing hypermethylation of both types of the Rb gene promoter in esophageal
      epithelium was found on day 1, 2 and 3 but reduced on day 5. CONCLUSION: These
      data suggest that abnoromal expression of Rb gene may be related to
      hypermethylation of its promoter and carcinogen NMBzA can induce such
      hypermethylation in monkey esophageal epithelium.

PMID- 10920931
TI  - [Correlation study of spontaneous apoptosis, PCNA, and p53 in esophageal squamous
      cell carcinoma].
AB  - OBJECTIVE: To investigate the inter-relationships among spontaneous apoptosis,
      proliferative activity and p53 mutation in esophageal squamous-cell carcinoma.
      METHODS: In 30 previondy untreated patients with esophageal squamous-cell
      carcinoma, tissues were examined for apoptosis by in-situ TUNEL, PCNA by
      immunohistochemistry, p53 mutation by PCR-SSCP and immunohistochemistry. The
      number of apoptotic cells per 10 low-power microseopic fields was taken as the
      apoptotic index. RESULTS: Apoptotic index of cells with high proliferative
      activity was significantly higher than that of cells with low proliferative
      activity (P < 0.05). In tumors with p53 gene mutation, apoptotic index of cells
      with high proliferative activity and low proliferative activity was significantly
      different (P < 0.05). No significant differences were observed in apoptotic index
      in tumors positive and negative for p53 mutation as examined by PCR-SSCP or
      immunohistochemistry (P > 0.05). CONCLUSION: In squamous-cell carcinoma of the
      esophagus, cells with high proliferative activity are apt to undergo spontaneous
      apoptosis.

PMID- 10920932
TI  - [Adenovirus-mediated p53 gene therapy of human laryngeal cancer].
AB  - OBJECTIVE: To explore the potential use of p53 in gene therapy for laryngeal
      cancer. METHODS: A human laryngeal cancer cell line Hep-2 was used. Recombinant
      cytomegalovirus-promoted adeno-viruses containing human wild-type p53 cDNA was
      transiently introduced into Hep-2 cells in vitro and injected into tumor nodules
      in vivo. The growth of Hep-2 cells in vitro and established s.c. squamous
      carcinoma nodules in nude mice was examined. RESULTS: The transduction efficiency
      of Hep-2 cell line was 100% at > or = 100 MOI. The p53 protein expression peaked
      on day 2 after infection and lasted far 5 days. Cell growth was greatly
      suppressed. In vivo studies, Ad5CMV-p53 transfestion in vitro inhibited
      tumorigenicity of Hep-2 cells in nude mice. Intra-tumoral injection of Ad5CMV-p53
      significantly inhibited established s.c. implanted xenograft. CONCLUSION:
      Transfection of wild-type p53 gene via Ad5CMV-p53 is a potential approach to the
      therapy of laryngeal cancer.

PMID- 10920933
TI  - [Therapeutic effect of EGFR antisense cDNA on rat C6 gliomas in vivo].
AB  - OBJECTIVE: To study the therapeutic effect of EGFR antisense cDNA on rat C6
      glioma in vivo and find out the feasibility of using EGFR gene as a target in
      gene therapy of gliomas. METHOD: Wild type C6 cells and C6 cells transfected with
      EGFR antisense cDNA were implanted stereotaxically to the caudate nucleus of
      right cerebrum of Wistar rats (control and transfected group, 8 and 6 rats
      respectively), and rats with cerebral tumor foci were treated with EGFR antisense
      cDNA mediated by Lipofectamine (treated group, 9 rats). The general
      manifestation, survival time, MRI features, histopathological change,
      proliferation activity and apoptosis of the gliomas in each group of rats were
      observed. RESULTS: The mean survival time of control animals was 17.3 days. That
      of the 6 transfected and 6 treated animals was significantly prolonged. Four
      transfected and 3 treated rats were killed on day 28-90 after implantation for
      histopathological examination. The surviving time of the 4 remaining rats (1
      transfected and 3 treated rats) was over 200 days. MRI demonstrated a distinct
      cerebral tumor in control rats, but the tumor foci were not found in the
      transfected rats and disappeared almost completely in the treated rats. The
      cerebral gliomas of rats after treatment with EGFR antisense cDNA showed decrease
      in proliferation activity and apoptosis. CONCLUSION: The results of EGFR
      antisense cDNA in treatment of rat C6 glioma is encouraging. EGFR gene can be
      used as the target of gene therapy for malignant gliomas.

PMID- 10920935
TI  - [Telomerase activity in human primary endometrial carcinoma].
AB  - OBJECTIVE: To investigate the possible relationship between telomerase expression
      and progression of endometrial carcinoma. METHODS: Thirty-four primary
      endometrial carcinoma and 6 normal endometrial tissue specimens were examined by
      means of telomeric repeat amplification protocol (TRAP) assay for telomerase
      activity. RESULTS: Of 34 endometrial cancer specimens, 28 (82.4%) showed
      telomerase activity, whereas 1 of 6 (16.7%) benign endometrial tissues exhibited
      telomerase activity. CONCLUSION: Telomerase expression might contribute to the
      progression of endometrial carcinoma and could be used as its tumor marker.

PMID- 10920934
TI  - [Study on nuclear matrix protein in leukemia cells].
AB  - OBJECTIVE: To compare the composition of nuclear matrix proteins (NMP) between
      leukemia cells and normal bone marrow cells. METHODS: NMP was isolated by high
      salt extration and identified by SDS-PAGE and western blotting. RESULTS: Increase
      in NMP was demonstrated in acute and chronic myelogenous leukemic cells as well
      as in the blast phase of chronic leukemia. On SDS-PAGE, NMPs with molecular
      weight different from what were seen in normal bone marrow cells were present in
      both acute and chronic myelogenous leukemias. CONCLUSION: Marked changes of NMP,
      not only in contents but also in compositions, exist in leukemic cells compared
      with normal bone marrow cells. NMP may serve as a target of chemotherapeutic
      drugs against leukemia.

PMID- 10920936
TI  - [Detection of telomerase activity in bronchoscopic brush-off cells in lung cancer
      patients].
AB  - OBJECTIVE: To investigate the diagnostic significance of the detection of
      telomerase activity in the exfoliated cells obtained from fiberobronchoscopic
      brushing. METHODS: The techniques of TRAP-PCR-ELISA and TRAP-silver staining were
      employed to detecte telomerase activity in 57 cases with pulmonary diseases.
      RESULTS: Telomerase activity in the lesion side of lung cancer patients (N = 23)
      was significantly higher than that in the contralateral side of the same patient
      (P < 0.05), and in patients with pneumonia (P < 0.05). Positive rate of
      telomerase activity detection in lung cancer patients (91.3%) was significantely
      higher than that of cytological examination (52.3%, P < 0.05). In 83.3% of the
      cases examined, exfoliated cells showing cytological dysplasia were found to be
      telomerase activity positive. CONCLUSION: Detection of telomerase activity in the
      exfoliated cells obtained from fiberobronchoscopic brushing may be an effective
      and sensitive method in the diagnosis of pulmonary malignant diseases.

PMID- 10920937
TI  - [Telomerase activity in liver cancer and the adjacent tissue].
AB  - OBJECTIVE: To investigate the possibility of using telomerase as a tumor marker
      for human primary hepatocellular carcinomas (HCC). METHODS: Human liver
      specimens, comprising 33 HCC and adjacent peritumoral tissues, 4 hepatic
      metastases and the adjacent peritumoral tissues, 6 benign liver lesions and 6
      normal liver tissues, were examined for telomerase activity by TRAP assay based
      on PCR. RESULTS: Thirty of 33 HCC and 9 of 33 adjacent tissue specimens were
      positive for telomerase activity with a positive rate of 90.9% and 27.3%,
      respectively. Four hepatic metastatic cancer and 2 adjacent tissues were
      positive. Telomerase activity was negative in 6 nomal liver tissues and 5 of 6
      benign liver lesions. There was no correlation between the clinical stage of HCC
      and their telomerase activity. CONCLUSION: Positive telomerase activity occurs in
      the majority of HCC examined. It can be used as a tumor marker in the diagnosis
      of HCC.

PMID- 10920938
TI  - [Clinical evaluation of several tumor markers in the diagnosis of primary hepatic
      cancer].
AB  - OBJECTIVE: To evaluate the practical significance of alphafetoprotein(AFP), alpha
      L-fucosidase(AFu), gamma-glutamyltransferase(GGT), sialic acid(SA) and
      carcinoembryonic antigen(CEA) in the diagnosis of primary hepatic cancer(PHC).
      METHODS: AFP, AFu, GGT, SA and CEA in the serum were studied in 67 patients with
      PHC, 8 with hepatic metastasis of gastrointestinal cancer, 89 with benign liver
      diseases and in 131 controls without liver diseases. RESULTS: According to
      statistics, the sensitivity of AFP, AFu, GGT, SA and CEA in the diagnosis of PHC
      was 65.4%, 70.8%, 34.8%, 60.2% and 36.4% repectively; their specificity was
      92.6%, 98.1%, 87.1%, 94.5% and 77.8% respectively. CEA in hepatic metastasis of
      gastrointestinal cancer was higher than that in the other groups of patients.
      Simultaneous detection of AFP, AFu GGT and CEA gave a diagnostic sensitivity and
      specificity in PHC of 81.4% and 91.6% respectively. CONCLUSION: AFP and AFu are
      superior to GGT, SA and CEA in the diagnosis of PHC; simultaneous detection of
      AFP, AFu, GGT and SA might increase the diagnositic sensitivity and specificity
      of PHC. CEA was less helpful in the diagnosis of PHC, but might be used to
      differentiate PHC from hepatic metastasis of gastrointestinal cancer.

PMID- 10920939
TI  - [Clinico-pathological significance of microvessel density and VEGF expression in
      primary liver cancer].
AB  - OBJECTIVE: To evulate the clinico-pathological singnificance of intratumoral
      microvessel density (MVD) and VEGF expression in primary liver cancer (PLC).
      METHODS: A retrospective study including 63 postoperative small PLC (diameter < 5
      cm) patients was done. One group of 29 patients developed recurrence or
      metastasis within 2 years. The other group of 34 patients had no evidence of
      recurrence or metastasis within 2 years. Three PLC sections were taken from each
      patient, one for H. E. staining, the other two for VEGF and vascular endothelial
      cell immunohistochemical staining, respectively. MVD was counted by endothelial
      cells which were highlighted by Bio-UEA-I. RESULTS: The MVD in patients with
      cancer recurrence or metastasis was (49.6 +/- 29.7) significantly greater than
      the other group (22.7 +/- 28.2) (P < 0.01). The positive rate of VEGF in cancer
      recurrence group was 86.2% (25/29), being significantly higher than the other
      group (47.1%) (P < 0.01). The stage of the tumor, the positive rate of satellite
      nodules and portal vein embolus were all significantly different between the 2
      groups. CONCLUSION: Besides tumor stage, satellite nodules and portal vein
      embolus, the MVD and VEGF expression are also of prognostic significance.

PMID- 10920940
TI  - [Manifestation and diagnostic value of MR imaging in meningeal carcinomatosis].
AB  - OBJECTIVE: To analyze the patterns of MRI manifestation, and to investigate the
      value of MRI in diagnosis of meningeal carcinomatosis. METHODS: Twenty three
      cases with meningeal carcinomtosis were analyzed. All cases had pre- and post-
      contrast MR imagings, typical clinical symptoms and/or positive CSF examination.
      RESULTS: Of the 23 cases, 22 had abnormal post-contrast meningeal enhancement.
      The remaining case had hydrocephalus without any enhancement. There were four
      abnormal MRI patterns: (1)total meningeal enhancement, (2) smooth or nodular
      enhancement of parts of the meninge, (3)subependymal enhancement,
      (4)hydrocephalus only. CONCLUSION: MRI is an important assistant method in
      diagnosis of meningeal carcinomatosis. Post-contrast MRI is mandatory.

PMID- 10920941
TI  - [Diagnostic value of p53 protein examination in lung cancer through preoperative
      fibro-optic bronchoscope brushing and biospy].
AB  - OBJECTIVE: To study the expression of p53 protein in lung cancer and benign
      pulmonary diseases through preoperative fibro-optic bronchoscope brushing and
      biospy as an approach to early diagnosis of lung cancer and to explore
      correlation between the expression of the gene product and metastatic involvement
      of hilar or mediastial lymph nodes. METHODS: Using a monoclonal antibody against
      p53, the expression of p53 protein was determined by immunocyto-histochemical
      techniques. RESULTS: Positive staining of p53 protein of cells obtained form
      bronchoscopic brushing and biospy was 33.3% (12/36) and 47.2% (17/36)
      respectively in lung cancer patients. There was 61.1% (22/36) positive staining
      of cells harvested by brushing plus biospy in lung cancer. No correlation between
      p53 protein expression and cell differentiation, histologic type or pTNM staging.
      No p53 expression was observed in benign pulmonary diseases. CONCLUSION: p53
      protein expression in cells collected from bronchoscopic brushing and biopsy may
      be useful in the diagnosis of lung cancer.

PMID- 10920942
TI  - [Proximal bronchial invasion of lung cancer: a clinicopathological study].
AB  - OBJECTIVE: To investigate the characteristics of proximal bronchial invasion of
      lung cancer of different types. METHODS: Proximal bronchus of 151 operatively
      resected specimens of hilar type lung cancer was selected for cross-sectional
      pathological study. Forty one specimens were obtained from total pulmonectomy,
      and 110 from pulmonary lobectomy. RESULTS: Evidence showed that the direct
      invasion of tumour cells through the submucosal layer or multiple layers was the
      major form of lung cancer spread; 96.6% of the cancerous invasion occurred at the
      proximal bronchial wall less than 1.5 cm apart from the margin of the cancer. The
      extension of invasion was correlated with the histopathologic type of cancer,
      mode of invasion and TNM classification(pT, pN). Besides, the invasion in the
      bronchial wall by metastatic lymph nodes was also an important way for the cancer
      spread. CONCLUSION: In order to achieve radical removal of tumor, it is
      imperative to keep a distance of 1.5 cm or more between the excision margin of
      the bronchus and the tumor, and to completely resect the hilar and mediastinal
      lymph nodes.

PMID- 10920943
TI  - [Randomized controlled study of leucomax (recombinant human granulocyte
      macrophage colony stimulating factor, rhGM-CSF) in the treatment of cancer
      chemotherapy-induced leucopenia].
AB  - OBJECTIVE: To evaluate leucomax (rhGM-CSF) in prevention and treatment of
      leucopenia and neutropenia induced by chemotherapy in cancer patients. METHODS: A
      multicenter, randomized, matched and cross-over clinical trial of the effect of
      leucomax on leucopenia and neutropenia induced by combination chemotherapy in
      cancer patients was conducted. Fifty seven enrolled patients were randomized into
      AB group and BA group. Each patient received two cycles of treatment. In group
      AB, combination chemotherapy and leucomax were used in the first cycle and
      combination chemotherapy alone was used in the second cycle, while vice versa in
      group BA. In 2 patients, the study was stopped due to leucomax adverse reactions.
      Fifty five patients were eligible for analysis of clinical efficacy. RESULTS:
      Leucomax significantly increased the number of total white blood cell count and
      absolute neutrophil count at the nadir, decreased the incidence of leucopenia and
      neutropenia and shortened the time period of leucopenia and neutropenia induced
      by chemotherapy. Leucomax also resulted in quicker recovery of leucopenia and
      neutropenia. Leucomax ensured the scheduled chemotherapy. The main adverse
      reactions with mild to moderate fever, pain at the injection site, bone pain,
      myalgia, asthenia and skin rash were generally tolerable. CONCLUSION: Leucomax is
      a valuable adjunct in cancer chemotherapy.

PMID- 10920944
TI  - [Esophago-gastric mucosal anastomosis with staples after resection of cancer of
      the esophagus and gastric cardia].
AB  - OBJECTIVE: To delve an effective method to prevent anastomotic leakage and
      stenosis. METHODS: Staples were used to carry out mucosal anastomosis between the
      esophagus and stomach. RESULTS: Four hundred thirty four patients were so
      treated. The morbidity rate was 9.3% and the mortality rate was 1.4%. No leakage
      or stenosis was found in this series. CONCLUSION: Using staples to perfonm
      mucosal anastomotis has the advantages of being simple and safe. Besides
      prevention of leakage and stenosis, sufficient length of resection of the
      esophagus helps reduce the likelihood of residual stump cancer recurrence.

PMID- 10920945
TI  - [Percutaneous transfemoral arterial implantation of drug delivery system for
      arterial infusion therapy of advanced primary hepatic carcinoma].
AB  - OBJECTIVE: To study the efficiency of arterial infusion chemotherapy via drug
      delivery system (DDS) for advanced primary hepatic carcinoma. METHODS: Hepatic
      arterial infusion chemotherapy was performed in 82 cases of primary hepatic
      carcinoma with no indication for operation or transarterial embolism treatment.
      The patients were divided into 2 group as follows: (1) Group A: 42 patients were
      treated intra-arterially once every 1 or 2 weeks via implanted DDS. (2) Group B:
      40 patients were treated through one bolus arterial infusion chemotherapy, once
      every month. RESULTS: The response rate (CR + PR) was 38.1% and 15.0%
      respectively in group A and B (P < 0.05); the 0.5-, 1- and 2- year survival rate
      was 61.9%, 28.6% and 9.5% respectively in group A, but 20%, 5%, 0% respectively
      in group B (P < 0.01); Liver, biliary, gastrointestinal and bone marrow toxicity
      in group A patients was greatly lower than those in group B patients. CONCLUSION:
      Intermittent arterial infusion chemotherapy via DDS significantly improves
      survival and quality of life in patients with advanced primary hepatic carcinoma.

PMID- 10920946
TI  - [Malignant mixed mesodermal tumors of the ovary: a clinical analysis of 12
      cases].
AB  - OBJECTIVE: To explore the clinical characteristics, treatment and prognostic
      factors of patients with malignant mixed mesodermal tumors of the ovary (MMMTO).
      METHODS: Clinical data of 12 patients with MMMTO between 1983-1997 were reviewed
      retrospectively. The median age of the patients was 50.7 years. According to FIGO
      staging system (1985), there were 4 cases in stage II, 6 in stage III and 1 in
      stage IV. Staging was unclear in the remaining case. Heterologous and homologous
      elements were present in the primary ovarian tumors in 4 and 8 of the 12
      patients, respectively. All patients received cytoreductive surgery. Eleven of
      them received postoperative chemotherapy and 3 of these eleven patients received
      additional radiotherapy of pelvic field. RESULTS: The median survival of this
      group of 12 patients was 24 months. The 2- and 5-year survival rate was 33.3%
      (4/12) and 8.33% (1/12), respectively. The 2-year survival rate of stage II and
      III was 50% and 33.3% respectively. One patent in stage IV died within 1 year.
      Four of the 8 patients with homologous histology survived over 2 years while all
      the 4 cases with heterologous histology died within 2 years. Five of the 11
      patients (45.5%) received combination therapy died within 1 year while 1 patient
      treated with surgery alone died within 6 months. CONCLUSIONS: The prognosis of
      MMMTO is rather poor. Surgery combined with chemotherapy and/or radiotherapy
      seems to be a better choice of approach. The histological tpyes of tumor and
      stage of the disease are related to prognosis.

PMID- 10920947
TI  - [Surgical treatment of perplexing renal cell carcinoma].
AB  - OBJECTIVE: To summarize the experience of surgical treatment of perplexing renal
      cell carcinoma in order to increase survival rate. METHODS: From 1987 through
      1996, 20 patients with perplexing renal cell carcinoma were surgically treated.
      There were 3 patients in stage I, 9 in stage II, and 8 in stage III. The
      operative proceduce was described and the follow-up results were analysed.
      RESULTS: Among 20 patients, 18 were evaluable. The 1-, 3-, 5-year survival rate
      was 100%, 91.7% and 75% for stage I-II; 87.5%, 62.5% and 37.5% for stage III,
      respectively. CONCLUSION: Radical nephrectomy is still effective for the patients
      with perplexing renal cell carcinoma.

PMID- 10920948
TI  - [Recurrent urothelial cancer after resection of ureteral carcinoma].
AB  - OBJECTIVE: To prevent and treat recurrent urothelial cancer after resection of
      ureteral carcinoma, recurrence-associated factors and their features were
      analyzed. METHODS: Thirty five cases of ureteral cancer were studied
      retrospectively. RESULTS: There were 16 cases of recurrent bladder cancer among
      32 cases after kidney-ureter and partial bladder removal. Bladder cancer recurred
      in 10 of 14 cases (71.4%) with multiorgan urothelial cancers. Six out of 18 cases
      with single ureteral cancer had recurrent cancer in the bladder. In 5 of the 6
      cases, the primary tumor was located at the lower ureter. None of the 4 cases in
      grade I had tumor recurrence while there were 16 cases of recurrent bladder
      cancer in 28 cases in grade II-III. There was one recurrent bladder cancer in 6
      cases in stage T1 within 2 years after operation. Among 26 cases in stage T2-T3,
      10 cases of recurrent bladder cancer occurred in 2 years. After 2 years, 5
      recurrent cases were in stage T1-T2. There were 2 recurrent urothelial carcinomas
      in 3 cases whose tumors were removed by local resection. The time of recurrence
      was 3 months to 6.5 years (average 1.86 years). Of 16 cases with recurrent
      urothelial cancer, 3 were alive for more than 3 years after operation. Of 8 cases
      without recurrence 6 survived for more than 3 years. CONCLUSION: Recurrent
      urothelial cancer after resection of ureteral cancer occurs more frequently when
      the neoplasm is located in the lower ureter, involving more than one organ, with
      high-grade cell differentiation and high invasiveness. Prognosis of recurrent
      urothelial cancer is poor. Regular cystoscopic check-up is helpful to find the
      recurrence.

PMID- 10920949
TI  - [A clinical report of high-dose epirubicin combined with cyclophosphamide and
      fluorouracil for advanced breast cancer].
AB  - OBJECTIVE: To evaluate safety and efficacy of high-dose epirubicin combined with
      cyclophosphamide and fluorouracil for advanced breast cancer. METHODS: Thirty two
      cases with stage III and IV breast cancer were treated with epirubicin (EPI) 90
      110 mg/m2, cyclophosphamide (CTX) 600 mg/m2 and 5-fluorouracil (5-Fu) 900 mg/m2
      every 21 days. The therapeutic effect was compared with that in patients treated
      with low-dose EPI(50 mg/m2). RESULTS: The response rate (RR) in patients treated
      with high-dose EPI was 71.9% (CR = 4, PR = 19) which was significantly better
      than that in the low-dose EPI-treated patients (CR = 2, PR = 5). The therapeutic
      effect was slightly better in patients initially diagnosed than in patients in
      recurrence (RR: 80% vs 68.2%) the median remission and surriving peroid was 7.4
      months and 12.5 months, respectively. The major side effect was leukopenia. Mild
      to moderate GI tract side effects were obsevved. There was no significant
      cardiotoxicity. CONCLUSION: High-dose EPI combined with CTX, 5-Fu is a safe and
      effective regimen for patients with advanced breast cancer worthy of further
      clinical trial.

PMID- 10920950
TI  - [Construction and expression of ScFv from anti-human gastric cancer McAb 3H11].
AB  - OBJECTIVE: To construct single chain antibody (ScFv) from anti-gastric cancer
      McAb 3H11. METHODS: Phage display technology was used to construct ScFv library
      from 3H11 hybridoma cells. Site-directed mutagenesis was used to resume the N
      terminal sequences of 3H11 ScFv. RESULTS: The library was screened against human
      gastric cancer cells MGC803 but no positive clone was obtained. Then, a random
      mutated ScFv library was constructed by error-prone PCR method, and panning
      selection was performed. Again the identification of positive clone was failed.
      Finally the N-terminal sequences of ScFv variable region was resumed to 3H11
      original sequences by site-directed mutagenesis via PCR, and the expressed ScFv
      in bacterial culture supernatant showed binding activity to gastric cancer cells.
      CONCLUSION: The N-terminal of the variable region introduced by PCR primers may
      seriously affect binding activity of the antibody.

PMID- 10920951
TI  - [8-chloro-adenosine induced apoptosis in various human tumor cell lines].
AB  - OBJECTIVE: To study the effect of 8-Chloro-adenosine (8CA) on tumor cell growth
      and apoptosis. METHODS: Tumor and normal cell lines were treated with 8CA at
      different concentrations and cell growth was analysed by MTT assay. Cell
      apoptosis was evaluated by light microscopy, flow cytometry and chromosome DNA
      fragmentation. RESULTS: Treatment with 8CA at 10 mumol/L remarkably inhibited
      tumor cell growth. HL-60 promyelocytic leukemia cell line was more sensitive to
      8CA than MGc-803 gastric mucoid adenocarcinoma cell line. NIH3T3 cells were
      relatively resistant to 8CA. The IC50 of HL-60 and MGc-803 cells was 1.2 mumol/L
      and 1.8 mumol/L, respectively, while that of NIH3T3 cells was 12 mumol/L. Further
      study showed that 8CA induced HL-60 and MGc-803 cell death characterized by
      apoptotic phenotypes, DNA content changes and chromosome DNA fragmentation.
      CONCLUSION: 8CA is a potential agent for tumor chemotherapy.

PMID- 10920952
TI  - [High frequency mutation of p53 gene in human gastric cancer and precancerous
      lesions].
AB  - OBJECTIVE: To determine the frequency and type of p53 gene mutation with the
      progression of human gastric carcinogenesis. METHODS: Single strand conformation
      polymorphism (SSCP) and DNA sequencing were performed on 56 biopsied tissues,
      including gastric cancer (n = 23), dysplasia (Dys, n = 16) and intestinal
      metaplasia (IM, n = 17). RESULTS: p53 gene mutation was detected in 60.1% of
      cancer, 31.3% of Dys and 11.8% of IM. Mutations covered exon 5-8 without hot
      spot. GC-->AT transitions (30.4%) and GC-->TA transversions (26.1%) were the
      major patterns of p53 mutation. Missense (73.9%) and frame shift mutations
      covered 86.9% of all mutations. CONCLUSION: In the process of human gastric
      carcinogenesis, multiple factors are involved in p53 gene mutations. The mutation
      rate increases with the progression of malignant changes in the gastric mucosa.
      Missense and frame shift mutations are possibly the major cause of p53
      inactivation.

PMID- 10920953
TI  - [Genetic polymorphisms of cytochrome P450 2E1 and glutathione S-transferase P1
      and susceptibility to esophageal cancer].
AB  - OBJECTIVES: To study the association between genetic polymorphisms of cytochrome
      P4502E1 (CYP2E1) and/or glutathione S-transferase P1 (GSTP1) and susceptibility
      to esophageal cancer. METHODS: Genotyping of CYP2E1 and GSTP1 was performed using
      PCR-based RFLP analysis on DNA isolated from surgically removed esophageal
      tissues or scraped esophageal epithelium from cancer cases (n = 45), severe
      epithelial hyperplasia cases (n = 45), and normal controls (n = 45). RESULTS: The
      variant genotypes (c1/c2 and c2/c2) detected by RsaI digestion was found in 17%
      of epithelial hyperplasia cases, 20.0% of esophageal cancer cases and 55.6% of
      controls, with the differences being statistically significant (P < 0.001).
      Subjects carrying wild-type genotype of CYP2E1 had more than 5-fold risk for
      developing severe epithelial hyperplasia (odds ratio, OR = 5.78; 95% confidence
      interval, CI = 2.2-15.2) and esophageal cancer (OR = 5.00; 95% CI = 2.0-12.8). No
      association with the risk of severe epithelial hyperplasia and esophageal cancer
      was observed for the DraI polymorphism of CYP2E1 or for the Awl26I polymorphism
      of GSTP1. CONCLUSION: CYP2E1 is a genetic susceptibility factor involved in the
      early events for esophageal carcinogenesis.

PMID- 10920954
TI  - [Liver metastasis models of human colo-rectal carcinoma established in nude mice
      by orthotopic transplantation and their biologic characteristics].
AB  - OBJECTIVES: To establish a liver metastasis models of human colorectal carcinomas
      in nude mice. METHODS: Orthotopic transplantation of histologically intact colo
      rectal cancer tissues from patients into colo-rectal mucosa of nude mice.
      Tumorgenicity, invasion, metastasis and morphological characteristics of the
      transplanted tumors were studied by light microscopy, electron microscopy and
      immunuhistochemistry. RESULTS: Liver metastasis models of human colon carcinoma
      (HCA-HMN-1) and human rectal carcinoma (HRA-HMN-2) were established after
      screening from 34 colorectal carcinomas. They had been passaged in vivo for 18
      and 21 gererations respectively. There were lymphatic, hematogenous, and
      implanting metastases. CEA secretion was maintained after transplantation. The
      primary and liver metastatic tumors were similar to the original human carcinoma
      in histopathological and ultrastructural features, DNA content and chromosomal
      karyotype. CONCLUSION: The liver metastasis models provide useful tools for the
      study of mechanism of metastasis and its treatment of human colo-rectal cancer.

PMID- 10920955
TI  - [Insulin-like growth factor-I upregulates the growth stimulatory effect of
      epidermal growth factor on HCE16/3 cells].
AB  - OBJECTIVES: To examine the role of insulin-like growth factor-I (IGF-I) in growth
      and gene expression of human papillomavirus (HPV) type 16 DNA-immortalized human
      cervical epithelial cells (HCE16/3 cells). METHODS: The growth and gene
      expression of HCE16/3 cells treated with IGF-I and epidermal growth factor (EGF)
      were examined by flow cytometry, soft-agarose assay and RT-PCR analysis. RESULTS:
      Physiological concentration of IGF-I had little effect on proliferation of
      HCE16/3 cells in serum-free and growth factor-free medium but supraphysiological
      concentration of IGF-I stimulated moderate proliferation of HCE16/3 cells. EGF
      stimulated proliferation of HCE16/3 cells at physiological concentration. The
      stimulatory effect was stronger when combined with IGF-I than EGF alone.
      Furthermore, the combined use of EGF and IGF-I could induce colony formation of
      HCE16/3 cells in soft agarose. The expression of HPV 16 E7 gene in HCE16/3 cells
      was not altered by growth factors in RT-PCR analysis. CONCLUSION: IGF-I is a weak
      regulator of HCE16/3 cells but it enhances the growth stimulatory effect of EGF
      on HCE16/3 cells.

PMID- 10920956
TI  - [The predominant expression of Th2 type cytokines in human tumor cells].
AB  - OBJECTIVE: To observe the expression of Th1 versus Th2 type cytokines in human
      tumor cells. METHODS: The gene expression of Th1/Th2 cytokines in human tumor
      cells was detected by RT-PCR and RNA dot hybridization using IL-2 and IFN gamma
      as Th1 type cytokine genes, IL-4, IL-10 and IL-13 as Th2 type cytokine genes.
      RESULTS: There were predominant expressions of Th2 type cytokines in 20 different
      human tumor cell lines including 11 solid tumor and 9 hematogenous tumor cells.
      CONCLUSION: Predominant expression of Th2 type cytokines by tumor cells may be
      related to the evasion of tumor cells from immune surveillance.

PMID- 10920957
TI  - [Antitumor effect of combined therapy with adenovirus-mediated CD suicide gene
      and interleukin 2 gene transfer and its immunological mechanism].
AB  - OBJECTIVE: Adenovirus harboring E. coli cytosine deaminase gene(AdCD) and
      adenovirus harboring interleukin 2 gene (AdIL-2) were used for the combined
      treatment of established tumors in vivo. METHODS: C57BL/6 mice were inoculated
      with B16F10 melanoma cells and 3 days later received at the tumor site injections
      of AdCD and/or AdIL-2 followed by i.p. injection of 5-fluorocytosine (5-Fc) 300
      mg/kg per day for 10 days. RESULTS: Mice received combined therapy developed
      tumors more slowly and survived much longer when compared with mice treated with
      AdCD/5-Fc, AdIL-2, control adenovirus AdlacZ/5-FC, or PBS. To investigate the
      immunological mechanism of the antitumor effects of the combined treatment it was
      found to induce enhanced natural killer cell activity and specific cytotoxic T
      cell activity. FACS analysis demonstrated that AdIL-2/AdCD/5-Fc therapy increased
      the expression of H-2Kb and B7-1 on freshly isolated tumor cells. The CD4+ and
      CD8+ T cell infiltration in the tumor increased significantly. CONCLUSION:
      Transfer of CD suicide gene plus 5-Fc combined with transfer of IL-2 gene
      synergistically inhibits the growth of melanoma in mice. Besides the cytotoxic
      effect of 5-Fc, specific and non-specific antitumor immunity might be responsible
      for the therapeutic effect. The combined therapy might have therapeutic
      potentials for human cancer.

PMID- 10920958
TI  - [Relationship between extracellular matrix and progressive growth of malignant
      tumor].
AB  - OBJECTIVE: To explore the role of extracellular matrix proteins in tumor cell
      invasion and metastasis. METHODS: Mouse pulmonary adenocarcinoma cell line LA795
      and human nasopharyngeal carcinoma cell line CNE-2Z were implanted subcutaneously
      and under the renal capsule in T739 and nude mice, respectively. At different
      time intervals, expression of fibronectin(FN), laminin(LN) and type IV
      collagen(IV C) in the tumor extracellular matrix and in tumor adjacent tissues
      was examined by indirect immunoperoxidase and immunofluorescence techniques. In
      addition, various in vitro methods (random migration of tumor cells in agarose
      droplet, growth of tumor cell colonies in soft agar, dot blotting, etc.) were
      used to analyse the effect of exogenous LN, FN or IV C. RESULTS: As tumor grew,
      the expression of FN, LN or IV C increased and presented different distribution
      patterns. Exogenous FN, LN and IV C enhanced the mobility of tumor cells and the
      growth of the tumor cell colonies. CONCLUSION: The distribution difference and
      the changes in synthesis and degradation of the extracellular matrix proteins are
      valuable in predicting the biologic behaviour. Tumor implanted under the renal
      capsule of mice offers a better experimental model to study the relationship
      between extracellular matrix and tumor cell invasion.

PMID- 10920959
TI  - [Studies of loss of heterozygosity(LOH) in Chinese human gastric cancer tissues].
AB  - OBJECTIVE: To identify the LOH frequency in Chinese gastric cancer samples and
      locate lost region of gastric cancer-related tumor suppressor gene. METHODS:
      Thirty microsatellite markers were used to examine 42 cases of tumor-normal
      paired gastric cancer tissues for LOH on all chromosomes (except Y) using
      polymerase chain reaction(PCR). RESULTS: The total frequency of LOH in 42 gastric
      cancer was 27.7%. High frequencies of LOH (> or = 40%) were observed at loci
      D3S1067, D3S1577, D6S430, D15S205, D17S945, and D5S407, D2S136, D2S147, D13S175,
      D14S68, D8S279 loci had LOH frequency > or = 30%. Significantly more LOH cases
      were observed in the poorly differentiated type and the signet-cell type than in
      well differentiated type of gastric cancers (P = 0.00699 and 0.0001). The
      incidence of LOH in signet-cell cancer was even significantly higher than that in
      poorly differentiated gastric carcinomas(P = 0.0019). LOH was not found in 4
      cases with well differentiated gastric cancer. CONCLUSION: The most common LOH
      occurred at D3S1577, D3S1067, D5S407, D6S430, D8S279, D15S205 and D17S945 might
      imply the existence of potential tumor suppressor genes of gastric cancer.

PMID- 10920960
TI  - [Radiation-induced apoptosis of two nasopharyngeal carcinoma cell lines].
AB  - OBJECTIVE: To study apoptosis induced by radiation in two nasopharyngeal
      carcinoma (NPC) cell lines, CNE and CNE-2. METHODS: Hoechst 33342 staining,
      immunocytochemical staining, RT-PCR, DNA dot blotting and Southern blotting were
      used to identify apoptosis. RESULTS: A single dose of X-irradiation resulted in
      apoptosis, the apoptotic index (AI) was time- and dose-dependent. Different
      apoptotic responses existed in the two cell lines. Immunocytochemical staining
      showed that bcl-2 protein was strongly positive in CNE but negetive in CNE-2.
      However, RT-PCR revealed p53 mRNA in CNE-2 but not in CNE. p53 and bcl-2 genes
      were both present in the two cell lines as shown by DNA blotting, but the 2.8 kb
      fragment of the p53 gene was much lower than the 5.6 Kb fragment in CNE which was
      clearly shown in Southern hybridization, suggestive of partial deletion of p53
      gene in CNE. CONCLUSION: Apoptotic response to radiation is different in 2 NPC
      cell lines. CNE is more radio-resistant than CNE-2. Overexpression of bcl-2
      protein and partial deletion of p53 gene may explain their difference in radio
      sensitivity.

PMID- 10920961
TI  - [Molecular cloning of a novel human lung cancer-associated antigen cDNA].
AB  - OBJECTIVE: To clone the gene of human lung cancer-associated antigen. METHODS:
      The human lung squamous carcinoma cell line L-78 cDNA expression library was
      constructed with lambda gt 11 Sfi-Not directional cloning vector and screened
      with the anti-human lung cancer McAb ALT-04. The cDNA clone named hlc-14 was
      sequenced and further studied. NIH3T3 cells were transfected with the recombinant
      pXJ41-hlc14 plasmid, and the expression of hlc-14 cDNA was detected and
      characterized immunohistochemically. Soft agar colony formation assay of the
      transfectants was performed. RESULTS: A human lung cancer lambda gt 11 cDNA
      library of 1.4 x 10(6) pfu/ml was constructed. Six cDNA clones were isolated
      following 4 rounds of immunoscreening. The largest cDNA clone hlc-14 contained
      954 bp with no homology to any known gene when screened through GenBank. In the
      NIH3T3 cells transfectant of hlc-14 cDNA, the expression of the lung cancer
      associated antigen was demonstrated. The ability of colony formation of the
      transfectant in the soft agar was enhanced. CONCLUSION: The hlc-14 clone is a
      novel human lung cancer-associated antigen cDNA. It provides clues for the study
      of carcinogenesis mechanism of lung cancer and a novel target gene for the gene
      therapy of lung cancer.

PMID- 10920962
TI  - [Immunoradiometric assay of tumor marker CA15-3 and its clinical application].
AB  - OBJECTIVE: To develop a new tumor marker immunoradiometric assay and to evaluate
      its preliminary clinical application. METHODS: With monoclonal antibodies Ma552
      and Ma695 from Sweden, a sandwich immunoradiometric assay was developed with
      Ma552 as catching antibody and Ma695 as tracer. The Ma552 was coated on
      polystyrene beads, and Ma695 was labeled with 125-I. The reaction was one step at
      room temperature. RESULTS: Bmax/B0 of the standard curve was 82. The sensitivity
      of this assay was 0.3 u/ml, CV within assay and CV between assays were 8% and
      10%, respectively. Serum level of CA 15-3 in 50 normal women was 11.3 +/- 3.9
      u/ml with a false positive rate of 0% based on the cut-off value of 30 U/ml. In
      40 patients with benign breast diseases the serum level was 9.6 +/- 5.8 u/ml with
      a false positive rate of 0%. In 65 cases of breast cancers in different stages it
      was 88.4 +/- 159.6 u/ml before treatments with a total positive detection rate of
      50.8%. Metastases, especially, bone metastases caused significant serum CA15-3
      elevation, with 100% positive rate(n = 9). The positive rate of recurrences of
      beast cancers was 80% (n = 5). CONCLUSION: The newly established
      immunoradiometric assay of CA15-3 is highly useful in the diagnosis, differential
      diagnosis, and monitoring of metastases and recurrences of breast cancer, and is
      superior to CEA.

PMID- 10920963
TI  - [Effect of cyclin D1 protein expression on the prognosis of esophageal squamous
      cell carcinoma treated with preoperative radiotherapy].
AB  - OBJECTIVE: To study the effect of cyclin D1 protein expression on the prognosis
      of esophageal carcinoma treated with preoperative radiotherapy. METHODS: From
      Nov. 1979 to Dec. 1996, 164 patients were treated with preoperative radiation
      followed by radical esophagectomy in our hospital. All cases were confirmed by
      pathology as squamous-cell carcinoma. Two vertical radiation fields were used to
      deliver a total tumor dose of 30-40 Gy, with 15-20 fractions in 3-4 weeks.
      Immunohistochemical staining of cyclin D1 was performed using a streptavidin
      biotin staining technique. RESULTS: Cyclin D1 protein expression was positive in
      62.5%(65/104) and 60.8%(93/153) for pre- and post-radiation tumor specimens,
      respectively. The expression level did not change following radiation. Post
      radiation cyclin D1 expression influenced the survival (P = 0.055), and the
      survival rate differed significantly between patients who expressed cyclin D1 and
      those who did not (P = 0.02). CONCLUSION: Cyclin D1 expression is of prognostic
      value for esophageal carcinoma. It may provide a reference criterion for the
      clinical staging of esophageal cancer.

PMID- 10920964
TI  - [Imaging manifestations of tumors metastasized in fatty liver].
AB  - OBJECTIVE: To evaluate the manifestations of tumors metastasized in fatty liver
      and the value of various imaging modalities, especially CT. METHODS: Nine cases
      of tumors metastasized in fatty liver were proved by clinical follow-up for 3-13
      months. The primary neoplasms were breast carcinoma in 6 cases; ovarian
      carcinoma, malignant melanoma and colon carcinoma, one case for each. All had
      CT(19 episodes) and ultrasonography (US, 20 episodes). Four cases had MRI and 2
      cases had DSA. RESULTS: Liver metastatic lesions were missed by US in 2 cases
      with moderate to marked fatty liver. On CT without contrast administrations,
      fatty liver was divided into marked, moderate and mild degree according to the
      density of hepatic parenchyma which was lower than that of the spleen; lower and
      higher than or equal to that of the intrahepatic blood vessels. Depending on the
      degree of fat infiltration(FI), the density of the metastatic lesions was high
      when FI was marked and low when FI was mild. However, when FI was moderate, the
      density of the metastatic lesions varied, being high, equal or low. On enhanced
      CT, all of the lesions were enhanced with moderate to marked fatty liver
      background. Lesions were heterogeneous in 4 cases. On plain CT, metastatic
      lesions had high-density rim, 2-6 mm in width in 4 cases. In SE sequence of MRI,
      metastatic lesions were hypointense on T1W and hyperintense on T2W, and
      moderately hyperintense on opposed-phase. CONCLUSION: Tumors metastasized in
      fatty liver show a broad spectrum of image manifestations. They are related to
      the degree of fat infiltration. On plain CT, isodense lesions are easily escaped
      detection when moderate degree of fatty liver is present. Contrast
      administrations is mandatory. Liver metastases is suggested if a lesion is found
      with hyperattenuating rim on plain CT, or appears heterogeneous after
      enhancement. MRI is of diagnostic help.

PMID- 10920965
TI  - [CT findings of calcified liver metastases].
AB  - OBJECTIVE: To observe the CT findings of 13 cases with calcified liver
      metastases. METHODS: The primary tumors were 10 cases of colonic carcinoma and 3
      cases of rectal carcinoma. CT and ultrasonic examinations of these 13 cases
      revealed calcified liver metastases. One case had laparotomy and biopsy,
      pathological diagnosis was liver metastases with necrosis and focal
      calcifications. RESULTS: There were 3 types of CT findings of calcified liver
      metastases: (1) sand-like calcifications conglomerate into a mass or circular
      clump, (2) irregular patchy calcifications, (3) small punctate calcifications.
      These calcifications were either in the center or the periphery of a single or
      multiple low density masses. CONCLUSION: Calcified liver metastases are uncommon.
      The primary tumor is usually colon carcinoma. Calcification can also be seen in
      carcinomas of the ovary, stomach and breast metastasized to the liver and primary
      carcinoma of the liver. When calcified liver metastasis is revealed by CT in
      patient with unknown primary tumor, colon cancer may be suggested.

PMID- 10920967
TI  - [Surgical treatment results for carcinoma of the gastric cardia in 1832 cases].
AB  - OBJECTIVE: To evaluate the results of surgical treatment for carcinoma of the
      gastric cardia and the prognostic factors. METHODS: The prognostic factors were
      assessed with 5-year survival rates which was estimated using life table method
      in 1832 cases. The difference between groups was assessed by the log rank test.
      RESULTS: The overall resection rate was 76.3% and the radical resection rate
      53.4%. The overall 5-year survival rate was 23.5% while in patients treated with
      curative resection it was 29.9%. The 5-year survival rate was 29.4% in patients
      received preoperative radiation and 21.5% in patients treated with surgery alone
      (P > 0.05). Patients whose upper margin of resection was longer than 5 cm away
      from the tumor had higher 5-year survival rate (25.8%) than those with margin of
      resection less than 5 cm (18.4%). The difference was statistically significant (P
      < 0.05). CONCLUSION: Preoperative radiation can increase the survival rate, but
      it was not statistically significant. Increasing the margin of resection to > 5
      cm can improve survival.

PMID- 10920966
TI  - [Imaging findings of primary sarcoma in the kidney].
AB  - OBJECTIVE: To reveal the characteristic findings of primary sarcoma of the
      kidney. METHODS: From December 1988 through February 1996, seven cases of renal
      sarcoma confirmed by histo-pathology were retrospectively reviewed, including 3
      leiomyosarcoma and 1 for each of liposarcoma, fibrosarcoma, malignant fibrous
      histiocytoma and malignant Schwannoma. Image material: CT in 6 cases,
      ultrasonography in 6 cases and MRI in 1 case. RESULTS: The tumor was located in
      renal parenchyma in 6 cases and in renal pelvis in 1 case. On the images, it was
      commonly a large mass with irregular margin, indefinite, circumscribed and
      heterogeneous in density with necrosis inside as observed on the CT scan and 2
      cases with median to hyperattenuation on the enhanced CT scan; 4/6 cases gave
      median heterogeneous mixed echo and 2/6 cases appeared as even hypoechoic mass on
      the ultrasonogram. On MRI, the mass gave isosignal intensity on T1WI and
      increased signal intensity with moderate heterogeneity was seen on T2WI or became
      more enhanced and heterogeneous but no more than renal parenchyma on the enhanced
      T1WI of MRI. Big tumor thrombus in the inferior vena cava and renal vein was
      noted in the fibrosarcoma. CONCLUSIONS: Primary renal sarcomas give imaging
      findings characteristic of malignant tumor but without histological specificity
      and can not be differentiated from renal cell carcinoma. The enhanced CT and MRI
      capable of providing useful information of the localization, changes in
      density/signal and extent of invasion of the tumor, are beneficial to the
      differential diagnosis and managements.

PMID- 10920968
TI  - [Application of pectoralis major myocutaneous flap in the reconstruction of
      tongue: an analysis of 86 cases].
AB  - OBJECTIVE: To analyze the results of the use of pectoralis major myocutaneous
      (PMM) flap in the reconstruction of tongue. METHODS: From 1984 to 1995, PMM flap
      was applied in 86 cases with cancer of tongue after radical resection for the
      immediate reconstruction of the lingual defect. RESULTS: Notwithstanding the
      advanced lesions in stages T3 and T4, patients had good survival and functional
      results. The 1-, 3- and 5-year survival rate was 86.0%, 51.2% and 23.3%,
      respectively. There was complete flap necrosis in one case and partial necrosis
      in fifteen cases, but the latter spontaneously regressed. The swallowing and
      speech rehabilitations following surgical treatment for tongue cancer were
      acceptable, considering the advanced disease status. CONCLUSION: The PMM flap
      with its abundant tissue and excellent blood supply and anatomic proximity
      provides a reliable method of primary reconstruction of the substance of the
      tongue. The surgical procedure is simple, easy to perform. Reconstruction of the
      tongue with PMM flap meets the clinical requirements in the shape, communication
      and swallowing rehabilitations. The PMM flap is a reliable material for the
      reconstruction of tongue with major defect following subtotal glossectomy.

PMID- 10920970
TI  - [A phase II clinical study of China-made paclitaxel in the treatment of cancer
      patients].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of China-made paclitaxel in
      patients with a variety of advanced malignancies. METHODS: Paclitaxel was
      administered by i.v. infusion at a dose of 175 mg/m2 in 3-hour every three weeks.
      All patients received premedication(dexamethasone, diphenhydramine and
      cimetidine) to prevent allergic reactions. RESULTS: Of 116 patients, 114 patients
      received 2 to 3 courses of therapy and were evaluable for response. The overall
      response rate for ovarian cancer was 46.7%, for breast cancer 56.4%, for non
      small-cell lung cancer 25.0%, for small-cell lung cancer 66.7%, and for
      nasopharyngeal cancer 41.7%. Responses were also achieved in patients who had
      failed to respond to prior chemotherapy, with the overall response rate of 42.9%
      for ovarian cancer, 57.6% for breast cancer, 33.3% for non-small-cell lung
      cancer, 25.0% for small-cell lung cancer, and 40.0% for nasopharyngeal cancer.
      Paclitaxel did not show cross-resistance with doxorubicin and cisplatin. The
      major toxicity associated with paclitaxel included neutropenia, arthralgia,
      myalgia, numbness of hands and feet and alopecia. No severe hypersensitivity
      reactions were observed. CONCLUSION: At the above-mentioned dose and schedule,
      paclitaxel is effective with tolerable side effects.

PMID- 10920971
TI  - [A randomized trial of Zudan in the prophylaxis of nausea and vomiting induced by
      cisplatin].
AB  - OBJECTIVE: To study the anti-emetic effect of Zudan on high-dose cisplatin and
      its toxicity. METHODS: A randomized, crossover assay was used in thirty patients
      who received cisplatin chemotherapy to compare the efficacy and the toxicity of
      identical dose of Zudan and Zofran. RESULTS: The response rate of acute vomiting
      induced by cisplatin was 70.0% in patients receiving Zudan and 63.3% in those
      receiving Zofran. Complete response rate was 56.7% in Zudan arm and 53.3% in
      Zofran arm. The two arms were not remarkably different in response rates or
      adverse reactions. CONCLUSION: Zudan is safe and effective in the control of
      vomiting induced by cisplatin.

PMID- 10920969
TI  - [Short-and long-term therapeutic effects of brachytherapy on intracavitary
      residual tumor in 563 nasopharyngeal carcinoma (NPC) patients].
AB  - OBJECTIVE: To evaluates the effect of brachytherapy on intracavitary residual
      tumor in patients with NPC after external radiation therapy. METHODS: Five
      hundred fifty three NPC patients with residual tumor in the nasopharynx were
      treated with large dose brachytherapy (20-25 Gy). The treatment results were
      retrospectively evaluated. RESULTS: Within 3 months after brachytherapy, the
      overall regression rate of the residual tumor was 90.4%. Upon long-term follow
      up, the 1-, 3-, and 5-year survival rate was 89.6%, 67.0% and 55.4%,
      respectively. The major complications of the after-loading treatment were nasal
      obstruction (16.2%), necrosis of the naso-pharynx (0.9%) and perforation of soft
      palate in 2 patients. CONCLUSION: Brachytherapy is effective in the treatment of
      residual NPC especially in patients in early stage. It may not be helpful for
      stage IV patients.

PMID- 10920972
TI  - [Treatment of malignant germ cell tumors of the ovary: a clinical analysis of 233
      cases].
AB  - OBJECTIVE: To evaluate the treatment methods of malignant germ cell tumors of the
      ovary. METHODS: Two hundred thirty three patients with malignant germ cell tumors
      of the ovary treated during 1958 through 1993 were retrospectively analyzed. The
      number of patients in different stage of the disease was as follows: stage I, 94;
      stage II-IV, 43; recurrence or metastasis, 96. Unilateral salpingo-oophorectomy
      was performed in 78 patients, or total abdominal hysterectomy and bilateral
      salpingo-oophorectomy with or without omentectomy and appendectomy was performed
      in 151 cases, and biopsy in 4 cases. Operation alone was done in 17 cases,
      operation plus radiotherapy with or without chemotherapy in 65, operation plus
      chemotherapy in 151 cases. RESULTS: Of the 233 patients 127 were disease-free.
      The number of survivors in stage I patients was 78, in stage II-IV was 17. There
      were 32 cases with recurrence and metastasis. The overall 5-year survival rate
      was 55.6%. The 5-year survival rate differed between dysgerminoma and
      nondysgerminomatous tumurs being 84.2% for the former and 44.6% for the latter.
      In patients with nondysgerminomatous tumors, chemotherapy with PVB and BEP
      regimens gave a 5-year survival rate of 66.0% and 73.3%, respectively.
      CONCLUSION: Malignant germ cell tumors of the ovary is very sensitive to
      chemotherapy. The PVB and BEP regimens result in excellent response in these
      patients. Complete remission and preservation of fertility can be obtained in
      patients with early tumors. Preoperative chemotherapy and postoperative adjuvant
      chemotherapy can improve survival in patients with advanced tumors.

PMID- 10920974
TI  - [Allelic loss on chromosome 3p21-26 in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To determine the frequency and extent of loss of heterozygosity (LOH)
      on chromosome 3p in nasopharyngeal carcinoma (NPC). METHODS: Sixteen loci on
      chromosome bands 3p21-26 in 24 tumors was studied by using microsatellite
      analysis. RESULTS: LOH on 3p21-26 was found in 16 of 24 tumors (66.7%). The
      highest frequency of the allelic loss was found in two adjacent loci D3S1620(50%,
      11/22) and D3S1560 (50%, 9/18). Eight cases showed LOH in one contiguous region
      and 5 cases in more than one region. Sample 1, 3, 4, 7, 8, 10, 16, 17, 18, 19,
      and 22 had a contiguous stretch of allelic loss between D3S1297 and D3S1597.
      CONCLUSION: The smallest common LOH/deletion region seems likely to lie between
      D3S1620(3p26.2-26.3) and D3S1560(3p25.3). The allelic loss map defined here will
      facilitate finer mapping of putative tumor suppressor gene loci and positional
      cloning of such genes, which may play a role in carcinogenesis of NPC.

PMID- 10920973
TI  - [The effect of Epstein-Barr virus gene BHRF1 expression on the apoptotic
      resistance of nasopharyngeal carcinoma cells].
AB  - OBJECTIVE: To investigate the effect of EB virus gene BHRF1 expression on the
      apoptotic resistance of nasopharyngeal carcinoma cell. METHODS: Expression vector
      for BHRF1 was constructed and transfected into nsaopharyngeal carcinoma cell
      line, CNE2. The alteration of biologic behaviour of the transfected cells was
      tested after 60Co radiation. RESULTS: BHRF1 expression could inhibit the
      expression of proliferative cell nuclear antigen, redistribute cell cycle,
      decrease cell sensitivity to radiation, and enhance their survival ability.
      CONCLUSION: It is suggested that BHRF1 expression can increase the apoptotic
      resistance induced by radiation.

PMID- 10920975
TI  - [The examination of EBV-DNase gene fragment in the paraffin embedded NPC, pre
      cancerous and high risk population nasopharyngeal tissues].
AB  - OBJECTIVE: To examine if EB virus enters nasopharyngeal epithelial cells in the
      course of the tumorigenesis in nasopharyngeal carcinoma (NPC). METHODS: Based on
      the annual investigation of Si-Hui county, a cancer-prevention base of the Sun
      Yet-sen University of Medical Sciences and Tumour Hospital outpatient clinic,
      more than 450 paraffin-embedded tissues with NPC, and with pre-cancerous lesions
      in high risk populations were collected for the detection of EBV-DNase gene
      fragment by an optimized PCR method. RESULTS: In 145 of the 149(97.3%) cases with
      invasive NPC, and 2 of 4 cases with in situ NPC, EBV-DNase gene was detected.
      However, in Sihui, Canton, a high-risk county for NPC, only 2 of the 155 subjects
      with nasopharyngeal precancerous state was the gene positive, and none of the 47
      cases examined in the out-patient department of the Tumor Hospital with
      precancerous lesions in the nasopharynx was positive. CONCLUSION: EBV is seldomly
      detected in the non-malignant and precancerous lesions in the nasopharynx in high
      risk populations. It implies that EBV is probably not etiologically involved in
      the genesis of NPC.

PMID- 10920976
TI  - [Cloning and identification of cDNA fragments related to human esophageal
      cancer].
AB  - OBJECTIVE: To search new genes related to human esophageal cancer (EC) for
      revealing carcinogenesis mechanism and genetic susceptibility of EC. METHODS:
      Three normal esophageal epithelia (including 1 tumor-adjacent tissue) and two
      primary squamous cell carcinomas collected from high incidence family in Lin-xian
      county were studied using technique of mRNA differential display. The
      differential fragments were sequenced and identified by RT-PCR assay. RESULTS:
      (1) Eighteen differential fragments were isolated and identified, 13 of which
      were expressed in normal esophageal epithelia but not in EC(assigned as normal
      esophageal gene, NEG), while 5 were expressed in EC but not in normal esophageal
      epithelia(assigned as mutated esophageal gene, MEG). (2) Four NEG fragments were
      not homologous to the known sequences in the public database of GenBank (of NLM
      in USA). These 4 fragments were assigned as esophageal cancer related gene (ECRG)
      1 to 4. (3)The remaining 14 fragments were homologues to 12 known genes or gene
      fragment. Their role in EC remains unclear. (4) Using RT-PCR technique, the
      expression of ECRG between normal epithelia and EC was significantly different.
      (5) All 4 ECRG genes were expressed in cDNA libraries derived from normal fetal
      brain, adult brain, liver, kidney, testis, bone marrow and skeletal muscle. (6)
      In the 20 cancerous and tumor-adjacent tissues obtained from the liver, lung,
      breast, colo-rectum and endometria, ECRG1 and ECRG2 was not detected by RT-PCR,
      while ECRG3 was highly expressed. For the ECRG4 the expression was much stronger
      in tumor-adjacent tissues than in cancerous tissues. CONCLUSION: ECRG 1 and ECRG2
      may contribute to the causation and progression of the EC in Lin-xian, and may be
      candidates of tumor suppressor genes.

PMID- 10920977
TI  - [Association of fragile histidine triad gene (FHIT) with susceptibility to
      esophageal cancer. A preliminary study].
AB  - OBJECTIVE: To identify loss of heterozygosity(LOH) and homozygous deletion on
      loci of fragile histidine triad gene(FHIT). METHODS: Gene regions have been
      detected in 73 pairs of esophageal cancer samples using microsatellite DNA
      markers. Deletions of FHIT cDNA on 14 fresh esophageal cancer(EC) samples and 2
      EC cell lines were screened by RT-PCR and DNA sequencing. RESULTS: High frequency
      of LOH was detected on loci D3S1480, D3S1481, D3S1234. Of 14 esophageal cancer
      samples 9(64.3%) had deletions of the FHIT gene, 7 of them were deletions in exon
      1-4, and 5 of them were deletions in exon 5-9, the coding region. The whole FHIT
      gene was found deleted in an EC cell line, EC8733. CONCLUSION: It is suggested
      that the FHIT gene may play an important role in the genesis of EC. However,
      further study is needed to ascertain whether FHIT gene is indeed an EC
      susceptibility gene.

PMID- 10920978
TI  - [Telomerase activity in human gastric and colorectal cancer].
AB  - OBJECTIVE: To study telomerase activity in patients with gastric and colorectal
      cancer. METHODS: Telomerase activity in tumor samples, including 9 colonic, 20
      rectal and 11 gastric carcinomas, was examined by telomeric repeat amplification
      protocol(TRAP) assay. Thirty-nine samples from tumor-adjacent tissues were also
      assayed. RESULTS: Ninety per cent(36 out of 40 tumor samples) exhibited
      telomerase activity regardless of tumor stage or differentiation. However,
      telomerase activity in the tumor-adjacent tissues could be detected only in 1 of
      39 specimens. CONCLUSION: Telomerase may be a good diagnostic biomarker for tumor
      detection.

PMID- 10920981
TI  - [Enhanced antitumor effect of suicide gene therapy by SCF, GM-CSF gene transfer
      in vivo and its immunological mechanism].
AB  - OBJECTIVE: To explore an efficient approach to enhance antitumor effect of
      suicide gene therapy by improving in vivo antigen presenting function and their
      immunological mechanisms. METHODS: The CT26 colon adenocarcinoma was treated with
      CD/5FC system combined with the mGM-CSF or/and mSCF gene transfection, and the
      antitumor effects were evaluated by the tumor growth, tumor-free mouse rate,
      splenic CTL activity and cytokine expression of tumor milieu. RESULTS: The tumor
      burden was reduced significantly and higher survival rate was obtained after the
      combined treatment. It was found that some cytokines(including mIL-4, mIL-2, mIFN
      gamma and mTNF-alpha) were expressed in the tumor milieu after mGM-CSF or/and
      mSCF gene transfection following CD/5FC treatment but not in the control groups.
      The cytotoxic activity against CT26 cells of spleen cells of the treated mice was
      significantly incressed. CONCLUSION: The combination of mSCF or/and mGM-CSF gene
      transfection enhances the antitumor effect of the suicide gene therapy. Such an
      enhancement is associated with the induction of specific antitumor immune
      response and secretion of cytokines in tumor milieu.

PMID- 10920980
TI  - [A study on the correlation between the activity of 72,000 type IV collagenase
      and the metastatic potential of cancer cells].
AB  - OBJECTIVE: To evaluate the enzyme activity of 72,000 type IV collagenase and its
      relationship with the metastatic potential of cancer cells. METHODS: The levels
      of secreted 72,000 type IV collagenase in the conditioned media of five human
      cancer cell lines with different metastatic potential and a normal lung
      fibroblast strain treated with cancer cell culture media were examined by gelatin
      zymography and densitometric analysis. RESULTS: The levels of 72,000 type IV
      collagenase secreted by cancer cells with high metastatic potential (PG, WM451
      and WM983a) were higher than those secreted by cancer cells with low metastatic
      potential (PAa and WM35). In the conditioned media of fibroblasts which were
      treated with the culture media of PG and WM451, enhanced levels of activation
      were observed. CONCLUSION: The secretion of 72,000 type IV collagenase is closely
      correlated to the metastatic potential of cancer cells. The cancer cells with
      high metastatic potential may possibly through certain soluble mediators
      stimulate normal fibroblasts to activate 72,000 type IV procollagenase.

PMID- 10920979
TI  - [Detection of human telomerase activity by telomerase TRAP-ELISA assay].
AB  - OBJECTIVE: Telomeric repeat amplification protocol (TRAP) is now a conventional
      assay for detecting telomerase activity. However, this method presents problems
      owing to tedious quantification, radioisotopic handling and limited number of
      samples that can be examined each time. In order to alleviate these
      inconveniences, a novel telomerase TRAP-ELISA assay for human telomerase activity
      was developed. METHODS: Telomerase TRAP-ELISA assay is a system based on the
      combination of PCR-ELISA with TRAP. It was used to detect telomerase activity in
      293 cells and RNase-pretreated or heat-treated cells as control. RESULTS:
      Telomerase activity assayed by TRAP-ELISA was positive when the number of 293
      cells examined was 10, 10(2), 10(3), and 10(4). The A(formerly called OD) value
      depended on the number of 293 cells used in the assay. Telomerase activity of
      RNase-pretreated or heat-treated cells, and human normal endothelial cell was
      negative. The result of telomerase TRAP-ELISA was available within one day and
      was handled without radioisotope. CONCLUSION: Telomerase TRAP-ELISA assay is a
      non-radioisotopic, fast and quantitative method for detecting human telomerase
      activity.

PMID- 10920982
TI  - [Cloning and expression of a gene associated with HL60 cell apoptosis induced by
      inhibition of polyamine biosynthesis].
AB  - OBJECTIVE: To clone the gene associated with apoptosis induced by an inhibitor of
      polyamine biosynthesis, alpha-difluoromethylomithine (DFMO). METHODS: The
      differential substraction screening was used for gene cloning. The gene
      expression and apoptosis of transfected HL60 cells were detected by Northern
      blot, morphological assay, FCM and ladder map of DNA electrophoresis,
      respectively. RESULTS: An apoptosis-associated gene named dF4 was cloned from
      HL60 cells treated with polyamine biosynthesis inhibitor. The programmed cell
      death was demonstrated in the HL60 cells transfected by dF4 gene. CONCLUSION: dF4
      gene cloned in this study could be a gene regulating apoptosis of HL60 cells.

PMID- 10920983
TI  - [Comparative study of expression levels of the major human heat shock proteins in
      cancer and normal tissues].
AB  - OBJECTIVE: To investigate and compare mRNA expression levels of the major human
      HSPs (including HSP90 alpha, HSP90 beta, HSP70, HSC70 and HSP27) in 25 cases of
      laryngeal carcinomas and normal controls. METHODS: mRNA slot blot hybridization
      technique was used and cDNA probes of HSP27, HSC70 and HSP90 beta were prepared
      with PCR method. RESULTS: HSP90 alpha and HSP70 expression was significantly
      enhanced approximately 5 fold in laryngeal cancer tissues compared to that in the
      normal larynx tissues while HSP27, HSC70 and HSP90 beta expression was at similar
      levels. CONCLUSION: The results suggest that HSP90 alpha and HSP70 may play more
      important role in the carcinogenic process of laryngeal cancer. To find out
      mechanisms involved will pave the way for the application of HSPs on the biologic
      therapy of laryngeal cancer.

PMID- 10920984
TI  - [Experimental study of the therapeutic effects of an anti-endothelial cell
      monoclonal antibody BVE-1 for solid tumor xenograft in nude mice].
AB  - OBJECTIVE: To study the possibility of targeting endothelial cells with
      monoclonal antibody for the therapy of solid tumors. METHODS: Leiomyosarcoma cell
      line SK-LMS-1, liver cancer cell line 7721 and pancreatic cancer cell line SW1990
      xenografts in nude mice were treated i.p. with an anti-endothelial cell
      monoclonal antibody BVE-1 or 131I labeled BVE-1, with normal mouse IgG or 131I
      labeled IgG as controls. The tumor volume was measured at regular intervals
      following treatment. After sacrifice of the mice, the tumor was histologically
      examined and the intra-tumoral microvessel density(TMVD) recorded. RESULTS: The
      tumor growth inhibition effects in mice treated with BVE-1 was 49.8% in SK-LMS-1,
      48.7% in SW1990 and 70.5% in 7721, respectively. Metastasis of leiomyosarcoma was
      also inhibited by the antibody treatment, leading to decreased death rate. This
      effect was enhanced when treated with 131I-labeled BVE-1 with an increase of
      tumor growth inhibition rate to 82.2%-86.6%. Pathologically, capillary
      endothelial cells degeneration, occlusion of capillaries and massive tumor cells
      necrosis around the degenerated vessels were observed in the BVE-1 treated mice.
      TMVD was significantly lower in the BVE-1 treated mice than that in mice treated
      with normal mouse IgG and in the untreated mice. CONCLUSION: The monoclonal
      antibody against vascular endothelial cells BVE-1 is effective in the treatment
      of human cancer xeno-transplanted in nude mice through the induction of capillary
      endothelial degeneration and vascular occlusion inside of the tumor. It can be
      used as a novel strategic approach in the treatment of human solid tumors.

PMID- 10920985
TI  - [Mutations of APC gene MCR region in sporadic colorectal adenomas and
      carcinomas].
AB  - OBJECTIVE: Fifteen specimens of colorectal adenomas and 45 specimens of
      carcinomas and each of their normal mucosa were analyzed for the APC gene exon 15
      MCR(mutation cluster region). METHODS: Gene mutation was examined by PCR-SSCP
      technique. RESULTS: In three out of 15 cases of adenomas(20.0%) and 10 out of 45
      cases of carcinomas(22.2%), mutations at MCR was detected. In colorectal
      carcinoma, APC gene mutation was not related to size, location, histologic
      features and lymph node metastases. In MCR region, 1260-1359 codons gave a lowest
      mutation frequency, while 1339-1436 codons showed the highest mutation frequency.
      CONCLUSION: APC gene mutation detected in colorecral adenomas indicates that the
      APC gene mutation is an early event in colorectal carcinogenesis. It helps early
      diagnosis of colorectal carcinoma.

PMID- 10920986
TI  - [The effect of recombinant tissue inhibitor of metalloproteinase-3 (TIMP-3) on
      tumor growth and metastases].
AB  - OBJECTIVE: To investigate the anti-cancer effect of tissue inhibitor of
      metalloproteinase-3 (TIMP-3) and its mechanism of action. METHODS: Recombinant
      TIMP-3(rTIMP-3) was prepared and used to study its effect on tumor growth and
      metastases in mice, and its effect on angiogenesis in chicken embryo allantoic
      membrane (CAM). RESULTS: rTIMP-3 was able to inhibit growth of subcutaneously
      implanted S180 sarcoma and hepatic carcinoma H22 in a dose-dependent manner. When
      the rTIMP-3 was given i.p. at a daily dose of 20 mg/kg body weight for 10 days,
      the growth of S180 sarcoma and H22 carcinoma was inhibited by 63.2% and 73.4%,
      respectively. The metastases of i.v. injected Lewis lung carcinoma(3LLC) was also
      suppressed by rTIMP-3, with an inhibition rate of 59.8%. rTIMP-3 was found to
      significantly inhibit angiogenesis in CAM assay. CONCLUSION: rTIMP-3 has anti
      cancer activity, and the mechanism of action might be associated with its
      inhibition on extracellular matrix degradation and anti-angiogenesis.

PMID- 10920987
TI  - [Bcl-2/JH gene re-arrangement determined by PCR as a means to detect minimal
      residual disease in malignant lymphomas].
AB  - OBJECTIVE: To develop a sensitive method to detect minimal residual disease and
      to elucidate the significance of bcl-2 gene rearrangement in diagnosis and
      therapy of malignant lymphoma. METHODS: Using polymerase chain reaction(PCR) to
      detect bcl-2 gene rearrangement and using serial dilution method to define the
      sensitivity of PCR. RESULTS: In 9 different malignant lymphoma cell lines, Su-DHL
      4 and Su-DHL-6 were shown bcl-2(MBR)/JH rearrangement, the sensitivity of PCR was
      1:10(5). In 16 patients with follicular lymphoma, the peripheral blood and bone
      marrow were PCR positive in 4 both at initial diagnosis and after complete
      remission. CONCLUSION: Detection of bcl-2 gene rearrangement by PCR provides a
      sensitive and specific assay of minimal residual disease. It helps improve
      staging of disease, stratification and evaluation of treatment.

PMID- 10920988
TI  - [Recurrence pattern and prognosis of esophageal cancer following tumor
      resection].
AB  - OBJECTIVE: To determine the recurrence patterns and prognosis after resection of
      esophageal cancer. METHODS: One hundred eighty five patients who developed
      recurrence after curative resection for squamous-cell carcinoma of the thoracic
      esophagus were analyzed retrospectively. RESULTS: The median recurrence time was
      303 days. Recurrence pattern was catagorized into lymphatic, hematogenous, mixed
      and anastomotic. The number of patients in each recurrence group was 137, 11, 29,
      and 8, respectively. The 0.5-, 1-, 2-, 3-, and 4-year overall survival rate was
      70.7%, 47.1%, 19.8%, 12.2% and 0%, respectively. Multivariate analysis showed
      that depth of tumor invasion, lymph node metastasis, operative procedure and
      different regimens of therapy were significant prognostic factors. CONCLUSION:
      Lymph node metastasis and the depth of invasion may reflect the biologic behavior
      of the tumor. Esophagectomy with cervical anastomasis is recommended, additional
      cervical lymphadenectomy is beneficial in a few patients. Radiotherapy combined
      with chemotherapy may prolong survival time of patients with recurrence.

PMID- 10920990
TI  - [Histopathological study of local invasiveness of transglottic cancer].
AB  - OBJECTIVE: To explore the characteristics and relevant factors of transglottic
      cancer invading paraglottic space (PGS) and pre-epiglottic space (PES). METHODS:
      Whole-organ serial sections of 50 transglottic cancer specimens were studied
      histopathologically. RESULTS: Transglottic cancer invading PGS was observed in 39
      of the 50 (78.0%) specimens. In 32 of the 39 specimens, the invasion outstripped
      PGS, involving elastic cone in 26(81.3%), thyroid cartilage in 24(75.0%) and
      cricothyroid membrane in 20(62.5%). Transglottic cancer invading PES was seen in
      23 of the 50 specimens (46.0%). With the increase in tumor staging and tumor
      size, PGS and PES became increasingly invaded. There were two possible routes of
      invasion to PES: a) extending anteriorly and upward via PGS; b) extending upward
      via anterior commissure to destroy the stem of epiglottic cartilage. CONCLUSION:
      PGS is easily invaded by transglottic cancer. Partial laryngectomy is recommended
      in patients with T3, T4 transglottic cancer larger than 20 mm in diameter.

PMID- 10920989
TI  - [Supraglottic horizontal laryngectomy for supraglottic carcinoma].
AB  - OBJECTIVE: To evaluate the therapeutic results of supraglottic horizontal
      laryngectomy (SHL) for T1 and selected T2, T3 and T4 supraglottic carcinoma.
      METHODS: One hundred and seven patients undergone SHL during the period of 1979
      through 1991 were reviewed retrospectively. All patients were followed up for at
      least 5 years. RESULTS: The 5 year-survival rate of 6 cases in stage I, 24 cases
      in stage II, 53 cases in stage III, and 24 cases in stage IV was 100.0%, 83.3%,
      71.7% and 41.7%, respectively. Of the 102 patients, 92.2% were decannulated, and
      91.6% of all patients achieved satisfactory recovery of phonation. CONCLUSION:
      SHL is a reliable surgical approach for selected supraglottic carcinoma, even for
      some advanced lesions, provided the tumor has not extended below the ventricle.
      The upper neck dissection can be used as an exploratory measure. For N0 neck
      patients with supraglottic cancer, comprehensive neck dissection is not
      invariably performed to avoid overtreatment.

PMID- 10920993
TI  - [Arterial infusion chemotherapy for patients with advanced and moderately
      advanced cancer of urinary bladder].
AB  - OBJECTIVE: To study the effect of arterial infusion chemotherapy in patients with
      carcinoma of urinary bladder. METHODS: Eleven patients with advanced or
      moderately advanced cancer of the urinary bladder (10 transitional cell
      carcinoma, 1 squamous-cell carcinoma) who were for various reasons not suitable
      for surgical treatment were treated by arterial infusion chemotherapy according
      to Seldinger's percutaneous approach. RESULTS: The treatment results were
      satisfactory with an overall response rate of 90.9% (CR = 2, PR = 8). The average
      survival time of the 11 patients was 26.2 +/- 13.1 months. The 1-year survival
      rate was 81.8%. Side effects were mild. CONCLUSION: Arterial infusion
      chemotherapy is of use in patients with advanced or moderately advanced bladder
      cancer.

PMID- 10920992
TI  - [Interleukin-6 and its soluble receptors in human breast cancer].
AB  - OBJECTIVE: To study interleukin-6(IL-6) and its receptors in human breast cancer.
      METHODS: Using ELISA method and ABC immunohistochemistry, IL-6 and its receptors
      were examined in 45 cases of breast cancer, 10 cases of benign breast diseases
      and 17 cases of healthy women. RESULTS: High levels of serum IL-6 and its soluble
      receptors were frequently observed in breast cancer patients. The levels
      correlated with the stage and axillary lymph node involvement. The positive
      staining of IL-6, IL-6R alpha, gp130 were 68.9% in neoplasm tissue. CONCLUSION:
      IL-6 and its soluble receptors may be important paramenters reflecting the
      biological behaviour and prognosis of breast cancer.

PMID- 10920991
TI  - [Prognostic significance of P-glycoprotein expression in acute leukemia in
      adults].
AB  - OBJECTIVE: To explore the prognostic significance of P-glycoprotein (P-gp)
      expression in previously untreated acute leukemia in adults. METHODS: P-gp
      expression in 151 acute myeloblastic leukemia (AML) and 47 acute lymphoblastic
      leukemia (ALL) was determined by monoclonal antibody UIC2 and flow cytometry.
      RESULTS: The rate of complete remission (CR) differed between P-gp+ and P-gp- AML
      (20.5% vs 78.5%, P < 0.001), but the CR rate did not significantly differ between
      P-gp+ and P-gp- ALL(66.7% vs 80%, P > 0.05). The six-month relapse rate was
      significantly higher in P-gp+ group than that of P-gp- group (AML: 66.7% vs 8.7%,
      P < 0.001; ALL: 50% vs 9.5%, P < 0.05). The median disease-free survival time was
      shorter in P-gp+ group than in P-gp- group (AML: 5 months vs 13 months; ALL: 4
      months vs 13 months). CONCLUSION: Overexpression of P-gp is a poor prognostic
      factor in adult acute leukemia and P-gp detection is useful for the prediction of
      treatment response and early relapse.

PMID- 10920994
TI  - [Treatment of metastatic bone pain with Aredia(Pamidronate)].
AB  - OBJECTIVE: To evaluate the efficacy of Aredia to relieve pain due to metastatic
      bone tumor. METHODS: Aredia 60-90 mg in 500 ml 5% glucose or normal saline was
      given by i.v. infusion. The treatment was repeated at 2-4 week intervals.
      RESULTS: Complete relief of pain was observed in 9 patients, partial relief in 13
      patients. The treatment was of no effect in 3 patients. The therapeutic effect
      was achieved in 72.7% of the patients within 2 weeks. CONCLUSION: Aredia is a
      good pain reliever in patients with metastatic cancer of the bone.

PMID- 10920996
TI  - [The structure, function and mutation of Rb gene promoter in normal individuals
      and retinoblastoma patients].
AB  - OBJECTIVE: To investigate the DNA sequence of the 5' untranslated region of the
      Rb gene in normal individuals and retinoblastoma patients and identify the
      elements involved in transcription regulation of Rb gene. METHODS: SSCP analysis
      and direct genomic DNA sequencing were used to identify variations or alterations
      in DNA of normal adult WBC and tumor DNA of retinoblastoma patients. The
      different DNA fragments located in the 5' untranslated region of Rb gene were
      amplified and inserted into an expression plasmid with a CAT reporter gene. The
      capacity of transcription regulation of isolated DNA fragments was determined by
      CAT assay. RESULTS: A 240 bp DNA fragment located between -327(-)-87 bp upstream
      of the first starting codon was shown to be the sequence with essential promoter
      function. The Sp1/RBF-1, ATF and E2F binding sites were present in this region
      and positive and negative elements were found further upstream and downstream.
      Four of 5 naturally occurring mutations were identified in either Sp1/RBF-1 or
      ATF binding sites from 302 patients with retinoblastoma. All these mutants had
      reduced CAT activity. However, 100 cases of normal adults did not show any
      variant DNA sequence in the same region. CONCLUSION: The promoter DNA sequence of
      Rb gene is quite stable. Its variation usually leads to reduction in promoter
      activity which may be associated with genetic susceptibility to retinoblastoma.

PMID- 10920995
TI  - [The clinicopathological and immunophenotypical features of 162 cases of
      gastrointestinal stromal tumor].
AB  - OBJECTIVE: To demonstrate the clinicopathological and immunophenotypical features
      of gastrointestinal stromal tumor (GIST). METHODS: One hundred and sixty-two
      cases of GIST were retrospectively studied. Among them, forty-six cases were
      immunostained using antibodies against vimentin, CD34, muscle specific actin
      (MSA), smooth muscle actin (SMA), neuron specific enolase(NSE), S-100 protein,
      synaptophysin (SYN), cytokeratin(CK), CEA, LCA. RESULTS: Clinically, male
      patients predominated with a male to female ratio of 3.8:1. The average age was
      50 (range 6-74). The most common symptoms were gastrointestinal bleeding and
      abdominal mass in 45% and 39% of the cases, respectively. The common anatomical
      locations were stomach (43%), ileum (20%), jejunum (18%). Pathologically, all the
      tumor arose from the muscular layer. The tumor diameter varied from 0.5 to 43 cm.
      In 55% of the cases, the tumor was malignant. The main component cell types were
      spindle and epithelioid in appearance. Immunophenotypically, percentage of
      positivity for the 10 antibodies was as follows: vimentin, 100% (39/39), CD34,
      64% (23/36), MSA, 47% (16/34), SMA, 41% (14/34), NSE, 61% (17/28), S-100 protein,
      19% (4/21), SYN, 15% (3/20), CK, CEA, and LCA were negative. CONCLUSION: GIST is
      the most common mesenchymal tumor of the gastrointestinal tract. Immunostaining
      confirms that only some of the GIST shows partial differentiation toward smooth
      muscle, neuron, or both.

PMID- 10920997
TI  - [Inhibition effect of Swainsonine on the growth and metastasis of gastric cancer
      in vivo].
AB  - OBJECTIVE: To study the immunomodulating effect of Swainsonine (SW), an inhibitor
      of alpha-mannosidase II, and the inhibiting effect on the growth and metastasis
      of gastric cancer. METHODS: Nude mice with human gastric cancer xenograft
      orthotopically implanted into the gastric wall were fed with drinking water
      containing 3 mg/L SW for two days alternating with that containing no SW for two
      days until sacrificed eight weeks after tumor implantation. RESULTS: The mean
      tumor volume in the SW-treated group was significantly smaller than that of the
      control group (0.42 +/- 0.26 cm3 vs 1.60 +/- 0.36 cm3). Calculated by volume, the
      tumor growth was inhibited by 73.8%. Metastasis to the liver was observed in 20%
      and 80% of the SW-treated and control mice, while metastasis to the peritoneum
      was seen in 30% and 90% of SW-treated and control mice, respectively. The total
      number of splenic cells, and the NK cell activity both of PBL and splenic cells
      were all elevated. CONCLUSION: SW is effective in inhibiting tumor growth and
      metastasis of human gastric cancer in nude mice. Enhanced immune response, among
      other things, may be involved in the anti-tumor effect.

PMID- 10920998
TI  - [Antisense oligodeoxynucleotide of TGF alpha inhibits its gene expression and
      proliferation of a human glioma cell line].
AB  - OBJECTIVE: To study the effect of antisense oligodeoxynucleotide(ON) of TGF alpha
      on its gene expression in TJ 905 cell line. METHODS: Antisense and sense TGF
      alpha phosphorothioate ON (SON) and random SON were synthesized and transfected
      to TJ 905 cells mediated by lipofectin. Their effects on the TGF alpha gene
      expression were examined by in situ hybridization of TGF alpha mRNA,
      immunohistochemical study and cell count. RESULTS: (1) TGF alpha antisense SON
      could significantly inhibit the growth of TJ 905 cell line. The inhibition peaked
      at 24 hour after transfection, the inhibition rate reached 68% at 20 microM, and
      the effect decreased 72 hours after transfection. The inhibition effect was dose
      dependent. (2) Antisense TGF alpha SON inhibited TGF alpha expressions at both
      mRNA and protein levels. CONCLUSION: Antisense TGF alpha SON can inhibit the
      expressions of TGF alpha and markedly inhibit cell growth of human glioma TJ 905
      cell line. TGF alpha contributes in the growth potential of glioma.

PMID- 10920999
TI  - [Antitumor effect of M-CSF and/or IFN-gamma gene cotransfected-macrophages by
      intratumoral injection].
AB  - OBJECTIVE: To investigate the in vivo antitumor effects of M-CSF and/or IFN-gamma
      gene transfected-macrophages and their related immunological mechanisms. METHODS:
      Survival time and antitumor effects in vivo of tumor-bearing mice treated with
      gene-transfected macrophages were observed. NK cell and CTL activity was detected
      with 4 hr 51Cr release assay, cytotoxicity of macrophages was detected with
      indirect MTT methods, activity of IL-2, TNF, IFN-gamma were detected by routine
      methods. RESULTS: 25% of the tumor-bearing mice after treatment with IFN-gamma
      gene-transfected, M-CSF and IFN-gamma gene co-transfected macrophages survived
      more than 3 month. The CTL and macrophage activity of the tumor-bearing mice was
      enhanced. Levels of TNF, IL-2, IFN-gamma in the supernatants of splenocytes
      induced in vitro were also increased. Histologic analyses of the tumor tissue
      after treatment with M-CSF and/or IFN-gamma gene-transfected macrophages showed a
      large amount of lymphocyte infiltration. CONCLUSION: IFN-gamma and M-CSF gene co
      transfection into macrophages are proved to enhance their antitumor potential
      efficiently through direct augmentation of their tumoricidal cytotoxicity and
      induction of host antitumor immunity.

PMID- 10921000
TI  - [Efficient gene transfer mediated by retrovirus vector in leukemic cells].
AB  - OBJECTIVE: To establish an efficient and safe gene transfer system mediated by
      retrovirus for providing an experimental basis of gene therapy in human leukemia.
      METHODS: The retrovirus vector pLXSN, carrying the NeoR, was transferred into
      amphotropic packaging cell line GP + envAm12 by liposome method or by
      transduction. Retrovirus with higher titer was used to infect human leukemic cell
      lines NB4, U937 and THP-1. The efficiency of gene transduction was tesed on
      colonies formed by K562 cells after gene transduction. RESULTS: The titer of
      DOSPER liposome transfected GP + envAm12 pool on NIH3T3 cells was 8.0 x 10(5)
      CFU/ml while that of producer pool infected with mouse retrovirus was 1.6 x 10(7)
      CFU/ml. Integration of NeoR into human leukemic cells was confirmed by PCR. By
      both nested PCR and NeoR rescue assay, no helper virus was found. NeoR gene
      transfer with the efficiency as high as 93.3 to 100% in K562 cells was verified
      by semi-nested PCR on the colonies after seven days' culture. CONCLUSION: The
      efficiency and safety of the gene transfer system may provide an optimal
      experimental system in gene therapy for human leukemia.

PMID- 10921001
TI  - [WAF1/CIP1/p21 gene in wild type p53 and mutant p53 human breast cancer cell
      lines in relation to its cytobiological features].
AB  - OBJECTIVE: To study the WAF1/CIP1 gene DNA status, mRNA and protein expressions
      in human breast cancer cell line and its significance. METHODS: Using cell
      culture, molecular biological techniques such as Southern blot, Northern blot and
      immunocytochemical methods, the WAF1/CIP1 gene DNA status, mRNA and protein
      expression levels in MCF-7 expressing wild type p53(wtp53) and MDA-MB-231
      expressing mutant p53 (mtp53) human breast cancer cell lines were detected
      respectively. The p53 and mdm-2 protein expression levels and cytobiological
      features of the 2 cell lines were compared and correlated to their WAF1/CIP1 gene
      expression levels. RESULTS: (1) There was no difference in WAF1/CIP1 gene DNA
      status in the two breast cancer cell lines. Neither of them showed gene
      amplificatian or deletion. However, the WAF1/CIP1 mRNA and p21WAF1/CIP1 protein
      expression levels of MCF-7 cells were higer than those of MDA-MB-231 cells (P <
      0.05). (2) The character and cellular distribution of p53 protein in the two cell
      lines were clearly different. The expression level of mdm-2 proteion was
      significantly higher in MCE-7 than in MDA-MB-231 cells (P < 0.05). (3) Compered
      to the other breast cancer cell line, MCF-7 cells were better differentiated,
      grew more slowly and adhered more closely with each other. CONCLUSION: The
      WAF1/CIP1 gene expression at mRNA and protein levels is associated with p53
      phenotype and some cytobiological features of human breast cancer.

PMID- 10921002
TI  - [CYP2D6 and GSTM1 genetic polymorphism and lung cancer susceptibility].
AB  - OBJECTIVE: To evaluate the relationship between CYP2D6 and GSTM1 genetic
      polymorphism and lung cancer susceptibility among Cantonese in China. METHODS: In
      a case-control study, PCR was used to identify CYP2D6 and GSTM1 genotypes and
      restriction enzyme BstNI was used to identify a specific point mutation of
      CYP2D6. RESULTS: Between lung cancer patient group and normal control group
      CYP2D6 genetic polymorphism did not show frequency distribution differences but
      that of GSTM1 did (58.7% n = 46, 35.7%, n = 70, P < 0.05) OR = 2.56(1.11-2.44).
      CONCLUSION: There is no association between CYP2D6 G-A mutation and lung cancer
      susceptibility, while individuals with GSTM1 -/- genotype are susceptible to lung
      cancer.

PMID- 10921003
TI  - [PAH-DNA adduct in human lung cancer explants. A preliminary study].
AB  - OBJECTIVE: To study the influences of external exposure on polycyclic aromatic
      hydrocarbons (PAH)-DNA adduct formation in lung cancer patients. METHODS: On the
      basis of pilot experiments in mice, 32P post-labeling assay developed by
      Randerath was used to measure PAH-DNA adduct in human lung tissue explants.
      Relative adduct label(RAL) value was employed as a measure of adduct formation. A
      case-control study was designed using age-, sex-, and residence-matched patients
      with lung cancer and benign pulmonary diseases. RESULTS: Although the mean RAL
      value in male lung cancer patients was not significantly different from that in
      patients with benign diseases, patients who smoked cigarettes had significantly
      higher RAL value than those who did not smoke(27.62 x 10(-9) versus 11.42 x 10(
      9), P = 0.0015). In contrast, in female lung cancer patients, the RAL value was
      significantly higher in patients with lung cancer than in those with benign lung
      diseases (13.59 x 10(-9) versus 7.9 x 10(-9), P < 0.05). Moreover, significant
      difference in RAL values existed between female smokers and non-smokers. Cooking
      affected female patients only. Higher RAL values were seen in patients with
      squamous-cell carcinoma than with adenocarcinoma (P < 0.05). RAL values were
      significantly higher in poorly differentiated than in well-differentiated lung
      cancers (P < 0.05). A significant increase in RAL values was observed in patients
      with lymph node metastasis as compared with those without lymph node metastasis.
      CONCLUSION: PAH-DNA adduct level in lung tissue explants can be taken as a
      measure of environmental exposure and it correlates with the histological type,
      degree of differentiation and lymph node metastasis of lung cancer.

PMID- 10921004
TI  - [A study on apoptotic cell death during chemotherapy of patients with acute
      leukemia].
AB  - OBJECTIVE: To investigate whether apoptosis occurs in vivo in patients with acute
      leukemia during induction chemotherapy and its significance. METHODS: Apoptotic
      effect on peripheral blood of 20 patients with different types of acute leukemia
      prior to and during routine chemotherapy was studied by cell morphology, DNA
      electrophoresis and FCM-DNA analysis. RESULTS: After chemotherapy, with falls in
      WBC and blast count, no apoptotic cell appeared on smears of peripheral blood,
      nor did ladder pattern of DNA on electrophoresis and subdiploid peak on FCM.
      CONCLUSION: Although anticancer drugs have been shown to induce apoptosis in
      vitro, circulating apoptotic cells are hardly detected probably due to their
      rapid clearance from the circulation. It is more difficult to study apoptosis in
      vivo than in vitro.

PMID- 10921005
TI  - [Binding activity of retinoids with recombinant human retinoic acid receptor RAR
      alpha].
AB  - OBJECTIVE: To establish a model for the rapid screening of differentiation
      inducing agents. METHODS: Human RAR alpha cDNA was cloned into the PT7-7 plasmids
      and the human recombinant RAR alpha protein was expressed in Escherichia coli.
      The ligand-binding activity of the receptor with all-trans retinoic acid was
      studied by competitive binding assay. For comparison of the binding activity,
      five retinoids, with different activities and chemical structures, were chosen.
      The binding of these retinoids to RAR alpha was investigated and compared with
      the NBT reduction and acid phosphatase activity of HL-60 cells induced by these
      compounds. RESULTS: The binding activity of these retinoids was well correlated
      to their ability to induce differentiation of HL-60 cell line. CONCLUSION: This
      model could be used to screen differentiation-inducing agents.

PMID- 10921006
TI  - [Detection of type 6 human herpesvirus (HHV-6) specific DNA sequence in lymphoma
      tissues by PCR].
AB  - OBJECTIVE: To study the relationship between human herpesvirus-6 (HHV-6) and
      lymphoma in China. METHODS: The specimens of paraffin-embedded lymphoma tissue,
      leukemia cell lines and normal blood donor peripheral blood lymphocytes(PBL) were
      examined for the presence of HHV-6 DNA sequence by polymerase chain reaction
      (PCR). RESULTS: Of the 52 cases lymphoma studied, HHV-6 DNA sequence was detected
      in 21 cases; of 43 normal PBL, HHV-6 DNA sequence was detected in 8 cases. The
      difference was statistically significant (P < 0.05). HHV-6 DNA sequence was also
      present in two leukemia cell lines. CONCLUSION: The results suggest that HHV-6
      may be related to lymphoma in China.

PMID- 10921007
TI  - [Study of telomerase activity in colorectal carcinomas].
AB  - OBJECTIVE: To investigate the telomerase activity in human colorectal carcinoma
      and tumor-adjacent tissue and to investigate the possibility of telomerase as
      tumor biological marker. METHODS: A total of 60 human colorectal tissue
      specimens, comprising 37 carcinomas, 3 benign lesions and 20 tumor-adjacent
      tissue specimens were examined for telomerase activity by telomeric repeat
      amplification protocol(TRAP) assay. RESULTS: No telomerase activity in 20 tumor
      adjacent tissues and 3 benign lesions was detected. However, of 37 colorectal
      carcinoma specimens, 35 were positive for telomerase activity with a 94.6%
      positive rate. CONCLUSION: The data suggest that telomerase is a tumor specific
      gene marker, and may play an important role in early diagnosis and treatment of
      colorectal carcinomas.

PMID- 10921008
TI  - [Population-based cancer survival: an analysis of 16,922 cases].
AB  - OBJECTIVE: In the period of 1982-1991, 16,922 patients with cancers from 15 sites
      of Qidong population-based cancer registry were analysed for evaluation of cancer
      survival as well as different cancer control measures. METHODS: Observed survival
      rate (OS) was computed by the Kaplan-Meier method using EGRET statistical
      software package. Relative survival (RS) which is the ratio of the OS to the
      expected rate was calculated by using Qidong life table with respect to sex, age
      and calendar period of observation. RESULTS: The five-year OS for the 5 leading
      sites of cancers, liver, stomach, lung, oesophagus, and rectum were 1.8%, 11.6%,
      3.0%, 3.3%, and 19.9%, respectively. The five-year RS for the 5 sites were 1.9%,
      14.0%, 3.6%, 4.2%, and 23.7%, respectively, in which, 1.7%, 14.8%, 3.4%, 4.2%,
      and 26.0% for males, and 2.7%, 12.7%, 4.1%, 4.0%, and 22.0% for females,
      respectively. Female patients with breast cancer and cervix cancer had 5-year RS
      of 54.6% and 33.0%. CONCLUSION: Cancer survival rates for all sites are poor, in
      which that of the liver is the lowest, while that of the breast, the highest. The
      survivals of cancers for all sites, especially for breast, cervix, and leukaemia
      are seen to be lower than those of European countries except for oesophagus,
      pancreas and lung cancer which do not achieve improved survival both in
      developing and developed countries. There will be a long way to improve the total
      cancer survival, as well as the cancer treatment in the developing countries.

PMID- 10921009
TI  - [Clinical observation on the adhesion molecule expression and functional study of
      platelets in cancer patients].
AB  - OBJECTIVE: To investigate adhesion molecule expression and functional status of
      platelets in cancer patients and their relation to cancer progression. METHODS:
      Using flow cytometry to measure the expression of surface antigens and functional
      status of platelets in 50 healthy donors and 181 cancer patients. RESULTS:
      Comparing with normal donors, the expression of CD42a in cancer patients
      decreased, and that of TSP and CD36 increased. The number of platelets with CD36+
      TSP+, CD36+ TSP-, CD9+, CD31+, CD62+ CD63-, CD62+ CD63+, CD62- CD63+ phenotypes
      also increased. There was significant difference between patients in early stage
      and those in advanced stage, but there was no significant difference between the
      patients in early stage and healthy donors. The expression of CD41 did not change
      in cancer patients. CONCLUSION: In cancer patients, especially in the advanced
      stage of the disease, the expression of the adhesion molecules on platelets and
      their released products increase, indicative of an activated state of the
      platelets.

PMID- 10921010
TI  - [Two-phase dynamic CT and trans-abdominal ultrasonography for preoperative TNM
      staging of gastric carcinoma: a correlation study with surgery and pathology].
AB  - OBJECTIVE: To assess the value of two-phase dynamic CT and transabdominal
      ultrasonography in the preoperative staging of gastric carcinoma. METHODS: Two
      phase dynamic CT was performed in 63 cases of gastric carcinoma confirmed
      histologically by fibro-gastroscopic biopsy. Of the 63 cases, 20 had trans
      abdominal ultrasonography (US) immediately after CT examination. Imaging findings
      were correlated with surgical and pathologic findings. RESULTS: For evaluation of
      T and N staging, the accuracy of dynamic CT was 53.23% and 58%, respectively,
      that of CT in combination with US for T staging was 70%, which was statistically
      different from that of CT alone (P < 0.05). Accuracy of CT in combination with US
      for TNM staging was 90%, there was marked statistical difference (P < 0.05)
      compared with the accuracy of US. CONCLUSION: The major role of dynamic CT in
      combination with trans-abdominal ultrasonography for staging of gastric carcinoma
      is to ascertain whether the tumor has invaded adjacent structures-T staging,
      which is helpful in treatment planning.

PMID- 10921011
TI  - [Plasma neuropeptide Y (NPY) levels in patients with gastric and colorectal
      carcinomas].
AB  - OBJECTIVE: To investigate the plasma NPY concentration in patients with gastric
      and colorectal carcinomas in relation to tumor progression. METHODS: Blood
      samples were obtained from patients with gastric cancer (n = 18) and colorectal
      cancer (n = 20). Plasma NPY concentration was determined by radioimmunoassay.
      RESULTS: The average plasma NPY level in the 38 patients studied (125.3 +/- 31.5
      pg/ml) was significantly(P < 0.001) lower than that in 28 healthy control
      individuals (145.1 +/- 44.1 pg/ml). Decreased NPY levels were correlated with
      loss (> 3 kg) of body weight (P < 0.01) and tumor size (> 5 cm) (P < 0.05). The
      stage of gastric cancer, but not that of colorectal cancer, was negatively
      correlated with plasma NPY level. Plasma NPY level did not correlate with sex,
      age, blood pressure, depth of tumor invasion, degree of differentiation, lymph
      node metastasis, hemoglobin and albumin concentrations. CONCLUSION: Plasma NPY
      level is decreased in patients with gastric and colorectal carcinomas, but it
      reflects only in part the progression of gastric cancer.

PMID- 10921012
TI  - [Correlation study of high-resolution CT with pathologic finding of solitary
      small lung nodules].
AB  - OBJECTIVE: To correlate high resolution CT(HRCT) with pathologic findings and to
      evaluate the capability of HRCT versus conventional CT(CCT) to provide
      informations for accurate diagnosis of solitary small lung nodules. METHODS:
      Seventy-three cases (75 nodules) of solitary lesions in the lung less than 3 cm
      in diameter were examined with HRCT (64 cases had CCT) before surgery and
      correlated with histo-pathologic findings. RESULTS: In the 37 proven carcinoma,
      on HRCT, the lesions were round and oval in shape (34), deeply lobulated(28),
      with serrated margin(33), thin spiculation(37), air alveologram(19), and air
      bronchogram (10). Histologically, the tumor showed irregular growth pattern with
      interstitial fibrous proliferation and intra-tumoral residual air-containing
      spaces in alveoli and bronchioles. Intratumoral fat or calcification, satellate
      lesions, thick or long spicules, moderate or marked pleural adhesions, scallop
      shaped contour were the common findings of benign lesions. HRCT was significantly
      superior to CCT in the assessment of the intra-structure, contour and margin of
      the lesion. CONCLUSION: HRCT is recommended routinely for the evaluation of
      solitary small pulmonary nodules.

PMID- 10921013
TI  - [Primary esophageal adenocarcinoma].
AB  - OBJECTIVE: To study the clinical biocharacteristics of primary esophageal
      adenocarcinoma (PEAC) and factors influencing patients' prognosis and to find
      reasonable surgical indications and combined therapy. METHODS: To analyse the
      clinical materials of 106 patients with PEAC undergone operation compared with
      those of patients with esophageal squamous-cell carcinoma (ESCC). RESULTS: The
      overall resectability, morbidity and 30-day mortality rate of PEAC was 92.5%,
      23.5% and 2.8% respectively, similar to those of ESCC. The TNM staging, lymph
      node metastasis, extraesophageal invasion and types of operation were the major
      determinants influencing long-term prognosis. The 5-year survival rate of PEAC
      was 21.0%, which was lower than that of ESCC(P < 0.01). Metastasis or recurrence
      remained to be the cause of death in 82.4% of patients who lived longer than 5
      years, which was higher than that of ESCC(P < 0.01). Adjuvant radiation did not
      influence survival of the patients with lymph node metastasis, but appeared
      helpful to the patients with no lymph node metastasis. CONCLUSION: Compared with
      ESCC, PEAC is a malignent disease with poor prognosis. Surgical resection is the
      first and chief choice of treatment. Surgical indications include patients in
      stage 0, I, II and some in stage III and even in stage IV of PEAC. Early
      diagnosis and early treatment as well as curative operation could improve
      prognosis. Adjuvant radiation therapy appeares helpful only to the patients
      without lymph node metastasis.

PMID- 10921014
TI  - [Early postoperative intraperitoneal perfusion chemotherapy for advanced
      colorectal cancer].
AB  - OBJECTIVE: To study the effect of early postoperative intraperitoneal perfusion
      chemotherapy (IPPC) on the prevention of peritoneal recurrence and liver
      metastasis in patients with advanced colorectal cancer. METHODS: From 1990
      through 1997, 102 patients with advanced colorectal cancer were admitted. The
      tumor invaded the intestinal serosa with elevated CEA in the peritoneal fluid.
      Fifty-four of the 102 patients, beginning from the operation day, were given
      IPPC, once per day for 6 days, with warm(43-45 degrees C) sterile double
      distilled water containing 1 g 5-Fu and 10 mg MMC. The other 48 patients, as
      control, received 1 g 5-Fu and 8 mg MMC by i.v. infusion, once per day for 6
      days. In addition, oral tegafur was given to all patients with a total dose of 40
      g. RESULTS: In patients treated with IPPC, peritoneal recurrence developed in 2
      patients, liver metastasis in 2 patients whereas 12 cases had peritoneal
      recurrence and 6 had liver metastasis in patients treated by i.v. infusion. No
      complication developed in any of the treated patients. CONCLUSION: IPPC is
      effective in preventing tumor recurrence in the peritoneal cavity and metastasis
      to the liver in patients with advanced colorectal cancer. The treatment procedure
      is simple and safe.

PMID- 10921015
TI  - [Major blood vessel excision and reconstruction in the treatment of
      retroperitoneal neoplasms].
AB  - OBJECTIVE: To summarize the experience in the treatment of retroperitoneal tumors
      involving major blood vessels. METHODS: Twenty five cases with retroperitoneal
      tumors involving major blood vessels were treated by excision of the tumor and
      the major blood vessel involved followed by vascular reconstruction. RESULTS:
      After a careful preoperative evaluation and necessary preparation, the tumor
      together with the involved blood vessels in all patients are successfully
      resected and the severed major blood vessels reconstructed. There was no
      operative death. CONCLUSION: Retroperitoneal neoplasm involving major blood
      vessels is not a contraindication for surgical resection. The tumor and the
      involved vessel can be removed en bloc followed by vascular reconstruction. The
      risk of local tumor recurrence can thus be minimized and better survival
      achieved.

PMID- 10921016
TI  - [Adjuvant chemotherapy following radical surgery for non-small cell lung cancer:
      a randomized study].
AB  - OBJECTIVE: To evaluate the efficacy of adjuvant chemotherapy after radical
      surgery for non-small cell lung cancer (NSCLC). METHODS: Seventy patients with
      NSCLC(stage I-III) undergone radical surgery were randomized into two groups: 35
      patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2,
      vincristine(VCR) 1.4 mg/m2, adriamycin(ADM) 50 mg/m2, d1; cisplatin (PDD) 20
      mg/m2, d1-5, for 4 cycles, and followed by oral ftorafur (FT-207) 600-900 mg/d
      for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical
      treatment only (surgery group). RESULTS: The overall 5-year survival rate was
      48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group,
      respectively. The difference between the two groups was not statistically
      significant (P > 0.05). The 5-year survival rate of patients in atage III was
      44.0% and 20.8% (5/24) received surgery with and without adjuvant chemotherapy,
      respectively. The difference between the two groups was statistically significant
      (P < 0.025). The 5-year survival rate of patients in stage I-II in the two group
      was 60.0% and 54.5%, respectively (P > 0.75). CONCLUSION: Postoperative adjuvant
      chemotherapy in NSCLC improves survival but only in patients in stage III, it
      results in significantly higher 5-year susvival rate than surgery alone.

PMID- 10921017
TI  - [Supraglottic laryngectomy with or without one arytenoid in epiglottic carcinoma.
      A report of 40 cases].
AB  - OBJECTIVE: Supraglottic laryngectomy with or without one arytenoid is a
      functional laryngectomy suitable for treatment of epiglottic squamous carcinoma.
      This procedure consists of resection of the thyroid cartilage, epiglottis and the
      entire preepiglottic space. METHODS: Between 1990 and 1996, supraglottic
      laryngectomy was used to treat 40 patients with epiglottic carcinoma. The data
      were collected by a review of patient records and follow-up. The cancers were in
      stages T1(17), T2(17) and T4(6) according to the 1987 UICC cancer staging
      criteria. RESULTS: Twelve ipsilateral and one bilateral functional neck
      dissection were performed simultaneously of which 7 patients had metastasis in
      lymph nodes. No patient died postoperatively. Only 8(20%) had slight aspiration
      before the 20th day. All patients had decannulated. Twenty-nine cases received
      radiotherapy and chemotherapy. A follow-up analysis showed survival rate of 74%
      at 3 years. CONCLUSION: We propose supraglottic laryngectomy for the surgical
      treatment of early supraglottic carcinomas, which could acquire almost normal
      laryngeal function.

PMID- 10921018
TI  - [Clinical analysis of postoperative radiotherapy for stage I endometrial cancer].
AB  - OBJECTIVE: To evaluate the role and complications of adjuvant radiotherapy for
      stage I endometrial cancer after surgery. METHODS: From May, 1986 to December,
      1995, 20 patients with stage I endometrial cancer received total abdominal
      hysterectomy with bilateral salpingo-oophorectomy(TAH/BSO), and additional pelvic
      lymph node dissection in 5 cases. Most of the patients received radio therapy in
      2-4 weeks after surgery. The radiation fields included pelvic lymph nodes with a
      total dose of 40-50 Gy. RESULTS: All the patients had survived for 10 years. Only
      one patient developed distant metastases. Acute radiation reaction was observed
      in all patients. Late radiation-induced damage occured in six patients and was
      severe in two. CONCLUSION: Postoperative radiotherapy in the management of stage
      I endometrial cancer is beneficial for the controal of local recurrence but has
      relatively high frequency of late radiation injury.

PMID- 10921019
TI  - [Diagnosis and treatment of male breast carcinoma].
AB  - OBJECTIVE: To evaluate the diagnosis and treatment of male breast carcinoma.
      METHODS: Thirty-two male breast carcinoma cases were studied. The median age was
      fifty-four years old. The diagnosis, treatment and prognosis for male breast
      carcinoma were studied. RESULTS: Clinical stage of the patients: I, 7 patients;
      II, 17 patients; III, 7 patients; IV, 1 patient. Of the 32 carcinomas, 31
      patients had mass in the breast. Positive lymph nodes were found in 57.1% of the
      patients. The 5-year survival rate was 65.6% for all patients, 68.4% for patients
      undergone radical mastectomy, 66.7% for those undergone modified radical
      mastectomy and 57.1% for the others. CONCLUSION: The optimal treatment for male
      breast carcinoma is modified radical mastectomy combined with radiotherapy,
      chemotherapy and endocrine therapy.

PMID- 10921021
TI  - [Effects of matrine on telomerase activity and cell cycle in K562 cell].
AB  - OBJECTIVE: In order to search for new tumor differentiation inducer, the effects
      of matrine of Chinese herbal origin on differentiation of K562 cells and its
      mechanism were studied. METHODS: Telomerase activity was determined by PCR-ELISA
      in untreated or treated K562 cells, cell cycle phases were analyzed by
      fluorescence-activated cell sorter analysis. RESULTS: Telomerase activity of K562
      cells was significantly inhibited when treated with matrine, and cell cycle of
      the treated K562 cells was changed with marked decrease in S phase. CONCLUSION:
      Matrine can induce differentiation of K562 cells, the mechanism of which might be
      related to the inhibition of telomerase activity and cell cycle arrest.

PMID- 10921020
TI  - [Garlic oil induces differentiation and apoptosis of human gastric cancer cell
      line].
AB  - OBJECTIVES: To study the mechanism of garlic oil-induced differentiation of human
      gastric cancer cell line BGC-823. METHODS: Confocal microscopic assay and
      Northern blot hybridization were used to detect morphological change and gene
      expression in garlic oil treated human gastric cancer cells (BGC823). RESULTS:
      Cell growth in vitro and tumorigenicity in nude mice were inhibited dramatically
      by garlic oil. Garlic oil treatment resulted in cell apoptosis as shown by DNA
      fragmentation. High expression level of WAF1/p21 and wild type p53 gene was
      detected in garlic oil-treated cells. CONCLUSION: These data indicate that
      differentiation and apoptosis of BGC-823 cell can be induced with garlic oil, and
      p21 and p53 genes possibly play important role in the process.

PMID- 10921022
TI  - [Effect of EBV latent membrane protein 1 gene isolated from human nasopharyngeal
      carcinoma cell line SUNE on the growth of immortalized epithelial cells].
AB  - OBJECTIVE: To study the effect of EBV latent membrane protein (LMP1) gene
      isolated from human nasopharyngeal carcinoma cell line SUNE on the growth of
      epithelial cells and the role of LMP1 in the genesis of nasopharyngeal
      carcinomas. METHODS: EBV LMP1 gene eukaryotic expression plasmid was transfected
      into human embryo kideney epitheial cells. Expression of LMP1 protein in the
      transfected cells was detected. Dynamic cell growth status, growth rate, ability
      of colony formation in soft agar and the tumorigenicity of the transfected cells
      in nude mice were studied. RESULTS: The LMP1 gene transfected cells grew
      vigorously and rapidly, lost contact inhibition, formed more colonies in soft
      agar, developed tumors in nude mice. CONCLUSION: LMP1 gene could alter the
      biological behaviours of epithelial cells, promote cell proliferation and
      transformation, and endows the transfected cells with growth characteristics like
      tumor cells.

PMID- 10921023
TI  - [Rejection of non-immunogenic tumor cells transfected with costimulatory molecule
      B7 after treatment with IFN-gamma in vitro].
AB  - OBJECTIVE: To explore immuno-gene-therapy of non-immunogenic tumor. METHODS: Non
      immurogenic tumor cells B16 were transfected with B7-1 gene. The B7-1 gene
      transfected B16 cells (B7+ B16) were treated with recombinant murine interferon
      gamma (rmIFN-gamma) in vitro, and then inoculated to C57BL/6 mice. RESULTS: While
      B7+ B16 cells grew progressively in syngeneic mice, tumorigenicty was
      significantly reduced when B7+ B16 cells were treated with rmIFN-gamma before
      inoculation to mice. Flow cytometric analysis of the rmIFN-gamma treated B7+ B16
      cells showed significant up-regulation of MHC class I expression. CONCLUSION: For
      non-immunogenic tumor if the expressions of MHC class I molecules is low,
      providing co-stimulatory molecule B7 is not enough to reduce tumorigenicity. The
      B7-1 gene transfected B16 cells become non-tumorigenic or weakly tumorigenic when
      their MHC class I is up-regulated.

PMID- 10921024
TI  - [Construction of PCNA antisense RNA expression vector and its antitumorigenic
      effect on human gastric cancer cell].
AB  - OBJECTIVE: To observe the effect of proliferating cell nuclear antigen (PCNA)
      antisense RNA on the growth characteristics of human gastric cancer cell.
      METHODS: An eukaryotic expression vector pDR-PCNA with human PCNA gene insert in
      reverse direction was successfully constructed. The human gastric cancer cell
      line SGC-7901 was transfected with pDR-PCNA by lipofectamine. RESULTS: Growth
      rate, protein and RNA biosynthesis and DNA contents in S-phase and G2/M-phase of
      the transfected SGC-7901 were significantly suppressed in comparison with those
      of the parental cell line. CONCLUSION: PCNA antisense RNA can significantly
      suppress the in vitro growth of gastric cancer cell line.

PMID- 10921025
TI  - [Inhibition of apoptosis by bcr-abl fusion gene in K562 cells].
AB  - OBJECTIVE: To investigate the effect of bcr-abl fusion gene on CML cell
      apoptosis. METHODS: Apoptosis of in vitro cultured K562 cells was observed after
      exposure to synthetic 18-mer antisense oligodeoxynucleotide complementary to the
      bcr-abl junction (b3a2). RESULTS: Apoptosis of K562 cells was significantly
      increased associated with inhibition of bcr-abl expression. CONCLUSION: bcr-abl
      fusion gene formation due to chromosome translocation may be the major mechanism
      of CML via inhibition of apoptosis.

PMID- 10921026
TI  - [Northern blot analysis of nm23 gene expression in human lung cancer].
AB  - OBJECTIVE: To investigate the role of nm23 gene expression in lung cancer.
      METHODS: Forty human lung cancer tissues and 19 non-cancerous pulmonary tissues
      were studied for their nm23-H1 and nm23-H2 mRNA expression with nonradioactive
      Northern blot hybridization. Correlation of nm23 mRNA expression with clinical
      features of lung cancer was analyzed. RESULTS: The mRNA expression of nm23-H2
      gene in poorly differentiated squamous-cell carcinoma was significantly decreased
      compared to that in moderately differentiated squamous-cell carcinoma. The mRNA
      expression of nm23-H1 and nm23-H2 genes in small cell lung cancer was decreased
      compared to that in squamous-cell carcinoma. No significant difference in nm23
      mRNA expression was observed in lung cancers with and without lymph node
      metastasis, nor was there significant difference in patients with lung cancers in
      different stages. CONCLUSION: The mRNA expression of nm23 gene is correlated with
      the degree of differentiation of lung cancer, but there is no evidence of
      metastasis suppression effect by nm23 gene.

PMID- 10921027
TI  - [Expression of signal-regulatory protein alpha (SIRP alpha) in hepatocellular
      carcinoma].
AB  - OBJECTIVE: To investigate the association between signal-regulatory protein alpha
      (SIRP alpha) and hepatocellular carcinoma (HCC). METHODS: Thirty-six pairs of HCC
      and the surrounding noncancerous hepatic tissues, one normal liver cell line and
      4 HCC cell lines were used to extract the total RNA and then to prepare the mRNA.
      The expression of SIRP alpha was determined by Northern blot analysis. The
      results were analyzed in association with the pathologic characteristics of each
      sample. RESULTS: SIRP alpha expressed at low level in 20 of 36 HCC samples and 2
      of 4 HCC cell lines. Of the two major hybridization signals, a 3.9 kb transcript
      in HCC samples was 2-4 times lower than that in the surrounding noncancerous
      hepatic tissues, whereas a 2.5 kb transcript was 4-6 times as low. Furthermore, a
      hybridization signal slightly longer than 3.9 kb, being absent in the surrounding
      noncancerous hepatic tissue, appeared in 9 of the 20 HCC samples. Low level
      expression of SIRP alpha was observed in all of the 5 HCC samples that had
      intrahepatic or portal metastasis. CONCLUSION: The expression of SIRP alpha,
      especially 2.5 kb transcript, was down-regulated in HCC, and an unknown mumber or
      a variant of SIRP family existed in some tumor tissues. SIRP alpha protein may
      play an important role in hepatic oncogenesis and metastasis of HCC.

PMID- 10921028
TI  - [Mutation of APC gene in sporadic colorectal tumors].
AB  - OBJECTIVE: To investigate mutation of APC gene in sporadic colorectal tumors.
      METHODS: Thirty-six samples of colorectal cancer and twenty-eight samples of
      colorectal polyps resected by operation and endoscopy were collected. As control,
      normal mucosal tissues in patients with cancer were taken from site 10 cm away
      from cancer. Three familial adenomatous polyposis (FAP) patients were also
      included in this study. The mutation cluster region (MCR) within exon 15 of APC
      gene was amplified by PCR and the PCR products were subject to SSCP analysis.
      Three mutant DNA fragments screned by PCR-SSCP were sequenced. RESULTS: No
      mutation in MCR of APC gene was found in normal mucosa, inflammatory polyp and
      hyperplastic polyp. Mutation in MCR of APC gene was found in 7 of 28 cases with
      sporadic colorectal polyps and in 11 of 36 cases with colorectal carcinomas. The
      difference in mutation frequency between adenomatous group (including FAP, 31.0%)
      and carcinomatous group(including FAP, 35.9%) was not statistically significant
      (P > 0.05). Mutation of APC gene was detected in two of three FAP patients. The
      same point mutation of codon 1,425 was found in both adenoma tissue and its
      hepatic metastasis in one FAP patient by DNA sequencing. CONCLUSION: Mutation of
      APC gene occurs not only in FAP, but also in sporadic colorectal tumors. It takes
      part in the development of most, if not all, sporadic colorectal carcinomas.

PMID- 10921029
TI  - [The effect of ectopic HCG on microvessel density in gastric carcinoma].
AB  - OBJECTIVES: To study the effect of ectopic HCG on microvessel density in gastric
      carcinoma using immunohistochemical staining with anti-beta-HCG polyclonal
      antibody and anti-factor VIII related antigen(FVIII RAg)antibody. METHODS: A
      total of 40 specimens resected from patients with gastric carcinoma was
      investigated by immunohistochemical staining with a anti-beta-HCG polyclonal
      antibody and a monoclonal antibody against FVIII RAg. The expression of beta-HCG
      and the microvessel density(the average number of microvessel in three areas of
      highest vascular density at 400 x magnification) in various regions of the
      histologic specimens were studied. RESULTS: Fifteen (37.5%) of the 40 gastric
      carcinomas was positive for beta-HCG protein in tumor tissue. beta-HCG protein
      was negative in the tumor-adjacent and in normal tissue. The mean microvessel
      density was 27.4 +/- 7.1 in the tumor, 11.9 +/- 5.4 in tumor-adjacent and 4.8 +/-
      1.5 in normal tissues (P < 0.05-0.01). There was a close correlation with beta
      HCG positivity and microvessel density (MVD). There was no correlation between
      the degree of tumor cell differentiation and beta-HCG expression, nor was a
      correlation between it and MVD. High expression level of beta-HCG and MVD was
      significantly associated with hematogenous metastases. CONCLUSION: Ectopic HCG
      expression may have angiogenic effect which, in turn, may facilitate hematogenous
      dissemination of gastric cancer.

PMID- 10921030
TI  - [The relationship between hepatocellular carcinoma and hepatitis C virus
      infection in Guangxi, China].
AB  - OBJECTIVE: To study the significance of HCV infection as a risk factor for
      hepatocellular carcinoma (HCC) in Guangxi. METHODS: Monoclonal antibodies against
      the core, NS3 and NS4 region of HCV, and anti-HBsAg antibody were used for
      immunohistochemical staining. RESULTS: The frequency of HCV infection from
      regions with high, intermediate and low prevalence of HCC was 24/63(38.1%), 23/62
      (37.1%) and 30/77(39.0%), respectively, while that of HBsAg was 84.1%, 83.8% and
      84.4%, respectively. The overall positive rate of HCV infection was 77/202
      (38.1%), and of HBV infection was 170/202 (84.2%). CONCLUSION: While HBV
      infection frequently accompanies HCC, HCV infection is present in more than 1/3
      of HCC. This is generally the case regardless of geographical difference in HCC
      prevalence.

PMID- 10921031
TI  - [Expression and significance of interleukin 6, interleukin 8 and their receptors
      in acute promyelocytic leukemia during all-trans retinoic acid induction
      treatment].
AB  - OBJECTIVE: To evaluate the expression and clinical significance of interleukin 6,
      soluble glycoprotein 130 (sgp 130), interleukin 8 and type A interleukin 8
      receptor (IL-8RA) in acute promyelocytic leukemia (APL) patients during all-trans
      retinoic acid (ATRA) treatment. METHODS: Serum and bone marrow mononuclear cell
      (MNC) culture supernatant IL-6, sgp 130, IL-8 concentrations of 18 cases APL
      patients were measured (ELISA). Bone marrow MNC IL-8RA was measured by flow
      cytometry after cultured with ATRA (10(-6) mmol/L). RESULTS: Serum IL-6, sgp130,
      IL-8 levels were higher than normal (P < 0.05), IL-6, sgp130 levels correlated
      with white blood cell (WBC) counts (P < 0.05) while IL-8 level correlated with
      body temperature (P < 0.05) at initial diagnosis after 72-hour incubation with
      ATRA, concentration of IL-6 of bone marrow MNC culture supenatant did not change,
      that of sgp130 mildly decreased, and IL-8 significantly decreased while the
      positive rate of IL-8RA on bone marrow MNC increased. During ATRA treatment,
      serum IL-6 changes were correlated with WBC changes. Peak level of IL-6 and WBC
      was lower in patients received intermittent therapy than continuous therapy.
      Serum IL-6 and IL-8 increased when complicated with infection and increase in IL
      8 seemed more sensitive. CONCLUSION: Serum levels of IL-6, sgp130, IL-8 may
      reflect patient's responsiveness to ATRA treatment, predict hyperleukocytosis and
      intercurrent infection. ATRA induces APL cell differentiation possibly via gp130
      signal transduction.

PMID- 10921032
TI  - [Study on the correlation between CT features and expression of p53 protein and
      PCNA in peripheral lung cancer].
AB  - OBJECTIVE: To investigate the correlation between CT features and expression of
      p53 protein and PCNA in peripheral lung cancer. METHODS: The expression of p53
      protein and PCNA was examined by means of SP immunohistochemical technique in 32
      cases of peripheral lung cancer proved by pathology; the relationship between the
      results and preoperative CT features was analyzed retrospectively. RESULTS: The
      expression of p53 protein and PCNA was correlated with tumor size, deep
      lobulation, frank cavitation, pleural indentation and mediastinal lymph node
      metastasis, but not with spiculation. CONCLUSION: The CT features of peripheral
      lung cancer with diameter more than 3 cm, deep lobulation, frank cavitation,
      pleural indentation or mediastinal lymph node metastasis indicate higher degree
      of malignancy and proliferative activity of tumor cells.

PMID- 10921033
TI  - [Bcl-2 gene expression in endometrial carcinoma].
AB  - OBJECTIVE: To evaluate the relationship between bcl-2 gene and endometrial
      carcinoma. METHODS: Immunohistochemical staining was performed on formalin-fixed
      paraffin-embedded tissue sections. A monoclonal antibody to the bcl-2 gene
      product was used, the signal was detected using a streptavidin-biotin complex
      with aminoethylcarbazole. There were 15 cases of endometrial atypical hyperplasia
      and 50 cases of endometrial carcinoma examined. RESULTS: Bcl-2 expression was
      high in endometrial atypical hyperplasia, whereas bcl-2 expression was low in
      endometrial carcinoma. In endometrial carcinoma, with progression of clinical
      stage, decreased histologic grade and deepening of cancer invasion, the positive
      rate of bcl-2 expression was correspondingly decreased. CONCLUSION: Bcl-2 plays a
      role in the genesis of endometrial carcinoma especially at the initial stage.

PMID- 10921034
TI  - [c-erbB2 gene amplification in human primary epithelial ovarian cancer and its
      clinical significance].
AB  - OBJECTIVE: To study c-erbB2 gene amplification in human primary epithelial
      ovarian cancer and its clinical significance. METHODS: One hundred forty nine
      samples of primary epithelial ovarian tumors, including 34 beign tumors, 7
      borderline tumors and 108 carcinoma, were studied for c-erbB2 gene amplification
      by Southern blot analysis. RESULTS: c-erbB2 gene amplification was detected in 35
      (32.4%) of the 108 cases with primaey epithelial ovarian carcinoma, while all
      cases with beign tumors and borderline lesions were negative (P < 0.001). There
      was a strong correlation between c-erbB2 gene amplification and FIGO stage of
      human ovarian carcinoma (P = 0.026), degree of cell differentiation (P = 0.011)
      and the size of residual tumor (P < 0.001). Univariate and multivariate analysis
      showed that c-erbB2 gene amplification was an independent prognostic factor. The
      average 3-year survival rate was 28.4% in patients with gene amplification and
      57.7% in patients without gene amplification(P = 0.016). CONCLUSION: c-erbB2 gene
      amplification occurs almost in 1/3 of the patients with ovarian carcinoma
      examined. Ovarian carcinoma with c-erbB2 gene amplification is highly malignant
      and associated with poor prognosis.

PMID- 10921035
TI  - [Clinical significance of P-glycoprotein expression in breast cancer].
AB  - OBJECTIVE: To study the clinical significance of P-glycoprotein (P-gp) in breast
      cancer. METHODS: Expression of P-gp in 60 cases of breast cancer was examined by
      immunohistochemistry. P-gp expression and response to chemotherapy were
      comparatively investigated in 19 patients with metastatic breast cancer. RESULTS:
      The P-gp was positive in 48.3% of the 60 cases of breast cancer. P-gp expression
      was not related to patients' age, menstruation status, number of axillary lymph
      nodes involved, clinical stage, histological type, and hormonal receptor status(P
      > 0.05). The frequency of metastasis (62.1%) and mortality (51.7%) were higher in
      P-gp positive cases than those in negative cases (16.1% vs 12.9%, P < 0.005). The
      5-year survival rate of P-gp positive cases (48.3%) was significantly lower than
      that of negative cases (87.1%) (P < 0.05). In patients received adjuvant
      chemotherapy distant metastasis occurred more frequently in P-gp positive cases
      (94.7%) than in P-gp negative cases (57.1%) (P = 0.0468). More P-gp negative
      patients (7/9) than positive patients (1/10) were responsive to chemotherapy (P =
      0.0055). CONCLUSION: Immunohistochemical examination of P-gp expression is useful
      in predicting response to chemotherapy and prognosis in breast cancer patients. P
      gp positivity is associated with poor prognosis.

PMID- 10921036
TI  - [Two-phase dynamic CT findings of gastric carcinoma and its value for tumor
      detection and gross classification].
AB  - OBJECTIVE: To analyze the two-phase dynamic CT features of gastric carcinoma and
      to assess its usefulness for tumor detection and gross classification. METHODS:
      Two-phase dynamic CT was performed in 63 cases of gastric carcinoma proved
      histologically by fibro-gastroscopic biopsy. CT features of gastric carcinoma,
      tumor detection, and gross classification were correlated with surgical and
      pathologic findings. RESULTS: The detectability by two-phase enhanced CT scanning
      of early and advanced gastric carcinoma was 100% and 98.2%, respectively. The
      overall accuracy of gross classification for advanced carcinoma was 65.4%, but
      for early gastric carcinoma, it was 0. The accuracy of Borrmann type II, III, IV
      was 85.7%, 100%, 55.6%, respectively. In the first phase (early enhancing phase)
      CT scan, the manifestation of early gastric carcinoma included local thickening
      of gastric wall, moderate or marked heterogeneous enhancement of lesions in 4
      cases and mild enhancement in the other 4 cases. Local or extensive thickening of
      gastric wall, with or without ulceration, moderate or marked heterogeneous
      enhancement in early enhancing phase were shown in advanced gastric carcinoma. In
      the second phase, the degree of tumor enhancement in advanced carcinoma was
      slightly higher than that of the normal part of gastric wall. There were 4 cases
      with mucinous adenocarcinoma, a target or laminary appearance was present in 3
      cases, and intramural calcification was present in 2 cases. CONCLUSION: 1.
      Enhanced dynamic CT scan plays a significant role in the diagnosis of gastric
      carcinoma, early enhancing phase scanning is the technique of choice nowadays for
      demonstrating tumor lesions. 2. Sophisticated scanning technique is mandatory in
      improving the diagnostic accuracy of gastric carcinoma.

PMID- 10921037
TI  - [The value of MRI for diagnosis of recurrence of rectal carcinoma after surgical
      resection].
AB  - OBJECTIVE: To define the possible role of magnetic resonance imaging (MRI) for
      diagnosis of local recurrence of rectal carcinoma. METHODS: Pelvic MRI scans of
      34 patients with rectal carcinoma received surgical resection were reviewed. SE
      sequence: Axial T1WI, T2WI and sagittal T1WI scanning of pelvis were performed.
      Two patients had Gd-DTPA enhancement. RESULTS: Of the 34 patients 27 developed
      recurrence. The major MRI findings were: tumor mass in the sacro-anterior and
      perineal regions, T1WI with low signal intensity, T2WI with mixed but slightly
      high signal intensity, and discontinuity or loss of sacro-anterior fat space on
      sagittal T1WI. Cancer invasion could be detected to urinary bladder in 8
      patients, to prostate in 6 patients, to sacrum in 6 patiens. Pelvic lymph node
      enlargement was seen in 3 patients. Seven patients did not show any signs of
      tumor recurrence. CONCLUSION: Routine follow-up MRI scan after rectal carcinoma
      resection is useful in revealing recurrence of cancer and its extent of
      involvement.

PMID- 10921038
TI  - [Analysis of X-ray images of giant-cell tumor of bone of rare locations].
AB  - OBJECTIVE: To analyse X-ray images of giant-cell tumor of rare locations.
      METHODS: To retrospectively review the X-ray films, CT scans and arteriograms of
      48 cases of surgically and/or pathologically confirmed giant-cell tumor of bone
      of rare locations. RESULTS: Of the 48 cases, expansive cystic destructive changes
      of the bone with soap-bubble like appearence was found in 30 cases, osteolytic
      destruction in 10 cases, soft tissue mass outside of bone with sinking,
      flattening and local expanding of bone in 4 cases, invading into neighboring bone
      in 4 cases, hyperplasia and sclerosis of bone in 3 cases and staining of abnormal
      blood vessels and tumors in 3 cases. CONCLUSION: For the diagnosis of giant-cell
      tumor of bone of rare locations, X-ray plain film is of great value. CT is even
      better than plain film; arteriogram is helpful for diagnosis and treatment
      planning.

PMID- 10921039
TI  - [Normal-sized ovary carcinoma syndrome--clinical and pathological analysis of 11
      cases].
AB  - OBJECTIVE: To evaluate clinical-pathologic features, diagnostic criteria,
      effective treatment and prognosis of a clinically rare "normal-sized ovary
      carcinoma syndrome". METHODS: Histologic slides of 11 cases from 1984 to 1993 of
      normal-sized ovary carcinoma syndrome were retrospectively reviewed. Seven of the
      11 cases were extraovarian peritoneal serous papillary carcinoma (EPSPC). The
      remaining 4 cases were serous adenocarcinoma of the ovary (2 cases), malignant
      mesothelioma (1 case) and metastatic poorly differentiated adenocarcinoma of
      unknown origin (1 case). All patients received relatively thorough surgical
      resection combined with multiple courses of adjuvant chemotherapy. RESULTS: The
      patient with malignant mesothelioma survived for 90 months, one case with EPSPC
      survived for 87 months up to Dec 1997. The average survival time of 9 patients
      who died of their diseases was 17.8 months, being longer than that reported in
      the literature. CONCLUSION: Following accurate diagnosis of normal-sized ovary
      carcinoma syndrome, radical tumor resection is the first treatment of choice. For
      residual tumor, postoperative chemotherapy or radiotherapy is essential to obtain
      better prognosis.

PMID- 10921040
TI  - [Clinical analysis of 19 patients with pleural mesothelioma].
AB  - OBJECTIVE: To summarize the experience in the diagnosis of pleural mesothelioma.
      METHODS: Analysing the clinical data of 19 patients with pleural mesothelioma,
      including age, history of exposure to asbestos, clinical manifestations, imaging
      and laboratory examinations and metastases. RESULTS: None of the 19 patients had
      history of exposure to asbestos. Eight cases(42.1%) had no obvious thoracodynia,
      9 cases(47.4%) had pleural effusion limited to the right chest, and in 2
      cases(10.5%) the brachialis plexus was involved, and in 1 case (5.3%) malignant
      mesothelial cells were detected in the pleural effusion. Pleural thickening or
      nodules were found in 13 cases on CT and in 9 cases by B ultrasonographic
      examination. CONCLUSION: Exposure to asbestos is not the only cause of pleural
      mesothelioma. Chest pain is not always associated with pleural mesothelioma. CT
      and B ultrasonography are of good help in the diagnosis of pleural mesothelioma.

PMID- 10921041
TI  - [The clinical value of intraoperative ultrasound of the liver].
AB  - OBJECTIVE: To evaluate usefulness of intraoperative ultrasound of the liver.
      METHODS: A 5.0 MHz ultrasound transducer was used to detect liver lesions, their
      number, location and relation to the intrahepatic blood vessels. RESULTS: Forty
      two patients with primary liver tumors received intraoperative ultrasonographic
      examination. Liver tumor was resected in 29 patients(69.0%). The tumors in 4
      patients were unresectable due to their close relationship to the hepatic
      vasculature as judged by the ultrasound image. Multiple lesions were found in 6
      patients during operation. CONCLUSIONS: Intraoperative ultrasound of the liver is
      sensitive enough to detect most liver lesions and to locate them by liver segment
      which makes radical tumor resection possible. It is useful to define the tumor in
      relation to hepatic vasculature. It can compensate for missing lesions in
      preoperative imaging studies. Fenestration operation for liver abscess and
      intervention treatment for liver cysts can be performed during operation.

PMID- 10921042
TI  - [Transcatheter arterial chemo-embolization combined with CT-guided percutaneous
      intratumoral injection of lipiodol-ethanol for the treatment of primary
      hepatocellular carcinoma].
AB  - OBJECTIVE: To study the therapeutic effect of transcatheter arterial
      chemoembolization (TACE) combined with CT-guided percutaneous intratumoral
      injection of lipiodol-ethanol(ITLE) for primory hepatocellular carcinoma.
      METHODS: One hundred and two patients with primary hepatocellular carcinoma (PHC)
      were divided into two groups. In group A, 52 patients treated with TACE, and in
      group B, 50 patients were treated with TACE and ITLE. RESULTS: In group A 1-, 2-,
      and 3-year survival rate of the treated patients was 68.3%, 41.2%, and 21.4%,
      respectively. Histologic examination of cancer specimens obtained from
      hepatectomy and biopsy showed that TACE caused complete necrosis in only 26.1% of
      the treated cases. In contrast, in group B patients treated with TACE combined
      with ITLE, the 1-, 2-, and 3-year survival rate was 100%, 85.2% and 68.4%,
      respectively. Combination therapy resulted in complete histologic necroses in
      86.4% of the treated cases. CONCLUSION: The therapeutic effect of TACE combined
      with CT-guided ITLE is much better than that of TACE alone.

PMID- 10921043
TI  - [Radiotherapy combined with intervention treatment for patients with advanced
      cancer: a randomized study in 60 cases].
AB  - OBJECTIVE: To study methods of treatment for advanced cancers. METHODS: From
      January 1996 to March 1997, 60 patients with advanced cancers whose life
      expectancy was 3-6 months were randomly divided into two groups. The method of
      radiotherapy was the same in the two groups, with a dose of DT50Gy/25f/5wk for
      intra-abdomanal cancers while DT60Gy/30f/6wk for those in the other regions. In
      the combination treatment group, in addition to radiation, interventional therapy
      with chemotherapeutic drugs, biological response modifiers or Chinese medicinal
      herbs was employed. RESULTS: The response rate, mean remission period, median
      survival time and 1-year survival rate in the combination treatment group was
      98.3%, 7.4 months, 11 months and 46.7%, respectively. All these were
      significantly different from those in the group of patients treated with
      radiation alone. (63.6%, 4.7 months, 6.5 months and 6.7%, respectively, P <
      0.01). CONCLUSION: Radiotherapy combined with intervention treatment can prolong
      the survival time and improve quality of life in patients with advanced cancer.

PMID- 10921044
TI  - [Establishment of two human esophageal carcinoma cell lines and their cytogenetic
      analysis].
AB  - OBJECTIVE: To explore the relation between chromosomal aberration and
      carcinogenesis of the esophagus by molecular cytogenetic analysis of two
      esophageal carcinoma cell lines. METHODS: Small tissue blocks taken from resected
      specimens of patients with esophageal cancer (EC) were cultured in medium 199
      added with 1.5% fetal bovine serun, and two esophageal carcinoma cell lines,
      EC8712 and EC8733, were established in 1987. They grew in monolayers. Molecular
      cytogenetic studies were performed on the two cell lines using chromosome G
      banding, fluorescence in situ hybridization (FISH) and comparative gene
      hybridization (CGH) techniques. RESULTS: Both cell lines were aneuploid. Loss of
      chromosome Y, partial deletion of 1p, translocation of 2q and amplification of
      5p, were observed in the 2 cell lines. Amplification of 8q and 13q in EC8733 and
      deletion of 17p in EC8712 were detected. CONCLUSION: The presene of the reported
      chromosomal aberrations may be related to the carcinogenesis and cancer
      development of the esophagus.

PMID- 10921045
TI  - [Deletion of MTS1/p16 gene in human esophageal carcinoma].
AB  - OBJECTIVE: To investigate the alteration of MTS1/p16 gene in human esophageal
      carcinoma. METHODS: A total of 60 human esophageal tissue specimens, comprising
      30 squamous-cell carcinomas and 30 tumor-adjacent tissue specimens, were examined
      for homozygous deletion of p16 gene by using Southern blot hybridization and PCR
      method. RESULTS: The results showed that no deletions were detected in 30 tumor
      adjacent tissue samples. However, of 30 esophageal carcinoma specimens, 7 were
      found negative for p16 gene in Southern blot assay, and the deletion of the p16
      gene in 5 samples were confirmed by PCR with a 16.7% p16 gene deletion rate.
      CONCLUSION: These data suggest that MTS1/p16 gene alterations may play a role in
      the progression of human esophageal carcinoma.

PMID- 10921046
TI  - [Expression of vascular endothelial growth factor correlates with invasion and
      metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To study the relationship between the expression of vascular
      endothelial growth factor (VEGF) mRNA and invasion and metastasis of
      hepatocellular carcinoma (HCC), and explore new approaches to prevent and inhibit
      recurrence and metastasis of HCC. METHODS: Surgical samples of 43 patients with
      HCC were studied using reverse transcription-polymerase chain reaction (RT-PCR).
      The relative level of VEGF mRNA expression was measured by determining a ratio of
      PCR products of VEGF to that of beta-actin gene. RESULTS: (1) Expression of VEGF
      mRNA expression in tumor tissue was found in 79.1% (34/43) of patients, whereas
      it was seen in 20.9% (9/43) of the nontumorous liver tissue. (2) The level of
      VEGF mRNA expression in tumors with tumor emboli or in non-encapsulated tumors
      was higher than that without tumor emboli or in well-encapsulated tumors (P <
      0.05). (3) There was no significant difference in the expression of VEGF mRNA
      between large HCC (diameter > 5 cm) and small HCC (diameter < or = 5 cm) (P >
      0.05). CONCLUSION: VEGF may play an important role in the invasion and metastasis
      of HCC. Angiogenesis in tumor correlates with the progression of HCC.

PMID- 10921047
TI  - [Relationships between intrahepatic metastasis of hepatocellular carcinoma and in
      situ microenvironment, and the abundance of nm23-H1 H-ras mRNA].
AB  - OBJECTIVE: To reveal intrahepatic metastasis of hepatocellular carcinoma (HCC) in
      relation to its micro-environment and nm23-H1 H-ras mRNA expression. METHODS: In
      HCC specimens from 25 patients, the level of nm23-H1 and H-ras mRNA was examined
      by quantitative reverse transcription-polymerase chain reaction(RT-PCR). Tumor
      microvessel density(MDV), an essential factor of microenvironment and
      proliferating cell nucleus antigen (PCNA), an index of tumor cell proliferation,
      were also studied by immunohistochemical methods using antibodies against
      endothelial protein factor VIII-related antigen(F8RA) and antibody PC-10.
      RESULTS: The MDV and PCNA index in the group with intrahepatic metastasis were
      remarkably higher than those in the group without it (P < 0.01), while nm23-H1
      mRNA expression level was negatively correlated with PCNA index (P < 0.05). The
      level of H-ras mRNA expression did not correlate with intrahepatic metastasis.
      MDV was positively correlated with PCNA index (P < 0.01). CONCLUSION:
      Intrahepatic metastasis of HCC depends very much on its in situ microenvironment.
      The decline in nm23-H1 mRNA may implicate a preferential proliferation of nm23
      negetive HCC cells with highly metastastic potential which adapt well to the
      microenvironment.

PMID- 10921048
TI  - [Universal presence of HBVx gene and its close association with hotspot mutation
      of p53 gene in hepatocellular carcinoma of prevalent area in China].
AB  - OBJECTIVE: Hepatitis B virus (HBV) is a major etiological agent of hepatocellular
      carcinoma (HCC). The x gene of HBV genome (HBVx) is considered as its oncogene.
      In order to assess the extent of its involvement in hepatocarcinogenesis, both
      HBsAg sero-positive and mainly sero-negative HCC were searched for the presence,
      expression and mutation status of the x gene of HBV, as well as its association
      with 249 codon hot spot mutation of p53 gene. METHODS: Using PCR, RT-PCR, PCR
      RFLP and DNA sequencing, studies were more focused on 25 HBsAg sero-negative,
      pathologically diagnosed HCC patients operated during 1991 to 1996 mainly in
      Qidong and also in Beijing. RESULTS: The x gene sequence of HBV was found by PCR
      without exception in all 25 seronegative HCC DNA (100% 25/25) and also in all 19
      seropositive counterparts. The RNA messages of HBVx gene were found in all 8 HCC
      patients randomly selected from the seronegative group. Sequence analysis of the
      HBVx gene showed the presence of missense mutation in the 130 and 131 codon in 4
      of 6 samples studied. Using PCR-RFLP, missense mutation of the 249 codon was
      identified in 57% (12/21) of all HBsAg negative cases from Qidong. No such
      mutations were found in the 4 Beijing counterparts. CONCLUSION: HBVx gene
      sequence was universally present in HBsAg negative HCC samples of Qidog studied,
      indicating the important role of HBVx gene in hepatocarcinogenesis of the high
      incidence area. The close association of the hotspot mutation of p53 gene in
      Qidong HCC with the presence of HBVx gene sequence suggests that such mutation is
      the molecular footprint of the combined effect of aflatoxin B1 exposure and HBVx
      gene product.

PMID- 10921050
TI  - [Apoptosis of B lymphocytic leukemia induced by anticancer drugs and their cell
      cycle specificity].
AB  - OBJECTIVE: Evaluating the effect of apoptosis induced by anticancer drugs on
      human B lymphocytic leukemia cell lines (Nalm-6) and their cell cycle
      specificity. METHODS: Nalm-6 cells were treated with various anticancer drugs for
      8-24 hours. Apoptotic cells and their cell cycle specificity were measured by
      using hypodiploid DNA-FCM and TdT assay + DNA staining. RESULTS: ADR, VP16, CPT,
      MTX, Ara-C could markedly induce apoptosis of Nalm-6 cells in S phase. CPM, PRD,
      6MP were less capable of inducing apoptosis. CPM in high dose resulted in cell
      necrosis. PRD induced apoptosis in G1 phase, while 6MP induced apoptosis in G1
      and S phase. The effect of CPM showed no marked cell cycle specificity.
      CONCLUSION: Hypodiploid DNA-FCM and TdT assay + DNA staining can be used to
      detect both tumor cell apoptosis and their cell cycle specificity which is
      helpful to predict prognosis and to design new chemotherapy regimen.

PMID- 10921049
TI  - [Preliminary studies of apoptotic cell-associated antigens on hepatoma].
AB  - OBJECTIVE: To analyse antigens transiently expressed on hepatoma cells during
      apoptotic response. METHODS: Hepatoma HCC9204 cells were treated with 6% ethanol
      for 6 hr to induce apoptosis. Apoptotic HCC9204 cells were isolated and
      homogenized. After centrifugation at 14,000 rpm, the supernatant was dialyzed
      against water with molecular weight cutoff at 12,000. The dialysate was used as
      hepatoma apoptotic cell-associated antigen (HACAA). Subtractive immunization
      technique was used to prepare polyclonal antibodies against apoptotic cell
      associated antigens on hepatoma. The antibody response to HACAA was determined by
      ELISA and immunoblot assays. Localization of HACAA on hepatoma apoptotic cells
      was demonstrated immunocytochemically. RESULTS: This polyclonal antibody reacted
      more strongly with HACAA than with antigen likewise prepared from non-apoptotic
      hepatoma cell. The antigenic determinants were sensitive to trypsin and mainly
      located on the cytoplasmic membrane. CONCLUSION: Epitopes are expressed on
      hepatoma apoptotic cells which can be used to examine an apoptotic response. The
      antibody reported in this paper is useful to screen novel apoptosis associated
      genes.

PMID- 10921051
TI  - [Effect of up-regulation of S-AdoMet synthetase on taxol-induced apoptosis in
      human breast cancer cells].
AB  - OBJECTIVE: To investigate the gene regulation of taxol-induced apoptosis.
      METHODS: Northern blot hybridization, enzyme activity assay of S-AdoMet
      synthetase and flow cytometry were performed in the investigation of expression
      in the mRNA level and biological action of S-AdoMet synthetase in taxol-induced
      apoptosis in human breast cancer cell line (BCap 37). RESULTS: Up-regulation of S
      AdoMet synthetase expression was resulted by taxol treatment and the expression
      peaked at 48 hours. Moreover, the up-regulation of S-AdoMet synthetase was
      associated with cytotoxicity of antimicrotubule agents including taxol and
      colchicine. Inhibition rate of S-AdoMet synthetase activity by 1% DMSO was 34% in
      taxol-treated cells and 14% in taxol-untreated cells compared to control groups,
      respectively. Posttreatment with 1% DMSO following pretreatment with individual
      antitumor agent for 3 hr promoted apoptotic cell death of taxol-, colchicine-,
      and adriamycin-treated BCap37 cells. CONCLUSION: The induction of apoptosis
      enhanced by post-treatment with DMSO in taxol-treated cells is probably linked to
      its inhibition on enzyme activity of S-AdoMet synthetase, suggesting that the
      increased expression of S-AdoMet synthetase possibly plays an important role in
      protecting cells from DNA fragmentation in taxol-induced apoptosis.

PMID- 10921052
TI  - [Induction of apoptosis in human gastric carcinoma cell line MGC-803 by
      monoclonal antibody PD4].
AB  - OBJECTIVE: To examine if monoclonal antibody PD4 (McAb PD4) which identifies a
      surface antigen of 40 kD (P40) expressed in gastric carcinoma cells could induce
      tumor cell apoptosis. METHODS: The antibody was tested for its effect on cell
      cycle and cell injury in gastric carcinoma cell MGC-803 by flow cytometry, DNA
      electrophoresis and TdT assay. Fas antigen expression in MGC-803 was also
      examined. RESULTS: McAb PD4 could block tumor cell proliferation cycle and
      trigger cell death by inducing apoptosis, but expression of Fas antigen in MGC
      803 cells was negative. CONCLUSION: P40 is a tumor associated antigen which is
      distinct from Fas antigen. Molecular cloning of P40 will clarify the pathway and
      mechanism of apoptosis induced by this monoclonal antibody.

PMID- 10921054
TI  - [Comparative studies of the pharmacokinetics of 131I-3H11 after different routes
      of administration].
AB  - OBJECTIVE: To study the pharmacokinetics of 131I-3H11, a mAb to gastric cancer,
      by different routes of administration. METHODS: Three groups of rabbits were
      injected with 131I-3H11 through ear vein(i.v.), portal vein(pv) and into the
      peritoneal cavity(i.p.), respectively. At various time intervals, blood samples
      from the ear vein and portal vein, and the peritoneal fluid were collected and
      their radioactivities determined. RESULTS: (1) The radioactivity of ear vein
      blood and portal vein blood was the same in the i.v. group. In the peritoneal
      cavity, it was 1/3 of that in the blood. (2) In pv group, radioactivity of the
      portal vein blood was higher than that of the ear vein blood, but the difference
      became insignificant 30 min later. In the peritoneal cavity, it was 1/3 of that
      in the blood. (3) In i.p. group, radioactivity in the peritoneal cavity was
      highest, its peak activity was 37.2-fold and 5.4-fold as high as that of the
      venous blood, respectively. That in the portal vein blood was 6.9 times higher
      than in the ear vein blood. CONCLUSION: There is a significant pharmacokinetic
      advantage for i.p. over i.v. and pv routes of administration for the prevention
      and treatment of peritoneal recurrence and liver metastsis of gastrointestinal
      cancers after surgical resection.

PMID- 10921053
TI  - [Experimental study of the effect of angiogenesis inhibitor TNP-470 on the growth
      and metastasis of gastric cancer in vivo].
AB  - OBJECTIVE: To study the effect of angiogenesis inhibitor TNP-470 on the growth
      and metastasis of gastric cancer in vivo. METHODS: Metastatic model simulating
      human gastric cancer was established by orthotopic implantation of histologically
      intact human tumor tissue into gastric wall of nude mice. TNP-470 was
      administered s.c. at doses of 0 mg/kg, 15 mg/kg, 30 mg/kg, 60 mg/kg every other
      day for eight weeks. Ten weeks after implantation, the mice were sacrificed and
      the tumor size measured and the presence of metastasis recorded. The
      microvascular density was examined by immunohistochemical staining with anti
      human factor VIII antibody. RESULTS: Compared to the untreated controls, growth
      of the orthotopically implanted tumor was significantly reduced in size in mice
      treated with TNP-470 with an inhibition rate of 59.9%, 77. 0% and 84.9% at the
      dosage of 15 mg/kg, 30 mg/kg and 60 mg/kg, respectively. Tumor metastasis to the
      liver and peritoneaum was also significantly inhibited in a dose-dependent
      manner. The microvascular density was also decreased significantly in the treated
      mice. CONCLUSION: Angiogenesis inhibitor TNP-470 has strong inhibitory effect
      both on tumor growth and metastasis of human gastric cancer in nude mice.

PMID- 10921055
TI  - [Molecular biological evidence for the genetic stability of in vivo passaged
      doxorubicin resistant cell line S-180R].
AB  - OBJECTIVE: To assess the genetic stability of doxorubicin resistant sarcoma 180
      cell line(S-180R) after in vivo passages. METHODS: Flow cytometry, Southern blot,
      Northern blot and RT-PCR were used to examine genes and molecules related to drug
      resistance. RESULTS: The drug-efflux of S-180R was nearly 100-fold as high as
      that of the parental cells. The ratio of half peak width to peak height was 0.23
      as compared to 0.56 measured two years before when the S-180R cell line was
      initially established. The mdr-1 gene was significantly amplified and transcribed
      while the transcription of topoisomerase II alpha gene was decreased. However
      there was no increase in mRNA expression of the multidrug resistance associated
      protein(MRP). CONCLUSION: Compared with the initially established S-180R, its
      resistance to doxorubicin is not only maintained but in fact has been increased
      since in vivo passage for 2 years. The major mechanism is amplification and over
      expression of mdr-1 gene, but decreased topoisomerase II alpha also contributes.
      S-180R is an ideal experimental model for the study of doxorubicin resistance and
      its reversion.

PMID- 10921056
TI  - [Preoperative radiotherapy reduces cervical metastasis of supraglottic carcinoma:
      a prospective randomized trial in 201 patients].
AB  - OBJECTIVE: To evaluate the effectiveness of preoperative radiotherapy in the
      control of overall cervical lymph node metastasis from supraglottic carcinoma.
      METHODS: A prospective randomized study on 210 patients with supraglottic
      carcinoma was performed. Nine patients were lost from follow-up and therefore
      excluded. The analysis was based on the remained 201 patients including fifteen
      who did not complete the treatment protocol. Surgery alone(S) was carried out in
      102 patients and radiotherapy(40 Gy) followed by surgery (R + S) in 99 patients.
      All the patients were followed up for more than three years. RESULTS: No
      statistically significant difference in survival rates between S and R + S groups
      was found by using the Kaplan-Meier analysis. However, relative risk of overall
      cervical recurrence had a trend of reduction for patients in R + S group, versus
      patients in S group. There was a statistically significant reduction of lymph
      node metastasis in R + S group compared to S group in stage I-III(P = 0.0198)
      while in stage IV no such difference was observed. Patients with stage I-III
      disease who did not receive preoperative radiation were 1.766 times more likely
      to develop neck recurrence compared to patients who did. Among all the factors,
      only TNM stage and histological nodal status were found to be independent risk
      factors for regional control. Contralateral neck failure occurred more frequently
      in patients with advanced lesion(P = 0.020) and in patients without preoperative
      radiation(P = 0.018). CONCLUSION: There may be a trend towards improved control
      of cervical lymph node metastasis with preoperative radiation of 40 Gy dose in
      patients with supraglottic cancer in stage I-III of the disease.

PMID- 10921057
TI  - [Transglottic carcinoma and transglottic invasion of laryngeal carcinoma].
AB  - OBJECTIVE: To explore the definition of transglottic carcinoma and its
      pathological characteristics of local invasion, and to determine the distinction
      between transglottic carcinoma and transglottic invasion of laryngeal carcinoma.
      METHODS: Fifty total laryngectomy specimens of transglottic carcinoma were
      subject to whole-organ serial section, HE staining and microscopic observation.
      RESULTS: The ventricles of 50 cases were all invaded, the main lesion of
      carcinoma was in the ventricle, or the ventricle was the center of the lesion.
      The rate of invasion to paraglottic space(PGS) was 82%(41/50). Submucosal
      invasion was seen in 52%(26/50) and that with superficial mucosal invasion was
      seen in 38%(19/50). Superficial mucosal invasion rate was 10%(5/50). Deep
      submucosal invasion was the major way of tumor spread in transglottic carcinoma
      which equally involved the supraglottic and glottic regions. CONCLUSION:
      Transglottic carcinoma originates from the center of ventricle where it spreads
      to transglottic region. Submucosal extension is characteristic of local invasion.
      There are fundamental differences between transglottic carcinoma and transglottic
      invasion of laryngeal carcinoma in the late stage of the lesion.

PMID- 10921058
TI  - [Cervical lymph node metastasis: CT, ultrasound versus physical palpation].
AB  - OBJECTIVE: To evaluate the accuracy of CT, ultrasonography and manual palpation
      in the diagnosis of cervical lymph node metastasis and to identify the value of
      CT and ultrasound in the diagnosis of occult cervical lymph node metastasis.
      METHODS: Sixty patients (74 sides) were studied double-blindedly by CT and
      ultrasonography prior to cervical lymphadenectomy, and the results were
      correlated with histo-pathologic findings. RESULTS: According to histologic
      examination of the dissected specimens, in 56 of 74 sides there were cervical
      lymph node metastases, 46 of the 56 sides with metastatic nodes were diagnosed by
      manual palpation(sensitivity, 82.1%; specificity, 83.3%; accuracy, 82.4%).
      However, lymphnode metastases in 53 sides were revealed by CT(sensitivity, 94.6%;
      specificity, 94.4%; accuracy, 94.6%), i.e., CT discovered 70% of the occult
      metastatic nodes in this series. Lymph node metastases were diagnosed accurately
      in 51 sides by ultrasonography (sensitivity, 91.1%; specificity, 94.4%; accuracy,
      91.9%), and 50% of the occult metastatic nodes were found by ultrasound.
      CONCLUSION: CT, ultrasound examinations are superior to physical palpation in
      ascertaining cervical lymph node metastasis, as 50%-70% of the occult cervical
      metastatic nodes can be diagnosed.

PMID- 10921059
TI  - [Grouping of thoracic lymph nodes on CT scan according to American Thoracic
      Society classification].
AB  - OBJECTIVE: To assess the usefulness of the classification developed by the
      American Thracic Society (ATS) in the grouping of thoracic lymph nodes on CT
      scan. METHODS: Ten patients suffered from lymphoma (5 cases), sarcoidosis (2
      cases) and metastatic lymphadenopathy (3 cases) were examinated with CT. The
      intrathoracic lymph nodes were grouped according to the ATS nodal classification.
      RESULTS: Six areas were divided on the CT scans: (1) between the upper margin of
      the sixth cervical vertebra and the pulmonary apex, including nodes in group
      1R/L; (2) between the pulmonary apex and the upper margin of the aortic arch,
      including nodes in group 2R/L and 6; (3) between the upper margin of aortic arch
      and the carina, including nodes in group 4R/L, 5, 6 and 10R; (4) within 3 cm
      below carina, including nodes in group 7 and 10R/L; (5) between 3 cm from
      subcarina and the top of diaphragm, including nodes in group 8R/L and 14R/L; (6)
      intrapulmonary area, distal to the upper lobe bronchi, including nodes in group
      11R/L. CONCLUSION: The division of lymph nodes into six areas on CT scan makes
      the ATS lymph node classification more easily applicable.

PMID- 10921060
TI  - [Extent and mode of metastatic spread to lymph nodes in patients with
      adenocarcinoma of the gastric cardia: a multivariate analysis using COX
      proportion hazard model].
AB  - OBJECTIVE: To investigate lymph node metastases (LNM) and assess LNM level
      accurately after standard resection. METHODS: An analysis was done in 736
      patients with resected gastric cardia cancer whose postoperative survival time
      was longer than three months, through comparison of prognosis, frequency of LNM
      and ratio of the number of invaded to removed lymph nodes (I/R), using COX
      multivariate analysis model. RESULTS: (1) The most important prognostic variables
      were I/R, left gastric artery LNM, lesser curvature LNM, and paracardia LNM. (2)
      The patients without LNM had better survival (P < 0.001). (3) There were a
      relatively regular way of LNM and significant difference between LNM of single
      site and that of multiple sites on the frequency of LNM and I/R, respectively (P
      < 0.05). (4) There was significantly different I/R among group 1 (single
      paracardia LNM and single lesser curvature LNM), group 2 (single left gastric
      artery LNM and paracardia plus lesser curvature LNM) and group 3 (multiple sites
      in association with left gastric artery LNM) (P < 0.05). CONCLUSION: The
      dissemination of LNM seems to be as follows: from paracardia lymph nodes to
      distant lymph nodes, and from a single lymph node of one site to multiple sites
      with many lymph notes involved. It is suggested that group 1 LNM belongs to
      station 1, group 2 LNM to station 2 and group 3 LNM to station 3 according to
      their I/R.

PMID- 10921061
TI  - [Urokinase-type plasminogen activator (uPA), uPA receptor (uPA-R) and inhibitors
      (PA I -1) expression in hepatocellular carcinoma in relation to cancer
      invasion/metastasis and prognosis].
AB  - OBJECTIVE: To study the relevance of uPA, uPA-R and PA I -1 to hepatocellular
      cancer (HCC). METHODS: The expression at protein level for uPA, uPA-R and PA I -1
      was examined in 48 cases of HCC and 12 cases of benign tumors of the liver (as
      control) immunohistochemically. RESULTS: When compared to HCC-adjacent normal
      liver tissue and the control, positive rates of immune staining for uPA, uPA-R
      and PA I -1 on cell membrane were significantly higher in HCC cells (P < 0.05).
      Positive staining of uPA and uPA-R was seen in 16 of 22 and 19 of 22 cases of HCC
      with invasion, respectively (P < 0.01 and < 0.001). In 8 of 8 cases with cancer
      emboli, and in 6 of 6 cases with lymph node metastasis was the expression of uPA
      R positive. Compared with 2 of 17 cases without recurrence, uPA-R was positive in
      15 of 17 recurrent cases (P < 0.01). In 36 cases who survived, 17 was positive
      for uPA-R and 15 for PA I -1, while in 12 cases who died 2 years after surgery,
      12 and 9 cases were positive for uPA-R and PA I -1, respectively (P < 0.01 and <
      0.05). In 15 cases positive for all three parameters, 11 had cancer invasion and
      7 died in 2 years, while in the controls with negative staining 2 had invasion
      and none died in 2 years (P < 0.05). CONCLUSION: Expression of uPA, uPA-R and PA
      I -1 is increased in HCC, and uPA and uPA-R may contribute significantly to HCC
      invasion and metastasis. uPA-R and PA I -1 are associated with poor prognosis.

PMID- 10921062
TI  - [Navelbine plus cisplatin combination therapy in the treatment of advanced non
      small cell lung cancer: a report of 42 cases].
AB  - OBJECTIVE: To evaluate the results of combination chemotheray with navelbine
      (NVB) plus cisplatin (DDP) in the treatment of non-small cell lung cancer
      (NSCLC). METHODS: From 1992 through 1996, 42 patients with advanced NSCLC were
      enrolled in this study. The median age of the patients was 57 years.
      Adenocarcinoma was the most common type of malignancy. Seventeen patients had
      stage IIIB disease and 25 had stage IV. Twenty-four patients had no prior
      chemotherapy and 18 received previous chemotherapy. RESULTS: Partial response was
      observed in 20 patients with an overall response rate of 47.6%. The response
      appeared to correlate with dose intensity, as 54.2% response rate was achieved
      with a dose of NVB > or = 25 mg/m2/wk versus 38.9% response rate with NVB < 25
      mg/m2/wk. The median response duration was 3.3 months and the median survival
      period was 8.5 months. The dose limiting toxicity was neutropenia which was seen
      in all treated cases (66.6% in grades III and IV). The local venous toxicity was
      observed in 40.5% of the patients. CONCLUSION: A high response rate was obtained
      in advanced NSCLC treated by NVB plus DDP. NVB is a promising antitumor agent
      with tolerable toxicity.

PMID- 10921063
TI  - [The role of recombinant interferon alpha-2b in the treatment of advanced
      malignancies].
AB  - OBJECTIVE: To identify the efficacy and toxicity of recombinant interferon alpha
      2b in the treatment of advanced malignancis. METHODS: Interferon alpha-2b was
      administered intra-muscularly, the escalating dosage being 3 x 10(6) IU, twice in
      the first week, 6 x 10(6) IU twice in the second week and thereafter 9 x 10(6) IU
      twice weekly until the 8th week. RESULTS: Among 102 patients, 90 were eva luable.
      The overall response rate (RR) was 16.7%. The RR in patients with renal cell
      careinoma was 10.8% (4/37, with 2 complete and 2 partial responses), that in
      patients with malignant melanoma was 14.3% (4/28, 4 partial responses), it was
      50% (4/8, 4 partial responses) in malignant lymphoma and 20% (3/15, 3 partial
      responses) in breast cancer. The median response duration was 40 months in the
      patients with complete response, while only 4.8 months in patients with partial
      response. The major adverse reactions were flu-like syndrome, while gastro
      intestinal reactions and bone marrow suppression were mild. CONCLUSION:
      Recombinant interferon alpha-2b has antitumor activity in patients with advanced
      renal cell carcinoma, malignant melanoma and malignant lymphoma. It could be
      considered as a second line treatment regimen.

PMID- 10921064
TI  - [Ovarian metastasis from endometrial carcinoma: a report of 22 cases].
AB  - OBJECTIVE: To study the clinical characteristics of ovarian metastasis from
      endometrial carcinoma and its relation to pathologic features and prognosis.
      METHODS: Twenty-two cases of histologically confirmed ovarian metastasis from
      endometrial carcinoma were retrospectively reviewed. Prognostic factors such as
      clinical staging, grade, myometrial infiltration, recurrence and treatment
      methods were analyzed. RESULTS: The median age of this series was 50.6. Incidence
      of ovarian metastasis accounted for 4.4% in the same period. Ten out of 22 cases
      were in clinical stage I, 6 in stage II, and 6 in stage III. The treatment of
      choice was operation combined with radiotherapy. The overal 5- and 10-year
      survival rate was 61.5 and 55.9%, respectively. CONCLUSION: Ovarian metastasis
      from endometrial carcinoma is associated with poor prognosis. Aggressive
      treatment after operation is required. For young patients in early stage of the
      disease, circumscript attitude should be taken as to preserve the ovary or not.

PMID- 10921065
TI  - [Proliferating cell nuclear antigen (PCNA) in ovarian carcinoma and its relation
      to lymph node metastasis and prognosis].
AB  - OBJECTIVE: To investigate expression of proliferating cell nuclear antigen (PCNA)
      in ovarian epithelial cancer and its relation to lymph node metastasis, second
      look laparotomy (SLL) and prognosis. METHODS: Monoclonal antibody PC10 was used
      to stain PCNA in archival paraffin-embedded tissues. RESULTS: PC10 immunostaining
      was performed successfully in all 74 primary and 31 intraperitoneal metastatic
      tumors. The expression of PCNA was significantly elevated in 31 metastatic tumors
      compared with their primary tumor from the same patient (7.94 vs 6.89, P =
      0.042). The expression was more marked in bilateral than in unilateral ovarian
      cancer but it was not associated with lymph node metastasis, clinical stage,
      histologic grade and subtype. In 28 patients with stage III ovarian cancer
      undergone SLL, the mean immunoreactive score (IRS) of PCNA of the primary tumor
      was significantly higher in patients with negative SLL than in those with
      positive SLL (7.59 vs 6.10, P = 0.03). Since chemotherapy was performed following
      surgical debulking, negative SLL more frequently seen in patients with high PCNA
      expression might suggest better chemotherapeutic sensitivity due to higher
      proliferation fraction of tumor cells. Univariate analysis of survival indicated
      that the overall survival was inversely associated with the level of PCNA
      expression, while multivariate analysis with Cox's model showed that independent
      prognostic factors were the residual tumor after primary debulking (P < 0.001)
      and clinical stage (P < 0.05), followed by PCNA expression (P = 0.09).
      CONCLUSION: The expression of PCNA may be useful in predicting prognosis, but is
      not correlated with lymph node metastasis.

PMID- 10921066
TI  - [Clinico-pathologic study of Ewing's sarcomas of bone and soft tissue and
      peripheral primitive neuroectodermal tumors].
AB  - OBJECTIVE: To study the diagnosis and differentiation of EW and PNET. METHODS:
      Fourteen cases of Ewing's sarcomas (EW) and peripheral primitive neuroectodermal
      tumors (PNET) were studied by light microscopy, immunohistochemistry and electron
      microscopy (EM). Twelve cases were followed up. Schmidt criterion was used for
      the differential diagnosis of EW and PNET. RESULTS: There were 6 cases of EW and
      8 cases of PNET. Six of 8 PNET cases had Homer-Wright (H-W) rosettes. In this
      series, 12/14 cases were positive for O13 (HBA71) staining. NSE was positive in 3
      cases of EW. All PNET cases were positive for neural markers, and 5 of them were
      positive for more than two of these markers. Electronmicroscopically, there were
      neurosecretory granules (4/4 cases), nerve-like protrusions and microfilaments
      (1/4 case) in PNET. In 3 of 6 EW and 1 of 6 PNET, PAS staining was positive.
      During the follow-up period from 2 months to 5 years, 3 cases with intraosseous
      EW remain alive and free of tumor. The remaining patients are dead or having
      their tumors metastasized. CONCLUSION: EW is more primitive in cell
      differentiation, while PNET has more neural differentiation. The presence of H-W
      rosettes is an important morphologic feature of PNET. To differentiate EW from
      PNET is of clinical significance O13 is a useful marker for the diagnosis of
      EW/PNET.

PMID- 10921067
TI  - [Comparison of prognosis between inguinal cryptorchic seminoma and scrotal
      seminoma].
AB  - OBJECTIVE: To analyse the prognosis of patients with inguinal cryptorchic
      seminoma. METHODS: From 1985 through 1991, 43 patients with inguinal seminoma of
      undescended testis were treated and the therapeutic effect retrospectively
      reviewed. There were 33 patients in stage I, 8 in stage II, 1 in stage III, and 1
      in stage IV. All patients had inguinal orchiectomy. Patients in stage I and II
      were primarily treated with radiotherapy, whereas one patient in stage III and
      another in stage IV were treated with radiotherapy or chemotherapy. RESULTS: The
      5- and 10-year overall survival was 93.0% and 90.3%, respectively. The
      corresponding disease-free survival was 88.1% and 85.3%, respectively. The
      overall 5- and 10-year survival by stage was 100% and 100% for stage I, 75.0% and
      60.0% for stage II, respectively. Two patients relapsed and were successfully
      treated with radiotherapy. CONCLUSION: Prognosis for inguinal cryptorchic
      seminoma is as good as that of scrotal testicular seminoma. Postorchiectomy
      radiotherapy encompassing para-aortic and ipsilateral iliac nodes is effective
      for stage I and early stage II inguinal crytorchic seminoma. The inguinal nodes
      should be included in the treatment ports only when they are involved or if there
      is obvious involvement of surrounding tissues by the primary tumor.

PMID- 10921068
TI  - [Feasibility study of laser-induced fluorescence (LIF) spectrum for diagnosis of
      colon cancer].
AB  - OBJECTIVE: To study the usefulness of laser-induced fluorescence (LIF) spectrum
      for diagnosis of colon cancer. METHODS: Nitrogen laser, wavelength 337 nm,
      optical multichannel analyzer (OMA III) were used to demonstrate LIF spectra. A
      standard spectrum of LIF of colon cancer was used to analyse that of 51
      surgically removed colon specimens and the results were compared with
      pathological findings. RESULTS: Compared with pathological findings, LIF spectrum
      examination had 80.0% sensitivity, 100% specificity, with positive predictive
      value of 100%, negative predictive value of 83.9% and accuracy of 90.2% for the
      diagnosis of colon cancer, respectively. CONCLUSION: Laser-induced fluorescence
      (LIF) spectrum of colon is of use in the diagnosis of colon cancer.

PMID- 10921069
TI  - [Reminiscence of 44 year research life].

PMID- 10921070
TI  - [Inverse agonist: a novel discovery in receptor research].
AB  - There is a part of unligated receptors in a state of activity (R*). The active
      (R*) and inactive (R) receptors exist in equilibrium. Some antagonists have a
      higher affinity with R as compared with R*, resulting in a decrease in the
      proportion of R* in the equilibrium, and inducing a biological response opposite
      to those of agonist. These antagonists are termed inverse agonists. In some
      diseases caused by receptor mutation or over expression, the therapeatic benefits
      of inverse agonist encourage further exploration.

PMID- 10921071
TI  - [Direct modulatory effects of G proteins on voltage-dependent ion channels of
      nerve cells].
AB  - Neurotransmitters have regulative effects on voltage-dependent ion channels of
      nerve cells. Recent studies have shown that voltage-dependent channels were
      modulated by transmitters through direct interactions between G proteins and
      channels without any known second messengers being involved. This gave us a novel
      understanding of the relations between G proteins and voltage-dependent ion
      channels. This article reviews the phenomena, characteristics, and mechanisms
      about voltage-dependent channels modulated by transmitters through direct effects
      of G proteins.

PMID- 10921072
TI  - [Method of mRNA differential display and its application in life science].
AB  - The changes of mRNA expression level control cell function. Many factors such as
      individual development, cell proliferation and differentiation, and even
      apoptosis, physiological stimuli, and drug treatment will change the level of
      gene expression. Comparisons of gene expression in different cell types provide
      the underlying information for analyzing the molecular and cellular mechanisms of
      the physiological processes. A method of mRNA differential display is developed
      recently, providing a powerful and useful tool, which can efficiently and rapidly
      isolate the genes that display a difference in transcription. These genes may
      play important role in cell function.

PMID- 10921073
TI  - [LIM homeobox genes family in nervous system].
AB  - Homeobox genes define a class of genes containing homeobox sequences and encoding
      proteins, that are identified as transcription regulator controlling cellular
      development and differentiation, and controlling patterns of gene expression. LIM
      homeobox genes contain both a homeobox and a conservative sequences (encoded LIM
      domain). The members of the LIM homeobox genes family which have recently been
      identified include lin-11, mec-3, apterous(ap), isl-1, LH-2, Rlim, lim-1, lmx-1,
      Xlim-1 and Xlim-3. Recent findings suggested that products expressed by LIM
      homeobox genes family play an important role in adjusting differentiation and
      developmental of the organism. The effects of LIM homeobox genes in the
      differentiation and development of neurons are currently attracting more and more
      attention.

PMID- 10921074
TI  - [The discovery of pituitary adenylate cyclase activating polypeptide (PACAP) and
      its research progress].
AB  - Pituitary adenylate cyclase activating polypeptide(PACAP) is a new bioactive
      polypeptide originally isolated from ovine hypothalamus. It is widely distributed
      in the central and peripheral nervous systems, and some non-nervous tissues as
      well. Mediated by PACAP receptors, it stimulates adenylate cyclase and
      subsequently increases the cAMP level in target cells. PACAP is not only a new
      type of hypophysiotropic hormone, but also functions as a neurotransmitter and
      neuromodulator. In addition, it plays a role in paracrine and autocrine
      regulation of certain types of cells.

PMID- 10921075
TI  - [Study of the molecular mechanism of human cytochrome P450 and genetic
      polymorphism of drug oxidative metabolizing enzyme].
AB  - Polymorphism has been detected in a variety of drug-metabolizing enzymes at both
      phenotypic and genotypic level. Human cytochrome P450 enzymes have been studied
      extensively in recent years, and the majority of mutations which give rise to a
      defective phenotype have now been identified(for example CYP2D6, CYP2C19, etc.).
      There are some groups of enzymes showing definite polymorphism at the phenotypic
      level but the exact genetic mechanisms are not yet clear(CYP1A1, CYP1A2, etc.).
      There are still other groups of enzymes, showing some indication of polymorphism
      at either the phenotypic or genotypic level yet have not been unambiguously
      demonstrated (for example CYP2A6, CYP2C9, CYP2E1, CYP3A4, etc.). The molecular
      mechanism of all these polymorphisms and possible polymorphisms is discussed,
      with particular reference to the effects of this variation on drug metabolism and
      on the susceptibility to chemically-induced diseases.

PMID- 10921076
TI  - [Regulation of the central opioidergic nervous system on the emotional state of
      anxiety and its possible mechanisms].
AB  - The spontaneous withdrawal from morphine in morphine-dependent rats significantly
      decreased the duration of active interaction in social interaction test and the
      number of licks during the shock-punished period in Vogel's conflict procedure,
      which were attenuated by buspirone, a 5-HT1A agonist, as well as para
      chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Naltrexone
      (NTX), a potent opioid receptor antagonist, also dose- and time-dependently
      reduced both indices mentioned above, which was blocked by morphine or PCPA and
      was enhanced by 5-hydroxytryptophan, a precursor of 5-HT. In the test of
      neurotransmitter releases in rat brain slices, both morphine-withdrawal and NTX
      enhanced high potassium(30mM)-induced 5-HT release in slices of the area of the
      raphe nucleus. These results suggested that both morphine-withdrawal and NTX
      produced anxieties in morphine-dependent and normal rats, respectively, which
      were mediated by the central 5-HTergic neurotransmission. Central opioidergic
      neurons inhibited 5-HTergic neurons tonically and presynaptically. Such an effect
      was reduced or blocked by NTX, or during morphine-withdrawal, and 5-HTergic
      neurons were disinhibited, leading to a state of anxiety.

PMID- 10921077
TI  - [Effects of dynorphin A1-17 on the activities, immunoreactivities and mRNA
      expression of cNOS and iNOS in rat spinal cord and their mechanisms].
AB  - Intrathecal administration(i.t.) of Dynorphin A1-17(Dyn) 1.25-20 nmol produced
      dose-dependent paralysis of hindlimbs and tail as well as inhibition of tail
      flick and foot flinch reflexes. The Dyn spinal neurotoxicity and antinociception
      involve two differential mechanisms: Enhancement of NMDA-Ca(2+)-NOS/NO pathway
      and c-fos over-expression in the ventral spinal cord for neurotoxicity, and
      depression of NMDA receptor and NOS activities in the dorsal spinal cord for
      antinociception. Both brain-derived constitutive NOS (predominant at early stage)
      and inducible NOS (at later stage) are detrimental, but endothelial constitutive
      NOS might be beneficial to Dyn spinal neurotoxicity. Dyn exerts a dualistic
      modulatory effect on [Ca2+]i of the cultured rat single spinal neurons, inducing
      sustained overload of intracellular free calcium via both NMDA and kappa receptor
      activation at higher concentrations, and producing significant inhibition of the
      depolarization-evoked calcium influx only via kappa receptor activation at lower
      concentrations. Dyn exposure for 1 h produced direct neurotoxicity in the
      cultured spinal neurons within an optimal range of concentrations.

PMID- 10921078
TI  - [Recent progress in the use of immediate early genes in neuroscience].

PMID- 10921079
TI  - [C-fos expression and research on brain mechanisms of psychological stress].

PMID- 10921080
TI  - [Discovery of dynamin and the mechanism of vesicle recirculation in nerve
      terminal].

PMID- 10921081
TI  - [MPTP-treated old rat is an appropriate animal model for parkinsonism study].

PMID- 10921082
TI  - [Ca2+/calmodulin-dependent protein kinase II and its functions].

PMID- 10921083
TI  - [Angiotensin receptors and their signal transduction].

PMID- 10921084
TI  - [Mammalian DNA methylase].

PMID- 10921085
TI  - [Mitochondrial encephalomyopathies and mitochondrial DNA].

PMID- 10921086
TI  - [Visual physiological mechanisms of illusory contours perception].

PMID- 10921087
TI  - [Melatonin and aging].

PMID- 10921088
TI  - [Iso-prostanes and their significance].

PMID- 10921089
TI  - [Advance in the research of P-type calcium channel].

PMID- 10921090
TI  - [Progress in platelet-activating factor receptor research].

PMID- 10921092
TI  - [Retrospective analysis of 417 cases of acute leukemias in the elderly in
      Shanghai. Shanghai Leukemia Cooperative Group (SLCG)].
AB  - OBJECTIVE: To investigate the characteristics of acute leukemia (AL) in the
      elderly in Shanghai. METHODS: Four hundred and seventeen elderly ALs registered
      in SLCG between 1984 and 1994 were retrospectively analyzed. RESULTS AND
      CONCLUSION: Elderly AL accounted for 14.5% of all AL, AML was the major type, and
      M5 and L3 were the commonest subtypes. Complete remission rate of elderly AL was
      23.9%, which was lower than that of young adults'(53.7%). Routine dose induction
      chemotherapy was more effective than low dose chemotherapy. Multivariate analysis
      showed that the risk factors for early death were age > or = 70, hemoglobin < 40
      g/L, bone marrow blast cell > 80%, DIC presentation, secondary to MDS, or other
      conditions such as heart or pulmonary diseases.

PMID- 10921093
TI  - [Clinical study of childhood acute myelogenous leukemia].
AB  - OBJECTIVE: To investigate the clinical characteristics, treatment responsiveness
      and prognostic factors of childhood acute myelogenous leukemia. METHODS: Two
      hundred and seventy-four children with acute myelogenous leukemia diagnosed
      between 1978 and 1995 were retrospectively analyzed. RESULTS AND CONCLUSIONS:
      Male:female is 1.6:1. The median age was 7.25 years. M2 and M3 were the commonest
      subtypes(80%). Twenty cases were hyperleukocytosis and 24 with extramedullary
      involvement. Thirty two percent of the patients was Auer rods positive. Two
      hundred and forty-four patients received combination chemotherapy. Complete
      remission (CR) rates varied from 55.88% to 92.31%. Intensive
      chemotherapy(including DA, DA + Vm26 or Vp16) was the cornerstone for high CR
      rate. Other factors influencing CR rate were initial WBC count and
      hepatosplenomegaly.

PMID- 10921091
TI  - [The role of plasminogen activators and their inhibitors in the nervous system].

PMID- 10921094
TI  - [The structure and mRNA expression of p16 gene in AML cells].
AB  - OBJECTIVE: To explore the role of p16 gene in the pathogenesis of AML. METHODS:
      PCR-SSCP and Northern blot were used to analyse the structure and mRNA expression
      of p16 gene in 16 cases of AML. RESULTS: No deletion or mutation of p16 gene were
      found in all of the 16 cases. The p16 mRNA expression in 12 AML at diagnosis or
      relapse was significantly lower than that in 4 long term remission cases and
      normal controls. p16 mRNA expression was significantly higher in a case of AML
      with p53 mutation. CONCLUSION: p16 gene may not play an important role in the
      pathogenesis of AML. The high p16 expression in the patient with p53 mutation
      might reflect a kind of inbalance of the feedback cycle.

PMID- 10921095
TI  - [Study on expression of IRF-1 gene in human leukemia with RT-PCR and the silver
      sequence techniques].
AB  - OBJECTIVE: To explore preliminarily the changes of IRF-1 gene expression in
      leukemias. METHODS: The expression of IRF-1 gene in 24 leukemia patients and 3
      leukemic cell lines were studied with RT-PCR and the silver sequence techniques.
      RESULTS: No expression of IRF-1 gene in 3 patients, and significantly decreased
      expressions in 5 patients and in HL-60 and HIMeg cell lines were revealed.
      CONCLUSION: The mechanism of human leukemogenesis may be partly associated with
      no or low-expression of IRF-1 gene.

PMID- 10921096
TI  - [Expression of Wilms' tumor gene (WT1) in leukemias and its clinical
      implication].
AB  - OBJECTIVE: To elucidate the expression of Wilms' tumor gene (WT1) in leukemias
      and its clinical implication. METHODS: Expression of WT1 mRNA was detected in
      four leukemia cell lines, 25 AML patients, 11 ALL patients, 9 CML patients, 15
      healthy subjects and 10 non-blood diseases patients by using RT-PCR. RESULTS: WT1
      mRNA expression was revealed in K562, HL-60 and TF-1 cell lines, 21 of 25 (84%)
      AML patients, 8 of 11 (73%) ALL patients, 2 CML patients in blast crisis and 1 of
      7 CML patients in accelerated and chronic phase. WT1 mRNA was undetectable in
      PBMNC from 15 healthy subjects and in bone marrow cells from 10 non-blood
      diseases patients. CONCLUSION: WT1 gene is expressed in the majority of acute
      leukemias and thus is involved in human leukemogenesis. WT1 is also a new
      important marker for monitoring MRD in acute leukemias.

PMID- 10921097
TI  - [Synergistic reversal effect of quinine in combination with modulators on
      multidrug resistant cell line K562/HHT].
AB  - OBJECTIVE: To develop effective combination of drug resistance modulators.
      METHODS: The reversal effects of quinine (Quin) in combination with cyclosporin A
      (CsA), dipyridamole (DPM) or tamoxifen (Tam), respectively on the drug resistance
      of K562/HHT were studied by MTT, flow cytometry and median-effect principle.
      RESULTS: The reversal effectiveness of the modulator combinations was 2-3 times
      as much as that of each modulator alone. Synergistic interaction between Quin and
      DPM or Tam was greater than that between Quin and CsA. Quin combined with CsA
      increased intracellular DNR accumulation significantly as compared with either of
      them alone. CONCLUSION: There was synergistic interactions between Quin and CSA,
      DPM or Tam, and combination of modulators with different operating mechanisms had
      a greater synergistic interaction.

PMID- 10921098
TI  - [Detection of CBF beta-MYH11 fusion transcript and inv(16)(p13;q22) in acute
      myelomonocytic leukemia(M4) by RT-PCR and FISH].
AB  - OBJECTIVE: To study the clinical significance of inv(16) and CBF beta-MYH11
      fusion gene in the diagnosis and prognosis for M4Eo. METHODS: CBF beta-MYH11
      fusion transcripts and inv (16) were analyzed by reverse-transcriptase polymerase
      chain reaction(RT-PCR) and fluorescence in situ hybridization(FISH),
      respectively, in acute myelomonocytic leukemia(M4) with or without eosinophilia.
      RESULTS: In fifteen cases tested, one case of M4Eo and one of 9 M4 without
      eosinophilia were found to have CBF beta-MYH11 fusion transcript. Follow-up of
      the M4Eo patient showed residual PCR positivity 2 months after complete
      remission. CONCLUSION: The data suggest that screening by both RT-PCR and FISH
      should be performed in all AML-M4 regardless of morphologic features to allow
      accurate diagnosis and prognosis of M4 patients.

PMID- 10921099
TI  - [The role of hematopoietic growth factors on extensive apoptosis of
      myelodysplastic hematopoietic cells and its clinical significance].
AB  - OBJECTIVE: To investigate the effects of hematopoietic growth factors (HGFs) on
      apoptosis of hematopoietic cells in myelodysplastic syndromes (MDS) patients.
      METHODS: CD34+ cells in bone marrow from 12 MDS patients were purified by an
      immunomagnetic beads sorting system. Apoptosis of hematopoietic precursors was
      assayed by propidium iodine staining and flow cytometric analysis. RESULTS AND
      CONCLUSION: High dose rhEpo partly suppressed apoptosis of hematopoietic cells in
      MDS patients. At the 7th, 10th, 14th, cultured day, the apoptotic percentages of
      the high dose Epo group (rhEpo 200 U/ml or 100 U/ml) were substantially lower
      than that of the low dose group (20 U/ml, 2 U/ml and 0.2 U/ml) and showed a dose
      dependent effect with rhEpo. rhGM-CSF and rhIL-3 could also suppress
      hematopoietic cell apoptosis in vitro, the differences between the high dose
      group (rhIL-3 200 U/ml or rhGM-CSF 500 U/ml) and the low dose group (rhIL-3 50
      U/ml or rhGM-CSF 50 U/ml) were significant. Extensive apoptosis of
      myelodysplastic hematopoietic cells were markely suppressed when rhEpo and rhIL-3
      or rhEpo and rhGM-CSF were given together.

PMID- 10921100
TI  - [Expression of WT1 gene in leukemia and its significance].

PMID- 10921101
TI  - [Research on the molecular etiology of inversion of chromosome 16 in the patients
      with acute myeloid leukemia].

PMID- 10921102
TI  - [Study on combined chemosensitivity test in acute non-lymphocytic leukemia].
AB  - OBJECTIVE: To explore the methods of combined chemosensitivity test in vitro.
      METHODS: The chemosensitivity of leukemia cells to 7 kinds of combined
      chemotherapy regimens, including DA, HA, AA, MA, HAD, HAA and HAM, was estimated
      in 79 patients with ANLL by MTT assay in vitro. The ratios of drug combinations
      at which synergistic interactions between drugs are to the highest levels were
      determined by using Chou's "median effect analysis". RESULTS: There were 67
      S(sensitive)/S, 9 R(resistant)/R, 2 R/S, 1 S/R(in vitro/in vivo) in 79 patients.
      The general, positive and negative coincident rates of in vitro with in vivo,
      specificity and sensitivity were 96.2%, 98.5%, 81.8%, 88.9% and 97.1%,
      respectively. CONCLUSION: This method is better than the single drug test, and it
      is more useful to find drug resistant patients.

PMID- 10921103
TI  - [The clinical significance of multidrug resistance associated protein(MRP) gene
      expression in acute leukemia].
AB  - OBJECTIVE: To investigate the relationship between the expression of the
      multidrug resistance-associated protein(MRP) gene and clinical drug resistance in
      acute leukemia(AL). METHODS: Semi-quantitative reverse transcriptase polymerase
      chain reaction was used to examine the expression of MRP gene in 65 bone marrow
      aspirates of AL patients and 15 normal volunteer's peripheral blood mononuclear
      cells. The expression level of MRP were expressed as ratio of MRP/beta 2M(beta 2
      microglobulin) and the ratio of MRP/beta 2M > or = 0.3 was defined as MRP
      positive. RESULTS: The level of MRP mRNA and the positive percentage of MRP in
      relapsed-refractory group were significantly higher than that in normal control
      group. In newly diagnosed group, the first complete remission rate of MRP
      negative patients(84%) was significantly higher than that of MRP positive(25%)
      patients. MRP expression level was different in leukemia sub-type. MRP and mdr-1
      genes were examined simultaneously in 65 AL patients, the mean expression level
      and positive percentage of MRP and mdr-1 in clinical resistance group were
      significantly higher than those in non-resistance group. No significant
      correlation was found between the MRP and mdr-1 expression(rs = 0.1683).
      CONCLUSION: High expression of MRP leads to drug resistance and it is an
      unfavorable factor to prognosis.

PMID- 10921104
TI  - [The correlation between p170, p26 and multidrug resistance in refractory/relapse
      acute leukemia].
AB  - OBJECTIVE: To explore the role of two membrane proteins, p170 and p26, in
      clinical drug resistance and their correlation. METHODS: The expression of p170
      and p26 in bone marrow cells from 39 acute leukemia patients were detected by
      flow cytometry. RESULTS: The expression ratios of p170 and p26 were 15.89% +/-
      4.41% and 17.32% +/- 10.20%, respectively, in previously untreated group, and
      31.02% +/- 14.33% and 33.78% +/- 15.97%, respectively, in refractory/relapse
      group. The difference between the two groups was significant, while there were no
      correlation between p170 and p26 (r = -0.1578, P > 0.5). CONCLUSION: Both p170
      and p26 were related to clinical multidrug resistance, but the mechanisms were
      different.

PMID- 10921105
TI  - [Study on effects of new retinoids in combination with IFN-gamma on proliferation
      and differentiation of U937 cell and its mechanism].
AB  - OBJECTIVE: To illustrate the effects of new retinoids in combination with IFN
      gamma on the proliferation and differentiation of U937 cell and its mechanism.
      METHOD: Effects of new retinoids R9158, YS904012 in combination with IFN-gamma on
      the proliferation and differentiation of U937 cells were studied by detecting
      NBT, expression of CD14, CD68 and c-myc, and cell cycle shift. RESULT: When the
      U937 cells had been first treated with new retinoid for 24 hours, and then with
      IFN-gamma, the differentiation activity could be enhanced, the reverse of the use
      of two agent in chronology displayed much lower synergistical effect. Retinoids
      could down regulate c-myc expression and shift the cell population from S phase
      to G0/G1 phase within 24 hours, and the activity of YS904012 was greater than
      that of other retinoids. CONCLUSION: New retinoids in combination with IFN-gamma
      synergistically induced U937 differentiation. Retinoids may play an important
      role in triggering the differentiation.

PMID- 10921106
TI  - [Ex vivo study of ultraviolet-B inactivating immunocompetence and hematopoietic
      potential of cord blood].
AB  - OBJECTIVE: To determine the differences of the effect of ultraviolet-B(UVB) on
      lymphocyte and hematopoietic progenitor cell in cord blood. METHODS: The
      viability, proliferative response and stimulatory activity in mixed lymphocyte
      culture (MLC), colony forming unit-granulo-monocyte (CFU-GM) colony growth and
      percentage of CD34+ cell of cord blood in Hanks medium after 0, 5, 10, 20, 50
      mJ/cm2 UVB-irradiation were compared. RESULTS: Like the proliferative response
      and stimulatory activity, CFU-GM colony also showed UVB-irradiation dose
      dependent decrease. However, much less colonies were destroyed by UVB irradition
      less than 10 mJ/cm2. More obvious differences were found when 20%(vol/vol) bovine
      serum was added to the MNC medium. The percentage of CD34+ cell remained
      unchanged after UVB exposure. CONCLUSION: A lower dose of UVB exposure can
      slectively inactivate cord blood lymphocyte and antigen presenting cell while
      sparing hematopoietic progenitor cells. The data indicates the possibility of
      utility of UVB irradiation for graft-versus-host disease prophylaxis in cord
      blood transplantation.

PMID- 10921107
TI  - [The effects of intraperitoneal injection of IL-2 recombinant adenovirus and/or
      IL-3 recombinant adenovirus on the hematological recovery of murine model
      receiving high dose chemotherapy].
AB  - OBJECTIVE: To investigate the effect of Ad-IL-2 and/or Ad-IL-3 on the
      hematological recovery of murine model receiving high dose chemotherapy. METHODS:
      Ad-IL-2 and/or Ad-IL-3 were i.p. injected into experimental mice after high dose
      cyclophosphamide(200 mg/kg). RT-PCR analysis of peritoneal cells and cytokine
      levels in murine serum were detected to confirm gene transfering. The number of
      peripheral WBC, femur MNC and CFU-GM in bone marrow were observed continuously.
      RESULTS: After i.p. injection of Ad-IL-2 and/or Ad-IL-3, the transfected IL-2 and
      IL-3 gene were identified by RT-PCR analysis of peritoneal cells, high level of
      IL-2 and/or IL-3 were detected in murine serum. After i.p. injection of AD-IL-3,
      the number of WBC, femur MNC and CFU-GM in bone marrow significantly increased,
      while i.p. injection of Ad-IL-2 had no effect on improving hematological
      recovery. And the effect of i.p. injection of both Ad-IL-2 and Ad-IL-3 was not
      significantly different from that of injection either of them. CONCLUSION: i.p.
      injection of Ad-IL-3 can increase hematological recovery after high dose
      chemotherapy.

PMID- 10921108
TI  - [The serum levels of soluble interleukin-2 receptor in patients with malignant
      lymphocytic proliferative disorders].
AB  - OBJECTIVE: To explore the changes of serum levels of soluble interleukin-2
      receptor (sIL-2R) in lymphocytic malignancies and its clinical implication.
      METHODS: The serum levels of sIL-2R were measured in 60 cases of patients with
      various malignant lymphocytic proliferative disorders by using ELISA method. At
      the same time, the ratio of CD4+/CD8+ of peripheral blood mononuclear cells was
      also determined in 43 patients by using fluorescence activated cell sorter(FACS).
      RESULTS: The serum levels of sIL-2R in patients with multiple myeloma(MM), non
      Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia(ALL) were significantly
      higher than that of normal value. The ratio of CD4+/CD8+ measured in 43 patients
      were markedly lower than that of normal value. In MM, NHL and ALL patients, the
      higher values of sIL-2R were revealed in severe cases or late stage of these
      diseases. The levels of sIL-2R were independant of the infection in these cases.
      CONCLUSION: sIL-2R levels significantly elevated as the disease progressing, and
      the immune function decreasing, and the sIL-2R level may be used as an effective
      clinical marker.

PMID- 10921109
TI  - [Measurement of five cytokines in the serum of malignant lymphoma patients].
AB  - OBJECTIVE: To study the clinical significance of serum cytokine levels in
      patients with malignant lymphoma(ML). METHODS: Serum levels of five cytokines and
      receptor were measured in 49 patients with ML by RIA and ELISA. RESULTS: Except
      TNF alpha, significantly higher pretreatment levels of interleukin-2(IL-2),
      soluble interleukin-2 receptor(sIL-2R), interleukin-6(IL-6) and interleukin-8(IL
      8) were observed in most of ML patients at diagnosis or relapse as compared with
      controls(P < 0.05). Cytokine levels declined in responding patients after therapy
      and there were no differences between CR cases and controls, the cytokine levels
      remained elevated in non-responding patients. The levels of IL-2 and sIL-2R
      correlated with the clinical stage, which were significantly higher in patients
      in stage III, IV. The increase of sIL-2R correlated with the tumor burden. The
      level of IL-6 was higher in patients presenting B symptoms and had no correlation
      with the clinical stage. The elevated IL-8 level correlated with the clinical
      stage and presenting B symptoms of ML patients and had no correlation with other
      clinical-hematological parameters. CONCLUSION: The changes of cytokines may be
      served as a means to observe the condition of ML patients and supervise their
      response to treatment.

PMID- 10921110
TI  - [Mechanism of IL-6 secretion in bone marrow cells from multiple myeloma
      patients].
AB  - OBJECTIVE: To explore the mechanism of interleukin-6(IL-6) secretion in bone
      marrow cells from patients with multiple myeloma(MM). METHODS: Expression of IL-6
      in bone marrow mononuclear cells(BMMNC) from MM patients(n = 16) and controls(n =
      19) was detected by using double labelled immunofluorescence. RESULTS: In MM
      group, the positive rates of IL-6 expression were 15.4% +/- 6.5% in BMMNC, 7.9%
      +/- 2.9% in myeloma cells, and 4.5% +/- 1.2% in stromal cells, while in controls
      the positive rates were 4.6% +/- 2.3% in BMMNC, 2.6% +/- 1.1% in stromal cells
      and 0.7% +/- 0.1% in plasma cells, respectively. The positive rates in MM group
      were all significantly higher than those in controls(P < 0.001). The cytoplasmic
      IgG+ and vWF+ cells percentages in BMMNC were also significantly higher in MM
      group than those in controls. CONCLUSION: Elevated IL-6 in MM patients was
      secreted by both myeloma cells and stromal cells, and the mechanism of both
      autocrine and paracrine may be involved in pathogeneses of multiple myeloma.

PMID- 10921111
TI  - [Specific types of myelodysplastic syndromes].

PMID- 10921112
TI  - [Advances of research on the action of purinergic drugs and hereditary
      polymorphism of thiopurine methyltransferase].

PMID- 10921113
TI  - [Study on the epidemiological characteristics and strategy of surveillance in low
      endemic areas of malaria in Hubei].
AB  - Due to good programs on case finding and control, malaria has decreased to a low
      level in China. Hence, the existing surveillance program of undertaking blood
      smear from cases with fever finds very few positives in the millions of
      examinees. Previously, all blood slides were collected from clinically diagnosed
      cases of malaria (group 1), suspected malaria cases (group 2), fever of unknown
      reasons (group 3) or common cold (group 4) in low or moderate malaria endemic
      areas in Hubei Province. In low prevalence areas, the positive rates on slides
      were 0.6/10,000 and 0.1/10,000 in group 3 and group 4 while 95.38% of the
      confirmed malaria cases were from those having clinical malaria or suspected
      malaria. It is suggested that group 3 and group 4 be dropped from low prevalence
      areas to encourage greater efficiency in case detection in the clinical and the
      suspected malaria groups.

PMID- 10921114
TI  - [Analysis of clincal poliomyelitis in Shandong Province from 1993-1996].
AB  - Wild poliovirus has not been isolated in Shandong province since Apr. 1991.
      However, 71 clinically polio cases were diagnosed by an expert group, including
      50 potential Vaccine Associated Paralytic Poliomyelitis (VAPP) including 31
      having the sabin strain in the stools, from 1993 to 1996. The overall frequency
      of VAPP was one case per 1.25 million doses distributed. The relative frequencies
      of first dose in the OPV series was one case per 218,800 doses vs one case per
      1.01 million for second dose. Based on data from the 31 cases, we estimated that
      the rates had been one case per 438,000 first dose and one case per 6.42 million
      second dose and one case per 10.44 million among the contacts of the cases. This
      results seemed to be higher than from other reports. Clinically confirmed
      poliomyelitis cases in Shandong were diagnosed by the experts group. The
      classification of clinical polio cases is important in the polio eradication
      program.

PMID- 10921115
TI  - [Geneotic analysis of wild type measles viruses circulating in China during 1995
      1997].
AB  - To investigate the molecular epidemiology of measles virus (MV) in China,
      sequence analysis of MV was performed based on a 282-nt region of the
      nucleoprotein (N) gene and a 450-nt region of heamaglutinin (H) gene by direct
      sequencing of RT-PCR amplicons obtained from clinical specimens. Results revealed
      that one MV strain belonged to ED-like genotype and remainder strains were
      clustered into a new genotype which was distinct from Chinese vaccine strains and
      MV strains circulating in other countries, as previously described representing a
      new genotype. There was up to 15.4% divergence in the nt-282 N gene and 10.8%
      divergence in the nt-450 H gene between the new genotype and other genotypes.

PMID- 10921116
TI  - [Infection of GBV-C virus among hepatitis and HCC patients].
AB  - To study the infection status of GBV-C virus among HBV, HCV, nonA-E and HCC
      patients, serum of clinical hepatitis patients and HCC patients before operation,
      and the composition in/beside HCC were collected to examine HGV RNA of the
      samples, using HGV RT-PCR method. Results showed that among the clinical patients
      with HBV, HCV, nonA-E and HCC, HGV infection rates were 9% (12/130), 10% (3/30),
      17% (4/24), 0% (0/24) respectively, suggesting that HGV is a hepatitis virus with
      pervasive existence and has high superimposition infection rate with HBV and HCV
      but with little connection with HCC.

PMID- 10921117
TI  - [A novel rotavirus causing large scale of adult diarrhea in Shi Jiazhuang].
AB  - An outbreak of adult diarrhea causing more than 1,000 hospitalized cases among
      graduates in a university in Shi Jiazhuang city (Hebei province), occurred in 10
      28, April, 1997. The non-bacterial pathogenic agent is confirmed as Rotavirus
      first by PAGE. Forteen samples have been demonstrated sharing the same nucleic
      acid electrophoresis pattern of 4-2-1-1-1-1-1. The positive rate was 47% (thirty
      samples have been checked) with no other RV pattern. Dada showed that RV with
      this kind of nucleic acid electrophoresis pattern were responsible for the
      outbreaks acute diarrhea in adults. The novel RV and known ADRV was RT-PCR with
      end-primers 5, 9 of typical ADRV, the positive control typical ADRV's results are
      positive, the novel RV's are negative. Experimental results showed that the novel
      RV did not belong to group B RV, totally different from all the known ARDV. This
      case was the first reported one in Hebei province with an outbreak of adult
      diarrhea not by any known ADRV.

PMID- 10921119
TI  - [Strategy on the prevention and treatment of chronic diseases among residents in
      Dongcheng District, Beijing].
AB  - Chronic diseases, in particular, circulatory diseases characterized by high
      mortality, morbidity, and lack of special treatment have become serious problems
      to the residents living in the Beijing communities. To learn the above mentioned
      diseases among people at the community level and to investigate treatment and
      preventive method concerned studies on chronic circulatory system diseases among
      people living in communities in Dongcheng where few disease were under special
      control studies were carried out between 1981 and 1997. We found that the studied
      residents who had received and adopted a series of preventive measures as health
      education, giving up smoking, reducing alcohol and salt consumption, diet balance
      and practicing physical exercises, had greatly improved their health condition.
      Because of the positive results, we addressed some long-termed suggestions on the
      treatment and prevention for chronic patients with circulatory system diseases
      which is believed to have established a solid ground for the future.

PMID- 10921118
TI  - [Retrospective study on the risk factors in patients with nosocomial bacterial L
      form infection].
AB  - To survey the risk factors of nosocomial bacterial L-form infections, 22 risk
      factors were investigated and analysed with nonconditional logistic regression.
      Resutts showed through single factor regression that cancer, chronic disease,
      primary infection, longer than 3-week hospitalization before the onset of
      nosocomial infection, preventive use of antibiotics longer than 7 days,
      preventive use of cell wall depressive antibiotics, steroid use, anti-tumor drugs
      and urine guide technique were significant factors. Multiple factor regression
      demonstrated that two models including cell wall depressive antibiotics, primary
      infection, urine guide technique cell wall depressive antibiotics, primary
      infection, anti-tumor drugs and longer than 3-week hospitalization before the
      development of nosocomial infection were conjugated properly. It suggested that
      the surveillance of risk factors of nosocomial bacterial L-form infections was
      helpful to control nosocomial infections.

PMID- 10921120
TI  - [Analysis on the risk factors in patients with diabetes mellitus from population
      in mining districts--a population-based case-control study].
AB  - According to data from prevalence study on population from Pingdingshan coal
      mining districts in Henan province, we analysed 174 patients with diabetes
      mellitus(DM) and 3,066 control subjects with normal blood glucose(NGT) by a
      population-based case-control study. After the adjustment of other factors and
      controlled on confounding factors, the results of unconditional logistic
      multivariate regression analysis demonstrated that age, DM history of mother and
      sib, highest BMI through one's life, higher concurrent WHR, higher systolic blood
      pressure, frequently eating Chinese sorghum and legume may serve as independent
      risk factors of DM, their odds ratios(OR) were 2.04, 6.04, 2.24, 1.85, 2.57,
      1.51, 2.22, 1.25 and their population attribution rates (PAR%) were 80.04%,
      7.19%, 3.18%, 37.35%, 48.80%, 8.15%, 3.20%, 10.63% respectively. Higher
      occupational physical activity and frequently eating vegetables of light colour
      might serve as independent protective factors of DM, with ORs 0.89 and 0.50 and
      PAR% of -19.20% and -269.5% respectively. Confounding analysis showed that age
      was both a positive and negative confounding factor to other factors in the
      logistic regression model.

PMID- 10921121
TI  - [Observation and analysis on metabolism of serum calcium and phosphorus in
      patients with pregnancy-induced hypertension].
AB  - 37 patients with obvious pregnancy-induced hypertension, 56 normal pregnant women
      and 40 nonpregnant women in the same age groups were tested on their serum
      calcium(Ca), phosphorus(P) alkaline phosphatase(AKP), parathyroid hormone(PHT)
      and calcitonin(CT). Results indicated that the respective means of serum Ca and
      CT were statistically lower (P < 0.05), while AKP and PTH were higher (P < 0.01)
      than that of normal pregnant women. It was also confirmed that Ca metabolism of
      patients with pregnancy-induced hypertension was obviously abnormal. In addition,
      pathogenesis of pregnancy-induced hypertension was also discussed.

PMID- 10921122
TI  - [An investigation on the risk factors of elderly falls in the countryside old
      folks' homes].
AB  - A case-control study was conducted among 154 cases of falls aged over 60 years in
      18 old folks' homes in the countryside, using 1:1 pair-matching to explore the
      risk factors for the elderly falls. Data were analysed through Linear Logistic
      Regression. Results showed that spouseless, poor physical condition, abnormal
      gait, sufferying chronic situations as hypertension and sequelae of cerebral
      apoplexy, taking anti-hypertension drugs, abnormalities in taking static dynamic
      balance and walking tests in the elderly were main risk factors of the elderly
      falls. The strategies of prevention of the elderly falls were also discussed in
      the paper.

PMID- 10921123
TI  - [Progresses on the study of schizophrenia abroad].

PMID- 10921124
TI  - [Current status of epidemiological study on diabetes mellitus in China].

PMID- 10921126
TI  - Acupuncture at tragus apex for treatment of traumatic ocular muscle paralysis--a
      report of 16 cases.

PMID- 10921125
TI  - Therapeutic effect of abstinence capsule on withdrawal symptoms of heroin
      addicts.
AB  - 435 heroin addicts were treated for 10 days to evaluate the therapeutic
      effectiveness of abstinence capsule on heroin withdrawal symptoms and its main
      adverse actions. Lofexidine was applied in a control group of 48 addicts. The
      single blind method and some determination methods used internationally were
      employed to evaluate the therapeutic effectiveness and adverse actions of the
      drugs. The results showed that the abstinence capsule has better therapeutic
      effectiveness, with less adverse actions, wider safety range, longer time of
      action and less cost than lofexidine.

PMID- 10921127
TI  - Dr. Gao Huiyuan's experience in treating fever.

PMID- 10921128
TI  - The effect of electroacupuncture on auditory P300 potential in mongolism cases.
AB  - In treating children with mongolism (Down's syndrome) with electroacupuncture,
      the latent period of P3 is shortened, which shows that the cerebral reaction to
      external stimulus in classification, encoding and recognition is accelerated.
      Along with the elevated P3 amplitude, the cerebrum is more capable of processing
      the external information, showing improvement of the mental state.

PMID- 10921129
TI  - Treatment of senile diabetic diarrhea with traditional Chinese drugs.

PMID- 10921130
TI  - Effects of acupuncture on the immunological functions in hepatitis B virus
      carriers.
AB  - A contrast study on the effects of manual acupuncture and electroacupuncture was
      conducted in 60 cases of chronic hepatitis B carriers. The results demonstrated
      that the immunological functions, both cellular and humoral, were markedly
      regulated as evidenced by the negative turnover rates of HBsAg, HBeAg, anti-HBc
      and HBcAg, as well as the positive turnover rate of anti-HBe.

PMID- 10921131
TI  - Clinical study on manipulative treatment of derangement of the atlantoaxial
      joint.
AB  - The derangement of the atlantoaxial joint is one of main cervical sources of
      dizziness and headache, which were based on the observation on the anatomy of the
      upper cervical vertebrae, analysis of X-ray film of the atlantoaxial joint, and
      the manipulative treatment in 35 patients with cervical spondylosis. The clinical
      diagnosis of derangement consists of: dizziness, headache, prominence and
      tenderness on one side of the affected vertebra, deviation of the dens for 1 mm-4
      mm on the open-mouth X-ray film, abnormal movement of the atlantoaxial joint on
      head-rotated open-mouth X-ray film. An accurate and delicate adjustment is the
      most effective treatment.

PMID- 10921132
TI  - Acupuncture treatment of angina pectoris.

PMID- 10921133
TI  - Clinical application of moxibustion over point dazhui.

PMID- 10921134
TI  - Treatment of 50 cases of senile dementia by acupuncture combined with inhalation
      of herbal drugs and oxygen.

PMID- 10921135
TI  - Clinical observation on electrothermal acupuncture in treatment of 16 cases of
      vulvar dystrophy.

PMID- 10921136
TI  - The nerve-root-type cervical spondylopathy treated by massotherapy with an
      observation of microcirculation in the affected limb.

PMID- 10921137
TI  - TCM treatment with the modified wendan tang in 40 cases of melancholia.
AB  - Melancholia is a syndrome caused by emotional stress and stagnation of qi,
      involving the liver, affecting the heart and spleen, and leading to disharmony of
      qi of the zang-fu organs. Because of the complicated condition, it is not easy to
      determine the therapeutic principles. In this series of 40 cases, the modified
      Wen Dan Tang (Decoction for Clearing Away Gallbladder-Heat) was used for the
      treatment. Of them, 19 cases were cured, 16 improved, and 5 failed, with total
      effective rate of 87.5%.

PMID- 10921138
TI  - 46 cases of insomnia treated by semiconductor laser irradiation on auricular
      points.

PMID- 10921139
TI  - Effects of acupuncture on the pituitary-thyroid axis in rabbits with fracture.
AB  - PURPOSE: To observe the effects of acupuncture on the pituitary-thyroid axis in
      rabbits with fracture. METHOD: 36 male rabbits with a 3-mm width experimental
      defect in the middle segment of the left radius were randomly divided into the
      treatment group and control group, and the changes in serum T3, T4 and TSH
      contents in different weeks were investigated. RESULTS: Serum T3, T4 and TSH
      contents in the treatment group all were higher than those in the control group,
      with statistically significant differences in the contents of T4 and TSH in the
      second week and T3 content in the fourth week (P < 0.01 or P < 0.05). CONCLUSION:
      The action of promoting union of fracture is possibly related with the pituitary
      thyroid axis.

PMID- 10921140
TI  - Advances in TCM treatment of senile dementia.

PMID- 10921141
TI  - Acupuncture treatment of dysmenorrhea.

PMID- 10921142
TI  - Clinical study on 118 cases of ulcerative colitis treated by integration of
      traditional Chinese and Western medicine.
AB  - 118 cases of ulcerative colitis were treated by integration of traditional
      Chinese and Western medicine. Another 86 cases of ulcerative colitis were treated
      by simple western drugs as controls. The therapeutic effects for both groups were
      observed and compared after two therapeutic courses of 40 consecutive days. As a
      result, 39 cases were cured, 60 cases improved and 19 cases failed, with a total
      effective rate of 84% in the treatment group; in the control group, 15 cases were
      cured, 37 cases improved and 34 cases failed, with a total effective rate of
      60.5%. Statistically, the difference was very significant (P < 0.01). It can be
      concluded that treatment of ulcerative colitis by the integrated method is
      superior to that by simple western drugs.

PMID- 10921143
TI  - A double blind observation for therapeutic effects of the tong luo kai bi tablets
      on rheumatoid arthritis.
AB  - The therapeutic effects of the Tong Luo Kai Bi Tablets [symbol: see text] in 120
      patients with rheumatoid arthritis were observed in this clinical trial by the
      randomized double blind method. Both the observed group and the control group
      each had 60 patients. In the observed group treated with the Tong Luo Kai Bi
      Tablets, 1 case (1.7%) was cured clinically, 27 cases (45.0%) improved markedly,
      26 cases (43.3%) improved, with a total effective rate of 90.0%. In the control
      group treated with Rheumatic Semen Strychni Tablets [symbol: see text], no case
      was cured, 16 cases (26.7%) improved markedly, 33 cases (55.0%) improved, with a
      total effective rate of 81.7%. Statistical data showed the Tong Luo Kai Bi
      Tablets had much better therapeutic effectiveness clinically than the Rheumatic
      Semen Strychni Tablets (P < 0.05).

PMID- 10921144
TI  - Treatment with jimei'an of nongonococcal urethritis caused by Chlamydia and
      Ureaplasma urealyticum.

PMID- 10921145
TI  - Prof. Kong Lingxu's experience in TCM treatment of insomnia.

PMID- 10921146
TI  - Clinical observation on treatment of diabetic peripheral neuropathy with
      reinforced tianma duzhong capsule.

PMID- 10921147
TI  - Fuzi xiexin tang for treatment of intractable pediatric diseases.

PMID- 10921148
TI  - The third lumbar transverse process syndrome treated by electroacupuncture at
      huatuojiaji points.
AB  - 32 cases of the third lumbar transverse process syndrome were treated mainly by
      electroacupuncture at Huatuojiaji points of the first and second lumbar
      vertebrae, and another 30 cases of the syndrome by conventional acupuncture as
      the controls. The results showed that treatment by electroacupuncture at
      Huatuojiaji points was superior in analgesic effect and clinical total effective
      rate to that by conventional acupuncture. It is considered that the mechanism of
      treatment by electroacupuncture at Huatuojiaji points is related to the trunk of
      posterior ramus of the spinal nerve where the points are located.

PMID- 10921149
TI  - Treatment of postapoplectic thalamic spontaneous pain by electroacupuncture at
      huatuojiaji points.
AB  - The authors have treated 30 cases of postapoplectic thalamic spontaneous pain
      (PTSP) by electro-acupuncture at Huatuojiaji points (Extra), with the other 30
      cases of PTSP treated by oral administration of carbamazepine as the controls.
      The total effective rate was 90% in the acupuncture group, and 86.7% in the
      control group. The difference in the total effective rate between the two groups
      was not statistically significant (P > 0.05), suggesting that electroacupuncture
      at Huatuojiaji (Extra) is a better therapy for PTSP.

PMID- 10921150
TI  - A comparative observation on comprehensive scalp--acupuncture treatmentof
      ischemic apoplectic hemiplegia.

PMID- 10921151
TI  - 100 cases of intractable migraine treated by acupuncture and cupping.

PMID- 10921152
TI  - Arthralgia treated by acupuncture within "Chifu" area.

PMID- 10921153
TI  - Prof. Xiao Shaoqing's experience in application of point-through-point
      acupuncture technique.

PMID- 10921154
TI  - Treatment of epigastralgia by external application of huweigao at shenque point.
AB  - 140 cases of epigastralgia were divided into two groups at random. The 100 cases
      in the treatment group were treated with Huweigao externally applied at Shenque
      (Ren 8), and the 40 cases in the control group by oral administration of Weinaian
      capsule. After a one-month treatment, the total symptom-relieving rate and the
      gastroscopy-proved effective rate were 94.0% and 52.6% respectively in the
      treatment group, much superior to those in the control group.

PMID- 10921155
TI  - 16 cases of scalenus syndrome treated by massage and acupoint-injection.

PMID- 10921156
TI  - A survey on acupuncture treatment of peripheral nerve injury.

PMID- 10921157
TI  - Progress in the treatment of nerve-root-type cervical spondylosis with Chinese
      herbal drugs.

PMID- 10921158
TI  - TCM differential treatment of angina pectoris--an illustrative case report.

PMID- 10921159
TI  - What should be kept in mind for management of the toxic side-effects induced by
      postoperative chemo- and radiotherapy for ovarian tumor?

PMID- 10921160
TI  - The effect of zhu yu hua tan tang on intracranial pressure in case of acute
      cerebral hemorrhage.
AB  - The therapeutic effect of Zhu Yu Hua Tan Tang ([symbol: see text] Decoction for
      removing blood stasis and resolving phlegm) plus general and modern treatment on
      acute cerebral hemorrhage in 44 cases, and the pressure-lowering effect of Zhu Yu
      Hua Tan Tang and mannitol in 20 cases of acute cerebral hemorrhage in the basilar
      region, and in rabbits with experimental encephaledema induced by injection of
      olive oil into the common carotid artery were observed in this study. The results
      showed that Zhu Yu Hua Tan Tang plus general treatment can better improved the
      conscious state of the patients than western medicine, and it can make the
      intracranial pressure drop clinically by 40.44%. The intracranial pressure
      lowering effect of Zhu Yu Hua Tan Tang, though slow, is smooth and long-lasting
      without any rebound phenomenon, as compared to those of mannitol. Similar results
      were found in animal experiments, but the intracranial pressure-lowering
      amplitude of Zhu Yu Hua Tan Tang was stronger than that of mannitol. The
      difference between the clinical and experimental results needs to be further
      studied.

PMID- 10921161
TI  - A clinical study of yi zhi capsules in prevention of vascular dementia.
AB  - The raised score in the revised Hasegawa dementia scales (HDS) demonstrated that
      the effect of Yi Zhi Capsules (YZC) in treating loss of intellectual function
      after cerebrovascular diseases was significantly better than that of the western
      drug Piracetam [symbol: see text] (P < 0.01). The morbidity of vascular dementia
      was much lower in the treatment group than that of the control group (P < 0.05)
      after a one-year follow-up; and the blood lipid level and some indexes in
      rheological examinations were also improved significantly (P < 0.05, or < 0.01).
      The data indicate that YZC is a relatively good preparation for prevention of
      vascular dementia.

PMID- 10921163
TI  - Clinical study on treatment of alcoholic hepatopathy with qing gan jie jiu yin.

PMID- 10921162
TI  - Clinical observation and experimental study on compound hypoglycemic decoction
      for hyperglycemia.
AB  - PURPOSE: To observe the clinical efficacy of Compound Hypoglycemic Decoction
      (CHD) and its effect on serum total cholesterol in model mice. METHOD: The paired
      t test was used to analyze the data recorded before and after administration of
      drugs for hyperglycemia induced by intraperitoneal injection of 75% egg yolk
      emulsion in experimental mice. CHD and Fenofibrate were administered as
      prevention measures. RESULTS: The total effective rate of serum total cholesterol
      (TC) decrease in 60 cases of hyperglycemia was 86.66% and that of serum total
      triglyceride (TG) decrease was 81.81%. The total effective rate of high-density
      lipoprotein-cholesterol (HDL-C) increase was 75%. The decrease in TC and TG, and
      the increase of HDL-C after treatment by in-group comparison were all significant
      (P < 0.05). 21.9% and 22.2% decrease in the total cholesterol was respectively
      found in the CHD and Fenofibrate groups (both P < 0.05), with no significant
      difference. CONCLUSION: The hypoglycemic action of Compound Hypoglycemic
      Decoction was remarkable in clinical practice, and it is very effective in
      preventing hyperglycemia in experimental mice.

PMID- 10921164
TI  - Effects of the integrated TCM-WM treatment of nephrotic syndrome on growth and
      sexual development.
AB  - Fifty children with nephrotic syndrome were treated by using herbal drugs for
      nourishing yin to reduce pathogenic fire, strengthening qi and tonifying the
      kidney, and promoting blood circulation and removing blood stasis in combination
      with glucocorticoid and immunodepressant. The body height, secondary sex
      characters, age of the first spermatorrhea for male and of menarche for female
      children, bone age measured with roentgenograms on the left wrist in 50 cases of
      the treatment group were compared with those in 31 cases of the control group
      treated by glucocorticoid and immunodepressant. The results showed that the delay
      of growth and sexual development as side-effects of glucocorticoid and
      immunodepressant were markedly reduced by the integrated TCM-WM treatment.

PMID- 10921165
TI  - The time-effect relationship of central action in acupuncture treatment for
      weight reduction.
AB  - PURPOSE: To study the time-effect relationship of action of acupuncture on the
      satiety center of ventromedial nucleus of hypothalamus (VMH) in rats with
      experimental obesity. METHODS: Microelectrode recording method of nerve cells and
      stereotaxic technique for brain were adopted with discharge frequency (Hz/s) of
      nerve impulse in VMH as the index, and the time-effect of acupuncture action in
      different periods between groups were observed. RESULTS: Electric activity in
      acupuncture group was higher than in the obesity model group (P < 0.001) and the
      normal group (P < 0.01) respectively, and the curve of acupuncture action within
      2 hours showed irregular fluctuation. CONCLUSION: Acupuncture can increase
      excitability of the satiety center, with a better long-term effect.

PMID- 10921167
TI  - Treatment of 86 cases of facial spasm by acupuncture and pressure on otopoints.
AB  - The combined method of acupuncture with pressure on otopoints (the combination
      group) was used to treat 86 patients with facial spasm; and simple acupuncture
      and simple pressure on otopoints were respectively applied in the other two
      groups of patients as controls. The total effective rates of the combination
      group, the acupuncture group and the pressure on otopoints group were 95.4%,
      92.1% and 62.5% respectively; and the cure rates were 38.4%, 15.8% and 5%
      respectively. The differences in results of the three groups show statistically
      marked significance, indicating that the therapeutic effectiveness of the
      combined method of acupuncture with pressure on otopoints is better than the
      other two therapeutic methods.

PMID- 10921166
TI  - Acupuncture treatment of bulbar palsy--a report of 54 cases.

PMID- 10921168
TI  - Twenty-three cases of postherpetic neuralgia treated by acupuncture.

PMID- 10921169
TI  - Clinical application of taichong acupoint.

PMID- 10921170
TI  - Twenty-seven cases of spleen-qi deficiency syndrome treated by heat-producing
      needling at zusanli.

PMID- 10921171
TI  - Fifty cases of gastroptosis treated by moxibustion therapy.

PMID- 10921172
TI  - The thinking on TCM differential treatment of congestive heart failure.

PMID- 10921173
TI  - A summary of clinical treatment for 58 cases of hemiplegia with electro
      acupuncture and massage.

PMID- 10921174
TI  - Application of theories of free radicals and electron spin resonance for research
      of traditional Chinese medicine.

PMID- 10921175
TI  - Effect of stimulation of shenshu point on the aging process of genital system in
      aged female rats and the role of monoamine neurotransmitters.
AB  - In this experiment, among some aged female rats aged over 18 months, and young
      female rats aged 3 months whose central noradrenergic nerve endings were injured
      by ventricular injection of 6-hydroxy-dopamine (6-OHDA), it was observed that
      catgut embedding at bilateral Shenshu (UB 23) points could obviously shorten
      sexual cycles, increase the frequency of sexual cycle, and slow down the aging
      process of the genital system in both the aged rats and in the rats with injured
      noradrenergic endings. After electroacupuncture (EA) at Shenshu (UB 23) points in
      the aged rats, the frequency of neuronal discharges in locus coeruleus (LC) was
      elevated and the activating rate of LC to neurons in the medial preoptic area
      (MPOA) of the hypothalamus was increased, while obvious effect on nucleus raphes
      magnus (NRM) and the effect of NRM on MPOA were not marked. It is suggested that
      stimulation of Shenshu (UB 23) point can strengthen the excitability of
      noradrenergic neurons, activate the ascending pathway of the brain stem-
      hypothalamus, raise the catecholamine (CA)/5-hydroxytryptamine (5-HT) ratio in
      the hypothalamus of the aged rats, so as to delay the aging process of the
      genital system.

PMID- 10921176
TI  - A survey on TCM treatment of drug-induced postabortal colporrhagia.
AB  - Drug postabortal colporrhagia is one of the major problems that need to be solved
      in gynecoiatry. It is shown in the literature that TCM treatment of this disease
      has achieved quite good therapeutic effects. It is my opinion that the following
      works should be done for a better therapeutic effect: 1) study further the
      pathogeneses of the disease; 2) stipulate a unified criteria for typing,
      diagnosis and treatment; 3) develop specific prescriptions and new forms of
      preparation; and 4) further efforts should be also made on the other TCM
      therapies, such as acupuncture, physiotherapy, and massotherapy.

PMID- 10921177
TI  - Survey on radiosensitizing effects of Chinese drugs.

PMID- 10921178
TI  - [In Process Citation]

PMID- 10921179
TI  - [Comparison of transperitoneal versus extraperitoneal laparoscopic para-aortic
      lymphadenectomy: randomized experimental study].
AB  - OBJECTIVES: The objective of this study was to compare the risk of adhesion
      formation and the site of postoperative adhesions after transperitoneal versus
      extraperitoneal laparoscopic paraaortic lymphadenectomy. MATERIAL AND METHOD: A
      prospective randomized trial was conducted on 66 pigs, submitted to
      transperitoneal (n = 33) or extraperitoneal (n = 33) laparoscopic paraaortic
      lymphadenectomy. The efficacy and the intra and postoperative morbidity (adhesion
      score taking into account the number of adhesions and the surface area involved)
      of each approach were compared. The site of postoperative adhesions in relation
      to a simulated external irradiation field was determined by a stereo-localization
      system (Syslav) on 20 pigs. RESULTS: No statistically significant difference was
      observed between the two techniques in terms of operating time, number of lymph
      nodes removed, and intra and postoperative morbidity except for lymphoceles and
      adhesions. No case of lymphocele was observed in the transperitoneal group versus
      13 cases (43.33%) in the extraperitoneal group (P = 0.0002). Final total adhesion
      score was 76% (n = 22) in the transperitoneal group versus 63.33% (n = 19) in the
      extraperitoneal group. Adhesion score specific to the operative site was 76% (n =
      21) in the transperitoneal group versus 43.33% (n = 13) in the extraperitoneal
      group (P = 0.04). A statistically significant difference was observed between the
      two approaches in terms of final total adhesion score (P = 0.008) or adhesion
      score specific to the operative site (P = 0.0005). The stereolocalization study
      showed that almost all adhesions were situated in the paraaortic external
      irradiation field after transperitoneal laparoscopy, while adhesions were
      predominantly situated outside this field after extraperitoneal laparoscopy.
      CONCLUSIONS: Extraperitoneal laparoscopy generates significantly fewer adhesions
      in the paraaortic irradiation field and should have a risk of radiation enteritis
      less important than transperitoneal laparoscopy.

PMID- 10921180
TI  - [Substernal goiter. Report of 212 cases].
AB  - AIM OF THE STUDY: The aim of this retrospective study was to report the results
      of the surgical treatment in a series of 210 patients operated on for substernal
      goiters. PATIENTS AND METHOD: From 1982 to 1996, 210 patients with substernal
      goiters, including 80% of women, were operated on via a cervical approach in 208
      cases, via a sternotomy in two cases. Two patients with operative contra
      indications were not operated on. Twenty-five were operated on for a substernal
      recurrence of a goiter. In 160 cases, extraction of the substernal portion was
      easy. In 48 cases, removal of the substernal portion was facilitated by the
      discovery of the recurrent nerve at its entering into the larynx and a downward
      dissection of the tracheal attachments of the lobe. The complete dissection of
      the cervical portion made easier the ascension of the substernal portion even in
      very large substernal components. RESULTS: Three papillary carcinomas were
      diagnosed. A transient laryngeal nerve palsy occurred in 7.2% of the patients and
      a transient hypoparathyroidism in 13.4%, A definitive laryngeal nerve palsy
      occurred in 1.2% of the patients, and a persistent hypoparathyroidism in 2.1%. Of
      the 25 patients who underwent surgery for recurrence of a goiter, three (12%)
      developed a transient laryngeal nerve palsy, one (4%) a permanent nerve palsy,
      four (20%) a transient hypoparathyroidism and one (4%) a persistent hypocalcemia.
      CONCLUSION: CT scan and MRI are the best explorations to evaluate intrathoracic
      extension of substernal goiters. Thyroidectomy was performed via a cervical
      incision in 208 patients and via a sternotomy in two patients only. The complete
      dissection of the cervical portion with discovery of the recurrent nerve at its
      entering into the larynx, facilitates the ascension of the substernal portion
      even in very large substernal goiters.

PMID- 10921182
TI  - [Detection of lymphatic metastasis from malignant melanoma after identification
      of the sentinel node by preoperative lymphoscintigraphy and intraoperative
      radioisotopic detection].
AB  - OBJECTIVES: The aim of this study was to evaluate the detection of the first
      lymph node draining the primary tumour site, using a radioisotopic mapping alone
      and to determine whether a preoperative lymphoscintigraphy using technetium
      sulfur colloid and a hand-held gamma detecting probe could improve the detection
      of the sentinel lymph node (SLN) in melanoma. PATIENTS AND METHOD: From January
      to December 1998, 36 patients with a cutaneous melanoma larger than 0.75 mm,
      stage I TNM were included in this prospective study. Mean Breslow was 1.85 mm.
      The distribution of melanoma was head and neck (n = 9), trunk (n = 7), upper
      extremities (n = 4), lower extremities (n = 16). Preoperative lymphoscintigram
      and intraoperative detection were used. The first hot lymph node was supposed to
      be the SLN. RESULTS: In all cases, a lymph node was found and nine patients had
      more than one SLN (average number of SLN per patient: 1.25). Aberrant drainages
      were found in seven patients (19.4%): 1 in-transit lymph node, three paradoxical
      bassins, three bypasses). Four out of 36 patients had lymph node metastases and
      underwent elective lymph node dissection. CONCLUSION: The radio-isotopic
      technique used alone for the identification of the SLN is efficient in melanoma
      with a 100% detection rate in this short series.

PMID- 10921181
TI  - [Kidney cancers with supra-diaphragmatic invasion. Surgical treatment using
      extracorporal circulation with heart arrest].
AB  - STUDY AIM: The study aim was to report results of nephrectomy with resection of
      cavo atrial thrombus in 6 patients with a renal carcinoma and supra-diaphragmatic
      vena cava extension and to discuss limits of the surgical indications. PATIENTS
      AND METHOD: Six patients, five adults (mean age: 57 +/- 10 years) and a four-year
      old girl, were operated on for a renal cell carcinoma with supra-diaphragmatic
      vena cava extension. The venous extension was detected in all cases by abdominal
      ultrasonography. The superior extent of the thrombus was effectively visualized
      by CT scan in three cases, and by ultrasonography and magnetic resonance imaging
      in all cases. All the patients were operated on, using cardio-pulmonary bypass,
      without circulatory arrest, four in normothermia, two in moderate hypothermia at
      28 degrees C. RESULTS: Hospital mortality was 0%. Average intensive care unit
      stay was 3.8 days. During the following period, all the patients developed
      metastatic disease. Mean survival rate of the five adult patients who had loco
      regional invasion was 9.4 months (range: 6 to 19). The young girl underwent a
      wedge excision of two pulmonary metastases one year later and was still alive 7
      years later. CONCLUSIONS: With cardio-pulmonary bypass, surgical resection of
      cavo-atrial thrombi may be performed with a low mortality and morbidity rate but
      late results were disappointing. Surgery should be limited to patients without
      loco-regional invasion or distant metastatic disease, and therefore accurate
      preoperative staging is mandatory.

PMID- 10921183
TI  - [Posterior rectopexy in total rectal prolapse-].
AB  - STUDY AIM: The aim of this retrospective study was to report the results of
      posterior Orr-Loygue rectopexy in 55 patients operated on for rectal prolapse.
      PATIENTS AND METHOD: From 1986 to 1997, 114 patients were operated on for rectal
      prolapse and 55 had an Orr-Loygue operation. There were 47 women and 8 men (mean
      age: 55 years). Twenty-five patients (45%) had fecal incontinence, 26 (47%)
      described preoperative 'constipation'. The procedure was performed under general
      anesthesia, through laparotomy in 51 patients, through laparoscopy in 4 patients.
      Resection of sigmoid colon was associated to rectopexy in four patients. RESULTS:
      Mortality rate was 0 and morbidity rate 12%. Mean hospital stay duration was 13.5
      days. Mean follow-up was 63 months and at the end of the study, four patients
      (7%) had recurrence, 5/25 patients had still incontinence; 55% of the patients
      had unchanged postoperative bowel function, 22% described improvement (including
      the four patients with resection-rectopexy) but 38% (21/55) suffered from
      postoperative 'constipation'. The rate of 'constipation' induced or majored by
      rectopexy was 22% but the functional trouble described appeared often complex.
      CONCLUSION: Posterior Orr-Loygue rectopexy is the operation recommended for
      patients in good general condition, especially if fecal incontinence is
      associated. In the course of the procedure, preservation of pelvic nerves and
      hypogastric plexus, and positioning of the strips not too tight between the
      anterolateral rectal walls and promontory must be emphasized. Posterior Orr
      Loygue rectopexy is contraindicated when general anesthesis is too risky and when
      bowel dysfunction and/or rectal exoneration dysfunction are present.

PMID- 10921184
TI  - Does previous endoscopic treatment affect the outcome of laparoscopic Heller
      myotomy?
AB  - STUDY AIM: Aim of this study was to assess symptomatic and objective outcome in
      patients undergoing laparoscopic Heller myotomy after unsuccessful endoscopic
      treatment, compared to patients having primary surgery. PATIENTS AND METHOD:
      Between November 1992 and December 1998, 92 patients with esophageal achalasia
      underwent laparoscopic Heller myotomy and Dor fundoplication. Intraoperative
      endoscopy was routinely performed. Sixty patients had primary surgery (PS); 32
      patients had surgery after unsuccessful pneumatic dilatation (PD) (n = 22), or
      botulinum toxin (Botox) injection (n = 10). RESULTS: The mean operative time and
      the incidence of postoperative dysphagia were similar in the two groups. The
      incidence of intraoperative mucosal tears was 5% in the PS group and 12.5% in the
      PD/Botox group (P = NS). Mucosal tears occurred more frequently during the first
      30 operations (17% vs 3.2%, P < 0.05). Median follow-up was 28 months (range 4
      76). An abnormal esophageal acid exposure was documented in 2 patients in the PS
      group (7.7%), and in two patients in the PD/Botox group (13.3%) (P = NS). Lower
      esophageal sphincter pressure significantly decreased in both groups (P < 0.01).
      The mean percentage of radionuclide residual activity in the esophagus at 1 and
      10 minutes significantly decreased in both groups (P < 0.01). CONCLUSION: There
      is only a trend, although not statistically significant, towards an increased
      risk of complications and adverse effects in patients previously treated by PD
      and/or Botox. The higher incidence of mucosal tears during the first 30
      operations suggests the effect of the learning curve.

PMID- 10921185
TI  - [Highly selection portal decompression for ruptured esophageal varices: study of
      a series of 122 cases with long-term results].
AB  - STUDY AIM: The aim of this retrospective study was to report the results, with a
      minimum 10-year follow-up, of highly selective portal decompression (HSPD)
      realized in order to prevent bleeding recurrences from esophageal or gastric
      varices in a series of 122 cirrhotic patients. PATIENTS AND METHOD: From January
      1980 to February 1997, 122 patients (85 men and 37 women, mean age: 50.4 years)
      with liver cirrhosis stage A (n = 6), B (n = 50), C (n = 6) according to Child
      classification, were operated on for bleeding varices after a delay in 106
      patients, on emergency in 16 patients. The HSPD included a double vascular
      ligature (splenic artery ligature in case of hypersplenism [n = 42] and high
      perigastric veins ligature) and a double tissular stapling (low esophagus
      transection and valvuloplasty). Other associated procedures were performed
      including cholecystendesis in 21 patients. RESULTS: Perioperative mortality rate
      was 8% (n = 10). There was no anastomotic leakage but anastomotic stenosis in ten
      patients treated by dilatation. Three patients only out of 109 (2.5%) were lost
      for follow-up. Portocaval encephalopathy was not observed in any patient. Global
      survival rate was 60% at 5 years and 45% at 10 years. The mortality rate related
      to recurrent esophageal varice bleeding was 11% and related to hepatocellular
      failure 18.5% during the entire follow-up. CONCLUSION: HSPD appears to be the
      best procedure in cirrhotic patients for the prevention of recurrent esophageal
      varice bleeding. Preservation of portal pressure within the cirrhotic liver
      (whereas it is reduced in varices) contributes to the preservation of
      hepatocellular function, avoiding portocaval encephalopathy.

PMID- 10921186
TI  - [Abdominopelvic ultrasonography in suspected acute appendicitis: prospective
      study in adults].
AB  - STUDY AIM: The aim of this prospective descriptive study was to evaluate the
      accuracy of abdomino-pelvic ultrasonography in suspected acute appendicitis in
      adults. PATIENTS AND METHODS: From March to July 1998, 100 consecutive patients,
      63 women, 37 men (mean age: 25 years), after examination by a visceral surgeon
      for suspected acute appendicitis, had an abdominal ultrasonography (US)
      examination with high frequency transducer (7.5 to 9 MHz). The US examination
      concerned appendice, periappendicular tissues and neighbouring organs. The US
      data were correlated with the histopathologic findings in operated on patients,
      and with the clinical and biological follow up in non operated patients. RESULTS:
      Fourty-seven patients had acute appendicitis; 53 were operated on and 47 non
      operated. Analysis of US data revealed sensitivity 91.5%, specificity 94.3%,
      positive predictive value 93.5%, negative predictive value 94.3%, accuracy 93%;
      75% of the other diagnosis were found by US. CONCLUSION: Systematic abdominal
      ultrasonography in suspected acute appendicitis is recommended in adults.

PMID- 10921187
TI  - [Interest in several surgeries for serious abdominal trauma].
AB  - Abbreviated laparotomy and planned reoperation(s) is a new concept in severely
      injured patients with multivisceral failure by hemorrhagic shock, coagulopathy
      and hypothermia. The aim of an abbreviated laparotomy is to control hemorrhage,
      prevent digestive contamination and close the abdominal wall without tension.
      After a delay for reanimation during 24 to 96 hours, discovery of unknown lesions
      and anatomic reconstruction will be possible through planned reoperation in
      better conditions. Emergency reoperation for hemorrhage and abdominal
      hyperpression severely worsens prognosis.

PMID- 10921188
TI  - [Dieulafoy's duodenal ulcer. Report of two cases].
AB  - Two cases of Dieulafoy's ulcer of the duodenum revealed by a severe digestive
      bleeding and histologically proved are reported. It is a rare localization of a
      rare disease which is particular by the presence of an abnormal vessel in the sub
      mucosa layer of the digestive wall. Both patients were operated on and
      successfully treated by excision suture.

PMID- 10921189
TI  - [The role of endoscopic treatment of complications of chronic pancreatitis].
AB  - This review outlines the indications and results of endoscopic management in the
      complications of chronic pancreatitis. Symptomatic obstructions of the main
      pancreatic duct can be treated by endocanalar prosthesis in case of fibrous
      stenosis and by extracorporeal shock wave lithotripsy in case of intraductal
      obstructive stones. Symptomatic or large pseudocysts have to be treated and may
      be treated by placement of transgastric or transduodenal endoprosthesis for
      pseudocysts protuding into the digestive tract and by using transpapillary
      endoprosthesis for communicating pseudocysts. Endoscopic treatment of ductal
      disruptions is difficult and generally requires combined techniques. Symptomatic
      biliary stenosis can be temporary treated using biliary endoprothesis. Short and
      long term results and complications of these different procedures are analysed.
      In the absence of controlled studies, the role of endoscopic treatment in
      comparison to surgical treatment is not well defined. Present indications for
      either approach can be discussed on an individual basis.

PMID- 10921191
TI  - [Joachin Albarran (1860-1912)].

PMID- 10921190
TI  - [Techniques to improve the accuracy of CT-guided abdominal biopsy].
AB  - STUDY AIM: The aim of this paper is to present an overview of the various
      technical progresses made in the field of CT-guided abdominal biopsies. Recent
      improvements allowed to markedly increase the efficiency of biopsies and to
      decrease the number of complications. The main innovations concern the guidance
      technique itself with the availability of ultra-fast CT systems, the development
      of automated biopsy systems, which allow to improve the size and quality of
      tissue samples and numerous technical tricks, allowing an easier access to target
      lesions, either in patient positioning or in displacement of anatomical
      structures. A better management of tissue samples favored by a close
      collaboration with pathologists is also mandatory. The last section of the paper
      is an overview of the rare complications of CT-guided biopsies.

PMID- 10921192
TI  - [Adjuvant chemotherapy in stomach cancer. Meta-analysis].

PMID- 10921193
TI  - [Open or laparoscopic surgery for inguinal hernias? Randomized trial].

PMID- 10921194
TI  - [Hepatectomy for hepatocellular carcinoma: the role of the surgeon in long-term
      survival].

PMID- 10921195
TI  - A theoretical design of a flattening filter to improve field uniformity of a
      superficial therapeutic X-ray beam.
AB  - A Monte Carlo model has been developed using the MCNP code to aid the design of a
      flattening filter, to improve field uniformity of a superficial x-ray machine.
      The machine is operating at 90 kV and filtered with a 1.1 mm aluminium filter. In
      the theoretical simulation the original flat filter was replaced by a varying
      thickness filter to improve the uniformity across field sizes 20, 5 and 2 cm
      diameter as well as hardening the beam. Simulation results showed that flatness
      of the beam profile was improved for the 20 cm field size from +/- 7.3% to +/-
      1.1% across the anode/cathode direction and from +/- 7.7% to +/- 3.2% in the
      anode/cathode direction. For the 5 cm field size the improvement was from +/-
      4.6% to +/- 3.1% and from +/- 5.5% to +/- 3.4%, and for the 2 cm field size from
      +/- 3.1% to +/- 2.4% and from +/- 10.2% to +/- 9.5%, in the same directions,
      respectively. Beam quality simulations were made and the original half-value
      layer was reduced from 2.21 +/- 0.09 mm aluminium to 2.04 +/- 0.09 mm aluminium.
      The study demonstrated that it was possible to build a filter capable of
      flattening the beam profile for different sized applicators without significantly
      changing the penetrating ability of the beam.

PMID- 10921196
TI  - Guidance levels for diagnostic radiology in Victoria. Radiation Safety Unit,
      Department of Human Services, Melbourne, Australia.
AB  - Guidance levels for radiation doses in diagnostic radiology for average size
      patients have been developed for use in the state of Victoria. The guidance
      levels were determined from the results of surveys of patients in hospitals and
      private radiology centres in Victoria. Guidance levels have been developed for
      the following procedures: neonate chest AP; several plain film paediatric
      procedures; several plain film adult procedures; fluoroscopy equipment; and CT
      procedures. The guidance levels are compared with those recommended in other
      countries.

PMID- 10921198
TI  - The 1998 Australian external beam radiotherapy survey and IAEA/WHO TLD postal
      dose quality audit.
AB  - The results of an updated Australian survey of external beam radiotherapy centres
      are presented. Most of the centres provided most of the requested information.
      The relative caseloads of various linear accelerator photon and electron beams
      have not changed significantly since the previous survey in 1995. The mean age of
      Australian LINACs is 7.1 years and that of other radiotherapy machines is 14.7
      years. Every Australian radiotherapy centre participated in a special run of the
      IAEA/WHO TLD postal dose quality audit program, which was provided for Australian
      centres by the IAEA and WHO in May 1998. The dose quoted by the centres was in
      nearly every case within 1.5% of the dose assessed by the IAEA. This is within
      the combined standard uncertainty of the IAEA TLD service (1.8%). The results
      confirm the accuracy and precision of radiotherapy dosimetry in Australia and the
      adequate dissemination of the Australian standards from ARL (now ARPANSA) to the
      centres. The Australian standards have recently been shown to agree with those of
      other countries to within 0.25% by comparison with the BIPM.

PMID- 10921197
TI  - Verification of the dose distribution for 192Ir mould treatments using
      radiochromic film and LiF:Mg,Cu,P TLDs.
AB  - Radioactive moulds are an effective way of treating skin lesions. The aim of the
      study was to verify the dose distribution in a low dose rate 192Ir hand mould
      treatment using radiochromic film and LiF:Mg,Cu,P TLDs. Measurements were
      compared with two computerised treatment planning systems--Theraplan VO5B and
      ADAC Pinnacle3 V4.0b. Radiochromic film measured doses that were typically 25-30%
      lower than the TLD and planning computer doses (which agreed within +/- 5%).
      However, radiochromic film provided a two-dimensional map, which is particularly
      useful for dose distributions that are difficult to predict. This was
      demonstrated in the effects of adding thumb shielding to the hand mould. TLD
      results provided only point dose verification. Dose rates to the inner surface of
      the thumb were reduced from 15-20 cGy/hr to 2-4 cGy/hr by using 7.5 mm lead
      shielding. This is consistent with three half value layer reductions. For
      unshielded treatments, TLD results agreed with the treatment planning computers
      all within +/- 13%, including an uncertainty of +/- 10% on the source strength
      certificate for the activity. Due to the detector's sensitivity, miniaturisation
      would be the next approach for further more accurate verification with
      LiF:Mg,Cu,P TLDs.

PMID- 10921199
TI  - Film based scatter measurement in mammography.
AB  - Film based measurements of scatter to primary ratio (s/p) have been made using
      the "beam stop" technique. Phantom material, radiographically equivalent to 100%
      glandular tissue, 100% adipose tissue and 50% glandular: 50% adipose tissue was
      used. These measurements have been made at 25 and 28 kVp for non grid and 28 and
      30 kVp with grid for phantom thicknesses varying from 3 cm to 7 cm and 'D shaped'
      field sizes varying from 80 to 290 cm2. Results indicate that s/p is
      predominantly uniform across a mammographic image with a reduction towards the
      edge of the phantom. The values for s/p agree with previously published values
      determined from Monte Carlo calculation. Scatter primary ratio was found to be
      directly proportional to phantom thickness with little effect from field size.
      The effect of beam energy was significant in the non-grid case but reduced in
      significance with the use of a grid. The average measurement error was estimated
      at 4.5%. No variation in scatter primary ratio was detected between glandular and
      adipose phantom materials in this study.

PMID- 10921200
TI  - A prevalence survey of iron deficiency and iron deficiency anaemia in pregnant
      and lactating women, adult males and pre-school children in Zimbabwe.
AB  - OBJECTIVE: To determine the prevalence of iron deficiency and iron deficiency
      anaemia (IDA) in selected population groups in Zimbabwe. DESIGN: The study was a
      cross sectional, household prevalence survey. A structured questionnaire was used
      to interview study participants to elicit information on risk factors associated
      with iron status and IDA. Blood samples were collected for quantitative
      measurement of ferritin in serum and haemoglobin estimation as part of a full
      blood count. SETTING: The study was conducted in four administrative provinces of
      the country, Mashonaland Central, Midlands, Matebeleland South and Matebeleland
      North covering three of the five agro-ecological regions of the country. Thirty
      clusters were randomly selected from 28 enumeration districts. SUBJECTS: The
      multistage sampling technique was applied. The total sample consisted of 3,151
      study participants made up of 746 pregnant women, 800 lactating women, 811 adult
      males and 799 pre-school children. Up to 202 results could not be used in the
      analysis. MAIN OUTCOME MEASURES: R Stoltzfus, emphasizes that haemoglobin
      concentration is the key indicator for IDA surveillance. Serum ferritin levels
      measured against 10 ng/dl for females and 15 ng/dl for males as standards below
      which there is IDA. Serum ferritin levels of over 300 ng/dl above which there is
      iron overload. Haemoglobin levels were based on the World Health Organisation
      standards of 11 g/dl below which pregnant women and preschool children were
      considered to have IDA, 13 g/dl for adult males and 12 g/dl for lactating women.
      The proportion of individual households with protected water supplies, sanitation
      and levels of education as they influence the prevalence of IDA. Dietary habits
      with regards their influence on iron availability. RESULTS: The overall
      prevalence of IDA was 24.1% of the total study sample. Of the preschool children
      surveyed 17.7% had IDA, 33.0% of pregnant women, 29.6% of lactating women and
      16.5% of adult males had IDA. Of the population 9.1% surveyed had evidence of
      iron depletion on the basis of serum ferritin levels. More of the pregnant women
      had iron depletion, 14.8%, compared to adult males with 2.2%. Individuals in
      regions IV and V were much more affected by iron depletion and IDA than their
      counterparts in regions II and III in this study. CONCLUSION: Iron deficiency
      anaemia (IDA) is a problem of public health significance in Zimbabwe and is
      associated with areas of food insecurity. From a policy perspective the
      prevention and control of IDA should be a priority on national nutrition and
      health agenda.

PMID- 10921201
TI  - Detection of rotavirus in children under five years of age presenting with
      diarrhoea at Mapulaneng Hospital at Bushbuckeridge, Republic of South Africa.
AB  - OBJECTIVE: To determine the incidence of Rotavirus infection in children under
      five years of age presenting with diarrhoea. DESIGN: Cross sectional study.
      SETTING: Mapulaneng Hospital, Bushbuckridge, Republic of South Africa. SUBJECTS:
      50 children under five years of age presenting with diarrhoea. MAIN OUTCOME
      MEASURES: Rotavirus seroprevalence. RESULTS: Out of 50, 24 (48%) had detectable
      Rotavirus particles in their stools. The highest incidence of infection was
      observed among the seven to 12 months age group. Out of the 245 positive subjects
      22 (91.7%) were breast fed. CONCLUSION: This study shows that diarrhoea in
      children under five years of age is probably caused by Rotavirus in
      Bushbuckridge. We therefore recommend that all children presenting with diarrhoea
      should be screened for Rotavirus.

PMID- 10921202
TI  - Situation analysis for cervical cancer diagnosis and treatment in Zimbabwe.
AB  - OBJECTIVE: To establish factors influencing early diagnosis and treatment of
      cervical cancer in Zimbabwean women. DESIGN: A cross sectional study. SETTING: A
      random selection of 29 primary health care facilities, 11 district/provincial and
      four tertiary hospitals in Zimbabwe. RESULTS: All the institutions at primary
      health care, district, provincial and tertiary levels had the basic
      infrastructure to perform exfoliative cytology screening (Pap. smear). An average
      of only nine pap. smears per month were performed at primary health clinics and
      at district/provincial and tertiary levels seven and 23 Pap. smears per week were
      done respectively. Infrequent supplies of consumable materials and lack of policy
      guidelines were the most common reasons for not screening women. Surgical
      treatment for cervical cancer was offered in all tertiary hospitals but only 22%
      of provincial hospital had facilities to perform hysterectomy. CONCLUSION AND
      RECOMMENDATIONS: There is an urgent need to improve screening for cervical pre
      cancer in Zimbabwean women with emphasis to provide adequate treatment facilities
      especially at district and provincial Hospitals. A national policy guideline
      should be drawn to address specific ages and frequency of screening for cervical
      cancer.

PMID- 10921203
TI  - Cervical lymphadenopathy at Ga-Rankuwa Hospital (South Africa): a histological
      review.
AB  - OBJECTIVE: The main aim of the study was to review the pathology of lymph nodes
      removed from patients with primary cervical lymphadenopathy. DESIGN: A
      retrospective study. SETTINGS: Department of Anatomical Pathology at Ga
      Rankuwa/Medunsa Academic Complex. SUBJECTS: 568 patients who had cervical lymph
      node biopsy. MAIN OUTCOME MEASURES: Prevalence of different diseases. RESULTS:
      The diagnostic yield was more than 70%. The male to female ratio was 1.4:1.
      Granulomatous diseases constituted 24.3%, with 97.8% of these being caused by
      tuberculosis. Neoplastic diseases were seen in 46% of the cases.
      Lymphoproliferative disorders constituted 24% and metastatic tumours formed 21.3%
      of all the tumours. CONCLUSION: The pattern of disease in cervical
      lymphadenopathy is similar to that of other Third World Countries.

PMID- 10921204
TI  - Genital tuberculosis in childhood: a five year old female patient.

PMID- 10921205
TI  - Papillary carcinoma arising in thyroglossal duct cyst: a case report and
      literature review.

PMID- 10921206
TI  - Personality characteristics of adolescent suicide attempters.
AB  - OBJECTIVE: The purpose of this study was to explore both the personality
      characteristics and the symptoms of personality disorder of adolescent suicide
      attempters, as well as the relationship between personality variables and
      hopelessness in this population. METHOD: Two sample populations were used in this
      study. First, 102 adolescent suicide attempters between 13 and 18 years of age
      completed the Millon Adolescent Personality Inventory (MAPI) and the Hopelessness
      Scale for Children (HSC). A second group of 35 adolescent suicide attempters were
      administered the HSC and the revised Diagnostic Interview for Borderlines (DIB).
      RESULTS: No distinctive personality characteristics or symptoms of personality
      disorders were found. However, affective distress seemed to be the most prominent
      feature in the presentation of these adolescents. Additionally, high scores on
      the HSC were associated with elevated scores on the Personality Style scales of
      the MAPI and higher (more dysfunctional) scores on Affect Regulation on the DIB.
      CONCLUSIONS: The results suggest that clinicians should focus most on the
      personality characteristic of sensitivity and on affect regulation when assessing
      adolescent suicide attempters. In addition, hopelessness is important to
      systematically assess because it appears to be related to a variety of
      dysfunctional personality characteristics that may affect follow-up outcome.

PMID- 10921207
TI  - Developmental aspects of psychological defenses: their relation to self
      complexity, self-perception, and symptomatology in adolescents.
AB  - This study investigated developmental aspects of psychological defenses in
      relation to self-complexity, self-perception, and symptomatology through a
      comparison of two groups of adolescents characterized by defense maturity level
      (i.e., immature versus mature defenses). The Defense Style Questionnaire (DSQ
      78), the Self-Complexity Inventory (SCI), the Self-Perception Profile for
      Adolescents, and the Youth Self Report behavior checklist (YSR) were completed by
      79 high school students ranging in age from 15 to 18 years. Subjects were
      characterized as either employing predominantly mature or immature defensive
      strategies based on median splits of the two defense factors. Dependent variables
      included the Self-Complexity Inventory, The Youth Self Report and the Self
      Perception Profile for Adolescents. The mature defense group (N = 26) reported
      significantly higher self-complexity than the immature defense group (N = 26),
      supporting a developmental approach to defense mechanisms. In general, mature
      defense mechanisms seem to be more adaptive in late adolescence than immature
      defenses as indicated by higher global self-worth and fewer internalizing and
      externalizing symptoms. The findings lend support to the developmental approach
      to the self and highlight the importance of examining psychological indices of
      development independent of chronological age.

PMID- 10921208
TI  - Violence in the schools: clinical issues and case analysis for high-risk
      children.
AB  - School violence in rural communities has gained considerable attention
      nationally. Examined are theoretical considerations involving escape theory, the
      risk and protective factors for school violence, case analyses of recent case
      studies, and discussion of recent school violence involving fatal injuries to
      others. Also discussed are diagnostic issues in understanding children who are at
      risk for school violence and ways school violence maybe managed in the schools.
      Suggestions and recommendations including recommendations provided by the
      National School Safety Center for school personnel are offered, as are steps to
      be taken in creating a safe school environment. This information may be helpful
      to child psychiatry and clinical personnel who provide services to school aged
      children.

PMID- 10921209
TI  - Clinical characteristics and treatment responses in cases diagnosed as reactive
      attachment disorder.
AB  - The aim of our study is to report the relation between pathological care and
      impairment in social interaction, communication, language development, and
      stereotypical behaviors. Fifteen cases (9 boys, 6 girls) who have the symptoms
      listed above and who were misdiagnosed with pervasive developmental disorder
      (PDD), were referred to our clinic for evaluation and treatment. After the cases
      were evaluated by a semi-structured interview, symptoms related to pathological
      care were fortified; maternal depressive symptoms associated with child neglect
      and overexposure to television viewing. The cases and the mothers/primary
      caretakers were treated in a standardized psycho-educational program of 3 months.
      After this period improvements were observed in all of the symptom clusters.
      Twelve cases (80%) had improvements in eye contact. Eleven cases (73.3%) began to
      engage in reciprocal play and ten cases (66.6%) showed social imitative
      behaviors. Six cases (40%) began to form sentences. Stereotypic behaviors
      diminished in six cases (40%) and disappeared in nine cases (60%). According to
      our findings, although the symptoms of PDD and reactive attachment disorder (RAD)
      resemble each other, presence of pathological care and good response to treatment
      in RAD can be important for the differential diagnosis with PDD.

PMID- 10921210
TI  - Factors influencing the evaluation of an article in cancer literature.
AB  - Casual Interpretation of results in a given article has several pitfalls. In
      order to assess the strengths and limitations of a given article several factors
      need to be considered. This review article is intended to list, classify and
      describe briefly the factors that should be considered in the evaluation of an
      article. The three primary criteria which help in proper assessment of an article
      are (1) Accurate and adequate description of material and methods; (2) Data on
      the total sample size and elimination criteria; (3) Statistical methodology
      employed.

PMID- 10921211
TI  - Epstein-Barr virus in nasopharyngeal carcinoma in Indian patients.
AB  - Formalin fixed paraffin embedded tissue blocks from 40 cases of nasopharyngeal
      carcinoma were investigated for the presence of Epstein-Barr virus (EBV).
      Heminested polymerase chain reaction was employed to amplify U 2 region of EBV
      DNA coding for EBNA 2 gene. This is the first study of its kind carried out in
      India. EBV was detected in 28 out of 40 (70%) nasopharyngeal carcinomas. Type A
      EBV was identified in 20 cases (71.4%), type B in 7 cases (25%) and coinfection
      in one case (3.5%). Either type A, or type B EBV, was identified in 22 out of 23
      cases (95.7%) of undifferentiated nasopharyngeal carcinoma and 6 out of 15 cases
      (40%) of non keratinized squamous carcinoma. The higher incidence of EBV in non
      keratinized squamous carcinoma of nasopharynx assumes importance in view of the
      contrary reports in other studies. 26 cases were from Western India, of which 15
      (57.6%) showed presence of type A EBV and 2 (7.6%) type B EBV. From Eastern
      Indian particularly Assam, 4 our of 5 cases showed positivity for type B EBV and
      1 a coinfection. Whereas, from Bihar 3 out of 4 cases showed presence of type A
      EBV. From Middle East (Arabs) type A EBV was detected in 3 out of 5 cases of
      nasopharyngeal carcinomas. Geographically, type A EBV was far more prevalent in
      Western India, while in Eastern India particularly Assam, all five vases were
      positive for type B EBV. Thus, a significant variation in the type of EBV
      infection was observed in nasopharyngeal carcinoma in different ethnic
      populations in India.

PMID- 10921212
TI  - Estimating cancer survival in developing countries. Use of reply-paid post cards
      to augment follow-up information.
AB  - Survival from cancer is one of the indices to evaluate cancer control activities.
      Reliability of survival estimates depends to a large extent on the completeness
      of follow-up information available for patients in the study group. Loss to
      follow-up (LFU) is one of the potential problems introduced in follow-up of
      cancer patients. An attempt is made to improve the follow-up system for reducing
      the LFU of cancer patients by repeatedly sending reply-paid post cards for the
      LFU patients. A total of 353 ovarian cancer patients registered at the Regional
      Cancer Centre, Trivandrum during a three year period and followed-up to a total
      of five years showed 67 percent loss to follow-up. The five-year survival rate of
      this group calculated using Kaplan-Meier method under the assumption that the
      LFU's occurred at random was 75 percent. Efforts to improve the follow-up rate
      for the study population were made through the simple and cost effective method
      of postal enquiry which resulted in a reduction of 63 percent of losses to follow
      up. Incorporation of this information in the data brought about a revised five
      year survival estimate of 55 percent. The reply paid post card system was found
      to be effective in obtaining useful follow-up data. The result shows that LFU can
      be reduced by better design of survival study.

PMID- 10921213
TI  - Brain stem glioma--a study of 111 patients.
AB  - The study analyses 111 patients of brain stem glioma; seen in neurosurgery Dept.,
      AIIMS, N. Delhi, India, from Jan '83 to March '97; 60% of the patients were under
      the age of 15 years, with two peaks in age distribution, 6-10 years & 36-45 years
      & there was slight male preponderance in all age groups. Most common site of
      tumour was pons both in adults & children. Pyramidal & cerebellar signs were more
      frequently seen in children. Duration of symptoms was usually less than six
      months (in 65.5% of cases). Surgical management was attempted in 72 patients with
      post of radiotherapy & chemotherapy, rest of the 39 cases were treated with
      radiotherapy, chemotherapy & antitubercular treatment (if indicated). Improvement
      was seen in 30% patients postoperatively. Outcome was better in patients who were
      treated surgically. Astrocytoma was most common histological diagnosis (62%) &
      glioblastoma was not uncommon & was seen in 10 (13.8%) cases.] We conclude that
      the patients with brainstem glioma can be helped by surgical decompression,
      followed by adjuvant radiotherapy & chemotherapy.

PMID- 10921214
TI  - Clinicopathological profile of cutaneous lymphomas--a 10 year retrospective study
      from south India.
AB  - This is a retrospective study of cutaneous lymphomas (CL) seen over a ten year
      period. (January '88-December '97) in Christian Medical College & Hospital,
      Vellore, S. India. The aims of the study were to describe the clinicopathological
      profile of CL and correlate it with results of immunophenotyping. Thirty three
      patients were included of whom 31 had non-Hodgkin's lymphoma (NHL) and two
      Hodgkin's disease. REAL scheme was used for classification. In the NHL group
      there were 20 patients with cutaneous T cell lymphoma (CTCL), 7 with cutaneous B
      cell lymphoma (CBCL), 1 with anaplastic large cell lymphoma (ALCL) and 3 patients
      were unclassifiable. Mycosis fungoides was the most common CTCL (55.5%). Three
      (15%) of patients had subcutaneous panniculitic T cell lymphoma (SPTL). The
      duration of the disease was significantly longer (P < .05) in patients with MF as
      compared to non MF CTCL and CBCL. One patient with Sezary's syndrome was HTLV 1
      positive. There was no difference in survival (p = 0.86) after diagnosis in the
      three main groups.

PMID- 10921215
TI  - Mastectomized Indian women: psychological sequelae and dynamics of
      underutilization prosthesis.
AB  - With an objective to explore various psychological reactions of mastectomized
      women and to understand dynamics underlying non-utilization or under-utilization
      of prosthesis/reconstruction facility, a sample of 90 women was drawn from
      Government Medical College and Hospital and tested for neuroticism, body-self
      image and physio-psychological complaints. The total sample comprised three
      groups that included 30 mastectomized women (gr. 1); 30 non-mastectomized women
      operated for various other problems (gr. 2); and 30 non-mastectomized normal
      healthy women (gr. 3). They were tested with psychological tools viz., NSQ, BSIQ,
      and SRQN. The obtained data were analysed for one way ANOVAR design.
      Mastectomized women and non-mastectomized operated for other problem women group
      both showed poorer body-self-image than the normal women but no significant
      difference was seen between mastectomized and non-mastectomized women operated
      for other problems. Similar picture emerged for SRQN scores i.e., neuroticism
      measured in terms of psycho-physical/physio-psychological complaints. With
      respect to NSQ scores, mastectomized women were found higher on submissiveness
      scale than the other two groups. Women in general did not show awareness about
      prosthesis or reconstruction facility. Results are interpreted in the light of
      psycho-social coceptualization of a "woman" in Indian psyche. The data seem to
      project a need of cognitive intervention in the treatment of disease.

PMID- 10921216
TI  - Status of lipid peroxidation and antioxidant enzymes in malignant (bronchogenic
      carcinoma) and non-malignant pleural effusions.
AB  - Eighty patients from Chennai Medical College (patients with bronchogenic
      carcinoma) and from Tambaram Tuberculosis Hospital (patients with non-malignant
      pulmonary diseases mainly tuberculosis) in whom the etiologic diagnosis of their
      pleural effusions are confirmed were included in the study. Lipid peroxidation
      (LPO) and activities of antioxidant enzymes were estimated in pleural exudates of
      the two groups. Lipid peroxidation was found to be increased and the status of
      antioxidants were found to be decreased in lung malignant pleural exudates when
      compared to those of non-malignant effusions. The possible reasons for the
      observed results discussed.

PMID- 10921217
TI  - Do all grade I lesions on colposcopy need to be biopsied?
AB  - The present study intends to correlate grade I atypical transformation zone (ATZ)
      on colposcopy with cytology & histology in 51 patients by retrospective data
      analysis. Indications of colposcopy were inflammatory smears with unhealthy
      cervix (37/51). Atypical squamous cells of unknown etiology (2/51) & squamous
      intraepithelial lesions on cytology (12/51). All the patients exhibited grade I
      lesions on colposcopy & underwent directed biopsy. On histology chronic
      cervicitis was the commonest finding 70.6% (36/51) & CIN was found in 19.6%
      (10/51), out of which CIN II-III occurred only in 3.92% (2/51). Overcall rate of
      colposcopy for grade I lesions was 80.39%. Age, parity, the postcoital or contact
      bleeding did not correlate with the histological positivity of the lesions. Grade
      I ATZ with inflammatory smears revealed CIN II-III only in 2.7% (1/37) while with
      low grade SIL cytology there was no moderate or severe dysplasia. However Grade I
      lesions in association with high grade SIL exhibited CIN II-III lesions in 16.6%
      (1/6). Therefore grade I lesions in presence of inflammatory or low grade SIL
      smears can be observed & biopsied only if the changes persist. However
      association of high grade SIL with grade I ATZ calls for immediate biopsy.

PMID- 10921218
TI  - The role of Wobe-Mugos in reducing acute sequele of radiation in head and neck
      cancers--a clinical phase-III randomized trial.
AB  - Oral enzymes act as a potent antiinflammatory, antiedematous agents thereby
      decreasing acute toxigenic effect of radiation and increasing compliance, quality
      of life of our patients. Fifty patients were randomized 25 allocated in enzyme
      and radiotherapy arm, 25 in radiotherapy alone. Pre RT and post RT biopsies were
      taken from both arms. In our study it was found that there was clinical,
      histopathological as well as statistical significant difference in both arms. The
      enzyme arm patients had mucostis of grade I in 76%, grade II in 12%, grade III in
      8% while as 8% had grade I, 68% grade II, 24% had grade III in RT arm alone. In
      enzyme patients skin reactions of grade I in 72%, 20% had grade II, 8% had grade
      III. In control arm 12% had grade I, 76% had grade II, 8% had grade III skin
      reaction.

PMID- 10921219
TI  - Interobserver agreement of the Nottingham histologic grading scheme for
      infiltrating duct carcinoma breast.
AB  - Interobserver agreement of the histologic grading scheme for infiltrating duct
      carcinoma (IDC) of breast was assessed. Three pathologists independently
      evaluated histologic grade using the modified Bloom and Richardson histological
      grading system on 40 cases of IDC breast. Pairwise K value for agreement ranged
      from 0.68-0.83 (median 0.68) for histological grade suggesting substantial
      agreement. Generalized K values were 0.54, 0.34 and 0.36 for tubule formation,
      nuclear pleomorphism and mitotic count respectively indicating moderate and fair
      agreement. Similar levels of agreement were obtained specially in the final
      histologic grade between pathologists routinely reporting histopathology material
      and one pathologist who was not. This was achieved by use of precise guidelines.
      The ease with which this grading system could be applied by pathologists on
      histopathology material will greatly help its acceptability in routine
      histopathology.

PMID- 10921221
TI  - Trends and predictions of cancer incidence cases by site and sex for Mumbai.
AB  - In order to estimate the resources needed for the diagnosis, treatment, follow-up
      and rehabilitation services needed for cancer patients, it is important to know
      the magnitude of common cancers at present and in future. Keeping this view in
      mind an attempt has been made to predict cancer incidence cases for most common
      cancers for Greater Bombay upto the year 2002. The trend analysis is carried out
      for major 30 cancer sites for both the sexes using age incidence data of Greater
      Bombay for the period 1968 to 1987. The age-period-cohort model which was fitted
      to the data for studying trends for each site and sex has also been utilized for
      prediction also. Prediction was based on the assumption that the characteristic
      features of the model estimated from the observed rates would continue to hold
      during the prediction periods. Present trend analysis showed that cancers of the
      tongue, mouth, oropharynx, oesophagus, stomach and larynx in both sexes and
      cervix for females have registered a decline in incidence over a period of
      observation. While, during the same period, cancers of the liver, pancreas,
      bladder, brain and thyroid in both the sexes, breast, endometrium and ovary in
      females, and testis in males showed increasing trends in incidence, while cancers
      of the hypopharynx, lung, bone, connective tissue and lymphomas in both the sexes
      did not show any significant change in the incidence. In males in 1968-1972
      cancer of the oesophagus was the leading cancer, followed by lung, larynx, tongue
      and stomach, while in 1988-2002 cancer of the lung will be the most predominant
      cancer, followed by hypopharynx, oesophagus, prostate and tongue. It is believed
      that the results of the present study will provide a sound basis for planning the
      cancer control, prevention, diagnostics, treatment and rehabilitation in Mumbai
      for the years to come.

PMID- 10921220
TI  - Screening for cancer of uterine cervix and approaches adopted in India.
AB  - Cervical cancer is the leading malignancy among Indian women. It has been
      estimated that in the absence of any control programme, the incident number of
      cervical cancer cases in the country would rise to 140 thousand by the turn of
      this century. Cytology screening remains the main stay for the control of cervix
      cancer. In the present communication the evidence available for screening for
      cancer of cervix has been presented. Difficulties in organising cervical cancer
      screening programmes in India and the alternative approach have been discussed.

PMID- 10921222
TI  - Epidemiology of cervical cancer--a case control study on north Indian population.
AB  - The present case control study on married women with cervical cancer and controls
      (100 each) revealed the association of age at marriage, socioeconomic status,
      education status and parity with cervical cancer but young age at marriage (rr
      3.79) and low socioeconomic status (rr -3.81) emerged as independent predictors
      of disease status.

PMID- 10921223
TI  - Retroperitoneal extraosseous osteosarcoma. A case report and review of
      literature.
AB  - Extraosseous osteogenic sarcoma is a rare and highly malignant neoplasm. A 57
      year old male patient presented with a mass in the abdomen involving the left
      lumber region. The ultrasound and computerized tomography (CT) scan showed a
      large mass arising from upper pole of the left kidney. Left radical nephrectomy
      was performed in April 1995. Histopathology report revealed a high grade
      extraosseous osteogenic sarcoma. Patient was disease free for 23 months. Although
      the prognosis is grave, aggressive surgical treatment with adjuvant therapy helps
      in prolonging the survival.

PMID- 10921224
TI  - Squamous cell carcinoma of ascending colon. A case study.
AB  - We report here a case of squamous cell carcinoma of Ascending colon occurring in
      a 58 year old male. Squamous cell carcinomas are known to occur in the Ano rectum
      frequently, but are extremely rare in colon especially the right colon.

PMID- 10921225
TI  - Radiation induced sarcoma following treatment of breast cancer.
AB  - The occurrence of radiation induced sarcoma following treatment of breast cancer
      is rare. It has an average latency of ten years and it correlates with the dose
      and technique of radiation. The prognosis is poor due to delay in diagnosis. We
      present a case where a female patient developed a chondrosarcoma of
      sternoclavicular joint 19 years after radiotherapy for breast cancer.

PMID- 10921226
TI  - Pericardial effusion and raised CA-125 level--unusual manifestations of primary
      pulmonary epithelioid hemangioendothelioma.
AB  - Pulmonary epithelioid hemangioendothelioma (PEH) is an uncommon neoplasm. The
      reported case reveals unusual clinical manifestations pericardial effusion and
      raised CA-125 level.

PMID- 10921227
TI  - Metastasis of osteosarcoma to the maxilla--a case report.
AB  - Secondary osteosarcomas of the maxilla/premaxilla are extremely rare. We describe
      a case of a 24-year-old man with a metastasis of osteosarcoma to the premaxilla.
      The patient had undergone hip disarticulation followed by adria based
      chemotherapy for chondroblastic osteosarcoma of the proximal right femur ten
      years ago. The metastatic work up did not show liver or lung metastasis. The
      patient underwent premaxillectomy in February 1999. The histopathology revealed a
      chondroblatic osteosarcoma consistent with metastasis in the clinical setting.
      The patient was disease free at the end of five months.

PMID- 10921228
TI  - Primary carcinoma of fallopian tube--a case study.
AB  - Primary carcinoma of fallopian tube is a rare entity. We report an interesting
      case of primary carcinoma of fallopian tube with contralateral lymph node
      involvement. The clinicopathological findings and its management is presented.

PMID- 10921229
TI  - Krukenberg tumor of ovary with features of mucinous cystadenocarcinoma.
AB  - An unusual case of bilateral Krukenberg tumors having a predominant multicystic
      mucinous component which on gross and microscopic examination resembled a
      mucinous cystadenocarcinoma is presented. It is important to distinguish between
      these two tumors as Krukenberg tumours have a significantly worse prognosis.

PMID- 10921230
TI  - 'Metastatic invasive mole' causing paraplegia.
AB  - We report a rare case of 'metastatic invasive mole' to the spinal cord causing
      paraplegia in a 19-year-old woman. There are no such histologically proven
      reports in the literature since the use of the tumour marker, beta-subunit of
      human chorionic gonadotrophin (beta-HCG) and chemotherapy. We stress the
      importance of considering this rare possibility in young woman with compressive
      myelopathy.

PMID- 10921231
TI  - Primary choriocarcinoma of the ovary. Report of two cases.
AB  - Primary choriocarcinoma of the ovary (PCO) is rare. This can be gestational (GCO)
      or nongestational (NGCO) in origin. It is difficult to differentiate between CGO
      and NGCO. NGCO carries a worse prognosis than GCO. We present two cases of
      metastatic GCO who were treated successfully with combination chemotherapy and
      are alive and disease free at the time of reporting.

PMID- 10921232
TI  - Third party reimbursement for participation in cancer clinical trials: a proposal
      for legislation.

PMID- 10921233
TI  - Funding long-term care: some risk-spreaders create more risks than they cure.

PMID- 10921234
TI  - The application of the Americans with Disabilities Act to the termination of the
      parental rights of individuals with mental disabilities.

PMID- 10921235
TI  - Pesticide toxicity, human subjects, and the Environmental Protection Agency's
      dilemma.

PMID- 10921236
TI  - [A view of behavioral dentistry for comprehensive patient care].

PMID- 10921237
TI  - [Application of enamel matrix derivative for tooth transplantation and
      replantation].
AB  - OBJECTIVE: The purpose of this study was to clarify the effects of enamel matrix
      proteins on the regeneration of periodontal ligament (PDL), during
      transplantation and replantation therapy. MATERIALS AND METHODS: [Exp 1] The
      crown and root apex of extracted dog teeth were removed and the remaining root
      separated longitudinally. Two-thirds of crown-side PDL and cementum were removed.
      Prepared teeth were covered with propyleneglycol alginate (PGA) both with and
      without enamel matrix derivative (EMD) and cultured for 0-14 days. The outgrowth
      length of the tooth was measured and histological observation done. [Exp 2] The
      incisal teeth of adult dogs were extracted and 2/3 of crown side PDL and cementum
      removed. Prepared teeth were treated with PGA containing EMD (EMD group). No
      tooth treatment was done in the control group. Following PGA treatment, teeth
      were replanted. The animals were sacrificed at 2 and 4 weeks after replantation
      and histological observation performed. RESULTS: [Exp 1] The outgrowth length of
      the EMD group was longer than that of the other groups. The width of proliferated
      cell layer on the tooth in the EMD group was thicker. [Exp 2] Ankylosis surface
      of the EMD group was smaller than that of the control group. In the control
      group, the region of ankylosis increased longitudinally. In the EMD group, the
      newly-formed cementum was predominantly cellular cementum. CONCLUSION: The
      results suggested that enamel matrix protein enhance the regeneration of PDL and
      prevent tooth ankylosis in transplantation and replantation therapy.

PMID- 10921239
TI  - [A study on application of multiple jointed contact-type measuring apparatus for
      dental use].
AB  - The measurement of oral maxillofacial region, including dentition and teeth, is
      important information for diagnosis and assessment of treatment in clinical
      dentistry. There are two kinds of the measuring systems, i.e., contact-type
      system and non-contact-type system. The latter mainly has been investigated in
      dentistry, because of its simplicity and quickness for measurement. However,
      since the objects in dentistry have complex shapes with curved surfaces and many
      dead angles, accuracy of values obtained by this system is insufficient for
      clinical use. Even though divided measurement is employed to overcome the
      problems, the increase of measuring element results in deterioration of the
      accuracy. In the present study, the accuracy of a contact-type measuring
      apparatus with 5 pivoting joints was investigated. For the cavity model, the
      depth and the width were measured. For the standardized dental cast which
      consists of three spheres, the diameter of three spheres and the distance of each
      sphere were measured. The values obtained by this apparatus were compared with
      those obtained by the precise 3D-measurement apparatus. The differences were
      insignificant in the cavity model. Significant difference was found in the
      standardized dental cast. However, the difference was very small, and so it is
      negligible in clinical use. By using this apparatus, the form of undercut and
      teeth was reconstructed completely. The results suggested that the multiple
      jointed contact-type measuring apparatus could be applied to the measurement in
      clinical dentistry.

PMID- 10921238
TI  - [Immunosuppressive effect of CTLA-4 blockade and regulatory role of CD8 T cells
      in Th2-mediated humoral immune responses].
AB  - CTLA-4 is a negative regulator for T cell activation and plays an important role
      in down-regulating immune responses and the maintenance of peripheral tolerance.
      The effect of initial treatment with anti-CTLA-4 mAb on murine acute and chronic
      graft-versus-host diseases (GVHD) induced by transfer of either C57BL/6 or BALB/c
      splenocytes into F1 recipient mice has been investigated. The treatment with anti
      CTLA-4 mAb exacerbated the lethality of acute GVHD. Surprisingly, in a chronic
      GVHD model, the similar treatment with anti-CTLA-4 mAb significantly reduced
      serum IgE and IL-4 expression and ameliorated the manifestation of chronic GVHD.
      Analysis of the splenic phenotype revealed that blockade of CTLA-4 greatly
      enhanced donor T cell expansion, especially within the CD8 subset. The transfer
      of CD8-depleted splenocytes did not exhibit the inhibitory effect by the anti
      CTLA-4 mAb treatment, suggesting that CD8 T cells are required for an inhibitory
      effect of anti-CTLA-4 mAb. The regulatory roles of CD8 T cells and CTLA-4 pathway
      blockade in Th2-mediated immune responses were further confirmed by in vitro
      experiments using BALB/c T cell responses to allo-antigen. The immunosuppressive
      effect of CTLA-4 blockade and the regulatory function of CD8 T cells in Th2
      mediated immune responses were demonstrated.

PMID- 10921240
TI  - [Study on improvement of adaptation for inlay made by dental CAD/CAM CEREC 2
      system].
AB  - The purpose of this study was to evaluate the effect of changes in the tapering
      angle of inlay casting, adhesive gap and cavosurface margin on the cavity wall
      adaptability of the inlay made by the dental CAD/CAM CEREC 2 system. Designed
      inlay castings were fabricated at three different tapering angles: 0, 3, and 6
      degrees. Adhesive gap of 0, -50, -100 microns and adhesive gap of 0 micron
      combined with the adjustment of cavosurface margin at 2 and 4 pixels were also
      evaluated. The difference between the direct method with powder and the indirect
      method without powder were compared under all conditions. The gap between the
      castings and cavity walls were assessed under a telescopic microscope. Internal
      adaptation of castings was determined to measure the cement thickness on the
      surfaces sectioned in the central portion of the cavity. It was found that inlays
      fabricated at 3 or 6 degree taper exhibited less gap at the side wall of the
      cavity than those without taper. The indirect method without powder also showed
      less gap when compared with the direct method with powder. Marginal gap and the
      cement width at the side wall of the cavity were reduced when the adhesive gap
      was modified to -50 or -100 microns or the cavosurface margin was adjusted at 2
      or 4 pixels in the outer margin. The results suggested that the indirect method
      with the taper of 3 or 6 degrees of inlay casting, or with adjustment of adhesive
      gap to -50 microns provided the best adaptability between the castings and cavity
      walls.

PMID- 10921241
TI  - [Expression of cyclin E in postmitotic cells in the central nervous system].
AB  - Cyclin E, a member of G1 cyclins, is expressed specifically at the G1 to S phase
      in proliferating cells and promotes the entry into S phase by binding and
      activating a specific cyclin-dependent kinase, cdk2. To investigate the
      regulatory mechanisms of the cell cycle in the developing central nervous system
      (CNS), this study was conducted to analyze expression of cyclin E and other G1
      cyclins/cdks in the developing and adult mice and rats. Western blotting and in
      situ hybridization indicate that both mRNA and protein of cyclin E are expressed
      in the developing CNS, and are also detected in adulthood when no expression of
      other G1 cyclins and cdks is observed. Immunohistochemical analysis reveals that,
      during development of the cerebral cortex, cyclin E protein is expressed not only
      in proliferating regions but also in differentiating regions where cells are
      mitotically negative, and that subcellular localization of cyclin E protein
      changes from the nucleus to the cytoplasm during postnatal development of CNS.
      Cyclin E forms a complex with cdk5 which is activated by a neuron-specific
      regulatory subunit, p35, and cyclin E/cdk5 complex was detected mainly in the
      cytoplasm, although no cyclin E-associated kinase activity was detected in the
      adult CNS. These results indicate that cyclin E is expressed in terminally
      differentiated neurons which are already withdrawn from the cell cycle, and
      suggest a novel role for cyclin E in postmitotic neurons in the CNS in addition
      to its role in cell cycle regulation in proliferating neuroblasts.

PMID- 10921242
TI  - [Functional analysis of apoptosis signal-regulating kinase 1 (ASK 1)-binding
      proteins].
AB  - Tumor necrosis factor (TNF) and interleukin-1 (IL-1) are pleiotropic cytokines
      that activate two transcription factors, Activator Protein-1 (AP-1) and Nuclear
      Factor-kappa B (NF-kappa B). Apoptosis signal-regulating kinase 1 (ASK 1) is a
      mitogen-activated protein (MAP) kinase kinase kinase (MAPKKK) that is activated
      by TNF and IL-1, and stimulates c-Jun N-terminal kinase (JNK also known as SAPK;
      stress-activated protein kinase) and p38 activation. Through genetic screening
      for ASK 1-binding proteins, Transforming Growth Factor beta (TGF-beta)-activated
      kinase (TAK 1), another MAPKKK family protein, was identified. Here we report
      that ASK 1 binds to TAK 1 and dissociates TAK 1 from TNF receptor-associated
      factor 6 (TRAF 6), and inhibits TAK 1- and TRAF 6-, but not NF-kappa B-inducing
      kinase (NIK)-induced NF-kappa B activation.

PMID- 10921243
TI  - [Correlation of DNA copy number changes to malignancy in oral squamous cell
      carcinomas by comparative genomic hybridization].
AB  - To compare clinical and histopathological findings to tumor DNA copy number
      changes, comparative genomic hybridization (CGH) was performed on 18 primary oral
      squamous cell carcinomas. Copy number increases were most frequently observed on
      8q, 3q, 13q, 11p, and 11q, while copy number decreases most frequently on 10q,
      1p, 18q, 9p, and 19q. Copy number changes in relationship to WHO grading were
      examined with the result that DNA copy number increase on chromosome 6p23-25 was
      characteristically observed in the groups of Grade II and Grade III, and DNA copy
      number decreases on chromosomes 9p21 and 11p11-13 were observed in the same
      groups. Furthermore, comparison of DNA copy number changes to TNM classification
      indicated that the decreases on chromosomes 1p36 and 10q25-26 might be related to
      tumor progression. Moreover, the relationship of DNA amplification or deletion to
      metastasis was investigated. It was found that the majority of the metastasis
      positive tumors showed increases on 3q26 and 17q12-21 and showed decreases on
      chromosome 18q21. The data suggested that these DNA copy number changes on each
      chromosome in the three categories might be associated with tumor cell
      differentiation, tumor size, and lymph node metastasis.

PMID- 10921244
TI  - [Interchangeability of resin composites and bonding agents based on bis-GMA or
      UDMA].
AB  - Recently, dentin bonding systems have been released separately from the resin
      composites, because the adhesive systems have been quickly improved. Since the
      merit of each material should be effectively utilized for each clinical case, the
      bonding systems and resin composites produced by different manufacturers may be
      combined according to the clinical purpose. The current restorative resins are
      basically categorized into two groups according to the main resin monomer, bis
      GMA or UDMA resins. The purpose of this study was to evaluate the
      interchangeability between the bonding systems and resin composites, which were
      made by different manufacturers. Two bonding systems and five resin composites
      based on bis-GMA or UDMA were used in this study. The evaluation was performed by
      the tensile bond strength, fracture modes, and SEM observation, using the dentin
      surface of freshly-extracted bovine teeth. The highest bond strength (19.2 MPa)
      was shown by the combination of LBII sigma and AP-X. The bond strengths of nine
      other combinations were not statistically different (p > 0.05). There were many
      cohesive failures in dentin or resin composite, using all combinations. From the
      results, it was concluded that the interchangeability of the resin composites and
      bonding systems should be clinically acceptable.

PMID- 10921245
TI  - [Dental treatment for the handicapped by a combination of public community,
      dental association and university hospital--a system of Suginoki Dental Clinic].
AB  - Suginoki Dental Clinic, which is managed by Suginami Dental Association,
      financially supported by Suginami City, and technically assisted by the
      University Hospital, Tokyo Medical and Dental University, was established for
      dental treatment of handicapped persons living in Suginami City, Tokyo who are
      difficult to be treated by private practitioners. It has one full-time dentist,
      12 part-time dentists, two dental hygienists, one nurse, and one clerk; one of
      the part-time dentists practices twice a week there. Since December 1994, 406
      patients visited the clinic and the total cases was 9,273 in December 1999; 99
      cases were mentally retarded, 36 autism, and 30 epileptic patients in the younger
      group; and 65 cases were cerebrovascular disease and 27 cardiac malfunction
      patients in the older group. Almost all the patients needed special care such as
      monitoring, intravenous sedation, nitrous oxide sedation, and general anesthesia.
      Four cases underwent general anesthesia, and no complication was seen among the
      cases. It was concluded that the clinic has been successful due to a good
      relationship among the Dental Association, Suginami City, and the dental
      hospital.

PMID- 10921246
TI  - [A long-term follow-up case of multiple impacted teeth associated with large
      follicular cyst in maxilla].
AB  - Longitudinal record of a case of multiple impacted teeth associated with large
      follicular cyst in the right maxilla was presented. The patient was an 8-year-10
      month-old girl whose chief complaint was delayed eruption of the right upper
      incisor. Clinical examination revealed a large follicular cyst in the right
      maxillary sinus, which greatly displaced teeth germs. Marsupialization followed
      by orthodontic extrusion successfully brought unerupted teeth into their
      positions. Greatly displaced upper right canine, which was as high as the floor
      of the orbit, erupted spontaneously after reduction of the lesion. During the
      subsequent years, the patient developed crowded dentition and reduced overbite,
      which needed additional orthodontic treatment with extraction of premolars. The
      patient was 26-years 8-months old upon completion of treatment. The surgical,
      orthodontic, and periodontological aspects of the case were reexamined.
      Marsupialization of dentigerous cysts can preserve impacted teeth, however, the
      outcome might be affected by several factors such as overall growth of facial
      bones.

PMID- 10921247
TI  - [The history of the development of sports medicine and therapeutic physical
      exercise in Ukraine].
AB  - The article focuses on stages of the history of development of sports medicine
      and remedial gymnastics in Ukraine. Shown in the article is a high level
      development of physical culture and its medical maintenance in Ukraine in the
      beginning of the 20th century. A valuable contribution to the development of
      remedial gymnastics and sports medicine was made, among others, by Professors O.
      V. Pocharovska, V. T. Stovbun, I. P. Kalistov, Yu. A. Chiyak, H. L. Apanasenko,
      S. A. Dushanin, V. V. Klapchuk, V. F. Shapovalova. The role sports medicine has
      in enhancement of capacity for work and maintenance of health of sportsmen is
      shown.

PMID- 10921248
TI  - [The irritable bowel syndrome: the current state of the problem].
AB  - The article presents current data on the irritable colon syndrome and reviews
      information about etiology, pathogenesis, classification, clinical picture of the
      disorder. Principles of treatment of colonic functional disorders are fully
      detailed. Results are submitted of treatment of 40 patients presenting with
      unstable colon. High efficacy and safety are shown of a new drug decitel that can
      be recommended as treatment of patients with unstable colon both as monotherapy
      and combined with other drugs.

PMID- 10921249
TI  - [The comparative characteristics of the renal protective properties of
      angiotensin-converting enzyme inhibitors and calcium channel blockers].

PMID- 10921250
TI  - [The use of calcitonin in treating osteoporosis].

PMID- 10921251
TI  - [The adaptive potentials of those who worked in the cleanup of the aftermath of
      the accident at the Chernobyl Atomic Electric Power Station under the influence
      of different treatment methods].
AB  - A comprehensive evaluation was done in 162 patients-liquidators of the Chernobyl
      accident. Of these, 80 percent were diagnosed as having stage I and II
      dyscirculatory encephalopathy (DE), 20 percent were in stage III. It is shown
      that DE progression is caused by great strain on and breakdown of autoregulatory
      mechanisms of different biological systems (vascular, central nervous and
      vegetative, hormonal), and of central regulatory mechanisms as well. Under
      certain conditions there may occur their breakdown, with syncopal states, crises,
      and even insults developing in its wake. Treatment and rehabilitation of DE
      liquidators with pyracetam, vinpocetine, cerebrolysine with magne B6, and
      phytosorbents (spirulina, quercitrol, and vitapectine) lead to reconditioning of
      central and autoregulatory compensatory-and-adaptive mechanisms, long-lasting
      remission, provide complication prophylaxis and promote work activity.

PMID- 10921252
TI  - [The state of the dental hard tissues in persons under the influence of ionizing
      radiation (based on the data from infrared spectroscopy)].
AB  - A total of 27 teeth were examined in those subjects having been exposed to
      ionizing radiation in doses between 0.5 and 2.0 Gy, together with ten teeth of
      essentially healthy individuals. The enamel, dentine and cement mineral and
      protein contents were studied versus control with the aid of infrared
      spectroscopy techniques. It has been ascertained that in the teeth of patients
      presenting with dose loads there take place changes in the organic matrix. Amide
      I: amide II ratio tends to diminish toward contribution of Amide I. The mineral
      composition of the enamel reveals practically no changes under exposure to
      radiation. The dentine and cement display clear-cut changes in the mineral
      component. There appear absorption bands that belong to more soluble forms of
      calcium phosphate, which fact suggests an active destructive process in
      underlying hard tissues of the teeth, that gets intensified under exposure to
      ionizing radiation.

PMID- 10921254
TI  - [Changes in lipid peroxidation in patients with heart failure combined with
      symptomatic arterial hypertension].
AB  - Data from published literature are submitted together with findings from the
      author's studies on the condition of lipid peroxidation (LPO) and antioxidant
      system (AOS) in those patients with heart failure (HF) complicated by symptomatic
      arterial hypertension against the background of chronic pyelonephritis. All
      groups patients demonstrated activation of LPO processes and depression of AOS.
      The use of thiotriazoline and adaptogens was found to return LPO processes back
      to normal.

PMID- 10921253
TI  - [The determination of the water-migration index of the harmfulness of a complex
      of pollutants: the anionic surface-active substance PO-1D, hexachlorocyclohexane
      and ammonium nitrate].
AB  - Some aspects are studied of migration of the complex of priority soil
      contaminants anionic detergents, hexachlorocyclohexane (HCCH) and nitrogenous
      fertilizers. The anionic surface-active substance [symbol: see text] favours
      migratory properties of nitrates, HCCH. Permissible load of anionic surface
      active substances on the black earth soil that comes up to 17 kg/ha is validated.

PMID- 10921255
TI  - [The effect of alpha-1 adrenergic blockade on the clinical course, immune status
      and blood plasma lipid spectrum in patients with ischemic heart disease].
AB  - Results are submitted of investigations designed to study effects of prazosine on
      the clinical course, immune and lipid spectrum of blood plasma in IHD patients
      with functional class I-II middle-aged and elderly-onset exertional angina.
      Efficiency of prazosine monotherapy was recordable in all FC I-II effort angina
      patients 30 to 50 years old, which fact was manifested by a decline in the number
      of angina attacks over the 24-hour period, number and duration of both pain and
      symptom-free myocardial ischemia, improvement in physical load tolerance. Also
      recordable in all patients was a positive effect of the drug on blood plasma
      lipid spectrum and certain immunological indices.

PMID- 10921256
TI  - [The effect of angiotensin-II receptor antagonists on the vasoconstriction
      mechanisms in chronic heart failure].
AB  - Overall thirty-two patients with chronic heart failure (CHF) II-IV FC according
      to NYHA classification were studied for effects of irbesartan, an antagonist of
      receptors to angiotensine II on mechanisms of vasoconstriction. Noted as a result
      of the treatment conducted was a significant reduction in the content of
      vasoconstrictors of angiotensin II, vasopressin, and epinephrine as well as a
      tendency toward decrease in values for thromboxane A2 and adrenaline.
      Vasoconstrictor factors were found to have an important part in vascular control
      in realization of efficacy of irbesartan, an antagonist of receptors to
      angiotensin II, in CHF patients.

PMID- 10921257
TI  - [The diagnostic significance of the indices of oxygen-dependent neutrophil
      metabolism in rheumatism patients with a background of leukopenia].
AB  - Results are submitted of investigations designed to study parameters
      characterizing the peripheral blood neutrophil functional activity in leukopenias
      accompanying the course of rheumatism. Neutrophils were proved to be defective,
      their disturbed functional activity being manifested by the decrement of their
      ability to restore the NBT-test. There has been noted an inadequate augmentation
      of the metabolic activity following neutrophil stimulation as compared to results
      in healthy subjects. Of practical significance in the above investigations is
      screening of patients presenting with low values for the functional reserve of
      neutrophils as a threat to the early prediction of the course of pyo-inflammatory
      complications. It is suggested that a spontaneous NBT-test be used in the
      differential diagnosis of bacterial and non-bacterial complications while a
      stimulated NBT-test is believed to be helpful in identifying neutrophil
      dysfunction when results of a spontaneous NBT-test are at variance with clinical
      findings.

PMID- 10921258
TI  - [The function of the liver mono-oxygenase system in a non-coronarogenic lesion of
      the heart muscle in an experiment].
AB  - The functional state was studied of the monooxygenase system in the liver in the
      time-related progression of izardine-induced myocarditis (IM) and allergic
      myocarditis (AM) in rats. In IM, the activity of monooxygenase enzymes (ME) was
      found to have gotten increased against the background of a decrease in the
      content of microsomal cytochromes, which event is believed to be secondary to a
      direct effect of izardine on the liver. In AM, a decline in ME activity appeared
      to correlate with a decrease in the content of microsomal cytochromes. This
      suggests a direct impact of cardiac pathology on the liver.

PMID- 10921259
TI  - [The prognostic importance of rheopulmonography in the diagnosis of
      thromboembolic complications].
AB  - A possibility was analyzed of use of rheopulmonography in the diagnosis of
      thromboembolic complications. Studies were made as exemplified by examination of
      patients operated on for abdominal hemorrhages. As a result of multiparametric
      statistical processing of the analysis results two groups were identified of
      indices for the state of pulmonary bloodflow and ventilation, effectiveness of
      alveolar-arterial gas transfer. In the first group, the values were within the
      relatively normal range, the second group being patients with
      microthromboembolism of the pulmonary artery. The use of pharmacological methods
      for the prophylaxis administration was seen to result in lower probability of
      pneumonia origination in the examined patients. Zonal rheopulmonography is
      believed to allow some judgement about the probability of the thromboembolic
      complications development and control over the efficiency of methods for their
      prevention.

PMID- 10921260
TI  - [The determination of sialic acids in the lymphocytes of multiple sclerosis
      patients].
AB  - Overall, twenty patients with multiple sclerosis of varying degree severity, its
      clinical course being dissimilar among patients, were studied for lymphocyte
      concentration of sialic acids. It has been ascertained that multiple sclerosis
      provokes augmentation of lymphocyte content of sialic acids, with greater
      increase being noted in patients with 1 to 3 and 6 to 9 scores on the Kurtzke's
      scale and in women as well.

PMID- 10921261
TI  - [The biomechanical basis for the number of blocking screws in the intramedullary
      metal-polymer osteosynthesis of comminuted longitudinally unstable fractures of
      the femoral diaphysis].
AB  - A technique is submitted for finding the minimum number of blocking screws in
      carrying out a blocking intramedullary metallopolymeric osteosynthesis of
      comminuted longitudinal unstable fractures of the femoral diaphysis. It has been
      shown that to ensure stability of the system of injury "bone-clamp" under
      conditions of dynamic loads it is necessary that four blocking screws be passed
      in age groups I and II, with six blocking screws being used in age group III.

PMID- 10921262
TI  - [The side effects of angiotensin-converting enzyme inhibitors in the treatment of
      arterial hypertension].
AB  - Wide use of angiotensin-converting enzyme (ACE) inhibitors in clinical settings
      is to a certain extent associated with a small number of side effects developing
      after taking the above medicines. The most prominent ill effects of ACE
      inhibitors include hypotension, acute renal impairement in those patients
      presenting with stenosis of the renal artery or manifest circulatory
      insufficiency, hyperpotassemia developing because of taking potassium-storing
      diuretics; cough, Quincke's edema, headache, syncope, orthostatic hypotension,
      nausea, diarrhea, skin eruption.

PMID- 10921263
TI  - [The evaluation of the efficacy of the hydro- and balneo-laser therapy of
      patients with arterial hypertension].
AB  - The method of hydro- and balneo-laser therapy is highly effective in optimization
      of adaptation, improvement in physical and cardiac performance. However
      examination of data in the comparative aspect showed that balneo-laser therapy is
      a more effective treatment option compared to hydro-laser therapy.

PMID- 10921264
TI  - [The basic stages in the diagnosis and treatment of necrotic forms of acute
      pancreatitis].
AB  - An analysis has been performed of results of treatment of 2740 patients with
      acute destructive pancreatitis over the period between 1973 and the present time,
      together with those from published literature. Based on the above analysis, an
      algorithm has been developed to be used in diagnosis and treatment of necrotic
      forms of pancreatitis, that permitted reducing the postoperative mortality
      associated with the pathology under consideration from 31.3% to 14.2-14.71%, the
      general case fatality rate coming up to as low as 6.15% over the last ten years.

PMID- 10921265
TI  - [The surgical treatment of a postoperative ventral hernia occurring at the site
      of a McBurney approach].
AB  - Results were studied of surgical treatment of 456 patients presenting with
      postoperative ventral hernias (POVH) in different sites of the body. In 50 (11%)
      patients POVH came forth after McBurney approach. The patients' age ranged
      between 41 to 73 years. Hernioplasty was done taking into account the size of the
      hernia and resistance of tissues that were sutured in layers, with resultant
      aponeurosis duplication having been formed, and in some cases with simultaneous
      reinforcement thereof with an autodermal strip and patch. The patients had come
      to be examined postoperatively in a 1-to-10-yr follow-up. Recurrence of hernia
      occurred in 6 (12%) in the wake of hernioplasty as recommended by Sapezhko,
      suturing of the hernia defect in layers with formation of aponeurosis duplication
      and immobilization of the suture line, with n = 3, 2, and 1 respectively.

PMID- 10921266
TI  - [Changes in the vascular wall in a combination of hypercholesterolemia and
      posttraumatic regeneration of the endothelium].
AB  - Proceeding from our notions about proatherogenic properties of
      hypercholesterinemia and capability of injurious effects on the vascular wall to
      stimulate the process, sequelae were studied of a combined effect of the above
      factors on the endothelial monolayer of the aorta in an animal experiment
      (rabbits, n = 17). Used in the study were AgNO3 impregnation, electron
      microscopy, histochemistry, and morphometry. It has been ascertained that
      association of chronic hypercholesterinemia with local mechanical damage to the
      vascular endothelium tends to change its morphofunctional properties to a greater
      degree than in differentiated action of each of them promoting significantly the
      development of atherosclerosis in differentiated action of each of them.

PMID- 10921267
TI  - [An analysis of the immunity indices of patients with iron-deficiency anemia].
AB  - The article gives an analysis of certain parameters characterizing cell-mediated
      and humoral immunity in patients with iron deficiency anemia (IDA). At the onset
      of treatment the immunologic vigor in IDA patients was characterized by a
      reduction in the relative number of T-lymphocytes and their helper subpopulation
      while after the treatments administered there was a rise in the relative numbers
      of B-lymphocytes against the background of presence of B-helper deficiency with
      the T-lymphocyte counts having returned to normal. Changes revealed in the T
      lymphocyte system in IDA patients may suggest formation of early secondary
      immunodeficiency.

PMID- 10921268
TI  - [Glomerulonephritis in the aspect of patient self-assessment].
AB  - It is shown that organization of dispensary follow-up of patients with
      glomerulonephritis fails to ensure completeness of records-taking and control of
      the disease course in a timely fashion. The following items were found to
      influence negatively the quality of specialized medical aid: too late applying of
      patients for medical advice, non-adherence to the physician's prescriptions and
      self-curing, which fact is not infrequently related to the patients' inadequate
      material gains and lack of care in respect of their own health. This warrants
      heightening of medical-and-educational activities. Risk groups to be targeted for
      special care include women (in spite of greater disability rates among male
      subjects), persons aged less than 20 and those beyond 40 years old, those persons
      that have not completed high education, and those residing in rural areas.

PMID- 10921269
TI  - [The characteristics of improving the prevention of male infertility].
AB  - The author analyzes major shortcomings in the administration of male infertility
      prophylaxis. An association has been found out between the late onset of surgical
      correction of congenital abnormalities of the testis and spermatic cord and
      displeasing results of treatment. An outline is submitted of prophylactic
      management of children presenting with this pathology. Its implementation into
      the practical activities of outpatient physicians will, we believe, help in
      achieving better results with treatment of children having testis malformation
      and in perfecting the administration of male sterility prophylaxis.

PMID- 10921270
TI  - [The validation of the expediency of using pimozide in treating the hypomania
      syndrome of alcoholic origin].
AB  - In a clinical and psychopathological study of alcohol-dependent patients
      presenting with emotional disturbances and hypomaniac syndrome, expediency was
      shown of use of a neuroleptic drug preparation pimozide in the treatment of
      hypomaniac syndrome of alcohol genesis.

PMID- 10921271
TI  - [The phenomenon of the skin-optical perception of color and images on an
      "internal visual screen"].

PMID- 10921272
TI  - [The prevalence of ischemic heart disease and the characteristics of sudden
      cardiac death in miners of the Donets Basin coal mines].
AB  - Prevalence of ischemic heart disease (IHD) and of general population risk factors
      was studied on the basis of results of the epidemiological survey among miners (n
      = 6500) working in coal mines of Donbass with different mining and geological
      conditions and mining and technical characteristics. In the above series, there
      prevailed exertional angina and an arrhythmia form of IHD in which the pain
      syndrome was absent or was of atypical character. Recordable in the miners was an
      age-associated increase in IHD prevalence. There was also a relatedness of this
      parameter to the length of service in underground conditions. Direct correlation
      between the underground service duration and IHD rates was ascertained in all age
      groups. In 56 percent of cases unexpected cardiac death occurred at job or on the
      worker's way home, which event was in 63 percent of cases related to hard
      strenuous work, performing labour-consuming operations at high temperature.
      Furthermore, in 80 percent of cases the above events were preceded by
      psychoemotional overstrain.

PMID- 10921273
TI  - [The prognosis of peptic ulcer in workers in a mining and smelting complex].
AB  - The finger and palmar patterns were studied in miners suffering from peptic ulcer
      and in healthy subjects. The revealed complex of 26 dermatoglyphic indicators
      permit the prognostication of peptic ulcer, which fact promotes efficiency of
      measures designed to prevent the disorder.

PMID- 10921274
TI  - [Forlax in the treatment of chronic constipation of different origins].
AB  - The greatest benefit from forlax occurs in patients with constipation of various
      etiology. The highest effect was recordable in those patients with functional
      pathology of the intestinal tract who experienced increased frequency of their
      stools and alleviation of clinical manifestations of the illness to the greatest
      degree. In patients with decompensated cirrhosis normalization of stool was
      accompanied by a significant improvement in general condition and what is more,
      clinical manifestations of portal-systemic encephalopathy tended to be less
      pronounced. Relatively lower benefit from treatment with forlax occurred in those
      patients presenting with an appreciable decline in propulsive activity of the
      intestines against the background of severe diabetes mellitus. The therapy of
      these patients was supplemented with prokinetics in the belief that this measure
      will help in achieving stable normalization of stool.

PMID- 10921276
TI  - [The experience of the effective use of computer technology in the management of
      a medical institution].
AB  - Submitted in the paper are some general results of a many-years' standing
      experience gained with the use of computer engineering and computer methods in
      practical activities of a medical institution, concerning in particular
      organization matters, practical aspects of programme, technical, and cadre
      maintenance. Advantages are shown together with some results of effectiveness of
      employment of computer engineering in the therapeutic-and-diagnostic process and
      cultural aspect of medical activities.

PMID- 10921275
TI  - [The current concept of the preventive activities of medical institutions in the
      rural public health link (a review of the literature)].

PMID- 10921277
TI  - [The place of hypertension in the structure of the morbidity of the circulatory
      system organs among the adult population of L'viv Province].
AB  - The analysis of the Lviv Province adult population case rates over 1994-1996 in
      accordance with indices for prevalence of morbidity, general morbidity, primary
      invalidism and mortality shows that disorders of the circulation organs pose a
      problem of major social significance and are supposed to be dealt with very
      thoughtfully in order that it may be possible to prevent their origination and
      progression. Arterial hypertension in the VIIIth class of disorders is the most
      common disease and major risk factor of other illnesses origination and
      development. All this warrants, in the first place, doubled prophylactic work as
      to early detection of patients with essential hypertension and complex solution
      of this problem on the part of the state that faces it.

PMID- 10921279
TI  - [In Process Citation]

PMID- 10921278
TI  - [Patients with sexually transmitted diseases and the physicians delivering care
      as elements in the medical services market].
AB  - The article focuses on the cost of medical services delivered to patients
      presenting with infections transmitted by direct contact as by sexual intercourse
      (STI). Both physicians' and patients' incomes were studied as were patterns of
      expenditure in everyday life. The rough level of expenditure on the delivery of
      health care from the standpoint of physicians is estimated, the patients
      displaying readiness to bear the above expenses.

PMID- 10921280
TI  - [Cigarette smoke-induced acute airway impairment].
AB  - Cigarette smoking has been implicated in many pulmonary disorders, including
      chronic bronchitis and chronic obstructive lung disease. Cigarette smoking is
      associated with increased airway responsiveness. Acute exposure to cigarette
      smoke increases airway responsiveness in a dose-dependent manner. A superoxide is
      involved in airway hyper-responsiveness induced by cigarette smoke, perhaps by
      direct toxic action. Cigarette smokers have increased numbers of neutrophils
      present in their lower respiratory tract. Acute exposure to cigarette smoke
      initiates a superoxide-dependent mechanism that, through NF-kappa B activation
      and IL-8 expression, induces infiltration of neutrophils into the airways in
      vivo. The alveolar macrophage is one potential source of NF-kappa B activation
      and IL-8 production after acute exposure to cigarette smoke. Manipulation of NF
      kappa B by antioxidants in vivo may be useful in limiting biologic processes such
      as pro-inflammatory cytokine production, which may lead to neutrophil
      accumulation in the lung.

PMID- 10921281
TI  - [Evaluation of lung lobar ventilation dynamics with magnetic resonance imaging: a
      comparison of interstitial pneumonia patients with normal subjects].
AB  - Magnetic resonance imaging (MRI) was utilized to study lung lobar dynamic
      ventilation in 11 patients with interstitial pneumonia (IP) and 10 non-smoking
      men. The IP patients included 7 with interstitial lung disease associated with
      collagen vascular disease, 3 with idiopathic interstitial pneumonia, and 1 with
      lung cancer who was excluded from statistical analysis. We calculated lung lobar
      volumes in each phase from each dynamic image and constructed time-volume
      curves(TVCs). Lung lobar volume rates(%), fluctuation rates(%), lobar fluctuation
      rate/total lung fluctuation rate (%), and time lag (sec.) for the IP patients and
      normal subjects were calculated and compared. In the former, the mean volume rate
      for the right upper lobe was larger (p < 0.01) than that in normal subjects. The
      mean volume rate for the left lower lobe in the IP patients was smaller(p < 0.01)
      than that in the normal subjects. In IP patients, peak TVC for the right middle
      lobe appeared later (p < 0.01) than that in normal subjects. Although the
      fluctuation rates and fluctuation rate/total lung fluctuation rate for the lower
      lobes tended to be higher than those for the upper and middle lobes in normal
      subjects, this tendency was not distinct in IP patients. The quantitative
      evaluation of pulmonary ventilation dynamics with MRI may be a useful noninvasive
      technique for the assessment of lung lobar ventilation in patients with IP.

PMID- 10921282
TI  - [Therapeutic bronchoscopy for stenotic lesions of central airway].
AB  - We retrospectively studied 26 patients with stenotic lesions of the central
      airway who had undergone bronchoscopic treatment. Thirteen of the patients had
      malignant tumors, and 13 had benign lesions (1 with post-tracheostomy difficulty
      in tube retrieval, 2 with bronchial obstruction due to granulation after
      bronchoplasty, 1 with bronchial stenosis due to granulation after pulmonary
      lobectomy, 7 with endobronchial foreign bodies, and 2 with hemoptysis). The
      patients ranged from 5 to 88 years of age with an average of 59.7 years. As a
      rule, bronchoscopic treatment was performed with endotracheal intubation up to
      1993, and with laryngeal mask placement in 1994 and thereafter. Of the 26
      eligible patients, 24 (92%) experienced good or excellent outcomes. Emergency
      bronchoscopy may be useful in treating a variety of emergency airway conditions.
      Use of a laryngeal mask may benefit emergency patients, including infants and
      children requiring a secure airway without complications.

PMID- 10921283
TI  - [A comparative study of computed tomographic techniques for the detection of
      emphysema in middle-aged and older patient populations].
AB  - Helical-scan computed tomography (CT) is now widely utilized as a mass screening
      procedure for lung cancer. By adding 3 slices of high-resolution CT (HRCT) to the
      standard screening procedure, we were able to compare the efficacy of helical
      scan CT and HRCT in detecting pulmonary emphysema. Additionally, the prevalence
      of emphysema detected by HRCT was examined as a function of patient age and
      smoking history. The subjects (106 men and 28 women) were all community-based
      middle-aged and older volunteers who participated in a mass lung cancer screening
      program. Based on visual assessments of the CT films, emphysema was detected in
      29 subjects (22%) by HRCT, but in only 4 (3%) by helical-scan CT. Although the
      prevalence of emphysema was higher among subjects with a higher smoking index, no
      correlations with age were observed. We concluded that the efficacy of helical
      scan CT in detecting pulmonary emphysema can be significantly improved with the
      inclusion of 3 slices of HRCT, and confirmed that cigarette smoking is linked to
      the development of pulmonary emphysema.

PMID- 10921284
TI  - [A study of the difficulty of identifying normal intrathoracic structures on CRT
      images: a search for the optimal luminescence ratio].
AB  - This study was concerned with 2 issues: whether there are any normal
      intrathoracic anatomical structures that are relatively more difficult to
      identify on CRT (cathode-ray tube) monitor images, and if so, what their features
      are. Four physicians examined 7 intrathoracic anatomical structures on 50 chest
      roentgenograms that were displayed on CRT monitors and as conventional X-ray
      films on a light box. They categorized the visibility of each structure into 5
      grades. The 7 structures were the spinal process behind the trachea, right margin
      of trachea, right main bronchus, left main bronchus, vascular shadow behind right
      diaphragm, vascular shadow behind cardiac shadow, and right margin of descending
      aorta. Luminescence ratios were calculated as the ratio of the density of a given
      viewpoint relative to adjacent areas on the images. We also examined the
      correlations between luminescence ratio and degree of difficulty in interpreting
      CRT images at a variety of selected luminescence ratios. Although the spinal
      process and trachea were easy to identify on CRT images as well as conventional
      films, other structures were difficult to recognize on CRT images. The
      luminescence ratio of each structure was higher on conventional film, and
      relatively low for those structures that were difficult to identify on CRT
      images. Each structure became gradually easier to identify with increasing
      luminescence ratios, up to a value of 1.07 maximum. However, this improvement in
      visibility leveled off beyond 1.07. We concluded that the luminescence ratio
      should be maintained at more than 1.07 to facilitate optimal identification of
      overlapping anatomical structures on CRT images.

PMID- 10921285
TI  - [Erdheim-Chester disease presenting with pulmonary lesion].
AB  - A 49-year-old man first visited our hospital in 1991 for further examination of
      abnormal pulmonary shadows. A chest radiograph and computed tomographic (CT) scan
      showed diffuse reticular shadows in both lung fields. The findings from a
      transbronchial lung biopsy specimen were not conclusive. Although there was
      little change in the abnormal pulmonary shadows, the patient's lung functions
      gradually deteriorated, indicating an obstructive defect. The patient was
      admitted in 1998 with the chief complaint of increasing dyspnea on exertion. A
      thoracoscopic lung biopsy specimen revealed proliferation of histiocytes with
      fibrosis in the pleura and perivascular interstitium. Immunohistochemically, the
      histiocytic cells were CD68-positive, alpha 1-antichymotripsin-positive, S100
      protein-negative, and CD1a-negative. A bone scintigram and magnetic resonance
      images showed symmetrical diametaphyseal bone lesions in the distal femurs and
      the proximal tibiae; however, the epiphyses were spared. These findings were
      consistent with Erdheim-Chester disease. This is the first reported case of
      Erdheim-Chester disease with pulmonary involvement in Japan.

PMID- 10921286
TI  - [Levofloxacin-induced eosinophilic pneumonia complicated by bronchial asthma].
AB  - A 76-year-old woman who had complained of cough and productive sputum since mid
      January, 1999, was admitted to our hospital with fever and dyspnea on February 4,
      1999. She had been treated with levofloxacin at an outpatient clinic. On
      admission, she had orthopnea, and auscultation revealed coarse crackles and
      wheeze in the bilateral lung fields. Chest x-ray and CT films showed non
      segmental infiltration in bilateral lung fields. Laboratory data revealed
      eosinophilia in peripheral blood (= 24%) and sputum (= 10%), airflow limitation,
      hypoxemia (PaO2: 46 Torr), and increased airway responsiveness to methacholine
      (Dmin: 0.127 units). A bronchoalveolar lavage (BAL) fluid showed increased total
      cells and a 55% increase in eosinophils, and CD4/CD8 ratio was decreased to 0.8.
      In addition, IL-5 was increased in BAL fluid. Transbronchial lung biopsy
      specimens revealed infiltrations of eosinophils in the alveolar and interstitial
      compartments. Histological features of the bronchial biopsy specimens included
      increased eosinophils in the submucosa and goblet cell metaplasia. The woman was
      diagnosed with eosinophilic pneumonia complicated by bronchial asthma. She was
      given theophylline, pranlukast hydrate, and an inhaled beta 2 receptor agonist
      (procaterol hydrochloride), and pre-admission drugs including Levofloxacin were
      discontinued. Her symptoms were improved, peak expiratory flow rate and PaO2
      increased, airway responsiveness to methacholine decreased (Dmin: 0.615 units),
      and radiographic abnormalities disappeared without steroid therapy. A leukocyte
      migration test for levofloxacin was weakly positive. An environmental provocation
      test in the patient's home gave negative results. A challenge test for
      levofloxacin was not performed due to a lack of informed consent. Based on these
      findings, we diagnosed this case as levofloxacin-induced lung injury manifesting
      as eosinophilic pneumonia complicated by bronchial asthma. Levofloxacin should be
      added to the list of agents that can produce eosinophilic pneumonia.

PMID- 10921287
TI  - [Anaplastic thyroid carcinoma with lung metastasis producing CA 19-9 and GM-CSF].
AB  - A 68-year-old Japanese woman was admitted to our hospital because of hoarseness,
      dysphagia and a mass on the right side of her neck. Chest radiographs showed
      multiple nodular shadows in both lung fields. Detailed investigations resulted in
      a diagnosis of multiple lung metastasis of anaplastic thyroid carcinoma
      transformed from papillary adenocarcinoma. Both serum CA 19-9 and GM-CSF levels
      were elevated, to 70.5 U/ml (normal range: 0-37 U/ml) and 343.4 pg/ml (normal
      range: 0-8 pg/ml), respectively. Immunostaining disclosed that the primary and
      metastatic tumors were positive for CA 19-9, but not for GM-CSF antigens. Serum
      levels of these two parameters slowly decreased after chemo-radiotherapy,
      suggesting that the tumor may have produced GM-CSF as well as CA 19-9. Recent
      studies have indicated that the prognosis is poor for non-small cell lung cancers
      that produce G-CSF or CA 19-9. To our knowledge, this is the first case report of
      anaplastic thyroid carcinoma characterized by high serum levels of both CA 19-9
      and GM-CSF, with metastasis to the lung and other organs.

PMID- 10921288
TI  - [Squamous cell type lung cancer that produced granulocyte colony-stimulating
      factor].
AB  - A 73-year-old man was hospitalized because of weight loss and fever. Laboratory
      data showed marked leukocytosis (21,200/mm3), granulocytosis (89.7%),
      thrombocytosis (47.8 x 10(4)/mm3), increased CRP (15.8 mg/dl), and increased SCC
      (5.0 ng/ml). Chest X-ray films demonstrated a mass shadow in the right upper lung
      field. Chest computed tomographic scans revealed a mass shadow 58 mm in diameter
      with mediastinal pleural invasion in the right S1. Right upper lobectomy and
      dissection of regional lymph nodes was performed under a diagnosis of lung cancer
      (squamous cell carcinoma, T3 N0 M0 stage IIB) with concomitant infection. Serum G
      CSF was 234 pg/ml pre-operatively and 68.8 pg/ml postoperatively. The cytoplasm
      of tumor cells stained positively with anti-recombinant human G-CSF monoclonal
      antibody. No general bacteria or mycobacteria were detected within the specimen.
      Postoperatively, the patient's white blood cell count, platelet count, and CRP
      level soon decreased, and the fever disappeared. We diagnosed the disease as G
      CSF-producing squamous cell type lung cancer.

PMID- 10921289
TI  - [Successful thoracoscopic ligation and transection of racemose hemangioma of
      bronchial artery].
AB  - We used thoracoscopy for the successful ligation and transection of a racemose
      hemangioma of bronchial artery. The patient was a 61-year-old woman who had been
      admitted to our hospital because of hemoptysis. Bronchoscopic examination
      revealed bulging lesions covered with normal bronchial mucosa in the right B5 and
      B8, and bronchial arteriography revealed a shunt between the right bronchial
      arteries and pulmonary arteries and veins. Ligation and transection of the right
      bronchial artery under thoracoscopy was performed. Hemoptysis has not recurred 9
      months after the operation. Thoracoscopic ligation and transection of bronchial
      artery may be an effective and less invasive procedure for the treatment of
      racemose hemangioma.

PMID- 10921290
TI  - [Microscopic polyangiitis accompanying interstitial pneumonia with aluminum
      lung].
AB  - A 67-year-old man who had worked as an aluminum grinder had been given a
      diagnosis of pneumoconiosis. Ten years later, he was admitted with fever, dyspnea
      on exertion, and numbness. Chest roentgenograms showed linear-reticular shadows
      in both lower lung fields. ELISA-based tests were positive for perinuclear anti
      neutrophil cytoplasmic antibody (P-ANCA). Renal biopsy specimens disclosed
      crescentic glomerulonephritis and angiitis of small arteries. Our diagnosis was
      microscopic polyangiitis accompanying interstitial pneumonia with aluminum lung.
      The results of high-energy dispersion X-ray microanalysis indicated that the
      patient's lungs contained aluminum. His general condition improved with the
      administration of corticosteroid and immunosuppressive agents, and his chief
      symptoms disappeared.

PMID- 10921291
TI  - [Obstructive sleep apnea syndrome induced by ossification of the anterior
      longitudinal ligament with ankylosing spondylitis].
AB  - A 66-year-old man who had received a diagnosis of ankylosing spondylitis at the
      age of 50 was referred to our hospital for further evaluation of sleep apnea
      experienced for the last 3 years. Polysomnography yielded a diagnosis of
      obstructive sleep apnea syndrome with an apnea index of 41/hr. Computed
      tomographic scans demonstrated complete closure of the oropharynx during sleep at
      a site of marked ossification and hypertrophy of the cervical anterior
      longitudinal ligament. Nasal continuous positive airway pressure (nasal CPAP)
      with the use of chinstrap, but not nasal CPAP alone, dramatically decreased the
      patient's apnea index to 2.4/hr. We reported this case because, to the best of
      our knowledge, it is the first to demonstrate a causative association between
      ankylosing spondylitis and obstructive sleep apnea syndrome.

PMID- 10921292
TI  - [Relapse of small cell carcinoma of the lung with metastasis to iris].
AB  - We reported a case of small cell carcinoma of the lung with metastasis to the
      iris during a stage of complete remission obtained with chemotherapy and
      radiation therapy. The patient was a 55-year-old man hospitalized for hoarseness
      and abnormal chest radiographs in August 1996. Small cell carcinoma of the lung
      had been diagnosed, and the stage was limited disease. Treatment consisted of 3
      cycles of chemotherapy with cisplatin and etoposide, together with radiation
      therapy. The patient achieved complete remission and was discharged. In mid
      December, he visited an eye clinic with the complaints of blurred vision and
      congestion in the right eye. Metastatic tumor of the iris was diagnosed. At that
      time, neither local recurrence of the lung cancer nor metastasis to other organs
      were observed. The patient was treated with cisplatin and etoposide again,
      resulting in a reduction of the iris tumor's size. After chemotherapy, the right
      eye was treated with electron irradiation, and the iris tumor and other clinical
      signs almost entirely disappeared. The patient retained normal vision during the
      clinical course.

PMID- 10921293
TI  - [Measles pneumonia presenting with multiple nodular opacities on chest
      radiographs].
AB  - A 22-year-old woman presented with fever, cough, and maculopapular erythematous
      rash on hands and feet. These symptoms developed 14 days after the onset of
      natural measles in the patient's daughter. Chest radiographs obtained on the
      first examination showed multiple nodular opacities and infiltrates in the left
      and right lung fields. Serological examinations disclosed elevated levels of the
      specific IgM antibody and a remarkably elevated hemagglutination inhibition (HI)
      titer, indicating a recent measles infection. The patient's symptoms, skin
      eruptions, and abnormal chest radiograph findings disappeared after several days.
      However, chest computed tomographic scans taken 8 months after the initial
      examination revealed small, residual nodular opacities. Other than the fact that
      the patient had received attenuated measles virus vaccine, these findings were
      typical of the clinical course for atypical pneumonia. We concluded that in the
      differential diagnosis of multiple nodular opacities on chest radiographs,
      adequate attention should be given to pulmonary involvement of measles infection.

PMID- 10921294
TI  - [Balloon-occluded retrograde transvenous obliteration (B-RTO) for portal
      hypertension].
AB  - We reviewed the current techniques and published results of balloon-occluded
      retrograde transvenous obliteration (B-RTO) for gastric varices (GV) and hepatic
      encephalopathy. The portal hemodynamics of gastric varices were classified into
      three types according to their feeding vessels, and the development of collateral
      veins under balloon occlusion of gastro-renal shunt was classified into five
      grades. The main draining veins of gastric varices were gastro-renal and gastro
      inferior phrenic shunts. Preprocedural diagnosis of portal hemodynamics is
      important in selecting the technique for B-RTO. The rate of disappearance or
      marked reduction of GV was 98%, and the rate of recurrence of GV was 2%. Hepatic
      encephalopathy due to gastro-renal shunt improved markedly. In contrast,
      esophageal varices were aggravated at rates of 10% to 62.5% by the post
      procedural elevation of portal pressure. Common adverse effects were
      hemoglobinuria, abdominal pain, and low-grade fever, but ascites and pleural
      effusion were also reported. Severe complications such as cardiogenic shock,
      atrial fibrillation, and pulmonary embolism were reported. We await technical
      improvements and further indications for this procedure.

PMID- 10921295
TI  - [Clinical evaluation of the diagnosis of neuronal reversibility with acute
      cerebral infarction using ADC by diffusion weighted echo planar imaging].
AB  - The possibility of diagnosing neuronal reversibility with acute cerebral
      infarction was studied using ADC measured by diffusion weighted imaging (DWI).
      The subjects were eleven patients who underwent DWI within 24 hours of onset. The
      area of abnormal signal on DWI during the acute stage was visually compared with
      that on T2-WI in the subacute phase. ADC was calculated in the two different
      abnormal areas on DWI, which were differentiated by the presence or absence of
      abnormality on T2-WI in the subacute phase. The abnormal signals of three cases
      showed an obviously narrowed area on DWI in the acute phase compared with the
      abnormality on T2-WI in the sub-acute phase. ADCs of the ischemic areas in DWI
      abnormalities that showed no abnormality on subacute T2-WI were slightly higher
      than those of the infarct areas with remaining abnormal signals on T2-WI.
      However, no statistically significant difference was found between these two
      regions, because there were large variations within each pixel. We considered
      that the diagnosis of neuronal reversibility in acute cerebral infarction was
      difficult using ADC values only and that other parameters such as perfusion or
      blood volume will be necessary to improve diagnostic quality prior to determining
      therapy.

PMID- 10921296
TI  - [Metallic stent placement for iliac artery occlusive disease].
AB  - Since 1991, we have performed stent placement for 35 iliac artery lesions in 31
      patients. The etiologic diseases were atherosclerotic in 34 patients and
      traumatic dissection in one. The indications of placement were total occlusion in
      3, late restenosis after angioplasty in 5, dissection in 5, and residual stenosis
      due to inadequate angioplasty in 21. We also performed direct stent placement for
      one traumatic dissection. The stents used were Wallstents in 10, Palmaz stents in
      14, Strecker stents in 9, and Memotherm stents in 2 lesions. Follow-up was
      performed clinically or angiographically with measurement of the ankle/arm
      pressure index. Stent placement was successful in all cases, and relief or
      improvement of symptoms was achieved. The follow-up period ranged from 6-85
      months (mean, 37.3 months). Late stent stenosis or occlusion occurred in 6 cases,
      among which 4 occluded lesions were successfully recanalized by thrombolytic
      therapy with angioplasty or second stent placement. In total, the primary patency
      rates were 88% and 77% at two and four years, respectively, while the secondary
      patency rates were 94% and 94%. In conclusion, metallic stent placement may offer
      extended application of intravascular treatment for iliac artery occlusive
      disease, and good long-term patency rates can be expected.

PMID- 10921298
TI  - [Medical exposures based on the survey of the X-ray technical conditions and the
      proposal of guidance level].
AB  - The purpose of this work was to propose guidance levels of entrance surface doses
      for radiographic examinations of Japanese patients based on a nationwide survey.
      Questionnaires asking about the technical conditions of radiography were sent to
      2,000 hospitals in Japan. The entrance doses (1st quartile, median, 3rd quartile,
      and mean) were calculated by the Numerical Dose Determination (NDD) method
      described in this paper and by using the conditions reported in the
      questionnaires. Our results for all types of examinations showed that the median
      was lower than the mean, whereas the median was higher than the mean in the
      results reported in the British NRPB 21. The median of our results was lower than
      that in the NRPB in England (Present work/NRPB in England = 0.27-0.74). We
      propose guidance levels of entrance surface doses for examinations carried out in
      Japanese institutions as the 3rd quartile of the dose distributions. The present
      proposed levels are lower than those described by IAEA. The calculated entrance
      surface doses exceeded the guidance levels set by IAEA in less than 10% of the
      institutions surveyed.

PMID- 10921297
TI  - [Dynamic MRI and tumor angiogenesis of breast cancer].
AB  - The purpose of this study was to clarify the mechanism underlying early enhanced
      MR images of breast cancer by dynamic MR imaging from the aspect of tumor
      angiogenesis. The images depicted by dynamic MR imaging of breast cancer were
      divided into the following two groups: a marginal strong enhancement (MSE)
      pattern and a variable pattern without marginal strong enhancement (non-MSE).
      Twenty patients with invasive ductal carcinoma (maximum diameter < 2 cm) were
      examined by dynamic MR imaging, and the histological materials were submitted to
      two-dimensional computer image analysis with immunohistochemistry and
      histochemistry; morphological microvessel characteristics and microvessel density
      were examined; and the expression of vascular endothelial growth factor (VEGF)
      was investigated. In the MSE cases, vessel wall irregularity of capillaries and
      venules in the peripheral area adjacent to the tumor correlated (p < 0.001) with
      the enhancement pattern, and the total microvessel density (especially of
      arterioles with a maximum diameter less than 50 microns) of the peripheral area
      adjacent to the tumor was significantly higher than that of the tumor area.
      However, in the non-MSE cases, total microvessel density showed no significant
      difference between the peripheral area adjacent to the tumor and the tumor area,
      whereas the capillary density of the tumor area was four times greater than that
      of the peripheral area adjacent to the tumor. The expression of VEGF was strongly
      positive for the tumor nest adjacent to the capillaries. These results suggest
      that the enhanced images of the MSE pattern depend on abundant blood supply from
      arterioles and that the images of the non-MSE pattern might be reflective of
      angiogenic activity including variable VEGF expression of tumor cells. Thus the
      mechanism underlying early dynamic MR images of breast cancer was a complex
      result of tumor angiogenesis and the microcirculatory environment.

PMID- 10921299
TI  - [Study on evaluation method of patient dose in diagnostic radiology required for
      introducing the guidance level: investigation of entrance surface dose of patient
      using direct measurement by TLD].
AB  - Using direct measurement, we investigated entrance surface doses of patients for
      routine radiographs in attempt to develop evaluation methods of patient dose in
      order to establish the guidance level in Japan. To date, patient doses have been
      evaluated by calculations based on radiographic conditions, or model experiments
      using phantoms. Their patient doses are then evaluated based on several
      assumptions. Direct measurement of patient dose is difficult to perform in many
      patients due to its time requirement, level of expertise required and difficulty
      in providing an explanation of the procedure to the patient. However, such direct
      measurement is essential since it incorporates all aspects of radiography from
      the radiographic equipment used, to the actual conditions of each patient without
      assumption. In this study, we examined the (1) need for introducing the guidance
      level, (2) controversial points in the calculation method for patient dose
      evaluation, (3) evaluation accuracy required for introducing the guidance level,
      and (4) necessity for a standardized method.

PMID- 10921300
TI  - [Efficacy of stress management classes at a health center].
AB  - Although interest in mental health promotion has recently been increasing, the
      most appropriate approaches remain to be determined. Therefore we conducted
      Stress Management Classes (SMCs) at Higashi Osaka City Naka Health Center in an
      attempt to help residents to improve their mental health. The purpose of this
      study was to evaluate the efficacy of SMCs, held four times over 2 months, with
      an educational program including the concept of stress and instruction in
      autogenic training as a relaxation technique. Subjects who attended a Health
      Promotion Class (HPC) at Osaka Prefectural Kaizuka Health Center were used as
      controls for the study. The aim of the HPC was to prevent chronic physical
      diseases such as hypertension, diabetes, and hyperlipidemia, with the program
      consisting mainly of exercise once a week for 3 months. The results were as
      follows: 1) People who attended SMCs were more likely to have mental health
      problems than those who attended the HPC. As a result, mentally ill patients
      could be diagnosed and receive psychiatric treatment at an early stage in the SMC
      group. 2) Both SMC and HPC attenders reported improvement of their mental health
      status with the use of POMS (Profile of Mood States). 3) Both SMC and HPC
      attenders exhibited significant decrease of blood pressure. Although attenders of
      both classes improved their mental health status, it is important to be able to
      attract individuals who are in a poor mental condition in case of mental health
      promotion. In this trial, we found that the term "stress management" was very
      useful because people who suffered stress were likely to be interested in it.
      After the Community Health Law was established in 1994, the flow of community
      health activities has been shifting from the prefectural government to the
      municipality. However, promoting mental health and welfare is still mainly the
      role of the prefectural government. In this sense, health centers are appropriate
      institutions to hold classes as in this trial.

PMID- 10921301
TI  - [Simple screening test for dementia in elderly persons the time and charge test].
AB  - Dementia, with its associated morbidity and mortality, has emerged as a leading
      public health problem with elderly persons and its early detection is of obrious
      importance for treatment in curable cases and referral of patients to optimal
      medical facilities with education support for family members. While the precision
      of detecting demented subjects by the existing screening methods has improved in
      recent years, they are still complex and time consuming in practice and therefore
      difficult to use. We have developed an screening method adapted for Japanese
      based on "The Time and Charge Test" of Froehlich and coworkers. The time test
      evaluates the understanding of clock hands indicating 11:10, and the charge test
      the ability selecting 100 yen from a group of coins consisting of one 50-yen
      coin, seven 10-yen coins and seven 5-yen coins. This test was conducted on 40
      persons (two out of whom dropped out) living in Roken facility (a health facility
      for the elderly) and another 40 visiting a day care center for the elderly. The
      test results were studied using Mini-Mental State Examination and Hasegawa's
      Dementia Scale-revised version. The sensitivity of our test was 49.1%, the
      specificity 95.2%, the negative predictive value 40.8%, and the positive
      predictive value 96.6%. When a time limit 5 seconds for completing the task for
      the time test and 20 seconds for the charge test, the sensitivity was 87.7%, the
      specificity 57.1% the negative predictive value 63.2%, and the positive
      predictive value 84.7%. As for reproducibility, test-retest gave a value of
      85.0%, and the inter-observer agreement was 89.5%. This simple method thus
      appears useful for screening for dementia.

PMID- 10921302
TI  - [Study of appropriate surveillance of health appraisal for communities].
AB  - A study to determine the appropriate surveillance of health appraisal for
      communities was made using individual data for deaths in 1992-1996 in Maniwa
      County (population 51,000), individual data of medical examinations from 1995 to
      1997 in Maniwa and other county (population 24,000), rate for people receiving
      medical examinations from 1983 to 1996 in Maniwa County and life table data for
      Japanese males in 1995. The results obtained were as follows: (1) The total YPLL
      (Years of Potential Life Lost) rate was reversely correlated with the proportion
      of people who had a medical examination as compared to the total population, with
      a time lag of about 6 years (P < 0.05). It can be concluded that past health
      appraisal may influence future indicators of death with a time lag of about 6
      years. (2) In the case of calculation of Years of Potential Life Lost rate (YPLL
      rate = sum of ?target age - (death age + 0.5) between n1 and n2
      ages?/population), if the target age is close to the n2, the number of deaths
      close to the n2 have a possibility of very small evaluation to influence of
      number of these near to n1. Therefore a target age must be set up some years
      above n2. (3) There is a peak point (about 90 years) among 0 and 99 years old for
      the YPLL rate in life tables for Japanese males in 1995 using the target age of
      100. On the other hand, using a target age of 120 there was a linear increasing
      from about 75 age with no peak. Then, if YPLL rate with a target age of 100 is
      used, there may be big different values among n2 before peak age and after peak
      age. (4) To perform appropriate surveillance of health appraisal for communities
      (population size: 1000-2000), two indicators must be used. One is a simple rate
      for number of death peoples of some diseases to total population or of peoples
      who have an abnormal indicator on some medical examinations to total number of
      peoples who have a medical examination, in which case that person's age is not be
      considered. The other is Age-Adjusted YPLL or YPHL (Years of Potential Health
      Lost) rate not using a data of standard population that have been showed next
      equation. A target age should be set at 120, as a maximum age of human life
      rather than 80 or 100. Age - Adjusted T(n1 - n2) YPLL rate(by Inoue) [formula:
      see text] T: A target age (value of 120 is appropriate), n1: youngest individual
      age, n2: oldest age, i; individual age between n1 and n2, pi: population (in the
      case of YPHL rate, it shows a number of peoples receiving medical examination) at
      age of i, Qi: number of death on some disease (number of peoples who have an
      abnormal indicator on some item of medical examination) at age of i.

PMID- 10921303
TI  - [Functional changes in one-year and related factors among community-dwelling
      frail elderly].
AB  - PURPOSE: The purpose of this study was to investigate physical and psychosocial
      characteristics together with life activities related to functional changes among
      frail elderly, including J-rank individuals able to walk outdoors and take a bus
      as well as people of A-rank capable of moving around inside the house but
      incapable of going outside. METHODS: The study design was of longitudinal type.
      Participants were community-dwelling frail elderly, 61 J-rank and 90 A-rank
      individuals aged over 65-years and caregivers. Nurses conducted home interviews
      as Wajima City, Ishikawa Prefecture in Japan, in 1998 at the baseline and 1999 at
      follow-up, and evaluated the degree of independence of the frail elderly. With
      the baseline survey, physical function, psychosocial characteristics, and life
      activities were assessed. RESULTS: At the follow-up survey, 3.3% people of J-rank
      elderly had died and 83.6% were at home. Among the A-rank elderly, 11.1% had died
      and 80.6% were at home. Functional change in one-year was as follows: 31.4%
      people of J-rank had declined and 68.6% remained the same. 19.4% people of A-rank
      improved, 65.3% unchanged, and 15.3% declined. Among J-rank elderly, functional
      decline was significantly related to low ADL level and less verbal contact with
      their caregivers. Life activities such as getting out to the garden or around the
      house, worshipping at a temple, doing house chores, shopping, and gardening,
      related to maintained function. Among A-rank elderly with the low ADL, function
      similarity declined. Life activities such as visiting friends, gardening, and
      performing self-care chores were significantly linked to improvement.
      CONCLUSIONS: The results suggest that the degree of independence of frail elderly
      may easily change. ADL is related to functional change among frail elderly of
      both A and J rank. It is recommended that facilitating activities like house
      chores or getting out the house for J-rank individuals and self-care for A-rank
      elderly is important to prevent functional decline. Preventive community-based
      care for frail elderly should therefore be directed of supporting their active
      life.

PMID- 10921304
TI  - [A follow-up study on continuation of daycare for the dementia elderly].

PMID- 10921305
TI  - [A study on staff of health instruction on school nurse teacher at junior high
      school].

PMID- 10921306
TI  - [Genetic epidemiology of hereditary tumor].
AB  - The last decade has seen many great successes in isolating genes involved in
      inherited disease, a process that is now scaled up by Human Genome Project. The
      identification of genes responsible for hereditary tumors has made it possible to
      do the genetic diagnosis of hereditary tumors. However, the benefits and limits
      of genetic testing for cancer susceptibility are different in each hereditary
      tumor. It is important to continue the analysis of significance(frequency and
      penetrance) of mutations of cancer predisposition genes and to make clear the
      genotype-phenotype and other correlation. Hereditary breast cancer and hereditary
      non-polyposis colorectal cancer are reviewed and the significance of genetic
      epidemiology of hereditary tumor is discussed.

PMID- 10921307
TI  - [Indications and problems of presymptomatic diagnosis and prophylactic surgery
      for hereditary cancers].

PMID- 10921308
TI  - [Nevoid basal cell carcinoma syndrome].
AB  - The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder
      characterized by multiple cutaneous basal cell carcinomas, jaw keratocysts and a
      variety of other tumours, and developmental abnormalities. Recently, this
      syndrome was shown to result from germ line mutations in human patched(PTC) gene,
      which encodes a membrane receptor and functions as an important developmental
      regulator and a tumour suppressor. Haploinsufficiency for the PTC locus is likely
      to give rise to developmental abnormalities characterized by symmetrical defects
      and malformed spine and ribs. Postnatal loss of the normal PTC allele leads to
      multiple basal cell carcinomas and other cancers. PTC mutations and loss of the
      remaining wild-type allele have also been identified in sporadic basal cell
      carcinomas and meduloblastomas.

PMID- 10921309
TI  - [Familial malignant melanoma].
AB  - Patients with familial malignant melanoma(FMM) are susceptible for melanoma and
      multiple dysplastic nevi(atypical mole). FMM is also called as dysplastic nevus
      syndrome or familial atypical mole and melanoma syndrome. The number of Japanese
      patients with FMM is very low. In 1994, p16(MTS1, INK4A, CDK4I, CDKN2) gene was
      cloned as the gene for FMM. p16 gene locus also codes for p14ARF and acts as
      tumor suppressor through activation of Rb by p16 and p53 by p14ARF. Approximately
      20% of FMM patients were shown to carry the germline mutations of p16, indicating
      the presence of another gene or other genes for FMM, which also may be involved
      in the development of sporadic malignant melanoma.

PMID- 10921310
TI  - [Clinical features and current progress of familial adenomatous polyposis].
AB  - Familial adenomatous polyposis(FAP) is inherited disease as an autosomal dominant
      trait in which the large intestine is diffusely carpeted by numerous adenomas
      with a high incidence of colorectal cancer. Current clinical aspects and
      biological progress were discussed with emphasis on diagnostic imaging, natural
      histories of gastrointestinal polyps and intra-mandibular osteomas. Genotype
      phenotype correlation including attenuated type and function of APC gene,
      identified in 1991 as a responsible tumour suppressor one for FAP and Gardner
      syndrome, were also reviewed.

PMID- 10921311
TI  - [Hereditary nonpolyposis colorectal cancer].
AB  - Hereditary nonpolyposis colorectal cancer(HNPCC) is one of the most common cancer
      predisposition syndromes. Mismatch repair genes, such as hMSH2 and hMLH1, have
      been identified as causative genes for most HNPCC cases. When we examined the
      hMLH1 and hMSH2 genes on PCR-SSCP, 9 of the 15(60%) cases satisfying the
      Amsterdam criteria and 3 of the 22(13.6%) cases with the Japanese clinical
      criteria showed germline mutations, indicating a significant difference of the
      detection rate. Interestingly, the mutation frequency of hMSH2(11/12) is much
      higher than that of hMLH1(1/12). Alterations of TGF-beta RII(A)10 were found in
      8(57%) adenomas and 11(85%) cancers, and they were seen at an earlier stage of
      adenomas, suggesting a strong association of TGF-beta RII alterations with
      adenoma formation in HNPCC.

PMID- 10921313
TI  - [Characteristics of familial breast cancer].
AB  - We report the clinical characteristics of familial breast cancer families at our
      hospital in which the number of second-degree of breast cancer probands was more
      than 2. In our hospital, the incidence of onset at a young age was 21.9%, and
      bilateral breast cancer was 10.5%. These incident rates were significantly higher
      than sporadic breast cancer. The frequency of familial breast cancer in most
      Japanese hospitals was about 1.1%, but was 2.0% in our hospital. Familial breast
      cancer is a rare breast cancer, but the risk is high in breast cancer families.
      Therefore, it is necessary to follow up not only patients but the families.

PMID- 10921312
TI  - [Peutz-Jeghers syndrome].
AB  - Peutz-Jeghers syndrome(PJS) is an autosomal dominant disease which is
      characterized by melanin spots on lips and buccal mucosa, and multiple
      gastrointestinal hamartomatous polyps. Patients are at risk of forming carcinomas
      in the gastrointestinal tract, uterus, ovary, breast and other organs. The
      LKB1(STK11) gene at chromosome 19p13.3 has been identified in 1998 as the
      causative gene for PJS, and germline mutations of this gene have been detected in
      about 50 PJS families. These mutations include nonsense mutations, frameshift
      mutations and missense mutations, all of which are assumed to inactivate the LKB1
      gene. LKB1 gene appears to be a tumor suppressor gene, and inactivation of this
      gene through germline mutation and loss of normal allele may develop
      hamartomatous polyps. However, the function of LKB1 and mechanism of carcinoma
      formation are still unclear.

PMID- 10921315
TI  - [Retinoblastoma].
AB  - Hereditary retinoblastoma is different from non-hereditary retinoblastoma in the
      following ways. It has a germinal mutation of Rb gene located in 13q14. Its
      inheritance is autosomally dominant with 80% penetrance. Retinal tumors are
      present usually multiply (average number is three) in both eyes. The patients are
      found at a younger age than those non-hereditary retinoblastoma. About 5% of them
      are accompanied by a pineal tumor or paracellular neuroectodermal tumor, in such
      cases they are called trilateral retinoblastoma. Secondary malignancies such as
      osteosarcoma and rhabdomyosarcoma are more frequent, and they are the main causes
      of death of patients with hereditary retinoblastoma. Considering these facts,
      education of patients and their family members and development of new modalities
      of treatment for preserving eyeballs without inducing secondary malignancies are
      important.

PMID- 10921314
TI  - [Familial ovarian cancer].
AB  - Ovarian cancer is the most lethal disease in gynecological malignancy.
      Approximately 5-10% of cases are thought to have a hereditary basis, and family
      history is the strongest risk factor for the development of the disease. Familial
      ovarian cancer occurs as a part of three clinically distinct syndromes, site
      specific ovarian cancer families, breast ovarian cancer families, and hereditary
      nonpolyposis colorectal cancer (Lynch syndrome II) families. The breast ovarian
      cancer susceptibility genes BRCA1 and BRCA2 are reported to account for around
      50% of familial ovarian cancer families. In this paper, we describe the
      contribution of ovarian cancer susceptibility genes to familial ovarian cancer,
      and clinical features of ovarian cancer patients with germline mutations of BRCA1
      and BRCA2.

PMID- 10921316
TI  - [Wilms' tumors and malformation complexes].
AB  - Wilms' tumor is an embryonal tumor which is derived from metanephric metanephric
      blastema. The occurrence of both sporadic and hereditary forms, along with
      various congenital abnormalities of Wilms' tumor suggest that the tumors develop
      when a predisposing germ line mutation is accompanied by a second mutation. The
      existence of both gross chromosomal abnormalities has led to the genetic
      characterization of a number of loci involved in the development of Wilms' tumor.
      A tumor suppressor gene for Wilms' tumor, WT1, has been isolated from the 11p13
      region. The product of this gene is a transcription factor with four zinc
      fingers. Because of expression of WT1 is limited to the developing glomeruli of
      the kidneys and the genital ridge, it is thought to have a functional role in
      renal and gonadal organogesis. Thus dysfunction of WT1 causes loss of normal
      regulation of proliferation and leads to tumor formation and occurrence of Wilms'
      tumor anomaly complexes. The role of the imprinting genes, H19 and IGF2 in
      oncogenesis of Wilms' tumors are also discussed.

PMID- 10921317
TI  - [Characterization of the neurofibromatosis type 1 gene and neurofibromin's role
      in cells].
AB  - Neurofibromatosis type 1(NF1), a pleiotrophic autosomal dominant disorder, was
      first described in 1882 by Friedrich Daniel von Recklinghausen. The cloning of
      the NF1 gene located at 17q11.2 revealed that the gene contains 60 exons and
      spans 350 kb of genomic DNA in 1990. The gene product of NF1 is neurofibromin.
      Neurofibromin is a major negative regulator of the Ras pathway in cells, which
      transmits mitogenic signals to the nucleus through the cascade of MAP kinase.
      Loss of neurofibromin in patients with NF1 leads to accumulation of activated Ras
      (bound to GTP), and thus increases downstream mitogenic signaling. Future
      understanding the neurofibromin's role will contribute to the development of
      agents and genetic therapies which modulate Ras-mediated signaling pathways.

PMID- 10921318
TI  - [Neurofibromatosis type 2].

PMID- 10921319
TI  - [Multiple endocrine neoplasia 1 (MEN 1)].
AB  - Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant familial
      cancer syndrome characterized by tumors in parathyroids, enteropancreatic
      endocrine tissues, and anterior pituitary. In 1997, the MEN 1 gene was identified
      and cloned. It is on chromosome 11q13 and has 10 exons. It encodes a 610 amino
      acid protein called MENIN. However, many different germline mutations in MEN 1
      families have reported, there were no hotspot of mutation. The correlation
      between MEN 1 mutation and clinical datas has not been established yet. Recently,
      the possible function of MENIN protein has reported. The identification of MEN 1
      mutation by employing DNA test, will facilitate early diagnosis and treatment.

PMID- 10921320
TI  - [Multiple endocrine neoplasia type 2; MEN 2].
AB  - Multiple endocrine neoplasia type 2 (MEN 2) is an inherited disorder as an
      autosomal dominant trait, characterized by medullary thyroid carcinoma (MTC). MEN
      2 is classified with associated diseases into three subtypes: MEN 2A, MEN 2B and
      familial MTC. It has recently been shown to be associated with germline mutation
      in the RET proto-oncogene. Genetic testing allows easily for accurate diagnosis
      of presymptomatic gene carriers and surgical treatment at an early stage of the
      disease. In this review we delivered the classification, clinical feature,
      mutation in RET, mutation analysis, and management of MEN 2, and we discuss
      recent progress of research on the molecular basis and how genetic testing could
      be used for clinical management of affected patients or individuals in at-risk
      families.

PMID- 10921321
TI  - [Li-Fraumeni syndrome].
AB  - Germ-line p53 point mutations have been reported for various families with Li
      Fraumeni syndrome (LFS) characterized by a dominantly inherited increased
      susceptibility for the development of early age of onset neoplasms of diverse
      origin in multiple family members. Recently Bell et al reported that mutations in
      a known checkpoint gene called Chk2 cause some cases of LFS. This review will
      present the effective interaction of epidemiologic method and molecular genetics
      on the identification of cancer predisposition and will discuss about various
      problems of predictive testing for inherited mutations in cancer susceptibility
      genes.

PMID- 10921322
TI  - [Von Hippel-Lindau disease].
AB  - The von Hippel-Lindau (VHL) disease is a multitumor syndrome characterized by CNS
      hemangioblastoma, pheochromocytoma and renal cell carcinoma. The VHL disease gene
      is a putative tumor suppressor gene responsible for VHL disease. VHL disease
      without pheochromocytoma (pheo) and those with pheo are classified as type 1 or
      type 2, respectively. Germline missense mutations are clustered in 4 regions in
      the VHL gene. The VHL protein is now regarded as a one of the key protein for
      ubiquitination and further degradation of certain transcription factors such as
      hypoxia inducible factor (HIF). Since almost of germline mutations are
      detectable, presymptomatic diagnosis of the VHL disease with DNA analyses is
      important to improve the prognosis of VHL disease.

PMID- 10921323
TI  - [Tuberous sclerosis].
AB  - Tuberous sclerosis is an autosomal dominant disorder in which patients develop
      hamartomatous lesions in many different organs, most commonly in the brain,
      heart, kidney and skin. Two TSC-determining loci have been mapped to chromosomes
      9q34 (TSC1) and to 16p13.3 (TSC2). These genes act as tumor suppressor genes, but
      the mechanism of hamartomatous growth is not completely understood. Recently, the
      prevalence of TSC is increased by new developments such as the imaging
      techniques. However, in some cases, physicians were not able to diagnose some TSC
      individuals because they were asymptomatic or because their symptoms or signs
      were various. In this review, we present the clinical features and molecular
      analysis.

PMID- 10921324
TI  - [Bloom syndrome].
AB  - Bloom syndrome (BS) is a rare genetic disorder characterized by small body size,
      sunsensitivity, immunodeficiency and a high predisposition to various types of
      cancer. BLM was identified as the causative gene for BS, and BLM protein is
      homologous to DNA helicase. In 1995 the causative gene for BS was identified
      using somatic crossover point mapping and termed BLM. BLM is a 4437 bp cDNA that
      encodes a 1417 amino acid peptide which is homologous to ATP-dependent DNA
      helicases. DNA helicases are the enzymes which catalyze the unwinding of double
      stranded DNA to provide single- stranded templates for the processes of
      replication, repair, recombination and transcription. BLM is a member of the RecQ
      helicase family, consisting of human WRN, RECQL and yeast Sgs1. The BLM protein
      translocates into the nucleus and the distal arm of the bipartite basic residues
      in the C-terminus of the BLM protein is essential for targeting the nucleus.
      Here, we also describe relationship between the BLM gene and the cancer.

PMID- 10921325
TI  - [Fanconi anemia].
AB  - Fanconi anemia is a rare autosomal recessive disorder which is characterized with
      chromosomal fragility and hypersensitivity to DNA cross-link agents. There are
      large variability in phenotype even among patients of single family. Therefore,
      diagnosis depends solely on hypersensitivity to DNA cross-link agents. At present
      at least 8 complement groups are known and 3 genes, FANCA, FANCC and FANCG, have
      been cloned. There is controversies concerning intracellular localization and
      interaction between these genes. Although the mechanism of the final effect of
      products of these genes leading to Fanconi anemia phenotype, chromosomal
      fragility and ultimately development of cancers is not fully understand,
      increasing evidence shows that gene products seems to work to prevent oxygen
      injury by reactive oxygen species rather than repair of DNA injury.

PMID- 10921326
TI  - [Multiple exostoses].
AB  - Multiple exostoses is a hereditary disease characterized by multiple
      osteocartilagenous tumors, of which the histological structures are similar to
      those of normal epiphyses. Genetic linkage has identified three different loci
      for this disease: EXT1 on 8q, EXT2 on 11p, and EXT3 on 19p. The EXT1 and EXT2
      genes were recently isolated and mutation analyses have been performed in a
      number of patients with different ethnic backgrounds. The data indicate that
      mutations of these genes occurred in broad regions of each gene, and the loss-of
      function mutations were predominant, although there were some missense mutations
      that may create functionally defective protein. Tumor cells were shown to be
      homozygous for the mutant allele, which is consistent with the concept of these
      genes as tumor suppressor genes. Recent progress for the functional analyses has
      disclosed that these genes encode the protein with glycosyltransferase activity
      and regulate the diffusion of Hedgehog protein, which is the key molecule for the
      skeletal development. Further analyses of these genes may provide us with the
      knowledge for the development of epiphyses, and may open the new research field
      for the regeneration of epiphyses.

PMID- 10921327
TI  - [Cowden disease].
AB  - Cowden disease is an autosomal dominant disorder associated with an increased
      risk of developing benign and malignant tumors in many organ systems including
      the breast, thyroid, skin, central nervous system and gastrointestinal tract.
      Recently, germline mutations in PTEN (also known as MMAC1/TEP1) have been
      identified on chromosome 10q23 in Cowden disease patients. This gene is suggested
      to be a tumor suppressor gene, because coding-region mutations are observed in
      several tumor specimens or tumor cell lines. PTEN functions as a dual specificity
      phosphatase and lipid phosphatase. PTEN appears to negatively control the
      phosphoinositide 3-kinase signaling pathway for regulation of cell growth and
      survival. Furthermore, PTEN may also inhibit cell migration, spreading, and focal
      adhesion by interacting with the focal adhesion kinase.

PMID- 10921328
TI  - [Turcot syndrome].
AB  - Turcot syndrome is the association of colorectal polyposis with primary
      neuroepithelial tumors of the central nervous system such as glioblastoma and
      medulloblastoma. Including putative patients, more than 150 familial or sporadic
      cases of the syndrome have been reported in literature. Since early reports,
      there is considerable controversy regarding the modality of genetic transmission
      and the distinction from other syndromes like familial adenomatous
      polyposis(FAP). Recent molecular evidence suggests that Turcot syndrome could be
      divided into the following two entities based on the distinct genetic
      backgrounds. (1) True Turcot syndrome(autosomal recessive): Intestinal polyps are
      less in number(< 100), large in size and apt to transform to the malignant tumor.
      Brain tumor is mainly diagnosed as glioblastoma or astrocytoma and mismatch
      repair genes might be involved. (2) FAP-associated type(autosomal dominant):
      Predisposing to medulloblastoma.

PMID- 10921329
TI  - [Werner syndrome].
AB  - WS has been associated with an excess of cancer of unusual types, especially
      sarcomas. Thyroid carcinoma, the most frequent epithelial cancer in WS, accounted
      for 14% of neoplasia in Japanese with WS. The ratio of epithelial to non
      epithelial cancer was 1:1, as compared with 10:1 in the general adult population.
      Genotype/phenotype correlations may be due to a mutation that induces a site
      specific cancer or host-susceptibility factors, either genetic or environmental.
      Recently, we and others have identified WS gene(WRN) as chromosome 8p12-located
      RecQ type DNA/RNA helicase. The wild type WRN protein has the conventional RecQ
      type DNA helicase activity to unwind DNA/RNA helix. The precise functional study
      of the helicase may help the analysis of "Why and how we age and have cancer?"
      question in the near future.

PMID- 10921330
TI  - [Xeroderma pigmentosum].
AB  - Xeroderma pigmentosum(XP) is an autosomal recessive disease that is characterized
      by hypersensitivity to sunlight with high incidence of skin cancer and that
      exhibit variable neurological abnormalities in some groups. There are eight
      different complementation groups in XP; groups A through G and a variant(XP-V).
      XP-A through XP-G have a defect in nucleotide excision repair(NER), while XP-V
      has a defect in translesion DNA synthesis. Almost all of genes for XP have been
      cloned and their functions in the NER mechanism have been progressively unveiled.
      In this review, the present knowledge of the pathological features and genetic
      defects in XP has been discussed.

PMID- 10921331
TI  - [Palmoplantar keratosis].
AB  - Palmoplantar keratosis is a frequent hereditary disorder of keratinization in
      humans that have been classified into diffuse, punctate and focal forms according
      to the pattern of hyperkeratosis on the pal and soles. Various clinically,
      histopathologically and genetically distinct phenotypes can be diagnosed. Diffuse
      palmoplantar keratodermas can be further subdivided by the presence of
      epidemlysis on histopathology into epidermolytic form and non-epidermolytic form.
      The late onset non-epidermolytic palmoplantar keratoderma was found associated
      with oesophageal cancer. The causative locus designated as TOC(Tylosis with
      oesophageal cancer) mapped to a small region on chromosome 17q25. Frequent
      allelic loss was found overlapping the region in sporadic oesophageal, ovarian
      and breast cancers. Positional cloning and candidate gene analysis will allow
      identification and characterization of the TOC gene which may also be implicated
      in cancer development.

PMID- 10921333
TI  - [Beckwith-Wiedemann syndrome].
AB  - Beckwith-Wiedemann syndrome(BWS) is one of the most common overgrowth syndrome
      and is believed that imprinted genes contribute to the phenotypes of syndrome.
      Embryonic tumors are observed in 7.5%-10.0% of BWS, so BWS could be classified in
      one of the familial cancer syndrome. We describe here the causative mechanisms of
      BWS, mechanisms of tumorigenesis related to the BWS, and what to be uncovered in
      the next step.

PMID- 10921332
TI  - [Ataxia telangiectasia].
AB  - Ataxia-telangiectasia(AT), an autosomal recessive disorder characterized by
      cerebellar degeneration, immunodeficiency, cancer predisposition and radiation
      sensitivity, is caused by mutations in a gene named ATM(AT, mutated), which
      encodes a 370 kDa serine-threonine kinase, whose catalytic domain is structurally
      related to the catalytic subunit of phosphatidylinositol 3-kinase(PI3K). ATM has
      been recently revealed to be involved in DNA damage recognition and cell cycle
      control in response to ionizing radiation damage. Further investigations of the
      multiple roles of ATM will explain other disease features, such as cerebellar
      degeneration in ATM in the near future. This review summarizes some of the recent
      research developments in ATM functions and their relationship to the clinical
      phenotypes of AT.

PMID- 10921334
TI  - [Hereditary prostate cancer].
AB  - Familial prostate cancer patients are sometimes encountered. Hereditary prostate
      cancer is a more specific form of familial prostate cancer that is inherited by a
      susceptibility gene consistent with Mendelian inheritance. Early age at onset is
      the most important characteristic. No clear differences in either stage, grade or
      prognosis have been found between hereditary and sporadic prostate cancer. No
      susceptibility genes have been isolated yet, but several genes may exist. In
      Japan, doctors are not generally aware of hereditary and familial prostate
      cancer. Family history is one of the most important risk factors of prostate
      cancer. We should make an effort to find prostate cancer patients at an early
      stage in the high risk families.

PMID- 10921335
TI  - [Familial nonmedullary thyroid cancer].
AB  - Familial occurrence of nonmedullary thyroid carcinoma is rare but this has been
      increasingly recognized over the recent years. Epidemiological studies showed
      that relatives of thyroid cancer cases were at increased risk of the same site.
      Surveying published familial cases, there were two groups of familial thyroid
      carcinoma; groups related to other familial diseases(familial adenomatous
      polyposis FAP, Gardner's syndrome, Cowden's disease) and another independent of
      accompanying disease. Familial thyroid carcinomas independent of accompanying
      disease were reported aggressive features and several authors recommended
      aggressive treatments. Genetic bases has not been clearly elucidated
      identification of genetic defects should undoubtedly aid an understanding of
      pathogenesis of sporadic cases.

PMID- 10921336
TI  - [Familial gastric cancer].
AB  - Literature on familial gastric cancer was reviewed from the stand point of
      genetic and clinico-pathological aspects. Germline mutations of the E-cadherin
      gene were found in about one quarter of diffuse type cases of familial gastric
      cancer in kindreds of New Zealand and Europe, while the E-cadherin gene may not
      be responsible for most Japanese familial gastric cancer cases. It is likely that
      mismatch repair genes are not major causative genes for familial gastric cancer.
      Additional studies are necessary to elucidate the nature of familial gastric
      cancer including that of intestinal type. Prophylactic gastrectomy is effective
      in preventing gastric carcinoma, but it is not generally recommended at present
      for all E-cadherin mutation carriers in Japan.

PMID- 10921337
TI  - [Nuclear steroid hormone receptors as possible target molecule for endocrine
      disruptant].
AB  - Endocrine disruptant is supposed to act as a ligand to modulate a certain set of
      receptors. One class of the candidate receptors is the nuclear receptor
      superfamily. This family compromises nearly hundred members in human including
      steroid/thyroid hormones, vitamin A and D, other fat-soluble compounds nuclear
      receptors, and a subfamily of orphan receptors, whose ligands have not yet been
      identified. The nuclear receptors regulate transcription of target genes as
      ligand-inducible transcription factors. In this review, the functions of nuclear
      receptors are described in terms of transcriptional controls, and a possible
      target molecule for endocrine disruptants is discussed.

PMID- 10921338
TI  - [Technique for constructing recombinant adenovirus vectors and application for
      next generation vectors].
AB  - Recombinant adenovirus vectors have been used extensively to deliver foreign
      genes to a variety of cell types in vitro and in vivo. One problem with the use
      of adenovirus vectors has been the difficulty of constructing new vectors. In
      this review, we introduce not only a simple in vitro ligation method that is
      quick and efficient for generating new vectors, but also a method by which to
      construct vectors containing genetically modified fiber proteins for achieving
      targeted gene transfer and expression. The system described here should offer a
      powerful tool for the construction of recombinant adenovirus vectors for human
      gene therapy.

PMID- 10921340
TI  - [Autoreactive T cells involved in pathogenesis of ITP as a target for immune
      therapy].

PMID- 10921339
TI  - [The factor to take a part of platelet production step: distinction from
      thrombopoietin].

PMID- 10921341
TI  - [New strategy for diagnosis and therapy of ITP].

PMID- 10921342
TI  - [Thrombotic thrombocytopenic purpura: pathophysiology and treatment].

PMID- 10921343
TI  - [Adverse effects and infections caused by platelet concentrate].

PMID- 10921344
TI  - [Immune reconstitution and immunodeficiency after allogeneic hematopoietic stem
      cell transplantation].

PMID- 10921345
TI  - [Immunodeficiency and its complications of bone marrow transplantation from
      unrelated donors].

PMID- 10921346
TI  - [Complications of cord blood transplantation: graft failure and infectious
      disease].

PMID- 10921347
TI  - [Quantitative analysis of Epstein-Barr virus (EBV)-specific CD8+ T lymphocytes in
      EBV-related diseases].

PMID- 10921348
TI  - [Thrombotic microangiopathy (TMA) (1). TMA in the target organs of graft-versus
      host disease].

PMID- 10921349
TI  - [Thrombotic microangiopathy TMA (2). Clinical manifestations focusing on
      hemostatic parameters].

PMID- 10921350
TI  - [CD34+ cell dose and hematologic recovery in allogeneic peripheral blood stem
      cell transplantation].
AB  - Allogeneic peripheral blood stem cell transplantation (Allo-PBSCT) has been
      performed as an alternative to bone marrow transplantation (BMT). Here we report
      poor mobilization with granulocyte-colony stimulating factor (G-CSF) and
      engraftment kinetics in Allo-PBSCT. Sixteen patients (aged 6-61 yr, median 34 yr)
      received allogeneic peripheral blood stem cells from related donors (aged 15-68
      yr, median 37 yr) after myeloablative therapy. Nine of the patients had standard
      risk disease and 7 had high-risk disease. The donors received G-CSF at a dose of
      10 micrograms/kg/day by subcutaneous injection for 4 to 6 days. Peripheral blood
      stem cells were subsequently collected in 1 to 3 aphereses and infused
      immediately. All patients received G-CSF after transplantation. Fifteen patients
      underwent Allo-PBSCT and one underwent Allo-PBSCT plus BMT. The mean number of
      CD34+ cells infused in the 15 Allo-PBSCT patients was 6.32 x 10(6)/kg (range 1.28
      14.20). The outcomes were compared with 9 identically treated patients who
      underwent Allo-BMT. The median times until engraftment for neutrophils >
      500/microliter and platelets > 20,000/microliter were 14 (range 10-17) and 15
      (range 11-50) days in the Allo-PBSCT group and 17 (range 13-29) and 20 (range 16
      160) days in the Allo-BMT group, respectively (p = 0.0177 and p = 0.003). Three
      donors were considered to have poor mobilization (< 2 x 10(6) CD34+ cells/kg of
      the recipient); two of them yielded 1.28 and 1.78 x 10(6) CD34+ cells/kg in 3
      apheresis procedures. The patients who received cells from these donors showed
      prompt neutrophil engraftment, but one showed delayed platelet engraftment and
      another died of grade IV acute GVHD before reaching 20,000 platelets/microliter.
      An additional bone marrow harvest was necessary from one donor because of poor
      mobilization(0.17 x 10(6) CD34+ cells/kg). Thus, Allo-PBSCT results in more rapid
      engraftment. It will be necessary to clarify the minimum CD34+ cell dose for
      complete engraftment in a larger series of trials.

PMID- 10921351
TI  - [Diffuse large B-cell lymphoma showing CNS invasion by CD30-positive multinuclear
      giant cells mimicking the clinical features of progressive multifocal
      leukoencephalopathy].
AB  - We report a 55-year-old woman with diffuse large B-cell lymphoma showing central
      nervous system (CNS) infiltration by CD30-positive lymphoma cells. The patient
      was admitted with pleural effusion, ascites and a large mass in the abdominal
      cavity. Southern blot analysis of DNA extracted from the ascites revealed IgJH
      rearrangement, and therefore she was initially diagnosed as B-cell neoplasia. She
      received combined chemotherapy (DICE and CHOP regimens), and achieved a transient
      clinical response. Three months later, she developed various neurological
      abnormalities, and brain magnetic resonance imaging revealed diffuse infiltration
      of the cerebral white matter. We considered the possibility of CNS involvement by
      the lymphoma or progressive multifocal leukoencephalopathy (PML), and began a
      course of anti-virus therapy and radiation therapy. Because multiple lumbar
      punctures demonstrated large multinuclear lymphoma cells in the cerebrospinal
      fluid, a diagnosis of metastatic CNS lymphoma was made. Immunohistochemistry
      revealed that these lymphoma cells were reactive with anti-CD30 antibody.
      Although the radiation therapy was temporarily effective against the CNS
      involvement, the patient died of systemic invasion of the lymphoma cells. The
      final diagnosis was diffuse large B-cell lymphoma on the basis of pathologic
      findings, immunohistochemistry, and Southern blot analysis using a mesenteric
      lymph node obtained at autopsy. Cytospin preparations and immunohistochemistry of
      specimens obtained from frequent lumbar punctures were useful for differentiating
      CNS lymphoma from PML.

PMID- 10921352
TI  - [Complete remission of plasmablastic IgD lambda multiple myeloma induced by
      continuous infusion of low-dose cytarabine and etoposide].
AB  - A 67-year-old man was admitted because of thrombocytopenia in May 1998. His white
      blood cell count was 4,900/microliter with 3.5% blasts. Laboratory findings were
      as follows: hemoglobin level, 10.1 g/dl; platelet count, 1.8 x 10(4)/microliter;
      ALT, 56 IU/l; LDH, 3,570 IU/l; IgG, 653 mg/dl; IgA, 64 mg/dl; IgM, 49 mg/dl; IgD,
      674 mg/dl. Serum immunoelectrophoresis confirmed IgD lambda M-component. Bone
      marrow aspiration showed 79.2% myeloma cells expressing a mostly plasmablastic
      morphology. No mature plasma cells were found in the bone marrow. The patient
      received a continuous drip infusion of 20 mg/body cytarabine (Ara-C) and 50
      mg/body etoposide (VP-16) for 7 days. No plasmablastic myeloma cells were
      detected, but 2.1% mature plasma cells were found in his bone marrow on day 20.
      On day 18 his platelet count exceeded 10.8 x 10(4)/microliter, and the serum IgD
      level fell to 210 mg/dl. Therapy consisting of melphalan, methylprednisolone and
      vincristine was started from day 23. No IgD lambda M-component was detectable by
      serum immunoelectrophoresis seven months after the diagnosis of multiple myeloma.
      The patient has been in complete remission as of April 2000.

PMID- 10921353
TI  - [Subcutaneous panniculitic T-cell lymphoma with chromosomal abnormalities and
      large granular lymphocytes morphology].
AB  - A 72-year-old woman was admitted because of a subcutaneous hip tumor. A biopsy
      specimen of the tumor showed a mixture of medium-sized and large lymphocytes
      infiltrating the subcutaneous fat tissue with a lobular panniculitis-like pattern
      -a histologic feature of subcutaneous panniculitic T-cell lymphoma (SPTCL). May
      Grunwald-Giemsa-stained cytospin slides of freshly isolated neoplastic cell
      explants showed that the cells had the characteristics of large granular
      lymphocytes. Immunophenotypic analysis showed that the cells expressed CD56--a
      natural killer-associated antigen--as well as the cytotoxic T-cell phenotype CD3+
      CD4- CD8+. Southern blot analysis revealed rearrangement bands of the TCR-beta
      chain gene. Chromosome analysis showed complex abnormalities including t(1;6)
      (q11; p21). The present case may shed some light on the origin and pathogenesis
      of SPTCL.

PMID- 10921354
TI  - [Genetic analysis of a patient with dyskeratosis congenita].
AB  - Dyskeratosis congenita (DKC) is a rare inherited disease characterized by
      reticulated pigmentation of the skin, nail dystrophy and oral leukoplakia. More
      than 90% of DKC cases are inherited as an X-linked recessive trait. Half the
      patients develop progressive pancytopenia by the age of 11 yr, and this is the
      leading cause of death. We experienced a 11-year-old boy with the above
      symptomatic triad of DKC, complicated by progressive pancytopenia as well as
      cerebellar ataxia. Genetic analysis of mRNA from his cultured peripheral
      lymphocytes revealed a missense mutation resulting in substitution of 1,150 C
      with T in the DKC1 gene. This is identical to the mutation reported by Knight et
      al. to be prevalent in X-linked cases of DKC (11 out of 21 patients). Existence
      of the identical mutation in Japan suggests that this mutation has been selected
      on the basis of not only the DNA structural sequence of dyskerin, but also its
      biological function. We report the detailed clinical course of this Japanese DKC
      patient with a mutation in the DKC1 gene, and describe the results of genetic
      analysis.

PMID- 10921355
TI  - Medical tourism as medical harm to the Third World: Why? For whom?

PMID- 10921356
TI  - Larval habitat characterization for Aedes triseriatus (Say), the mosquito vector
      of LaCrosse encephalitis in West Virginia.
AB  - OBJECTIVE: The principal aim of this investigation was to provide quantitative
      information on the frequency of occurrence for Aedes triseriatus (Say) larvae in
      West Virginia at 3 broad elevation categories, in different months of the year,
      and in specific types of larval habitats. METHODS: Larvae were collected in 54
      West Virginia counties over a 6-year period, and their occurrence was recorded
      for defined habitat categories. RESULTS: Aedes triseriatus larvae were collected
      at 206 of the 587 sites examined and in 48 of the 54 West Virginia counties
      sampled. CONCLUSION: Aedes triseriatus larvae are distributed equally across all
      elevation categories from March through October and are predisposed to shaded
      habitats.

PMID- 10921357
TI  - Acclimatization near home? Early respiratory changes after short-term
      intermittent exposure to simulated altitude.
AB  - OBJECTIVE: With the ultimate goal of finding a straightforward protocol for
      acclimatization at simulated altitude, we evaluated the early effects of repeated
      short-term exposure to hypobaric hypoxia on the respiratory response to exercise
      in hypoxia. METHODS: Nine subjects were exposed to a simulated altitude of 5000 m
      for 2 hours a day for 14 days. Arterial oxygen saturation (SaO2), expired volume
      per minute (VE), respiratory rate, tidal volume (VT), and heart rate were
      measured during rest and during exercise (cycloergometer, at 30% of maximum
      oxygen consumption at sea level), both in normoxia and at 5000 m of simulated
      altitude on the first and 15th days. On the same days, blood samples were
      obtained for hematological tests. RESULTS: During exercise in hypoxia, SaO2 rose
      from 65 to 71% (P = .02), and VE rose from 55.5 to 67.6 L.min-1 (P = .02) due to
      an increase in VT from 2 to 2.6 L (P = .003). No significant differences were
      found in any of the variables studied at rest either in normoxia or in hypoxia or
      in exercise in normoxia after the exposure program. In the second week, changes
      in packed cell volume and blood hemoglobin concentration were nonsignificant.
      CONCLUSIONS: After short-term intermittent exposure to hypobaric hypoxia,
      subjects increased their ventilatory response and SaO2 during exercise at
      simulated altitude. These changes may be interpreted as acclimatization to
      altitude. The monitoring of ventilatory response and SaO2 during moderate
      exercise in hypobaric hypoxia may be used to detect the first stages of
      acclimatization to altitude.

PMID- 10921358
TI  - Disoriented and ataxic pilgrims: an epidemiological study of acute mountain
      sickness and high-altitude cerebral edema at a sacred lake at 4300 m in the Nepal
      Himalayas.
AB  - OBJECTIVE: To determine the incidence of high-altitude cerebral edema (HACE),
      acute mountain sickness (AMS), and high-altitude pulmonary edema (HAPE) in
      pilgrims. Although it is well known that western trekkers suffer from acute
      mountain sickness (AMS) in the Himalayas, not much is documented about the
      incidence of AMS in the local population of Nepal that go to high altitude.
      METHODS: The design was a randomized study set at a sacred high-altitude lake at
      4300 m at Gosainkund in the Nepal Himalayas. There was a control study at 1300 m
      at Pashupatinath in Kathmandu, Nepal. The subjects were pilgrims of different
      ethnic Nepali backgrounds. The Lake Louise consensus for AMS, HACE, and HAPE was
      used, and oxygen saturation with a pulse oximeter was performed on HACE subjects.
      RESULTS: Out of 5000 pilgrims, 228 were randomly chosen. Sixty-eight percent had
      AMS, 31% had HACE, and 5% had HAPE. The mean oxygen saturation of HACE subjects
      at that altitude was 77%, 87% being normal for 4300 m altitude. Seventy-three
      percent of the study population were men, yet women had a significantly higher
      rate of AMS (odds ratio, 4.34; 95% confidence interval, 1.83-10.68), HACE (odds
      ratio 3.15, confidence interval 1.62-6.12), and HAPE (odds ratio, 5.2; 95%
      confidence interval, 1.24-24.73). CONCLUSIONS: Such a high incidence of HACE in
      an epidemiological study using the Lake Louise criteria has, to our knowledge,
      not been reported before. High-altitude pilgrims, especially women pilgrims in
      this study, seem to be a very susceptible group. Preventive measures in these
      pilgrims need to be adopted to avoid AMS, specifically life-threatening HACE and
      HAPE.

PMID- 10921359
TI  - Injuries to avian researchers at Palmer Station, Antarctica from penguins, giant
      petrels, and skuas.
AB  - This paper describes 5 cases of injury to seabird researchers between 1996 and
      1999 at Palmer Station, Antarctica. The injuries were inflicted by 3 seabird
      species: the Adelie penguin (Pygoscelis adeliae); the southern giant petrel
      (Macronectes giganteus); and the brown skua (Catharacta lonnbergi). All injured
      parties were biologic researchers with previous field experience working under
      National Science Foundation research grants; all sought medical evaluation and
      treatment voluntarily. The nature and frequency of such injuries seems not to
      have been greatly reported in the medical literature. Although these cases were
      largely soft tissue injuries that healed without serious complications, the
      possibility of exotic infections is considered. We have dubbed this constellation
      of injuries AVES (Antarctic Vogel [German for bird] Encounter Syndrome).

PMID- 10921360
TI  - A tragic report of probable high-altitude pulmonary edema in the Himalayas:
      preventive implications.
AB  - High-altitude pulmonary edema (HAPE) is a well-recognized disease entity in
      trekkers to the Nepal Himalayas. We present the case of a patient who had
      clinical features consistent with HAPE but did not descend the mountain on time,
      which contributed to his death. The important factors of the diagnosis, the
      descent, and the follow-up in Kathmandu are examined.

PMID- 10921362
TI  - Clinical images. Short-haul release assembly--"3-ring circus".

PMID- 10921361
TI  - In-area and backcountry snowboarding: medical and safety aspects.
AB  - Snowboarding is now a well-established winter sport and a popular mode of
      mountaineering. In-area and backcountry snowboarding are defined, as well as a
      new term, glisse, that refers to all types of skis and snowboards. New
      developments in equipment focus on boot and binding systems. Backcountry travel
      is highlighted, including ascent with snowshoes, skis, a splitboard, and
      crampons. Injuries are about 4-6 per 1000 snowboarding days. Upper extremity
      injuries are most often wrist sprains or fractures. Lower extremity injuries are
      primarily ankle sprains and are generally less severe than knee injuries in
      skiers. Fracture to the lateral process of the talus has been called
      snowboarder's fracture. Backcountry injuries include avalanche suffocation and
      trauma, deep snow immersion asphyxiation, hypothermia, frostbite, dehydration,
      fatigue, acute mountain sickness, and sunburn. Specific recommendations for
      prevention and safety are discussed.

PMID- 10921363
TI  - The perspicacity of Seymour Hadwen on tick paralysis--a commentary.

PMID- 10921364
TI  - Classroom and reality: lessons from real emergencies.

PMID- 10921365
TI  - A comparison of motion sickness remedies in severe sea conditions.

PMID- 10921366
TI  - Intra-aural insects, lidocaine, and vertigo.

PMID- 10921367
TI  - Tropical sprue as a cause of traveler's diarrhea.

PMID- 10921368
TI  - Case study. Early-onset periodontitis.

PMID- 10921369
TI  - Salaries keep the bills paid.

PMID- 10921370
TI  - My love affair with periodontal disease.

PMID- 10921371
TI  - Some precautions about herbs.

PMID- 10921372
TI  - Towards consensus on the control of chronic hepatitis B and hepatitis C in the
      Asia-Pacific region.

PMID- 10921373
TI  - Epidemiology of hepatitis B virus infection in the Asia-Pacific region.
AB  - There is a wide variation of hepatitis B virus (HBV) infection in the Asia
      Pacific region. The prevalence of chronic HBV infection is lowest (<1%) in North
      America, Australia and New Zealand, 2-4% in Japan, 5-18% in China and highest (15
      20%) in Taiwan as well as several other countries in South East Asia. Perinatal
      transmission is common in HBV-hyperendemic areas. Geographical clusters of
      horizontal HBV infection have been reported in both high- and low-risk countries.
      Common sources of infection, including iatrogenic and sexual transmission, have
      been implicated. Migrant studies indicate the importance of childhood
      environments in the determination of HBV infection. Rural urban and ethnic
      differences in the prevalence of HBV infection have also been reported. There has
      been a decrease in the prevalence of HBV infection after mass HBV vaccination
      programmes in some Asia-Pacific countries, which may be due to the intervention
      of possible transmission routes through the use of disposable syringes and
      needles, screening of HBV infection markers in blood banks, and prevention of
      high-risk tattooing, acupuncture, ear-piercing and sexual contact. A striking
      decrease in the incidence of HBV infection and hepatocellular carcinoma has been
      observed among children in Taiwan and other areas where mass vaccination
      programmes have been implemented.

PMID- 10921374
TI  - Public health measures to control hepatitis B virus infection in the developing
      countries of the Asia-Pacific region.
AB  - Hepatitis B virus (HBV) infection is prevalent in the Asia-Pacific region and the
      disease burden caused by chronic HBV infection has been enormous. Although
      vaccination programmes have been implemented in the past decade, and there are
      extremely successful countries in the region, many countries still cannot afford
      a control program. These countries are often populous and highly endemic for HBV
      infection. To overcome this, aid from developed countries or private foundations
      should be actively sought. In the developing countries of this region, HBV
      infection in early childhood is the main cause of chronic HBV status, and thus
      universal vaccination of all infants is the best way to control HBV infection.
      Because of the expense and extra costs of screening pregnant women, the use of
      hepatitis B immune globulin may not be essential. To achieve the goal of
      universal infant vaccination, public education should be done in parallel with
      education of health professionals and control measures. The Asia Pacific region
      has more people with chronic hepatitis B than any other part of the world, and
      control of HBV infection in this region will no doubt be the most important and
      challenging task to be taken in the beginning of the new millennium.

PMID- 10921375
TI  - Perinatal transmission of hepatitis B virus and its prevention.
AB  - In order to prevent liver cirrhosis and hepatocellular carcinoma in later life,
      it is essential to prevent HBV infection in infants. If the mother is chronically
      infected with HBV and is also positive for HBeAg, 80-90% of the newborns become
      chronically infected, whereas if the mother is positive for anti-HBe, only some
      newborns will develop acute hepatitis or fulminant hepatitis. It is necessary to
      screen pregnant women for HBsAg and prevent mother-to-infant infection of HBV,
      treating the infant with hepatitis B hyperimmune globulin at birth, followed by
      HBV vaccination. In highly endemic areas of HBV, universal HBV vaccination of all
      newborns is advisable.

PMID- 10921376
TI  - Natural history of hepatitis B virus infection in children.
AB  - Hepatitis B virus (HBV) infection during childhood can cause acute, fulminant or
      chronic hepatitis, liver cirrhosis, and liver cancer. Approximately 90% of the
      infants of hepatitis B e antigen (HBeAg) seropositive mothers become hepatitis B
      surface antigen (HBsAg) carriers. Children chronically infected are mostly
      asymptomatic. Although liver damage is usually mild during childhood, severe
      liver disease, including cirrhosis and hepatocellular carcinoma, may develop
      insidiously for 2-7 years. Spontaneous HBeAg seroconversion occurs gradually as
      the age of the child increases. Viral replication is reduced during this process,
      which is usually preceded by an elevation of aminotransferases. In a long-term
      follow-up study, the annual HBeAg seroconversion rate was 4-5% in children older
      than 3 years of age and less than 2% in children under 3 years. The annual
      seroconversion rate of HBsAg was very low (0.56%). Age at infection, maternal
      HBsAg and HBeAg status, host immune status, and possibly the HBV strain are the
      main factors determining the course of HBV infection in children.

PMID- 10921377
TI  - Natural history of chronic hepatitis B virus infection.
AB  - In chronic hepatitis B virus (HBV) infection acquired during adulthood, which is
      the type mostly seen in the Caucasian population, there is biochemical and
      histologic regression after HBeAg seroconversion, and the risk of death from
      hepatitis B-related causes is low. In chronic HBV infection acquired during birth
      or early childhood, which is the type most commonly seen in the Asian population,
      there is a prolonged phase of immunotolerance. The immune clearance phase is
      characterized by multiple acute exacerbations preceeded by elevations in serum
      HBV DNA levels, HBeAg concentration and HBeAg/anti-HBe immune complexes. Of these
      patients, 2.4% may develop hepatic decompensation during the stage of HBeAg
      seroconversion. The development of cirrhosis occurs more frequently in patients
      with episodes of decompensation and with repeated severe acute exacerbations.
      However progression to cirrhosis can be relatively silent and can occur even in
      children. After HBeAg seroconversion, precore and core promotor mutations occur
      frequently in the Asian population. However, there is little correlation between
      the occurrence of these mutations and alanine aminotransferase elevation in
      patients who are positive for anti-HBe. Although cirrhosis develops during the
      process of HBeAg seroconversion, 68% of the complications of cirrhosis and of
      hepatocellular carcinoma occur after HBeAg seroconversion. These complications
      may still occur even after HBsAg seroclearance.

PMID- 10921378
TI  - Natural history of chronic hepatitis B virus infection in adults with emphasis on
      the occurrence of cirrhosis and hepatocellular carcinoma.
AB  - The natural course of perinatally acquired hepatitis B virus (HBV) infection has
      three phases. In the first 'immune tolerance phase', patients are HBeAg positive
      and have high serum levels of HBV DNA, but have no symptoms, normal ALT levels
      and minimal histological activity. The second 'immune clearance phase' usually
      occurs between 15 and 35 years of age, during which HBV replication declines,
      accompanied by increased serum ALT levels and inflammatory activity in the liver;
      HBeAg to anti-HBe seroconversion is then observed, frequently preceded by a flare
      of the ALT level. The average rate of spontaneous HBeAg seroconversion is 10% per
      year. In the third 'low-replicative phase', serum HBsAg persists, but HBeAg is no
      longer detectable and HBV DNA can only be detected by PCR assay. During this
      phase, patients are usually asymptomatic and liver disease is inactive; some
      patients, however, may progress to cirrhosis and hepatocellular carcinoma (HCC).
      The ultimate outcome of chronic HBV infection appears to depend on the duration
      and severity of liver injury during the immune clearance phase. About 2.1% of
      patients with chronic type B hepatitis develop cirrhosis each year. Patients who
      have a severe acute exacerbation complicated by subacute hepatic failure or who
      have recurrent episodes of acute exacerbations with bridging hepatic necrosis are
      more likely to develop cirrhosis. A significant proportion of those with HBsAg
      eventually develop HCC; they have a 100-fold increased risk of HCC relative to
      those without. The development of HCC, however, is closely related to the
      severity of the underlying liver disease. The annual incidence of HCC is only
      0.1% in asymptomatic HBsAg individual, 1% in patients with chronic hepatitis B,
      but increases to 3-10% in patients with cirrhosis. Some anti-HBe-positive
      patients continue to have active liver disease and they should be tested for HBV
      DNA by hybridization assay to determine whether the disease results from
      replicative precore mutant HBV infection or other causes of liver disease, such
      as superinfection with HCV and HDV. A substantial number of apparently healthy
      HBV-infected individuals are first recognized when they present with episodes of
      acute hepatitis. About 30% of these cases could be attributed to other
      hepatotropic virus superinfection. Acute viral hepatitis in patients with
      concurrent HBV infection is associated with an increased risk of fulminant
      hepatic failure. Finally, HBsAg disappears from serum in about 1% of patients
      each year. HCV superinfection can enhance the termination of HBsAg positivity.
      HCV, however, replaces HBV as the dominant cause of chronic viral hepatitis. The
      outcome of HBV-infected persons with 'spontaneous' seroclearance of HBsAg is
      usually favourable, though progress to cirrhosis and HCC is still possible.

PMID- 10921379
TI  - Treatment of chronic hepatitis B virus infection: who, when, what for and how.
AB  - Chronic hepatitis B virus (HBV) infection is a serious clinical problem because
      of its worldwide distribution and possible adverse sequelae. It is particularly
      important in the Asia-Pacific region where HBV infection is highly prevalent and
      usually acquired perinatally or in early childhood. It is now known that chronic
      HBV infection is a dynamic interaction between virus, hepatocyte and the host's
      immune response. The natural history of chronic HBV infection can be divided into
      three phases: high replicative or viraemic 'immune tolerance phase' followed by
      'immune clearance phase' and then the low replication 'residual phase'. The
      clinical course of chronic HBV infection is characterized by a series of
      exacerbations and remissions during the 'immune clearance phase', which may lead
      to hepatic decompensation, progression of liver disease, development of cirrhosis
      and hepatocellular carcinoma (HCC). It is of paramount importance to arrest HBV
      replication as early as possible to reduce infectivity, improve hepatic injuries,
      prevent progression to cirrhosis or HCC and thereby prolong survival. There are
      many potentially effective agents with different mechanisms of action and there
      is substantial accumulated experience with these therapies, but there is also
      still a need for practical recommendations such as: (i) who should be treated;
      (ii) when to treat such patients; (iii) which drug(s) or strategy would be most
      cost-effective for the patient under consideration; (iv) how the patient should
      be monitored; (v) what benefit the patient can expect from such treatments; (vi)
      what can be done for special groups of patients, such as decompensated cirrhosis
      immunocompromised patients or children; and (vii) what treatment of chronic HBV
      infection could be expected in the 21st century. The Asia Pacific region not only
      has the greatest number of patients with chronic HBV infection, but also has
      conducted important clinical trials. It is relevant and mandatory to coordinate
      all current knowledge to reach a consensus and to make guidelines for the
      treatment of chronic HBV infection in this region.

PMID- 10921380
TI  - Interferon monotherapy in chronic hepatitis B.
AB  - Interferon-alpha (IFN-alpha) has been the only approved agent for the treatment
      of chronic hepatitis B in most countries, but this is rapidly changing. It is
      expensive, associated with frequent and unpleasant side effects, has limited
      efficacy and is ineffective in subjects with no/mild liver necro-inflammation.
      Loss of HBsAg and viral replication markers occur 6% and 20%, more often in IFN
      treated subjects than controls. The most important factors that will predict
      favourable response to IFN-alpha therapy are elevated ALT and low serum HBV DNA
      levels. Chinese patients and children with active liver have similar response
      rates as Caucasian adults with equivalent ALT levels. Patients with HBeAg
      negative disease fare less well. Long-term follow up has shown that most IFN
      responders maintained their response although very few people have complete
      eradication of HBV.

PMID- 10921381
TI  - Role of steroid priming in the treatment of chronic hepatitis B.
AB  - Chronic hepatitis B is the result of the immunological response of the host to
      persistently replicating hepatitis B virus. Steroids can modulate this response;
      after steroid administration, viral replication increases and after drug
      withdrawal, it decreases in conjunction with a temporal increase in the
      transaminase level. Long-term decrease of the viral level is observed in some
      patients, but the beneficial effect of steroid withdrawal alone has not been
      confirmed. Interferon and other anti-viral agents can suppress virus replication,
      but the effect of these agents is still unsatisfactory. The combination of
      steroid priming and anti-viral treatment may be beneficial. Recent large-scale
      controlled trials indicate the utility of the combination therapy, but other
      randomized trials show no significant difference between therapy with or without
      steroid priming. Although steroid priming in combination with antiviral agents
      may be useful in some patients, it should be carefully performed due to the
      potential risk of liver failure.

PMID- 10921382
TI  - Use of immunomodulatory therapy (other than interferon) for the treatment of
      chronic hepatitis B virus infection.
AB  - Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In
      order to design a better therapeutic regimen, the underlying mechanism of HBV
      viral persistence must be understood. Immunological studies have found that
      impaired HBV virus-specific T cell reactivity is the major cause of chronic
      infection, whereas strong and multispecific T cell responses to HBV are
      associated with long-term control, but not elimination of the virus. Furthermore,
      in the serological clearance of hepatitis B surface antigen (HBsAg) in allogeneic
      haematopoietic cell transplantation, HBsAg seroconversion is associated with
      activation of the donor's hepatitis B core antigen-specific CD4+ T lymphocytes.
      This suggests that the donor's hepatitis B core antigen-specific CD4+ T cells
      provide 'intermolecular T cell help' for the HBsAg seroconversion. These findings
      are relevant to the future development of therapeutic vaccines or DNA vaccine as
      immunotherapy for chronic hepatitis B. Apart from interferon-alpha, thymosin
      alpha1 (Talpha1) has been investigated for treatment of chronic hepatitis B. Meta
      analysis of 4 randomized controlled studies investigating the safety and efficacy
      of Talpha1 monotherapy for the treatment of chronic hepatitis B showed that 6
      months treatment with Talpha1 (1.6 mg twice weekly) almost doubles the sustained
      response rate (36%) compared with controls (19%; P=0.04). However, more specific
      immunological approaches are being developed; notably, hepatitis B core antigen
      based therapeutic vaccine was found to induce T cell proliferative responses in
      chronically infected hepatitis B patients to the T helper epitope included in the
      construct. However, the cytokine profile observed suggested the induction of a T
      helper 0/T helper 2 CD4+ T cell response rather than T helper 1 response. Thus,
      its combination with interferon-gamma or interleukin-12, which might reverse the
      CD4+T cell response, should be considered. In the future, it is likely that
      different types of combination therapy may have to be tailor-made for chronic HBV
      infection with different virological and immunological profiles and different
      degrees of liver damage.

PMID- 10921383
TI  - Nucleoside analogues in the treatment of chronic hepatitis B.
AB  - Many nucleoside analogues have been investigated for the treatment of chronic
      hepatitis B. Some were withdrawn because of significant adverse effects and some
      are still in the early stage of clinical assessment. Lamivudine has been
      demonstrated to have consistent efficacy and safety in large-scale, phase III
      clinical trials. It has achieved a milestone in the treatment of chronic
      hepatitis B and is now commercially available in many countries. Being a potent
      inhibitor of hepatitis B viral replication, it achieved around 18% HBeAg
      seroconversion in HBeAg-positive patients after 1 year of therapy. HBeAg
      seroconversion is a good endpoint for therapy and has been shown to be 80%
      durable. The response was better among patients with raised pretreatment alanine
      aminotransferase levels. Liver necro-inflammation and fibrosis improved
      significantly after 1 year. Further improvement on extended therapy was observed
      together with an incremental increase in HBeAg seroconversion. Similar efficacy
      was demonstrated in HBeAg-negative viraemic patients. The main drawback is the
      emergence of drug-resistant variants starting from the sixth to ninth month of
      treatment. This can be associated with varying degrees of relapse of disease
      activity and may offset the benefit of therapy. With extended therapy, drug
      resistant variants continue to emergence at a rate of around 20% per year.
      Adefovir dipivoxil and entacavir are nucleoside or nucleotide analogues shown to
      suppress both the wild-type and lamivudine-resistant virus. Combination of these
      nucleoside/nucleotide analogues with immune modulators may be the answer to
      eradicate the virus in short-term therapy and avoid the issue of drug resistance.

PMID- 10921384
TI  - Treatment of chronic hepatitis B in China.

PMID- 10921385
TI  - Treatment of chronic liver diseases with traditional Chinese medicine.
AB  - Traditional Chinese medicine is still being extensively used for treatment of
      liver disease in China. The anti-viral herbs, Phyllanthus amarus, P. niruri and P
      urninaria, and Oxymatrine extracted from Sophora flavecientis and S.
      subprostratae, have been shown to have a remarkable HBV suppressing effect with a
      serum conversion rate for HBeAg and HBV DNA around 45%, similar to that of IFN
      alpha. The anti-inflammatory compound, Stronger NeoMinophagen C (SNMC), is a
      Japanese preparation of glycerrhizin, extracted from Glyceriza glabra, which has
      shown an effective rate of ALT and AST normalization and reduction to < 60 U/L in
      65.6%, and 73.5% of patients. Compound 861, made of 10 herbs with Salvia
      miltiorrhiza as its chief component, has been shown experimentally to be
      effective in suppressing fibrogenesis, enhancing collagen degradation, and
      inhibiting TIMP expression. Clinically, an open trial of 2,000 patients showed
      improvement of symptoms in 83% and normalization of serum ALT in 82%. In a
      controlled study of 107 patients with HBV-related diseases, double liver biopsies
      showed that the fibrosis reversal rate after 6 months treatment with Cpd 861 was
      78% in S2, 82% in S3 (precirrhotic stage) and 75% in S4 (early cirrhosis), as
      assessed by Scheuer's and Chevallier's criterion. In conclusion, traditional
      Chinese medicine has great potential in the treatment of chronic hepatitis B.

PMID- 10921386
TI  - Treatment of chronic hepatitis B virus infection in special groups of patients:
      decompensated cirrhosis, immunosuppressed and paediatric patients.

PMID- 10921387
TI  - Treatment of chronic hepatitis B in australia and New Zealand.

PMID- 10921388
TI  - Public health challenges in hepatitis C virus infection.
AB  - The discovery a decade ago of the hepatitis C virus (HCV) led to control of post
      transfusion hepatitis in many countries, but raised a number of further questions
      about the transmission and epidemiological distribution of the newly discovered
      virus. In some countries, the diagnosis of HCV infection has been designated as a
      notifiable condition, with doctors (or laboratories, or both) required to send
      case reports to public health authorities. Such case reports of HCV diagnosis are
      inevitably biased towards people with symptomatic presentations or a known
      history of exposure, or those who undergo screening for other purposes, such as
      blood transfusion. Another approach has been the use of serological prevalence
      surveys either making use of blood that had been taken or tested for other
      purposes or recruiting specific population groups for the explicit purpose of
      measuring HCV prevalence. A limited number of surveys have either attempted to
      obtain true random samples of geographically defined populations, or recruited
      subjects, such as pregnant women, who may be considered to be broadly
      representative of the wider population. Injecting drug use is clearly the main
      mode of HCV transmission in countries that have established comprehensive blood
      screening, and it remains a major public health challenge. Although mother-to
      child transmission is known to occur with a frequency of about 7% there is no
      proven means of prevention and very little is known about the long-term
      consequences of maternally transmitted infection. The conclusion from a number of
      somewhat conflicting studies is probably that HCV infection should not be viewed
      as a sexually transmissible infection from the perspective of population health
      strategies. However, people with HCV infection and their sexual partners should
      minimize the extent of blood contact that may occur through sexual activity.

PMID- 10921389
TI  - Transmission of hepatitis C virus in Asia: past and present perspectives.
AB  - Hepatitis C virus (HCV) infection is a major public health problem. The
      epidemiology of HCV infection in different parts of Asia is similar, with an
      average seroprevalence of hepatitis C antibody (anti-HCV) less than 2.5% in
      healthy adults. The infection is rarely seen in children. The major routes of HCV
      transmission in Asia during the past few decades have been through administration
      of therapeutic blood products and injecting drug use, similar to the pattern
      observed in other parts of the world. However, obvious parenteral routes of
      transmission only account for 30-60% of anti-HCV-positive cases, depending on the
      geographic area. Other inapparent parenteral or per-mucosal exposures, including
      medical intervention, tattooing, acupuncture, vertical and sexual transmission,
      accidental needlestick and household contact, are also possible routes of HCV
      transmission. Although screening of blood donors for anti-HCV and improvements in
      infection control have significantly decreased the exposure to HCV, it is
      believed that HCV is still spreading in some areas of Asia because of the lack of
      routine screening of donated blood, injecting drug usage, traditional medicine
      practices or medical treatment under suboptimal hygienic conditions that involve
      blood contamination, and tattooing. Accordingly, until effective and safe
      immunoprophylaxis is available, interruption of transmission routes, such as
      implementation of blood donor screening for anti-HCV, adequate sterilization of
      surgical instruments or the use of disposable medical instruments, especially
      needles and syringes, and avoidance of sharing personal grooming aids remains the
      mainstay to prevent HCV infection in Asia today.

PMID- 10921390
TI  - Natural history of acute hepatitis C.
AB  - To study the short- and long-term outcomes of acute hepatitis C, three groups of
      patients were enrolled. Of 26 patients with acute hepatitis C, 18 (69%)
      maintained HCV viraemia and 8 had cleared virus naturally at 12 months after the
      onset. Normalization of ALT was seen in all 8 patients with acute resolving
      hepatitis, but in only 1 (5%) of the 18 patients with chronic HCV infection (P<
      0.001). Changes in liver histology were analysed in 43 patients with acute
      hepatitis C who underwent repeated liver biopsy. The mean score of the fibrotic
      stage was 0.9 within 1 year of the onset, and it increased gradually up to 3.5 at
      30 years from the onset (0.1 grade/year). The fibrotic stage increased more
      rapidly in patients aged more than 50 years. In 115 patients, the mean duration
      between blood transfusion and the diagnosis of HCC increased significantly (P<
      0.001) in accordance with increasing age at blood transfusion; 35 +/- 5.3 years
      in patients aged less than 30 years, 30 +/- 4.9 years in those aged between 30
      and 40 years, and 25 +/- 6.8 years in those aged more than 40 years. In
      conclusion, approximately 70% of patients with acute hepatitis C develop chronic
      hepatitis. Once patients develop chronic hepatitic fibrosis of the liver, it
      progresses over several decades, faster in older patients.

PMID- 10921391
TI  - Natural history of hepatitis C virus infection.
AB  - Hepatitis C is a heterogeneous disease whose natural history is controversial and
      perplexing. However, it can be a pernicious disease and is responsible for
      considerable mortality and morbidity. More than 80% individuals infected with the
      hepatitis C virus (HCV) develop chronic infection; the remaining 10-20% develop
      spontaneous clearance with natural immunity. The majority of patients who develop
      chronic HCV infection are asymptomatic; but 60-80% develop chronic hepatitis as
      indicated by elevated ALT; around 30% maintain normal ALT. One-third of
      chronically infected patients develop progressive liver injury, fibrosis and
      cirrhosis over a period of 20-30 years, and 15% develop hepatocellular carcinoma.
      Acquiring infection after the age of 40 years, male sex, excessive alcohol
      consumption, HBV or HIV co-infection and the immunosuppressive state have been
      identified as factors associated with progression of fibrosis and development of
      cirrhosis. The relationship between virus load, HCV genotype I and quasispecies
      variability and progression of live disease is controversial. In the present
      study on 141 patients with chronic HCV infection and established chronic liver
      disease, the median time to develop cirrhosis was 20 years. Progression to
      cirrhosis was faster (16 vs 20 years) in those who acquired infection after the
      age of 35 years, and in immunosuppressed patients (8 vs 21 years), whereas
      diabetes, sex and HBV co-infection were not associated with faster progression.

PMID- 10921392
TI  - Natural history of chronic hepatitis C.
AB  - The natural history of chronic hepatitis C is one of a slow progression from
      early stage chronic hepatitis without fibrosis to cirrhosis or hepatocellular
      carcinoma (HCC). The disease progresses to advanced stage chronic hepatitis C
      over 10-30 years. Data from Japan indicate that mortality associated with chronic
      hepatitis C results mainly from the development of HCC. We studied 186 patients
      referred between 1968 and 1994. The mean follow-up interval was 8.6 (2-23) years.
      HCC developed in 34 patients (18%). The cumulative probability of HCC development
      was 4% at 5 years, 18% at 10 years and 45% at 15 years. Univariable analysis
      indicated that age at entry, fibrosis stage, inflammation activity and the status
      of IFN treatment (treated vs untreated) were predictive risk factors for
      developing HCC in patients with chronic hepatitis C. Multivariable analysis of
      these risk factors indicated that age at entry (> 50 vs < 50; Risk Ratio = 3.2,
      P< 0.005) and fibrosis stage (F3 vs F0; Risk Ratio= 5.6, P< 0.005) are
      independent risk factors for HCC. From these results it was concluded that (1)
      20% of patients referred to liver clinics with chronic hepatitis C in Japan can
      be expected to develop HCC over a 10 year period; (2) the risk of HCC increases
      with progression of liver fibrosis (F3, F4) and age (greater than 50 years old)
      at the time of diagnosis and (3) the degree of liver fibrosis is a critical
      predictive factor for the occurrence of HCC.

PMID- 10921393
TI  - Case selection for interferon treatment of hepatitis C.
AB  - To establish a case selection algorithm for the treatment of hepatitis C,
      predictive factors were studied and reported articles were reviewed and analysed.
      Because of the relatively poor efficacy of interferon (IFN) monotherapy, which is
      ineffective in 60-70% of patients, case selection at present is determined by the
      likelihood of attaining a sustained response (SR; defined by normalizing serum
      ALT and eliminating serum HCV RNA after treatment) to therapy. According to the
      present study, viral load and genotype, and IL-10 and IL-1ra serum levels, are
      the most predictive of achieving SR after IFN monotherapy given in a
      comparatively high dose regimen for 6 months. In addition, reported studies with
      logistic analyses were carefully reviewed and analysed for the most effective
      predictive factors of case selection. The results again indicated that viral load
      and HCV-genotype (serotype). were closely related to SR. Age, gender, and
      histological changes at treatment were also considered for case selection. These
      results, however, relate solely to IFN-monotherapy. Future development of more
      effective strategies for treating hepatitis C could alter the exclusion criteria
      for IFN treatment and will negate the need for the case selection algorithm
      discussed here.

PMID- 10921394
TI  - Where does treatment fit into the strategy to control hepatitis C?
AB  - The prevalence of hepatitis C varies greatly between countries of the Asia
      Pacific region. The incidence of new cases is also markedly different between
      countries, particularly related to the prevalence of injecting drug use. Overall,
      the currently available treatments for hepatitis C are unlikely to have a major
      impact in the control of the infection from a population perspective while
      success rates are relatively low (20-45% sustained antiviral response) and
      treatment costs are high. There are some specific situations, such as reducing
      the incidence of mother-to-baby transmission or sexual transmission, where
      antiviral treatment can be used as a strategy to prevent further infection. The
      major aims of prevention of hepatitis C infection should lie with public health
      measures to prevent new infections, particularly amongst injecting drug users,
      and ultimately the development of an effective vaccine..

PMID- 10921395
TI  - Consensus among consensus conferences on management of hepatitis C: what we knew
      then and are still sure about, what we are newly sure about, and what we still
      need to know.

PMID- 10921396
TI  - Firstline treatment for hepatitis C: combination interferon/ribavirin versus
      interferon monotherapy.
AB  - In the initial treatment of chronic hepatitis C, interferon-alfa (IFN-alpha)
      monotherapy for 24-48 weeks induces sustained response rates of only 10-20%.
      Combination therapy with IFN-alpha plus ribavirin induces a sustained response in
      40-50% of patients, and can be now recommended as the firstline therapy for
      chronic hepatitis C. Stopping therapy at week 12 because of persistent viraemia
      is unnecessary with the combination therapy because later clearance of HCV RNA
      can still occur with a sustained response. Patients with HCV genotype 1 should
      receive 48 weeks of combination therapy, in contrast to 24 weeks for patients
      with genotypes 2 or 3. For patients who cannot tolerate the side effects of
      ribavirin, such as anaemia, IFN-alpha at 3 MU three times weekly for 48 weeks is
      preferred as the initial therapy. The long-acting pegylated IFN can be expected
      to enhance the efficacy of combination therapy in the treatment of chronic
      hepatitis C and appears to be much more potent as monotherapy. Further studies
      are needed to improve the current 'half-full' status of chronic hepatitis C
      treatment.

PMID- 10921397
TI  - Long-term effects of interferon therapy on histology and development of
      hepatocellular carcinoma in hepatitis C.
AB  - Chronic hepatitis C is a common disease that slowly progresses to cirrhosis and
      eventually to hepatocellular carcinoma (HCC). Histology offers an important
      insight into disease prognosis and treatment response. Biochemical and
      virological responses to interferon (IFN) therapy are associated with an
      improvement in liver histology during and shortly after treatment, but the impact
      of treatment on the history of a slowly progressive disease cannot be ascertained
      by evaluating results at the completion of treatment. Some recent studies showed
      that the severity of hepatic inflammation may be a major factor driving
      progression of chronic hepatitis C to cirrhosis, and that improving hepatic
      inflammation may be associated with regression or retardation of fibrosis,
      especially in patients with virological sustained response. Many recent studies
      have shown an inhibition of the development of decompensation and HCC after IFN
      therapy, but a randomized controlled study using a large number of subjects with
      a more than 5-year observation period will be required to elucidate the exact
      role of antiviral therapy for the delay of decompensation or suppression of HCC.

PMID- 10921398
TI  - Predictors of the efficacy of interferon therapy for patients with chronic
      hepatitis C before and during therapy: how does this modify the treatment course?
AB  - Antiviral therapy for hepatitis C virus (HCV) infection should be based on the
      natural history of HCV infection; there is a sequential, but slow, progression
      from chronic hepatitis to cirrhosis, leading to death from either liver failure
      or hepatocellular carcinoma (HCC). The risk of HCC development increases in
      association with the advance of fibrosis, and antiviral therapy can reduce this
      risk. More than 30 indices have been proposed as 'predictors' of favourable
      response to IFN therapy: host factors (age, gender, duration of HCV-infection,
      alcohol intake, hepatic iron stores, platelet count, histological staging of the
      liver disease), viral factors (HCV RNA levels in serum, HCV subtype, diversity of
      the hypervariable region, mutation of non-structure 5A gene), and IFN factors
      (dose, duration of treatment, type, treatment regimens i.e. every day vs three
      times a week, escalating dose regimen). Before starting IFN therapy, HCV subtype
      and pretreatment HCV RNA load, as well as the fibrotic stage of the liver, should
      be determined. The response to IFN therapy should be monitored by the HCV RNA
      status in serum during therapy, and the treatment regimen modified, or
      discontinued as required. A sustained virological response should be checked at
      more than 3 months after the completion of therapy. Even though the risk of HCC
      is markedly reduced in sustained responders, it is possible to develop HCC
      several years after completion of IFN therapy.

PMID- 10921399
TI  - Hepatitis C: retreatment and treatment of patients with renal failure.
AB  - This paper addresses two difficult issues in the treatment of hepatitis C:
      patients who fail to achieve a sustained response after the first course of
      treatment, and those who simultaneously suffer from chronic renal failure. With
      the recent improvements in firstline treatment, retreatment is mainly applicable
      to those who have previously received 6-month of interferon monotherapy at 3 MU
      thrice weekly. For those who had an end-of-treatment response but relapsed, there
      is a choice between interferon monotherapy at increased dose and/or duration of
      treatment, or a 6-month course of combination therapy. Retreatment of non
      responders is generally unsuccessful, but some patients may respond to interferon
      alpha 3 MU and ribavirin 1.0-1.2 g/day. For patients with chronic renal failure
      and hepatitis C, combination treatment is not possible because ribavirin is
      contraindicated. Interferon given at a dose of 1.5 MU thrice weekly was reported
      to be fairly well tolerated by patients who were on dialysis and resulted in end
      of-treatment and sustained biochemical and virological response in some cases.
      Interferon given in the usual doses may be associated with severe adverse effects
      in patients with renal failure, and can precipitate allograft rejection in
      patients who have undergone renal transplantation.

PMID- 10921400
TI  - Adverse effects and other safety aspects of the hepatitis C antivirals.
AB  - The preferred treatment for patients with chronic hepatitis C, either treatment
      naive, relapsers or nonresponders to IFN monotherapy, is now IFN-ribavirin
      combination treatment. The adverse effects of IFN are well established and
      familiar to hepatologists all over the world. More than 25,000 patients worldwide
      have been treated with combination therapy. Patients re-treated with a
      combination regimen are more likely to tolerate IFN better than treatment-naive
      patients, probably due to better case selection. The safety profile of regimens
      containing IFN-alpha plus ribavirin is generally consistent with the safety
      profile of each agent when employed in monotherapy; there is little or no
      synergistic toxicity. Anorexia, dyspnoea, cough, pruritus and rash are the only
      adverse events reported at a consistently higher frequency with combination
      treatment, and are usually mild to moderate in severity and rarely result in dose
      reductions or discontinuation. The primary cause of dose reduction for
      combination therapy is haemolytic anaemia, which can be managed effectively. The
      most common reason for discontinuation of therapy for either type of therapy is
      psychiatric problems, especially depression, which seems to be closely related to
      the duration of treatment. In patients receiving combination therapy, anaemia and
      depression need close monitoring, and dose modification in some cases. Strict
      guidelines for dose reduction and discontinuation are essential to prevent
      serious adverse events. Because of the teratogenic risk from ribavirin, pregnancy
      is contraindicated in patients or their partners during and 6 months after
      treatment.

PMID- 10921401
TI  - What should we advise about adjunctive therapies, including herbal medicines, for
      hepatitis C?

PMID- 10921402
TI  - Liver transplantation in chronic hepatitis B and C.
AB  - The general indications for liver transplantation in hepatitis B virus (HBV) and
      hepatitis C virus (HCV) infection, and the issues surrounding treatment for HBV
      infection in the pre- and post-transplant periods, are discussed. In general,
      transplantation is reserved for patients with end-stage liver failure secondary
      to cirrhosis and a small population with acute liver failure. It is proposed that
      certain guidelines can be developed and that these should include any one of the
      following: a Child-Pugh score > or = 9, diuretic resistant ascites, recurrent
      portal hypertensive bleeding, recurrent encephalopathy, spontaneous bacterial
      peritonitis and the development of a small hepatocellular cancer (< or = 5 cm in
      diameter). Treatment for HBV infection now includes lamivudine therapy pre and
      post transplantation together with hepatitis B immunoglobulin. Such an approach
      has virtually abolished recurrence of HBV infection following liver
      transplantation.

PMID- 10921403
TI  - Indications and needs for living-related transplantation in adults.

PMID- 10921404
TI  - Fulminant hepatitis B in patients with chronic HBV infection.

PMID- 10921405
TI  - Indications for liver transplantation in patients with chronic hepatitis B and C
      virus infection and hepatocellular carcinoma.
AB  - Patients with chronic hepatitis B virus (HBV) infection were not accepted for
      liver transplantation in Asia in the past because the hepatitis B immune globulin
      (HBIG) used to prevent post-transplantation recurrence was very expensive and it
      was generally believed that Asians with hepatitis B fared worse than Caucasians
      after liver transplantation. The availability of lamivudine has altered the
      indication of liver transplantation for these patients. Twenty-five Chinese
      patients with chronic HBV infection were given lamivudine as primary prophylaxis
      against HBV re-infection before transplantation. Five patients died within 40
      days of transplantation. After a median follow-up period of 14 months (range, 5
      39), 17 patients had lost serum HBsAg from 4 days to 27 months post
      transplantation, but it reappeared in three patients 4-12 months later. Antibody
      to HBsAg was detected periodically in the serum of 1 patients who had lost HBsAg.
      At the last follow-up, six patients were HBsAg-positive and HBV DNA was detected
      in only one of them. The indication for liver transplantation for chronic
      hepatitis C virus (HCV) infection is not as strict as for patients with chronic
      HBV infection because the long-term survival is similar to that of non-hepatitis
      C patients, even though re-infection by HCV in the recipients is nearly
      universal. The main issue in the selection of patients with HCV for liver
      transplantation is therefore identification of criteria that can predict re
      infection and development of cirrhosis. These include factors such as multiple
      episodes of rejection, use of OKT3, pre-transplant viral load and genotype, but
      reports are not consistent and so there are no well-defined selection criteria.
      The selection criteria for patients with hepatocellular carcinoma are now well
      defined. Many studies have confirmed that a tumour > 5 cm, and showing vascular
      invasion, and poor differentiation adversely affects survival. In practice, only
      patients with a tumour < 5 cm and Child's C cirrhosis are accepted for liver
      transplantation. Transarterial oily chemoembolization and intralesional alcohol
      injection are used to control or down-stage the tumour while patients wait for a
      cadaveric liver graft.

PMID- 10921406
TI  - Pre- and post-transplant treatment of hepatitis C.

PMID- 10921407
TI  - Role of endoscopic retrograde cholangiopancreatography in late biliary tract
      complications after orthotopic liver transplantation.

PMID- 10921408
TI  - Thrombopoietin and liver diseases.

PMID- 10921409
TI  - Treatment of hepatitis C with interferon and ribavirin.
AB  - Hepatitis C is a worldwide problem that frequently results in end-stage liver
      disease and its complications. Treatment for hepatitis C virus (HCV) has been
      rather ineffective but several recent studies have clarified the role of
      interferon and ribavirin therapy. In line with therapeutic progress in HIV
      infection, hepatitis C is now entering the era of multidrug antiviral therapy.
      Ribavirin is an orally active synthetic guanosine analogue with theoretical
      antiviral and immunomodulatory actions. In this review we have evaluated the role
      of interferon and ribavirin in treatment-naive patients, relapsers and non
      responders. In naive patients the combination results in improved end-of
      treatment and sustained response rates, with an overall 41% sustained virological
      response rate in patients treated for 48 weeks. Therapeutic benefit also extends
      to the traditionally difficult to treat patients (genotype 1, high vital load and
      advanced fibrosis). The addition of ribavirin to interferon has also resulted in
      an increased toxicity profile, which has made therapy more difficult for both the
      patient and managing physician. However, the significant improvement in response
      rates for all patients makes combination therapy the most appropriate choice as
      the first-line therapy for suitable patients with chronic viral hepatitis C.
      Appropriate management with interferon and ribavirin includes assessing the
      patient's HCV genotype to determine the optimal duration of therapy, assessing
      therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the
      additional ribavirin side-effects.

PMID- 10921410
TI  - Hepatic resection for benign tumours of the liver.
AB  - The most frequent benign tumours of the liver include haemangioma, liver cell
      adenoma and focal nodular hyperplasia. Patients may undergo hepatic resection
      because of a preoperative diagnosis of malignancy or uncertainty in diagnosis
      despite an extensive work-up.

PMID- 10921411
TI  - Diagnosis and treatment of gastro-oesophageal reflux disease in infants and
      children.
AB  - Gastro-oesophageal reflux is a frequent, aspecific phenomenon in infants and
      children. The recommended approach in infants with uncomplicated regurgitation
      consists of reassurance of the parents and, if this fails, dietary
      recommendations in formula-fed infants. If, despite these efforts, symptoms
      persist, administration of prokinetics, such as cisapride, is recommended prior
      to investigations such as oesophageal pH monitoring. Oesophageal pH monitoring is
      also recommended to document gastro-oesophageal reflux disease in children with
      unusual presentations such as chronic respiratory disease. Today, cisapride is
      the drug of choice because it has the best efficacy and safety profile. In
      infants and children presenting with symptoms suggesting oesophagitis, endoscopy
      of the upper gastrointestinal tract is recommended. If there is severe
      oesophagitis, acid suppression with histamine H2-receptor antagonists or proton
      pump inhibitors in combination with prokinetics, are recommended. In life
      threatening situations, or in patients that are resistant to or dependent on acid
      suppressive medication, a surgical procedure such as laparascopic Nissen
      procedure should be considered.

PMID- 10921412
TI  - Elevation of TFF1 gene expression during healing of gastric ulcer at non
      ulcerated sites in the stomach: semiquantification using the single tube method
      of polymerase chain reaction.
AB  - BACKGROUND: The Trefoil factor family 1 (TFF1), one of the trefoil peptides, has
      been considered to play protective and reparative roles of experimentally induced
      ulcers in the stomach. However, the alteration of the TFF1 mRNA in the non
      ulcerated areas of living human gastric mucosa in gastric ulcer is not well
      known. We examined TFF1 gene expression at non-ulcerated sites during the healing
      of a gastric ulcer by semiquantitative determination of the TFF1 mRNA. METHODS:
      Gastric mucosal biopsy specimens were taken before and after the healing of the
      gastric ulcer from seven consecutive patients and from seven patients diagnosed
      with non-ulcer dyspepsia (NUD). The relative value of TFF1 mRNA (RTFF1) was
      calculated by the single tube method of polymerase chain reaction (ST-PCR) and
      Southern hybridization. Immunohistochemistry using monoclonal antibodies was
      performed to confirm the presence of the TFF1 peptide. The status of Helicobacter
      pylori and the severity of gastritis were investigated simultaneously. RESULTS:
      The mean relative values of TFF1 mRNA at both the gastric angle (RTFF1AS) and the
      gastric body (RTFF1BS) of patients with gastric ulcers at the healed stage were
      significantly higher than those at the open stage (P< 0.05). The mean RTFF1AS at
      both the open and healed stages were lower than those of RTFF1BS at the open and
      healed stages, respectively, The mean RTFF1B at the open stage was lower than
      that in NUD (not significant), but the mean of RTFF1B at the healed stage was
      significantly higher than that in NUD. The RTFF1AS and RTFF1BS of all patients
      did not correlate with H. pylori status nor with the severity of gastritis. The
      induction of TFF1 mRNA at the non-ulcerated background sites seemed not to be
      related to the status of H. pylori or to the severity of gastritis. CONCLUSIONS:
      These results suggest that the increased levels TFF1 mRNA during the healing of
      gastric ulcers might be closely related to the protection and the cell
      differentiation at the non-ulcerated areas of living human gastric mucosa.

PMID- 10921413
TI  - Duodenal ulcer prevalence: experimental evidence for the possible role of dietary
      lipids.
AB  - BACKGROUND AND AIMS: Mapping the geographical distribution of duodenal ulcer in
      relation to staple diets, and experiments on animal peptic ulcer models suggested
      that the lipid fraction in certain foodstuffs had a protective effect which was
      most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid
      obtained from stored polished rice or rice bran was ulcerogenic. Further animal
      experiments were designed to investigate the protective and healing effects of
      Horse gram lipid (HGL) against peptic ulceration. METHODS: Three effects were
      investigated in rats: (i) the protective effect of HGL on peptic ulceration
      produced by using pyloric ligation in combination with South Indian diet or rice
      bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast
      cell degranulation in response to pyloric ligation and rice bran oil; and (iii)
      the healing effect of HGL on acute gastric ulceration produced by alcohol, on
      chronic gastric ulceration produced by topical acetic acid or on chronic duodenal
      ulcer following cysteamine. RESULTS: Horse gram lipid was shown to be protective
      and to promote ulcer healing in all the models used. Mast cell degranulation was
      inhibited. CONCLUSION: The experiments confirm the presence of a lipid in certain
      staple foods that have protective and healing properties in experimental peptic
      ulcer animal models. The differences in the prevalence of duodenal ulceration
      between different regions in some developing countries with a high prevalence of
      Helicobacter pylori infection might be explained by the presence or absence of
      protective lipids or ulcerogenic factors in the staple diet.

PMID- 10921414
TI  - Modified rapid urease test for Helicobacter pylori detection in relation to an
      immunohistochemical stain.
AB  - BACKGROUND: The rapid urease test and touch cytology have been used for the rapid
      detection of Helicobacter pylori infection. Recently, a modified rapid urease
      (MRU) test, which provides results in 20 min has been available on a commercial
      basis. To date, few reports have evaluated the accuracy of this test. This study
      evaluated the sensitivity, specificity, and accuracy of the MRU test and touch
      cytology to detect H. pylori in relation to the density of H. pylori infection
      determined semi-quantitatively by using immunohistochemical stains. METHODS:
      Biopsy specimens obtained from a total of 60 patients who underwent endoscopy for
      evaluation of gastroduodenal diseases were studied by using the MRU test, Giemsa
      stain for touch smear tissue and histological methods. An immunohistochemical
      stain was used as a standard, and the density of H. pylori infection was graded
      according to the number of individual bacteria seen as follows: grade 0 = 0;
      grade 1+ = 1-9; grade 2+ = 10-29; grade 3+ = 30-99; grade 4+ > or = 100. The
      severity of gastritis was evaluated histologically in each specimen and compared
      with the density of H. pylori infection. RESULTS: The MRU test had an overall
      sensitivity of 73%, specificity of 100% and accuracy of 85%. The Giemsa stain had
      a sensitivity of 91%, specificity of 100% and accuracy of 95%.The sensitivities
      of the MRU test and Giemsa stain decreased in mild H. pylori infection. In the
      MRU test, the sensitivity was 47% when the density of H. pylori infection was 1+,
      while 80-100% sensitivities were obtained when the densities of infection were >
      or = 2+. With the Giemsa stain, the sensitivity was 80% when the density was 1+,
      while the sensitivity increased to 100% when the densities were > or = 2+. The
      severity of gastritis determined by the Rauws scores showed a positive
      correlation with the density of H. pylori infection as evaluated by
      immunohistochemical staining. CONCLUSIONS: The MRU test had high sensitivity and
      specificity for moderate to severe H. pylori infection, but it may result in
      false-negative results in tests for mild infection. As the MRU test has the
      advantages of shorter incubation times and low cost, a combination of the MRU
      test and the Giemsa stain for touch cytology may be the most time- and cost
      efficient tests in a clinical setting for the diagnosis of H. pylori infection.

PMID- 10921415
TI  - Racial differences in the prevalence of ulcerative colitis and Crohn's disease in
      Singapore.
AB  - BACKGROUND: The aim of this study was to determine the prevalence rates of
      inflammatory bowel disease in the different races in Singapore. METHODS: The
      patients studied consisted of 58 people with an established diagnosis of
      ulcerative colitis (UC) and Crohn's disease (CD) as determined by a combination
      of clinical, radiological, endoscopic and histological criteria. The patients
      were residents of a well-defined geographical area in the northern part of
      Singapore and had been referred to the single regional hospital. Epidemiological
      data including sex, age, ethnicity, family history and disease type and extent
      were collected from case records and patient interviews. RESULTS: There were 37
      UC and 21 CD patients. Of the patients with UC, 67.5% were Chinese, 13.5% were
      Malay and 19% were Indian. The CD group consisted of 81% Chinese, 9.5% Malay and
      9.5% Indian patients. The study population from which the patients were drawn was
      approximately 0.5 million in size. CONCLUSIONS: The overall prevalence of UC was
      6 per 100,000 and of CD was 3.6 per 100,000 in Singapore. There were
      disproportionately more Indians suffering from UC, with a prevalence of 16.2 per
      100,000 in comparison with six per 100,000 for Chinese and seven per 100 000 for
      Malays. The relative risk of UC in Indians is 2.9-fold greater than for the
      Chinese (CI= 1.25-6.7) which was statistically significant. This trend was not
      seen for CD.

PMID- 10921416
TI  - Polyunsaturated fatty acids reduce non-receptor-mediated transcellular permeation
      of protein across a model of intestinal epithelium in vitro.
AB  - BACKGROUND: Dietary polyunsaturated fatty acids influence the natural history of
      intestinal inflammatory diseases. Varying the types of long-chain fatty acids
      that are exposed to cells alters the physicochemical properties of cell
      membranes. This study aimed to determine whether such variations alter
      transcellular and paracellular permeability in intestinal epithelium. METHODS:
      Monolayers of Caco-2 cells, allowed to differentiate by culturing for 7 days
      following confluence, were used as the model for intestinal epithelium.
      Paracellular permeability was assessed by measurement of transepithelial
      resistance, while transcellular permeability was assessed by the transepithelial
      flux of horseradish peroxidase. RESULTS: Exposure of the cells to 100 micromol/L
      of palmitic acid, oleic acid, eicosapentaenoic acid, or linoleic acid, was not
      toxic to cells (measured by leakage of lactate dehydrogenase), and altered cell
      membrane fatty acid composition (as measured by gas chromatography). Flux of
      horseradish peroxidase was significantly affected by 24 h fatty acid exposure (P=
      0.038, ANOVA), being decreased by 23 +/- 6% (mean +/- SEM) by eicosapentaenoic
      acid and 25 +/- 3% by linoleic acid. Oleic acid, palmitic acid and butyrate, had
      no effect. Transepithelial resistance also varied significantly across the
      treatment groups (P< 0.001) due to a 28 +/- 5% increase induced by butyrate. The
      long-chain fatty acids had no effect. CONCLUSIONS: Both omega-3 and omega-6
      polyunsaturated fatty acids reduce transcellular, non-receptor-mediated
      permeation of proteins across differentiated Caco2 cell monolayers, without
      altering paracellular permeability. Alteration of intestinal barrier function
      should be considered as a possible mechanism of action of dietary polyunsaturated
      fatty acids.

PMID- 10921417
TI  - Influence of RNA titre and amino acid changes in the NS5A region of GB virus
      c/hepatitis G virus on the effectiveness of interferon therapy.
AB  - BACKGROUND: A relationship between the pretreatment RNA titre of GB virus
      C/hepatitis G virus (GBV-C/HGV) and the effectiveness of interferon (IFN) therapy
      has been reported previously. However, the influence of changes in the amino acid
      sequence of the NS5A region of GBV-C/HGV on the effectiveness of IFN therapy has
      not been examined, although this influence has been explored in patients with
      chronic hepatitis caused by hepatitis C virus. We examined the relationship
      between changes in the amino-acid sequence of the NS5A region and the
      effectiveness of IFN therapy. METHODS: The subjects were 10 patients with chronic
      hepatitis C coinfected with GBV-C/HGV and treated with IFN. The pretreatment
      level of GBV-C/HGV-RNA (copies/mL) in their sera was measured by real-time
      detection polymerase chain reaction (PCR) assay. At 6 months after cessation of
      therapy, four of 10 patients had become negative for GBV-C/HGV-RNA (CR, complete
      response) and six patients were still positive for GBV-C/HGV-RNA (NR, non
      response). We determined the nucleotide sequence of the NS5A region (amino acid
      residues 1865-2279; NS5A1865-2279) of pretreatment GBVC/HGV-RNA by direct
      sequencing. RESULTS: The pretreatment GBV-C/HGV-RNA level of CR patients (7.8 x
      10(4) - 6.2 x 10(5), mean 3.30 x 10(5)) was significantly lower than that of NR
      patients (6.3 x 10(7) - 7.2 x 10(8), mean 3.55 x 10(8); P< 0.01). The number of
      amino acid substitutions in NS5A1865-2279 was five to seven (mean 5.8 +/- 1.0) in
      CR patients, and four to eight (mean 6.8 +/- 1.6) in NR patients, a difference
      that is not significant. Moreover, there were no amino acid substitutions or
      sites of substitution in NS5A1865-2279 that were specific to either group.
      CONCLUSIONS: The effectiveness of IFN therapy for GBV-C/HGV is strongly related
      to the pretreatment GBV-C/HGV-RNA level, but is not related to changes in
      NS5A1865-2279.

PMID- 10921418
TI  - Detection of vascular endothelial growth factor and its receptor expression in
      human hepatocellular carcinoma biopsy specimens.
AB  - BACKGROUND: Vascular endothelial growth factor (VEGF) exerts its actions on the
      microvasculature, by interacting with specific endothelial cell receptors, and
      thus, contributes to angiogenesis and growth in many tumours. METHODS: Using
      nested reverse-transcription-polymerase chain reaction, we examined the biopsy
      specimens of 14 patients with human hepatocellular carcinoma (HCC) and cirrhosis,
      for the expression of hepatic VEGF, and the VEGF receptors KDR and fit-1. To
      avoid the influence of hypoxia or ischaemia induced by surgical manipulation, we
      used biopsy specimens of the liver instead of resected specimens. RESULTS:
      Vascular endothelial growth factor mRNA expression was detected in the tumour
      portion of the specimens in 13 of 14 patients (93%), and in the corresponding non
      tumour portion of the specimens in eight patients (57%; P= 0.08). No differences
      were found between the tumour portion and the corresponding non-tumour portion in
      relative concentrations of VEGF mRNA. However, mRNA expression of the VEGF
      receptors, KDR and fit-1, was detected in 14 (100%) and 11 (79%) of the tumour
      portions, respectively, and in four (29%) and five (36%) of the corresponding non
      tumour portions, respectively (chi2 test: KDR, P< 0.01; fit-1, P= 0.08). The
      relative concentration of KDR mRNA in the tumour portions was significantly
      higher than in the non-tumour portions (Mann-Whitney U-test: P<0.001) but no
      differences were detected for fit-1. CONCLUSIONS: KDR mRNA is significantly
      overexpressed in HCC lesions and could be associated with the angiogenesis and
      tumour growth induced by VEGF.

PMID- 10921419
TI  - Expression of hepatic thrombopoietin mRNA in primary cultured hepatocytes and in
      rats with acute liver injury or bone marrow suppression with or without
      cirrhosis.
AB  - BACKGROUND AND AIMS: The main causes of thrombocytopenia in cirrhosis are thought
      to be platelet destruction and the reduction of thrombopoietin (TPO) expression
      in the liver. The mechanisms by which levels of TPO mRNA are regulated in
      cirrhosis have not been elucidated. In this study, we investigated some possible
      mechanisms. METHODS: We used three experimental models: bone marrow suppression,
      acute liver injury and primary cultured hepatocytes. We used northern blots to
      assess the kinetics of TPO mRNA expression in the livers of irradiated rats (with
      and without cirrhosis) in acute liver injury and in primary cultured hepatocytes
      treated with hepatotoxin or cytokines. RESULTS: Although the bone marrow was
      hypocellular, there was no apparent enhancement of TPO mRNA expression in the
      irradiated rats with cirrhotic livers compared with the unirradiated rats with
      cirrhotic livers. There were no conspicuous changes in hepatic TPO mRNA
      expression between the livers of the control rats and the three models of acute
      liver injury. There were no conspicuous changes in the levels of TPO mRNA between
      control hepatocytes and hepatocytes treated with hepatotoxin or cytokines.
      CONCLUSIONS: Our results suggest that bone marrow is not a regulator of hepatic
      TPO production in cirrhosis. The reduced TPO mRNA expression found in cirrhotic
      rats may not result merely from serious cellular damage; it may be associated
      with cirrhosis-specific regulatory mechanisms for the expression of the TPO gene.
      Further studies are needed to search for other factors that may induce reduced
      TPO expression.

PMID- 10921420
TI  - Late biliary tract complications after orthotopic liver transplantation:
      diagnostic and therapeutic role of endoscopic retrograde
      cholangiopancreatography.
AB  - BACKGROUND: Biliary tract complications are frequent after orthotopic liver
      transplantation. Late biliary tract complications occurring after T-tube removal
      mostly include stones and strictures which may be associated with sepsis and
      worsening of the liver function. Endoscopic retrograde cholangiopancreatography
      (ERCP) has a role in the diagnosis and therapy of these complications. The aim of
      our study was to report our experience of endoscopic diagnosis and treatment of
      late biliary tract complications in liver-transplanted patients. METHODS AND
      RESULTS: One hundred and thirty-six adult liver-transplanted patients have been
      followed since 1988. Seventeen patients (12.5%) needed a total of 30 ERCP because
      of evidence of clinical and/or biochemical cholestasis: eight with biliary
      stricture; six with biliary stones; one with both stricture and stones; and two
      with normal ERCP findings. Interventional endoscopic procedures included 14
      sphincterotomies, six stone removals, seven biliary balloon dilatations, seven
      biliary stent placements, 11 biliary stent replacements, seven nasobiliary
      catheter placements and one mechanical lithotripsy. No complications were seen.
      In all cases, ERCP was able to identify the location, entity and dimension of the
      late biliary tract complication, thus allowing a therapeutic strategy to be used.
      Two patients had medical cholestasis. Forty-seven per cent of patients with late
      biliary tract complications could definitely be cured by ERCP alone. The ERCP
      improved the patients' condition to allow subsequent surgery in five patients
      (33%). CONCLUSIONS: These results confirms that ERCP is a valuable diagnostic
      tool and should be considered as the first step in the non-surgical management of
      late biliary tract complications after orthotopic liver transplantation.

PMID- 10921422
TI  - Iron excretion in iron-overloaded rats following the change from an iron-loaded
      to an iron-deficient diet.
AB  - BACKGROUND: Iron stores in the body are thought to be regulated by a mechanism
      associated with the rate of iron absorption from the diet, with no significant
      role played by iron excretion. We report the existence of an iron excretory
      process that results in the loss of significant amounts of liver iron. METHODS
      AND RESULTS: Rats were fed 3% carbonyl iron for 9 weeks, which resulted in a 20
      fold increase in liver non-haem iron. When the rats on this iron-loaded diet were
      switched to a low iron diet for 2 and 7 days, liver non-haem iron levels fell 30%
      and 45%, respectively. A similar fall in transferrin-bound plasma iron was also
      seen. As the liver iron had not redistributed to other body compartments, it was
      concluded that the iron had been excreted and that the excreted iron represented
      a loss of 22% and 28% in total body non-haem iron over 2 and 7 days,
      respectively. Ligation of the common bile duct in iron loaded rats that had been
      switched to the iron-deficient diet was accompanied by a similar loss of liver
      iron and also hepatocellular damage. In addition, measurement of enterocyte iron
      levels showed that only approximately 5% of the total iron excreted was found in
      these cells. CONCLUSION: Neither bile nor enterocytes play a significant role in
      iron excretion. The similarity in the degree of fall in transferrin-bound iron
      levels with a change in diet suggests that iron excretion involves the uptake and
      excretion of transferrin bound-iron, possibly by goblet cells. The observed
      hypertrophy of the intestinal mucosa associated with carbonyl iron feeding may
      facilitate hypersecretion of mucous and the excretion of this iron.

PMID- 10921421
TI  - Recurrence of biliary symptoms after endoscopic sphincterotomy for
      choledocholithiasis in patients with gall bladder stones.
AB  - BACKGROUND: There are a few reports regarding the long-term results of endoscopic
      sphincterotomy (EST). However, little data is available on the recurrence of
      biliary symptoms after EST for choledocholithiasis, in patients with gall bladder
      stones. METHODS: All patients had gall bladder and common bile duct stones (n =
      60; age 32-84 years, median age 55 years), and had received an EST. One group of
      these patients had a laparoscopic or open cholecystectomy (n = 39; group A),
      while the other group did not (n = 21; group B). The follow-up- period ranged
      from 5 to 54 months (average 22 months). RESULTS: Complications included the
      recurrence of common bile duct stones, recurrent acute cholecystitis,
      postoperative bile leakage and papillary stenosis. Nine patients (15%) had a
      recurrence of biliary symptoms. Two significant prognostic factors for the
      recurrence of biliary symptoms were identified by multivariate analysis; namely
      an intact gall bladder and a dilated common bile duct. The recurrence rate of
      biliary symptoms in group B was 20.4%, while in group A it was 10.3% (P< 0.01).
      Patients with a larger than average common bile duct diameter (mean diameter 14
      mm) were more prone to the recurrence of symptoms than those with a smaller
      common bile duct diameter (mean diameter 10 mm, P< 0.016). The hospital stay
      period was 8.9 +/- 3.1 days in group A and 2.8 +/- 1.9 days in group B (P< 0.01).
      CONCLUSIONS: Biliary symptom recurrence occurred in a considerable proportion of
      patients after EST for the treatment of choledocholithiasis, in patients with
      gall bladder stones. The prognostic factors associated with the recurrence of
      biliary symptoms were an intact gall bladder and a dilated common bile duct
      diameter. Regardless of their short stay in hospital, non-cholecystectomy
      patients had a higher rate of recurrent biliary symptoms than cholecystectomy
      patients.

PMID- 10921423
TI  - Hepatobiliary and pancreatic: a man with ascites.

PMID- 10921424
TI  - Gastrointestinal: Helicobacter pylori gastritis.

PMID- 10921425
TI  - Temporary use of an accuflex stent for unextractable common bile duct stones.
AB  - Endoscopic management has become the main therapeutic approach for the extraction
      of common bile duct (CBD) stones, and successful removal can be achieved in 80
      90% patients using conventional balloon and basket techniques. However, if it is
      difficult to completely fragment a stone, or to clear the CBD, which may occur
      for a variety of reasons, the therapeutic problem will remain. When bile duct
      stones can not be removed, a viable management option is to place a biliary stent
      to ensure drainage. However, recent studies of long-term biliary stenting, with a
      plastic stent, showed a relatively high rate of morbidity and mortality. We
      report an alternative, unique treatment for unextractable common bile duct
      stones, using the temporal placement of an expandable metallic stent (EMS) to
      facilitate passage of fragments through the papilla.

PMID- 10921426
TI  - Life-threatening haemorrhage from a sternal metastatic hepatocellular carcinoma.
AB  - Rupture of the tumour is a catastrophic complication of hepatocellular carcinoma.
      The prognosis in patients with a ruptured hepatocellular carcinoma is usually
      unfavourable. We describe a 46-year-old man who suffered from visible massive
      tumour haemorrhage due to a hepatitis B-related hepatocellular carcinoma that
      metastasized to the sternal bone. The prominent tumour mass was bulging over the
      anterior chest wall on the sternum of the patient, and bled spontaneously. This
      episode of life-threatening haemorrhage was stopped by surgical ligation of the
      bleeding site. Palliative radiotherapy shrank the tumour mass size and prevented
      further possible bleeding. This is likely to be the first reported case with a
      visible spontaneous tumour bleeding from a sternal metastatic hepatocellular
      carcinoma.

PMID- 10921428
TI  - An etiologic model of alcoholism from a developmental ecological perspective.
AB  - To reflect the complexity of alcoholism and the heterogeneity of the alcoholic
      population, an etiologic model should integrate biological, psychological, and
      environmental factors. The model proposed here does so, postulating that "risk"
      for alcoholism fluctuates throughout the lifespan of an individual. In addition,
      this developmental ecological model takes into account both the imputed risk and
      the protective factors, makes possible a more detailed analysis for each life
      stage of an individual, and remains flexible enough to accommodate forthcoming
      empirical data.

PMID- 10921427
TI  - Haemorrhagic cerebral sinus thrombosis associated with ulcerative colitis: a case
      report of successful treatment by anticoagulant therapy.
AB  - A 29-year-old man with ulcerative colitis was admitted to our hospital because of
      convulsions and a headache. Before admission, oral prednisolone had been
      administered due to his ulcerative colitis relapse. Computed tomography revealed
      a low-density area in the right frontal pole suggestive of a venous infarction.
      Once his headache and convulsions improved after the administration of an
      antiepileptic drug, he began to complain of right arm numbness and right
      hemianopsia again. An urgent magnetic resonance imaging angiograph showed
      extensive thrombosis in the superior sagittal sinus. We finally used the
      anticoagulant agents, heparin and urokinase, which eased his complaints and
      prevented the development of bloody stools. He was discharged with no
      neurological symptoms 25 days after admission. This is a rare case of sinus
      thrombosis complicated by ulcerative colitis, in which anticoagulant therapy was
      successful. Magnetic resonance imaging angiography was useful for the diagnosis
      and for evaluating the therapeutic effect.

PMID- 10921429
TI  - Survival of HIV-1 in syringes: effects of temperature during storage.
AB  - In a previous paper we demonstrated that HIV-1 survival in syringes was strongly
      associated with the volume of blood remaining and with the duration of storage at
      room temperature. The current study was performed to determine the effects of
      storage temperature upon the survival of HIV-1 inside syringes. At 4 degrees C,
      50% of all syringes contained viable HIV-1 at 42 days of storage, the longest
      storage duration tested. At room temperature (20 degrees C), the last day that
      syringes with 2 microL of infected blood were positive was Day 21, and viable HIV
      1 was recovered from 8% of syringes. The last day on which syringes with 20
      microL were positive was Day 42, and viable HIV-1 was recovered from 8% of
      syringes. Above room temperature (27, 32, and 37 degrees C), the likelihood of
      encountering syringes with viable HIV-1 when periods of storage exceeded 1 week
      decreased to less than 1%. The temperatures at which drug injectors are likely to
      store their used syringes will vary according to climate, season, and
      circumstances faced by the injector. The survival of HIV-1 in contaminated
      syringes varied over a range of temperatures, and this may be a factor
      influencing the syringe-borne transmission of HIV-1.

PMID- 10921430
TI  - Age and HIV risk in a national sample of injection drug and crack cocaine users.
AB  - A national sample of 25,106 out-of-treatment crack cocaine and injection drug
      users was examined to determine the effect of aging on HIV risk behavior.
      Injectors and crack cocaine users aged 55 and over were compared to those who
      were aged 18 to 54 years of age. Results showed that the behavior risk of older
      persons did not differ substantially from those reported by other age groups, and
      that injection risk rose steadily along with age for all ages represented in the
      sample. The authors conclude that older persons who use illegal drugs remain at
      elevated risk for HIV compared to the general population, and may be in need of
      more targeted intervention strategies.

PMID- 10921431
TI  - "They should have them all over the place": a health program for children of
      illicit drug users.
AB  - A peer-based support and advocacy group for illicit drug users in collaboration
      with a community nurse developed an innovative program for the children of users.
      The program provides well-baby checks, immunization monitoring, parenting advice,
      monitoring of children's safety, a free lunch and education about nutrition, as
      well as activities for the children and mothers. In addition, it allows mothers
      to have time out in a friendly, relaxed, safe, and nonjudgmental environment. The
      program has been running for more than 7 years, costs little, and gives a hard-to
      reach population access to valuable health care.

PMID- 10921432
TI  - Screening instruments for alcohol problems: a comparison of cut points between
      Mexican American and Mexican patients in the emergency room.
AB  - The performance of alcohol use disorder screening instruments (CAGE, BMAST,
      AUDIT, TWEAK) at various cut points were compared between a Mexican American
      emergency room (ER) sample (n = 586) and a sample of ER patients in Mexico (n =
      1,417) using ICD-10 and DSM-IV criteria for alcohol dependence and harmful
      drinking/abuse by gender and injury status. Lowering cut points improved
      instrument performance substantially for females in both samples. Further
      research is needed to explore instrument performance by gender and level of
      acculturation.

PMID- 10921433
TI  - Midproject findings from a study of the National Collegiate Athletic
      Association's policy on smokeless tobacco use.
AB  - In this paper we present midproject findings from a longitudinal survey of 5,000
      male athletes at 56 randomly selected American colleges and universities. The
      study monitors athletes' compliance with and perceptions of the effects of an
      organizational policy that restricts smokeless tobacco (ST) use. In 1996 and
      1997, 77% of users reported that they complied with the policy during
      competition. During the same period there was a significant increase in the
      number of users who complied with policy during practices and of those who
      credited the policy with contributing to a decline in their overall tobacco
      consumption (14% vs 68%, p < .001; 17% vs 23%, p < .01: respectively). The
      findings suggest that organizational policies that regulate ST use can have an
      impact on young adult ST use.

PMID- 10921434
TI  - Similarities of substance use between medical and nursing specialties.
AB  - This paper reviews and compares alcohol and other drug involvement findings in
      two professions, medicine and nursing, by specialty. Health care providers are
      naturally subgrouped by specialty, as this is a major work environment factor.
      The evidence indicates an association exists between practicing in certain
      medical or nursing specialties and substance use. In addition, similarities in
      specialty membership and substance use across medicine and nursing suggests there
      may be common risk factors related to substance use that could be addressed using
      interdisciplinary approaches.

PMID- 10921435
TI  - Alcohol use and correlates of binge drinking among university students on the
      Island of Sardinia, Italy.
AB  - An anonymous questionnaire was administered to a sample of 1,911 students at
      Sardinia's main university during the fall of 1997. The questionnaire assessed
      various behaviors relating to alcohol including its use during or outside meals
      and binge drinking, defined as five or more drinks in a row. A significantly
      higher number of males reported drinking alcohol outside of meals and binge
      drinking than females, and males were also more likely to report impaired driving
      and consequences after drinking alcohol than females. A logistic regression model
      was used to determine correlates of binge drinking using demographics, health
      risk behaviors, and leisure activities. The model confirmed being a male as one
      of the strongest correlates, but also included first drinking alcohol before age
      17, marijuana use, living away from parents, cigarette use, having multiple sex
      partners, and exercising. The results indicate that alcohol use is prevalent
      among university students and is related to the use of other substances. Further
      investigation is warranted with particular attention paid to gender as a
      determinant of use.

PMID- 10921436
TI  - Maternal report of attention deficit hyperactivity disorder symptoms in preschool
      children.
AB  - Two hundred and fifty-three mothers were surveyed regarding attention deficit
      hyperactivity disorder (ADHD) symptoms in their preschool children (aged 2-6
      years). Twenty-four children (9.5%) met DSM-IV criteria (criterion A only) for
      ADHD based solely on parent report. Mean ratings of the three core symptoms of
      ADHD (hyperactivity, impulsivity, and inattentiveness) were in the mid-range on a
      1-7 point scale, with mothers indicating their children were most likely to be
      impulsive. Positive parental endorsement of the 18 individual DSM-IV symptoms of
      ADHD ranged from 4% for 'loses things necessary for tasks', to 28.4% for 'is on
      the go or acts as if driven by a motor'. Males and children of less-educated
      parents were more likely to receive endorsement of ADHD symptoms. There were no
      differences with respect to age of the child or birth order (first vs later
      born). Global ratings of hyperactivity and inattentiveness predicted overall
      ratings of ADHD but when classification rates were examined, high global ratings
      were not predictive of diagnosis. These results lend support to the notion that
      relying solely on parents' verbal reports of isolated ADHD symptoms may lead to
      over-identification of the disorder. Thus, using full DSM-IV diagnostic criteria
      and including standardized behaviour rating scales across multiple informants and
      settings, is recommended.

PMID- 10921437
TI  - Children and the city: a summary of recent environmental psychology research.
AB  - The environmental psychology literature is reviewed as it focuses on children's
      needs and experiences of towns and cities. Children are, we argue, the
      unacknowledged outsiders in the planning and management of urban areas; yet their
      enjoyment of and contribution to these areas is ignored at our peril. We discuss
      the importance of place attachment in the child's developing personal identity;
      and the rich affordances of towns and cities for the child's well-being and
      development, alongside an assessment of the evidence about the social and
      physical dangers that are more frequently stressed in popular discussions: these
      range from strangers and street crime, to traffic and pollution. Other related
      topics reviewed include: children's favourite places and their role in the
      child's self-regulation; the role of exploration of the local area as part of the
      child's widening social and cognitive world; gender differences in patterns of
      exploration, and whether these might be changing; and examples of children's
      involvement at more than a token level in the planning of their communities. The
      role of children as consumers in the local economy, and their use of public
      places, malls and plazas, has often been discussed as if they were inevitably
      socially problematic, and that their presence inevitably led to conflicts with
      adult users: yet we argue for a view of cityscapes which bring the different
      strands of society together. We conclude by discussing those Continental European
      city designs which foster the participation of children in the city's social
      life.

PMID- 10921439
TI  - Crying patterns of Korean infants in institutions.
AB  - This study investigates whether the crying pattern of infants reared in
      institutions is different from those reared at home in the same cultural
      backgrounds. Ninety-five institutional infants and 143 home infants, aged 2-18
      weeks were studied through diaries, recorded by children's care-givers or
      mothers. Results showed that the crying duration of the infants in institutions
      was almost double that of infants at home (86 vs 45 min/day) and contact period
      with the care-givers was half that of home infants (136 vs 279 min/day). In
      addition, the duration of periods when the babies were alone was much longer in
      the institution group (1089 vs 1002 min/day). There was a tendency for both
      groups of institution and home infants to cry more during the evening (from 18.00
      to 24.00 h) but there was no definite peak of crying at any age except the slight
      increase of crying after 12 weeks for the institution group. When compared with
      research on Western infants, the daily crying durations of both institution and
      home infants fall short of those of their Western counterparts. The effect of
      care-giving style on the crying pattern, including physical proximity, is
      discussed.

PMID- 10921438
TI  - Attention to infants in the first year.
AB  - The time spent by 158 infants in contact with their carers at 6, 13, 26 and 52
      weeks was reviewed prospectively. Periods of contact in the categories of (1)
      physical care, (2) holding the crying or sleeping infant, and (3) playing and
      interacting with the infant were recorded using 24-h log diaries completed by the
      mother. The mean total carer contact time over a 24-h day did not change
      significantly in the first year, varying between 6.5 and 73 h. Between 6 and 52
      weeks, time spent by the mother in physical care declined significantly from 207
      to 143 min and in holding the crying or sleeping infant from 61 to 17 min (P <
      0.05 and 0.0001 respectively). There were no significant changes in the amount of
      time spent in playing and interacting with the infant over the first year by the
      mother and father, the time being on average 52.7 and 25.0 min respectively. Play
      and interaction with a non-parental carer increased significantly from 14 to 69
      min (P < 0.0001). Relationships between infant size and holding became weaker as
      the infant became older. Infant gender, socioeconomic status and duration of
      breast-feeding did not influence infant contact time.

PMID- 10921440
TI  - Young school children working together: a measure of individualism/collectivism.
AB  - Co-operation and group working are key aspects of the National Curriculum,
      reinforced by recent moves towards redefining the primary school curriculum with
      a greater emphasis on 'citizenship'. There is little research on individual
      differences between children's preferences for group and individual working or
      young children's abilities to work in, and generalize from, group experiences.
      Furthermore, there are no reliable measures of these factors in children. The
      study reported in this paper was the first stage in research, the overall aim of
      which was to look at individual and group differences in young children working
      cooperatively and competitively in groups and alone. The aim of this study was to
      develop a new measure of individualism/collectivism and the associated factors:
      sociability and altruism. Some 152 children from two primary schools in England
      participated in this study. The mean age of the children was 5 years 5 months
      (range 4 years 11 months to 6 years 9 months). A new measure of
      individualism/collectivism based on instruments for use with adults was
      administered to the participating children. Two stable factors,
      individualism/collectivism and sociability, were identified and were both found
      to be reliable. The importance of the measure as a tool for use with other
      methods for evaluating the effectiveness of group work in classrooms is
      considered.

PMID- 10921441
TI  - Psychosocial impact of an X-linked hereditary disease: a study of Alport syndrome
      patients and family members.
AB  - A nationwide search for patients with Alport syndrome (AS), a hereditary
      nephritis with sensorineural hearing loss and occasional ocular anomalies, was
      performed. As AS is usually transmitted in an X-linked fashion, its form is
      usually severe in male and mild in female patients. Semi-structured interviews
      were conducted with 24 patients with AS and their family members from 17 families
      and 11 pedigrees. The emphasis was on psychosocial stress experienced in everyday
      life, as well as the influence of AS on family relationships, especially mother
      son relationships. Special attention was paid to children's reactions and
      feelings as well as the coping strategies of the family. Denial was the most
      common psychological defence found in our study. We found several cases where AS
      had led to chronic mental suffering. One of the patterns was a combination of
      maternal depression and an overprotective attitude toward an AS-affected son. In
      other instances, depressive symptomatology and anxiety were seen in connection
      with complications and an adverse outcome of the disease. Families with any AS
      manifestations should be encouraged to discuss openly the past histories of
      family members, their fears, feelings of guilt, hopes and expectations. The role
      and empathic attitude of the clinician is crucial in this process. Mildly
      affected mothers who have sons with AS are especially in need of psychological
      support. Professional psychological help should be made available but not given
      routinely.

PMID- 10921442
TI  - Preparing children for venepuncture. The effect of an integrated intervention on
      distress before and during venepuncture.
AB  - Venepuncture for routine blood sampling is a very distressing experience for a
      considerable number of children. Not only do they express high levels of distress
      during venepuncture but also in anticipation of the procedure. Therefore,
      prevention or reduction of distress should focus on both phases of the procedure.
      To this end, three preparation elements were combined: local anaesthesia of the
      skin, provision of sensory and procedural information, and involvement of the
      parent. In order to test the effect of this integrated procedure on the distress
      reactions of young children before as well as during venepuncture, 31 children
      were randomly assigned to one of two conditions: preparation or no preparation.
      Independent raters, who were blind to group assignments, scored segments of the
      videotaped behaviour of the children, according to the Groninger Distress Scale.
      Prepared children displayed significantly less distress before and during
      venepuncture than not-prepared children, regardless of their gender, ethnical
      origin, age, injection history, and the tension of their parent.

PMID- 10921443
TI  - Effects of leptin on the response of rat pituitary-adrenocortical axis to ether
      and cold stresses.
AB  - Leptin is a hormone mainly secreted by the adipose tissue, which acts through
      specific receptors widely distributed in the body tissues, including
      hypothalamopituitary-adrenal axis. We have investigated the effects of a
      subcutaneous bolus injection of 5 nmol/kg leptin on the pituitary-adrenocortical
      function in both normal and ether- or cold-stressed rats. Blood concentrations of
      ACTH, aldosterone and corticosterone were measured by specific RIA 2 or 4 h after
      the leptin injection. Leptin administration to normal rats resulted in
      significant rises in the blood levels of ACTH, aldosterone and corticosterone at
      2 h, but not at 4 h. Ether and cold stresses markedly increased hormonal blood
      concentrations at both 2 and 4 h. Leptin magnified ACTH response to ether stress
      at 2 h, but depressed it at 4 h, and enhanced aldosterone response at 2 h,
      without affecting corticosterone response. Leptin increased ACTH response to cold
      stress at both 2 and 4 h, without altering aldosterone and corticosterone
      responses. In light of these findings, we conclude that: (i) leptin evokes a
      middle transient activation of the pituitary-adrenocortical axis of rats under
      basal conditions; (ii) leptin inhibits the ACTH response to ether stress, but
      magnifies that to cold stress; and (iii) the leptin-evoked changes in the blood
      level of ACTH are not paralleled by significant modifications in the secretory
      activity of the adrenal cortex, which probably undergoes a maximal stimulation
      under stressful conditions.

PMID- 10921444
TI  - Leptin prolonged administration inhibits the growth and glucocorticoid secretion
      of rat adrenal cortex.
AB  - Leptin is an adipose-tissue secreted hormone, that acts to decrease caloric
      intake and to increase energy expenditure. Some of the leptin effects on the
      energy balance are known to be mediated by the hypothalamo-pituitary-adrenal
      (HPA) axis, but the role of this cytokine in the regulation of the growth and
      steroidogenic capacity of adrenal cortex is still controversial. Therefore, the
      present study was designed to explore the long-term effects of native leptin[1
      147] and its biologically active fragment leptin[116-130] (6 daily subcutaneous
      injection of 20 nmol/kg) on the rat HPA axis. Leptin[1-147] and leptin[116-130]
      caused a significant adrenal atrophy, which was mainly due to the decrease in the
      volume of zona fasciculata (ZF) and in the number of its parenchymal cells. Both
      leptins provoked a marked drop in the plasma concentrations of ACTH and
      corticosterone, the main hormone produced by ZF cells. The effects of leptin[116
      130] were more intense than those of leptin[1-147]. Leptin[1-147], but not its
      fragment, evoked a clear-cut rise in the plasma concentration of aldosterone.
      Collectively, these findings indicate that prolonged leptin administration, by
      inhibiting pituitary ACTH release, exerts a potent suppressive action on the
      growth and glucocorticoid secretory capacity of the adrenal cortex in the rat.
      The mechanism(s) underlying the aldosterone secretagogue action of native leptin
      remain(s) to be investigated.

PMID- 10921445
TI  - Short-term effects of intramuscular and transdermal testosterone on bone
      turnover, prostate symptoms, cholesterol, and hematocrit in men over age 70 with
      low testosterone levels.
AB  - The objective of the study was to determine whether short-term testosterone
      administration to older men with low bioavailable testosterone would have any
      immediate adverse effects, especially on the symptoms of benign prostate
      hyperplasia, preliminary to embarking on a long-term study of testosterone
      treatment. Transdermal and intramuscular testosterone were compared to determine
      whether there were any rapid changes in markers of bone formation or resorption
      with either testosterone administration. We undertook a non-randomized trial of 9
      weeks intervention with either intramuscular testosterone, transdermal
      testosterone or neither followed by a 9-week observation period. Twenty-seven men
      over age 70 years with no medical conditions known to affect bone turnover and
      total testosterone levels below 350 ng/dl (normal range 350-1230 ng/dl) or
      bioavailable testosterone levels below 128 ng/dl (normal range 128-430 ng/dl)
      received either testosterone via transdermal patch (TP; two 2.5 mg patches/d),
      intramuscular testosterone enanthate (IM; 200 mg every 3 weeks) or no
      testosterone for 9 weeks of treatment followed by a 9 week observation period.
      Nine men were enrolled in each group. The mean age of the men was 74 +/- 3 years
      (range 70-83 years). While all men receiving testosterone treatment increased
      levels above their own baseline, only 6 of 9 men receiving transdermal
      testosterone achieved bioavailable testosterone levels in the normal range for
      young men. Neither treatment group demonstrated changes in estradiol levels. No
      side effects were reported using the intramuscular testosterone while 5/9 men
      using transdermal testosterone developed a rash. There were no significant
      changes in markers of bone resorption or formation in either testosterone
      treatment group. There were no ill effects on prostate size, symptoms or prostate
      specific antigen level. PSA levels of 1.5 +/- 0.7 ng/dl and 1.6 +/- 0.7 ng/dl in
      the TP and IM groups, respectively. were 2.0 +/- 1.0 ng/dl and 1.8 +/- 0.9 ng/dl
      following treatment. Cholesterol profiles were also not affected by either
      transdermal or intramuscular testosterone. Similarly hemoglobin and hematocrit
      remained unchanged in men receiving either testosterone preparation.

PMID- 10921446
TI  - Hormonal control on enzymes of osmoregulation in a teleost, Anabas testudineus
      (BLOCH): an in vivo and in vitro study.
AB  - Hormonal control of osmoregulation in teleosts is not well understood. Role of
      cGH, oGH, PRL, T3 and insulin on gill Na+,K+-ATPase, Mg2+ and Ca2+ ATPases was
      studied in A. testudineus. Short term administration of cGH, PRL or T3
      significantly increased Na+,K+-ATPase, Mg2+ and Ca2+ ATPases, while oGH
      influenced only Mg2+ ATPase, and insulin stimulated Na+,K+-ATPase. Long-term
      treatment with cGH and PRL also significantly increased Na+,K+-ATPase activity.
      GH had an additive with T3 on stimulating Na+,K+-ATPase activity. In vitro
      addition of cGH and oGH also had definite stimulatory effect on gill Na+,K+
      ATPase except for 2ng oGH. Bromocryptine treatment caused a significant reduction
      on Na+,K+-ATPase activity. Both in vivo and in vitro treatments of cGH and PRL
      independently reversed the action of bromocryptine on Na+,K+-ATPase. Combined
      treatment of cGH+PRL was more prominent in stimulating Na+,K+-ATPase in
      bromocryptine treated fish. Present study reveals that GH, PRL and T3 have
      definite regulatory role on enzymes of osmoregulation in the teleost Anabas
      testudineus.

PMID- 10921447
TI  - Distinct roles of cathepsin K and cathepsin L in osteoclastic bone resorption.
AB  - The role of cathepsin K (CAK), cloned as a novel collagenolytic cysteine protease
      (CCP), cathepsin L (CAL) and cathepsin B (CAB) in bone resorption was
      investigated. In mouse calvarial organ culture medium, CAL, detected in trace
      amounts in control conditions, and CCP activity were increased by stimulants of
      bone resorption: 1alpha,25-(OH)2D3 parathyroid hormone (PTH), IL-1alpha, IL-6 or
      TNF-alpha. CAK was the most abundantly detected CCP and was not increased by
      these stimulants. In the absence of the stimulants, only antisense
      oligodeoxynucleotide (AS-ODN) for CAK suppressed collagenolysis and CCP activity.
      On the other hand, in the presence of the stimulants, AS-ODN for both CAK and CAL
      suppressed collagenolysis and CCP activity, and these activities were additive.
      AS-ODN for CAB did not suppress collagenolysis. These results suggested CAK was
      constitutively synthesized as the main CCP, and CAL was synthesized as an
      inducible CCP in osteoclasts to degrade type-I collagen in combination with CAK.

PMID- 10921448
TI  - Cadmium modulates diabetes-induced alterations in murine neuromuscular junction.
AB  - Skeletal muscle function is compromised in diabetes mellitus and exposure to
      heavy metals may further complicate neuromuscular impairments. The present study
      investigated the effects of cadmium on diabetes induced dorsiflexor muscle
      dysfunction in C57 BL adult male mice. Forty mice were divided randomly into 2
      groups (n=20 each). One group served as control and the other was injected once
      with i.p. streptozotocin (STZ) solution (60 mg/kg) to induce experimental
      diabetes. Each group was then divided into two sub-groups (n=10) of which one
      received 5 mM cadmium. Utilizing intracellular recording method, resting membrane
      potential (RMP) and miniature endplate potentials (MEPPs) were measured in
      dorsiflexor muscle obtained from urethane-anaesthetized (2 mg/g, i.p.) four weeks
      diabetic and matched control mice. Comparative analyses of isometric contractile
      characteristics of in situ dorsiflexor muscle were also conducted in both groups.
      In control mice, flexor muscle exposure to 5 mM cadmium for 10 min resulted in
      significant reduction in MEPPs frequencies and isometric twitch tensions without
      affecting RMP. In STZ-diabetic mice, the same exposure did not modify resting
      membrane potential and further decreased MEPPs frequencies and isometric twitch
      tensions. Current results indicated that cadmium probably via a Ca2+ antagonist
      and chelating activity at nerve terminals exacerbates diabetes complications.

PMID- 10921449
TI  - Interaction between serum leptin levels and hypothalamo-hypophyseal-thyroid axis
      in patients with anorexia nervosa.
AB  - The main objective of the study was to evaluate the endocrinological picture of
      anorexia. Serum leptin levels are low in untreated anorexia nervosa (AN), but
      studies of the exact relationship between leptin, body weight and hormones of
      hypothalamo-hypophyseal-thyroid axis and the impact of refeeding in anorectics
      are limited. The sample consistent of 15 patients with anorexia nervosa before
      and 1 month after partial weight recovery, and 15 age-matched control subjects.
      The body mass index (BMI), leptin, plasma neuropeptide Y (NPY), serotonin,
      thyroxine (T4), triiodothyronine (T3) and reverse triiodothyronine (rT3) in serum
      were evaluated for each subject. The mean serum levels of leptin, T4, and T3 were
      significantly lower before weight recovery in 15 patients with AN than they were
      in control subjects. After partial weight recovery, basal T3 levels were
      unchanged and significantly lower than in controls. Basal T4 was even still more
      reduced, but we observed significantly elevated ratio of T3/T4 and reduced ratio
      rT3/T4 of in AN patients after gain recovery, indicating increased conversion of
      T4 to T3 than to rT3. The levels of serum leptin were low in AN, but after
      partial weight recovery slightly increased, and correlated with BMI. No
      differences were observed in serum NPY. Serum levels of IGF-1 and serotonin were
      lower in AN than in controls before and after partial weight gain. IGF-1 was
      slightly increased after partial weight gain. We did not find correlation between
      serum levels of leptin and serum T4. The low serum levels of T3 associated with
      chronic starvation were thought to be the result of impaired peripheral
      conversion of T4 to T3. However, decreased levels of T3 were still apparent even
      after a partial weight gain, and the concentration of T4 was even lower. The
      diminished serum level of TSH in AN, however, appeared to return to the level of
      controls. On the basis of these results, we assume that low serum levels of
      thyroid hormones in AN reflect a dysfunction of the HPT axis in AN patients. It
      is known that in man serum serotonin levels correlate positively with T3 levels.
      It is possible that the low serum levels of thyroid hormones in AN subjects
      result in low serum serotonin and its product, melatonin. While IGF-1 reflects
      the energy intake of the previous few weeks, the serum leptin concentration
      reflects the true status of the adipose stores, a fact that has useful clinical
      implications.

PMID- 10921451
TI  - Studies on methotrexate effects on testicular steroidogenesis in rats.
AB  - The effects of single dose, 4 consecutive days, 4 and 8 weekly doses of
      methotrexate (MTX) treatment (3 mg/kg body weight, intramuscularly) with and
      without leucovorin (LCN) supplementation (0.3 mg/kg body weight, intramuscularly)
      on serum testosterone titres, total, free and esterified cholesterol
      concentrations and steroidogenic enzymes, viz. 3beta- and 17beta-hydroxy steroid
      dehydrogenase activities were studied in adult albino rats. MTX treatment caused
      a marked reduction in serum testosterone titres in all the treatment groups in a
      duration-dependent manner. LCN supplementation did not restore serum testosterone
      titres to normalcy. Total and free cholesterol concentrations remained unaltered
      in both MTX and MTX + LCN treated groups. On the other hand, a marked increase in
      esterified cholesterol concentration was evident only in weekly dose treatment
      groups. The specific activities of 3beta- and 17beta-hydroxy steroid
      dehydrogenase were markedly diminished in both MTX and MTX + LCN treated groups.
      The results suggest the inhibitory effect of MTX on steroidogenesis.

PMID- 10921450
TI  - Effects of thyroxine on rat brown fat and muscle thermogenesis in the cold.
AB  - We studied whether the activation of rat brown adipose tissue (BAT) by cold
      exposure or by the administration of beta-3-noradrenergic agonist CGP-12177 could
      be prevented by the inhibition of thyroxine (T4) to triiodothyronine (T3)
      conversion. Hypothyroid rats were treated with replacement doses of T4, T4 plus
      iopanoic acid (IA) or T3. Groups of rats were placed at 4 degrees C for 24 h or
      kept at room temperature. Cold exposure induced a significant increase in
      guanosine diphosphate (GDP) binding to BAT mitochondrial proteins in T4-treated
      rats, an effect not abolished by IA. No significant changes were seen in T3
      treated rats. In rats maintained at room temperature and injected with CGP-12177,
      T4 induced a significant rise in GDP binding which was not blocked by IA. T3 also
      induced a significant increase in binding. The study of mitochondrial oxygen
      consumption in muscle from cold-exposed rats showed a marked decrease in
      consumption in T3-treated rats as compared to values in the warm. Normal oxygen
      consumption was restored with 2-fold doses of T3 replacement, whereas 5-fold
      doses increased consumption above normal. The data suggest that in states with
      low or absent T3, T4 can stimulate heat production and preserve normothermia.

PMID- 10921452
TI  - Effect of estrogen-progestin replacement therapy on plasma lipids and
      lipoproteins in postmenopausal women.
AB  - Serum levels of cholesterol (Chol), triglycerides (TG), low-density lipoprotein
      cholesterol (LDL) high-density lipoprotein cholesterol (HDL), both
      apolipoproteins A1 and B (Apo A1, Apo B), follicle-stimulating hormone (FSH)
      luteinizing hormone (LH), estradiol (E2), progesterone (P), testosterone (T) and
      steroid hormone binding globulin (SHBG) were measured in postmenopausal women,
      before and after four different estrogen-progestin replacement therapies. Each
      woman was her own control to avoid genetic or socioeconomic differences. Our
      results showed that serum E2 and TG significantly increased and serum FSH, LH,
      LDH, Apo B, and Chol significantly decreased after all treatments. Serum P and T
      did not significantly change after any of the treatments. HDL, Apo A1 and SHBG
      significantly increased in the groups treated with medroxiprogesterone acetate
      (MPA) but not in the group treated with Norgestrel. We conclude that estrogen
      progestin replacement therapy in postmenopausal women leads to profound and
      beneficial changes in plasma lipids and lipoproteins and that treatments with
      cyclic or continuous MPA could provide greater protection against coronary heart
      disease (CHD).

PMID- 10921453
TI  - Biochemical markers and bone mineral density in patients with hip fractures in
      men.
AB  - The purpose of this study was to determine whether males with hip fractures have
      associated decreased gonadal function. Second void urine and serum samples were
      obtained from 25 male hip fracture patients (mean age+/-SD, 78.5+/-5.9 years) and
      19 age- and gender-matched controls (77.6+/-6.2 years). Serum levels of
      luteinizing hormone (LH), total testosterone (Te), total estradiol (E2),
      dehydroepiandrosterone sulfate (DHEAS), 1,25(OH)2D3, N-mid osteocalcin (OC(N
      mid)), type I collagen degradation products (S-CTx) and urinary levels of
      pyridinoline (Pyr), deoxypyridinoline (Dpyr) and type I collagen degradation
      products (U-CTx) were measured. Bone mineral density (BMD) of the L2-4 spine,
      femoral neck, trochanter, Ward's triangle, distal one third portion of the radius
      and ultradistal radius were also measured in the fracture group. Serum levels of
      LH, E2, Te, DHEAS, 1,25(OH)2D3 and OCN-mid in the fracture group were not
      statistically different from those in the control group. Levels of urinary Pyr,
      CTx and S-CTx in the fracture group increased significantly compared with those
      in the control group. In the fracture group, serum levels of Te correlated
      positively with distal one third portion of the radius BMD and ultradistal radius
      BMD. U-CTx and S-CTx correlated negatively with all the BMD measurement sites in
      the hip region and with the radius BMD. An imbalance between bone resorption and
      bone formation was evident in male hip fracture patients. However, male patients
      with hip fractures did not show associated decreased gonadal function in this
      study.

PMID- 10921454
TI  - Expression of HSD11K (NAD+ dependent 11beta-hydroxysteroid dehydrogenase)
      promoter constructs in renal cell lines.
AB  - The kidney (11-HSD2 or 11-HSDK) isozyme of 11beta-hydroxysteroid dehydrogenase
      confers specificity for aldosterone on mineralocorticoid receptors in target
      tissues. In rodent kidney, this isozyme is expressed mainly in cortical
      collecting ducts and is undetectable in proximal tubules. Using mouse M-1 and
      rabbit RCD cortical collecting duct cells, we analyzed the 5'-flanking region of
      the human HSD11K gene encoding this enzyme in an attempt to identify
      transcriptional regulatory elements responsible for gene expression in the
      kidney. M-1 and RCD cells had high levels of NAD+ dependent 11-HSD activity with
      corticosterone as the substrate. Luciferase reporter constructs containing 1785
      or 327 nucleotides (nt) upstream of the initiator ATG codon were expressed at
      similar levels in each cell line, but deletion to 167 nt almost completely
      abolished expression in both cell types. This region is GC-rich and contain Sp1
      binding sites. Electrophoretic mobility shift assays of the region containing the
      putative Sp1 sites showed several DNA-protein complexes in both the cell types.
      Mutations of the Sp1 sites decreased transcriptional activity in M-1 cells;
      however, these mutations had a marginal effect in the RCD cells. These results
      suggest that elements controlling renal cell type expression are located in the
      proximal 327 nucleotides of the 5' flanking region of HSD11K.

PMID- 10921455
TI  - Serum leptin levels in diabetic patients on hemodialysis: the relationship to
      parameters of diabetes metabolic control.
AB  - Leptin is a protein hormone produced predominantly by adipocytes that affects
      food intake and energy expenditure. Its serum levels are significantly higher in
      patients with chronic renal failure compared to healthy subjects. The aim of this
      study was to compare serum leptin levels in hemodialyzed patients with type II
      diabetes mellitus (n=26) with body content-matched hemodialyzed patients without
      diabetes (n=26) and to explore the relationship between parameters of the long
      term diabetes metabolic control and serum leptin levels. Serum leptin levels in
      diabetic patients did not significantly differ from those of non-diabetic
      patients (25.3+/-8.8 vs 25.7+/-8.7 ng/ml). Serum leptin levels in diabetic
      patients positively correlated with body fat content, body mass index and
      predialysis serum insulin levels. No significant relationship were observed
      between serum leptin levels and blood glucose, glycated hemoglobin, glycated
      protein, serum urea, creatinine, leukocyte count and total hemoglobin
      respectively. The multiple stepwise regression analysis revealed that body fat
      content together with body mass index accounted for 77.8% of variations in
      predialysis serum leptin levels, while insulin levels and the parameters of
      diabetes metabolic control had only slight prediction value for leptin
      concentrations. We conclude that serum leptin levels in hemodialysed patients
      with type III diabetes mellitus do not significantly differ from those of
      hemodialysed non-diabetic patients. The body fat content and body mass index are
      the strongest predictors of serum leptin levels, while parameters of long term
      diabetes metabolic control play probably only minor direct role in its
      regulation.

PMID- 10921456
TI  - The immunology of fetuses and infants.

PMID- 10921457
TI  - What drives the allergic march?

PMID- 10921458
TI  - The role of allergy in childhood asthma.

PMID- 10921459
TI  - Monoclonal antibodies and synthetic peptides define the active site of
      FcepsilonRI and a potential receptor antagonist.
AB  - Defining the structure of the human high-affinity receptor for IgE, Fc,RI, is
      crucial to understand the receptor:ligand interaction, and to develop drugs to
      prevent IgE-dependent allergic diseases. To this end, a series of four anti
      FcepsilonRI monoclonal antibodies (mAbs), including three new mAbs, 47, 54, and
      3B4, were used in conjunction with synthetic FcepsilonRI peptides to define
      functional regions of the Fc IgE-binding site and identify an antagonist of IgE
      binding. The spatial orientation of the epitopes detected by these antibodies and
      their relationship to the IgE-binding region of FcepsilonRI was defined by a
      homology model based on the closely related FcepsilonRIIa. Using recombinant
      soluble FcRI-alpha as well as FcepsilonRI-alpha expressed on the cell surface, a
      series of direct and competitive binding experiments indicated that the mAbs
      detected nonoverlapping epitopes. One antibody (15-1), previously thought to be
      located close to the IgE-binding site, was precisely mapped to a single loop
      within the IgE-binding site by both mutagenesis and overlapping synthetic
      peptides encompassing the entire extracellular domain. A synthetic peptide
      epsilonRI-11, containing the amino acids 101-120 and the mAb 15-1 epitope,
      inhibited IgE binding and may form the basis for the development of a useful
      receptor-based therapy.

PMID- 10921460
TI  - Clinical and immunologic evaluation of Cedrus deodara pollen: a new allergen from
      India.
AB  - BACKGROUND: Allergy to pollen from gymnosperms is well documented in the West.
      However, many allergenic species are native to the Himalayan region of India, and
      Cedrus deodara (Pinaceae) was selected for allergologic investigation. The
      objective was to define the allergologic and immunochemical aspects of C. deodara
      pollen. METHODS: Pollen antigen from C. deodara (CD) was prepared and
      characterized by biochemical and biologic assays. Specific IgE binding was
      determined by means of ELISA and immunoblotting. RESULTS: CD pollen antigen
      caused marked skin sensitivity in 7.5% of an atopic population. A significantly
      elevated level of CD-specific IgE antibodies was observed in 65.8% of the skin
      positive patients. Immunoblotting showed protein fractions of 37, 44, 58, and 78
      kDa with 100% binding with the patients' sera suspected to be due to carbohydrate
      moieties. CONCLUSIONS: Patients from the Himalayan region, where CD occurs
      naturally, were sensitized more than patients from distant places. The
      immunochemical characterization revealed multiple protein fractions from low to
      very high molecular mass (14-126 kDa) mostly in the acidic pI range. CD pollen
      has been recognized as a new allergen from India for the first time. The role of
      pollen as a causative agent of respiratory allergic disorders is very well
      established, as is evident from the recent increase of reports from across the
      world (1-4). India is blessed with the richest flora on the earth, from alpine
      tundra to Rajasthan desert. Consequently, it provides considerable variation in
      the quality and quantity of airborne pollen in different ecogeographic regions of
      the country (5-8). Although studies on the allergenic properties of airborne
      pollen from various species have been carried out by several workers in India (9
      12), information on allergy to aerial pollen from Himalayan tree species has been
      completely

PMID- 10921461
TI  - Usefulness of currently available methods for the diagnosis of Anisakis simplex
      allergy.
AB  - BACKGROUND: Serodiagnosis of anisakiosis and Anisakis allergy is difficult since
      many Anisakis antigens show cross-reactivity complications. In the present study,
      we assess the usefulness of the major immunologic methods currently available for
      the diagnosis of Anisakis allergy. METHODS: Four tests (skin prick test, CAP-FEIA
      system, Western blotting, and an antigen-capture ELISA using O-deglycosylated
      antigen bound by the monoclonal antibody UA3) were applied to Anisakis-free
      subjects and subjects with confirmed Anisakis allergy. RESULTS: The skin prick
      test, CAP-FEIA, and the antigen-capture ELISA identified Anisakis allergy sera
      with 100% sensitivity, while Western blotting showed 96%/ sensitivity. The
      antigen-capture ELISA also showed 100% specificity, but CAP-FEIA showed a
      specificity of only 50%. In Western blotting, none of the bands detected were
      specific for either Anisakis-free or Anisakis allergy subjects. The skin prick
      test was not applied to the Anisakis-free subjects, so its specificity could not
      be determined. CONCLUSIONS: On the basis of these results, we suggest that the
      most appropriate procedure for diagnosis of Anisakis allergy suspected on
      clinical grounds is the antigen-capture ELISA using UA3, or, alternatively, a
      preliminary skin prick test with a positive result subsequently confirmed by UA3
      ELISA.

PMID- 10921462
TI  - Asthma in adults: comparison of adult-onset asthma with childhood-onset asthma
      relapsing in adulthood.
AB  - The prevalence of asthma in children and young adults is rising. Although the
      general features of asthma are similar in children and adults, there are several
      differences. Studies of the differences between childhood- and adult-onset asthma
      may provide new insight into the phenotypic heterogeneity of asthma. The aim of
      this cross-sectional study was to compare the characteristics of asthmatic adults
      who reported having (n = 84) or not having (n = 235) asthma in childhood. The
      participating patients were recruited by chest specialists throughout France and
      were examined from March to November 1995. The specialists completed a
      standardized questionnaire, and carried out a clinical examination and
      spirometric tests. Male sex; greater severity, particularly lower spirometry
      values related to small airways; greater severity and earlier onset of allergy;
      and maternal history of atopic dermatitis and perennial rhinitis were found to be
      associated with reported childhood asthma. This study exhibits highly internally
      consistent results and indicates that subjects who did have childhood asthma and
      relapse in adulthood appeared to have a potentially more severe form of asthma.

PMID- 10921463
TI  - Comparison of serum specific IgE antibodies to staphylococcal enterotoxins
      between atopic children with and without atopic dermatitis.
AB  - BACKGROUND: The skin of patients with atopic dermatitis (AD) exhibits a striking
      susceptibility to colonization and infection by Staphylococcus aureus. The
      exotoxins secreted by S. aureus can act as superantigens and classic allergens,
      inducing the production of functionally relevant specific IgE antibodies. The aim
      of this study was to compare the levels and positive rates of serum
      staphylococcal enterotoxin A (SEA)- and staphylococcal enterotoxin B (SEB)
      specific IgE between atopic children with and without AD. METHODS: Sixty children
      with AD, 55 children with respiratory allergy without AD, and 24 nonatopic
      healthy children were studied. The levels and positive rates of serum SEA- and
      SEB-specific IgE were compared among three groups. The correlation between the
      levels or positive rates of serum SEA/SEB-specific IgE and the severity of AD or
      the presence of previous skin infections was studied. RESULTS: The children with
      AD had significantly higher levels and positive rates of serum SEA- and SEB
      specific IgE than the atopic children without AD (P < 0.001) and the nonatopic
      children (P < 0.001). There was no significant difference in the levels and
      positive rates of serum SEA- and SEB-specific IgE between the atopic children
      without AD and the nonatopic children. With or without adjustment for the
      potential confounding effect of total serum IgE levels, the levels and positive
      rates of serum SEA- and SEB-specific IgE were significantly correlated with
      severity of AD (P <0.005), but they were not significantly different between AD
      children with and without previous skin infections. CONCLUSIONS: SEA and SEB may
      contribute to chronic inflammation and exacerbation of AD through the IgE
      mediated immune response.

PMID- 10921464
TI  - Urinary eosinophil protein X in children: the relationship to asthma and atopy
      and normal values.
AB  - BACKGROUND: In epidemiologic studies, it may be difficult to identify children
      with bronchial asthma. Since this is the most common chronic respiratory disease
      in childhood, and its prevalence is still increasing, reliable methods for
      identification of asthmatic children are required. This study evaluates the use
      of urinary eosinophil protein X (U-EPX) in epidemiologic studies in identifying
      atopic and asthmatic children. METHODS: U-EPX was measured in 877 Austrian
      schoolchildren. The skin prick test (SPT) was performed with eight common
      aeroallergens, and established questionnaires were used to assess respiratory
      symptoms. RESULTS: Of our cohort, 2.8% reported physician-diagnosed asthma, 5.1%
      reported wheezing within the last 12 months, and 24.1% were found to be atopic.
      In children with physician-diagnosed asthma, as well as in atopic children
      (positive SPT), median U-EPX levels were significantly higher than in healthy
      subjects (142.8 and 89.6 vs 63.9 microg/mmol creatinine, P<0.0001 and P<0.0001,
      respectively). In addition, perennial sensitization to inhalant allergens
      resulted in higher U-EPX levels than did seasonal sensitization. The odds ratio
      for U-EPX levels over the 90th percentile was significantly elevated for asthma,
      for wheezing, for nocturnal cough, and for breathlessness at exercise, as well as
      for seasonal and perennial sensitization. Pulmonary function was negatively
      related to U-EPX levels. CONCLUSIONS: Measurement of U-EPX, which can be obtained
      easily, may be helpful in diagnosing both asthma and atopy in children. However,
      there is a great overlap between controls and symptomatics, a fact which reduces
      the sensitivity of U-EPX in determination of the prevalence of asthma in
      epidemiologic studies.

PMID- 10921465
TI  - Reactivity to IgE-dependent histamine-releasing factor is due to monomeric IgE.
AB  - BACKGROUND: IgE-dependent histamine-releasing factor (HRF) can distinguish
      between IgE+ and IgE-. In contrast to IgE-, IgE+ sensitizes basophils to release
      histamine in response to HRF. But we do not know what particular feature
      distinguishes IgE+ from IgE-. The objective was to investigate the hypothesis
      that IgE+ is polymeric IgE. METHODS: IgE+ plasma was separated by size-exclusion
      chromatography. The basophil-sensitizing capacity of the fractions was analyzed
      in response to HRF produced by mononuclear cells. RESULTS: We showed that
      monomeric IgE sensitized basophils to release histamine in response to HRF and to
      house-dust mite, whereas no enhanced reactivity was found in the fractions
      containing polymeric IgE. CONCLUSIONS: HRF reacts with monomeric IgE, and not
      (exclusively) with polymeric IgE.

PMID- 10921466
TI  - Allergenic cross-reactivity of olive pollen.
AB  - BACKGROUND: Sera of patients allergic to olive (Olea europaea) pollen were used
      to analyze the IgE cross-reactivity between olive-pollen extract and other
      pollens obtained from phylogenetically unrelated species. METHODS: We used IgE
      immunostaining of pollen extracts blotted to nitrocellulose membranes after SDS
      PAGE and inhibition analysis of this binding. RESULTS: A high inhibition of the
      IgE binding on olive-pollen extract was exhibited by birch, mugwort, pine, and
      cypress pollens, suggesting that these extracts contain proteins which share
      common epitopes and thus can be recognized by olive-allergic sera. IgE binding to
      Gramineae pollen extracts was not inhibited by olive-pollen extract, indicating a
      primary sensitization of the patients to these species. From the inhibition
      assays, the presence of an allergen of 45 kDa in the olive pollen, which has no
      homologous counterparts in other allergenic species, has been inferred.
      CONCLUSIONS: Olive pollen contains allergens which cross-react with pollens from
      unrelated species, a fact that could simplify the diagnosis and treatment of
      pollinosis.

PMID- 10921467
TI  - Correlation between atopic diseases and tuberculin responses.
AB  - BACKGROUND: In recent decades, the prevalence of atopic diseases has risen
      steadily in developed countries. The reasons for this increase are not clear. It
      has been hypothesized that a reduction in infections and immunization programs
      may contribute to the increase in the prevalence of atopic diseases. We
      investigated the relationship between tuberculin response and atopic disease.
      METHODS: A total of 538 (73.0%) atopic and 198 (27.0%) nonatopic children
      vaccinated with BCG were included in the study. All the children included in the
      study had neither been given BCG nor tuberculin skin-tested in the previous 6
      months, nor did they have a condition known to cause anergy. All the children
      were given five tuberculin units PPD, and PPD indurations were recorded after 48
      h. RESULTS: The PPD induration size was 6.8 +/- 5.6 mm (mean +/- SD) in atopic
      children and 7.4 +/- 5.9 mm in nonatopic children. The difference between the two
      groups was not significant (P > 0.05). The PPD induration sizes of children with
      asthma, rhinitis, and atopic dermatitis were found to be similar. The children
      with atopic dermatitis had lower PPD induration size, but this was not
      statistically significant (P> 0.05). The rates of negative (< 5 mm skin
      induration) and intermediate (5-9 mm) responses were 32.6% and 30.5% in atopic
      children and 30.2% and 32.4% in nonatopic children, respectively. Positive
      tuberculin responses (PPD > 10 mm) were recorded in 36.9% of atopic children and
      37.4% of nonatopic children. Total serum IgE levels of atopic and nonatopic
      children were 623.35 and 46.78 IU/ml, respectively. There was no correlation
      between serum total IgE level and PPD induration size (r = - 0.0012, P = 0.737).
      CONCLUSIONS: We did not find any relationship between tuberculin response and
      atopy status later in life in BCG-immunized subjects. We need further studies to
      clarify the effect of BCG on the development of atopy.

PMID- 10921468
TI  - Loratadine in the treatment of mosquito-bite-sensitive children.
AB  - BACKGROUND: Children frequently experience harmful whealing and delayed papules
      from mosquito bites. Whealing is mediated by antisaliva IgE antibodies and
      histamine, but the effect of antihistamines on mosquito-bite symptoms has not
      been evaluated in children. METHODS: The effect of loratadine (0.3 mg/kg) was
      examined in 28 mosquito-bite-sensitive children (aged 2-11 years). The double
      blind, placebo-controlled, crossover study was performed with exposure to Aedes
      aegypti laboratory mosquitoes. The size of the bite lesion and the intensity of
      pruritus (visual analog scale) were measured at 15 min and at 2, 6, and 24 h.
      RESULTS: Loratadine decreased the size of the wheals by 45% (P < 0.001, 25
      children) and accompanying pruritus by 78% (P = 0.011, 12 children) at 15 min
      compared to placebo. The size of the 24-h delayed bite lesion also decreased
      significantly (P = 0.004), but there was no change at 2 or 6 h. Loratadine was
      well tolerated and no marked side-effects were recorded. CONCLUSIONS: This study
      in children shows that prophylactically given loratadine decreases significantly
      the whealing and pruritus caused by mosquito bites and also reduces the size of
      the 24-h bite lesions. Therefore, the therapeutic profile of loratadine extends
      from immediate to delayed allergic symptoms in mosquito-bite-sensitive children.

PMID- 10921469
TI  - Combining a beta2-agonist with a face mask to prevent exercise-induced
      bronchoconstriction.
AB  - BACKGROUND: In this study, we aimed to test the effect of combining a P2-agonist
      with a heat- and moisture-exchanging cellulose face mask in patients with
      bronchoconstriction induced by exercise in cold air. METHODS: Nine allergic,
      asthmatic patients with a history of adverse reaction to exercise were tested on
      an ergometric bicycle at a temperature of approximately -10 degrees C. They were
      in turn given no treatment, given premedication with a beta2-agonist, allowed to
      breathe through a heat- and moisture-exchanging cellulose face mask, and given
      both premedication and the face mask. After each treatment regimen, they were
      subjected to provocation with exercise and cold air. RESULTS: The decrease in
      FEV, was greatest with no therapy (mean maximal change: 27%), and this diminished
      when the face mask was used (mean maximal change: 12%,) or premedication with a
      32-agonist was given (mean maximal change: 7%); no decrease in FEV1 occurred with
      the combination of agonist and face mask. CONCLUSIONS: The results suggest that
      different mechanisms are involved in the pathophysiology of exercise-induced
      bronchoconstriction (EIB). This finding may be of importance for asthmatic
      athletes who train and compete in a cold climate and are affected by small
      changes in their lung function.

PMID- 10921470
TI  - Anaphylaxis to venom without IgE antibody.

PMID- 10921471
TI  - Sublingual IT in OAS.

PMID- 10921472
TI  - Nitrate intolerance.

PMID- 10921473
TI  - Hypersensitivity to H1-antihistamines.

PMID- 10921474
TI  - Histamine and LTC4 in stinging nettle-induced urticaria.

PMID- 10921475
TI  - Tolerance induction to cotrimoxazole.

PMID- 10921476
TI  - Cross-allergy to ranitidine and nizatidine.

PMID- 10921477
TI  - Reappraisal of single-sample and gamma camera methods for determination of the
      glomerular filtration rate with 99mTc-DTPA.
AB  - The aim of this study was to assess the clinical validity of single-sample
      methods and gamma camera uptake methods with 99mTc-DTPA for the estimation of the
      glomerular filtration rate (GFR). The study was performed in 50 patients with
      various degrees of renal function (29 males and 21 females; age 27-90 yrs; serum
      creatinine level 0.34-6.49 mg/dl). As a reference the "true" GFR (GFRt) was
      determined from plasma clearance by means of the two compartment model curve
      fitting 10 plasma samples. The GFRt of more than 30 ml/min in 46 patients was
      compared to the GFR which was estimated with 7 single-sample methods, two gamma
      camera uptake methods and 24-hour endogenous creatinine clearance (24hCcr). Close
      correlation was observed in all single-sample methods. The highest linear
      correlation was observed in the Christensen and Groth's method rewritten by
      Watson for a 180-min plasma sample (r = 0.991, see = 5.84 ml/min). The smallest
      random error was observed in the Groth and Aasted's method for a 180-min plasma
      (r = 0.989, see = 4.31 ml/min/1.73 m2). Our method was lowest in % absolute
      difference analysis (mean = 4.10%). The gamma camera uptake methods correlated
      significantly with the GFRt (r = 0.746-0.774), but were less reliable than any of
      the single-sample methods (see = 15.41 ml/min-19.14 ml/min). The lowest
      correlation was observed in the 24hCcr (r = 0.698, see = 50.76 ml/min/1.73 m2).
      The single-sample method was more accurate than the gamma camera method, and the
      gamma camera method was more accurate than 24hCcr. The single-sample method
      should be recommended for the accurate determination of the GFR with 99mTc-DTPA
      in a patient with mild to moderate renal dysfunction.

PMID- 10921479
TI  - Hemodynamic and metabolic state of hyperfixation with 99mTc-HMPAO brain SPECT in
      subacute stroke.
AB  - By means of positron emission tomography (PET), we investigated the hemodynamic
      and metabolic state of the hyperfixation identified as the increased accumulation
      with 99mTc-d,l-hexamethylpropyleneamine oxime (HMPAO) by single photon emission
      computed tomography (SPECT) in patients with subacute stroke. We studied four
      patients with subacute stroke having hyperfixed areas evaluated with CBF, CMRO2,
      OEF and CBV by PET. The hyperfixation rate with 99mTc-HMPAO was obtained by
      comparing the surplus rate with standardized CBF. The OEF and CMRO2 values in the
      hyperfixed areas of 4 patients were significantly lower than those in normal 5
      controls (p < 0.01), but CBF and CBV were almost the same in patients and normal
      controls, but the hyperfixation rate of 0.30 +/- 0.15 in 4 patients correlated
      well with CBV (r = 0.97, y = 11.75x + 0.42; p < 0.05). Hyperfixation with 99mTc
      HMPAO in the infarct area revealing a mismatch between CMRO2 and CBF meant
      relative luxury perfusion. The hyperfixation rate determined by 99mTc-HMPAO brain
      SPECT correlated with CBV in the PET study. We can conclude that one of the main
      factors which caused hyperfixation was vasodilatation as well as the blood brain
      barrier disruption and the neovascularization.

PMID- 10921478
TI  - Scintigraphic assessment of regional cardiac sympathetic nervous system in
      patients with single-vessel coronary artery disease.
AB  - In coronary artery disease, the cardiac sympathetic nervous system is closely
      associated with myocardial ischemia. I-123 metaiodobenzylguanidine (MIBG) imaging
      allows us to assess the cardiac sympathetic nervous system regionally. One
      hundred and eleven patients with single-vessel disease underwent regional
      quantitative analysis of MIBG imaging before successful percutaneous transluminal
      coronary angioplasty (PTCA), and repeat angiography 6 months after PTCA. Based on
      the results of the follow-up left ventriculogram, patients were divided into 3
      groups: 39 angina pectoris (AP), 48 prior myocardial infarction without asynergy
      (MI without asynergy) and 24 prior myocardial infarction with asynergy (MI with
      asynergy). AP and MI without asynergy had significant correlations between uptake
      parameters and regional washout in the territory of diseased vessels, among which
      the severity score in AP was the most closely correlated with regional washout (r
      = 0.79, p < 0.0001). These correlations disappeared in MI with asynergy. To
      compare regional MIBG parameters in the territory of the diseased vessel as well
      as in the territories of the other major coronary arteries among the 3 groups, we
      examined MIBG parameters in 57 patients with left anterior descending artery
      (LAD) disease selected from among the study patients. Regional washout in the
      territory of the LAD was significantly higher in the MI without asynergy group
      than in the other two groups. The left circumflex artery (LCX) region showed
      significantly reduced MIBG uptake and an increased extent score in the MI with
      asynergy group compared with the AP group, although only a difference in the
      extent score existed between the MI with asynergy group and the AP group in the
      right coronary artery (RCA) region. In addition, the global ejection fraction
      before PTCA showed a significant negative correlation with each regional washout
      rate. In this way, regional quantitative analysis of MIBG imaging can detect the
      regional differences in the cardiac sympathetic nervous system in coronary artery
      disease, which may be associated with the degree of regional left ventricular
      dysfunction due to myocardial ischemia.

PMID- 10921480
TI  - Impaired coronary microvascular function in diabetics.
AB  - Global and regional myocardial uptake was determined with technetium-99m
      tetrofosmin and a 4 hour exercise (370 MBq i.v.) and rest (740 MBq i.v.)
      protocol, in 24 patients with non-insulin dependent diabetes mellitus and in 22
      control subjects. The purpose of this study was to evaluate impaired coronary
      microvascular function in diabetics by measurement of % uptake increase in
      myocardial counts. The parameter of % uptake increase (deltaMTU) was calculated
      as the ratio of exercise counts to rest myocardial counts with correction of
      myocardial uptake for dose administered and physical decay between the exercise
      study and the rest study. Global deltaMTU was significantly lower in the
      diabetics than in control subjects (14.4 +/- 5.4% vs. 21.7 +/- 8.5%, p < 0.01).
      Regional deltaMTU in each of 4 left ventricular regions (anterior, septal,
      inferior, posterolateral) was significantly lower in the diabetic group than in
      the control group (p < 0.01) respectively, but there were no significant
      differences between deltaMTU in the 4 left ventricular regions in the same group.
      deltaMTU was useful as a non-invasive means of evaluating impaired coronary
      microvascular function in diabetics.

PMID- 10921481
TI  - Rhenium-188-labeled anti-neural cell adhesion molecule antibodies with 2
      iminothiolane modification for targeting small-cell lung cancer.
AB  - We have evaluated the potential of 188Re-labeled monoclonal antibodies (MAbs)
      modified with 2-iminothiolane (2IT) for targeting small-cell lung cancer (SCLC).
      Radiolabeled MAbs NK1NBL1 and C218 recognizing neural cell adhesion molecule were
      injected i.v. into athymic mice inoculated with human SCLC tumors, and the
      biodistribution was examined. NK1NBL1 localized in the tumors better than C218.
      188Re-labeled MAbs cleared from the blood faster than 125I-labeled counterparts,
      resulting in higher tumor-to-blood ratios. In conclusion, the 188Re-labeled MAbs
      are attractive candidates for imaging and therapy of SCLC.

PMID- 10921482
TI  - Exercise myocardial perfusion scintigraphy is useful for evaluating myocardial
      ischemia even in the elderly.
AB  - Pharmacologic stress testing is recommended to elderly patients as a valuable
      alternative to exercise testing. We examined whether exercise testing is as
      useful for evaluating myocardial ischemia in the elderly as in the young. The
      consecutive 1,508 patients who underwent exercise 201Tl single-photon emission
      computed tomography (SPECT) were divided into six age groups: 6-29 years (n =
      56), 30-44 (n = 143), 45-54 (n = 311), 55-64 (n = 498), 65-74 (n = 402), and 75
      88 (n = 98). Both heart rate and rate-pressure product at peak exercise were
      significantly lower in patients aged 75-88 than in the other five groups. The
      frequency of ischemic ST depression was higher in patients aged 75-88 than in
      those aged 6-74, although the difference was not significant. Moreover, the
      frequency of 201Tl transient defect was significantly higher in patients aged 75
      88 than in those aged 6-74. On the other hand, the sensitivity of ischemic ST
      depression for 201Tl transient defect was similar among the six groups, but the
      specificity was significantly lower in patients aged 75-88 than in those aged 6
      74. In conclusion, exercise 201Tl SPECT is useful for evaluating myocardial
      ischemia even in the elderly, but exercise electrocardiography has limitations
      such as lower specificity in the elderly than 201Tl SPECT.

PMID- 10921483
TI  - Resting 123I-BMIPP scintigraphy for detection of organic coronary stenosis and
      therapeutic outcome in patients with chest pain.
AB  - PURPOSE: Resting 123I-BMIPP scintigraphy can detect coronary artery disease based
      on persistent abnormality of myocardial fatty acid metabolism after transient
      ischemia. The present study aimed to determine the value of resting 123I-BMIPP
      scintigraphy in diagnosing coronary artery disease and predicting the therapeutic
      outcome in patients with chest pain symptom. METHOD: Five hospitals participated
      in this study, and scintigraphic and angiographic studies were performed in 104
      patients without myocardial infarction. Twenty of them had non-coronary artery
      disease (chest pain syndrome), 26 had stable effort angina, 35 had unstable
      angina with organic coronary lesions, and 23 had vasospastic angina without
      significant organic stenosis. RESULTS: Overall sensitivity for diagnosing angina
      pectoris (stable, unstable and vasospastic) was 45%, and overall specificity for
      excluding non-coronary artery disease was 80%. The incidence of positive 123I
      BMIPP was 54% among patients with organic coronary stenosis (50% in stable angina
      and 61% in unstable angina with organic stenosis), but it was low (22%) in
      vasospastic angina without organic stenosis. Patients with advanced coronary
      stenosis and multi-vessel disease were found to have a higher incidence of
      positive 123I-BMIPP. A positive 123I-BMIPP result was correlated with a higher
      rate of subsequent intervention therapy (catheter intervention or CABG) than a
      negative result (48% versus 27%, p = 0.03 at one month; and 63% versus 35%, p =
      0.008 at one year). CONCLUSION: Resting 123I-BMIPP scintigraphy was valuable in
      detecting advanced coronary lesions in angina patients associated with a high
      incidence of subsequent intervention therapy.

PMID- 10921484
TI  - Intrasubject correlation between static scan and distribution volume images for
      [11C]flumazenil PET.
AB  - Accumulation of [11C]flumazenil (FMZ) reflects central nervous system
      benzodiazepine receptor (BZR). We searched for the optimal time for a static PET
      scan with FMZ as semi-quantitative imaging of BZR distribution. In 10 normal
      subjects, a dynamic series of decay-corrected PET scans was performed for 60
      minutes, and the arterial blood was sampled during the scan to measure
      radioactivity and labeled metabolites. We generated 13 kinds of "static scan"
      images from the dynamic scan in each subject, and analyzed the pixel correlation
      for these images versus distribution volume (DV) images. We also analyzed the
      time for the [11C]FMZ in plasma and tissue to reach the equilibrium. The intra
      subject pixel correlation demonstrated that the "static scan" images for the
      period centering around 30 minutes post-injection had the strongest linear
      correlation with the DV image. The ratio of radioactivity in the cortex to that
      in the plasma reached a peak at 40 minutes after injection. Considering the
      physical decay and patient burden, we conclude that the decay corrected static
      scan for [11C]FMZ PET as semi-quantitative imaging of BZR distribution is to be
      optimally acquired from 20 to 40 minutes after injection.

PMID- 10921485
TI  - Relationship between striatal [123I]beta-CIT binding and four major clinical
      signs in Parkinson's disease.
AB  - We investigated the correlation between clinical severity and striatal [123I]-CIT
      binding in 12 patients with Parkinson's Disease (PD: 6 men and 6 women, age: 65
      +/- 7 years, Hoehn & Yahr stage: 1 to 3). The clinical severity of PD patients
      was measured with the Unified Parkinson's Disease Rating Scale (UPDRS) after
      withdrawal of antiparkinsonian medication at least 12 hours before assessment.
      [123I]beta-CIT binding in the caudate and putamen was measured at 3 hours [V''3
      (day 1)], and at 24 hours [V''3 (day 2)) after tracer injection with small square
      ROIs. The specific striatal uptake index (day 2) was calculated with large square
      ROIs that encompassed the whole striatum. The best correlation (r = -0.82, p <
      0.0012) was between putamenal V''3 (day 2) and the motor UPDRS scores. When the
      motor UPDRS scores were divided into four subscales, bradykinesia was the only
      sign that correlated significantly with putamenal V''3 (day 2) (r = -0.81, p <
      0.002). [123I]beta-CIT SPECT is a useful marker of disease severity in PD with
      potential utility in the serial monitoring of disease progression.

PMID- 10921486
TI  - Adrenal incidentalomas showing unilateral concordant visualization by
      adrenocortical scintigraphy: comparison with adenomas in Cushing's syndrome.
AB  - An adrenocortical adenoma causing Cushing's syndrome (Cushing's adenoma) produces
      a unilateral concordant visualization (UCV) imaging pattern in which the adenoma
      is only visualized on radioiodocholesterol adrenocortical scintigraphy. But
      because this imaging pattern is also noted in some patients with adrenal
      incidentalomas, we examined whether the UCV-incidentaloma was essentially
      identical with Cushing's adenoma and would develop Cushing's syndrome. The
      subjects were 9 patients with UCV-incidentalomas (mean size, 30 mm; range, 20-45
      mm) and 6 patients with Cushing's adenomas (mean size, 28 mm; range, 25-35 mm).
      Endocrinological evaluations showed several abnormalities including blunted
      diurnal rhythm of plasma cortisol within the normal range, low plasma ACTH and/or
      high 24-hr urinary 17-OHCS levels in 8 of 9 patients with UCV-incidentalomas, but
      these abnormalities did not meet the diagnostic criteria of Cushing's syndrome.
      Adrenal uptake of the tracer in the patients with UCV-incidentalomas was not
      statistically different from that in the patients with Cushing's adenomas and had
      no relationship with hormonal values in either patient group. Tumor size on CT
      correlated with the levels of 24-hr urinary 17-OHCS (r = 0.75, p = 0.02) and
      plasma cortisol at 7:00 (r = 0.82, p = 0.007) in the patients with UCV
      incidentalomas, but not in the patients with Cushing's adenomas. Although 3 UCV
      incidentalomas increased slightly in size, none of 9 patients with UCV
      incidentalomas has developed Cushing's syndrome for 4 to 52 months. These results
      suggest that the UCV-incidentaloma may be essentially different from the
      Cushing's adenoma and unlikely to develop Cushing's syndrome.

PMID- 10921487
TI  - Evaluation of persistence of ductus venosus with tc-99m DTPA galactosyl human
      serum albumin liver scintigraphy and I-123 iodoamphetamine per-rectal portal
      scintigraphy.
AB  - Tc-99m DTPA galactosyl human serum albumin (Tc-99m GSA) hepatic scintigraphy was
      performed in two patients with patent ductus venosus before and after operation.
      To evaluate the portosystemic shunt flow, per-rectal portal scintigraphy with I
      123 N-isopropyl-p-iodoamphetamine (IMP) was undergone in the same period. The
      portosystemic shunt indices (PSS index) were decreased from 67.9% to 7.3% in the
      patient 1, and from 77.3% to 22.7% in the patient 2, respectively. Quantitative
      indices of Tc-99m GSA hepatic scintigraphy improved dramatically in both
      patients. Under microscopic examination, nearly all the hepatic cells showed
      signs of severe fatty degeneration. After the operation, the severe fatty
      degeneration was alleviated and all the hepatic cells appeared normal. I-123 IMP
      per-rectal portal scintigraphy and Tc-99m GSA hepatic scintigraphy were useful in
      evaluating the quantitative shunt flow of the persistent ductus venosus and its
      hepatic functional reserve.

PMID- 10921488
TI  - Transient right-to-left shunt in massive pulmonary embolism.
AB  - A 56-yr-old man, two months after an operation for an acoustic neurinoma,
      gradually developed dyspnea. Massive pulmonary embolism (MPE), with a significant
      right-to-left (R-L) shunt, was seen in a perfusion scan of the lungs with Tc-99m
      MAA. Radioactivity was noted in the thyroid, spleen, kidneys and brain. A cardiac
      ultrasound study did not reveal intracardiac shunting. A few days later, when the
      patient's condition improved, another perfusion scan of the lungs did not show
      the shunt, whereas a subsequent digital subtraction angiographic study confirmed
      the diagnosis of MPE but failed to reveal the cause of the shunt. In the absence
      of any possible pathophysiological mechanism, to explain the observed R-L shunt,
      we deduce that the particles of Tc-99m MAA might have passed through the
      precapillary pulmonary arteriovenous anastomoses and/or through dilated pulmonary
      capillaries, as a result of highly increased pulmonary vascular pressure due to
      MPE.

PMID- 10921489
TI  - Hypoperfusion of right hemisphere on brain SPECT in a patient with exanthem
      subitum and left hemiparesis.
AB  - Left hemiparesis exhibited during the post-eruptive stage of exanthem subitum
      (ES) in an 11-month-old girl. Tc-99m HMPAO brain SPECT showed diffuse
      hypoperfusion in right hemisphere. Hemiparesis has occasionally been reported as
      central nervous system (CNS) complications of ES, and Tc-99m HMPAO brain SPECT
      was useful for evaluating of CNS involvement.

PMID- 10921490
TI  - Gallium-67 scintigraphic findings in a patient with breast lymphoma complicated
      with Sjogren syndrome.
AB  - We report here a patient with mucosa associated lymphoid tissue (MALT)-lymphoma
      of the breast complicated with Sjogren syndrome. It is speculated that Ga-67
      could accumulate not only in lymphoma lesions but also in benign
      lymphoproliferative locations of Sjogren syndrome. Gallium-67 scintigraphy might
      be useful for the diagnosis and therapeutic monitoring of MALT-lymphoma
      complicated with Sjogren syndrome.

PMID- 10921491
TI  - Course before and after percutaneous transhepatic portal vein embolization of a
      patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl
      human serum albumin.
AB  - Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the
      embolized lobe and compensatory hypertrophy of the nonembolized lobe, and
      improves the safety of hepatectomy. We report a patient with cholangiocarcinoma
      who underwent embolization of both anterior and posterior branches of the right
      portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum
      albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe
      of the liver was atrophied and the left lobe of the liver was enlarged, compared
      with before PTPE. The receptor index of the entire liver was almost unchanged
      before and after PTPE, but the right lobe receptor index after PTPE was 23% less
      than the pre-PTPE value, whereas the left lobe receptor index had increased 37%.
      Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating
      segmental functional reserve before and after PTPE.

PMID- 10921492
TI  - Serial changes in N-isopropyl-p[125I]-iodoamphetamine in mouse lung observed with
      a confocal laser scanning microscope.
AB  - Serial changes in N-isopropyl-p[125I]-iodoamphetamine (125I-IMP) in mouse lungs
      were observed with a confocal laser scanning microscope. Male mice were
      intravenously injected with 125I-IMP and subjected to autoradiographic procedures
      20 minutes, and 3 and 24 hours after injection. Differential interference
      contrast (DIC) images and confocal images were obtained with a confocal laser
      scanning microscope, and superimposed images were evaluated. Large numbers of
      silver grains were observed in the interstitium, bronchioles, and alveolar sacs
      20 minutes after the injection, and lamellar distribution of the grains was
      observed on the ciliary surface. The numbers of silver grains in the interstitium
      and bronchioles had decreased 3 hours after the injection of 125I-IMP, but the
      numbers of silver grains in the alveolar spaces had not. Although small numbers
      of silver grains remained in both the bronchioles and alveolar sacs 24 hours
      after the injection, most of them had washed out. Confocal laser scanning
      microscopy is considered to be a useful procedure for studying the distribution
      of radioisotopes by microautoradiography, because it allows clear autoradiographs
      to be obtained in which tissues and silver grains are perfectly matched and all
      silver grains are in focus.

PMID- 10921493
TI  - Measles--United States, 1999.
AB  - State and local health departments reported a provisional total of 100 confirmed
      measles cases to CDC in 1999. This total equals the record low number of cases
      reported in 1998 (1). Since 1997, measles incidence in the United States has
      remained < or = 0.5 cases per 1,000,000 population. This report describes the
      epidemiology of measles during 1999, which indicates that measles is not endemic
      in the United States.

PMID- 10921494
TI  - Compliance with physical activity recommendations by walking for exercise-
      Michigan, 1996 and 1998.
AB  - Physical inactivity is an important modifiable risk factor for many diseases,
      including cardiovascular disease, cancer, diabetes, and osteoporosis. The 1996
      Surgeon General's report (1) recommended that persons of all ages obtain "a
      minimum of 30 minutes of physical activity of moderate intensity (e.g., brisk
      walking) on most, if not all, days of the week." Walking is encouraged as one of
      the most accessible ways to be physically active (2), is the most commonly
      reported leisure-time physical activity (LTPA) in the United States, and is
      relatively common among groups that are typically inactive (e.g., the elderly and
      low-income groups) (3). To determine whether exercise characteristics (i.e.,
      duration, frequency, and speed of walking) of Michigan adults met the Surgeon
      General's recommendations, the Michigan Department of Community Health analyzed
      data from the 1996 and 1998 Michigan Behavioral Risk Factor Surveillance System
      (BRFSS) for those who reported walking as their only LTPA. This report summarizes
      the results of this analysis, which indicate that most walkers need to increase
      the frequency and perhaps the speed of their walking to comply with
      recommendations.

PMID- 10921495
TI  - Outbreak of gastroenteritis associated with an interactive water fountain at a
      beachside park--Florida, 1999.
AB  - Since 1989, approximately 170 outbreaks associated with recreational water venues
      (e.g., swimming pools, waterparks, fountains, hot tubs and spas, lakes, rivers,
      and oceans) have been reported, with almost half resulting in gastrointestinal
      illness (1-5). This report summarizes the investigation of an outbreak of
      gastroenteritis in Florida during 1999. The findings indicated that Shigella
      sonnei and Cryptosporidium parvum infections caused illness in persons exposed to
      an "interactive" water fountain at a beachside park.

PMID- 10921497
TI  - National, state, and urban area vaccination coverage levels among children aged
      19-35 months--United States, 1999.
AB  - Childhood vaccinations have a major impact on the reduction and elimination of
      many causes of morbidity and mortality among children (1). Monitoring vaccination
      coverage levels is necessary to characterize undervaccinated populations and to
      evaluate the effectiveness of efforts to increase coverage. The National
      Immunization Survey (NIS) provides ongoing national estimates of vaccination
      coverage among children aged 19-35 months based on data for the most recent 12
      months for each of the 50 states and 28 geographic areas (2). This report
      presents the findings of the 1999 NIS, which indicate that vaccination coverage
      among U.S. children aged 19-35 months were at or near record high levels.

PMID- 10921496
TI  - Progress toward poliomyelitis eradication--South-East Asia Region, 1998-1999.
AB  - In 1988, the World Health Assembly resolved to eradicate poliomyelitis by the end
      of 2000 (1). To achieve this goal, the 10 member countries of the World Health
      Organization (WHO) South-East Asia Region (SEAR) began implementing polio
      eradication strategies in 1994. In 1999, most polio cases worldwide were reported
      in SEAR (i.e., 48% of reported polio cases and 62% of cases with wild poliovirus
      isolation) (2,3). This report summarizes progress in achieving high routine and
      supplemental vaccination coverage, the surveillance of cases of acute flaccid
      paralysis (AFP), and the impact of these activities on polio eradication in the
      region during 1998-1999.

PMID- 10921498
TI  - Prevalence of intimate partner violence and injuries--Washington, 1998.
AB  - Approximately 20% of emergency department visits for trauma and 25% of homicides
      of women involve intimate partner violence (IPV) (1,2). To assess IPV prevalence
      in Washington, the Washington State Department of Health added questions from the
      Conflict Tactics Scale (3) and the Revised Conflict Tactics Scale (4) to its 1998
      Behavioral Risk Factor Surveillance System (BRFSS) survey. This report describes
      an analysis of responses to the questions, which indicated that women were more
      likely than men to experience IPV in their lifetime, and more than three times
      more likely than men to experience injuries from IPV.

PMID- 10921499
TI  - Update: Nucleic acid amplification tests for tuberculosis.
AB  - On September 30, 1999, the Food and Drug Administration approved a reformulated
      Amplified Mycobacterium Tuberculosis Direct Test (MTD) (Gen-Probe, San Diego,
      California) for detection of Mycobacterium tuberculosis in acid-fast bacilli
      (AFB) smear-positive and smear-negative respiratory specimens from patients
      suspected of having tuberculosis (TB). MTD and one other nucleic acid
      amplification (NAA) test, the Amplicor Mycobacterium Tuberculosis Test (Amplicor)
      (Roche Diagnostic Systems, Inc., Branchburg, New Jersey), previously had been
      approved for the direct detection of M. tuberculosis in respiratory specimens
      that have positive AFB smears. This notice updates the original summary published
      in 1996 (1) and provides suggestions for using and interpreting NAA test results
      for managing patients suspected of having TB. The appropriate number of specimens
      to test with NAA will vary depending on the clinical situation, the prevalence of
      TB, the prevalence of nontuberculous mycobacteria (NTM), and laboratory
      proficiency (2,3). Based on available information, the following algorithm is a
      reasonable approach to NAA testing of respiratory specimens from patients with
      signs or symptoms of active pulmonary TB for whom a presumed diagnosis has not
      been established.

PMID- 10921500
TI  - Early bone growth in chickens genetically selected for a high and low growth
      rate.
AB  - Male chickens from lines divergently selected for fast (FGL) and slow (SGL)
      growth were compared for the growth of cortical bone. Morphology,
      histomorphometric, compositional and biomechanical properties of the tibiotarsi
      were analysed in both lines at 1, 8, 15 and 22 d of age. Tibial morphology
      (length, volume, cross-section and diameters) was similar in FGL and SGL chickens
      when compared at an equal body weight. Cortical area was also similar in both
      lines at an equal body weight but cortex porosity was higher in FGL. Tibial
      mineral density (ash:volume) was higher in FGL than in SGL at hatching and at 8 d
      of age. Biomechanical properties were lower in SGL than in FGL at 8 d of age, but
      then became higher in this line when compared at equal body weight. The very slow
      growth rate in SGL did not modify bone size when chickens were compared at equal
      body weight. Bone quality was modified in various ways: in SGL bone structure was
      strengthened by a lower porosity of the cortex while bone tissue was less
      mineralized up to 22 d of age. In both lines, cortical growth was slower than in
      commercial cross-breeds and bone quality (structure and composition) was improved
      compared to broilers.

PMID- 10921501
TI  - Dietary protein effects on the broiler's adaptation to triiodothyronine.
AB  - The purpose of this experiment was to study the effects of dietary protein on
      metabolic adaptations in birds given triiodothyronine (T3) at 28 d of age.
      Knowledge about the role of dietary protein in thyroid metabolism is lacking.
      Male broiler chickens were fed diets containing either 120 or 300 g crude
      protein/kg from 7 to 28 d. At this time, one-half of each group was given that
      diet supplemented with 1 mg/kg T3. Birds were sampled at 0, 2, 5, 7, 9 and 12 d
      following the initiation of the T3 treatments. Measurements taken at these
      intervals included in vitro lipogenesis (IVL), growth and feed consumption,
      hepatic enzyme activities and plasma thyroid hormones and metabolites. As
      expected, IVL was greater at 28 d in birds fed the lower level of protein.
      Moreover, when T3 was added to either diet, IVL decreased by 50% after 5 d.
      Plasma IGF-I and T4 were greater while T3 and GH were less when birds were fed
      the higher level of crude protein. Plasma T3 increased and T4 decreased 3 d
      following the addition of T3 to diets containing either level of crude protein.
      Most metabolic changes in response to feeding T3 occurred within 2 to 5 d,
      suggesting that changes in intermediary metabolism preceded morphological changes
      that we have previously seen. In addition, dietary protein levels may not affect
      adaptive responses to T3.

PMID- 10921502
TI  - Correlations between skeletal muscle mass and bone mass in children 6-18 years:
      influences of sex, ethnicity, and pubertal status.
AB  - A constant sex-specific relationship between skeletal muscle mass and bone mass
      was observed in healthy adults based on TBK/TBCa, using TBK (total body
      potassium) by 40K counting and TBCa (total body calcium) by in-vivo neutron
      activation analysis (Ellis and Cohn, 1975). We revisited this topic in children
      by studying correlations between TBK and TBCa, and by comparing TBK/TBCa between
      sexes, pubertal groups (prepubertal and pubertal) and ethnic groups in 141 white,
      101 black, and 62 Asian healthy children, aged 6 - 18 years, living in New York
      City. TBK was measured by 40K counting, and TBCa by dual energy x-ray
      absorptiometry. TBK and TBCa were significantly correlated from 6 to 18 years (r
      > 0.93), but the correlation equations varied by gender and ethnicity. Boys had
      significantly more TBK and greater TBK/TBCa than girls at a given age and weight,
      reflecting greater skeletal muscle mass in boys from 6 years, the age at which
      the study started. TBK/TBCa in blacks was significantly smaller than whites and
      Asians in both sexes in prepuberty and puberty, and pubertal black girls had the
      smallest mean TBK/TBCa. No significant differences were found between whites and
      Asians. TBK/TBCa decreased as body weight increased in prepubertal girls, and
      decreased as body weight and age increased in pubertal girls, but did not change
      with body weight or age in boys of any subgroup. The inverse relationship between
      TBK/TBCa and age in pubertal girls suggests greater increase in TBCa compared to
      TBK than in other groups, while the constant TBK/TBCa in boys reflects
      proportional increases in TBK and TBCa. Thus TBK/TBCa can be used as an index of
      relative growth in skeletal muscle mass and bone mass in white, black, and Asian
      children according to sex, age and pubertal status.

PMID- 10921503
TI  - Growth of functional cranial components in Saimiri sciureus boliviensis
      (Cebidae): a longitudinal study.
AB  - Ten male Saimiri sciureus boliviensis (Cebidae) born at the Centro Argentino de
      Primates (CAPRIM) were divided into a control group (five animals fed ad libitum
      on a 20% protein diet) and an undernourished group (five animals fed ad libitum
      on a 5% protein diet) at weaning (seven months old). Each animal was radiographed
      monthly from both later-lateral and dorsal-ventral views, from the first to the
      third year of age. The length, width and height of the optic, respiratory, and
      masticatory components of the face and anterior neural, middle neural, and
      posterior neural components were measured in the radiographs. Volumetric (VI) and
      morphometric (MI) indices were calculated for each component. Correlations and
      simple linear regressions with respect to age were performed. In the face, two
      components -respiratory and masticatory- showed the greatest growth rate. In the
      neurocranium, the middle neural component grew most, approaching the rate
      observed for the component of the lowest growth in the face (optic). The anterior
      neural and posterior neural components showed the lowest -although significant-
      growth rates of the skull. The determination coefficients showed that linearity
      explained from 12% (posterior neural component) to 74% (masticatory component) of
      the variation, the remainder being attributed to shape changes and noise effects.
      The neurofacial rate showed a high level (80%) of nonlinearity since the
      neurocranium grew almost 1/3 with respect to the face. The morphometric indices
      showed that only the masticatory component was linear to the face. While the
      respiratory component grew more, the optic one grew less than the whole face.
      Only the anterior neural component kept linearity with the neurocranium. While
      the middle neural component grew more, the posterior neural one grew less than
      the whole neurocranium. Significant alterations due to undernutrition were seen
      in both major components. While the three facial and the anterior neural
      components showed correlation coefficients lower -but significant- than in
      controls, in the remaining indices -morphometrics included- the correlation
      values were abruptly broken. The slopes of the regressions which remained
      significant showed that undernutrition affected mainly the components with
      greater growth rates (respiratory, masticatory, and middle neural). Secondarily
      affected were those with lower growth rates (optic, anterior neural and posterior
      neural), despite their function and according to the histology of the organs they
      support and protect.

PMID- 10921505
TI  - The local effect of PAF on leukocyte adherence to small bowel mesenteric venules
      following intra-abdominal contamination.
AB  - We have previously demonstrated that intra-abdominal contamination increases
      neutrophil infiltration into the gastrointestinal tract. The purpose of our
      current study was twofold: 1) to determine if leukocyte adherence to the
      mesenteric microvasculature occurred by local peritoneal contamination or by
      systemic mechanisms; and 2) to assess the role of platelet activation factor
      (PAF) in this process. Rats underwent cecal ligation and puncture (CLP), and 4 h
      after the procedure we used intravital microscopy to visualize the mesenteric
      microcirculation. Cecal ligation and puncture increased leukocyte adherence
      (22.3+/-5.5 leukocytes/100 microm) vs. sham (2.3+/-0.9, P < 0.05). WEB-2086, a
      PAF receptor antagonist, prevented this increase (6.47+/-4.8, P < 0.05). To
      assess if leukocyte adherence was due to topical effects, we performed similar
      experiments with the small bowel exteriorized. In such cases, CLP did not
      increase leukocyte adherence (1.2+/-0.8 vs. 1.4+/-0.9). In addition, topical
      application of highly diluted fecal matter (1:1000) increased leukocyte adherence
      (4.8+/-1.2) vs. control (0.6+/-0.3, P < 0.05). Our study demonstrates that
      leukocyte adherence in the mesenteric microcirculation following intra-abdominal
      contamination is due to direct topical exposure to fecal matter, and it is
      mediated by PAF.

PMID- 10921504
TI  - Selective involvement of reactive oxygen intermediates in platelet-activating
      factor-mediated activation of NF-kappaB.
AB  - Although it has been suggested that some biological activities of platelet
      activating factor (PAF) are mediated by, at least in part, reactive oxygen
      intermediates (ROI), the precise mechanisms underlying the interaction between
      the two remains to be elucidated. Antioxidants, such as alpha-tocopherol acid
      succinate, N-acetyl-L-Cysteine, pyrrolidinedithiocarbamate failed to inhibit PAF
      induced immediate systemic reactions such as lethality, symptoms of disseminated
      intravascular coagulation, and histological changes such as pulmonary edema and
      hemorrhage in renal medullae 10 min following PAF injection. In contrast.
      antioxidants significantly inhibited both the in vivo and in vitro PAF-induced NF
      kappaB activation and NF-kappaB-dependent TNF-alpha expression. The effects of
      the antioxidants were due to their inhibition of PAF-induced degradation of
      IkappaBalpha, a protein responsible for keeping NF-kappaB in an inactive form. A
      protein tyrosine kinase and N-tosyl-L-phenylalanine chloromethyl ketone sensitive
      serine protease were involved in both PAF- and H2O2-induced NF-kappaB activation.
      Collectively, these data indicate that the PAF-induced NF-kappaB activation is
      selectively mediated through the generation of ROI.

PMID- 10921506
TI  - Effects of tranexamic acid and aprotinin, two antifibrinolytic drugs, on PAF
      induced plasma extravasation in unanesthetized rats.
AB  - Two antifibrinolytic drugs, tranexamic acid (TXA), and aprotinin (APR), are
      currently used to improve the recovery of patients following major surgery while
      reducing blood loss. Their mechanisms of action have yet to be fully understood.
      Here, we examined (1) the effects of TXA or APR on basal vascular permeability
      (VP) and (2) the effects of TXA or APR on platelet-activating factor (PAF)
      induced increase of VP in normal unanesthetized rats. Evans blue dye (EB) bound
      to albumin was used as the marker of extravasation in selected tissues. In normal
      rats, PAF (1 microg/kg i.v.) increased VP in most selected tissues including
      bronchi, aorta, duodenum and pancreas without affecting blood pressure. TXA (up
      to 300 mg/kg i.v.) had no significant effect on basal VP in any tissues, while
      APR (30000 KIU/kg i.v.) decreased basal VP in 5 out of 8 tissues. Pre-treatment
      with TXA decreased PAF-induced increases of VP in the microcirculation of the
      thoracic and abdominal aorta, the duodenum and the pancreas, from 35% to 41%. TXA
      was mostly effective at an i.v. dose of 100 mg/kg with a 2 h of pre-treatment
      period. Pre-treatment with APR also reduced PAF-induced increases of VP in
      selected tissues by 35 to 61%. The i.v. dose of 30000 KIU/mg was optimal when
      injected at least 30 min before the administration of PAF + Evans blue. These
      results suggest that the beneficial effect of APR and TXA, following
      cardiopulmonary bypass (CPB) and other type of surgeries, may be attributed to
      the inhibition of plasma exudation mediated, at least in part, by PAF. Thus, TXA
      and APR may improve patients recovery by reducing the capillary leakage of
      albumin, associated with interstitial edema formation, and maintaining
      intravascular fluid volume.

PMID- 10921507
TI  - Nitric oxide inhibits INFgamma-induced increases in CIITA mRNA abundance and
      activation of CIITA dependent genes--class II MHC, Ii and H-2M. Class II
      TransActivator.
AB  - BACKGROUND: Nitric oxide (NO) has been recently implicated as a powerful
      inhibitor of immune responses during allograft rejection, and some autoimmune and
      infectious diseases. We previously showed that one potential regulatory effect of
      NO is inhibition of IFNgamma-stimulated expression of Class II MHC on
      macrophages. Activation of this gene is mediated by the "Class II TransActivator"
      (CIITA). We now ask whether NO inhibits CIITA and thus the family of genes
      regulated by CIITA--Class II MHC, Ii, and H-2M. The latter two genes participate
      in antigen processing and formation of the cell-surface peptide-Class II MHC
      complex. METHODS: Murine macrophages--both peritoneal macrophages and the
      RAW264.7 macrophage line--were stimulated in vitro with IFNgamma. NO production
      was measured by the Greiss reagent. Transcription of Class II MHC was measured by
      nuclear run-on assay. mRNA abundance of Class II MHC, Ii, H-2M, and CIITA was
      measured by Northern blotting and RT-PCR. RESULTS: NO inhibits IFNgamma-induced
      increases in the abundance and transcription of the Class II MHC Ab gene. The
      increases in mRNA abundance of CIITA, Ii, and H-2M are also inhibited. As a
      control, we found that NO did not inhibit LPS-induce increases in TNFalpha mRNA
      abundance. CONCLUSIONS: NO inhibits IFNgamma-induced increases in CIITA, and thus
      inhibits the CIITA-regulated genes: Class II MHC, Ii, and H-2M. Early during
      rejection, NO production by macrophages may result after stimulation by IFNgamma
      produced by CD4+ T cells, and be an effector of allograft damage. High
      concentrations of NO may then act as a feedback inhibitor which decreases antigen
      presentation by macrophages and thus decreases CD4 T cell activation.

PMID- 10921508
TI  - Cytokine mRNA in the joints and draining lymph nodes of rats with adjuvant
      arthritis and effects of cyclosporin A.
AB  - TNF-alpha and IL-1beta promote leukocyte recruitment to arthritic joints and may
      contribute to cartilage degradation while regulatory cytokines such as IL-4 and
      IL-1RA may in part determine the course of arthritis. Here we report the pattern
      of TNF-alpha, IL-1beta, IL-6, IFN-gamma, IL-1RA, and IL-4 mRNA expression,
      detected by RT/PCR, in the talar joint and draining popliteal lymph node (PLN) of
      rats with adjuvant arthritis (AA). Levels of TNF-alpha and IFN-gamma mRNA were
      increased in the PLN before clinical signs of arthritis. This was followed by
      increases in IL-1beta and IL-1RA mRNA at d9 and IL-6 mRNA at d12. PLN IL-1RA mRNA
      levels were positively correlated with those of IL-1beta and TNF-alpha throughout
      d5-d20. IL-4 mRNA levels were highest on days 7 and 20. In the synovium, a small
      increase in TNF-alpha, IL-1beta, and IL-6 mRNA was detected on d5 then again on
      d12. Maximal synovial TNF-alpha levels were reached on d20, while IL-1beta peak
      expression was on d16 and IL-6 on d14. IL-4, IL-1RA, and IFN-gamma mRNA was
      undetectable in the synovium. Cyclosporin treatment for 4 days, initiated at the
      height of arthritis, rapidly decreased clinical disease, and decreased migration
      of neutrophils and T lymphocytes into the joints. Yet no significant effect of
      CyA was observed on inflammatory cytokine expression, although the correlation
      between PLN IL-1RA and IL-1beta or TNF-alpha was lost in treated animals. Thus
      there is a variable pattern of cytokine gene expression in rat AA, the
      undetectable IL-4 and IFN-gamma mRNA in synovium being analogous to human
      rheumatoid arthritis.

PMID- 10921509
TI  - Morphine stimulates mesangial cell TNF-alpha and nitrite production.
AB  - BACKGROUND: Intravenous opiate abusers are susceptible to develop heroin and HIV
      associated nephropathies; however, the role of opiates in the development of
      these kidney lesions is not clear. Patients with opiate addiction are prone to
      recurrent infections. METHODS: The effect of morphine was studied on the
      generation of TNF-alpha with or without LPS (lipopolysaccharide) by cultured
      mouse mesangial cells. In addition, the effect of morphine was evaluated on
      mesangial cell nitrite production. To evaluate the role of opiate receptors, we
      studied the effect of naloxone and naltrexone on mesangial cell TNF-alpha and
      nitrite production. To determine the role of TNF-alpha on mesangial cell nitrite
      production, we examined the effect of anti-TNF-alpha antibody on morphine-induced
      nitrite production. Assay of TNF-alpha and nitrite production was carried by
      ELISA and Griess method respectively. RESULTS: Morphine alone did not enhance the
      generation of TNF-alpha by mesangial cells, however, an enhanced (P < 0.001) TNF
      alpha production was observed when mesangial cells were first treated with
      morphine for 18 h and then activated further with LPS. Maximum release of TNF
      alpha was seen at a concentration of 10(-12) M of morphine. Opiate receptor
      antagonists (naloxone and naltrexone) inhibited the effect of morphine. Morphine
      also amplified (P < 0.0002) the effect of LPS on mesangial cell nitrite
      production. Anti-TNF-alpha antibody attenuated morphine induced nitrite
      generation. CONCLUSION: We conclude that morphine stimulates the generation of
      TNF-infinity by LPS-activated mesangial cells. This effect of morphine seems to
      be opiate receptor mediated and has a downstream effect in the form of mesangial
      cell nitrite generation. The present in vitro study provides the basis for a
      hypothesis that morphine may be playing a role in the development of heroin and
      HIV-associated nephropathies.

PMID- 10921511
TI  - Short-term benefit from oral vancomycin treatment of regressive-onset autism.
AB  - In most cases symptoms of autism begin in early infancy. However, a subset of
      children appears to develop normally until a clear deterioration is observed.
      Many parents of children with "regressive"-onset autism have noted antecedent
      antibiotic exposure followed by chronic diarrhea. We speculated that, in a
      subgroup of children, disruption of indigenous gut flora might promote
      colonization by one or more neurotoxin-producing bacteria, contributing, at least
      in part, to their autistic symptomatology. To help test this hypothesis, 11
      children with regressive-onset autism were recruited for an intervention trial
      using a minimally absorbed oral antibiotic. Entry criteria included antecedent
      broad-spectrum antimicrobial exposure followed by chronic persistent diarrhea,
      deterioration of previously acquired skills, and then autistic features. Short
      term improvement was noted using multiple pre- and post-therapy evaluations.
      These included coded, paired videotapes scored by a clinical psychologist blinded
      to treatment status; these noted improvement in 8 of 10 children studied.
      Unfortunately, these gains had largely waned at follow-up. Although the protocol
      used is not suggested as useful therapy, these results indicate that a possible
      gut flora-brain connection warrants further investigation, as it might lead to
      greater pathophysiologic insight and meaningful prevention or treatment in a
      subset of children with autism.

PMID- 10921510
TI  - Anti-inflammatory effect of pirfenidone in the bleomycin-hamster model of lung
      inflammation.
AB  - We have previously reported the antifibrotic effects of pirfenidone (PD) in the
      bleomycin (BL)-hamster model of lung fibrosis. Since the development of fibrosis
      is generally preceded by acute lung inflammation, the present study was conducted
      to find out if dietary intake of PD (0.5%) has any effects on BL-induced lung
      inflammation. In this regard, we evaluated the effects of PD on BL-induced
      increased pulmonary vascular permeability, increased influx of inflammatory cells
      and increased levels of TGF-beta in the bronchoalveolar lavage fluid (BALF).
      Hamsters were intratracheally (IT) instilled with saline (SA) or BL (5.5
      units/kg/5 ml). The animals were fed the control diet (CD) or the same diet
      containing 0.5% PD 2 days prior to IT instillation and throughout the study. The
      bronchoalveolar lavage was carried out at different times after IT instillation.
      Lavage fluid was used for total and differential cell counts and BALF-supernatant
      for measurement of total protein and TGF-beta. IT instillation of BL caused
      significant increases in total cells, neutrophils, macrophages and lymphocytes
      and in the levels of total protein and TGF-beta in BALF from hamsters in the BL +
      CD groups as compared to the corresponding SA + CD control groups. In contrast,
      treatment with pirfenidone in general, suppressed the BL-induced increases in the
      levels of proteins and TGF-beta and in the influx of neutrophils, macrophages and
      lymphocytes in BALF at the early time points in BL + PD groups. Based on the data
      reported in this study, we conclude that the anti-inflammatory effects of
      pirfenidone as evident by suppressions of BL-induced increased pulmonary vascular
      permeability and increased influx of inflammatory cells in the lung contribute
      additionally to its inherent anti-fibrotic effect.

PMID- 10921513
TI  - Growth patterns among infants with language deficits: a case-control study.
AB  - We compared growth parameters in infants with language delay to those in children
      with global delay and to typical controls. Thirty infants with expressive
      language delay and 36 with combined expressive and receptive language delay were
      compared with 27 infants with general development delay and with 124 controls.
      Data on weight, height, head circumference, and feeding behavior were obtained
      from birth up to age 78 weeks, and converted to percentiles. Medical and
      sociodemographic data were also evaluated. The weight curves in the combined
      expressive and receptive language delay group were significantly lower than in
      the comparison groups, but no cases of failure to thrive were noted. Height and
      head circumference curves in the combined expressive and receptive language delay
      group were also lower than in the typical controls. Infants with combined
      expressive and receptive language delay were lighter and shorter than controls.
      However, none of the parameters were more than two standard deviations below the
      mean. It is possible that this finding is of constitutional origin.

PMID- 10921512
TI  - Bone mineral density and turnover in children with attention-deficit
      hyperactivity disorder receiving methylphenidate.
AB  - Attention-deficit hyperactivity disorder (ADHD) is the most common behavior
      disorder among children; methylphenidate is a drug frequently prescribed for the
      control of its symptoms. One of the potential side effects of methylphenidate
      that concerns parents is its impact on the growth of children, since the
      mechanism by which methylphenidate might influence growth is not known. As linear
      growth is associated with an increase in bone mineral density and turnover, this
      study was undertaken to evaluate bone mineral density by dual photon
      absorptiometry and bone turnover by measuring serum bone-specific alkaline
      phosphatase and the urinary deoxypyridinoline excretion rate in children treated
      with methylphenidate for 1 to 2 years as compared to a control group. There were
      no significant differences in bone mineral density at either the lumbar spine or
      femoral neck in the study group (0.662 +/- 0.04 and 0.735 +/- 0.07 g/cm2,
      respectively) as compared to the controls (0.675 +/- 0.05 g/cm2 and 0.734 +/-
      0.07 g/cm2, respectively). Furthermore, there were no significant differences in
      serum bone-specific alkaline phosphatase in the study group (58 +/- 22 U/L) as
      compared to the control children (71 +/- 34 U/L) or in urinary deoxypyridinoline
      in the study group (34 +/- 38 nM/mM), as compared to the control group (27 +/- 12
      nM/mM). In conclusion, our data do not support a significant effect of
      methylphenidate on bone mineral density turnover in children when used for 1 to 2
      years.

PMID- 10921514
TI  - Mitochondrial respiratory-chain defects presenting as nonspecific features in
      children.
AB  - Patients with mitochondrial respiratory-chain defects frequently exhibit lactic
      acidosis, ragged red fibers in skeletal muscle samples, and abnormal enzyme
      assays for the respiratory-chain complex. However, ragged red fibers and lactic
      acidosis are not always seen in all patients with mitochondrial respiratory-chain
      defects. We have encountered six children with biochemically proven respiratory
      chain defects, but typical ragged red fibers were not found in all six patients,
      and only five patients had increased serum lactate levels. Initially, they
      present with nonspecific features. However, persistent or progressive clinical
      features or multiple organ involvement eventually led to the diagnosis of
      respiratory-chain defects in these patients. Mitochondrial respiratory-chain
      defects should be considered in the differential diagnosis when persistent,
      progressive features and especially multiple organ involvement occur.

PMID- 10921516
TI  - Idiopathic intracranial hypertension in children.
AB  - We studied prospectively the etiology, clinical presentation, and outcome of
      idiopathic intracranial hypertension in 36 patients (20 boys and 16 girls) aged
      3.5 months to 14 years. The etiology was identified in 28 (77.7%) patients. The
      most common predisposing factor was middle-ear infection, followed by obesity. Of
      the 36 cases seen, 26 presented with the classic picture of headaches,
      papilledema, and elevated cerebrospinal fluid pressure; 8 children had
      intracranial hypertension in the absence of papilledema and 2 had fundoscopic
      evidence of papilledema with normal cerebrospinal fluid pressure initially. In
      four children resolution of intracranial hypertension occurred with removal of
      the causative agent or appropriate treatment of the underlying condition. In 8 of
      17 patients intracranial hypertension resolved with acetazolamide therapy and in
      22 of 24 patients it resolved with corticosteroids in combination with
      acetazolamide. Subnormal visual acuity, narrowing of visual fields, or both were
      present on the initial examination in 10 patients; 2 of them, who presented with
      loss of vision, have permanent visual impairment. Four additional patients
      presented a transient, mild impairment of visual acuity during treatment. Our
      study confirms the wide clinical spectrum and the difficulties encountered in
      diagnosis of idiopathic intracranial hypertension. A wide variety of etiologic
      associations should be investigated to provide definitive therapy. Loss of visual
      function is the only serious complication.

PMID- 10921515
TI  - Rapid eye movement sleep in breath holders.
AB  - One-night polysomnography was performed on seven subjects suffering from breath
      holding spells, including one whose death was suggested to be a consequence of a
      breath-holding spell. The fatal case showed no rapid eye movements (REMs) during
      REM sleep, although he exhibited REMs during wakefulness. The average numbers of
      both REMs and bursts of REMs in REM sleep in the other six breath holders were
      significantly lower than those in age-matched controls. The breath holders showed
      no airway obstruction, desaturation, or sleep fragmentation. Since the rapid
      ocular activity in REM sleep is generated in the brain stem, we hypothesized that
      a functional brainstem disturbance is involved in the occurrence of breath
      holding spells.

PMID- 10921517
TI  - Congenital Minamata disease: warnings from Japan's experience.
AB  - Minamata disease is alkylmercury poisoning causing Hunter-Russell syndrome due to
      ingestion of seafood polluted by industrial waste. Two epidemics occurred in
      Minamata (1956) and Niigata (1965), Japan. Many infants with "cerebral palsy" in
      villages where adult cases occurred were established as having congenital
      Minamata disease. Developing brains were affected by alkylmercury through
      transplacental exposure and even by breastfeeding. This report reviews the
      history, clinical features, pathology, epidemiology, metal analysis, experiments,
      and sociolegal aspects of congenital Minamata disease. Many victims are still
      alive and their present conditions are reviewed.

PMID- 10921518
TI  - Positron emission tomography in imaging spinal cord tumors.
AB  - The ability of positron emission tomography (PET) to detect spinal cord tumors
      was studied prospectively in 14 patients presenting over a 5-year period.
      Abnormal uptake by [18F]-fluorodeoxyglucose (FDG) or 11C-methionine was detected
      in all except one. These data were assessed in relation to magnetic resonance
      imaging (MRI) findings with regard to tumor type and extent preoperatively,
      findings at operation, and subsequent clinical course. The group consisted of six
      astrocytomas, five ependymomas, one mixed ependymoma and astrocytoma, one
      schwannoma, and one ganglioglioma, all confirmed histologically. This is the
      largest study comparing spinal PET to MRI. Accurate preoperative correlation
      between PET and MRI was found in all eight patients scanned at first
      presentation. The PET uptake was in keeping with the low-grade histology of the
      tumors. Postoperatively, PET and MRI findings were in agreement in nine patients.
      In eight of these the findings were in keeping with the subsequent clinical
      course. In three patients, however, the PET findings were at variance with the
      clinical course and MRI findings. In one, persistent FDG uptake after
      radiotherapy was seen where there was subsequent tumor resolution. In two
      patients with low-grade astrocytomas, scanned with FDG and 11C-methionine,
      respectively, tracer was not taken up by residual tumor. In this small group of
      patients, PET did not provide additional useful information. This could be
      because all tumors studied were low grade and the limited spatial resolution of
      PET does not lend itself to imaging small spinal cord tumors. The prospective
      study of larger numbers of patients with a wider range of tumor types is
      required, but this might be difficult to achieve given the rarity of spinal cord
      tumors.

PMID- 10921519
TI  - Evidence that Alpers-Huttenlocher syndrome could be a mitochondrial disease.
AB  - We report an 11-year-old boy with a slight developmental delay and epilepsy.
      After he was placed on valproate, he developed hepatic failure and increasing
      neurologic symptoms, including epilepsia partialis continua, and died. Autopsy
      findings in liver and cerebrum were consistent with progressive neuronal
      degeneration of childhood with liver disease, also called Alpers-Huttenlocher
      syndrome. Ragged red fibers and cytochrome c oxidase negative fibers were present
      in muscle. These results suggest that Alpers-Huttenlocher syndrome, at least in
      some patients, is a mitochondrial disease.

PMID- 10921520
TI  - Weinberg's syndrome: a disorder of attention and behavior problems needing
      further research.
AB  - A subset of inattentive children have an underlying problem in sustaining
      wakefulness ("vigilance"). This disorder of vigilance, termed Weinberg's
      syndrome, is characterized by difficulty in maintaining wakefulness and alertness
      as evidenced by (among other symptoms) motor restlessness (fidgeting and moving
      about, yawning and stretching, talkativeness) and complaints of tiredness. During
      tasks requiring concentration (continuous mental activity) such as reading,
      children with Weinberg's syndrome will daydream, lose interest, complain of
      boredom, and become increasingly restless. Napping, while infrequent, usually is
      not refreshing. A distinct personality described by family members and friends as
      kind, affectionate, compassionate, or "angelic" also seems to characterize this
      condition. Weinberg's syndrome has a familial pattern suggesting autosomal
      dominant inheritance. Additional neurophysiologic, pharmacotherapeutic,
      epidemiologic, and genetic studies will be necessary for a full understanding of
      Weinberg's syndrome.

PMID- 10921521
TI  - Subacute central nervous system degeneration in a child: an unusual manifestation
      of ifosfamide intoxication.
AB  - A 5-year-old child with desmoplastic small round-cell tumor was treated with a
      protocol of very-high-dose, short-term chemotherapy, containing HD-CAV
      (cyclophosphamide, doxorubicin, vincristine, and mesna), ifosfamide, and
      etoposide. Two days after the initiation of ifosfamide, he exhibited new-onset
      lethal encephalopathy manifested by subacutely progressive cerebellar and then
      temporal and frontocortical degeneration leading to a vegetative state and
      eventually to death. A full work-up, including brain biopsy, was negative,
      excluding infections and metabolic or vascular causes. Ifosfamide is known to be
      capable of causing acute encephalopathy that can be severe but is generally
      reversible. This child showed a very atypical progressive, lethal course of
      ifosfamide toxicity. The possibility of this complication should be considered
      when high-dose ifosfamide treatment is planned for children.

PMID- 10921522
TI  - Spontaneous recovery from severe encephalitis involving cerebellar gray matter.
AB  - We report a case of cerebellitis displaying a severe neurologic onset but with
      spontaneous recovery, challenging the use of immunomodulatory treatment.

PMID- 10921523
TI  - Temporary pure red-cell aplasia during valproate monotherapy: clinical
      observations and spectral electroencephalographic aspects.
AB  - We report the case of a 4-year-old boy with pure red-cell aplasia associated with
      sodium valproate monotherapy. Treatment with valproate was initiated because of
      idiopathic tonic-clonic seizures; he became free of seizures. During the
      introduction of and ongoing antiepileptic drug treatment, clinical and laboratory
      controls using electroencephalographic (EEG) spectral analysis were performed at
      regular intervals and disclosed normal values. Ten months after the introduction
      of valproate, clinical examination was normal except for marked pallor.
      Peripheral blood showed macrocytic anemia and the bone marrow finding was
      isolated absolute erythroblastopenia. At the same time, significant changes in
      EEG background activity were present as well-defined slowing. There was an
      increase in the relative power of theta activity and a decrease in alpha 2
      activity in the occipital regions. Valproate was discontinued and phenobarbital
      therapy introduced. A complete resolution of the hematologic damage was observed
      after valproate withdrawal. Recovery of the hematologic parameters started 14
      days after discontinuation of valproate therapy, while normalization of EEG
      background activity was observed earlier. The patient maintained stable
      hematologic values and seizure control without disturbances of the spectral EEG.
      After 6 months of phenobarbital therapy, re-administration of sodium valproate
      was not followed by recurrence of any clinical or electrophysiologic symptoms or
      abnormalities.

PMID- 10921526
TI  - Identification and characterization of I1 imidazoline receptors: their role in
      blood pressure regulation.
AB  - It has been shown that only imidazolines and related compounds cause a fall in
      blood pressure when administered at the site of the hypotensive action of
      clonidine; no phenylethylamine compounds were capable of producing such an effect
      at this site. Extensive biochemical and pharmacologic studies have confirmed the
      involvement of imidazoline receptors in the regulation of vasomotor tone and in
      the mechanism of action of some centrally acting antihypertensive drugs.
      Imidazoline-specific binding sites (IBS) did not bind catecholamines. Functional
      studies using selective antagonists have confirmed that the hypotensive effects
      of clonidine-like drugs are mediated by imidazoline-specific receptors, whereas
      their sedative action clearly involves alpha2-adrenergic receptors located in the
      locus coeruleus. Compared with clonidine, second-generation centrally acting
      antihypertensive drugs such as rilmenidine have been shown to be more selective
      for imidazoline receptors than for alpha2-adrenergic receptors. This selectivity
      may explain the reduced incidence of side effects of these drugs at hypotensive
      doses. Very recently, new imidazoline-like compounds have been synthesized that
      are highly selective for both subtypes of IBS (I1 and I2). Some of these
      compounds lowered blood pressure when injected centrally in animals, indicating
      that an action on imidazoline I1 receptors alone is sufficient to lower blood
      pressure. With the help of such selective tools, we have also shown that
      imidazoline receptors and alpha2-adrenoceptors might cooperate to control
      vasomotor tone, and might jointly be involved in the hypotensive action of
      centrally acting hybrid drugs (ie, drugs that bind to both types of receptor).

PMID- 10921525
TI  - Diffuse polymicrogyria associated with congenital hydrocephalus,
      craniosynostosis, severe mental retardation, and minor facial and genital
      anomalies.
AB  - We report an infant boy with an apparently new malformation syndrome. The major
      anomalies showed by the patient include diffuse polymicrogyria, congenital
      hydrocephalus, craniosynostosis with severe scaphocephaly, severe mental
      retardation, intractable epilepsy, and minor facial and genital anomalies. Our
      review of the literature and two computerized dysmorphology databases found some
      papers reporting polymicrogyria or lissencephaly associated with craniosynostosis
      or hydrocephalus. None of the reported patients had a phenotype similar to that
      of our patient.

PMID- 10921524
TI  - D-2-hydroxyglutaric aciduria with cerebral, vascular, and muscular abnormalities
      in a 14-year-old boy.
AB  - D-2-Hydroxyglutaric Aciduria is a rare metabolic disorder that can cause injury
      to the brain and other organs. This case report concerns a 14-year-old boy
      showing irritability and typical signs of pyloric stenosis early postnatally.
      From the age of 3 months he had epilepsy. He was mentally retarded, hypotonic
      with preserved reflexes, and dystonic. The features were dysmorphic with
      elongated head and high arched palate. Cardiomegaly with aortic insufficiency was
      diagnosed. Magnetic resonance imaging of the brain revealed atrophy, reduced
      periventricular white matter, and multiple bilateral aneurysms of the middle
      cerebral arteries. The boy died at the age of 14 years. Autopsy confirmed the
      white-matter reduction of the cerebral hemispheres as well as the arterial
      aneurysms of the middle cerebral arteries. Lesions of a few leptomeningeal and
      cerebral microvessels and of the renal and pulmonary arteries were also found.
      There were bilateral infarcts of the kidneys and signs of cardiomyopathy with
      noncompensated left ventricular failure. Signs of myopathy were evident. The
      clinical and postmortem findings imply a disseminated mesenchymal process.

PMID- 10921527
TI  - I1 imidazoline receptors in cardiovascular regulation: the place of rilmenidine.
AB  - From the very earliest suggestion of a distinction between imidazoline receptors
      and alpha2-adrenoceptors, there has been much debate as to their contribution to
      the antihypertensive actions of clonidine-like agents. However, with the
      development of drugs such as rilmenidine that are more selective for I1
      imidazoline receptors, their role and also their close relationship with alpha2
      adrenoceptors has become clearer. We have examined this question using a range of
      imidazoline and alpha2-adrenoceptor antagonists given centrally and peripherally
      to conscious rabbits. We found that second-generation agents such as rilmenidine
      preferentially act via imidazoline receptors but that alpha2-adrenoceptors are
      important for the hypotension produced by the first-generation agents clonidine
      and alpha-methyldopa. In addition to the hypotension, rilmenidine facilitates
      cardiac vagal baroreflexes and inhibits cardiac sympathetic baroreflexes and
      diminishes the increase in renal sympathetic activity produced by environmental
      stress. In other studies using anesthetized rabbits and direct measures of
      sympathetic nerve activity, we confirmed that the major site of
      sympathoinhibitory actions and sympathetic baroreflex effects of rilmenidine is
      the rostral ventrolateral medulla. Our results also suggest that alpha2
      adrenoceptors are activated as a consequence of imidazoline receptor activation
      by rilmenidine. Thus, though imidazoline receptors appear to be the primary
      target of rilmenidine, "downstream" alpha2-adrenoceptors within the brainstem are
      also involved and need to be considered in developing pharmacologic strategies
      for antihypertensive treatment involving imidazoline agents.

PMID- 10921528
TI  - The sympathetic system and hypertension.
AB  - Measurement of regional sympathetic activity in lean essential hypertension
      patients using electrophysiologic (sympathetic nerve recording) and neurochemical
      (measurement of norepinephrine spillover) techniques demonstrates activation of
      sympathetic outflow to the heart, kidneys, and skeletal muscle vasculature in
      younger (< 45 years) patients. The increase in sympathetic activity is a
      mechanism for both initiating and sustaining the blood pressure elevation.
      Sympathetic nervous activation also confers specific cardiovascular risk.
      Stimulation of the sympathetic nerves to the heart promotes the development of
      left ventricular hypertrophy and contributes to the genesis of ventricular
      arrhythmias and sudden death. Sympathetically mediated vasoconstriction in
      skeletal muscle vascular beds reduces the uptake of glucose by muscle, and is
      thus a basis for insulin resistance and consequent hyperinsulinemia.
      Understanding the neural pathophysiology of obesity-related hypertension has been
      more difficult. In normotensive obesity, renal sympathetic tone is doubled, but
      cardiac norepinephrine spillover (a measure of sympathetic activity in the heart)
      is only 50% of normal. In obesity-related hypertension, there is a comparable
      elevation of renal norepinephrine spillover, but without suppression of cardiac
      sympathetics, as here cardiac norepinephrine spillover is more than double that
      of normotensive obese and 25% higher than in healthy volunteers. Increased renal
      sympathetic activity in obesity may be a necessary cause for the development of
      hypertension (predisposing to hypertension development), but apparently is not a
      sufficient cause. The discriminating feature of the obese who develop
      hypertension is the absence of the presumably adaptive suppression of cardiac
      sympathetic outflow seen in the normotensive obese. The sympathetic nervous
      system has moved towards center stage in cardiovascular medicine. The importance
      of sympathetic activation in heart failure progression and mortality and in the
      generation of ventricular arrhythmias is now well established. In essential
      hypertension also, although the mechanism differs somewhat between the lean and
      obese, the sympathetic nervous system is a key factor in the genesis of the
      disorder, and additionally promotes the development of complications. Through
      their central inhibition of sympathetic nervous activity, I1 agents such as
      rilmenidine powerfully reduce sympathetic nervous activity in essential
      hypertension patients, lowering blood pressure, and carrying the potential for
      specific cardiovascular protection.

PMID- 10921529
TI  - Rilmenidine: a clinical overview.
AB  - Rilmenidine is an antihypertensive agent with selectivity for I1 imidazoline
      receptors that acts both centrally by reducing sympathetic overactivity and in
      the kidney by inhibiting the Na+/H+ antiport. Rilmenidine provides
      antihypertensive efficacy comparable with that of diuretics, beta-blockers,
      calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors.
      Experience from trials and clinical practice highlights rilmenidine's clinical
      and metabolic acceptability in hypertensive populations, including those at
      special risk because of old age, renal impairment, diabetes mellitus, or
      dyslipidemia. In the at-risk hypertensive, rilmenidine reduces left ventricular
      hypertrophy to a similar degree to other reference agents. New studies show a
      significant improvement in glucose metabolism in metabolic syndrome patients
      treated with rilmenidine, and a significant reduction in microalbuminuria during
      rilmenidine treatment of hypertensive type 2 diabetics. Thus the
      efficacy/tolerance ratio of rilmenidine supports its role as a first-line
      antihypertensive option for all groups of hypertensive patient, with specific
      advantages in some at-risk populations.

PMID- 10921530
TI  - Autonomic imbalance, hypertension, and cardiovascular risk.
AB  - Essential hypertension conveys an increased risk of cardiovascular morbidity and
      mortality. The common finding of an autonomic imbalance in these patients
      contributes not only to the etiology of hypertension itself, but also to the
      cardiac risk and resulting adverse sequelae. A high sympathetic tone in
      particular is responsible for many of the metabolic, hemodynamic, trophic, and
      rheologic abnormalities that cluster in patients with high blood pressure.
      Methods to clarify the respective importance of prereceptor versus receptor
      abnormalities for the etiology of insulin resistance are warranted. Results of
      large hypertension clinical trials examining the degree of cardioprotection
      offered by newer medications that are neutral or beneficial to the vast array of
      underlying abnormalities are a few years away. In the meantime, utilization of
      antihypertensive drugs that reduce sympathetic overactivity and are metabolically
      beneficial is a reasonable clinical alternative in hypertensive patients with the
      metabolic syndrome or with signs of autonomic imbalance.

PMID- 10921531
TI  - Efficacy of rilmenidine, a selective I1 imidazoline receptor binding agent in
      diabetic hypertensive patients.
AB  - Hypertension is a frequent complication in diabetes, and microalbuminuria has
      become an essential index of cardiovascular prognosis in type 2 diabetics. The
      pilot study reported here shows that rilmenidine, in addition to its
      antihypertensive action and good clinical tolerability, has the further advantage
      of reducing microalbuminuria, similar to captopril.

PMID- 10921532
TI  - Use of bioelectrical impedance techniques for monitoring nutritional status in
      patients on maintenance dialysis.
AB  - Malnutrition continues to be an important correlate of survival in dialysis
      patients. Nutritional surveillance at the clinical level requires use of simple,
      reasonably accurate, and easily accessible techniques for multicompartmental body
      composition analysis. Unfortunately, although gold standard methodologies (body
      density by underwater weight, total body water by isotope dilution, bone mineral
      content by neutron activation, total body potassium by (40)K whole body gamma
      counting) provide very precise assessments, they are not applicable to routine
      clinical practice. Because of its availability and simplicity, bioelectrical
      impedance (BEI) has significant potential as a complement to standard
      anthropometric techniques in the nutritional monitoring of patients with chronic
      renal failure. Consistency of technique and standardization of BEI equipment are
      essential for reproducibility of results. Several studies have validated the use
      of total body water by BEI as a surrogate for isotope dilution methods in
      dialysis patients, whereas others have established an excellent correlation with
      the volume of distribution of urea as measured by urea kinetic volume.
      Bioimpedance analysis for measurement of lean body mass has been extensively
      evaluated in stable healthy populations, with results similar to those obtained
      using hydrodensitometry and total body potassium. In dialysis patients, accuracy
      is contingent on a stable hydration status and/or appropriate correction for
      changes in extracellular volume status over time. Recent publication of
      bioimpedance norms for the hemodialysis population allows better comparisons with
      the national reference population studied as part of the National Health and
      Nutrition Examination Survey III (US Department of Health and Human Services,
      Centers for Disease Control and Prevention, National Center for Health
      Statistics, Hyattsville, MD). BEI methodology is a practical bedside tool for
      assessment of body composition that provides more consistent and reproducible
      results than standard anthropometry alone.

PMID- 10921533
TI  - Sevelamer with and without calcium and vitamin D: observations from a long-term
      open-label clinical trial.
AB  - OBJECTIVE: To determine the effects of sevelamer hydrochloride on serum
      phosphorus, calcium, calcium x phosphate product, and parathyroid hormone (PTH)
      in patients treated with and without vitamin D metabolites and calcium
      supplementation. DESIGN: Long-term, open-label clinical trial. SETTING:
      Hemodialysis units. PATIENTS: One hundred ninety-two adult patients with end
      stage renal disease on hemodialysis. INTERVENTION: An extended treatment period
      of sevelamer hydrochloride, preceded and followed by phosphate binder washout
      periods. MAIN OUTCOME MEASURES: Treatment-related changes in serum phosphorus,
      calcium, calcium x phosphate product, and PTH. RESULTS: Subjects treated with
      sevelamer alone, sevelamer with vitamin D metabolites (with or without calcium),
      and sevelamer with calcium without vitamin D experienced significant reductions
      in mean serum phosphorus (range, 2.1 to -2.9 mg/dL) and the calcium x phosphate
      product (range, -16.3 to -23.4 mg2/dL2). The mean serum calcium concentration
      increased in all subgroups except those treated with sevelamer alone (range, +0.3
      to +0.5 mg/dL). In contrast, only subjects treated concurrently with vitamin D
      metabolites experienced a reduction in PTH. Subjects treated with sevelamer alone
      or sevelamer with calcium without vitamin D experienced an increase in PTH with
      treatment. CONCLUSION: Sevelamer hydrochloride is a safe and effective phosphate
      binder in hemodialysis patients. Sevelamer should be used in combination with
      vitamin D metabolites to jointly control hyperphosphatemia and
      hyperparathyroidism. Randomized clinical trials will be required to determine the
      optimal management strategies for metabolic bone disease in end-stage renal
      disease, as well as less advanced stages of chronic renal insufficiency.

PMID- 10921534
TI  - Changes in plasma free and phospholipid-bound choline concentrations in chronic
      hemodialysis patients.
AB  - BACKGROUND: Choline deficiency may develop in malnourished patients, those with
      cirrhosis, and those who require total parenteral nutrition. Previous data has
      suggested an important role for the kidneys in the maintenance of choline
      homeostasis. OBJECTIVE: This study was undertaken to determine the change in
      plasma choline during hemodialysis and to determine if it was lost in the
      dialysate. DESIGN: Thirteen adult patients (10 men, 3 women) who had required
      hemodialysis for a mean of 10.8 years were studied. Dialysis was performed 3
      times weekly for 4 hours using either a cellulose acetate or polysulfone dialyzer
      membrane. Venous and arterial blood, and dialysate samples were taken for
      measurement of plasma free and phospholipid-bound choline concentration before
      beginning dialysis and after each hour of dialysis. An in vitro system was
      devised to determine if choline could bind to a significant degree to the
      dialysis membrane. RESULTS: Plasma free choline concentration was increased above
      normal (11.7 +/- 3.7 nmol/mL) at baseline and declined progressively during
      dialysis. In contrast, plasma phospholipid-bound choline concentration increased
      progressively during dialysis. The decrease in plasma free choline (-1.8 +/- 0.3
      nmol/mL(-1)/h(-1); P = 1.6 x 10(-6)) was almost entirely related to that which
      was removed during dialysis, although the magnitude of the loss was not
      correlated with the increase in plasma phospholipid-bound choline concentration
      (125 +/- 20.5 nmol/mL(-1)/h(-1); P < 1.2 x 10(-6)). Patients lost a mean of 246
      pmol of free choline during hemodialysis. Choline did not bind to the dialysis
      membrane. CONCLUSION: Plasma free choline concentration is elevated before
      dialysis, and choline is lost to a significant degree in the dialysate. Further
      investigation is necessary to determine whether a transient, dialysis-induced
      choline deficiency develops, and whether there is a role for choline
      supplementation in these patients. The choline homeostatic mechanism requires
      further investigation in renal failure patients.

PMID- 10921535
TI  - Nutritional status and its relationship to quality of life in a sample of chronic
      hemodialysis patients.
AB  - OBJECTIVE: To assess the relationship between nutritional status and quality of
      life in a sample of chronic hemodialysis patients. DESIGN: Cross-sectional study.
      SETTING: Haemodialysis Units of St Vincent's and St George Hospitals, Sydney,
      Australia. PATIENTS: Sixty-four patients participated in the nutritional
      assessment, of which 53 completed the quality of life questionnaire.
      INTERVENTION: Nutritional status was assessed using subjective global assessment
      in addition to a number of anthropometric and biochemical parameters. Quality of
      life was assessed by means of a patient questionnaire and assessment of physical
      functioning. MAIN OUTCOME MEASURES: Nutrition status, 6 quality of life subscales
      related to general well-being, health and functioning, social and economic,
      psychological/spiritual well-being, and family life, employment status, income,
      participation in recreational/sports activities, the number of hospital
      admissions, days of hospitalization, and lengths of hospital stay. RESULTS: Sixty
      four percent of patients were well nourished, 23% were moderately malnourished,
      and 13% were severely malnourished. Malnutrition was associated with poorer
      subjective quality after controlling for the affects of sociodemographic and
      medical variables. Severe malnutrition was also independently associated with
      poorer physical function, and resulted in significantly more hospital admissions,
      more days of hospitalization, and longer average lengths of hospital stay.
      CONCLUSION: Malnutrition is common in chronic hemodialysis patients and is
      associated with poorer quality of life when the degree of malnutrition becomes
      severe. Prospective studies are required to determine whether improving the
      nutritional status of these patients will result in meaningful improvements in
      quality of life and other medical outcomes.

PMID- 10921536
TI  - The effects of zinc supplementation on serum zinc concentration and protein
      catabolic rate in hemodialysis patients.
AB  - OBJECTIVE: To examine the effect of zinc sulfate supplementation on serum zinc
      concentrations and protein catabolic rate (PCR) in hemodialysis (HD) patients.
      DESIGN: Randomized, double-blind, before-after trial. SETTING: Outpatient
      dialysis center in a large metropolitan city. PATIENTS: Twenty-eight maintenance
      HD patients were selected. Twenty (15 women, 5 men) subjects completed the study.
      Subjects were identified for inclusion in the study by the following criteria: a
      history of low PCR (<0.09 g/kg body weight), HD treatment for a minimum of 6
      months, no signs of gastrointestinal disorders, and no record of hospitalizations
      for reasons other than access complication within the last 3 months.
      INTERVENTIONS: Patients consumed 7.7 pmol zinc sulfate (2,200 microg) or a
      cornstarch placebo capsule daily for 90 days. In addition, patients completed a 2
      day food record representative of 1 dialysis day and 1 nondialysis day. MAIN
      OUTCOME MEASURE: Fasting, predialysis serum samples were collected on days 0, 40,
      and 90 to determine serum zinc concentration and PCR. Dietary parameters
      including intake of zinc, protein, and energy were analyzed on Days 0 and 90.
      RESULTS: Initial analysis at Day 0 of serum zinc concentration indicated subjects
      were below the normal range for serum zinc standards (12.2 micromol/L [80
      microg/dL]). After supplementation, subjects in the zinc-supplemented group
      showed significant increases in serum zinc concentrations from 12.2 micromol/L
      (80 microg/dL) at Day 0 to 15.3 pmol/L (100 microg/dL) at Day 90. A significant
      positive correlation (r = +0.61) was shown between PCR and serum zinc
      concentrations at the end of the study. Reported dietary protein intake did not
      change with zinc supplementation. CONCLUSION: Low serum zinc concentrations are
      reversible with zinc supplementation. Improvement in serum zinc concentration
      increases the PCR of HD patients.

PMID- 10921537
TI  - Estrogen replacement therapy: a possible mode of combating the effects of renal
      osteodystrophy?
AB  - Because of the complications of renal osteodystropy, female patients with end
      stage renal disease have difficulty maintaining bone health. Smaller, less dense
      bones puts this patient population at risk for increased bone loss and fractures.
      For years, estrogen replacement therapy has been used as an effective form of
      treatment in women suffering from bone loss related to osteoporosis. More recent
      research has focused on the effects of estrogen therapy in combination with other
      supplements such as calcium, magnesium, vitamin D, calcitonin, and soy.
      Unfortunately, the role of estrogen replacement therapy in the female end-stage
      renal disease patients has not been fully explored. Research in these areas may
      provide valuable information to practitioners looking for another means to combat
      renal bone disease.

PMID- 10921538
TI  - Nutrition guidelines after kidney transplantation.

PMID- 10921539
TI  - Diabetic patients have a decreased incidence of acute respiratory distress
      syndrome.
AB  - OBJECTIVE: Our ability to predict which critically ill patients will develop
      acute respiratory distress syndrome (ARDS) is imprecise. Based on the effects of
      diabetes mellitus on the inflammatory cascade, we hypothesized that a history of
      diabetes might alter the incidence of ARDS. DESIGN: A prospective multicenter
      study. SETTING: Intensive care units at four university medical centers.
      PATIENTS: One hundred thirteen consecutive patients with septic shock.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients were
      prospectively followed during their intensive care course for the development of
      ARDS. A history of diabetes was identified in 28% (32/113) of the patients. In
      this study, nondiabetics were more likely to develop septic shock from a
      pulmonary source (48%, 39/81) compared with diabetics (25%, 8/32) (p = .02).
      Forty-one percent (46/113) of the patients with septic shock developed ARDS.
      Forty-seven percent of the nondiabetic patients developed ARDS compared with only
      25% of those with diabetes (p = .03, relative risk = 0.53, 95% confidence
      interval = 0.28-0.98). In a multivariate logistic regression analysis, when we
      adjusted for several variables including source of infection, the effect of
      diabetes on the incidence of ARDS remained significant (p = .03, odds ratio =
      0.33, 95% confidence interval = 0.12-0.90). CONCLUSIONS: In patients with septic
      shock, a history of diabetes is associated with a lower risk of developing ARDS
      compared with nondiabetics.

PMID- 10921540
TI  - Multiple organ dysfunction syndrome: exploring the paradigm of complex nonlinear
      systems.
AB  - OBJECTIVES: The objectives of this article are to introduce and explore a novel
      paradigm based on complex nonlinear systems, and to evaluate its application to
      critical care research regarding the systemic host response and multiple organ
      dysfunction syndrome (MODS). DATA SOURCES: Published original work, review
      articles, scientific abstracts and books, as well as our personal files. STUDY
      SELECTION: Studies were selected for their relevance to the applications of
      nonlinear complex systems, to critical care medicine, and to the concepts
      presented. DATA EXTRACTION: We extracted all applicable data. DATA SYNTHESIS:
      Following a brief review of MODS, an introduction to complex nonlinear systems is
      presented, including clear concepts, definitions, and properties. By examining
      the multiple, nonlinear, interrelated, and variable interactions between the
      metabolic, neural, endocrine, immune, and inflammatory systems; data regarding
      interconnected antibody networks; and the redundant, nonlinear, interdependent
      nature of the inflammatory response, we present the hypothesis that the systemic
      host response to trauma, shock, or sepsis must be evaluated as a complex
      nonlinear system. This model provides a new explanation for the failure of trials
      using various antimediator therapies in the treatment of patients with sepsis and
      MODS. Understanding the host response as a complex nonlinear system offers
      innovative means of studying critical care patients, specifically by suggesting a
      greater focus on systemic properties. We hypothesize that analysis of variability
      and connectivity of individual variables offer a novel means of evaluating and
      differentiating the systemic properties of a complex nonlinear system. Current
      applications of evaluating variability and connectivity are discussed, and
      insights regarding future research are offered. CONCLUSION: The paradigm offered
      by the study of complex nonlinear systems suggests new insights to pursue
      research to evaluate, monitor, and treat patients with MODS.

PMID- 10921541
TI  - Prostaglandin E1 reduces myocardial reperfusion injury by inhibiting
      proinflammatory cytokines production during cardiac surgery.
AB  - OBJECTIVE: To determine the influence of prostaglandin E1 (PGE1) on the cytokine
      balance and myocardial protection during cardiac surgery. DESIGN: Prospective,
      randomized, nonblinded study. SETTING: University hospital. PATIENTS: A total of
      19 patients on cardiopulmonary bypass undergoing cardiac surgery. INTERVENTIONS:
      According to randomized sequence, the patients received PGE1 (0.02 approximately
      0.05 microg x kg(-1) x min(-1)) from the beginning of surgery to the end of study
      (PGE1 group, n = 11) or nothing (control group, n = 8). MEASUREMENTS AND MAIN
      RESULTS: Interleukin (IL)-6, IL-8, IL-10, IL-1 receptor antagonist (IL-1ra),
      soluble tumor necrosis factor receptor I (sTNF RI), and soluble tumor necrosis
      factor receptor II (sTNF RII) were measured by enzyme-linked immunosorbent
      assays. Troponin-T and isoenzyme of creatine kinase with muscle and brain
      subunits (CK-MB) were measured by enzyme immunoassay and ultraviolet absorption
      spectrophotometry method, respectively. Serum IL-6 and IL-8 concentrations in
      both groups increased significantly from 60 mins after declamping the aorta
      compared with preoperative value (p < .001), However, the increases were greater
      in the control group than in the PGE1 group (p < .01). Serum IL-10, IL-1ra, sTNF
      RI, and sTNF RII concentrations increased significantly from 60 mins after
      declamping the aorta compared with preoperative values in two groups (p < .001,
      respectively). There were no differences between the two groups. Serum troponin T
      and CK-MB concentrations increased significantly in the two groups from 60 mins
      after declamping the aorta (p < .001), but these increases were greater in the
      control group than in the PGE1 group (p < .01). IL-6 and IL-8 levels correlated
      with CK-MB concentration (r2 = 0.49, r2 = 0.36; p > .001 respectively).
      CONCLUSIONS: PGE1 suppressed the production of IL-6 and IL-8 but not IL-10, IL
      1ra, sTNF RI, or sTNF RII. The change in the balance between pro-and anti
      inflammatory cytokines may be one of the most important cytoprotective mechanisms
      of PGE1.

PMID- 10921543
TI  - Intestinal absorption in patients after cardiac surgery.
AB  - OBJECTIVES: We designed this study to assess intestinal absorption in patients
      with adequate or altered hemodynamic status after cardiac surgery and to test
      clinical tolerance to early enteral nutrition. DESIGN: Prospective, descriptive
      study. SETTING: Surgical intensive unit in a university teaching hospital.
      PATIENTS: Cardiac surgery patients, age 64+/-10 yrs (mean +/-SD) were subdivided
      into two groups according to hemodynamic status: group I, 16 patients with
      adequate hemodynamic status; group II, 23 patients with hemodynamic failure.
      These groups were compared with healthy controls (group III, n = 6).
      INTERVENTIONS: Paracetamol pharmacokinetic study on days 1 and 3 with nasogastric
      or postpyloric paracetamol administration. Early postpyloric or conventional
      gastric nutrition in group II. MEASUREMENTS AND MAIN RESULTS: Plasma
      concentrations were measured on days 1 and 3, and area under the curve (AUC) was
      calculated. Absorption was strongly reduced on day 1 in all patients after
      gastric administration (lower peak paracetamol and AUC), but normal after
      postpyloric delivery. Duration of anesthesia and of circulatory bypass did not
      affect paracetamol absorption. On day 3, AUC was close to normal in case of
      hemodynamic failure. Peak absorption on day 1 was negatively correlated with
      opiate dose (r2 = 0.176, p = .008). Hypocaloric enteral nutrition was well
      tolerated. CONCLUSIONS: The close-to-normal AUC, during low cardiac output,
      despite lower peak paracetamol, shows absorption was not suppressed, only
      delayed, because of decreased pyloric motility. The decrease on day 1 can be
      attributed to opiates, known to alter pyloric function and to slow down the
      intestinal transit.

PMID- 10921542
TI  - Prognostic value of protein C concentrations in neutropenic patients at high risk
      of severe septic complications.
AB  - OBJECTIVE: To assess the prognostic value of protein C, endogenous activated
      protein C, and D-dimer concentrations in patients at high risk of developing
      severe septic complications secondary to cytostatic chemotherapy. DESIGN:
      Prospective, comparative, single-center study. SETTING: Specialized ward for
      treating patients with acute leukemia and associated intensive care unit at a
      university hospital. SUBJECTS: Twenty-six consecutive patients who developed
      either severe sepsis (n = 13) or septic shock (n = 13) during chemotherapy
      induced neutropenia (leukocytes <1,000/microL). INTERVENTION: None, other than
      standard care. MEASUREMENTS AND MAIN RESULTS: Baseline blood samples were
      obtained from 97 adult patients treated with intensive cytostatic chemotherapy.
      Serial blood sampling was performed in 62 of 97 patients who developed fever
      (>38.3 degrees C). Thirteen patients progressed to severe sepsis and 13 patients
      to septic shock. Protein C, endogenous activated protein C, and D-dimer were
      measured in these 26 patients. At fever onset, protein C concentrations decreased
      from normal baseline concentrations and were significantly lower in the group of
      patients who progressed to septic shock compared with those who developed severe
      sepsis (medians for protein C activity: 23.1% vs. 69.5%; p = .0003). The median
      elapsed time between detection of fever and the diagnosis of severe sepsis or
      septic shock was 16 hrs and 12 hrs, respectively. All septic shock patients died,
      whereas patients who progressed only to severe sepsis survived. CONCLUSIONS:
      Septic shock in neutropenic patients is associated with increased protein C
      consumption. The data demonstrate that the coagulation cascade is activated and
      produces a hypercoagulable state before the onset of clinical symptoms of severe
      sepsis and septic shock. Low protein C concentrations at the onset of fever and
      before the onset of clinical symptoms of severe sepsis or septic shock may have
      prognostic value in predicting an unfavorable outcome. Protein C measurements may
      help identify patients at risk in an early phase of neutropenic sepsis. It is
      also attractive to speculate that because low protein C concentrations were seen
      in these patients, protein C replacement may be beneficial in sepsis.

PMID- 10921545
TI  - Limitations of the transpulmonary indicator dilution method for assessment of
      preload changes in critically ill patients with reduced left ventricular
      function.
AB  - OBJECTIVE: We examined whether intrathoracic blood volume (ITBV) and total end
      diastolic volume (TEDV), determined by the transpulmonary indicator dilution
      technique, adequately reflect preload changes during fluid administration in
      patients with reduced left ventricular function. DESIGN: A prospective,
      controlled, clinical study. SETTING: Medical intensive care unit in a university
      hospital. PATIENTS: A total of 18 sedated, mechanically ventilated, and
      moderately hypovolemic intensive care unit patients, eight with reduced left
      ventricular function (ejection fraction area, 24.9+/-8.0%, group A), ten with
      normal left ventricular function (ejection fraction area, 57.6+/-13.0%, group B).
      INTERVENTIONS: Continuous crystalloid infusion over 120 mins at a constant rate
      of 8 mL/kg/30 mins. MEASUREMENTS AND MAIN RESULTS: Stroke volume index, central
      venous pressure, pulmonary artery occlusion pressure (PAOP), TEDV, and ITBV were
      determined simultaneously at baseline and serially every 30 mins during
      continuous crystalloid infusion. A similar series of measurements was obtained
      during control conditions. Performance of various variables during fluid
      administration was assessed by time correlation analysis. Sensitivity for various
      variables defined as the ability to detect increasing amounts of administered
      fluid in individual patients was calculated. All examined variables increased
      during fluid administration and were unaffected during the control period. Mean
      time correlation (r2) was significantly higher for pressure monitoring (central
      venous pressure, r2 = 0.8281; PAOP, r2 = 0.5476) than for volume variables (TEDV,
      r2 = 0.0256; ITBV, r2 = 0.0729) in group A and was high for all variables in
      group B (central venous pressure, r2 = 0.7056; PAOP, r2 = 0.6241; TEDV, r2 =
      0.49; ITBV, r2 = 0.4225). Sensitivities for central venous pressure, PAOP, TEDV,
      and ITBV after 120 min were 63%, 75%, 25%, and 25% in group A and 90%, 100%, 60%,
      and 60% in group B, respectively. CONCLUSION: This study demonstrates limitations
      of the transpulmonary indicator dilution technique for monitoring of
      intravascular volume in patients with reduced left ventricular function.

PMID- 10921544
TI  - Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the
      intensive care unit with pulmonary infiltrates.
AB  - OBJECTIVE: To analyze the impact of fiberoptic bronchoscopy and bronchoalveolar
      lavage (BAL) on guiding the treatment and intensive care unit (ICU) clinical
      outcome in neutropenic patients with pulmonary infiltrates admitted to the ICU.
      DESIGN: Prospective collection of data. SETTING: Medical ICU in a teaching
      hospital. PATIENTS: During a 6-yr period, we analyzed the results of 93
      fiberoptic bronchoscopies plus BALs performed in 93 consecutive neutropenic ICU
      patients. We separated the patients into two groups according to the cause of
      neutropenia (high-dose chemotherapy [n = 41] or stem cell transplantation [SCT; n
      = 52]). RESULTS: Of the 93 BALs, 53 were performed to evaluate diffuse
      infiltrates and 42 were performed on mechanically ventilated patients. Forty-nine
      percent of BALs (46 patients) were diagnostic, with a significantly better yield
      in ICU patients with high-dose chemotherapy-induced neutropenia (26 of 41 BALs).
      The number of cases of proven infectious pneumonia was significantly higher in
      this group of ICU neutropenic patients. In patients who underwent SCT, diffuse
      infiltrates were statistically correlated with a negative result of BAL. Twenty
      six patients who underwent diagnostic BALs changed therapy. Sixteen complications
      (17%) occurred with only two intubations. The overall mortality rate in the ICU
      and the mortality rate in mechanically ventilated neutropenic patients were 71%
      and 93%, respectively. In neutropenic patients who underwent SCT, the mortality
      rate was statistically higher in patients in whom no diagnosis was established.
      Patients who had a diagnostic BAL that changed therapy did not have an increased
      probability of survival compared with patients who had a BAL that did not change
      therapy. CONCLUSIONS: The use of routine diagnostic BAL in ICU neutropenic
      patients with pulmonary infiltrates is difficult to establish, even if BAL is
      helpful in the management of these critically ill patients. BAL in our ICU
      neutropenic patient population had an acceptable overall diagnostic yield (49%),
      which was higher in ICU patients with chemotherapy-induced neutropenia.
      Nevertheless, in the ICU, if BAL had a low complication rate, it had infrequently
      led to changed treatment and was not associated with improved patient survival.

PMID- 10921546
TI  - Using a severity of illness scoring system to assess intensive care unit
      admissions for diabetic ketoacidosis.
AB  - OBJECTIVE: To determine the appropriateness of intensive care unit (ICU)
      admissions for patients with the diagnosis of diabetic ketoacidosis (DKA) at our
      institution. DESIGN: Retrospective chart review. SETTING: Tertiary care inner
      city hospital. SUBJECTS: All subjects admitted to the medical intensive care unit
      (MICU) from September 1996 to June 1997 with a diagnosis of DKA were included.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A grading system for the
      severity of DKA (grades 0-IV) from a previously published work was modified.
      Admissions to the MICU that were deemed appropriate a priori included patients
      with grade III or IV DKA, patients with grade II DKA who were older than 65 yrs
      of age, or patients with special situations normally warranting intensive care.
      MAIN RESULTS: Sixty-seven cases of DKA were reviewed. Two thirds of the patients
      had type I diabetes mellitus, and approximately 50% were men. No deaths occurred.
      Forty-four patients (66%) met the a priori ICU admission criteria. The average
      hospital stay for all patients was 4.2 (+/-3.6) days. The mean ICU stay was
      significantly longer in those with DKA grade III or IV, although the total
      hospital stay did not differ by severity of illness score. CONCLUSIONS: One third
      of the patients admitted to our MICU to receive treatment for DKA did not warrant
      ICU treatment based on the admission criteria. These individuals had an
      approximate MICU length of stay of 1 day. A prospective study of the severity of
      illness score will be undertaken to evaluate the safety, validity, and potential
      resource savings of applying these DKA ICU admission criteria within our
      institution.

PMID- 10921547
TI  - Effects of guidelines implementation in a surgical intensive care unit to control
      nighttime light and noise levels.
AB  - OBJECTIVE: Because of around-the-clock activities, environmental noise and light
      are among the many causes of sleep disturbance in an intensive care unit (ICU).
      The implementation of guidelines may potentially change behavior rules and
      improve sleep quality. DESIGN: A prospective interventional study, observing the
      effects of simple nighttime guidelines on light and noise levels in an ICU.
      SETTING: A modern surgical ICU, subdivided into six identical three-bed rooms.
      PATIENTS: Critically ill adult patients. INTERVENTION: Between two observation
      periods, five guidelines were implemented to decrease both light and noise during
      the night shift in the patient's room. MEASUREMENT: Light levels and noise levels
      were obtained using a luxmeter and a sound level meter [A-weighted decibels (dB)
      scale] and were monitored continuously from 11 pm to 5 am both before (period P1)
      and after (period P2) the implementation of guidelines. MAIN RESULTS: Similar
      patient's gravity and nursing workload scores were observed between P1 and P2. A
      low mean (<5 Lux) and maximal light level were measured during both P1 and P2.
      The implementation of guidelines lowered mean light disturbance intensity with a
      greater variability of light during P2. All noise levels were high and
      corresponded more to a quiet office for noise level equivalents and to a busy
      restaurant for peak noise levels during both P1 and P2. Guidelines decreased the
      noise level equivalent (P1, 51.3 dB; P2, 48.3 dB), peak noise level (P1, 74.9 dB;
      P2, 70.8 dB), and the number of acoustic identified alarms (P1, 22.1 dB; P2, 15.8
      dB) during P2. CONCLUSION: The night light levels were low during both periods,
      and lowering the light levels induced a greater variation of light, which may
      impair sleep quality. All measured noise levels were high during both periods,
      which could contribute to sleep disturbance, and the implementation of guidelines
      significantly lowers some important noise levels. The background noise level was
      unchanged.

PMID- 10921548
TI  - Transcutaneous oxygen and CO2 as early warning of tissue hypoxia and hemodynamic
      shock in critically ill emergency patients.
AB  - BACKGROUND: Although cardiac and pulmonary function can be measured precisely,
      evaluation of tissue perfusion remains elusive because it usually is inferred
      from subjective symptoms and imprecise signs of shock. The latter are indirect
      criteria used to assess the overall circulatory status as well as tissue
      perfusion but are not direct quantitative measures of perfusion. However,
      noninvasive transcutaneous oxygen (PtcO2) and carbon dioxide (PtcCO2) tensions,
      which directly measure skin oxygenation and CO2 retention, may be used to
      objectively evaluate skin oxygenation and perfusion in emergency patients
      beginning with resuscitation immediately after hospital admission. OBJECTIVE:
      This study was a preliminary evaluation of tissue oxygenation and perfusion by
      objective PtcO2 and PtcCO2 patterns in severely injured surviving and
      nonsurviving patients; specifically, the aim was to describe time patterns that
      may be used as early warning signs of circulatory dysfunction and death. DESIGN:
      Prospective descriptive study of a consecutive series of severely injured
      emergency patients. SETTING: University-affiliated Level I trauma center and
      intensive care unit. PATIENTS AND METHODS: Forty-eight consecutive severely
      injured patients were prospectively monitored by PtcO2 and PtcCO2 sensors
      immediately after emergency admission. RESULTS: Compared with survivors, patients
      who died had significantly lower PtcO2 and higher PtcCO2 values beginning with
      the early stage of resuscitation. All patients who maintained PtcO2 >150 torr
      (19.99 kPa) throughout monitoring survived. Periods of PtcO2 <50 torr (6.66 kPa)
      for >60 mins or PtcCO2 >60 torr (8.00 kPa) for >30 mins were associated with 90%
      mortality and 100% morbidity. CONCLUSION: PtcO2 and PtcCO2 monitoring
      continuously evaluate tissue perfusion and serve as early warning in critically
      injured patients during resuscitation immediately after hospital admission.

PMID- 10921549
TI  - Volume expansion using pentastarch does not change gastric-arterial CO2 gradient
      or gastric intramucosal pH in patients who have sepsis syndrome.
AB  - OBJECTIVE: In hypovolemic patients with sepsis syndrome, to determine the effects
      of colloid volume infusion using 10% pentastarch on abnormal gastric tonometer
      measurements (gastric intramucosal CO2 tension, gastric intramucosal-arterial
      PCO2 gradient, and gastric intramucosal pH [pHi]) and on cardiac index, global
      oxygen delivery, and hemoglobin. DESIGN: Prospective prepost intervention study.
      SETTING: Tertiary care, university-affiliated 15-bed general systems intensive
      care unit. PATIENTS: Patients were studied who had sepsis syndrome, who had
      pulmonary arterial catheters in place, who were hypovolemic (pulmonary arterial
      occlusion pressure [PAOP] <15 mm Hg), and who had a gastric arterial PCO2
      gradient >10 mm Hg. INTERVENTIONS: Baseline measurements of gastric intramucosal
      CO2 tension, gastric intramucosal-arterial PCO2 gradient, and pHi, as well as
      arterial lactate, pulmonary arterial occlusion, central venous and systemic
      arterial pressures, thermodilution cardiac output, and temperature. Boluses of
      500 mL pentastarch were administered to a total of 1,000 mL or until PAOP was >18
      mm Hg. Measurements were repeated at 30 mins and 120 mins postinfusion of
      pentastarch. MAIN RESULTS: Volume infusion using pentastarch did not change
      gastric PCO2, gastric-arterial PCO2 gradient, or pHi. Volume expansion with
      pentastarch significantly increased cardiac index, global oxygen delivery, and
      PAOP. Administration of pentastarch decreased hemoglobin and arterial lactate at
      30 mins but not at 120 mins. CONCLUSIONS: Volume expansion using a colloidal
      solution of 10% pentastarch does not change abnormal intramucosal CO2 tension,
      gastric-arterial PCO2 gradient, or pHi in critically ill hypovolemic patients who
      have sepsis syndrome despite increasing cardiac index, oxygen delivery, and
      pulmonary artery occlusion pressure.

PMID- 10921550
TI  - The weaning continuum use of Acute Physiology and Chronic Health Evaluation III,
      Burns Wean Assessment Program, Therapeutic Intervention Scoring System, and Wean
      Index scores to establish stages of weaning.
AB  - OBJECTIVE: To determine whether four stages of weaning (acute, prewean, wean, and
      outcome) could be identified by using clinical instruments designed to quantify
      severity of illness, patient stability, or weaning readiness. The instruments
      used were the Acute Physiology and Chronic Health Evaluation (APACHE III), the
      Therapeutic Intervention Scoring System (TISS), the Burns Wean Assessment Program
      (BWAP), and the Wean Index (WI). The stages were adapted from those proposed by
      the American Association of Critical Care Nurses Third National Study Group's
      Weaning Continuum Model. DESIGN: Prospective, convenience cohort. This study was
      part of a larger study designed to test an outcomes managed approach to weaning
      by using an outcomes manager and a clinical pathway. SETTING: University medical
      intensive care unit. PATIENTS: Adult patients requiring mechanical ventilation >3
      days admitted to the medical intensive care unit between November 1994 and May
      1995. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Scores for the APACHE
      III, TISS, BWAP, and WI were collected on 97 patients every other day until they
      weaned, were transferred, or died. Outcomes described for each stage of weaning
      were dated on the clinical pathway when achieved. Comments about patient
      stability and ventilator progress also were recorded along with a subjective
      determination of the stage of weaning. We used decision rules to identify time
      intervals for each stage of weaning and outcomes attained by stage. Finally,
      APACHE III, TISS, BWAP, and WI scores were placed in each stage by date for
      analysis. The APACHE III, TISS, and BWAP scores were able to differentiate the
      acute, prewean, and wean stages but not the outcome stage. CONCLUSIONS: By
      identifying distinct scores for each stage, we may be able to better explore
      appropriate interventions for the stages as well as predict weaning outcomes.
      Indices that include physiologic and respiratory factors can differentiate
      weaning stages, but respiratory factors alone cannot.

PMID- 10921551
TI  - Transesophageal versus surface pulse oximetry in intensive care unit patients.
AB  - OBJECTIVES: To compare oximetric readings from the esophagus (STEO2) and the skin
      (finger, SSO2) with those obtained from arterial blood samples (SaO). In
      addition, to compare the influences of mean arterial pressure (MAP) and body
      temperature to the accuracy of STEO2 and SSO2 readings. DESIGN: Prospective,
      single-center study. SETTING: Surgical intensive care unit of an academic,
      teaching, and community hospital in Austria. PATIENTS: A total of 40 consecutive,
      severely traumatized or diseased, intensive care unit patients requiring
      mechanical ventilatory support and deep analgosedation. Patients had to be
      nonpregnant, > or =19 yrs of age, and without a disease or a trauma of the
      esophagus. INTERVENTIONS: Placement of an esophageal and a finger-pulse oximetry
      probe and a radial artery catheter. MEASUREMENTS AND MAIN RESULTS: STEO2, SSO2,
      MAP, and esophageal temperature were recorded continuously during a 4-hr period,
      and SaO2 was measured every 30 mins. The first outcome variable was the deviation
      of STEO2 and SSO2 from SaO2. The second outcome variable was the influence of MAP
      and body temperature on STEO2 and SSO2 regression analysis and repeated measures.
      Analysis of variance was used for statistics (p < .05 was accepted as
      significant). In patients with a MAP ranging from 29 to 111 mm Hg and a
      temperature ranging from 33.4 degrees C (92.1 degrees to 39.2 degrees C (102.6
      degrees F), SSO2 measurements underestimate SaO2 by 2% to 4%. Whereas STEO2
      matches SaO2, STEO2 was not dependent on MAP or temperature, but increased
      temperature or low MAP were associated with falsely low SSO2 readings.
      CONCLUSIONS: Assuming correct positioning of the probe, readings from the
      esophagus are more consistent with arterial oxygen saturation than readings from
      surface pulse oximetry. MAP or temperature changes do not influence STEO2, but
      they do affect SSO2. In critically ill patients, STEO2 appears to be a more
      reliable variable than SSO2.

PMID- 10921552
TI  - Acute respiratory distress syndrome secondary to cardiopulmonary bypass: do
      compromised plasma iron-binding anti-oxidant protection and thiol levels
      influence outcome?
AB  - OBJECTIVES: Cardiopulmonary bypass (CPB) surgery is often associated with mild
      lung injury and in some patients leads to acute lung injury and acute respiratory
      distress syndrome (ARDS). Aberrant plasma iron chemistry (increased iron loading
      of transferrin and/or the presence of redox-active low molecular mass iron) and
      increased plasma thiol levels are features of this type of surgery and represent
      a potential pro-oxidant risk for oxidative damage. Oxidative damage is a feature
      of ARDS, and we hypothesized that pro-oxidant forces may contribute to the onset
      and progression of ARDS. DESIGN: Prospective, single center, observational study.
      SETTING: University-affiliated tertiary referral cardiothoracic center. PATIENTS:
      A total of 19 patients with ARDS secondary to CPB surgery and 64 patients with
      ARDS secondary to a variety of other predisposing causes. INTERVENTIONS:
      Supportive techniques appropriate to the treatment of ARDS. MEASUREMENTS AND MAIN
      RESULTS: Blood samples were collected into lithium heparin tubes for all patient
      groups on the first day of the admission of patients to the intensive care unit
      immediately after the diagnosis of ARDS. Plasma was immediately assayed for thiol
      content and total protein and albumin levels. Plasma from patients with ARDS
      secondary to CPB surgery was also assayed for changes in iron chemistry.
      Nonsurviving patients with ARDS secondary to CPB surgery displayed significantly
      greater levels of aberrant iron chemistry (elevated levels of iron saturation of
      transferrin) with decreased iron-binding antioxidant protection and elevated
      plasma thiol levels than did survivors. Plasma thiol levels in patients with ARDS
      secondary to other predisposing causes were (with the exception of lung-surgery
      patients) significantly elevated in survivors compared with those in nonsurvivors
      of the syndrome. CONCLUSIONS: Increased levels of plasma thiol appear to be
      associated with mortality in patients with ARDS secondary to CPB surgery.

PMID- 10921553
TI  - Interleukin-1 receptor antagonist production during infectious and noninfectious
      systemic inflammatory response syndrome.
AB  - OBJECTIVE: To analyze the levels of circulating and cell-associated forms of
      interleukin-1 receptor antagonist (IL-1ra) and the spontaneous and the
      lipopolysaccharide- or streptococcus-induced ex vivo production of IL-1ra by
      isolated neutrophils. DESIGN: Cohort study. SETTING: A collaborative study
      between an intensive care unit and a research laboratory. PATIENTS: Septic
      patients (those with infectious systemic inflammatory response syndrome [SIRS])
      and patients undergoing cardiac surgery with cardiopulmonary bypass
      (noninfectious SIRS). MEASUREMENTS AND MAIN RESULTS: Both noninfectious and
      infectious SIRS patients had enhanced levels of plasma IL-1ra. In septic
      patients, the increased level of IL-1ra associated with circulating leukocytes
      reflected the higher number of circulating neutrophils, because these cells, as
      well as peripheral blood mononuclear cells, contained similar levels of cell
      associated forms of IL-1ra than those found at homeostasis in healthy controls.
      The analysis of the in vitro production of IL-1ra by neutrophils showed a
      decreased capacity of these cells to release the secreted form of IL-1ra on
      activation in all patients when compared with that capacity in healthy controls.
      In contrast, the production of the intracellular forms of IL-1ra was not altered
      in septic patients, but it was diminished in post-cardiopulmonary bypass
      patients. CONCLUSIONS: The capacity of releasing IL-1ra by activated neutrophils
      from infectious or noninfectious SIRS patients was diminished. In contrast, the
      accumulation of intracellular IL-1ra in septic patients was not modified when
      compared with that in healthy controls. These ex vivo data illustrate that a
      different gene regulation of the secreted and intracellular forms of IL-1 ra
      occurs during a pathologic situation like sepsis.

PMID- 10921554
TI  - A phase I study of oxidized raffinose cross-linked human hemoglobin.
AB  - OBJECTIVE: To evaluate the safety of oxidized-raffinose cross-linked human
      hemoglobin, Hemolink, in normal healthy volunteers. DESIGN: Randomized, placebo
      controlled, double-blind study. SETTING: Clinical research facility of a contract
      research organization. PATIENTS: Forty-two healthy adult male volunteers of which
      33 received Hemolink. INTERVENTIONS: Oxidized-raffinose cross-linked and
      polymerized hemoglobin as a 10% (w/v) solution, in doses of 0.025-0.6 g/kg or an
      equivalent volume of lactated Ringer's solution, was infused intravenously on day
      1, and subjects were monitored for 3 days in the clinical facility with < or =6
      wks follow-up. Major organ function was assessed pre- and postinfusion, by
      hemodynamic, electrocardiographic, pulmonary function, and clinical chemistry
      measurements. MEASUREMENTS AND MAIN RESULTS: Doses of 1.7-42 g of hemoglobin were
      administered with no serious adverse events noted. Abdominal pain of moderate to
      severe intensity was seen in some subjects at doses >0.4 g/kg and was alleviated
      with smooth muscle relaxants. There was a dose-dependent increase in mean
      arterial pressure with a plateau of approximately 14% above baseline at 0.1 g/kg.
      There was a concomitant reduction in heart rate, with no electrocardiographic
      abnormalities found. Respiratory function was not affected. There was a dose
      dependent increase in serum bilirubin with values above the upper limit of normal
      at doses of > or =0.4 g/kg. Small increases in aspartate aminotransferase and
      alanine aminotransferase were noted in some patients, whereas alkaline
      phosphatase and gamma-glutamyltransferase remained in the normal range. Serum
      amylase concentrations were normal in 31 of 33 patients receiving Hemolink,
      whereas lipase was within the normal range in 21 of 33 patients. LDH was
      increased in a dose-dependent fashion. Two patients had increased creatine kinase
      concentrations, with a normal creatine kinase-MB mass fraction. All hematologic
      variables were within the normal range. The half-life of the oligomeric (>64 kDa)
      fraction of Hemolink was 18-20 hrs. CONCLUSION: Oxidized-raffinose cross-linked
      hemoglobin, Hemolink, at doses < or =0.6 g/kg were well tolerated in healthy
      volunteers with no evidence of organ dysfunction. Further investigation of its
      potential use in surgical and trauma settings appears warranted.

PMID- 10921555
TI  - Survival, morbidity, and quality of life after discharge from intensive care.
AB  - OBJECTIVE: To assess survival, morbidity (physical and psychological), quality of
      life (QOL), and employment status of intensive care survivors up to 12 months
      after discharge from the intensive care unit (ICU). DESIGN: Prospective study.
      SETTING: University hospital adult ICU. PATIENTS: Between August 1, 1995, and
      July 31, 1996, 370 patients were admitted. Of these patients, 29% died in the
      ICU. Three months after discharge from the ICU, 227 patients were alive, and 143
      agreed to participate. Cumulative mortality was calculated using the original
      complete cohort. MEASUREMENTS AND MAIN RESULTS: Demographic data, severity of
      acute illness (Acute Physiology and Chronic Health Evaluation [APACHE] II),
      admitting specialty, primary diagnosis, and length of stay were recorded.
      Physical and ICU-related psychological morbidity (Hospital Anxiety and Depression
      scale score) were recorded. Health-related QOL was assessed using the Short-Form
      36. All the questionnaires were completed in the clinic at 3 months. Assessment
      of physical morbidity and employment status at 6 and 12 months were conducted by
      telephone. The cumulative mortality was 39% at 3 months, 41% at 6 months, and 43%
      at 12 months. Deaths after 3 months occurred in the group who refused follow-up.
      The median age for the follow-up group was 51 yrs; the gender split was 68 women
      and 75 men; the mean admission APACHE II score was 18.79 (SD 6.15); and the
      median length of ICU stay was 3.8 days. At 3 months, approximately 80% of all
      patients interviewed were satisfied with their QOL. Older men (>65 yrs) and
      younger women (<65 yrs) demonstrated significantly better health with respect to
      some subdomains of the Short-Form 36 compared with their counterparts. The
      prevalence of psychological distress (Hospital Anxiety and Depression scale
      score, > or =8) was low: 11.9% had heightened anxiety, and 9.8% were depressed.
      There were high levels of fatigue, poor concentration, and sleep disturbance; the
      latter was more marked in women (p = .022). Improvement in all three symptoms
      occurred during the next 9 months. Significantly more women reported loss of hair
      (p < .0001). Men were slower to return to employment; 75% of women had returned
      by 6 months compared with only 65% of men at 1 yr. CONCLUSION: Assessment of
      outcome after ICU stay must include QOL measurements. Three months after
      discharge, there is a low incidence of ICU-related psychological or psychiatric
      illness and the majority of patients are satisfied. Differences in the incidence
      and nature of morbidity exist between the genders.

PMID- 10921556
TI  - Pharmacoeconomic impact of rational use guidelines on the provision of analgesia,
      sedation, and neuromuscular blockade in critical care.
AB  - OBJECTIVE: To determine the cost-effectiveness and safety of a set of rational
      use guidelines for analgesia, sedation, and neuromuscular blockade in critically
      ill ventilated patients when compared with similar factors in standard
      prescribing. DESIGN: Prospective cost-benefit analysis. SETTING: Medical and
      surgical intensive care units (ICU) of a 350-bed tertiary care university
      hospital. PATIENTS: Patients admitted to our ICUs who required mechanical
      ventilation and continuous analgesics, sedatives, and/or neuromuscular junction
      blockers (NMJBs). There were 72 patients in the baseline and 84 patients in the
      follow-up groups. INTERVENTIONS: Prospective tracking of eligible baseline
      patients was followed by the development and introduction of guidelines and an
      academic detailing process to promote the use of guidelines. Several months after
      the introduction of guidelines, a second group of eligible follow-up patients was
      tracked. The use and effectiveness of analgesics, sedatives, and NMJBs, as well
      as cost and outcomes, were followed in both groups. Data were subsequently
      reviewed and analyzed. MEASUREMENTS AND MAIN RESULTS: We recorded data by means
      of Paradox and Excel databases and included demographics, costs, outcomes
      (including adverse drug reactions, functional status, ventilator time in hours,
      lengths of stay), and mortality rates. Data were subsequently analyzed via the
      Winks statistical data analysis program. Both groups were similar with regard to
      demographics. There was a statistically significant increase in severity of
      illness in the follow-up group without a statistically significant increase in
      mortality. Direct drug costs, ventilator time, and lengths of stay were reduced
      in the follow-up group. In addition, the use of NMJBs was reduced from 30% in the
      baseline group to 5% in the follow-up group. CONCLUSIONS: Rational use guidelines
      resulted in safe, cost-effective improvements in the provision of continuous
      analgesia, sedation, and neuromuscular blockade to critically ill patients
      requiring ventilator management when compared with similar factors in baseline
      prescribing strategies.

PMID- 10921557
TI  - Energy expenditure in 100 ventilated, critically ill children: improving the
      accuracy of predictive equations.
AB  - OBJECTIVE: The purpose of this study was to evaluate current methods of
      predicting energy requirements and to develop and validate new equations derived
      from energy expenditure measurements of ventilated, critically ill children.
      DESIGN: Prospective, observational, sequential study. SETTING: Pediatric
      intensive care unit. PATIENTS: A total of 100 ventilated, critically ill children
      who fit the criteria of energy expenditure measurement. Additional patients (n =
      25) were included in the validation study. INTERVENTION: An indirect calorimeter
      was used to measure energy expenditure for a period of 30 mins. MEASUREMENTS AND
      MAIN RESULTS: The mean measured energy expenditure was 185+/-51 kJ/kg per day.
      Predicted energy expenditure from standard equations was compared with measured
      energy expenditure by using the Bland and Altman "methods comparison procedure,"
      and poor precision and accuracy were observed. Patient variables were collected
      at the time of measurement, and multiple regression analysis was performed to
      determine the independent contribution of each variable to measure energy
      expenditure. New predictive equations were formulated and validated with
      additional energy expenditure measurements. Patient variables that did not
      correlate significantly with energy expenditure were gender, Pediatric Risk of
      Mortality score, and commencement of nutritional support. An equation was derived
      from patient variables (age, weight, weight for age Z score, body temperature,
      number of days after intensive care admission, and primary reason for admission)
      that correlated significantly (r2 = .898) with measured energy expenditure. A
      second, simplified equation (energy expenditure kJ/day = ?17 x age [months]? +
      ?48 x weight [kg]? + ?292 x body temperature degrees C? - 9,677) was produced (r2
      = .867). Validation found no significant difference between measured and
      predicted energy expenditure by the new equations; however, the equations did not
      predict accurately for patients <2 months of age. CONCLUSION: The new equations
      provide a more accurate alternative to current predictive methods in assessing
      energy requirements of ventilated, critically ill children.

PMID- 10921558
TI  - Stress test and gastric-arterial PCO2 measurement improve prediction of
      successful extubation.
AB  - OBJECTIVE: Correct early prediction of successful extubation decreases morbidity
      and mortality. The use of single time point measurements and surrogate markers of
      true extubation success limits weaning studies. Our aim was to determine whether
      a "stress test" improves prediction of extubation outcome and to determine the
      most predictive variables. DESIGN: Observational study. SETTING: Intensive care
      unit of a teaching hospital. PATIENTS: A convenience sample of 68 patients judged
      to be ready for extubation. INTERVENTIONS: We decreased pressure support from 5
      to 0 cm H2O for 1 hr before extubation (stress test) while patients were on 5 cm
      H2O continuous positive airway pressure. MEASUREMENTS AND MAIN RESULTS: We
      measured respiratory frequency, tidal volume, ratio of respiratory frequency to
      tidal volume (f/VT), airway occlusion pressure after onset of inspiration (P0.1),
      and gastric-arterial PCO2 (deltaPg-aCO2 both on 5 cm H2O and 0 cm H2O pressure
      support. Then all patients were extubated. Failure of extubation was defined as
      reintubation within 24 hrs. Seventeen patients (25%) failed extubation. With
      pressure support of 5 cm H2O and continuous positive airway pressure of 5 cm H2O,
      most predictors were not different between patients who failed and patients who
      were successfully extubated. After the stress test, deltaPg-aCO2 was 2 (-5; 15)
      mm Hg (median; quartiles) in successfully extubated patients vs. 28 (-9; 48) in
      failures (p = .0003), tidal volume was 473 (387; 558) vs. 400 (323; 435) mL (p =
      .02), and P0.1 was 2.8 (2; 4.1) vs. 4.1 (2.7; 5.3) mm Hg (p = .03), respectively.
      The stress test increased specificity of deltaPg-aCO2 from 0.45 to 0.94 and
      positive predictive value from 0.85 to 0.97. The specificity and positive
      predictive values for f/VT after the stress test were 0.23 and 0.78. CONCLUSIONS:
      A simple stress test improves prediction of extubation outcome. deltaPg-aCO2 has
      superior specificity and positive predictive value compared with other variables.
      The use of true clinical outcome (i.e., extubation) instead of the use of
      surrogate markers (e.g., tachypnea) distinguishes these results from previous
      studies.

PMID- 10921559
TI  - Cardiopulmonary resuscitation of older, inhospital patients: immediate efficacy
      and long-term outcome.
AB  - OBJECTIVE: To determine the independent effect of advancing age on prognosis
      after cardiopulmonary resuscitation (CPR). DESIGN AND SETTING: Retrospective
      analysis of clinical records of patients who received CPR in a geriatric
      department equipped with an intensive care unit. PATIENTS: A total of 245
      patients (146 men, 99 women; mean age, 70+/-11 yrs) received CPR. Of these, 221
      had a cardiocirculatory arrest (CA) in the intensive care unit and 24 had a CA in
      the general ward of the department. Acute myocardial infarction was the most
      frequent admission diagnosis. INTERVENTIONS: CPR according to standard guidelines
      in all cases. MEASUREMENTS AND MAIN RESULTS: Immediate, short-term (hospital
      discharge), and long-term (median follow-up, 31.5 months; range, <1-124 months)
      survival. Older patients had a lower immediate survival (<70 yrs [72/137] 52.6%
      vs. > or =70 yrs [43/108] 39.4%; p < .05) and, less frequently, ventricular
      tachycardia/ fibrillation (VT/VF) as a cause of CA. VT/VF bore the lowest
      immediate mortality rate (19/104; 18.3%) as compared with asystole/complete heart
      block (66/102; 64.7%) or pulseless electrical activity (40/49; 81.6%; p < .001).
      Acute myocardial infarction, acute heart failure, hypotension, and occurrence of
      CA in the intensive care unit were also univariate predictors of unfavorable,
      immediate prognosis. However, in a multiple logistic analysis model, the
      mechanism of CA (asystole/complete heart block or pulseless electrical activity
      vs. VT/VF), acute myocardial infarction, heart failure, and hypotension were
      independent predictors of unfavorable immediate prognosis, whereas advancing age
      was not. Similarly, after initially successful CPR, short-term survival was
      independently associated with acute myocardial infarction, hypotension before CA,
      initial rhythm at CA, and need for mechanical ventilatory support after CPR, but
      not with age. Longterm survival (42 patients; 17.2% of the original cohort;
      median survival, 32 months) was also independent of age, whereas it was
      negatively associated with heart failure. CONCLUSION: Immediate, short- and long
      term prognosis after in hospital CPR is independent of age, at least when
      possible confounders are simultaneously taken into account.

PMID- 10921560
TI  - Keratinocyte growth factor and hepatocyte growth factor in bronchoalveolar lavage
      fluid in acute respiratory distress syndrome patients.
AB  - OBJECTIVES: To determine bronchoalveolar lavage (BAL) fluid concentrations of
      keratinocyte growth factor (KGF) and hepatocyte growth factor (HGF), two potent
      growth factors for alveolar type II epithelial cells, in patients with acute
      respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: An
      adult trauma/surgical intensive care unit in an urban teaching hospital.
      PATIENTS: A total of 32 ventilated patients with pulmonary infiltrates
      prospectively identified with ARDS (n = 17) or without ARDS (n = 15), including
      eight patients with hydrostatic edema (HE), and ten nonventilated patients
      serving as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: BAL was
      performed 2.88 days +/- 2.4, 3.5 days +/- 2.4, and 2.3 days +/- 2.2 after the
      lung insult in ARDS, HE, and other non-ARDS patients respectively (p = .32). KGF
      was detected in BAL fluid in 13 of the 17 ARDS patients (median, 31.6 pg/mL), in
      one patient with HE, and in none of other non-ARDS patients. In ARDS patients,
      detection of KGF in BAL was associated in BAL fluid with the detection of type
      III procollagen peptide (PIIIP), a biological marker of fibroproliferation. In
      ARDS patients, detection of KGF in BAL was associated with death (p = .02). HGF
      was detected in 15 ARDS patients (median, 855 pg/mL), in seven patients with HE
      (median, 294 pg/mL; p = .05 for the comparison with ARDS group), in six of other
      non-ARDS patients (median, 849 pg/mL; p = .32 with ARDS group). HGF
      concentrations were higher in nonsurvivors than in survivors (p = .01). None of
      the ten BAL of controls contained either KGF or HGF. CONCLUSION: KGF was detected
      almost exclusively in BAL fluid from ARDS patients and correlated with a poor
      prognosis in this group. In contrast, HGF was detected in the BAL fluid from a
      majority of patients with or without ARDS. Elevated HGF concentrations were
      associated with a poor prognosis in the overall group.

PMID- 10921561
TI  - Erythromycin improves gastric emptying in critically ill patients intolerant of
      nasogastric feeding.
AB  - OBJECTIVE: To evaluate the effect of intravenous erythromycin on gastric emptying
      and the success of enteral feeding in mechanically ventilated, critically ill
      patients with large volume gastric aspirates. DESIGN: Prospective, double-blind,
      randomized, and placebo-controlled trial. SETTING: General intensive care unit in
      a university hospital. PATIENTS: Twenty critically ill, mechanically ventilated
      patients intolerant of nasogastric feeding (indicated by a residual gastric
      volume of > or =250 mL during feed administration at > or =40 mL/hr).
      INTERVENTIONS: After a gastric aspirate of > or =250 mL, which was discarded, the
      enteral feeding was continued at the previous rate for 3 hrs. Intravenous
      erythromycin (200 mg) or placebo was then administered over 20 mins. The residual
      gastric contents were again aspirated and the volume was recorded 1 hr after the
      infusion began. MEASUREMENTS AND MAIN RESULTS: Gastric emptying was calculated as
      volume of feed infused into the stomach over 4 hrs minus the residual volume
      aspirated. Mean gastric emptying was 139+/-37 (+/-SEM) mL after erythromycin and 
      2+/-46 mL after placebo (p = .027). Nasogastric feeding was successful in nine of
      ten patients treated with erythromycin and five of ten who received placebo 1 hr
      after infusion (chi-square p = .05). CONCLUSION: In critically ill patients who
      have large volumes of gastric aspirates indicating a failure to tolerate
      nasogastric feeding, a single small dose of intravenous erythromycin allows
      continuation of feed in the short term.

PMID- 10921562
TI  - Differential effects of dopamine, dopexamine, and dobutamine on jejunal mucosal
      perfusion early after cardiac surgery.
AB  - OBJECTIVE: To evaluate the potential differential effects of dopamine,
      dopexamine, and dobutamine on jejunal mucosal perfusion, assessed by endoluminal
      laser Doppler flowmetry in uncomplicated postcardiac surgical patients. DESIGN: A
      prospective, blinded, randomized, crossover study. SETTING: A cardiothoracic
      intensive care unit in a tertiary care center. PATIENTS: A total of ten
      postoperative cardiac surgical patients were studied. INTERVENTIONS: Each patient
      received sequentially, randomly, and in a blinded fashion 2.7+/-0.2 microg x kg(
      1) x min(-1) dopamine, 0.7+/-0.1 microg x kg(-1) x min(-1) dopexamine, and 2.7+/
      0.1 microg x kg(-1) x min(-1) dobutamine. Each inotropic agent was titrated to
      increase cardiac output by 25% from baseline. Data on jejunal mucosal perfusion,
      splanchnic lactate, and oxygen extraction were obtained during a 5-min control
      period and a 5-min drug infusion period after the target cardiac output was
      reached. The procedure was sequentially repeated for each agent, and there was a
      20- to 30-min washout period between each agent. MEASUREMENTS AND MAIN RESULTS:
      Dopamine, dopexamine, and dobutamine increased jejunal mucosal perfusion by 27%
      (p < .01), 20% (p < .001), and 7% (p < .001), respectively. The increase in
      jejunal mucosal perfusion by dopamine and dopexamine were significantly more
      pronounced compared with dobutamine (p < .05 and p < .01, respectively), whereas
      there was no difference between dopamine and dopexamine. Splanchnic oxygen
      extraction decreased to the same extent with all three drugs. Splanchnic lactate
      extraction did not change for any of the drugs. The effects on central
      hemodynamics were similar for the three inotropic agents. CONCLUSIONS:
      Endoluminal laser Doppler flowmetry is a new tool for the detection of perfusion
      changes at the local intestinal mucosal level. Dopamine, dopexamine, and
      dobutamine have differential effects on jejunal mucosal perfusion probably
      because of their different receptor stimulating properties. These findings may be
      of clinical importance when the therapeutic goal is to improve gut mucosal
      perfusion.

PMID- 10921563
TI  - Plasma granulocyte colony-stimulating factor and granulocyte-macrophage colony
      stimulating factor levels in critical illness including sepsis and septic shock:
      relation to disease severity, multiple organ dysfunction, and mortality.
AB  - OBJECTIVE: To define the circulating levels of granulocyte colony-stimulating
      factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF)
      during critical illness and to determine their relationship to the severity of
      illness as measured by the Acute Physiology and Chronic Health Evaluation
      (APACHE) II score, the development of multiple organ dysfunction, or mortality.
      DESIGN: Prospective cohort study. SETTING: University hospital intensive care
      unit. PATIENTS: A total of 82 critically ill adult patients in four clinically
      defined groups, namely septic shock (n = 29), sepsis without shock (n = 17),
      shock without sepsis (n = 22), and nonseptic, nonshock controls (n = 14).
      INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: During day 1 of septic shock,
      peak plasma levels of G-CSF, interleukin (IL)-6, and leukemia inhibitory factor
      (LIF), but not GM-CSF, were greater than in sepsis or shock alone (p < .001), and
      were correlated among themselves (rs = 0.44-0.77; p < .02) and with the APACHE II
      score (rs = 0.25-0.40; p = .03 to .18). G-CSF, IL-6, and UF, and sepsis, shock,
      septic shock, and APACHE II scores were strongly associated with organ
      dysfunction or 5-day mortality by univariate analysis. However, multiple logistic
      regression analysis showed that only septic shock remained significantly
      associated with organ dysfunction and only APACHE II scores and shock with 5-day
      mortality. Similarly, peak G-CSF, IL-6, and LIF were poorly predictive of 30-day
      mortality. CONCLUSIONS: Plasma levels of G-CSF, IL-6, and LIF are greatly
      elevated in critical illness, including septic shock, and are correlated with one
      another and with the severity of illness. However, they are not independently
      predictive of mortality, or the development of multiple organ dysfunction. GM-CSF
      was rarely elevated, suggesting different roles for G-CSF and GM-CSF in human
      septic shock.

PMID- 10921564
TI  - Neutrophil deformability in patients with sepsis, septic shock, and adult
      respiratory distress syndrome.
AB  - OBJECTIVE: To investigate the deformability of morphologically active and passive
      neutrophils in patients with sepsis (SP), septic shock (SS), and adult
      respiratory distress syndrome (ARDS). DESIGN: Prospective, observational study.
      SETTING: A university hospital intensive care unit and research laboratory.
      PATIENTS: Six patients with sepsis, six patients with septic shock, and six
      patients with ARDS. Eight healthy volunteers and eight ventilated but noninfected
      patients served as controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:
      Morphologically passive and active neutrophil deformability as defined by the
      micropipette method was significantly decreased in patients with SP, SS, and ARDS
      associated with sepsis as compared with both control groups. Neutrophils from SS
      and ARDS patients were significantly more rigid as compared with neutrophils from
      SP patients but they did not differ from each other. The percentage of activated
      neutrophils was significantly higher in SP, SS, and ARDS patients. Increased
      passive neutrophil rigidity was significantly attenuated after coincubation with
      cytochalasin D. Tumor necrosis factor-alpha and interleukin-1beta serum levels
      were significantly higher in SP, SS, and ARDS patients. CONCLUSIONS: The entire
      neutrophil population is less deformable in SP, SS, and ARDS patients. The
      decreased deformability of passive neutrophils suggests that a direct mechanism
      involving actin polymerization, distinct from cell activation, is involved. These
      observations may be important in the mechanism of impaired vascular flow in
      patients with sepsis.

PMID- 10921565
TI  - Soluble selectins and the systemic inflammatory response syndrome after
      successful cardiopulmonary resuscitation.
AB  - OBJECTIVE: Elevated cytokine levels have been reported after ischemia/reperfusion
      injury and might cause a systemic inflammatory response syndrome (SIRS) after
      successful cardiopulmonary resuscitation (CPR). It is unknown whether patients
      with SIRS after CPR exhibit higher levels of soluble adhesion molecules than
      patients without SIRS and whether SIRS or elevation of adhesion molecules is
      associated with outcome after CPR. We analyzed the relationships among various
      CPR-related variables, plasma levels of E- and P-selectin, the occurrence of SIRS
      after CPR, and the development of sepsis and outcome. DESIGN: Prospective,
      controlled study. SETTING: Intensive care unit at a university hospital.
      PATIENTS: A total of 25 patients on the second day after successful CPR and 7 non
      critically ill control patients. INTERVENTIONS: Blood sampling for determination
      of plasma levels of soluble (s) E- and P-selectin. MEASUREMENTS AND MAIN RESULTS:
      SIRS was a frequent finding after CPR (66% of all patients) unrelated to time
      until return of spontaneous circulation (SIRS, 17+/-13 mins; no SIRS, 19+/-16
      mins; p = .761), epinephrine dose (SIRS, 4+/-5 mg; no SIRS, 5+/-6 mg; p = .906),
      or serum lactate level after CPR (SIRS, 8.6+/-2.6 mmol/L; no SIRS, 8.7+/-4.0
      mmol/L; p = .174). sP-selectin levels were higher in patients with SIRS (291.7+/
      227.4 ng/mL) compared with patients without SIRS (113.4+/-88.4 ng/mL; p = .018)
      or with non-critically ill patients (116.9+/-33.4 ng/mL; p = .031). Compared with
      non-critically ill control patients (42.8+/-19.4 ng/mL), sE-selectin levels were
      higher in patients with (96.2+/-47.3 ng/mL; p = .023) and without SIRS (99.5+/
      65.7 ng/mL; p = .030). sP-selectin was higher in patients developing sepsis
      within 1 wk after CPR (n = 9) than in patients without sepsis (350.2+/-233.4
      ng/mL vs. 158.5+/-157.8 ng/mL; p = .022) and sE-selectin levels were higher in
      nonsurvivors (n = 5) than in survivors (144.2+/-62.4 ng/mL vs. 85.7+/-45.3 ng/mL;
      p = .025) whereas SIRS was unrelated to the development of sepsis (p = .4) and
      unrelated to survival (p = .4). CONCLUSIONS: SIRS is an unspecific finding after
      CPR with only minor impact on outcome. Determination of sP- and sE-selectin early
      after CPR might help to identify patients at a high risk for sepsis or for an
      adverse outcome, respectively.

PMID- 10921566
TI  - Decreased serum insulin-like growth factor-I in burn patients: relationship with
      serum insulin-like growth factor binding protein-3 proteolysis and the influence
      of lipid composition in nutritional support.
AB  - OBJECTIVES: To test the effects of the amount and type of fat in the nutritional
      support on serum insulin-like growth factor (IGF)-I concentrations in burn
      patients and to test the hypothesis that the serum proteolytic activity for
      insulin-like growth factor binding protein (IGFBP)-3 is a major mechanism for the
      decreased serum IGF-I observed in these patients. DESIGN: Randomized, double
      blind trial of three different nutritional supports and analysis of serum IGF-I,
      IGFBP-3, and serum IGFBP-3 proteolysis. SETTING: Burn center in a university
      hospital. PATIENTS: A total of 23 severely burned (>25% total body surface area
      burned) adult patients. INTERVENTIONS: Patients were randomly assigned to three
      types of nutritional support differing in the amount of energy derived from fat
      and the presence or absence of fish oil: Group I (control), 35% fat; Group II,
      15% fat; Group III, 15% fat with 50% as fish oil. Nutritional support was both
      parenteral and enteral and was started within 24 hrs of admission. MEASUREMENTS
      AND MAIN RESULTS: Serum IGF-I and IGFBP-3 were measured by radioimmunoassay every
      3 days for 28 days in 23 severely burned adults. In six patients, IGFBP-3 was
      measured by ligand binding assay and the serum proteolytic activity for rhIGFBP-3
      was measured as well. Serum IGF-I concentration was low in all subjects
      throughout the study period, but did increase with time (p < .01); significantly
      higher values were found in Group III (p < .05). Multivariate analysis showed
      that fish oil and low fat solutions were significantly correlated to serum IGF-I
      concentrations. Serum IGFBP-3 (radioimmunoassay) was higher than normal
      throughout the study with no difference between the groups. Between days 4 and
      16, IGFBP-3 was cleaved into two fragments in all patients studied, and the
      molecular weights of the fragments were equal to those observed in the serum of a
      woman late in pregnancy. During this period of time, serum proteolytic activity
      for rhIGFBP-3 was >30% in 24 of the 30 samples measured, whereas 20 of the 28
      samples measured thereafter were normal (<25%). Serum IGFBP-3 concentration from
      ligand binding assay was correlated with serum proteolytic capacity in all
      subjects (mean r2 = 0.77; p < .01) and with serum IGF-I concentrations in five of
      six subjects (mean r2 = 0.81; p < .01). CONCLUSIONS: In burn injury, serum IGF-I
      concentrations are sensitive to the amount and type of fat in their nutritional
      support. The presence of fish oil allowed for a more rapid recovery of serum IGF
      I levels. The proteolysis of IGFBP-3 may be an important cause of the decreased
      serum IGF-I values and the protease(s) responsible for this seem to be similar to
      those observed in late pregnancy.

PMID- 10921567
TI  - Protein C substitution in sepsis-associated purpura fulminans.
AB  - OBJECTIVE: To assess the effect of protein C (PC) substitution on imminent
      peripheral necroses and overall outcome in patients with sepsis-associated
      purpura fulminans. DESIGN: Case series. SETTING: Intensive care units of two
      university hospitals. PATIENTS: A total of 12 patients with purpura fulminans,
      disseminated intravascular coagulation and imminent peripheral necroses in
      association with sepsis caused by Neisseria meningitidis (n = 5), Streptococcus
      pneumoniae (n = 2), Capnocytophaga canimorsus (n = 2), and Staphylococcus aureus
      (n = 1). In two patients, no pathogens were identified. INTERVENTIONS:
      Intravenous administration of PC concentrate (100 IU/kg every 6 hrs). In
      addition, antithrombin III substitution, antimicrobial therapy, hemodynamic
      support, and mechanical ventilation in all patients and hemodiafiltration in 10
      patients. MAIN RESULTS: After the onset of PC, progressive peripheral ischemia
      was reversed irrespective of the etiology of infection. Laboratory variables
      reflecting disseminated intravascular coagulation improved rapidly, although the
      recovery of the platelet count was retarded in the patients who subsequently
      died. No drug-related adverse events were noted. Amputations were necessary in
      two patients, and necrotic tips of fingers and toes were macerated in a third.
      The hospital mortality was 42%. Of the five lethal cases, two were caused by S.
      pneumoniae, one by N. meningitidis, one by C. canimorsus, and one by an unknown
      pathogen. CONCLUSIONS: This article provides encouraging results on the use of PC
      substitution in meningococcal purpura and presents new data on the administration
      of this drug to patients with septic purpura caused by other bacterial species.
      By clinical judgment, PC limited the extent of tissue necrosis. The small number
      of patients does not allow for any conclusions on the potential effect of PC on
      mortality. A controlled and randomized study with a larger number of patients is
      needed before any recommendations can be given on the use of PC in sepsis-related
      purpura fulminans and shock.

PMID- 10921569
TI  - Segmental bioelectrical impedance analysis to assess perioperative fluid changes.
AB  - OBJECTIVES: Perioperative fluid accumulation determination is a challenge for the
      clinician. Bioelectrical impedance analysis (BIA) is a noninvasive method based
      on the electrical properties of tissues, which can assess body fluid
      compartments. The study aimed at assessing their changes in three types of
      surgery (thoracic, abdominal, and intracranial) requiring various regimens of
      fluid administration. DESIGN: Prospective descriptive trial. PATIENTS: A total of
      26 patients scheduled for elective surgery were separated into three groups
      according to site of surgery: thoracic (n = 8), abdominal aortic (n = 8), and
      brain surgery (n = 10). SETTING: University teaching hospital. INTERVENTION:
      None. MEASUREMENTS: Whole body, segmental (arm, trunk, and legs) BIA at multiple
      frequency (0.5, 50, 100 kHz) was used to assess perioperative fluid accumulation
      after surgery. The fluid balances were calculated from the charts. RESULTS: The
      patients were aged 62+/-4 yrs. Fluid balances were 4.8+/-1.0 L, 4.1+/-0.5 L, and
      1.9+/-0.3 L, respectively, in the three groups. In trunk surgery patients, fluid
      accumulation was detected as a drop in impedance in the operated area at all
      frequencies. In the operated area, there was an expansion of both intra- and
      extracellular compartments. A reduction in high frequencies' impedance in the
      legs was only detected after aortic surgery. Fluid accumulation and trunk
      impedance changes were strongly correlated. Neurosurgery only induced minor body
      fluid changes. CONCLUSIONS: Segmental BIA is able to detect and localize
      perioperative fluid accumulation. It may become a bedside tool to quantify and to
      localize fluid accumulation.

PMID- 10921568
TI  - Multicenter study of whole-blood creatinine, total carbon dioxide content, and
      chemistry profiling for laboratory and point-of-care testing in critical care in
      the United States.
AB  - OBJECTIVES: To introduce a creatinine biosensor and a total carbon dioxide
      content (TCO2) method for whole-blood measurements, to evaluate the clinical
      performance of a new transportable analyzer that simultaneously performs these
      two and six other tests (Na+, K+, Cl-, glucose, urea nitrogen, and hematocrit),
      and to assess the potential of the new analyzer for point-of-care testing in
      critical care by comparing results obtained by nonlaboratory personnel and by
      medical technologists. DESIGN: Multicenter sites compared whole-blood
      measurements with the transportable analyzer to plasma measurements from the same
      specimens with local reference instruments. One site compared whole-blood results
      produced by nonlaboratory personnel vs. medical technologists and evaluated day
      to-day and within-day precision at the point of care. SETTINGS AND PATIENTS: Four
      medical centers in the United States. Venous and arterial specimens from 710
      critically ill patients with a variety of diagnoses. Point-of-care testing in the
      emergency room and operating room. RESULTS: The linear regression analyses at the
      four medical centers showed the following: creatinine (a) slope, 0.91 to 1.22,
      (b) y intercept, -0.07 to 0.15 mg/dL, and (c) r2, 0.77 to 1.00; and TCO2: (a)
      slope, 0.64 to 1.00, (b) y intercept, 1.36 to 9.6 mmol/L, and (c) r2, 0.52 to
      0.72 (yi, whole-blood analyses; xi, plasma reference measurements). Bland-Altman
      plots also were used to assess multicenter creatinine and TCO2 results. Of the
      other analytes, K+, glucose, and urea nitrogen had the highest r2-values. For the
      eight chemistry profile tests performed at the point of care (yi, nonlaboratory
      personnel results; xi, medical technologist results), the average value of r2 was
      0.96 (SD 0.08) in the operating room and 0.96 (SD 0.06) in the emergency room,
      and mean paired differences (yi - xi) were not statistically or clinically
      significant. Precision was acceptable. CONCLUSIONS: The performance of the
      creatinine biosensor and the TCO2 method was acceptable for whole-blood samples.
      Comparisons of whole-blood results from the transportable analyzer and plasma
      results from the local reference instruments revealed analyte biases that may be
      attributed to differences between direct whole-blood analyses and indirect
      diluted plasma measurements and other factors. Performance of nonlaboratory
      personnel and medical technologists was equivalent for point-of-care testing in
      critical care settings. The whole-blood analyzer should be useful when patient
      care demands immediate results.

PMID- 10921570
TI  - Effects of inhaled nitric oxide in a rat model of Pseudomonas aeruginosa
      pneumonia.
AB  - OBJECTIVE: Antimicrobial effects of nitric oxide (NO) have been demonstrated in
      vitro against a variety of infectious pathogens, yet in vivo evidence of a
      potential therapeutic role for exogenous NO as an antimicrobial agent is limited.
      Thus, we assessed the effects of inhaled NO on pulmonary infection, leukocyte
      infiltration, and NO synthase (NOS) activity in a rat model of Pseudomonas
      aeruginosa pneumonia. DESIGN: Controlled animal study. SETTING: Research
      laboratory of an academic institution. SUBJECTS: Male Sprague-Dawley rats.
      INTERVENTIONS: After intratracheal instillation of either P. aeruginosa or saline
      (sham), rats were randomly exposed to either 40 ppm of inhaled NO or room air
      (RA) for 24 hrs before they were killed. MEASUREMENTS AND MAIN RESULTS: Inhaled
      NO in pneumonia rats markedly reduced pulmonary bacterial load (0.02+/-0.01% vs.
      0.99+/-0.59% of bacterial input in pneumonia with room air, p < .05) and
      pulmonary myeloperoxidase activity, a marker of leukocyte infiltration (21.7+/
      3.8 vs. 55.0+/-8.1 units in pneumonia with room air, p < .05), but had no effect
      on systemic hemodynamics or gas exchange. Pneumonia was associated with enhanced
      pulmonary NOS activity (8.8+/-2.4 vs. 0.2+/-0.1 pmol citrulline/min/mg protein in
      sham, p < .01) and increased plasma levels of nitrites/nitrates (NOx-; 45+/-7 vs.
      16+/-3 micromol/L in sham, p < .01). Inhaled NO therapy attenuated the pneumonia
      induced increase in pulmonary calcium-independent NOS activity (p < .05) and
      markedly increased plasma NOx- levels. Exposure of P. aeruginosa in culture to 40
      ppm of ambient NO confirmed a delayed antibacterial effect of NO in vitro.
      CONCLUSIONS: Inhaled NO has an important antibacterial effect both in vitro and
      in vivo against P. aeruginosa and is associated with reduced pulmonary leukocyte
      infiltration in vivo. These results in a rat model of P. aeruginosa pneumonia
      suggest that future studies should address the possible clinical effects of
      inhaled NO therapy in pneumonia.

PMID- 10921571
TI  - Alteration in diaphragmatic contractility during septic peritonitis in rats:
      effect of polyethylene glycol-absorbed superoxide dismutase.
AB  - OBJECTIVES: To assess the alterations in diaphragmatic contractility measured in
      vitro during experimental septic peritonitis and to evaluate the effect of
      polyethylene glycol-absorbed superoxide dismutase (PEG-SOD) on the alterations in
      contractility. DESIGN: Prospective, randomized, controlled animal trial. SETTING:
      Research laboratory. SUBJECTS: A total of 321 male Wistar rats, weighing 250-300
      g. INTERVENTIONS: Rats were treated with cecal ligation and puncture (CLP). In
      the first experiment, diaphragmatic contractility was measured at 4, 10, 12, and
      16 hrs after CLP. In the second experiment, PEG-SOD (4,000 units/kg) was
      administered intraperitoneally, and then diaphragmatic contractility was measured
      at 10 and 16 hrs after CLP. Levels of lipid peroxides and antioxidant enzymes in
      the diaphragm tissue were measured at 10 and 16 hrs after CLP. MEASUREMENTS AND
      MAIN RESULTS: In experiment 1, diaphragmatic twitch characteristics and force
      frequency relationships were determined at 4, 10, 12, and 16 hrs after CLP. In
      experiment 2, the effects of administration of PEG-SOD on twitch characteristics
      and force-frequency relationships were determined at 10 and 16 hrs after CLP. The
      levels of diaphragmatic thiobarbituric acid reactive substances and superoxide
      dismutase (SOD) and glutathione peroxidase activities were measured at 10 and 16
      hrs after CLP. Twitch tension and force-frequency curves were significantly lower
      in the CLP groups than in the sham-operated group. Administration of PEG-SOD
      attenuated the reduction in twitch tension and the downward shift of force
      frequency curves after CLP. Diaphragmatic levels of thiobarbituric acid reactive
      substances increased after CLP. However, the administration of PEG-SOD prevented
      increases in levels of diaphragmatic thiobarbituric acid reactive substances
      after CLP. Diaphragmatic SOD activity, but not glutathione peroxidase activity,
      was increased after CLP. CONCLUSIONS: Intra-abdominal sepsis (CLP) induced a
      marked reduction in diaphragmatic contractility, but PEG-SOD attenuated this
      reduction. Therefore, we conclude that oxygen-derived free radicals play an
      important role in the alterations in diaphragmatic contractility during intra
      abdominal sepsis.

PMID- 10921572
TI  - End-tidal carbon dioxide as a noninvasive indicator of cardiac index during
      circulatory shock.
AB  - OBJECTIVE: To document the relationships between cardiac index and end-tidal
      carbon dioxide tension (PetCO2 during diverse low-flow states of circulatory
      shock. DESIGN: Randomized, prospective, controlled studies on animal models of
      hemorrhagic, septic, and cardiogenic shock. SETTING: University-affiliated
      research laboratory. SUBJECTS: Sixteen anesthetized domestic pigs weighing 35-45
      kg. INTERVENTIONS: Hemorrhagic shock was induced in five pigs by bleeding
      followed by reinfusion of shed blood. Septic shock was induced in five pigs by
      infusion of live Escherichia coli. Cardiogenic shock followed an interval of
      global myocardial ischemia after inducing and reversing ventricular fibrillation
      in six pigs. MEASUREMENTS AND MAIN RESULTS: PetCO2 was continuously measured.
      Cardiac index was measured intermittently by using conventional thermodilution
      techniques. Cardiac index was correlated with PetCO2 by polynomial regression and
      Bland-Altman analyses. PetCO2 was highly correlated with cardiac index during
      hemorrhagic shock (r2 = .69, p < .01), septic shock (r2 = .65, p < .01), and
      cardiogenic shock (r2 = .81, p < .01). PetCO2 predicted thermodilution cardiac
      index with bias of -11+/-27 (+/-2 SD) mL/min/kg during hemorrhagic shock, 1.3+/
      20.4 (+/- 2 SD) mL/min/kg during septic shock, and -1+/-12 (+/-2 SD) mL/min/kg
      during cardiogenic shock. CONCLUSIONS: Cardiac output and PetCO2 were highly
      related in diverse experimental models of circulatory shock in which cardiac
      output was reduced by >40% of baseline values. Therefore, measurement of PetCO2
      is a noninvasive alternative for continuous assessment of cardiac output during
      low-flow circulatory shock states of diverse causes.

PMID- 10921573
TI  - Combined therapy with zaprinast and inhaled nitric oxide abolishes hypoxic
      pulmonary hypertension.
AB  - OBJECTIVE: To determine whether the combination of the phosphodiesterase 5
      inhibitor zaprinast and inhaled nitric oxide (NO) decreases hypoxic pulmonary
      hypertension in the rat. DESIGN: Prospective, experimental study. SETTING: Animal
      laboratory of a university medical center. SUBJECTS: Male Sprague-Dawley rats.
      INTERVENTIONS: Anesthetized rats were mechanically ventilated and instrumented
      for measurement of mean systemic arterial pressure, pulmonary arterial pressure,
      and cardiac output. In group 1, four acute hypoxic challenges (FIO2 = 0.17 for 5
      mins) were performed: initial, during 40 ppm inhaled NO, immediately after
      discontinuation of 5 mins of inhaled NO, and final. In group 2 rats, an initial
      hypoxic challenge was performed and rats then received zaprinast (3 mg/kg bolus
      followed by 0.3 mg/kg/min infusion). Four hypoxic challenges analogous to group 1
      were then performed during zaprinast administration. MEASUREMENTS AND MAIN
      RESULTS: Initial hypoxic challenge produced similar increases in pulmonary
      arterial pressure in both groups. In group 1, inhaled NO either only before or
      only during hypoxia decreased the pulmonary hypertensive response to hypoxia. In
      group 2, zaprinast administration did not alter hemodynamics. Zaprinast alone
      decreased the pulmonary hypertensive response to hypoxia. The combination of
      zaprinast and inhaled NO (either before or during hypoxia) abolished the
      pulmonary hypertensive response to hypoxia. CONCLUSIONS: Treatment with inhaled
      NO for 5 mins before but not during hypoxia is as effective as inhaled NO during
      hypoxia. Inhaled NO and zaprinast both decrease the pulmonary hypertensive
      response to hypoxia, and the combination abolishes the response. The combination
      of a phosphodiesterase 5 inhibitor and inhaled NO may have clinical applicability
      in the treatment of pulmonary hypertension.

PMID- 10921574
TI  - Gut gavage with antiendotoxin antibodies reduces the liberation of tumor necrosis
      factor-alpha after hemorrhage/resuscitation.
AB  - OBJECTIVE: To evaluate the effect of gut gavage both alone and with enteral
      administration of monoclonal antibodies to endotoxin on the liberation of tumor
      necrosis factor (TNF)-alpha and subsequent hemodynamics after
      hemorrhage/resuscitation. DESIGN: Dose response intervention, sham-controlled
      animal study. SETTING: Research laboratory at a university medical center.
      ANIMALS: Instrumented rats (250-325 g body weight) underwent standardized
      hemorrhage/resuscitation. INTERVENTIONS: Animal groups received 4 hrs before
      hemorrhage/resuscitation: gastric gavage with Colyte alone (group 1), combined
      with E5 antiendotoxin at either 0.2 mg/100 g (group 2) or 2 mg/100 g body weight
      (group 3), or sham controls (group 4). There were six animals studied in each of
      the four groups. MEASUREMENTS AND MAIN RESULTS: For animals receiving gut gavage
      and high-dose E5 antiendotoxin, plasma concentrations of TNF-alpha (pg/mL) at 120
      mins after hemorrhage/resuscitation were significantly lower compared with sham
      controls (16+/-4 group 3; 65+/-36 group 4; mean +/- SD, p < .05). At 300 mins,
      this same treatment group had a significantly higher mean blood pressure (mm Hg)
      (110+/-6 group 3; 86+/-7 group 4: p < .05). Also at 300 mins after
      hemorrhage/resuscitation, plasma lactate concentrations (mmol/L) were
      significantly lower for all gut gavage treatment groups compared with sham
      control animals (1.9+/-0.2 group 1; 2.0+/-0.2 group 2; 1.8+/-0.2 group 3; 4.8+/
      2.8 group 4, p < .05). CONCLUSIONS: Prior treatment with gut gavage and enterally
      administered antiendotoxin antibodies reduces TNF-alpha liberation after
      hemorrhage/resuscitation and confers a subsequent improvement in hemodynamics and
      decreased plasma lactate concentrations. Such therapy may be efficacious in
      patients undergoing elective procedures where major hemorrhage is likely or in
      severely injured patients with continued or recurrent hemorrhage.

PMID- 10921575
TI  - Changes in cerebral venous prostanoids during midazolam-induced cerebrovascular
      hypotension in newborn piglets.
AB  - OBJECTIVES: We hypothesized that the effects of midazolam are associated with
      altered prostanoid synthesis in the newborn piglet during continuous infusion. To
      test this hypothesis, we examined the effect of midazolam on prostanoid
      production in the carotid artery and sagittal sinus vein before and during
      midazolam infusion. DESIGN: Prospective, randomized, controlled, experimental
      study. SETTING: Research laboratory at Long Beach Memorial Medical Center.
      SUBJECTS: Fourteen newborn piglets (1-3 days old, 1-1.5 kg) randomly assigned to
      receive either midazolam or vehicle (5% dextrose) infusion for 6 hrs.
      INTERVENTIONS: Two groups of animals received either a) a loading dose of 300
      microg/kg of midazolam over 15 mins, followed by a continuous intravenous
      infusion of 100 microg/kg/hr (n = 6), or b) equivalent volume bolus and
      intravenous infusions of 5% dextrose (control, n = 8). MEASUREMENTS AND MAIN
      RESULTS: Changes in systemic and cerebral venous hemodynamics, blood gases, and
      prostanoid (prostaglandin E2, 6-ketoprostaglandin F1 alpha, thromboxane B2)
      production were measured at baseline, postbolus, and at 0.5, 2, 4, and 6 hrs.
      Systemic and cerebral venous midazolam concentrations were measured at 0.5, 1, 2,
      3, 4, 5, and 6 hrs. Midazolam infusion did not affect systemic hemodynamics or
      blood gases. In contrast, midazolam infusion significantly reduced sagittal sinus
      vein blood pressure, PO2, oxygen saturation, and oxygen content. Cerebral
      fractional oxygen extraction increased and was positively correlated with
      cerebral fractional midazolam extraction. Concurrently, systemic and sagittal
      sinus vein plasma prostaglandin E2 concentrations decreased, whereas 6
      ketoprostaglandin F1 alpha concentrations increased with midazolam infusion.
      Thromboxane B2 concentrations increased transiently in the systemic plasma.
      CONCLUSIONS: Midazolam infusion preceded by a high bolus dose in newborn piglets
      alters systemic and sagittal sinus vein prostanoid production. It is also
      associated with changes in sagittal sinus vein blood pressure and cerebral
      fractional oxygen extraction. These changes may reflect decreased brain perfusion
      and metabolism during midazolam infusion.

PMID- 10921576
TI  - Role of macrophage inflammatory protein-2 in aspiration-induced lung injury.
AB  - OBJECTIVE: To determine the role of the chemokine, macrophage inflammatory
      protein (MIP)-2, in the pathogenesis of aspiration-induced lung injury in the
      rat. DESIGN: Prospective, randomized, controlled animal study. SETTING:
      University research laboratories. SUBJECTS: Adult, male Long-Evans rats.
      INTERVENTIONS: Anesthetized rats underwent induction of lung injury by well
      described models of aspiration triggered by intra-tracheal delivery of acid
      alone, gastric particles alone, or the combination. After injury, induction of
      MIP-2 messenger RNA in whole lungs and immunoreactive MIP-2 in bronchoalveolar
      lavage (BAL) fluids was determined. The contribution of MIP-2 to BAL fluid
      chemotactic activity was defined by using an in vitro chemotaxis assay. The in
      vivo effect of blocking MIP-2 on pulmonary vascular leak, BAL fluid neutrophils,
      PaO2/FIO2 ratio, and alveolar-arterial oxygen tension gradient in acid-induced
      lung injury was determined. MEASUREMENTS AND MAIN RESULTS: Induction of MIP-2
      messenger RNA and protein over time was observed in response to all three
      stimuli. A significant portion (25% to 41%) of the chemotactic activity in BAL
      fluids from injured rats was inhibited by anti-MIP-2 antibody. After acid injury,
      blocking of MIP-2 was associated with a 53% decrease in BAL fluid neutrophils and
      a 33% decrease in pulmonary vascular leak. Although acid injury both impaired
      oxygenation and increased venous admixture, in vivo blocking of MIP-2 was
      associated with improved oxygenation as well as decreased venous admixture.
      CONCLUSIONS: MIP-2 was up-regulated during the development of aspiration-induced
      lung injury in rats. MIP-2 contributed to lung accumulation of neutrophils via a
      chemotactic mechanism. Although oxygenation and venous admixture are worsened by
      acid-induced lung injury in vivo, blocking of MIP-2 at the onset of injury
      improved these physiologic alterations. Because the aspiration event often is
      witnessed, chemokines may be valid therapeutic targets for inhibiting the
      subsequent inflammatory response.

PMID- 10921577
TI  - Stimulation of pulmonary big endothelin-1 and endothelin-1 by antithrombin III: a
      rationale for combined application of antithrombin III and endothelin antagonists
      in sepsis-related acute respiratory distress syndrome?
AB  - OBJECTIVES: Antithrombin (AT) III reduces lung damage in animal models of septic
      acute respiratory distress syndrome (ARDS), which is generally attributed to
      stimulation of endothelial prostacyclin synthesis. However, clinical studies have
      failed so far to demonstrate mortality reduction by application of AT III. We
      investigated whether AT III stimulates pulmonary prostacyclin release. In
      addition, we hypothesized that it may promote pulmonary endothelins, thereby
      mitigating its own protective effect in the course of ARDS. DESIGN: Controlled
      experiment using isolated organs. SETTING: Experimental laboratory. SUBJECTS:
      Male Wistar rats. INTERVENTIONS: Isolated lungs were perfused over 120 mins in
      recirculatory mode in the presence of 50 microg/mL endotoxin (n = 11), 2U/mL AT
      III (n = 10), 5 U/mL AT III (n = 13), endotoxin plus 2 U/mL AT III (n = 5), or
      vehicle alone (controls, n = 13), respectively. MEASUREMENTS AND MAIN RESULTS: We
      determined the effects of AT III on vascular release of thromboxane B2, 6-keto
      prostaglandin-F1alpha, big endothelin-1, and endothelin-1. Control lungs released
      59+/-23 pg/mL thromboxane B2, 1,480+/-364 pg/mL 6-keto-prostaglandin-F1alpha,
      15.2+/-4.5 pg/mL big endothelin-1, and 0.46+/-0.13 pg/mL endothelin-1. Exposure
      to endotoxin increased thromboxane B2 release 2.9-fold, 6-keto-prostaglandin
      F1alpha release 1.6-fold, and endothelin-1 1.6-fold (p < .05 each); levels of big
      endothelin-1 were unchanged. AT III at 2 U/mL elevated production of big
      endothelin-1 (1.7-fold) and endothelin-1 (1.2-fold) (p < .05 for both). AT III at
      5 U/mL enhanced levels of big endothelin-1 (1.6-fold) and endothelin-1 (1.3-fold)
      (p < .05 for both). Neither dose of AT III affected thromboxane B2 or 6-keto
      prostaglandin-F1alpha concentrations. Application of 2 U/mL AT III plus endotoxin
      stimulated big endothelin-1 production (2.6-fold) compared with endotoxin or AT
      III alone (p < .05 for both), but did not further elevate endothelin-1 release.
      CONCLUSIONS: AT III does not stimulate pulmonary prostacyclin, but promotes
      pulmonary release of big endothelin-1 and endothelin-1 under basal and,
      particularly, under septic conditions, which may blunt the AT III-induced lung
      protection during ARDS. Therefore, we suggest combined application of AT III and
      endothelin antagonists in animal models of septic ARDS.

PMID- 10921578
TI  - High-frequency oscillatory ventilation and partial liquid ventilation after acute
      lung injury in premature lambs with respiratory distress syndrome.
AB  - OBJECTIVE: Conventional mechanical ventilatory support (CV) contributes to lung
      injury in premature lambs with respiratory distress syndrome, a disease that is
      characterized by progressive deterioration of gas exchange and increased lung
      inflammation. Lung recruitment strategies, such as high-frequency oscillatory
      ventilation (HFOV) and partial liquid ventilation (PLV), improve gas exchange and
      attenuate lung inflammation when instituted immediately after birth. However,
      whether these recruitment strategies are effective as rescue treatment after
      established lung injury is unknown. To determine the separate and combined
      effects of HFOV and PLV when initiated after the establishment of acute lung
      injury in severe respiratory distress syndrome, we studied the effects of these
      strategies on gas exchange and histologic signs of acute lung injury in premature
      lambs. DESIGN: Animals were intubated, treated with surfactant and ventilated
      with 1.00 FIO2 for 4 hrs. After 2 hrs, animals were either continued on CV
      (controls) or treated with one of three strategies: HFOV; CV + PLV; or HFOV +
      PLV. The response to low-dose inhaled nitric oxide (5 ppm) was measured in each
      group at the end of the study. SETTING: An animal laboratory affiliated with
      University of Colorado School of Medicine. SUBJECTS: A total of 20 premature
      lambs at 115-118 days of gestation (term = 147 days). MEASUREMENTS AND MAIN
      RESULTS: In comparison with control animals, each of the rescue therapies
      improved PaO2 after 1 hr of treatment. The HFOV and HFOV + PLV groups had higher
      PaO2 than CV + PLV or CV alone (p < .05). Mean airway pressure (Paw) was lower in
      the PLV groups during CV or HFOV compared with their controls (p < .05). Inhaled
      NO improved PaO2 in all groups; however, the increase in PaO2 was greatest in the
      HFOV + PLV group (p < .05). Histologic examination and myeloperoxidase assay were
      not different between groups. CONCLUSION: We conclude that each lung recruitment
      strategy improved oxygenation in premature lambs with established lung injury.

PMID- 10921579
TI  - Biologically variable ventilation increases arterial oxygenation over that seen
      with positive end-expiratory pressure alone in a porcine model of acute
      respiratory distress syndrome.
AB  - OBJECTIVES: We compared biologically variable ventilation (BVV) (as previously
      described) (1) with conventional control mode ventilation (CV) in a model of
      acute respiratory distress syndrome (ARDS) both at 10 cm H2O positive end
      expiratory pressure. DESIGN: Randomized, controlled, prospective study. SETTING:
      University research laboratory. SUBJECTS: Farm-raised 3- to 4-month-old swine.
      INTERVENTIONS: Oleic acid (OA) was infused at 0.2 mL/kg/hr with FIO2 = 0.5 and 5
      cm H2O positive end-expiratory pressure until PaO2 was < or =60 mm Hg; then all
      animals were placed on an additional 5 cm H2O positive end-expiratory pressure
      for the next 4 hrs. Animals were assigned randomly to continue CV (n = 9) or to
      have CV computer controlled to deliver BVV (variable respiratory rate and tidal
      volume; n = 8). Hemodynamic, expired gas, airway pressure, and volume data were
      obtained at baseline (before OA), immediately after OA, and then at 60-min
      intervals for 4 hrs. MEASUREMENTS AND MAIN RESULTS: At 4 hrs after OA injury,
      significantly higher PaO2 (213+/-17 vs. 123+/-47 mm Hg; mean+/-SD), lower shunt
      fraction (6%+/-1% vs. 18%+/-14%), and lower PaCO2 (50+/-8 vs. 65+/-11 mm Hg) were
      seen with BVV than with CV. Respiratory system compliance was greater by
      experiment completion with BVV (0.37+/-0.05 vs. 0.31+/-0.08 mL/cm H2O/kg). The
      improvements in oxygenation, CO2 elimination, and respiratory mechanics occurred
      without a significant increase in either mean airway pressure (14.3+/-0.9 vs.
      14.9+/-1.1 cm H2O) or mean peak airway pressure (39.3+/-3.5 vs. 44.5+/-7.2 cm
      H2O) with BVV. The oxygen index increased five-fold with OA injury and decreased
      to significantly lower levels over time with BVV. CONCLUSIONS: In this model of
      ARDS, BVV with 10 cm H2O positive end-expiratory pressure improved arterial
      oxygenation over and above that seen with CV with positive end-expiratory
      pressure alone. Proposed mechanisms for BVV efficacy are discussed.

PMID- 10921580
TI  - Mild or moderate hypothermia, but not increased oxygen breathing, increases long
      term survival after uncontrolled hemorrhagic shock in rats.
AB  - OBJECTIVE: To test the hypotheses that, for uncontrolled hemorrhagic shock (UHS)
      in rats, mild hypothermia, compared with normothermia, would increase long-term
      survival as well as moderate hypothermia, oxygen breathing would increase
      survival further, and hypothermia and oxygen would mitigate visceral ischemia
      (dysoxia) during UHS. DESIGN: Prospective, randomized study. SETTING: Animal
      research laboratory. SUBJECTS: A total of 54 male Sprague-Dawley rats.
      INTERVENTIONS: Under light anesthesia and spontaneous breathing, rats underwent
      UHS phase I of 75 mins, with initial withdrawal of 3 mL/100 g of blood over 15
      mins, followed by UHS via tail amputation and limited fluid resuscitation to
      maintain mean arterial pressure at > or =40 mm Hg; resuscitation phase II of 60
      mins (from 75 mins to 135 mins) with hemostasis and aggressive fluid
      resuscitation to normalize hemodynamics; and observation phase III to 72 hrs.
      Rats were randomly divided into nine groups (n = 6 each) with three rectal
      temperature levels (38 degrees C [normothermia] vs. 34 degrees C [mild
      hypothermia] vs. 30 degrees C [moderate hypothermia]) by surface cooling; each
      with 3 FIO2 levels (0.25 vs. 0.5 vs. 1.0). MEASUREMENTS AND MAIN RESULTS:
      Hypothermia increased blood pressure compared with normothermia. Increased FIO2
      had no effect on blood pressure. Additional blood loss from the tail cut was
      small, with no differences among groups. Hypothermia and FIO2 of 0.5 decreased
      visceral hypoxia, as measured by the difference between visceral (liver and
      jejunum) surface Pco2 and PaCO2 during UHS. Compared with normothermia, mild
      hypothermia increased the survival time and rate as well as moderate hypothermia
      (p < .01 by life table), without a significant difference between mild and
      moderate hypothermia. Increased FIO2 had no effect on survival time or rate.
      CONCLUSIONS: After severe UHS and resuscitation in rats, mild hypothermia during
      UHS, compared with normothermia, increases blood pressure, survival time and 72
      hr survival rate as well as moderate hypothermia. Mild hypothermia is clinically
      more feasible and safer than moderate hypothermia. Increased FIO2 seems to have
      no significant effect on outcome.

PMID- 10921581
TI  - Lidocaine attenuates sepsis-induced diaphragmatic dysfunction in hamsters.
AB  - OBJECTIVES: Sepsis or endotoxemia causes diaphragmatic dysfunction, which may
      contribute to respiratory distress. Toxic free radicals are partly responsible
      for the pathogenesis. Lidocaine scavenges the reactive molecules. The purpose of
      the current study was to examine whether lidocaine prevents the diaphragmatic
      dysfunction of sepsis. DESIGN: Prospective, randomized animal study. SETTING:
      University research laboratory. SUBJECTS: A total of 40 male Golden-Syrian
      hamsters. INTERVENTIONS: The animals were randomly allocated to one of five
      groups (n = 8 each): hamsters undergoing sham laparotomy alone and receiving
      saline infusion (Sham group), those undergoing cecal ligation with puncture (CLP)
      and receiving an infusion of saline (Sepsis group), those undergoing sham
      laparotomy and receiving infusion of lidocaine, 2 mg/kg/hr (Sham-LID group),
      those undergoing CLP and receiving infusion of lidocaine, 1 mg/kg/hr (Sepsis-LID
      1 group), and those undergoing CLP and receiving infusion of lidocaine, 2
      mg/kg/hr (Sepsis-LID 2 group). Subcutaneous infusion of saline or lidocaine was
      started 6 hrs before surgery and continued until 24 hrs after the operation when
      all hamsters were killed. MEASUREMENTS AND MAIN RESULTS: Diaphragmatic
      contractility and fatigability were assessed in vitro by using muscle strips
      excised from the costal diaphragms. Diaphragmatic levels of malondialdehyde
      (MDA), an index of free radicals-mediated lipid peroxidation, were also measured.
      Twitch and tetanic tensions in the Sepsis group were reduced compared with the
      Sham group. Tensions generated during fatigue trials were decreased, and MDA
      levels were elevated in diaphragms from the Sepsis group. An infusion of 2
      mg/kg/hr lidocaine attenuated contractile dysfunction, aggravation of
      fatigability, and the increase in MDA formation. In contrast, 1 mg/kg/hr
      lidocaine failed to do so. Electrophysiologic diaphragmatic characteristics in
      the Sham-LID group were similar to those in the Sham group. CONCLUSIONS:
      Pretreatment with 2 mg/kg/hr but not 1 mg/kg/hr lidocaine attenuated sepsis
      induced diaphragmatic dysfunction in hamsters assessed by contractile profiles
      and endurance capacity. This beneficial effect of lidocaine may be attributable,
      in part, to inhibition of lipid peroxidation in the diaphragm.

PMID- 10921582
TI  - Intratracheal pulmonary ventilation in a rabbit lung injury model: continuous
      airway pressure monitoring and gas exchange efficacy.
AB  - OBJECTIVES: To compare carinal pressures vs. proximal airway pressures, and gas
      exchange efficacy with a constant minute volume, in lung-injured rabbits during
      conventional mechanical ventilation (CMV) and intratracheal pulmonary ventilation
      (ITPV); and to evaluate performance of a prototype ITPV gas delivery and
      continuous airway pressure monitoring system. DESIGN: Prospective controlled
      study. SETTING: Animal research laboratory at a teaching hospital. SUBJECTS:
      Sixteen adult female rabbits. INTERVENTIONS: Anesthetized rabbits were
      tracheostomized with a multilumen endotracheal tube. Anesthesia and muscle
      relaxation were maintained continuously throughout the study. Proximal airway
      pressures and carinal pressures were recorded continuously. The injection port of
      the multilumen endotracheal tube was used for the carinal pressure monitoring. To
      prevent obstruction of the port, it was flushed with oxygen at a rate of 11
      mL/min. CMV was initiated with a pressure-limited, time-cycled ventilator set at
      an FiO2 of 1.0 and at a flow of 1.0 L/kg/min. The pressure limit of the
      ventilator was effectively disabled. A normal baseline for arterial blood gases
      was achieved by adjusting the inspiratory/expiratory time ratios. ITPV was
      established using a flow of 1.0 L/kg/min through a reverse thrust catheter, at
      the same baseline and inspiratory/expiratory ratio. Carinal positive end
      expiratory pressure was maintained at a constant value of 2 cm H2O by adjusting
      the expiratory resistance of the ventilator circuit Lung injury was achieved over
      a 30-min period by three normal saline lavages of 5 mL/kg each. After lung
      injury, all animals were consecutively ventilated for 1 hr with CMV, for 1 hr
      with ITPV, and again for 1 hr with CMV. Six rabbits were ventilated at 30
      breaths/min (group 1), and ten rabbits were ventilated at 80 breaths/min (group
      2). Four rabbits in group 2 were subjected, 1 hr after return to CMV from ITPV,
      to another session of ITPV, with positive end-expiratory pressure gradually being
      increased to 4, 6, and 8 cm H2O for 15 mins each. RESULTS: No significant
      differences were observed in carinal peak inspiratory pressure between CMV and
      ITPV modes, at both low and high frequencies of breathing, indicating that the
      inspired tidal volume remained constant during both modes of ventilation.
      Significant gradients were noted between proximal airway and carinal peak
      inspiratory pressure during ITPV but not during CMV. Initiation of ITPV, at a
      flow of 1.0 L/kg/min, required an increase in the ventilator expiratory
      resistance to maintain a constant level of positive end-expiratory pressure (2 cm
      H2O) as measured at the carina. During ITPV, the PaCO2 was significantly reduced
      by 20% at 30 breaths/min (p < .05) and by 22% at 90 breaths/min (p < .01),
      compared with CMV. Arterial oxygenation was significantly enhanced with a
      positive end-expiratory pressure of 6 and 8 cm H2O (p < .05 and .001,
      respectively), compared with a positive end-expiratory pressure of 2 cm H2O
      during ITPV. All components of the new prototype gas delivery and airway pressure
      monitoring system functioned without failure, at least for 3 hrs of the CMV,
      ITPV, and CMV trials. CONCLUSIONS: ITPV in saline-lavaged, lung-injured rabbits
      at breathing frequencies of 30 and 80 breaths/min, compared with CMV at the same
      minute ventilation, can improve CO2 exchange. During ITPV, significant pressure
      gradients can develop between carinal and proximal airway pressures. Continuous
      carinal pressure monitoring is therefore necessary for the safe clinical
      application of ITPV. Reliable carinal pressure monitoring can be achieved by
      adding a small bias flow through the carinal pressure monitoring port. Although
      ITPV can remove CO2 from injured lungs efficiently, simultaneous addition of
      positive end-expiratory pressure can further improve arterial oxygenation.

PMID- 10921583
TI  - Antioxidant enzymes are induced during recovery from acute lung injury.
AB  - OBJECTIVE: To determine the contribution of the pulmonary antioxidant defense
      enzymes of the hexose monophosphate (HMP) shunt and glutathione systems to
      recovery from oxidant-mediated lung injury in an animal model shown to closely
      resemble the clinical syndrome of acute respiratory distress syndrome. DESIGN:
      Prospective, controlled laboratory study on phorbol myristate acetate (PMA)
      induced lung injury in rabbits. SETTING: Animal research laboratory. SUBJECTS:
      Rabbits were injected with PMA (80 microg/kg) for 3 consecutive days. Control
      animals received normal saline. MEASUREMENTS AND MAIN RESULTS: Lungs were
      harvested at 24, 48, 72, and 96 hrs (n = 5/time point) after PMA injection or
      after the third injection of normal saline in control animals (n = 6). The
      cytosolic fraction from lung and bronchial alveolar lavage (BAL) fluid was used
      for measurements of HMP shunt and glutathione enzymes. Pulmonary activity peaked
      at 48 hrs post-PMA injury with a 40% increase in glucose-6-phosphate
      dehydrogenase activity and a 32% increase in 6-phosphogluconate dehydrogenase
      activity over control levels. BAL activity was maximal at 72 hrs with an increase
      of 98% in glucose-6-phosphate dehydrogenase and 346% in 6-phosphogluconate
      dehydrogenase activities. Glutathione peroxidase was maximally induced by 77% at
      48 hrs in BAL and by 107% at 24 hrs in lung. Glutathione reductase activity did
      not increase significantly in either lung or BAL. CONCLUSIONS: The observed
      induction of the antioxidant enzymes in response to PMA suggests that both the
      HMP shunt and the glutathione systems contribute to the recovery phase of oxidant
      mediated lung injury. The inability of natural host defenses to regenerate
      reduced glutathione may explain failure of recovery from acute respiratory
      distress syndrome and suggests an avenue for clinical intervention.

PMID- 10921584
TI  - Effects of propofol, etomidate, and pentobarbital on critical oxygen delivery.
AB  - OBJECTIVE: To test the hypothesis that propofol, etomidate, and pentobarbital
      increase critical oxygen delivery in a dose-dependent manner during progressive
      hemorrhage. DESIGN: Prospective, randomized laboratory investigation. SETTING:
      University laboratory. SUBJECTS: A total of 40 anesthetized, paralyzed, and
      mechanically ventilated dogs weighing 29.2+/-4.6 kg. INTERVENTIONS: Dogs were
      randomly assigned to be anesthetized with propofol (n = 13), etomidate (n = 13),
      or pentobarbital (n = 14) at either low or high dosages. At 30 mins after
      splenectomy, the dogs underwent progressive hemorrhage by successive withdrawals
      of 3-5 mL/kg arterial blood. MEASUREMENTS AND MAIN RESULTS: At each step of
      hemorrhage, oxygen consumption and oxygen delivery were determined. Oxygen
      consumption was obtained from expired gas analysis, and oxygen delivery was
      determined from thermodilution cardiac output and calculated arterial oxygen
      content. In each animal, critical oxygen delivery and critical oxygen consumption
      were obtained from a plot of oxygen consumption vs. oxygen delivery as the point
      of intersection of the two best-fit regression lines determined by a least sum of
      squares method. Critical oxygen extraction was obtained by dividing critical
      oxygen consumption by critical oxygen delivery. In the three groups, animals
      receiving the higher anesthetic infusion had a significantly higher critical
      oxygen delivery (propofol: 10.5+/-0.8 vs. 13.9+/-2.5 mL/min/m2, p < .05;
      etomidate: 10.1+/-0.7 vs. 13.4+/-3.0 mL/min/m2, p < .05; pentobarbital: 7.8+/-1.0
      vs. 12.3+/-2.5 mL/min/m2, p < .01) attributable to a lower critical oxygen
      extraction ratio (propofol: 41.1+/-6.4% vs. 54.2+/-2.5%, p < .01; etomidate:
      42.7+/-10.2% vs. 60.6+/-7.1%, p < .01; pentobarbital: 42.2+/-7.2% vs. 64.3+/
      8.8%, p < .01). CONCLUSIONS: This study indicates that propofol, etomidate, and
      pentobarbital increased critical oxygen delivery in a dose-dependent manner. This
      effect was mainly related to a decrease in tissue oxygen extraction capabilities.

PMID- 10921585
TI  - Effects of norepinephrine on the distribution of intestinal blood flow and tissue
      adenosine triphosphate content in endotoxic shock.
AB  - OBJECTIVE: To investigate, during endotoxic shock, the effect of a treatment of
      norepinephrine (NE) administration on the distribution of blood flow and
      adenosine triphosphate (ATP) content in the intestinal wall. DESIGN: Randomized
      controlled trial. SETTING: Animal laboratory. SUBJECTS: Domestic pigs.
      INTERVENTION: A total of 18 pigs were anesthetized with ketamine and
      pentobarbital, mechanically ventilated, hemodynamically monitored, and then
      challenged with a continuous infusion of Escherichia coli endotoxin (ET) (15
      microg/kg) for 2 hrs. Three groups of six animals were studied; one served as
      time control, one group received ET and fluid resuscitation, and a third group
      received ET, fluid resuscitation, and a perfusion of NE to maintain constant mean
      arterial pressure (MAP). MEASUREMENTS AND MAIN RESULTS: Cardiac output,
      mesenteric arterial blood flow, MAP, pulmonary pressure, and portal pressure were
      measured. Intestinal mucosal intracellular pH (pHi) was determined with saline
      filled balloon tonometers. Tissue blood flows to the intestinal mucosa and to the
      muscular layer were independently measured with fluorescent microspheres, using
      the arterial reference sample method. Measurements were performed before and 3
      hrs after the start of the ET challenge. At the end of the experiments,
      muscularis and mucosal samples were quickly frozen for further enzymatic ATP
      measurements. ET administration with fluid resuscitation induced a distributive
      shock with increased mucosal blood flow and decreased muscularis blood flow,
      whereas pHi decreased and mucosal ATP content was significantly lower than in the
      control group. In the group receiving ET plus NE, MAP remained constant, mucosal
      blood flow did not increase, and mucosal ATP content was equal to the time
      control group. Meanwhile, mucosal acidosis was not prevented. CONCLUSIONS:
      Normodynamic endotoxic shock may induce an alteration in mucosal oxygenation,
      despite an increased tissue blood flow. A treatment of NE combined with fluid
      resuscitation has complex effects on tissue blood flow, ATP content, and pHi.

PMID- 10921586
TI  - Protection from ischemia-reperfusion induced severe acute renal failure by
      blocking E-selectin.
AB  - OBJECTIVE: Despite progress in renal replacement therapy and critical care
      medicine, acute renal failure (ARF) still carries a very high mortality rate.
      Neutrophil infiltration has been recognized as a hallmark in postischemic renal
      injury. Neutrophil recruitment requires adhesion molecules including E-selectin,
      which mediates leukocyte rolling and adhesion. This study aims to identify the
      role of E-selectin in ischemia-reperfusion-induced severe ARF. DESIGN:
      Prospective, controlled, experimental study. SETTING: University animal research
      laboratory. SUBJECTS: C57BL/6 wild-type mice or C57BL/6 mice gene-deficient for E
      selectin. INTERVENTIONS: Mice underwent 32-min bilateral renal ischemia or
      identical sham operations. After 4, 12, 24, or 48 hrs, kidneys were harvested and
      blood samples were taken. A separate group of wild-type mice received either
      antineutrophil serum or control serum 18 hrs before ischemia. Another group of
      wild-type mice was injected with function-blocking monoclonal E-selectin antibody
      or with control antibody 10 mins after reperfusion. Blood samples were taken 24
      hrs later. MEASUREMENTS AND MAIN RESULTS: Blood creatinine and urea nitrogen
      concentrations, as well as renal myeloperoxidase activity indicating neutrophil
      infiltration, were measured. Reducing neutrophil counts by antineutrophil serum
      showed that in this model, organ failure strongly depends on neutrophil counts at
      time of ischemia. E-selectin deficient mice showed lower creatinine and blood
      urea nitrogen concentrations than wild-type mice at 24 and 48 hrs (a reduction of
      60% to 80%). Kidneys of E-selectin deficient mice also revealed a lower
      myeloperoxidase activity maximum (75% reduction) at 24 hrs. Western blot analysis
      showed maximum E-selectin expression 24 hrs after ischemia-reperfusion.
      Immunostaining localized E-selectin to the endothelium of the peritubular
      capillary plexus. Compared with control antibody, postischemic injection of anti
      E-selectin antibody gave lower creatinine concentrations at 24 hrs, similar to
      that seen in E-selectin deficient mice. CONCLUSIONS: In this model, blocking E
      selectin even after onset of reperfusion protects from severe ARF, presumably by
      reducing postischemic neutrophil infiltration into the kidney. This suggests a
      new potential therapeutic perspective.

PMID- 10921587
TI  - Changes in circulating lymphocyte subpopulations and mitogen-stimulated response
      in a rat infusion model of intra-abdominal infection.
AB  - OBJECTIVE: To describe the alterations in circulating concentrations of immune
      cells as well as in in vitro mitogen-stimulated response in a recently developed
      rat model of intra-abdominal infection. DESIGN: Randomized, controlled study.
      SETTING: Government research facility. SUBJECTS: Male Sprague-Dawley rats.
      INTERVENTIONS: Infected animals received an intraperitoneal infusion of 6.0 x
      10(8) colony forming units of Escherichia coli during 12 hrs, whereas control
      rats received a sterile inoculum. All experimental animals underwent laparotomy
      and peritoneal lavage at the end of the infusion period. Blood samples were
      obtained 12 hrs, 36 hrs, or 7 days after the onset of infusion. Splenocytes were
      concomitantly harvested and assayed for response to the mitogens
      phytohemagglutinin (PHA), concanavalin A (Con A), and lipopolysaccharides, as
      well as for production of interleukin (IL)-2. MEASUREMENTS AND MAIN RESULTS:
      Infected rats showed a marked leukopenia (-82% for 36 hrs), with leukocyte counts
      returning to normal at 7 days. They also developed a marked lymphocytopenia
      throughout the study; this was achieved through comparable reductions in
      circulating T and B cells. Con A responses in both groups were similar for 7
      days. In contrast, splenocytes from infected animals showed reduced responses to
      lipopolysaccharides (-64%) and PHA (-30%) for 36 hrs compared with control
      splenocytes. IL-2 production from mitogen-stimulated splenocytes was suppressed
      in infected rats to 66% of that of control rats for 7 days. Suppressed PHA
      responses were not restored to control values in the presence of IL-2. For all of
      the parameters assessed, control animals showed either no significant changes or
      relatively fewer changes than infected rats. CONCLUSIONS: This model of intra
      abdominal infection is associated with changes in circulating concentrations of
      immune cells as well as with temporary functional defects in B and T cells,
      consistent with those often observed in patients with peritonitis. However, the
      role of IL-2 in limiting the adverse effects of infection in this experimental
      model seems to be limited. This model may be a useful tool in furthering our
      understanding of the pathophysiology of intra-abdominal infections and in
      assessing the efficacy of new therapeutic modalities.

PMID- 10921589
TI  - Pulmonary extraction and accumulation of lipid formulations of amphotericin B.
AB  - OBJECTIVE: To compare single-dose first pass uptake and accumulation of
      conventional amphotericin B (cAmB), liposomal amphotericin B (L-AmB), and
      amphotericin B lipid complex (ABLC) by the intact feline lungs. DESIGN:
      Prospective, controlled animal study. SETTING: Experimental laboratory in a
      university teaching hospital. SUBJECTS: A total of 31 spontaneously breathing,
      anesthetized cats. INTERVENTIONS: The pulmonary uptake of cAmB, L-AmB, and ABLC
      during a single passage through the pulmonary circulation, and the pulmonary
      retention of these drugs were studied after a bolus [cAmB, L-AmB, and ABLC, 1
      mg/kg (n = 9 each) and ABLC, 5 mg/kg (n = 4)] administration into the right
      ventricle. The amount of drug taken up by the lung during the first pass was
      measured from double indicator-dilution outflow curves. Animals were killed 30
      mins (cAmB, n = 4; L-AmB, n = 4), 1 hr (cAmB, n = 5; L-AmB, n = 5; ABLC, n = 5),
      or 6 hrs (ABLC, 1 mg/kg, n = 4; 5 mg/kg, n = 4) after drug administration.
      MEASUREMENTS AND MAIN RESULTS: The first-pass uptake of cAmB, L-AmB, and ABLC
      (mean +/- sD) by the lung was 73%+/-5%, 69%+/-8%, and 82%+/-6% of the injected
      dose (1 mg/kg), respectively (p > .05). ABLC (1 mg/kg) exhibited prolonged
      retention in the lung; 23% and 15% of the injected dose of ABLC remained in the
      lung 1 hr and 6 hrs after its administration, respectively. In contrast, cAmB and
      L-AmB exhibited rapid back diffusion of the drug out of the lung. After 30 mins,
      only 4% of the administered cAmB and L-AmB remained in the lung and after 1 hr
      only 1% to 2% was retained. Increasing the dose of ABLC from 1 mg/kg to 5 mg/kg
      did not alter pulmonary extraction of the drug; however, compared with the lower
      dose (1 mg/kg), higher concentrations of the drug were found in the lung 6 hrs
      after its administration. CONCLUSIONS: The results demonstrate a substantial
      extraction and accumulation of ABLC by the lung. This affinity for the lungs may
      have clinical implications for treating fungal infections that primarily involve
      the lung. Further studies are required to confirm the potential clinical
      relevance of these data.

PMID- 10921588
TI  - Reduced synthesis of inflammatory cytokines by a free radical scavenger after
      hemorrhagic shock in rats.
AB  - OBJECTIVES: Intestinal ischemia/reperfusion during hemorrhage and resuscitation
      may be a major trigger for cytokine expression. To assess whether free radicals
      produced on tissue reperfusion may play a role in the inflammatory response after
      hemorrhage, we tested the effect of a free radical scavenger on the production of
      inflammatory cytokines in a rat model of hemorrhagic shock. DESIGN: A
      prospective, controlled animal study. SETTING: A university research laboratory.
      SUBJECTS: Male Wistar rats. INTERVENTIONS: Hemorrhage was induced in anesthetized
      rats. by bleeding the animal to achieve a mean arterial blood pressure of 40 mm
      Hg for 60 mins. Resuscitation was then induced by reinjecting shed blood followed
      by NaCl 0.9% to maintain arterial blood pressure within control values. Treated
      rats received the free radical scavenger N-2-mercaptopropionyl glycine (MPG;
      20mg/kg iv bolus 30 mins before resuscitation followed by 20 mg/kg/hr).
      MEASUREMENTS AND MAIN RESULTS: MPG reduced the volume of saline necessary to
      restore blood pressure during resuscitation (untreated 85+/-6; MPG 35+/-5 mL/kg;
      p < .05). As compared with untreated rats, MPG markedly reduced the systemic and
      mesenteric plasma concentrations of tumor necrosis factor (TNF)-alpha (as
      measured by ELISA) and interleukin (IL)-6 (as measured by bioassay), assessed at
      the end of resuscitation. MPG also reduced TNF-alpha and IL-6 mRNA expression (as
      measured by reverse transcriptase-polymerase chain reaction) assessed in
      peritoneal macrophages isolated from shock rats. Finally, in vitro experiments
      showed that MPG also markedly reduced the mRNA expression and release of TNF
      alpha and IL-6 in peritoneal macrophages isolated from normal rats and subjected
      to hypoxia and reoxygenation. CONCLUSION: Reactive oxygen species contribute to
      the production of proinflammatory cytokines during posthemorrhage resuscitation.
      Free radicals scavengers may be a useful treatment in the prevention of the
      systemic inflammatory response that occurs in shock states.

PMID- 10921590
TI  - Ventilatory support by tracheal gas insufflation and chest vibration during
      bronchoconstriction.
AB  - OBJECTIVE: To determine whether chest wall vibration with tracheal gas
      insufflation during bronchoconstriction maintains gas exchange at lower airway
      and intrathoracic pressures than those that occur during positive pressure
      ventilation. DESIGN: Prospective study. SETTING: Experimental laboratory.
      SUBJECTS: Six anesthetized, paralyzed mongrel dogs (mean weight, 24.7+/-3.8 kg).
      INTERVENTIONS: Dogs were ventilated by two methods: mechanical ventilation (7
      breaths/min, 25 mL/kg tidal volume); and tracheal oxygen insufflation at 0.15 L x
      kg(-1) x min(-1) delivered with external chest wall vibration (29 Hz, 2 mm
      amplitude) of the dependent hemithorax. Bronchoconstriction was induced by
      methacholine infusion adjusted to double and quadruple the baseline airway
      resistance. Proximal mean airway pressure was kept equal for both modes of
      ventilation. MEASUREMENTS AND MAIN RESULTS: Airway pressure and flow, esophageal
      pressure, hemodynamic variables (cardiac output, systemic and pulmonary arterial
      pressures, pulmonary artery occlusion pressure) and gas exchange variables (PaO2,
      PaCO2, pH, shunt fraction, VO2) were measured. Peak airway pressure was lower (p
      < .05) with insufflation and vibration than with mechanical ventilation by 83.6%
      at baseline resistance, by 76.9% at twice baseline resistance, and by 76.8% at
      four times baseline resistance. Peak esophageal pressure was lower (p < .05)
      during insufflation with vibration by 68.5% at baseline resistance, by 87.5% at
      twice baseline resistance, and by 107% at four times baseline resistance. During
      insufflation with vibration, mild hypercapnia (PaCO2 58+/-3 torr (7.7+/-0.4 kPa)
      and pH 7.28+/-0.02) developed with moderate bronchoconstriction; more profound
      respiratory acidosis (PaCO2 137+/-41 torr (18.2+/-5.5 kPa) and pH 6.87+/-0.11)
      developed with severe bronchoconstriction. CONCLUSIONS: Tracheal gas insufflation
      with chest vibration supports gas exchange with permissive hypercapnia only
      during moderate, not severe, bronchoconstriction. Gas exchange was achieved at
      lower airway and intrathoracic pressures than those that developed during
      mechanical ventilation. The alveolar hypoventilation that occurred during
      insufflation with vibration indicates impaired CO2 elimination and suggests
      increased resistance to CO2 transport. This ventilation technique may confer
      therapeutic advantages over mechanical ventilation in the treatment of asthma.

PMID- 10921591
TI  - Endotracheal surfactant atomization: an alternative to bolus instillation?
AB  - OBJECTIVE: To investigate the effect of an intratracheal surfactant fog on
      oxygenation, blood pressure, distribution, and recovery rate as a pilot study to
      intratracheal surfactant aerosol. DESIGN: Prospective, randomized study. SETTING:
      University laboratory. SUBJECTS: A total of 15 New Zealand White rabbits.
      INTERVENTIONS: The anesthetized ventilated rabbits were surfactant-deprived by
      repeated lung lavages and then received 200 mg/kg of a 99mTc-labeled porcine
      surfactant (Curosurf) either as bolus or as intratracheal surfactant fog.
      MEASUREMENTS AND MAIN RESULTS: Blood gases and pressure were measured and
      distribution as well as recovery rate of the surfactant determined by means of
      the radio label (gamma camera images and lung processing with subsequent gamma
      counter measurements). Respiratory function normalized immediately, no difference
      could be found between the two groups with regard to PaO2, PaCO2, and blood
      pressure. Even distribution of the radiolabel was found with both methods, the
      bolus group showing a higher percentage of lung pieces with label concentrations
      of double average or more. Recovery rates were 82.5%+/-13.1% (mean +/- SD) in the
      bolus group and 86.5%+/-7.7% in the fog group. CONCLUSION: Endotracheal
      surfactant fog application is as effective as bolus instillation and may have a
      role in the treatment of adult respiratory distress syndrome. It has to be
      considered as a first step in producing an effective aerosol.

PMID- 10921592
TI  - Pulmonary surfactant is altered during mechanical ventilation of isolated rat
      lung.
AB  - OBJECTIVE: To test the hypothesis that the lung injury induced by certain
      mechanical ventilation strategies is associated with changes in the pulmonary
      surfactant system. DESIGN: Analysis of the pulmonary surfactant system from
      isolated rat lungs after one of four different ventilatory strategies. SETTING: A
      research laboratory at a university. SUBJECTS: A total of 45 Sprague-Dawley rats.
      INTERVENTIONS: Isolated lungs were randomized to either no ventilation (0-TIME)
      or to ventilation at 40 breaths/min in a humidified 37 degrees C chamber for
      either 30 mins or 120 mins with one of the following four strategies: a) control
      (CON, 7 mL/kg, 3 cm H2O positive end-expiratory pressure); b) medium volume, zero
      end-expiratory pressure (MVZP, 15 mL/kg, 0 cm H2O end-expiratory pressure); c)
      medium volume, high positive end-expiratory pressure (MVHP, 15 mL/kg, 9 cm H2O
      positive end-expiratory pressure); and d) high volume, zero end-expiratory
      pressure (HVZP, 40 mL/kg, 0 cm H2O end-expiratory pressure). MEASUREMENTS:
      Pressure-volume curves were determined before and after the ventilation period,
      after which the lungs were lavaged for surfactant analysis. MAIN RESULTS:
      Compared with 0-TIME, 30 mins of ventilation with the HVZP strategy or 120 mins
      of ventilation with CON and MVZP strategies caused a significant decrease in
      compliance. Groups showing a decreased compliance had significant increases in
      the amount of surfactant, surfactant large aggregates, and total lavage protein
      compared with 0-TIME. CONCLUSIONS: A short period of injurious mechanical
      ventilation can cause a decrease in lung compliance that is associated with a
      large influx of proteins into the alveolar space and with alterations of the
      pulmonary surfactant system. The changes of surfactant in these experiments are
      different from those seen in acute lung injury, indicating that they may
      represent an initial response to mechanical ventilation.

PMID- 10921593
TI  - Reduction of intracranial pressure by nimodipine in experimental pneumococcal
      meningitis.
AB  - OBJECTIVE: In this study, we investigated the effect of the calcium channel
      blocker nimodipine on the pathophysiologic alterations during experimental
      pneumococcal meningitis in rats. DESIGN: Prospective, controlled trial. SETTING:
      University center, animal laboratory. SUBJECTS: A total of 37 adult male Wistar
      rats (290-360 g). INTERVENTIONS: Meningitis was induced by the intracisternal
      injection of pneumococci. Anaesthetized animals were treated with nimodipine (30
      microg/kg/hr iv) either 15 mins before (pretreatment) or 5 hrs after
      (posttreatment) pneumococcal challenge. MEASUREMENTS AND MAIN RESULTS: Treatment
      with nimodipine (30 microg/kg/hr iv) significantly decreased the pneumococci
      induced rise in intracranial pressure irrespective of the time of administration.
      Moreover, pretreament with nimodipine also significantly reduced the pneumococci
      induced increase in cerebrospinal fluid white blood cell counts. To ascertain
      possible mechanisms of the beneficial effect, we investigated the influence of
      nimodipine on reactive oxygen species (ROS) and cytokine production. By using
      lucigenin-enhanced chemiluminescence, we found that nimodipine inhibited the
      pneumococci-induced production of ROS in human whole blood samples. Moreover,
      nimodipine significantly reduced the pneumococci-induced increase in the
      interleukin-6 concentrations in the cerebrospinal fluid. CONCLUSION: Our results
      demonstrate that nimodipine decreases the intracranial pressure during
      experimental pneumococcal meningitis, possibly by mechanisms including the
      reduction of ROS and interleukin-6 production.

PMID- 10921595
TI  - Jejunal mucosal nitric oxide production and substrate dependency during acute
      mesenteric hypoperfusion in pigs.
AB  - OBJECTIVE: Jejunal nitric oxide (NO) formation is impaired during mucosal
      hypoperfusion. This study was undertaken to investigate whether this phenomenon
      could result from a restricted mucosal availability of NO-synthase substrates,
      ie, oxygen and/or L-arginine. DESIGN: Controlled study using laboratory animals.
      SETTING: University animal research laboratory. SUBJECTS: Eighteen chloralose
      anesthetized, ventilated, juvenile Landrace domestic pigs. INTERVENTIONS:
      Mesenteric hypoperfusion was induced by intrapericardial infusion of Ringer's
      solution to achieve decreased cardiac output by creation of cardiac tamponade.
      MEASUREMENTS AND MAIN RESULTS: Animals were prepared for jejunal intraluminal
      perfusion with 150 mM NaCl or 3 mM L-arginine solution in an isolated intestinal
      segment and then subjected to cardiac tamponade. Jejunal mucosal NO formation was
      measured with a tonometric technique. Mesenteric blood flow was measured as
      portal blood flow, and mucosal perfusion was measured by laser Doppler flowmetry.
      Regional oxygen consumption and delivery were calculated from arterial and portal
      blood samples. Cardiac tamponade reduced jejunal NO formation (-52%), mesenteric
      oxygen delivery (-75%), oxygen consumption (-39%), and mucosal perfusion (-43%).
      Oxygenation of the jejunal intraluminal perfusate completely restored the
      intestinal NO levels within 30 mins, whereas presence of L-arginine was without
      effect. CONCLUSIONS: The study indicates that oxygen rather than L-arginine is
      the rate-limiting factor for mucosal NO production during acute reduced
      splanchnic perfusion.

PMID- 10921594
TI  - Directly measured tissue pH is an earlier indicator of splanchnic acidosis than
      tonometric parameters during hemorrhagic shock in swine.
AB  - OBJECTIVE: To compare tissue pH in the stomach, bowel, and abdominal wall muscle
      during hemorrhagic shock and recovery using tissue electrodes; also, to compare
      tissue electrode pH measurements to gastric intramucosal pH (pHi), gastric
      luminal PCO2, and PCO2 gap (gastric luminal CO2--arterial CO2) measured with an
      air-equilibrated tonometer. DESIGN: Prospective animal study. SETTING: University
      animal research laboratory. SUBJECTS: Eight anesthetized, mechanically ventilated
      Yorkshire swine. INTERVENTIONS: Hemorrhagic shock was initiated by withdrawing
      blood over a 15-min period to lower systolic blood pressure to 45 mm Hg. Shock
      was maintained for 45 mins and was followed by a 5-min resuscitation to normal
      blood pressure with a blood/lactated Ringer's (1:2) mixture. Recovery was
      monitored for 60 mins. MEASUREMENTS AND MAIN RESULTS: pH was measured with
      electrodes in the submucosa of the stomach, the submucosa of the small bowel, and
      the abdominal wall muscle. Gastric luminal PCO2 was measured with an air
      equilibrated tonometer and pHi and PCO2 gap were calculated. Each organ showed a
      different sensitivity to shock and resuscitation. The bowel pH responded most
      rapidly to the onset of hemorrhagic shock and had the largest change in tissue
      pH. The bowel also showed the most rapid recovery during resuscitation. The
      submucosal pH of the stomach responded more slowly than the bowel, but faster
      than the abdominal wall muscle pH, gastric PCO2 gap, or pHi. The smallest changes
      in organ pH as a result of hemorrhagic shock were seen in the abdominal wall
      muscle and the stomach as assessed by gastric tonometry. CONCLUSIONS: Direct
      measurement of tissue pH indicates that intra-abdominal organ pH varies during
      hemorrhagic shock. The small bowel pH changes the most in magnitude and rapidity
      compared with stomach pH or abdominal wall muscle pH. Tonometrically derived
      parameters were not as sensitive in the detection of tissue acidosis during shock
      and resuscitation as pH measured directly in the submucosa of the stomach or
      small bowel.

PMID- 10921596
TI  - Inhibition of p38 mitogen activate kinase attenuates the severity of pancreatitis
      induced adult respiratory distress syndrome.
AB  - OBJECTIVE: Adult respiratory distress syndrome (ARDS) is responsible for a
      significant portion of the morbidity and mortality during severe acute
      pancreatitis. Because inflammatory mediators such as tumor necrosis factor (TNF)
      alpha and nitric oxide (NO) produced within the lungs have been implicated in
      sepsis-induced ARDS, we aimed to determine the role of these mediators in
      pancreatitis-induced ARDS using a model whereby ascites from animals with
      pancreatitis is transferred to otherwise healthy animals resulting in pulmonary
      injury. DESIGN: Prospective, randomized, controlled trial. SETTING: Research
      laboratory at a university medical school. SUBJECTS: Pathogen-free Sprague-Dawley
      rats weighing 225-250 g. INTERVENTIONS: Sterile, endotoxin- and cytokine-free
      pancreatic ascites tested for interleukin (IL)-1beta , TNF-alpha, interferon
      gamma, and IL-6 was obtained from rats 18 hrs after the induction of severe,
      acute pancreatitis. Ascites was subsequently administered intravenously (20
      mL/kg) to healthy rats. Sham animals were administered intravenous saline.
      Healthy animals administered intravenous ascites were randomized to receive a
      single intraperitoneal injection of the p38 mitogen activated kinase inhibitor
      CNI-1493 (1 mg/kg) or vehicle. MEASUREMENTS: Pulmonary injury was assessed at 24
      hrs by histology and leukocyte and protein concentrations via bronchoalveolar
      lavage. Pulmonary TNF-alpha protein was detected by immunohistochemistry. Serum
      nitrite, as a measure of NO production, was measured utilizing the Griess
      reaction. MAIN RESULTS: After the intravenous administration of pancreatic
      ascites, the number of leukocytes and the protein concentration within the
      bronchoalveolar fluid were increased and pulmonary histology was worsened
      consistent with acute lung injury (all p < .001 vs. sham). Each of these
      variables of pulmonary injury was lessened in animals receiving CNI-1493 and
      intravenous ascites (p < .05 vs. vehicle). Pulmonary TNF-alpha protein and serum
      nitrites were decreased with the administration of CNI-1493 (p < .005 vs.
      vehicle). CONCLUSIONS: A component of pancreatic ascites other than endotoxin,
      bacteria, or cytokines (IL-1beta, TNF, interferon-gamma, or IL-6) is capable of
      inducing ARDS in healthy animals. Inhibition of p38 mitogen activated kinase
      decreases the pulmonary injury through attenuated production of TNF-alpha and NO
      suggesting a primary role for these mediators in pancreatitis-induced ARDS.

PMID- 10921597
TI  - Increased gut permeability and bacterial translocation in Pseudomonas pneumonia
      induced sepsis.
AB  - OBJECTIVE: Gut injury and barrier dysfunction may contribute to the pathogenesis
      of sepsis and multiple organ dysfunction syndrome. The objective of this study
      was to determine whether gut injury could be demonstrated in hyperdynamic,
      normotensive sepsis induced by Pseudomonas pneumonia. DESIGN: Randomized animal
      study. SETTING: University laboratory. SUBJECTS: Adult male Sprague-Dawley rats.
      INTERVENTIONS: Sepsis was induced by intratracheal instillation of Pseudomonas
      aeruginosa. MEASUREMENTS AND MAIN RESULTS: We measured gut mucosal and
      microvascular injury. In the first experiment, gut mucosal permeability was
      measured by 51Cr-EDTA uptake in control (n = 6), pneumonia 20-hr (n = 4), and
      pneumonia 40-hr (n = 4) groups. In the second experiment, microvascular
      permeability was measured by albumin extravasation, and morphologic abnormalities
      were scored in control (n = 6), pneumonia 20-hr (n = 9), and pneumonia 40-hr (n =
      11) groups. Bacterial translocation to mesenteric lymph nodes was determined in
      both experiments. Cardiac index increased significantly in the pneumonia compared
      with control rats (64+/-2.1, 68+/-1.3, vs. 46+/-2 mL/min/100 g, p < .05; all
      results are listed in the order of pneumonia 20-hr, pneumonia 40-hr, and control
      groups as mean +/- SEM). Mean blood pressure was normal and was not different
      between groups (112+/-3, 111+/-2, vs. 118+/-2 mm Hg). 51Cr-EDTA recovery in urine
      6 hrs after gavage increased significantly in both pneumonia groups vs. controls
      (17.5+/-2.2%, 17.9+/-7%, vs. 4+/-0.7%; p < .05). Albumin leak (tissue/plasma
      ratio) increased significantly in the middle and distal small intestine in the
      pneumonia 40-hr group vs. controls (0.68+/-0.05, 0.76+/-0.07, vs. 0.45+/-0.04, p
      < .05 in the middle small gut; 0.75+/-0.09, 0.85+/-0.07, vs. 0.51+/-0.05, p < .05
      in the distal small gut). Bacterial translocation to mesenteric lymph nodes
      increased significantly in pneumonia 40-hr rats vs. controls (positive culture
      67% vs. 8%; p < .05). CONCLUSIONS: This study demonstrates gut mucosal and
      microvascular injury and gut barrier dysfunction in normotensive sepsis secondary
      to bacterial pneumonia. The mechanism and significance of the injury need to be
      determined.

PMID- 10921598
TI  - Power spectral analysis of cardiovascular variability in critically ill
      neurosurgical patients.
AB  - OBJECTIVE: Patients with brain damage exhibit a number of changes in heart rate
      and cardiovascular control. The aim of this study was to relate changes in
      autonomic cardiovascular control seen in critically ill neurosurgical patients to
      the quality of subsequent outcome and survival. DESIGN: Prospective,
      longitudinal, outcome study. SETTING: Intensive care department of a university
      teaching hospital. PATIENTS: A total of 29 consecutive neurosurgical patients
      admitted for > or =2 days to the intensive care department with a Glasgow Coma
      Scale score < 13 who needed electrocardiographic and invasive arterial
      monitoring. INTERVENTIONS: Sampling of the electrocardiogram, respiratory rate,
      and arterial pressure into a personal computer was carried out for > or =60 mins.
      Power spectral analysis was then applied to the data by using a fast Fourier
      transformation. Arterial baroreflex sensitivity was determined as the gain of the
      transfer function between systolic arterial blood pressure and electrocardiograph
      R-R interval (RRI) variability. All surviving patients were followed up at 3
      months postadmission to measure quality of outcome. MEASUREMENTS AND MAIN
      RESULTS: There were reductions in the total power (p < .01) of RRI variability in
      those who subsequently died compared with those who survived. This was
      significant for very low frequency (p < .001) and low-frequency (LF) (p < .05)
      but not high-frequency (HF) bands (p = .11). Blood pressure variability, however,
      did not change between groups. Baroreflex sensitivity was 8.7+/-2.2 msecs/mm Hg
      for patients with a good later outcome and 4.4+/-1.5 msecs/mm Hg for patients who
      subsequently died (p = .03). Patients who recovered to a good quality outcome
      also had a raised LF/HF ratio in RRI (p = .05). CONCLUSION: A reduction in the
      total power variability of RRI and a lowered LF/HF ratio of the RRI are
      associated with a poor quality recovery or death after neurosurgical illness. A
      reduction in the baroreflex was specifically associated with death in this
      patient group.

PMID- 10921599
TI  - The mechanisms of platelet dysfunction during extracorporeal membrane oxygenation
      in critically ill neonates.
AB  - OBJECTIVE: Although bleeding associated with thrombocytopenia often complicates
      extracorporeal membrane oxygenation (ECMO), the mechanisms of platelet
      dysfunction during ECMO remain poorly understood. We investigated the role of
      matrix metalloproteinase (MMP)-2, which recently has been shown to mediate a
      novel pathway of platelet aggregation, in the platelet dysfunction induced by
      ECMO. DESIGN: Prospective longitudinal case study. SETTING: Level III neonatal
      intensive care unit. PATIENTS: Ten neonates treated with ECMO. INTERVENTION: ECMO
      procedure. MEASUREMENTS: Platelet counts and collagen-induced platelet
      aggregation ex vivo; plasma markers of platelet (soluble P-selectin) and
      endothelial (soluble E-selectin and total nitrite/nitrate) activation; plasma MMP
      2 and MMP-9 activities; and concentrations of tissue inhibitors of MMPs. MAIN
      RESULTS: During ECMO, time-dependent platelet activation, as evidenced by
      thrombocytopenia, decreased platelet aggregation, and increased plasma soluble P
      selectin concentrations were found in the absence of endothelial activation, as
      shown by normal plasma concentrations of soluble E-selectin and nitric oxide
      metabolites (nitrite/nitrate). There was a time-dependent increase in plasma MMP
      2 but not MMP-9 activity; tissue inhibitors of MMPs were not detected. Plasma
      soluble P-selectin concentrations significantly correlated with simultaneous
      plasma MMP-2 (r2 = .37, p < .0001) but not with MMP-9 activities. Platelet
      dysfunction persisted despite repeated platelet transfusions to maintain platelet
      counts >100 x 10(9)/L. CONCLUSIONS: ECMO resulted in the activation of platelets
      but not endothelial cells. During ECMO, platelet dysfunction persisted despite
      platelet transfusions. MMP-2 may play a role in the development of platelet
      dysfunction caused by ECMO.

PMID- 10921600
TI  - Procalcitonin and cytokine levels: relationship to organ failure and mortality in
      pediatric septic shock.
AB  - BACKGROUND: Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a
      mediator of the inflammatory response to infection, and thus influence outcome.
      OBJECTIVE: To investigate the relationship between PCT, interleukin (IL)-10,
      tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic
      shock. DESIGN: Prospective observational study. SETTING: A 16-bed pediatric
      intensive care unit of a university hospital. PATIENTS: A total of 75 children
      with septic shock having a median age of 43.1 months (range, 0.1-192 months).
      Children who had received antibiotics for >24 hrs were excluded. A total of 37
      patients (49%) had meningococcal disease, and 72 patients (96%) required
      mechanical ventilation. INTERVENTIONS: The pediatric risk of mortality (PRISM)
      score, multiple organ system failure (MOSF) score, duration of ventilation,
      length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured
      at admission to the intensive care unit. Sequential PCT levels were available at
      0 hrs and 24 hrs in 39 patients (52%). RESULTS: Observed mortality was 21/75
      (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p =
      .0001) were higher in children with higher MOSF scores. In survivors and
      nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was
      62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001),
      respectively. Area under the mortality receiver operating characteristic curve
      was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the
      PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no
      fall in PCT after 24 hrs treatment. These children had higher admission levels of
      IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a
      subsequent fall in PCT. Although the former did not have a higher median PRISM (p
      = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared
      with 9% (2 of 23) (p = .02). CONCLUSION: The admission PCT, like TNF and IL-10,
      is related to the severity of organ failure and mortality in children with septic
      shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic
      significance.

PMID- 10921602
TI  - Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are
      increased in the plasma of children with sepsis-induced multiple organ failure.
AB  - OBJECTIVES: To determine concentrations of circulating adhesion molecules
      endothelial (E)-selectin, intercellular adhesion molecule (ICAM)-1, and vascular
      cell adhesion molecule (VCAM)-1 in children with sepsis-induced multiple organ
      failure (MOF), and to determine associations among increased concentrations of
      these circulating adhesion molecules and important outcome measures. DESIGN:
      Prospective study. SETTING: University pediatric intensive care unit. PATIENTS: A
      total of 77 consecutive children with sepsis and 14 acutely ill children without
      sepsis. INTERVENTIONS: Plasma E-selectin, ICAM-1, and VCAM-1 concentrations and
      organ failure index (indicating number of failed organ systems) were determined
      in 77 children on days 1 and 3 of sepsis, and in 14 control children on pediatric
      intensive care unit day 1. Multivariate logistic regression analysis was used to
      determine associations between adhesion molecule concentrations and clinically
      relevant outcome measures. MEASUREMENTS AND RESULTS: Plasma concentrations of E
      selectin, ICAM-1, and VCAM-1 were increased in children with sepsis vs. control
      on day 1 (p < .05). Plasma VCAM-1 (but not ICAM-1 or E-selectin) was increased in
      children with more than three organ failures vs. children with less than three
      organ failures (p < .05). Plasma ICAM-1 and VCAM-1 (but not E-selectin)
      concentrations independently predicted number of organs failed and development of
      more than three organ failures. Plasma ICAM-1 and VCAM-1 also predicted mortality
      and development of sequential (pulmonary/hepatic/renal) MOF (p < .05).
      CONCLUSIONS: The pronounced and persistent increase in plasma VCAM-1 and ICAM-1
      that occurs in children with sepsis and persistent MOF may indicate a phenotypic
      change in endothelium toward a more proinflammatory state. Alternatively, the
      source for these adhesion molecules may be activated leukocytes and other cell
      types. Future studies are required to determine the role of ICAM-1 and VCAM-1 in
      the pathogenesis of sepsis-induced MOF.

PMID- 10921601
TI  - Using potentially life-shortening drugs in neonates and infants.
AB  - OBJECTIVE: To describe the frequency, background, and impact of decisions to give
      analgesic or other drugs that may, intentionally or unintentionally, shorten the
      life-span of severely ill neonates. SETTING: The Netherlands. DESIGN:
      Retrospective, cross-sectional study. PATIENTS: Questionnaires were mailed in The
      Netherlands to physicians reporting 338 consecutive deaths of infants under 1 yr
      of age from August through November 1995. INTERVENTIONS: None. MEASUREMENTS AND
      MAIN RESULTS: Questions were asked about medical end-of-life decisions preceding
      the death of the infant and about the decision-making process. Potentially life
      shortening drugs, mostly opioids, were given in 37% of all deaths. The estimated
      effect in terms of the shortening of life was <1 wk in 72% of all patients in
      whom the administration of potentially life-shortening drugs had been the most
      important end-of-life decision. Most decisions to administer such drugs were
      discussed with parents and colleagues. The decisions were discussed regarding
      virtually all patients in whom the physician had intended to hasten death; doses
      of opioids tended to be larger in this group. CONCLUSIONS: The frequency with
      which drugs that may shorten life are administered before the death of severely
      ill infants confirms the important role of modern medicine in dying in
      neonatology. Most physicians caring for neonates feel that palliative medication
      may be warranted in dying infants, even if it shortens life. A distinction
      between intentionally ending life and providing adequate terminal care by
      alleviating pain or other symptoms, which is important in moral and judicial
      terms, is probably not easily made for some of these patients.

PMID- 10921603
TI  - Early hyperthermia after traumatic brain injury in children: risk factors,
      influence on length of stay, and effect on short-term neurologic status.
AB  - OBJECTIVES: a) To determine the risk factors for early hyperthermia after
      traumatic brain injury in children; b) to identify the contribution of early
      hyperthermia to neurologic status at pediatric intensive care unit (PICU)
      discharge and to PICU length of stay in head-injured children. STUDY DESIGN:
      Observational cohort study. SETTING: PICU at a tertiary care, university medical
      center. PATIENTS: Children (n = 117) admitted to a PICU from July 1995 to May
      1997 with traumatic brain injury. These children had a median age of 5.4 yrs (3
      wks to 15.2 yrs old), and 33.4% were girls. MEASUREMENTS AND MAIN RESULTS: Early
      hyperthermia (temperature >38.5 degrees C within the first 24 hrs of admission)
      occurred in 29.9% of patients admitted to the PICU with traumatic brain injury.
      Risk factors predicting early hyperthermia included Glasgow Coma Scale score in
      the emergency department < or =8, pediatric trauma score < or =8, cerebral edema
      or diffuse axonal injury on initial head computed tomography scan, admission
      blood glucose >150 mg/dL (8.2 mmol/L), admission white cell count >14,300
      cells/mm3 (14.3 x 10(9) cells/L), and systolic hypotension. The presence of early
      hyperthermia significantly increased the risk for Glasgow Coma Scale score <13 at
      PICU discharge (odds ratio [OR] 9.7, 95% confidence interval [CI] 2.8, 24.4) and
      PICU stay > or =3 days (OR 13.8, CI 5.1, 37.5). When we used multiple logistic
      regression models including injury severity and hypotension, early hyperthermia
      remained an independent predictor of lower Glasgow Coma Scale score at PICU
      discharge (OR 4.7, CI 1.4, 15.6) and longer PICU length of stay (OR 8.5, CI 2.8,
      25.6). CONCLUSIONS: Early hyperthermia is independently associated with a measure
      of early neurologic status and resource utilization in children with traumatic
      brain injury serious enough to require PICU admission. These results support the
      prevention of hyperthermia in the management of traumatic brain injury in
      children. Further research is required to understand the mechanisms of this
      response and to identify appropriate preventive or therapeutic interventions.

PMID- 10921604
TI  - Relationship of pediatric overall performance category and pediatric cerebral
      performance category scores at pediatric intensive care unit discharge with
      outcome measures collected at hospital discharge and 1- and 6-month follow-up
      assessments.
AB  - OBJECTIVE: Given the current focus on outcomes, there is a crucial need for
      easily utilized measures that can effectively quantify morbidity or disability
      after a child's critical illness or injury. The purpose of this study is to
      significantly extend the research on two such promising measures: the Pediatric
      Overall Performance Category (POPC) and the Pediatric Cerebral Performance
      Category (PCPC). DESIGN: Cross-sectional analysis of a sample of pediatric
      intensive care unit (PICU) discharges and a prospective follow-up of this cohort
      of children. SETTING: Arkansas Children's Hospital. PATIENTS: Two hundred
      children (ranging in age from birth to 21 yrs) discharged from a PICU.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were collected at PICU
      discharge, hospital discharge, and 1- and 6-month follow-up assessments after
      hospital discharge. Measures utilized included the POPC (at PICU discharge), PCPC
      (at PICU discharge), Stanford-Binet Intelligence Scale, fourth edition (at
      hospital discharge), Bayley Scales of Infant Development, second edition (at
      hospital discharge), and the Vineland Adaptive Behavior Scales (at 1 and 6 months
      after discharge). Stanford-Binet Intelligence Quotients and Bayley Mental
      Developmental Index scores were significantly different across PCPC categories (p
      < .0001). Bayley Psychomotor Developmental Index scores and Vineland Adaptive
      Behavior Scales scores varied significantly across POPC categories (p < .0001).
      The test for linear trend was also significant for each of the comparisons.
      CONCLUSIONS: The results of this study offer additional support for the use of
      the PCPC and POPC. These brief and easily completed measures can provide useful
      information regarding probable outcomes for pediatric intensive care patients
      when more extensive psychometric testing is not feasible or desirable.

PMID- 10921605
TI  - Continuous measurement of backrest elevation in critical care: a research
      strategy.
AB  - OBJECTIVE: To develop and test a procedure for continuous measurement of backrest
      elevation in critical care for enhancing the precision of this measurement for
      research purposes. DESIGN: Descriptive, correlational. SETTING AND MEASUREMENTS:
      Backrest elevation, defined as the height of the head of the bed in degrees of
      elevation above horizontal, can be continuously monitored by using two
      transducers, one attached to the bed frame just distal to the head of the bed
      gatch and another attached to the bed frame at the top of the bed. By monitoring
      the differential head pressure between the two pressure channels, the height of
      the head of the bed can be calculated. A total of 30 random measurements of
      backrest elevation, from 0 degrees to 60 degrees, were taken by using the
      backrest elevation measurement on the bed frame, a handheld protractor, and the
      pressure differential between two transducers attached to the bed frame. Data
      collectors recorded one measurement independent of the other measurements. All
      measurements were conducted on the same bed. RESULTS: When the transduced method
      was compared with measurements by using a protractor, the Bland-Altman analysis
      technique yielded upper and lower limits of agreement of 8.93 degrees and -5.91
      degrees, respectively. The bias was 1.51 degrees, and the precision was 3.71
      degreees. CONCLUSIONS: The measurement technique described here was developed for
      research purposes to add precision to research studies examining the appropriate
      height of the backrest. However, the procedure could be used in a continuous
      quality improvement process to enhance compliance with patient care procedures
      involving backrest elevation or to confirm actual nursing practice and its
      correlation with patient outcome. In light of the risks associated with the use
      of supine positioning in critically ill and mechanically ventilated patients, the
      information gained from continuous measurement of backrest position could be an
      extremely valuable research tool.

PMID- 10921606
TI  - Defining the role of the pediatric critical care nurse practitioner in a tertiary
      care center.
AB  - OBJECTIVE: To describe the development and implementation of a pediatric critical
      care nurse practitioner role in a tertiary academic pediatric intensive care
      unit. DATA SOURCES: Selected relevant articles from the literature. DATA
      EXTRACTION/SYNTHESIS: Over the past two decades, the role of critical care nurse
      practitioners in neonatal and adult settings has developed. More recently, the
      role has emerged in the setting of pediatric critical care. Literature to date
      focuses on implementation of the nurse practitioner role in neonatal and adult
      critical care units, with limited publications on the role in the pediatric
      critical care arena. In addition, information on the practice of critical care
      nurse practitioners in tertiary care centers is lacking. We therefore, sought to
      describe the design, implementation, scope of practice, and outcomes to date of a
      pediatric nurse practitioner program in our pediatric critical care unit.
      CONCLUSIONS: A pediatric critical care nurse practitioner role can be implemented
      successfully in a tertiary center's pediatric intensive care unit. However,
      before integration of the pediatric critical care nurse practitioner into the
      health care team, definition of entry level requirements and the overall role
      with respect to scope of practice, daily operations, and professional practice is
      essential. Future endeavors should include evaluation of the impact of the
      pediatric critical care nurse practitioner on patient outcomes in the tertiary
      care center.

PMID- 10921607
TI  - Electrocardiogram-guided placement of enteral feeding tubes.
AB  - OBJECTIVE: To evaluate a new electrocardiogram guided method for placing
      nasoenteral feeding tubes in critically ill patients. DESIGN: Prospective case
      series. SETTING: Surgical intensive care unit in a tertiary center. PATIENTS: A
      total of 24 patients requiring enteral feeding tube placement entered the study.
      INTERVENTION: Standard 10-Fr flexible nasoenteral feeding tubes were inserted
      under direct vision by the nasal route. Before placement, two
      electrocardiographic reference recordings were made with the use of epigastric
      area skin electrodes, each 10 cm lateral to the midline 5 cm above the umbilical
      line. A continuous electrocardiographic tracing from the feeding tube was then
      monitored throughout the tube insertion process. A change in QRS axis
      simultaneous with electrocardiographic waveform change from reference point one
      to two was presumed to indicate tip passage beyond the midline and into the
      duodenum. Portable abdominal radiography was performed immediately after the
      procedure to confirm the anatomical location of the tube tip. MEASUREMENTS AND
      MAIN RESULTS: In four patients (17%), electrocardiographic tracings in both
      reference leads were identical and prevented further use of this method. In the
      remainder, electrocardiogram guided technique compared with portable abdominal
      radiography confirmed the correct position of the tube tip placed by
      electrocardiographic guidance. Sensitivity and specificity were 100% and 75%,
      respectively. CONCLUSION: This report describes a new technique of feeding tube
      placement. This simple and convenient bedside method allows prompt and safe
      initiation of enteral nutrition.

PMID- 10921608
TI  - Successful nonoperative management of delayed spontaneous esophageal perforation
      in patients with human immunodeficiency virus.
AB  - OBJECTIVE: To describe the clinical outcome of esophageal stenting for repair of
      distal esophageal perforation in one patient with septic shock and human
      immunodeficiency virus. DESIGN: Case report. SETTING: Medical-surgical intensive
      care units of one university teaching hospital. PATIENT: One patient with human
      immunodeficiency virus infection and septic shock in whom there was a delay in
      diagnosis of spontaneous perforation at the distal thoracic esophagus.
      INTERVENTION: A 10 cm x 2 cm silicone lined, partially coated, expandable metal
      stent was fluoroscopically placed in the distal esophagus at the perforation.
      Other treatment included chest tube thoracostomy, sump drainage of proximal
      esophagus, percutaneous gastrostomy, and antibiotics. MEASUREMENT AND MAIN
      RESULTS: Septic shock and the distal esophageal perforation were successfully
      treated with combined esophageal stenting, thoracostomy pleural drainage and
      antibiotics. Esophageal stenting was accomplished fluoroscopically with a
      partially coated, silicone-lined, expandable metal stent. CONCLUSION: Esophageal
      stenting, tube thoracostomy drainage, and antibiotics may be a management option
      for gravely ill patients with human immunodeficiency virus, esophageal
      perforation, and a delay in diagnosis. An optimal outcome requires a thoughtful,
      individualized approach and adherence to basic principles.

PMID- 10921609
TI  - Pneumoperitoneum: a review of nonsurgical causes.
AB  - OBJECTIVE: To review causes of nonsurgical pneumoperitoneum (NSP), identify
      nonsurgical etiologies, and guide conservative management where appropriate. DATA
      SOURCE: We conducted a computerized MEDLINE database search from 1970 to 1999 by
      using key words pneumoperitoneum and benign, nonsurgical, spontaneous,
      iatrogenic, barotrauma, pneumatosis, diaphragmatic defects, free air, mechanical
      ventilation, gynecologic, and pelvic. We identified 482 articles by using these
      keywords and reviewed all articles. Additional articles were identified and
      selectively reviewed by using key words laparotomy, laparoscopy, and
      complications. STUDY SELECTION: We reviewed all case reports and reviews of NSP,
      defined as pneumoperitoneum that was successfully managed by observation and
      supportive care alone or that required a nondiagnostic laparotomy. DATA
      SYNTHESIS: Each unique cause of nonsurgical pneumoperitoneum was recorded. When
      available, data on nondiagnostic exploratory laparotomies were noted. Case
      reports were organized by route of introduction of air into the abdominal cavity:
      abdominal, thoracic, gynecologic, and idiopathic. CONCLUSIONS: Most cases of NSP
      occurred as a procedural complication or as a complication of medical
      intervention. The most common abdominal etiology of NSP was retained
      postoperative air (prevalence 25% to 60%). NSP occurred frequently after
      peritoneal dialysis catheter placement (prevalence 10% to 34%) and after
      gastrointestinal endoscopic procedures (prevalence 0.3% to 25%, varying by
      procedure). The most common thoracic causes included mechanical ventilation,
      cardiopulmonary resuscitation, and pneumothorax. One hundred ninety-six case
      reports of NSP were recorded, of which 45 involved surgical exploration without
      evidence of perforated viscus. The clinician should maintain a high index of
      suspicion for nonsurgical causes of pneumoperitoneum and should recognize that
      conservative management may be indicated in many cases.

PMID- 10921610
TI  - Diabetes mellitus: a negative predictor for the development of acute respiratory
      distress syndrome from septic shock.

PMID- 10921611
TI  - Complexity, chaos, and incomprehensibility: parsing the biology of critical
      illness.

PMID- 10921612
TI  - Prostaglandin E1 and myocardial reperfusion injury.

PMID- 10921613
TI  - Shock resuscitation: have critical transcutaneous values now been defined?

PMID- 10921614
TI  - Would the colloid detractors please sit down!

PMID- 10921615
TI  - Predicted energy expenditure in critically ill children: problems associated with
      increased variability.

PMID- 10921616
TI  - Promotility agents in the intensive care unit.

PMID- 10921617
TI  - Neutrophils in sepsis, septic shock, and adult respiratory distress syndrome: how
      stiff is too stiff?

PMID- 10921618
TI  - High-frequency oscillatory ventilation and partial liquid ventilation: liquid
      breathing to a different beat (frequency)

PMID- 10921619
TI  - Mechanical ventilation and the diseased lung.

PMID- 10921620
TI  - Sepsis, cellular energy metabolism, and tissue adenosine triphosphate
      concentration.

PMID- 10921621
TI  - Shock resuscitation: is the glass half-empty or half full?

PMID- 10921622
TI  - Platelet dysfunction during extracorporeal membrane oxygenation: a new mechanism
      by which to control bleeding?

PMID- 10921623
TI  - End-of-life decisions in the neonatal intensive care unit: medical infanticide or
      palliative terminal care?

PMID- 10921624
TI  - Enteral nutrition: the right stuff at the right time in the right place.

PMID- 10921625
TI  - Predictive value of cytokines during acute severe pancreatitis.

PMID- 10921626
TI  - Dopamine in septic patients.

PMID- 10921627
TI  - Hepatosplanchnic oxygen dynamics.

PMID- 10921628
TI  - Arterial or venous cannulation: no transducer needed.

PMID- 10921629
TI  - Detection of arterial puncture during central venous catheterization: the
      intravenous tubing extension technique.

PMID- 10921630
TI  - Preventing complications of arterial puncture during central venous catheter
      insertion.

PMID- 10921631
TI  - Antibiotic resistance and exposure to different generation cephalosporins.

PMID- 10921632
TI  - Cross-linked hemoglobin and tumor necrosis factor response to endotoxemia.

PMID- 10921633
TI  - Results of anterior cruciate ligament reconstruction based on meniscus and
      articular cartilage status at the time of surgery. Five- to fifteen-year
      evaluations.
AB  - We sought to determine how the status of the meniscus and articular cartilage
      observed at the time of anterior cruciate ligament reconstruction affects results
      at 5 to 15 years after surgery. Objective follow-up was obtained on 482 patients
      at a mean of 7.6 years after surgery. Subjective follow-up was obtained on 928
      patients at a mean of 8.6 years after surgery. Patients with both menisci present
      had significantly better KT-1,000 arthrometer scores than did patients with any
      part of the medial or both menisci removed. Stepwise regression analyses
      determined that a partial or total medial or lateral meniscectomy and damaged
      articular cartilage significantly lowered the final subjective total score.
      Patients with both menisci present and normal articular cartilage had a mean
      subjective total score of 94, and 97% had normal or near normal radiographic
      ratings on a weightbearing 45 degrees posteroanterior radiographs. The overall
      International Knee Documentation Committee rating was normal or nearly normal for
      204 of 235 patients (87%) with both menisci present, 52 of 74 patients (70%) with
      partial or total lateral meniscectomies, 71 of 113 patients (63%) with partial or
      total medial meniscectomies, and 36 of 60 patients (60%) with both menisci
      removed. We concluded that the long-term subjective and objective results of a
      successful anterior cruciate ligament reconstruction are affected by the status
      of the menisci and articular surface.

PMID- 10921634
TI  - Effects of protective knee bracing on speed and agility.
AB  - We evaluated the effects of prophylactic knee braces on athlete speed and
      agility, as well as brace tendency to migrate. Thirty college football players in
      full gear ran a 40-yard dash and a four-cone agility drill wearing braces on both
      knees or no brace (control). Braces included the DonJoy Legend, Breg Tradition,
      OMNI-AKS 101W, McDavid Knee Guard, and models 1 and 2 of the Air Armor Knee and
      Thigh Protection System. Brace migration and subjective measures were recorded
      after each trial. In the 40-yard dash, times using Air Armor 1 and OMNI did not
      differ significantly from control. Times with other braces were significantly
      slower. In the four-cone drill, only the Breg times were significantly slower
      than control. The Air Armor 1 and McDavid braces showed significantly less
      superior/inferior migration in the 40-yard dash than other braces. In the four
      cone drill, the Air Armor 1 and 2 showed significantly less superior/inferior
      migration than other braces. These findings indicate that selected knee braces do
      not significantly reduce speed or agility. Braces showed a variable tendency to
      migrate, which could affect their protective function and athlete performance.
      This information will help athletes and coaches decide about knee-brace use
      during sports; studies are needed regarding whether braces protect against knee
      injury. This study does not constitute an endorsement of knee-brace use or
      efficacy.

PMID- 10921635
TI  - The effect of knee flexion angle and application of an anterior tibial load at
      the time of graft fixation on the biomechanics of a posterior cruciate ligament
      reconstructed knee.
AB  - Ten knees were studied using a robotic testing system under a 134-N posterior
      tibial load at five flexion angles. Three knee positions were used to study the
      effect of flexion angle at the time of graft fixation (full extension, 60
      degrees, and 90 degrees) and two were used to study the effect of anterior tibial
      load (60 degrees and 90 degrees). Knee kinematics and in situ forces were
      determined for the intact ligament and the graft for each reconstruction. Graft
      fixation at full extension significantly decreased posterior tibial translation
      compared with the intact knee by up to 2.9 +/- 2.9 mm at 30 degrees, while in
      situ forces in the graft were up to 18 +/- 35 N greater than for the intact
      ligament. Conversely, posterior tibial translation for graft fixation at 90
      degrees was significantly greater than that of the intact knee by up to 2.2 +/-
      1.1 mm at all flexion angles; in situ forces decreased as much as 33 +/- 30 N.
      When an anterior tibial load was applied before graft fixation at 90 degrees of
      flexion, posterior tibial translation did not differ from the intact knee from 30
      degrees to 120 degrees, while the in situ force in the graft did not differ from
      the intact ligament at full extension, 60 degrees, and 120 degrees of flexion.
      These data suggest that graft fixation at full extension may overconstrain the
      knee and elevate in situ graft forces. Conversely, fixation with the knee in
      flexion and an anterior tibial load best restored intact knee biomechanics.

PMID- 10921636
TI  - Inferior capsular shift procedure in athletes with multidirectional instability
      based on isolated capsular and ligamentous redundancy.
AB  - Twenty-five athletes (26 shoulders) who underwent an inferior capsular shift
      procedure for multidirectional glenohumeral instability based on isolated
      capsular and ligamentous redundancy were evaluated at a median of 54 months
      (range, 25 to 113) after the operation. Twenty-one athletes (84%) returned to
      their preinjury activity level at a median of 5 months after surgery. Of 21
      athletes involved in sports using overhead motions, 16 (76%) returned to their
      previous sport after the operation, and 12 (57%) were still active in this sport
      at the preinjury level at follow-up. According to the Rowe score, 23 shoulders
      (88%) were excellent or good. The University of California at Los Angeles score
      for 24 shoulders (92%) was excellent or good. The operations on two shoulders
      (8%) failed. One patient had a spontaneous redislocation, and one had recurrent
      subluxations. Nine contralateral shoulders had a history of significant
      instability; four of these had undergone Bankart repair. We concluded that
      athletes who have multidirectional instability based on isolated capsular and
      ligamentous redundancy can be successfully treated by an inferior capsular shift
      preserving the subscapularis tendon insertion. We found a high rate of return to
      demanding upper extremity sports in our patients, range of motion was restored in
      the majority of shoulders, and the failure rate after a median of 54 months was
      acceptable.

PMID- 10921637
TI  - Characteristics of patients with primary acute lateral patellar dislocation and
      their recovery within the first 6 months of injury.
AB  - We prospectively studied the characteristics and early recovery of an unselected
      population of patients who had acute first-time lateral patellar dislocation. The
      recovery program used standardized rehabilitation, emphasizing range of motion,
      muscle strength, and return of function. Patients returned to stressful
      activities including sports as tolerated when they regained full passive range of
      motion, had no effusion, and when quadriceps muscle strength was at least 80%
      compared with the noninjured limb. Seventy-four patients met the enrollment
      criteria; 37 men and 37 women. The average age was 19.9 years, and preinjury
      sports participation was similar to that of ligament-injury patients. Four
      percent of patients (N = 3) had a history of birth complications, 3% (N = 2) had
      a history of lower extremity problems as an infant or child, and 9% (N = 7) had a
      family history of patellar dislocation. Radiographs revealed a 50% incidence (N =
      37) of patella alta; all patients demonstrated lateral patellar overhang.
      Patients regained range of motion (mean, 0 degrees to 132 degrees) by 6 weeks.
      Sports participation remained significantly reduced throughout the first 6 months
      after injury, with the greatest limitations in kneeling and squatting. At 6
      months, 58% of patients (N = 43) noted limitation in strenuous activities. The
      patients who had acute primary patellar dislocation were young and active. Most
      injuries occurred during sports, and few patients had abnormal physical features,
      contradicting any stereotype of an overweight, sedentary, adolescent girl whose
      patella dislocates with little or no trauma.

PMID- 10921638
TI  - Intrinsic risk factors for the development of anterior knee pain in an athletic
      population. A two-year prospective study.
AB  - Many variables have retrospectively been associated with the presence of anterior
      knee pain. Very few prospective data exist, however, to determine which of these
      variables will lead to the development of anterior knee pain. It was our purpose
      in this study to determine the intrinsic risk factors for the development of
      anterior knee pain in an athletic population over a 2-year period. Before the
      start of training, 282 male and female students enrolled in physical education
      classes were evaluated for anthropometric variables, motor performance, general
      joint laxity, lower leg alignment characteristics, muscle length and strength,
      static and dynamic patellofemoral characteristics, and psychological parameters.
      During this 2-year follow-up study, 24 of the 282 students developed
      patellofemoral pain. Statistical analyses revealed a significant difference
      between those subjects who developed patellofemoral pain and those who did not
      concerning quadriceps and gastrocnemius muscle flexibility, explosive strength,
      thumb-forearm mobility, reflex response time of the vastus medialis obliquus and
      vastus lateralis muscles, and the psychological parameter of seeking social
      support. However, only a shortened quadriceps muscle, an altered vastus medialis
      obliquus muscle reflex response time, a decreased explosive strength, and a
      hypermobile patella had a significant correlation with the incidence of
      patellofemoral pain. We concluded that the latter four parameters play a dominant
      role in the genesis of anterior knee pain and we therefore deem them to be risk
      factors for this syndrome.

PMID- 10921639
TI  - The association between athletic training time and the sagittal curvature of the
      immature spine.
AB  - Strenuous physical activity is known to cause structural abnormalities in the
      immature vertebral body. Concern that exposure to years of intense athletic
      training may increase the risk for developing adolescent hyperkyphosis in certain
      sports, as well as the known association between hyperkyphosis and adult-onset
      back pain, led us to examine the association between cumulative hours of athletic
      training and the magnitude of the sagittal curvature of the immature spine. A
      sample of 2,270 children (407 girls and 1,863 boys) between 8 and 18 years of age
      were studied. An optical raster-stereographic method was used to measure the mid
      sagittal curvatures of the surface of the back while the subject was in the
      upright standing position to quantify the angles of thoracic kyphosis and lumbar
      lordosis. These data were then correlated with self-reported hours of training
      measured by interview and questionnaire. The possible effects of age, sex, sport,
      and upper and lower body weight training were investigated. The results in these
      young athletes showed that larger angles of thoracic kyphosis and lumbar lordosis
      were associated with greater cumulative training time. Gymnasts showed the
      largest curves. Lack of sports participation, on the other hand, was associated
      with the smallest curves. Age and sex did not appear to affect the degree of
      curvature.

PMID- 10921641
TI  - Risk of injury during alpine and telemark skiing and snowboarding. The equipment
      specific distance-correlated injury index.
AB  - Estimation of injury risk in alpine sports is difficult. We present a new method
      of calculating an injury index related to the distance traveled on ski or
      snowboard. The distance-correlated injury index equals the number of injuries per
      100,000 km traveled distance. This injury index can also be correlated to the
      type of equipment used. The equipment-specific distance-correlated injury index
      is the same as the distance-correlated injury index, but it is sport-specific. We
      found the distance-correlated injury index for alpine skiing to be 3.9 (95% Cl =
      2.8 to 5.4); for snowboarding, 13.5 (95% Cl = 8.3 to 22.0); and for telemark
      skiing, 3.0 (95% Cl = 1.0 to 9.4), suggesting a three- to four-times higher
      incidence of injuries requiring hospital treatment among snowboarders than among
      alpine and telemark skiers.

PMID- 10921640
TI  - Tenocytes from ruptured and tendinopathic achilles tendons produce greater
      quantities of type III collagen than tenocytes from normal achilles tendons. An
      in vitro model of human tendon healing.
AB  - Type I collagen is the main collagen in tendons; type III collagen is present in
      small amounts. Ruptured Achilles tendons contain a significantly greater
      proportion of type Ill collagen, which predisposes them to rupture. We used an in
      vitro model to determine whether tenocytes from Achilles tendons that were
      ruptured (N = 22), nonruptured (N = 7), tendinopathic (N = 12), and fetal (N = 8)
      show different behavior. Samples of Achilles tendon were digested with
      collagenase and the released tenocytes were collected. Primary tenocyte cultures
      were established and subsequently cultured onto glass coverslips. Once a
      confluent monolayer was obtained, the cell populations were "wounded" by scraping
      a pipette tip along the surface. The cultures were further incubated for either
      1, 4, 8, 12, 16, or 24 hours, and production of types I and II collagen was
      assessed by immunostaining. In cultures from ruptured and tendinopathic tendons,
      there was increased production of type Ill collagen. Athletic participation
      places excess stress on the Achilles tendon, which could potentially lead to
      areas of microtrauma within the tendon. These areas may heal by the production of
      type III collagen, which is an abnormal healing response. Accumulation of such
      episodes of microtrauma could resuit in a critical point where the resistance of
      the tissue to tensile forces is compromised and tendon rupture occurs.

PMID- 10921642
TI  - A prospective study of high school wrestling injuries.
AB  - We performed a prospective study to evaluate injury patterns in a large
      population of high school wrestlers during one season. Preseason screening was
      performed on 458 male wrestlers from 14 different high schools. Certified
      athletic trainers submitted detailed weekly team and individual injury reports.
      There were 219 injuries in 418 wrestlers followed throughout the season for an
      overall injury incidence of 52 injuries per 100 wrestlers per season and an
      injury rate of 6.0 injuries per 1,000 exposures. The most commonly injured areas
      were the shoulder (24%) and knee (17%). Injured wrestlers were an average of 5
      months older and had a 32% higher experience level than noninjured wrestlers.
      Wrestlers with ligamentous laxity suffered fewer shoulder injuries than the other
      wrestlers. The majority of injuries occurred in practice (63%), although the
      injury rate was higher in match competitions. Sixty-eight percent of practice
      injuries occurred during hard wrestling, 23% during drills, and 9% during
      conditioning. The most common wrestling situation resulting in injury was the
      takedown position (68%). Our results show that the older and more experienced
      wrestler may be at greater risk of injury. Hard wrestling during practice and the
      takedown position resulted in the highest occurrence of injury.

PMID- 10921643
TI  - The distribution of injuries in men's Canada West university football. A 5-year
      analysis.
AB  - We conducted a prospective cohort study from 1993 to 1997 to determine the
      frequency and severity of injury in men's Canada West university football. The
      Canadian Intercollegiate Sport Injury Registry was used to document baseline
      preseason data, daily athlete participation, and subsequent injury from five
      varsity football teams. An injury was defined as "any injury resulting in one or
      more complete or partial sessions of time loss" or "any concussion or transient
      neck neurologic injury." The annual proportion of injured athletes ranged from
      53.5% to 60.4%, with a 5-year total of 1,811 injuries. Regression analysis
      indicated that the rate of nonconcussion, nonneck neurologic injuries increased.
      Concussion (N = 110), hamstring strain (N = 88), and brachial plexus (N = 84)
      injuries were the most common, specific injury diagnoses. Knee injuries resulted
      in the highest rate of severe (greater than or equal to 7 sessions of time loss)
      injury and resulted in the most time loss (3,350.5 sessions). Ligament sprains
      and muscle strains and spasms accounted for approximately half of all injury
      diagnoses. A total of 1,173 injuries (65%) were related to contact between
      players or between players and other obstacles. Future studies should be
      conducted to identify risk factors for the ultimate purpose of implementing
      injury prevention strategies.

PMID- 10921644
TI  - Preoperative sizing of meniscal allografts in meniscus transplantation.
AB  - The purpose of this study was to determine the accuracy of radiographic and
      magnetic resonance imaging techniques in preoperative sizing for allograft
      meniscus transplantation. Twelve cadaveric knee specimens underwent sequential
      radiographs, magnetic resonance imaging scans, and arthrotomy. Meniscus
      dimensions were measured in multiple planes for the purpose of determining
      accuracy of imaging studies in comparison with actual meniscus dimensions.
      Overall, magnetic resonance imaging proved only slightly more accurate than
      conventional radiography. The mean difference between magnetic resonance imaging
      measurements and actual meniscus dimensions was 2.25 +/- 2.04 mm. The mean
      difference between radiographic measurements and actual meniscus dimensions was
      2.35 +/- 1.79 mm. Neither imaging technique was accurate for measuring individual
      meniscus dimensions, with only 35% of images measuring within 2 mm of actual
      meniscus dimensions. Using less stringent criteria for accuracy (within 5 mm),
      radiography and magnetic resonance imaging were 79% and 83% reliable,
      respectively. Failure to obtain true anteroposterior or lateral images (15
      degrees of external and internal rotation) increased measurement inaccuracy.
      Intraobserver agreement was significantly higher for magnetic resonance imaging
      than for radiography. Further research into the development of alternative
      techniques for more reliable meniscus sizing and better understanding of the
      tolerance for meniscus size mismatch is necessary.

PMID- 10921645
TI  - Closed-Wedge osteotomy for osteochondritis dissecans of the capitellum. A 7- to
      12-year follow-up.
AB  - This article details a 7- to 12-year follow-up of seven young male baseball
      players with osteochondritis dissecans of the capitellum that we treated using
      closed-wedge osteotomy. This procedure was established by Yoshizu in 1986 for the
      treatment of "Little League elbow." The bone of the capitellum was revascularized
      and remodeled within 6 months in all seven patients. Six of the patients were
      able to return to full athletic activity and continued to play baseball.
      Radiographic assessment during the follow-up study revealed minimal
      osteoarthritic change and suggests that the treatment is useful for such an
      injury.

PMID- 10921646
TI  - Repair of chronic ruptures of the distal biceps tendon using flexor carpi
      radialis tendon graft.
AB  - Five patients with chronic distal biceps tendon ruptures underwent tendon repair
      using double-looped flexor carpi radialis tendon graft. Fixation was performed
      with suture anchors through a single anterior incision. All patients had
      excellent functional results at a minimum 2-year follow-up.

PMID- 10921647
TI  - Comparison of knee joint cartilage thickness in triathletes and physically
      inactive volunteers based on magnetic resonance imaging and three-dimensional
      analysis.
AB  - The objective of this study was to employ quantitative magnetic resonance imaging
      for the analysis of knee joint cartilage thickness in triathletes and physically
      inactive volunteers. The right knee joints of nine male triathletes (10 hours
      training per week for at least 3 years) and nine inactive male volunteers (<1
      hour of physical activity per week throughout life) were imaged with a previously
      validated fat-suppressed gradient echo sequence. The cartilage plates were
      reconstructed three-dimensionally, and the cartilage thickness was computed
      independently of the original section orientation with a three-dimensional
      Euclidian distance transformation. There was a high interindividual variability
      of the mean and the maximal cartilage thickness values in all surfaces, both in
      the triathletes and in the inactive volunteers. In the patella, the femoral
      trochlea, and the lateral femoral condyle, the mean and maximal cartilage
      thickness values were slightly higher in the triathletes, but they were somewhat
      lower in the medial femoral condyle, and in the medial and lateral tibial
      plateau. However, the differences did not attain statistical significance. These
      results are unexpected in view of the functional adaptation observed in other
      musculoskeletal tissues, such as muscle and bone, in which a more obvious
      relationship with the magnitude of the applied mechanical stress has been
      observed.

PMID- 10921649
TI  - Internal and external tibial rotation strength after anterior cruciate ligament
      reconstruction using ipsilateral semitendinosus and gracilis tendon autografts.
AB  - The internal and external tibial rotation torques of subjects who had undergone
      anterior cruciate ligament reconstruction using semitendinosus and gracilis
      tendon grafts were measured to determine whether harvest of the tendons results
      in weakness of tibial internal and external rotation. Cybex NORM dynamometer
      examinations were performed to measure internal and external tibial torque at
      angular velocities of 60, 120, and 180 deg/sec in 23 subjects. The sex-specific
      average torque data of the reconstructed limbs were compared with those of the
      contralateral limbs. Relative internal and external torque scores were calculated
      for each subject by subtracting the peak torque of the reconstructed knee from
      that of the contralateral knee. These relative scores were averaged and compared
      with the null hypothesis that each score should be statistically similar to zero.
      Subjects were evaluated at an average of 51 +/- 40 months postoperatively. The
      mean relative internal torque scores of the reconstructed limbs showed a
      statistically significant decrease from those of the contralateral limbs at all
      angular velocities. The mean relative external torque scores of the reconstructed
      limbs were statistically similar to those of the contralateral limbs at all
      angular velocities. Subjects who had undergone ligament reconstruction using
      semitendinosus and gracilis tendons demonstrated internal tibial rotation
      weakness in their reconstructed knees compared with their contralateral knees at
      all angular velocities tested. These results suggest that semitendinosus and
      gracilis tendon harvest causes weakness of internal tibial rotation.

PMID- 10921650
TI  - Regeneration of the semitendinosus tendon harvested for anterior cruciate
      ligament reconstruction. Evaluation using ultrasonography.
AB  - In a prospective study, 40 consecutive patients who underwent anterior cruciate
      ligament reconstruction with doubled semitendinosus and gracilis tendon
      autografts were examined pre- and postoperatively by ultrasound to investigate
      the anatomy of the donor site before and after the harvest of the tendons. The
      patients underwent ultrasonography at 2 weeks and 1, 2, 3, 6, 12, 18, and 24
      months postoperatively. A total of 298 postoperative sonographic evaluations were
      performed. The semitendinosus tendon was imaged in the sagittal and axial planes:
      structure and margins were evaluated with the sagittal views; thickness and width
      were measured with the axial views. In all cases the following sequence of
      healing was documented: 2 weeks after surgery the semitendinosus tendon site was
      occupied by an area of increased thickness and decreased echogenicity, suggesting
      the presence of traumatic edema of the soft tissue surrounding the tenotomy. At 1
      month, an irregular hypoechoic structure appeared in a near-anatomic position; at
      2 months after surgery, thickness, width, and cross-sectional area of this
      structure were significantly greater than preoperatively. The amount of
      regenerated tissue increased up to that seen in the tissue of the 6-month
      examinations, which also showed a more uniform echostructure. The scans performed
      at 1 year showed distinct edges and reduction in thickness and width. At 18 and
      24 months the echogenicity of the structure occupying the donor site was very
      similar to that of the normal semitendinosus tendon. However, this structure was
      clearly identified about 4 cm proximal to the pes anserinus, revealing a more
      proximal insertion of the regenerated semitendinosus tendon.

PMID- 10921648
TI  - Comparison of tibial tunnel enlargement after anterior cruciate ligament
      reconstruction using patellar tendon autograft or allograft.
AB  - This retrospective study was designed to compare tibial tunnel enlargement in
      patients with autograft or allograft anterior cruciate ligament reconstructions.
      The changes were related to position of the tibial tunnel and clinical outcome.
      Twenty-six patients with autograft reconstructions and 41 with allograft
      reconstructions were studied at a mean follow-up of 59 months (range, 41 to 84)
      after surgery. The average tunnel enlargement on the anteroposterior view was 2.2
      mm (SD, 2.5) for autografts and 2.8 mm (SD, 2.1) for allografts. On the lateral
      view, the tunnel enlargement was 2.6 mm (SD, 2.4) and 3.4 mm (SD, 2.6) for
      autografts and allografts, respectively. No significant differences were found
      between the autograft and allograft groups. A trend was found in the correlation
      between the position of the tibial tunnel and the tunnel enlargement: more
      anteriorly placed tunnels had more enlargement. The changes in tunnel diameter
      did not relate to knee functional score or laxity. There was a significant
      correlation between malposition of the tibial tunnel and poor clinical scores. A
      significant negative correlation was found between postoperative follow-up time
      and tunnel enlargement in both groups. We conclude that placement of the tibial
      tunnel is a determining factor in tibial tunnel enlargement and clinical knee
      scores after anterior cruciate ligament replacement with an autograft or
      allograft. Tunnel enlargement tends to be less at a longer postoperative follow
      up.

PMID- 10921651
TI  - The relationship of the infrapatellar branches of the saphenous nerve to
      arthroscopy portals and incisions for anterior cruciate ligament surgery. An
      anatomic study.
AB  - The purposes of this study were 1) to carefully define the anatomic distribution
      of the infrapatellar branches of the saphenous nerve, 2) to provide the surgeon
      with reliable parameters for where the nerve is most commonly encountered, and 3)
      to provide specific surgical recommendations to minimize the risk of nerve
      injury. To accomplish these goals, we dissected 20 cadaveric, fresh-frozen,
      matched-pair knees. Calipers were used to measure the distance from the nerve to
      three clinically relevant and easily reproducible landmarks: the inferior pole of
      the patella, the medial border of the patella at its midpoint, and a point 2 cm
      medial to the patellar ligament at the level of the joint line. Distances were
      recorded with the knees in extension and in 90 degrees of flexion to examine the
      effect of dynamic knee motion on nerve position. We consistently found two main
      trunks of the nerve that traverse the knee primarily in a medial to lateral but
      somewhat proximal to distal direction. Because of this, we recommend that
      incisions for arthroscopy portals be made in a horizontal fashion to decrease the
      likelihood of nerve injury. Measured from both the inferior pole of the patella
      and the medial border of the patella, the nerve moved distally with knee flexion.
      We therefore recommend that incisions across the anterior aspect of the knee be
      made with the knee in flexion. In 8 of our 20 specimens, the nerve was actually
      found at the landmark located 2 cm medial to the patellar ligament. This is an
      extremely high-risk area and should be avoided if possible.

PMID- 10921652
TI  - The benefit of a single-leg strength training program for the muscles around the
      untrained ankle.
AB  - Severe ankle injuries can require extended periods of immobilization that
      adversely affect the strength of the ankle muscles. We have investigated a single
      leg strength training program of the muscles surrounding the ankle to determine
      if it produces a crossover benefit for the contralateral ankle muscles. Twenty
      subjects without any history of ankle injuries were randomly divided into a
      control and a training group. Both groups underwent isokinetic testing of the
      ankle muscles at the beginning and end of an 8-week period. The control group
      maintained normal activities between the tests. Half of the training group
      trained the dominant leg only and the other half trained the nondominant leg only
      for the 8-week period, three times per week. The subjects who trained the
      dominant leg improved peak torque values by 8.5% in the trained leg and 1.5% in
      the untrained leg. Similarly, the subjects who trained the nondominant leg
      improved peak torque values by 9.3% in the trained leg and 3.5% in the untrained
      leg. In contrast, the control group showed no significant change in peak torque,
      power, or endurance between the initial and final tests. With improvements in
      peak torque as high as 40% in the trained leg and a crossover benefit of 19% in
      the untrained leg in eccentric inversion, this strength training technique
      deserves further investigation in an injured population where the benefits may be
      more substantial.

PMID- 10921653
TI  - Chronic complete hamstring avulsion causing foot drop. A case report.

PMID- 10921655
TI  - Total avulsion fracture of the coronoid tubercle caused by baseball pitching. A
      case report.

PMID- 10921654
TI  - Acute traumatic tear of the latissimus dorsi tendon from its insertion. A case
      report.

PMID- 10921656
TI  - A case of apophysitis of the proximal patella.

PMID- 10921657
TI  - Injuries to the shoulder in the throwing athlete. Part two: evaluation/treatment.
AB  - In part one of this three-part series (March/April 2000), I concentrated on
      summarizing the biomechanics of the normal throwing shoulder and the
      pathophysiology of injury. A classification of injury was presented that was
      based on the principles contained in that article. Part two of this series will
      focus on the evaluation and treatment of injuries, expanded from an understanding
      of the principles learned in part one. The ability to perform a skillful
      examination, and thus develop an accurate diagnosis, is the foundation for
      treatment. Fortunately, many difficulties encountered in a thrower's shoulder can
      be treated with a nonoperative approach. However, in instances where conservative
      measures fail, an improved understanding of the pathophysiology of injury and the
      development of improved surgical techniques are leading to more accurate
      diagnoses and more successful rates of return of the athlete to a premorbid level
      of activity.

PMID- 10921658
TI  - Arthroscopic management of glenohumeral instability.
AB  - There has been substantial development of techniques for performing arthroscopic
      surgery of the shoulder over the past 20 years. A multitude of arthroscopic
      techniques have been developed in an attempt to manage the unstable glenohumeral
      joint while decreasing surgical morbidity. The results obtained with arthroscopic
      stabilization have been widely variable. This review will examine the current
      status of arthroscopic management of glenohumeral instability. The techniques and
      results of arthroscopic stabilization for primary anterior glenohumeral
      instability, recurrent anterior instability, and multidirectional instability
      will be discussed. A brief discussion on thermal capsulorrhaphy is included.

PMID- 10921659
TI  - The effect of neuromuscular training on the incidence of knee injury in female
      athletes: a prospective study.

PMID- 10921660
TI  - Management of severe lower abdominal or inguinal pain in high-performance
      athletes.

PMID- 10921661
TI  - Perceptual and mnemonic matching-to-sample in humans: contributions of the
      hippocampus, perirhinal and other medial temporal lobe cortices.
AB  - Two questions were addressed by the present study. The first was whether the
      previously reported item recognition deficit which is shown by amnesic patients
      may be due to a perceptual rather than a memory deficit. To address this question
      a group of amnesic patients were tested on a 14-choice forced-choice visual item
      recognition test which included a "simultaneous" condition in which the sample
      remained visible during the matching decision and a zero second delay. Eacott,
      Gaffan and Murray (1994) have reported an impairment in simultaneous matching-to
      sample following perirhinal damage in monkeys. In our amnesic patients, a deficit
      was found only after filled delays of 10 seconds or longer and this was also the
      case for a subgroup of patients whose damage included the perirhinal cortex. The
      second question, which arose from the model of Aggleton and Brown (1999), was
      whether performance on the DMS task would remain intact following selective
      damage to the hippocampus. We tested a patient with bilateral damage to the
      hippocampus on the 14-choice DMS task and found that her performance was not
      significantly impaired at delays of up to 30 seconds.

PMID- 10921662
TI  - Sex differences in the perception of tactile simultaneity.
AB  - A tactile simultaneity task was used to investigate the effects of sex on
      simultaneity thresholds. Participants were required to judge whether pairs of
      tactile stimuli delivered unimanually or bimanually were simultaneous. Unimanual
      stimulation delivered stimuli to the same cerebral hemisphere, while bimanual
      stimulation resulted in the delivery of one stimulus to each hemisphere,
      therefore requiring interhemispheric transmission before judging simultaneity.
      The data of 114 right-handed participants were analysed. Females (N = 56)
      perceived simultaneity at longer intervals than males (N = 58) when bimanual
      stimulation was received. Furthermore, males had shorter interhemispheric
      transmission times (10.9 ms) than those of females (15.0 ms). The results also
      provided some support for the predictions of the Hemispheric Equivalence Model of
      temporal processing since bimanual simultaneity thresholds were longer than
      unimanual; and unimanual stimulation of the left vs right hand did not differ. An
      advantage for stimulation of right hand first (vs left first) in the bimanual
      condition was small (2.7 ms), and was the only prediction of the Left Hemisphere
      Specialisation Model to receive support. A modification of the Equivalence Model
      which allows for a slight left hemispheric advantage is proposed.

PMID- 10921663
TI  - Implicit semantic evaluation of object symmetry and contralesional visual denial
      in a case of left unilateral neglect with damage of the dorsal paraventricular
      white matter.
AB  - It is well documented that right brain damaged patients with left unilateral
      neglect may show unconscious processing of contralesional stimuli. However, the
      anatomical correlates of this phenomenon are still not well defined. Here we
      report the case of a neglect patient with a circumscribed lesion of the dorsal
      parietal-occipital white matter showing clear implicit processing of the
      contralesional side of line drawings and object based neglect. The patient was
      able to perform correct semantic analysis of the symmetry (or asymmetry) of the
      drawings. Additional testing disclosed denial of the existence of the
      contralesional side of asymmetrical geometrical shapes with correct perception of
      symmetrical ones and of shapes without the left side. These findings provide
      direct evidence supporting a critical role of the dorsal visual system in the
      activation of conscious representations of visual stimuli.

PMID- 10921664
TI  - Dissociation between distal and proximal left limb agraphia and agraphesthesia in
      a patient with a callosal disconnection syndrome.
AB  - A few neuropsychological studies have suggested the existence of bilateral
      hemispheric representations for the proximal parts of the limbs in humans. We
      report the case of a patient who presented with a callosal disconnection
      syndrome, which at a later stage of disease became restricted to left agraphia,
      left agraphesthesia and left auditory extinction. The anomic character of the
      agraphesthesia was demonstrated. Tactile naming was normal, which allows us to
      conclude that separate callosal pathways related to the left language areas
      transmit information for graphesthesia and tactile naming. Agraphia and
      agraphesthesia were not observed when the proximal part of the left upper limb
      was utilized. These observations support the conclusion that writing and
      graphesthesia with the proximal part of the limb can be mediated by the
      ipsilateral cortex.

PMID- 10921665
TI  - Visual implicit memory deficit and developmental surface dyslexia: a case of
      early occipital damage.
AB  - This study reports the case of EBON, a fifteen-year-old right-handed female
      Swedish student, who suffered an early medial/dorsal occipital brain lesion and
      showed a clearly defined pattern of developmental surface dyslexia. EBON and 17
      controls were examined with within and cross-modality (visual and auditory) word
      stem completion tasks together with tasks requiring free-recall and recognition
      for visually and auditory presented words. Compared to age-matched controls, EBON
      was found to show a significant deficit of visual priming following visual
      presentation, and a deficit approaching significance following auditory
      presentation. Explicit memory and visual and spatial abilities were not
      significantly different from controls. Therefore, EBON represents the first
      childhood case establishing the role of occipital regions in visual priming, as
      well as illustrating a profile of surface reading difficulty as a developmental
      consequence of this locus of lesion.

PMID- 10921666
TI  - Number processing and calculation in a case of visual agnosia.
AB  - We describe the performance of a brain-damaged subject who suffered from visual
      agnosia leading to major difficulties in generating and exploiting visual
      representations from long-term memory. His performance in a physical judgement
      task in which he was required to answer questions about the visual shapes of
      Arabic numerals reflected his agnosic problems. However, he showed no impairment
      in usual number processing and calculation tasks. This case shows that, despite
      some commonalities in number and object processing, actual numerical processes
      are not affected by visual agnosia and can be preserved even when fine visual
      processes are impaired.

PMID- 10921667
TI  - Perceiving left and imagining right: dissociation in neglect.
AB  - Signor Piazza, a patient with a left parieto-occipital haemorrhage and a right
      thalamic stroke, showed severe right personal neglect (e.g. touching own body
      parts) and right perceptual neglect in tasks with (e.g. cancelling tasks) or
      without (e.g. description of a complex picture) motor response. He had also right
      sided neglect dyslexia (including single words), without language impairments.
      However, the patient also presented with a clear left-sided deficit in the
      representational domain (e.g. imagery tasks). Signor Piazza's pattern of
      performance suggests dissociation between imagery and perception within the
      neglect syndrome.

PMID- 10921668
TI  - Absence of hemispheric dominance for mental rotation ability: a transcranial
      Doppler study.
AB  - Mean blood flow velocity (MFV) of the middle cerebral arteries was monitored in
      19 healthy, adult, right-handed subjects during the resting phase and the
      execution of a series of neuropsychological tests: two right/left discrimination
      tasks, two mental rotation paradigms (the Ratcliff's test and a cube comparison
      test) and a phonemic fluency task, which was utilised as an internal control. In
      the group as a whole, the Ratcliff's test was associated with a significant
      bilateral increase in MFV versus both the resting state (right: p < .000001,
      left: p < .000001) and right/left discrimination tasks (task 1: right: p = .003,
      left: p = .005; task 2: right: p = .001, left: p = .001). The cube comparison in
      turn produced a significant increase in MFV versus both the baseline conditions
      (right: p < .000001, left: p < .000001) and the Ratcliff's test (right: p = .01,
      left: p = .002). As expected, the fluency task was associated with a significant
      asymmetric increase in cerebral perfusion (left > right: p = .0001). Increasing
      task difficulty (right/left discrimination < Ratcliffs test < cube comparison)
      was paralleled by a roughly proportional rise in MFV values (right: r = .424, p <
      .01; left: r = .331, p = .01). In conclusion, we were able to demonstrate that
      (1) in addition to the amount of MFV variation due to right/left discrimination
      (when required), mental rotation per se causes a bihemispheric activation
      irrespective of the experimental paradigm; (2) the MFV variation is proportional
      to the difficulty of the tasks.

PMID- 10921669
TI  - Topographical disorientation consequent to amnesia of spatial location in a
      patient with right parahippocampal damage.
AB  - We describe a patient who selectively lost the ability to orient himself in the
      environment after a stroke involving the right parahippocampal gyrus. The
      neuropsychological assessment showed a specific pattern of impairment of
      topographical memory; the patient recognised and recalled environmental landmarks
      but was unable to recall their spatial location. This study provides evidence
      that different forms of topographical disorientation may be related to distinct
      mechanisms of cognitive dysfunction. Furthermore, neuroimaging data suggest that
      a lesion of the right parahippocampal gyrus is critically related to pure
      topographical disorientation.

PMID- 10921670
TI  - The failure of language comprehension at sentence and phrasal levels in a patient
      who can speak normally.
AB  - An unexpected dissociation between intact propositional speech and impaired
      language comprehension was observed in a right handed patient following a right
      hemisphere stroke. Although CHO's comprehension was intact at the single word
      level, his ability to comprehend a wide range of sentence structures was
      profoundly impaired. This deficit was observed in the context of normal sentence
      production both with regard to semantic and syntactic content. This case provides
      further evidence for the independence of on-line language input and output
      systems.

PMID- 10921671
TI  - Noncommutability of the N + 0 arithmetical rule: a case study of dissociated
      impairment.
AB  - It has been shown that some arithmetical problems are stored in the form of
      individual facts representations (e.g., 3 x 4 = 12) whereas others are solved by
      general stored rules (e.g., 0 x N = 0). We describe the performance of a brain
      damaged subject who presented a mild impairment in arithmetical fact retrieval.
      Although her performance was almost perfect for rule-based problems in all
      arithmetical operations, she was severely impaired for 0 + n problems in contrast
      with her relatively good performance for the corresponding n + 0 problems. This
      dissociation extends to addition the noncommutability of arithmetical rules
      described in multiplication.

PMID- 10921672
TI  - The quill passes.

PMID- 10921673
TI  - Total arch replacement using aortic arch branched grafts with the aid of
      antegrade selective cerebral perfusion.
AB  - BACKGROUND: We report our clinical experience with total arch replacement using
      aortic arch branched graft in an attempt to determine the independent predictors
      of both in-hospital mortality and neurologic outcome. METHODS: We studied 220
      consecutive patients who underwent total arch replacement using aortic arch
      branched graft between May 1990 and June 1999. All operations were performed with
      the aid of hypothermic extracorporeal circulation, antegrade selective cerebral
      perfusion, and open distal anastomosis. RESULTS: The overall in-hospital
      mortality rate was 12.7%. Multivariable analysis showed independent determinants
      of in-hospital mortality to be chronic renal failure, long pump time,
      participation in early series, and shock. Postoperative permanent neurologic
      dysfunction was 3.3%. On multivariable analysis, old cerebral infarct and pump
      time were independent determinants of permanent neurologic dysfunction. The
      selective cerebral perfusion time had no significant influence on in-hospital
      mortality or neurologic outcome. The 5-year survival rate including in-hospital
      deaths was 79% +/- 6%. CONCLUSIONS: Selective cerebral perfusion allows increased
      ease of performance of total arch replacement, a complex and time-consuming
      procedure, and helps reduce periprocedural mortality and morbidity in patients
      with aortic arch aneurysm and those with acute aortic dissection.

PMID- 10921674
TI  - Antegrade selective cerebral perfusion during operations on the thoracic aorta:
      our experience.
AB  - BACKGROUND: Various methods of cerebral protection have been used during aortic
      arch operations. Deep hypothermia with circulatory arrest is the most common
      technique but has a limited safe period for circulatory arrest. Selective
      cerebral perfusion has been introduced to prolong this safe period. We reviewed
      our experience with antegrade selective cerebral perfusion during surgical repair
      of the thoracic aorta. METHODS: Between November 1996 and December 1998, 57
      consecutive patients were operated on for aortic arch aneurysms using selective
      cerebral perfusion. Forty-one were men (71.9%), and 16 were women. The mean age
      was 63.2 years. Thirty-seven patients had chronic aneurysms, and 20 had type A
      acute dissection. Preoperative, intraoperative, and postoperative factors were
      analyzed by univariate and multivariate analysis to identify predictors of early
      mortality and transient neurologic dysfunction. RESULTS: There were no permanent
      neurologic deficits. The early mortality rate was 8.8% (5 patients). Multivariate
      analysis revealed preoperative renal failure (p = 0.0338) and repeat thoracotomy
      for bleeding (p = 0.0201) to be independent risk factors for early mortality. The
      factor postoperative cardiac complications (p = 0.0368) was the only independent
      predictor of transient neurologic dysfunction, and it occurred in 3 patients
      (5.3%). CONCLUSIONS: The present study confirmed that preoperative renal failure
      and repeat thoracotomy for bleeding are significant predictors of mortality in
      aortic arch operations using selective cerebral perfusion and that cerebral
      perfusion time has no influence on the postoperative outcome. We believe that
      selective cerebral perfusion is an optimal technique of cerebral protection
      during operations on the aortic arch.

PMID- 10921675
TI  - Replacement of the aortic valve and ascending aorta with a valved stentless
      composite graft: technical considerations and early clinical results.
AB  - BACKGROUND: Replacement of the aortic valve and the ascending aorta with a
      conduit consisting of a mechanical valve and a Dacron tube has become a fairly
      common procedure. Commercially available conduits employing xenografts are rarely
      used for the same purpose, because if a reoperation becomes necessary due to
      degeneration of the valve prosthesis, usually the entire conduit must be
      replaced. A composite graft with a stentless valve, such as we describe in this
      article, avoids this problem, because in case of reoperation only the valve cusps
      need to be resected and the tube graft may be left in place. METHODS: Surgical
      technique of replacement of the aortic valve and the ascending aorta with a
      stentless composite graft and early results of the procedure are presented.
      RESULTS: Hemodynamics of the graft soon after surgery were excellent, with an
      average systolic gradient of 8 mm Hg and no regurgitation across the valve. There
      were two reoperations for bleeding in the early postoperative period.
      CONCLUSIONS: The stentless composite graft we describe provides excellent
      hemodynamics, has no need for anticoagulation, and is expected to offer a benefit
      in case of reoperation.

PMID- 10921676
TI  - Valve-sparing aortic root replacement (remodeling/reimplantation) in acute type A
      dissection.
AB  - BACKGROUND: High reoperation rates after supracommissural tube graft replacement
      for acute type A dissection due to sinus of Valsalva dilation have been reported.
      Valve-sparing operations focusing on the replacement of the sinus of Valsalva are
      an appealing alternative. The applicability of these techniques in acute type A
      dissection remains debatable and results are limited. METHODS: From 1992 to 1998,
      20 patients with acute type A dissection received a valve-sparing aortic root
      replacement. Two different types of aortic valve-sparing operations were
      performed: the remodeling technique in 11 patients and the reimplantation
      technique in 9 patients. Patients were followed for 26 +/- 18 months.
      Echocardiographic studies were performed every 6 months. RESULTS: There were 2
      early postoperative deaths and no late death, no reoperation, and no
      thromboembolic events. The latest echocardiographic studies of the 18 survivors
      showed a competent valve in 12 and a trivial aortic valve insufficiency in 6
      patients. The mean aortic valve pressure gradient was 4.3 +/- 1.3 mm Hg.
      CONCLUSIONS: These midterm results support the surgical strategy of valve-sparing
      aortic root replacement in patients with acute type A dissection.

PMID- 10921677
TI  - Ascending aortic atheroma assessed intraoperatively by epiaortic and
      transesophageal echocardiography.
AB  - BACKGROUND: The presence of ascending aortic atheroma is a known risk for
      systemic emboli or early saphenous vein graft failure if unrecognized at the time
      of cardiopulmonary bypass. METHODS: This study prospectively compared
      intraoperative omniplane transesophageal echocardiography (TEE) and epiaortic
      ultrasound (EAU) images in 22 patients (6 women, 16 men, age 66 +/- 8 years)
      before surgical manipulation of the ascending aorta. Atheroma lesion severity was
      scored: 1 = normal, 2 = nonprotruding intimal thickening (> 2 mm), 3 = atheroma
      less than 4 mm +/- Ca++, 4 = atheroma greater than or equal to 4 mm +/- Ca++, and
      5 = any size mobile or ulcerated lesion +/- Ca++. The ascending aorta between the
      aortic valve and innominate artery was divided into proximal, middle, and distal
      segments. A total of 66 segments were evaluated. RESULTS: Although the overall
      agreement of scores between procedures was 75.8%, significantly more lesions were
      identified by EAU (15) than by TEE (5) (p < 0.03). TEE failed to identify lesions
      in the middle and distal segments of the aorta with a score of more than 3.
      CONCLUSIONS: Although atheromatous lesions were identified in the ascending aorta
      by both ultrasound modalities, the results suggest that intraoperative EAU may
      have an advantage over TEE for surgeons assessing target sites for surgical
      procedures involving the ascending aorta.

PMID- 10921678
TI  - Posterior pericardial approach for ascending aorta-to-descending aorta bypass
      through a median sternotomy.
AB  - BACKGROUND: Bypass grafting for repeat operation or complex forms of descending
      aortic disease is an alternative approach to decrease potential complications of
      anatomic repair. METHODS: Between December 1985 and February 1998, 17 patients
      (13 men, 4 women; mean age, 47.6 +/- 18.5 years) underwent ascending aorta-to
      descending aorta bypass through a median sternotomy and posterior pericardial
      approach. Indications for operation were coarctation or recoarctation of aorta in
      8 patients, Takayasu's aortitis in 2, prosthetic aortic valve stenosis associated
      with coarctation of aorta, complex descending aortic arch aneurysm, reoperation
      for chronic descending aortic dissection, long-segment stenosis of descending
      aorta, acquired coarctation after repair of traumatic transection of descending
      aorta, severe aortic atherosclerosis, and false aneurysm of descending aorta
      after repair of coarctation in 1 patient each. Concomitant procedures were
      performed in 12 patients. RESULTS: No early or late mortality has occurred.
      Follow-up was 100% complete and extended to 12 years (mean, 2.7 +/- 3.3 years).
      No late graft-related complications have occurred; 1 patient had successful
      repair of perivalvular leak after mitral valve replacement, and 1 patient had
      replacement of lower descending and abdominal aorta. CONCLUSIONS: Exposure of the
      descending aorta through the posterior pericardium for ascending aorta-descending
      aorta bypass is a safe alternative and particularly useful when simultaneous
      intracardiac repair is necessary.

PMID- 10921679
TI  - Selective perfusion of segmental arteries in patients undergoing thoracoabdominal
      aortic surgery.
AB  - BACKGROUND: Reattachment of segmental arteries is one method used to prevent
      paraplegia associated with thoracoabdominal aortic repair. Nevertheless, even
      when important segmental arteries are reattached, ischemia causing spinal injury
      may occur during anastomosis. METHODS: In 27 patients undergoing thoracoabdominal
      aortic repair, we attempted to perfuse the segmental arteries to be reattached
      with catheters connected to the distal bypass circuit. To identify perioperative
      risk factors for spinal ischemia, we examined changes in spinal somatosensory
      evoked potentials. RESULTS: A median value of four segmental arteries were
      perfused in 20 (74%) of the 27 patients. Changes in somatosensory evoked
      potential indicative of spinal ischemia were observed in 13 patients (48%). The
      only risk factor associated with changes in evoked potentials revealed by a
      multivariate analysis was prolonged aortic cross-clamp time (> 120 minutes). Of
      the 2 patients who suffered paraplegia, one had the longest clamp time and the
      other showed spinal cord necrosis due to embolic shower. CONCLUSIONS: Despite
      selective perfusion of segmental arteries, spinal ischemia associated with aortic
      cross-clamping may occur when clamping is prolonged over 120 minutes. Most of the
      changes appear to be reversible, however.

PMID- 10921680
TI  - Selective intercostal arterial perfusion during thoracoabdominal aortic aneurysm
      surgery.
AB  - BACKGROUND: This clinical study evaluated changes in motor evoked potentials
      (MEP) elicited by direct cerebral cortical stimulation and evoked spinal cord
      potentials (ESCPs) elicited by direct spinal cord stimulation during selective
      intercostal arterial perfusion for thoracoabdominal aortic aneurysm (TAAA)
      repair. We also determined the efficacy of this perfusion method for prevention
      of paraplegia. METHODS: Two kinds of ESCPs and MEPs were monitored during the
      prosthetic replacement step for TAAA surgeries. We performed selective
      intercostal arterial perfusion from the T7 intercostal artery to the L1
      intercostal artery through a small piece of Dacron graft while monitoring spinal
      cord potentials in five cases of TAAA. RESULTS: The MEP amplitude decreased after
      clamping the aorta but quickly recovered after selective perfusion of intercostal
      arteries. Other spinal cord potentials did not change during the reconstruction
      of intercostal arteries. Postoperative paraplegia or parapalesis did not occur in
      any of the patients. CONCLUSIONS: Monitoring of MEPs during selective intercostal
      arterial perfusion was a useful adjunct to prevent postoperative paraplegia in
      TAAA surgery.

PMID- 10921681
TI  - Stentless aortic valve replacement with Freestyle or Toronto SPV: an early
      comparison.
AB  - BACKGROUND: Stentless aortic xenograft valves have been developed to overcome the
      disadvantages of conventional stented prostheses. We have implanted two new
      aortic bioprostheses: the Medtronic Freestyle and the St. Jude Toronto SPV. Early
      results are compared. METHODS: Forty-four Freestyle valves were implanted using a
      freestanding total root technique. Fourteen subcoronary Toronto SPV bioprostheses
      were implanted. Sixty-four percent of both groups (28 of 44 Freestyle and 9 of 14
      Toronto SPV) underwent concurrent procedures. RESULTS: Ischemic time was 117 +/-
      21 minutes for Freestyle and 124 +/- 19 minutes for Toronto SPV. There were no
      operative deaths or valve-related reoperations. Aortic valve area was 1.83 +/-
      0.51 cm2 for Freestyle and 1.80 +/- 0.51 cm2 (p = 0.89) for Toronto SPV.
      Transvalvular gradient was 8.03 +/- 4.09 mm Hg for Freestyle and 12.4 +/- 1.82 mm
      Hg (p = 0.002) for the Toronto SPV. Aortic regurgitation was not experienced in
      any Freestyle patients, while Toronto SPV patients were graded as none to trace
      79% (11 of 14), mild 14% (2 of 14), and moderate 7% (1 of 14). CONCLUSIONS:
      Aortic valve replacement with the Freestyle and Toronto SPV required equal time
      for implantation and had equal effective orifice areas. Freestyle had lower
      transvalvular gradient and less aortic insufficiency without increasing morbidity
      or mortality.

PMID- 10921682
TI  - Valve repair in mitral regurgitation complicated by severe annulus calcification.
AB  - BACKGROUND: Valvuloplasty has significant advantages over valve replacement for
      mitral regurgitation, but the presence of severe calcification of the mitral
      valve apparatus has been thought to preclude successful valve reconstruction in
      general. The purpose of this report is to assess the results of valvuloplasty in
      patients with severe mitral regurgitation having extensive calcification
      extending from the mitral annulus to underlying myocardium and parts of the
      papillary muscles. METHODS: Thirty-seven adult patients with severe mitral
      regurgitation and calcification were operated on between April 1990 and January
      1998. Twenty-six patients had degenerative disease, 4 had acute bacterial
      endocarditis, 6 had postrheumatic fever, and 1 patient had Marfan's disease. The
      valve repair comprised of en bloc decalcification with extensive leaflet
      debridement and reconstruction of the annulus. Autologous pericardium was used in
      patch-extended endocardial annuloplasty or leaflet repair. Valve competence was
      retained after correction of regurgitation by sliding atrioplasty, rotation
      paracommissural sliding plasty, cusp remodeling, or chordal repair. All patients
      required a prosthetic annuloplasty. RESULTS: Follow-up echocardiography at 47
      months (range, 3 to 92 months) showed no or only trivial mitral regurgitation in
      33 patients; 3 had grade I-II mitral regurgitation and 1 required valve
      replacement after 3 months. Freedom of reoperation at 1 and 5 years was 94.6%. At
      last examination, 33 patients were in New York Heart Association functional class
      I and 3 in class I-II; there has been no mortality and no thromboembolic events.
      CONCLUSIONS: Valvuloplasty can be safely and successfully carried out in patients
      suffering from regurgitation associated with severe calcification of the mitral
      apparatus. With encouraging beneficial midterm results, we suggest patients with
      calcified valves should not be excluded from mitral repair.

PMID- 10921683
TI  - Mechanical assist strategy using the BVS 5000i for patients with heart failure.
AB  - BACKGROUND: The BVS 5000i external pulsatile assist device is used to support
      patients with reversible cardiogenic shock. Its low cost and potential for
      insertion without cardiopulmonary bypass make it an attractive option. METHODS:
      Nineteen status I patients failing inotropic support were treated with the BVS
      5000i with the intention of short-term bridge to transplant. Fourteen patients
      received left ventricular support whereas 5 received biventricular support.
      Cardiopulmonary bypass was used in less than 50% of patients. RESULTS: Median
      support time was 7 days. The 2 myocarditis patients were weaned from support.
      Twelve patients were transplanted and there were 5 deaths on support. Overall 14
      of 19 were transplanted or weaned. One-year survival was 79%. Median hospital
      stay was 31 days. CONCLUSIONS: The BVS 5000i can be used for short-term
      mechanical assist toward transplantation in selected patients for whom a donor
      can be expected soon. The device may provide a cost-effective, short-term
      strategy to optimize end-organ function before orthotopic heart transplant,
      particularly for patients who are predictably not ideal to be discharged with
      implantable left ventricular assist device treatment.

PMID- 10921684
TI  - Demand dynamic cardiomyoplasty: mechanograms prove incomplete transformation of
      the rested latissimus dorsi.
AB  - BACKGROUND: In dynamic cardiomyoplasty, standard stimulation produces high
      fatigue resistance but also undesirable dynamic characteristics of the latissimus
      dorsi (LD). Based on results of intermittent stimulation in animals we introduced
      demand stimulation, a lighter regimen of LD activity-rest stimulation, and the
      mechanogram, a noninvasive method to determine the contractile characteristics of
      LD wrap. METHODS: Surgery and standard stimulation was according to the technique
      of Carpentier and Chachques, demand stimulation and LD wrap mechanogram were as
      we previously described. The LD contraction is synchronized to heart systole by
      mechanogram and echocardiography, and extent of transformation by tetanic fusion
      frequency analysis. A total of 22 patients were studied to date. Data for the 8
      subjects who attained 6-month follow-up are reported. Four of them were lightly
      stimulated from the conditioning period, whereas 4 others were converted to light
      and then demand stimulation after years of standard stimulation. Patients were
      followed up with respect to survival, functional class, hospital admission rate,
      medication used, cardiopulmonary exercise testing, and LD wrap mechanography.
      RESULTS: Latissimus dorsi wrap slowness reverses by the activity-rest regimen,
      even after years of standard stimulation (Tetanic fusion frequency of 11 +/- 2 Hz
      after standard stimulation vs 30 +/- 3 Hz after demand regimen, p < 0.0001).
      After demand dynamic cardiomyoplasty there are no deaths. Quality of life is
      substantially improved with significant reduction of heart failure symptoms (New
      York Heart Association class: preoperative 3.0 +/- 0.0, post-demand dynamic
      cardiomyoplasty 1.5 +/- 0.2, p < 0.0001). In the subgroup of patients lightly
      stimulated from LD conditioning, exercise capacity tends to increase over
      preoperative values more than 2 years after operation (VO2 max: preoperative 12.3
      +/- 0.7 vs 16.6 +/- 1.7 post-demand dynamic cardiomyoplasty, p = 0.05).
      CONCLUSIONS: Demand stimulation and mechanography of the LD wrap are safe
      procedures that could offer long-term benefits of dynamic cardiomyoplasty to
      patients with pharmacologically intractable heart failure.

PMID- 10921686
TI  - Early outcome and graft patency in mammary artery grafting of left anterior
      descending artery with sternotomy or anterior minithoracotomy.
AB  - BACKGROUND: The main objective of this study was to retrospectively compare early
      outcome and graft patency in patients who underwent coronary artery bypass
      grafting with the internal thoracic artery to the left anterior descending artery
      via an anterior minithoracotomy or median sternotomy and without the use of
      extracorporeal circulation. METHODS: One hundred thirty consecutive patients were
      studied. Median sternotomy was performed in 77 patients and anterior
      minithoracotomy in 53 patients. RESULTS: There were no differences in early
      clinical data or persistent postoperative pain between the groups. Early graft
      patency was 88% in the thoracotomy group and 96% in the sternotomy group (p =
      0.3). Five of 7 patients who presented with a significant stenosis at the first
      coronary angiography had a normal angiogram at the reangiography. None of the
      patients with nonsignificant stenosis at the early coronary angiography had any
      clinical signs of ischemia or chest pain. CONCLUSIONS: In our experience,
      anterior minithoracotomy and median sternotomy are different and distinguishable
      regarding early outcome and early graft patency. Most of the stenoses visualized
      at the early coronary angiography had vanished at a later coronary angiography,
      which makes the interpretation of the angiogram hazardous as a tool for the
      decision for redo procedure in the early postoperative period.

PMID- 10921685
TI  - The LAST operation is safe and effective: MIDCABG clinical and angiographic
      evaluation.
AB  - BACKGROUND: The aim of this study was to prospectively evaluate the angiographic
      results of a cohort of consecutive patients who underwent minimally invasive
      coronary artery revascularization. METHODS: From May 1997 to December 1998, 150
      consecutive patients underwent left internal mammary artery to left anterior
      descending artery anastomosis through a left minithoracotomy on a beating heart
      in the Cardiovascular Department of Cliniche Gavazzeni, Bergamo, Italy. The mean
      age was 61.6 years (range, 36 to 84 years); 121 patients (81%) were men. Isolated
      left anterior descending artery disease was present in 74 patients. RESULTS: In
      hospital patency was observed in 100% of the 149 angiographically controlled
      patients with no anomalies in 99.3% of the anastomoses. Anastomosis was performed
      on a diseased tract of the target vessel in 3 patients and a stenosis of the
      target vessel beyond the anastomosis was documented in 3 patients. In one case
      early angiographic control was not performed due to death of the patient on the
      1st postoperative day. The morbidity included postoperative bleeding that
      required reopening (3.3%) and intraoperative myocardial infarction (2%).
      CONCLUSIONS: A left internal mammary artery to left anterior descending artery
      anastomosis on a beating heart through a left minithoracotomy is an alternative
      approach to myocardial revascularization. Surgical invasiveness is limited,
      cardiopulmonary bypass risks are avoided, and the procedure is safe and
      effective. In our consecutive series, postoperative angiographic controls
      demonstrated graft patency in all patients and very high quality anastomoses.
      Midterm clinical follow-up (14 months) appears favorable.

PMID- 10921687
TI  - Trends in coronary artery bypass surgery results: a recent, 9-year study.
AB  - BACKGROUND: The demographics of patients undergoing coronary artery bypass
      grafting (CABG) have changed over time and may contribute to differing operative
      mortality and the combination of mortality and morbidity (M + M). In this study,
      the trends in results are analyzed and causes are suggested. METHODS:
      Prospectively collected data concerning 4,839 CABG operations was divided into
      three time cohorts (1990 to 1992, 1993 to 1995, 1996 to 1998) and analyzed by
      univariate and multivariate techniques. RESULTS: Mean age and female gender
      frequency increased in the later time cohorts (60.7 +/- 9.0 to 63.4 +/- 9.9 years
      and 16.5% to 21.4%, respectively). The following comorbidities were more
      prevalent in the later time cohorts: diabetes (26.7% versus 18.6%), renal failure
      (8.5% versus 2.2%), peripheral vascular disease (20.7% versus 11.0%), previous
      cerebrovascular accident (6.7% versus 5.0%), urgent procedures (41.5% versus
      26.9%), unstable angina (47.8% versus 31.7%), urgent CABG following myocardial
      infarction (17.1% versus 7.3%), previous percutaneous transluminal coronary
      angioplasty (8.0% versus 4.5%), ejection fraction less than 35% (20.5% versus
      10.4%), (all p < 0.05). Procedurally, increased utilization of the left internal
      mammary artery, multiple arterial conduits, and warm blood cardioplegia occurred
      in the later cohorts (91.2%, 22.2%, and 80.4% versus 78.7%, 3.4%, and 38.0%,
      respectively). The mortality rate was 2.0% and the M + M rate was 15.6% in all
      4,839 patients. The mortality and M + M for the three cohorts were 1.6%, 2.0%,
      and 2.3% and 18.4%, 17.2% and 12.5%, respectively. The risk-adjusted mortality
      and M + M decreased from 2.4% and 15.9%, respectively, in 1990 to 1992 to 1.8%
      and 8.4% in 1996 to 1998 (p < 0.001). The difference in adjusted event rates was
      minimized when the surgical factors were entered into the model. CONCLUSIONS:
      Over time, there has been a trend toward operating on older patients with more
      comorbidities. Though hospital mortality has been stable, risk-adjusted M + M has
      been in a constant decline. This decline was associated with an increased use of
      left internal mammary artery grafts, multiple arterial conduits, and warm blood
      cardioplegia during the later years of the study.

PMID- 10921688
TI  - Coronary artery bypass grafting in the conscious patient without endotracheal
      general anesthesia.
AB  - BACKGROUND: Over the past several years, considerable experience has accumulated
      in performing coronary anastomoses on the beating heart, and various aspects of
      minimally invasive approaches have been simplified. In an attempt to further
      simplify and decrease the "invasiveness" of this procedure, performing this
      operation without endotracheal general anesthesia was deemed feasible in certain
      subsets of patients. METHODS: Between October 1998 and June 1999, 5 patients
      underwent coronary artery bypass grafting without endotracheal general
      anesthesia, using high thoracic epidural block to construct extension grafts with
      a short segment of radial artery, between the in situ left or right internal
      thoracic arteries and the left anterior descending (n = 4) or right coronary
      arteries (n = 1). There were 2 female and 3 male patients, with a mean age of
      67.4 +/- 8.3 years. RESULTS: The perioperative course of the patients was
      uneventful. There was no perioperative morbidity or mortality. No patient was
      converted to general anesthesia or to conventional operation. Control angiograms
      revealed patent anastomoses in all patients. In 1 patient, spasm of the radial
      artery graft was observed that was relieved 3 weeks later spontaneously. Mean
      length of hospital stay was 2.2 +/- 0.4 days. All patients were symptom free and
      returned to normal daily life at the first postoperative month. CONCLUSIONS: Our
      initial experience confirms the feasibility of performing coronary bypass
      grafting in the conscious patient without endotracheal general anesthesia.

PMID- 10921689
TI  - Ten-year experience with Mersilene-reinforced sternal wound closure.
AB  - BACKGROUND: We were interested in reviewing our experience with Mersilene
      reinforced sternal wound closure to evaluate its overall morbidity and its impact
      on patient management. METHODS: We reviewed our experience with 1,039 patients
      undergoing median sternotomy with Mersilene-reinforced sternal wound closure over
      the past 10 years. Major wound complications, which were categorized into two
      groups, required in-hospital management and operative intervention. Group 1 had a
      sternal dehiscence alone. Group II had a major sternal infection or
      mediastinitis. RESULTS: The incidence of wound morbidity was 2.4% (n = 25). There
      were 6 (0.58%) sternal dehiscences (Group I) and 19 (1.8%) sternal wound
      infections (Group II). Patients taken to the operating room for repair of their
      sternal dehiscence or sternal infection were noted to have two completely intact
      sternal halves. CONCLUSIONS: While wound related morbidity with Mersilene tape
      closure is equivalent to the historical results of conventional wire closure,
      dehiscence occurs in a more controlled fashion with less bony destruction. The
      reduction in tissue damage associated with sternal wound dehiscence and sternal
      infection after Mersilene-reinforced sternal wound closure makes treatment of
      these potentially devastating complications easier and more efficient.

PMID- 10921690
TI  - Results of the double switch operation in the current era.
AB  - BACKGROUND: In patients with atrioventricular and arterioventricular discordance
      congenitally corrected transposition, the morphologically right ventricle may
      progressively deteriorate while functioning in the systemic circuit. The double
      switch operation has been proposed to limit this functional deterioration.
      METHODS: From October 1993 to August 1998, the records of 27 patients with
      congenitally corrected transposition were reviewed. Age at operation ranged from
      3 months to 55 years. Associated defects included ventricular septal defects in
      18, pulmonary atresia in 7, and pulmonary stenosis in 11 patients. Twenty-two
      patients had double switch operations (10 arterial switch plus Senning procedures
      and 12 Rastelli plus Senning procedures). Five patients were not candidates for
      the double switch. Before the double switch, 6 patients required pulmonary artery
      banding and 10 had functioning systemic to pulmonary artery or cavopulmonary
      shunts. RESULTS: There was no early or late mortality. Two patients required
      pacemaker implantation, both later regained normal sinus rhythm. Tricuspid valve
      function improved in all patients except one. Moderate left ventricular
      dysfunction developed 5 months postoperatively in 1 patient. CONCLUSIONS: The
      double switch operation can be performed in selected patients with minimal early
      morbidity and mortality. Longer follow-up is necessary to determine whether this
      complex approach is indeed warranted.

PMID- 10921691
TI  - Repair of isolated multiple muscular ventricular septal defects: the septal
      obliteration technique.
AB  - BACKGROUND: Isolated multiple ventricular septal defects (mVSDs) remain a
      surgical challenge. The dilemma of whether to perform a complete repair
      ultimately rests with the surgeon, who must decide if all significant septal
      defects can be located. Avoidance of a pulmonary arterial band (as part of a two
      stage repair) will negate the need for future pulmonary arterial reconstruction
      and will reduce the incidence of late right ventricular diastolic dysfunction.
      METHODS: We performed a retrospective analysis of hospital and echocardiographic
      data of eight children who underwent a septal obliteration technique (SOT) as
      part of their correction of mVSDs (with and without coarctation of the aorta).
      RESULTS: Eight children with a mean age of 10.5 months (range 1.5 to 36 months),
      and weight of 6.2 kg (range 2.1 to 13.5 kg), respectively, underwent correction
      of mVSDs. All had a single, large, perimembranous defect, additional VSDs within
      the muscular trabecular septum (juxtaposed to the moderator band), and apical
      mVSDs. All VSDs were repaired via the right atrium, with avoidance of either a
      right or left ventriculotomy. The posterior and apical defects were excluded from
      the right ventricular cavity with a pericardial patch (SOT). The follow-up period
      remains limited to a mean of 20.9 months (8 to 39 months). Two children repaired
      with SOT had previous pulmonary artery bands (neonatal coarctation repair). All
      children were successfully discharged home with a mean postoperative Qp:Qs of
      1.09:1. One pacemaker was required, but this child has since reverted back to
      normal sinus rythm. CONCLUSIONS: Our initial experience using the SOT in the
      treatment of apical VSDs as a component of isolated mVSDs has been rewarding. All
      children are currently alive, in normal sinus rhythm, and have no residual
      significant left-to-right shunts.

PMID- 10921692
TI  - Ectopia cordis and other midline defects.
AB  - BACKGROUND: Thoracic ectopia cordis and other midline defects are rare congenital
      anomalies that often occur with other intracardiac defects. Despite significant
      improvements in neonatal and infant cardiac surgeries, operations for
      thoracoabdominal ectopia cordis carry an extremely high mortality with only a few
      reported survivors of thoracic ectopia cordis. METHODS: The clinical charts of 4
      patients with ectopia cordis over a 6-year period were reviewed. Three of the
      patients showed varying degrees of Cantrell's Pentalogy; thoracic ectopia cordis
      was found in 1. We have reviewed our surgical strategies and reported the
      patients' clinical outcomes. RESULTS: All 4 patients are alive at follow-up. Two
      infants with double-outlet right ventricle have been fully corrected, and
      extracorporeal membrane oxygenation was necessary in 1 infant for cardiac failure
      following the cardiac repair. A newborn with thoracoabdominal ectopia cordis
      underwent primary repair of his diaphragmatic defect, and a silo was used to
      progressively reduce the omphalocele. He is currently awaiting elective repair of
      tetralogy of Fallot. Lastly, the patient with thoracic ectopia cordis underwent
      successful soft tissue coverage, and she is being followed in the clinic with
      restrictive muscular ventricular septal defects and a left ventricular
      diverticulum. CONCLUSIONS: Our experience along with other reports in the
      literature demonstrates that patients with thoracic and thoracoabdominal ectopia
      cordis can undergo and survive full cardiac, neurologic, and abdominal repair
      during infancy. Furthermore we advocate different approaches determined by the
      severity of the presentation and the presence of other complicating factors.

PMID- 10921693
TI  - Minimal access approach for the repair of atrial septal defect: the initial 135
      patients.
AB  - BACKGROUND: From May 1996 to August 1998 a minimal access approach was used for
      135 of 200 consecutive surgical atrial septal defects closures in children
      through young adults ranging in age from 6 months to 25 years (median 5 years).
      METHODS: A 3.5- to 5-cm midline incision was centered over the xiphoid with
      division of the xiphoid alone (transxiphoid) or of the lower sternum
      (ministernotomy); both groups underwent bicaval venous cannulation through the
      incision. Cardioplegia and aortic cross-clamping were administered through the
      incision. Cephalad retraction of the sternum with a fixed-arm retractor aided
      exposure. RESULTS: There have been no early or late deaths and no bleeding or
      wound complications. No procedure required conversion to a full sternotomy, and
      no cannulation attempt was abandoned for an alternate site. Cross-clamp and
      cardiopulmonary bypass times were equivalent to those in the full sternotomy
      group. The mean length of hospital stay in the ministernotomy group was 2.7 days.
      CONCLUSIONS: The closure of atrial septal defects can be performed through a
      transxiphoid or ministernotomy approach, conferring a satisfactory cosmetic
      result without compromising the safety or accuracy of the repair.

PMID- 10921694
TI  - Coronary to pulmonary artery collaterals in patients with pulmonary atresia and
      ventricular septal defect.
AB  - BACKGROUND: The frequency, distribution, and surgical importance of coronary
      artery to pulmonary artery (CAPA) collaterals have not been established. The aim
      of this study was to establish prevalence, anatomical pattern, and significance
      of CAPA in patients with pulmonary atresia and ventricular septal defect
      (PA/VSD). METHODS: We reviewed cardiac catheterization and operative data of 87
      consecutive, unselected patients who underwent one-stage complete unifocalization
      for PA/VSD and assessed major systemic to pulmonary collaterals from July 1992 to
      June 1998. RESULTS: CAPA collaterals were diagnosed in 9 of 87 patients (10%).
      The collaterals originated from the left coronary artery system in 7 patients and
      the right in 2. Collaterals from the left coronary system arose from the left
      main coronary artery in 3 patients and the circumflex in 4. All collaterals
      joined the central pulmonary artery, which bifurcated and supplied both lungs.
      One collateral from the right coronary system joined the stump of the main
      pulmonary artery and the other gave origin to a true left pulmonary artery, which
      was the sole supply to 75% of the left lung. Coronary artery enlargement was seen
      in 2 patients only. No patient had evidence of myocardial ischemia. Coronary
      collaterals comprised a dual source of pulmonary blood flow in all but 1 patient.
      During unifocalization, the CAPA collaterals were ligated at its origin in all
      cases, and the collateral from the right coronary to the left pulmonary artery
      was unifocalized. CONCLUSIONS: The prevalence of CAPA collaterals in patients
      with PA/VSD is approximately 10%. The diagnosis may be missed without appropriate
      angiograms. We recommend selective ascending aortogram or selective coronary
      angiogram in all patients.

PMID- 10921695
TI  - Double-chambered right ventricle presenting in adulthood.
AB  - BACKGROUND: Double-chambered right ventricle is a form of right ventricular
      outflow tract obstruction that develops over time, often in patients with an
      abnormally short distance between the moderator band and pulmonary valve. This
      lesion typically presents in childhood or adolescence and is often accompanied by
      a ventricular septal defect. Only a handful of previous cases have been described
      in which double-chambered right ventricle occurred in adulthood. METHODS: Since
      1992, three patients more than 30 years old (38, 43, and 66 years of age) have
      presented at our institution with unusual symptoms or a previous incorrect
      diagnosis. We reviewed the clinical data in these patients. RESULTS: Presenting
      symptoms included syncope, angina, and severe dyspnea resembling pulmonary
      hypertension. In 1 patient, disease was categorized as New York Heart Association
      class IV, and in the other 2 as class III. Coexisting anomalies included a patent
      foramen ovale or secundum atrial septal defect in 2 patients, a small ventricular
      septal defect in 1 (with a probable history of ventricular septal defect in
      another), and mild aortic regurgitation in 1. All patients required urgent or
      emergent operations, with peak pressures in the proximal right ventricular
      chamber of 135 to 180 mm Hg and severely depressed left ventricular function in 1
      patient. Resection of the anomalous right ventricular muscle bundles was achieved
      through a right atrial approach in all patients. All patients were alive with
      improved functional status at follow-up, which was between 15 and 40 months.
      CONCLUSIONS: Right ventricular outflow tract obstruction resulting from a double
      chambered right ventricle is rare in adults, but when it does occur it can
      present with unusual symptoms. When evaluating the patient with signs or symptoms
      of primary right heart failure, cardiologists should make an effort to image the
      entire right heart complex. Subcostal echocardiography can facilitate adequate
      visualization of the right ventricle when it is difficult to distinguish the
      subpulmonary outflow tract from the parasternal and apical windows.

PMID- 10921696
TI  - Urgency of operation in infracardiac total anomalous pulmonary venous connection.
AB  - BACKGROUND: Because the tendency for pulmonary venous obstruction in the
      infracardiac type of total anomalous pulmonary venous connection may be partially
      dependent on the connection of the descending vein to the portal vein, the
      inferior vena cava, or one of their tributary vessels, we reviewed our surgical
      experience with various subtypes of infracardiac total anomalous pulmonary venous
      connection. METHODS: The urgency of operation in 4 neonates with infracardiac
      total anomalous pulmonary venous connection was reviewed. RESULTS: Two patients
      with pulmonary venous obstruction in whom the descending vein connected to the
      portal vein were operated on immediately with successful outcome. One patient who
      had become critically ill after the ductus venosus had closed died before
      operation could be undertaken. One patient in whom the descending vein connected
      to the left hepatic vein was operated on electively with successful outcome.
      CONCLUSIONS: In hemodynamically stable patients with no clinical or
      echocardiographic signs of pulmonary venous obstruction, some form of
      differentiation with regard to urgency of operation may be appropriate. When the
      descending vein connects to the inferior vena cava or a hepatic vein, the
      operation may be performed on a semi-elective basis. In contrast, when the
      descending vein connects to the portal vein or the ductus venosus, operation
      should generally not be delayed because of the high likelihood of obstruction.

PMID- 10921698
TI  - Tissue engineering of heart valves: in vitro experiences.
AB  - BACKGROUND: Tissue engineering is a new approach, whereby techniques are being
      developed to transplant autologous cells onto biodegradable scaffolds to
      ultimately form new functional tissue in vitro and in vivo. Our laboratory has
      focused on the tissue engineering of heart valves, and we have fabricated a
      trileaflet heart valve scaffold from a biodegradable polymer, a
      polyhydroxyalkanoate. In this experiment we evaluated the suitability of this
      scaffold material as well as in vitro conditioning to create viable tissue for
      tissue engineering of a trileaflet heart valve. METHODS: We constructed a
      biodegradable and biocompatible trileaflet heart valve scaffold from a porous
      polyhydroxyalkanoate (Meatabolix Inc, Cambridge, MA). The scaffold consisted of a
      cylindrical stent (1 x 15 x 20 mm inner diameter) and leaflets (0.3 mm thick),
      which were attached to the stent by thermal processing techniques. The porous
      heart valve scaffold (pore size 100 to 240 microm) was seeded with vascular cells
      grown and expanded from an ovine carotid artery and placed into a pulsatile flow
      bioreactor for 1, 4, and 8 days. Analysis of the engineered tissue included
      biochemical examination, enviromental scanning electron microscopy, and
      histology. RESULTS: It was possible to create a trileaflet heart valve scaffold
      from polyhydroxyalkanoate, which opened and closed synchronously in a pulsatile
      flow bioreactor. The cells grew into the pores and formed a confluent layer after
      incubation and pulsatile flow exposure. The cells were mostly viable and formed
      connective tissue between the inside and the outside of the porous heart valve
      scaffold. Additionally, we demonstrated cell proliferation (DNA assay) and the
      capacity to generate collagen as measured by hydroxyproline assay and movat
      stained glycosaminoglycans under in vitro pulsatile flow conditions. CONCLUSIONS:
      Polyhydroxyalkanoates can be used to fabricate a porous, biodegradable heart
      valve scaffold. The cells appear to be viable and extracellular matrix formation
      was induced after pulsatile flow exposure.

PMID- 10921697
TI  - Mixed hematopoietic chimerism induces long-term tolerance to cardiac allografts
      in miniature swine.
AB  - BACKGROUND: Tolerance to cardiac allografts has not been achieved in large
      animals using methods that are readily applicable to human recipients. We
      investigated the effects of mixed hematopoietic chimerism on cardiac allograft
      survival and chronic rejection in miniature swine METHODS: Recipients were T-cell
      depleted using a porcine CD3 immunotoxin, and each received either of two
      nonmyeloablative preparative regimens previously demonstrated to permit the
      establishment of stable mixed hematopoietic chimerism across MHC-matched, minor
      antigen-mismatched histocompatibility barriers. Five to 12 months after the
      chimerism was induced, hearts from the original cell donors were heterotopically
      transplanted into the stable mixed chimeras. RESULTS: Cardiac allografts
      transplanted into untreated recipients across similar minor antigen barriers were
      rejected within 44 days (within 21, 28, 35, 39, 44 days among individual study
      subjects). In contrast, hearts transplanted into the mixed chimeras were all
      accepted long term ( > 153, > 225, > 286, > 362 days) without immunosuppressive
      drugs and developed minimal vasculopathy. CONCLUSIONS: Mixed hematopoietic
      chimerism, established in miniature swine using clinically relevant, non
      myeloablative conditioning regimens, permits long-term cardiac allograft survival
      without chronic immunosuppressive therapy, significant vasculopathy, or graft
      versus-host disease.

PMID- 10921699
TI  - Glucose-insulin-potassium solutions improve outcomes in diabetics who have
      coronary artery operations.
AB  - BACKGROUND: This study was undertaken to determine whether glucose-insulin
      potassium (GIK) would improve myocardial performance and limit morbidity after
      coronary artery bypass grafting in diabetic patients. METHODS: Forty consecutive
      coronary artery bypass grafting patients with medically treated diabetes mellitus
      were prospectively randomly assigned to either a GIK group (n = 20; 500 mL D5W +
      80 U regular insulin + 40 mEq KCl 30 mL/hour) or a no-GIK group (n = 20; D5W at
      30 mL/hour). The GIK was begun at anesthetic induction and continued for 12 hours
      postoperatively. RESULTS: Patients treated with GIK had higher postoperative
      cardiac indices (2.88 +/- 0.50 versus 2.20 +/- 0.39 L/minute per square meter; p
      < 0.0001), lower inotrope scores (0.40 +/- 0.68 versus 1.25 +/- 1.44; p = 0.05),
      less weight gain (5.80 +/- 3.76 versus 13.85 +/- 6.52 pounds; p < 0.0001), and
      had shorter times of ventilator support (8.35 +/- 2.60 versus 13.45 +/- 7.33
      hours; p = 0.0128). They had a significantly lower prevalence of atrial
      fibrillation (15% versus 60%; p = 0.003), and shorter hospital stays (6.70 +/-
      1.52 versus 10.15 +/- 6.62 days; p = 0.02). CONCLUSIONS: Substrate enhancement
      with GIK in diabetic patients improved myocardial performance and resulted in
      faster recovery after coronary artery bypass grafting.

PMID- 10921700
TI  - Prophylaxis of supraventricular and ventricular arrhythmias after coronary artery
      bypass grafting with low-dose sotalol.
AB  - BACKGROUND: Supraventricular tachyarrhythmia (SVT) commonly occurs shortly after
      coronary artery bypass grafting (CABG), but ventricular arrhythmias are less
      documented. METHODS: On the 1st postoperative day, 206 consecutive eligible
      patients were prospectively randomized to a sotalol group (80 mg b.i.d.; n = 103)
      or a control group without beta-blockade or antiarrhythmic drugs (n = 103).
      RESULTS: The SVT incidence (predominantly atrial fibrillation) accounted for 16%
      in the sotalol group versus 48% (p < 0.00001). Multivariate analysis showed that
      sotalol reduced the SVT incidence (p < 0.00001, odds ratio, 0.20; 95% confidence
      interval, 0.09 to 0.42), whereas a lower preoperative left ventricular ejection
      fraction (p = 0.019) and older age (p = 0.031) were independent risk factors of
      SVT occurrence. The Holter electrocardiographic analysis (24 hours) demonstrated
      that sotalol (32 versus 92; p = 0.031) decreased the median number of ventricular
      events, mostly isolated premature ventricular beats. Neither ventricular
      proarrhythmia effect nor "torsades de pointes" were detected. Despite strict
      hemodynamic-based selection, sotalol had to be discontinued in 8 patients (7.8%),
      for reasons related to asthma in 3 or cardiac reasons in 5. CONCLUSIONS: Oral low
      dose sotalol provided considerable and reliable protection in selected
      nondepressed cardiac function patients, reducing the occurrence of both
      supraventricular and ventricular arrhythmias after CABG.

PMID- 10921701
TI  - Intravenous amiodarone for prevention of atrial fibrillation after coronary
      artery bypass grafting.
AB  - BACKGROUND: Atrial fibrillation occurs in 10% to 40% of patients who undergo
      coronary artery bypass grafting. This prospective study assesses the safety and
      efficacy of low-dose intravenous amiodarone in the prevention of atrial
      fibrillation after coronary artery bypass grafting. METHODS: One hundred forty
      patients were randomly divided into two groups: an amiodarone group (n = 74)
      receiving intravenous amiadarone in a loading dose of 150 mg and maintenance dose
      of 0.4 mg x kg(-1) x h(-1) for 3 days before and 5 days after operation and a
      control group (n = 76) receiving matching infusions of 5% glucose solution.
      RESULTS: Atrial fibrillation occurred in 9 (12%) of the amiodarone group patients
      and in 26 (34%) of the control group patients during hospitalization (p < 0.01).
      The maximum ventricular rate during atrial fibrillation was significantly slower
      in the amiodarone group (107 +/- 21) than in the control group (138 +/- 24 beats
      per minute, p < 0.01). The duration of atrial fibrillation in the amiodarone
      group (1.1 +/- 1.2 hours) was significantly shorter than that in the control
      group (3.2 +/- 1.3 hours, p = 0.01). The two groups had no significant
      differences in incidence of major morbidity (8 of 74 versus 8 of 76 in amiodarone
      and control groups, respectively) or mortality (4 of 74 versus 5 of 76). However,
      the control group had significantly longer intensive care unit stays (132 +/- 24
      versus 111 +/- 19 hours, p < 0.01). CONCLUSIONS: Perioperative low-dose
      intravenous amiodarone significantly reduces the incidence, ventricular rate, and
      duration of atrial fibrillation after coronary artery bypass grafting.
      Furthermore, low-dose intravenous amiodarone is well tolerated and does not
      increase the risk of intraoperative or postoperative complications.

PMID- 10921702
TI  - Predictive accuracy study: comparing a statistical model to clinicians' estimates
      of outcomes after coronary bypass surgery.
AB  - BACKGROUND: The purpose of this study was to compare clinicians' prior
      probability estimates of operative mortality (OM) and prolonged intensive care
      unit stay (ICU) length of stay greater than 48 hours after coronary artery bypass
      graft surgery (CABG) with estimates derived from statistical models alone.
      METHODS: Nine clinicians estimated the predicted probability of OM and ICU stay
      greater than 48 hours from an abstract of information for each of 100 patients
      selected from the 1996 to 1997 database of 1,904 patients who underwent isolated
      CABG. Logistic regression models were used to calculate the predicted probability
      of OM and ICU stay greater than 48 hours for each patient. The study sample was
      split into two parts; clinicians were randomly given access to a predictive rule
      to guide their judgements for one part of the study. RESULTS: Clinicians'
      estimates were similar with or without access to the rule, and both parts of the
      study were therefore pooled. Clinicians significantly overestimated the
      probability of OM (model 6.3% +/- 1%, clinicians 7.6% +/- 3%, p = 0.0001) and ICU
      stay greater than 48 hours (model 25% +/- 2%, clinicians 28% +/- 1%, p = 0.0012).
      Clinicians' estimates of OM were not significantly higher than the model's for
      nonsurvivors (0.8% +/- 0.7%, p = 0.2), but were significantly higher for
      survivors (1.4% +/- 0.3%, p = 0.039). CONCLUSIONS: Clinicians trusted their own
      empiric estimates rather than a predictive rule and overestimated the probability
      of OM and ICU stay greater than 48 hours.

PMID- 10921703
TI  - Predictors of 30-day hospital readmission after coronary artery bypass.
AB  - BACKGROUND: Risk factors for 30-day hospital readmission following coronary
      artery bypass grafting (CABG) have not been established. METHODS: We
      prospectively followed 485 consecutive patients who underwent isolated primary
      CABG at our institution in 1997. Patients were contacted by telephone at 30 days
      following operation to determine readmission status. RESULTS: The overall
      readmission rate was 16% (76 of 485). Female gender (25% versus 11%, p = 0.001)
      and diabetes (22% versus 12%, p = 0.005) were associated with significantly
      higher readmission rates. The relationship between female gender and readmission
      persisted after correcting for age and other comorbidities. Congestive heart
      failure trended towards a significant relationship with increased readmission
      rate (22% versus 14%, p = 0.09). There were no significant associations between
      30-day readmission rate and age, hypertension, chronic obstructive pulmonary
      disease, history of myocardial infarction, peripheral vascular disease,
      creatinine level of > or = 1.4 mg/dL, or decreased left ventricular ejection
      fraction (< 40%). CONCLUSIONS: These data show that most of the classic risk
      factors for postoperative mortality are not necessarily associated with increased
      readmission. However, female gender and diabetes are associated with greater than
      twice the risk of 30-day readmission following CABG.

PMID- 10921704
TI  - Association between postoperative hypothermia and adverse outcome after coronary
      artery bypass surgery.
AB  - BACKGROUND: We examined the effect on outcome of mild hypothermia (< 36 degrees
      C) upon intensive care unit (ICU) admission on patient outcome after coronary
      artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: We
      performed a retrospective database analysis of 5,701 isolated CABG patients
      requiring CPB, operated upon from January 1995 to June 1997. Patients were
      classified as either hypo- (< 36 degrees C) or normothermic (> or = 36 degrees C)
      upon ICU admission. ICU admission bladder core temperature (BCT) versus outcome
      was evaluated. Outcome measures included mortality, resource utilization
      (mechanical ventilation time, ICU and hospital length of stay, and postoperative
      packed red blood cell transfusion), and major morbidity (cardiac, renal,
      neurologic, or major infection). RESULTS: Overall, patients admitted to the ICU
      with BCT < 36 degrees C had a significantly greater mortality (p = 0.02),
      prolonged mechanical ventilation (p = 0.007), packed red blood cell transfusion
      (p = 0.001), ICU (p = 0.01), and hospital (p = 0.005) length of stay.
      CONCLUSIONS: BCT of less than 36 degrees C, upon ICU admission, has a significant
      association with adverse outcome after CABG with CPB. M An __ Tl QA_7_t-0

PMID- 10921705
TI  - Marginal cost of liberating ventilator-dependent patients after cardiac surgery
      in a stepdown unit.
AB  - BACKGROUND: With the recent changes in Medicare reimbursement for ventilator
      dependent patients at skilled nursing facilities, hospitals may, by necessity, be
      required to liberate these patients from mechanical ventilation before discharge.
      This study sought to determine the marginal cost of liberating ventilator
      dependent patients in a cardiac stepdown unit. METHODS: By retrospective
      analysis, the complete billing records of all 15 ventilator-dependent patients
      were obtained and abstracted for each item used. The drug or supply acquisition
      cost and direct variable cost of other items and labor were used to compute the
      daily and total marginal cost for each patient. RESULTS: Of 15 patients, 13 were
      discharged alive and liberated from mechanical ventilation. Length of stay was 28
      +/- 23 days. Average per diem cost was $438.77 +/- 152.34. Costs were
      significantly higher in patients who required hemodialysis: $555.31 +/- 491.04
      versus $380.54 +/- 272.25 (p < 0.01). CONCLUSIONS: Ventilator-dependent patients
      can be inexpensively liberated from mechanical ventilation in a stepdown unit.

PMID- 10921706
TI  - Reduction of heparin dose is not beneficial to platelet function.
AB  - BACKGROUND: To clarify the effects of the reduction of heparin dose on platelets,
      we conducted a prospective trial on patients undergoing cardiopulmonary bypass.
      METHODS: Twenty-three patients undergoing coronary artery bypass grafting were
      studied. The systemic heparin dose was 300 IU/kg in the control group (n = 11)
      and 200 IU/kg in the low-dose group (n = 12). Heparin-coated cardiopulmonary
      bypass equipment was used for both the groups. Platelet counts, beta
      thromboglobulin (beta-TG) and platelet factor 4 (PF4) concentrations were
      measured and the arterial filters in the circuits were observed by electron
      microscopy. RESULTS: Platelet counts were higher in the low-dose group than in
      the control group (p < 0.01). No significant differences were found in the
      platelet release reaction (beta-TG and PF4). Electron microscopy demonstrated
      that cell adhesion on the arterial filters in the control group was significantly
      more marked than in the low-dose group (p < 0.01) and that most of the cells on
      the filters were neutrophils. CONCLUSIONS: We conclude that the reduction of
      heparin dose with the use of heparin-coated equipment reduces platelet loss, but
      does not suppress the platelet release reaction. Furthermore, the reduction of
      heparin dose reduces adherence of leukocytes to the filter surface.

PMID- 10921707
TI  - Impact of heparin bonding on pediatric cardiopulmonary bypass: a prospective
      randomized study.
AB  - BACKGROUND: Heparin-coated circuits reduce the inflammatory response to
      cardiopulmonary bypass in adult patients; however, little is known about its
      effects in the pediatric population. Two studies were performed to assess this
      technology's impact on inflammation and clinical outcomes. METHODS: In a pilot
      study, complement and interleukins were measured in 19 patients who had either
      uncoated cardiopulmonary bypass circuits or heparin-bonded circuits.
      Subsequently, 23 additional patients were studied in a randomized fashion.
      Respiratory function and blood product utilization were recorded. RESULTS: In the
      pilot study, heparin-bonded circuit patients had less complement 3a (p < 0.001)
      and interleukin-8 (p < 0.05) compared with uncoated cardiopulmonary bypass
      circuit patients. The randomized study revealed that the heparin-bonded circuit
      was associated with reduced complement 3a (p = 0.02). Multiple variable analysis
      revealed that the following postoperative variables were increased with bypass
      time (p = 0.01) and diminished with heparin-bonded circuits: interleukins (p =
      0.01), peak airway pressures (p = 0.05), and prothrombin time (p = 0.03).
      CONCLUSIONS: Heparin-bonded circuits significantly reduce cytokines and
      complement during cardiopulmonary bypass and lower interleukin levels postbypass;
      they were also associated with improved pulmonary and coagulation function.
      Heparin-bonded circuits ameliorate the systemic inflammatory response in
      pediatric patients from cardiopulmonary bypass.

PMID- 10921708
TI  - Cardioplegia and ischemia in the canine heart evaluated by 31P magnetic resonance
      spectroscopy.
AB  - BACKGROUND: Warm continuous blood cardioplegia provides excellent protection, but
      must be interrupted by ischemic intervals to aid visualization. We hypothesized
      that (1) as ischemia is prolonged, the reduced metabolic rate offered by cooling
      gives the advantage to hypothermic cardioplegia; and (2) prior cardioplegia
      mitigates the deleterious effects of normothermic ischemia. METHODS: Isolated
      cross-perfused canine hearts underwent cardioplegic arrest followed by 45 minutes
      of global ischemia at 10 degrees C or 37 degrees C, or 45 minutes of normothermic
      ischemia without prior cardioplegia. Left ventricular function was measured at
      baseline and during 2 hours of recovery. Metabolism was continuously evaluated by
      phosphorus-31 magnetic resonance spectroscopy. RESULTS: Adenosine triphosphate
      was 71% +/- 4%, 71% +/- 7%, and 38% +/- 5% of baseline at 30 minutes, and 71% +/-
      4%, 48% +/- 5%, and 39% +/- 6% at 42 minutes of ischemia in the cold ischemia,
      warm ischemia, and normothermic ischemia without prior cardioplegia groups,
      respectively. Left ventricular systolic function, left ventricular relaxation,
      and high-energy phosphate levels recovered fully after cold cardioplegia and
      ischemia. Prior cardioplegia delayed the decline in intracellular pH during
      normothermic ischemia initially by 9 minutes, and better preserved left
      ventricular relaxation during recovery, but did not ameliorate the severe
      postischemic impairment of left ventricular systolic function, marked adenosine
      triphosphate depletion, and creatine phosphate increase. Left ventricular
      distensibility decreased in all groups. CONCLUSIONS: When cardioplegia is
      followed by prolonged ischemia, better protection is provided by hypothermia than
      by normothermia. Prior cardioplegia confers little advantage on recovery after
      prolonged normothermic ischemia but delays initial ischemic metabolic
      deterioration, which would contribute to the safety of brief interruptions of
      warm cardioplegia.

PMID- 10921709
TI  - Myocardial outflow of prostacyclin in relation to metabolic stress during off
      pump coronary artery bypass grafting.
AB  - BACKGROUND: The metabolic changes, possible myocardial damage, and influence on
      the vascular endothelium during off-pump coronary artery bypass grafting have
      been investigated. METHODS: Coronary sinus and arterial blood samples were
      obtained before coronary arterial occlusion, after 10 minutes of ischemia, and
      after 1 and 10 minutes of reperfusion in 9 patients who had an anastomosis
      performed to the left anterior descending coronary artery off-pump bypass
      RESULTS: The mean ischemic time was 14 +/- 1 minutes. The arteriovenous
      difference in lactate decreased during ischemia to reach a minimum at 1 minute of
      reperfusion (-0.15 +/- 0.06 micromol/L compared to 0.21 +/- 10 micromol/L before
      ischemia; p < 0.01). Myocardial lactate extraction decreased from 14.2 +/- 6.8
      micromol/min before ischemia to -10.9 +/- 6.5 micromol/min after 1 minute of
      reperfusion (p < 0.01). Simultaneously, the arteriovenous difference in 6-keto
      PGF(1alpha), the stable metabolite of prostacyclin, decreased from -30 +/- 26
      pg/mL to -258 +/- 80 pg/mL at 1 minute of reperfusion (p < 0.05), and the 6-keto
      PGF(1alpha) extraction over the heart decreased -556 +/- 466 pg/min to -18,560 +/
      5,683 pg/min (p < 0.01). CONCLUSIONS: The localized myocardial ischemia
      associated with these procedures causes changes in the myocardium and endothelial
      influence. Coronary bypass surgery performed on the beating heart may not be
      superior in preventing cardiac ischemia and endothelial disturbance, compared
      with conventional bypass surgery.

PMID- 10921710
TI  - Transit time flow measurement: experimental validation and comparison of three
      different systems.
AB  - BACKGROUND: Bloodflow measurements are of major clinical importance for quality
      control in vascular surgery. They allow detection of low-flow situations which
      may influence outcome adversely. The purpose of the present study was to validate
      three different flow systems for measuring absolute blood flow. METHODS:
      Measurements were performed in an experimental flow model using arteries and
      veins and blood or saline at two different temperatures. As a reference method
      true flow was measured by volume sampling. RESULTS: Correlation coefficients
      between transit time flow and true flow measurements ranged between 0.71 and
      0.92. Systematic overestimation and underestimation of transit time flow were
      observed, but after second-order correction all correlations were excellent,
      ranging from 0.93 to 0.95 irrespective of flow medium and temperature.
      CONCLUSIONS: Transit time flow measurements are exact and reproducible. Second
      order correction yields good accuracy and high precision, with minimal
      differences among the three systems evaluated.

PMID- 10921711
TI  - Assessment of patented coronary end-to-side anastomotic devices using
      micromechanical bonding.
AB  - BACKGROUND: Despite multiple patented ideas for vascular end-to-side anastomotic
      devices, and the growing need for them in minimally invasive coronary bypass
      procedures, no device has been evaluated clinically yet. This study assessed
      patents of micromechanical end-to-side anastomotic devices with respect to
      application in coronary artery bypass grafting. METHODS: Patents were categorized
      with respect to their micromechanical bonding principle. Calculated values for
      the wall strain during the construction of an anastomosis were compared with the
      allowable strain for human coronary arteries. RESULTS: From 51 patents describing
      vascular anastomotic devices, 11 ideas, categorized into four groups (staples,
      clips, mounting systems, and intraluminal stent structures), are serious
      candidates for coronary end-to-side anastomoses. Most ideas use an anvil for
      proper application of the bonding elements. For small (1.5 mm) coronary arteries,
      the calculated wall strain was 0.87, exceeding the breaking strain (0.45) in 60-
      to 79-year-old patients. CONCLUSIONS: In a coronary anastomotic device, the
      concept of using an anvil for the application of micromechanical bonding elements
      is not attractive, because excessive wall strain is likely to occur.

PMID- 10921712
TI  - Epidural versus subdural spinal cord cooling: cerebrospinal fluid temperature and
      pressure changes.
AB  - BACKGROUND: Regional spinal cord cooling can increase the tolerable duration for
      spinal cord ischemia resulting from aortic clamping. We compared the efficacy of
      epidural and subdural cooling and the effect of the resulting cerebrospinal fluid
      pressure (CSF) increases on spinal cord motor neuron function. METHODS: In 8
      pigs, CSF temperature and pressure were assessed in the subdural space at L4,
      T15, and T7. Saline was infused at 333, 666, and 999 ml/h at four consecutive
      locations: L4 subdural, L4 epidural, T15 subdural, and T15 epidural. First, the
      influence of CSF-pressure increases during normothermic infusion on transcranial
      motor evoked potentials (tc-MEPs) was assessed. Then, hypothermic infusion (4
      degrees C) was performed to assess CSF-temperature changes. RESULTS: During
      normothermic infusion, baseline CSF pressures increased uniformly from 6 +/- 4 mm
      Hg to 34 +/- 18, 42 +/- 17, and 50 +/- 18 mm Hg with increasing infusion rates (p
      < 0.001), and did not differ between epidural or subdural infusion. Tc-MEPs
      indicated spinal cord ischemia in 6 animals when CSF pressures reached 65 +/- 11
      mm Hg. During hypothermic infusion, CSF temperatures decreased from 37 degrees to
      35 +/- 1.2 degrees, 31 +/- 2.2 degrees, and 28 +/- 2.8 degrees C, but increasing
      CSF-temperature gradients were observed between the infusion location and distant
      segments. Subdural cooling resulted in lower CSF temperatures (p < 0.001), but
      caused larger CSF-pressure increases (p < 0.001). CONCLUSIONS: Subdural and
      epidural infusion cooling produce localized spinal cord hypothermia in pigs. The
      concurrent pressure increases, however, are uniformly distributed and can result
      in tc-MEP evidence of ischemia.

PMID- 10921713
TI  - Inhibition of needlestick-induced simulated viremia by local measures.
AB  - BACKGROUND: The possibility of confinement of simulated retrovirus to the
      inoculation site after needlestick injuries to enhance chances of local
      intervention and function of lymphaticovenous communications was investigated.
      METHODS: Using the canine model, technetium-99 m sulfur colloid particles were
      injected subcutaneously and into the vein and lymphatics. Blood and lymph were
      collected at a higher level from the femoral vein and the major lymphatic. Flow
      rates, particle arrival times, concentrations, and other variables were evaluated
      for 45 minutes by gamma counting. A tourniquet was used to slow dissemination
      after subcutaneous injection. RESULTS: After subcutaneous inoculation, particles
      arrived in the blood at 2.81 +/- 0.54 minutes and in the lymph at 6.0 +/- 1.47
      minutes. Application of a tourniquet delayed appearance in the blood to 7.11 +/-
      1.5 minutes and in the lymph to 40.0 +/- 5.1 minutes. Concentration of particles
      in lymph was 1,000 times higher than in the blood. Flux values were comparable in
      both pathways, but accumulation patterns were different. After intravenous
      injection, particles arrived in lymph at 25.4 +/- 6.44 minutes. After
      intralymphatic injection particles arrived in the blood within 4 seconds.
      CONCLUSIONS: There are functional lymphaticovenous communications at the
      peripheral level. The period between virus inoculation and blood and lymph
      invasion may be extended by application of a tourniquet; therefore, time could be
      gained for local intervention.

PMID- 10921714
TI  - Lobectomy with tangential pulmonary artery resection without regard to pulmonary
      function.
AB  - BACKGROUND: Non-small cell carcinoma of the lung invading the pulmonary artery
      (PA) has traditionally been treated by pneumonectomy. Although PA resection and
      reconstruction (PAR) has begun to gain acceptance, previous series of PAR by the
      simplest technique of tangential excision and primary repair have been
      unfavorable. We have maintained a policy of performing PAR preferentially
      whenever anatomically feasible, and usually this has been possible by tangential
      excision and primary repair. This study sought to determine if this approach is
      sound. METHODS: Retrospective clinical and pathologic review. RESULTS: Thirty
      three PARs were performed from 1992 to 1999. The patients, followed 6 to 65
      months (mean 25), were aged 36 to 80 years (mean 61), and their tumors were
      pathologic stage IB (n = 7), IIB (n = 13), IIIA (n = 9), and IIIB (n = 4). The
      mean preoperative forced expiratory volume in 1 second was 70% predicted. The
      procedures included 14 bronchial sleeve lobectomies with PAR and 19 simple
      lobectomies with PAR. The PARs were performed without heparinization and included
      19 tangential excisions with primary closure, 11 larger tangential excisions with
      pericardial patch closure, and 3 sleeve resections. There were no operative
      deaths and 2 (6.1%) early major complications, all unrelated to the PAR. Thirteen
      patients (39%) had early minor complications. Four-year Kaplan-Meier survival was
      48.3% for stages I/II and 45% for stage III. Ipsilateral, central, intrathoracic
      recurrence occurred in 3 patients (9.1%). CONCLUSIONS: These data are not
      dramatically different from those reported for standard resections. Although the
      numbers are small, the results suggest that lobectomy with PAR by tangential
      excision is an acceptable alternative to pneumonectomy whenever anatomically
      possible.

PMID- 10921715
TI  - Needlescopic thoracic sympathectomy: treatment for palmar hyperhidrosis.
AB  - BACKGROUND: Open thoracic sympathectomy has been the established option for
      patients with essential hyperhidrosis. Recently, video-assisted endoscopic
      sympathectomy has provided a simple, safe, reliable, and cost-effective
      alternative to the earlier technique. With advances in instrumentation,
      performing the procedure through 2-mm and 3-mm needlescopic ports is now
      possible. The authors evaluate the effectiveness of so-called needlescopic
      thoracic sympathectomy for the treatment of primary hyperhidrosis. METHODS:
      Thirty five consecutive patients with a mean age of 24 years, including 23 men
      and 12 women, underwent bilateral needlescopic thoracic sympathectomies at the
      National University Hospital of Singapore. RESULTS: The mean operative duration
      was 56 minutes, and the mean hospital stay was 1.2 days. In no patient did
      Horner's syndrome or significant pneumothorax develop. The rate of success,
      defined as completely dry hands, was 97%. Two patients had unilateral recurrences
      that responded well to repeat needlescopic sympathectomies. We performed a total
      of 72 sympathectomies. CONCLUSIONS: Our study demonstrates that the use of
      miniature port access sites produces excellent medical and cosmetic results and
      is associated with a short hospital stay and low risk of complications.

PMID- 10921716
TI  - VATS lobectomy reduces cytokine responses compared with conventional surgery.
AB  - BACKGROUND: Video-assisted thoracic surgery (VATS) lobectomy for early lung
      cancer has been shown to be technically feasible. Comparative studies on
      laparoscopic versus open procedures indicate that laparoscopy may reduce
      inflammatory reactions as reflected by the lesser release of cytokines. We
      investigated the cytokine responses following VATS and conventional lobectomy for
      clinical stage I lung cancer. METHODS: Thirty-six patients with clinical stage I
      nonsmall cell lung cancer were studied. 18 patients underwent VATS lobectomy and
      the other 18 by conventional thoracotomy. There were no differences between the
      two groups with respect to age, gender, pulmonary function, smoking history,
      comorbidity, tumor size, and pathology. Plasma levels of tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, IL-8, and an antiinflammatory
      cytokine IL-10 were measured before surgery, at the end of the procedure, and 4,
      8, 24, and 48 hours thereafter in all patients. RESULTS: There was no mortality
      or major complication in either group. Analgesic requirement was significantly
      less in the VATS group. Although the release of TNF-alpha and IL-1beta were
      minimal after surgery in both groups, the levels of IL-6, IL-8, and IL-10 were
      elevated. IL-6 and IL-8 levels were significantly lower in the VATS group at the
      end of surgery than in the open group. In addition, reduced release of IL-10 was
      also observed in the VATS group shortly after surgery. CONCLUSIONS: VATS
      lobectomy is associated with reduced postoperative release of both
      proinflammatory and antiinflammatory cytokines compared with the open approach.
      The clinical significance of these findings remains to be fully elucidated.

PMID- 10921717
TI  - Role of surgical resection in broncholithiasis.
AB  - BACKGROUND: Broncholithiasis is an uncommon problem with life-threatening
      complications. The purpose of this study was to update our experience in patients
      with broncholithiasis managed by surgical intervention. METHODS: From January
      1984 to January 1998, 118 patients were diagnosed with broncholithiasis at our
      institution. We reviewed the medical records of those patients who underwent
      surgical treatment. RESULTS: There were 47 patients (19 men and 28 women). Median
      age was 58 years (range, 18 to 90 years). Indications for operation were symptoms
      in 44 patients and abnormal roentgenograms in 3 patients. Operative procedures
      included lung resection in 30 patients, broncholithectomy with or without
      bronchoplasty in 16, and segmental bronchial resection in 1 patient. There were
      no operative deaths. Postoperative complications occurred in 16 patients (34%).
      Follow-up was complete in 46 patients (98%) and ranged from 11 to 165 months
      (median, 74 months). The 15-year actuarial survival did not differ significantly
      from that of a matched control group (p = 0.774). At follow-up, 28 patients
      (68.3%) were asymptomatic. Symptoms continued in 12 patients. Recurrent or
      persistent disease was documented in 6 patients (14.6%). The site of recurrence
      was in a new location in 3 patients, a previous site in 2, and unknown in 1
      patient. Subsequent management included observation in 3 patients, bronchoscopic
      removal in 2, and bilobectomy in 1 patient. CONCLUSIONS: Surgical resection for
      broncholithiasis is an effective method of management for this disease and can be
      done with low mortality and morbidity. Progression of the disease may lead to
      recurrence and further surgical intervention.

PMID- 10921718
TI  - Long-term results after video-assisted thoracoscopic surgery for first-time and
      recurrent spontaneous pneumothorax.
AB  - BACKGROUND: Few investigators have reported on results after video-assisted
      thoracoscopic surgery (VATS) for spontaneous pneumothorax (SP) with follow-up
      periods longer than 24 months. The aim of this study was to evaluate VATS for
      first-time and recurrent SP and to follow patients long-term. METHODS: One
      hundred nine patients were followed long-term after treatment of SP by VATS.
      Ninety-five patients had primary SP and 14 had secondary SP. Sixty-two patients
      had a first episode and 47 had a recurrence. In 72 patients leaks or ruptured
      blebs were identified and excised without subsequent pleurodesis. In 37 patients
      showing no ruptured bullae or leaks only pleurodesis was applied. RESULTS: Median
      follow-up was 53.2 months. Postoperative complications were rare. Three patients
      (2.7%) had a prolonged air leak. The long-term recurrence rate was 4.6%. Only
      those patients who had not received pleurodesis at the time of first treatment by
      VATS experienced recurrence. CONCLUSIONS: Immediate postoperative results show
      VATS to be a safe and reliable method in first-time and recurrent SP to obtain
      quick reexpansion of the lung. Long-term recurrence rates are acceptable and
      compare with results after open thoracotomy. Pleurodesis should be included in
      each procedure for adequate recurrence prevention.

PMID- 10921719
TI  - Prognostic factors in neuroendocrine lung tumors: a Spanish Multicenter Study.
      Spanish Multicenter Study of Neuroendocrine Tumors of the Lung of the Spanish
      Society of Pneumonology and Thoracic Surgery (EMETNE-SEPAR).
AB  - BACKGROUND: This study examines the experience of the Spanish Multicenter Study
      of Neuroendocrine Tumors of the Lung through the clinical data and behavior of
      patients treated for this pathologic process. METHODS: From 1980 to 1997, 361
      cases of neuroendocrine carcinomas (NEC) were treated surgically. Patients were
      enrolled in a protocol using the pathologic and follow-up reports. According to
      Dreslers' criteria, the cases were segregated into grade 1 (typical carcinoid),
      grade 2 (atypical carcinoid), grade 3 large cell type, and grade 3 small cell
      type. Several variables were reviewed in all patients. Statistical analysis was
      performed to determine whether clinical characteristics and differentiation were
      associated with significant differences in the prognosis. RESULTS: A total of 261
      cases of NEC were identified with grade 1, 43 with grade 2, and with grade 3: 22
      of large and 35 of small cells. Five-year survival for different grades was as
      follows: grade 1, 96%; 2, 72%; 3 large cell type, 21%; and 3 small cell type,
      14%. When a comparative analysis between typical and atypical carcinoids was
      performed a significant difference for mean age, tumor size, nodal metastases,
      and recurrence was observed. However, female sex, nodal metastases, and
      recurrence rate differed between atypical carcinoids and grade 3 NEC of large
      cells. A difference in recurrence rate was found between patients with both types
      of grade 3 NEC. CONCLUSIONS: The progressive deterioration of tumor organization
      highlights that neuroendocrine tumors constitute a continuous spectrum. A careful
      observation of pathologic findings is necessary to individualize their prognostic
      factors.

PMID- 10921720
TI  - Effects of storage and reperfusion oxygen content on substrate metabolism in the
      isolated rat lung.
AB  - BACKGROUND: Lung transplantation requires a period of storage and ischemia; we
      examined the largely unknown effects of that period on intermediary metabolism.
      METHODS: Two groups of isolated rat lung blocks (n = 16 each) were flushed with
      Euro-Collins solution and harvested. The lung blocks were immediately ventilated
      and either perfused for 30 minutes with an erythrocyte-based solution containing
      carbon 13 labeled substrates (group 1) or stored for 6 hours at 1 degree C and
      then reperfused (group 2). Half of each group was reperfused at a physiologic Po2
      the other half at high Po2. Analysis of carbon 13 isotopomers was performed to
      determine substrate utilization through aerobic pathways in lung tissue. RESULTS:
      Lungs from both groups oxidized all major substrates. The contribution of fatty
      acids to acetylcoenzyme acid oxidized in the citric acid cycle was significantly
      higher in group 2 than in group 1 (31.3% +/- 2.2% versus 22.0% +/- 2.1%, p <
      0.05). Perfusate Po2 did not affect substrate preference. Gas exchange was worse
      in stored lungs. CONCLUSIONS: After a period of hypothermic ischemia and storage,
      substrate preference in lung tissue exhibits a switch towards fatty acids. As
      fatty acid oxidation occurring after ischemia is deleterious in other organs,
      strategies to inhibit this process in stored lungs may warrant further
      investigation.

PMID- 10921721
TI  - Postsurgical pleurodesis with autologous blood in patients with persistent air
      leak.
AB  - BACKGROUND: Persistent air leak after operation on the lung is one of the most
      common problems encountered by thoracic surgeons. We present 6 patients who
      underwent pleurodesis with autologous blood for persistent air leak after
      operation. METHODS: Between June 1993 and January 1998, pleurodesis with
      autologous blood was performed in 6 patients who had air leak of more than 10
      days' duration after operation for non-small cell lung cancer. A sample of
      peripheral blood was taken from the patient's arm and immediately introduced into
      the chest tube with no additives. The chest tube was left unclamped and off
      suction, connected to the waterseal drainage, and kept 60 cm above the patient's
      chest. The next day, the waterseal and chest roentgenogram were reviewed before
      the chest tube was removed. RESULTS: A persistent air leak with a mean duration
      of 16.7 days was observed after the initial operation. Fifty to 250 mL of blood
      was introduced one time into the chest tube. No patient experienced pain,
      respiratory difficulty, fever, or episodes of coughing during the procedure.
      After 24 hours, no air leak was detected in the waterseal drainage in any
      patient. CONCLUSIONS: On the basis of these preliminary findings, we believe
      pleurodesis with autologous blood is a safe and effective method for treating
      persistent air leak after a thoracic surgical procedure.

PMID- 10921722
TI  - Entire septal patch technique for postinfarction ventricular septal rupture.
AB  - Postinfarction ventricular septal rupture is still a surgically challenging
      situation with high operative mortality. We report a case of ventricular septal
      rupture in a 75-year-old woman successfully treated with our newly devised
      technique, in which a pliable large septal path is fixed with transmural sutures
      placed in posterior left ventricular free wall and anterior ventriculotomy
      closing sutures, thus covering the septal wall almost entirely. Our method may
      simplify the operation and reduce the risk of residual leakage.

PMID- 10921723
TI  - Surgical treatment of a chest-wall penetrating left ventricular pseudoaneurysm.
AB  - This report describes the treatment of a patient who developed a chest-wall
      penetrating pseudoaneurysm 3 years after coronary bypass grafting and after the
      resection of a lateral wall left ventricular aneurysm twice. The patient
      presented with a pulsatile tumor in the left submammilar region. Surgery was done
      in deep hypothermia, with femoro-femoral cannulation and via a left anterolateral
      thoracotomy. The perioperative course was uneventful and the patient is still
      well 5 years after surgery.

PMID- 10921724
TI  - Successful weaning of a transplanted heart from biventricular assist device.
AB  - Exceptionally few cases worldwide have survived weaning from a biventricular
      assist device following heart transplantation in contrast to those who underwent
      early retransplantation. We present a successful outcome after biventricular
      assist device implantation following initial biventricular failure after heart
      transplantation. Weaning could be performed after 1 week, although pulmonary
      vascular resistance remained markedly elevated.

PMID- 10921725
TI  - Mechanical bridge to recovery in fulminant myocarditis.
AB  - A patient with acute fulminant lymphocytic myocarditis and cardiogenic shock was
      successfully treated by mechanical off loading of the left ventricle. A
      nonpulsatile left-heart bypass was undertaken with an implantable centrifugal
      blood pump. Careful weaning resulted in device removal on the seventh day. Left
      and right ventricular function is sustained at 7 months. Widespread application
      of this method depends on the availability of an inexpensive user friendly blood
      pump, appropriate weaning protocols and emerging strategies to promote
      sustainable myocardial recovery.

PMID- 10921726
TI  - Possible relationship between degenerative cardiac valvular pathology and lyme
      disease.
AB  - We report an unusual clinical presentation of Lyme carditis in a previously
      healthy 20-year-old black woman without any epidemiologic history of Lyme
      disease, fulminant in nature, involving a heart valve necessitating emergent
      mitral valve replacement, and requiring further surgical intervention because of
      the development of pericardial effusion and tamponade. A dilated right ventricle
      with normal contractility and severe tricuspid regurgitation with increase in the
      right atrial size diagnosed later remains under close surveillance.

PMID- 10921727
TI  - Heterotopic cardiac transplantation and Batista operation.
AB  - We report the case of an infant who was first seen with dilated cardiomyopathy at
      the age of 3 1/2 months and 2 months later, successfully underwent heterotopic
      cardiac transplantation in combination with partial left ventriculectomy. The
      benefits of combining both procedures in such a young infant particularly with
      regard to containment of early graft dysfunction, reduction of respiratory
      problems, and weight mismatch are discussed.

PMID- 10921728
TI  - Strategy for pulmonary atresia and intact ventricular septum.
AB  - Pulmonary atresia with an intact ventricular septum is characterized by varying
      degrees of right ventricular cavity hypoplasia. This factor is critical in
      determining the most appropriate surgical approach for each patient. We describe
      a patient who underwent definitive biventricular surgical repair in early
      infancy. We used an atrial septal defect patch with a one-way valve and performed
      a right ventricular overhaul after a balloon valvotomy.

PMID- 10921729
TI  - Intraoperative balloon angioplasty for aortic coarctation after Norwood
      operation.
AB  - We report intraoperative balloon angioplasty for recurrent aortic coarctation in
      hypoplastic left heart syndrome. After bidirectional Glenn anastomosis, balloon
      angioplasty was performed via ascending aorta. Pressure gradient across the
      coarctation decreased from 45 to 8 mm Hg. Intravascular ultrasound revealed
      successful splits of thickened intima without any extensive dissection.
      Intraoperative balloon angioplasty is a safe and favorable procedure for
      hypoplastic left heart syndrome because balloon inflation before bidirectional
      Glenn anastomosis could induce serious ventricular collapse or arrhythmias.

PMID- 10921730
TI  - Congenital subclavian aortic steal syndrome: hypoplastic aortic arch with severe
      coarctation of the aorta of unusual location.
AB  - An unusual case of subclavian-aortic steal syndrome in a pediatric patient with
      hypoplastic aortic arch with coarctation of the aorta of unusual location is
      described. Aortography showed hypoplasia of the arcus aorta and severe
      coarctation proximal to the left subclavian artery associated with an aneurysm
      formation on the isthmus and descending aorta. The enlargement of the arcus aorta
      was accomplished by prosthetic patch aortoplasty extending from the ascending to
      descending aorta via median sternotomy using cardiopulmonary bypass and moderate
      hypothermia. Postoperatively, the patient is doing well with equalized blood
      pressure.

PMID- 10921731
TI  - Tracheobronchial glomus tumor.
AB  - Glomus tumors are uncommon. A review of the literature for tracheobronchial
      glomus tumors revealed 13 tracheal glomus tumors. The diagnosis may be elusive
      and so the true incidence of tracheobronchial glomus tumors may be greater than
      that reported. Three of the 14 glomus tumors were initially believed to be
      carcinoid. Glomus tumors should be included in the differential diagnosis of
      tracheobronchial tumors.

PMID- 10921732
TI  - Glomus tumor of the trachea.
AB  - Extracutaneous glomus tumors are unusual and their occurrence in the trachea has
      been recognized with extreme rarity. We present a case of surgically resected
      glomus tumor of the trachea in a 34-year-old man who presented with hemoptysis
      and who was initially diagnosed as having a carcinoid tumor.

PMID- 10921733
TI  - Thymic hemangioma presenting with recurrent pleural effusion.
AB  - Thymic hemangiomas are rare mediastinal tumors. In all reported cases, the
      diagnosis was only established after resection. Our case presented with recurrent
      pleural effusions mimicking advanced malignancy. Despite careful evaluation and
      biopsies, the diagnosis was only established after resection. We have undertaken
      a literature review of such unusual tumors and emphasize the importance of
      surgical exploration in any patient in whom a tumor lacks histological
      confirmation.

PMID- 10921734
TI  - Thoracoscopic plication of diaphragmatic eventration using endostaplers.
AB  - Unilateral diaphragmatic eventration and paralysis require plication in cases of
      progressive dyspnea on exertion and recurrent respiratory infection. The patient,
      a 40-year-old woman, who had complained of worsening dyspnea on exertion and
      elevation of the left diaphragm on chest radiographs for 4 years, underwent
      plication by thoracoscopy with knifeless endostaplers. Improvements in pulmonary
      functions and dyspnea on exertion have been maintained for 14 months.

PMID- 10921735
TI  - Intrathoracic fibrin sealant application using computed tomography fluoroscopy.
AB  - Persistent intrathoracic airspace and bronchopleural fistula remain a problem
      following lung resection or in patients with severe bullous disease experiencing
      a spontaneous pneumothorax. Although fibrin sealant has been used successfully to
      manage such air-leaks, precise nonoperative intrathoracic application is
      difficult. This report describes a novel technique using computed tomography
      fluoroscopy for catheter-directed FS application through a previously placed
      thoracostomy tube. Continuous computed tomography-fluoroscopy images allowed real
      time catheter manipulation for precise placement of fibrin sealant.

PMID- 10921737
TI  - Pulmonary sequestration with myocardial ischemia caused by vasospasm and steal.
AB  - We describe patient with a rare pulmonary sequestration with myocardial ischemia
      in the left coronary artery caused by vasospastic angina and stealing from
      coronary circulation. The anterior atrial branch from the left circumflex artery
      gave rise to a large and anomalous vessel in the right posterior lung field. Both
      the surgical and medical treatment of this pulmonary sequestration improved the
      control of angina attacks.

PMID- 10921736
TI  - Bronchial stump aspergillosis.
AB  - Two cases of bronchial stump aspergillosis were diagnosed 5 and 6 years after
      pneumonectomy for lung cancer. In each case, the fungal mass was endoscopically
      removed using standard forceps. A recurrence of the fungal mass persisted until
      all visible protruding nylon threads in the airway lumen were destroyed with a
      Nd:YAG laser. Removal of the visible suture is necessary for eliminating the
      infection. No additional local or systemic antifungal therapy is needed.

PMID- 10921738
TI  - Malignant mesothelioma of the pleural space.

PMID- 10921739
TI  - Skeletonization and harvest of the internal thoracic artery with an ultrasonic
      scalpel.
AB  - A new method to skeletonize and harvest the internal thoracic artery using an
      ultrasonic scalpel is presented. The technique is simple, safe, and minimally
      invasive. It is possible to obtain sufficient vessel length for anastomosis to
      most coronary arteries for bypass grafting.

PMID- 10921740
TI  - Reoperative "off-pump" circumflex revascularization via left thoracotomy: how to
      prevent graft kinking.
AB  - Reoperative circumflex revascularization can be performed through a left
      thoracotomy approach, with or without cardiopulmonary bypass. In such cases,
      establishing the appropriate length of coronary grafts connecting the descending
      thoracic aorta to one of the marginal branches of the circumflex coronary artery
      may be problematic. In fact, if these grafts are too long they may kink, whereas
      if left too short they may be injured by respiratory excursions of the left lower
      lobe of the lung. In this report we describe a technique that can prevent these
      potential complications.

PMID- 10921741
TI  - Right axillary cannulation in the left thoracotomy for thoracic aortic aneurysm.
AB  - Perfusion from the femoral artery is commonly used in the open proximal method of
      performing distal aortic arch aneurysm repair or Stanford type B aortic
      dissection repair under circulatory arrest through left thoracotomy. However, it
      is associated with a significant risk of retrograde emboli or malperfusion, and
      with other problems including a restricted time of circulatory arrest to the
      brain and difficulties in de-airing from the arch branches and proximal ascending
      aorta. To overcome these problems, we developed a method of performing right
      axillary perfusion through left thoracotomy.

PMID- 10921742
TI  - Thoracoscopic sympathectomy for hyperhidrosis palmaris: a periareolar approach.
AB  - Severe hyperhidrosis palmaris represents a disabling problem for many patients.
      Thoracoscopic techniques that involve dissection and removal of the upper
      thoracic sympathetic chain are believed to result in the lowest incidence of
      recurrent symptoms. However, aside from an axillary incision, an additional upper
      anterior chest wall approach is usually required. Over the past 2 years, we have
      used a periareolar incision in eight patients to improve postoperative cosmesis
      for this benign condition.

PMID- 10921743
TI  - Thoracoscopic localization of nonpalpable rib tumors for excisional biopsy.
AB  - Nonpalpable tumors of the rib can be difficult to localize accurately at the time
      of excisional biopsy. Furthermore, the ability of current imaging techniques to
      assess pleural or pulmonary involvement is not reliable. An intraoperative
      localization method using single port thoracoscopy is discussed which allows
      optimal placement of a biopsy incision and provides an accurate assessment of any
      tumor invasion into the adjacent pleura or lung.

PMID- 10921744
TI  - Cardiac xenotransplantation: clinical experience and future direction.
AB  - The shortage of human organs has focused research on finding an animal source of
      replacement organs. The immunological barriers to xenotransplantation are now
      more clearly defined, allowing retrospective interpretation of past clinical
      experience in humans. Due to physiological compatibilities as well as ethical and
      infectious considerations, pigs have now emerged as the most likely source of
      future xenografts. The introduction of transgenic pigs expressing human
      complement regulatory proteins and new immunosuppressive regimens have shown
      early promise in the laboratory, although further advancements are needed to
      advance to clinical trials. Additional clarification of infectious risks and
      patient strategies are remaining obstacles to application in the clinical arena.

PMID- 10921745
TI  - Myasthenia gravis: recommendations for clinical research standards. Task Force of
      the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of
      America.

PMID- 10921746
TI  - Heparin coating of bypass systems.

PMID- 10921747
TI  - Mitral valve myxoma concomitant with papillary fibroelastoma.

PMID- 10921748
TI  - Monitoring adequacy of brain oxygenation.

PMID- 10921749
TI  - Lung ischemia during cardiopulmonary bypass.

PMID- 10921750
TI  - Endarterectomy on a beating heart.

PMID- 10921751
TI  - Fatal complication due to a mediastinal tumor.

PMID- 10921752
TI  - Have they really seen the effect of the native coronary blood flow?

PMID- 10921753
TI  - A technical proposal for the complex flail chest.

PMID- 10921754
TI  - Control of airway smooth muscle tone: II-pharmacology of relaxation.

PMID- 10921755
TI  - Asthma on the job: work-related factors in new-onset asthma and in exacerbations
      of pre-existing asthma.
AB  - Occupational asthma (OA) can be defined as variable airways narrowing causally
      related to exposure in the working environment to airborne dusts, gases, vapours
      or fumes. There are many agents in the work-place that can induce asthma or cause
      substantial deterioration in pre-existing asthma. It has been estimated that 5
      15% of adult-onset asthma can be attributed to occupational exposures. Hence
      adult patients, especially those with new-onset asthma, must be investigated with
      regard to occupational risk factors for disease. The prognosis for OA is improved
      if the causal exposure is controlled either by controlling the exposure at the
      workplace or by moving the patient out of the workplace.

PMID- 10921756
TI  - The prevalence of asthma and allergy among university freshmen in Eskisehir,
      Turkey.
AB  - The aim of this study was to determine the current and cumulative prevalence of
      asthma, allergic rhinitis, atopic dermatitis and reactivities to allergen skin
      prick tests (SPT) among university freshmen. The data at the first stage were
      collated through the application of the European Community Respiratory Health
      Survey (-ECRHS-Stage I) questionnaire on 1603 students registering at various
      faculties and vocational colleges of Osmangazi University in Eskisehir, Turkey,
      in the academic year 1997-1998. At the second stage a physical examination as
      well as allergen SPTs were conducted on 151 students. Of the students within the
      study group, six (0.4%) had experienced an asthma attack within the previous 12
      months, 11 (0.7%) had a past of asthma attacks and 123 (8.1%) reported wheezing
      attacks within the previous 12 months. The prevalence of asthma-like symptoms,
      rhinoconjunctivitis and dermatitis were found to be 17.0%, 10.0% and 5.9%
      respectively. Asthma and asthma-like symptoms were found to be significantly more
      prevalent among students who smoked. A positive SPT reaction to more than one
      allergen was found in 14.6% of the students. SPT positivity was 8.3% in
      asymptomatic students, 27.3% in asthmatic students, 14.5% in those with asthma
      like symptoms, 28% in those with non-infectious rhinitis and 7.1% in those with
      dermatitis. In analysis of logistic regression, a history of atopy, as
      ascertained in the questionnaire, was seen to have a significant effect on SPT
      positivity. The rate of self-reported asthma and/or asthma-like symptoms among
      newly enrolled freshmen at the Osmangazi University was found to be lower than in
      other countries. Cigarette smoking was seen to increase such symptoms
      significantly, in comparison to non-smokers.

PMID- 10921757
TI  - A demand valve device decreases exhaust nitric oxide and nitrogen dioxide by
      nitric oxide inhalation with a nasal cannula in the human.
AB  - To improve patients' quality of life and decrease pollution risks to medical
      personnel, we tested the usefulness of a nitric oxide (NO) inhalation system
      consisting of a nasal cannula and a demand valve in an open circuit system. To
      estimate the content of NO entering the lung with the open system, concentrations
      of NO and nitrogen dioxide (NO2) were measured in a mechanical lung model, and
      then nitrocylhaemoglobin (NO-Hb), methaemoglobin (Met-Hb), and nitrite (NO2-) +
      nitrate (NO3-) concentrations in venous blood were measured in eight healthy
      subjects. Exhaust NO and NO2 in the open system were also observed in 14 healthy
      subjects. In the lung model, NO concentration delivered with the open system was
      approximately 1/11 of that in the gas tank. Increases in Met-Hb and NO2- + NO3-
      with the open system showed that the concentration of delivered NO was
      approximately 1/9 of that in the gas tank. The open system reduced exhaust NO to
      1/10 in human subjects. These data suggest that this NO inhalation system
      delivers sufficient NO to spontaneously breathing patients. In addition, these
      findings indicate that there is little environmental toxicity associated with the
      open circuit system.

PMID- 10921758
TI  - Equivalent asthma control after dose reduction with HFA-134a beclomethasone
      solution aerosol. Comparative Inhaled Steroid Investigation Group (CISIG).
AB  - AIM: The replacement of chlorofluorocarbon (CFC) by hydrofluoroalkane has the
      potential to improve airway deposition of BDP. We investigated whether HFA-BDP
      extra-fine solution aerosol 400 microg day(-1) is as effective as CFC-BDP 1000
      micro day(-1) in patients with stable, moderate asthma, having persistent
      bronchial hyperresponsiveness. PATIENTS AND METHODS: One hundred and fifty
      patients with moderate asthma from 20 centres, on inhaled steroids for < or = 3
      months, entered a 4-week run-in period with 1000 microg day(-1) CFC-BDP. Patients
      were then allocated to a 10-week study phase, receiving CFC-BDP 1000 microg day(
      1) or HFA-BDP 400 microg day(-1). Symptom score and PEF were measured daily and
      recorded as biweekly means. Spirometry, PC20FEV1, blood eosinophils and serum ECP
      were determined on days 15, 29, 43 and 71, and compared to the last visit of the
      run-in period. All group members were trained in a quality control centre.
      RESULTS: Treating the population of the HFA-BDP group (n = 72) and the CFC-BDP
      group (n = 78) did not show significant differences in terms of symptoms, lung
      function, airway hyperresponsiveness and serum markers of inflammation at the end
      of the run-in period and the end of the study phase. CONCLUSION: Using HFA
      instead of a CFC metered dose inhaler, containing less than half the daily dose
      of BDP, allows control of symptoms and lung function parameters, without changes
      in bronchial hyperresponsiveness.

PMID- 10921759
TI  - Management of patients with community-acquired pneumonia in a primary care
      hospital: a critical evaluation.
AB  - The aim of the study was to evaluate routine management of patients with
      community-acquired pneumonia (CAP) with regard to severity patterns, diagnostic
      approaches and results, as well as initial empiric antimicrobial treatment and
      its impact on outcome. Two hundred and thirty-two consecutive patients with CAP
      admitted to a primary care hospital were studied prospectively. Patients were
      classified according to Fine's severity score. Severe pneumonia was defined as
      admission at the ICU. Diagnostic approaches and initial antimicrobial treatment
      were judged according to the guidelines of the European Respiratory Society
      (ERS). Fifty-five patients (24%) had mild, 156 (67%) moderate, and 21 (9%) severe
      CAP. At least one microbial examination was performed in 124 patients (54%).
      There was no association between microbial investigation and severity of CAP.
      Inadequate initial antimicrobial treatment was significantly more frequent in
      severe (18/21, 86%), than in mild (5/55, 9%) and moderate CAP (39/156, 25%, P <
      0.0001). Conversely, antimicrobial overtreatment occurred significantly more
      often in mild (30/55, 55%) and moderate (77/156, 49%) than in severe CAP (0/21,
      0%, P < 0.0001). Inadequate initial antimicrobial treatment was more frequent in
      non-responders [18/62 (29%) vs. 31/170, (18%), RR 1.6 95% CI 0.9-2.6, P = 0.07]
      and was associated with a longer duration of hospitalization (17 +/- 11 vs. 14 +/
      8 days, P = 0.03). Mortality was not affected by inadequate initial
      antimicrobial treatment [5/62 (8%) vs. 10/170 (6%), RR 1.4 95% CI 0.5-3.9,
      P=0.55]. Principal conceptual weaknesses which might be subject to intervention
      were (1) the hospitalization of patients with mild pneumonia at low risk of
      mortality; (2) the lack of association between microbial investigation and
      severity of CAP; (3) antimicrobial overtreatment of patients with non-severe CAP;
      and (4) inadequate antimicrobial treatment with increased number of primary
      treatment failures and duration of hospitalization.

PMID- 10921760
TI  - Human neutrophil lipocalin (HNL) and myeloperoxidase (MPO). Studies of lung
      lavage fluid and lung tissue.
AB  - Myeloperoxidase (MPO) and human neutrophil lipocalin (HNL) are proteins which are
      stored in neutrophil granulocytes, in the primary and secondary granules,
      respectively. These granules or their contents of MPO and HNL are secreted upon
      activation of the cells, and measurement of these soluble markers in biological
      fluids, such as bronchoalveolar lavage (BAL), has been proposed to mirror the
      degree of neutrophil activity in the tissue. We conducted a BAL study in 10
      healthy volunteers, with the aim to evaluate the intra-individual variability of
      the concentration of HNL and MPO recovered in sequential aspirations, during a
      time period when the concentrations of HNL and MPO in BAL fluids were considered
      to have equilibrated with those in the underlying tissues. The concentrations of
      HNL were less variable than those of MPO (coefficients of variability 0.33 +/-
      0.07 vs. 0.92 +/- 0.28; P = 0.01), suggesting HNL to be a more useful marker of
      neutrophil activity within the airspace. The specificity of HNL as a selective
      index of neutrophil cells was confirmed by means of immunohistochemical staining
      of uninvolved lung tissue specimens obtained from patients referred to
      pulmonectomy due to carcinoma. While HNL was located only to intracellular spaces
      of neutrophils, MPO was in addition located to other cells as well. We speculate
      that the dynamic changes of pressure across the membranes and flow of solutes
      during a lavage process might mobilize particulate matter and adherent cells,
      some of which may be loaded with MPO, and that this may introduce larger
      variability in the recovery of MPO than of HNL. We conclude that using HNL as a
      soluble indicator of neutrophil presence is more feasible than using MPO.

PMID- 10921761
TI  - The accuracy of subjective sleep time in sleep apnoea recordings.
AB  - Total sleep time is important in investigations of obstructive sleep apnoea,
      since the diagnosis is usually based on the average number of apnoeas per hour of
      sleep. Sleep estimates instead of exact EEG-recorded total sleep time is often
      used in the clinical setting. However, an overestimated sleep time would
      underestimate the degree of the disease and vice versa. The purpose of this study
      was to investigate the accuracy of subjective sleep time and time-in-bed as sleep
      estimates. One hundred patients undergoing diagnostic polysomnography for
      suspected obstructive sleep apnoea were asked to estimate their sleep time in a
      questionnaire. Seventy-five patients were diagnosed as suffering from obstructive
      sleep apnoea syndrome. The mean difference between self-scored and EEG-recorded
      total sleep time was 4 +/- 74 min. However, 30% scored with a difference greater
      than 1 h. The intra-class correlation coefficient was fair (0.58, CI: 0.43-0.70).
      Fifty-three patients overestimated their sleep time and 47 patients
      underestimated it. All but four patients underestimated their number of
      awakenings (P<0.001). The mean difference between time-in-bed and EEG-recorded
      total sleep time was 110 +/- 63 min. This difference was significantly larger
      than the difference between subjective sleep time and EEG-recorded total sleep
      time (P<0.001). The intra-class correlation coefficient was poor (0.38, CI: 0.20
      0.54). Mean AHI was 27 +/- 27 using subjective sleep time and did not change
      significantly compared with the mean AHI of 25 +/- 21 based on EEG-recorded total
      sleep time. Mean AHI decreased significantly to 20 +/- 17 (P<0.001) when time-in
      bed was used. In conclusion, 'time-in-bed' time is a poor predictor of total
      sleep time and should not be used when calculating the apnoea-hypopnoea index.
      Subjective sleep time is better as an approximation, but the individual
      differences are large.

PMID- 10921762
TI  - Equivalent therapeutic ratio of salbutamol given by Turbuhaler and Diskus.
AB  - Some inhalers have been claimed to give better deposition, resulting in higher
      efficacy. In a previous study we did not find any evidence of different potency
      of salbutamol given either via pMDI or Turbuhaler. The aim of the present study
      was to compare the efficacy and safety of salbutamol given via Diskus or
      Turbuhaler. Twenty-five asthmatics with step-wise reversible airflow obstruction
      (total reversibility of at least 15%) were included in a randomized, double
      dummy, placebo-controlled cross-over study. On each study day, the patients were
      given placebo repeatedly, or cumulative doses of 200, 400, 800, 1600 and 3200
      microg salbutamol given via either device (double-blind, placebo-controlled).
      Salbutamol caused a dose-related increase in FEV1 when given by Diskus or
      Turbuhaler. The improvement in FEV1 was similar regardless of whether salbutamol
      was given via Diskus or Turbuhaler, at equivalent microgram doses. After a total
      cumulative dose of 3200 microg, mean FEV1 for Diskus was 2.46 l (change from
      baseline of 20.5%), for Turbuhaler 2.50 l (change from baseline 24.6%) and for
      placebo 2.11 l (3% change from baseline). After correcting for different baseline
      differences, the percentage difference between Diskus and Turbuhaler was -1.8% (P
      = 0.2). Systemic effects (potassium and heart rate) did not differ between Diskus
      or Turbuhaler. We conclude that the efficacy of salbutamol given at equivalent
      microgram doses, as well as side-effects, are comparable when the drug is given
      via Diskus or Turbuhaler. The present data shows that salbutamol given by these
      devices have similar therapeutic ratios.

PMID- 10921763
TI  - Prescribing patterns for asthma by general practitioners in six European
      countries.
AB  - To assess the level of concordance with international consensus on asthma
      management, we compared primary care prescribing patterns for asthma in different
      European countries. A prospective study of prescription items with an associated
      diagnostic label of asthma in patient consultations with a total of 235 general
      practitioners (GPs) from Belgium, England, Ireland, Italy, Northern Ireland,
      Portugal, Scotland and Spain was performed. A total of 101,544 consecutive
      consultations were recorded in autumns 1994 and 1995 of which 3595 (3.5%) were
      for patients with asthma and 3243 (3.2%) were for patients receiving a
      prescription for asthma. Overall, asthma consultations varied from 1.8% in Italy
      to 5.8% in Ireland (mean 3.4%, SD 1.6). Prescribed inhaled medications for
      children varied from 72% of the total asthma prescriptions in Ireland and
      Portugal to 82% in Northern Ireland (mean 79%, SD 8.1) and for adults 55% in
      Italy to 85% in Spain (mean 70%, SD 10). Inhaled corticosteroid usage for adults
      varied from 14% in Italy to 31% in Northern Ireland (mean 24%, SD 6.4). For
      children, beta2-agonist use varied from 24% in Italy to 67% in Spain (mean 45%,
      SD 13). Despite publication of international guidelines for the management of
      asthma, inter-country prescribing practices vary considerably and could be
      improved. The frequency of use of asthma as a diagnostic label also varies
      markedly.

PMID- 10921764
TI  - Evidence of oxidative stress in asthma and COPD: potential inhibitory effect of
      theophylline.
AB  - To evaluate the potential inhibitory effect of theophylline on the pulmonary
      oxidative stress in asthma and chronic obstructive pulmonary disease (COPD), we
      concomitantly measured the blood levels of theophylline, a non-selective
      phosphodiesterase (PDE) inhibitor and lipid peroxides as an index of oxidative
      stress. The plasma levels of lipid peroxides were significantly elevated in
      patients with asthma (3.48 +/- 0.11 nmol ml(-1); mean +/- SEM; n=21, P<0.01), non
      or ex-smoking patients with COPD (3.55 +/- 0.11 nmol ml(-1); n = 20, P<0.01),
      and current-smoking patients with COPD (3.53 +/- 0.15 nmol ml(-1); n = 15,
      P<0.01), respectively, as compared to those of non-smoking controls (3.02 +/-
      0.08 nmol ml(-1); n = 19). There was a significant negative correlation between
      the plasma level of lipid peroxides and the forced expiratory volume in 1 sec
      (FEV1)% of forced vital capacity in these subjects (r = -0.304; n = 75, P <
      0.01). In asthmatics, there was a significant negative correlation between the
      plasma level of lipid peroxides and the serum level of theophylline (r = -0.495;
      n = 18, P<0.05). These results suggest that there may be increased oxidative
      stress in patients with asthma and COPD, and indicate that oxidative stress could
      possibly attribute to the pathophysiology of asthma and COPD in leading to
      airflow obstruction and that theophylline could potentially inhibit oxidative
      stress in the process of bronchopulmonary inflammation in asthmatics.

PMID- 10921765
TI  - Development and validation of a standardized measure of activity of daily living
      in patients with severe COPD: the London Chest Activity of Daily Living scale
      (LCADL).
AB  - Activities of daily living (ADL) may be severely restricted in patients with COPD
      and assessment requires evaluation of the impact of disability and handicap on
      daily life. This study is concerned with the development and validation of a
      standardized 15-item questionnaire to assess routine ADL. Sixty (33 male, 27
      female) patients with severe COPD, mean (SD) FEV1 0.91 (0.43) l, median (range)
      age 70 (50-82) years, completed a 59-item ADL list previously generated by open
      ended interview and by literature review. Patients also performed the Shuttle
      Walk Test (SWT), and completed the St George's Respiratory Questionnaire (SGRQ),
      the Nottingham Extended Activity of Daily Living Questionnaire (EADL) and the
      Hospital Anxiety and Depression score (HAD). Criteria for item reduction in the
      development of The London Chest ADL scale (LCADL) consisted of removal of items
      where the majority of respondents showed no limitation in the activity (n = 19),
      where there was no association with perception of global health (n = 9), where an
      association with age or gender was detected (n = 4), or where items showed poor
      reliability on test re-test (n = 9). Fifteen items were identified as core
      activities of daily living. The LCADL was then compared with other measures of
      health status in these patients. There were good correlations with the SGRQ
      activity and impact components (p=0.70; P<0.0001) and (p=0.58; P<0.0001),
      respectively, and EADL (p=0.45; P<0.001), and a moderate correlation with HAD
      anxiety (p=0.28; P<0.03). There was a significant relationship between the SWT
      and LCADL (p=0.58; P<0.0001), suggesting a relationship between impaired exercise
      performance and lower ADL scores. There was evidence of high internal consistency
      of the questionnaire with Chronbach's alpha of 0.98. These findings suggest that
      the LCADL scale is a valid tool for the assessment of ADL in patients with severe
      COPD.

PMID- 10921766
TI  - Patient-assessed measures of health outcome in asthma: a comparison of four
      approaches.
AB  - The study compares the psychometric properties of four different approaches to
      patient-assessed health outcomes in asthma, including the Asthma Quality of Life
      Questionnaire (AQLQ), Newcastle Asthma Symptoms Questionnaire (NASQ), SF-12 and
      EuroQol. The instruments were administered by means of a self-completed postal
      questionnaire to 394 patients recruited from general practices in the North East
      of England. Patients completed a follow-up questionnaire at 6 months. The levels
      of missing data were assessed and instrument scores compared using correlational
      analysis. Scores were related to self-reports of smoking behaviour, socioeconomic
      status and health transition. Responsiveness was assessed using standardized
      response means. Two hundred and thirty-five patients took part in the study
      giving a response rate of 59.6%. There was a relatively large amount of missing
      data for the individualized section of the AQLQ. Correlational analysis provided
      evidence of convergent validity between the specific instruments; the largest
      correlation was found between NASQ scores and the asthma symptoms scale of the
      AQLQ (r = 0.84). The NASQ was found to be the most powerful at discriminating
      between smokers and non-smokers. All four instruments were linearly related to
      self-reported asthma transition (P<0.05); the specific instruments having the
      strongest association. The specific instruments showed good levels of
      responsiveness with the NASQ producing a large SRM of 0.82. SRMs for the AQLQ
      were of a moderate to large size (0.32-0.77) and the SRMs for the SF-12 and
      EuroQol were of a small size. The two specific instruments are capable of greater
      levels of discrimination between groups of patients and are more responsive to
      changes in health than the generic SF-12 and EuroQol. The greater responsiveness
      of the NASQ is probably due to its focus being restricted to symptoms of asthma
      compared to the broader focus of the AQLQ domains. The NASQ has a strong
      relationship with the AQLQ and is a more practical instrument that is more
      acceptable to patients. However, the AQLQ does measure broader patient concerns.
      The SF-12 and EuroQol have greater potential to capture side-effects and have
      wider scope for application in economic evaluation.

PMID- 10921767
TI  - Oxis (formoterol given by Turbuhaler) showed as rapid an onset of action as
      salbutamol given by a pMDI.
AB  - Thirty-six adult patients (16 women) with mild to moderate asthma with a mean
      baseline forced expiratory volume in 1 sec (FEV1) of 73.8% (46-106%) of predicted
      normal value and mean reversibility of 24.2% (14.6-47.1%) were included in this
      double-blind, double-dummy, randomized, placebo-controlled and cross-over study.
      The patients inhaled single doses 4.5 or 9 microg of formoterol (Oxis) via
      Turbuhaler salbutamol (Ventolin) 100 or 200 microg from a pressurized metered
      dose inhaler (pMDI) or placebo at five randomized visits. Efficacy was measured
      by FEV1 pre-dose and then 1, 3, 5, 7, 10, 15, 20, 25 and 30 min after inhalation
      of the study drug. The primary variable of efficacy was the FEV1-value 3 min
      after dose intake. No statistically significant differences were found between
      active treatments. All active treatments gave a higher bronchodilating effect at
      3 min than placebo: 10.0, 11.4% for salbutamol 100 and 200 microg and 11.7, 11.8%
      for formoterol 4.5 and 9 microg (P<0.001 in all cases). There was a correlation
      between the measured response at 3 min and the subjective experience of the
      patients. The relative difference vs. placebo remained throughout the study
      period for all active treatments except for low dose salbutamol. All treatments
      were well tolerated. In conclusion, formoterol Turbuhaler has as rapid an onset
      of action as salbutamol pMDI when given at recommended doses.

PMID- 10921769
TI  - Factor Xa: simulation studies with an eye to inhibitor design.
AB  - Factor Xa is a serine protease which activates thrombin and plays a key
      regulatory role in the blood-coagulation cascade. Factor Xa is at the crossroads
      of the extrinsic and intrinsic pathways of coagulation and, hence, has become an
      important target for the design of anti-thrombotics (inhibitors). It is not known
      to be involved in other processes than hemostasis and its binding site is
      different to that of other serine proteases, thus facilitating selective
      inhibition. The design of high-affinity selective inhibitors of factor Xa
      requires knowledge of the structural and dynamical characteristics of its active
      site. The three-dimensional structure of factor Xa was resolved by X-ray
      crystallography and refined at 2.2 A resolution by Padmanabhan and collaborators.
      In this article we present results from molecular dynamics simulations of the
      catalytic domain of factor Xa in aqueous solution. The simulations were performed
      to characterise the mobility and flexibility of the residues delimiting the
      unoccupied binding site of the enzyme, and to determine hydrogen bonding
      propensities (with protein and with solvent atoms) of those residues in the
      active site that could interact with a substrate or a potential inhibitor. The
      simulation data is aimed at facilitating the design of high-affinity selective
      inhibitors of factor Xa.

PMID- 10921770
TI  - Computer-aided design and activity prediction of leucine aminopeptidase
      inhibitors.
AB  - The Ligand Design (LUDI) approach has been used in order to design leucine
      aminopeptidase inhibitors, predict their activity and analyze their interactions
      with the enzyme. The investigation was based on the crystal structure of bovine
      lens leucine aminopeptidase (LAP) complexed with its inhibitor--the phosphonic
      acid analogue of leucine (LeuP). More than 50 potential leucine aminopeptidase
      inhibitors have been obtained, including the most potent aminophosphonic LAP
      inhibitors with experimentally known activity, which have been the subject of
      more detailed studies. A reasonable agreement between theoretical and
      experimental activities has been obtained for most of the studied inhibitors. Our
      results confirm that LUDI is a powerful tool for the design of enzyme inhibitors
      as well as in the prediction of their activity. In addition, for inhibitor-active
      site interactions dominated by the electrostatic effects it is possible to
      improve binding energy estimates by using a more accurate description of
      inhibitor charge distribution.

PMID- 10921768
TI  - Montelukast or salmeterol combined with an inhaled steroid in adult asthma:
      design and rationale of a randomized, double-blind comparative study (the IMPACT
      Investigation of Montelukast as a Partner Agent for Complementary Therapy-trial).
AB  - Asthma patients who continue to experience symptoms despite taking regular
      inhaled corticosteroids represent a management challenge. Leukotrienes play a key
      role in asthma pathophysiology, and since pro-inflammatory leukotrienes are
      poorly suppressed by corticosteroids it seems rational to add a leukotriene
      receptor antagonist (LTRA) when a low to moderate dose of inhaled corticosteroids
      does not provide sufficient disease control. Long acting beta2-agonist (LABA)
      treatment represents an alternative to LTRAs and both treatment modalities have
      been shown to provide additional disease control when added to corticosteroid
      treatment. To compare the relative clinical benefits of adding either a LTRA or a
      LABA to asthma patients inadequately controlled by inhaled corticosteroids, a
      randomized, double-blind, multi-centre, 48-week study will be initiated at
      approximately 120 centres throughout Europe, Latin America, Middle East, Africa
      and the Asia-Pacific region in early 2000. The study will compare the oral LTRA
      montelukast with the inhaled LABA salmeterol, each administered on a background
      of inhaled fluticasone, on asthma attacks, quality of life, lung function,
      eosinophil levels, healthcare utilization, and safety, in approximately 1200
      adult asthmatic patients. The requirements for study enrollment include a history
      of asthma, FEV1 or PEFR values between 50% and 90% of the predicted value
      together with > or = 12% improvement in FEV1 after beta-agonist administration, a
      minimum pre-determined level of asthma symptoms and daily beta-agonist
      medication. The study will include a 4-week run-in period, during which patients
      previously taking inhaled corticosteroids are switched to open-label fluticasone
      (200 microg daily), followed by a 48-week double-blind, treatment period in which
      patients continuing to experience abnormal pulmonary function and daytime
      symptoms are randomized to receive montelukast (10 mg once daily) and salmeterol
      placebo, or inhaled salmeterol (100 microg daily) and montelukast placebo. All
      patients will continue with inhaled fluticasone (200 microg daily). During the
      study, asthma attacks, overnight asthma symptoms, and morning peak expiratory
      flow rate will be assessed using patient diary cards; quality of life will also
      be assessed using an asthma-specific quality-of life questionnaire. The results
      of this study are expected to provide physicians with important clinical evidence
      to help them make a rational and logical treatment choice for asthmatic patients
      experiencing breakthrough symptoms on inhaled corticosteroids.

PMID- 10921771
TI  - Refinement of Catalyst hypotheses using simplex optimisation.
AB  - The program HypoOpt in combination with the MSI program citest has been used to
      optimise and expand 3D QSAR Catalyst hypotheses using simplex optimisation
      coupled with cross-validation. Three data sets related to angiotensin converting
      enzyme inhibition, squalene epoxidase inhibition and HIV protease inhibition were
      used to investigate the outcome of hypothesis optimisation. Simplex optimisation
      using leave-one-out cross-validation during the hypothesis refinement resulted in
      improved models with respect to predictivity of an external test set.
      Furthermore, the utilisation of the geometry of the active site for the HIV
      protease inhibitors, represented by Catalyst 'excluded volume' features, resulted
      in an optimised hypothesis with improved predictivity compared with the
      corresponding hypothesis derived without receptor information.

PMID- 10921772
TI  - Receptor-based 3D QSAR analysis of estrogen receptor ligands--merging the
      accuracy of receptor-based alignments with the computational efficiency of ligand
      based methods.
AB  - One of the major challenges in computational approaches to drug design is the
      accurate prediction of binding affinity of biomolecules. In the present study
      several prediction methods for a published set of estrogen receptor ligands are
      investigated and compared. The binding modes of 30 ligands were determined using
      the docking program AutoDock and were compared with available X-ray structures of
      estrogen receptor-ligand complexes. On the basis of the docking results an
      interaction energy-based model, which uses the information of the whole ligand
      receptor complex, was generated. Several parameters were modified in order to
      analyze their influence onto the correlation between binding affinities and
      calculated ligand-receptor interaction energies. The highest correlation
      coefficient (r2 = 0.617, q2Loo = 0.570) was obtained considering protein
      flexibility during the interaction energy evaluation. The second prediction
      method uses a combination of receptor-based and 3D quantitative structure
      activity relationships (3D QSAR) methods. The ligand alignment obtained from the
      docking simulations was taken as basis for a comparative field analysis applying
      the GRID/GOLPE program. Using the interaction field derived with a water probe
      and applying the smart region definition (SRD) variable selection, a significant
      and robust model was obtained (r2 = 0.991, q2LOO = 0.921). The predictive ability
      of the established model was further evaluated by using a test set of six
      additional compounds. The comparison with the generated interaction energy-based
      model and with a traditional CoMFA model obtained using a ligand-based alignment
      (r2 = 0.951, q2L00 = 0.796) indicates that the combination of receptor-based and
      3D QSAR methods is able to improve the quality of the underlying model.

PMID- 10921773
TI  - A novel method of aligning molecules by local surface shape similarity.
AB  - A novel shape-based method has been developed for overlaying a series of molecule
      surfaces into a common reference frame. The surfaces are represented by a set of
      circular patches of approximately constant curvature. Two molecules are overlaid
      using a clique-detection algorithm to find a set of patches in the two surfaces
      that correspond, and overlaying the molecules so that the similar patches on the
      two surfaces are coincident. The method is thus able to detect areas of local,
      rather than global, similarity. A consensus overlay for a group of molecules is
      performed by examining the scores of all pairwise overlays and performing a set
      of overlays with the highest scores. The utility of the method has been examined
      by comparing the overlaid and experimental configurations of 4 sets of molecules
      for which there are X-ray crystal structures of the molecules bound to a protein
      active site. Results for the overlays are generally encouraging. Of particular
      note is the correct prediction of the 'reverse orientation' for ligands binding
      to human rhinovirus coat protein HRV14.

PMID- 10921775
TI  - A new method for the simultaneous measurement of magnitude and sign of 1DCH and
      1DHH dipolar couplings in methylene groups.
AB  - Heteronuclear dipolar couplings of the protein backbone have proven to have a big
      impact on the accuracy of protein NMR structures. H,H dipolar couplings might
      have the same impact on side chains. Here we present a method that combines both
      heteronuclear and homonuclear dipolar couplings to investigate the local
      conformation of methylene groups. A new pulse sequence (SPITZE-HSQC) is
      presented, that allows to measure the two C,H and the H,H dipolar couplings at
      the same time, using spin state selective transfers. The new method has been
      applied to the methylene groups of glycines in the protein ubiquitin. The C,H and
      the H,H dipolar couplings might have a key role in fast stereospecific assignment
      of protons in CH2 groups.

PMID- 10921774
TI  - Identification of ligands for RNA targets via structure-based virtual screening:
      HIV-1 TAR.
AB  - Binding of the Tat protein to TAR RNA is necessary for viral replication of HIV
      1. We screened the Available Chemicals Directory (ACD) to identify ligands to
      bind to a TAR RNA structure using a four-step docking procedure: rigid docking
      first, followed by three steps of flexible docking using a pseudobrownian Monte
      Carlo minimization in torsion angle space with progressively more detailed
      conformational sampling on a progressively smaller list of top-ranking compounds.
      To validate the procedure, we successfully docked ligands for five RNA complexes
      of known structure. For ranking ligands according to binding avidity, an
      empirical binding free energy function was developed which accounts, in
      particular, for solvation, isomerization free energy, and changes in
      conformational entropy. System-specific parameters for the function were derived
      on a training set of RNA/ligand complexes with known structure and affinity. To
      validate the free energy function, we screened the entire ACD for ligands for an
      RNA aptamer which binds L-arginine tightly. The native ligand ranked 17 out of
      ca. 153,000 compounds screened, i.e., the procedure is able to filter out >99.98%
      of the database and still retain the native ligand. Screening of the ACD for TAR
      ligands yielded a high rank for all known TAR ligands contained in the ACD and
      suggested several other potential TAR ligands. Eight of the highest ranking
      compounds not previously known to be ligands were assayed for inhibition of the
      Tat-TAR interaction, and two exhibited a CD50 of ca. 1 microM.

PMID- 10921776
TI  - Three-dimensional structure determination of a uniformly labeled molecule by
      frequency-selective dipolar recoupling under magic-angle spinning.
AB  - The complete three-dimensional (3D) structure of a glycylisoleucine (Gly-Ile)
      molecule was determined by individually measuring six dihedral angles with a
      frequency-selective homonuclear dipolar recoupling method, R2TR (rotational
      resonance in the tilted rotating frame), using a powder sample of diluted
      uniformly 13C,15N-labeled Gly-Ile. Each dihedral angle was obtained by recoupling
      a dipolar interaction between three or four bonds distant spins concerned or
      observing a dipolar correlation 2D powder pattern. The 3D structure of a Gly-Ile
      molecule was also determined by X-ray crystallography, and a good agreement with
      the NMR result was obtained. The results demonstrate that the R2TR method in a
      uniformly labeled powder sample can provide the 3D structure without the need to
      prepare a lot of selectively labeled samples.

PMID- 10921777
TI  - A tracked approach for automated NMR assignments in proteins (TATAPRO).
AB  - A novel automated approach for the sequence specific NMR assignments of 1HN,
      13Calpha, 13Cbeta, 13C'/1Halpha and 15N spins in proteins, using triple resonance
      experimental data, is presented. The algorithm, TATAPRO (Tracked AuTomated
      Assignments in Proteins) utilizes the protein primary sequence and peak lists
      from a set of triple resonance spectra which correlate 1HN and 15N chemical
      shifts with those of 13Calpha, 13Cbeta and 13C'/1Halpha. The information derived
      from such correlations is used to create a 'master-_list' consisting of all
      possible sets of 1HN(i), 15N(i)13Calpha(i),13Cbeta(i) 13C'beta(i)/1Halpha(i),
      13Calpha(i-1), 13Cbeta(i-1) and 13C'(i-1)/1Halpha(i-1) chemical shifts. On the
      basis of an extensive statistical analysis of 13Calpha and 13Cbeta chemical shift
      data of proteins derived from the BioMagResBank (BMRB), it is shown that the 20
      amino acid residues can be grouped into eight distinct categories, each of which
      is assigned a unique two-digit code. Such a code is used to tag individual sets
      of chemical shifts in the master_list and also to translate the protein primary
      sequence into an array called pps_array. The program then uses the master_list to
      search for neighbouring partners of a given amino acid residue along the
      polypeptide chain and sequentially assigns a maximum possible stretch of residues
      on either side. While doing so. each assigned residue is tracked in an array
      called assig_array, with the two-digit code assigned earlier. The assig_array is
      then mapped onto the pps_array for sequence specific resonance assignment. The
      program has been tested using experimental data on a calcium binding protein from
      Entamoeba histolytica (Eh-CaBP, 15 kDa) having substantial internal sequence
      homology and using published data on four other proteins in the molecular weight
      range of 18-42 kDa. In all the cases, nearly complete sequence specific resonance
      assignments (> 95%) are obtained. Furthermore, the reliability of the program has
      been tested by deleting sets of chemical shifts randomly from the master_list
      created for the test proteins.

PMID- 10921778
TI  - RFAC, a program for automated NMR R-factor estimation.
AB  - A computer program (RFAC) has been developed, which allows the automated
      estimation of residual indices (R-factors) for protein NMR structures and gives a
      reliable measure for the quality of the structures. The R-factor calculation is
      based on the comparison of experimental and simulated 1H NOESY NMR spectra. The
      approach comprises an automatic peak picking and a Bayesian analysis of the data,
      followed by an automated structure based assignment of the NOESY spectra and the
      calculation of the R-factor. The major difference to previously published R
      factor definitions is that we take the non-assigned experimental peaks into
      account as well. The number and the intensities of the non-assigned signals are
      an important measure for the quality of an NMR structure. It turns out that for
      different problems optimally adapted R-factors should be used which are defined
      in the paper. The program allows to compute a global R-factor, different R
      factors for the intra residual NOEs, the inter residual NOEs, sequential NOEs,
      medium range NOEs and long range NOEs. Furthermore, R-factors can be calculated
      for various user defined parts of the molecule or it is possible to obtain a
      residue-by-residue R-factor. Another possibility is to sort the R-factors
      according to their corresponding distances. The summary of all these different R
      factors should allow the user to judge the structure in detail. The new program
      has been successfully tested on two medium sized proteins, the cold shock protein
      (TmCsp) from Termotoga maritima and the histidine containing protein (HPr) from
      Staphylococcus carnosus. A comparison with a previously published R-factor
      definition shows that our approach is more sensitive to errors in the calculated
      structure.

PMID- 10921780
TI  - The use of chemical shift temperature gradients to establish the paramagnetic
      susceptibility tensor orientation: implication for structure
      determination/refinement in paramagnetic metalloproteins.
AB  - The use of dipolar shifts as important constraints in refining molecular
      structure of paramagnetic metalloproteins by solution NMR is now well
      established. A crucial initial step in this procedure is the determination of the
      orientation. of the anisotropic paramagnetic susceptibility tensor in the
      molecular frame which is generated interactively with the structure refinement.
      The use of dipolar shifts as constraints demands knowledge of the diamagnetic
      shift. which, however, is very often not directly and easily accessible. We
      demonstrate that temperature gradients of dipolar shifts can serve as alternative
      constraints for determining the orientation of the magnetic axes, thereby
      eliminating the need to estimate the diamagnetic shifts. This approach is tested
      on low-spin, ferric sperm whale cyanometmyoglobin by determining the orientation,
      anisotropies and anisotropy temperature gradients by the alternate routes of
      using dipolar shifts and dipolar shift gradients as constraints. The alternate
      routes ultimately lead to very similar orientation of the magnetic axes, magnetic
      anisotropies and magnetic anisotropy temperature gradients which, by inference,
      would lead to an equally valid description of the molecular structure. It is
      expected that the use of the dipolar shift temperature gradients, rather than the
      dipolar shifts directly, as constraints will provide an accurate shortcut in a
      solution structure determination of a paramagnetic metalloprotein.

PMID- 10921781
TI  - Sequence-specific 1H, 13C, and 15N assignments of the MAR-binding domain of
      chicken MeCP2/ARBP.

PMID- 10921779
TI  - Interactions of a didomain fragment of the Drosophila sex-lethal protein with
      single-stranded uridine-rich oligoribonucleotides derived from the transformer
      and Sex-lethal messenger RNA precursors: NMR with residue-selective [5-2H]uridine
      substitutions.
AB  - Proteins that contain two or more copies of the RNA-binding domain
      [ribonucleoprotein (RNP) domain or RNA recognition motif (RRM)] are considered to
      be involved in the recognition of single-stranded RNA, but the mechanisms of this
      recognition are poorly understood at the molecular level. For an NMR analysis of
      a single-stranded RNA complexed with a multi-RBD protein, residue-selective
      stable-isotope labeling techniques are necessary, rather than common assignment
      methods based on the secondary structure of RNA. In the present study, we
      analyzed the interaction of a Drosophila Sex-lethal (Sx1) protein fragment,
      consisting of two RBDs (RBD1-RBD2), with two distinct target RNAs derived from
      the tra and Sxl mRNA precursors with guanosine and adenosine, respectively, in a
      position near the 5'-terminus of a uridine stretch. First, we prepared a [5
      2H]uridine phosphoramidite, and synthesized a series of 2H-labeled RNAs, in which
      all of the uridine residues except one were replaced by [5-2H]uridine in the
      target sequence, GU8C. By observing the H5-H6 TOCSY cross peaks of the series of
      2H-labeled RNAs complexed with the Sx1 RBDI-RBD2, all of the base H5-H6 proton
      resonances of the target RNA were unambiguously assigned. Then, the H5-H6 cross
      peaks of other target RNAs, GU2GU8, AU8, and UAU8, were assigned by comparison
      with those of GU8C. We found that the uridine residue prior to the G or A residue
      is essential for proper interaction with the protein, and that the interaction is
      tighter for A than for G. Moreover, the H1' resonance assignments were achieved
      from the H5-H6 assignments. The results revealed that all of the protein-bound
      nucleotide residues, except for only two, are in the unusual C2'-endo ribose
      conformation in the complex.

PMID- 10921782
TI  - Sequence-specific resonance assignments of Q83, a lipocalin highly expressed in v
      myc-transformed avian fibroblasts.

PMID- 10921783
TI  - 1H, 15N and 13C resonance assignments for the C-terminal protein interaction
      region of the 32 kDa subunit of human replication protein A.

PMID- 10921784
TI  - 1H, 13C and 15N resonance assignments of the DNA binding domain of the human
      forkhead transcription factor AFX.

PMID- 10921785
TI  - Assignment of 1H, 13C and 15N resonances of FKBP. from Methanococcus
      thermolithotrophicus.

PMID- 10921786
TI  - Analysis of the pattern of initiation of sustained ventricular arrhythmias in
      patients with implantable defibrillators.
AB  - INTRODUCTION: The purpose of this study was to analyze the pattern of initiation
      of sustained ventricular arrhythmias in patients with varying types of underlying
      structural heart disease. METHODS AND RESULTS: The study group consisted of 90
      patients with an implantable cardioverter defibrillator. Cardiovascular diagnoses
      included coronary artery disease in 64 patients (71%). The patients were divided
      into four groups based on the type and severity of structural heart disease. Two
      hundred sixty episodes of sustained ventricular arrhythmias were analyzed. The
      mean coupling interval of the initiating beat of all ventricular arrhythmias was
      523 +/- 171 msec. The coupling interval of the initiating beat was longer in
      patients with impaired ventricular function, particularly those with nonischemic
      dilated cardiomyopathy. The prematurity index was similar regardless of the type
      of underlying structural heart disease. However, the prematurity index was
      shorter in patients with polymorphic ventricular tachycardia (VT) compared to
      those with monomorphic VT. A pause was observed more commonly before the onset of
      polymorphic VT/ventricular fibrillation than sustained monomorphic VT. Two
      hundred twenty-two (85%) of the arrhythmia episodes were initiated by a late
      coupled premature beat, 33 (13%) were initiated by an early-coupled premature
      beat, and 5 episodes (2%) were initiated with a short-long-short sequence. The
      pattern of initiation of the ventricular arrhythmias was similar in all patient
      groups and for both monomorphic and polymorphic tachycardias. CONCLUSION: These
      findings demonstrate that sustained ventricular arrhythmias typically are
      initiated by late-coupled ventricular premature depolarizations, regardless of
      the type or severity of underlying structural heart disease or resultant
      arrhythmia.

PMID- 10921787
TI  - Initiation of spontaneous ventricular tachycardia: from spark to fire.

PMID- 10921788
TI  - Unusual features of intermediate septal bypass tracts.
AB  - INTRODUCTION: Intermediate septal (IS) AV bypass tracts, located along the
      tricuspid annulus between the His bundle and coronary sinus os, lie in close
      proximity to the AV node. Surgical or catheter ablation of IS bypass tracts
      incurs increased risk for development of complete heart block. We report
      additional unusual features of some IS bypass tracts that distinguish them from
      typical bypass tracts in other anatomic regions. METHODS AND RESULTS: We analyzed
      a consecutive series of 150 patients with a history of Wolff-Parkinson-White
      syndrome and supraventricular tachycardia who underwent ablation of bypass
      tracts. We studied the incidence and characteristics of AV conduction of IS
      bypass tracts compared with bypass tracts in other locations. Of the 150 patients
      in the study, 21 had an IS bypass tract (all had anterograde AV conduction). Ten
      (48%) of these 21 IS bypass tracts demonstrated anterograde decremental
      properties with atrial pacing versus 3 (2%) of 129 non-IS bypass tracts (P <
      0.001). During ablation, a change in delta wave morphology before total loss of
      conduction in the IS bypass tract also occurred in 3 (14%) of 21 IS bypass tracts
      versus 0 of 129 non-IS bypass tracts (P = 0.0004). During ablation, a change in P
      wave to delta wave interval occurred in 4 (19%) of 21 IS bypass tracts versus 0
      of 129 non-IS bypass tracts (P < 0.0001). One IS patient exhibited retrograde
      Wenckebach block in the bypass tract, and two IS patients showed loss of
      retrograde bypass tract conduction after ablation attempts that first changed the
      delta wave morphology. No non-IS patient had these features (P < 0.0001 for each
      comparison). CONCLUSION: Some IS bypass tracts have unusual properties that
      distinguish them from bypass tracts in other locations, perhaps due to the
      presence of multiple ventricular insertions of the bypass tract. It is possible
      that some cases represent true "nodoventricular" pathways.

PMID- 10921789
TI  - Effect of chronic amiodarone therapy on defibrillation energy requirements in
      humans.
AB  - INTRODUCTION: The effect of oral amiodarone therapy on defibrillation energy
      requirements in patients with an implantable defibrillator has not been
      established. METHODS AND RESULTS: Twenty-one consecutive patients with
      implantable biphasic waveform defibrillators underwent a step-down determination
      of the defibrillation energy requirement 211 +/- 12 days before and 73 +/- 22
      days after initiation of amiodarone therapy (mean total dose 26.7 +/- 11.1 g).
      Serum amiodarone and desethylamiodarone concentrations were measured at the time
      of defibrillation energy requirement determination. The mean defibrillation
      energy requirement before amiodarone therapy was 9.9 +/- 4.6 J. After initiation
      of amiodarone therapy, the mean defibrillation energy requirement increased to
      13.7 +/- 5.6 J (P = 0.004). A linear relationship between the amiodarone (P =
      0.02, r = 0.6), desethylamiodarone (P = 0.02, r = 0.6), and combined amiodarone
      desethylamiodarone concentrations (P = 0.01, r = 0.6) and the defibrillation
      energy requirement was noted. Stepwise regression analysis demonstrated that the
      combined amiodarone-desethylamiodarone concentration was the only independent
      predictor of increase in the defibrillation energy requirement. CONCLUSION:
      Chronic oral amiodarone therapy increases the defibrillation energy requirement
      by approximately 62% in patients with an implantable defibrillator. The combined
      amiodarone-desethylamiodarone concentration is directly related to the increase
      in the defibrillation energy requirement.

PMID- 10921790
TI  - Amiodarone and defibrillation thresholds: a clinical conundrum.

PMID- 10921791
TI  - Atrial tachycardias originating from the atrial septum: electrophysiologic
      characteristics and radiofrequency ablation.
AB  - INTRODUCTION: The characteristics of atrial tachycardia (AT) have varied widely
      among different reports. The anatomic locations of ATs may bias the results. We
      propose that septal ATs and free-wall ATs have different characteristics. METHODS
      AND RESULTS: One hundred forty-one patients with AT underwent
      electropharmacologic study, endocardial mapping, and radiofrequency ablation.
      Forty-nine (34.7%) patients had septal AT originating from the anteroseptal, mid
      septal, and posteroseptal areas. Tachycardia cycle length was similar between
      septal AT and free-wall AT (367 +/- 46 msec vs 366 +/- 58 msec, P > 0.05). More
      patients with septal AT required isoproterenol to facilitate induction (44.9% vs
      31.5%, P <.0.05). Septal AT was more sensitive to adenosine than free-wall AT
      (84.4% vs 67.8%, P < 0.05). Only posteroseptal AT showed a positive P wave in
      lead V1 and negative P wave in all the inferior leads (II, III, aVF).
      Radiofrequency catheter ablation had a comparable success rate for septal AT and
      free-wall AT (96% vs 95%) without impairment of AV conduction. During follow-up
      of 49 +/- 13 months (range 17 to 85), the recurrence rate was similar for septal
      AT and free-wall AT (3.2% vs 4.6%, P = 0.08). CONCLUSION: Septal AT has
      electrophysiologic characteristics that are distinct from those of free-wall AT.
      Catheter ablation of the septal AT is safe and effective.

PMID- 10921792
TI  - Predicting the arrhythmogenic foci of atrial fibrillation before atrial
      transseptal procedure: implication for catheter ablation.
AB  - INTRODUCTION: Use of endocardial atrial activation sequences from recording
      catheters in the right atrium, His bundle, and coronary sinus to predict the
      location of initiating foci of atrial fibrillation (AF) before an atrial
      transseptal procedure has not been reported. The purpose of the present study was
      to develop an algorithm using endocardial atrial activation sequences to predict
      the location of initiating foci of AF before transseptal procedure. METHODS AND
      RESULTS: Seventy-five patients (60 men and 15 women, age 68 +/- 12 years) with
      frequent episodes of paroxysmal AF were referred for radiofrequency ablation. By
      retrospective analysis, characteristics of the endocardial atrial activation
      sequences of right atrial, His-bundle, and coronary sinus catheters from the
      initial 37 patients were correlated with the location of initiating foci of AF,
      which were confirmed by successful ablation. The endocardial atrial activation
      sequences of the other 38 patients were evaluated prospectively to predict the
      location of initiating foci of AF before transseptal procedure using the
      algorithm derived from the retrospective analysis. Accuracy of the value <0 msec
      (obtained by subtracting the time interval between high right atrium and His
      bundle atrial activation during atrial premature beats from that obtained during
      sinus rhythm) for discriminating the superior vena cava or upper portion of the
      crista terminalis from the pulmonary vein (PV) foci was 100%. When the interval
      between atrial activation of ostial and distal pairs of the coronary sinus
      catheter of the atrial premature beats was <0 msec, the accuracy for
      discriminating left PV foci from right PV foci was 92% in the 24 foci from the
      left PVs and 100% in the 19 foci from the right PVs. CONCLUSION: Endocardial
      atrial activation sequences from right atrial, His-bundle, and coronary sinus
      catheters can accurately predict the location of initiating foci of AF before
      transseptal procedure. This may facilitate mapping and radiofrequency ablation of
      paroxysmal AF.

PMID- 10921793
TI  - Radiofrequency catheter ablation for atrial fibrillation.

PMID- 10921794
TI  - Three-dimensional mapping of spontaneous ventricular arrhythmias in a canine
      thrombotic coronary occlusion model.
AB  - INTRODUCTION: Ventricular tachycardia (VT) and ventricular fibrillation (VF)
      induced by thrombotic coronary occlusion were mapped in three dimensions in ten
      dogs. METHODS AND RESULTS: Thrombotic occlusion was induced using a wire to
      deliver current to the proximal left circumflex artery (LCX). In nine dogs,
      nonsustained VT (NSVT) arose from numerous focal sites. Sustained VT was
      initiated in six dogs (VT group) by a focus near or in the ischemic region. VT
      was maintained by a focus in the ischemic border in three dogs and by
      macroreentry that involved both the ischemic and nonischemic regions in the other
      three dogs. In five dogs, VT degenerated into VF due to intramural reentry in
      different locations. Mean total activation time (AT), the time for activation to
      traverse the ventricles, for a sinus beat when LCX current was first applied was
      40 +/- 4 msec. In the four dogs in which VT occurred 3 to 7 minutes after total
      occlusion, sinus AT increased to 98 to 146 msec just before VT. Sinus AT in the
      four dogs without VT was always <98 msec. Mean AT of the first ten cycles of VT
      was significantly longer in those VTs that degenerated into VF (169 +/- 29 msec)
      than in those that did not (81 +/- 12 msec). CONCLUSION: Thrombotic LCX occlusion
      induced NSVT in 90%, VT in 60%, and VF in 50% of dogs. Focal mechanisms caused
      most NSVTs and VT initiation. VT was maintained by a focus near or in the
      ischemic region or by macroreentry involving both the ischemic and nonischemic
      regions. AT identified animals in which VT occurred soon after LCX occlusion and
      in which VT progressed to VF.

PMID- 10921796
TI  - Success and failure of the defibrillation shock: insights from a simulation
      study.
AB  - INTRODUCTION: This simulation study presents a further inquiry into the
      mechanisms by which a strong electric shock fails to halt life-threatening
      cardiac arrhythmias. METHODS AND RESULTS: The research uses a model of the
      defibrillation process that represents a sheet of myocardium as a bidomain. The
      tissue consists of nonuniformly curved fibers in which spiral wave reentry is
      initiated. Monophasic defibrillation shocks are delivered via two line electrodes
      that occupy opposite tissue boundaries. In some simulation experiments, the
      polarity of the shock is reversed. Electrical activity in the sheet is compared
      for failed and successful shocks under controlled conditions. The maps of
      transmembrane potential and activation times calculated during and after the
      shock demonstrate that weak shocks fail to terminate the reentrant activity via
      two major mechanisms. As compared with strong shocks, weak shocks result in (1)
      smaller extension of refractoriness in the areas depolarized by the shock, and
      (2) slower or incomplete activation of the excitable gap created by deexcitation
      of the negatively polarized areas. In its turn, mechanism 2 is associated with
      one or more of the following events: (a) lack of some break excitations, (b)
      latency in the occurrence of the break excitations, and (c) slower propagation
      through deexcited areas. Reversal of shock polarity results in a change of the
      extent of the regions of deexcitation, and thus, in a change in defibrillation
      threshold. CONCLUSION: The results of this study indicate the paramount
      importance of shock-induced deexcitation in both defibrillation and postshock
      arrhythmogenesis.

PMID- 10921795
TI  - Temporal organization of atrial activity and irregular ventricular rhythm during
      spontaneous atrial fibrillation: an in vivo study in the horse.
AB  - INTRODUCTION: Atrial fibrillation (AF) is common in healthy horses. We studied
      the temporal organization of AF to test the hypothesis that the arrhythmia is
      governed by a high degree of periodicity and therefore is not random in the
      horse. Further, we surmised that concealed conduction of AF impulses in the AV
      node results in an inverse relationship between AF frequency and ventricular
      frequency. METHODS AND RESULTS: Fast Fourier transform (FFT) analysis of atrial
      activity was done on signal-averaged ECGs (n = 11) and atrial electrograms (n =
      3) of horses with AF at control (C), after quinidine sulfate (22 mg/kg by mouth
      every 2 hours) at 50% time to conversion (T50), and immediately before conversion
      (T90) to sinus rhythm. FFT always revealed a single dominant frequency peak. The
      mean dominant frequency decreased until conversion (C = 6.84 +/- 0.85 Hz, T50 =
      4.87 +/- 1.5 Hz, T90 = 3.41 +/- 1.18 Hz; P < 0.001). Mean AA intervals (n = 500)
      gradually increased after quinidine. Mean RR intervals (n = 500), standard
      deviation of the mean (SDM), Poincare plots, and serial autocorrelograms (SACs)
      of 500 RR intervals were measured at C and T90 to determine the ventricular
      response to AF and quinidine-induced changes in the variability of the
      ventricular response. Mean RR interval and SDM were reduced after quinidine (C =
      1431 +/- 266 msec and 695 +/- 23 msec; T90 = 974 +/- 116 msec and 273 +/- 158
      msec, respectively; P < 0.01). Poincare plots and SAC at C and at T90 revealed a
      significant correlation of consecutive RR intervals typical of a system with a
      deterministic behavior. At T90, the variability of RR intervals was reduced and
      the overall periodicity of RR intervals was increased after quinidine
      administration. CONCLUSION: In the horse, AF is a complex arrhythmia
      characterized by a high degree of underlying periodicity. The inverse AA-to-RR
      interval relationship and reduced variability of RR intervals after quinidine
      suggest that the ventricular response during AF results from rate-dependent
      concealment of AF wavelets bombarding the AV node, which nevertheless results in
      a significant degree of short-term predictability of beat-to-beat changes in RR
      intervals.

PMID- 10921797
TI  - Existence of bistability and correlation with arrhythmogenesis in paced sheep
      atria.
AB  - INTRODUCTION: Studies of the electrical dynamics of cardiac tissue are important
      for understanding the mechanisms of arrhythmias. This study uses high-frequency
      pacing to investigate the dynamics of sheep atria. METHODS AND RESULTS: A 504
      electrode mapping plaque was affixed to the right atrium in six sheep. Cathodal
      pacing stimuli were delivered to the center of the plaque. Pacing period (Tp) was
      decreased from 275 +/- 25 msec to 75 +/- 25 msec and then increased to 230 +/- 70
      msec in steps of either 5 or 10 msec. In all 21 trials in six sheep, the atrium
      responded 1:1 at longer Tps and 2:1 at shorter Tps. As Tp was decreased, the
      response switched to 2:1 at a particular Tp. Conversely, as Tp was increased, the
      response switched back to 1:1 at a particular Tp. Over 21 trials, the 1:1-to-2:1
      and 2:1-to-1:1 transitions occurred at 119.5 +/- 18.8 msec and 130.0 +/- 19.1
      msec, respectively. This hysteretic behavior yielded bistability windows, 10.5 +/
      7.2 msec wide, wherein 1:1 and 2:1 responses existed at the same Tp. In 15
      trials and in all animals, idiopathic wavefronts emanating from outside the
      mapped region passed through the mapped region. In 13 of those trials, the
      idiopathic wavefronts occurred at Tps within the bistability window or within 35
      msec of its upper or lower limit. CONCLUSION: Bistability windows and idiopathic
      wavefronts were observed and found to be correlated with each other, suggesting a
      connection between bistability and arrhythmogenesis.

PMID- 10921798
TI  - A patient with "atrial torsades de pointes".
AB  - A patient with long QT syndrome and a history of palpitations underwent
      electrophysiologic study. Runs of polymorphic self-terminating atrial
      tachyarrhythmias were easily induced and occurred spontaneously several times.
      Atrial monophasic action potential (MAP) durations were prolonged at short pacing
      cycle lengths. Premature high right atrial extrastimuli prolonged MAP durations
      in the low right atrium, resulting in an inverse electrical restitution curve,
      and increased dispersion of repolarization. MAP morphology showed gradually
      increasing early afterdepolarizations. When the arrhythmia was initiated, a new
      action potential reproducibly emerged from these afterdepolarizations. To the
      knowledge of the authors, this is the first reported case of "atrial torsades de
      pointes" in a patient.

PMID- 10921799
TI  - Atrioventricular nodal tachycardia occurring during atrial fibrillation.
AB  - We describe the case of a 32-year-old woman with palpitations and atrial
      fibrillation (AF) as the only documented arrhythmia. The patient underwent
      electrophysiologic study and was found to have inducible AV nodal reentrant
      tachycardia (AVNRT). During a prolonged episode of AVNRT, AF developed in both
      atria, but AVNRT persisted. Dissociation of the atria during AVNRT is evidence
      that the atrium is not necessary in AVNRT. This case also illustrates the utility
      of an electrophysiologic study in locating a potentially curable arrhythmia as
      the primary cause of AF in young patients.

PMID- 10921800
TI  - Atrial fibrillation and the subatrial location of the atrioventricular nodal
      reentrant circuit: adding a new piece to an old puzzle.

PMID- 10921801
TI  - Long QT syndrome: biophysical and pharmacologic mechanisms in LQT3.
AB  - The congenital long QT syndromes (LQTSs) are a group of inherited cardiac
      disorders that increase the risk of sudden death from ventricular arrhythmias.
      Individuals with LQTS show abnormalities in cardiac repolarization. Mutations
      that cause LQTSs are distributed throughout the human genome on chromosomes 3, 4,
      7, 11, and 21. Recent molecular genetic studies established that LQT3 results
      from mutations in the cardiac sodium ion channel gene (SCN5A). Research efforts
      are aimed at elucidating molecular mechanisms, determining the links between
      clinical phenotypes and the individual gene mutations, and pharmacologic
      targeting of the phenotypes. This approach will ultimately guide rational
      therapy. In addition, LQT3 serves as a model for inherited molecular-based
      disorders, as well as a paradigm for understanding the genesis and control of
      other cardiac arrhythmias.

PMID- 10921802
TI  - Postoperative tachycardia with a P wave identical to that of sinus rhythm: what
      is tachycardia mechanism?

PMID- 10921803
TI  - Adenosine-induced atrial fibrillation.

PMID- 10921804
TI  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy: need for an
      international registry. European Society of Cardiology and the Scientific Council
      on Cardiomyopathies of the World Heart Federation.
AB  - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a heart
      muscle disease characterized by peculiar right ventricular involvement and
      electrical instability that precipitates ventricular arrhythmias and sudden
      death. The purpose of the present consensus report of the Study Group of the
      European Society of Cardiology and the Scientific Council on Cardiomyopathies of
      the World Heart Federation is to review the considerable progress in our
      understanding of the etiopathogenesis, morbid anatomy, and clinical presentation
      of ARVD/C since its first description in 1977. This article will focus on the
      important but still unanswered issues, mostly regarding risk stratification,
      clinical outcome, and management of affected patients. Because ARVD/C is
      relatively uncommon and any one center may have experience with only a few
      patients, an international registry is being established to accumulate
      information and enhance the numbers of patients that can be analyzed to answer
      the pending questions. The registry also will facilitate pathologic, molecular,
      and genetics research on the etiology and pathogenesis of the disease.
      Furthermore, availability of an international database will enhance awareness of
      this largely unrecognized condition among the medical community. Physicians are
      encouraged to enroll patients in the International Registry of ARVD/C.

PMID- 10921806
TI  - bestbets.org: odds on favourite for evidence in emergency medicine reaches the
      world wide web.

PMID- 10921805
TI  - On Brody effect and increase in QRS amplitude.

PMID- 10921807
TI  - Chest pain evaluation units.

PMID- 10921808
TI  - Migraine: pharmacotherapy in the emergency department.
AB  - Migraine can be a disabling condition for the sufferer. For the small number of
      patients who fail home therapy and seek treatment in an emergency department,
      there are a number of therapeutic options. This paper reviews the evidence
      regarding the effectiveness and safety of the following therapies: the
      phenothiazines, lignocaine (lidocaine), ketorolac, the ergot alkaloids,
      metoclopramide, the "triptans", haloperidol, pethidine and magnesium. Based on
      available evidence, the most effective agents seem to be prochlorperazine,
      chlorpromazine and sumatriptan, each of which have achieved greater then 70%
      efficacy in a number of studies.

PMID- 10921809
TI  - Communication skills training for emergency department senior house officers--a
      qualitative study.
AB  - OBJECTIVE: To identify common weaknesses in senior house officer-patient
      consultation skills, and evaluate direct observation with feedback and
      negotiation of educational contracts, as a teaching tool in an emergency
      department setting. METHOD: Common weaknesses were identified through review of
      feedback charts by three trained observers. Alteration in clinical and learning
      behaviour, as well as senior house officer and observer perceptions of the
      teaching were evaluated qualitatively by a combination of semistructured
      interviews and focus groups. RESULTS: Several common weaknesses were identified,
      notably the use of closed questions, and poor negotiation and explanation of
      treatment plan and follow up. The senior house officers perceived improvement in
      their clinical practice, welcomed feedback, and subsequently set, though did not
      complete educational contracts. While comfortable with this style of teaching,
      the observers felt that it did not make efficient use of teaching time.
      CONCLUSIONS: This study identifies common weaknesses in the consultation skills
      of emergency department senior house officers and confirms the need for training
      in this area. Direct observation is effective in changing behaviour to this end,
      though self directed learning is not necessarily stimulated. Video recorded
      consultations with group feedback may be a more effective teaching tool.

PMID- 10921810
TI  - Can communication skills workshops for emergency department doctors improve
      patient satisfaction?
AB  - OBJECTIVE: To assess whether the attending of the communication skills workshops
      by the emergency department doctors improves patient satisfaction and reduces the
      number of complaints on doctors' attitude. METHOD: Standard performas were sent
      to all emergency departments (EDs) in Hong Kong soliciting their numbers of
      written complaints on doctors' attitude or communication problems during the nine
      months before and after a series of communication skills workshops. Patient
      satisfaction surveys in four representative EDs, before and after the workshops,
      were collected and the satisfaction rates of doctors' attitude, explanation and
      advice were subsequently compared. RESULTS: For the hospitals that responded,
      written complaints against doctors' attitude reduced from 26 (1 January 1995 to
      30 September 1995) to 15 (1 July 1996 to 31 March 1997), amounting to a 42%
      reduction despite an increase of attendance from 724000 to 898000 (p = 0.05
      chi2). From the 663 and 480 questionnaires collected before and after the
      workshops respectively, the satisfaction rate to doctors' attitude increases from
      88.3% before to 98% after the workshops, while the satisfaction rate to
      explanation and advice provided by doctors increases from 79.8% to 93.8%.
      CONCLUSION: Communication skills workshops in Hong Kong can improve ED doctors
      communication skills with a corresponding increase in patient satisfaction and
      reduction of complaints against ED doctors.

PMID- 10921811
TI  - Evaluating the use of computerised clinical guidelines in the accident and
      emergency department.
AB  - OBJECTIVES: To investigate the pattern and frequency of use of computerised
      clinical guidelines (CCG) in an accident and emergency department. METHODS: A
      software program was written to record information on a central database each
      time the CCG were used. Data were collected prospectively for a six month period.
      Users were blind to the study. The date, time of use and guidelines consulted
      were recorded. RESULTS: 1974 individual sessions were logged comprising of 10204
      "hits". The CCG were used for a median of 10 sessions per day (range 1-38, SD
      5.49). A median of three subjects were accessed during each session (range 1-39,
      SD 5). The CCG were used most often during peak daily activity; 11 am (609 hits),
      5 pm (678 hits) and 12 pm (604 hits) and on Sundays (1875 hits), Thursdays (1770
      hits) and Saturdays (1608 hits). The most frequently used guidelines concerned
      orthopaedics and fracture management (1590 hits), wound care (546 hits),
      poisoning (473 hits), medical emergencies (267 hits) and radiological policy (148
      hits). CONCLUSIONS: In this department CCG have become easily integrated as part
      of normal day to day working practice. The CCG are accessible 24 hours a day.
      They can also be easily updated according to best evidence, local policy or
      national guidelines. The results of this study have helped the authors to focus
      education to areas of clinical need.

PMID- 10921812
TI  - A standardised neurosurgical referral letter for the inter-hospital transfer of
      head injured patients.
AB  - OBJECTIVES: (1) To evaluate the use of a standardised neurosurgical referral
      letter in terms of compliance, completeness and clinical relevance. (2) To
      compare the clinical information provided on the standardised neurosurgical
      letter with that provided by referring hospitals that used alternative
      documentation. DESIGN: A six month prospective audit was conducted in south west
      Scotland. Consultant neurosurgeons were asked to weight key clinical variables on
      the neurosurgical referral letter (NRL). Postal surveys of 114 referring accident
      and emergency (A&E) staff and 18 neurosurgical receiving staff were undertaken to
      determine the clinical relevance of the NRL. Case notes were examined for the
      presence and level of completeness of the NRL. In the absence of the NRL, a form
      was completed retrospectively using data from the referring hospital's letter.
      This enabled comparison of the NRL with routine hospital letters in terms of the
      availability of key clinical information. RESULTS: 139 adult patients were
      identified as suitable for inclusion: 99 patients were transferred from 11
      hospitals with access to the NRL. The compliance rate for use of the NRLwas 82%.
      Forty patients were transferred from nine hospitals that did not have access to
      the NRL. The completion rate of key variables on the NRL was higher than when an
      ordinary letter was sent: 87% compared with 38%. The NRL was considered useful by
      67 of 71 (94%) A&E questionnaire respondents and by 14 of 15 neurosurgeons who
      responded. CONCLUSIONS: The widespread acceptance of the NRL and its ability to
      provide essential clinical information in a concise format not available in
      routine hospital letters indicates that national, standardised documentation can
      be implemented if users are involved in both its design and implementation.

PMID- 10921814
TI  - Pain in young children attending an accident and emergency department.
AB  - OBJECTIVES: To assess pain in young children presenting to an accident and
      emergency (A&E) department. To evaluate the use of the toddler-preschooler
      postoperative pain scale (TPPPS) and the use of analgesia in these children.
      METHODS: 100 children aged 1-5 years presenting to an A&E department were
      assessed for pain. Pain assessments were carried out using a modified form of the
      TPPPS; a visual analogue scale by parents and a numerical scale by nursing staff.
      RESULTS: The majority of children were assessed as having pain: 60 by the TPPPS,
      58 by the nurses and 63 by parents. Only 30 children, however, received
      analgesia. Children with the highest pain scores as assessed by nursing staff or
      using the TPPPS all received analgesia. CONCLUSIONS: The pain scale appears
      suitable for use in young children in A&E departments. The subsequent management
      of pain in young children could be improved.

PMID- 10921813
TI  - A comparison of the efficacy and safety of morphine and pethidine as analgesia
      for suspected renal colic in the emergency setting.
AB  - OBJECTIVES: The aim of this study was to compare morphine and pethidine in
      patients with clinically suspected renal colic with regard to analgesic efficacy,
      patient satisfaction and side effects. METHODS: double blinded, randomised
      controlled trial. RESULTS: There was no significant difference between morphine
      and pethidine with respect to any of the parameters measured. CONCLUSION: Because
      of the well known adverse effects that may be associated with pethidine use, the
      authors recommend that morphine should be the preferred agent in suspected renal
      colic, when an opioid analgesic is to be used.

PMID- 10921815
TI  - Why do children vomit after minor head injury?
AB  - OBJECTIVE: To determine factors associated with vomiting after minor head injury
      in a paediatric population with the intention of defining the role of vomiting in
      management decisions. METHODS: A prospective study of all patients presenting
      with minor head injury to the Royal Hospital for Sick Children, Edinburgh,
      between 1 May and 30 June 1997. Information regarding basic demographics,
      features of the head injury and past and family history was noted on a proforma.
      This included mechanism of injury, site of impact, presence or absence of scalp
      haematoma, skull fracture or brain injury and intrinsic factors such as age,
      family history of migraine and a personal history of migraine, its childhood
      variants and associated conditions. The relation between vomiting and these
      features was analysed using chi2 and Fisher's exact tests. RESULTS: 563 children
      aged from birth to 13 years presented with minor head injury. Complete data were
      obtained on 463 patients. Some 15.8% vomited after minor head injury. Comparing
      vomiters with non-vomiters the only associated factors that could be identified
      were a past history of recurrent vomiting or motion sickness (p= 0.0035, p=0.036
      respectively). CONCLUSIONS: Vomiting after minor head injury seems to be related
      to individual intrinsic factors rather than specific features of the head injury
      and its role in management decisions needs to be explored further.

PMID- 10921816
TI  - Drug related deaths in the community: a preventive role for accident and
      emergency departments?
AB  - Reducing drug related deaths has been identified as a priority by the British
      government. This study examined the link between drug related deaths in the
      community and prior contact with local accident and emergency (A&E) services.
      Most drug related deaths were found among male opioid users in their early 30s
      who had previously attended the local A&E department. It is suggested that A&E
      departments have a vital part to play, not only in the acute management but also
      in the prevention of drug related deaths in the community. Models for primary
      prevention, liaison and ongoing referral are discussed.

PMID- 10921817
TI  - An introduction to everyday statistics--2.

PMID- 10921818
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Ingested coins and metal detection.

PMID- 10921819
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Regional anaesthesia for femoral shaft fractures in children.

PMID- 10921820
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Activated charcoal in paracetamol overdose.

PMID- 10921821
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Management of uncomplicated soft tissue gunshot wounds.

PMID- 10921822
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Repair of partial lacerations of the extensor tendons of the hand.

PMID- 10921823
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Early management of displaced nasal fractures.

PMID- 10921824
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Antibiotics in base of skull fractures.

PMID- 10921825
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Glucose or glucagon for hypoglycaemia.

PMID- 10921826
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Closure of pretibial lacerations.

PMID- 10921827
TI  - Towards evidence based emergency medicine: best BETs from the Manchester Royal
      Infirmary. Digital or metacarpal block for finger injuries.

PMID- 10921828
TI  - Primary care outcomes in patients treated by nurse practitioners or physicians. A
      randomized trial.

PMID- 10921829
TI  - Anaesthetic training in accident and emergency.

PMID- 10921830
TI  - Rapid sequence intubation.

PMID- 10921831
TI  - High level simulator.

PMID- 10921832
TI  - Emergency cranial computed tomography.

PMID- 10921833
TI  - The irritable hip.

PMID- 10921834
TI  - Topical anaesthesia use in the management of children's lacerations, a postal
      survey.

PMID- 10921835
TI  - Feigning dystonia to feed an unusual drug addiction.

PMID- 10921836
TI  - Real-time RT-PCR fluorescent detection of tomato spotted wilt virus.
AB  - A real-time reverse transcription-polymerase chain reaction assay based on TaqMan
      chemistry was developed for the detection and quantification of tomato spotted
      wilt virus (TSWV). This method enabled sensitive, reproducible and specific
      detection of TSWV in 'leaf soak' and total RNA extracts from infected plants.
      TaqMan reliably detected TSWV in as little as 500 fg total RNA. The assay was 10
      fold more sensitive than visualisation of ethidium bromide-stained bands
      following agarose gel electrophoresis. TSWV isolates from various crops and
      locations were detected with a cycle threshold of 20-26 in 1 ng total RNA
      extracted from fresh or freeze-dried leaves. A dilution series of in vitro
      transcripts from a cloned 628 base pair fragment of TSWV S RNA served as standard
      for quantification of viral template in infected leaf samples. The TaqMan assay
      detected reproducibly 1000 molecules of the target transcript.

PMID- 10921837
TI  - Using a panel of monoclonal antibodies to detect Maedi virus (MV) in chronic
      pulmonary distress of sheep.
AB  - A selected panel of six monoclonal antibodies (mAbs) against Maedi-Visna virus
      (MVV), recognising the core proteins (p27 and p15) and the envelope protein
      (gp105) of MVV, was tested using different unmasking techniques on paraffin
      embedded lung samples of a seropositive sheep. Only three mAbs were chosen,
      according to their strong reactivity. mAbs 1A7, 1B6 and 4B3 were employed in an
      immunohistochemical trial focused on the diagnosis of the lungs of 26 sheep with
      progressive pulmonary distress. These mAbs demonstrated MVV in 21 out of 26 cases
      including lymphoid interstitial pneumonia (LIP) and pulmonary adenomatosis. In
      only nine cases did all three mAbs react positively with the same sample. The
      sensitivity of immunohistochemical diagnosis of Maedi pneumonia can be increased
      by using mAbs 1A7, 4B3 and 1B6 together; that is a panel of mAbs direct against
      the envelope (gp105) and capsid (p27) viral proteins. The positive signal was
      focal and confined to the cytoplasm of bronchoalveolar epithelial cells and
      alveolar-interstitial macrophages. The results suggest that this panel of mAbs is
      useful to confirm severe LIP lesions such as Maedi pneumonia, to demonstrate
      Maedi infections in mild LIP, to demonstrate MVV in mixed pulmonary changes, and
      to investigate the pathogenesis of Maedi-Visna.

PMID- 10921838
TI  - A comprehensive systematic approach to identification of influenza A virus
      genotype using RT-PCR and RFLP.
AB  - Amplification of influenza A virus gene segments by reverse transcription
      polymerase chain reaction (RT-PCR) can be combined with enzymatic digestion to
      reveal unique restriction fragment length polymorphisms specific for H1N1 and
      H3N2 subtype viruses. We have used the method to provide a rapid, specific and
      reproducible identification of the genotype of high-growth influenza reassortants
      derived from A/Puerto Rico/8/34 (PR8). Digestion of the gene segments amplified
      from wild-type viruses, PR8 and reassortants at sites unique to either the wild
      type strain or to PR8 provided positive, unambiguous identification of the origin
      of each of the internal genes, and distinguished the internal genes of both H1N1
      and H3N2 strains from those of PR8. This method has also permitted us to quickly
      confirm that reassorting has occurred and to optimize the selection of
      reassortant clones with maximum number of PR8 internal genes. Since the method
      can detect 1-10% of a second strain in a mixed population, the method can also be
      used to detect samples containing more than one viral subtype and to assess the
      purity of influenza viruses used for manufacturing vaccines.

PMID- 10921839
TI  - Differentiation of citrus tristeza virus isolates by serological analysis of p25
      coat protein peptide maps.
AB  - A procedure was developed to purify rapidly and easily a sufficient quantity of
      native p25 coat protein (CP) to allow comparison of five isolates of citrus
      tristeza virus (CTV) by serological analysis of peptide maps, using monoclonal
      and polyclonal antibodies. CTV particles were concentrated by centrifugation and
      purified by agarose gel electrophoresis. The CP was extracted from gel slices
      riched in virions and protein yields were about three times greater than those
      obtained previously and of comparable purity. The purified CP was partially
      digested with either V8 or papain endo-protease, and the peptides generated were
      separated and electroblotted to a membrane. Protein blots were tested with four
      monoclonal antibodies and one source of polyclonal antibodies. The serological
      maps generated by papain allowed differentiation of all the isolates examined,
      and those generated by V8 endoprotease allowed discrimination of four of the five
      isolates tested. Some of these isolates had been indistinguishable based on their
      reactivity in DASI-ELISA, dsRNA pattern and biological characterization.
      Serological analysis of peptide maps, as described below, allowed accurate
      comparison of CTV isolates with minimum amounts of p25 CP and proved superior to
      other techniques for discriminating CTV isolates.

PMID- 10921840
TI  - Green fluorescent protein as a probe of rotational mobility within bacteriophage
      T4.
AB  - Green fluorescent protein (GFP) was targeted into bacteriophage T4 heads and
      proheads as a probe of the internal environment. Targeting was accomplished with
      internal protein III (IPIII) fusion proteins or capsid targeting sequence (CTS)
      tagged proteins, where CTS is the 10-amino acid residue CTS of IPIII. Recombinant
      phage T4[CTS/IPIII/GFP], T4[CTS/IPIII(T)GFP], and T4[CTS/GFP] packaged GFP fusion
      proteins and processed them at cleavage sites designated /. Steady-state and time
      resolved fluorescence measurements suggest that packaged GFP is concentrated to a
      high density, that fusion protein IPIII(T)GFP occurs in a tightly clustered
      arrangement, and that the internal milieu of the phage head reduces rotational
      mobility of GFP. Phage, but not proheads, packaged with fusion protein
      IPIII(T)GFP gave an unexpectedly lower anisotropy than phage and proheads
      packaged with GFP, which suggests IPIII(T)GFP is bound to DNA in a manner that
      causes close associations between GFP molecules resulting in homotransfer between
      fluorophores within packaged phage. Targeting of reporter proteins into active
      virions is a promising approach for determining the structure of the condensed
      DNA, and properties of encapsidated viral enzymes.

PMID- 10921841
TI  - Development of a PCR procedure for the detection of a herpes-like virus infecting
      oysters in France.
AB  - A PCR-based procedure for detecting a herpes-like virus that infects the Japanese
      oyster, Crassostrea gigas, in France was developed. Two primers were designed to
      provide specific amplification products ranging in size from 917 to 1001 bp when
      carried out on oyster herpes-like virus DNA. No amplification was observed of
      oyster genomic DNA nor of the DNA from vertebrate herpesviruses. Crude samples
      were prepared and submitted to nested PCR, allowing amplification of DNA
      fragments of the expected size when carried out on infected larval and spat
      samples. The procedure used to prepare the sample for PCR was found to be
      critical because of the presence of unidentified substances in oyster tissues
      that inhibit the PCR reaction. A rapid and convenient sample preparation using
      ground tissues allowed a sensitive detection of the herpes-like virus infected
      oysters. The ability of the defined PCR protocol to diagnose herpes-like virus
      infections in oysters was compared to the transmission electron microscopy
      technique using 15 C. gigas larval batches with or without mortalities. PCR
      amplification is as sensitive a diagnostic assay for herpes-like virus as
      transmission electron microscopy. However, the nested PCR protocol is more
      convenient and less time consuming. The relationship between reported mortalities
      among C. gigas oyster spat and herpes-like virus DNA detection by PCR was also
      investigated. Statistical analysis showed that virus detection and mortalities
      are correlated. This observation highlights the importance of studying the
      causative role of herpes-like virus in oyster spat mortalities.

PMID- 10921842
TI  - Quantitation of polyomavirus DNA by a competitive nested polymerase chain
      reaction.
AB  - A new method to quantitate small amounts of DNA in clinical specimens is
      described. The method, a nested competitive polymerase chain reaction (ncPCR), is
      able to quantitate between 10 and 10(6) copies per tube of polyomavirus DNA and
      shows good reproducibility when clinical samples are analysed. Throughout the
      whole procedure, an internal standard (IS) competes for the primers with the
      target DNA. The internal standard, a heterologous sequence containing the four
      primer recognition sites, was constructed using a modification of the 'MIMIC'
      approach that is useful for obtaining competitor sequences for any viral,
      bacterial or eukaryotic target. The ncPCR method for polyomavirus was applied to
      cerebrospinal fluids (CSF) from AIDS patients with progressive multifocal
      leukoencephalopathy (PML) and urine specimens from bone marrow transplant
      patients affected by haemorrhagic cystitis. The results obtained suggest that the
      ncPCR method is a sensitive and useful method for quantitating genomic load in
      clinical samples.

PMID- 10921843
TI  - A highly specific and sensitive sandwich blocking ELISA based on baculovirus
      expressed pseudorabies virus glycoprotein B.
AB  - A direct sandwich blocking enzyme-linked immunosorbent assay (BacgB ELISA) based
      on the reaction between a monoclonal antibody (MAb) and a recombinant
      glycoprotein B (gB) of pseudorabies virus (PRV) was developed. This protein was
      obtained in large quantities from insect cells infected with a PRV gB recombinant
      baculovirus. Expression of the gB was confirmed by immunoperoxidase monolayer
      assay (IPMA) with gB specific MAbs. The specificity and sensitivity of the
      developed BacgB ELISA were evaluated and compared with two commercially available
      tests by using sets of sera of known PRV infection or vaccination history. For
      validation, 347 serum samples have been tested. The BacgB ELISA had a high
      sensitivity and specificity, which were comparable with those of the two
      commercial tests. In addition, the BacgB ELISA allows detecting anti-gB
      antibodies in pig serum as early as 7 days following infection. Also maternal
      antibodies in uninfected pig sera were detected. We conclude that the BacgB ELISA
      is a useful tool for the detection of as well vaccinated as infected pigs
      (including derivatives from gE negative vaccine strains), with the added
      advantage that it uses an antigen that can be produced safely and in large
      quantities.

PMID- 10921844
TI  - A polymerase chain reaction method for the amplification of full-length envelope
      genes of HIV-1 from DNA samples containing single molecules of HIV-1 provirus.
AB  - Polymerase chain reaction (PCR) amplification of full-length envelope genes from
      the human immunodeficiency virus type 1 (HIV-1) directly from uncultured clinical
      samples is difficult. This paper describes a comparative assessment of the
      performance of three thermostable polymerases in an HIV-1 full-length envelope
      gene PCR. The PCR method utilising Expand HiFi polymerase was successful when
      using DNA samples extracted from a variety of sources including blood, semen and
      various tissues. This method generated high and specific yields of product from
      samples containing as little as one copy of HIV-1 proviral DNA. The resulting PCR
      products were suitable for a variety of downstream analytical methods including
      DNA sequence analysis.

PMID- 10921845
TI  - Development of a real-time quantitative RT-PCR for the detection of HIV-2 RNA in
      plasma.
AB  - An assay is described for the quantification of human immunodeficiency virus type
      2 (HIV-2) RNA in EDTA plasma based on RT-PCR using the Taqman real-time PCR
      detection method. As standard, an electron microscopically counted virus stock of
      HIV-2 strain NIHZ was used. The lower detection limit is 5 # 102 HIV-2 RNA copies
      per ml of EDTA plasma. The assay is linear within the range required (5 # 102-106
      HIV-2 RNA copies/ml of EDTA plasma) with an intra assay variability of 2.5% and
      an inter-assay variability ranging from 2% at 106 copies to 7.5% at the lower
      detection limit. Three primer/probe combinations were developed to circumvent
      false negative samples due to nucleotide variation in the target sequence. Using
      these primer/probe sets enabled the detection of HIV-2 DNA sequences from all HIV
      2 seropositive individuals and two out of five dual human immunodeficiency virus
      type 1 (HIV-1) and HIV-2 seropositive individuals visiting the University
      Hospital Rotterdam.

PMID- 10921846
TI  - Utilisation of bacteriophage display libraries to identify peptide sequences
      recognised by equine herpesvirus type 1 specific equine sera.
AB  - Three filamentous phage random peptide display libraries were used in biopanning
      experiments with purified IgG from the serum of a gnotobiotic foal infected with
      equine herpesvirus-1 (EHV-1) to enrich for epitopes binding to anti-EHV-1
      antibodies. The sequences of the amino acids displayed were aligned with protein
      sequences of EHV-1, thereby identifying a number of potential antibody binding
      regions. Presumptive epitopes were identified within the proteins encoded by
      genes 7 (DNA helicase/primase complex protein), 11 (tegument protein), 16
      (glycoprotein C), 41 (integral membrane protein), 70 (glycoprotein G), 71
      (envelope glycoprotein gp300), and 74 (glycoprotein E). Two groups of sequences,
      which aligned with either glycoprotein C (gC) or glycoprotein E (gE), identified
      type-specific epitopes which could be used to distinguish between sera from
      horses infected with either EHV-1 or EHV-4 in an ELISA using either the phage
      displaying the peptide or synthetic peptides as antigen. The gC epitope had been
      previously identified as an immunogenic region by conventional monoclonal
      antibody screening whereas the gE antibody binding region had not been previously
      identified. This demonstrates that screening of phage display peptide libraries
      with post-infection polyclonal sera is a suitable method for identifying
      diagnostic antigens for viral infections such as EHV-1.

PMID- 10921847
TI  - Rapid molecular epidemiologic studies of human parainfluenza viruses based on
      direct sequencing of amplified DNA from a multiplex RT-PCR assay.
AB  - Sequencing studies of limited regions of the human parainfluenza viruses (HPIVs)
      genomes have helped describe patterns of virus circulation and characterize
      institutional outbreaks of HPIVs-associated respiratory illness. In this study,
      we sequenced reverse transcription polymerase chain reaction (RT-PCR)-amplified
      HPIVs RNA obtained from a multiplex RT-PCR assay described previously for
      simultaneous detection of HPIV-1, 2 and 3. Differences in the nucleotide
      sequences of limited regions of the HN gene allowed us to distinguish temporally
      and geographically diverse HPIV isolates (43 HPIV-1, 7 HPIV-2, 12 HPIV-3 isolates
      from this and previously published studies). In addition, an outbreak of HPIV-3
      associated illness among infants on a pediatric ward was investigated by
      comparing sequences of three ward isolates with three matched community controls.
      Sequences of all ward isolates were identical and differed from those of the
      community controls, suggesting a single introduction and nosocomial transmission
      of the virus. Combining multiplex reverse transcription polymerase chain reaction
      (RT-PCR) assays with direct sequencing of the PCR products can provide an
      integrated system for rapid diagnosis and characterization of HPIVs.

PMID- 10921848
TI  - Direct detection of infectious HIV-1 in blood using a centrifugation-indicator
      cell assay.
AB  - Plasma HIV RNA is a useful surrogate marker for predicting HIV-1 disease
      progression in infected individuals but provides no information regarding the
      infectious viral titer. Traditional assays of infectious HIV-1 are, however, time
      consuming, insensitive, use non-standardized reagents and are subject to
      selection bias introduced by prolonged cultivation. In this pilot study
      infectious HIV-1 was detected directly in patient plasma using the indicator line
      HeLa-CD4-CCR5-LTR/beta-gal in a centrifugation-culture method. Replication
      competent HIV-1 was identified within 2 days of tissue culture inoculation in six
      (26%) of 23 plasma specimens. The capability of a new cell line, MT4-CCR5-tat, to
      amplify plasma HIV-1 was also tested. HIV was cultivated from ten (71%) of 14
      specimens using MT4-CCR5-tat cells before titering the virus with the indicator
      cell assay. Using these stable cell lines in refined versions of this assay it
      may be feasible to develop rapid, simple methods for titering infectious plasma
      HIV-1 and for testing the susceptibility of the virus to antiretroviral drugs.

PMID- 10921849
TI  - Electrochemical methods of evaluating the van't Hoff enthalpy in reactions
      involving biological macromolecules.
AB  - We highlight conditions under which coincidence of van't Hoff and calorimetric
      enthalpies can be experimentally verified for reactions of biochemical interest.
      First, we clarify that, often, chemical equations in condensed phase do not
      explicitly contain information on all processes involved. Second, we underline
      that the accuracy of electrochemical methods is much higher than that of other
      non-calorimetric techniques. Electrochemical data on the binding of ethidium ion
      to DNA are re-examined to verify that the entropy evaluated as the temperature
      derivative of the free energy agrees in full with the calorimetric one. Third, we
      point out that unfolding or self-association enthalpies of redox proteins can be
      reliably obtained by electromotive force measurements, taking advantage of their
      linkage to redox enthalpies. Thermodynamic cycles coupling biochemical
      transformations to redox systems are briefly discussed.

PMID- 10921850
TI  - Molecular weight and antitumour activity of Zymomonas mobilis levans.
AB  - Levans produced by several Zymomonas mobilis strains were classified by their
      viscosity average molecular weight and tested against sarcoma 180. Measurements
      of the samples' polydispersity were carried out to characterise the molecular
      weight distribution. The antitumour activities of levan samples were plotted
      against the viscosity average molecular weight and a maximum value of this
      activity was found at Mv = 210,000 (Mw = 456,900 and PD = 16.2). The results
      indicate that levan antitumour activities depend on the polysaccharide molecular
      weight and that a specific class of molecular weight may be responsible for this
      effect.

PMID- 10921851
TI  - Phase separation and gel formation in kinetically trapped gelatin/maltodextrin
      gels.
AB  - The kinetics of phase separation and gel formation of gelatin/maltodextrin
      mixtures have been studied using confocal laser scanning microscopy (CLSM),
      transmission electron microscopy (TEM), stereological image analysis and
      rheology. The quantified microstructural parameters were the volume-weighted mean
      volume and the interfacial area. The temperature of phase separation was defined
      as the temperature where the first signs of phase separation were observed in
      CLSM. The gelatin concentration varied between 4 (wt.) and 5% and the
      maltodextrin concentration varied between 2 and 6%. Maltodextrin was labelled
      covalently with RITC to improve the contrast between the gelatin phase and the
      maltodextrin phase. The solutions were cooled from 60 to 10 degrees C, and the
      cooling rates used were 0.4, 1 and 3 degrees C/min. All systems were found to be
      gelatin continuous under the experimental conditions used. The results showed
      that the temperature of phase separation (TPS) increased both with the gelatin
      concentration and the maltodextrin concentration, but particularly with the
      former. The size of the maltodextrin inclusions increased with TPS, and the
      interfacial area decreased with increasing TPS. The diameter of the maltodextrin
      inclusions varied between 1.6 and 8.5 microm at 1 degrees C/min. The size of the
      maltodextrin inclusions was found to increase with decreasing cooling rate and
      was largest at 0.4 degrees C/min. The TPS was compared with the gelation
      temperature (Tgel) at three different concentrations of gelatin and maltodextrin
      (4/3, 4/5, 5/5%). CLSM micrographs and TEM micrographs showed that these three
      concentrations of gelatin and maltodextrin had different microstructures. At a
      TPS above Tgel (5/5%), the phase separation proceeded faster than the gel
      formation and the microstructure had few, large maltodextrin inclusions and a
      clean continuous gelatin phase. At a TPS comparable with Tgel (4/5%), phase
      separation occurred during gel formation, which led to a varying microstructure
      and competition between the phase separation and the gel formation. At a TPS
      below Tgel (4/3%), gel formation proceeded faster than the phase separation and
      the microstructure had many, small inclusions and a diffuse microstructure, and
      the phase separation was incomplete. It was established that the microstructure
      was determined by the relative rates of the phase separation and the gel
      formation. Three different zones of phase separation could be distinguished based
      on comparisons of TPS and Tgel, and results from CLSM, TEM and image analysis.

PMID- 10921852
TI  - The fluorescent characterization of the polymerized microtubule-associated
      protein Tau.
AB  - A new fluorescence formed while microtubule-associated protein tau was incubated
      at 25 and 37C for hours, with its maximum excitation at 230 and 280 nm,
      respectively. The fluorescence completely formed after tau was incubated in
      phosphate buffer and Tris-HCl buffer for approximately 20 h, with a relaxation
      phase about 2-4 h. The light scattering of the sample solution improved during
      formation of the fluorescence when tau was incubated. Both the fluorescence and
      tau oligomers did not form when tau was incubated in the buffers containing DTT.
      On the other hand, heparin improved both tau aggregation and the fluorescence
      formation. It suggests that the fluorescence comes from tau polymerization, which
      may follow the mechanism of tyrosine-tyrosinate emission for a protein not
      containing any tryptophan residues. This new fluorescence could be used as a
      probe to tau polymers.

PMID- 10921853
TI  - Production of a glucoglucuronan by a rhizobia strain infecting alfalfa. Structure
      of the repeating unit.
AB  - The Rhizobium sp. T1 strain. which induces nodule formation on alfalfa and clover
      roots, produces, during growth, an extracellular polysaccharide composed of D
      glucose and D-glucuronic acid noted glucoglucuronan. During the bacterial growth,
      the pH of the medium decreases slightly. The control of pH in the growth medium
      slightly reduces the glucoglucuronan production. Under the conditions tested in
      the present work, the weight-average molecular weight of the polymers produced
      with or without pH control are similar: Mw approximately 2 x 10(6); the repeating
      unit determined by chemical and NMR analyses corresponds to the disaccharide: -->
      3)-beta-D-GlcpA-(1-->4)-beta-D-Glcp-(1 -->.

PMID- 10921854
TI  - Interactions and compatibility of ribuloso-1,5-bisphosphate carboxylase/oxygenase
      from alfalfa with pectin in aqueous medium.
AB  - HPLC, dynamic light scattering, CD- and fluorescent spectroscopy, and phase
      analysis methods are used to study the effect of Coulomb and non-Coulomb
      interactions between alfalfa rubisco and pectin on their thermodynamic
      compatibility. In the acid region of pH, water insoluble interpolymer complexes
      stabilized by both the Coulomb and non-Coulomb bonds are formed. In the neutral
      and alkaline regions, the complexes soluble in water are formed via non-Coulomb
      bonds, due to both the hydrophobic interaction involving the ester groups of
      pectin and the hydrogen bonding between dissimilar molecules. The compatibility
      of these biopolymers is sensitive to the esterification degree of pectin. With
      the latter increasing, compatability increases at neutral pH, but decreases
      considerably in the acidic region.

PMID- 10921855
TI  - Partial specific volume of hyaluronic acid in different media and conditions.
AB  - Density measurements of hyaluronic acid in different media and conditions have
      been made in order to determine the partial specific volumes, v0(2). We have
      studied the effects of temperature, type of cation, cation concentration, pH and
      solvent polarity on v0(2).

PMID- 10921857
TI  - First- and second-approximation calculations in the relaxation function of high
      sugar/polysaccharide systems.
AB  - The distribution function of Maxwellian relaxation times (phi) was derived from
      the small- deformation dynamic properties of high-sugar/agarose, /deacylated
      gellan and /high-methoxy pectin mixtures. First-approximation calculations of phi
      employed the time derivative of the experimentally measured storage and viscous
      moduli, with the two traces converging at the theoretically predicted slope of -
      0.5. Second-approximation calculations were based on phi, as derived by the first
      approximation, being a simple power function of relaxation times (tau(-m)). The
      slope m was measured at various points and used to derive correction factors for
      shifting the relaxation function to the second approximation. Thus, values of phi
      calculated from G' and G" were brought into satisfactory agreement, particularly
      in the recorded portion of the glass transition region. Once the function phi is
      accurately determined, it can be readily used for calculations of other
      viscoelastic properties.

PMID- 10921856
TI  - Binding of a fluorescent dansylcadaverine-substance P analogue to negatively
      charged phospholipid membranes.
AB  - We have investigated the binding of a new dansylcadaverine derivative of
      substance P (DNC-SP) with negatively charged small unilamellar vesicles composed
      of a mixture of phosphatidylcholine (PC) and either phosphatidylglycerol (PG) or
      phosphatidylserine (PS) using fluorescence spectroscopic techniques. The changes
      in fluorescence properties were used to obtain association isotherms at variable
      membrane negative charges and at different ionic strengths. The experimental
      association isotherms were analyzed using two binding approaches: (i) the
      Langmuir adsorption isotherm and the partition equilibrium model, that neglect
      the activity coefficients; and (ii) the partition equilibrium model combined with
      the Gouy-Chapman formalism that considers electrostatic effects. A consistent
      quantitative analysis of each DNC-SP binding curve at different lipid composition
      was achieved by means of the Gouy-Chapman approach using a peptide effective
      interfacial charge (v) value of (0.95 +/- 0.02), which is lower than the physical
      charge of the peptide. For PC/PG membranes, the partition equilibrium constant
      were 7.8 x 10(3) M(-1) (9/1, mol/mol) and 6.9 x 10(3) M(-1) (7/3, mol/mol),
      whereas for PC/PS membranes an average value of 6.8 x 10(3) M(-1) was estimated.
      These partition equilibrium constants were similar to those obtained for the
      interaction of DNC-SP with neutral PC membranes (4.9 x 10(3) M(-1)), as
      theoretically expected. We demonstrate that the v parameter is a determinant
      factor to obtain a unique value of the binding constant independently of the
      surface charge density of the vesicles. Also, the potential of fluorescent
      dansylated SP analogue in studies involving interactions with cell membranes is
      discussed.

PMID- 10921858
TI  - Deep-freezing of potato starch.
AB  - Samples of oven-dried, air-dried, and moisturised potato starch (5, 13, and 24%
      w/w moisture content, respectively) were frozen in liquid nitrogen. Samples after
      thawing were studied by means of cross-polarised light beam microscope (CLBM),
      Fourier Transformation Infrared Spectroscope (FT-IR), powder X-ray
      diffractometer, and non-contact Atomic Force Microscope (nc-AFM). Rapid deep
      freezing followed by thawing produced changes on the granule surface. They were
      accompanied by internal alteration manifested by FT-IR spectra and powder X-ray
      diffractograms. The results depended on the water content in the sample. Deep
      freezing of moistened starch resulted in increased crystallinity of granules. It
      had minor effect on the granule aqueous solubility and characteristics of
      gelation.

PMID- 10921866
TI  - EMBO workshop report. An eclipse over the cell nucleus functional organization of
      the cell nucleus Prague, August 9-12, 1999.
AB  - The EMBO workshop 'Functional Organization of the Cell Nucleus' held in Prague at
      the Hotel of the Postgraduate School of Medicine was attended by 110 participants
      (49 invited speakers and 61 selected participants) from 22 countries. Such a full
      range of topics devoted to the cell biology of the nucleus has not been discussed
      previously in such an intimate meeting in Europe. The workshop not only offered
      an opportunity for junior scientists to benefit from having an international
      meeting within Europe and a chance to discuss their work with internationally
      recognized experts, but it also offered a unique opportunity for interactions
      among the more established investigators. The fruits of a number of presentations
      are gathered together in a Special Issue of the Journal of Structural Biology
      which appeared in spring 2000. Last but not least, it is worth mentioning that
      while stepping through a packed scientific program, the participants did find the
      time to observe the solar eclipse just before the lunch break of August 11.

PMID- 10921867
TI  - Crystal structures of the metal-dependent 2-dehydro-3-deoxy-galactarate aldolase
      suggest a novel reaction mechanism.
AB  - Carbon-carbon bond formation is an essential reaction in organic chemistry and
      the use of aldolase enzymes for the stereochemical control of such reactions is
      an attractive alternative to conventional chemical methods. Here we describe the
      crystal structures of a novel class II enzyme, 2-dehydro-3-deoxy-galactarate
      (DDG) aldolase from Escherichia coli, in the presence and absence of substrate.
      The crystal structure was determined by locating only four Se sites to obtain
      phases for 506 protein residues. The protomer displays a modified (alpha/beta)(8)
      barrel fold, in which the eighth alpha-helix points away from the beta-barrel
      instead of packing against it. Analysis of the DDG aldolase crystal structures
      suggests a novel aldolase mechanism in which a phosphate anion accepts the proton
      from the methyl group of pyruvate.

PMID- 10921868
TI  - Crystal structure of a repair enzyme of oxidatively damaged DNA, MutM (Fpg), from
      an extreme thermophile, Thermus thermophilus HB8.
AB  - The MutM [formamidopyrimidine DNA glycosylase (Fpg)] protein is a trifunctional
      DNA base excision repair enzyme that removes a wide range of oxidatively damaged
      bases (N-glycosylase activity) and cleaves both the 3'- and 5'-phosphodiester
      bonds of the resulting apurinic/apyrimidinic site (AP lyase activity). The
      crystal structure of MutM from an extreme thermophile, Thermus thermophilus HB8,
      was determined at 1.9 A resolution with multiwavelength anomalous diffraction
      phasing using the intrinsic Zn(2+) ion of the zinc finger. MutM is composed of
      two distinct and novel domains connected by a flexible hinge. There is a large,
      electrostatically positive cleft lined by highly conserved residues between the
      domains. On the basis of the three-dimensional structure and taking account of
      previous biochemical experiments, we propose a DNA-binding mode and reaction
      mechanism for MutM. The locations of the putative catalytic residues and the two
      DNA-binding motifs (the zinc finger and the helix-two-turns-helix motifs) suggest
      that the oxidized base is flipped out from double-stranded DNA in the binding
      mode and excised by a catalytic mechanism similar to that of bifunctional base
      excision repair enzymes.

PMID- 10921869
TI  - Macromolecular crowding perturbs protein refolding kinetics: implications for
      folding inside the cell.
AB  - We have studied the effects of macromolecular crowding on protein folding
      kinetics by studying the oxidative refolding of hen lysozyme in the absence and
      presence of high concentrations of bovine serum albumin and Ficoll 70. The
      heterogeneity characteristic of the lysozyme refolding process is preserved under
      crowded conditions. This, together with the observation that the refolding
      intermediates that accumulate to significant levels are very similar in the
      absence and presence of Ficoll, suggests that crowding does not alter
      substantially the energetics of the protein folding reaction. However, the
      presence of high concentrations of macromolecules results in the acceleration of
      the fast track of the refolding process whereas the slow track is substantially
      retarded. The results can be explained by preferential excluded volume
      stabilization of compact states relative to more unfolded states, and suggest
      that, relative to dilute solutions, the rates of many protein folding processes
      are likely to be altered under conditions that more closely resemble the
      intracellular environment.

PMID- 10921870
TI  - Supramolecular structure of the Shigella type III secretion machinery: the needle
      part is changeable in length and essential for delivery of effectors.
AB  - We investigated the supramolecular structure of the SHIGELLA: type III secretion
      machinery including its major components. Our results indicated that the
      machinery was composed of needle and basal parts with respective lengths of 45.4
      +/- 3.3 and 31.6 +/- 0.3 nm, and contained MxiD, MxiG, MxiJ and MxiH. spa47,
      encoding a putative F(1)-type ATPase, was required for the secretion of effector
      proteins via the type III system and was involved in the formation of the needle.
      The spa47 mutant produced a defective, needle-less type III structure, which
      contained MxiD, MxiG and MxiJ but not MxiH. The mxiH mutant produced a defective
      type III structure lacking the needle and failed to secrete effector proteins.
      Upon overexpression of MxiH in the mxiH mutant, the bacteria produced type III
      structures with protruding dramatically long needles, and showed a remarkable
      increase in invasiveness. Our results suggest that MxiH is the major needle
      component of the type III machinery and is essential for delivery of the effector
      proteins, and that the level of MxiH affects the length of the needle.

PMID- 10921872
TI  - CD147 is tightly associated with lactate transporters MCT1 and MCT4 and
      facilitates their cell surface expression.
AB  - CD147 is a broadly expressed plasma membrane glycoprotein containing two
      immunoglobulin-like domains and a single charge-containing transmembrane domain.
      Here we use co-immunoprecipitation and chemical cross-linking to demonstrate that
      CD147 specifically interacts with MCT1 and MCT4, two members of the proton-linked
      monocarboxylate (lactate) transporter family that play a fundamental role in
      metabolism, but not with MCT2. Studies with a CD2-CD147 chimera implicate the
      transmembrane and cytoplasmic domains of CD147 in this interaction. In heart
      cells, CD147 and MCT1 co-localize, concentrating at the t-tubular and
      intercalated disk regions. In mammalian cell lines, expression is uniform but
      cross-linking with anti-CD147 antibodies caused MCT1, MCT4 and CD147, but not
      GLUT1 or MCT2, to redistribute together into 'caps'. In MCT-transfected cells,
      expressed protein accumulated in a perinuclear compartment, whereas co
      transfection with CD147 enabled expression of active MCT1 or MCT4, but not MCT2,
      in the plasma membrane. We conclude that CD147 facilitates proper expression of
      MCT1 and MCT4 at the cell surface, where they remain tightly bound to each other.
      This association may also be important in determining their activity and
      location.

PMID- 10921871
TI  - Roles of multimerization and membrane association in the proteolytic functions of
      FtsH (HflB).
AB  - FtsH (HflB) is an Escherichia coli ATP-dependent protease that degrades some
      integral membrane and cytoplasmic proteins. While anchored to the cytoplasmic
      membrane by the two transmembrane (TM) segments near the N-terminus, it has a
      large cytoplasmic domain. The N-terminal region also has a role in homo
      oligomerization of this protein. To study the significance of the membrane
      integration and oligomer formation, we constructed FtsH derivatives in which the
      N-terminal region had been deleted or replaced with either the leucine zipper
      sequence from Saccharomyces cerevisiae GCN4 protein or TM regions from other
      membrane proteins. The cytoplasmic domain, which was monomeric and virtually
      inactive, was converted, by the attachment of the leucine zipper, to an oligomer
      with proteolytic function against a soluble, but not a membrane-bound substrate.
      In contrast, chimeric TM-FtsH proteins were active against both substrate
      classes. We suggest that the cytoplasmic domain has intrinsic but weak self
      interaction ability, which becomes effective with the aid of the leucine zipper
      or membrane tethering, and that membrane association is essential for FtsH to
      degrade integral membrane proteins.

PMID- 10921873
TI  - COP I domains required for coatomer integrity, and novel interactions with ARF
      and ARF-GAP.
AB  - We performed a systematic mapping of interaction domains on COP I subunits to
      gain novel insights into the architecture of coatomer. Using the two-hybrid
      system, we characterize the domain structure of the alpha-, beta'-, epsilon-COP
      and beta-, gamma-, delta-, zeta-COP coatomer subcomplexes and identify links
      between them that contribute to coatomer integrity. Our results demonstrate that
      the domain organization of the beta-, gamma-, delta-, zeta-COP subcomplex and AP
      adaptor complexes is related. Through in vivo analysis of alpha-COP truncation
      mutants, we characterize distinct functional domains on alpha-COP. Its N-terminal
      WD40 domain is dispensable for yeast cell viability and overall coatomer
      function, but is required for KKXX-dependent trafficking. The last approximately
      170 amino acids of alpha-COP are also non-essential for cell viability, but
      required for epsilon-COP incorporation into coatomer and maintainance of normal
      epsilon-COP levels. Further, we demonstrate novel direct interactions of coatomer
      subunits with regulatory proteins: beta'- and gamma-COP interact with the ARF-GTP
      activating protein (GAP) Glo3p, but not Gcs1p, and beta- and epsilon-COP interact
      with ARF-GTP. Glo3p also interacts with intact coatomer in vitro.

PMID- 10921874
TI  - Incorporation of the nuclear pore basket protein nup153 into nuclear pore
      structures is dependent upon lamina assembly: evidence from cell-free extracts of
      Xenopus eggs.
AB  - In cell-free extracts of Xenopus eggs that support the assembly of replication
      competent nuclei, we found that lamin B(3) specifically associates with four
      polypeptides (termed SLAPs, soluble lamin associated proteins). Here, one SLAP is
      identified as the nuclear pore complex protein Nup153, one member of the F/GXFG
      motif-containing nucleoporins. In vitro translated Nup153 and lamin B(3) co
      immunoprecipitate, and lamin B(3) interacts specifically with the C-terminal
      domain of Nup153. During nuclear envelope assembly, other F/GXFG-containing
      nucleoporins are incorporated into the nuclear envelope preceding lamina
      assembly. Incorporation of Nup153 occurs at the same time as lamina assembly.
      When lamina assembly is prevented using the dominant-negative mutant XlaminB
      delta 2+, Nup153 does not appear at the nuclear envelope, while other F/GXFG
      containing nucleoporins and Nup93 are recruited normally. When the lamina of pre
      assembled nuclei is disrupted using the same dominant-negative mutant, the
      distribution of other nucleoporins is unaffected. However, Nup153 recruitment at
      the nuclear envelope is lost. Our results indicate that both the recruitment and
      maintenance of Nup153 at the pore are dependent upon the integrity of the lamina.

PMID- 10921875
TI  - Vaccinia virus infection disrupts microtubule organization and centrosome
      function.
AB  - We examined the role of the microtubule cytoskeleton during vaccinia virus
      infection. We found that newly assembled virus particles accumulate in the
      vicinity of the microtubule-organizing centre in a microtubule- and dynein
      dynactin complex-dependent fashion. Microtubules are required for efficient
      intracellular mature virus (IMV) formation and are essential for intracellular
      enveloped virus (IEV) assembly. As infection proceeds, the microtubule
      cytoskeleton becomes dramatically reorganized in a fashion reminiscent of
      overexpression of microtubule-associated proteins (MAPs). Consistent with this,
      we report that the vaccinia proteins A10L and L4R have MAP-like properties and
      mediate direct binding of viral cores to microtubules in vitro. In addition,
      vaccinia infection also results in severe reduction of proteins at the centrosome
      and loss of centrosomal microtubule nucleation efficiency. This represents the
      first example of viral-induced disruption of centrosome function. Further studies
      with vaccinia will provide insights into the role of microtubules during viral
      pathogenesis and regulation of centrosome function.

PMID- 10921876
TI  - APC(ste9/srw1) promotes degradation of mitotic cyclins in G(1) and is inhibited
      by cdc2 phosphorylation.
AB  - Fission yeast ste9/srw1 is a WD-repeat protein highly homologous to budding yeast
      Hct1/Cdh1 and Drosophila Fizzy-related that are involved in activating APC/C
      (anaphase-promoting complex/cyclosome). We show that APC(ste9/srw1) specifically
      promotes the degradation of mitotic cyclins cdc13 and cig1 but not the S-phase
      cyclin cig2. APC(ste9/srw1) is not necessary for the proteolysis of cdc13 and
      cig1 that occurs at the metaphase-anaphase transition but it is absolutely
      required for their degradation in G(1). Therefore, we propose that the main role
      of APC(ste9/srw1) is to promote degradation of mitotic cyclins when cells need to
      delay or arrest the cell cycle in G(1). We also show that ste9/srw1 is negatively
      regulated by cdc2-dependent protein phosphorylation. In G(1), when cdc2-cyclin
      kinase activity is low, unphosphorylated ste9/srw1 interacts with APC/C. In the
      rest of the cell cycle, phosphorylation of ste9/srw1 by cdc2-cyclin complexes
      both triggers proteolysis of ste9/srw1 and causes its dissociation from the
      APC/C. This mechanism provides a molecular switch to prevent inactivation of cdc2
      in G(2) and early mitosis and to allow its inactivation in G(1).

PMID- 10921877
TI  - Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr
      interferes with cell cycle signaling cascades by interacting with the B subunit
      of serine/threonine protein phosphatase 2A.
AB  - The Vpr protein of primate lentiviruses arrests cell cycling at the G(2)/M phase
      through an inactivation of cyclin B-p34(cdc2) and its upstream regulator cdc25.
      We provide here biochemical and functional evidence demonstrating that human
      immunodeficiency virus type 1 (HIV-1) Vpr mediates G(2) arrest by forming a
      complex with protein phosphatase 2A (PP2A), an upstream regulator of cdc25. Vpr
      associates with PP2A through a specific interaction with the B55 regulatory
      subunit. This interaction is necessary but not sufficient for G(2) arrest.
      Interestingly, we found that Vpr association with B55-containing PP2A targets the
      enzymatic complex to the nucleus and, importantly, enhances the recruitment and
      dephosphorylation of the cdc25 substrate. Our data suggest that Vpr mediates G(2)
      arrest by enhancing the nuclear import of PP2A and by positively modulating its
      catalytic activity towards active phosphorylated nuclear cdc25.

PMID- 10921878
TI  - Fission yeast Fizzy-related protein srw1p is a G(1)-specific promoter of mitotic
      cyclin B degradation.
AB  - Downregulation of cyclin-dependent kinase (Cdk)-mitotic cyclin complexes is
      important during cell cycle progression and in G(1) arrested cells undergoing
      differentiation. srw1p, a member of the Fizzy-related protein family in fission
      yeast, is required for the degradation of cdc13p mitotic cyclin B during G(1)
      arrest. Here we show that srw1p is not required for the degradation of cdc13p
      during mitotic exit demonstrating that there are two systems operative at
      different stages of the cell cycle for cdc13p degradation, and that srw1p is
      phosphorylated by Cdk-cdc13p only becoming dephosphorylated during G(1) arrest.
      We propose that this phosphorylation targets srw1p for proteolysis and inhibits
      its activity to promote cdc13p turnover.

PMID- 10921879
TI  - Mammalian LIN-7 PDZ proteins associate with beta-catenin at the cell-cell
      junctions of epithelia and neurons.
AB  - The heterotrimeric PDZ complex containing LIN-2, LIN-7 and LIN-10 is known to be
      involved in the organization of epithelial and neuronal junctions in
      Caenorhabditis elegans and mammals. We report here that mammalian LIN-7 PDZ
      proteins form a complex with cadherin and beta-catenin in epithelia and neurons.
      The association of LIN-7 with cadherin and beta-catenin is Ca(2+) dependent and
      is mediated by the direct binding of LIN-7 to the C-terminal PDZ target sequence
      of beta-catenin, as demonstrated by means of co-immunoprecipitation experiments
      and in vitro binding assays with the recombinant glutathione S-transferase:LIN
      7A. The presence of beta-catenin at the junction is required in order to relocate
      LIN-7 from the cytosol to cadherin-mediated adhesions, thus indicating that LIN-7
      junctional recruitment is beta-catenin dependent and that one functional role of
      the binding is to localize LIN-7. Moreover, when LIN-7 is present at the beta
      catenin-containing junctions, it determines the accumulation of binding partners,
      thus suggesting the mechanism by which beta-catenin mediates the organization of
      the junctional domain.

PMID- 10921880
TI  - Skin and hair follicle integrity is crucially dependent on beta 1 integrin
      expression on keratinocytes.
AB  - beta 1 integrins are ubiquitously expressed receptors that mediate cell-cell and
      cell-extracellular matrix interactions. To analyze the function of beta1 integrin
      in skin we generated mice with a keratinocyte-restricted deletion of the beta 1
      integrin gene using the cre-loxP system. Mutant mice developed severe hair loss
      due to a reduced proliferation of hair matrix cells and severe hair follicle
      abnormalities. Eventually, the malformed hair follicles were removed by
      infiltrating macrophages. The epidermis of the back skin became hyperthickened,
      the basal keratinocytes showed reduced expression of alpha 6 beta 4 integrin, and
      the number of hemidesmosomes decreased. Basement membrane components were
      atypically deposited and, at least in the case of laminin-5, improperly
      processed, leading to disruption of the basement membrane and blister formation
      at the dermal-epidermal junction. In contrast, the integrity of the basement
      membrane surrounding the beta 1-deficient hair follicle was not affected.
      Finally, the dermis became fibrotic. These results demonstrate an important role
      of beta 1 integrins in hair follicle morphogenesis, in the processing of basement
      membrane components, in the maintenance of some, but not all basement membranes,
      in keratinocyte differentiation and proliferation, and in the formation and/or
      maintenance of hemidesmosomes.

PMID- 10921881
TI  - Direct interaction of resistance gene and avirulence gene products confers rice
      blast resistance.
AB  - Rice expressing the Pi-ta gene is resistant to strains of the rice blast fungus,
      Magnaporthe grisea, expressing AVR-Pita in a gene-for-gene relationship. Pi-ta
      encodes a putative cytoplasmic receptor with a centrally localized nucleotide
      binding site and leucine-rich domain (LRD) at the C-terminus. AVR-Pita is
      predicted to encode a metalloprotease with an N-terminal secretory signal and pro
      protein sequences. AVR-Pita(176) lacks the secretory and pro-protein sequences.
      We report here that transient expression of AVR-Pita(176) inside plant cells
      results in a Pi-ta-dependent resistance response. AVR-Pita(176) protein is shown
      to bind specifically to the LRD of the Pi-ta protein, both in the yeast two
      hybrid system and in an in vitro binding assay. Single amino acid substitutions
      in the Pi-ta LRD or in the AVR-Pita(176) protease motif that result in loss of
      resistance in the plant also disrupt the physical interaction, both in yeast and
      in vitro. These data suggest that the AVR-Pita(176) protein binds directly to the
      Pi-ta LRD region inside the plant cell to initiate a Pi-ta-mediated defense
      response.

PMID- 10921882
TI  - Negative regulation of PI 3-kinase by Ruk, a novel adaptor protein.
AB  - Class I(A) phosphatidylinositol 3-kinase (PI 3-kinase) is a key component of
      important intracellular signalling cascades. We have identified an adaptor
      protein, Ruk(l), which forms complexes with the PI 3-kinase holoenzyme in vitro
      and in vivo. This interaction involves the proline-rich region of Ruk and the SH3
      domain of the p85 alpha regulatory subunit of the class I(A) PI 3-kinase. In
      contrast to many other adaptor proteins that activate PI 3-kinase, interaction
      with Ruk(l) substantially inhibits the lipid kinase activity of the enzyme.
      Overexpression of Ruk(l) in cultured primary neurons induces apoptosis, an effect
      that could be reversed by co-expression of constitutively activated forms of the
      p110 alpha catalytic subunit of PI 3-kinase or its downstream effector PKB/Akt.
      Our data provide evidence for the existence of a negative regulator of the PI 3
      kinase signalling pathway that is essential for maintaining cellular homeostasis.
      Structural similarities between Ruk, CIN85 and CD2AP/CMS suggest that these
      proteins form a novel family of adaptor molecules that are involved in various
      intracellular signalling pathways.

PMID- 10921883
TI  - Ligand-independent signals from angiotensin II type 2 receptor induce apoptosis.
AB  - Conventional models of ligand-receptor regulation predict that agonists enhance
      the tone of signals generated by the receptor in the absence of ligand. Contrary
      to this paradigm, stimulation of the type 2 (AT(2)) receptor by angiotensin II
      (Ang II) is not required for induction of apoptosis but the level of receptor
      protein expression is critical. We compared Ang II-dependent and -independent
      AT(2) receptor signals involved in regulating apoptosis of cultured fibroblasts,
      epithelial cells and vascular smooth muscle cells. We found that induction of
      apoptosis-blocked by pharmacological inhibition of p38 mitogen-activated protein
      kinase and caspase 3-is a constitutive function of the AT(2) receptor.
      Biochemical and genetic studies suggest that the level of AT(2) receptor
      expression is critical for physiological ontogenesis and its expression is
      restricted postnatally, coinciding with cessation of developmental apoptosis. Re
      expression of the AT(2) receptor in remodeling tissues in the adult is linked to
      control of tissue growth and regeneration. Therefore, we propose that
      overexpression of the AT(2) receptor itself is a signal for apoptosis that does
      not require the renin-angiotensin system hormone Ang II.

PMID- 10921885
TI  - FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary
      inflammation, defines a new gene family.
AB  - Bronchoalveolar lavage fluid from mice with experimentally induced allergic
      pulmonary inflammation contains a novel 9.4 kDa cysteine-rich secreted protein,
      FIZZ1 (found in inflammatory zone). Murine (m) FIZZ1 is the founding member of a
      new gene family including two other murine genes expressed, respectively, in
      intestinal crypt epithelium and white adipose tissue, and two related human
      genes. In control mice, FIZZ1 mRNA and protein expression occur at low levels in
      a subset of bronchial epithelial cells and in non-neuronal cells adjacent to
      neurovascular bundles in the peribronchial stroma, and in the wall of the large
      and small bowel. During allergic pulmonary inflammation, mFIZZ1 expression
      markedly increases in hypertrophic, hyperplastic bronchial epithelium and appears
      in type II alveolar pneumocytes. In vitro, recombinant mFIZZ1 inhibits the nerve
      growth factor (NGF)-mediated survival of rat embryonic day 14 dorsal root
      ganglion (DRG) neurons and NGF-induced CGRP gene expression in adult rat DRG
      neurons. In vivo, FIZZ1 may modulate the function of neurons innervating the
      bronchial tree, thereby altering the local tissue response to allergic pulmonary
      inflammation.

PMID- 10921884
TI  - Hypomyelination and increased activity of voltage-gated K(+) channels in mice
      lacking protein tyrosine phosphatase epsilon.
AB  - Protein tyrosine phosphatase epsilon (PTP epsilon) is strongly expressed in the
      nervous system; however, little is known about its physiological role. We report
      that mice lacking PTP epsilon exhibit hypomyelination of sciatic nerve axons at
      an early post-natal age. This occurs together with increased activity of delayed-
      rectifier, voltage-gated potassium (Kv) channels and with hyperphosphorylation of
      Kv1.5 and Kv2.1 Kv channel alpha-subunits in sciatic nerve tissue and in primary
      Schwann cells. PTP epsilon markedly reduces Kv1.5 or Kv2.1 current amplitudes in
      Xenopus oocytes. Kv2.1 associates with a substrate-trapping mutant of PTP
      epsilon, and PTP epsilon profoundly reduces Src- or Fyn-stimulated Kv2.1 currents
      and tyrosine phosphorylation in transfected HEK 293 cells. In all, PTP epsilon
      antagonizes activation of Kv channels by tyrosine kinases in vivo, and affects
      Schwann cell function during a critical period of Schwann cell growth and
      myelination.

PMID- 10921886
TI  - The RET proto-oncogene induces apoptosis: a novel mechanism for Hirschsprung
      disease.
AB  - The RET (rearranged during transfection) proto-oncogene encodes a tyrosine kinase
      receptor involved in both multiple endocrine neoplasia type 2 (MEN 2), an
      inherited cancer syndrome, and Hirschsprung disease (HSCR), a developmental
      defect of enteric neurons. We report here that the expression of RET receptor
      induces apoptosis. This pro-apoptotic effect of RET is inhibited in the presence
      of its ligand glial cell line-derived neurotrophic factor (GDNF). Furthermore, we
      present evidence that RET induces apoptosis via its own cleavage by caspases, a
      phenomenon allowing the liberation/exposure of a pro-apoptotic domain of RET. In
      addition, we report that Hirschsprung-associated RET mutations impair GDNF
      control of RET pro-apoptotic activity. These results indicate that HSCR may
      result from apoptosis of RET-expressing enteric neuroblasts.

PMID- 10921887
TI  - A repressor sequence in the juxtamembrane domain of Flt-1 (VEGFR-1)
      constitutively inhibits vascular endothelial growth factor-dependent
      phosphatidylinositol 3'-kinase activation and endothelial cell migration.
AB  - Vascular endothelial growth factor (VEGF) has two highly homologous tyrosine
      kinase receptors: Flt-1 (VEGFR-1) and KDR (VEGFR-2). KDR is strongly
      phosphorylated on tyrosines and can transmit mitogenic and motogenic signals
      following VEGF binding, while Flt-1 is markedly less effective in mediating such
      functions. To dissect the regions that account for the differences between the
      two receptors, we generated a series of chimeric Flt-1-KDR molecules. We found
      that the juxtamembrane region of Flt-1 prevents key signaling functions. When the
      juxtamembrane region of Flt-1 is replaced by that of KDR, Flt-1 becomes competent
      to mediate endothelial cell migration and phosphatidylinositol 3'-kinase
      activation in response to VEGF. Further mutational analysis shows that a short
      divergent sequence is responsible for such repressor function. However, mutant
      Flt-1 receptors lacking this sequence do not transmit effective proliferative
      signals, suggesting that this receptor function is regulated separately. These
      results define a novel functional domain that serves to repress Flt-1 activity in
      endothelial cells.

PMID- 10921888
TI  - Targeting of N-CoR and histone deacetylase 3 by the oncoprotein v-erbA yields a
      chromatin infrastructure-dependent transcriptional repression pathway.
AB  - Transcriptional repression by nuclear hormone receptors is thought to result from
      a unison of targeting chromatin modification and disabling the basal
      transcriptional machinery. We used Xenopus oocytes to compare silencing effected
      by the thyroid hormone receptor (TR) and its mutated version, the oncoprotein v
      ErbA, on partly and fully chromatinized TR-responsive templates in vivo.
      Repression by v-ErbA was not as efficient as that mediated by TR, was
      significantly more sensitive to histone deacetylase (HDAC) inhibitor treatment
      and, unlike TR, v-ErbA required mature chromatin to effect repression. We find
      that both v-ErbA and TR can recruit the corepressor N-CoR, but, in contrast to
      existing models, show a concomitant enrichment for HDAC3 that occurs without an
      association with Sin3, HDAC1/RPD3, Mi-2 or HDAC5. We propose a requirement for
      chromatin infrastructure in N-CoR/HDAC3-effected repression and suggest that the
      inability of v-ErbA to silence on partly chromatinized templates may stem from
      its impaired capacity to interfere with basal transcriptional machinery function.
      In support of this notion, we find v-ErbA to be less competent than TR for
      binding to TFIIB in vitro and in vivo.

PMID- 10921889
TI  - Derepression of DNA damage-regulated genes requires yeast TAF(II)s.
AB  - The general transcription factor TFIID and its individual subunits (TAF(II)s)
      have been the focus of many studies, yet their functions in vivo are not well
      established. Here we characterize the requirement of yeast TAF(II)s for the
      derepression of the ribonucleotide reductase (RNR) genes. Promoter mapping
      studies revealed that the upstream repressing sequences, the damage-responsive
      elements (DREs), rendered these genes dependent upon TAF(II)s. DREs are the
      binding sites for the sequence-specific DNA binding-protein Crt1 that represses
      transcription by recruiting the Ssn6-Tup1 co-repressor complex to the promoter.
      We demonstrate that deletion of SSN6, TUP1 or CRT1 alleviated the TAF(II)
      dependence of the RNR genes, indicating that TAF(II) dependence requires the co
      repressor complex. Furthermore, we provide evidence that Crt1 specifies the
      TAF(II) dependence of these genes. Our studies show that TFIID interacts with the
      repression domain of Crt1, suggesting that the derepression mechanism involves an
      antagonism between TFIID and the co-repressor complex. Our results indicate that
      yeast TAF(II)s have other functions in addition to core promoter selectivity, and
      describe a novel activity: the derepression of promoters.

PMID- 10921890
TI  - Selective stimulation of translation of leaderless mRNA by initiation factor 2:
      evolutionary implications for translation.
AB  - Translation initiation in bacteria involves a stochastic binding mechanism in
      which the 30S ribosomal subunit first binds either to mRNA or to initiator tRNA,
      fMet-tRNA(f)(Met). Leaderless lambda cI mRNA did not form a binary complex with
      30S ribosomes, which argues against the view that ribosomal recruitment signals
      other than a 5'-terminal start codon are essential for translation initiation of
      these mRNAs. We show that, in Escherichia coli, translation initiation factor 2
      (IF2) selectively stimulates translation of lambda cI mRNA in vivo and in vitro.
      These experiments suggest that the start codon of leaderless mRNAs is recognized
      by a 30S-fMet-tRNA(f)(Met)-IF2 complex, an intermediate equivalent to that
      obligatorily formed during translation initiation in eukaryotes. We further show
      that leaderless lambda cI mRNA is faithfully translated in vitro in both
      archaebacterial and eukaryotic translation systems. This suggests that
      translation of leaderless mRNAs reflects a fundamental capability of the
      translational apparatus of all three domains of life and lends support to the
      hypothesis that the translation initiation pathway is universally conserved.

PMID- 10921891
TI  - How Stat1 mediates constitutive gene expression: a complex of unphosphorylated
      Stat1 and IRF1 supports transcription of the LMP2 gene.
AB  - Analysis of mRNA levels in cells that express or lack signal transducers and
      activators of transcription 1 (Stat1) reveals that Stat1 mediates the
      constitutive transcription of many genes. Expression of the low molecular mass
      polypeptide 2 (LMP2), which requires Stat1, has been studied in detail. The
      overlapping interferon consensus sequence 2/gamma-interferon-activated sequence
      (ICS-2/GAS) elements in the LMP2 promoter bind to interferon regulatory factor 1
      (IRF1) and Stat1 and are occupied constitutively in vivo. The point mutant of
      Stat1, Y701F, which does not form dimers involving SH2-phosphotyrosine
      interactions, binds to the GAS element and supports LMP2 expression.
      Unphosphorylated Stat1 binds to IRF1 directly and we conclude that this complex
      uses the ICS-2/GAS element to mediate constitutive LMP2 transcription in vivo.
      The promoter of the IRF1 gene, which also contains a GAS site but not an adjacent
      ICS-2 site, is not activated by Stat1 Y701F. The promoters of other genes whose
      constitutive expression requires Stat1 may also utilize complexes of
      unphosphorylated Stat1 with IRF1 or other transcription factors.

PMID- 10921892
TI  - Regulation of matrix attachment region-dependent, lymphocyte-restricted
      transcription through differential localization within promyelocytic leukemia
      nuclear bodies.
AB  - Bright (B cell regulator of IgH transcription) transactivates the immunoglobulin
      heavy chain (IgH) intronic enhancer, Emicro, by binding to matrix attachment
      regions (MARs), sites necessary for DNA attachment to the nuclear matrix. Here we
      report that Bright interacts with the ubiquitous autoantigen Sp100, a component
      of promyelocytic leukemia nuclear bodies (PML NBs), and with LYSp100B/Sp140, the
      lymphoid-restricted homolog of Sp100. Both in intact cells and in nuclear matrix
      preparations, the majority of Bright and Sp100 colocalize within PML NBs. In
      contrast, Bright colocalizes with only a small fraction of LYSp100B while
      inducing a redistribution of the majority of LYSp100B from its associated nuclear
      domains (LANDs) into nucleoplasm and cytoplasm. Sp100 represses the MAR-binding
      and transactivation activity of Bright. LYSp100B interacts more weakly with
      Bright but requires significantly higher levels than Sp100 to inhibit MAR
      binding. However, it strongly stimulates Bright transactivation through E mu. We
      suggest that Sp100 and LYSp100B interactions with Bright have different
      consequences for IgH transcription, potentially through differential association
      of E mu MARs with nuclear matrix- associated PML NBs and LANDs.

PMID- 10921893
TI  - Alternatively spliced hBRF variants function at different RNA polymerase III
      promoters.
AB  - In yeast, a single form of TFIIIB is required for transcription of all RNA
      polymerase III (pol III) genes. It consists of three subunits: the TATA box
      binding protein (TBP), a TFIIB-related factor, BRF, and B". Human TFIIIB is not
      as well defined and human pol III promoters differ in their requirements for this
      activity. A human homolog of yeast BRF was shown to be required for transcription
      at the gene-internal 5S and VA1 promoters. Whether or not it was also involved in
      transcription from the gene-external human U6 promoter was unclear. We have
      isolated cDNAs encoding alternatively spliced forms of human BRF that can complex
      with TBP. Using immunopurified complexes containing the cloned hBRFs, we show
      that while hBRF1 functions at the 5S, VA1, 7SL and EBER2 promoters, a different
      variant, hBRF2, is required at the human U6 promoter. Thus, pol III utilizes
      different TFIIIB complexes at structurally distinct promoters.

PMID- 10921894
TI  - Developmentally regulated, alternative splicing of the Rpn10 gene generates
      multiple forms of 26S proteasomes.
AB  - The 26S proteasome is a multisubunit protein- destroying machinery that degrades
      ubiquitin-tagged proteins. To date only a single species of Rpn10, which possibly
      functions as a multiubiquitin chain-binding subunit, has been identified in
      various organisms. Here we report that mouse Rpn10 mRNAs occur in at least five
      distinct forms, named Rpn10a to Rpn10e, and that they are generated from a single
      gene by developmentally regulated, alternative splicing. Rpn10a is ubiquitously
      expressed, whereas Rpn10e is expressed only in embryos, with the highest levels
      of expression in the brain. Both forms of Rpn10 are components of the 26S
      proteasome, with an apparently similar affinity for multiubiquitylated
      [(125)I]lysozyme in vitro. However, they exert markedly divergent effects on the
      destruction of B-type cyclin in Xenopus egg extracts. Thus, the 26S proteasome
      occurs in at least two functionally distinct forms: one containing a ubiquitously
      expressed Rpn10a and the other a newly identified, embryo-specific Rpn10e. While
      the former is thought to perform proteolysis constitutively in a wide variety of
      cells, the latter may play a specialized role in early embryonic development.

PMID- 10921895
TI  - TIA-1 is a translational silencer that selectively regulates the expression of
      TNF-alpha.
AB  - TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the
      3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To
      determine the functional significance of this interaction, we used homologous
      recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide
      (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express
      similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce
      significantly more TNF-alpha protein than wild-type controls. The half-life of
      TNF-alpha transcripts is similar in wild-type and TIA-1(-/-) macrophages,
      indicating that TIA-1 does not regulate transcript stability. Rather, the absence
      of TIA-1 significantly increases the proportion of TNF-alpha transcripts that
      associate with polysomes, suggesting that TIA-1 normally functions as a
      translational silencer. TIA-1 does not appear to regulate the production of
      interleukin 1 beta, granulocyte-macrophage colony-stimulating factor or
      interferon gamma, indicating that its effects are, at least partially, transcript
      specific. Mice lacking TIA-1 are hypersensitive to the toxic effects of LPS,
      indicating that this translational control pathway may regulate the organismal
      response to microbial stress.

PMID- 10921896
TI  - Elongation arrest is a physiologically important function of signal recognition
      particle.
AB  - Signal recognition particle (SRP) targets proteins for co-translational insertion
      through or into the endoplasmic reticulum membrane. Mammalian SRP slows nascent
      chain elongation by the ribosome during targeting in vitro. This 'elongation
      arrest' activity requires the SRP9/14 subunit of the particle and interactions of
      the C-terminus of SRP14. We have purified SRP from Saccharomyces cerevisiae and
      demonstrated that it too has elongation arrest activity. A yeast SRP containing
      Srp14p truncated at its C-terminus (delta C29) did not maintain elongation
      arrest, was substantially deficient in promoting translocation and interfered
      with targeting by wild-type SRP. In vivo, this mutation conferred a constitutive
      defect in the coupling of protein translation and translocation and temperature
      sensitive growth, but only a slight defect in protein translocation. In
      combination, these data indicate that the primary defect in SRP delta C29 is in
      elongation arrest, and that this is a physiologically important and conserved
      function of eukaryotic SRP.

PMID- 10921897
TI  - Precise binding of single-stranded DNA termini by human RAD52 protein.
AB  - The human RAD52 protein, which exhibits a heptameric ring structure, has been
      shown to bind resected double strand breaks (DSBs), consistent with an early role
      in meiotic recombination and DSB repair. In this work, we show that RAD52 binds
      single-stranded and tailed duplex DNA molecules via precise interactions with the
      terminal base. When probed with hydroxyl radicals, ssDNA-RAD52 complexes exhibit
      a four-nucleotide repeat hypersensitivity pattern. This unique pattern is due to
      the interaction of RAD52 with either a 5' or a 3' terminus of the ssDNA, is
      sequence independent and is phased precisely from the terminal nucleotide.
      Hypersensitivity is observed over approximately 36 nucleotides, consistent with
      the length of DNA that is protected by RAD52 in nuclease protection assays. We
      propose that RAD52 binds DNA breaks via specific interactions with the terminal
      base, leading to the formation of a precisely organized ssDNA-RAD52 complex in
      which the DNA lies on an exposed surface of the protein. This protein-DNA
      arrangement may facilitate the DNA-DNA interactions necessary for RAD52-mediated
      annealing of complementary DNA strands.

PMID- 10921898
TI  - Dynamic relocalization of phage phi 29 DNA during replication and the role of the
      viral protein p16.7.
AB  - We have examined the localization of DNA replication of the Bacillus subtilis
      phage phi 29 by immunofluorescence. To determine where phage replication was
      localized within infected cells, we examined the distribution of phage
      replication proteins and the sites of incorporation of nucleotide analogues into
      phage DNA. On initiation of replication, the phage DNA localized to a single
      focus within the cell, nearly always towards one end of the host cell nucleoid.
      At later stages of the infection cycle, phage replication was found to have
      redistributed to multiple sites around the periphery of the nucleoid, just under
      the cell membrane. Towards the end of the cycle, phage DNA was once again
      redistributed to become located within the bulk of the nucleoid. Efficient
      redistribution of replicating phage DNA from the initial replication site to
      various sites surrounding the nucleoid was found to be dependent on the phage
      protein p16.7.

PMID- 10921899
TI  - Wnt signaling and cancer.

PMID- 10921900
TI  - Doing the MATH: is the mouse a good model for fly development?

PMID- 10921901
TI  - Activin receptor patterning of foregut organogenesis.
AB  - Foregut development produces a characteristic sequence of gastrointestinal and
      respiratory organs, but the signaling pathways that ensure this developmental
      order remain largely unknown. Here, mutations of activin receptors ActRIIA and
      ActRIIB are shown to disrupt the development of posterior foregut-derived organs,
      including the stomach, pancreas, and spleen. Foregut expression of genes
      including Shh and Isl1 is shifted in mutant mice. The endocrine pancreas is
      particularly sensitive to the type and extent of receptor inactivation.
      ActRIIA(+/-)B(+/-) animals lack axial defects, but have hypoplastic pancreatic
      islets, hypoinsulinemia, and impaired glucose tolerance. Thus, activin receptor
      mediated signaling regulates axial patterning, cell differentiation, and function
      of foregut-derived organs.

PMID- 10921902
TI  - Sip2p and its partner snf1p kinase affect aging in S. cerevisiae.
AB  - For a number of organisms, the ability to withstand periods of nutrient
      deprivation correlates directly with lifespan. However, the underlying molecular
      mechanisms are poorly understood. We show that deletion of the N
      myristoylprotein, Sip2p, reduces resistance to nutrient deprivation and shortens
      lifespan in Saccharomyces cerevisiae. This reduced lifespan is due to accelerated
      aging, as defined by loss of silencing from telomeres and mating loci, nucleolar
      fragmentation, and accumulation of extrachromosomal rDNA. Genetic studies
      indicate that sip2Delta produces its effect on aging by increasing the activity
      of Snf1p, a serine/threonine kinase involved in regulating global cellular
      responses to glucose starvation. Biochemical analyses reveal that as yeast age,
      hexokinase activity increases as does cellular ATP and NAD(+) content. The change
      in glucose metabolism represents a new correlate of aging in yeast and occurs to
      a greater degree, and at earlier generational ages in sip2Delta cells. Sip2p and
      Snf1p provide new molecular links between the regulation of cellular energy
      utilization and aging.

PMID- 10921903
TI  - Inactivation of mouse Hus1 results in genomic instability and impaired responses
      to genotoxic stress.
AB  - The eukaryotic cell cycle is overseen by regulatory mechanisms, termed
      checkpoints, that respond to DNA damage, mitotic spindle defects, and errors in
      the ordering of cell cycle events. The DNA replication and DNA damage cell cycle
      checkpoints of the fission yeast Schizosaccharomyces pombe require the hus1(+)
      (hydroxyurea sensitive) gene. To determine the role of the mouse homolog of
      hus1(+) in murine development and cell cycle checkpoint function, we produced a
      targeted disruption of mouse Hus1. Inactivation of Hus1 results in mid
      gestational embryonic lethality due to widespread apoptosis and defective
      development of essential extra-embryonic tissues. DNA damage-inducible genes are
      up-regulated in Hus1-deficient embryos, and primary cells from Hus1-null embryos
      contain increased spontaneous chromosomal abnormalities, suggesting that loss of
      Hus1 leads to an accumulation of genome damage. Embryonic fibroblasts lacking
      Hus1 fail to proliferate in vitro, but inactivation of p21 allows for the
      continued growth of Hus1-deficient cells. Hus1(-/-)p21(-/-) cells display a
      unique profile of significantly heightened sensitivity to hydroxyurea, a DNA
      replication inhibitor, and ultraviolet light, but only slightly increased
      sensitivity to ionizing radiation. Taken together, these results indicate that
      mouse Hus1 functions in the maintenance of genomic stability and additionally
      identify an evolutionarily-conserved role for Hus1 in mediating cellular
      responses to genotoxins.

PMID- 10921904
TI  - p300-mediated acetylation facilitates the transfer of histone H2A-H2B dimers from
      nucleosomes to a histone chaperone.
AB  - We have used a purified recombinant chromatin assembly system, including ACF (Acf
      1 + ISWI) and NAP-1, to examine the role of histone acetylation in ATP-dependent
      chromatin remodeling. The binding of a transcriptional activator (Gal4-VP16) to
      chromatin assembled using this recombinant assembly system dramatically enhances
      the acetylation of nucleosomal core histones by the histone acetyltransferase
      p300. This effect requires both the presence of Gal4-binding sites in the
      template and the VP16-activation domain. Order-of-addition experiments indicate
      that prior activator-meditated, ATP-dependent chromatin remodeling by ACF is
      required for the acetylation of nucleosomal histones by p300. Thus, chromatin
      remodeling, which requires a transcriptional activator, ACF and ATP, is an early
      step in the transcriptional process that regulates subsequent core histone
      acetylation. Glycerol gradient sedimentation and immunoprecipitation assays
      demonstrate that the acetylation of histones by p300 facilitates the transfer of
      H2A-H2B from nucleosomes to NAP-1. The results from these biochemical experiments
      suggest that (1) transcriptional activators (e.g., Gal4-VP16) and chromatin
      remodeling complexes (e.g., ACF) induce chromatin remodeling in the absence of
      histone acetylation; (2) transcriptional activators recruit histone
      acetyltransferases (e.g., p300) to promoters after chromatin remodeling has
      occurred; and (3) histone acetylation is important for a step subsequent to
      chromatin remodeling and results in the transfer of histone H2A-H2B dimers from
      nucleosomes to a histone chaperone such as NAP-1. Our results indicate a precise
      role for histone acetylation, namely to alter the structure of nucleosomes (e.g.,
      facilitate the loss of H2A-H2B dimers) that have been remodeled previously by the
      action of ATP-dependent chromatin remodeling complexes. Thus, transcription from
      chromatin templates is ordered and sequential, with precise timing and roles for
      ATP-dependent chromatin remodeling, subsequent histone acetylation, and
      alterations in nucleosome structure.

PMID- 10921905
TI  - A transcriptional insulator at the imprinted H19/Igf2 locus.
AB  - Igf2 and H19 exhibit parent-of-origin-specific monoallelic expression. H19 is
      expressed from the maternal chromosome and Igf2 from the paternal. The two genes
      share enhancer elements and monoallelic expression of both genes is dependent on
      cis-acting sequences upstream of the H19 promoter. In this work we examine the
      mechanisms by which this region silences the maternal Igf2 allele and we
      demonstrate that deletion of this region can result in high levels of activation
      of both H19 and Igf2 from a single chromosome. Moreover, by inserting this cis
      element between a promoter and its enhancer at a heterologous position, we
      demonstrate that the sequences carry both insulator activity and the ability to
      be stably imprinted. We also characterize the insulator in vitro and show that it
      is neither enhancer nor promoter specific.

PMID- 10921906
TI  - Translational control of C/EBPalpha and C/EBPbeta isoform expression.
AB  - Transcription factors derived from CCAAT/enhancer binding protein (C/EBP)alpha
      and C/EBPbeta genes control differentiation and proliferation in a number of cell
      types. Various C/EBP isoforms arise from unique C/EBPbeta and C/EBPalpha mRNAs by
      differential initiation of translation. These isoforms retain different parts of
      the amino terminus and therefore display different functions in gene regulation
      and proliferation control. We show that PKR and mTOR signaling pathways control
      the ratio of C/EBP isoform expression through the eukaryotic translation
      initiation factors eIF-2alpha and eIF-4E, respectively. An evolutionary conserved
      upstream open reading frame in C/EBPalpha and C/EBPbeta mRNAs is a prerequisite
      for regulated initiation from the different translation initiation sites and
      integrates translation factor activity. Deregulated translational control leading
      to aberrant C/EBPalpha and C/EBPbeta isoform expression or ectopic expression of
      truncated isoforms disrupts terminal differentiation and induces a transformed
      phenotype in 3T3-L1 cells. Our results demonstrate that the translational
      controlled ratio of C/EBPalpha and C/EBPbeta isoform expression determines cell
      fate.

PMID- 10921907
TI  - A C. elegans patched gene, ptc-1, functions in germ-line cytokinesis.
AB  - Patched (Ptc), initially identified in Drosophila, defines a class of multipass
      membrane proteins that control cell fate and cell proliferation. Biochemical
      studies in vertebrates indicate that the membrane proteins Ptc and Smoothened
      (Smo) form a receptor complex that binds Hedgehog (Hh) morphogens. Smo transduces
      the Hh signal to downstream effectors. The Caenorhabditis elegans genome encodes
      two Ptc homologs and one related pseudogene but does not encode obvious Hh or Smo
      homologs. We have analyzed ptc-1 by RNAi and mutational deletion and find that it
      is an essential gene, although the absence of ptc-1 has no detectable effect on
      body patterning or proliferation. Therefore, the C. elegans ptc-1 gene is
      functional despite the lack of Hh and Smo homologs. We find that the activity and
      expression of ptc-1 is essentially confined to the germ line and its progenitors.
      ptc-1 null mutants are sterile with multinucleate germ cells arising from a
      probable cytokinesis defect. We have also identified a surprisingly large family
      of PTC-related proteins containing sterol-sensing domains, including homologs of
      Drosophila dispatched, in C. elegans and other phyla. These results suggest that
      the PTC superfamily has multiple functions in animal development.

PMID- 10921908
TI  - members only encodes a Drosophila nucleoporin required for rel protein import and
      immune response activation.
AB  - Many developmental and physiological responses rely on the selective
      translocation of transcriptional regulators in and out of the nucleus through the
      nuclear pores. Here we describe the Drosophila gene members only (mbo) encoding a
      nucleoporin homologous to the mammalian Nup88. The phenotypes of mbo mutants and
      mbo expression during development are cell specific, indicating that the nuclear
      import capacity of cells is differentially regulated. Using inducible assays for
      nucleocytoplasmic trafficking we show that mRNA export and classic NLS-mediated
      protein import are unaffected in mbo mutants. Instead, mbo is selectively
      required for the nuclear import of the yeast transcription factor GAL4 in a
      subset of the larval tissues. We have identified the first endogenous targets of
      the mbo nuclear import pathway in the Rel proteins Dorsal and Dif. In mbo mutants
      the upstream signaling events leading to the degradation of the IkappaB homolog
      Cactus are functional, but Dorsal and Dif remain cytoplasmic and the larval
      immune response is not activated in response to infection. Our results
      demonstrate that distinct nuclear import events require different nucleoporins in
      vivo and suggest a regulatory role for mbo in signal transduction.

PMID- 10921909
TI  - FIN219, an auxin-regulated gene, defines a link between phytochrome A and the
      downstream regulator COP1 in light control of Arabidopsis development.
AB  - Light signals perceived by photoreceptors are transduced to negatively regulate
      COP1, a key repressor of photomorphogenic development. To identify genes involved
      in light inactivation of COP1, a genetic screen was employed to identify
      extragenic modifier mutations of a temperature-sensitive cop1 allele. One
      suppressor mutation isolated also exhibited a far-red-specific long hypocotyl
      phenotype in a wild-type background. Further phenotypic analyses of this new
      mutation, named fin219, suggested that it defines a novel phytochrome A signaling
      component. Genetic analysis indicated that FIN219 interacts closely with another
      phytochrome A signaling component, FHY1. Molecular characterization of FIN219
      indicated that it encodes a cytoplasmic localized protein highly similar to the
      GH3 family of proteins and its expression is rapidly induced by auxin. In
      contrast to its loss-of-function mutant phenotype, overexpression of FIN219
      results in a far-red-specific hyperphotomorphogenic response. Our data suggest
      that FIN219 may define a critical link for phytochrome A-mediated far-red
      inactivation of COP1 and a possible cross-talk juncture between auxin regulation
      and phytochrome signaling.

PMID- 10921910
TI  - RecE/RecT and Redalpha/Redbeta initiate double-stranded break repair by
      specifically interacting with their respective partners.
AB  - The initial steps of double-stranded break (DSB) repair by homologous
      recombination mediated by the 5'-3' exonuclease/annealing protein pairs,
      RecE/RecT and Redalpha/Redbeta, were analyzed. Recombination was RecA-independent
      and required the expression of both components of an orthologous pair, even when
      the need for exonuclease activity was removed by use of preresected substrates.
      The required orthologous function correlated with a specific protein-protein
      interaction, and recombination was favored by overexpression of the annealing
      protein with respect to the exonuclease. The need for both components of an
      orthologous pair was observed regardless of whether recombination proceeded via a
      single-strand annealing or a putative strand invasion mechanism. The DSB repair
      reactions studied here are reminiscent of the RecBCD/RecA reaction and suggest a
      general mechanism that is likely to be relevant to other systems, including RAD52
      mediated recombination.

PMID- 10921911
TI  - Cytoplasmic dynein ATPase activity is regulated by dynactin-dependent
      phosphorylation.
AB  - Cytoplasmic dynein is a microtubule-associated motor that utilizes ATP hydrolysis
      to conduct minus-end directed transport of various organelles. Dynactin is a
      multisubunit complex that has been proposed to both link dynein with cargo and
      activate dynein motor function. The mechanisms by which dynactin regulates dynein
      activity are not clear. In this study, we examine the role of dynactin in
      regulating dynein ATPase activity. We show that dynein-microtubule binding and
      ATP-dependent release of dynein from microtubules are reduced in dynactin null
      mutants, Deltaro-3 (p150(Glued)) and Deltaro-4 (Arp1), relative to wild-type. The
      dynein-microtubule binding activity, but not the ATP-dependent release of dynein
      from microtubules, is restored by in vitro mixing of extracts from dynein and
      dynactin mutants. Dynein produced in a Deltaro-3 mutant has approximately 8-fold
      reduced ATPase activity relative to dynein isolated from wild-type. However,
      dynein ATPase activity from wild-type is not reduced when dynactin is separated
      from dynein, suggesting that dynein produced in a dynactin mutant is inactivated.
      Treatment of dynein isolated from the Deltaro-3 mutant with lambda protein
      phosphatase restores the ATPase activity to near wild-type levels. The reduced
      dynein ATPase activity observed in dynactin null mutants is mainly due to altered
      affinity for ATP. Radiolabeling experiments revealed that low molecular mass
      proteins, particularly 20- and 8-kDa proteins, that immunoprecipitate with dynein
      heavy chain are hyperphosphorylated in the dynactin mutant and dephosphorylated
      upon lambda protein phosphatase treatment. The results suggest that cytoplasmic
      dynein ATPase activity is regulated by dynactin-dependent phosphorylation of
      dynein light chains.

PMID- 10921912
TI  - Transcriptional activation of the human ucp1 gene in a rodent cell line.
      Synergism of retinoids, isoproterenol, and thiazolidinedione is mediated by a
      multipartite response element.
AB  - Uncoupling protein 1 (UCP1) is uniquely expressed in brown adipocytes and
      generates heat production by uncoupling respiration from ATP synthesis. The
      activatory effects of norepinephrine and retinoic acid (RA) on rodent ucp1 gene
      transcription have been well characterized. These effects are mediated by a 211
      base pair (bp) enhancer which is also sufficient to restrict expression to brown
      adipose tissue. The molecular mechanisms controlling the transcription of the
      human ucp1 gene are unknown. In order to study the transcriptional regulation of
      the human gene, we set up chloramphenicol acetyltransferase constructs containing
      the entire or deleted 5' regions upstream of the transcriptional start site of
      the gene. These constructs were transiently transfected in a mouse cell line. A
      350-bp hormone response region showing a significant homology with the rat ucp1
      enhancer and located between the BclI polymorphic site and an AatII site (bp 
      3820/-3470) was detected. This region was sufficient to mediate the stimulation
      by RA and by combined treatments (RA + isoproterenol (ISO), RA +
      thiazolidinedione (TZD), or RA + ISO + TZD). The highest stimulation, a 26-fold
      increase in basal activity, was obtained by RA + ISO + TZD treatment. In contrast
      to the rodent gene, under our conditions, the effect of ISO and/or TZD is
      dependent on RA stimulation. Analysis of 105 bp inside the 350-bp element by site
      directed mutagenesis and gel retardation experiments demonstrated that a
      multipartite response element mediates the drug stimulation. This region binds
      RARs and RXRs nuclear factors, CREB/ATF factors, and also PPARgamma despite the
      absence of a consensus peroxisome-proliferator response element. The activation
      of the human ucp1 gene transcription by certain hormones or drugs, and the
      identification of the cis-elements involved, will help to identify new compounds
      activating fat oxidation and energy expenditure in humans.

PMID- 10921913
TI  - Amlexanox reversibly inhibits cell migration and proliferation and induces the
      Src-dependent disassembly of actin stress fibers in vitro.
AB  - Amlexanox binds S100A13 and inhibits the release of fibroblast growth factor 1
      (FGF1). Because members of the S100 gene family are known to be involved with the
      function of the cytoskeleton, we examined the ability of amlexanox to modify the
      cytoskeleton and report that amlexanox induces a dramatic reduction in the
      presence of actin stress fibers and the appearance of a random, non-oriented
      distribution of focal adhesion sites. Correspondingly, amlexanox induces the
      complete and reversible non-apoptotic inhibition of cell migration and
      proliferation, and although amlexanox does not induce either the down-regulation
      of F-actin levels or the depolymerization of actin filaments, it does induce the
      tyrosine phosphorylation of cortactin, a Src substrate known to regulate actin
      bundling. In addition, a dominant negative form of Src is able to partially
      rescue cells from the effect of amlexanox on both the actin cytoskeleton and cell
      migration. In contrast, the inhibition of cell proliferation by amlexanox
      correlates with the inhibition of cyclin D1 expression without interference of
      the receptor tyrosine kinase/mitogen-activated protein kinase signaling pathway.
      Last, the ability of amlexanox to inhibit FGF1 release is reversible and
      correlates with the restoration of the actin cytoskeleton, suggesting a role for
      the actin cytoskeleton in the FGF1 release pathway.

PMID- 10921914
TI  - ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of
      TRAF6-TAK1 interaction.
AB  - Apoptosis signal-regulating kinase 1 (ASK1) is a member of the MAPKKK family in
      the JNK and p38 mitogen-activated protein kinase cascades and critically involved
      in stress- and cytokine-induced apoptosis. The transcription factor nuclear
      factor-kappaB (NF-kappaB) is a pivotal regulator of immune and inflammatory
      responses and exerts anti-apoptotic roles in various cells. Here we show that
      ASK1 directly interacts with transforming growth factor-beta-activated kinase 1
      (TAK1), another MAPKKK that has been identified as a signaling intermediate in
      the interleukin 1 (IL-1)-induced NF-kappaB pathway as well as the transforming
      growth factor-beta superfamily-induced JNK/p38 pathway. Overexpression of ASK1
      inhibits IL-1-, TRAF6-, or TAK1-induced, but not NF-kappaB-inducing kinase
      induced, NF-kappaB activation. ASK1 dissociates TAK1 but not NF-kappaB-inducing
      kinase from TRAF6. Moreover, IL-1-induced complex formation of endogenous TAK1
      and TRAF6 was blocked by ASK1 overexpression. It thus appears that the inhibition
      of NF-kappaB by ASK1 may result at least in part from the disruption of the
      TRAF6.TAK1 complex formation in the IL-1 signaling pathway. These results provide
      a new insight in the mode of action of MAPKKK family members; two distinct
      MAPKKKs in the same MAP kinase cascades directly interact and exert opposite
      effects in another signaling pathway, NF-kappaB.

PMID- 10921915
TI  - Agonist-modulated targeting of the EDG-1 receptor to plasmalemmal caveolae. eNOS
      activation by sphingosine 1-phosphate and the role of caveolin-1 in sphingolipid
      signal transduction.
AB  - Plasmalemmal caveolae are membrane microdomains that are specifically enriched in
      sphingolipids and contain a wide array of signaling proteins, including the
      endothelial isoform of nitric-oxide synthase (eNOS). EDG-1 is a G protein-coupled
      receptor for sphingosine 1-phosphate (S1P) that is expressed in endothelial cells
      and has been implicated in diverse vascular signal transduction pathways. We
      analyzed the subcellular distribution of EDG-1 in COS-7 cells transiently
      transfected with cDNA constructs encoding epitope-tagged EDG-1. Subcellular
      fractionation of cell lysates resolved by ultracentrifugation in discontinuous
      sucrose gradients revealed that approximately 55% of the EDG-1 protein was
      recovered in fractions enriched in caveolin-1, a resident protein of caveolae. Co
      immunoprecipitation experiments showed that EDG-1 could be specifically
      precipitated by antibodies directed against caveolin-1 and vice versa. The
      targeting of EDG-1 to caveolae-enriched fractions was markedly increased (from 51
      +/- 11% to 93 +/- 14%) by treatment of transfected cells with S1P (5 microm, 60
      min). In co-transfection experiments expressing EDG-1 and eNOS cDNAs in COS-7
      cells, we found that S1P treatment significantly and specifically increased
      nitric-oxide synthase activity, with an EC(50) of 30 nm S1P. Overexpression of
      transfected caveolin-1 cDNA together with EDG-1 and eNOS markedly diminished S1P
      mediated eNOS activation; caveolin overexpression also attenuated agonist-induced
      phosphorylation of EDG-1 receptor by >90%. These results suggest that the
      interaction of the EDG-1 receptor with caveolin may serve to inhibit signaling
      through the S1P pathway, even as the targeting of EDG-1 to caveolae facilitates
      the interactions of this receptor with ligands and effectors that are also
      targeted to caveolae. The agonist-modulated targeting of EDG-1 to caveolae and
      its dynamic inhibitory interactions with caveolin identify new points for
      regulation of sphingolipid-dependent signaling in the vascular wall.

PMID- 10921916
TI  - Specific isoforms of the resident endoplasmic reticulum protein glucosidase II
      associate with the CD45 protein-tyrosine phosphatase via a lectin-like
      interaction.
AB  - We have previously demonstrated that CD45 physically associates with the
      endoplasmic reticulum processing enzyme glucosidase II (GII). GII consists of the
      catalytic alpha-chain and an associated beta-chain. To gain insight into the
      basis of the association between CD45 and GII, we examined the biochemical
      requirements for the interaction. We show that the alpha-subunit is essential for
      the interaction. Interestingly, only a higher molecular weight form of GIIalpha
      is capable of associating with CD45 in a competitive situation where multiple
      GIIalpha isoforms are expressed. Further, transfection studies demonstrate that
      only isoforms containing the alternatively spliced sequence Box A1 are capable of
      binding CD45, although all isoforms are catalytically active. The interaction
      between CD45 and GII is dependent on the active site of GII, is mediated through
      the carbohydrate on CD45, and can be inhibited with mannose. Taken together,
      these results suggest that GIIalpha acts as a lectin and binds to CD45 in an exon
      dependent manner. This lectin activity of GII may be a novel mechanism for the
      regulation of CD45 biology and play a role in immune function, possibly by
      regulating CD45 glycosylation.

PMID- 10921917
TI  - Cell volume-dependent phosphorylation of proteins of the cortical cytoskeleton
      and cell-cell contact sites. The role of Fyn and FER kinases.
AB  - Cell volume affects diverse functions including cytoskeletal organization, but
      the underlying signaling pathways remained undefined. We have shown previously
      that shrinkage induces Fyn-dependent tyrosine phosphorylation of the cortical
      actin-binding protein, cortactin. Because FER kinase was implicated in the direct
      phosphorylation of cortactin, we investigated the osmotic responsiveness of FER
      and its relationship to Fyn and cortactin. Shrinkage increased FER activity and
      tyrosine phosphorylation. These effects were abolished by the Src family
      inhibitor PP2 and strongly mitigated in Fyn-deficient but not in Src-deficient
      cells. FER overexpression caused cortactin phosphorylation that was further
      enhanced by hypertonicity. Exchange of tyrosine residues 421, 466, and 482 for
      phenylalanine prevented cortactin phosphorylation by hypertonicity and strongly
      decreased it upon FER overexpression, suggesting that FER targets primarily the
      same osmo-sensitive tyrosines. Because constituents of the cell-cell contacts are
      substrates of Fyn and FER, we investigated the effect of shrinkage on the
      adherens junctions. Hypertonicity provoked Fyn-dependent tyrosine phosphorylation
      in beta-catenin, alpha-catenin, and p120(Cas) and caused the dissociation of beta
      catenin from the contacts. This process was delayed in Fyn-deficient or PP2
      treated cells. Thus, FER is a volume-sensitive kinase downstream from Fyn, and
      the Fyn/FER pathway may contribute to the cell size-dependent reorganization of
      the cytoskeleton and the cell-cell contacts.

PMID- 10921918
TI  - Molecular defects that cause loss of polysialic acid in the complementation group
      2A10.
AB  - Polysialic acid (PSA) is a dynamically regulated posttranslational modification
      of the neural cell adhesion molecule (NCAM), which modulates NCAM binding
      functions. PSA biosynthesis is catalyzed by two polysialyltransferases, ST8SiaII
      and ST8SiaIV. The catalytic mechanisms of these enzymes are unknown. In Chinese
      hamster ovary cells, ST8SiaIV is responsible for PSA expression. In the
      complementation group 2A10, the ST8SiaIV gene is disrupted. Investigating the
      molecular defects in this complementation group, seven clones with missense
      mutations in ST8SiaIV were found. Mutations cause replacement of amino acids that
      are highly conserved in alpha2,8-sialyltransferases. To verify the physiological
      relevance of identified mutations, identical amino acid substitutions were
      introduced into epitope-tagged variants of hamster ST8SiaIV and murine ST8SiaII
      and recombinant proteins were tested in vivo and in vitro. None of these
      constructs reconstituted PSA synthesis in 2A10 cells, although the proteins were
      expressed and with the exception of the cysteine variants ST8SiaIV-C356F and
      ST8SiaII-C371F correctly targeted to the Golgi apparatus. Interestingly, two
      mutations (ST8SiaIV-R277G and -M333V and the corresponding mutants ST8SiaII-R292G
      and -M348V) could be partially rescued if tested in vitro. Although these mutants
      were negative for autopolysialylation, partial reconstitution of both auto- and
      NCAM polysialylation was achieved in the presence of NCAM. The data presented in
      this study suggest a functional link between auto- and NCAM polysialylation.

PMID- 10921919
TI  - Quaternary structure of the lactose transport protein of Streptococcus
      thermophilus in the detergent-solubilized and membrane-reconstituted state.
AB  - The quaternary structure of LacS, the lactose transporter of Streptococcus
      thermophilus, has been determined for the detergent-solubilized and the membrane
      reconstituted state of the protein. The quaternary structure of the n-dodecyl
      beta-d-maltoside-solubilized state was studied using a combination of
      sedimentation velocity and equilibrium centrifugation analysis. From these
      measurements it followed that the detergent-solubilized LacS undergoes reversible
      self-association with a monomer to dimer mode of association. The association
      constants were 5.4 +/- 3.6 and 4.4 +/- 1.0 ml mg(-1) as determined from the
      velocity and equilibrium sedimentation measurements, respectively. The
      experiments did not indicate significant changes in the shape of the protein
      detergent complex or the amount of detergent bound in going from the monomeric to
      dimeric state of LacS. Importantly, a single Cys mutant of LacS is labeled by 2
      (4'-maleimidylanilino)naphthalene-6-sulfonic acid in a substrate-dependent
      manner, indicating that the detergent-solubilized protein exhibits ligand binding
      activity. The quaternary structure of membrane-reconstituted LacS was determined
      by freeze-fracture electron microscopy analysis. Recent developments in the
      analysis of freeze-fracture images (Eskandari, S. P., Wright, E. M., Freman, M.,
      Starace, D. M., and Zampighi, G. A. (1998) Proc. Natl. Acad. Sci. U. S. A. 95,
      11235-11240) allowed us to directly correlate the cross-sectional area of the
      transmembrane segment to a dimeric state of the functionally membrane
      reconstituted LacS protein. The cross-sectional area of the LacS protein was
      calibrated using the membrane-reconstituted transmembrane domain of the mannitol
      transporter enzyme II, an intramembrane particle for which the cross-sectional
      area was obtained from maps of two-dimensional crystals. The consequences of the
      determined quaternary structure for the transport function and regulation of LacS
      are discussed.

PMID- 10921921
TI  - Cadmium-inducible expression of the yeast GSH1 gene requires a functional sulfur
      amino acid regulatory network.
AB  - Glutathione (gamma-l-glutamyl-l-cysteinylglycine) is an important antioxidant
      molecule, helping to buffer the cell against free radicals and toxic
      electrophiles. Expression of the yeast GSH1 gene, encoding the first enzyme
      involved in glutathione biosynthesis, gamma-glutamylcysteine synthetase, is
      regulated by oxidants and the heavy metal cadmium at the level of transcription.
      We present evidence that the transcription factors involved in controlling the
      network of sulfur amino acid metabolism genes are also responsible for regulating
      GSH1 expression in response to cadmium. In particular the transcription factors
      Met-4, Met-31, and Met-32 are essential for cadmium-mediated regulation of gene
      expression, whereas the DNA-binding protein Cbf1 appears to play a negative role
      in controlling GSH1 expression.

PMID- 10921920
TI  - A novel beta-catenin-binding protein inhibits beta-catenin-dependent Tcf
      activation and axis formation.
AB  - beta-Catenin is efficiently phosphorylated by glycogen synthase kinase-3beta in
      the Axin complex in the cytoplasm, resulting in the down-regulation. In response
      to Wnt, beta-catenin is stabilized and translocated into the nucleus where it
      stimulates gene expression through Tcf/Lef. Here we report a novel protein,
      designated Duplin (for axis duplication inhibitor), which negatively regulates
      the function of beta-catenin in the nucleus. Duplin was located in the nucleus.
      Duplin bound directly to the Armadillo repeats of beta-catenin, thereby
      inhibiting the binding of Tcf to beta-catenin. It did not affect the stability of
      beta-catenin but inhibited Wnt- or beta-catenin-dependent Tcf activation.
      Furthermore, expression of Duplin in Xenopus embryos inhibited the axis formation
      and beta-catenin-dependent axis duplication, and prevented the beta-catenin's
      ability to rescue ventralizing phenotypes induced by ultraviolet light
      irradiation. Thus, Duplin is a nuclear protein that inhibits beta-catenin
      signaling.

PMID- 10921922
TI  - Intracellular signaling mechanisms leading to synergistic effects of endothelin-1
      and stem cell factor on proliferation of cultured human melanocytes. Cross-talk
      via trans-activation of the tyrosine kinase c-kit receptor.
AB  - We previously reported that activation of mitogen-activated protein kinase (MAPK)
      is involved in the mitogenic stimulation of normal human melanocytes (NHMC) by
      endothelin-1 (ET-1). In the present study, we determined signaling mechanisms
      upstream of MAPK activation that are involved in ET-1 stimulation and their
      synergism with stem cell factor (SCF). Pretreatment of cultured NHMC with ET(B)
      receptor antagonists, pertussis toxin, a specific phospholipase C inhibitor (),
      or a protein kinase C inhibitor (calphostine) blocked a transient tyrosine
      phosphorylation of MAPK induced by ET-1, whereas the addition of a calcium
      chelator (BAPTA) failed to inhibit that tyrosine phosphorylation of MAPK.
      Treatment with ET-1 and SCF together synergistically increased DNA synthesis,
      which was accompanied by synergism for MAPK phosphorylation. The time course of
      inositol 1,4,5-trisphosphate formation revealed that there is no difference in
      the level of inositol 1,4,5-trisphosphate stimulated by ET-1 + SCF or by ET-1
      alone. Evaluations of the serine phosphorylation of MEK and Raf-1 activity showed
      a synergistic effect in SCF + ET-1-treated NHMC. Stimulation with SCF + ET-1
      induced a more rapid and stronger tyrosyl phosphorylation of proteins
      corresponding to p52 and p66 Shc than did stimulation with SCF only, and this was
      accompanied by a stronger association of tyrosine-phosphorylated Shc with Grb2.
      Interestingly, a more rapid and marked tyrosine phosphorylation of c-kit was also
      detected in NHMC-treated with SCF + ET-1 than NHMC treated with SCF only. These
      data indicate that the synergistic cross-talk between SCF and ET-1 signaling is
      initiated through the pathway of tyrosine phosphorylation of c-kit, which results
      in the enhanced formation of the Shc-Grb(2) complex which leads in turn to the
      synergistic activation of the Ras/Raf-1/MEK/MAP kinase loop.

PMID- 10921923
TI  - Conjugation of Nedd8 to CUL1 enhances the ability of the ROC1-CUL1 complex to
      promote ubiquitin polymerization.
AB  - The SCF-ROC1 ubiquitin-protein isopeptide ligase (E3) ubiquitin ligase complex
      targets the ubiquitination and subsequent degradation of protein substrates
      required for the regulation of cell cycle progression and signal transduction
      pathways. We have previously shown that ROC1-CUL1 is a core subassembly within
      the SCF-ROC1 complex, capable of supporting the polymerization of ubiquitin. This
      report describes that the CUL1 subunit of the bacterially expressed, unmodified
      ROC1-CUL1 complex is conjugated with Nedd8 at Lys-720 by HeLa cell extracts or by
      a purified Nedd8 conjugation system (consisting of APP-BP1/Uba3, Ubc12, and
      Nedd8). This covalent linkage of Nedd8 to CUL1 is both necessary and sufficient
      to markedly enhance the ability of the ROC1-CUL1 complex to promote ubiquitin
      polymerization. A mutation of Lys-720 to arginine in CUL1 eliminates the Nedd8
      modification, abolishes the activation of the ROC1-CUL1 ubiquitin ligase complex,
      and significantly reduces the ability of SCF(HOS/beta)(-TRCP)-ROC1 to support the
      ubiquitination of phosphorylated IkappaBalpha. Thus, although regulation of the
      SCF-ROC1 action has been previously shown to preside at the level of recognition
      of a phosphorylated substrate, we demonstrate that Nedd8 is a novel regulator of
      the efficiency of polyubiquitin chain synthesis and, hence, promotes rapid
      turnover of protein substrates.

PMID- 10921924
TI  - Regulation of monovalent ion homeostasis and pH by the Ser-Thr protein
      phosphatase SIT4 in Saccharomyces cerevisiae.
AB  - A gene, SIT4, was identified as corresponding to a serine/threonine protein
      phosphatase and when overexpressed confers lithium tolerance in galactose medium
      to the budding yeast Saccharomyces cerevisiae. This gene has been previously
      identified as a regulator of the cell cycle and involved in nitrogen sensing. It
      is shown that the transcription levels of SIT4 are induced by low concentrations
      of Li(+) in a time-dependent manner. Na(+) and K(+) at high concentrations, but
      not sorbitol, also induce transcription. As a response to Na(+) or Li(+) stress,
      yeast cells lower the intracellular K(+) content. This effect is enhanced in
      cells overexpressing SIT4, which also increase (86)Rb efflux after the addition
      of Na(+) or Li(+) to the extracellular medium. Another feature of SIT4
      overexpressing cells is that they maintain a more alkaline pH of 6.64 compared
      with 6.17 in the wild type cells. It has been proposed that the main pathway of
      salt tolerance in yeast is mediated by a P-type ATPase, encoded by PMR2A/ENA1.
      However, our results show that in a sit4 strain, expression of ENA1 is still
      induced by monovalent cations, and overexpression of SIT4 does not alter the
      amount of ENA1 transcript. These results show that SIT4 acts in a parallel
      pathway not involving induction of transcription of ENA1 and suggest a novel
      function for SIT4 in response to salt stress.

PMID- 10921925
TI  - Effects of lipid interaction on the lysine microenvironments in apolipoprotein E.
AB  - Lysines in apolipoprotein (apo) E are key factors in the binding of apoE to the
      low density lipoprotein receptor, and high affinity binding requires that apoE be
      associated with lipid. To gain insight into this effect, we examined the
      microenvironments of the eight lysines in the 22-kDa fragment of apoE3 (residues
      1-191) in the lipid-free and lipid-associated states. As shown by (1)H,(13)C
      heteronuclear single quantum coherence nuclear magnetic resonance, lysine
      resonances in the lipid-free fragment were poorly resolved over a wide pH range,
      whereas in apoE3.dimyristoyl phosphatidylcholine (DMPC) discs, the lysine
      microenvironments and protein conformation were significantly altered. Sequence
      specific assignments of the lysine resonances in the spectrum of the lipidated 22
      kDa fragment were made. In the lipid-free protein, six lysines could be resolved,
      and all had pK(a) values above 10. In apoE3.DMPC complexes, however, all eight
      lysines were resolved, and the pK(a) values were 9.2-11.1. Lys-143 and Lys-146,
      both in the receptor binding region in helix 4, had unusually low pK(a) values of
      9.5 and 9.2, respectively, likely as a result of local increases in positive
      electrostatic potential with lipid association. Shift reagent experiments with
      potassium ferricyanide showed that Lys-143 and Lys-146 were much more accessible
      to the ferricyanide anion in the apoE3.DMPC complex than in the lipid-free state.
      The angle of the nonpolar face of helix 4 is smaller than the angles of helices
      1, 2, and 3, suggesting that helix 4 cannot penetrate as deeply into the DMPC
      acyl chains at the edge of the complex and that its polar face protrudes from the
      edge of the disc. This increased exposure and the greater positive electrostatic
      potential created by interaction with DMPC may explain why lipid association is
      required for high affinity binding of apoE to the low density lipoprotein
      receptor.

PMID- 10921926
TI  - The importance of the carboxyl-terminal domain of cardiac troponin C in Ca2+
      sensitive muscle regulation.
AB  - The interactions between troponin I and troponin C are central to the Ca(2+)
      regulated control of striated muscle. Using isothermal titration microcalorimetry
      we have studied the binding of human cardiac troponin C (cTnC) and its isolated
      domains to human cardiac troponin I (cTnI). We provide the first binding data for
      these proteins while they are free in solution and unmodified by reporter groups.
      Our data reveal that the C-terminal domain of cTnC is responsible for most of the
      free energy change upon cTnC.cTnI binding. Importantly, the interaction between
      cTnI and the C-terminal domain of cTnC is 8-fold stronger in the presence of
      Ca(2+) than in the presence of Mg(2+), suggesting that the C-terminal domain of
      cTnC may play a modulatory role in cardiac muscle regulation. Changes in the
      affinity of cTnI for cTnC and its isolated C-terminal domain in response to ionic
      strength support this finding, with both following similar trends. At
      physiological ionic strength the affinity of cTnC for cTnI changed very little in
      response to Ca(2+), although the thermodynamic data show a clear distinction
      between binding in the presence of Ca(2+) and in the presence of Mg(2+).

PMID- 10921928
TI  - The Pit-1beta domain dictates active repression and alteration of histone
      acetylation of the proximal prolactin promoter.
AB  - A critical problem in current molecular biology is to gain a detailed
      understanding of the molecular mechanisms by which related transcription factor
      isoforms with identical DNA sequence specificity mediate distinct transcription
      responses. Pit-1 and Pit-1beta constitute such a pair of transcription factor
      isoforms. Pit-1 enhances the Ras signaling pathway to the prolactin promoter, and
      Pit-1beta represses basal prolactin promoter activity as well as Ras signaling to
      the prolactin promoter in pituitary cells. We have previously demonstrated that
      the beta-domain amino acid sequence dictates the transcriptional properties of
      Pit-1beta. Here, we show that five hydrophobic beta-domain residues are required
      for Pit-1 isoform-specific repression of Ras signaling, and we demonstrate that
      sodium butyrate and trichostatin A, pharmacological inhibitors of histone
      deacetylation, as well as viral Ski protein, a dominant-negative inhibitor of
      recruitment of N-CoR/mSin3 histone deacetylase complexes, specifically reverse
      beta isoform-specific repression of Ras signaling. Moreover, we directly
      demonstrate, with a chromatin immunoprecipitation assay, that the Pit-1beta
      isoform alters the histone acetylation state of the proximal prolactin promoter.
      This differential analysis of Pit-1/Pit-1beta isoform function provides
      significant insights into the structural determinants that govern how different
      transcription factors with identical DNA sequence specificity can display
      opposite effects on target gene activity.

PMID- 10921929
TI  - Interactions between Spc2p and other components of the endoplasmic reticulum
      translocation sites of the yeast Saccharomyces cerevisiae.
AB  - In yeast, the endoplasmic reticulum membrane proteins Sec11p and Spc3p are
      essential for the cleavage of signal peptides of nascent polypeptide chains
      during their passage through translocation sites. Genetic and biochemical
      experiments demonstrate that Sec11p and Spc3p are tightly associated with two
      other proteins, Spc1p and Spc2p, whose functions are largely unknown. Using anti
      Spc2p antibodies, we show here that this heterotetrameric complex associates with
      Sbh1p and Sbh2p, the beta-subunits of the Sec61p complex and the Ssh1p complex,
      respectively. Depletion of Spc2p decreased the enzymatic activity of the SPC in
      vitro, led to a loss of Spc1p, and led to a down-regulation of the amount of
      Sec11p and Spc3p in the endoplasmic reticulum. Moreover, the deletion of Spc2p
      also decreased the expression level of Sbh2p. These data implicate that Spc2p not
      only enhances the enzymatic activity of the SPC but also facilitates the
      interactions between different components of the translocation site.

PMID- 10921927
TI  - Release of signal peptide fragments into the cytosol requires cleavage in the
      transmembrane region by a protease activity that is specifically blocked by a
      novel cysteine protease inhibitor.
AB  - Signal peptides of secretory and membrane proteins are generated by proteolytic
      processing of precursor proteins after insertion into the endoplasmic reticulum
      membrane. Liberated signal peptides can be further processed, and the resulting N
      terminal fragments are released toward the cytosol, where they may interact with
      target proteins like calmodulin. We show here that the processing of signal
      peptides requires a protease activity distinct from signal peptidase. This
      activity is inhibited specifically with a newly developed cysteine protease
      inhibitor, 1, 3-di-(N-carboxybenzoyl-l-leucyl-l-leucyl)amino acetone ((Z-LL)(2)
      ketone). Inhibitor studies revealed that the final, (Z-LL)(2) ketone-sensitive
      cleavage event occurs within the hydrophobic transmembrane region of the signal
      peptide, thus promoting the release of an N-terminal fragment into the cytosol.

PMID- 10921930
TI  - Yrb1p interaction with the gsp1p C terminus blocks Mog1p stimulation of GTP
      release from Gsp1p.
AB  - Mog1p, a multicopy suppressor of gsp1, the temperature-sensitive mutant of the
      Saccharomyces cerevisiae Ran homologue, binds to GTP-Gsp1p but not to GDP-Gsp1p.
      The function of Mog1p in the Ran cycle is as yet unknown. This study found that
      Mog1p releases a nucleotide from GTP-Gsp1p but not from GDP-Gsp1p. Yrb1p, the S.
      cerevisiae homologue of RanBP1, which is a strong inhibitor of RCC1-stimulated
      nucleotide release, also inhibited the Mog1p-stimulated nucleotide release from
      GTP-Gsp1p. At a concentration corresponding to the molar concentration of GTP
      Gsp1p, Yrb1p completely inhibited the Mog1p-stimulated nucleotide release.
      Consistently, the Yrb1p.GTP-Gsp1p complex was more stable than the Mog1p.GTP
      Gsp1p complex. Yrb1p did not inhibit the Mog1p-stimulated nucleotide release from
      GTP-Gsp1DeltaC. The Gsp1DeltaC protein lacks the final eight amino acids of the C
      terminus, and for this reason, the interaction between GTP-Gsp1DeltaC and Yrb1p
      was strongly reduced. On the other hand, Mog1p binds to GTP-Gsp1DeltaC more
      efficiently than to GTP-Gsp1p.

PMID- 10921931
TI  - Comparison and application of a novel genotyping method, semiautomated primer
      specific and mispair extension analysis, and four other genotyping assays for
      detection of hepatitis C virus mixed-genotype infections.
AB  - To date the true prevalence of hepatitis C virus (HCV) mixed-genotype infections
      has not been established mainly because currently available methods are not
      suitable for the detection of mixed genotypes in a viral population. A novel
      semiautomated genotyping method, primer-specific and mispair extension analysis
      (S-PSMEA), which is more reliable than other genotyping assays was developed for
      detection of HCV mixed-genotype infections. A genotype present at levels as low
      as 0.8% in a defined mix of HCV genotypes was detected, showing a 20-fold
      increase in sensitivity over that of direct DNA sequencing. A total of 434 HCV
      isolates were genotyped and analyzed for a comparative study of the accuracy
      between S-PSMEA and four current genotyping methods. The results showed that
      viruses in approximately 40% of the samples from this group determined to be
      infected with mixed genotypes by S-PSMEA were undetected by direct DNA sequencing
      due to its low sensitivity. Type-specific PCR, line probe assay, and restriction
      fragment length polymorphism analysis performed poorly, being able to identify
      only 38.5, 16.1, and 15.4% of mixed-genotype infections, respectively, that were
      detected by direct DNA sequencing. The prevalence of mixed-genotype infections
      detected by S-PSMEA was 7.9% (12 of 152 donors) among HCV-infected blood donors,
      14.3% (15 of 105) among patients with chronic hepatitis C, and 17.1% (6 of 36)
      among thalassemia patients who had received multiple transfusions. The data lead
      us to conclude that HCV mixed-genotype infections are more common than previously
      estimated and that S-PSMEA may be the method of choice when detection of
      genotypes present at low levels in mixed-genotype infections is required due to
      its higher level of sensitivity.

PMID- 10921932
TI  - Rapid automated antimicrobial susceptibility testing of Streptococcus pneumoniae
      by use of the bioMerieux VITEK 2.
AB  - The VITEK 2 is a new automated instrument for rapid organism identification and
      susceptibility testing. It has the capability of performing rapid susceptibility
      testing of Streptococcus pneumoniae with specially configured cards that contain
      enriched growth medium and antimicrobial agents relevant for this organism. The
      present study compared the results of testing of a group of 53 challenge strains
      of pneumococci with known resistance properties and a collection of clinical
      isolates examined in two study phases with a total of 402 and 416 isolates,
      respectively, with a prototype of the VITEK 2. Testing was conducted in three
      geographically separate laboratories; the challenge collection was tested by all
      three laboratories, and the unique clinical isolates were tested separately by
      the individual laboratories. The VITEK 2 results of tests with 10 antimicrobial
      agents were compared to the results generated by the National Committee for
      Clinical Laboratory Standards reference broth microdilution MIC test method.
      Excellent interlaboratory agreement was observed with the challenge strains. The
      overall agreement within a single twofold dilution of MICs defined by the VITEK 2
      and reference method with the clinical isolates was 96.3%, although there were a
      number of off-scale MICs that could not be compared. The best agreement with the
      clinical isolates was achieved with ofloxacin and chloramphenicol (100%), and the
      lowest level of agreement among those drugs with sufficient on-scale MICs
      occurred with trimethoprim-sulfamethoxazole (89.7%). Overall there were 1.3% very
      major, 6.6% minor, and no major interpretive category errors encountered with the
      clinical isolates, although >80% of the minor interpretive errors involved only a
      single log(2) dilution difference. The mean time for generation of susceptibility
      results with the clinical isolates was 8.1 h. The VITEK 2 provided rapid,
      reliable susceptibility category determinations with both the challenge and
      clinical isolates examined in this study.

PMID- 10921934
TI  - Clinical and financial benefits of rapid detection of respiratory viruses: an
      outcomes study.
AB  - To assess the expected benefits of rapid reporting of respiratory viruses, we
      compared patients whose samples were processed using standard techniques such as
      enzyme immunoassays, shell vial assays, and culture tube assays (year 1) to
      patients whose samples were processed with the same standard techniques in
      addition to immunofluorescent testing (FA) directly on cytocentrifuged samples
      (year 2). The cytospin FA screened for influenza A and B viruses, respiratory
      syncytial virus (RSV), parainfluenza viruses 1 to 3, and adenovirus (DAKO
      Diagnostics Ltd.). The specificity of the cytospin FA for all viruses was 100%.
      The sensitivities for influenza A virus and RSV were 90 and 98%, respectively,
      but the sensitivities for influenza B virus and adenovirus were unacceptable
      (14.3 and 0%, respectively). However, since the former viruses account for >85%
      of our isolates from clinical specimens, the cytospin FA is an excellent
      screening test since the positive result was available within hours. The mean
      turnaround time for all positive viruses was 4.5 days in year 1 and 0.9 day in
      year 2 (P = 0.001). This rapid reporting resulted in physicians having access to
      information sooner, enabling more appropriate treatment. The mean length of stay
      in the hospital for inpatients with respiratory viral isolates was 10.6 days for
      year 1 versus 5.3 days for year 2. Mean variable costs for these patients was
      $7,893 in year 1 and $2,177 in year 2. After subtracting reagent costs and
      technological time, the savings in variable costs was $144,332/year. Summarizing,
      the cytospin FA markedly decreased turnaround time and was associated with
      decreased mortality, length of stay, and costs and with better antibiotic
      stewardship.

PMID- 10921933
TI  - Nationwide German multicenter study on prevalence of antibiotic resistance in
      staphylococcal bloodstream isolates and comparative in vitro activities of
      quinupristin-dalfopristin.
AB  - Antibiotic-resistant gram-positive bacteria have become an increasing problem in
      the last two decades. In order to evaluate the prevalence of antibiotic
      resistance in staphylococcal bloodstream isolates in Germany, 2,042 staphylococci
      collected in 21 tertiary-care hospitals were investigated during a 3-year period
      (March 1996 to March 1999). Altogether, 1,448 S. aureus isolates and 594
      coagulase-negative staphylococci (CoNS) that comprised 13 different species were
      included. Furthermore, the antistaphylococcal activities of quinupristin
      dalfopristin were compared with those of eight other compounds by the broth
      microdilution method. The rates of oxacillin resistance in Staphylococcus aureus,
      S. epidermidis, S. haemolyticus, and other CoNS were 13.5, 69, 90, and 34%,
      respectively. In oxacillin-resistant strains high rates of resistance (up to
      100%) to erythromycin, clindamycin, ciprofloxacin, and gentamicin were also
      observed. However, no strain appeared to be resistant to vancomycin or
      quinupristin-dalfopristin. The streptogramin combination exhibited excellent in
      vitro activity against all staphylococcal species tested, regardless of the
      patterns of resistance to other drug classes. In terms of MICs at which 90% of
      the isolates are inhibited, quinupristin-dalfopristin was 2 times more active
      against S. aureus isolates, 4 to 16 times more active against S. haemolyticus,
      and 8 to 32 times more active against S. epidermidis than vancomycin or
      teicoplanin.

PMID- 10921935
TI  - Rapid identification of Candida dubliniensis using a species-specific molecular
      beacon.
AB  - Candida dubliniensis is an opportunistic fungal pathogen that has been linked to
      oral candidiasis in AIDS patients, although it has recently been isolated from
      other body sites. DNA sequence analysis of the internal transcribed spacer 2
      (ITS2) region of rRNA genes from reference Candida strains was used to develop
      molecular beacon probes for rapid, high-fidelity identification of C.
      dubliniensis as well as C. albicans. Molecular beacons are small nucleic acid
      hairpin probes that brightly fluoresce when they are bound to their targets and
      have a significant advantage over conventional nucleic acid probes because they
      exhibit a higher degree of specificity with better signal-to-noise ratios. When
      applied to an unknown collection of 23 strains that largely contained C. albicans
      and a smaller amount of C. dubliniensis, the species-specific probes were 100%
      accurate in identifying both species following PCR amplification of the ITS2
      region. The results obtained with the molecular beacons were independently
      verified by random amplified polymorphic DNA analysis-based genotyping and by
      restriction enzyme analysis with enzymes BsmAI and NspBII, which cleave
      recognition sequences within the ITS2 regions of C. dubliniensis and C. albicans,
      respectively. Molecular beacons are promising new probes for the rapid detection
      of Candida species.

PMID- 10921937
TI  - Evaluation of recA sequences for identification of Mycobacterium species.
AB  - 16S rRNA sequence data have been used to provide a molecular basis for an
      accurate system for identification of members of the genus Mycobacterium.
      Previous studies have shown that Mycobacterium species demonstrate high levels
      (>94%) of 16S rRNA sequence similarity and that this method cannot differentiate
      between all species, i.e., M. gastri and M. kansasii. In the present study, we
      have used the recA gene as an alternative sequencing target in order to
      complement 16S rRNA sequence-based genetic identification. The recA genes of 30
      Mycobacterium species were amplified by PCR, sequenced, and compared with the
      published recA sequences of M. tuberculosis, M. smegmatis, and M. leprae
      available from GenBank. By recA sequencing the species showed a lower degree of
      interspecies similarity than they did by 16S rRNA gene sequence analysis, ranging
      from 96.2% between M. gastri and M. kansasii to 75.7% between M. aurum and M.
      leprae. Exceptions to this were members of the M. tuberculosis complex, which
      were identical. Two strains of each of 27 species were tested, and the
      intraspecies similarity ranged from 98.7 to 100%. In addition, we identified new
      Mycobacterium species that contain a protein intron in their recA genes, similar
      to M. tuberculosis and M. leprae. We propose that recA gene sequencing offers a
      complementary method to 16S rRNA gene sequencing for the accurate identification
      of the Mycobacterium species.

PMID- 10921936
TI  - Performance characteristics of the QUANTIPLEX HIV-1 RNA 3.0 assay for detection
      and quantitation of human immunodeficiency virus type 1 RNA in plasma.
AB  - The QUANTIPLEX HIV-1 RNA assay, version 3.0 (a branched DNA, version 3.0, assay
      [bDNA 3.0 assay]), was evaluated by analyzing spiked and clinical plasma samples
      and was compared with the AMPLICOR HIV-1 MONITOR Ultrasensitive (ultrasensitive
      reverse transcription-PCR [US-RT-PCR]) method. A panel of spiked plasma samples
      that contained 0 to 750,000 copies of human immunodeficiency virus type 1 (HIV-1)
      RNA per ml was tested four times in each of four laboratories (1,344 assays).
      Negative results (<50 copies/ml) were obtained in 30 of 32 (94%) assays with
      seronegative samples, 66 of 128 (52%) assays with HIV-1 RNA at 50 copies/ml, and
      5 of 128 (4%) assays with HIV-1 RNA at 100 copies/ml. The assay was linear from
      100 to 500,000 copies/ml. The within-run standard deviation (SD) of the log(10)
      estimated HIV-1 RNA concentration was 0.08 at 1,000 to 500,000 copies/ml,
      increased below 1,000 copies/ml, and was 0.17 at 100 copies/ml. Between-run
      reproducibility at 100 to 500 copies/ml was <0.10 log(10) in most comparisons.
      Interlaboratory differences across runs were </=0.10 log(10) at all
      concentrations examined. A subset of the panel (25 to 500 copies/ml) was also
      analyzed by the US-RT-PCR assay. The within-run SD varied inversely with the
      log(10) HIV-1 RNA concentration but was higher than the SD for the bDNA 3.0 assay
      at all concentrations. Log-log regression analysis indicated that the two methods
      produced very similar estimates at 100 to 500 copies/ml. In parallel testing of
      clinical specimens with low HIV-1 RNA levels, 80 plasma samples with <50
      copies/ml by the US-RT-PCR assay had <50 copies/ml when they were retested by the
      bDNA 3.0 assay. In contrast, 11 of 78 (14%) plasma samples with <50 copies/ml by
      the bDNA 3.0 assay had >/=50 copies/ml when they were retested by the US-RT-PCR
      assay (median, 86 copies/ml; range, 50 to 217 copies/ml). Estimation of bDNA 3.0
      values of <50 copies/ml by extending the standard curve of the assay showed that
      these samples with discrepant results had higher HIV-1 RNA levels than the
      samples with concordant results (median, 34 versus 17 copies/ml; P = 0.0051 by
      the Wilcoxon two-sample test). The excellent reproducibility, broad linear range,
      and good sensitivity of the bDNA 3.0 assay make it a very attractive method for
      quantitation of HIV-1 RNA levels in plasma.

PMID- 10921938
TI  - vacA genotypes in Helicobacter pylori strains isolated from children with and
      without duodenal ulcer in Brazil.
AB  - Data concerning the association between vacA genotypes and disease in children in
      both developed and developing countries are scarce, especially because of the
      small number of children with a duodenal ulcer studied. The vacA genotypes of
      Helicobacter pylori strains obtained from 65 children (24 with a duodenal ulcer
      and 41 without a duodenal ulcer; 33 girls; mean age, 10.2 years; age range, 1 to
      17 years) were investigated as described by J. C. Atherton et al. (J. Clin.
      Microbiol. 37:2979-2982, 1999). Ten (15.4%) children were infected with more than
      one H. pylori strain. None of these patients were included in our analysis of the
      relationship between gastric disorders and specific vacA genotypes. The s1 allele
      was detected in all H. pylori strains isolated from patients with a duodenal
      ulcer and from 21 (58.3%) patients without a duodenal ulcer (P = 0.003). Strains
      with the s2 allele were found only in patients without ulcer (n = 15; 41.7%).
      Most s1 strains had the s1b allele (97.5%), a result similar to that reported for
      adults from the Iberian peninsula, which could reflect the Brazilian population
      origin. One untypeable s1 strain was isolated. The m1 allele was also more
      frequently found in strains obtained from duodenal ulcer patients (P = 0.028).
      The m2 allele was found in strains obtained from 20 (36. 4%) children, 3 (15.8%)
      with an ulcer and 17 (47.2%) without an ulcer. Only one m hybrid strain (m1 and
      m2 hybrid) was detected. It was demonstrated for the first time that the
      frequencies of colonization with strains with the s1 allele (14.3% in children up
      to 8 years of age and 85.7% in older patients; P = 0.012) and of strains with the
      m1 allele (11.1% in patients up to the age 8 years and 88.9% in older children; P
      = 0.013) increase with age.

PMID- 10921939
TI  - Proteases as markers for differentiation of pathogenic and nonpathogenic species
      of Acanthamoeba.
AB  - Acanthamoeba keratitis is a vision-threatening infection caused by pathogenic
      species of the genus Acanthamoeba. Although not all Acanthamoeba spp. can cause
      keratitis, it is important to differentiate pathogenic species and isolates from
      nonpathogens. Since extracellular proteases may play a role in ocular pathology,
      we used colorimetric, cytopathic, and zymographic assays to assess extracellular
      protease activity in pathogenic and nonpathogenic Acanthamoeba. Colorimetric
      assays, using azo-linked protein as a substrate, showed extracellular protease
      activity in Acanthamoeba-conditioned medium and differentiated pathogenic and
      nonpathogenic Acanthamoeba. Monolayers of immortalized corneal epithelial cells
      in four-well plates were used for cytopathic effect (CPE) assays. Pathogenic
      Acanthamoeba isolates exhibited marked CPE on immortalized corneal epithelial
      cells, while nonpathogenic isolates did not exhibit CPE. Protease zymography was
      performed with Acanthamoeba-conditioned medium as well as with Acanthamoeba- plus
      epithelial-cell-conditioned medium. The zymographic protease assays showed
      various banding patterns for different strains of Acanthamoeba. In pathogenic
      Acanthamoeba isolates, all protease bands were inhibited by phenylmethylsulfonyl
      fluoride (PMSF), suggesting serine type proteases, while in nonpathogenic strains
      only partial inhibition was observed by using PMSF. The pathogenic Acanthamoeba
      strains grown under typical laboratory conditions without epithelial cells
      exhibited one overexpressed protease band of 107 kDa in common; this protease was
      not observed in nonpathogenic Acanthamoeba strains. The 107-kDa protease
      exhibited activity over a pH range of 5 to 9.5.

PMID- 10921941
TI  - Detection of significant bacteriuria by automated urinalysis using flow
      cytometry.
AB  - A new flow cytometry-based automated urine analyzer, the UF-50, was evaluated for
      its ability to screen urine samples for significant bacteriuria. One hundred
      eighty-six urine specimens from patients attending an outpatient clinic of a
      university-based hospital were examined. The results obtained with the UF-50 were
      compared with those obtained by conventional quantitative urine culture. The UF
      50 detected significant bacteriuria with a sensitivity of 83.1%, a specificity of
      76.4%, a positive predictive value of 62.0%, a negative predictive value of
      90.7%, and an accuracy of 78.5%. These results are comparable to those obtained
      by previously reported screening procedures. Besides detecting significant
      bacteriuria, the UF-50 can also perform routine urinalysis, including measurement
      of concentrations of red blood cells, white blood cells, epithelial cells, and
      casts, within 70 s. This capability renders this new flow cytometry-based urine
      analyzer superior to previously reported rapid screening methods.

PMID- 10921940
TI  - Relative abundance of oligosaccharides in Candida species as determined by
      fluorophore-assisted carbohydrate electrophoresis.
AB  - Fluorophore-assisted carbohydrate electrophoresis (FACE) is a straightforward,
      sensitive method for determining the presence and relative abundance of
      individual oligomannosyl residues in Candida mannoprotein, the major antigenic
      determinant located on the outer surface of the yeast cell wall. The single
      terminal aldehydes of oligomannosyl residues released by hydrolysis were tagged
      with the charged fluorophore 8-aminonaphthalene-1,3,6-trisulfonate (ANTS) and
      separated with high resolution on the basis of size by polyacrylamide gel
      electrophoresis. ANTS fluorescence labeling was not biased by oligomannoside
      length; therefore, band fluorescence intensity was directly related to the
      relative abundance of individual oligomannoside moieties in heterogeneous
      samples. FACE analysis revealed the major oligomannosides released by acid
      hydrolysis and beta-elimination of Fehling-precipitated mannan from Candida
      albicans, which were the same as those previously reported in studies based on
      mass and nuclear magnetic spectroscopic analysis. FACE was also amenable to the
      analysis of samples obtained by direct hydrolysis of whole yeast cells. Whole
      cell acid hydrolysis and whole-cell beta-elimination of two isolates each of C.
      albicans, C. glabrata, C. krusei, C. lusitaniae, C. parapsilosis, C. rugosa, C.
      stellatoidea, and C. tropicalis resulted in oligomannoside gel banding patterns
      that were species and strain specific for the 16 isolates surveyed. Whereas some
      bands were specific for an individual isolate or species, other bands were shared
      by two or three species in various groupings. Differences in the mannoprotein
      composition of C. albicans A9 and four spontaneous cell surface mutants were also
      detected. Mannan "fingerprints," or banding pattern profiles, derived from the
      electrophoretic mobilities of individual bands relative to the migration of acid
      hydrolyzed dextran (relative migration index) yielded profiles characteristic of
      individual isolates not revealed by standard assimilation and biochemical
      profiles. FACE represents an accessible, sensitive, and quantitative analytical
      tool enabling the characterization of yeast mannan complexity.

PMID- 10921942
TI  - Enteric virus infections and diarrhea in healthy and human immunodeficiency virus
      infected children.
AB  - Forty-three stool samples from 27 human immunodeficiency virus (HIV)-seropositive
      children and 38 samples from 38 HIV-negative children, collected during a 15
      month period, were examined for enteric viruses. Diagnostic assays included
      enzyme immunoassays for rotavirus, adenovirus, and Norwalk virus; polyacrylamide
      gel electrophoresis for picobirnavirus and atypical rotavirus; and PCR for
      astrovirus and enterovirus. Specimens from HIV-positive children were more likely
      than those of HIV-negative children to have enterovirus (56 versus 21%; P <
      0.0002) and astrovirus (12 versus 0%; P < 0.02), but not rotavirus (5 versus 8%;
      P > 0.5). No adenoviruses, picobirnaviruses, or Norwalk viruses were found. The
      rates of virus-associated diarrhea were similar among HIV-positive and HIV
      negative children. Enteroviruses were excreted for up to 6 months in HIV-positive
      children; however, no evidence for prolonged excretion of poliovirus vaccine was
      observed. These results suggest that although infection with enterovirus and
      astrovirus may be frequent in HIV-infected children, enteric viruses are not
      associated with the diarrhea frequently suffered by these children.

PMID- 10921943
TI  - Detection of complement-mediated antibody-dependent bactericidal activity in a
      fluorescence-based serum bactericidal assay for group B Neisseria meningitidis.
AB  - Serum bactericidal assays (SBAs) for Group B meningococci are considered the
      methods of choice for the evaluation of functional antimeningococcal antibodies.
      Many investigators regard SBAs as time- and labor-intensive. Variations in SBA
      protocols among different laboratories make interpretation of results difficult.
      Here we describe a fluorescence-based serum bactericidal assay (fSBA) and compare
      the results obtained with the fSBA to the results obtained with a more
      conventional SBA. The results generated by both assays were dependent upon the
      surviving bacteria after incubation, and the assay mixtures contained identical
      components. Differences between assays lie in how the surviving bacteria are
      quantified. The fSBA described in the paper uses the fluorescent dye alamarBlue
      (M. V. Lancaster and R. D. Fields, U.S. patent 5501959, March 1996). The
      fluorescent signals generated in the fSBA correlate to the oxidative respiration
      of surviving bacteria. Viable bacteria were detected between 6 and 8 h directly
      from reaction mixtures in 96-well plates by the fSBA, whereas colonies isolated
      on semisolid media could be counted after 24 h of incubation. The bactericidal
      titers generated by both assays were nearly identical. The fSBA described here
      can be used as an assay for the screening of large quantities of individual sera
      as complement sources or as a method for the detection of functional antibodies
      directed against group B Neisseria meningitidis in both human and mouse antisera.

PMID- 10921944
TI  - PCR fragment length polymorphism analysis of vancomycin-resistant Enterococcus
      faecium.
AB  - In this study, the glycopeptide resistance element, Tn1546, in 124 VanA
      Enterococcus faecium clinical isolates from 13 Michigan hospitals was evaluated
      using PCR fragment length polymorphism. There were 26 pulsed-field gel
      electrophoresis (PFGE) types, which consisted of epidemiologically related and
      unrelated isolates from separate patients (1992 to 1996). Previously published
      oligonucleotides specific for regions in the vanA gene cluster of Tn1546 were
      used to amplify vanRS, vanSH, vanHAX, vanXY, and vanYZ. The glycopeptide
      resistance element, Tn1546, of E. faecium 228 was used as the basis of comparison
      for all the isolates in this study. Five PCR fragment length patterns were found,
      as follows. (i) PCR amplicons were the same size as those of EF228 for all genes
      in the vanA cluster in 19.4% of isolates. (ii) The PCR amplicon for vanSH was
      larger than that of EF228 (3.7 versus 2.3 kb) due to an insertion between the
      vanS and vanH genes (79.2% of isolates). (iii) One isolate in a unique PFGE group
      had a vanSH amplicon larger than that of EF228 (5.7 versus 2.3 kb) due to an
      insertion in the vanS gene and an insertion between the vanS and vanH genes. (iv)
      One isolate did not produce a vanSH amplicon, but when vanS and vanH were
      amplified separately, both amplicons were the same size as those as EF228. (v)
      One isolate had a vanYZ PCR product larger than that of EF228 (2.8 versus 1.6
      kb). This study shows that in a majority of the VanA E. faecium isolates, Tn1546
      is altered compared to that of EF228. A total of 79.2% of the study isolates had
      the same-size insertion between the vanS and vanH genes. The results of this
      study show dissemination of an altered Tn1546 in heterologous VanA E. faecium in
      Michigan hospitals.

PMID- 10921945
TI  - Nosocomial transmission of echovirus 30: molecular evidence by phylogenetic
      analysis of the VP1 encoding sequence.
AB  - We investigated six cases of enterovirus infection in a neonatal unit. The index
      patient, a 5-day-old boy, was admitted with aseptic meningitis due to echovirus
      30 (E30). Secondary infections with E30 occurred in five babies. Comparison of
      the complete VP1 sequences showed that the isolates recovered from the index
      patient and his mother were closely related to those recovered from the five
      babies with secondary infections, demonstrating a nosocomial transmission of the
      virus. In the phylogenetic tree reconstructed from the VP1 sequences, the
      isolates formed a monophyletic cluster related to an E30 strain collected in June
      1997 during an outbreak of aseptic meningitis.

PMID- 10921946
TI  - Estimation of minimum sterol 14alpha-demethylation-inhibitory concentration of
      azoles in Candida yeasts using acetate-mediated growth inhibition: potential
      utility in susceptibility testing.
AB  - We have recently shown that 14alpha-demethylation-deficient cells of Candida
      albicans are subject to growth arrest by 0.24 M acetate in a yeast extract
      peptone-glucose medium and that the minimum concentration of an azole antifungal
      agent required for total inhibition of sterol 14alpha-demethylation (MDIC for
      minimum demethylation-inhibitory concentration) is practically identical to its
      MIC determined in the acetate-supplemented medium (O. Shimokawa and H. Nakayama,
      Antimicrob. Agents Chemother. 43:100-105, 1999). In the present study we
      estimated the MDICs of three different azoles (fluconazole, ketoconazole, and
      itraconazole) for strains of various Candida species using this method and
      compared them with the MICs determined in the corresponding acetate-free medium.
      The results demonstrated that the test strains were divided into two classes. One
      class of strains was characterized by tolerance to 14alpha-demethylation
      deficiency (MIC > MDIC) and consisted of strains of C. albicans, C.
      guilliermondii, C. kefyr, and C. tropicalis. The other class was intolerant to
      14alpha-demethylation deficiency (MIC approximately MDIC) and comprised strains
      of C. glabrata, C. krusei, and C. parapsilosis. We also showed that replacement
      of the yeast extract-peptone-glucose medium with RPMI 1640 medium did not affect
      the results substantially. Furthermore, the 80% inhibitory concentration (IC(80))
      in RPMI 1640 medium, recommended as a substitute for the conventional MIC in
      susceptibility testing, was found to be close to the MDIC.

PMID- 10921947
TI  - Development of a quantitative real-time detection assay for hepatitis B virus DNA
      and comparison with two commercial assays.
AB  - A highly reproducible and sensitive real-time detection assay based on TaqMan
      technology was developed for the detection of hepatitis B virus (HBV) DNA and
      compared with two commercially available assays. The assay was validated with the
      Viral Quality Control panel, which also includes EUROHEP HBV DNA standards. This
      real-time PCR detection system had a dynamic range of 373 to 10(10) genome copies
      per ml and showed an excellent correlation with both the commercial HBV Digene
      Hybrid Capture II microplate assay (Digene Diagnostics) and the HBV MONITOR assay
      (Roche Diagnostics). To demonstrate its clinical utility, four chronically HBV
      infected patients treated with lamuvidine were monitored using the three
      different assays. From the results we concluded that this assay is an excellent
      alternative for monitoring of HBV-infected patients in routine diagnostics and
      clinical practice, enabling the analysis of a large dynamic range of HBV DNA in a
      single, undiluted sample.

PMID- 10921948
TI  - Rapid detection and identification of Candida, Aspergillus, and Fusarium species
      in ocular samples using nested PCR.
AB  - A protocol for the rapid detection of fungal DNA in ocular samples, derived from
      three species, Candida albicans, Aspergillus fumigatus, and Fusarium solani, has
      been developed. Two novel panfungal primers complementary to 18S rRNA sequences
      present in all three species were designed. Panfungal PCR was followed by three
      nested PCRs utilizing species-specific primers. PCR sensitivity ranged from 50 to
      100 fg of free DNA and between one and two C. albicans organisms. In addition, we
      also developed a rapid and reliable DNA extraction protocol. This protocol
      minimized DNA loss during extraction, whilst removing compounds from vitreous and
      aqueous fluids that have previously been shown to have inhibitory effects on PCR.
      Preliminary results obtained after testing the protocol on three patient samples
      support culture results and medical history. However, one patient was PCR
      positive but culture negative, suggesting that the sensitivity of this protocol
      may exceed that of traditional culture techniques. This system, therefore,
      constitutes an additional protocol that may significantly aid patient management
      in cases where fungal endophthalmitis is suspected.

PMID- 10921949
TI  - Comparison of an established antibody sandwich method with an inhibition method
      of Histoplasma capsulatum antigen detection.
AB  - The Histoplasma antigen immunoassay utilizes an antibody sandwich method that
      provides a rapid and reliable means of diagnosing the more severe forms of
      histoplasmosis. Inhibition assays have been developed for antigen detection and
      offer at least one potential advantage, namely, reduced antibody requirements. We
      have developed an inhibition assay using the polyclonal antibody employed in our
      standard sandwich assay. Urine and serum specimens from patients with culture
      proven histoplasmosis and controls were tested using both methods. The two
      methods had similar sensitivities for detection of antigen in urine (antibody
      sandwich = 92.5% versus inhibition = 87.5%, P = 0.500) and serum (82.5% versus
      80.0%, P = 1. 000). With serum, the specificities of both methods were similar
      (antibody sandwich assay = 95.0% versus inhibition assay = 92.5%, P = 1.000), and
      with urine, the specificity of the antibody sandwich method was superior (97.5%
      versus 80.0%, P = 0.039). While the overall reproducibility of both methods was
      excellent (with urine, antibody sandwich assay intraclass correlation coefficient
      = 0.9975 and with serum = 0.9949; correlation coefficient of the inhibition assay
      with urine = 0.9736 and with serum = 0.9850), that of the inhibition method was
      only fair to poor for the controls: urine = -0. 0152, serum = 0.5595.
      Reproducibility was good for the controls using the sandwich method: urine =
      0.7717, serum = 0.9470. Cross-reactivity was observed in specimens from patients
      infected with Blastomyces dermatitidis, Paracoccidioides brasiliensis, and
      Penicillium marneffei. In conclusion, the decreased specificity and inferior
      reproducibility with control specimens suggest that the inhibition assay has
      poorer precision toward the lower end of the detection range.

PMID- 10921950
TI  - Use of the neisserial lipoprotein (Lip) for subtyping Neisseria gonorrhoeae.
AB  - The pathogenic Neisseria species N. meningitidis and N. gonorrhoeae possess an
      outer membrane lipoprotein, designated Lip, which is present in all strains
      tested. The predicted protein sequence of Lip consists of a consensus AAEAP amino
      acid repeat. The objective of this study was to determine the feasibility of
      using the Lip repeat number and sequence for subtyping of Neisseria gonorrhoeae.
      The lip genes of each isolate were amplified by PCR and sequenced to determine
      the repeat number and sequence. Among the 46 strains we examined, eight different
      Lip repeat numbers were identified, with lengths of 11 (1 strain), 12 (14
      strains), 13 (2 strains), 14 (10 strains), 15 (5 strains), 16 (10 strains), 17 (3
      strains), and 20 (1 strain) repeats. Analysis indicated differences in the
      sequences within the repeats that resulted in amino acid alterations in repeat
      classes that contained multiple strains. Among the 46 isolates examined, we were
      able to identify 17 unique Lip subtyping patterns.

PMID- 10921951
TI  - Sequence analysis of the ank gene of granulocytic ehrlichiae.
AB  - The ank gene of the agent of human granulocytic ehrlichiosis (HGE) codes for a
      protein with a predicted molecular size of 131.2 kDa that is recognized by serum
      from both dogs and humans infected with granulocytic ehrlichiae. As part of an
      effort to assess the phylogenetic relatedness of granulocytic ehrlichiae from
      different geographic regions and in different host species, the ank gene was PCR
      amplified and sequenced from a variety of sources. These included 10 blood
      specimens from patients with confirmed human granulocytic ehrlichiosis (three
      from New York, four from Wisconsin, two from Slovenia, and one from Sweden). Also
      examined was a canine granulocytic ehrlichia sample obtained from Minnesota,
      Ehrlichia equi from California, Ehrlichia phagocytophila from Sweden, and the
      granulocytic ehrlichia isolate USG3. The sequences showed a high level of
      homology (>95.5% identity), with the lowest homology occurring between a New York
      HGE agent and the Swedish E. phagocytophila. Several 3-bp deletions and a
      variable number of 51- and 81-bp direct repeats were noted. Although the North
      American HGE sequences showed the highest conservation (>98.1% identity),
      phylogenetic analyses indicated that these samples represent two separate clades,
      one including the three New York HGE samples and the USG3 strain and another with
      the Wisconsin HGE and Minnesota canine sequences. Two of the New York samples and
      the USG3 strain showed 100% identity over the entire 3,696-bp product. Likewise,
      three of the Wisconsin human samples and the Minnesota dog sample were identical
      (3,693 bp). Whereas phylogenetic analysis showed that the E. equi sequence was
      most closely related to the Upper Midwest samples, analysis of the repeat
      structures showed it to be more similar to the European samples. Overall, the
      genetic analysis based on the ank gene showed that the granulocytic ehrlichiae
      are closely related, appear to infect multiple species, and can be grouped into
      at least three different clades, two North American and one European.

PMID- 10921952
TI  - Mapping of IS6110 insertion sites in two epidemic strains of Mycobacterium
      tuberculosis.
AB  - A widely distributed strain designated 210 was identified in a study of the
      diversity of Mycobacterium tuberculosis DNA fingerprints from three
      geographically separate states in the United States. This strain is characterized
      by a 21-band fingerprint pattern when probed with IS6110, and the pattern is
      similar to that displayed by strains designated W. Intracellular growth of strain
      210 isolates in human macrophages is significantly faster than that of isolates
      from other clusters or nonclustered isolates. The purpose of this study was to
      identify the sites of IS6110 insertions in strain 210 and compare these to IS6110
      insertion sites in strain W. Our hypothesis is that an IS6110 insertion site(s)
      could possibly be responsible for a strain's increased capacity for transmission
      and/or replication. In this report, the insertion sites in strains 210 and W are
      described and referenced to their location in the M. tuberculosis H37Rv genome
      sequence. The W and 210 strains have 17 identical sites of IS6110 insertion and
      additional sequence not found in H37Rv but present in other clinical isolates.
      The IS6110 insertion site in the 36-bp direct repeat (DR) region of strains 210
      and W has 15 spacers in the left flanking region. The DR region on the right side
      of IS6110 has been deleted. Five sites of insertion in strain 210 not found in
      strain W are described, as well as two unique sites in strain W. One copy of
      IS6110 was found to reside 55 bp in the ctpD gene. This gene is expressed,
      indicating that IS6110 can provide a promoter sequence for the transcription of
      genes.

PMID- 10921953
TI  - Real-time PCR for diagnosis and follow-up of Toxoplasma reactivation after
      allogeneic stem cell transplantation using fluorescence resonance energy transfer
      hybridization probes.
AB  - Toxoplasma reactivation is a life-threatening complication of allogeneic stem
      cell transplantation. A poor prognosis is probably linked to a difficult
      diagnosis, based on the detection of evidence of parasites in tissue. We
      developed a real-time PCR test using fluorescence resonance energy transfer
      hybridization probes to detect and quantify Toxoplasma gondii DNA in serum. This
      PCR test gave reproducible quantitative results over a dynamic range of from 0.75
      x 10(6) to 0.75 parasites per PCR mixture. Serial samples from four patients with
      toxoplasma reactivation were evaluated. Three patients had several consecutive
      PCR-positive samples which corresponded to </=0.75 parasites. These three
      patients became PCR negative during trimethoprim-sulfamethoxazole therapy but
      never developed clinically apparent toxoplasmosis. In contrast, one patient had
      an increasing PCR signal, from 1 to 396 parasites in 12 days, and developed
      cerebral symptoms. The parasite count decreased to 5 parasites in 3 days after
      pyrimethamine-clindamycin treatment. Real-time quantitative PCR is useful for
      diagnosis and follow-up of toxoplasma reactivation.

PMID- 10921954
TI  - Clinical evaluation of the automated COBAS AMPLICOR HCV MONITOR test version 2.0
      for quantifying serum hepatitis C virus RNA and comparison to the quantiplex HCV
      version 2.0 test.
AB  - A second-generation hepatitis C virus (HCV) quantitative assay (COBAS AMPLICOR
      HCV MONITOR Test, version 2.0; COBAS HCM-2) has been developed, with the
      intention of achieving equivalent quantification of all HCV genotypes and
      improving assay performance. To evaluate the clinical performance of COBAS HCM-2
      and its utility in predicting the response to alpha interferon treatment, sera
      from 215 chronic hepatitis C patients were analyzed and the results were compared
      with those obtained by the Quantiplex bDNA HCV RNA, version 2.0, assay (bDNA-2).
      The COBAS HCM-2 had significantly greater sensitivity than bDNA-2 (94.9 versus
      88.4%; P < 0.001) when performed with sera from chronic hepatitis C patients who
      were viremic by a qualitative PCR test. The standard deviations for the within
      run and between-run reproducibilities of COBAS HCM-2 were <0. 1 and <0.2,
      respectively, and it showed an improved linear range between genotypes with the
      threefold serial dilutions tested (r(2) = 0.986 to 0.995). The COBAS HCM-2
      results were positively correlated with the bDNA-2 results, but the values for
      COBAS HCM-2 were on average 0.96 log lower than the values for bDNA-2. The mean
      difference in quantification values between these two assays did not differ among
      samples with different genotypes (0.70 to 1.00 log). No genotype-dependent
      difference in viral load was observed. The pretreatment viral load was
      significantly lower in complete responders. By using multivariate analysis, the
      viral load 2 weeks after the initiation of alpha interferon treatment was the
      strongest predictor of a complete response. In conclusion, COBAS HCM-2
      demonstrated good sensitivity, linearity, and reproducibility and efficiency
      equal to that of bDNA-2 for the quantification of HCV genotypes 1 and 2. Hence,
      this assay provides a rapid and reliable method for the quantification of HCV RNA
      in serum and is useful for the planning of interferon treatment.

PMID- 10921955
TI  - Detection of Paracoccidioides brasiliensis in tissue samples by a nested PCR
      assay.
AB  - A nested PCR assay for the detection of Paracoccidioides brasiliensis DNA was
      evaluated, using a sequence of the immunogenic gp43 gene as a target. This gene
      encodes an outer membrane protein unique to this dimorphic fungus. DNA from six
      clinical isolates and the ATCC strain 60885 of P. brasiliensis, as well as DNA
      from closely related fungi, was examined to determine detection limits and cross
      reactions. PCR was done on DNA extracts of lung homogenates from 23
      experimentally P. brasiliensis-infected and two uninfected BALB/c mice and from
      20 Histoplasma capsulatum-infected ICR mice. The results were compared to
      quantitative cultures. A detection limit of 0.5 fg of specific DNA was determined
      using cloned plasmid DNA. In all seven P. brasiliensis isolates, the expected 196
      bp nested PCR product was found. Their sequences were 100% identical to the gp43
      gene sequence in GenBank. DNA extracts of all other, related fungi were negative.
      The PCR assay was positive in 21 out of 23 culture-positive lung homogenates with
      concentrations of 1 x 10(3) to 1.3 x 10(7) CFU of P. brasiliensis per g of lung.
      Uninfected BALB/c mice and H. capsulatum-infected mice samples gave negative
      results. The high sensitivity and specificity of this new nested PCR assay for
      the detection of P. brasiliensis in tissue samples were demonstrated. The assay
      may be useful for diagnosis in human tissue samples.

PMID- 10921956
TI  - Characterization of Bartonella clarridgeiae flagellin (FlaA) and detection of
      antiflagellin antibodies in patients with lymphadenopathy.
AB  - Cat scratch disease (CSD) is a frequent clinical outcome of Bartonella henselae
      infection in humans. Recently, two case reports indicated Bartonella clarridgeiae
      as an additional causative agent of CSD. Both pathogens have been isolated from
      domestic cats, which are considered to be their natural reservoir. B.
      clarridgeiae and B. henselae can be distinguished phenotypically by the presence
      or absence of flagella, respectively. Separation of the protein content of
      purified flagella of B. clarridgeiae by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis and immunoblot analysis indicated that the flagellar filament is
      mainly composed of a polypeptide with a mass of 41 kDa. N-terminal sequencing of
      20 amino acids of this protein revealed a perfect match to the N-terminal
      sequence of flagellin (FlaA) as deduced from the sequence of the flaA gene cloned
      from B. clarridgeiae. The flagellin of B. clarridgeiae is closely related to
      flagellins of Bartonella bacilliformis and several Bartonella-related bacteria.
      Since flagellar proteins are often immunodominant antigens, we investigated
      whether antibodies specific for the FlaA protein of B. clarridgeiae are found in
      patients with CSD or lymphadenopathy. Immunoblotting with 724 sera of patients
      suffering from lymphadenopathy and 100 healthy controls indicated specific FlaA
      antibodies in 3.9% of the patients' sera but in none of the controls. B.
      clarridgeiae FlaA is thus antigenic and expressed in vivo, providing a valuable
      tool for serological testing. Our results further indicate that B. clarridgeiae
      might be a possible etiologic agent of CSD or lymphadenopathy. However, it
      remains to be clarified whether antibodies to the FlaA protein of B. clarridgeiae
      are a useful indicator of acute infection.

PMID- 10921957
TI  - Comparison of NCCLS and 3-(4,5-dimethyl-2-Thiazyl)-2, 5-diphenyl-2H-tetrazolium
      bromide (MTT) methods of in vitro susceptibility testing of filamentous fungi and
      development of a new simplified method.
AB  - The susceptibility of 30 clinical isolates belonging to six different species of
      filamentous fungi (Aspergillus fumigatus, Aspergillus flavus, Scedosporium
      prolificans, Scedosporium apiospermum, Fusarium solani, and Fusarium oxysporum)
      was tested against six antifungal drugs (miconazole, voriconazole, itraconazole,
      UR9825, terbinafine, and amphotericin B) with the microdilution method
      recommended by the National Committee for Clinical Laboratory Standards (NCCLS)
      (M38-P). The MICs were compared with the MICs obtained by a colorimetric method
      measuring the reduction of the dye 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H
      tetrazolium bromide (MTT) to formazan by viable fungi. The levels of agreement
      between the two methods were 96 and 92% for MIC-0 (clear wells) and MIC-1 (75%
      growth reduction), respectively. The levels of agreement were always higher for
      Aspergillus spp. (97% +/- 2.5%), followed by Scedosporium spp. (87% +/- 10.3%)
      and Fusarium spp. (78% +/- 7.8%). The NCCLS method was more reproducible than the
      MTT method: 98 versus 95% for MIC-0 and 97 versus 90% for MIC-1. However, the
      percentage of hyphal growth as determined visually by the NCCLS method showed
      several discrepancies when they were compared with the percentages of MTT
      reduction. A new simplified assay that incorporates the dye MTT with the initial
      inoculum and in which the fungi are incubated with the dye for 48 h or more was
      developed, showing comparable levels of agreement and reproducibility with the
      other two methods. Furthermore, the new assay was easier to perform and more
      sensitive than the MTT method.

PMID- 10921958
TI  - Application of a reverse transcription-PCR for identification and differentiation
      of Aichi virus, a new member of the Picornavirus family associated with
      gastroenteritis in humans.
AB  - Aichi viruses isolated in Vero cells from seven patients in five gastroenteritis
      outbreaks in Japan, five Japanese returning from Southeast Asian countries, and
      five local children in Pakistan with gastroenteritis were examined for
      differentiation based on their reactivities with a monoclonal antibody to a
      standard strain (A846/88) and a reverse transcription-PCR (RT-PCR) of three
      genomic regions. The RNA sequences were determined for 519 bases of these 17
      isolates at the putative junction between the C terminus of 3C and the N terminus
      of 3D. The analyses revealed an approximately 90% homology between these
      isolates, which were then divided into two groups: group 1 (genotype A) included
      six isolates from four outbreaks and one isolate from a traveler and group 2
      (genotype B) included one isolate from the other outbreak, four isolates from
      returning travelers, and all of the isolates from the Pakistani children. Based
      on the isolate sequences, a primer pair and a biotin-labeled probe were designed
      for amplification and detection of 223 bases at the 3C-3D junction of Aichi virus
      RNA in fecal specimens. The Aichi virus RNA was detected in 54 (55%) of 99 fecal
      specimens from the patients in 12 (32%) of 37 outbreaks of gastroenteritis in
      Japan. Of the 12 outbreaks, 11 were suspected to be due to genotype A. These
      results indicated that RT-PCR can be a useful tool to detect Aichi virus in stool
      samples and that a sequence analysis of PCR products can be employed to identify
      the prevalent strain in each incident.

PMID- 10921959
TI  - Identification of members of the Burkholderia cepacia complex by species-specific
      PCR.
AB  - Definitive identification of the species in the Burkholderia cepacia complex by
      routine clinical microbiology methods is difficult. Phenotypic tests to identify
      B. multivorans and B. vietnamiensis have been established; more recent work
      indicates B. stabilis may also be identified by growth characteristics and
      biochemical tests. However, attempts to identify genomovars I and III have, thus
      far, proved unsuccessful. Previously, we demonstrated the utility of two primer
      pairs, directed to the rRNA operon, to specifically identify the B. cepacia
      complex in a PCR. One of these primer pairs, G1-G2, only amplified a DNA fragment
      from genomovars I and III and B. stabilis in a PCR with genomic DNA isolated from
      prototypical strains representing the five genomovars. Sequence analysis of the
      rRNA operon for all the genomovars indicated that this primer pair targeted a
      region shared by these isolates. Further analysis revealed a region of
      heterogeneity between genomovar III and B. stabilis internal to the amplified
      product of G1-G2. Primers designed to target this region were tested with
      prototypical strains following an initial amplification with the G1-G2 primer
      pair. New primers specific for the prototypical genomovar III and B. stabilis
      were designated SPR3 and SPR4, respectively. Analysis of 93 isolates representing
      18 genomovar I, 13 B. multivorans, 36 genomovar III, 11 B. stabilis, and 15 B.
      vietnamiensis isolates was performed. DNA from all isolates of genomovars I and
      III and B. stabilis was amplified by G1-G2. Genomovar III isolates yielded a
      product with SPR3/G1 while B. stabilis amplified with SPR4-G1. Genomovar I
      isolates were amplified by either SPR3-G1 or SPR4-G1, but not both. B.
      multivorans yielded a product with SPR3-G1 but not G1-G2, and B. vietnamiensis
      isolates were negative in all PCRs. Thus using an algorithm with G1-G2, SPR3-G1,
      and SPR4-G1 primers in a PCR analysis, genomovar III isolates can be separated
      from B. stabilis and the identity of B. multivorans and B. vietnamiensis can be
      confirmed.

PMID- 10921960
TI  - Species identification of mycobacteria by PCR-restriction fragment length
      polymorphism of the rpoB gene.
AB  - PCR-restriction fragment length polymorphism analysis (PRA) using the novel
      region of the rpoB gene was developed for rapid and precise identification of
      mycobacteria to the species level. A total of 50 mycobacterial reference strains
      and 3 related bacterial strains were used to amplify the 360-bp region of rpoB,
      and the amplified DNAs were subsequently digested with restriction enzymes such
      as MspI and HaeIII. The results from this study clearly show that most of the
      mycobacterial species were easily differentiated at the species level by this PRA
      method. In addition, species with several subtypes, such as Mycobacterium
      gordonae, M. kansasii, M. celatum, and M. fortuitum, were also differentiated by
      this PRA method. Subsequently, an algorithm was constructed based on the results,
      and a blinded test was carried out with more than 260 clinical isolates that had
      been identified on the basis of conventional tests. Comparison of these two sets
      of results clearly indicates that this new PRA method based on the rpoB gene is
      more simple, more rapid, and more accurate than conventional procedures for
      differentiating mycobacterial species.

PMID- 10921961
TI  - Urinary hydatid antigen detection by coagglutination, a cost-effective and rapid
      test for diagnosis of cystic echinococcosis in a rural or field setting.
AB  - We describe here coagglutination (Co-A), a rapid slide agglutination test for the
      detection of hydatid antigen in the urine for the diagnosis of cystic
      echinococcosis (CE). Paired urine and serum samples were collected from 16
      patients with surgically confirmed CE, 10 patients with ultrasound-proven CE, 14
      patients with clinically diagnosed CE, 24 patients with various parasitic
      diseases other than CE, and 25 healthy control subjects. Co-A detected excreted
      hydatid antigen in the concentrated urine of 7 of 16 (43.75%) surgically
      confirmed cases, 6 of 10 (60%) ultrasound-proven cases, and 8 of 14 (57.14%)
      clinically diagnosed cases of CE. A false-positive reaction was observed with
      12.50% of control urine specimens from patients with parasitic diseases other
      than CE and 12% of urine samples from healthy controls. The circulating antigen
      was detected in the serum in 13 of 16 (81.25%) surgically confirmed cases, 6 of
      10 (60%) ultrasound-proven cases, and 13 of 14 (92.86%) clinically diagnosed
      cases of CE. False-positive reactions were observed with three sera (12.5%) from
      controls with other parasitic diseases. The low sensitivity of Co-A for detection
      of antigen in the urine of a patient whose serum was positive for the antigen is
      possibly due to low levels of antigen in the urine. Unlike the collection of
      blood for serum, which is an invasive procedure and also requires technical
      expertise and disposable syringes, urine can be collected easily and frequently
      without causing any inconvenience to the patient. Urine as a clinical specimen
      alternative to serum would be immensely useful in the diagnosis of CE,
      particularly in a rural or field setting. In such situations as well as in poorly
      equipped laboratories, Co-A has the potential to be used as a simple, rapid, and
      economical slide agglutination test for detection of urinary hydatid antigen in
      the diagnosis of CE.

PMID- 10921963
TI  - Detection of adenoviruses (AdV) in culture-negative environmental samples by PCR
      during an AdV-associated respiratory disease outbreak.
AB  - Since 1954, adenoviruses (AdV) have been recognized as an important cause of
      acute respiratory disease (ARD) among U.S. military recruits. Until recently,
      routine oral vaccination for AdV serotypes 4 and 7 eliminated epidemic AdV
      associated ARD in this population. Now that the manufacturer has ceased
      production, vaccination has ended and AdV epidemics have reappeared. As part of a
      prospective epidemiological study during the high-risk ARD season, serial samples
      were obtained from ventilation system filters and tested for AdV by culture and
      PCR. An outbreak occurred during this surveillance. Of 59 air filters, 26 (44%)
      were AdV positive only by PCR. Sequence analysis confirmed the presence of AdV
      serotype 4, the implicated outbreak serotype. The number of AdV-related
      hospitalizations was directly correlated with the proportion of filters
      containing AdV; correlation coefficients were 0.86 (Pearson) and 0.90 (Spearman's
      rho). This is the first report describing a PCR method to detect airborne AdV
      during an ARD outbreak. It suggests that this technique can detect and quantify
      AdV-associated ARD exposure and may enable further definition of environmental
      effects on AdV-associated ARD spread.

PMID- 10921962
TI  - Molecular epidemiology of an outbreak of fulminant hepatitis B.
AB  - A nosocomial outbreak of hepatitis B occurred among the inpatients of a
      hematology unit. Nine of the 11 infected patients died from fulminant hepatitis.
      An investigation was conducted to identify the source of infection and the route
      of transmission. Two clusters of nosocomial hepatitis B were identified. The
      hepatitis B virus (HBV) genome from serum samples of all case patients, of one
      HBsAg-positive patient with acute reactivation of the infection, and of eight
      acutely infected, unrelated cases was identified by PCR amplification of viral
      DNA and was entirely sequenced. Transmission was probably associated with breaks
      in infection control practices, which occurred as single events from common
      sources or through a patient-to-patient route, likely the result of shared
      medications or supplies. Sequence analysis evidenced close homology among the
      strains from the case patients and that from the patient with reactivation, who
      was the likely source of infection. Molecular analysis of viral isolates
      evidenced an accumulation of mutations in the core promoter/precore region, as
      well as several nucleotide substitutions throughout the genome. The sequences of
      all patients were compared with published sequences from fulminant and
      nonfulminant HBV infections.

PMID- 10921964
TI  - Outbreak of methicillin-resistant Staphylococcus aureus with reduced
      susceptibility to glycopeptides in a Parisian hospital.
AB  - Epidemiological relationships were investigated between 40 methicillin-resistant
      Staphylococcus aureus (MRSA) strains with decreased glycopeptide susceptibility
      isolated from November 1998 to March 1999 from 39 patients (17 infected and 22
      colonized patients) in nine wards of the Broussais Hospital, Paris, France.
      Reduced glycopeptide susceptibility was readily detected on brain heart infusion
      (BHI) agar containing 6 microg of teicoplanin per ml and on gradient plates, but
      not by the standard disk diffusion method. The MICs of vancomycin and
      teicoplanin, determined on BHI agar, were 4 and 8 to 32 microg/ml, respectively
      (standard antibiotic dilution), and 4 to 8 and 8 to 32 microg/ml, respectively (E
      test). All strains were resistant to macrolides, aminoglycosides, tetracycline,
      rifampin, sulfonamides, and pefloxacin, showed reduced susceptibility to fusidic
      acid and fosfomycin, and were susceptible to trimethoprim and chloramphenicol.
      Pulsed-field gel electrophoresis and lysotyping revealed that a multidrug
      resistant MRSA clone with decreased susceptibility to glycopeptides has been
      discretely endemic since at least 1996 in our institution, where it was
      responsible for an outbreak in November and December 1998.

PMID- 10921965
TI  - Molecular analysis of H antigens reveals that human diarrheagenic Escherichia
      coli O26 strains that carry the eae gene belong to the H11 clonal complex.
AB  - Fifty-seven Escherichia coli O26 strains isolated from patients in six countries
      were investigated by PCR restriction fragment length polymorphism (RFLP) analysis
      of the flagellin-encoding (fliC) gene (fliC RFLP analysis). The strains were
      determined by serotyping to belong to five different H types or were nonmotile.
      The fliC RFLP analysis revealed only two different patterns among the 57 strains.
      One fliC RFLP pattern was displayed by 54 strains and was identical to that of E.
      coli H11 reference strain Su4321-41. The other fliC RFLP pattern was observed for
      three strains and was identical to that for E. coli H32 reference strain K10. The
      54 strains with the H11 fliC RFLP pattern included 22 strains of serotype
      O26:H11, 23 nonmotile strains, and 9 strains that were initially serotyped as H2,
      H8, H21, and H32 but that were confirmed to express H11 by repeat serotyping. All
      54 strains with the H11 fliC RFLP pattern contained the attaching-and-effacing
      (eae) gene. The three strains with the H32 fliC RFLP pattern belonged to serotype
      O26:H32, and all were eae negative. The fliC genes of 14 selected E. coli O26:H11
      strains isolated between 1964 and 1999 had identical nucleotide sequences. Our
      results demonstrate that E. coli O26 strains that carry the eae gene belong
      exclusively to the H11 clonal complex. Since there were no H11 fliC allelic
      variations among the O26 strains tested, E. coli O26:H11 may have emerged
      recently. The fliC PCR-RFLP test is a reliable, easy-to-perform, and rapid method
      for determination of the H types of E. coli O26 isolates.

PMID- 10921966
TI  - Comparison of BACTEC MYCO/F LYTIC and WAMPOLE ISOLATOR 10 (lysis-centrifugation)
      systems for detection of bacteremia, mycobacteremia, and fungemia in a developing
      country.
AB  - In less-developed countries, studies of bloodstream infections (BSI) have been
      hindered because of the difficulty and costs of culturing blood for bacteria,
      mycobacteria, and fungi. During two study periods (study period I [1997] and
      study period II [1998]), we cultured blood from patients in Malawi by using the
      BACTEC MYCO/F LYTIC (MFL), ISOLATOR 10 (Isolator), Septi-Chek AFB (SC-AFB), and
      Septi-Chek bacterial (SC-B) systems. During study period I, blood was inoculated
      at 5 ml into an MFL bottle, 10 ml into an Isolator tube for lysis and
      centrifugation, and 10 ml into an SC-B bottle. Next, 0.5-ml aliquots of Isolator
      concentrate were inoculated into an SC-AFB bottle and onto Middlebrook 7H11 agar
      slants, chocolate agar slants, and Inhibitory Mold Agar (IMA) slants. During
      study period II, the SC-B and chocolate agar cultures were discontinued. MFL
      growth was detected by fluorescence caused by shining UV light (lambda = 365 nm)
      onto the indicator on the bottom of the bottle. During study period I, 251 blood
      cultures yielded 44 bacterial isolates. For bacteremia, the MFL was similar to
      the Isolator concentrate on chocolate agar (34 of 44 versus 27 of 44; P, not
      significant [NS]), but more sensitive than the SC-B bottle (34 of 44 versus 24 of
      44; P = 0.05). For both study periods combined, 486 blood cultures yielded 37
      mycobacterial and 13 fungal isolates. For mycobacteremia, the sensitivities of
      the MFL and Isolator concentrate in the SC-AFB bottle were similar (30 of 37
      versus 29 of 37; P, NS); the MFL bottle was more sensitive than the concentrate
      on Middlebrook agar (30 of 37 versus 15 of 37; P = 0.002). For fungemia, the MFL
      bottle was as sensitive as the SC-B bottle or Isolator concentrate on chocolate
      agar or IMA slants. We conclude that the MFL bottle, inoculated with just 5 ml of
      blood and examined under UV light, provides a sensitive and uncomplicated method
      for comprehensive detection of BSI in less-developed countries.

PMID- 10921967
TI  - Genetic and serologic evaluation of capsule production by bovine mammary isolates
      of Staphylococcus aureus and other Staphylococcus spp. from Europe and the United
      States.
AB  - Bovine mastitis caused by Staphylococcus aureus is responsible for major economic
      losses to the dairy industry, and more-effective therapeutic or preventive
      approaches are sorely needed. The predominance of staphylococcal capsular
      polysaccharide types 5 and 8 among human isolates from many sources is well
      documented, but there seems to be a greater variation in the distribution of
      capsular serotypes among isolates from cows. A total of 636 isolates of S. aureus
      from cases of bovine mastitis in Sweden, Denmark, Finland, Iceland, Ireland, and
      the United States were investigated for production of capsular polysaccharide
      types 5 and 8. Approximately half of all the European isolates tested were of
      serotype 8, although variation among countries and among isolates of clinical and
      subclinical origin was observed. Sweden had the highest frequency (87%) of
      serotypeable isolates, and Finland had the lowest (48%). Capsule types 5 and 8
      accounted for only 42% of the U.S. isolates tested. A few isolates showed weak
      reactivity with CP5 antiserum in a colony blot assay, and an enzyme-linked
      immunosorbent assay inhibition method confirmed that the levels of capsule
      produced by these strains were <10% of those produced by control strains. Fifty
      isolates that failed to react with capsular antisera all possessed the genes for
      production of capsular polysaccharide type 5 or 8. These results underscore the
      variability in capsule production by bovine isolates of S. aureus from different
      geographic regions. This information is important for the rational design of a
      capsule-based vaccine to prevent S. aureus bovine mastitis.

PMID- 10921968
TI  - Molecular epidemiology of metronidazole resistance in a population of Trichomonas
      vaginalis clinical isolates.
AB  - Trichomonas vaginalis, the causative agent for human trichomoniasis, is a
      problematic sexually transmitted disease mainly in women, where it may be
      asymptomatic or cause severe vaginitis and cervicitis. Despite its high
      prevalence, the genetic variability and drug resistance characteristics of this
      organism are poorly understood. To address these issues, genetic analyses were
      performed on 109 clinical isolates using three approaches. First, two internal
      transcribed spacer (ITS) regions flanking the 5.8S subunit of the ribosomal DNA
      gene were sequenced. The only variation was a point mutation at nucleotide
      position 66 of the ITS1 region found in 16 isolates (14.7%). Second, the presence
      of a 5.5-kb double-stranded RNA T. vaginalis virus (TVV) was assessed. TVV was
      detected in 55 isolates (50%). Finally, a phylogenetic analysis was performed
      based on random amplified polymorphic DNA data. The resulting phylogeny indicated
      at least two distinct lineages that correlate with the presence of TVV. A band
      sharing index indicating relatedness was created for different groups of
      isolates. It demonstrated that isolates harboring the virus are significantly
      more closely related to each other than to the rest of the population, and it
      indicated a high level of relatedness among isolates with in vitro metronidazole
      resistance. This finding is consistent with the hypothesis that drug resistance
      to T. vaginalis resulted from a single or very few mutational events. Permutation
      tests and nonparametric analyses showed associations between metronidazole
      resistance and phylogeny, the ITS mutation, and TVV presence. These results
      suggest the existence of genetic markers with clinical implications for T.
      vaginalis infections.

PMID- 10921969
TI  - Differentiation of pathogenic Bartonella species by infrequent restriction site
      PCR.
AB  - Infrequent restriction site PCR (IRS-PCR) is a recently described DNA
      fingerprinting technique based on selective amplification of restriction
      endonuclease-cleaved fragments. Bartonella isolates associated with human disease
      and related nonhuman isolates were analyzed by IRS-PCR genomic fingerprinting.
      Preparation of DNA templates began with double digestion using three different
      restriction endonuclease combinations. Combinations included the frequently
      cutting endonuclease HhaI in conjunction with an infrequently cutting
      endonuclease, EagI, SmaI, or XbaI. Digestion was followed by ligation of
      oligonucleotide adapters designed with ends complementary to the restriction
      endonuclease sites. Amplification of fragments flanked with an EagI, SmaI, or
      XbaI site in combination with an HhaI site produced a series of different-sized
      amplicons resolvable into patterns by polyacrylamide gel electrophoresis (PAGE).
      The pattern complexity was varied by the addition of selective nucleotides to the
      3' ends of the EagI-, SmaI-, or XbaI-specific primers. Amplicons were also
      generated with fluorescently labeled primers and were subsequently resolved and
      detected by capillary electrophoresis. Analysis by traditional slab PAGE and
      capillary electrophoresis provided suitable resolution of patterns produced with
      the enzyme combinations EagI-HhaI and SmaI-HhaI. However, the combination of XbaI
      HhaI produced too many fragments for sufficient resolution by traditional PAGE,
      thus requiring the better resolving properties of capillary electrophoresis. Due
      to the flexibility in modulating the pattern complexity and electrophoresis
      methods, these techniques allow for a high level of experimental optimization.
      The results provide evidence of the discriminatory power, ease of use, and
      flexibility of the IRS-PCR method as it applies to the identification of human
      pathogenic Bartonella species.

PMID- 10921970
TI  - Simple and rapid detection of Candida albicans DNA in serum by PCR for diagnosis
      of invasive candidiasis.
AB  - A rapid and sensitive PCR assay for the detection of Candida albicans DNA in
      serum was established. DNA from human serum samples was purified using the QIAamp
      blood kit, which proved to be a fast and simple method for isolating minute
      amounts of Candida DNA from clinical specimens for diagnosis of invasive
      candidiasis. Universal primer sequences used in the PCR assay are derived from
      the internal transcribed spacer rRNA gene of fungi, whereas the biotinylated
      hybridization probe used in a DNA enzyme immunoassay (DEIA) binds specifically to
      C. albicans DNA. The sensitivity of this PCR-DEIA method is very high; the
      detection limit for genomic Candida DNA is one C. albicans genome per assay.
      Blood from uninfected and infected persons, ranging from healthy volunteers,
      patients with mucocutaneous infections, and patients at risk to develop a
      systemic Candida infection to patients with an established systemic candidiasis,
      was analyzed for the presence of C. albicans to diagnose fungal infection.
      Candida DNA could not be detected in sera of 16 culture-negative controls and
      from 11 nonsystemic candidal infections by PCR or DEIA. Blood cultures from
      patients at risk were all negative for Candida, whereas all blood cultures from
      systemic candidiasis patients were positive. However, Candida DNA could be
      detected by PCR and DEIA in the serum from three out of nine patients who were at
      risk for a systemic infection and in the serum of all seven patients who had
      already developed an invasive Candida infection. PCR is more sensitive than blood
      culture, since some of the patients at risk for invasive yeast infection, whose
      blood cultures were all negative for Candida, tested positive in the PCR
      amplification. These results indicate the potential value of PCR for detecting C.
      albicans in serum samples and for identifying patients at risk for invasive
      candidiasis.

PMID- 10921971
TI  - Comparative evaluation of three human immunodeficiency virus genotyping systems:
      the HIV-GenotypR method, the HIV PRT GeneChip assay, and the HIV-1 RT line probe
      assay.
AB  - Evaluation of drug resistance by human immunodeficiency virus (HIV) genotyping
      has proven to be useful for the selection of drug combinations with maximum
      antiretroviral activity. We compared three genotyping methods for identification
      of mutations known to confer drug resistance in the reverse transcriptase (RT)
      and protease genes of HIV type 1 (HIV-1). The HIV-GenotypR method (GenotypR;
      Specialty Laboratories, Inc., Santa Monica, Calif.) with the ABI 377 DNA
      sequencer (Applied Biosystems Inc.), the HIV PRT GeneChip assay (GeneChip;
      Affymetrix, Santa Clara, Calif.), and the HIV-1 RT Line Probe Assay (LiPA;
      Innogenetics, Alpharetta, Ga.) were used to genotype plasma samples from HIV
      infected patients attending the University of Wisconsin Hospitals and Clinics and
      the Mayo Clinic. At the time of analysis, patients were failing combination
      therapy (n = 18) or were treatment naive (n = 6). Forty codons of the RT and
      protease genes were analyzed by GenotypR and GeneChip for resistance-associated
      mutations. LiPA analyzed seven RT codons for mutations. Each sample was genotyped
      by all three assays, and each assay was subjected to pairwise comparisons. At
      least 92% of the codons tested (by the three assays) in paired comparisons were
      concordant. GenotypR and GeneChip demonstrated 96.6% concordance over the 40
      codons tested. GenotypR identified slightly more mutations than GeneChip and
      LiPA; GeneChip identified all primary mutations that corresponded to failing
      treatment regimens. Each assay identified at least 84% of the mutations
      identified by the other assays. Mutations that were discordant between the assays
      mainly comprised secondary mutations and natural polymorphisms. The assays had
      better concordance for mutations that corresponded to current failing regimens,
      present in the more predominant viral quasispecies. In the treatment-naive
      patients, GenotypR, GeneChip, and LiPA mainly identified wild-type virus. Only
      the LiPA identified K70R, a possible transmitted zidovudine resistance mutation,
      in the RT gene of a treatment-naive patient. We conclude that although
      discrepancies in results exist between assays, each assay showed a similar
      capacity to identify potentially clinically relevant mutations related to patient
      treatment regimens.

PMID- 10921973
TI  - Clinical significance and antibiotic resistance patterns of Leminorella spp., an
      emerging nosocomial pathogen.
AB  - Although Leminorella spp., members of the family Enterobacteriaceae, were
      previously isolated from feces and urine specimens, clinical correlates have not
      been studied. We conducted a retrospective study to investigate the clinical
      significance and disease spectrum of these organisms, as well as their antibiotic
      susceptibility patterns. Identification and susceptibility testing were performed
      by an automated system. Eighteen cases were identified retrospectively during a
      28-month period (1/97 to 4/99), representing an incidence of 11 cases per 100,000
      patient admissions. The medical records of 14 patients were reviewed. The average
      patient age was 67 years, and 78% were males. Patients had multiple and diverse
      underlying conditions which might have predisposed them to infection. Leminorella
      spp. were classified as definite pathogens in 43% of the cases, probable
      pathogens in 29%, and possible pathogens in 21%. In one case of asymptomatic
      bacteriuria, the isolate had no clinical significance. All infections but one
      were nosocomial. Clinical syndromes included urinary tract infection in six
      patients, surgical site infection in three patients, and primary bacteremia,
      peritonitis, respiratory tract infection, and soft tissue infection in one
      patient each. Isolates were uniformly susceptible to imipenem. Other beta-lactam
      agents had poor activity against the isolates. We conclude that Leminorella spp.
      are significant nosocomial pathogens that are capable of causing a variety of
      clinical syndromes and are resistant to multiple antibiotic agents.

PMID- 10921972
TI  - Genetic diversity, distribution, and serological features of hantavirus infection
      in five countries in South America.
AB  - Since 1995 when the first case of hantavirus pulmonary syndrome (HPS) was
      reported in Patagonia, there have been more than 400 cases of HPS reported in
      five countries in South America. The first case of HPS was associated with Andes
      (AND) virus. In this study, we report on the genetic diversity, geographical
      distribution, and serological features of hantavirus infection in six countries
      in South America based on 87 HPS cases from Argentina, Bolivia, Chile, Paraguay,
      and Uruguay. An early immunoglobulin M (IgM), IgA, and IgG humoral response was
      observed in almost all HPS cases. The IgM response appears to peak 1 or 2 days
      after the onset of symptoms. Peak IgG antibody titers occur mostly after the
      first week. Low IgG titers or the absence of IgG was associated with higher
      mortality rates. The IgA response peaks around day 15 and then rapidly decreases.
      The results of phylogenetic analysis based on partial M-fragment G1- and G2
      encoding sequences showed that HPS cases from the five countries were infected
      with viruses related to AND or Laguna Negra (LN) virus. Within AND virus-infected
      persons, at least five major genetic lineages were found; one lineage was
      detected in Uruguayan and Argentinean cases from both sides of the Rio de la
      Plata river. Two Paraguayan patients were infected with a virus different from LN
      virus. According to the results of phylogenetic analyses, this virus probably
      belongs to a distinct lineage related more closely to the AND virus than to the
      LN virus, suggesting that there is probably an Oligoryzomys-borne viral variant
      circulating in Paraguay. These studies may contribute to a better understanding
      of hantavirus human infection in South America.

PMID- 10921974
TI  - Urine D-arabinitol/L-arabinitol ratio in diagnosis of invasive candidiasis in
      newborn infants.
AB  - Infants treated in neonatal intensive care units suffer an increased risk for
      invasive candidiasis, but the diagnosis is sometimes difficult. D-arabinitol is a
      metabolite of most pathogenic Candida species. An elevated urine D-arabinitol/L
      arabinitol (DA/LA) ratio is a sensitive sign of invasive candidiasis in children
      with cancer, but the method has not been previously evaluated for newborn
      infants. We therefore enrolled 117 infants in a neonatal intensive care unit, and
      411 urine samples were obtained on filter paper. The DA/LA ratio was measured by
      gas chromatography-mass spectrometry. For 81 infants with no suspicion of
      superficial or invasive candidiasis, the urine DA/LA ratio was 2.7 +/- 0.7 (mean
      +/- standard deviation [SD]). The upper cutoff level was set at 4.8 (mean plus 3
      SD). Of 22 infants with mucocutaneous candidiasis and not given systemic
      antifungal treatment, two had elevated DA/LA ratios, which normalized after
      removal of intravascular catheters. Eight other infants were given empiric
      antifungal treatment but had negative cultures; five of these had repeatedly
      elevated DA/LA ratios. Six infants with culture-positive invasive candidiasis all
      had one or more samples with elevated ratios. For seven infants, three with
      suspected and four with confirmed invasive candidiasis (for which follow-up
      samples were available), ratios normalized during antifungal treatment. In
      conclusion, urine DA/LA ratio determination is a rapid test and can be used for
      newborns. It is possibly more sensitive than fungal blood cultures in the
      diagnosis of invasive candidiasis and can also be used for monitoring the effect
      of antifungal treatment.

PMID- 10921975
TI  - Molecular identification of Dialister pneumosintes in subgingival plaque of
      humans.
AB  - Dialister pneumosintes is a nonfermentative, anaerobic, gram-negative rod that
      grows with small, circular, transparent, shiny, smooth colonies on blood agar.
      Even though D. pneumosintes has been recovered from deep periodontal pockets,
      little is known about the relationship between the organism and destructive
      periodontal disease. This study describes a rapid PCR method to identify D.
      pneumosintes in periodontal samples. The PCR identification method detected as
      little as 10 pg of D. pneumosintes DNA or about 1 to 10 cells without nonspecific
      amplification of various periodontopathic bacteria. Twelve of 22 subgingival
      samples from adult periodontitis lesions yielded D. pneumosintes either by
      culture or by PCR identification. In culture-positive samples, D. pneumosintes
      averaged 3.9% (0.001 to 10.8%) of total isolates. Studies are needed to delineate
      virulence factors of D. pneumosintes pertinent to periodontal disease.

PMID- 10921976
TI  - Duplex PCR for differential identification of Mycobacterium bovis, M. avium, and
      M. avium subsp. paratuberculosis in formalin- fixed paraffin-embedded tissues
      from cattle.
AB  - We previously isolated and sequenced two genomic segments of Mycobacterium avium
      subsp. paratuberculosis, namely, f57, a species-specific sequence, and the p34
      gene, coding for a 34-kDa antigenic protein. Comparison of sequences upstream of
      the p34 open reading frame (us-p34) from M. avium subsp. paratuberculosis and M.
      tuberculosis showed a 79-base deletion in M. tuberculosis. Sequence analysis of
      the p34 genes in another two species, M. bovis (strain BCG) and M. avium (strain
      D4), confirmed the differences observed between tuberculous and nontuberculous
      species. A duplex diagnostic PCR strategy based on coamplification of
      nonhomologous us-p34 and species-specific f57 sequences was therefore developed.
      Duplex PCR yielded three different patterns, specific either for tuberculous
      bacilli (M. tuberculosis, M. bovis, and M. africanum), for both nontuberculous
      mycobacteria M. avium and M. intracellulare, or for M. avium subsp.
      paratuberculosis. The specificity of this single-step DNA-based assay was
      assessed on DNA from cultured mycobacterial strains, as well as on a panel of
      formalin-fixed and paraffin-embedded tissues from cattle. Molecular assay results
      from tissular DNA were compared to conventional bacteriological and histological
      test results, including those obtained by Ziehl-Neelsen staining on tissue biopsy
      specimens. Molecular discrimination was successful and confirmed the value of
      duplex us-p34 and f57 sequence amplification for differential diagnosis of
      tuberculosis, paratuberculosis, or infections caused by other members of the M.
      avium complex.

PMID- 10921977
TI  - Fluorescence-based quantitative methods for detecting human immunodeficiency
      virus type 1-induced syncytia.
AB  - Cell fusion induced by human immunodeficiency virus type 1 (HIV-1) is usually
      assessed by counting multinucleated giant cells (syncytia) visualized by light
      microscopy. Currently used methods do not allow quantification of syncytia, nor
      do they estimate the number of cells involved in cell fusion. We describe two
      fluorescence-based methods for the detection and quantification of HIV-1-induced
      in vitro syncytium formation. The lymphoblastoid cell lines MT-2 and SupT1 were
      infected with syncytium-inducing (SI) HIV-1 isolates. Syncytia were detected by
      DNA staining with propidium iodide using flow cytometry to determine cell size or
      by two-color cytoplasmic staining of infected cell populations by using
      fluorescence microscopy. Both methods were able to detect and quantify HIV
      induced syncytia. The methods could distinguish between SI and non-SI HIV
      isolates and could be used with at least two separate types of CD4(+) T-cell
      lines. Small syncytia can be readily identified by the two-color cytoplasmic
      staining method. Both methods were also shown to be useful for evaluating
      antiretroviral compounds, as demonstrated by the accurate assessment of HIV
      inhibition by azidothymidine (zidovudine), dideoxycytidine (zalcytibine), and
      hydroxyurea. These fluorescence-based assays allow a rapid and practical method
      for measuring HIV replication and anti-HIV activity of potential inhibitory
      compounds.

PMID- 10921979
TI  - High-resolution genotyping of Chlamydia trachomatis from recurrent urogenital
      infections.
AB  - A method for Chlamydia trachomatis restriction fragment length polymorphism
      (RFLP) analysis and complete sequencing of omp1 was developed for use on samples
      collected at home, and results were compared. Genotyping by sequencing was
      superior to RFLP analysis. The omp1 gene in 31 clinical strains harbored few
      mutations compared to the same gene in ATCC reference strains. Follow-up samples
      obtained during a 24-week period from 31 patients showed recurrence with the same
      genotype in five cases and a new genotype in one case.

PMID- 10921978
TI  - Diagnostic utility of a multiplex herpesvirus PCR assay performed with
      cerebrospinal fluid from human immunodeficiency virus-infected patients with
      neurological disorders.
AB  - We used a multiplex nested-PCR assay for the simultaneous detection in
      cerebrospinal fluid (CSF) of five human herpesviruses (HVs) (cytomegalovirus
      [CMV], Epstein-Barr virus [EBV], varicella-zoster virus [VZV], herpes simplex
      virus [HSV], and human herpesvirus 6 [HHV-6]) in a clinical evaluation of human
      immunodeficiency virus (HIV)-infected patients with neurological disorders. This
      method, which has the advantages of being rapid and economical, would be of
      particular interest for the diagnosis of neurological syndromes caused by more
      than one HV. We studied 251 CSF samples from 219 patients. HV DNA was
      demonstrated in 93 (37%) of the CSF samples (34% of the patients). CMV was the HV
      most frequently detected in our patients (25%), while EBV, VZV, HSV, and HHV-6
      DNAs were present in significantly fewer cases (7, 4, 3, and 1%, respectively).
      When results were compared with the final etiological diagnoses of the patients,
      the multiplex HV PCR showed high specificity for the diagnosis of CMV and VZV
      neurological diseases and for cerebral lymphoma (0.95, 0.97, and 0.99,
      respectively). The sensitivity of the assay was high for CMV disease (0.87), was
      low for cerebral lymphoma (0.33), and was not evaluable for VZV disease due to
      the small number of patients with this diagnosis. Nevertheless, detection of VZV
      DNA had possible diagnostic value in four of the nine cases, and EBV DNA
      amplification always predicted the diagnosis of cerebral lymphoma in patients
      with cerebral masses. Detection of HSV DNA was frequently associated with CMV
      amplification and fatal encephalitis. HHV-6 was not considered to have a
      pathogenetic role in the three cases in which it was detected. This multiplex HV
      PCR assay is a specific and clinically useful method for the evaluation of HIV
      infected patients with neurological disorders related to HV.

PMID- 10921980
TI  - Genetic characterization of toxin A-negative, toxin B-positive Clostridium
      difficile isolates by PCR.
AB  - Toxin-specific enzyme immunoassays, cytotoxicity assays, and PCR were used to
      analyze 48 toxin A-negative, toxin B-positive Clostridium difficile isolates from
      various geographical sites around the world. All the isolates were negative by
      the TOX-A TEST and positive by the TOX A/B TEST. A deletion of approximately 1.7
      kb was found at the 3' end of the toxA gene for all the isolates, similar to the
      deletion in toxinotype VIII strains (e.g., C. difficile serotype F 1470).
      Additional PCR analysis indicated that the toxin B encoded by these isolates
      contains sequence variations downstream of the active site compared to the
      sequence of reference strain VPI 10463. This variation may extend the
      glucosylation spectrum to Ras proteins, as observed previously for closely
      related lethal toxin from Clostridium sordellii and toxin B from toxin A
      negative, toxin B-positive strain F 1470. Toxin A-negative, toxin B-positive
      isolates have recently been associated with disease in humans, and they may be
      more common than was previously supposed.

PMID- 10921981
TI  - Rapid detection of Campylobacter jejuni in stool specimens by an enzyme
      immunoassay and surveillance for Campylobacter upsaliensis in the greater Salt
      Lake City area.
AB  - The Alexon-Trend, Inc. (Ramsey, Minn.), ProSpecT Campylobacter microplate assay
      was compared with culture on a Campy-CVA plate (Remel, Lenexa, Kans.) and blood
      free campylobacter agar with cefoperazone (20 microg/ml), amphotericin B (10
      microg/ml), and teicoplanin (4 microg/ml) (CAT medium; Oxoid Limited, Hampshire,
      England) with 631 patient stool samples. The CAT medium was used to isolate
      Campylobacter upsaliensis. The enzyme immunoassay (EIA) had a sensitivity and a
      specificity of 89 and 99%, respectively, and the positive and negative predictive
      values were 80 and 99%, respectively. Even though we extensively looked for C.
      upsaliensis in stool samples from patients from the greater Salt Lake City area,
      we did not isolate this species during the study period. The overall excellent
      specificity of the EIA allows rapid detection and treatment of positive patients;
      however, a negative result should be confirmed by culture when clinical suspicion
      is high.

PMID- 10921983
TI  - Validation of the abbreviated Brucella AMOS PCR as a rapid screening method for
      differentiation of Brucella abortus field strain isolates and the vaccine
      strains, 19 and RB51.
AB  - The Brucella AMOS PCR assay was previously developed to identify and
      differentiate specific Brucella species. In this study, an abbreviated Brucella
      AMOS PCR test was evaluated to determine its accuracy in differentiating Brucella
      abortus into three categories: field strains, vaccine strain 19 (S19), and
      vaccine strain RB51/parent strain 2308 (S2308). Two hundred thirty-one isolates
      were identified and tested by the conventional biochemical tests and Brucella
      AMOS PCR. This included 120 isolates identified as B. abortus S19, 9 identified
      as B. abortus strain RB51, 57 identified as B. abortus biovar 1, 15 identified as
      B. abortus bv. 2, 1 identified as B. abortus bv. 2 (M antigen dominant), 7
      identified as B. abortus bv. 4, and 22 identified as B. abortus S2308 and
      isolated from experimentally infected cattle. The Brucella AMOS PCR correctly
      identified each isolate as RB51/S2308, S19, or a field strain of Brucella.

PMID- 10921982
TI  - A molecular epidemiological study of Mycobacterium simiae isolated from AIDS
      patients in Guadeloupe.
AB  - A molecular epidemiological study of Mycobacterium simiae strains isolated from
      AIDS patients in Guadeloupe was performed by the random amplification of
      polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE) of DraI- or
      XbaI-digested bacterial DNAs. A comparison of RAPD profiles suggested a
      similarity of banding patterns within a group of patients (two clusters of two
      and three patients), but the available epidemiological and clinical information
      did not support this finding. PFGE, on the other hand, showed that all the
      patients were contaminated with individual isolates. Combined numerical analysis
      performed by compiling the PFGE patterns obtained after XbaI and DraI digestions
      of bacterial DNAs suggested the occurrence of polyclonal infection in three of
      nine patients. Our results do not support a common source of M. simiae infection
      in Guadeloupe.

PMID- 10921984
TI  - Borna disease in a free-ranging lynx (Lynx lynx).
AB  - A free-ranging lynx (Lynx lynx) was shot because of its abnormal behavior.
      Histopathological examination revealed a nonsuppurative meningoencephalitis. In
      situ hybridization, immunohistochemistry, and reverse transcriptase PCR analysis
      showed the presence of Borna disease virus infection in the brain. To our
      knowledge, this is the first confirmed case of Borna disease in a large felid.

PMID- 10921985
TI  - Simple and reliable multiplex PCR assay for surveillance isolates of vancomycin
      resistant enterococci.
AB  - Conditions have been optimized for the use of a multiplex PCR for the detection
      of vancomycin-resistant enterococci in nosocomial surveillance specimens. Seven
      primer sets targeting the genes vanA, vanB, vanC1, vanC2/C3 Enterococcus faecalis
      specific, Enterococcus faecium-specific, and rrs (16S rRNA) were used in one
      reaction tube. The PCR method developed in the present study is simple and
      reliable for the rapid characterization of vancomycin-resistant enterococci.

PMID- 10921986
TI  - Use of 5-bromo-4-chloro-3-indolyl-alpha-D-N-acetylneuraminic acid in a novel spot
      test To identify sialidase activity in vaginal swabs from women with bacterial
      vaginosis.
AB  - The validity of measuring vaginal sialidase activity to identify bacterial
      vaginosis (BV) was determined by using 5-bromo-4-chloro-3-indolyl-alpha-D-N
      acetylneuraminic acid in a near-patient test. The sensitivity and specificity of
      the test for prediction of BV were 95.6 and 96.3%, respectively. Positive and
      negative predictive values were 95.6 and 96.3%, respectively. This test may be an
      alternative to Gram staining.

PMID- 10921987
TI  - Detection of rabies virus antigen in dog saliva using a latex agglutination test.
AB  - Dog bites are responsible for more than 90% of human rabies deaths in Asia. We
      developed a simple and inexpensive test based on latex agglutination (LA) for
      rabies virus antigen detection in dog saliva. Rabies virus antigen could be
      detected by agglutination on a glass slide using latex particles coated with
      gamma globulin. By evaluation of paired saliva-brain specimens from 238 dogs, the
      LA test using saliva was 99% specific and 95% sensitive compared to the
      fluorescent antibody test (FAT) on brain smears. The advantages of the LA test
      over the standard FAT are that it is comparatively simple and there is no need to
      kill the animal before examination.

PMID- 10921989
TI  - Borrelia isolates in Northern Colorado identified as Borrelia bissettii.
AB  - Previous work described Borrelia burgdorferi sensu lato group DN127 as a new
      genospecies, Borrelia bissettii, and prompted the present study to identify the
      Borrelia spp. that exist in northern Colorado. To determine the genospecies
      present, we analyzed two specific intergenic spacer regions located between the
      5S and 23S and the 16S and 23S ribosomal genes. Phylogenetic analysis of the
      derived sequences clearly demonstrated that these isolates, originating from
      rodents captured in the foothills of northern Colorado, diverged from B.
      burgdorferi sensu stricto by 5 to 5.5% and were members of the new genospecies B.
      bissettii.

PMID- 10921988
TI  - Lactoferrin and eosinophilic cationic protein in nasal secretions of patients
      with experimental rhinovirus colds, natural colds, and presumed acute community
      acquired bacterial sinusitis.
AB  - To distinguish sinusitis from uncomplicated "colds," we examined lactoferrin and
      eosinophilic cationic protein (ECP) in nasal secretions. Lactoferrin titers were
      >/=1:400 in 4% of persons with uncomplicated colds and controls but in 79% of
      persons with sinusitis or purulent sputa. ECP levels were >200 ng/ml in 61% of
      persons with colds and >3,000 ng/ml in 62% of persons with sinusitis. Nasal
      lactoferrin helps distinguish sinusitis from colds.

PMID- 10921990
TI  - Molecular identification of Paracoccidioides brasiliensis by PCR amplification of
      ribosomal DNA.
AB  - We have amplified and sequenced the 5.8S and 28S ribosomal DNA genes and
      intergenic regions of Paracoccidioides brasiliensis, strain Pb01. Using primers
      specifically designed for both ribosomal DNA regions, we were able to
      discriminate between P. brasiliensis and other human pathogenic fungi by PCR. The
      use of this molecular marker could be important for paracoccidiodomycosis
      diagnosis and ecological and molecular epidemiological studies of P. brasiliensis
      in Latin America.

PMID- 10921991
TI  - Recovery and identification of West Nile virus from a hawk in winter.
AB  - West Nile virus was recovered from the brain of a red-tailed hawk that died in
      Westchester County, N.Y., in February 2000. Multiple foci of glial cells,
      lymphocytes, and a few pyknotic nuclei were observed in the brain. Three to 4
      days after inoculation of Vero cells with brain homogenates, cytopathic changes
      were detected. The presence of West Nile virus antigen in fixed cells or cell
      lysates was revealed by fluorescent antibody testing or enzyme-linked
      immunosorbent assay, respectively. Furthermore, Reverse transcriptase-PCR with
      primers specific for the NS3 gene of West Nile virus resulted in an amplicon of
      the expected size (470 bp). Electron microscopy of thin sections of infected Vero
      cells revealed the presence of viral particles approximately 40 nm in diameter,
      within cytoplasmic vesicles. The demonstration of infection with the West Nile
      virus in the dead of the winter, long after mosquitoes ceased to be active, is
      significant in that it testifies to the survival of the virus in the region
      beyond mosquito season and suggests another route of transmission: in this case,
      prey to predator.

PMID- 10921992
TI  - Utility of commercial systems for identification of Burkholderia cepacia complex
      from cystic fibrosis sputum culture.
AB  - Performances of several commercial test systems were reviewed to determine their
      relative levels of accuracy in identifying Burkholderia cepacia complex isolates
      recovered from cystic fibrosis sputum culture. Positive predictive values ranged
      from 71 to 98%; negative predictive values ranged from 50 to 82%. All systems
      misidentified B. cepacia complex. The species most frequently misidentified as B.
      cepacia was Burkholderia gladioli. These data support the results of previous
      studies that recommend confirmatory testing, including the use of DNA-based
      methods, for sputum culture isolates presumptively identified as B. cepacia.

PMID- 10921993
TI  - Evaluation of LightCycler PCR for implementation of laboratory diagnosis of
      herpes simplex virus infections.
AB  - Five hundred specimens (288 genital, 192 dermal, and 20 ocular) were extracted by
      technologists, and the DNA was assayed by LightCycler PCR (DNA polymerase and
      thymidine kinase [TK] gene targets) and by conventional tube and shell vial cell
      culture. One hundred fifty-eight confirmed (by cell culture and TK target PCR)
      positive and LightCycler-positive specimens were detected during the first 30 PCR
      cycles. LightCycler PCR-positive results for cycles 31 to 45 (39 of 67 [58.2%])
      required confirmation by another PCR target (TK). LightCycler PCR is more
      sensitive (n = 197; 23.1%) than cell cultures (n = 150) for the routine
      laboratory detection of herpes simplex virus infections.

PMID- 10921994
TI  - Mutations in the rpoB gene of multidrug-resistant Mycobacterium tuberculosis
      isolates from Brazil.
AB  - Mutations in a 69-bp region of the rpoB gene associated with rifampin resistance
      (Rif(r)) in 100 isolates (82 Rif(r)) from three states of Brazil were studied.
      Twenty-one different kinds of mutations were identified in the Rif(r) isolates,
      and six new alleles are described.

PMID- 10921995
TI  - Human infection with Halomonas venusta following fish bite.
AB  - Halomonas venusta, a moderately halophilic, nonfermentative gram-negative rod, is
      reported for the first time as a human pathogen in a wound that originated from a
      fish bite.

PMID- 10921996
TI  - Two successive hepatitis C virus infections in an intravenous drug user.
AB  - We report the case of an occasional intravenous drug user who developed two
      successive hepatitis C virus (HCV) infections. The first infection led to
      seroconversion (anti-HCV antibodies detected) and the detection of HCV RNA in
      serum. After a spontaneous recovery (normalization of alanine aminotransferase
      levels and HCV RNA clearance), a second HCV infection was observed, with the
      recurrence of HCV viremia. Antibody directed against HCV serotype 1 was detected
      throughout the follow-up monitoring, but two different HCV strains were
      identified during the two infectious episodes: genotype 1a for the first and
      genotype 3a for the second. This observation shows that primary HCV infection
      does not confer protective immunity against subsequent infection with viruses of
      other genotypes. This may hamper the development of a vaccine. Conflicting
      results were obtained in genotyping and serotyping assays, suggesting that the
      serotyping method cannot be used to identify the HCV type in patients, such as
      intravenous drug users, who are exposed to successive HCV infections.

PMID- 10921997
TI  - Isolation of Legionella oakridgensis from two patients with pleural effusion
      living in the same geographical area.
AB  - Two cases of Legionnaire's disease caused by Legionella oakridgensis were
      diagnosed at the university hospital in Nantes, France. The two patients'
      isolates were identified by means of phenotyping and genotyping methods.
      Epidemiological investigations concluded that the first case was hospital
      acquired while the second case was considered community acquired.

PMID- 10921998
TI  - The afferent signalling of fever.
AB  - When infectious micro-organisms invade the body, fever often ensues. It is the
      most familiar and most manifest sign of infection. Yet, despite its ubiquity,
      little is definitively known regarding the detailed mechanism of its induction.
      The generally prevalent view is that entry into the body of such infectious micro
      organisms first activates innate immune responses, which include the release of a
      complex variety of soluble mediators. Among these, the cytokines tumour necrosis
      factor (TNF) alpha, interleukin (IL)-1beta and IL-6 are thought to convey the
      pyrogenic message to the brain region where fever is regulated, namely the
      preoptic area (POA) of the anterior hypothalamus. The mechanism by which these
      peripheral signals may be transduced into central nervous signals is currently a
      matter of lively controversy. The issue is not trivial because, to the extent
      that these relatively large, hydrophilic peptides may be released into the
      circulatory system and transported to the brain by the bloodstream, they have to
      pass through the blood-brain barrier (BBB), which is impermeable to them. At
      least two routes are possible, and there is evidence for both: (1) active
      transport across the BBB by cytokine-specific carriers, and (2) message transfer
      where the BBB is 'leaky', i.e. in the 'sensory' circumventricular organs,
      particularly the organum vasculosum laminae terminalis (OVLT), on the midline of
      the POA, by the presumptive activation by, an as yet, indeterminate means of
      neurons projecting into the OVLT from the brain. But alternative pathways are
      also possible and support for some has been obtained: (1) the circulating
      cytokine-induced generation of BBB-permeable prostaglandin E2, the most proximal,
      putative mediator of fever, by endothelial cells of the cerebral microvasculature
      or perivascular microglia and meningeal macrophages, and (2) direct transmission
      to the POA of the pyrogenic messages via peripheral (largely vagal) afferent
      nerves activated by the cytokines. However, all four of these mechanisms have
      shortcomings (Blatteis & Sehic, 1997).

PMID- 10921999
TI  - Divergence in the behaviour of the dihydropyridine receptor in muscle.
AB  - The process leading from electrical membrane excitation of skeletal muscle fibres
      to contraction is a classic example of a rapid cellular activation mechanism. Its
      initial step is a massive release of Ca2+ from a storage compartment, the
      sarcoplasmic reticulum (SR), into the myoplasm. Ca2+ release occurs through
      ryanodine receptors (RyRs), homotetrameric ion channel proteins of an enormous
      mass (ca 2 3 million Da). In excitation-contraction (EC) coupling the type 1
      isoform of the RyR (RyR1) is remotely controlled by plasma membrane voltage. A
      system of narrow invaginations of the plasma membrane, the transverse tubules (T
      system), carries the muscle action potential to specialized regions, the triads,
      where the membranes of the T-system and the terminal cisternae of the SR are in
      close apposition.

PMID- 10922001
TI  - Single channel analysis of a novel NMDA channel from Xenopus oocytes expressing
      recombinant NR1a, NR2A and NR2D subunits.
AB  - Two types of subunit (an NR1 subunit and one of the NR2 subunits) are sufficient
      to form efficient NMDA receptors. In order to investigate whether functional
      receptors may contain more than one sort of NR2 subunit, NR1, NR2A and NR2D
      subunits were co-expressed in Xenopus oocytes. Single channel recordings from the
      oocytes showed, as expected, channel openings that are characteristic of NR1/NR2A
      receptors (ca 50 and 40 pS conductances), and channels characteristic of NR1/NR2D
      receptors (ca 40 and 20 pS conductances). However, they also contained a novel
      channel that contained conductances of ca 30, 40 and 50 pS, with direct
      transitions between all three levels. It is postulated that the novel channel
      contains NR1, NR2A and NR2D subunits. The implications of this for receptor
      stoichiometry are discussed. The novel channel was intermediate between the
      NR1/NR2A and NR1/NR2D 'duplet' receptors in the length of the channel
      activations, and in the probability of being open during activation. Its glycine
      sensitivity was much higher than that of NR1/NR2A, and was comparable with that
      of the other 'duplet' receptors.

PMID- 10922000
TI  - Sympathetic vasodilatation in human limbs.
AB  - This review focuses on recent developments in our understanding of active
      vasodilatation in human skin and skeletal muscle. We have attempted to place
      recent advances in their historical context and review the evolution of thinking
      on active vasodilatation in these two vascular beds. In human skin, active
      vasodilatation is well established, but the neurotransmitter responsible for the
      dilatation is unknown. In human skeletal muscle, older studies provided
      circumstantial evidence consistent with sympathetically mediated vasodilatation,
      but the evidence was never unambiguous. By contrast, recent studies on active
      vasodilatation in human skeletal muscle in conjunction with a reinterpretation of
      data from previous studies casts doubt on the existence of sympathetic
      vasodilator fibres in human skeletal muscle.

PMID- 10922002
TI  - The trapping block of NMDA receptor channels in acutely isolated rat hippocampal
      neurones.
AB  - N-methyl-D-aspartate (NMDA) receptor responses were recorded from acutely
      isolated rat hippocampal neurones using the whole-cell patch-clamp technique. A
      rapid perfusion system was used to study the voltage-dependent block of NMDA
      channels by Mg2+, amantadine (AM) and N-2-(adamantyl)-hexamethylenimine (A-7).
      Mg2+, AM and A-7-induced stationary blockade of NMDA channels increased with the
      blocker concentration but did not depend on the agonist (aspartate; Asp)
      concentration. Blockade by AM and A-7, but not Mg2+, was weakly use dependent.
      'Hooked' tail currents were observed after coapplication of Asp and Mg2+, AM or A
      7. The hooked tail current kinetics, amplitude and carried charge indicated that
      Mg2+, AM and A-7 did not prevent closure and desensitization of NMDA channels nor
      agonist dissociation. Tail currents following Asp application in the absence and
      continuous presence of Mg2+, AM or A-7 had similar kinetics. Application of
      multiple stationary and kinetic criteria to the Mg2+, AM and A-7 blockade led us
      to conclude that their effects on NMDA channels can be described in terms of a
      'trapping' model, which is fully symmetrical with respect to the blocking
      transition. In general, the apparent blocking/recovery kinetics predicted by the
      fully symmetrical trapping model differ significantly from the microscopic
      kinetics and depend on the rate of binding and unbinding of the blocker, the NMDA
      channel open probability and the rate of solution exchange.

PMID- 10922003
TI  - Malignant hyperthermia mutation Arg615Cys in the porcine ryanodine receptor
      alters voltage dependence of Ca2+ release.
AB  - Ca2+ inward current and fura-2 Ca2+ transients were simultaneously recorded in
      porcine myotubes. Myotubes from normal pigs and cells from specimens homozygous
      for the Arg615Cys (malignant hyperthermia) mutation of the skeletal muscle
      ryanodine receptor RyR1 were investigated. We addressed the question whether this
      mutation alters the voltage dependence of Ca2+ release from the sarcoplasmic
      reticulum. The time course of the total flux of Ca2+ into the myoplasm was
      estimated. Analysis showed that the largest input Ca2+ flux occurred immediately
      after depolarization. Amplitude and time course of the Ca2+ flux at large
      depolarizations were not significantly different in the Arg615Cys myotubes. Ca2+
      release from the sarcoplasmic reticulum was activated at more negative potentials
      than the L-type Ca2+ conductance. In the controls, the potentials for half
      maximal activation V 1/2 were -9.0mV and 16.5 mV, respectively. In myotubes
      expressing the Arg615Cys mutation, Ca2+ release was activated at significantly
      lower depolarizing potentials (V = -23.5 mV) than in control myotubes. In
      contrast, V of conductance activation (13.5 mV) was not significantly different
      from controls. The specific shift in the voltage dependence of Ca2+ release
      caused by this mutation can be well described by altering a voltage-independent
      reaction of the ryanodine receptor that is coupled to the voltage-dependent
      transitions of the L-type Ca2+ channel.

PMID- 10922004
TI  - Mechanisms underlying InsP3-evoked global Ca2+ signals in mouse pancreatic acinar
      cells.
AB  - In secretory epithelial cells, complex patterns of Ca2+ signals regulate
      physiological processes. How these patterns are generated is still not fully
      understood. In particular, the basis of global Ca2+ waves is not clear. We have
      studied regional differences in InsP3-evoked Ca2+ release in single mouse
      pancreatic acinar cells, using high-speed (approximately 90 frames s-1), high
      sensitivity Ca2+ imaging combined with rapid (10 ms) spot photolysis (2
      micrometer diameter) of caged InsP3. Within a single region we measured Ca2+
      response latency and rate of rise to construct an InsP3 dose-response
      relationship. Spot InsP3 liberation in the secretory pole region consistently
      elicited a dose-dependent, rapid release of Ca2+. Spot InsP3 liberation in the
      basal pole region of approximately 50% of cells elicited a similar dose-response
      relationship but with a lower apparent InsP3 affinity than in the secretory pole.
      In the other cells, basal pole InsP3 liberation did not elicit active Ca2+
      release, even at the highest stimulus intensities we employed, although these
      same cells did respond when the stimulus spot was moved to different regions. We
      conclude that in the basal pole active sites of rapid Ca2+ release have a lower
      functional affinity for InsP3 than those in the secretory pole and are spread out
      in discrete sites across the basal pole. These properties explain the propagation
      of Ca2+ waves across the basal pole that are only observed at higher stimulus
      levels.

PMID- 10922005
TI  - Membrane-delimited coupling between sigma receptors and K+ channels in rat
      neurohypophysial terminals requires neither G-protein nor ATP.
AB  - Receptor-mediated modulation of ion channels generally involves G-proteins,
      phosphorylation, or both in combination. The sigma receptor, which modulates
      voltage-gated K+ channels, is a novel protein with no homology to other receptors
      known to modulate ion channels. In the present study patch clamp and
      photolabelling techniques were used to investigate the mechanism by which sigma
      receptors modulate K+ channels in peptidergic nerve terminals. The sigma receptor
      photoprobe iodoazidococaine labelled a protein with the same molecular mass (26
      kDa) as the sigma receptor protein identified by cloning. The sigma receptor
      ligands pentazocine and SKF10047 modulated K+ channels, despite intra-terminal
      perfusion with GTP-free solutions, a G-protein inhibitor (GDPbetaS), a G-protein
      activator (GTPgammaS) or a non-hydrolysable ATP analogue (AMPPcP). Channels in
      excised outside-out patches were modulated by ligand, indicating that soluble
      cytoplasmic factors are not required. In contrast, channels within cell-attached
      patches were not modulated by ligand outside a patch, indicating that receptors
      and channels must be in close proximity for functional interactions. Channels
      expressed in oocytes without receptors were unresponsive to sigma receptor
      agonists, ruling out inhibition through a direct drug interaction with channels.
      These experiments indicate that sigma receptor-mediated signal transduction is
      membrane delimited, and requires neither G-protein activation nor protein
      phosphorylation. This novel transduction mechanism is mediated by membrane
      proteins in close proximity, possibly through direct interactions between the
      receptor and channel. This would allow for more rapid signal transduction than
      other ion channel modulation mechanisms, which in the present case of
      neurohypophysial nerve terminals would lead to the enhancement of neuropeptide
      release.

PMID- 10922006
TI  - Attenuation of length dependence of calcium activation in myofilaments of
      transgenic mouse hearts expressing slow skeletal troponin I.
AB  - We compared sarcomere length (SL) dependence of the Ca2+-force relation of
      detergent-extracted bundles of fibres dissected from the left ventricle of wild
      type (WT) and transgenic mouse hearts expressing slow skeletal troponin I (ssTnI
      TG). Fibre bundles from the hearts of the ssTnI-TG demonstrated a complete
      replacement of the cardiac troponin I (cTnI) by ssTnI. Compared to WT controls,
      ssTnI-TG fibre bundles were more sensitive to Ca2+ at both short SL (1.9 +/- 0.1
      micrometer) and long SL (2.3 +/- 0.1 micrometer). However, compared to WT
      controls, the increase in Ca2+ sensitivity (change in half-maximally activating
      free Ca2+; DeltaEC50) associated with the increase in SL was significantly
      blunted in the ssTnI-TG myofilaments. Agents that sensitize the myofilaments to
      Ca2+ by promoting the actin-myosin reaction (EMD 57033 and CGP-48506)
      significantly reduced the length-dependent DeltaEC50 for Ca2+ activation, when SL
      in WT myofilaments was increased from 1.9 to 2.3 micrometer. Exposure of
      myofilaments to calmidazolium (CDZ), which binds to cTnC and increases its
      affinity for Ca2+, sensitized force developed by WT myofilaments to Ca2+ at SL
      1.9 micrometer and desensitized the WT myofilaments at SL 2.3 micrometer. There
      were no significant effects of CDZ on ssTnI-TG myofilaments at either SL. Our
      results indicate that length-dependent Ca2+ activation is modified by specific
      changes in thin filament proteins and by agents that promote the actin-myosin
      interaction. Thus, these in vitro results provide a basis for using these models
      to test the relative significance of the length dependence of activation in situ.

PMID- 10922007
TI  - Sarcomeric Ca2+ gradients during activation of frog skeletal muscle fibres imaged
      with confocal and two-photon microscopy.
AB  - Intra-sarcomeric gradients of [Ca2+] during activation of action potential
      stimulated frog single fibres were investigated with the Ca2+ indicator fluo-3
      and confocal and two-photon microscopy. The object of these experiments was to
      look for evidence of extra-junctional Ca2+ release and examine the microscopic
      diffusion of Ca2+ within the sarcomere. By exploiting the spatial periodicity of
      sarcomeres within the fibre, we could achieve a high effective line-scanning rate
      ( approximately 8000 lines s-1), although the laser scanning microscope was
      limited to < 1000 lines s-1. At this high time resolution, the time course of
      fluorescence changes was very different at the z- and m-lines, with a significant
      delay ( approximately 1 ms; 22 C) between the rise of fluorescence at the z-line
      and the m-line. To calculate the expected fluorescence changes, we used a multi
      compartment model of Ca2+ movements in the half-sarcomere in which Ca2+ release
      was restricted to triadic junctions (located at z-lines). Optical blurring by the
      microscope was simulated to generate fluorescence signals which could be compared
      directly to experimental data. The model which reproduced our experimental
      findings most accurately included Ca2+ binding by ATP, as well as indicator
      binding to immobile sarcomeric proteins. After taking sarcomeric misregistration
      within the fibre into account, there was very good agreement between the model
      and experimental results. We conclude that there is no experimental evidence for
      Ca2+ release at locations other than at z-lines. In addition, our calculations
      support the conclusion that rapidly diffusing Ca2+ buffers (such as ATP) are
      important in shaping the Ca2+ transient and that the details of intracellular
      indicator binding need to be considered to explain correctly the time course of
      fluorescence change in the fibre.

PMID- 10922008
TI  - Sympathetic innervation alters activation of pacemaker current (If) in rat
      ventricle.
AB  - Pacemaker current (If) exists in both neonatal and adult ventricles, but
      activates at more negative voltages in the adult. This study uses whole-cell
      patch clamp to investigate the factors that may contribute to the maturational
      shift of If, comparing neonatal rat ventricular myocytes that were cultured for 4
      6 days either alone, in co-culture with sympathetic nerves, or with
      neurotransmitters chronically present in culture. If recorded from nerve-muscle
      co-cultures had a significantly more negative and shallower activation-voltage
      relation than that from control muscle cultures, which was reflected in the
      midpoint potential (V50) and slope factor (K) of activation. This effect of
      innervation was prevented by the sustained presence in the culture of the alpha1
      adrenergic antagonist prazosin (Pz) at 10(-7) M. In parallel experiments,
      myocytes treated with noradrenaline (NA) at 10(-7) M or neuropeptide Y (NPY) at
      10(-7) M during culture had the same If activation as control cells, but cells
      treated with NA and NPY together had a significantly more negative and shallower
      activation curve. Maximum conductance and reversal potential were unchanged. The
      effect of chronic exposure to NA + NPY was prevented by the sustained presence of
      either Pz or the NPY Y2 selective antagonist T4-[NPY(33-36)]4 (3.5 x 10(-7) M) in
      the culture, indicating a requirement for both alpha1-adrenergic and NPY Y2
      activation. Substituting NA with the alpha1A-adrenergic selective agonist A61603
      (5(-10) x 10(-9) M), in the presence of NPY, did not alter If, suggesting the
      involvement of alpha1B- rather than alpha1A-adrenoceptors. Further, sequential
      exposure to NPY followed by NA was effective in reproducing the action of chronic
      simultaneous exposure to these agonists, but sequential exposure to NA followed
      by NPY was ineffective. The results are consistent with past studies indicating
      that NPY affects the functional expression of the alpha1B-adrenergic cascade and
      suggest that sympathetic innervation induces a negative shift of If in ventricle
      via a combined action at alpha1B-adrenergic and NPY Y2 receptors. This effect of
      innervation probably contributes to the developmental maturation of If
      activation.

PMID- 10922010
TI  - A combined mechanical and X-ray diffraction study of stretch potentiation in
      single frog muscle fibres.
AB  - The nature of the force (T) response during and after steady lengthening has been
      investigated in tetanized single muscle fibres from Rana temporaria (4 C; 2.15
      micrometer sarcomere length) by determining both the intensity of the third order
      myosin meridional X-ray reflection (IM3) and the stiffness (e) of a selected
      population of sarcomeres within the fibre. With respect to the value at the
      isometric tetanus plateau (To), IM3 was depressed to 0.67 +/- 0.04 during steady
      lengthening at approximately 160 nm s(-1) (T approximately 1.7) and recovered to
      0.86 +/- 0.05 during the 250 ms period of after-stretch potentiation following
      the rapid decay of force at the end of lengthening (T approximately 1.3); under
      the same conditions stiffness increased to 1.25 +/- 0.02 and to 1.12 +/- 0.03,
      respectively. After subtraction of the contribution of myofilaments to the half
      sarcomere compliance, stiffness measurements indicated that (1) during
      lengthening the cross-bridge number rises to 1.8 times the original isometric
      value and the average degree of cross-bridge strain is similar to that induced by
      the force-generating process in isometric conditions (2.3 nm), and (2) after
      stretch potentiation is explained by a residual larger cross-bridge number.
      Structural data are compatible with mechanical data if the axial dispersion of
      attached heads is doubled during steady lengthening and recovers half-way towards
      the original isometric value during after-stretch potentiation.

PMID- 10922009
TI  - Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1
      and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites.
AB  - Changes in the arborization and electrical excitability of the apical dendritic
      tufts of pyramidal cells of cortical layer 5 were examined during the first 2
      months (postnatal days (P)2-56) of postnatal development in rats. Reconstructions
      of biocytin-filled neurons showed that the apical dendritic trunk was continually
      growing, becoming longer and thicker and that the distance between the tuft and
      soma increased more than 5-fold. In P2 animals, both the tuft and soma had a high
      input resistance (> 500 MOmega) and the tuft was electrotonically close to the
      soma. In contrast, the apical tuft and soma of P56 neurons had a low input
      resistance (< 50 MOmega) and they were electrotonically isolated from each other.
      Depolarizing current pulses injected into the tuft of P2 cells generated mostly
      Na+-dependent regenerative dendritic potentials of short duration ( approximately
      15 ms) while in the tuft of P56 animals, complex regenerative potentials were
      generated which had a longer duration ( approximately 55 ms) and were Na+ and
      Ca2+ dependent. In young and juvenile animals (P14-28) dendritic regenerative
      potentials could be restricted to the apical dendritic tuft whereas in adult
      animals (> P42), the complex regenerative potentials frequently occurred
      simultaneously with somatic action potentials. The main developmental change in
      layer 5 pyramidal neurons, as assayed with square pulse current injections and
      synaptic stimulations, is the progressive electrotonic isolation of the dendritic
      tuft from the soma. This change is concomitant with the appearance of complex,
      mostly Na+- and Ca2+-dependent, regenerative dendritic potentials initiated
      partly in the tuft and partly in the axon. The coupling of the dendritic tuft and
      axonal initiation zones for regenerative potentials by active dendritic Na+ and
      Ca2+ conductances enables mature layer 5 pyramidal neurons to detect selectively
      the salient distal synaptic inputs and coincident synaptic inputs arriving at
      different cortical layers.

PMID- 10922011
TI  - Vacuole formation in fatigued skeletal muscle fibres from frog and mouse: effects
      of extracellular lactate.
AB  - Isolated, living muscle fibres from either Xenopus or mouse were observed in a
      confocal microscope and t-tubules were visualized with sulforhodamine B.
      Observations were made before and after fatiguing stimulation. In addition,
      experiments were performed on fibres observed in an ordinary light microscope
      with dark-field illumination. In Xenopus fibres, recovering after fatigue, t
      tubules started to show dilatations 2-5 min post-fatigue. These swellings
      increased in size over the next 10-20 min to form vacuoles. After 2-3 h of
      recovery the appearance of the fibres was again normal and force production,
      which had been markedly depressed 10-40 min post-fatigue, was close to control.
      Vacuoles were not observed in mouse fibres, fatigued with the same protocol and
      allowed to recover. In Xenopus fibres, fatigued in normal Ringer solution and
      allowed to recover in Ringer solution with 30-50 mM L-lactate substituting for
      chloride (lactate-Ringer), the number and size of vacuoles were markedly reduced.
      Also, force recovery was significantly faster. Replacement of chloride by methyl
      sulphate or glucuronate had no effect on vacuolation. Resting Xenopus fibres
      exposed to 50 mM lactate-Ringer and transferred to normal Ringer solution
      displayed vacuoles within 5-10 min, but to a smaller extent than after fatigue.
      Vacuolation was not associated with marked force reduction. Mouse fibres,
      fatigued in 50 mM lactate-Tyrode (L-lactate substituting for chloride in Tyrode
      solution) and recovering in normal Tyrode solution, displayed vacuoles for a
      limited period post-fatigue. Vacuolation had no effect on force production. The
      results are consistent with the view that lactate, formed during fatigue, is
      transported into the t-tubules where it attracts water and causes t-tubule
      swelling and vacuolation. This vacuolation may be counteracted in vivo due to a
      gradual extracellular accumulation of lactate during fatigue.

PMID- 10922012
TI  - Effects of temperature on the wall strength and compliance of frog mesenteric
      microvessels.
AB  - In single perfused mesenteric microvessels of pithed frogs, we assessed wall
      strength from the critical pressure, PB, which has to be applied within the
      vessel in order to induce openings in the walls through which fluid and cells can
      extravasate. PB was determined in capillaries and venules of tissues at 12-20 The
      P(B) (mean +/- S.E.M.) in 22 vessels between 12 and 20 degrees C, P(B) was 92.0
      +/- 7.40 cm H2O which was significantly higher than at room temperatures
      (P<0.001). The compliance of the vessel wall was estimated using both the red
      cell method and the oil meniscus technique. There was no measurable effect of
      temperature on wall compliance. The compliance of vessels from which the cells
      had been removed by previous perfusion with detergent solutions was very similar
      to that of intact vessels between 12 and 20 degrees C and between 0 and 5 degrees
      C. The negligible effects of temperature upon compliance suggest that microvessel
      walls have to be distended to a greater extent in cold tissue before P(B) is
      reached. This, together with their rapid closure, is consistent with the
      hypothesis that pressure-induced openings in microvascular walls are dependent on
      an active response of the endothelium rather than being the result of stress
      failure of the basement membrane.

PMID- 10922013
TI  - Presynaptic control of transmission along the pathway mediating disynaptic
      reciprocal inhibition in the cat.
AB  - In cat lumbar motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs)
      evoked by stimulation of antagonist motor nerves were depressed for at least 150
      ms following conditioning stimulation of flexor (1.7-2 times threshold (T)) and
      ankle extensor (5T) nerves. The aim of the present study was to investigate the
      possibility that this depression is caused by presynaptic inhibitory mechanisms
      acting at the terminals of group I afferent fibres projecting to the Ia
      inhibitory interneurones and/or the terminals of these interneurones to the
      target motoneurones. Conditioning stimulation of flexor, but not ankle extensor,
      nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic
      potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This
      depression lasted between 200 and 700 ms and was not accompanied by a depression
      of the monosynaptic EPSPs evoked by stimulation of descending pathways. These
      results suggest that flexor, but not ankle extensor, group I afferent fibres can
      modulate sensory transmission at the synapse between Ia afferent fibres and Ia
      inhibitory interneurones. Conditioning stimulation of flexor muscle nerves,
      extensor muscle nerves and cutaneous nerves produced a long-lasting increase in
      excitability of the terminals of the Ia inhibitory interneurones. The increase in
      the excitability of the terminals was not secondary to an electrotonic spread of
      synaptic excitation at the soma. Indeed, concomitant with the excitability
      increase of the terminals there were signs of synaptic inhibition in the soma.
      The unitary IPSPs induced in target motoneurones following the spike activity of
      single Ia inhibitory interneurones were depressed by conditioning stimulation of
      muscle and cutaneous nerves. Since the conditioning stimulation also evoked
      compound IPSPs in those motoneurones, a firm conclusion as to whether unitary
      IPSP depression involved presynaptic inhibitory mechanism of the terminals of the
      interneurones could not be reached. The possibility that the changes in
      excitability of the Ia interneuronal terminals reflect the presence of a
      presynaptic inhibitory mechanism similar to that operating at the terminals of
      the afferent fibres (presynaptic inhibition) is discussed.1. In cat lumbar
      motoneurones, disynaptic inhibitory postsynaptic potentials (IPSPs) evoked by
      stimulation of antagonist motor nerves were depressed for at least 150 ms
      following conditioning stimulation of flexor (1.7-2 times threshold (T)) and
      ankle extensor (5T) nerves. The aim of the present study was to investigate the
      possibility that this depression is caused by presynaptic inhibitory mechanisms
      acting at the terminals of group I afferent fibres projecting to the Ia
      inhibitory interneurones and/or the terminals of these interneurones to the
      target motoneurones. Conditioning stimulation of flexor, but not ankle extensor,
      nerves evoked a depression of the monosynaptic Ia excitatory postsynaptic
      potentials (EPSPs) recorded intracellularly in Ia inhibitory interneurones. This
      depression lasted between 200 and 700 ms and was not accompanied by a depression
      of the monosynaptic EPSPs evoked by stimulation of descending pathways. These
      results suggest that flexor, but not ankle extensor, group I afferent fibres can
      modulate sensory transmission at the synapse between Ia afferent fibres and Ia
      inhibitory interneurones. Conditioning stimulation of flexor muscle nerves,
      extensor muscle nerves and cutaneous nerves produced a long-lasting increase in
      excitability of the terminals of the Ia inhibitory interneurones. The increase in
      the excitability of the terminals was not secondary to an electrotonic spread of
      synaptic excitation at the soma. Indeed, concomitant with the excitability
      increase of the terminals there were signs of synaptic inhibition in the soma.
      The unitary IPSPs induced in target motoneurones following the spike activity of
      single Ia inhibitory interneurones were depressed by conditioning stimulation

PMID- 10922014
TI  - Depression of group Ia monosynaptic EPSPs in cat hindlimb motoneurones during
      fictive locomotion.
AB  - The effects of fictive locomotion on monosynaptic EPSPs recorded in motoneurones
      and extracellular field potentials recorded in the ventral horn were examined
      during brainstem-evoked fictive locomotion in decerebrate cats. Composite
      homonymous and heteronymous EPSPs and field potentials were evoked by group I
      intensity (<= 2T) stimulation of ipsilateral hindlimb muscle nerves. Ninety-one
      of the 98 monosynaptic EPSPs were reduced in amplitude during locomotion (mean
      depression of the 91 was to 66 % of control values); seven increased in amplitude
      (to a mean of 121 % of control). Twenty-one of the 22 field potentials were
      depressed during locomotion (mean depression to 72 % of control). All but 14 Ia
      EPSPs were smaller during both the flexion and extension phases of locomotion
      than during control. In 35 % of the cases there was < 5 % difference between the
      amplitudes of the EPSPs evoked during the flexion and extension phases. In 27 %
      of the cases EPSPs evoked during flexion were larger than those evoked during
      extension. The remaining 38 % of EPSPs were larger during extension. There was no
      relation between either the magnitude of EPSP depression or the locomotor phase
      in which maximum EPSP depression occurred and whether an EPSP was recorded in a
      flexor or extensor motoneurone. The mean recovery time of both EPSP and field
      potential amplitudes following the end of a bout of locomotion was approximately
      2 min (range, < 10 to > 300 s). Motoneurone membrane resistance decreased during
      fictive locomotion (to a mean of 61 % of control, n = 22). Because these
      decreases were only weakly correlated to EPSP depression (r 2 = 0.31) they are
      unlikely to fully account for this depression. The depression of monosynaptic
      EPSPs and group I field potentials during locomotion is consistent with the
      hypothesis that during fictive locomotion there is a tonic presynaptic regulation
      of synaptic transmission from group Ia afferents to motoneurones and
      interneurones. Such a reduction in neurotransmitter release would decrease group
      Ia monosynaptic reflex excitation during locomotion. This reduction may
      contribute to the tonic depression of stretch reflexes occurring in the
      decerebrate cat during locomotion.

PMID- 10922015
TI  - Circulating interleukin-6 mediates the febrile response to localised inflammation
      in rats.
AB  - Interleukin (IL)-6 is an important mediator of the host response to disease and
      has been proposed, largely based upon circumstantial evidence, as the principal
      endogenous circulating pyrogen responsible for activating CNS mechanisms in fever
      during infection and inflammation. In the present investigation, we studied the
      role of peripheral IL-6 in fever and its relationship with IL-1, itself an
      important endogenous pyrogen and a potent stimulus of IL-6 production. Injection
      of lipopolysaccharide (LPS) into a sterile, subcutaneous air pouch (i.po.) in
      rats evoked an increase in body temperature which peaked at 3 h, and which was
      abolished in animals pretreated (intraperitoneally) with IL-6 antiserum. The
      increase in body temperature was accompanied by a significant elevation in
      concentrations of (immunoreactive) IL-1 and IL-6 at the site of inflammation
      (pouch), but only IL-6 in the circulation and cerebrospinal fluids. We propose
      that much of the circulating IL-6 originates at the site of inflammation, since
      injection of human recombinant (hr)IL-6 (i.po.) was detected (10 min after the
      injection) in the plasma using an ELISA specific for human IL-6. However, despite
      the relatively high concentration of IL-6 injected (25 microg kg-1, i.po.), this
      cytokine had no effect on body temperature when injected alone, but did induce
      fever when co-injected with a non-pyrogenic dose (when given alone) of IL-1beta,
      and exacerbated the fever to a pyrogenic dose of IL-1beta. The results from the
      present study demonstrate that IL-6 is a circulating endogenous pyrogen during
      LPS-induced fever, which acts in concert with IL-1beta at the local site of
      inflammation, before entering the circulation. Circulating IL-6 can then activate
      CNS mechanisms resulting in the development of the febrile response during
      disease.

PMID- 10922016
TI  - Marathon running transiently increases c-Jun NH2-terminal kinase and p38
      activities in human skeletal muscle.
AB  - We examined the pattern of activation and deactivation of the stress-activated
      protein kinase signalling molecules c-Jun NH2-terminal kinase (JNK) and p38
      kinase in skeletal muscle in response to prolonged strenuous running exercise in
      human subjects. Male subjects (n = 14; age 32 +/- 2 years; VO2,max 60 +/- 2 ml kg
      1 min-1) completed a 42.2 km marathon (mean race time 3 h 35 min). Muscle
      biopsies were obtained 10 days prior to the marathon, immediately following the
      race, and 1, 3 and 5 days after the race. The activation of JNK and p38,
      including both p38alpha and p38gamma, was measured with immune complex assays.
      The phosphorylation state of p38 (alpha and gamma) and the upstream regulators of
      JNK and p38, mitogen-activated protein kinase kinase 4 (MKK4) and mitogen
      activated protein kinase kinase 6 (MKK6), were assessed using phosphospecific
      antibodies. JNK activity increased 7-fold over basal level immediately post
      exercise, but decreased back to basal levels 1, 3 and 5 days after the exercise.
      p38gamma phosphorylation (4-fold) and activity (1.5-fold) increased immediately
      post-exercise and returned to basal levels at 1, 3 and 5 days following exercise.
      In contrast, p38alpha phosphorylation and activity did not change over the time
      course studied. MKK4 and MKK6 phosphorylation increased and decreased in a trend
      similar to that observed with JNK activity and p38gamma phosphorylation.
      Prolonged running exercise did not affect JNK, p38alpha, or p38gamma protein
      expression in the days following the race. This study demonstrates that both JNK
      and p38 intracellular signalling cascades are robustly, yet transiently increased
      following prolonged running exercise. The differential activation of the p38
      isoforms with exercise in human skeletal muscle indicates that these proteins may
      have distinct functions in vivo.

PMID- 10922017
TI  - The force-velocity relationship of human adductor pollicis muscle during stretch
      and the effects of fatigue.
AB  - We have examined the force-velocity characteristics of tetanically activated
      human adductor pollicis working in vivo, in the fresh and fatigued states. The
      increase in force in response to stretch was divided into two major components.
      The first, steady, component persisted after the stretch and is concluded not to
      be a function of active cycling cross-bridges because it was not affected by
      either the velocity of the stretch or the level of muscle activation. The origin
      of the second, transient, component of the increased force seen during stretch is
      consistent with cross-bridge activity since it increased with increasing velocity
      of stretch and was proportional to the level of activation. It is likely that
      both components of the stretch response make a significant contribution to muscle
      performance when acting to resist a force. For the fastest stretch used, the
      contributions of cross-bridge and non-cross-bridge mechanisms were equal. For the
      slowest stretch, lasting 10 s and over the same distance, the force response was
      attributed almost entirely to non-cross-bridge mechanisms. As a result of acute
      fatigue (50 % isometric force loss) there were only small reductions in the non
      cross-bridge component of the force response to stretch, while the cross-bridge
      component decreased in absolute terms. The transient component of the stretch
      response increased as a result of fatigue, relative to the isometric force, while
      the force during shortening decreased. The results are consistent with a decrease
      in cross-bridge turnover in fatigued muscle.

PMID- 10922019
TI  - Using developmental and behavioral screening tests.

PMID- 10922018
TI  - An endogenous circadian rhythm of respiratory control in humans.
AB  - Many physiological and behavioural functions have circadian rhythms - endogenous
      oscillations with a period of approximately 24 h that can occur even in the
      absence of sleep. We determined whether there is an endogenous circadian rhythm
      in breathing, metabolism and ventilatory chemosensitivity in humans. Ten healthy,
      adult males were studied throughout 4 days in a stable laboratory environment.
      After two initial baseline days (16 h wakefulness plus 8 h sleep) that served to
      achieve a steady state, subjects were studied under constant behavioural and
      environmental conditions throughout 41 h of wakefulness. Ventilation, metabolism
      and the magnitude of the hypercapnic ventilatory response (HCVR) were measured
      every 2 h. Individuals' data were aligned according to circadian phase (core body
      temperature minimum; CBTmin) and averaged. In the group average data, there was a
      significant and large amplitude circadian variation in HCVR slope (average of +/
      0.4 l min-1 mmHg-1; corresponding to +/-12.1 % of 24 h mean), and a smaller
      amplitude rhythm in the HCVR x-axis intercept (average of +/-1.1 mmHg; +/-2.1 %
      of 24 h mean). Despite a significant circadian variation in metabolism (+/-3.2 %
      of 24 h mean), there were no detectable rhythms in tidal volume, respiratory
      frequency or ventilation. This small discrepancy between metabolism and
      ventilation led to a small but significant circadian variation in end-tidal PCO2
      (PET,CO2; +/-0.6 mmHg; +/-1.5 % of 24 h mean). The circadian minima of the group
      averaged respiratory variables occurred 6-8 h earlier than CBTmin, suggesting
      that endogenous changes in CBT across the circadian cycle have less of an effect
      on respiration than equivalent experimentally induced changes in CBT. Throughout
      these circadian changes, there were no correlations between HCVR parameters
      (slope or x-axis intercept) and either resting ventilation or resting PET,CO2.
      This suggests that ventilation and PET,CO2 are little influenced by central
      chemosensory respiratory control in awake humans even when at rest under constant
      environmental and behavioural conditions. The characteristic change in PET,CO2
      during non-rapid eye movement sleep was shown to be independent of circadian
      variations in PET,CO2, and probably reflects a change from predominantly
      behavioural to predominantly chemosensory respiratory control. This study has
      documented the existence and magnitude of circadian variations in respiration and
      respiratory control in awake humans for the first time under constant behavioural
      and environmental conditions. These results provide unique insights into
      respiratory control in awake humans, and highlight the importance of considering
      the phase of the circadian cycle in studies of respiratory control.

PMID- 10922020
TI  - Publishing proprietary screening tests

PMID- 10922021
TI  - Insect sting anaphylaxis.

PMID- 10922022
TI  - Failure to thrive: an old nemesis in the new millennium.

PMID- 10922023
TI  - The Child Behavior Checklist and related forms for assessing behavioral/emotional
      problems and competencies.

PMID- 10922024
TI  - Early detection of developmental and behavioral problems.

PMID- 10922025
TI  - Index of suspicion. Case 1. Diagnosis: infective endocarditis.

PMID- 10922027
TI  - Earning CME credit-completing the PIR quiz

PMID- 10922026
TI  - Planning the treatment of a patient who has rickets.

PMID- 10922028
TI  - Shattering the diffraction limit of light: a revolution in fluorescence
      microscopy?

PMID- 10922029
TI  - B cells in autoimmunity.

PMID- 10922030
TI  - Pathogens and hosts: the dance is the same, the couples are different.

PMID- 10922031
TI  - Striking a balance: modulation of the actin cytoskeleton by Salmonella.
AB  - Salmonella spp. have evolved the ability to enter into cells that are normally
      nonphagocytic. The internalization process is the result of a remarkable
      interaction between the bacteria and the host cells. Immediately on contact,
      Salmonella delivers a number of bacterial effector proteins into the host cell
      cytosol through the function of a specialized organelle termed the type III
      secretion system. Initially, two of the delivered proteins, SopE and SopB,
      stimulate the small GTP-binding proteins Cdc42 and Rac. SopE is an exchange
      factor for these GTPases, and SopB is an inositol polyphosphate phosphatase.
      Stimulation of Cdc42 and Rac leads to marked actin cytoskeleton rearrangements,
      which are further enhanced by SipA, a Salmonella protein also delivered into the
      host cell by the type III secretion system. SipA lowers the critical
      concentration of G-actin, stabilizes F-actin at the site of bacterial entry, and
      increases the bundling activity of the host-cell protein T-plastin (fimbrin). The
      cellular responses stimulated by Salmonella are short-lived; therefore,
      immediately after bacterial entry, the cell regains its normal architecture.
      Remarkably, this process is mediated by SptP, another target of the type III
      secretion system. SptP exert its function by serving as a GTPase-activating
      protein for Cdc42 and Rac, turning these G proteins off after their stimulation
      by the bacterial effectors SopE and SopB. The balanced interaction of Salmonella
      with host cells constitutes a remarkable example of the sophisticated nature of a
      pathogen/host relationship shaped by evolution through a longstanding
      coexistence.

PMID- 10922032
TI  - Structure and function of pectic enzymes: virulence factors of plant pathogens.
AB  - The structure and function of Erwinia chrysanthemi pectate lysase C, a plant
      virulence factor, is reviewed to illustrate one mechanism of pathogenesis at the
      molecular level. Current investigative topics are discussed in this paper.

PMID- 10922033
TI  - Pseudomonas syringae Hrp type III secretion system and effector proteins.
AB  - Pseudomonas syringae is a member of an important group of Gram-negative bacterial
      pathogens of plants and animals that depend on a type III secretion system to
      inject virulence effector proteins into host cells. In P. syringae, hrp/hrc genes
      encode the Hrp (type III secretion) system, and avirulence (avr) and Hrp
      dependent outer protein (hop) genes encode effector proteins. The hrp/hrc genes
      of P. syringae pv syringae 61, P. syringae pv syringae B728a, and P. syringae pv
      tomato DC3000 are flanked by an exchangeable effector locus and a conserved
      effector locus in a tripartite mosaic Hrp pathogenicity island (Pai) that is
      linked to a tRNA(Leu) gene found also in Pseudomonas aeruginosa but without
      linkage to Hrp system genes. Cosmid pHIR11 carries a portion of the strain 61 Hrp
      pathogenicity island that is sufficient to direct Escherichia coli and
      Pseudomonas fluorescens to inject HopPsyA into tobacco cells, thereby eliciting a
      hypersensitive response normally triggered only by plant pathogens. Large
      deletions in strain DC3000 revealed that the conserved effector locus is
      essential for pathogenicity but the exchangeable effector locus has only a minor
      role in growth in tomato. P. syringae secretes HopPsyA and AvrPto in culture in a
      Hrp-dependent manner at pH and temperature conditions associated with
      pathogenesis. AvrPto is also secreted by Yersinia enterocolitica. The secretion
      of AvrPto depends on the first 15 codons, which are also sufficient to direct the
      secretion of an Npt reporter from Y. enterocolitica, indicating that a universal
      targeting signal is recognized by the type III secretion systems of both plant
      and animal pathogens.

PMID- 10922034
TI  - Molecular and cell biology aspects of plague.
AB  - A 70-kb virulence plasmid (sometimes called pYV) enables Yersinia spp. to survive
      and multiply in the lymphoid tissues of their host. It encodes the Yop virulon, a
      system consisting of secreted proteins called Yops and their dedicated type III
      secretion apparatus called Ysc. The Ysc apparatus forms a channel composed of 29
      proteins. Of these, 10 have counterparts in almost every type III system.
      Secretion of some Yops requires the assistance, in the bacterial cytosol, of
      small individual chaperones called the Syc proteins. These chaperones act as
      bodyguards or secretion pilots for their partner Yop. Yop proteins fall into two
      categories. Some are intracellular effectors, whereas the others are
      "translocators" needed to deliver the effectors across the eukaryotic plasma
      membrane, into eukaryotic cells. The translocators (YopB, YopD, LcrV) form a pore
      of 16-23 A in the eukaryotic cell plasma membrane. The effector Yops are YopE,
      YopH, YpkA/YopO, YopP/YopJ, YopM, and YopT. YopH is a powerful phosphotyrosine
      phosphatase playing an antiphagocytic role by dephosphorylating several focal
      adhesion proteins. YopE and YopT contribute to antiphagocytic effects by
      inactivating GTPases controlling cytoskeleton dynamics. YopP/YopJ plays an anti
      inflammatory role by preventing the activation of the transcription factor NF
      kappaB. It also induces rapid apoptosis of macrophages. Less is known about the
      role of the phosphoserine kinase YopO/YpkA and YopM.

PMID- 10922036
TI  - Acyl-homoserine lactone quorum sensing in gram-negative bacteria: a signaling
      mechanism involved in associations with higher organisms.
AB  - Recent advances in studies of bacterial gene expression have brought the
      realization that cell-to-cell communication and community behavior are critical
      for successful interactions with higher organisms. Species-specific cell-to-cell
      communication is involved in successful pathogenic or symbiotic interactions of a
      variety of bacteria with plant and animal hosts. One type of cell-cell signaling
      is acyl-homoserine lactone quorum sensing in Gram-negative bacteria. This type of
      quorum sensing represents a dedicated communication system that enables a given
      species to sense when it has reached a critical population density in a host, and
      to respond by activating expression of genes necessary for continued success in
      the host. Acyl-homoserine lactone signaling in the opportunistic animal and plant
      pathogen Pseudomonas aeruginosa is a model for the relationships among quorum
      sensing, pathogenesis, and community behavior. In the P. aeruginosa model, quorum
      sensing is required for normal biofilm maturation and for virulence. There are
      multiple quorum-sensing circuits that control the expression of dozens of
      specific genes that represent potential virulence loci.

PMID- 10922037
TI  - Phenotypic variation and intracellular parasitism by histoplasma Capsulatum.
AB  - The success of Histoplasma capsulatum as an intracellular pathogen depends
      completely on successful conversion of the saprophytic mycelial (mold) form of
      this fungus to a parasitic yeast form. It is therefore not surprising that yeast
      phase-specific genes and gene products are proving to be important for survival
      and proliferation of H. capsulatum within macrophages. In this study, we have
      focused on the role and regulation of two yeast-specific characteristics: alpha
      (1,3)-glucan, a cell wall polysaccharide modulated by cell-density (quorum)
      sensing, and a secreted calcium-binding protein (CBP) that is essential for
      pathogenicity.

PMID- 10922035
TI  - A framework for interpreting the leucine-rich repeats of the Listeria
      internalins.
AB  - The surface protein InlB of the bacterial pathogen Listeria monocytogenes is
      required for inducing phagocytosis in various nonphagocytic mammalian cell types
      in vitro. InlB causes tyrosine phosphorylation of host cell adaptor proteins,
      activation of phosphoinositide 3-kinase, and rearrangements of the actin
      cytoskeleton. These events lead to phagocytic uptake of the bacterium by the host
      cell. InlB belongs to the internalin family of Listeria proteins, which also
      includes InlA, another surface protein involved in host cell invasion. The
      internalins are the largest class of bacterial proteins containing leucine-rich
      repeats (LRR), a motif associated with protein-protein interactions. The LRR
      motif is found in a functionally diverse array of proteins, including those
      involved in the plant immune system and in the mammalian innate immune response.
      Structural and functional interpretations of the sequences of internalin family
      members are presented in light of the recently determined x-ray crystal structure
      of the InlB LRR domain.

PMID- 10922038
TI  - Exploitation of host cells by enteropathogenic Escherichia coli.
AB  - Microbial pathogens have evolved many ingenious ways to infect their hosts and
      cause disease, including the subversion and exploitation of target host cells.
      One such subversive microbe is enteropathogenic Escherichia coli (EPEC). A major
      cause of infantile diarrhea in developing countries, EPEC poses a significant
      health threat to children worldwide. Central to EPEC-mediated disease is its
      colonization of the intestinal epithelium. After initial adherence, EPEC causes
      the localized effacement of microvilli and intimately attaches to the host cell
      surface, forming characteristic attaching and effacing (A/E) lesions. Considered
      the prototype for a family of A/E lesion-causing bacteria, recent in vitro
      studies of EPEC have revolutionized our understanding of how these pathogens
      infect their hosts and cause disease. Intimate attachment requires the type III
      mediated secretion of bacterial proteins, several of which are translocated
      directly into the infected cell, including the bacteria's own receptor (Tir).
      Binding to this membrane-bound, pathogen-derived protein permits EPEC to
      intimately attach to mammalian cells. The translocated EPEC proteins also
      activate signaling pathways within the underlying cell, causing the
      reorganization of the host actin cytoskeleton and the formation of pedestal-like
      structures beneath the adherent bacteria. This review explores what is known
      about EPEC's subversion of mammalian cell functions and how this knowledge has
      provided novel insights into bacterial pathogenesis and microbe-host
      interactions. Future studies of A/E pathogens in animal models should provide
      further insights into how EPEC exploits not only epithelial cells but other host
      cells, including those of the immune system, to cause diarrheal disease.

PMID- 10922039
TI  - Genetic complexity of pathogen perception by plants: the example of Rcr3, a
      tomato gene required specifically by Cf-2.
AB  - Genetic analysis of plant-pathogen interactions has demonstrated that resistance
      to infection is often determined by the interaction of dominant plant resistance
      (R) genes and dominant pathogen-encoded avirulence (Avr) genes. It was postulated
      that R genes encode receptors for Avr determinants. A large number of R genes and
      their cognate Avr genes have now been analyzed at the molecular level. R gene
      loci are extremely polymorphic, particularly in sequences encoding amino acids of
      the leucine-rich repeat motif. A major challenge is to determine how Avr
      perception by R proteins triggers the plant defense response. Mutational analysis
      has identified several genes required for the function of specific R proteins.
      Here we report the identification of Rcr3, a tomato gene required specifically
      for Cf-2-mediated resistance. We propose that Avr products interact with host
      proteins to promote disease, and that R proteins "guard" these host components
      and initiate Avr-dependent plant defense responses.

PMID- 10922040
TI  - Plants and animals share functionally common bacterial virulence factors.
AB  - By exploiting the ability of Pseudomonas aeruginosa to infect a variety of
      vertebrate and nonvertebrate hosts, we have developed model systems that use
      plants and nematodes as adjuncts to mammalian models to help elucidate the
      molecular basis of P. aeruginosa pathogenesis. Our studies reveal a remarkable
      degree of conservation in the virulence mechanisms used by P. aeruginosa to
      infect hosts of divergent evolutionary origins.

PMID- 10922041
TI  - Role of the cystic fibrosis transmembrane conductance regulator in innate
      immunity to Pseudomonas aeruginosa infections.
AB  - Chronic Pseudomonas aeruginosa infection occurs in 75-90% of patients with cystic
      fibrosis (CF). It is the foremost factor in pulmonary function decline and early
      mortality. A connection has been made between mutant or missing CF transmembrane
      conductance regulator (CFTR) in lung epithelial cell membranes and a failure in
      innate immunity leading to initiation of P. aeruginosa infection. Epithelial
      cells use CFTR as a receptor for internalization of P. aeruginosa via endocytosis
      and subsequent removal of bacteria from the airway. In the absence of functional
      CFTR, this interaction does not occur, allowing for increased bacterial loads in
      the lungs. Binding occurs between the outer core of the bacterial
      lipopolysaccharide and amino acids 108-117 in the first predicted extracellular
      domain of CFTR. In experimentally infected mice, inhibiting CFTR-mediated
      endocytosis of P. aeruginosa by inclusion in the bacterial inoculum of either
      free bacterial lipopolysaccharide or CFTR peptide 108-117 resulted in increased
      bacterial counts in the lungs. CFTR is also a receptor on gastrointestinal
      epithelial cells for Salmonella enterica serovar Typhi, the etiologic agent of
      typhoid fever. There was a significant decrease in translocation of this organism
      to the gastrointestinal submucosa in transgenic mice that are heterozygous
      carriers of a mutant DeltaF508 CFTR allele, suggesting heterozygous CFTR carriers
      may have increased resistance to typhoid fever. The identification of CFTR as a
      receptor for bacterial pathogens could underlie the biology of CF lung disease
      and be the basis for the heterozygote advantage for carriers of mutant alleles of
      CFTR.

PMID- 10922042
TI  - Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia
      coli and innate host defenses.
AB  - Strains of uropathogenic Escherichia coli (UPEC) are the causative agents in the
      vast majority of all urinary tract infections. Upon entering the urinary tract,
      UPEC strains face a formidable array of host defenses, including the flow of
      urine and a panoply of antimicrobial factors. To gain an initial foothold within
      the bladder, most UPEC strains encode filamentous surface adhesive organelles
      called type 1 pili that can mediate bacterial attachment to, and invasion of,
      bladder epithelial cells. Invasion provides UPEC with a protective environment in
      which bacteria can either replicate or persist in a quiescent state. Infection
      with type 1-piliated E. coli can trigger a number of host responses, including
      cytokine production, inflammation, and the exfoliation of infected bladder
      epithelial cells. Despite numerous host defenses and even antibiotic treatments
      that can effectively sterilize the urine, recent studies demonstrate that
      uropathogens can persist within the bladder tissue. These bacteria may serve as a
      reservoir for recurrent infections, a common problem affecting millions each
      year.

PMID- 10922043
TI  - AvrPto-dependent Pto-interacting proteins and AvrPto-interacting proteins in
      tomato.
AB  - The plant-intracellular interaction of the avirulence protein AvrPto of
      Pseudomonas syringae pathovar tomato, the agent of bacterial speck disease, and
      the corresponding tomato resistance protein Pto triggers responses leading to
      disease resistance. Pto, a serine/threonine protein kinase, also interacts with a
      putative downstream kinase, Pto-interactor 1, as well as with members of a family
      of transcription factors Pto-interactors 4, 5, and 6. These proteins are likely
      involved, respectively, in a phosphorylation cascade resulting in hypersensitive
      cell death, and in defense gene activation. The mechanism by which the
      interaction of AvrPto and Pto initiates defense response signaling is not known.
      To pursue the hypothesis that tertiary interactions are involved, we modified the
      yeast two-hybrid protein interaction trap and conducted a search for tomato
      proteins that interact with Pto only in the presence of AvrPto. Five classes of
      AvrPto-dependent Pto interactors were isolated, and their interaction specificity
      confirmed. Also, to shed light on a recently demonstrated virulence activity of
      AvrPto, we conducted a standard two-hybrid screen for tomato proteins in addition
      to Pto that interact with AvrPto: i.e., potential virulence targets or modifiers
      of AvrPto. By constructing an N-terminal rather than a C-terminal fusion of
      AvrPto to the LexA DNA binding domain, we were able to overcome autoactivation by
      AvrPto and identify four classes of specific AvrPto-interacting proteins.

PMID- 10922044
TI  - Reactive oxygen and nitrogen intermediates in the relationship between mammalian
      hosts and microbial pathogens.
AB  - This review summarizes recent evidence from knock-out mice on the role of
      reactive oxygen intermediates and reactive nitrogen intermediates (RNI) in
      mammalian immunity. Reflections on redundancy in immunity help explain an
      apparent paradox: the phagocyte oxidase and inducible nitric oxide synthase are
      each nonredundant, and yet also mutually redundant, in host defense. In
      combination, the contribution of these two enzymes appears to be greater than
      previously appreciated. The remainder of this review focuses on a relatively new
      field, the basis of microbial resistance to RNI. Experimental tuberculosis
      provides an important example of an extended, dynamic balance between host and
      pathogen in which RNI play a major role. In diseases such as tuberculosis, a
      molecular understanding of host-pathogen interactions requires characterization
      of the defenses used by microbes against RNI, analogous to our understanding of
      defenses against reactive oxygen intermediates. Genetic and biochemical
      approaches have identified candidates for RNI-resistance genes in Mycobacterium
      tuberculosis and other pathogens.

PMID- 10922046
TI  - The role of antimicrobial peptides in animal defenses.
AB  - It is becoming clear that the cationic antimicrobial peptides are an important
      component of the innate defenses of all species of life. Such peptides can be
      constitutively expressed or induced by bacteria or their products. The best
      peptides have good activities vs. a broad range of bacterial strains, including
      antibiotic-resistant isolates. They kill very rapidly, do not easily select
      resistant mutants, are synergistic with conventional antibiotics, other peptides,
      and lysozyme, and are able to kill bacteria in animal models. It is known that
      bacterial infections, especially when treated with antibiotics, can lead to the
      release of bacterial products such as lipopolysaccharide (LPS) and lipoteichoic
      acid, resulting in potentially lethal sepsis. In contrast to antibiotics, the
      peptides actually prevent cytokine induction by bacterial products in tissue
      culture and human blood, and they block the onset of sepsis in mouse models of
      endotoxemia. Consistent with this, transcriptional gene array experiments using a
      macrophage cell line demonstrated that a model peptide, CEMA, blocks the
      expression of many genes whose transcription was induced by LPS. The peptides do
      this in part by blocking LPS interaction with the serum protein LBP. In addition,
      CEMA itself has a direct effect on macrophage gene expression. Because cationic
      antimicrobial peptides are induced by LPS and are able to dampen the septic
      response of animal cells to LPS, we propose that, in addition to their role in
      direct and lysozyme-assisted killing of microbes, they have a role in feedback
      regulation of cytokine responses. We are currently developing variant peptides as
      therapeutics against antibiotic-resistant infections.

PMID- 10922048
TI  - Toward elimination of discrepancies between theory and experiment: the rate
      constant of the atmospheric conversion of SO3 to H2SO4.
AB  - The hydration rate constant of sulfur trioxide to sulfuric acid is shown to
      depend sensitively on water vapor pressure. In the 1:1 SO3-H2O complex, the rate
      is predicted to be slower by about 25 orders of magnitude compared with
      laboratory results [Lovejoy, E. R., Hanson, D. R. & Huey, L. G. (1996) J. Phys.
      Chem. 100, 19911-19916; Jayne, J. T., Poschl, U., Chen, Y.-m., Dai, D., Molina,
      L. T., Worsnop, D. R., Kolb, C. E. & Molina, M. J. (1997) J. Phys. Chem. A 101,
      10000-10011]. This discrepancy is removed mostly by allowing a second and third
      water molecule to participate. An asynchronous water-mediated double proton
      transfer concerted with the nucleophilic attack and a double proton transfer
      accompanied by a transient H3O+ rotation are predicted to be the fastest reaction
      mechanisms. Comparison of the predicted negative apparent "activation" energies
      with the experimental finding indicates that in our atmosphere, different
      reaction paths involving two and three water molecules are taken in the process
      of forming sulfate aerosols and consequently acid rain.

PMID- 10922045
TI  - Nitric oxide and salicylic acid signaling in plant defense.
AB  - Salicylic acid (SA) plays a critical signaling role in the activation of plant
      defense responses after pathogen attack. We have identified several potential
      components of the SA signaling pathway, including (i) the H(2)O(2)-scavenging
      enzymes catalase and ascorbate peroxidase, (ii) a high affinity SA-binding
      protein (SABP2), (iii) a SA-inducible protein kinase (SIPK), (iv) NPR1, an
      ankyrin repeat-containing protein that exhibits limited homology to IkappaBalpha
      and is required for SA signaling, and (v) members of the TGA/OBF family of bZIP
      transcription factors. These bZIP factors physically interact with NPR1 and bind
      the SA-responsive element in promoters of several defense genes, such as the
      pathogenesis-related 1 gene (PR-1). Recent studies have demonstrated that nitric
      oxide (NO) is another signal that activates defense responses after pathogen
      attack. NO has been shown to play a critical role in the activation of innate
      immune and inflammatory responses in animals. Increases in NO synthase (NOS)-like
      activity occurred in resistant but not susceptible tobacco after infection with
      tobacco mosaic virus. Here we demonstrate that this increase in activity
      participates in PR-1 gene induction. Two signaling molecules, cGMP and cyclic ADP
      ribose (cADPR), which function downstream of NO in animals, also appear to
      mediate plant defense gene activation (e.g., PR-1). Additionally, NO may activate
      PR-1 expression via an NO-dependent, cADPR-independent pathway. Several targets
      of NO in animals, including guanylate cyclase, aconitase, and mitogen-activated
      protein kinases (e.g., SIPK), are also modulated by NO in plants. Thus, at least
      portions of NO signaling pathways appear to be shared between plants and animals.

PMID- 10922049
TI  - Information theory, atoms in molecules, and molecular similarity.
AB  - Using information theory, it is argued that from among possible definitions of
      what an atom is when it is in a molecule, a particular one merits special
      attention. Namely, it is the atom defined by the "stockholders partitioning" of a
      molecule invented by Hirshfeld [(1977) Theor. Chim. Acta 44, 129]. The
      theoretical tool used is the minimum entropy deficiency principle (minimum
      missing information principle) of Kullback and Liebler [(1951) Ann. Math. Stat.
      22, 79]. A corresponding analysis is given of the problem of assessing similarity
      between molecules or pieces of molecules.

PMID- 10922047
TI  - Suramin inhibits initiation of defense signaling by systemin, chitosan, and a
      beta-glucan elicitor in suspension-cultured Lycopersicon peruvianum cells.
AB  - Systemin-mediated defense signaling in tomato (Lycopersicon esculentum) plants is
      analogous to the cytokine-mediated inflammatory response in animals. Herein, we
      report that the initiation of defense signaling in suspension-cultured cells of
      Lycopersicon peruvianum by the peptide systemin, as well as by chitosan and beta
      glucan elicitor from Phytophtora megasperma, is inhibited by the polysulfonated
      naphtylurea compound suramin, a known inhibitor of cytokine and growth factor
      receptor interactions in animal cells. Using a radioreceptor assay, we show that
      suramin interfered with the binding of the systemin analog (125)I-Tyr-2, Ala-15
      systemin to the systemin receptor with an IC(50) of 160 microM. Additionally,
      labeling of the systemin receptor with a photoaffinity analog of systemin was
      inhibited in the presence of suramin. Receptor-mediated tyrosine phosphorylation
      of a 48-kDa mitogen-activated protein kinase and alkalinization of the medium of
      suspension-cultured cells in response to systemin and carbohydrate elicitors were
      also inhibited by suramin. The inhibition of medium alkalinization by suramin was
      reversible in the presence of high concentrations of systemin and carbohydrate
      elicitors. Calyculin A and erythrosin B, intracellular inhibitors of phosphatases
      and plasma membrane proton ATPases, respectively, both induce medium
      alkalinization, but neither response was inhibited by suramin. The polysulfonated
      compound heparin did not inhibit systemin-induced medium alkalinization. NF 007,
      a suramin derivative, induced medium alkalinization, indicating that neither NF
      007 nor heparin interact with elicitor receptors like suramin. The data indicate
      that cell-surface receptors in plants show some common structural features with
      animal cytokine and growth factor receptors that can interact with suramin to
      interfere with ligand binding.

PMID- 10922050
TI  - The N terminus of microsomal delta 9 stearoyl-CoA desaturase contains the
      sequence determinant for its rapid degradation.
AB  - Stearoyl-CoA desaturase (SCD) is a key regulator of membrane fluidity, turns over
      rapidly, and represents a model for selective degradation of short-lived proteins
      of the endoplasmic reticulum (ER). The mechanism whereby specific ER proteins are
      targeted for degradation in the midst of stable proteins coexisting in the same
      membrane is unknown. To investigate the intracellular fate of SCD and to identify
      the determinants involved in the rapid turnover of SCD, we created chimeras of
      SCD tagged at the C terminus with the green fluorescent protein (GFP). The fusion
      proteins were expressed in Chinese hamster ovary cells and exhibited an ER
      localization. Unlike native GFP, the SCD-GFP construct was unstable and had a
      half life of a few hours. Truncated fusion proteins consisting of residues 27-358
      and 45-358 of SCD linked to the N terminus of GFP were stable. To investigate the
      general applicability of the N terminus of SCD in the destabilization of
      proteins, we fused residues 1-33 of SCD to the N terminus of GFP. The resulting
      chimera was extremely short lived. To investigate the effect of membrane
      sidedness on the fusion protein degradation, we attached a lumenal targeting
      signal to the N terminus of SCD 1-33-GFP. The construct was localized to the
      lumen of ER and was metabolically stable, indicating that SCD degradation signal
      functions on the cytosolic rather than the lumenal side of the ER. These results
      demonstrate that the N-terminal segment of some 30 residues of SCD constitutes a
      motif responsible for the rapid degradation of SCD.

PMID- 10922051
TI  - Protein binding and unfolding by the chaperone ClpA and degradation by the
      protease ClpAP.
AB  - ClpA, a bacterial member of the Clp/Hsp100 chaperone family, is an ATP-dependent
      molecular chaperone and the regulatory component of the ATP-dependent ClpAP
      protease. To study the mechanism of binding and unfolding of proteins by ClpA and
      translocation to ClpP, we used as a model substrate a fusion protein that joined
      the ClpA recognition signal from RepA to green fluorescent protein (GFP). ClpAP
      degrades the fusion protein in vivo and in vitro. The substrate binds
      specifically to ClpA in a reaction requiring ATP binding but not hydrolysis.
      Binding alone is not sufficient to destabilize the native structure of the GFP
      portion of the fusion protein. Upon ATP hydrolysis the GFP fusion protein is
      unfolded, and the unfolded intermediate can be sequestered by ClpA if a
      nonhydrolyzable analog is added to displace ATP. ATP is required for release. We
      found that although ClpA is unable to recognize native proteins lacking
      recognition signals, including GFP and rhodanese, it interacts with those same
      proteins when they are unfolded. Unfolded GFP is held in a nonnative conformation
      while associated with ClpA and its release requires ATP hydrolysis. Degradation
      of unfolded untagged proteins by ClpAP requires ATP even though the initial ATP
      dependent unfolding reaction is bypassed. These results suggest that there are
      two ATP-requiring steps: an initial protein unfolding step followed by
      translocation of the unfolded protein to ClpP or in some cases release from the
      complex.

PMID- 10922052
TI  - Unfolding and internalization of proteins by the ATP-dependent proteases ClpXP
      and ClpAP.
AB  - ClpX and ClpA are molecular chaperones that interact with specific proteins and,
      together with ClpP, activate their ATP-dependent degradation. The chaperone
      activity is thought to convert proteins into an extended conformation that can
      access the sequestered active sites of ClpP. We now show that ClpX can catalyze
      unfolding of a green fluorescent protein fused to a ClpX recognition motif (GFP
      SsrA). Unfolding of GFP-SsrA depends on ATP hydrolysis. GFP-SsrA unfolded either
      by ClpX or by treatment with denaturants binds to ClpX in the presence of
      adenosine 5'-O-(3-thiotriphosphate) and is released slowly (t(1/2) approximately
      15 min). Unlike ClpA, ClpX cannot trap unfolded proteins in stable complexes
      unless they also have a high-affinity binding motif. Addition of ATP or ADP
      accelerates release (t(1/2) approximately 1 min), consistent with a model in
      which ATP hydrolysis induces a conformation of ClpX with low affinity for
      unfolded substrates. Proteolytically inactive complexes of ClpXP and ClpAP unfold
      GFP-SsrA and translocate the protein to ClpP, where it remains unfolded.
      Complexes of ClpXP with translocated substrate within the ClpP chamber retain the
      ability to unfold GFP-SsrA. Our results suggest a bipartite mode of interaction
      between ClpX and substrates. ClpX preferentially targets motifs exposed in
      specific proteins. As the protein is unfolded by ClpX, additional motifs are
      exposed that facilitate its retention and favor its translocation to ClpP for
      degradation.

PMID- 10922053
TI  - Mouse Sebox homeobox gene expression in skin, brain, oocytes, and two-cell
      embryos.
AB  - Sebox is a mouse paired-like homeobox gene, previously named OG-9. Sebox genomic
      DNA and cDNA were cloned and sequenced. In addition, rat and human Sebox genomic
      DNAs were cloned and sequenced, and the predicted amino acid sequences were
      compared. The mouse Sebox gene was mapped to chromosome 11 near the Evi 2 locus.
      The mouse Sebox gene is expressed in brain, skin, ovary, and liver of mice. In
      the brain, the Sebox gene is expressed in the cerebral cortex and CA areas of the
      hippocampus, pontine nuclei, choroid plexus, and the cerebellum. Northern
      analysis and RNase protection assays revealed low levels of Sebox RNA in 12-day
      mouse embryos and higher levels in 18- and 19-day embryos. In late embryos and
      newborn mice, Sebox expression is localized in the epidermis. In adult mice,
      Sebox RNA was found in maturing oocytes and in fertilized eggs; however, the
      abundance of Sebox RNA is decreased in the two-cell embryo, and little or none
      was detected in the four-cell embryo. Hence, Sebox is a maternally expressed
      homeobox gene.

PMID- 10922054
TI  - Hydrolytic editing by a class II aminoacyl-tRNA synthetase.
AB  - Editing reactions catalyzed by aminoacyl-tRNA synthetases are critical for
      accurate translation of the genetic code. To date, this activity, whereby
      misactivated amino acids are hydrolyzed either before or after transfer to
      noncognate tRNAs, has been characterized extensively only in the case of class I
      synthetases. Class II synthetases have an active-site architecture that is
      completely distinct from that of class I. Thus, findings on editing by class I
      synthetases may not be applicable generally to class II enzymes. Class II
      Escherichia coli proline-tRNA synthetase is shown here to misactivate alanine and
      to hydrolyze the noncognate amino acid before transfer to tRNA(Pro). This enzyme
      also is capable of rapidly deacylating a mischarged Ala-tRNA(Pro) variant. A
      single cysteine residue (C443) that is located within the class II-specific motif
      3 consensus sequence was shown previously to be dispensable for proline-tRNA
      synthetase aminoacylation activity. We show here that C443 is critical for the
      hydrolytic editing of Ala-tRNA(Pro) by this class II synthetase.

PMID- 10922055
TI  - Ribozyme-mediated inhibition of HIV 1 suggests nucleolar trafficking of HIV-1
      RNA.
AB  - The HIV regulatory proteins Tat and Rev have a nucleolar localization property in
      human cells. However, no functional role has been attributed to this
      localization. Recently it has been demonstrated that expression of Rev induces
      nucleolar relocalization of some protein factors involved in Rev export. Because
      the function of Rev is to bind HIV RNA and facilitate transport of singly spliced
      and unspliced RNA to the cytoplasm, it is likely that the nucleolus plays a
      critical role in HIV-1 RNA export. As a test for trafficking of HIV-1 RNAs into
      the nucleolus, a hammerhead ribozyme that specifically cleaves HIV-1 RNA was
      inserted into the body of the U16 small nucleolar RNA, resulting in accumulation
      of the ribozyme within the nucleoli of human cells. HeLa CD4(+) and T cells
      expressing this nucleolar localized ribozyme exhibit dramatically suppressed HIV
      1 replication. The results presented here suggest a trafficking of HIV-1 RNA
      through the nucleoli of human cells, thus posing a different paradigm for
      lentiviral RNA processing.

PMID- 10922056
TI  - The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to
      ubiquitinate substrates of the anaphase-promoting complex.
AB  - The anaphase-promoting complex (APC) is a cell cycle-regulated ubiquitin-protein
      ligase that targets cyclin B, securin and other destruction box containing
      proteins for proteolysis. Nine APC subunits have been identified in vertebrates
      and eleven in yeast, but for none of them it is known how they contribute to the
      catalysis of ubiquitination reactions. Here we report the mass spectrometric
      identification of CDC26 and of the RING-H2 finger protein APC11 in the human APC.
      We have expressed these proteins and several other APC subunits in Escherichia
      coli and have tested their activities in vitro. We find that APC11 alone is
      sufficient to allow the synthesis of multiubiquitin chains in the presence of E1
      and UBC4. These multiubiquitin chains are partly unanchored and partly bound to
      APC11 itself. APC11 and UBC4 are also able to ubiquitinate securin and cyclin B,
      but these reactions show a decreased dependency on the destruction box. The
      integrity of the putative zinc binding RING-H2 finger is required for the ability
      of APC11 to support ubiquitination reactions. These results suggest that APC11
      and UBC4 catalyze the formation of isopeptide bonds in APC-mediated
      ubiquitination reactions.

PMID- 10922057
TI  - Accurate and rapid docking of protein-protein complexes on the basis of
      intermolecular nuclear overhauser enhancement data and dipolar couplings by rigid
      body minimization.
AB  - A simple and rapid method is presented for solving the three-dimensional
      structures of protein-protein complexes in solution on the basis of experimental
      NMR restraints that provide the requisite translational (i.e., intermolecular
      nuclear Overhauser enhancement, NOE, data) and orientational (i.e., backbone (1)H
      (15)N dipolar couplings and intermolecular NOEs) information. Providing high
      resolution structures of the proteins in the unbound state are available and no
      significant backbone conformational changes occur upon complexation (which can
      readily be assessed by analysis of dipolar couplings measured on the complex),
      accurate and rapid docking of the two proteins can be achieved. The method, which
      is demonstrated for the 40-kDa complex of enzyme I and the histidine
      phosphocarrier protein, involves the application of rigid body minimization using
      a target function comprising only three terms, namely experimental NOE-derived
      intermolecular interproton distance and dipolar coupling restraints, and a simple
      intermolecular van der Waals repulsion potential. This approach promises to
      dramatically reduce the amount of time and effort required to solve the
      structures of protein-protein complexes by NMR, and to extend the capabilities of
      NMR to larger protein-protein complexes, possibly up to molecular masses of 100
      kDa or more.

PMID- 10922058
TI  - Energetics of the HIV gp120-CD4 binding reaction.
AB  - HIV infection is initiated by the selective interaction between the cellular
      receptor CD4 and gp120, the external envelope glycoprotein of the virus. We used
      analytical ultracentrifugation, titration calorimetry, and surface plasmon
      resonance biosensor analysis to characterize the assembly state, thermodynamics,
      and kinetics of the CD4-gp120 interaction. The binding thermodynamics were of
      unexpected magnitude; changes in enthalpy, entropy, and heat capacity greatly
      exceeded those described for typical protein-protein interactions. These unusual
      thermodynamic properties were observed with both intact gp120 and a
      deglycosylated and truncated form of gp120 protein that lacked hypervariable
      loops V1, V2, and V3 and segments of its N and C termini. Together with previous
      crystallographic studies, the large changes in heat capacity and entropy reveal
      that extensive structural rearrangements occur within the core of gp120 upon CD4
      binding. CD spectral studies and slow kinetics of binding support this
      conclusion. These results indicate considerable conformational flexibility within
      gp120, which may relate to viral mechanisms for triggering infection and
      disguising conserved receptor-binding sites from the immune system.

PMID- 10922059
TI  - The NF-kappa B signal transduction pathway in aortic endothelial cells is primed
      for activation in regions predisposed to atherosclerotic lesion formation.
AB  - Atherosclerotic lesions form at distinct sites in the arterial tree, suggesting
      that hemodynamic forces influence the initiation of atherogenesis. If NF-kappaB
      plays a role in atherogenesis, then the activation of this signal transduction
      pathway in arterial endothelium should show topographic variation. The expression
      of NF-kappaB/IkappaB components and NF-kappaB activation was evaluated by
      specific antibody staining, en face confocal microscopy, and image analysis of
      endothelium in regions of mouse proximal aorta with high and low probability (HP
      and LP) for atherosclerotic lesion development. In control C57BL/6 mice,
      expression levels of p65, IkappaBalpha, and IkappaBbeta were 5- to 18-fold higher
      in the HP region, yet NF-kappaB was activated in a minority of endothelial cells.
      This suggested that NF-kappaB signal transduction was primed for activation in HP
      regions on encountering an activation stimulus. Lipopolysaccharide treatment or
      feeding low-density lipoprotein receptor knockout mice an atherogenic diet
      resulted in NF-kappaB activation and up-regulated expression of NF-kappaB
      inducible genes predominantly in HP region endothelium. Preferential regional
      activation of endothelial NF-kappaB by systemic stimuli, including
      hypercholesterolemia, may contribute to the localization of atherosclerotic
      lesions at sites with high steady-state expression levels of NF-kappaB/IkappaB
      components.

PMID- 10922060
TI  - The junctional multidomain protein AF-6 is a binding partner of the Rap1A GTPase
      and associates with the actin cytoskeletal regulator profilin.
AB  - The AF-6 protein is a multidomain protein that contains two potential Ras-binding
      domains within its N terminus. Because of this feature, AF-6 has been isolated in
      both two-hybrid and biochemical approaches and is postulated to be a potential
      Ras-effector protein. Herein, we show that it is specifically the first Ras
      binding domain of AF-6 that mediates this interaction and that the Ras-related
      Rap1A protein can associate with this motif even more efficiently than the
      oncogenic Ha-, K-, and N-Ras GTPases. We further demonstrate that both Ras and
      Rap1 interact with full-length AF-6 in vivo in mammalian cells and that a
      fraction of Rap1 colocalizes with AF-6 at the membrane. Dominant active Rap1A, in
      contrast to Ras, when introduced into epithelial MDCK and MCF-7 cells, does not
      perturb AF-6-specific residency in cell-cell adhesion complexes. In a pursuit to
      gain further understanding of the role of AF-6 in junctions, we identified
      profilin as an AF-6-binding protein. Profilin activates monomeric actin units for
      subsequent polymerization steps at barbed ends of actin filaments and has been
      shown to participate in cortical actin assembly. To our knowledge, AF-6 is the
      only integral component in cell-cell junctions discovered thus far that interacts
      with profilin and thus could modulate actin modeling proximal to adhesion
      complexes.

PMID- 10922061
TI  - Neisseria meningitidis porin PorB interacts with mitochondria and protects cells
      from apoptosis.
AB  - Neisserial porins are strong immune adjuvants and B cell activators. The effect
      of neisserial porin PorB on activation-induced cell death was investigated, as a
      potential additional mechanism of the porin's immunopotentiating ability.
      Neisserial porins interact with target cells to localize intracellularly in the
      mitochondrial compartment without negatively affecting cellular survival.
      Pretreatment with Neisseria meningitidis PorB porin decreased or abrogated the
      mitochondrial damage induced by apoptotic stimuli. In addition, end stage
      determinants of apoptosis, including DNA breakdown, were diminished by PorB.
      Immunoprecipitation experiments revealed that PorB interacts with the
      mitochondrial porin VDAC (voltage-dependent anion channel). The mechanism of the
      antiapoptotic effect of neisserial porins could be explained by the protein
      protein interaction of PorB with VDAC, similar to the interaction of VDAC with
      antiapoptotic Bcl-2 proteins, resulting in an enhancement of cell survival and
      continued activation of B cells.

PMID- 10922063
TI  - Expression of the gene encoding the proapoptotic Nip3 protein is induced by
      hypoxia.
AB  - The ability to sense and respond to changes in oxygen availability is critical
      for many developmental, physiological, and pathological processes, including
      angiogenesis, control of blood pressure, and cerebral and myocardial ischemia.
      Hypoxia-inducible factor-1alpha (HIF-1alpha) is a basic-helix-loop-helix
      (bHLH)containing member of the PER-ARNT-SIM (PAS) family of transcription factors
      that plays a central role in the response to hypoxia. HIF-1alpha, and its
      relatives HIF-2alpha/endothelial PAS domain protein (EPAS) and HIF-3alpha, are
      induced in response to hypoxia and serve to coordinately activate the expression
      of target genes whose products facilitate cell survival under conditions of
      oxygen deprivation. When cells are exposed to chronic hypoxia, the protective
      response can fail, resulting in apoptosis. This study shows that transcription of
      the gene encoding Nip3, a proapoptotic member of the Bcl-2 family of cell death
      factors, is strongly induced in response to hypoxia. The Nip3 promoter contains a
      functional HIF-1-responsive element (HRE) and is potently activated by both
      hypoxia and forced expression of HIF-1alpha. Exposure of cultured cells to
      chronic hypoxia results in the accumulation of a protein recognized by antibodies
      raised against Nip3. This study demonstrates a direct link between HIF-1alpha and
      a proapoptotic member of the Bcl-2 family and offers a reasonable physiological
      function for members of the Bcl-2 subfamily, including Nip3 and its close
      relative Nix. These observations indicate that Nip3 may play a dedicated role in
      the pathological progression of hypoxia-mediated apoptosis, as observed after
      ischemic injury.

PMID- 10922062
TI  - Paxillin alpha and Crk-associated substrate exert opposing effects on cell
      migration and contact inhibition of growth through tyrosine phosphorylation.
AB  - Protein tyrosine phosphorylation accompanies and is essential for integrin
      signaling. We have shown that tyrosine phosphorylation of paxillin alpha and Crk
      associated substrate (p130(Cas)) is a prominent event on integrin activation in
      normal murine mammary gland epithelial cells. Tyrosine phosphorylation of
      p130(Cas) has been demonstrated to facilitate cell migration. We show here that
      tyrosine phosphorylation of paxillin alpha acts to reduce haptotactic cell
      migrations as well as transcellular invasive activities in several different
      experimental cell systems, whereas tyrosine phosphorylation of p130(Cas) exerts
      opposing effects to those of paxillin alpha. Each of the phosphorylation-null
      mutants acts as a dominant negative for each phenotype. Moreover, we found that
      overexpression of paxillin alpha reduced the cell saturation density of normal
      murine mammary gland cells, whereas overexpression of p130(Cas) increased it.
      These effects also seemed to depend on tyrosine phosphorylation events. Cell
      growth rates and morphologies at growing phases were not significantly altered,
      nor were cells transformed. Addition of epidermal growth factor increased
      saturation density of the paxillin alpha-overexpressing cells, whereas no further
      increment was observed in p130(Cas)-overexpressing cells. We propose that
      tyrosine phosphorylation of paxillin alpha and p130(Cas) exerts opposing effects
      on several integrin-mediated cellular events, possibly through different
      signaling pathways.

PMID- 10922064
TI  - Gastrulation defective is a serine protease involved in activating the receptor
      toll to polarize the Drosophila embryo.
AB  - The dorsoventral axis of the Drosophila embryo is induced by a ventrally
      restricted ligand for the receptor Toll. The Toll ligand is generated by a
      proteolytic processing reaction, which occurs at the end of a proteolytic cascade
      and requires the gastrulation defective (gd), nudel, pipe, and windbeutel genes.
      Here we demonstrate that the GD protein is a serine protease and that the three
      other genes act to restrict GD activity to the ventral side of the embryo. Our
      data support a model in which the GD protease catalyzes the ventral activation of
      the proteolytic cascade that produces the Toll ligand.

PMID- 10922066
TI  - Placental expression of the nonclassical MHC class I molecule Mamu-AG at
      implantation in the rhesus monkey.
AB  - During human implantation trophoblasts mediate attachment of the embryo to the
      uterine epithelium and invade and reorganize vessels of the maternal endometrium
      to initiate blood flow to the intervillous space. Expression of the nonclassical
      MHC class I molecule HLA-G by invading trophoblasts may play a central role in
      their protection from recognition by the maternal immune system; however, the
      ontogeny of trophoblast HLA-G expression during the earliest stages of
      implantation is difficult to evaluate in human pregnancy. We previously
      identified a novel nonclassical MHC class I molecule, Mamu-AG, which is expressed
      in the rhesus monkey placenta and shares many unique characteristics of HLA-G.
      Immunocytochemical analysis with a Mamu-AG-specific mAb and locus-specific in
      situ hybridization of rhesus implantation sites 7-12 days after embryo attachment
      (days 14-19 of pregnancy) demonstrated that Mamu-AG molecules are expressed
      predominantly in cytotrophoblasts invading the maternal vessels and endometrium,
      whereas syncytiotrophoblasts covering trophoblastic lacunae or newly formed
      chorionic villi remained largely Mamu-AG-negative. By day 36 of pregnancy, Mamu
      AG glycoprotein also was expressed in villous syncytiotrophoblasts, and
      accumulation of Mamu-AG glycoprotein was noted at the border between maternal
      decidua and fetal trophoblasts. The ontogeny of a nonclassical MHC class I
      molecule at the implantation site supports the hypothesis that its expression is
      important for the establishment of maternal-fetal immune tolerance.

PMID- 10922067
TI  - Evolutionary consequences of changes in species' geographical distributions
      driven by Milankovitch climate oscillations.
AB  - We suggest Milankovitch climate oscillations as a common cause for geographical
      patterns in species diversity, species' range sizes, polyploidy, and the degree
      of specialization and dispersability of organisms. Periodical changes in the
      orbit of the Earth cause climatic changes termed Milankovitch oscillations,
      leading to large changes in the size and location of species' geographical
      distributions. We name these recurrent changes "orbitally forced species' range
      dynamics" (ORD). The magnitude of ORD varies in space and time. ORD decreases
      gradual speciation (attained by gradual changes over many generations), increases
      range sizes and the proportions of species formed by polyploidy and other
      "abrupt" mechanisms, selects against specialization, and favor dispersability.
      Large ORD produces species prone neither to extinction nor gradual speciation.
      ORD increases with latitude. This produces latitudinal patterns, among them the
      gradient in species diversity and species' range sizes (Rapoport's rule).
      Differential ORD and its evolutionary consequences call for new conservation
      strategies on the regional to global scale.

PMID- 10922065
TI  - Spatial control of cell differentiation in Myxococcus xanthus.
AB  - Myxococcus xanthus develops species-specific multicellular fruiting bodies.
      Starting from a uniform mat of cells, some cells enter into nascent fruiting body
      aggregates, whereas other cells remain outside. The cells within the fruiting
      body differentiate from rods into spherical, heat-resistant spores, whereas the
      cells outside the aggregates, called peripheral cells, remain rod-shaped. Early
      developmentally regulated genes are expressed in peripheral cells as well as by
      cells in the fruiting bodies. By contrast, late developmental genes are only
      expressed by cells within the nascent fruiting bodies. The data show that
      peripheral cells begin to develop, but are unable to express genes that are
      switched on later than about 6 h after the start of development. All of the genes
      whose expression is limited to the fruiting body are dependent on C-signaling
      either directly or indirectly, whereas the genes that are equally expressed in
      peripheral rods and in fruiting body cells are not. One of the C-signal-dependent
      and spatially patterned operons is called dev, and the dev operon has been
      implicated in the process of sporulation. It is proposed that expression of
      certain genes, including those of the dev operon, is limited to the nascent
      fruiting body because fruiting body cells engage in a high level of C-signaling.
      Peripheral cells do less C-signaling than fruiting body cells, because they have
      a different spatial arrangement and are at lower density. As a consequence,
      peripheral cells fail to express the late genes necessary for spore
      differentiation.

PMID- 10922068
TI  - Genome-wide expression profiling of mid-gestation placenta and embryo using a
      15,000 mouse developmental cDNA microarray.
AB  - cDNA microarray technology has been increasingly used to monitor global gene
      expression patterns in various tissues and cell types. However, applications to
      mammalian development have been hampered by the lack of appropriate cDNA
      collections, particularly for early developmental stages. To overcome this
      problem, a PCR-based cDNA library construction method was used to derive 52,374
      expressed sequence tags from pre- and peri-implantation embryos, embryonic day
      (E) 12.5 female gonad/mesonephros, and newborn ovary. From these cDNA
      collections, a microarray representing 15,264 unique genes (78% novel and 22%
      known) was assembled. In initial applications, the divergence of placental and
      embryonic gene expression profiles was assessed. At stage E12.5 of development,
      based on triplicate experiments, 720 genes (6.5%) displayed statistically
      significant differences in expression between placenta and embryo. Among 289 more
      highly expressed in placenta, 61 placenta-specific genes encoded, for example, a
      novel prolactin-like protein. The number of genes highly expressed (and
      frequently specific) for placenta has thereby been increased 5-fold over the
      total previously reported, illustrating the potential of the microarrays for
      tissue-specific gene discovery and analysis of mammalian developmental programs.

PMID- 10922069
TI  - 3' poly(A) is dispensable for translation.
AB  - In wild-type cells, the 3' poly(A) structure is necessary for translation of mRNA
      and for mRNA stability. The superkiller 2 (ski2), ski3, ski6, ski7, and ski8
      mutations enhance the expression of the poly(A)(-) mRNAs of yeast RNA viruses.
      Ski2p is a DEVH-box RNA helicase and Slh1p resembles Ski2p. Both repress L-A
      double-stranded RNA (dsRNA) virus copy number, further suggesting that their
      functions may overlap. We find that slh1Delta ski2Delta double mutants are
      healthy (in the absence of viruses) and show normal rates of turnover of several
      cellular mRNAs. The slh1Delta ski2Delta strains translate electroporated
      nonpoly(A) mRNA with the same kinetics as polyA(+) mRNA. Thus, the translation
      apparatus is inherently capable of efficiently using nonpoly(A) mRNA even in the
      presence of normal amounts of competing poly(A)(+) mRNA, but is normally
      prevented from doing so by the combined action of the nonessential proteins Ski2p
      and Slh1p.

PMID- 10922070
TI  - Prediction, identification, and artificial selection of DNA rearrangements in
      Rhizobium: toward a natural genomic design.
AB  - Based on the DNA sequence of the symbiotic plasmid of Rhizobium strain NGR234, we
      predicted potential rearrangements generated by homologous recombination. All
      predicted rearrangements were identified experimentally by using a PCR-based
      methodology. Thus, the predicted and the actual dynamic maps of the replicon
      coincide. By using an approach that does not involve the introduction of
      exogenous genetic elements, derivative populations that are pure for specific
      rearrangements were obtained. We propose that knowledge of the DNA sequence of a
      genome offers the possibility of designing pathways of sequential rearrangements
      leading to alternative genomic structures. An experimental strategy to isolate
      bacterial populations containing the desired structures is discussed.

PMID- 10922071
TI  - T cell homeostasis in patients with rheumatoid arthritis.
AB  - The immune system is equipped with an extremely large spectrum of structurally
      diverse receptors to recognize all potential antigens. This fundamental principle
      of receptor diversity is no longer upheld in patients with rheumatoid arthritis
      (RA), who have a marked contraction of the T cell receptor repertoire. In this
      study, the ability of RA patients to produce T cells and to maintain T cell
      homeostasis was examined. CD4 T cells containing T cell receptor rearrangement
      excision circles (TREC) were substantially reduced in RA patients; TREC levels in
      young adult patients matched those of controls 20 years older. Increased self
      replication of T cells in RA was indicated by age-inappropriate erosion of
      telomeres in circulating T cells with almost complete attrition of telomeric
      reserves in patients 20-30 yr of age. The degree of telomere loss was not related
      to disease duration or the use of disease-modifying medication and was most
      pronounced in CD4(+)CD45RO(null) (naive) T cells. The loss of TREC-positive T
      cells could be a consequence of a primary defect in peripheral T cell
      homeostasis. Alternatively, RA patients may have impaired thymic function with
      the increased turnover of peripheral T cells being a secondary compensatory
      event.

PMID- 10922073
TI  - Intratumoral injection of adenoviral vectors encoding tumor-targeted
      immunoconjugates for cancer immunotherapy.
AB  - The efficacy and safety of a new immunotherapy protocol for cancer were tested in
      a severe combined immunodeficient mouse model of human skin and metastatic lung
      melanoma. The protocol involves intratumoral injections of replication
      incompetent adenoviral vectors encoding immunoconjugates composed of the Fc
      region of an IgG1 immunoglobulin conjugated to a tumor-targeting domain. One
      targeting domain is factor VII that binds to tissue factor expressed on
      endothelial cells lining the tumor neovasculature and on tumor cells; the active
      site of factor VII was mutated to inhibit the initiation of blood coagulation.
      Another targeting domain is a single-chain Fv antibody that binds to a cognate
      antigen expressed on human melanoma cells. The adenoviral vectors infect mainly
      the cells of the injected tumor, which synthesize and secrete the
      immunoconjugates. The bloodborne immunoconjugates induce a cytolytic immune
      response against the targeted neovasculature endothelial cells and tumor cells.
      The mouse model experiments showed that intratumoral delivery of the factor VII
      immunoconjugate, either alone or together with the single-chain Fv
      immunoconjugate, resulted in growth inhibition and regression of the injected
      tumor, and also of distant metastatic tumors, without evidence of damage to
      normal organs. There was extensive destruction of the tumor neovasculature,
      presumably mediated by the factor VII immunoconjugate bound to tissue factor on
      neovasculature endothelial cells. Because tissue factor is generally expressed on
      neovascular endothelial cells and tumor cells, a factor VII immunoconjugate could
      be used for immunotherapy against a broad range of human solid tumors.

PMID- 10922072
TI  - Conditional up-regulation of MHC class I in skeletal muscle leads to self
      sustaining autoimmune myositis and myositis-specific autoantibodies.
AB  - In the human inflammatory myopathies (polymyositis and dermatomyositis), the
      early, widespread appearance of MHC class I on the surface of muscle cells and
      the occurrence of certain myositis-specific autoantibodies are striking features.
      We have used a controllable muscle-specific promoter system to up-regulate MHC
      class I in the skeletal muscles of young mice. These mice develop clinical,
      biochemical, histological, and immunological features very similar to human
      myositis. The disease is inflammatory, limited to skeletal muscles, self
      sustaining, more severe in females, and often accompanied by autoantibodies,
      including, in some mice, autoantibodies to histidyl-tRNA synthetase, the most
      common specificity found in the spontaneous human disease, anti-Jo-1. This model
      suggests that an autoimmune disease may unfold in a highly specific pattern as
      the consequence of an apparently nonspecific event-the sustained up-regulation of
      MHC class I in a tissue-and that the specificity of the autoantibodies derives
      not from the specificity of the stimulus, but from the context, location, and
      probably the duration of the stimulus. This model further suggests that the
      presumed order of events as an autoimmune disease develops needs to be
      reconsidered.

PMID- 10922074
TI  - Positron emission tomography provides molecular imaging of biological processes.
AB  - Diseases are biological processes, and molecular imaging with positron emission
      tomography (PET) is sensitive to and informative of these processes. This is
      illustrated by detection of biological abnormalities in neurological disorders
      with no computed tomography or MRI anatomic changes, as well as even before
      symptoms are expressed. PET whole body imaging in cancer provides the means to
      (i) identify early disease, (ii) differentiate benign from malignant lesions,
      (iii) examine all organs for metastases, and (iv) determine therapeutic
      effectiveness. Diagnostic accuracy of PET is 8-43% higher than conventional
      procedures and changes treatment in 20-40% of the patients, depending on the
      clinical question, in lung and colorectal cancers, melanoma, and lymphoma, with
      similar findings in breast, ovarian, head and neck, and renal cancers. A microPET
      scanner for mice, in concert with human PET systems, provides a novel technology
      for molecular imaging assays of metabolism and signal transduction to gene
      expression, from mice to patients: e.g., PET reporter gene assays are used to
      trace the location and temporal level of expression of therapeutic and endogenous
      genes. PET probes and drugs are being developed together-in low mass amounts, as
      molecular imaging probes to image the function of targets without disturbing
      them, and in mass amounts to modify the target's function as a drug. Molecular
      imaging by PET, optical technologies, magnetic resonance imaging, single photon
      emission tomography, and other technologies are assisting in moving research
      findings from in vitro biology to in vivo integrative mammalian biology of
      disease.

PMID- 10922075
TI  - Cloning and expression of a novel human antibody-antigen pair associated with
      Felty's syndrome.
AB  - An increasing number of studies suggest the importance of antibodies in the
      pathogenesis of most systemic and organ-specific autoimmune diseases, although
      there is considerable controversy over the precise role of the autoantibodies
      involved. In humans, a major obstacle to progress is the identification and
      cloning of the relevant autoantibodies and autoantigens. Here, an approach based
      on the sequential use of antibody phage display and antigen expression libraries
      is developed and applied to a donor suffering from rheumatoid arthritis (RA),
      splenomegaly, and peripheral destruction of neutrophils leading to neutropenia
      (Felty's syndrome). An antibody phage display library was constructed from bone
      marrow from the donor and a high-affinity human mAb, ANA15, selected by panning
      against fresh neutrophils and independently by panning against a fixed cell line.
      The antibody showed strong staining of neutrophils and a number of cell lines.
      Probing of a lambdagt11 expression library from an induced myelomonocytic cell
      line with the mAb ANA15 identified the eukaryotic elongation factor 1A-1 (eEF1A
      1) as a novel autoantigen. The specificity of ANA15 was confirmed by reactivity
      with both purified and recombinant eEF1A-1. Screening of a large panel of sera
      revealed that 66% of patients with Felty's syndrome had elevated levels of anti
      eEF1A-1 antibodies. The cloning of this antibody-antigen pair should permit
      rational evaluation of any pathogenicity resulting from the interaction and its
      significance in neutropenia.

PMID- 10922076
TI  - Pseudorabies virus expressing enhanced green fluorescent protein: A tool for in
      vitro electrophysiological analysis of transsynaptically labeled neurons in
      identified central nervous system circuits.
AB  - Physiological properties of central nervous system neurons infected with a
      pseudorabies virus were examined in vitro by using whole-cell patch-clamp
      techniques. A strain of pseudorabies virus (PRV 152) isogenic with the Bartha
      strain of PRV was constructed to express an enhanced green fluorescent protein
      (EGFP) from the human cytomegalovirus immediate early promoter. Unilateral PRV
      152 injections into the vitreous body of the hamster eye transsynaptically
      infected a restricted set of retinorecipient neurons including neurons in the
      hypothalamic suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL)
      of the thalamus. Retinorecipient SCN neurons were identified in tissue slices
      prepared for in vitro electrophysiological analysis by their expression of EGFP.
      At longer postinjection times, retinal ganglion cells in the contralateral eye
      also expressed EGFP, becoming infected after transsynaptic uptake and retrograde
      transport from infected retinorecipient neurons. Retinal ganglion cells that
      expressed EGFP were easily identified in retinal whole mounts viewed under
      epifluorescence. Whole-cell patch-clamp recordings revealed that the
      physiological properties of PRV 152-infected SCN neurons were within the range of
      properties observed in noninfected SCN neurons. Physiological properties of
      retinal ganglion cells also appeared normal. The results suggest that PRV 152 is
      a powerful tool for the transsynaptic labeling of neurons in defined central
      nervous system circuits that allows neurons to be identified in vitro by their
      expression of EGFP, analyzed electrophysiologically, and described in
      morphological detail.

PMID- 10922077
TI  - Spinophilin regulates the formation and function of dendritic spines.
AB  - Spinophilin, a protein that interacts with actin and protein phosphatase-1, is
      highly enriched in dendritic spines. Here, through the use of spinophilin
      knockout mice, we provide evidence that spinophilin modulates both glutamatergic
      synaptic transmission and dendritic morphology. The ability of protein
      phosphatase-1 to regulate the activity of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors was
      reduced in spinophilin knockout mice. Consistent with altered glutamatergic
      transmission, spinophilin-deficient mice showed reduced long-term depression and
      exhibited resistance to kainate-induced seizures and neuronal apoptosis. In
      addition, deletion of the spinophilin gene caused a marked increase in spine
      density during development in vivo as well as altered filopodial formation in
      cultured neurons. In conclusion, spinophilin appears to be required for the
      regulation of the properties of dendritic spines.

PMID- 10922078
TI  - Presenilin complexes with the C-terminal fragments of amyloid precursor protein
      at the sites of amyloid beta-protein generation.
AB  - An unusual intramembranous cleavage of the beta-amyloid precursor protein (APP)
      by gamma-secretase is the final step in the generation of amyloid beta-peptide
      (Abeta). Two conserved aspartates in transmembrane (TM) domains 6 and 7 of
      presenilin (PS) 1 are required for Abeta production by gamma-secretase. Here we
      report that the APP C-terminal fragments, C83 and C99, which are the direct
      substrates of gamma-secretase, can be coimmunoprecipitated with both PS1 and PS2.
      PS/C83 complexes were detected in cells expressing endogenous levels of PS. The
      complexes accumulate when gamma-secretase is inactivated either pharmacologically
      or by mutating the PS aspartates. PS1/C83 and PS1/C99 complexes were detected in
      Golgi-rich and trans-Golgi network-rich vesicle fractions. In contrast, complexes
      of PS1 with APP holoprotein, which is not the immediate substrate of gamma
      secretase, occurred earlier in endoplasmic reticulum-rich vesicles. The major
      portion of intracellular Abeta at steady state was found in the same Golgi/trans
      Golgi network-rich vesicles, and Abeta levels in these fractions were markedly
      reduced when either PS1 TM aspartate was mutated to alanine. Furthermore, de novo
      generation of Abeta in a cell-free microsomal reaction occurred specifically in
      these same vesicle fractions and was markedly inhibited by mutating either TM
      aspartate. Thus, PSs are complexed with the gamma-secretase substrates C83 and
      C99 in the subcellular locations where Abeta is generated, indicating that PSs
      are directly involved in the pathogenically critical intramembranous proteolysis
      of APP.

PMID- 10922079
TI  - Role of C-terminal domains of the G protein beta subunit in the activation of
      effectors.
AB  - The prenyl group on the G protein gamma subunit is an important determinant of
      protein-protein interactions between the betagamma dimer and its targets, such as
      alpha subunits, receptors, and effectors. In an effort to identify domains of the
      beta subunit important for the activation of effectors, we have prepared two
      types of mutants, one set in the domain suggested to form a hydrophobic prenyl
      binding pocket for the gamma subunit's prenyl group (prenyl pocket mutants) and
      the other set in a domain between Gly(306) and Gly(319) in the beta propeller,
      which undergoes a conformational change when the dimer binds to phosducin
      (conformational change mutants). Recombinant baculoviruses for each set of
      mutants were prepared, and the nine mutant beta subunits were overexpressed with
      either the gamma(2) subunit (modified with geranylgeranyl) or the gamma(2-L71S)
      subunit (gamma(2) with altered CAAX sequence and modified with farnesyl). The
      purified dimers were tested for their ability to couple Galpha(i1) to the A1
      adenosine receptor and to activate phospholipase C-beta or type II adenylyl
      cyclase. All dimers containing mutant beta subunits were indistinguishable from
      wild-type beta(1)gamma(2) or beta(1)gamma(2-L71S) in coupling the receptor to
      Galpha(i1). The prenyl pocket mutants expressed with gamma(2) were 10-fold less
      potent in activating phospholipase C-beta and adenylyl cyclase than
      beta(1)gamma(2) and had similar activities to beta(1)gamma(2-L71S). The
      conformational change mutants caused a 15- to 23-fold decrease in EC(50) values
      for activation of these two effectors. Overall, the results suggest that the
      sites in Gbeta identified by these mutants are very important in the activation
      of effectors. Furthermore, the nature of the prenyl group on Ggamma may play an
      important role in the conformational change leading to the activity of Gbetagamma
      on effectors.

PMID- 10922081
TI  - Etiology of interepidemic periods of mosquito-borne disease.
AB  - Dengue viruses and malaria protozoa are of increasing global concern in public
      health. The diseases caused by these pathogens often show regular seasonal
      patterns in incidence because of the sensitivity of their mosquito vectors to
      climate. Between years in endemic areas, however, there can be further
      significant variation in case numbers for which public health systems are
      generally unprepared. There is an acute need for reliable predictions of within
      year and between-year epidemic events. The prerequisite for developing any system
      of early warning is a detailed understanding of the factors involved in epidemic
      genesis. In this report we discuss the potential causes of the interepidemic
      periods in dengue hemorrhagic fever in Bangkok and of Plasmodium falciparum
      malaria in a highland area of western Kenya. The alternative causes are
      distinguished by a retrospective analysis of two unique and contemporaneous 33
      year time series of epidemiological and associated meteorological data recorded
      at these two sites. We conclude that intrinsic population dynamics offer the most
      parsimonious explanation for the observed interepidemic periods of disease in
      these locations.

PMID- 10922080
TI  - Interleukin-6 is an essential, corticotropin-releasing hormone-independent
      stimulator of the adrenal axis during immune system activation.
AB  - Glucocorticoids play a critical role in control of the cytokine response after
      immune challenge. Conversely, cytokines modulate glucocorticoid production by the
      hypothalamic-pituitary-adrenal axis. To define the potency and mechanism of
      interleukin-6 (IL-6) for augmentation of adrenal function, we exploited mice
      deficient in corticotropin-releasing hormone (CRH), IL-6, or both. Mice deficient
      in CRH action demonstrate severely impaired glucocorticoid production in response
      to psychological and metabolic challenge, but near normal responses to stressors
      that activate the immune system. In this paper, we demonstrate that IL-6 is
      essential for activation of the hypothalamic-pituitary-adrenal axis during
      immunological challenge in the absence of hypothalamic input from CRH. IL-6
      receptors are present on pituitary corticotrophs and adrenocortical cells,
      consistent with the ability of IL-6 to bypass CRH in augmentation of adrenal
      function. Plasma corticosterone levels after bacterial lipopolysaccharide
      injection in mice deficient in CRH or IL-6 were significantly lower than in wild
      type mice but significantly greater than in mice deficient in both CRH and IL-6.
      A second model of immune system activation using 2C11, an antibody to the T cell
      receptor, demonstrated a normal corticosterone response in mice deficient in CRH
      or IL-6, but a markedly decreased response in mice deficient in both CRH and IL
      6. Surprisingly, the relative contribution of IL-6 for modulation of the adrenal
      response to stress is greater in female than in male mice. This gender-specific
      difference in IL-6 action in mice suggests the utility of further analysis of IL
      6 in determining the female predominance seen in many human
      inflammatory/autoimmune diseases.

PMID- 10922082
TI  - A dynamic model of social network formation.
AB  - We consider a dynamic social network model in which agents play repeated games in
      pairings determined by a stochastically evolving social network. Individual
      agents begin to interact at random, with the interactions modeled as games. The
      game payoffs determine which interactions are reinforced, and the network
      structure emerges as a consequence of the dynamics of the agents' learning
      behavior. We study this in a variety of game-theoretic conditions and show that
      the behavior is complex and sometimes dissimilar to behavior in the absence of
      structural dynamics. We argue that modeling network structure as dynamic
      increases realism without rendering the problem of analysis intractable.

PMID- 10922084
TI  - EUS to detect evidence of pancreatic disease in patients with persistent or
      nonspecific dyspepsia.
AB  - BACKGROUND: Mild chronic pancreatitis is difficult to diagnose and the diagnosis
      is therefore not sought routinely in patients with dyspepsia. The aim of our
      study was to compare the prevalence of endosonographic pancreatic abnormalities
      in patients with dyspepsia and control subjects. METHODS: The number of
      endosonographic abnormalities was compared prospectively in patients with
      dyspepsia and control patients. Patients in whom there was any suspicion of
      pancreatic disease were analyzed separately. RESULTS: Between November 1998 and
      January 1999, 156 patients with dyspepsia were compared with 27 control patients.
      The groups were similar except that control patients were significantly older and
      more likely to be men. The mean number of endosonographic abnormalities was
      higher in dyspeptic patients than in control patients (mean number of
      abnormalities 3.3: 95% CI [2.9, 3.6] vs. 1.9: 95% CI [0.3, 1.7]). The strongest
      independent predictors of severe endosonographic abnormalities (defined as 5 or
      more abnormalities) were the presence of suspected pancreatic disease (odds ratio
      7.29: 95% CI [2.03, 26. 14]) and dyspepsia (odds ratio 7.21: 95% CI [1.99,
      26.26]). In the dyspepsia group, no clinical variables were significant
      predictors of severe abnormalities. However, most patients had nonspecific-type
      dyspepsia or persistent symptoms after therapeutic trials of acid suppression.
      CONCLUSIONS: Dyspepsia may be an atypical presentation of pancreatic disease in
      patients with persistent or nonspecific symptoms. Endosonography may be useful to
      screen for pancreatic disease in patients with persistent dyspepsia.

PMID- 10922085
TI  - Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate
      (Histoacryl) injection: long-term efficacy and safety.
AB  - BACKGROUND: The long-term efficacy and safety of the endoscopic injection of N
      butyl-2-cyanoacrylate (Histoacryl) were evaluated to define its role as the
      initial treatment for bleeding gastric varices. METHODS: Ninety patients with
      bleeding gastric varices underwent endoscopic injections of Histoacryl for
      hemostasis within a 6-year period. Histoacryl was injected intravariceally as a
      1:1 mixture with Lipiodol. Among the 90 patients, 5 had active bleeding and 85
      had recent bleeding. Most of the varices were large (F2 or F3, 85 cases). The
      most common locations were the fundus and the posterior wall of the proximal body
      (94.4%). After Histoacryl injection, patients were followed endoscopically with
      retreatment as necessary. RESULTS: The rate of hemostasis at 1 week was 94.4%.
      Recurrent bleeding occurred in 23.3% of the patients from 3 days to 16 months
      after the initial injection. Recurrent bleeding was stopped with reinjections of
      Histoacryl in 16.7% of the patients. The rate of definitive hemostasis was 93.3%
      (84 of 90). The treatment failure-related mortality rate was 2.2% (2 of 90). To
      date, 35 patients have died, mostly as a result of malignancy or liver failure,
      and 55 are still alive. The determining factor for long-term survival was the
      underlying disease leading to portal hypertension. There were few long-term
      complications except for Histoacryl cast extrusion-related mucosal defects.
      CONCLUSIONS: Endoscopic injection of Histoacryl is highly effective for the
      treatment of bleeding gastric varices, with rare complications both acutely and
      long term. This treatment modality is appropriate as the first choice for
      bleeding gastric varices.

PMID- 10922086
TI  - EUS-guided injection of cyanoacrylate for bleeding gastric varices.
AB  - BACKGROUND: Bleeding gastric varices is a highly fatal condition. Recurrent
      bleeding after hemostasis achieved by endoscopic methods is common, and
      obliteration of gastric varices is difficult to assess. Our aim was to
      investigate the use of endosonography (EUS) in monitoring cyanoacrylate injection
      to obliterate gastric varices. METHODS: Patients who presented with bleeding
      gastric varices were treated with bolus injection(s) of cyanoacrylate (0.5 mL
      cyanoacrylate mixed with 0.7 mL Lipiodol) until bleeding was controlled; 47
      patients received "on-demand" injection only in response to recurrent bleeding
      (on-demand group). Another group of 54 patients underwent biweekly EUS followed
      by repeated injection of cyanoacrylate (repeated-injection group) until all
      gastric varices were obliterated. The primary outcome was recurrent bleeding-free
      interval and survival rate. RESULTS: The two groups of patients were comparable
      demographically. Although the rates of early (</=48 hour) bleeding recurrence
      were similar with repeated or on-demand injection (7.4% versus 12.8%, p = 0.5),
      late recurrence of bleeding (>48 hour) was significantly reduced in the repeated
      injection group (18.5% versus 44.7%, p = 0.0053, odds ratio 0.28 (95% CI [0.12,
      0. 69]). Cumulative probability of recurrent bleeding-free interval was higher in
      the repeated-injection than the on-demand group (log-rank test, p = 0.0053).
      There was a numeric trend toward improved survival in the repeated-injection
      group. CONCLUSION: Gastric varices obliteration with cyanoacrylate under EUS
      monitoring reduces recurrent bleeding and may improve survival.

PMID- 10922087
TI  - Is prophylactic ciprofloxacin effective in delaying biliary stent blockage?
AB  - BACKGROUND: Late stent blockage is a major complication of endoscopic stent
      insertion for malignant obstructive jaundice. Stents block as a result of
      bacterial infection and biofilm formation. We report a randomized but unblinded
      study using an animal model to evaluate the effect of prophylactic ciprofloxacin,
      which selectively suppresses gram-negative bacteria, in an attempt to prolong
      stent patency. METHOD: Ten adult cats underwent surgical implantation of 5F
      polyethylene stents through common bile duct strictures created around the
      choledochotomy, with the tip of the stent left in the duodenum. Five animals
      received intravenous ciprofloxacin perioperatively and were then maintained on
      oral ciprofloxacin 25 mg twice daily. Control cats were not given antibiotics.
      The animals were sacrificed when signs of biliary obstruction or cholangitis
      persisted for more than 3 days or at the end of the 16-week study period. Stents
      were removed and examined for patency. In addition, the stents were cultured to
      recover the adherent bacteria. RESULTS: All control animals developed stent
      blockage within 4 weeks. Two ciprofloxacin-treated cats developed stent blockage
      at 21 and 42 days, respectively, whereas the other 3 cats had patent stents for
      the entire study period. There was a significant difference between the median
      stent patency of 112 days for the ciprofloxacin group versus 16 days for the
      control group (p < 0.02). Bacteriologic cultures showed that the bile and blocked
      stents from the control group had predominantly gram-negative bacteria, whereas
      the bile and stents of the ciprofloxacin group had gram-positive and anaerobic
      bacteria, with an absence of gram-negative bacteria (p < 0.01). CONCLUSION:
      Ciprofloxacin prophylaxis eliminates gram-negative bacterial infection in bile
      and minimizes sludge formation and may have a potential benefit in delaying stent
      blockage.

PMID- 10922088
TI  - Sphincter of oddi manometry: is it necessary to measure both biliary and
      pancreatic sphincter pressures?
AB  - BACKGROUND: Data are scant on the miss rate of sphincter of Oddi dysfunction if
      basal pressure in both biliary and pancreatic sphincter segments is not measured
      during manometry. METHODS: Motility tracings with basal pressure measurements of
      both sphincter segments were retrospectively analyzed. Basal sphincter pressure
      greater than 40 mm Hg was considered abnormal in either sphincter segment.
      RESULTS: The study population consisted of 73 subjects (64 women, 9 men; age 45.3
      +/- 1.6 yr). The basal pressures in the 2 sphincter segments were highly
      discordant (correlation coefficient = 0.2, p = 0.04). Basal pressures were normal
      in both segments in 19%, abnormal in both segments in 40%, and abnormal in 1
      segment but normal in the other in 41%. The negative predictive value of normal
      biliary sphincter pressure in excluding sphincter dysfunction was 0. 42; when the
      pancreatic sphincter pressure was normal, the negative predictive value was 0.58.
      The incidence of pancreatitis with dual duct manometry was comparable to the
      institutional experience with all sphincter studies. CONCLUSIONS: Although the
      clinical relevance of individually elevated sphincter pressures remains
      uncertain, there is significant discordance of basal pressures between the
      biliary and pancreatic sphincter segments. If only the biliary sphincter pressure
      were to be measured, one fourth of abnormal sphincter pressures would be missed.
      Therefore, if the first sphincter segment has a normal basal pressure, the other
      segment should also be evaluated.

PMID- 10922089
TI  - Endoscopic sphincterotomy for bile duct stones in patients 90 years of age and
      older.
AB  - BACKGROUND: Little information is available on the outcomes of endoscopic
      sphincterotomy for choledocholithiasis in patients of advanced age (>/=90 years).
      METHODS: Endoscopic sphincterotomy was performed for choledocholithiasis in 22
      patients aged 90 years or more (group A) and 381 aged 70 to 89 years (group B).
      Clinical features and early outcomes of endoscopic sphincterotomy were compared
      between the two groups. In group A, long-term results for a mean follow-up period
      of 33 months were assessed. RESULTS: Group A patients had a higher incidence of
      symptoms, acute cholangitis and concomitant diseases, as well as larger and more
      numerous gallstones than did group B patients. Endoscopic sphincterotomy was
      technically successful in 100% of group A patients and 98% of group B patients.
      The rate of early complications was low in both groups: 5% in group A and 7% in
      group B. No deaths related to endoscopic retrograde cholangiopancreatography
      occurred in group A patients. Complete stone clearance was achieved in 86% of
      group A patients and 95% of group B patients. Group A required an emergency
      procedure, general anesthesia, multiple sessions, mechanical lithotripsy, and
      permanent biliary stent placement more frequently than group B. Late
      complications occurred in 5% of group A patients. CONCLUSION: Endoscopic
      sphincterotomy is safe and effective for the treatment of choledocholithiasis in
      patients 90 years of age or older. Biliary stent placement is a reasonable
      alternative treatment when stones prove to be difficult to extract.

PMID- 10922091
TI  - Practice patterns for surveillance of Barrett's esophagus in the united states.
AB  - BACKGROUND: Endoscopic surveillance of Barrett's esophagus is recommended to
      detect dysplasia or cancer at an early and potentially treatable stage. However,
      little is known about the clinical practice patterns for endoscopic surveillance
      in the United States. METHODS: A questionnaire regarding surveillance intervals,
      techniques and management approaches for patients with Barrett's esophagus was
      mailed to 1000 randomly selected members of the Clinical Practice Section of the
      American Gastroenterological Association. RESULTS: The response rate was 455 of
      1000 (45%). Not all respondents answered all questions. Seventy-nine percent of
      respondents were in community practices, and 21% were in academic practices.
      Nearly all (96%) performed endoscopic surveillance, but it was practiced more
      commonly in the community (334 of 341 [98%]) than in the academic setting (83 of
      93 [89%], p < 0.001). For patients without dysplasia, endoscopic surveillance was
      most commonly performed every 2 years (264 of 415 [64%]). Patients with low-grade
      dysplasia usually had surveillance endoscopy at 6-month intervals (215 of 413
      [52%]), whereas those with high-grade dysplasia most commonly had endoscopy every
      3 months (201 of 404 [50%]). These surveillance patterns did not differ between
      the academic and community groups. Random biopsies were performed by 93 of 403
      (23%), 4-quadrant biopsies by 310 (77%). Most physicians (83%) used standard
      capacity forceps. Brush cytology was done uncommonly (69 of 414 [17%]). The most
      common indications for esophagectomy were high-grade dysplasia by 82% and cancer
      by 83%. Ablation therapy was performed for Barrett's esophagus without dysplasia
      by 3.5%, Barrett's with dysplasia by 20%, and cancer by 8%. CONCLUSIONS:
      Surveillance for Barrett's esophagus is widely practiced in the United States but
      there is considerable variation in interval and technique. A clearer consensus on
      endoscopic surveillance is warranted to optimize care of patients with Barrett's
      esophagus.

PMID- 10922090
TI  - Bispectral index monitoring of sedation during endoscopy.
AB  - BACKGROUND: No objective measure of the level of sedation is universally
      accepted. However, bispectral index monitoring is currently used to objectively
      measure sedation levels in several clinical settings. This study compares the
      temporal relationship of bispectral index levels versus the Observer's Assessment
      of Alertness/Sedation (OAA/S) scale for sedation during endoscopy and proposes a
      functional bispectral index range for endoscopic procedures. METHODS: Fifty
      consecutive adults undergoing endoscopic retrograde cholangiopancreatography,
      colonoscopy, or esophagogastroduodenoscopy by a single endoscopist were studied.
      Intravenous sedation was achieved with diazepam and meperidine. Bispectral index
      levels (0 to 100) and OAA/S scores (1 to 5) were recorded every 3 minutes by a
      single trained observer. RESULTS: There were significant temporal correlations
      between bispectral index levels and OAA/S scores (r = 0.59, p < 0.0001).
      Bispectral index levels and OAA/S scores corresponded with the need for
      additional sedation as determined clinically by the endoscopist. An OAA/S score
      of 3 corresponded to a bispectral index level of 81.49 +/- 9.78. CONCLUSIONS:
      Bispectral index monitoring temporally correlates with the OAA/S scale and
      therefore provides an objective measure of sedation during endoscopy. This
      preliminary, observational study suggests that a bispectral index level near 82
      corresponds with sufficient and functional sedation levels for endoscopy.

PMID- 10922092
TI  - Timing and scheduling of endoscopic procedures.
AB  - BACKGROUND: The aim of the present analysis is to compare the costs associated
      with different schemes of scheduling tests and to develop recommendations
      concerning the most cost-effective means for timing individual endoscopic
      procedures. METHODS: The diagnostic costs of three competing strategies to
      schedule various radiologic and endoscopic procedures in patients with jaundice
      or gastrointestinal hemorrhage are compared by computer models using a Monte
      Carlo simulation. In strategy 1, the evaluation is started with the most
      promising procedure and proceeds with the next most promising procedure in case
      of a normal finding. In strategy 2, physicians adhere to a rigid sequence of
      diagnostic tests that starts with the least expensive procedure and advances
      through progressively more expensive procedures. In strategy 3, all promising
      tests are scheduled at the onset without waiting for test results to decide in
      favor or against individual procedures. In the Monte Carlo simulation, two
      hypothetical populations of 5000 inpatients or outpatients are subjected to each
      strategy. RESULTS: Unless one particular diagnosis is suspected with a high a
      priori probability, a rigid sequence of advancing from less to more expensive and
      invasive procedures provides the cheapest diagnostic strategy. In case of limited
      access to endoscopy and long waiting times, the cheapest work-up may include
      simultaneous scheduling of complementary procedures without waiting for
      intermediate test results. Strategy 1 of starting with the most promising test
      procedure becomes the least expensive option, if the prior probability assigned
      to the most likely diagnosis exceeds a threshold between 40% and 70%, depending
      on the type of test needed to make the diagnosis. CONCLUSIONS: An expeditious
      diagnostic evaluation or an evaluation that is guided primarily by medical
      considerations is more likely to result in low healthcare costs.

PMID- 10922093
TI  - Does open access endoscopy close the door to an adequately informed patient?
AB  - BACKGROUND: The use of open access endoscopy is increasing. Its effect on the
      adequacy of patient informed consent, procedure acceptance and the impact on
      subsequent communication/transfer of procedure results to the patient have not
      been evaluated. The aim of our study was to compare the extent of preknowledge of
      procedures and test explanation, patient medical complexity, information transfer
      and overall patient satisfaction between a patient group referred for outpatient
      open access endoscopy versus a patient group from a gastrointestinal (GI)
      subspecialty clinic. METHODS: Information was obtained from all patients
      presenting for outpatient upper and lower endoscopy by using a 1-page
      questionnaire. Patients from the two groups who had an outpatient upper/lower
      endoscopic procedure were contacted by phone after the procedure to obtain
      information with a standardized questionnaire. RESULTS: The open access patients
      reported receiving significantly less information to help them identify the
      procedure (p < 0.01) and less explanation concerning the nature of the procedure
      than the group of patients referred from the subspecialty clinic (p < 0.005).
      There was no difference between the two groups in satisfaction scores for
      examinations performed under conscious sedation. For flexible sigmoidoscopy
      without sedation, however, the GI clinic patient group were more satisfied with
      their procedure. The majority of patients, regardless of access, were more likely
      to receive endoscopic results from a gastroenterologist than the referring
      physician. Furthermore, the patients in the GI clinic group who underwent
      colonoscopy felt significantly better at follow-up. CONCLUSIONS: Patients
      undergoing open access procedures are less likely to be properly informed about
      their endoscopic procedure. Our results indicate that with open access endoscopy,
      a defined mechanism needs to be in place for communication of endoscopic results
      to the patient.

PMID- 10922095
TI  - Low frequency of bacteremia after endoscopic mucosal resection.
AB  - BACKGROUND: Endoscopic mucosal resection has become a popular alternative for the
      treatment of early-stage neoplasia of the gastrointestinal tract. However, there
      are still no data on the frequency of bacteremia associated with this form of
      treatment. METHODS: We conducted a prospective study of 21 men and 17 women
      undergoing endoscopic mucosal resection with a cap-fitted panendoscope for upper
      gastrointestinal lesions. Blood cultures were performed before, 10 minutes after,
      and 4 hours after the procedure for both aerobic and anaerobic bacteria. RESULTS:
      Blood culture at baseline was negative in all the patients. Two of 38 patients
      (5.3 %) had positive blood culture at 10 minutes after the procedure. The
      isolated microorganisms were Streptococcus salivarius and Corynebacterium
      species. All patients had negative blood cultures 4 hours later. None of these 38
      patients had any symptoms or signs associated with infection. CONCLUSIONS:
      Bacteremia associated with endoscopic mucosal resection is infrequent and
      transient.

PMID- 10922094
TI  - Prospective, randomized, single-blind comparison of two preparations for
      screening flexible sigmoidoscopy.
AB  - BACKGROUND: The best and most cost-effective bowel cleansing regimen for patients
      undergoing flexible sigmoidoscopy is not known. The aim of this study was to
      compare patient tolerance, quality of preparation, and cost of 2 bowel cleansing
      regimens for flexible sigmoidoscopy. METHODS: Two hundred fifty consecutive
      patients referred for screening flexible sigmoidoscopy were randomized to receive
      an oral preparation (45 mL oral sodium phosphate and 10 mg bisacodyl) or an enema
      preparation (2 Fleet enemas and 10 mg bisacodyl). Tolerance of the preparation
      was graded as easy, tolerable, slightly difficult, extremely difficult, or
      intolerable. The endoscopist was blinded to which preparation the patient
      received and graded the quality of the preparation as poor, fair, good, or
      excellent. Cost was calculated by adding the cost of the medications and the cost
      for the nursing time required to prepare the patient for endoscopy. RESULTS:
      Patients in the oral preparation group were more likely to grade the preparation
      as easy or tolerable when compared with the enema group (96.8% vs. 56.4%, p <
      0.001). The endoscopist graded the quality of the preparation as good or
      excellent in 86.5% of the patients in the oral preparation group compared with
      57.3% in the enema group (p < 0.001). In the oral preparation group, the mean
      nursing time (34.6 vs. 65.3 minutes, p < 0.001) and cost ($16.39 vs. $31.13, p <
      0.001) were significantly less than in the enema group. CONCLUSIONS: An oral
      sodium phosphate preparation results in a superior quality endoscopic examination
      that is better tolerated and more cost-effective than enemas in patients
      undergoing screening flexible sigmoidoscopy.

PMID- 10922096
TI  - Endoscopic treatment for esophageal varices: will there be a place for
      sclerotherapy during the forthcoming era of ligation?

PMID- 10922097
TI  - Primary pneumatosis cystoides intestinalis.

PMID- 10922098
TI  - Pseudomembranous colitis.

PMID- 10922099
TI  - Esophageal graft versus host disease.

PMID- 10922100
TI  - Pancreatic intraductal papillary mucin-producing tumor.

PMID- 10922101
TI  - The measurement of forces exerted during colonoscopy.
AB  - BACKGROUND: The widely varying forces used at colonoscopy have not been measured.
      An electronic device was designed to measure the forces exerted by the clinician
      on the endoscope during colonoscopy. METHODS: The device featured a handle
      designed in the shape of a hinged split cylinder that could be locked around the
      endoscope but readily moved up and down the insertion tube as the colonoscopy
      proceeded. This cylinder contained strain-gauges arranged so that the forces
      transmitted could be accurately measured. The device recorded the torque forces
      in addition to the push and pull forces exerted during diagnostic colonoscopy.
      RESULTS: In a series of 21 colonoscopies in 20 patients: peak pushing force = 4.4
      kg, pulling force = -1.8 kg, anti-clockwise torque = 1.0 Newton meters, clockwise
      torque = 0.8 Newton meters. Percentage time force greater than 1 kg = 5%. Peak
      anal insertion force = 1.8 kg. CONCLUSIONS: These measurements represent the
      first accurate measurements of the forces exerted during colonoscopy. Reducing
      the force during colonoscopy is likely to diminish pain and reduce the risk of
      perforation. A knowledge of these forces may also help with the design of new
      instruments and models for teaching or research.

PMID- 10922102
TI  - Hemoglobin content in intramucosal gastric carcinoma as a marker of histologic
      differentiation: a clinical application of quantitative electronic endoscopy.
AB  - BACKGROUND: It has been suggested that the endoscopic color of intramucosal
      gastric carcinoma is correlated with mucosal vascularity within the carcinomatous
      tissue. The development of electronic endoscopy has made it possible to
      quantitatively measure the mucosal hemoglobin volume, using a hemoglobin index.
      The aims of the present study were to investigate whether this hemoglobin index
      is useful for evaluating the change in color of early gastric carcinoma and to
      verify the diagnostic value of this index for distinguishing between histologic
      degrees of differentiation. METHODS: The ratios of the hemoglobin index of
      cancerous and non-cancerous mucosa for 26 differentiated and 18 undifferentiated
      intramucosal gastric carcinomas were determined from electronic endoscopic
      imaging data. RESULTS: The mean ratio of the hemoglobin index of cancerous and
      non-cancerous mucosa in the differentiated gastric carcinomas was higher than it
      was in the undifferentiated carcinomas (1.23: 95% CI [1.15, 1.31] versus 0.84:
      95% CI [0.81, 0. 88]). The sensitivity and specificity for discriminating
      undifferentiated from differentiated carcinoma were 100% and 85%, respectively.
      CONCLUSION: Measurement of mucosal hemoglobin volume (hemoglobin index) is useful
      for evaluating the endoscopic color of early gastric carcinoma quantitatively and
      may be helpful in distinguishing differentiated from undifferentiated carcinoma.

PMID- 10922103
TI  - Double-catheter method to prevent dislodgement during percutaneous transhepatic
      cholangioscopy.
AB  - BACKGROUND: We evaluated the utility of the double-catheter method to establish
      the track for percutaneous transhepatic cholangioscopy (PTCS). METHODS:
      Dilatation of the percutaneous transhepatic track to 16F for PTCS was attempted
      in 105 patients. The results were prospectively analyzed. Using the single
      catheter method (n = 22), a 16F PTCS catheter was replaced without the inner
      catheter. Using the double-catheter method (n = 83), a 7F catheter with a balloon
      tip was inserted through a 16F PTCS catheter. The balloon was located distal to
      the major duodenal papilla. The double-catheter method was further subclassified
      as follows: Method 2A (n = 62), the tip of the outer catheter (16F) was not
      advanced through biliary stenoses; Method 2B (n = 21), the catheter was advanced
      through biliary stenoses. RESULTS: In the patients treated by the double-catheter
      method, dislodgement of the catheter did not occur, whereas the single-catheter
      became dislodged in 18% (p < 0.0005). The morbidity of method 2A (0%) was less
      than that of method 2B (14%) (p < 0.005). CONCLUSION: The double-catheter method
      prevents dislodgement of the PTCS catheter. The outer catheter should not be
      advanced to the biliary stenosis.

PMID- 10922104
TI  - Gastroenterologist-administered propofol for therapeutic upper endoscopy with
      graphic assessment of respiratory activity: a case series.
AB  - BACKGROUND: Traditional methods of sedation and analgesia for advanced endoscopic
      procedures can be inadequate and frequently prolong recovery room observation.
      Propofol is a rapidly acting agent that produces an excellent hypnotic state, but
      its use is typically limited to anesthesiologist-assisted cases because of the
      inadequacy of current monitoring standards to reliably detect early stages of
      respiratory depression. METHODS: Ten patients undergoing advanced upper
      endoscopic procedures (endoscopic retrograde cholangiopancreatography, endoscopic
      ultrasound, esophageal stent placement) received a propofol infusion under the
      control of a second qualified gastroenterologist with advanced cardiac life
      support skills. Graphic assessment of respiratory activity was made by using a
      sidestream carbon dioxide detecting cannula. Patient satisfaction was measured
      with a 100 mm visual analog scale. Recovery scores were measured by standardized
      scoring of discharge criteria. RESULTS: Monitoring with graphic assessment of
      respiratory activity detected early phases of respiratory depression, resulting
      in a timely decrease in the propofol infusion without significant hypoxemia,
      hypercapnia, hypotension, or arrhythmias. Satisfaction scores were extremely high
      (median score 92 of 100) and 9 of 10 patients met discharge criteria at 15
      minutes after discontinuation of the propofol infusion. CONCLUSIONS: With the use
      of monitoring by graphic assessment of respiratory activity, propofol infusion by
      a second qualified gastroenterologist for prolonged upper endoscopic procedures
      is safe and results in high levels of patient satisfaction with rapid recovery
      times.

PMID- 10922105
TI  - Lymphangioma of large intestine: report of ten cases with endoscopic and
      pathologic correlation.
AB  - BACKGROUND: Lymphangioma of the intestinal tracts is extremely rare and usually
      presents as a sessile or pedunculated polyp. The cause of these gross morphologic
      differences is unknown. The aim of this study was to investigate the
      characteristic histopathology of the colonic lymphangiomas in comparison with
      their endoscopic findings. METHODS: Ten colonic lymphangiomas, diagnosed and
      resected endoscopically between 1992 and 1999, were microscopically examined and
      immunohistochemically stained with CD31, CD34, Factor VIII-related antigen, and
      smooth muscle actin. RESULTS: The characteristic endoscopic finding was a
      transparent, fluctuating sessile (7 cases) or pedunculated (3 cases) polypoid
      mass with the color of normal colonic mucosa. Proliferative and dilated lymphatic
      tumor vessels were found in the colonic mucosa as well as in the submucosa in
      seven cases. In three pedunculated lymphangiomas, dilated lymphatics were
      exclusively restricted to the submucosa. The endothelial lining cells stained
      positively for both CD31 and Factor VIII-related antigen in all 10 cases tested,
      but most cases were negative for CD34. CONCLUSION: A pedicle does not exclude the
      endoscopic diagnosis of lymphangioma and there is a close correlation between its
      presence and histologic submucosal localization of dilated lymphatic vessels.

PMID- 10922107
TI  - Santorinicele and recurrent acute pancreatitis in pancreas divisum: diagnosis
      with dynamic secretin-stimulated magnetic resonance pancreatography and
      endoscopic treatment.

PMID- 10922106
TI  - Self-expandable metal coil stents in the treatment of benign esophageal
      strictures refractory to conventional therapy: a case series.
AB  - BACKGROUND: Benign, refractory esophageal strictures are an important therapeutic
      challenge. Metallic self-expandable stents developed to treat malignant
      strictures have occasionally been used in the treatment of benign stenoses. This
      is a report of the use of 14 esophageal metallic stents in 10 patients with
      severe benign strictures. METHODS: Ten patients with peptic, post-surgical, or
      post-radiation esophageal strictures were treated with metallic stents. All
      patients had previously been treated, unsuccessfully, by endoscopic dilatation.
      Their strictures, although benign, gave rise to the same problems as malignant
      ones. RESULTS: In all patients, marked improvement of dysphagia was achieved with
      the use of metallic stents. They were inserted without early complications except
      for chest pain in one patient. Late complications were proximal and distal
      migration (in three patients) and a proximal stricture in one other patient. The
      best results were achieved in post-radiation strictures. CONCLUSIONS: Metallic
      stents can be considered as a therapeutic alternative in selected patients with
      severe benign esophageal strictures refractory to conventional treatment.

PMID- 10922109
TI  - Malignant peritoneal mesothelioma: mucosal duodenal involvement and endoscopic
      diagnosis.

PMID- 10922108
TI  - Visceral fistula as a complication of endoscopic treatment of esophageal and
      gastric varices using isobutyl-2-cyanoacrylate: report of two cases.

PMID- 10922110
TI  - Endoscopic manifestations of metastatic hepatocellular carcinoma to the stomach:
      report of two cases.

PMID- 10922111
TI  - Endoscopic biliary stent placement for treatment of gallbladder perforation due
      to blunt abdominal injury.

PMID- 10922113
TI  - A novel approach to radiation-induced post-cricoid esophageal stricture: the
      "Laryngeal Jack" to facilitate dilatation.

PMID- 10922112
TI  - Magnetic resonance cholangiopancreatography documents bile leak site after
      cholecystectomy in patients with aberrant right hepatic duct where ERCP fails.

PMID- 10922114
TI  - Endoscopic sclerotherapy for esophageal hemangioma.

PMID- 10922116
TI  - Epstein-Barr virus-related gastric pseudolymphoma in infectious mononucleosis.

PMID- 10922115
TI  - Endoscopic appearance of the GI lesions associated with Sweet's syndrome.

PMID- 10922117
TI  - Carotid-esophageal fistula treated with balloon tamponade and surgery.

PMID- 10922118
TI  - The diagnosis of chronic pancreatitis.

PMID- 10922119
TI  - Glue for gastric varices: some sticky issues.

PMID- 10922121
TI  - Comment

PMID- 10922120
TI  - Hands-on ERCP training workshops: an experience with teaching endoscopists in
      China.

PMID- 10922122
TI  - Complex decisions after local (endoscopic) resection of early rectal cancer:
      opening Pandora's box of staging and treatment options.

PMID- 10922123
TI  - Response

PMID- 10922125
TI  - Response

PMID- 10922124
TI  - Colonoscopy in ischemic enterocolitis.

PMID- 10922126
TI  - Yields from percutaneous transhepatic cholangioscopic biopsies.

PMID- 10922127
TI  - Response

PMID- 10922129
TI  - Comparison of physical activity in adolescents with cystic fibrosis versus age
      matched controls.
AB  - The aims of this study were to compare self-reported vigorous physical activity
      and participation in sports among adolescents with cystic fibrosis (CF) to those
      of age matched peers from the general population, and to determine which CF
      patient characteristics are associated with regular physical activity. One
      hundred and sixteen of 141 (82%) adolescents aged 12-19 years identified through
      North Carolina CF Care Center registries confidentially completed a self
      administered questionnaire (the CDC's Youth Risk Behavior Survey) addressing
      health-compromising and health-enhancing behaviors, including physical activity.
      They were age- and gender-matched to adolescents from North Carolina schools who
      completed the same survey. Adolescents with CF did not differ significantly from
      their matched peers with regard to participating three or more times a week in
      activities that "make you sweat or breathe hard" (63% vs. 67%, P = 0.37),
      physical education class (59% vs. 61%, P = 0.81), or team sports (52% vs. 61%, P
      = 0.10). For all categories of activity, participation declined among adolescents
      aged 17 years or older. After adjusting for gender and health status, early (14
      years or younger) and middle (15-16 years) adolescents were more likely to
      participate in all three types of activity than older adolescents with CF. Like
      their peers in the general population, adolescents aged 17 and older are much
      less likely to report regular physical activity, or participation in physical
      education class or in team sports. Healthcare providers should be aware of this
      decline in activity in late adolescence and should consider efforts to maintain
      physical activity among older teenagers and young adults.

PMID- 10922128
TI  - Elevation of nitrotyrosine and nitrate concentrations in cystic fibrosis sputum.
AB  - Nitric oxide (NO) is increased in the exhaled air of some patients with
      inflammatory lung disorders, but not in others. NO may combine with superoxide to
      form peroxynitrite, which lowers NO gas concentrations, increases formation of
      nitrate, and increases nitration of tyrosine residues on proteins. We
      hypothesized that superoxide released from neutrophils in the lower respiratory
      tract of cystic fibrosis (CF) results in increased nitrate and nitrotyrosine
      levels in sputum. In order to test this hypothesis, exhaled NO was collected from
      5 stable adult CF subjects and from 5 nonsmoking normal controls. Consistent with
      previous reports, exhaled NO concentrations were not increased in CF exhaled air
      (22.6 +/- 1.5 ppb vs. 28.6 +/- 1.5 ppb in normals, P > 0.05). Sputum was
      collected from 9 adult CF subjects and the same 5 normal controls and evaluated
      for nitrite, nitrate, and nitrotyrosine. Nitrate and nitrotyrosine levels, but
      not nitrite, were significantly elevated in CF. Recently, myeloperoxidase has
      also been implicated as a mechanism of nitrotyrosine formation. Therefore,
      myeloperoxidase was measured and found to be elevated in the CF sputum (64.2 +/-
      35.9 vs. 0.73 +/- 0.16 U/mL, P < 0.001), and was found to correlate with
      concentrations of nitrotyrosine (r = 0.87, P < 0.05). However, in vitro studies
      with myeloperoxidase and murine lung epithelial cells did not demonstrate a
      reduction of NO gas with nitrotyrosine or an increase in nitrate formation. These
      data demonstrate that nitrate and nitrotyrosine are elevated in the sputa of CF
      subjects and suggest increased production of NO in the lower respiratory tract of
      CF patients, despite the relatively low exhaled NO levels. Pediatr Pulmonol.
      2000; 30:79-85. Published 2000 Wiley-Liss, Inc.

PMID- 10922130
TI  - Long-term effects of prednisolone in the acute phase of bronchiolitis caused by
      respiratory syncytial virus.
AB  - Follow-up studies have demonstrated that bronchiolitis caused by respiratory
      syncytial virus (RSV) is strongly associated with wheezing in the ensuing years.
      During the acute infection the immune response may induce long-lasting
      detrimental effects, thereby contributing to post-bronchiolitis wheezing (PBW).
      Therefore, immune-modulating drugs like corticosteroids, administered in the
      acute phase of RSV bronchiolitis, may prevent PBW and asthma. To evaluate this,
      we performed a controlled prospective follow-up study after a randomized double
      blind placebo-controlled intervention in the acute phase with oral prednisolone.
      Fifty-four patients under 2 years of age and hospitalized for RSV bronchiolitis
      between 1992 and 1995 were randomly assigned to prednisolone 1 mg/kg/day for 7
      days or placebo. At the mean age of 5 years, 47 patients had completed their
      follow-up. Patients were divided into four groups: no wheezing, transient
      wheezing (wheezing during the first year of life); persistent wheezing (wheezing
      during the first year of life and asthma at the age of 5); and late-onset
      wheezing (no wheezing during the first year of life but asthma at the age of 5).
      Prevalence of wheezing and asthma were investigated through an interview by
      telephone, using a standardized questionnaire. We found no significant
      differences between the prednisolone- and the placebo-treated group in the number
      of patients with transient wheezing (8% vs. 17%), persistent wheezing (42% vs.
      31%), or late-onset wheezing (17% vs. 13%). We conclude that oral prednisolone
      during the acute phase of RSV bronchiolitis is not effective in preventing PBW or
      asthma at the mean age of 5 years. Pediatr Pulmonol. 2000; 30: 92-96.

PMID- 10922131
TI  - Salmeterol/fluticasone propionate (50/100 microg) in combination in a Diskus
      inhaler (Seretide) is effective and safe in children with asthma.
AB  - The aim of this study was to compare the efficacy and safety in children of
      salmeterol (50 microg twice daily) plus fluticasone propionate (100 microg twice
      daily) when delivered together via a single Diskus inhaler (Seretide; combination
      therapy) or concurrently using two separate Diskus inhalers (concurrent therapy).
      In a multicenter, randomized, double-blind, double-dummy, parallel-group study,
      257 children with reversible airways obstruction who remained symptomatic on
      inhaled corticosteroids (200-500 microg daily) alone were randomized to
      combination or concurrent therapy for 12 weeks. Efficacy was assessed by
      measuring daily peak expiratory flow (PEF), symptom scores, and rescue salbutamol
      use. In addition, lung function tests were performed at each clinic visit. Safety
      assessments included monitoring of adverse events and morning serum cortisol
      concentrations. The primary efficacy parameter (mean morning PEF) increased
      during treatment in both groups; adjusted mean changes were 33 and 28 L/min for
      the combination and concurrent therapies, respectively. The 90% confidence
      interval for the difference in mean morning PEF between treatment groups was
      within the +15 L/min criterion for clinical equivalence. Similarly, there were
      improvements in pulmonary function, symptom score, and rescue salbutamol use
      during treatment in both groups, with no significant differences between the
      combination and concurrent therapy groups for any of these secondary efficacy
      parameters. Both treatment regimens were well-tolerated and had comparable
      adverse event profiles. Mean morning serum cortisol levels increased similarly in
      both groups during the study. In conclusion, salmeterol and fluticasone
      propionate therapy given as a new combination product is as safe and effective in
      children with asthma as the same drugs given concurrently via separate inhalers.

PMID- 10922132
TI  - Interaction between lung surfactant and nitric oxide production by alveolar
      macrophages stimulated by group B streptococci.
AB  - The major etiologic agent in neonatal pneumonia and meningitis is group B
      streptococci (GBS). Nitric oxide (NO) production by alveolar macrophages (AM) in
      response to Gram-positive bacteria such as GBS and the effect of surfactant on
      this production have received little attention. We studied production of NO by
      GBS-stimulated AM using the Griess reaction, the effect of lung surfactant on
      this NO production, and the possible lipid peroxidation (LPO) of surfactant
      caused by NO. The LPO test was used to measure surfactant peroxidation. Heat
      killed and live GBS were found to stimulate NO production by rat alveolar
      macrophages, and the presence of interferon gamma (IFN-gamma) increased this
      stimulation in a synergistic manner. Curosurf(R), the natural surfactant used in
      our study, significantly reduced NO production in various sets of experiments.
      Lipid peroxidation of surfactant was noted when NO was produced by stimulated AM,
      a phenomenon that could be suppressed by NG-monomethyl L-arginine (L-NMMA), the
      inhibitor of NO synthase. In the lung of GBS-infected neonates, nitric oxide
      produced by AM might contribute to the destruction of surfactant caused by
      inflammatory cells. Pediatr Pulmonol. 2000; 30:106- 113.

PMID- 10922133
TI  - Effect of perfluorochemical liquid ventilation on cardiac output and blood
      pressure variability in neonatal piglets with respiratory insufficiency.
AB  - Respiration and mechanical ventilation induce cyclic variation in cardiac output
      and blood pressure. We examined these phasic hemodynamic influences of mechanical
      ventilation during gas ventilation and partial and tidal liquid ventilation in 7
      anesthetized and paralyzed young piglets (body weight, 3.0-4.9 kg) made
      respiratory-insufficient by repeated saline lung lavage. Nonlinear regression
      analysis of cardiovascular parameters vs. time was done to quantify respiratory
      induced fluctuations in hemodynamic variables. The amplitude of oscillations was
      expressed as a percentage of the mean hemodynamic variable during the study
      period, and was called the relative oscillation amplitude. The relative
      oscillation amplitude of left ventricular stroke volume, left ventricular output,
      systemic arterial pressure, and systemic perfusion pressure was significantly
      larger (at least twofold) during tidal liquid ventilation compared to partial
      liquid ventilation. No such differences were observed between gas and partial
      liquid ventilation at comparable gas ventilator settings. We conclude that in
      this animal model, within-breath modulation of left ventricular output, systemic
      blood pressure, and perfusion pressure was significantly increased during tidal
      liquid ventilation as compared to partial liquid ventilation.

PMID- 10922134
TI  - Long-term outcome of surgically treated acquired subglottic stenosis in infancy.
AB  - There is little information about the long-term outcome of infants with acquired
      severe subglottic stenosis (SGS) who require surgical intervention. We
      retrospectively identified infants with acquired subglottic stenosis who required
      anterior cricoid split (ACS) or tracheostomy for primary airway management; some
      of these children later required laryngotracheoplasty (LTP). All children were
      treated at our hospital from 1989-1997. During follow-up, we assessed patients
      for persistent symptoms (stridor at rest, exercise limitation, difficulty with
      respiratory tract infections, recurrent croup, and voice alteration), and we
      measured lung function when possible. We identified 34 infants with acquired SGS:
      13 treated primarily with tracheostomy, and 21 with ACS. Nine patients could not
      be extubated following ACS and required tracheostomy, while the 12 who were
      extubated were followed up at a mean time of 76 months postoperatively; 3 had
      moderate stridor at rest, 1 moderate exercise limitation, and none had recurrent
      croup. Four of 5 who had lung function measured had moderately severe
      extrathoracic airflow limitation. From the tracheostomy group (n = 13) and the
      failed ACS group (n = 9), 2 patients were decannulated without further surgery,
      17 underwent LTP, and 2 have LTP planned. Fifteen of the 17 patients who had LTP
      have been decannulated. Follow-up, at a mean time of 58 months postoperatively,
      showed none with stridor at rest, 3 with moderate exercise limitation, none with
      recurrent croup, and 2 with moderate voice alteration. All 5 patients who had
      lung function measured had airflow limitation, 1 being severe. In conclusion, ACS
      facilitates extubation in selected patients with severe, acquired SGS of infancy,
      and the long-term outcome of patients successfully extubated is excellent.
      Failure of ACS invariably means tracheostomy, and subglottic repair by LTP is
      associated with a good long-term outcome.

PMID- 10922135
TI  - Novel pathways in the pathogenesis of respiratory syncytial virus disease.
AB  - Respiratory syncytial virus (RSV) is a leading cause of severe respiratory
      infections in infants and children. Extensive research in past decades has
      expanded our knowledge regarding the specific mechanisms involved in the
      pathogenesis of RSV bronchiolitis and subsequent chronic obstructive airway
      disease. Studies of RSV infection are performed in humans, cell culture models,
      and animal models, each with their own specific limitations. A recently developed
      murine model in which pulmonary dysfunction can be monitored and quantified
      appears to add a powerful tool for the study of specific pathogenic mechanisms of
      experimental RSV infections. Both immunologic and nonimmunologic factors have
      been implicated in the pathogenesis of RSV-induced diseases. Recently, a
      hypothesis that RSV bronchiolitis may be the result of production of Th2-type
      cytokines has become popular. There are, however, studies in human infants with
      RSV as well as in RSV-infected mice that suggest this theory is incorrect, or at
      least an oversimplification. There is compelling evidence that cells producing
      interferon gamma may contribute to RSV-induced wheezing, possibly through
      induction of leukotriene release. Among the nonimmunologic factors, pulmonary
      surfactant has recently attracted attention, especially because of the
      therapeutic implications for infants with severe bronchiolitis. A better
      understanding of the pathogenesis of RSV-induced diseases will be of considerable
      help in developing specific therapeutic strategies and in vaccine development.

PMID- 10922136
TI  - Time to think again: cystic fibrosis is not an "all or none" disease.

PMID- 10922137
TI  - Pigeon breeder's lung in childhood: varied clinical picture at presentation.
AB  - Extrinsic allergic alveolitis occurs rarely in childhood. We present 5 cases and
      briefly review the literature regarding this condition in the pediatric
      population. This report includes all cases (n = 5) of extrinsic allergic
      alveolitis known to have occurred in childhood on Malta. All cases were males,
      and were initially misdiagnosed as having other respiratory illnesses or mental
      disturbances. The diagnosis was based on a history of exposure to birds, clinical
      findings, positive avian precipitins, a restrictive defect on pulmonary function
      tests, and a suggestive chest X-ray appearance. All were treated with high-dose
      oral steroids for 3-4 weeks, with excellent response. Although these patients
      appear to have suffered no long-term sequelae, delayed diagnosis can lead to
      irreversible pulmonary fibrosis. The diagnosis of extrinsic allergic alveolitis
      should be entertained early in the differential diagnosis of children presenting
      with unusual respiratory symptoms and signs.

PMID- 10922138
TI  - Congenital tracheobiliary fistula.
AB  - Congenital respiratory tract-biliary fistula, including tracheo- and broncho
      biliary fistulae, are rare developmental anomalies. To date, only 18 cases have
      been reported. We present two additional cases that came to our attention after a
      long and difficult attempt to make a diagnosis. After surgical excision of the
      tract both children have remained symptom-free for 6 and 4 years, respectively.
      Bronchoscopy allows an early diagnosis, but patients also have to be investigated
      for associated biliary tree malformations.

PMID- 10922139
TI  - Selected abstracts

PMID- 10922140
TI  - Preface

PMID- 10922141
TI  - Issues and unmet needs in pediatric asthma.
AB  - Asthma is common and becoming more so in childhood. Although mild asthma may
      incur low average annual costs per child, these estimates need to be viewed in
      the context of the very large numbers of affected individuals. Whereas asthma and
      wheezing illness in childhood had in the past been broadly subdivided into asthma
      (often associated with atopy) and wheezy bronchitis (wheeze only, with associated
      upper respiratory tract infection), this distinction was lost during the 1970s in
      view of the demonstrated underdiagnosis and undertreatment of symptomatic school
      age children. The acceptance of asthma as a chronic inflammatory disease and
      evidence for airway remodeling and progressive deterioration in airway function
      in association with symptoms and atopy have led to earlier use of topical
      steroids at higher starting doses delivered by improved age-appropriate devices.
      Treating all children as if they were destined to become atopic asthmatics and at
      risk of airway remodeling may not be rational, particularly in those whose
      symptoms will subsequently resolve. However, there are as yet no screening tests
      which can clearly identify individuals at risk of long-term chronic airway
      inflammation and airway remodeling. The large number of infants and young
      children with current symptoms suggestive of asthma and in whom resolution is
      likely in the majority poses problems for the clinician in deciding the best
      initial therapy. There is an urgent need to develop simple and reliable measures
      that can identify the early manifestations of atopic airway sensitisation and to
      establish the place of early intervention with nonsteroidal drugs, including
      leukotriene antigonists.

PMID- 10922142
TI  - Role of leukotrienes in asthma pathophysiology.
AB  - Inflammation is an essential component of asthma pathophysiology. While beta(2)
      agonists are often used for short-term relief of acute bronchospasm, anti
      inflammatory agents are required for the long-term management of chronic
      inflammation in this disease. Corticosteroids have emerged as the first-line anti
      inflammatory therapy for asthma management. However, in some patients, especially
      children, the high doses of corticosteroids that may be required to control
      features of hyperresponsiveness, including exercise-induced asthma, raise safety
      concerns. Thus, there is a need for complementary anti-inflammatory, steroid
      sparing agents in asthma therapy. Several inflammatory mediators have been
      targeted in an attempt to thwart this inflammatory process, but so far with
      little success. The cysteinyl leukotrienes (CysLT), LTC(4), LTD(4), and LTE(4),
      have been shown to be essential mediators in asthma, making them obvious targets
      for therapy. These cysteinyl leukotrienes, previously known as the slow-reacting
      substance of anaphylaxis (SRS-A), mediate many of the features of asthma,
      including bronchial constriction, bronchial hyperreactivity, edema, and
      eosinophilia. Data show that selective cysteinyl leukotriene receptor antagonists
      (CysLTRAs) effectively reverse these pathologic changes. Corticosteroids do not
      inhibit the production of CysLTs in vivo, suggesting that CysLTRAs and
      corticosteroids affect different targets. The bronchodilator properties of
      CysLTRAs seem to be additive to those of beta(2)-agonists and corticosteroids.
      These data suggest that CysLTs are important therapeutic targets in the
      management of inflammation in asthma.

PMID- 10922143
TI  - Role of leukotriene receptor antagonists in pediatric asthma.
AB  - During the past decade, the inflammatory mechanisms that result in the clinical
      syndrome we call asthma have been emphasized in research, publications, and the
      various asthma management guidelines. This information clearly emphasizes the
      treatment of asthma with maintenance controller therapies early after the onset
      of symptoms in all but the very mildest of patients. Until the advent of the
      leukotriene receptor antagonists, nearly all of these maintenance therapies
      needed to be administered by inhalation through a variety of devices and spacers.
      Inhalation of medication was necessary to either increase the amount of drug
      reaching the airways or to increase the therapeutic index of drugs such as
      corticosteroids. Even under the best circumstances, this route of administration
      is difficult and expensive for many parents whose children have asthma. Now that
      oral controller therapies (leukotriene receptor antagonists) are available for
      children, their role in clinical practice needs to be examined. The latest asthma
      management guidelines classify asthma into four groups of severity, and base
      treatment recommendations on the intensity of symptoms, need for rescue
      medications, and pulmonary function as measured by peak expiratory flow and
      forced expiratory volume in 1 sec (FEV(1)). The categories of mild intermittent,
      mild persistent, moderate persistent, and severe asthma in children will be
      addressed in this presentation by reviewing the available data on the use of the
      leukotriene receptor antagonist montelukast in children. Mild intermittent asthma
      can be typified by exercise-induced asthma, a common pediatric condition. In this
      often troublesome condition, montelukast demonstrated effectiveness at the end of
      a once a day dose by blocking the effects of this naturally occurring challenge.
      Drug regulatory approval of a new drug also includes patients with more regular
      symptoms who are usually classified as having persistent or moderate asthma. In
      these montelukast pediatric studies, approximately 40% of patients were already
      taking inhaled corticosteroids. Patients had improvements in FEV(1), symptoms,
      and rescue medication use, clearly showing an effect with once a day dosing.
      Pediatric data in severe asthma patients are more limited, but in such patients a
      therapeutic trial of montelukast would seem preferable to using systemic
      corticosteroids or increasing inhaled steroids to a level where adverse effects
      have an increasing potential of occurring. Montelukast has been available in the
      United States since March 1998 and has received excellent acceptance by
      physicians, parents, and patients. The 5-mg chewable tablet administered once a
      day in the evening in children aged 6-14 years apparently fills a previously
      unmet need in the treatment of pediatric asthma.

PMID- 10922145
TI  - Palliative care and head and neck cancer.

PMID- 10922144
TI  - Leukotriene receptor antagonists: efficacy and safety in children with asthma.
AB  - To date, only one study of chronic use of a leukotriene receptor antagonist in
      children has been published. The efficacy and safety of montelukast in children 6
      14 years of age with asthma (n = 336) was studied during an 8-week, double-blind,
      placebo-controlled trial. There was significantly greater improvement in forced
      expired volume in 1 sec (FEV(1)) from baseline for the montelukast group (8. 23%)
      compared to the placebo group (3.58%). There was a significant decrease in use of
      beta agonists for symptom relief and a significant decrease in the percentage of
      days and percentage of patients with asthma exacerbations. An asthma-specific
      quality of life questionnaire revealed significant overall improvement in quality
      of life and significant improvement in the quality of life domains for symptoms,
      activity, and emotions. Adverse effects were not significantly different for
      montelukast than for placebo, with the exception of allergic rhinitis which was
      more prevalent in the placebo group. A 6-month open follow-up of patients from
      the above study was undertaken. Effects of montelukast on FEV(1) were consistent
      over the 6 months, with the increase in FEV(1) not significantly different from a
      small control group treated with beclomethasone. Quality of life remained
      significantly improved throughout the open treatment period. In conclusion,
      leukotriene receptor antagonists are of value for the treatment of children with
      asthma.

PMID- 10922147
TI  - Management of severe postnasal haemorrhage: the Kingsley splint revisited.
AB  - Postnasal haemorrhage accompanying severe craniofacial trauma may have
      catastrophic consequences if not arrested promptly. The airway has usually been
      secured and the cervical spine stabilized, but apart from fluid replacement,
      other attempts to control haemorrhage in the resuscitation room of the accident
      and emergency department may be to no avail. We wish to draw attention to a
      simple device that was introduced over 100 years ago and which may rapidly aid
      haemostasis and prevent the onset of hypovolaemic shock.

PMID- 10922146
TI  - A prospective, quantitative study on the clinical outcome of lingual nerve
      repair.
AB  - We previously showed in laboratory studies that the most effective method for
      repair of damaged lingual nerves was by excision of the neuroma, mobilization of
      the stumps, and direct reapposition with epineurial sutures. We have now
      undertaken a prospective study in a series of 53 patients treated by this method
      and have evaluated the outcome by quantifying and comparing the results of tests
      of sensation before and after operation. The outcome in individual patients was
      variable. However, pooled data from all patients showed a highly significant
      improvement in sensation at the final assessment 12 months or more after the
      repair. The proportion of patients who responded to most or all light touch
      stimuli increased from 0% to 51% after repair, and the proportion who responded
      to pin-prick stimuli increased from 34% to 77%. There was no correlation between
      the final results of any of the tests and the delay before repair. None of the
      patients regained completely normal sensation and there was no reduction in the
      number with spontaneous paraesthesia or pain. However, fewer patients tended to
      bite the tongue by accident and most of them considered the operation worthwhile.
      These data show that lingual nerve repair is effective in most patients and we
      suggest that it should be offered to all those who show few signs of spontaneous
      recovery after injury.

PMID- 10922148
TI  - Of humans and hamsters: comparative analysis of lipid peroxidation, glutathione,
      and glutathione-dependent enzymes during oral carcinogenesis.
AB  - We examined the extent of lipid peroxidation and the amount of reduced
      glutathione (GSH), and activities of the GSH-dependent enzymes, glutathione
      peroxidase (GPx) and glutathione S-transferase (GST), in human oral tumour tissue
      and 7, 12-dimethylbenz[a]anthracene-(DMBA)-induced hamster buccal pouch tumour
      tissues. Diminished lipid peroxidation in the oral and hamster tumours was
      accompanied by a significant reduction in the concentration of phospholipids and
      an increase in the cholesterol:phospholipid ratio. The concentration of
      glutathione and the activities of GPx and GST were raised in both human oral and
      hamster tumour tissues. Our results show that the patterns of changes in human
      oral squamous cell carcinomas and chemically-induced carcinomas of the hamster
      buccal pouch are similar.

PMID- 10922150
TI  - Sinusitis as the first indication of sarcoidosis an incidental finding in a
      patient with presumed 'odontogenic' sinusitis: case report.
AB  - Involvement of the paranasal sinuses and nose by sarcoidosis is uncommon, and has
      been reported in only 1-4% of patients with sarcoidosis. Clinical symptoms are
      nasal obstruction, epistaxis, nasal pain, discharge, anosmia or hyposmia,
      epiphora, and dyspnoea. We present a case of sarcoidosis in which sinusitis was
      the first clinical sign of the disease.

PMID- 10922149
TI  - Chemical cleaning of titanium tray for reconstructive surgery.
AB  - AIMS: To find out the extent of chemical contamination on the surface of titanium
      wrought mesh before and after swaging, and to assess the effectiveness of
      cleaning off these contaminants by various chemical methods. MATERIALS AND
      METHODS: Qualitative analysis of the surfaces of 6 wrought titanium meshes by
      scanning electron microscopy (EM) and radiological microanalyser. One of these
      meshes was subjected to experimental cleaning by different methods. Qualitative
      chemical analysis of 20 titanium trays fabricated for clinical use before and
      after acid cleansing. RESULTS: All 6 titanium meshes had surface contaminants,
      with silicon being the most common. The effective cleaning methods were chemical
      cleaning with Titaclean, mechanical trimming, or polishing with diamond paste.
      The 20 swaged titanium trays were effectively cleaned with either Titaclean or
      Chemi-Polish solution. CONCLUSION: Previously unknown surface contamination was
      common on wrought titanium mesh. Ultrasonic cleansing with Titaclean or Chemi
      Polish effectively removed most of the contaminants on the titanium trays before
      they were implanted.

PMID- 10922151
TI  - Failed closed reduction of a bifocal mandibular fracture because of dislocation
      of the mandibular ramus behind the styloid: case report.
AB  - We present an unusual dislocation of the mandibular ramus after a low condylar
      fracture associated with a fracture of the opposite body of mandible. As closed
      reduction failed, both fracture sites were exposed. The mandibular ramus was
      dislocated behind the styloid process, which was not shown on the preoperative
      radiographs. The intermediate fragment was freed and the fractures treated by
      miniplate osteosynthesis. The patient made an uneventful recovery with no
      residual deformity.

PMID- 10922152
TI  - Hearing loss associated with maxillectomy.
AB  - Little has been reported about the effect on auditory tube function of ablative
      surgery for maxillary neoplasms. Operations on the muscles of the soft palate may
      cause conductive hearing loss by impairing the opening of the auditory tube,
      which results in a middle ear effusion. Sensorineural hearing loss may also
      follow adjuvant radiotherapy. In this retrospective study we aimed to assess
      hearing status in patients who had undergone maxillary surgery for neoplastic
      disease between 1987 and 1997. Data recorded included personal details, site and
      size of lesion, treatment, and histology. Thirty-eight patients were identified,
      of whom 26 had survived and were contacted. Seventeen of the 26 had had part of
      the soft palate excised. All patients underwent tympanometry and had a pure tone
      audiogram. Audiograms showed an air-bone gap of > 10 dB in the ear on the side of
      the operation in 11 of those 17 patients. All 17 patients who had had soft palate
      resections had evidence of auditory tube insufficiency on tympanometry. Seven of
      the nine patients who had had radiotherapy had substantial sensorineural hearing
      loss. We conclude that conductive hearing loss is dependent on the site of
      resection; tympanometry is a sensitive test of middle ear function; sensorineural
      hearing loss may often follow radiotherapy; and audiological assessment is
      essential both before and after operation in patients having maxillary
      resections.

PMID- 10922153
TI  - Use of an 'osteocompressor' to avoid damage to the inferior alveolar nerve in the
      mandibular setback procedure: can the positive effects of osteodistraction be
      used in reverse? An experimental study in dogs.
AB  - We have designed an osteocompressor to try and avoid damage to the inferior
      alveolar nerve during sagittal split setback osteotomy of the mandibular ramus,
      and tested it on the mandibles of 10 dogs. The osteocompressor bears a
      superficial resemblance to an osteodistractor, but has a different internal
      structure that allows it to compress rather than distract. We were able to
      compress the neurovascular canal, the neurovascular bundle, the cancellous bone,
      and the mandible in dogs at a rate of 1 mm/day by rotating the screw of the
      compressor 1.5 times. We conclude that in dogs the neurovascular canal and
      neurovascular bundle can be compressed with this device without loss of
      sensation. We believe that this is the first publication on nerve canal
      compression and osteocompression.

PMID- 10922154
TI  - Doppler sonography for the assessment of central mandibular blood flow.
AB  - In this study we evaluated the role of Doppler sonography in the assessment of
      central mandibular blood flow. We assessed the characteristics of blood flow in
      the mental artery, the larger terminal branch of the inferior alveolar artery, in
      30 healthy volunteers equally distributed in the age groups 20-39, 40-59 and over
      60 years. We used a DWL Multi-Dop X4(R) Doppler sonography machine (DWL GmbH)
      with an 8 MHz probe applied intraorally. The variables analysed were patency,
      time averaged maximum velocity (TAMV), pulsatility index (PI), discomfort and the
      duration of the procedure. All the arteries analysed were patent. The TAMV and PI
      decreased as age increased and there were significant differences between the age
      groups: TAMV (P = 0.01), PI (P = 0.006). Pair-wise comparisons also showed
      significant differences (P< 0.05) between the 20-39 and the over 60 age group, 40
      59 and the over 60 age group for TAMV, and between the 20-39 and over 60 age
      group for PI. The difference in measurements between the right and left sides in
      individual patients was not significant. The assessment took about 20 minutes and
      caused little discomfort. The technique is simple and could potentially be used
      to influence clinical decisions.

PMID- 10922155
TI  - Sterilization of elastic ligatures for intraoperative mandibulomaxillary
      immobilization.
AB  - Sterilization can influence the mechanical properties of elastic ligatures used
      for mandibulomaxillary immobilization. The aim of this study was to compare
      different sterilization protocols (ethylene oxide, autoclave, irradiation, plasma
      sterilization, povidone-iodine for 24 hours and 70% isopropyl alcohol for 24
      hours) of three elastomers (natural rubber, silicone rubber, and polyurethane).
      Three mechanical variables were assessed in a testing machine: breaking strength,
      tensile strength and tensile strength after a 24-hour load (material fatigue).
      Natural rubber was most susceptible to mechanical alteration by sterilization and
      lost 46% of its breaking strength and 43% of its tensile strength after
      autoclaving. Polyurethane was more resistant (multiple comparison, Tukey-Kramer),
      but polyurethane ligatures stuck together after autoclaving. The protocols for
      low-temperature sterilization, ethylene oxide, irradiation, and plasma were
      superior to autoclaving and the disinfecting solutions. These data suggest that
      polyurethane sterilized with ethylene oxide is the material of choice.

PMID- 10922156
TI  - Evaluation of skeletal stability following surgical correction of mandibular
      prognathism.
AB  - This retrospective study was designed to assess skeletal stability after the
      correction of mandibular prognathism by sagittal split osteotomy (SSO) and
      intraoral vertical subsigmoid osteotomy (VSO). We used lateral cephalographs of
      31 patients taken before, immediately after, and at least one year after the
      operation. We recorded euclidean distance matrix analysis, linear and angular
      measurements, and x and y co-ordinates of cephalometric landmarks for each
      cephalograph. There were no significant differences in extent of the mandibular
      retrognathia or magnitude of change between the two groups. The main significant
      changes in both groups were reduction of the total mandibular length, and
      posterior shifting in the mandible. One year after the operation the main change
      was the mean forward relapse of 2.5 mm in the SSO group and the mean posterior
      relapse of 0.5 mm in the VSO group. The difference in skeletal stability between
      the groups was significant (P< 0.05), and we conclude that VSO is the more
      effective technique for correcting mandibular prognathism.

PMID- 10922158
TI  - The epidemiology of lip, oral cavity and pharyngeal cancers in Kuwait 1979-1988.
AB  - Of the 10 539 cases of cancer recorded in the Kuwait Cancer Registry in the 10
      years 1979-1988, 784 (7.4%) involved the lip, oral cavity or pharynx. Nearly half
      of these were of the nasopharynx or salivary glands, and the incidence of
      salivary gland cancer appears to be increasing. The aetiology may be related to
      poor oral hygiene and tobacco-smoking.

PMID- 10922157
TI  - Guided bone regeneration with titanium membranes: a clinical study.
AB  - Guided bone regeneration using barrier membranes is useful in bone augmentation.
      Because the commonly used polytetrafluoroethylene (PTFE, Gore-Tex (R), WL Gore,
      Flagstaff, AZ, USA) membranes or resorbable membranes tend to collapse, more
      stable membranes are desirable. A titanium membrane (FRIOS(R) BoneShield,
      Friatec, Mannheim, Germany) was evaluated in a clinical study of 52 patients.
      Most of them had particulate bone grafts or phycogene hydroxyapatite
      (Algipore(R), Friatec, Mannheim, Germany) or both stabilized with titanium
      membranes. In 78 procedures, 23 membranes (29%) became exposed, but only seven of
      these (9%) led to failure of the graft with a considerable loss of augmented
      material. The time interval between operation and possibly exposure was
      responsible for the result. Early exposures (within a few weeks) led to poor
      formation of new bone within the grafts, whereas if exposure was later, results
      were as good as in procedures in which the membranes did not become exposed.

PMID- 10922160
TI  - Free tissue flaps: a new way to position the pedicle.
AB  - A simple and atraumatic method for passing the pedicle from a free flap through a
      subcutaneous tunnel using a modified Yankauer sucker tube is described.

PMID- 10922159
TI  - Patterns and appropriateness of referral from general dental practice to
      specialist oral and maxillofacial surgical services.
AB  - In this study we investigated patterns of referral and appropriateness of
      referrals to specialist oral and maxillofacial surgery services, using postal
      questionnaires and referral letters. The most common reasons for referral were
      the expected difficulty of the operation, the medical condition of the patient
      and the lack of facilities for general anaesthesia. Most referrals were made to
      the oral and maxillofacial surgery department of a general hospital but almost
      three-quarters of the respondents stated that they would refer patients to
      specialist surgical dentistry practices in the future. Few referrals to a
      university department of oral and maxillofacial surgery were considered to be
      inappropriate, nor were requests for a particular type of anaesthesia. Any future
      transfer from secondary to primary care for oral surgery may be hindered by the
      reduction in facilities for general anaesthesia in the primary care setting.

PMID- 10922162
TI  - Use of theatre time for dentoalveolar operations under general anaesthesia.
AB  - Efficient use of hospital resources is essential if waiting lists are to be
      reduced. We undertook this study because there seems to be little information on
      the use of theatre time for dentoalveolar surgery under general anaesthesia. The
      time taken for each sequence of events (from start of case, induction, operation
      to recovery, and so on) for each patient was recorded. Of the 30 lists examined,
      22 lists (73%) finished on time or early, and 8 lists (27%) ran late. The time
      spent operating occupied less than 50% of theatre time available. The 'total
      time' for each case was increased (by about 10 minutes a patient) when a junior
      anaesthetist was anaesthetizing rather than a consultant. The overall time used
      per list was 79% with the remaining 21% of the list being 'unused'. Where these
      lists did over-run, then this was usually because the operation took longer,
      although grade of anaesthetist was a factor. We identified several areas in which
      efficiency could be improved.

PMID- 10922161
TI  - Rate of loss of irradiated polyglactin 910 (Vicryl Rapide) from the mouth: a
      prospective study.
AB  - We aimed to find out how long irradiated polyglactin 910 (Vicryl Rapide) remained
      in the oral tissues and to investigate the effect of chlorhexidine mouthwash on
      absorption time and bacterial growth on sutures. Twenty-one volunteers each had
      two Vicryl Rapide sutures placed intraorally under local anaesthesia. Ten of
      these subjects used chlorhexidine mouthwash twice daily. After 7 days, one suture
      was removed to be cultured for aerobic and anaerobic bacteria. The other was
      monitored for time from insertion to loss. The median survival value was 3 days
      (range 1-13). The median number of days to suture loss was less in the
      chlorhexidine group (3, range 1-11) than in the control group (4, range 1-13) but
      this was not significant. There were no significant differences in aerobic and
      anaerobic counts between the two groups. Vicryl Rapide may be useful for
      intraoral use.

PMID- 10922163
TI  - Use of a resorbable fixation system in orthognathic surgery.
AB  - We present our early experience with the use of a resorbable plating system in
      orthognathic surgery. Thirty-one patients who have finished growing and who had
      dentofacial deformities that were not part of syndromes were treated by routine
      orthognathic repositioning procedures: maxillary (n = 8) and mandibular (n = 9)
      osteotomies, or bimaxillary procedures (n = 14). All skeletal fragments were
      fixed with resorbable plates and screws. The follow-up period ranged from 2-8
      months (mean 5). All the patients recovered normally except for one who developed
      a localized buccal space infection. In the early postoperative period, six
      patients had mild mobility of the maxilla, but stability was within normal limits
      at six weeks postoperatively. We conclude that, though technique has an important
      influence on success, LactoSorb is a good fixative for maxillo-mandibular
      repositioning.

PMID- 10922164
TI  - Expression of nitric oxide synthase in pleomorphic adenomas of the parotid.
AB  - The actions of nitric oxide (NO) in the pathology of solid tumours are
      complicated and many are poorly understood because NO has both inhibitory and
      tumour-promoting activities. In the current study we aimed to find out
      immunohistochemically whether the expression of both the inducible (iNOS) and
      endothelial (eNOS) forms of the enzyme nitric oxide synthase (NOS) were changed
      in pleomorphic adenomas of the parotid compared with normal salivary tissue.
      There was a significant difference in staining for iNOS between the tumour and
      normal salivary tissue, with tumour epithelial cells being stained in 29 cases of
      the 30 cases studied (P< 0.0001). The luminal cells of the salivary ducts also
      stained, but not the normal salivary tissue. Immunohistochemistry for the eNOS
      isoenzyme showed moderate staining of the tumour epithelium in only three
      specimens. There was also mild staining in the salivary duct cells of the normal
      glandular tissue and in endothelium of blood vessels in both tumour and normal
      glandular tissue in the same 29 cases.

PMID- 10922165
TI  - Clinical experience with the negative pressure wound dressing.
AB  - Between 1997 and 1999, more than 300 patients have been treated using negative
      pressure wound dressings. The technique has been used successfully to prepare
      various acute, chronic or infected wounds to accept a skin graft or flap, and to
      promote graft take at difficult donor sites. The advantages include rapid healing
      by secondary intention, reduced time to skin grafting, an increase in the rate of
      graft take and a reduction in donor site complications. The dressing can be
      applied quickly and easily and there have been no serious complications.

PMID- 10922166
TI  - Discoplasty with autogenous superficial musculoaponeurotic system (SMAS) flap in
      reconstruction of the temporomandibular joint combined with cervicofacial
      rhytidectomy.

PMID- 10922167
TI  - Influence of orthodontic treatment on development of third molars.
AB  - We aimed to find out whether extraction of lower premolars and subsequent closure
      of the space by a fixed appliance influenced the chances of mandibular third
      molars erupting. We compared angular and linear measurements of lower third
      molars on dental panoramic tomograms in 30 orthodontic patients with similar
      measurements from 30 patients with impacted third molars in intact arches. We
      found that the mesial angulation of lower third molars was reduced from 50
      degrees to 43 degrees by orthodontic treatment (P< 0.001). Distance to the
      occlusal plane was reduced from 12 mm to 10 mm (P< 0.001). The space available
      increased from 4 mm to 11 mm (P< 0.001). We conclude that extraction of lower
      premolars and orthodontic treatment to achieve complete closure of the space
      allowed the positions of many impacted lower third molars to improve
      significantly.

PMID- 10922168
TI  - Matrix metalloproteinase and tissue inhibitor of metalloproteinase in serum and
      lavage synovial fluid of patients with temporomandibular joint disorders.
AB  - We measured matrix metalloproteinases (MMPs) and tissue inhibitor of
      metalloproteinases (TIMP) in temporomandibular joint (TMJ) disorders. All
      patients were fully investigated, by visual analogue pain scores, plain
      radiographs and double-contrast arthrotomograms. The patients were grouped
      according to whether or not they were in pain. There were 35 patients with
      painful joints; 16 painless crepitating joints and 10 with chronic closed locked
      joints. A further group of 9 volunteers with no symptoms of TMJ abnormalities
      were used as controls. We found that synovial fluid concentration of MMP-3 was
      significantly increased (1117.2 (164.0) ng/ml) (P< 0.05) in the painful group
      compared with controls (436.2 (94.8) ng/ml) and with the two groups with painless
      TMJ (475.0 (113. 0) ng/ml/crepitation, and 516.0 (115.1) ng/ml/closed locked
      joints). MMP-1 and TIMP-1 were not recordable in most joints, and the serum
      concentrations of MMP-1, MMP-3, and TIMP-1 were similar to those in controls in
      all groups. There was no correlationship between MMP-3 concentration and joint
      morphology as shown by plain radiographs and double contrast arthrotomograms.
      These findings indicate that the synovia of painful joints are inflamed.

PMID- 10922170
TI  - Oral lichen planus: a review.
AB  - Oral lichen planus is a disease that can persist in some patients for a long
      time. The buccal mucosa, tongue and gingiva are the most common sites, whereas
      palatal lesions are uncommon. Oral lichen planus affects women more often than
      men in a ratio of 2:3. It can present in a number of forms: reticular, papular,
      plaque-like, erosive, atrophic and bullous. The question of malignant
      transformation of oral lichen planus remains controversial. The management can be
      non-surgical or surgical and the choice of treatment may vary from patient to
      patient and depends on the choice of the clinician.

PMID- 10922169
TI  - Total prosthetic replacement of the TMJ: experience with two systems 1988-1997.
AB  - We report our experience with the Vitek VK II and the Christensen systems for
      total prosthetic replacement of the temporomandibular joint, in 62 patients
      treated between 1988 and 1997. Thirteen were treated in Birmingham and 49 in
      Gloucester. A total of 86 joints were replaced, of which 27 (31%) were Vitek VK
      II and 59 (69%) were Christensen prostheses. Just over half of the patients were
      treated for degenerative arthropathy or osteoarthritis, and the second most
      common diagnosis was rheumatoid arthritis. Twenty-five patients had had previous
      operations. The median follow-up was 14.5 months (range 1-120). Preoperatively
      only 14 patients (23%) could eat all types of food - and postoperatively this
      increased to 48 (77%). Thirty-nine patients (63%) reported severe pain
      preoperatively compared with three (5%) postoperatively. No prostheses were
      rejected, but four patients required replacement of Vitek VK II by Christensen
      prostheses; all four showed histological evidence of a foreign body giant cell
      reaction. The overall success rate was 58/62 patients and 81/86 joints replaced
      (94% in each case). However, for the Vitek VK II system alone the success rate
      was 14/17 patients (82%) and 24/27 joints replaced (89%).

PMID- 10922172
TI  - Trismus: a bizarre finding.

PMID- 10922171
TI  - Mandibular fracture after wire suspension reduction technique in patient with
      HIV.

PMID- 10922173
TI  - Osteogenesis imperfecta.

PMID- 10922175
TI  - Fatigue fracture of stainless steel plate.

PMID- 10922174
TI  - Unusual histological type of oral papilloma, mimicking sinonasal tract papilloma
      (transitional cell papilloma)

PMID- 10922176
TI  - Disease-specific survival for a new t-stage of oropharyngeal cancer.

PMID- 10922177
TI  - Re: Vander Lei et al. Closure of radial forearm free flap donor site with local
      full-thickness skin graft.

PMID- 10922178
TI  - Dentigerous cyst versus dental follicle.

PMID- 10922179
TI  - Clearance of level IV in squamous carcinoma of the tongue.

PMID- 10922180
TI  - Foreign body in the floor of the orbit.

PMID- 10922181
TI  - Re: Nunez et al. Prophylactic plating of the donor site of osteocutaneous radial
      forearm flap. Br J Oral Maxillofac Surg 1999; 37: 210-212.

PMID- 10922183
TI  - Notices

PMID- 10922182
TI  - Re: Hardee et al. Planning the consultant workforce in oral & maxillofacial
      surgery.

PMID- 10922184
TI  - Reports and declarations are useful, but not self-executive.

PMID- 10922185
TI  - Munich Declaration--nurses and midwives: a force for health.
AB  - The Second WHO Ministerial Conference on Nursing and Midwifery in Europe
      addresses the unique roles and contributions of Europe's six million nurses and
      midwives in health development and health service delivery. Since the first WHO
      ministerial conference that took place in Vienna over ten years ago, some steps
      have been taken in Europe towards strengthening the status and making full use of
      the potential of nurses and midwives.

PMID- 10922186
TI  - Expert critical care nurses' use of pulmonary artery pressure monitoring.
AB  - Critical care nurses make numerous complex decisions during their day-to-day
      practice. General themes in previous decision-making studies have included the
      influence of knowledge and previous experience, the increasing complexity of
      decisions made and the change in decision-making processes used as the nurse
      progresses from a novice to an expert practitioner. This paper reports one
      component of a study which used a concept attainment framework to determine what
      data were used by eight expert critical care nurses in relation to haemodynamic
      monitoring. Results indicated that pulmonary artery pressure monitoring was used
      to attain the concepts of preload, cardiac output and blood pressure. In
      addition, participants used few clinical assessment attributes, but collected a
      large number of attributes which they arranged around three to five central
      concepts and took a broad view of haemodynamic assessment. One participant did
      not display many of the decision-making features normally associated with an
      expert practitioner. In conclusion, expert critical care nurses process an
      immense amount of data in a short space of time. However, they may not use all
      available data. Evidence suggests not all nurses who practise in the field for a
      lengthy period reach the level of an expert.

PMID- 10922187
TI  - Issues surrounding educational preparation for intensive care nursing in the 21st
      century.
AB  - Major changes in intensive care provision, nursing and nurse education over the
      last ten years mean that it is a crucial time to take a look at the effectiveness
      of the post-registration intensive care nursing course [ENB 100]. This article
      examines whether nurse education is able to meet the current and future
      challenges. A call for more research regarding the effects of nurse education
      courses on participants' clinical practice is advocated. Key factors examined
      include teaching and learning strategies, the identification of common threshold
      core and specific competencies, and the assessment of practice. Post-registration
      assessment of practice within the writers' own educational institution is
      evaluated. Valid and reliable assessment which differentiates between the level
      of skills attainment of students and identifies the stage of development of the
      nurse (Benner 1984) is recommended. The question of who benefits from the current
      provision of ENB 100 courses is considered. It is argued that clinical and
      educational staff should work together to ensure nurses who undertake ENB 100
      courses emerge 'fit for purpose' (DoH 1997a).

PMID- 10922188
TI  - A review of intensive care nurse staffing practices overseas: what lessons for
      Australia?
AB  - In view of market-driven health-care policies and the move to greater
      efficiencies within the health-care system, the cost of nursing care is being
      increasingly scrutinised. Different overseas practices are commonly cited as
      justification for changing practices within Australia. This study is based on a
      review of the literature on intensive care nurse staffing requirements in
      Australasia; specifically, New South Wales, the United States (US) and, to a
      lesser extent, Europe. It was found that looking to the US for cost-cutting
      strategies in intensive care units (ICUs) is based on a false premise: that we
      are comparing like with like. ICUs in the US have a different historical
      trajectory and culture, service wider constituencies, have technicians and
      unregistered personnel providing nursing care and do not provide demonstrably
      better outcomes or significant cost savings. Research indicates that continuous
      nursing care by trained professionals provides the best outcomes. If costs must
      be cut, technology, pharmaceuticals and laboratory tests should be targeted.
      Further, a greater commitment to the development of a 'progressive patient care'
      model in hospital planning is required, in order to establish or consolidate an
      intermediate level of nursing care between the ward and the ICU. Programs aiming
      to improve and continuously monitor patient care, such as adverse event
      monitoring, the prevention of unplanned extubation and facilitation of early
      extubation, should be instituted, as these have been shown to not only reduce ICU
      costs but also improve patient outcomes. (c) 2000 Harcourt Publishers Ltd.

PMID- 10922189
TI  - Team nursing and ITU--a good combination?
AB  - Deficits in 'measurable care', in an 11-bedded intensive care unit, prompted a
      pilot study of team nursing. Team nursing was introduced for three beds out of
      the total 11 for a period of six months. In order to evaluate the effects,
      aspects of care and job satisfaction were measured and compared between the team
      nursing beds and the rest of the unit. The study revealed that job satisfaction
      and the levels of 'measurable care' did not improve whilst team nursing was
      practised. Based on this evidence, the authors question the relevance of team
      nursing in this particular intensive therapy unit (ITU) and maintain that the
      best method of delivering nursing care in ITU remains unclear.

PMID- 10922190
TI  - Acute myocardial infarction in middle-aged women: narrations from the patients
      and their partners during rehabilitation.
AB  - The purpose of this study was to examine the meaning of lived experiences after
      an acute myocardial infarction (AMI) and being a partner to an afflicted woman,
      as it is narrated during rehabilitation. Nine women and their partners narrated
      their experiences three and twelve months after AMI. The interview texts were
      transcribed and then interpreted, using a phenomenological-hermeneutic method
      inspired by the philosophy of Ricoeur. The result showed that their experiences
      of the illness contained two themes: 'rehabilitation needed' and 'loss of
      freedom' which contains eight sub-themes; 'adapting to it', 'struggling against
      it', 'living as normally as possible', 'having insight into how it can be',
      'feeling guilty and ashamed about being weak', 'withholding feelings', 'feeling
      useless', and 'feeling fatigued and losing strength'. After further
      interpretation, the themes gave a deeper meaning of living with AMI and how it
      affects women and their partners. The women conceded that they felt distressed
      and vulnerable but struggled against the fear the illness means. The partner's
      role appears to be one of trying to adapt to the women's experiences of the
      illness. That the women withheld their feelings and did not talk about them
      indicates a lack of communication between the couples. As coronary care nurses
      often come very close both to the afflicted persons and the relatives they fill
      an important function in each patient's recovery. The nurses could help and
      prepare the patients and their relatives to understand better such feelings and
      reactions as could appear after discharge from hospital.

PMID- 10922193
TI  - Chest X-ray quiz.

PMID- 10922191
TI  - Bupropion (Zyban) for smoking cessation.

PMID- 10922194
TI  - Oral acyclovir for herpes simplex virus eye disease: effect on prevention of
      epithelial keratitis and stromal keratitis. Herpetic Eye Disease Study Group.
AB  - OBJECTIVES: To investigate the effect of oral acyclovir therapy for recurrences
      of herpes simplex virus (HSV) epithelial keratitis and stromal keratitis and to
      determine if certain patients derive differential benefit. DESIGN: This
      randomized, double-masked clinical trial enrolled 703 immunocompetent patients
      with prior HSV eye disease within the preceding year; assigned 357 patients to
      receive oral acyclovir, 800 mg/d, and 346 to receive placebo; and followed up
      patients during a 12-month treatment period for the development of HSV eye
      disease. RESULTS: The cumulative probability of a recurrence of any type of
      ocular HSV disease during the 1-year treatment period was 19% in the acyclovir
      group compared with 32% in the placebo group. Sixteen patients in the acyclovir
      group and 30 in the placebo group had more than 1 recurrence. A benefit was seen
      for preventing both epithelial keratitis (rate ratio, 0.62; 95% confidence
      interval, 0.39-0.97) and stromal keratitis (rate ratio, 0. 57; 95% confidence
      interval, 0.36-0.89). Although a relative benefit of treatment on preventing any
      type of recurrence was present in most subgroups, the magnitude of absolute
      benefit was greatest among patients with the highest number of prior episodes of
      ocular HSV disease. The benefit in preventing stromal keratitis was seen solely
      among patients with a history of stromal keratitis. CONCLUSIONS: Long-term
      suppressive oral acyclovir therapy reduces the rate of recurrent HSV epithelial
      keratitis and stromal keratitis. Acyclovir's benefit is greatest for patients who
      have experienced prior HSV stromal keratitis. Arch Ophthalmol. 2000;118:1030-1036

PMID- 10922195
TI  - A comparative study of topical vs retrobulbar anesthesia in complicated cataract
      surgery.
AB  - OBJECTIVES: To evaluate and compare levels of patient discomfort and
      perioperative complications during phacoemulsification and implantation of a
      foldable intraocular lens under topical lidocaine hydrochloride and retrobulbar
      anesthesia in patients with cataract who also had exfoliation syndrome, uveitis,
      posterior synechia, phacodonesis, or previous intraocular surgery. DESIGN: A
      prospective, randomized, controlled trial was carried out at 2 institutions.
      PARTICIPANTS: A total of 476 eyes of 476 patients with various well-established
      risk factors fulfilled the inclusion criteria. In 238 eyes, phacoemulsification
      was performed under retrobulbar anesthesia, while the other 238 eyes received
      topical anesthesia. INTERVENTIONS: All patients underwent temporal clear corneal
      phacoemulsification and implantation of a foldable intraocular lens. Patients
      under retrobulbar anesthesia received a single injection (3. 5-5.5 mL) of a
      combination of 0.75% bupivacaine hydrochloride, 2% lidocaine, and hyaluronidase
      into the retrobulbar space. Patients in the topical anesthesia group received a
      minimum of 5 doses (approximately 40 microL per dose) of 2% topical lidocaine. No
      intracameral injection of any anesthetic was given. MAIN OUTCOME MEASURES: The
      number of complications and adverse events. The intraoperative conditions were
      judged by the surgeon (P.C.J. or F.K. J.), and a 10-point visual analog scale was
      used immediately after surgery to assess each patient's overall severity of
      intraoperative pain. RESULTS: The overall intraoperative complication rate was
      1.9% for capsular tear, 3.8% for zonular tear, 1.5% for vitreous loss, and 1.0%
      for iris prolapse. Apart from the incidence of vitreous loss, which was
      significantly (P =.041) lower in the topical anesthesia group, no statistically
      significant differences in intraoperative and early postoperative complications
      were found between the groups. A supplemental posterior sub-Tenon space injection
      was required in 1.3% of the topical anesthesia group and in 0.8% of the
      retrobulbar anesthesia group. Chemosis (2.5%), subconjunctival hemorrhage (1.7%),
      and periorbital hematoma (0.8%) were seen only in the retrobulbar anesthesia
      group. The mean + SE pain scores estimated by the patients were 0.84 + 1.30 in
      the topical anesthesia group and 0.73 + 1.50 in the retrobulbar anesthesia group
      (P =.41). Patient preference for topical anesthesia (91%) appeared to be
      significantly (P =.01) higher than for retrobulbar anesthesia (62%). The surgeons
      found anesthesia-related intraoperative difficulty to be slightly lower in the
      retrobulbar anesthesia group (8%) than in the topical anesthesia group (14%).
      CONCLUSIONS: Surgery-related complications and patient discomfort were similar
      for the 2 methods of anesthesia. Topical anesthesia is justified as a means of
      improving safety without causing discomfort to the patient even in complicated
      cases of cataract surgery. Arch Ophthalmol. 2000;118:1037-1043

PMID- 10922196
TI  - Assessment of retinal nerve fiber layer internal reflectivity in eyes with and
      without glaucoma using optical coherence tomography.
AB  - OBJECTIVE: To assess the internal reflectivity of the retinal nerve fiber layer
      in normal, ocular hypertensive, and glaucomatous eyes using optical coherence
      tomography. METHODS: All patients underwent complete ophthalmic examination and
      achromatic automated perimetry. Intraocular pressure was 21 mm Hg or less for low
      tension glaucoma and normal eyes and at least 25 mm Hg on 2 separate occasions in
      ocular hypertensive and high-tension glaucoma eyes. All glaucomatous eyes had
      characteristic glaucomatous optic neuropathy and associated achromatic automated
      perimetry defect. Relative retinal nerve fiber layer internal reflectivity was
      measured on optical coherence tomography images using a software program of our
      own design. RESULTS: We enrolled 98 eyes (19 normal, 34 ocular hypertensive, 17
      high-tension glaucoma, and 28 low-tension glaucoma). Relative internal
      reflectivity was less in eyes with glaucoma than in normal (P<.001, t test) and
      ocular hypertensive eyes (P<.001, t test). There was no difference in relative
      internal reflectivity between normal and ocular hypertensive eyes (P =.32) and
      between eyes with high-tension glaucoma and low-tension glaucoma (P =.43).
      Internal reflectivity correlated with mean deviation on achromated automatic
      perimetry (r(2) = 0.49, P<.001, quadratic regression analysis). CONCLUSION:
      Relative retinal nerve fiber layer internal reflectivity may provide useful
      information about the extent of retinal nerve fiber layer injury in glaucoma.
      Arch Ophthalmol. 2000;118:1044-1047

PMID- 10922197
TI  - Flicker sensitivity and cardiovascular function in healthy middle-aged people.
AB  - OBJECTIVE: To establish normative relations between measures of visual function
      and cardiovascular variables that are important for age-related disease,
      including various forms of glaucoma. METHODS: Foveal flicker sensitivities,
      resting blood pressures and heart rates, and intraocular pressures were measured
      in 18 individuals aged 40 to 68 years. All subjects had 20/20 or better visual
      acuity in the test eye and no evidence of eye disease or glaucoma suspicion on
      clinical evaluation and medical history. No subjects were using medication to
      lower blood pressure. Flicker sensitivity was measured by increasing the
      illuminance of a fully modulated 20-Hz test stimulus until flicker was perceived.
      Two test-background stimulus combinations were used: a 570-nm ("yellow") test on
      a predominantly long-wavelength ("magenta") background and a 580-nm ("yellow")
      test on a 580-nm ("yellow") background. The illuminance of the yellow background
      was dimmer than that typically used for short-wavelength automated perimetry,
      whereas the illuminance of the magenta background was greater. RESULTS: The 2
      flicker sensitivity measures were distinguished by the strong dependence of the
      magenta background measure on the ratio of mean arterial blood pressure to heart
      rate. Log flicker sensitivity on this background generally could be modeled as a
      linear combination of age, intraocular pressure, and ratio of mean arterial blood
      pressure to heart rate. The optimal model accounted for 84% of the variance (R =
      0.92) from all but 2 outlying individuals. After age and intraocular pressure
      effects were partialed out, an increasing ratio of mean arterial blood pressure
      to heart rate was strongly associated with decreasing flicker sensitivity.
      CONCLUSIONS: Reduced cardiovascular function impacts the ability of the normal
      visual system to adapt and regulate flicker sensitivity. Elevated intraocular
      pressure and increased age reduce flicker sensitivity relatively uniformly across
      a range of stimulus conditions. Because the ratio of mean arterial blood pressure
      to heart rate equals total peripheral vascular resistance multiplied by cardiac
      stroke volume, and because total peripheral resistance is determined largely at
      the arterioles, it is likely that even modest changes in arteriolar function are
      associated with measurable alterations of visual function. Arch Ophthalmol.
      2000;118:1049-1055

PMID- 10922198
TI  - Watzke-Allen slit beam test in macular holes confirmed by optical coherence
      tomography.
AB  - OBJECTIVE: To examine the role, validity, and interpretation of Watzke-Allen slit
      beam testing in patients with idiopathic senile macular holes. METHODS: Thirty
      seven consecutive patients with 40 full-thickness macular holes, confirmed on
      optical coherence tomography, were prospectively recruited. The Watzke-Allen slit
      beam test was used centrally and on the rim of the macular hole in both vertical
      and horizontal orientations. RESULTS: In 24 eyes, the beam was reported as
      thinned in both vertical and horizontal orientations when placed directly over
      the center of the macular hole. In 9 eyes, the Watzke-Allen slit was reported as
      broken in both vertical and horizontal orientations. In 6 eyes, the beam was
      reported as broken in one orientation and thinned in the other. In 1 eye, the
      beam was reported as kinked but not thinned or broken. When the beam was placed
      on the edge of the macular hole, all patients reported a displacement or bowing
      of the beam away from the center of the hole. CONCLUSIONS: These findings confirm
      tangential traction of photoreceptors from a central foveal dehiscence as the
      causative mechanism in the development of the majority of macular holes. Careful
      interpretation of the Watzke-Allen sign may offer a technique for preoperatively
      determining visual prognosis. Arch Ophthalmol. 2000;118:1059-1063

PMID- 10922199
TI  - Metastatic melanoma death rates by anatomic site after proton beam irradiation
      for uveal melanoma.
AB  - BACKGROUND: Ciliary body location is an established prognostic factor for
      metastasis-related death from uveal melanoma. We evaluated alternative approaches
      for classifying this covariate when constructing predictive models of patient
      survival. METHODS AND DESIGN: The analyses were based on a consecutive series of
      1848 primary choroidal and/or ciliary body melanoma patients treated with proton
      beam irradiation (70 cobalt gray equivalent in 5 fractions) at the Harvard
      Cyclotron Laboratory, Boston, Mass, between July 1975 and December 1995. For each
      patient, the anatomic site of the tumor was classified according to an estimate
      of the proportion of the tumor base lying anterior to the ora serrata. Using
      proportional hazards regression, we estimated relative risk ratios and death
      rates from melanoma metastasis according to the extent of ciliary body
      involvement. All estimates were adjusted for other established prognostic
      factors. RESULTS: Patients were followed up through April 30, 1998; none were
      lost to follow-up. Of 1848 patients analyzed, 378 died of melanoma metastasis.
      The median follow-up period among survivors was 9.5 years. Ciliary body origin
      (>50% of tumor base anterior to the ora serrata) was positively associated with
      tumor pigmentation (P<.001), tumor height (P<.001), and extrascleral extension of
      the tumor (P<.001). Compared with tumors involving only the choroid, melanoma
      associated death rates increased with the proportion of the tumor base lying
      within the ciliary body (P =. 006); the multivariate-adjusted relative risk ratio
      for greater than 75% involvement was 2.30 (95% confidence interval [CI], 1.26
      4.23). The covariate-adjusted 5-year death rates for ciliary body origin and
      choroidal origin were 15.9% (95% CI, 11.3%-21.2%) and 9.8% (95% CI, 8.3%-11.7%),
      respectively. CONCLUSION: Patients with melanomas of presumed ciliary body origin
      seem to be subject to a higher risk of death resulting from melanoma metastasis.
      Arch Ophthalmol. 2000;118:1066-1070

PMID- 10922200
TI  - The +10 diopter lens occluder.
AB  - BACKGROUND: It would be useful to be able to visualize the eye under cover during
      the cover test. Used as an occluder, a +10 diopter (D) lens will permit such
      visualization. It is important to know if a +10D lens creates dissociation that
      is qualitatively similar to an opaque occluder. METHODS: The angle of strabismus
      was measured in 33 patients with esotropia. Seventeen had intermittent exotropia,
      and 15 had dissociated vertical divergence with both an opaque occluder and a
      +10D lens used as an occluder. The findings were then compared. RESULTS: In 64 of
      the 65 patients participating in this study, the measurements obtained with the 2
      occluders agreed within 3 prism diopters on repeated testing. In the remaining
      patient, the measurements differed by 5 prism diopters. In all patients, the
      dissociated eye could be clearly visualized through the +10D lens. CONCLUSION: A
      +10D lens permits excellent visualization of the dissociated eye and provides
      measurements that are qualitatively similar to those obtained with a standard
      occluder. Arch Ophthalmol. 2000;118:1071-1073

PMID- 10922201
TI  - Aging affects the retrobulbar circulation differently in women and men.
AB  - BACKGROUND: While aging clearly has protean biological effects on every organ
      system, the differential effects of aging in women and men in the retrobulbar
      vasculature, to our knowledge, have never been investigated. Because glaucoma and
      age-related macular degeneration are closely linked to advanced age, we performed
      a cross-sectional study using color Doppler imaging of 4 retrobulbar vessels in
      both healthy women and men. OBJECTIVE: To define the influence of aging per se on
      ocular hemodynamics. METHODS: Women (n = 73) and men (n = 55), aged from 20 to 90
      years, free of ocular and systemic disease, and with normal intraocular pressure,
      were recruited for this study. Postmenopausal women who were not receiving
      estrogen replacement therapy were also recruited. Studies involved color Doppler
      imaging analysis of the ophthalmic, central retinal, and nasal and temporal
      posterior ciliary arteries. Ophthalmic arterial peak systolic and end-diastolic
      velocities and a Pourcelot resistance index were determined for each vessel.
      RESULTS: In both sexes, ophthalmic arterial end-diastolic velocity decreased and
      the Pourcelot resistance index rose with advancing age (each P<. 001); peak
      systolic velocity in the ophthalmic vessel was age-independent. In contrast,
      central retinal arterial flow velocities were unaffected by age in both sexes. In
      the posterior ciliary arteries, in men, flow velocities and the Pourcelot
      resistance index were independent of age. However, in women, end-diastolic
      velocity decreased with age in both the nasal and temporal posterior ciliary
      vessel (each P<.05); peak systolic velocity was constant; the Pourcelot
      resistance index in each ciliary artery rose with advancing age (each P<.05).
      CONCLUSION: In healthy women and men, aging-induced changes in retrobulbar
      hemodynamics are comparable to alterations seen in patients with glaucoma or age
      related macular degeneration, suggesting that vascular changes with senescence
      may contribute to increased risk for these diseases in older age. Arch
      Ophthalmol. 2000;118:1076-1080

PMID- 10922202
TI  - Comparison of different biomaterials for glaucoma drainage devices: part 2.
AB  - BACKGROUND: Inflammation associated with biomaterials may contribute to the
      failure of glaucoma drainage devices. OBJECTIVE: To compare the inflammatory
      reaction associated with the insertion of Krupin silicone, Molteno polypropylene,
      and Acrosof end plates in the subconjunctival space of rabbits. METHODS: Similar
      sized glaucoma end plates made of 3 different biomaterials were sutured to the
      sclera in the superotemporal quadrant of the rabbit eye. Thirty eyes of 15 albino
      New Zealand rabbits were randomly assigned to the 3 groups. Conjunctival vascular
      hyperemia was graded in a masked fashion among the 3 groups. At the end of 3
      weeks, the enucleated eyes were examined histologically and by scanning electron
      microscopy. RESULTS: Molteno polypropylene was associated with more inflammation
      both in clinical observations and based on histological grading. Silicone and
      Acrosof were associated with less intense inflammation. One polypropylene end
      plate was extruded on day 21. CONCLUSIONS: Polypropylene appears to be more
      inflammatory than silicone. Flexible biomaterials appear to be less inflammatory
      than rigid ones. CLINICAL RELEVANCE: Bleb failure following glaucoma drainage
      device implantation could be related to the biomaterial-associated inflammation.
      Choosing a biomaterial with the least inflammatory potential might enhance the
      success rate of the glaucoma drainage device. Arch Ophthalmol. 2000;118:1081-1084

PMID- 10922203
TI  - Neoadjuvant interferon alfa-2b treatment in a murine model for metastatic ocular
      melanoma: a preliminary study.
AB  - OBJECTIVES: To investigate the treatment of metastasis from uveal melanoma and to
      test the effect of interferon (IFN) alfa-2b in a murine model. METHODS: The B16
      LS9 tissue culture melanoma cells were inoculated into the posterior intraocular
      compartment of 3 groups of C57BL/6 mice. The inoculated eyes were enucleated at 9
      days and the mice were euthanized at 26 days after inoculation; the site and
      number of metastases were determined using standard histologic techniques. Group
      1 was the control group; group 2 was given 20,000 international units (IU) of IFN
      alfa-2b intramuscularly 12 hours before enucleation, and group 3 received daily
      injections of 20,000 IU of IFN alfa-2b intramuscularly starting 4 days before
      enucleation. RESULTS: Pulmonary metastases were detected in 57%, 33%, and 0% of
      groups 1, 2, and 3, respectively; hepatic micrometastases were detected only in
      group 1. These results showed a significant decrease in hepatic metastases in
      mice receiving IFN alfa-2b vs controls (P =.005). CONCLUSION: Treatment with IFN
      alfa-2b results in decreased hepatic metastases from intraocular melanoma in a
      murine model. Arch Ophthalmol. 2000;118:1085-1089

PMID- 10922204
TI  - A clinically variant fibrosis syndrome in a Turkish family maps to the CFEOM1
      locus on chromosome 12.
AB  - OBJECTIVES: To describe the phenotype of a Turkish family with variably expressed
      congenital fibrosis of the extraocular muscles (CFEOM), and to determine the
      genetic location of their disorder. METHODS: Participants were examined and had
      blood extracted for genetic analysis. The clinical features of the family's
      disorder were studied, and the disorder was tested for linkage to the 3 known
      CFEOM loci (CFEOM1, CFEOM2, and CFEOM3). RESULTS: Twenty-nine affected and 31
      unaffected family members participated in the study. Eighteen affected
      individuals had congenital bilateral ptosis and restrictive infraductive
      (downward) ophthalmoplegia, consistent with the published descriptions of classic
      CFEOM families linked to the CFEOM1 locus. Eleven affected individuals, however,
      had eye(s) in a neutral primary position, residual upgaze, and/or absence of
      ptosis, thus deviating from previous descriptions of CFEOM1-linked families.
      Analysis of the autosomal dominant variably expressed disorder in this family
      revealed linkage to the CFEOM1 locus on chromosome 12 with a maximum lod score of
      10.8 at D12S85. CONCLUSIONS: This Turkish family segregates a variably expressed
      form of CFEOM that most closely resembles CFEOM3-linked CFEOM, but maps to the
      CFEOM1 locus. CLINICAL RELEVANCE: These data establish that there is much greater
      phenotypic heterogeneity at the CFEOM1 locus than previously reported, and this
      may blur our ability to distinguish the different CFEOM loci based solely on
      clinical presentation. Arch Ophthalmol. 2000;118:1090-1097

PMID- 10922205
TI  - Phenotypic expression of juvenile X-linked retinoschisis in Swedish families with
      different mutations in the XLRS1 gene.
AB  - OBJECTIVE: To describe the clinical phenotype of juvenile X-linked retinoschisis
      in patients with different mutations in the XLRS1 gene. METHODS: Thirty patients
      with 7 different XLRS1 mutations were examined. The genotype was determined by
      molecular genetics, which identified 6 known and 1 novel mutation (exon 5, 489 G-
      >T). Ophthalmologic examination included full-field electroretinogram (ERG)
      recordings. RESULTS: The fundus appearance showed marked variations between, as
      well as within, families with different XLRS1 mutations. The ERG demonstrated
      typical reduction of B-wave amplitude, with relative A-wave preservation, causing
      a reduced B-A ratio in all affected males. The implicit time of the 30-Hz flicker
      ERG was prolonged in all patients examined. In a large family with a deletion of
      exon 1 and the promoter region, 12 affected males showed a phenotype ranging from
      moderate to severe vision impairment and a broad range of ERG abnormality,
      suggesting that additional factors may contribute to the disease severity.
      CONCLUSIONS: Juvenile retinoschisis shows a wide variability in the phenotype
      between, as well as within, families with different genotypes. The ERG findings
      show reduced B-A ratios of dark-adapted recordings and prolonged implicit times
      of 30-Hz flicker response, which provide a useful clinical marker to confirm the
      clinical diagnosis. CLINICAL RELEVANCE: This study describes the wide variability
      in the phenotype in patients with juvenile retinoschisis and different mutations
      in the XLRS1 gene. The study emphasizes the importance of complementing the
      ophthalmologic examination with full-field ERG and molecular genetics in boys
      with visual failure of unknown etiology to determine the diagnosis early in the
      course of the disease. Arch Ophthalmol. 2000;118:1098-1104

PMID- 10922206
TI  - The prevalence of glaucoma in Chinese residents of Singapore: a cross-sectional
      population survey of the Tanjong Pagar district.
AB  - BACKGROUND: Data on prevalence of glaucoma in East Asia are scarce. OBJECTIVE: To
      determine the prevalence and clinical characteristics of glaucoma in adult
      Chinese Singaporeans. METHODS: A group of 2000 Chinese people, aged 40 to 79
      years, were selected from the electoral register of Tanjong Pagar district in
      Singapore using a disproportionate, stratified, clustered, random-sampling
      procedure. Glaucoma was diagnosed in people with an excavated optic neuropathy
      and a reproducible visual field defect or on the basis of severe structural disc
      abnormality alone, if reliable field results could not be obtained. The diagnosis
      was also made in blind subjects with raised intraocular pressure or previous
      glaucoma surgery. RESULTS: Of 1717 eligible subjects, 1232 were examined, with a
      response rate of 71.8%. There were 45 cases of glaucoma: 27 were men and 18 were
      women. The main diagnoses were primary open-angle glaucoma (n = 22 [49%]),
      primary angle-closure glaucoma (n = 14 [31%]), and secondary glaucoma (n = 7
      [16%]). It was not possible to determine the mechanism in 2 (4%). CONCLUSIONS:
      The age-standardized prevalence of glaucoma was 3.2% (95% confidence interval,
      2.3-4.1) in the population 40 years and older. Glaucoma was the leading cause of
      blindness. Primary angle-closure glaucoma and secondary glaucoma were the most
      visually destructive forms of the disease. Our findings suggest current
      projections of glaucoma prevalence among ethnic Chinese are a substantial
      underestimate. Arch Ophthalmol. 2000;118:1105-1111

PMID- 10922207
TI  - A new surgical technique of microkeratome-assisted deep lamellar keratoplasty
      with a hinged flap.
AB  - We describe a new surgical technique of microkeratome-assisted deep lamellar
      keratoplasty for treating patients with corneal stromal disease and normal
      endothelium. A microkeratome is used to create a hinged anterior stromal flap in
      the host cornea, and the diseased stroma is resected or ablated. A complementary
      donor stromal button, prepared using a microkeratome and an artificial anterior
      chamber, is transplanted prior to repositioning of the flap. The flap may be
      lifted at a later date, and an excimer laser used to correct residual refractive
      errors. Notwithstanding the preliminary and theoretical nature of this report,
      this technique may improve the outcomes of deep lamellar keratoplasty and may
      allow for decreased postoperative complications. Arch Ophthalmol. 2000;118:1112
      1115

PMID- 10922208
TI  - Staining of internal limiting membrane in macular hole surgery.
AB  - Removal of internal limiting membranes (ILMs) is a potentially useful surgical
      approach to close an idiopathic macular hole. However, the removal of ILMs is
      difficult to perform because of poor visibility of the ILMs. We have developed a
      technique for staining the ILM with a solution of indocyanine green to facilitate
      the removal of ILMs in eyes with an idiopathic macular hole. Thirteen eyes of 13
      patients (8 women and 5 men, aged from 54 to 68 years) with idiopathical macular
      hole stage 3 or stage 4 that underwent removal of ILMs using this technique had
      an anatomical closure rate of 92% and an improvement of visual acuity of 89%
      (>/=2 Snellen letter chart lines). The excised specimens were evaluated using
      transmission electron microscopy. Our results show that this technique is safe
      and useful in visualizing the ILM, leading to the performance of successful
      removal of an ILM with least damage to the retina. Arch Ophthalmol. 2000;118:1116
      1118

PMID- 10922209
TI  - Emergence of refractive surgery.

PMID- 10922210
TI  - STOP-ROP results suggest selective use of supplemental oxygen for prethreshold
      ROP.

PMID- 10922211
TI  - Mycobacterium szulgai keratitis.

PMID- 10922213
TI  - Corneal melting associated with use of topical nonsteroidal anti-inflammatory
      drugs after ocular surgery.

PMID- 10922212
TI  - Mycobacterium chelonae conjunctivitis and scleritis following vitrectomy.
AB  - The atypical, or nontuberculous, mycobacteria are opportunistic pathogens that
      usually cause infection following accidental trauma or surgery. These organisms
      are ubiquitous in nature but have been found with increasing frequency in other
      environments that include medical offices and surgical suites. Management of
      atypical mycobacterial ocular infections can be difficult because in vitro
      antibiotic activity does not always correlate with in vivo efficacy and because
      normal immune defenses against mycobacteria may work too slowly to prevent
      irreversible damage to infected ocular tissues. This report describes a patient
      who developed a severe ocular infection due to Mycobacterium chelonae after
      vitrectomy. Despite eradication of the infection, the eye became blind and
      painful. Arch Ophthalmol. 2000;118:1125-1128

PMID- 10922215
TI  - Granulomatous local cell reaction to intravitreal silicone.

PMID- 10922214
TI  - A case of suspected alphagan-induced psychosis.

PMID- 10922216
TI  - Treatment of large macular choroidal tubercle improves vision.

PMID- 10922217
TI  - A case of peripapillary staphyloma.

PMID- 10922219
TI  - Patenting medical procedures

PMID- 10922218
TI  - Patenting medical procedures.

PMID- 10922220
TI  - Another cause of uveitis.

PMID- 10922222
TI  - Iridology.

PMID- 10922223
TI  - The cost of juvenile-onset recurrent respiratory papillomatosis.
AB  - OBJECTIVE: To assess the medical costs and the number of quality-adjusted life
      years lost owing to juvenile-onset recurrent respiratory papillomatosis (JORRP).
      DESIGN: We examined hospital and physician charges for JORRP surgical procedures
      in Maryland in 1994 adjusting for inflation and the cost-charge ratio. Centers
      for Disease Control and Prevention data on treatment intensity for JORRP were
      augmented with a review of treatment records for 18 patients with JORRP.
      Sensitivity analyses were performed. To illustrate the application of our cost
      estimates, we compare the costs of JORRP to the costs of the surgical procedures
      that would be necessary to prevent it. RESULTS: We find that the present value at
      birth of the cost of a single case of JORRP is $201,724 (range, $61,822
      $474,334). The annual cost for a single case of JORRP is $57,996 (range, $32,407
      $94,114). The annual cost of JORRP in the United States is between $40 million
      and $123 million depending on the prevalence. Cesarean section (CS) for women
      with condyloma has been suggested as a potential strategy to prevent JORRP, but
      its efficacy remains to be determined. Our results suggest that if only 1% of the
      CSs actually prevented JORRP, this strategy would be a cost-effective means to
      prevent JORRP. CONCLUSIONS: Studies to reduce the uncertainty surrounding the
      efficacy of CS and the effect of both CS and JORRP on families need to precede
      consideration of a policy of CS for women with clinically evident genital
      condyloma. Patients should be kept thoroughly informed about the role of CS for
      the prevention of JORRP and the nature of the remaining uncertainties.

PMID- 10922224
TI  - Confirmations and surprises in the association of tobacco use with sinusitis.
AB  - OBJECTIVE: To generate estimates of sinusitis prevalence for adults in
      association with the use of tobacco or passive smoke exposure. DESIGN: Analysis
      of data from the Third National Health and Nutrition Examination Survey, 1988
      1994. SETTING: Sample of the noninstitutionalized civilian population of the
      United States. PARTICIPANTS: A total of 20,050 adults aged 17 years or older.
      MAIN OUTCOME MEASURE: Presence of self-reported sinusitis or sinus problems.
      RESULTS: In the United States, 66 million adults, constituting 35% of the adult
      population, reported having sinusitis or sinus problems at least once during the
      previous 12 months. Female sex, non-Hispanic white or non-Hispanic black race,
      higher income levels, and progressively higher educational levels were associated
      with increased prevalence of sinusitis. The prevalence of both acute and
      recurrent or chronic sinusitis increased with direct cigarette and other tobacco
      use but did not rise with passive exposure to cigarette smoke. CONCLUSIONS:
      Consistent with data for other respiratory ailments, the direct use of tobacco
      confers a small increased risk of developing sinusitis in the adult population,
      but contrary to expectation, passive smoke does not. The demographic variables of
      sex, race/ethnicity, and educational level demonstrated unexpectedly strong
      associations with the prevalence of sinusitis and should be analyzed and
      controlled for in future studies of sinusitis.

PMID- 10922225
TI  - Microvascular reconstruction and tracheotomy are significant determinants of
      resource utilization in head and neck surgery.
AB  - BACKGROUND: Successful "critical pathway" design and implementation are dependent
      on appropriate patient stratification according to those factors that are primary
      determinants of resource utilization. OBJECTIVES: To test the validity of our
      previously reported critical pathway design and to determine whether tracheotomy
      and microvascular reconstruction (MR) are primary determinants of resource
      utilization. DESIGN: Cost-effectiveness analysis. SETTING: Tertiary referral
      academic institution. METHODS: Retrospective analysis of data from 133 head and
      neck surgery cases in which the treatment regimen was based on critical pathways
      over a 26-month period. OUTCOME MEASURES: Length of stay and total patient
      charges were used as indices of resource utilization. One-way analysis of
      variance and t tests were used for statistical analysis of significance. RESULTS:
      Ninety patients (67.7%) underwent MR; 43 (32. 3%) did not. Seventy-five patients
      (56.4%) underwent tracheotomy; 58 (43.6%) did not. Four patient groups were
      constructed in decreasing order of complexity as follows: group 1, patients who
      underwent both tracheotomy and MR (n = 58); group 2, patients who underwent MR
      alone (n = 32); group 3, patients who underwent tracheotomy alone (n = 17); and
      group 4, patients who did not undergo either procedure (n = 26). Both tracheotomy
      and MR were found to be independent determinants of resource utilization and were
      additive when both were present. The length of stay varied from 8.4 days (in
      patients who underwent both procedures) to 6.7 days (in patients who did not
      undergo either procedure), with intermediate values in cases in which only 1
      procedure was performed. The total charges varied in a similar manner from a high
      of $33,371 to a low of $19,994. Subanalysis with respect to intensive care unit,
      ward, and operating room charges showed a similar stratification. CONCLUSION:
      Tracheotomy and MR are both significant determinants of charges and length of
      stay in head and neck surgery cases and must be considered in the design of
      strategies to promote efficient resource utilization.

PMID- 10922226
TI  - The role of cervical lymphadenectomy after aggressive concomitant
      chemoradiotherapy: the feasibility of selective neck dissection.
AB  - OBJECTIVES: To evaluate the necessity, technical feasibility, and complication
      rate of neck dissection performed on patients with head and neck cancer after 5
      cycles of concomitant chemoradiotherapy (CRT) and to justify a selective neck
      dissection (SND) approach and define the optimal timing of post-CRT neck
      dissection. DESIGN AND SETTING: Retrospective analysis in an academic university
      medical center. PATIENTS: Sixty-nine eligible patients with advanced (stage III
      and IV) head and neck cancer who have undergone 1 of 4 CRT protocols. Patients
      ranged in age from 36 to 75 years, and surgical procedures were performed over a
      4-year period. Follow-up ranged from 6 to 64 months. INTERVENTION: Neck
      dissection (most commonly unilateral SND) performed within 5 to 17 weeks after
      CRT completion. MAIN OUTCOME MEASURES: Complication rate and incidence of
      positive pathology (viable cancer) in pathologic neck dissection specimens.
      RESULTS: Seven (10%) of 69 patients developed wound healing complications, 4 (6%)
      of whom required surgical intervention for ultimate closure. There were no wound
      infections. Other complications occurred in 11 (16%) of 69 patients and included
      need for tracheotomy, nerve transection and paresis, and permanent hypocalcemia.
      Twenty-four (35%) of 69 patients revealed microscopic residual disease. Ten (50%)
      of 20 patients with N3 neck disease had positive pathology, whereas 14 (36%) of
      39 patients with N2 disease had viable carcinoma in the dissection specimen (P
      =.09 by chi(2) analysis). There was no significant relation between radiologic
      complete response or partial response and residual microscopic cancer. In 1
      patient, disease recurred in the neck after dissection. Mean follow-up time was
      30.3 months. CONCLUSIONS: (1) Neck dissection for patients with N2 or greater
      neck disease after CRT is necessary to eradicate residual disease. (2) The
      complication rate of SND after CRT with hyperfractionated radiotherapy is low.
      (3) SNDs are technically feasible when performed within the "window" between the
      acute and chronic CRT injury (4-12 weeks). (4) SNDs, rather than more radical
      procedures, appear to be therapeutically appropriate in this group of patients
      because of the low incidence of disease recurrence in the neck.

PMID- 10922227
TI  - Antisense inhibition of cyclin D1 in human head and neck squamous cell carcinoma.
AB  - OBJECTIVE: To study the role of cyclin D1 in regulating the biological behavior
      of head and neck cancer. DESIGN: Squamous cell carcinoma of the head and neck
      (SCCHN) cells were stably transfected with an antisense cyclin D1 using
      lipofectin-mediated transfection. In vitro growth assays, cell cycle analyses,
      cytotoxicity assays, and in vivo tumorigenicity assays were performed. MATERIALS:
      Human SCCHN cell lines TU138, TU167, TU177, TU182, MDA183, and MDA1386 and
      athymic nude mice were used for this study. RESULTS: The antisense cyclin D1
      transfected cells revealed decreased growth rates in vitro and decreased
      tumorigenicity in athymic nude mice. Furthermore, antisense cyclin D1
      transfection enhanced the chemosensitivity against cisplatin. CONCLUSIONS: These
      studies provided evidence that overexpression of cyclin D1 may play an important
      role in growth rates and biological behavior of human head and neck cancer.
      Additionally, expression of cyclin D1 may make human head and neck cancer cells
      resistant to platinum-based chemotherapeutic approaches. The ability to suppress
      the malignant phenotype by down-regulating cyclin D1 expression may provide a new
      gene therapy approach for patients with head and neck cancer.

PMID- 10922229
TI  - Frequency of cochlear enhancement on magnetic resonance imaging in patients with
      autoimmune sensorineural hearing loss.
AB  - OBJECTIVE: To evaluate magnetic resonance imaging (MRI) scans for enhancement of
      inner ear structures of patients with sensorineural hearing loss and documented
      antibodies to the 68-kd inner ear antigen. STUDY DESIGN: Retrospective case
      review with reexamination of MRI scans. SETTING: Outpatient office. PATIENTS:
      Thirty-five patients with autoimmune sensorineural hearing loss defined by
      audiograms documenting a sensorineural hearing deficit in one or both ears and
      the presence of an anti-inner ear antibody (68-kd band) in serum samples who
      underwent precontrast and postcontrast T1-weighted axial and coronal MRI scans of
      the inner ear, which were performed concurrently with the hearing loss.
      INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Frequency and intensity of
      cochlear enhancement on MRI scans. RESULTS: One patient demonstrated +2 cochlear
      enhancement. However, that finding was thought to represent postoperative
      inflammatory change. CONCLUSION: No correlation was found between the presence of
      antibodies to inner ear antigen in patients with hearing loss and cochlear
      enhancement on MRI scans.

PMID- 10922228
TI  - Auditory brainstem response and magnetic resonance imaging for acoustic neuromas:
      costs by prevalence.
AB  - OBJECTIVE: To compare hypothetical costs for identification of acoustic tumors
      when using magnetic resonance imaging with gadolinium Gd 64 (MRI-(64)Gd) as a
      sole diagnostic test and when using auditory brainstem response (ABR) testing
      followed by MRI-( 64)Gd (ABR + MRI-(64)Gd) for those with positive ABR findings.
      PATIENTS AND METHODS: Retrospective review of the medical records of 75 patients
      having surgically confirmed acoustic neuromas to categorize them into 3 subgroups
      relative to their risk of having a cerebellopontine angle tumor based on history,
      symptoms, and routine pure-tone and speech audiometric findings. Hypothetical
      costs associated with identification of patients with acoustic neuroma in each
      subgroup were calculated for MRI-(64)Gd alone and ABR + MRI-( 64)Gd. Auditory
      brainstem response sensitivity and specificity data for the 75 patients with
      acoustic neuroma and 75 patients without a tumor matched for hearing loss were
      applied to the hypothetical subgroups. Tumor size was considered also. SETTING:
      Tertiary care center. MAIN OUTCOME MEASURE: Comparison of costs for MRI-(64)Gd
      and ABR + MRI-(64)Gd. RESULTS: Fouteen patients with acoustic neuroma were
      assigned to the high-risk category (30% probability); 45 were in the intermediate
      risk category (5% probability); and 16 were in the low-risk category (1%
      probability). Auditory brainstem response testing correctly identified 100% of
      the large tumors (>2.0 cm), 93% of the medium-sized tumors (1.1-2.0 cm), and 82%
      of the small tumors (<1.0 cm). The hypothetical costs for identifying 14 patients
      with acoustic neuroma among 47 patients in the high-risk category using MRI
      (64)Gd would be $70,500; ABR + MRI-(64)Gd costs for the 13 patients identified by
      ABR would be $39,600. Hypothetically 900 patients would be tested to identify the
      45 acoustic neuromas in the intermediate-risk category. Magnetic resonance
      imaging with (64)Gd screening would reach $1.35 million for this sample. Auditory
      brainstem response testing and MRI-(64)Gd would be $486,000, but 4 acoustic
      neuromas would be missed. For the low-risk subgroup MRI-6(4)Gd screening of 1600
      patients to identify 16 acoustic neuromas would total $2.4 million; ABR + MRI
      (64)Gd to identify 15 of them would be $787,500. In this sample of 75 acoustic
      neuromas, large tumors were more prevalent in the low-risk subgroup than in the
      high- or intermediate-risk subgroups. CONCLUSIONS: Decisions regarding assessment
      of patients at risk for acoustic neuromas must be made on a case-by-case basis.
      Use of ABR + MRI-( 64)Gd allows considerable savings when patients are in the
      intermediate- or low-risk subgroups. New MRI and ABR testing techniques offer
      promise for reducing costs.

PMID- 10922230
TI  - Correction of severe caudal deflections with a cartilage "plating" rigid fixation
      graft.
AB  - OBJECTIVE: To evaluate a technique for correction of severe caudal septal
      defects. DESIGN: For all patients, preoperative photographs were analyzed and
      subjective nasal airway patency surveys were conducted. The caudal septal defects
      were then repaired with the cartilage "plating" rigid fixation technique. The
      intraoperative findings were documented in pictorial diagrams. Postoperative
      photographs and repeated airway surveys were obtained during the subsequent
      follow-up visits. Preoperative data and long-term postoperative data were
      compared and analyzed. SETTING: Private practice, ambulatory surgical center.
      PATIENTS: Thirty-six patients had significant caudal septal deviations and
      functional airway obstruction. MAIN OUTCOME MEASURES: Accuracy and stability of
      the correction, airway improvement, patient satisfaction, and morbidity. RESULTS:
      Since 1988, 36 patients were treated for severe caudal septal defects using
      cartilage plating rigid fixation. Follow-up visits have ranged from 3 to more
      than 9 years. All patients have maintained an accurate correction of their caudal
      septal deflections. All patients have also noted subjective improvement of their
      nasal airway. No complication has been encountered. CONCLUSION: Cartilage plating
      rigid fixation seems to be an effective method of correcting the functional
      problems associated with severe caudal septal deformities.

PMID- 10922231
TI  - Computer-aided assessment of bony nasal pyramid dimensions.
AB  - OBJECTIVE: To develop a computer-enabled paradigm for assessment of bony nasal
      pyramid dimensions. DESIGN: Retrospective review of archived computed tomographic
      data. SETTING: Tertiary level academic center. PATIENTS: Patients who had
      undergone computed tomographic scans for computer-aided transsphenoidal
      hypophysectomy were included. Previous nasal surgery, inflammatory sinus disease,
      and documented maxillofacial trauma were exclusion criteria. INTERVENTION:
      Archived computed tomographic scan images were reviewed using the software tools
      on a computer-aided surgical (CAS) system (StealthStation; Sofamor Danek,
      Memphis, Tenn). Standardized methods for the measurement of nasal bone thickness
      and bony nasal pyramid projection were established. MAIN OUTCOME MEASUREMENTS:
      Bony nasal pyramid projection and nasal bone thickness were determined. RESULTS:
      Computed tomographic scans from 8 patients were reviewed. Nasal bone thickness at
      the level of lateral osteotomy was 2.39 +/- 0.68 (mean + SD) mm, while nasal bone
      thickness at the level of intermediate osteotomy was 1.18 + 0.30 mm. Nasal
      projection from the nasomaxillary suture to the rhinion in the axial plane was
      19.20 + 3. 10 (mean + SD) mm, while the corresponding nasal projection at the
      nasion was 20.61 + 3.52 mm. CONCLUSIONS: This brief report presents a new
      paradigm for the assessment of the bony nasal pyramid. Additional normative data
      are necessary. This information has important implications for rhinoplasty
      instrument design, surgical planning, and aesthetic assessment. It is likely that
      computer-enabled review of archived computed tomographic images for maxillofacial
      assessment will become increasingly accepted. Of course, further modifications of
      computer technology and its specific applications are expected.

PMID- 10922232
TI  - Use of internal bioabsorbable PLGA "finger-type" stents in a rabbit tracheal
      reconstruction model.
AB  - OBJECTIVES: To design and develop a biodegradable tracheal stent that can be used
      internally to stabilize and support surgically reconstructed airways. DESIGN: In
      vitro mechanical and degradative properties of 80:20 poly(D,L-lactide-co
      glycolide) (PLGA) "finger-like" stents were determined. The stents were then
      tested in vivo in rabbits that underwent anterior patch tracheoplasties with
      fascia lata grafts. Comparisons were made between a control group and an internal
      stent group for stridor development, overall group mortality, reconstructed
      airway lumen size, and histological findings. SUBJECTS: Twenty-five New Zealand
      white rabbits. RESULTS: The average dry modulus for the internal stents was 6800
      kPa. All of the internal stents cracked by 4 weeks in buffer solution.
      Significant mass loss was not noted in vitro until after 5 weeks in buffer
      solution. By 14 weeks, the stents were nearly 100% degraded. The attrition rate
      for the control group was 23% compared with 17% for the experimental group. The
      stridor rate for the control group was also higher at 38% compared with 17% for
      the stented group. The stented rabbits had a significantly smaller average
      stenosis (23%) across the entire reconstruction site than the control group (34%)
      (P<.05). CONCLUSION: Biodegradable PLGA stents degrade in a predictable fashion
      and have a statistically significant effect in augmenting anterior patch
      tracheoplasties with fascia lata grafts in rabbits.

PMID- 10922233
TI  - Allergen-induced mRNA expression of IL-5, but not of IL-4 and IFN-gamma, in
      peripheral blood mononuclear cells is a key feature of clinical manifestation of
      seasonal allergic rhinitis.
AB  - OBJECTIVES: To investigate the allergen-induced messenger RNA (mRNA) expression
      of interleukin (IL) 4, IL-5 and interferon gamma (IFN-gamma) in peripheral blood
      mononuclear cells from individuals sensitized by Japanese cedar (Cryptomeria
      japonica) pollens, and to elucidate the clinical role of IL-4, IL-5, and IFN
      gamma in the allergen sensitization and clinical manifestation of allergic
      disorders. DESIGN: This study included 30 patients sensitized to the pollen and
      14 nonatopic healthy volunteers. Peripheral blood mononuclear cells (1.0 x 10(6)
      cells/mL) of each individual were cultured at 37 degrees C for 24 hours in the
      presence of 10 microg/mL of Cry j 1, a major allergen of the pollens. Total
      cellular RNA was extracted from the peripheral blood mononuclear cells, and IL-4,
      IL-5, and IFN-gamma mRNA expression was determined with a reverse transcriptase
      polymerase chain reaction. RESULTS: From the results of a survey of symptom diary
      cards and interviews regarding nasal symptoms during the pollen season in 1998,
      we found that 20 patients (symptomatic group), but not 10 patients (asymptomatic
      group), had typical symptoms of seasonal allergic rhinitis. Interleukin 4 mRNA
      was not expressed in the nonatopic subjects but was expressed in 9 asymptomatic
      patients and in 17 symptomatic patients. Interleukin 5 mRNA was exclusively
      expressed in the symptomatic patients. Interferon gamma mRNA expression did not
      differ significantly among the nonatopic subjects, asymptomatic patients, and
      symptomatic patients. CONCLUSIONS: This study has clearly highlighted an
      interesting and new concept that IL-4 is implicated in allergen sensitization but
      not in clinical manifestation, and that IL-5 may not be a feature of atopy in
      itself but seems to be a hallmark of clinical manifestation of ongoing atopic
      diseases.

PMID- 10922234
TI  - Local levels of soluble tumor necrosis factor receptors in patients with allergic
      rhinitis are regulated by amount of antigen.
AB  - OBJECTIVES: To examine the possible correlation between the amount of antigen and
      the level of soluble tumor necrosis factor receptor (sTNFR), and to assess its
      biologic significance in allergic reactions. DESIGN: Randomized control trial.
      SUBJECTS: Twelve volunteers with Japanese cedar pollinosis and 10 healthy
      volunteers. INTERVENTIONS: The levels of p55 sTNFR (sTNFR1) and p75 sTNFR
      (sTNFR2) in samples of serum and nasal epithelial lining fluid (ELF) from 12
      subjects with pollinosis and 10 healthy subjects were measured 4 times
      (preseason, early season, midseason, and postseason) in low (total, 415/cm( 2)
      per season) and high (total, 19,935/cm(2) per season) pollen-count periods, and
      the results were compared among the 4 groups. RESULTS: In the low-pollen-count
      period, increased levels of sTNFR1 and sTNFR2 were observed in ELF samples from
      the allergic subjects during the midseason. In contrast, in the high-pollen-count
      period, those levels were already elevated during the preseason and reduced
      during the midseason. Especially, the levels of sTNFR2 in ELF samples from the
      allergic subjects during the midseason in the high-pollen-count period were
      significantly lower than those in the low-pollen-count period. Moreover, a
      significant negative correlation (sTNFR1, R = -0.82; sTNFR2, R = -0. 73) was
      found between the levels of sTNFR1 and sTNFR2 in ELF samples and the scores of
      symptoms in the allergic subjects in the high-pollen-count period, but not in the
      low-pollen-count period. CONCLUSION: In patients with pollinosis, the amounts of
      antigen regulate the local levels of sTNFRs, possibly inhibiting nasal allergic
      inflammation.

PMID- 10922235
TI  - Le Fort I osteotomy and skull base tumors: a pediatric experience.
AB  - BACKGROUND: The Le Fort I maxillary osteotomy approach for skull base tumor
      removal in the pediatric age group has not been widely discussed in the
      literature except for sporadic case reports and limited case series. OBJECTIVES:
      To review our experience with the Le Fort I osteotomy and to propose that it be
      used as an alternative approach because of its many advantages for the removal of
      tumors of the central skull base and paranasal sinuses. DESIGN: Case series.
      SETTING: Tertiary academic center. PATIENTS AND METHODS: A 5-year retrospective
      chart review of cases involving children who had undergone skull base tumor
      resection via the Le Fort I osteotomy approach. INTERVENTIONS: Skull base tumor
      removal via the Le Fort I osteotomy approach. MAIN OUTCOME MEASURES: Tumor type,
      location, and size; intraoperative and postoperative complications; and residual
      tumor and/or tumor recurrence associated with the surgical approach. RESULTS:
      Eleven patients (9 boys and 2 girls; mean age, 14.3 years) were identified
      through the chart review. The tumor types included 8 angiofibromas, 1 malignant
      fibrous histiocytoma, 1 giant cell tumor, and 1 cavernous hemangioma. All these
      lesions had extensive tumor growth into at least 1 of the following sites:
      pterygomaxillary space, sphenoidal sinus, and areas adjacent to the optic nerve,
      cavernous sinus, clivus, and anterior cranial fossa. The mean follow-up for this
      cohort was 12.8 months. No intraoperative complications were noted. Postoperative
      complications were reviewed with respect to the approach. To date, there have
      been no cases of residual tumor or tumor recurrence that can be attributed to the
      procedure. CONCLUSIONS: Our experience suggests that the Le Fort I osteotomy
      approach is a useful technique for the removal of extensive central skull base
      tumors and paranasal sinuses in the pediatric age group. It has distinct
      advantages over traditional anterior or lateral approaches, including a more
      direct line of vision and improved exposure and cosmesis.

PMID- 10922236
TI  - In vitro bacterial interference in the nasopharynx of otitis media-prone and non
      otitis media-prone children.
AB  - OBJECTIVE: To compare the frequency of recovery of potential pathogens and
      aerobic- and anaerobic-interfering bacteria in the nasopharynx of otitis media
      prone (OMP) with that in non-OMP (N-OMP) children. PATIENTS AND METHODS:
      Nasopharyngeal cultures were obtained from 20 OMP and 20 N-OMP children.
      Potential pathogens and aerobic and anaerobic bacteria with interfering
      capabilities against these organisms were identified. RESULTS: Eighteen potential
      pathogens were isolated from 12 of the 20 OMP children, and 9 were recovered from
      5 of the 20 N-OMP children (P<.05). Fifty-eight aerobic and anaerobic isolates
      with interfering capability against 4 potential pathogens were recovered from 5
      of the OMP group, and 139 from 17 of the N-OMP group (P<.05). These interfering
      organisms included alphahemolytic streptococci, nonhemolytic streptococci,
      Prevotella species, and Peptostreptococcus species. CONCLUSION: The
      nasopharyngeal flora of N-OMP children contains more aerobic and anaerobic
      organisms with interfering capability and less potential pathogens than that of
      OMP children.

PMID- 10922237
TI  - Delayed-onset sensorineural hearing loss in a 3-year-old survivor of persistent
      pulmonary hypertension of the newborn.
AB  - Persistent pulmonary hypertension of the newborn (PPHN) and its conventional
      medical treatment are associated with sensorineural hearing loss, yet current
      recommendations for regular audiological evaluations of PPHN survivors are
      lacking. We report a case of delayed-onset, progressive sensorineural hearing
      loss in a 3-year-old patient with a history of PPHN and a normal auditory
      brainstem evoked response at 6 weeks of age. The relatively late detection of
      significant sensorineural hearing loss in this otherwise healthy 3-year-old
      illustrates the need for audiological evaluation at regular intervals in patients
      with a history of PPHN.

PMID- 10922238
TI  - Histopathologic features of the temporal bone in usher syndrome type I.
AB  - Temporal bones of 2 patients with Usher syndrome type I were examined using light
      microscopy. In both patients, findings from histopathologic examination of the
      cochlea were characterized by degeneration of the organ of Corti, which was most
      marked in the basal turn, atrophy of the stria vascularis, and a decrease in the
      number of spiral ganglion cells. The cochlear nerve appeared to be diminished.
      The sensory epithelium of the saccular and utricular maculae of patient 1 was
      normal for age. The left temporal bone of patient 2, classified as Usher syndrome
      genetic subtype USH1D or USH1F, demonstrated the typical signs of severe
      cochleosaccular degeneration. Present cases and cases from the literature were
      reviewed in search of an explanation for the above-described differences in
      histologic findings.

PMID- 10922239
TI  - Sudden unilateral hearing loss with simultaneous ipsilateral posterior
      semicircular canal benign paroxysmal positional vertigo: a variant of vestibulo
      cochlear neurolabyrinthitis?
AB  - We describe 4 patients who all simultaneously developed a sudden total or partial
      unilateral sensorineural hearing loss and an unusual acute peripheral
      vestibulopathy in the same ear characterized by posterior semicircular canal
      benign paroxysmal positional vertigo with intact lateral semicircular canal
      function. Two patients also had ipsilateral loss of otolith function. The vertigo
      resolved in all 4 patients after particle-repositioning maneuvers. The findings
      of audiometry and vestibular tests indicated that the lesion responsible for this
      syndrome was probably located within the labyrinth itself rather than within the
      vestibulocochlear nerve and that it was more likely a viral vestibulocochlear
      neurolabyrinthitis than a labyrinthine infarction.

PMID- 10922240
TI  - Radiology forum: imaging quiz case 1. Hemifacial spasm (HFS) due to an enlarged
      basilar artery compressing the right seventh cranial nerve (basilar artery
      dolichoectasia).

PMID- 10922241
TI  - Radiology forum: imaging quiz case 2. Calcific tendinitis of the longus colli
      muscle.

PMID- 10922242
TI  - Radiology forum: imaging quiz case 3. Hamartoma of the nasopharynx.

PMID- 10922243
TI  - Radiology forum: imaging quiz case 4. Giant osteoma of the mandible.

PMID- 10922244
TI  - Pediatric tympanoplasty and the role of preoperative eustachian tube evaluation.

PMID- 10922245
TI  - There are no accurate tests for eustachian tube function.

PMID- 10922246
TI  - Tasting instilled otologic drops is not a reliable test of eustachian tube
      function.

PMID- 10922247
TI  - "The cutting edge": F. William Blaisdell, MD.

PMID- 10922248
TI  - Long-term results of reoperation and localizing studies in patients with
      persistent or recurrent medullary thyroid cancer.
AB  - HYPOTHESIS: Reoperation benefits patients with locoregional, persistent, or
      recurrent medullary thyroid cancer (MTC). Currently available localizing studies
      have limited utility for detecting all foci of residual MTC. DESIGN: A
      retrospective study with a mean follow-up time of 7.5 years (median, 13 years;
      range, 2.2-29 years). SETTING: A tertiary referral medical center. PATIENTS:
      Thirty-three patients who underwent 46 reoperations for locoregional residual
      MTC. RESULTS: Sixty-four percent of residual MTC was located in the lateral
      cervical nodes, 22% in the central cervical nodes or thyroid bed, and 14% in the
      anterior mediastinum (197 of 1128 nodes resected were positive for MTC). After
      reoperation, basal calcitonin levels were undetectable in 2 patients, reduced by
      greater than 50% in 10 patients, and either increased or were not reduced by
      greater than 50% in the remaining patients. On reoperation, one patient had a
      thoracic duct injury that required reexploration and ligation. Patients who had a
      greater than 50% decrease in calcitonin levels after reoperation were less likely
      to develop distant metastases compared with patients who did not have a greater
      than 50% decrease (P<.05). The sensitivities of magnetic resonance imaging (n =
      31), computed tomographic scan (n = 16), ultrasound (n = 9), and
      dimercaptosuccinic acid scan (n = 3) were 91%, 86%, 88%, and 100%, respectively.
      CONCLUSIONS: Although reoperation in patients with residual MTC rarely results in
      biochemical cure, cervical reexploration is safe and in selected patients may
      limit MTC progression. Lateral cervical node dissection could be beneficial at
      the time of initial surgical treatment because of the high frequency of residual
      MTC in the lateral cervical nodes. Noninvasive imaging studies were helpful but
      far from perfect for guiding the reexploration for locoregional residual MTC.

PMID- 10922249
TI  - Laparoscopic heller myotomy and anterior fundoplication for achalasia results in
      a high degree of patient satisfaction.
AB  - HYPOTHESIS: Laparoscopic Heller myotomy with anterior fundoplication will
      alleviate the symptoms of achalasia and result in excellent patient satisfaction.
      DESIGN: Retrospective study of consecutive patients who underwent laparoscopic
      Heller myotomy with anterior fundoplication for achalasia between October 1995
      and July 1999. A telephone survey assessed symptoms and satisfaction. Patients
      were asked to quantitate their symptoms on a scale of 0 to 3 (0 = none; 1, mild;
      2, moderate; and 3, severe). SETTING: University referral center. PATIENTS:
      Twenty-four patients who underwent laparoscopic Heller myotomy with anterior
      fundoplication for achalasia. MAIN OUTCOME MEASURES: Postoperative symptoms and
      satisfaction. RESULTS: Twenty-one patients (88%) were successfully contacted.
      Mean follow-up was 16.5 months. The laparoscopic approach was successful in all
      but 3(88%). The mean dysphagia score was 2.81 preoperatively and 0.81
      postoperatively (P<.000). The mean chest pain score was 1. 57 preoperatively and
      0.86 postoperatively (P<.015). The mean supine regurgitation score was 2.10
      preoperatively and 0.57 postoperatively (P<.000). The mean upright regurgitation
      score was 1.57 preoperatively and 0.52 postoperatively (P<.000). The mean
      heartburn score was 1.57 preoperatively and 0.57 postoperatively (P<.000).
      Postoperatively, 18 (86%) of 21 patients could swallow bread without difficulty
      and 17 (89%) of 19 patients could eat meat without difficulty (2 were excluded as
      they were vegetarians). Twenty (95%) of 21 patients reported improvement after
      the operation. CONCLUSIONS: Laparoscopic Heller myotomy with anterior
      fundoplication significantly relieves the symptoms of achalasia without causing
      the symptoms of gastroesophageal reflux disease. This procedure results in
      excellent overall patient satisfaction.

PMID- 10922250
TI  - Rational treatment of empyema in children.
AB  - HYPOTHESIS: Efficacious and cost-effective treatment of pediatric empyema can be
      accomplished following a protocol based on its radiographic appearance.
      Therapeutic modalities include thoracostomy tube drainage (TTD) with or without
      fibrinolytic therapy (FT) and video-assisted thoracoscopic debridement (VATD).
      DESIGN: Retrospective case series. SETTING: Tertiary referral center. RESULTS:
      From 1995 through 1999, 31 children were treated ranging in age from 11 months to
      18 years (mean age, 5.1 years). Twenty-seven (87.1%) underwent TTD; of these, 22
      (81.5%) received FT with urokinase. The TTD failed in 4 children (14.8%) who
      required salvage VATD. Primary VATD was performed in another 4 children (12.9%).
      The mean length of stay was 14.6 days (TTD, 14.1 days; salvage VATD, 20. 0 days;
      primary VATD, 11.5 days), ranging from 8.0 to 30.0 days. Complications included
      readmission for fever (2 patients [6.5%]) and gastrointestinal bleeding (1
      patient [3.2%]). There were no anaphylactic reactions or bleeding episodes due to
      urokinase. Two patients (7.4%) treated with TTD and FT developed an air leak that
      resolved spontaneously. The mean hospital charges were $78,832 (TTD with or
      without FT, $75,450; salvage VATD, $107,476; primary VATD, $69,634). The
      procedural charges were highest for salvage VATD. CONCLUSIONS: Most cases of
      pediatric empyema can be treated by TTD with or without FT. This therapy is safe
      and effective for children with nascent disease. Primary VATD is preferred in
      children with advanced disease. Cost-effectiveness could be further improved
      through better prediction of those patients likely to fail TTD and require
      salvage VATD. An algorithmic approach based on findings from computed tomography
      or (better) ultrasonography of the chest may be the best way to make this
      distinction and rationalize care.

PMID- 10922252
TI  - Invited critique: repair of traumatic aortic rupture

PMID- 10922251
TI  - Repair of traumatic aortic rupture: a 25-year experience.
AB  - BACKGROUND: Surgical management of traumatic aortic rupture (TAR) is
      controversial, specifically whether distal aortic perfusion modifies the outcome.
      HYPOTHESIS: The outcome of patients who undergo repair of TAR is not dependent on
      the technique of repair. DESIGN: Retrospective review. SETTING: Tertiary care
      teaching hospital, level I regional trauma center. PATIENTS: One hundred fifteen
      victims (aged 5-81 years) of blunt chest trauma with aortic tear, presenting
      between January 1, 1974, and June 30, 1999. METHODS: Medical records were
      reviewed for prehospital and emergency department data, operative findings, and
      outcome. Statistical comparison was made using a paired 2-tailed t test.
      INTERVENTION: Surgical repair of TAR with (group 1) or without (group 2) distal
      aortic perfusion. RESULTS: Thirty-two patients in group 1 had TAR repair using
      active bypass (n = 18) or Gott shunt (n = 14). The clamp-and-sew technique was
      used in 83 patients (group 2). Primary repair was possible in 14 patients (44%)
      in group 1 and 69 patients (83%) in group 2. The average aortic cross-clamp time
      was 48 minutes for group 1 (range, 25-113 minutes) and 20 minutes for group 2
      (range, 5-40 minutes) (P<.03). There was no significant difference in hospital
      mortality (6 [18.7%] of 32 vs 15 [18.1%] of 83) or the incidence of paraplegia (2
      [6%] of 32 vs 5 [6%] of 83) between groups 1 and 2. During the last 15 years, 78
      patients (73 in group 2) had repair of TAR with an operative mortality rate of
      19.2%. CONCLUSIONS: Acute TAR remains a highly lethal injury with no change in
      prognosis during the last 2(1/2) decades. Repair of TAR using simple aortic cross
      clamping alone is feasible in the majority of patients without increased
      mortality or spinal cord injury.

PMID- 10922253
TI  - Comparison of minimally invasive esophagectomy with transthoracic and transhiatal
      esophagectomy.
AB  - HYPOTHESIS: Minimally invasive esophagectomy can be performed as safely as
      conventional esophagectomy and has distinct perioperative outcome advantages.
      DESIGN: A retrospective comparison of 3 methods of esophagectomy: minimally
      invasive, transthoracic, and blunt transhiatal. SETTING: University medical
      center. PATIENTS: Eighteen consecutive patients underwent combined thoracoscopic
      and laparoscopic esophagectomy from October 9, 1998, through January 19, 2000.
      These patients were compared with 16 patients who underwent transthoracic
      esophagectomy and 20 patients who underwent blunt transhiatal esophagectomy from
      June 1, 1993, through August 5, 1998. MAIN OUTCOME MEASURES: Operative time,
      amount of blood loss, number of operative transfusions, length of intensive care
      and hospital stays, complications, and mortality. RESULTS: Patients who had
      minimally invasive esophagectomy had shorter operative times, less blood loss,
      fewer transfusions, and shortened intensive care unit and hospital courses than
      patients who underwent transthoracic or blunt transhiatal esophagectomy. There
      was no significant difference in the incidence of anastomotic leak or respiratory
      complications among the 3 groups. CONCLUSION: Minimally invasive esophagectomy is
      safe and provides clinical advantages compared with transthoracic and blunt
      transhiatal esophagectomy.

PMID- 10922254
TI  - Lymphatic mapping and focused analysis of sentinel lymph nodes upstage
      gastrointestinal neoplasms.
AB  - BACKGROUND: Lymph node analysis is essential for staging gastrointestinal (GI)
      neoplasms. Intraoperative lymphatic mapping and sentinel lymphadenectomy were
      originally described for melanoma but have not yet been investigated for most GI
      neoplasms. HYPOTHESES: (1) Lymphatic mapping and sentinel lymphadenectomy is
      feasible in GI neoplasms, (2) the sentinel node (SN) status reflects the regional
      node status, and (3) focused analysis of the SN improves staging accuracy.
      DESIGN: Prospective patient series. PATIENTS AND METHODS: Lymphatic mapping was
      performed in 65 patients with GI neoplasms by injecting 0.5 to 1 mL of isosulfan
      blue dye around the periphery of the neoplasm. Blue-stained SNs were analyzed by
      hematoxylin-eosin staining, multiple sectioning, and cytokeratin
      immunohistochemistry. RESULTS: Lymphatic mapping identified at least 1 SN in 62
      patients (95%). Of the 36 cases with nodal metastasis, 32 (89%) had at least 1
      positive SN and 15 (42%) had nodal metastasis only in the SN. In 11 cases, tumor
      deposits were identified by multiple sectioning (n = 2) or immunohistochemistry
      (n = 9) only. In 5 cases (8%), lymphatic mapping identified aberrant lymphatic
      drainage that altered the extent of the lymphadenectomy. CONCLUSIONS: Lymphatic
      mapping and sentinel lymphadenectomy are feasible in GI neoplasms and identify
      aberrant lymphatic drainage. The SN status accurately reflects the regional node
      status. Focused analysis of the SN increases the detection of micrometastases and
      may improve selection of patients for adjuvant treatment.

PMID- 10922255
TI  - Laparoscopic ultrasound vs triphasic computed tomography for detecting liver
      tumors.
AB  - BACKGROUND: Accurate staging of malignant tumors in the liver has major
      implications in defining prognosis and guiding both surgical and nonsurgical
      therapy. Intraoperative ultrasound in open surgery compares favorably with
      computed tomography (CT) in the detection of liver tumors; however, there is
      little experience with laparoscopic ultrasound (LUS). HYPOTHESIS: Laparoscopic
      ultrasound is more sensitive than triphasic CT for detecting primary and
      metastatic liver tumors. DESIGN: Prospective study. SETTING: University hospital.
      PATIENTS: Fifty-five patients with a total of 222 lesions, including primary and
      metastatic liver tumors, who underwent both CT examinations and LUS as a part of
      a tumor ablation procedure. INTERVENTIONS: Triphasic spiral CT scans of the liver
      were obtained within 1 week before surgery. Liver LUS was performed with a linear
      7.5-MHz side-viewing laparoscopic transducer. RESULTS: The LUS detected all 201
      tumors seen on preoperative CT and detected 21 additional tumors (9.5%) in 11
      patients (20.0%). These tumors missed by CT ranged in size from 0.3 to 2.7 cm.
      Smaller tumors tended to be missed by CT scan (28.6% of the lesions <1 cm, 15.8%
      of those 1-2 cm, 4% of those 2-3 cm, and 0% of those >3 cm), as did those in
      segments III and IV. There was good correlation between the size of lesions
      imaged by the 2 modalities (Pearson r = 0.86; P<.001). CONCLUSION: Laparoscopic
      ultrasound offers increased sensitivity over CT for the detection of liver
      tumors, especially for smaller lesions. This study documents the ability of LUS
      in detecting liver tumors and argues for more widespread use in laparoscopic
      staging procedures.

PMID- 10922256
TI  - Institutional peer review can reduce the risk and cost of carotid endarterectomy.
AB  - HYPOTHESIS: Surgeon-directed institutional peer review, associated with positive
      physician feedback, can decrease the morbidity and mortality rates associated
      with carotid endarterectomy. DESIGN: Case series. SETTING: Tertiary care
      university teaching hospital. PATIENTS/INTERVENTIONS: All patients undergoing
      carotid endarterectomy at our institution during a 5-year period ending August
      1998. RESULTS: Stroke rate decreased from 3.8% (1993-1994) to 0% (1997-1998). The
      mortality rate decreased from 2.8% (1993-1994) to 0% (1997-1998). Length of stay
      decreased from 4.7 days (1993-1994) to 2.6 days (1997-1998). The total cost
      decreased from $13,344 (1993-1994) to $9548 (1997-1998). CONCLUSIONS: An
      objective, confidential peer review process that provides ongoing feedback of
      performance to surgeons and documents that performance in relationship with that
      of peers seems to be effective in reducing the morbidity and mortality rate
      associated with carotid endarterectomy. In addition, the review process lowered
      the hospital cost of performing carotid endarterectomy.

PMID- 10922257
TI  - Is laparoscopic donor nephrectomy the new criterion standard?
AB  - HYPOTHESIS: The posttransplantation renal function outcomes between consecutive
      open donor and laparoscopic donor nephrectomies (LDNs) are similar and affect
      living donation. DESIGN: Using the medical records of renal living donor
      recipient pairs, 36 consecutive open donor nephrectomies were compared with the
      subsequent 100 LDNs. Data collected on donor characteristics included
      demographics (age, race, sex, weight, and height), renal vascular and ureteral
      anatomical features, surgical information (blood loss, number of blood
      transfusions, operating time, warm ischemia time, and renal injury),
      complications, and length of hospital stay. Recipients' data also included renal
      function information (serum creatinine level on postoperative days 7 and 30) and
      ureteral complications during the initial hospital stay. SETTING: A not-for
      profit tertiary care teaching hospital in a metropolitan area. PATIENTS: Adults
      who had end-stage renal disease and received a living donation kidney. MAIN
      OUTCOME MEASURES: Operative time, warm ischemia time, blood loss, and
      posttransplantation serum creatinine level. RESULTS: Patient characteristics were
      not significantly different between the open donor nephrectomy and LDN groups. No
      right kidney LDNs were done because of the shortness of the right renal vein;
      and, after the initial experience, left kidneys with more than 2 arteries were
      excluded. Warm ischemia time was recorded only for LDN, and it was found that a
      warm ischemia time of 10 minutes or longer was associated with difficulty in
      extraction and was uniformly associated with elevated mean serum creatinine
      levels on postoperative day 7. CONCLUSIONS: The length of hospital stay was
      decreased and cosmetic result enhanced. The number of living donors has increased
      from 28 in 1997 to 53 in 1998 and to 63 in 1999 at our institution. The length of
      hospital stay, incidence of complications, and comparable kidney quality indicate
      that LDN should be the initiating procedure for most patients.

PMID- 10922259
TI  - Decreased systemic polymorphonuclear neutrophil (PMN) rolling without increased
      PMN adhesion in peritonitis at remote sites.
AB  - BACKGROUND: Previous in vitro studies have demonstrated that the host response to
      intra-abdominal infection produces increased generalized polymorphonuclear
      neutrophil (PMN) adherence to vascular endothelial cells (ECs), which may lead to
      subsequent endothelial damage, leaky capillaries, and organ dysfunction. There
      are scant data to demonstrate this enhanced systemic PMN adherence in vivo or the
      influence of PMN rolling on PMN endothelial adherence. HYPOTHESIS: Systemic PMN
      adherence in the animal with sepsis is increased. DESIGN: In vivo murine model of
      a 2-front infection using intravital microscopy of the cremasteric muscle to
      quantify PMN-EC adherence in a septic response. SETTING: Basic science laboratory
      and animal surgical facility. PATIENTS OR OTHER PARTICIPANTS: One hundred CD1
      male mice. INTERVENTIONS: Animals underwent cecal ligation and puncture
      peritonitis, cremasteric muscle Escherichia coli infection, both infections, or
      neither (controls). Eighteen hours later, the mice underwent exteriorization of
      the cremasteric muscle under an intravital microscope for measurement of PMN-EC
      interactions. Blood was then drawn for calculation of circulating PMN counts.
      MAIN OUTCOME MEASURES: Adherence of PMNs, PMN rolling flux, PMN rolling velocity,
      and circulating PMN counts. RESULTS: Circulatory mechanics did not differ between
      the groups. Unlike static in vitro systems, we could not detect an increase in
      PMN adherence after peritonitis with this dynamic in vivo model. A local
      (cremasteric) infection was associated with marked PMN adherence. Peritonitis was
      associated with reduced PMN adherence at a local infection site as well as
      reduced rolling adhesion and PMN rolling velocity. CONCLUSIONS: The data suggest
      that intra-abdominal infection does not increase remote PMN adherence, and may
      actually result in reduction of systemic adherence via modulation of PMN rolling.

PMID- 10922258
TI  - Wound recurrences following laparoscopic-assisted colectomy for cancer.
AB  - OBJECTIVES: To determine the incidence and clinical relevance of wound
      recurrences (WRs) following laparoscopic-assisted colectomy for cancer; to
      analyze the most recent experimental studies examining possible pathogenic
      mechanisms; and to delineate possible prevention strategies. DATA SOURCES: A
      MEDLINE search was conducted using the words "colectomy," "laparoscopy," and
      "recurrence, local." Additional articles were retrieved by cross-referencing.
      STUDY SELECTION: All clinical and experimental studies retrieved were reviewed
      and subjectively selected according to their relevance for clinical practice.
      DATA EXTRACTION: Clinical data from 1990 to 2000 with series analyzing 50 or more
      patients were preferentially considered. Experimental data were considered based
      on the most rigorous study designs and the potential impact of experimental
      findings on clinical practice. DATA SYNTHESIS: The incidence of WRs in large
      series and based on current techniques is comparable to what has been reported
      for WR following open colectomy. While the pathogenesis of early WR occurrences
      remains unclear, experience and appropriate training in laparoscopic-assisted
      colectomy are essential to minimize the incidence of WRs. Results from
      experimental studies are still controversial, and available data from prospective
      randomized clinical trials are still limited. CONCLUSIONS: Results from
      prospective randomized trials are needed to provide definitive answers regarding
      the incidence and survival impact of WRs. Until then, WR may be considered a
      technical complication following laparoscopic-assisted colectomy.

PMID- 10922260
TI  - Laparoscopic posterior adrenalectomy: technical considerations.
AB  - HYPOTHESIS: Although laparoscopic posterior adrenalectomy (LPA) offers a more
      direct access to the adrenal gland, it is not as popular as laparoscopic
      transabdominal adrenalectomy, and the worldwide experience has been limited. We
      hypothesized that LPA is a safe and efficacious procedure that could best serve
      certain patients with adrenal tumors. DESIGN: Case series of patients undergoing
      laparoscopic adrenalectomy in a single institution. SETTING: University teaching
      hospital. PATIENTS: Medical records of 31 patients with 33 tumors who underwent
      LPA were reviewed. Indications for operation included hormone secretion in 23
      patients (74%), suspected or known malignant neoplasms in 7 patients (23%), and
      local symptoms in 1 patient (3%). INTERVENTION: The LPAs were performed with the
      patients in prone position. Preoperative ultrasonography localized the adrenal
      tumor and kidney to guide balloon trocar placement for the creation of a working
      retroperitoneal space. The LPAs were performed with three 10-mm trocars using
      laparoscopic ultrasound to localize the tumor and the harmonic scalpel to perform
      the dissection. MAIN OUTCOME MEASURES: Demographic data, type and size of tumor,
      operative time, blood loss, intraoperative and postoperative complications, and
      hospital stay were analyzed. RESULTS: All operations were successfully completed
      without conversion. Excluding the bilateral cases, the mean +/- SD operative time
      was 176 +/- 104 minutes. Estimated blood loss averaged 32 mL (range, 10-200 mL).
      There were no intraoperative complications. The mean +/- SD tumor size was 3.2 +/
      1.8 cm (range, 0.8-7.0 cm). Pathological evaluation revealed benign tumors in 25
      patients (81%) and malignant tumors in 6 patients. The average hospital stay was
      1.4 days (range, 1-3 days). There were no deaths. CONCLUSIONS: Although
      technically more demanding, LPA should be considered in patients with tumors less
      than 6 cm, bilateral tumors, or extensive previous abdominal surgery.

PMID- 10922261
TI  - Perceived obstacles to career success for women in academic surgery.
AB  - HYPOTHESIS: We conducted this study to determine whether concerns expressed by
      male and female surgeons at 1 academic center are generally reflective of broader
      concerns for academic surgery and academic medicine. We reviewed published
      studies concerning women in academic surgery within the context of reporting the
      results of a survey of both male and female surgeons at 1 academic center. DATA
      SOURCES: We developed a survey that included demographic information, work
      experience, and social issues. The survey was distributed to the entire faculty.
      For key questions, we compared answers between male and female faculty.
      Additional data came from the published literature. STUDY SELECTION: We reviewed
      all available studies identified by a MEDLINE search with key words women and
      academic and medicine or physician. Included studies contained either data
      collection or editorial comment concerning women in academic medicine. DATA
      EXTRACTION: Data and opinions from all included studies paralleling survey
      questions were extracted from each article. DATA SYNTHESIS: Male and female
      faculty members reported different experiences and perceptions, specifically
      relating to relationships between family and professional life and perceptions of
      subtle sex-related biases. Both men and women reported insufficient mentoring and
      difficulties in balancing personal and professional responsibilities.
      CONCLUSIONS: Attitudes, behaviors, and traditions surrounding how we structure
      work and evaluate participation in academic surgery are more difficult to change
      than just addressing obvious inequities in support for female surgeons. However,
      attempting the deeper changes is worthwhile, because addressing obstacles faced
      by female faculty, many of which also affect men, will allow progress toward
      environments that attract and retain the best physicians, regardless of sex.

PMID- 10922264
TI  - Invited critique: glove leakage rates as a function of latex content and brand

PMID- 10922262
TI  - Long-term results of surgery for liver hemangiomas.
AB  - BACKGROUND: Elective surgery for liver hemangiomas is still controversial.
      HYPOTHESIS: Long-term results show that elective surgery for liver hemangiomas is
      safe and effective. SETTING: A tertiary care university hospital in Istanbul,
      Turkey. PATIENTS: Forty-two patients underwent surgery for liver hemangiomas
      between January 1988 and December 1998; 41 were symptomatic. The primary
      indications for surgery were abdominal pain in 33 patients, diagnostic
      uncertainty in 6, and enlargement in 3. The median largest dimension of the major
      lesion was 10 cm (range, 7-45 cm). MAIN OUTCOME MEASURES: (1) Patients'
      assessment of the effects of surgery on preoperative symptoms, (2) determination
      of whether any other pathological conditions were missed in the preoperative
      evaluation, (3) operative mortality and morbidity, and (4) recurrences. DESIGN:
      Retrospective cohort study. RESULTS: Enucleation was the most frequent operation
      (33 patients). Hospital mortality and morbidity were 2.4% (bleeding from the
      biopsy site on a lesion evaluated as inoperable at laparotomy; 1 patient) and 12%
      (5 patients), respectively. Thirty-three patients could be followed up for a
      median of 53 months (range, 6-135 months). Of the 32 preoperatively symptomatic
      patients, surgery was successful in symptom control in 28 (88%) (complete
      resolution or significant amelioration). No other cause of pain could be
      identified during follow-up in the other patients. Control ultrasonography
      revealed no recurrences. CONCLUSIONS: Elective surgery is indicated in a small
      subset of patients with hemangiomas because of abdominal pain, enlargement, and
      diagnostic uncertainty. The results of surgery in symptom control are gratifying
      in approximately 90% of patients. Recurrences are rare. Enucleation can be
      performed rapidly and safely in most patients and should be preferred to
      resection.

PMID- 10922263
TI  - Glove leakage rates as a function of latex content and brand: caveat emptor.
AB  - HYPOTHESIS: That water leakage rates and protection against blood-borne pathogens
      should not vary as a function of latex content among Food and Drug Administration
      approved gloves, allowing avoidance of unnecessary latex exposure. DESIGN AND
      METHODS: Eighteen different glove types were purchased and tested using the
      American Society for Testing Methods Standard Test for Detecting Holes in medical
      gloves, which involves mounting the glove on a plastic tube, pouring a liter of
      tap water into the glove, and visually inspecting the glove initially and after 2
      minutes. Half of the gloves were tested straight from the package and half after
      a standardized manipulation. SETTING: A university hospital. RESULTS: Eleven
      sterile glove types (5 high latex content, 4 low latex content, and 2 nonlatex
      content), and 7 nonsterile examination glove types (2 high latex content, 2 low
      latex content, and 3 nonlatex content) were tested (total tested, 3720 gloves).
      Leakage rates were greater for examination than for surgical gloves (relative
      risk [RR], 1.41, 95% confidence interval [CI], 1.01-1.96), for manipulated than
      for unused gloves (RR, 2.89, 5% CI, 1.98-4.22), and for low latex content
      surgical gloves (RR, 2.58, 95% CI, 1.35-4.92) or nonlatex content surgical gloves
      (RR, 4.93, 95% CI, 2.35-10.32) than for high latex content surgical gloves.
      Significant differences were observed among low latex content surgical gloves
      (P</=.001) and all types of examination gloves (P =.0015) especially after the
      standardized manipulation (leakage rates ranging from 0%-30%). CONCLUSIONS: Food
      and Drug Administration approval should not be interpreted as suggesting equality
      of different manufacturers' products. Some low latex and nonlatex content gloves
      are very resistant to leakage and should provide an effective barrier for
      preventing exposure to blood-borne pathogens, while others may not.

PMID- 10922265
TI  - Rural surgery.

PMID- 10922266
TI  - Fibrin sealant in the repair of anorectal fistulae.

PMID- 10922267
TI  - Surgical reminiscences: thinking on your feet.

PMID- 10922268
TI  - Horace Green's probang.

PMID- 10922270
TI  - The impact of new diagnostic tests on the management of children with fever.

PMID- 10922269
TI  - Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase
      resetting and suppression.
AB  - Ocular exposure to early morning room light can significantly advance the timing
      of the human circadian pacemaker. The resetting response to such light has a non
      linear relationship to illuminance. The dose-response relationship of the human
      circadian pacemaker to late evening light of dim to moderate intensity has not
      been well established. Twenty-three healthy young male and female volunteers took
      part in a 9 day protocol in which a single experimental light exposure6.5 h in
      duration was given in the early biological night. The effects of the light
      exposure on the endogenous circadian phase of the melatonin rhythm and the acute
      effects of the light exposure on plasma melatonin concentration were calculated.
      We demonstrate that humans are highly responsive to the phase-delaying effects of
      light during the early biological night and that both the phase resetting
      response to light and the acute suppressive effects of light on plasma melatonin
      follow a logistic dose-response curve, as do many circadian responses to light in
      mammals. Contrary to expectations, we found that half of the maximal phase
      delaying response achieved in response to a single episode of evening bright
      light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this
      light (dim room light of approximately 100 lx). The same held true for the acute
      suppressive effects of light on plasma melatonin concentrations. This indicates
      that even small changes in ordinary light exposure during the late evening hours
      can significantly affect both plasma melatonin concentrations and the entrained
      phase of the human circadian pacemaker.

PMID- 10922271
TI  - The cost-effectiveness of adolescent hepatitis A vaccination in states with the
      highest disease rates.
AB  - BACKGROUND: The Advisory Committee on Immunization Practices has recommended
      routine childhood hepatitis A vaccination in states and communities where the
      incidence of disease exceeds the national average, but most adolescents are
      currently unprotected from infection. OBJECTIVE: To estimate clinical and
      economic consequences of vaccinating adolescents against hepatitis A in the 10
      states with the highest disease rates. DESIGN: Decision analysis was used to
      assess cost-effectiveness from societal and health system perspectives. Parameter
      estimates were obtained from national surveillance data, a study of hepatitis A
      cases, and an expert panel. MAIN OUTCOME MEASURES: Reduction in disease
      incidence; costs of vaccination, treatment, and work loss; years of life saved
      (YOLS); and costs per YOLS. RESULTS: In states with the highest disease rates,
      vaccination of adolescents against hepatitis A would reduce the lifetime risk of
      symptomatic infection from 3.3% to 0.7% and prevent loss of 2117 years of life.
      Vaccination of a single birth cohort would cost $30.9 million, yet treatment and
      work loss costs would decline $14.2 million and $23.8 million, respectively.
      Hepatitis A vaccination would cost the health system $7902 per YOLS or $13,722
      per discounted YOLS. Results are most sensitive to variation in the discount rate
      and assumptions regarding long-term vaccine protective efficacy. CONCLUSIONS:
      Hepatitis A vaccination of adolescents in states with high disease rates would
      reduce costs to society. Although health system costs would increase, cost
      effectiveness is comparable to other recommended vaccines and superior to many
      commonly used medical interventions. Arch Pediatr Adolesc Med. 2000;154:763-770

PMID- 10922272
TI  - Prescribing books for immigrant children: a pilot study to promote emergent
      literacy among the children of Hispanic immigrants.
AB  - OBJECTIVES: To assess book-sharing activities within first-generation Hispanic
      immigrant families, and to assess the effect of pediatricians giving books to
      their patients. DESIGN: Survey. PARTICIPANTS: Convenience sample of 122
      predominantly Hispanic immigrant parents of children aged 2 months to 5 years. Of
      these parents, 56 had received children's books from the pediatrician, and 66 had
      not. SETTING: House staff continuity clinic at a university children's hospital.
      MAIN OUTCOME MEASURE: Frequent Book Sharing (FBS) was defined as a parent's
      reporting more than 3 days per week of sharing books with the child. Main
      independent variables included the following: (1) exposure to the Reach Out and
      Read program, defined as having received a children's book from the pediatrician;
      (2) socioeconomics, as measured by parents' years of education and Medicaid
      enrollment; (3) acculturation, as defined by 4 questions relating to parents'
      proficiency with the English language; (4) parent's country of origin; (5) parent
      literacy, as measured by a parent's reporting more than 3 days per week of
      reading alone; (6) parent's age; (7) marital status; (8) household size; (9)
      child's age; (10) child's sex. RESULTS: Ninety percent of the parents were born
      outside of the United States (71% in Mexico), 85% spoke Spanish in the home, and
      63% had completed less than a high-school education. Seventy-five percent of
      children's medical insurance was provided by Medi-Cal (Medicaid), and 9% of
      children were uninsured. Sixty-seven percent spoke exclusively Spanish at home,
      and 84% of parents want their children to learn to read in both English and
      Spanish. High FBS was reported among parents whose children had received books
      from the physician when compared with parents whose children had received no
      books. The odds ratio (OR) was 3.62 (95% confidence interval [CI], 1.40-9.37;
      P<.05). Also associated with FBS were parents reading frequently to themselves
      (OR = 9.52; 95% CI, 2.09-43.27; P<.05) and national origin outside Mexico (OR =
      5.54; 95% CI, 1.59-19.27; P<.05). These findings were independent of parent's
      educational level, parent's employment, parent's age, acculturation, and family
      size. CONCLUSIONS: Pediatricians can promote literacy development among Hispanic
      immigrant children through the provision of free books at well-child visits. Our
      findings also suggest the independent effects of adult literacy and child age.
      Further research is needed to understand the effect of pediatric literacy
      programs on Hispanic immigrant children, their bilingual environments, and their
      readiness for school entry. Arch Pediatr Adolesc Med. 2000;154:771-777

PMID- 10922273
TI  - Very low birth weight and growth into adolescence.
AB  - OBJECTIVE: To compare the growth and pubertal development of very low-birth
      weight (VLBW) children (birth weight <1500 g) and normal-birth-weight (NBW)
      children (birth weight >2499 g) to adolescence to determine if, and at what age,
      VLBW children "catch up." DESIGN: Inception cohort study to age 14 years.
      SETTING: Royal Women's Hospital, Melbourne, Australia. PATIENTS: Eighty-six
      consecutive survivors with a birth weight less than 1000 g, 120 consecutive
      survivors with a birth weight of 1000 to 1499 g, and 60 randomly selected NBW
      controls. Children with cerebral palsy at age 14 years were excluded. MAIN
      OUTCOME MEASURES: Weight, height, and head circumference measurements at birth
      and ages 2, 5, 8, and 14 years converted to z (SD) scores. RESULTS: At age 14
      years, pubertal development was similar in NBW and VLBW children. At ages 2, 5,
      8, and 14 years, VLBW children were significantly shorter and lighter and had
      smaller head circumferences than NBW children. The differences in height and
      weight between VLBW and NBW children were less apparent as SD scores improved in
      VLBW children over time. Within the VLBW group, compared with children with a
      birth weight of 1000 to 1499 g, those with a birth weight less than 1000 g had
      significantly lower weight z scores earlier in childhood but not at age 14 years,
      significantly lower height z scores only at age 2 years, and significantly lower
      head circumference z scores throughout childhood. CONCLUSION: This group of VLBW
      children experienced late catch-up growth to age 14 years but remain smaller than
      their NBW peers. Arch Pediatr Adolesc Med. 2000;154:778-784

PMID- 10922274
TI  - The relationship between children's threats of violence and violent behaviors.
AB  - BACKGROUND: We sought to examine the relationship between students' threats of
      interpersonal violence and self-reported violent behaviors. METHODS: Anonymous
      self-report questionnaires were administered to students in grades 3 through 12
      in schools located in Colorado, Arizona, and Ohio. A survey of 9487 students from
      33 public schools was performed. Ages ranged from 7 to 19 years. Across the 3
      samples, the percentage of African Americans ranged from 6% to 35%, whites from
      31% to 57%, and Hispanics from 5% to 51%. RESULTS: Multivariate logistic
      regression analyses revealed that threatening others infrequently or frequently
      (compared with not threatening others) was significantly associated with violent
      behaviors. Students who infrequently threatened were about 3 to 4 times more
      likely to report exhibiting each of the violent behaviors than students who did
      not threaten others (odds ratio [OR] = 4.08-5.86). The relationship between
      frequently threatening others and violent behaviors was especially strong (OR =
      7.19-24.30) and highest for the most severe forms of violence, knife attacks (OR
      = 15.39-24.30) and shootings (OR = 18.42). CONCLUSIONS: Findings suggest that
      students' threats of harm toward others should be taken seriously, and that
      policies and procedures should be developed to ensure that children who threaten
      others receive proper assessment and management. Arch Pediatr Adolesc Med.
      2000;154:785-790

PMID- 10922275
TI  - "Narrowing the Gap": decreasing emergency department use by children enrolled in
      the Medicaid program by improving access to primary care.
AB  - OBJECTIVE: To evaluate the effectiveness of increased primary care access created
      by North Carolina's Medicaid managed care plan, Carolina Access (CA), in reducing
      unnecessary emergency department (ED) use in Guilford County. METHODS: Emergency
      department records of pediatric visits before and after the implementation of CA
      were analyzed. Variables included patient age, International Classification of
      Diseases, Ninth Revision discharge diagnosis, insurance status, date of visit,
      time of visit, and ZIP code. Visits were classified as either urgent or nonurgent
      based on discharge diagnosis. Rates of ED use per 1000 persons were calculated
      using county population and Medicaid enrollment figures. RESULTS: A total of
      54,742 ED visits occurred between January 1, 1995, and December 31, 1997. Thirty
      eight percent of these visits were by children (defined as those aged 0-18 years
      in this study) enrolled in the Medicaid program. After the implementation of CA,
      monthly ED rates per 1000 children with Medicaid insurance decreased 24% from
      33.5 +/- 5.3 to 25.6 +/- 2.3 (P<.001), which translates to 158 fewer visits per
      month by children enrolled in the Medicaid program. Nonurgent visits among the
      population enrolled in the Medicaid program decreased from an average monthly
      rate per 1000 of 17.9 +/- 3.5 to 11.2 +/- 2.5 after the implementation of CA
      (P<.001), accounting for most of the decrease in total visits. (All data are
      given as mean +/- SD.) The rates of total and nonurgent visits among the
      population not enrolled in the Medicaid program increased slightly. CONCLUSIONS:
      For children with Medicaid insurance, we found a strong temporal relation between
      decreased visits to the ED and increased access to primary care services,
      services that were made available by the implementation of North Carolina's
      Medicaid managed care plan, CA. Specific services that may be responsible for the
      decreased ED use include the expanded availability of primary care physicians and
      the use of telephone triage systems. No similar decrease in ED use was seen among
      the non-Medicaid-insured group. Arch Pediatr Adolesc Med. 2000;154:791-795

PMID- 10922276
TI  - Economic evaluation of use of diphtheria, tetanus, and acellular pertussis
      vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United
      States, 1997.
AB  - OBJECTIVE: To compare the economic costs and benefits associated with using
      either diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) or
      diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) in the
      United States in 1997. DESIGN: Standard cost-benefit analysis, from both the
      societal and health care system perspectives, was performed for each combination
      vaccine as well as for the pertussis components singly. SETTING: A simulated
      cohort of 4.1 million children from birth to age 15 years. MAIN OUTCOME MEASURES:
      Net costs (savings) and benefit-cost ratios (BCRs) RESULTS: Without a vaccination
      program, diphtheria, tetanus, and pertussis disease caused more than 3 million
      cases and more than 28,000 deaths, at a cost of $23.6 billion. From the societal
      perspective, net savings because of the use of DTaP and DTwP were $22.510 million
      and $22.623 million, respectively. The net savings from the acellular pertussis
      component and the whole-cell pertussis component only were $4.362 million and
      $4.474 million, respectively. Benefit-cost ratios for DTaP from a societal and
      health care system perspective were 27:1 and 9:1, respectively. Sensitivity
      analyses of key variables did not result in appreciable changes in results.
      CONCLUSIONS: Compared with no program, vaccination with DTaP or DTwP resulted in
      substantial savings, regardless of the perspective taken and for all sensitivity
      analyses conducted. Compared with DTwP, use of DTaP generated a small cost
      increase that might be offset by the value of other factors, such as increased
      confidence in pertussis vaccination resulting from reduced adverse events. Arch
      Pediatr Adolesc Med. 2000;154:797-803

PMID- 10922277
TI  - Kawasaki syndrome hospitalizations among children in Hawaii and Connecticut.
AB  - OBJECTIVES: To estimate the incidence and describe recent trends of Kawasaki
      syndrome (KS) in 2 different areas of the United States. METHODS: Retrospective
      analysis of Hawaii and Connecticut State KS hospital discharge records for
      children younger than 5 years. RESULTS: In Hawaii, 175 KS hospitalizations for
      children younger than 5 years were reported during 1994 through 1997; the annual
      hospitalization rate per 100,000 children was 47.7. The rate for Hawaiian
      children younger than 1 year (83.2) was greater than that for 1- to 4-year-old
      children (39.0), and most hospitalizations occurred prior to age 2 years (median
      age, 17 months). In Connecticut, 171 KS hospitalizations for children younger
      than 5 years were reported during 1993 through 1996; the annual hospitalization
      rate per 100,000 children was 18.8, and the median age at hospitalization was 28
      months. For both states, most hospitalizations were for boys. Although no clear
      seasonality was apparent, monthly peaks occurred in some of the years from
      December through March. CONCLUSIONS: Kawasaki syndrome seems to remain an endemic
      disease in the United States. A high KS annual hospitalization rate was seen in
      Hawaii, especially in children younger than 1 year, whereas in Connecticut, the
      KS rate was more consistent with those previously reported in the continental
      United States. Arch Pediatr Adolesc Med. 2000;154:804-808

PMID- 10922278
TI  - Maternal expectations, mother-child connectedness, and adolescent sexual debut.
AB  - BACKGROUND: This study examined 3 hypotheses: (1) adolescents who perceive
      maternal disapproval of sexual activity will initiate sexual intercourse later
      than other adolescents; (2) adolescents who feel highly connected to their
      mothers will initiate sexual intercourse later than others; and (3) adolescents
      who perceive maternal disapproval of sexual intercourse are more likely than
      others to experience high levels of connectedness to their mothers, and to have
      mothers who state strong disapproval and talk more frequently with them about
      sex. DESIGN/SETTING: The National Longitudinal Study of Adolescent Health (Add
      Health), a longitudinal study of US students in grades 7 through 12. The Add
      Health core in-home sample consisted of 12,105 students who completed in-school
      and in-home surveys at wave 1). Members of this sample completed a second in-home
      survey 9 to 18 months later at wave 2. PARTICIPANTS: Wave 1 and wave 2 in-home
      surveys were completed by 3322 core sample members who had reported being virgins
      at wave 1, and had resident mothers who completed wave 1 surveys. MAIN OUTCOME
      MEASURES: Time to first sexual intercourse, adolescents' wave 2 reports of
      month/year of first sexual intercourse. RESULTS: Adolescents' perceptions of
      maternal disapproval and high levels of mother-child connectedness were directly
      and independently associated with delays in first sexual intercourse. Adolescents
      were most likely to perceive maternal disapproval if their mothers reported
      strong disapproval and if they reported being highly connected to their mothers.
      CONCLUSION: Perceived maternal disapproval of sexual intercourse, along with
      mother-child relationships characterized by high levels of warmth and closeness,
      may be important protective factors related to delay in adolescents' first sexual
      intercourse. Arch Pediatr Adolesc Med. 2000;154:809-816

PMID- 10922280
TI  - Surveillance protocol for the detection of intracranial abnormalities in
      premature neonates.
AB  - OBJECTIVE: To determine the optimal timing of cranial ultrasound scans (USs) for
      identifying preterm neonates weighing less than 1500 g at birth who develop
      intracranial complications of prematurity. DESIGN/SETTING: Observational study at
      an urban county hospital. METHODS: Serial USs from neonates with less than 1500-g
      birth weight (BW) admitted to the neonatal intensive care unit between January
      1995 and December 1996 were reviewed by a pediatric neuroradiologist in a blinded
      random manner. RESULTS: Two hundred forty-eight neonates (78%) underwent at least
      3 USs, 32 (10%) had 2 USs and 37 (12%) only 1 US. The initial US was normal in
      156 neonates (49%) and abnormal in 161 (57%). The principal abnormalities
      included intraventricular hemorrhage (IVH) (n = 74), periventricular echogenicity
      (PVE) (n = 68), ventriculomegaly (n = 7), and solitary cysts (n = 9). Severe IVH
      (n = 17) occurred in 13 (11.4%) of 114 neonates at less than 1000-g BW and 4 (5%)
      of 79 neonates of BW 1000 to 1250 g. In 11 cases (65%), the severe IVH was
      clinically unsuspected. For neonates weighing less than 1000 g, IVH was diagnosed
      by days 3 to 5 in 10 (77%) of 13, by days 10 to 14 in 11 (84%) of 13, and by day
      28 in all neonates; for neonates 1001 to 1250 g, IVH was diagnosed in 1 (24%) of
      4 by days 3 to 5, 2 (50%) of 4 by days 10 to 14, and 3 (75%) of 4 by day 28. One
      infant's condition was diagnosed on routine US before discharge from the
      hospital. Cystic periventricular leukomalacia (PVL) was noted in 9 neonates; in 4
      of the 9 cases, increased PVE was present on the initial US and cyst formation
      was obvious by the second US. For 4 neonates (3 with BW <1000 g), all routine USs
      were negative and cystic PVL was noted on the predischarge US in these cases.
      Nonobstructive ventriculomegaly in the absence of IVH or cystic PVL was observed
      in 14 neonates. In 6, it was noted on the initial screening US; in 4 of the
      cases, it evolved after the third screening US. Two hundred fifty-six neonates
      had a US before discharge from the hospital; 181 (72%) were normal and 75 (28%)
      abnormal. Nine significant lesions were identified by the US before discharge
      from the hospital (ie, severe IVH [n = 1], cystic PVL [n = 4], and
      ventriculomegaly [n = 4]). CONCLUSIONS: The following screening protocol is
      recommended: (1) Neonates of less than 1000-g BW: initial US on days 3 to 5
      (should identify at least 75% of cases of IVH and some PVE abnormalities); second
      US on days 10 to 14 (should detect at least 84% of IVH and identify early
      hydrocephalus and early cyst formation); third scan on day 28 (should detect all
      cases of IVH, as well as assess PVE and ventricular size); and final scan before
      discharge from the hospital (should detect approximately 20% of significant late
      onset lesions). (2) Neonates of 1000- to 1250-g BW: initial US at days 3 to 5
      (should detect at least 40% of significant abnormalities); a second scan at day
      28 (should detect at least 70% of significant abnormalities); and a predischarge
      scan (should detect all late-onset significant lesions). (3) Neonates of 1251- to
      1500-g BW: an initial scan at days 3 to 5; and a second scan before discharge
      from the hospital if the clinical course is complicated. Arch Pediatr Adolesc
      Med. 2000;154:822-826

PMID- 10922279
TI  - Cost analysis of enteroviral polymerase chain reaction in infants with fever and
      cerebrospinal fluid pleocytosis.
AB  - BACKGROUND: Infants with fever and cerebrospinal fluid (CSF) pleocytosis are
      routinely admitted to the hospital for parenteral antibiotic therapy for
      potential bacterial meningitis pending results of CSF culture. Published
      estimates suggest that 90% of all episodes of meningitis are caused by
      enterovirus. Enteroviral polymerase chain reaction (ePCR) has a sensitivity of
      92% to 100% and a specificity of 97% to 100% in CSF. OBJECTIVE: To compare a
      management strategy using ePCR with current practice to determine potential
      savings by allowing earlier discharge. METHODS: Decision analysis comparing 2
      strategies for the care of a retrospective cohort of infants with fever and CSF
      pleocytosis: standard practice vs ePCR testing of all CSF samples. Model
      assumptions include the following: (1) standard practice patients continue
      parenteral antibiotic therapy until CSF cultures are negative at 48 hours, (2)
      patients with positive ePCR results would be discharged after 24 hours, (3)
      patients with positive ePCR results have a negative CSF culture, and (4) costs
      are calculated from actual patient charges with a cost-to-charge ratio of 0.65.
      SUBJECTS: All infants aged 28 days to 12 months admitted to an urban teaching
      hospital with fever, CSF pleocytosis, and a negative CSF Gram stain from January
      1996 through December 1997. OUTCOME MEASURE: Total cost of hospitalization.
      RESULTS: A total of 126 infants were identified. One hundred twelve (89%) were
      discharged with a diagnosis of aseptic meningitis; 72% of these cases occurred
      during the peak enterovirus season (June to October). Three of 3 patients with
      positive CSF cultures had bacterial growth within 24 hours of admission. Mean
      length of stay for patients with aseptic meningitis was 2.3 days (SD, +/-1.4
      days). Total cost of hospital care for all 126 infants was $381,145. In our
      patient population, total patient costs would be reduced by the ePCR strategy if
      enterovirus accounts for more than 5. 9% of all meningitis cases. Varying the
      sensitivity of the ePCR assay from 100% to 90% changes the "break-even"
      prevalence from 5.8% to 6.5%. Total cost savings of 10%, 20%, and 30% would occur
      at an enteroviral meningitis prevalence of 36.3%, 66.7%, and 97.1%, respectively.
      CONCLUSIONS: Enteroviral PCR analysis of CSF for infants admitted to the hospital
      with meningitis can result in cost savings when the prevalence of enteroviral
      meningitis exceeds 5.9%. Limiting use of ePCR to the enterovirus season would
      increase cost savings. A prospective study is needed to validate these results.
      Arch Pediatr Adolesc Med. 2000;154:817-821

PMID- 10922281
TI  - Cerebrospinal fluid protein concentration in pediatric patients: defining
      clinically relevant reference values.
AB  - OBJECTIVES: To define clinically relevant reference ("normal") values for
      cerebrospinal fluid (CSF) protein concentrations in pediatric patients who were
      evaluated for meningitis by traditional criteria and by enterovirus-polymerase
      chain reaction (EV-PCR). DESIGN AND PATIENTS: A cohort of 906 consecutive
      pediatric patients to receive CSF analysis at St Louis Children's Hospital, St
      Louis, Mo, from June 1, 1998, to December 31,1998, was studied for clinical and
      laboratory data. Age-dependent CSF protein concentrations were then derived from
      a reference group of 225 patients in whom meningitis and other neurologic
      diseases were excluded by traditional clinical or laboratory criteria (excluding
      EV-PCR). Available CSF samples from 132 patients of the reference group were
      subsequently tested for EV-PCR. RESULTS: In the reference group, the CSF protein
      concentration was highest and most variable in neonates, with a maximum of
      approximately 1.0 g/L. Cerebrospinal fluid protein concentration decreased
      rapidly to a nadir by 6 months and remained low throughout childhood, rarely
      exceeding 0.3 g/L and, finally, increasing in adolescence toward adult values.
      Enterovirus- polymerase chain reaction was positive in CSF of 11% of the
      reference group, with EV-PCR-positive patients having significantly higher CSF
      protein concentrations than EV-PCR-negative patients aged between 4 months and 14
      years. CONCLUSIONS: Reference values for CSF protein exhibit a characteristic age
      dependence in pediatric patients. Continued standard use of adult reference
      values in the pediatric population is inappropriate. The unexpected finding of a
      positive EV-PCR in patients not diagnosed with meningitis by traditional criteria
      further emphasizes the importance of selecting the most clinically relevant
      reference group for age and other variables when defining normal laboratory
      values. Arch Pediatr Adolesc Med. 2000;154:827-831

PMID- 10922282
TI  - The status of immunization measurement and feedback in the United States.
AB  - BACKGROUND: A large body of scientific and programmatic data has demonstrated
      that provider measurement and feedback raises immunization coverage. Starting in
      1995, Congress required that all states measure childhood immunization coverage
      in all public clinics, and federal grant guidelines encourage private practice
      measurements. OBJECTIVES: To determine state immunization measurement rates and
      examine risk factors for high rates. METHODS: Review of 1997 state reports, with
      correlation of measurement rates to birth cohort and provider numbers,
      public/private proportions, and vaccine distribution systems. RESULTS: Of the
      9505 public clinics, 48% were measured; 4 states measured all clinics; 29
      measured a majority. Measurement rates were highest for Health Department clinics
      (67%), lower for community/migrant health centers (39%), and lowest for other
      clinics (22%). Rates were highly correlated among categories of clinics
      (r>+0.308, P<.03), and the fewer the clinics, the higher the measurement rates (r
      = -0.351, P =. 01), but other factors were not significant. Of the 41,378 private
      practices, 6% were measured; no state measured all its practices; 1 measured a
      majority. Private practice measurement rates were not correlated to public clinic
      measurement rates or other factors examined. Of the 50,883 total providers, 14%
      were measured; no state measured all providers; 2 measured a majority. A trend
      toward higher measurement rates was found in states with fewer providers (r = -0.
      266, P =.06). CONCLUSIONS: Three years after the congressional mandate, only a
      minority of public clinics and very few private practices had their immunization
      coverage measured. Greater efforts will be needed to assure implementation of the
      intervention. Arch Pediatr Adolesc Med. 2000;154:832-836

PMID- 10922283
TI  - Adolescent obesity in a low-income Mexican American district in South Texas.
AB  - BACKGROUND: The Third National Health and Nutrition Examination Survey, 1988
      1994(NHANES III) revealed that 11.5% of adolescents were obese. The NHANES III
      sample size for Mexican Americans was small. OBJECTIVE: To determine the
      prevalence of adolescent obesity in a South Texas population that is
      preponderantly low-income Mexican Americans. DESIGN: Cross-sectional prevalence
      study. SETTING: All secondary school campuses of one rural independent school
      district with a low-income Mexican American population. SUBJECTS: Four thousand
      three hundred seventy-five students, aged between 12 and 17 years, enrolled in 4
      secondary school campuses of 1 Rio Grande Valley, South Texas, independent school
      district for academic year 1998-1999. MAIN OUTCOME MEASURES: Body mass index
      (BMI) was calculated for all 4375 students using weights and heights measured by
      school nurses on enrollment. Each student's BMI was then plotted on a sex
      specific chart and the percentile range for age was determined. Those within the
      85th to the 95th percentile were classified as at risk for obesity and those
      above the 95th percentile were classified as obese. RESULTS: Of 2149 adolscent
      girls and 2226 adolescent boys, 18% were at risk for obesity and 22. 1% were
      obese. A total of 40.1% had a BMI at the 85th percentile or higher for age and
      sex. The prevalence of obesity also continues to rise even after puberty more
      markedly in adolescent girls than adolescent boys. Furthermore, the mean BMI
      progressively increases with age and is generally at the 85th percentile or
      higher. CONCLUSIONS: Our data revealed a much higher prevalence rate of obesity
      in this adolescent Mexican American population than the rate obtained in NHANES
      III. It is even higher than the rate specific for Mexican American adolescents in
      NHANES III. The NHANES III significantly underestimates the prevalence of
      adolescent obesity in preponderantly impoverished Mexican American adolescents.
      This consequently leads to underestimation of the public health risks as well as
      the present and future cost of health care associated with obesity in this
      population. Arch Pediatr Adolesc Med. 2000;154:837-840

PMID- 10922284
TI  - Radiological case of the month. Coarctation of the aorta in Hurler syndrome.

PMID- 10922285
TI  - Picture of the month. Lingual thyroid.

PMID- 10922286
TI  - Pathological case of the month. Primary bullous emphysema with spontaneous
      pneumothorax.

PMID- 10922287
TI  - Human monocytic ehrlichiosis: a potentially severe disease in children.

PMID- 10922288
TI  - Early newborn hospital discharge after delivery: a comment on cost-effectiveness.

PMID- 10922289
TI  - Pediatric forum: early newborn hospital discharge after delivery: A comment on
      cost-effectiveness

PMID- 10922290
TI  - Recurrent pneumonia in children.

PMID- 10922292
TI  - Pediatric forum: genetic testing of adolescents: is It in their best interest?

PMID- 10922291
TI  - Genetic testing of adolescents: is it in their best interest?

PMID- 10922293
TI  - Renal handling of magnesium in fish: from whole animal to brush border membrane
      vesicles.
AB  - Of all known vertebrate tissues, the kidneys of fish are the champions of Mg
      transport. They can switch from Mg conservation in fresh water to Mg wasting in
      seawater. High rates of tubular transport and the ability to alternate between Mg
      reabsorption and secretion make fish kidneys the model of choice investigating
      the mechanisms of transepithelial and membrane Mg transport and its regulation by
      extracellular hormones and intracellular messengers. Studies in isolated proximal
      tubules indicate active transepithelial Mg transport that requires metabolic
      energy for both tubular reabsorption and secretion. Whether active transport is
      primary and mediated by a Mg-pump, or secondary and mediated via cotransport or
      antiport, is unknown. In fresh water fish, the active transport pathway appears
      to include a Mg-channel located in brush-border membranes of proximal tubules.
      Although plasma Mg concentrations are well protected, a primary hormone
      controlling Mg balance has yet to be identified in any animal. Moreover, the
      mechanisms of intracellular Mg homeostasis, especially in epithelial cells with
      high Mg throughput, are unknown. New methods, including Mg imaging and
      genetic/molecular approaches promise to unravel Mg transport mechanisms in
      teleost renal tubules.

PMID- 10922294
TI  - Role and regulation of apoptotic cell death in the kidney. Y2K update.
AB  - Apoptosis is an active form of cell death that, in balance with mitosis,
      regulates cell number. Cell number abnormalities are a frequent feature of renal
      disease. We now review current concepts on the molecular regulation of apoptotic
      cell death, including the influence of survival and lethal factors from the
      extracellular microenvironment as well as the role of intracellular regulators of
      apoptosis, such as death receptors, proapoptotic and antiapoptotic bcl2-related
      proteins, the mitochondria and caspases. In addition the role of apoptosis in the
      genesis, persistence and progression and remodeling and resolution of renal
      injury is discussed. Information on the expression and function of apoptosis
      regulatory proteins in specific renal syndromes is summarized. Finally, future
      perspectives in research and clinical intervention are discussed.

PMID- 10922295
TI  - Epithelial magnesium transport and regulation by the kidney.
AB  - Magnesium is the fourth most abundant cation in the body and the second most
      common cation in the intracellular fluid. It is the kidney that provides the most
      sensitive control for magnesium balance. About a 80% of the total serum magnesium
      is ultrafilterable through the glomerular membrane. In all of the mammalian
      species studied to date, the proximal tubule of the adult animal reabsorbs only a
      small fraction, 10-15%, of the filtered magnesium. Unlike the adult proximal
      convoluted tubule that of young rats (aged 13-15 days) reabsorbs 50-60% of
      filtered magnesium along the proximal tubule together with sodium, calcium, and
      water. Micropuncture experiments, in every species studied to date, indicates
      that a large part (approximately 60%) of the filtered magnesium is reabsorbed in
      the loop of Henle. Magnesium reabsorption in the loop occurs within the cortical
      thick ascending limb (cTAL) by passive means driven by the transepithelial
      voltage through the paracellular pathway. Micropuncture experiments have clearly
      showed that the superficial distal tubule reabsorbs significant amounts of
      magnesium. Unlike the thick ascending limb of the loop of Henle, magnesium
      reabsorption in the distal tubule is transcellular and active in nature. Many
      hormones and nonhormonal factors influence renal magnesium reabsorption to
      variable extent in the cTAL and distal tubule. Moreover, nonhormonal factors may
      have important implications on hormonal controls of renal magnesium conservation.
      Dietary magnesium restriction leads to renal magnesium conservation with
      diminished urinary magnesium excretion. Adaptation of magnesium transport with
      dietary magnesium restriction occurs in both the cTAL and distal tubule.
      Elevation of plasma magnesium or calcium concentration inhibits magnesium and
      calcium reabsorption leading to hypermagnesiuria and hypercalciuria. The
      identification of an extracellular Ca2+/Mg2+ -sensing receptor located on the
      peritubular side of cTAL and distal tubule cells explains this phenomenon. Loop
      diuretics, such as furosemide and bumetanide, diminish salt absorption in the
      cTAL whereas the distally acting diuretics, amiloride and chlorothiazide
      stimulate magnesium reabsorption within the distal convoluted tubule. Finally,
      metabolic acidosis, potassium depletion or phosphate restriction can diminish
      magnesium reabsorption within the loop and distal tubule. Research in the 90's
      have greatly contributed to our understanding of renal magnesium handling.

PMID- 10922296
TI  - Regulation of cellular magnesium.
AB  - The abundance of magnesium (Mg2+) within mammalian cells is consistent with its
      relevant role in regulating tissue and cell functions. At the last count, more
      than three hundred and fifty enzymes, aside from metabolic cycles, appear to
      require and be regulated by concentrations of Mg2+ that are well within the
      physiological range observed in tissues and cells. The absence of detectable
      major changes in cellular free [Mg2+], and the extremely slow turn-over of the
      cation across the cell plasma membrane under quiescent condition has supported
      for more than three decades the assumption that cellular Mg2+ content is kept
      constant at the level necessary for enzyme and channel function, and that its
      concentration does not require drastic and rapid changes to form complex with ATP
      and other phosphonucleotides. In the last decade, a large body of new
      experimental observations has significantly reverted this way of thinking.
      Compelling evidence now suggests that large fluxes of Mg2+ can cross the cell
      plasma membrane in either direction following a variety of hormonal and non
      hormonal stimuli, resulting in major changes in total and, to a lesser extent,
      free Mg2+ content within tissues, and in a marked variation in the opposite
      direction of circulating Mg2+ level. The present review will attempt to update
      our knowledge in this area and provide some insights on how changes in cellular
      Mg2+ content can result in a modification of the activity rate for several
      cellular enzymes.

PMID- 10922297
TI  - Magnesium transport in the gastrointestinal tract.
AB  - Magnesium is an essential (macro) mineral in vertebrates with many biochemical
      and physiological functions including activation of enzymes, involvement into
      metabolic pathways, regulation of membrane channels and muscle contraction.
      Despite these important functions, Mg++ homeostasis is not regulated by hormones,
      but depends on absorption from the gastrointestinal tract, requirement of the
      body, and excretion via the kidneys. The present review summarizes data on
      epithelial Mg++ transport in the gut via paracellular and cellular pathways.
      Paracellular movement of Mg++ is only important in leaky epithelia as in the
      small intestine. The transcellular transport of Mg++, luminal uptake and
      basolateral extrusion, require membrane proteins which increase the low
      permeability of the membranes and facilitate the movement of Mg++ through these
      lipid bilayers. Proposals have been made how these proteins could mediate Mg++
      transport. There is now a growing body of evidence for a PD-dependent luminal
      Mg++ uptake via a carrier or channel. Furthermore, PD-independent uptake
      mechanisms have been demonstrated which may be represented by Mg++/2cation+
      exchange or co-transport of Mg++ with anions. The mechanism of a basolateral
      extrusion is not clear. A Na+/Mg++ exchange, well characterized in non-polar
      cells, has been suggested which leads to the proposal that there is a secondary
      active transport system for Mg++. It can readily be learned from this fragmentary
      knowledge of transepithelial Mg++ transport that future research must be directed
      to a study of the relevant membrane proteins (carriers or channel for Mg++) in
      order to close the gap between the incompletely described epithelial Mg++
      transport mechanisms and the well established transport systems, e.g. , sodium or
      glucose.

PMID- 10922298
TI  - Specificity in the cAMP/PKA signaling pathway. Differential
      expression,regulation, and subcellular localization of subunits of PKA.
AB  - A large number of hormones, neurotransmitters and other signal substances utilize
      adenosine 3',5' cyclic monophosphate (cAMP) as an intracellular second messenger.
      Cyclic AMP 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 cAMP-dependent protein kinase (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 will describe features of this
      signaling pathway that may contribute to explain how differential effects of cAMP
      may be contributed to features of the PKA signaling pathway.

PMID- 10922299
TI  - Regulation of intracellular free magnesium in central nervous system injury.
AB  - Traumatic injury to the central nervous system (CNS) initiates an autodestructive
      cascade of biochemical and pathophysiological changes that ultimately results in
      irreversible tissue damage. Known as secondary injury, this delayed injury
      process is multifactorial in nature and it is generally thought that the
      simultaneous attenuation of a number of the secondary injury factors will be
      required for interventional therapies to have a significant beneficial effect on
      outcome. This review summarizes the growing body of evidence that suggests that
      magnesium plays a pivotal role in the secondary injury process following CNS
      trauma, affecting a number of secondary injury factors including neurotransmitter
      release and activity, ion changes, oxidative stress, protein synthesis, and
      energy metabolism. By having effects on such a range of secondary injury factors
      following trauma, pharmacological studies have shown that magnesium may be an
      effective therapy following neurotrauma, improving survival, motor outcome and
      alleviating cognitive deficits.

PMID- 10922300
TI  - Natural history of idiopathic IgA nephropathy: role of clinical and histological
      prognostic factors.
AB  - Idiopathic immunoglobulin A nephropathy is characterized by an extreme
      variability in clinical course and sometimes by the unpredictability of the
      ultimate outcome. Among the numerous studies published in the last 15 years that
      have calculated the actuarial renal survival and tried to individuate the
      prognostic role of the clinical and histological features present at the onset of
      the disease or the time of biopsy, we chose to analyze critically the results of
      the most valid (30 studies). Actuarial renal survival at 10 years in adults was
      between 80% and 85% in most of the European and Asian studies, but it was less in
      studies from the United States and exceeded 90% in the few studies of children.
      Concordance existed in this selected literature that impairment of renal
      function, severe proteinuria, and arterial hypertension are the strongest and
      more reliable clinical predictors of an unfavorable outcome. However, analysis of
      the prognostic value of morphological lesions was more difficult because they
      have been characterized in some studies using an overall score or histological
      classes of progressively more severe involvement and, in others, using a
      semiquantitative grading of individual glomerular, tubular, interstitial, and
      vascular changes. In adult patients, a high score of glomerular and
      tubulointerstitial lesions, corresponding to classes IV and V of the Lee or Haas
      classifications, predicted a more rapid progression. When single lesions were
      analyzed separately, glomerulosclerosis and interstitial fibrosis appeared to be
      the strongest, most reliable predictors of unfavorable prognosis. More
      controversial was the role of crescents and capsular adhesions. None of the
      immunohistological features was found to be a risk factor for progression in the
      more accurate statistical analyses. The same histological features predicted
      outcome in children, although the severity of lesions at the time of biopsy was
      usually less than that in adults. However, in the single patient, even the
      evaluation of these prognostic markers sometimes fails to correctly predict
      outcome, probably because of the heterogeneity of the disease and the
      discontinuous activity of some injuring mechanisms during its course.

PMID- 10922301
TI  - Polyene antibiotics: relative degrees of in vitro cytotoxicity and potential
      effects on tubule phospholipid and ceramide content.
AB  - Polyene antibiotic administration is limited by dose-dependent nephrotoxicity.
      The latter is believed to be mediated by polyene anchoring to plasma membrane
      cholesterol, resulting in pore formation, abnormal ion/solute flux, adenosine
      triphosphate (ATP) declines, and, ultimately, a loss of tubule viability. The
      relative nephrotoxicity of these agents and their liposomal preparations has
      remained poorly defined. Thus, freshly isolated mouse proximal tubules or
      cultured human proximal tubule (HK-2) cells were exposed to either nystatin,
      amphotericin B, or three different polyene liposomal preparations (Nyotran,
      AmBisome, or Abelcet; 4 to 64 microg/mL). The impact of these agents on (1)
      plasma membrane injury (sodium-driven ATP consumption, assessed by ATP-adenosine
      diphosphate [ADP] ratios); (2) cellular susceptibility to superimposed injury
      (chemical hypoxia or ferrous ammonium sulfate-mediated oxidative stress; assessed
      by lactate dehydrogenase release); and (3) membrane cholesterol, phospholipid,
      and ceramide expression was assessed. Amphotericin B was more cytotoxic than
      nystatin (approximately 25% to 50% greater ATP-ADP ratio declines). Most of this
      toxicity could be eliminated by polyene liposomal formulation. Nevertheless, the
      liposomal polyenes still fully sensitized tubule cells to superimposed chemical
      hypoxic (antimycin/deoxyglucose), but not oxidant, attack. Nystatin and
      amphotericin B caused acute increments in tubule sphingomyelin
      phosphatidylcholine ratios and ceramide content (indicating an impact on the
      plasma membrane extending beyond the classic view of pore formation with ion
      flux). In conclusion, (1) nystatin is seemingly less cytotoxic than amphotericin
      B (in contrast to the prevailing clinical view); (2) liposomal formulation
      markedly decreases this cytotoxicity; (3) despite this reduced toxicity,
      liposomal polyenes are still able to render tubule cells more vulnerable to
      selected forms of superimposed injury; and (4) acute alterations in plasma
      membrane phospholipid and ceramide expression are previously unrecognized
      consequences and potential mediators of polyene-mediated tubular cell attack.

PMID- 10922302
TI  - Use of mycophenolate mofetil in resistant membranous nephropathy.
AB  - Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Optimal
      therapy for this disease is still debated. We report our experience using
      mycophenolate mofetil (MMF), an immunosuppressive agent widely used in transplant
      recipients, to treat 16 nephrotic patients with MN. All patients had biopsy
      documented MN; secondary forms were ruled out. Fifteen patients had steroid
      resistant disease; cytotoxic agents had failed in 6 patients and cyclosporine
      therapy had failed in 5 patients. Patients were treated with MMF (dose range, 500
      to 2,000 mg) for a mean of 8 months. Six patients experienced a halving of
      proteinuria, which occurred after a mean duration of 6 months of therapy. Partial
      remissions occurred in 2 patients. There were no significant changes in mean
      values for serum creatinine, serum albumin, or proteinuria. Mean cholesterol
      levels were significantly less. Side effects of MMF were infrequent and generally
      mild. In summary, MMF appears to reduce proteinuria in some patients with
      idiopathic MN previously resistant to steroids, cytotoxic agents, or
      cyclosporine. Further trials with this agent are warranted.

PMID- 10922303
TI  - Distribution of renal lesions in idiopathic systemic vasculitis: A three
      dimensional analysis of 87 glomeruli.
AB  - Extracapillary proliferation and fibrinoid necrosis are the main diagnostic
      glomerular lesions in renal biopsy specimens of patients with idiopathic systemic
      vasculitis. Neither the incidence nor the correlation between extracapillary
      proliferation and fibrinoid necrosis in renal biopsy specimens from patients with
      systemic vasculitis has been systematically evaluated. By means of a three
      dimensional analysis, we made a topographic reconstruction of the distribution of
      extracapillary proliferation and fibrinoid necrosis in affected glomeruli and
      tested different biopsy-processing protocols to optimize histopathologic analysis
      in clinical practice. Paraffin blocks of renal biopsy specimens from six patients
      diagnosed with systemic vasculitis were completely and serially sectioned in 2
      microm thick sections and stained with the Gomori trichrome method. Glomeruli
      were scored per section for the presence of fibrinoid necrosis and extracapillary
      proliferation. Subsequently, a three-dimensional reconstruction was obtained for
      87 glomeruli. In only one glomerulus did fibrinoid necrosis occur without
      extracapillary proliferation; in 51%, a combination of the two lesions was found;
      in 22%, extracapillary proliferation occurred in the absence of fibrinoid
      necrosis; and 26% did not show either lesion. Using the standard protocol from
      our department (ie, evaluation of 20 consecutive sections in various stainings),
      the chance of finding extracapillary proliferation was 100% and that of finding
      fibrinoid necrosis was 73%. If 5 sections stained with the Gomori trichrome were
      added, the latter percentage increased to 86%. Using skip-serial sections, even
      better results (87% to 92%) were obtained, with four skips as the best option
      (92%). In conclusion, our finding that fibrinoid necrosis rarely occurs in the
      absence of extracapillary proliferation may imply that both lesions are
      etiologically related. In addition, our observations indicate that the incidence
      of fibrinoid necrosis may be underestimated in clinical practice, depending on
      the number of sections evaluated.

PMID- 10922304
TI  - Progress in blood pressure control in autosomal dominant polycystic kidney
      disease.
AB  - Hypertension occurs commonly in autosomal dominant polycystic kidney disease
      (ADPKD) and is an important factor in the progression of the disease and
      cardiovascular mortality. The aim of this prospective 15-year study is to report
      the rate of blood pressure control and the potential effect of a 10-point
      education program developed by our center for ADPKD patients and their
      physicians. The patients' blood pressure treatment was managed by their primary
      care physicians. Three 5-year periods were analyzed in which similar rates of
      hypertension in patients with ADPKD were present (63% to 68%). In the first
      period (1985 to 1989), the rate of blood pressure control (<140/90 mm Hg) was 38%
      for 216 hypertensive patients with ADPKD. From 1990 to 1994, the percentage of
      blood pressure control increased to 55% in 194 hypertensive patients with ADPKD
      (P < 0.001 versus 1985 to 1989); and the level of blood pressure control
      increased to 64% in 181 hypertensive patients with ADPKD during 1995 to 1999 (P <
      0.001 versus 1985 to 1989). Although this percentage of blood pressure control in
      patients with ADPKD remains suboptimal, it compares very favorably with the 27%
      estimated blood pressure control in patients with essential hypertension from
      1991 to 1994 in the United States.

PMID- 10922305
TI  - Diabetes, hemoglobin A(1c), cholesterol, and the risk of moderate chronic renal
      insufficiency in an ambulatory population.
AB  - Moderate chronic renal insufficiency is common, with 12.5 million individuals in
      the United States estimated to have a creatinine clearance less than 50
      mL/min/1.73 m(2). Little is known about the risk factors for moderate chronic
      renal insufficiency. We studied 1, 428 subjects with Cockcroft-Gault-estimated
      creatinine clearances greater than 70 mL/min in a hospital-based ambulatory
      population. Over a mean of 5.7 +/- 1.3 years, 86 subjects developed moderate
      chronic renal insufficiency, defined as a decrease in creatinine clearance to
      less than 60 mL/min (1.1 case/100 person-years). Risk factors for moderate
      chronic renal insufficiency were identified using a proportional hazards model
      controlling for age, sex, race, systolic blood pressure, and angiotensin
      converting enzyme (ACE) inhibitor use. The risk for developing moderate chronic
      renal insufficiency was associated with diabetes mellitus (relative risk, 2.1;
      95% confidence interval [CI], 1.3 to 3.3) and elevated hemoglobin A(1c) levels.
      Compared with subjects with normoglycemia (hemoglobin A(1c) </= 5.7%), the
      relative risk for moderate chronic renal insufficiency for patients in the upper
      quartile of hemoglobin A(1c) (>9.0%) was 2.7 (95% CI, 1.4 to 5.1). The
      development of moderate chronic renal insufficiency was also independently
      predicted by elevated maximum serum cholesterol level. Compared with subjects
      with maximum cholesterol levels of 250 mg/dL or less, the relative risk for those
      with maximum cholesterol levels greater than 350 mg/dL was 2.4 (95% CI, 1.1 to
      5.2). Similar relative risks were obtained when moderate chronic renal
      insufficiency was defined by the development of an increase in serum creatinine
      level. Hypercholesterolemia was also associated with moderate chronic renal
      insufficiency among persons without diabetes. In conclusion, the risk for
      developing moderate chronic renal insufficiency is increased by diabetes and
      elevated hemoglobin A(1c) and serum cholesterol levels. Modification of these
      risk factors may decrease the incidence of moderate chronic renal insufficiency.

PMID- 10922306
TI  - Hematocrit levels and associated Medicare expenditures.
AB  - Clinical studies and the National Kidney Foundation-Dialysis Outcomes Quality
      Initiative guidelines suggest that a target hematocrit of 33% to less than 36% is
      appropriate for patient benefit. Previous studies have shown an association of
      lower risks for death and hospitalization when hematocrits were 33% to less than
      36%. In this study, we assessed the relationship between hematocrit value and
      associated Medicare expenditures, analyzing incident Medicare hemodialysis
      patients from January 1, 1991, through June 30, 1995. All patients survived at
      least 90 days to normalize eligibility and an additional 6-month entry period to
      assess comorbidity and hematocrit values. All patients were followed up from July
      1, 1991, through December 31, 1996. We assessed the association between
      hematocrit values in the 6-month entry period and the Medicare-allowable Part A
      and Part B per-member-per-month (PMPM) expenditures in the follow-up period,
      controlling for other variables, including patient demographic characteristics,
      comorbid conditions, and severity of disease. We found that hematocrits of 33% to
      less than 36% and 36% and higher were associated with lower Medicare-allowable
      payments in the follow-up period. Compared with reference patients with
      hematocrits of 30% to less than 33%, the Medicare-allowable PMPM expenditures
      were significantly greater for patients with hematocrits less than 27% and 27% to
      less than 30% (12. 7% and 5.3%, respectively), and the Medicare-allowable PMPMs
      were significantly less for patients with hematocrits of 33% to less than 36% and
      36% and higher (6.0% and 8.2%, respectively). Although these findings suggest
      that the treatment of anemia may be associated with significant savings in total
      patient Medicare expenditures, caution should be considered because these
      findings are associations and should not be deemed as showing causality.

PMID- 10922307
TI  - Extended daily dialysis: A new approach to renal replacement for acute renal
      failure in the intensive care unit.
AB  - Continuous venovenous hemofiltration (CVVH) is an effective form of renal
      replacement therapy for acute renal failure (ARF) that offers greater hemodynamic
      stability and better volume control than conventional hemodialysis in the
      critically ill, hypotensive patient. However, the application of CVVH in the
      intensive care unit (ICU) has several disadvantages, including intensive nursing
      requirements, continuous anticoagulation, patient immobility, and expense. We
      describe a new approach to the treatment of ARF in the ICU, which we have termed
      extended daily dialysis (EDD). In this study, EDD was compared with CVVH in 42
      patients: 25 patients were treated with EDD for a total of 367 treatment days,
      and 17 patients were treated with CVVH for a total of 113 days. Median treatment
      time per day was 7.5 hours for EDD (range, 6 to 8 hours, 25th to 75th percentile)
      versus 19.5 hours for CVVH (range, 13.4 to 24 hours; P < 0.001). Mean arterial
      blood pressures (MAPs) did not differ significantly for patients treated with EDD
      when measured predialysis (median MAP, 70 versus 67 mm Hg for CVVH; P = 0.078),
      midway through daily treatment (70 versus 68 mm Hg for CVVH; P = 0.083), or at
      the end of treatment (71 versus 69 mm Hg for CVVH; P = 0.07). Net daily
      ultrafiltration was similar for the two treatment modalities (EDD, median, 3,000
      mL/d; range, 1,763 to 4,445 mL/d; CVVH, 3,028 mL/d; range, 1,785 to 4,707 mL/d; P
      = 0.514). Anticoagulation requirements were significantly less for patients
      treated with EDD (median dose of heparin, 4,000 U/d; range, 0 to 5,800 U/d versus
      21,100 U/d; range, 8,825 to 31,275 U/d for patients treated with CVVH; P <
      0.001). We found that EDD eliminated the need for constant supervision of the
      dialysis machine by a subspecialty dialysis nurse, allowing one nurse to manage
      more than one treatment. Overall, EDD was well tolerated by the majority of
      patients, offered many of the same benefits provided by CVVH, and was technically
      easier to perform.

PMID- 10922308
TI  - Causes of end-stage renal failure in black patients starting renal replacement
      therapy.
AB  - In the United States, blacks are more frequently diagnosed than whites with end
      stage renal failure (ESRF) from primary hypertension or diabetic nephropathy. We
      performed a validation retrospective case-note study of all blacks with ESRF who
      started renal replacement therapy (RRT) at three teaching hospitals in London,
      England, during 1991 to 1995 to investigate and validate the causes of primary
      renal disease using standard criteria. We identified 144 black patients with a
      mean age of 52.0 +/- 16.0 (SD) years; 59% were men and 32% had renal histological
      data. One hundred forty-four whites who were matched for age, sex, and onset of
      RRT (42% with renal histological data) underwent a similar validation exercise.
      Before the validation, the principal working diagnosis in the black patients had
      been diabetic nephropathy in 35% (89%, type 2; 11%, type 1); primary
      hypertension, 19%; glomerulonephritis (GN), 18%; and uncertain cause, 15%. After
      validation analysis, this changed to diabetes, 38% (16% biopsy proven);
      uncertain, 24%; GN, 20%; and primary hypertension, only 10% (28% biopsy proven).
      Among the uncertain cases (n = 34), 19 patients had hypertension, but this could
      not be established as the primary disease; 94% of all blacks had hypertension,
      accelerated in 21%. Among whites, only 3.5% had primary hypertension, and this
      proportion was not changed by the validation study. Type 2 diabetes is the most
      common single cause of ESRF in black patients in London, and although
      hypertension is more common and more severe in blacks, the proportion of renal
      failure attributed to primary hypertension is overestimated, and the diagnosis is
      often made using inadequate criteria.

PMID- 10922309
TI  - Outcome data on pediatric dialysis patients from the end-stage renal disease
      clinical indicators project.
AB  - Network 1 (New England) initiated the Clinical Indicator Project to survey
      dialysis adequacy (Kt/V), nutrition (serum albumin level), and anemia management
      in patients maintained on chronic dialysis. Because little information is
      available in children, data were specifically recorded covering these variables
      in patients (age, 1 to 18 years) maintained on either hemodialysis (HD) or
      peritoneal dialysis (PD). During the 18 months of data collection, 29
      observations were recorded on 23 HD patients (age, 14.3 +/- 3.6 years), and 43
      observations were made on 30 PD patients (age,10.6 +/- 4.7 years). Kt/V
      correlated inversely with the age of the patient (HD, P < 0.004; PD, P < 0.0007).
      Although serum albumin level was not associated with dialysis adequacy in HD
      patients, there was a strong inverse relationship between albumin level and Kt/V
      in PD patients (P < 0.002). Hematocrit values were not significantly different in
      the two groups (HD, 31.0% +/- 5.5% versus PD, 32.9% +/- 4.8%) and could not be
      correlated with weekly erythropoietin dose. Weekly erythropoietin dose was
      directly related to patient age in both groups (HD, P < 0.05; PD, P < 0.02). The
      weekly erythropoietin dosage needed to maintain the hematocrit was greater in HD
      patients (HD, 11,211 +/- 7,484 U versus PD, 3,790 +/- 1,968 U; P < 0.0001). We
      conclude that (1) smaller children in both groups tend to have a greater Kt/V,
      (2) Kt/V greater than 2.75 in PD patients may not improve nutrition per se and
      could result in increased albumin losses, and (3) erythropoietin dosing appears
      to correlate best with patient size (age) rather than degree of anemia.

PMID- 10922310
TI  - Impact of facility size and profit status on intermediate outcomes in chronic
      dialysis patients.
AB  - Little information is available regarding the influence of dialysis facility size
      or profit status on intermediate outcomes in chronic dialysis patients. We have
      combined data from the Health Care Financing Administration (HCFA) Core
      Indicators Project; the end-stage renal disease (ESRD) facility survey; and the
      HCFA On-Line Survey, Certification, and Reporting System to analyze trends in
      this area. For hemodialysis patients, larger facilities were more likely than
      smaller facilities to perform dialysis on patients who were younger than 65 years
      of age, black, or undergoing dialysis 2 years or more (P < 0.001). Nonprofit
      facilities were more likely to perform dialysis on patients with diabetes
      mellitus as a cause of ESRD and less likely to perform dialysis on patients with
      hypertension as a cause of ESRD compared with for-profit units (P < 0.05). By
      multivariate analysis, larger facility size was modestly associated with a
      greater Kt/V value and urea reduction ratio, but not with hematocrit or serum
      albumin values. Facility profit status was not associated with these intermediate
      outcomes. For peritoneal dialysis patients, there were no significant differences
      in patient demographics based on facility size. More patients in nonprofit units
      had been undergoing dialysis 2 or more years than patients in for-profit units (P
      < 0.05). By univariate analysis, patients in larger facilities were more likely
      to have an adequacy measure performed than patients from smaller facilities (P <
      0.05). There were few substantial differences in intermediate outcomes in chronic
      dialysis patients based on facility size or profit status.

PMID- 10922311
TI  - Formal literature review of quality-of-life instruments used in end-stage renal
      disease.
AB  - Although quality-of-life assessment is an important complement to conventional
      clinical evaluation, there are limited opportunities for researchers in end-stage
      renal disease (ESRD) to examine evidence for a range of quality-of-life measures.
      To better understand how quality of life has been conceptualized, measured, and
      evaluated for ESRD, we conducted a structured literature review. Eligible
      articles were identified from a MEDLINE search, expert input, and review of
      references from eligible articles. A standardized instrument was created for
      article review and included type of measure, instrument development process,
      study sample characteristics, quality-of-life domains, and reliability and
      validity testing. From 436 citations, 78 articles were eligible for final review,
      and of those, 47 articles contained evidence of reliability or validity testing.
      Within this set, there were 113 uses of 53 different instruments: 82% were
      generic and 18% were disease specific. Only 32% defined quality of life. The most
      frequently assessed domains were depression (41%), social functioning (32%),
      positive affect (30%), and role functioning (27%). Testing was completed for test
      retest reliability (20%), interrater reliability (13%), internal consistency
      (22%), content validity (24%), construct validity (41%), criterion validity
      (55%), and responsiveness (59%). Few articles measuring quality of life in ESRD
      defined quality-of-life domains or adequately described instrument development
      and testing. Generic measures, such as the Sickness Impact Profile, and disease
      specific measures, such as the Kidney Disease Questionnaire, had been tested more
      thoroughly than others. Standardized reporting and more rigorous testing could
      help researchers make informed choices about instruments that would best serve
      their own and their patients' needs.

PMID- 10922312
TI  - Vitamin D deficiency is implicated in reduced serum albumin concentrations in
      patients with end-stage renal disease.
AB  - The mortality rate in hemodialysis patients remains extremely high, and reduced
      serum albumin concentration resulting from malnutrition is the strongest
      predictor of mortality and morbidity. Several inflammatory cytokines involved in
      malnutrition, including interleukin-1, interleukin-6, and tumor necrosis factor
      alpha, are modulated by 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], of which
      synthesis is impaired in end-stage renal disease. We evaluated whether 1,25
      (OH)(2)D(3) deficiency might be involved in reduced serum albumin concentrations.
      Fifty-one predialysis uremic patients about to begin hemodialysis therapy were
      divided into groups with serum 1,25-(OH)(2)D(3) concentrations less than 18 pg/mL
      (low-D(3) group; n = 39) and concentrations of 18 pg/mL or greater (normal-D(3)
      group; n = 12). Serum albumin concentrations before the initiation of
      hemodialysis treatment were compared between the two groups. Furthermore, the
      effect of supplementation with active forms of vitamin D during 4 months of
      hemodialysis treatment on serum albumin concentrations was retrospectively
      evaluated in the low-D(3) group. Serum albumin concentrations in the low-D(3)
      group were significantly less than those in the normal-D(3) group (3.58 +/- 0. 50
      versus 3.82 +/- 0.10 g/dL; P = 0.034). Considering all patients, a significant
      positive correlation between serum concentrations of albumin and 1,25-(OH)(2)D(3)
      was noted (r = 0.417; P = 0.0023). Supplementation with active forms of vitamin D
      significantly increased serum albumin concentrations in the low-D(3) group from
      3. 61 +/- 0.12 to 3.79 +/- 0.13 g/dL (P = 0.0067). These findings indicate that
      reductions in serum albumin concentrations may be attributed, at least in part,
      to vitamin D deficiency in patients with end-stage renal disease.

PMID- 10922313
TI  - Clinical performance of a new high-flux synthetic membrane.
AB  - The clinical performance during first use of a new membrane manufactured from a
      blend of polyarylethersulfone and polyvinylpyrrolidone (Arylane; Hospal Renal
      Care, Lyon, France), in which the microstructure of the membrane has been
      tailored by the manufacturing process and polymer blend, has been compared with
      Fresenius Polysulfone (Fresenius Medical Care, Bad Homburg, Germany) in a
      prospective, randomized, crossover study. Small-molecular clearances were
      similar. A reduction in plasma beta(2)-microglobulin levels was present using
      both membranes, with a significantly greater removal by Arylane such that the
      mean postdialysis plasma level difference between the membranes at the end of
      dialysis was 8. 7 mg/L (95% confidence interval, 3.9 to 13.5; P = 0.004).
      Recovery of beta(2)-microglobulin from the dialysis fluid was similar: 170 +/- 70
      mg for Arylane and 110 +/- 60 mg for Fresenius Polysulfone (P = 0.04). Both
      membranes were impermeable to albumin but allowed the passage of low-molecular
      weight proteins, with 10,046 +/- 3,239 mg for Arylane and 7,285 +/- 2,353 mg for
      Fresenius Polysulfone recovered from the dialysis fluid (P = 0.07). Neutropenia
      and platelet adhesion to the membrane were minimal, and time-averaged complement
      levels during dialysis for C3a and C5b-9 were 207 +/- 92 and 62 +/- 24 ng/mL for
      Arylane and 223 +/- 68 and 45 +/- 24 ng/mL for Fresenius Polysulfone,
      respectively, and were membrane independent. This study indicates that the
      membrane using polyarylethersulfone in conjunction with PVP has complement
      activation potential and neutropenia similar to Fresenius Polysulfone but has an
      enhanced capacity to remove beta(2)-microglobulin. This enhanced removal arises
      from transmembrane transport augmented by adsorption within the membrane matrix.

PMID- 10922314
TI  - Isothermic hemodialysis and ultrafiltration.
AB  - The increase in patient temperature during hemodialysis is explained by
      hemodynamic compensation during ultrafiltration and hypovolemia that leads to
      peripheral vasoconstriction and reduced heat losses. We analyzed 51 stable high
      efficiency hemodialysis treatments in 27 patients during isothermic dialysis in
      which body temperature was maintained at a constant level (+/-0.1 degrees C)
      using the temperature-control option of the Blood Temperature Monitor (BTM;
      Fresenius Medical Care, Bad Homburg, Germany). Hemodialysis was delivered using
      ultrapure water (limulus amebocyte lysate test < 0. 06 endotoxin units/mL) at
      mean blood flows of 410 +/- 40 mL/min. During treatments lasting 178 +/- 23
      minutes, 4.8% +/- 1.4% of postdialysis body weight (W%) and 9.5% +/- 2.5% of
      postdialysis body water were removed using mean ultrafiltration rates of 1.1 +/-
      0.3 L/h. Dialysate temperatures significantly decreased from 35.9 degrees C +/-
      0.3 degrees C to 35.6 degrees C +/- 0.6 degrees C during hemodialysis. During
      these treatments, 187 +/- 69 kJ of thermal energy were removed from the patients
      through the extracorporeal circulation using cool dialysate. Extracorporeal heat
      flow was 17 +/- 6 W. Energy expenditure (H) estimated from anthropometric data
      was 65 +/- 12 W. Thus, 28% +/- 10% of estimated energy expenditure (H%) was
      removed during isothermic dialysis. A highly significant correlation was observed
      between H% and W% (H% = -5.6 * W%; r(2) = 0.91; P < 0.0001). This result is in
      support of the volume hypothesis of intradialytic heat accumulation and provides
      a rule of thumb to estimate extracorporeal cooling requirements for isothermic
      dialysis. Approximately 6% of H must be removed through the extracorporeal
      circulation for each percent of ultrafiltration-induced body-weight change. The
      importance of body temperature control during hemodialysis increases with
      increased ultrafiltration requirements.

PMID- 10922315
TI  - High creatinine excretion ratio predicts a good outcome in peritoneal dialysis
      patients.
AB  - The creatinine excretion (CrEx) ratio was first described as a method for
      detecting noncompliance in peritoneal dialysis (PD) patients. However, a high
      CrEx ratio is not specific for noncompliance and may also be found in compliant
      patients with a relatively greater lean body mass (LBM). A cohort of 44 PD
      patients was followed up for a mean of 13 +/- 8 months after measurement of
      baseline CrEx ratio to investigate whether greater values were predictive of good
      or poor clinical outcomes. During this follow-up, 11 patients died, 12 patients
      transferred to hemodialysis, 4 patients underwent transplantation, 1 patient
      recovered renal function, and 16 patients continued on PD. The mean CrEx ratio in
      all patients was 1.14 +/- 0.32. It did not differ between men and women (1.15
      versus 1.13, respectively; P = 0.76) but showed a trend toward being less in
      patients with diabetes (1.03 versus 1.19; P = 0. 19). The mean weekly Kt/V,
      weekly creatinine clearance, normalized protein equivalent of nitrogen
      appearance, and serum albumin values were 2.18 +/- 0.57, 73.57 +/- 33.75 L/1.73
      m(2), 0.80 +/- 0.22 g/kg/d, and 3.22 +/- 0.59 g/dL, respectively. Technique
      failure (P < 0.001) and death (P < 0.05) were significantly more common in
      patients with a CrEx ratio less than 1 compared with those with a CrEx ratio
      greater than 1. On Cox regression analysis, the CrEx ratio was the only
      significant predictor of technique failure and was also an independent predictor
      of death. High CrEx ratio is a predictor of good, rather than poor, outcome in PD
      patients, perhaps because it is primarily an index of nutrition. This further
      weakens the argument that it is a reliable or useful marker of noncompliance.

PMID- 10922316
TI  - Effect of nitrendipine and nisoldipine on renal structure and function in long
      term experimental diabetes in rats.
AB  - This study investigates the efficacy of late intervention with the calcium
      channel blockers (CCBs) nitrendipine and nisoldipine in preventing development of
      albuminuria and glomerular hypertrophy in experimental diabetes. Streptozotocin
      (STZ)-induced diabetic rats were treated with nitrendipine or nisoldipine for 6
      weeks after 3 or 6 months of untreated diabetes. The CCBs were administered in
      the fodder in a concentration of 250 mg/kg. After 3 months of untreated diabetes,
      nitrendipine treatment for 6 weeks significantly reduced urinary albumin
      excretion (UAE; P < 0.05) and glomerular hypertrophy. Nitrendipine also prevented
      an increase in systemic blood pressure compared with untreated diabetes.
      Nisoldipine showed no significant effect on UAE or glomerular hypertrophy despite
      systemic blood pressures similar to those of the diabetic nitrendipine-treated
      group. After 6 months of untreated diabetes, treatment with nitrendipine or
      nisoldipine for 6 weeks did not show effects on UAE, glomerular hypertrophy, or
      systemic blood pressure. No effect was found on renal growth in the treatment
      groups, and neither nitrendipine nor nisoldipine had any effect on body weight,
      blood glucose level, or food intake.

PMID- 10922317
TI  - Ultrastructural appearance of renal and other basement membranes in the Bull
      terrier model of autosomal dominant hereditary nephritis.
AB  - Bull terrier hereditary nephritis may represent a model for autosomal dominant
      Alport's syndrome because affected dogs have the typically lamellated glomerular
      basement membrane (GBM) and father-to-son disease transmission occurs. This study
      examined the ultrastructural appearance of the renal and extrarenal basement
      membranes and their composition in affected Bull terriers. Affected stillborn
      animals and puppies had subepithelial frilling and vacuolation of the GBM. In
      adult dogs, lamellation was common, and subepithelial frilling and vacuolation
      were less prominent. Foot-process effacement and mesangial matrix expansion
      occurred frequently. Basement membranes in the glomeruli, tubules, and Bowman's
      capsule were significantly thickened and often mineralized. Immunohistochemical
      examination showed alpha 1(IV) and alpha 2(IV) collagen chains in all renal
      basement membranes; alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains in the GBM,
      distal tubular basement membrane, and Bowman's capsule; and the alpha 6(IV) chain
      in Bowman's capsule. Conversely, the basement membranes from the affected Bull
      terrier cornea, lens capsule, retina, skin, lung, and muscle had a normal
      ultrastructural appearance and were not thickened compared with membranes in
      normal age-matched dogs. The distribution of basement membrane abnormalities in
      Bull terrier hereditary nephritis may occur because the defective protein is
      present exclusively or more abundantly in the kidney and is structurally more
      important in the kidney or because of local intrarenal stresses.

PMID- 10922318
TI  - Immunoadsorption in Goodpasture's syndrome.
AB  - Patients with Goodpasture's syndrome presenting with dialysis-dependent end-stage
      renal failure at diagnosis almost never regain independent renal function. We
      report a patient with a 100% crescentic lesion in whom reversal of dialysis
      dependence was achieved by immunoadsorption together with immunosuppression. In a
      second patient, early initiation of immunoadsorption was able to completely
      restore normal renal function as early as 1 month after the start of treatment.
      These data give evidence of the use of immunoadsorption as a hopeful alternative
      to conventional plasma exchange in patients with Goodpasture's syndrome showing
      advanced renal failure.

PMID- 10922319
TI  - Waterhouse-Friderichsen syndrome and bilateral renal cortical necrosis in
      meningococcal sepsis.
AB  - Waterhouse-Friderichsen syndrome and bilateral renal cortical necrosis (BRCN) are
      rare complications of meningococcal sepsis associated with high mortality rates.
      We describe a 20-year-old man who presented with a 1-day history of fever,
      chills, malaise, and vomiting. He collapsed in the emergency room, requiring
      mechanical ventilation and intravenous vasopressors for resuscitation. He was
      noted to be anuric, and computed tomography showed adrenal hemorrhage and BRCN.
      Blood cultures later confirmed Neisseria meningitidis sepsis, and a biopsy
      confirmed renal cortical infarction. The patient was treated aggressively with
      intravenous antibiotics, corticosteroids, and immunoglobulins, in addition to
      plasmapheresis, dialysis, and supportive measures. He recovered his adrenal
      function and was discharged from the hospital, but he remains dialysis dependent.
      To our knowledge, this is the first reported case of concomitant Waterhouse
      Friderichsen syndrome and BRCN in a patient with meningococcal sepsis.

PMID- 10922320
TI  - Chlorambucil-induced acute hepatic failure in a patient with membranous
      nephropathy.
AB  - We present the case of a 23-year-old woman with membranous nephropathy who
      developed acute hepatic failure after being administered chlorambucil for a
      month.

PMID- 10922322
TI  - Advancing the cold front.

PMID- 10922321
TI  - Venous thromboembolism in end-stage renal disease.
AB  - Venous thromboembolic disease is considered an uncommon event in the end-stage
      renal disease (ESRD) population. We report five cases of venous thromboembolism
      (VTE) occurring in dialysis patients within a 1-year period at a single center.
      Analysis of these cases and review of the literature suggest that risk factors
      for VTE in the ESRD population are similar to those of the general population.
      Chronically ill, debilitated patients appear to be those most likely to develop
      VTE.

PMID- 10922323
TI  - Chronic renal confusion: insufficiency, failure, dysfunction, or disease.
AB  - The terms routinely used to describe states of reduced glomerular filtration rate
      (GFR) not requiring renal replacement therapy are poorly defined. With increasing
      interest in the epidemiology of chronic renal insufficiency and the timing of
      initiation of dialysis, terms such as "pre-ESRD" and "pre-dialysis" have been
      popularized, again without clear definition. Unambiguous terminology should be
      adopted. The authors favor using the term chronic renal insufficiency to describe
      states of reduced GFR not severe enough to require dialysis or transplantation.
      The authors propose classifying patients with GFR of 60 to 41 mL/min, 40 to 21
      mL/min, and 20 mL/min or below as having mild, moderate, and advanced degrees of
      chronic renal insufficiency, respectively. The use of this terminology will
      facilitate communication among nephrologists and other physicians and provide a
      framework for comparison of populations across cohort studies and clinical
      trials.

PMID- 10922325
TI  - Angiotensin II: an immune costimulator?

PMID- 10922324
TI  - Renal biopsy in high-risk patients with medical diseases of the kidney.
AB  - The number of high-risk patients undergoing renal biopsy is likely to increase in
      the near future because of the increased use of anticoagulants for such
      conditions as atrial fibrillation, combined liver and kidney disease caused by
      hepatitis C, and the aging of the population. Nephrologists need to become
      increasingly familiar with evaluating such patients through both specialized
      management of percutaneous kidney biopsy and alternate methods of renal biopsy,
      which primarily consist of open (surgical) biopsy, transjugular (transvenous)
      biopsy, and laparoscopic biopsy. The indications, complications, and general
      approach to such patients are discussed. This is a US government work. There are
      no restrictions on its use.

PMID- 10922326
TI  - An 18-year-old female with acute onset of nephrotic syndrome.

PMID- 10922327
TI  - Biological scaling and Kt/V: additional aspects.

PMID- 10922328
TI  - Cytomegalovirus infection

PMID- 10922329
TI  - Continuing medical education exercise, august 2000

PMID- 10922330
TI  - D-lactic acidosis 23 years after jejuno-ileal bypass.
AB  - Accumulation of D-lactate after gastrointestinal surgery, particularly jejuno
      ileal bypass, is an uncommon and often misdiagnosed clinical disturbance. The
      syndrome may be complicated by dizziness, ataxia, confusion, headache, memory
      loss, and aggressive behavior. Serum chemistries are often deceptive because the
      anion gap is frequently normal in spite of severe metabolic acidosis. Moreover,
      the urine anion gap may be positive, incorrectly suggesting a defect in renal net
      acid excretion. Indeed, the combination of a normal anion gap metabolic acidosis
      and positive urine anion gap may erroneously suggest a diagnosis of renal tubular
      acidosis. Importantly, all reported cases of D-lactic acidosis secondary to
      bypass surgery have been encountered within 5 to 10 years following the surgery.
      Here we present an unusual case of D-lactic acidosis (complicated by
      encephalopathy) presenting 23 years after a jejuno-ileal bypass procedure. The
      patient was initially diagnosed with a drug intoxication secondary to
      benzodiazepines. Ultimately, the diagnosis of D-lactate encephalopathy was
      established after challenging the patient with a carbohydrate load. Thus,
      administration of 40 kcal/kg over 16 hours reproduced the clinical syndrome and
      was accompanied by a marked increment in serum and urine D-lactate concentration.
      The patient had sustained resolution of her symptoms after treatment with oral
      vancomycin.

PMID- 10922331
TI  - Acute renal failure after a sea anemone sting.
AB  - A 27-year-old man suffering from severe swelling and pain in his right arm was
      referred to our hospital. He showed signs of acute renal failure (ARF) with
      severe dermatitis of his right arm. Three days before being admitted, he
      accidentally touched some kind of marine organism with his right hand while
      snorkeling in the Sulu Sea around Cebu Island. Within a few minutes, he was
      experiencing severe pain in his right hand. Then his right hand gradually became
      swollen. The marine creature responsible for this injury was thought to have been
      a sea anemone, which is a type of coelenterate. Histologic findings of a renal
      biopsy indicated that acute tubular necrosis (ATN) had caused ARF in this
      patient's case. Supportive therapies improved renal function of this patient, and
      steroid pulse therapy attenuated the severe skin discoloration. The ATN was
      thought to have been caused by the poison from a sea anemone because there were
      no other conceivable reasons for the patient's condition. This is the first time
      that a marine envenomation case has been reported in which the sting of a sea
      anemone has caused ATN without the failure of any other organs.

PMID- 10922332
TI  - Hemoperitoneum in patients receiving hemodialysis.
AB  - Acute abdominal pain in chronic hemodialysis patients has well-known causes,
      including acute pancreatitis, mesenteric arterial insufficiency, or complicated
      duodenal ulcer. Others, such as hemoperitoneum, are far less common. Although
      hemoperitoneum occurs in patients receiving peritoneal dialysis, dialysis is
      seldom if ever the direct cause of the bleeding. Hemoperitoneum is often related
      to menses or ovulation, particularly to ovarian cyst rupture; therefore, it is
      more common in young women. In most cases, no specific treatment is required.
      Hemoperitoneum is rarely considered as the cause of acute abdominal pain in
      chronic hemodialysis patients. In this report of hemoperitoneum confirmed by
      emergency laparotomy in 3 women, bleeding was not related to gynecologic origin.
      All of the women were younger than age 50 and undergoing long-term hemodialysis.
      All patients had a history of acute abdominal pain associated with shock. The
      cause of bleeding was always an organ lesion: hepatic amyloidosis with suspected
      portal hypertension or sclerosing peritonitis and acute hemorrhagic pancreatitis.
      Coagulation abnormalities and the use of anticoagulants during hemodialysis
      sessions may have been aggravating factors in all three patients. Hemoperitoneum
      is difficult to diagnose, particularly in the minor forms, and consequently its
      incidence may be underestimated. Therefore, it should be considered whenever a
      chronic hemodialysis patient presents with persistent acute abdominal pain.

PMID- 10922333
TI  - Overcorrection of hyponatremia: where do we go wrong?
AB  - Predicted sodium concentrations [Na(+)] based on traditional calculations for the
      correction of hyponatremia often do not match treated [Na(+)], for various
      reasons. In many situations, hyponatremia is corrected at unexpectedly rapid
      rates. The authors present an analysis of two cases of overly rapid correction of
      hyponatremia despite apparently appropriate management based on initial
      evaluations. The mistakes involved are discussed and simple calculations
      demonstrated to prove that the overcorrections did not occur at random.
      Overcorrection in one case involved miscommunications between the emergency room
      and admitting physicians regarding the amount of saline and potassium already
      administered to the patient. Unexpected hypoosmotic polyuria was responsible for
      overcorrection in the other case. Overcorrection of hyponatremia may be
      preventable in many cases. In general, overcorrection of hyponatremia is caused
      by either "too much salt (Na(+) + K(+)) gained" or "too much water lost."
      Recognizing common pitfalls will enable physicians to avoid overcorrection and
      its attendant risk of fatal osmotic demyelinating syndrome (ODS).

PMID- 10922334
TI  - Plasmapheresis in the treatment of glomerulonephritis: indications and
      complications.

PMID- 10922335
TI  - Tobacco habits and risk of lung, oropharyngeal and oral cavity cancer: a
      population-based case-control study in Bhopal, India.
AB  - BACKGROUND: Tobacco habits in India are unique and vary in different regions. Few
      studies, and none from central India, have reported on type of tobacco used and
      risk of the most common cancer types in India. We conducted a population-based
      case-control study to evaluate the risk of tobacco particularly bidi smoking and
      tobacco quid chewing on the most common cancer sites among males in Bhopal.
      METHODS: In all, 163 lung, 247 oropharyngeal and 148 oral cavity cancer cases
      from the Population-Based Cancer Registry records and 260 controls randomly
      selected from a tobacco survey conducted in the Bhopal population formed the
      study population. RESULTS: A significant risk of bidi and cigarette smoking with
      a dose-response relationship was observed for lung and oropharyngeal cancer.
      Tobacco quid chewing showed no risk for lung, marginally increased risk for
      oropharyngeal and about a sixfold increased risk for oral cavity cancer.
      Population-attributable risk per cent (PARP) was observed to be 82.7% and 71.6%
      for smokers for the development of lung and oropharyngeal cancer, while the same
      was found to be 66.1% for tobacco chewers for the development of oral cavity
      cancer. CONCLUSIONS: These data provide strong evidence that smoking bidi is even
      more hazardous than cigarette smoking in the development of lung and
      oropharyngeal cancer. An intervention study to prevent the use of tobacco will be
      useful in this population as it also underwent gas exposure due to a chemical
      accident in 1984.

PMID- 10922336
TI  - Fish consumption is inversely associated with male lung cancer mortality in
      countries with high levels of cigarette smoking or animal fat consumption.
AB  - BACKGROUND: A striking difference in fish consumption and lung cancer mortality
      (LCM) exists among populations worldwide. This study investigated the relation
      between fish consumption and LCM at the population level. METHODS: Sex-specific
      LCM data, mostly around 1993 and fish consumption data for 10 periods 1961-1994
      in 36 countries were obtained from WHO and FAO, respectively. RESULTS: A
      significant inverse correlation exists between log fish consumption and LCM rate
      in 9 out of the 10 time periods (r = -0.34 to r = -0.46, P = 0.044 to P = 0.005).
      After adjusting for smoking and other confounders, log fish consumption (% of
      total energy [% E]) was inversely and significantly associated with LCM rate (per
      100 000 per year) in all 10 time periods (beta = -26.3 to beta = -36.7; P =
      0.0039 to P < 0.0001). The stratified analysis showed that this inverse relation
      was significant only in countries with above median level of smoking (>2437
      cigarettes/adult/year) or animal fat minus fish fat consumption (22.4% E). An
      increase in fish consumption by 1% E was calculated to reduce mean male LCM rate
      of the populations examined in the age class of 45-74 years by 8.4%. In women, no
      significant relation between fish consumption and LCM could be established.
      CONCLUSIONS: Fish consumption is associated with a reduced risk from LCM, but
      this possible protective effect is clear-cut only in men and in countries with
      high levels of cigarette smoking or animal fat consumption.

PMID- 10922337
TI  - A prospective study of job strain and risk of breast cancer.
AB  - BACKGROUND: There is conflicting evidence on whether stress is a risk factor for
      breast cancer. The present study examined prospectively the relationship between
      stress at work and risk of breast cancer. METHODS: Participants comprised 26 936
      postmenopausal women in the Nurses' Health Study ages 46-72 who were in paid
      employment, and who had no previous history of cancer. Multivariate-adjusted
      regression analysis was used to examine the relationship between job strain
      (measured by the Karasek Job Content Questionnaire in 1992) and risk of incident
      invasive and in situ breast cancer. RESULTS: From 1992 through 1994, 219 women
      were diagnosed with breast cancer. No evidence was found for a relationship
      between job stress and risk of breast cancer. Compared with women in low strain
      jobs, the multivariate-adjusted relative risks of breast cancer were RR = 0.78
      (95% CI : 0.52-1.16) for high-strain jobs; RR = 0.76 (95% CI : 0.49-1.17) for
      active jobs; and RR = 0.94 (95% CI : 0.67-1.34) for passive jobs. Although job
      strain was related to less breast cancer screening among women in highly
      demanding jobs, it was not associated with tumour size. CONCLUSIONS: Job stress
      was not related to an increase in the incidence of breast cancer in the present
      cohort of nurses.

PMID- 10922338
TI  - High-risk mammographic parenchymal patterns, hormone replacement therapy and
      other risk factors: a case-control study.
AB  - BACKGROUND: Mammographic parenchymal patterns are of particular interest because
      the denser patterns reduce screening sensitivity as well as increasing breast
      cancer risk, and because they have been shown to be affected by exogenous
      oestrogens. METHODS: We designed a case-control study comprising 200 cases with
      high-risk (P2 and DY) pattern and 200 controls with low-risk (N1 and P1) pattern.
      Mammograms were evaluated according to the Wolfe classification. RESULTS: Parity,
      body mass index (BMI) and current smoking were inversely and independently
      associated, whereas late age of menarche and history of benign breast disease
      were positively associated with high-risk mammographic patterns. Current-users of
      hormone replacement therapy (HRT) were more than twice as likely to have a high
      risk pattern than never-users (OR = 2.48, 95% CI : 1.32-4.61). Women who used HRT
      for more than 5 years were almost three times more likely to have a high-risk
      pattern than never-users (OR = 2.77, 95% CI : 1.11-6.91). Relative to never
      users, women who started HRT before the menopause were more than twice as likely
      to have a high-risk pattern (OR = 2.53, 95% CI : 1.31-4.87). CONCLUSIONS: Careful
      clinical and mammographical follow-up might be appropriate in women undergoing
      HRT. The HRT-induced mammographic pattern might be regarded as a new baseline and
      changes with respect to this new pattern could then be monitored over time.

PMID- 10922339
TI  - Risk factors for benign proliferative breast disease.
AB  - BACKGROUND: As part of a nested case-control study of benign proliferative breast
      disease (BPBD) conducted within the cohort of women participating in the Alberta
      breast screening programme, an analysis of all women who had a benign breast
      biopsy between 1990 and 1995 was undertaken to identify the epidemiological risk
      factors for BPBD. METHODS: The breast biopsies of all eligible women were re
      reviewed by a panel of four pathologists using Page's classification for benign
      breast disease. Cases were 165 women whose biopsies, upon review, showed benign
      breast tissue changes ranging from sclerosing adenosis to atypical ductal
      hyperplasia. Controls were 217 women whose biopsies showed no evidence of any
      proliferative or neoplastic changes. In-person interviews were conducted with all
      study subjects. RESULTS: Women with >/=25% fibroglandular breast tissue density,
      as compared to women with <25% density, experienced nearly a doubling in risk of
      BPBD (OR = 1.91, 95% CI : 1.24-2.94). All other possible risk factors examined
      were not associated with BPBD. CONCLUSION: This study suggests that
      fibroglandular tissue density may be a risk factor, or marker, for increased risk
      of BPBD.

PMID- 10922340
TI  - Trends in incidence of adenocarcinoma of the oesophagus and gastric cardia in ten
      European countries.
AB  - BACKGROUND: In many western countries an increase in incidence of adenocarcinoma
      of the oesophagus and/or gastric cardia have been reported. The aim of this study
      was to describe and compare trends in incidence of adenocarcinoma of the
      oesophagus and gastric cardia in several areas of Europe, 1968-1995, using
      Eurocim (a database of cancer incidence and mortality data from 95 European
      cancer registries). METHODS: Time-trends in age-standardized incidence rates of
      adenocarcinomas of the oesophagus and gastric cardia are described in 11
      population-based cancer registries from 10 countries in North, South, East, West
      and Central Europe, 1968-1995. The statistical significance of the time-trends in
      incidence was assessed using Poisson regression analysis. RESULTS: An increase in
      incidence of adenocarcinomas of the oesophagus and gastric cardia was observed in
      Northern Europe (Denmark), Southern Europe (Italy, Varese), Eastern Europe
      (Slovakia) and Western Europe (England and Wales, Scotland). In Central Europe
      (Switzerland, Basel) and in the cancer registries of Iceland (Northern Europe),
      France, Bas-Rhin and Calvados, Southern Ireland, and the Netherlands, Eindhoven
      (Western Europe) no rise in incidence was observed. The increase in incidence of
      adenocarcinomas of the oesophagus and gastric cardia was accompanied by a
      decrease in incidence of both adenocarcinomas and non-adenocarcinomas of the non
      cardia part of the stomach in almost all of the 11 cancer registries studied.
      Increased histological verification of tumours of the oesophagus and stomach and
      improvement in precision of histological diagnosis may partly explain the
      increase in incidence of adenocarcinomas in some registries. CONCLUSIONS: This
      study, using Eurocim data, supports the findings from other time-trend studies of
      population-based cancer registries in western countries.

PMID- 10922341
TI  - Quantifying the association between habitual energy expenditure and blood
      pressure.
AB  - BACKGROUND: Previous studies have demonstrated an association between physical
      inactivity and hypertension, but the methods used to assess activity have been
      subjective and imprecise. Recently methods have become available allowing
      measurement of energy expenditure in free-living populations. Our aim was to
      employ these methods to assess the independent association between energy
      expenditure, cardio-respiratory fitness and blood pressure. METHODS: In a cross
      sectional study of 775 people (45-70 years) participating in a continuing
      population-based cohort study, energy expenditure was assessed by 4 days of heart
      rate monitoring with individual calibration of the relationship between heart
      rate and energy expenditure, a method validated against doubly-labelled water and
      whole body calorimetry. Cardio-respiratory fitness was assessed in a sub-maximal
      test. To adjust for measurement error in the assessment of usual energy
      expenditure and fitness, 190 subjects repeated both tests on three further
      occasions at 4-monthly intervals. RESULTS: A highly significant linear trend in
      blood pressure was found across quintiles of the physical activity level, the
      ratio of total energy expenditure to basal metabolic rate. The differences in the
      mean systolic/diastolic blood pressure between the top and bottom quintile was
      6.3/4.4 mmHg in men and 10.7/5.9 mmHg in women. These effects were independent of
      obesity and cardio-respiratory fitness. Correction for measurement error suggests
      that the true underlying relationship between usual energy expenditure and blood
      pressure is stronger still. CONCLUSIONS: These findings are compatible with a
      strong association between usual energy expenditure and blood pressure and
      support public health strategies aimed at increasing overall energy expenditure.

PMID- 10922342
TI  - Relationship between intraocular pressure and obesity in Japan.
AB  - BACKGROUND: Some cross-sectional studies have suggested that age, systolic blood
      pressure and obesity are positively related to intraocular pressure (IOP), but
      few longitudinal studies have examined this relationship. This study was carried
      out to evaluate the association between intraocular pressure and obesity by cross
      sectional and longitudinal analyses in a large Japanese population. METHODS: Data
      were collected from annual health examinations between 1989 and 1997 and reviewed
      retrospectively. Subjects of the cross-sectional analysis were 70 139 males and
      females aged 14-94 years. Among these subjects, 25 216 males and females who had
      undergone IOP measurements more than three times were analysed longitudinally.
      The association between IOP and obesity was examined cross-sectionally and
      longitudinally. RESULTS: Cross-sectional analysis: The mean IOP at the last visit
      was 11.6 mmHg. The IOP decreased gradually with age and was significantly higher
      in males than in females in almost all age groups. Body mass index (BMI)
      significantly correlated with IOP after controlling for age, gender and blood
      pressure. Longitudinal analysis: There was a significant association between
      longitudinal change in IOP and change in weight. This relationship remained
      significant after controlling for initial BMI, initial blood pressure, change in
      blood pressure, gender and age. CONCLUSION: This study showed a significant
      association between IOP and obesity in both cross-sectional and longitudinal
      analysis. These findings suggest that obesity is an independent risk factor for
      increase in IOP.

PMID- 10922343
TI  - Alcohol and survival in the Italian rural cohorts of the Seven Countries Study.
AB  - BACKGROUND: Middle-aged men who regularly drink a moderate amount of alcohol have
      lower mortality rates from all causes in comparison with abstainers and heavy
      drinkers. This cohort study looks at the relationship between alcohol consumption
      and long-term survival, adjusting for smoking habit and physical activity.
      METHODS: In 1965, a total of 1536 Italian males aged 45-65 years underwent an
      examination which included: a general questionnaire, anthropometric measurements,
      an overall physical examination, ECG recording, blood pressure and serum
      cholesterol measurements and measurement of food consumption including alcohol.
      The cohort was followed for total mortality from 1965 to 1995. RESULTS: During a
      period of 30 years 1096 deaths occurred. Age-adjusted life expectancy for men
      assuming a mean daily quantity of 63 g of alcohol (range 4-7 drinks per day) was
      21.6 +/- 0.4 years, roughly 2 years more than men taking a mean quantity of 3.7 g
      (</=1 drink) and men consuming >10 drinks per day. Taking smoking habit into
      account, the longest survival of 22.4 +/- 0.5 years was observed in non-smokers
      drinking 4-7 drinks daily; the lowest, 18.5 +/- 0.7 years, in smokers drinking
      >10 drinks. Stratifying for physical activity, the longest survival (23.4 +/- 0.
      7 years) was experienced by men engaged in heavy physical activity at work
      drinking 1-4 drinks per day. CONCLUSIONS: The relationship between life
      expectancy and alcohol consumption (97% wine in this Italian cohort and mostly
      red wine) is confirmed to be non-linear. Men aged 45-64 at entry drinking about 5
      drinks per day have a longer life expectancy than occasional and heavy drinkers.

PMID- 10922344
TI  - Menstruation and reproduction in women with polychlorinated biphenyl (PCB)
      poisoning: long-term follow-up interviews of the women from the Taiwan Yucheng
      cohort.
AB  - BACKGROUND: In 1979 in Taiwan, about 2000 people were poisoned by cooking oil
      contaminated with heat-degraded polychlorinated biphenyls (PCBs). Victims
      developed chloracne and other symptoms; the illness is called Yucheng (oil
      disease). The chemicals persist in the victims' bodies and some are toxic to the
      female reproductive system in experimental animals. METHODS: In 1993-1994, we
      identified the living Yucheng women and neighbourhood controls and interviewed
      them about their reproductive experience. Of the 596 living Yucheng women aged 30
      59 years, we found 368, and interviewed 356. We identified 329 controls, and
      interviewed 312. RESULTS: Of the Yucheng women, 16% reported abnormal menstrual
      bleeding compared to 8% (P < 0.05) of control women; 4.2% versus 1.7% reported a
      stillbirth since 1979 (P = 0.068). Other characteristics of the menses,
      fertility, frequency of intercourse, and age at menopause appeared unaffected.
      More of the Yucheng women reported that one of their offspring had died during
      childhood (10.2% versus 6.1%, P < 0. 05), and that they had decided to limit
      childbearing because of health problems (7% versus 2%, P = 0.01). CONCLUSIONS:
      These findings suggest that high level PCB/polychlorinated dibenzofuran (PCDF)
      exposure has some effect on female endocrine and reproductive function.

PMID- 10922345
TI  - Postneonatal and child mortality among twins in Southern and Eastern Africa.
AB  - BACKGROUND: Few studies have evaluated the difference in mortality between twins
      and singleton children during the postneonatal and childhood period in sub
      Saharan Africa. The aim of this study was to quantify the excess mortality of
      twins during the postneonatal and childhood period and to identify factors that
      contribute to the excess mortality among twins. The different use made of health
      care services was hypothesized to contribute to the increased mortality. METHODS:
      The Demographic and Health Survey data on Malawi, Tanzania and Zambia were
      pooled. Logistic regression was used to estimate twin/singleton differences for
      the combined postneonatal and child mortality and to study the role of
      intermediate factors and effect modifiers. RESULTS: The study was based on 18 214
      singleton children and 706 twins. The twin/ singleton odds ratio (OR) of the
      combined postneonatal and child mortality was 2.33 (95% CI : 1.85-2.93). This
      excess mortality was largest during the first year of life. Control for
      intermediate factors (preventive health care and breastfeeding) did not sizeably
      diminish the mortality difference. Effect modifiers that were associated with
      increased twin/singleton OR were male sex, unwanted child, short birth interval
      and low socioeconomic status. CONCLUSIONS: The excess mortality of twins compared
      to singletons is considerable. A difference in use of preventive health care or
      in breastfeeding cannot explain the increased mortality. Males, unwanted
      children, those born after a short birth interval and the socioeconomically
      disadvantaged are at special risk. The generally good attendance at under-5
      clinics gives health care providers the opportunity for increased surveillance of
      these high-risk groups.

PMID- 10922346
TI  - Survey into health problems of elderly people: a comparison of self-report with
      proxy information.
AB  - BACKGROUND: This study was conducted as part of the Medical Research Council
      Cognitive Function and Ageing Study. OBJECTIVE: To compare information given by
      elderly people on their past and current health and family history of illness
      with similar information obtained from a relative, friend or carer. DESIGN:
      Screening and assessment stages of a prevalence study. SETTING: Three urban and
      two rural areas of England and Wales. PARTICIPANTS: A subsample weighted by age
      and cognitive status of random population samples of people >/=65 years, living
      in their own home or in a residential or nursing home, interviewed between 1991
      and 1994. A relative, friend or carer identified by each elderly person to
      provide proxy information. INTERVIEW: Computerized schedules including items on
      demographic details, cognitive function, lifetime illnesses, current health
      problems and family history of illness. RESULTS: The rate of proxy 'don't know'
      responses and the agreement between the elderly person and their proxy were
      calculated for each item, both for the overall sample and for subgroups based on
      characteristics of the respondent and of the proxy and on the relationship
      between them. Higher 'don't know' rates were found to be particularly associated
      with more distant relationships, questions on family history, a shorter length of
      time known and a lack of co-residence. Agreement was strongly related to the
      nature of the question and less to co-residence, with other factors such as
      relationship having much smaller effects. CONCLUSIONS: Proxy information on past
      and current health problems can be almost complete and in good agreement with
      self-report, particularly where the proxy lives with the respondent. On family
      history of illness, history of head injury or boxing and current sleep problems,
      proxy information is likely to be less complete and show poor agreement. A proxy
      who is not a close relative is likely to give less complete information but
      agreement will not be substantially lower.

PMID- 10922347
TI  - Survey into health problems of elderly people: multivariate analysis of
      concordance between self-report and proxy information.
AB  - BACKGROUND: In many cases probands are unable to give information about their own
      history. Our objective was to compare information given by elderly people on
      their past and current health and family history of illness with similar
      information given by a relative, friend or carer. MATERIAL: In three urban and
      two rural areas of England and Wales a sub-sample, weighted by age and cognitive
      status, was drawn from random population samples of people aged >/=65, not
      permanently living in hospital, and interviewed between 1991 and 1994, plus for
      each of these a relative, friend or carer. METHODS: The relation between the
      reports of probands and informants on cognitive function, lifetime illnesses,
      current health problems, and family history of illness was analysed using
      multiple regression of agreement, measured using Cohen's kappa, and logistic
      regression of bias and of proportion of 'not known' responses. Potential
      explanatory variables used were: centre, proband cognitive function, proband sex,
      informant sex, proband age, difference in age (generation), relationship,
      frequency of contact, period known, modality of informant interview. RESULTS:
      Overall agreement per interview measured by kappa between informant and proband
      was lower for older probands, probands who were cognitively impaired, and those
      who saw one another less often; each effect adjusted for all the others using
      multiple regression. Informants tended to over-report relative to probands if the
      proband was cognitively impaired, male, they themselves were female, of a younger
      generation, and co-resident; each effect adjusted for all the others using
      logistic regression. Interviews were more likely to be missing at least one item
      if the informant was not the spouse, had known the proband for less time, and was
      not co-resident; each effect adjusted for all the others using logistic
      regression. CONCLUSION: There is reasonable accord between probands and
      informants which is enhanced by close contact, long period of knowledge, and a
      female informant. Degree of kinship is not critical. Informant interviews may be
      conducted by telephone rather than face-to-face without serious loss of quality.

PMID- 10922348
TI  - Very old drivers: findings from a population cohort of people aged 84 and over.
AB  - BACKGROUND: Increases in longevity will involve a significant increase among the
      number of drivers in the very old, who are at greater risk of being involved in
      road accidents. Data are thus needed from studies of older populations to
      characterize those still driving, the reasons for giving up and to help formulate
      appropriate policies for dealing with the problems faced and created by an
      increase in older drivers. METHODS: A driving questionnaire was administered to
      surviving members of a cohort comprising a representative sample of individuals
      aged >/=84, the Cambridge City over 75 Cohort. Out of 546 survivors 404 completed
      the driving questionnaire at the 9-year follow-up. In addition, subjects were
      assessed, at baseline and at each follow-up, for cognitive performance using the
      Mini-Mental State Examination (MMSE) and for physical impairment using the
      Instrumental of Activities in Daily Living (IADL) scale. RESULTS: Of the sample,
      37% had driven in the past, and 8.4% were still driving, the majority regularly.
      The drivers tended to be younger (mean age 86.6 years), men (71%) and to be
      married (67.7%). Although physical disability and cognitive impairment are common
      in this age group, current drivers had few physical limitations on their daily
      activities and were not impaired on MMSE. None of the current drivers had visual
      impairment and 22.6% had hearing loss. Of those who had given up driving, 48.5%
      had given up at the age of >/=80. The commonest reasons for giving up driving
      were health problems (28.6%), and loss of confidence (17.9%). One-third reported
      giving up driving on advice. CONCLUSION: A process of self-selection takes place
      among older drivers. People over the age of 84 who are still driving have
      generally high levels of physical fitness and mental functioning, although some
      have some sensory loss. Given the likely increase in the number of older drivers
      over the next decades, safety will be improved most by strategies aimed at the
      entire driving population with older drivers in mind, rather than relying on
      costly screening programmes to identify the relatively small numbers of impaired
      older people who continue to drive.

PMID- 10922349
TI  - A-bomb survivors: factors that may lead to a re-assessment of the radiation
      hazard.
AB  - BACKGROUND: The study cohort of the survivors of the A-bombs in Japan, used as
      the basis of the internationally accepted estimates of cancer radiation risk, was
      collected more than 5 years after the bombing and did not include those who died
      of bomb-related injuries before that date. This paper tests whether the people
      who survived, in spite of bomb-related injuries, are homogeneous in respect of
      variation of cancer risk with age with survivors without such injuries. METHODS:
      Appropriate statistical models are derived and fitted to survivor data by maximum
      likelihood and the resultant statistics used to test the homogeneity assumption.
      RESULTS: Significant differences were found between those with no injuries and
      those with multiple injuries and shown to be largely due to exposures before 10
      or after 55 years of age having exceptionally high risks of late effects of
      radiation for survivors showing early effects, i.e. bomb-related injuries.
      CONCLUSIONS: Certain accepted dogmas about the biology of radiation risks in
      humans, such as 'cancer is the only late effect of radiation' and 'leukaemia is
      uniquely radiogenic amongst cancers', may be significantly in error. These are
      discussed.

PMID- 10922351
TI  - An introduction to instrumental variables for epidemiologists.
AB  - Instrumental-variable (IV) methods were invented over 70 years ago, but remain
      uncommon in epidemiology. Over the past decade or so, non-parametric versions of
      IV methods have appeared that connect IV methods to causal and measurement-error
      models important in epidemiological applications. This paper provides an
      introduction to those developments, illustrated by an application of IV methods
      to non-parametric adjustment for non-compliance in randomized trials.

PMID- 10922350
TI  - Cross-national comparison of injury mortality: Los Angeles County, California and
      Mexico City, Mexico.
AB  - BACKGROUND: Cross-national comparisons of injury mortality can suggest possible
      causal explanations for injuries across different countries and cultures. This
      study identifies differences in injury mortality between Los Angeles (LA) County,
      California and Mexico City DF, Mexico. METHODS: Using LA County and Mexico City
      death certificate data for 1994 and 1995, injury deaths were classified according
      to the International Classification of Diseases Ninth Revision-Clinical
      Modification external cause of injury codes. Crude, gender-, and age-adjusted
      annual fatality rates were calculated and comparisons were made between the two
      regions. RESULTS: Overall and age-adjusted injury death rates were higher for
      Mexico City than for LA County. Injury death rates were found to be higher for
      young adults in LA County and for elderly residents of Mexico City. Death rates
      for motor vehicle crashes, falls, and undetermined causes were higher in Mexico
      City, and relatively high rates of poisoning, homicide, and suicide were found
      for LA County. Motor vehicle crash and fall death rates in Mexico City increased
      beginning at about age 55, while homicide death rates were dramatically higher
      among young adults in LA County. The largest proportion of motor vehicle crash
      deaths was to motor vehicle occupants in LA County and to pedestrians in Mexico
      City. CONCLUSIONS: These findings illustrate the importance of primary injury
      prevention in countries having underdeveloped trauma care systems and should aid
      in setting priorities for future work. The high frequency of pedestrian
      fatalities in Mexico City may be related to migration of rural populations,
      differing vehicle characteristics and traffic patterns, and lack of safety
      knowledge. Mexico City's higher rate of fall-related deaths may be due to
      concurrent morbidity from chronic conditions, high-risk environments, and delay
      in seeking medical treatment.

PMID- 10922352
TI  - Have lessons been learned from the UK bovine spongiform encephalopathy (BSE)
      epidemic?
AB  - History is full of examples of public health, commerce and politics in conflict.
      In recent years attempts to protect UK egg producers, after the discovery of
      Salmonella enteritidis (phage type 4) in hens' eggs, strained previously good
      working relationships between medical and veterinary epidemiologists and ended
      the political career of a government minister who spoke out in defence of the
      public health. Against the background lessons of earlier high profile public
      health problems in the UK conflict should have been avoided when bovine
      spongiform encephalopathy (BSE) started. It might have been expected that its
      significance for human health could have been recognized and researched earlier.
      Public announcements about it could have been timely and clear. Unfortunately
      this was not the case and it looks as though similar mistakes are going to be
      repeated over genetically modified foods.

PMID- 10922353
TI  - Women, drugs and HIV/AIDS: results of a multicentre European study.
AB  - BACKGROUND: In the light of rising human immunodeficiency virus (HIV) incidence
      rates amongst women in Western Europe, a multicentred, cross-sectional study was
      undertaken to explore the multitude of possible factors associated with HIV in a
      population of female injecting drug users (IDU). METHODS: Face-to-face interviews
      were conducted with 1198 female IDU recruited from a variety of settings in
      Paris, Madrid, Rome, London and Berlin. Their HIV status was determined from
      antibody testing of blood or saliva samples or from written confirmation of HIV
      test results from a physician. A hierarchical logistic regression model was used
      to identify direct and indirect associations between socioeconomic factors,
      marginalization and risk behaviour with HIV prevalence. RESULTS: The HIV
      prevalence in the sample of female IDU was 27.8% (range: 1.4% in London and 52.6%
      in Madrid). Factors independently associated with HIV prevalence in the
      regression analysis included: age >25 years (OR = 2.0-2.9), left full-time
      education before age 14 (OR = 2.4), no fixed address (OR = 2.2), previous
      imprisonment (OR = 1.4), commercial sex (OR = 1.3), having a regular HIV positive
      sexual partner (OR = 6.6), ever shared needles (OR = 1.5) and any sexually
      transmitted disease (STD) infection in the last year (OR = 1.7). CONCLUSIONS: The
      sexual behaviour and partners of female IDU in Western Europe are as important a
      component in explaining the HIV epidemic in this population as other risk
      factors, including high-risk drug taking behaviour. Homeless IDU women may be an
      important residual risk group warranting future preventive interventions and
      women with a history of STD should be a particular target for health education.
      Differences in HIV prevalence across cities are very large and may be related to
      differences in harm reduction policies.

PMID- 10922354
TI  - A mathematical model of hepatitis B virus transmission and its application for
      vaccination strategy in china.
AB  - BACKGROUND: Before universal infant immunization against hepatitis B virus (HBV)
      in 1986 China was a region endemic for HBV infection. The prevalence of HBV
      infection in the population was about 60% and the proportion of chronic HBV
      carriers around 10%. These HBV carriers could progress to chronic hepatitis B,
      cirrhosis, and primary hepatocellular carcinoma. Since 1976, large-scale sero
      surveys of HBV infection have been carried out and a lot of data have been
      collected. METHOD: This paper describes a mathematical model developed to predict
      the dynamics of HBV transmission and to evaluate the long-term effectiveness of
      the vaccination programme. We used a compartment model expressed by a set of
      partial differential equations based on the characteristics of HBV infection.
      RESULTS: All parameters, expressed in the model as a non-linear function of age
      and time since vaccination, were estimated using sero-survey data. The model fits
      well with both pre-vaccination and post-vaccination sero-surveys. The observed
      and estimated age-specific prevalence rates of HBV infection and HBV carriage
      agree with each other. According to our model, if all newborns are vaccinated
      according to schedule, the rate of HBV carriage will decline sharply over time to
      0.2% in 70 years. By then, the ratio of acute hepatitis B will be less than 0.5%
      and the ratio of chronic hepatitis B will be around 5%. CONCLUSIONS: The results
      suggest that HBV infection in China can be controlled in just one generation, and
      eventually eliminated. Our model shows that vaccination coverage is the most
      important indicator for the elimination of HBV transmission. The higher the
      vaccination coverage, the better the long-term effectiveness of immunization.
      Thus, the key to controlling and eliminating HBV transmission in China is to find
      ways to immunize all infants throughout the country, especially in poor, rural
      areas.

PMID- 10922355
TI  - Estimation of the indirect effect of Haemophilus influenzae type b conjugate
      vaccine in an American Indian population.
AB  - BACKGROUND: Oropharyngeal carriage studies of Haemophilus influenzae type b (Hib)
      and the rapid drop in Hib invasive disease in countries with widespread Hib
      conjugate vaccine immunization programmes for infants have indicated there may be
      significant indirect effects (herd immunity) associated with these vaccines. Our
      goal was to quantify the magnitude of these effects in an American Indian
      population during its early years of Hib immunization. METHODS: In a synthetic
      case-cohort study, we combined data from an efficacy trial, an immunization
      uptake records survey, and ongoing surveillance for Hib disease on the Navajo
      Nation from 1988 to 1992. Decline in the incidence of invasive Hib disease among
      children <2 years old was estimated via proportional hazards survival models as a
      function of individual immunization status and the proportion of immunized
      children in a community. RESULTS: The predominant vaccine during the study period
      was Hib-OMPC (92% of immunizations). The effectiveness of receipt of at least one
      dose was 97.2%. Compared to communities with 0-20% coverage with at least one
      dose, residence in communities with 20-40% and 40-60% coverage was associated
      with risk reductions of 56.5% and 73.2%, respectively. CONCLUSIONS: The results
      indicate substantial indirect effects of Hib-OMPC immunization may occur even at
      relatively low levels of immunization coverage. Countries that implement Hib
      immunization programmes may receive greater benefits at the community level than
      those due to the direct protection conferred to the individual through
      vaccination.

PMID- 10922356
TI  - Vaccine-associated paralytic poliomyelitis: a retrospective cohort study of acute
      flaccid paralyses in Brazil.
AB  - BACKGROUND: At the present time, in Brazil and other countries in the Americas,
      the only cases of paralytic poliomyelitis due to poliovirus are caused by vaccine
      strains. The recognition of possible determinants of vaccine-associated paralytic
      poliomyelitis (VAPP) by public health surveillance and immunization programmes is
      relevant to inform the debate on criteria for case definition and vaccination
      strategies. METHODS: A retrospective cohort study based on the cases of acute
      flaccid paralysis (AFP) reported to the Ministry of Health (MoH) was designed,
      with the objective of studying cases of VAPP in Brazil between 1989 and 1995.
      Clinical, laboratory and epidemiological data from 3656 acute flaccid paralysis
      (AFP) cases, 30 of them diagnosed as VAPP, were analysed. RESULTS: An 8.88 risk
      ratio of VAPP (95% CI : 4.37-18.03) was found when comparing individuals who
      received oral poliovirus vaccine (OPV) between 4 and 40 days before the onset of
      paralysis and individuals who did not receive the vaccine within this period. A
      risk of 1 case/2.39 million first doses and 1 case/13.03 million OPV doses
      administered was estimated for the general population. CONCLUSIONS: Cases of AFP
      who received OPV between 4 and 40 days before the onset of paralysis and had
      fever, a prodrome of gastrointestinal symptoms, history of first dose of OPV,
      isolation of vaccine poliovirus type 2, and young age deserve careful
      investigation, since they are at increased risk for the condition studied.

PMID- 10922358
TI  - Questionnaire standards in epidemiology.

PMID- 10922357
TI  - Geographical patterns of cholera in Mexico, 1991-1996.
AB  - BACKGROUND: The seventh cholera pandemic has been ongoing in Mexico since 1991
      and threatens to become endemic. This paper aims to determine the geographical
      pattern of cholera in Mexico to define areas at high risk of endemic cholera.
      METHODS: Ecologic research was conducted based upon the cartography of disease
      incidence. The 32 Mexican states were grouped into five strata according to the
      value of the 1991-1996 cumulative incidence rate of cholera. Rate ratios were
      computed for strata of states classified by geographical situation, urbanization,
      and poverty level. RESULTS: Cholera incidence was 2.47 times higher in coastal
      states than in the interior (95% CI : 2.42-2.52). The disease was negatively
      associated with urbanization. Incidence in the least urbanized stratum was four
      times as high as in the most urban stratum (95% CI : 3.9-4.12). The poorest
      stratum showed the most remarkable incidence, i.e. 5.9 times higher than the rate
      in the least poor stratum (95% CI : 5.73-6.04). CONCLUSIONS: This ecologic
      research suggests that high poverty level, low urbanization, and southern
      location are the most important predictors of endemic cholera in Mexican states.
      It is hypothesized that the natural environment of the coastal plains in southern
      states may also play a significant role in cholera incidence. Poor communities
      residing in the southern, predominantly rural, coastal states should be
      prioritized when it comes to investing in safe water supply facilities, adequate
      excreta disposal systems and cholera surveillance.

PMID- 10922359
TI  - Expression of antisense to integrin subunit beta 3 inhibits microvascular
      endothelial cell capillary tube formation in fibrin.
AB  - alpha(v)beta(3) antagonists are potent angiogenesis inhibitors, and several
      different classes of inhibitors have been developed, including monoclonal
      antibodies, synthetic peptides, and small organic molecules. However, each class
      of inhibitor works by the same principal, by blocking the binding of ligands to
      alpha(v)beta(3). In an effort to develop an alpha(v)beta(3) inhibitor that down
      regulates the actual level of alpha(v)beta(3), we developed an antisense strategy
      to inhibit alpha(v)beta(3) expression in vitro. beta(3) antisense expressed in
      endothelial cells specifically down-regulated alpha(v)beta(3) and inhibited
      capillary tube formation, with the extent of down-regulation correlating with the
      extent of tube formation inhibition. This inhibition was matrix-specific, since
      tube formation was not inhibited in Matrigel. These findings support the notion
      that alpha(v)beta(3) is required for an essential step of angiogenesis in fibrin,
      namely capillary tube formation. These results suggest that pseudogenetic
      inhibition of beta(3) integrins using antisense techniques may ultimately provide
      a therapeutic means to inhibit angiogenesis in vivo.

PMID- 10922360
TI  - Cytochrome P450 CYP79B2 from Arabidopsis catalyzes the conversion of tryptophan
      to indole-3-acetaldoxime, a precursor of indole glucosinolates and indole-3
      acetic acid.
AB  - Glucosinolates are natural plant products known as flavor compounds, cancer
      preventing agents, and biopesticides. We report cloning and characterization of
      the cytochrome P450 CYP79B2 from Arabidopsis. Heterologous expression of CYP79B2
      in Escherichia coli shows that CYP79B2 catalyzes the conversion of tryptophan to
      indole-3-acetaldoxime. Recombinant CYP79B2 has a K(m) of 21 microm and a V(max)
      of 7.78 nmol/h/ml culture. Inhibitor studies show that CYP79B2 is different from
      a previously described enzyme activity that converts tryptophan to indole-3
      acetaldoxime (Ludwig-Muller, J. , and Hilgenberg, W. (1990) Phytochemistry, 29,
      1397-1400). CYP79B2 is wound-inducible and expressed in leaves, stem, flowers,
      and roots, with the highest expression in roots. Arabidopsis overexpressing
      CYP79B2 has increased levels of indole glucosinolates, which strongly indicates
      that CYP79B2 is involved in indole glucosinolate biosynthesis. Our data show that
      oxime production by CYP79s is not restricted to those amino acids that are
      precursors for cyanogenic glucosides. Our data are consistent with the hypothesis
      that indole glucosinolates have evolved from cyanogenesis. Indole-3-acetaldoxime
      is a precursor of the plant hormone indole-3-acetic acid, which suggests that
      CYP79B2 might function in biosynthesis of indole-3-acetic acid. Identification of
      CYP79B2 provides an important tool for modification of the indole glucosinolate
      content to improve nutritional value and pest resistance.

PMID- 10922361
TI  - Polyphosphate binding and chain length recognition of Escherichia coli
      exopolyphosphatase.
AB  - Exopolyphosphatase of Escherichia coli (PPX) is a highly processive enzyme
      demonstrating the ability to recognize polyphosphates of specific lengths. The
      mechanisms responsible for the processivity and polymer length recognition of the
      enzyme were investigated in relation to the manner in which polyphosphate is
      bound to the enzyme. Multiple polyphosphate binding sites were identified on
      distant portions of the enzyme and were determined to be responsible for the
      polymer length recognition of the enzyme. In addition, two independently folded
      domains were identified. The N-terminal domain contained a quasi-processive
      polyphosphatase active site belonging to the sugar kinase/actin/hsp70
      superfamily. The C-terminal domain contained a single polyphosphate binding site
      and was responsible for nearly all of the PPX affinity for polyphosphate. This
      domain was also found to confer a highly processive mode of action to PPX.
      Collectively, these results were used to describe the interaction of
      polyphosphate with PPX.

PMID- 10922362
TI  - Herp, a new ubiquitin-like membrane protein induced by endoplasmic reticulum
      stress.
AB  - Hyperhomocysteinemia, a risk factor for vascular disease, injures endothelial
      cells through undefined mechanisms. We previously identified several homocysteine
      responsive genes in cultured human vascular endothelial cells, including the
      endoplasmic reticulum (ER)-resident molecular chaperone GRP78/BiP. Here, we
      demonstrate that homocysteine induces the ER stress response and leads to the
      expression of a novel protein, Herp, containing a ubiquitin-like domain at the N
      terminus. mRNA expression of Herp was strongly up-regulated by inducers of ER
      stress, including mercaptoethanol, tunicamycin, A23187, and thapsigargin. The ER
      stress-dependent induction of Herp was also observed at the protein level.
      Immunochemical analyses using Herp-specific antibodies indicated that Herp is a
      54-kDa, membrane-associated ER protein. Herp is the first integral membrane
      protein regulated by the ER stress response pathway. Both the N and C termini
      face the cytoplasmic side of the ER; this membrane topology makes it unlikely
      that Herp acts as a molecular chaperone for proteins in the ER, in contrast to
      GRP78 and other ER stress-responsive proteins. Herp may, therefore, play an
      unknown role in the cellular survival response to stress.

PMID- 10922363
TI  - Molecular identification of cytosolic prostaglandin E2 synthase that is
      functionally coupled with cyclooxygenase-1 in immediate prostaglandin E2
      biosynthesis.
AB  - Here we report the molecular identification of cytosolic glutathione (GSH)
      dependent prostaglandin (PG) E(2) synthase (cPGES), a terminal enzyme of the
      cyclooxygenase (COX)-1-mediated PGE(2) biosynthetic pathway. GSH-dependent PGES
      activity in the cytosol of rat brains, but not of other tissues, increased 3-fold
      after lipopolysaccharide (LPS) challenge. Peptide microsequencing of purified
      enzyme revealed that it was identical to p23, which is reportedly the weakly
      bound component of the steroid hormone receptor/hsp90 complex. Recombinant p23
      expressed in Escherichia coli and 293 cells exhibited all the features of PGES
      activity detected in rat brain cytosol. A tyrosine residue near the N terminus
      (Tyr(9)), which is known to be critical for the activity of cytosolic GSH S
      transferases, was essential for PGES activity. The expression of cPGES/p23 was
      constitutive and was unaltered by proinflammatory stimuli in various cells and
      tissues, except that it was increased significantly in rat brain after LPS
      treatment. cPGES/p23 was functionally linked with COX-1 in marked preference to
      COX-2 to produce PGE(2) from exogenous and endogenous arachidonic acid, the
      latter being supplied by cytosolic phospholipase A(2) in the immediate response.
      Thus, functional coupling between COX-1 and cPGES/p23 may contribute to
      production of the PGE(2) that plays a role in maintenance of tissue homeostasis.

PMID- 10922364
TI  - Loss of either of the two heme-binding cysteines from a class I c-type cytochrome
      has a surprisingly small effect on physicochemical properties.
AB  - Almost without exception, c-type cytochromes have heme covalently attached via
      two thioether linkages to the cysteine residues of a CXXCH motif. The reasons for
      the covalent attachment are not understood. Reported here is cytoplasmic
      expression in Escherichia coli of AXXCH and CXXAH variants of cytochrome c(552)
      from Hydrogenobacter thermophilus; remarkably, the single thioether bond proteins
      have, apart from an altered visible absorption spectrum, almost identical
      properties, including thermal stability and reduction potential, to the wild type
      CXXCH protein. In combination with previous work showing that an AXXAH variant of
      cytochrome c(552) is much less stable than the CXXCH form, it can be concluded
      that covalent attachment of heme via either of thioether bonds is sufficient to
      confer considerable stability and that these bonds contribute little to the
      setting of the reduction potential. The absence of AXXCH or CXXAH heme-binding
      motifs from bacterial cytochromes c may relate to the coexistence of the assembly
      pathway with that for formation of disulfide bonds in the bacterial periplasm.

PMID- 10922365
TI  - Nitric-oxide dioxygenase activity and function of flavohemoglobins. sensitivity
      to nitric oxide and carbon monoxide inhibition.
AB  - Widely distributed flavohemoglobins (flavoHbs) function as NO dioxygenases and
      confer upon cells a resistance to NO toxicity. FlavoHbs from Saccharomyces
      cerevisiae, Alcaligenes eutrophus, and Escherichia coli share similar spectra,
      O(2), NO, and CO binding kinetics, and steady-state NO dioxygenation kinetics.
      Turnover numbers (V(max)) for S. cerevisiae, A. eutrophus, and E. coli flavoHbs
      are 112, 290, and 365 NO heme(-1) s(-1), respectively, at 37 degrees C with 200
      microm O(2). The K(M) values for NO are low and range from 0.1 to 0.25 microm.
      V(max)/K(M)(NO) ratios of 900-2900 microm(-1) s(-1) indicate an extremely
      efficient dioxygenation mechanism. Approximate K(M) values for O(2) range from 60
      to 90 microm. NO inhibits the dioxygenases at NO:O(2) ratios of > or =1:100 and
      makes true K(M)(O(2)) values difficult to determine. High and roughly equal
      second order rate constants for O(2) and NO association with the reduced flavoHbs
      (17-50 microm(-1) s(-1)) and small NO dissociation rate constants suggest that NO
      inhibits the dioxygenase reaction by forming inactive flavoHbNO complexes. Carbon
      monoxide also binds reduced flavoHbs with high affinity and competitively
      inhibits NO dioxygenases with respect to O(2) (K(I)(CO) = approximately 1
      microm). These results suggest that flavoHbs and related hemoglobins evolved as
      NO detoxifying components of nitrogen metabolism capable of discriminating O(2)
      from inhibitory NO and CO.

PMID- 10922366
TI  - Molecular characterization of lantibiotic-synthesizing enzyme EpiD reveals a
      function for bacterial Dfp proteins in coenzyme A biosynthesis.
AB  - The lantibiotic-synthesizing flavoprotein EpiD catalyzes the oxidative
      decarboxylation of peptidylcysteines to peptidyl-aminoenethiols. The sequence
      motif responsible for flavin coenzyme binding and enzyme activity is conserved in
      different proteins from all kingdoms of life. Dfp proteins of eubacteria and
      archaebacteria and salt tolerance proteins of yeasts and plants belong to this
      new family of flavoproteins. The enzymatic function of all these proteins was not
      known, but our experiments suggested that they catalyze a similar reaction like
      EpiD and/or may have similar substrates and are homododecameric flavoproteins. We
      demonstrate that the N-terminal domain of the Escherichia coli Dfp protein
      catalyzes the decarboxylation of (R)-4'-phospho-N-pantothenoylcysteine to 4'
      phosphopantetheine. This reaction is essential for coenzyme A biosynthesis.

PMID- 10922367
TI  - Cap-Poly(A) synergy in mammalian cell-free extracts. Investigation of the
      requirements for poly(A)-mediated stimulation of translation initiation.
AB  - The 5' cap and 3' poly(A) tail of eukaryotic mRNAs cooperate to stimulate
      synergistically translation initiation in vivo, a phenomenon observed to date in
      vitro only in translation systems containing endogenous competitor mRNAs. Here we
      describe nuclease-treated rabbit reticulocyte lysates and HeLa cell cytoplasmic
      extracts that reproduce cap-poly(A) synergy in the absence of such competitor
      RNAs. Extracts were rendered poly(A)-dependent by ultracentrifugation to
      partially deplete them of ribosomes and associated initiation factors. Under
      optimal conditions, values for synergy in reticulocyte lysates approached 10
      fold. By using this system, we investigated the molecular mechanism of poly(A)
      stimulation of translation. Maximal cap-poly(A) cooperativity required the
      integrity of the eukaryotic initiation factor 4G-poly(A)-binding protein (eIF4G
      PABP) interaction, suggesting that synergy results from mRNA circularization. In
      addition, polyadenylation stimulated uncapped cellular mRNA translation and that
      driven by the encephalomyocarditis virus internal ribosome entry segment (IRES).
      These effects of poly(A) were also sensitive to disruption of the eIF4G-PABP
      interaction, suggesting that 5'-3' end cross-talk is functionally conserved
      between classical mRNAs and an IRES-containing mRNA. Finally, we demonstrate that
      a rotaviral non-structural protein that evicts PABP from eIF4G is capable of
      provoking the shut-off of host cell translation seen during rotavirus infection.

PMID- 10922368
TI  - The amino-terminal domain of apolipoprotein B does not undergo retrograde
      translocation from the endoplasmic reticulum to the cytosol. Proteasomal
      degradation of nascent apolipoprotein B begins at the carboxyl terminus of the
      protein, while apolipoprotein B is still in its original translocon.
AB  - We studied the sequential topology of the NH(2) and COOH termini of apoB during
      translocation by expressing, in Chinese hamster ovary (CHO) and HepG2 cells, an
      apoB42 construct with c-Myc and hemagglutinin (HA) tags at 2 and 41% (relative to
      apoB100) of its amino acid sequence. We conducted similar studies using
      monoclonal antibodies against the NH(2) and COOH termini of apoB100 in HepG2
      cells. After radiolabeling, microsomes were immunoisolated from transfected CHO
      cells using anti-c-Myc or anti-HA antibodies. Throughout a 60-min chase in the
      presence of N-acetyl-leucyl-norleucinal, more than 90% of microsomes were
      isolated by anti-HA antibodies, whereas less than 10% were isolated by anti-c-Myc
      antibodies. Proteinase K digestion of total microsomes consistently generated two
      fragments ( approximately 70 and approximately 120 kDa) of apoB42 containing the
      NH(2) terminus throughout the chase; no fragments containing the COOH terminus
      were detected. Immunofluorescent studies of transfected CHO cells were consistent
      with results from the labeling studies. Essentially identical results were
      obtained from pulse-chase studies in both native and apoB42-transfected HepG2
      cells. The present studies support a model in which, in the absence of adequate
      core lipid synthesis, there is partial translocation of apoB leading to cytosolic
      exposure, ubiquitination, and proteasomal degradation directly from the original
      translocation channel.

PMID- 10922370
TI  - The Saccharomyces cerevisiae PCD1 gene encodes a peroxisomal nudix hydrolase
      active toward coenzyme A and its derivatives.
AB  - The PCD1 nudix hydrolase gene of Saccharomyces cerevisiae has been cloned and the
      Pcd1p protein characterized as a diphosphatase (pyrophosphatase) with specificity
      for coenzyme A and CoA derivatives. Oxidized CoA disulfide is preferred over CoA
      as a substrate with K(m) and k(cat) values of 24 micrometer and 5.0 s(-1),
      respectively, compared with values for CoA of 280 micrometer and 4.6 s(-1)
      respectively. The products of CoA hydrolysis were 3'-phosphoadenosine 5'
      monophosphate and 4'-phosphopantetheine. F(-) ions inhibited the activity with an
      IC(50) of 22 micrometer. The sequence of Pcd1p contains a potential PTS2
      peroxisomal targeting signal. When fused to the N terminus of yeast-enhanced
      green fluorescent protein, Pcd1p was shown to locate to peroxisomes by confocal
      microscopy. It was also shown to co-localize with peroxisomal thiolase by
      immunofluorescence microscopy. N-terminal sequence analysis of the expressed
      protein revealed the loss of 7 or 8 amino acids, suggesting processing of the
      proposed PTS2 signal after import. The function of Pcd1p may be to remove
      potentially toxic oxidized CoA disulfide from peroxisomes in order to maintain
      the capacity for beta-oxidation of fatty acids.

PMID- 10922369
TI  - Flagellin from an incompatible strain of Pseudomonas avenae induces a resistance
      response in cultured rice cells.
AB  - The host range of Pseudomonas avenae is wide among monocotyledonous plants, but
      individual strains can infect only one or a few host species. The resistance
      response of rice cells to pathogens has been previously shown to be induced by a
      rice-incompatible strain, N1141, but not by a rice-compatible strain, H8301. To
      clarify the molecular mechanism of the host specificity in P. avenae, a strain
      specific antibody that was raised against N1141 cells and then absorbed with
      H8301 cells was prepared. When a cell extract of strain N1141 was separated by
      SDS-polyacrylamide gel electrophoresis and immunostained with the N1141 strain
      specific antibody, only a flagellin protein was detected. Purified N1141
      flagellin induced the hypersensitive cell death in cultured rice cells within 6 h
      of treatment, whereas the H8301 flagellin did not. The hypersensitive cell death
      could be blocked by pretreatment with anti-N1141 flagellin antibody. Furthermore,
      a flagellin-deficient N1141 strain lost not only the induction ability of
      hypersensitive cell death but also the expression ability of the EL2 gene, which
      is thought to be one of the defense-related genes. These results demonstrated
      that the resistance response in cultured rice cells is induced by the flagellin
      existing in the incompatible strain of P. avenae but not in the flagellin of the
      compatible strain.

PMID- 10922371
TI  - Time-resolved infrared spectroscopy reveals a stable ferric heme-NO intermediate
      in the reaction of Paracoccus pantotrophus cytochrome cd1 nitrite reductase with
      nitrite.
AB  - Cytochrome cd(1) is a respiratory enzyme that catalyzes the physiological one
      electron reduction of nitrite to nitric oxide. The enzyme is a dimer, each
      monomer containing one c-type cytochrome center and one active site d(1) heme. We
      present stopped-flow Fourier transform infrared data showing the formation of a
      stable ferric heme d(1)-NO complex (formally d(1)Fe(II)-NO(+)) as a product of
      the reaction between fully reduced Paracoccus pantotrophus cytochrome cd(1) and
      nitrite, in the absence of excess reductant. The Fe-(14)NO nu(NO) stretching mode
      is observed at 1913 cm(-1) with the corresponding Fe-(15)NO band at 1876 cm(-1).
      This d(1) heme-NO complex is still readily observed after 15 min. EPR and visible
      absorption spectroscopic data show that within 4 ms of the initiation of the
      reaction, nitrite is reduced at the d(1) heme, and a cFe(III) d(1)Fe(II)-NO
      complex is formed. Over the next 100 ms there is an electron redistribution
      within the enzyme to give a mixed species, 55% cFe(III) d(1)Fe(II)-NO and 45%
      cFe(II) d(1)Fe(II)-NO(+). No kinetically competent release of NO could be
      detected, indicating that at least one additional factor is required for product
      release by the enzyme. Implications for the mechanism of P. pantotrophus
      cytochrome cd(1) are discussed.

PMID- 10922372
TI  - Vanadate induces p53 transactivation through hydrogen peroxide and causes
      apoptosis.
AB  - Vanadium is a metal widely distributed in the environment. Although vanadate
      containing compounds exert potent toxic effects on a wide variety of biological
      systems, the mechanisms controlling vanadate-induced adverse effects remain to be
      elucidated. The present study investigated the vanadate-induced p53 activation
      and involvement of reactive oxygen species (ROS) in p53 activation as well as the
      role of p53 in apoptosis induction by vanadate. Exposure of mouse epidermal JB6
      cells to vanadate led to transactivation of p53 activity in a time- and dose
      dependent manner. It also caused mitochondrial damage, apoptosis, and generated
      ROS. Scavenging of vanadate-induced H(2)O(2) by N-acetyl-l-cysteine (a general
      antioxidant) or catalase (a specific H(2)O(2) inhibitor), or the chelation of
      vanadate by deferoxamine, resulted in inhibition of p53 activation and cell
      mitochondrial damage. In contract, an increase in H(2)O(2) generation in response
      to superoxide dismutase or NADPH enhanced these effects caused by vanadate.
      Furthermore, vanadate-induced apoptosis occurred in cells expressing wild-type
      p53 (p53+/+) but was very weak in p53-deficient (p53-/-) cells. These results
      demonstrate that vanadate induces p53 activation mainly through H(2)O(2)
      generation, and this activation is required for vanadate-induced apoptosis.

PMID- 10922373
TI  - Evolution of the adhE gene product of Escherichia coli from a functional
      reductase to a dehydrogenase. Genetic and biochemical studies of the mutant
      proteins.
AB  - The multifunctional AdhE protein of Escherichia coli (encoded by the adhE gene)
      physiologically catalyzes the sequential reduction of acetyl-CoA to acetaldehyde
      and then to ethanol under fermentative conditions. The NH(2)-terminal region of
      the AdhE protein is highly homologous to aldehyde:NAD(+) oxidoreductases, whereas
      the COOH-terminal region is homologous to a family of Fe(2+)-dependent
      ethanol:NAD(+) oxidoreductases. This fusion protein also functions as a pyruvate
      formate lyase deactivase. E. coli cannot grow aerobically on ethanol as the sole
      carbon and energy source because of inadequate rate of adhE transcription and the
      vulnerability of the AdhE protein to metal-catalyzed oxidation. In this study, we
      characterized 16 independent two-step mutants with acquired and improved aerobic
      growth ability on ethanol. The AdhE proteins in these mutants catalyzed the
      sequential oxidation of ethanol to acetaldehyde and to acetyl-CoA. All first
      stage mutants grew on ethanol with a doubling time of about 240 min. Sequence
      analysis of a randomly chosen mutant revealed an Ala-267 --> Thr substitution in
      the acetaldehyde:NAD(+) oxidoreductase domain of AdhE. All second stage mutants
      grew on ethanol with a doubling time of about 90 min, and all of them produced an
      AdhE(A267T/E568K). Purified AdhE(A267T) and AdhE(A267T/E568K) showed highly
      elevated acetaldehyde dehydrogenase activities. It therefore appears that when
      AdhE catalyzes the two sequential reactions in the counter-physiological
      direction, acetaldehyde dehydrogenation is the rate-limiting step. Both mutant
      proteins were more thermosensitive than the wild-type protein, but
      AdhE(A267T/E568K) was more thermal stable than AdhE(A267T). Since both mutant
      enzymes exhibited similar kinetic properties, the second mutation probably
      conferred an increased growth rate on ethanol by stabilizing AdhE(A267T).

PMID- 10922374
TI  - KT5823 inhibits cGMP-dependent protein kinase activity in vitro but not in intact
      human platelets and rat mesangial cells.
AB  - Many signal transduction pathways are mediated by the second messengers cGMP and
      cAMP, cGMP- and cAMP-dependent protein kinases (cGK and PKA), phosphodiesterases,
      and ion channels. To distinguish among the different cGMP effectors, inhibitors
      of cGK and PKA have been developed including the K-252 compound KT5823 and the
      isoquinolinesulfonamide H89. KT5823, an in vitro inhibitor of cGK, has also been
      used in numerous studies with intact cells to implicate or rule out the
      involvement of this protein kinase in a given cellular response. However, the
      efficacy and specificity of KT5823 as cGK inhibitor in intact cells or tissues
      have never been demonstrated. Here, we analyzed the effects of both KT5823 and
      H89 on cyclic-nucleotide-mediated phosphorylation of vasodilator-stimulated
      phosphoprotein (VASP) in intact human platelets and rat mesangial cells. These
      two cell types both express high levels of cGK. KT5823 inhibited purified cGK.
      However, with both intact human platelets and rat mesangial cells, KT5823 failed
      to inhibit cGK-mediated serine 157 and serine 239 phosphorylation of VASP induced
      by nitric oxide, atrial natriuretic peptide, or the membrane-permeant cGMP
      analog, 8-pCPT-cGMP. KT5823 enhanced 8-pCPT-cGMP-stimulated VASP phosphorylation
      in platelets and did not inhibit forskolin-stimulated VASP phosphorylation in
      either platelets or mesangial cells. In contrast H89, an inhibitor of both PKA
      and cGK, clearly inhibited 8-pCPT-cGMP and forskolin-stimulated VASP
      phosphorylation in the two cell types. The data indicate that KT5823 inhibits
      purified cGK but does not affect a cGK-mediated response in the two different
      cell types expressing cGK I. These observations indicate that data that interpret
      the effects of KT5823 in intact cells as the major or only criteria supporting
      the involvement of cGK clearly need to be reconsidered.

PMID- 10922375
TI  - Creation of a stress-activated p90 ribosomal S6 kinase. The carboxyl-terminal
      tail of the MAPK-activated protein kinases dictates the signal transduction
      pathway in which they function.
AB  - Mitogen-activated protein kinase-activated protein kinases (MAPKAPKs) lie
      immediately downstream of the mitogen-activated protein kinases (MAPKs),
      extracellular signal-regulated kinase (ERK), and p38 MAPK. Although the family of
      MAPKAPKs shares sequence similarity, it demonstrates selectivity for the upstream
      activator. Here we demonstrate that each of the ERK- and p38 MAPK-regulated
      MAPKAPKs contains a MAPK docking site positioned distally to the residue(s)
      phosphorylated by MAPKs. The isolated MAPK docking sites show specificity for the
      upstream activator similar to that reported for the full-length proteins.
      Moreover, replacement of the ERK docking site of p90 ribosomal S6 kinase with the
      p38 MAPK docking site of MAPKAPK2 converts p90 ribosomal S6 kinase into a stress
      activated kinase in vivo. It is apparent that mechanisms controlling events
      downstream of the proline-directed MAPKs involve specific MAPK docking sites
      within the carboxyl termini of the MAPKAPKs that determine the cascade in which
      the MAPKAPK functions.

PMID- 10922376
TI  - Identification of the copper regulon in Saccharomyces cerevisiae by DNA
      microarrays.
AB  - In Saccharomyces cerevisiae, copper ions regulate gene expression through the two
      transcriptional activators, Ace1 and Mac1. Ace1 mediates copper-induced gene
      expression in cells exposed to stressful levels of copper salts, whereas Mac1
      activates a subset of genes under copper-deficient conditions. DNA microarray
      hybridization experiments revealed a limited set of yeast genes differentially
      expressed under growth conditions of excess copper or copper deficiency. Mac1
      activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1,
      FRE7, YFR055w, and YJL217w. Two of the last three newly identified Mac1 target
      genes have no known function; the third, YFR055w, is homologous to cystathionine
      gamma-lyase encoded by CYS3. Several genes that are differentially expressed in
      cells containing a constitutively active Mac1, designated Mac1(up1), are not
      direct targets of Mac1. Induction or repression of these genes is likely a
      secondary effect of cells because of constitutive Mac1 activity. Elevated copper
      levels induced the expression of the metallothioneins CUP1 and CRS5 and two
      genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1
      expression arises from an indirect copper effect on cellular iron pools.

PMID- 10922377
TI  - The mixed lineage kinase DLK is oligomerized by tissue transglutaminase during
      apoptosis.
AB  - Current evidence suggests that the mixed lineage kinase family member dual
      leucine zipper-bearing kinase (DLK) might play a significant role in the
      regulation of cell growth and differentiation, particularly during the process of
      tissue remodeling. To further explore this working model, we have investigated
      the regulation of host and recombinant DLK in NIH3T3 and COS-1 cells undergoing
      apoptosis. Using calphostin C, a potent and selective inhibitor of protein kinase
      C and a recognized apoptosis inducer for various cell types, we demonstrate, by
      immunoblot analysis, that DLK protein levels are rapidly and dramatically down
      regulated during the early phases of apoptosis. Down-regulation in calphostin C
      treated cells was also accompanied by the appearance of SDS- and mercaptoethanol
      resistant high molecular weight DLK immunoreactive oligomers. Experiments aimed
      at elucidating the mechanism(s) underlying DLK oligomerization revealed that the
      tissue transglutaminase (tTG) inhibitor monodansylcadaverine antagonized the
      effects of calphostin C almost completely, thereby suggesting the involvement of
      a tTG-catalyzed reaction as the root cause of DLK down-regulation and
      accumulation as high molecular weight species. In support of this notion, we also
      show that DLK can serve as a substrate for tTG-dependent cross-linking in vitro
      and that this covalent post-translational modification leads to the functional
      inactivation of DLK. Taken together, these observations suggest that
      transglutamination and oligomerization may constitute a relevant physiological
      mechanism for the regulation of DLK activity.

PMID- 10922378
TI  - Tissue factor pathway inhibitor binds to platelet thrombospondin-1.
AB  - Tissue factor pathway inhibitor (TFPI) is a Kunitz-type serine proteinase
      inhibitor that down-regulates tissue factor-initiated blood coagulation. The most
      biologically active pool of TFPI is associated with the vascular endothelium,
      however, the biochemical mechanisms responsible for its cellular binding are not
      entirely defined. Proposed cellular binding sites for TFPI include nonspecific
      association with cell surface glycosaminoglycans and binding to glycosyl
      phosphatidylinositol-anchored proteins. Here, we report that TFPI binds
      specifically and saturably to thrombospondin-1 (TSP-1) purified from platelet
      alpha-granules with an apparent K(D) of approximately 7.5 nm. Binding is
      inhibited by polyclonal antibodies against TFPI and partially inhibited by the B
      7 monoclonal anti-TSP-1 antibody. TFPI bound to immobilized TSP-1 remains an
      active proteinase inhibitor. Additionally, in solution phase assays measuring
      TFPI inhibition of factor VIIa/tissue factor catalytic activity, the rate of
      factor Xa generation was decreased 55% in the presence of TSP-1 compared with
      TFPI alone. Binding experiments done in the presence of heparin and with altered
      forms of TFPI suggest that the basic C-terminal region of TFPI is required for
      TSP-1 binding. The data provide a mechanism for the recruitment and localization
      of TFPI to extravascular surfaces within a bleeding wound, where it can
      efficiently down-regulate the procoagulant activity of tissue factor and allow
      subsequent aspects of platelet-mediated healing to proceed.

PMID- 10922379
TI  - A novel murine beta -defensin expressed in tongue, esophagus, and trachea.
AB  - beta-Defensins are broad spectrum antimicrobial peptides expressed at epithelial
      surfaces. Two human beta-defensins, HBD-1 and HBD-2, have been identified. In the
      lung, HBD-2 is an inducible product of airway epithelia and may play a role in
      innate mucosal defenses. We recently characterized rat homologs (RBD-1, RBD-2) of
      the human genes and used these sequences to identify novel mouse genes. Mouse
      beta-defensin-4 (MBD-4) was amplified from lung cDNA using polymerase chain
      reaction primers designed from conserved sequences of RBD-2 and HBD-2. A full
      length cDNA was cloned which encodes a putative peptide with the sequence
      MRIHYLLFTFLLVLLSPLAAFTQIINNPITCMTNGAICWGPCPTAFRQIGNCGHFKVRCCKIR. The peptide
      shares approximately 40% identity with HBD-2. MBD-4 mRNA was expressed in the
      esophagus, tongue, and trachea but not in any of 20 other tissues surveyed.
      Cloning of the genomic sequence of MBD-4 revealed two nearly (>99%) identical
      sequences encoding MBD-4 and the presence of numerous additional highly similar
      genomic sequences. Radiation hybrid mapping localized this gene to a region of
      chromosome 8 near several other defensins, MBD-2, MBD-3, and alpha-defensins
      (cryptdins)-3 and -17, consistent with a gene cluster. Our genomic cloning and
      mapping data suggest that there is a large beta-defensin gene family in mice.
      Identification of murine beta-defensins provides an opportunity to understand
      further the role of these peptides in host defense through animal model studies
      and the generation of beta-defensin-deficient animals by gene targeting.

PMID- 10922381
TI  - Ten years of presymptomatic testing for Huntington's disease: the experience of
      the UK Huntington's Disease Prediction Consortium.
AB  - Data on all presymptomatic genetic tests for Huntington's disease (HD) in the UK
      have been collected over the 10 year period since testing became available as a
      service. A total of 2937 completed tests have been performed up to the end of
      1997, 2502 based on specific mutation testing, feasible since late 1993.A total
      of 93.1% of these were at 50% prior risk, with a significant excess of females
      (58.3%); 41.4% of results were abnormal or high risk, including 29.4% in subjects
      aged 60 or over. The trend in test numbers has currently levelled out at around
      500 per year. Almost all presymptomatic tests are carried out in National Health
      Service genetics centres, with a defined genetic counselling protocol and with
      availability now in all regions of the UK. The introduction and establishment of
      HD presymptomatic testing shows that this form of predictive medicine for
      Mendelian disorders can be successfully incorporated into National Health Service
      structures. The comprehensive collection of simple data allows trends in demand
      and outcomes to be monitored and has also been the foundation for more detailed
      specific studies. A comparable approach to data collection in other genetic
      disorders will be important as presymptomatic testing becomes more generally
      feasible.

PMID- 10922380
TI  - Autosomal dominant sacral agenesis: Currarino syndrome.
AB  - Autosomal dominant sacral agenesis is characterised by a partial agenesis of the
      sacrum typically involving sacral vertebrae S2-S5 only. Associated features
      include anorectal malformation, a presacral mass, and urogenital malformation.
      Together, these features have been defined as the Currarino syndrome. Recently,
      HLXB9 has been identified as the major causative gene in Currarino syndrome
      allowing identification of asymptomatic heterozygotes. In this review, we have
      performed an analysis of medical publications, and our own additional cases, to
      identify the range of malformations and complications that occur. We have also
      estimated risks of malformation in heterozygotes by using Weinburg's proband
      method on families personally known to us in order to provide accurate genetic
      counselling information.

PMID- 10922382
TI  - RET genotypes comprising specific haplotypes of polymorphic variants predispose
      to isolated Hirschsprung disease.
AB  - BACKGROUND: Hirschsprung disease (HSCR), which may be sporadic or familial,
      occurs in 1:5000 live births and presents with functional intestinal obstruction
      secondary to aganglionosis of the hindgut. Germline mutations of the RET proto
      oncogene are believed to account for up to 50% of familial cases and up to 30% of
      isolated cases in most series. However, these series are highly selected for the
      most obvious and severe cases and large familial aggregations. Population based
      studies indicate that germline RET mutations account for no more than 3% of
      isolated HSCR cases. Recently, we and others have noted that specific polymorphic
      sequence variants, notably A45A (exon 2), are over-represented in isolated HSCR.
      PURPOSE: In order to determine if it is the variant per se, a combination
      thereof, or another locus in linkage disequilibrium which predisposes to HSCR, we
      looked for association of RET haplotype(s) and disease in HSCR cases compared to
      region matched controls. METHODS: Seven loci across RET were typed and haplotypes
      formed for HSCR cases, their unaffected parents, and region matched controls.
      Haplotype and genotype frequencies and distributions were compared among these
      groups using the transmission disequilibrium test and standard case-control
      statistic. RESULTS: Twelve unique haplotypes, labelled A-L, were obtained. The
      distributions of haplotypes between cases and controls (chi(11)(2) =81.4,
      p<<0.0001) and between cases and non-transmitted parental haplotypes were
      significantly different (chi(2)(11)=53.1, p<0.0001). Genotypes comprising pairs
      of haplotypes were formed for cases and controls. There were 38 different
      genotypes among cases and controls combined. Inspection of the genotypes in these
      two groups showed that the genotype distribution between cases and controls was
      distinct (chi(37)(2)=93. 8, p<<0.0001). For example, BB, BC, BD, and CD, all of
      which contain at least one allele with the polymorphic A45A, are prominently
      represented among HSCR cases, together accounting for >35% of the case genotypes,
      yet these four genotypes were not represented among the population matched normal
      controls. Conversely, AA, AG, DD, GG, and GJ, none of which contains A45A, are
      commonly represented in the controls, together accounting for 43% of the control
      genotypes, and yet they are never seen among the HSCR cases. CONCLUSIONS: Our
      data suggest that genotypes comprising specific pairs of RET haplotypes are
      associated with predisposition to HSCR either in a simple autosomal recessive
      manner or in an additive, dose dependent fashion.

PMID- 10922383
TI  - Identification of four novel PMM2 mutations in congenital disorders of
      glycosylation (CDG) Ia French patients.
AB  - We screened 11 unrelated French patients with congenital disorders of
      glycosylation (CDG) Ia for PMM2 mutations. Twenty one missense mutations on the
      22 chromosomes (95%) including four novel mutations were identified: C9Y (G26A)
      in exon 1, L32R (TA95GC) in exon 2, and T226S (C677G) and C241S (G722C) in exon
      8. We studied the PMM activity of these four novel mutant proteins and of the
      R141H mutant protein in an E coli expression system. The T226S, C9Y, L32R, and
      C241S mutant proteins have decreased specific activity (23 to 41% of normal), are
      all more or less thermolabile, and R141H has no detectable activity. Our results
      indicate that the new mutations identified here are less severe than the inactive
      R141H mutant protein, conferring residual PMM activity compatible with life.

PMID- 10922384
TI  - Detailed mapping of a congenital heart disease gene in chromosome 3p25.
AB  - Distal deletion of chromosome 3p25-pter (3p- syndrome) produces a distinct
      clinical syndrome characterised by low birth weight, mental retardation,
      telecanthus, ptosis, and micrognathia. Congenital heart disease (CHD), typically
      atrioventricular septal defect (AVSD), occurs in about a third of patients. In
      total, approximately 25 cases of 3p- syndrome have been reported world wide. We
      previously analysed five cases and showed that (1) the 3p25-pter deletions were
      variable and (2) the presence of CHD correlated with the proximal extent of the
      deletion, mapping a CHD gene centromeric to D3S18. To define the molecular
      pathology of the 3p- syndrome further, we have now proceeded to analyse the
      deletion region in a total of 10 patients (five with CHD), using a combination of
      FISH analysis and polymorphic markers, for up to 21 loci from 3p25-p26. These
      additional investigations further supported the location of an AVSD locus within
      3p25 and refined its localisation. Thus, the critical region was reduced to an
      interval between D3S1263 and D3S3594. Candidate 3p25 CHD genes, such as PMCA2
      (ATP2B2), fibulin 2, TIMP4, and Sec13R, were shown to map outside the target
      interval. Additionally, the critical region for the phenotypic features of the 3p
      phenotype was mapped to D3S1317 to D3S17 (19-21 cM). These findings will
      accelerate the identification of the 3p25 CHD susceptibility locus and facilitate
      investigations of the role of this locus in non-syndromic AVSDs, which are a
      common form of familial and isolated CHD.

PMID- 10922385
TI  - The role of hypermethylation of the hMLH1 promoter region in HNPCC versus MSI+
      sporadic colorectal cancers.
AB  - INTRODUCTION: Hypermethylation of the promoter region of the hMLH1 gene is
      associated with absent expression of MLH1 protein in sporadic colorectal cancers
      with microsatellite instability (MSI+), and it has been proposed that methylation
      may be a mechanism of inactivation in Knudson's hypothesis. The incidence of
      hypermethylation of the hMLH1 promoter in hereditary non-polyposis colorectal
      cancer (HNPCC) versus MSI+ sporadic colorectal cancer was investigated and
      compared. METHODS: DNA was available from 10 HNPCC colorectal cancers (median age
      58 years, range 39-67) with germline mutations in hMLH1 and 10 MSI+ sporadic
      colorectal cancers (mean age 79 years, range 41-85). MSI was determined by
      amplification of BAT26 and TGF-beta RII. The methylation status of the hMLH1
      promoter was studied by the polymerase chain reaction (PCR) based HpaII
      restriction enzyme assay technique. Evidence of allelic loss at hMLH1 was
      searched for in the HNPCC colorectal cancers. RESULTS: All cases were confirmed
      to be MSI+. The promoter region of hMLH1 was hypermethylated in seven of 10 MSI+
      sporadic cancers versus 0 of 10 HNPCC cancers (p<0.002). Evidence of loss of
      heterozygosity at hMLH1 was observed in eight of the 10 HNPCC colorectal cancers.
      CONCLUSION: While mutations and allelic loss are responsible for the MSI+
      phenotype in HNPCC cancers, the majority of MSI+ sporadic cancers are
      hypermethylated in the promoter region of hMLH1. These data further support our
      argument that tumours from HNPCC patients, which almost always acquire a raised
      mutation rate, mostly follow a different pathway from MSI+ sporadic tumours.

PMID- 10922387
TI  - Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental
      retardation, and epilepsy.
AB  - We describe monozygotic male twins with an interstitial deletion of Xp22.3
      including the steroid sulphatase gene (STS). The twins had X linked ichthyosis, X
      linked mental retardation, and epilepsy. A locus for X linked mental retardation
      has been assigned to a region between STS and DXS31 spanning approximately 3 Mb.
      Recently the locus was further refined to an approximately 1 Mb region between
      DXS1060 and GS1. By PCR analysis of flanking STS gene markers in our patients we
      succeeded in narrowing down the locus to between DXS6837 and GS1.

PMID- 10922386
TI  - FISH deletion mapping defines a single location for the Y chromosome stature
      gene, GCY.
AB  - At least 1 in 1000 males lacks part of the long arm of the Y chromosome. This
      chromosomal aberration is often associated with short stature and infertility.
      Deletion mapping and genotype-phenotype analysis have previously defined two non
      overlapping critical regions for growth controlling gene(s), GCY(s), on the
      euchromatic portion of the Y chromosome long arm. These initial mapping
      assignments were based on the analysis of patients carrying a pure 46,XYq-
      karyotype as defined by classical cytogenetic karyotyping. Four genes have been
      assigned to the distal one of the two critical regions. To determine whether one
      or both of these two critical regions harbours GCY and whether one of the four
      genes assigned to the distal region is involved in determination of stature, nine
      adult patients with Yq chromosomal abnormalities were studied in detail. By PCR
      and FISH analysis, we showed that all patients with a previously defined pure
      46,XYq- karyotype are actually mosaics with cells containing an idic(Y) or
      ring(Y) chromosome in association with 45,X0 cells. This leads us to conclude
      that (1) FISH is an absolute prerequisite for the correct identification of Y
      chromosomal rearrangements and (2) only patients with interstitial Y deletions
      are reliable predictors for the physical location of stature gene(s) on Yq. Our
      molecular analyses of chromosomes from patients with interstitial Yq deletions
      finally establishes the proximal interval between markers DYZ3 and DYS11 as the
      only GCY critical interval. No functional gene has so far been identified in this
      region adjacent to the centromere.

PMID- 10922388
TI  - Twin sisters, monozygotic with the fragile X mutation, but with a different
      phenotype.
AB  - The absence of the fragile X mental retardation protein (FMRP) results in fragile
      X syndrome. All males with a full mutation in the FMR1 gene and an inactive FMR1
      gene are mentally retarded while 60% of the females with a full mutation are
      affected. Here we describe monozygotic twin sisters who both have a full mutation
      in their FMR1 gene, one of whom is normal while the other is affected. Using
      molecular and protein studies it was shown that owing to preferential X
      inactivation in the affected female a minority of the cells expressed the normal
      FMR1 gene, while in her sister most cells expressed the normal FMR1 gene. This
      shows that X inactivation took place in the female twins after separation of the
      embryos and that for a normal phenotype FMR1 expression is necessary in the
      majority of cells.

PMID- 10922390
TI  - Duplication of medial 15q confirmed by FISH.

PMID- 10922389
TI  - A survey of the current clinical facilities for the management of familial cancer
      in Europe. European Union BIOMED II Demonstration Project: Familial Breast
      Cancer: audit of a new development in medical practice in European centres.

PMID- 10922391
TI  - A child with bisatellited, dicentric chromosome 15 arising from a maternal
      paracentric inversion of chromosome 15q.

PMID- 10922392
TI  - A family with hereditary port wine stain.

PMID- 10922393
TI  - Absence of germline p16(INK4a) alterations in p53 wild type Li-Fraumeni syndrome
      families.

PMID- 10922394
TI  - Distal spinal muscular atrophy with vocal cord paralysis (dSMA-VII) is not linked
      to the MPD2 locus on chromosome 5q31.

PMID- 10922395
TI  - Fetal bowel hyperechogenicity may indicate mild atypical cystic fibrosis: a case
      associated with a complex CFTR allele.

PMID- 10922396
TI  - Distribution of CFTR gene mutations in cystic fibrosis patients from Estonia.

PMID- 10922397
TI  - Predicting breast cancer: the search for a model.

PMID- 10922398
TI  - Optimizing dendritic cell function by genetic modification.

PMID- 10922399
TI  - Mixed moniker: 'mini' marrow transplants fuel excitement, concern.

PMID- 10922400
TI  - A brief history of the brief history of low-dose transplants.

PMID- 10922401
TI  - Cutting copper curbs angiogenesis, studies show.

PMID- 10922402
TI  - Pharmacoeconomic analyses make way into oncology.

PMID- 10922403
TI  - Melanoma vaccine momentum spurs interest, investment.

PMID- 10922404
TI  - Stat bite: Lowest mortality from melanoma by U.S. state, 1970-1994.

PMID- 10922405
TI  - Standard imaging techniques may monitor angiogenesis.

PMID- 10922406
TI  - Histone deacetylase inhibitors: inducers of differentiation or apoptosis of
      transformed cells.
AB  - Histone deacetylase (HDAC) inhibitors have been shown to be potent inducers of
      growth arrest, differentiation, and/or apoptotic cell death of transformed cells
      in vitro and in vivo. One class of HDAC inhibitors, hydroxamic acid-based hybrid
      polar compounds (HPCs), induce differentiation at micromolar or lower
      concentrations. Studies (x-ray crystallographic) showed that the catalytic site
      of HDAC has a tubular structure with a zinc atom at its base and that these HDAC
      inhibitors, such as suberoylanilide hydroxamic acid and trichostatin A, fit into
      this structure with the hydroxamic moiety of the inhibitor binding to the zinc.
      HDAC inhibitors cause acetylated histones to accumulate in both tumor and normal
      tissues, and this accumulation can be used as a marker of the biologic activity
      of the HDAC inhibitors. Hydroxamic acid-based HPCs act selectively to inhibit
      tumor cell growth at levels that have little or no toxicity for normal cells.
      These compounds also act selectively on gene expression, altering the expression
      of only about 2% of the genes expressed in cultured tumor cells. In general,
      chromatin fractions enriched in actively transcribed genes are also enriched in
      highly acetylated core histones, whereas silent genes are associated with
      nucleosomes with a low level of acetylation. However, HDACs can also acetylate
      proteins other than histones in nucleosomes. The role that these other targets
      play in the induction of cell growth arrest, differentiation, and/or apoptotic
      cell death has not been determined. Our working hypothesis is that inhibition of
      HDAC activity leads to the modulation of expression of a specific set of genes
      that, in turn, result in growth arrest, differentiation, and/or apoptotic cell
      death. The hydroxamic acid-based HPCs are potentially effective agents for cancer
      therapy and, possibly, cancer chemoprevention.

PMID- 10922407
TI  - Short-term breast cancer prediction by random periareolar fine-needle aspiration
      cytology and the Gail risk model.
AB  - BACKGROUND: : Biomarkers are needed to refine short-term breast cancer risk
      estimates from epidemiologic models and to measure response to prevention
      interventions. The purpose of our study was to determine whether the cytologic
      appearance of epithelial cells obtained from breast random periareolar fine
      needle aspirates or molecular marker expression in these cells was associated
      with later breast cancer development. METHODS: : Four hundred eighty women who
      were eligible on the basis of a family history of breast cancer, prior
      precancerous biopsy, and/or prior invasive cancer were enrolled in a single
      institution, prospective trial. Their risk of breast cancer according to the Gail
      model was calculated, and random periareolar fine-needle aspiration was performed
      at study entry. Cells were characterized morphologically and analyzed for DNA
      aneuploidy by image analysis and for the expression of epidermal growth factor
      receptor, estrogen receptor, p53 protein, and HER2/NEU protein by
      immunocytochemistry. All statistical tests are two-sided. RESULTS: : At a median
      follow-up time of 45 months after initial aspiration, 20 women have developed
      breast cancer (invasive disease in 13 and ductal carcinoma in situ in seven).
      With the use of multiple logistic regression and Cox proportional hazards
      analysis, subsequent cancer was predicted by evidence of hyperplasia with atypia
      in the initial fine-needle aspirate and a 10-year Gail projected probability of
      developing breast cancer. Although expression of epidermal growth factor
      receptor, estrogen receptor, p53, and HER2/NEU was statistically significantly
      associated with hyperplasia with atypia, it did not predict the development of
      breast cancer in multivariable analysis. CONCLUSION: : Cytomorphology from breast
      random periareolar fine-needle aspirates can be used with the Gail risk model to
      identify a cohort of women at very high short-term risk for developing breast
      cancer. We recommend that cytomorphology be studied for use as a potential
      surrogate end point in prevention trials.

PMID- 10922408
TI  - Enhanced activation of T cells by dendritic cells engineered to hyperexpress a
      triad of costimulatory molecules.
AB  - BACKGROUND: Activation and proliferation of T cells are essential for a
      successful cellular immune response to an antigen. Antigen-presenting cells
      (APCs) activate T cells through a two-signal mechanism. The first signal is
      antigen specific and causes T cells to enter the cell cycle. The second signal
      involves a costimulatory molecule that interacts with a ligand on the T-cell
      surface and leads to T-cell cytokine production and their proliferation.
      Dendritic cells express several costimulatory molecules and are believed to be
      the most potent APCs. Two recombinant poxvirus vectors (replication-defective
      avipox [fowlpox; rF] and a replication-competent vaccinia [rV]) have been
      engineered to express a triad of costimulatory molecules (B7-1, intercellular
      adhesion molecule-1, and leukocyte function-associated antigen-3; designated
      TRICOM). This study was designed to determine if dendritic cells infected with
      these vectors would have an enhanced capacity to stimulate T-cell responses.
      METHODS: Murine dendritic cells (of both intermediate maturity and full maturity)
      were infected with rF-TRICOM or rV-TRICOM and were used in vitro to stimulate
      naive T cells with the use of a pharmacologic agent as signal 1, to stimulate T
      cells in allospecific mixed lymphocyte cultures, and to stimulate CD8(+) T cells
      specific for a peptide from the ovalbumin (OVA) protein. In addition, dendritic
      cells infected with TRICOM vectors were pulsed with OVA peptide and used to
      vaccinate mice to examine T-cell responses in vivo. All statistical tests were
      two-sided. RESULTS: Dendritic cells infected with either rF-TRICOM or rV-TRICOM
      were found to greatly enhance naive T-cell activation (P<.001), allogeneic
      responses of T cells (P<.001), and peptide-specific T-cell stimulation in vitro
      (P<.001). Peptide-pulsed dendritic cells infected with rF-TRICOM or rV-TRICOM
      induced cytotoxic T-lymphocyte activity in vivo to a markedly greater extent than
      peptide-pulsed dendritic cells (P =.001 in both). CONCLUSIONS: The ability of
      dendritic cells to activate both naive and effector T cells in vitro and in vivo
      can be enhanced with the use of poxvirus vectors that potentiate the
      hyperexpression of a triad of costimulatory molecules. Use of either rF-TRICOM or
      rV-TRICOM vectors significantly improved the efficacy of dendritic cells in
      priming specific immune responses. These studies have implications in vaccine
      strategies for both cancer and infectious diseases.

PMID- 10922409
TI  - Cancer surveillance series: non-Hodgkin's lymphoma incidence by histologic
      subtype in the United States from 1978 through 1995.
AB  - BACKGROUND: Clinical investigations have shown prognostic heterogeneity within
      the non-Hodgkin's lymphomas (NHLs) according to histology, but few descriptive
      studies have considered NHLs by subgroup. Our purpose is to assess the
      demographic patterns and any notable increases in population-based rates of
      different histologic subgroups of NHL. METHODS: Using data collected by the
      Surveillance, Epidemiology, and End Results Program of the National Cancer
      Institute, we calculated incidence rates for the major clinicopathologic
      categories of NHL by age, race, sex, geographic area, and time period. RESULTS:
      Among the 60 057 NHL cases diagnosed during the period from 1978 through 1995,
      total incidence (per 100 000 person-years) was 17.1 and 11.5 among white males
      and females, respectively, and 12.6 and 7.4 among black males and females,
      respectively. However, rates for follicular NHLs were two to three times greater
      among whites than among blacks, with little sex variation. Blacks demonstrated
      much higher incidence than whites for peripheral T-cell NHL, with the incidence
      rates higher in males than in females. For other NHL subgroups, the incidence
      rates for persons less than 60 years of age were generally higher among males
      than among females, with little racial difference; at older ages, the rates were
      higher among whites than among blacks, with little sex difference. High-grade NHL
      was the most rapidly rising subtype, particularly among males. Follicular NHL
      increased more rapidly in black males than in the other three race/sex groups.
      Overall, the broad categories of small lymphocytic, follicular, diffuse, high
      grade, and peripheral T-cell NHL emerged as distinct entities with specific age,
      sex, racial, temporal, and geographic variations in rates. CONCLUSIONS: Findings
      from our large, population-based study reveal differing demographic patterns and
      incidence trends according to histologic group. Future descriptive and analytic
      investigations should evaluate NHL risks according to subtype, as defined by
      histology and new classification criteria.

PMID- 10922413
TI  - Zink

PMID- 10922410
TI  - Detecting activation of ribosomal protein S6 kinase by complementary DNA and
      tissue microarray analysis.
AB  - BACKGROUND: Studies by comparative genomic hybridization (CGH) have shown that
      chromosomal region 17q23 is amplified in up to 20% of primary breast cancers. We
      used microarray analyses to measure the expression levels of genes in this region
      and to explore their prognostic importance. METHODS: A microarray that contained
      4209 complementary DNA (cDNA) clones was used to identify genes that are
      overexpressed in the MCF-7 breast cancer cell line as compared with normal
      mammary tissue. Fluorescence in situ hybridization was used to analyze the copy
      number of one overexpressed gene, ribosomal protein S6 kinase (S6K), and to
      localize it to the 17q23 region. Northern and western blot analyses were used to
      measure S6K gene and protein expression, and an enzymatic assay was used to
      measure S6K activity. Tumor tissue microarray analysis was used to study
      amplification of S6K and the HER-2 oncogene, another 17q-linked gene, and the
      relationship between amplification and prognosis was analyzed. The Kaplan-Meier
      method was used for data analysis, and the log-rank test was used for statistical
      analysis. All P values are two-sided. RESULTS: S6K was amplified and highly
      overexpressed in MCF-7 cells relative to normal mammary epithelium, and protein
      expression and enzyme activity were increased. S6K was amplified in 59 (8.8%) of
      668 primary breast tumors, and a statistically significant association between
      amplification and poor prognosis (P =.0021) was observed. Amplification of both
      S6K and HER-2 implied particularly poor survival (P =.0001). CONCLUSIONS: The
      combination of CGH information with cDNA and tissue microarray analyses can be
      used to identify amplified and overexpressed genes and to evaluate the clinical
      implications of such genes and genomic rearrangements. S6K is likely to be one of
      the genes at 17q23 that is amplified during oncogenesis and may adversely affect
      the prognosis of patients with this amplification.

PMID- 10922411
TI  - High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A
      mutation-positive melanoma families.
AB  - BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which
      encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene
      confer susceptibility to cutaneous malignant melanoma. We analyzed families with
      two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to
      elucidate the contribution of these gene defects to familial malignant melanoma
      and to the occurrence of other cancer types. METHODS: : The entire CDKN2A coding
      region and exon 2 of the CDK4 gene of an affected member of each of 52 families
      from southern Sweden with at least two cases of melanoma in first- or second
      degree relatives were screened for mutations by use of polymerase chain reaction
      single-strand conformation polymorphism analysis. Statistical tests were two
      sided. RESULTS: : CDKN2A mutations were found in 10 (19%) of the 52 families.
      Nine families carried an identical alteration consisting of the insertion of
      arginine at position 113 of p16(INK4a), and one carried a missense mutation, in
      which the valine at position 115 was replaced with a glycine. The 113insArg
      mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay.
      Six of the 113insArg families had at least one member with multiple primary
      melanomas; the 113insArg families also had a high frequency of other malignancies
      in particular, breast cancer (a total of eight cases compared with the expected
      2.1; P =.0014) and pancreatic cancer (a total of six cases compared with the
      expected 0.16; P<.0001). Families with breast cancer also had a propensity for
      multiple melanomas in females, suggesting that a sex-dependent factor may modify
      the phenotypic expression of CDKN2A alterations. CONCLUSIONS: : Our findings
      confirm that the majority of CDKN2A-associated melanoma families in Sweden are
      due to a single founder mutation. They also show that families with the CDKN2A
      113insArg mutation have an increased risk not only of multiple melanomas and
      pancreatic carcinoma but also of breast cancer.

PMID- 10922414
TI  - Let's leave the date out of the name of the standard population.

PMID- 10922415
TI  - Re: dietary folate consumption and breast cancer risk.

PMID- 10922416
TI  - RESPONSE: Let's leave the date out of the name of the standard population

PMID- 10922417
TI  - Re: randomized trial of high-dose chemotherapy and blood cell autografts for high
      risk primary breast carcinoma.

PMID- 10922418
TI  - EDITOR'S NOTE: re: randomized trial of high-dose chemotherapy and blood cell
      autografts for high-risk primary breast carcinoma

PMID- 10922419
TI  - RESPONSE: re: randomized trial of high-dose chemotherapy and blood cell
      autografts for high-risk primary breast carcinoma

PMID- 10922420
TI  - Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment
      of bleeding peptic ulcers.
AB  - BACKGROUND: After endoscopic treatment of bleeding peptic ulcers, bleeding recurs
      in 15 to 20 percent of patients. METHODS: We assessed whether the use of a high
      dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding
      after endoscopic treatment of bleeding peptic ulcers. Patients with actively
      bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an
      epinephrine injection followed by thermocoagulation. After hemostasis had been
      achieved, they were randomly assigned in a double-blind fashion to receive
      omeprazole (given as a bolus intravenous injection of 80 mg followed by an
      infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all
      patients were given 20 mg of omeprazole orally per day for eight weeks. The
      primary end point was recurrent bleeding within 30 days after endoscopy. RESULTS:
      We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in
      8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5
      percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval,
      1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three
      days, which made up the infusion period (5 in the omeprazole group and 24 in the
      placebo group, P<0.001). Three patients in the omeprazole group and nine in the
      placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the
      omeprazole group and 12 (10 percent) in the placebo group died within 30 days
      after endoscopy (P=0.13). CONCLUSIONS: After endoscopic treatment of bleeding
      peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk
      of recurrent bleeding.

PMID- 10922421
TI  - Pravastatin therapy and the risk of stroke.
AB  - BACKGROUND: Several epidemiologic studies have concluded that there is no
      relation between total cholesterol levels and the risk of stroke. In some studies
      that classified strokes according to cause, there was an association between
      increasing cholesterol levels and the risk of ischemic stroke and a possible
      association between low cholesterol levels and the risk of hemorrhagic stroke.
      Recent reviews of trials of 3-hydroxy-3-methylglutaryl-coenzyme A reductase
      inhibitors have suggested that these agents may reduce the risk of stroke.
      METHODS: In a double-blind trial (the Long-Term Intervention with Pravastatin in
      Ischaemic Disease study), we compared the effects of pravastatin on mortality due
      to coronary heart disease (the primary end point) with the effects of placebo
      among 9014 patients with a history of myocardial infarction or unstable angina
      and a total cholesterol level of 155 to 271 mg per deciliter (4.0 to 7.0 mmol per
      liter). Our goal in the present study was to assess effects on stroke from any
      cause and nonhemorrhagic stroke, which were secondary end points. RESULTS: There
      were 419 strokes among 373 patients over a follow-up period of six years. A total
      of 309 strokes were classified as ischemic, 31 as hemorrhagic, and 79 as of
      unknown type. Among the patients given placebo, the risk of stroke was 4.5
      percent, as compared with 3.7 percent among those given pravastatin (relative
      reduction in risk, 19 percent; 95 percent confidence interval, 0 to 34 percent;
      P=0.05). Non-hemorrhagic stroke occurred in 4.4 percent of the patients given
      placebo, as compared with 3.4 percent of those given pravastatin (reduction in
      risk, 23 percent; 95 percent confidence interval, 5 to 38 percent; P=0.02).
      Pravastatin had no effect on hemorrhagic stroke (incidence, 0.2 percent in the
      placebo group vs. 0.4 percent in the pravastatin group; P=0.28). CONCLUSIONS:
      Pravastatin has a moderate effect in reducing the risk of stroke from any cause
      and the risk of nonhemorrhagic stroke in patients with previous myocardial
      infarction or unstable angina.

PMID- 10922422
TI  - Hepatic iron concentration and total body iron stores in thalassemia major.
AB  - BACKGROUND AND METHODS: We tested the usefulness of measuring the hepatic iron
      concentration to evaluate total body iron stores in patients who had been cured
      of thalassemia major by bone marrow transplantation and who were undergoing
      phlebotomy treatment to remove excess iron. RESULTS: We began treatment with
      phlebotomy a mean (+/-SD) of 4.3+/-2.7 years after transplantation in 48 patients
      without hepatic cirrhosis. In the group of 25 patients with liver-biopsy samples
      that were at least 1.0 mg in dry weight, there was a significant correlation
      between the decrease in the hepatic iron concentration and total body iron stores
      (r=0.98, P<0.001). Assuming that the hepatic iron concentration is reduced to
      zero with complete removal of body iron stores during phlebotomy, the amount of
      total body iron stores (in milligrams per kilogram of body weight) is equivalent
      to 10.6 times the hepatic iron concentration (in milligrams per gram of liver,
      dry weight). With the use of this equation, we could reliably estimate total body
      iron stores as high as 250 mg per kilogram of body weight, with a standard error
      of less than 7.9. CONCLUSIONS: The hepatic iron concentration is a reliable
      indicator of total body iron stores in patients with thalassemia major. In
      patients with transfusion-related iron overload, repeated determinations of the
      hepatic iron concentration can provide a quantitative means of measuring the long
      term iron balance.

PMID- 10922423
TI  - Low-dose inhaled corticosteroids and the prevention of death from asthma.
AB  - BACKGROUND: Although inhaled corticosteroids are effective for the treatment of
      asthma, it is uncertain whether their use can prevent death from asthma. METHODS:
      We used the Saskatchewan Health data bases to form a population-based cohort of
      all subjects from 5 through 44 years of age who were using antiasthma drugs
      during the period from 1975 through 1991. We followed subjects until the end of
      1997, their 55th birthday, death, emigration, or termination of health insurance
      coverage; whichever came first. We conducted a nested case-control study in which
      subjects who died of asthma were matched with controls within the cohort
      according to the length of follow-up at the time of death of the case patient
      (the index date), the date of study entry, and the severity of asthma. We
      calculated rate ratios after adjustment for the subject's age and sex; the number
      of prescriptions of theophylline, nebulized and oral beta-adrenergic agonists,
      and oral corticosteroids in the year before the index date; the number of
      canisters of inhaled beta-adrenergic agonists used in the year before the index
      date; and the number of hospitalizations for asthma in the two years before the
      index date. RESULTS: The cohort consisted of 30,569 subjects. Of the 562 deaths,
      77 were classified as due to asthma. We matched the 66 subjects who died of
      asthma for whom there were complete data with 2681 controls. Fifty-three percent
      of the case patients and 46 percent of the control patients had used inhaled
      corticosteroids in the previous year, most commonly low-dose beclomethasone. The
      mean number of canisters was 1.18 for the patients who died and 1.57 for the
      controls. On the basis of a continuous dose-response analysis, we calculated that
      the rate of death from asthma decreased by 21 percent with each additional
      canister of inhaled corticosteroids used in the previous year (adjusted rate
      ratio, 0.79; 95 percent confidence interval, 0.65 to 0.97). The rate of death
      from asthma during the first three months after discontinuation of inhaled
      corticosteroids was higher than the rate among patients who continued to use the
      drugs. CONCLUSIONS: The regular use of low-dose inhaled corticosteroids is
      associated with a decreased risk of death from asthma.

PMID- 10922424
TI  - Innate immunity.

PMID- 10922425
TI  - The red eye.

PMID- 10922426
TI  - Clinical problem-solving. QT or not QT?

PMID- 10922427
TI  - Omeprazole to prevent recurrent bleeding after endoscopic treatment of ulcers.

PMID- 10922428
TI  - Ulysses and the fate of frozen embryos--reproduction, research, or destruction?

PMID- 10922429
TI  - Follow-up study of patients randomized in the Scandinavian simvastatin survival
      study (4S) of cholesterol lowering.
AB  - The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical
      trials have demonstrated that cholesterol-lowering treatment with statins
      improves prognosis in patients with coronary atherosclerosis compared with
      placebo. The effect of therapy with statins beyond the typical 5 to 6 years'
      duration of the trials, in particular regarding the risk of cancer, has not been
      investigated. This study examines the long-term effects of simvastatin for up to
      8 years on cause-specific mortality in patients with coronary heart disease
      (CHD). We performed an observational, government registry-based study of
      mortality in the groups originally randomized to simvastatin or placebo in the 4S
      over an additional 2-year follow-up period, so that the median total follow-up
      period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took
      place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland,
      Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221
      were randomized to treatment with placebo or simvastatin therapy, respectively.
      Patients received treatment with simvastatin, starting at 20 mg/day, with
      titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L
      (200 mg/dl), or placebo. After the double-blind period, most patients in both
      treatment groups received simvastatin as open-label prescription. Of the 1,967
      patients originally treated with placebo and surviving the double-blind period,
      97 (4.9%) died during the following 2 years. In the group randomized to
      simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%).
      Adding these deaths to those occurring during the original trial, the total was
      353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo
      and simvastatin, respectively. The relative risk was 0.70 (95% confidence
      interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68
      (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk
      0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of
      noncardiovascular and other deaths were similar in both groups. We therefore
      conclude that treatment with simvastatin for up to 8 years in patients with CHD
      is safe and yields continued survival benefit.

PMID- 10922430
TI  - Fibrin specificity and procoagulant effect related to the kallikrein-contact
      phase system and to plasmin generation with double-bolus reteplase and front
      loaded alteplase thrombolysis in acute myocardial infarction.
AB  - This study was undertaken to compare the effects of reteplase and alteplase
      regimens on hemostasis and fibrinolysis in acute myocardial infarction (AMI).
      Thrombolytic treatment in patients with AMI is hampered by paradoxical
      procoagulant effects that favor early reocclusion. In vivo data comparing this
      effect and the fibrin specificity of double-bolus reteplase and front-loaded
      alteplase regimens are not available. In a prospective, randomized study, 50
      patients with AMI were either treated with double bolus (10 + 10 U) reteplase or
      with front-loaded alteplase (up to 100 mg) within 6 hours of symptom onset.
      Thirty apparently healthy persons served as controls. Molecular markers of
      coagulation and fibrinolysis were serially examined for up to 5 days. Paradoxical
      thrombin activation at 3 hours after initiation of therapy was comparable between
      reteplase and alteplase. Reteplase (65 +/- 5 U/L) and alteplase (72 +/- 8 U/L)
      caused significantly elevated kallikrein activity at 3 hours after adminstration
      (p <0.01 vs controls 30 +/- 1 U/L). Fibrin specificity was less for reteplase (p
      <0.05) with a decrease in fibrinogen at 3 hours to 122 +/- 27 mg/dl versus 224 +/
      28 mg/dl for alteplase (p <0.01 and p <0.05 vs controls). D-Dimer levels at 3
      hours were higher (p <0.05) after reteplase (5,459 +/- 611 ng/ml) versus
      alteplase (3,445 +/- 679 ng/ml) (both p <0.01 vs controls 243 +/- 17 ng/ml).
      Plasmin generation (plasmin-antiplasmin complexes) was significantly (p <0.01)
      increased at 3 hours with both regimens to 27,079 +/- 3,964 microg/L (reteplase)
      and 19,522 +/- 2,381 microg/L (alteplase). The data from 3 hours after start of
      thrombolytic therapy proved less marked fibrin specificity of the reteplase
      regimen (in vivo) compared with front-loaded alteplase. Both regimens have a
      moderate procoagulant effect without differences in activation of the kallikrein
      system.

PMID- 10922431
TI  - Synergy between intracoronary stenting and abciximab in improving angiographic
      and clinical outcomes of primary angioplasty in acute myocardial infarction.
AB  - This study examined 650 consecutive patients who presented with an acute
      myocardial infarction and were treated with primary angioplasty within 12 hours
      of symptom onset between August 1995 and December 1998. Patients were placed into
      4 treatment groups depending on the adjunctive therapy they received: group 1,
      percutaneous transluminal coronary angioplasty (PTCA) ("balloon PTCA alone"; n =
      220); group 2, PTCA plus intracoronary stent placement ("stent"; n = 128); group
      3, PTCA plus abciximab therapy ("abciximab"; n = 104); and group 4, PTCA plus
      intracoronary stent placement plus abciximab therapy ("stent/abciximab"; n =
      198). The patients' clinical characteristics, severity of disease, and total
      ischemia time on presentation were similar. At baseline, abciximab and
      stent/abciximab groups had a higher incidence of thrombus on coronary
      angiography. Postprocedural quantitative coronary analysis showed a significantly
      larger minimum luminal diameter in the stent and stent/abciximab groups than PTCA
      alone. Overall, stents were most efficacious in reducing target vessel
      revascularization rate, whereas abciximab was associated with a higher
      postprocedural Thrombolysis In Myocardial Infarction-3 trial flow and less "no
      reflow." The best angiographic result was achieved in the stent/abciximab group.
      Similarly, the primary combined end point of death, myocardial infarction, and
      target vessel revascularization at 30 days was the lowest (6.1%) in the
      stent/abciximab group. The combination of abciximab and stenting in primary
      angioplasty for acute myocardial infarction is thus synergistic and is associated
      with improved angiographic and clinical results at 30-day follow-up.

PMID- 10922432
TI  - Long-term effects of diltiazem and verapamil on mortality and cardiac events in
      non-Q-wave acute myocardial infarction without pulmonary congestion: post hoc
      subset analysis of the multicenter diltiazem postinfarction trial and the second
      danish verapamil infarction trial studies.
AB  - The main objective of this retrospective analysis was to evaluate the long-term
      effect of the heart rate-lowering calcium antagonists verapamil and diltiazem on
      the incidence of combined cardiac events and all-cause mortality in patients who
      had experienced a non-Q-wave acute myocardial infarction (AMI), but who did not
      also have pulmonary congestion. In addition, factors having an independent
      association with these 2 outcomes were identified. Of 817 non-Q-wave patients, 81
      (9.9%) died during 12 to 52 months of follow-up. The unadjusted mortality rate
      was 42% lower in patients randomized to calcium antagonist therapy than placebo
      (7.2% vs 12.4%, p = 0.010). Non-Q-wave patients who died during follow-up were
      older than patients who survived (62 vs 58 years, p = 0.001). Other factors found
      to have an independent association with all-cause mortality included diuretic use
      (RR 2.79), diabetes mellitus (RR 2.86), and New York Heart Association class >I
      (RR 1.73). The covariate adjusted all-cause mortality risk ratio associated with
      randomization to calcium antagonist therapy was 0.65 (95% confidence interval
      [0.40 to 1.05, p = 0.079]). Overall, 153 patients (18.7%) died or had nonfatal
      reinfarction. The unadjusted combined event rate was 31% lower in patients
      randomized to calcium antagonist therapy than to placebo (15.2% vs 21.9%, p
      <0.006). Factors found to have an independent association with cardiac events
      included age, diabetes (RR 2.82), diuretic use (RR 2.04), and previous AMI (RR 1.
      71). In addition, randomization to the calcium antagonist group had a significant
      independent association with reduced cardiac events (p = 0.031). The covariate
      adjusted event rate RR associated with randomization to the calcium antagonist
      group was 0.69 (95% confidence interval [0.49 to 0.97]). In conclusion, the heart
      rate-lowering calcium antagonists diltiazem and verapamil may play an important
      role in reducing long-term mortality and reinfarction in non-Q-wave AMI without
      pulmonary congestion.

PMID- 10922433
TI  - Ankle/brachial blood pressure in men >70 years of age and the risk of coronary
      heart disease.
AB  - Low ankle/brachial blood pressure index (ABI) is a marker of generalized
      atherosclerosis in the elderly, although its association with coronary heart
      disease (CHD) has not been well established. The purpose of this report is to
      examine the relation between ABI and the risk of CHD in a sample of elderly men.
      Findings are based on the ABI that was measured in 2,863 Japanese-American men
      aged 71 to 93 years at an examination that occurred from 1991 to 1993 in the
      Honolulu Heart Program. All men were free of total CHD at that time and followed
      for nonfatal myocardial infarction and death from CHD over a 3- to 6-year period.
      During follow-up, 186 had a coronary event. Age-adjusted incidence declined
      significantly from 15.3% in men with an ABI <0.8 to 5.4% in men with an ABI
      >/=1.0 (p <0.001). The effect of ABI on disease was similar across a variety of
      risk factor strata, although it seemed strongest in the presence of hypertension
      and in past and current cigarette smokers. Adjustment for other risk factors
      failed to diminish the relation between ABI and CHD. We conclude that a low ABI
      increases the risk of CHD in elderly men. If findings can be extended to other
      elderly population segments, simple measurement of ABI in an outpatient setting
      could be an important tool for assessing the risk of CHD in the elderly.

PMID- 10922434
TI  - Relation of serum triglyceride levels to survival after coronary artery bypass
      grafting.
AB  - We performed a prospective observational study on 6,602 subjects (94% for 5 years
      and 34% for 10 to 15 years) who underwent coronary artery bypass graft surgery
      (CABG) between 1982 and 1992. We examined whether triglyceride concentrations
      adjusted for other factors (total cholesterol, history of diabetes mellitus,
      systemic hypertension, left ventricular function, number of coronary arteries
      significantly narrowed, and use of the internal thoracic arteries) explained
      total and event-free survival. These analyses were duplicated within gender
      (1,354 women and 5,248 men). This approach allowed a determination of any gender
      related disparities in lipid predictors. Triglycerides in the highest quartile
      were associated with an increased risk of mortality of 20% (confidence interval
      [CI] 1.0 to 1.4). Similar risk was seen for event-free survival. Although there
      was no evidence of gender differences in adjusted survival (p = 0.33), a gender
      by triglyceride interaction (p = 0.004) indicated that the response to high
      triglycerides as related to survival did differ by gender. Specifically, women
      had a dramatically higher risk (hazard ratio [HR] 1.5, CI 1.1 to 2.1) than men
      (HR 1.1, CI 0.9 to 1. 3). Both men and women did have triglyceride-associated
      risk with regard to event-free survival (HR in men 1.2, CI 1.1 to 1.4; HR in
      women 1.4, CI 1.1 to 1.8). Examination of high-density lipoprotein cholesterol in
      a subcohort did not eliminate the observed triglyceride effects. Thus,
      triglyceride baseline values are primary determinants (similar to baseline left
      ventricular function or extent of coronary disease) for long-term total and event
      free mortality after CABG in women but not in men.

PMID- 10922435
TI  - Identification of patients at risk by graded exercise testing in an emergency
      department chest pain center.
AB  - The study applied a retrospective follow-up design to determine the prognostic
      effect of graded exercise testing (GXT) in patients with low- to moderate-risk
      chest pain evaluated in an emergency department 9-hour protocol chest pain center
      (CPC) from January 1, 1993 to August 1, 1996. The cohort of 1,209 patients were
      followed to the date of death or first adverse cardiac event up to 1 year after
      CPC admission. Cardiac events were defined as coronary artery bypass graft,
      percutaneous transluminal coronary angioplasty, cardiogenic shock, cardiac
      related death, congestive heart failure admission, ventricular
      tachycardia/ventricular fibrillation arrest, and myocardial infarction. Patients
      with acute ST-segment elevation or depression of >1 mm, positive enzyme (creatine
      kinase myocardial band) testing, or unstable angina during their CPC evaluation
      were admitted without GXT testing. Statistical analysis included chi-square test
      for complication rates and Cox proportional-hazards modeling. Nine hundred fifty
      eight of 1,209 patients underwent GXT testing. Patients with positive,
      inconclusive, and normal GXTs had complication rates of 36.8% (7 of 19), 3.4% (9
      of 267), and 1.1% (5 of 456), respectively. After adjusting for age, sex, and
      race, the relative risk of complication was 38.9 (95% confidence interval 11.7 to
      129.6) with a positive GXT, and 3.6 (95% confidence interval 1.2 to 10.7) with an
      inconclusive GXT compared with a normal GXT. The GXT is a good prognostic
      indicator of adverse cardiac events in low- to moderate-risk chest pain in
      patients evaluated in an emergency department CPC.

PMID- 10922436
TI  - Comparison of simultaneous dobutamine echocardiography and thallium-201 stress
      reinjection single-photon emission computed tomography in predicting improvement
      of chronic myocardial dysfunction after revascularization.
AB  - Previous studies have shown that ultrasonic integrated backscatter is valuable in
      characterizing stunned myocardium. Recent investigations have demonstrated that
      resting cardiac cycle-dependent variation of integrated backscatter closely
      paralleled the contractile reserve in patients with chronic left ventricular
      ischemic dysfunction. The purpose of this study was to validate whether
      ultrasonic tissue characterization (UTC) compared with dobutamine stress
      echocardiography (DSE) and thallium-201 stress-reinjection single-photon emission
      computed tomography (Tl-SPECT) could predict reversible myocardial dyssynergy in
      patients with chronic coronary artery disease. Forty-eight patients with stable
      coronary artery disease underwent UTC, DSE, and Tl-SPECT simultaneously before
      successful coronary revascularization and were followed up with echocardiograms
      at rest >3 months later. Among the 58 investigated segments, the weighted
      amplitude, a composite parameter derived from the integrated backscatter power
      curve, was larger for those groups with greater functional recovery (p <0.001).
      For the persistent akinetic segments, the weighted amplitudes were small with
      large deviations of the nadir ratios that represented the asynchrony between the
      intramural contractile events and the global systole. Using the cut-off value 2.0
      of the weighted amplitude, the sensitivity and specificity for predicting
      functional improvement after revascularization were both 82.8% (kappa = 0.66) and
      comparable to the sensitivity and specificity of DSE and Tl-SPECT. UTC,
      delineating the myocardial physical state and intramural contraction, can be a
      novel approach in predicting functional improvement of chronic dyssynergy after
      revascularization.

PMID- 10922437
TI  - Population frequency distribution of non-high-density lipoprotein cholesterol
      (Third National Health and Nutrition Examination Survey [NHANES III], 1988-1994).
AB  - The objective of this study was to provide population frequency distribution data
      for non-high-density lipoprotein (HDL) cholesterol (total cholesterol minus HDL
      cholesterol) concentrations and to evaluate whether differences exist by gender,
      ethnicity, or level of education. Serum levels of non-HDL cholesterol and
      sociodemographic characteristics were determined for 3,618 black, 3,528 Mexican
      American, and 6,043 white women and men, aged >/=25 years, from a national cross
      sectional survey of the US population (National Health And Nutrition Examination
      Survey III, 1988-1994). Age-adjusted non-HDL cholesterol concentrations were
      lower in women than men (154.1 vs 160.4 mg/dL, p <0.001). In women and men, age
      was positively associated with non-HDL cholesterol in the 25 to 64-year age
      range, and the slope of the association was steeper for women. For women and men
      >/=65 years, age was negatively associated with non-HDL cholesterol, and the
      slope of the association was steeper for men. Black women and men had lower non
      HDL cholesterol levels than either Mexican-American or white women and men
      (women, p <0.02; men, p <0.001, for both ethnic contrasts). Women with less
      education had higher levels of non-HDL cholesterol than women with more education
      (p <0.01). These nationally representative population frequency distribution data
      provide non-HDL cholesterol reference levels for clinicians and investigators and
      indicate that there are significant variations in non-HDL cholesterol by gender,
      age, ethnicity, and level of education.

PMID- 10922438
TI  - Evaluation of coronary flow reserve in hypertensive patients by dipyridamole
      transesophageal doppler echocardiography.
AB  - This study evaluates the coronary flow reserve (CFR) in hypertensive patients
      with and without left ventricular (LV) hypertrophy. CFR was assessed by
      transesophageal Doppler echocardiography in 15 normal subjects (group I), 21
      hypertensive patients without LV hypertrophy (group II), and 27 hypertensive
      patients with LV hypertrophy (group III). All hypertensive patients were
      complaining of typical anginal pain and had normal coronary angiograms. The
      sample volume was placed at the bifurcation of the left main and left anterior
      descending coronary arteries. Coronary blood flow velocities were evaluated at
      rest, 2 minutes after dipyridamole infusion, and 2 minutes after intravenous
      aminophylline. The ratios of dipyridamole to rest peak diastolic and systolic
      velocities were considered as indexes of CFR. Peak diastolic velocity ratio was
      significantly lower in group III than in groups I and II (1.6 +/- 0.2, 2.7 +/-
      0.4, and 2.1 +/- 0.2, respectively; p <0.05), and it was significantly lower in
      group II than I (p <0.05). The peak systolic velocity ratio was significantly
      lower in group III than in groups I and II (1.7 +/- 0.3, 2.8 +/- 0.3, and 2.1 +/-
      0.2, respectively; p <0.05), and it was significantly lower in group II than I (p
      <0.05). The peak diastolic velocity ratio was inversely related to systolic blood
      pressure, diastolic blood pressure, and LV mass index (r = -0.48, -0. 51, and 
      0.37 respectively) in hypertensive patients. It is concluded that CFR is
      significantly impaired in hypertensive patients, especially those with LV
      hypertrophy, compared with healthy subjects. The degree of impairment of CFR is
      related to LV mass index.

PMID- 10922439
TI  - Association of hyperglycemia with reduced heart rate variability (The Framingham
      Heart Study).
AB  - This study was designed to examine the association of heart rate variability
      (HRV) with blood glucose levels in a large community-based population. Previous
      reports have shown HRV to be reduced in diabetics, suggesting the presence of
      abnormalities in neural regulatory mechanisms. There is scant information about
      HRV across the spectrum of blood glucose levels in a population-based cohort. One
      thousand nine hundred nineteen men and women from the Framingham Offspring Study,
      who underwent ambulatory electrocardiographic recordings at a routine
      examination, were eligible. HRV variables included the SD of normal RR intervals
      (SDNN), high-frequency (HF, 0.15 to 0.40 Hz) and low-frequency (LF, 0.04 to 0.15
      Hz) power, and LF/HF ratio. Fasting plasma glucose levels were used to classify
      subjects as normal (<110 mg/dl; n = 1, 779), as having impaired fasting glucose
      levels (110 to 125 mg/dl; n = 56), and as having diabetes mellitus (DM >/=126
      mg/dl or receiving therapy; n = 84). SDNN, LF and HF power, and LF/HF ratio were
      inversely related to plasma glucose levels (p <0.0001). SDNN and LF and HF powers
      were reduced in DM subjects (4.28 +/- 0.03, 6.03 +/- 0. 08, and 4.95 +/- 0.09)
      and in subjects with impaired fasting glucose levels (4.37 +/- 0.04, 6.26 +/-
      0.10, and 5.06 +/- 0.11) compared with those with normal fasting glucose (4.51 +/
      0.01, 6.77 +/- 0.02, and 5.55 +/- 0.02, all p <0.005), respectively. After
      adjusting for covariates (age, sex, heart rate, body mass index, antihypertensive
      and cardiac medications, systolic and diastolic blood pressures, smoking, and
      alcohol and coffee consumption), LF power and LF/HF ratio were lower in DM
      subjects than in those with normal fasting glucose (p <0.005). HRV is inversely
      associated with plasma glucose levels and is reduced in diabetics as well as in
      subjects with impaired fasting glucose levels. Additional research is needed to
      determine if low HRV contributes to the increased cardiovascular morbidity and
      mortality described in subjects with hyperglycemia.

PMID- 10922440
TI  - Evaluation of calibration methods for size estimation in the pediatric cardiac
      catheterization laboratory.
AB  - Limited data are available on the accuracy of various calibration methods used to
      estimate the size of cardiovascular structures during interventional pediatric
      cardiac catheterizations. The aim of this study was to evaluate, in an
      experimental model, several of these commonly used calibration methods. Thoracic
      box models were constructed in 4 sizes to simulate average chest sizes of
      infants, children, adolescents, and adults. Four anatomic positions were studied:
      aortic valve in posteroanterior projection, pulmonary valve in lateral
      projection, and isthmus in posteroanterior and lateral projections. The following
      calibration methods were examined: (1) a 5Fr pigtail catheter or a 1-cm radio
      opaque marker catheter, placed at the level of the anatomic structure, (2) a body
      surface marker in multiple positions, and (3) a 1 x 1-cm radio-opaque rectilinear
      grid placed either at the center of the thorax or in an anatomic position. Three
      independent observers made size estimations. The most accurate method for size
      estimation, in all anatomic positions and for all box sizes, was the 1-cm radio
      opaque marker catheter (mean error </=4%). The surface marker was moderately
      accurate in the smallest box (mean error 3% to 6%), but had a mean error as high
      as 33% in the adult-sized box. The 5Fr pigtail angiographic catheter
      overestimated the size of the structure by 3% to 13% (mean 7%). Intra- and
      interobserver differences in size estimations were not statistically significant.
      Among the size calibration methods used during pediatric cardiac
      catheterizations, catheters with radio-opaque markers within the structure of
      interest were the most accurate. The use of surface markers in larger patients
      may introduce significant error, risking a potentially inadequate or adverse
      outcome from the intervention.

PMID- 10922441
TI  - Influence of ventricular morphology on outcome after the Fontan procedure.
AB  - The modified Fontan procedure has gained wide acceptance in the treatment of
      various congenital heart defects. Determination of risk factors for mortality
      remains an important issue for optimizing patient selection for the Fontan
      procedure. Conflicting results have been reported about whether ventricular
      morphology is a risk factor in these patients. Survival free of Fontan takedown
      or cardiac transplantation was assessed in the first 500 patients undergoing the
      Fontan procedure at our institution. This survival was correlated with
      ventricular morphology as evaluated by angiography. Both multivariate and
      univariate analyses indicated ventricular morphology was predictive of early
      survival free of Fontan takedown or cardiac transplantation following the
      procedure. However, there was no statistical evidence for ventricular morphology
      being a risk factor for mortality in patients alive 6 months after the procedure.
      Ventricular morphology is a risk factor for early survival in patients undergoing
      a Fontan procedure, with left ventricular morphology associated with a better
      early survival than right ventricular morphology.

PMID- 10922442
TI  - Initial energy for electrical cardioversion of atrial fibrillation-is more
      better?

PMID- 10922443
TI  - Cardioversion of atrial fibrillation to sinus rhythm: who, when, how, and why?

PMID- 10922444
TI  - Effects of age, sex, race, diagnosis-related group, and hospital setting on lipid
      management in patients with coronary artery disease.
AB  - Among 1,211 patients hospitalized with documented CAD at either a university
      hospital or a large suburban community hospital, 36% failed to receive
      appropriate evaluation and treatment for dyslipidemia. Younger patients, those
      admitted to a university hospital, and those undergoing percutaneous coronary
      intervention were substantially more likely to receive appropriate lipid
      management than other subgroups.

PMID- 10922445
TI  - Long-term (three years) effect of estrogen replacement therapy on major adverse
      cardiac events in postmenopausal women after intracoronary stenting.
AB  - This study examined whether estrogen replacement therapy (ERT) in postmenopausal
      women impacts intermediate and long-term outcome after successful coronary
      stenting. Our findings offer evidence that ERT significantly reduces target
      lesion revascularization after intracoronary stenting in postmenopausal patients
      who are on ERT before the intervention.

PMID- 10922446
TI  - Noninvasive risk stratification in women with uncomplicated acute myocardial
      infarction.
AB  - The aim of our study was to compare the prognostic value of stress
      echocardiography and exercise electrocardiography after uncomplicated non-Q-wave
      acute myocardial infarction in a series of 89 female patients. Our data show that
      stress echocardiography has independent predictive value in a female patient
      population recovering from uncomplicated acute myocardial infarction.

PMID- 10922447
TI  - Usefulness of stent length in predicting in-stent restenosis (the MULTI-LINK
      stent trials).
AB  - The cumulative experience of 4 clinical trials using the MULTI-LINK coronary
      stent design was analyzed. Multivariable logistic regression identified
      postprocedure in-stent minimum lumen diameter (p = 0.0001), stent length (p =
      0.0038), smoking (p = 0.0105). and diabetes (p = 0.0803) as the most important
      predictors of in-stent restenosis at late (6- to 9-month) angiographic follow-up.

PMID- 10922448
TI  - Usefulness of ST elevation II/III ratio and ST deviation in lead I for
      identifying the culprit artery in inferior wall acute myocardial infarction.
AB  - In a study of 92 patients presenting with inferior wall acute myocardial
      infarction, the infarct-related artery was the right coronary artery in 72
      patients (78%) and the left circumflex artery in 20 (22%). An ST II/III ratio of
      1 or an isoelectric ST in lead I are sensitive and specific markers of left
      circumflex artery occlusion, whereas an ST II/III ratio <1 (ST elevation in lead
      III >II) or ST depression in lead I are sensitive and specific markers of right
      coronary artery occlusion.

PMID- 10922449
TI  - Polytetrafluoroethylene-covered stent for the treatment of narrowings in
      aorticocoronary saphenous vein grafts.
AB  - We compared the outcome of patients with saphenous graft disease treated with
      polytetrafluoroethylene (PTFE)-covered stents or noncovered stents. Angiographic
      success was similar; non-Q-wave myocardial infarction was lower in the PTFE group
      (p = 0.06) and long-term major cardiac events and restenosis rate were similar in
      the 2 groups. Implantation of PTFE-covered stent in vein graft disease seems to
      reduce the occurrence of distal embolization.

PMID- 10922450
TI  - Increased plasma homocysteine is an independent predictor of new coronary events
      in older persons.
AB  - A prospective study investigated the association of plasma homocysteine and other
      risk factors with the incidence of new coronary events at 31 +/- 9 month follow
      up in 153 men and 347 women, mean age 81 +/- 9 years. The stepwise Cox regression
      model showed that significant independent predictors of new coronary events in
      older persons were age (risk ratio 1.041), plasma homocysteine (risk ratio
      1.073), current cigarette smoking (risk ratio 2.524), hypertension (risk ratio
      2.032), diabetes mellitus (risk ratio 2.022), serum total cholesterol (risk ratio
      1.013), serum high-density lipoprotein cholesterol (risk ratio 0.925), and serum
      triglycerides (risk ratio 1.004).

PMID- 10922451
TI  - Initial energy for elective external cardioversion of persistent atrial
      fibrillation.
AB  - We conducted a prospective randomized study to determine the safety and efficacy
      rate of 3 commonly used energy levels (100, 200, and 360 J) for elective direct
      current cardioversion of persistent atrial fibrillation. When compared with 100
      and 200 J, the initial success rate with 360 J was significantly higher (14%,
      39%, and 95%, respectively), and patients randomized to 360 J ultimately required
      less total energy and a lower number of shocks.

PMID- 10922452
TI  - Clinical, echocardiographic, and hormonal factors influencing spontaneous
      conversion of recent-onset atrial fibrillation to sinus rhythm.
AB  - The present study was designed to determine clinical, hormonal, and
      echocardiographic factors influencing spontaneous conversion to sinus rhythm of
      recent-onset atrial fibrillation (symptoms <6 hours). The most important
      predictor of spontaneous conversion was the time of onset of atrial fibrillation;
      patients who developed the arrhythmia during sleep had the highest probability of
      spontaneous conversion during the first 24 hours. A second predictor was the
      plasma concentration of atrial natriuretic peptide during the arrhythmia.

PMID- 10922453
TI  - Comparison of one-year outcome in women versus men with chronic congestive heart
      failure.
AB  - Using information from the Italian Network on Congestive Heart Failure, we
      examined whether clinical epidemiologic characteristics, drug prescription
      patterns, and outcome of patients with congestive heart failure differed
      according to sex and whether gender was an independent risk factor for mortality
      and hospital admissions.

PMID- 10922454
TI  - Evaluation of a noninvasive index of global ventricular function to predict
      rejection after pediatric cardiac transplantation.
AB  - A Doppler myocardial performance index, defined as the sum of the isovolumetric
      contraction and relaxation time divided by the ejection time (ICT + IRT/ET),
      reflects global cardiac function, and when applied to the left ventricle, may
      serve as a predictor of moderate rejection in pediatric cardiac transplant
      patients.

PMID- 10922455
TI  - Late follow-up after thoracoscopic ductal ligation.
AB  - Interventional catheterization and minimally invasive surgical techniques offer
      the real possibility of a reduction in cost and morbidity when compared with the
      traditional surgical approach to patent ductus arteriosus. Video-assisted
      thoracoscopic surgery may prove to be a superior technique because of its
      application to a wider range of patients needing ductal closure, a lower
      incidence of residual shunting, no evidence for recurrent shunting, and the
      absence of intravascular foreign bodies.

PMID- 10922456
TI  - Malignant cardiac tamponade in women with breast cancer treated by
      pericardiocentesis and intrapericardial administration of
      triethylenethiophosphoramide (thiotepa).
AB  - We treated 19 women with malignant cardiac tamponade due to advanced breast
      cancer with subxiphoid pericardiocentesis and local thiotepa instillation. The
      method has no serious side effects, prevents pericardial fluid reaccumulation,
      and, combined with systemic adjuvant therapy, prolongs survival.

PMID- 10922457
TI  - Relation of blunted dilation of the brachial artery in insulin-dependent diabetes
      mellitus to microalbuminuria.
AB  - Endothelium-dependent vasodilation in the conduit peripheral arteries of patients
      with insulin-dependent diabetes mellitus is impaired and is closely related to
      microalbuminuria. The diabetic state does not significantly influence the
      vascular smooth muscle functional capability.

PMID- 10922458
TI  - Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine
      paradox.
AB  - L-Arginine, the substrate of nitric oxide (NO) synthases (NOSs), is found in the
      mammalian organism at concentrations by far exceeding K(M) values of these
      enzymes. Therefore, additional L-arginine should not enhance NO formation. In
      vivo, however, increasing L-arginine concentration in plasma has been shown
      repeatedly to increase NO production. This phenomenon has been named the L
      arginine paradox; it has found no satisfactory explanation so far. In the present
      work, evidence for the hypothesis that the endogenous NOS inhibitors
      methylarginines, asymmetric dimethylarginine being the most powerful (IC(50) 1.5
      microM), are responsible for the L-arginine paradox is presented.

PMID- 10922460
TI  - Cell type specific localization of sphingomyelin biosynthesis.
AB  - We have studied the incorporation of [(14)C]serine and of [(3)H]sphingosine into
      sphingomyelin in the presence or absence of brefeldin A (BFA) in three different
      cell types. Administration of BFA (1 microgram/ml) to fibroblasts for 24 h
      increased the incorporation of label into sphingomyelin 1.5-3 fold compared with
      untreated controls. In contrast, BFA strongly decreased sphingomyelin
      biosynthesis (4-5 fold) in cerebellar neurons as well as in neuroblastoma cells.
      The effect of BFA on glycosphingolipid formation, however, was similar in all
      three cell types studied: an increased labeling of the precursor glycolipids
      GlcCer, LacCer, GM3 and GD3 was paralleled by a decreased formation of complex
      gangliosides, GM1, GD1a, GT1b and GQ1b. Our data therefore suggest that in
      neuronal cells sphingomyelin synthesis, like the formation of complex
      gangliosides, is localized primarily distal to the BFA block, in a post-Golgi
      compartment, most probably the trans-Golgi network, whereas in fibroblasts
      sphingomyelin biosynthesis is mainly localized prior to the BFA block, in the
      Golgi apparatus, as has been shown for LacCer, GlcCer, GM3 and GD3 synthases.

PMID- 10922459
TI  - A 45 kDa protein related to PPARgamma2, induced by peroxisome proliferators, is
      located in the mitochondrial matrix.
AB  - Besides their involvement in the control of nuclear gene expression by activating
      several peroxisome proliferator-activated receptors (PPARs), peroxisome
      proliferators influence mitochondrial activity. By analogy with the previous
      characterization of a mitochondrial T3 receptor (p43), we searched for the
      presence of a peroxisome proliferator target in the organelle. Using several
      antisera raised against different domains of PPARs, we demonstrated by Western
      blotting, immunoprecipitation and electron microscopy experiments, that a 45 kDa
      protein related to PPARgamma2 (mt-PPAR) is located in the matrix of rat liver
      mitochondria. In addition, we found that the amounts of mt-PPAR are increased by
      clofibrate treatment. Moreover, in EMSA experiments mt-PPAR bound to a DR2
      sequence located in the mitochondrial D-loop, by forming a complex with p43.
      Last, studies of tissue-specific expression indicated that mt-PPAR is detected in
      mitochondria of all tissues tested except the brain in amounts positively related
      to p43 abundance. Besides their involvement in the control of nuclear gene
      expression by activating several peroxisome proliferator-activated receptors
      (PPARs), peroxisome proliferators influence mitochondrial activity. By analogy
      with the previous characterization of a mitochondrial T3 receptor (p43), we
      searched for the presence of a peroxisome proliferator target in the organelle.
      Using several antisera raised against different domains of PPARs, we demonstrated
      by Western blotting, immunoprecipitation and electron microscopy experiments,
      that a 45 kDa protein related to PPARgamma2 (mt-PPAR) is located in the matrix of
      rat liver mitochondria. In addition, we found that the amounts of mt-PPAR are
      increased by clofibrate treatment. Moreover, in EMSA experiments mt-PPAR bound to
      a DR2 sequence located in the mitochondrial D-loop, by forming a complex with
      p43. Last, studies of tissue-specific expression indicated that mt-PPAR is
      detected in mitochondria of all tissues tested except the brain in amounts
      positively related to p43 abundance.

PMID- 10922461
TI  - Membrane topology of the N-terminus of the Escherichia coli FtsK division
      protein.
AB  - The Escherichia coli FtsK protein targets the septum, is essential for cell
      division and may play a role in DNA partitioning. Computer modelling suggests
      that the first 180 amino acids of the protein are embedded in the cytoplasmic
      membrane by up to six transmembrane domains. We demonstrate, using gene fusions,
      that the N-terminus contains four transmembrane helices that link two periplasmic
      domains. The first periplasmic domain contains an HEXXH amino acid sequence
      characteristic of zinc metalloproteases. We show by mutation analysis that the
      conserved glutamic acid of the HEXXH sequence is essential for FtsK function
      during septation.

PMID- 10922462
TI  - Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine.
AB  - L-Carnitine facilitates the transport of fatty acids into the mitochondrial
      matrix where they are used for energy production. Recent studies have shown that
      L-carnitine is capable of protecting the heart against ischemia/reperfusion
      injury and has beneficial effects against Alzheimer's disease and AIDS. The
      mechanism of action, however, is not yet understood. In the present study, we
      found that in Jurkat cells, L-carnitine inhibited apoptosis induced by Fas
      ligation. In addition, 5 mM carnitine potently inhibited the activity of
      recombinant caspases 3, 7 and 8, whereas its long-chain fatty acid derivative
      palmitoylcarnitine stimulated the activity of all the caspases.
      Palmitoylcarnitine reversed the inhibition mediated by carnitine. Levels of
      carnitine and palmitoyl-CoA decreased significantly during Fas-mediated
      apoptosis, while palmitoylcarnitine formation increased. These alterations may be
      due to inactivation of beta-oxidation or to an increase in the activity of the
      enzyme that converts carnitine to palmitoylcarnitine, carnitine
      palmitoyltransferase I (CPT I). In support of the latter possibility, fibroblasts
      deficient in CPT I activity were relatively resistant to staurosporine-induced
      apoptosis. These observations suggest that caspase activity may be regulated in
      part by the balance of carnitine and palmitoylcarnitine.

PMID- 10922463
TI  - Requirement of sphingolipid alpha-hydroxylation for fungicidal action of
      syringomycin E.
AB  - Syringomycin E is an antifungal cyclic lipodepsinonapeptide produced by
      Pseudomonas syringae pv. syringae. To understand the mechanism of action of
      syringomycin E, a novel resistant Saccharomyces cerevisiae strain, BW7, was
      isolated and characterized. Lipid analyses revealed that BW7 contained only the
      hydrophobic subspecies of sphingolipids that are normally minor components in
      wild type strains. This aberrant sphingolipid composition was the result of lack
      of alpha-hydroxylation of the amide-linked very long chain fatty acids,
      suggesting a defective sphingolipid alpha-hydroxylase encoded by the FAH1 gene. A
      yeast strain that lacks the FAH1 gene was resistant to syringomycin E, and failed
      to complement BW7. These results demonstrate that BW7 carries a mutation in the
      FAH1 gene, and that the lack of alpha-hydroxylated very long chain fatty acids in
      yeast sphingolipids confers resistance to syringomycin E.

PMID- 10922464
TI  - The redox state of endogenous pyridine nucleotides can determine both the degree
      of mitochondrial oxidative stress and the solute selectivity of the permeability
      transition pore.
AB  - Acetoacetate, an NADH oxidant, stimulated the ruthenium red-insensitive rat liver
      mitochondrial Ca(2+) efflux without significant release of state-4 respiration,
      disruption of membrane potential (Deltapsi) or mitochondrial swelling. This
      process is compatible with the opening of the currently designated low
      conductance state of the permeability transition pore (PTP) and, under our
      experimental conditions, was associated with a partial oxidation of the
      mitochondrial pyridine nucleotides. In contrast, diamide, a thiol oxidant,
      induced a fast mitochondrial Ca(2+) efflux associated with a release of state-4
      respiration, a disruption of Deltapsi and a large amplitude mitochondrial
      swelling. This is compatible with the opening of the high conductance state of
      the PTP and was associated with extensive oxidation of pyridine nucleotides.
      Interestingly, the addition of carbonyl cyanide p
      (trifluoromethoxy)phenylhydrazone to the acetoacetate experiment promoted a fast
      shift from the low to the high conductance state of the PTP. Both acetoacetate
      and diamide-induced mitochondrial permeabilization were inhibited by exogenous
      catalase. We propose that the shift from a low to a high conductance state of the
      PTP can be promoted by the oxidation of NADPH. This impairs the antioxidant
      function of the glutathione reductase/peroxidase system, strongly strengthening
      the state of mitochondrial oxidative stress.

PMID- 10922465
TI  - Inhibition of glucocorticoid-induced apoptosis by the expression of antisense
      gene of mitochondrial ATPase subunit 6(1).
AB  - To isolate the apoptosis-linked genes involved in the cell death of thymocytes
      induced by glucocorticoids, we developed a functional cloning assay. Murine
      CD4(+)CD8(+) thymic cell line 2-257-20 cells were transfected with cDNA
      expression libraries obtained from a dexamethasone-resistant cell line. The
      transfected cells were selected in the presence of dexamethasone, and the
      plasmids which episomally expanded were then extracted from the surviving cells.
      One of the rescued cDNAs was found to be an antisense cDNA fragment identical to
      the mouse mitochondrial ATPase 6 gene. In the stable transfectants with the
      ATPase 6 antisense gene, the induction of apoptosis by dexamethasone was
      significantly delayed. Furthermore, the ATP synthesis in these transfectants was
      also reduced to some extent. ATPase 6 is a subunit of F(o)F(1) ATPase and our
      results support that ATP synthesis from the mitochondria is necessary for the
      induction of apoptosis induced by glucocorticoids.

PMID- 10922466
TI  - Evidence that the substrate backbone conformation is critical to phosphorylation
      by p42 MAP kinase.
AB  - The effect of prolyl bond isomers on the substrate recognition capabilities of
      various endoproteases may be investigated in a reaction where both cis/trans
      isomers co-exist. Here we address the question of whether enzyme reactions at the
      side chain of an amino acid preceding proline proceed through an isomer specific
      pathway. The proline-directed p42 mitogen-activated protein kinase (ERK2) was
      used to phosphorylate the serine side chain in Pro-Arg-Ser-Pro-Phe-4-nitroanilide
      under conditions where different amounts of cis prolyl isomer of the substrate
      were present. Initial phosphorylation rates were calculated ranging between zero
      at 100% cis isomer and around 60 pM/min at the equilibrium content of 83.5% trans
      isomer. In the presence of the peptidyl-prolyl cis/trans isomerase human hFKBP12
      (500 nM), cis/trans isomerization proceeds rapidly, permitting the maximal
      phosphorylation rate to be observed in the dead time of the experiment. Results
      show that correct signature sequences are not sufficient to render potential
      substrates reactive to proline-directed enzymatic phosphorylations, but that the
      conformational state of the peptide bond following serine (threonine) is a
      critical determinant. Therefore, catalysis by peptidyl-prolyl cis/trans
      isomerases may add a new level of control to intracellular protein
      phosphorylations.

PMID- 10922467
TI  - Intersectin 2, a new multimodular protein involved in clathrin-mediated
      endocytosis.
AB  - Intersectin 1 (ITSN1) is a binding partner of dynamin that has been shown to
      participate in clathrin-mediated endocytosis. Here we report the characterization
      of a new human gene, ITSN2, highly similar to ITSN1. Alternative splicing of
      ITSN2 generates a short isoform with two EH domains, a coiled-coil region and
      five SH3 domains, and a longer isoform containing extra carboxy domains (DH, PH
      and C2 domains), suggesting that it could act as a guanine nucleotide exchange
      factor for Rho-like GTPases. ITSN2 expression analysis indicates that it is
      widely expressed in human tissues. Intersectin 2 isoforms show a subcellular
      distribution similar to other components of the endocytic machinery and co
      localize with Eps15. Moreover, their overexpression, as well as the corresponding
      ITSN1 protein forms, inhibits transferrin internalization.

PMID- 10922469
TI  - Activation of melanogenesis by vacuolar type H(+)-ATPase inhibitors in
      amelanotic, tyrosinase positive human and mouse melanoma cells.
AB  - In this study, we describe the activation of melanogenesis by selective vacuolar
      type H(+)-ATPase inhibitors (bafilomycin A1 and concanamycin A) in amelanotic
      human and mouse melanoma cells which express tyrosinase but show no
      melanogenesis. Addition of the inhibitors activated tyrosinase within 4 h, and by
      24 h the cells contained measurable amounts of melanin. These effects were not
      inhibited by cycloheximide (2 microgram/ml) which is consistent with a post
      translational mechanism of activation. Our findings suggest that melanosomal pH
      could be an important and dynamic factor in the control of melanogenesis in
      mammalian cells.

PMID- 10922468
TI  - Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage oligomeric
      matrix protein (COMP).
AB  - Matrix metalloproteinase (MMP)-19 and MMP-20 (enamelysin) are two recently
      discovered members of the MMP family. These enzymes are involved in the
      degradation of the various components of the extracellular matrix (ECM) during
      development, haemostasis and pathological conditions. Whereas MMP-19 mRNA is
      found widely expressed in body tissues, including the synovium of normal and
      rheumatoid arthritic patients, MMP-20 expression is restricted to the enamel
      organ. In this study we investigated the ability of MMP-19 and MMP-20 to cleave
      two of the macromolecules characterising the cartilage ECM, namely aggrecan and
      the cartilage oligomeric matrix protein (COMP). Both MMPs hydrolysed aggrecan
      efficiently at the well-described MMP cleavage site between residues Asn(341) and
      Phe(342), as shown by Western blotting using neo-epitope antibodies. Furthermore,
      the two enzymes cleaved COMP in a distinctive manner, generating a major
      proteolytic product of 60 kDa. Our results suggest that MMP-19 may participate in
      the degradation of aggrecan and COMP in arthritic disease, whereas MMP-20, due to
      its unique expression pattern, may primarily be involved in the turnover of these
      molecules during tooth development.

PMID- 10922470
TI  - Molecular dynamics simulation of four-alpha-helix bundles that bind the
      anesthetic halothane.
AB  - The mutation of a single leucine residue (L38) to methionine (M) is known
      experimentally to significantly increase the affinity of the synthetic four-alpha
      helix bundle (Aalpha(2))(2) for the anesthetic halothane. We present a molecular
      dynamics study of the mutant (Aalpha(2)-L38M)(2) peptide, which consists of a
      dimer of 62-residue U-shaped di-alpha-helical monomers assembled in an anti
      topology. A comparison between the simulation results and those obtained for the
      native (Aalpha(2))(2) peptide indicates that the overall secondary structure of
      the bundle is not affected by the mutation, but that the side chains within the
      monomers are better packed in the mutant structure. Unlike the native peptide,
      binding of a single halothane molecule to the hydrophobic core of (Aalpha(2)
      L38M)(2) deforms the helical nature of one monomer in a region close to the
      mutation site. Increased exposure of the cysteine side chain to the hydrophobic
      core in the mutant structure leads to the enhancement of the attractive
      interaction between halothane and this specific residue. Since the mutated
      residues are located outside the hydrophobic core the observed increased affinity
      for halothane appears to be an indirect effect of the mutation.

PMID- 10922471
TI  - Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.
AB  - We report the p35 and p60 forms of XRCC4 protein, appearing in human leukemia
      MOLT-4 or U937 cells following X-irradiation or hyperthermia. p35 appeared in
      conjunction with the cleavage of DNA-dependent protein kinase catalytic subunit
      (DNA-PKcs) and the fragmentation of internucleosomal DNA, and was suppressed by
      Ac-DEVD-CHO. p35 was also produced in vitro by treating MOLT-4 cell lysate with
      recombinant caspases, suggesting that p35 was a caspase-cleaved fragment of XRCC4
      in apoptotic cell death. p60 was sensitive to treatment with phosphatase or
      wortmannin and was undetectable in M059J cells deficient in DNA-PKcs. However,
      p60 was found in ataxia-telangiectasia cells after irradiation. These results
      indicated p60 as a phosphorylated form of XRCC4, requiring DNA-PKcs but not
      ataxia-telangiectasia mutated (ATM).

PMID- 10922472
TI  - In vivo localisation and stability of human Mcl-1 using green fluorescent protein
      (GFP) fusion proteins.
AB  - Mcl-1 is an anti-apoptotic member of the Bcl-2 family of proteins. We have
      expressed full length and mutated GFP:Mcl-1 fusion proteins to define structural
      motifs that control protein localisation and stability. When expressed in U-937
      cells, full length Mcl-1 locates primarily within mitochondria and its half-life
      was approximately 3 h, which was identical to the native, endogenously expressed
      protein. When the terminal 20 amino acids from the C-terminus of the protein were
      detected, the protein was diffused in the cytoplasm, but its stability was
      unaffected. This confirms that this region is responsible for efficient targeting
      to mitochondria. Surprisingly, deletion of 104 amino acids (residues 79-183) that
      contain putative PEST sequences and other stability regulating motifs, did not
      affect protein stability.

PMID- 10922473
TI  - Cloning and characterization of human histone deacetylase 8.
AB  - To date, seven different human histone deacetylases (HDACs) have been identified,
      which fall into two distinct classes. We have isolated and characterized a cDNA
      encoding a novel human HDAC, which we name HDAC8. HDAC8 shows a high degree of
      sequence similarity to HDAC1 and HDAC2 and thus belongs to the class I of HDACs.
      HDAC8 is expressed in a variety of tissues. Human cells overexpressing HDAC8
      localize the protein in sub-nuclear compartments whereas HDAC1 shows an even
      nuclear distribution. In addition, the HDAC8 gene is localized on the X
      chromosome at position q13, which is close to the XIST gene and chromosomal
      breakpoints associated with preleukemia.

PMID- 10922474
TI  - Characterization of the chitin biosynthesis process as a compensatory mechanism
      in the fks1 mutant of Saccharomyces cerevisiae.
AB  - Deletion of the 1,3-beta-D-glucan synthase gene FKS1 in Saccharomyces cerevisiae
      induces a compensatory mechanism that is reflected in a significant increase in
      chitin synthase III (CSIII) activity, leading to high rates of chitin synthesis.
      Deregulation of CSIII activity is mainly due to the intracellular delocalization
      of Chs3p and Chs4p, the two main components of the CSIII active complex.

PMID- 10922475
TI  - M-ABC2, a new human mitochondrial ATP-binding cassette membrane protein.
AB  - We have isolated a human cDNA encoding a novel ATP-binding cassette (ABC) protein
      whose gene was previously localized to chromosome 1q42 [Allikmets et al. (1995)
      Mamm. Genome 6, 111-117]. The gene transcript is expressed in all human tissues
      examined, with the highest levels in bone marrow. A non-expressed pseudogene also
      exists at chromosome 15q13-14. The new protein, which is most similar to the
      mitochondrial (M)-ABC1 protein, was also localized to mitochondria and therefore
      designated 'M-ABC2'. The N-terminus of M-ABC2 was shown to contain a
      mitochondrial-targeting signal sequence.

PMID- 10922476
TI  - Inhibition of inducible nitric oxide synthesis by oxidized lipoprotein(a) in a
      murine macrophage cell line.
AB  - Increased plasma levels of human lipoprotein(a) (Lp(a)) are highly correlated
      with the development of atherosclerotic lesions. During our study, we
      investigated the effects of native and hypochlorite oxidized lipoprotein(a) (ox
      Lp(a)) on nitric oxide production by the inducible nitric oxide synthase (iNOS)
      in lipopolysaccharide/interferon stimulated mouse macrophages (J774A.1). Ox-Lp(a)
      (0-2 microg/ml) induces a dose dependent inhibition of inducible nitric oxide
      synthesis. iNOS protein expression showed a dose dependent reduction as revealed
      by immunoblotting when cells were incubated with increasing amounts of ox-Lp(a).
      Ox-Lp(a) decreases iNOS mRNA synthesis as shown by reverse transcription
      polymerase chain reaction. Ox-Lp(a) induced iNOS inhibition might contribute to
      the development of atherosclerotic lesions by reducing the anti-atherogenic
      effects of nitric oxide.

PMID- 10922477
TI  - Differential inhibition of IL-6-type cytokine-induced STAT activation by PMA.
AB  - Prior activation of mitogen-activated protein kinases by phorbol 13-myristate 12
      acetate (PMA) results in an inhibition of interleukin (IL)-6-induced activation
      of the Janus kinase/signal transducer and activator of transcription (STAT)
      signaling pathway which is most likely mediated by the induction of suppressor of
      cytokine signaling-3 and requires the specific SHP2 binding site Y759 of the IL-6
      signal transducer gp130. In this study, we demonstrate that PMA inhibits STAT
      activation by IL-6 and the related cytokine leukemia inhibitory factor (LIF) but
      not by oncostatin M (OSM). Since the LIF receptor also contains an SHP2
      recruitment site whereas the OSM receptor lacks such a module, we propose that
      two SHP2 binding modules within a homo- or heterodimeric receptor are necessary
      to mediate the PMA inhibitory effect.

PMID- 10922478
TI  - Bgs2p, a 1,3-beta-glucan synthase subunit, is essential for maturation of
      ascospore wall in Schizosaccharomyces pombe.
AB  - Previously we have reported that Drc1p/Cps1p, a 1,3-beta-glucan synthase subunit,
      is essential for division septum assembly in Schizosaccharomyces pombe. In this
      report, we present evidence that S. pombe Bgs2p, a 1,3-beta-glucan synthase that
      shows 56% identity to Drc1p/Cps1p, is essential for maturation of ascospore wall
      in S. pombe, but is not required for vegetative growth. Diploid cells homozygous
      for the bgs2-null mutation, as well as homothallic bgs2-null mutant haploids
      undergo meiosis normally. However, a 1, 3-beta-glucan containing spore wall is
      not assembled in these cells. The spores resulting from meiosis of a bgs2-null
      mutant lyse upon release from the ascus and are therefore inviable. Using a green
      fluorescent protein-tagged Bgs2p, we demonstrate that Bgs2p is localized at the
      periphery of the ascospores during meiosis and sporulation. However, Bgs2p is not
      detected in vegetative cells. We conclude that Bgs2p is required for 1,3-beta
      glucan synthesis during ascospore wall maturation.

PMID- 10922480
TI  - Cholestan-3beta,5alpha,6beta-triol, but not 7-ketocholesterol, suppresses
      taurocholate-induced mucin secretion by cultured dog gallbladder epithelial
      cells.
AB  - In order to investigate oxysterol-mediated effects on the biliary system, we
      studied the effects of cholestan-3beta,5alpha,6beta-triol (TriolC) and 7
      ketocholesterol (7KC) on gallbladder epithelial cells. We compared their cell
      proliferation effects in cultured dog gallbladder epithelial cells (DGBE) to
      their effects in cultured human pulmonary artery endothelial cells (HPAE).
      Oxysterols inhibited cell proliferation in a dose-dependent fashion. Oxysterols
      inhibited cell growth to 50% of control at a higher dose for DGBE cells than for
      HPAE cells. TriolC was more cytotoxic than 7KC. We also investigated the effect
      of oxysterols on bile salt-induced mucin secretion by DGBE cells. TriolC
      suppressed mucin secretion by DGBE cells, whereas 7KC did not. These findings
      support the hypothesis that biliary oxysterols affect gallbladder mucosal
      function.

PMID- 10922479
TI  - Crosstalk between estrogen receptor alpha and the aryl hydrocarbon receptor in
      breast cancer cells involves unidirectional activation of proteasomes.
AB  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that
      activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine
      signaling pathways. T47D human breast cancer cells express a functional estrogen
      receptor alpha (ERalpha) and AhR, and treatment of these cells with 17beta
      estradiol (E2) or TCDD resulted in a rapid proteasome-dependent decrease in
      immunoreactive ERalpha and AhR proteins (>60-80%), respectively. E2 did not
      affect the AhR, whereas TCDD induced proteasome-dependent degradation of both the
      AhR and ERalpha in T47D and MCF-7 human breast cancer cells, and these responses
      were specifically blocked by proteasome inhibitors. Thus, TCDD-induced
      degradation of ERalpha may contribute to the antiestrogenic activity of AhR
      agonists and this pathway may be involved in AhR-mediated disruption of other
      endocrine responses.

PMID- 10922481
TI  - Enzyme kinetics of hevamine, a chitinase from the rubber tree Hevea brasiliensis.
AB  - The enzyme kinetics of hevamine, a chitinase from the rubber tree Hevea
      brasiliensis, were studied in detail with a new enzyme assay. In this assay, the
      enzyme reaction products were derivatized by reductive coupling to a chromophore.
      Products were separated by HPLC and the amount of product was calculated by peak
      integration. Penta-N-acetylglucosamine (penta-nag) and hexa-N-acetylglucosamine
      (hexa-nag) were used as substrates. Hexa-nag was more efficiently converted than
      penta-nag, which is an indication that hevamine has at least six sugar binding
      sites in the active site. Tetra-N-acetylglucosamine (tetra-nag) and allosamidin
      were tested as inhibitors. Allosamidin was found to be a competitive inhibitor
      with a K(i) of 3.1 microM. Under the conditions tested, tetra-nag did not inhibit
      hevamine.

PMID- 10922482
TI  - Characteristics and antifungal activity of a chitin binding protein from Ginkgo
      biloba.
AB  - An antifungal peptide from leaves of Ginkgo biloba, designated GAFP, has been
      isolated. Its molecular mass of 4244.0 Da was determined by mass spectrometry.
      The complete amino acid sequence was obtained from automated Edman degradation.
      GAFP exhibited antifungal activity towards Pellicularia sasakii Ito, Alternaria
      alternata (Fries) Keissler, Fusarium graminearum Schw. and Fusarium moniliforme.
      Its activities differed among various fungi. GAFP could also cause increased
      hyphal membrane permeabilization and a rapid alkalization of the medium when
      applied at 100 microgram/ml to Pellicularia sasakii Ito hyphae. The amino acid
      sequence of GAFP shows characteristics of the cysteine/glycine-rich chitin
      binding domain of many chitin binding proteins. The cysteine residues are well
      conserved.

PMID- 10922483
TI  - Interaction of wild-type and naturally occurring deleted variants of hepatitis B
      virus core polypeptides leads to formation of mosaic particles.
AB  - The simultaneous presence of hepatitis B virus (HBV) genomes carrying wild-type
      (wt) and in-frame deleted variants of the HBV core gene has been identified as a
      typical feature of HBV-infected renal transplant patients with severe liver
      disease. To investigate possible interactions of wt and deleted core polypeptides
      a two-vector Escherichia coli expression system ensuring their concomitant
      synthesis has been developed. Co-expression of wt and a mutant core lacking 17
      amino acid residues (77-93) within the immunodominant region led to the formation
      of mosaic particles, whereas the mutant alone was incapable of self-assembly.

PMID- 10922484
TI  - Magnetic field exposure enhances DNA repair through the induction of DnaK/J
      synthesis.
AB  - In contrast to the common impression that exposure to a magnetic field of low
      frequency causes mutations to organisms, we have demonstrated that a magnetic
      field can actually enhance the efficiency of DNA repair. Using Escherichia coli
      strain XL-1 Blue as the host and plasmid pUC8 that had been mutagenized by
      hydroxylamine as the vector for assessment, we found that bacterial transformants
      that had been exposed to a magnetic field of 50 Hz gave lower percentages of
      white colonies as compared to transformants that had not been exposed to the
      magnetic field. This result was indicative that the efficiency of DNA repair had
      been improved. The improvement was found to be mediated by the induced
      overproduction of heat shock proteins DnaK/J (Hsp70/40).

PMID- 10922485
TI  - Solution NMR structures of the polyene macrolide antibiotic filipin III.
AB  - The solution structure of filipin III, an antifungal polyene macrolide
      biosynthesized by Streptomyces filipinensis and widely used for the detection and
      the quantitation of cholesterol in biomembranes, has been calculated with a set
      of geometrical restraints derived from 1H NMR in DMSO-d(6) at 25 degrees C.
      Filipin III appears as a rod-shaped molecule of 18 A length. Its amphiphilic
      structure is made of an all-syn 1,3-polyol motif, stabilized by intramolecular
      hydrogen bonds on one side, and a conjugated pentaene moiety on the other side of
      the molecule. The overall shape is comparable to cholesterol, and the molecular
      structure of filipin III affords a first molecular basis to the comprehensive
      understanding of the interactions possible in the filipin III-cholesterol complex
      which is still unknown at the atomic resolution.

PMID- 10922486
TI  - The gene for hepatocyte nuclear factor (HNF)-4alpha is activated by
      glucocorticoids and glucagon, and repressed by insulin in rat liver.
AB  - The gene for a transcription factor hepatocyte nuclear factor-4alpha (HNF-4alpha)
      is responsible for maturity-onset diabetes of the young, type 1. We examined
      hormonal regulation of the HNF-4alpha gene in the liver. Stimulation of primary
      cultured rat hepatocytes with dexamethasone or glucagon led to induction of HNF
      4alpha mRNA, being antagonized by insulin. In the liver of streptozotocin-induced
      diabetic rat, mRNA and protein levels for HNF-4alpha were elevated, and were
      normalized by insulin treatment. Therefore, HNF-4alpha in the liver is likely to
      be involved in the regulation of glucose metabolism in response to these
      hormones.

PMID- 10922487
TI  - The initial pathogenesis of cadmium induced renal toxicity.
AB  - The novel application of magic angle spinning 1H NMR spectroscopy, coupled with
      pattern recognition techniques, has identified biochemical changes in lipid and
      glutamate metabolism that precede classical nephrotoxicity. These changes
      occurred in the bank vole (Clethrionomys glareolus) after chronic dosing, at a
      low level of exposure and at a renal Cd(2+) concentration (8.4 microgram/g dry
      wt) that was nearly two orders of magnitude below the WHO critical organ
      concentration (200 microg/g wet wt). These early stage effects of Cd(2+) on the
      biochemistry of renal tissue may reflect adaptation mechanisms to the toxic
      insult or the preliminary stages of the toxicological cascade.

PMID- 10922488
TI  - A fluorescent reporter gene as a marker for ventricular specification in ES
      derived cardiac cells.
AB  - We have established a CGR8 embryonic stem (ES) cell clone (MLC2ECFP) which
      expresses the enhanced cyan variant of Aequorea victoria green fluorescent
      protein (ECFP) under the transcriptional control of the ventricular myosin light
      chain 2 (MLC2v) promoter. Using epifluorescence imaging of vital embryoid bodies
      (EB) and reverse transcription-polymerase chain reaction (RT-PCR), we found that
      the MLC2v promoter is switched on as early as day 7 and is accompanied by
      formation of cell clusters featuring a bright ECFP blue fluorescence. The
      fluorescent areas within the EBs were all beating on day 8. MLC2ECFP ES cells
      showed the same time course of cardiac differentiation as mock ES cells as
      assessed by RT-PCR of genes encoding cardiac-specific transcription factors and
      contractile proteins. The MLC2v promoter conferred ventricular specificity to
      ECFP expression within the EB as revealed by MLC2v co-staining of ECFP
      fluorescent cells. MLC2ECFP-derived cardiac cells still undergo cell division on
      day 12 after isolation from EBs but withdraw from the cell cycle on day 16. This
      ES cell clone provides a powerful cell model to study the signalling roads of
      factors regulating cardiac cell proliferation and terminal differentiation with a
      view to using them for experimental cell therapy.

PMID- 10922489
TI  - Lysophosphatidic acid (LPA) receptors of the EDG family are differentially
      activated by LPA species. Structure-activity relationship of cloned LPA
      receptors.
AB  - We examined the structure-activity relationship of cloned lysophosphatidic acid
      (LPA) receptors (endothelial cell differentiation gene (EDG) 2, EDG4, and EDG7)
      by measuring [Ca(2+)](i) in Sf9 insect cells expressing each receptor using LPA
      with various acyl chains bound at either the sn-1 or the sn-2 position of the
      glycerol backbone. For EDG7 the highest reactivity was observed with LPA with
      Delta9-unsaturated fatty acid (oleic (18:1), linoleic (18:2), and linolenic
      (18:3)) at sn-2 followed by 2-palmitoleoyl (16:1) and 2-arachidonoyl (20:4) LPA.
      In contrast, EDG2 and EDG4 showed broad ligand specificities, although EDG2 and
      EDG4 discriminated between 14:0 (myristoyl) and 16:0 (palmitoyl), and 12:0
      (lauroyl) and 14:0 LPAs, respectively. EDG7 recognizes the cis double bond at the
      Delta9 position of octadecanoyl residues, since 2-elaidoyl (18:1, trans) and 2
      petroselinoyl (18:1, cis-Delta12) LPA were poor ligands for EDG7. In conclusion,
      the present study demonstrates that each LPA receptor can be activated
      differentially by the LPA species.

PMID- 10922490
TI  - Overexpression of T-type calcium channels in HEK-293 cells increases
      intracellular calcium without affecting cellular proliferation.
AB  - Increased expression of low voltage-activated, T-type Ca(2+) channels has been
      correlated with a variety of cellular events including cell proliferation and
      cell cycle kinetics. The recent cloning of three genes encoding T-type alpha(1)
      subunits, alpha(1G), alpha(1H) and alpha(1I), now allows direct assessment of
      their involvement in mediating cellular proliferation. By overexpressing the
      human alpha(1G) and alpha(1H) subunits in human embryonic kidney (HEK-293) cells,
      we describe here that, although T-type channels mediate increases in
      intracellular Ca(2+) concentrations, there is no significant change in
      bromodeoxyuridine incorporation and flow cytometric analysis. These results
      demonstrate that expressions of T-type Ca(2+) channels are not sufficient to
      modulate cellular proliferation of HEK-293 cells.

PMID- 10922491
TI  - Acylation of Galpha(13) is important for its interaction with thrombin receptor,
      transforming activity and actin stress fiber formation.
AB  - Palmitoylation of alpha-subunits in heterotrimeric G proteins has become a
      research object of growing attention. Following our recent report on the
      acylation of the mono-palmitoylated Galpha(12) [Ponimaskin et al., FEBS Lett. 429
      (1998) 370-374], we report here on the identification of three palmitoylation
      sites in the second member of the G(12) family, Galpha(13), and on the biological
      significance of fatty acids on the particular sites. Using mutants of alpha(13)
      in which the potentially palmitoylated cysteine residues (Cys) were replaced by
      serine residues, we find that Cys-14, Cys-18 and Cys-37 all serve as
      palmitoylation sites, and that the mutants lacking fatty acids are functionally
      defective. The following biological functions of Galpha(13) were found to be
      inhibited: coupling to the PAR1 thrombin receptor, cell transformation and actin
      stress fiber formation. Results from established assays for the above functions
      with a series of mutants, including derivatives of the constitutively active
      mutant Galpha(13)Q226L, revealed a graded inhibitory response on the above
      mentioned parameters. As a rule, it appears that palmitoylation of the N-proximal
      sites (e.g. Cys-14 and Cys-18) contributes more effectively to biological
      function than of the acylation site located more internally (Cys-37). However,
      the mutant with Cys-37 replaced by serine is more severely inhibited in stress
      fiber formation (80%) than in cell transformation (50%), pointing to the
      possibility of a differential involvement of the three palmitoylation sites in
      Galpha(13).

PMID- 10922492
TI  - Generation of both MHC class I- and class II-restricted antigenic peptides from
      exogenously added ovalbumin in murine phagosomes.
AB  - The phagosome fraction derived from a murine macrophage cell line (J774.1), which
      had internalized ovalbumin (OVA)-coated latex beads, was isolated. The peptides
      recovered from the phagosome fraction were separated on reverse phase HPLC and
      each fraction was analyzed for the content of either major histocompatibility
      complex (MHC) class I- or class II-restricted OVA-derived peptide. Both peptides
      were detected in the phagosome fraction after less than 15 min of
      internalization. It was also indicated that phagosomes degrade OVA protein into
      both MHC class I- and class II-restricted antigenic peptides by employing the
      same types of cathepsins. Furthermore, the results suggest that the MHC class I
      restricted peptide rapidly exits from the phagosome to the cytosol. These
      findings illustrate a potential role for phagosomes not only in MHC class II
      restricted but also in MHC class I-restricted exogenous antigen presentation
      pathways. Our results also point to the vital role of phagosomes in non-cytosolic
      antigen presentation pathway, in which further degradation of antigens by the
      proteasome is dispensable.

PMID- 10922493
TI  - Multiple sites of in vivo phosphorylation in the MDM2 oncoprotein cluster within
      two important functional domains.
AB  - The MDM2 oncoprotein is a negative regulatory partner of the p53 tumour
      suppressor. MDM2 mediates ubiquitination of p53 and targets the protein to the
      cytoplasm for 26S proteosome-dependent degradation. In this paper, we show that
      MDM2 is modified in cultured cells by multisite phosphorylation. Deletion
      analysis of MDM2 indicated that the sites of modification fall into two clusters
      which map respectively within the N-terminal region encompassing the p53 binding
      domain and nuclear export sequence, and the central acidic domain that mediates
      p14(ARF) binding, p53 ubiquitination and cytoplasmic shuttling. The data are
      consistent with potential regulation of MDM2 function by multisite
      phosphorylation.

PMID- 10922494
TI  - Identification of group X secretory phospholipase A(2) as a natural ligand for
      mouse phospholipase A(2) receptor.
AB  - Phospholipase A(2) receptor (PLA(2)R) mediates various biological responses
      elicited by group IB secretory phospholipase A(2) (sPLA(2)-IB). The recently
      cloned group X sPLA(2) (sPLA(2)-X) possesses several structural features
      characteristic of sPLA(2)-IB. Here, we detected a specific binding site of
      sPLA(2)-X in mouse osteoblastic MC3T3-E(1) cells. Cross-linking experiments
      demonstrated its molecular weight (180 kDa) to be similar to that of PLA(2)R. In
      fact, sPLA(2)-X was found to bind the recombinant PLA(2)R expressed in COS-7
      cells, and its specific binding detected in mouse lung membranes was abolished by
      the deficiency of PLA(2)R. These findings demonstrate sPLA(2)-X to be one of the
      high-affinity ligands for mouse PLA(2)R.

PMID- 10922495
TI  - Identification of a second site compensatory mutation in the Fe-protein that
      allows diazotrophic growth of Azotobacter vinelandii UW97.
AB  - Azotobacter vinelandii UW97 is defective in nitrogen fixation due to a
      replacement of serine at position 44 by phenylalanine in the Fe-protein [Pulakat,
      L., Hausman, B.S., Lei, S. and Gavini, N. (1996) J. Biol. Chem. 271, 1884-1889].
      Serine residue 44 is located in a conserved domain that links the nucleotide
      binding site and the MoFe-protein docking surface of the Fe-protein. Therefore,
      it is possible that the loss of function by A. vinelandii UW97-Fe-protein may be
      caused by global conformational disruption or disruption of the conformational
      change upon MgATP binding. To determine whether it is possible to generate a
      functional nitrogenase complex via a compensating second site mutation(s) in the
      Fe-protein, we have attempted to isolate genetic revertants of A. vinelandii UW97
      that can grow on nitrogen-free medium. One such revertant, designated A
      vinelandii BG9, encoded a Fe-protein that retained the Ser44Phe mutation and also
      had a second mutation that caused the replacement of a lysine at position 170 by
      glutamic acid. Lysine 170 is highly conserved and is located in a conserved
      region of the Fe-protein. This region is implicated in stabilizing the MgATP
      induced conformation of the Fe-protein and in docking to the MoFe-protein.
      Further complementation analysis showed that the Fe-protein mutant that retained
      serine 44 but contained the substitution of lysine at position 170 by glutamic
      acid was also non-functional. Thus, neither Ser44Phe nor Lys170Glu mutants of Fe
      protein were functional; however, the Fe-protein in A. vinelandii BG9 that
      contained both substitutions could support diazotrophic growth on the strain.

PMID- 10922496
TI  - Modelling flavin and substrate substituent effects on the activation barrier and
      rate of oxygen transfer by p-hydroxybenzoate hydroxylase.
AB  - The simulation of enzymatic reactions, using computer models, is becoming a
      powerful tool in the most fundamental challenge in biochemistry: to relate the
      catalytic activity of enzymes to their structure. In the present study, various
      computed parameters were correlated with the natural logarithm of experimental
      rate constants for the hydroxylation of various substrate derivatives catalysed
      by wild-type para-hydroxybenzoate hydroxylase (PHBH) as well as for the
      hydroxylation of the native substrate (p-hydroxybenzoate) by PHBH reconstituted
      with a series of 8-substituted flavins. The following relative parameters have
      been calculated and tested: (a) energy barriers from combined quantum
      mechanical/molecular mechanical (QM/MM) (AM1/CHARMM) reaction pathway
      calculations, (b) gas-phase reaction enthalpies (AM1) and (c) differences between
      the HOMO and LUMO energies of the isolated substrate and cofactor molecules (AM1
      and B3LYP/6-31+G(d)). The gas-phase approaches yielded good correlations, as long
      as similarly charged species are involved. The QM/MM approach resulted in a good
      correlation, even including differently charged species. This indicates that the
      QM/MM model accounts quite well for the solvation effects of the active site
      surroundings, which vary for differently charged species. The correlations
      obtained demonstrate quantitative structure activity relationships for an enzyme
      catalysed reaction including, for the first time, substitutions on both substrate
      and cofactor.

PMID- 10922497
TI  - Starvation-induced changes in the cell surface of Azospirillum lipoferum.
AB  - Three starvation regimes (a deficient culture medium, a saline buffer solution
      and distilled water) were evaluated for their possible effect on cell surface
      characteristics of Azospirillum lipoferum 1842 related to the initial adsorption
      of the bacterium to surfaces. The bacteria survived for 7 days in all media
      although they did not multiply. Upon transfer from a rich growth medium (nutrient
      agar) to starvation conditions, cell surface hydrophobicity dropped sharply but
      recovered its initial value within 24 to 48 h, except in phosphate-buffered
      saline, the length of the recovery period depending on the starvation medium.
      Starvation affected the sugar affinity of the A. lipoferum cell surface mainly
      towards p-aminophenyl-alpha-D-mannopyranoside, to a lesser extent to glucose, but
      not to other monosaccharides tested. Starvation changed the concentration of
      several cell surface proteins but did not induce the synthesis of new ones. The
      cell surface hydrophobic protein (43 kDa) of A. lipoferum 1842 was unaffected by
      any starvation treatment for a period of up to 48 h, but later disappeared. These
      data showed that starvation is not a major factor in inducing changes in the cell
      surface which lead to the primary phase of attachment of Azospirillum to
      surfaces.

PMID- 10922498
TI  - Simultaneous detection of the establishment of seed-inoculated Pseudomonas
      fluorescens strain DR54 and native soil bacteria on sugar beet root surfaces
      using fluorescence antibody and in situ hybridization techniques.
AB  - Colonization at sugar beet root surfaces by seedling-inoculated biocontrol strain
      Pseudomonas fluorescens DR54 and native soil bacteria was followed over a period
      of 3 weeks using a combination of immunofluorescence (DR54-targeting specific
      antibody) and fluorescence in situ hybridization (rRNA-targeting Eubacteria
      EUB338 probe) techniques with confocal laser scanning microscopy. The dual
      staining protocol allowed cellular activity (ribosomal number) to be recorded in
      both single cells and microcolonies of strain DR54 during establishment on the
      root. After 2 days, the population density of strain DR54 reached a constant
      level at the root basis. From this time, however, high cellular activity was only
      found in few bacteria located as single cells, whereas all microcolony-forming
      cells occurring in aggregates were still active. In contrast, a low density of
      strain DR54 was observed at the root tip, but here many of the bacteria located
      as single cells were active. The native population of soil bacteria, comprising a
      diverse assembly of morphologically different forms and size classes, initiated
      colonization at the root basis only after 2 days of incubation. Hence the dual
      staining protocol allowed direct microscopic studies of early root colonization
      by both inoculant and native soil bacteria, including their differentiation into
      active and non-active cells and into single or microcolony-forming cells.

PMID- 10922499
TI  - Response of a Pseudomonas aeruginosa biofilm community to DNA-damaging chemical
      agents.
AB  - Pseudomonas aeruginosa strain RM4440 carries a plasmid-borne fusion of the P.
      aeruginosa recA gene promoter to a promoterless lux operon from Vibrio fisheri.
      We tested the response of RM4440 in a biofilm to exposure to a 1-h pulse of each
      of 17 chemicals known to be toxic to bacteria and other organisms. The induction
      of light produced from the recA-lux fusion present in RM4440 proved to be
      sensitive and specific for DNA-damaging chemicals when included in a biofilm
      environment. This study demonstrates the potential usefulness of this construct
      for in situ investigation of bacterial communities.

PMID- 10922500
TI  - Detection of luciferase gene sequences in nonluminescent bacteria from the
      Chesapeake Bay.
AB  - A 745-bp luxA fragment was amplified from Vibrio harveyi (UM 1503), radiolabeled,
      and used as a probe to detect and quantify luxA genotypes in culturable bacterial
      populations from the Chesapeake Bay. DNA samples from 53 reference strains were
      also examined for this gene. The luxA-positive bacteria comprised from 0-6% of
      the culturable heterotrophic bacterial community in samples from the Bay. Only
      those reference strains known to be luminescent contained the luxA gene, as
      indicated by PCR. Results in all cases were confirmed by PCR of DNA extracts and
      Southern hybridization analyses, using an internal probe for confirmation of luxA
      amplification products. Sequence analysis of luxA genes from three nonluminescent
      bacteria isolated from the Chesapeake Bay indicated little or no differences when
      compared with luxA sequences from known marine luminescent bacterial species.
      These three Chesapeake Bay strains and other luxA-positive strains were tested
      with a luminometer and confirmed to be nonluminescent. All of over 7800 bacterial
      colonies enumerated during this study from Chesapeake Bay samples were non
      visibly luminescent. Our results indicate that luxA-positive bacteria isolated
      from the Chesapeake Bay are not generally luminescent on phenotypic examination,
      implying that gene probe techniques are required for examining luxA gene
      distribution in microbial populations present in environmental samples.

PMID- 10922501
TI  - Insecticidal toxin from Bacillus thuringiensis is released from roots of
      transgenic Bt corn in vitro and in situ.
AB  - The insecticidal toxin encoded by the cry1Ab gene from Bacillus thuringiensis was
      released in root exudates from transgenic Bt corn during 40 days of growth in
      soil amended to 0, 3, 6, 9, or 12% (v/v) with montmorillonite or kaolinite in a
      plant growth room and from plants grown to maturity in the field. The presence of
      the toxin in rhizosphere soil was determined by immunological and larvicidal
      assays. No toxin was detected in any soils from isogenic non-Bt corn or without
      plants. Persistence of the toxin was apparently the result of its binding on
      surface-active particles in the soils, which reduced the biodegradation of the
      toxin. The release of the toxin could enhance the control of insect pests or
      constitute a hazard to nontarget organisms, including the microbiota of soil, and
      increase the selection of toxin-resistant target insects.

PMID- 10922502
TI  - Establishment of introduced antagonistic bacteria in the rhizosphere of
      transgenic potatoes and their effect on the bacterial community.
AB  - In a field release experiment, rifampicin resistant mutants of two antagonistic
      plant-associated bacteria were used for seed tuber inoculation of transgenic T4
      lysozyme expressing potatoes, transgenic control potatoes and non-transgenic
      parental potatoes. The T4 lysozyme tolerant Pseudomonas putida QC14-3-8 was
      originally isolated from the tuber surface (geocaulosphere) of T4 lysozyme
      producing plants and showed in vitro antibacterial activity to the bacterial
      pathogen Erwinia carotovora ssp. atroseptica. The T4 lysozyme sensitive Serratia
      grimesii L16-3-3 was originally isolated from the rhizosphere of parental
      potatoes and showed in vitro antagonism toward the plant pathogenic fungus
      Verticillium dahliae. The establishment of the inoculated bacteria in the
      rhizosphere and geocaulosphere of the different plant lines was monitored over
      one growing season to assess the effect of T4 lysozyme produced by transgenic
      potato plants on the survival of both inoculants. Both introduced isolates were
      able to colonize the rhizo- and geocaulosphere of transgenic plants and non
      transgenic parental plants, and established in the rhizosphere at levels of ca.
      log(10) 5 colony forming units g(-1) fresh weight of root. During flowering of
      plants, significantly more colony counts of the T4 lysozyme tolerant P. putida
      were recovered from transgenic T4 lysozyme plants than from the transgenic
      control and the parental line. At this time, the highest level of T4 lysozyme (%
      of total soluble protein) was detected. Effects of the inoculants on the
      indigenous microbial community were monitored by analysis of PCR-amplified
      fragments of the 16S rRNA genes of the whole bacterial community after separation
      by denaturing gradient gel electrophoresis (DGGE). At any sampling time, the DGGE
      pattern of rhizosphere and geocaulosphere communities did not show differences
      between the inoculated and non-inoculated potatoes. Neither of the introduced
      strains became a dominant member of the bacterial community. This work was the
      first approach to assess the establishment of plant growth promoting
      rhizobacteria and potential biocontrol agents on transgenic plants.

PMID- 10922503
TI  - Spatial differences in bacterioplankton composition along the Catalan coast (NW
      Mediterranean) assessed by molecular fingerprinting.
AB  - Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified 16S rRNA gene
      fragments was used to compare surface bacterioplankton assemblages along the
      Catalan coast (NW Mediterranean). Samples from three coastal stations were
      compared with samples taken inside the Barcelona harbour and open sea samples
      taken during a cruise. The bacterial assemblage of each sample showed a
      characteristic and reproducible DGGE fingerprint. Between 17 and 35 bands were
      detected in each sample, and about 40% of the bands accounted for more than 80%
      of the band intensity in each sample. The presence of bands as well as their
      relative intensity was used to compare bacterial assemblages. Clear differences
      between the harbour samples and the coastal samples were evident during all
      periods. Marked temporal changes in the bacterial assemblages were detectable for
      the coastal sites, suggesting seasonal succession of coastal bacterioplankton.
      During each season, two stations presented a very similar bacterial composition
      (Barcelona and Masnou) whereas bacterial assemblages in Blanes were slightly
      different. These differences were consistent with the different hydrography of
      the area. Diversity indices calculated from DGGE fingerprints were relatively
      similar for all samples analysed, even though harbour samples were expected to
      present lower diversity values.

PMID- 10922504
TI  - Effects of heavy metals on nitrogen uptake by Paxillus involutus and mycorrhizal
      birch seedlings.
AB  - The effects of the heavy metals Cu, Cd, Ni, Pb and Zn on [(14)C]methylamine and
      [(14)C]aminoisobutyric acid uptake were studied in the free-living fungus
      Paxillus involutus and in mycorrhizal and non-mycorrhizal birch roots. The uptake
      of both N sources by P. involutus was inhibited by the five metals tested.
      However, Cu(2+) and Pb(2+) had a greater inhibitory effect. Non-competitive
      inhibitions were determined between heavy metals and [(14)C]methylamine uptake.
      [(14)C]Methylamine uptake was reduced by one third by 2 uM Cd(2+) and Cu(2+) in
      non-mycorrhizal roots, whereas that of mycorrhizal roots was not affected.
      However, it was reduced by 30 to 80% by 200 uM Cd(2+) and Cu(2+) irrespective of
      the mycorrhizal status. [(14)C]Aminoisobutyric acid uptake in mycorrhizal roots
      was not significantly affected by Cd(2+) and Cu(2+), whereas that of non
      mycorrhizal roots was decreased by 77% at 200 uM Cu(2+). [(14)C]Aminoisobutyric
      acid uptake was 4.5 to 6 fold higher in mycorrhizal roots, compared with non
      mycorrhizal roots, even under metal exposure. The high efficiency of N
      acquisition by mycorrhizal birch seedlings under metal exposure might be regarded
      as a mechanism of stress avoidance.

PMID- 10922505
TI  - Unravelling the genetic diversity of ruminal bacteria belonging to the CFB
      phylum.
AB  - Molecular biology approaches were employed to examine the genetic diversity of
      bacteria from the Cytophaga/Flexibacter/Bacteroides (CFB) phylum in the rumen of
      cattle. By this means we were able to identify cultured strains that represent
      some of the larger CFB clusters previously identified only by PCR amplification
      and sequencing. Complete 16S rDNA sequences were obtained for 16 previously
      isolated rumen strains, including the type strains of Prevotella ruminicola, P.
      bryantii, P. brevis and P. albensis to represent a wide range of diversity.
      Phylogenetic analysis of cultured strains revealed the existence of three
      clusters of ruminal CFB: (i) a cluster of Prevotella strains, which have been
      found only in the rumen, including the two type strains, P. brevis GA33(T) and P.
      ruminicola 23(T); (ii) Prevotella spp. that cluster with prevotellas from other
      ecological niches such as the oral cavity and which include the type strains, P.
      bryantii B(1)4(T) and P. albensis M384(T); (iii) two Bacteroides spp. strains
      clustering with B. forsythus of oral origin. In order to establish whether the
      cultivated isolates cover the whole range of ruminal CFB genetic diversity, 16S
      rRNA gene sequences were amplified and cloned from DNA extracted from the same
      rumen samples (one cow in Slovenia, one in Scotland and three in Japan).
      Sequencing and phylogenetic analysis of 16S rRNA genes confirmed the existence of
      two superclusters of ruminal Prevotella, one exclusively ruminal and the other
      including non-ruminal species. In the case of ruminal Bacteroides spp., however,
      phylogenetic analysis revealed the existence of three new superclusters, one of
      which has as yet no cultivable counterpart. Interestingly, these Bacteroides
      clusters were represented almost exclusively by clone libraries from the Japanese
      cattle and only three sequences were from the European cattle. This study agrees
      with previous analyses in showing that rumen Prevotella/Bacteroides strains
      exhibit a remarkable degree of genetic diversity and suggests that different
      strain groupings may differ greatly in their recovery by cultural methods. The
      most important conclusion, however, is that cultured strains can be identified
      that represent some of the larger clusters previously identified only by PCR
      amplification and sequencing.

PMID- 10922506
TI  - Comment to Sherr and Sherr (1999): "Is there any appropriate way to distinguish
      different beta-N-acetylhexosaminidase activities in aquatic environments?"
AB  - The recent paper of Sherr and Sherr on detecting low-affinity beta
      glucosaminidase activity in several marine microbes extends current knowledge
      about hydrolytic enzyme activities in natural aquatic systems. However, their
      conclusions regarding the whole-cell assay with MUF-N-acetyl-beta-D-glucosaminide
      (MUF-[GlcNAc]) cannot be accepted. First, we explicitly demonstrate a strong
      correlation between extracellular activities of the high-affinity enzymes and
      grazing rates of bacterivorous protists. Therefore, the assay can still be
      recommended for the estimation of total protistan grazing on prokaryotic
      picoplankton. Second, the ability of many aquatic organisms to produce enzymes
      which cleave fluorogenic substrates, such as MUF-[GlcNAc] and/or MUF-beta-D
      N,N',N"-triacetylchitotriose (MUF-[GlcNAc](3)), has been well-documented during
      the last decade. Thus, neither of the two substrates may be considered as
      exclusively specific for targeting either lysozymes or beta-N
      acetylhexosaminidases.

PMID- 10922507
TI  - Reply to the comment of J. Vrba: Problems with enzyme-based methods.

PMID- 10922509
TI  - Connections underlying the synthesis of cognition, memory, and emotion in primate
      prefrontal cortices.
AB  - Distinct domains of the prefrontal cortex in primates have a set of connections
      suggesting that they have different roles in cognition, memory, and emotion.
      Caudal lateral prefrontal areas (areas 8 and 46) receive projections from
      cortices representing early stages in visual or auditory processing, and from
      intraparietal and posterior cingulate areas associated with oculomotor guidance
      and attentional processes. Cortical input to areas 46 and 8 is complemented by
      projections from the thalamic multiform and parvicellular sectors of the
      mediodorsal nucleus associated with oculomotor functions and working memory. In
      contrast, caudal orbitofrontal areas receive diverse input from cortices
      representing late stages of processing within every unimodal sensory cortical
      system. In addition, orbitofrontal and caudal medial (limbic) prefrontal cortices
      receive robust projections from the amygdala, associated with emotional memory,
      and from medial temporal and thalamic structures associated with long-term
      memory. Prefrontal cortices are linked with motor control structures related to
      their specific roles in central executive functions. Caudal lateral prefrontal
      areas project to brainstem oculomotor structures, and are connected with premotor
      cortices effecting head, limb and body movements. In contrast, medial prefrontal
      and orbitofrontal limbic cortices project to hypothalamic visceromotor centers
      for the expression of emotions. Lateral, orbitofrontal, and medial prefrontal
      cortices are robustly interconnected, suggesting that they participate in concert
      in central executive functions. Prefrontal limbic cortices issue widespread
      projections through their deep layers and terminate in the upper layers of
      lateral (eulaminate) cortices, suggesting a predominant role in feedback
      communication. In contrast, when lateral prefrontal cortices communicate with
      limbic areas they issue projections from their upper layers and their axons
      terminate in the deep layers, suggesting a role in feedforward communication.
      Through their widespread connections, prefrontal limbic cortices may exercise a
      tonic influence on lateral prefrontal cortices, inextricably linking areas
      associated with cognitive and emotional processes. The integration of cognitive,
      mnemonic and emotional processes is likely to be disrupted in psychiatric and
      neurodegenerative diseases which preferentially affect limbic cortices and
      consequently disconnect major feedback pathways to the neuraxis.

PMID- 10922508
TI  - Intrinsic excitatory connections in the prefrontal cortex and the pathophysiology
      of schizophrenia.
AB  - Working memory, a fundamental cognitive process that is disturbed in
      schizophrenia, appears to depend upon the sustained activity of specific
      populations of neurons in the prefrontal cortex. Understanding the neural
      mechanism(s) that may contribute to the sustained activity of these neurons
      represents a critical step in predicting the types of alterations in prefrontal
      circuitry that may be present in schizophrenia, and in determining how such
      alterations may contribute to the cognitive symptoms of this disorder. This
      article reviews recent findings which suggest that intrinsic horizontal
      connections among pyramidal neurons in layer 3 of the dorsolateral prefrontal
      cortex may provide a critical anatomical substrate for working memory processes,
      and that alterations in these connections may account for the observations of
      disturbed working memory, adolescence-related onset of clinical features, and
      certain pathological changes in the prefrontal cortex of subjects with
      schizophrenia.

PMID- 10922510
TI  - Prefrontal neurons in networks of executive memory.
AB  - The neuronal networks of the frontal lobe that represent motor or executive
      memories are probably the same networks that cooperate with other cerebral
      structures in the temporal organization of behavior. The prefrontal cortex, at
      the top of the perception-action cycle, plays a critical role in the mediation of
      contingencies of action across time, an essential aspect of temporal
      organization. That role of cross-temporal mediation is based on the interplay of
      two short-term cognitive functions: one retrospective, of short-term active
      perceptual memory, and the other prospective, of attentive set (or active motor
      memory). Both appear represented in the neuronal populations of dorsolateral
      prefrontal cortex. At least one of the mechanisms for the retention of active
      memory of either kind seems to be the reentry of excitability through recurrent
      cortical circuits. With those two complementary and temporally symmetrical
      cognitive functions of active memory for the sensory past and for the motor
      future, the prefrontal cortex seems to secure the temporal closure at the top of
      the perception-action cycle.

PMID- 10922512
TI  - Expression of Ca(2+)-binding protein regucalcin in rat brain neurons: inhibitory
      effect on protein phosphatase activity.
AB  - The expression of Ca(2+)-binding protein regucalcin and its role in the
      regulation of protein phosphatase activity in rat brain neuronal cells obtained
      with primary culture was investigated. The expression of regucalcin mRNA was
      demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis
      in brain neuronal cells using rat regucalcin-specific primers. Moreover,
      regucalcin protein in brain neuronal cells was detected by Western blot analysis
      using a polyclonal rabbit anti-regucalcin antibody. The presence of anti
      regucalcin monoclonal antibody (20 or 50 ng/ml) in the enzyme reaction mixture
      caused a significant increase in protein phosphatase activity toward
      phosphotyrosine, phosphoserine and phosphothreonine in the reaction mixture
      containing the cytosol of neuronal cell homogenates. This increase was completely
      prevented by the addition of regucalcin (10(-8) M). Protein phosphatase activity
      toward three phosphoaminoacids was significantly elevated by the addition of
      Ca(2+) (100 microM) and calmodulin (5 microg/ml). This elevation was completely
      blocked by the addition of regucalcin (10(-8) M). The present study demonstrates
      that regucalcin is expressed in rat brain neuronal cells, and that it has an
      inhibitory effect on protein phosphatase activity in the cells.

PMID- 10922513
TI  - Vestibular-induced behaviour of rats born and raised in hypergravity.
AB  - One group of rats were bred and kept under hypergravity (HG) conditions (2.5 g)
      in a centrifuge. Another group were bred and kept under normal gravity conditions
      (1 g). Rats from both groups were dropped from a supine position into a water
      basin under infrared illumination leaving only gravity (1 g for both groups) for
      orientation. The airrighting reflex and reappearance at the water surface were
      examined. The success rate for airrighting of HG rats is 47% versus 45% for
      controls, and is performed about equally fast by both groups. The success rate of
      HG and control hamsters is </=25% and >/=80%, respectively [22]. This
      interspecific difference does not appear to support the conjecture that altered
      behaviour is caused by a structural change of vestibular end organs during
      ontogenetic development under HG. The success rate for surfacing of control rats
      is 100%. Surfacing of young HG rats is less successful (36% at age 6 weeks) and
      requires more time. On average, surfacing of adult rats of both groups is about
      the same. Apparently, the repeated stay of centrifuge-bred rats at 1 g for
      experiments and daily care suffices to recalibrate and improve their orientation,
      which is essential for surfacing.

PMID- 10922511
TI  - Treadmill exercise training augments brain norepinephrine response to familiar
      and novel stress.
AB  - In a test of hypothalamic-pituitary-adrenal (HPA) cortical and hypothalamic
      pituitary-gonadal (HPG) interaction during familiar and novel stress, we
      previously reported that treadmill exercise training led to blunted plasma
      adrenocorticotrophin (ACTH) response to acute treadmill running but a hyper
      responsiveness of ACTH after novel immobilization. In this follow-up analysis, we
      examined whether those results might be plausibly explained by a similar effect
      of treadmill exercise training on increased levels of norepinephrine (NE) in
      hypothalamic and limbic brain regions which synergize to modulate the release of
      ACTH during stress. Ovariectomized Sprague-Dawley rats that had been exercise
      trained by treadmill running or remained sedentary for 6 weeks received
      intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3
      days prior to 15 min of familiar treadmill running or novel immobilization.
      Treadmill exercise training, regardless of Eb treatment or type of stress,
      increased NE levels in the paraventricular (PVN), arcuate, medial preoptic, and
      ventromedial areas of the hypothalamus and protected against depletion of NE in
      the locus coeruleus, amygdala, and hippocampus. We conclude that treadmill
      exercise training has a hyperadrenergic effect in brain areas that modulate
      hypothalamic regulation of ACTH release during stress that is independent of HPA
      HPG interaction and novelty of the stressor. To help elucidate these findings,
      the effects of treadmill exercise training on A1-A2 nuclei which innervate the
      PVN and their relationship with the limbic and hypothalamic responses we report
      require study.

PMID- 10922514
TI  - Hippocampal gamma-aminobutyric acid transporter alterations following focal
      epileptogenesis induced in rat amygdala.
AB  - To study the role of hippocampal gamma-aminobutyric acid (GABA) transporters in
      epileptogenesis, we induced chronic seizures by ferric cation injection into the
      rat amygdaloid body. We used western blotting to measure alterations in the
      expression of hippocampal GABA transporter proteins GAT-1 and GAT-3. GAT-1
      increased bilaterally (from 150 to 250%) at 5 to 15 days after injection, but
      returned to control levels by 30 days. In contrast, GAT-3 also significantly
      increased bilaterally at 5 days and 15 days, but remained elevated bilaterally at
      30 days after injection. Alterations in GAT-1 levels are apparently transient
      responses to seizure activity that occur during the acute phase of
      epileptogenesis. However, we propose that regulation of the GAT-3 subtype
      transporter was chronically elevated (at least 30 days), represents an effect of
      epileptogenesis induced by ferric ion injected into the amygdaloid body.

PMID- 10922515
TI  - A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine
      and its metabolites in the brains of opioid-dependent rats.
AB  - The influence of an inhibitor of cAMP-dependent protein kinase and protein kinase
      C, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], on naloxone (an opioid
      receptor antagonist)-precipitated withdrawal signs and changes in levels of
      dopamine (DA) and its metabolites in morphine- or butorphanol-dependent rats was
      investigated. Animals were infused continuously with morphine (a mu-opioid
      receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor agonist)
      for 3 days. Naloxone precipitated withdrawal syndrome and decreased the levels of
      DA in the cortex, striatum, and midbrain; 3, 4-dihydroxyphenylacetic acid (DOPAC)
      in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA)
      in the striatum, limbic areas, and midbrain regions. In animals rendered
      dependent on butorphanol, the results obtained were similar to those of morphine
      dependent rats except for the changes in DOPAC levels. Concomitant infusion of H
      7 and opioid blocked both the expression of withdrawal signs and the decreases in
      DA, DOPAC, and HVA levels in a dose-dependent manner. These results suggest that
      the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity
      accompanying the increase of DA neuron activity during continuous infusion of
      opioids leads to an abrupt reduction in levels of DA and its metabolites
      precipitated by naloxone, which is intimately involved in the expression of
      physical dependence on opioids.

PMID- 10922516
TI  - Increase in vulnerability of middle-aged rat brain to lead by cerebral energy
      depletion.
AB  - The neurotoxic effects of low-level lead (Pb) during senescence are increasing
      interests of importance. We investigated the effects of low-level Pb on the brain
      in a normal condition and a pathophysiological condition of energy shortage that
      is commonly found in age-related neurological diseases. Middle-aged rats (15
      months old) were exposed to 200 mg/l Pb acetate in drinking water for 2 months
      and thereafter received bilateral intracerebroventricular injections of
      streptozotocin (STZ). After 1 month's additional exposure to the same level of Pb
      solution as before the rats were sacrificed. Blood and brain Pb levels were
      measured by graphite furnace atomic absorption spectrophotometry. Energy-rich
      phosphate levels in the brain were determined by high-performance liquid
      chromatography equipped with a UV detector. Astroglial activation and glucose
      regulated protein (GRP)94 expression were examined immunohistochemically.
      Exposure to Pb increased the blood Pb level to 10.8 microg/dl and the brain Pb
      level to 0.052 microg/g. But a significant additional increase in the brain Pb
      level, to 0.101 microg/g, became obvious in rats treated with Pb + STZ. Both Pb
      and STZ induced perturbation in brain energy metabolism, but no further
      alteration in energy metabolite levels was found in rats treated with Pb + STZ.
      Astroglial activation and GRP94-positive astrocytes and neurons were found only
      in the brains of Pb + STZ-treated rats. These results suggest that exposure to
      low-level Pb can perturb brain energy metabolism and the brain becomes more
      vulnerable to Pb when it is under energy stress.

PMID- 10922517
TI  - Fos expression and 2-deoxyglucose uptake following seizures in developing
      genetically epilepsy-prone rats.
AB  - Juvenile genetically epilepsy-prone rats (GEPR)-3s display one of three types of
      seizures in response to sound: a typical class 3 seizure consisting of an
      explosive running/bouncing episode followed by a clonic seizure (audiogenic
      response score, ARS-3); an ARS-3 seizure followed by a forebrain seizure that
      includes facial and forelimb (F&F) clonus with rearing (ARS-3f); or, a
      running/bouncing episode followed by a severe tonic seizure with complete
      hindlimb extension (ARS-9) not accompanied with subsequent F&F clonus. The adult
      seizure phenotype, manifest in all GEPR-3s by age 45 days of age, consists of an
      ARS-3 not followed by F&F clonus or tonic extension. The present studies sought
      to determine the neuronal networks activated during these various developmental
      convulsive patterns by examining anatomical patterns of [(14)C]2-deoxyglucose (2
      DG) uptake or immediate-early-gene (Fos) expression subsequent to seizures. Many,
      but not all, brain areas of control rats showed age-related increases in Fos
      expression in response to the acoustic stimulation. An age effect was not
      observed in 2-DG uptake. In GEPRs, the profiles of Fos expression and 2-DG uptake
      following seizures were often parallel; however, there were notable exceptions.
      For example, increased 2-DG uptake in the cochlear nuclei, central region of the
      inferior colliculi, and the substantia nigra were not accompanied by increased
      Fos expression in these areas regardless of the seizure phenotypes. Reciprocally,
      other regions, particularly in the amygdala, ventromedial hypothalamus and
      parabrachial areas, displayed intense seizure related Fos labeling without
      detectable increases in 2-DG uptake. Fos and 2-DG uptake patterns in response to
      acoustic stimulation varied according to brain region, seizure phenotype and
      severity. In general, the degree of 2-DG uptake correlated with seizure severity.
      For example, the ARS-9 seizures, being the most intense, resulted in significant
      increases in 2-DG uptake in almost all brain regions examined. 2-DG uptake
      following the ARS-3f and ARS-3 seizures, although increased, did not reach
      statistical significance in most brain areas. In contrast to the 2-DG findings, a
      seizure-severity dependent effect was not seen with Fos. Rather, the induction of
      Fos associated with acoustic stimulation and seizure was more associated with age
      and seizure-phenotype. Thus, the developmental profiles of Fos expression and 2
      DG uptake in response to seizures are distinctly different and concurrent
      examination of both markers is useful in the identification of brain circuitry
      involved in seizure development.

PMID- 10922518
TI  - Inhibition of microglial cell activation by cortisol.
AB  - Cortisol is a steroid hormone produced in response to stress. This glucocorticoid
      can be toxic to neurons, and thus may be important in neurodegenerative diseases
      including Alzheimer's disease. Activated microglia produce molecules including
      nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) which can also be
      toxic to neurons. The current study was designed to determine the effect of
      cortisol upon the activation of primary cultured microglia and transformed N9
      microglial cells. The studies indicate that cortisol represses lipopolysaccharide
      (LPS) induction of nitric oxide production in these microglial cells. The hormone
      acts by inhibiting the production of inducible nitric oxide synthase (iNOS) which
      catalyses the synthesis of NO. Cortisol likely acts by blocking transcription of
      iNOS gene expression since the hormone represses LPS induction of iNOS RNA levels
      in these cells. Activated microglia produce increased TNF-alpha, in addition to
      increased NO. The current studies demonstrate that cortisol inhibits release of
      TNF-alpha from LPS-treated microglial cells. Collectively, these data suggest
      that although cortisol may be directly toxic to neurons, the hormone may
      indirectly protect neurons by blocking the production of cytotoxic molecules by
      microglia.

PMID- 10922519
TI  - Distribution of GABA(B) receptor protein in somatosensory cortex and thalamus of
      adult rats and during postnatal development.
AB  - In the present study we report the immunolocalisation of gamma-aminobutyric acid
      (GABA)(B) receptors within the cerebral somatosensory cortex (S1) and thalamus of
      adult and young (1-22 postnatal days) rats. The antibody used recognises a
      peptide in the carboxy-terminal domain and therefore did not distinguish between
      the different isoforms GABA(B)1a or GABA(B)1b. The results showed that GABA(B)
      receptor protein was widely distributed in the brain of both adult and young
      rats, with different degrees of labelling in separate cerebral nuclei. Antibody
      labelling was localised both on cells and the neuropil. In the cerebral cortex of
      adult animals the highest immunolabelling was evident in layers V and VIb,
      although immunoreactivity was also present in the superficial layers. The
      strongest signal was evident in the medial habenula.The thalamus showed labelling
      in the reticular, ventrobasal and geniculate nuclei. In the first postnatal days
      GABA(B) expression was evident in the cortical cells of layer V, VIb and in the
      cortical plate. The pattern of labelling in the cerebral cortex of young rats
      became indistinguishable from that of adult rats by day 12. In the thalamus, the
      main difference compared to the adult pattern was observed in the mediodorsal
      nucleus which, in early development, showed a high immunosignal, however, by
      postnatal day 22 the immunoreactivity decreased with only some scattered cells
      labelled in the adult brain.

PMID- 10922520
TI  - Repeated cocaine treatment alters tyrosine hydroxylase in the rat nucleus
      accumbens.
AB  - To determine whether repeated exposure of cocaine affects the dopaminergic
      innervation of the nucleus accumbens, we employed a typical cocaine-dosing
      regimen in adult male Sprague-Dawley rats followed by an immunocytochemical
      analysis of tyrosine hydroxylase (TH). Treatment consisted of bi-daily injections
      of saline or 15 mg/kg cocaine for 5 consecutive days. After 2 or 14 days of
      withdrawal, sections of the nucleus accumbens (NAc) were processed for tyrosine
      hydroxylase and the number of immunoreactive varicosities in the core and shell
      were quantified. Two days after treatment, the core demonstrated a decrease,
      while after 14 days of treatment, the shell was found to contain significantly
      more TH immunoreactive varicosities. Additionally, 2 days post-cocaine treatment,
      core-shell differences were found, however moderate differences were also found
      in the saline treatment group, making the absolute effects of cocaine difficult
      to separate from injection and handling effects at this time point. These results
      suggest that the shell of the NAc may undergo alterations that could be involved
      with behavioral sensitization that typically results from such cocaine treatment
      regimens.

PMID- 10922521
TI  - Electrical stimulation of the midbrain tectum enhances dopamine release in the
      frontal cortex.
AB  - One widely used animal model of anxiety is the electrical stimulation of a given
      structure supposed to be involved in the neural circuitry underlying emotional
      behavior. Indeed, electrical stimulation of midbrain structures with substrates
      for the processing of fear-like responses, such as the dorsal periaqueductal gray
      matter (DPAG) or the inferior colliculus (IC), produces behavioral, sensorial and
      autonomic responses very similar to the defense reactions observed in
      environmental threatening situations. It has also been proposed that the required
      level of integration of all these components of the defense reaction needs an
      integrative process situated at higher brain level, as the prefrontal cortex. As
      a matter of fact, substantial cortical inputs to the midbrain tectum have already
      been found. In view of this evidence, it seems important to know whether animals
      stimulated in the midbrain tectum would present neurochemical changes in the
      prefrontal cortex. To this end, we examined the temporal course of the effects of
      the electrical stimulation of the DPAG and IC on the dopamine (DA) release in the
      prefrontal cortex. Electrical stimulation of these structures was performed at
      the alertness (control) and escape thresholds. Electrical stimulation of the
      inferior colliculus at the escape threshold produced a long-lasting increase in
      the levels of corticofrontal dopamine in relation to these measurements in the
      control group. No significant changes in extracellular DA release in this
      cortical area could be observed following DPAG electrical stimulation. These
      findings bring evidence for the involvement of dopamine of the frontal cortex in
      the setting up of adaptive responses to stressful situations generated at the
      inferior colliculus level.

PMID- 10922522
TI  - Differential effects of parafascicular electrical stimulation on active avoidance
      depending on the retention time, in rats.
AB  - To evaluate whether electrical stimulation of the parafascicular nucleus of the
      thalamus can improve short-term (24 h) and/or long-term (11 days) retention of
      two-way active avoidance, rats were implanted with an electrode at this nucleus
      (experimental groups with stimulation in the parafascicular, and control groups
      without stimulation) or above it (other control groups without stimulation).
      After a single 30-trial acquisition session, experimental groups were submitted
      to a 20-min session of electrical stimulation. Results showed that parafascicular
      stimulation improved the 24-h retention of the task (number of avoidances made),
      increasing also the percentage of subjects that achieved a learning criterion and
      reducing the number of trials needed to reach it. In contrast, no differences
      among groups were found on the 11-day retention test. The present results agree
      with previous data showing a short-term effect of parafascicular stimulation on
      retention, and confirm its involvement in learning and memory modulation. These
      data are discussed in the context of the acceleration and strengthening of the
      memory by activation of arousal systems, and/or specific cortical-striatal
      systems.

PMID- 10922523
TI  - Ketamine blockage of both tetrodotoxin (TTX)-sensitive and TTX-resistant sodium
      channels of rat dorsal root ganglion neurons.
AB  - Ketamine, a general anesthetic, has been reported to block sodium channels. Two
      types of Na(+) channels, tetrodotoxin (TTX)-sensitive (TTX-s) and TTX-resistant
      (TTX-r), are expressed in dorsal root ganglion (DRG) neurons. The present study
      was to investigate the effects of ketamine on both types, particularly on TTX-r
      channels, using whole-cell patch-clamp recordings in dissociated rat DRG neurons.
      In addition to confirming ketamine-induced blockage of TTX-s Na(+) current, we
      showed for the first time that ketamine blocked TTX-r Na(+) channels on small DRG
      neurons in dose-dependent and use-dependent manner. Half-maximal inhibitory
      concentration (IC(50)) was 866.2 microM for TTX-r Na(+) channels. TTX-r Na(+)
      channels were more sensitive to ketamine in inactivated state (IC(50) = 314.8
      microM) than in resting state (IC(50) = 866.2 microM). IC(50) was 146.7 microM
      for TTX-s Na(+) current. Activation and inactivation properties of both TTX-s and
      TTX-r Na(+) channels were affected by ketamine. Since TTX-r Na(+) channels were
      preferentially expressed in small DRG neurons known as nociceptors, blockage of
      TTX-r Na(+) channels by ketamine may result in reducing nociceptive signals
      conducting to the spinal cord. Moreover, both TTX-r and TTX-s Na(+) channels
      would be non-selectively blocked by ketamine at high concentration, suggesting
      that the high dose of ketamine might produce an action of local anesthesia.

PMID- 10922525
TI  - Early-session increases in responding during extinction.
AB  - After training under a variable-interval 60-s schedule of reinforcement, four
      rats were exposed to 30-min extinction tests, which occurred either at the start
      or at the end of the session (each session being 50-min long). Response rate in
      extinction decreased when the extinction test occurred at the end of the session,
      but first increased and then decreased when the extinction test occurred at the
      start of the session. Consistent with other recent results, this finding suggests
      that some variable, other than reinforcement, contributes to early-session
      increases in responding.

PMID- 10922524
TI  - Differential effects of colchicine on the induction of nitric oxide synthase in
      neurons containing progesterone receptors of the guinea pig hypothalamus.
AB  - Using nicotinamide-adenine-dinucleotide-phosphate-diaphorase (NADPHd)
      histochemistry, we analyzed the effects of an intracerebroventricular injection
      of colchicine on the activity of neuronal nitric oxide synthase in the
      hypothalamic nuclei of intact and ovariectomized estradiol-primed guinea pigs. We
      also examined the effects of colchicine on the immunocytochemical colocalization
      of nitric oxide synthase with the progesterone receptor in the ventrolateral
      nucleus, a key region in the control of sexual behavior. Treatment with
      colchicine resulted in a significant increase in the number of NADPHd-positive
      neurons in the ventrolateral nucleus in intact as well as in ovariectomized
      estradiol-primed animals, whereas in the other hypothalamic regions analyzed
      (preoptic area, paraventricular nucleus and posterior arcuate nucleus), the
      enzymatic activity remained unchanged. Quantitative analysis showed a
      significantly greater number of NADPHd-positive cells in the medial and the
      posterior aspects of the ventrolateral nucleus of colchicine-treated guinea pigs
      compared to the control group. In the caudal subdivision of this nucleus,
      colchicine induced nitric oxide synthase in the target cells for progesterone.
      These results suggest that neuronal nitric oxide synthase activity in the
      hypothalamus is affected by colchicine in a region-specific manner and especially
      in the ventrolateral nucleus, which is involved in progesterone-facilitated
      lordosis.

PMID- 10922526
TI  - Grazing behaviour of sheep in a situation of conflict between feeding and social
      motivations.
AB  - We investigated how food preferences and social bonds interact to determine the
      choice of grazing location in sheep. Ewes of INRA 401 breed were grazed in plots
      in which taller areas, i.e. preferred feeding sites, were left to grow at 15 or
      50 m from a socially attractive site, i.e. familiar ewes placed in a public pen
      at one end of the plot. Eight experimental ewes were tested either alone or in
      groups with one, three or six accompanying animals chosen amongst 20 other
      familiar ewes. We used a Latin square design, in which the eight treatments (two
      distancesxfour group sizes) were balanced in 8 measurement days. We recorded, in
      20-min tests, the behaviour of the experimental ewes by focal sampling, and the
      location of each animal in the groups by scan sampling. Foraging location,
      dietary choices and vigilance behaviour of ewes were affected by both the
      distance between the group of public peers and the preferred feeding site, and
      the size of their own group. Our results suggest that a sheep will move whether
      alone or with a few peers to a preferred feeding site located close to the core
      of its social group. In a small sub-group, its frequency of vigilance behaviour
      increases, probably to maintain social contact with the rest of the group.
      Conversely, a sheep will not leave its group to reach a preferred feeding site
      located further away unless it is followed by several other peers.

PMID- 10922527
TI  - Changes in exploration from courtship to the breeding state in red-rumped parrots
      (Psephotus haematonotus).
AB  - Animals explore their environment to gather information about feeding areas,
      resting places, or suitable territories for reproduction. During the annual cycle
      seasonal variation in exploration occurs at least in some species. In this study,
      exploratory behaviour of red-rumped parrots (Psephotus haematonotus) was
      investigated during part of the reproductive period including courtship and
      incubation. On 2 test days 14 pairs in either the courtship or the breeding state
      were confronted with three unknown objects in their familiar aviary for 6 h on
      each of 2 days. Test days were separated by a 2-day pause. Exploration by the
      males did not change from courtship to breeding, whereas in females latency to
      first contact increased, and duration of exploration and the number of objects
      touched decreased from courtship to breeding state. Considering the pair as a
      unit, the total duration of exploration was shorter in breeding pairs than in
      pairs during courtship. Changes in exploration from the first to the second day
      of object exposure occurred in both sexes. Males explored longer on the second
      day, females contacted the objects significantly later on the second day but
      showed no significant changes in duration of exploration. The changes in
      exploration might be due to changed cost/benefit considerations during courtship
      and breeding.

PMID- 10922528
TI  - Delayed matching to sample: the effects of sample-set size on human performance.
AB  - The discriminative performance of students was assessed on a delayed-matching-to
      sample task (DMST) using disks, presented by a computer, as stimuli. The size of
      the non-matching comparison stimuli was changed, for each participant, until each
      was 100% correct at 0.05 s delay. Then delays of 0.05, 2, 4, 8 and 16 s were
      paired with each of one, four, eight, 16, and 32 sample stimuli. Accuracy
      generally decreased over the one, four and eight samples, did not change
      consistently over the largest sample-set sizes and decreased as delay increased.
      Both delay and sample-set size had statistically significant main effects, their
      interaction was not significant. Fitted exponential functions gave a measure of
      discrimination at zero delay, a, and a measure of the rate of decrement in
      performance with increasing delay, b. As number of sample stimuli increased there
      was no systematic change in b, while a decreased most over one to four samples,
      decreased less with eight samples, and decreased least from 16 to 32 samples.
      These results suggest that the effects of varying sample-set size depends on the
      range of sizes studied, thus, they provide a possible explanation for some
      previous disparate findings. They also suggest that it might be proactive
      interference that leads to decreases in accuracy with increasing sample-set size.

PMID- 10922529
TI  - Chronic mild stress alleviates anxious behaviour in female mice in two
      situations.
AB  - Chronic mild stress (CMS) alleviates anxious behaviour in rats in an elevated
      plus-maze. In the present study this finding has been extended in mice to the
      using two tests recognised for the assessment of anxious behaviour: the light
      dark discrimination test and the staircase test.

PMID- 10922530
TI  - Measuring temperament in rhesus macaques: consistency and change in emotionality
      over time.
AB  - This study of rhesus macaques (Macaca mulatta) investigated whether individual
      differences in emotionality, as measured by scratching frequencies, are stable
      over time and across seasons. Five adult females living in captive social groups
      were observed during two consecutive birth seasons and five females during the
      birth and the mating season. Scratching frequencies were higher during the birth
      than during the mating season, suggesting that the presence of infants was
      associated with elevated emotionality. Individual differences in scratching
      frequencies remained stable across two consecutive birth seasons, but there was
      no significant correlation between scratching frequencies in the birth and in the
      mating season. These findings suggest that, under certain circumstances,
      individual differences in emotionality are consistent over time and that
      scratching may be used as a non-invasive indicator of temperament.

PMID- 10922950
TI  - [Abdominal actinomycosis. Report of three cases and review of the literature].
AB  - Actinomyces are Gram positive, anaerobic, filamentous bacteria, saprophytes of
      the oral cavity and intestinal tract of humans. They rarely cause chronic
      suppurative infections. Abdominal abscess can masquerade as a malignant process
      and lead to a surgical intervention with resection. We report three patients with
      abdominal actinomycosis; the first affected the liver with a favorable outcome on
      medical treatment, the second of abdomino-pelvic localisation was related to an
      intra-uterine device and the last affecting the transverse colon simulated a
      malignant process and required an hemicolectomy. These observations illustrates
      the difficulties of the diagnosis of this rare and unrecognized disease.

PMID- 10922951
TI  - [Drug-induced oral ulcerations].
AB  - Different side effects of drugs have been described in the oral cavity, including
      oral ulcerations. Direct contact between drugs and oral mucosa may induce
      chemical burn or local hypersensitivity. Less frequently, these drug-induced oral
      ulcerations are part of a complex reaction with cutaneous or systemic
      manifestations. Sometimes, one or more oral ulcerations appear as the main side
      effect of a drug, or exceptionally as solitary lesions. Solitary oral ulcerations
      usually appear after few weeks of treatment. In most of cases, these lesions
      resist to conventional treatments, with a rapid healing following the suppression
      of the responsible drug. This diagnosis is usually difficult, particularly with
      patients receiving multiple drug therapy. Besides, special attention must be paid
      to new drugs. Oral ulcerations following symptoms of burning mouth, metallic
      taste, dysgueusia or agueusia are strongly suggestive of a pharmacological
      origin. Most of the molecules able to induce solitary oral ulcerations are
      commonly prescribed in a) rheumatology: NSAI (diclofenac, flurbiprofen,
      indomethacin, naproxen), long-term rheumatoid arthritis therapy (azathioprine,
      methotrexate, penicillamine, gold compounds, tiopronin); b) cardiology:
      angiotensin-converting-enzyme inhibitors (captopril, enalapril), angiotensin 2
      receptor antagonist (losartan), anti-angorous (nicorandil), c) psychiatry:
      antidepressants (fluoxetine, lithium), d) AIDS therapy (foscarnet, zalcitabine).

PMID- 10922952
TI  - [Current situation of nucleoside reverse transcriptase inhibitors].
AB  - Nucleosidic reverse transcriptase inhibitors were the first class of drugs to be
      used for the treatment of HIV disease. Recent data on the complex pathways
      allowing the virus to adapt to the drugs will lead to better management of the
      phenomena. Similarly, better understanding of the mechanism of their toxicity
      will allow safer use. As these drugs are simple to use, and have a sustained
      effect over time with reasonable tolerance, nucleosidic reverse transcriptase
      inhibitors are currently the main contributors to multi-drug anti-HIV regimens.
      Reverse transcriptase inhibitors are currently the main contributors in multi
      drug anti-HIV regimens.

PMID- 10922953
TI  - [Non-nucleoside reverse transcriptase inhibitors].
AB  - The non-nucleoside reverse transcriptase inhibitors (NNRTIs) directly inhibit the
      HIV-1 reverse transcriptase (RT) by binding in a reversible and non-competitive
      manner to the enzyme. The currently available NNRTIs are nevirapine, delavirdine,
      and efavirenz; other compounds are under evaluation. NNRTIs are extensively
      metabolized in the liver through cytochrome P450, leading to pharmacokinetic
      interactions with compounds utilizing the same metabolic pathway, particularly
      PIs, whose plasma levels are altered in the presence of NNRTIs. NNRTIs are drugs
      with a low genetic barrier, i.e. a single mutation in RT genoma induces a high
      level of phenotypic resistance, preventing the use of NNRTIs as monotherapy. In
      naive patients, several trials have shown the value of NNRTIs in combination with
      nucleosides and/or protease inhibitors. Small pilot studies have shown that
      NNRTIs may be useful as second-line therapy. However, due to the rapid emergence
      of resistant virus to these compounds in case of incomplete viral suppression,
      NNRTIs should not be added to current failing antiretroviral regimen. The most
      common side-effect reported with nevirapine and delavirdine is rash. The
      incidence of rash is rather similar under these two compounds, but severe rash is
      less frequent with delavirdine. The most common adverse reactions reported with
      efavirenz are central nervous system complaints such as dizziness. Rash is
      reported less frequently than with nevirapine or delavirdine, and is usually
      mild. NNRTIs resistance mutations are located in the amino acid residues aligning
      the NNRTI-binding "pocket" site. High-level resistance is often associated with a
      single point mutation which develops within this site (especially codon groups
      100 - 108 and 181 - 190). Patients failing on one NNRTI are very likely to
      possess multiple NNRTI resistance mutations. NNRTIs should always be used as part
      of a potent antiretroviral therapy to insure suppression of viral replication,
      thus circumventing the rapid selection of cross-resistant variants.

PMID- 10922954
TI  - [HIV protease inhibitors].

PMID- 10922955
TI  - [Metabolic complications associated with use of protease inhibitors].
AB  - The potency of highly active antiretroviral therapy, including protease
      inhibitors have led to declining morbidity and mortality in patients with HIV
      infection. However the use of protease inhibitors is associated with onset of
      morphologic and metabolic disorders. A syndrome of lipodystrophy has been
      described. It is characterized by fast wasting of the face and limbs, and a
      central adiposity, breast hypertrophy and buffalo neck. The prevalence of
      lipodystrophy in patients treated with protease inhibition is about 60%. The
      principal metabolic disorders are lipid abnormalities, principally
      hypertriglyceridemia. New onset of diabetes mellitus is less frequent. The
      pathogenesis of these abnormalities unknown. Insulin resistance seems to be a
      common feature of protease inhibitor associated metabolic an morphologic side
      effects.

PMID- 10922957
TI  - [The value of plasma antiretroviral drug monitoring in the management of HIV
      infected patients].
AB  - Antiretroviral drugs exhibit significant between-patient pharmacokinetic
      variability. Over the past years, data have emerged demonstrating a link between
      antiretroviral drug concentrations and efficacy or side-effects. As a result, the
      issue of therapeutic drug monitoring for these compounds are arisen; many
      published studies provided evidence that plasma concentrations contributes to
      therapeutic response. However, further information must be collected to define
      more precisely the therapeutic concentrations and the indications of therapeutic
      drug-monitoring for each drug.

PMID- 10922956
TI  - [Anti-HIV chemoprophylaxis for blood-exposure accidents].
AB  - Chemoprophylaxis against HIV after accidental blood exposures represents a new
      indication for antiretroviral drugs. Efficacy has been suggested by the results
      of a case-control study in health care workers and the reduction of mother to
      infant transmission of HIV with zidovudine. The post-exposure treatment should be
      given as soon as possible, and in the latest at 48 hours. National guidelines
      recommend a triple therapy with or without protease inhibitor, adapted to the
      source patient. The evaluation of efficacy needs a standardized follow-up.

PMID- 10922958
TI  - [Adherence to antiretroviral treatments with a protease inhibitor in HIV-infected
      patients].
AB  - OBJECTIVE: Long-term therapeutic success of powerful antiretroviral treatments
      dependent on patient adherence. This study was conducted to assess the
      difficulties HIV-infected patients with advanced-stage disease encounter in
      adhering to antiretroviral treatments with a protease inhibitor. PATIENTS AND
      METHODS: A prospective self-administered questionnaire survey was conducted at
      our outpatient clinic for 2 months. CD4 counts and HIV viral loads were also
      determined. RESULTS: Seventy-one percent of the study population which included
      262 responded to the questionnaire. The survey was made a median 215 days after
      initiating the antiprotease treatment with indinavir (71% of the cases),
      ritonavir (13%), saquinavir (6%), or a combination of protease inhibitors (10%).
      At onset of antiprotease treatment, mean CD4 count was 171+/-150/mm(3) and mean
      HIV viral load was 75,000 copies/ml. The treatment was considered to be difficult
      to take by 43% of the patients; 66% stated they had forgotten to take their drugs
      at least once a month. It was most difficult to take the drugs prescribed for the
      afternoon. Shifts of 1 hour were observed in 58% of patients. Non-adherence was
      frequent (1 failure to take drugs per week), observed in 13% of patients. Most
      often, the patients stated they had forgotten to take their drugs because of
      occupational or relational difficulties (52%). Non-adherence increased with
      duration of treatment. The drug most often associated with non-adherence was
      indinavir (73%). Age and sex did not influence adherence. Mean RNA HIV serum
      level was lower than at onset of the antiprotease treatment in the most non
      adherent patients. At the time of the questionnaire, there was no difference in
      serum RNA HIV level or in the percentage of patients with an undetectable level
      between non-adherent and adherent patients. CONCLUSION: This survey confirmed
      difficulties in adherence are frequent and worsen with time. No relationship was
      found between non-adherence and reduction in viral load, suggesting that a short
      term effect of these very active drugs despite lack of perfect adherence. Other
      factors (pharmacology, sensitivity to antiretroviral drugs.) also play a major
      role in therapeutic success.

PMID- 10922959
TI  - Brachial plexopathy associated with diffuse edematous scleroderma.
AB  - Peripheral nervous system (PNS) involvement is rare in systemic sclerosis (SSc),
      usually restricted to peripheral nerve entrapment. To our knowledge, only one
      case of scleroderma with brachial plexus involvement has been reported
      previously. We report here on a 61-year-old woman with past history of limited
      cutaneous SSc who developed motor deficiency in the left arm concomitant with
      diffuse edematous scleroderma without evidence for trauma or compression of the
      brachial plexus. After six months intravenous pulse cyclophosphamide therapy,
      dramatic improvement of skin and neurological involvement was observed.

PMID- 10922960
TI  - Favorable outcome of gemcitabine-induced respiratory distress syndrome.
AB  - Gemcitabine, a deoxycytidine analog, is used to treat solid tumors, like non
      small-cell lung carcinoma. The most commonly reported adverse effects are
      reversible and generally not fatal. However, among the five cases of acute
      respiratory distress syndrome (ARDS) secondary to gemcitabine treatment reported
      since 1997, four were fatal despite corticosteroid therapy. We describe here a
      patient who received gemcitabine for bronchial epidermoid carcinoma and developed
      ARDS which spontaneously regressed after gemcitabine withdrawal.

PMID- 10922961
TI  - [Guillain-Barre syndrome and Mycoplasma pneumoniae infection].
AB  - Guillain-Barre syndrome subsequent to Mycoplasma pneumoniae is uncommon and
      difficult to confirm. We report one case. Clinical presentation and therapy were
      unremarkable. The interest of antibiotics (preventive or curative) is unresolved.
      The pathophysiology remains hypothetical but Mycoplasma pneumoniae and some
      surface gangliosides of peripheral nerves share homologous epitopes leading to
      the production of antibodies. Induced antibodies to ganglioside may cross-react
      with neural tissues.

PMID- 10922962
TI  - [Malignant paraganglioma of the uterus].
AB  - We report a malignant uterine paraganglioma in a 41-year-old woman who underwent
      a hysterectomy for meno-metrorrhagia. It was initially thought to be a leiomyoma
      in necrobiosis. The clinical outcome was characterized by an early regional
      recurrence (in the left Fallopian tube). Later, vertebral and lung metastasis
      occurred, leading to death 22 months after the initial diagnosis. Paragangliomas
      are uncommon neuroendocrine tumors, related to pheochromocytomas. They are mainly
      found in the para-aortic and retroperitoneal region, and less commonly in the
      pelvic area. Location in the uterus is extremely rare: 5 cases were previously
      reported and only one malignant.

PMID- 10922963
TI  - [Pyoderma gangrenosum and breast cancer: a new case].
AB  - We report here a new case of pyoderma gangrenosum (PG) associated with a breast
      cancer in a 39-year-old woman. We only found in literature three other reports of
      this rare entity which seems usually to be associated with monoclonal gammopathy,
      gastro-intestinal diseases such as Crohn's disease, chronic ulcerative colitis,
      leukemias or rheumatologic diseases. A commun hapten between of tumor and skin
      may explain the origin of this inflammatory lesion. In our case, PG could be a
      paraneoplastic syndrome.

PMID- 10922964
TI  - [Kikuchi-Fujimoto's disease and systemic lupus erythematosus].

PMID- 10922966
TI  - Diabetic nephropathy: a nephrological point of view.

PMID- 10922965
TI  - [Ehlers-Danlos syndrome disclosed by an intramural hematoma of the duodenum].

PMID- 10922967
TI  - Diabetic nephropathy: what are the diabetologist's expectations?

PMID- 10922968
TI  - Structural involvement in type 1 and type 2 diabetic nephropathy.
AB  - Structural changes underlying diabetic nephropathy in Type 1 diabetes are
      prodominant in the glomerulus [thickening of glomerular basement membrane (GBM)
      and mesangial expansion], but also include arteriolar, tubular and interstitial
      lesions. The structural measure that correlates best with all renal functional
      parameters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an
      estimate of mesangial expansion. Structural-functional relationships in Type 2
      diabetes are much less known. These studies investigated renal structure in the
      early stages of nephropathy [microalbuminuria (MA)] in patients with Type 1 and
      Type 2 diabetes. Diabetic glomerulopathy was quite advanced in Type 1 diabetic
      patients with MA, and both Vv (mes/glom) and GBM width were increased as compared
      to normoalbuminuric (NA) patients when the albumin excretion rate (AER) was > 30
      microgram/min. Serial renal biopsies were performed 5 years apart in 11 Type 1
      diabetic patients to evaluate whether glomerular and interstitial lesions
      progress jointly. AER increased significantly in 5 years, while the glomerular
      filtration rate remained unchanged. All structural parameters were initially
      abnormal. Vv(mes/glom) and mean glomerular volume increased significantly,
      whereas GBM width and the interstitial volume fraction were unchanged. Moreover,
      the change in Vv (mes/glom) was correlated with the change in AER (r =0.64, p
      <0.05). Thus, at the disease stage during which some patients progress to MA or
      proteinuria, continuing mesangial expansion is the main variable, whereas further
      interstitial expansion does not occur. A large number of Type 2 patients were
      also studied. Early diabetic glomerulopathy was detected by electron microscopy
      in NA patients and found to be more advanced in those with MA and proteinuria.
      However, lesions were milder than in Type 1 diabetic patients, and there was
      considerable overlap between groups. Morphometric results by electron microscopy
      were similar to those by light microscopy, demonstrating the heterogeneity of
      renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had
      typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial
      and/or vascular lesions and 30% had normal renal structure.

PMID- 10922969
TI  - Growth factors, cytokines, and renal fibrosis during the course of diabetic
      nephropathy.
AB  - Diabetic nephropathy is characterised by a progressive accumulation of
      extracellular matrix within the glomerular mesangium and the interstitium. The
      pathogenesis of this fibrotic process is still poorly understood, but in vitro
      and in vivo data suggest that TGF-B plays a key role. Local overproduction of TGF
      B could be secondary to a synthesis of diacylglycerol, polyols, or glucosamines.
      It may also be secondary to an accumulation of advanced glycosylation end
      products which modify the functions of neighbouring cells. Moreover, clinical as
      well as experimental data for TGF-B suggest that angiotensin II has a profibrotic
      effect; and it has been clearly demonstrated that angiotensin-converting enzyme
      inhibitors have a beneficial effect in patients with insulin-dependent diabetes
      mellitus. Other molecules such as endothelin-1, lipid peroxidation products, or
      IGF-1 may also play a role in this fibrotic process. Finally, heavy proteinuria
      secondary to glomerular lesions enhances the accumulation of extracellular matrix
      within the interstitium, probably through modifications of tubular cell
      functions, thereby inducing the release of pro-inflammatory and profibrotic
      molecules.

PMID- 10922970
TI  - Role of metalloproteases and inhibitors in the occurrence and progression of
      diabetic renal lesions.
AB  - Renal remodelling in hyperinsulinic/insulinopenic states is mediated by
      glucotoxicity, endothelial dysfunction and vascular and nephron collagen
      turnover. Hypertensive and renal links are renewed by renoprotective
      interventions of renin-angiotensin. Vasoactive peptide processing and vascular
      collagen deposition are under the tight control of two zinc metalloproteinase
      families that regulate vascular tone and trophicity: gluzincins (or
      vasopeptidases) are convertases of angiotensins, endothelins or atrial
      natriuretic factors; and metzincins or matrix metalloproteases (MMP, matrixins)]
      regulate vascular type IV collagen basement membrane proteolysis. Association of
      natural tissue inhibitors of MMPs, pharmacological inhibitors of vasopeptidases
      [either conventional (angiotensin-converting enzyme inhibitors) or innovative
      (omapatrilat)], together with synthetic MMP inhibitors, are currently screened to
      counteract vascular remodelling and renal scarring. Our studies focused on the 72
      kDa (MMP-2) and 92 kDa (MMP-9) matrixin gelatinases and tissue inhibitors
      involved in basement membrane degradation and rebuilding. Three complementary
      settings were developed, allowing evaluations from basic to clinical stages. A
      leucocyte-endothelial transmigration model was designed for transcription and
      addressing of enzymes and inhibitors, in situ matrix degradation, and blockading
      by metalloprotease inhibitors (captopril). Insulin-resistant fructose-fed rats
      showed heavy proteinuria and glomerulosclerosis involving angiotensin II
      dependent changes in renal gelatinases and inhibitors. Urinary gelatinolytic
      profiles from Type 2 diabetic patients with overt nephropathy were compared with
      those of normal first-degree relatives and age-matched healthy controls.
      Physiologically, MMP-9 was the primary urinary gelatinolytic enzyme. In Type 2
      diabetic proteinuric patients, MMP-9 and MMP-2 releases were significantly
      increased in the absence of renin-angiotensin blockade, while first-degree
      relatives showed reduced gelatinase levels suggestive of a genetic control of
      renal matrix regulation prior to potential glycaemic dysregulation. These
      preliminary data suggest that local MMP/TIMP imbalance is involved in diabetic
      renal remodelling. Further studies are needed to define the redundancies and
      specificities of vasopeptidase and MMP inhibitors, differentiate the
      antihypertensive effect from target-organ protection, screen for innovative
      pharmacological compounds, and validate simple, efficient biological markers of
      renal fibrosis progression and the effect of anti-fibrotic therapeutic
      interventions.

PMID- 10922971
TI  - Hereditary factors in the development of diabetic renal disease.
AB  - The role of genetics in diabetic renal disease has been suspected on the basis of
      follow-up and familial studies. Barely half of Type 1 patients who develop a
      diabetic retinopathy also develop nephropathy, and the relative risk of
      nephropathy for a diabetic proband is around 3 if a sib is affected. Candidate
      genes for diabetic nephropathy can be divided into two categories: those
      affecting glucose metabolism in target organs of diabetic microangiopathy, and
      those affecting renal changes in response to hyperglycaemia. The role of
      angiotensin-I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has
      been suspected for several years. Evidence of its possible role in the
      development and progression of diabetic renal disease is presented here.

PMID- 10922972
TI  - Blood pressure, diabetes and diabetic nephropathy.
AB  - Despite multiple evidence-based data that diabetic nephropathy is largely
      preventable and its progression slowed by currently available interventions
      diabetic patients are often undertreated, especially for the lowering of blood
      pressure. Recent studies, (HOT Syst-Eur, SHEP, UKPDS, CAPPP, ABCD, HOPE) have
      confirmed the efficiency of intensively treated blood pressure in reducing
      morbidity-mortality in this group of patients at high risk. Low blood pressure
      targets are mandatory, but may not be that easy to achieve, especially in the
      presence of renal failure. Early prescription of a combination of
      antihypertensive drugs is often neccessary. Thus, the clinical question relates
      to the best combination of drugs. Most studies in hypertensive diabetic patients
      have dealt with 3 classes of antihypertensives drugs: diuretics, beta-blockers
      and ACE-inhibitors. Diuretics are one of the most efficient hypotensive drugs
      available for treatment of hypertension in diabetic patients. Their use must be
      encouraged early in the stepped approach since diabetes is usually associated
      with mid-volume expansion due to hyperinsulinism and hyperadrenergic state. In
      spite of the proven benefit of beta-blockers in diabetic patients, these drugs
      are largely underused. The indications for selective beta-blockers should
      probably be broadened for most diabetic patients in primary prevention. Beta
      blockers are essential in secondary prevention for patients with coronary artery
      disease and hypertension. ACE-inhibitors are now more and more widely prescribed
      in diabetic patients at all stages of hypertension and nephropathy, but
      paradoxally their use has not been validated in Type 2 diabetic nephropathy. When
      the desired blood pressure target is obtained, cardiovascular outcome and
      probably also progression of diabetic nephropathy are significantly improved
      independently of a specific drug. Early combination therapy, including ACE
      inhibitors, diuretics and beta-blockers, should be promptly proposed to all
      hypertensive diabetic patients to achieve low blood pressure and prevent high
      cardiovascular burden and progression of nephropathy.

PMID- 10922973
TI  - Lipids, protein intake, and diabetic nephropathy.
AB  - Progressive impairment of kidney function is one of the major problems in
      diabetic patients. Control of glycaemia and blood pressure is the main strategy
      for preventing or slowing impairment in renal function in this condition.
      However, contributing factors such as hyperlipidaemia and high protein intake
      have now been identified, and their control can be regarded as a complementary
      measure. The role of lipid abnormalities and hypercholesterolaemia in the
      pathogenesis of glomerular injury has been demonstrated in animal models, and a
      link between hypercholesterolaemia and diabetic nephropathy has been established
      in humans. To date, few intervention studies in diabetic patients have shown a
      slower decline in renal function. Nonetheless, in every study in which follow-up
      was long enough, cholesterol lowering had a beneficial effect on renal function.
      Although hypercholesterolaemia may not be the cause of renal injury, it
      represents an aggravating factor. High serum cholesterol seems to have a similar
      action on glomerular mesangial cells and endothelial cells. This appears to be
      analogous to the process of atherosclerosis, as mesangial cells possess binding
      sites for LDL and oxidised LDL, help recruit macrophages and secrete
      proliferative factors. Protein intake is another factor that can influence renal
      deterioration. Two meta-analyses have confirmed the beneficial effect of a low
      protein diet in diabetic nephropathy, showing no adverse effects on the glycaemic
      control. Protein intake even seems to enhance the sensitivity of tissues and
      liver to insulin. Thus, there appear to be no contraindications to such diets in
      well-controlled diabetic patients. In short, although glycaemic and blood
      pressure control are still the main lines of treatment for diabetic patients,
      lowering blood cholesterol and restricting protein intake represent complementary
      measures that can help slow renal impairment.

PMID- 10922974
TI  - Smoking: a factor promoting onset and progression of diabetic nephropathy.
AB  - Although smoking was identified two decades ago as a factor promoting the onset
      and progression of nephropathy in Type 1 and then in Type 2 diabetes, its role
      has been largely neglected. More recently, it has been shown that smoking
      adversely affects renal haemodynamics and protein excretion even in subjects
      without renal disease. In addition, it impairs the prognosis for renal function
      in patients with non-diabetic renal disease. Recent studies have suggested the
      involvement of sympathetic activation, increased endothelin production, and
      impaired endothelial cell-dependent vasodilatation in the genesis of smoking
      induced renal function impairement. Cessation of smoking apparently slows
      progression to renal failure, but the decision to stop smoking is difficult
      because of the high addictive potential of the habit. The challenge remains for
      diabetologists and nephrologists to motivate patients to stop smoking.

PMID- 10922975
TI  - Microalbuminuria, endothelial dysfunction and cardiovascular risk.
AB  - Microalbuminuria was originally considered to be an important new risk factor for
      diabetic nephropathy. More recently, it has been convincingly shown that
      microalbuminuria is also an independent risk factor for cardiovascular morbidity
      and mortality in Type 1 and Type 2 diabetic patients. Even in the non-diabetic
      background population, microalbuminuria is a risk factor for cardiovascular
      mortality. What is the link between increased loss of albumin in urine and
      cardiovascular disease and mortality? As microalbuminuria is apparently
      associated with increased universal vascular sieving of albumin in terms of the
      transcapillary escape rate of albumin (TER-alb), microalbuminuria may reflect
      this universal sieving. The pathophysiology of increased TER-alb is unknown, but
      could be caused by haemodynamics or damage to the functional properties of the
      vascular wall. A number of studies have provided evidence of endothelial
      dysfunction in patients with microalbuminuria, which may be the common link
      accounting for the associations mentioned above. In this context, a number of
      markers of endothelial cell dysfunction have been found to be increased in
      patients with microalbuminuria. In addition, a number of functional in vivo tests
      of endothelial dysfunction have been performed in Type 1 and Type 2 diabetic
      patients as well as in normal controls. Overall, these studies indicate the
      existence of a functional vascular dysfunction in Type 1 diabetic patients and
      normal controls with microalbuminuria, which may be related to dysfunction of
      endothelial cells.

PMID- 10922976
TI  - The diabetic patient with renal insufficiency.
AB  - Diabetic mellitus is often complicated by nephropathy with progression to renal
      failure. Most patients with clinical diabetes who present with renal
      insufficiency have diabetic glomerulosclerosis, although some (particularly in
      Type 2 diabetes) present with other glomerular diseases. The purpose of this
      study was to provide practical recommendations for the management of patients
      with diabetes and renal failure and evaluate the prevalence of non-diabetic
      glomerulopathies in Type 2 diabetic patients. Various forms of glomerulonephritis
      have been associated with diabetes, occasionally leading to alternative
      management of these patients in attempts to reverse or contain renal failure.

PMID- 10922977
TI  - Management of drugs affecting blood glucose in diabetic patients with renal
      failure.
AB  - Prevention of the onset or worsening of microalbuminuria by good blood glucose
      control has been confirmed in Type 2 diabetes, though not at the stage of chronic
      renal failure (CRF). Thus, it would seem desirable to maintain strict blood
      glucose control whenever circumstances allow. If prescribed sulphonylureas (SU)
      are effective, they can be continued at adjusted doses until an advanced stage of
      CRF, subject to strict monitoring. SU are eliminated by the liver, but their
      metabolites (often active) are eliminated to varying degrees by the kidney. Non
      SU insulin secretagogues and thiazolidinediones metabolised by the liver might
      also be used. The fate of their metabolites (some active) remains to be defined
      in CRF, and further clinical trials are required. Acarbose and its metabolites,
      as well as miglitol, very probably accumulate in CRF, causing ill-defined (but
      especially hepatic) iatrogenic risks. Although the danger of metformin in
      diabetic patients with renal failure is currently uncertain, CRF remains a
      regulatory contraindication. Insulin, which is necessary in most Type 2 diabetic
      patients with CRF, decreases as CRF progresses and when dialysis is started. The
      kinetics of insulin analogs are modified in CRF. Regardless of the choice of
      treatment, specialist and regular monitoring is required.

PMID- 10922978
TI  - Kidney and kidney-pancreas transplantation in diabetic recipients.
AB  - Type 1 as well as Type 2 diabetic patients in end-stage renal failure and with no
      contraindications to kidney transplantation have a greater probability of
      survival with a functioning kidney graft than if they remain on dialysis. Five
      year patient and pancreas graft survival rates for simultaneous kidney-pancreas
      transplantation are currently 81 and 67% respectively. The main benefit of this
      operation is to achieve insulin independence and improved quality of life.
      However, surgical morbidity is higher and the immunosuppressive regimen more
      powerful than for kidney transplantation alone. The 5-year survival rate for
      kidney transplantation in Type 2 patients without severe cardiovascular disease
      is 81%, although a high incidence of peripheral vascular complications can be
      expected. Renal transplantation should be considered in diabetic patients with a
      life expectancy of more than 5 years, no contraindications to immunosuppressive
      treatment, and low perioperative risk. Combined kidney-pancreas transplantation
      should be considered in Type 1 patients under 50 years of age with no or moderate
      cardiovascular complications and a thorough understanding of the risks and
      benefits of the procedure.

PMID- 10922979
TI  - Prevalence of renal artery stenosis in type 2 diabetes.
AB  - Renal artery stenosis (RAS) was searched for in a Type 2 diabetes population (n
      =208) with severe hypertension (SHT) and/or renal deficiency (RD) and/or severe
      macroangiopathy (MA), using arteriography and/or duplex colour scan (with
      confirmation by arteriography or magnetic resonance angiography). Thirty-four
      (16.3 %) cases had significant RAS >=70% (83% unilateral, 17% bilateral; 11.7%
      with total thrombosis). High significance (P<0.01) (34 RAS vs 174 subjects
      without RAS) was found for male predominance (sex ratio 0.8), smoking (47%),
      insulin requirement (65%), prevalence and severity of decreased renal function
      (65%), severe hypertension (53%), and prevalence of macroangiopathy (82%),
      especially in association with coronary heart disease (65%). RAS prevalence was
      low in subjects with only 1 (8%) diagnostic criterion and high when 2 (21%) or 3
      (41%) signs were present, regardless of the criterion (HT/RD/MA). A high increase
      of RAS prevalence was found in males, smokers and patients with heart disease or
      macroalbuminuria when 2 or 3 diagnostic criteria were present (no increased
      prevalence for only 1 criterion). RAS screening should be performed in a Type 2
      diabetic population with HT, RD, or MA by opacification of the renal arteries at
      the same time as arteriography for control of another vessel, or by duplex colour
      scan when 2 or 3 diagnostic criteria are present. This attitude allows a
      diagnostic score of 85 % of RAS in this Type 2 diabetic population.

PMID- 10922980
TI  - Imaging and endovascular treatment of renal artery stenosis in the diabetic
      patient.
AB  - Although diabetes is a classical risk factor for macroangiopathy, the prevalence
      of renal artery stenosis (RAS) in this type of pathology has not been clearly
      determined. More than 50% of RAS occur in diabetic patients (almost exclusively
      Type 2), whereas autopsy findings and the few clinical surveys reported indicate
      that the percentage of RAS within the diabetic population is close to 30%. RAS
      occur especially in elderly subjects with Type 2 diabetes and multiple vascular
      involvement, and bilateral stenoses are frequent. Diagnostic imaging of RAS can
      cause adverse effects in the diabetic patient if iodinated contrast media are
      used, especially in cases of renal insufficiency. The presence of this risk
      factor requires that iodinated radiological explorations be performed with due
      caution, or that another product be substituted as a contrast agent (CO(2) or
      gadolinium), or that an imaging technique without iodine be used (colour Doppler
      ultrasound, magnetic resonance angiography). The therapeutic management of RAS in
      the diabetic patient differs little from that employed for other atheromatous
      stenoses of the renal artery. Endovascular treatment of RAS is the technique of
      choice for most patients, whether diabetic or not. The existence of diabetes has
      little effect on therapeutic strategy, except in cases of renal insufficiency
      when the risk of iodine overload should limit the doses of contrast medium or
      require the partial or even total substitution of another agent (CO(2),
      gadolinium). As in the case of other RAS, the indications depend on the lesion
      and the clinical presentation. Similarly, the results are both clinical and
      anatomical, and the existence of diabetes has a limited impact on these different
      parameters.

PMID- 10922981
TI  - Presidential address: evolution.

PMID- 10922982
TI  - IL-4-induced activation of the Stat6 pathway contributes to the suppression of
      cell-mediated immunity and death in sepsis.
AB  - BACKGROUND: Although studies have shown that there is a marked depression in cell
      mediated (T(H)(1)) immunity after the onset of sepsis, the mechanism by which
      this occurs remains unknown. In this regard, the T(H2) cytokine IL-4 is known to
      regulate T(H1) and T(H2) cell responsiveness primarily through the activation of
      the signal transducer and activation of transcription factor-6 (Stat6) pathway.
      METHODS: We hypothesized that IL-4 may contribute to the suppression of cell
      mediated immunity and to death seen in sepsis and that IL-4 may be acting through
      the Stat6 pathway. To determine this, we induced cecal ligation and puncture
      (CLP) or sham-CLP in male BALB/c mice. Mice received 2 mg of monoclonal antibody
      against IL-4 or IgG control at 12 hours after CLP (ie, at the onset of immune
      suppression). Splenic T cells were then isolated 24 hours after CLP and
      stimulated with monoclonal antibody to CD3. Cytokine release and Stat6
      phosphorylation (activation) were determined. In a separate group of animals,
      survival was assessed over 10 days. RESULTS: The results indicate that after CLP,
      T cells are suppressed in their ability to release the T(H1) cytokines, IL-2 and
      IFN-gamma. Alternatively, the release of T(H2) cytokines IL-10 and IL-4 is
      markedly increased after CLP. This was associated with an increase in
      phosphorylated Stat6 protein. In vivo treatment of mice with monoclonal antibody
      to IL-4 at 12 hours after CLP restores T(H1) responsiveness while preventing the
      increase in T(H2) cytokine release and Stat6 phosphorylation. Furthermore,
      neutralization of IL-4 markedly increased the survival rates in septic animals.
      CONCLUSIONS: Taken together, these data indicate that the T(H2) cytokine IL-4
      contributes to the suppression of cell-mediated immunity and death associated
      with polymicrobial sepsis and suggest that IL-4 may be acting through the Stat6
      pathway in septic animals.

PMID- 10922983
TI  - Practical guidelines for optimal gamma probe detection of sentinel lymph nodes in
      breast cancer: results of a multi-institutional study. For the University of
      Louisville Breast Cancer Study Group.
AB  - INTRODUCTION: Multiple radioactive lymph nodes are often removed during the
      course of sentinel lymph node (SLN) biopsy for breast cancer when both blue dye
      and radioactive colloid injection are used. Some of the less radioactive lymph
      nodes are second echelon nodes, not true SLNs. The purpose of this analysis was
      to determine whether harvesting these less radioactive nodes, in addition to the
      "hottest" SLNs, reduces the false-negative rate. METHODS: Patients were enrolled
      in this multicenter (121 surgeons) prospective, institutional review board
      approved study after informed consent was obtained. Patients with clinical stage
      T1-2, N0, M0 invasive breast cancer were eligible. This analysis includes all
      patients who underwent axillary SLN biopsy with the use of an injection of both
      isosulfan blue dye and radioactive colloid. The protocol specified that all blue
      nodes and all nodes with 10% or more of the ex vivo count of the hottest node
      should be removed and designated SLNs. All patients underwent completion level
      I/II axillary dissection. RESULTS: SLNs were identified in 672 of 758 patients
      (89%). Of the patients with SLNs identified, 403 patients (60%) had more than 1
      SLN removed (mean, 1.96 SLN/patient) and 207 patients (31%) had nodal metastases.
      The use of filtered or unfiltered technetium sulfur colloid had no impact on the
      number of SLNs identified. Overall, 33% of histologically positive SLNs had no
      evidence of blue dye staining. Of those patients with multiple SLNs removed,
      histologically positive SLNs were found in 130 patients. In 15 of these 130
      patients (11.5%), the hottest SLN was negative when a less radioactive node was
      positive for tumor. If only the hottest node had been removed, the false-negative
      rate would have been 13.0% versus 5.8% when all nodes with 10% or more of the ex
      vivo count of the hottest node were removed (P =.01). CONCLUSIONS: These data
      support the policy that all blue nodes and all nodes with 10% or more of the ex
      vivo count of the hottest SLN should be harvested for optimal nodal staging.

PMID- 10922984
TI  - Interpretation of computed tomography does not correlate with laboratory or
      pathologic findings in surgically confirmed acute appendicitis.
AB  - BACKGROUND: Computed tomography (CT) is used increasingly to diagnose acute
      appendicitis, despite variable technique and interpretation. We hypothesized that
      CT interpretation would not reflect actual clinical-pathologic findings in all
      demographic patient groups. METHODS: A prospective university hospital database
      of 625 consecutive patients (1995-1999), all of whom were operated on for
      appendicitis (261, or 41.8%, within 24 hours of discretionary CT), was reviewed.
      CT and pathology data were obtained from final, written reports. CT criteria
      included free fluid or air, appendiceal visualization, mesenteric fat stranding,
      and blurred pericecal fat. Appendix pathology included acute, gangrenous, and
      perforated organs. Statistics were performed with the Fisher exact test
      (coordinate data) and univariate analysis of variance (continuous data);
      multivariate analysis of variance for independent effects on dependent variable
      (positive CT or pathology; P <.05). RESULTS: The mean age was 35 +/- 1 years with
      46.6% being female patients. CT was done more often in women and after 1997 (both
      P <.05). The sensitivity and specificity of CT were 96.1% and 16.1%,
      respectively. The positive predictive value (PPV) and accuracy rate (A) were 90%,
      and 88%, respectively. After CT, the incidence of finding a normal appendix was
      lower (19.3% vs 12.3%, P <.05), especially if the white blood cell count (WBC)
      was normal (< or = 11K/microL, 6.1% vs 23.2%, P <.001). If the WBC was < or =
      11K/microL with positive CT, PPV/A was 73. 7%/71.3%, whereas with WBC >
      11K/microL and positive CT, PPV/A was 99.4%/93.3%. Multivariate analysis of
      variance showed that none of the individual variables used by the radiologist to
      determine a positive CT scan correlated with outcome determined by surgical
      pathology. A healthy appendix was predicted by a CT interpreted as negative and
      younger age (both P <.05), and especially by lower WBC (P <.0001), but not by
      gender or surgeon. CONCLUSIONS: Although the negative appendectomy rate was
      decreased by CT, there was no correlation between CT findings and pathologically
      proved disease. Other factors such as more precise patient selection by clinical
      criteria may also be improving outcome. A positive CT scan in a patient with a
      normal WBC should be interpreted with caution.

PMID- 10922985
TI  - HER2 regulatory control of angiopoietin-2 in breast cancer.
AB  - BACKGROUND: HER2 overexpression is a marker of aggressive breast cancer. Tumors
      that overexpress HER2 induce endothelial cell retraction and endothelial
      destabilization. Because angiopoietin-2 (Ang-2) also destabilizes microvessels,
      we postulated that HER2 signaling upregulates Ang-2 as a mechanism of
      angioinvasion. METHODS: We tested human breast cancers and breast cancer cell
      lines for coexpression of HER2 and Ang-2 with Northern blot, reverse
      transcriptase-polymerase chain reaction, and enzyme-linked immunosorbent assay.
      Further, we manipulated HER2 signaling with 100 ng/mL MAbHu HER2 (Herceptin;
      Genentech, San Francisco, Calif) and Heregulin beta1 (100 ng/mL; R&D Systems,
      Inc, Minneapolis, Minn) to test for HER2 regulation of Ang-2 production. RESULTS:
      Three of 4 breast cancer cell lines expressed HER2 protein and Ang-2 mRNA. HER
      cells, a stably transfected cell line that overexpresses HER2 6-fold, showed a
      430% increase in Ang-2 mRNA compared to parental MCF-7 cells. Heregulin beta1
      stimulation of HER2 signaling in MCF-7 cells increased Ang-2 by 20% (P <.05).
      HER2 signaling blockade with 100 ng/mL Herceptin reduced Ang-2 mRNA 90% (P
      <.001). Five of 11 cancers expressed both HER2 and Ang-2; 2 cancers expressed
      only Ang-2. CONCLUSIONS: We conclude that human breast cancers express Ang-2.
      HER2 signaling appears to regulate Ang-2 expression, although other signaling
      pathways may also regulate Ang-2. Ang-2 may be a therapeutic target in these
      cancers and may define which patients would benefit from Herceptin therapy.

PMID- 10922986
TI  - A central role for CD95 (Fas) in T-cell reactivity after injury.
AB  - BACKGROUND: Recent findings indicate that severe injury primes the immune system
      for an enhanced and lethal proinflammatory cytokine response against bacterial
      derived superantigens. This study asked whether this response to injury involves
      the CD95 (Fas) signaling pathway. METHODS: To assess superantigen-mediated
      mortality, wild-type (WT) C57BL/6 and Fas-deficient C57BL/6 lpr (-/-) (lpr) mice
      underwent burn or sham injury and were challenged 2 hours later with
      staphylococcal enterotoxin B (SEB). Spleen cells from sham and burn WT or lpr
      mice were stimulated in vitro with SEB to assess injury effects on IL-2, TNF
      alpha, and IFN-gamma production. RESULTS: Lpr burn mice survived the SEB
      challenge (100% survival), while WT burn mice showed a high mortality (17%
      survival, P < 001, analysis of variance [ANOVA]). Sham lpr or WT mice suffered no
      mortality to the SEB challenge. In vitro studies demonstrated that burn lpr mice
      produced significantly less TNF-alpha, IFN-gamma, IL-2 than burn WT mice (P <.01,
      ANOVA). Burn injury markedly enhanced SEB-stimulated IFN-gamma production by WT
      spleen cells and CD8+ T cells, while this did not occur in SEB-stimulated lpr
      spleen cells. CONCLUSIONS: These findings support the hypothesis that the CD95
      (Fas) signaling pathway plays an integral role in the injury-induced enhanced and
      lethal T-cell reactivity against bacterial superantigens.

PMID- 10922987
TI  - Bax is required for increased enterocyte apoptosis after massive small bowel
      resection.
AB  - BACKGROUND: Massive small bowel resection (SBR) increases rates of both
      enterocyte proliferation and apoptosis. Previous studies have demonstrated
      increased intestinal expression of proapoptotic bax mRNA and protein, as well as
      the appearance of an 18-kd bax cleavage product within 12 hours of SBR. This
      study tested the hypothesis that bax is required for postresection increases in
      enterocyte apoptosis. METHODS: Male bax-null and C57Bl/6 (control) mice underwent
      either a 50% proximal SBR or sham operation. After 3 days, the remnant ileum was
      harvested and weighed. Apoptotic indexes, proliferation indexes, villus heights,
      and crypt depths were determined. RESULTS: The usual adaptive increases in ileal
      wet weight, crypt depth, and rate of proliferation occurred in both the control
      and bax-null mice. Resection significantly increased the rate of apoptosis in the
      control mice; however, it failed to alter the apoptotic index in the bax-null
      mice. CONCLUSIONS: Bax is necessary for the increase in apoptosis that occurs
      after SBR, but its absence has no significant effect on short-term adaptation.
      These findings suggest that enterocyte proliferation and apoptosis are
      differentially regulated during intestinal adaptation.

PMID- 10922988
TI  - Suppression of PMN apoptosis by hypoxia is dependent on Mcl-1 and MAPK activity.
AB  - BACKGROUND: Hypoxia has been shown to delay the onset of neutrophil
      (polymorphonuclear leukocytes [PMNs]) apoptosis. With the use of antisense
      oligonucleotides, we have previously demonstrated that Mcl-1 is necessary for
      this effect. We wanted to further characterize the expression of Mcl-1 and
      examine signaling pathways required for the delay in apoptosis that is mediated
      by hypoxia. METHODS: For kinase signaling inhibition, PMNs were incubated for 12
      hours with the following inhibitors: PD98059 Mitogen Activated Protein Kinase
      Kinase (MEK), SB202190 (p38 mitogen-activated protein kinase [MAPK]), and
      LY294002 (phosphatidyl inositol-3-kinase [PI3K]). PMNs that were treated with
      inhibitors were assessed for apoptosis by morphologic features or were lysed for
      Western blot analysis. RESULTS: Western blot analyses, immunofluorescent
      staining, and quantification showed an upregulation of Mcl-1 expression after 12
      hours of incubation in response to hypoxia. When inhibitors of either MEK or p38
      MAPK were incubated with PMNs during hypoxia, apoptosis increased to similar
      levels as normoxia. We further wanted to determine whether signaling through p38
      MAPK or MEK led to increased Mcl-1 expression. Western blot analysis confirmed
      that the inhibition of p38 MAPK led to a significant decrease in Mcl-1
      expression. CONCLUSIONS: We have documented a novel mechanism by which hypoxia
      can modify PMN apoptosis in the wound site by the activation of p38 MAPK
      signaling, thereby inducing the anti-apoptotic protein Mcl-1.

PMID- 10922989
TI  - All-trans-retinoic acid decreases cell proliferation and increases apoptosis in
      an animal model of vein bypass grafting.
AB  - BACKGROUND: We have previously demonstrated a decrease in intimal hyperplasia in
      vein bypass grafts from animals treated with all-trans-retinoic acid (atRA). The
      purpose of this study was to examine the effect of atRA on proliferation and
      apoptosis rates in healing vein bypass grafts. METHODS: Interposition jugular
      vein bypass grafts were placed in the carotid artery of 30 New Zealand white
      rabbits. Animals received either atRA (10 mg/kg/d) or vehicle (corn oil) for a
      period of 2 weeks. Animals were killed at 3, 7, or 28 days after graft placement
      after having received 3 doses of 5-bromo-2'-?Deoxyuridine (BRDU, 35 Mg/KG).
      Animals Were Perfusion Fixed, And Vein Grafts Were Prepared For
      Immunohistochemistry By Using Antibodies To Brdu, Proliferating Cell Nuclear
      Antigen, And Bcl-XL. Apoptosis Was Measured By Using The Tunel Assay. Histologic
      Sections Were Analyzed By A Pathologist Blinded To The Study, And An Index Of
      Positively Stained Cells Was Generated For Each Layer Of The Vein Graft Wall.
      RESULTS: All-trans-retinoic acid reduced the proliferation index in the neointima
      of vein grafts during the first week after surgery. Apoptotic rates were higher
      in the intima of vein grafts from animals treated with atRA, which could not be
      explained by changes in bcl-xl expression. No differences were noted in the media
      or adventitia between the groups. CONCLUSIONS: atRA decreased cell proliferation
      and increased apoptosis in the intima of healing vein bypass grafts. These
      effects contribute to decreased intimal hyperplasia, which has been previously
      noted.

PMID- 10922990
TI  - Regulation of coronary myoplasmic Ca(2+)-myosin light chain phosphorylation
      pathway and vasomotor tone: hyperpolarizing versus depolarizing cardioplegia.
AB  - BACKGROUND: This study was designed to compare the effects of hyperpolarizing
      versus depolarizing cardioplegic solutions on the coronary vasomotor regulation,
      specifically focusing on coronary myoplasmic Ca2+-myosin light chain (MLC)
      phosphorylation pathway and beta-adrenergic signal transduction. METHODS: With
      the use of an in vitro cardioplegic model, rat coronary microvessels loaded with
      fura-2 were subjected to simulated cold (20 degrees C) cardioplegia and
      reperfused with Krebs solution for 60 minutes at 37 degrees C. Cardioplegia
      consisted of either (1) Krebs solution alone (control), (2) Krebs plus adenosine
      triphosphate-sensitive potassium channel opener (100 micromol/L pinacidil [PCO
      CP]), (3) hyperkalemic cardioplegia (K(+) = 25 mmol/L [K-CP]), or (4) K-CP plus
      magnesium (Mg(2+) = 25 mmol/L; [K/Mg-CP]). RESULTS: At the endpoint of the
      cardioplegic period, K-CP resulted in a significant increase both in [Ca(2+)](i)
      and in MLC phosphorylation compared with control (both P <.05). In contrast, PCO
      CP did not make any significant difference in these indices compared with
      control. After reperfusion, the relaxation responses to isoproterenol and
      forskolin after K-CP were significantly reduced (both P <.05 vs control) but were
      preserved after PCO-CP. K/Mg-CP provided comparable effects to PCO-CP.
      CONCLUSIONS: These results suggest that neither an activation of the coronary
      myoplasmic Ca(2+)-MLC phosphorylation pathway nor beta-adrenergic desensitization
      seen after exposure to depolarizing cardioplegia occurs with exposure to
      hyperpolarizing cardioplegia and magnesium-supplemented depolarizing hyperkalemic
      cardioplegia.

PMID- 10922991
TI  - The effect of protein kinase C and its alpha subtype on human vascular smooth
      muscle cell proliferation, migration and fibronectin production.
AB  - BACKGROUND: Vascular smooth muscle cell (SMC) migration, proliferation and
      extracellular matrix protein production are key steps in the formation of intimal
      hyperplasia, a process that leads to failure of vascular reconstructions. Protein
      kinase C (PKC) may be involved in all 3 cellular events. PKC consists of a family
      of 11 isotypes, 8 of which we have identified in human vascular SMCs. In this
      study we evaluate the role of PKCalpha as a second messenger for proliferation,
      migration and fibronectin production induced by human saphenous vein SMCs.
      METHODS: DNA synthesis was evaluated by using (3)H-thymidine incorporation.
      Mitogen-activated protein kinase (MAP-K) activation was quantified by Western
      blotting with an antibody to its phosphorylated substrate, Elk-1. Chemotaxis was
      evaluated by using a microchemotaxis chamber. SMC fibronectin was measured by
      Western blotting. For all experiments, PKCalpha was blocked with a selective
      inhibitor, Go6976. RESULTS: Go6976, at concentrations that allow selective
      inhibition of PKCalpha, inhibited platelet-derived growth factor-stimulated SMC
      proliferation and MAP-K activation by 30% to 40% and 30% to 60%, respectively.
      SMC chemotaxis was stimulated approximately 2-fold by the PKCalpha inhibitor.
      Neither basal nor transforming growth factor-betaI induced fibronectin production
      was affected by Go6976. CONCLUSIONS: Our data suggest that PKCalpha is a positive
      mediator of SMC proliferation and MAP-K activity, a negative regulator of
      migration and has no effect on SMC fibronectin production. These data suggest
      that modulating activities of specific PKC isotypes might be useful in both the
      study and control of intimal hyperplasia.

PMID- 10922993
TI  - Intrathymic alloantigen-mediated, tolerant, completely major histocompatibility
      complex-mismatched mouse hearts are specifically rejected by adoptively
      transferred anti-class I L(d+)-specific 2C cells.
AB  - BACKGROUND: Tolerance to cardiac allografts can be induced in mice and rats by
      the injection of donor alloantigen into the thymus in combination with a CD4 T
      cell-depleting antibody. CD8(+) cells in these animals are hyporesponsive to
      graft-specific alloantigens. Most of the CD8(+) T cells in the transgenic 2C
      mouse express a T-cell receptor specific for the class I major histocompatibility
      complex L(d+) locus. This study was designed to determine whether the adoptive
      transfer of these 2C T cells could precipitate rejection of a tolerant,
      completely major histocompatibility complex-mismatched L(d+) or L(d-) heart.
      METHODS: C57BL/6 mice (L(d-)) were given 10 x 10(6) cells of BALB/c (L(d+)) or
      dm2 (BALB/c background lacking L(d) [L(d-)]) splenocytes intrathymically and GK1.
      5 (10 mg/kg) intraperitoneally. Twenty-one days later, BALB/c or dm2 hearts were
      transplanted. On the day of transplantation or after long-term allograft
      acceptance, recipients received naive 2C cells or 2C cells sensitized by in vitro
      mixed lymphocyte culture with BALB/c (L(d+)). RESULTS: Mean survival time of
      BALB/c cardiac allografts in untreated C57BL/6 mice was 7.3 days, although 73% of
      the mice that were pretreated with BALB/c splenocytes IT plus GK1.5 accepted the
      donor antigen-specific heart allografts indefinitely. All recipients that were
      pretreated with the intrathymic plus GK1.5 and that were injected with naive 2C
      cells at the time of heart transplantation experienced rejection of the BALB/c
      (L(d+)), but not the dm2 (L(d-)) hearts. In contrast, naive 2C cells could not
      reject tolerant (>30 days acceptance) BALB/c (L(d+)) hearts. 2C cells sensitized
      in vitro against L(d) were able to reject established BALB/c hearts but could not
      reject the L(d-) dm2 hearts. CONCLUSIONS: L(d)-specific 2C T-cell receptor
      transgenic T cells that are adoptively transferred to recipients will precipitate
      the rejection of accepted hearts that express class I L(d+) in mice rendered
      tolerant by an intrathymic injection of alloantigen plus anti-CD4 monoclonal
      antibodies.

PMID- 10922992
TI  - Hypertonic saline solution induces prostacyclin production by increasing
      cyclooxygenase-2 expression.
AB  - BACKGROUND: Previously, we demonstrated that hypertonic saline solution (HTS) and
      endotoxin (lipopolysaccharide [LPS]) induce prostacyclin (PGI(2)) production in
      human endothelial cells. Here, we hypothesized that HTS and LPS may induce PGI(2)
      production by increasing cyclooxygenase (COX) expression. We further examined the
      activation of p38 and extracellular signal-regulated kinases (ERK) and questioned
      whether these transduction cascades might mediate COX expression. METHODS: Human
      umbilical vein endothelial cells were stimulated with varying concentrations of
      NaCl or LPS. RESULTS: HTS and LPS induced prompt activation of both p38 and ERKs
      that peaked at 30 minutes. HTS and LPS also induced a dose-related increase in
      COX-2 with maximal expression within 4 to 6 hours; there was no change in COX-1.
      This correlated with an increase in supernatant PGI(2) levels, which became
      statistically significant for NaCl of more than 40 mmol/L and for all LPS doses.
      The inhibition of p38 with SB202190 abrogated the osmotic and LPS-induced COX-2
      expression and PGI(2) production. Inhibition of ERK activation had no effect on
      COX-2 expression. CONCLUSIONS: Hyperosmolarity and LPS induce, in chronologic
      order, p38 and ERK activation, COX-2 expression, and PGI(2) production. Because
      COX is the rate-limiting enzyme in prostaglandin synthesis, it is likely that the
      increase in PGI(2) production is due to, at least in part, the increased COX-2
      expression. The data also suggest that p38 mitogen-activated protein kinase is
      involved in the signaling cascade for COX-2 expression.

PMID- 10922994
TI  - Regional muramyl tripeptide phosphatidylethanolamine administration enhances
      hepatic immune function and tumor surveillance.
AB  - BACKGROUND: Immune status of the liver may affect growth of liver metastases. We
      analyzed the ability of muramyl tripeptide phosphatidylethanolamine (MTP-PE), an
      immunomodulatory bacterial cell wall analog, to stimulate Kupffer cells (KCs) and
      protect against tumor growth, with or without an immunosuppressive partial
      hepatectomy (PH). Impact of MTP-PE's route of administration on KC function was
      assessed. METHODS: Buffalo rats (n = 7 to 12/group) were treated with saline, 40
      microg MTP-PE intraportally (portal) or intravenously (IV) and challenged with 5
      x 10(5) hepatoma cells, and tumors counted on day 21. To assess MTP-PE's impact
      on KC stimulation in animals undergoing PH, a known stimulant of tumor cell
      growth, groups were treated with saline or MTP-PE and challenged with tumor and
      underwent 30% PH. KCs were harvested and analyzed for superoxide production.
      Statistical analysis was performed with Mann-Whitney U test or chi-square test.
      RESULTS: MTP-PE-treated animals had fewer tumor nodules than control animals (19
      vs 184, P <.005). MTP-PE-portal animals had fewer nodules than MTP-PE-IV (2 vs
      36, P <.05). MTP-PE treatment before PH resulted in fewer tumor nodules compared
      with control animals (192 vs 276, P <. 05). MTP-PE administration increased
      macrophage superoxide production (20.6 +/- 2 vs 11.9 +/- 1.1 nmol/10(6) cells, P
      <.005). CONCLUSIONS: MTP-PE improved KC function and decreased growth of
      microscopic tumor cells. MTP-PE's effects persist after an immunosuppressive
      hepatectomy. Portal administration was the most effective. MTP-PE administration
      may be useful as a neoadjuvant therapy for patients undergoing resection of liver
      malignancies.

PMID- 10922995
TI  - Interleukin-4 regulates macrophage interleukin-12 protein synthesis through a c
      fos mediated mechanism.
AB  - BACKGROUND: Interleukin-4 (IL-4) treatment after lipopolysaccharide (LPS)
      induction inhibits macrophage (Mphi) IL-12 synthesis; however, IL-4 pretreatment
      (PreTx) primes the Mphi for increased LPS-induced IL-12 production. In this study
      we study the role of c-fos in the IL-4 priming of Mphi IL-12 synthesis. METHODS:
      With a murine in vitro peritoneal M phi model, we studied the effect of either c
      fos deficiency (wild type, WT; homozygous c-fos knockout, Homo KO) or c-fos
      overexpression to study the role of c-fos in IL-4 priming of LPS-induced M phi IL
      12 synthesis. RESULTS: (1) We first show that IL-4 PreTx results in a 72%
      decrease in Mphi c-fos mRNA compared with vehicle PreTx. (2) With respect to IL
      12 p70 protein, IL-4 PreTx in the WT group increased LPS-induced Mphi IL-12 p70
      2.2-fold compared with vehicle PreTx. Compared with vehicle PreTx in the WT
      group, vehicle PreTx in the Homo KO group followed by LPS stimulation resulted in
      a 2.8-fold increase in IL-12 p70 in the Homo KO group. IL-4 PreTx did not
      significantly increase IL-12 p70 over vehicle PreTx in the Homo KO group. (3) We
      studied the effect of c-fos overexpression on LPS-induced Mphi IL-12 production
      when primed with IL-4. Overexpression of c-fos completely inhibited IL-4 primed
      LPS-induced IL-12 p70 protein synthesis. CONCLUSIONS: These data demonstrated
      that down-regulation of c-fos is an integral part of the IL-4 priming process for
      Mphi IL-12 production.

PMID- 10922996
TI  - Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory
      kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome.
AB  - BACKGROUND: Select pancreatic enzymes, primarily elastase, precipitate pulmonary
      injury similar to pancreatitis-associated adult respiratory distress syndrome and
      stimulate leukocyte cytokine production in vitro via nuclear factor kappa B (NF
      kappaB) activation. This study explores the effect of systemic pancreatic enzymes
      on pulmonary NF-kappaB and inhibitory kappa B (IkappaB) proteins and their role
      in enzyme-induced pulmonary injury. METHODS: Mice received pancreatic elastase,
      amylase, lipase, or trypsin intraperitoneally. Bronchoalveolar lavage
      IkappaBalpha/IkappaBbeta proteins were measured by immunoblot. Pulmonary NF
      kappaB activation, tumor necrosis factor (TNF) gene expression, and neutrophil
      infiltration (myeloperoxidase) were determined and myeloperoxidase experiments
      repeated in p55 TNF receptor-deficient (TNF KO) animals. Additional animals
      received pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB
      activation, and TNF protein and pulmonary microvascular permeability were
      measured after elastase administration. RESULTS: Pancreatic elastase induced
      pulmonary IkappaBalpha/IkappaBbeta degradation (30 minutes), NF-kappaB activation
      (60 minutes), and TNF gene expression (60 minutes) with subsequent neutrophilic
      inflammation (4 hours) and microvascular leakage (24 hours), whereas amylase,
      lipase, and trypsin did not. Furthermore, lung injury was markedly reduced in TNF
      KO animals and PDTC significantly attenuated TNF production and pulmonary
      microvascular leakage. CONCLUSIONS: Pancreatic elastase induces cytokine-mediated
      lung injury and this pathway involves the NF-kappaB second messenger system,
      further supporting elastase as a factor linking pancreatic inflammation to
      systemic illness during severe acute pancreatitis.

PMID- 10922997
TI  - Substance P is a determinant of lethality in diet-induced hemorrhagic
      pancreatitis in mice.
AB  - BACKGROUND: The neuropeptide substance P (SP) induces plasma extravasation and
      neutrophil infiltration by activating the neurokinin 1-receptor (NK1-R). SP
      induced neurogenic inflammation is terminated by the cell surface enzyme neutral
      endopeptidase (NEP), which degrades SP. We determined whether genetic deletion of
      the NK1-R reduces mortality and, conversely, whether genetic deletion of NEP
      increases mortality in a lethal model of hemorrhagic pancreatitis. METHODS:
      Necrotizing pancreatitis was induced by feeding mice a diet deficient in choline
      and supplemented with ethionine. We determined the length of survival, the
      severity of pancreatitis (by measuring the neutrophil enzyme myeloperoxidase
      [MPO] and by histologic evaluation), and the severity of pancreatitis-associated
      lung injury (lung MPO and histology) in NK1-R (+/+)/(-/-) and NEP (+/+)/(-/-)
      mice. RESULTS: Genetic deletion of the NK1-R significantly improved survival
      (100% vs 8% at 120 hours, P <.001) and reduced pancreatic MPO and acinar cell
      necrosis. Conversely, genetic deletion of NEP significantly worsened survival (0%
      vs 90% at 120 hours, P <.001) and exacerbated pancreatic MPO and pancreatitis
      associated lung injury. CONCLUSIONS: Substance P is an important determinant of
      lethality in this model of necrotizing pancreatitis. Defects in NEP expression
      could lead to uncontrolled inflammation.

PMID- 10922998
TI  - Nitric oxide is a neurotransmitter in the chloride secretory response to
      serotonin in rat colon.
AB  - BACKGROUND: Serotonin (5-hydroxytryptamine [5-HT]) has been shown to induce
      chloride secretion through a nonadrenergic/noncholinergic neural pathway,
      mediated by a 5-HT(3) receptor. We hypothesized that 5-HT(3)-induced Cl(-)
      secretion is ultimately mediated by nitric oxide (NO). METHODS: Unstripped sheets
      of rat distal colon were mounted in Ussing chambers and short-circuited. The 5
      HT(3) receptor agonist, 2-methyl-5-HT, was added in the absence and presence of
      the NO synthase inhibitor, L-NAME. Companion studies involved the addition of
      sodium nitroprusside to tissue that was incubated with or without tetrodotoxin.
      RESULTS: L-NAME caused a significant reduction in the 2-methyl-5-HT-induced
      change in circuit current, in a concentration-dependent manner. Sodium
      nitroprusside caused a change in circuit current over baseline in 5 minutes. The
      addition of tetrodotoxin did not significantly alter the change in circuit
      current; however, the apical Cl(-) channel blocker, anthracene-9-carboxylic acid,
      abolished this response. CONCLUSIONS: Neurally mediated Cl(-) secretion in
      response to 2-methyl-5-HT is inhibited by an NO synthase inhibitor. Exogenous NO
      mimics this response, which is unaffected by tetrodotoxin. These data suggest
      that neurally mediated serotoninergic Cl(-) secretion is, in part, mediated by
      NO. The ability of exogenous NO to induce a change in circuit current in the
      presence of tetrodotoxin suggests that NO is a final neurotransmitter in this
      neural-mucosal reflex and therefore acts directly on the enterocyte to induce
      secretion.

PMID- 10923000
TI  - What influences medical students' choice of surgical careers.
AB  - BACKGROUND: Recent emphasis in medical education has been to encourage students
      to pursue primary care careers. This could have a negative impact on applications
      to surgical residencies. METHODS: To determine what factors are most influential
      for a student to pursue a surgical career in spite of this environment, third-
      and fourth-year medical students were surveyed with a 40-item questionnaire.
      RESULTS: The response rate was 37% (76/205). Those students considering a career
      in surgery were more likely than their counterparts to be motivated by role
      models (P <.006), career opportunities (P <.006), and academic opportunities (P
      <.013) in surgery. They were less likely than their counterparts to be
      discouraged from surgery on the basis of lifestyle (P <.001), time commitment (P
      <.001), call schedules (P <.001), or residency length (P <.028). No differences
      regarding financial rewards, research opportunities, or intellectual challenges
      were seen between the groups. Neither race nor sex had a significant role in the
      selection of surgery as a career. CONCLUSIONS: The data suggests that students
      are more likely to be influenced to pursue surgical careers by offering early
      exposure to positive role models and career and academic opportunities in
      surgery. Knowledge of these influences on student career choices should help
      surgical educators attract and maintain student interest in surgical careers.

PMID- 10922999
TI  - Insight into the mechanism by which estradiol improves organ functions after
      trauma-hemorrhage.
AB  - BACKGROUND: Recent studies have indicated that female rodents with high levels of
      estradiol (proestrus) have better organ functions after trauma-hemorrhage than
      females with low estradiol levels (estrus) or male animals. However, the precise
      role of estrogens in maintaining organ function after hemorrhage remains unknown.
      METHODS: Adult female Sprague-Dawley rats were ovariectomized 14 days before the
      experiment to decrease circulating levels of estradiol. Animals underwent
      laparotomy to induce tissue trauma and were then bled to and maintained at a mean
      arterial pressure of 40 mm Hg until 40% of the maximal bleed-out volume was
      returned in the form of Ringer's lactate. Resuscitation was carried out with 4
      times the volume of maximal bleed-out with Ringer's lactate during a period of 1
      hour. 17beta-Estradiol (E2, 1 mg/kg body weight intravenously) with or without a
      specific estrogen receptor antagonist ICI 182,780 (3 mg/kg body weight
      intraperitoneally) was given at the beginning of resuscitation. At 24 hours after
      hemorrhage and resuscitation, cardiovascular and hepatocellular functions (ie,
      the maximal velocity and overall efficiency of indocyanine green clearance) were
      determined. Plasma E2 was also assayed. The effects of ovariectomy and E2
      administration on uterine weight were measured in additional groups of animals.
      RESULTS: The results indicate that cardiovascular and hepatocellular organ
      functions were significantly depressed after trauma-hemorrhage and were restored
      in animals receiving E2. However, simultaneous administration of its specific
      receptor antagonist abolished the salutary effects of E2 treatment despite high
      circulating levels of E2. Uterine weight decreased at 14 days after ovariectomy,
      which was partially restored with a single dose of E2. CONCLUSIONS:
      Administration of 17beta-estradiol should be considered a novel and safe adjunct
      for ameliorating hemorrhage-induced organ dysfunctions in ovariectomized and
      postmenopausal women because of their low estradiol levels.

PMID- 10923001
TI  - Editorial: what influences medical students' choice of surgical careers- a
      critical appraisal

PMID- 10923002
TI  - Burn-activated neutrophils and tumor necrosis factor-alpha alter endothelial cell
      actin cytoskeleton and enhance monolayer permeability.
AB  - BACKGROUND: This study examined the hypothesis that exposure of an endothelial
      cell (EC) monolayer to tumor necrosis factor-alpha (TNF-alpha) and that burn
      activated neutrophils alter EC actin cytoskeleton and enhance the permeability of
      the monolayer. METHODS: Neutrophils were harvested from rats that had undergone a
      45% surface area burn (BURN-neutrophil) or uninjured control rats. ECs were grown
      on polyester filters or fibronectin-coated glass slides and exposed for 4 hours
      to media, TNF-alpha (100 ng/mL), or TNF-alpha plus BURN-neutrophil or uninjured
      control rats (10(7) cells). Monolayer permeability was assessed by measuring the
      flux of albumin across the cells. EC surface area and microfilament number and
      length were determined by the staining of actin microfilaments with rhodamine
      phalloidin followed by fluorescent microscopy. RESULTS: The amount of albumin
      that moved across the monolayer in response to TNF-alpha plus BURN-neutrophil was
      twice that of media alone (P <.05) or TNF-alpha alone (P <.05). The number and
      length of actin microfilaments in ECs exposed to TNF-alpha plus BURN-neutrophil
      were significantly less than that of cells exposed to media alone or TNF-alpha
      alone. CONCLUSIONS: These data are consistent with a hypothesis that TNF-alpha
      plus BURN-neutrophil affect endothelial monolayer permeability by altering EC
      actin cytoskeletal organization.

PMID- 10923003
TI  - Short-term tracheal occlusion corrects pulmonary vascular anomalies in the fetal
      lamb with diaphragmatic hernia.
AB  - BACKGROUND: Sustained fetal tracheal occlusion (TO) results in accelerated lung
      growth but causes severe type II cell depletion. Temporary TO fails to cause lung
      growth in a congenital diaphragmatic hernia (CDH) model but preserves type II
      cells and corrects pulmonary hypertension. Herein, we study the pulmonary
      vascular changes caused by temporary TO. METHODS: CDH was created in 12 fetal
      lambs (65-70 d; term, 145 days). In 6 lambs, the trachea was occluded for 2 weeks
      (CDH + TO; 108-122 d). Animals were killed at 136 days. The lungs were processed
      with elastin stains and anti-alpha-smooth muscle actin antibody. Partial or
      circumferential presence of inner and outer elastic lamina was used to determine
      muscularization of pulmonary arterioles. The percent of medial wall thickness was
      plotted against vessel diameter for each group. RESULTS: Lung weight/body weight
      was smaller in lambs with CDH (1. 35% +/- 0.56%) and CDH + TO (1.70% +/- 0.34%)
      than in control lambs (3.55% +/- 0.56%; P <.05, single-factor analysis of
      variance). The smallest muscularized vessel was 113 +/- 50 microm, and the
      largest nonmuscularized vessel was 138 +/- 49 microm in lambs with CDH,
      significantly different from control lambs (185 +/- 69 microm and 350 +/- 116
      microm, respectively) and lambs with CDH + TO (185 +/- 97 microm and 245 +/- 100
      microm, respectively; P <.05). In lambs with CDH, only 25% of vessels of less
      than 60 microm were nonmuscularized, compared with 81% in control lambs (P <.05)
      and 74% in lambs with CDH + TO.Conclusions. Temporary tracheal occlusion, from
      108 to 122 days, corrects the abnormal muscularization of pulmonary arterioles
      seen in CDH. These morphometric findings parallel physiologic results at birth
      and further suggest that short-term occlusion, which preserves surfactant
      producing type II pneumocytes without lung growth, may be sufficient to improve
      neonatal outcome of diaphragmatic hernia.

PMID- 10923004
TI  - Immunization with DNA coding for gp100 results in CD4 T-cell independent
      antitumor immunity.
AB  - BACKGROUND: Xenogeneic DNA immunization can exploit small differences in
      expressed protein sequence resulting in immune recognition of self-molecules. We
      hypothesized that immunizing mice with xenogeneic DNA coding for the human
      melanosomal membrane glycoprotein gp100 would overcome immune ignorance or
      tolerance and result in tumor immunity. We also investigated the immunologic
      mechanisms of the antitumor immunity. METHODS: C57BL/6 mice were immunized with
      DNA coding for human gp100, mouse gp100, or control vector by gene gun. After
      immunization, mice were challenged with a syngeneic melanoma expressing gp100,
      and tumor growth was analyzed. Mice deficient in major histocompatibility complex
      class I or class II molecules were similarly studied to assess the immunologic
      mechanism of the tumor protection. RESULTS: There was significant tumor
      protection after vaccination with xenogeneic human gp100 DNA. Class I, but not
      class II, major histocompatibility complex molecules were required for tumor
      immunity. In addition, mice immunized with human gp100 demonstrated autoimmunity
      manifested as coat color depigmentation. CONCLUSIONS: Immunization with
      xenogeneic DNA coding for the melanosomal glycoprotein gp100 results in tumor
      protection and autoimmune depigmentation. These results show that xenogeneic DNA
      vaccines can lead to cancer immunity without CD4(+) T-cell help with potential
      implications for rational vaccine design.

PMID- 10923005
TI  - Cytochrome P450 polymorphisms are associated with reduced warfarin dose.
AB  - BACKGROUND: Warfarin use is complicated by an erratic dose response. Interpatient
      variability associated with warfarin therapy may be partly attributable to
      polymorphisms of the cytochrome P450 (CYP) complex. The purpose of this study was
      to ascertain the frequency and influence of CYP polymorphisms on warfarin dosing
      in our patient population. METHODS: Patients receiving warfarin therapy were
      recruited from the inpatient divisions of our hospital. Genotyping for known
      polymorphic alleles of the CYP subfamilies CYP2C9 (CYP2C9*1, CYP2C9*2, and
      CYP2C9*3) and CYP2A6 (CYP2A6*1, CYP2A6*2) with the use of standard methods of
      polymerase chain reaction amplification was performed. An unpaired t test was
      used to statistically compare genotypes. RESULTS: Genotype frequency in 38
      patients is as follows: CYP2C9*1/CYP2C9*1, 71%; CYP2C9*1/CYP2C9*2, 21%;
      CYP2C9*2/CYP2C9*2, 3%; CYP2C9*1/CYP2C9*3, 5%; CYP2A6*1/CYP2A6*1, 95%;
      CYP2A6*1/CYP2A6*2, 5%. Compared to a wild-type genotype, the presence of the
      CYP2C9*2, CYP2C9*3, or CYP2A6*2 allele was associated with a significant
      reduction in weekly warfarin dose (mean weekly warfarin dose [+/- SE] for wild
      type genotype was 0.397 +/- 0.024 mg/kg/wk vs 0.307 +/- 0.03 mg/kg/wk for
      carriers of CYP2C9*2, CYP2C9*3, or CYP2A6*2 polymorphism; P =.03). CONCLUSIONS:
      Polymorphisms that impair warfarin metabolism are common, occurring in 34% of
      patients, and are associated with increased warfarin sensitivity. The use of
      genotypic information to prescribe more accurate doses of warfarin may increase
      the safety and efficacy of this medication.

PMID- 10923006
TI  - Does the participation of a surgical trainee adversely impact patient outcomes? A
      study of major pancreatic resections in California.
AB  - BACKGROUND: Some patients have concerns regarding the impact of surgical trainees
      on the quality of care that they receive in teaching hospitals. No population
      based data exist that describe outcomes of surgical procedures in teaching and
      nonteaching hospitals; however, institutional data suggest that teaching
      hospitals provide high-quality care. We hypothesized that the presence of a
      general surgery residency program (GSRP) is associated with superior outcomes for
      pancreatic resection, a complex surgical procedure. METHODS: A retrospective,
      population-based, risk-adjusted analysis of 5696 patients who underwent major
      pancreatic resection compares the outcomes of patients treated at hospitals with
      a GSRP (GSRP+) and those hospitals without a GSRP (GSRP-). RESULTS: GSRP+
      hospitals had a lower operative mortality rate (8.3% vs 11.0%; P <. 001), a lower
      percentage of patients discharged to another acute care hospital or skilled
      nursing facility (6.5% vs 13.0%; P <.001), and a longer length of stay compared
      with GSRP- hospitals (22.1 +/- 0.4 days vs 19.6 +/- 0.3 days; P <.001). The
      observed difference in hospital mortality rates was not significant after an
      adjustment was made for patient mix and hospital volume (9.7% vs 10.0%). However,
      superior outcomes were found in the university teaching hospitals, as compared
      with the affiliated teaching and the nonteaching hospitals (5.3% [P <.001] vs
      11.4% vs 11.0%; risk adjusted, 8.0% [P <.05] vs 10.9% vs 10.0%). CONCLUSIONS: The
      presence of surgical trainees does not have an adverse impact on the quality of
      care for One complex procedure, pancreatectomy, and is associated with superior
      operative mortality rate in university teaching hospitals.

PMID- 10923007
TI  - Predictors of health after revascularization for extremity ischemia.
AB  - BACKGROUND: To assess the impact of surgical revascularization for lower
      extremity ischemia, we determined (with the use of the SF-36 health survey) the
      functional health status of patients who underwent either inflow or outflow
      procedures. METHODS: The SF-36 survey was given prospectively to 104 patients
      before operation and at intervals ranging from 10 days to 1 year after operation
      from January 1998 to July 1999. To determine whether revascularization was
      associated with improved patient health status, mean scores were compared before
      and after operation by univariate and multivariate analysis. To identify the
      factors that influenced patient health status, we performed multiple regression
      analysis to test the hypothesis that outcome is affected by age, gender, time
      since procedure, diabetes, indication, and inflow versus outflow procedure.
      RESULTS: There was a significant decrease in the general health score of patients
      before outflow bypass as compared with inflow procedure (45.3 +/- 5.3 versus 32.1
      +/- 3.3 [mean +/- SEM]; P <.05). After the procedure, only those patients who had
      undergone inflow procedures had improved outcome scores. Diabetes, outflow
      procedures, limb salvage as indication, and time since operation were determined
      by multiple regression affecting outcome scores to be significant factors.
      CONCLUSIONS: The SF-36 health survey demonstrated that diabetes, procedure type,
      indication, and time after procedure significantly affected the functional
      outcome for patients who were treated surgically for lower extremity ischemia.
      Despite successful revascularization, significant deficits in functional health
      remain in patients with lower extremity ischemia.

PMID- 10923008
TI  - Microsatellite marker of interferon-gamma receptor 1 gene correlates with
      infection following major trauma.
AB  - BACKGROUND: This study hypothesizes that predicted polymorphism of the interferon
      gamma receptor 1 gene may play an important role in infection after trauma as
      supported by microsatellite analysis. METHODS: DNA was extracted from the
      peripheral leukocytes of 38 trauma patients with Injury Severity Scores greater
      than 16. D6S471, a microsatellite marker on chromosome 6 near interferon-gamma
      receptor 1, was amplified with polymerase chain reaction, and genotypes were
      determined. RESULTS: The mean Injury Severity Score was 32, and 63% of patients
      (24 of 38) developed major infection. Three alleles and 5 genotypes were
      identified for D6S471. Twenty-six percent of patients (10 of 38) had genotype AA,
      all of whom developed major infection (P =.004). Genotype BB accounted for 57% of
      the uninfected population (8 of 14) but only 21% of the infected group (P =.028).
      Allele A had a frequency of 33%, of which 22 alleles (88%) were found in infected
      patients (P =.001). In addition, allele B accounted for 61% of the uninfected
      group (17 of 28) but only 23% (11 of 48) of the infected group (P =.001). Allele
      C demonstrated no correlation. CONCLUSIONS: Microsatellite polymorphism
      correlates strongly with infection. These findings portend polymorphism in the
      receptor itself and thereby represent a genetic basis for the development of
      infection. We suggest this identifies a high-risk group who could benefit from
      more specific therapy that may have the potential to overcome this receptor
      insufficiency.

PMID- 10923009
TI  - How many lymph nodes are enough during sentinel lymphadenectomy for primary
      melanoma?
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy has been shown to reliably identify
      nodal metastases and the subsequent need for further surgical and adjuvant
      therapy in patients with cutaneous melanoma. Although SLN identification rates
      have improved with the addition of radioactive colloid to the blue dye technique,
      it remains unclear how many lymph nodes should be removed to accurately determine
      the histologic status of the nodal basin. The objective of this study was to
      determine the optimal extent of SLN biopsy in these patients. METHODS: The
      records of 633 consecutive patients with melanoma (765 nodal basins) whose
      primary treatment included SLN biopsy with the use of a combination of blue dye
      and technetium Tc 99 labeled sulfur colloid were reviewed. SLN biopsy consisted
      of the removal of all of the blue-stained nodes and all nodes with radiotracer
      uptake activity of at least twice background. RESULTS: SLN biopsy was successful
      in 765 of 772 basins (99%). A mean of 1.9 SLNs (median, 2 SLNs) per basin were
      excised. At least 3 SLNs were removed in 176 basins (23%). The overall histologic
      status of a basin was always established by the first or second SLN harvested
      (ie, in no patient was the third or subsequent SLN positive when 1 of the first 2
      was not). Of the 124 basins containing lymphatic metastases, the SLN that
      contained the maximal radiotracer uptake (hottest) and/or stained blue was
      pathologically positive in 118 basins (95%). In only 6 of the 124 positive basins
      (5%) was the sole evidence of occult nodal metastases identified in an SLN that
      was neither blue-stained nor the hottest. All but 1 of these SLNs had counts that
      were at least 66% of the hottest node in the basin. CONCLUSIONS: With a combined
      modality approach to SLN biopsy, removal of more than 2 SLNs did not provide
      information that upstaged any patient with primary melanoma. Removal of
      additional nonblue SLN(s) that contained radioactive counts of at least twice
      background but lower than two thirds of the SLNs with maximal radiotracer uptake
      affected patient management in less than 0.2% of all cases. These findings may be
      helpful in minimizing the extent of surgery and perhaps in reducing the costs and
      resource use associated with operating room time and pathologic examination.

PMID- 10923010
TI  - Persistence of muscle catabolism after severe burn.
AB  - BACKGROUND: The hypermetabolic response to severe burn is characterized by muscle
      protein catabolism. Current opinion states that the hypermetabolic state resolves
      soon after complete wound closure. Clinically, we have witnessed that burned
      children appear to be hypermetabolic and catabolic long after full healing of
      their wounds. Our goal in this study was to determine scientifically if burn
      associated hypermetabolism persists after full wound healing. METHODS: To
      determine the duration of muscle catabolism and systemic hypermetabolism after
      severe burn in children, patients with > 40% total body surface area burns were
      enrolled in a prospective, longitudinal study; resting energy expenditure was
      measured by indirect calorimetry, muscle protein kinetics were determined by
      using stable isotopic methodology, and body composition was measured by dual
      energy x-ray absorptiometry imaging. Data were collected at 6, 9, and 12 months
      after injury. RESULTS: The mean total body surface area burned was 65% +/- 13%,
      and the mean age was 7.6 +/- 1. 5 years. Resting energy expenditure was elevated
      above the predicted age-matched levels from the Harris-Benedict equation and
      incrementally declined throughout the 12-month study. The net protein balance and
      lean mass reflected catabolic persistence at 6 and 9 months after severe burn.
      Between 9 and 12 months, protein breakdown decreased, net protein balance
      improved, and lean body mass increased. CONCLUSIONS: In severely burned children,
      hypermetabolism and catabolism remain exaggerated for at least 9 months after
      injury. This suggests that therapeutic attempts to manipulate the catabolic and
      hypermetabolic response to severe injury should be continued long after injury.

PMID- 10923011
TI  - The macromolecular associations of heat shock protein-27 in vascular smooth
      muscle.
AB  - BACKGROUND: Behavioral stress is a risk factor for hypertension and
      atherosclerosis. Stress leads to increases in the expression and phosphorylation
      of heat shock proteins (HSPs) in vascular smooth muscle. Two small heat shock
      proteins, HSP27 and HSP20, have been implicated in the regulation of the
      contraction and relaxation of smooth muscle. We hypothesized that stress-induced
      alterations in the phosphorylation of HSP27 would effect the macromolecular
      associations of the small HSPs. METHODS: Bovine carotid artery smooth muscle was
      treated with buffer alone or with the chemical stressor, arsenite. HSP27
      phosphorylation was determined with isoelectric focusing immunoblotting.
      Macromolecular interactions were determined with subcellular fractionation,
      molecular sieving, and glutaraldehyde cross-linking and immunoblotting. RESULTS:
      Arsenite treatment led to increases in the phosphorylation of HSP27, a
      redistribution of some HSP27 from a cytosolic to a particulate fraction and to
      the formation of larger macromolecular aggregates of HSP27. Glutaraldehyde cross
      linking and immunoblotting demonstrated that HSP27 existed in monomeric and
      dimeric forms, which suggested that the large aggregates were not simply
      aggregates of HSP27 but contained other proteins. CONCLUSIONS: Cellular stress
      leads to increases in the phosphorylation of HSP27 and to changes in the
      macromolecular associations of HSP27 in intact vascular smooth muscles. The
      functions of the small HSPs in the vascular smooth muscle may be dependent on
      both phosphorylation and macromolecular associations.

PMID- 10923012
TI  - Endothelial selectin blockade attenuates lung permeability of experimental acid
      aspiration.
AB  - BACKGROUND: A central role for the polymorphonuclear leukocyte (PMN) in
      experimental acid aspiration has been demonstrated by the observation that PMN
      depletion reduced pulmonary vascular permeability. This study investigates the
      role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion
      protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating acid aspiration
      lung injury. METHODS: Tracheostomy tubes were placed in male C57BL/6 mice and 0.1
      N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of
      (125)I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN
      accumulation in the bronchoalveolar lavage fluid were assessed. RESULTS: PI in
      neutropenic mice was 63% reduced compared with the untreated group and similar to
      the PI of mice treated with 1 mg/kg rPSGL-Ig before acid aspiration. PMN count of
      19 +/- 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was
      significantly less than the untreated group PMN count of 586 +/- 72. The
      respective PI in mice treated with rPSGL-Ig (1/2) hour and 1 hour after acid
      aspiration was 45% and 39% reduced compared with the untreated group.
      CONCLUSIONS: Endothelial selectin blockade is as effective as PMN depletion in
      moderating acid aspiration induced lung permeability. Delayed antiselectin
      therapy can decrease lung injury.

PMID- 10923013
TI  - Liposomal antioxidants provide prolonged protection against acute respiratory
      distress syndrome.
AB  - BACKGROUND: We have previously shown that N-acetylcysteine (NAC), an antioxidant,
      in the resuscitation fluid after shock prevents lung injury in response to
      lipopolysaccharide (LPS) by inhibiting chemokine generation by alveolar
      macrophages in the lung. However, the protection was short-lived. We hypothesized
      that liposomal (Lip) NAC delivered intratracheally might be delivered directly to
      the target cells and exert prolonged effect. METHODS: Sprague-Dawley rats were
      bled to a blood pressure of 40 mm Hg for 1 hour and resuscitated with shed blood
      and equal volume of Ringer's lactate. In some studies 500 mg/kg NAC was included
      in the resuscitation fluid. Thirty minutes later, 150 microl LipNAC (9.4 mg/kg
      NAC) was given intratracheally. One hour and 18 hours after resuscitation, LPS
      (30 microg/kg) or saline was given intratracheally. Lung injury was assessed by
      permeability to (125)I-albumin, bronchoalveolar lavage neutrophils and lung
      myeloperoxidase. The cytokine-induced neutrophil chemoattractant (CINC)
      expression in the lung was assessed by Northern blot. RESULTS: At the early time
      point, both NAC and LipNAC protected the lung with the effects in significantly
      reducing the increases in transpulmonary albumin flux, neutrophil influx and
      myeloperoxidase in the lungs of shock/LPS rats. However, by the late time point,
      only LipNAC retained its salutary effect. This correlated well with persistent
      ability to prevent CINC increase. In addition, Lipalpha-tocopherol (alpha-T) and
      LipNAC/alpha-T were tested and determined to be effective to protect the lung.
      CONCLUSIONS: Liposomal encapsulation of antioxidants at low dose provides long
      lasting protection against acute respiratory distress syndrome after shock. This
      may represent a novel treatment approach.

PMID- 10923014
TI  - Bactericidal and endotoxin neutralizing activity of a peptide derived from
      Limulus antilipopolysaccharide factor.
AB  - BACKGROUND: Release of lipopolysaccharide (endotoxin, LPS) is a critical inciting
      event in the development of sepsis syndrome due to gram-negative bacteria, and
      mortality associated with this entity remains approximately 40%. Limulus anti-LPS
      factor (LALF) is a naturally occurring horseshoe crab derived protein that,
      unlike antibiotics, is both bactericidal for gram-negative bacteria and capable
      of neutralizing LPS. We hypothesized that a peptide derived from the active
      domain of LALF (LALF #28-54) would exhibit potent biologic activity similar to
      that of LALF itself and could potentially be useful as a therapeutic agent.
      METHODS: The effects of LALF, synthetic peptide LALF #28-54, polymyxin B (PmB),
      and a biologically inactive synthetic peptide were examined in several models. In
      vitro bactericidal activity was determined against Pseudomonas aeruginosa, and
      LPS-neutralizing capacity was determined via inhibition of LPS-induced tumor
      necrosis factor-alpha (TNF-alpha) secretion by RAW 264.7 cells. In vivo biologic
      activity was determined via pretreatment following which P aeruginosa endotoxemia
      or bacteremia was induced; serum TNF-alpha levels, bacterial clearance, and
      survival were assessed. RESULTS: LALF and LALF #28-54 exhibited potent in vitro
      bactericidal and LPS-neutralizing activity comparable to PmB (P <.01). However,
      although LALF #28-54 diminished systemic TNF-alpha production and aided bacterial
      clearance similar to that observed for LALF (P <.01), it did not provide
      significant protective capacity (P >.1). CONCLUSIONS: These data demonstrate that
      peptide LALF #28-54 retained the LPS-neutralizing and bactericidal biologic
      activity of LALF but failed to protect during overwhelming P aeruginosa
      bacteremia, perhaps due to short serum half-life.

PMID- 10923016
TI  - The cancer-associated Sm-like oncogene: a novel target for the gene therapy of
      pancreatic cancer.
AB  - BACKGROUND: The prognosis for pancreatic cancer (PC) remains dismal, providing a
      clear need for the development of novel therapies. We have previously shown that
      the cancer-associated Sm-like (CaSm) oncogene is overexpressed in the great
      majority of pancreatic tumors and is required to maintain the transformed
      phenotype. The purpose of this study was to determine whether the application of
      CaSm antisense gene therapy would generate a significant antitumor effect against
      PC. METHODS: An adenoviral vector (Ad-alphaCaSm) expressing a 900-base pair
      antisense RNA to CaSm was created. The PC cell lines AsPC-1 and Capan-1 were
      infected with this vector and examined for changes in in vitro proliferation by
      using methyl thiazol tetrazolium and soft agar assays. SCID-Bg mice bearing
      subcutaneous AsPC-1 tumors were treated with Ad-alphaCaSm (1 x 10(9) plaque
      forming units) as a single intratumor injection with tumor growth and survival
      monitored. RESULTS: AsPC-1 and Capan-1 cells showed decreased in vitro
      proliferation (93%, P =.0041, and 70%, P =. 0038, respectively) and anchorage
      independent growth (55%, P =.02, and 45%, P =.03, respectively) after treatment.
      Ad-alphaCaSm reduced in vivo AsPC-1 tumor growth by 40% (n = 10), extending
      median survival time from 35 to 60 days. CONCLUSIONS: Ad-alphaCaSm demonstrates a
      significant antitumor effect against pancreatic cancer both in vitro and in vivo.
      These results support the role of CaSm as a significant gene involved in the
      neoplastic transformation of pancreatic tumors. Thus CaSm represents a novel gene
      target in PC and holds potential as a new treatment approach either alone or in
      combination with existing therapies.

PMID- 10923015
TI  - Adenovirus-mediated gene therapy to liver grafts: successful gene transfer by
      donor pretreatment.
AB  - BACKGROUND: We have previously shown excellent adenoviral (Ad) gene transfection
      to transplanted liver grafts with the clamp technique (CT) where viral vector was
      delivered ex vivo and trapped in cold preserved liver grafts. In this study, we
      adopted a new gene therapy approach to achieve early transgene expression by
      donor pretreatment with viral vector and compared the efficacy of these two
      methods by using Ad vector encoding enhanced green fluorescent protein (AdEGFP)
      marker gene. METHODS: AdEGFP (1 x 10(9)plaque forming units) was delivered to the
      liver grafts by: (1) single intravenous injection to donor Lewis rats 48 hours
      before harvesting, (2) ex vivo cold infusion into the harvested liver with CT, or
      (3) a combination of both methods. Liver grafts were stored in University of
      Wisconsin solution at 4 degrees C for 18 hours and then orthotopically
      transplanted into syngeneic recipients, and the expression of EGFP was studied.
      RESULTS: With intravenous pretreatment of donor liver grafts, EGFP-expressing
      cells were detected as early as 3 hours after transplant, and moderate expression
      was seen by 12 hours. In contrast, EGFP was not detected until 12 to 24 hours
      after transplant with CT. High levels of EGFP-producing cells were seen with each
      technique at 7 days ( approximately 30% transfection efficiency). A combination
      of both methods did not enhance infectivity. Liver preservation injury was
      comparable between groups. CONCLUSIONS: Gene transfer by donor pretreatment with
      AdEGFP induces early and efficient gene transduction to liver grafts compared
      with back-table delivery with CT. This method is simple and provides early
      transgene expression in liver grafts that potentially could be used to deliver
      genes to decrease preservation injury or rejection.

PMID- 10923017
TI  - Mitral annular dynamics during rapid atrial pacing.
AB  - INTRODUCTION: Ovine mitral annular area (MAA) reduction predominantly occurs
      before ventricular systole. We used the myocardial marker methods to investigate
      left atrial and MAA dynamics during rapid atrial pacing. METHODS: Seven sheep
      underwent implantation of 21 myocardial markers around the mitral annulus, the
      left ventricle and left atrium. After 7 to 10 days, animals were studied with
      biplane videofluoroscopy to determine 3-dimensional marker coordinates unpaced
      and during rapid atrial pacing at 140 minutes(-1). Left ventricle volume, left
      atrial volume (LAV), and MAA were calculated from marker coordinates. End
      diastole (ED) was defined at peak of the electrocardiogram R wave; times of
      minimum MAA and minimum LAV were expressed relative to ED (t = 0). Percent
      reduction in MAA and LAV were calculated from maximum and minimum values between
      diastole and early systole. RESULTS: The time of minimum MAA occurred earlier
      relative to ED during rapid pacing compared with control (-48 +/- 21 vs 19 +/- 14
      msec; P <.001), as did the time of minimum LAV (-47 +/- 18 vs 4 +/- 16 msec; P
      <.001). Minimum MAA and LAV were significantly smaller with rapid pacing (6. 8 +/
      0.6 vs 6.5 +/- 0.5 cm(2); P <.05, respectively; and 15.4 +/- 2. 4 vs 16.5 +/-
      2.3 mL; P <.01, respectively), and a relatively greater fractional reduction in
      MAA and LAV was observed during presystole. CONCLUSIONS: Rapid atrial pacing
      resulted in greater MAA and LAV reduction, both of which occurred entirely during
      diastole. This study supports the notion that MAA reduction is closely linked to
      LA dynamics.

PMID- 10923018
TI  - Selective mitochondrial KATP channel opening controls human myocardial
      preconditioning: too much of a good thing?
AB  - BACKGROUND: Paradoxically, patients with noninsulin-dependent diabetes mellitus
      experience a higher cardiovascular mortality rate than patients with insulin
      dependent diabetes mellitus. We have shown that K(ATP) channel inhibition, with
      oral sulfonylureas, prevents myocardial preconditioning and may explain the
      paradox of cardiovascular death in patients with noninsulin-dependent diabetes
      mellitus. Cardiac preconditioning is an attractive protective strategy against
      any elective ischemia/reperfusion (I/R) injury. The relationship between the
      K(ATP) channels and human myocardial preconditioning has not previously been
      elucidated. METHODS: Human atrial trabeculae were harvested, placed in organ
      baths, and paced (1 Hz). Developed force was recorded during simulated 37 degrees
      C I/R (30/45 or 45/60 minutes). Before I/R, trabeculae were treated transiently
      with a selective mitochondrial K(ATP) channel opener for 5 minutes, followed by a
      10-minute washout, or were exposed to the channel opener throughout ischemia.
      Recovery of function is expressed as percentage of baseline developed force.
      Conserved creatine kinase activity (units per gram of wet tissue) was measured at
      the end of reperfusion as an indicator of cellular protection. RESULTS: Transient
      mitochondrial K(ATP) channel opening provided protection from both I/R insults.
      Surprisingly, there was no protection afforded by continuous mitochondrial K(ATP)
      channel opening. CONCLUSIONS: Transient selective mitochondrial K(ATP) channel
      opening protects both viability and function of human myocardium against I/R
      injury, although prolonged opening of the mitochondrial K(ATP) channel does not.
      These results reinforce the concept of preconditioning as a transient event that
      must be completed before the onset of ischemia.

PMID- 10923019
TI  - Supplemental dietary arginine enhances wound healing in normal but not inducible
      nitric oxide synthase knockout mice.
AB  - BACKGROUND: Although generation of nitric oxide (NO) from inducible nitric oxide
      synthase (iNOS) has been shown to be required for cutaneous wound healing, no
      differences have been noted in incisional healing between iNOS knockout (iNOS-KO)
      and wild type (WT) mice. Because supplemental dietary arginine enhances cutaneous
      healing in normal rodents and is the sole substrate for NO synthesis, we studied
      whether arginine can enhance cutaneous wound healing in iNOS-KO mice. METHODS:
      Twenty iNOS-KO and 20 WT mice, all on a C57BL/6 background, were divided into 4
      groups of 10 animals each. Ten animals with each trait were randomized to receive
      either normal food and tap water or food and water each supplemented with 0.5%
      arginine (w/w). All animals underwent a 2.5-cm dorsal skin incision with
      implantation of four 20-mg polyvinyl alcohol sponges into subcutaneous pockets.
      On postoperative day 14 the animals were killed. The dorsal wound was harvested
      for breaking strength determination and the wound sponges were assayed for
      hydroxyproline content and total wound fluid nitrite/nitrate concentration.
      RESULTS: Dietary arginine supplementation enhanced both wound breaking strength
      and collagen deposition in WT but not iNOS-KO mice. Wound fluid nitrite/nitrate
      levels were higher in WT than iNOS-KO animals but were not significantly
      influenced by additional arginine. CONCLUSIONS: These data demonstrate that
      supplemental dietary arginine enhances wound healing in normal mice. The loss of
      a functional iNOS gene abrogates the beneficial effect of arginine in wound
      healing. This suggests that the metabolism of arginine via the NO pathway is one
      mechanism by which arginine enhances wound healing.

PMID- 10923021
TI  - Establishment of a simple system to analyse the molecular interaction in the
      agglutination of Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae a-agglutinin, which is involved in mating and covalently
      anchoring to the cell wall, consists of two components, Aga1p and Aga2p, whose
      syntheses are individually regulated. To facilitate the analysis of the protein
      protein interaction on agglutination between a- and alpha-agglutinins, the
      construction of a yeast strain (MATa) with the functional protein prepared by
      genetic fusion of Aga1p- and Aga2p-encoding genes and by the expression system
      using the UPR-ICL promoter derived from the n-alkane-assimilating yeast, Candida
      tropicalis, which is functional under the condition of lower glucose
      concentration was tried and the agglutination ability of the constructed strain
      was evaluated with a yeast strain (MATa) which expressed AGalpha1 encoding alpha
      agglutinin under the control of the same promoter. The genes were integrated into
      the yeast chromosomes. Cell agglutination between both (MATa) strains was
      observed microscopically when these two strains were mix-cultured to a glucose
      decreased concentration. The agglutination was further confirmed by the
      sedimentation test and by the quantification using a filter. These results proved
      that the constructed Aga1p-Aga2p fusion protein was enoughly functional for the
      interaction with the Agalpha1 protein, and that this phenomenon occurred
      dependent on glucose concentration, but independent of the peptide pheromones
      secreted by the cells of the opposite mating types. Using this system, the role
      of two disulphide linkages between Aga1p and Aga2p on the binding activity
      between Aga2p and Aga1p was first evaluated. Under the treatment by the SH
      compound (dithiothreitol), in which Agalpha2p is easily released into the medium
      from the intact cell surface, the Aga1p and Aga2p fusion protein was a good tool
      to make clear the role of the disulphide linkages. As a result, the linkages had
      a significant effect on not only the assembly but also the binding activity. The
      novel and simple system described here may further facilitate the study of
      molecular interaction in agglutination.

PMID- 10923020
TI  - Isolation of Pichia pastoris genes involved in ER-to-Golgi transport.
AB  - Pichia pastoris has discrete transitional ER sites and coherent Golgi stacks,
      making this yeast an ideal system for studying the organization of the early
      secretory pathway. To provide molecular tools for this endeavour, we isolated P.
      pastoris homologues of the SEC12, SEC13, SEC17, SEC18 and SAR1 genes. The P.
      pastoris SEC12, SEC13, SEC17 and SEC18 genes were shown to complement the
      corresponding S. cerevisiae mutants. The SEC17 and SAR1 genes contain introns at
      the same relative positions in both P. pastoris and S. cerevisiae, whereas the
      SEC13 gene contains an intron in P. pastoris but not in S. cerevisiae. Intron
      structure is similar in the two yeasts, although the favoured 5' splice sequence
      appears to be GTAAGT in P. pastoris vs. GTATGT in S. cerevisiae. The predicted
      amino acid sequences of Sec13p, Sec17p, Sec18p and Sar1p show strong conservation
      in the two yeasts. By contrast, the predicted lumenal domain of Sec12p is much
      larger in P. pastoris, suggesting that this domain may help localize Sec12p to
      transitional ER sites. A comparison of the SEC12 loci in various budding yeasts
      indicates that the SEC12-related gene SED4 is probably unique to the
      Saccharomyces lineage.

PMID- 10923022
TI  - Mutations in the large subunit of U2AF disrupt pre-mRNA splicing, cell cycle
      progression and nuclear structure.
AB  - The prp2 gene of fission yeast has previously been shown to encode the large
      subunit of the splicing factor spU2AF. SpU2AF(59) is an evolutionarily conserved
      protein that has an arginine/serine-rich region and three RNA recognition motifs
      (RRMs). We have sequenced three temperature-sensitive alleles of prp2 and
      determined that the mutations result in single amino acid changes within one of
      the RRMs or between RRMs. All mutant alleles of prp2 have pre-mRNA splicing
      defects at the non-permissive temperature. Although the mutant strains are growth
      arrested at 37 degrees C, they do not elongate like typical fission yeast cell
      cycle mutants. The DNA of the prp2(-) strains stains more intensely than a wild
      type strain, suggesting that the chromatin may be condensed. Ultrastructural
      studies show differences in the mutant nuclei including a prominent distinction
      between the chromatin- and non-chromatin-enriched regions compared to the more
      homogenous wild-type nucleus. Two-hybrid assays indicate that some of the wild
      type protein interactions are altered in the mutant strains. These results
      suggest that normal functioning of spU2AF(59) may be essential not only for pre
      mRNA splicing but also for the maintenance of proper nuclear structure and normal
      cell cycle progression.

PMID- 10923023
TI  - Co-deletion of the MSB3 and MSB4 coding regions affects bipolar budding and
      perturbs the organization of the actin cytoskeleton.
AB  - The proteins Msb3p (Ynl293p) and Msb4p (Yol112p) of the yeast Saccharomyces
      cerevisiae are very similar in sequence and share a highly conserved domain
      called TBC. To characterize the cellular functions of these proteins, we
      constructed single and double yeast mutants by disrupting the MSB3 gene, the MSB4
      gene, or both. Co-deletion of the MSB3 and MSB4 coding regions caused growth
      inhibition in the presence of 10 mM caffeine and 4% dimethyl sulphoxide (DMSO),
      increased the sensitivity of the yeast strain to latrunculin-A, produced a random
      budding pattern in diploid cells, and affected the organization of the actin
      cytoskeleton. Caffeine sensitivity is often associated with defects in mitogen
      activated protein (MAP) kinase pathways, highly conserved mechanisms mediating
      transduction of external signals. The biological effect of DMSO in S. cerevisiae
      is unclear. The msb3 msb4 mutant's increased sensitivity to latrunculin-A
      suggests that the double mutation causes destabilization of the actin
      cytoskeleton. Microscopic observations confirmed this: in haploid and diploid
      msb3 msb4 mutant cells, polymerized actin was delocalized from the budding sites.
      Complementation studies suggested that MSB3 and MSB4 encode overlapping
      activities in the yeast cells. We thus propose that both Msb3p and Msb4p act in
      budding site selection, probably via their involvement in the organization of the
      actin cytoskeleton.

PMID- 10923024
TI  - Functional analysis of six genes from chromosomes XIV and XV of Saccharomyces
      cerevisiae reveals YOR145c as an essential gene and YNL059c/ARP5 as a strain
      dependent essential gene encoding nuclear proteins.
AB  - We report here basic functional analysis of strains deleted for six open reading
      frames (ORFs), YNL059c and YNL148c from chromosome XIV and YOR145c, YOR152c,
      YOR161c and YOR162c from chromosome XV of Saccharomyces cerevisiae. ORFs were
      replaced with the KanMX4 resistance marker using a long flanking homology PCR
      strategy in FY1679 and W303 diploid strains. Replacement cassettes were
      constructed in plasmid pUG7 and the cognate wild-type genes were recovered by gap
      repair. Sporulation and tetrad analysis revealed that deletion of YNL059c/ARP5
      was lethal for vegetative growth in strain W303 and caused severe growth defects
      in strain FY1679 while YOR145c was essential for growth in both strains. Fusion
      of the green fluorescent protein (GFP) gene to the 3' ends of the YNL059c/ARP5
      and YOR145c coding sequences created functional chimeric genes at the respective
      chromosomal loci. Both Arp5-GFP and Yor145-GFP localized to the nucleus, Yor145
      GFP concentrating in the nucleolus. The vectors containing the deletion cassettes
      and the cognate wild-type genes, the oligonucleotides, and the deletant strains
      are available from the EUROFAN resource centre EUROSCARF (Frankfurt).

PMID- 10923025
TI  - The pYC plasmids, a series of cassette-based yeast plasmid vectors providing
      means of counter-selection.
AB  - A series of 24 general-purpose yeast plasmid vectors has been constructed. The
      plasmid series is composed of inter-replaceable cassettes, allowing for easy
      interconversion of plasmid types. In addition to the usual replication origins,
      selectable markers and multiple cloning sites (MCS), cassettes dedicated to
      counter-selection have been constructed. A pair of unique 8 bp restriction enzyme
      recognition sites flank each type of cassette, FseI in the case of yeast
      replication origins, AscI in the case of selectable markers, PacI in the case of
      counter-selectable markers and NotI in the case of the MCS. Thus, any given
      cassette can be replaced by another cassette of the same type, facilitating
      interconversion of any given plasmid from one type to another, even after the
      insertion of DNA into the MCS. Hence, the plasmids have been named pYC for 'yeast
      cassettes'. The cassettes consist of either NONE, CEN4/ARS or 2micro as
      replication origin, either URA3, MET2-CA (Lg-MET2) or the G418 resistance gene
      (the apt1 gene from bacterial transposon Tn903, encoding aminoglycoside
      phosphotransferase) as selectable markers, either NONE, PMET25-PKA3 or PCHA1-PKA3
      as counter-selectable marker, and the MCS, containing recognition sites for
      AflII, AvrII, BspEI, PmeI, SacII, SalI, SunI, BamHI, EcoRI, HindIII, KpnI, MluI,
      NarI and SacI (of which the seven first are unique in all plasmids). The counter
      selectable markers consist of the PKA3 gene under control of the conditional
      MET25 or CHA1 promoters. At activating conditions these promoters express the
      PKA3 gene at toxic levels, facilitating easy selection for loss of plasmid or
      'loop-out' of plasmid DNA sequence after genomic integration.

PMID- 10923026
TI  - Identification of a Candida albicans homologue of the PHO85 gene, a negative
      regulator of the PHO system in Saccharomyces cerevisiae.
AB  - In a screen for the protein kinase genes of the human pathogenic yeast Candida
      albicans, a putative homologue (CaPHO85) of PHO85, a negative regulator of the
      PHO system of Saccharomyces cerevisiae, which is one of the cyclin-dependent
      protein kinases (CDKs), was isolated. An open reading frame (ORF) of this gene
      was identified encoding a predicted protein of 326 amino acids with a calculated
      molecular weight of 37.6 kDa. The amino acid sequence is highly homologous to S.
      cerevisiae Pho85 (62% identity) and its Aspergillus nidulans homologue (70%
      identity), but less homologous to Cdc28 (50% identity) of S. cerevisiae and to
      its C. albicans homologue CaCdc28 (49% identity), both of which are also CDK. The
      coding region for the C. albicans gene was interrupted by an intron of 81
      nucleotides near the sequence encoding the N-terminal region, similarly to the
      case of the S. cerevisiae PHO85 gene. Alignment of CaPho85 with various yeast
      CDKs revealed that most of the domains for ATP-binding and protein kinase
      activity are conserved among fungal species. Southern blot analysis indicated
      that CaPHO85 is most likely present as a single copy gene. This gene complemented
      the pho85 mutation of S. cerevisiae by transformation.

PMID- 10923029
TI  - Current awareness on yeast.
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 yeasts. Each bibliography is divided into 10
      sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4
      Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9
      Medical Mycology; 10 Recombinant DNA Technology. 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. (5 weeks journals - search completed 31st May 2000)

PMID- 10923028
TI  - The mating-type region of Schizosaccharomyces pombe h(-S) 972: sequencing and
      analysis of 69 kb including the expressed mat1 locus.
AB  - The sequence has been determined of 68 897 bp of genomic DNA including the
      expressed mat1 mating-type locus from Schizosaccharomyces pombe h(-S) strain 972.
      The DNA sequence, located on the long arm of fission yeast chromosome II and
      contained in two cosmid clones, was analysed to reveal one autonomously
      replicating sequence, two retrotransposon long terminal repeats (LTRs), one
      tRNA(Gly) gene and 33 open reading frames (ORFs), of which 15 contain introns.
      Nine of these ORFs code for previously described genes (trt1, rpl10, rps21, nif1,
      sui1 (psu1), matMi, matMc, let1 and rpa4), one of which (trt1) contains 15
      introns, the highest number yet recorded in a gene of S. pombe. Of the remaining
      24 ORFs, sequence similarity suggests that the function of 13 of the encoded
      proteins may be predicted and these include four mitochondrial proteins, two
      transport proteins, two signalling molecules, a component of serine
      palmitolytransferase, a homologue of 3-methyladenine DNA glycosylase, a
      multifunctional alcohol dehydrogenase, a killer toxin sensitivity factor and an
      acetyl transferase. Six deduced sequences appear to be related to proteins of
      unknown function in Saccharomyces cerevisiae or S. pombe and the remaining five
      are hypothetical proteins.

PMID- 10923027
TI  - Identification of YPD1, a gene of Candida albicans which encodes a two-component
      phosphohistidine intermediate protein.
AB  - We have identified the YPD1 phosphohistidine intermediate two-component gene of
      Candida albicans. YPD1 has an open reading frame of 552 bp. It is located on
      chromosome 1 and an mRNA specific for YPD1 is detected under both yeast and
      hyphal growth. YPD1 encodes a protein of 184 amino acids with an estimated
      molecular mass of 20.5 kDa. A search for similarities with other proteins in
      databases showed that CaYpd1p exhibits the greatest overall similarity with Ypd1p
      from Saccharomyces cerevisiae (34.2% identity; 49.4% similarity) as well as with
      the C-terminus half of a protein from Schizosaccharomyces pombe (Accession No.
      CAA22174). However, CaYpd1p also shows similarity with other eukaryotic and
      prokaryotic proteins which function as phosphohistidine intermediates in two
      component phospho-relay systems. In these cases, similarity was restricted to the
      amino acid sequences which surround the conserved histidine residue that is
      phosphorylated. In addition, CaYPD1 (but not CaYPD1(H69Q)) complements the lack
      of YPD1 in S. cerevisiae. This observation supports the premise that CaYpd1p also
      may function as a phosphohistidine intermediate protein in C. albicans.

PMID- 10923030
TI  - VARIATION, DATABASES, and DISEASE: new directions for human mutation

PMID- 10923031
TI  - Mutations in holoprosencephaly.
AB  - Holoprosencephaly (HPE) is the most common developmental defect of the forebrain
      and midface in humans. In holoprosencephaly the cerebral hemispheres of the brain
      fail to separate into distinct left and right hemispheres. This malformation is
      due to the improper specification and formation of the forebrain during early
      development. When one considers the great number and kinds of genetic
      interactions that must occur to properly pattern the developing forebrain, it is
      not surprising that HPE is extremely heterogeneous. In addition to teratogenic
      agents, several genes are implicated as the cause of HPE. At least 12 different
      loci have been associated with HPE and now several distinct human genes for
      holoprosencephaly have been identified. These genes include Sonic Hedgehog (SHH),
      ZIC2, SIX3, and TG-interacting factor (TGIF). Here we present an overview of the
      presently known genes causing human holoprosencephaly. We discuss their
      functional role in development of the forebrain and summarize the mutations and
      polymorphisms that have been identified within them. Hum Mutat 16:99-108, 2000.
      Published 2000 Wiley-Liss, Inc.

PMID- 10923032
TI  - Mutations of the human PTEN gene.
AB  - PTEN (phosphatase and tensin homolog deleted on chromosome ten), a recently
      discovered tumor suppressor gene, appears to negatively control the
      phosphoinositide 3-kinase signaling pathway for regulation of cell proliferation
      and cell survival by dephosphorylating the phosphatidylinositol 3,4,5
      triphosphate. To date, 110 germline PTEN mutations have been reported in patients
      affected with two tumor predisposing syndromes, each having overlapping clinical
      features: Cowden disease and Bannayan-Riley-Ruvalcaba syndrome. These germline
      mutations are scattered along the length of the gene, with the exception of exon
      9 (no mutation reported) and exon 1 (only two mutations reported). A mutational
      hot spot is found in exon 5, which encodes the phosphatase catalytic core motif,
      and recurrent mutations are also found at CpG dinucleotides suggesting
      deamination-induced mutations. PTEN has also been found to be defective in a
      large number of sporadic human tumors. In this article, 332 somatic point
      mutations of PTEN, occurring in primary tumors or metastasis, have been reviewed.
      Somatic PTEN mutations are more particularly involved in two types of human
      cancers: endometrial carcinomas and glioblastomas. In most cases, these somatic
      mutations result in protein inactivation and, as with germline mutations,
      recurrent somatic mutations are found in CpG dinucleotides. A mutagenesis by
      insertion-deletion in repetitive elements is however specifically observed in
      endometrial carcinomas.

PMID- 10923034
TI  - The thermolabile variant 677C-->T can further reduce activity when expressed in
      cis with severe mutations for human methylenetetrahydrofolate reductase.
AB  - Methylenetetrahydrofolate reductase (MTHFR) catalyses the reduction of 5,10
      methylenetetrahydrofolate to 5-methyltetrahydrofolate, a carbon donor for
      homocysteine remethylation to methionine. Severe MTHFR deficiency is associated
      with hyperhomocysteinemia and homocystinuria. These patients show a wide variety
      of neurological and vascular symptoms, with variable age of onset. Residual
      enzyme activity is usually less than 20% of control values, and correlates
      reasonably well with age of onset of symptoms. A milder deficiency of MTHFR, with
      30%-50% residual enzyme activity and increased enzyme thermolability, has been
      described as a risk factor for vascular disease and for neural tube defects. In
      earlier work, we isolated the human cDNA for MTHFR, and reported 14 mutations in
      severe MTHFR deficiency, as well as a common 677C-->T missense mutation (Ala-
      >Val) that encodes the thermolabile MTHFR. This variant has also been observed in
      some patients with severe MTHFR deficiency, in cis with their severe mutations.
      We report here the in vitro expression of seven severe MTHFR mutations in a
      bacterial expression system; six of these were expressed in cis with the Val
      allele to mimic the situation in the patients. We show that three of these
      constructs have significantly reduced enzyme activity (<10% of control); the
      presence of the thermolabile variant in these patients in cis is unlikely to
      affect enzyme function since activity is already low. One mutation causes a
      dramatic increase in activity when it is expressed in cis with the Ala allele,
      but is associated with extreme lability when in cis with the Val allele. Three
      mutations cause moderate decreases in enzyme activity, with a further decrease in
      activity when they are in cis with the Val allele. We hypothesize that
      deleterious mutations which alter stability may be compromised to a greater
      degree when the thermolabile variant is present on the same allele.

PMID- 10923033
TI  - The breast cancer information core: database design, structure, and scope.
AB  - The Breast Cancer Information Core (BIC) is an open access, on-line mutation
      database for breast cancer susceptibility genes. In addition to creating a
      catalogue of all mutations and polymorphisms in breast cancer susceptibility
      genes, a principle aim of the BIC is to facilitate the detection and
      characterization of these genes by providing technical support in the form of
      mutation detection protocols, primer sequences, and reagent access. Additional
      information at the site includes a literature review compiled from published
      studies, links to other internet-based, breast cancer information and research
      resources, and an interactive discussion forum which enables investigators to
      post or respond to questions and/or comments on a bulletin board. Hum Mutat
      16:123-131, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10923035
TI  - Study of the voltage-gated sodium channel beta 1 subunit gene (SCN1B) in the
      benign familial infantile convulsions syndrome (BFIC).
AB  - Benign familial infantile convulsions (BFIC) is a rare autosomal dominant
      epilepsy syndrome. This syndrome has been recently described in Italian and
      French pedigrees. Patients present with partial, then generalized seizures, with
      onset at age three months. The seizures usually spontaneously cease after one
      year without treatment, leaving no neurological abnormalities. We have mapped
      BFIC to chromosome 19q in five Italian pedigrees. The sodium channel beta1
      subunit gene (SCN1B) maps to this candidate region and has been shown to be
      involved in one Australian pedigree with generalized epilepsy and febrile
      seizures "plus" (GEFS +). In this family, a missense mutation in SCN1B
      cosegregates with the GEFS+ phenotype. BFIC and GEFS+ have clinical features in
      common, therefore SCN1B is a candidate gene for BFIC. We studied SCN1B exons 1,
      2, 3, 4, and 5, using four SSCP methods in 10 Caucasian BFIC probands of Western
      Europe. We found no exon variants. One variant was identified in intron 5 (IVS5
      10C>G), which did not segregate with BFIC and was observed in 9.2% controls. A
      second variant in intron 5 was identified (IVS5+30G>A). It was rare, as not
      observed in controls, but not segregating with the BFIC phenotype.

PMID- 10923037
TI  - OCRL1 mutation analysis in French Lowe syndrome patients: implications for
      molecular diagnosis strategy and genetic counseling.
AB  - The oculocerebrorenal syndrome of Lowe (OCRL) is a rare X-linked recessively
      inherited disease characterized by a severe pleiotropic phenotype including
      mental retardation, bilateral congenital cataract, and renal Fanconi syndrome.
      The gene responsible for OCRL encodes an inositol polyphosphate-5-phosphatase. We
      performed mutation analysis in 36 families and characterized 27 new mutations
      with two of them being recurrent mutations. The panel of mutations consisted of
      27 truncating mutations (frameshift, nonsense, splice site mutations, and large
      genomic deletions), one in-frame deletion, and six missense mutations. The four
      large genomic deletions occurred in the first half of the gene, whereas all the
      remaining mutations took place in the second part of the gene and were
      concentrated in a few exons. This distribution may be of interest in terms of
      screening strategy when looking for unknown mutations. Haplotyping of the
      families was performed to analyze segregation of the mutated loci, and revealed a
      somatic mosaicism in one family. This is the second case of mosaicism we
      characterized in a total panel of 44 unrelated families affected by Lowe's
      syndrome. Considering the low number of families investigated, it appeared that
      somatic and germinal mosaicisms are quite common in this disease and must be
      taken into account for genetic counseling.

PMID- 10923036
TI  - Spectrum of CFTR mutations in cystic fibrosis and in congenital absence of the
      vas deferens in France.
AB  - We have collated the results of cystic fibrosis (CF) mutation analysis conducted
      in 19 laboratories in France. We have analyzed 7, 420 CF alleles, demonstrating a
      total of 310 different mutations including 24 not reported previously, accounting
      for 93.56% of CF genes. The most common were F508del (67.18%; range 61-80), G542X
      (2.86%; range 1-6.7%), N1303K (2.10%; range 0.75-4.6%), and 1717-1G>A (1.31%;
      range 0-2.8%). Only 11 mutations had relative frequencies >0. 4%, 140 mutations
      were found on a small number of CF alleles (from 29 to two), and 154 were unique.
      These data show a clear geographical and/or ethnic variation in the distribution
      of the most common CF mutations. This spectrum of CF mutations, the largest ever
      reported in one country, has generated 481 different genotypes. We also
      investigated a cohort of 800 French men with congenital bilateral absence of the
      vas deferens (CBAVD) and identified a total of 137 different CFTR mutations.
      Screening for the most common CF defects in addition to assessment for IVS8-5T
      allowed us to detect two mutations in 47.63% and one in 24.63% of CBAVD patients.
      In a subset of 327 CBAVD men who were more extensively investigated through the
      scanning of coding/flanking sequences, 516 of 654 (78. 90%) alleles were
      identified, with 15.90% and 70.95% of patients carrying one or two mutations,
      respectively, and only 13.15% without any detectable CFTR abnormality. The
      distribution of genotypes, classified according to the expected effect of their
      mutations on CFTR protein, clearly differed between both populations. CF patients
      had two severe mutations (87.77%) or one severe and one mild/variable mutation
      (11.33%), whereas CBAVD men had either a severe and a mild/variable (87.89%) or
      two mild/variable (11.57%) mutations.

PMID- 10923038
TI  - Screening the 3' region of the polycystic kidney disease 1 (PKD1) gene in 41
      Bulgarian and Australian kindreds reveals a prevalence of protein truncating
      mutations.
AB  - Screening for disease-causing mutations in the unique region of the polycystic
      kidney disease 1 (PKD1) gene was performed in 41 unrelated individuals with
      autosomal dominant polycystic kidney disease. Exons 34-41 and 43-46 were assayed
      using PCR amplification and SSCP analysis followed by direct sequencing of
      amplicons presenting variant SSCP patterns. We have identified seven disease
      causing mutations of which five are novel [c.10634-10656del; c.11587delG; IVS37
      10C>A; c.11669-11674del; c.13069-13070ins39] and two have been reported
      previously [Q4010X; Q4041X]. Defects in this part of the gene thus account for
      17% of our group of patients. Five of the seven sequence alterations detected are
      protein-truncating which is in agreement with mutation screening data for this
      part of the gene by other groups. The two other mutations are in-frame deletions
      or insertions which could destroy important functional properties of polycystin
      1. These findings suggest that the first step toward cyst formation in PKD1
      patients is the loss of one functional copy of polycystin 1, which indirectly
      supports the "two-hit" model of cystogenesis where a second somatic mutation
      inactivating the normal allele is necessary to occur for development of the
      disease condition.

PMID- 10923039
TI  - Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1)
      in russian charcot-marie-tooth neuropathy patients; irina V. Mersiyanova,
      sookhrat M. Ismailov, alexandr V. Polyakov, elena L. Dadali, valeriy P. Fedotov,
      eva nelis, ann Lofgren, vincent timmerman, christine van broeckhoven, and oleg V.
      Evgrafov (Article was originally published in human mutation 15:340-347, 2000)
AB  - The authors wish to correct a mistake which occurred in the reporting of one of
      the mutations. The mutation in Cx32 Met34Lys is wrongly described as 100A>G. The
      correct description of the mutation should be 101T>A (Met34Lys).

PMID- 10923040
TI  - Screening of the PKD1 duplicated region reveals multiple single nucleotide
      polymorphisms and a de novo mutation in Hellenic polycystic kidney disease
      families.
AB  - Mutations in the PKD1 gene account for approximately 85% of cases with autosomal
      dominant polycystic kidney disease (ADPKD1; MIM# 601313), which is considered one
      of the most frequent monogenic disorders, with a frequency of approximately
      1:1000. The main symptom is the formation of fluid-filled cysts in the kidneys
      and less often in other organs, such as the liver and pancreas. Since the cloning
      of the gene many mutations have been identified, although the screening is
      hampered by several unique features of this gene, the most significant one being
      that approximately 70% of the sequence at the 5'-end, is reiterated elsewhere on
      chromosome 16 with homology approaching 95%. Here, we used an oligonucleotide
      primer anchored in the unique part in exon 34, paired with a forward primer in
      exon 23 for specifically amplifying PKD1 sequences. We screened for mutations in
      samples from 32 Hellenic ADPKD families. We detected seven sequence variants,
      five of which most probably are single nucleotide polymorphisms (SNPs),
      especially useful for linkage analysis and disease association studies. One is a
      missense change, segregating with ADPKD in one family. The last one is a missense
      non-conservative change, H2921P, which appeared de novo in the proband,
      concurrently with the disease phenotype, and was passed on to another two
      generations. Two siblings who inherited the same haplotype as the proband, but
      not the de novo mutation, were not affected. This is only the fourth case of a
      molecularly documented de novo mutation in ADPKD. Somatic mosaicism in peripheral
      blood leukocytes of the proband was tested and excluded. Hum Mutat 16:176, 2000.

PMID- 10923041
TI  - Characterization of 11 new mutations in COL3A1 of individuals with Ehlers-Danlos
      syndrome type IV: preliminary comparison of RNase cleavage, EMC and DHPLC assays.
AB  - We report on 12 patients with EDS IV in whom clinical diagnosis was confirmed by
      biochemical analysis of collagen type III, and further proven by mutation
      analysis of the COL3A1 gene. Four overlapping RT-PCR products covering the coding
      sequence for the triple-helical domain of type III collagen were analyzed by
      direct sequencing. So far, we have identified, 4 base changes at donor splice
      junctions, and 1 base change at an acceptor splice site, which all affect mRNA
      splicing; 1 genomic deletion, which removes exon 45; and 6 nucleotide changes,
      which cause substitutions of glycine residues within the triple helix. Eleven of
      the 12 identified mutations are newly recognized. Furthermore, we report a
      preliminary comparison of RNase cleavage, EMC and DHPLC assays in mutation
      detection in the COL3A1 gene.

PMID- 10923042
TI  - Molecular analysis in glycogen storage disease 1 non-A: DHPLC detection of the
      highly prevalent exon 8 mutations of the G6PT1 gene in German patients.
AB  - We investigated the molecular basis of glycogen storage disease type 1 non-A
      (GSD1 non-A) in 21patients. In addition to 8 novel mutations within the G6PT1
      gene (c.250T>A, c.580G>A, c.627C>T, c.653-4delAG, c. 844C>A, c.1071A>C,
      c.1268G>A, c.1348G>A), we found a remarkably high prevalence of exon 8 mutations
      in German patients. The c.1211-2delCT mutation and the c.1184G>T mutation
      accounted for 32% and 29% of mutant chromosomes, respectively, supporting the
      hypothesis of a Middle European origin of these two mutations. Together with less
      common mutations, 79% of German GSD1 non-A patients were either homozygous or
      heterozygous for an exon 8 mutation. In addition to direct sequencing, these
      exon8 mutations could be detected by mutation-specific methods such as the
      detection of heteroduplex formation on polyacrylamide gel electrophoresis or by
      the amplification of DNA segments by allele-specific oligonucleotides.
      Furthermore, the use of denaturating high performance liquid chromatography
      (DHPLC) allowed a 100% detection and discrimination of all exon 8 mutations. In
      conclusion from these results, we recommend the use of either conventional or
      DHPLC screening as the initial non-invasive and efficient diagnostic procedure in
      patients with GSD1 non-A from populations with a similar distribution of
      mutations. Hum Mutat 16:177, 2000.

PMID- 10923043
TI  - Mutations in the peripheral myelin protein zero and connexin32 genes detected by
      non-isotopic RNase cleavage assay and their phenotypes in Japanese patients with
      Charcot-Marie-Tooth disease.
AB  - Mutations of myelin protein zero (MPZ) and connexin32 (Cx32) genes were examined
      in 70 unrelated Japanese patients with Charcot-Marie-Tooth disease (CMT) without
      PMP22 gene duplication. A new method, which could detect base pair mismatches
      with Rnase cleavage on agarose gel electrophoresis, identified 5 and 4 mutations
      of the MPZ and Cx32 genes, respectively, including one novel mutation (Ser128Ter)
      of Cx32. This non-isotopic RNase cleavage assay (NIRCA) employed in the present
      study is very suitable for exploring mutations of MPZ and Cx32 genes in a large
      number of CMT patients, as the phenotype of patients with CMT is greatly
      divergent from demyelinating to axonal pathology.

PMID- 10923045
TI  - Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in
      a human case with heme oxygenase-1 deficiency.
AB  - We previously reported a family affected by heme oxygenase-1 (HO-1) deficiency
      [Yachie et al., 1999]. The proband was a compound heterozygote for a complete
      loss of exon 2 (the maternal allele) and a two-nucleotide deletion within exon 3
      (the paternal allele). In this report, we describe a large genomic deletion (1730
      bp) including entire exon 2 in this family as a specific mechanism generating
      exon-2 absence observed in the HO-1 mRNA. Analysis of the deletion junction
      demonstrated fusion of a 5' portion of Alu-Sx element with a 3' portion of Alu-Sq
      element. The junction contained sequences with high homology to the
      recombinogenic Alu "core" sequence. These structural features of the HO-1 gene
      suggest homologous recombination associated with Alu element. This study presents
      the initial characterization of the HO-1 gene defect causing a human case of HO-1
      deficiency and provides the molecular basis for understanding this genetic
      disease.

PMID- 10923044
TI  - Eleven novel APC mutations identified in Portuguese FAP families.
AB  - Germline mutations of the adenomatous polyposis coli (APC) gene are responsible
      for familial adenomatous polyposis (FAP), an autosomal dominant predisposition to
      colorectal cancer. In the present study we screened all of the exons of the APC
      gene in individuals belonging to 85 Portuguese FAP families. We here report
      eleven novel mutations which are predominantly frameshifts or single base
      substitutions, resulting in premature stop codons. Hum Mutat 16:178, 2000.

PMID- 10923046
TI  - mut0 methylmalonic acidemia: eleven novel mutations of the methylmalonyl CoA
      mutase including a deletion-insertion mutation.
AB  - Methylmalonic aciduria (MMA) is an autosomal-recessive disorder caused by
      inadequate function of methylmalonyl-CoA mutase (MCM), a nuclear-encoded,
      mitochondrial enzyme that uses adenosylcobalamin as a cofactor. Biochemical cell
      studies have delineated phenotypic variants: mut(0) phenotypes in which there is
      no detectable enzymatic activity and mut- phenotypes in which there is residual
      cobalamin-dependent activity. Mutation screening in MMA has led to the detection
      of 30 disease-specific mutations. In 14 patients with the mut(0) phenotype we
      found 11 novel mutations (K54X, A137V, F174S, 620insA, G203R, Q218H, A535P,
      H627R, 2085delG and 2270del4/ins5), 6 of them homozygous, consisting of 1
      nonsense, 6 missense, 1 splice site, and 3 frame shift mutations. The position in
      relation to different functional domains in MCM allow for an interpretation of
      the identified mutations. Hum Mutat 16:179, 2000.

PMID- 10923047
TI  - A new polymorphism, g119A>G, in the integrin alpha 7 (ITGA7) gene.

PMID- 10923048
TI  - Transthyretin Ala97Ser is associated with familial amyloidotic polyneuropathy in
      a Chinese-Taiwanese family.

PMID- 10923049
TI  - A novel variant of human lysozyme (T70N) is common in the normal population.

PMID- 10923050
TI  - A novel mutation in the beta-hexosaminidase beta-subunit gene in a 14-month-old
      Korean boy with Sandhoff disease: first reported Korean case.

PMID- 10923051
TI  - Two novel germline mutations (Y548X and K732X) of the MLH1 gene in Czech patients
      with hereditary nonpolyposis colorectal cancer.

PMID- 10923052
TI  - Common polymorphism in p53 intron 2, IVS2+38G>C.

PMID- 10923053
TI  - Anosognosia and Alzheimer's disease: the role of depressive symptoms in mediating
      impaired insight.
AB  - The relation between anosognosia and dementia severity in Alzheimer's disease
      (AD) has been unclear. We constructed a measure that quantified the difference
      between the perceptions of deficits of patients with AD (n = 23) and ratings from
      a knowledgeable informant as a measure of anosognosia. There was no correlation
      between dementia severity and anosognosia. However, dementia severity was
      positively correlated with the degree of anosognosia after controlling for
      depressive symptomatology (p =.03). Post-hoc analyses, also controlling for
      depressive symptoms, indicated that higher levels of anosognosia were associated
      with lower performance on specific cognitive tasks. These results suggest
      depressive symptoms may confound the relationship between anosognosia and
      dementia severity.

PMID- 10923054
TI  - Dementia rating scale performance: a comparison of vascular and Alzheimer's
      dementia.
AB  - Differences in the pattern of neuropsychological dysfunction associated with
      Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the
      Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients
      with AD; (2) patients with single stroke (CVA); and (3) patients with multiple
      cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on
      patients that met the DRS criteria for dementia. Dementia groups were similar in
      age, education, and severity of dementia. Comparisons of the AD and two VaD
      groups across the specific DRS-scales (Attention, Conceptualization,
      Construction, Initiation/Perseveration, and Memory) indicated that patients with
      AD were more impaired on the DRS-Memory while the patients with VaD were more
      impaired on the DRS-Construction. Additionally, patients with VaD related to MI
      scored lower on the DRS-Initiation/Perseveration as compared to patients with AD,
      and patients with AD scored lower on the DRS-Conceptualization as compared to
      patients with VaD related to CVA. These results are indicative of qualitative
      differences in the pattern of cognitive deficits associated with the two types of
      dementia.

PMID- 10923055
TI  - Source memory and encoding strategy in normal aging.
AB  - Of the memory deficits associated with aging, elders are most impaired at
      attributing the source to remembered information. Additionally, aging is marked
      by a decrease in the use of encoding strategies that are thought to enhance the
      acquisition and retention of information. We examined how manipulating the
      encoding strategy during acquisition affected item and source memory in 32 young
      and 68 elderly participants. Elderly participants were dichotomized into young
      old and old-old based upon the median age (74 years). Memory was assessed using
      Word List A from the California Verbal Learning Test (CVLT) and its alternate
      form. Encoding strategy was manipulated by semantic clustering. For the Blocked
      List, words were presented grouped into their semantic categories, whereas for
      the Unblocked List categories were intermixed within the list. Item and source
      memory judgments were made 20 minutes after the final CVLT recall trial and again
      one week later. Results revealed a disproportionate decline in source, compared
      to item memory in the two older groups. Semantic blocking enhanced item memory
      for the elders, but not for the young. The amount of semantic clustering
      performed by the elders showed a decline with age and was positively related to
      source performance. Results also suggest that subtle age-related changes in
      semantic knowledge may be related to declines in semantic clustering and memory
      performance.

PMID- 10923056
TI  - Stroop interference in Chinese and English.
AB  - This study examined whether Chinese and English orthographies would bring about a
      different Stroop effect. Eighty-five right-handed participants belonging to
      Chinese-English bilingual and English monolingual groups were invited to
      participate. The Stroop Color-Word Test - Victoria version (VST) and the Chinese
      version of the VST (CST) were the outcome measures. The bilinguals completed both
      the VST and CST, whereas the monolinguals performed only the VST. The results in
      both between- and within-group comparisons revealed no significant difference in
      Stroop effect no matter whether Chinese or English orthographies were used. This
      does not support the orthographic variation hypothesis and suggests that Chinese
      orthography does not generate a greater Stroop effect than English orthography.

PMID- 10923057
TI  - Use of advance information in patients with schizophrenia.
AB  - To document possible motor disturbance in schizophrenia, we examined the ability
      to use advance information (or cues) to plan movements in a sequential button
      pressing task in 12 Clozapine medicated patients. Programming of movements under
      various cues revealed that patients with schizophrenia, relative to controls,
      initiated movements slower to the right than left, providing possible evidence
      for right hemineglect (left hemisphere dysfunction). Additionally, patients with
      schizophrenia had difficulty in the initiation of movements in the absence of a
      cue, suggesting internal cue generation difficulty for movement related to some
      form of fronto-striatal disturbance. Motor abnormalities were predominantly
      observed at the level of movement initiation, but not execution, contrary to
      basal ganglia disorders such as Parkinson's and Huntington's disease.

PMID- 10923058
TI  - Cognitive decline in patients with familial Alzheimer's disease associated with
      E280a presenilin-1 mutation: a longitudinal study.
AB  - Few longitudinal studies have been carried out to investigate the cognitive
      decline in early onset of familial Alzheimer's disease (FAD). In this study 12
      patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic
      Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal
      controls (M age = 45.01, SD = 7.24) were selected. A comprehensive
      neuropsychological battery was administered three times over a period of 18
      months. Individuals designated as FAD met the criteria for dementia and were
      positive for the E280A presenilin 1 mutation. Participants with SAD met the
      criteria for dementia and were negative for the E280A presenilin 1 mutation.
      Normal control participants were the FAD patients' relatives, who were negative
      for the mutation. Two groups of neuropsychological instruments were administered:
      (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD)
      neuropsychological test battery, and (2) additional neuropsychological tests of
      abstraction and constructional abilities. Patients with FAD were significantly
      impaired on all measures at the first examination except for reading of words.
      While the performance of the normal controls remained unchanged over the 18
      months for most neuropsychological tests, the patients with FAD displayed a
      decline in verbal memory, language, constructional and abstraction tests. The
      greatest decline was observed on the Mini-Mental State Exam scores. Patients with
      SAD demonstrated a similar pattern of cognitive decline, but the decline was
      faster in FAD than in SAD participants.

PMID- 10923059
TI  - Exacting assessments: do older adults fatigue more quickly?
AB  - To determine whether neuropsychological testing is fatiguing, and whether it is
      more fatiguing to older than younger adults, 351 healthy, community living
      adults, between 18 and 91 years of age, completed a 3 to 4 hour battery of tests
      focusing on sensation, perception, attention, memory and knowledge. The battery
      included 3 critical tests: one for assessing the speed of making simple reactions
      and two for assessing the speed of making decisions. For half of the
      participants, the critical tests were administered only once, at the end of the
      session; for the remaining participants, the critical tests were given at the
      beginning and end of the session. The results show no evidence of fatigue effects
      with participants from any age group. In view of the type and variety of
      instruments in our battery, we believe our results will generalize to a wide
      range of testing situations. The participants in our study were healthy adult
      volunteers, however, and thus we recommend caution in generalizing the results to
      clinical populations.

PMID- 10923060
TI  - Progressive decline in NART score with increasing dementia severity.
AB  - Although the National Adult Reading Test (NART) is widely used to estimate
      premorbid intellectual ability in adults with possible or probable dementia, it
      may be less resilient to the progress of Alzheimer's Disease (AD) than was
      initially assumed. This paper reports performance at four annual assessments of
      78 people with either autopsy confirmed (n = 50) or clinical diagnosis of AD (n =
      28). Results indicate that NART score does decline over time and that extent of
      decline is a function of MMSE score on entry to the study but is not dependent on
      age, education or time post onset of dementia.

PMID- 10923061
TI  - Trail making test, part B as a measure of executive control: validation using a
      set-switching paradigm.
AB  - Recent controversy surrounds the use of the Trail Making Test as a measure of
      cognitive flexibility, given that the Trail Making Test, Part B (TMT-B) also
      differs from Part A (TMT-A) in factors of motor control and perceptual
      complexity. The present study compared performance in the TMT and a set-switching
      task in order to test the assumption that cognitive flexibility is captured in
      TMT-B performance. Set-switching tasks have low motor and perceptual selection
      demands, and therefore provide a clearer index of executive function. In this
      study, participants made category judgments for digits, letters, or symbols
      across a series of trials, and performance for consecutive same-task trials was
      compared with task-switch trials. Results of the set-switching task indicated
      significant switch cost, but only for the situation of task alternation (e.g., an
      ABA series), suggesting that task-set inhibition may play a role in this effect.
      Alternating-switch cost was significantly correlated with TMT-B performance,
      especially with the TMT-B to TMT-A ratio (B/A). Cost for alternating switches was
      especially large for participants with B/A ratio > 3. These results provide
      direct evidence that the B/A ratio of performance in the TMT provides an index of
      executive function.

PMID- 10923062
TI  - Are trail making and color trails tests of equivalent constructs?
AB  - The Color Trails Test (CTT) was developed as a culturally fair analogue of the
      Trail Making Test (TMT). This study examined the equivalence of these two tests
      for Chinese individuals in Hong Kong. One hundred and eight Chinese people
      volunteered for this study, and were classified into four groups according to
      their age and level of education. Their performance on these two tests was
      compared. The findings suggested that age and level of education indeed played
      significant roles in their performance on these two tests. Strong correlations (r
      = 0.72) were only observed between scores on Part B of the TMT and Part 2 of the
      CTT when the participants were older and had higher levels of education. This
      suggests that the equivalent construct of the Trail Making and Color Trails Tests
      can only be examined and established within specific age and education
      parameters.

PMID- 10923063
TI  - Epithelioid hemangioendothelioma, multiple focal nodular hyperplasias, and
      cavernous hemangiomas of the liver.

PMID- 10923064
TI  - Connectivity. The millennium challenge for point-of-care testing.

PMID- 10923066
TI  - Follow-up of abnormal gynecologic cytology. A College of American Pathologists Q
      Probes Study of 16,312 cases from 306 laboratories.

PMID- 10923065
TI  - Surgical pathologic findings of extratemporal-based intractable epilepsy. A study
      of 133 consecutive cases.

PMID- 10923067
TI  - A portrait in history. The legacy of Reinier de Graaf.

PMID- 10923069
TI  - Policies and procedures related to weak D phenotype testing and Rh immune
      globulin administration. Results from supplementary questions to the
      Comprehensive Transfusion Medicine Survey of the College of American
      Pathologists.
AB  - OBJECTIVE: To determine and evaluate policies and procedures related to weak D
      phenotype testing and terminology and the administration of Rh immune globulin in
      selected clinical situations. Design, Setting, and Participants.-Institutions
      participating in the College of American Pathologists 1999 J-A Comprehensive
      Transfusion Medicine Survey program were asked to respond to a series of
      supplementary questions related to weak D phenotype testing and Rh immune
      globulin administration. More than 3500 institutions and transfusion services
      participated. RESULTS: Most supplementary questions elicited more than 3000
      responses. Despite no clinical or regulatory mandate, 58. 2% of transfusion
      services routinely perform an antiglobulin test for the weak D phenotype in
      patients who test negative with anti-D reagents. Significant differences were
      found concerning the transfusion of blood components to patients with the weak D
      phenotype and the administration of Rh immune globulin to these individuals. At
      least one patient with the weak D phenotype with anti-D alloantibody formation
      was observed during a 12-month period by 31.8% of transfusion services.
      CONCLUSIONS: Significant variability concerning policies and procedures related
      to weak D typing and terminology was found in this survey. Transfusion of blood
      components to patients with the weak D phenotype and the administration of Rh
      immune globulin also demonstrated variations. Anti-D alloantibody formation by
      patients with the weak D phenotype may not be as rare as previously thought.
      Additional study related to the clinical significance of these results is
      warranted.

PMID- 10923070
TI  - Quality control of test systems waived by the Clinical Laboratory Improvement
      Amendments of 1988. Perceptions and practices.
AB  - CONTEXT: Recent advances in laboratory testing technology have resulted in a
      rapidly increasing number of test systems targeted for physician office, point-of
      care, and home health care settings. With enhanced error detection mechanisms and
      unitized reagents, these new systems simplify the testing process and the
      assessment of analytical test performance. Many also meet the criteria set by the
      Clinical Laboratory Improvement Amendments of 1988 (CLIA) to qualify as waived
      test systems, and laboratories using only waived tests are subject to very
      limited regulatory oversight. OBJECTIVE: To evaluate use patterns and perceptions
      about quality control requirements with respect to waived testing. DESIGN AND
      SETTING: Survey of a network of 431 hospital, independent, and physician office
      laboratories in the US Pacific Northwest. RESULTS: Responding laboratories (n =
      221) were taking advantage of the availability of waived tests and using them to
      make definitive diagnoses. We found considerable differences between quality
      control practices and the laboratories' perceptions of quality control
      requirements. Most respondents were performing traditional quality control on
      waived tests, influenced by their interpretation of regulations, the intended use
      of the test, and the testing personnel employed. CONCLUSIONS: Technology
      optimized for alternate quality control can represent an improvement in ease of
      use while meeting expectations for accuracy and providing relief from regulatory
      burdens. However, laboratory personnel exhibit confusion in applying new quality
      control systems.

PMID- 10923071
TI  - Whole-blood glucose and lactate. Trilayer biosensors, drug interference,
      metabolism, and practice guidelines.
AB  - OBJECTIVE: To assess the effects of 30 of the most commonly used critical care
      drugs on measurements obtained with trilayer electrochemical biosensors on a
      reference analyzer (ABL625-GL), to determine metabolic changes in glucose and
      lactate in vitro, and to formulate guidelines for whole-blood analysis of these 2
      analytes. DESIGN: Serial measurements were taken of changes in glucose and
      lactate levels caused by metabolism in whole blood in vitro over time. A parallel
      control study of drug interference with measurements of glucose and lactate in
      whole blood and of dose-response relationships in whole-blood samples and in
      plasma samples also was conducted. RESULTS: At room temperature, whole-blood
      metabolism decreased glucose levels -2.3% at 15 minutes, -4.6% at 30 minutes, and
      -6.4% at 45 minutes. Metabolism increased lactate levels 11.4% at 15 minutes,
      20.6% at 30 minutes, and 26.7% at 45 minutes in vitro. Paired differences between
      drug-spiked and control samples were calculated to determine interference
      (corrected for metabolism). The threshold for determination of interference was
      +/-2 SD from within-day precision, equal to +/-0.18 and +/-0.10 mmol/L for
      glucose and lactate, respectively. Only mannitol (C(6)H(14)O(6)) interfered with
      glucose and lactate measurements. At a concentration of 24 mg/mL, mannitol
      decreased whole-blood glucose levels by an average of 0.711 mmol/L (12.8 mg/dL)
      and whole-blood lactate levels by 0.16 mmol/L (1.4 mg/dL). Mannitol interference
      with measurements may have resulted from suppression of hydrogen peroxide
      formation in the enzymatic reactions in the biosensors, repartitioning of water
      between erythrocytes and plasma, or from other mechanisms. CONCLUSIONS: Most
      critical care drugs had no significant effects on the trilayer electrochemical
      biosensors. Whole-blood analysis should be performed within 15 minutes for
      lactate and within 30 minutes for glucose because of metabolism in vitro.
      Mannitol effects on glucose measurements may be clinically significant in
      mannitol-induced acute renal failure and therefore should be considered for
      appropriate diagnosis and treatment of critically ill patients.

PMID- 10923072
TI  - Effects of different hematocrit levels on glucose measurements with handheld
      meters for point-of-care testing.
AB  - OBJECTIVES: To determine the effects of low, normal, and high hematocrit levels
      on glucose meter measurements and to assess the clinical risks of hematocrit
      errors. DESIGN: Changes in glucose measurements between low and high hematocrit
      levels were calculated to determine hematocrit effects. The differences between
      glucose measured with meters and with a plasma glucose method (YSI 2300) also
      were compared. SETTING: Six hand-held glucose meters were assessed in vitro at
      low (19.1%), normal (38.5%), and high (58.3%) hematocrit levels, and at 6 glucose
      concentrations ranging from 2.06 mmol/L (37.1 mg/dL) to 30.24 mmol/L (544.7
      mg/dL). RESULTS: Most systems, regardless of the reference to which they were
      calibrated, demonstrated positive bias at lower hematocrit levels and negative
      bias at higher hematocrit levels. Low, normal, and high hematocrit levels
      progressively lowered Precision G and Precision QID glucose measurements.
      Hematocrit effects on the other systems were more dependent on the glucose
      concentration. Overall, Accu-Chek Comfort Curve showed the least sensitivity to
      hematocrit changes, except at the lowest glucose concentration. CONCLUSIONS: We
      strongly recommend that clinical professionals choose glucose systems carefully
      and interpret glucose measurements with extreme caution when the patient's
      hematocrit value changes, particularly if there is a simultaneous change in
      glucose level.

PMID- 10923073
TI  - Abnormal erythrocyte anion exchange in Alzheimer disease.
AB  - CONTEXT: Several abnormalities have been described in red blood cells of patients
      with Alzheimer disease (AD), but to date none of these has been confirmed by a
      second, independent study. Erythrocyte anion exchange has been reported to be
      abnormal in AD; we have developed a new technique for measuring anion exchange.
      OBJECTIVES: To confirm the abnormality of erythrocyte anion exchange in AD and to
      determine whether the phenomenon has potential for clinical utility. DESIGN:
      Comparison of patients with probable AD to age-matched controls. SETTING:
      University hospital and ambulatory clinic. METHODS: Chloride-bicarbonate exchange
      was measured in erythrocyte ghosts resealed with a fluorescent probe of chloride
      concentration. RESULTS: Erythrocyte anion exchange is abnormal in AD. This
      difference appears in citrate but not EDTA anticoagulant. Mahalanobis's
      generalized distance between the 2 populations is 1.7, and a discriminant
      function derived from our technique classifies 82% of the study population in
      accordance with the National Institute of Neurological and Communicative
      Disorders and Stroke-Alzheimer's Disease and Related Disorders Association
      criteria. Receiver operating characteristic analysis demonstrates the possibility
      of choosing cutoffs with high sensitivity and specificity. CONCLUSIONS:
      Measurement of red blood cell anion exchange may be useful in classifying
      patients with AD. The dependence of this phenomenon on anticoagulant suggests the
      involvement of platelet activation or complement fixation.

PMID- 10923074
TI  - Nuclear localization of E-cadherin expression in Merkel cell carcinoma.
AB  - CONTEXT: Cadherins are cell-cell adhesion proteins that act as tumor suppressor
      genes and have a critical role in cell sorting and tissue formation during
      organogenesis. The pattern of cadherin expression constitutes a useful diagnostic
      and prognostic tool in the evaluation of tumors and for determining the
      histogenesis of tumor cells. We have previously characterized the cell types of
      several tumors based on the expression of individual cadherins. OBJECTIVE: To
      investigate the expression of cadherins in Merkel cell carcinomas. DESIGN:
      Paraffin immunohistochemical analysis of the 3 best-studied cadherins was
      performed on 35 cases of Merkel cell carcinoma. RESULTS: E-cadherin was expressed
      in 34 (97%) of 35 Merkel cell carcinomas examined, N-cadherin was expressed in 22
      (63%) of 35 cases, and P-cadherin was expressed in 15 (43%) of 35 cases. This
      frequency of cadherin expression was similar to a group of small cell and
      neuroendocrine tumors from other primary sites. Interestingly, the localization
      of E-cadherin expression was unique in Merkel cell carcinomas compared with other
      primary neuroendocrine tumors. Merkel cell carcinomas showed marked preference
      for nuclear versus membrane localization, whereas small cell tumors from other
      sites showed fewer cases of nuclear E-cadherin expression. The nuclear
      localization of E-cadherin did not correlate with cadherin-associated protein
      beta-catenin nuclear expression. CONCLUSIONS: Our findings show that E-cadherin
      is the most frequently expressed cadherin in Merkel cell carcinoma, followed in
      frequency by N-cadherin then P-cadherin. The pattern of nuclear E-cadherin
      expression is more frequent for Merkel cell carcinoma than small cell tumors of
      other primary sites. These observations suggest that E-cadherin expression and
      function are altered in Merkel cell carcinoma, and this finding has potential use
      in the differential diagnosis of these tumors.

PMID- 10923075
TI  - Decreased CD10-positive mature granulocytes in bone marrow from patients with
      myelodysplastic syndrome.
AB  - OBJECTIVE: We retrospectively examined the maturation of the granulocytic cell
      lineage in bone marrow specimens from patients with myelodysplastic syndrome
      (MDS) by flow cytometry using both light scatter and surface marker
      characteristics, including CD10 and myeloid lineage-associated antigens.
      PATIENTS: The 7 MDS cases we studied included 2 patients with refractory anemia
      (RA), 3 with RA with ringed sideroblasts, 1 with RA with excess of blasts, and 1
      unclassified case. Another 7 patients matched for age and sex who received bone
      marrow aspirates for lymphoma staging (all negative for lymphoma involvement or
      any other hematologic abnormalities) were selected as the control group. RESULTS:
      The percentage of CD10(+) mature granulocytes was significantly lower in patients
      with MDS than in control patients. Additionally, all patients with MDS had less
      than 50% CD10(+) cells in the granulocytic lineage. In contrast, only 1 of the 7
      control patients had less than 50% CD10(+) cells (P <.01). CONCLUSIONS: These
      results suggest that flow cytometry might be a useful adjunct in the assessment
      of patients with suspected MDS. Further studies to correlate CD10(+) mature
      granulocytes from MDS cases with other benign hematologic disorders are indicated
      to confirm our evaluation.

PMID- 10923076
TI  - Concordance of endotoxemia with gram-negative bacteremia. A meta-analysis using
      receiver operating characteristic curves.
AB  - OBJECTIVE: To apply meta-analysis to compare the concordance between the results
      of 2 types of limulus amebocyte lysate (LAL) assay, gelation (GLAL) and
      chromogenic (CLAL), with the detection of gram-negative bacteremia in patients
      with suspected bacteremia. DESIGN: Meta-analysis using receiver operating
      characteristic-based analytical method. DATA SOURCES: MEDLINE literature search
      and manual reviews of article bibliographies together with direct approaches to
      authors of potentially eligible studies. STUDY SELECTION: The studies that were
      selected had all included at least 10 patients, of whom at least 2 patients were
      diagnosed with gram-negative bacteremia, and all had data available for
      extraction into a contingency table format. RESULTS: Fifty-six studies (28 GLAL
      and 28 CLAL studies) met the inclusion criteria. Studies were stratified by type
      of test (GLAL vs CLAL). Each analysis was repeated with smaller studies excluded.
      There was no difference between the 2 types of LAL assays. Among the CLAL
      studies, there was no difference between studies that did versus those that did
      not use the sepsis syndrome criteria as a basis for patient inclusion. Among 45
      studies for which data on the proportion of non-Enterobacteriaceae were
      available, there was a trend toward higher concordance as this proportion
      increased. CONCLUSIONS: The concordance between the LAL test and the detection of
      gram-negative bacteremia in patients with suspected bacteremia is no higher with
      the CLAL assay than with the original GLAL version. However, the concordance is
      higher among studies with a higher proportion of non-Enterobacteriaceae among the
      gram-negative bacteremia isolates.

PMID- 10923077
TI  - Prevalence and pathogenesis of pancreatic acinar tissue at the gastroesophageal
      junction in children and young adults.
AB  - BACKGROUND: Pancreatic acinar tissue (PAT) at the gastroesophageal junction (GEJ)
      has been reported in 3% of adults with Barrett esophagus (BE) and in 24% of
      healthy subjects. The pathogenesis of this ectopic tissue is controversial. Both
      an acquired metaplastic process in the setting of BE and a congenital abnormality
      have been suggested in adults. OBJECTIVE: To clarify the origin of PAT at the
      GEJ. METHODS: We reviewed material obtained from the GEJ in 69 children and young
      adults. Each specimen was evaluated by 3 levels stained with hematoxylin-eosin
      for the presence of PAT, BE, esophagitis, and gastritis. Selected cases were also
      examined with immunohistochemical stains for lipase, trypsin, and amylase.
      RESULTS: In 16% of the study population, PAT was present at the GEJ and was not
      associated with BE. The prevalence of esophagitis and/or gastritis did not vary
      significantly between patients with and without PAT. CONCLUSIONS: Our data
      suggest that PAT at the GEJ develops independently of inflammation and is,
      therefore, likely to be congenital.

PMID- 10923078
TI  - Bronchocentric granulomatosis with mucus impaction due to bronchogenic carcinoma.
      An association with clinical relevance.
AB  - OBJECTIVE: To describe an unexpected inflammatory process associated with
      malignancy in the lung and to postulate a new mode of pathogenesis. DESIGN:
      Retrospective review of surgical pathologic findings. SETTING: Academic hospital
      pathology department. PATIENTS: Four patients, 2 men and 2 women, ranging in age
      from 45 to 74 years, each of whom had a solitary mass on chest radiographs.
      INTERVENTIONS: Pulmonary lobectomy. MAIN OUTCOME MEASURE: Histopathologic
      identification of bronchocentric granulomatosis. RESULTS: Accompanying a
      bronchogenic carcinoma in each case was a necrotizing chronic granulomatous
      reaction centered around bronchioles that were plugged with mucus, necrotic
      detritus from the tumor, lipid, or a combination of these substances. Eosinophils
      were present in small numbers in one case. The pathologic findings characterize
      bronchocentric granulomatosis. CONCLUSIONS: The presence of bronchocentric
      granulomatosis in the biopsy of a mass does not exclude the presence of an
      accompanying bronchogenic carcinoma associated with obstruction of bronchioles.
      Bronchocentric granulomatosis in some cases may represent an immunologic response
      to tumor detritus or lipid, as well as to mucus impaction.

PMID- 10923079
TI  - Carcinosarcoma of the urinary bladder--an aggressive tumor with diverse
      histogenesis. A clinicopathologic study of 4 cases and review of the literature.
AB  - OBJECTIVE: Carcinosarcomas of urinary bladder are rare malignant neoplasms.
      Seventy-eight cases have been previously described. The histologic composition of
      these tumors is variable, but diagnosis requires the presence of both epithelial
      and mesenchymal malignant components. We report 4 additional cases, with an
      emphasis on unusual histologic features. METHODS: Histologic and
      immunohistochemical examinations were performed on bladder tumors from 4
      patients. Clinicopathologic features of previously reported and current cases
      were reviewed and summarized. RESULTS: Four patients (3 men, 1 woman) age 54 to
      77 years were found to have polypoid masses in the urinary bladder. In all cases,
      histologic examination showed biphasic neoplasms with distinct mesenchymal and
      epithelial components. The morphologic and immunohistochemical characteristics of
      the tumors varied. One of the cases was remarkable for the presence of
      liposarcoma, malignant peripheral nerve sheath tumor, and micropapillary
      urothelial carcinoma. Two of the patients died 2 years after diagnosis, which is
      consistent with the previously reported aggressive nature of urinary bladder
      carcinosarcomas. CONCLUSIONS: Carcinosarcomas of the urinary bladder are rare,
      aggressive malignant neoplasms. To our knowledge, a liposarcomatous component has
      been reported in only 1 case previously, and components of micropapillary
      urothelial carcinoma and malignant peripheral nerve sheath tumor have not been
      reported previously in carcinosarcomas of the urinary bladder. Because of the
      aggressive biologic behavior of these tumors, they should be identified promptly
      and treated appropriately.

PMID- 10923080
TI  - Hyalinizing spindle cell tumor with giant rosettes--a soft tissue tumor with
      mesenchymal and neuroendocrine features. An immunohistochemical, ultrastructural,
      and cytogenetic analysis.
AB  - CONTEXT: Hyalinizing spindle cell tumor with giant rosettes is a recently
      described biphasic neoplasm of soft tissues that shares mesenchymal and
      neuroendocrine features. Its morphologic structure is distinctive, with the
      presence of hyalinized paucicellular foci that are termed rosettes. The cells
      around the latter display positive immunoreactivity for neuroendocrine markers.
      The small number of cases described to date indicates that they tend to be
      localized in the extremities. OBJECTIVE: To describe the clinicopathologic
      features of 2 unusual cases of hyalinizing spindle cell tumor with giant
      rosettes. METHODS AND RESULTS: One tumor was located in the prestyloid
      parapharyngeal space and the second in the left thigh. Both tumors were well
      circumscribed and surrounded by a thin capsule-like fibrous band without
      infiltrating projections. The rosettes were embedded in a spindle cell
      proliferation. Immunohistochemical stains showed positive results for S100
      protein, synaptophysin, CD57, protein gene product 9.5, and neuron-specific
      enolase exclusively in the cells palisading the rosettes. These markers were
      negative in the spindle cell portions of the tumor. The latter were
      immunoreactive for factor XIIIa, vimentin, HAM56, collagen IV, and CD68. Vimentin
      was the only marker shared by the rosette-forming cells and the spindle cells.
      Ultrastructurally, the rosette-forming cells contained neurosecretory granules.
      This study describes the first cytogenetic analysis in this type of tumor
      revealing 2 cell lines, both containing a balanced translocation between
      chromosomes 7 and 16. Follow-up of the patients at 16 and 8 months did not
      disclose evidence of recurrence. CONCLUSIONS: These 2 new cases increase the
      awareness of hyalinizing spindle cell tumor with giant rosettes and demonstrate
      that it is a spindle cell neoplasm of unique cytogenetic rearrangements composed
      of dendritic, histiocytic, and fibroblastic cells admixed with cells that have
      neuroendocrine differentiation.

PMID- 10923081
TI  - The cost-effectiveness of immunohistochemistry.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of immunohistochemistry. DESIGN:
      Using a theoretical decision analytic model, the cost-effectiveness of
      immunohistochemistry was evaluated in different scenarios depicting the
      beneficial use of immunohistochemistry. Data regarding the effectiveness of
      immunohistochemistry were obtained from the medical literature and costs were
      obtained from Allegheny General Hospital. SETTINGS: The scenarios depicted both
      private practice and university patients from which anatomic pathology specimens
      were obtained. Immunohistochemistry was subsequently performed on these
      specimens. MAIN OUTCOME MEASURES: Cost, life expectancy, diagnostic certainty,
      ability to predict prognosis, and cost-effectiveness were evaluated. RESULTS: In
      all scenarios, immunohistochemistry was cost-effective at very low efficacies.
      Assuming a per-antibody cost of $50 and use of a 5-antibody panel,
      immunohistochemistry was cost-effective if it resulted in a 1-year gain of
      population life expectancy in 1 or more of every 200 cases in which it was
      applied. Alternatively, if the gain in diagnostic certainty by using
      immunohistochemistry was 10% and the value placed on a percentage gain in
      diagnostic certainty was $1000, immunohistochemistry was cost-effective if it
      produced this increase in certainty in 1 of every 40 tests. If a life-year was
      valued at $50 000, immunohistochemistry was cost-effective if it resulted in a
      change in patient prognosis of 0.5 years in 1 of every 100 tests. CONCLUSIONS:
      Using theoretical modeling, immunohistochemistry is extremely cost-effective.
      These data have implications in an era of managed care when providers attempt to
      trim laboratory services. Additional studies are needed to evaluate the actual
      practice efficacy of immunohistochemistry.

PMID- 10923082
TI  - Warthin-like papillary carcinoma of the thyroid.
AB  - BACKGROUND: Warthin-like papillary carcinoma of thyroid is characterized by
      distinct papillary formations lined by tumor cells with oncocytic cytoplasm,
      nuclear features of papillary carcinoma, and brisk lymphoplasmacytic infiltrates
      in the papillary stalks. This tumor derives its name from its close resemblance
      to Warthin tumor of major salivary glands. DESIGN: The clinicopathologic features
      of 17 patients with Warthin-like papillary carcinoma were studied. RESULTS:
      Fifteen tumors occurred in women and 2 arose in men (age range, 23-63 years). The
      lesions ranged in size from 3 mm to 2.5 cm. Fine-needle aspiration biopsies were
      performed in 7 cases; 4 were diagnosed as papillary carcinoma, 2 as consistent
      with lymphocytic thyroiditis, and 1 as atypical cells. All 17 tumors were
      confined to the thyroid; 6 showed prominent cyst formation and the remaining
      tumors were solid. In each case, the tumor arose in a background of lymphocytic
      thyroiditis. Nodal metastases were identified in 3 cases; however, none showed
      distant metastases. In 7 cases, foci of papillary microcarcinoma and follicular
      variant of papillary carcinoma were found in other areas of the thyroid.
      CONCLUSIONS: Warthin-like tumors can be mistaken for benign lymphoepithelial
      lesions of the thyroid, Hurthle cell carcinoma, and tall cell variant of
      papillary carcinoma in both fine-needle aspiration and histology specimens.
      Follow-up information on the previously reported cases has suggested that these
      tumors behave similarly to usual papillary carcinoma. The extensive lymphocytic
      infiltration in these tumors and their association with chronic lymphocytic
      thyroiditis may suggest a role for immunological mechanisms in the pathogenesis
      of thyroid tumors.

PMID- 10923083
TI  - Expression of cytokeratins 7 and 20 in carcinomas of the extrahepatic biliary
      tract, pancreas, and gallbladder.
AB  - BACKGROUND: Expression of cytokeratins 7 (CK7) and 20 (CK20) may help distinguish
      the site of origin for metastatic carcinomas. Little is known regarding their
      expression in biliary tract and pancreatic carcinomas. Our aim was to study the
      expression of CK7 and CK20 in these tumors. DESIGN: Fifty-three carcinomas of the
      extrahepatic bile ducts (n = 8), ampulla of Vater (n = 7), gallbladder (n = 11),
      and pancreas (n = 27), were retrieved from the surgical pathology files of the
      University of Massachusetts Medical Center. Formalin-fixed, paraffin-embedded
      sections were immunostained with mouse monoclonal antibodies to CK7 and CK20
      using an avidin-biotin immunoperoxidase technique with microwave antigen
      retrieval. The percentage of cells positive for each antibody was assessed on a
      scale of 0 to 3 (0, <10%; 1+, 10% to 50%; 2+, 51% to 90%; 3+, >90%). RESULTS: The
      majority of carcinomas in all groups were positive for CK7 (CK7+) and negative
      for CK20 (CK20-). Of the CK7+ tumors, the majority of tumors in each group were
      3+ positive. CONCLUSIONS: (1) Carcinomas of the extrahepatic biliary tract and
      pancreas are strongly positive for CK7 and negative for CK20 and can be included
      in the differential diagnosis of other carcinomas with this profile in metastatic
      sites. (2) The CK7/CK20 immunostaining profile will not identify the site of
      origin for tumors with extensive growth in the porta hepatis region.

PMID- 10923084
TI  - National Inventory of Clinical Laboratory Testing Services (NICLTS). Development
      and test distribution for 1996.
AB  - CONTEXT: A statistically valid inventory of the distribution, both geographic and
      by laboratory type, of clinical and anatomical laboratory testing in the United
      States is needed to assess the impact of the Clinical Laboratory Improvements
      Amendments of 1988 and to provide information for other health care and public
      health policy decisions. OBJECTIVE: To present initial US laboratory testing
      volume data compiled by the National Inventory of Clinical Laboratory Testing
      Services. DESIGN: Stratified random sample of laboratories performing testing in
      1996 with data on the number of laboratory tests performed, identified by method
      and analyte. Data were collected by field tabulators (moderate- or high
      complexity laboratories) or through a mail/telephone survey (waived or provider
      performed microscopy laboratories) for each site. PARTICIPANTS: Laboratories that
      were enrolled in the 1996 Online Certification Survey and Reporting System,
      maintained by the US Health Care Finance Administration, and that performed
      laboratory testing during 1996. MAIN OUTCOME MEASURE: Laboratory testing
      distribution for 1996 in the United States by analyte, method, and specimen type.
      RESULTS: An overall response rate of 79% provided data from 757 moderate- or high
      complexity laboratories and 1322 waived or provider-performed microscopy
      laboratories. The estimated total US testing volume for 1996 was 7.25 +/- 1.09
      billion tests. Laboratories performing complex testing, defined as greater than
      16 method/analyte/specimen type combinations, comprised 16% of the US
      laboratories by survey site, but performed 80% (95% confidence limits, 43% to
      100%) of the testing volume. Glucose analysis was the most frequently performed
      test. Automated hematology and chemistry analyzers were the most frequently used
      methods. CONCLUSIONS: A statistically valid, consistent survey of the
      distribution of US laboratory testing was obtained. Simple analysis of these data
      by laboratory type and geographic region can provide insights into where
      laboratory testing is performed. The study design allows extensions that will
      facilitate collection of additional data of importance to public health and
      medical care delivery.

PMID- 10923085
TI  - Inflammatory pseudotumor of the renal pelvis. A report of 2 cases with
      clinicopathologic and immunohistochemical study.
AB  - We describe 2 cases of inflammatory pseudotumor of the renal pelvis. Case 1, the
      male patient, was 37 years old, and case 2, the female patient, was 54 years old.
      Both patients presented with macroscopic hematuria and flank pain. Computed
      tomographic (CT) scan and ureterocystoscopy revealed in case 1 a mass in the left
      renal pelvis and the calyces. In case 2, urography showed a lacuna of the renal
      pelvis, and CT scan showed an irregular thickening of the renal pelvis. In both
      cases, the preoperative clinical diagnosis was urothelial carcinoma, and both
      patients underwent nephrectomy. Microscopic examination revealed in case 1 a
      tumor of the renal pelvis composed of spindle cells with eosinophilic cytoplasm
      in a myxoid and vascular stroma with abundant inflammatory infiltrate. In case 2,
      the tumor was composed of densely basophilic spindle cells in a fascicular
      pattern intermingled with lymphocytes and plasma cells and involving the lamina
      propria of the renal pelvis. The spindle cells reacted strongly with antibody to
      vimentin and focally with antibodies to smooth muscle actin and muscle-specific
      actin. In the urogenital tract inflammatory pseudotumor involves preferentially
      the urinary bladder. Rare cases have been reported in the kidney. The 2 cases
      presented here are unusual due to the location in the renal pelvis, mimicking
      urothelial carcinoma.

PMID- 10923086
TI  - Primary T-cell-rich B-cell lymphoma of the ethmoid sinus. A case report with 5
      years of follow-up.
AB  - T-cell-rich B-cell lymphoma (TCRBCL) is an uncommon and recently recognized
      variant of B-cell non-Hodgkin lymphoma characterized by a few large neoplastic B
      cells amid a predominant population of reactive T lymphocytes and variable
      numbers of histiocytes. Morphologically, TCRBCL resembles a variety of non
      Hodgkin lymphomas and Hodgkin disease. Accurate diagnosis and proper treatment
      are essential to assure a favorable prognosis. To our knowledge, this is the
      first report of ethmoid sinus presentation of TCRBCL in an Epstein-Barr virus
      negative 51-year-old man. Combined chemotherapy and radiotherapy were
      administered based on the correct diagnosis. The patient has had a complete
      response with no recurrence during the 5-year follow-up.

PMID- 10923087
TI  - Nuchal fibrocartilaginous pseudotumor in a 10-year-old girl.
AB  - We report a case of a 10-year-old girl who, 4 years after a trauma to the neck,
      developed a soft tissue mass in the midline at the C5-6 level. The lesion was not
      attached to the bone and was composed of fibrocartilaginous tissue, similar to
      the nuchal fibrocartilaginous pseudotumor, a rare, recently reported condition
      that has been described in the medical literature in only 4 cases, all of them
      adults.

PMID- 10923088
TI  - Ciliocytophthoria in clinical virology.
AB  - Direct immunofluorescence assays (DFAs) are used in the clinical virology
      laboratory for the rapid detection of viruses. An assessment of the cellularity
      of specimens submitted for DFA is necessary for the most effective use of this
      assay. This assessment ensures that an adequate number of the appropriate cells
      are present for examination. During this assessment, clinical virologists may
      encounter unfamiliar cellular elements or cellular fragments. One of these
      elements, ciliocytophthoria, has been misinterpreted as a parasite in specimens
      submitted for cytologic testing. We describe a similar case in which a
      technologist thought that ciliocytophthoria possibly represented a ciliated
      parasite in a nasopharyngeal specimen sent for respiratory syncytial virus DFA.
      After a thorough morphologic examination, the staff dismissed the possibility of
      a ciliated parasite. We confirmed this entity as ciliocytophthoria using
      morphologic criteria and the Diff-Quik stain. This near misidentification of
      ciliocytophthoria as a ciliated parasite affords us the opportunity to raise the
      awareness of clinical virologists about ciliocytophthoria. Additionally, we
      briefly review useful features for differentiating ciliocytophthoria from the
      only ciliate parasitic for humans, Balantidium coli. Finally, we present the
      utility of a commonly used cytologic stain, the Diff-Quik stain, for the
      confirmation of ciliocytophthoria.

PMID- 10923089
TI  - Intravascular papillary endothelial hyperplasia in a vascular lesion of the
      paranasal sinus.
AB  - Intravascular papillary endothelial hyperplasia (IPEH) is usually a cutaneous
      lesion thought to represent a peculiar manifestation of an organizing thrombus.
      The principal significance of IPEH is its microscopic resemblance to angiosarcoma
      and possible misinterpretation as such. The occurrence of IPEH in the paranasal
      sinus is exceedingly rare. In this article, we report the first case to our
      knowledge of IPEH in a vascular lesion that originated from the ethmoid sinus and
      extended into the sphenoid sinus and sella. Despite the benign nature of this
      lesion, it could have been mistaken for a malignant tumor because of its clinical
      course and radiologic findings.

PMID- 10923090
TI  - Myelophthisis as a solitary manifestation of failure from rectal carcinoma. A
      Batson phenomenon?
AB  - Rectal carcinoma is uncommonly associated with systemic metastases in the absence
      of liver metastases, reflecting the predilection for spread via the portal
      system. Occasionally, isolated lung metastases are seen, which are usually
      attributed to spread via the portosystemic anastomoses in the distal rectum.
      However, myelophthisis is an unreported complication of rectal cancer as an
      isolated form of systemic failure. We present a case of fatal myelophthisis
      associated with otherwise localized rectal carcinoma secondary to metastatic
      rectal cancer. This observation led to the hypothesis that spread to the bone
      marrow occurred via a "third circulation," the Batson plexus, a network of deep
      pelvic veins with rich anastomoses to the vertebral plexus.

PMID- 10923091
TI  - A case report of ascariasis of the common bile duct in a patient who had
      undergone cholecystectomy.
AB  - This is a case report of ascariasis of the common bile duct in a 65-year-old man
      from Colombia who had undergone prior cholecystectomy. The patient presented with
      postprandial epigastric pain and a 20-lb weight loss. The laboratory findings
      were remarkable for peripheral blood eosinophilia. The ultrasound finding was
      suggestive of periampullary or pancreatic neoplasm. He underwent endoscopic
      retrograde cholangiopancreatography with endoscopic extraction of a motile, live
      worm identified as Ascaris lumbricoides. Roundworm infestation should always be
      suspected in immigrants from endemic areas who present with hepatobiliary
      symptoms.

PMID- 10923093
TI  - Pathologic quiz case. A nodule on the back. Pathologic diagnosis: proliferating
      trichilemmal tumor.

PMID- 10923092
TI  - Primary bilateral mucosa-associated lymphoid tissue lymphoma of the breast with
      atypical ductal hyperplasia and localized amyloidosis. A case report and review
      of the literature.
AB  - Primary non-Hodgkin lymphoma of the breast is a rare disease. Primary mucosa
      associated lymphoid tissue lymphoma is even rarer, and bilateral involvement is
      exceptional. We describe a case of primary bilateral breast mucosa-associated
      lymphoid tissue lymphoma with bilateral atypical ductal hyperplasia and bilateral
      localized amyloidosis in a 64-year-old woman with a history of arthritis and
      systemic lupus erythematosus and its clinical, histologic, and
      immunohistochemical features. Microscopic examination of the breast lesion showed
      dense periductal and perilobular small and plasmacytoid lymphocytes with
      eosinophilic amyloid in the vessels and the stroma. Bilateral single foci of
      atypical ductal hyperplasia were also noted. Fine needle aspiration showed small
      and large lymphocytes and plasma cells. Molecular analysis demonstrated a heavy
      chain immunoglobulin H gene rearrangement. Flow cytometry studies showed an
      abnormal B-cell population. The combined histologic, paraffin
      immunohistochemistry, flow cytometry, and molecular results were considered
      diagnostic for low-grade mucosa-associated lymphoid tissue lymphoma. The patient
      underwent bilateral local breast radiation without other organ or site
      involvement.

PMID- 10923094
TI  - Pathologic quiz case. A 14-year-old boy with splenomegaly. Pathologic diagnosis:
      Gaucher disease.

PMID- 10923095
TI  - Human T-lymphotropic virus 1 adult T-cell lymphoma with Giardia and Strongyloides
      parasitism.

PMID- 10923097
TI  - Docetaxel and gemcitabine in anthracycline-resistant advanced breast cancer: a
      Hellenic Cooperative Oncology Group Phase II study.
AB  - A phase II study was conducted to evaluate the activity and toxicity profile of
      the combination of docetaxel and gemcitabine in anthracycline-resistant advanced
      breast cancer (ABC). Thirty-nine eligible patients with a median performance
      status of 1 (range, 0-2) were enrolled in the study. Treatment consisted of
      docetaxel 75 mg/m2 in a 1-hr infusion on day 1 preceded by gemcitabine 1000 mg/m2
      over 30 min on days 1 and 8. One hundred eighty-one treatment cycles were
      administered, 113 (62.4%) of them at full dose. Relative dose intensity of
      gemcitabine and of docetaxel was 0.73 and 0.85, respectively. More common grade 3
      4 toxicities included neutropenia (49%), anemia (10%), fatigue (10%),
      nausea/vomiting (8%), and alopecia (77%). Seven patients were hospitalized for
      febrile neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration
      was required in 90% of patients. Overall, 14 patients (36%) responded, 3 (7.5%)
      of them completely. Median duration of response was 10.3 months (range, 4.6
      17.5+). Median time to progression was 7 months (range, 0.2-17.5+) and median
      survival 12.7 months (range, 2-20.5+). In conclusion, the combination of
      docetaxel and gemcitabine, as used in the present study, has moderate activity in
      anthracycline-resistant ABC. Future studies should incorporate prophylactic
      administration of G-CSF to reduce the incidence of febrile neutropenia and
      maintain dose intensity.

PMID- 10923098
TI  - A retrospective analysis of postradiation chemotherapy in 133 patients with
      glioblastoma multiforme.
AB  - The impact on survival of postradiation nitrosourea-containing chemotherapy (CHT)
      in patients with glioblastoma multiforme (GM) was analyzed retrospectively in 133
      patients who completed the planned radiotherapy out of 173 observed cases. Thirty
      five patients were < 50 years old, 89 were males, 20 had performance status (PS)
      < 70 and 72 > or = 70. Surgery was followed by radiotherapy in all cases (50-60
      Gy in 95 patients, 61-70 Gy in 38 patients). At the end of radiotherapy, 43
      patients received CHT, whereas 90 patients did not receive further therapy. At
      univariate analysis, age < 50 years, feminine gender, subtotal or total
      resection, radiotherapy doses > 60 Gy, and CHT had an independent prognostic
      value. Our results suggest that chemotherapy improves 2-year survival rates from
      12% to 28% in GM. The sequence of treatment, new drugs, and combinations should
      be further explored.

PMID- 10923099
TI  - Dihydropyrimidine dehydrogenase activity in human pancreatic tumor tissues.
AB  - Dihydropyrimidine dehydrogenase (DPD) activity was investigated using pancreatic
      tumors and normal pancreatic tissues surrounding the tumors obtained from 12
      patients with pancreatic cancer. The mean DPD activity (+/- SD) was 2.69 +/- 1.88
      nmol/mg protein/hr in normal pancreatic tissue and was 6.59 +/- 5.36 nmol/mg
      protein/hr in pancreatic tumor tissues. The DPD activity in tumor tissue was two-
      to threefold higher (p < 0.01) than that in normal tissue, but no marked
      difference was observed in DPD activity among cancer stages. The DPD activity of
      pancreatic tumors may be a useful clinical marker of the responsibility of
      fluorinated pyrimidine dosing in pancreatic cancer.

PMID- 10923100
TI  - A prospective pharmacologic evaluation of age-related toxicity of adjuvant
      chemotherapy in women with breast cancer.
AB  - Despite increasing evidence of benefit from adjuvant chemotherapy, older women
      with breast cancer are commonly given less aggressive treatment than younger
      patients. Conflicting prior data regarding age-related toxicity prompted this
      prospective study. Forty-four women (aged 35-79 years) with early-stage breast
      cancer were treated with four cycles of adjuvant therapy with doxorubicin 60
      mg/m2 i.v. and cyclophosphamide 600 mg/m2 i.v. every 21 days. They were monitored
      for myelosuppression, cardiotoxicity, and decrease in quality of life.
      Pharmacokinetics were analyzed using cycle 1 plasma samples. Bone marrow
      granulocyte and macrophage colony-forming units (CFU-GM) were assayed in vitro
      for dose response to 4-hydroperoxycyclophosphamide and doxorubicin before cycle
      1. There was moderate evidence of age-related decrease in nadir absolute
      neutrophil count (ANC) when age was viewed as a continuous variable. On average
      there was a 10/microliter drop in cycle 1 nadir ANC for every year increase in
      age (p = 0.02). However, when age was viewed as a categorical variable (age < 65
      vs. > or = 65 years), a similar proportion of women in each group reached an ANC
      < 100 (18% vs. 19%). Neither neutropenic complications, alteration in cardiac
      function, nor change in quality of life scores were significantly age related (p
      > 0.12). Pharmacokinetic analyses did not demonstrate age-related differences in
      the clearance of either doxorubicin or cyclophosphamide (p > 0.8).
      Pharmacodynamic analysis of individual patient bone marrow progenitor cell
      sensitivity did not reveal any correlation with age (p > 0.48). In women
      undergoing adjuvant therapy for breast cancer, no clinically significant age
      related trends in toxicity were observed. These data suggest that older age alone
      should not exclude patients from receiving adjuvant therapy with doxorubicin and
      cyclophosphamide.

PMID- 10923101
TI  - Tumor-infiltrating B-cell-derived IgG recognizes tumor components in human lung
      cancer.
AB  - Tumor-infiltrating lymphocytes consist predominantly of T cells, whereas B cells,
      plasma cells, and natural killer cells are observed with different degrees of
      frequency. We investigated the nature of tumor-infiltrating B lymphocytes (TIB)
      in human lung cancer. First, to examine the ability of immunogloblin production
      by TIB, cancer tissues were subcutaneously transplanted in severe combined
      immunodeficient mice, and the murine serum was examined for the concentration of
      human immunogloblin. Human IgG (huIgG) was detected in the serum of all 12 mice
      engrafted with lung cancer tissues. huIgM was almost undetectable. The levels of
      huIgG reached a peak approximately 6 weeks after engraftment and gradually
      decreased but were detectable until 20 weeks postengrafment. Serum from a large
      cell carcinoma-engrafted mouse reacted with a protein of 60 kDa derived from lung
      cancer cell lines (PC-9, Sq-1) and autologous tumor cells but did not react with
      cell lysates of normal lung tissue. Serum from an adenocarcinoma-engrafted mouse
      reacted with two proteins, 33 and 55 kDa, derived from lung cancer cell lines (PC
      9, Sq-1, A549) and autologous tumor cells but did not react with the lysate of
      normal lung tissues. These results suggest that B cells infiltrating lung cancer
      tissues produce IgG that recognizes common tumor-specific antigen.

PMID- 10923102
TI  - Accelerated hyperfractionation in patients with non-small cell bronchogenic
      cancers as a cost-effective and user- and patient-friendly schedule.
AB  - We developed an accelerated hyperfractionation schedule with acceptable effect
      and toxicity in non-small cell bronchogenic carcinomas. An evolutionary
      institutional pilot was initiated in March 1995 as a modification of Radiation
      Therapy Oncology Group (RTOG) 9205, thrice-daily fractionation schedule. Twenty
      nine patients with bronchogenic and 7 with head and neck cancers had treatment
      initiated and completed. A dose of 1.2 Gy was delivered to a mediastinal plus
      tumor field concomitantly with synchronous boost of 0.6 Gy to a limited volume of
      gross tumor (twice daily for 21 treatments days in 4 weeks) with a total dose
      being 75.60 Gy to the primary gross tumor and 50.4 Gy to the elective volume. The
      bronchogenic cancers were stages IB (medically unresectable, n = 3), IIB (n = 4),
      IIIA (n = 4), or IIIB (n = 18). Eleven patients had squamous cell cancers, 13
      adenocarcinomas, 1 large cell, and 2 carcinomas not specified. With 12 months
      median follow-up, tolerance has been excellent without any patient complaining of
      at least Oncology Nursing Society (ONS) grade 3 esophagitis; treatment
      interruptions occurred in only one patient after 8 days. Weight loss occurred in
      12 patients, averaging 4.8% for these patients and 2% overall. Seven patients had
      a complete response and 20 a partial response. Median survival was 12 months, 1
      year survival 58%, 2-year 21%, and 3-year 18%. Seven patients with bronchogenic
      cancer are still alive. Seven head and neck cancer patients were treated, in
      which five had base of tongue tumors stage T2 to 4, N0 to N1. Pharyngitis and
      mucositis were problematic in at least four patients. The outcomes are comparable
      with other RTOG experience. Hyperfractionated synchronous concomitant boost of
      total tumor dose to 75.6 Gy in 4 weeks for bronchogenic patients was well
      tolerated and acceptable to physicians and patients.

PMID- 10923103
TI  - Growth factor receptor tyrosine kinases: cell adhesion kinase family suggests a
      novel signaling mechanism in cancer.

PMID- 10923104
TI  - New molecular strategies for early lung cancer detection.

PMID- 10923105
TI  - Managing the neurotoxicity of paclitaxel (Taxol) and docetaxel (Taxotere) with
      neurotrophic factors.

PMID- 10923106
TI  - Burkitt's lymphoma: molecular pathogenesis and treatment.

PMID- 10923107
TI  - Epidemiology of cervical cancer.

PMID- 10923108
TI  - Cell-cell and cell-extracellular matrix adhesion molecules communicate with
      growth factor receptors: an interactive signaling Web.

PMID- 10923109
TI  - Medibank, 25 years on: looking back, looking forward.

PMID- 10923110
TI  - The alternative national health programme.

PMID- 10923111
TI  - Medibank: from conception to delivery and beyond.

PMID- 10923112
TI  - Down a different path in Melbourne: how Medibank was conceived.

PMID- 10923113
TI  - Medibank: looking back after 25 years.

PMID- 10923114
TI  - They can't say they weren't warned!

PMID- 10923115
TI  - The Medibank campaign.

PMID- 10923116
TI  - Medibank and the Doctors Reform Society.

PMID- 10923117
TI  - The battle to put Medibank in place.

PMID- 10923118
TI  - Medibank and rural general practice.

PMID- 10923119
TI  - Medibank remakes general practice.

PMID- 10923120
TI  - Medibank and the decline of general practice.

PMID- 10923121
TI  - Medibank and the physician.

PMID- 10923122
TI  - Medibank and Medicare: a case for surgery.

PMID- 10923123
TI  - The impact of Medibank on surgical practice.

PMID- 10923125
TI  - Medicare: options for the next 25 years.

PMID- 10923124
TI  - Increased capability, diminished possibility.

PMID- 10923126
TI  - Medicare's maturity: shaping the future from the past.

PMID- 10923127
TI  - The future of Medicare and health service financing.

PMID- 10923128
TI  - Medicare: diagnosis and prognosis.

PMID- 10923129
TI  - [Increase of troponin I during acute pericarditis. 69 cases at an emergency
      service].
AB  - OBJECTIVE: The purpose of this study was to determine the incidence and
      significance of troponin i (tni) elevation in acute pericarditis. PATIENTS AND
      METHODS: We retrospectively included 69 patients with acute idiopathic
      pericarditis. We analyzed ECG recordings, echocardiography findings and tni
      level. Thirty-four patients (49%) had detectable tni (> 0.5 ng/ml), 15 (22%) had
      a significantly elevated level (> 1.5 ng/ml). There was a significant correlation
      between elevated tni level and ST elevation. All patients were well at one year.
      CONCLUSIONS: A rise in tni is frequently observed during acute idiopathic
      pericarditis. According to the correlation with ST segment elevation, a rise in
      tni is apparently indicative of superficial myocardial damage. The prognostic
      value remains unknown.

PMID- 10923130
TI  - [Drug tests on 198 drivers involved in an accident].
AB  - OBJECTIVES: A prospective analytical study was performed in a large population of
      drivers implicated in traffic accidents to determine the significance of drug
      levels observed in blood, urine, saliva and sweat and which assays are best to
      perform in each sample. METHODS: Samples of blood (7.5 ml), urine (10-20 ml),
      saliva (salivette Sarstedt) and sweat (cosmetic pad spiked with water
      isopropanol) were systematically collected in drivers implicated in non-fatal
      traffic accidents from March to November 1999. The samples were tested for
      pharmaceuticals (barbiturates, benzodiazepines, anti-depressants, neuroleptics,
      antiepileptics and antihistamines) and for drugs of abuse by hyphenated
      chromatographic methods (LC/DAD, GC/MS and LC/MS). RESULTS: A total of 198
      drivers (bicycle, motorbike, car, truck) were tested (age range 13-57 years, 82%
      males). Blood alcohol was positive in 27 cases (13.7%), ranging from 0.11 to 3.19
      g/l (mean 1.49 g/l), being > 0.5 g/l in 21 cases. Cannabis was the most
      frequently observed illicit drug (9.6% of the cases). Its formal pharmacological
      effect could only be documented by blood testing using GC/MS. Even in the
      hospital setting, urine collection was difficult. In 16% of the cases, this fluid
      was missing. Parent compounds were excreted in both saliva and sweat. On-site
      devices devoted to urine and metabolites were inapplicable. Concentrations in
      sweat and saliva were very low, particularly for benzodiazepines and cannabis.
      There was also a risk of external contamination for sweat. CONCLUSION: Saliva
      might be a good substitution fluid for blood for sample taking on the road side.

PMID- 10923131
TI  - [Capillary hyperpermeability syndrome of the face].
AB  - BACKGROUND: Capillary leak syndrome is a rare disorder, with various clinical
      features, characterized by episodes of diffuse edema. CASE REPORT: We report the
      case of a 83 year-old woman with capillary leak syndrome of the face
      characterized by recurrent episodes of edamata. We found a follicular non
      Hodgkin's lymphoma and high levels of plasma interleukin (IL) 2 and IL 6.
      Regression of edema and remission of hematology disease have been obtained with
      corticoids and chloraminophene. DISCUSSION: This case illustrates that capillary
      leak syndrome may present as an edema of the face and may be in some cases
      considered as a paraneoplastic syndrome. The role of cytokines seems important.
      This case suggests that corticoids may be useful in the management of neoplasm
      induced capillary leak syndrome.

PMID- 10923132
TI  - [First report of coccidioidomycosis associated with Sweet syndrome].
AB  - BACKGROUND: We describe the first reported case associating coccidioidomycosis
      and Sweet syndrome, two uncommon diseases in Europe. CASE REPORT: One month after
      traveling to Mexico, a 47-year-old woman developed a maculo-papulous rash on her
      trunk, neck and limbs. She also had cough, associated with signs of an upper
      respiratory tract infection and weight loss. Sweetis syndrome was first diagnosis
      and confirmed histologically on a skin lesion biopsy. An aspectific pulmonary
      infiltrate, associated with a left-sided paracardiac opacity was found on chest X
      rays and the CT scan. Bronchoalveolar lavage products contained more than 60%
      lymphocytes. Serology using coccidioidin showed an F-precipitin on agar (IgM) and
      an IgG-titre of 1:8, leading to the diagnosis of primary Coccidioides immitis
      infection with a probable lung localization. DISCUSSION: Search for an associated
      disease should be made in patients with Sweet syndrome. The Sweet syndrome
      coccidioidomycosis association could be related to TH-1 lymphocyte proliferation.

PMID- 10923133
TI  - [Generalized livedo during severe chloralose poisoning].

PMID- 10923134
TI  - [St. Johns wort-venlafaxine interaction].

PMID- 10923135
TI  - [Beware of fungi].

PMID- 10923136
TI  - [Acute Mycoplasma pneumoniae infection: new cause of Gianotti Crosti syndrome].

PMID- 10923137
TI  - [Liver transplantation: the problem of peroperative bleeding].

PMID- 10923138
TI  - [Quality standards in ambulatory medicine. Can the experience acquired in the
      industrial setting be applied to the training of physicians?].

PMID- 10923139
TI  - [Recommendations for the management of patients with skin melanoma].

PMID- 10923140
TI  - [Significance of pharmacoeconomics].

PMID- 10923141
TI  - [Role of hysteroscopy in the diagnosis and treatment of infertility].
AB  - UTERINE DISORDERS: Because they can prevent implantation, anomalies within the
      uterine cavity play an important role in fertility. The uterine disorders most
      often observed during hysteroscopy and implicated in infertility are adhesions,
      septa, polyps, submucous myomas, adenomyosis, endometritis, anomalies of the
      cervical canal, and lesions of the uterotubal junction. EXPLORATIONS:
      Hysterosalpingography can be used to evaluate tubal permeability but provides
      inadequate information about the uterine cavity (numerous false-positives and
      false-negatives). Pelvic ultrasound is especially helpful for diagnosing
      interstitial anomalies in the uterus. HYSTEROSCOPY: Diagnostic hysteroscopy also
      has a place in infertility investigations, for it allows direct visualization of
      the uterine cavity, the endometrial mucus (endometritis, adenomyosis), and the
      cervical canal. The examination is practiced on a out-patient basis, without
      anesthesia, using appropriate small-caliber instruments and irrigation with
      physiological saline. Surgical hysteroscopy is used to treat these anomalies.
      Patients receive general anesthesia. A high-frequency, low-voltage electric
      current is used, and glycine for irrigation. This procedure allows resection of
      submucous myomas and polyps and of septa and adhesions. Some groups use laser
      beams and irrigation by physiological saline for these treatments. Coagulation of
      a superficial focal spot of adenomyosis is not useful in infertility therapy.
      RESULTS: As assessed by the percentage of patients with each indication who
      subsequently became pregnant, the results of surgical hysteroscopy have been
      satisfactory: 62 per cent (%) of cases after myomectomy, 66% after section of
      uterine septa, and 61% after treatment of complicated adhesions. A new
      exploration of the uterine cavity will be necessary sometime after the surgery to
      verify the absence of any iatrogenic disorders (adhesions, myomatous fragments).

PMID- 10923142
TI  - [Subacute cutaneous lupus erythematosus].
AB  - SKIN LESIONS: The concept that patients with subacute cutaneous lupus
      erythematosus (SCLE) skin lesions represent a distinct lupus erythematosus subset
      was proposed in 1979 by Sontheimer and supported by many studies. Skin lesions
      are papulo-squamous, psoriasiform or annular. Photosensitivity is a common
      complaint and photo-reproduction is significantly frequent in these patients.
      They persist for weeks or months and typically heal without atrophy or scarring
      with hyperpigmentation or more often hypopigmentation. SYSTEMIC INVOLVEMENT:
      Systemic disease is generally quite mild and the prognostic is usually
      favourable. High-titer, precipitating antibodies to Ro/SSA and HLA DR2 and/or HLA
      DR3 are strongly associated with SCLE. In some observations, the relation-ship
      between SCLE and drugs has been recognized. TREATMENT: Antimalarial agents are
      first line systemic treatment. Other therapies, including Thalidomide are helpful
      for patients with resistant disease. The pathomechanisms of photosensitive SCLE
      involved antigens Ro/SSA, epidermal and dermal cytokines, intercellular adhesion
      molecules, mononuclear cells.

PMID- 10923143
TI  - [Standards, options, and recommendations for the management of patients with skin
      melanoma. National Federation of Centers for the Fight against Cancer].

PMID- 10923144
TI  - [Treatment of non-small cell lung cancer].

PMID- 10923145
TI  - [Decreasing prevalence of Helicobacter pylori: a consequence of treatment of
      gastroduodenal ulcers].
AB  - Four patients with gastroduodenal ulcers in the absence of Helicobacter pylori
      illustrate the decreasing prevalence of this microorganism. One was a 19-year-old
      boy with nausea, diarrhoea and weight loss caused by multiple gastroduodenal
      ulcers due to the Zollinger-Ellison syndrome. Another was a 36-year-old man with
      abdominal discomfort caused by an ulcer due to Crohn's disease. The other two
      cases concerned a 29-year-old man and a 68-year-old woman with relapsing ulcer
      disease and active bleeding, in whom no causal factors could be determined.
      Recent studies suggest a decreasing prevalence of H. pylori leading to both a
      relative and an absolute decrease of gastroduodenal ulcers attributed to H.
      pylori. Future treatment strategies will have to take these altered prevalence
      rates into consideration.

PMID- 10923146
TI  - [Preoperative outpatient evaluation of young adults by anesthesiologist:
      anamnesis and physical examination are satisfactory--short questionnaire of Dutch
      Public Health Council is not].
AB  - The report of the Netherlands Health Council 'Preoperatief onderzoek; een
      herijking van uitgangspunten' recommends that the health status of patients aged
      16-39 years can be investigated preoperatively by the anaesthesiologist using a
      short questionnaire (6 questions). However, it is not clear whether such an
      abbreviated preoperative investigation will be informative enough for a safe and
      balanced anaesthesiologic management. An overview of relevant literature on the
      subject of preoperative investigation indicates that the preoperative physical
      status of patients as reflected by the American Society of Anesthesiologists
      (ASA) classification is a predictor of perioperative complications. Patients can
      be classified accordingly on the basis of an extended history and physical
      examination only: any routine additional investigation, such as ECG, chest X-ray
      or laboratory investigations, seem superfluous. Only blood group, rhesus factor
      and the presence of irregular antibodies may need to be determined if indicated
      by the kind of surgery. Currently, however, there is not sufficient evidence to
      demonstrate that the short questionnaire of the Netherlands Health Council is
      informative enough.

PMID- 10923147
TI  - [Practice of systematic reviews. VII. Pooling of results from observational
      studies].
AB  - Knowledge concerning aetiologic hypotheses can be obtained through systematic
      reviews of observational studies. In observational studies, heterogeneity between
      studies is expected, because of differences in study design and analysis. Data
      from observational studies have to be made comparable before pooling of results
      from component studies is possible. In this, definition of exposure and disease
      and adjustment for confounding have to be taken into account. Three methods to
      deal with heterogeneity are presented: ignoring (fixed effects model), modelling
      (random effects model) and exploring (meta regression). Any combination of data
      in meta-analysis of observational studies has to be based on statistical,
      methodological and clinical considerations. The same considerations are applied
      for the choice which method is used.

PMID- 10923148
TI  - [Use of angiotensin-II-antagonists in hypertension].
AB  - Angiotensin-II antagonists act on the terminus of the renin-angiotensin cascade,
      i.c. the angiotensin II subtype I (AT1) receptor. As a result, the receptor is
      reversibly blocked for the action of circulating angiotensin II, usually for 24
      hours after a single dose. The consequence of this is that the blood pressure
      decreases, to the extent that this is dependent upon the action of this hormone.
      This action has various components, namely, vasoconstriction, sodium retention
      (mainly via aldosterone) and the promotion of cell growth in the cardiovascular
      system. The decrease in blood pressure is comparable to that achieved with the
      conventional antihypertensive drugs. The most striking difference is the almost
      total absence of the adverse effects know to be produced by the established
      agents. In vivo, there is no significant difference between the activity of the
      various AT1-receptor blockers. Their ultimate effect on the cardiovascular
      prognosis in the hypertensive population is still under investigation.

PMID- 10923149
TI  - [Reimplantation of aortic valve; preliminary results in 13 patients].
AB  - OBJECTIVE: To evaluate our initial experience with the reimplantation technique
      of the aortic valve. DESIGN: Retrospective. METHOD: From January 1st 1998 to
      January 31st 2000, 13 patients were operated on by the technique as described by
      David. Mean age was 52.2 years (SD: 11). Median preoperative New York Heart
      Association (NYHA) functional class was 2/4 and median preoperative degree of
      aortic regurgitation was 3/4. Surgical indications were initially limited to
      aneurysmal disease of the aortic root (n = 6) and ascending aorta (n = 4), all
      complicated by aortic regurgitation. Later on, we also applied the technique in
      type A aortic dissection (n = 3). The repair was evaluated peroperatively by
      transoesophageal and postoperatively, by transthoracic echocardiography. The
      patients were followed postoperatively in the outpatient department. RESULTS: No
      technical problems arose that necessitated change or adjustment of the technique.
      Mean cardiac arrest time was 184 min (SD: 40) and cardiopulmonary bypass time 254
      min (SD: 74). The primary aetiology on histopathological examination was medial
      necrosis in 5 patients and degenerative disease in the others. There was no early
      nor late mortality and none of the patients was reoperated upon the aortic root.
      Follow-up was complete at a mean of 12.3 months (SD: 8). Median aortic
      regurgitation at follow-up was 0.5 (p = 0.0001 versus preoperative) and median
      NYHA functional class at follow-up was 1 (p = 0.02 versus preoperative).
      CONCLUSION: David's aortic valve reimplantation technique was carried out with a
      low surgical risk and a low degree of residual aortic regurgitation in aneurysm
      of the aortic root, aneurysm of the ascending aorta and type A dissection with
      major destruction of the aortic root.

PMID- 10923150
TI  - [Embolization of skeletal metastases in patients with differentiated thyroid
      carcinoma].
AB  - Treatment options in patients with bone metastases of differentiated thyroid
      carcinoma are limited and mostly aimed at palliation. Conventional treatment
      modalities are: radioiodine therapy, surgery or external irradiation. A lesser
      known option is selective embolization of tumour metastases. During selective
      catheterization of the arteries that feed the metastases embolization material
      (e.g. polyvinyl alcohol particles) is injected into the local vasculature under
      radiographic control. The embolization is immediately evaluated angiographically.
      This therapy was used in three patients with differentiated thyroid carcinoma, a
      60-year-old man suffering from back ache, paresis and afterwards paralysis of the
      lower body parts with incontinence, and in two women aged 59 years (suffering
      from diplopia and a pelvic metastasis) and aged 27 years (suffering from
      neurological symptoms or pain of the right leg due to a pelvic metastasis). In
      all three the symptoms disappeared after the embolization and ensuing treatment
      with radioactive iodine. Due to recurrent increase in serum thyroglobulin
      concentration repeated re-embolization was necessary, but during a follow-up
      period of 3-5 years the palliation remained adequate. Selective embolization
      appears to be a safe and efficacious treatment, with good tolerability for the
      patient. Embolization alone or preferably preceded by radioiodine therapy may
      lead to decreased tumour progression and often gives rise to immediate relief of
      symptoms.

PMID- 10923151
TI  - [Fever of unknown origin caused by the adult form of Still's disease].
AB  - In three patients, two women aged 70 and 19 years and a man aged 33 years with
      long-lasting fever no diagnosis was made after extensive diagnostic work-up.
      After exclusion of infectious, malignant and rheumatic diseases, adult-onset
      Still's disease was diagnosed in all three patients on the basis of clinical and
      laboratory criteria. Adult-onset Still's disease is an important but less well
      known cause of fever. Clinically, adult-onset Still's disease is characterized by
      the triad of fever, skin rash and arthritis/arthralgia. A greatly elevated serum
      ferritin level proved to be an additional valuable diagnostic clue. Treatment
      consists of non-steroidal anti-inflammatory drugs, corticosteroids or
      immunosuppressive agents. The long-term prognosis is usually good, but severe
      joint destruction may occur. All three patients recovered.

PMID- 10923152
TI  - [Deep venous thrombosis of the arm: cause, diagnosis and treatment].

PMID- 10923153
TI  - [Delirium? Admission to the general hospital, rather than the psychiatric
      hospital].

PMID- 10923154
TI  - [Multitrauma patients: principles of 'damage control surgery'].
AB  - The principles of damage control surgery were applied in the cases of three
      severely injured multitrauma patients, men aged 47 and 33 years who had a
      motorcycle accident and a 66-year-old man who had a car crash. Victims of major
      trauma suffer from a worsening physiologic derangement manifested by the triad of
      acidosis, hypothermia and coagulopathy. This often leads to a vicious cycle that
      heralds imminent death or organ failure. Damage control surgery involves three
      distinct stages. The first consists of rapid temporary measures to control
      bleeding and contamination, followed by rapid closure of the abdomen. The second
      involves aggressive correction of the lethal triad in the intensive care unit.
      The third is the planned re-operation for the definitive repair of the injuries.
      As shown in these three patients, the appropriate use of this strategy can lead
      to a decrease in the morbidity and mortality in complex trauma patients.

PMID- 10923155
TI  - [Immunology in medical practice. XXIX. Pathogenesis of allergic and immunologic
      pulmonary diseases].
AB  - Recently acquired insights into the complex functions of the immune system in the
      airways and lungs shed new light on the importance of local immunologic defence
      mechanisms in the maintenance of a normal lung function. Prolonged exposure to
      inhaled allergens or to aspecific injurious substances in the environment, in
      particular, may give rise to the onset of immunopathology that may manifest
      itself only years later. Clinically, the most common of such diseases is allergic
      asthma. This results from the interaction of an unknown number of genes with
      specific and aspecific environmental factors. In chronic obstructive pulmonary
      disease, exposure to such aspecific factors (cigarette smoking) is the most
      important aetiological factor. Immune-mediated diseases may also develop in the
      presence of congenital or acquired immunodeficiencies and in idiopathic diffuse
      pulmonary disorders. In addition, pulmonary disease is often a component of
      collagen diseases, occupational diseases and idiopathic pulmonary fibrosis.
      Recently developed investigational techniques such as bronchoalveolar lavage
      (BAL), cloning experiments on cells obtained by BAL, and ex vivo studies on
      cytokine production patterns are making an important contribution to the acquired
      understanding of the immunopathogenesis of pulmonary diseases.

PMID- 10923156
TI  - [Apoptosis as a focal point for prognostic and therapeutic interventions in
      clinical medicine].
AB  - Apoptosis, physiological cell death, has a major role in the pathogenesis of many
      diseases, notably malignancies, degenerative conditions and diseases of aging.
      Present knowledge about the mechanisms of apoptosis facilitates development of
      biologically targeted drugs directed at specific aberrations in the diseased
      tissues. Clinical medicine is to test the therapeutic potential of these
      substance. Drugs currently under development are targeted at regulators of
      apoptosis, signal transduction, growth factors and growth factor receptors. This
      involves gene therapy and the application of antisense DNA fragments. Recent
      results in biologically anticancer therapy are promising and leave space for more
      intensive tumour eradication by combining with traditional cytotoxic therapy. It
      is to be expected that the years to come will see the development of a biological
      approach to the treatment of degenerative diseases by inhibition of apoptosis.

PMID- 10923157
TI  - [Prevalence of sexually transmitted diseases (STD) and HIV-infection among
      attendees of STD Outpatient Clinic, Dijkzigt University Hospital in Rotterdam;
      comparative analysis of years 1993 and 1998].
AB  - OBJECTIVE: To gain an impression as to the possible trends in the prevalence of
      VD and HIV between 1993 and 1998. DESIGN: Retrospective. METHOD: Data of age,
      gender, ethnic background, sexual preference, intravenous drug use and a
      diagnosis of VD or HIV infection for persons attending the VD Outpatient Clinic
      of the Department of Dermato-Venereology of the Dijkzigt University Hospital in
      Rotterdam, the Netherlands, for the first time were compared for the years 1993
      and 1998. RESULTS: The number of patients examined was 3099 (1894 men and 1205
      women) in 1993 and 3696 (1878 men and 1818 women) in 1998. No diagnosis of
      venereal disease was made in 58.9% and 56.2% of them, respectively. The
      prevalence of HIV infection decreased from 1.3% in 1993 to 0.6% in 1998. This was
      caused mainly by a decline in the prevalence of HIV-antibodies among men with
      homosexual contacts. In the total population, the prevalence of Neisseria
      gonorrhoeae and Chlamydia trachomatis decreased significantly (from 5.4% to 2.5%
      and from 9.3% to 7.5%, respectively), but there was no similar decrease among the
      men with homosexual contacts.

PMID- 10923158
TI  - [Diagnosis and treatment of 39 patients with cervical lymph node metastases of
      squamous cell carcinoma of unknown primary origin, referred to Netherlands Cancer
      Institute/Antoni van Leeuwenhoek Hospital, 1979-98].
AB  - OBJECTIVE: Evaluation of diagnostic procedures and treatment results in patients
      with lymph node metastases of squamous cell carcinoma in the head and neck region
      with an unknown primary. DESIGN: Retrospective, descriptive. PATIENTS AND
      METHODS: In 1979-98, 39 patients (30 male, 9 female; mean age 59 years; range: 39
      88) were treated for cervical lymph node metastases of squamous cell carcinoma
      with an unknown primary. According to protocol, all patients underwent ENT
      examination, radiodiagnostic procedures and, if possible, examination under
      general anaesthesia of the upper respiratory and digestive tracts. Most patients
      were treated by neck dissection followed by bilateral radiotherapy to the neck
      and to mucosal sites of suspected origin. The data were collected from medical
      records. The number of patients who had had no local or regional recurrence and
      were still alive after 5 years were calculated by the Kaplan-Meier method.
      RESULTS: There was a median interval of three months (3-100 weeks) between the
      first symptoms and presentation in our clinic. During this period an extensive
      search for a primary tumour was performed. Most lymph nodes metastases (37/44;
      84%) were found at level II and III. The N-stage was as follows: N1 (6), N2 (14),
      N3 (19). In two patients a primary tumour was diagnosed 20 and 37 months after
      treatment, respectively, both at mucosal sites which were not irradiated. A five
      year locoregional recurrence-free interval was seen in 66%. The five-year overall
      survival rate was 52% and was significantly related to the extent of the cervical
      lymph node metastases. CONCLUSION: Early treatment of patients with cervical
      lymph node metastases from an unknown primary tumour improves survival rates.
      Radiation therapy of the laryngo-pharyngeal axis seems effective in preventing
      outgrowth of an occult primary.

PMID- 10923159
TI  - [Catheter fracture and embolization: a rare complication of a permanent implanted
      intravenous catheter system].
AB  - An implantable venous access system was used in a 55-year-old woman with
      metastatic breast cancer for the delivery of chemotherapy. Four months after
      implantation the catheter was resistant to the injection of fluids. A chest X-ray
      showed fracture of the catheter with embolisation to the right pulmonary artery.
      Analysis of the fractured catheter after removal showed that the fracture was
      caused by catheter pinch-off. Catheter pinch-off is caused by friction of the
      catheter between the clavicle and the first rib. The incidence of this rare
      complication is estimated at 0.1-1%. The incidence of catheter pinch-off can be
      reduced by a lateral insertion technique and by radiographic monitoring after
      implantation.

PMID- 10923160
TI  - [Truth after death; autopsies as an important indicator for quality control].

PMID- 10923161
TI  - [Clinical thinking and decision making in practice. A student with a sudden
      headache].

PMID- 10923162
TI  - [Von Hippel-Lindau disease].

PMID- 10923163
TI  - [Von Hippel-Lindau disease].

PMID- 10923164
TI  - [Von Hippel-Lindau disease].

PMID- 10923165
TI  - [Screening of hearing in children up to 18 months of age].

PMID- 10923166
TI  - [Clinical problems with induction of euthanasia and assisted suicide].

PMID- 10923167
TI  - [Serotonin, 5-hydroxyindolylacetic acid and cholesterol content in blood,
      cerebrospinal fluid and brain areas for differentiation of suicidal from non
      suicidal cause of death].
AB  - In the present study serotonin and its metabolite 5-hydroxyindoleacetic acid was
      investigated in the cerebrospinal fluid and in discrete brain areas of the left
      and right hemisphere collected from 34 bodies. Sixteen subjects were suicide
      victims, and 18 were matched as controls. Matching was done for gender, age, sex
      and cause of death. In suicide victims the concentration of 5-hydroxyindoleacetic
      acid in cerebrospinal fluid (occipital) was significantly decreased whereas there
      was no difference comparing the particular results established from the various
      brain areas. Nevertheless, there was a non-significant trend towards a higher
      concentration of serotonin in the thalamic area and towards a lower level in
      samples collected from the mesencephalon in suicide brains. In suicide subjects,
      the level of 5-hydroxyindoleacetic acid was often found to be increased in the
      hippocampus and to be decreased in the thalamus. A differentiation between
      suicide and homicide seems promising only on condition that the distribution of
      serotonin and metabolite concentrations in various brain areas is considered. The
      amount of total cholesterol in blood is suggested to be of limited value.

PMID- 10923168
TI  - [Forensic medicine experiences in cremation autopsy in Bonn].
AB  - 2016 coroner's crematorial inquests of the Bonn Institute of Legal Medicine over
      a 3 years' period were evaluated and the statements in the death certificates
      were compared to those ones of the Statistical Country Office of Northrhine
      Westphalia. No significant differences were found with respect to age, gender and
      reason of death. However, the number of insufficiently classified deaths with
      respect to the reason of death were overrepresented especially in cases of older
      women, while the number of unnatural deaths was generally underrepresented.
      According to legal medical criteria 2 1/4 per cent of the deaths were falsely
      classified as natural. Only in 2 cases an autopsy was accomplished. Other
      author's statements on the validity of death certificates were confirmed.

PMID- 10923169
TI  - [Self-impalement after thoracic stab wound. An unusual method of suicide in
      psychotic symptomatology].
AB  - A 35 year-old male was found dead within a vast collection of garbage in his
      parent's house with 13 stab wounds of the thorax. 6 years before death he had
      suffered from a severe cerebral trauma with intracranial hemorrhage, after which
      an organic psychosis had ensued. At autopsy besides the stab wounds measuring 1
      3.5 cm in length and partly exhibiting a so-called "fish-tail" formation a piece
      of wood was detected, having penetrated the fourth intercostal space along the
      sternal border and lacerated the pericardium, right pulmonary hilum and the
      pleura parietalis at the paravertebral line between the eight and ninth rib.
      There the leading part of the tool had apparently broken and bent to the left in
      a nearly 90 degrees angle, thus penetrating the left pleural cavity with a slight
      laceration of the lower lobe of the lung. From the forensic pathologist's point
      of view this case of multiple stabbing and additional impalement was at least
      remarkable and at first sight might have raised a suspicion of homicide due to
      the extent of the rib penetrations and especially the intrusion of the wooden
      device, which had been pushed by substantial force into an already existing
      wound. The police presupposed a suicide based on the personal history and
      situation at the site, where no traces suggesting an activity of somebody else
      could be ascertained. Reconstruction of the case and resulting differential
      diagnostic considerations are to be discussed.

PMID- 10923170
TI  - [Suicide by double bolt gunshot wound to the head: case report and review of the
      literature].
AB  - Suicidal gunshot wounds from a livestock stunner with infliction of two shots
      against the head are extremely rare events. A case with these characteristics is
      presented and the corresponding literature is reviewed. A 61-year-old butcher was
      found dead with two entry wounds of the forehead on the right side and in the
      centre being typical for captive bolt pistols (symmetrically localized powder
      burns). The issues of the sequence of shots and the capacity of action are
      discussed on the basis of morphological findings and pathophysiological
      considerations. A literature review revealed only 4 case reports with double
      gunshot wounds of the skull caused by "humane killers" (Tovo 1956, Wolff and
      Laufer 1965, Schiermeyer 1973, Pollak 1977).

PMID- 10923171
TI  - [Case report of accidental stab wound to the heart].
AB  - A 33 year-old Polish field-worker was found by his colleagues kneeling in front
      of his trailer, with a bloody stab wound in the heart region. In spite of prompt
      surgical intervention, the man died from his injury a few hours later. Upon
      examination of the dead man's trailer a blood-smeared vegetable-knife was found
      in the sink, and on the floor, a pullover with a slit-like cut. On the wall hung
      a jacket on a hook with a cut in the inner surface of the left breast pocket but
      not in the outside layer. The examination of the clothes, the autopsy and a
      reconstruction of the sequence of events led to the following conclusion: The
      knife had been placed into the breast pocket of the jacket with the tip facing
      downwards. As the man put down a sack of potatoes, the knife hooked into a pre
      existing gap in the sack and was driven into the chest cavity by the pressure
      weight of the heavy sack.

PMID- 10923173
TI  - Be warned: develop a policy on expired drugs.

PMID- 10923172
TI  - [DNA contamination by examination instruments].
AB  - Using DNA-analysis systems in forensic examination, conditions without any
      (iatrogenic) contamination are necessary for analysis of evidence. Failing these
      conditions a contamination is possible and interpretation of the results may be
      difficult. Our experiments demonstrated a relevant transfer of DNA-material if
      contaminated instruments were used.

PMID- 10923174
TI  - Foot & mouth: spread a major Asian problem.

PMID- 10923175
TI  - Feline inductive odontogenic tumour in a Burmese cat.
AB  - A 7-month-old, male, Burmese cat was presented with an oral mass that had rapidly
      regrown following excisional biopsy 3 weeks earlier. The tumour was identified by
      histological examination as a feline inductive odontogenic tumour. A unilateral
      segmental mandibulectomy was performed. Although dental malocclusion resulted
      from mandibular drift to the operated side, the cat displayed minimal dysphagia
      post-operatively and there was no evidence of tumour regrowth 8 months after
      surgery. Feline inductive odontogenic tumour is a rare dental tumour described
      exclusively in cats under 3-years-of-age. Although histopathologically benign,
      feline inductive odontogenic tumour grows by expansion and can infiltrate
      underlying bone to cause considerable local destruction. This article is intended
      to increase awareness of this unusual tumour which, with complete surgical
      excision, carries a good prognosis. It also emphasises the importance of
      obtaining a histological diagnosis from oral mass lesions to direct appropriate
      therapy and to provide an accurate prognosis.

PMID- 10923176
TI  - Haematological and biochemical findings in cats in Australia with lymphosarcoma.
AB  - OBJECTIVE: To describe, for the first time, haematological and serum biochemical
      findings in cases of lymphosarcoma in Australian cats. DESIGN: A prospective
      multi-institutional study. PROCEDURE: Of 118 affected cats presented to the
      authors over a 18-month period, 97 were evaluated haematologically and 87
      biochemically. Haematological analysis usually included determination of packed
      cell volume, haemoglobin concentration, red blood cell and leukocyte counts,
      differential leukcocyte count, reticulocyte count and examination of buffycoat
      smears for neoplastic cells. Serum biochemical analysis was done primarily with a
      discrete analyser and included a panel of commonly used analytes. RESULTS:
      Nonregenerative anaemia was present in 54% (52/97) of cats. Neutrophilia, present
      in 65% (59/91) of cats, was commonly associated with lymphocytopaenia,
      eosinopaenia and monocytosis. Of the 13 cats with a secondary leukaemic
      manifestation, only five had distinct lymphocytosis. Serum biochemical
      abnormalities either were nonspecific, such as hypoglycaemia in 37% (32/87) of
      cats, or related to specific tissue involvement, such as hypoalbuminaemia in 76%
      (31/41) of cats with alimentary involvement and azotaemia in 60% (15/25) of cats
      with renal involvement. CONCLUSION: It was shown for the first time that
      haematological and serum biochemical findings are of limited value in diagnosing
      lymphosarcoma in Australian cats, except if they are leukaemic. Although clinical
      pathological changes were common, they were nonspecific or related to specific
      tissue involvement. Their value in assessing response to therapy needs to be
      examined further. Patient characteristics such as age, breed and sex also had
      limited effect on laboratory findings and those observed were of little
      consequence. Additionally, histological and immunophenotypical variations in
      tumour type had little effect on laboratory findings.

PMID- 10923177
TI  - Feline hyperthyroidism: spectrum of clinical presentions and response to
      carbimazole therapy.
AB  - OBJECTIVE: To determine the spectrum of clinical presentations of hyperthyroidism
      in cats and response to carbimazole therapy by analysis of historical, clinical
      and laboratory data. DESIGN: A prospective clinical study involving client-owned
      cats presenting to a private veterinary practice in Australia. PROCEDURE: Twenty
      five cats diagnosed as hyperthyroid during a 23-month period participated in the
      study with owner consent. Therapy with carbimazole was instituted and revisits
      were scheduled 2, 6 and 13 weeks after diagnosis. The cats were physically
      examined and underwent haematological and serum biochemical testing at each
      revisit. Owners were also asked to assess clinical signs in their cats in the
      periods between veterinary examinations. Cats with underlying renal disease were
      managed by alterations or cessation of carbimazole therapy. RESULTS: A high
      prevalence of lethargic or inappetent cats without detectable underlying
      nonthyroidal illness was found. There was also a high prevalence of cats less
      than 10-years-old and cats in good body condition. Fourteen cats treated with
      carbimazole and monitored for 13 weeks responded favourably to therapy. Side
      effects were minor and uncommon. Cats with underlying renal disease that became
      apparent during the study, responded well to alterations or cessation of
      carbimazole therapy. CONCLUSION: The trend towards more subtle clinical
      presentations of hyperthyroid cats reported previously continued in this study.
      The findings of the current study do not appear to support the traditional view
      of hyperthyroid cats as being old, hyperactive, hungry and thin. Carbimazole
      therapy was found to decrease the prevalence of almost all clinical abnormalities
      in 14 cats and side-effects were minor and uncommon. This study demonstrates the
      usefulness of medical management of hyperthyroidism in the cat when radioiodine
      therapy is not possible due to renal compromise or other factors.

PMID- 10923178
TI  - Improving the predictability of performance by prerace detection of dorsal
      metacarpal disease in thoroughbred racehorses.
AB  - OBJECTIVE: To determine the prevalence of dorsal metacarpal disease in 2-year-old
      Thoroughbred horses by prerace inspection and to evaluate the effectiveness of a
      dorsal metacarpal disease detection program on the predictability of race
      performance (finishing in the order predicted by punters) and the distance
      between the first- and last-placed horse in a field. DESIGN: A retrospective
      study using client-owned horses. METHODS: A program of prerace detection of
      dorsal metacarpal disease using digital palpation of the dorsal aspect of the
      third metacarpal bone of both forelimbs of 2-year-old Thoroughbreds racing at
      Ascot racecourse was instituted by the Western Australian Turf Club in December
      1995. Horses that had significant pain reaction to digital palpation were
      considered to have pain due to dorsal metacarpal disease, withdrawn from that
      day's race and not permitted to race for 6 weeks. The race records of all 2-year
      old Thoroughbreds racing at Ascot racecourse from December 1993 until December
      1995 were compared with the race results from December 1995 until March 1997,
      after initiation of the dorsal metacarpal disease detection program. RESULTS:
      After initiation of the program, horses were racing more predictably over 1100 m
      (P = 2.09) and 1200 m (P = 3.48). These horses finished closer to the winner over
      1100 m (P = 3.39) and over 1200 m (P = 3.13). In 1000 m races, the trend for
      horses to race more predictably (P = 1.07) and for there to be less distance
      between first and last (P = 1.72) was not statistically significant. CONCLUSIONS:
      The program of prerace digital palpation for dorsal metacarpal disease was
      considered to be beneficial in 2-year-old Thoroughbreds racing over 1100 m and
      1200 m, in that they raced more predictably.

PMID- 10923179
TI  - Subcutaneous larval Taenia serialis in a ring-tailed possum (Pseudocheirus
      peregrinus).
AB  - Coenuriasis is a condition resulting in subcutaneous cyst formation associated
      with infection by the larval stage of Taenia serialis, a tapeworm of the dog and
      associated carnivores. This article is the first report of coenuriasis in an
      Australian arboreal marsupial (I Beveridge personal communication) and only the
      second in an Australian marsupial.

PMID- 10923181
TI  - Aujeszky's disease eradication in New Zealand.

PMID- 10923180
TI  - Temporary importation of Babesia and Ehrlichia seropositive horses into
      Australia.

PMID- 10923182
TI  - Effect of the microclimate on horses during international air transportation in
      an enclosed container.
AB  - OBJECTIVE: To determine if the microclimate is detrimental to horses during
      international air transportation in an enclosed container. PROCEDURE: On each of
      two 12 h and two 24 h flights three horses were transported in an enclosed
      container designed to prevent exposure to insect vectors. Heart rates were
      monitored throughout and blood samples were collected periodically. Air in the
      container was sampled for bacteria and fungal spores and the temperature and
      relative humidity were recorded inside and outside the container periodically
      during the flight. On the two 12 h flights similar observations were made on
      three horses transported in regular open containers, which were used as controls.
      RESULTS: Heart rates during the flights reflected any agitation of the horses.
      Agitation was only mild and generally associated with take-off and landing. There
      were no changes in haematological or blood biochemical values that suggested any
      detrimental effects of the flights. The temperature in the Airstable was
      relatively constant during each flight (means ranged from 18.7 to 23.4 degrees C)
      and was significantly warmer than in the cargo hold (range 13.9 to 18.3 degrees
      C). Relative humidity fluctuated more widely and reflected the ambient humidity
      during airport stops. The numbers of bacteria and fungal spores in the Airstable
      air varied during the flights but were of no apparent significance to the horses'
      health. CONCLUSION: The Airstable proved a convenient means to transport horses
      on international flights and caused no discernible ill effects on the horses
      studied.

PMID- 10923183
TI  - Origins of animal quarantine in Australia.

PMID- 10923184
TI  - Sunlight associated hyperthermia as a consistent and rapidly developing clinical
      sign in sheep intoxicated by St John's wort (Hypericum perforatum).
AB  - OBJECTIVE: To assess the usefulness of rectal temperature responses in Australian
      bred Merino sheep, following the oral administration of Hypericum perforatum (St
      John's wort), as an early indicator of Hypericum intolerance. DESIGN: Thirty
      three Merino ewes were divided into three groups of 11. Each group was dosed with
      finely ground, dried, flowering growth stage H perforatum plant material at
      either 5.7, 4.0, or 2.85 g dry plant per kg live weight. This corresponded to
      5.3, 3.7 and 2.65 mg hypericin per kg live weight, respectively. PROCEDURE: The
      sheep were dosed with a plant slurry by stomach tube and then exposed to bright
      sunlight for up to 5 h per day over successive days. Their clinical responses
      were observed and rectal temperature measured. RESULTS: Ingestion of H perforatum
      followed by exposure to bright sunlight frequently resulted in clinical signs
      attributable to skin irritation and central nervous effects, including an
      inappropriate increase in body temperature. A decrease in H perforatum ingestion
      from 5.7 to 2.85 g dry plant per kg live weight and a corresponding decrease in
      hypericin ingestion from 5.3 to 2.65 mg per kg live weight, was associated with a
      decrease in the severity of the clinical signs, including the severity of the
      hyperthermia. CONCLUSIONS: The rectal temperature rise in affected sheep is a
      reliable indicator of the early development of an adverse clinical effect. There
      appears to be an absolute requirement for exposure to bright sunlight before any
      effects of H perforatum will develop. A single dose of H perforatum remains
      potentially effective for up to 4 days. In the small group of Merino sheep tested
      a tolerance level for H perforatum, eaten at the flowering stage, of < 1% (plant
      wet weight) of body weight and a tolerance level for hypericin of < 2.65 mg per
      kg live weight, were demonstrated.

PMID- 10923185
TI  - Agricultural consultancy--a career choice for veterinarians.
AB  - OBJECTIVE: To document the personal, educational and professional skills that
      characterise veterinarians pursuing careers as agricultural consultants and to
      determine the future direction for veterinary-related advisory services to
      agriculture in Australia. DESIGN: Thirty-six veterinarians practising as
      consultants in agriculture throughout Australia were sent a postal survey in
      1994. PROCEDURE: A descriptive analysis was chosen because of the relatively
      small population available to sample. Comparisons were made on a percentage basis
      where appropriate. RESULTS: Twenty-four useable responses to the questionnaire
      were received. Consultants were mostly men with an agricultural background, aged
      31 to 40 years. They considered their undergraduate veterinary studies to be a
      stepping stone into further education and practical experience and ultimately
      consultancy. Consultants predicted an increased reliance for their work on
      corporate farms, private agribusiness, research and development and sub
      contracted work, rather than on family-owned farms. Consultants disagreed on the
      wisdom of combining consultancy activities with alternative businesses (for
      instance mixed veterinary practice). Only 13 consultants derived greater than 76%
      of their income from consultancy and 14 combined another business with
      consulting. The need for continuing education was considered important.
      Consultants predicted various future prospects for the industry. Many predicted
      that there would not be enough veterinarians to fulfill the demand for this type
      of work. IMPLICATIONS FOR THE VETERINARY PROFESSION: Results from this survey
      suggest that veterinary consulting will extend into finance, agronomy and
      marketing in addition to current skills in animal nutrition, parasite control and
      animal reproduction. As clients demand specialised skills and knowledge, the
      formation of co-operatives or companies of specialists may be beneficial to both
      client and consultant in the future. The consultant's role can be characterised
      as one of extending relevant information to clients in a useful form. Excellent
      communication skills are necessary, as is an understanding of rural issues and
      animal industries.

PMID- 10923186
TI  - Surveillance for aquabirnavirus in fish hatcheries in Victoria.
AB  - OBJECTIVE: To determine whether or not aquabirnavirus is present in Victorian
      fish hatcheries. PROCEDURE: Milt and ovarian fluids were collected from brood
      stock at 12 hatcheries and cultured in two sensitive cell lines for the presence
      of viruses. RESULTS: No cytopathic effect was detected indicating the absence of
      virus. CONCLUSION: There is no evidence of infection with aquabirnavirus or
      Epizootic Haematopoietic Necrosis virus in Victorian fish hatcheries.

PMID- 10923187
TI  - [Hydrolysis of primary amide groups in Asn/Gln-containing peptides].
AB  - Peptides Boc-Ala-Asn/Gln-OH and Boc-Asn/Gln-Ala-OH were saponified with barium
      hydroxide to corresponding Asp/Glu-containing peptides. Under the conditions of
      saponification, Boc-Asn-Ala-OH additionally afforded Boc-Asp-OH, isopeptide Boc
      Asp(Ala)-OH, and Boc-NHSuc > Ala-OH, with the third being the key intermediate in
      these transformations. Boc-Asp(OMe)-Ala-OMe underwent similar transformations
      under treatment with diazomethane or triethylamine. Saponification with barium
      hydroxide was accompanied by a high epimerization of N-terminal amino acid
      residues, whereas the products of the diazomethane treatment of Boc-Asp(OMe)-Ala
      OMe had a low degree of epimerization.

PMID- 10923188
TI  - [Segmented condensation of peptides on a solid phase using subtilisin complexed
      with sodium dodecyl sulfate].
AB  - The subtilisin-sodium dodecyl sulfate complex was shown to catalyze the coupling
      of peptide segments on a solid phase in organic medium. By a two-stage enzymic
      condensation of peptide fragments on aminosilochrom (A) containing Met-Ala-Gly as
      a spacer, Dnp(or Boc)-Ala-Ala-Leu-Ala-Ala-Glu(OMe)-Met-Ala-Gly-A and Z-Ala-Ala
      Glu(OMe)-Ala-Ala-Leu-Met-Ala-Gly-A were obtained. It was shown that the
      condensation products can be split off from the support using the Met residue
      cleavage by BrCN.

PMID- 10923189
TI  - [Localization of disulfide bonds in the alpha 1 acidic glycoprotein molecule and
      study of their effect on ability of the protein to interact with ethidium
      bromide].
AB  - alpha 1-Acid glycoprotein (orosomucoid) was purified from the human and murine
      blood sera using phenol deproteinization. As opposed to the murine protein, the
      human orosomucoid bound the fluorescent dye ethidium bromide but lost this
      ability after treatment with beta-mercaptoethanol, which breaks disulfide bonds.
      Disulfide bonds between the Cys23 and Cys165 residues of the human orosomucoid
      and between the Cys91 and Cys184 residues of the murine orosomucoid were
      identified.

PMID- 10923190
TI  - [Design of the human tumor-associated VNTR(Muc1) antigen gene, fused with
      streptavidin, its expression in Escherichia coli. Study of properties of the
      hybrid protein].
AB  - A gene of human tumor-associated antigen VNTR(MUC1) bound to streptavidin, an
      expression plasmid, and a highly effective hybrid protein-producing strain were
      constructed. It was shown that the streptavidin leader peptide ensures an
      effective secretion of the hybrid protein into the periplasmic space of
      Escherichia coli cells. The hybrid protein was isolated in a homogeneous state
      and its immunogenic properties were studied.

PMID- 10923192
TI  - [A rapid method for testing the activity of the repair enzyme uracil-DNA
      glycosylase].
AB  - A rapid and effective method of testing of a repair enzyme, uracil-DNA
      glycosylase, was proposed. As a substrate, a deoxyuridine-containing 5'-32P
      labeled deoxyoligonucleotide covalently attached to a polystyrene support (Tenta
      Gel S-NH2) was used. The ammonia cleavage of the apyrimidine site formed in the
      enzymic reaction followed by the transition of the labeled oligonucleotide
      fragment from the solid phase into solution allowed the detection of the enzymic
      activity.

PMID- 10923191
TI  - [Deletion mutants of the natriuretic peptide receptor type B: expression of cDNA,
      purification and characteristics of proteins].
AB  - The C type natriuretic peptide (CNP) is a peptide hormone stimulating
      vasorelaxation and inhibiting cell proliferation. CNP activates the type B
      natriuretic peptide receptor (NPR-B), known as the guanylate cyclase B membrane
      enzyme, which results in the cGMP release. To study functional properties of NPR
      B, its gene fragments were expressed in methylotrophic yeasts Pichia pastoris.
      Conditions were found providing for secretion of functionally active recombinant
      proteins NPR-Bs and NPR-B1 into the cultural medium in a yield of 25 mg/ml
      culture. Their specific activity was 0.97 and 0.93 mumol cGMP min-1 mg-1 protein,
      respectively. It was shown that NPR-B belongs to the family of Ser/Thr protein
      kinases and can be autophosphorylated at the serine residues.

PMID- 10923193
TI  - [Determination of substrate specificity of fucosyltransferase from rat brain
      using synthetic acceptors].
AB  - The substrate specificity of fucosyltransferase (FT) from rat forebrain and
      cerebellum was studied using synthetic acceptors. Of 16 acceptors tested, only
      those containing the Gal beta 1-4GlcNAc beta 1-R fragment were subjected to
      enzymic fucosylation. The isomer with a 1-3 bond as well as lactose and
      oligosaccharides with an additional Neu5Ac residue attached to Gal or a Fuc
      residue attached to GlcNAc were not fucosylated whereas Fuc alpha 1-2Gal beta 1
      4GlcNAc displayed the same substrate properties as Gal beta 1-4GlcNAc. FT from
      cerebellum and forebrain was shown to have the specificity similar to that of
      mammalian FT IV. The activity of the cerebellum FT with all types of substrates
      was higher than that of FT isolated from forebrain, the specificity profiles
      being similar.

PMID- 10923194
TI  - [S,X-acetals in nucleoside chemistry. II. Synthesis 3'-O-methylthiomethyl
      derivatives of ribonucleosides].
AB  - 3'-O-Methylthiomethyl derivatives of ribonucleosides were synthesized from the
      selectively protected nucleosides by the action of a dimethyl sulfide-benzoyl
      peroxide mixture in acetonitrile or a dimethyl sulfoxide-acetic anhydride-acetic
      acid mixture.

PMID- 10923195
TI  - [1,6-anhydro-N-acetyl-beta-D-glucosamines in synthesis of oligosaccharides. I.
      Synthesis of 3-acetate and 3-benzoate of 1,6-anhydro-N-acetyl-beta-D-glucosamine
      through a 4-O-trityl derivative].
AB  - 3-O-Acetyl and 3-O-benzoyl derivatives of 1,6-anhydro-N-acetyl-beta-D-glucosamine
      were synthesized via its selective tritylation followed by the 3-O-acylation and
      removal of the trityl protective group. Tritylium trifluoromethanesulfonate,
      which can easily be prepared by mixing solutions of triphenylcarbinol and
      trimethylsilyl trifluoromethanesulfonate in an equimolar ratio, was suggested as
      a reagent for the effective tritylation of a secondary hydroxyl group.

PMID- 10923196
TI  - [Synthesis and antioxidant activity of azole derivatives of hemin].
AB  - New derivatives of proto- and deuterohemin IX containing tri- and tetrazole rings
      were synthesized and characterized. A pronounced antioxidant activity was found
      for these compounds in the Fe(II)/ascorbate-dependent system of lipid
      peroxidation in murine liver homogenates.

PMID- 10923197
TI  - [Halogenation in a series of metallocomplexes of porphyrin].
AB  - We found that thionyl chloride can chlorinate porphyrin complexes with transient
      metals (Pd, Ni, or Cu) at the free beta- and meso-positions of the porphyrin
      macrocycle. A more prolonged or rigorous treatment also causes the chlorination
      of side alkyl substituents, mainly, methyl groups.

PMID- 10923198
TI  - Real-time detection of epileptiform activity in the EEG: a blinded clinical
      trial.
AB  - The aim of this study was to determine the performance of a PC-based system for
      real-time detection and topographical mapping of epileptiform activity (EA) in
      the EEG during routine clinical recordings. The system incorporates a mimetic
      stage to locate candidate spikes (including sharp-waves) followed by two expert
      system-based stages, which utilize spatial and wide-temporal contextual
      information in deciding whether candidate events are epileptiform or not. The
      data comprised 521 consecutive routine clinical EEG recordings (173 hours).
      Performance was evaluated by comparison with three independent
      electroencephalographers (EEGers-I). A second group of two EEGers (EEGers-II)
      separately interpreted the spike topographical maps and, for EEGs categorized as
      containing only questionable EA by the detection system, reviewed 6 sec segments
      of raw EEG centered on each questionable event. Thirty-eight of the EEGs were
      considered to contain definite EA by at least two of EEGers-I. The false
      detection rate of the system was 0.41 per hour. The system was found to have a
      sensitivity of 76% and a selectivity of 41% for EEGs containing definite EA.
      However, it only missed detection of EA in 5% of the recordings. EEGers-II agreed
      with EEGers-I on the distribution (generalized, lateralized, focal, multifocal)
      of EA in 79% of cases. This is by far the largest clinical evaluation of
      computerized spike detection reported in the literature and the only one to apply
      this in routine clinical recordings. The false detection rate is the lowest ever
      reported, suggesting that this multi-stage rule-based system is a powerful and
      practical tool in clinical electroencephalography and long-term EEG monitoring.

PMID- 10923199
TI  - EEG in the elderly: seizures vs. syncope.
AB  - The EEGs of elderly patients with a definite seizure disorder (161 patients; 302
      EEGs) were compared to patients with "syncope" (122 patients; 133 EEGs),
      especially to determine if the latter patients were sufficiently similar to the
      seizure patients that the syncope could be viewed as a seizure phenomenon. The
      two groups were similar only by the predominance of females in both groups (61
      62%) and otherwise were very different. The seizure group had a higher incidence
      of (1) etiology (83 vs. 39%), (2) epileptiform discharges (93 vs. 49%), with a
      different location, more often parasagittal, and different number often with
      active or very active foci, (3) frontal slow waves, (4) more severe slow wave
      abnormalities, (5) slower background frequencies, that were less well organized
      and developed and (6) abnormal records. The conclusion is that the syncope
      patients as a group are usually not simply seizure patients. Regardless of
      etiology, the patients with "syncope" (33% with cerebrovascular and 21% cardiac
      etiologies) showed nearly a 50% incidence of epileptiform discharges,
      demonstrating a complex interrelationship between cardiac and cerebral
      mechanisms, which are discussed. The conclusion is that epileptiform activity in
      elderly patients with syncope is likely to be mildly epileptogenic, and may
      require additional cardiovascular mechanisms to generate an attack of
      unconsciousness.

PMID- 10923200
TI  - Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a
      patient with neurosyphilis.
AB  - We report a case of Jarisch-Herxheimer reaction in a patient with neurosyphilis,
      which was complicated by nonconvulsive status epilepticus. The EEG features
      suggested a focal seizure onset, although the patient's MRI was normal. JHR is
      common in the treatment of neurosyphilis, but usually produces only transient
      systemic constitutional symptoms. Neurologic deterioration is rare, but can be
      dramatic, as in our patient. NCSE should be considered as an explanation for
      persistent obtundation and transient focal neurologic findings in this setting.

PMID- 10923201
TI  - Topographic quantitative analysis of the intrinsic alpha rhythm in chronic
      obstructive pulmonary disease.
AB  - Twenty-two patients with documented COPD and no other significant illnesses were
      studied to assess the effect of varying degrees of COPD on the intrinsic alpha
      rhythm. The severity of COPD was determined by spirometry with assessment of
      FEV1, FVC, and FEV1/FVC. The alpha frequency for COPD patients was slower than
      that which characterizes age equated normals and averages 1.6 S.D. below
      normative data base mean values (range -0.43 S.D. to -1.85 S.D.). Impairment of
      pulmonary functioning significantly correlated with the degree of alpha frequency
      slowing over the posterior cortical regions, and the slowest alpha frequencies
      occurred in those COPD patients with the lowest FEV1/FVC ratios. Impairment of
      cognitive functioning is thus an important clinical consideration in treatment of
      patients with COPD but may go unrecognized until late in the course of the
      disease.

PMID- 10923202
TI  - EEG hemispheric asymmetry as a predictor and correlate of short-term response to
      clozapine treatment in schizophrenia.
AB  - In search of early neuroleptic response predictors in schizophrenia, functional
      interhemispheric and intrahemispheric asymmetry indices, derived from spectrally
      analyzed resting electroencephalographic (EEG) activity, were examined in 17
      schizophrenic patients prior to open label treatment with the atypical
      neuroleptic clozapine. Compared to EEG asymmetry indices derived from a normative
      data bank, patients exhibited significant interhemispheric (left greater than
      right) and intrahemispheric (anterior greater than posterior) deviations in
      delta, theta, alpha and beta frequency bands. Intrahemispheric indices were
      positively correlated with clinical ratings of positive symptoms and global
      psychopathology. Clozapine-induced improvements in positive and negative symptoms
      and global psychopathology symptom ratings were related to pretreatment
      intrahemispheric asymmetry only, with relationships varying with symptom,
      recording region and frequency band. The results are discussed in relation to the
      neurobiology of schizophrenia and the utility of EEG as an informative predictor
      of treatment response.

PMID- 10923203
TI  - Absence seizures and the frontal lobe.
AB  - There is no doubt that the frontal lobe plays a major role in the 3/sec spike
      wave absence seizure. It is pointed out initially that the controversies of
      cortical vs. thalamic origin of the spike-waves and the associated absence can be
      laid at rest as far as human absence seizures and human primary generalized
      epilepsy (PGE) are concerned: their origin is cortical with maximal frontal lobe
      involvement. Experimentally-induced spike-wave bursts or spontaneous spike-waves
      in animals pertain to other forms of epileptic seizure disorder. The frontal
      maximum of the 3/sec spike-wave pattern indeed indicates maximal frontal lobe
      involvement including both prefrontal and frontomotor portions. The absence as
      such is presumed to be a suspension of the working memory--an eminently frontal
      lobe function. This explains the immediate restoration of ictally-impaired
      neurocognitive functions right at the termination of the seizures. This concept
      can be applied not only to the classical absence occurring in PGE but also to the
      rare cases of secondary bilateral synchrony with a primary frontal epileptogenic
      focus leading to true (though very slightly different) absences.

PMID- 10923204
TI  - Nose wiping: an unrecognized automatism in absence seizures.
AB  - Nose wiping is a well-known postictal automatism in complex partial seizures,
      considered very important for lateralization. We report a 24-year-old woman
      selected from 32 patients with video-EEG investigations of absence seizures. The
      patient, with normal examination and imaging findings, had typical absence
      seizures from the age of 5 years, which were controlled with either ethosuximide
      or valproate and worsened by carbamazepine. In two of her recorded typical
      absence seizures associated with generalized 3 Hz symmetric spike-wave
      discharges, she wiped her nose as an automatism in the ictal and post-ictal
      period. Our case showed that nose wiping could be associated with generalized
      seizures, in contrast to other recent reports.

PMID- 10923205
TI  - Early-latency somatosensory evoked potentials elicited by electrical acupuncture
      after needling acupoint LI-4.
AB  - The stimulating methods of prior studies on somatosensory evoked potentials
      (SEPs) elicited by acupoint stimulus had involved surface electrodes, while the
      clinical practice of acupuncture is mostly performed by inserting the acupuncture
      needle inside the body. Clinical observations show that there are often some
      special sensations when LI-4 is needled. To observe if the SEPs produced by
      acupoint acupuncture had a distinguishing property, we studied the SEPs elicited
      by electrical acupuncture after the acupuncture needle was inserted into LI-4 and
      its control point, and then mapped them with the 128-channel Electric Brain
      Signal Image system. We also compared this to SEPs by median nerve stimuli.
      Results showed that the most interesting finding was the marked differences of N1
      P1 and N2-P2 amplitude between SEPs at LI-4 (SEP-LI) and its control point (SEP
      CP), which were in the opposite direction. Marked differences were also found
      between latencies and amplitudes of the SEPs elicited by acupuncture and by
      median nerve stimulus (SEP-M). The differences between SEP-LI and SEP-CP might be
      due to the additional effects of the activation of nerve endings and muscle
      spindles in LI-4 to the SEPs formed by the activation of superficial and deep
      radial nerves during electrical acupuncture. The differences between SEPs to
      acupoint and median nerve stimuli might be mainly due to the different distances
      from the stimulated regions to the cerebral cortex, the diversity and the number
      of activated fibers.

PMID- 10923206
TI  - 'New' active steroids and an unforeseen mechanism of action.
AB  - Steroid hormones mostly act via nuclear receptors. Dehydroepiandrosterone (DHEA),
      pregnenolone (PREG) and their sulphate(s), classically known only as hormonal
      precursors, are also neurosteroidal efficacious signals, modulating
      neurotransmitter receptor function at the membrane level. An additional
      unforeseen mechanism of steroid action is reported here: PREG binds to neural
      microtubule-associated protein MAP2 and increases both the rate and extent of
      tubulin polymerization studied in vitro with purified tubulin and MAP2, forming
      microtubules of normal electron microscopic appearance. Progesterone and PREGS
      also bind to MAP2, but counteract PREG activity. In cultured neurons, PREG
      specifically increased immunostaining by an antiMAP2 monoclonal antibody and its
      extension into neurites. This novel mechanism may play a role in regulating
      microtubule formation and dynamics, which are altered in brain ageing and
      diseases.

PMID- 10923207
TI  - Molecular basis of epithelial thyroid tumorigenesis.
AB  - The results of experiments carried out in different laboratories (including ours)
      during the last 10 years have enabled us to propose the hypothesis that there are
      different initiators able to start the epithelial thyroid tumorigenic process via
      different pathways:--gsp and TSHR genes: at the origin of hyperfunctioning tumors
      (toxic nodules and adenomas);--ras and probably gsp genes (in a minority of
      samples): via a vesicular adenoma progressing eventually to a vesicular
      carcinoma. This could be also the case for ret but only in radiation-associated
      tumours;--ras, ret, trk and probably gsp and met: starting from small papillary
      lesions ('spontaneous' or radiation-induced) and progressing to a clinically
      evident papillary carcinoma;--the p53 gene playing a role only in the final
      dedifferentiation process. Simultaneous alteration in the same sample of
      combinations of ras, gsp, ret, trk and TSHR was found in only a minority of the
      approximately 150 tumours studied. These data suggest an interchangeable role for
      these genes in the initiation of 'spontaneous' or radiation-associated epithelial
      thyroid tumorigenesis. The requirement of one of the genes cited above to
      interact with other genes must not be neglected. Ras is the most frequently
      altered gene in 'spontaneous' thyroid tumours and ret in radiation-associated
      thyroid tumours.

PMID- 10923208
TI  - In vivo 129Xe NMR in rat brain during intra-arterial injection of hyperpolarized
      129Xe dissolved in a lipid emulsion.
AB  - Hyperpolarized 129Xe was dissolved in a lipid emulsion and administered to
      anaesthetized rats by manual injections into the carotid (approximately 1-1.5 mL
      in a maximum time of 30 s). During injection, 129Xe NMR brain spectra at 2.35 T
      were recorded over 51 s, with a repetition time of 253 ms. Two peaks assigned to
      dissolved 129Xe were observed (the larger at 194 +/- 1 ppm assigned to
      intravascular xenon and the smaller at 199 +/- 1 ppm to xenon dissolved in the
      brain tissue). Their kinetics revealed a rapid intensity increase, followed by a
      plateau (approximately 15 s duration) and then a decrease over 5 s. This
      behaviour was attributed to combined influences of the T1 relaxation of the
      tracer, of radiofrequency sampling, and of the tracer perfusion rate in rat
      brain. Similar kinetics were observed in experiments carried out on a simple
      micro-vessel phantom. An identical experimental set-up was used to acquire a
      series of 2D projection 129Xe images on the phantom and the rat brain.

PMID- 10923209
TI  - [Asymmetry and growth rate of the shell valves in juveniles of Crassostrea gigas
      Thunberg].
AB  - Thanks to a sampling of juvenile oysters with different growth rates (slow,
      medium and fast), a subtle biometrical study of their shell evolution is
      described distinguishing the two valves. We conclude that all the phenomena are
      dominated by the early establishment of a directional asymmetry, which rapidly
      becomes so large that we should consider dissymmetry. The clearest relationship
      is revealed to be that between the weakness of the growth rate and the degree of
      the relative dissymetry between the weights of the valves. This result is to be
      compared with the highly debated relationship between the asymmetry and the
      growth rate. The existence and interpretation of both of these phenomena have led
      to many publications.

PMID- 10923210
TI  - Periosteal bone growth rates in extant ratites (ostriche and emu). Implications
      for assessing growth in dinosaurs.
AB  - The first quantitative experimental data on growth dynamics of the primary
      cortical bone of young ratites demonstrate the following. 1) From hatching to 2
      months of age, cortical thickness remains constant, thereby expressing
      equilibrium between periosteal bone deposition and an endosteal bone resorption.
      2) Radial growth rates of the diaphyseal bone cortex are high (10-40 microns.day
      1 on average--maximum 80 microns.day-1) in the hindlimb (femur, tibiotarsus and
      tarsometatarsus). Wing bones are smaller and later developed. They have lower
      rates of radial osteogenesis (2-14 microns.day-1). 3) High growth rates are
      linked to densely vascularized primary bone belonging to the reticular or laminar
      tissue types. Growth rates fall when bone vascular density decreases. These
      results emphasize the importance of examining a large number of skeletal elements
      in order to build a precise knowledge of the general relationship between bone
      growth rate and bone tissue type. They also stress the potential of bone growth
      rate quantification among extinct tetrapods, including non-avian dinosaurs.

PMID- 10923211
TI  - [Proline accumulation by tomato leaf tissue in response to salinity].
AB  - The capacity of tomato leaf tissues to accumulate proline in response to a salt
      shock (150 mM NaCl) applied to excised shoots, leaves, leaflets or leaf discs was
      determined and compared to that of whole plants grown at the same salinity. The
      associated changes in free amino acids, Na+, K+ and Cl- contents were also
      investigated. In excised organs treated for 80 h, up to 200 mumol g-1 DW of
      proline were accumulated, whereas the amount of proline in leaf discs did not
      exceed a value ten-fold lower. In the whole plants subjected to salinity the Na+,
      Cl- and K+ contents remained low in comparison to that observed in excised
      organs. Proline and other amino acids increased more slowly in whole plants than
      in excised shoots. The contribution of roots and vascular tissues to the control
      of Na+ and Cl- accumulation and to the regulation of proline metabolism are
      discussed.

PMID- 10923212
TI  - Annual fluctuation in amplitudes of daily variations of electrical signals
      measured in the trunk of a standing tree.
AB  - Electrical potential differences between electrodes inserted in eight selected
      sites of the trunk of a Turkey oak (Quercus cerris) and the ground have been
      recorded continuously since November 1997. The mean amplitudes of daily electric
      variations were determined for time intervals when the meteorological and
      atmospheric electricity conditions were undisturbed. It was found that the mean
      daily amplitudes show a characteristic annual fluctuation. Both in 1998 and in
      1999 two peaks were observed: the first maximum appears suddenly about the end of
      March, and the second one was seen in late June, July. Between November and March
      the mean amplitudes were smaller by about one order of magnitude.

PMID- 10923213
TI  - [Effect of hydrodynamics on the prey-predator relation. Experimental approach in
      a hydrodynamic channel].
AB  - Coupling effects of hydrodynamics and predatory activity of Nepthys hombergii
      (Savigny) (Polychaeta: Nephtyidae) on emigration of Hediste diversicolor (O.F.
      Muller) (Polychaeta: Nereidae) recruits were assessed in a flume. Experiments
      carried out in still water conditions and in the flume flow showed that predatory
      activity of N. hombergii is independent of the presence or the absence of flow
      and does not statistically influence the recruit emigration rate. It appears,
      however, that hydrodynamics is an inhibiting factor for the emigration of H.
      diversicolor which occurs in the absence of flow. The comparison of these results
      with literature data suggests that recruits could use hydrodynamics to leave an
      unsuitable habitat according to the species mobility range.

PMID- 10923214
TI  - [Cranial and mandibular morphology of the Indrinae. Contribution of Procrustes
      methods and Fourier analysis].
AB  - Although it is universally accepted that the Indridae family is monophyletic,
      there is no such unanimity about how the extant species of the Indrinae sub
      family are related. Cranium and mandible disparity among Indri indri, Propithecus
      diadema, Propithecus verreauxi and Avahi laniger is analysed by geometrical
      morphometric methods and interpreted in adaptive terms. We compare results
      obtained by two techniques: Procrustes superimpositions for skulls and elliptical
      Fourier analysis for jawbones. In both studies, the three genera are clearly
      isolated. Avahi laniger is the species with the most paedomorphic cranium while
      Indri indri has the most 'juvenile' mandible. Cranial morphology is governed
      principally by orbit volume and body size, while jaw shape is related to diet
      (enlargement of the gonial region).

PMID- 10923215
TI  - [Origin of Ginkgo biloba L. Phylogenetic approach].
AB  - A cladistic analysis on fossil and modern Gymnosperms (20 taxa) is presented and
      discussed with particular mention of Ginkgo biloba L. origin. The consensus tree
      obtained from 68 characters (59 informative characters) shows a monophyletic
      clade containing all plants bearing micropylate ovules ('Micropylophytes').
      Medullosales appear at the base of this clade. Ginkgo forms the sister group of
      the Dicranophyllales + Coniferales. The obtained phylogeny implies that the
      Ginkgoales ancestor is to be found during the Upper Carboniferous.

PMID- 10923216
TI  - Histogenesis control genes and neurofibromatosis 1.

PMID- 10923217
TI  - Multiple coronary artery aneurysms in a child with neurofibromatosis type 1.
AB  - A number of frequently unrecognised vascular manifestations have been described
      in patients with neurofibromatosis type 1 (NF1), including involvement of the
      great vessels, cerebral, visceral and renal arteries. Rarely, changes in the
      coronary arteries have been reported in adults with NF1. We report on a 16-year
      old boy affected by NF1 with dysmorphic features and three aneurysms in the mid
      portion of the left descending coronary artery disclosed by chance during
      investigation for a malignant peripheral nerve sheath tumour. Molecular analysis
      detected a gross de novo deletion in the NF1 gene. The boy had had no previous
      cardiac symptoms but died suddenly after developing signs and symptoms suggestive
      of myocardial infarction. CONCLUSION: To the best of our knowledge, this
      represents the first report of multiple lesions in the coronary arteries in a
      child affected by neurofibromatosis type 1 with a known deletion of the
      neurofibromatosis type 1 gene.

PMID- 10923218
TI  - Hydrops fetalis associated with erythrocyte pyruvate kinase deficiency.
AB  - The authors report a case of hydrops fetalis due to severe pyruvate kinase
      deficiency, the most unusual clinical manifestation of this disease. CONCLUSION:
      Pyruvate kinase deficiency, as other erythrocyte enzymopathies, must be
      considered in the differential diagnosis of non-immune hydrops fetalis. This has
      important implications for clinical investigations, therapy and genetic
      counselling.

PMID- 10923219
TI  - Rapid appearance and onset of action of insulin aspart in paediatric subjects
      with type 1 diabetes.
AB  - The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with
      those of soluble human insulin following subcutaneous administration in nine
      children (aged 6-12 years) and nine adolescents (aged 13-17 years) with stable
      type 1 diabetes. The study had a randomised, double-blind, two-period crossover
      design. Each patient received a single subcutaneous dose of insulin aspart or
      human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma
      insulin and glucose concentrations were measured at intervals during the
      following 5 h. The pharmacokinetic profile of insulin aspart differed
      significantly from that of human insulin with a higher mean maximum serum insulin
      (Cmax ins), 881 +/- 321 (SD) pmol/l versus 422 +/- 193 pmol/l for human insulin
      (P < 0.001); and with a shorter median serum insulin tmax ins, 40.0 min
      (interquartile range: 40-50 min) versus 75.0 min (interquartile range: 60-120
      min) for human insulin, (P < 0.001). An age-related effect on Cmax ins and area
      under the curve (AUC0-5 h ins) was observed with higher values in adolescents
      than in children for both insulin aspart and human insulin. Postprandial
      glycaemic control was improved with insulin aspart; the baseline-adjusted delta
      Cmax glu being lower for insulin aspart compared with human insulin (increase of
      7.6 +/- 5.1 versus 9.4 +/- 4.4 mmol/l respectively, P < 0.05). The incidence of
      adverse events was similar for the two insulin types. CONCLUSION: The more rapid
      onset of action of insulin aspart versus human insulin, previously observed in
      adults, is confirmed in a paediatric population with type 1 diabetes.

PMID- 10923221
TI  - The geographic distribution of cystic fibrosis mutations gives clues about
      population origins.
AB  - Information regarding three of the more common cystic fibrosis mutations is
      presented (delta F508, G542X, N13031K) to support the concept of a geography
      associated with cystic fibrosis mutations. We present the hypothesis that a
      knowledge of the geography of cystic fibrosis mutations is important for an
      understanding of genotype-phenotype correlations, gene flow, historical
      population migration and cystic fibrosis screening. CONCLUSION: A new method of
      study of mankind's cultural spread is being revealed and the survival of the
      various mutations supports the concept that they may provide a selective
      advantage to the carrier.

PMID- 10923220
TI  - Effects of continuing paediatric education in interpersonal communication skills.
AB  - Paediatric care places great demands on interpersonal communication skills,
      especially as regards the handling of psychosocial issues. Recent shifts in
      paediatric morbidity and increases in patient empowerment furthermore emphasize
      the need for continuing paediatric education in communication skills. It is,
      however, debatable, whether after residency paediatric education can influence
      paediatrician performance. This study evaluated the effects of a 5-day
      experiential communication training by means of a pretest/post-test control group
      design. A total of 21 consulting paediatricians (10 experimental, 11 control
      group paediatricians) videotaped two series of consecutive outpatient encounters.
      Compared with the untrained control group, trained paediatricians asked more
      psychosocial questions and looked at the patients and their parents more often.
      In addition, they gave patients and parents more room to talk. No difference was
      found in the length of the outpatient visits. CONCLUSION: Paediatric education
      after residency influences paediatricians' verbal and nonverbal communication
      skills positively, especially as regards handling psychosocial issues. On the
      basis of these findings, it appears worthwhile to encourage continuing paediatric
      education in interpersonal communication skills.

PMID- 10923222
TI  - The hyponatraemic hypertensive syndrome in a 2-year-old child with behavioural
      symptoms.
AB  - In this case report we present a 2-year-old girl with the classical signs of the
      hyponatraemic hypertensive syndrome. She initially presented with a history of
      behavioural abnormalities and hyponatraemia (126 mmol/l) and her blood pressure
      was as high as 220/160 mmHg. After admission, somnolence developed. Intravenous
      anti-hypertensive therapy was started immediately. The hyponatraemia was treated
      with i.v. sodium supplementation. The cause of this syndrome proved to be
      fibromuscular dysplasia of the left renal artery. Finally, a left nephrectomy was
      performed. With this therapy, blood pressure and serum sodium normalised and the
      girl promptly regained normal consciousness and behaviour. CONCLUSION:
      Behavioural abnormalities in the history of a child without any other
      neurological symptoms might be one of the first signs of hypertensive
      encephalopathy. In combination with hyponatraemia, these symptoms should alert
      the physician to consider the hyponatraemic hypertensive syndrome.

PMID- 10923224
TI  - Paediatric Behcet disease manifested as recurrent myositis: from an incomplete to
      a full-blown form.
AB  - A 12-year-old boy presented with a limp and findings suggesting localised
      myositis of his right calf and a working diagnosis of Behcet disease was made.
      During 3 years of follow-up, he had another three episodes of calf myositis, all
      responsive to corticosteroids within days. CONCLUSION: A case of recurrent
      localised myositis as a main manifestation of Behcet disease is reported. The
      evolution of incomplete Behcet disease, which is common in children, to the full
      blown form, with the emphasis on muscle involvement and the importance of early
      diagnosis of Behcet disease, is discussed.

PMID- 10923223
TI  - Cutaneous porphyria in a neonate with tyrosinaemia type 1.
AB  - A term infant born to consanguineous parents presented at birth with
      hypoglycaemia, thrombocytopenia, coagulopathy and hyperbilirubinaemia associated
      with polycythaemia due to delayed cord clamping. Despite phototherapy and
      correction of polycythaemia by partial exchange transfusion, coagulopathy,
      hypoglycaemia and conjugated hyperbilirubinaemia persisted, suggesting hepatic
      failure. Metabolic work-up led to the diagnosis of tyrosinaemia type 1 on day 4.
      Two--(2-nitro-4-trifluoromethylbenzoyl)--1,3 cyclohexanedione (NTBC) treatment,
      started on day 5, resulted in progressive clinical improvement and unambiguous
      biochemical response. Severe skin purpuric lesions occurred in areas exposed to
      phototherapy. These resolved slowly after its discontinuation. Urine analysis
      sampled just before and 6 days after starting NTBC treatment showed high levels
      of type 1 coproporphyrin isomers. Such findings do not seem directly related to
      tyrosinaemia type 1 where succinylacetone inhibits delta-aminolevulinic acid
      (delta-ALA) dehydratase and where the accumulation of delta-ALA results in
      neurotoxicity without photosensitivity. CONCLUSION: We describe a cutaneous form
      of porphyria in a neonate presenting with severe liver failure due to
      tyrosinaemia type 1. This porphyria is tentatively attributed to a secondary
      accumulation of coproporphyrins due to cholestasis, as reported in the bronze
      baby syndrome and recently described in neonates with purpuric phototherapy
      induced eruption, rather than to a primary defect of porphyrin metabolism. The
      hypothesis of a direct effect of tyrosinaemia type 1 on porphyrin excretion is
      also discussed.

PMID- 10923226
TI  - Hearing loss in children with osteogenesis imperfecta.
AB  - Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue.
      Progressive hearing loss is one of the principal symptoms of OI, affecting about
      50% of adult patients. Hearing loss may also occur in childhood and results in
      additional disability in education and psychosocial adaptation and aggravates the
      physical handicap. This can be avoided by appropriate otological and audiological
      treatment. In a nationwide search, 254 Finnish patients with OI were identified
      indicating a prevalence of 4.9/100,000. Of the 60 children, 45 aged between 4 and
      16 years accepting to participate the study on hearing, were evaluated by a
      questionnaire and clinical audiometry. Hearing loss was defined as pure tone
      average (PTA0.5-2 kHz) more than 20 dB hearing level (HL). A clinical geneticist
      determined the type of OI among the 45 patients. Two sporadic OI cases with
      conductive hearing loss were ascertained (4.4%): An 11-year-old girl with type IV
      OI with a PTA0.5-2 kHz of 35/40 dB HL and a 15-year-old boy with type IV OI with
      a PTA0.5-2 kHz of 27/18 dB HL. In addition, a 6-year-old girl with familial OI
      type I had either a congenital sensorineural deafness or early progressive
      deafness with PTA0.5-2 kHz of 97/103 dB HL, probably of unrelated aetiology.
      CONCLUSION: Hearing loss in children with osteogenesis imperfecta is less
      frequent than generally suspected. Nevertheless, it is recommended that
      audiometry is performed in children with osteogenesis imperfecta even without
      symptoms of hearing loss at the age of 10 years, and repeated every 3 years
      thereafter.

PMID- 10923225
TI  - Retrograde holodiastolic flow in the abdominal aorta detected by pulsed Doppler
      echocardiography in patients with Kawasaki disease.
AB  - Retrograde holodiastolic flow in the abdominal aorta (retrograde flow) detected
      by pulsed Doppler echocardiography is usually noted in patients with aortic
      regurgitation or patent ductus arteriosus. Similar abnormal flow often is present
      in patients with acute phase Kawasaki Disease (KD). In 21 patients with acute
      phase KD, 15 had a retrograde flow. Retrograde flow was recognised in only 3 of
      patients with acute infection (n = 31) and in no healthy controls (n = 10). The
      ratio of the time velocity integral for diastolic retrograde flow to that for
      antegrade flow (regurgitant fraction) was significantly greater in patients with
      KD (median value 23%) than in patients with acute infection (1%) or healthy
      individuals (1%) (P < 0.001 for both). Four patients with coronary arterial
      involvement (one with an aneurysm and three with transient dilation of the
      coronary arteries) had a greater regurgitant fraction than the 17 patients
      without coronary arterial involvement (median values: 31% versus 18%, P < 0.05).
      The C-reactive protein was increased for a longer period of time in patients with
      KD with a greater regurgitant fraction (P < 0.01). Plasma nitric oxide (NO)
      metabolite concentrations were significantly greater in patients with KD than in
      those with acute infection or in healthy controls (P < 0.001 for both). There was
      a positive correlation between plasma NO metabolite concentrations and the
      regurgitant fraction in patients with KD (r = 0.69). CONCLUSION: Retrograde flow
      in the abdominal aorta is increased in patients with Kawasaki disease. Further
      studies are needed to clarify the causal relationship between the abnormal flow
      and the overproduction of nitric oxide.

PMID- 10923227
TI  - Scleroderma-like syndrome in a child: eosinophilic fasciitis or scleredema
      adultorum?
AB  - A 6-year-old female patient presented with a rapidly progressive scleroderma-like
      syndrome involving almost the entire integument. Initially clinical patterns and
      histopathological data of both eosinophilic fasciitis and scleredema adultorum
      were present. The course of the disease remained unusual for both conditions but
      finally argued in favour of the diagnosis of eosinophilic fasciitis. CONCLUSION:
      Eosinophilic fasciitis and scleredema adultorum might be subtypes of one disease
      entity.

PMID- 10923228
TI  - End-stage liver disease as the only consequence of a mitochondrial respiratory
      chain deficiency: no contra-indication for liver transplantation.
AB  - The prerequisite for liver transplantation as a therapeutic option for inherited
      metabolic diseases should be that the enzyme defect, being responsible for the
      major clinical (hepatic and/or extra-hepatic) abnormalities, is localised in the
      liver. Furthermore, no adequate dietary or pharmacological treatment should be
      available or such treatment should have an unacceptable influence on the quality
      of life. We report an infant, who developed end-stage liver disease with
      persistent lactic acidaemia in his first months of life. Analysis of the
      mitochondrial respiratory chain in liver tissue revealed a combined partial
      complex I and IV deficiency. No extra-hepatic involvement could be demonstrated
      by careful screening for multiple organ involvement, including analysis of the
      mitochondrial respiratory chain in muscle tissue and cultured skin fibroblasts.
      The boy received a reduced size liver graft at the age of 8 months. He recovered
      successfully. Almost 5 years after transplantation he is in good clinical
      condition. No clinical or biochemical signs of any organ dysfunction have been
      demonstrated. The considerations on which basis it was decided that there was no
      contra-indication to perform liver transplantation in this patient are discussed.
      CONCLUSION: The possibility of a mitochondrial respiratory chain deficiency
      should be considered in liver disease of unknown origin prior to liver
      transplantation. Liver transplantation is a therapeutic option in mitochondrial
      respiratory chain deficiency-based end-stage liver disease provided that extra
      hepatic involvement is carefully excluded.

PMID- 10923229
TI  - Streptococcus pyogenes meningitis: report of a case and review of the literature.
AB  - Streptococcus pyogenes is a very uncommon cause of bacterial meningitis beyond
      the neonatal period. A case report and a review of the recent literature is
      presented. We report on a previously healthy 7-year-old boy who developed S.
      pyogenes meningitis following a 2-day history of otitis media. A CT scan revealed
      right-sided mastoiditis as a possible focus of infection. The patient was treated
      with penicillin G for 14 days. The clinical course was uneventful, and the
      recovered without sequelae. By means of the polymerase chain reaction, the
      presence of streptococcal pyrogenic exotoxin (SPE) B and SPE C, but not SPE A
      genes was discovered from the bacterial DNA. CONCLUSION: Streptococcus pyogenes
      is a rare cause of bacterial meningitis but has to be considered as the causative
      pathogen beyond the neonatal period.

PMID- 10923231
TI  - Tuberculous meningitis in children: problem to be addressed effectively with
      thorough contact tracing.
AB  - Worldwide, tuberculosis is the most common cause of death from a single
      infectious agent in children. There has been an increase in its incidence in
      Europe in recent years. Early diagnosis of tuberculous meningitis in children is
      extremely difficult because of its nonspecific early presentation and it is
      universally fatal if not recognised and treated. Young children are at increased
      risk of acquiring tuberculosis and it is more likely to be disseminated in
      neonates. In summarising the cases of three children with tuberculous meningitis
      admitted to our centre, we highlight the importance of diagnosis and contact
      tracing of the source case. CONCLUSION: Diagnosis of tuberculous meningitis
      requires a high index of suspicion, thorough contact tracing, and appropriate
      investigations with early treatment as the key to reducing morbidity and
      mortality.

PMID- 10923230
TI  - Schistosomiasis in German children.
AB  - Reports on schistosomiasis in children growing up in Europe are rare despite
      increased travel activity. We report on eight male and three female German
      children aged 50 months to 15 years with schistosomiasis. Six children were
      asymptomatic, whereas two presented with typical signs of Katayama fever.
      Persisting haematuria, headache with eosinophilia and pyelonephritis were
      observed in one child each. An exposure was reported for six of the children. Two
      were examined solely because schistosomiasis was diagnosed in a family member.
      All had antibodies against schistosomal antigens in at least two of three
      screening tests. However, schistosomal ova (Schistosoma haematobium) were
      detected in urine and faecal specimens from only three children. A tumour-like
      lesion of the bladder was found by ultrasound in only one of the children who
      also exhibited haematuria. Neither eosinophilia nor elevated IgE levels were
      constant findings. Six to 12 months after praziquantel treatment, parasitological
      and ultrasound checks were negative and levels of specific antibodies decreased.
      However, 2 years later, elevated antibody levels were detected in one girl
      without evidence of any new exposure. She became antibody-negative 1 year after a
      second course of treatment. CONCLUSION: In contrast to residents of endemic
      areas, parasitological and ultrasound examinations seem to be inferior to
      immunodiagnostics in children from non-endemic areas at temporary risk for
      schistosomiasis.

PMID- 10923232
TI  - Suspected sexual abuse: an unusual presentation form of congenital myotonic
      dystrophy.
AB  - In children, anal abnormalities due to various causes may be confused with sexual
      abuse. We present the case of a child in whom the suspicion of abuse due to anal
      dilatation led to the previously unknown diagnosis of myotonic dystrophy.
      Myopathic involvement of the perianal musculature is a known feature of
      congenital myotonic dystrophy that usually appears in late childhood or
      adolescence. CONCLUSION: We stress the importance of considering an underlying
      myopathic condition in the differential diagnosis of anal laxity. Further
      studies, such as anal ultrasonography, may help when the diagnosis of abuse is
      not clear.

PMID- 10923233
TI  - Confounding in the study of pacifier use in sudden infant death syndrome.

PMID- 10923234
TI  - Rickets and myelofibrosis.

PMID- 10923235
TI  - A painful, hot and swollen knee with sterile synovial fluid. Foreign body
      synovitis.

PMID- 10923237
TI  - Cholelithiasis in a newborn following treatment with the somatostatin analogue
      octreotide.
AB  - We report the case of a newborn infant affected by congenital hyperinsulinism who
      developed cholelithiasis associated with cholestatic jaundice following treatment
      with octreotide, a somatostatin analogue.

PMID- 10923236
TI  - Can near infrared spectroscopy of the liver monitor tissue oxygenation?
AB  - Measurement of the hepatic oxygenation index by near infrared spectroscopy is a
      suitable method to estimate the oxygenation and can be a non-invasive means to
      continuously monitor tissue perfusion and to detect early haemodynamic
      disturbances in critically ill children.

PMID- 10923238
TI  - Decreasing early recurrence rate of acute intussusception by the use of
      dexamethasone.
AB  - Premedication with intramuscular dexamethasone may decrease the rate of early
      recurrent intussusception by amelioration of lymphoid hyperplasia.

PMID- 10923239
TI  - Neonatal exchange transfusion with heparinised whole blood or citrated composite
      blood: a prospective study.
AB  - Heparinised blood should be kept as an available option for neonatal exchange
      transfusions.

PMID- 10923240
TI  - Gastric pneumatosis following cardiac surgery.
AB  - Infiltration of the stomach wall by air, first described by Fraenkel in 1889 [3],
      is a very rare condition. We describe the first reported case of gastric
      pneumatosis occurring in a child with complex congenital heart disease after
      cardiac surgery.

PMID- 10923241
TI  - Chloride fluxes during cAMP stimulation of liquid absorption across the native
      rat alveolar epithelium.
AB  - cAMP activates Cl- channels in the alveolar epithelium of rabbits (Nielsen et al.
      Am J Physiol. 1998; 275:L1127-L1133), resulting in Cl- secretion; and of rats
      (Jiang et al. Am J Physiol. 1998; 275:C1610-C1620), resulting in Cl- absorption.
      The relationship between Cl- fluxes and liquid absorption across the alveolar
      barrier was examined using isolated perfused rat lungs. Unidirectional 36Cl-
      fluxes (apparent PACl products) in the apical-to-basal (absorption, PAClab) and
      reverse (secretion, PAClba) directions were identical under control conditions.
      Both increased about 2-fold during stimulation of liquid absorption by
      dibutyrylcAMP + isobutylmethylxanthine (P < .001). Inhibiting Na+ and liquid
      absorption during cAMP stimulation by adding amiloride to the alveolar instillate
      decreased PAClab to control level (P < .01), but did not affect PAClba. Neither
      alveolar liquid absorption nor PAClba was affected by apical N-phenylanthranilic
      acid or basolateral bumetanide during cAMP stimulation. Mannitol permeability-
      surface area products did not differ with the experimental condition. These
      observations indicate that cAMP stimulation results in enhanced Cl- and liquid
      absorption from rat airspaces and Cl- secretion into them. They suggest that Cl-
      absorption follows Na+ transport, but fail to demonstrate any significant
      participation of cAMP-activated Cl- channels in these changes.

PMID- 10923242
TI  - Effects of ragweed and Th-2 cytokines on the secretion of IL-8 in human airway
      epithelial cells.
AB  - Ragweed-induced asthma is a very common pulmonary disease. An important part of
      asthma is a large increase in inflammatory cells, including neutrophils and
      eosinophils, in ragweed-sensitilized subjects. In this study, we determined if
      ragweed treatment could induce the release of interleukin-8 (IL-8) by human
      airway epithelial cells. We found that ragweed induces a substantial increase of
      the secretion of IL-8 from A549 cells in a dose- and time-dependent manner. Th-2
      cytokines, IL-4 and IL-13, partially inhibited the ragweed-induced secretion of
      IL-8. Our results suggest that airway epithelial cells may be one of the cell
      sources that provide IL-8 during ragweed-induced asthma. The results also
      indicate that IL-4 and IL-13 may exert inhibitory effects on IL-8 secretion by
      airway epithelium.

PMID- 10923243
TI  - Asbestos exposure induces MCP-1 secretion by pleural mesothelial cells.
AB  - We showed previously that both crocidolite and chrysotile asbestos inhalation
      induced a persistent macrophage inflammatory response within the pleural space of
      the rat. We postulated that the stimulus for pleural macrophage recruitment after
      asbestos exposure was the induction of monocyte chemoattractant protein-1 (MCP-1)
      synthesis by pleural mesothelial cells. To test this hypothesis, rat pleural
      mesothelial cells (RPMC) were cultured with or without chrysotile or crocidolite
      asbestos fibers (8 micrograms/cm2) in the presence (50 ng/mL) or absence of
      either tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta).
      MCP-1 mRNA expression was assessed by RT-PCR in RPMC cultured for 2 to 24 hours,
      and MCP-1 protein secretion was measured by ELISA in conditioned medium from 24
      hour and 48-hour cultures. Crocidolite and chrysotile fibers induced MCP-1 mRNA
      expression in RPMC which was maximal after 12 hours in the absence of cytokines,
      but which peaked after 2 hours when RPMC were challenged with asbestos + TNF
      alpha or IL-1 beta. Both types of asbestos also significantly increased MCP-1
      protein secretion after 24 and 48 hours (P < .0001), an effect that was
      potentiated by cytokine stimulation. Rats exposed by inhalation to either
      chrysotile or crocidolite asbestos fibers also had greater amounts of MCP-1
      protein in their pleural lavage fluid than did sham-exposed rats. These findings
      suggest that MCP-1 secretion by RPMC may have a role in the initiation and/or
      potentiation of asbestos-induced pleural injury.

PMID- 10923244
TI  - KPL1, which encodes a novel PH domain-containing protein, is induced during
      ciliated cell differentiation of rat tracheal epithelial cells.
AB  - Using differential display, we have identified a novel gene, KPL1, induced in rat
      tracheal epithelial (RTE) cells grown under conditions which stimulate
      ciliogenesis. The KPL1 protein is predicted to contain a pleckstrin homology (PH)
      domain, which has been found in numerous signal transduction and cytoskeletal
      proteins. These domains are thought to function by recruiting proteins to
      cellular membranes, and they have been shown to bind phosphoinositols and the
      beta/gamma subunit of G proteins. We have cloned rat and human KPL1; the
      predicted protein translations are 94% identical. Alternate transcripts exist in
      rat and human tracheal cells that predict a protein which contains a 35-amino
      acid insert. KPL1 was upregulated in RTE cultures undergoing mucociliary but not
      squamous differentiation; and in cultures undergoing mucociliary differentiation,
      KPL1 expression most closely paralleled that of a marker of ciliated cell
      differentiation (axonemal dynein heavy chain) and not a marker of mucous cell
      differentiation (mucin 5AC). As a new member of the family of PH domain
      containing proteins, KPL1 may have a unique role in ciliated cell differentiation
      or function.

PMID- 10923245
TI  - Paradoxical effects of exogenous proteins on lung function in surfactant
      deficient rats.
AB  - Leakage of plasma proteins into the alveolar space can inhibit pulmonary
      surfactant function and worsen respiratory failure in ventilated preterm infants.
      We tested the effect of intratracheal instillation of fetal calf serum (FCS) and
      fresh frozen plasma (FFP) on lung function in ventilated rats who were made
      surfactant-deficient by saline lavage. Post lavage, the rats were treated with
      air placebo, Survanta, FCS or FFP, air placebo + FCS or FFP 1 hour post lavage,
      or Survanta + FCS or FFP 1 hour post lavage. After 2 hours of ventilation,
      pressure volume curves were performed and the lungs relavaged. FCS instillation
      rapidly improved oxygenation when given immediately post lavage or 1 hour after
      placebo or Survanta instillation, whereas FFP instillation never improved
      oxygenation. FCS instillation increased post-treatment lavage phospholipid
      values, but FFP did not. Both FCS and FFP decreased lung volume, but the negative
      effect of FFP exceeded that of FCS. Surfactant aggregate sizing of the final lung
      lavages by dynamic light scattering showed a definite shift towards smaller
      aggregates after FFP, but not after FCS, instillation. These data suggest that
      intratracheal instillation of FCS improves oxygenation and preserves the alveolar
      presence of phospholipids and large surfactant aggregates, whereas FFP decreases
      oxygenation and surfactant aggregate size in surfactant-deficient lavaged rats.

PMID- 10923246
TI  - Pulmonary vascular remodeling distal to pulmonary artery ligation is accompanied
      by upregulation of endothelin receptors and nitric oxide synthase.
AB  - There is increasing evidence that the pathogenesis and progression of many forms
      of pulmonary vasculopathy are related to abnormalities in endothelial mediators,
      including endothelin-1 (ET-1) and nitric oxide (NO). Using a rat model of chronic
      unilateral pulmonary artery ligation, we investigated the role of ET-1 and NO in
      postobstructive pulmonary vasculopathy (POPV). Eight months after a left
      thoracotomy with either left main pulmonary artery ligation (ligated group) or no
      ligation (sham group), rat lungs, including those contralateral to the ligation
      (hyperperfused group), were fixed and mounted for histologic sectioning.
      Morphometric measurements were carried out by computer-assisted image analysis
      and immunohistochemical staining was performed using specific antibodies against
      ET-1, ETA, and EBB receptors, and endothelial NO synthase (eNOS). Compared to
      sham lungs, the ligated lungs showed (1) an increase in muscular, adventitial,
      and intimal thickness of pulmonary artery; (2) increase in external diameter of
      the bronchial artery (39.8 +/- 2.2 microns vs. 16.8 +/- 0.9 microns in sham
      group; P < .005) and number of bronchial arteries per bronchiole (3.21 +/- mu
      0.26 vs. 1.86 +/- mu 0.21 in sham group; P < .001); and (3) increase in the
      intensity of eNOS and ETA, B receptor immunoreactivity. No morphometric or
      immunohistochemical differences were observed between the hyperperfused and sham
      lungs. These findings suggest that increased synthesis of endothelial NO may
      serve as a compensatory mediator in ET-1-mediated vascular remodeling.

PMID- 10923247
TI  - [Study presentation: acupuncture for depression and anxiety].

PMID- 10923248
TI  - [The 100th anniversary of Gustav Wilhelm Storring's "Lectures on
      Psychopathology". A review of his early years].
AB  - The aim of this essay is to retell the life and work of philosopher and
      psychiatrist Gustav Wilhelm Storring (1860-1946) during his early years in
      Leipzig and Erdmannshain. His "Lectures on Psychopathology and its Impact on
      Normal Psychology", written 100 years ago, are acknowledged as his most important
      work. With this book Storring stands in opposition to many of his contemporaries,
      which is illustrated with his concept of mania. In some aspects, however, his
      ideas coincide with those of other well-known psychiatrists such as Emil
      Kraepelin. Both were inclined to the idea that psychiatry and psychology could
      mutually stimulate each other. Storring's work in Wundt's laboratory of
      experimental psychology had a major impact on his work. Wundt's ideas gave
      impetus to a lot of his work and also influenced papers Storring was to write
      later on. Storring's biography is followed until 1902 when he was appointed
      professor of philosophy of Zurich University, in which his friend Ernst Meumann
      was substantially involved. In Leipzig Storring had started his work as
      Flechsig's assistant at the hospital of psychiatry and neurology of Leipzig
      University. In 1897 he founded his own sanitarium for mentally and neurologically
      ill in Erdmannshain, a village near Leipzig, which he managed together with his
      wife Marie, nee Bonacker. With the help of Wundt Storring qualifies as a
      university lecturer. During the years regarded here, however, he got more and
      more attracted to philosophical matters, thus turning away from neurosciences. In
      time he started to regard his work as physician as nothing more than necessary
      for making his living. His relationship with Wundt, who together with his
      laboratory of experimental psychology had previously made him wish to come to
      Leipzig, cooled down, at least on the part of the first. That puts an end to
      Storring's early years not only from the point of view of his biography but also
      from his work.

PMID- 10923249
TI  - [The function of shame in depressive disorders].
AB  - Beginning with the view of the function feelings of shame for psychiatric
      disturbances the relationship between shame and affective disorders was
      described. In a sample of 113 inpatients with depressive symptoms and 81 healthy
      controls, the relationship between shame, trait-anxiety and intolerance of
      ambiguity was examined. The results showed that the clinical group scored higher
      on all measures than the control group. Furthermore, the potential impact of
      publicity was demonstrated in an experimental varied scenario. Individuals with
      high shame level expected a stronger intervention after a norm violation than
      individuals with low shame level. The results were discussed on the background of
      the function feelings of shame for affective disorders.

PMID- 10923250
TI  - [Diagnostic steps in Alzheimer dementia before treatment with new
      antidimentives].
AB  - The dementia of the Alzheimer type (DAT) is a chronic neurodegenerative illness.
      It will continue to increase because of rising life expectancy in the
      industrialized countries. Apart from the physicians interest to treat, there is
      also an economically justified interest to reduce the disease progression in this
      group of patients. The main intention of the treating physicians is to keep their
      patients independent as long as possible. Up to now Alzheimer's disease can only
      be treated symptomatically. The verified diagnosis of DAT still depends on the
      neuropathological investigation of brain tissue. Therefore the clinical diagnosis
      of DAT during lifetime should be supported by chemical analysis of typical
      changes in the cerebrospinal fluid (CSF) at an early stage. Meanwhile, several
      therapeutics with proven effectiveness in clinical studies are certified for the
      symptomatic treatment of DAT. However, these therapeutics are still relatively
      expansive. Due to this fact the clinical diagnosis of DAT should be supported by
      clinical-chemical markers before the beginning of such a treatment. In this paper
      we present the diagnostic steps in dementia patients, who are examined in our
      departments. Patients suspicious of DAT always are asked for a spinal tap in
      addition to other diagnostic tools. In case of a typical clinical constellation,
      the exclusion of a primarily vascular dementia as well as the proof of decreased
      A beta 1-42 peptides and an increased tau protein in CSF we recommend the new
      drugs for DAT as meaningful and justified therapeutics to yield optimal
      treatment.

PMID- 10923251
TI  - [Loss of activities of daily living function (ADL) and cognitive impairment in
      various stages of dementia. A comparison of ADL informant ratings, ADL self
      ratings and psychometric test results].
AB  - In addition to cognitive performance tests, the assessment of activities of daily
      living (ADL) is becoming increasingly important in diagnosing and following up
      dementia. Therefore, we compared results obtained from ADL informant and self
      reports and from the SKT short test for assessing deficits of memory and
      attention. Data were available from a total of 193 elderly subjects in different
      stages of cognitive decline (GDS stages 1-5). First, we determined for each GDS
      group separately the numbers of subjects assessed as being impaired by each of
      the three methods alone as well as in combination. Furthermore, the contribution
      of the two ADL measures, the SKT total score, age, depression and education in
      the prediction of the global severity assessment according to GDS was evaluated.
      Finally, the influence of the latter three variables on the ADL and SKT results
      was estimated by existing correlations. In GDS stage 2, ADL self rating was the
      only approach revealing impairment with a majority of patients. The number of
      patients assessed as being impaired by ADL informant ratings and the SKT only
      increased after GDS stage 2. Analyses of patterns of impairment showed that 66%
      of subjects in GDS stage 1 were rated as unimpaired by each of the three methods.
      Of patients classified as GDS 4 and 5, 85% and 92% respectively were unanimously
      rated as impaired. In GDS stages 2 and 3 a great heterogeneity of patterns was
      found. In a logistic regression model predicting clinically manifest dementia
      symptomatology (GDS 4 + 5 vs GDS 1 + 2 + 3) the SKT and ADL informant ratings
      were included. In a second model predicting membership in a group without
      cognitive impairment (GDS 1 + 2) or in a group suffering from mild cognitive
      impairment (GDS 3) self-rated ADL and age were additionally entered. Especially
      for an early diagnosis of dementia, on the basis of the study results the usage
      of different assessment methods (ADL informant rating, ADL self rating,
      psychometric test) is suggested.

PMID- 10923252
TI  - [Institutional care for the very old. Results of the Munich study of the very
      old].
AB  - In a two-wave community study in Munich, Germany, a representative sample of 402
      people older than 85 years was restudied 1 year later. In the first cross-section
      a total of 358 (89.1%) subjects were interviewed. One year later 263 (73.5%)
      subjects were reexamined. Several diagnostic systems were used. We analysed the
      living situation in different risk groups. Women, singles and the older ones more
      often lived in institutions. Women suffering from dementia and men suffering from
      depression were more often in homes. Need for care and subjective health status
      influenced the living situation.

PMID- 10923253
TI  - [Diabetic somatic polyneuropathy. Pathogenesis, clinical manifestations and
      therapeutic concepts].
AB  - Diabetic polyneuropathy is the most frequent neuropathy in western countries. In
      Germany, there are 3.5 to 4 million diabetic patients. Diagnosis should rule out
      other polyneuropathies and assess two out of the five diagnostic criteria:
      neuropathic symptoms, neuropathic deficits, pathological nerve conduction
      studies, pathological quantitative sensory testing and pathological quantitative
      autonomic testing. So far, the pathophysiology of diabetic neuropathy remains to
      be fully understood. Among the various pathophysiological concepts are the
      Sorbitol-Myo-Inositol hypothesis attributing Myo-Inositol depletion to the
      accumulation of Sorbitol and Fructose, the concept of deficiency of essential
      fatty acids with reduced availability of gamma-linolenic-acid and prostanoids,
      the pseudohypoxia- and hypoxia-hypothesis attributing endothelial and axonal
      dysfunction and structural lesions to increased oxidative stress and free radical
      production. Obviously, the hyperglycemia induced generation of advanced glycation
      end products (AGEs) also contributes to structural dysfunctions and lesions.
      Elevated levels of circulating immune complexes and activated T-lymphocytes as
      well the identification of autoantibodies against vagus nerve or sympathetic
      ganglia support the concept of an immune mediated neuropathy. The reduction of
      neurotrophic factors such as nerve growth factor, neurotrophin-3 or insulin-like
      growth factors also seems to further diabetic neuropathy. The symmetrical,
      distally pronounced and predominantly sensory neuropathy is far more frequent
      than the symmetrical neuropathy with predominant motor weakness or the
      asymmetrical neuropathy. The painless neuropathy manifests with impaired light
      touch sensation, position sense, vibratory perception and diminished or absent
      ankle deep tendon reflexes. The painful sensory diabetic neuropathy primarily
      affects small nerve fibers and accounts for decreased temperature perception and
      paresthesias. The proximal, diabetic amyotrophy evolves subacutely or acutely,
      induces motor weakness of the proximal thigh and buttock muscles and is painful.
      Cranial nerve III-neuropathy is also painful and has an acute onset. Truncal
      radiculopathy follows the distribution of truncal roots and frequently causes
      intense pain. Autonomic neuropathy occurs with and without somatic neuropathy.
      The most important therapy is to attempt optimal blood glucose control, to reduce
      body weight and hyperlipidemia. Symptomatic therapy includes alpha-lipoic acid
      treatment, as the antioxidant seems to improve neuropathic symptoms. Aldose
      reductase inhibitors might reduce sorbitol and fructose production and normalize
      myo-inositol levels. However, there are no aldose reductase inhibitors available
      in Europe as yet. Evening primrose oil, containing gamma-linolenic acid, might
      improve nerve conduction velocities, temperature perception, muscle strength,
      tendon reflexes and sensory function. Substitution of nerve growth factor showed
      promising results in pilot studies but failed in a large-scale multicenter study.
      Symptomatic pain treatment can be achieved with tricyclic antidepressants,
      selective serotonin reuptake inhibitors, anticonvulsants such as carbamazepine,
      gabapentin or lamotrigine, or anti-arrhythmic drugs such as mexiletine. Topical
      capsaicin application should reduce neuropathic pain but also induces local
      discomfort in the beginning of therapy. Vasoactive substances, so far have not
      proven to be of major benefit in diabetic neuropathy. Physical therapy and
      thorough footcare are of primary importance and allow prevention of secondary
      complications such as foot amputations.

PMID- 10923254
TI  - [Variation in the relative length of chromosomes in mammalian karyotypes.
      Hypothesis of equalizing selection].
AB  - A hypothesis on the selective neutrality of relative lengths of karyotype
      chromosomes was tested. Idiograms expected based on an assumption of selective
      neutrality of chromosome lengths were compared with actual idiograms in more than
      a hundred mammalian species. The observed idiograms differed from those expected
      in a similar manner: in the observed idiograms, the longest chromosomes were
      shorter, and the shortest were longer than expected. It is suggested that
      karyotype chromosome variation is limited by selection against chromosome
      rearrangements that produce very long or very short chromosomes. An analysis of
      reciprocal translocations in the mouse and Drosophila showed that translocations
      generating chromosomes of extreme lengths were more deleterious than those
      generating normal-sized chromosomes. A working hypothesis was advanced stating
      that within-karyotype variation of chromosome lengths is accounted for by two
      factors: chromosome rearrangements and natural selection. Chromosome
      rearrangements tend to randomize relative chromosome lengths in a karyotype,
      whereas natural selection acts to equalize them.

PMID- 10923255
TI  - ["Mode for mutation" in the natural population of Drosophila melanogaster from
      Umani is caused by distribution of a hobo-induced inversion in the regulatory
      region of the yellow gene].
AB  - A mutation outburst of the yellow gene occurred in a Drosophila melanogaster
      population from the town of Uman' from 1982 to 1991 and was associated with the
      instability of several alleles. Molecular genetic analysis revealed a deletion
      variant of the hobo transposable element in the same site of the regulatory
      region of yellow in the mutant alleles and their derivatives. The outburst of the
      yellow-2 mutations was attributed to the spreading of the X chromosome, which
      contained an inversion of the yellow regulatory region, through the population.
      Reinversion resulted in the wild-type phenotype. Crossing lines carrying the
      inversion with laboratory line C(1)DX, ywf induced instability of the yellow
      alleles, which was associated with duplication or multiplication of a fragment of
      the yellow gene. Most derivative lines eventually became stable. The loss of
      instability was not associated with phenotypic changes; molecular genetic changes
      included a loss of the duplicated sequences or a deletion of the inverted
      regulatory region of the yellow gene.

PMID- 10923256
TI  - [Expression of marker genes in muscle fibers after transfection in vivo, mediated
      by lactoferrin].
AB  - The capacity of milk iron-transporting human protein lactoferrin (LF) to deliver
      genetic constructions into cells was studied in an effort to correct hereditary
      defects. The purified LF and LF conjugates containing either polylysine (C-1) or
      both polylysine and ficoll (C-2) were bound to plasmid DNA. These complexes were
      injected into mouse muscles, and the expression of the marker genes was tested
      immunochemically. Mice were transfected with either pDMD1 plasmid carrying a full
      size cDNA for human dystrophin gene or pCMVLacZ plasmid carrying the gene of
      bacterial beta-galactosidase. The marker gene expression was detected in the
      muscular fibers. The dystrophin-positive muscular fibers (DPMF) were revealed in
      mdx mice (a model of Duchenne's dystrophy) in the regions of administration and
      in muscles of the other limbs. beta-Galactosidase activity was revealed only in
      the injected muscles. The highest amount of DPMF (9%) was recorded in mice who
      received the complex of DNA with nonmodified LF. Specific LF-mediated human
      transfection as a means of stimulating the receptor-mediated endocytosis of
      genetic constructions and addressed gene transfer to human muscles are discussed.

PMID- 10923257
TI  - [Homologous recombination between direct repeats of chromosomal segments
      comprising heterozygotic duplications in Escherichia coli].
AB  - In conjugational matings between double mutants for the deo operon of Escherichia
      coli, haploid recombinants and extended tandem duplications deoC deoD/deoA
      deoB::Tn5 with the DeoC+DeoA+DeoB+DeoD- phenotype are formed (the deoD+ allele is
      not expressed due to the polar effect of the Tn5 insertion). Selection for the
      expression of the recessive deoC deoD alleles (in the thyA genome) leads to the
      segregation of haploid clones by duplications and also of clones that retain the
      diploidy but that are homozygous for deoC deoD. In addition to haploids, diploid
      clones retaining the duplications have also been found among the DeoD+
      segregants. The phenotype of segregants retaining the duplication shows that they
      were formed by an unequal exchange between sister chromosomes. A comparison of
      segregation frequency of haploid and diploid DeoD+ clones in rec+ and recBC sbcB
      sbcC strains shows that duplications in the rec+ genome are more stable. On this
      basis, it is assumed that the RecBCD pathway possibly makes a greater
      contribution than the RecF pathway to the preservation of heterozygous
      duplications playing an important role in the evolution of prokaryotes.

PMID- 10923258
TI  - [RAD29 and RAD31--new genes from Saccharomyces cerevisiae yeasts, participating
      in control of DNA repair. Isolation and genetic study of mutants].
AB  - Base excision repair (BER) and nucleotide excision repair (NER) are two main
      cellular responses to DNA damage induced by various physical and chemical
      factors. After exposure of the strain that carries the NER-blocking rad2 mutation
      to UV light, several mutants hypersensitive to the UV light lethal action and
      simultaneously sensitive to methylmethanesulphonate (MMS) were isolated. Two of
      these mutants (Uvs64 and Uvs212) were examined in detail. The mutants were found
      to carry recessive, monogenically inherited lesions that had pleiotropic, though
      different, phenotypes: both mutants were also sensitive to nitrous acid (HNO2),
      whereas Uvs212 was sensitive to hydrogen peroxide as well. Moreover, the
      homozygote for the uvs212 mutation, but not for uvs64, blocks the sporulation.
      Since the mutations examined were not allelic to any of the known rad mutations
      that cause MMS sensitivity or to each other, it is concluded that two new genes
      involved in the control of yeast DNA repair were detected. Furthermore, these
      genes were mapped to different regions of the right arm of chromosome 2 where
      repair genes were not found. Thus, two new genes, designated RAD29(UVS64) and
      RAD31(UVS212) and probably involved in base excision repair, were identified.

PMID- 10923259
TI  - [Response of the MGE 412 pattern to truncation selection of a quantitative trait
      in an isogenic line of drosophila after severe heat shock (SHS)].
AB  - Positive and negative selection on the total length of two fragments of an
      interrupted longitudinal wing vein in an isogenic line of Drosophila melanogaster
      was accompanied by changes in the genomic localization pattern of MGE 412. Strong
      truncation selection was conducted in the population of effective size Ne = 160
      for 50 generations. Twenty-six out of 35 polymorphic HHS-induced segments of MGE
      localization behaved as independent copies and markers, whereas 9 segments proved
      to be selective. The second group included "hot" segments of HHS transposition
      induction (43B, 97E, etc.). Thus, final consensus patterns of induced MGE
      transpositions have a random and an adaptive component in generation 50 of
      positive and negative selection. Selective patterns probably include modifier
      MGEs, which generate induced genetic regulatory variation of polygenes
      controlling the selected quantitative trait in the isogenic line after HHS.

PMID- 10923260
TI  - [Position effect variegation of the mosaic type, arising as a result of
      transposition AR4-24P[white, rosy] in the Drosophila melanogaster genome].
AB  - A line with the mosaic expression of the white+ transgene was obtained by
      inducing transposition of the AR4-24P[white, rosy] transposon and was used for
      the second round of induction. As a result, 57 lines with the mosaic eye
      pigmentation were obtained. In situ hybridization and Southern blotting showed
      that genomic DNA fragments flanking AR4-24 were, in some cases, transposed
      together with the transposon. A spontaneous loss of these fragments resulted in
      reversion to the wild-type phenotype. The mosaic eye pigmentation in a line that
      carried the AR4-24 transposon flanked with the same fragments in region 24D1-2
      was not affected by the Su(var)3-6 gene modifying position effect variegation
      (PEV). Other PEV modifiers, Su(var)3-9 and Su(var)2-5, had only a slight effect
      on PEV; Su(var)3-7 restored the wild-type phenotype. The genomic fragments
      captured by the transposon may contain DNA sequences that autonomously induce
      mosaic PEV of the white gene.

PMID- 10923261
TI  - [Effect of a selective agent and a plant intron on the effectiveness of
      transformation and expression of heterologous genes in the pear (Pyrus communis
      L.)].
AB  - The effect of selective agents on the efficiency of Agrobacterium-mediated
      transformation of pear was shown. The transformation frequency of the pear stock
      PS no. 217 by a binary vector carrying the nptII gene conferring kanamycin
      resistance was 0.4 or 3.1%, while the hpt gene for hygromycin resistance used as
      a selective marker increased transformation frequency to 6.2 (11.5%). In
      addition, upon selection on hygromycin B, the proportion of pseudotransgenic
      regenerants considerably decreased. In four transformation experiments, twenty
      independent clones were recovered, and their transgenic nature was confirmed by
      PCR, histochemical, and fluorometric analyses of GUS activity. The presence of
      introns in the coding region of a heterologous gene was shown to influence the
      efficiency and stability of transgene expression in plant tissues. Fluorometric
      determination of GUS activity conducted for a period of two years demonstrated a
      threefold increase in transgene expression in the case that an intron-containing
      construct was used for transformation. The expression level was rather stable
      across several years. The transformation procedure developed may be used for
      successful expression of heterologous genes controlling agronomic characters in
      pear plants.

PMID- 10923262
TI  - [Characteristics of certain symbiotic pea mutants by traits related to hormonal
      status].
AB  - Association between traits for hormonal status and nodulation in the mutants of
      pea Pisum sativum L. with abnormal nodulation and original forms was analyzed.
      The sensitivity of plant tissues to exogenous phytohormones and changes in the
      concentration of the major auxin, indolyl-3-acetic acid, in plant roots during
      interaction with rhizobia were examined. Association between Nod(++)-phenotype
      and auxin balance was revealed: the supernodulating mutants were more sensitive
      to auxin treatment than the parental cultivars. Mutations in the sym8 gene, in
      contrast to those in the sym5 gene, had no effect on plant hormonal status. The
      level of indolyl-3-acetic acid during interaction with rhizobia depended on the
      time after inoculation and plant genotype. The mutations affecting nodulation
      were suggested to change auxin level in roots.

PMID- 10923263
TI  - [RAPD-analysis of duck genetic polymorphisms. Interlineal differences in a Peking
      duck species].
AB  - The possibility of using RAPD markers for the detection of differences between
      lines of Peking duck constituting a local population maintained at the
      Blagovarskii State Farm for Pedigree Poultry was demonstrated. Genetic distances
      based on the RAPD markers precisely and accurately reflect even small changes
      that occurred in the genetic structure of Peking duck lines during breeding of
      parental forms. The pattern of inheritance of RAPD markers obtained using primer
      HM13 was studied in the F1 progeny of two families. The results can be used for
      improvement of available high-productivity lines of ducks breeding of new lines,
      and promotion of the combining abilities of lines.

PMID- 10923264
TI  - [Mutations hooded and nonagouti in the gray rat (Rattus norvegicus): effect of
      selection on behavior and photoperiod].
AB  - Selection of wild Norway rats for behavior conducted in different directions was
      shown to affect the rate of appearance of coat-color mutants. In the population
      selected for domestication (reduced aggressive-fearful behavior toward humans),
      almost all animals acquired the semirecessive mutation hooded (h). Selection for
      aggressiveness (enhanced aggressive-fearful response) was accompanied by an
      increase in the frequency of homozygotes for a recessive mutation nonagouti (a).
      In the population selected for aggressive behavior, seasonal variation in the
      rate of appearance of mutant animals was observed. Experiments on the maintenance
      of nonselected rats under artificial short-day conditions showed possible
      interaction between alleles Agouti (A) and nonagouti but exclusively in
      heterozygotes for hooded. This interaction may lead to the inactivation of the
      normal A allele in some AaHh heterozygotes and their transformation into aa
      homozygotes, which would resemble paramutation. Discussion of the results is
      focused on several issues: recent evidence on coat-color genes and their
      function, directional (as opposed to random) nature of appearing mutations, and
      the possibility of meiotic inheritance of genetic changes occurring in early
      development.

PMID- 10923265
TI  - [Effect of selection for behavior on the cranial traits of the American mink
      (Mustela vison)].
AB  - Cranial sizes of American mink selected for tame and aggressive behavior (towards
      humans) and control mink, which were not selected for behavior, were compared.
      Absolute sizes of the skull were demonstrated to change depending on the
      direction of selection. Sexual dimorphism was reduced in mink selected for
      aggressive behavior, because the cranial sizes of females increased and those of
      males decreased. Cranial traits were analyzed by the method of principal
      components. The groups studied differed from one another with respect to the
      first four components. Although the vector of selection determined the
      differences between the groups, some morphological changes were similar in the
      groups selected for tame and aggressive behavior.

PMID- 10923266
TI  - [Formation of a gene pool of miniature Siberian swine "Minisibs" and their use in
      medico-genetic research].
AB  - The results of 35-year breeding of a new variety of laboratory animals for
      biological and medical studies, termed Minisibs (miniature Siberian swine), are
      summarized. Minisibs were obtained via hybridization between Swedish Landrace
      pigs, who have an epistatic white coat color, and black Vietnamese masked pigs of
      breed I, who have genes of dwarfism. Some genes of wild boars Sus scrofa scrofa
      and S. s. nigripes from Central Europe and Central Asia, respectively, were
      introduced to the Minisibs gene pool in order to strengthen the constitution,
      increase the general resistance, and improve the functions of the cardiac muscle
      and valves. The pigs were selected for a decrease in body weight and an increase
      in litter size over 15 generations. Immunogenetic and chromosomal polymorphisms
      were constantly monitored by Robertsonian translocations Rb 15/17 and Rb 16/17
      introduced from boars. Long-term breeding produced a population of laboratory
      pigs with an average adult weight of approximately 60 kg, a litter size of seven
      to eight piglets, and quiet behavior. Most of animals used in selection were
      white, which is essential for radiobiological experiments and studies on skin
      histocompatibility. Introduction of chromosomal polymorphism to the minipig gene
      pool and long-term immunogenetic and cytogenetic monitoring made it possible to
      perform subchromosomal mapping of the loci of some blood-group systems associated
      with the loci controlling coat color, litter size, stress resistance and meat
      quality (halothane sensitivity), and histocompatibility. Minisibs have been
      successfully used in numerous biomedical studies and in therapeutic and surgical
      cardiology (for production of diagnostic sera controlling lipid metabolism and of
      biological prostheses of cardiac valves). The anatomical and physiological
      similarity of Minisibs to humans indicate that these animals may serve as donors
      of xenografts for orthotopic heart transplants to humans.

PMID- 10923267
TI  - [Identification of mutations in the arylsulfatase B gene in Russian
      mucopolysaccharidosis type VI patients].
AB  - Molecular genetic analysis of the gene for arylsulfatase B (ASB) was conducted in
      ten Russian patients with type VI mucopolysaccharidosis (MPS VI) of different
      severity. Eight exons from the translated region of the ASB gene of each patient
      were amplified and sequenced using the nonradioactive method. Fourteen mutant
      alleles were identified in the sample studied by means of DNA analysis; 13 of
      them had not been described before. All patients except for one, who was an
      offspring of a consanguineous marriage, were genetic compounds with respect to
      the mutations found. Polymorphic sites A/G 1072 and A/G 1126, which were earlier
      revealed in exon 5 of the ASB gene, were found in five out of ten patients
      studied. The spectrum of mutant alleles of the ASB gene was highly specific and
      agreed with the characteristics of the population genetic load.

PMID- 10923268
TI  - [Analysis of expansion of the triplet repeat (CTG)n in myotonic dystrophy
      patients from Bashkir].
AB  - A method was elaborated for simple and rapid diagnosis of myotonic dystrophy
      (MD). The method consists in estimating expansion of the CTG repeat in the
      myotonin protein kinase gene by means of PCR amplification of a gene fragment
      from genomic DNA and Southern hybridization of the amplified fragments with probe
      (CTG)9. Bashkir patients with Rossolimo-Steinert-Batten-Kurshmann MD were
      examined with this method.

PMID- 10923269
TI  - [Mutation in the structure of exon 7 of the phenylalanine hydroxylase in
      phenylketonuria patients from the Novosibirsk area].
AB  - The spectrum and frequency of mutations of exon 7 of the gene for phenylalanine
      hydroxylase (PAH) were studied in 34 phenylketonuria (PKU) patients living in
      Novosibirsk oblast. The five most prevalent mutations constituted 17.64% of
      defective alleles: R243Q (1.47%), R252W (1.47%), R261Q (5.88%), E280K (1.47%),
      and P281L (7.35%). A neutral polymorphic locus V245V was found within exon 7.

PMID- 10923270
TI  - [Effect of the di mutation (non-sugar diabetes) on properties of kidney proteins
      in rats].
AB  - Renal proteins were studied in Brattleboro rats of the didi genotype and in
      Wistar and Sprague-Dawley rats with normal alleles +2 of this loci. In animals of
      the +2 genotype maintained under conditions of water deprivation, the content of
      120 kDa protein increased significantly in inner medulla of the kidney over 3
      days. No changes in the amount of this protein were observed in rats of the didi
      genotype under the same conditions. We suggest that the congenital inability of
      didi mutants to synthesize vasopressin accounts for the distinctions observed in
      the reactions of rats with different genotypes.

PMID- 10923271
TI  - [A metric based on Malecot's parameters of isolation by distance as a
      characteristics of genetic similarity of populations].
AB  - A new metric based on Malecot's parameters of isolation by distance is proposed
      for estimation of genetic similarity between populations. This metric is in good
      agreement with the angular metric used for estimation of interpopulation genetic
      distances. It is suggested to term the new metric Malecot's metric.

PMID- 10923272
TI  - [Polymorphism of trinucleotide CAG-repeats of the first exon of the androgen
      receptor gene in the Tomsk population].
AB  - Polymorphism of the CAG repeat of exon 1 of the androgen receptor (AR) gene was
      analyzed in the Tomsk population. In total, 12 alleles varying in size from 285
      to 318 bp (21-32 CAG units) were revealed. The allele frequency distribution did
      not differ from the normal one. No difference in allele frequencies was detected
      between men and women of the same generation. The observed heterozygosity was
      equal to the expected one (0.88 +/- 0.03). Compared with other populations, the
      Tomsk population displayed a narrower allele spectrum and a bias of the most
      common allele to a greater repeat number. The results obtained may reflect
      specific population genetic processes characteristic of young developing
      populations.

PMID- 10923273
TI  - Administration of recombinant follicle stimulating hormone in a woman with
      allergic reaction to menotropin: a case report.
AB  - This report describes a patient who experienced a generalized allergic reaction
      to Pergonal during controlled ovarian hyperstimulation in preparation for an
      intracytoplasmic sperm injection procedure for treatment of severe male factor
      infertility. The report describes a successful desensitization protocol which
      allowed the patient to complete her treatment cycle despite the allergic reaction
      to Pergonal. Subsequently recombinant follicle stimulating hormone was used
      successfully in inducing follicular growth in the absence of any allergic
      reactions. Therefore, this report confirms other studies which have suggested
      that an allergic reaction to human menopausal gonadotropins is due to impurities
      in such urine-derived products.

PMID- 10923274
TI  - Ovulation induction and early pregnancy loss in a woman susceptible to autoimmune
      diseases: a possible interrelationship.
AB  - We report a 34-year-old woman with sequentially occurring autoimmune diseases
      that are possibly triggered by numerous ovulation inductions. At the ages of 26
      32 years, she experienced 27 uncontrolled ovulation induction cycles using
      clomiphene citrate (CC) or CC plus human menopausal gonadotropin plus human
      chorionic gonadotropin. She became pregnant at the ages of 27, 30 and 31 with
      subsequent pregnancy loss in the 28th, 8th and 10th week of gestation,
      respectively. Insulin-dependent diabetes mellitus (IDDM) developed at the age of
      28. During the second year of ovulation induction, at the age of 27, she
      developed arthralgia that worsened and became migratory from the age of 31.
      Thrombocytopenia appeared at the age of 33. The diagnosis of systemic lupus
      erythematosus (SLE) and antiphospholipid syndrome (APS) was established at the
      age of 34. To the best of our knowledge, this is the first case of concurrent
      IDDM, SLE and APS in a patient associated with ovulation inductions. Excessive
      levels of estradiol achieved during the ovulation inductions could play a role in
      the expression of multiple autoimmune diseases in the susceptible woman.

PMID- 10923275
TI  - Allergic reaction to a highly purified urinary follicle stimulating hormone
      preparation in controlled ovarian hyperstimulation for in vitro fertilization.
AB  - We report a case of general hypersensitivity-like allergic reactions to
      intramuscular injections of highly purified urinary follicle stimulating hormone
      (uFSH-HP) successfully managed by using intramuscular recombinant FSH (rFSH). The
      patient underwent a first cycle of in vitro fertilization (IVF) and controlled
      ovarian hyperstimulation (COH) was achieved with a combination of gonadotropin
      releasing hormone against (GnRH-a) and uFSH-HP. Because, after oocyte recovery,
      no fertilization occurred, the couple subsequently entered an intracytoplasmic
      sperm injection (ICSI) program. During the COH, the woman developed general
      hypersensitivity-like allergic reactions with itching, redness and swelling.
      Although there was regular follicular growth, the allergic symptoms worsened and,
      on day 8 of COH, the stimulation cycle was suspended. A few months later, the
      patient entered a new ICSI cycle. COH was achieved by using a combination of GnRH
      a and rFSH. The cycle was completed and the patient did not report any allergic
      reaction. To avoid allergic reaction to the protein components of the urine
      derived FSH preparations, the use of rFSH is suggested in those patients who
      present local and/or general hypersensitivity-like allergic reactions.

PMID- 10923276
TI  - Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic
      ovaries.
AB  - Anovulation in women with polycystic ovary syndrome (PCOS) is incompletely
      understood. The concentration of the glycoprotein plasminogen activator inhibitor
      1 (PAI-1) is raised in insulin resistance. This has been described in the
      granulosa and theca cell layers of the animal but not the human ovary. This study
      was performed to investigate the location of PAI-1 in the human ovary and
      investigate whether it may contribute to anovulation in PCOS. PAI-1 was localized
      immunohistochemically and quantitated using computer image analysis in 17 ovarian
      follicles from five women with a diagnosis of PCOS and compared with 15 follicles
      from six normal ovaries. PAI-1 was predominantly found in the granulosa and theca
      cells in both polycystic and normal ovaries. Image analysis did not reveal a
      difference in the PAI-1 signal from polycystic compared with normal ovaries. This
      study shows that PAI-1 plays a role in human ovulation, but its role in PCOS
      requires further research.

PMID- 10923277
TI  - The influence of long-term administration of conjugated estrogens and
      antiandrogens to serum leptin levels in women with polycystic ovary syndrome.
AB  - It is well known that a strong exponential relationship exists between leptin
      levels and body mass index (BMI). The different serum leptin levels, however,
      that are observed for each BMI value, suggest that other factors, as well,
      interfere with leptin secretion. This study was designed in order to estimate
      serum leptin levels in patients with polycystic ovary syndrome (PCOS), before and
      after long-term treatment with conjugated estrogens and antiandrogens. Sixteen
      women with PCOS were included in the study. They were divided into two groups:
      the first group comprised 11 non-obese women (BMI 21.6 +/- 0.5 kg/m2), aged 23.5
      +/- 1.1 years; the second consisted of five obese women (BMI 28.9 +/- 1.5 kg/m2),
      aged 22.8 +/- 1.9 years. Blood samples for leptin measurement were drawn before
      and 2, 4, 6, 9 and 12 months after administration of conjugated estrogens and
      antiandrogens. Our results showed that obese women exhibited higher serum leptin
      levels in all blood samples. Moreover, the administration of conjugated estrogens
      and antiandrogens caused an increase in serum leptin levels in the 2nd, 4th, 6th
      and 9th month in both groups of women. Finally, leptin concentrations during the
      12th month of the treatment returned to basic levels in both groups of women with
      PCOS. Our results support the view that BMI is the main variable that influences
      serum leptin levels, and that the effect of conjugated estrogens and
      antiandrogens on serum leptin concentrations is poor.

PMID- 10923278
TI  - Physical symptoms in premenstrual syndrome are related to plasma progesterone and
      desoxycorticosterone.
AB  - Somatic symptoms in the premenstrual syndrome (PMS) may have an etiology separate
      from that of the mental symptoms. A disturbance in mineralocorticoid action has
      been discussed, as mineralocorticoids regulate water balance.
      Desoxycorticosterone (DOC) is interesting, as it has mineralocorticoid effects
      and is a precursor to the neurosteroid 5 alpha-pregnan-3 alpha,21-diol-20-one
      (THDOC). THDOC is a steroid with direct benzodiazepine-like effects on the GABA-A
      receptor in the brain that is metabolized from DOC within the brain and in the
      periphery. Ten women with PMS having swelling as a major symptom and eight
      controls were recruited. They marked, on a validated visual-analog scale, three
      physical symptoms every evening during one menstrual cycle in conjunction with
      giving blood samples for progesterone and DOC measurements. DOC showed menstrual
      cycle-linked variation correlating with progesterone. There was no difference in
      plasma DOC concentrations between patients and controls. The symptoms reached a
      maximum 1-3 days before the onset of menstruation, with a delay of 3-6 days after
      the hormone peak. DOC was less strongly correlated with the symptoms than
      progesterone. These results do not support the hypothesis that DOC is involved in
      the etiology of physical symptoms in PMS or that physical and mental symptoms
      have separate etiologies.

PMID- 10923279
TI  - Enhancement of human endometrial stromal decidualization by bestatin, an
      aminopeptidase-N inhibitor.
AB  - We have re-evaluated the effects of bestatin, an aminopeptidase-N (CD13)
      inhibitor, on in vitro decidualization of normal human endometrial stromal cells
      by using an in vitro decidualization activity assay. Bestatin did not show any
      effects on the viability of both the decidualizing stromal cells co-stimulated
      with 8-Br-cAMP and bestatin and the 8-Br-cAMP-induced decidualized stromal cells,
      or on prolactin release from the decidualized stromal cells. However, bestatin
      dose-dependently enhanced prolactin release from the decidualizing stromal cells
      co-stimulated with 8-Br-cAMP and bestatin. These results indicate that bestatin
      enhances cAMP-mediated decidualization of human endometrial stromal cells and
      suggests that membrane aminopeptidase-N in the human endometrium is involved in
      the regulation of endometrial differentiation by inhibiting cAMP-mediated
      decidualization signals in endometrial stromal cells.

PMID- 10923280
TI  - Effects of policosanol on postmenopausal women with type II hypercholesterolemia.
AB  - This randomized, double-blind, placebo-controlled study was conducted to
      investigate the efficacy, safety and tolerability of policosanol, a cholesterol
      lowering drug purified from sugar-cane wax, in postmenopausal women with type II
      hypercholesterolemia. A total of 244 women who had experienced the menopause and
      showed elevated serum total cholesterol and low-density lipoprotein cholesterol
      (LDL-C) levels despite 6 weeks on a standard lipid-lowering diet were randomized
      to receive placebo or policosanol 5 mg/day for 12 weeks, after which the dose was
      doubled to 10 mg/day for the next 12 weeks. Policosanol (5 and 10 mg/day)
      significantly lowered LDL-C levels (17.7% and 25.2%, respectively) and total
      cholesterol (12.6% and 16.7%, respectively), as well as the ratios of LDL-C to
      high-density lipoprotein cholesterol (HDL-C) (17.0% and 29.3%, respectively) and
      total cholesterol to HDL-C (16.7% and 27.2%, respectively), compared to the
      baseline and placebo; at the same time, policosanol significantly raised HDL-C
      levels by 16.5% and 29.3%, respectively. The drug was safe and well tolerated. No
      drug-related adverse events were observed, and even the extent of adverse events
      was less in the policosanol group than in the placebo group. Four serious adverse
      events occurred in the placebo group (one myocardial infarction, two cases of
      hypertensive status and one surgical intervention) compared to none in the
      policosanol group. In conclusion, policosanol is effective, safe and well
      tolerated in hypercholesterolemic postmenopausal women.

PMID- 10923281
TI  - Influence of obesity and menopausal status on serum leptin, cholecystokinin,
      galanin and neuropeptide Y levels.
AB  - Obesity occurs in 60% of women after menopause and is characterized by an excess
      of adipose tissue that depends on several orexigenic (neuropeptide Y (NPY)
      stimulates carbohydrate ingestion, galanin stimulates fat intake) and anorectic
      (leptin, cholecystokinin (CCK)) factors. Both leptin and insulin can reduce
      hypothalamic NPY production and secretion. Behavior related to the consumption of
      food is probably attributed to the NPY-galanin signalling route. We investigated
      basal levels of serum leptin, CCK, galanin and NPY in 16 non-obese premenopausal
      women, in 15 obese premenopausal women (body mass index (BMI) 34.6 +/- 1.3 SD)
      and in ten obese postmenopausal women (BMI 34.7 +/- 1.5 SD) to determine the
      relationship between obesity, menopause and these neuropeptides. Obese
      premenopausal women had three-fold elevations of serum leptin (32.1 +/- 3.2
      ng/ml) in comparison to non-obese premenopausal women (10.3 +/- 1.5 ng/ml), but
      similar levels to those in obese postmenopausal women (35.3 +/- 4.1 ng/ml). In
      all 44 patients and in both sub-groups of premenopausal and postmenopausal women,
      serum leptin exhibited a strong positive correlation with BMI (r = 0.8692, p <
      0.0001; r = 0.8803, p = 0.0001; r = 0.8184, p = 0.0001, respectively). Serum
      galanin values showed a statistically significant increment in the obese
      postmenopausal group (51.1 +/- 8.1 pg/ml) compared to both premenopausal groups:
      the non-obese (34.9 +/- 5.8 pg/ml) and the obese (36.0 +/- 5.5 pg/ml). Non-obese
      menstruating women demonstrated NPY levels (175.0 +/- 12.8 pg/ml) significantly
      higher than those of obese premenopausal women (126.0 +/- 12.1 pg/ml) and obese
      postmenopausal women (138.1 +/- 15.4 pg/ml). CCK values showed no differences
      between non-obese and obese pre- and postmenopausal groups. Basal insulin values
      were elevated in both obese groups compared to non-obese premenopausal women.
      Significantly increased leptin and galanin levels in postmenopausal obese women
      coupled with decreased NPY levels revealed some changes in the neuropeptides
      regulating eating behavior, which may be the reason for the onset of
      postmenopausal obesity.

PMID- 10923283
TI  - Having a baby: a 'gift from God', or a custom-made purchase?

PMID- 10923282
TI  - Effect of an oral contraceptive containing drospirenone on the renin-angiotensin
      aldosterone system in healthy female volunteers.
AB  - Drospirenone is a new synthetic progestogen with both progestational,
      antimineralocorticoid and antiandrogenic properties. In combination with
      ethinylestradiol, it is being developed as an oral contraceptive which will
      contain 30 micrograms ethinylestradiol and 3 mg drospirenone (Yasmin, Schering
      AG, Germany). The effects of drospirenone alone, and in combination with
      ethinylestradiol, upon the renin-angiotensin-aldosterone system (RAAS) have been
      evaluated in healthy female volunteers. RAAS activity was assessed by measurement
      of plasma renin substrate (PRS) concentration (otherwise known as
      angiotensinogen), plasma renin activity (PRA), and plasma aldosterone (P-Aldo)
      concentration. An antimineralocorticoid effect was observed when volunteers
      received drospirenone alone at doses in the range 0.5-3.0 mg/day for one cycle.
      The effect was dose-dependent for P-Aldo but was not dose-dependent for PRA. When
      ethinylestradiol (30 micrograms) was combined with either 2 mg or 3 mg
      drospirenone and given to volunteers for three cycles, an increase in PRS was
      observed with both preparations, which was indicative of estrogenic stimulation,
      and increases in PRA and P-Aldo were shown which were indicative of an
      antimineralocorticoid effect of drospirenone. Increases in PRA and P-Aldo were
      significantly higher with the preparation containing 3 mg drospirenone in cycle 1
      but not in cycle 3. The effect of the preparation containing 30 micrograms
      ethinylestradiol/3 mg drospirenone upon RAS activity was also compared with that
      of a commercially available preparation also containing 30 micrograms
      ethinylestradiol but combined with 150 micrograms desogestrel (Marvelon). Over a
      period of 13 cycles, increases in PRS were seen with both treatments, the effect
      being slightly more pronounced with 30 micrograms ethinylestradiol/150 micrograms
      desogestrel. A markedly greater increase in PRA was seen following treatment with
      30 micrograms ethinylestradiol/3 mg drospirenone, and, in cycle 3, this
      difference was statistically significant. In contrast, P-Aldo was increased
      markedly with 30 micrograms ethinylestradiol/3 mg drospirenone in all measured
      cycles, whereas, in the 30 micrograms ethinylestradiol/150 micrograms desogestrel
      group, changes were minimal. The increases in PRA and P-Aldo are interpreted as
      endogenous counter-regulation against the antimineralocorticoid activity of
      drospirenone. PRS increases under all combinations are an expression of
      estrogenic stimulation. Measurement of body weight and blood pressure in the
      studies with combined ethinylestradiol and drospirenone revealed that
      drospirenone was associated with either stable body weight or with a slight loss
      in body weight, while blood pressure remained largely unchanged. Overall, the
      results indicate that 30 micrograms ethinylestradiol/3 mg drospirenone has a
      distinct antimineralocorticoid effect.

PMID- 10923284
TI  - [Susceptibilities of bacteria isolated from patients with lower respiratory
      infectious diseases to antibiotics (1998)].
AB  - The bacteria isolated from the patients with lower respiratory tract infections
      were collected by institutions located throughout Japan, since 1981. Ikemoto et
      al. have been investigating susceptibilities of these isolates to various
      antibacterial agents and antibiotics, and analyzed some characteristics of the
      patients and isolates from them each year. Results obtained from these
      investigations are discussed. In these 18 institutions around the entire Japan,
      532 strains of presumably etiological bacteria were isolated mainly from the
      sputa of 438 patients with lower respiratory tract infections during the period
      from October in 1998 to September in 1999. MICs of various antibacterial agents
      and antibiotics were determined against 85 strains of Staphylococcus aureus, 100
      strains of Streptococcus pneumoniae, 96 strains of Haemophilus influenzae, 75
      strains of Pseudomonas aeruginosa (non-mucoid strains), 6 strains of Pseudomonas
      aeruginosa (mucoid strains), 38 strains of Moraxella subgenus Branhamella
      catarrhalis, 26 strains of Klebsiella pneumoniae etc., and the susceptibilities
      of 517 strains were assessed except for those strains that died during
      transportation. S. aureus strains for which MICs of oxacillin (MPIPC) were higher
      than 4 micrograms/ml (methicillin-resistant S. aureus: MRSA) accounted for 60.0%.
      Vancomycin (VCM) and arbekacin (ABK) showed the most potent activities against
      MRSA. But one of MRSA showed resistance to ABK with the MIC of 64 micrograms/ml.
      The sensitive strains of MRSA to VCM have decreased. The frequency of penicillin
      (PC)-intermediate S. pneumoniae (PISP) + PC-resistant S. pneumoniae (PRSP) have
      increased in 46.0% for 1998 comparatively from 30.9% of 1997's. But PRSP
      decreased, and PISP increased into 39.0% of 1998 years from 19.8% of 1997's.
      Panipenem (PAPM), imipenem (IPM) and faropenem (FRPM) showed the most potent
      activities against S. pneumoniae with MIC80s of 0.125 microgram/ml or below.
      Against H. influenzae and M. (B.) catarrhalis, almost all the drugs showed good
      activities. The sensitive strains of them against ceftazidime (CAZ) decreased in
      1997, but those have increased in 1998. Inversely, the susceptibility of them
      against cefotiam (CTM) had been higher in 1997, but those have been lower in
      1998. Tobramycin (TOB) showed the most potent activity against P. aeruginosa
      (both mucoid and nonmucoid strains). All drugs except ampicillin (ABPC) were
      active against K. pneumoniae. A quite few of K. pneumoniae showed low
      susceptibilities. Also, we investigated year to year changes in the
      characteristics of patients, their respiratory infectious diseases, and the
      etiology. The examination of age distribution indicated that the proportion of
      patients with ages over 70 years was 48.6% of all the patients showing a slight
      increase in every year. About the proportion of diagnosed diseases as follows:
      Bacterial pneumonia was the most frequent with 40.2%. The ratio of it has
      increased slightly, and the increased rate was 10% in patients with ages over 70
      years compared with the results in 1997. Chronic bronchitis have decreased
      slightly with 27.6% in 1998. Number of strains isolated from patients before
      administration of antibiotics were more than those after administration of them
      in chronic bronchitis, but these were almost same number in bacterial pneumonia.
      Administration of antibiotics has changed the results of the frequency of
      isolation of bacterial species. Bacterial isolations before administration of
      antibiotics were as follows: S. pneumoniae 26.7%, H. influenzae 23.8%, S. aureus
      13.3% and M. (B.) catarrhalis 10.8%. The frequencies of S. aureus decreased after
      antibiotics administration over 15 days, but the frequencies of P. aeruginosa
      (both mucoid and non-mucoid) was not affected. The frequencies of P. aeruginosa
      was 45.5% after administration over 15 days. The frequencies of S. pneumoniae
      decreased upon administration of antibiotics, these were only 4.5% over 15 days.
      The frequencies of H. (

PMID- 10923286
TI  - Cell and Tissue Engineering. Proceedings of a symposium. Big Sky, Montana, USA.
      June 16-20, 1999.

PMID- 10923285
TI  - [Comparative studies on activities of antimicrobial agents against causative
      organisms isolated from patients with urinary tract infections (1998). III.
      Secular changes in susceptibility].
AB  - Susceptibilities to various antimicrobial agents were examined for Enterococcus
      faecalis, Staphylococcus aureus, Echerichia coli, Klebsiella spp. and Pseudomonas
      aeruginosa that were isolated from patients with urinary tract infections (UTIs)
      in 9 hospitals during June 1998 to May 1999, and the results were compared with
      those obtained during the same period from 1990 to 1997 in uncomplicated UTIs and
      complicated UTIs. Among E. faecalis strains, those with low susceptibilities to
      almost drugs have increased in the latest period. All 5 S. aureus strains
      isolated from uncomplicated UTIs were the most susceptible to gentamicin (GM).
      Over 50% of S. aureus strains isolated from complicated UTIs were susceptible to
      GM, and on the contrary the resistant strains have increased with the MIC90 of
      256 micrograms/ml or above. Among S. aureus strains isolated from complicated
      UTIs, those with low susceptibilities to arbekacin (ABK) have increased in the
      latest period compared to those during period of 1996-1997, and the MIC90s of
      them have changed into the lower state from 1 microgram/ml in 1996-1997 to 4
      micrograms/ml in 1998. S. aureus strains have continued high susceptibilities to
      vancomycin (VCM). The susceptibilities to minocycline (MINO) of E. coli showed
      MIC90: 4 micrograms/ml in 1997, but those have returned in the latest period in
      uncomplicated UTIs. The MIC90s of ofloxacin (OFLX) to E. coli isolated from
      uncomplicated and complicated UTIs have been lower 2-3 classes in the latest
      period than those in 1997. Among Klebsiella spp. strains isolated from
      uncomplicated UTIs, those with low susceptibilities to almost cephems had
      increased in 1997, but few of them were detected in the latest study. The
      sensitive strains of P. aeruginosa to almost drugs have increased during the
      latest period. The MIC50s of cefozopran (CZOP) and OFLX against P. aeruginosa
      were the best in our history. The sensitive strains of P. aeruginosa to
      ceftazidime (CAZ) have increased and its percentage was 30%. Piperacilline
      (PIPC), cefoperazone (CPZ), GM and OFLX resistant P. aeruginosa strains have
      increased in the latest period.

PMID- 10923287
TI  - Scaffolds for engineering smooth muscle under cyclic mechanical strain
      conditions.
AB  - Cyclic mechanical strain has been demonstrated to enhance the development and
      function of engineered smooth muscle (SM) tissues, but appropriate scaffolds for
      engineering tissues under conditions of cyclic strain are currently lacking.
      These scaffolds must display elastic behavior, and be capable of inducing an
      appropriate smooth muscle cell (SMC) phenotype in response to mechanical signals.
      In this study, we have characterized several scaffold types commonly utilized in
      tissue engineering applications in order to select scaffolds that exhibit elastic
      properties under appropriate cyclic strain conditions. The ability of the
      scaffolds to promote an appropriate SMC phenotype in engineered SM tissues under
      cyclic strain conditions was subsequently analyzed. Poly(L-lactic acid)-bonded
      polyglycolide fiber-based scaffolds and type I collagen sponges exhibited
      partially elastic mechanical properties under cyclic strain conditions, although
      the synthetic polymer scaffolds demonstrated significant permanent deformation
      after extended times of cyclic strain application. SM tissues engineered with
      type I collagen sponges subjected to cyclic strain were found to contain more
      elastin than control tissues, and the SMCs in these tissues exhibited a
      contractile phenotype. In contrast, SMCs in control tissues exhibited a structure
      more consistent with the nondifferentiated, synthetic phenotype. These studies
      indicate the appropriate choice of a scaffold for engineering tissues in a
      mechanically dynamic environment is dependent on the time frame of the mechanical
      stimulation, and elastic scaffolds allow for mechanically directed control of
      cell phenotype in engineered tissues.

PMID- 10923288
TI  - Mechanisms of stiffening and strengthening in media-equivalents fabricated using
      glycation.
AB  - We have recently reported that glycation can be exploited to increase the
      circumferential tensile stiffness and ultimate tensile strength of media
      equivalents (MEs) and increase their resistance to collagenolytic degradation,
      all without loss of cell viability (Girton et al., 1999). The glycated MEs were
      fabricated by entrapping high passage adult rat aorta SMCs in collagen gel made
      from pepsin-digested bovine dermal collagen, and incubated for up to 10 weeks in
      complete medium with 30 mM ribose added. We report here on experiments showing
      that ME compaction due to traction exerted by the SMCs with consequent alignment
      of collagen fibrils was necessary to realize the glycation-mediated stiffening
      and strengthening, but that synthesis of extracellular matrix constituents by
      these cells likely contributed little, even when 50 micrograms/ml ascorbate was
      added to the medium. These glycated MEs exhibited a compliance similar to
      arteries, but possessed less tensile strength and much less burst strength. MEs
      fabricated with low rather than high passage adult rat aorta SMCs possessed
      almost ten times greater tensile strength, suggesting that alternative SMCs
      sources and biopolymer gels may yield sufficient strength by compositional
      remodeling prior to implantation in addition to the structural remodeling (i.e.,
      circumferential alignment) already obtained.

PMID- 10923289
TI  - Dynamic mechanical stretch of organotypic brain slice cultures induces
      differential genomic expression: relationship to mechanical parameters.
AB  - Although the material properties of biological tissues are reasonably well
      established, recent studies have suggested that the biological response of brain
      tissue and its constituent cells may also be viscoelastic and sensitive to both
      the magnitude and rate of a mechanical stimulus. Given the potential involvement
      of changes in gene expression in the pathogenic sequelae after head trauma, we
      analyzed the expression of 22 genes related to cell death and survival and found
      that a number of these genes were differentially regulated after mechanical
      stretch of an organotypic brain slice culture. Twenty-four hours after stretch,
      the expression of BDNF, NGF, and TrkA was significantly increased, whereas that
      of bcl-2, CREB, and GAD65 was significantly decreased (MANOVA followed by ANOVA,
      p < 0.05). Expression of CREB and GAD65 was negatively correlated with strain,
      whereas expression of APP695 was negatively correlated with strain rate (all p <
      0.05). This study demonstrates that a subset of genes involved in cell death and
      survival are differentially regulated after dynamic stretch in vitro and that the
      expression of specific genes is correlated with mechanical parameters of that
      stretch.

PMID- 10923290
TI  - A novel injectable collagen matrix: in vitro characterization and in vivo
      evaluation.
AB  - We present here a unique engineered collagen formulation that is injectable and
      compacts into a porous viscoelastic solid after implantation, achieving
      completely focal application without cross-linking. This implant provides a
      cohesive continuously porous matrix, as demonstrated by permeability and
      compression experiments. Those experiments also provide initial mechanical
      characterization of the material and establish the ability to modify these
      essential properties by design. Further, the short-term compaction and long-term
      stability of the implant in vivo in terms of both physical and histological
      responses are assessed in an animal model to demonstrate the mechanism of action
      and long-term persistence of this novel material.

PMID- 10923291
TI  - An axisymmetric boundary integral model for incompressible linear
      viscoelasticity: application to the micropipette aspiration contact problem.
AB  - The micropipette aspiration test has been used extensively in recent years as a
      means of quantifying cellular mechanics and molecular interactions at the
      microscopic scale. However, previous studies have generally modeled the cell as
      an infinite half-space in order to develop an analytical solution for a
      viscoelastic solid cell. In this study, an axisymmetric boundary integral
      formulation of the governing equations of incompressible linear viscoelasticity
      is presented and used to simulate the micropipette aspiration contact problem.
      The cell is idealized as a homogeneous and isotropic continuum with constitutive
      equation given by three-parameter (E, tau 1, tau 2) standard linear
      viscoelasticity. The formulation is used to develop a computational model via a
      "correspondence principle" in which the solution is written as the sum of a
      homogeneous (elastic) part and a nonhomogeneous part, which depends only on past
      values of the solution. Via a time-marching scheme, the solution of the
      viscoelastic problem is obtained by employing an elastic boundary element method
      with modified boundary conditions. The accuracy and convergence of the time
      marching scheme are verified using an analytical solution. An incremental
      reformulation of the scheme is presented to facilitate the simulation of
      micropipette aspiration, a nonlinear contact problem. In contrast to the
      halfspace model (Sato et al., 1990), this computational model accounts for
      nonlinearities in the cell response that result from a consideration of geometric
      factors including the finite cell dimension (radius R), curvature of the cell
      boundary, evolution of the cell-micropipette contact region, and curvature of the
      edges of the micropipette (inner radius a, edge curvature radius epsilon). Using
      60 quadratic boundary elements, a micropipette aspiration creep test with ramp
      time t* = 0.1 s and ramp pressure p*/E = 0.8 is simulated for the cases a/R =
      0.3, 0.4, 0.5 using mean parameter values for primary chondrocytes. Comparisons
      to the half-space model indicate that the computational model predicts an
      aspiration length that is less stiff during the initial ramp response (t = 0-1 s)
      but more stiff at equilibrium (t = 200 s). Overall, the ramp and equilibrium
      predictions of aspiration length by the computational model are fairly
      insensitive to aspect ratio a/R but can differ from the half-space model by up to
      20 percent. This computational approach may be readily extended to account for
      more complex geometries or inhomogeneities in cellular properties.

PMID- 10923292
TI  - The micromechanical environment of intervertebral disc cells: effect of matrix
      anisotropy and cell geometry predicted by a linear model.
AB  - Cells of the intervertebral disc exhibit spatial variations in phenotype and
      morphology that may be related to differences in their local mechanical
      environments. In this study, the stresses, strains, and dilatations in and around
      cells of the intervertebral disc were studied with an analytical model of the
      cell as a mechanical inclusion embedded in a transversely isotropic matrix. In
      response to tensile loading of the matrix, the local mechanical environment of
      the cell differed among the anatomic regions of the disc and was strongly
      influenced by changes in both matrix anisotropy and parameters of cell geometry.
      The results of this study suggest that the local cellular mechanical environment
      may play a role in determining both cell morphology in situ and the inhomogeneous
      response to mechanical loading observed in cells of the disc.

PMID- 10923293
TI  - Functional tissue engineering of articular cartilage through dynamic loading of
      chondrocyte-seeded agarose gels.
AB  - Due to its avascular nature, articular cartilage exhibits a very limited capacity
      to regenerate and to repair. Although much of the tissue-engineered cartilage in
      existence has been successful in mimicking the morphological and biochemical
      appearance of hyaline cartilage, it is generally mechanically inferior to the
      natural tissue. In this study, we tested the hypothesis that the application of
      dynamic deformational loading at physiological strain levels enhances chondrocyte
      matrix elaboration in cell-seeded agarose scaffolds to produce a more functional
      engineered tissue construct than in free swelling controls. A custom-designed
      bioreactor was used to load cell-seeded agarose disks dynamically in unconfined
      compression with a peak-to-peak compressive strain amplitude of 10 percent, at a
      frequency of 1 Hz, 3 x (1 hour on, 1 hour off)/day, 5 days/week for 4 weeks.
      Results demonstrated that dynamically loaded disks yielded a sixfold increase in
      the equilibrium aggregate modulus over free swelling controls after 28 days of
      loading (100 +/- 16 kPa versus 15 +/- 8 kPa, p < 0.0001). This represented a 21
      fold increase over the equilibrium modulus of day 0 (4.8 +/- 2.3 kPa). Sulfated
      glycosaminoglycan content and hydroxyproline content was also found to be greater
      in dynamically loaded disks compared to free swelling controls at day 21 (p <
      0.0001 and p = 0.002, respectively).

PMID- 10923294
TI  - Chondrocyte translocation response to direct current electric fields.
AB  - Using a custom galvanotaxis chamber and time-lapse digital video microscopy, we
      report the novel observation that cultured chondrocytes exhibit cathodal
      migration when subjected to applied direct current (DC) electric fields as low as
      0.8 V/cm. The response was dose-dependent for field strengths greater than 4
      V/cm. Cell migration appeared to be an active process with extension of
      cytoplasmic processes in the direction of movement. In some cells, field
      application for greater than an hour induced elongation of initially round cells
      accompanied by perpendicular alignment of the long axis with respect to the
      applied field. Antagonists of the inositol phospholipid pathway, U-73122 and
      neomycin, were able to inhibit cathodal migration. Cell migration toward the
      cathode did not require the presence of serum during field application. However,
      the directed velocity was nearly threefold greater in studies performed with
      serum. Studies performed at physiologic temperatures (approximately 37 degrees C)
      revealed a twofold enhancement in migration speed compared to similar studies at
      room temperature (approximately 25 degrees C). Findings from the present study
      may help to elucidate basic mechanisms that mediate chondrocyte migration and
      substrate attachment. Since chondrocyte migration has been implicated in
      cartilage healing, the ability to direct chondrocyte movement has the potential
      to impact strategies for addressing cartilage healing/repair and for development
      of cartilage substitutes.

PMID- 10923295
TI  - Use of micropathways to improve oxygen transport in a hepatic system.
AB  - Establishing suitable oxygen transport pathways within bioartificial liver
      replacement devices continues to be an important engineering challenge. Oxygen
      delivery is critical since this is one of the nutrients necessary to maintain
      hepatocyte viability and function. In the current study, the microporosity of a
      collagen extracellular matrix has been modified to permit both diffusion and
      convection mass transport. Using fluorescent visualization, the enhancement
      technique was found to extend the oxygen transport distance from 170 microns to
      360 microns. Furthermore, in hepatocyte culture studies, the enhancement
      technique was observed to yield a sixfold increase in the amount of viable
      hepatocytes able to be sustained by a single O2 source. Normalized function
      studies confirm that hepatocyte function was also improved in the enhanced
      collagen configurations.

PMID- 10923296
TI  - Selective modulation of endothelial cell [Ca2+]i response to flow by the onset
      rate of shear stress.
AB  - The response of endothelial cells (ECs) to their hemodynamic environment strongly
      influences normal vascular physiology and the pathogenesis of atherosclerosis.
      Unique responses to the complex flow patterns in lesion-prone regions imply that
      the temporal and spatial features of the mechanical stimuli modulate the cellular
      response to flow. We report the first systematic study of the effects of temporal
      gradients of shear stress on ECs. Flow was applied to cultured ECs using a novel
      cone-and-plate device allowing precise and independent control of the shear
      stress magnitude and the onset rate. Intracellular free calcium concentration
      ([Ca2+]i) increased rapidly following the onset of flow, and the characteristics
      of the transient were modulated by both the shear stress magnitude and onset
      rate. ECs were most sensitive to shear stress applied at physiological onset
      rates. Furthermore, the relative contribution of extracellular calcium and IP3
      mediated release were dependent upon the specific flow regime.

PMID- 10923297
TI  - Effects of heat-induced damage on the radial component of thermal diffusivity of
      bovine aorta.
AB  - The extent of the change in thermal diffusivity of soft tissues due to heat
      induced damage is not well known. Reported here are the results of using the
      flash method to measure the through-the-wall component of thermal diffusivity of
      bovine aorta before and after the tissue has undergone two hours of heating at 75
      degrees C. The measurements indicate a 10.1 percent increase in the thermal
      diffusivity of the tissue post-heating. While this change may not result in a
      significant change in the tissue temperature profile, further study is needed to
      quantify the thermal diffusivity in other coordinate directions, as well as the
      mechanisms by which this change in properties occurs.

PMID- 10923298
TI  - Mechanical properties of a biodegradable bone regeneration scaffold.
AB  - Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer,
      has been shown to have osteoconductive effects in vivo when used as a bone
      regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P.
      S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The
      material properties of the polymer allow it to be injected into irregularly
      shaped voids in vivo and provide mechanical stability as well as function as a
      bone regeneration scaffold. We fabricated a series of biomaterial composites,
      comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta
      TCP), into the shape of right circular cylinders and tested the mechanical
      properties in four-point bending and compression. The mean modulus of elasticity
      in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity
      in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of
      magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent,
      by mass, did not decrease Ec and Eb significantly, but did decrease bending and
      compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to
      0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP
      composites. These results indicate that this biodegradable polymer composite is
      an attractive candidate for use as a replacement scaffold for trabecular bone.

PMID- 10923300
TI  - Cesarean section for all twins?
AB  - Twin gestations frequently involve maternal and fetal complications, and are
      quite often considered as "premium" pregnancies. Hence, many clinicians that
      follow the cliche "no high risk pregnancy should end with a high risk delivery"
      may deliver twins by CS for many subtle reasons, other than clear-cut, evidence
      based, indications. Thus, the decision for a CS in twins, intentionally or not,
      is based on qualitative variables that were not quantified and on quantitative
      variables that suggest no advantage for CS in the majority of cases.

PMID- 10923299
TI  - Biological activity of rhBMP-2 released from PLGA microspheres.
AB  - Human recombinant bone morphogenetic protein-2 (rhBMP-2) has been proven
      effective in stimulating the regeneration of bone in both skeletal and
      extraskeletal locations. Through encapsulation within, and release from,
      biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) microspheres, a proven
      vehicle for sustained delivery of various proteins, the local concentrations of
      rhBMP-2 could be maintained at optimal levels to stimulate bone regeneration and
      remodeling at the site of healing in diverse clinical settings. Thus the purpose
      of this work was to investigate the encapsulation of rhBMP-2 in PLGA microspheres
      and its biologic activity upon release. Using in vitro tests in simulated body
      fluids, the effect of rhBMP-2 released from PLGA microspheres upon osteoblast
      cell cultures was found to be statistically similar to the effect produced by
      positive controls consisting of nonencapsulated aqueous rhBMP-2 in simulated body
      fluids. This clarifies an important step in skeletal tissue engineering
      strategies aimed at the use of encapsulated rhBMP-2 to stimulate bone
      regeneration and remodeling.

PMID- 10923301
TI  - The effects of childbirth on the pelvic-floor.
AB  - Basically, vaginal delivery is associated with the risk of pelvic floor damage.
      The pelvic floor sequelae of childbirth includes anal incontinence, urinary
      incontinence and pelvic organ prolapse. Pathophysiology, incidence and risk
      factors for the development of the respective problems are reviewed. Where
      possible, recommendations for reducing the risk of pelvic floor damage are given.

PMID- 10923302
TI  - Multiple courses of antenatal glucocorticoid treatment and fetal outcome.
AB  - Thanks to the US National Institutes of Health Consensus Conference, the odds of
      antenatal use of glucocorticoids for preventing severe neonatal complications of
      premature delivery have significantly increased these last years. The belief that
      neonatal benefits last up to 7 days after the first course and administration of
      further courses is safe has led many obstetricians to prescribe multiple
      antenatal glucocorticoid courses. Whether multiple courses offer an advantage
      over a single course has not been demonstrated. In contrast, there are
      accumulating evidence suggesting that this practice may have short and long-term
      side effects. The potential benefits and side effects of multiple antenatal
      courses of glucocorticoids, extrapolated from experimental data and observational
      studies, are detailed in this review. Until the results of ongoing randomized
      trials with long term follow-up are available, the practice of giving multiple
      courses of glucocorticoids to women should be considered with the greatest
      caution.

PMID- 10923303
TI  - Three-dimensional sonography in prenatal diagnosis: a luxury or a necessity?
AB  - Three-dimensional sonography revolutionized ultrasound imaging with its capacity
      to depict an unlimited number of planes in which the object of interest can be
      displayed. The addition of numerous modalities of image rendering promotes three
      dimensional sonography to the top of the spectrum of diagnostic imaging in
      obstetrics and gynecology. The aim of this article is to present our experience
      in 3-D sonography during the second and third trimester of pregnancy and to give
      a comparative review of literature. 247 patients in gestational age ranging from
      12 to 40 weeks of gestation were examined over a three year period. The majority
      of patients entered the study because fetal anomaly was suspected at two
      dimensional sonography. Some patients were sent on to three-dimensional
      sonography because it was not possible to depict clearly normal fetal anatomy by
      two dimensional sonography. Out of 170 fetal anomalies three-dimensional
      sonographic analysis failed in only three cases. In all three anomaly was
      accompanied with severe oligohydramnios. Main advantages of three-dimensional
      ultrasound in perinatal medicine and antenatal diagnosis include scanning in the
      coronal plane, improved assessment of complex anatomic structures, surface
      analysis of minor defects, volumetric measuring of organs, "plastic" transparent
      imaging of fetal skeleton, spatial presentation of blood flow arborization and,
      finally, storage of scanned volumes and images. It is our decided opinion that
      three-dimensional sonography has gained a valuable place in prenatal diagnosis,
      becoming a necessity for every modern perinatal unit.

PMID- 10923304
TI  - Does preeclampsia influence fetal lung maturity?
AB  - OBJECTIVE: This retrospective study compared the fetal lung maturity biochemical
      profile of patients having preeclampsia with that of patients having preterm
      labor. STUDY DESIGN: Amniotic fluid was obtained by transabdominal amniocentesis
      in 90 patients, 59 patients with preterm labor (PTL) and 31 patients with
      preeclampsia (PRE). Pregnancies with fetal growth restriction were excluded.
      Fetal lung maturity was assessed by lecithin/sphingomyelin ratio (L/S) and by a
      fluorescence polarimetry assay (FLM). Mean values of L/S ratios and FLM were
      compared between the PTL and the PRE groups, each within two gestational age
      subgroups (27-32.9 weeks gestation and 33-36 weeks gestation). Student t-test,
      Chi-square test Fisher's exact test were used for statistical analysis. A p value
      < 0.05 was considered significant. RESULTS: During the gestational age interval
      of 33-36 weeks, the mean L/S ratios were significantly lower in pregnancies
      complicated by PRE than in those complicated by PTL (1.99 +/- 0.26 and 2.4 +/-
      0.57, respectively; p = 0.01). Similarly, during this gestational age interval,
      the FLM values were also lower in PRE than in PTL, although the difference did
      not reach statistical significance. CONCLUSION: During the gestational age
      between 33 and 36 weeks of gestation, the biochemical profile of preeclamptic
      patients without IUGR has a significant lower L/S ratio compared to that of
      preterm patients.

PMID- 10923305
TI  - Transvaginal volumetry of first trimester gestational sac: a comparison of
      conventional with three-dimensional ultrasound.
AB  - The aim of this study was to determine whether three-dimensional (3D) ultrasound
      is superior to two-dimensional (2D) ultrasound in evaluating first trimester
      gestational sac volume (GSV). 130 mainly low risk pregnancies between 5 and 12
      weeks gestation were prospectively investigated. The 2D volumetry of GSV was
      performed using the ellipsoid formula; the 3D volumetry was carried out in all
      three planes using the contour mode and the volume from the measured
      circumferences and the distances between them were computed by a software. The
      data were analysed by variance and regression. The mean GSV increased from 1.5 +/
      2 ml with 5 weeks to 127 +/- 27 ml with 12 weeks (3D, longitudinal plane). The
      standard deviation of measured GSV increased with gestational age (GA) and GSV,
      and was more evident using 2D than 3D volumetry. GSV of pregnancies with similar
      GA differed considerably and viable pregnancies followed by miscarriage did not
      show different GSV. We conclude, that 3D volumetry of first trimester GSV is
      superior to 2D volumetry in its estimation, but seems to be without a prognostic
      significance for gestational outcome.

PMID- 10923306
TI  - Effect of high amniotic fluid pressure on fetal circulation.
AB  - The purpose of this study was to investigate the effects of high amniotic fluid
      pressure (AFP) created by amnioinfusion on fetal circulation. Five pregnant goats
      whose fetuses had a mean gestational age of 131 +/- 2 days (term 145 days) were
      used. After a 30 minute control period, 1500 ml of warm saline was infused to the
      amniotic cavity over a period of 30 minutes. The AFP gradually increased during
      amnioinfusion and remained 2-3 mmHg above the control level for 3 hours after
      amnioinfusion. Fetal arterial pH (FpH) tended to decrease, and there was a
      significant negative correlation between the FpH and AFP (r = -0.723). Fetal
      arterial pO2 also tended to decrease and negatively correlated to the AFP (r = 
      0.59). On the other hand, fetal arterial pCO2 tended to increase and positively
      correlated with the AFP (r = 0.75). Although amnioinfusion is useful for
      improving the status of a distressed fetus, the fetal condition may be
      jeopardized at the same time. Therefore, careful monitoring of the AFP and fetal
      status is recommended during amnioinfusion.

PMID- 10923307
TI  - Bioelectrical impedance analysis in the clinical management of a pregnant woman
      undergoing dialysis.
AB  - We report a case of successful pregnancy in a woman who was initially diagnosed
      with renal failure in mid-pregnancy. She was started on hemodialysis, and her
      fluid balance was serially monitored with bioelectrical impedance analysis. Her
      body weight decreased and bioelectrical impedance values increased, along with
      resolution of pulmonary edema in the process of the removal of excessive fluid
      retention with hemodialysis. The bioelectrical impedance values decreased
      immediately after the usual dose of oral ritodrine was administered, partly
      because producing sodium and water retention by ritodrine were enhanced in the
      setting of fluid imbalances. This decrease preceded the onset of pulmonary edema,
      while no changes were noted in maternal body weight before hemodialysis. These
      results suggest that the serial measurement of bioelectrical impedance values
      enables more reliable and earlier detection of abnormal water retention in
      pregnant women undergoing dialysis than the effect of body weight changes.

PMID- 10923308
TI  - Comparison of the relaxation effect in vitro of nitroglycerin vs. fenoterol on
      human myometrial strips.
AB  - AIMS: Substance dose-related comparison of relaxation effect of nitroglycerin
      (GTN) and the beta 2-mimetic substance fenoterol in human myometrial tissue.
      METHODS: Test criterion is the isometric force development of isolated human
      myometrial strips. These muscle strips were removed from the lower uterine
      segment at cesarean section. Fenoterol in concentrations of 3 x 10(-8)-10(-5)
      mol/l or GTN in concentrations of 1.7 x 10(-8)-5.8 x 10(-4) mol/l were applied to
      the 2 x 2 x 10-mm strips, which were fixed and maintained in tissue baths. The
      curves were plotted on line. The integral or the "area under the curve" (AUC)
      served as the parameter for muscle strip activity. RESULTS: A total of 100 strips
      from 20 patients were used. GTN demonstrated a significant relaxation effect in
      the in vitro model on human myometrial strips from pregnant women already treated
      with oxytocin. The effect was able to be enhanced to a point where oxytocin
      induced contractions were completely absent. A relatively clear connection was
      demonstrated between dose and effect whereby increased muscle relaxation resulted
      at increased concentrations. Compared to GTN application, muscle strip relaxation
      was less pronounced under fenoterol; a complete inhibition of myometrial activity
      was not achieved under fenoterol. CONCLUSIONS: With respect to relaxation of the
      myometrial tissue samples the NO donor GTN is at least as potent as the standard
      tocolytic agent fenoterol in the in vitro model.

PMID- 10923309
TI  - [Effects of standardized optokinetic stimuli on standing stability].
AB  - BACKGROUND: Human standing stability is ensured by means of a sensory-motor
      control system. Proprioceptivity is most important among sensory afferences. At
      this time, less is known about the effect of standardized visual stimuli on motor
      programs towards support of body stability. These investigations were performed
      with special consideration for different strains on bunions and heels of both
      feet. METHODS: 42 healthy individuals (averaged age 29.6 years) were investigated
      with relaxed standing on the static force platform of Portable Multiplate System
      P. M. S. with optokinetic stimuli in horizontal, vertical and torsional direction
      (speed 80 degrees/s). Conducted by computer-analysis, the stability index,
      varying foot-pressure on heels and bunions, Fourier spectral analysis, and weight
      distribution index were counted. The eye movements were controlled with help of
      the PENG device. RESULTS: The optokinetic stimulations led to partial
      statistically significant impairments of stability particularly with torsional
      stimuli, yet notably improved stability with left stripes pattern. The sensory
      conflict between visual and other sensory inputs led to a statistically
      significant shift of sway frequencies to the higher ranges. On stimulation, the
      distribution of pressure to the feet changed. The preponderance to rest on the
      left side was equalized. The heels were considerably strained more with visual
      stimuli in all directions. Individuals felt more agreeable, toward stripes
      vertically directed while torsionally directed stripes elicited particular
      strain. CONCLUSION: Sensory conflicts between visual and other sensory inputs for
      maintaining the upright body position were found to impair the stability.
      Nevertheless these conflicts were partially compensated by motor programs more
      straining to the heels.

PMID- 10923310
TI  - [Therapy of hyperacusis in patients with tinnitus].
AB  - BACKGROUND: Patients with tinnitus very often suffer from hyperacusis also.
      METHODS AND PATIENTS: In the present study a possible treatment for patients with
      bilateral hyperacusis is introduced and the therapeutical results of 41 patients
      suffering from bilateral hyperacusis combined with a uni- or bilateral tinnitus
      are discussed. Twenty-one of them also had a cochlear hearing loss. By means of
      white noise generators or hearing aids and a specific acoustic training the
      auditory input to the central nervous system was increased. All patients were
      taught a method to reduce stress (Progressive muscle relaxation according to
      Jacobson). Uncomfortable loudness levels were analysed before as well as 3 weeks
      and 6 months after beginning of the treatment. RESULTS: By the time of 3 weeks
      the discomfort from ordinary sounds was distinctly reduced and the reduction
      progressed further after 6 months of treatment. In more than 50% of the
      participants the uncomfortable loudness levels could be raised to a normal range.
      Interestingly the improvement of hyperacusis was independent of an existing
      hearing loss. CONCLUSIONS: The described method of treatment seems to be helpful
      for patients with hyperacusis and will be compared to other therapeutical
      regimes.

PMID- 10923311
TI  - [Round window microcatheter administered microdose of gentamycin: an alternative
      in the treatment of tinnitus in patients with Meniere's disease].
AB  - BACKGROUND: In this study, we review the results of Meniere's disease treatment
      using microdose gentamycin delivered directly to the round window using a new
      microcatheter system. PATIENTS AND METHODS: 11 patients were treated by 1.25 mg
      gentamycin on the 3rd and 7th day after insertion of the new microcatheter at the
      niche of the round window membrane, while a second group of 7 patients was
      treated by a gentamycin dosage of 1 microliter/h continuously applied by a
      minipump over a period of 10 days. Electrocochleography was derived by an
      integrated electrode and the microcatheter was removed after 10 days. The results
      were analysed with a follow-up ranging from 6 to 12 months. RESULTS: In 15 of 18
      patients (83%) tinnitus was improved significantly throughout the follow-up
      period. Vertigo was eliminated in all patients, and pressure was relieved in 17
      of 18 (94%). CONCLUSIONS: These preliminary data suggest that gentamycin
      delivered by the Round-Window-Microcatheter is a safe and effective treatment for
      the reduction of tinnitus, vertigo, and pressure associated with Meniere's
      disease.

PMID- 10923313
TI  - [Coexistence of bilateral paraganglioma of the A. carotis, thymoma and thyroid
      adenoma: a chance finding?].
AB  - Bilateral carotid body tumors are quite rare neoplasms. The coexistence of
      bilateral carotid body tumor, thyroid gland adenoma and thymoma has not yet been
      reported in the literature. We report on a 59-year old male who presented with a
      bilateral cervical mass. After the standard diagnostic procedures and surgical
      removal the diagnosis of a carotid body tumor was confirmed. On physical
      examination, the carotid body tumor is usually palpable as a firm, painless
      cervical mass. Even though carotid body tumors are slow-growing, and from a
      histological point of view benign, they sometimes attain massive size and
      therefore compress the surrounding tissue and create clinical pressure symptoms.
      A hereditary-familial tendency of these tumors has been noted. A common
      neuroectodermal origin is proposed as an explanation for the coexistence of the
      carotid body tumor and multiple endocrine tumors.

PMID- 10923312
TI  - [Anatomy of the valve system of the internal jugular vein].
AB  - BACKGROUND: Central venous catheters (CVC) in the internal jugular vein have
      become an important adjunct to the overall management of intensive care patients,
      but their use is associated with frequent neck complications. In a review of the
      literature anatomical variation in size, form and function of the valve system of
      the internal vein was found. PURPOSE: This study macroscopically and
      microscopically investigates the anatomical variety of the vein valves of the
      inferior internal jugular vein. MATERIAL AND METHODS: 100 cadavers from legal
      autopsies were investigated. We selected 45 patients with an acute myocardial
      infarction death and a control group (55 patients) formed by different causes of
      death. The veins were prepared for light microscopic study, the specimens were
      serially sectioned (ca. 30 sections) and stained with hematoxylin and eosin.
      RESULTS: Anatomical variety was observed predominantly unilateral on the right
      side of the internal jugular vein. The valves were often bicuspid at the right
      side (92%) and tricuspid on the left side (64%) and mostly located ca. 2 cm above
      the subclavia-jugularis bifurcation. In the histological study, a variability of
      the net of collagen and elastin fibres in the tunica intima and media was
      observed. The structure of the adventitia was constant. 18 patients with a
      jugular valve vein incompetence (age over 60) appeared to have thickening of the
      tuberculum in the sinus of the valve. The cups of the valves were found
      rudimentary in these patients with advanced stages of tricuspid incompetence.
      CONCLUSION: The present study demonstrates the variety of the valves of the
      jugular vein. They play an important role to impede the retrograde flow during
      cardiopulmonary resuscitation as well as in jugular vein cannulation.

PMID- 10923314
TI  - [GSTM1 gene polymorphism in patients with head and neck tumors].
AB  - BACKGROUND: Glutathione S-Transferase mu (GSTM) is a phase II detoxification
      enzyme, which rapidly detoxifies carcinogens found in tobacco smoke. The
      prevalence of this polymorphism is about 50% in the caucasian population. The
      lack of GSTM1 has been linked with an increased susceptibility of smoking related
      cancers. A homozygote deletion of the GSTM-gene results in a missing gene
      product. The objective of this study was to investigate the frequency of the
      GSTM1 null genotype in squamous cell carcinoma of head and neck, especially the
      larynx and hypopharynx and to analyse the occurrence with respect to certain
      anatomical sites of cancer. MATERIAL AND METHODS: The GSTM1 genotypes of 83
      patients with head and neck cancers and 60 healthy controls were determined by
      polymerase chain reaction (PCR) using blood leukocyte DNA. The presence or
      absence of the PCR-product after electrophoretic separation in an 2.0% agarose
      gel revealed the positive or negative genotype. RESULTS: The absence of the GSTM1
      gene (null genotype) was found in 64% of all head and neck cancer patients and in
      48% of the healthy controls (p < 0.05). Separating for cancer site, the null
      genotype was found in 44% of patients with hypopharyngeal cancer and in 78% of
      patients with laryngeal cancer (p < 0.05). The protein concentration of GSTM
      enzyme correlated with the genotype. CONCLUSIONS: The results suggest that GSTM1
      deficiency predisposes to head and neck cancer, especially to cancer of the
      larynx, which is particularly exposed to tobacco smoke carcinogens.

PMID- 10923316
TI  - [Oncology of the head and neck area].

PMID- 10923315
TI  - [Influence of comorbidity on the prognosis of squamous cell carcinoma in the head
      and neck].
AB  - BACKGROUND: The influence of comorbidity on the healing process and the prognosis
      of patients with carcinoma of the head and neck region undergoing surgical
      treatment is not clear. PATIENTS AND METHODS: In a retrospective study we
      examined the influence of coexistent diseases in 203 patients, hospitalized for
      curative surgical treatment. Findings on admission, supplemented by medical,
      anaesthesiological and neurological assessments, helped to form two subgroups:
      one of patients with minimal comorbidity (n = 135) and one with high comorbidity
      (n = 68). Subsequently the duration of hospitalization, incidence of
      complications, disease-free interval and survival was statistically compared.
      RESULTS: The duration of hospitalization, the incidence and degree of
      complications, the disease-free interval and the overall survival differed
      significantly, showing better results in the group with low comorbidity.
      CONCLUSION: Coexistent, mainly medical, diseases had a significant influence on
      the results of surgical treatment and prognosis of head and neck cancer.

PMID- 10923317
TI  - [Antibiotic therapy of head and neck infections. German Society of
      Otorhinolaryngology, Head and Neck Surgery].

PMID- 10923318
TI  - [The interesting case No. 35. Right pneumosinus frontalis dilatans].

PMID- 10923319
TI  - [Plastic reconstructions in the neck area. Superficial soft tissues of the neck:
      scar revisions].

PMID- 10923320
TI  - [Clinical factors associated with bone mass loss previous cardiac
      transplantation].
AB  - BACKGROUND: A high prevalence of osteoporosis has been described in patients
      before and after cardiac transplantation. But clinical factors involved in
      previous bone loss in this condition are not well known. The purpose has been to
      study bone mineral density (BMD) in patients subject to cardiac transplantation,
      analyzing clinical and biochemical factors related to bone mass in these
      patients. PATIENTS AND METHODS: We have studied lumbar and hip BMD in 51 patients
      candidates to cardiac transplantation, evaluating the functional grade of the
      cardiopathy, time of evolution of the disease, and antropometric and biochemical
      markers of bone turnover. BMD was measured using a dual X ray densitometer.
      RESULTS: A significant decrease in bone mass at lumbar and hip sites was found in
      patients with regard to normal population. A high prevalence of osteoporosis was
      found (27.4%). Time of evolution of the disease prior to transplantation was
      found to be the most important predictive variable in bone loss at trabecular
      bone (lumbar spine). No modifications were found in blood routine parameters,
      mineral studies and in serum intact PTH. Resorption bone markers were increased
      and formation markers were normal, suggesting a elevated turnover osteoporosis.
      Patients with osteoporosis had less BMI that patients without, indicating a
      protective effect of body mass. Patients with osteoporosis also had a greater
      time of evolution of the disease. CONCLUSIONS: There is a decreased bone mass in
      lumbar spine and hip and a higher prevalence of osteoporosis in patients with
      cardiac failure before cardiac transplantation. Time of waiting for cardiac
      transplantation has been an important factor found in the development of
      metabolic bone disease in these patients.

PMID- 10923321
TI  - [Norwalk virus-like food poisoning after eating oysters].
AB  - BACKGROUND: The aim of this study was to conduct a clinical-epidemiological and
      microbiological investigation into an outbreak of food-borne disease due to the
      consumption of oysters. PATIENTS AND METHODS: A historic cohort study was
      conducted into the consumption of 15 food items and clinical symptoms. The
      influence of each foodstuff was assessed by Mantel-Haenzel stratified relative
      risk (RRM-H) at 95% confidence intervals, and was confirmed by dose-response
      analysis with a chi 2 test tendency. We investigated sample stools from 5
      patients and 2 food-handlers. RESULTS: The overall attack rate was 38.0% (19/50).
      The median period of incubation was 39.0 h (maxim 62 and minimum 3 h). The
      symptoms were: fever 17.6% (3/17), diarrhoea 57.9% (11/19), vomits 84.2% (16/19),
      nausea 89.5% (17/19) and abdominal pain 89.5% (17/19). In stratified analysis,
      the Mantel-Haenzel method revealed a statistically risk for oysters (RRM-H = 3.3;
      IC 95%: 1.1-8.7), while the RRM-H value for sea snails was not significant (RRM-H
      = 2.8; IC 95%: 0.9-41.1). For oyster consumption, the dose-response test was
      statistically significant (p = 0.005). Examination by electron microscopy
      revealed small round structured viruses compatible with Norwalk-like virus. The
      oyster contamination was reported to the public health authority. CONCLUSIONS:
      This research highlights the usefulness of dose-response analysis in presenting
      epidemiological evidence, reveals the potential role of oyster consumption in
      food-borne disease such us Norwalk-like virus and show the need for monitoring
      production centres and oyster beds in order to prevent further cases of
      contamination.

PMID- 10923323
TI  - [Osteoporosis and transplantation of solid organs].

PMID- 10923322
TI  - [Application of molecular amplification methods in the diagnosis and follow-up of
      HIV-1 infection in children infected by vertical transmission].
AB  - BACKGROUND: To describe the vertical transmission of HIV-1 by means of molecular
      methods. PATIENTS AND METHODS: A prospective study between 1995 and 1998 of two
      groups of patients, A: 107 newborn infants to HIV-1 infected mothers, and B: 11
      infants with clinical suspicion of HIV infection, born to mothers who didn't know
      being infected. DNA and RNA PCR as well as reverse transcriptase gen mutations
      were tested. RESULTS: Eleven infected patients were identified, four from group A
      and seven from group B. Viral load at the moment of diagnosis was higher than
      100,000 copies/ml in all patients. Genotypic mutations of the studied codons were
      not detected in ten patients. CONCLUSION: Molecular amplification techniques are
      useful for early diagnosis and follow-up of HIV infection acquired by vertical
      transmission.

PMID- 10923324
TI  - [Treatment of type 1 Gaucher's disease. Still a long way to go].

PMID- 10923325
TI  - [Treatment of rheumatoid arthritis].

PMID- 10923326
TI  - [Fever, general malaise, abdominal pain, and diarrhea in a 63-year-old male with
      antecedents of polyarthritis, pleural effusion, polyadenopathy, atrioventricular
      block, and uveitis].

PMID- 10923327
TI  - [Tuberculosis and microbiologists].

PMID- 10923328
TI  - [Fluoxetine and convulsive crisis].

PMID- 10923329
TI  - [Edematous and pruriginous cutaneous lesion in the left forearm after a trip to
      Equatorial Guinea].

PMID- 10923330
TI  - [Pleuropericardial disorder in giant cell arteritis].

PMID- 10923331
TI  - [Comments about the case of the "66-year-old male with fever of 5 months of
      evolution"].

PMID- 10923332
TI  - [Need of vitamin D and calcium supplements in the population older than 65
      years].

PMID- 10923333
TI  - [Rheumatoid arthritis associated with microscopic polyangiitis].

PMID- 10923334
TI  - [Medical language again].

PMID- 10923335
TI  - Anterior neural tube malformations induced after all-trans retinoic acid
      administration in white rat embryos. I. Macroscopical observations.
AB  - For this study all-trans-retinoic acid was administered in pregnant white rats in
      their "prima gravida" pregnancy. Rats were divided in five groups. The first
      three groups were treated with 20 mg R.A./kg b.w. at several gestational days.
      The fourth group was treated with corn oil, while the fifth group remained
      untreated. All the animals were sacrificed during the first hours of the 21st
      gestational day. In the first group, three embryos, five absorptions and six
      compact embryonic masses were counted in litters. All the embryos presented
      exencephaly, combined with external anopthalmia. They also presented severe
      craniofacial malformations. In the second group, nine embryos and five compact
      embryonic masses were counted in litters. Three of the embryos presented
      exencephaly combined with external anopthalmia, while the six remaining presented
      complex craniofacial anomalies. In the third group, exencephaly was present in
      two embryos combined with anopthalmia, seven embryos had complex anomalies and
      four compact embryonic masses were counted in litters. Our results indicate the
      teratogenic involvement of all-trans-retinoic acid in anterior neural tube
      differentiation.

PMID- 10923336
TI  - All trans retinoic acid interfering with palatal development. Scanning electron
      microscopical and light microscopical observations on embryonic rat palate.
AB  - Diverse studies on retinoic acid teratogenesis, during the recent years, indicate
      that the drug's analogues target on diverse cell population during
      differentiation in mammals. During an extended teratological protocol concerning
      retinoic acid influence in diverse embryonic tissue differentiation in
      experimental animals we studied all-trans-retinoic acid's influence on palatal
      development in the white rat embryo. For this purpose, six groups of white rat
      embryos were studied: Group 1 was treated with 100 mg/kilogram of body weight
      (k.b.w.) on gestational days (g.d.) 10th and 11th, Group 2 was treated with 100
      mg all-trans-retinoic acid/k.b.w. on g.d. 11.5, Group 3 was treated with 50 mg
      all-trans retinoic acid/k.b.w. on g.d. 10th, 11th and 12th, Group 4 was treated
      with 50 mg all-trans-retinoic acid/k.b.w. on g.d. 11th and 12th, Group 5 was
      treated with 20 mg all-trans-retinoic acid/k.b.w. on g.d. 7.5, 8.5, 9.5, 10.5 and
      11.5, Group 6 remained untreated. Embryonic heads aged 20 days were observed by
      light microscopy and scanning electron microscopy. In all treated groups clefts
      and malformations concerning the differentiation of palatal cell populations were
      observed. All our findings were compared with normal palatal morphology of
      untreated "control" embryos. Among the malformations, median clefts were
      observed, extended along only a part of the primary and all the secondary palate
      for group 2, the primary and secondary palate for groups 1, 3 and 5 while on
      group 4, an irregularity of the median palatal raphe and rugae were combined with
      a median incomplete cleft extended between the primary and secondary palate. Our
      results are discussed in relation with the international literature results.

PMID- 10923337
TI  - [In vitro study of the effect of bisphosphonates on mineralization induced by a
      composite material: poly 2(hydroxyethyl) methacrylate coupled with alkaline
      phosphatase].
AB  - We have immobilized the mineralizing agent alkaline phosphatase (AlkP) in a
      hydrophilic polymer (poly 2(hydroxyethyl) methacrylate) (pHEMA) in a
      copolymerization technique. Histochemical study on polymer sections revealed that
      AlkP has retained its biological activity. The image analysis of sections using a
      tessellation method showed a lognormal distribution of the area of the tiles
      surrounding AlkP particles thus confirming a homogeneous distribution of the
      enzyme in the polymer. Pellets of pHEMA-AlkP were incubated with a synthetic body
      fluid containing organic phosphates (beta-glycerophosphate). Mineral deposits
      with a rounded shape (calcospherites) were obtained in about 17 days. We have
      investigated the effects of three bisphosphonates (etidronate, alendronate and
      tiludronate) on this system. Bisphosphonates at a concentration of 10(-2) M
      totally inhibited AlkP in solution at a concentration of 10(-4) mg/ml. Inhibition
      has been reported being due to the chelation of a metal cofactor (Zn2+).
      Etidronate and alendronate appeared to inhibit the calcospherite deposition onto
      the pHEMA-AlkP material in a similar way. Both bisphosphonates possess three
      sites for mineral complexion. On the other hand, tiludronate having only two
      sites was associated with a reduced inhibitory effect on mineralization. When
      used in microgravity conditions, mineralization was impaired with etidronate and
      larger crystals were obtained with tiludronate. However, these effects were
      obtained in non-physiological conditions (a 20 degrees C temperature was used
      during the STS80 flight of the space shuttle). The pHEMA-AlkP material provides
      an interesting method to study the effects of pharmacological compounds and
      environmental factors on the bone and cartilage mineralization process.

PMID- 10923338
TI  - [Anatomic variability and congenital anomalies of the gallbladder:
      ultrasonographic study of 1823 patients].
AB  - The authors report the results from the ultrasonographic exploration of the
      gallbladder performed on 1823 patients. They found morphologic variations and
      abnormalities in more than 33% of gallbladders, topographic ones in about 3.5% of
      observations and only 3 cases of real duplication of the gallbladder. Folds and
      septa may induce traps during echographic examination.

PMID- 10923339
TI  - [Determination, by in situ hybridization on interphasic nucleus, a cytogenetic
      DNA index; application to breast cancer; comparison of this DNA index to DNA
      indexes determined by imaging and flow cytometry].
AB  - In oncology, flow cytometry (FCM) and image cytometry (ICM) are commonly used to
      detect DNA aneuploid cell populations in solid tumors. Agreement between these
      two approaches is good. The use of both techniques in association minimizes the
      rate of FCM and ICM false negatives and gives better DNA pattern
      characterization, particularly for detection of any tumoral component in the FCM
      DNA diploid peak. Nevertheless, discrepancies exist between the FCM and the ICM
      DNA index values: the ICM DNA index is often greater than the FCM DNA index. The
      aim of the present study was to establish a cytogenetic DNA index by determining
      the chromosomal ploidy using a molecular cytogenetic approach and to compare it
      to the FCM and ICM DNA indexes. We present here the fluorescence in situ
      hybridization (FISH) technique we have adapted to the study of breast cancer in
      order to count the number of copies of the 22 + X human chromosomes in
      interphasic nuclei. This was achieved using a panel of 21 indirect FITC labeled
      probes which recognize specific chromosomic DNA sequences. Preliminary results
      obtained from DNA diploid and DNA aneuploid tumors are discussed.

PMID- 10923340
TI  - Educational programs in radiologic technology.
AB  - This article reports on a survey of educational programs in radiography, nuclear
      medicine, radiation therapy and sonography. The purpose of the survey was to help
      educators validate their individual program requirements by providing a profile
      of educational programs in each discipline. Survey results demonstrate
      similarities in program length, academic system, faculty teaching load and
      enrollment size. Major differences were found in clinical hour requirements and
      credit hour conversion.

PMID- 10923341
TI  - The importance of follow-up views in mammography.
AB  - Studies suggest that the aggressive use of follow-up mammograms could reduce
      reliance on breast biopsy as the definitive tool for ruling out malignancies.
      This article examines the value of various follow-up mammograms, including spot
      compression, magnification, 3- to 6-month follow-up, cancer follow-up and the
      annual mammogram. The roles of mammographers and radiologists in follow-up
      mammography also are discussed.

PMID- 10923342
TI  - Bone fracture fixation.
AB  - This article reviews the anatomy, physiology and biomechanics of bone and
      describes various types of fractures. It discusses the comparative advantages of
      different imaging techniques for fracture diagnosis and the radiographic
      characteristics of some common fractures. The article concludes with a
      description of fixation techniques and the role of imaging after treatment.

PMID- 10923343
TI  - Understanding advance directives.
AB  - The law recognizes individuals' right to bodily integrity and the right to refuse
      life-prolonging medical treatment. By means of an advance directive, individuals
      can protect their right to accept or refuse medical treatment, even after losing
      their ability to provide adequate legal consent. This article examines different
      types of advance directives, their efficacy and current controversies surrounding
      them. Nothing in this article is intended as legal advice and should not be taken
      as such. The information provided is not a replacement for the personalized legal
      advice readers might wish to obtain from their own attorney.

PMID- 10923344
TI  - Juvenile nasopharyngeal angiofibroma.

PMID- 10923345
TI  - Defining the educated professional.

PMID- 10923346
TI  - A case of fetus-in-fetu.

PMID- 10923347
TI  - New perspectives on acid-base balance.
AB  - This review will cover two main areas of acid-base balance, both of which are
      attended with much misconception and misunderstanding. One is the external
      balance of acids and alkali; the other is the contribution of bone buffering in
      acute and chronic metabolic acidosis.

PMID- 10923348
TI  - Influence of diet on acid-base balance.
AB  - It is well established that diet and certain food components have a clear impact
      on acid-base balance. For adults, the following factors are involved: 1) the
      chemical composition of foods (i.e., their content of protein, chloride,
      phosphorus, sodium, potassium, calcium, and magnesium), 2) the different
      intestinal absorption rates of the relevant nutrients, 3) the metabolic
      generation of sulfate from sulfur-containing amino acids, 4) the grade of
      dissociation of phosphorus at the physiologic pH of 7.4, and 5) the ionic valence
      of calcium and magnesium. All these factors allow us to estimate the potential
      renal acid load (PRAL) of any given food or diet. The PRAL (calculated for a 24
      hour period), together with a relatively constant daily amount of urinary
      excreted organic acids (in healthy subjects proportional to body surface area or
      body weight), yields the daily net acid excretion. This article provides an
      overview of the current concepts of diet influences on acid-base balance and also
      focuses on the underlying physiologic and biochemical basis as well as on
      relevant clinical implications.

PMID- 10923349
TI  - Twice-told tales of metabolic acidosis, glucocorticoids, and protein wasting:
      what do results from rats tell us about patients with kidney disease?
AB  - Much has been learned from animal studies in chronic renal failure that is
      germane to clinical studies because animal models parallel human responses. Such
      studies have affirmed that correction of metabolic acidosis has a favorable
      effect on protein metabolism, nitrogen balance and growth. In the presence of
      metabolic acidosis, catabolism is increased in uremia. Glucocorticoids are
      involved in accelerating protein degradation in muscle, which results in loss of
      lean body mass, while a low insulin level appears to play a permissive role in
      accelerating increased catabolism. Cellular mechanisms mediating these changes
      include upregulation of the ubiquitin-proteasome pathway and branched-chain
      ketoacid dehydrogenase enzyme activity in muscle. Many of these findings from rat
      studies have been confirmed in human studies and have important clinical
      implications because correction of metabolic acidosis improves nutritional status
      and blunts the associated increase in protein catabolism.

PMID- 10923350
TI  - Acidosis in chronic renal insufficiency.
AB  - In this article we deal with three aspects of acidosis in patients with chronic
      renal insufficiency: clinical characteristics, pathophysiology, and therapeutic
      approach.

PMID- 10923351
TI  - Acid-base balance in dialysis patients.
AB  - Acid-base balance in dialysis patients is achieved by a unique interaction
      between the patient and the particular mode of renal replacement therapy. The
      prevailing serum HCO3- in these patients is determined not only by endogenous
      acid production but also by the nature of the dialysis prescription and, in
      particular, by the bicarbonate (or lactate) concentration of the bath solution.
      Despite the technical advances in dialysis therapy, pre-dialysis serum HCO3-
      remains lower than normal in most patients receiving hemodialysis and in many
      patients receiving peritoneal dialysis. A central question is whether even a mild
      degree of acidosis increases morbidity and mortality in patients with end-stage
      renal disease. This article reviews the nature of the acid-base equilibrium
      achieved in patients receiving hemodialysis or peritoneal dialysis, addresses the
      question of whether correction of acidosis is beneficial, and reviews the
      techniques for increasing serum HCO3- in these patients. Based on the information
      available, it is clear that the patient with a serum HCO3- less than 19 mEq/L
      should be assessed to determine the cause of the low value and steps undertaken
      to correct the acidosis. Whether patients with steady-state values between 19 and
      24 mEq/L require specific attention remains an issue for further investigation.

PMID- 10923352
TI  - Acidosis and nutritional status in hemodialyzed patients. French Study Group for
      Nutrition in Dialysis.
AB  - In a cross-sectional study of more than 30% of French dialysis patients (N =
      7,123), we evaluated the relationships between predialysis plasma bicarbonate
      concentration and nutritional markers. Data including age, gender, cause of end
      stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels
      of midweek predialysis albumin, prealbumin, and bicarbonate were collected.
      Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and
      estimation of lean body mass (LBM) were computed from pre- and postbicarbonate
      dialysis urea and creatinine levels according to the classical formulas of
      Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6
      kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7
      +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32
      g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative
      correlation was observed between predialysis bicarbonate levels (within a range
      of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of
      variance using bicarbonate classes (p < 0.0001). Bicarbonate was also negatively
      correlated with albumin, prealbumin, BMI, and LBM. No relationship was noted
      between bicarbonate and Kt/V despite a positive correlation between Kt/V and
      nPCR. It is likely that a persistent acidosis observed despite standard
      bicarbonate dialysis was caused by a high dietary protein intake which results in
      an increased acid load, but also overcomes the usual catabolic effects of
      acidosis.

PMID- 10923353
TI  - What have isotope studies in humans told us about the nutritional effects of
      acidosis in dialysis?
AB  - In order to understand how acidosis might predispose to loss of lean body mass it
      is important to recognise that body protein is in a dynamic state with a daily
      turnover of approximately 300 g of protein in a 60 kg man. This is significantly
      greater than the daily protein intake at a level of 1 g.kg-1.day-1. Loss of lean
      body mass occurs when the balance between whole body protein synthesis and
      breakdown is negative. Measurement of whole body protein turnover is possible
      using either boluses or primed constant infusions of isotopically labelled amino
      acids. Previously, a variety of in vitro and in vivo animal studies have shown
      that acidosis increases protein degradation and amino acid oxidation. Several
      research groups including our own have used amino acid tracer techniques to
      examine whether protein degradation is increased in vivo in human subjects with
      acidosis and chronic renal failure. The results from these studies have shown a
      remarkable concordance with increased protein degradation in all groups of
      patients studied. However, the results for protein synthesis have been more
      difficult to interpret, with only a few studies directly measuring the effects of
      acidosis on amino acid incorporation into protein.

PMID- 10923354
TI  - A review of the effects of correction of acidosis on nutrition in dialysis
      patients.
AB  - Metabolic acidosis is a condition that is commonly encountered in both chronic
      renal failure (CRF) and in end-stage renal disease (ESRD). Known complications
      and surmised consequences associated with the acidosis of renal disease include
      bone lesions, depression of myocardial contractility, and growth retardation.
      Conversely the correction of acidosis in children with renal tubular acidosis
      improves growth velocity. This is also the case in children with CRF. The
      conclusion drawn from this study was that the correction of metabolic acidosis
      improved serum albumin concentrations in patients on hemodialysis and that this
      correction also induced a decrease in the nPCR.

PMID- 10923355
TI  - Use of different buffers in peritoneal dialysis.
AB  - A buffer is included in the peritoneal dialysis solution in order to offset the
      hydrogen ions normally produced during the metabolic processes. Nowadays, the
      buffer used is lactate, and its concentration in conventional peritoneal dialysis
      fluids is 35 or 40 mmol/L. Despite the general thought that peritoneal dialysis
      adequately corrects uremic acidosis, several studies have demonstrated that more
      than 50% of patients present mild to moderate acidosis with the solution
      containing 35 mmol/L of lactate, although with a 40 mmol/L solution this
      percentage decreases, a substantial number of patients still remain acidotic.
      This acid-base derangement is characterized by a normal pH and a below-normal
      plasma bicarbonate concentration, although the external body base balance is in
      equilibrium. There is evidence that this condition contributes to uremic
      osteodystrophy and has a detrimental effect on protein metabolism. Conventional
      solutions also affect mesothelial cell viability and local leukocyte function and
      have potential systemic effects such as the impairment of cellular redox state.
      New solutions containing pure bicarbonate or a mixture of bicarbonate and lactate
      have recently been investigated. A bicarbonate solution containing 34 mmol/L
      significantly increased plasma bicarbonate levels as compared with the lactate 35
      mmol/L solution. It has been demonstrated that bicarbonate solutions have better
      biocompatibility than the lactate buffered solution and substantially reduce
      abdominal discomfort experienced by a certain percentage of patients during the
      solution infusion. These studies demonstrated that the bicarbonate-buffered CAPD
      solution is safe, well-tolerated, and does not present any, even potential, side
      effects. Thus, it seems reasonable to consider the bicarbonate buffered solution
      the standard instead of the alternative, and it might entirely replace lactate as
      buffer in peritoneal dialysis fluid.

PMID- 10923356
TI  - Disturbances of acid-base balance and bone disease in end-stage renal disease.
AB  - Bone disease in patients with chronic renal failure (CRF) is thought to be the
      consequence primarily of the interplay of several factors, including the serum
      levels of parathyroid hormone (PTH), vitamin D, calcium, and phosphorus, and
      exposure to bone toxins such as aluminum or amyloid. Recently the metabolic
      acidosis noted with CRF has been implicated as an additional factor contributing
      to the genesis of bone disease. Although metabolic acidosis might be the dominant
      factor in the cause of bone disease in some instances, more commonly this acid
      base disturbance interacts with other factors contributing to the development of
      bone disease. The following article summarizes the data in support of an
      important role for metabolic acidosis in the genesis of bone disease in patients
      with CRF and presents our recommendations for treatment of uremic acidosis to
      prevent or treat the bone disease.

PMID- 10923357
TI  - [Guidelines by the German Society of Digestive and Metabolic Diseases for
      treatment of gallstones. German Society of Digestive and Metabolic Diseases].

PMID- 10923358
TI  - Activation of mitogen-activated protein kinases in different models of pancreatic
      acinar cell damage.
AB  - Mitogen-activated protein kinase (MAPK) family members, namely MAPK, c-Jun NH2
      terminal protein kinase (JNK), and p38MAPK, have been recently reported to have
      opposing effects on apoptosis. AIM: To determine the activity of MAPKs and the
      level of Bax, Bcl-2 and p53--proteins known to be involved in the regulation of
      apoptosis--in pancreatic acini subjected to stressful stimuli leading to cell
      death. METHODS AND RESULTS: Isolated pancreatic acini were irradiated for 30 min
      with ultraviolet B (UV-B) or stimulated with supraphysiological concentrations of
      cholecystokinin (CCK). As it was assessed by means of acridine orange/ethidium
      bromide staining, irradiation with UV-B induced predominantly apoptosis while
      necrosis predominated in CCK-stimulated acini. The activity of MAPK, JNK and
      p38MAPK was determined by means of Western-blotting, with the use of antibodies
      which recognize active, dually phosphorylated enzymes. Irradiation with UV-B
      induced a rapid, 3-fold increase in MAPK activity. It had a maximum at 30 min and
      then gradually declined to reach the normal level at 120 min. Concomitantly,
      early activation of p38-MAPK was found at 30 min. However, unlike MAPK, p38-MAPK
      activity was then gradually rising to reach a maximum (5-fold increase) at 180
      min. UV-B-induced activation of both kinases was not affected by the pretreatment
      with antioxidant--N-acetylo-L-cysteine or protein kinase C inhibitor--GF-109203X.
      In UV-B-irradiated cells, we did not detect any significant JNK activation as
      well as any significant changes in Bax, Bcl-2 and p53 levels assessed by means of
      Western-blotting. CONCLUSION: It seems likely that a specific interaction between
      MAPK and p38MAPK signaling pathway may be involved in the determination of the
      cell death mechanism in pancreatic acini subjected to stressful stimuli.

PMID- 10923359
TI  - Long-term outcome in patients with advanced hilar bile duct tumors undergoing
      palliative endoscopic or percutaneous drainage.
AB  - OBJECTIVE: Advanced tumors of the hepatic duct bifurcation (Klatskin tumors)
      present problems to the endoscopist in deciding which procedure to use for
      palliative treatment of the resulting cholestasis--endoscopic retrograde
      cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage
      (PTBD), or both. There are technical difficulties with all forms of treatment for
      stenoses in the hilar region and intrahepatic bile ducts, and there are as yet no
      clear data on which type of drainage is feasible or preferable. SUBJECTS: 59
      consecutive patients (30 men, 29 women; mean age 71 years) underwent palliative
      treatment for malignant hilar bile duct tumors of Bismuth stages II-IV during a
      three-year period (1992-94). METHOD: A retrospective analysis was carried out,
      and long-term follow-up data were obtained from telephone interviews with the
      patients, relatives, or referring physicians. RESULTS: The 59 patients were
      treated using ERCP (n = 20) or PTBD (n = 39). Three died within 30 days, and six
      were lost to follow-up. Clinically adequate drainage was achieved in 78% (n = 46)
      of the total patient group. Patient survival was a median of six months (range
      0.5-38), and was slightly longer when the primary drainage procedure was
      successful (7.5 months). Initial complications occurred in 11% after ERCP and in
      33% after PTBD, with a 30-day mortality of 5%. After the initial intervention,
      five patients who received ERCP treatment had to be switched to PTBD during the
      longer-term course. Three of these five patients died within 30 days of the PTBD
      insertion. CONCLUSIONS: Palliative treatment in patients with advanced Klatskin
      tumors is still suboptimal, even when combined endoscopic and percutaneous
      techniques are used in the same institution, allowing treatment to be tailored to
      the individual patient's needs. There is therefore a need for improvements in
      existing forms of treatment, as well as for the development of new forms of
      treatment.

PMID- 10923361
TI  - [Metastatic small intestine carcinoma--delayed diagnosis due to misinterpretation
      of diagnostic imaging and symptom confusion due to Bechterew disease and duodenal
      ulcer].
AB  - Misinterpretations of sonographic and computed tomography scans and reduced
      sensitivity to pain of a patient suffering from Bechterew's disease and duodenal
      ulcer caused delayed diagnosis of metastasized carcinoma of the small intestine.

PMID- 10923360
TI  - Synchronous herpes simplex virus and cytomegalovirus esophagitis.
AB  - Infective esophagitis is a rare disease, affecting mostly immunocompromised
      patients. Very few cases of a multiple viral infection have been reported. We
      present a case of combined cytomegalovirus (CMV) and herpes simplex virus (HSV)
      esophagitis in an 81-year-old female with extracapillary sclerosing
      glomerulonephritis treated for five months with steroids and chemotherapy. She
      died of septic shock. At autopsy, erosive and ulcerative esophagitis was found in
      the distal half of the esophagus. Slides were stained by HE, and the
      immunohistochemical avidin-biotin method was used to detect HSV and CMV
      infection. On histological examination of the esophagus, epithelial giant cells
      with intranuclear viral inclusions showing HSV immunopositivity were found at the
      margin of the ulcerations. Giant cells with intranuclear inclusions with CMV
      immunopositivity were also found in the mesenchymal cells obtained from the ulcer
      bed. Long-term immunosuppressive therapy provoked an immune deficiency, evidenced
      by grave leukopenia and depletion of all bone marrow elements. Diagnosis of HSV
      and CMV esophagitis is important to evaluate the risk of hemorrhage and
      esophageal perforation in esophagitis.

PMID- 10923362
TI  - Unusual negative side effects of non-steroidal anti-inflammatory drugs in the
      proximal colon.
AB  - Two cases of uncommon side effects of non-steroidal anti-inflammatory drugs
      (NSAID) are presented which show that in special cases NSAID lesions can be
      located predominantly in the proximal colon, that NSAID-caused lesions may
      present themselves as diaphragm-like strictures and that alterations by NSAID in
      this part of the bowel may bring enormous problems for the differential
      diagnosis.

PMID- 10923363
TI  - [Duodeno-ileal fistula development due to retroperitoneal lymph node metastases
      of sigmoid carcinoma].
AB  - We report on a 75-year-old patient suffering from persistent diarrhea with
      consecutive weight loss of 50 kg over a nine month period. Three years ago the
      patient had been operated on a sigmoid cancer. Ultrasonography and CT-scan
      revealed retroperitoneal masses due to lymph node metastases. Enteroclysis
      demonstrated a fistula between the duodenum and the terminal ileum. Whereas
      duodenocolic fistulae due to malignancies are well known to the best of our
      knowledge a fistula between retroperitoneal parts of the duodenum and the
      intraperitoneal intestine have not descripted so far.

PMID- 10923364
TI  - [Genetic hemochromatosis and the HFE gene: from molecular genetics to clinical
      diagnosis].
AB  - More than 90% of patients with genetic hemochromatosis carry a characteristic
      mutation in the HFE-gene (C282Y). HFE modulates the iron uptake by the
      transferrin receptor. Duodenal crypt cells of HFE-knockout mice show low
      intracellular iron concentrations which lead to an upregulation of the divalent
      metal transporter and enhanced iron uptake by duodenal enterocytes.
      Heterozygosity for the C282Y mutation appears to alter the course of other liver
      diseases like porphyria cutanea tarda and nonalcoholic steatohepatitis.

PMID- 10923365
TI  - [Probiotics for prevention of ulcerative colitis recurrence: alternative medicine
      added to standard treatment?].

PMID- 10923366
TI  - [New technologies in the daily lives of the elderly].

PMID- 10923367
TI  - [Technology in residences for support of a self-determined life style for the
      elderly. The research project "sentha" and initial results of a social science
      project].
AB  - Sentha is an interdisciplinary research team involving the Technical University
      Berlin, the Berlin Institute for Social Research GmbH (BIS), the German Centre
      for Research on Ageing at the University of Heidelberg (DZFA), the School of Fine
      Arts Berlin (HdK), and the Brandenburg Technical University Cottbus (BTU).
      Building on empirical investigations of the role of everyday household products
      in the everyday life of older people, product-independent design and assessment
      guidelines and new products are being developed in an intensive interdisciplinary
      process in order to better meet the needs of older people and to enhance their
      autonomous living. The following paper describes the contributions from the
      participating disciplines and presents initial results of the social sciences
      subproject, describing the problems arising in living independently in old age
      and detecting the demands on new technological solutions. Data are based on a
      representative survey conducted in 1999 and including a stratified sample of 1417
      men and women aged 55 and older.

PMID- 10923368
TI  - Acceptance and use of technological solutions by the elderly in the outdoor
      environment: findings from a European survey.
AB  - This article examines the use and acceptance of ticket machines, automatic teller
      machines (ATMs) and telephone cards by the elderly in four European regions. The
      analyses are based on data from an international project entitled "Keeping the
      Elderly Mobile", collected in Mannheim (former West Germany; N = 404 home
      dwelling respondents), Chemnitz (former East Germany; N = 400), Ancona (Italy; N
      = 600), and Jyvaskyla (Finland; N = 618). The random sample was stratified by age
      and gender in each country. Two generations of men and women (aged 55-74 and 75+
      years, respectively) participated in the study. Results show that respondents
      generally made little use of the three technologies under investigation: in fact,
      the majority of respondents does not use them at all. The most frequently used
      devices were ATMs in Chemnitz and ticket machines and telephone cards in
      Mannheim. On the basis of logistic regression analysis, age was the most
      important explanatory factor for the three technologies and for all four regions,
      i.e., the users were mostly the "young-old." Education was a more important
      variable than gender. In all four regions, the majority of the respondents who
      used the technologies assessed felt that each of them made life easier;
      nevertheless, ticket machines make life more difficult to almost every third user
      in Mannheim. Interesting differences and similarities among the towns were also
      found. The present study exhibits preliminary results regarding elderly and
      technology which future research should investigate in greater depth.

PMID- 10923369
TI  - [New vehicle technologies for supporting the mobility of the elderly].
AB  - Starting point for this analysis are the mobility needs and requirements of
      elderly, as well as problems concerning access and use of public transport.
      Elderly people as car drivers suffer from several performance deficits which are
      currently compensated by mobility restrictions and changed driving behaviour.
      Driver assistance systems, just available or soon on the market, are demonstrated
      and analysed with respect to their impact on elderly drivers. An expert
      evaluation comes to the conclusion that the most important systems for elderly
      are: emergency systems, enhanced vision systems and parking aids. Emergency
      systems can call rescue teams automatically or at driver's request, and direct
      them to the emergency location. Self imposed restrictions of elderly concerning
      night driving can partly be compensated by means of curve lightning and automatic
      dipping. Parking aids, using cameras or infrared technique are especially helpful
      for persons with moveability problems. The group of helpful, but not highly
      important driver assistance systems covers several means for longitudinal and
      lateral control of the car, comprising autonomous cruise control, antilock
      systems and electronic stability programmes. The value and impact of these
      systems are analysed in the light of risk homeostasis theory. Reduced work load
      and ease of mobility will at last result from user centered navigation systems,
      helping the elder driver also to move to new areas without orientational
      problems. The article demonstrates the particular importance of specific layouts
      of the man-machine-interface for elderly, to guarantee high acceptance and
      minimal distraction from traffic.

PMID- 10923370
TI  - [Possibilities and chances for using the internet by the elderly].
AB  - More and more older people interested in continuing education recognise the many
      possibilities for information, communication and co-operation which Internet
      offers to them. Institutes of continuing education and other institutions serving
      older people are required to provide training for this target group in order to
      make access to the world of the digital media easier, to support them in
      acquiring media competence and to design interesting virtual educational
      programmes and courses. In this article, the possibilities of showing people over
      50 the way to the new communication technologies will be described in view of the
      experiences gained during the information campaign "Senior-Info-Mobil". It will
      also be demonstrated based on the examples of the European network "Learning in
      Later Life" and other projects such as "Learning through Research" that virtual
      working groups and networks of elders can become a driving force of a new
      "learning culture", involving also those who do not live near universities or who
      for health and other personal reasons cannot participate in educational
      programmes offered in the area.

PMID- 10923371
TI  - [Telematics in geriatrics--potentials, problems and application experiences].
AB  - Modern telecommunication technology (telematics) has the potential to improve the
      quality of life for elders with physical and mental impairments as well as for
      their care giving relatives. Videophones, internet resources, and multimedia
      computers can be used for networking them together with social workers, nurse
      practitioners, physicians and therapeutic staff in service-centers. This can be
      viewed as a unique opportunity to establish and maintain instant and personalized
      access to various medical services in a situation where increasing needs are
      opposed to decreasing resources. However, it is not yet clear whether telematics
      is adequate, efficient, and effective in supporting care for geriatric patients.
      Some studies already showed its applicability and feasibility, but there are
      still no larger trials showing that maintenance or enhancement of autonomy can be
      achieved effectively by using new technologies. This article reviews the
      literature on telematics in geriatrics and presents data of a tele-rehabilitation
      project ("TeleReha", conducted at the Berlin Geriatric Center) which comprised
      mobility-impaired patients (N = 13, mean age 72 yrs), care giving relatives (N =
      8), and geriatric professionals. Networking was established using ISDN technology
      with videophones or PC-based videoconferencing systems. Results showed that
      participants regard telecommunication devices as a valuable resource for their
      informational and communicational needs. Use of telecommunication systems was
      inversely related to physical mobility. Having access to professional service and
      counselling was rated highly important but also the opportunity to establish
      reliable contacts with non-professionals (relatives, other participants). Despite
      experienced technical problems, use of telecommunication systems was evaluated
      more positively in the post-test as compared to the pre-test. In summary, current
      experience suggests that telematics can be used efficiently by geriatric patients
      and by relatives and professionals caring for them. However, evidence for a
      medically and economically effective use is still scarce. A lack of structural
      and organizational concepts for geriatric telematics initiatives can be
      identified which in part may be due to the fact that the considerable potentials
      of telematics applications are still largely unrecognized by geriatricians.

PMID- 10923372
TI  - [Variable perception of time in inpatient geriatric care--how long is the
      present?].
AB  - Time and again a lack of staff in the field of people's nursing is discussed
      (chronic lack of nursing staff); this means that there are not enough people to
      do the available work) (1). However, the time factor is also an important
      sociological dimension in old people's stationary care. First of all, this
      article points out the time dimension throughout life. This is followed by
      people's varying perceptions of the present and the related upsets and
      misunderstandings. Hereby the contradictory abundance and limitation in time as
      felt by the elderly also becomes apparent. The old people's awareness of the
      dwindling remainder of their own lifespans conflicts with the seemingly endless
      time of each day that passes.

PMID- 10923373
TI  - [Social status and life satisfaction of the elderly].
AB  - A rating instrument suited for a standardized evaluation of the social situation
      within a geriatric assessment is presented. The social dimensions "activities",
      "contacts", "living" and "finances" are screened by means of four to ten items
      and reflected by respective scores. The instrument was applied in a study group
      of 60 elderly persons of the general population and evaluated by means of life
      satisfaction measures. Positive correlations between the dimensions of the social
      situation and the respective domains of life satisfaction were found. Cut-offs,
      allowing the identification of patients, whose social situation is indicative for
      a low life satisfaction, are proposed.

PMID- 10923374
TI  - [Coping with stress by the elderly: a comparison of young, middle-aged and
      elderly couples].
AB  - The aim of this study was to investigate age effects on differences and
      similarities of individual and dyadic coping in 242 couples. There exist only a
      few systematically designed studies for age effects on individual coping. The
      majority of the results show that functional and dysfunctional individual coping
      are maintained constant if age differences are focused on. In our study we found
      high stability in the functional and dysfunctional individual coping over the
      three groups. By contrast, there are no studies except one for age effects on
      dyadic coping in the literature. Our results show differences in the positive
      emotional common dyadic coping and the total score of the positive common dyadic
      coping, both with the lowest values in the older couples.

PMID- 10923375
TI  - [Mechanisms of modification of excitatory and inhibitory inputs in various
      neurons of olivary-cerebellar network].
AB  - It is known from the experimental data that at different cerebellar neurons there
      are voltage-dependent Ca2+ channels, NMDA receptors, metabotropic glutamate and
      GABAB receptors. This receptor arrangement ensures that activation of excitatory
      and inhibitory input results in changes in activity of protein kinases and
      phosphatases and subsequent modification of synaptic efficacy. The mechanism of
      synaptic plasticity is advanced that in accordance with the known experimental
      data concerning the modification of excitatory and inhibitory inputs to Purkinje
      cells, granule cells, and deep cerebellar nuclei cells. The mechanism is based on
      a postulate that phosphorylation/dephosphorylation of AMPA (GABAA) receptors on
      cerebellar cells causes the LTP/LTD of excitatory (LTD/LTP of inhibitory)
      transmission. It is assumed that modification rules for Purkinje cells, granule
      cells, and deep cerebellar nuclei cells, wherein cGMP-dependent protein kinase G
      is involved in synaptic plasticity, are distinct from those of
      hippocampal/neocortical cells, wherein cAMP-dependent protein kinase A is
      involved in synaptic plasticity, since cGMP (cAMP) concentration decreases
      (increases) with Ca2+ rise.

PMID- 10923376
TI  - [Human temperament and choice preference between probability of the goal
      achievement and the goal value].
AB  - The purpose of this work was to experimentally ascertain the relationships
      between human formal-dynamic properties (temperament) and characteristics of
      his/her motivation sphere associated with the choice of a profession. Thirty
      eight students of a sports institute (aged 19-28) took part in the study. The
      formal-dynamic properties were assessed with the help of Rusalov's Questionnaire.
      The motivation of the choice of profession was assessed with the help of the
      specially developed test questionnaire. Two main components of choice motivation
      were identified: the value of the profession and probability of mastering this
      profession. It was found that persons of sanguine temperament (with a higher
      capacity for work, mobile and quick) are oriented primarily to the value of
      profession, while persons of melancholic temperament to the probability of
      mastering this profession.

PMID- 10923377
TI  - [Dependence of the verbal set on the cognitive activity context].
AB  - It was shown in adult healthy subjects (n = 60) that the set depends on the
      context of cognitive activity. Under conditions of its complication, when a
      subject had to solve successively several tasks, the stability of the verbal set
      markedly increased. This was expressed in a longer effect of "blindness"
      characteristic for the set to pseudo-word reading and increase in the time of
      reaction to a probe stimulus.

PMID- 10923378
TI  - [Relative meaning of lines and corners in geometric figures for their recognition
      by humans].
AB  - Neurons tuned to line-crossings (corners, crosses, Y-like and three-ray star-like
      figures) of different shape and orientation rather than to a single bar were
      found in the area 17 of the cat visual cortex. We studied the relative role of
      lines and corners of 2D and 3D geometrical figures for their recognition by
      humans. Probability of figure recognition during its tachistoscopic presentation
      was compared for the whole (control) and partly masked figures. Sides or corners
      of the figures were masked to varying degrees and probabilities of correct
      response were compared. The recognition probability successively decreases with
      increasing extent of figure masking. This decrease is significantly more
      pronounced for the figures without corners than for the figures without part of
      the lines. The relatively greater significance of the corners than sides of
      geometrical figures for human visual recognition and some possible neuronal
      mechanisms of this effect are discussed.

PMID- 10923379
TI  - [Simulation of the formula of emotions: subjective and objective quantitative
      indices].
AB  - Nonlinear dependence between the emotion intensity and main emotion components:
      the value of need and probability of its satisfaction is confirmed by the
      analysis of subjective and objective indices during mental reproduction of
      emotional situations. The dependence suggests a possibility of application of
      some its linear analogs in a certain range of changes in the intensity of need
      and possibility of its satisfaction.

PMID- 10923381
TI  - [Functional asymmetry of the neocortex electrical activity during food
      conditioning in dogs].
AB  - Four dogs were trained to perform a conditioned alimentary response to a sound
      stimulus. The EEG was recorded from six pairs of chronically implanted
      neocortical electrodes. The EEG spectra and coherence functions between the
      neighboring derivations of each of the hemispheres were analyzed in the theta,
      alpha, beta 1 and beta 2 frequency ranges. At the first stages of conditioning,
      the percent of cases increased when the highest mean values of EEG frequency were
      localized in the left hemisphere. Later on the percent of cases, when the mean
      coherence values in the left hemisphere were higher than in the right hemisphere,
      also increased. At the stage of conditioned response stabilization, this
      asymmetry either disappeared or the right hemisphere became more active than the
      left one. The spatial localization of the maximal values of the EEG frequency was
      different for different frequency ranges. The highest values in the beta 1 range
      were more frequently registered in the posterior cortical regions and in the beta
      2 range they were revealed, predominantly, in the anterior areas. The maximal
      values of coherence dominated in the anterior regions and their spatial
      distribution was similar for different frequencies. Thus, the initial stages of
      conditioning are accompanied by activation of the left hemisphere.

PMID- 10923380
TI  - [Deficit of learning of posture voluntary control in patients with cortical
      lesions of various locations: cortical mechanisms of posture regulation].
AB  - Forty two hemiparetic patients after cerebrovascular accidents were trained to
      change the position of the center of pressure according to a target on the screen
      with the visual feedback control. The learning was substantially impaired in
      comparison with the group of healthy subjects. Patients with the right
      hemispheric lesions showed somewhat greater learning deficit than patients with
      lesions in the left hemisphere. Lesion localization also affected the process of
      learning. The learning was disturbed to a greater extent in patients with lesions
      involving not only motor but also premotor and parietal cortical areas. In
      patients with parieto-temporal lesions the learning reached a very low level
      after three initial days of training, possibly, because of the deficit of sensory
      integration and of body scheme in the extra-personal space. Patients with
      combined lesions of the motor, premotor, and parietal areas showed the lowest
      results. The learning was shown to depend on the deficit of proprioception and
      extent of postural disturbances (asymmetry of body weight distribution and
      amplitude of the center of pressure oscillations) rather than on the extent of
      motor deficit (paresis and spasticity). However, the learning itself improved
      some motor disturbances.

PMID- 10923382
TI  - [Spatial organization of EEG in rats with genetically determined emotionality].
AB  - In order to study the possibility of EEG discrimination of genetically determined
      emotionality (increased propensity to emotional and stress reactions and anxiety)
      brain electrical activity was recorded in rats of two strains: Maudsley Reactive
      and Maudsley Nonreactive (24 derivations from the convexital skull surface were
      used). The program package "Synchro-EEG" was used for EEG processing. It was
      demonstrated that the two rat strains were significantly different in 120 EEG
      parameters of 840 ones analyzed. On the basis of 37 parameters, each rat was
      correctly recognized as belonging to the respective group with the error of
      4.89%. The analysis of the detected signs allowed their classification to be
      performed in accordance with the peculiarities of the emotional and cognitive
      processes and the level of nonspecific activation. Specific forms of interaction
      between these components in the system of emotional reactions were revealed.

PMID- 10923383
TI  - [Formation of lateralized motor skills in rats].
AB  - Adult Wistar rats were trained to get food with a forepaw from a narrow tube
      under conditions of free choice of a limb. It was shown that the presence or
      absence of limb preference determined by preliminary short-run testing far from
      always defines the character and extent of lateralization formed in the process
      of training. It was also found that reaching the maximal extent of lateralization
      requires, on average, more extended period of training for the animals, which
      finally constituted the group of right-handers, than for the rats finally
      classified as left-handers.

PMID- 10923384
TI  - [Conjugation of the neuronal impulse activity in the rabbit neocortex during self
      stimulation of the lateral hypothalamus].
AB  - Correlation of impulse activity of visual and sensorimotor neurons of both
      hemispheres in 10-s interval after self-stimulation of the right and left lateral
      hypothalamus was studied by plotting cross- and autocorrelation histograms. The
      number of cell pairs, in which sensorimotor neurons discharged after visual ones,
      increased after self-stimulation (from 24 +/- 6 to 44 +/- 7%). Frequencies of the
      alpha- and theta-range in crosscorrelograms increased; the alpha frequency
      increased mainly in the right hemisphere, while the theta frequency increased in
      the left hemisphere. The interhemispheric asymmetry in the interaction between
      cortical neurons was not associated with the side of hypothalamic stimulation.

PMID- 10923385
TI  - [Effect of sodium nitrite on the activity of the neocortex neurons during
      realization of defense and inhibition conditioned reflexes].
AB  - A decrease in intensity and duration of short-latency reaction components of the
      sensorimotor and visual cortical neurons to specific stimuli (pain reinforcement
      and light flashes, respectively) was observed after the administration of NO
      generating sodium nitrite (11 mg/kg, subcutaneously). Activation decrease in the
      visual cortex took place irrespective of biological significance of the light
      flashes, i.e., in case when this stimulus was a signal of defensive conditioning
      and in case when these flashes were applied with continuous light (a conditioned
      inhibitor). Sodium nitrite almost did not change the late activation of
      sensorimotor and visual neurons in response to pain reinforcement and
      disinhibitory action of the latter. The results confirm the viewpoint about
      different neurotransmitters in "specifically modal" and "non-specific" pathways
      to the neocortex during learning.

PMID- 10923387
TI  - [Neuronal activity in the prefrontal cortex in rats with various typological
      features during emotional affect].
AB  - Unit activity in the right and left prefrontal cortex was recorded in male Wistar
      rats after testing by the emotional resonance technique. Rats were divided in two
      groups by their reaction to the suffering cry of a partner. Rats from the group A
      ("altruists") escaped partner's crying, and those from the group E ("egoists")
      did not. Activity of neurons was analyzed in hungry rats, after feeding, during
      intracranial emotionally positive and negative stimulation, and during crying of
      the rat partner. Some differences in neural activity between A and E groups were
      revealed. In the hungry state the rate of neuronal discharges was higher in the A
      group. In both groups of animals the positive emotional stimulation was
      accompanied by more intensive neuronal reaction that the negative stimulation,
      but in the E group increase in the rate of neuronal discharges in both
      hemispheres was significantly more pronounced. Negative stimulation produced in
      both groups a significantly greater activation in the left hemisphere than in the
      right one while during the positive stimulation the neural activity was more
      intensive in the left hemisphere. The neuronal reaction to partner's crying was
      significantly higher in the A group in both hemispheres, while the neuronal
      activity in E group did not significantly change.

PMID- 10923386
TI  - [The role of muscarinic cholinoreceptors in the retrieval of the instrumental
      food conditioned reflex in cats].
AB  - It was demonstrated in cat experiments that impairment of the retrieval of
      appetitive instrumental conditioning observed after systemic administration of
      antagonists of muscarinic central cholinoreceptors scopolamine (a nonselective M1
      antagonist) and trihexyphenidyl (relatively selective M1 antagonist) could be
      connected with central and peripheral side effects of these antagonists. It was
      established that in case of the absence of side effects (low doses of
      trihexyphenidyl, 1 mg/kg) the blockade of M1-cholinoreceptors led either to
      selective fall-off of the motor instrumental reaction with in the presence of
      contextual behavior and other conditioned reactions or the appearance of errors
      that seemingly was indicative of the disturbance of triggering and realization of
      the motor program as the most important component of conditioning performance.
      The systemic injection of trihexyphenidyl (10 mg/kg), scopolamine (0.03 and 0.06
      mg/kg) and nonselective peripheral antagonist methylscopolamine (0.03 mg/kg) led
      to changes in the general functional state (disorders in the emotional and
      motivational sphere), the expression of which depended on the individual
      sensitivity to anticholinergic drugs. The disturbance of CR retrieval observed in
      parallel with side reactions was characterized by a complete cessation of
      conditioning and apparently was not associated with memory deterioration.

PMID- 10923388
TI  - [Modulation of the activity of monoaminergic brain systems and emotional
      condition by dalargin in rats during development of emotional resonance
      response].
AB  - Rats were divided in two groups by the reaction of emotional resonance (RER):
      with emotionally positive reactions (I, with fast RER acquisition, up to 100 s)
      and with emotionally negative reactions (II, with slow RER acquisition, more than
      200 s). After the RER acquisition, the activity of 5-hydroxitryptophan (5-HT)
      system of the I group of animals was lower than in the II group. The activity of
      noradrenaline (NA) and dopamine (DA) systems of the I group of animals was higher
      than in the II group. The between-group differences were enhanced by subcutaneous
      injection of dalargin. In some brain structures dalargin reversed these
      relations. These findings point to a complicated interpenetrating character of
      emotionally positive and emotionally negative states. Emotionally positive states
      include components of emotionally positive states, and emotionally negative
      states include components of emotionally positive states. Increase in 5-HT
      activity and decrease in activity of NA, DA, and opioid (OP) systems induce
      formation of emotionally negative states. Decrease in 5-HT activity and increase
      in activity of NA, DA, and OP systems induce formation of the emotionally
      positive state. It is suggested that 5-HT, NA, and DA systems play the central
      role in the processes of reinforcement, acquire the evaluative function, and are
      included in realization of all types of behaviors. OP is a primary modulator
      system which accompanies the unconditioned pain stimulus and connects it with
      systems of evaluative function.

PMID- 10923389
TI  - [Effect of deafferentation of the forelimb on the postnatal development of the
      synaptic plasticity in the hippocampus].
AB  - The postnatal development of LTP in CA1 area of hippocampus was studied in
      hippocampal slices from 13-20-day-old intact rats, after unilateral resection of
      n. medianus on the 13th day, and sham-operated animals. In slices from the intact
      rats prepared on the 15th-16th-day of postnatal development, the LTP magnitude
      and duration were significantly larger than in adult animals. Partial
      deafferentation eliminated this overshoot. However, a less pronounced increase in
      synaptic plasticity was observed in operated animals on the 17th day. The LTP
      suppression in the experimental animals may be explained by a decrease in the
      NMDA receptor activity due to enhanced synaptic activity in the hippocampus. We
      think that the limited sensory inflow from the partially deafferented forelimb to
      the hippocampus via the entorhinal cortex may be compensated by activation of
      other inputs from specific or/and nonspecific pathways. In contrast, the LTP
      magnitude and duration were significantly increased in slices from the sham
      operated rats. This increase may be explained by a decline of synaptic activation
      of the hippocampus under anesthesia.

PMID- 10923390
TI  - [Visual afferentation deficit during diffuse photosensitivity period in nestlings
      affects morphogenesis in Wulst neurons].
AB  - Golgi-stained preparations were processed with computerized morphometry to study
      the effect of the deprivation (eyes covered with nontransparent caps) on the
      development of neurons in the Wulst (the structure analogous to mammalian visual
      cortex) of pied flycatcher nestlings. Six-day-old nestlings that have only one
      form of the visual perception--diffuse photosensitivity--were studied. In the
      previous paper [Korneeva et al., 1994] in was shown that the Wulst of 6-day-old
      nestlings consisted of non-differentiated neurons and stellate-like cells at
      different stages of maturation; the latter group was subdivided into more- and
      less-mature cells. This work proved that even a 1.5-day-long deprivation (actual
      duration being counted off from the moment of appearance of the first retinal
      photoreceptors at the age of 4.5 days) resulted in significant changes in the
      geometry of stellate-like neurons. The changes in less-mature cells were
      predominantly destructive (decline of all quantitative indices of a cell,
      including the significant decrease in the total length of dendrites, maximal
      radius of the dendritic field and cell branching index), while the changes in
      more-mature cells were constructive (increase in all quantitative cell indices,
      including statistically significant increase in the soma section area, total
      length of dendrites, maximal radius of dendritic field and the number of foci of
      maximal branching). Different reactions of these cell types to the limitation of
      visual afferentation may be connected with differences in the afferent inflow to
      less- and more-mature cells or/and with different maturational stages of these
      neurons at the onset of deprivation.

PMID- 10923391
TI  - [History of the mainstream scientific research at the Institute of Higher Nervous
      Activity and Neurophysiology of the Russian Academy of Sciences].
AB  - The classical reflex theory of the higher nervous activity has been developed in
      the works of E.A. Asratyan, the first director of the Institute, and his
      scientific school. The novel aspects of the theory have been developed: the
      principle of system organization; the concept of the nervous center as a set of
      structures located in different areas of the central nervous system; conditioned
      switchover, the mechanism of conditioned connection closure; the origin and
      localization of conditioned inhibition; the two-way, forward and backward
      conditioned connections. The elaboration of physiological mechanisms of the
      active goal-directed motivated behavior was begun. V.S. Rusinov and his
      collaborates have developed the concept of the dominanta and role of the
      stationary excitation foci in the integrative brain activity. M.N. Livanov has
      created the concept of the spatio-temporal organization of bioelectric potential
      and systemic organization of brain activity. P.V. Simonov, beginning from 1964,
      has developed the need-informational theory of the human and animal higher
      nervous activity (behavior). As distinct from the theories that originate from a
      single viewpoint and reject all the others, Simonov's theory is integrative and
      follows the logic of development of brain science.

PMID- 10923392
TI  - [Neuronal and synaptic mechanisms of the conditioned reflex: systemic approach].

PMID- 10923394
TI  - [Nitric oxide and diseases].

PMID- 10923393
TI  - [Forward and backward conditioning].
AB  - A discussion. The evolution of the concept of the forward and backward
      conditioning is traced. An attempt to define more precisely the widely
      distributed term such as a "feedback", is made.

PMID- 10923395
TI  - [Some aspects of clinical use of nitric oxide in pulmonary hypertension].

PMID- 10923396
TI  - [Safety of nitric oxide inhalation technique].

PMID- 10923397
TI  - [Effect of prolonged inhalation of nitric oxide on chronically hypoxic rats].
AB  - OBJECTIVE: To explore the effect of prolonged nitric oxide (NO) inhalation on
      chronically hypoxic rats. METHODS: Male Wistar rats were randomly divided into 3
      groups: 1) room-air control (C); 2) hypoxia (H); 3) hypoxia with the inhalation
      of 20 ppm NO(2NH). RV/LV + S, mPAP and the histopathology of the lung were
      examined. Plasma levels of ET-1 and cGMP were detected by radioimmunoassay.
      RESULTS: 1. Hypoxia caused marked elevation in mPAP and RV/LV + s (both P < 0.001
      vs Group C). NO significantly reduced mPAP and RV/LV + S; 2. Hypoxia raised the
      percentage of intra-acinar muscular artery (MA) and lowered that of nonmuscular
      artery (NAM). MA decreased from 35.2% to 16.8% in Group 2NH; NMA increased from
      43.6% to 64.8% in Group 2NH, 3. The plasma level of ET-1 increased and that of
      cGMP droped significantly in Group H(both P < 0.001 vs Group C). NO resulted in a
      marked reduction in the plasma ET-1 and an increase in plasma cGMP; 4. Inhalation
      of NO had no effect on methemoglobin and lung index in hypoxic rats. CONCLUSIONS:
      Prolonged inhalation of 20 ppm NO can attenuate hypoxic pulmonary hypertension
      and inhibit the hypertrophy of the pulmonary vascular smooth muscle and the right
      ventricle NO, when inhalated at a concentration of 20 ppm for a long duration,
      will cause no toxicity in chronically hypoxic rats.

PMID- 10923398
TI  - [Effects of specific removal of circulating tumor necrosis factor-alpha by
      immunoadsorption on nitric oxide in endotoxin shock].
AB  - OBJECTIVES: To evaluate the effects of specific removal of circulating TNF-alpha
      by immunoadsorption on nitric oxide (NO) in endotoxin shock. METHODS:
      Immunoadsorbent against TNF-alpha was produced by the attachment of anti-TNF
      alpha monoclonal antibody (McAb) to agarose beads. Blank columns were made of
      agarose beads without the attachment of anti-TNF-alpha McAb. New Zealand white
      rabbits were injected intravenously with Lipopolysaccharide (LPS, Escherichia
      coli O111: B4, 8.0 x 10(9) cfu/kg. B.W), and then were randomly divided into
      three groups: (1) control group(n = 25); without other treatment. (2)
      pseudoperfusion group(n = 25): rabbits underwent hemoperfusion through the blank
      columns. (3) perfusion group (n = 15): rabbits underwent hemoperfusion through
      the immunoadsorbent columns. Hemoperfusion was started at 1 h after the injection
      of LPS, and was sustained for two hours with blood flow rate of 5 ml/min.
      RESULTS: Mean arterial pressure in the perfusion group was significantly
      increased at 30 min after hemoperfusion (P < 0.05). It maintained a level higher
      than that before hemoperfusion (P < 0.05), and was higher (P < 0.05) than that in
      the control and pseudoperfusion groups at 3 h (end of the monitoring period). The
      plasma TNF-alpha level in the perfusion group was significantly lower than that
      in the other two groups at 2, 3 and 6 hour after LPS injection (P < 0.05).
      Although the concentration of plasma nitrite (NO2-, one of the stable end
      products of NO) in the perfusion group was significantly lower (P < 0.05) than
      that in the other two groups from 3 h after LPS infusion, it was significantly
      higher (P < 0.05) than the baseline value from 30 min to 12 h. The activities of
      NO synthase (NOS) in the heart and lung were significantly lower (P < 0.05) in
      the perfusion group than in the other two groups at 24 h. The serum levels of
      alanine transaminase, aspartate transaminase, urea nitrogen, creatinine, lactate
      dehydrogenase, alpha-hydrobulyric dehydrogenase and alkaline phosphatase in the
      perfusion group were significantly lower (P < 0.05) than those in the other two
      groups at 24 h. Moreover, the survival rate of rabbits in the perfusion group was
      higher (P < 0.05) than that of the other two groups at 24 h. CONCLUSION: Specific
      removal of circulating TNF-alpha by immunoadsorption actually acts as the
      selective inhibition of the inducible NOS(iNOS) and may be a new and effective
      therapy for endotoxin shock.

PMID- 10923399
TI  - [The effects of nitric oxide synthase on secondary spinal cord injury: an
      experimental research].
AB  - OBJECTIVES: To investigate the effects of the changing amount of nitric oxide on
      secondary spinal cord injury and determine the role of nitric oxide during
      secondary spinal cord injury. METHODS: After close spinal cord modest injury (T9)
      by fluid-percussion model, rats were given saline, small dose of L-NAME (8 mg/kg)
      and large dose of L-NAME (40 mg/kg) respectively. The changes of hemodynamics,
      tissue constitution, and neural function were observed. RESULTS: We found small
      dose of L-NAME had little effects on the hemodynamics but could improve neural
      function. Whereas, large dose of L-NAME raised the MABP significantly,
      constricted pial arteriole (90 minutes, 10%), decreased regional spinal cord
      blood flow (SCBF) (90 minutes, 22%), augmented the dysfunction of neural system.
      Rats lost weight and the rate of death raised. CONCLUSIONS: These findings
      indicated that nitric oxide could have dual role during secondary spinal cord
      injury. Controlling local nitric oxide production suitably through changing the
      activity of nitric oxide synthase could improve tissue survival and benefit the
      recovery of neural function.

PMID- 10923400
TI  - [Changes of GABA immunoreactivity in aged rat cochlear nucleus].
AB  - OBJECTIVES: To detect the changes of gama-aminobutyric acid (GABA)
      immunoreactivity in the aged rat cochlear nucleus and to investigate its
      relationship with the initiation of presbycusis. METHODS: The cochlear nucleuses
      of adult (2-3 months) and aged (20-36 months) Wistar rats were stained with
      streptavidin/peroxidase (S-P) technique. GABA-positive neurons were counted with
      a computer-aid image analysis system. RESULTS: Most of the GABA-immunoreactive
      cell bodies were found in the superficial layers of the dorsal cochlear nucleus
      (DCN). The number of GABA-positive neurons decreased significantly in the DCN of
      the aged rat cochlear nucleus (P < 0.001). CONCLUSION: The reduction of GABA
      positive neurons in the aged rat cochlear nucleus may be related to presbycusis.

PMID- 10923401
TI  - [The construction and application of adenovirus vector coexpressing the
      heterodimer of human IL-12].
AB  - OBJECTIVE: To construct the recombinant adenovirus vector co-expressing the
      heterodimer of human interkeukin-12. METHODS: The full-length cDNA encoding human
      IL-12 subunits p40 or p35 was cloned by RT-PCR separately. The cDNA was ligated
      with encephalomyocarditis internal ribosome entry site (IRES), placed under the
      control of CMV promoter, and inserted into E1-substituted adenovirus vector
      pAx1cw to produce the bicistronic coexpression vector. Subsequently, the hIL-12
      recombinant adenovirus vector was cotransfected into 293 cells together with
      EcoT22I-digested Ad5 DNA-TPC, and the replication-deficient hIL-12 recombinant
      adenoviruses was generated efficiently by homologous recombination. RESULTS: The
      human IL-12 recombinant adenoviruses were obtained with the titers of 2.1 x 10(9)
      pfu/ml. 48 hours after the infection of the 293 cells, HepG2 cells and human
      primary skin fibroblasts with hIL-12 recombinant adenoviruses, the hIL-12
      expressions were detected by ELISA (30-50 ng/10(6) cells/24 h). The expressed hIL
      12 could stimulate the in vitro proliferation and IFN-gamma production of human
      PMNC. CONCLUSION: Prepared hIL-12 recombinant adenovirus vector can express
      biologically active hIL-12 and can be potentially used in cancer gene therapy.

PMID- 10923402
TI  - [Effect of recombinant human FLT3 ligand (rhFL) on in vitro expansion of human
      cord blood CD34+ cells].
AB  - OBJECTIVE: To determine the effects of recombinant human FLT3 ligand (rhFL) on in
      vitro expansion of human cord blood CD34+ cells. METHODS: Human cord blood CD34+
      cells were enriched by using a magnetic cell isolation system. CD34+ cells were
      incubated in liquid culture in the presence of different cytokines. The total
      number of all cells and the number of CD34+ cells and hematopoietic progenitor
      cells (CFU-GM and BFU-E) were counted at various time intervals. RESULTS: Human
      cord blood CD34+ cells could be enriched to the purity of more than 80%. The
      number of CD34+ cells increased 3.4 folds in the presence of rhFL + IL3 + IL6 +
      GMCSF + EPO in seven days, while in the control group without rhFL, it increased
      1.5 folds. The difference of the number of more matured hematopoietic progenitor
      cells in the CD34+ cell population between the control group and the rhFL group
      was not significant. CONCLUSION: Only the primitive hematopoietic progenitor
      cells are expanded by rhFL according to the results obtained in the exclusion
      method.

PMID- 10923404
TI  - [Evaluation of body surface ultrasonography in the diagnosis of diseases of
      abdominal segment esophagus and early-stage carcinoma].
AB  - OBJECTIVE: To investigate the possibility of detecting esophageal carcinoma and
      other lesions by body surface ultrasound (BSUS). METHODS: BSUS examinations of
      the abdominal segment of the esophagus in 797 subjects were undertaken. Wall
      thickness more than or equal to 6 mm, wall echo abnormality, and lumen
      morphologic changes were referred as the criteria of the disease. RESULTS: A
      visualization rate of 92% (n = 729) was obtained. 716 subjects without any
      esophageal diseases had a wall thickness of 4 mm or less; Of other 13, one
      patient had a wall thickness of 5 mm, 11 had 6 mm or more, and one had luminal
      cystic dilatation without wall thickening. In the 13 cases, the final
      pathological examination showed 5 cases of esophageal carcinoma (intramucosal,
      mucosal muscle, submucosal, proper musculature, and serosal patterns,
      respectively), 2 of metastatic lesion, one of leimyoma, 2 of edematous benign
      ulcer, one of diverticulum with polyp, and 2 of normal result. CONCLUSION: BSUS
      can not only detect the early-stage carcinoma, but also further demonstrate wall
      echo and pathologic changes inside and outside the wall. In the visualization of
      the submucosal tumor, it is advantage ous to barium examination and endoscopy.
      With its high sensitivity, simplicity, and non-intervention, BSUS can become a
      better screening method in everyday practice and in the area with high incidence
      of esophageal carcinoma.

PMID- 10923403
TI  - [Effect of the soluble immunocomplexes on the pathogenesis of hemorrhagic fever
      with renal syndrome].
AB  - OBJECTIVE: To determine the effect of the soluble immunocomplexes on the
      pathogenesis of hemorrhagic fever with renal syndrome (HFRS). METHODS: The
      soluble immunocomplex (IC) consisting of HFRS virus antigen and antibody was
      prepared previously in vitro, and was intravenously injected into BALB/c mice.
      The localization of IC in the tissues of mice was investigated by
      immunohistochemical method ABC. RESULTS: The results showed that 24 hours after
      injection, ICs were localized mostly in the blood vessels, such as the liver
      sinusoids, the splenic sinuses, the blood vessels of the mucosa and submucosa of
      the intestine, and the capillaries of the renal glomeruli, etc. 48 hours later or
      more, IC localized primarily on the parachymal cells, e.g., the hepatocytes, the
      epithelial cells of the renal tubules as well as some epithelial cells of the
      ducts and alveoli of some glands (submandular glands, pancreas). The cells
      degenerated in the areas with IC, especially in the hepatocytes and epithelial
      cells of renal tubules. These lesions were very similar to the pathological
      changes of the HFRS' patients, and were not found in patients injected with other
      IC. CONCLUSION: The soluble IC of HFRS can cause direct tissue injury in the
      HFRS.

PMID- 10923405
TI  - [Relationship between the risk factors of coronary artery disease and the
      severity of coronary artery lesions].
AB  - OBJECTIVE: To investigate the relationship between the risk factors of coronary
      artery disease and the severity of the coronary artery lesions. METHODS: A total
      of 446 consecutivey admitted patients were studied retrospectively. All patients
      suspected to have coronary artery disease and underwent a selective coronary
      angiography and a survey of risk factors during the hospitalization. RESULTS:
      Through Logistic regression analysis, advanced age, smoking, hyperlipidemia and
      course of diabetes mellitus were confirmed to be independent risk factors for
      coronary artery disease (OR = 1.02-1.23, P = 0.0406-0.0001). A significant
      correlation (F = 2.3130-19.2165, P = 0.1291-0.0001) between the severity of the
      coronary artery lesions and the age, the number of cigarettes in a day, the level
      of plasma lipids and the course of diabetes mellitus of the patients was found
      from the multiple regression analysis. CONCLUSIONS: Not only the development but
      also the severity of the coronary artery lesions is affected by the risk factors
      of advanced age, smoking, hyperlipidemia, and diabetes mellitus.

PMID- 10923406
TI  - [Treatment of avascular necrosis of femoral head by periosteal cell
      transplantation: an experimental study].
AB  - OBJECTIVE: To investigate the effect of periosteal cell transplantation on the
      repair of avascular necrosis of femoral head (ANFH). On the basis of successful
      culture of periosteal cells in vitro. METHODS: The tibial periostea of new born
      dog were excised and cultured under aseptic conditions. Eight adult dogs were
      used and divided into 2 groups: experimental group and control group. The animal
      model of ANFH was made by transferring the freed femoral head into the muscle
      under the ilium on one side in each dog. Two weeks after the establishment of
      ANFH, the cultured periosteal cells were collected and transplanted into the
      necrotic femoral heads in the experimental group, and the femoral heads without
      periosteal cell transplantation served as the control. Six weeks after cell
      transplantation, the femoral heads were taken out and histological examination
      was made. RESULTS: There was active bone formation in the experimental group. The
      new bone was arranged into bone trabeculae, most of which were covered by a
      monolayer of osteoblasts. Between bone trabeculae were fibrous tissue rich in
      blood vessels. In the control group, the bone trabeculae withered and remained
      necrotic. There were fibrous tissues with few blood vessels between bone
      trabeculae. CONCLUSION: Periosteal cell transplantation can improve the repair of
      ANFH.

PMID- 10923407
TI  - [An experimental study of the formation of osteoclast-like cell in rat bone
      marrow culture].
AB  - OBJECTIVES: To set up a culture method of osteoclast-like cell (OLC) formation in
      rat bone marrow and to investigate the effects of 1,25(OH)2D3 and osteoblasts on
      the formation of OLC. METHODS: The culture of bone marrow from 4-week old rats
      were studied for the formation of OLC. The culture was divided into four groups:
      group A, only bone marrow culture as control; group B, bone marrow and osteoblast
      (from the crania of newborn rats) coculture; group C, bone marrow culture with
      1,25(OH)2D3(final concentration 10(-8) mol/L); group D, bone marrow and
      osteoblast coculture with 1,25(OH)2D3. After 7 days of culture, the number of OLC
      which was recognized as tartrate resistant acid phosphatase (TRACP) (+)
      multinucleated cell, the cellular TRACP and the resorption pits on bone slice
      were examined. RESULTS: No OLC was present at the beginning of the bone marrow
      culture in any groups. OLC still failed to be detected in group A by the end of
      culture, and a few of OLCs could be found out in group B and C. The number of OLC
      in group D was more than that in the other groups (P < 0.01). The cellular TRACP
      in group A was lower than that in the other groups, and the cellular TRACP
      activity in group B and C was lower than that in group D (P < 0.01). In group D,
      several smaller resorption pits on The bone slice were observed. CONCLUSION: The
      formation of OLC requires 1,25(OH)2D3 and coculture with osteoblasts favors the
      formation of OLC in bone marrow culture.

PMID- 10923408
TI  - [Effects of Arg-Gly-Asp-Ser (RGDS) tetrapeptide on apoptosis-related genes in
      glomerular mesangial cells].
AB  - OBJECTIVE: To investigate the effects of Arg-Gly-Asp-Ser (RGDS) tetrapeptide on
      the expressions of apoptosis-related genes interleukin-1 beta-converting enzyme
      (ICE) and bcl-2 in human glomerular mesangial cells, so as to provide
      experimental evidence for regulating proliferation and apoptosis of mesangial
      cells with RGD-containing polypeptide. METHODS: Propidium iodide staining was
      used to observe the condensation and fragmentation of apoptotic nuclei. The
      internucleosomal DNA fragmentation was detected by DNA electrophoresis on agarose
      gel. The expressions of ICE and Bcl-2 were determined by reverse transcription
      polymerase chain reaction (RT-PCR). RESULTS: After ten hours of incubation, the
      glomerular mesangial cells treated with RGDS peptide displayed features
      consistent with apoptosis, such as nuclear condensation and fragmentation, and a
      regularly spaced "ladder" shape of genomic DNA electrophoresed. And RT-PCR showed
      that expressions of both ICE and Bcl-2 mRNAs were apparently increased in RGDS
      treated group, compared with that of the control group. CONCLUSION: These results
      demonstrated for the first time that RGDS peptide was able to induce apoptosis in
      human glomerular mesangial cells, during the process ICE and bcl-2 genes may have
      an important regulating role.

PMID- 10923409
TI  - [Polymorphism at the LDL receptor gene locus in patients with cholesterol
      gallstone disease].
AB  - OBJECTIVE: To investigate the association between the dinucleotide repeat
      polymorphism at the 3' end of the LDL receptor gene and cholesterol gallstone
      disease. METHODS: Polymorphism of the (dTA)n was amplified by using polymerase
      chain reaction, and the alleles identification was performed with denaturing
      polyacrylamide gel electrophoresis and silver stain technique. RESULTS: Analysis
      of allele frequencies in 131 unrelated Chinese gallstone patients and 79 controls
      indicated that the C allele was more frequent in the patients with cholesterol
      gallstones than that in the controls (0.40 vs 0.27, P < 0.01), and the frequency
      of the BB genotype of the LDL receptor gene was markedly lower (P < 0.005), while
      the CC and BC genotypes were significantly higher in the patients with
      cholesterol gallstones than in the controls respectively (P < 0.05, P < 0.05).
      CONCLUSION: The present study suggests that the LDL receptor gene polymorphism
      may be associated with cholesterol gallstone disease.

PMID- 10923410
TI  - [Perinatal maternal-infant transmission of human immunodeficiency virus and its
      prevention].

PMID- 10923411
TI  - [Current and future of male reproductive health in China].

PMID- 10923412
TI  - [Report of the first conference of national human productive health in China].

PMID- 10923413
TI  - [Study on gene of YRRM in azoospermia].
AB  - OBJECTIVE: To detect the abnormal YRRM gene in azoospermia and to explore the
      pattern of YRRM gene in Chinese men. METHODS: With the special primer for YRRM,
      the YRRM gene was analyzed using the PCR method. Extracting the testis total RNA,
      we performed the RT-PCR. The part of YRRM gene was sequenced. RESULTS: No
      amplification band of YRRM gene was noted in 4 of 74 Chinese men with azoospermia
      (5.4%). The YRRM gene was obviously expressed in the testis of man and showed a
      500 bp cDNA fragment. The cDNA and genomic DNA were different because the intron.
      We found that Chinese people only have YRRM1 pattern of gene, and the sequence of
      YRRM gene of Chinese men shows that the composition of the nucleotide is same as
      YRRM1 gene. CONCLUSION: These cases of abnormal YRRM gene may result in male
      infertility, YRRM gene and azoospermia is the YRRM1 gene is polymouphase of
      racial.

PMID- 10923414
TI  - [Effect of zinc deficiency on apoptosis of spermatogenic cells of rat tostis].
AB  - OBJECTIVE: To study the changes of testis apoptosis in zinc deficient rats will
      promote the understanding of the molecular mechanism of zinc deficiency in the
      development and function of testis. METHODS: 16 Wistar rats were divided randomly
      into zinc control group (ZC) and zinc deficiency group (ZD). The serum and testis
      zinc contents were measured with atomic absorse method; the apoptosis of
      spermatogenic cells was studied with in situ nick translation (ISNT) technique.
      RESULTS: Under zinc deficient status, the zinc contents of the serum and testis
      were obviously decreased (P < 0.05). The apoptosis number of spermatogenic cells
      was significantly increased (P < 0.01). CONCLUSION: The adequate amount of zinc
      is essential to the development of testis, whereas zinc deficiency can harmfully
      affect it. This effect is perhaps carried out in different ways, but the
      increasing apoptosis numbers of spermatogenic cells might be one of molecular
      miechanisms of the effect of zinc defficiency on testis development.

PMID- 10923415
TI  - [Immuno-epidemiological investigation of recurrent spontaneous abortion].
AB  - OBJECTIVE: To probe into immune pathogeny of recurrent spontaneous abortion
      (RSA). METHODS: Immunological analysis was made in ABO group antibodies by
      indirect hemagglutination, anti-zona pellucida antibodies by BA-ELISA, anti
      phospholipid antibodies by ELISA, blocking effect (MLR-BE) by blocking test one
      way mixed lymphocyte reaction, cytotoxic index (CI) by complement-dependent
      cytotoxic test, anti-idiotypic antibodies to blocking antibodies by MLR-BE
      inhibiting test, and effects of blocking antibodies on CD antigens by flow
      cytometry. In contrast to the healthy fertile women, 129 cases of primary
      abortion and 16 cases of secondary abortion were retrospectively analyzed for
      immunoetiological compositions. RESULTS: Among causes of RSA, lack of blocking
      antibodies accounted for 31.7%, anti-zona pellucida antibodies for 20.4%, anti
      phospholipid antibodies for 12.5%, and ABO group antibodies for 11.5%. Among
      causes of primary abortion, lack of blocking antibodies accounted for 31.4%, anti
      zona pellucida antibodies for 20.4%, anti-phospholipid antibodies for 8.5%, and
      ABO group antibodies for 8.4%. Among causes of secondary abortion, imbalance of
      idiotypic-antiidiotypic network of blocking antibody accounted for 39.4%, anti
      phospholipid antibodies for 31.4%, and ABO group antibodies for 22.4%.
      CONCLUSION: According to the above evaluation of immuno-epidemiology of RSA, RSA
      may be etiologically classified into lack of materno-fetal immuno-recognition,
      materno-fetal inappropriate immuno-recognition, and disorder of materno-fetal
      immuno-recognition.

PMID- 10923416
TI  - [Follicular fluid from patients with endometriosis decreases the binding of human
      sperm to zona pellucida in hemizona assay].
AB  - OBJECTIVE: To evaluate the effects of follicular fluid (FF) from women with
      endometriosis and tubal factor on sperm binding to zona pellucida under hemizona
      assay(HZA). METHODS: Follicular fluid was collected at IVF from patients with
      endometriosis and without endometriosis (tubal factor infertility). The HZA was
      used to study the effect of FF from patients with endometriosis and tubal factor
      on sperm binding to zona pellucida using media (EBSS/BSA) as control. RESULTS:
      The mean number of sperm binding to zona in endometriosis specimens and tubal
      factor infertility was significantly fewer than the number treated by culture
      medium (91 +/- 21 vs 239 +/- 35, P < 0.001; 109 +/- 22 vs 211 +/- 42, P < 0.005).
      The hemizona index was lower when the incubation was performed with FF from
      endometriosis patients compared with sperm incubated in FF from tubal factor
      patients (36 +/- 4 vs 54 +/- 4, P < 0.005). CONCLUSIONS: The inhibiting effect of
      FF from endometriosis patients is stronger than those without endometriosis. The
      follicular fluid of patients with endometriosis could contribute to infertility
      through impairment of gamete interaction.

PMID- 10923418
TI  - [The effect of nitric oxide administration on pateints with pulmonary
      hypertension: a dose-response study].
AB  - OBJECTIVE: To explore the dose-response relationship in patients with pulmonary
      hypertension after inhalation of nitric oxide (NO). METHODS: The effect of
      various concentrations (20, 40, 60 and 80 ppm) of NO on hemodynamics and cardiac
      function in 16 patients with pulmonary hypertension was studied with right heart
      catheterization. RESULTS: Pulmonary artery pressure and pulmonary vascular
      resistance reduced significantly after inhalation of various concentrations (20,
      40, 60 and 80 ppm) of NO. The vascular response to NO was not concentration
      dependant with a maximal effect obtained at 20 ppm. At inhalation of low dose of
      NO (20 ppm), the mean pulmonary artery pressure and pulmonary vascular resistance
      dropped by 26.5% and 40.3% (P < 0.0001), respectively. With the increase of
      inhaled NO concentration, pulmonary artery pressure and pulmonary vascular
      resistance did not decline. CONCLUSION: The best concentration of inhaled NO was
      not more than 20 ppm in the patients of this study.

PMID- 10923417
TI  - [Protective effect of selenium on human erythrocyte rheology].
AB  - OBJECTIVE: To assess the protective effect of selenium on RBC rheology during
      myocardial ischemia/reperfusion period in patients with VSD or ASD who underwent
      cardiopulmonary bypass. METHODS: The blood samples were taken from the coronary
      sinus, and ascorbyl free radical (A.), peroxidants (MDA), antiperoxidative
      activities (plasma SOD, erythrocyte GSH-Px), the membrane shear elastic module of
      RBC (mu), molecular rotational correlation times of lipids and proteins of RBC
      membrane (tau l, tau p) were measured and compared between control and selenium
      groups. RESULTS: After myocardial reperfusion only for one minute, in both groups
      A. was significantly increased (The increased percentage in the control group
      +68%, in the selenium group +66%), but the selenium group had lower MDA and GSH
      Px activity. On contrary to the control group with high A. level, A. of the
      selenium group was dropped about half since reperfusion for 5 minutes and
      recovered to the pre-ischemia level. After myocardial reperfusion, the control
      group had specific changes in membrane mu values as well as evidently prologed
      tau l and tau p. Simultaneously, except tau p at 5 minutes of reperfusion was
      obviously prolonged, no changes in the membrane mu and tau l were observed in the
      selenium group during the cardiac ischemia/reperfusion periol. CONCLUSION:
      Selenium can at least partly protect RBC rheology from free radical damage during
      the myocardial ischemia/reperfusion period.

PMID- 10923419
TI  - [Mismatched PCR combined with restriction fragment length polymorphism assay for
      identification of hot spot for mutation in core promoter sequence of hepatitis B
      virus in Chinese isolates].
AB  - OBJECTIVES: To investigate the prevalence of the core promoter variant in Chinese
      HBV carriers and to explore the clinical and epidemiological problems of the
      variant. METHODS: A novel method for detecting the double mutation in core
      promoter was developed. By using an antisense primer that starts at nt 1765 and
      bears a mismatch at nt 1767, we introduced an artificially created Bcl I cleavage
      site if the double mutation was present. The prevalence and clinical significance
      of mutation in the core promoter were investigated in 114 Chinese individuals
      infected with HBV. RESULTS: Serum samples from 37 asymptomatic carriers and
      patients harbored core promoter mutant, some with precore mutation. The
      prevalence was higher in carriers and patients without HBeAg than those with
      HBeAg. The results in the PCR-RFLP assay perfectly agreed with the data from
      direct sequencing. CONCLUSION: The presumed core promoter mutations resulting in
      decreased HBeAg synthesis might be one of the factors leading to persistence of
      HBV infection and active liver disease.

PMID- 10923420
TI  - [The association of sasceptibility of SLE and the gene polymorphism of TNF].
AB  - OBJECTIVE: To evaluate the association between the susceptibility of SLE and the
      gene polymorphism of TNF in Chinese Han population. METHODS: The single base
      change polymorphism in both TNF alpha gene and TNF beta gene were analyzed among
      SLE patients and normal controls by using PCR-SSCP and PCR-RFLP. RESULTS: No
      difference of gene or genotype frequencies of TNF alpha was noted in SLE patients
      and normal controls (P > 0.5), whereas TNF beta * 2 gene frequency increased
      significantly in SLE patients (SLE patients 65.7%, normal people 54.5%, P <
      0.05). CONCLUSION: TNF alpha gene polymorphism has no effect on SLE, but TNF beta
      * 2 allelic type may be related to the susceptibility of SLE in Chinese Han
      population to some extent.

PMID- 10923421
TI  - [Cloning and sequencing of E2/NS1 gene from a Chinese genotype III isolate of
      hepatitis C virus].
AB  - OBJECTIVE: To clone E2/NS1 gene from a Chinese genotype III isolate of hepatitis
      C virus into mammalian expression vector and analyze its primary nucleotide
      structure. METHODS: Reverse transcription nested-PCR methods were employed for
      amplification E2/NS1 gene which was cloned into mammalian expression vector
      pcDNA3 by directed clone. Sequence of inserted gene was analyzed by Sanger's
      method. RESULTS: E2/NS1 gene from a Chinese genotype III isolate of hepatitis C
      virus was cloned into eukaroytic expression vector effectively. Sequence of
      E2/NS1 showed 88.37% identity in nucleotide and 89.29% in putative amino acid to
      that of a Japanese genotype III isolate of hepatitis C virus. Nevertheless it
      showed 70.69% and 75.55% identity to that of a Chinese genotype II isolate of
      hepatitis C virus. CONCLUSION: E2/NS1 gene from a Chinese genotype III isolate of
      hepatitis C virus was successfully cloned into mammalian expression vector by
      technique of DNA recombination. Sequence analysis showed that E2/NS1 gene has
      good homology intra-genotype and poor homology intergenotype of hepatitis C
      virus. Research of primary nucleotide structure of different genotype hepatitis C
      virus might be helpful for the development of vaccine against the virus.

PMID- 10923422
TI  - [Renal aquaporin-2 water channel expression in congestive heart failure rat].
AB  - OBJECTIVE: To study aquaporin-2 (AQP2) that mediates vasopressin-regulated
      collecting duct water permeability. METHODS: Male Sprague-Dawley rats (200-250 g)
      underwent either a left coronary artery ligation, a model of CHF, or a
      shamoperation (Sham-Op). Five weeks after surgery, mean blood pressure (MBP) and
      cardiac output (CO) were measured by catheterization in the conscious animal. The
      rats were sacrificed 24 hours later. Left ventricular myocardial infarction size
      (LVMI) was estimated and the rats were divided into two groups according to the
      size of infarction. Total RNA and protein were extracted from whole kidney. AQP2
      and GAPDH mRNA were measured by Northern blot and AQP2 protein expression by
      Western blot. RESULTS: AQP2/GAPDH mRNA densities of Sham-Op, LVMI < 20% rats and
      LVMI > or = 20% rats were 1.385 +/- 0.023, 1.523 +/- 0.036, and 1.779 +/- 0.072
      (P < 0.01). AQP2 protein Western blot densities were 100% +/- 10%, 157% +/- 13%
      and 202% +/- 25% (P < 0.01). CONCLUSION: Both mRNA and protein of AQP2 gene
      expression are increased in CHF rat and this upregulation is present in the
      compensated (LVMI < 20% rats) and decompensated (LVMI > or = 20% rats) stage of
      CHF. This contributes to water retention associated with CHF.

PMID- 10923423
TI  - [National epidemiological study on obesity of children aged 0-7 years in China
      1996].
AB  - OBJECTIVE: To study on obesity of children aged 0-7 years in 11 cities in 1996.
      METHODS: The sampling size was 208, 513. The children were divided into 9 groups:
      birth-, 1 mo-, 6 mo-, 1 yr, 2 yr-, 3 yr, 4 yr-, 5 yr-, 6-7 yr. RESULTS: The
      prevalence of overweight was 4.2% (M4.2%, F4.2%); and of obesity, 2.0%(M2.2%
      F1.9%). The obesity to overweight ratio (ORR) was 2.1%(M1.9%, F2.2%). The
      adiposity rebound age (ARA) was 5 years. The adiposity rebound ratio (ARR) was
      3.2 for ARR1 (M2.9%, F.5%) and 2.0 for ARR2 (M1.7%, F2.4%) in obese children and
      3.5 for ARR1 (M 3.5, F3.5) and 2.5 for ARR2 (M2.8, F2.8) in overweight children
      respectively. The secular trend of prevalence of childhood obesity during 1986
      1996 showed that the prevalence of obesity increased annually at 9.1% (M10%,
      F8.7%). CONCLUSION: The obesity has already been a severe health and social
      problem of preschool children in China. The increment of prevalence of obesity
      during 1986-1996 has been out of control. The earlier of ARA and the larger of
      OOR is an important risk factor of increasing of obesity. 1 year and 5 years
      after birth, predicted by ARR, are two critical periods of obesity control in
      preschool children in China.

PMID- 10923424
TI  - [Community investigation of the activities of daily living (ADL) and medical
      conditions of the elderly in Shanghai].
AB  - OBJECTIVE: To study the ADL status and prevalence of medical conditions in aged
      population in Shanghai, and to analyze the impact of dementia syndrome and other
      illnesses to ADL performance. METHODS: Both the Chinese version of ADL scale
      (five items) and the list of self-reported illnesses questionnaire (32
      conditions) were used in the survey. After screening and case-identification,
      3745 noninstitutionalized aged residents, who were 65 years and older, were
      included in the analysis sample. A separate multiple logistic regression model
      was used in both groups (65-74 years and over-75), observing the effect of age,
      gender, education and medical conditions (as control variables) on ADL
      dependence. RESULTS: The prevalence rate of functional dependence in ADL was
      8.28%, and the prevalence curve was doubled steeply along with each ten years.
      The most prevalent medical conditions (> 20%) were hypertention, heart disease,
      cataract/glaucoma and artheritis/rheumatism, whereas, dementing disorder was
      4.61%. Of all illnesses, stroke, Parkinson's disease, dementia, diabetes and
      emphysema were the most important predictors of ADL dependence in both aged
      groups. In the group more than 75 years old, cancer, arteriosclerosis and
      hypertension seemed to be strongly related to ADL dependence, dementia syndrome
      was one of the remarkable risk factors. CONCLUSION: Dementing disorders such as
      Alzheimer's disease may lead to severe disturbance of ADL performance in the
      aged, therefore, the community rehabilitative measures and health care services
      should be stressed by the society to improve the quality of life of the elderly.

PMID- 10923425
TI  - [Diagnosis and endovascular treatment of multiple thrombosis in cerebral venous
      sinus].
AB  - OBJECTIVE: To study 12 cases of multiple thrombosis in cerebral venous sinuses
      and the diagnosis and endovascular therapy. METHOD: The long T2 and short T1
      signals in the related region of multiple venous sinuses on MR were important
      characteristics for the diagnosis before angiography. In the 12 cases, the
      treatment consisted of intermittent injection of urokinase via common carotid
      artery and oral administration of warfarin. RESULTS: Intracranial pressure of 11
      cases reduced to lower than 300 mm H2O and clinical deficits were markedly
      improved in 10 days. Re-angiography of 4 cases found partial recanalization in 2
      in one week after therapy. CONCLUSION: Intraoarterial thrombolysis combined with
      general anticoagulation in the treatment of multiple thrombosis in cerebral
      venous sinuses may be an effective meansure.

PMID- 10923426
TI  - [Comparison of Botox and a Chinese type a botulinum toxin in cervical dystonia].
AB  - OBJECTIVE: To confirm and compare the therapeutic efficacy of a Chinese type A
      botulinum toxin (CBTX-A, made by Lanzhou Biological Products Institute) and Botox
      (from Allergan Inc.) for cervical dystonia. METHODS: Prospective open study over
      3 years for cervical dystonia was analyzed. We treated 113 patients with
      medically intractable cervical dystonia in two groups during 1993-1996, 32
      patients with Botox and 81 with CBTX-A, with the age, durations and severity
      (Tsui's scale) matched. Some patients were injected under EMG guidance if
      necessary. The patients enrolled were followed up for 6-42 months. RESULTS:
      Considerable improvement of symptoms for the CD patients was observed with either
      Botox or CBTX-A. The Tsui scores showed a significant reduction after BTX-A
      injections. There were no significant differences in the clinical effects of two
      preparations, including the latency of response, maximal benefit, and duration of
      improvement. The patients' subjective assessments were similar. But the requested
      dose of Chinese preparation which produced the similar effects was statistically
      higher than that of Botox. Skin rash appeared within a few days after injections
      in 3 cases of CBTX-A group, but no one in Botox group. No statistical differences
      were noted in the other adverse reaction between them. CONCLUSION: The injections
      of two kinds of preparation both were simple and effective for the patients with
      cervical dystonia. Chinese preparation is a little less powerful but much cheaper
      than Botox.

PMID- 10923427
TI  - [Autologous endothelial cell transplantation in meacacos].
AB  - OBJECTIVE: To lay a theoretical foundation for the clinical application of
      autologous endothelial cell transplantation. METHODS: Macaco endothelial cells
      derived from superficial veins were cultivated in vitro for 13.89 +/- 1.36 days.
      The multiplied cells were lined in vitro onto the luminal surface of expanded
      polytetrafluoroethylene (ePTFE) grafts precoated with fibrin glue and
      fibronectin, then cultivated further for 9 days. 15 macacos were divided randomly
      into two groups. The common iliac arteries of the exper mental animals (n = 10)
      were replaced with endothelialized grafts, those of control (n = 5) with
      untreated ones. RESULTS: The amount of endothelial cells increased for 147.93 +/-
      88.68 folds. All the cells were diploid cells with a purity of 99%. The content
      of both 6-keto-PGF1a and vWF in the supernatant of primary and subcultured
      passages didn't have significant difference. Two hours and 9 days after cell
      seeding, the luminal surface of grafts were covered completely by a prominent,
      spindle-like endothelial monolayer underneath an even fibrin glue matrix could be
      seen. Nine days after seeding, the dense condensation of cytoskeleton on the
      luminal and basal side of cells increased apparently. Four weeks after grafts
      implantation 8/10 of experimental grafts, with a thickness of intima 80 +/- 12
      microns, were patent; while the 5 control grafts were occluded. CONCLUSION: The
      endothelial cell transplantation could effectively increase the patency rate of
      synthetic blood vessel prosthesis.

PMID- 10923429
TI  - [Current status of theoretical and practical study of myocardial protection].

PMID- 10923428
TI  - [Effects of erythropoietin or nitric oxide synthesis inhibitor on hyperdynamic
      circulatory state in cirrhotic rats].
AB  - OBJECTIVE: To observe the effects of erythropoietin or nitric oxide synthesis
      (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on hyperdynamic
      circulatory state in rats with cirrhosis. METHODS: Cirrhotic rat model was made.
      Cirrhotic rats were treated with NOS inhibitor L-NAME (0.5 mg.kg-1.d-1) by gavage
      or with erythropoietin (100 U/kg) injected subcutaneously for two weeks. The
      hemodynamic parameters in cirrhotic rats treated with L-NAME or with
      erythropoietin were determined by using 57Co-labled microsphere technique. Serum
      nitric oxide (NO) levels were also measured by using a fluorometric assay.
      RESULTS: Hyperdynamic circulatory state was observed in all rats with cirrhosis.
      Serum NO levels in cirrhotic rats were significantly higher than that in normal
      controls. Hyperdynamic circulation status in cirrhotic rats treated with
      erythropoietin or with L-NAME was markedly attenuated. As compared with untreated
      cirrhotic rats, serum NO concentration in erythropoietin-treated and L-NAME
      treated cirrhotic rats were significantly lower. CONCLUSION: L-NAME treatment
      could reverse the hyperdynamic circulatory state in cirrhotic rats which might be
      ameliorated by inactivation of overproduced NO by increasing hemoglobin with
      erythropoietin.

PMID- 10923430
TI  - [Epidemiology of Shiga-like-toxin producing infection in China and its prevention
      and control].

PMID- 10923431
TI  - [Myocardial ischemic reperfusion injury affected by the isozymes of nitric oxide
      synthase and their gene expression: experimental study].
AB  - OBJECTIVE: To study nitric oxide (NO), isozymes of NO synthase (NOS) and their
      gene expression in the isolated working rat heart after ischemia-reperfusion
      injury. METHODS: We quantified the gene expression of the isozymes of NOS by
      reverse transcription-polymerase chain reaction (RT-PCR), analyzed the myocardial
      NOS, malondialdehyde (MDA) content, NO, creatine phosphokinase (CPK) in effluent
      samples from coronary sinus, and measured the heart function before and after
      ischemia reperfusion. We also studied the effects of dexamethasone(Dex) and
      bradykinin(BK) introduced into cardioplegia on myocardial ischemia reperfusion
      injury. RESULTS: Our study demonstrated that the expression of constitutive
      NOS(cNOS) mRNA was downregulated and of inducible NOS(iNOS) mRNA upregulated with
      NO, cNOS decrease and iNOS increase during ischemia reperfusion injury. In Dex
      treated group, compared with the control group of ischemia reperfusion, the
      expression of iNOS mRNA was downregulated, NO and iNOS were reduced, the recovery
      of myocardial dysfunction was ameliorated and MDA, CPK reduced. In BK-treated
      group, the expression of NOS mRNA showed no significant change, NO and cNOS were
      increased. The recovery of myocardial dysfunction was ameliorated. MDA, CPK were
      also reduced. CONCLUSION: These results indicated that up- and down-regulation of
      expression of NOS isozymes could be one of the important mechanisms for
      myocardial ischemic reperfusion injury. Downregulating the expression of iNOS
      mRNA and activating cNOS could be helpful in myocardial protection.

PMID- 10923432
TI  - [Myocardioprotective effects of preconditioning in patients undergoing open heart
      operation].
AB  - OBJECTIVE: To investigate the myocardial protective effects of ischemic
      preconditioning (IP) on adult patients who undergoing prolonged open heart
      operation for complex heart diseases. METHODS: 30 patients were evenly divided
      into two groups at random. IP was elicited twice for 2 minutes ischemia from
      occlusion of vena cava and aorta followed by 3 minutes of reperfusion under
      cardiopulmonary bypass. Dynamic changes of ATP and purine metabolites in
      myocardium were measured. Electrocardiogram, leakage of myocardial enzymes,
      activities of SOD and LPO in serum and myocardial mechanics were investigated.
      RESULTS: IP reduced ATP repletion and maintained a higher ATP content in ischemic
      myocardium (P < 0.05 vs control group at 30, 60, and 90 minutes of ischemia).
      Reduced inosine content was found in IP group (P > 0.05). The inosine/adenosine
      ratio at 30, 60 and 90 minutes of ischemia was 4.2 vs 14.1, 17.6 vs 28.2, 29.2 vs
      71.3 for the IP and control groups, respectively, P < 0.05). There were also
      significant differences between the two groups in changes of ST-segment shifting,
      myocardial contractile and early postoperative recovery. CONCLUSIONS: IP can
      reduce ischemia-reperfusion injury on prolonged ischemic myocardium in humans
      even when combined with cold cardioplegia. Decreased inosine production and
      inosine/adenosine ratio in ischemic myocardium may be an important mechanism of
      IP, by which the production of oxygen free radicals are decreased during early
      reperfusion.

PMID- 10923433
TI  - [Crystalloid cardioplegia at different calcium concentration: its effect on
      immature rabbit myocardium].
AB  - OBJECTIVE: To determine the myocardial protective effect of St. Thomas II
      cardioplegia at different calcium concentration on immature myocardium. METHODS:
      Isolated perfused neonatal rabbit hearts from three groups (the calcium
      concentration of St. Thomas II cardioplegia was modified: [Ca2+] 0.6 mmol/L;
      [Ca2+]1.2 mmol/L; [Ca2+]2.4 mmol/L) were subjected to 20 degrees C hypothermia,
      90 minutes of global ischemia followed by 30 minutes reperfusion in Langendorff
      mode. RESULTS: Although the recovery of LVDP, +/- dp/dtmax at calcium content of
      2.4 mmol/L after 10 minutes of reperfusion was significantly higher than that at
      0.6 and 1.2 mmol/L calcium (P < 0.05, P < 0.01, respectively), the declined
      tendency of left ventricular hemodynamics in this group was detected after 20
      minutes of reperfusion. By the end of 30-minute reperfusion, the left ventricular
      hemodynamic recovery at 2.4 mmol/L calcium did not differ from those at 0.6
      mmol/L and 1.2 mmol/L calcium. Conversely, postischemic left ventricular
      functions at 0.6 and 1.2 mmol/L calcium were gradually improved during the 30
      minutes reperfusion. Ca(2+)-ATPase activity at 2.4 mmol/L calcium showed
      significant increase (P < 0.01, P < 0.001), whereas ATP content was lower than
      that of other groups. CONCLUSION: Calcium accumulated in extracellular space
      during ischemia enters myocardial cell via Ca2+ channel and Ca2+/Na+ exchange
      after reperfusion, activates Ca(2+)-ATPase, and finally accelerates
      adenosinetriphosphate (ATP) consumption induced by calcium, which would be
      responsible for the results of our study. We conclude that, from the point of
      view of myocardial cell energy metabolism, St. Thomas II cardioplegia at high
      calcium concentration can not provide immature myocardium with optimal myocardial
      protection.

PMID- 10923434
TI  - [The expression of proliferating cell nuclear antigen and alpha smooth muscle
      actin in papillary muscles of the patient with rheumatic heart disease and its
      significance].
AB  - OBJECTIVES: To reveal the change of chronic rheumatic cardiomyocyt phenotype and
      its relationship with myocardium fibrosis. METHODS: The papillary muscles samples
      were obtained from patients with rheumatic heart disease during mitral valve
      replacement. Normal papillary muscles samples obtained from adult and fetal heart
      during autopsy in control group. The specimens were examined using
      immunohistochemistry and immunoelectron microscopy observation with monoclonal
      antibody of antiproliferating cell nuclear antigen (PCNA) and anti-alpha smooth
      muscles actin (alpha-SMA), and imaging analysis was performed. RESULTS: The
      interstitial fibrosis (24.7% +/- 3.05%) and the ratio between inner and outer
      diamater of arteriolas (0.405 +/- 0.035) in rheumatic myocardium were higher
      significantly than those in normal myocardium. Immunohistochemical PCNA
      expression was not only in interstitial but also in hypertrophic cardiomyocytes
      of rheumatic heart disease. The positive expression in rheumatic myocardium
      increased. There were a lot of rough endoplasmic reticula, ribosomes and Golgi
      bodies in cytoplasm of PCNA and alpha-SMA positive cells. The degree of PCNA and
      alpha-SMA positive expression was increased with enlargement of fibrosis areas.
      CONCLUSIONS: There is not only a high expression of PCNA and alpha-SMA in the
      myocardium of patients with rheumatic heart disease but also in fetal myocardium.
      We suggested that pathological myocardial cells are constructive phenotype and
      synthetive phenotype. PCNA and alpha-SMA positive expression cells are in the
      proliferating stage, they take part in fibrotic progress and vascular
      reconstruction in the myocardium.

PMID- 10923435
TI  - [Hepatitis B virus infection and aflatoxin exposure in the development of primary
      liver cancer].
AB  - OBJECTIVE: To investigate the role of hepatitis B Virus (HBV) infection and
      aflatoxin (AF) exposure in the development of primary liver cancer (PLC).
      METHODS: A 10-year prospective case-control study was carried out in 737 HBsAg
      carriers and 699 HBsAg negative cases, and the aflatoxin B1 albumin adducts (AFB1
      Alb) were detected in the serum of the cohort including 30 HBsAg postive cases
      and 150 control individuals according to the case-control study model (ratio 1:5)
      at random in the high prevalance area of PLC. RESULTS: The average year-incidence
      rate was significantly higher in the HBsAg postive group (824.13/100,000) than in
      the control group (70.97/100,000, RR = 11.61). There was no significant
      difference in the incidence rate of other tumors between the two groups (P >
      0.05). The serum positive rate of AFB1-Alb was significantly higher in the PLC
      group (76.67%) than in the control group (48.67%, OR = 3.47), and the serum
      concentration of AFB1-Alb was also significantly higher in the PLC group than in
      the control group (P < 0.01). CONCLUSION: HBV infection and AF exposure are
      important etiological factors in the development of PLC and both result in
      carcinogenic synergy.

PMID- 10923436
TI  - [Gonadotropin releasing hormone and its receptor in the tissue of human
      hepatocellular carcinoma].
AB  - OBJECTIVE: To provide the basis for studying the relationship between
      gonadotropin releasing hormone(GnRH) and the regulation of hepatocarcinoma cell
      proliferation and differentiation, we observed the localization and distribution
      of GnRH and its receptor(GnRH-R) in various differentiated hepatocarcinoma
      tissues. METHODS: GnRH and its receptor were detected in 33 hepatocellular
      carcinoma(HCC) by immunohistochemical SABC technique. RESULTS: GnRH and its
      receptor had the same distributive pattern in hepatocarcinoma cells. The positive
      signal was found mainly on the surface and in the cytoplasm of hepatoma cells,
      with enhanced staining in the cytoplasm surrounding the nucleus; no positive
      signal was revealed in the nucleus. The GnRH positive rate (94%; 16/17) of
      edmondson grade I-II HCC was higher than that of grade III HCC (50%; 5/10) and
      grade IV HCC(17%; 1/6), (P < 0.05 and P < 0.001 respectively). In grades I-II HCC
      GnRH-R positive rate was 88% (15/17), which was higher than 17% (1/6) in grade IV
      HCC (P < 0.01). Although GnRH and GnRH-R positive rates in every grade HCC were
      lower than those in their related peri-cancerous tissues, the differences were
      not significant (P > 0.05). CONCLUSION: The expression of GnRH and GnRH-R in the
      tissues of hepatocarcinoma is related to their degree of differentiation.

PMID- 10923437
TI  - [Nitric oxide in the treatment of COPD-induced chronic cor pulmonale: therapeutic
      effect and mechanism].
AB  - OBJECTIVE: To study the hemodynamic and oxygen-dynamic effects and the mechanism
      of nitric oxide (NO) inhalation therapy in COPD-induced chronic cor pulmonale at
      acute exacerbation period. METHOD: Right heart catheterization was performed in
      11 cases of chronic cor pulmonale. The hemodynamic parameters and plasma
      endothelium-I(ET-I) level were examined and recorded before and after inhalation
      of 40 ppm NO for 20 minutes. The plasma level of NO and lipid peroxide Ca(2+)
      Mg(2+)-ATPase(calcium pump) and Na(+)-K(+)-ATPase (natrium pump) activities of
      RBC membrane in 30 cases of chronic cor pulmonale and 30 healthy controls were
      determined synchronously. RESULTS: After NO therapy, the average pulmonary
      pressure (PAPM) and pulmonary vascular resistance index (PVRI) were lowered by
      16.6% and 25.9% respectively (P < 0.05). Intrapulmonary shunt was lowered by
      16.3% (P < 0.05). ET-I also lowered and showed a positive correlation with PAPM
      (r = 0.59, P < 0.05). The activities of calcium and natrium pump were lowered
      when NO level declined, showing a positive correlation with NO concentration and
      negative correlation with lipid peroxides. CONCLUSION: No inhalation therapy
      exerted favorable hemodynamic and oxygen-dynamic effects on COPD-induced chronic
      cor pulmonale in its exacerbation period. Suppression of ET-I release might be
      one of the important factors for pulmonary vessel relaxation. Dysfunction of
      calcium and natrium pump activities in the acute exacerbation period of chronic
      cor pulmonale were closely related to NO level.

PMID- 10923438
TI  - [Apolipoprotein(a) and cortical cerebral infarction].
AB  - OBJECTIVE: To elucidate the correlation of apolipoprotein(a)[apo(a)] with
      cerebral infarction at the level of molecule and protein. METHODS: The serum
      Lp(a) level, by means of ELISA, the polymorphism of apo(a) protein, by SDS
      PAGE/Western blotting combined with silver staining assays, and the sequence
      polymorphism in 5' control region, the first exon and intron of apo(a) gene, by
      PCR-SSCP/AFLP assays, were detected in 85 healthy controls and 42 cases of
      cortical cerebral infarction. RESULTS: The serum Lp(a) level was remarkadly
      higher in the patients (153 +/- 3 mg/L) than that in the controls(56 +/- 4 mg/L)
      (t = 4.15, P < 0.001), even in the subjects with the same apo(a) phenotype. The
      allele frequency of low molecular weight phenotype containing B, S1 and S2
      isoforms was also significantly higher in the patients than that in the controls
      (0.5238 vs. 0.2941). There were 2 sites of sequence variance in the 5' control
      region of apo(a) gene in the studied population, which were of significant
      difference between the patients and controls, and were related to the variation
      of serum Lp(a) level. CONCLUSION: On the basis of proving further the risk of
      high serum Lp(a) level for AS event, we found that the low molecular weight
      phenotype of apo(a) is closely associated with cerebral infarction. The variation
      of serum Lp(a) level is also related to the sequence of apo(a) gene, indicating
      that both the size and sequence of apo(a) are associated with the susceptibility
      to cerebral infarction due to its impact on serum Lp(a) level.

PMID- 10923439
TI  - [P16 expression in lung cancer and its significance].
AB  - OBJECTIVE: To study the relationship of suppressor gene p16 and lung cancer for
      prognosis evaluation. METHODS: Immunohistochemical method was used to detect and
      analyse the expression of P16 protein of CDKN2 suppressor gene of 76 cases in
      formalin-fixed, paraffin-embedded tissue specimens of human lung cancer. RESULTS:
      P16 positive rate was 45%: 52% for 23 of 44 cases of squamous carcinoma and 29%
      for 7 of 24 cases of adenocarcinoma. Differentiation degree and prognosis of lung
      cancer were associated significantly with P16 expression. P16 expression was
      somewhat related to clinical stage. CONCLUSION: P16 gene plays a key role in the
      prognosis of patients with lung cancer.

PMID- 10923440
TI  - [Malignant clonogenic precursors in the peripheral blood of patients with
      multiple myeloma].
AB  - OBJECTIVE: To study the clonogenic potential of circulating malignant precursors
      in the peripheral blood of patients with multiple myeloma (MM). METHODS: A new
      cell culture system was used to expand putative malignant precursor clones and
      promote their differentiation. Meanwhile, immunocytochemical staining, Giemsa
      Wright staining and scanning electron microscopy were employed to reveal the
      growth properties and biological features of fresh and expanded malignant
      precursors and plasmacytes. RESULTS: Small lymphocyte-like B cells, which were
      actively proliferative and grew in the form of clusters, were found at the third
      day after culture. They accounted for 38% +/- 14%. The cells didn't express
      cytoplasmic immunoglobulin (CyIg) and CD38 antigen. In addition, no typical
      plasmacytes were observed. At the sixth day of culture, morphologically
      discernible plasmacytes, which grew in the form of large clumps in this culture
      system, were detected and represented 58% +/- 8%. These plasmacytes strongly
      expressed CD38 antigen and monoclonal CyIg identical to that of the original
      myeloma cells. CONCLUSION: Malignant clonogenic precursor cells, which have high
      proliferative potential, are present in the peripheral blood of MM cases, and
      could proliferate and differentiate into myeloma cells.

PMID- 10923441
TI  - [A cross-sectional study on HGV infection in a rural population].
AB  - OBJECTIVE: To determine the epidemiological characteristics and clinical
      significance of HGV infection, and to compare with HBV and HCV infections.
      METHODS: Anti-HGV, HBsAg, anti-HBs, anti-HBc and anti-HCV were detected by enzyme
      linked immunoassays (EIA). Anti-HGV positive sera were further tested for HGV RNA
      by a nested reverse transcription polymerase chain reaction (RT-nPCR). RESULTS:
      The anti-HGV prevalence rate was 12.9%. It was relatively low in children under
      10 years, and then increased with age and peaked in the group of 50-60 years of
      age (29.2%). The positive rate of HBsAg was 12.6%, and it quickly reached the
      highest (16.2%) in the 5-year old group. The prevalence rate of HBV infection was
      64.9%, and increased to a high level in the group of 10 years of age, and
      maintained high up to 79.2% in the 50 years old group. The HCV infection rate was
      15.3%. No anti-HCV positive cases were found in the group under 10 years of age.
      It was particularly high in the 20-40 years age group, and reached the peak in
      the group of 30 years old. No significant differences were found in the infection
      rates of HBV, HCV and HGV between male and female. HGV infection was associated
      with the history of blood donation, and the sexual transmission between couples.
      The anti-HGV positive rate of wives with anti-HGV positive husbands was 53.3%,
      significantly higher than that of those with anti-HGV negative husbands (7.8%).
      HGV coinfection with HBV or HCV had no influence on serum alanine
      aminotransferase (ALT). NO ALT elevation was found in the group with HGV
      infection alone. CONCLUSIONS: The epidemiological characteristics of HGV
      infection are different from those of HBV and HCV. HGV is transmitted by blood
      and sex, and does not seem to cause liver damage.

PMID- 10923443
TI  - [Nitric oxide inhalation in the treatment of acute respiratory distress
      syndrome].
AB  - OBJECTIVE: To investigate the role of nitric oxide (NO) in acute respiratory
      distress syndrome (ARDS). METHODS: Ten patients with ARDS underwent Swan-Ganz
      catheterization and mechanical ventilation. Before and after inhalation of 35
      ppmNO, hemodynamic, blood gas and DO2 parameters were examined. RESULTS: After
      inhaling NO, mPAP and PVR were significantly reduced from 3.6 +/- 0.6 kPa to 2.7
      +/- 0.5 kPa and from 32 +/- 11 kPa.s-1.L-1 to 22 +/- 9 kPa.s-1.L-1 respectively
      (P < 0.001). CO, BP and SVR were not significantly different (P > 0.05). Qs/Qt
      and P(A-a)O2 were decreased from 31% +/- 9% to 25% +/- 8% and from 37 +/- 6 kPa
      to 34 +/- 6 kPa respectively (P < 0.01). PaO2 and SaO2 were increased from 12 +/-
      3 kPa to 15 +/- 5 kPa and from 95% +/- 3% to 96% +/- 3% respectively (P < 0.05, P
      < 0.001). CONCLUSION: In the treatment of ARDS, inhalation of NO can have a
      better effect.

PMID- 10923442
TI  - [Thymectomy in the treatment of myasthenia gravis].
AB  - OBJECTIVES: To review the clinical course of patients with myasthenia gravis
      following thymectomy and to identify prognostic factors that may influence
      outcome. METHODS: We follow-up 91 patients with myasthenia gravis surgically
      treated with thymectomy through a median stereotomy from May, 1983 to October,
      1993. The overall 5-year remission and improvement probabilities were obtained by
      Kaplan-Meier Method. RESULTS: 36 (39.6%) patients showed remission, 27 (29.7%)
      improvement, 14 (15.4%) no change and 14 (15.4%) worsening. The overall 5-year
      remission and improvement probabilities of patients were 64% and 88%
      respectively. CONCLUSIONS: Most patient's symptoms after thymectomy were
      progressively improved with time, which is probably attributable to thymectomy,
      and the natural history of myasthenia gravis. Age at surgery, sex, duration of
      clinical course and pathological findings may be important prognostic factors for
      patients with myasthenia gravis after thymectomy.

PMID- 10923444
TI  - [Changes of airway responsiveness, and relative factors in asthmatics with
      remission at puberty].
AB  - OBJECTIVE: To study the airway responsiveness and relative factors in asthmatics
      with natural remission at puberty. METHOD: The airway responsiveness was
      evaluated by challenge of methacholine (PC20), blood sIL-2R, eosinophil count,
      basophil count and basophil releasability were detected in 18 asthmatics with
      remission at puberty (group I), in 20 asthmatics without remission at puberty
      (group II), and in 30 healthy controls (group III). RESULT: The mean value of
      PC20 in the group I was significantly lower than that of the group III (P <
      0.01), but still higher than that of the group II (P < 0.01). The blood sIL-2R
      and eosinophil values were droped almost to those of the group III, significantly
      lower than those of the group II. The basophil value and positive rate of human
      basophil degranulation test stimulated by mannitol with hyperosmolarity were
      still abnormal, significantly higher than those of the group III, and the
      basophil level was significantly related to the airway responsiveness.
      CONCLUSION: The asthmatics with remission at puberty have a certain degree of
      airway hyperresponsivenes that is related to the abnormal of basophil.

PMID- 10923445
TI  - [Association between ACE gene polymorphism and therapeutic responsiveness of ACEI
      in diabetic nephropathy].
AB  - OBJECTIVE: [corrected] To clarify the association between ACE gene polymorphism
      and therapeutic responsiveness of ACEI in diabetic nephropathy. METHOD: With the
      polymerase chain reaction technique, the angiotensin converting enzyme (ACE) gene
      insertion/deletion (I/D) polymorphism was studied in 31 NIDDM patients, 58 NIDDM
      patients with nephropathy, and 50 normal controls. RESULTS: There was no
      significant difference in the frequency of ACE genotypes among those NIDDM
      patients, NIDDM patients with nephropathy and nomal controls. Among 40 patients
      of DN group treated with ACE inhibitor(ACE-I), there was significant difference
      in genotype distribution between 19 efficacious cases and 21 nonefficacious
      cases: 8/2/9 vs 1/3/17 had DD/DI/II genotypes responsively (P < 0.01), DD
      genotype was best and II genotype was worst in therapeutic efficacy of ACE-I in
      NIDDM patients with nephropathy. CONCLUSION: The examination of ACE gene
      polymorphism is helpful for the diagnosis of the therapeutic efficacy of ACE-I in
      NIDDM with nephropathy.

PMID- 10923447
TI  - [The association of HLA-B27 binding peptide and spondylarthropathies].
AB  - OBJECTIVE: To explore the association of spondylarthropathies HAL-B27 binding
      peptide. METHODS: B27 molecules expressed on the B27-T2 mutant cell line do not
      have peptides. Such empty B27 molecules were not recognized by peptide-dependent
      monoclonal antibody, B27.M2. Positive B27.M2 reactivity resulted when B27-T2
      cells were incubated with peptide RRKAMFEDI derived from Chlamydia hsp60. THe
      importance of each residue in RRKAMFEDI was analysed by testing analogs in which
      each of the 9 residues in the peptide was consecutively substituted by 19 other
      amino acids. RESULTS: B27.M2 reactivity was the highest with arginine in second
      residue. The reactivities of residues other than arginine were less than 30% of
      the value with the parent peptide. CONCLUSION: The stringency for other residues
      was relatively low, indicating that immune recognition of B27-peptide complexes
      might have rather low stringency for peptide sequences. These peptide residues
      probably influenced antibody reactivity by inducing conformational changes.

PMID- 10923446
TI  - [Molecular cloning and sequencing of genes encoding MSP2 isolates strains from
      two of Plasmodium falciparum from Chinese patients with cerebral malaria].
AB  - OBJECTIVE: To provide the scientific evidence for designing safe and effective
      vaccines of human cerebral malaria. METHODS: Genomic DNA samples of two isolated
      Plasmodium falciparum isolate strains prepared directly from 5 cases of cerebral
      malaria patients' blood in mengla County, Yunnan Province (CMH/YN) and in
      Yingjiang County, Yunnan Province (CYJ/YN) were used for polymerase chain
      reaction (PCR) amplification and the two pairs of oligonucleotides for the highly
      conserved genes encoding FC27 merozoite surface protein 2 (MSP2) of Papua New
      Guinea strain of Plasmodium falciparum were used as primers. The PCR products
      were digested with BamH1 and Hind III respectively, and the generated fragment
      MSP2 were cloned into M13mp18 and M13mp19 vectors and their DNA was analyzed as
      the templates for DNA sequencing by the dideoxy chain-termination method.
      RESULTS: Compared with the published findings, FC27, K1, IC1 and CAMP sequences,
      DNA sequences of MSP2 from two isolated CMH/YN and CYJ/YN of Plasmodium
      falciparum strains from Chinese patients with cerebral malaria contained
      identical genes composed of 800 bp, encoding 264 amino acid, which were highly
      homologous up to 98.8% with that of FC27, K1 strain other than the IC1, CAMP
      strain. CONCLUSION: It is the first record of DNA sequencing of MSP2 determined
      from two isolated CMH/YN and CYJ/YN of Plasmodium falciparum strains from Chinese
      patients with cerebral malaria, MSP2 mutation may be one factor leading to the
      localized cerebral damage which causes clinical coma of human cerebral malaria.

PMID- 10923448
TI  - [The inhibitory effect of antisense phosphorothioate c-myc oligodeoxynucleotide
      on intimal hyperplasia in rat abdominal aortae after injury with a balloon
      catheter].
AB  - OBJECTIVE: To evaluate the effect of Antisense phosphorothioate c-myc
      oligodeoxynucleotide (ODN) on intimal hyperplasia in rat abdominal aortae induced
      by endothenial-denuded injury with a balloon catheter. METHODS: Antisense c-myc
      ODN was applied to the adventitia of injured abdominal aortae in rat introduced
      by pluronic gel releasing system and lipofectin delivery system. The animals were
      feeded with routine diet. Three weeks after intervention, the animals were killed
      and defined segments of arteries were sectioned and the histological sections
      were stained with elastic fiber staining. The cross-section of the artery was
      examined microscopically and the image was digitalized by image analysis system.
      The intima/media(I/M) area and I/M thickness ratios were calculated and analyzed
      statistically among groups. RESULTS: The intimal hyperplasia in antisense c-myc
      ODN-treated rats was inhibited significantly, demonstrated by microscopically and
      I/M area and thichness ratios, as compared with that treated with sense c-myc ODN
      and mismatch c-myc ODN. The larger dose of antisense c-myc ODN, the more obvious
      the suppression of intimal hyperplasia. CONCLUSION: The results suggest antisense
      c-myc ODN significantly suppressed the intimal hyperplasia in injured rat aortae
      in a sequence-specific fashion and dose-dependent manner. The investigation
      provides the basis for the early clinical trials assessing the therapeutic
      potential of antisense c-myc approach for the prevention of restenosis after
      angioplasty.

PMID- 10923449
TI  - [Effect of calcitonin gone-related peptide on coronary thrombosis and
      thrombolytic therapy].
AB  - OBJECTIVE: To inverstigate the effect of Caleitonin gene-related peptide (CGRP)
      on intracoronary thrombosis, thrombolysis, and reocclusion. METHODS: Thirty-six
      dogs were divided into three groups: saline solution (NS) group,
      nitroglycerin(NTG) group and CGRP group. The canine model of intracoronary
      thrombsis was established. Urokinase(UK) was administered intravenously. The time
      and rate of intracoronary thrombosis, patency and reocclusion were observed.
      RESULTS: The time of thrombus formation was markedly prolonged in the CGRP group.
      (NS 41 +/- 9 min, CGRP 72 +/- 11 min P < 0.01). The time of patency was shorted
      from 80 +/- 7 min(NS), 70 +/- 11 min(NTG) to 50 +/- 9 min(CGRP) (P < 0.01). The
      time of reocclusion was increased from 20 +/- 10 min(NS), 39 +/- 7 min(NTG) to 65
      +/- 12 min(CGRP)(P < 0.01). CONCLUSIONS: CGRP can delay the intracoronary
      thrombus formation, assist thrombolysis and decrease the reocclusis after
      thrombolysis.

PMID- 10923450
TI  - [Insulin-like growth factor system in human ovary and its actions].

PMID- 10923451
TI  - [The study of relation between Helicobacter pylori and gastrointestinal
      diseases].

PMID- 10923452
TI  - [The carcinogenetic and tumor-promoting effects of concentrated Helicobacter
      pylori culture supernatant in rats].
AB  - OBJECTIVE: To investigate the carcinogenetic and tumor-promoting effect of
      concentrated Helicobacter pylori culture supernatant (CHCS). METHODS: 0.25% and
      0.5% CHCS in drinking water administered orally for 52 weeks in rats, the changes
      of mucosal thickness, adherent mucosal mucus amount, DNA synthesis rate and
      precancerous lesions incidence in different times were examined, and the
      promoting effect of CHCS used in different periods on experimental carcinogenesis
      induced by MNNG was also clarified. RESULTS: Decreased mucosal thickness and
      amount of mucosal adherent mucus, increased DNA synthesis were found after CHCS
      feeding for 5 weeks in a dose- and time-dependent manner. By the end of the
      experiment at the 52nd week, the incidence of intestinal metaplasia(IM),
      sulfomucin positive IM and dysplasia in 0.5% CHCS group(57%, 39%, 18%
      respectively) were significantly higher than those in 0.25% CHCS group(28%, 10%,
      3% respectively) and control group(7%, 0%, 0% respectively). Whenever CHCS was
      used prior to, together with, or following MNNG administration, the incidences of
      gastric cancer and precancerous lesions were significantly increased in
      comparison with those in the rats treated with MNNG alone. CONCLUSION: Hp
      cytotoxin(s) may have direct carcinogenetic and tumor-promoting effects.

PMID- 10923453
TI  - [The relationship between Helicobacter pylori and expression of c-met oncogene in
      gastric precancerous lesions].
AB  - OBJECTIVES: To determine whether there is a relationship between the presence of
      H. pylori and alteration of c-met oncogene and to estimate the role of H. pylori
      in the development of gastric carcinoma. METHODS: 110 patients with
      histopathologically proven chronic gastritis were studied. We demonstrated
      expression and overexpression rates of c-met oncogene by using
      immunohistochemical staining. RESULTS: For chronic superficial gastritis, chronic
      atrophic gastritis, intestinal mataplasia and dysplasia, the expression rates
      were 22.2%, 44.1%, 67.5% and 61.9%. The overexpression rates were 5.5%, 26.4%,
      37.8% and 38.1% respectively. The positive rates of c-met oncogene protein were
      high among patients infected with H. pylori than those with no H. pylori
      infection (63% vs 32%). In the precancerous lesions of cellular atrophy,
      intestinal mataplasia and dysplasia, the expression rates of H. pylori positive
      patients were higher (68.9%) than those of H. pylori negative patients (30.5%) (P
      < 0.05). CONCLUSIONS: H. pylori is involved in the expression of c-met oncogene.

PMID- 10923454
TI  - [Biological diagnostic and therapeutic study on the infection of Helicobacter
      heilmannii].
AB  - OBJECTIVE: To study the epidemiology, microbiology, pathogenicity, diagnosis and
      therapy of Helicobacter heilmannii (Hh) infection. METHODS: Morphological
      methods, such as Gram staining of gastroscopic biopsy smears, Giemsa staining of
      histological slides and scanning electromicroscopy(SEM), and biochemistry
      techniques such as urease test(CLO), 14C urea breath test(UBT) were used to
      identify Hh infection in natural populations. The 16S rRNA gene of 4 strains of
      Hh were amplified, sequenced and analysed, using bacterial universal and
      Helicobacter genus-specific primers. RESULTS: Twenty cases of Hh infection were
      found in 992 peoples with the positive rate of 2.0%. There existed the phenomena
      of intrafamily cluster of Hh infection. 14 case of the gastic tissues were CLO
      positive and 3 cases of these patients were UBT positive, the bacterium cannot be
      isolated in vitro. Sporadic invasion of lymphocyte/plasmic cell were found in
      gastric mucosa with Hh infection. Formation of lymph follicles and invasion of
      neutrophlic cell could be found too. The "old triple therapy" regimen could
      eradicate Hh easily. The homology of 16S rRNA gene among 4 strains was between
      98.7%-99.7%, and can not be devided into two subtypes. The homology between Hh
      and H. felis or Hp were 95.6%-96.5% and 96.4%-97.1%, respectively. CONCLUSION:
      The prevalence of Hh in southern China is higher than that reported abroad. There
      may exist animal to person and person to person transmission mechanisms. Hh
      should be a new Helicobacter with lower activity of urease and weaker
      pathogenicity when compared with H. pylori. The infection of Hh is easy to
      eradicate through drug therapy.

PMID- 10923455
TI  - [Development of mouse and rat model of Helicobacter pylori infection].
AB  - OBJECTIVE: To develop different rodent model of H. pylori infection as to meet
      different requirement for different purpose of study. METHODS: 40 two-grade
      Wistar rats, 40 two-grade C57BL/6 mice and 40 SPF BALB/c mice were randomly
      divided into two groups: experimental and control groups. Animals in the
      experimental group were inoculated orally Hp strain (Sydney Strain 1, SS1), 0.4
      ml of inoculum per mouse, 1.5 ml per rat (10(9) organisms/ml) five times for a
      week. In 4, 8, 12 and 24 weeks after the last bacteria inoculum, 5 animals in the
      experimental and control groups were sacrificed respectively. Histology and Hp
      colonization were assessed by HE staining, Gimesa staining, Urease test, and Hp
      culture. RESULTS: In 4 weeks, in all experimental animals bacteria were clearly
      visible at antrum and body, but the number of Hp colonization varied according to
      the animal strain. Heavy colonization was seen in C57BL/6 in antrum and body, and
      in BALB/c and Wistar colonization was located mainly at antrum, less at body,
      which tended to increase over the experiment time, especially in Wistar. Hp was
      negative in the controls. All animals had no inflammatory changes in 4 weeks,
      however, in 8, 12 and 24 weeks in Balb/c. Wistar and C57BL/6 of the experimental
      group, mild to moderate chronic active gastritis was observed in antrum and body,
      which increased in severity over time, atrophy gastritis was still not seen in 24
      weeks. In contrast, in the controls, no remarkable changes were detected.
      CONCLUSIONS: SS1 Hp can colonize in the glandular stomach mucosa of BALB/c,
      C57BL/6 mice and Wistar rats and leads to chronic active gastritis in long-term
      study. SS1 mouse and rat model is adaptable for animal experimentation of H.
      pylori including vaccine studies, screening for novel therapeutics and
      investigation of mechanisms of pathogenesis.

PMID- 10923456
TI  - [Dynamics of anti-HEV ORF2, ORF3, IgM and IgG in serial sera of patients with
      hepatitis E and their clinical significance].
AB  - OBJECTIVE: To study the dynamics of anti-HEV ORF2, ORF3, IgM and IgG in serial
      sera of patients with hepatitis E. METHODS: Anti-HEV was detected in serial sera
      of 52 patients, by an enzyme-linked immunosorbent assay (EIA) based on two
      synthetic peptides separated or combined from open reading frame (ORF) 2 and 3 of
      HEV genome. RESULTS: Both anti-ORF2 and anti-ORF3 in serum were at the highest
      levels in early acute phase of the disease, and declined gradually with the
      course, especially anti-ORF3. The sensitivity of the EIA using both ORF2 and ORF3
      peptides was higher than that of either alone. The positive rates of anti-HEV IgM
      and anti-HEV IgG were separately 71.1% (32/45) and 97.8% (44/45) within 15 days
      after onset, then decreased more dramatically in IgM than in IgG with the course.
      CONCLUSION: Both ORF2 and ORF3 proteins should be used for the development of
      anti-HEV EIA kit. It seems to be more specific in anti-HEV IgM and more sensitive
      in anti-HEV IgG as a diagnostic marker of hepatitis E.

PMID- 10923457
TI  - [Hoffmann reflex elicited by magnetic stimulation of S1 nerve roots in the
      diagnosis of diabetic radiculopathy].
AB  - OBJECTIVE: To determine the incidence of radiculopathy in diabetic patients
      neurophysiologically. METHODS: The H-reflexes were elicited by magnetic
      stimulation to S1 nerve root at the first sacral foramen (S1 H-reflex) in 40
      normal subjects and 41 diabetic patients. The action potentials of the H-reflex
      were recorded from the soleus muscle. For comparison, a popliteal H-reflex
      (stimulated at popliteal fossa), and a regular distal sensory and motor
      conduction of the tibial nerves were simultaneously evaluated. RESULTS: A
      significant correlation of the peak interval of H wave and M wave (HMI) of the S1
      H-reflex with body height and age was confirmed by multiple regression analysis
      in the normal subjects. The simultaneous regression of the HMI adjusted on age
      and body height produced the formula as 0.02 x (age) + 0.03 x (height) + 0.92. At
      95% normal limits of the significant test, 40.2% HMI and 53.7% amplitude of H
      waves of the S1 H-reflex, 54.9% latency and 46.3% amplitude of H waves of the
      popliteal H-reflex, 40.2% SCV and 40.2% amplitude of sensory action potentials
      were diagnosed as abnormal. CONCLUSIONS: A high incidence rate of diabetic
      radiculopathy was confirmed to be comparable to that of proximal neuropathy and
      distal symmetrical sensory polyneuropathy. This suggests that diabetic neuropathy
      may be related to metabolic and/or vascular disorders.

PMID- 10923458
TI  - [Investigation of retroviral infection in human acute myeloid leukemia].
AB  - OBJECTIVE: To explore the potentiality of retroviral etiology in human acute
      myeloid leukemia (AML). METHODS: Cell culture techniques, direct immunogold
      silver staining(D-IGSS), reverse transcriptase (RT)assay, XC syncytium assay, and
      electron microscopy were employed to evaluate retrovirus associated antigens
      (RVAAgs), RT activities, CPE, and virus particles of both leukemic cells and
      normal hematopoietic cells. RESULTS: RVAAgs were detected by D-IGSS in 50.0% of
      fresh AML cell samples and 87.5% of cultured AML samples. RT assay showed that
      RVAAg-positive samples from 14 cases simultaneously expressed RT activities, and
      XC syncytium assay also revealed positive results. Electron microscopy
      demonstrated typical type C retrovirus particles at various maturation in 75% of
      cultured leukemic cell samples. In contrast, neither RVAAgs and RT activity nor
      syncytium and virus particles were detected in normal controls. CONCLUSIONS: AML
      cells harbor the entire genome(s) of retrovirus(es), which could release into
      extracellular spaces in intact particles via budding from the target cells
      stimulated in vitro by appropriate RV inducing agents. The exact relationship
      between these viruses and AML etiology is uncertain and needs further study.

PMID- 10923459
TI  - [Apoptosis of leukemic lymphocytes mediated by purinergic P2z receptors].
AB  - OBJECTIVE: To investigate the role of purinergic P2z receptors for apoptosis of
      human leukemic lymphocytes induced by extracellular adenosine triphosphate (ATP).
      METHODS: A total of 11 B-CLL patients were studied with regard to exposure of
      leukemic lymphocytes with (n = 8) or without (n = 3) P2z receptors to ATP,
      benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP), adenosine-5'-[gamma-thio]
      triphosphate (ATP-gamma S), and other nucleosides for 8 h in vitro. Apoptosis was
      detected by electron microscopy (EM), agarose gel electrophoresis, and
      quantitative assay-TdT assay. RESULTS: Apoptosis was detected only in leukemic
      lymphocytes with P2z receptors. Using a quantitative assay, we found that ATP
      induced DNA strand breaks occur specifically with BzATP, ATP and 2MeSATP, but not
      for analogue ATP-gamma S nor other nucleosides. Meanwhile, ATP-induced DNA
      fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a
      compound recently shown to block P2z receptors. Also, the Ca2+/calmodulin complex
      played a role in the regulation of the apoptosis induced by ATP on CLL cells,
      because an antagonist of this complex, 1-[N,O-bis (5-isoquinolinesulfonyl)-N
      methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) was found to inhibit the ATP-induced
      apoptosis. CONCLUSION: These data indicate that P2z receptors on lymphocytes play
      an important role in apoptosis induced by ATP in vitro.

PMID- 10923460
TI  - [Ultrastructural study on neuromuscular junction of patients with lambert-Eaton
      myasthenia syndrome or mitochondrial encephalomyopathy].
AB  - OBJECTIVE: To study the ultrastructural changes of neuromuscular junction (NMJ)
      in patients with lambert-Eaton myasthenia syndrome (LEMS) and mitochondrial
      encephalomyopathy (MEMS). METHODS: The MMJ of internal intercostal muscles from
      patients with LEMS, MEMS or cardiac disease (control group) was labelled by HRP
      BuTx and was quantitatively studied using image analysis system on electron
      microscopic photo. RESULTS: The ratio of nerve terminal area with postsynaptic
      membrane of NMJ was less in the MEMS group than controls. Both the length of
      presynaptic membrane and the ratio of the length of postsynaptic memberane to
      presynaptic membrane was larger in the LEMS group than in the MEMS group and
      controls, but the ratio of nerve terminal area with postsynaptic memberane area
      was less in the LEMS patients than in the MEMS group and controls. CONCLUSION:
      The areas of nerve terminal in the MEMS patients shrink because of mitochondrial
      damage. In LEMS patients however, the major change is the elongation of
      postsynaptic memberane and increasing of Ach receptors.

PMID- 10923461
TI  - [Telomerase activity in infiltration ductal carcinoma of breast].
AB  - OBJECTIVES: To compare telomerase activity of infiltration ductal carcinoma of
      breast with that of benign breast changes and to analyze the significance of
      telomerase activity in diagnosis of malignancy. METHOD: Telomerase activity was
      detected in 61 cases of infiltration ductal carcinomas of breast and 14 cases of
      benign changed breast using TRAP assay. RESULTS: Telomerase activity was detected
      in 49 of 61 (80.3%) cases of infiltration ductal carcinoma. Telomerase activity
      in infiltration ductal carcinoma was not related tumor grades, tumor size, lymph
      node metastasis status, even tumor tissue estogen receptor(ER) and progesterone
      receptor(PR) status. Telomerase activity was not present in 5 cases of breast
      fibrocystic disease. Weak telomerase activity was detected in 4 of 9 cases of
      breast fibroadenoma. These suggested that telomerase activity acquires in very
      early stage of breast cancer. CONCLUSION: Telomerase activity is only detected in
      most of infiltration ductal carcinomas of breast and few cases of fibroadenoma.
      Telomerase activity may play an important role in the development of breast
      cancer.

PMID- 10923462
TI  - [Costimulatory B7 molecules in drug induced interstitial nephritis and IgA
      nephropathy with tubulointerstitial injury].
AB  - OBJECTIVE: To evaluate the role of costimulatory B7 molecules in the pathogenesis
      of drug induced interstitial nephritis(D-TIN) and IgA nephropathy with severe
      tubulointerstitial injury(IgAN). METHODS: Renal biopsy materials from D-TIN(n =
      15) and IgAN(n = 15) were used. Cadaveric donors for kidney transplantation(n =
      10) served as normal controls. The lymphocyte subsets and the expression of B7-1,
      B7-2 and HLA-DR in the renal tissue were analyzed by immunohistochemistry
      staining. RESULTS: CD4+ and CD8+ cells in the interstitium markedly increased in
      patients with D-TIN. Parallelly, B7-1 and B7-2 expressing cells in the
      interstitium also augmented in this group of patients. The expression of B7-1 and
      HLA-DR on the renal tubular cells increased in patients with D-TIN. Although CD4+
      and CD8+ cells increased in the interstitium of IgAN, the B7-1 and B7-2
      expressing cells in the interstitium were not different from those of the normal
      controls. Although the renal tubular expression of B7-1 was upregulated in IgAN,
      the expression of HLA-DR kept in the normal range. CONCLUSION: These results
      indicate that the costimulatory molecules mediated T cell activation plays an
      important role in the pathogenesis of D-TIN. The interstitial infiltrating and
      tubular cells both act as an antigen presenting cells in the initiation of immune
      injury in D-TIN. However, such evidence has not been found in patients with IgAN.

PMID- 10923464
TI  - [Mechanism of coronary vasodilation in myocardial regional hypoxia].
AB  - OBJECTIVE: To determine if coronary vasodilation is dependent upon adrenergic
      activation during myocardial regional. METHODS: Studies were conducted in 10
      Mongrel dogs of either sexes, in which LAD was perfused with normoxic (CAO2 =
      18.4-20.4 ml/100 ml) or regional hypoxic (CAO2 = 7.8-8.1 ml/100 ml) blood with
      coronary perfusion system by self-control methods. RESULTS: No significant
      differences were observed in hemodynamic values with regional hypoxia compared
      with normoxia before adrenergic receptor blocker was given, but coronary blood
      flow increased by 225%. There were significant differences in dp/dt max, dp/dt
      min after adrenergic blocker was given. Whether there was regional hypoxia or
      not, coronary blood flow still increased by 190%. CONCLUSION: Coronary
      vasodilation is independent upon adrenergic activation during myocardial regional
      hypoxia.

PMID- 10923463
TI  - [Evaluation of the intubating conditions and maintenance doses of rocuronium].
AB  - OBJECTIVE: To assess intubating conditions after administration of rocuronium 0.6
      mg/kg at 60 or 90 s and neuromuscular blocking effects of rocuronium. METHODS:
      Thirty-two patients were randomly designated to two groups: 60 s group and 90 s
      group. Anesthesia consisted of thiopentone, fentanyl, N2O/O2 and enflurane. After
      a 2 x ED95 dose the trachea was intubated at 60 or 90 s and the intubating
      conditions were recorded. After intubation was finished, patients were allocated
      randomly to receive either intravenous infusion or bolus injection of rocuronium
      to maintain surgical relaxation. RESULTS: Intubating conditions were not
      different between the two groups and were found to be clinically acceptable (good
      or excellent) in all patients. The maintenance of surgical relaxation was
      satisfactory either with repeated bolus and infusion of rocuronium. CONCLUSION:
      Intubation can be performed under good to excellent conditions within 60-90
      seconds after a bolus dose of 0.6 mg/kg rocuronium. This indicates that
      rocuronium may be a suitable alternative to succinycholine during rapid-sequence
      induction of anesthesia.

PMID- 10923465
TI  - [The effect of expressed human apolipoprotein AI on plasma high density
      lipoprotein level in transgenic mice].
AB  - OBJECTIVE: To study the regulation of human apolipoprotein AI(h-apo AI) gene
      expression and its role in high density lipoprotein (HDL) metabolism. METHODS:
      Transgenic C57BL/6 mice established in this laboratory with human apoAI gene
      containing mouse metallothionein-I(MT-I) promoter were used for investigation.
      RESULTS: Southern blot identified the presence of 4-15 copies of h-apo AI gene in
      the transgenic mice. Northern blot showed that human apo AI mRNA was expressed
      mainly in the liver and kidneys, and the high level of h-apo AI mRNA was obtained
      in liver, kidneys and small intestine after Zinc(Zn) induction. Total Plasma
      apoAI Level in transgenic mice was significantly increased than that in the
      controls, and a high h-apoAI level was detected in the transgenic mice (46%
      increased after Zn induction). Additionally, total and HDL cholesterol levels
      were noticed to be highly increased to 47% before and 103% after Zn induction in
      the transgenic mice comparing to that of the controls. The plasma HDL and h-apoAI
      levels were significantly correlated (r = 0.85, P < 0.01) in the transgenic mice.
      CONCLUSION: Apo AI has a profound effect on regulating HDL levels in the
      transgenic mice. This animal model is considered appropriate for studying the
      effect of apoAI on lipid metabolism and the mechanism combating atherogenesis.

PMID- 10923466
TI  - [Gene expression in vivo mediated by adenoviral vector after direct gene transfer
      into anastomotic rat carotid arteries].
AB  - OBJECTIVE: To observe the efficiency and time course of gene expression in vivo
      mediated by adenoviral vector after direct gene transfer into anastomotic rat
      carotid arteries. METHODS: After being soaked in high concentration of glucose
      solution containing Adv5-CMV (control group) or Adv5-CMV/LacZ (treatment group)
      for 30 minutes, soluble stents were inserted into the lumina of cut rat carotid
      arteries and end-to-end anastomoses were performed. On the 2nd, 7th, 14th, 28th,
      60th and 90th day after surgery, the anastomotic carotid arteries of the two
      groups were explanted. All samples were analyzed for the presence of beta
      galactosidase activity and histochemical staining. RESULTS: beta-galactosidase
      activity was not detected in the carotid arteries of the control group.
      Microscopic examination of sections from vessels of the control group revealed no
      X-gal staining. The treatment group revealed bluestaining in all anastomotic
      arteries and in all layers of the arterial wall explanted including the intima,
      media, and adventitia on the 7th, 14th day postoperatively. CONCLUSIONS:
      Adenoviral vector could make foreign effectively transfer into rat carotid
      arteries in vivo. Mediated by adenoviral vector after direct gene transfer into
      anastomotic rat carotid arteries, the high level of gene expression only
      persisted about one month.

PMID- 10923467
TI  - [Radioimmunoimaging of hepatocellular carcinoma with 131I labeled antihepatoma
      monoclonal antibody Fab fragment].
AB  - OBJECTIVE: To study the effects of radioimmunoimaging (R11) of hepatocellular
      carcinoma with 131I labeled antihepatoma monoclonal antibody (HAb18) Fab
      fragment. METHODS: HAb18Fab was prepared by papain digesting HAb18, and it was
      radioiodinated with iodine-131 using high efficiency iodination method. The
      experiment consisted of two parts: ten nud mice bearing human hepatocellular
      carcinoma xenograft were injected intravenously with 131I-HAb18Fab 3,700
      kBq/mouse, and six patients with hepatocellular carcinoma were injected
      intravenously with 131I-HAb18Fab 111-166.5 mBq/body. RESULTS: Ten nud mice
      bearing hepatocellular carcinoma, showed positive image. The optimum imaging time
      was 4.5-12 h after injection, and was 21.07 +/- 0.05 for tumor/liver higher than
      5.83 +/- 0.05 of intact HAb18, and the reported 3.03. No tumor image was found in
      the control group of mice. Six patients with hepatocellular carcinoma, after
      injecting 131I-HAb18Fab 16 h, showed positive image. The optimum imaging time was
      16-24 h earlier than 96 h of the reported 131I. CONCLUSION: R11 with 131I
      HAb18Fab possesses the advantages of the location, qualitative analysis and
      earlier diagnosis. It is prospective in clinical application.

PMID- 10923468
TI  - [Effects of selective induceble nitric oxide synthase inhibitor on immunological
      hepatic injury in rat].
AB  - OBJECTIVE: To investigate the role and induced regulation of nitric oxide (NO) in
      rat immunological hepatic injury, and the effect of selective inhibitor on
      induceble nitric oxide synthase (iNOS). METHODS: The intracellular NOS gene
      expression in the immune damaged hepatocytes was determined by in situ PCR
      technique, and NO concentration and lactate dehydrogenase (LDH) activity in
      culture supernatant were measured. RESULTS: Administration of bacille calmette
      guerin (BCG, 15, 30, 50 mg/rat, i.v.) alone or BCG with the inflammatory
      cytokines mixture (CM), including IL-1 beta, IFN-gamma, TNF-alpha and
      lipopolysacchride (LPS) significantly increased NO production and LDH release in
      culture medium(P < 0.05). NO production was enhanced with hepatic injury degree
      in direct proportion, and with BCG dose in inverse proportion. Under
      immunological stimuli condition, hepatocytes NOS mRNA mainly expressed an
      induceble and soluble isoform (iNOS) in cytoplasm. Aminoguanidine (AG), a
      selective iNOS inhibitor, inhibited NO production and LDH release (83.4% and
      36.0%, P < 0.05), but the transcription inhibitor actinomycin D enhanced LDH
      level in the medium (25.5%, P < 0.05). CONCLUSION: NO produced by immunological
      stimuli participates in rat hepatic injury mechanism.

PMID- 10923469
TI  - [Correlation of interleukin 1 beta-converting enzyme(ICE) gene expression with
      gut epithelial cell apoptosis in septic mice].
AB  - OBJECTIVE: To investigate the correlation of gut epithelial cell apoptosis with
      ICE, IL1 beta gene expression in septic mice. METHODS: Sepsis was induced in mice
      by cecal ligation and puncture(CLP). Sham-operation group underwent the same
      manipulation but without CLP. 1, 3, 6 hours after CLP, gut epithelial cells, were
      isolated. IL1 beta, ICE gene expression was detected quantitatively by RT-PCR.
      Epithelial cell apoptosis was assessed by flow cytometric method and
      biochemically by DNA electrophoresis. RESULTS: The survival rate of CLP mice was
      1/10 as compared to 10/10 of sham-operation mice. IL1 beta, ICE mRNA expression
      in CLP mice was significantly higher than that in the sham-operation group(P <
      0.01); IL1 beta mRNA expression was parallel to ICE mRNA expression. The number
      of epithelial cell apoptosis was correlated excellently to the level of ICE, IL1
      beta mRNA expression. Epithelial cell apoptosis could not be detected in sham
      operation group at the indicated time points. CONCLUSION: ICE, IL1 beta gene
      overexpression may be involved in the vulnerability of epithelial cell apoptosis
      in septic mice.

PMID- 10923470
TI  - [Effects of glutamate, glutamate receptor in limbic system and hypothalamus on
      hypothalamus-pituitary-adrenal axis after rats MCAO].
AB  - OBJECTIVE: To investigate the features of activity changes of glutamate(Glu),
      glutamate receptors(GluR) in hippocampus and hypothalamus during rats middle
      cerebral artery occlusion (MCAO) or reperfusion. METHODS: Using radio-legend
      binding assay of receptor (RBA), high-performance liquid chromatography (HPLC)
      and hybridization in situ and radioimmunometric assay, (RIA), we determined the
      dynamic changes of Glu content, GluR capacity and it's Kd in cell membrane from
      the hippocampus of the ischemic brain and the hypothalamus CRHmRNA expression
      levels in every brain areas and ACTH concentrations in plasma at different time
      after middle cerebral artery occlusion(MCAO) or reperfusion. RESULTS: Glu content
      rapidly increased in the hippocampus and the hypothalamus at 15 minutes after
      MCAO, and reached the peak values at I1 h, and rapidly decreased to the basic
      line level after reperfusion. Glu content IR24 h to IR48 h, was elevated again
      moderately, and declined slowly 48 hours after reperfusion. The GluR was down
      regulated and the affinity enhanced in during the ischemic period. During the
      reperfusion period, the GluR was typically up-regulated. The CRHmRNA expressive
      levels were markedly enhanced in the tempol cortex, the hippocampus and the
      hypothalamus at I1 h, and kept to IR96 h, the ACTH concentration in the plasma
      increased relatively. In the peak time of reperfusion, the Glu content of
      hypothalamus was positively corrected with CRHmRNA expressive positive cell
      amounts of the hypothalamus. CONCLUSION: CRH may aggravate ischemic neuronal
      damage, and Glu participates in the pathogenesis of HPA axis be excited strongly
      and may be an important impel factor for ACI specially condition.

PMID- 10923471
TI  - [Molecular cloning and DNA sequencing of OspC gene of two strains Borrelia
      burgdorferi isolated in China].
AB  - OBJECTIVE: To investigate the variation of OspC gene in two Chinese isolates of
      Borrelia burgdorferi. METHODS: PCR technique was used to amplify the OspC gene
      from the whole cellular DNA of isolates BT01 and BJ-9011. The amplified products
      were inserted into plasmid pGEM-3ZF(+) and sequenced. RESULTS: Except the signal
      peptide, the OspC genes of the two isolates BT01 and BJ-9011 were 579 bp and 576
      bp which encode 193, 192 amino acids respectively. The nucleotide and amino acids
      sequence identity between the two strains was 86% and 83%. High homology exists
      between these Chinese isolates and several foreign isolates (PBi, PKo, B31),
      especially in BJ-9011. It had 99% nucleotide and amino acid sequence identified
      with B31. CONCLUSION: Variations in OspC genes are noted between the two Chinese
      Borrelia burgdorferi isolates and foreign isolates.

PMID- 10923472
TI  - [Nervous system complication after cardiac surgery].

PMID- 10923473
TI  - [Some aspects of immunity of vaccine in China].

PMID- 10923474
TI  - [Prevention of infectious disease in children with vaccination].

PMID- 10923475
TI  - [Conference on the clinical uses of human used vaccine in China].

PMID- 10923476
TI  - [Pediatric Haemophilus influenzae type b meninngitis in Hefei city: an
      epidemiologic study].
AB  - OBJECTIVE: To obtain epidemiologic information about Hib meningitis from Hefei.
      METHODS: Data were collected from 1990 to 1992 by a coordinative group including
      13 hospitals. All children with a clinical diagnosis of acute bacterial
      meningitis were enrolled and specimens were taken for etiologic studies. CSF and
      blood were tested by standard bacteriologic technique. CSF, blood and
      concentrated urine were tested directly for detecting antigen by CIE. The data
      were analysed by epidemiologic methods. RESULTS: Of 60 cases of bacterial
      meningitis clinically diagnosed, 31 (51.7%) were CIE positive for Hib antigen.
      Only 3 cases of CSF culture were positive for Hib. The annual incidence of Hib
      meningitis in Hefei was culculated as 4.81/100,000 children younger than 15 years
      and 10.66/100,000 children younger than 5 years. The case fatality rate was 9.7%.
      21.4% of survivors suffered from neurological or psychological problems.
      CONCLUSIONS: Using antigen detection combined with bacterial culture, we could
      make etiologic diagnosis in 90% of the cases. Hib is the most common cause of
      bacterial meningitis, but the incidence is much lower than in most parts of the
      world.

PMID- 10923477
TI  - [Immunogenicity and efficacy trials of live attenuated hepatitis A vaccines].
AB  - OBJECTIVE: To study two live vaccines, H2 and LA-1 strains, both attenuated in
      growth on human diploid cell culture at lower temperature (32 degrees C).
      METHODS: Randomized, controlled trials were performed among half million
      children. 135,340 children were divided into vaccine or control groups by
      individual and 360,012 by cluster. Those susceptibles with negative anti-HAV were
      bled at 2-6 months after the vaccination and blood test for anti-HAV. RESULTS: 37
      hepatitis A cases were found in the control group. The protective efficacy of the
      two vaccines was 100%, and the 95% lower confidence limit (one sided) of combined
      efficacy of the two vaccines was 92.1%, that was comparable with the two
      inactivated vaccines produced by SmithKline beecham or Merck Sharp Dhome.
      CONCLUSION: The vaccines are safe, and the seroconversion to H2 strain (10(7.0)
      TCID50) and LA-1 strain (10(6.75) TCID50) is 94.87% and 83.16% respectively.

PMID- 10923478
TI  - [Cloning and expression of subunit genes of pertussis toxin and its immunological
      evaluation].
AB  - OBJECTIVE: To clone the gene encoding pertussis toxin (PT) from Bordetella
      Pertussis CS strain and five genes encoding subunits of PT, to investigate the
      possibility of expressing the genes encoding for mature methionyl subunits of PT
      in insect cell and to evaluate the immunological characteristics of recombinant
      subunits. METHODS: The genes encoding for PT and its subunits were cloned by PCR
      and confirmed by restriction enzyme digestion and Southern blot. Using
      recombinant baculovirus technology, the recombinant subunits were expressed in
      Sf9 insect cells and analyzed by immunofluorescence assay. The immunological
      properties of recombinant subunits were analyzed by ELISA. RESULTS: The genes
      encoding for PT and its subunits were cloned and expressed in Sf9 cells. The
      level of specific antibodies against nature PT induced by five recombinant
      subunits polymerized was higher than that unpolymerized and polymerized by four
      recombinant subunits (without S1) in mice. The results indicate that PT subunits
      had weak ability to induce specific antibodies against PT, and also anti-nature
      PT sera had poor recognition to PT subunits. CONCLUSION: The ability of PT to
      induce specific antibody is conformation dependent of intact PT, and antibody
      induction domains are located dominantly in S1 subunit of intact PT.

PMID- 10923479
TI  - [Production of purified Japanese encephalitis vaccine from Vero cells with roller
      bottles].
AB  - OBJECTIVE: To study the production process of purified Japanese encephalitis (JE)
      vaccine from Vero cells cultivated in roller bottles to improve the quality of JE
      vaccine. METHODS: The 15 L roller bottles were used for propagation of Vero cells
      and JE virus, then the virus was inactivated, concentrated, treated by protamine
      sulphate, purified by sucrose gradient density centrifugation and lyophylized as
      final product. RESULTS: Three batches of high quality lyophylized vaccine were
      produced and the quality control tests of vaccine for human use had been passed.
      CONCLUSION: Using roller bottles to cultivate continuous cell line-Vero cells for
      JE vaccine production is feasible.

PMID- 10923480
TI  - [Research on human vaccine and its trends of application].

PMID- 10923481
TI  - [Compartmental distribution of hepatitis C virus quasispecies in mononuclear
      cells and liver].
AB  - OBJECTIVE: To explore the role of the infection of monouclear cells by hepatitis
      C virus(HCV) in the chronicity of HCV infection. METHODS: Direct sequencing of
      the amplified hypervariable region (HVR) gene of HCV was used to distinguish main
      HCV quasispecies infecting non-hepatocytes from those infecting hepatocytes and
      circulating virions. The main HCV quasispecies in peripheral blood mononuclear
      cells(PBMC), liver-associated mononuclear cells (LAMC), serum and liver samples
      from 6 patients with chronic hepatitis C and from 6 patients with HCV-related
      cirrhosis were analysed and compared. RESULTS: The main HCV qusispecies in the
      livers were different from those in PBMC in 3 transplanted cirrhotic patients and
      5 patients with chronic hepatitis C. Different substitutions existed between PBMC
      and LAMC in 3 of 6 patients analysed. Mutations were observed within the first 50
      amino acids of E2 gene, which induced amino acid change in 6 of 9 patients
      analysed. CONCLUSION: In chronically infected patients, the detection of HCV RNA
      in mononuclear cells is not due to the adsorption of circulating virions but a
      significant infection. The compartmental distribution of HCV quasispecies in
      hepatocytes and mononuclear cells could be involved in the chronicity of HCV
      infection.

PMID- 10923482
TI  - [Alteration of fatty acid components of erythrocyte membrane and insulin
      resistance in diabetic patients].
AB  - OBJECTIVE: To study the effect of alteration of erythrocyte membrane fatty acid
      components and fluidity on insulin resistance (ISR) in NIDDM patients. METHODS:
      The fatty acid(FA) components and fluidity of erythrocyte membrane in 52 NIDDM
      patients with and without hyper-insulinemia were examined by a high-performance
      liquid chromatographic method and flourescence polarization technique. RESULTS:
      The content and composition erythrocyte membrane arachidonate (AA) were
      significantly lower in NIDDM patients than in controls, and also markedly lower
      in patients with hyperinsulinemia than those without hyperinsulinemia. The
      diabetics had increased erythrocyte membrane microviscosities as compared with
      controls, and membrane microviscosities were higher in diabetics with
      hyperinsulinemia than those without hyperinsulinemia. AA contents of erythrocyte
      membrane were negatively correlated with membrane membrane microviscosities and
      positively with ISI in NIDDM patients. CONCLUSION: In NIDDM patients,
      hyperinsulinemia and ISI bring about AA metabolic abnormalities and decreased AA
      contents in cell membrane. Alteration of cell membrane FA components results in
      the changes of membrane fluidity, and the latter can increase IRS.

PMID- 10923483
TI  - [Engineered glutamic acid decarboxylase fusion protein in diagnosis of type I
      diabetes mellitus].
AB  - OBJECTIVE: To get recombinant GAD 65 proteins which have immunogenicity by the
      method of gene engineering so that the recombinant protein can be used for early
      diagnosis in type I diabetes mellitus. METHOD: We amplified the complete fragment
      encoding GAD65 gene by PCR, and expressed its protein in E. coli. DH5 alpha after
      inserting it in the vector and determining its nucleotide sequence.
      Consequentially, we attempted to prove the immunogenicity of expresion products
      and construct a method for detecting antibodies against GAD65 in Diabetic serum.
      RESULT: The sequence analysis showed that the amplified fragments contained 1758
      bp, encoded 585 amino acid, and had been correctly inserted into pGEX-3X vector.
      The recombinant proteins expressed in E. Coli. DH5 alpha had immunogenicity and
      could be used to detect agtibodies against GAD65 in diabetic serum. CONCLUSION:
      We have got recombinant GAD65 proteins which have immunogenicity and have used
      them to detect preliminarily antibodies against GAD65 in diabetic serum.

PMID- 10923484
TI  - [Nucleoside diphosphate kinase/nm23H1 expression in ovarian epithelial carcinoma:
      retroperitoneal lymphatic metastasis and survival].
AB  - OBJECTIVE: To determine the relationship between NDPK(A) expression and
      retroperitoneal lymph node metastasis (LNM) and the significance of the prognosis
      in epithelial ovarian carcinoma. METHODS: NDPK(A) expression of formalin-fixed
      parafin-beded samples, which included 74 primary, 31 intraperitoneal and 18
      retroperitoneal lymph node metastatic tumors, were examined by ABC
      immunohistochemisty in 74 patients with primary ovarian cancer. RESULTS: In the
      74 primary lesions, 22 samples showed positive staining of NDPK(A) (30%).
      Positive staining was higher in patients without LNM(46%) than those with LNM
      (17%, P = 0.008); it was lower in menopausal patients (19%) than in menstruant
      (44%, P = 0.022). Compared with primary tumor, NDPK(A) expression appeared to
      decrease in lymph-node lesion(28% vs 39%, P > 0.1) but to increase in
      intraperitoneal metastastic tumor (32% vs. 19%, P > 0.5). Multivariance analysis
      confirmed that the important risk factors for LNM were lower expression of
      NDPK(A), more large residual tumor and poor differentiation. But there was no any
      corelation between NDPK(A) expression and survia. CONCLUSION: The study suggested
      that increased expression of NDPK(A)/nm23H1 is inversely related to LNM in
      epithelial ovarian carcinoma, but it can not confirm the prognostic significance
      of NDPK(A).

PMID- 10923485
TI  - [The effect of HCV NS3 protein on expression of p53 gene protein in
      hepatocarcinogenesis].
AB  - OBJECTIVE: To investigate hepatocarcinogenesis by detecting the effect of HCV NS3
      protein on expression of P53 protein in hepatocellular carcinoma (HCC) and
      pericarcinomatous liver tissue. METHODS: The expression of HCV NS3 and P53
      protein was detected by immuno-histochemical technique (SP method) in specimens
      of HCC and their surrounding liver tissues from 47 patients with negative HBV.
      RESULTS: The positive rate of HCV NS3 protein was lower in HCC(62%) than in
      pericarcinomatous liver tissue(83%) (P < 0.025). The expressive strength of HCV
      NS3 protein in HCC was related to the degree of carcinomatous cell
      differentiation(P < 0.025). The positive rate of P53 protein in carcinomatous
      tissue(81%) was higher than in pericarcinomatous liver tissue (47%)(P < 0.025).
      The worse differentiation of cancer cells, the stronger expression of P53 protein
      (P < 0.05). The expression of P53 protein was not correlated with the expression
      of HCV NS3 protein in carcinomatous tissiue (P > 0.5), whereas their expression
      was closely related in pericarcinomatous liver tissue(P < 0.01), and the
      expressive rate of P53 protein in the cases of positive HCV NS3 protein was
      higher than that in the cases of negative HCV NS3 protein. CONCLUSION: HCV NS3
      protein may exert its hepatocarcinogenic effect in early stage on host cells by
      endogenous pathway which may bring about mutation of p53 gene and transformation
      of hepatocytes.

PMID- 10923486
TI  - [Cellular biological mechanism of leukocytosis produced by all-trans retinoic
      acid: a preliminary study].
AB  - OBJECTIVE: To investigate the cellular biological mechanism of leukocytosis
      produced by all-trans retinoic acid (ATRA). METHODS: BALB/C mice were fed by
      ATRA. The effects of ATRA on BALB/C mice hematopoiesis was studied by 3H-TdR,
      semi-solid progenitor culture, and CFU-S number. RESULTS: ATRA increased the
      peripheral blood cells count in vivo. The effect on WBC count was obvious. The
      peak of the elevation (183% of the control) occurred at the 16th day.
      Correspondingly, 3H-TdR was increased and CFU-S was enhanced in BM, and the peak
      of the elevation (190% and 200% of the control, respectively) occurred at the 8th
      day. The progenitor cell CFU-GM was proliferated and the maximum elevation (215%
      of control) was observed at the 12th day. CONCLUSION: ATRA could produce
      leukocytosis in normal BALB/C mice. The effect was possibly related to the
      proliferation of CFU-GM and CFU-S and to ATRA-induced CSA such as G-CSF in vivo.

PMID- 10923487
TI  - [Proliferative effect of low energy laser and colony stimulating factor on human
      umbilical cord blood hematopoietic cells].
AB  - OBJECTIVE: To study the proliferative effect of low energy laser on human cord
      blood hematopoietic cells in vitro and the relationship between the effect of low
      energy laser and colony stimulating factor (CSF). METHODS: Human umbilical cord
      blood hematopoietic cells were irradiated with copper vapour laser and cultured
      in vitro. The number of colony and cells was calculated. RESULTS: Laser
      irradiation synergized with CSF in expansion of cord blood hematopoietic cell.
      The GM-CFUc number from the group treated with irradiation plus CSF increased
      significantly as compared with that from other groups including laser irradiation
      or CSF treatment alone or control (P < 0.01). Reincubation of cord blood cells in
      the soft agar medium revealed that secondary colonies were formed and the
      absolute number of colony was obviously increased as compared with that before
      liquid culture. The number of colony in irradiation group was more than these of
      non-irradiation group. CONCLUSION: Low energy laser irradiation for cord blood
      stem cells is effective in vitro expansion of cord blood stem cells.

PMID- 10923488
TI  - [Regulative effect of nuclear factor kappa B on the expression of intercellular
      adhesion molecular-1 in human mesangial cells].
AB  - OBJECTIVE: To study the regulative effect of nuclear factor kappa B (NF-kappa B)
      on the expression of intercellular adhesion molecular-1(ICAM-1) in human
      mesangial cells (HMC) by interleukin I-1 beta (IL-1 beta). METHODS: Activation of
      NF-kappa B was measured by electrophoresis mobility shift assay (EMSA). ICAM-1
      expression was detected by Northern Blot and Cell ELISA. RESULTS: rhIL-1 beta (10
      ng/ml) could rapidly stimulate activation and translocation of NF-kappa B, and
      also could enhance the expression of ICAM-1 in mRNA (0.14 vs 0.35) and protein
      (0.92 +/- 0.10 vs 1.35 +/- 0.11, P < 0.01) level. After pretreatment with 100
      mumol/L L-1-chlor-3-(4-tosylamido)-4-phenyl-2 butanon (TPCK), an inhibitor of NF
      kappa B, both ICAM-1 levels of mRNA and protein stimulated by rhIL-1 beta were
      blocked by about 50% in these cells (0.46 +/- 0.05 vs 1.29 +/- 0.12, P < 0.01)
      compared with the rhIL-1 beta-stimulated group. CONCLUSION: These results suggest
      that NF-kappa B is one of the signaling factors for IL-1-stimulated ICAM-1
      expression in HMC. It may modulate the immune-inflammatory process in glomerular
      diseases.

PMID- 10923489
TI  - [Antisense to cyclin D1 inhibits the proliferation of glomerular mesangial
      cells].
AB  - OBJECTIVES: To investigate the role of Cyclin D1 in the proliferation of
      glomerular mesangial cells. METHODS: We first detected the expression of Cyclin
      D1 protein in mesangial cells by using immunohistochemical method, set up a
      retroviral vector mediated genetransfer system expressing Cyclin D1 antisense RNA
      with recombinating techniques, and assay the proliferating situation of
      genetransferred mesangial cells by MTT method and flow cytometry respectively.
      RESULTS: Cyclin D1 protein was expressed in the nuclei of cultured mesangial
      cells in vitro. The exgoenous gene was transducted into mesangial cells mediated
      by retrovirus and transcripted and expressed antisense RNA in high effiency. The
      response of antisense Cyclin D1 genetransferred mesangial cells to Endothelin-1
      (OD570)(18 hr 0.105 +/- 0.009 vs 6 hr 0.096 +/- 0.013) was not significant (P >
      0.05), but normal cells (18 hr 0.259 +/- 0.080 vs 6 hr 0.100 +/- 0.007) and only
      vector transferred cells (18 hr 0.278 +/- 0.020 vs 6 hr 0.097 +/- 0.008) were
      significant (P < 0.01). The progression of cell cycle was prevented from G1 to S
      phase by antisense Cyclin D1, and the percentage of cells of S phase in antisense
      Cyclin D1 genetransferred cells (12.70 +/- 3.39) was significantly reduced (P <
      0.01) as compared with normal cells (29.98 +/- 3.26). CONCLUSIONS: Cyclin D1 is a
      key regulatory protein of G1 progressing of cell cycle of mesangial cells, and
      the cellular proliferation stimulated by Endothelin-1 can be suppressed
      prominently in antisense Cyclin D1 gene transducted mesangial cells.

PMID- 10923490
TI  - [The mucosa of pediculed duodenal wall graft transplanted to the stomach in
      Wistar rats: histological and electronmicroscopic observations].
AB  - OBJECTIVE: To study the development mechanism of gastric metaplasia in the
      duodenum through the transplantation of a flap of duodenal wall with vascular
      pedicle to the stomach. METHODS: The pedicled duodenal wall flaps of Wistar rats
      were transplanted to their stomaches. After the operation the rats were killed at
      the 3th, 6th, 9th and 12th month respectively, and histological change of the
      duodenal wall grafts was observed with optical and electron microscopy. RESULTS:
      Gastric metaplasia was found in the mucosa of duodenal wall grafts transplanted
      to the stomach at the 6th, 9th and 12th month. CONCLUSIONS: The formation of
      gastric metaplasia in the duodenal mucosa may be related to a change of the
      microenvironment around the tissues, and duodenal mucosa may differentiate into
      gastric epithelium by the decrease of pH value.

PMID- 10923491
TI  - [Antiandrogen treatment for nude mice model with ectopic transplanted human HCC].
AB  - OBJECTIVE: To investigate the effect of antiandrogen on hepatocellular carcinoma
      (HCC). METHODS: Nude mice model with orthotopic transplanted human HCC was
      constructed and the androgen receptor (AR) in tumor and surrounding liver tissue
      was assayed dynamically. Nude mice with ectopic transplanted HCC were treated
      with flutamide (blocker of AR) at two different dosages (Group F1, F2), normal
      saline(Group C), and anticancer drug(Group M). The effect of treatments was
      compared among the groups. RESULTS: The quantity of AR in nucleus and cytoplasm
      in tumor and tumor-surrounding tissue decreased with the increasing size of tumor
      in proper order. AR in tumor was significantly less in F1 and F2 groups than in
      other groups. The tumor weight of group F1, F2 and C had no significant
      difference (1.36 +/- 0.82 g, 2.66 +/- 1.40 g, 1.66 +/- 0.79 g, respectively), but
      was significantly higher than that of group M. CONCLUSION: Androgen may play a
      role at the initial stage of hepatocarcinogenesis, and antiandrogen therapy may
      be ineffective in the established tumor.

PMID- 10923492
TI  - [10-Hydroxycamptothecin induces apoptosis in human T24 urinary bladder cancer
      cells].
AB  - OBJECTIVE: To study the emechanisms of 10-Hydroxycamptothecine (HPT) inhibiting
      human urinary bladder cancer. METHODS: Using flow cytometry, electron microscopy
      and fluorescence microscopy, we studied the effects of HPT on human T24 urinary
      bladder cancer cells. RESULTS: HPT at 0.005 mg/L inhibited T24 bladder cancer
      cells by preventing the cells from S phase to G2/M phase and did not induce
      apoptosis. The apoptotic cells were induced by HPT at the concentration of 0.01
      0.10 mg/L. CONCLUSION: HPT can inhibit human T24 urinary bladder cancer cells and
      induced apoptosis at some concentrations. The induction of apoptosis is a very
      important mechanism of 10-Hydroxycamptothecine to treat urinary bladder cancer
      cells.

PMID- 10923493
TI  - [The studies on MTS1/p16 gene deletion during transformation of human bronchial
      epithelial cells].
AB  - OBJECTIVE: To detect the deletion of MTS1/p16 and the expression of P16 protein
      during the transformation of human bronchial epithelial cell line M. METHODS:
      Dual-color fluo-rescence in situ hybridization (FISH), immunohistochemical
      staining and western blot analysis were carried out. RESULTS: No deletion of
      MTS1/p16 gene was found in MP18 cells of the cell line M. But partial deletions
      occurred in the MP36 and MP120 cells of the cell line M. Immunohistochemical
      analysis and western blot test showed lower expression of P16 protein in the
      MP120 cells than in MP20 cells. CONCLUSIONS: MTS1/p16 gene deletion contributes
      to the malignant transformation of the human bronchial epithelial cell line M.
      Also FISH is a useful technique in detecting gene deletion.

PMID- 10923494
TI  - [Human bone morphogenetic protein-2: recombinant expression in E. coli].
AB  - OBJECTIVE: To explore the way of producing human bone morphogenetic protein
      2(hBMP-2) for bone healing by using the gene engeneering techniques. METHODS:
      hBMP-2 cDNA fragment, which consists of 3' end partial propeptide and mature
      peptide sequence, was inserted into the multiple cloning site of expression
      vector pkpL-3a via ligation. The recombinant plasmid pkpL-3a/hBMP-2 was
      transformed into E. coli pOp2136. By the method of restriction map, the positive
      expression clone was selected. SDS-PAGE analysis showed a new foreign protein
      band near 27,000 after induction. The yield of induced hBMP-2 accouned for 10% of
      the total bacterial proteins. RESULTS: The partial purified recombinant hBMP-2
      was implanted into Wistar rat thigh. After 4 weeks, histological analysis showed
      that it induced the proliferation of mesenchymal type cells and formation of new
      cartilage and bone in the implantation area. CONCLUSION: The hBMP-2 produced by
      gene engeneering techniques has the biologic capacity of ectopic bone formation.

PMID- 10923496
TI  - [Critical medicine facing challenge].

PMID- 10923495
TI  - [The relations between electrical synapse and the mechanism of epilepsy in
      genetical epilepsy-prone rat].
AB  - OBJECTIVE: To investigate the role of gap junction protein Cx32 formed electrical
      synapses in the pathogenesis of epilepsy. METHODS: Antisense
      oligodeoxynucleotides (ODN) techniques, intracerebroventricular injection,
      neuronal discharges in temporal cortex slices, in situ hybridization and
      immunohistochemistry were used. RESULTS: An antisense ODN for Cx32 100 micrograms
      was intracerebroventricularly injected once daily, for 3 days to P77PMC rat. The
      audiogenic seizure scores were significantly lowered as compared with the
      corresponding sense ODN (or PBS) treated control groups. Moreover, in the
      enterhinal cortex of the temporal cortex slice of antisense ODN treated P77PMC
      rat, the typical seizure like events and the late recurrent discharges were not
      induced by lower Mg2+ solution. The frequency and amplitude of neuronal
      discharges were decreased as compared with the control group. In situ
      hybridization and immunohistochemistry studies confirmed that Cx32 mRNA
      expression and Cx32 synthesis were also inhibited by Cx32 antisense ODN in P77PMC
      rat brain. CONCLUSION: Our results confirmed that gap junction formed electrical
      synapse between neurons plays an important role in the development of
      synchronization of neuronal discharges in vivo and in vitro.

PMID- 10923497
TI  - [Nutritional support in infectious diseases].

PMID- 10923498
TI  - [Prospects of study in multiple organ dysfunction syndrome].

PMID- 10923499
TI  - [The significance of point-inflection at static pressure-volume curve in optimal
      PEEP at early stage of ARDS in sheep].
AB  - OBJECTIVE: To study the optimal level of PEEP at early stage of ARDS. METHOD: The
      parameters of hemodynamics, lung mechanics, and gas exchange were compared at
      different levels of PEEP, including maximal static compliance PEEP, point
      inflection PEEP, 3 cmH2O higher or lower than point-inflection PEEP, and zero end
      expiratory pressure. RESULTS: Point-inflection PEEP (6.8 +/- 1.4 cmH2O) was
      significantly lower than maximal static compliance PEEP (9.3 +/- 1.4 cmH2O), P <
      0.01. The hemodynamic parameters were not significantly different in point
      inflection PEEP compared with 0cmH2O-PEEP (P > 0.05), but oxygenation index
      (PaO2/FiO2) and lung mechanics (static compliance and airway resistance) were
      improved significantly at point-inflection PEEP (P < 0.01). At maximal static
      compliance PEEP or 3 cmH2O higher than point-inflection PEEP, the hemodynamic
      parameters and PaO2/FiO2 were not different from those at point-inflection PEEP
      (P > 0.05). The pulmonary vascular resistance index (PVRI) was significantly
      higher (P < 0.05) and the mean airway pressure and peak inspiratory pressure
      increased significantly (P < 0.01). CONCLUSION: In the treatment of early ARDS,
      the PEEP needed may be lower than the "optimal PEEP" determined by obtaining the
      maximal static compliance. The application of point-inflection PEEP determined at
      inspiratory static pressure-volume curve was appropriate as the best PEEP.

PMID- 10923500
TI  - [Effect of recombinant human growth hormone on hypoalbuminemia in peritoneal
      sepsis: experimental and clinical research].
AB  - OBJECTIVE: To investigate the effect of recombinant human growth hormone(rhGH) on
      hypoalbuminemia in peritoneal sepsis. METHODS: We observed rhGH on albumin mRNA
      expression and albumin sythesis in vitro and in vivo with the method of reverse
      transcriptional polymerase chain reaction (RT-PCR). RESULTS: rhGH significantly
      up-regulated albumin mRNA expression in vitro (143 +/- 6 vs 100.4 +/- 2.2, P <
      0.01) and in vivo(152 +/- 8 Vs 100 +/- 3, P < 0.01), and obviously alleviated the
      inhibition of albumin mRNA expression induced by LPS (P < 0.05). In cecal
      ligation and puncture-induced septic rats, rhGH significantly raised albumin
      synthesis(20.4 +/- 1.7 Vs 15.5 +/- 2.9 g/L, P < 0.01) and albumin mRNA
      expression. In patients with peritoneal sepsis, rhGH in combination with total
      parenteral nutrition markedly increased serum albumin, prealbumin, and
      transferrin concentration, but no apparent effect was observed in controls.
      CONCLUSION: rhGH significantly increases albumin mRNA expression and albumin
      synthesis in peritoneal sepsis.

PMID- 10923501
TI  - [Analysis of critically ill patients with bacteremia].
AB  - OBJECTIVE: To study the epidemiology of bacteremia of critically ill patients and
      the mortality associated with bacteremia and risk factors for death in an
      intensive care unit. METHOD: 75 patients with 116 episodes of bacteremia were
      retrospectively studied. RESULTS: The mortality rate of the patients was 43%.
      Staphylococci (29%), Enterococci (12%), Class I inducible beta-lactamase
      producing Enterobacter (12%), extensive spectrum beta-lactamase-producing
      Enterobacter (10%) were the most common pathogens, among which gram-positive
      organisms constitute a major part. The most commonly affected organs were
      respiratory (77%), hepatic (53%), circulatory (53%), gastrointestinal (50%),
      renal (47%), central nervous (36%), and hemopoietic systems (27%). Multiple organ
      failure accounted for 76%. Univariate analysis revealed that the severity of
      underlying illness, multiple organ failure (MOF), septic shock, hepatic failure,
      renal failure and infection focus were the risk factors for in-hospital death (P
      < 0.05). Cox proportional hazard model analysis suggested central nervous system
      failure, septic shock, hemopoietic failure, hepatic failure and respiratory
      manipulation significantly affected the survival time of patients with bacteremia
      (P < 0.05). CONCLUSION: Gram-positive organisms are major pathogens of bacteremia
      in critically ill patients. Antibiotic therapy can not prevent the occurence of
      bacteremia, nor can it improve the prognosis.

PMID- 10923502
TI  - [Hypoxia impacts expression of nitric oxide synthase mRNA of different segments
      of intrapulmonary arteries].
AB  - OBJECTIVE: To investigate expression and localization of nitric oxide synthase
      (cNOS) mRNA of normoxic pulmonary arteries and the impact of hypoxia on its
      expression. METHODS: In situ hybridization was performed on each lung sections
      from rats in 1-week hypoxic group, 2-week hypoxic group, and control group to
      detect cNOS mRNA expression and localization by using cRNA probe for NOS.
      RESULTS: The positive score of cNOS mRNA expression by endothelial cells of
      pulmonary arteries associated with bronchioli was significantly higher than that
      of arteries associated with respiratory or terminal bronchioli (q = 8.13, 5.49, P
      < 0.01) in the control rats. In the 1-week hypoxic group or the 2-week hypoxic
      group, however, cNOS mRNA expression by endothelial cells of pulmonary arteries
      associated with either respiratory or terminal bronchioli was markedly decreased
      compared with that of the control group. No significant difference was found in
      cNOS mRNA expression by smooth muscle cells of each segments of pulmonary
      arteries (F = 2.26, P > 0.05). However, cNOS mRNA expression by smooth muscle
      cells of pulmonary arteries associated with respiratory bronchioli or terminal
      bronchioli was significantly decreased in the 1-week or the 2-week hypoxic group
      compared with the control group. CONCLUSION: These findings suggest that NOS mRNA
      expression by endothelial cells is greater in the larger, more proximal pulmonary
      arteries than at the periphery. Chronic hypoxia mainly impairs cNOS mRNA
      expression by proximal pulmonary artery endothelial cells and periphery pulmonary
      artery smooth muscle cells.

PMID- 10923504
TI  - [Effects of protein kinase C on non-heart organ protection of preconditioning].
AB  - OBJECTIVE: To investigate the effects of protein kinase C (PKC) on ischemic
      (hypoxic) preconditioning (PC) in the non-heart organs and tissue. METHODS: In
      the models of ischemia/reperfusion of in situ perfused rat small intestine, limb,
      and in the model of hypoxia/reoxygenation of cultured rat aortic vascular smooth
      muscle cells (VSMC), the effects of PKC on ischemic (hypoxic) PC were observed.
      RESULTS: PKC inhibitor H7 and polymyxin B completely abolished the protective
      effects of ischemic PC on small intestine and limb subjected to
      ischemia/reperfusion injury. Hypoxic PC activated PKC in VSMC and potentiated
      phosphorylation mediated by PKC. CONCLUSION: The activation of PKC is also the
      important chain of PC on non-heart organs, and its mechanism might involve
      protein phosphorylation.

PMID- 10923503
TI  - [The relationship between LPS-induced apoptosis in hepatocyte, Kupffer cell and
      hepatocytic damage].
AB  - OBJECTIVE: To study the role of tumor necrosis factor (TNF alpha) in the
      mechanisms of liver injury and the relationship between LPS-induced apoptosis in
      hepatocyte (HC), kupffer cell (KC), and hepatic damage. METHODS: In vitro,
      kupffer cells (1 x 10/ml) were stimulated with different concentrations of
      endotoxin (1-10 micrograms/ml) for 1-24 hr; the kupffer cells, which had been
      cultured with endotoxin for 24 hr, were isolated to coculture with hepatocytes
      (1:1) for 1-24 hr. Two kinds of cells of apoptosis and the block effect of TNF
      alpha antibody were detected by cell death ELISA, and the supernatant was
      performed to determine the levels of alanine aminotransferase (ALT), lactate
      dehydrogenase (LDH) at different time points. RESULTS: Following stimulation with
      LPS, the number of positive apoptotic KC increased in a concentration and time (3
      h-24 h) dependent manner. In contrast, coincubation of HC with LPS-stimulated KC
      resulted in a marked increase in positive apoptotic hepatocyte when LPS
      concentration was greater than 1 microgram/ml. TNF alpha antibody blocked
      apoptosis in both KC and HC. Only when the LPS concentration was higher than 1
      microgram/ml and cultured for 6 hr, the release of liver enzymes (ALT, LDH),
      responsible for hepacyte damage, rose significantly, but the process was behind
      of apoptosis, and TNF alpha antibody couldn't block it. CONCLUSION: TNF alpha
      mediates LPS-induced apoptosis in KC and HC, and the apoptosis precedes cellular
      damage. Massive apoptosis of KC may lead to the decrease of clearance of LPS,
      thereby exacerbating septic shock, hepatocyte damage and apoptosis.

PMID- 10923505
TI  - [Effects of different expression levels of fibronectin on biological behavior of
      tumor cells].
AB  - OBJECTIVE: To study the effects of fibronectin(FN) on tumor cell proliferation,
      adherence and invasion. METHODS: FN cDNA was introduced into a transitional
      carcinoma cell line 253J which expressed low level of FN, and 253 FN line which
      expressed higher level of FN was established. The changes of cellular
      proliferation in vitro were observed. Adhesiveness to the extracellular matrix
      was detected by MTT method. Hemotypic adhesion was investigated by detachment
      assay and invasiveness of the cells was observed with Boyden Chamber before and
      after FN cDNA gene transfection. RESULTS: The growth rate of 253-FN was decreased
      as compared with its parental cell 253J. Hemotypic adhesion was significantly
      increased. The adhesiveness of the cells to extracellular matrix was enhanced.
      Invasion assay showed that invasioness of 253-FN was decreased. CONCLUSION: This
      study suggested a correlation between FN expression and its biological behavior.
      With increased FN level, malignant phenotype was changed and invasive ability was
      inhibited.

PMID- 10923506
TI  - [Embryonic motoneurons transplanted into denervated skeletal muscles].
AB  - OBJECTIVE: To observe the living situation of homografting embryonic motoneurons
      in denervated skeletal muscles. METHODS: We transplanted dissociated ventral
      spinal cord cells from 12 embryonic days rats prelabeled with 5-bromo-2
      deoxyuridine(Brdur) into denervated skeletal muscles of adult rats. The
      denervated skeletal muscles were collected at 9 and 22 weeks respectively, and
      Nissl, acetylcholinesterases immunocytochemistry and ATPase staining were used to
      show the transplanted embryonic motoneurons and the morphography of muscle
      fibers. RESULTS: Transplanted embryonic motoneurons could survive, extend out
      long axons, and form neuromuscular junctions with muscle fibers. Type grouping
      fibers with bigger transverse area were also observed in the experimental group.
      Muscle fibers were much smaller and did not form fiber type grouping in the
      control group. CONCLUSION: Homografting embryonic motoneurons could survive well
      and reinnervate the denervated skeletal muscles.

PMID- 10923507
TI  - [Inhibition of human stomach cancer metastasis in vivo by anti-P-selectin
      monoclonal antibody].
AB  - OBJECTIVE: To study the role of cell adhesion molecule P-selectin monoclonal
      antibody (Mab) in tumor metastasis of an orthotopic implantation metastatic
      model. METHODS: SCID mice were implanted orthotopically using SGC-7901 human
      stomach carcinoma intact tissue. Three days later, animals were given i.v.
      injections of PBS or P-selectin Mab (100 micrograms/injection) twice weekly for 3
      weeks. 42 days after operation, all animals were sacrificed. Tissues from stomach
      and other organs were obtained for histopathological evaluation. RESULTS: Ten of
      the animals (n = 11) treated with PBS developed metastatic tumors in the regional
      lymph nodes, liver, and lung. In contrast, 2 of the animals (n = 9) treated with
      P-selectin Mab developed metastatic tumors in the organs examined. The level of P
      selectin mRNA expression determined by RT-PCR in gastric carcinoma tissue of SCID
      mice with tumor metastas is was higher than that without metastasis. CONCLUSIONS:
      The expression of P-selectin adhesion moleculeis associated with tumor
      metastasis, and the metastasis can be arrested by the Mab.

PMID- 10923508
TI  - [Three-dimensional reconstruction of electron beam computed tomography
      angiography for evaluating coronary artery bypass graft patency].
AB  - OBJECTIVE: To probe into the value of electron beam computed tomography (EBCT)
      for evaluating coronary artery bypass graft (CABG) patency follow-up. METHODS:
      EBCT enhanced single slice mode (SSM) and flow study were performed in 150
      patients. The results of 3-D reconstruction of CABG were correlated with bypass
      operation records and coronary arteriograms in 7 patients. RESULTS: 318 of 399
      coronary bypass grafts including IMA in 87/100(87%) and SVG in 228/296(77%) were
      patent. The overall patent rate was 79.7%. In 7 patients with 12 coronary bypass
      grafts, EBCT studies showed graft patency in 7 and occlusion in 5, as were
      confirmed by conventional graft angiography. CONCLUSION: EBCT angiography is a
      noninvasive method that could replace conventional coronary arteriography for
      CABG follow-up.

PMID- 10923509
TI  - [Microsurgical anatomy of far-lateral transcondylar approach].
AB  - OBJECTIVE: To supply the far-lateral transcondylar approach with some basic
      microsurgical anatomy and to protect vital structure. METHOD: We examined 10
      cadveric adult heads and 10 dry skulls. RESULTS: Mastoid process, jugular fossa,
      and occipital condyle were important signs. Inferior occipital triangle was
      formed by muscle rectus capitis posterior major, muscle oblique capitis superior,
      and muscle oblique capitus inferior, the important mark for distinguishing
      vertebral artery. Abdundant venous plexus around vertebral artery was the
      important bleeding source during operation. CONCLUSION: The aforementioned
      anatomic landmarks assist in localization, protection of vital structures.

PMID- 10923510
TI  - [Circulating ICAM-1 in sera of renal allograft recipients in monitoring of acute
      rejection].
AB  - OBJECTIVE: To study the significance of ICAM-1 in sera of renal allograft
      recipients in mornitoring of acute rejection. METHODS: The levels of circulating
      intercellular adhesion molecule-1 (cICAM-1) in sera of 87 renal transplantation
      recipients, including 29 patients with acute rejection and 8 patients with
      cyclosprine nephrotoxicity were measured by sandwich-ELISA. RESULTS: The levels
      of cICAM-1 were elevated transiently after transplantation. They decreased and
      reached normal levels within 2 weeks. In the acute rejection episode, the levels
      of cICAM-1 were significantly higher than those of patients with stable graft
      function and cyclosporine nephrotoxicity (P < 0.001). The increase of cICAM-1 was
      seen 1-3 days early than the diagnosis was made. On successful antirejection
      therapy, the levels of cICAM-1 decreased to normal, but in patients with steroid
      resistant rejection, it did not decrease. CONCLUSION: The cICAM-1 in sera can be
      used to estimate the graft function, and it is also useful in prediction and
      differential diagnosis of acute rejection and prognosis.

PMID- 10923511
TI  - [Auditory P300 in assessing cognitive dysfunctions of Alzheimer's disease and
      schizophrenia].
AB  - OBJECTIVE: To investigate the value of auditory P300 in assessing cognitive
      dysfunctions of aged patients with Alzheimer's disease(AD) or schizophrenia.
      METHODS: An'oddball' paradigm was used to elicit the auditory P300 from 39
      patients diagnosed as having Alzheimer's disease according to DSM-III-R, 34 aged
      schizophrenics and 40 normally age-matched subjects, by using a Dantec Concerto
      SEEG-16 instrument. RESULTS: The variability of P300 waveform increased in AD
      patients, who presented reduced N1 latency elicited by frequent stimuli. The P3
      amplitude of the AD patients was lowered by 14% compared with that of
      schizophrenics, and by 60% than compared with that of normal controls. Compared
      with the normal controls, schizophrenics presented reduced N1, P2, N2 and P3
      latencies, and their P3 amplitude was decreased by 54%. CONCLUSION: The auditory
      P300 is of value in assessing the cognitive dysfunctions of AD patients and aged
      schizophrenics.

PMID- 10923512
TI  - [Changes of plasma nitric oxide and endothelin levels in normal pregnant women
      and pregnancy induced hypertension].
AB  - OBJECTIVE: To investigate the relationship of nitric oxide (NO), endothelin-1 (ET
      1) levels and pregnancy induced hypertension (PIH). METHODS: 60 patients with
      PIH, 45 normal pregnant women and 15 normal non-pregnant women were studied.
      Plasma NO levels were determined. The stable metabolic product NO2-/NO3- of NO
      was letermined by Griess reaction. Plasms ET-1 levels were measured with
      radioimmunoassay. RESULTS: The NO2-/NO3- levels of the normal pregnancy group
      were significantly higher than those of the control group (P < 0.01),
      particularly in the second trimester of pregnancy. The NO2-/NO3- level of PIH was
      significantly lower in maternal plasma than that of the last trimester of normal
      pregnancy (P < 0.01) and nonpregnancy (P < 0.05), and it decreased with the
      disease development. In severe PIH the umbilical venous blood NO2-/NO3- level was
      significantly lower than that in the normal term pregnancy group (P < 0.01). The
      maternal plasma ET-1 level in PIH was significantly higher than that in the
      normal term pregnancy and control groups (P < 0.01). CONCLUSION: PIH might be
      related to decreasing synthesis and release of NO, and increasing ET-1
      production.

PMID- 10923513
TI  - [Hemangioblastomas of the central nervous system with von Hippel-Lindau's
      disease].
AB  - OBJECTIVE: To study the clinical features of hemangioblastomas of the central
      nervous system (CNS) when they occucr as a manifestation of von Hippel-Lindau's
      disease (HLD). METHODS: 174 patients with hemanioblastomas of CNS were reviewed
      from 1982 to 1995. All patients were verified pathologically. RESULTS: Ten of the
      patients definitely had HLD. Four patients reported a positive family history.
      Other 5 patients had retinal angiomas. The following lesions were detected: renal
      cysts(2 patients), renal tumor (1). Five patients were suspicous. CONCLUSION:
      Hemangio-blastoma may arise in isolation or as a manifestation of von Hippel
      Lindau's disease, and is often multiple in the latter. Enhanced MRI can decrease
      chances of negative diagnosis for tumor nodules. Microsurgery may be helpful to
      discover unclear lesions. Patients, especially those with HLD, should be
      subjected to follow-up and regular MRI examinations for a long time.

PMID- 10923514
TI  - [Expression of mdr-1 gene in cancer tissue and its association with morphological
      indexes of esophageal carcinoma].
AB  - OBJECTIVE: To detect the levels of mdr-1 gene expression in fresh untreated
      esophageal carcinomas, and to correlate these levels to current prognostic
      indicators of morphology. METHODS: mdr-1 gene expression of 46 untreated
      esophageal carcinoma was investigated with reverse transcription polymerase chain
      reaction (RT-PCR), and compared with the positive incidences among differentiated
      grades, TNM stages and macroscopic types of cancer. RESULTS: All 46 samples were
      pathologically squamous cell carcinoma. The positive incidence of mdr-1 gene
      expression was 37% (17/46) in the whole group, and 35% (6/17), 40% (8/20), 33%
      (3/9) for differentiated grade I, II and III respectively. The expression rate of
      33% (6/18), 40% (5/12), and 37% (6/16) was for TNM stage IIa, IIb, and III
      respectively. Macroscopically, the positive incidence was 37% (3/8) in
      constrictive, 33% (5/15) in fungating, 40% (6/14) in medullary, and 33% (3/9) in
      ulcerative type. There were no significant differences in each category system of
      morphology. CONCLUSION: Because of highly expressive level of mdr-1 gene in
      untreated esophageal carcinoma, we should choose appropriate chemotherapeutic
      regimen for esophageal Ca. The expression of mdr-1 gene in untreated esophageal
      cancer was independent of morphologic prognostic indexes without correlation
      between mdr-1 gene expression and morphological indexes.

PMID- 10923515
TI  - [In situ hybrid detection of p16 mRNA in primary breast carcinoma: its
      clinicopathologic significance].
AB  - OBJECTIVE: To investigate the expression of p16 mRNA in primary breast carcinoma
      and its clinicopathological significance. METHODS: In vitro transcriptional RNA
      probe labeled with biotin and in situ hybridization method were used in this
      study to detect p16 mRNA in the paraffin embedded tissue of human primary breast
      carcinoma from 120 cases. RESULTS: 85 breast carcinomas showed expression of p16
      mRNA with a positive rate of 70.8%. The p16 mRNA expression was not obviously
      correlated with patient age, tumor size, estrogen and progesterone receptor
      status (P > 0.05), but the positive rate of 54.4% for the lymph node metastasis
      group was significantly lower than 85.7% of the non-metastasis group (P < 0.001).
      Moreover, the positive rate of 58.3% for the poor differentiate invasive duct
      carcinoma was also lower than that 89.7% for the well differentiated (P < 0.05).
      The patients after operation were followed up. The mortality of 25% (21/85) in
      the p16 mRNA positive group was significantly lower than that of the negative
      group 57% (20/35) (P < 0.01). CONCLUSION: Abnormal expression of p16 mRNA may
      play an important role in the development of human breast carcinoma.

PMID- 10923516
TI  - [Magnetic resonance imaging with multiplane histomorphometry in avascular
      necrosis of femoral head: analysis of trabeculae].
AB  - OBJECTIVE: To distinguish the differences of changes of bone trabecular structure
      between high and low signal area which could directly reflect the mechanical
      strength and estimate the risk of collapse in avascular necrosis of femoral head
      (ANFH). METHODS: After total hip replacement, the specimen of ANFH was scanned by
      MR imaging. Accurate localization, consecutive slicing, multiplane
      histomorphometry, correspondence of MR images with slices were used. Mean
      trabecular width (MTW micron) and mean trabecular space (MTS micron) were
      selected as observation indexes. RESULTS: MTW in the low signal area was lower
      than that in the high signal area. MTS in the low signal area was higher than
      that in the high signal area. The results indicated that the dispersive degree of
      bone trabeculae was higher in the low signal area. CONCLUSION: Bone trabeculae in
      the low signal area necrosed and atrophied so that the bone volume and mechanical
      strength of trabeculae declined and bone trabeculae in the low signal area were
      liable to microfracture and collapse.

PMID- 10923517
TI  - [A primary study of transcranial magnetic stimulation (TMS)-induced muscle silent
      period(SP) in stroke patients with mild hemiparesis].
AB  - OBJECTIVE: To investigate the changes of muscle silent period (SP) induced by
      transcranial magnetic stimulation (TMS) and its value in the evaluation of motor
      function in patient with stroke. METHODS: 25 normals and 23 stroke patients with
      mild hemiparesis were involved in this study. A MES-10 magnetic stimulator and a
      9 cm round coil were used to stimulate the brain at an intensity 50% above
      threshold for MEP with the subjects making sustained moderate contraction of the
      contralateral FDI. SP duration and interside ratio were measured and calculated
      and then compared between the two groups. RESULTS: Normal values of SP duration
      and interside ratio were 145 +/- 37 ms and 1.01 +/- 0.15 respectively. The SP
      duration on the paralytic side in stroke patients was 423 +/- 314 ms,
      significantly prolonged in comparison with that on the normal side (154 +/- 54
      ms, P < 0.05) and that of normal value (P < 0.01). The interside SP ratio
      (paralytic/normal side) in stroke patients was 2.8 +/- 1.9, also significantly
      higher than the normal value (P < 0.01). CONCLUSION: SP might be a sensitive and
      valuable neurophysiological parameter in evaluation of the motor function of
      patients with central motor dysfunction.

PMID- 10923518
TI  - [Research reports in Chinese medical journals].
AB  - OBJECTIVE: To assess research designs employed in Chinese medical journals over
      the last decade. METHOD: The types of study design used in all original articles
      published in five leading journals (sponsored by the Chinese Medical Association)
      in 1985 (n = 640) and 1995 (n = 954) were evaluated. RESULTS: Of 1,594 articles,
      over 50% were case reports and cross-sectional studies, and one third were
      longitudinal studies. Compared with 1985, the proportion of clinical trials
      increased from 5.6% to 11.3%, especially that of RCT increased from 1.3% to 4.2%.
      The proportion of prospective studies also increased from 3.9% to 6.0% and that
      of retrospective studies decreased from 25.0% to 13.9%, particularly, that of
      case series decreased from 17.3% to 5.9%. The inappropriate use of research
      design was frequent, the proportion of this problem was 38.0% and 36.8% for 1985
      and 1995 respectively. The longitudinal studies were most liable to have this
      problem. The five commonly problems were the lack or inappropriateness of
      control, non-representativeness of sample, unbelievable conclusion, no
      randomization, and no consideration of confounders. They accounted for 66.9%.
      CONCLUSION: The quality of research designs used in Chinese medical research is
      gradually improving in the last decade, but the lack or inappropriate use remains
      a serious problem.

PMID- 10923519
TI  - [Enhancing the clinical study of rheumatoid arthritis].

PMID- 10923520
TI  - [Diagnostic criteria of persistent vegetative state in neurologic diseases].

PMID- 10923521
TI  - [Time selection for RA synovectomy].
AB  - OBJECTIVE: To discuss the time selection for RA synovectomy. METHOD: Eighty-six
      knees in 64 RA patients underwent synovectomy in 7 years. 8 of the 64 patients
      were in RA stage I, 26 in II, 24 in III, 8 in IV. The mean age was 43.9 years and
      the average follow-up period lasted 38.2 months. RESULTS: Pain relief and
      swelling reduction were significant clinical features after synovectomy. The
      overall assessment of the effect of synovectomy showed satisfactory results
      (72.9%) including all RA-I, and RA-II (87.2%). CONCLUSION: If the patients have
      sustained or intractable joint swollening with exuberant synovium after strict
      drug therapy over half a year, synovectomy is an appropriate consideration, it is
      very important to select the time for synovectomy.

PMID- 10923522
TI  - [Molecular analysis of HLA-DR beta polymorphism in Han nationality patients with
      rheumatoid arthritis].
AB  - OBJECTIVE: To analyze the molecular basis for HLA-DR associations with rheumatoid
      arthritis(RA) in the han nationality of Chinese population. METHODS: Polymerase
      chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques
      were used to dertermine DRB1 alleles in 35 unrelated patients with RA and 100
      healthy controls from the Han nationality. RESULTS: The frequency of DR4(DRB1 *
      04) was 51.4% in RA patients and 24.0% in the healthy controls(P < 0.01, RR =
      3.3). There was a significant increase in the presence of the amino acid
      sequences QKRAA or QRRAA both in the RA patients overall compared with the
      healthy group(65.7% vs 30.0%, P < 0.001) and in DR4+ RA patients compared with
      DR4+ healthy individuals(100% vs 75.0%, P < 0.05). Substitution of residues in
      QKRAA, V85 and G86 appeared to correlate with relative risk for RA, among the
      subjects having 0-1 amino acid substitution, RA occurred in 48.8%, whereas in
      subjects with 2-3 amino acid changes, RA was present in only 16.7%. CONCLUSION:
      These results suggest that DR4 is strongly associated with RA in the Han
      nationality, and the dominant effect that determines susceptibility to RA is
      associated with QKRAA or QRRAA as well as V85 and G86.

PMID- 10923523
TI  - [Rheumatoid arthritis synoviocyte hyperplasia and expression of fas and bcl-2
      genes].
AB  - OBJECTIVE: To determine whether apoptosis occurs in the proliferative synovial
      tissue and cells from patients with rheumatoid arthritis (RA). METHODS: In situ
      hybridization was carried out by using labeled RNA probes of fas, fasL, and bcl-2
      synthesized by in vitro transcription. Apoptosis was examined by DNA
      electrophoresis and flow cytometry. RESULTS: fas mRNAs were expressed in 6 of 7
      patients with RA. bcl-2 mRNAs were positive in 5 of 7 patients with RA. fasL
      mRNAs were not detectable in all the patients. bcl-2 mRNAs were always
      coexpressed with fas in RA synovial lining cells. The positive rates of fas and
      bcl-2 expression in RA synovial tissues were significantly higher than those of
      patients with osteoarthritis (OA) and normal synovial tissues (P < 0.05).
      Immunochemistry staining showed that Fas and Bcl-2 proteins were expressed in the
      synovial lining cells. Nucleic DNA extracted from the synovial tissues of 6
      patients with RA, 4 patients with OA and 2 normal controls. Agarose gel
      electrophoresis demonstrated that DNA ladders occurred in only one OA synovial
      tissue. The spontaneous apoptosis in cultured synoviocytes from patients with RA
      and OA was lower as analyzed by immunofluorescence staining and flow cytometry.
      CONCLUSION: The phenomena of apoptosis in RA synoviocytes was not significant and
      overexpression of bcl-2 perhaps inhibited apoptosis in these cells, leading to
      hyperplasia of RA synoviocytes.

PMID- 10923525
TI  - [Cloning and expressing of HCV NS5 partial gene and dynamic changes of anti-NS5].
AB  - OBJECTIVE: To study antigenicity of HCV NS5 protein and dynamic changes of anti
      NS5 in post-transfusion hepatitis C (PT-HC). METHODS: Epitopes of HCV NS5 protein
      were analyzed by Goldkey Program. NS5 gene fragment was amplified by reverse
      transcription and polymerize chain reaction (RT-PCR) from sera of PT-HC patients.
      Sequence analysis was performed, and recombinant strain was constructed. Series
      sera from PT-HC were detected for anti-NS5, ALT and HCV RNA. RESULTS: The
      homology of nucleotide and amino acid with genotype II in the same region was
      91.8% and 92.4%, respectively. SDS-PAGE analysis showed an expressing band around
      50 kD, the fusion protein represented about 21.4% of total bacterial protein.
      Western blot result proved the expressing band could specifically react with sera
      from hepatitis C patients. Detection results of series blood samples from PT-HC
      showed that the antibody against NS5 appeared relatively late, the positive
      conversion time was 182.9 +/- 168.5 day. Dynamic changes of anti-NS5 were
      correlated with serum ALT in most cases. The types of dynamic change of anti-NS5
      were passing positive; intermittent positive; persistent positive, and persistent
      negative in two years. CONCLUSION: Antibody against NS5 may reflect the disease
      activity to some extent. It appears relatively late, and is of no value in early
      stage diagnosis.

PMID- 10923524
TI  - [Effect of ganglioside GM1 on the metabolism of Alzheimer amyloid beta-protein
      precursor].
AB  - OBJECTIVE: To study the effect of GM1 ganglioside interfering the metabolism of
      amyloid beta-protein precursor (APP) on cells for exploring the relationship
      between GM1 and development of Alzheimer senile plaques and the other
      amyloidoses. METHODS: GM1 influencing the metabolism of APP and the release of
      its metabolite secretory APP on human APP695 cDNA transfected cells were detected
      by metabolic radiolabeling. The affinity of GM1 and recombinant secretory APP was
      analyzed by Western blot and dot blot. RESULTS: GM1 specifically bound APP, and
      interfered the proteolysis of APP and inhibited the release of secretory APP on
      cells. CONCLUSION: The abnormal metabolism of GM1 may contribute to the
      aggregation and deposition of amyloid beta-protein in Alzheimer brains.

PMID- 10923526
TI  - [A survey on the physical growth of children under 7 years in the urban and
      suburban rural areas of nine cities of China in 1995. Coordinating Group of Nine
      Cities on Physical Growth and Development of Children].
AB  - OBJECTIVE: To know the changing trend of physical growth of Chinese children and
      compare their nutritional status with that of ten years ago. METHODS: Random
      cluster sampling was used and 157,362 healthly children were classified into 22
      groups according to location (urban and rural), sex(boy and girl), and age (0-7
      years). RESULTS: As compared with the results in 1985, the mean weight, height
      and sitting height were significantly increased. The chest and head circumference
      in most age groups were slightly improved. The urban-rural difference in weight
      and height reduced. The children in northern and central china were heavier and
      taller than those in southern China though the regional gap is narrowing in this
      respect. CONCLUSION: The condition of growth and nutrition of children 0-7 years
      from urban and suburban rural areas has been much improved. The growth speed of
      rural children has caught up or surpassed that of their urban peers.

PMID- 10923527
TI  - [Preoperative localized diagnosis of insulinoma by aterial stimulating and venous
      sampling methods].
AB  - OBJECTIVE: To establish a method for bocative diagnoses of insulinoma, METHOD:
      Five patients with insulinoma were given locative diagnoses by using ASVS methods
      which mean injecting calcium stimulatant into pancreatic supplying arteries and
      then taking blood specimens from henatic vein to gauge the insulin levels. Six
      samples, each 2 ml, were taken before and 30, 60, 90, 120, 180 seconds after the
      injection. RESULTS: If the peak of blood-insulin level was twice or higher than
      the basic level, the tumor was located in the domain. These results were
      confirmed operatively in all the five cases. CONCLUSION: ASVS is an accurate
      technique to localize insulinoma.

PMID- 10923528
TI  - [Blood supply reestablishment of avascular necrosis of femoral head with digital
      subtraction angiography].
AB  - OBJECTIVE: To use digital subtraction angiography (DSA) to evaluate blood supply
      reestablishment after the treatment of the avascular necrosis of femoral head
      (ANFH) by using the vascularized iliac periosteum with deep iliac circumflex
      artery (DICA) and vein pedicle. METHODS: Seldinger method was used to puncture
      femoral artery interpate of 20 patients with pre and postoperative ANFH. 6.5 F
      Cobrn conduct was optionally used and put directly into DICA and then contrast
      medium, was injected for observation of blood vessel. RESULTS: Before operation,
      the position of DICA was found constant, 3 to 7 branches termity among the crest
      part of iliac bone. Three weekes after operation, DICA was found wider than that
      before operation, but the blood flow speed remained almost the same and its
      termity was distributed evenly inside the femoral head and looked like a bird's
      net. Three months after operation, the blood vessel was still wider, but blood
      flowed faster and its termity changed roundish, and the bird's net changed
      greatly and capillaries reached the subchoronal zone of femoral head. CONCLUSION:
      Blood flow was well reestablished after the treatment of ANFH by DSA. It can be
      easily checked with less damage, large liability, and clear picture.

PMID- 10923529
TI  - [The analysis of the causes of postoperative deaths in intracranial meningiomas
      in the elderly department of neurosurgery].
AB  - OBJECTIVE: Analysis the postoperative death reason of elderly patients with
      meningioma. METHOD: We analysised the death reason of 18 elderly patients with
      meningioma who died after operation in recent 16 years, Reviewing of document is
      also included in this review study. RESULT: 7 patients died of postoperative
      cerebral infarction (3 cases sufferd heamorrage of gastric-instinal tract). 3
      cases died of cardiac infarction. 2 cases renal failure and 2 cases preoperative
      cerebral hernia. 1 case inhalant pneumonia, 1 case postoperative cerebral
      hematoma, 1 case hypothamamus injury and 1 case respiration failure. CONCLUSION:
      Operation is not prompt to patients whose KS scale is less than 50.

PMID- 10923531
TI  - [Esophageal carcinoma in part of population of Yangquan City].
AB  - OBJECTIVE: To evaluate the contribution of genetic factors to the occurrence of
      esophageal carcinoma (EC). METHODS: A genetic epidemiology survey of one-tenth of
      the whole population (130,000 people) was conducted in 6 towns of Yangquan City,
      Shanxi province in 1994. 228 high-risk (EC) families were matched with equal
      number of control families. RESULTS: The heritability of EC among first grade
      blood relatives was 52.6%, that among second grade blood relatives was 31.2%, and
      the summing up powered heritability was 49.2%. the segregation ratio was 18 +/-
      3%, far less than 25%, suggesting a multi-gene effect. The distribution of EC in
      families did not fit well the binomial distribution, suggesting familial
      aggregation. The relative risk among male first grade blood relatives was 10.49,
      female was 7.69, in sum was 9.17. The attributive risks (AR) among first grade
      blood relatives were 62.13/100,000(male), 99.14/100,000(female) and
      75.15/100,000(total). All of these figures were higher than the average
      (40.17/100,000). CONCLUSION: Genetic factors plays important roles in occurrence
      of EC in the Taihang mountain region.

PMID- 10923530
TI  - [The effect of amlodipine, nifedipine and perindopril on insulin sensitivity and
      blood lipid of patients with essential hypertension].
AB  - OBJECTIVE: To investigate the effect of amlodipine, nifedipine and perindopril on
      insulin sensitivity(IS) and blood lipid of patients with essential
      hypertension(EH). METHODS: 105 EH patients were randomly divided into 3 groups:
      amlodipine group; nifedipine group; perindopril group. Treatment period lasted
      for 4 weeks. Before and after treatment, IS was measured by euglycemic insulin
      clamp technique with glucose metabolism rate (M) as an index of IS. RESULTS:
      Amlodipine, nifedipine and perindopril significantly reduced blood pressure
      compared with that before treatment(P < 0.01). In the EH patients with decreased
      IS, the M value (mg.kg-1.min-1) after the use of amlodipine, nifedipine and
      perindopril was higer than that before treatment (amlodipine: 6.6 +/- 1.5 Vs 4.6
      +/- 0.6, P < 0.01; nifedipine: 5.2 +/- 1.2 Vs 4.4 +/- 0.6, P < 0.05; perindopril:
      6.8 +/- 1.6 Vs 4.4 +/- 0.6, P < 0.01). The increase of M value(mg.kg-1.min-1),
      nifedipine (1.2 +/- 0.9) were significantly lower than that of amlodipine(2.1 +/-
      1.1) and perindopril(2.4 +/- 1.5), P < 0.01, respectively, but no significant
      difference was found between amlodipine and perindopril(P > 0.05). CONCLUSION:
      Amlodipine and perindopril have beneficial effect on improving insulin
      sensitivity in EH patients with decreased insulin sensitivity. The effect of
      nifedipine on insulin sensitivity is lower than that of amlodipine and
      perindopril. Blood lipid is not significantly changed after short treatment.

PMID- 10923532
TI  - [Telomerase activity in gastric cancer and premalignant lesions: determination
      and its clinical significance].
AB  - OBJECTIVE: To evaluate the role of telomerase activity in the development and
      progression of gastric cancer (GC) and if knowedge of telomerase activity may be
      an indicator for the early diagnosis and poteneial treatment of GC. METHODS:
      Using PCR-based TRAP (telomeric repeats amplification protocol) assay, we
      examined telomerase activity in 176 samples of gastric mucosa. Meanwhile, some
      tumor tissues were also analyzed by serial dilution. RESULTS: Telomerase activity
      detected in chronic atrophy gastritis (CAG), intestinal metaplasia (IM);
      dysplasia (Dys); and gastric cancer (GC) was 24.6% (14/57), 38.9% (7/18), 37.5%
      (3/8), and 92.3% (60/65) respectively; which was significantly higher than that
      in normal tissues (NT) (P < 0.01-0.05). Telomerase activity in group of GC was
      also significantly higher than that in group of CAG, IM and Dys (P < 0.01).
      Frequencye and levels of telomerase activity were not associated with patients'
      sex, tumor location, size gross type, depth of invasion, lymph node metastases,
      differentiation and clinical stage. CONCLUSION: Telomerase activity is detected
      not only in GC tissues, but also in some premalignant lesions or diseases.

PMID- 10923533
TI  - [Frequency of protein C polymorphisms in Chinese population and thrombotic
      patients].
AB  - OBJECTIVE: To study the allelic frequencies of protein C(PC) polymorphisms in
      Chinese Han population and thrombotic patients. METHODS: Two PC polymorphisms PC
      1476A/T and PC3342T/G situated in exon 1 and exon 6 of PC were detected by PCR
      SSCP silver stain. Ninty normal individuals and 105 patients with thrombosis were
      studied. RESULTS: The frequencies of PC-1476A/T in normal individuals were
      obviously different from in Caucasians (0.867/0.133, 0.4/0.6), whereas the
      frequencies of PC-3342T/G were similar in Chinese and Caucasians (0.60/0.40,
      0.59/0.41). The frequency distributions of the two polymorphisms were consistent
      with the law of Hardy-Weinberg and were in the mode of linkage disequilibrium.
      The frequences of rare alleles PC-1476T and PC-3342G were higher in thrombotic
      patients (0.21 and 0.46) than in normal controls (0.13 and 0.40). PC-1476T was
      especially high in CHD patients (0.243) (P < or = 0.05). CONCLUSION: These
      results suggest that the two polymorphisms may be one of the genetic related
      factors in venous and arterial thrombosis.

PMID- 10923534
TI  - [Pathological analysis of 180 cases of cerebrovascular disorder in autopsy].
AB  - OBJECTIVE: To evaluate the ratio of each kind of causes in 180 cases of
      cerebrovascular disorder(CVD) in autopsy. RESULTS: In 180 cases of CVD in
      autopsy: (1)125 (69%) belong to brain hemorrhage including hypertension 36
      cases(20%), vascular malformation 28 cases(16%), hemopoitic diseases and blood
      coagulation disturbances 23 cases(13%), congenital aneurysm and brain tumor 9
      cases(5%) each separately. (2) 55 cases (31%) are due to brain infarction, main
      of them are caused by embolism 29 cases (16%) and thrombosis 17 cases(10%).
      Thrombosis related to atherosclerosis has 5 cases(3%). CONCLUSION: In CVD in
      autopsy, brain hemorrhage is more than infarction, the ratio of them is 2.3:1.
      More than 50% of cases is due to hypertension and vascular malformation. In
      infarction, embolism is more than thrombosis, the ratio of them is 1.7:1.
      Vascular malformation is more than congenital aneurysm, the ratio of them is 3:1.

PMID- 10923535
TI  - [Detecting cytokines in patients with preterm premature rupture of membrane].
AB  - OBJECTIVE: To study the relationship of maternal blood and amniotic fluid
      cytokine levels in patients with preterm premature rupture of membrane and
      chorioamnionitis. METHODS: IL8 and TNF alpha levels of maternal blood and
      amniotic fluid were determined by 125I radioimmunoassay (RIA) and an enzyme
      labeled immunosorbent assay (ELISA). Chorioamnionitis was diagnosed by fetal
      membrane histology. RESULTS: The maternal serum IL8 levels and amniotic fluid
      IL8, TNF alpha levels were higher than those of controls (P < 0.05). There was
      significant relationship between maternal serum and amniotic fluid IL8, TNF alpha
      with the time of the premature rupture of membanes. The longer the time the
      higher the maternal serum IL8 and amniotic fluid IL8, TNF alpha; There were 13
      patients with chorioamnionitis, and their maternal serum and amniotic fluid IL8,
      TNF alpha were higher than those of patients with non-chorioamnionitis (P < 0.01
      0.05). CONCLUSION: IL8, TNF alpha levels of maternal serum and amniotic fluid are
      valuable clinical indexes in identification of chorioamnionitis in patients with
      preterm premature rupture of membranes.

PMID- 10923536
TI  - [Identification of interleukin-1 beta converting enzyme gene expression in human
      kidney].
AB  - OBJECTIVE: To confirm that Interleukin-1 beta-converting enzyme(ICE) is a first
      identified apoptosis related gene in mammals. METHODS: The expressions of ICE
      mRNA in human kidney tissue, different segment of nephron and glomerular resident
      cells were measured by using the method of microdissection, reverse transcription
      polymerase chain reaction(RT-PCR) and Northern hybridization. RESULTS: Compared
      with peripheral blood mononuclear lymphocyte weak expressions of ICE mRNA were
      noted not only in glomeruli and tubule but also in glomerular mesangial cells,
      glomerular endothelial cells and tubular epithelial cells of the human kidney.
      CONCLUSION: There is a widely distributed expression of ICE mRNA in the human
      kidney, which may provide a theoretical basis for the study of ICE gene in
      apoptosis of kidney.

PMID- 10923537
TI  - [Idiopathic interstitial nephritis induced acute renal failure: clinical and
      pathological analysis].
AB  - OBJECTIVE: To understand idiopathic interstitial nephritis (IIN) and its
      relationship with acute renal failure as well as its clinical and pathological
      characteristics for avoiding misdiagnosis and missing diagnosis. METHOD: A detail
      clinical and pathological analysis was performed on 7 patients with idiopathic
      interstitial nephritis. RESULTS: The major manifestations were acute non-oliguric
      renal insufficiency combined with mild proteinuria (< 2 g/d), microscopic
      hematuria and obvious disorder of renal tubular function (for example,
      glycosuria). Three patients had high gamma-globulinemia and 2 were associated
      with uveitis. Renal biopsy showed typical tubulointerstial nephritis but
      glomeruli, and the renal vasculature was almost normal. All patients were treated
      with prednison. Renal function recovered in 5 patients. CONCLUSION: When a
      patient has renal insufficiency especially non-oliguric renal failure with
      disorder of tubular function without definite causes, IIN should be considered.
      The diagnosis and treatment should be done immediately.

PMID- 10923538
TI  - [Mechanism and treatment of malignant glaucoma].
AB  - OBJECTIVE: To investigate the possible mechanism and the treatment of malignant
      glaucoma. METHODS: The onsets of 34 eyes in 23 cases of malignant glaucoma were
      analyzed and the patients were treated with medicine, lens extraction,
      vitrectomy, anterior chamber plastic operation or combined procedures. RESULTS:
      The effective rate in medical treatment was 35.3%. Combined procedures (lens
      extraction associated with vitrectomy and anterior chamber plastic operation)
      were all successful. CONCLUSIONS: The possible mechanism of malignant glaucoma
      may be concerned with the formation of membranoid substance among vitreous face,
      ciliary body and posterior iris. Those who failured to medical therapy and were
      treated with combined operations may have good effect.

PMID- 10923539
TI  - [Antisense N-ras1 gene inhibits the proliferation of VSMC induced by bFGF after
      arterial injury].
AB  - OBJECTIVE: To develop a new way to prevent the process of restenosis after
      arterial injury, we transfer the recombinant antisense N-ras1 gene to the
      cultured SMCs and studied the influence of gene therapy with antisense N-ras1 on
      the SMCs proliferation induced by bFGF. METHODS: With the recombinant antisense N
      ras1 plasmids (fpGv1-MT-N-ras1) transfered to the cultured SMC, we studied the
      effect on the SMCs proliferation induced by bFGF. RESULTS: The results of the
      experiment indicated that the count of cells transfered antisense N-ras1 was 16.8
      +/- 1.3 x 10(4), the control cells transfered fpGv1-MT retrovirus vector were
      30.1 +/- 1.2 x 10(4) (cell/ml) (P < 0.001). cell [3H] thymedine incorporation was
      7,643 +/- 672 cpm in gene therapy cells, and 15,131 +/- 138 cpm in vector control
      cells (P < 0.001). Gene therapy cells ras mRNA and p21 were significantly
      decreased by Northern blotting and Western blotting technique. CONCLUSION: These
      results suggest that antisense N-ras1 gene may inhibit the proliferation of
      cultured VSMC induced by bFGF.

PMID- 10923540
TI  - [Current use of statistical methods in five core Chinese medical journals].
AB  - OBJECTIVE: To determine the frequency of statistical techniques used in Chinese
      medical journals, types of statistical errors present, and trends over a 10-year
      period. METHODS: We reviewed the statistical methods used in all original
      articles published in 5 leading journals in 1985 (n = 640) and 1995 (n = 954).
      RESULTS: Compared with 1985, significant improvement was seen in 1995. The
      proportion of papers using statistical tests increased from 40% to 60% (chi 2 =
      60.9, P < 0.01), and more sophisticated statistical methods were used. Of those
      articles using statistics, the proportion using appropriate methods increased
      from 22% to 46% (chi 2 = 45.3, P < 0.01). In both years, the most commonly used
      statistical methods were t tests and contingency tables. The most common errors
      were presentation of P values without specifying the test used, use of multiple t
      tests instead of ANOVAs, and use of unpaired t tests when paired tests were
      required. CONCLUSION: The use of statistical methods in Chinese medical journals
      is improving, and by 1995, the frequency of using statistical methods in
      published articles was similar to that in other journals around the world.
      However, the lack of or inappropriate sue of statistics remains a serious
      problem.

PMID- 10923541
TI  - [Mechanism of antimicrobial resistance in Gram-positive bacteria and its
      therapeutic tactic].

PMID- 10923542
TI  - [Progress on the study of ob gene].

PMID- 10923543
TI  - Is a single oral dose of amiodarone safe and effective in converting new-onset
      atrial fibrillation (AF) to sinus rhythm?

PMID- 10923545
TI  - Does oral metronidazole prevent preterm delivery in normal-risk pregnant women
      with asymptomatic bacterial vaginosis (BV)?

PMID- 10923544
TI  - In patients with stable persistent asthma, can lower doses of inhaled
      corticosteroid medication control symptoms and maintain optimal pulmonary
      function as well as high doses?

PMID- 10923546
TI  - Are there differences between vasodilating and nonvasodilating beta-blockers in
      patients with heart failure? Do patients with ischemic heart disease benefit to
      the same degree?

PMID- 10923547
TI  - Do foot examinations reduce the risk of diabetic amputation?
AB  - BACKGROUND: Foot examinations are widely recommended as a means to reduce
      amputation risk, but no investigators have studied their independent effect on
      this outcome. METHODS: We conducted a population-based case-control study of
      primary care provided to Pima Indians from the Gila River Indian Community. Sixty
      one Pima Indians with type 2 diabetes and a first lower-extremity amputation
      between January 1, 1985, and December 31, 1992, were compared with 183 people who
      had no amputation by December 31, 1992. The type of foot examination conducted,
      comorbid conditions, and foot risk factors present in the 36 months before the
      pivotal event were abstracted from medical records. All ulcer care was excluded.
      The independent effect of foot examinations on the risk of amputation was
      assessed by logistic regression. RESULTS: During the 36 study months, 1857 foot
      examinations were performed on 244 subjects. The median number of preventive foot
      examinations was 7 for case patients and 3 for control patients. After
      controlling for differences in comorbid conditions and foot risk conditions, the
      risk of amputation for persons with 1 or more foot examinations was an odds ratio
      (OR) of 0.55 (95% confidence interval [CI], 0.2-1.7; P=.31). The risk of
      amputation associated with written comments of nonadherence with therapeutic foot
      care recommendations or diabetic medication was an OR of 1.9 (95% CI, 0.9-4.3;
      P=.10). CONCLUSIONS: Our study failed to demonstrate that foot examinations
      decrease the risk of amputation in Pima Indians with type 2 diabetes. However,
      foot examinations detect high-risk conditions for which specific interventions
      have been shown to be effective in reducing amputation risk.

PMID- 10923548
TI  - Judging the evidence for interventions. Asking the right questions about foot
      examinations for patients with diabetes.

PMID- 10923549
TI  - Barriers to communication about diabetes mellitus. Patients' and physicians'
      different view of the disease.
AB  - BACKGROUND: Management of diabetes mellitus is difficult for both the patient and
      the clinician, and poor communication resulting from different conceptions of the
      disease and different treatment goals can exacerbate the problem. METHODS: We
      used qualitative methods, including semistructured interviews with patients and
      clinicians and direct observation of clinical precepting sessions by trained
      observers at an inner-city family practice training site. Transcripts from these
      sessions were analyzed for content (with the help of Nud.ist software) to
      identify themes that highlight problem areas in clinician-patient communication.
      RESULTS: The most important themes revolved around the concept of control, which
      was used in at least 3 different ways, and the concept of frustration.
      Frustration resulted from different understandings of the biology, physiology,
      and natural history of the disease, and approaches to treatment. In the
      interviews, clinicians often spontaneously acknowledged the multiple physical,
      psychological, and social obstacles to treatment confronted by their patients,
      but in observed practice they almost always focused entirely on managing blood
      sugar numbers. CONCLUSIONS: Different conceptions of the term "control" affect
      the ability of patients and clinicians to communicate effectively. The tendencies
      of clinicians to view their own management strategy as scientific truth, and
      their focus on managing numbers rather than attempting to understand their
      patient's conception of disease and their treatment goals, lead to frustration
      and are serious obstacles to effective collaboration.

PMID- 10923550
TI  - Diabetes care as public health.

PMID- 10923551
TI  - Intrathecal narcotics are associated with prolonged second-stage labor and
      increased oxytocin use.
AB  - BACKGROUND: Safe and effective labor analgesia is an important part of obstetric
      care. Intrathecally injected narcotics (ITN) are an effective alternative to
      epidural anesthesia, and are perceived less likely to interfere with the course
      and outcome of labor. Data on their effects, however, are sparse and
      contradictory. METHODS: Our retrospective study compared labor length, oxytocin
      use, delivery type, maternal side effects, and neonatal outcomes among women who
      received ITN (n=100) and a group who received intravenous narcotics or no
      analgesia during labor (n=100). We randomly sampled medical records with
      stratification for parity and collected data through systematic chart review.
      RESULTS: Women receiving ITN were more likely to be white. They experienced
      longer second-stage labors (73 minutes vs 40 minutes, P=.000) and used oxytocin
      twice as often. These differences remained significant after controlling for
      potential confounding factors. ITN use was also associated with a trend toward
      more cesarean sections (7% vs 1%, P=.06). More of the women receiving ITN
      required urinary catheterization (25% vs 5%, P=.000) and experienced significant
      pruritus (10% vs 0%, P=.001). Neonatal outcomes were similar for both groups.
      CONCLUSIONS: In our retrospective study, ITN use was associated with a
      significant prolongation of second-stage labor, which may be clinically relevant
      for women having their first child. ITN were also associated with increased
      oxytocin use and a trend toward more cesarean births. Whether these relationships
      are causal or a proxy for more difficult labors is a question for future
      prospective studies.

PMID- 10923552
TI  - Remission of alcohol disorders in primary care patients. Does diagnosis matter?
AB  - BACKGROUND: Alcohol use disorders (AUDs) are prevalent in primary care patient
      populations. Many primary care patients with AUDs can remit without formal
      treatment. An understanding of the factors that predispose patients to remission
      may help primary care physicians provide effective brief counseling for those
      with mild to moderate disorders and more effectively recommend formal treatment
      for others. METHODS: A total of 119 eligible and randomly selected primary care
      patients with alcohol abuse or dependence in remission (as defined in Diagnostic
      and Statistical Manual of Mental Disorders, third edition, revised) participated
      in a semistructured telephone interview. RESULTS: Of the subjects, 59.7% were
      women; 50.4% had been alcohol dependent; 66.3% made a conscious decision to
      modify their drinking; and 62.1%, including 54.2% of the alcohol-dependent
      subjects, moderated their drinking without abstaining. Family, emotional, and
      medical issues most often prompted reduced drinking. Nearly one third of the
      subjects found specific strategies and rules helpful in reducing their drinking,
      and many cited circumstances that helped or hindered their efforts. Only 10.9%
      had formal alcohol treatment. CONCLUSIONS: A significant proportion of patients
      with AUDs remitted without formal treatment. Abstinence may not be necessary for
      a subset of dependent patients. When counseling patients with active AUDs,
      primary care clinicians are advised to counsel patients about the psychosocial
      and medical reasons to control drinking, promote rule-setting about drinking,
      help patients avoid circumstances that trigger drinking, and support patients'
      attempts at moderating drinking rather than abstaining. Motivational interviewing
      (motivational enhancement therapy) may provide a useful framework for such
      counseling.

PMID- 10923553
TI  - Predictors of anticipated breastfeeding in an urban, low-income setting.
AB  - BACKGROUND: Although the proportion of women who breastfeed is known to vary by
      demographic group, breastfeeding practices have not been sufficiently studied
      among urban, lower income African American populations seen in family medicine
      centers. METHODS: A cross-sectional design was used to examine demographic,
      clinical, and attitudinal factors that affect anticipated infant feeding
      practices reported by postpartum women from a low-income, urban family practice
      setting. Data was analyzed using chi-square, odds ratios (OR), and multiple
      logistic regression techniques. RESULTS: Among 66 respondents, only 3 subjects
      (4.5%) indicated that they planned to breastfeed exclusively, while an additional
      11 subjects (16.7%) reported plans to use a combination of bottle-feeding and
      breastfeeding. Based on univariate analyses, women with less than 12 years of
      education were less likely to report anticipated breastfeeding. Otherwise,
      breastfeeding plans were not associated with subject demographic features or with
      reproductive characteristics. Respondents planning to bottle-feed noted that
      breastfeeding was too complicated. Logistic regression demonstrated an inverse
      relationship between level of maternal education and anticipated breastfeeding
      (OR=0.13, 95% confidence interval [CI], 0.05-0.35), and a direct association for
      encouragement from the baby's father or the woman's mother to breastfeed and
      anticipated breastfeeding (OR=12.4; 95% CI, 4.92-31.4). CONCLUSIONS: This study
      reports unique data regarding anticipated infant feeding practices among patients
      from an urban, low-income community served by a family medicine center. Findings
      from this study will be used to develop a family-centered educational
      intervention involving the mothers, grandmothers, and partners of pregnant
      patients to promote the benefits of breastfeeding in this community.

PMID- 10923554
TI  - Does a family physician who offers colposcopy and LEEP need to refer patients to
      a gynecologist?
AB  - BACKGROUND: Many family physicians perform colposcopy and provide treatment when
      biopsy reveals dysplasia. Before the adoption of loop electrical excision
      procedure (LEEP) gynecologic referral following colposcopy was required for a
      small percentage of women--most commonly for cold cone procedures. The use of
      LEEP and LEEP cones may obviate the need for cold conization, so we sought to
      assess the pattern of gynecologic referral in the practice of family physicians
      skilled in this procedure. METHODS: We reviewed the referral practices of a
      family medicine residency practice that routinely provides LEEP for biopsy-proven
      cervical intraepithelial neoplasia requiring treatment. Colposcopy and, when
      indicated, LEEP were performed primarily by the senior author or by residents
      under close faculty supervision. The computerized clinic log was reviewed for all
      patients from its 1993 inception through November 1999, and all treatment
      decisions were evaluated. RESULTS: During the study period, 283 women were seen
      in the clinic, and 26 individuals (9%) were referred by the family physician
      colposcopist to a consulting gynecologist. CONCLUSIONS: Despite use of LEEP, a
      minority of patients continues to need gynecologic referral. Large acetowhite
      lesions extending onto the vaginal fornix accounted for the majority of
      referrals, and some patients were referred exclusively for cold cone biopsy.
      Although LEEP can allow family physicians to manage cases previously requiring
      referral, we urge that this procedure be employed only by those with the
      technical and decision-making skills required for safe and effective treatment.

PMID- 10923555
TI  - The rate of hydrocele perforation during vasectomy. Is perforation dangerous?
AB  - BACKGROUND: Hydroceles are not uncommon, are often occult, and may be associated
      with an inguinal hernia. The rate of hydrocele perforation during elective
      vasectomy has not been reported in the medical literature. Our objective was to
      estimate the frequency and consequences of hydrocele perforation incidental to
      vasectomy. METHODS: We retrospectively reviewed data from a series of patients
      undergoing vasectomy using the no-scalpel technique for the incidence of
      complications. A supplementary chart review was done to determine preoperative
      conditions, and telephone contacts were made if needed to assess later morbidity.
      RESULTS: We noted 7 perforations in 150 vasectomies. Only one patient had a
      hydrocele documented preoperatively. Three had histories of inguinal hernia and
      herniorrhaphy. Five patients had evidence of minor swelling early on, but none
      had additional morbidity or long-term associated complications. CONCLUSIONS: This
      small case series of vasectomies had a 4.7% incidence rate of perforated small or
      occult hydroceles. Physicians should be aware of this potentially alarming but
      apparently minor phenomenon that may accompany vasectomy.

PMID- 10923556
TI  - Physicians' advice to quit smoking. The glass remains half empty.
AB  - BACKGROUND: We explored the relationships between advice from a physician to quit
      smoking and an array of respondents' characteristics, including sociodemographic
      factors, health status, health insurance status, physician continuity, and
      intensity of smoking. METHODS: We examined data from the nationally
      representative 1996-1997 Community Tracking Study Household Survey. We used
      multivariate logistic regression to model receipt of cessation advice in a sample
      of 8229 smokers aged 18 years and older who made at least one visit to a
      physician in the past year. RESULTS: Less than 50% of the subjects reported
      receiving cessation advice. Advice was less likely for patients who were younger,
      men, African American, uninsured, healthier, lower health care services users, or
      lighter smokers, and more likely for those with military health insurance, who
      attended hospital outpatient clinics, or who belonged to health maintenance
      organizations. CONCLUSIONS: Physicians continue to miss opportunities to provide
      smoking cessation advice, a potentially lifesaving intervention. Given the
      adverse health consequences of tobacco use and the demonstrated benefit of advice
      to quit, physicians need to improve their cessation counseling efforts.

PMID- 10923558
TI  - Can addressing family relationships improve outcomes in chronic disease? Report
      of the National Working Group on Family-Based Interventions in Chronic Disease.
AB  - The management of patients with chronic disease constitutes the largest single
      cost to the health care system in the United States. New approaches and methods
      are needed to reduce preventable complications and to enhance the health and well
      being of patients with chronic disease and their families. Interventions that
      target the family setting in which disease management takes place have emerged as
      an alternative to traditional strategies that focus only on the individual
      patient or that consider the family only as a peripheral source of positive or
      negative social support. In this approach, the educational, relational, and
      personal needs of all family members are emphasized. Data reviewed by the
      National Working Group on Family-Based Interventions in Chronic Disease
      identified potential mechanisms by which the relational context of the family
      affects disease management and how characteristics of family relationships serve
      as risk or protective factors. In this paper we describe the major forms of
      family-based interventions, review the results of selected clinical trials, and
      present applications for clinical practice. The data suggest that approaches to
      the management of chronic disease should be expanded to include the broader
      relational context in which disease management takes place. Although it adds
      complexity to clinical intervention, this approach increases clinical
      flexibility, addresses the important players in disease management, and accounts
      for a significant number of risk and protective factors that affect outcome.

PMID- 10923557
TI  - A systematic review of troponin T and I for diagnosing acute myocardial
      infarction.
AB  - OBJECTIVE: Elevations of serum troponin T and I values are being used to diagnose
      acute myocardial infarction (AMI) and to rule out the condition in patients
      before their discharge from the emergency department (ED). However, the
      sensitivity and specificity of these tests vary considerably. Our goal was to
      systematically review the data on the accuracy of troponin T and I for the
      diagnosis of AMI in the ED. SEARCH STRATEGY: We searched the MEDLINE database
      using the following strategy: troponin (text word) and diagnosis (medical subject
      heading [MeSH]) or troponin/diagnostic use (MeSH). The references of articles
      meeting our inclusion criteria were searched for additional articles. SELECTION
      CRITERIA: We evaluated each study for quality. Only prospective blinded cohort
      studies with an adequate reference standard were included in the analysis. DATA
      COLLECTION/ANALYSIS: Data from each study were abstracted by 2 investigators. We
      graphed sensitivity and specificity for different points in time from arrival in
      the ED or from the onset of pain and calculated summary estimates when
      appropriate and possible. MAIN RESULTS: Sensitivity increases for both troponin T
      and I from 10% to 45% within 1 hour of the onset of pain (depending on the
      cutoff) to more than 90% at 8 or more hours. Specificity declines gradually from
      87% to 80% from 1 to 12 hours after the onset of chest pain for troponin T and is
      approximately 95% for troponin I. The peak abnormal value in the first 24 hours
      after admission to the ED has an area under the receiver operating characteristic
      curve of 0.99 and is very useful at ruling out AMI if negative. CONCLUSIONS:
      Although troponin T and I values are useful tools for the diagnosis of AMI, they
      must be interpreted according to the number of hours from the onset of chest
      pain. The test is particularly useful at ruling out MI when the value is negative
      at 8 or more hours after the onset of chest pain.

PMID- 10923559
TI  - Are glucosamine and chondroitin effective in treating osteoarthritis?

PMID- 10923560
TI  - What is the long-term efficacy and tolerability of orlistat, a gastrointestinal
      lipase inhibitor, for the treatment of obesity in primary care?

PMID- 10923561
TI  - Is a 7-day course of ciprofloxacin effective in the treatment of uncomplicated
      pyelonephritis in women?

PMID- 10923562
TI  - Is a 3-day hospitalization cost-effective for patients after uncomplicated acute
      myocardial infarction (AMI)?

PMID- 10923563
TI  - I won't ask him about that.

PMID- 10923564
TI  - How effective is doxazosin compared with chlorthalidone in the treatment of
      hypertension?

PMID- 10923565
TI  - Can low-dose aspirin prevent thromboembolic phenomena in patients undergoing
      surgery for hip fracture or elective arthroplasty?

PMID- 10923566
TI  - What is the protective effect of previous coronary artery bypass graft compared
      with percutaneous transluminal coronary angioplasty in patients with diabetes who
      suffer an acute myocardial infarction?

PMID- 10923567
TI  - Does carotid endarterectomy benefit patients with carotid stenosis but no
      symptoms?

PMID- 10923568
TI  - The maternal perspective on prenatal ultrasound.
AB  - BACKGROUND: Most women in the United States will have a routine sonogram during
      pregnancy. The medical necessity of this is debatable. The goal of our study was
      to examine maternal beliefs about prenatal sonography. METHODS: We surveyed 150
      prenatal patients at their point of entry to maternity care at a large military
      medical center. The main outcome measures were the patient's desire for a
      prenatal sonogram, the reasons for wanting a sonogram, the number of sonograms
      wanted, and the patient's willingness to pay for the examination. RESULTS: Of the
      150 eligible subjects, 137 (91%) participated and 135 (98%) wanted a prenatal
      sonogram. Fifty-one (37%) of the respondents were willing to pay for the sonogram
      if it was not ordered by their provider. The reasons for wanting a sonogram (to
      determine the sex of the fetus, to ensure that the fetus was healthy, general
      maternal reassurance, and to ensure adequate fetal growth) were similar across
      age, race, and income (military rank). CONCLUSIONS: Our study indicates that most
      women want a sonogram during pregnancy, and many are willing to pay for the
      examination. Women appear to want sonograms for reasons that may not assist their
      provider with immediate clinical decision making. This is a potentially important
      disagreement between cost-saving and patient satisfaction that maternity care
      providers must consider when deciding whether to perform prenatal sonography for
      women with low-risk pregnancies.

PMID- 10923569
TI  - Persistent otitis media with effusion: can it be predicted? A family practice
      follow-up study in children aged 6 months to 6 years.
AB  - BACKGROUND: Otitis media with effusion (OME) has a high rate of spontaneous
      resolution, and a policy of waiting and watching for 3 months is justified. The
      decision about further treatment should be individualized, depending on duration
      and symptoms. Knowledge of the determinants for persistent OME would be helpful
      for identifying patients with a need for active treatment or increased monitoring
      for complications. METHODS: A total of 433 children aged 6 months to 6 years were
      monitored for 3 months in the offices of 57 family physicians. A questionnaire
      pertaining to determinants was completed. The outcome measures were: presence of
      unilateral or bilateral OME or bilateral OME after 3 months. The outcome was
      determined on the basis of tympanometry results. We performed bivariate and
      multivariate analyses. RESULTS: The presence of an upper respiratory tract
      infection (URTI) at the follow-up visit was associated with finding OME at that
      visit. When a URTI was present, no other determinants for persistent OME were
      found. When absent, the determinants for persistent bilateral OME were: no
      history of adenoidectomy, an episode of acute otitis media (AOM) in the first
      year of life, and month of entry into the study (June-November). For persistent
      unilateral or bilateral OME, the only significant determinant was an episode of
      AOM in the first year of life. CONCLUSIONS: Childrenwith 1 or more of the
      following factors need special attention for prevention of the sequelae of
      persistent OME: no history of adenoidectomy, AOM in the first year of life, and
      the presence of bilateral OME in the period between June and November.

PMID- 10923570
TI  - Clinical wisdom and the evidence base. Otitis media with effusion.

PMID- 10923571
TI  - Practical mental health assessment in primary care. Validity and utility of the
      Quick PsychoDiagnostics Panel.
AB  - BACKGROUND: Many case-finding instruments are available to help primary care
      physicians (PCPs) diagnose depression, but they are not widely used. Physicians
      often consider these instruments too time consuming or feel they do not provide
      sufficient diagnostic information. Our study examined the validity and utility of
      the Quick PsychoDiagnostics (QPD) Panel, an automated mental health test designed
      to meet the special needs of PCPs. The test screens for 9 common psychiatric
      disorders and requires no physician time to administer or score. METHODS: We
      evaluated criterion validity relative to the Structured Clinical Interview for
      DSM-IV (SCID), and evaluated convergent validity by correlating QPD Panel scores
      with established mental health measures. Sensitivity to change was examined by
      readministering the test to patients pretreatment and posttreatment. Utility was
      evaluated through physician and patient satisfaction surveys. RESULTS: For major
      depression, sensitivity and specificity were 81% and 96%, respectively. For other
      disorders, sensitivities ranged from 69% to 98%, and specificities ranged from
      90% to 97%. The depression severity score correlated highly with the Beck,
      Hamilton, Zung, and CES-D depression scales, and the anxiety score correlated
      highly with the Spielberger State-Trait Anxiety Inventory and the anxiety
      subscale of the Symptom Checklist 90 (Ps <.001). The test was sensitive to
      change. All PCPs agreed or strongly agreed that the QPD Panel "is convenient and
      easy to use," "can be used immediately by any physician," and "helps provide
      better patient care." Patients also rated the test favorably. CONCLUSIONS: The
      QPD Panel is a valid mental health assessment tool that can diagnose a range of
      common psychiatric disorders and is practical for routine use in primary care.

PMID- 10923572
TI  - The technical performance and clinical feasibility of telecolposcopy.
AB  - BACKGROUND: The purpose of our study was to demonstrate the technical performance
      and clinical feasibility of a telecolposcopic system through assessment of image
      transmission veracity, ease of office system implementation, and the patient's
      acceptance of the electronic image transmission. METHODS: We used a
      telecolposcopic system incorporating a custom software package that integrated
      patient history, current gynecologic status, epidemiologic risk factors, and
      colposcopic images for local medical documentation and transmission. Satisfaction
      questionnaires were developed to measure ease of implementation at the remote
      sites and the patients' acceptance of telecolposcopy. RESULTS: Seventy-nine women
      participated in our trial. From 3 to 20 images were captured for each woman,
      documenting cervical squamous intraepithelial lesions and vaginal and vulvar
      diseases. All images were received without distortions in color, size, or
      orientation. With complete visualization of the squamocolumnar junction there was
      an 86% agreement between the remote and review sites (kappa=.533, P=.019). The
      interobserver agreement for colposcopic impressions was 86% (kappa=.684, P
      <.001), and for colposcopic impressions with histology within one level of
      disease severity, 86% (kappa=.78, P <.001). Colposcopists' and patients'
      satisfaction with telecolposcopy was excellent. More than 95% of the women stated
      that they would rather have their colposcopy locally with electronic transmission
      if an experienced colposcopist were more than 25 miles away. CONCLUSIONS: The
      telecolposcopic system described in our study is technically feasible, can be
      implemented in an office system with limited technical support, and is preferred
      by women who have to travel many miles to receive referral health care.

PMID- 10923574
TI  - Durability of improvement achieved in a clinical trial. Is compliance an issue?
AB  - BACKGROUND: The effects seen in clinical trials may not translate to actual
      practice situations. We examined the persistence of blood pressure effects 31
      months after a clinical trial of treatment with hypotensive agents. METHODS:
      Nineteen previously untreated middle-aged men with hypertension had their office
      and ambulatory blood pressure recorded after 4 weeks of placebo treatment, 4
      weeks of active treatment in a clinical trial, and 31 months of treatment in
      clinical practice. All recording was done by the same physician (IE). RESULTS:
      Mean 24-hour blood pressure was 138/92 mm Hg after 4 weeks of placebo treatment,
      128/85 mm Hg after 4 weeks of active treatment in the clinical trial, and 136/87
      mm Hg after a mean of 31 months of treatment in clinical practice. The
      corresponding blood pressure values > or =140/90 mm Hg during the daytime were
      47%, 24%, and 39%, and office blood pressures were 155/101, 145/93, and 150/91 mm
      Hg. Individual comparison revealed that 6 of the 19 patients had higher mean 24
      hour blood pressure after several months of treatment in clinical practice than
      after 4 weeks of active treatment in the clinical trial. CONCLUSIONS: In our
      study, the significantly reduced blood pressure in the clinical trial did not
      persist when followed up in clinical practice. At follow-up, one third of the
      patients had blood pressure values similar to those before active treatment. The
      reason for this is unclear, but inconsistent compliance may play a part in the
      lack of durability of the improvements. Our results indicate that effects seen in
      short-term clinical trials may not translate to long-term benefits in clinical
      practice.

PMID- 10923573
TI  - The ultrasound-assisted physical examination in the periodic health evaluation of
      the elderly.
AB  - BACKGROUND: Except for specific procedures such as blood pressure measurement,
      the conventional physical examination (PE) does not have sufficient sensitivity
      to be useful as part of the periodic health evaluation. Ultrasound has
      demonstrated greater sensitivity and specificity in numerous studies but has been
      too expensive to be widely employed in health screening. The purpose of our study
      was to determine whether an examination in which conventional and ultrasound
      techniques are blended and applied by a primary care physician might be feasible
      and useful in the periodic health evaluations of senior citizens. METHODS:
      Seventy-two patients presenting to a community-based family physician for
      periodic health evaluations received an ultrasound-assisted physical examination
      (USA-PE) from a second family physician. The results were reported to the primary
      physician, and the outcomes were tracked for periods of up to 2 years. RESULTS:
      Twenty-two of the 72 patients (31%) had abnormalities found by the USA-PE that
      were not apparent during the conventional PE. Five of these patients (7%) had
      serious conditions that received prompt treatment with apparent benefit. Findings
      included endometrial carcinoma, abdominal aortic aneurysm, carotid stenosis,
      hydronephrosis, and urinary retention. CONCLUSIONS: The USA-PE found more
      abnormalities in this group of patients than conventional PE. Whether it can
      improve outcomes for senior citizens undergoing periodic health evaluations in a
      cost-effective manner is yet to be determined.

PMID- 10923575
TI  - Hypothyroidism and diabetes mellitus in an American Indian population.
AB  - BACKGROUND: The clinical relationship between diabetes and hypothyroidism is
      becoming more widely recognized. Although American Indians are disproportionately
      afflicted with diabetes, the occurrence of hypothyroidism within this group has
      not been previously reported. METHODS: We present data from a retrospective chart
      review of health clinic data from a rural isolated northeastern tribe. A total of
      156 cases of diabetes and 25 cases of hypothyroidism were identified among 892
      eligible individuals living in the service area. RESULTS: Both conditions
      exhibited strong sex differences. The prevalences of diabetes (21%) and
      hypothyroidism (5%) among women were higher than those observed among men (13%
      and 0.2%, respectively). The overall prevalence of hypothyroidism among women
      with diabetes (8.8%) varied by age ranging from 5% among women younger than 60
      years to 21% among women aged 60 years and older. CONCLUSIONS: Our findings
      support the need for further investigation of the association between diabetes
      and hypothyroidism in American Indian populations with high prevalence rates of
      diabetes. This association may be of particular interest to family physicians and
      other clinicians caring for American Indian populations.

PMID- 10923576
TI  - Variability in code selection using the 1995 and 1998 HCFA documentation
      guidelines for office services. Health Care Financing Administration.
AB  - BACKGROUND: Documentation guidelines have been developed by the Health Care
      Financing Administration (HCFA) to promote consistent selection of physician
      evaluation and management (E & M) codes. Our goals were to determine whether
      medical providers and auditors agree in their assignment of office codes using
      1995 and 1998 guidelines and to ascertain if the code levels assigned are
      affected by auditor experience and training. METHODS: A total of 1,069
      established patient charts from private family physician offices were reviewed by
      a family practice faculty physician, a family practice resident physician, and a
      professional coder. The main outcome measures were the agreement between the
      auditors and the medical care provider on code selection and the degree to which
      documentation supported the code selected. RESULTS: All auditors agreed with the
      medical provider code selection in only 15.2% (1995 guidelines) and 29.2% (1998
      guidelines) of visits. Professional coders were more likely than faculty
      physicians or resident physicians to agree with the code assigned by the medical
      provider (51.7% vs 40.7% and 39.6%, P <.001). Documentation adequately supported
      the most common office code selection, 99213, in 92.7% (1995) and 91.0% (1998) of
      the charts reviewed. Concurrence among all auditors was only 31.0% (1995) and
      44.3% (1998). CONCLUSIONS: Interobserver differences exist in the assignment of E
      & M codes by auditors using both 1995 and 1998 HCFA guidelines. The 1998
      documentation guidelines produce greater agreement among auditors. The
      documentation supported the level of code billed in the majority of established
      patient office visits.

PMID- 10923578
TI  - Can we reduce the use of echocardiography by using other clinical information to
      identify patients at very low risk for left ventricular systolic dysfunction?

PMID- 10923577
TI  - The placebo response. Recent research and implications for family medicine.
AB  - The placebo response is commonly invoked as a factor in the therapeutic
      relationship between the family physician and the patient, but important recent
      literature can be difficult for family physicians to access. Coordinated
      interdisciplinary research into the placebo response as it occurs in primary care
      settings is lacking. Although there is controversy about the nature and scope of
      the placebo response, important suggestions are emerging about its psychological
      mechanisms (expectancy and conditioning) and the biochemical pathways that act as
      psychosomatic linkages (endorphins, catecholamines and cortisol,
      psychoneuroimmumunology). The available research justifies interventions by
      family physicians that maximize the placebo response in everyday patient
      encounters. These include the sustained partnership approach, working with
      patients on the narratives they construct to explain illness, listening to
      patients, providing them with satisfactory explanations, expressing care and
      concern, and enhancing their sense of control. Notable opportunities exist for
      family medicine investigators to expand the understanding of this phenomenon.

PMID- 10923579
TI  - Does a high-fiber dietary supplement of wheat bran reduce the recurrence rate of
      colorectal adenomas?

PMID- 10923580
TI  - Is gingko biloba more effective than placebo for the treatment of intermittent
      claudication?

PMID- 10923581
TI  - In children with asthma, do inhaled steroids reduce linear growth (height)?

PMID- 10923583
TI  - Waiting for POEMs.

PMID- 10923582
TI  - PSA testing by age.

PMID- 10923584
TI  - Snow in summertime.

PMID- 10923586
TI  - Acquired angioedema associated with sinusitis.
AB  - Acute and chronic sinusitis are major clinical problems faced by physicians in
      several disciplines. Although there is a much studied relationship between
      sinusitis and asthma, as well as a well-known association of sinusitis and
      Wegener's granulomatosis, there is scant evidence suggesting an association of
      angioedema with sinusitis. Angioedema can be extremely disfiguring, and is
      potentially lethal due to compromised airways. It is also a frustrating
      diagnostic dilemma for patients and physicians. A diagnosis is found in fewer
      than 25% of chronic urticaria patients and much less for angioedema. In this
      study, we report the cases of nine patients who were treated for chronic
      sinusitis, but who were referred for episodes of angioedema. Patients with a
      known diagnosis, such as the hereditary form, or drug or food allergies, were
      excluded. Based on clinical suspicion or CT scan results, nine patients were
      treated for chronic sinusitis. Only three had symptoms suggesting a sinus
      infection at presentation. After sinusitis treatment, all nine patients had a
      marked improvement in their angioedema. None had further severe angioedema
      episodes. Some patients continued to have mild episodes of angioedema, which they
      related to recurrence of sinusitis symptoms, and which responded to antibiotics.
      The nine angioedema patients in this series all had strong evidence of sinusitis,
      albeit, most patients had occult disease identified by CT scan. The dramatic
      improvement in angioedema with sinusitis treatment corroborates a causal
      relationship. Such findings encourage the investigation of sinusitis in these
      otherwise idiopathic patients. Sinusitis evaluation may also be indicated for
      urticaria.

PMID- 10923585
TI  - Environmental risk factors (outdoor air pollution and climatic changes) and
      increased trend of respiratory allergy.
AB  - A wealth of evidence suggests that allergic respiratory diseases such as
      rhinosinusitis and bronchial asthma have become more common worldwide in recent
      years and a great deal of etiological and pathogenic research has been carried
      out to evaluate the possible causes of this increasing trend. There is also some
      evidence that increased atmospheric concentrations of pollutants such as ozone
      (O3), nitric oxides (NOx), respirable particulate (PM10) and volatile organic
      chemicals (VOC5), which result from increased use of liquid petroleum gas or
      kerosene, may be linked to the increased prevalence of allergic diseases which
      develop more frequently in urban areas of developed countries. Since bronchial
      asthma is a syndrome which can be aggravated by inhaled compounds, the effects of
      air pollutants on health have been the focus of attention. In fact, various
      studies have demonstrated that inhalation of air pollutants such as O3, nitrogen
      dioxide (NO2) and sulfur dioxide (SO2), either individually or in combination,
      can enhance the airway response to inhaled allergens in atopic subjects, thus
      inducing asthma exacerbations. Moreover, experimental studies have shown that
      diesel exhaust particulate causes respiratory symptoms and is able also to
      modulate the immune response by increasing IgE synthesis in predisposed animals
      and humans. There is also some evidence that air pollutants can interact with
      aeroallergens in the atmosphere and/or on human airways, potentiating their
      effects. In fact, by inducing airway inflammation which increases epithelial
      permeability, some pollutants overcome the mucosal barrier and lead to allergen
      induced responses. However, air pollution and climatic changes should also have
      an indirect effect on allergic response by influencing quantitatively and
      qualitatively the pollen production by allergenic plants.

PMID- 10923587
TI  - Food allergies associated with birch pollen: comparison of Allergodip and
      Pharmacia CAP for detection of specific IgE antibodies to birch pollen related
      foods.
AB  - Sera from 42 patients sensitive to birch pollen were investigated in a pilot
      study with the new Allergodip screening dipstick for cross-reactive allergens
      (Allergopharma). The dipstick contained nine separate allergen pads with extracts
      from birch pollen, hazel pollen, alder pollen, apple, hazelnut, carrot, peach,
      mugwort pollen and celery root (celeriac), together with negative and positive
      controls. The results of the test were assessed visually and classified in
      Allergodip classes 0-4 and compared with the results from the Pharmacia CAP
      method and with the symptoms reported by the patients. The Allergodip method
      showed good reproducibility for color intensity and visual assessment. The
      correspondence between Pharmacia CAP and Allergodip was high for tree pollens (98
      100%) and medium for mugwort pollen, celery, hazelnut and carrot (60-71%). Apple
      and peach showed only 24% and 42% concordance, respectively The sensitivity and
      specificity of Allergodip and Pharmacia CAP differed in regard to food symptoms.
      However, they were always within the range of earlier publications. As a
      consequence of this study, the manufacturer of Allergodip has improved the apple
      allergen extract by adopting a low temperature extraction procedure. Subsequent
      measurements with sera from 14 apple-allergic patients showed greatly improved
      concordance with both CAP measurements and symptoms (93% and 86%, respectively).

PMID- 10923588
TI  - T-cell receptor Vbeta repertoire in mite-allergic subjects after sublingual
      immunotherapy.
AB  - Sublingual immunotherapy has been recognized as an alternative to injected
      immunotherapy for the treatment of allergic diseases. Even if compelling clinical
      evidence supports such a view, few studies are available on its mechanisms of
      action. This study was carried out to investigate the peripheral lymphocyte Vbeta
      repertoire of subjects with mite-allergic respiratory allergy who were either not
      treated or treated for 2 years with mite-specific sublingual immunotherapy. The T
      cell receptor Vbeta distribution was studied by flow-cytometric techniques in
      three subject groups. Group A (untreated) included 19 subjects with symptomatic,
      mite-allergic, low to moderate asthma and/or rhinitis. Group B (treated) was made
      up of 10 asymptomatic subjects treated for 2 years with mite-specific sublingual
      swallow immunotherapy for low to moderate asthma and/or rhinitis. Group C
      (controls) included 10 healthy subjects. The Vbeta usage was investigated with
      monoclonal antibodies specific to the diverse beta segments V3, V5a, V5b, V5c,
      V6a, V8a, V8b and V12a. The comparison between the group A and group C
      repertoires showed a lower expression (p < 0.05) of the beta V8b+ T-cell subset.
      The group B repertoire, when compared with group A, showed a significantly
      greater usage of the beta V5a (p <0.05), 8a (p <0.05) and 12a (p <0.01) segments.
      The significantly lower expression of beta V8b observed in the symptomatic
      untreated group was not present in the group that was asymptomatic after
      treatment. The oligoclonal expansion observed in the treated group was consistent
      with the development of suppressor T-cell and/or of Th1 clones but not with
      deletion mechanisms of induced tolerance.

PMID- 10923589
TI  - Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients.
AB  - Tumor necrosis factor (TNF) is a potent proinflammatory cytokine involved in
      asthma and atopy. Increased TNF-alpha levels have been found in airway biopsies
      and bronchoalveolar lavage fluids from asthmatic patients. Constitutional
      variations in the TNF-alpha secretion levels in vitro are associated with
      molecular polymorphisms located within and around the TNF loci. Our study
      objective was to investigate the association between atopy and two described di
      allelic polymorphisms in the TNF locus: a G to A transition at position -308 in
      the 5'-promoter region of the TNFA gene (TNFA*1 and TNFA*2 alleles) and an Ncol
      restriction fragment length polymorphism (RFLP) in the first intron of the TNFB
      gene (TNFB*1 and TNFB*2 alleles). The genetic study was performed in 65 unrelated
      atopic patients and 60 healthy controls. The regions of interest were amplified
      from genomic DNA using specific primers and polymerase chain reaction. SSP-PCR
      analysis for TNFA -308 polymorphism genotyping and endonuclease digestion
      analysis for the TNFB Ncol RFLP were used. The frequency of the TNFA*2 allele was
      significantly higher in atopic subjects compared to the control group (38.5% vs.
      10.5%; chi2 = 32.06; p <0.0001). The TNFA*2 allele is associated with a higher
      risk for the development of atopy (risk ratio = 9.44; EF = 0.65; chi2 = 30.06 p
      <0.0005). On the other hand, no significant association between the TNFB alleles
      and atopy was found. In conclusion, the TNFA*2 allele could be also a genetic
      risk marker for the predisposition to atopy in our population, as has been
      reported in other studies. Either the TNFA gene itself or a linked gene on
      chromosome region 6p21, which has yet to be identified, is a candidate gene for
      susceptibility to atopy.

PMID- 10923590
TI  - An epidemiological survey on the allergological importance of some emerging
      pollens in Italy.
AB  - Epidemiological studies on the pollens responsible for allergic diseases
      throughout Italy are lacking. Routine diagnostic panels consist prevalently of
      grass, Parietaria, weeds, birch, olive and mugwort. Considering the great variety
      of Italian geographical areas and the observation of the growing allergological
      importance of new botanical species (e.g., ambrosia), a survey on pollen species
      considered "minor" was necessary. A panel of "emerging" pollens (birch, hazelnut,
      alder, hornbeam, cypress, ragweed) and a routine panel were used to skin prick
      test 2,934 consecutive outpatients with respiratory pathology of suspected
      allergic origin, in 21 centers across Italy. A specific questionnaire was
      compiled. It was found that 20.1% of patients did not react to allergens tested,
      28.2% were positive for at least one emerging pollen and 51.7% did not react to
      emerging pollens but tested positive for at least one allergen from the routine
      panel. The prevalence of single pollen species was related to geographical areas.
      Ragweed pollen was shown to provoke asthma much more frequently than other
      pollens. Hitherto scarcely considered pollens play a considerable role in causing
      allergic diseases in Italy. In the great majority of patients, positivity for
      these pollens was associated with positivity to the better recognized group of
      pollen allergens, although in some cases they were the primary pathogenic agent.
      We suggest that these more recently considered allergens be included in routine
      diagnostic panels.

PMID- 10923591
TI  - Low prevalence of allergy to cockroach and latex in asthmatic patients in
      Eskisehir (Anatolia), Turkey.
AB  - Allergy to cockroach and latex are said to be causes of asthma particularly in
      some groups. We studied allergy to cockroach and latex in asthmatic patients from
      Eskisehir (Anatolia), Turkey in order to determine whether these allergens play
      an important role in the Anatolian region. A total of 216 asthmatic patients
      (mean age 43.7+/-11.0 years) were skin tested with common aeroallergens, Blatella
      germanica and latex. Sixty-three patients were allergic (29.1%) and 153 were
      nonallergic (70.8%) according to skin test results. Sensitization to pollens
      (57%) and mites (55.5%) was most common among allergic patients. We found a low
      sensitization to cockroach (4.7%) and latex (1.4%). We suggested that cockroach
      sensitization plays a small role in sensitization in our geographic area and that
      latex sensitization is low in allergic asthmatic patients who were referred for
      reasons other than latex-related symptoms.

PMID- 10923592
TI  - Prevalence of dermographism in children.
AB  - The prevalence of dermographism in our pediatric population was studied in 238
      children of both sexes (128 boys and 110 girls) aged 2-14 years, randomly
      selected from a health care center. Skin reaction was evaluated after 5 min
      pressure (3,200 g/cm2) applied with a dermatographometer on a 5-cm length of
      dorsal skin. The reaction was considered positive when a wheal of more than 2 mm
      was observed. The prevalence of dermographism was found to be 24%, with a
      significant female predominance (33%) over males (16%). Forty-one percent of the
      children with dermographism reported exanthema in response to friction and
      pressure, which was compatible with symptomatic dermographism, compared with only
      5% of those who yielded negative reactions. In order to assess the prevalence of
      dermographism in the atopic population, 100 patients in the 4-14 age range with
      respiratory disease (perennial allergic rhinitis and/or bronchial asthma)
      involving sensitization to aeroallergens (house dust mites and/or Alternaria)
      were studied. A positive response to the application of pressure (3,200 g/cm2)
      was observed in 47% of cases, this figure being significantly higher than in the
      general pediatric population.

PMID- 10923593
TI  - Skin manifestations of a case of phenylbutazone-induced serum sickness-like
      reactions.
AB  - Serum sickness consists of a systemic reaction resulting from the formation of
      soluble circulating immunocomplexes after the introduction of a foreign substance
      into the body We studied a 38-year-old woman diagnosed with anxiety, depression
      and right sacroileitis who was treated with phenylbutazone, ranitidine,
      clomipramine and levomepromazine. After taking this treatment for 1 month, she
      presented with fever, diarrhea, localized edemas, generalized pruritic papular
      and erythematous rash and lymphadenopathies. She presented the same symptoms
      after oral intake of metamizole. The diagnosis was confirmed following a single
      blind, placebo-controlled provocation test with phenylbutazone and a biopsy of
      the affected skin.

PMID- 10923594
TI  - Allergy to Anacardiaceae: description of cashew and pistachio nut allergens.
AB  - Some members of the Anacardiaceae family, such as cashew nut, pistachio nut and
      mango, have been reported to cause immediate allergic reactions. We report three
      cases of anaphylaxis to cashew nuts. With the aim of describing the allergens
      existing in cashew and pistachio nuts, patients were prick tested with cashew and
      pistachio extracts. Specific IgE against both nuts was studied by CAP and SDS
      PAGE/immunoblotting. It was found that skin tests and specific IgE to cashew and
      pistachio nuts were positive in the three patients. Both nuts showed several
      protein bands in SDS-PAGE. The strongest IgE-binding bands had similar molecular
      weights (15, 30 and 60 kDa) in cashew and pistachio nuts. These main bands were
      found to be sensitive to reducing agents. It was concluded that these three
      patients suffered immediate reactions to cashew nut due to an IgE-mediated
      mechanism.

PMID- 10923595
TI  - Localized pustulosis induced by betalactams.
AB  - Localized forms of pustular drug eruptions related to antibiotics are uncommon
      and their mechanism is still unknown. We describe herein a patient who developed
      numerous pin-head pustules without erythema in the peribuccal area after
      ingestion of ceftibuten and amoxicillin. The relationship with these drugs was
      confirmed by single-blind oral challenges. The following tests were performed:
      prick and intradermal tests with benzylpenicilloyl polylysine, minor determinant
      mixture, benzylpenicillin and amoxicillin; patch tests were also carried out with
      benzylpenicillin, amoxicillin, cloxacillin, cefuroxime, ceftriaxone, cefazolin,
      ceftibuten and cefaclor. All cutaneous tests were negative. Controlled single
      blind challenge tests were performed with amoxicillin, cefadroxil, ceftibuten,
      cefuroxime, cefaclor, erythromycin and ciprofloxacin. All betalactam antibiotics
      tested gave a positive reaction, with good tolerance of other antibiotics; this
      would appear to indicate a specific mechanism of hypersensitivity and not an
      unspecific reaction to wide spectrum antibiotics.

PMID- 10923596
TI  - Evaluating outcomes in a population-based asthma program: more work than you
      might think.

PMID- 10923597
TI  - Abnormal steroid responsiveness in atopic dermatitis patients: therapeutic
      implications.

PMID- 10923598
TI  - Antileukotriene agents and aspirin-sensitive asthma: are we removing the second
      bassoonist or skating to where the puck is gonna be?

PMID- 10923599
TI  - T-cell subsets (Th1 versus Th2).
AB  - LEARNING OBJECTIVE: To understand the current status of knowledge in the basic
      field of polarized specific immune responses mediated by CD4+ T helper (Th)
      lymphocytes, based on their profile of cytokine production (type 1 or Th1 and
      type 2 or Th2). DATA SOURCES: Relevant articles and publications from the medical
      literature, especially review articles dealing with properties, mechanisms of
      polarization, transcription regulatory factors, and role in different human
      pathophysiological conditions of Th1 and Th2 cells. CONCLUSIONS: Th1 cells, which
      produce interferon (IFN)-gamma, interleukin (IL)-2 and tumor necrosis factor
      (TNF)-beta, evoke cell-mediated immunity and phagocyte-dependent inflammation.
      Th2 cells, which produce IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13, evoke strong
      antibody responses (including those of the IgE class) and eosinophil
      accumulation, but inhibit several functions of phagocytic cells (phagocyte
      independent inflammation). Both environmental and genetic factors act in concert
      to determine the Th1 or Th2 polarization. Further, Th1-dominated responses are
      involved in the pathogenesis of organ-specific autoimmune disorders, Crohn's
      disease, sarcoidosis, acute kidney allograft rejection, and some unexplained
      recurrent abortions. In contrast, allergen-specific Th2 responses are responsible
      for atopic disorders in genetically susceptible individuals. Further, Th2
      dominated responses play a pathogenic role in both progressive systemic sclerosis
      and cryptogenic fibrosing alveolitis, and favor a more rapid evolution of HIV
      infection towards the full-blown disease. Finally, the Th1/Th2 paradigm can
      provide the basis for the development of new types of vaccines against infectious
      agents and of novel strategies for the therapy of allergic and autoimmune
      disorders.

PMID- 10923600
TI  - Subacute rhinorrhea in a 42-year-old man.

PMID- 10923601
TI  - Outcomes of a population-based asthma management program: quality of life,
      absenteeism, and utilization.
AB  - BACKGROUND: Despite the availability of the National Asthma Education Program
      (NAEP) guidelines since 1991, asthma remains inadequately managed. To improve
      quality of life, functional status, and self-management behavior of asthma
      patients, a large health maintenance organization (HMO) in California implemented
      an asthma management program in 1996. OBJECTIVE: To evaluate the effectiveness of
      an asthma management program in an HMO setting. DESIGN AND SETTING: Prospective
      study. Survey data from members who participated in the intervention program and
      data from members who received usual care were analyzed using propensity score
      technique. RESULTS: A total of 1,043 asthma patients who responded both baseline
      and follow-up survey were included in the analysis. From baseline to followup,
      participants in the in-home intervention program reported significant improvement
      in functional status (improvements range from 0.2 to 7.2), daily use of steroid
      inhaler (+4.1%), daily peak flow meter use (+6.4%), self-reported knowledge of
      what to do for an asthma attack (+12.4%), and feeling that their asthma was under
      control (+10.8%). Absenteeism (-11.8%) and hospitalization due to asthma (-3.5%)
      were significantly reduced from baseline to follow-up. Participants did not
      report significant changes in overuse of beta2-agonists and emergency room visits
      due to asthma. In comparison with the asthmatic patients who received usual care
      (non-participants), participants had significantly greater improvement on daily
      use of steroid inhaler (+4.0% versus -6.0%), daily use of home peak flow meter
      (+6.4% versus 1.9%) and self-reported knowledge on what to do for an asthma
      attack (+12.4% versus +5.4%). CONCLUSION: These findings suggest that population
      based programs can improve functional status, increase self-monitoring and
      knowledge about asthma, and decrease absenteeism and hospitalization for asthma
      by directly providing asthmatic patients with educational materials and self
      monitoring tools. Such "direct-to-consumer" outreach programs may help bridge the
      gap between NAEPs 1991 practice guidelines and the reality of current asthma
      management.

PMID- 10923602
TI  - Adrenocortical function in patients with severe atopic dermatitis.
AB  - BACKGROUND: Adrenocortical suppression is a potential complication of the use of
      topical corticosteroids in patients with atopic dermatitis (AD). OBJECTIVES: To
      determine whether or not the adrenocortical suppression observed in patients with
      severe AD is a sole result of the application of topical steroids. METHODS: A
      total of 45 patients with severe AD that required hospitalization for treatment
      were enrolled. These patients were divided into two groups according to the
      treatment received before hospitalization: group 1 had not used topical
      corticosteroids for at least three months (n = 17), while group 2 had used
      topical corticosteroids daily (n = 28). Otherwise, these two groups were matched
      to clinical characteristics. A rapid ACTH test was performed upon hospital
      admission. Topical corticosteroids were then applied to both groups. The second
      ACTH test was performed just before discharge, an average of 23 days after the
      first test. RESULTS: The basal serum cortisol levels as well as the response to
      ACTH stimulation in the first examination were significantly lower in the AD
      patients than in the controls (P < .001), although there were no significant
      differences in the results between groups 1 and 2. The followup study of
      adrenocortical function at hospital discharge showed that morning basal serum
      cortisol levels were significantly increased in group 1 (P < .01), despite their
      topical corticosteroid treatment, while no significant increase or decrease was
      seen in group 2. CONCLUSION: Our findings suggest that the adrenocortical
      suppression seen in patients with AD may be caused by the percutaneous absorption
      of topical corticosteroids as well as by other factors related to the disease.

PMID- 10923603
TI  - Lack of effect of the 5-lipoxygenase inhibitor zileuton in blocking oral aspirin
      challenges in aspirin-sensitive asthmatics.
AB  - BACKGROUND: Leukotrienes (LTs) have been implicated as major mediators of aspirin
      (ASA)-induced respiratory reactions. It was therefore logical to assume that an
      inhibitor of 5-lipoxygenase (5-LO), such as zileuton, given before and during
      oral challenges with ASA, might prevent ASA-induced respiratory reactions.
      Indeed, in prior studies, pretreatment of ASA-sensitive respiratory disease
      patients with leukotriene modifiers eliminated or attenuated respiratory
      reactions upon re-challenge with the previously established provoking dose of
      ASA. However, doses higher than the provoking doses were not administered during
      these reported studies. OBJECTIVE: We wished to determine whether zileuton
      pretreatment could prevent ASA-induced respiratory reactions in our six
      volunteers with aspirin-sensitive respiratory disease when ASA challenge doses
      were started below the usual provoking dose of 60 mg and then increased until a
      respiratory reaction occurred. METHOD: Aspirin sensitivity was established
      previously in all six patients during a prior ASA oral challenge. In this study,
      pretreatment with zileuton 600 mg qid was initiated 7 days prior to, and
      continued during oral ASA challenges. Patients underwent single-blind oral ASA
      challenges with escalating doses of ASA, every 3 hours, according to our standard
      protocol. RESULTS: All six patients reacted to doses of ASA between 45 and 325
      mg. Four patients experienced bronchospasm (FEV1 declined 19% to 53%) while
      receiving zileuton. All six had naso-ocular reactions. Concentrations of urine
      LTE4 also increased significantly (mean 334 pg/mg Cr at baseline, increasing to
      1024 pg/mg Cr at respiratory reactions). CONCLUSIONS: During ASA challenges,
      zileuton, in standard doses of 600 mg qid was associated with increased synthesis
      of LTs in five of six patients and naso-ocular reactions in all six patients, as
      well as bronchospasm in four patients.

PMID- 10923604
TI  - Ketotifen for asthma in children aged 5 to 15 years: a randomized placebo
      controlled trial.
AB  - BACKGROUND: The prophylactic agent ketotifen has been studied in mild-to-moderate
      asthma. Various trials showed benefit from 10 to 12 weeks of therapy, but no
      trial in children with followup beyond 12 weeks of the drug is available.
      OBJECTIVES: We studied the efficacy of ketotifen, 1 mg twice a day, orally as a
      prophylactic drug in children with asthma. METHODS: The double-blind, placebo
      controlled trial studied 120 asthmatic children of either sex between the ages of
      5 to 15 years at a tertiary care hospital. After an observation period of 4
      weeks, children were randomly assigned to receive either ketotifen, 1 mg twice a
      day, or placebo for 6 months. Antiasthma drugs were continued as required. Main
      outcome measures included average duration for regular antiasthma drugs, average
      symptom scores, symptom free days, peak expiratory flow rate, FEV1, and need for
      emergency room visits. RESULTS: Of the 120 children enrolled, 13 could not
      complete the trial. Thus 58 children remained in the treatment group and 49 were
      in the placebo group. Both groups were comparable in their baseline
      characteristics. The average number of days that required antiasthma drugs were
      significantly less in the treatment group: salbutamol (27+/-4.7 versus 37+/-3.5 P
      < .05), theophylline (37+/-4.7 versus 51+/-4.8 P < .05), oral steroids (2+/-0.4
      versus 5+/-1.6 P < .05), and inhalation steroids (18+/-2.7 versus 16+/-10.8 P <
      .05). The average symptom scores and symptom free days for cough, wheeze, and
      breathlessness also favored the ketotifen group. Emergency room visits were also
      significantly lower in the ketotifen group (20 versus 10 P < .05). Statistically
      significant improvement in all the above parameters were observed after 14 weeks
      of therapy. The mean PEFR, FEV1 and side effects of medications were comparable
      between the two groups. CONCLUSIONS: Ketotifen, 1 mg twice a day, is an effective
      prophylaxis for asthma in children between 5 to 15 years. Significant clinical
      improvement is evident after 14 weeks of therapy.

PMID- 10923605
TI  - Effect of topical nasal azelastine on the symptoms of rhinitis, sleep, and
      daytime somnolence in perennial allergic rhinitis.
AB  - BACKGROUND: Recent data suggested that daytime somnolence in patients with
      allergic rhinitis was secondary to disrupted sleep caused by nasal congestion.
      Medications, which decreased congestion, would be expected to improve sleep and
      daytime somnolence. Previously, we demonstrated that nasal steroids improved all
      three symptoms. The effect of topical nasal antihistamines on these symptoms has
      yet to be studied. OBJECTIVE: The objective of this 8-week, double-blind, placebo
      controlled study was to determine whether topical nasal azelastine was effective
      at decreasing congestion, daytime somnolence, and improving sleep. METHODS: We
      recruited 24 subjects with perennial allergic rhinitis and randomized them in a
      double-blinded, crossover fashion, to receive placebo or azelastine two sprays
      BID, using Balaam's design. Questionnaires, daily diary, and Epworth Sleepiness
      Scale were used as tools. The last 2 weeks of each 4-week treatment period were
      summarized, scored, and compared by PROC MIXED in SAS. RESULTS: The analysis of
      the Rhinitis Severity Score showed significant improvement only of rhinorrhea in
      the azelastine group (P = .03). The symptom severity of nasal congestion and
      daytime somnolence was not significantly different between placebo and
      azelastine. Subjects considered azelastine effective at improving their sleep (P
      = .04), but daytime somnolence (P = .06) and congestion (P = .09) were not
      statistically improved. CONCLUSION: Azelastine is effective in reducing
      rhinorrhea and improving sleep quality. We were unable to demonstrate that
      azelastine can significantly reduce the severity of congestion or daytime
      somnolence.

PMID- 10923606
TI  - Prevalence of asthma, allergic rhinitis, and eczema in 13- to 14-year-old
      children in Kuwait: an ISAAC study. International Study of Asthma and Allergies
      in Childhood.
AB  - OBJECTIVES: To determine the prevalence of asthma and allergic diseases in 13 to
      14 years old children in Kuwait. DESIGN: Supervised self-administered written and
      video questionnaires of the international study of asthma and allergies in
      childhood (ISAAC). SUBJECTS: Students at third and fourth years from 40
      intermediate level schools chosen randomly from across Kuwait. RESULTS: 3,110
      students were surveyed. The prevalence rates (95% CI) in the written
      questionnaire for wheeze ever, current wheeze (within the last 12 months), and
      physician diagnosis of asthma are 25.9% (24.5 to 27.4), 16.1% (15.8 to 17.4), and
      16.8% (15.5 to 18.1) respectively. The prevalence rates (95% CI) for symptoms of
      allergic rhinitis (AR) ever, current symptoms of allergic rhinitis (AR), and
      diagnosis of AR are 43.9% (42.2 to 45.6), 30.7% (29.1 to 32.4) and 17.1% (14.8 to
      18.4) respectively. The prevalence rates (95% CI) for itchy rash ever, current
      itchy rash, and diagnosis of eczema are 17.5% (16.2 to 18.8), 12.6% (11.4 to
      13.8), and 11.3% (10.2 to 12.4) respectively. The prevalence of wheeze ever,
      wheeze during the last year, and physician diagnosis of asthma are higher in
      males compared with females, P < .01. In multiple logistic regression: male
      gender (OR 1.6, 95% CI, 1.3 to 2.0) and diagnosis of AR (OR 1.7, 95% CI, 1.4 to
      2.2) were associated with the physician diagnosis of asthma even after
      controlling for symptoms of asthma. CONCLUSION: This is the first study on the
      prevalence of allergic diseases in Kuwait and it shows that children in Kuwait
      have a moderate prevalence of asthma, AR, and eczema compared with other
      countries where the ISAAC study is done. The prevalence of asthma is higher in
      boys compared with girls.

PMID- 10923607
TI  - Humoral and cellular responses to histamine and pollen allergen in a skin chamber
      model: effect of mizolastine.
AB  - BACKGROUND: Mizolastine is a new non-sedative antihistamine and antiallergic drug
      proven to be effective and safe in the treatment of allergic rhinitis and
      urticaria. OBJECTIVE: To quantitatively explore the time course of mediator
      release and cell recruitment during allergen challenge and the effects of
      mizolastine on the event, using the skin chamber model. METHODS: Twelve pollen
      sensitive patients (23+/-6 years) were included in a double-blind crossover
      study. Patients received 10 mg mizolastine or placebo once daily in the first 4
      day period and, after a 3-week washout period, vice-versa in the crossover
      period. On day 4 of each period, a non-invasive in vivo skin chamber technique
      was used to determine the alteration of vascular permeability, mast cell mediator
      release, the release of soluble intercellular adhesion molecule -1(sICAM-1) in
      skin sites challenged with exogenous histamine or grass pollen allergen extract,
      over an 8-hour period. RESULTS: Challenge with allergen-induced significant mast
      cell activation, as indicated by the release of histamine, tryptase and LTC4, in
      chamber fluids 2 hours after initiation of the allergic reaction and during the
      following 6 hours. Both exogenous histamine and allergen induced significant
      vasodilatation, which was sustained during the 8-hour challenge, as indicated by
      the accumulation of protein in the chamber fluids. Likewise, both histamine and
      allergen induced the release of significant amounts of ICAM-1 throughout the 8
      hour period. Mizolastine significantly inhibited the histamine- and allergen
      induced extravasation (after 2 hours, P = .003; after 8 hours, P = .009; after 2
      hours, P = .044; after 8 hours, P = .003 respectively) and the histamine- and
      allergen-induced--ICAM-1 release (after 2 hours, P = .004; after 8 hours, P =
      .05; after 2 hours, P = .03 respectively). CONCLUSION: Mizolastine strongly
      inhibited the local response to histamine in this skin chamber model with, of
      interest, inhibition of the release of the soluble adhesion-molecule ICAM-1.

PMID- 10923608
TI  - Allergic bronchopulmonary aspergillosis as presenting sign of cystic fibrosis in
      an elderly man.
AB  - BACKGROUND: Although cystic fibrosis is the most common genetic disorder of
      children, its heterogeneous spectrum of severity lends itself to underdiagnosis
      in the older adult patient population where the index of suspicion is not high.
      METHODS: We report a 60-year-old Hispanic man with asthma who presented with
      progressive dyspnea and wheezing unresponsive to inhaled corticosteroid
      treatment. Additionally, he had clinical findings and a past history suggestive
      of cystic fibrosis. Skin testing, radiography and laboratory studies were
      completed to evaluate for allergic bronchopulmonary aspergillosis (ABPA) and
      cystic fibrosis. RESULTS: Test results revealed peripheral eosinophilia and hyper
      IgE. Skin testing to Aspergillus fumigatus (Af) was positive. IgG, IgM, and Af
      specific antibodies were present. High resolution CT scan showed central
      bronchiectasis. Sweat tests were positive on two separate occasions and gene
      analysis showed our patient to have a positive gene mutation at D127ON/D127ON.
      CONCLUSION: Cystic fibrosis should be suspected in the older adult patient with a
      compatible clinical presentation.

PMID- 10923609
TI  - Nitrate anaphylaxis.
AB  - BACKGROUND: Nitrate and nitrite salts are commonly used to preserve and sustain
      color in a number of processed meats. To date there have been no described cases
      of anaphylaxis to either nitrates or nitrites in the literature. OBJECTIVE: We
      report a patient with anaphylaxis to nitrates and nitrites documented by double
      blind, placebo-controlled capsule challenge. METHODS: A 22-year-old previously
      well male, presented to a tertiary referral center with a 4-year history of
      recurrent anaphylaxis after eating take-out food. No further episodes occurred
      while adhering to a strict elimination diet. We performed a double-blind, placebo
      controlled capsule challenge both with food substances and starch placebo. These
      occurred in a hospital setting with full resuscitative procedures available.
      RESULTS: An acute anaphylactic reaction occurred following a challenge to
      nitrates and nitrites. Generalized allergic reactions were observed on separate
      occasions following administration of artificial colorings and metabisulfite.
      There was a mild urticarial reaction following salicylates. He was placed on a
      diet free of sulfites, nitrates, nitrites, and low in salicylates and he has had
      no further reactions. A computer based search of the Medline, Current Contents
      and EMBASE databases found no previously reported cases of urticaria, angioedema,
      or anaphylaxis to either nitrates or nitrites. CONCLUSION: The ingestion of
      processed meats containing nitrate or nitrite salts may be associated with
      angioedema and anaphylaxis and should be considered when investigating patients
      with suspected food allergy.

PMID- 10923610
TI  - Identification of allergenic proteins in condoms by immunoenzymatic methods.
AB  - BACKGROUND: A large increase of allergy to latex proteins has been observed
      lately probably as a result of a great use of latex-containing goods. At present
      these untoward reactions have led to consideration of this problem as a health
      and occupational hazard. It is therefore, necessary to identify the allergens
      contained in latex-manufactured products and to develop effective diagnostic
      tools to detect sensitized individuals. OBJECTIVE: The objective of this study is
      to identify antigenic and allergenic components in latex condoms by using
      chemical, immunochemical, and immunoenzymatic methods. METHODS: The protein
      content of extracts obtained from several brands of condoms was determined and
      characterized by using a modified Lowry method, a quantitative ELISA assay and
      SDS-PAGE. The allergenic behavior of these proteins was studied by IgE
      immunoblotting, EAST and ELISA techniques, using sera from subjects allergic to
      latex products, particularly to latex condoms. RESULTS: Wide variations in the
      protein content (38 to 740 microg/g product) and composition were observed. The
      SDS-PAGE protein profiles showed components ranging from 7 to 94 kD of relative
      molecular weights; most of them were also detected in natural rubber latex. The
      most prominent bands were revealed in the 14 and 30 kD zones. A strong band of 69
      kD in the SDS-PAGE profiles would correspond to a neoantigen, since it was not
      observed in natural latex. The immunoblotting analysis employing sera from 5
      patients allergic to latex condoms showed the presence of 4 components with IgE
      binding capacity (14, 30, 69, and 94 kD). The EAST and ELISA methods showed the
      presence of allergens in all the condom brands studied. CONCLUSIONS: The presence
      of allergenic proteins in several condom brands was demonstrated by different
      immunoenzymatic methods.

PMID- 10923611
TI  - The significance of chicken meat allergy without sensitization to egg proteins.

PMID- 10923612
TI  - Critical energies for SSB and DSB induction in plasmid DNA by low-energy photons:
      action spectra for strand-break induction in plasmid DNA irradiated in vacuum.
AB  - PURPOSE: To measure action spectra for the induction of single-strand breaks
      (SSB) and double-strand breaks (DSB) in plasmid DNA by low-energy photons and
      provide estimates for the energy dependence of strand-break formation important
      for track-structure simulations of DNA damage. MATERIALS AND METHODS: Plasmid
      pMSG-CAT was irradiated as a monolayer, under vacuum, with 7 150eV photons
      produced by a synchrotron source. Yields of SSB and DSB were determined by the
      separation of the three plasmid forms by gel electrophoresis. RESULTS: The yields
      of SSB per incident photon increased from 1.4x 10(-15) SSB per plasmid per
      photon/cm2 at 7eV to 7.5 x 10(-14) SSB per plasmid per photon/cm2 at 150 eV.
      Direct induction of DSB was also detected increasing from 3.4 x 10(-17) DSB per
      plasmid per photon/cm2 at 7eV to 4.1 x 10(-15) DSB per plasmid per photon/cm2 at
      150eV. When the absorption cross-section of the DNA was considered, the quantum
      efficiency for break formation increased over the energy range studied. Over the
      entire energy range, the ratio of SSB to DSB remained constant. CONCLUSIONS:
      These studies provide evidence for the ability of photons as low as 7 eV to
      induce both SSB and DSB. The common action spectrum for both lesions suggests
      that they derive from the same initial photoproducts under conditions where the
      DNA is irradiated in vacuum and a predominantly direct effect is being observed.
      The spectral and dose-effect behaviour indicates that DSB are induced
      predominantly by single-event processes in the energy range covered.

PMID- 10923613
TI  - No dose-dependence of DNA double-strand break misrejoining following alpha
      particle irradiation.
AB  - PURPOSE: To investigate whether an explanation for the high effectiveness of
      densely ionizing radiation with regard to complex biological endpoints can be
      derived from measurements of radiation-induced double-strand break (DSB)
      misrejoining. MATERIALS AND METHODS: Misrejoining of radiation-induced DSB in
      normal human fibroblasts was determined by comparing hybridization analysis of
      large restriction fragments as a measure for correct rejoining, with results from
      a conventional pulsed-field gel electrophoresis technique (FAR) that measures
      total DSB rejoining. In order to investigate DSB misrejoining at doses for which
      chromosome aberration data are available, a dose fractionation protocol was
      applied so that the number of DSB at any given timepoint was low but the
      cumulative amount of misrejoined DSB sufficient for detection and precise
      quantitation. RESULTS AND CONCLUSION: After an acute 80Gy alpha-particle exposure
      and a repair incubation period of 24 h, 50% of all initially induced DSB were
      misrejoined, in agreement with data obtained for X-rays. X-irrradiation with 16 x
      5 Gy, 8 x 10 Gy, 4 x 20 Gy, or 2 x 40 Gy and repair incubation of 24 h following
      each individual dose fraction was recently reported to yield misrejoining
      frequencies that strongly decrease with increasing fractionation (Lobrich et al.
      2000; Genes, Chromosomes and Cancer, 27, 59-68). In the present study, constant
      misrejoining frequencies of 50% were observed after alpha-particle exposure with
      the same fractionation protocol. This difference between alpha-particles and X
      rays is in accordance with the high biological effectiveness of densely ionizing
      radiation and provides a direct link between misrejoining of DSB and
      cytologically visible exchange aberrations. Further evidence suggests that if the
      same dose range is compared, the number of misrejoined DSB exceeds the number of
      microscopically visible aberrations by an order of magnitude for both radiation
      types, probably reflecting the high resolution of the hybridization approach
      compared with cytological techniques.

PMID- 10923614
TI  - Radiation-induced arrest of cells in G2 phase elicits hypersensitivity to DNA
      double-strand break inducers and an altered pattern of DNA cleavage upon re
      irradiation.
AB  - PURPOSE: To determine how radiation-induced arrest in G2 affects the response of
      mammalian cells to a challenging dose of radiation or to antitumour drugs
      producing DNA double-strand breaks. MATERIALS AND METHODS: V79 fibroblast
      survival to 5 Gy gamma-rays followed at intervals by 3 Gy irradiation or by
      contact with an equitoxic dose of neocarzinostatin or etoposide, was measured by
      clonogenic assays. The pattern of radiation-induced DNA double-strand breaks was
      determined by filter elution and CFGE (continuous field gel electrophoresis) or
      PFGE (pulsed-field gel electrophoresis) in G2-arrested cells as well as in nonpre
      irradiated asynchronous or synchronized cells. The cell-cycle phase specificity
      of drug susceptibility was determined in synchronized HeLa cells. RESULTS: Cell
      kill by radiation-drug combined treatment varied markedly with the time elapsed
      after priming irradiation. Pre-irradiated, G2-arrested V79 fibroblasts
      demonstrated excess double-stranded DNA cleavage upon re-irradiation and
      hypersensitivity to drugs and radiation, although maximum resistance to both
      neocarzinostatin and etoposide in synchronized HeLa cells was in G2. This effect
      occurred in the megabase range only, with a peak around 4 Mbp; no change in the
      electrophoretic migration profile of DNA was observed below 1 Mbp. Moreover, the
      DNA migration profile and the yield of DNA cleavage in G2-arrested cells were
      close to those expected from S-phase cells. CONCLUSION: The available data
      suggest that mechanisms operating within the radiation-induced G2 block promote
      susceptibility to DNA double-strand break inducers at this stage. It is also
      proposed that the conformation of DNA in cells accumulated in G2 following
      irradiation bears resemblance to that for cells in S phase, due either to active
      repair mechanisms or to inhibition of chromosome disentanglement at the S-G2
      transition.

PMID- 10923615
TI  - Catalytic inhibition of topoisomerase II in Werner's syndrome cell lines enhances
      chromosomal damage induced by X-rays in the G2 phase of the cell cycle.
AB  - PURPOSE: To investigate whether catalytic topoisomerase II activity by ICRF187, a
      compound that interferes with the catalytic cycle of topoisomerase II without
      causing DNA damage, could result in a modulation of X-ray-induced chromosomal
      damage in Werner's syndrome (WS) cell lines. MATERIALS AND METHODS: Two WS
      (KO375, DJG) and one normal lymphoblastoid cell line (SNW646) were exposed to X
      rays, post-treated with ICRF187 and harvested after various recovery times. Cell
      progression to mitosis was monitored by 5-bromo-2'-deoxyuridine (BrdUrd) and
      fluorescent immmunodetection to analyse chromosomal damage in homogeneous treated
      cell populations in the G1, S or G2 phase of the cell cycle. RESULTS: In WS cell
      lines, catalytic inhibition of topoisomerase II activity by ICRF187 resulted in
      potentiation of X-ray- induced chromosomal damage in the G2 phase of the cell
      cycle. This potentiation was not observed in the G1 or S phases of the cell
      cycle, neither in WS nor normal cells. CONCLUSION: These results point out the
      possibility that Werner's syndrome protein (WRNp) might play a role in a G2
      recombinational pathway of double-strand break repair, cooperating with
      topoisomerase II and thus contributing to maintain genomic integrity.

PMID- 10923616
TI  - Analysis of chromosome aberrations in nuclear-power-plant workers considering the
      lifetime of lymphocytes.
AB  - PURPOSE: To analyse chromosome aberrations in nuclear-power-plant workers taking
      account of the mean lifetime of lymphocytes (MLTL). MATERIALS AND METHODS:
      Analysis of chromosome aberrations was performed on peripheral lymphocytes from
      395 nuclear-power-plant workers and 135 controls. An equivalent acute dose (EAD)
      was calculated utilizing MLTL values of either 4.3 or 10 years. RESULTS: Using an
      MLTL value of 10 years produced an EAD range of 0.O1 mSv -182mSv(mean 46.6mSv),
      while using an MLTL, of 4.3 years produced results ranging from 0.01 mSv to 86.2
      mSv (mean 23.4 mSv). A significant increase of chromosome-type exchange by the
      equivalent acute dose was observed using an MLTL of either 10 or 4.3 years when
      including the control in the analysis, but a significant increase was not seen
      when only the exposed was considered. A significant increase of chromosome-type
      deletion by EAD was seen even when only the exposed group was considered.
      CONCLUSIONS: EAD values based on an MLTL of either 4.3 or 10 years, as well as
      cumulative dose, showed no significant association with chromosome aberrations,
      when radiation workers only were analysed. The narrow dose range examined in this
      study might have contributed to this finding.

PMID- 10923617
TI  - High-LET radiation-induced aberrations in prematurely condensed G2 chromosomes of
      human fibroblasts.
AB  - PURPOSE: To determine the number of initial chromatid breaks induced by low- or
      high-LET irradiations, and to compare the kinetics of chromatid break rejoining
      for radiations of different quality. MATERIAL AND METHODS: Exponentially growing
      human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon
      (290MeV/u), silicon (490MeV/u) and iron (200 and 600 MeV/u). Chromosomes were
      prematurely condensed using calyculin A. Chromatid breaks and exchanges in G2
      cells were scored. PCC were collected after several post-irradiation incubation
      times, ranging from 5 to 600 min. RESULTS: The kinetics of chromatid break
      rejoining following low- or high-LET irradiation consisted of two exponential
      components representing a rapid and a slow time constant. Chromatid breaks
      decreased rapidly during the first 10min after exposure, then continued to
      decrease at a slower rate. The rejoining kinetics were similar for exposure to
      each type of radiation. Chromatid exchanges were also formed quickly. Compared to
      low-LET radiation, isochromatid breaks were produced more frequently and the
      proportion of unrejoined breaks was higher for high-LET radiation. CONCLUSIONS:
      Compared with gamma-rays, isochromatid breaks were observed more frequently in
      high-LET irradiated samples, suggesting that an increase in isochromatid breaks
      is a signature of high-LET radiation exposure.

PMID- 10923618
TI  - Derivation of low-dose extrapolation factors from analysis of curvature in the
      cancer incidence dose response in Japanese atomic bomb survivors.
AB  - PURPOSES: To assess the degree of overestimation in low-dose cancer risk when
      models linear in dose are fitted to cancer data. MATERIALS AND METHODS:
      Examination of the quadratic and the linear coefficients (in dose) in the
      Japanese atomic bomb survivor cancer incidence data, based on follow-up to 1987
      and taking separate account of random errors in DS86 neutron and DS86 gamma dose
      estimates and systematic errors in Hiroshima DS86 neutron dose estimates.
      RESULTS: When the 0-4Gy dose range is used, the low-dose extrapolation factor for
      all solid tumours, assessing the degree to which low-dose cancer risks are
      overestimated by fitting a model linear in dose, is 1.06 (95% CI 0.78, 1.62) and
      so is not significantly different from 1; the associated ratio of the quadratic
      to the linear coefficients is 0.06 Sv(-1) (95% CI -0.22, 0.67). The best estimate
      of the low-dose extrapolation factor for leukaemia is 2.47 (95% CI 1.24, >
      1,000). The ratio of the quadratic to the linear coefficients is 1.81 Sv(-1) (95%
      CI 0.21, > 1,000). When various types and groupings of solid tumours are
      considered there is not generally any strong evidence for upward curvature; for
      only two out of the six solid tumour groupings are there indications of
      appreciable upward curvature in the dose response, and in no instance is this
      statistically significant. Consideration of a lower dose range (0-2Gy rather than
      0-4 Gy) results in the low-dose extrapolation factor for solid tumours increasing
      to 1.21 (95% CI 0.81, 2.45), with corresponding increases for solid tumour
      subtypes; the corresponding quantity for leukaemia decreases to 1.73 (95% CI
      0.79, 147.67). Three out of the six solid tumour subtypes now show appreciable
      upward curvature. If there is additional adjustment of the Hiroshima neutron dose
      estimates over the 0-2 Gy dose range, the low-dose extrapolation factor for all
      solid tumours increases still further, to 1.43 (95% CI 0.97, 2.72), whereas for
      leukaemia this quantity is further reduced, to 1.58 (95% CI 0.90, 10.58).
      CONCLUSIONS: There is marked upward curvature in the dose response for leukaemia.
      For solid tumours there is little indication of upward curvature in the dose
      response over the 0-4 Gy dose range, although over the 0-2 Gy dose range and
      after adjustment of Hiroshima DS86 neutron dose estimates the upward curvature is
      more pronounced. Uncertainties in the likely adjustments to the Hiroshima DS86
      neutron dose estimates imply that these findings should be treated with caution.

PMID- 10923619
TI  - Chromosomal aberrations and hprt mutant frequencies in long-term American
      thorotrast survivors.
AB  - PURPOSE: Patients injected with thorotrast, a radiologic contrast medium used
      from the 1920s to early 1950s, received chronic internal exposure to thorium-232,
      an alpha-emitter. Epidemiologic studies have observed markedly elevated risks of
      death from hepatic and hematologic cancers and extensive chromosomal damage among
      these patients. Few investigations have correlated multiple measures of genetic
      damage to determine whether these have independent induction kinetics. The
      distribution of chromosomal aberrations (CA) and mutant frequencies (MF) at the
      hypoxanthine phosphoribosyltransferase (hprt) locus was evaluated in eight long
      term thorotrast survivors (mean exposure time=47.4 years) and five individuals
      who received a nonradioactive contrast medium during the same era. MATERIALS AND
      METHODS: Peripheral blood lymphocytes were harvested from whole blood, CA were
      scored in 500 complete metaphases and a clonal assay was used to determine hprt
      MF. Symmetrical aberrations were not evaluated. Differences in frequencies and
      correlations between endpoints were assessed using nonparametric methods.
      RESULTS: Thorotrast-exposed individuals differed from the comparison group in
      total number of multicentrics and centric and acentric rings (per 500 cells
      [median, mean +/- sd]: 11, 18.3+/-23.1 vs 2, 2.4+/-1.1, p =0.04). There was no
      difference between the groups on hprt MF (12.6, 15.9+/-13.5 vs 16.6, 14.0+/-8.8[
      x 10(-6)]; p= 1.0). Among the exposed, hprt MF was moderately correlated with the
      frequency of asymmetrical chromosomal aberrations, although the association was
      not statistically significant. CONCLUSION: Noting the limitations of small
      samples, long-term thorotrast survivors were observed to be at an increased risk
      for genetic damage.

PMID- 10923620
TI  - Absence of delayed chromosomal instability in a normal human fibroblast cell line
      after 125I iododeoxyuridine.
AB  - PURPOSE: To seek the delayed appearance of chromosomal abnormalities in human
      fibroblasts exposed to the Auger electron emitter 125I. MATERIALS AND METHODS:
      Normal untransformed human fibroblasts, HF19, were exposed to a concentration of
      [I125]IUdR, which allowed the survival of 37% of clonogens. Chromosomal analysis
      using both conventional Giemsa and fluorescence in situ hybridization (FISH) was
      undertaken on non-clonal bulk cultures from 2 to 39 days after treatment.
      RESULTS: The data show a declining level of unstable aberrations in the progeny
      of HF19 fibroblasts exposed to [I125]IUdR, eventually reaching control levels.
      CONCLUSIONS: The results provide evidence that [125I]IUdR does not induce ongoing
      chromosomal instability in long-term culture, and gives further support to the
      use of Auger-electron emitting radionuclides in the treatment and diagnosis of
      tumours.

PMID- 10923621
TI  - Absence of genomic instability in mice following prenatal low dose-rate gamma
      irradiation.
AB  - PURPOSE: To determine whether mice exposed to an extended low dose of gamma
      irradiation during most of their prenatal period express increased frequencies of
      micronucleated polychromatic erythrocytes (fMPCE) and/or micronucleated
      normochromatic erythrocytes (fMNCE) several weeks after the end of irradiation.
      METHODS: Female CBA/Ca mice were gamma-irradiated for an average of 16 days
      during their pregnancy. The mice were exposed to dose rates of 0, 44, 99 and 265
      mGy/day. At 1-2 days prior to parturition the mice were removed from exposure.
      Then, 36 days after birth, peripheral blood was drawn from all offspring (74
      mice). Using flow-cytometer-based analysis, the frequencies of MPCE and MNCE were
      determined. From each animal about 170,000 PCE were analysed. RESULTS: No delayed
      effects in terms of higher fMPCE or fMNCE were observed among the in utero
      exposed mice of either gender. On the contrary, a significant (p<0.001) reduction
      of fMPCE was found among the male offspring exposed at the highest dose rate.
      CONCLUSION: Gamma-irradiation of mice during their prenatal stage did not induce
      damage in erythroid stem cells that can be detected as persistent or delayed
      chromosome aberrations (i.e. micronucleated erythrocytes) at 35 days after the
      end of exposure.

PMID- 10923622
TI  - Time-course of the hazard of murine nephropathy induced by total-body
      irradiation.
AB  - PURPOSE: We investigated the form of the hazard function for total-body
      irradiation (TBI) induced nephropathy in mice during 1.5 years of follow-up.
      MATERIAL AND METHODS: The material was collected from our previously published
      data. Following single-dose or fractionated irradiation and bone marrow
      transplantation (BMT) the mice were tested regularly for kidney damage using the
      CrEDTA residual activity, percentage haematocrit and blood urea nitrogen
      endpoints. The hazard rate was studied in the pooled data of 172 mice for all
      three endpoints, while fractionation sensitivity was estimated from the direct
      analysis, which was performed using the CrEDTA residual activity endpoint and the
      actual follow-up data in individual mice. RESULTS: The hazard rate of kidney
      damage following TBI and BMT showed a biphasic pattern that is most evident with
      the CrEDTA residual activity endpoint, with a reduced risk of renal failure
      around week 36 after TBI. Assessment of kidney function in individual animals
      showed evidence of recovery from radiation damage around week 36 after TBI. An
      analysis of fractionation sensitivity showed that the first wave was
      characterized by an alpha/beta ratio of 8.4Gy (95% CI: 4.0-14.3Gy), while the
      alpha/beta ratio for the second wave was estimated at 6.1 Gy (95% CI: 3.3 9.8
      Gy). CONCLUSIONS: The biphasic nature of the hazard function reported here may be
      a unique feature of TBI-induced renal damage. Differentiation between the two
      phases in terms of their alpha/beta ratio was not possible. The biological basis
      of this observation remains to be clarified. The reported high alpha/beta ratio
      of kidney damage in the TBI situation may have important clinical implications.

PMID- 10923623
TI  - The general relation between tissue response to x-radiation (alpha/beta-values)
      and the relative biological effectiveness (RBE) of protons: prediction by the
      Katz track-structure model.
AB  - PURPOSE: Experimental data suggest that the relative biological effectiveness
      (RBE) of protons compared to x-rays may be determined by the alpha/beta-ratio of
      the x-ray survival curve. The data are referring to the centre of a spread-out
      Bragg peak (SOBP) formed to deliver a homogeneous dose to the tumour by
      modulating the proton energy. In an effort to explore the basis for this
      observation, calculations were performed to investigate the response of different
      biological targets through a range of proton energies and doses. MATERIALS AND
      METHODS: To describe the x-ray survival curve, the parameters of the linear
      quadratic equation, alpha and beta, as well as those of the multi-target/single
      hit equation, n and D0, were considered. These parameters were varied to
      investigate the RBE using the Katz track-structure model. Known cell line
      characterizations, as well as different hypothetical cells assuming different
      alpha/beta-ratios but similar target size parameters in the framework of the
      track-structure theory, were considered. RESULTS: The RBE was found to increase
      with increasing alpha/beta when the parameter n was varied, but to decrease with
      increasing alpha/beta when D0 was varied. This held when all other
      radiosensitivity parameters were assumed to stay constant. Thus, the RBE cannot
      be predicted by the alpha/beta-ratio alone. CONCLUSIONS: Although there is no
      direct correlation between the proton RBE and the parameters describing the x-ray
      survival curve, the track-structure model predicts a tendency for late-responding
      tissues (low alpha/beta) to have higher RBE values than early-responding tissues
      (high alpha/beta). These calculations reinforce the experimental findings, but
      also strongly suggest that there are circumstances in which the tendency for RBE
      to increase with increasing alpha/beta does not occur, or even could be reversed.

PMID- 10923624
TI  - In vitro response of human and porcine vascular cells exposed to high dose-rate
      gamma-irradiation.
AB  - AIM: The objective of this study was to compare the in vitro response of human
      and pig endothelial cells, smooth muscle cells and fibroblasts exposed to
      conventional high dose-rate gamma-irradiation. MATERIALS AND METHODS: Clonogenic
      cell survival and growth responses were obtained after irradiation of plateau
      phase cells with a 60Co source at a dose-rate of 1.5 Gy/min. DNA single-strand
      breaks were also evaluated using an alkaline filter elution technique. RESULTS:
      Overall, both the pig and human cell lines showed a similar response to
      conventional high dose-rate irradiation. Using clonogenic assays, the human
      aortic smooth muscle cell line was more sensitive than the fibroblast and
      endothelial cell lines, whereas the pig endothelial cell line was more sensitive
      than smooth muscle cells and fibroblasts. Shortly after irradiation (10 days)
      there was a temporary growth arrest, which was similar for endothelial, smooth
      muscle cells and fibroblasts with doses above 6 Gy. There was also a non-linear,
      dose-dependent growth delay up to 4 weeks after irradiation. This effect was also
      consistent between the different cell lines. Using alkaline filter elution, there
      was no significant difference in relative elution between endothelial cells,
      smooth muscle cells and fibroblasts, indicating similar DNA damage among the
      different cell lines. CONCLUSION: The in vitro response of human and pig
      endothelial cells, smooth muscle cells and fibroblasts exposed to high dose-rate
      irradiation appeared similar. The pig model seems well suited to evaluate the
      short- and long-term effects of ionizing radiation in the prevention of
      restenosis after vessel injury.

PMID- 10923625
TI  - Metallothionein induction in human CNS in vitro: neuroprotection from ionizing
      radiation.
AB  - PURPOSE: There have been extensive studies on the regulation of metallothionein
      (MT) synthesis, and its biological role in liver and kidney. Although there are
      few reports on brain MT, there is a growing interest in the role of MT in brain.
      There have been no publications to date on MT synthesis in the human central
      nervous system (CNS) following exposure to ionizing radiation. In the present
      study, primary human CNS cultures were used to examine the effect of ionizing
      radiation on MT mRNA and protein synthesis. In the same cultures, the
      neuroprotective effects of zinc (Zn) and cadmium (Cd)-induced MT synthesis from
      high-dose radiation were also examined. MATERIALS AND METHODS: Primary, serum
      free, human CNS cultures were exposed to 30 or 60 Gy gamma-rays. The total MT
      protein was then measured by a Cd-heme assay, and mRNA for MT-II and MT-III was
      detected by reverse transcription polymerase chain reaction (RT-PCR).
      Cytotoxicity was measured by LDH release and apoptotic cell death by DNA
      fragmentation analysis. Sublethal neuroglial injury was assessed morphologically
      using specific astrocytic (glial fibrillary acidic protein--GFAP) and neuronal
      (microtubule-associated protein 2--MAP2) immunohistochemical markers. RESULTS:
      The total MT protein content was increased 12h after exposure to 30Gy. The
      increase in MT content in response to 60Gy was not statistically significant. MT
      II mRNA levels increased at 3 and 6h after exposure to 30Gy gamma-rays, with a
      maximum expression at 12-24 h. MT-III mRNA was not significantly affected.
      Exposure to 60 Gy, but not 30 Gy, caused a marked increase in LDH release. Cells
      exposed to 30 Gy or less showed some apoptotic cell death by DNA fragmentation
      analysis, while exposure to 60 Gy resulted in a DNA smear confirmed by LDH
      assays. Preinduction of MT by 5 microM Cd or 100 microM Zn resulted in a
      significant reduction in radiation-induced LDH release. Morphological evaluations
      revealed that Cd or Zn preincubation led to relative preservation of MAP2
      staining and GFAP. CONCLUSION: Both MT protein and MT-II mRNA can be induced in
      human CNS cells by ionizing radiation. Furthermore, induction of MT synthesis
      with Zn and Cd can protect human CNS cells from radiation-induced cytocidal and
      sublethal injuries. Both findings have implications in the development of
      strategies to protect human CNS tissue from damage during radiotherapy.

PMID- 10923626
TI  - Dissociation of AMP-activated protein kinase activation and glucose transport in
      contracting slow-twitch muscle.
AB  - 5'AMP-activated protein kinase (AMPK) has been suggested to be a key regulatory
      protein in exercise signaling of muscle glucose transport. To test this
      hypothesis, we investigated whether muscle glycogen levels affect AMPK activation
      and glucose transport stimulation similarly during contractions. Rats were
      preconditioned by a combination of swimming exercise and diet to obtain a
      glycogen-supercompensated group (high muscle glycogen content [HG]) with
      approximately 3-fold higher muscle glycogen levels than a glycogen-depleted group
      (low muscle glycogen content [LG]). In perfused fast-twitch muscles, contractions
      induced significant increases in AMPK activity and glucose transport and
      decreases in acetyl-CoA carboxylase (ACC) activity in both HG and LG groups.
      Contraction-induced glucose transport was nearly 2-fold (P < 0.05) and AMPK
      activation was 3-fold (P < 0.05) higher in the LG group compared with the HG
      group, whereas ACC deactivation was not different between groups. Thus, there was
      a significant positive correlation between AMPK activity and glucose transport in
      contracting fast-twitch muscles (r = 0.80, P < 0.01). However, in slow-twitch
      muscles with HG, glucose transport was increased 6-fold (P < 0.05) during
      contractions, whereas AMPK activity did not increase. In contracting slow-twitch
      muscles with LG, the increase in AMPK activity (315%) and the decrease in ACC
      activity (54 vs. 34% at 0.2 mmol/l citrate, LG vs. HG) was higher (P < 0.05)
      compared with HG muscles, whereas the increase in glucose transport was identical
      in HG and LG. In conclusion, in slow-twitch muscles, high glycogen levels inhibit
      contraction-induced AMPK activation without affecting glucose transport. This
      observation suggests that AMPK activation is not an essential signaling step in
      glucose transport stimulation in skeletal muscle.

PMID- 10923627
TI  - Pancreastatin modulates insulin signaling in rat adipocytes: mechanisms of cross
      talk.
AB  - Pancreastatin (PST), a chromogranin A-derived peptide, has counterregulatory
      effects on insulin in the hepatocyte and the adipocyte, suggesting a possible
      role in insulin resistance. The mechanism of PST action on glucose and lipid
      metabolism is typical of a calcium-mobilizing hormone and involves a receptor
      Gq/11 protein-phospholipase C (PLC)-beta pathway. In the rat adipocyte, PST
      inhibits insulin-mediated glucose transport, glucose utilization, and lipid
      synthesis, and it has a lipolytic effect but stimulates basal and insulin
      stimulated protein synthesis. We have also recently studied the PST receptor
      effector system in adipocyte membranes. To further investigate the mechanisms of
      PST effect on insulin action, we studied the cross-talk of PST with insulin
      signaling in the rat adipocyte. We found that PST inhibits insulin-stimulated
      GLUT4 translocation to the membrane, which may explain the reported inhibition of
      glucose transport. Tyrosine phosphorylation of the activated insulin receptor,
      insulin receptor substrate (IRS)-1, and p60-70 was also blunted, preventing their
      association with p85 phosphatidylinositol 3-kinase (PI3K) and their activity. The
      mechanism of this inhibition involves the activation of the "classical" protein
      kinase C isoforms and the serine phosphorylation of insulin receptor and IRS-1.
      On the other hand, PST activates the mitogen-activated protein kinase (MAPK)
      signaling module and enhances the effect of insulin. This pathway may account for
      the described effect of PST on protein synthesis. In conclusion, PST seems to
      inhibit the insulin-stimulated PI3K pathway in the adipocyte, whereas it
      activates the MAPK pathway. These data provide some clues to the PST cross-talk
      with insulin signaling that may explain the PST effects on glucose metabolism and
      protein synthesis.

PMID- 10923628
TI  - Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle.
AB  - Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle
      during exercise are related to the phosphorylation and inhibition of acetyl-CoA
      carboxylase (ACC), and secondary to this, a decrease in the concentration of
      malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in
      the concentration of malonyl-CoA during exercise; however, measurements of ACC
      activity have not been reported. Thus, whether the same mechanism operates in
      human muscle in response to physical activity remains uncertain. To investigate
      this question, ACC was immunoprecipitated from muscle of human volunteers and its
      activity assayed in the same individual at rest and after one-legged knee
      extensor exercise at 60, 85, and 100% of knee extensor VO2max. ACC activity was
      diminished by 50-75% during exercise with the magnitude of the decrease generally
      paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with
      protein phosphatase 2A restored activity to resting values, suggesting the
      decrease in activity was due to phosphorylation. The measurement of malonyl-CoA
      in the muscles revealed that its concentration is 1/10 of that in rats, and that
      it is diminished (12-17%) during the higher-intensity exercises. The respiratory
      exchange ratio increased with increasing exercise intensity from 0.84 +/- 0.02 at
      60% to 0.99 0.04 at 100% VO2max. Calculated rates of whole-body fatty acid
      oxidation were 121 mg/min at rest and 258 +/- 35, 264 +/- 63, and 174 +/- 76
      mg/min at 60, 85, and 100% VO2max, respectively. The results show that ACC
      activity, and to a lesser extent malonyl-CoA concentration, in human skeletal
      muscle decrease during exercise. Although these changes may contribute to the
      increases in fat oxidation from rest to exercise, they do not appear to explain
      the shift from mixed fuel to predominantly carbohydrate utilization when exercise
      intensity is increased.

PMID- 10923630
TI  - T-cell responses to enterovirus antigens in children with type 1 diabetes.
AB  - Enterovirus infections, implicated in the pathogenesis of type 1 diabetes in a
      number of studies, may precipitate the symptoms of clinical diabetes and play a
      role in the initiation of the beta-cell damaging process. The aim of this study
      was to evaluate whether cellular immune responses to enterovirus antigens are
      abnormal in children with type 1 diabetes. Lymphocyte proliferation responses to
      enterovirus antigens were analyzed in 41 children with new-onset type 1 diabetes,
      23 children with type 1 diabetes for 4-72 months, and healthy control children in
      subgroups matched for HLA-DQB1 risk alleles, sex, and age. Children with diabetes
      for 4-72 months more often had T-cell responses to the Coxsackievirus B4-infected
      cell lysate antigen than children with new-onset diabetes (P < 0.01) or control
      children (P < 0.01). Responses to recombinant nonstructural protein 2C of
      Coxsackievirus B4 were also more frequent in children with type 1 diabetes for 4
      72 months when compared with control subjects (P = 0.03), whereas the responses
      to purified Coxsackievirus B4 and recombinant VP0 protein, which did not contain
      nonstructural proteins, did not differ. These data suggest that T-cell responses
      to Coxsackievirus B4 proteins and particularly to the antigens containing the
      nonstructural proteins of the virus are increased in children with type 1
      diabetes after the onset of the disease. However, in children with new-onset
      diabetes, responses were normal or even decreased. This phenomenon was specific
      for enteroviruses and could be caused by trapping of enterovirus-specific T-cells
      in the pancreas.

PMID- 10923629
TI  - 1alpha,25-dihydroxyvitamin D3 induces an autoantigen-specific T-helper 1/T-helper
      2 immune shift in NOD mice immunized with GAD65 (p524-543).
AB  - Prevention of type 1 diabetes in NOD mice by 1,25-dihydroxyvitamin D3
      [1alpha,25(OH)2D3] is accompanied by a T-helper (Th) 1/Th2 cytokine shift in the
      pancreas. The aim of this study was to investigate whether this immune shift also
      occurs outside of the pancreas and whether it is limited to autoantigen-specific
      immune responses. NOD mice treated with 1alpha,25(OH)2D3 (5 microg/kg every 2
      days) or control vehicle were immunized with GAD65 (p524-543) or ovalbumin (OVA)
      in the rear footpads. First, we examined T-cell proliferation and cytokine
      production (via enzyme-linked immunosorbent assay) of draining lymph node cells
      in vitro with or without peptide rechallenge. Although no differences in
      proliferation were measured between control and 1alpha,25(OH)2D3-treated mice
      after in vitro GAD65 rechallenge, a marked shift in cytokine secretion profile
      was seen in 1alpha,25(OH)2D3-treated mice: interleukin-4 was increased (37 +/- 5
      vs. 21 +/- 12 pg/ml in controls, P < 0.005), whereas gamma-interferon levels were
      decreased (6 +/- 3 vs. 9 +/- 3 ng/ml in controls, P < 0.05). This shift was
      absent in OVA-primed mice. Second, we measured cytokine profiles by reverse
      transcriptase-polymerase chain reaction in popliteal lymph nodes at different
      time points after priming with GAD65 or OVA in vivo. A marked Th1/Th2 shift
      occurred in 1alpha,25(OH)2D3-treated mice after in vivo priming with GAD65.
      Again, this shift was absent after OVA immunization. Finally, we measured
      cytokine profiles after rechallenge with a panel of autoantigens (GAD65, heat
      shock protein 65, insulin B-chain) and control antigens (OVA, keyhole limpet
      hemocyanine, myelin proteolipid protein, tetanus toxin) and confirmed the Th1/Th2
      shift in autoantigen-injected mice but not in control antigen-injected mice. In
      conclusion, the immune deviation induced by 1alpha,25(OH)2D3 in NOD mice can also
      be induced in the peripheral immune system but is limited to pancreatic
      autoantigens.

PMID- 10923631
TI  - Enterovirus infection as a risk factor for beta-cell autoimmunity in a
      prospectively observed birth cohort: the Finnish Diabetes Prediction and
      Prevention Study.
AB  - Previous studies suggest that enterovirus infections may initiate and accelerate
      beta-cell damage years before the clinical manifestation of type 1 diabetes. We
      have now analyzed the role of enterovirus infections in the initiation of
      autoimmunity in children who have tested positive for diabetes-associated
      autoantibodies in a prospective study starting at birth (the Finnish Diabetes
      Prediction and Prevention Study). The frequency of enterovirus infections was
      studied using both serology and testing for the presence of enterovirus RNA in
      the sera of 21 children who developed and retained autoantibodies and in 104
      control subjects chosen from the same study cohort and matched for the time of
      birth, sex, and HLA alleles determining genetic diabetes susceptibility. Sample
      intervals were taken as basic units of follow-up, to which the observed number of
      infections was adjusted. Enterovirus infections were detected in 26% of sample
      intervals in the case subjects and in 18% of the sample intervals in the control
      children (P = 0.03). A temporal relationship between enterovirus infections and
      the induction of autoimmunity was found; enterovirus infections were detected in
      57% of the case subjects during a 6-month follow-up period preceding the first
      appearance of autoantibodies compared with 31% of the matched control children in
      the same age-group (odds ratio 3.7, 95% CI 1.2-11.4). The frequency of adenovirus
      infections did not differ between the patient and control groups. Our data imply
      that enterovirus infections are associated with the development of beta-cell
      autoimmunity and provide evidence for the role of enteroviruses in the initiation
      of beta-cell destruction.

PMID- 10923633
TI  - Beta-cell proliferation and apoptosis in the developing normal human pancreas and
      in hyperinsulinism of infancy.
AB  - Hyperinsulinism of infancy (HI), also known as persistent hyperinsulinemic
      hypoglycemia of infancy, is a rare genetic disorder that occurs in approximately
      1 of 50,000 live births. Histologically, pancreases from HI patients can be
      divided into 2 major groups. In the first, diffuse HI, beta-cell distribution is
      similar to that seen in normal neonatal pancreas, whereas in the second, focal
      HI, there is a discrete region of beta-cell adenomatous hyperplasia. In most
      patients, the clinical course of the disease suggests a slow progressive loss of
      beta-cell function. Using double immunostaining, we examined the proportion of
      beta-cells undergoing proliferation and apoptosis during the development of the
      normal human pancreas and in pancreases from diffuse and focal HI patients. In
      the control samples, our findings show a progressive decrease in beta-cell
      proliferation from 3.2 +/- 0.5% between 17 and 32 weeks of gestation to 0.13 +/-
      0.08% after 6 months of age. In contrast, frequency of apoptosis is low (0.6 +/-
      0.2%) in weeks 17-32 of gestation, elevated (1.3 +/- 0.3% ) during the perinatal
      period, and again low (0.08 +/- 0.3%) after 6 months of age. HI beta-cells showed
      an increased frequency of proliferation, with focal lesions showing particularly
      high levels. Similarly, the proportion of apoptotic cells was increased in HI,
      although this reached statistical significance only after 3 months of age. In
      conclusion, we demonstrated that islet remodeling normally seen in the neonatal
      period may be primarily due to a wave of beta-cell apoptosis that occurs at that
      time. In HI, our findings of persistently increased beta-cell proliferation and
      apoptosis provide a possible mechanism to explain the histologic picture seen in
      diffuse disease. The slow progressive decrease in insulin secretion seen
      clinically in these patients suggests that the net effect of these phenomena may
      be loss of beta-cell mass.

PMID- 10923632
TI  - Association between rotavirus infection and pancreatic islet autoimmunity in
      children at risk of developing type 1 diabetes.
AB  - Pancreatic islet autoimmunity leading to type 1 diabetes could be triggered by
      viruses in genetically susceptible individuals. Rotavirus (RV), the most common
      cause of childhood gastroenteritis, contains peptide sequences highly similar to
      T-cell epitopes in the islet autoantigens GAD and tyrosine phosphatase IA-2 (IA
      2), suggesting T-cells to RV could trigger islet autoimmunity by molecular
      mimicry. We therefore sought an association between RV infection and islet
      autoantibody markers in children at risk for diabetes who were followed from
      birth. There was a specific and highly significant association between RV
      seroconversion and increases in any of these antibodies: 86% of antibodies to IA
      2, 62% to insulin, and 50% to GAD first appeared or increased with increases in
      RV IgG or IgA. RV infection may therefore trigger or exacerbate islet
      autoimmunity in genetically susceptible children.

PMID- 10923634
TI  - Failure of physiological plasma glucose excursions to entrain high-frequency
      pulsatile insulin secretion in type 2 diabetes.
AB  - Insulin is released in high-frequency pulsatile bursts at intervals of 6-13 min.
      Intrapancreatic mechanisms are assumed to coordinate pulsatile insulin release,
      but small oscillations in plasma glucose concentrations may contribute further.
      To gain additional insight into beta-cell (patho)physiology, we explored the
      ability of repetitive small glucose infusions (6 mg/kg over 1 min every 10 min)
      to modify rapid pulsatile insulin secretion in 10 type 2 diabetic individuals
      (plasma glucose 9.3 +/- 1.0 mmol/l, HbA1c 7.9 +/- 0.5%, mean +/- SE) and 10
      healthy subjects. All subjects were investigated twice in randomly assigned
      order: during saline and during glucose exposure. Blood was collected every
      minute for 90 min to create a plasma insulin concentration time-series for
      analysis using 3 complementary algorithms: namely, spectral analysis,
      autocorrelation analysis, and approximate entropy (ApEn). During saline infusion,
      none of the algorithms were able to discriminate between diabetic and control
      subjects (P > 0.20). During glucose entrainment, spectral density peaks (SP) and
      autocorrelation coefficients (AC) increased significantly (P < 0.001), and ApEn
      decreased (P < 0.01), indicating more regular insulin time-series in the healthy
      volunteers. However, no differences were observed in the diabetic individuals
      between the glucose and saline conditions. Furthermore, in spite of identical
      absolute glucose excursions (approximately 0.3 mmol/l) glucose pulse entrainment
      led to a complete (SP: 4.76 +/- 0.62 [range 2.08-7.60] vs. 17.24 +/- 0.93 [11.70
      20.58], P < 0.001; AC: 0.01 +/- 0.05 [0.33-0.24] vs. 0.64 +/- 0.05 [0.35-0.83], P
      < 0.001) or almost complete (ApEn: 1.59 +/- 0.02 [1.48-1.67] vs. 1.42 +/- 0.05
      [1.26-1.74], P < 0.005) separation of the insulin time-series in diabetic and
      control subjects. Even elevating the glucose infusion rate in the diabetic
      subjects to achieve comparable relative (and hence higher absolute) glucose
      excursions (approximately 4.9%) failed to entrain pulsatile insulin secretion in
      this group. In conclusion, the present study demonstrates that failure to respond
      adequately with regular oscillatory insulin secretion to recurrent high-frequency
      and (near)-physiological glucose excursion is a manifest feature of beta-cell
      malfunction in type 2 diabetes. Whether the model will be useful in unmasking
      subtle (possible prediabetic) defects in beta-cell sensitivity to glucose drive
      remains to be determined.

PMID- 10923635
TI  - Linear correlation between beta-cell mass and body weight throughout the lifespan
      in Lewis rats: role of beta-cell hyperplasia and hypertrophy.
AB  - We determined the beta-cell replicative rate, beta-cell apoptosis, cross
      sectional beta-cell area, and pancreatic beta-cell mass throughout the entire
      postweaning lifespan (months 1, 3, 7, 10, 15, and 20) of Lewis rats. Beta-cell
      replication was progressively reduced in the initial months of life but remained
      stable after month 7 (month 1, 0.99 +/- 0.10%; month 3, 0.24 +/- 0.04%; month 7,
      0.12 +/- 0.02%; month 10, 0.14 +/- 0.02%; month 15, 0.10 +/- 0.03%; month 20,
      0.13 +/- 0.03%; analysis of variance [ANOVA], P < 0.001). Beta-cell apoptosis was
      low and did not change significantly from month 1 to 20 of life. Cross-sectional
      area of individual beta-cells increased progressively in the initial months,
      remained stable from month 7 to 15, and increased again on month 20. The
      estimated number of beta-cells per pancreas, calculated as the ratio of total
      beta-cell mass to individual beta-cell mass, tripled from month 1 to 7 but did
      not change significantly thereafter. Beta-cell mass increased approximately 8
      times from month 1 to 20 (month 1, 2.04 +/- 0.28 mg; month 20, 15.5 +/- 2.32 mg;
      ANOVA, P < 0.001) and showed a strong and significant linear correlation with
      body weight (r = 0.98, P < 0.001). In summary, we have shown that beta-cell
      replication was maintained throughout the lifespan in normal rats, clearly
      establishing that the beta-cell birth rate does not fall to 0, even in very old
      rats. Beta-cell mass increased throughout the lifespan, closely matching the
      increment in total body weight at any time point. This increment was selective
      for beta-cells, since the growth of the endocrine non-beta-cell mass was limited
      to the initial months of life. Both beta-cell hypertrophy and hyperplasia
      contributed to increased beta-cell mass in young animals, but only beta-cell
      hypertrophy was responsible for the increased beta-cell mass found in old
      animals. This study provides a global perspective for understanding the dynamics
      of beta-cell mass in young, adult, and aged animals.

PMID- 10923636
TI  - Soluble leptin receptor in serum of subjects with complete resistance to leptin:
      relation to fat mass.
AB  - Leptin resistance and obesity have been related to mutations of the leptin
      receptor gene in rodents and, recently, in a consanguineous family. The latter
      mutation results in a receptor lacking transmembrane and intracellular domains.
      Homozygous and heterozygous individuals with this mutation had serum leptin
      levels higher than expected, given their BMIs: 600, 670, and 526 ng/ml and 145,
      362, 294, 240, and 212 ng/ml, respectively. Their serum leptin was fractionated
      by gel filtration: >80% was present as a high-molecular size complex vs. 7.5% in
      the nonmutated sister. Western blot analysis showed a band at 146 kDa reacting
      specifically with an antibody directed against the leptin receptor ectodomain. In
      10 obese control subjects, as in the mutated patients, free leptin levels
      correlated with BMI (r = 0.70, P = 0.0011) and reflected fat mass, regardless of
      leptin receptor functioning. In the patients, bound leptin levels correlated with
      BMI (r = 0.99, P = 0.0002) and were related to the number of mutated alleles.
      These data demonstrate that the truncated receptor is secreted into blood and
      binds the majority of serum leptin, markedly increasing bound and total leptin.
      Free serum leptin was similarly correlated with BMI in the mutated and nonmutated
      obese individuals, providing evidence that the relationship between BMI and
      circulating free leptin is preserved in this family. This finding suggests that
      the leptin receptor itself may not be specifically involved in the control of
      leptin secretion, and it supports the concept of relative resistance to leptin in
      common obesity.

PMID- 10923638
TI  - Transient neonatal diabetes: widening the understanding of the etiopathogenesis
      of diabetes.
AB  - Transient neonatal diabetes (TND) is a rare type of diabetes that presents soon
      after birth, resolves by 18 months, and predisposes to diabetes later in life. A
      total of 30 patients were ascertained and investigated for aberrations of
      chromosome 6. A genotype/phenotype study was also performed. Genotypically, these
      patients can be classified into 4 etiologic groups. Group 1 had paternal
      uniparental isodisomy of chromosome 6 (11 cases, including 1 set of identical
      twins). Group 2 had a duplication involving chromosome band 6q24, which was
      paternal in origin where tested (4 sporadic cases and 7 familial cases from 2
      families). Group 3 consisted of 1 patient with a loss of methylation at a CpG
      island within the TND critical region (1 sporadic case). Group 4 had no
      identifiable rearrangement of chromosome 6 (7 sporadic cases). Most patients were
      growth retarded at birth, presented at a median age of 3 days, and recovered at a
      median age of 12 weeks. In group 2, 2 relatives of the TND patients who presented
      with type 2 diabetes and no early history of TND had inherited an identical
      duplication. An abnormality of chromosome 6 was identified in approximately 70%
      of sporadic TND cases and in all familial cases. No significant clinical
      differences were found between the 4 etiological groups. The study has broadened
      the clinical spectrum of TND to include type 2 diabetes presenting in later life
      with no neonatal presentation. The findings are consistent with an imprinted gene
      for diabetes mapping to 6q24, which we predict will have an important function in
      normal pancreatic development.

PMID- 10923637
TI  - Involvement of protein kinase C in human skeletal muscle insulin resistance and
      obesity.
AB  - This study was conducted to investigate the possible involvement of protein
      kinase C (PKC) and serine/threonine phosphorylation of the insulin receptor in
      insulin resistance and/or obesity. Insulin receptor tyrosine kinase activity was
      depressed in muscle from obese insulin-resistant patients compared with lean
      insulin-responsive control subjects. Alkaline phosphatase treatment resulted in a
      significant 48% increase in in vitro insulin-stimulated receptor tyrosine kinase
      activity in obese but not lean muscle. To investigate the involvement of PKC in
      skeletal muscle insulin resistance and/or obesity, membrane-associated PKC
      activity and the protein content of various PKC isoforms were measured in human
      skeletal muscle from lean, insulin-responsive, and obese insulin-resistant
      patients. Membrane-associated PKC activity was not changed; however, PKC-beta
      protein content, assayed by Western blot analysis, was significantly higher,
      whereas PKC-theta, -eta, and -mu were significantly lower in muscle from obese
      patients compared with muscle from lean control subjects. Incubation of muscle
      strips with insulin significantly increased membrane-associated PKC activity in
      muscle from obese but not lean subjects. PKC-delta, -beta, and -theta were
      translocated from the cytosol to the membrane fraction in response to insulin
      treatment. These results suggest that in skeletal muscle from insulin-resistant
      obese patients, insulin receptor tyrosine kinase activity was reduced because of
      hyperphosphorylation on serine/threonine residues. Membrane-associated PKC-beta
      protein was elevated under basal conditions, and membrane-associated total PKC
      activity was increased under insulin-stimulated conditions in muscle from obese
      insulin-resistant patients. Thus, we postulate that the decreased tyrosine kinase
      activity of the insulin receptor may be caused by serine/threonine
      phosphorylation by PKC.

PMID- 10923639
TI  - Influence of obesity and type 2 diabetes on gluconeogenesis and glucose output in
      humans: a quantitative study.
AB  - The contribution of gluconeogenesis (GNG) to endogenous glucose output (EGO) in
      type 2 diabetes is controversial. Little information is available on the separate
      influence of obesity on GNG. We measured percent GNG (by the 2H2O technique) and
      EGO (by 6,6-[2H]glucose) in 37 type 2 diabetic subjects (9 lean and 28 obese,
      mean fasting plasma glucose [FPG] 8.3 +/- 0.3 mmol/l) and 18 control subjects (6
      lean and 12 obese) after a 15-h fast. Percent GNG averaged 47 +/- 5% in lean
      control subjects and was significantly increased in association with both obesity
      (P < 0.01) and diabetes (P = 0.004). By multivariate analysis, percent GNG was
      independently associated with BMI (partial r = 0.27, P < 0.05, with a predicted
      increase of 0.9% per BMI unit) and FPG (partial r = 0.44, P = 0.0009, with a
      predicted increase of 2.7% per mmol/l of FPG). In contrast, EGO was increased in
      both lean and obese diabetic subjects (15.6 +/- 0.5 micromol x min(-1) x kg(-1)
      of fat-free mass, n = 37, P = 0.002) but not in obese nondiabetic control
      subjects (13.1 0.7, NS) as compared with lean control subjects (12.4 +/- 1.4).
      Consequently, gluconeogenic flux (percent GNG x EGO) was increased in obesity (P
      = 0.01) and markedly elevated in diabetic subjects (P = 0.0004), whereas
      glycogenolytic flux was reduced only in association with obesity (P = 0.05).
      Fasting plasma glucagon levels were significantly increased in diabetic subjects
      (P < 0.05) and positively related to EGO, whereas plasma insulin was higher in
      obese control subjects than lean control subjects (P = 0.05) and unrelated to
      measured glucose fluxes. We conclude that the percent contribution of GNG to
      glucose release after a 15-h fast is independently and quantitatively related to
      the degree of overweight and the severity of fasting hyperglycemia. In obese
      individuals, reduced glycogenolysis ensures a normal rate of glucose output. In
      diabetic individuals, hyperglucagonemia contributes to inappropriately elevated
      rates of glucose output from both GNG and glycogenolysis.

PMID- 10923640
TI  - Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are
      closely associated in human adipose tissue during morbid obesity.
AB  - In adipose tissue from both obese mice and humans, plasminogen activator
      inhibitor 1 (PAI-1) expression has been reported to be upregulated to levels of
      increased plasma PAI-1. This elevated expression has been shown to be partly
      controlled by tumor necrosis factor (TNF)-alpha in mice. In humans, increased PAI
      1 expression is associated with insulin resistance characterized by visceral fat
      accumulation. Therefore, the aim of this study was to investigate the expression
      pattern of PAI-1 and TNF-alpha (antigen and mRNA) in visceral human adipose fat
      in comparison with subcutaneous (SC) fat. Because transforming growth factor
      (TGF)-beta1 is a potent inducer of PAI-1 synthesis and has been shown to
      influence adipocyte metabolism, this work was extended to TGF-beta1
      quantification. A total of 32 obese individuals (BMI 42 +/- 6.8 kg/m2) were
      investigated. Freshly collected visceral adipose tissue did not exhibit a higher
      content of PAI-1 or TGF-beta1 than did SC tissue. Although most of the TNF-alpha
      values were at the detection limit of the methods, TNF-alpha antigen was 3-fold
      higher and TNF-alpha mRNA was 1.2-fold higher in visceral fat. The levels of
      tissue TGF-beta1 antigen correlated well with those of PAI-1 antigen, regardless
      of the fat depot studied (SC tissue: n = 21, r = 0.72, P = 0.0006; visceral
      tissue: n = 20, r = 0.49, P < 0.03), and they were both significantly associated
      with BMI. Conversely, no relationship was observed between the levels of TNF
      alpha and PAI-1 or TNF-alpha and BMI. Tissue PAI-1 levels were also significantly
      correlated with those of circulating PAI-1. These results describe, in severe
      obesity, a proportional increase in tissue PAI-1 and TGF-beta1 in visceral and SC
      tissues. This increased PAI-1 expression could be the result of tissue cytokine
      disturbances, such as elevated TGF-beta1 expression.

PMID- 10923641
TI  - Combined antioxidant and COMT inhibitor treatment reverses renal abnormalities in
      diabetic rats.
AB  - The development and progression of diabetic nephropathy is dependent on glucose
      homeostasis and many other contributing factors. In the present study, we
      examined the effect of nitecapone, an inhibitor of the dopamine-metabolizing
      enzyme catechol-O-methyl transferase (COMT) and a potent antioxidant, on
      functional and cellular determinants of renal function in rats with
      streptozotocin-induced diabetes. Administration of nitecapone to diabetic rats
      normalized urinary sodium excretion in a manner consistent with the dopamine
      dependent inhibition of proximal tubule Na,K-ATPase activity. Hyperfiltration,
      focal glomerulosclerosis, and albuminuria were also reversed by nitecapone, but
      in a manner that is more readily attributed to the antioxidant potential of the
      agent. A pattern of elevated oxidative stress, measured as CuZn superoxide
      dismutase gene expression and thiobarbituric acid-reactive substance content, was
      noted in diabetic rats, and both parameters were normalized by nitecapone
      treatment. In diabetic rats, activation of glomerular protein kinase C (PKC) was
      confirmed by isoform-specific translocation and Ser23 phosphorylation of the PKC
      substrate Na,K-ATPase. PKC-dependent changes in Na,K-ATPase phosphorylation were
      associated with decreased glomerular Na,K-ATPase activity. Nitecapone-treated
      diabetic rats were protected from these intracellular modifications. The combined
      results suggest that the COMT-inhibitory and antioxidant properties of nitecapone
      provide a protective therapy against the development of diabetic nephropathy.

PMID- 10923642
TI  - Promoter polymorphism T(-107)C of the paraoxonase PON1 gene is a risk factor for
      coronary heart disease in type 2 diabetic patients.
AB  - The serum enzyme paraoxonase (PON) protects LDLs from oxidative stress. We
      recently identified promoter polymorphisms of the PON gene that strongly affect
      gene expression and serum levels of the enzyme. The present study tested the
      hypothesis that promoter polymorphism T(-107)C could be a risk factor for
      vascular disease in type 2 diabetic patients by virtue of its ability to modulate
      serum concentrations of the antioxidant enzyme. The low-expressor genotype (TT)
      was associated with significantly lower serum PON concentrations, and it was over
      represented in type 2 diabetic patients with coronary heart disease (CHD) (TT vs.
      TC+CC: odds ratio [OR] 1.64 [95% CI 1.03-2.61], P < 0.05). The association of the
      low-expressor genotype with an increased risk of disease was independent of other
      risk factors, including the coding region Q191R polymorphism (OR 2.12 [95% CI
      1.19-3.70], P = 0.01). However, an interaction of the promoter polymorphism with
      the Q191R polymorphism, which was previously identified as an independent risk
      factor, was observed. The low-expressor promoter allele (-107T) associated with
      the high-risk 191R allele showed a lower-than-expected level of risk (OR 2.21 vs.
      the expected 4.76). The data are consistent with the hypothesis that low
      expression of the antioxidant enzyme PON increases the risk of CHD. Moreover, the
      promoter polymorphism appears to have a modulating effect on risk that is
      associated with the coding region polymorphism Q191R. This study indicates a
      strong genetic component to the antioxidant capacity of HDLs.

PMID- 10923643
TI  - Status of research funded by the American Diabetes Association.

PMID- 10923644
TI  - Receptor tyrosine phosphatases in axon growth and guidance.
AB  - The last 5 years has seen an explosion of evidence linking RPTPs to the
      regulation of axon growth and guidance. Important questions to be addressed
      include the ligand-receptor interactions involved in axon growth regulation, the
      signaling pathways controlled by RPTPs in neurons, and the manner in which
      different RPTPs within a class, and different classes of RPTPs, coordinate their
      functions to ensure appropriate axon growth. Are RPTPs signaling ligands,
      signaling receptors, or both? Do RPTPs function mainly by modifying adhesive
      preferences, or are they instructive in guidance decisions? Do specific types of
      RPTPs send specific signals to neurons, or do they work together to fine-tune
      levels of tyrosine phosphorylation? Whatever the outcome, it seems certain that
      the answers to these questions will come only from a combination of the powerful
      genetic approaches possible in Drosophila (and in mice) with the biochemical and
      cell biological approaches possible in the vertebrate systems.

PMID- 10923645
TI  - Dopamine and serotonin VMN release is related to feeding status in obese and lean
      Zucker rats.
AB  - Study of neurotransmitter role in food intake regulation in a leptin signaling
      deficient model, such as the Zucker rat, would benefit in the understanding of
      mechanisms of human obesity, in which leptin resistance is a common syndrome. We
      studied dopamine (DA) and serotonin (5-HT) concentrations in vivo in the
      ventromedial nucleus (VMN) of the hypothalamus, as they relate to eating after
      food deprivation in obese and lean 9-week-old male Zucker rats. DA and 5-HT
      concentrations were measured by HPLC via microdialysis before and during
      refeeding in 24-h food-deprived rats. Before food was provided, mean baseline DA
      and 5-HT levels were lower in obese than in lean rats (9.2 +/- 0.9 vs 15.1 +/-
      1.9 pg/10 microl, p < 0.01, and 0.68 +/- 0.05 vs 1.17 +/- 0.02 pg/10 microl, p <
      0.001, respectively). Food intake was accompanied by a decrease in DA levels in
      both obese and lean rats to 64% (p < 0.01) and 65% (p < 0.02) of their baseline
      levels respectively. 5-HT levels were significantly increased during eating by
      41% in obese and 35% in lean rats (p < 0.01) from the baseline levels. Thus in
      obese rats with altered leptin signaling we found an unaltered pattern of DA and
      5-HT release associated with food deprivation and refeeding, but with presence of
      their low levels. This points to an impaired postsynaptic monoaminergic action to
      produce an adequate metabolic response in obese Zucker rats in response to
      feeding state.

PMID- 10923647
TI  - Mutation analysis and association studies of the UCHL1 gene in German Parkinson's
      disease patients.
AB  - Recently, an Ile93Met substitution has been identified in the ubiquitin carboxy
      terminal hydrolase L1 (UCHL1) gene in a single German PD family with autosomal
      dominant inheritance. To determine whether mutations in the UCHL1 gene are
      causative for Parkinson's disease (PD) a detailed mutation analysis was performed
      in a large sample of German sporadic and familial PD patients. We found no
      disease-causing mutation in the coding region of the UCHL1 gene. Direct
      sequencing revealed six intronic polymorphisms in the UCHL1 gene. Analysis of an
      S18Y polymorphism in exon 3 of the UCHL1 gene in sporadic PD patients and
      controls showed carriers of allele 2 (tyrosine) significantly less frequent in
      patients with a reduced risk of 0.57 (CI = 0.36-0.88; p = 0.012, p(c) = 0.047,
      chi2 = 6.31). Our study shows that sequence variations in the coding region of
      UCHL1 are a rare event. A protective effect of a certain UCHL1 variant in the
      pathogenesis of sporadic PD is suggested, underlining the relevance of UCHL1 in
      neurodegeneration.

PMID- 10923646
TI  - p53-independent transient p21(WAF1/CIP1) mRNA induction in the rat brain
      following experimental traumatic injury.
AB  - The expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) mRNA after
      traumatic brain injury in rats was investigated using an in situ hybridization
      technique, along with regulating gene p53 and stress response gene hsp70 mRNA
      levels. At 3 h postinjury, p21(WAF1/CIP1) mRNA was markedly increased in the
      cortex, white matter, thalamus, CA2, a part of CA1,3 and dentate gyrus of the
      injured side. Hybridization signals remained elevated at 6 h in injured cortex
      and hippocampus and returned to the baseline by 24 h post-insult. On the other
      hand, p53 mRNA induction was not observed in any brain sections throughout the
      post-injury time course. Slight expression of hsp70 mRNA was detected in the
      injured cortex 3-6 h following injury and this was similar to the temporary
      pattern of p21(WAF1/CIP1) mRNA expression. This study showed p21(WAF1/CIP1) mRNA
      to be transiently induced after traumatic brain injury, independent of p53, this
      possibly being an early stress response to protect cells by arresting them in the
      cycle and allow DNA repair.

PMID- 10923648
TI  - Characterization of N,N(Me)2-Dmt-Tic-OH, a delta selective opioid dipeptide
      antagonist.
AB  - N,N(Me)2-Dimethyl-tyrosine-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid-OH
      (N,N(Me)2-Dmt-Tic-OH) is a very selective delta opioid dipeptide with elevated
      antagonist activity. We have radiolabelled this compound by catalytic tritiation
      of the N,N(Me)2-Dmt(3',5'-I2)-Tic-OH precursor. The ligand labelled rat brain
      membranes with a Kd value of 0.42 nM and a Bmax of 63.12 fmol/mg protein. The new
      tritiated ligand showed high affinity for the delta opioid receptor whereas its
      binding at mu and kappa opioid receptors was weak. N,N(Me)2-Dmt-Tic-OH was able
      to inhibit the agonist-stimulated binding of the non-hydrolysable GTP analogue
      ?35SGTPgammaS, thus attenuating the activation of G proteins via opioid
      receptors. This simple opioid dipeptide in both normal and labelled form may
      serve as a useful tool to study delta opioid receptors in vitro and in vivo.

PMID- 10923649
TI  - The two faces of perineuronal nets.
AB  - Perineuronal nets are extracellular structures enwrapping the soma and proximal
      dendrites of some neurons known to be parvalbumin immunoreactive. The composition
      of the nets is not completely known, but it can change between different neurons.
      We studied the heterogeneous composition of a specific component of perineuronal
      nets, the signaling molecule Janusin (or Tenascin R), by means of a double
      immunofluorescence using lectin from Wisteria floribunda as a general marker for
      perineuronal nets and an antibody against Janusin. The presence of two kinds of
      perineuronal nets, one rich in Janusin (the majority) and a second one devoid of
      this glycoprotein, indicates differential roles of these neurons, as well as
      differences in their afferents, or a difference in their functional state.

PMID- 10923650
TI  - Lesion of a higher-order song nucleus disrupts phrase level complexity in
      Bengalese finches.
AB  - Studies in zebra finches failed to demonstrate the involvement of the NIf, a
      higher-order song nucleus afferent to the HVc, in the production of learned song.
      The song of the Bengalese finch, a related species, has a higher level of
      temporal organization; multiple song phrases are organized into a song. We
      hypothesized that the NIf might control this complexity. To test this, we
      bilaterally lesioned the NIf in adult male Bengalese finches. The songs of birds
      with multi-phrase organization changed into simpler, mono-phrase songs. This is
      the first demonstration of the NIfs involvement in the production of birdsong.
      Zebra finch songs are syntactically simple and deterministic, and this might have
      caused the difficulty in demonstrating the function of the NIf in zebra finches.

PMID- 10923651
TI  - Refined mapping of CHRNA3/A5/B4 gene cluster and its implications in ADNFLE.
AB  - The chromosome 15q24 region, containing the CHRNA3/A5/B4 gene cluster, coding for
      the alpha3, alpha5 and beta4 subunits of neuronal nicotinic acetylcholine
      receptors, has been reported to be linked to autosomal dominant nocturnal frontal
      lobe epilepsy (ADNFLE) in one family. However, nor the gene nor the mutation
      involved have been identified. We report the refined mapping of CHRNA3/A5/B4
      cluster. Segregation analyses of CHRNA3/A5/B4 polymorphisms in families showing
      recombinations for 15q24 G?en?ethon STR markers allowed to position the cluster
      in a 0.6 cM interval, between STRs D15S1027 and D15S1005. This location is
      external to the 15q24-ADNFLE-linked region, therefore excluding the involvement
      of this cluster in the pathogenesis of ADNFLE in the 15q24-linked family.
      Moreover, these data provide more precise information for further linkage
      studies.

PMID- 10923652
TI  - Glibenclamide enhances cortical spreading depression-associated hyperemia in the
      rat.
AB  - We investigated the contribution of ATP-sensitive potassium channels (K(ATP)) and
      calcium-activated potassium channels (Kca2+) to cortical spreading depression
      (CSD)-associated hyperemia using the rat closed cranial window model. The peak
      CBF response was enhanced by 12 +/- 5, 13 +/- 4, and 28 +/- 8% (p<0.01) of the
      control with 10(-6), 10(-5) and 10(-4) mol/l glibenclamide (glyb), a K(ATP)
      antagonist, respectively. We also calculated the area under the CBF curve to
      fully represent the extent of hyperemia during CSD. The area increased by 30 +/-
      8 (p<0.05), 72 +/- 31 (p<0.05) and 88 +/- 20% (p<0.05) of the control with 10(
      6), 10(-5) and 10(-4) mol/l glyb, respectively. However, charybdotoxin (CTX), a
      Kca2+ antagonist showed no effect. The effect of glyb was inhibited by
      pretreatment with 5 mg/kg indomethacin. We conclude that activation of K(ATP),
      perhaps associated with neurons, plays an inhibitory role in the CSD-associated
      hyperemia via an indomethacin-sensitive mechanism.

PMID- 10923653
TI  - Low-[Mg2+]-induced Ca2+ fluctuations in organotypic hippocampal slice cultures.
AB  - We show here by whole field monitoring of free intracellular Ca2+ ([Ca2+]i),
      locally recorded field potential (fp) and external [Ca2+], that low-[Mg2+]
      induces seizure like events (SLEs) accompanied by simultaneous fluctuations of
      [Ca2+]i and [Ca2+]e in cultured hippocampal slices. Within a SLE, complex [Ca2+]e
      fluctuations are seen throughout phases of Ca2+ depletion (tonic) and Ca2+
      recovery (clonic) of the extracellular space. Information theory entropy-based
      analyses revealed strong asymmetric associations of [Ca2+]i and [Ca2+]e kinetics.
      By contrast, signal-associations between SLEs were found to be weak and of
      symmetric nature distinguishing seizure-like and interictal events by extensive
      coupling and decoupling of [Ca2+]i and [Ca2+]e fluctuations, respectively.

PMID- 10923654
TI  - Evidence for thoracolumbar spinal cord processing of inflammatory, but not acute
      colonic pain.
AB  - The lower bowel is innervated by visceral afferents projecting to the lumbosacral
      and thoracolumbar spinal segments. The present study tested the hypothesis that
      sensory processing from the normal colon occurs in the lumbosacral spinal cord
      with little or no activity in the thoracolumbar segments. Following colonic
      inflammation, viscerosensory processing in the thoracolumbar spinal cord is
      recruited, contributing to visceral hyperalgesia. A baseline visceromotor reflex
      to colorectal distention recorded in intact rats was eliminated following
      bilateral L6-S3 dorsal rhizotomies. The visceromotor reflex recovered to 29% of
      baseline following colonic inflammation. These results suggest that visceral
      hyperalgesia and referred pain in patients with lower bowel disorders partly
      result from novel viscerosensory processing in the thoracolumbar spinal cord.

PMID- 10923656
TI  - Characterization of optical intrinsic signals and blood volume during cortical
      spreading depression.
AB  - Cortical spreading depression (CSD) was imaged in vivo in a rodent model with
      optical intrinsic signals (OIS). This is the first study to identify a triphasic
      OIS response and to characterize the rate and timing of the response. The initial
      OIS phase had a highly uniform wavefront, which spread at a rate characteristic
      of CSD, 3.5 mm/min. Later phases were more diffuse and inhomogeneous. Blood
      volume changes, measured with intravascular fluorescent dye, correlated in time
      and location with the later phases of OIS response. This suggests that the
      inhomogeneity of the late OIS response may be due to complex residual hemodynamic
      contributions, as opposed to underlying cortical circuitry.

PMID- 10923655
TI  - Breathlessness in humans activates insular cortex.
AB  - Dyspnea (shortness of breath, breathlessness) is a major and disabling symptom of
      heart and lung disease. The representation of dyspnea in the cerebral cortex is
      unknown. In the first study designed to explore the central neural structures
      underlying perception of dyspnea, we evoked the perception of severe 'air hunger'
      in healthy subjects by restraining ventilation below spontaneous levels while
      holding arterial oxygen and carbon dioxide levels constant. PET revealed that air
      hunger activated the insular cortex. The insula is a limbic structure also
      activated by visceral stimuli, temperature, taste, nausea and pain. Like dyspnea,
      such perceptions underlie behaviors essential to homeostasis and survival.

PMID- 10923657
TI  - Prostaglandin E (EP) receptor subtypes and sleep: promotion by EP4 and inhibition
      by EP1/EP2.
AB  - Prostaglandin (PG) E2 reportedly augmented wakefulness when continuously infused
      into the third ventricle of the rat brain, whereas it promoted sleep when
      continuously infused into the subarachnoid space of the ventral surface zone of
      the rostral basal forebrain, which was designated previously as a PGD2-sensitive
      sleep-promoting zone (PGD2-SZ). In the present study, we investigated the effects
      of PGE (EP)-receptor agonists on sleep-wakefulness activities by infusing
      agonists into the third ventricle or into the subarachnoid space of the PGD2-SZ.
      Our results indicated that the waking effect is mediated by EP1 and EP2 receptors
      situating around the third ventricle, whereas the sleep-promoting effect is
      brought about mainly through activation of EP4 receptors located at or near the
      subarachnoid space of the PGD2-SZ.

PMID- 10923658
TI  - Perception of mirror symmetry reveals long-range interactions between orientation
      selective cortical filters.
AB  - We investigated perceptual interactions between orientation selective cortical
      filters using a task in which the observer was to detect mirror symmetry in
      briefly flashed visual patterns composed of oriented Gabor elements. On each
      trial, the Gabor patches were randomly placed in one half of the stimulus region,
      and symmetry was generated by reflecting the positions of the patch centers
      across the vertical axis. A prespecified proportion of patches were in mirror
      symmetrical positions with the remaining patches placed at random positions. The
      perception of mirror symmetry was measured for three stimulus conditions: (1)
      same orientation (i.e. all the local Gabor elements were either vertical or
      horizontal), (2) mixed matching (i.e. the orientations could be randomly both
      vertical and horizontal with the constraint that the orientations in a mirror
      symmetrical pair were matching), and (3) mixed opposing (i.e. the orientations
      were both vertical and horizontal, but in a mirror symmetrical pair they were
      always orthogonal). We found that the perception of global symmetry was poorer
      (thresholds were elevated) when the local orientations of feature pairs were
      orthogonal than when they were matched. This result is consistent with the
      properties of the neurons in the corpus callosum, which selectively interconnect
      cortical filters with identical orientation specificity.

PMID- 10923659
TI  - Correlation of intellectual impairment in Parkinson's disease with FDG PET scan.
AB  - This study investigated the relationship between regional glucose metabolism with
      intellectual impairment in patients with Parkinson's disease using statistical
      parametric mapping. Regional cerebral glucose metabolism using [18F]deoxyglucose
      (FDG) PET scans were performed on 10 patients with Parkinson's disease. We used
      the intellectual impairment score from the UPDRS. PET scans were analyzed with
      SPM96. Patients showed significant positive correlations with left limbic
      structures such as the cingulate gyrus, parahippocampal gyrus, and medial frontal
      gyrus. Patients showed significant negative correlations with associative
      neocortical posterior structures such as bilateral parietal and occipital gyrus.
      There were significant relationships between regional glucose metabolism and
      intellectual impairment.

PMID- 10923660
TI  - Cognitive sequence processing and syntactic comprehension in schizophrenia.
AB  - It has been repeatedly demonstrated that schizophrenic patients are impaired in
      the comprehension of sentences with complex syntax. We investigated the
      hypothesis that this syntactic comprehension impairment in schizophrenia is not a
      purely linguistic dysfunction, but rather the reflection of a cognitive sequence
      processing impairment that is revealed as task complexity increases. We tested 10
      schizophrenic patients using a standard measure of syntactic comprehension, and a
      non-linguistic sequence processing task, both of which required simple and
      complex transformation processing. Patients' performance impairment on the two
      tasks was highly correlated (r2 = 0.84), and there was a significant effect for
      complexity, independent of the task. These results are quite similar to those of
      aphasic patients with left hemisphere lesions. This suggests that syntactic
      comprehension deficits in schizophrenia reveal the dysfunction of cognitive
      sequence processing mechanisms that can be expressed both in linguistic and non
      linguistic sequence tasks.

PMID- 10923661
TI  - l-Menthol-induced [Ca2+]i increase and impulses in cultured sensory neurons.
AB  - We investigated the effects of l-menthol on cultured dorsal root ganglion (DRG)
      cells, instead of free nerve endings of sensory fibers. Using Fura-2
      microfluorimetry, we identified a few DRG neurons that showed an increase in
      intracellular free Ca2+ concentration ([Ca2+]i) in response to l-menthol. They
      made up only 10% of the neurons activated by a high K+ solution. l-Menthol
      induced the [Ca2+]i increase in a dose-dependent manner, with an EC50 of 37.9
      microM and a Hill coefficient of 0.97. A related compound, cyclohexanol, had no
      effect. When extracellular Ca2+ was removed, l-menthol did not induce the [Ca2+]i
      increase. Whole-cell current-clamp recordings revealed that l-menthol induced
      depolarization (13.2 mV, receptor potential) leading to impulses. We conclude
      that l-menthol induced the impulses through activation of menthol receptors in a
      small subset of the cultured sensory neurons.

PMID- 10923662
TI  - Chromosomes 4 and 13 in beta-carboline-induced seizures in mice: benzodiazepine
      binding.
AB  - Methyl beta-carboline-3-carboxylate (beta-CCM) is a ligand for the benzodiazepine
      (BZD) binding site of the GABA-A receptors with convulsive properties. We
      provided evidence for the involvement of a fragment of mouse chromosomes 4 and 13
      in beta-CCM-induced seizures in a previous paper. Here, we analyzed, through [3H]
      flumazenil binding, whether central BZD binding sites could be involved in the
      physiological processes underlying these differences of genetic sensitivities. In
      the JE/Le strain, where the effects of the chromosome 4 fragment can be analyzed,
      we found associations between [3H]-flumazenil binding and the convulsive action
      of beta-CCM. On the contrary, this no longer holds true in C3XtEso strain, where
      the effects of the chromosome 13 fragment were observed.

PMID- 10923663
TI  - Changes in spinal cord function caused by injuries at different levels of the
      lumbar spinal cord.
AB  - We examined the impact of spinal cord injury to a depth of 0.5 mm at L1-L2 (upper
      lumbar cord injury) and in L6-S1 (lower cord injury) in Wistar rats. Upper lumbar
      cord injury resulted in the disappearance of the motor evoked potential (MEP) of
      the gastrocnemius muscle during transcranial magnetic stimulation, while the
      threshold was decreased in rats with lower cord injury. During magnetic
      stimulation of L4-L5, the M-response threshold was decreased in rats with upper
      lumbar cord injury, while the amplitude was increased. In lower cord injury, the
      pattern of H-response recruitment curves differed from that in controls. Our
      results indicated that MEP and the spinal reflex are influenced not only by upper
      lumbar cord injury but also by lower cord injury.

PMID- 10923664
TI  - Is the face-sensitive N170 the only ERP not affected by selective attention?
AB  - We assessed the effect of directed attention on early neurophysiological indices
      of face processing, measuring the N170 event-related potential (ERP). Twelve
      subjects were tested on two tasks each in which they attended either to eyes only
      or to faces with eyes closed, presented within series of facial and control
      stimuli. Consistent with the ERP literature, N170 was recorded to facial stimuli
      at posterior temporal electrodes and a concomitant positive peak at the vertex,
      with latencies around 150 ms for faces and 174 ms for eyes. However, unlike fMRI
      studies, neither the latency nor the amplitude of the peaks were sensitive to the
      target/non-target status of either the eyes or the face stimuli. This suggests
      that early stages of face processing indexed by N 170 are automatic and
      unmodified by selective attention.

PMID- 10923665
TI  - The zitter mutant rat exhibits loss of D3 receptors with degeneration of the
      dopamine system.
AB  - Experimental studies of the regulation of the dopamine (DA) D3 receptor have
      utilized techniques causing massive depletions of the DA system. Zitter mutant
      rats exhibiting a heterogeneous loss of striatal DA innervation were examined for
      DA transporter (DAT) binding and DA D3 receptor number by autoradiography and
      compared with Sprague-Dawley rats. A significant loss of DAT binding was observed
      with the greatest in the lateral caudate-putamen (72% loss) and the least in the
      nucleus accumbens (45% loss). DA D3 receptors were reduced by > 70% in all
      regions, even in the nucleus accumbens that exhibited considerably smaller
      depletions of DAT binding, indicating that loss of D3 receptors may occur prior
      to massive loss of DA innervation.

PMID- 10923666
TI  - Antibody for human p75 LNTR identifies cholinergic basal forebrain of non-primate
      species.
AB  - 192-IgG is an antibody directed against the p75 low affinity nerve growth factor
      receptor in rats, whereas ME 20.4 was raised against the analogous protein in
      humans. Coupled to saporin, 192-IgG and ME 20.4 have been used to lesion basal
      forebrain neurons in rats and primates, respectively. We compared the cross
      reactivity of 192-IgG and ME 20.4 in the basal forebrain of rat, human, dog, cat,
      raccoon, pig, and rabbit. We found excellent species cross-reactivity of ME 20.4
      in dog, raccoon, cat, pig and rabbit. In contrast, 192-IgG did not label neurons
      in any species other than rat. Our findings suggest that ME 20.4-saporin could be
      used to produce cholinergic basal forebrain lesions in several non-primate
      species.

PMID- 10923667
TI  - Organization of cortico-cortical associative projections in a rat model of
      microgyria.
AB  - Microgyria was experimentally induced by focal freezing lesions of the frontal
      cortex in newborn rats. Adult microgyric animals received cortical injections of
      biotinylated dextran amine combined with NMDA, in order to obtain a Golgi-like
      retrograde labeling of cortico-cortical association neurons. Injections were
      performed either rostrally or caudally to the microgyric lesion. Results
      demonstrate that long-range association projections traveling across the zone of
      the microgyric lesion arise mainly from infragranular layers. In normal animals
      the same projections originate both from supragranular and infragranular layers.
      The analysis of single basal dendrites of layer 2/3 in microgyric animals
      demonstrates a simplified branching pattern, with a number of end points lower
      than in control animals. Potential implications for microgyria-associated
      epilepsy are discussed.

PMID- 10923668
TI  - Inhibition of glutamate uptake by Tx3-4 is dependent on the redox state of
      cysteine residues.
AB  - Glutamate transporters are essential for the homeostasis of glutamate and normal
      function of glutamatergic synapses. Their function was shown to be regulated by
      redox agents and dimerizations that involves redox changes of cysteine residues.
      Peptide neurotoxins are also known to be rich in cysteine residues that
      contribute to their activity and stability. Among them is the toxin Tx3-4, from
      the spider Phoneutria nigriventer, which is able to inhibit glutamate uptake in
      rat hippocampal synaptosomes. Based on results obtained with manipulation of the
      redox state of cysteine residues in synaptosomes and in Tx3-4, we suggest that
      the effect of this toxin on glutamate uptake is due to interactions that involve
      cysteines both in the toxin and in the transporters.

PMID- 10923669
TI  - 3-Methylindole alters both olfactory and trigeminal nasal mucosal potentials in
      rats.
AB  - Data from human studies imply that vanillin is an olfactory stimulant, whereas
      CO2 activates intranasal trigeminal nociceptors. We examined the effects of the
      olfactotoxin 3-methylindole (3-MI) on nasal mucosal potentials evoked by vanillin
      and CO2 in rats. A single i.p. administration of 300 mg/kg 3-MI altered both
      olfactory and trigeminal mucosal responses. Relative to amplitude values
      determined in non-3-MI-injected rats, the response to vanillin was reduced to 6%,
      7%, and 43%, and the response to CO2, recorded in the same rats, decreased to
      25%, 38%, and 51% at 4, 8 and 16 days post-3-MI, respectively. The results
      suggest that 3-MI affects both olfactory and trigeminal elements within the nasal
      mucosa.

PMID- 10923670
TI  - Activity in motor areas while remembering action events.
AB  - Episodic memory for simple commands is better following enacted than verbal
      encoding. This has been proposed to be due to the possibility to base retrieval
      on motor information. Here we used PET to test the hypothesis that motor brain
      areas show increased retrieval-related activity following enacted compared to
      verbal encoding. Brain activity was also monitored during retrieval after
      imaginary enactment during encoding. It was found that activity in the right
      motor cortex was maximal following encoding enactment, intermediate following
      imaginary encoding enactment, and lowest following verbal encoding. These
      findings provide support that one basis for the facilitating effect on memory
      performance of overt, and to a lesser degree covert, encoding enactment is the
      possibility to base retrieval on motor information.

PMID- 10923671
TI  - Object and spatial alternation tasks with minimal delays activate the right
      anterior hippocampus proper in humans.
AB  - Substantial evidence indicates that the hippocampus plays a critical role in long
      term declarative memory. In contrast, the role of the human hippocampus in
      working memory, particularly when information needs to be maintained only for a
      few seconds, remains controversial. Using PET, we show robust activation of the
      right anterior hippocampus proper during the performance of both object and
      spatial alternation tasks. Hippocampal activation emerged even though subjects
      only had to remember a single, simple stimulus over a minimum delay of 1 s. No
      hippocampal activation occurred when the delay was increased to 5 s. This
      suggests that the role of the hippocampus in working memory is not to maintain
      information across a delay interval. Instead, its activity reflects a more
      transient function during encoding and/or retrieval. These data are among the
      first observations to demonstrate human hippocampal involvement in working
      memory.

PMID- 10923672
TI  - Increased expression of alpha7 nAChR after transient hypoxia in PC12 cells.
AB  - We examined the effects of transient (6 h) hypoxia on nicotinic acetylcholine
      receptor (nAChR) subunit alpha7 expression in cultured PC12 cells, using RT-PCR
      and cytochemistry for alpha-bungarotoxin (alphaBTX) binding sites. The relative
      amount of alpha7 subunit mRNA compared with that before hypoxia decreased to 84%
      immediately after hypoxia, but then began to increase at 6 h after hypoxia,
      reaching 171% at 12 h. After this point, it decreased again to 81% at 48 h. Until
      6 h after hypoxia, cells appeared to shorten their neurites and form aggregates,
      without any accompanying remarkable change in alphaBTX binding sites compared
      with before hypoxia. However, at 12 h and 24 h after hypoxia, alphaBTX binding
      sites remarkably increased, whereafter cells resumed outgrowth of their neurites
      at 24-48 h. These findings suggested that nAChR subunit alpha7 was upregulated in
      both mRNA and protein levels in response to transient hypoxia/reoxygenation in
      PC12 cells.

PMID- 10923673
TI  - Synaptic localization of p39, a neuronal activator of cdk5.
AB  - The expression and kinase activity of cyclin dependent kinase 5 (cdk5) parallels
      the extent of neuronal differentiation. Cdk5 activity has been shown to be
      required for neurite outgrowth, cortical lamination and the overall development
      of the nervous system. p35 was identified as the first regulatory activator of
      cdk5 whose presence is required for cdk5 activation. p39 is a homolog of p35, and
      the only one identified in mammals thus far. We show here that p39 expression is
      mainly postnatal. In addition, we provide evidence for the presence of p39 at
      synaptic junctions through co-fractionation experiment, electron microscopy and
      immunostaining. The temporal and spatial expression of p39 indicate a possible
      role of the p39/cdk5 kinase at the synapse.

PMID- 10923674
TI  - A new member of the acid-sensing ion channel family.
AB  - Acid-sensing ion channels (ASICs) are members of the epithelial sodium channel
      (ENaC)-degenerin family of two-pass transmembrane segment protein subunits which
      form multimeric cation channels. Members of the ENaC-degenerin family are gated
      by stimuli as diverse as protons, peptides and mechanical distension. Here we
      describe a new member of the family, SPASIC or ASIC 4 (spinal cord ASIC) which is
      expressed throughout the central nervous system in an overlapping population of
      neurons that also express the ASIC subunit MDEG2. ASIC-4 which shows 44% identify
      with ASIC is developmentally regulated and expressed in a subset of sensory
      neurons as well as in the CNS. However, despite the strong homology with ASIC,
      the ASIC-4 transcript does not encode a proton gated cation channel.

PMID- 10923675
TI  - High frequency waking EEG: reflection of a slow ultradian rhythm in daytime
      arousal.
AB  - The ultradian dynamics of the human waking EEG was studied using a short visual
      fixation task repeated every 10 min throughout the daytime. The EEG spectra
      obtained from the tasks were assessed for time effect and ultradian periodicity.
      Fronto-central EEG high frequency powers (22.5-44.5 Hz) decreased at the time of
      the midafternoon vigilance dip (14.00-17.00 h) along with slight concomitant
      increases in parietal alpha (7.5-13.5 Hz) and delta (1-3 Hz) powers. A slow
      ultradian rhythm with a 3-4 h periodicity strongly modulated EEG power in all
      frequency bands between 1 and 44.5 Hz. The high frequency waking EEG may well
      reflect the activity of a brain arousal process underlying maintenance of the
      waking state probably throughout the 24 h cycle.

PMID- 10923676
TI  - Caenorhabditis elegans senses protons through amphid chemosensory neurons: proton
      signals elicit avoidance behavior.
AB  - Acidic pH is known to cause pain sensation through nociceptive neurons as well as
      taste transduction in mammals. Caenorhabditis elegans avoids an acidic
      environment (pH lower than approximately 4.0) formed by organic or inorganic
      acids. This avoidance behavior was dependent on multiple amphid chemosensory
      neurons, and inhibited by a mutation of capsaicin receptor homologue, and by the
      addition of amiloride and ruthenium red (inhibitors of proton-gated Na+ channels
      and capsaicin receptors, respectively). These results indicate that C. elegans
      recognizes protons as a nociceptive stimulus, through multiple neurons, which
      elicits avoidance behavior. It is of special interest that a system similar to
      that of mammalian signal transduction is responsible for this nematode's acid
      avoidance.

PMID- 10923677
TI  - Specific neurons of brain cortex and cerebellum are PIPPin positive.
AB  - We recently cloned a cDNA encoding an RNA-binding protein, that we called PIPPin,
      which is highly enriched in the rat brain and contains two putative double
      stranded RNA-binding domains (PIP1 and PIP2) and a central cold shock domain
      (CSD). Here we report that PIPPin is specifically enriched in some pyramidal
      neurons of the cerebral cortex and in the Purkinje cells of the cerebellum. We
      also show that PIPPin inhibits translation of H1(o) and H3.3 mRNA in a cell-free
      system. The results reported suggest that PIPPin down-regulates histone variant
      expression in the developing rat brain.

PMID- 10923678
TI  - Effects of neurotrophic factors on motoneuron survival following axonal injury in
      newborn rats.
AB  - Using two different lesion models, the spinal root avulsion and the distal nerve
      axotomy, the present study investigated effects of known neurotrophic factors on
      motoneuron survival in newborn rats. Results of the present study show that 100%
      of motoneurons in the lesioned spinal segment die at 1 week following root
      avulsion, and more than 80% of them die at 2 weeks following distal nerve
      axotomy. Local application of GDNF can rescue 92% of motoneurons up to 1 week
      from degeneration due to root avulsion and almost 100% of them up to 2 weeks from
      degeneration due to distal nerve axotomy. Local application of BDNF fails to
      prevent any motoneuron death in newborn rats following root avulsion, but it can
      rescue about 50% of motoneurons up to 2 weeks from degeneration due to distal
      nerve axotomy. CNTF and IGF-1 fail to prevent any motoneuron death following
      either distal nerve axotomy or root avulsion. Thus, comparing all the
      neurotrophic factors tested in this study, GDNF is most effective in preventing
      death of motoneurons following axonal injury in newborn rats.

PMID- 10923679
TI  - Opposite effects of short and continuous oestradiol replacement on CNS responses
      to hypoxic stress.
AB  - Oestrogen can alter neuroendocrine responses to stress but the evidence is
      conflicting. We examined the effects of a short-term 17beta-oestradiol surge
      versus a continuous 17beta-oestradiol replacement regime on neuroendocrine cell
      responses to hypoxia in the ovariectomized rat. Short-term oestradiol replacement
      significantly increased the number of Fos-positive SON and PVN OT cells and VLM
      A1 and C1 cells following hypoxia. In contrast, continuous oestradiol replacement
      significantly decreased the number of hypoxia-induced Fos-positive mPVN, PVN OT
      and VLM A1 and C1 and NTS C2 cells. We propose that the effects of oestradiol
      replacement on stress-induced neuroendocrine responses may be dependent on
      whether oestrogen levels are rising rapidly or remaining constant over a
      relatively long period.

PMID- 10923680
TI  - Pseudo-random procedures for rapid presentation rates using optical imaging and
      spectroscopy.
AB  - Optical imaging of rat barrel cortex has provided detailed spatio-temporal maps
      of functional cortical architecture. We describe an event-related procedure (ERP)
      for optical imaging based on selective signal averaging as reported by Burock et
      al., using an anti-correlative pseudo-random event sequence. The sequence used 1
      s vibrissal stimulation at 5 Hz, with an interevent interval of 2 s. This rapid
      presentation rate allows for greater statistical power per unit time, and allows
      for direct comparison of event-related studies with other imaging modalities. The
      spatio-temporal characteristics of single wavelength and spectrographic results
      were found to be comparable with those obtained by standard techniques, although
      a general lessening of haemodynamic response function (HRF) was noted. We also
      describe a method of locating barrel activity by spectral analysis of summed
      event data. Using this technique, the power spectrum of remitted light from the
      barrel region was found to peak within +/- 0.12 Hz of the inter-event interval
      frequency.

PMID- 10923681
TI  - Expression and localization of utrophin in differentiating PC12 cells.
AB  - To ascertain the role of utrophin in cultured neuronal cells, we investigated its
      expression and distribution along the NGF-induced differentiation of PC12 cells
      grown on different substrata. Utrophin mRNA was measured by RT-PCR assay and
      utrophin protein was quantified by immunoblot analysis. The distribution of
      utrophin and beta-dystroglycan was analyzed by confocal microscopy. We
      demonstrate that utrophin protein was increased 4-fold during differentiation of
      cells grown laminin. Concomitant with this up-regulation, utrophin was enriched
      at the growth cones in differentiating cells, where it co-localizes with beta
      dystroglycan. These data suggest the presence of a utrophin-beta-dystroglycan
      complex in PC12 cells that participates in the formation and/or stabilization of
      the growth cone-extracellular matrix adhesion.

PMID- 10923682
TI  - Functional activation of the left amygdala and hippocampus during associative
      encoding.
AB  - The human hippocampus is critical to episodic encoding, but the role of the
      amygdala in memory is less clear. Animal research suggests a role for the
      amygdala in associative memory, but this has not been examined systematically in
      humans. Using fMRI, we compared amygdala and hippocampus activation for seven
      healthy subjects during two visual encoding tasks: serially presented single
      faces and faces presented as pairs. Single faces activated bilateral hippocampi,
      but not the amygdala. Paired faces activated bilateral amygdala, but only the
      left hippocampus. Subtraction of the two conditions revealed greater activation
      within the left amygdala and hippocampus during paired face encoding, suggesting
      that associative encoding activates a left-lateralized limbic network including
      the hippocampus and amygdala.

PMID- 10923683
TI  - Hippocampal acetylcholine release correlates with spatial learning performance in
      freely moving rats.
AB  - To assess the activity of septohippocampal cholinergic neurons during the
      learning of a radial-arm maze task we measured changes in extracellular
      acetylcholine levels in the hippocampus by means of the vertical microdialysis
      technique. During the 12 days spent learning the spatial task the extracellular
      concentration of acetylcholine in the hippocampus was monitored while rats
      performed the test. One week before radial-arm maze training a guide cannula was
      implanted unilaterally in the hippocampus. On each day of testing a removable
      microdialysis probe was inserted through the guide cannula and the dialysate was
      collected during the test performance. The concentration of acetylcholine in the
      dialysate was detected by means of a high-performance liquid chromatograph
      coupled to an electrochemical detector. We found that hippocampal acetylcholine
      release progressively increased from 139% to 245% during the 12 days of radial
      maze learning and the magnitude of change in acetylcholine output was positively
      correlated with spatial memory performance, thus suggesting that changes in the
      functioning of these neurons are involved in learning.

PMID- 10923684
TI  - CEP-1347 increases ChAT activity in culture and promotes cholinergic neurone
      survival following fimbria-fornix lesion.
AB  - Recent evidence suggests that the activation of the Jun N-terminal kinase (JNK)
      signal transduction pathway may be important in neuronal responses to stresses
      such as trophic factor deprivation. Preventing the activation of JNK and
      expression of c-Jun may, therefore, be neuroprotective. Here, we report that the
      small molecule CEP-1347, which has been shown to inhibit the JNK signalling
      pathway, promotes cholinergic activity in cultured embryonic septal neurones. In
      vivo, we have shown that CEP-1347, administered either by sub-cutaneous (s.c.)
      injection or by continuous infusion, is partially neuroprotective, for
      cholinergic neurones in the medial septum, following fimbria-fornix transection.
      These data suggest that small molecules such as CEP-1347 may have beneficial
      effects in treating neurodegenerative diseases.

PMID- 10923685
TI  - Tropism of AAV-2 vectors for neurons of the globus pallidus.
AB  - A recombinant AAV-2 vector encoding the green fluorescent protein (gfp) under the
      control of the cytomegalovirus (CMV) promoter was injected into the striatum at
      varying antero-posterior coordinates. When the virus was delivered to the
      anterior part of the striatum, transduction efficiency was low and limited to the
      vicinity of the needle tract. In contrast, after injection into the posterior
      part of the striatum, in addition to a localized transduced area in the striatum,
      efficient and widespread transduction was observed at distance from the injection
      site, in the globus pallidus. In the latter case, labelled cells were also
      detected in the internal capsule and in the stria terminalis. The number of
      transduced cells in the striatum increased up to I month and then decreased
      whereas in the globus pallidus, transduction was maximal as early as 2 weeks post
      injection. In the striatum and in the globus pallidus, the labelled cells had a
      neuron-like morphology. In contrast, in the internal capsule, labelled cells had
      a glial-like morphology.

PMID- 10923686
TI  - Infusion of flesinoxan into the amygdala blocks the fear-potentiated startle.
AB  - In a previous study it was demonstrated that flesinoxan, a selective serotonin (5
      HT)1A receptor agonist, had anxiolytic properties in the fear-potentiated startle
      paradigm. The present study investigated the putative site of action of
      flesinoxan in this paradigm. Flesinoxan infused either into the dorsal raphe
      nucleus or the median raphe nucleus did not affect startle potentiation.
      Bilateral infusion of flesinoxan into the central nucleus of the amygdala on the
      other hand, dose-dependently blocked the fear-potentiated startle response. These
      data indicate that flesinoxan exerts it anxiolytic effects in the fear
      potentiated startle paradigm via the central nucleus of the amygdala, whereas the
      dorsal and median raphe nuclei are not directly involved in this process.

PMID- 10923687
TI  - Modulation of cortical excitability during action observation: a transcranial
      magnetic stimulation study.
AB  - Paired-pulse transcranial magnetic stimulation (TMS) was used to examine changes
      in cortical excitability during action observation. We stimulated the left
      primary motor cortex (M1) of eight healthy volunteers during rest, observation of
      handwriting and observation of arm movements. Motor evoked potentials (MEP) were
      recorded from the first dorsal intereosseous (FDI) and biceps (BIC) muscles. Our
      results showed that action observation induced a facilitation of the MEP
      amplitude evoked by the single test stimulus and reduced intracortical inhibition
      and facilitation at 3 ms and 12 ms interstimulus intervals (ISIs), respectively,
      during paired-pulse stimulation. These changes were specific for the muscle
      involved in the observed action. Our study presents further evidence that motor
      excitability is significantly modified when the subject observes an action
      performed by another individual.

PMID- 10923688
TI  - cAMP delays beta-amyloid (25-35) induced cell death in rat cortical neurons.
AB  - Beta-amyloid (A beta) accumulation is believed to contribute to neuronal cell
      death in Alzheimer's disease. To understand the role of cAMP in the regulation of
      A beta induced cell death, we used 8-chlorophenylthio-cAMP (8-CPT-cAMP, a cAMP
      analog) to raise intracellular cAMP levels. Exposure of rat cortical neurons to A
      beta(25-35) resulted in a gradual increase in lactate dehydrogenase (LDH) over 48
      h, which was preceded by a transient elevation in caspase-3-like activity. In the
      presence of 8CPT-cAMP, both caspase-3 activity and LDH release was significantly
      reduced. These data suggest that elevation of intracellular cAMP levels attenuate
      A beta-induced neurotoxicity and may delay or prevent the onset of A beta-induced
      neurodegeneration.

PMID- 10923689
TI  - Caspase inhibitors block zinc-chelator induced death of retinal ganglion cells.
AB  - Zinc-chelating agents, including ethambutol and its metabolite
      2,2'(ethylenediamino)-dibutyric acid (EDBA) are toxic to retinal ganglion cells
      through a glutamate dependent mechanism. We explored whether such cell death was
      mediated through the caspase family of cysteine proteases. Retinal cultures were
      treated with EDBA alone, or EDBA plus a variety of known caspase inhibitors, and
      ganglion cell viability was assayed. EDBA killed 20-30% of ganglion cells. A
      general caspase inhibitor, BAF, prevented EDBA induced ganglion cell death.
      Specific inhibitors of caspase-3 and caspase-6 showed a similar ability to BAF in
      preventing EDBA mediated ganglion cell loss, whereas inhibitors of caspase-8 and
      caspase-9 were not able to rescue EDBA treated ganglion cells. A caspase-1,4
      inhibitor was less effective than BAF. These studies show that a caspase mediated
      mechanism of apoptosis accents for a portion of EDBA mediated retinal ganglion
      cell death. This toxicity was mediated by downstream effector caspases, 3 and 6.
      Caspase inhibitors may prevent ganglion cell death secondary to ethambutol
      treatment.

PMID- 10923690
TI  - Guanine nucleotides block agonist-driven 45Ca2+ influx in chick embryo retinal
      explants.
AB  - AMPA (EC50 = 1.0 x 10(-6) M) and NMDA (EC50 = 1.3 x 10(-4) M) trigger 45Ca2+
      influx in 13-day chick embryonic retinal explants. This agonist-driven cationic
      flux is specifically inhibited by typical competitive antagonists, such as 6,7
      dinitroquinoxaline-2,3-dione (DNQX) and 2-amino-7-phosphonoheptanoate (AP7),
      respectively. Guanine nucleotides, with different degrees of phosphorylation,
      namely 5'-GMP, guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS), guanosine 5'-O-(3
      thiotriphosphate) (GTPgammaS) and 5'-guanylyl-imidodiphosphate (GppNHp), are also
      efficient blockers of 45Ca2+ influx. These results confirm the antagonistic
      behavior of guanine nucleotides towards ionotropic glutamate receptors and
      suggest a convenient experimental approach for screening of novel agonists and
      antagonists.

PMID- 10923691
TI  - Dose-dependent neuroprotection with tiagabine in a focal cerebral ischemia model
      in rat.
AB  - Enhancement of the inhibitory activity of GABA may protect ischemic neurons. We
      evaluated the neuroprotective effect of tiagabine, a novel GABA agonist, in
      reversible focal cerebral ischemia rats subjected to 2h middle cerebral artery
      (MCA) occlusion. Tiagabine was given at 10, 20 and 40 mg/kg, i.p., 2 h after the
      onset of reperfusion. We found that post-ischemia treatment with tiagabine
      improved neurobehavioral outcome and reduced brain infarction volume in a dose
      dependent manner. The data suggest that post-ischemic administration of tiagabine
      is neuroprotective in the focal cerebral ischemia model.

PMID- 10923692
TI  - Evidence for fusion and segregation induced by 21 Hz multiple-digit stimulation
      in humans.
AB  - Subjects were trained to detect changes in the frequency of 21 Hz tactile
      stimulation applied to digits 2 + 3 + 4 (fusion group) or 2 + 4 (segregation
      group) of the right hand. The 21 Hz steady-state response for digit 3 was
      measured by 64 channel EEG on mapping trials before and after training.
      Discrimination improved over 3 days, confirming that subjects attended to the
      training stimuli. The 21 Hz response was larger on training than on mapping
      trials, indicating sensitivity of the response to the strength of cortical
      activation. Under these conditions the 21 Hz response for digit 3 decreased after
      training in both groups on day 1. On day 3 this effect reversed in a subset of
      fusion subjects while segregation continued to yield decreases. The findings
      suggest that somatosensory representations are dynamically modified by the
      sensory input experienced on a task.

PMID- 10923693
TI  - The face-specific N170 component reflects late stages in the structural encoding
      of faces.
AB  - To investigate which stages in the structural encoding of faces are reflected by
      the face-specific N170 component, ERPs (event-related brain potentials) were
      recorded in response to different types of face and non-face stimuli. The N170
      was strongly attenuated for cheek and back views of faces relative to front and
      profile views, demonstrating that it is not merely triggered by head detection.
      Attenuated and delayed N170 components were elicited for faces lacking internal
      features as well as for faces without external features, suggesting that it is
      not exclusively sensitive to salient internal features. It is suggested that the
      N170 is linked to late stages of structural encoding, where representations of
      global face configurations are generated in order to be utilised by subsequent
      face recognition processes.

PMID- 10923694
TI  - Gamma band response in children is related to task-stimulus processing.
AB  - The present study described the functional characteristics of early phase-locked
      electroencephalographic gamma band (30-60 Hz) responses (GBRs) in 9- to 12-year
      old healthy children. GBRs were elicited in an auditory selective-attention task.
      Target stimuli required motor responding when presented to the right or to the
      left (attended side). Effects of stimulus type relevance and attended side were
      evaluated for GBR power and phase-locking within 0-120 ms. GBRs in children were
      frontally distributed, were larger and better phase-locked to targets relative to
      non-targets, but did not depend on the attended side. These results demonstrate
      that the auditory GBR is related to task-stimulus processing and imply that early
      target selection in children is guided by a sensory or sensorimotor preparatory
      set, rather than by an internal attentional focus to the side of stimulation.

PMID- 10923695
TI  - Methylmalonate administration decreases Na+,K+-ATPase activity in cerebral cortex
      of rats.
AB  - Buffered methylmalonate (MMA) was injected s.c. into rats twice a day at 8 h
      intervals from 5 to 25 days of age (chronic treatment), or into 10-day-old rats
      three times a day at 1 h intervals (acute treatment). Control rats received
      saline in the same volumes. Na+,K+-ATPase and Mg2+-ATPase activities were
      determined in the synaptic plasma membranes from cerebral cortex of rats. Na+,K+
      ATPase activity was reduced by 30-40% in MMA-treated rats, whereas Mg2+-ATPase
      activity was not. In contrast, MMA at final concentrations ranging from 0.1 to
      2.0 mM had no in vitro effect on these enzyme activities. However, when brain
      homogenates were incubated with 2 mM MMA before membrane preparation, Na+,K+
      ATPase activity was decreased by 44%. Furthermore, this reduction was totally
      prevented by the simultaneous addition of glutathione and MMA, suggesting that
      oxidation of thiol groups or other oxidative damage to the enzyme could be
      responsible for this effect.

PMID- 10923696
TI  - TS+OCD-like neuropotentiated mice are supersensitive to seizure induction.
AB  - Seizures can be induced by systemic dopamine D1 receptor agonists or by cortical
      limbic neurostimulation non-selectively. Seizures are also often associated with
      tics and compulsions, which likewise involve cortical-limbic hyperactivity. To
      determine if selective potentiation of cortical-limbic D1 receptor-expressing
      (D1+) neurons increases seizure susceptibility, we administered
      pentylenetetrazole (PTZ) to mice that express a neuropotentiating transgene only
      in a glutamatergic, cortical-limbic subset of D1+ neurons (D1CT-7 line). These
      mice exhibited increased PTZ-dependent seizure incidence, onset rate and
      intensity. Because D1CT-7 mice also exhibit tic+compulsion-like behaviors, this
      implies that glutamatergic hyperactivity induced by cortical-limbic D1+
      neuropotentiation facilitates not only epilepsy but also tics and compulsions.
      This suggests a dopamine-regulated glutamatergic basis for all three states and
      may explain why they often co-exist in humans.

PMID- 10923697
TI  - Greater song complexity is associated with augmented song system anatomy in zebra
      finches.
AB  - We revisited the relationship between brain anatomy and song behavior in zebra
      finches. Consistent with previous studies in other songbirds, we find that
      differences in volume of the telencephalic song control nucleus HVc is predictive
      of differences in repertoire size and phrase duration in zebra finches. We extend
      the study of brain and behavior correlations in song birds by showing that
      repertoire size in zebra finches can be predicted by variance in several brain
      nuclei, providing the first demonstration that volumetric differences across
      multiple components of a neural network are predictive of song behavior.

PMID- 10923698
TI  - Different functions of vicilin and legumin are reflected in the histopattern of
      globulin mobilization during germination of vetch (Vicia sativa L.).
AB  - The temporal and spatial patterns of storage-globulin mobilization were
      immunohistochemically pursued in the embryonic axis and cotyledons of vetch seed
      (Vicia sativa L.) during germination and early seedling growth. Embryonic axes as
      well as cotyledons of mature seeds contain protein bodies with stored globulins.
      Prevascular strands of axes and cotyledons, the radicle and epidermal layers of
      axis organs were nearly exclusively stained by vicilin antibodies whereas the
      cotyledonous storage mesophyll gave similar staining for vicilin and legumin.
      Globulin breakdown started locally where growth and differentiation commenced in
      the axis. There, vicilin mobilization preceded legumin mobilization. Thus vicilin
      represents the initial source of amino acids for early growth and differentiation
      processes in vetch. Legumin presumably only serves as a bulk amino acid source
      for subsequent seedling growth during postgerminative globulin degradation.
      During the first 2-3 d after the start of imbibition the axis was depleted of
      globulins whereas no decrease in immunostainability was detected in the
      cotyledons except in their vascular strands where immunostainability was almost
      completely lost at this time. Continuous vascular strands were established at the
      third day when globulin breakdown was finished in the axis but had just started
      in the cotyledon mesophyll. Protein mobilization proceeded in a small zone from
      the epidermis towards the vascular strands in the center of the cotyledons. In
      this zone the storage cells, which initially appeared densely packed with starch
      grains and protein bodies, concomitantly transformed into cells with a large
      central vacuole and only a thin cytoplasmic layer attached to the cell wall.
      These results agree well with the hypothesis that during the first 2 d after
      imbibition the axis is autonomous in amino acid provision. After the endogenous
      reserves of the axis are depleted and the conductive tissue has differentiated,
      globulins are mobilized in the cotyledons, suggesting that then the amino acid
      supply is taken over by the cotyledons. For comparison with other degradation
      patterns we used garden bean (Phaseolus vulgaris L) and rape (Brassica napus L.)
      as reference plants.

PMID- 10923699
TI  - Conditional identification of phosphate-starvation-response mutants in
      Arabidopsis thaliana.
AB  - Plants have evolved elaborate metabolic and developmental adaptations to low
      phosphorus availability. Biochemical responses to phosphate limitation include
      increased production and secretion of phosphate-acquisition proteins such as
      nucleases, acid phosphatases, and high-affinity phosphate transporters. However,
      the signal transduction pathways that sense phosphate availability and integrate
      the phosphate-starvation response in plants are unknown. We have devised a screen
      for conditional mutants in Arabidopsis thaliana (L.) Heynh. to dissect signaling
      of phosphate limitation. Our genetic screen is based on the facultative ability
      of wild-type Arabidopsis plants to metabolize exogenous DNA when inorganic
      phosphate is limiting. After screening 50,000 M2 seedlings, we isolated 22
      confirmed mutant lines that showed severely impaired growth on medium containing
      DNA as the only source of phosphorus, but which recovered on medium containing
      soluble inorganic phosphate. Characterization of nine such mutant lines
      demonstrated an inability to utilize either DNA or RNA. One mutant line, psr1
      (phosphate starvation response), had significantly reduced activities of
      phosphate-starvation-inducible isoforms of ribonuclease and acid phosphatase
      under phosphate-limiting conditions. The data suggest that a subset of the
      selected mutations impairs the expression of more than one phosphate-starvation
      inducible enzyme required for utilization of exogenous nucleic acids, and may
      thus affect regulatory components of a Pi starvation response pathway in higher
      plants.

PMID- 10923700
TI  - Three maize root-specific genes are not correctly expressed in regenerated caps
      in the absence of the quiescent center.
AB  - The quiescent center is viewed as an architectural template in the root apical
      meristem of all angiosperm and gymnosperm root tips. In roots of Arabidopsis
      thaliana (L.) Heynh., the quiescent center inhibits differentiation of contacting
      initial cells and maintains the surrounding initial cells as stem cells. Here,
      the role of the quiescent center in the development of the maize (Zeca mays L.)
      root cap has been further explored. Three maize root-specific genes were
      identified. Two of these were exclusively expressed in the root cap and one of
      them encoded a GDP-mannose-4,6-dehydratase. Most likely these two genes are
      structural, tissue-specific markers of the cap. The third gene, a putative
      glycine-rich cell wall protein, was expressed in the cap and in the root
      epidermis and, conceivably is a positional marker of the cap. Microsurgical and
      molecular data indicate that the quiescent center and cap initials may regulate
      the positional and structural expression of these genes in the cap and thereby
      control root cap development.

PMID- 10923701
TI  - The SCHIZOID gene regulates differentiation and cell division in Arabidopsis
      thaliana shoots.
AB  - Cell division and cell differentiation are key processes in shoot development.
      The Arabidopsis thaliana (L.) Heynh. SCHIZOID (SHZ) gene appears to influence
      cell differentiation and cell division in the shoot. The shz-2 mutant is notable
      in that distinct phenotypes develop, depending on the environment in which the
      plants are grown. When shz-2 mutants are grown in petri dishes, callus develops
      from the petiole and hypocotyl. In contrast, when the mutants are grown on soil,
      shoots appear externally stunted with malformed leaves. However, detailed
      examination of soil-grown mutants shows that the two phenotypes are related. Soil
      grown mutants form adventitious meristems, produce a large amount of vascular
      tissues and have aberrant cell divisions in the meristem. Cells with abnormal
      cell-division patterns were found in the apical and vascular meristems,
      suggesting SHZ influences cell division. Development of callus in petri dishes,
      development of adventitious meristems and aberrations in leaves on soil suggest
      that SHZ influences cell differentiation. The distinct, but related phenotypes on
      soil and in petri dishes suggests that SHZ normally functions to regulate
      differentiation and/or cell division in a manner that is responsive to
      environmental conditions.

PMID- 10923702
TI  - Light-dependent bicarbonate uptake and CO2 efflux in the marine microalga
      Nannochloropsis gaditana.
AB  - Inorganic carbon (Ci) uptake and efflux has been investigated in the marine
      microalga Nannochloropsis gaditana Lubian by monitoring CO2 fluxes in cell
      suspensions using mass spectrometry. Addition of H13CO3- to cell suspensions in
      the dark caused a transient increase in the CO2 concentration in the medium far
      in excess of the equilibrium CO2 concentration. The magnitude of this release was
      dependent on the length of time the cells had been kept in the dark. Once
      equilibrium between the Ci species had been achieved, a CO2 efflux was observed
      after saturating light intensity was applied to the cells. External carbonic
      anhydrase (CA) was not detected nor does this species demonstrate a capacity to
      take up CO2 by active transport. Photosynthetic O2 evolution and the release CO2
      in the dark depend on HCO3- uptake since both were inhibited by the anion
      exchange inhibitor, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS).
      The bicarbonate uptake mechanism requires light but can also continue for short
      periods in the dark. Ethoxyzolamide, a CA inhibitor, markedly inhibited CO2
      efflux in the dark, indicating that CO2 efflux was dependent upon the
      intracellular dehydration of HCO3-. These results indicate that Nannochloropsis
      possesses a bicarbonate uptake system which causes the accumulation of high
      intracellular Ci levels and an internal CA which maintains the equilibrium
      between CO2 and HCO3- and thus causes a subsequent release of CO2 to the external
      medium.

PMID- 10923703
TI  - Transient, oxidant-induced antioxidant transcript and enzyme levels correlate
      with greater oxidant-resistance in paraquat-resistant Conyza bonariensis.
AB  - The elucidation of mechanisms plants use to overcome oxidative stress is
      facilitated where there is intra-specific genetic variability. The differential
      induction of higher levels of mRNAs, cytosol and chloroplast antioxidant enzyme
      activities, and proteins occurred after sub-lethal paraquat treatment of the
      oxidant-resistant biotype of Conyza bonariensis (L.) Cronq. By 6 h after sub
      lethal paraquat treatment the activities of superoxide dismutase (EC 1.15.1.1),
      ascorbate peroxidase (EC 1.11.1.11), dehydroascorbate reductase (EC 1.8.5),
      monodehydroascorbate reductase (EC 1.6.5.4), and glutathione peroxidase (EC
      1.11.19) had increased, peaking at 24 h and then slowly reverting back to the
      basal level. Similarly, the levels of mRNAs encoding these enzymes were enhanced
      by 12 h and peaked at 18-24 h after sub-lethal paraquat treatment. The time
      courses of the transient elevation of both transcript and antioxidant enzyme
      levels correlated with a further transient 2.5- to 3.0-fold increase of paraquat
      resistance, which occurred only in the constitutively resistant biotype. The
      individual enzymes seem to be part of a coordinately controlled oxidant tolerance
      in the resistant biotype, utilizing oxidant-induced, increasingly abundant
      transcript levels, upon which more antioxidant enzymes were synthesized.

PMID- 10923704
TI  - Accumulation of a maize proteinase inhibitor in response to wounding and insect
      feeding, and characterization of its activity toward digestive proteinases of
      Spodoptera littoralis larvae.
AB  - The mpi gene encodes a maize proteinase inhibitor (MPI) protein whose mRNA
      accumulates in response to mechanical wounding. In this study, mpi gene
      expression in response to different types of damage was investigated. In
      mechanically damaged leaves of maize (Zea mays L.), mpi mRNA accumulation was
      affected by the degree of damage inflicted on the leaf. Consecutive wounds
      resulted in higher levels of mpi transcripts. The MPI protein was expressed in
      Escherichia coli and purified. Polyclonal antibodies were then produced and used
      to study MPI accumulation in insect-wounded and mechanically wounded maize
      leaves. When larvae of the lepidopteran insect Spodoptera littoralis were fed on
      maize leaves, MPI accumulated in tissues adjacent to the wound site. The level of
      inhibitor accumulation was higher in leaves chewed by larvae than in leaves that
      had been damaged mechanically. Longer feeding periods also resulted in higher
      levels of MPI accumulation. Additionally, the inhibitory properties of MPI toward
      mammalian and insect digestive serine proteinases were determined. Contrary to
      the majority of the plant proteinase inhibitors described, MPI is an inhibitor of
      mammalian elastase that only weakly inhibits mammalian chymotrypsin. However,
      both elastase and chymotrypsin-like activities from the larval midgut of S.
      littoralis were effectively inhibited by MPI. We discuss these results with
      regard to the function and evolution of plant proteinase inhibitors. The
      availability of a plant proteinase inhibitor which is able to inhibit the two
      types of insect digestive proteinase, elastase and chymotrypsin, might be useful
      for engineering protection against lepidopteran insect pests in transgenic
      plants.

PMID- 10923705
TI  - Import, processing, and assembly of the alpha- and beta-subunits of chloroplast
      pyruvate dehydrogenase.
AB  - Sequence comparisons were used to identify cDNAs potentially encoding the alpha-
      and beta-subunits of chloroplast pyruvate dehydrogenase. Coupled in-vitro
      transcription plus translation was used to synthesize radiolabeled pyruvate
      dehydrogenase alpha- and beta-subunit precursor proteins. When the precursors
      were incubated with intact pea (Pisum sativum L.) seedling chloroplasts in the
      presence of ATP, they were imported and proteolytically processed. In contrast,
      there was no import or processing of the precursors by isolated, intact pea
      seedling mitochondria. Monospecific antibodies to the recombinant pyruvate
      dehydrogenase alpha-subunit were additionally able to co-precipitate radiolabeled
      pyruvate dehydrogenase beta-subunit, indicating association between subunits
      after import and processing. Furthermore, size-exclusion chromatography was used
      to identify an alphabeta heterodimer that is an intermediate in the assembly of
      the native alpha2beta2 heterotetrameric enzyme.

PMID- 10923706
TI  - ATP-induced sucrose efflux from red-beet tonoplast vesicles.
AB  - Sucrose efflux from the vacuole of mobilizing red-beet (Beta vulgaris L.)
      hypocotyl cells was investigated using purified tonoplast vesicles. Tonoplast
      vesicle purity was assured by the immunoreactivity to antibodies raised against
      the vacuolar ATPase and by the strong inhibition exhibited by the H+-ATPase to
      bafilomycin-A and NO3-. Inhibition of the H+-ATPase by vanadate and azide was
      negligible. Sucrose was loaded into tonoplast vesicles by using the pH-jump
      method of energization. Addition of ATP to sucrose-loaded vesicles in the
      presence of bafilomycin-A resulted in efflux of a significant amount of sucrose.
      During ATP-induced sucrose efflux, bafilomycin-insensitive ATPase activity
      increased significantly with no increase in H+-translocating activity. The
      additional bafilomycin-A insensitive ATPase activity observed in sucrose-loaded
      vesicles was completely inhibited by vanadate as was the efflux of sucrose.
      Similar to vanadate, thapsigargin was also inhibitory to sucrose efflux and to
      the bafilomycin-A insensitive ATPase activity. The data indicate that vacuolar
      sucrose can be actively mobilized by a specific ATP-dependent efflux mechanism.

PMID- 10923707
TI  - Arbuscular mycorrhiza development regulates the mRNA abundance of Mtaqp1 encoding
      a mercury-insensitive aquaporin of Medicago truncatula.
AB  - The genome of the model legume Medicago truncatula Gaertn. was screened for the
      presence of genes encoding tonoplast intrinsic proteins, and a gene family was
      identified. The cDNA fragments of two members of the multigene family were cloned
      from roots inoculated with an arbuscular mycorrhizal fungus. Transcript
      accumulation in roots could be detected for both cDNA fragments, but only one
      gene was induced in the symbiosis when compared to non-mycorrhizal control roots.
      A full-length cDNA clone was obtained from the arbuscular-mycorrhiza-regulated
      gene, and injection of in-vitro-transcribed RNA into Xenopus oocytes revealed
      that the encoded protein MtAQP1 specifically facilitates water transport. The
      possible role of MtAQP1 in buffering osmotic fluctations in the highly
      compartmented vacuole of arbuscule cells is discussed.

PMID- 10923708
TI  - Characterization of prosystemin expressed in the baculovirus/insect cell system
      reveals biological activity of the systemin precursor.
AB  - Tomato (Lycopersicon esculentum Mill.) prosystemin in fusion with a viral signal
      peptide was expressed in Sf21 insect cell cultures after infection with
      recombinant baculoviruses. Prosystemin was purified from culture supernatants and
      its identity was confirmed by N-terminal sequence and mass-spectral analyses.
      Recombinant prosystemin was found to be equally active as compared to systemin in
      inducing the expression of wound-response genes in tomato plants. In cultured
      cells of L. peruvianum, prosystemin elicited a rapid alkalinization of the growth
      medium. The timing and dose-dependence of the alkalinization response were found
      to be identical for prosystemin and systemin, respectively. Prosystemin-triggered
      defense responses were inhibited by a competitive antagonist of systemin
      activity, indicating that the systemin sequence within the primary structure of
      prosystemin determines its activity.

PMID- 10923709
TI  - Inoculation and nitrate alter phytohormone levels in soybean roots: differences
      between a supernodulating mutant and the wild type.
AB  - The levels of different cytokinins, indole-3-acetic acid (IAA) and abscisic acid
      (ABA) in roots of Glycine max [L.] Merr. cv. Bragg and its supernodulating mutant
      nts382 were compared for the first time. Forty-eight hours after inoculation with
      Bradyrhizobium, quantitative and qualitative differences were found in the root's
      endogenous hormone status between cultivar Bragg and the mutant nts382. The six
      quantified cytokinins, ranking similarly in each genotype, were present at higher
      concentrations (30-196% on average for isopentenyl adenosine and dihydrozeatin
      riboside, respectively) in mutant roots. By contrast, the ABA content was 2-fold
      higher in Bragg, while the basal levels of IAA [0.53 micromol (g DW)(-1), on
      average] were similar in both genotypes. In 1 mM NO3(-)-fed Bragg roots 48 h post
      inoculation, IAA, ABA and the cytokinins isopentenyl adenine, and isopentenyl
      adenosine quantitatively increased with respect to uninoculated controls.
      However, only the two cytokinins increased in the mutant. High NO3- (8 mM)
      markedly reduced root auxin concentration, and neither genotypic differences nor
      the inoculation-induced increase in auxin concentration in Bragg was observed
      under these conditions. Cytokinins and ABA, on the other hand, were little
      affected by 8 mM NO3-. Root IAA/cytokinin and ABA/cytokinin ratios were always
      higher in Bragg relative to the mutant, and responded to inoculation (mainly in
      Bragg) and nitrate (both genotypes). The overall results are consistent with the
      auxin-burst-control hypothesis for the explanation of autoregulation and
      supernodulation in soybean. However, they are still inconclusive with respect to
      the inhibitory effect of NO3-.

PMID- 10923710
TI  - Minor vein structure and sugar transport in Arabidopsis thaliana.
AB  - Leaf and minor vein structure were studied in Arabidopsis thaliana (L.) Heynh. to
      gain insight into the mechanism(s) of phloem loading. Vein density (length of
      veins per unit leaf area) is extremely low. Almost all veins are intimately
      associated with the mesophyll and are probably involved in loading. In transverse
      sections of veins there are, on average, two companion cells for each sieve
      element. Phloem parenchyma cells appear to be specialized for delivery of
      photoassimilate from the bundle sheath to sieve element-companion cell complexes:
      they make numerous contacts with the bundle sheath and with companion cells and
      they have transfer cell wall ingrowths where they are in contact with sieve
      elements. Plasmodesmatal frequencies are high at interfaces involving phloem
      parenchyma cells. The plasmodesmata between phloem parenchyma cells and companion
      cells are structurally distinct in that there are several branches on the phloem
      parenchyma cell side of the wall and only one branch on the companion cell side.
      Most of the translocated sugar in A. thaliana is sucrose, but raffinose is also
      transported. Based on structural evidence, the most likely route of sucrose
      transport is from bundle sheath to phloem parenchyma cells through plasmodesmata,
      followed by efflux into the apoplasm across wall ingrowths and carrier-mediated
      uptake into the sieve element-companion cell complex.

PMID- 10923711
TI  - Decrease of phosphoribulokinase activity by antisense RNA in transgenic tobacco:
      definition of the light environment under which phosphoribulokinase is not in
      large excess.
AB  - To test the hypothesis that the contribution of phosphoribulokinase (PRK) to the
      control of photosynthesis changes depending on the light environment of the
      plant, the response of transgenic tobacco (Nicotiana tabacum L.) transformed with
      antisense PRK constructs to irradiance was determined. In plants grown under low
      irradiance (330 micromol m(-2) s(-1)) steady-state photosynthesis was limited in
      plants with decreased PRK activity upon exposure to higher irradiance, with a
      control coefficient of PRK for CO2 assimilation of 0.25 at and above 800 micromol
      m(-2) s(-1). The flux control coefficient of PRK for steady-state CO2
      assimilation was zero, however, at all irradiances in plant material grown at 800
      micromol m(-2) s(-1) and in plants grown in a glasshouse during mid-summer
      (alternating shade and sun 300-1600 micromol m(-2) s(-1)). To explain these
      differences between plants grown under low and high irradiances, Calvin cycle
      enzyme activities and metabolite content were determined. Activities of PRK and
      other non-equilibrium Calvin cycle enzymes fructose-1,6-bisphosphatase,
      sedoheptulose-1,7-bisphosphatase and ribulose-1,5-bisphosphate carboxylase
      oxygenase were twofold higher in plants grown at 800 micromol m(-2) s(-1) or in
      the glasshouse than in plants grown at 330 micromol m(-2) s(-1). Activities of
      equilibrium enzymes transketolase, aldolase, ribulose-5-phosphate epimerase and
      isomerase were very similar under all growth irradiances. The flux control
      coefficient of 0.25 in plants grown at 330 micromol m(-2) s(-1) can be explained
      because low ribulose-5-phosphate content in combination with low PRK activity
      limits the synthesis of ribulose-1,5-bisphosphate. This limitation is overcome in
      high-light-grown plants because of the large relative increase in activities of
      sedoheptulose-1,7-bisphosphatase and fructose-1,6-bisphosphatase under these
      conditions, which facilitates the synthesis of larger amounts of ribulose-5
      phosphate. This potential limitation will have maintained evolutionary selection
      pressure for high concentrations of PRK within the chloroplast.

PMID- 10923712
TI  - Zinc deficiency-induced phytosiderophore release by the Triticaceae is not
      consistently expressed in solution culture.
AB  - The effects of zinc (Zn) and iron (Fe) deficiencies on phytosiderophore (PS)
      exudation by three barley (Hordeum vulgare L.) cultivars differing in Zn
      efficiency were assessed using chelator-buffered nutrient solutions. A similar
      study was carried out with four wheat (Triticum aestivum L. and T. durum Desf.)
      cultivars, including the Zn-efficient Aroona and Zn-inefficient Durati. Despite
      severe Zn deficiency, none of the barley or wheat cultivars studied exhibited
      significantly elevated PS release rates, although there was significantly
      enhanced PS exudation under Fe deficiency. Aroona and Durati wheats were grown in
      a further study of the effects of phosphate (P) supply on PS release, using 100
      microM KH2PO4 as high P, or solid hydroxyapatite as a supply of low-release P.
      Phytosiderophore exudation was not increased due to P treatment under control or
      Zn-deficient conditions, but was increased by Fe deficiency. Accumulation of P in
      shoots of Zn- and Fe-deficient plants was seen in both P treatments, somewhat
      more so under the KH2PO4 treatment. Zinc-efficient wheats and grasses have been
      previously shown to exude more PS under Zn deficiency than Zn-inefficient
      genotypes. We did not observe Zn-deficiency-induced PS release and were unable to
      replicate the results of previous researchers. The tendency for Zn deficiency to
      induce PS release seems to be method dependent, and we suggest that all reported
      instances may be explained by an induced physiological deficiency of Fe.

PMID- 10923713
TI  - Inactivation of DNA replication origins by the cell cycle regulator,
      trigonelline, in root meristems of Lactuca sativa.
AB  - The effects of trigonelline (TRG) on the cell cycle in root meristems of Lactuca
      sativa L. were examined in the knowledge that TRG is a cell cycle regulator that
      causes cell arrest in G2, and prevents ligation of replicons in S-phase. The
      hypothesis was tested that continuous exposure to TRG would perturb DNA
      replication which, in turn, would lengthen the cell cycle and impair root
      elongation. Using DNA fibre autoradiography, mean replicon size was 31 and 13
      microm in the TRG (3 mM) and control treatments, respectively. Trigonelline also
      resulted in a lengthening of both S-phase and the cell cycle and a decrease in
      primary root elongation. Hence, replicon inactivation was responsible for the
      protracted S-phase. Trigonelline treatment also resulted in a 1.6-fold increase
      in fork rate (13.8 microm h(-1)) compared with the control (8.4 m h(-1)). The
      faster fork rate in the larger replicons is in accord with the highly significant
      positive relationship already established between fork rate and replicon size for
      various unrelated higher plants.

PMID- 10923714
TI  - The pattern of acropetal and basipetal cytoplasmic streaming velocities in Chara
      rhizoids and protonemata, and gravity effect on the pattern as measured by laser
      Doppler-velocimetry.
AB  - The spatial pattern of acropetal and basipetal cytoplasmic streaming velocities
      has been studied by laser-Doppler-velocimetry (LDV) in the positively gravitropic
      (downward growing) rhizoids of Chara globularis Thuill. and for the first time in
      the negatively gravitropic (upward growing) protonemata. The LDV method proved to
      be precise and yielded reproducible results even when tiny differences in
      velocities were measured. In the apical parts of the streaming regions of both
      cell types, acropetal streaming was faster than basipetal streaming. Starting at
      the apical reversal point of streaming, the velocity increased basipetally with
      the distance from that point and became fairly constant close to the basal
      reversal point; subsequently, the velocity decreased slightly acropetally as the
      apical reversal point was again approached. There was no change in velocity at
      the basal reversal point. However, at the apical reversal point there was an
      abrupt decrease in velocity. The pattern of the ratio of acropetal to basipetal
      streaming velocity (VR) was a function of the relative distance of the site of
      measurement from the apical reversal point rather than a function of the absolute
      distance. Upon inversion of the rhizoids, the VR decreased on average by 3.8% (+/
      0.4%), indicating that the effect of gravity on the streaming velocity was
      merely physical and without a physiological amplification. Rhizoids that had
      developed on the slowly rotating horizontal axis of a clinostat, and had never
      experienced a constant gravity vector, were similar to normally grown rhizoids
      with respect to VR pattern. In protonemata, the VR pattern was not significantly
      different from that in rhizoids although the direction of growth was inverse. In
      rhizoids, oryzalin caused the polar organization of the cell to disappear and
      nullified the differences in streaming velocities, and cytochalasin D decreased
      the velocity of basipetal streaming slightly more than that of acropetal
      streaming. Cyclopiazonic acid, known as an inhibitor of the Ca2+-ATPase of the
      endoplasmic reticulum, also reduced the streaming velocities in rhizoids, but had
      slightly more effect on the acropetal stream. It is possible that the endogenous
      difference in streaming velocities in both rhizoids and protonemata is caused by
      differences in the cytoskeletal organization of the opposing streams and/or
      loading of inhibitors (like Ca2+) from the apical/subapical zone into the
      basipetally streaming endoplasm.

PMID- 10923715
TI  - Ethylene promotes ethylene biosynthesis during pea seed germination by positive
      feedback regulation of 1-aminocyclo-propane-1-carboxylic acid oxidase.
AB  - Increased ethylene evolution accompanies seed germination of many species
      including Pisum sativum L., but only a little is known about the regulation of
      the ethylene biosynthetic pathway in different seed tissues. Biosynthesis of the
      direct ethylene precursor 1-aminocyclopropane-1-carboxylic acid (ACC), the
      expression of ACC oxidase (ACO), and ethylene production were investigated in the
      cotyledons and embryonic axis of germinating pea seeds. An early onset and
      sequential induction of ACC biosynthesis, accumulation of Ps-ACO1 mRNA and of ACO
      activity, and ethylene production were localized almost exclusively in the
      embryonic axis. Maximal levels of ACC, Ps-ACO1 mRNA, ACO enzyme activity and
      ethylene evolution were found when radicle emergence was just complete. Treatment
      of germinating seeds with ethylene alone or in combination with the inhibitor of
      ethylene action 2,5-norbornadiene showed that endogenous ethylene regulates its
      own biosynthesis through a positive feedback loop that enhances ACO expression.
      Accumulation of Ps-ACO1 mRNA and of ACO enzyme activity in the embryonic axis
      during the late phase of germination required ethylene, whereas Ps-ACS1 mRNA
      levels and overall ACC contents were not induced by ethylene treatment. Ethylene
      did not induce ACO in the embryonic axis during the early phase of germination.
      Ethylene-independent signalling pathways regulate the spatial and temporal
      pattern of ethylene biosynthesis, whereas the ethylene signalling pathway
      regulates high-level ACO expression in the embryonic axis, and thereby enhances
      ethylene evolution during seed germination.

PMID- 10923716
TI  - Importance of sequences adjacent to the terminal tripeptide in the import of a
      peroxisomal Candida tropicalis protein in plant peroxisomes.
AB  - The peroxisome targeting signal (PTS) required for import of the rat acyl-CoA
      oxidase (AOX; EC 1.3.3.6) and the Candida tropicalis multifunctional protein
      (MFP) in plant peroxisomes was assessed in transgenic Arabidopsis thaliana (L.)
      Heynh. The native rat AOX accumulated in peroxisomes in A. thaliana cotyledons
      and targeting was dependent on the presence of the C-terminal tripeptide S-K-L.
      In contrast, the native C. tropicalis MFP, containing the consensus PTS sequence
      A-K-I was not targeted to plant peroxisomes. Modification of the carboxy terminus
      to the S-K-L tripeptide also failed to deliver the MFP to peroxisomes while
      addition of the last 34 amino acids of the Brassica napus isocitrate lyase,
      containing the terminal tripeptide S-R-M, enabled import of the fusion protein
      into peroxisomes. These results underline the influence of the amino acids
      adjacent to the terminal tripeptide of the C. tropicalis MFP on peroxisomal
      targeting, even in the context of a protein having a consensus PTS sequence S-K
      L.

PMID- 10923717
TI  - Symplastic communication between the central cell and the egg apparatus cells in
      the embryo sac of Torenia fournieri Lind. before and during fertilization.
AB  - Various membrane-impermeable, water-soluble fluorescent tracers with different
      molecular weights were microinjected into the central cell of the embryo sac of
      Torenia fournieri Lind. before and during fertilization. Before anthesis, there
      was high symplastic permeability between the central cell and the egg apparatus
      cells. In this stage, fluorescent tracers up to 10 kDa could pass from the
      central cell into the egg apparatus cells, whereas those with larger molecular
      weight remained in the central cell. As the embryo sac matured, symplastic
      permeability decreased such that 2 d after anthesis only tracers less than 3 kDa
      could spread from the central cell into the egg cell. There appeared to be no
      symplastic permeability between the primary endosperm and zygote after
      fertilization, since tracers as small as 521 Da could not pass into the zygote in
      about half of the microinjected embryo sacs. This is the first report of a change
      in cell-to-cell communication among the cells of the female germ unit before and
      after fertilization.

PMID- 10923718
TI  - Transgenic Nicotiana tabacum and Arabidopsis thaliana plants overexpressing
      allene oxide synthase.
AB  - Allene oxide synthase (AOS), encoded by a single gene in Arabidopsis thaliana
      (L.) Heynh., catalyzes the first step specific to the octadecanoid pathway.
      Enzyme activity is very low in control plants, but is upregulated by wounding,
      octadecanoids, ethylene, salicylate and coronatine (D. Laudert and E.W. Weiler,
      1998, Plant J 15: 675-684). In order to study the consequences of constitutive
      expression of AOS on the level of jasmonates, a complete cDNA encoding the enzyme
      from A. thaliana was constitutively expressed in both A. thaliana and tobacco
      (Nicotiana tabacum L.). Overexpression of AOS did not alter the basal level of
      jasmonic acid; thus, output of the jasmonate pathway in the unchallenged plant
      appears to be strictly limited by substrate availability. In wounded plants
      overexpressing AOS, peak jasmonate levels were 2- to 3-fold higher compared to
      untransformed plants. More importantly, the transgenic plants reached the maximum
      jasmonate levels significantly earlier than wounded untransformed control plants.
      These findings suggest that overexpression of AOS might be a way of controlling
      defense dynamics in higher plants.

PMID- 10923719
TI  - Let us recruit the lung and keep an open mind.

PMID- 10923720
TI  - A role for plasma removal during sepsis?

PMID- 10923721
TI  - The continuing story of corticosteroids in the treatment of septic shock.

PMID- 10923722
TI  - Effects of periodic lung recruitment maneuvers on gas exchange and respiratory
      mechanics in mechanically ventilated acute respiratory distress syndrome (ARDS)
      patients.
AB  - OBJECTIVE: We wished to investigate whether volume recruitment maneuvers (VRMs)
      could improve alveolar recruitment and oxygenation in acute respiratory distress
      syndrome (ARDS) patients, ventilated at relatively low positive end-expiratory
      pressure (PEEP). SETTING: General intensive care unit (ICU) located in a teaching
      hospital. PATIENTS: 15 PEEP responder ARDS patients undergoing continuous
      positive pressure ventilation (CPPV) with sedation and muscle paralysis.
      INTERVENTIONS: We identified a low (9.4 +/- 3 cmH2O) and a high (16.0 +/- 2
      cmH2O) level of PEEP associated with target oxygenation values. Using a custom
      modified mechanical ventilator, we applied in random order three steps lasting 30
      min: (1) CPPV at the low PEEP level (CPPV(LO)); (2) CPPV at the high PEEP level
      (CPPV(HI)); (3) CPPV at low PEEP with the superimposition of periodic VRMs
      (CPPV(VRM)). VRMs were performed twice a minute by increasing PEEP to the high
      level for two breaths. Each brace of two breaths was spaced 30 seconds from the
      preceding one. MEASUREMENTS AND RESULTS: We measured gas exchange, hemodynamics,
      respiratory mechanics, and the end expiratory lung volume (EELV). Compared to
      CPPV(LO), CPPV(VRM) resulted in higher PaO2 (117.9 +/- 40.6 vs 79.4 +/- 13.6
      mmHg, P < 0.01) and EELV (1.50 +/- 0.62 vs 1.26 +/- 0.50 l, P < 0.05), and in
      lower venous admixture (Q(VA)/Q(T)) (0.42 +/- 0.07 vs 0.48 +/- 0.07, P < 0.01).
      During CPPV(HI), we observed significantly higher PaO2 (139.3 +/- 32.5 mmHg) and
      lower Q(VA)/Q(T) (0.37 +/- 0.08) compared to CPPV(LO) (P < 0.01) and to CPPV(VRM)
      (P < 0.05). CONCLUSIONS: VRMs can improve oxygenation and alveolar recruitment
      during CPPV at relatively low PEEP, but are relatively less effective than a
      continuous high PEEP level.

PMID- 10923723
TI  - The impact of respiratory variables on mortality in non-ARDS and ARDS patients
      requiring mechanical ventilation.
AB  - OBJECTIVES: Primarily, to determine if respiratory variables, assessed on a daily
      basis on days 1-6 after ICU admission, were associated with mortality in non-ARDS
      and ARDS patients with respiratory failure requiring mechanical ventilation.
      Secondarily, to determine non-respiratory factors associated with mortality in
      ARDS and non-ARDS patients. DESIGN: Prospective multicentre clinical study.
      SETTING: Seventy-eight intensive care units in Sweden and Iceland. PATIENTS: Five
      hundred twenty non-ARDS and 95 ARDS patients. MEASUREMENTS AND RESULTS:
      Potentially prognostic factors present at inclusion were tested against 90-day
      mortality using a Cox regression model. Respiratory variables (PaO2/FIO2, PEEP,
      mean airway pressure (MAP) and base excess (BE)) were tested against mortality
      using the model. Primary aim: in non-ARDS a low PaO2/FIO2 on day 1, RR (risk
      ratio) = 1.17, CI (95% confidence interval) (1.00; 1.36), day 4, 1.24 (1.02;
      1.50), day 5, 1.25 (1.02; 1.53) and a low MAP at baseline, 1.18 (1.00; 1.39), day
      2, 1.24 (1.02; 1.52), day 3, 1.33 (1.06; 1.67), day 6, 2.38 (1.11; 5.73) were
      significantly associated with 90-day death. Secondary aim: in non-ARDS a low age,
      RR = 0.77 (0.67; 0.89), female gender, 0.85 (0.74; 0.98), and low APS (acute
      physiologic score), 0.85 (0.73; 0.99), were associated with survival; chronic
      disease, 1.31 (1.12; 1.52), and non-pulmonary origin to the respiratory failure,
      1.27 (1.10; 1.47), with death. In ARDS low age, RR = 0.65 CI (0.46; 0.91), and
      low APS, 0.65 (0.46; 0.90), were associated with survival. CONCLUSIONS: No
      independent significant association was seen between 90-day mortality and degree
      of hypoxaemia, PEEP, MAP or BE for the first full week of ICU care in either ARDS
      or non-ARDS. In a sub-group of non-ARDS a lower PaO2/FIO2 and MAP tended to
      influence mortality where a significant association was seen for 3 of 7 study
      days. Age, gender, APS, presence of a chronic disease and a pulmonary/non
      pulmonary reason for the respiratory failure were associated with mortality in
      non-ARDS, while only age and APS showed a similar association in ARDS.

PMID- 10923724
TI  - Bioelectrical impedance analysis in estimating nutritional status and outcome of
      patients with chronic obstructive pulmonary disease and acute respiratory
      failure.
AB  - OBJECTIVE: To evaluate bioelectrical impedance analysis (BIA) in estimating the
      nutritional status and outcome of patients with chronic obstructive pulmonary
      disease (COPD) and acute respiratory failure (ARF) in comparison with
      measurements of anthropometric parameters and plasma levels of visceral proteins.
      DESIGN: Retrospective study. SETTING: A ten-bed intensive care unit (ICU) in a
      university teaching hospital. PATIENTS: 51 COPD patients with ARF in whom BIA
      data, anthropometric parameters, and measurements of visceral proteins were
      available. MEASUREMENTS AND RESULTS: BIA results in patients requiring mechanical
      ventilation (MV) vs. those who did not showed lower active cell mass (ACM; 37.5
      +/- 6.5% vs. 42.4 +/- 7.2% body weight, P = 0.01) and a higher extra
      /intracellular water volume ratio (ECW/ICW; 1.25 +/- 0.2 vs. 1.04 +/- 0.2, P =
      0.0001), suggesting a more severe alteration in the nutritional status among
      those on MV. Anthropometric data showed the opposite results, since body weight,
      body mass index (BMI), triceps skinfold thickness (TSF), and fat mass were
      significantly higher in the invasively ventilated patients, whereas middle-arm
      muscle circumference (MAMC) did not differ between the two groups. The marked
      inflation of the extracellular compartment (ECW, ECW/ICW) that was well shown by
      BIA in the invasively ventilated patients presumably lead to inaccurate
      anthropometric results (overestimation of TSF and fat mass, and erroneous measure
      of MAMC). A higher death rate (38% vs. 0%, P = 0.01) was observed in the patients
      with ACM depletion (ACM < or = 40.6% body weight, n = 26) than in those without
      ACM depletion (n = 25). Low albumin level (< 30 g/l) was associated with
      increased mortality (33% vs. 7%, P = 0.04), but the differences in the other
      biological and anthropometric parameters (prealbumin and transferrin levels, body
      weight, BMI, TSF, MAMC, fat mass, and fat-free mass) were not associated with
      mortality. CONCLUSION: This study suggests that the decrease in BIA-derived ACM
      is a good indication of malnutrition and of poor outcome in COPD patients with
      ARF.

PMID- 10923725
TI  - Late steroid therapy in primary acute lung injury.
AB  - OBJECTIVE: To investigate the effect of steroid treatment in the late phase of
      primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia.
      DESIGN: Retrospective study. SETTING: Multidisciplinary intensive care unit (ICU)
      in a university hospital. PATIENTS: Of 31 patients with primary ALI requiring
      mechanical ventilation for more than 10 days, 16 were treated with
      methylprednisolone and 15 served as controls. MEASUREMENTS AND RESULTS: Steroid
      and control groups were comparable regarding demographic data, APACHE II score,
      Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU.
      The mean start of steroid therapy was 9.7 days after establishment of respiratory
      failure, and values for control patients were registered on day 10. The PaO2/FiO2
      ratio improved significantly within 3 days after the start of steroid therapy,
      and MODS and C-reactive protein decreased concurrently. No differences in
      mortality, in length of ICU stay, or in length of mechanical ventilation were
      detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae
      pneumonia, beneficial change in physiological variables was evident. CONCLUSIONS:
      In patients with primary ALI, steroid therapy, started 10 days after the start of
      mechanical ventilation, improves gas exchange and is associated with a decrease
      in multiorgan dysfunction.

PMID- 10923726
TI  - Plasmapheresis combined with continuous venovenous hemofiltration in surgical
      patients with sepsis.
AB  - OBJECTIVE: To examine the effect of continuous venovenous hemofiltration (CVVHF)
      combined with plasmapheresis (TPE) in critically ill surgical patients after
      treatment of the septic focus. DESIGN: Observational pilot study. SETTING:
      University teaching hospital intensive care unit. INTERVENTIONS: TPE and CVVHF
      were administered 24 h after surgical and/or interventional treatment of septic
      focus. Arterial blood pressure, cardiac output, and systemic vascular resistance
      values were monitored. We examined the effect of the combined extracorporeal
      detoxification on outcome related to age, morbidity, organic failure rate, and
      initial APACHE II score. MEASUREMENTS AND RESULTS: Forty-three patients with
      sepsis were treated; 19 received TPE in combination with CVVHF, and 24 did not
      receive extracorporeal therapy. Overall mortality was 44.2%. In the therapy group
      mortality was lower (42.1 vs. 45.8%), but the primary organic failure rate was
      higher. The relationship between mortality and age was similar in the two groups.
      There was also no difference between the groups in the course of scores on APACHE
      II, multiple-organ failure, and sepsis severity. Only patients with an initial
      APACHE II score of 21-25 had a significant reduction in mortality after combined
      extracorporeal detoxification. Mortality of 17% in TPE/CVVHF patients with single
      (pulmonary) and double-organ failure (renal/pulmonary) was significantly lower
      (P < 0.0001) than in untreated patients. CONCLUSIONS: Reduction in mortality in
      single- and double-organ failure was as high as 28% in septic patients with
      combined extracorporeal detoxification. A prospective randomized trial in sepsis
      and double-organ failure should be projected.

PMID- 10923727
TI  - Endotoxaemia in patients with severe sepsis or septic shock.
AB  - OBJECTIVE: To examine the incidence and the bacteriological and clinical
      significance of endotoxaemia in ICU patients with severe sepsis or septic shock.
      DESIGN: Prospective review. SETTING: A 15-bed general ICU in a university
      hospital. PATIENTS: One hundred sixteen patients hospitalised in our ICU
      fulfilling Bone's criteria for severe sepsis or septic shock and with an
      available early endotoxin assay (chromogenic limulus assay). INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: The clinical characteristics of the population were:
      age 63.6 +/- 11.4 years; SAPS II: 45.4 +/- 15.6; mechanical ventilation: 72.4%;
      septic shock: 51.7% (n = 60); bacteraemia: 28.4% (n = 33); gram-negative bacteria
      (GNB) infection 47.4% (n = 55); ICU mortality: 39.6% (n = 46). Detectable
      endotoxin occurred in 61 patients (51.2%; mean level: 310 +/- 810 pg/ml). There
      was no relationship between detectable endotoxin and severity of infection at the
      moment of the assay. Endotoxaemia was associated with a higher incidence of
      bacteraemia (39.3% vs 16.3%; p = 0.01). There was a trend (p = 0.09) towards an
      association between positive endotoxin and gram-negative bacteraemia or GNB
      infection but this was non-significant. This relationship became significant only
      in the case of bacteraemia associated with GNB infection irrespective of the site
      of infection. CONCLUSION: Early detection of endotoxaemia appeared to be
      associated with GNB infection only in cases of bacteraemic GNB infection. Early
      endotoxaemia correlated neither to occurrence of organ dysfunction nor mortality
      in patients with severe sepsis or septic shock. This study suggests that the use
      of endotoxaemia as a diagnostic or a prognostic marker in daily practice remains
      difficult.

PMID- 10923728
TI  - Plasma cortisol is often decreased in patients treated in an intensive care unit.
AB  - OBJECTIVE: To investigate the prevalence of adrenal hypofunction, as assessed by
      plasma cortisol (p-cortisol) and its relationship to clinical events. DESIGN:
      Prospective, consecutive. SETTING: General intensive care unit in a university
      hospital. PATIENTS: Fifty-five patients (34 men and 21 women) were studied
      (surgery 40 patients, hemodialysis 5, ventilator treatment 45, sepsis 21).
      METHODS: Morning basal levels of p-cortisol were determined. Previous reports
      define adrenal insufficiency to be present if p-cortisol under stressful
      conditions is lower than either 400 or 500 nmol/l. The tetracosactoid test (250
      microg Synacthen) was performed in 16 patients and urinary 24-h excretion of
      cortisol in 24 (none on corticosteroid treatment). RESULTS: Median p-cortisol was
      550 nmol/l (range 20-1764). In 36% of patients p-cortisol was lower than 400
      nmol/l and in 47% lower than 500 nmol/l. There was a significantly increased
      probability (P < 0.05) of p-cortisol being below 400 nmol/l in patients admitted
      due to trauma or cerebral disorder and in patients on ventilator therapy or on
      mannitol. Thirty minutes after tetracosactoid administration p-cortisol response
      was lower than 200 nmol/l in 56% of the patients. CONCLUSIONS: Several patients
      had low p-cortisol and attenuated responses to tetracosactoid, indicative of
      adrenal insufficiency. There seem to be certain risk factors for adrenal
      hypofunction which may justify more frequent use of physiological doses of
      corticosteroid in selected patients.

PMID- 10923729
TI  - Control of fever by continuous, low-dose diclofenac sodium infusion in acute
      cerebral damage patients.
AB  - OBJECTIVES: The aim of this study was to assess the efficacy and safety of low
      doses of diclofenac sodium (DCF) in attaining normothermia with minimal major
      side effects in patients with acute cerebral damage. The study was designed to
      verify the adequate, prolonged antipyretic action of DCF infusion, to quantify
      its haemodynamic and cerebral impact and to assess any negative effect on renal
      and liver function. DESIGN: Retrospective, cohort study on prospectively
      collected data. SETTING: Intensive care unit (ICU) of a university hospital.
      PATIENT POPULATION: Five patients with subarachnoid haemorrhage and seven severe
      head-trauma victims with febrile illness of various infectious origin.
      INTERVENTIONS: Continuous i.v. infusion of a low dose (0.04 mg/kg/h) of DCF for
      48 h. MEASUREMENTS AND RESULTS: Systemic and cerebral haemodynamic data were
      collected at 4 h intervals for 8 h before diclofenac infusion and 48 h after.
      Renal and liver functions were monitored. Normothermia, defined as external
      temperature < 37.5 degrees Celsius (degrees C), was achieved in all cases.
      Intracranial pressure was significantly lowered and mean arterial pressure was
      unaffected, so cerebral perfusion pressure rose after DCF. Hepatic and renal
      function were not altered in the 48 h post DCF. Mean urinary output was preserved
      at high flow and was not influenced by DCF. CONCLUSIONS: Continuous infusion of
      low-dose DCF attained normothermia without any major cerebral or systemic side
      effects. Renal and liver functions were unaffected. Once normothermia was
      achieved, intracranial and cerebral perfusion pressure improved.

PMID- 10923730
TI  - The increase in CO2 production induced by NaHCO3 depends on blood albumin and
      hemoglobin concentrations.
AB  - OBJECTIVE: To evaluate the origin of H+ ions participating in the generation of
      CO2 coming from sodium bicarbonate infusion during metabolic acidosis. We
      hypothesized that these H+ ions come from a back-titration of the main non
      bicarbonate buffers present in the blood, i. e. the hemoglobin and the albumin,
      and thus postulated that the rate of CO2 release from a bicarbonate load is
      dependent on the concentration of these buffers. DESIGN: Prospective clinical and
      experimental study. SETTING: Surgical intensive care unit of a university
      hospital. PATIENTS AND MATERIAL: (1) Sixteen stable sedated and artificially
      ventilated critically ill patients with a mild base deficit. (2) Acidotic human
      blood (bicarbonate 5 mM, pH 7.0) of hematocrit 5, 10, 20 and 40% regenerated from
      a mixture of frozen fresh plasma and packed red blood cells. INTERVENTIONS: 
      PATIENTS: infusion of 1.5 mmol/kg sodium bicarbonate over 5 min. Regenerated
      blood: 25 mM sodium bicarbonate load. MEASUREMENTS AND RESULTS:  PATIENTS:
      continuous measurement of CO2 production (VCO2) on the expired gas using a
      metabolic monitor and arterial blood gas analysis before (T0), at the end (T5)
      and at 10, 30 and 60 min after the beginning of the bicarbonate infusion. The
      increase in VCO2 was 18 +/- 7% leading to a rise in PaCO2 from 39.6 +/- 2.3 at T0
      to 46.2 +/- 2.7 mmHg at T5. The increases in VCO2 and in PaCO2 were significantly
      correlated to the albumin (r = 0.73, p < 0.005 and r = 0.70, p < 0.005,
      respectively) and to the hemoglobin (r = 0.51, p < 0.05 and r = 0.65, p < 0.01,
      respectively) concentrations. Regenerated blood: gas analysis 1 min after the
      bicarbonate load. The increase in PCO2 was closely related to the hematocrit (Ht)
      of the blood as it was 15.9 +/- 7.5 mmHg for Ht 5%, 29.0 +/- 9.6 for Ht 10%, 44.2
      +/- 5.9 for Ht 20% and 71.0 +/- 3.5 for Ht 40% (n = 5 for each, p < 0.001).
      CONCLUSIONS: The importance of the release of CO2 from a bicarbonate load is
      dependent on the concentration of the blood non-bicarbonate buffers. It is
      therefore likely that the adverse effects of bicarbonate therapy linked to the
      CO2 generation are more important in patients with high blood albumin and
      hemoglobin concentrations.

PMID- 10923731
TI  - Acute renal failure following cardiopulmonary bypass: a changing picture.
AB  - OBJECTIVE: To assess the incidence of acute renal failure (ARF) developing
      perioperatively in adult patients requiring cardiopulmonary bypass surgery (CPB)
      and to make comparisons with data from the same institution published earlier.
      DESIGN: Prospective, observational. SETTING: Tertiary referral centre for
      cardiopulmonary medicine. PATIENTS AND PARTICIPANTS: All patients admitted to the
      intensive care unit (ICU) who developed ARF perioperatively necessitating
      continuous veno-venous haemofiltration (CVVH) during the 24 months January 1997
      December 1998. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Of 2337 adult
      patients undergoing cardiac surgery, 47 (2.0%) needed CVVH. Patients were
      excluded from analysis who underwent cardiac transplantation (n = 4), pericardial
      surgery (n = 3) or insertion of a left ventricular assist device (n = 1). Of the
      remaining 39, 21 patients died in ICU (53.8% mortality). Relatively more non
      survivors suffered from diabetes, hypertension and preoperative renal
      dysfunction. A previous report from our Unit revealed that, in 1989-90, 2.7% of
      all patients undergoing CPB required CVVH with an in-hospital mortality of 83%.
      The current study population were older (65.3 vs 56.0 years in 1990), and more
      severely ill as evidenced by a higher percentage of patients requiring redo (30%
      vs 8.6% in 1990) and emergency (50% vs 25.7% in 1990) surgery. CONCLUSIONS: The
      need for CVVH following CPB may be diminishing despite increased risk factors.
      ARF-associated mortality in these circumstances is falling.

PMID- 10923732
TI  - Pericardiocentesis: differential aspects of a common procedure.
AB  - OBJECTIVE: To evaluate the risk and effectiveness of pericardiocentesis in
      primary and repeat cardiac tamponade. DESIGN: Retrospective analysis. SETTING:
      Intensive care unit in a medical university hospital. PATIENTS: Sixty-three
      consecutively admitted patients with cardiac tamponade. INTERVENTIONS: In all
      patients pericardiocentesis was performed via the subxiphoid pathway after
      echocardiographic detection of the pericardial effusion. MEASUREMENTS AND
      RESULTS: There was no adverse event in patients undergoing primary
      pericardiocentesis, which was sufficient to resolve pericardial effusion in 51 of
      63 patients (81%). However, repeat pericardiocentesis necessitated by the
      recurrence of symptomatic pericardial effusion yielded suboptimal results in 10
      of 12 patients (83%). CONCLUSION: Pericardiocentesis is the treatment of choice
      for primary symptomatic pericardial effusion. In recurrent pericardial effusion
      surgical approaches appear to be preferable.

PMID- 10923733
TI  - The added value that increasing levels of diagnostic information provide in
      prognostic models to estimate hospital mortality for adult intensive care
      patients.
AB  - OBJECTIVE: To investigate in a systematic, reproducible way the potential of
      adding increasing levels of diagnostic information to prognostic models for
      estimating hospital mortality. DESIGN: Prospective cohort study. SETTING: Thirty
      UK intensive care units (ICUs) participating in the ICNARC Case Mix Programme.
      PATIENTS: Eight thousand fifty-seven admissions to UK ICUs. MEASUREMENTS AND
      RESULTS: Logistic regression analysis incorporating APACHE II score, admission
      type and increasing levels of diagnostic information was used to develop models
      to estimate hospital mortality for intensive care patients. The 53 UK APACHE II
      diagnostic categories were substituted with data from a hierarchical, five-tiered
      (type of condition required surgery or not, body system, anatomical site,
      physiological/pathological process, condition) coding method, the ICNARC Coding
      Method. The inter-rater reliability using the ICNARC Coding Method to code
      reasons for admission was good (kappa = 0.70). All new models had good
      discrimination (AUC = 0.79-0.81) and similar or better calibration compared with
      the UK APACHE II model (Hosmer-Lemeshow goodness-of-fit H = 18.03 to H = 26.77
      for new models versus H = 63.51 for UK APACHE II model). CONCLUSION: The UK
      APACHE II model can be simplified by extending the admission type and
      substituting the 53 UK APACHE II diagnostic categories with nine body systems,
      without losing discriminative power or calibration.

PMID- 10923734
TI  - Effect of hypothermia on ventilation in anesthetized, spontaneously breathing
      rats: theoretical implications for mechanical ventilation.
AB  - OBJECTIVE: To test if hypothermia, induced by a sustained pentobarbital
      anesthesia, in rats can reduce ventilatory demands without compromising pulmonary
      gas-exchange efficiency. DESIGN: Prospective study. SETTING: Research laboratory
      in a hospital. SUBJECTS: One group of 11 female Sprague Dawley rats.
      INTERVENTIONS: The rats were anesthetized with 45 mg/kg pentobarbital,
      tracheostomized and intubated; their femoral veins and arteries were cannulated.
      After surgery, anesthesia and fluid balance were maintained (10 mg/kg per h
      pentobarbital, and 5 ml/kg per h saline, i.v.). Rectal temperature, mean arterial
      blood pressure (MAP), and heart rate (HR) were continuously monitored. The
      respiratory variables and gas-exchange profiles were determined at 38 degrees C
      (normothermia), and during stepwise hypothermia at 37, 35, 33, 31 and 29 degrees
      C. The arterial pressure of carbon dioxide (PaCO2), pH and arterial pressure of
      oxygen (PaO2) during hypothermia were corrected at body temperature. MEASUREMENTS
      AND RESULTS: Graded systemic hypothermia, with maintained anesthesia, produced a
      strong correlation between reduction in the respiratory frequency and rectal
      temperature (r2 = 0.55; p < 0.0001; n = 66). The minute volume was significantly
      reduced, starting at 35 degrees C, without significant changes in the tidal
      volume (repeated measures of analyses of variance followed by Dunnett multiple
      comparisons test). No significant changes occurred in the PaCO2, pH, PaO2,
      hemoglobin oxygen saturation, the calculated arterial oxygen content and
      estimated alveolar-arterial oxygen difference during mild hypothermia (37-33
      degrees C). The PaO2, however, was significantly reduced below 31 degrees C. The
      MAP remained stable at different levels of hypothermia, whereas HR was
      significantly reduced below 33 degrees C. CONCLUSIONS: Mild hypothermia in rats,
      induced by a sustained pentobarbital anesthesia, reduces ventilation without
      compromising arterial oxygenation or acid-base balance, as measured at body
      temperature. Theoretically, our observations in spontaneously breathing rats
      imply that a combination of mild hypothermia with anesthesia could be safely
      utilized to maintain adequate ventilation, using relatively low minute
      ventilation. We speculate that such a maneuver, if applied during mechanical
      ventilation, may prevent secondary pulmonary damage by allowing the use of lower
      ventilator volume-pressure settings.

PMID- 10923735
TI  - Subcutaneous oxygen tensions provide similar information to ileal luminal CO2
      tensions in an animal model of haemorrhagic shock.
AB  - OBJECTIVES: The cutaneous and splanchnic circulations undergo early
      vasoconstriction in shock. Methodological problems and insufficient information
      on subcutaneous carbon dioxide partial pressures limit the usefulness of previous
      studies on splanchnic and subcutaneous gas tensions in shock. Little comparative
      data exist on the responses of these tissues to shock and resuscitation. We
      therefore compared continuous subcutaneous PO2 (PO2sc) and PCO2 (PCO2sc) with
      simultaneous continuous gut luminal PCO2 (PCO2gi) in an animal model of
      haemorrhagic shock and resuscitation. DESIGN: Prospective observational study.
      SETTING: Intensive care laboratory in a teaching hospital. SUBJECTS: Five
      anaesthetised rats. INTERVENTIONS: Electrochemical-fiberoptic gas sensors
      inserted into Silastic tubing placed in the subcutaneous tissue and in the ileal
      lumen measured PCO2sc, PO2sc and PCO2gi continuously in five anaesthetised rats.
      After steady state conditions, hypotension [mean arterial blood pressure (MAP) 40
      mmHg] was induced by controlled haemorrhage. The rats were allowed to remain
      hypotensive for 15 min and then resuscitated with shed blood and crystalloids.
      Arterial plasma lactate concentrations were measured at defined periods during
      the study. MEASUREMENTS AND MAIN RESULTS: Hypovolaemia resulted in a significant
      decrease in PO2sc (P < 0.01) and a significant increase in PCO2gi and PCO2sc (P <
      0.05). These values returned to baseline with resuscitation. PO2sc appeared to
      respond to haemorrhage earlier than PCO2gi and PCO2sc (P = 0.02). PO2sc was
      inversely correlated with PCO2gi (r2 0.7, P < 0.001). There were no significant
      changes in arterial plasma lactate concentrations. CONCLUSIONS: In our rat model,
      subcutaneous oxygen tension provided similar information to ileal luminal PCO2
      and was more rapidly responsive than subcutaneous carbon dioxide tensions and
      arterial lactate during evolving haemorrhagic shock and resuscitation.

PMID- 10923736
TI  - Accuracy and reproducibility of long-term implanted transit-time ultrasound flow
      probes in dogs.
AB  - OBJECTIVE: To assess the accuracy and reproducibility of long-term implanted
      ultrasound transit-time flow probes for measuring cardiac output. DESIGN:
      Prospective animal study. SETTINGS: Animal research laboratory in a university
      department. ANIMALS: Eleven anaesthetised dogs, 24-34 kg. MEASUREMENTS AND
      RESULTS: Flow probes (16-24 mm S-series, Transonic) were implanted around the
      pulmonary artery for a mean duration of 22 months (range 6-47 months).
      Comparisons (n = 147) were made between cardiac output thus obtained and that
      measured by the direct Fick principle using oxygen uptake (Deltatrac II Metabolic
      Monitor) and the arterial to mixed venous oxygen content difference measured by a
      galvanic cell (Lex-O2-Con-TL). Measurements were made either during baseline
      conditions or during pharmacologically altered cardiac output (range 22-180 ml x
      kg(-1) x min(-1)). Regardless of the intervention, the two methods yielded the
      same results in half of the dogs. In the others, however, cardiac output was
      underestimated by the flow probes by up to 38% (probably because of non
      perpendicular position of the probe towards the vessel). This difference was
      constant for the whole range of cardiac output studied and remained constant over
      the entire observation period for each individual dog, so that a correction
      factor was used. Thereafter, the mean difference between the two methods was -1.1
      ml x kg(-1) x min(-1) with a precision (SD) of 14.2 ml x kg(-1) x min(-1) for all
      experiments. CONCLUSIONS: After in vivo calibration, ultrasound transit-time flow
      probes measure cardiac output precisely for several years, regardless of the
      intervention.

PMID- 10923737
TI  - Determination of the clearance factor for transmissible spongiform encephalopathy
      agents during the manufacturing process of polygeline.
AB  - OBJECTIVE: To determine the safety of polygeline, a gelatine-derived plasma
      substitute produced from bovine bones, in terms of safety for bovine spongiform
      encephalopathy (BSE) by evaluating the ability of the manufacturing process of
      polygeline to eliminate agents related to transmissible spongiform encephalopathy
      (TSE) through the validation of three main production steps. DESIGN: Laboratory
      scale experimental process (in duplicate) using 20% hamster-adapted 263K scrapie
      infected brain homogenate as infective titrated source (10(9) LD50/2 ml), added
      to each material before being processed and titrated in hamsters. Experiment 1:
      time/temperature dependency of gelatine autoclaving. Experiment 2: cross-linking
      and distillation. Experiment 3: final sterilization. Monitoring period: 1 year
      with daily animal clinical observation. Histology of all brains. SETTING: LCG-RBM
      laboratories, Italy; strict GLP compliance. MEASUREMENTS AND RESULTS: Heating the
      gelatine (at conditions lower than those used in production process) was very
      effective in inactivating the infectivity of TSE agents. Clearance factors were
      reproducible, dependent upon time and temperature, reaching a total theoretical
      process clearance in the range of 9.2-13.8 [6.9 + 2.3 (+ 4.6)] log10 LD50.
      CONCLUSIONS: These experimental results provide further important data confirming
      the safety of the procedural steps; this complements the safety due to the
      careful sourcing of the raw material. There is high assurance that there is no
      significant risk of TSE transmission to humans by the therapeutic administration
      of polygeline.

PMID- 10923738
TI  - Report from the meeting: Gastrointestinal Tonometry: State of the Art. 22nd-23rd
      May 1998, London, UK.
AB  - Gastrointestinal (GI) tonometry, the only clinically available method for the
      accurate diagnosis of compromised GI blood flow, has been shown to be a sensitive
      predictor of increased morbidity, mortality and prolonged hospitalization. The
      recent introduction of the Tonocap, as a means of performing automated air
      tonometry, has simplified the application of GI tonometry in the clinical
      setting. Despite this the utility of GI tonometry remains controversial. The GI
      Tonometry: State of the Art meeting brought together a group of clinicians with a
      proven track record of research, clinical interest and expertise in this field.
      The aim of the meeting was to come to a consensus regarding certain issues such
      as the past and future roles of GI tonometry and standards for its correct usage
      and interpretation. Finally suggestions as to further research and clinical
      evaluation were made within a broader discussion regarding the complexities of
      applying the principles of evidence-based medicine to the introduction of a new
      piece of medical technology.

PMID- 10923739
TI  - Fulminant Guillain-Barre syndrome mimicking cerebral death: case report and
      literature review.
AB  - A 45-year-old woman was admitted to the intensive care unit (ICU) for respiratory
      arrest. One day prior to admission, she had been nauseated and in a state of
      total exhaustion. On the night of admission she was unresponsive and developed
      gasping respiration. The patient was comatose with absent brainstem reflexes and
      appeared brain dead. Blood chemistry findings and brain magnetic resonance
      imaging were normal. Electroencephalogram revealed an alpha rhythmical activity
      unresponsive to painful or visual stimuli. The cerebrospinal fluid showed an
      albuminocytological dissociation. Guillain-Barre syndrome (GBS) was suspected.
      The electrophysiological evaluation revealed an inexcitability of all nerves. The
      pathological findings of the sural nerve biopsy indicated an axonal degeneration
      secondary to severe demyelination. GBS can very rarely present with coma and
      absent brainstem reflexes. This case illustrates the importance of
      electrophysiological tests and laboratory and imaging studies in patients with
      suspected brain death where a cause is not clearly determined.

PMID- 10923740
TI  - Dialysis disequilibrium syndrome: an unusual cause of respiratory failure in the
      medical intensive care unit.
AB  - We describe a case of the dialysis disequilibrium syndrome (DDS) that was marked
      by the rapid onset of cerebral edema and the subsequent development of acute
      respiratory failure. The patient was treated successfully with a combination of
      mechanical hyperventilation and mannitol. The clinical presentation,
      pathogenesis, prevention and treatment of the entity are discussed.

PMID- 10923741
TI  - Ovarian hyperstimulation syndrome (OHSS): diagnosis and management.
AB  - OBJECTIVE: To present our experience and the current knowledge about
      pathophysiology, diagnosis, and management of the ovarian hyperstimulation
      syndrome (OHSS). DESIGN: Retrospective study concerning clinical and laboratory
      findings of severe OHSS. SETTING: General ICU at a maternity-surgical hospital.
      PATIENTS: Ten patients suffering from severe OHSS. INTERVENTIONS: Supportive and
      preventive therapeutic measures applied are described. MEASUREMENTS AND RESULTS:
      Admission and discharge data as well as worst values during disease course were
      recorded. Clinical and laboratory findings showed third space fluid shift leading
      to weight gain, generalized tissue edema, ascites, hydrothorax, abdominal
      distension and pain, chest discomfort, hypovolemia, dehydration, ovaries
      enlargement, electrolyte disturbances, hypoalbuminemia, high hematocrit, urea,
      and WBC. CONCLUSIONS: OHSS is an iatrogenic complication of assisted conception
      of unknown pathogenesis, with potentially life-threatening sequelae due to
      hemoconcentration such as circulatory shock, ARDS, hepato-renal failure,
      thromboembolic phenomena, and multi-organ dysfunction syndrome. Gynecologists and
      intensivists must be aware of the diagnosis and management of the syndrome
      because of the widely used reproductive techniques for assisted conception.

PMID- 10923742
TI  - Goal-oriented haemodynamic therapy: a plea for a closer look at using peri
      operative oxygen transport optimisation.

PMID- 10923743
TI  - Mechanotransduction, ventilator-induced lung injury and multiple organ
      dysfunction syndrome.

PMID- 10923744
TI  - Intravenous insecticide injection-induced acute respiratory distress syndrome
      successfully treated with steroid therapy.

PMID- 10923745
TI  - Milky-white pleural effusion in a patient with acute respiratory failure: a case
      report.

PMID- 10923746
TI  - Fulminant disease simulating bacterial sepsis with disseminated intravascular
      coagulation after a trip to East Africa.

PMID- 10923747
TI  - Noradrenaline as a vasoactive agent in septic shock.

PMID- 10923748
TI  - Severe cardiogenic shock, after cardioversion, reversed by the intraaortic
      balloon pump.

PMID- 10923749
TI  - Re: Lemaire F (2000) ARDS and PV curves: the inseparable duet. Intensive Care Med
      26: 1-2.

PMID- 10923750
TI  - Zotepine in the prevention of recurrence: a randomised, double-blind, placebo
      controlled study for chronic schizophrenia.
AB  - RATIONALE: Zotepine is an antipsychotic drug with proven efficacy for treatment
      of acute episodes of schizophrenia. Antipsychotic drugs also require to be
      effective in prevention of recurrence. OBJECTIVE: This trial was designed to
      compare the effects of zotepine and placebo in the prevention of recurrence of
      acute episodes in a population of patients with chronic schizophrenia. METHODS:
      The study was a double-blind, parallel group, 26-week comparison of zotepine (300
      mg daily, with fall back to 150 mg if necessary) versus placebo in 121 patients
      with chronic schizophrenia and a history of recurrence in the previous 18 months.
      The primary outcome measure was the time to recurrence. Other evaluations
      included the brief psychiatric rating scale (BPRS), the scale for the assessment
      of negative symptoms (SANS), the clinical global impression (CGI) severity and
      improvement scales, and the Simpson and Angus scale for extrapyramidal symptoms
      (EPS). RESULTS: Fewer zotepine patients experienced recurrence over 26 weeks than
      placebo patients (4 versus 21, respectively). The estimated 26-week risk of
      recurrence was six times lower for zotepine than placebo (8.7% versus 52.8%;
      hazard ratio 0.16, 95% CI 0.053, 0.484; P<0.001). Scores on the BPRS and CGI
      supported the efficacy of zotepine. There was no difference between the
      treatments with respect to EPS. CONCLUSIONS: Zotepine is effective in preventing
      recurrence in patients with chronic schizophrenia. The level of EPS was not
      different between zotepine and placebo.

PMID- 10923751
TI  - The effects of smoking high nicotine cigarettes on prepulse inhibition, startle
      latency, and subjective responses.
AB  - RATIONALE: Several previous investigations with animals and humans have suggested
      that nicotine enhances prepulse inhibition of the startle reflex (PPI). However,
      the administration of nicotine activates mesolimbic dopamine, and activation of
      mesolimbic dopamine is known to attenuate prepulse inhibition of the startle
      reflex (PPI), which might suggest that nicotine would decrease PPI. OBJECTIVE:
      The primary aim of this study was to test rigorously the effects of smoking high
      nicotine cigarettes on PPI and other measures (e.g., heart rate, craving, and
      mood) when the concentration of nicotine peaks in the brain (i.e., immediately
      after smoking). METHODS: Thirty smokers participated in two experimental sessions
      1 week apart. Two high nicotine cigarettes were smoked in one session, and two
      control cigarettes were smoked in the other session after overnight deprivation.
      RESULTS: The results indicated that smoking the high nicotine cigarettes
      decreased PPI and that PPI increased across trials in both conditions. The
      interaction between nicotine dose and trial was not significant, although it
      appeared that high nicotine may have reversed an increase in PPI across trials in
      the control condition. High nicotine cigarettes also significantly increased
      heart rate, decreased the latency to peak startle response on control trials, but
      did not alter the magnitude of the startle response. DISCUSSION: The findings
      suggest that either high nicotine cigarettes reduced PPI, or possibly, that high
      nicotine cigarettes may have reversed an increase in PPI across trials as evident
      in the control condition.

PMID- 10923752
TI  - Opiate withdrawal in the neonatal rat: relationship to duration of treatment and
      naloxone dose.
AB  - RATIONALE: Treatment of developing rat pups with morphine (MOR) causes the
      development of physical dependence, but the relationship of the withdrawal
      syndrome to the duration/intensity of treatment has not been described.
      OBJECTIVES: The purpose of the present study was to characterize the emergence of
      various behavioral components of withdrawal in neonatal rats, and to develop a
      useful measure of overall intensity of withdrawal (OIW). METHODS: Rat pups were
      treated with morphine (MOR) (20 mg/kg, SC, b.i.d.) for 0-5 days. On postnatal day
      10 (P10), animals received saline (SAL) or a challenge dose of MOR (25 mg/kg).
      Withdrawal was precipitated with naloxone HCl (NAL) (0.1, 0.5 or 2.5 mg/kg) 2 h
      after the MOR injection, and behaviors were quantitated for 10 min. To
      investigate the ability of clonidine HCl (CLON) to suppress withdrawal, pups were
      treated for 0 or 5 days with MOR, given a MOR challenge and either SAL or CLON
      (0.2 mg/kg), followed by SAL or NAL (2.5 mg/kg, SC). To evaluate endocrine
      components of withdrawal, growth hormone responses to withdrawal were examined.
      RESULTS: The OIW and NAL-induced GH suppression increased with increasing NAL
      dose and duration of morphine treatment. However, individual behaviors showed
      differing patterns of expression. Clonidine decreased the severity of tremor and
      reduced the OIW. CONCLUSIONS: These results demonstrate that the intensity of
      neonatal opiate withdrawal is related to the duration and intensity of treatment.
      The profile of observed withdrawal behaviors may reflect the involvement of the
      noradrenergic system.

PMID- 10923753
TI  - Decreased mu-opioid receptor binding in the globus pallidus of rats treated with
      chronic haloperidol.
AB  - RATIONALE: Chronic neuroleptic treatment produces a movement disorder in rats
      characterized by vacuous chewing movements (VCMs). Neuroleptics also produce a
      variety of changes in opioid neurotransmission in several regions of the basal
      ganglia. Rats with the VCM syndrome show elevated mRNA for enkephalin in
      striatopallidal neurons, suggesting a possible role for enkephalin in the
      pathophysiology of VCMs. OBJECTIVE: This study investigated the role of mu-opioid
      receptor density in the basal ganglia on the expression of VCMs. METHODS: Rats
      were treated with haloperidol for 24 weeks and withdrawn for 9 weeks. Mu (m)
      receptors were labeled with [3H]-DAMGO. RESULTS: Haloperidol treatment produced a
      significant reduction in mu-receptor binding in the globus pallidus (P<0.05).
      There was, however, no relationship between mu-opioid receptor density and VCMs
      in this or any other region of the basal ganglia. CONCLUSION: These results
      replicate prior findings of a neuroleptic-induced reduction in [3H]-DAMGO binding
      in the globus pallidus. The lack of association between VCMs and [3H]-DAMGO
      binding in the globus pallidus or any other region suggests that prior reports of
      enkephalinergic mRNA changes in the striatum are not accompanied by compensatory
      changes in postsynaptic neurons.

PMID- 10923754
TI  - Associative learning is enhanced by selective neuronal nitric oxide synthase
      inhibitors and retarded by a nitric oxide donor in the rabbit.
AB  - RATIONALE: Previous studies had reported that the nitric oxide (NO) donor, sodium
      nitroprusside (SNP), retarded and the non-specific NO synthase (NOS) inhibitor,
      Nomega-nitro-L-arginine methyl ester (L-NAME), enhanced acquisition of
      classically conditioned responses (CRs). These effects of IV SNP and IP L-NAME on
      CR acquisition occurred in the absence of any effect on non-associative processes
      or performance variables and at a time when there were no alterations in blood
      pressure or heart rate. OBJECTIVES: In this study, we examined whether the
      changes in associative learning produced by L-NAME and SNP were due to their
      central effects on NO content of brain. To this end, we examined the effects of
      the selective neuronal NOS inhibitors 7-nitroindazole (7-NI) and AR-R 17477 and
      the effects of central (ICV) administration of the NO donor SNP on learning.
      METHODS: Effects of drugs on CR acquisition were determined during classical
      conditioning of the rabbit's nictitating membrane (NM) response. Explicitly
      unpaired presentations of conditioned stimuli (CSs) and unconditioned stimuli
      (USs) were employed to measure non-associative levels of responding and
      unconditioned response (UR) topography. RESULTS: The SC injection of 7-NI and AR
      R 17477 significantly enhanced associative learning while ICV administration of
      SNP significantly retarded learning. CONCLUSION: Production of NO within the
      brain by neuronal NOS normally acts to retard associative learning presumably by
      decreasing excitability within neuronal circuits involved in the acquisition of
      the classically conditioned NM reflex.

PMID- 10923755
TI  - A double-blind, placebo-controlled investigation of the efficacy of modafinil for
      sustaining the alertness and performance of aviators: a helicopter simulator
      study.
AB  - RATIONALE: In 1998, the FDA approved modafinil for treating excessive daytime
      sleepiness in narcoleptics, and this has raised questions about the
      appropriateness of this compound for enhancing alertness in sleep-deprived
      controls. This study explored the efficacy of modafinil for maintaining the
      performance of volunteers required to accomplish highly demanding tasks despite
      sleep loss. OBJECTIVE: The principal objective was to determine whether
      prophylactic doses of modafinil would attenuate decrements in aviator performance
      and arousal throughout 2 days and 1 night without sleep. METHODS: Six pilots were
      exposed to two 40-h periods of continuous wakefulness. In one, three 200-mg doses
      of modafinil were given and in the other, matching placebos were administered.
      Helicopter simulator flights, resting EEGs, and Profile of Mood States (POMS)
      questionnaires were evaluated. RESULTS: Modafinil attenuated sleep deprivation
      effects on four of six flight maneuvers, reduced slow-wave EEG activity, and
      lessened self-reported problems with mood and alertness in comparison to placebo.
      The most noticeable benefits occurred between 0330 and 1130 hours, when the
      combined impact of sleep loss and the circadian trough was most severe. The most
      frequently observed drug side effects were vertigo, nausea, and dizziness. These
      could have been related to: 1) the motion-based testing, 2) the use of a
      simulator rather than an actual aircraft (i.e., "simulator sickness"), and/or 3)
      the administration of more than 400 mg modafinil. CONCLUSIONS: Modafinil is a
      promising countermeasure for sleep loss in normals; however, additional studies
      aimed at reducing side effects are needed before it should be used in aviators.

PMID- 10923756
TI  - Appetitive nature of drug cues confirmed with physiological measures in a model
      using pictures of smoking.
AB  - RATIONALE: In smokers, pictures of smoking that increase desire for a cigarette
      are described as pleasant rather than unpleasant. This suggests that these
      smoking cues may be appetitive and not withdrawal-like or aversive as held by
      traditional theories of drug cue formation. OBJECTIVE: Cues for smoking were
      examined using physiological measures of motivational valence. METHODS: Non
      deprived smokers, deprived smokers and deprived smokers who expected to smoke
      (n=54) viewed a computer screen presenting experimental and control scenes
      (experiment 1). The acoustic startle reaction and activity of the corrugator and
      the zygomatic facial muscles were then measured after onset of smoking cues and
      standardized pleasant, neutral or unpleasant control scenes. Individuals who
      never smoked (n=18) were also used to test for cue effects on startle (experiment
      2). RESULTS: No evidence was found that smoking cues were aversive in smokers.
      The smoking cues affected the startle responses and corrugator activity in a way
      similar to that of pleasant control material but significantly different from
      that of unpleasant material; the cue effects on zygomatic activity was most
      similar to that of neutral material. The general pattern of effects was not
      influenced by overnight smoke deprivation, expectancy to smoke or smoke
      repletion, but it was different in never smokers where the smoking scenes were
      found to be similar to unpleasant control scenes. CONCLUSIONS: Nonsubjective
      measures of motivational valence further suggest that drug cues are conditioned
      stimuli having appetitive effects. Startle response modulated by drug cues may be
      useful for probing motivational processes underlying dependence in the human.

PMID- 10923757
TI  - Is benzodiazepine-induced amnesia due to deactivation of the left prefrontal
      cortex?
AB  - The amnesic properties of benzodiazepines result from an impairment in explicit
      (conscious) acquisition of new material. RATIONALE: Explicit encoding of new
      material has consistently resulted in an increase in regional cerebral blood flow
      (rCBF) in the left prefrontal cortex, as measured by positron emission tomography
      (PET). OBJECTIVE: PET was used to determine whether an amnesic dose of midazolam
      (0.075 mg/kg) attenuated activation in this area during explicit memory encoding.
      METHODS: A second condition (condition A) used a task to control for the
      automatic processing that occurs during explicit learning (condition E). RESULTS:
      The subjects who received midazolam (n=7) recognised significantly fewer words
      than those who received placebo (n=8), but were not impaired with regard to
      automatic processing. rCBF was significantly increased in the left prefrontal
      cortex during explicit encoding of word lists in all subjects and in the temporal
      lobe and parieto-occipital regions during automatic processing. rCBF was
      significantly decreased in the prefrontal, superior temporal and parieto
      occipital regions following midazolam. The midazolam-induced deactivation in the
      prefrontal cortex did not affect rCBF activations induced by the explicit memory
      condition (E-A). CONCLUSIONS: These results suggest that a specific interaction
      with prefrontal cortex activation does not underlie the amnesic effect of
      midazolam. However, it remains possible that a threshold level of prefrontal rCBF
      is necessary for encoding and that, after midazolam, this was not reached.

PMID- 10923758
TI  - Anxiety-induced antinociception in mice: effects of systemic and intra-amygdala
      administration of 8-OH-DPAT and midazolam.
AB  - RATIONALE: Mice exhibit antinociception after a single experience in the elevated
      plus maze (EPM), an animal model of anxiety. OBJECTIVE: This study investigated
      the mechanisms involved in this form of anxiety-induced antinociception. METHODS:
      Nociception was evaluated by means of the writhing test in mice confined either
      to the open or enclosed arms of the EPM. The effects of systemic (naloxone,
      midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT, NAN-190 and midazolam)
      drug infusions were investigated in mice previously treated i.p. with 0.6% acetic
      acid, an algic stimulus that induces abdominal contortions. The effects of these
      drugs on conventional measures of anxiety (% entries and % time in open arms) in
      a standard EPM test were also independently investigated. RESULTS: Open-arm
      confinement resulted in a high-magnitude antinociception (minimum 85%, maximum
      450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1
      mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA)
      nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg,
      s.c.) increased OAIA and produced antinociception in enclosed confined animals,
      as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH
      DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response
      at the lowest dose and intensifying it at the highest dose. In addition, low
      doses of this agent reduced anxiety in the EPM. Although bilateral injections of
      8-OH-DPAT (5.6 nmol/0.4 microl) or NAN-190 (5.6 nmol and 10 nmol/0.4 microl) into
      the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In
      contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4
      microl) blocked both OAIA and anxiety. CONCLUSIONS: These results with systemic
      and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the
      amygdala are not involved in the pain inhibitory processes that are "recruited"
      during aversive situations. However, activation of these receptors does
      phasically increase anxiety. Although the intrinsic antinociceptive properties of
      systemically administered midazolam confounded interpretation of its effects on
      OAIA, intra-amygdala injections of this compound suggest that benzodiazepine
      receptors in this brain region modulate both the antinociceptive and behavioural
      (anxiety) responses to the EPM.

PMID- 10923759
TI  - Effects of rolipram on scopolamine-induced impairment of working and reference
      memory in the radial-arm maze tests in rats.
AB  - RATIONALE: Rolipram, a selective inhibitor of cyclic AMP-specific
      phosphodiesterase (PDE4), has been shown to enhance scopolamine-induced
      impairment of working memory. However, its effect on reference memory, which
      appears to be related to the level of cyclic AMP (cAMP), has not been
      investigated yet; in addition, the mechanism involved in its effects on memory
      remains to be elucidated. OBJECTIVES: To investigate the effects of rolipram on
      working and reference memories impaired by scopolamine and the involvement of
      cAMP. METHODS: By administration (IP) of rolipram and forskolin, an activator of
      adenylyl cyclase (AC), the effects of both drugs on the number of correct choices
      and errors in experiment 1 and, the frequency of both working memory errors and
      reference memory errors in experiment 2 were observed in two eight-arm radial
      maze tasks in rats. RESULTS: In experiment 1, rolipram (0.01-1.0 mg/kg)
      attenuated the scopolamine-induced (0.5 mg/kg) increase in the total number of
      errors in dose- and time-dependent manners. The minimum effective dose of
      rolipram was 0.05 mg/kg and the effects lasted nearly 60 min. By contrast,
      forskolin (1.0-10.0 mg/kg) failed significantly to affect any of the above
      indices altered by scopolamine. In experiment 2, rolipram (0.05 and 0.1 mg/kg)
      decreased the frequencies of both working and reference memory errors that were
      elevated by scopolamine. Forskolin did not alter either type of error at a dose
      that increased the exploration time. CONCLUSION: Rolipram may exert its effects
      of reversing both working and reference memory impairments via increased cyclic
      AMP concentrations in certain signal transduction pathways, rather than by a
      generalized increase in cAMP.

PMID- 10923760
TI  - The role of corticotrophin-releasing factor in stress-induced relapse to alcohol
      seeking behavior in rats.
AB  - RATIONALE: Intermittent footshock stress reliably reinstates extinguished alcohol
      taking behavior in drug-free rats, but the neurochemical events involved in this
      effect are not known. OBJECTIVE: We studied here whether two main modulators of
      stress responses, corticotropin-releasing factor (CRF) and corticosterone, are
      involved in reinstatement of alcohol seeking induced by the intermittent
      footshock stressor. METHDOS: Rats were given alcohol in a two-bottle choice
      procedure (water versus alcohol) for 30 days and were then trained for 60 min per
      day to press a lever for alcohol (12% w/v) for 24-30 days in operant conditioning
      chambers. After stable drug-taking behavior was obtained, lever pressing for
      alcohol was extinguished by terminating drug delivery for 5-8 days. Reinstatement
      of alcohol seeking was then determined after exposure to intermittent footshock
      (0.8 mA; 10 min) in different groups of rats that were pretreated with CRF
      receptor antagonists or underwent adrenalectomy (ADX) to remove endogenous
      corticosterone from the body. RESULTS: The CRF receptor antagonists, d-phe-CRF
      (0.3 or 1.0 microg; ICV) and CP-154,526 (15, 30 or 45 mg/kg; IP) attenuated
      footshock-induced reinstatement of alcohol seeking in a dose dependent manner. In
      contrast, the removal of circulating corticosterone by ADX had no effect on
      footshock stress-induced reinstatement of alcohol-taking behavior. In addition,
      the prevention of the footshock-induced rise in corticosterone while maintaining
      basal levels of the hormone by providing adrenalectomized rats with
      corticosterone pellets (50 mg/kg per day), had no effect on stress-induced
      reinstatement. CONCLUSIONS: These data suggest that CRF contributes to stress
      induced relapse to alcohol seeking via its actions on extra-hypothalamic sites.
      The present data, and previous data with heroin- and cocaine-trained rats, point
      to a general role of CRF in relapse to drugs induced by stressors.

PMID- 10923761
TI  - Naltrexone-precipitated morphine withdrawal in infant rat is attenuated by acute
      administration of NOS inhibitors but not NMDA receptor antagonists.
AB  - RATIONALE: There is increasing evidence that the N-methyl-D-aspartate (NMDA)
      receptor and the nitric oxide system are involved in opiate dependence in the
      adult rat, but whether these results in the adult apply to the infant rat is
      unknown. OBJECTIVES: Here we examined the effects of NMDA receptor antagonists
      and nitric oxide synthase (NOS) inhibitors, which reduce the opiate abstinence
      syndrome in adult animals, on morphine withdrawal in the infant rat. METHODS:
      Neonatal rats were injected with morphine sulfate (10.0 mg/kg) twice daily for
      6.5 days. On the 7th day, pups were injected with NOS inhibitors (L-NAME or 7
      NI), NMDA receptor antagonists (MK-801 or AP-5), or vehicle. After 15 min, the
      pups were injected with naltrexone (1 mg/kg) to precipitate withdrawal. Behavior
      for each pup was identified and recorded every 15 s for 10 min before naltrexone
      injection and 15 min after naltrexone injection. RESULTS: Both L-NAME and 7-NI
      significantly reduced most withdrawal behaviors in the infant rat, a result in
      line with previous studies in the adult rat. In contrast, AP-5 reduced some
      withdrawal behaviors but also increased others (e.g., moving paws). MK-801 was
      likewise ineffective in reducing most withdrawal behaviors and increased certain
      withdrawal behaviors (walking and wall climbing). CONCLUSIONS: In the infant rat,
      the production of nitric oxide is involved in opiate withdrawal whereas the NMDA
      receptor may not yet be functionally active or may play only a minor role.

PMID- 10923762
TI  - Stress and relapse to drug seeking in rats: studies on the generality of the
      effect.
AB  - RATIONALE: Intermittent footshock reinstates drug-taking behavior in rats, but
      not behaviors previously maintained by food reinforcers. Here we tested further
      the generality of this phenomenon by determining whether restraint and food
      deprivation stressors would reinstate heroin seeking, whether the environment in
      which footshock is given modulates footshock-induced reinstatement, and whether
      footshock would reinstate operant responding previously maintained by brain
      stimulation reward (BSR). METHODS: Groups of rats were trained to self-administer
      for 10 days either heroin (0.05-0.1 mg/kg/infusion, IV, three 3-h sessions/day)
      or brain stimulation into the septal area (trains of monopolar cathodal pulses of
      100 micros for 500 ms, one 60-min session/day). After extinction of the heroin
      reinforced behavior (10-13 days), the rats were tested for reinstatement after
      exposure to food deprivation (1 and 21 h), restraint given outside the self
      administration environment (5, 15 and 30 min), or intermittent footshock (0.8 mA,
      15 min) given in the self-administration environment or in a novel (non-drug)
      environment. For BSR-trained rats, the effect of footshock on reinstatement after
      extinction (6-10 days) was compared with that induced by noncontingent brain
      stimulation (three or six discrete stimulations at the start of the test
      sessions). RESULTS: Food deprivation reinstated heroin seeking. Footshock
      reliably reinstated heroin seeking when given in the drug environment, but not
      when given in a non-drug environment. Similarly, restraint given outside the self
      administration environment failed to reinstate heroin seeking. In addition,
      footshock was as effective as priming brain stimulation in reinstating operant
      responding previously maintained by BSR. CONCLUSIONS: The effect of footshock on
      reinstatement of heroin seeking generalizes to food deprivation, and appears to
      be dependent on the environment in which the stressor is given. The data with BSR
      indicate that the phenomenon of footshock-induced reinstatement is not selective
      for drug reinforcers.

PMID- 10923763
TI  - Massive increase in serum creatine kinase during olanzapine and quetiapine
      treatment, not during treatment with clozapine.

PMID- 10923764
TI  - Massive serum creatine kinase increases with atypical antipsychotic drugs: what
      is the mechanism and the message?

PMID- 10923765
TI  - The use of antidepressants in patients with advanced cancer.

PMID- 10923766
TI  - A model of palliative care: the palliative medicine program of the Cleveland
      Clinic Foundation. A World Health Organization Demonstrations Project.
AB  - Patients with advanced diseases, both cancer and noncancer, experience high
      symptom prevalence and psychosocial distress. Multiple unmet needs in the
      physical, psychosocial and spiritual domains are common. In the United States,
      palliative medicine is an emerging discipline that focuses on meeting these needs
      to achieve optimal quality of life for the patient-family unit. The majority of
      palliative care programs in the U.S. are consultation based. In contrast, the
      Palliative Medicine Program of the Cleveland Clinic Foundation offers
      multidisciplinary, comprehensive care from a primary or a consultative focus. The
      program has clinical, research, and educational components. Established as a
      consultation service in 1987, the clinical component now includes inpatient and
      outpatient consultation services, a dedicated acute care inpatient hospital unit,
      outpatient palliative medicine and cancer pain clinics, palliative home care,
      hospice home care and hospice residential care. Over 800 new patient
      consultations took place in 1997. In this paper, development of the program and
      its structure are described. Challenges to effective communication in a large
      program within a tertiary care institution are discussed, and strategies designed
      to meet these challenges are presented.

PMID- 10923767
TI  - Psychopharmacology in supportive care of cancer: a review for the clinician. III.
      Antidepressants.
AB  - This review covers pharmacokinetics, adverse effects and drug interactions of
      antidepressants and the indications for them, with the aim of assisting the
      clinician working in palliative and supportive care in the prescription of such
      drugs. Practical considerations and decision trees to be used prior to the
      prescription of an antidepressant are also part of this review. Special emphasis
      is put on the management of depression, which is frequent in patients with
      advanced cancer and often remains underdetected and undertreated, or is treated
      at a stage when there is little time for medication to have an effect.

PMID- 10923768
TI  - New tools in diagnosing catheter-related infections.
AB  - Clinical criteria alone are insufficient to allow a diagnosis of intravascular
      catheter-related sepsis (CRS). A definite diagnosis of CRS usually requires
      removal of the catheter for quantitative catheter tip culture. However, only
      about 15-25% of central venous catheters (CVC) removed because infection is
      suspected actually prove to be infected, and the diagnosis is always
      retrospective. Other diagnostic tests, such as differential quantitative blood
      cultures from samples taken simultaneously from the catheter and a peripheral
      vein, have been proposed to avoid unjustified removal of the catheter and the
      potential risks associated with the placement of a new catheter at a new site: a
      central-to-peripheral blood culture colony count ratio of 5:1 to 10:1 is
      considered indicative of CRS. Despite its high specificity, the latter diagnostic
      technique is not routinely used in clinical practice because of its complexity
      and cost. The measurement of the differential time to positivity between hub
      blood (taken from the catheter port) and peripheral blood cultures might be a
      reliable tool facilitating the diagnosis of CRS in situ. In an in vitro study, we
      found a strong relationship between the inoculum size of various microorganisms
      and the time to positivity of cultures. When the times to positivity of cultures
      of blood taken simultaneously from central and peripheral veins in patients with
      and without CRS were examined, we found that earlier positivity of central vs
      peripheral vein blood cultures was highly correlated with CRS. Using a cut-off
      value of +120 min, the "differential time to positivity" of the paired blood
      samples, defined as time to positivity of the peripheral blood minus that of the
      hub blood culture, had 91% specificity and 94% sensitivity for the diagnosis of
      CRS. This method may be coupled with other techniques that have high negative
      predictive value, such as skin cultures at the catheter exit site. This
      diagnostic test can be proposed for routine clinical practice in most hospitals
      using automatic devices for blood cultures positivity detection. Endoluminal
      brushing of the catheter is considered sensitive and specific for the diagnosis
      of CRS, but the risk of embolisation or subsequent bacteraemia should be
      considered. Gram staining and the acridine-orange leucocyte cytospin test on
      through-catheter blood culture have been proposed for rapid diagnosis of CRS
      without catheter removal. The technique, which requires 100 microl catheter blood
      and the use of light and ultraviolet microscopy, is considered simple, rapid (30
      min) and inexpensive. In conclusion, diagnostic tools such as paired blood
      cultures or Gram staining and the acridine-orange leucocyte cytospin test should
      allow a diagnosis of CRS without catheter removal in cancer patients.

PMID- 10923769
TI  - Ceftriaxone versus beta-lactams with antipseudomonal activity for empirical,
      combined antibiotic therapy in febrile neutropenia: a meta-analysis.
AB  - The object of this work was to compare the efficacy of antibiotic combinations
      including ceftriaxone with that of combinations including an antipseudomonal beta
      lactam for the empirical treatment of febrile neutropenia in cancer patients. We
      identified all published randomised trials comparing two antibiotic combinations
      differing only in the beta-lactam, being ceftriaxone in one treatment group and
      an antipseudomonal beta-lactam in the other. The quality of individual trials was
      formally evaluated. A meta-analysis was performed using the Peto-modified Mantel
      Haenszel method for combining binary data. Primary analysis was done, for both
      febrile episodes and bacteraemic episodes, using failure of empirical antibiotic
      treatment defined as modification of the initial allocated regimen or death
      during treatment. Secondary analysis was done using death from any cause in the
      two treatment groups. Data relating to 1,537 febrile neutropenic episodes
      recorded in eight randomised clinical trial were pooled s. Overall, there were
      256 treatment failures out of 782 febrile episodes treated with ceftriaxone
      containing combinations (32.7%), and 243 out of 755 treated with antipseudomonal
      beta-lactam regimens (32.1%). The pooled odds ratio of failure for ceftriaxone
      containing combinations for febrile episodes was 1.04, with the 95% confidence
      interval ranging from 0.84 to 1.29, and that for bacteraemic episodes was 0.93
      (95% confidence interval 0.58-1.49). With regard to overall mortality, there were
      54 deaths among 782 febrile episodes treated with ceftriaxone-containing
      combinations (6.9%) and 62 deaths among 755 febrile episodes treated with
      antipseudomonal beta-lactam-containing regimens (8.2%). The pooled odds ratio of
      death for ceftriaxone regimens was 0.84 (95% confidence interval 0.57-1.24).
      Results of this meta-analysis show that in the empirical treatment of febrile
      neutropenia, antibiotic combinations containing ceftriaxone are as effective as
      those in which the beta-lactam has specific activity against Pseudomonas
      aeruginosa, such as ureidopenicillin or ceftazidime.

PMID- 10923770
TI  - Characteristics of deaths in a department of oncohaematology within a general
      hospital. A study of 81 cases.
AB  - We aimed to perform a prospective analysis of the main characteristics of deaths
      occurring in the oncohaematology department of a general hospital. From November
      1995 to February 1997, a total of 81 patients died in our unit, 50 of whom
      (61.7%) were male. Their mean age was 67.8 (range 19-96) years. Underlying
      diseases were: multiple myeloma (9 cases), acute myeloid leukaemia (22), lymphoma
      (14), chronic lymphocytic leukaemia (6), acute lymphoblastic leukaemia (4),
      myelodysplastic syndromes (3), solid tumours (11), and other (12). The previous
      disease duration ranged from 5 days to 276 months (mean 31.9 months). The
      duration of the last hospital stay varied between 0 (death on arrival or on way
      to hospital) and 40 days (mean 9.3 days). Two patients died in the emergency unit
      just before entering our department (1 suicide). Only 15 patients had been
      admitted for the first time. In 70% of these cases death appeared predictable, as
      the consequence of refractory or end-stage disease. In these cases, all the "do
      not resuscitate" orders were in place at least 48 h before death. About half the
      patients died without any relative present. The frequencies of the clinical
      complaints evaluated were the following: pain necessitating opiates 27%;
      infection- or disease-related fever 40%; dyspnoea 44%; haemorrhage 20%; CNS
      disturbances 25%. The percentages of use of therapy tools chosen as indicators
      were: benzodiazepines 80%; chemotherapy 46%; anti-infectious agents 47%;
      transfusions 42%; major analgesics 27%; and steroids 40%. The circumstances and
      quality of patient deaths must be regularly evaluated so that palliative care in
      the final stages of life can be improved.

PMID- 10923771
TI  - The impact of home palliative care on symptoms in advanced cancer patients.
AB  - Physical symptoms, which are highly prevalent in patients with cancer, have a
      major impact on many aspects of quality of life, and the best possible quality of
      life is the principal aim of palliative care. Few studies have reported the
      impact of home care on pain and symptoms among cancer patients living at home.
      The aim of this study was to evaluate the impact of home palliative care given by
      an experienced team on symptoms in advanced cancer patients. A consecutive series
      of 373 patients who were referred to a home palliative care program in the period
      1993-1995 were prospectively evaluated. Patients were enrolled for the presence
      of different symptoms (pain, nausea and vomiting, dry mouth, dysphagia, gastric
      discomfort, constipation, diarrhea, dyspnea, drowsiness, weakness, confusion,
      psychological symptoms). For the purpose of the study we have selected 211
      patients who, according to a retrospective assessment, survived for longer than 3
      weeks and who were followed up until their deaths. Pain, nausea and vomiting,
      gastric discomfort, and diarrhea significantly decreased after palliative
      intervention. This improvement was maintained until death, whereas, after an
      initial improvement, dyspnea and constipation tended to increase in intensity in
      the last days of life. Drowsiness, weakness, and confusion increased in intensity
      in the last days of patients' lives. Similarly, fluid and food intake
      significantly decreased during the last days of life. Opioid dosage and frequency
      of opioid use increased with time, but this change did not reach statistical
      significance until the last days, when 70% of patients were taking opioids. These
      figures demonstrate the good impact of palliative care in this group of patients.

PMID- 10923772
TI  - Prevalence and severity of symptoms in terminal cancer patients: a study in
      Taiwan.
AB  - This paper reports a prospective study conducted between September 1997 and July
      1998 in 232 consecutive patients with terminal cancer. A structured data
      collection form was used daily to evaluate symptoms, which were analyzed at the
      time of admission, 1 week after admission and 48 h before death. Terminal cancer
      patients in this study were polysymptomatic. There were no statistically
      significant differences in the prevalence of most symptoms with the primary site
      of cancer. The majority of symptoms improved at the end of the 1st week after
      admission, but many symptoms worsened just before death. The high prevalence of
      symptoms and lack of significant difference among primary tumor sites may be
      related to shorter survival times caused by late referral, which is common in
      Taiwan.

PMID- 10923773
TI  - Use of and attitudes held towards unconventional medicine by patients in a
      department of internal medicine/oncology and haematology.
AB  - A sizeable percentage of patients receiving conventional medical treatment also
      use unconventional medicine (UM). Surveys indicate that the prevalence of and
      motivation for the pursuit of the different approaches of UM is subject to
      individual, geographical, cultural and disease-related factors. We were
      interested in the concurrent use of and attitudes towards UM in patients who
      underwent conventional medical treatment in our oncologically orientated
      department of internal medicine in a regionally dominant teaching hospital. A
      representative sample (n = 131) of all inpatients and outpatients receiving
      treatment in the department or in its oncological/haematological outpatient
      clinic were asked to participate in a cross-sectional interview study on the use
      of unconventional therapies. In all, 128 patients (97.7%) agreed to participate
      in the study, and 65% of these patients were suffering from malignancies. Use of
      unconventional treatment was reported by 24% of all patients for their current
      medical problem, and 16% of the remaining patients had been thinking of
      adjunctive use. The use of UM was significantly higher among oncological patients
      (32%), and among oncological outpatients in particular (50%), than among patients
      with acute or chronic non-malignant diseases. Female patients predominated among
      the users of UM (71%). UM mainly took the form of various pharmacological and
      dietary approaches. Patients availing themselves of UM most frequently identified
      physicians (41%) as the source of treatment recommendation. Only 18% of the users
      of UM relied on these methods as a chance of cure. Use of UM was not generally
      motivated by dissatisfaction with conventional medical care. Only half the users
      informed their hospital physician of their adjunctive use of UM. Nearly 2 out of
      3 of the users contended that UM had contributed to a mild or distinct
      improvement in their physical or psychological wellbeing. The use of UM in modern
      health care systems represents a widespread and intricate phenomenon, which
      cannot be understood by focusing exclusively on the objective assessment of
      clinical efficacy. Use of UM may be related more to a disease's unfavourable
      attribution than to its medically expected outcome. Coherence with individual
      illness paradigms and perceived efficacy are apparently important factors in
      patients' use of UM. These subjective aspects need to be recognised in caring
      patient-doctor communication.

PMID- 10923774
TI  - Randomised double blind crossover study comparing ondansetron, granisetron and
      tropisetron. A cost-benefit analysis.
AB  - The goals of this work were to compare the relative efficacy of ondansetron,
      granisetron and tropisetron in a randomised double blind crossover trial,
      evaluating objective, subjective and pharmacoeconomic parameters. To this end,
      136 patients were enrolled, 120 of whom were eligible and evaluable. Each patient
      received three identical chemotherapy cycles with an antiemetic protocol which
      consisted in dexamethasone 20 mg i.v. and a tapering dose schedule for 4 days,
      and a single i.v. dose of an antiserotoninergic drug in each cycle. Arm A
      patients received tropisetron 5 mg; arm B patients, granisetron 3 mg; and arm C
      patients, ondansetron 24 mg. Numbers of patients and days with emetic episodes,
      grade of nausea, patient preference, headaches, need for metoclopramide, nursing
      or medical consultation, or admission to emergency room or ward were evaluated.
      There was no difference in the percentage incidence of acute or delayed nausea
      and vomiting. Twenty-five per cent of patients preferred tropisetron, 30%
      preferred granisetron, and 45% preferred ondansetron (P<0.01). Toxicity was mild
      in less than 10% of patients. Direct and indirect costs of treatment varied from
      19.74 to 28.53 euros for tropisetron, 31.07-46.51 euros for granisetron and 22.76
      62.61 euros for ondansetron. There was no difference in objective activity. In
      the schedules studied, patients preferred ondansetron. Indirect costs amount to
      less than 10% of the total antiemetic cost. Direct costs varied widely and should
      be considered whenever an antiemetic drug is selected.

PMID- 10923775
TI  - Treatment of catheter-induced thrombotic superior vena cava syndrome: a single
      institution's experience.
AB  - Thrombosis is the most frequent benign etiology of superior vena cava syndrome
      among cancer patients who have a long-term central venous catheter. In this
      paper, six cases of thrombotic superior vena cava syndrome are discussed. There
      were four women and two men. One patient was treated with streptokinase and five
      with urokinase. The mean age was 46 years (range 22-69), and the mean time for
      thrombosis development after catheter insertion was 125 days (range: 53-211
      days). The mean time for resolution of thrombosis was 7 days (range 2-11) in five
      patients. One patient had no response to fibrinolysis.

PMID- 10923776
TI  - A manic episode associated with bereavement in a patient with lung cancer. A case
      report.
AB  - We describe a manic episode associated with bereavement in a lung cancer patient.
      The patient became manic 4 days after the death of a close friend also suffering
      from lung cancer, though the deceased was not a member of his immediate family.
      Manic episodes in cancer patients are rare, and our report of a manic episode
      associated with bereavement may also serve to highlight possible precipitating
      factors, which have not been adequately emphasized in the literature to date.

PMID- 10923777
TI  - Bioelectrical impedance, cancer nutritional assessment, and ascites.
AB  - This report describes our experience in the use of bioelectrical impedance
      analysis (BIA) as a method of nutritional assessment in a cancer patient with
      ascites. The BIA was an unreliable measure of body composition in this setting.

PMID- 10923778
TI  - Superiority of dietary safflower oil over olive oil in lowering serum cholesterol
      and increasing hepatic mRnas for the LDL receptor and cholesterol 7alpha
      hydroxylase in exogenously hypercholesterolemic (exHC) rats.
AB  - The exogenously hypercholesterolemic (ExHC) rat is a strain segregated from SD
      rats with a high response to dietary cholesterol. To understand the underlying
      mechanism(s) for this hypercholesterolemia, the interactive effects of dietary
      fatty acid and the susceptibility of rats to dietary cholesterol on the serum
      cholesterol concentration and hepatic mRNA abundance of the low-density
      lipoprotein (LDL) receptor, cholesterol 7alpha-hydroxylase (7alpha-hydroxylase)
      and 3-hydroxyl-3methylglutaryl (HMG) CoA reductase were examined. Both strains
      were fed on a diet supplemented with 10% each of olive, safflower or coconut oil
      with or without the addition of 1% cholesterol for one week. The ExHC rats fed on
      olive, safflower and coconut oil in combination with cholesterol respectively
      resulted in a 3.5-, 2.0- and 2.1-fold higher serum cholesterol concentration than
      that in the animals fed on the corresponding dietary fats without any
      supplementation of cholesterol (p < 0.01 by dietary cholesterol or type of fat).
      The dietary cholesterol dependent-elevation of serum cholesterol in the SD rats
      was less than 1.5-fold (p<0.01) and there was no dietary fat effect. The ExHC
      rats fed on the safflower oil-containing diet supplemented with cholesterol
      resulted in a higher mRNA abundance of the LDL receptor and 7alpha-hydroxylase
      than in the corresponding fat-fed rats without cholesterol (p<0.05). There was no
      dietary cholesterol-dependent change of mRNA abundance in either strain fed on
      olive or coconut oil, except for a decreased abundance of HMG CoA reductase mRNA
      in the olive oil-fed ExHC rats and coconut oil-fed Sprague-Dawley (SD) rats
      (p<0.05). These results indicate that the hepatic mRNA abundance of the LDL
      receptor and of 7alpha-hydroxylase depended on the dietary combination of
      cholesterol and a fatty acid and suggest that a linoleic acid-rich diet may
      alleviate exogenous hypercholesterolemia by activating the process involved in
      the hepatic uptake and biliary excretion of serum cholesterol.

PMID- 10923779
TI  - HPLC analysis of white lupin isoflavonoids.
AB  - An investigation of the HPLC analytical conditions for simple isoflavones,
      prenylated isoflavones and some of their glucosyl derivatives resulted in
      reasonable separation and total elution in 35 min when using a reversed-phase C18
      Lichrospher column and a gradient elution system of MeCN-THF-H2O. This method was
      successfully applied to quantify the changes in isoflavonoid constituents in
      white lupin (Lupinus albus L.) tissues: (a) young legumes (pods and seeds) during
      maturation, and (b) soaked, germinating seeds. In developing legumes, genistein
      and 2'-hydroxygenistein, as well as their prenylated derivatives, were present in
      the pods as the major components, together with minor amounts of glucosides,
      whereas only minute amounts of isoflavonoids were detectable in the ripening
      seeds. When soaked with water, mature lupin seeds which normally contain trace
      amounts of isoflavonoids, started rapidly to biosynthesize simple isoflavones and
      accumulate large amounts of genistein 7-O-glucoside and its 6"-O-malonyl
      derivative. These dynamic changes are discussed in relation to the role of
      isoflavonoids in the lupin defense system.

PMID- 10923780
TI  - Binding affinity of T7 RNA polymerase to its promoter in the supercoiled and
      linearized DNA templates.
AB  - A promoter competition assay was used to measure the stability of T7 RNA
      polymerase with its promoter. When T7 RNA polymerase was incubated with GTP for 5
      minutes before the elongation of transcription in either the supercoiled or
      linearized template, the half-lives of T7 RNA polymerase-DNA complexes were
      reduced. The transcription product increased when T7 RNA polymerase preincubated
      with GTP in the supercoiled DNA but not in the linearized DNA template. On the
      other hand, preincubation of ATP with T7 RNA polymerase decreased the stability
      of T7 RNA polymerase with the supercoiled DNA, but did not affect the stability
      of T7 RNA polymerase with the linearized DNA. Furthermore, the production of RNA
      transcript was increased when T7 RNA polymerase was incubated with ATP in either
      supercoiled or linearized template before transcription elongation. This study is
      important to understand the relationship between the transcription initiation and
      the stability of the ternary complex, and to produce large quantities of RNA
      transcript in vitro.

PMID- 10923781
TI  - A new high-alkaline and high-molecular-weight pectate lyase from a Bacillus
      isolate: enzymatic properties and cloning of the gene for the enzyme.
AB  - A pectate lyase (Pel; pectate transeliminase: EC4.2.2.2.), designated Pel-15H,
      was found in an alkaline culture of Bacillus sp. strain KSM-P15 and purified to
      homogeneity by sequential column chromatographies. The molecular weight of the
      enzyme determined by SDS-polyacrylamide gel electrophoresis was approximately
      70,000 and the pI was around pH 4.6. Pel-15H randomly trans-eliminated
      polygalacturonate in the presence of Ca2+ ions, and the maximum activity was
      observed at pH 11.5 and at 55 degrees C in glycine-NaOH buffer. The gene for Pel
      15H was cloned and sequenced, and the structural gene contained a 2,031-bp open
      reading frame that encoded 677 amino acids including a possible 28-amino-acid
      signal sequence. The mature enzyme (649 amino acids, molecular weight 69,550)
      showed very low similarity to Pels from Bacillus with 12.7-18.2% identity.
      Interestingly, part of the amino acid sequence of Pel-15H had fairly high
      similarity only to an N-terminal half of PelL and a C-terminal half of PeIX from
      Erwinia chrysanthemi 3937, and a C-terminal half of PeIX from E. chrysanthemi
      EC16 (approximately 35% identity for all).

PMID- 10923782
TI  - Apoptosis induced by niacin-related compounds in K562 cells but not in normal
      human lymphocytes.
AB  - In our previous study, we found that niacin-related compounds induced apoptosis
      in human acute myelomonocytic leukemia cells, HL-60. We have investigated whether
      these compounds acted as inducers of apoptosis also in various other cell types.
      In human chronic myelogenous leukemia cells, K562, which are relatively resistant
      to various inducers of apoptosis, the apoptosis was induced by picolinic acid and
      dipicolinic acid in about 50% of the cells 5-10 mM via the caspase pathway, but
      was not at 1 mM. However, isonicotinamide did not induce apoptosis effectively in
      K562 cells. On the other hand, in normal human quiescent lymphocytes, the
      apoptosis was not induced by these compounds at the same concentrations. It is
      suggested that these compounds may induce apoptosis mainly in tumor cells. The
      change of intracellular peroxide levels was observed in the early phase of
      apoptosis induced by niacin-related compounds. We expect to make use of niacin
      related compounds in the field of medicine.

PMID- 10923783
TI  - Crystal transformation from anhydrous alpha-maltose to hydrous beta-maltose and
      from anhydrous trehalose to hydrous trehalose.
AB  - Anhydrous sugars such as maltose and trehalose are useful for making dry powder
      of foods and liquids. The crystal-transformation rate of maltose and trehalose
      were investigated under humid conditions and by kneading. The enthalpy for
      solubilization was 7.0 kJ/mol for the anhydrous maltose. The crystal
      transformation rate of anhydrous alpha-maltose to hydrous beta-maltose depended
      on the temperature at 75% humidity. However, that of anhydrous trehalose did not
      depend on the temperature, and transformation was very rapid. An anomeric change
      to maltose and no such change to trehalose might have caused this. The activation
      energy of crystal transformation was 79 kJ/mol for maltose and zero for
      trehalose. The rate of crystal transformation of anhydrous maltose while kneading
      depended on the purity of the anhydrous alpha-maltose and the amount of water
      present. This crystal transformation rate fitted the Avrami equation.

PMID- 10923784
TI  - Protection against the diabetogenic effect of feeding tert-butylhydroquinone to
      rats prior to the administration of streptozotocin.
AB  - We determined whether an oral administration of the synthetic antioxidant, tert
      butylhydroquinone (TBHQ), or the naturally occurring lipoxygenase inhibitor,
      curcumin, to rats would provide protection against the diabetogenic effect of
      streptozotocin (STZ). Male Sprague-Dawley rats were fed on an AIN-76-based
      purified diet containing 0.0028% TBHQ or on the purified diet with a daily
      intragastric administration of curcumin (200 mg/kg of body weight) for one week
      while receiving intravenously administered STZ. The rats fed on the TBHQ
      containing diet were resistant to diabetes development when compared with the
      rats fed on the TBHQ-free diet and had a higher body weight gain and lower serum
      glucose concentration. Glucose-stimulated insulin secretion from the pancreatic
      islet in the rats that had received TBHQ was higher than that in the control
      rats. The rats receiving curcumin showed no beneficial effect on these diabetic
      symptoms. These findings provide direct evidence for the suggestion that dietary
      supplementation of an antioxidant may exert a preventive effect on the
      diabetogenic action of free-radical producers.

PMID- 10923785
TI  - Refolding of denatured/reduced lysozyme at high concentration with diafiltration.
AB  - Refolding of reduced and denatured protein in vitro has been an important issue
      for both basic research and applied biotechnology. Refolding at low protein
      concentration requires large volumes of refolding buffer. Among various refolding
      methods, diafiltration is very useful to control the denaturant and red/ox
      reagents in a refolding solution. We constructed a refolding procedure of high
      lysozyme concentration (0.5-10 mg/ml) based on the linear reduction of the urea
      concentration during diafiltration under oxygen pressure. When the urea
      concentration in the refolding vessel was decreased from 4 M with a rate of 0.167
      M/h, the refolding yields were 85% and 63% at protein concentrations, 5 mg/ml and
      10 mg/ml, respectively, after 11 h. This method gave a high productivity of
      40.1,microM/h of the refolding lysozyme. The change in refolding yields during
      the diafiltration could be simulated using the model of Hevehan and Clark.

PMID- 10923786
TI  - Identification of a taurine transport inhibitory substance in sesame seeds.
AB  - An ethanol extract from sesame seeds inhibited the taurine uptake in human
      intestinal epithelial Caco-2 cells. The uptake of such alpha-amino acids as
      leucine and glutamic acid was not inhibited by the extract, indicating that this
      inhibition is specific to the taurine uptake. The unknown inhibitor in the sesame
      extract was purifled by reversed-phase HPLC by monitoring the inhibitory effect
      on taurine uptake. The isolated substance was identified as
      lysophosphatidylcholine, linoleoyl (Lyso-PC), by NMR and MS analysis. Lyso-PC
      inhibited the taurine uptake in a dose-dependent manner with an IC50 value of
      approximately 200 microM. Although Lyso-PC is known to be a surface active and
      cell lytic compound, neither damage nor loss of integrity of the Caco2 cell
      monolayer was apparent after treating with 200 microM Lyso-PC. Inhibition was
      observed by incubating cells with Lyso-PC for only 1 min prior to the uptake
      experiments. These results suggest the direct effect of Lyso-PC on the cell
      membrane to be the main mechanism for this inhibition. Lyso-PC may play a role in
      the regulation of certain intestinal transporters.

PMID- 10923787
TI  - Purification, characterization and substrate specificities of xylanase isoenzymes
      from Melanocarpus albomyces IIS 68.
AB  - The ascomycetous fungus Melanocarpus albomyces when grown on wheat straw produced
      seven extracellular xylanase isoenzymes, designated as la, Ib, Ic, IIa, lib, llc,
      and lId. All seven xylanases were purified to homogeneity by gel filtration and
      ion-exchange chromatography. The molecular mass (kDa) of la, lb, Ic, Ila, lIb,
      lIc, and lId were estimated to be 22.9, 20.7, 18.6, 31.3, 25.4, 38.5, and 34.3,
      respectively by SDS-PAGE, and 23.7, 20.5, 17.1, 31.7, 25.1, 39.8, and 32.2,
      respectively by gel filtration. The isoelectric points of Ia, lb, Ic, Ila and IIb
      were found to be 6.2, 6.3, 6.4, 3.7, and 4.4, respectively. The activity of the
      isoenzymes was dependent on the type of the xylan substrates; Xylanases Ia, lb,
      and Ic showed highest specific activity toward larchwood xylan (an
      arabinoglucuronoxylan), IIa and Ilc toward birchwood xylan (a glucuronoxylan),
      and llb and IId toward beechwood xylan (a glucuronoxylan). Four isoenzymes la,
      lb, Ic, and Ila had an arabinose-releasing property on larchwood xylan.
      Application of specific isoenzymes as prebleaching agents in paper manufacture is
      proposed.

PMID- 10923788
TI  - Purification and characterization of a novel alpha-L-arabinofuranosidase from
      Pichia capsulata X91.
AB  - An intracellular alpha-L-arabinofuranosidase from Pichia capsulata X91 was
      purified and characterized. The enzyme was purified to homogeneity from a cell
      free extract by ammonium sulfate treatment, Concanavalin A-Sepharose, ion
      exchange chromatography with DEAE Bio-Gel A agarose, arabinose-Sepharose 6B
      affinity chromatography, and hydroxyapatite column chromatography. The apparent
      molecular mass of the enzyme was estimated to be 250 kDa by native-PAGE. The
      enzyme molecule was suggested to be a tetramer with a subunit molecular mass of
      72 kDa by SDS-PAGE. The enzyme had an isoelectric point at 5.1, and was most
      active at pH 6.0 and at around 50 degrees C. The alpha-L-arabinofuranosidase was
      active at ethanol concentrations of wine. The enzyme was inhibited by Cu2+, Hg2+,
      and p-chloromercuribenzoate. The enzyme hydrolyzed beet arabinan and
      arabinogalactan, and efficiently released monoterpenols from an aroma precursor
      extracted from Muscat grape juice. A considerable amount of monoterpenols was
      produced in the Muscat wine coupled with the enzyme addition.

PMID- 10923789
TI  - Fatty acid hydroperoxide lyase in tomato fruits: cloning and properties of a
      recombinant enzyme expressed in Escherichia coli.
AB  - Fatty acid hydroperoxide lyase (HPL) is a member of a novel subfamily of
      cytochrome P450 and catalyzes a cleavage reaction of fatty acid hydroperoxides to
      form short-chain aldehydes and oxo-acids. A cDNA encoding tomato fruit HPL
      (LeHPL) was obtained. An active LeHPL was expressed in E. coli and purified. It
      showed highest activity against the 13-hydroperoxide of linolenic acid, followed
      by that of linoleic acid. 9-Hydroperoxides were poor substrates. The absorption
      spectrum of the purified LeHPL in the native form was similar to that of most
      P450s although a CO-adduct having a lambda max at 450 nm could not be obtained.
      LeHPL activity is reversibly inhibited by nordihydroguaiaretic acid, while
      salicylic acid irreversibly inhibited it. LeHPL is kinetically inactivated by
      fatty acid hydroperoxides, especially 9-hydroperoxides. The inactivation is
      prevented by inhibitors of LeHPL. Thus, HPL catalytic activity is thought to be
      essential to its inactivation. During the inactivation, an abolition of the Soret
      band was evident, indicating that inactivation is caused mainly by degradation of
      the prosthetic heme in LeHPL.

PMID- 10923790
TI  - Expression of prophenoloxidase mRNA during silkworm hemocyte development.
AB  - Two clones encoding different prophenoloxidase isoforms were amplified by
      polymerase chain reaction of RNA from the hemocytes of an experimental strain of
      Bombyx mori. The nucleotide sequences of the clones and the deduced amino acid
      sequences were confirmed to be nearly identical to those of the orthologous
      clones previously obtained from a commercial race of B. mori. Northern blot
      hybridization using these clones as probes demonstrated that the prophenoloxidase
      mRNA in the hemocytes is expressed in a stage-specific manner during the final
      larval instar and pupal stage, showing a peak one day before pupation in males
      and on the day of pupation in females. A sexual difference was also observed when
      the content of prophenoloxidase protein in the hemolymph (including hemocytes)
      was measured by an enzyme-linked immunosorbent assay.

PMID- 10923792
TI  - Molecular cloning, overproduction and characterization of the Bacillus cereus IMP
      dehydrogenase.
AB  - The gene of IMP dehydrogenase of Bacillus cereus ts-4, a temperature-sensitive
      mutant of B. cereus JCM 2152, was subcloned and its sequence was analyzed. A B.
      cereus ts-4 DNA fragment of 2,065 bp containing the entire impdh gene and
      flanking regions was sequenced. The fragment contained an open reading frame of
      1,527 bp encoding 509 amino acids with a calculated molecular mass of 55,390 Da.
      The impdh sequence of JCM 2152 was also analyzed by TA cloning using PCR products
      amplified with primers from B. cereus ts-4 impdh gene. The gene amplified by PCR
      was expressed in Escherichia coli using a pET17 x b expression plasmid. The N
      terminal amino acid sequence of the overproduced enzyme was identified as Met-Trp
      Glu-Ser-Lys-Phe-Val-Lys-Glu-Gly-Leu-Thr-Phe-AspAsp-Val-Leu -Leu-Val- Pro. The
      overproduced enzyme was eluted at a molecular mass of about 225 kDa by gel
      filtration. The molecular mass of the subunit was estimated to be 56 kDa by SDS
      PAGE. The overproduced enzyme was active against IMP, IDP, and ITP, and showed
      the highest activity at pH 9.5. These properties of the recombinant enzyme were
      almost identical to those of IMP dehydrogenase of B. cereus.

PMID- 10923791
TI  - Transcription of emrKY is regulated by the EvgA-EvgS two-component system in
      Escherichia coli K-12.
AB  - Spontaneous mutations have been isolated in Escherichia coli that result in the
      constitutive expression of an emrKY promoter. These mutations were found to be
      single-nucleotide substitutions within the linker region of the sensor protein
      EvgS, which is part of a two-component regulatory system along with EvgA. In the
      linker mutants (evgSI and evgS4), emrKY expression became constitutive and MIC
      against sodium deoxycholate was 20 mg/ml, eight-fold higher than in the wild
      type. Furthermore, the start site of transcription from the promoter of emrKY was
      identified; EvgA was shown to bind at the -52 to -84 region by the footprinting
      experiment.

PMID- 10923793
TI  - Molecular cloning and sequence analysis of a gene encoding an extracellular
      proteinase from Lactobacillus helveticus CP790.
AB  - A 2.6-kilobase HaeIII DNA fragment corresponding to an extracellular proteinase
      gene (prtY) was cloned from chromosomal DNA of Lactobacillus helveticus CP790 in
      Escherichia coli using a pKK223-3 vector. The transformant expressed a 48-kDa
      protein that reacts with monoclonal antibodies specific to the proteinase and
      seemed to be a pre-proproteinase, but had no proteolytic activity. About 1.6
      kilobases of the 2.6-kilobase DNA fragment, which contained the complete gene for
      the proteinase was sequenced. Sequence analysis found an open reading frame with
      a capacity to encode a protein of 449 amino acids. The coding region contained a
      Gram-positive-type signal peptide of 30 amino acids. The N-terminal sequences of
      the proproteinase and the mature proteinase have been observed in the polypeptide
      at position + 31 and + 38. The putative amino acid sequence showed a significant
      similarity to a surface layer protein of L. helveticus and Lactobacillus
      acidophilus in the amino terminal signal sequence and carboxyl terminus.

PMID- 10923795
TI  - Purification, characterization, and molecular cloning of acidophilic xylanase
      from penicillium sp.40.
AB  - Penicillum sp. 40, which can grow in an extremely acidic medium at pH 2.0 was
      screened from an acidic soil. This fungus produces xylanases when grown in a
      medium containing xylan as a sole carbon source. A major xylanase was purified
      from the culture supernatant of Penicillium sp. 40 and designated XynA. The
      molecular mass of XynA was estimated to be 25,000 by sodium dodecyl sulfate
      polyacrylamide gel electrophoresis. XynA has an optimum pH at 2.0 and is stable
      in pH 2.0-5.0. Western blot analysis using anit-XynA antibody showed that XynA
      was induced by xylan and repressed by glucose. Also, its production was increased
      by an acidic medium. The gene encoding XynA (xynA) was isolated from the genomic
      library of Penicillium sp. 40. The structural part of xynA was found to be 721
      bp. The nucleotide sequence of cDNA amplified by RT-PCR showed that the open
      reading frame of xynA was interrupted by a single intron which was 58 bp in size
      and encoded 221 amino acids. Direct N-terminal amino acid sequencing showed that
      the precursor of XynA had a signal peptide composed of 31 amino acids. The
      molecular mass caliculated from the deduced amino acid sequence of XynA is
      20,713. This is lower than that estimated by gel electrophoresis, suggesting that
      XynA is a glycoprotein. The predicted amino acid sequence of XynA has strong
      similarity to other family xylanases from fungi.

PMID- 10923794
TI  - Synthesis of novel heterobranched beta-cyclodextrins from 4(2)-O-beta-D
      galactosyl-maltose and beta-cyclodextrin by the reverse action of pullulanase,
      and isolation and characterization of the products.
AB  - From the mixture of 4(2)-O-beta-D-galactosyl-maltose (Gal-G2) and beta
      cyclodextrin (betaCD), novel heterobranched betaCDs, (Gal-G2)-betaCD and (Gal
      G2)2-betaCDs, were synthesized by the reverse action of debranching enzyme. The
      optimum conditions for the production of (Gal-G2)2-betaCDs were examined. A
      mixture of (Gal-G2)2-betaCDs was produced in about 4% yield when Aerobacter
      aerogenes pullulanase (64 units per 1 g of Gal-G2) was incubated with 1.6 M Gal
      G2 and 0.16 M betaCD at 50 degrees C for 4 days. The reaction products, (Gal-G2)2
      betaCDs, were separated into three peaks by HPLC analysis on a Hypercarb S
      column. Their structures were analyzed by fast atom bombardment mass spectroscopy
      and NMR spectroscopies, and confirmed by comparison of their hydrolyzates by beta
      galactosidase with the authentic (G2)2 -betaCDs. The structures of (Gal-G2)
      betaCD and three components of (Gal-G2)2-betaCDs were identified as 6-O-(GalG2)
      betaCD, 6(1),6(2)-, 6(1),6(3)- and 6(1),6(4)-di-O-(Gal-G2)2-betaCD, respectively.

PMID- 10923796
TI  - Cloning and sequencing of an endoglucanase gene from Scopulariopsis brevicaulis
      TOF-1212, and its expression in Saccharomyces cerevisiae.
AB  - The egI gene, encoding a major endoglucanase (EGI) of Scopulariopsis brevicaulis
      TOF-1212, was cloned and sequenced. The eglgene consisted of 868 bp with one
      intron and encoded a protein of 229 amino acids with a calculated molecular mass
      of 22,392 daltons. The EGI was assigned to a family 45 of glycosyl hydrolases and
      showed high similarity with other fungal endoglucanases, especially with those of
      Humicola grisea and Fusarium oxysporum, on the basis of hydrophobic cluster
      analysis. The egI gene was expressed under the promoter of the phosphoglycerate
      kinase gene (PGK) in Saccharomyces cerevisiae. The transformed cells were able to
      secrete the enzyme efficiently in an active form.

PMID- 10923798
TI  - Purification and characterization of a novel lactonohydrolase from Agrobacterium
      tumefaciens.
AB  - A novel lactonohydrolase, catalyzing the stereospecific hydrolysis of L-pantoyl
      lactone to L-pantoic acid, was purified 2,400-fold to apparent homogeneity with a
      1.96% overall recovery from Agrobacterium tumefaciens AKU 316 through a
      purification procedure including ammonium sulfate fractionation, and column
      chromatographies on DEAE-Sephacel, phenyl-Sepharose CL-4B, Sephacryl S-200, Mono
      Q and alkyl-Superose. The relative molecular mass of the native enzyme estimated
      on high-pressure gel permeation chromatography was 62,000 Da, and the subunit
      molecular mass was estimated to 26,500 Da on SDS-polyacrylamide gel
      electrophoresis. The enzyme hydrolyzes several aromatic lactones, such as 3,4
      dihydrocoumarin and homogentisic acid lactone, other than L-pantoyl lactone. The
      Km and Vmax for L-pantoyl lactone were 3.59 mM and 13.7micromol/min/mg,
      respectively. The enzymatic activity was inhibited by several chelating reagents,
      Fe2+, Sn2+, Pb2+, and Fe3+.

PMID- 10923797
TI  - Cloning and sequence analysis of cDNA coding for a lectin from Helianthus
      tuberosus callus and its jasmonate-induced expression.
AB  - Two lectins (designated as HTA I and HTA II) that seemed to be isolectins were
      found in Helianthus tuberosus callus. cDNA encoding HTA I was isolated from a ZAP
      Express expression library by immunoselection by using the anti-HTA antiserum.
      The sequence of this cDNA consisted of 432 bp nucleotides coding for a
      polypeptide of 143 amino acid residues (Mr, 15,314). When introduced into E.
      coli, the cDNA directed the synthesis of active HTA I as indicated by the
      hemagglutination activity. The deduced amino acid sequence showed homology with
      some lectins and jasmonate-induced proteins. When callus was cultured in the
      presence of methyl jasmonate (MeJA), the hemagglutination activity increased in a
      dose-dependent manner. The levels of expression of the HTA protein and of the
      corresponding mRNA also increased in the treated callus. In view of these
      results, HTA I is considered to be a jasmonate-induced protein.

PMID- 10923799
TI  - Overproduction of microbial transglutaminase in Escherichia coli, in vitro
      refolding, and characterization of the refolded form.
AB  - (MTG) The Streptoverticillium transglutaminase gene, synthesized previously for
      yeast expression, was modified and resynthesized for overexpression in E. coli. A
      high-level expression plasmid, pUCTRPMTG-02(+), was constructed. Furthermore, to
      eliminate the N-terminal methionine, pUCTRPMTGD2 was constructed. Cultivation of
      E. coli transformed with pUCTRPMTG02(+) or pUCTRPMTGD2 yielded a large amount of
      MTG (200-300 mg/liter) as insoluble inclusion bodies. The N-terminal amino acid
      residue of the expressed protein was methionine or serine (the second amino acid
      residue of the mature MTG sequence), respectively. Transformed E. coli cells were
      disrupted, and collected pellets of inclusion bodies were solubilized with 8 M
      urea. Rapid dilution treatment of solubilized MTG restored the enzymatic
      activity. Refolded MTG, purified by ion-exchange chromatography, which had an N
      terminal methionine or serine residue, showed activity equivalent to that of
      native MTG. These results indicated that recombinant MTG could be produced
      efficiently in E. coli.

PMID- 10923800
TI  - Cerebrosides in grapevine leaves: distinct composition of sphingoid bases among
      the grapevine species having different tolerances to freezing temperature.
AB  - Cerebrosides from leaves of three grapevine species were analyzed in detail. The
      relative proportions of 8-E/Z isomers of 4-hydroxy-8-sphingenines [i.e. 8-E/Z
      t18:1(8E) and (8Z)] differed amongst the species in respect to freezing
      tolerance. This suggests that the occurrence of high levels of t18:1(8Z) in
      cerebrosides is correlated with freezing tolerance in these species.

PMID- 10923801
TI  - Protective effect of phenolic antioxidants on the cytotoxicity induced by
      phosphatidylcholine hydroperoxide.
AB  - Phosphatidylcholine hydroperoxides show weak but distinct toxicity toward
      cultured human umbilical vein endothelial cells. The protective effect of
      phenolic antioxidants against the cytotoxicity of phosphatidylcholine
      hydroperoxides was examined. Probucol depressed the toxicity most effectively
      among the antioxidants studied under both pretreatment and concurrent treatment
      conditions. alpha-Tocopherol showed a protective effect in the case of concurrent
      treatment. Protection by phenolic antioxidants against the cytotoxicity of
      phosphatidylcholine hydroperoxides seems to depend on their incorporation rate
      into cells, their affinity for phospholipids, their antioxidative activity, and
      their orientation in membranes.

PMID- 10923803
TI  - Non-effect of hexamethonium, a ganglionic blocker, on the response of ileal
      apolipoprotein A-IV mRNA following a massive small bowel resection in rats.
AB  - An intravenous infusion of hexamethonium, a ganglionic blocker, did not affect
      the increase in the apolipoprotein A-IV mRNA level in the residual ileum
      following a massive small bowel resection in unrestrained conscious rats. The
      result suggests that upregulation of the apolipoprotein A-IV gene in the residual
      ileum is not mediated by a neural pathway, including the nicotinic synapse route.

PMID- 10923802
TI  - Effects of chemical modification of carboxyl groups in the hemolytic lectin CEL
      III on its hemolytic and carbohydrate-binding activities.
AB  - Effects of chemical modification of carboxyl groups in the hemolytic lectin CEL
      III on its activities were investigated. When carboxyl groups were modified with
      1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and glycine methyl ester,
      hemolytic activity of CEL-III decreased as the EDC concentration increased,
      accompanied by reduction of oligomerization ability and hemagglutinating
      activity. However, binding ability of CEL-III for immobilized lactose was
      retained fairly well after modification, suggesting that one of two carbohydrate
      binding sites might be responsible for such inactivation of CEL-III.

PMID- 10923804
TI  - Detection of protease activity with a fluorescence-labelled peptide substrate on
      a TLC plate.
AB  - A small amount of peptidase activity could be detected using an amine
      derivatizing reagent, fluorescein isothiocyanate (FITC), which has been used to
      produce a fluorogenic peptide. The substrate produced, FITC-peptide, gave a clear
      spot on a silica gel sheet upon exposure to UV light. The peptidase activity of
      angiotensin-converting enzyme (ACE), trypsin, chymotrypsin, cucumisin, and that
      of some plant tissues were detected by using a fluorogenic angiotensin I. This
      showed that the substrate specificity of proteolytic enzymes can be distinguished
      from the others by this procedure.

PMID- 10923805
TI  - Assay of DNA photolyase activity in spinach leaves in relation to cell
      compartmentation-evidence for lack of DNA photolyase in chloroplasts.
AB  - Spinach cyclobutane pyrimidine dimer (CPD)-specific DNA photolyase was
      successfully detected in leaf extracts by an assay system for plant photolyase
      using an improved enzyme-linked immunosorbent assay (ELISA) which was newly
      introduced by novel horseradish peroxidase (HRP)-linked CPD specific monoclonal
      antibodies. The assay system includes two main steps: a photorepair reaction of
      CPD introduced in substrate DNA and measurement of CPD remained after the
      photorepair by the improved ELISA. When CPD- induced salmon sperm DNA was used as
      a substrate, high CPD-photolyase activities were observed in the enzyme fraction
      prepared from whole spinach leaf extracts, but not from chloroplast extracts.
      This strongly suggests that spinach CPD-specific photolyases are localized in
      cell compartments other than chloroplasts.

PMID- 10923806
TI  - Application of a single-cell gel electrophoresis (comet) assay to screen the
      antimutagenic activity in foods.
AB  - Three cell lines (HL60, U937 and RAW264.7) were studied for their sensitivity
      against mutagens by using a single-cell gel electrophoresis (comet) assay.
      RAW264.7, the most sensitive one, was chosen to screen the antimutagenic activity
      in swine and bovine offal. Aqueous extracts of the swine stomach (0.2 mg/ml) and
      heart (10 mg/ml) were found to have antimutagenic activity against MeIQx (+
      S9mix)-treated cells.

PMID- 10923807
TI  - Unfolding of poly-L-glutamic acid by microbubbling of supercritical carbon
      dioxide.
AB  - The conformational changes in alpha-helical poly-L-glutamic acid caused by
      microbubbling supercritical CO2 were investigated with circular dichroism
      spectra. After microbubbling using a micropore filter at 35 and 30 MPa for 30
      min, alpha-helix content decreased to 37%, while without the filter it was 68%.
      The alpha-helix structure was significantly decomposed by a high density of CO2.
      No important changes were observed in heating, autoclaving, or pH-lowering.

PMID- 10923808
TI  - Construction of mutants of Sphingomonas paucimobilis defective in terminal
      mannose in the glycosphingolipid.
AB  - Mutants of Sphingomonaspaucimobilis defective in a part of the carbohydrate
      moiety of the glycosphingolipid (GSL) were constructed by transposon (Tn5)
      insertional mutagenesis. Defective mutants were selected by ELISA using the
      antibody recognizing the tetrasaccharide-type GSL (GSL-4A) of S. paucimobilis.
      Eight defective mutants were selected from about 8,000 kanamycin-resistant
      strains, and seven of them were found to lack the terminal mannose of GSL-4A. The
      chemical structure of the mutant GSL was investigated, and proved that the rest
      of the structure was not changed by the mutation.

PMID- 10923809
TI  - Effects of bacterial glyceroglycolipid M874B on growth and TPA-induced
      differentiation of HL60 cells.
AB  - Bacterial monogalactosyldiacylglycerol M874B (MGDAG), which protects against
      oxygen radicals, was found to increase the growth of the human promyelocytic
      leukemia cell HL60 when added to the cell culture, but suppresses the 12-O
      tetradecanoyl phorbol-13-acetate-induced differentiation. Analogous MGDAG, S365B
      had weak, but similar effects. These activities were not observed with analogous
      plant glyceroglycolipids and diacylglycerol.

PMID- 10923810
TI  - Isolation and sequencing of a cDNA clone encoding a 20-kDa protein with trypsin
      inhibitory activity.
AB  - The amino acid sequence of a novel trypsin inhibitor (p20) was completed by the
      molecular cloning of the protein in cultured soybean cells. The clone nucleotide
      contains an open reading frame encoding a polypeptide of 206 amino acids that
      shows 45-50% sequence homology to members of the Kunitz-type trypsin inhibitor
      family. The p20 transcript is expressed in the roots, stems and leaves of soybean
      seedlings. DNA gel blot analyses show that the p20 in soybean is encoded by a
      single gene, and that this gene may not contain an intron.

PMID- 10923811
TI  - New insecticidal bufadienolide, bryophyllin C, from Kalanchoe pinnata.
AB  - Two insecticidal bufadienolides (1 and 2) were isolated from a methanol extract
      of the leaves of Kalanchoe pinnata by bioassay-guided fractionation. Compound 1
      was identified as known bryophyllin A (bryotoxin C). The structure of new
      bufadienolide 2, named bryophyllin C, was determined by spectroscopic methods and
      the chemical transformation of 1. Compounds 1 and 2 showed strong insecticidal
      activity against third instar larvae of the silkworm (Bombyx mori), their LD50
      values being evaluated as 3 and 5 microg/g of diet, respectively.

PMID- 10923812
TI  - Positions of disulfide bonds in rye (Secale cereale) seed chitinase-a.
AB  - The positions of disulfide bonds of rye seed chitinase-a (RSC-a) were identified
      by the isolation of disulfide-containing peptides produced with enzymatic and/or
      chemical cleavages of RSC-a, followed by sequencing them. An unequivocal
      assignment of disulfide bonds in this enzyme was as follows: Cys3-Cysl8, Cys12
      Cys24, Cys15-Cys42, Cys17-Cys31, and Cys35-Cys39 in the chitin-binding domain (CB
      domain), Cys82-Cys144, Cys156-Cys164, and Cys282-Cys295 in the catalytic domain
      (Cat domain), and Cys263 was a free form.

PMID- 10923813
TI  - A beta-rutinosidase from Penicillium rugulosum IFO 7242 that is a peculiar
      flavonoid glycosidase.
AB  - A beta-rutinosidase, which was specific for releasing the disaccharide rutinose
      from the flavonoid glycoside rutin, was purified from Penicillium rugulosum IFO
      7242. This enzyme had the molecular weight of 245,000, a very low optimum pH of
      2.2, and the remarkable specificity that the glycosidase did not hydrolyze any
      other substrates like 4-nitrophenyl beta-glucoside and cellobiose, but only rutin
      and isoquercitrin.

PMID- 10923814
TI  - Resorufin as an electron acceptor in glucose oxidase-catalyzed oxidation of
      glucose.
AB  - Resorufin (1) has been found to act as an electron acceptor in glucose oxidase
      (GOD)-catalyzed oxidation of glucose. When a 1: 1: 1 mixture of solutions of 1
      (5.0 microM), glucose, and GOD (4.0 mg/ml) in phosphate buffer (pH 7.4, 0.1 M)
      was incubated at 36 degrees C under aerobic conditions and the reaction was
      followed by a measurement of changes in fluorescence intensity due to 1, only two
      types of fluorometric traces were observed: (1) when a glucose solution of less
      than 0.7 mM was subjected to the enzymatic reaction, no consumption of 1 was
      observed; (2) the reaction with glucose at more than 1.0 mM always consumed 1,
      affording a regression fluorometric curve, and yet the obtained fluorometric
      traces could be almost superimposed on one another with no dependence on the
      glucose concentration. The reasons for the observed phenomena are discussed.

PMID- 10923817
TI  - Mononuclear and polynuclear chelates of picolinoyldithiocarbazate.
AB  - Mononuclear and polynuclear chelates of potassium picolinoyldithiocarbazate
      (KHPcDC) with Mn(II), Fe(ll1), Fe(II), Co(Il), Ni(II), Cu(II), Zn(II), Cd(II),
      Hg(II), Pd(II) and U(VI)O2 have been prepared and characterized by chemical and
      thermal (TG, DTG, DTA) analyses, molar conductivities, spectral (UV-Visible, IR,
      NMR, ESR) and magnetic moment measurements. The molar conductivities of the
      complexes lie in the non-electrolyte range whilst KHPcDC is a 1:1 electrolyte.
      Changes in selected vibrational absorption of the ligand upon coordination
      indicate that KHPcDC behaves as monoanionic and coordinates in a bidentate,
      tridentate and/or bridging tetradentate manner. Trans-form structure is proposed
      for [Pd(HPcDC)2] x 2H20 and [Cd(HPcDC)2] complexes on the basis of NMR data. An
      octahedral structure is proposed for Fe(III), Fe(II) and Ni(II) complexes, a
      square-planar structure for Co(II) and Pd(II) complexes and a tetragonally
      distorted octahedral structure for the Cu(II) chelate on the basis of
      spectroscopic and magnetic data. The ligand field parameters (B, Dq, beta) for
      the Fe(III) and Ni(II) chelates were calculated. TG, DTG and DTA studies support
      the different modes of chelation of KHPcDC. The solid metal acetate chelates have
      a unique decomposition exotherm profile which can be used as a rapid and
      sensitive tool for the detection of acetate-containing complexes.

PMID- 10923816
TI  - Autoxidation of ascorbic acid catalyzed by the copper(II) bound to L-histidine
      oligopeptides, (His)iGly and acetyl-(His)i Gly (i=9, 19, 29). Relationship
      between catalytic activity and coordination mode.
AB  - Spectroscopic and kinetic studies on the autoxidation of ascorbic acid catalyzed
      by copper complexes of histidine oligopeptides, (His)iGly (i=4, 9, 19, 29), and
      their acetyl derivatives, Ac-(His)iGly (i=9, 19) have been carried out at pH 4.4
      and 25 degrees C under dioxygen. The reaction was monitored at 260 nm using a
      stopped-flow spectrophotometric technique. The reaction fitted the "Michaelis-
      Menten" mechanism, and ascorbate was oxidized by the "Ping-Pong" mechanism. The
      Cu(lI) complexed with the oligopeptide (i > or = 9) enhanced the reaction
      approximately two-fold relative to the aqueous Cu(II). The catalytic activity
      depends on the molecular weight which is related to the number of histidyl
      residues and on the coordination mode of the copper-binding site. Results of
      circular dichroism (CD) experiments revealed the existence of two types of
      Cu(II). The catalytically active Cu(II), which is accommodated in the imidazole
      clusters composed of at least six histidyl residues, exhibits d-d transition
      bands at 520 and 630 nm, and is easily dissociable, enhances the autoxidation; Ac
      (His)19Gly is likely to accommodate approximately three active Cu(II) ions. The
      Cu(II), which is complexed tightly with the terminal H2N-X-Y-His- moiety, where X
      and Y denote amino acids, inhibits the autoxidation, and exhibits absorption
      bands at 480 and 550 nm.

PMID- 10923815
TI  - Synthesis and biological activities of 2-arachidonoylglycerol, an endogenous
      cannabinoid receptor ligand, and its metabolically stable ether-linked analogues.
AB  - We synthesized 2-arachidonoylglycerol (1), an endogenous cannabinoid receptor
      ligand, and its metabolically stable ether-linked analogues. Compound 1 was
      synthesized from 1,3-benzylideneglycerol (6) and arachidonic acid in the presence
      of N,N'-dicyclohexylcarbodiimide and 4-dimethylaminopyridine followed by
      treatment with boric acid and trimethyl borate. An ether-linked analogue of 2
      arachidonoylglycerol (2) was synthesized from 6 and 5,8,11,14-eicosatetraenyl
      iodide (9). The ether-linked analogues of 2-palmitoylglycerol (4) and 2
      oleoyglycerol (5) were synthesized from 6 and hexadecyl iodide (12) and 9
      octadecenyl iodide (14), respectively. We confirmed that 1 stimulates NG108-15
      cells to induce rapid transient elevation of the intracellular free Ca2+
      concentrations through a CB1 receptor-dependent mechanism. Noticeably, 2
      exhibited appreciable agonistic activity, although its activity was significantly
      lower than that of 1. Compound 2 would be a useful tool in exploring the
      physiological significance of 1, because this compound is resistant to
      hydrolyzing enzymes in contrast to 1. On the other hand, the ether-linked
      analogues of either 4 or 5 failed to act as a CB1 receptor agonist. Compounds 4
      and 5 would also be valuable as control molecules in experiments where 2 is
      employed.

PMID- 10923818
TI  - Synthesis, conformation, and chemical properties of new mini parallel double
      stranded peptides conjugated with -Phe-Phe- and -Phe-Phe-X-sequences.
AB  - To investigate the chemical conformations and functions of the -Phe-Phe-Val- or 
      Phe-Phe- sequences contained in the Alzheimer's disease related beta-amyloid
      peptide, a series of mini parallel double-stranded peptides conjugated with two
      peptide residues to one spacer were designed and prepared. The structure of the
      compounds was elucidated by circular dichroism (CD) spectrum and NMR two
      dimensional (2D) nuclear Overhauser enhancement and exchange spectroscopy (NOESY)
      measurments. The structure of 1,2-ethano-bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano
      bis(L-Phe-L-Phe-L-Leu), 1,12-dodecano-bis(L-Phe-L-Phe-L-Val), and 1,12-dodecano
      (D-Phe-D-Phe-D-Leu) conjugated with L-Leu and L-Val residues show a beta-turn
      like nucleation. The dihedral angles (theta = +75 degrees, omega = +180 degrees,
      phi = +90 degrees, phi = -87 degrees, psi = +180 degrees) obtained from
      experimental coupling constant (J) data, etc. support that 1,12-dodecano-bis(L
      Phe-L-Phe) adopts beta-turn mimic nucleation. The 1,12-dodecano- bis(L-Leu-L-Leu
      L-Phe), 1,12-dodecano-bis(L-lle-L-Phe-L-Leu), and 1,12-dodecano-bis(L-Phe-L-Val-L
      Leu), etc. adopt most probably a random structure by CD studies. It was found by
      titration spectrum that an inclusion complex of 1:1 ratio (association constant;
      azobenzene (guest, Ka=1.0 x 10(4)M-1) is formed between 1,12-dodecano-bis(L.-Phe
      L-Phe-L-Leu) and [L0]=1.758 x 10(-5)M-1). Moreover, the stability of the
      complexes was increased in order of 1,12-dodecano-bis(L-Phe-L-Phe-L-Leu) x
      azobenzene> 1,12-dodecano-bis(L-Phe-L-Phe-L-Val) x azobenzene> 1,12-dodecano
      bis(L-Phe-L-Val-L-Leu) azobenzene. The data show that X-Phe-L-Phe-L-spacer(S)-L
      Phe-L-Phe-X (X=amino acids; S = 1,2-ethano- and 1,12-dodecano-) plays an
      important role as a binding site of the artificial receptor. The hydrophobic
      interaction of the four Phes in the two strands is a very interesting issue in
      the physiological action of proteins as well as the conformation of the backbone
      of X-L-Phe-L-Phe-spacer(S)-iL-Phe-l.-Phe-X.

PMID- 10923819
TI  - Synthesis of diaryl-substituted imidazo[l,2-a]pyridines designed as potential
      aromatase inhibitors.
AB  - From a pharmacophore model of bicyclic heterocycles as aromatase inhibitors we
      have designed three series of imidazo[1,2-a]pyridine derivatives. The synthesis
      and the spectroscopy determination of various compounds are reported. The crystal
      data of one of these compounds (10b) was obtained. The aromatase inhibition
      potency was evaluated in vitro and no activity was found.

PMID- 10923820
TI  - PEC films prepared from Chitosan-Alginate coacervates.
AB  - Chitosan-alginate polyelectrolyte complex (PEC) have been prepared in situ in
      beads and microspheres. This study examines the preparation of suitable chitosan
      alginate coacervates for casting into homogeneous PEC films for potential
      applications in packaging, controlled release systems and wound dressings.
      Coacervation between chitosan and alginate was rapid, but the rate may be
      controlled with the addition of water miscible organic solvents. Compared with
      ethanol and PEG200, acetone was the more promising solvent moderator. Suspensions
      of fine, uniformly dispersed coacervates were produced by a dropwise addition of
      0.25% w/v chitosan solution (solvent: 1: 1 v/v of 2% acetic acid and acetone)
      into 0.25% w/v sodium alginate solution in water under rapid agitation. The PEC
      films were transparent and flexible. They exhibited high permeability to water
      vapor, but resisted complete dissolution in 0.1 M HCI, distilled water and pH 7.4
      phosphate buffer solution. Microscopic heterogeneity in the films could be
      reduced by immersion in aqueous media, but this was accompanied by modifications
      in the thickness, permeability and mechanical property of the films.

PMID- 10923821
TI  - Formation of spherical micelles by the novel platelet activating factor receptor
      antagonist, E5880.
AB  - E5880, a novel platelet activating factor receptor antagonist, was dispersed in
      water for the preparation of injectable formulation and the physicochemical
      properties of the micelles were characterized. The critical concentration for
      formation of micelles was 0.12 mM. Using the area per molecule results, the
      critical packing parameter was calculated and showed that the structure was
      composed of spherical micelles and the number of the molecules per micelle was
      88. The diameter of a micelle was 8.1 nm. The fluidity and micropolarity around
      the hydrocarbon region of the micelles were evaluated and compared to the
      surfactants, stearyltrimethylammmonium chloride and cetyltrimethylammonium
      chloride.

PMID- 10923823
TI  - Difference spatial distribution function analysis of aqueous solutions. III.
      Hydration structures of alcohol and ether solutions having straight chain and
      branched alkyl groups.
AB  - Spatial distribution functions (SDFs), gOO(x,y,z) and gOH(x,y,z), obtained from
      Monte Carlo simulations at 298 K were applied to characterize the anisotropic
      structure of infinitely dilute aqueous solutions of alcohols and ethers having
      straight chain and branched alkyl groups. In spite of the different size and
      shape of the hydrophobic groups, the spatial orientation of the hydrogen-bonded
      water molecules was found to be of linear type with a triple layer structure in
      the hydrogen acceptor (HA) region and a double layer structure in the hydrogen
      donor (HD) region. The volumes and the coordination number (CN) in the HA region
      were essentially identical for all alcohol and ether solutions, but the volumes
      for the isopropyl alcohol (IPA) and isopropyl methyl ether (IPE) solutions were
      greater than those for the other solutions. In the hydrophobic hydration (HH)
      region, these values increased with increasing size and shape of hydrophobic
      groups, except in the case of IPA and IPE solutions. These results indicated that
      the hydration structures around the isopropyl group in alcohol and ether
      solutions differed from those in other solutions. From the results of the
      difference SDF (DSDF), AgOO(x,y,z), between SDFs gOO(x,y,z) for the two states,
      it was apparent that the distribution of hydration water molecules in the HA
      region for ether solution was characterized by the increase of the distribution
      in the direction of lone pair electrons on the oxygen atom of the solute molecule
      with increasing hydrophobicity.

PMID- 10923822
TI  - The shell dissolution of various empty hard capsules.
AB  - The shell dissolution properties of gelatine, gelatine/polyethylene glycol (PEG)
      and hydroxypropyl methylcellulose (HPMC) capsules were studied as a function of
      temperature, dissolution medium, and after different storage conditions. In any
      dissolution medium with a pH below or equal to 5.8, HPMC capsule shells dissolved
      rapidly, and there was no difference in the time in which dissolution occurred in
      the tested temperature interval of 10 to 55 degrees C. Gelatine and gelatine/PEG
      capsule shells, generally, did not dissolve at temperatures below 30 degrees C.
      The shell dissolution time of all capsules tested was prolonged and more variable
      in mixed phosphate buffer pH = 6.8. The addition of enzymes (pepsin, pancreatin)
      to any dissolution medium was found not to enhance the differences between the
      different types of capsules investigated. In practical terms, the results
      indicated that capsule formulations should not be taken with drinks from the
      carbonated Cola-type. Gelatine containing capsules should preferably be
      administered with a warm drink, whereas HPMC capsules could be given with cold or
      warm drinks. The latter type of capsules should also be preferred for
      preparations to be taken in the fasted state. A short storage of gelatine
      containing capsules under hot humid tropical conditions appeared not to alter the
      dissolution properties of the shells, and changes in disintegration times and
      dissolution times of formulations filled in such capsules might be a reflection
      of changes of the powders incorporated rather than of the capsule shells.
      However, a short storage of HPMC capsules under such conditions appeared to
      influence the capsule shell matrix.

PMID- 10923824
TI  - Synthesis and anti-platelet, anti-inflammatory and anti-allergic activities of
      methoxyisoflavanquinone and related compounds.
AB  - In a continuation of our search for novel anti-platelet agents, isoflavone
      quinone and isoflavanquinone were selected as lead compounds and the synthesis of
      their methoxy derivatives was carried out. Among them, the 4'- and 7-methoxy
      derivatives were successfully prepared, whereas the attempt to obtain 3'-methoxy
      derivatives resulted in their isomers, 3'-methoxyflavone quinone and 3'
      methoxyflavanquinone, instead. After screening for their anti-platelet, anti
      inflammatory and anti-allergic activities, a preliminary structure-activity
      relationship was established. Compounds 6c, 7a-c, 8c and 9a-c were found to
      exhibit significant activities. In particular, compound 7c demonstrated very
      potent anti-platelet, anti-inflammatory and anti-allergic activities and was then
      recommended for further pharmacological investigation.

PMID- 10923826
TI  - Studies on adsorption characteristics of bile acids and methotrexate to a new
      type of anion-exchange resin, colestimide.
AB  - The adsorption characteristics of various bile acids and methotrexate to a new
      type of anion-exchange resin, colestimide, were studied in vitro and compared
      with those to cholestyramine. For bile acids, colestimide was shown to have a
      higher capacity than cholestyramine. For example, approximately 1.4-fold higher
      for cholic acid and 2.0-fold for deoxycholic acid in water. In the presence of
      physiological anions, the degree of adsorption of cholic acid to both resins was
      greatly reduced, whereas adsorption of deoxycholic acid was only slightly
      reduced. Furthermore, the bed-volume of colestimide swelled about 6.8-fold in
      water, hence the anion-exchange groups of this resin are expected to be able to
      function effectively in adsorption of bile acids in the gut. In addition,
      colestimide was found to have high adsorption capacity for methotrexate, not only
      in water but also in media containing various physiological anions, and thus it
      is suggested that colestimide is a potential oral antidote to reduce possible
      toxicity by methotrexate through interruption of enterohepatic circulation.

PMID- 10923825
TI  - Pyrinodemins B-D, potent cytotoxic bis-pyridine alkaloids from marine sponge
      amphimedon sp.
AB  - New bis-pyridine alkaloids, pyrinodemins B-D (1-3), have been isolated together
      with pyrinodemin A (4) and related 3-alkyl pyridine alkaloids 5-8 from the
      Okinawan marine sponge Amphimedon sp. and the structures were elucidated from
      spectroscopic data. Pyrinodemins B-D (1-3) showed potent cytotoxicity, while
      compounds 5-8 exhibited antimicrobial activity.

PMID- 10923827
TI  - New antifungal 1,2,4-triazoles with difluoro(heteroaryl)methyl moiety.
AB  - New 1,2,4-triazoles (1) having a difluoro(heteroaryl)methyl moiety were designed
      and synthesized via 1-aryl-2,2-difluoro-2-(heteroaryl)ethanones (2), which were
      prepared by two routes starting from the reaction of ethyl 2,2
      difluoro(heteroaryl)acetate with phenyllithiums (Route A) and from the reaction
      of chlorodifluoro(heteroaryl)methane with benzaldehydes (Route B). The compounds
      1 except for 1g show antifungal activities against yeasts and filamentous fungi
      in vitro, especially (+)-1f have equal or superior activities compared to those
      of itraconazole.

PMID- 10923828
TI  - An androstane bioside and 3'-thiazolidinone derivatives of doubly-linked
      cardenolide glycosides from the roots of Asclepias tuberosa.
AB  - Steroidal compounds in the roots of Asclepias tuberosa were investigated and
      17alpha-hydroxyandrosta-4,6,15-trien-3-one 17-O-alpha-L-arabinopyranosyl-(1-->6)
      beta-D-glucopyranoside, termed ascandroside, was isolated from the CHCl3-soluble
      fraction. Among five doubly-linked cardenolide glycosides, two were identified as
      3'-spiro-linked thiazolidinone (4) and S-oxythiazolidinone derivatives (5) of
      delta5-calotropin. The stereochemistry at the C-3' in these two cardenolides is
      discussed. 3'-O-beta-D-Glucopyranosyl-delta5-calotropin (3) was also isolated
      along with A5-calotropin and its 3'-acetate. Nine glycosides of uzarigenin,
      coroglaucigenin and corotoxigenin were identified.

PMID- 10923830
TI  - Stilbenoids isolated from stem bark of Shorea hemsleyana.
AB  - Two new stilbene glucosides [(+)-alpha-viniferin 13b-O-beta-glucopyranoside and
      resveratrol 12-C-beta-glucopyranoside] and two new resveratrol oligomers,
      hemsleyanols A and B, were isolated from the bark of Shorea hemsleyana along with
      four known resveratrol oligomers. The structures of the isolates, including the
      relative configurations, were established by spectroscopic data involving long
      range coupling and nuclear Overhauser effect experiments.

PMID- 10923829
TI  - Medicinal foodstuffs. XVII. Fenugreek seed. (3): structures of new furostanol
      type steroid saponins, trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa, from the
      seeds of Egyptian Trigonellafoenum-graecum L.
AB  - Six new furostanol-type steroid saponins called trigoneosides Xa, Xb, XIb, XIIa,
      XIIb, and XIIIa were isolated from the seeds of Egyptian Trigonella foenum
      graecum L. (Leguminosae) together with six known furostanol-type steroid
      saponins: trigoneosides Ia, Ib, and Va, glycoside D, trigonelloside C, and
      compound C. The structures of trigoneosides Xa, Xb, Xlb, XIIa, Xllb, and XIIIa
      were determined on the basis of chemical and physicochemical evidence as 26-O
      beta-D-glucopyranosyl-(25S)-5alpha-furostane-2alpha+ ++,3beta,22xi,26-tetraol 3-O
      alpha-L-rhamnopyranosyl(1-->2)-,beta-D-glucopyranoside, 26-O-beta-D
      glucopyranosyl-(25R)-5alpha-furostane-2 alpha,beta,22xi,26tetraol 3-O-alpha-L
      rhamnopyranosyl(l -->2)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)
      5alpha-furostane2alpha++ +,beta,22xi,26-tetraol 3-O-beta-D-xylopyranosyl(l -->4)
      beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25S)-furost-4-ene
      3beta,22xi,26- triol 3-O-Ca-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, 26-O
      beta-D-glucopyranosyl-(25R)-furost-4-ene-3beta,22xi+ ++,26-triol 3-O-alpha-L
      rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, and 26-O-beta-D
      glucopyranosyl(25S)-furost-5-ene-3beta,22xi,26-t riol 3-O-alpha-L
      rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl (1-->3)-beta-D-glucopyranosyl(1--4)]
      beta-D-glucopyranoside, respectively.

PMID- 10923832
TI  - Polymer-Supported dicyanoketene acetal as a pi-acid catalyst:
      monothioacetalization and carbon-carbon bond formation of acetals.
AB  - Polymeric dicyanoketene acetals (DCKA) were synthesized by copolymerization of
      styrene and divinylbenzene or ethylene glycol dimethacrylate. These novel
      polymers could be used successfully as recyclable pi-acid catalysts in
      monothioacetalization or carbon-carbon bond forming reaction of acetals.

PMID- 10923831
TI  - The constituents of the root and stem of Aristolochia cucurbitifolia Hayata and
      their biological activity.
AB  - Four new compounds, three phenanthrene derivatives, aristolochic acid-III methyl
      ester (1), cepharanone C (2), and sodium 7-hydroxyl-8-methoxyaristolate (3), and
      the benzoate derivative, sodium 3,4-dimethoxybenzoate (4), together with 53 known
      compounds were isolated and characterized from the fresh root and stem of
      Aristolochia cucurbitifolia. Their structures were elucidated by spectral
      analyses and chemical transformations. The cytotoxicity and antiplatelet activity
      of the isolated compounds are also discussed.

PMID- 10923833
TI  - Pregnane glycosides from the roots of Asclepias tuberosa.
AB  - Sixteen glycosides of pregnanes, including ikemagenin, lineolon, and a new
      pregnane, 3beta8beta,14beta,15beta,16alpha-pentahydroxy-++ +5alpha-pregnan-20
      one, termed pleurogenin, were isolated from the roots of Asclepias tuberosa.
      Among ikemagenin and lineolon glycosides, one (1) was a known glycoside, and
      eight (2-7, 10, 13) were glycosides with new combinations of ikemagenin or
      lineolon and known sugar sequences composed of D-cymarose, D-oleandrose, D
      thevetose and D-glucose. The structures of four new glycosides of ikemagenin (8,
      9, 11, 12) and three of pleurogenin (14-16) were determined. The new glycosides
      have sugar sequences ranging from tetraoside to heptaosides.

PMID- 10923834
TI  - Michael-type reaction of ethyl bromodifluoroacetate with alpha,beta- unsaturated
      carbonyl compounds in the presence of copper powder.
AB  - We have reported that the reaction of ethyl bromodifluoroacetate (1) with alkenyl
      iodides in the presence of copper powder gives ethyl alkenyldifluoroacetates. As
      an extension of this reaction, reaction of 1 with Michael acceptors in the
      presence of copper powder was examined and found to give 1,4-addition products
      selectively, unless the acceptor has a group stabilizing a radical intermediate,
      such as a phenyl group.

PMID- 10923835
TI  - Triterpenes from the spores of Ganoderma lucidum and their cytotoxicity against
      meth-A and LLC tumor cells.
AB  - Six new highly oxygenated lanostane-type triterpenes, called ganoderic acid gamma
      (1), ganoderic acid delta (2), ganoderic acid epsilon (3), ganoderic acid zeta
      (4), ganoderic acid eta (5) and ganoderic acid theta (6), were isolated from the
      spores of Ganoderma lucidum, together with known ganolucidic acid D (7) and
      ganoderic acid C2 (8). Their structures of the new triterpenes were determined as
      (23S)-7beta,15alpha,23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid
      (1), (23S)-7alpha,15alpha23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic
      acid (2), (23S)-3beta3,7beta, 23-trihydroxy-11,15-dioxolanosta-8,24(E)-diene-26
      oic acid (3), (23S)-3beta,23-dihydroxy-7,11,15-trioxolanosta-8, 24(E)-diene-26
      oic acid (4), (23S)-3beta,7beta,12beta,23-tetrahydroxy-11,15-dioxolanos ta
      8,24(E)-diene-26-oic acid (5) and (23S)-3beta,12beta23-trihydroxy-7,11,15
      trioxolanosta-8,24(E )-diene-26-oic acid (6), respectively, by chemical and
      spectroscopic means, which included the determination of a chiral center in the
      side chain by a modification of Mosher's method. The cytotoxicity of the
      compounds isolated from the Ganoderma spores was carried out in vitro against
      Meth-A and LLC tumor cell lines.

PMID- 10923836
TI  - In vivo evaluation of carborane gadolinium-DTPA complex as an MR imaging boron
      carrier.
AB  - The evaluation of the Gd-carborane complex 2 as an MR imaging and boron carrier
      agent was carried out in vivo using tumor-bearing Donryu rats, MRI, ICP-AES, and
      alpha-autoradiography. The MR imaging revealed that the carborane Gd-DTPA 2 was
      metabolized slower in the body than Gd-DTPA 1. The results of the ICP-AES method
      indicated that compound 2 was incorporated into normal tissues and metabolized
      quickly, whereas it was not accumulated into tumor or brain tissue. The alpha
      autoradiography showed that a high level of boron was obtained in the internal
      organs and in the necrosis of tumor tissue.

PMID- 10923837
TI  - Medicinal foodstuffs. XVIII. Phytoestrogens from the aerial part of Petroselinum
      crispum MIll. (Parsley) and structures of 6"-acetylapiin and a new monoterpene
      glycoside, petroside.
AB  - In the course of our screening for natural estrogenic compounds from Occidental
      medicinal herbs, the extracts of several herbs were found to show proliferative
      activity in MCF-7 (an estrogen-sensitive breast cancer cell line). Among these
      active herbs, the methanolic extract from the aerial parts of Petroselinum
      crispum (parsley) showed potent estrogenic activity, which was equal to that of
      isoflavone glycosides from soybean. Through bioassay-guided separation, we
      isolated several flavone glycosides and a new flavone glycoside, 6"-acetylapiin,
      with estrogenic activity together with a new monoterpene glucoside, petroside.
      The structures of 6"-acetylapiin and petroside were characterized by the chemical
      and physicochemical evidence. Estrogenic activities of these flavone glycosides
      were found to be enhanced by removal of their glycoside moieties. The EC50 values
      (concentration needed to enhance the MCF-7 proliferation 50% compared to non
      estrogen treated cell) of their aglycones are as follows, apigenin (1.0 microM),
      diosmetin (2.9 microM), and kaempferol (0.56 microM). The estrogenic activities
      of these flavones are nearly equal to those of the isoflavones, daidzein (0.61
      microM) and genistein (0.60 microM). The methanolic extract of parsley, apiin,
      and apigenin restored the uterus weight in ovariectomized mice when orally
      administered for consecutive 7 days.

PMID- 10923838
TI  - Bioactive saponins and glycosides. XVI. Nortriterpene oligoglycosides with
      gastroprotective activity from the fresh leaves of Euptelea polyandra Sieb. et
      Zucc. (1): structures of Eupteleasaponins I, II, III, IV, V, and V acetate.
AB  - The saponin fraction from the fresh leaves of Euiptelea polyandra Sieb. et Zucc.
      was found to exhibit potent gastroprotective activity. Fourteen new nortriterpene
      saponins called eupteleasaponins were isolated from the saponin fraction with
      gastroprotective activity. The structures of eupteleasaponins I, I1, III, IV, V,
      and V acetate were determined on the basis of chemical and physicochemical
      evidence as 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl(1 -->3)-beta
      D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L
      rhamnopyranosyl(1-->2)-[alpha-L-rhamnopyranosyl(1 -->4)-beta-D-glucopyranosyl(1-
      >3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D- D-glucopyranosyl(1-->3)-beta
      D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L
      rhamnopyranosyl(1-->2)-alpha-L-rhamnopyranosyl(1 -->4)-beta-D-glucopyranosyl(1-
      >3)-beta-D-xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O
      alpha-L-rhamnopyranosyl(1 -->2)-[alpha-L-arabinopyranosyl(1-->4)-alpha-L
      rhamnopyranosyl(1-- >4)]-beta-D- glucopyranosyl(1-->3)-beta-D
      xylopyranosylakebonoic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L
      rhamnopyranosvl(1-->2)-[alpha-L-arabinopyranosyl (1 -->4)-beta-L
      rhamnopyranosyl(1 -->4)]-beta-D-glucopyranosyl(1 -->3)-beta-D
      xylopyranosylakebonoic acid, 3-O-alpha-L-rhamnopyranosyl(1 -->2)-beta-D
      glucopyranosvl(1-->3)-beta-D-xylopyranosyleupteleo genin, and 3-O-alpha-L
      rhamnopyranosyl(1-->2)-6"-O-acetyl-gamma-D-glucopyranosyl(1 -->3)-beta-D
      xylopyranosyleupteleogenin.

PMID- 10923839
TI  - Chalcone and stilbene synthases expressed in eucaryotes exhibit reduced cross
      reactivity in vitro.
AB  - Chalcone synthase (CHS) and stilbene synthase (STS) catalyze different
      cyclization reactions of the common tetraketide to give different products,
      naringenin chalcone and resveratrol, respectively. We have previously observed in
      vitro cross-reaction of CHS and STS overexpressed in Escherichia coli,
      resveratrol production by CHS and chalcone production by STS. When expressed in
      eucaryotic cells, or in E. coli as thioredoxin-fusion proteins, CHS and STS
      exhibited reduced cross-reaction. STS refolded from inclusion bodies also showed
      reduced cross-reaction. While addition of bovine serum albumin and pH in the
      reaction were without noticeable effect, addition of glycerol decreased the cross
      reaction of CHS likely due to its stabilizing effect on enzyme conformation.
      These results were interpreted to provide supporting evidence to our earlier
      proposition (Yamaguchi T. et al., FEBS Lett., 460, 457-4 61 (1999)) that the in
      vitro cross-reaction of CHS and STS is due to intrinsic capability of these
      enzymes to catalyze different types of cyclization, which, in turn, is endowed by
      conformational flexibility of their active sites.

PMID- 10923840
TI  - Prolyl endopeptidase inhibitory activity of fourteen Kampo formulas and
      inhibitory constituents of Tokaku-joki-to.
AB  - Prolyl endopeptidase (PEP, EC 3.4.21.26) is an enzyme playing a role in the
      metabolism of proline-containing neuropeptides which have been suggested to be
      involved in learning and memory processes. In screening for PEP inhibitors from
      fourteen traditional Kampo formulas, we found that Tokaku-joki-to shows a
      significant inhibitory activity. Examination of the constituents of the Kampo
      formula resulted in the isolation of two new compounds, cis-3,5,4'
      trihydroxystilbene 4'-O-beta-D-(6-O-galloyl)glucopyranoside (10) and 4-(4
      hydroxyphenyl)-2-butanone 4'-O-beta-D-(6-O-galloyl-2-O-cinnamoyl)glucopyranoside
      (16), along with twenty-five known compounds, cinnamic acid (1), protocatechuic
      acid (2), gallic acid (3), torachrysone 8-O-beta-D-glucoside (4), emodin (5),
      emodin 8-O-beta-D-glucoside (6), 3,5,4'-trihydroxystilbene 4'-O-beta-D
      glucopyranoside (7), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(2-O
      galloyl)glucopyranoside (8), 3,5,4'-trihydroxystilbene 4'-O-beta-D-(6-O
      galloyl)glucopyranoside (9), 4-(4-hydroxyphenyl)-2-butanone 4'-O-beta-D
      glucopyranoside (11), isolindleyin (12), lindleyin (13), 4(4-hydroxyphenyl)-2
      butanone 4'-O-beta-D-(2,6-di-O-galloyl)glucopyranoside (14), 4-(4-hydroxyphenyl)
      2-butanone 4'-O-beta-D-(2-O-galloyl-6-O-cinnamoyl)glucopyranoside (15), 1-O
      galloylglucose (17), 1,2,6-tri-O-galloylglucose (18), gallic acid 4-O-beta-D-(6-O
      galloyl)glucopyranoside (19), liquiritigenin (20), liquiritigenin 4'-O-beta-D
      glucoside (21), liquiritigenin 7,4'-diglucoside (22), liquiritigenin 4'-O-beta-D
      apiofuranosyl-(1-->2)-beta-D-glucopyranoside (23), licuroside (24), (-)
      epicatechin (25), (-)-epicatechin 3-O-gallate (26) and (+)-catechin (27). Among
      these compounds, twelve (7-10, 14-16, 18, 19, 24-26) showed noncompetitive
      inhibition with an IC50 of 22.9, 3.0, 14.9, 2.8, 10.5, 0.69, 8.2, 0.44, 9.39,
      26.5, 28.1 and 0.052 microM, respectively.

PMID- 10923841
TI  - Steroidal oligoglycosides from Solanum nigrum.
AB  - Two new steroidal saponins, named nigrumnins I and II, together with two known
      saponins were obtained from the whole plant of Solanum nigrum L. On the basis of
      spectroscopic analysis (1H-NMR, 13C-NMR, 1H-1H COSY, TOCSY, HMQC, HMBC and FAB
      MS), nigrumnin I was established as (25R)-5alpha-spirostan-3beta-ol 3-O-betaD
      xylopyranosyl-(1-->3)-[alpha-L-arabinopyranosyl-(1 -->2)]-beta-D- glucopyranosyl
      (1-->4)-[alpha-L-rhamnopyranosyl(1-->2)]-beta-D- galactopyranoside (1), and
      nigrumnin II was elucidated as (25R)-3beta,17alpha-dihydroxy-5alpha-spirostan-1 2
      one 3-O-beta-D-xylopyranosyl-(1-->3)-[alpha-L-arabinopyranosyl-(1--> 2)]-beta-D
      glucopyranosyl-(1-->4)-[alpha-L-rhamnopyra- nosyl-(1-->2)l-beta-D
      galactopyranoside (2).

PMID- 10923842
TI  - Application of liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry to the differentiation of stereoisomeric diterpenoid alkaloids.
AB  - High-performance liquid chromatography-atmospheric pressure chemical ionization
      mass spectrometry (HPLC-APCI-MS) was successfully applied to seven stereoisomeric
      diterpenoid alkaloids at position 1 or 12. Comparison of the breakdown curves,
      observed by changing the potential difference between the first electrode and the
      second electrode of the APCI ion source, revealed stereochemical dependence of
      different fragmentations. The APCI spectra of alkaloids were predominantly the
      [M+H]+ ion and the major fragment ion, corresponding to the [M+H-H2O]+ ion or the
      [M+H-CH3COOH]+ ion, and comparison of the APCI spectra showed that the abundance
      of fragment ions was significantly higher for C-1 beta-form alkaloids than for C
      1 alpha-form alkaloids, and for C-12 beta-form alkaloids than for C-12 alpha-form
      alkaloids. The characteristic fragment ions were formed due to the loss of an
      acetic acid or a water molecule at position 12. The fragmentation mechanisms
      depending on the stereochemistry of the precursor ion could be discerned by
      recording the spectra in a deuterated solvent system of 0.05 M ammonium acetate
      in D2O-acetonitrile-tetrahydrofuran. Loss of CH3COOD or D2O from the precursor
      ion gave the fragment ion. This result indicated that the proton of protonation
      was included in the leaving acetic acid and water molecule, respectively. The
      peak intensity ratio for R=[M+H]+/[M+ H-H2O]+ + [M + H-CH3COOH] + manifested the
      stereochemical differentiation of alkaloids at position 1 or 12.

PMID- 10923843
TI  - Three new phenylethanoid glycosides from Caryopteris incana and their
      antioxidative activity.
AB  - Three new phenylethanoid glycosides, incanoside C, incanoside D and incanoside E
      were isolated together with one known glycoside, beta-D-fructofuranosyl-alpha-D
      (6-O-[E]-sinapoyl) glucopyranoside from the whole plant of Caryopteris incana
      (THUNB.) Miq. On the basis of chemical and spectral analyses, the structures of
      the new compounds were elucidated to be 1-O-(3,4-dihydroxyphenyl)ethyl-O-beta-D
      glucopyranosyl(1-->2)-alpha-L- rhamnopyranosyl(1-->3)-4-O-feruloyl-beta-D
      glucopyranoside (incanoside C), 1-O-(3-hydroxy-4-methoxyphenyl)ethyl-O-beta-D
      glucopyranosyl(1-->2)-alph a-L- rhamnopyranosyl(1-->3)-4-O-feruloyl-beta-D
      glucopyranoside (incanoside D) and 1-O-(3methoxy-4-hydroxyphenyl)ethyl-O-beta-D
      glucopyranosyl(1-->2) -alpha-L- rhamnopyranosyl(l-->3)-4-O-feruloyl-beta-D
      glucopyranoside (incanoside E). The three new phenylethanoid glycosides exhibited
      radical scavenging activities against DPPH radical and inhibitory activities
      against the oxidation of linoleic acid.

PMID- 10923844
TI  - A novel agarofuran sesquiterpene, celahin D from Celastrus hindsii Benth.
AB  - A novel agarofuran sesquiterpene polyol ester, 1beta,2beta,6alpha,15beta
      tetracetoxy-8 beta,9alpha-dibenzoyloxy-beta- dihydroagarofuran (celahin D) (1),
      two known analogues of 1,1beta-acetoxy-8beta,9alpha-dibenzoyloxy-4al pha6alpha
      dihydroxy-2beta(alphamethylbutanoyloxy)-beta-++ +dihydroagarofuran (2) and beta
      acetoxy-8beta,9alpha-dibenzoyloxy-6alpha-hy droxy-2beta(alpha -methylbutanoyloxy)
      beta-dihydroagarofuran (3), and a known cytotoxic sesquiterpene pyridine
      alkaloid, emarginatine E (4) were isolated from the stems of Celastrus hindsii
      Benth. Three known triterpenes, loranthol (5), lupenone (6) and friedelinol (7)
      were also obtained from the titled plant. Structural elucidation of compound 1
      was established by 2D NMR spectra.

PMID- 10923845
TI  - Macrophyllosaponin E: a novel compound from the roots of Astragalus. oleifolius.
AB  - Macrophyllosaponin E, a novel cycloartane-type triterpene, has been isolated from
      the roots of Astragalus oleifolius. The structure elucidation of the compound was
      achieved by a combination of one- and two-dimensional NMR techniques [1H-1H
      correlation spectroscopy (COSY), 1H-13C-heteronuclear multiple guantum
      correlation spectroscopy (HMQC), and 1H-13C-heteronuclear multiple-bond
      correlation spectroscopy (HMBC)l and high resolution electrospray ionization
      Fourier transformation mass spectrometry (HR-ESI-FT-MS).

PMID- 10923846
TI  - Isolation of lignan glucosides and neolignan sulfate from the leaves of
      Glochidion zeylanicum (Gaertn) A. Juss.
AB  - Six lignan and neolignan derivatives (1-6) were isolated from the n-BuOH-soluble
      fraction of a MeOH extract of the leaves of Glochidion zeylanicum. On the basis
      of spectral data, their structures were elucidated to be (+)-isolarisiresinol 3a
      O-beta-glucopyranoside (1), dihydrodehydrodiconiferyl alcohol 4-, 9- and 9'-O
      beta-D-glucopyranosides (2-4, respectively), (+)-isolarisiresinol 2a-O-beta-D
      glucopyranoside (5), and dihydrodehydrodiconiferyl alcohol 9-O-sulfate (6), and 5
      and 6 were new compounds.

PMID- 10923847
TI  - A new cytotoxic polyhydroxysterol from soft coral Sarcophyton trocheliophorum.
AB  - A new cytotoxic polyhydroxysterol, 23,24-dimethylcholest-16(17)-E-en
      3beta,5alpha,6beta,2 0(S)-tetraol (2), together with nine known compounds was
      isolated from the soft coral Sarcophyton trocheliophorum. Their structures were
      determined by spectroscopic methods. Compound 2 showed potent growth inhibitory
      activity against human HL60 leukemia, M14 skin melanoma, and MCF7 breast
      carcinoma cells with EC50 values of 2.8, 4.3, and 4.9 microg/ml, respectively,
      and exhibited minimal toxicity to normal human peripheral blood lymphocytes.

PMID- 10923848
TI  - Conduritol F glucosides and terpenoid glucosides from Cynanchum liukiuense and
      distribution of conduritol F glucosides in several Asclepiadaceous plants.
AB  - Conduritol F 3-0- and 4-O-glucosides were obtained from Cynanchum liukiuense,
      along with conduritol F which was identified in all Asclepiadaceous plants
      examined, Tylophora tanakae, Asclepias curassavica and A. fruticosa, as well as
      in Marsdenia tomentosa. The pattern of the glucosidic linkage to conduritol F
      differed between individual species, 2-O-glucoside from T tanakae and M.
      tomentosa, 3-O-glucoside from A. curassavica, but none from A. fruticosa. Along
      with conduritol F glucosides, an 11-glucosyloxy-megastigmane and a monoterpenoid
      glucoside were isolated from C. liukiuense.

PMID- 10923849
TI  - Antisweet natural products. XV. Structures of Jegosaponins A-D from Styrax
      japonica Sieb. et Zucc.
AB  - From the fresh fruits of Strrax japonica Sieb. et Zucc., four new triterpenoid
      glycosides, named jegosaponins A-D (1-4), were isolated. Their structures were
      determined on the basis of spectroscopic data and chemical evidence. Compounds 1
      4 are 3-O-tetraglycosides of barringtogenol C having an acetyl and a tigloyl or a
      (2Z)-hexenoyl groups at C-21, 22 and 28. The acylated saponins, 1-4, all showed
      antisweet activity.

PMID- 10923850
TI  - alpha,alpha-gem-Difluorination of alpha-(alkylthio)acetophenone derivatives with
      N-fluoropyridinium salts.
AB  - The alpha,alpha-gem-difluorination of 2',4'-difluoro-alpha
      (methylthio)acetophenone (1a) with N-fluoropyridinium salts gave
      2',4',alpha,alpha-tetrafluoro-alpha-(methylthio)acetophenone (3a). This reaction
      was accelerated by the addition of zinc chloride, zinc bromide or anhydrous
      iron(III) chloride, and higher yields than the reaction without additives were
      obtained. The gem-difluorination reaction using FP-T300 in the presence of zinc
      bromide was applicable to other alpha-(alkylthio)acetophenone derivatives (1).

PMID- 10923851
TI  - Geranylgeranyl diphosphate synthases from Scoparia dulcis and Croton sublyratus.
      cDNA cloning, functional expression, and conversion to a farnesyl diphosphate
      synthase.
AB  - cDNAs encoding geranylgeranyl diphosphate synthase (GGPPS) of two diterpene
      producing plants, Scoparia dulcis and Croton sublyratus, were isolated using the
      homology-based polymerase chain reaction method. Both cloned genes showed high
      amino acid sequence homology (60-70%) to other plant GGPPSs and contained highly
      conserved aspartate-rich motifs. The obtained clones were functionally expressed
      in Escherichia coli and showed sufficient GGPPS activity to catalyze the
      condensation of farnesyl diphosphate (FPP) and isopentenyl diphosphate to form
      geranylgeranyl diphosphate. To investigate the factor determining the product
      chain length of plant GGPPSs, S. dulcis GGPPS mutants in which either the small
      amino acids at the fourth and fifth positions before the first aspartate-rich
      motif (FARM) were replaced with aromatic amino acids or in which two additional
      amino acids in FARM were deleted were constructed. Both mutants behaved like FPPS
      like enzymes and almost exclusively produced FPP when dimethylallyl diphosphate
      was used as a primer substrate, and failed to accept FPP as a primer substrate.
      These results indicate that both small amino acids at the fourth and fifth
      positions before FARM and the amino acid insertion in FARM play essential roles
      in product length determination in plant GGPPSs.

PMID- 10923852
TI  - National HIV Testing Day at CDC-funded HIV counseling, testing, and referral
      sites--United States, 1994-1998.
AB  - CDC-funded human immunodeficiency virus (HIV) counseling, testing, and referral
      sites are an integral part of national HIV prevention efforts (1). Voluntary
      counseling, testing, and referral opportunities are offered to persons at risk
      for HIV infection at approximately 11,000 sites, including dedicated HIV
      counseling and testing sites, sexually transmitted disease (STD) clinics, drug
      treatment centers, hospitals, and prisons. Services also are offered to women in
      family planning and prenatal/obstetric clinics to increase HIV prevention efforts
      among women and decrease the risk for perinatal HIV transmission. To increase use
      of HIV counseling, testing, and referral services by those at risk for HIV
      infection, in 1995, the National Association of People with AIDS designated June
      27 each year as National HIV Testing Day. This report compares use of CDC-funded
      counseling, testing, and referral services the week before and the week of June
      27 from 1994 through 1998 and documents the importance of a national public
      health campaign designed to increase knowledge of HIV serostatus.

PMID- 10923853
TI  - Laboratory-acquired human glanders--Maryland, May 2000.
AB  - On May 5, 2000, the Baltimore City Health Department was notified by hospital
      infection-control staff of a serious systemic febrile illness in a microbiologist
      whose research at the U.S. Army Medical Research Institute of Infectious Diseases
      (USAMRIID) involved several pathogenic bacteria, including Burkholderia mallei,
      the causative agent of glanders. This report summarizes the first human case of
      glanders in the United States since 1945, and emphasizes the importance of
      considering occupational exposures among laboratory workers with a febrile
      illness, the difficulty of characterizing unusual agents, including potential
      agents of biological terrorism such as glanders using routine laboratory
      techniques, the appropriate isolation practices for patients who may be infected
      by these agents, and laboratory safety.

PMID- 10923854
TI  - Contribution of assisted reproductive technology and ovulation-inducing drugs to
      triplet and higher-order multiple births--United States, 1980-1997.
AB  - In the United States, pregnancies associated with assisted reproductive
      technology (ART) or ovulation-inducing drugs are more likely to result in
      multiple births than spontaneously conceived pregnancies (1). In addition,
      triplet and higher-order multiple births are at greater risk than singleton
      births to be preterm (< or = 37 completed weeks' gestation), low birthweight
      (LBW) (i.e., < or = 2500 g), or very low birthweight (i.e., < 1500 g), resulting
      in higher infant morbidity and mortality (2). Because preterm and LBW infants
      often require costly neonatal care and long-term developmental follow-up, the
      continuing increase in triplet and higher-order multiple births causes concern
      among health-care providers and policymakers (3). This report provides estimates
      of the contribution of ART and ovulation-inducing drugs to these birth outcomes
      for 1996 and 1997, and summarizes trends during 1980-1997, which indicate that
      the ratio of triplet and higher-order multiple births has more than quadrupled
      and that a large proportion of this increase can be attributed to ART or the use
      of ovulation-inducing drugs.

PMID- 10923855
TI  - Gonorrhea--United States, 1998.
AB  - Neisseria gonorrhoeae infections are a major cause of pelvic inflammatory
      disease, infertility, and ectopic pregnancy in women and facilitate the
      transmission of human immunodeficiency virus (1). To characterize the
      epidemiology of gonorrhea in the United States, CDC examined national
      surveillance data on gonorrhea cases reported to CDC through state health
      departments in 1998 and surveyed selected states with increases and decreases in
      gonorrhea rates since 1996. This report summarizes the results of this analysis,
      which indicate that following a 13-year decline, the number of gonorrhea cases in
      1998 increased by 9% compared with 1997. Although changes in gonorrhea screening
      and surveillance practices may have contributed to the higher reported rates,
      reports from states suggest that true increases in gonorrhea cases also occurred
      in some populations.

PMID- 10923856
TI  - Update: Clostridium novyi and unexplained illness among injecting-drug users-
      Scotland, Ireland, and England, April-June 2000.
AB  - Since April 19, 2000, health authorities in Scotland, Ireland, England, and the
      United States have been investigating an outbreak of unexplained illness and
      death among injecting-drug users (IDUs) in the United Kingdom and Ireland (1-3).
      Initial testing of specimens from 76 IDUs identified Clostridium species in 18
      (24%) patients; nine were Clostridium novyi. This report updates the
      investigation of this outbreak, which indicates that Clostridium species may be
      associated with these illnesses.

PMID- 10923857
TI  - Injuries from fireworks in the United States.
AB  - Fireworks traditionally are used in the United States to celebrate Independence
      Day on July 4th. The U.S. Consumer Product Safety Commission (CPSC) estimates
      that 8500 persons in the United States are treated in emergency departments each
      year for fireworks-related injuries (1). Of all fireworks-related injuries, 70%
      75% occur during a 30-day period that surrounds the July 4th holiday (June 23
      July 23) (2). Seven of every 100 persons injured by fireworks are hospitalized,
      approximately 40% of those injured are children aged < or = 14 years, and males
      are injured three times more often than females (1). The injury rate is highest
      among boys aged 10-14 years (3). Most commonly, injuries from fireworks affect
      the hands (34%), face (12%), and eyes (17%) (4). Injuries are more frequent and
      more severe among persons who are active participants than among bystanders (3).

PMID- 10923858
TI  - Regional and cellular distribution of CYP2D subfamily members in rat brain.
AB  - 1. Human CYP2D6 is present in brain, metabolizes many drugs and has been
      implicated in Parkinson's and Alzheimer's diseases and some cancers. It is still
      unclear which of the six known rat CYP2D subfamily members is/are homologous to
      human CYP2D6. 2. In this study, RT-PCR, Southern and Western blotting and
      immunohistochemical techniques were used to study the distribution of CYP2D
      subfamily member mRNA and proteins across 10 rat brain regions. CYP2D subfamily
      mRNA and protein levels were correlated with brain dextromethorphan O
      demethylation (DOD), a measure of human CYP2D6 and rat CYP2D1 activities. 3. The
      data showed a strong relationship between CYP2D1 and CYP2D1-18 with brain DOD
      activity. In addition, it was shown that CYP2D proteins are present in brain
      mitochondrial as well as microsomal membranes. CYP2D subfamily member mRNA and
      proteins varied across brain regions and were highly concentrated in specific
      cell types. 4. These data strongly suggest that CYP2D1 and not CYP2D5 mediates
      DOD activity in rat brain, and may be the rat homologue of human CYP2D6. The
      highly localized nature of CYP2D indicates that in specific neurones enzyme
      levels may approach hepatic levels and, hence, contribute to local alterations in
      brain drug metabolism.

PMID- 10923859
TI  - Identification of enzymes responsible for rifalazil metabolism in human liver
      microsomes.
AB  - 1. The major metabolites of rifalazil in human are 25-deacetyl-rifalazil and 32
      hydroxy-rifalazil. Biotransformation to these metabolites in pooled human liver
      microsomes, cytosol and supernatant 9000g (S9) fractions was studied, and the
      enzymes responsible for rifalazil metabolism were identified using inhibitors of
      esterases and cytochromes P450 (CYP). 2. The 25-deacetylation and 32
      hydroxylation of rifalazil occurred in incubations with microsomes or S9 but not
      with cytosol, indicating that both the enzymes responsible for rifalazil
      metabolism were microsomal. Km and Vmax of the rifalazil-25-deacetylation in
      microsomes were 6.5 microM and 11.9 pmol/min/mg with NADPH, and 2.6 microM and
      6.0 pmol/min/mg without NADPH, indicating that, although rifalazil-25
      deacetylation did not require NADPH, NADPH activated it. Rifalazil-32
      hydroxylation was NADPH dependent, and its Km and Vmax were 3.3 microM and 11.0
      pmol/min/mg respectively. 3. Rifalazil-25-deacetylation in microsomes was
      completely inhibited by diisopropyl fluorophosphate, diethyl p-nitrophenyl
      phosphate and eserine, but not by p-chloromercuribenzoate or 5,5'-dithio-bis(2
      nitrobenzoic acid), indicating that the enzyme responsible for the rifalazil-25
      deacetylation is a B-esterase. 4. Rifalazil-32-hydroxylation in microsomes was
      completely inhibited by CYP3A4-specific inhibitors (fluconazole, ketoconazole,
      miconazole, troleandomycin) and drugs metabolized by CYP3A4 such as cyclosporin A
      and clarithromycin, indicating that the enzyme responsible for the rifalazil-32
      hydroxylation is CYP3A4.

PMID- 10923861
TI  - Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of
      human hepatocytes: a 10-year follow-up.
AB  - 1. The aims were to refine experimental conditions (using 76 human hepatocyte
      preparations) in terms of the selection of enzyme inducers and their optimal
      concentration, the treatment duration with inducers and the choice of specific
      cytochrome P450 isoform(s) probes to optimize the use of primary hepatocytes for
      predicting the potential induction by new chemical entities of cytochrome P450
      isoforms in vivo in man. 2. In the absence of any inducer, basal cytochrome P450
      isoform(s)-mediated activities decreased to 20% of their initial activity (end of
      the seeding period) by 72-96 h. In contrast, UGT-dependent enzyme activities
      remained at a constant level (+/- 20%) up to the fifth day of culture. 3. Beta
      naphthoflavone, at an optimal concentration of 50 microM and after a 3-day
      treatment, specifically and potently induced 7-ethoxyresorufin (10.4 +/- 10.4
      fold, n = 74) and phenacetin (6.6 +/- 6.4-fold, n = 60) O-deethylation processes,
      markers for CYP1A1 and CYP1A2 isoforms respectively. Only a 2-fold increase was
      noted following treatment with 2 mM phenobarbitone, whereas dexamethasone and
      rifampicin had no effect at all. 4. A 3-day treatment of human hepatocytes with
      50 microM dexamethasone was associated with a major induction of both coumarin 7
      hydroxylation (9.4 +/- 11.4-fold, n = 49) and nifedipine dehydrogenation (4.7 +/-
      3.8-fold, n = 61), markers for CYP2A6 and CYP3A4 respectively. Phenobarbitone,
      however, exhibited a broad but moderate inducing effect on 7-ethoxyresorufin (2.2
      +/- 1.5-fold, n = 55) and phenacetin (1.7 +/- 0.9-fold, n = 54) O-deethylation,
      coumarin 7-hydroxylation (3.9 +/- 9.2-fold, n = 50) and nifedipine
      dehydrogenation (2.1 +/- 2.0-fold, n = 47). 5. Km obtained for the different
      cytochrome P450 isoform substrates in untreated hepatocytes were in the same
      range of magnitude that those determined on human hepatic microsomal fractions.
      Enzyme induction processes were characterized by a large increase in apparent
      Vmax whereas apparent Km were not affected. 6. These studies demonstrate that
      human hepatocytes in primary culture can respond specifically and quantitatively
      to model inducers. This in vitro system offers a useful approach to study the
      regulation of human hepatic biotransformation activities and should facilitate
      the demand for a reproducible method for addressing cytochrome P450 induction.

PMID- 10923860
TI  - Evidence for propofol hydroxylation by cytochrome P4502B11 in canine liver
      microsomes: breed and gender differences.
AB  - 1. The study aimed to ascertain the enzyme kinetic basis for breed differences in
      the biotransformation of propofol in dog and to identify the responsible canine
      cytochrome P450 (CYP) isoenzymes. 2. The NADPH-dependent formation of 4
      hydroxypropofol (the rate-limiting biotransformation in dog) was assayed using
      hepatic microsomes from the male greyhound and beagle, and from both sexes in
      mixed-breed dogs (five of each). 3. Enzyme kinetic analysis revealed that whereas
      there were no significant differences in Km, Vmax averaged > 3-fold lower in
      greyhound compared with beagle (p = 0.032). Although average Vmax was > 3-fold
      higher in the male compared with female mixed-breed dogs, this difference did not
      achieve statistical significance (p = 0.095), probably because of the high
      variability of data from mixed-breed dogs. 4. Chloramphenicol (a specific CYP2B11
      inhibitor) and diethyldithiocarbamate (a non-specific CYP2 inhibitor) inhibited
      propofol hydroxylation in all microsomes. Quinine (a CYP2D15 inhibitor) was also
      inhibitory, but only in one-half of the microsomes examined. Immuno-inhibition by
      anti-CYP2B1 sera resulted in > 50% reduction in metabolite formation in all dogs
      except mixed-breed females, which showed a 30% reduction. Differences in propofol
      hydroxylase activity between microsomal preparations were primarily attributed to
      a component that was sensitive to inhibition by chloramphenicol and anti-CYP2B1
      sera. 5. The results indicate that propofol hydroxylation in dog is primarily
      mediated by CYP2B11 and that breed (and possibly gender) differences in propofol
      metabolism may result from differences in the liver content of this CYP.

PMID- 10923862
TI  - Sulphation of resveratrol, a natural product present in grapes and wine, in the
      human liver and duodenum.
AB  - 1. Resveratrol, a polyphenolic compound present in grapes and wine, has
      beneficial effects against cancer and protective effects on the cardiovascular
      system. It is present in the diet, and the hepatic and duodenal sulphation might
      limit the bioavailability of this compound. The aim was to study the sulphation
      of resveratrol in the human liver and duodenum. 2. A simple and reproducible
      radiometric assay for resveratrol sulphation was developed. It employed 3'
      phosphoadenosine-5'-phosphosulphate-[35S] as the sulphate donor and the rates of
      resveratrol sulphation (mean +/- SD, pmol/min/mg cytosolic protein) were 90 +/-
      21 (liver, n = 10) and 74 +/- 60 (duodenum, n = 10, p = 0.082). 3. Resveratrol
      sulphotransferase followed Michaelis-Menten kinetics and Km (mean +/- SD; microM)
      was 0.63 +/- 0.03 (liver, n = 5) and 0.50 +/- 0.26 (duodenum, n = 5, p = 0.39)
      and Vmax (mean +/- SD, pmol/min/mg cytosolic protein) were 125 +/- 31 (liver, n =
      5) and 129 +/- 85 (duodenum, n = 5, p = 0.62). 4. Resveratrol sulphation was
      inhibited by the flavonoid quercetin, by mefenamic acid and salicylic acid, two
      commonly used non-steroidal anti-inflammatory drugs. IC50 of resveratrol
      sulphation for quercetin was 12 +/- 2 pM (liver) and 15 +/- 2 pM (duodenum),
      those for mefenamic acid were 24 +/- 3 nM (liver) and 11 +/- 0.6 nM (duodenum),
      and those for salicylic acid were 53 +/- 9 microM (liver) and 66 +/- 4 microM
      (duodenum). 5. The potent inhibition of resveratrol sulphation by quercetin, a
      flavonoid present in wine, fruits and vegetables, suggests that compounds present
      in the diet may inhibit the sulphation of resveratrol, thus improving its
      bioavailability.

PMID- 10923863
TI  - An inhibitory monoclonal antibody to human cytochrome P450 that specifically
      binds and inhibits P4502C9II, an allelic variant of P4502C9 having a single amino
      acid change Arg144 Cys.
AB  - A monoclonal antibody (MAb 292-2-3) has been isolated that binds specifically to
      a single allele of three expressed human cytochrome P4502C9 alleles. The MAb
      binds to 2C9Cys144 (II), and does not bind to the wild-type 2C9Arg144 (I), or the
      third allele 2C9Ile-->Leu359 (III) and thus the MAb detects an allele with > 99%
      homology and differing from the wild-type 2C9Arg144 (I) by a single amino acid.
      The MAb 292-2-3 does not bind to the other 2C isoforms (2C8, 2C18, 2C19) or the
      other human cytochrome P450s, 1A1, 1A2, 2A6, 2B6, 2C8, 2D6, 2E1 or 3A4/5. MAb 292
      2-3 inhibits the metabolism of tolbutamide, diclofenac and phenanthrene by the
      target 2C9Cys144 (II) allele by > 90% and does not inhibit the catalytic activity
      of the wild-type 2C9Arg144 (I), or 2C9Ile-->Leu359 (III) the other 2C isoforms
      2C8, 2C18, 2C19, or the other non-2C human P450s listed above. The MAb 292-2-3 is
      thus a prototype of an ideal and extraordinarily specific reagent for the
      detection and measurement of the metabolic role of highly related isoforms and
      polymorphic alleles of human cytochrome P450s. MAbs of high specificity can also
      determine the amount of phenotypic expression of polymorphic alleles and their
      metabolic role in drug and non-drug xenobiotic metabolism in heterozygote
      individuals. The inhibitory MAb might also identify allele-specific substrates of
      polymorphic human cytochrome P450s.

PMID- 10923864
TI  - Pharmacokinetics and metabolism of a sulphamide NK2 antagonist in rat, dog and
      human.
AB  - 1. UK-224,671 is a sulphamide-containing NK2 antagonist with moderate
      lipophilicity and basicity. 2. The physicochemical properties of UK-224,671 are
      reflected in its pharmacokinetics following intravenous (i.v.) administration.
      The compound partitioned extensively into red blood cells in all species examined
      and the blood clearance was moderate to low with respect to liver blood flow and
      distribution into tissues was extensive. 3. UK-224,671 exhibited species
      differences in oral bioavailability. In dog, the compound exhibited moderate
      bioavailability (55%), whereas in rat and man oral bioavailability was < 10%. 4.
      In rat and dog, the major excreted form after i.v. administration was unchanged
      UK-224,671 in both urine and faeces. In addition, of three metabolites observed,
      the most abundant was the N-descyclopropylmethyl (UK-280,045). 5. The profile of
      radioactivity in rat following oral administration of [14C]-UK-224,671 was not
      consistent with a 10% absorbed compound with 40% of the dose present as
      metabolites. This suggests that the low bioavailability of UK-224,671 in rat is
      due to a combination of moderate intestinal permeability and extensive first-pass
      metabolism by the gut and does not result from poor gastrointestinal absorption
      per se.

PMID- 10923865
TI  - Metabolism of a novel hypnotic, N3-phenacyluridine, and hypnotic and sedative
      activities of its enantiomer metabolites in mouse.
AB  - 1. The metabolism of N3-phenacyluridine (3-phenacyl-1-beta-D
      ribofuranosyluracil), a potent hypnotic nucleoside derivative, was studied in
      mouse. 2. Of the radioactivity, 65% was excreted in urine within 48 h after
      intraperitoneal (i.p.) administration of [3H]N3-phenacyluridine. The urinary
      metabolites N3-phenacyluracil and N3-alpha-hydroxy-beta-phenethyluridine were
      extracted, isolated and analyzed by mass spectrometry. 3. Racemates of N3-alpha
      hydroxy-beta-phenethyluridine were synthesized and both isomers were separated as
      N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine and N3-(R)-(-)-alpha-hydroxy-beta
      phenethyluridine by hplc (CHIRALCEL-OJ column) with retentions of 13.8 and 17.9
      min respectively. The reduction process took place with high stereo-selectivity,
      which gave an alcohol product in the urine with the same retention (17.9 min) as
      one of the synthetic isomers separated by hplc. 4. One of urinary metabolites was
      identified as N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine. N3-phenacyluridine
      was predominantly converted to an alcoholic metabolite of (S)-(+)-configuration.
      5. N3-phenacyluracil and uridine were also identified as minor metabolites. 6.
      The pharmacological effects of the metabolites and related compounds were also
      evaluated in mouse. N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not N3
      (R)-(-)-alpha-hydroxy-beta-phenethyluridine, possessed hypnotic activity and
      potentiated pentobarbital-induced sleeping time with a similar potency to the
      parent compound, N3-phenacyluridine. N3-alpha-hydroxy-beta-phenethyluridine
      (racemate) had almost two thirds of the hypnotic activity of N3-(S)-(+)-alpha
      hydroxy-beta-phenethyluridine. No other metabolites exhibited hypnotic
      activities. 7. The present study indicates that N3-(S)-(+)-alpha-hydroxy-beta
      phenethyluridine, a major metabolite of N3-phenacyluridine, is an active
      metabolite and contributes a significant CNS depressant effect.

PMID- 10923866
TI  - The wave bivector formalism associated with circumferential leaky waves
AB  - It is shown that the circumferential internal waves propagating around an elastic
      cylinder can be locally seen as plane evanescent waves, at any observation point
      inside the surrounding fluid. This is done by direct calculation of the
      associated complex bivector. The exact anatomy of the wave is detailed and the
      phase propagation paths are found to be curved, as expected. The transition to
      the plane interface is achieved. Polarization ellipses associated with the
      acoustic displacement vector are described. The additional low evanescence
      assumption leads to conventional ray interpretation with identification of the
      ray tube divergence coefficients, and the wavefront is found to be the involute
      of a circle.

PMID- 10923867
TI  - A fast method for acoustic imaging of multiple three-dimensional objects.
AB  - This paper is concerned with the inverse problem for imaging multiple three
      dimensional objects using the information of the far-field pattern of the
      scattered wave. A spatially dependent function, which has noticeably different
      values inside and outside the obstacle, is derived. A numerical method based on
      the characterization is developed to obtain a visualization of the obstacle. The
      most remarkable advantage of this method is that it does not need any prior
      knowledge about the geometry and physical properties of the scatterer, and
      requires only the information of the far-field measurements for a finite number
      of directions of incidence and observation distributed over a limited range.
      Furthermore, the scheme is very simple and fast since it avoids the use of the
      iterative procedure and requires only the solution of a linear system. Some
      numerical examples with synthetic far-field data are given showing the
      practicality and efficiency of this scheme.

PMID- 10923868
TI  - Exact solutions to one-dimensional acoustic fields with temperature gradient and
      mean flow.
AB  - An exact solution for one-dimensional acoustic fields in ducts in the presence of
      an axial mean temperature gradient and mean flow is presented in this paper. The
      analysis is valid for mean Mach numbers such that the square of the mean Mach
      number is much less than one. The one-dimensional wave equation for ducts with
      axial mean temperature gradient and mean flow is derived. By appropriate
      transformations, the wave equation is reduced to an analytically solvable
      hypergeometric differential equation for the case of a linear mean temperature
      profile. The developed solution is applied to investigate the dependence of sound
      propagation in a duct on factors such as temperature gradient and mean flow. The
      results obtained using the analytical solution compare very well with the
      numerical results. The developed solution is also compared with an existing
      analytical solution.

PMID- 10923869
TI  - A rapid technique to determine the internal area function of finite-length ducts
      using maximum length sequence analysis
AB  - This paper describes a rapid technique for reconstruction of the internal area
      function of a duct using blockage-induced eigenvalue shifts determined from
      eigenfrequencies measured under two sets of duct termination boundary conditions.
      A single broad band maximum length sequence (MLS) measurement of short duration
      is utilized to obtain the transfer function of the duct, which in turn can be
      utilized to determine its eigenvalue shifts and subsequently its internal area
      function using an inverse perturbation technique. The reconstruction results
      display the same order of accuracy as those obtained previously using swept sine
      measurements of extended duration. An expression for the determination of the
      area function is presented utilizing resonant frequency information alone, thus
      rendering duct length determination unnecessary. A computational routine further
      simplifies the process such that the accuracy of the technique could be
      ascertained for a range of configurations including longer ducts and ducts that
      initially have nonuniform internal cross section over their length. Development
      of a relationship between obstacle length and wavelength of the lowest
      eigenfrequency required for successful reconstruction is also described. This is
      an important result for longer ducts where measurement of lower eigenfrequencies
      may present problems using standard measurement equipment.

PMID- 10923870
TI  - Simulation of stress waves in attenuating drill strings, including piezoelectric
      sources and sensors
AB  - A key element in drill steering and prediction of lithology ahead-of-the-bit is
      the transmission of while-drilling information from the bottom of the well to the
      rig operator and the geophysicists. Mud-pulse telemetry, based on pressure pulses
      along the drilling mud and extensional waves through the drill string, is the
      most used technique. The last method, properly designed, could transmit data
      rates up to 100 bits per second, against the 1 or 2 bits per second achieved with
      pressure pulses. In this work, a time-domain algorithm is developed for the
      propagation of one-dimensional axial, torsional, and flexural stress waves,
      including transducer sources and sensors. In addition, the equations include
      relaxation mechanisms simulating the viscoelastic behavior of the steel,
      dielectric losses, and any other losses, such as those produced by the presence
      of the drilling mud, the casing, and the formation. Moreover, the algorithm
      simulates the passbands and stopbands due to the presence of the coupling joints
      and pulse distortion and delay due to nonuniform cross-section areas. Acoustic
      and electric pulses, generated at one location in the string, can be propagated
      and detected at any other location by piezoelectric and acoustic sensors, such as
      PCB accelerometers, clamp-on ammeters, force, and strain transducers.

PMID- 10923871
TI  - Calculation of B/A for n-alkane liquids using the Tait equation
AB  - The B/A parameter of acoustic nonlinearity was calculated for a series of n
      alkane liquids using the Tait PVT equation of state supplemented with specific
      heat data. The calculations of sound speed, sound speed derivatives, the two
      components of B/A, and the value of B/A itself were compared with experimental
      data taken from the literature and with earlier calculations using a different
      equation of state. In addition, a comparison of the results with Ballou's rule
      (linear relation of B/A and reciprocal sound speed) was made. It is concluded
      that B/A can be calculated from the Tait equation of state with about the same
      accuracy as direct measurements of sound speed versus pressure and temperature,
      though the the temperature derivatives of the sound speed are calculated with
      much lower accuracy than pressure derivatives. The calculations made using the
      Tait equation are about the same accuracy as calculations made using our equation
      of state. Also, Ballou's rule does not hold for these liquids.

PMID- 10923872
TI  - The scaling of the wall pressure fluctuations in polymer-modified turbulent
      boundary layer flow
AB  - Wall pressure fluctuations and integrated skin friction were measured beneath a
      turbulent boundary layer that was modified by adding drag-reducing polymer to the
      pure water flow. The measurements were performed on an axisymmetric model,
      equipped with an isolated cylindrical drag balance section, and placed in the
      test section of the 0.3048-m-diam water tunnel at ARL Penn State. Data were
      acquired at a free-stream velocity of 10.7 m/s with pure water and with polymer
      added to the water at concentrations of 1, 5, 10, and 20 weight parts per
      million. Nondimensionalization of the wall pressure fluctuation frequency spectra
      with traditional outer, inner, and mixed flow variables failed to adequately
      collapse the data. The mean square wall pressure fluctuations were found to scale
      linearly with the wall shear stress. Polymer addition had little effect on the
      characteristic time scale of the flow. These properties were used to develop a
      novel form of the nondimensional wall pressure fluctuation spectrum that provided
      the best collapse of the measured data.

PMID- 10923873
TI  - Coupled mode perturbation theory of range dependence
AB  - The conventional coupled mode solution is combined with perturbation theory to
      give a fast, accurate range-dependent normal mode solution for deep water
      acoustic propagation. Perturbation theory is used to calculate the new normal
      modes at each range step. The new modes are obtained as a linear combination of
      the modes for the previous step without requiring a numerical solution of the
      depth-separated wave equation. The process may be repeated for many steps and
      yields normal modes and eigenvalues which are sufficiently accurate for solution
      of practical problems in deep water. The method is applied to long-range
      propagation through oceanic fronts.

PMID- 10923874
TI  - Manifestation of ray stochastic behavior in a modal structure of the wave field
AB  - A ray-based mathematical formalism is described to analyze modal structure
      variations in a range-dependent wave guide. In the scope of this formalism mode
      amplitudes are expressed through parameters of ray trajectories. Therefore, the
      approach under consideration provides a convenient tool to study how chaotic ray
      motion manifests itself in an irregular range dependence of the modal structure.
      The phenomenon of nonlinear ray-medium resonance playing a crucial role in the
      emergence of ray chaos has been interpreted from the viewpoint of normal modes.
      It has been shown that in terms of modes the coexistence of regular and chaotic
      rays means the presence of regular and irregular constituents of mode amplitudes.
      An analog to incoherent summation of rays has been proposed to evaluate mode
      intensities (squared mode amplitudes) smoothed over the mode number. Numerical
      calculations have shown that it gives correct results for smoothed mode
      intensities at surprisingly long ranges.

PMID- 10923875
TI  - Acoustically derived ice-fracture velocity in central Arctic pack ice.
AB  - Sounds radiated by fractures in Arctic ice (called acoustic events) are used to
      estimate fracture velocity. Both speed and orientation are obtained by measuring
      Doppler shifts induced by source motion. Data from the SIMI experiment of 1994 in
      the central Arctic are used in the frequency window 10 to 350 Hz. The estimation
      procedure assumes that each fracture propagates unilaterally, i.e.,
      unidirectionally. Results for a population of 186 events show fracture
      propagation speed to be mostly subsonic, in the range 100 to 1100 m/s,
      significantly lower than the Rayleigh wave speed (1700 m/s for sea ice) assumed
      in previous studies. The wide range of speeds observed indicates either the
      presence of distinct multiple fractures in each event, or of a single mechanism
      at different stages in its propagation.

PMID- 10923876
TI  - Tomography of dispersive media
AB  - When waves propagate through layered structures, the phase velocity is frequency
      dependent (dispersive). If one wants to reconstruct the velocity variations in
      this medium, conventional traveltime-based tomographic methods cannot be used,
      since each frequency component has a different traveltime. A tomographic method
      is presented for reconstructing the phase velocity of guided waves in laterally
      varying media. The dispersive character of guided waves is explicitly accounted
      for by using a phase-based error criterium instead of "picked" traveltimes. Phase
      velocity and source waveform can be reconstructed to within a few percent, and
      the algorithm is shown to be robust in the presence of interference noise. When
      applied to seismic field data, the reconstructed phase velocity field correlates
      well with the topography of the area.

PMID- 10923877
TI  - Experimental study of the liquid flow near a single sonoluminescent bubble
AB  - Tracers (sulphur particles produced in situ by a bubble itself, fuchsin spots and
      dust) were used to probe the liquid flows in the neighborhood of single
      sonoluminescent bubbles maintained in levitation in a resonant acoustic setup.
      The flows caused by the bubble were distinguished clearly from the streamings
      (mean Lagrangian velocity: approximately 20 microm/s) associated with resonant
      cells in the absence of a bubble. The liquid flow due to the presence of the
      bubble formed around it over a few mm. The radial component of the Lagrangian
      velocities (maximum value measured: approximately 260 microm/s) of this flow
      evolved as r(-1) , with r as the distance from the bubble, while the tangential
      component remained approximately constant (approximately 20 microm/s). In the
      Appendix by M. S. Longuet-Higgins, a simplified model of microstreaming involving
      a spherical bubble in translational and radial oscillation gives a qualitative
      description of the experiments. A fairly good agreement was observed between the
      experiments and the modeling, which involved a dipole flow enclosed in a
      Stokeslet.

PMID- 10923878
TI  - Attenuation and dispersion of sound in dilute suspensions of spherical particles
AB  - This paper considers sound propagation in dilute suspensions of constant-mass
      particles that can translate and pulsate under the effects of a small amplitude
      sound wave. A new theory for sound attenuation and dispersion is developed on the
      basis of the changes of the suspension's compressibility produced by the relative
      motions between host fluid and particles. The approach, used earlier to treat
      propagation in rigid-particle suspensions, decouples the propagation problem from
      the more difficult problem of obtaining accurate descriptions for the fluid
      particle interactions. In this work the role of the pulsational motion is
      included in the theoretical framework. The resulting theory is thus applicable to
      aerosols, bubbly liquids, emulsions, and hydrosols composed of elastic particles,
      and includes, as a special limit, rigid-particle suspensions. The results are
      expressed in terms of three complex quantities that describe, respectively, the
      particles' translational velocity, temperature, and pressure, relative to their
      counterparts in the fluid. Theoretical results for these quantities, applicable
      in wide frequency ranges, are available from previous studies [Temkin and Leung,
      J. Sound Vib. 49, 75-92 (1976), Temkin, J. Fluid. Mech. 380, 1-38 (1999)].
      Together with the compressibility theory presented here, they provide a more
      general description of propagation in dilute suspensions than presently
      available. In the case of aerosols and hydrosols, the theory produces known
      results for the attenuation and the sound speed. For bubbly liquids and emulsions
      the new results presented here differ from those available in the literature. The
      differences are traced to the neglect in the existing theories of the acoustic
      pressure disturbance produced by the pulsations of the particles.

PMID- 10923879
TI  - Acoustic imaging of objects buried in soil.
AB  - In this study, we demonstrate an acoustic system for high-resolution imaging of
      objects buried in soil. Our goal is to image cultural artifacts in order to
      assess in a rapid manner the historical significance of a potential construction
      site. We describe the imaging system and present preliminary images produced from
      data collected from a soil phantom. A mathematical model and associated computer
      software are developed in order to simulate the signals acquired by the system.
      We have built the imaging system, which incorporates a single element source
      transducer and a receiver array. The source and receiver array are moved together
      along a linear path to collect data. Using this system, we have obtained B-mode
      images of several targets by using delay-and-sum beamforming, and we have also
      applied synthetic aperture theory to this problem.

PMID- 10923880
TI  - Transient interaction of parallel thin-walled cylindrical piezoelectric ceramic
      radiators
AB  - This paper includes formulation of the multiconnected transient problem for an
      underwater transducer system of two thin-walled cylindrical piezoelectric ceramic
      radiators, description of an analytical method of solution, and investigation of
      fundamental regularities of transient processes. All these points take into
      account the interaction of reflectors. Radiators with continuous and sectioned
      electrodes are considered during excitation with different electrical impulses.
      An experimental test of selected mathematical models has been done.

PMID- 10923881
TI  - Determination of the dynamic elastic moduli and internal friction using thin
      resonant bars
AB  - Analysis of the data from the resonant-bar technique for determining wave speed
      and internal friction is presented. Internal friction has been included in the
      longitudinal and torsional wave equations and the analytical solution has been
      obtained. In determining the acoustical constants of lossy materials, a broad
      frequency spectrum is used that includes many resonances and not just data at or
      near the individual resonances. Corrections due to the mass, length, stiffness,
      and damping of the transducers are also presented. The theoretical solutions are
      compared with the measured magnitude and phase response data for torsional,
      longitudinal, and flexural measurements and are shown to be in good agreement.

PMID- 10923882
TI  - A strip-element method for analyzing wave scattering by a crack in an immersed
      axisymmetric laminated composite cylinder
AB  - A strip-element method is presented for analyzing wave scattering by a crack in a
      laminated composite cylinder immersed in a fluid. In this approach, two-nodal
      line and three-nodal-line axisymmetric strip elements are employed to model the
      fluid and laminated cylinder, respectively. Governing equations for the fluid and
      solid elements in the frequency domain are derived with a variational method and
      the Hamilton principle. The associated characteristic equations in the wave
      number domain are obtained through Fourier transform techniques. Responses of the
      fluid-loaded cylinder to a line load are found by a modal-analysis method and
      inverse Fourier transform techniques. Numerical results are presented for cracked
      laminated composite cylinders submerged in water. Water is found to have strong
      influence on the scattered wave fields in a cracked laminated composite cylinder.

PMID- 10923883
TI  - Dissipation in solids: thermal oscillations of atoms
AB  - Dissipation in solids describes conversion of kinetic energy to thermal energy.
      Heat capacity of a solid relates to the kinetic energy of the oscillations of its
      atoms with the assumption that they are in thermal equilibrium. Previous studies
      investigated criteria related to thermal relaxation, the process by which thermal
      equilibrium is established. They examined conditions for irreversible
      distribution of energy among the modes of a nonlinear periodic structure that
      represents atoms in a solid. These studies all point to the chaotic behavior of a
      freely vibrating nonlinear lattice as the kernel of the problem in addressing
      thermal relaxation. This paper extends the results of previous studies on
      thermalization to modeling of dissipation as energy absorption that takes place
      during forced vibration of particles in a nonlinear lattice. Results show that
      dissipation and chaotic behavior of the particles develop simultaneously. Such
      behavior develops when the forcing frequency falls within a resonance band. The
      results also support the argument that for a real solid, both in terms of size
      and complexity, resonance bands overlap significantly broadening the frequency
      range within which dissipation takes place.

PMID- 10923884
TI  - Narrowband and broadband active control in an enclosure using the acoustic energy
      density
AB  - An active control system based on the acoustic energy density is investigated.
      The system is targeted for use in three-dimensional enclosures, such as aircraft
      cabins and rooms. The acoustic energy density control method senses both the
      potential and kinetic energy densities, while the most popular control systems of
      the past have relied on the potential energy density alone. Energy density fields
      are more uniform than squared pressure fields, and therefore, energy density
      measurements are less sensitive to sensor location. Experimental results are
      compared to computer-generated results for control systems based on energy
      density and squared pressure for a rectangular enclosure measuring 1.5 x 2.4 x
      1.9 m. Broadband and narrowband frequency pressure fields in the room are
      controlled experimentally. Pressure-field and mode-amplitude data are presented
      for the narrowband experiments, while spectra and pressure-field data are
      presented for the broadband experiment. It is found that the energy density
      control system has superior performance to the squared pressure control system
      since the energy density measurement is more capable of observing the modes of a
      pressure field. Up to 14.4 and 3.8 dB of cancellation are achieved for the energy
      density control method for the narrowband and broadband experiments presented,
      respectively.

PMID- 10923885
TI  - The coherence of reverberant sound fields.
AB  - A new method of measuring spatial correlation functions in reverberant sound
      fields is presented. It is shown that coherence functions determined with
      appropriate spectral resolution contain the same information as the corresponding
      correlation functions, and that measuring such coherence functions is a far more
      efficient way of obtaining this information. The technique is then used to verify
      theoretical predictions of the spatial correlation between various components of
      the particle velocity in a diffuse sound field. Other possible applications of
      the technique are discussed and illustrated with experimental results obtained in
      an ordinary room.

PMID- 10923886
TI  - Error analysis of a practical energy density sensor
AB  - The investigation of an active control system based on acoustic energy density
      has led to the analysis and development of an inexpensive three-axes energy
      density sensor. The energy density sensor comprises six electret microphones
      mounted on the surface of a 0.025-m (1 in.) radius sphere. The bias errors for
      the potential, kinetic, and total energy density as well as the magnitude of
      intensity of a spherical sensor are compared to a sensor comprising six
      microphones suspended in space. Analytical, computer-modeled, and experimental
      data are presented for both sensor configurations in the case of traveling and
      standing wave fields, for an arbitrary incidence angle. It is shown that the
      energy density measurement is the most nearly accurate measurement of the four
      for the conditions presented. Experimentally, it is found that the spherical
      energy density sensor is within +/- 1.75 dB compared to reference measurements in
      the 110-400 Hz frequency range in a reverberant enclosure. The diffraction
      effects from the hard sphere enable the sensor to be made more compact by a
      factor of 3 compared to the sensor with suspended microphones.

PMID- 10923887
TI  - Time reversal and the inverse filter.
AB  - To focus ultrasonic waves in an unknown inhomogeneous medium using a phased
      array, one has to calculate the optimal set of signals to be applied on the
      transducers of the array. In the case of time-reversal mirrors, one assumes that
      a source is available at the focus, providing the Green's function of this point.
      In this paper, the robustness of this time-reversal method is investigated when
      loss of information breaks the time-reversal invariance. It arises in dissipative
      media or when the field radiated by the source is not entirely measured by the
      limited aperture of a time-reversal mirror. However, in both cases, linearity and
      reciprocity relations ensure time reversal to achieve a spatiotemporal matched
      filtering. Nevertheless, though it provides robustness to this method, no
      constraints are imposed on the field out of the focus and sidelobes may appear.
      Another approach consists of measuring the Green's functions associated to the
      focus but also to neighboring points. Thus, the whole information characterizing
      the medium is known and the inverse source problem can be solved. A matrix
      formalism of the propagation operator is introduced to compare the time-reversal
      and inverse filter techniques. Moreover, experiments investigated in various
      media are presented to illustrate this comparison.

PMID- 10923888
TI  - Complex tone processing in primary auditory cortex of the awake monkey. I. Neural
      ensemble correlates of roughness.
AB  - Previous physiological studies [e.g., Bieser and Muller-Preuss, Exp. Brain Res.
      108, 273-284 (1996); Schulze and Langner, J. Comp. Physiol. A 181, 651-663
      (1997); Steinschneider et al., J. Acoust. Soc. Am. 104, 2935-2955 (1998)] have
      suggested that neural activity in primary auditory cortex (A1) phase-locked to
      the waveform envelope of complex sounds with low (<300 Hz) periodicities may
      represent a neural correlate of roughness perception. However, a correspondence
      between these temporal response patterns and human psychophysical boundaries of
      roughness has not yet been demonstrated. The present study examined whether the
      degree of synchronized phase-locked activity of neuronal ensembles in A1 of the
      awake monkey evoked by complex tones parallels human psychoacoustic data defining
      the existence region and frequency dependence of roughness. Stimuli consisted of
      three consecutive harmonics of fundamental frequencies (f(0)s) ranging from 25 to
      4000 Hz. The center frequency of the complex tones was fixed at the best
      frequency (BF) of the cortical sites, which ranged from 0.3 to 10 kHz. Neural
      ensemble activity in the thalamorecipient zone (lower lamina III) and
      supragranular cortical laminae (upper lamina III and lamina II) was measured
      using multiunit activity and current source density techniques and the degree of
      phase-locking to the f0 was quantified by spectral analysis. In the
      thalamorecipient zone, the stimulus f0 at which phase-locking was maximal
      increased with BF and reached an upper limit between 75 and 150 Hz for BFs
      greater than about 3 kHz. Estimates of limiting phase-locking rates also
      increased with BF and approximated psychoacoustic values for the disappearance of
      roughness. These physiological relationships parallel human perceptual data and
      therefore support the relevance of phase-locked activity of neuronal ensembles in
      A1 for the physiological representation of roughness.

PMID- 10923890
TI  - Influence of peripheral resolvability on the perceptual segregation of harmonic
      complex tones differing in fundamental frequency.
AB  - Two experiments investigated the influence of resolvability on the perceptual
      organization of sequential harmonic complexes differing in fundamental frequency
      (F0). Using a constant-stimuli method, streaming scores for ABA-... sequences of
      harmonic complexes were measured as a function of the F0 difference between the A
      and B tones. In the first experiment, streaming scores were measured for harmonic
      complexes having two different nominal F0s (88 and 250 Hz) and filtered in three
      frequency regions (a LOW, a MID, and a HIGH region with corner frequencies of 125
      625 Hz, 1375-1875 Hz, and 3900-5400 Hz, respectively). Some streaming was
      observed in the HIGH region (in which the harmonics were always unresolved) but
      streaming scores remained generally lower than in the LOW and MID regions. The
      second experiment verified that the streaming observed in the HIGH region was not
      due to the use of distortion products. Overall, the results indicated that
      although streaming can occur in the absence of spectral cues, the degree of
      resolvability of the harmonics has a significant influence.

PMID- 10923889
TI  - Complex tone processing in primary auditory cortex of the awake monkey. II. Pitch
      versus critical band representation.
AB  - Noninvasive neurophysiological studies in humans support the existence of an
      orthogonal spatial representation of pure tone frequency and complex tone pitch
      in auditory cortex [Langner et al., J. Comp. Physiol. A 181, 665-676 (1997)].
      However, since this topographic organization is based on neuromagnetic responses
      evoked by wideband harmonic complexes (HCs) of variable fundamental frequency
      (f0), and thus interharmonic frequency separation (deltaF), critical band
      filtering effects due to differential resolvability of harmonics may have
      contributed to shaping these responses. To test this hypothesis, the present
      study examined responses evoked by three-component HCs of variable f0 in primary
      auditory cortex (A1) of the awake monkey. The center frequency of the HCs was
      fixed at the best frequency (BF) of the cortical site. Auditory evoked potential
      (AEP), multiunit activity, and current source density techniques were used to
      evaluate A1 responses as a function of f0 (=deltaF). Generally, amplitudes of
      nearly all response components increased with f0, such that maximal responses
      were evoked by HCs comprised of low-order resolved harmonics. Statistically
      significant increases in response amplitude typically occurred at deltaFs between
      10% and 20% of center frequency, suggestive of critical bandlike behavior.
      Complex tone response amplitudes also reflected nonlinear summation in that they
      could not be predicted by the pure tone frequency sensitivity curves of the
      cortical sites. A mechanism accounting for the observed results is proposed which
      involves mutual lateral inhibitory interactions between responses evoked by
      stimulus components lying within the same critical band. As intracortical AEP
      components likely to be propagated to the scalp were also strongly modulated by
      deltaF, these findings indicate that noninvasive recordings of responses to
      complex sounds may require a consideration of critical band effects in their
      interpretation.

PMID- 10923891
TI  - On the dichotic pitch of simultaneously presented interaurally delayed white
      noises. Implications for binaural theory.
AB  - A dichotic pitch known as Fourcin Pitch (FP) is perceived when two independent
      interaurally delayed white noises are presented simultaneously. Experiments in
      the past mainly dealt with stimulus situations where one interaural delay was
      smaller than 4 ms and the other was in the range 0-10 ms. Here, experiments are
      reported showing a novel pitch percept that occurs when one noise is interaurally
      delayed at the left ear and the other noise is about equally delayed at the right
      ear, for delays in the range of 4-10 ms. It is shown that, for both the
      previously reported FP and the novel pitch, the Central Spectrum (CS) theory
      [Raatgever and Bilsen, J. Acoust. Soc. Am. 80, 429-441 (1986)] provides a correct
      prediction of both the pitch value and the lateral position of the pitch image,
      where other current theories partly or completely fail. Further experiments
      indicate that the lateralized position of the pitch image is essentially not
      influenced by an interaural intensity difference (IID). This is also predicted by
      the CS model and leads to the generalized conclusion that interaural time and
      intensity differences are processed separately in the auditory system until, at
      least, the level where the dichotic pitch is generated.

PMID- 10923892
TI  - On the role of envelope fluctuation processing in spectral masking.
AB  - This study examines the role of temporal cues in spectral masking, such as beats
      and intrinsic envelope fluctuations. Predictions from the modulation-filterbank
      model developed by Dau et al. [J. Acoust. Soc. Am. 102, 2906-2919 (1997)] are
      compared to average masking patterns from Moore et al. [J. Acoust. Soc. Am. 104,
      1023-1038 (1998)]. In these experiments, tones and narrow-band noises have been
      used as the signal and the masker, so that all four signal-masker combinations
      are considered. In addition, model predictions are compared with new experimental
      data in conditions of notched-noise masking, where the masker consisted of two
      narrow-band noises whose bandwidth and frequency separation were varied
      systematically. The model uses a peripheral filtering stage with linear and
      symmetric Gammatone filters, an adaptation stage that includes a static
      compressive nonlinearity for stationary input stumuli and a higher sensitivity
      for envelope fluctuation, and a modulation filterbank that analyzes the output
      for each peripheral channel. For low and medium masker levels, the model accounts
      very well for the masking patterns in all signal-masker conditions, as well as
      for the notched-noise conditions. In contrast, predictions from a version of the
      model that acts like an energy detector account for only some of the notched
      noise data, and generally do not account for the shape of the masking patterns.
      For a high masker level, the simulations suggest the use of asymmetric filters,
      with a steeper high-frequency slope than is used in the linear model, consistent
      with results from previous studies. In addition, several nonlinear effects become
      apparent at this masker level, which cannot be accounted for by the current
      model.

PMID- 10923893
TI  - Detection of whale calls in noise: performance comparison between a beluga whale,
      human listeners, and a neural network.
AB  - This article examines the masking by anthropogenic noise of beluga whale calls.
      Results from human masking experiments and a software backpropagation neural
      network are compared to the performance of a trained beluga whale. The goal was
      to find an accurate, reliable, and fast model to replace lengthy and expensive
      animal experiments. A beluga call was masked by three types of noise, an
      icebreaker's bubbler system and propeller noise, and ambient arctic ice-cracking
      noise. Both the human experiment and the neural network successfully modeled the
      beluga data in the sense that they classified the noises in the same order from
      strongest to weakest masking as the whale and with similar call-detection
      thresholds. The neural network slightly outperformed the humans. Both models were
      then used to predict the masking of a fourth type of noise, Gaussian white noise.
      Their prediction ability was judged by returning to the aquarium to measure
      masked-hearing thresholds of a beluga in white noise. Both models and the whale
      identified bubbler noise as the strongest masker, followed by ramming, then white
      noise. Natural ice-cracking noise masked the least. However, the humans and the
      neural network slightly overpredicted the amount of masking for white noise. This
      is neglecting individual variation in belugas, because only one animal could be
      trained. Comparing the human model to the neural network model, the latter has
      the advantage of objectivity, reproducibility of results, and efficiency,
      particularly if the interference of a large number of signals and noise is to be
      examined.

PMID- 10923894
TI  - The effect of modulation rate on the detection of frequency modulation and
      mistuning of complex tones.
AB  - Experiment 1 measured frequency modulation detection thresholds (FMTs) for
      harmonic complex tones as a function of modulation rate. Six complexes were used,
      with fundamental frequencies (F0s) of either 88 or 250 Hz, bandpass filtered into
      a LOW (125-625 Hz), MID (1375-1875 Hz) or HIGH (3900-5400 Hz) frequency region.
      The FMTs were about an order of magnitude greater for the three complexes whose
      harmonics were unresolved by the peripheral auditory system (F0 = 88 Hz in the
      MID region and both F0s in the HIGH region) than for the other three complexes,
      which contained some resolved harmonics. Thresholds increased with increases in
      FM rate above 2 Hz for all conditions. The increase was larger when the F0 was 88
      Hz than when it was 250 Hz, and was also larger in the LOW than in the MID and
      HIGH regions. Experiment 2 measured thresholds for detecting mistuning produced
      by modulating the F0s of two simultaneously presented complexes out of phase by
      180 degrees. The size of the resulting mistuning oscillates at a rate equal to
      the rate of FM applied to the two carriers. At low FM rates, thresholds were
      lowest when the harmonics were either resolved for both complexes or unresolved
      for both complexes, and highest when resolvability differed across complexes. For
      pairs of complexes with resolved harmonics, mistuning thresholds increased
      dramatically as the FM rate was increased above 2-5 Hz, in a way which could not
      be accounted for by the effect of modulation rate on the FMTs for the individual
      complexes. A third experiment, in which listeners detected constant ("static")
      mistuning between pairs of frequency-modulated complexes, provided evidence that
      this deterioration was due the harmonics in one of the two "resolved" complexes
      becoming unresolved at high FM rates, when analyzed over some finite time window.
      It is concluded that the detection of time-varying mistuning between groups of
      harmonics is limited by factors that are not apparent in FM detection data.

PMID- 10923895
TI  - The lateralization of simple dichotic pitches.
AB  - A "simple" dichotic pitch arises when a single narrow band possesses a different
      interaural configuration from a surrounding broadband noise whose interaural
      configuration is uniform and correlated. Such pitches were created by
      interaurally decorrelating a narrow band (experiment 1) or by giving a narrow
      band a different interaural time difference from the noise (experiment 2). Using
      an adaptive forced-choice procedure, listeners adjusted the interaural intensity
      difference of "pointers" to match their lateralization to that of the dichotic
      pitches. The primary determinants of lateralization were the interaural
      configuration of the broadband noise (experiment 1), the center frequency of the
      narrow band (experiment 1), and its interaural configuration (experiment 2). The
      ability of two computational models to predict these results was evaluated. A
      version of the central-spectrum model [J. Raatgever and F. A. Bilsen, J. Acoust.
      Soc. Am. 80, 429-441 (1986)] incorporating realistic frequency selectivity
      accounted for the main results of experiment 1 but not experiment 2. A new
      "reconstruction-comparison" model accounted for the main results of both
      experiments. To accommodate the variables shown to influence lateralization, this
      model segregates evidence of the dichotic pitch from the noise, reconstructs the
      cross-correlogram of the noise, and compares it with the cross-correlogram of the
      original stimulus.

PMID- 10923896
TI  - Effects of reverberation on spatial, prosodic, and vocal-tract size cues to
      selective attention.
AB  - Three experiments explored the resistance to simulated reverberation of various
      cues for selective attention. Listeners decided which of two simultaneous target
      words belonged to an attended rather than to a simultaneous unattended sentence.
      Attended and unattended sentences were spatially separated using interaural time
      differences (ITDs) of 0, +/-45, +/-91 or +/-181 micros. Experiment 1 used
      sentences resynthesized on a monotone, with sentence pairs having F0 differences
      of 0, 1, 2, or 4 semitones. Listeners' weak preference for the target word with
      the same monotonous F0 as the attended sentence was eliminated by reverberation.
      Experiment 1 also showed that listeners' ability to use ITD differences was
      seriously impaired by reverberation although some ability remained for the
      longest ITD tested. In experiment 2 the sentences were spoken with natural
      prosody, with sentence stress in different places in the attended and unattended
      sentences. The overall F0 of each sentence was shifted by a constant amount on a
      log scale to bring the F0 trajectories of the target words either closer together
      or further apart. These prosodic manipulations were generally more resistant to
      reverberation than were the ITD differences. In experiment 3, adding a large
      difference in vocal-tract size (+/- 15%) to the prosodic cues produced a high
      level of performance which was very resistant to reverberation. The experiments
      show that the natural prosody and vocal-tract size differences between talkers
      that were used retain their efficacy in helping selective attention under
      conditions of reverberation better than do interaural time differences.

PMID- 10923897
TI  - Acoustic modeling of American English /r/.
AB  - Recent advances in physiological data collection methods have made it possible to
      test the accuracy of predictions against speaker-specific vocal tracts and
      acoustic patterns. Vocal tract dimensions for /r/ derived via magnetic-resonance
      imaging (MRI) for two speakers of American English [Alwan, Narayanan, and Haker,
      J. Acoust. Soc. Am. 101, 1078-1089 (1997)] were used to construct models of the
      acoustics of /r/. Because previous models have not sufficiently accounted for the
      very low F3 characteristic of /r/, the aim was to match formant frequencies
      predicted by the models to the full range of formant frequency values produced by
      the speakers in recordings of real words containing /r/. In one set of
      experiments, area functions derived from MRI data were used to argue that the
      Perturbation Theory of tube acoustics cannot adequately account for /r/,
      primarily because predicted locations did not match speakers' actual constriction
      locations. Different models of the acoustics of /r/ were tested using the Maeda
      computer simulation program [Maeda, Speech Commun. 1, 199-299 (1982)]; the
      supralingual vocal-tract dimensions reported in Alwan et al. were found to be
      adequate at predicting only the highest of attested F3 values. By using (1) a
      recently developed adaptation of the Maeda model that incorporates the sublingual
      space as a side branch from the front cavity, and by including (2) the sublingual
      space as an increment to the dimensions of the front cavity, the mid-to-low
      values of the speakers' F3 range were matched. Finally, a simple tube model with
      dimensions derived from MRI data was developed to account for cavity
      affiliations. This confirmed F3 as a front cavity resonance, and variations in
      F1, F2, and F4 as arising from mid- and back-cavity geometries. Possible trading
      relations for F3 lowering based on different acoustic mechanisms for extending
      the front cavity are also proposed.

PMID- 10923898
TI  - Reconstruction of bowing point friction force in a bowed string
AB  - A method is presented for reconstructing the friction force and the velocity at
      the bowing point of a string excited by a rosined bow sliding transverse to the
      string. Two versions of the method of reconstruction are presented, each
      approximate in different ways, but both capable of sufficient accuracy to allow
      useful application to problems of understanding frictional interactions in this
      dynamical system. The method is illustrated with simulated data to verify its
      accuracy, and results are shown for two contrasting cases of observed stick-slip
      string motion. As has been found in other investigations, the friction force
      during sliding is not determined by the instantaneous sliding speed. The results
      seem to be compatible with a thermally based model of rosin friction.

PMID- 10923899
TI  - Evolution of the vibrational behavior of a guitar soundboard along successive
      construction phases by means of the modal analysis technique
AB  - The crucial piece of a craft guitar is the soundboard since it determines the
      quality of the sound given by the instrument. From the initial phase (the gross
      plate with no hole) until the last construction phase (the plate with the full
      structure) several stages are followed to modify the dynamic behavior of the
      structure and hence the acoustic response of the final guitar. The aim of this
      work is to analyze the effect of each modification on the vibrational response of
      the plate. With this in mind, an experimental modal analysis of all the
      construction phases has been performed in the low frequency range under free
      conditions. The response of the plate in each stage is defined by vibration
      patterns, resonance frequencies, quality factors, and admittance curves.

PMID- 10923900
TI  - Measurements and efficient simulations of bowed bars
AB  - Bowing bar percussion instruments is an increasing part of the repertoire of
      modern composition and performance. Yet the system has not been studied
      systematically. In this paper experimental measurements of bars of bar percussion
      instruments bowed by a double bass bow and by a bowing machine are presented.
      They examine the relationships between performance parameters and perceptional
      parameters which are relevant for musical performance. In addition, a new
      efficient simulation method using a time-domain approach has been developed and
      the measured results are compared to the simulation. Most measurement results are
      in good qualitative agreement with the known results of the bowed string. The
      spectrum of the bowed bar is observed to be harmonic, independent of the
      harmonicity or inharmonicity of the eigenfrequencies of the bar. Important
      distinctions from the known results of the bowed string are the weakness or
      independence of bowing force and velocity on the fundamental frequency and the
      spectral content of the produced sound. Simulations show qualitative agreement
      with the measurements.

PMID- 10923901
TI  - Constancy of loudness of pipe organ sounds at different locations in an
      auditorium
AB  - Pipe organ sounds, as judged by ear, tend to remain constant across different
      locations in an auditorium, yet the SPL of line spectra may vary by a maximum of
      26 dB (mean 8.98 dB, s.d. 2.5), and the overall level may vary, typically, 10 to
      12 dB from location to location. However, organs are designed, listened to, and
      regulated using the psychophysical units of loudness and timbre, and it is
      possible that the heard sound constancy exists at the psychophysical level. The
      present work recorded the sound of the C's and G's of pipe organ stops at three
      different locations in a church. The sound pressure levels were transformed to
      loudness. Similarity of loudness across the locations was measured two ways.
      First, the bass to treble distribution of loudness across the compass was
      measured using cross-correlation functions across pairs of locations. Second, the
      degree of similarity of loudness at the different locations was quantified by
      calculating ratios of loudness between the different locations. By these
      measures, the bass to treble loudness distribution and absolute loudness of the
      reeds were found to be nearly identical at the three locations. Two
      psychophysical processes were shown to be responsible for the loudness constancy.
      The first depended upon the power summation of harmonics within each third octave
      band above band 9 which contain two or more harmonics. The power summation of
      these harmonics greatly reduced the effect of SPL variability of the line spectra
      contained within these higher numbered bands. The second depended upon
      interharmonic loudness summation and upward masking of the first six harmonics.
      Greater loudness variability at the different locations was found after
      transforming the SPL measurements of two 8-ft diapasons to loudness compared with
      the reeds. The larger loudness variability was due to the smaller number of
      harmonics above the third of the diapasons compared with the reeds. The
      psychoacoustic measures indicate what a listener will hear as he/she moves among
      the locations.

PMID- 10923902
TI  - Oscillating reed valves--an experimental study
AB  - The results of experiments on the threshold behavior and large-amplitude
      oscillation of "outward-swinging door" vibrating flap valves in an air
      environment are reported and compared with the predictions of a simple nonlinear
      theory that parametrizes aerodynamic effects by means of a simple damping
      coefficient together with a contraction coefficient for the flow. The agreement
      is acceptably good for the threshold blowing pressure for valve oscillation, the
      large-signal vibration amplitude, the pressure jump in the transition from
      threshold to large-signal behavior, and the variation in vibration frequency, all
      as functions of reservoir volume. The calculated pressure waveform in the
      reservoir has the observed phase and magnitude but fails to reproduce finer
      details. It is concluded that the simple theory provides an adequate account of
      the behavior of such valves. There are just two parameters in the theory,
      describing jet contraction and aerodynamic damping, respectively. Since these may
      depend significantly upon the detailed geometry, valves with different shapes may
      behave in quantitatively different ways.

PMID- 10923903
TI  - Synthesis and modification of the whistles of the bottlenose dolphin, Tursiops
      truncatus.
AB  - A signal-processing algorithm was developed to analyze harmonic frequency
      modulated sounds, to modify the parameters of the analyzed signal, and to
      synthesize a new analytically specified signal that resembles the original signal
      in specified features. This algorithm was used with dolphin whistles, a frequency
      modulated harmonic signal that has typically been described in terms of its
      contour, or pattern of modulation of the fundamental frequency. In order to test
      whether other features may also be salient to dolphins, the whistle analysis
      calculates the energies at the harmonics as well as the fundamental frequency of
      the whistle. The modification part of the algorithm can set all of these energies
      to a constant, can shift the whistle frequency, and can expand or compress the
      time base or the frequency of the whistle. The synthesis part of the algorithm
      then synthesizes a waveform based upon the energies and frequencies of the
      fundamental and first two harmonics. These synthetic whistles will be useful for
      evaluating what acoustic features dolphins use in discriminating different
      whistles.

PMID- 10923905
TI  - Modeling of high-intensity focused ultrasound-induced lesions in the presence of
      cavitation bubbles
AB  - The classical "Bio Heat Transfer Equation (BHTE)" model is adapted to take into
      account the effects of oscillating microbubbles that occur naturally in the
      tissue during high-intensity focused ultrasound (HIFU) treatment. First, the
      Gilmore-Akulichev model is used to quantify the acoustic pressure scattered by
      microbubbles submitted to HIFU. Because this scattered pressure is not
      monochromatic, the concept of harmonic attenuation is introduced and a global
      attenuation coefficient is estimated for bubble-filled tissues. The first results
      show that this global attenuation coefficient varies significantly with respect
      to several parameters such as the frequency and the density of microbubbles in
      the medium, but also with respect to the incident acoustic pressure which thus
      becomes a transcendental function. Under these conditions, a layer-by-layer
      modeling, in the direction of propagation, is proposed to calculate the
      ultrasonic beam. Finally, the BHTE is solved and the HIFU-induced lesions are
      estimated by the calculation of the thermal dose. Using this model, it can be
      observed first that, when the firing power increases, the lesion develops clearly
      in the direction of the transducer, with a shape agreeing with in vivo
      experimentation. Next, it is observed that the lesion can be significantly
      modified in size and position, if an interface (skin or inner wall) is simulated
      as a zone with multiple cavitation nuclei. With a firing power increase, it is
      also shown how a secondary lesion can appear at the interface and how, beyond a
      certain threshold, this lesion develops at the main lesion expense. Finally, a
      better in-depth homogeneity of lesions is observed when the acoustic frequency of
      HIFU is increased.

PMID- 10923904
TI  - Auditory and behavioral responses of bottlenose dolphins (Tursiops truncatus) and
      a beluga whale (Delphinapterus leucas) to impulsive sounds resembling distant
      signatures of underwater explosions.
AB  - A behavioral response paradigm was used to measure masked underwater hearing
      thresholds in two bottlenose dolphins and one beluga whale before and after
      exposure to impulsive underwater sounds with waveforms resembling distant
      signatures of underwater explosions. An array of piezoelectric transducers was
      used to generate impulsive sounds with waveforms approximating those predicted
      from 5 or 500 kg HBX-1 charges at ranges from 1.5 to 55.6 km. At the conclusion
      of the study, no temporary shifts in masked-hearing thresholds (MTTSs), defined
      as a 6-dB or larger increase in threshold over pre-exposure levels, had been
      observed at the highest impulse level generated (500 kg at 1.7 km, peak pressure
      70 kPa); however, disruptions of the animals' trained behaviors began to occur at
      exposures corresponding to 5 kg at 9.3 km and 5 kg at 1.5 km for the dolphins and
      500 kg at 1.9 km for the beluga whale. These data are the first direct
      information regarding the effects of distant underwater explosion signatures on
      the hearing abilities of odontocetes.

PMID- 10923906
TI  - Field characterization of therapeutic ultrasound phased arrays through forward
      and backward planar projection
AB  - Spatial planar projection techniques propagate field measurements from a single
      plane in front of a transmitter to arbitrary new planes closer to or further away
      from the source. A linear wave vector frequency-domain projection algorithm is
      applied to the acoustic fields measured from several focused transducer arrays
      designed for ultrasound therapy. A polyvinylidene difluoride hydrophone is first
      scanned in a water tank over a plane using a three-dimensional positioning system
      to measure the complex pressure field as a function of position. The field is
      then projected to a series of new planes using the algorithm. Results of the
      projected fields are compared with direct measurements taken at corresponding
      distances. Excellent correlation is found between the projected and measured
      data. The method is shown to be accurate for use with phase-controlled field
      patterns, providing a rapid and accurate method for obtaining field information
      over a large spatial volume. This method can significantly simplify the
      characterization procedure required for phased-array application used for
      therapy. Most significantly, the wavefront propagated back to a phased array can
      be used to predict the field produced by different phase and amplitude settings
      of the array elements. A field back-projected to the source could be used as an
      improved source function in acoustic modeling.

PMID- 10923907
TI  - Near-field-far-field measurement of loudspeaker response

PMID- 10923908
TI  - A comparative study of transforms for use in digital audio data compression.
AB  - This paper provides a subjective quality analysis of transforms used in audio
      compression algorithms for a class of music signals. A 34-subject listener test
      compares three transforms in conjunction with an MPEG I layer 1 compression
      scheme. One test compares the performances of the discrete wavelet packet
      transform (DWPT) and the modified discrete cosine transform (MDCT) used in MPEG.
      Another test compares the performances of a DWPT eight-level nonuniform critical
      band split and a DWPT five-level uniform subband split. Results indicate that the
      critical-band split provides significantly better quality than the uniform
      subband split for sounds with tonal and strong low-frequency content, while the
      DWPT outperforms the MDCT with significant improvement for nontonal sounds.

PMID- 10923909
TI  - The role of magnesium in the susceptibility of soldiers to noise-induced hearing
      loss.
AB  - A number of studies have demonstrated that magnesium, administered
      prophylactically, can reduce the amount of hearing loss resulting from noise
      exposure. This study explored the possible role of naturally occurring body
      magnesium concentration in susceptibility of soldiers to noise-induced hearing
      loss. Participants were 68 adult males who had received extensive noise exposure
      over several years as a result of training with weapon systems. Each participant
      provided a pure-tone audiogram, blood sample, and noise-exposure history. A
      variety of pure-tone indices was correlated with serum magnesium levels as
      determined by atomic absorption spectroscopy. No significant correlations were
      observed between any audiometric index and body magnesium. The results of this
      study, therefore, do not support the hypothesis that there is a strong
      association between naturally occurring body magnesium and susceptibility to
      noise-induced hearing loss.

PMID- 10923910
TI  - Line spectral frequencies are poles and zeros of the glottal driving-point
      impedance of a discrete matched-impedance vocal tract model.
AB  - This correspondence demonstrates that the line spectral frequencies (LSFs) are
      the pole and zero frequencies of the glottal driving-point impedance of a
      discrete matched-impedance vocal-tract model. Several well-known characteristics
      of the LSFs, including the interlacing of pole and zero frequencies, are shown to
      follow naturally from this proof.

PMID- 10923911
TI  - Digital pathology--the big picture.

PMID- 10923912
TI  - A prospective trial of telepathology for intraoperative consultation (frozen
      sections).
AB  - Telepathology is a maturing technology that, for a variety of reasons, has not
      been widely deployed. In addition, clinical validation is relatively modest
      compared with accepted telemedicine applications such as teleradiology. A
      prototype telepathology system (Tele-Path(sm)) featuring high-resolution images
      selected from a remote microscope site has been developed at the University of
      Alabama at Birmingham (UAB). To validate the diagnostic efficacy of the system, a
      prospective study was undertaken of parallel diagnoses by conventional microscopy
      and telepathology with a remotely operated microscope. Slides from 99
      intraoperative consultations from 29 tissue/ organ sites in the University of
      Alabama Hospitals by 9 academic pathologists were used in the study. Each
      microscopic and telepathology diagnosis was compared with the final diagnosis
      rendered by a referee pathologist. Diagnoses were classified as correct, false
      positive, or false negative or classification error. Of the 99 frozen sections
      evaluated, 3 cases were deferred. Of the remaining 96 cases, 2 received incorrect
      diagnoses in both the microscopic and telepathology arms of the study. Three
      errors occurred only in the telepathology arm. There was 1 false-positive
      diagnosis, 1 false-negative diagnosis, and 1 classification error. Statistical
      analysis indicated no significant difference between telepathology and
      conventional microscopy. Qualitative data indicated that the pathologists were
      generally satisfied with the performance of the system. Telepathology using this
      system paradigm is sufficiently accurate for real time utilization in a complex
      surgical environment. Telepathology therefore may be an effective model to
      support the surgical services of hospitals lacking full-time pathology coverage,
      resulting in full-time access to anatomic pathology services.

PMID- 10923913
TI  - Outpatient frozen sections by telepathology in a Veterans Administration medical
      center.
AB  - A relatively simple telepathology system is described for evaluating the margins
      of excision of cutaneous basal and squamous carcinomas. The system uses a
      microscope with a built-in television camera, but no eyepieces. The image is
      projected onto an adjacent monitor and transmitted by T1 line at 768 Kbs to a
      remote, large screen monitor. The microscope is operated by the surgeon under the
      telephone direction of the pathologist at the remote site. In a series of 66
      cases involving more than 400 individual tissue blocks, we have had only 2 cases
      with false-negative interpretations and 2 in which the block was not fully
      displayed on the frozen section. In 15 cases, 1 or more surgical margins were
      positive, and the surgeon proceeded to excise additional tissue. Our success is
      attributed to dedicated involvement by the surgeon, very high-quality frozen
      sections, and the experience of the pathologist.

PMID- 10923914
TI  - Growth hormone-releasing hormone expression in pituitary somatotroph adenomas,
      studied by immunohistochemistry and in situ hybridization using catalyzed signal
      amplification system.
AB  - Growth hormone-releasing hormone (GHRH) is a well-known hypothalamic hormone that
      stimulates the synthesis and release of growth hormone (GH) as well as the
      proliferation of GH-producing cells in the anterior pituitary gland. Recent
      reports have shown GHRH synthesis in pituitary somatotroph adenomas, but GHRH
      immunoreactivity has not been shown in previous studies. To confirm the role of
      locally generated GHRH for the progression of somatotroph adenomas, we
      investigated the expression of GHRH in 25 pituitary somatotroph adenomas
      immunohistochemically, through the use of both conventional avidin-biotin-complex
      (ABC) method and novel catalyzed signal amplified (CSA) system. In addition, we
      investigated the expression of GHRH mRNA and GHRH receptor mRNA with in situ
      hybridization (ISH) using the CSA system. The weak immunopositivity of GHRH was
      observed in only 2 adenomas (8.0%) of 25 somatotroph adenomas using the ABC
      method. In contrast, 15 adenomas (60.0%) of 25 somatotroph adenomas were
      immunopositive for GHRH, as shown by CSA system. Very few of nonsomatotroph
      adenomas were immunopositive for GHRH using the CSA system. The expression of
      GHRH mRNA was confirmed, using the CSA-ISH system in 13 adenomas (72.2%) of 18
      somatotroph adenomas. In 11 adenomas (61.1%) of 18 somatotrophic adenomas, the
      expression of GHRH receptor mRNA was demonstrated using the CSA-ISH system. This
      is a first report that clarified histopathologically GHRH production in pituitary
      somatotrophic adenomas. The demonstration of GHRH and its receptor expression is
      meaningful in clarifying the autocrine or paracrine regulation of GHRH in GH
      production and progression of pituitary somatotroph adenomas.

PMID- 10923915
TI  - K-ras gene mutations and loss of heterozygosity at the p53 gene locus relative to
      histological characteristics of mucin-producing tumors of the pancreas.
AB  - Mucin-producing tumors (MPTs) of the pancreas accompanied by carcinomas usually
      include various grades of dysplasia in the ductal epithelium, and invasive areas
      are histologically similar to those of common invasive ductal carcinomas,
      suggesting that MPTs provide a good tool to investigate early stages of
      pancreatic carcinogenesis. Thus, to clarify genetic alterations in the early
      stage of pancreatic carcinogenesis, we analyzed K-ras gene mutations and loss of
      heterozygosity (LOH) at the p53 gene locus using 37 cases of MPTs harboring
      dysplastic epithelium. Further, we conducted an extended, multifocal
      microdissection analysis focusing on the histological features of ductal
      epithelium and the distribution of genetic alterations for 3 cases of MPT
      positive for LOH of the p53 gene to determine the relation to tumor progression.
      K-ras gene mutations were detected with high frequency in 50% or more cases of
      the adenomas (14 of 19), borderline tumors (4 of 7), and carcinomas (8 of 11),
      whereas LOH of the p53 gene was limited to carcinomas (3 of 5 informative cases,
      60%) and always accompanied by K-ras gene mutation. Investigation of a total of
      126 microdissection sites from 3 cases showed the presence of K-ras gene
      mutations in mild dysplasia and all (100%) regions of moderate or more marked
      dysplasia, whereas LOH of the p53 gene showed more gradual tendency to increase
      with grade from moderate dysplasia. In addition, the multifocal genetic analysis
      showed K-ras gene mutations to be widely distributed throughout tumors, whereas
      LOH of the p53 gene was localized to 1 or a few areas. Further, topographically
      delimited areas with the same histology in the same tumor did not always show the
      same genetic alteration. In conclusion, we could confirm that both the K-ras and
      p53 gene alterations occur in the intraductal stage of MPT, and the latter is
      superimposed on the former during the course of tumor progression. However, the
      pattern of association of histological features with genetic alteration differs
      from tumor to tumor.

PMID- 10923916
TI  - Gene expression of vascular endothelial growth factor in giant cell tumors of
      bone.
AB  - The production of vascular endothelial growth factors (VEGF), a major cause of
      neoangiogenesis, is a prerequisite for tumor growth and invasion. VEGF have also
      been shown to be important for the formation of osteoclasts. Because giant cell
      tumors of bone (GCT) are frequently hypervascular and have the ability to recruit
      macrophages and multinucleated osteoclast-like giant cells, we evaluated the
      levels of VEGF gene transcript in several of these tumors using Northern blot
      analyses, semiquantitative reverse transcription polymerase chain reaction (RT
      PCR), fluorescence in situ hybridization (FISH), and immunohistochemistry. Our
      results showed that three major isoforms of VEGF (121, 165, and 189) were
      expressed in all cases of GCT investigated, with isoform 121 transcripts the most
      abundant. By both FISH and immunohistochemistry, we have shown that VEGF was
      present in spindle-shaped stromal-like tumor cells, round macrophage-like cells,
      and osteoclast-like multinucleate giant cells. Moreover, we have shown that the
      levels of VEGF gene expression but not microvessel density correlated with
      Enneking's clinical stage of GCT. There were higher levels of VEGF gene
      expression in stage III GCT than in stage I/II GCT (P < .0357). In conclusion,
      our results indicate that overexpression of VEGF may be associated with the
      advanced stage of the neoplasm.

PMID- 10923917
TI  - Skeletal muscle in routine tonsillectomy specimens: a common finding.
AB  - Over the past 10 years, 1 of the authors (D.G.) has been consulted about several
      medical legal cases involving complications allegedly related to excessive
      surgery as documented by finding skeletal muscle in tonsillectomy specimens. A
      review of the literature showed little information about the incidence of
      skeletal muscle in routine tonsillectomy specimens; therefore, this study was
      undertaken. Thirty sequential tonsillectomy specimens from patients with
      histories of hyperplastic tonsils (10 males, 20 females; ages 5, 17 to 39; mean
      age, 24.3 years) were processed routinely (1 section/tonsil), and evaluated on a
      retrospective basis using routine light microscopy (group 1). In addition, 20
      sequential tonsillectomy specimens were processed in a prospective fashion,
      excluding sleep apnea specimens (5 males, 15 females; ages 12 to 59 years; mean
      age, 28.9 years) (group 2). All specimens in the first group had lymphoid
      hyperplasia; 25 of the 30 (83%) had skeletal muscle in soft tissue adjacent to
      the lymphoid elements, 20 (67%) had seromucinous glands, and in 1 there was a
      focus of cartilage. In group 2, 18 had lymphoid hyperplasia and 2 contained
      carcinomas; 19 of 20 contained skeletal muscle ranging from a single fiber to
      abundant, multifocal areas with muscle, 16 (80%) had seromucinous glands, and 4
      contained areas with cartilage. Additional tissue from the specimen without
      muscle and the tonsil with a single fiber was processed, and abundant skeletal
      muscle was identified in each. One may conclude that skeletal muscle is very
      frequently found in routine tonsillectomy specimens and, by itself, is not an
      indication of inappropriate surgical technique.

PMID- 10923918
TI  - Protein expression of double-stranded RNA-activated protein kinase in thyroid
      carcinomas: correlations with histologic types, pathologic parameters, and Ki-67
      labeling.
AB  - There have been no reports evaluating double-stranded RNA-activated protein
      kinase (PKR) in thyroid carcinomas. Therefore, we investigated the protein
      expression of PKR and its correlations with several pathologic parameters and Ki
      67 labeling in 86 thyroid carcinomas, using a semiquantitative scoring method.
      Western blot analysis showed a specific band of 68 kDa corresponding to PKR
      molecular weight in 9 selected fresh samples. In immunohistochemistry of archival
      samples, PKR was expressed in 77 of 86 (90%) cases. The positive rate and PKR
      score were significantly higher in papillary carcinoma (75 of 80, 94%, PKR score
      = 4.47 +/- 2.17) than in nonpapillary carcinomas (2 of 6, 33%, PKR score = 1.50
      +/- 2.81). Nontumorous thyroid showed no or faint "baseline" PKR expression.
      There were no significant differences between the PKR score and tumor size, tumor
      invasion, capsular invasion, or lymph node metastasis. However, there were
      significant differences between the PKR score and vascular invasion or presence
      of satellite tumor nodules, the PKR score being higher in cases with more
      vascular invasion and in cases with satellite tumor nodules than in cases without
      them. Ki-67 labeling showed a reverse correlation with the PKR score, being the
      highest in cases with low PKR scores. These results suggest that follicular cells
      newly express PKR during thyroid carcinogenesis, that PKR is more expressed in
      papillary carcinoma than in nonpapillary carcinoma, that PKR expression may be
      associated with high vascular invasion and satellite nodules, and that PKR
      expression is linked to low cell proliferative activity.

PMID- 10923919
TI  - Hepatic stellate cell activation in nonalcoholic steatohepatitis and fatty liver.
AB  - Factors associated with the development of fibrosis in nonalcoholic
      steatohepatitis (NASH) are largely unknown, although an association with
      increased hepatic iron has been suggested. Hepatic stellate cells are the
      principal collagen-producing cells in many liver diseases and when activated
      express alpha-smooth muscle actin (alpha-SMA). Hepatic stellate cell activation
      and association with fibrosis, necroinflammatory activity, steatosis, and
      stainable iron in 60 cases of NASH and 16 cases of steatosis were evaluated. All
      76 patients were obese or had other risk factors for NASH. All biopsy specimens
      were stained for alpha-smooth muscle actin to evaluate the pattern of hepatic
      stellate cell activation and were evaluated for inflammatory activity (0 to 3),
      fibrosis (0 to 4), and stainable iron stores (0 to 4). The zonal location of
      activated stellate cells was recorded, and the degree of activation was graded as
      high-grade or low-grade based on the percentage of lobular alpha-SMA+ cells.
      Activated stellate cells were identified in the hepatic lobule in 74 of 76 biopsy
      specimens and graded as low-grade in 26 and high-grade in 48. Zone 3 was involved
      in 72 of 74 positive cases, and in 33 cases, the activated stellate cells were
      preferentially located in zone 3. The degree of stellate cell activation
      correlated with fibrosis but not with inflammatory activity, severity of
      steatosis, or stainable iron. In most cases, the degree of stellate cell
      activation paralleled the degree of hepatic fibrosis, but in 25 cases, the degree
      of hepatic stellate cell activation was greater than expected, raising the
      question of whether such patients are at risk for disease progression.

PMID- 10923920
TI  - Hybrid system for telepathology.
AB  - We introduce a novel hybrid telepathology system providing simultaneous
      transmission of both real-time microscopy and static imagery at a reasonable
      cost. It is capable of capturing static, true color images at resolution of 1,520
      x 1,144 pixels and providing live transmission of real-time video images of the
      glass slide in Common Intermediate Format (CIF), which can be viewed at 1,024 x
      768 pixels or higher. Instant freeze function can be enabled with 4x CIF
      resolution (1,408 x 1,152 pixels). This system comprises the advantages of real
      time transmission and high-resolution static imagery, while direct visual and
      audio communications are maintained at the same time. It uses standard 'off-the
      shelf' components with a total cost of around $30,000 to $40,000. We also
      conclude that differences in telepathology modality and image quality have an
      impact on diagnostic accuracy and should be considered for discussion and
      standards development by professional organizations in the field of
      telepathology. An effort to ascertain the diagnostic limitations of various
      telepathology modalities is essential to the future use of this modality of
      pathology practice.

PMID- 10923921
TI  - Expression of cathepsin K in chordoma.
AB  - Invasive growth of chordoma is accompanied by severe destruction of adjacent bone
      tissue, a fact that requires high proteolytic activity at the tumor invasion
      fronts. In this context, cathepsin K is a candidate molecule. It is a protease
      with high collagenolytic and elastinolytic activity and previously thought to be
      restricted to osteoclasts and osteoclast-mediated bone resorption. In this study,
      44 cases of chordoma of sphenooccipital localization, and 10 embryo-fetal
      specimens including chorda dorsalis were studied immunohistochemically for their
      expression of cathepsin K. In 4 additional snap-frozen chordoma cases, the enzyme
      expression was investigated by reverse transcription polymerase chain reaction
      and enzyme histochemistry. Ten chondrosarcomas of the skull base served as
      controls. Various concentrations of cathepsin K mRNA could be seen in all snap
      frozen chordoma specimens. The protease was immunohistochemically expressed by
      the tumor cells. The immunoreactions were accentuated at the tumor invasion
      fronts. Enzyme histochemistry indicated a strong tumor cell-associated cathepsin
      K activity in invasive tumor components. In contrast to chordoma, cathepsin K was
      not significantly expressed in chorda dorsalis and chondrosarcoma of the skull
      base. In chondrosarcoma, protease expression was limited to osteoclastic cells
      localized between infiltrative tumor components and regular bone trabeculae. This
      study shows the significant expression and activity of cathepsin K in chordoma
      and implicates an important and direct role of this protease in the infiltrative
      growth of this tumor. This protease expression occurred during neoplastic
      transformation and did not appear in chorda dorsalis.

PMID- 10923922
TI  - Intrauterine inflammation at term: a histopathologic study.
AB  - This study was undertaken to examine the presence of inflammation of the uterine
      and gestational tissues as defined by histopathology in clinically noninfected
      women with term gestation and intact fetal membranes and to evaluate its
      correlation with measured clinical variables and neonatal and maternal clinical
      outcome. Two hundred sixteen clinically noninfected term parturients who
      underwent cesarean section with intact membranes were analyzed for the presence
      of inflammatory lesions of the gestational tissues and uterus. Nine hundred
      eighty-one histologic samples were studied, including 212 samples from both
      chorion membranes and umbilical cords, and 209 placental, 192 myometrial, and 156
      decidual samples. In 208 (96%) cases, either amniotic fluid (AF) or endometrial
      swab samples were cultivated for bacteria. In 148 (69%) cases, the AF leukocyte
      count was analyzed by the Gram stain method, and in 77 (36%), AF leukocyte
      esterase activity (LEA) was evaluated. Leukocytic infiltrations were present in
      samples from 41 (19%) women, varying from 2% to 10% in the different anatomic
      sites examined. However, after onset of labor, low-grade decidual inflammation
      was observed in 29% of cases. Cervical dilation (odds ratio, 4.7; 95% confidence
      interval, 2.4 to 9.3; P < .00003) and meconium-stained AF at the operation (odds
      ratio, 5.3; 95% confidence interval, 2.2 to 12.5; P < .00015) were associated
      with the histologic inflammatory lesions observed in decidual samples,
      independently of AF or endometrial microbial detection, AF leukocytes, or LEA.

PMID- 10923923
TI  - PCR analysis of IgH-gene rearrangements in small lymphoid infiltrates
      microdissected from sections of paraffin-embedded bone marrow biopsy specimens.
AB  - The differentiation of benign lymphoid infiltrates from nodular infiltrates of B
      cell lymphoma is difficult in bone marrow (BM) biopsy specimens taken from
      patients with non-Hodgkin's lymphoma (NHL). We investigated whether the
      determination of clonality by polymerase chain reaction (PCR) analysis of the
      immunoglobulin heavy chain (IgH) genes could be of help for the distinction of
      benign and malignant lymphoid infiltrates. BM biopsy specimens of 28 patients
      were studied, comparing PCR of entire bone marrow sections with microdissected
      nodular lymphoid infiltrates. Patients were divided into 4 groups according to
      morphologic criteria: group 1 (n = 12), positive for B-NHL infiltration; group 2
      (n = 5), suspicious for infiltration by known B-NHL; group 3 (n = 5),
      morphologically benign infiltrates in patients with B-NHL; group 4 (n = 6),
      benign lymphoid infiltrates in patients without history of B-NHL. PCR products
      were analyzed using polyacrylamide gels and a fragment length analysis system
      (Genescan). PCR of whole sections showed clonal amplification products in all
      cases of group 1 and 1 case of group 2. PCR analysis from microdissected nodular
      infiltrates showed the presence of a clonal B-cell population in 5 additional
      cases of groups 2 and 4. In 3 of these cases, clonal rearrangements of
      corresponding size were obtained from the primary lymphoma biopsy specimens. None
      of the cases of group 3 showed evidence of a clonal population with either
      technique. The results indicate that microdissection of small nodular lymphoid
      infiltrates from paraffin-BM sections increases the sensitivity of IgH gene
      rearrangement analysis. To avoid detection of biologically irrelevant clonal
      populations, comparison of PCR products obtained from the BM and the primary
      lymphoma biopsy is advisable.

PMID- 10923924
TI  - Interphase cytogenetics in oncocytic adenomas and carcinomas of the thyroid
      gland.
AB  - Follicular neoplasms of oncocytic type in the thyroid gland frequently cause
      diagnostic problems and prognostic uncertainties. To identify numerical
      chromosomal aberrations of possible pathogenetic importance, we determined
      chromosome copy numbers in situ in interphase nuclei of 31 oncocytic adenomas and
      25 oncocytic carcinomas. Archival formaldehyde-fixed, paraffin-embedded tumor
      samples and normal control thyroid tissues were arranged in arrays and analyzed
      by fluorescence in situ hybridization (FISH). We used pericentromeric or locus
      specific probes for chromosomes 1, 7, 8, 9, 11, 12, 17, 18, 22, and X as well as
      for the oncogenes Her2/neu, cyclin D1, N-myc, and c-myc. The average number of
      aneusomies per nucleus was significantly higher in carcinomas than in adenomas,
      and in both, monosomies were more frequent than polysomies. Loss of chromosome 22
      was found in 8 of 21 (38%) carcinomas; in 5 cases, it was associated with
      chromosome 2 monosomy. Conversely, chromosome 2 aberrations were not found in
      adenomas. Monosomies for chromosome 8 and X were detected in most adenomas and
      carcinomas. The most common gains in adenomas and carcinomas were for chromosome
      7 (13.8% and 32.0% of the cases, respectively), chromosome 12 (9.6% and 12.0%),
      and chromosome 17 (19.3% and 32.0%). None of the adenomas with trisomy 17 was
      associated with gains for chromosomes 7 and 12. None of the analyzed oncogenes
      was found to be amplified by FISH analysis. Our results indicate that numerical
      chromosomal aberrations in oncocytic follicular tumors of the thyroid gland are
      common findings and suggest that different patterns of aberrations may occur in
      these neoplasms.

PMID- 10923925
TI  - Stromelysin-3 expression in noninvasive and invasive neoplasms of the urinary
      bladder.
AB  - Stromelysin-3 (ST-3) is a protease frequently expressed by fibroblasts
      surrounding invasive carcinomas. Based on its expression in some cases of breast
      carcinoma-in-situ, it has been thought to indicate a higher likelihood for
      subsequent invasion in preinvasive lesions. Carcinoma-in-situ (pTis) and
      noninvasive papillary tumor (pTa) of the urinary bladder are preinvasive lesions
      with an uncertain potential to become invasive. We studied the expression of ST-3
      in pTis, pTa, and invasive bladder tumors to see whether it had an association
      with any established histopathologic variables and whether its expression might
      be an indicator of incipient invasion in the preinvasive lesions. Twenty-seven
      pTis, 27 pTa tumors, and 56 invasive bladder carcinomas were studied for ST-3
      expression with immunohistochemistry and, in selected cases, with in situ
      hybridization. Staining for ST-3 was evaluated semiquantitatively. None of 27
      pTis lesions, 4 of 27 pTa tumors, and 41 of 56 (73.2%) invasive carcinomas were
      positive for ST-3. Statistically significant associations were found in the
      invasive carcinomas between ST-3 expression and lymphatic vessel invasion, an
      infiltrative invasive pattern, and invasion into at least the muscle layer
      (pT2,3,4 v pT1). The expression of ST-3 in frankly invasive tumors was associated
      with a more aggressive tumor phenotype. Its expression in a small subgroup of pTa
      lesions may be indirect evidence that some tumors diagnosed as pTa have invasive
      potential.

PMID- 10923926
TI  - Cytopathic effect of in situ gene therapy in prostate cancer.
AB  - This is a morphologic study of in situ gene therapy effects in patients with
      prostate cancer using the Herpes Simplex VirusThymidine Kinase gene (HSV-tk)
      followed by ganciclovir. Prostatectomy specimens from the first 4 patients showed
      the following morphologic changes: (1) various degrees of necrosis were seen in
      cancer foci; (2) cytopathic changes were seen across the whole spectrum of
      Gleason grades; (3) the normal prostate was rarely affected by necrosis, but
      contained an intense mononuclear infiltrate; (4) loss of nuclear detail was a
      common finding. Volumetric studies showed that only portions of the tumor show
      morphologic effects as well as an inverse relationship between percentage of
      affected tumor and prostate and tumor size. An inflammatory response was
      observed, with predominance of CD20-positive cells in normal prostate tissue, CD8
      (cytotoxic T cells) in the tumor, and macrophages in all areas of the treated
      prostates. We believe that these changes represent the cytopathic effect of our
      in situ gene therapy on prostate cancer, and that they trigger a local immune
      response.

PMID- 10923927
TI  - Common-variable immunodeficiency-related lymphomas associate with mutations and
      rearrangements of BCL-6: pathogenetic and histogenetic implications.
AB  - Common-variable immunodeficiency (CVI) patients develop non-Hodgkin's lymphomas
      (NHL), mainly B-lineage diffuse large-cell lymphomas (DLCL), with a high relative
      risk. The molecular pathogenesis of CVI-related NHL (CVI-NHL) is unknown. Here we
      aimed at providing a detailed molecular characterization of CVI-NHL.
      Rearrangements of BCL-6 were detected in two thirds of CVI-NHL cases examined.
      All 3 CVI-NHL also harbored point mutations of the BCL-6 5' noncoding regions,
      which constitute a marker of B-cell transit through the germinal center (GC). The
      number and molecular pattern of BCL-6 mutations in CVI-NHL were similar to that
      detected in DLCL of immunocompetent hosts and in DLCL arising in other
      immunodeficiency settings. Microsatellite instability occurred in one CVI-NHL
      devoid of a BCL-6 rearrangement. All CVI-NHL scored negative for genetic lesions
      of BCL-2, p53, c-MYC, REL as well as for viral infection by EBV and HHV-8.
      Overall, these data indicate that: similarly to other immunodeficiency-related
      NHL, involvement of BCL6 occurs frequently also in CVI-NHL; and because BCL-6
      mutations are acquired by B cells during GC transit, their occurrence in CVI-NHL
      suggest that these lymphomas are histogenetically related to GC B cells.

PMID- 10923929
TI  - Lipid-rich diffuse malignant mesothelioma: a case report.
AB  - An 80-year old man presented with shortness of breath and was found to have a
      large right pleural effusion. Cytology of the pleural fluid showed atypical
      papillary clusters of epithelioid cells. Multiple white-yellow nodules studding
      the pleural surfaces were seen at thoracoscopy, and biopsies showed solid and
      papillary clusters of large epithelioid cells with abundant cytoplasm filled with
      clear vacuoles. Special stains and electron microscopic findings indicated that
      the tumor was a diffuse malignant mesothelioma with numerous intracytoplasmic
      lipid vacuoles. Fat stain may be useful at time of frozen section for a pleural
      based tumor with vacuolated cells, and the presence of lipid vacuoles in a
      pleural-based tumor does not exclude diffuse malignant mesothelioma.

PMID- 10923928
TI  - Hepatocellular carcinoma and focal hepatic glycogenosis after prolonged
      azathioprine therapy.
AB  - A 22-year-old woman without predisposing liver disease developed focal hepatic
      glycogenosis and hepatocellular carcinoma after 6 years of azathioprine therapy
      for Crohn's disease. Hepatocellular carcinoma without cirrhosis has previously
      been described during immunosuppression, but this is the first report of
      disseminated focal hepatic glycogenosis after long-term azathioprine therapy.

PMID- 10923930
TI  - Angiotropic large-cell lymphoma presenting as pulmonary small vessel occlusive
      disease.
AB  - Angiotropic lymphoma (AL) is an unusual variant of extranodal lymphoma,
      characterized by massive proliferation of neoplastic lymphoid cells almost
      exclusively within blood vessels. Whereas the lymphoid origin of this disease is
      widely accepted it still remains unclear whether AL is a distinct entity that
      originates in the blood vessels or whether it represents a form of secondary
      intravascular dissemination of a primary solid lymphoma. The present case is
      unusual because death by right heart failure owing to extensive intravascular
      proliferation of neoplastic cells and subsequent occlusion of pulmonary blood
      vessels has not been described so far. In addition, the patient had suffered from
      a solid deposit of a large-cell B-lymphoma months before the angiotropic
      manifestation, suggesting that AL might develop out of more common types of non
      Hodgkin's lymphomas.

PMID- 10923931
TI  - Adenoma of the pigmented ciliary epithelium: ultrastructural and
      immunohistochemical findings.
AB  - We report the clinical and histological findings in a tumor of the pigmented
      ciliary epithelium. The tumor was detected because it had caused a unilateral
      cataract, and it was removed by local resection because a malignant melanoma
      could not be excluded. The diagnosis was established by light microscopy, and
      additional immunohistochemical and detailed ultrastructural studies were
      performed. The so-called foam cells which are considered typical of these
      adenomas appear to be mostly light microscopic artifacts and had no
      ultrastructural equivalent in the sections examined from our tumor. Our results
      also strongly support the hypothesis that no true glandular elements are formed
      and that, apart from the neoplastic tissue architecture, most of the pathological
      findings are related to melanosomes.

PMID- 10923932
TI  - Confirmation of a diagnosis of synovial sarcoma in an unusual site.

PMID- 10923933
TI  - Fundic gland polyps: do they arise as a by-product of hypergastrinemia in
      patients with Zollinger-Ellison syndrome?

PMID- 10923934
TI  - Audiovestibular findings and location of an acoustic neuroma.
AB  - Forty-one patients with unilateral acoustic neuroma (AN) were diagnosed by
      magnetic resonance imaging (MRI) between 1992 and 1997. All cases were analyzed
      with respect to tumor location and the results of audiometric examinations,
      auditory brainstem response (ABR) testing, and electronystagmography (ENG). Tumor
      location was determined by MRI and cases were divided into intracanalicular and
      extracanalicular sites. Intracanalicular tumors were significantly smaller than
      the extracanalicular ones The pure-tone hearing thresholds were better in ears
      with intracanalicular lesions than in those with extracanalicular ones.
      Respectively, speech reception thresholds were 33 dB and 45 dB, and speech
      discrimination scores 79% and 65%. ABR was abnormal in 98% of ANs, but was
      insufficient for determining tumor location. The ENG pursuit test was more
      frequently normal and the caloric side difference was smaller in ears with
      intracanalicular than extracanalicular AN. These findings show that the results
      of pure-tone and speech audiometry and ENG are better in ears with
      intracanalicular AN, while ABR results are similar regardless of tumor location.

PMID- 10923935
TI  - Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in the
      nasal mucosa of patients with rhinitis.
AB  - Since nitric oxide (NO) can be involved in multiple physiological and
      pathological functions, we evaluated its possible involvement and that of
      peroxynitrite in the pathogenesis of rhinitis. Inferior nasal turbinates were
      obtained from allergic rhinitis and nonallergic rhinitis patients during
      corrective nasal surgery. The expressions of the inducible form of nitric oxide
      synthase (iNOS) and the production of peroxynitrite and its metabolite 3
      nitrotyrosine were examined by immunohistochemistry in consecutive tissue
      sections. Each section (or tissue compartment) was given a score of 0-4 according
      to the labeling intensity seen, with the highest number representing the highest
      labeling intensity. The results showed that iNOS expression was present mainly in
      the mucosal epithelium, vascular endothelium, and submucosal glands. A
      significant difference was only observed in the labeling scores of glandular
      tissues of the allergic group, which had a higher iNOS labeling score. We also
      found that sections with a higher iNOS level did not necessarily exhibit a higher
      3-nitrotyrosine labeling intensity. These data suggest that iNOS-derived NO may
      have a role in the pathophysiology of rhinitis, especially the glandular function
      of allergic nasal mucosa. Moreover, our findings suggest that the production of
      peroxynitrite in rhinitis patients is not dependent on the level of iNOS alone.

PMID- 10923936
TI  - A survey of contemporary management of frontal sinus disease in the United
      Kingdom.
AB  - Surgery for frontal sinus disease historically has required an external approach.
      With the advent of endoscopic sinus surgery, endoscopic treatment for various
      frontal sinus pathologies has been described. This survey examined how widespread
      the use of endoscopy in frontal surgery has become. We were interested both in
      the acute emergency situation and in the more chronic situations such as
      mucocoeles. The replies of 266 practising United Kingdom surgeons to a postal
      questionnaire were evaluated. While 45% of surgeons regularly practise functional
      endoscopic sinus surgery (FESS), approximately 25% would attempt endoscopic
      drainage of acute frontal sinusitis and most perform an external trephine. Most
      surgeons also rely on external approaches to manage mucocoeles or pyocoeles
      (54%), although some (39%) attempt endoscopic drainage if the cyst lies
      sufficiently medially. Even with recurrent or intractable disease one-third
      attempt endoscopic surgery. When external surgery is used in the United Kingdom,
      only a small number of surgeons favour obliteration.

PMID- 10923937
TI  - Advantages of measuring air flow in the pharynx with internal thermistors.
AB  - The measurement of air flow in patients suffering from breathing disturbances
      during sleep is usually accomplished by an oro-nasal thermistor located at the
      upper lip. The detection of hypopneas using this system may be difficult because
      the external thermistor may be unable to differentiate between high and low air
      flow rates. To improve the diagnosis of hypopneas we introduced a new method
      using internal thermistors contained in the same tube and using the same sensors
      as when recording pressures in the upper airways for localization of obstructions
      and measuring the respiratory work. The internal thermistors/pressure transducers
      (Camtip) were contained in a silicone tube that had a 1.9-mm external diameter.
      Standard polysomnography was performed, and internal flow and estimated volume
      were included in the polysomnographic setup. Ten consecutive hypopneas were
      studied in six patients having sleep-related breathing disorders. Preliminary
      results indicate that this method of monitoring air flow is more sensitive to
      minor changes in air flow than the external thermistor. It also simplifies the
      detection of hypopneas. Our findings shows that measuring air flow by internal
      thermistors is better than that of external devices to monitor tidal air flow.
      The internal sensors also facilitate the diagnosis of hypopneas in patients with
      sleep-related breathing disorders. Determinations of temperature changes and
      airway pressure in the pharynx can also be performed by the same sensors. Hence,
      no additional equipment is necessary for flow tracings when pressure recordings
      are used in the PSG setup.

PMID- 10923938
TI  - Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute
      sinusitis in children.
AB  - We investigated the clinical value of intranasal budesonide in acute sinusitis in
      52 children with acute maxillary sinusitis. We randomly divided them into two
      groups: group 1 received oral pseudoephedrine (2 x 30 mg) and cefaclor (40 mg/kg)
      for 10 days, and group 2 received intranasal budesonide (2 x 100 microg) and
      cefaclor (40 mg/kg) for 10 days. Symptoms of headache, cough, and nasal
      stuffiness and signs of nasal discharge were graded before and after treatment.
      The patients whose symptoms and signs completely normalized after treatment were
      considered to have recovered, and those with persisting symptoms and signs after
      treatment as having not recovered. The results of the two treatment groups were
      compared. The recovery rate of the children in group 2 were significantly higher
      than those in group 1 (P < 0.05). No adverse drug effects were determined during
      the study period. These findings suggest that topical steroids may be a useful
      adjunctive agent in the treatment of acute sinusitis of children without apparent
      side effects and can possibly hasten the resolution of symptoms.

PMID- 10923939
TI  - Malignant fibrous histiocytoma of the larynx after radiotherapy for squamous cell
      carcinoma.
AB  - A few cases of malignant fibrous histiocytoma (MFH) of the larynx have been
      reported to date. All ages may be affected, but the tumor is more prevalent in
      the sixth and seventh decade of life. We describe a case of MFH in a 71-year-old
      Italian man who 8 years before underwent a right cordectomy and radiotherapy for
      squamous cell carcinoma. Recurrent tumor was found to be MFH. The clinico
      pathological features of this tumor are presented and the possible relationship
      between radiotherapy and MFH discussed. The neoplasm was characterized by spindle
      shaped atypical cells arranged in a diffuse storiform pattern. Mitoses were
      prominent, numerous, and often atypical. Immunohistochemically, neoplastic cells
      were strongly positive for vimentin and alpha1-antichymotrypsin but were negative
      for cytokeratins and S-100 protein. These findings confirmed the diagnosis and
      excluded possible sarcomatoid carcinoma, inflammatory pseudotumor, and a new
      carcinosarcoma. The risk of sarcoma after radiotherapy for squamous cell
      carcinoma in the larynx is very low when considering the frequent use of
      radiotherapy, but long follow-ups are required.

PMID- 10923940
TI  - Current advances in the basic research and clinical management of juvenile-onset
      recurrent respiratory papillomatosis.
AB  - Juvenile-onset recurrent respiratory papillomatosis is a relatively uncommon
      disease that presents clinically with symptoms ranging from hoarseness to severe
      dyspnea. Human papilloma viruses type 6 and 11 are important in the etiology of
      the papillomata and are most probably transmitted from mother to child during
      childbirth. Although spontaneous remission is frequent, a rare fatal course
      because of pulmonary spread or malignant transformation has occurred. CO2 laser
      evaporation of papillomas and adjuvant drug therapy using lymphoblastoid alpha
      interferon are the most common treatment modalities at present. However, several
      other treatment modalities have been tried with varying success. Recent advances
      in basic research and different therapeutic approaches are reviewed.

PMID- 10923941
TI  - A solitary manifestation of mastocytosis in the head and neck.
AB  - Solitary mastocytosis in adulthood is a rare finding. Only two such lesions have
      been reported in the head and neck. We describe a 27-year-old woman who had a 10
      year history of a forehead swelling that had fluctuated in size. Light trauma or
      pressure on the lesion resulted in an increase in its size. A mass was found to
      be situated just below the galea and was successfully removed surgically using a
      high forehead lift. Histologically, the specimen contained predominantly mast
      cells. A systemic mastocytosis was excluded by a multidisciplinary diagnostic
      approach and measurement of the 24-h urinary excretion of histamine metabolites.
      After 36 months of follow-up there has been no recurrence.

PMID- 10923942
TI  - Temporal bone findings in multiple endocrine neoplasia type 2B.
AB  - To our knowledge, present case is the first published report of temporal bone
      findings in multiple endocrine neoplasia type 2B (MEN-2B). We describe a 43-year
      old Japanese man with medullary thyroid carcinoma (MTC), pheochromocytoma,
      mucosal neuroma and a Marfanoid body habitus. The collateral adrenal tumors and
      MTC were removed surgically. However, 14 years after surgery, the MTC and
      pheochromocytoma recurred and the patient died of intracranial hemorrhage due to
      hypertension. During the autopsy, metastatic MTC was detected in the liver,
      lungs, kidneys, pancreas and cervical lymph nodes. Recurrent pheochromocytoma was
      present in the right kidney. Mucosal neuromas were found in the tongue,
      gastrointestinal tract and vesical nerve plexus. The following histopathological
      findings were seen in both temporal bones: metastatic MTC was found as well as
      neuromas and the cochlear aqueduct was widely patent.

PMID- 10923943
TI  - Combined use of endoscopic CO2 laser excision of a marginal laryngeal tumor,
      radical neck dissection, and perioperative laterofixation of the opposite vocal
      cord.
AB  - We report the use of endoscopic laser excision of a marginal laryngeal tumor,
      radical neck dissection, and laterofixation of a paralyzed vocal cord in a 66
      year-old man who had an early-stage right supraglottic endolaryngeal tumor and
      ipsilateral neck metastasis. He had a left vocal cord paralysis after a left
      pneumonectomy that was performed 5 years previously. The primary laryngeal tumor
      was excised by endoscopic CO2 laser resection, and a simultaneous radical neck
      dissection was carried out. Postoperatively, severe inspiratory dyspnea developed
      because of the surgical intervention on the right side causing moderate laryngeal
      edema and limited movement of the right vocal cord in addition to the paralyzed
      left side. An endolaryngeal laterofixation of the paralyzed left vocal cord was
      performed to provide the patient with an adequate airway instead of tracheostomy.
      This patient had a 2 years' follow-up without recurrence of tumor. In the
      meantime movement of the right vocal cord has returned, so that the patient's
      voice was socially acceptable and he has a functioning larynx.

PMID- 10923944
TI  - Induction chemotherapy by superselective intra-arterial high-dose carboplatin
      infusion for head and neck cancer.
AB  - To evaluate the feasibility, maximum dose of drug tolerated, technical problems,
      systemic and local toxicity, response rate, overall and disease-free survival, we
      studied superselective intra-arterial infusion of high-dose carboplatin as part
      of a multimodality treatment for head and neck cancer. Forty patients with
      untreated stage II-IV head and neck squamous cell carcinomas received induction
      chemotherapy with high-dose carboplatin (three cycles at 2-week intervals using
      300-350 mg/m2 per cycle), delivered via superselective transfemoral angiography
      followed by radiotherapy or surgery plus radiotherapy. No technical complications
      occurred during or after the infusion. Systemic toxicity was minimal, and local
      toxicity was moderate. At the end of chemotherapy the overall complete and
      partial response rate was 90% (36/40) at the primary site and 64% (16/25) at the
      neck nodes. The median follow-up was 24.4 months (range 3-52). To date 21
      patients are alive without disease, 2 are alive with disease, 13 have died of
      disease, and 4 have developed a metachronous lung tumor. There was a good
      correlation between the response to chemotherapy and disease-free survival. No
      statistically significant benefit in survival was observed with respect to other
      series of head and neck tumors treated with different protocols. However,
      discriminating between responding and nonresponding patients, this procedure can
      have a prognostic significance in planning integrated treatments for these types
      of tumors.

PMID- 10923945
TI  - Submandibular approach for excision of a large schwannoma in the base of the
      tongue.
AB  - A 24-year-old Turkish woman is described, who gradually developed progressive
      swallowing problems over 6 months due to a tumor in the base of the tongue.
      Magnetic resonance imaging showed a large well-circumscribed solid mass.
      Histopathological examination of an incisional biopsy showed a schwannoma. The
      tumor was completely removed through a submandibular approach. The postoperative
      course was uneventful and her complaints disappeared. The submandibular approach
      used gave an excellent exposure of the base of tongue with a less obvious scar
      than a lip-splitting incision.

PMID- 10923946
TI  - Use of the carbon dioxide laser for tracheobronchial pathology in children.
AB  - The carbon dioxide (CO2) laser has been used to treat tracheobronchial pathology
      for more than 20 years. It was initially employed in adults and now has been
      found to be useful in the treatment of certain lesions in children. We present
      our experience with this technique in 30 patients treated with a CO2
      bronchoscopic laser from 1987 to 1995 in the Ear, Nose, and Throat Department of
      Armand Trousseau Hospital. Four different types of pathologies have been
      successfully treated with the laser: selective cases of tracheobronchial stenosis
      following trauma and/or secondary to neonatal ventilation, posttraumatic
      tracheobronchial granuloma (due to foreign bodies or tracheotomies),
      tracheobronchial granulomas of infectious origin (tuberculosis), and selective
      cases of tracheobronchial tumor.

PMID- 10923947
TI  - Interleukin-12 related cytokine gene expression at a tissue level in carcinomas
      of the larynx.
AB  - Head and neck squamous cell carcinomas are highly immunogenic tumors in which
      tumor-infiltrating lymphocytes (TIL) consist largely of CD4, Th1, and Th2
      lymphocytes and a minor proportion of other immune effector cells, such as
      macrophages and B cells. Interleukin (IL)-12 release and antigen presentation
      from macrophages induce Thl and Th2 differentiation. Gene expression for IL-12,
      interferon (IFN)gamma, IL-4, and other cytokines was studied by reverse
      transcriptase-polymerase chain reaction in tissue sections from laryngeal
      carcinomas to evaluate the mechanisms of Th1 and Th2 lymphocyte differentiation.
      Local effects of cytokines were probed evaluating immunohistochemically the
      presence of inducible nitric oxide synthase positive tumor-infiltrating
      macrophages in 13 cases of laryngeal carcinomas. IL-12 gene expression was
      observed in five cases and that for IFNgamma in nine cases. These cytokines were
      coexpressed in four specimens. IL-4 and transforming growth factor-beta1 were
      detected in 5 and 11 cases, respectively. These findings show that IL-12,
      IFNgamma, IL-4, and IL-6 in laryngeal carcinomas have different patterns of gene
      expression, suggesting distinct pathways of Th1 and Th2 lymphocyte
      differentiation to indicate that their exogenous modulation might be utilized in
      adoptive immunotherapy.

PMID- 10923948
TI  - Actinic keratosis is squamous cell carcinoma.
AB  - BACKGROUND: The prevalence of nonmelanoma skin cancer in the United States is
      alarming. It can be most appropriately treated if the earliest manifestation of
      cutaneous squamous cell carcinoma is recognized. METHODS: Clinical, histologic,
      and molecular biology, considerations were reviewed to determine whether actinic
      keratosis is the earliest clinical manifestation of cutaneous squamous cell
      carcinoma. RESULTS: The clinical, histologic, and molecular parameters of actinic
      keratosis are those of squamous cell carcinoma. CONCLUSION: Actinic keratosis
      does not transform, convert, or progress into cutaneous squamous cell carcinoma
      but is the earliest clinically recognizable manifestation of this malignancy.

PMID- 10923950
TI  - Transcatheter arterial embolization in blunt hepatic trauma.
AB  - Patients with blunt hepatic injury can safely be managed nonoperatively if they
      show hemodynamic stability. Transcatheter arterial embolization (TAE) is a useful
      adjunct in the treatment of patients who show evidence of continued hemorrhage or
      who have pooling of contrast material on computed tomography (CT). In these
      patients, TAE may reduce transfusion requirements and allow healing of the injury
      without operation. Complications are uncommon and are usually managed
      nonoperatively.

PMID- 10923949
TI  - Male pattern baldness.
AB  - BACKGROUND: Male pattern baldness, or androgenetic alopecia (AGA) in men, occurs
      with varying severity and age of onset. Two new treatments widely available as
      alternatives to 2% minoxidil are 1 mg finasteride and topical 5% minoxidil.
      Finasteride is a 5 alpha-reductase inhibitor available by prescription only; 5%
      minoxidil is available over the counter. METHODS: We searched MEDLINE to identify
      all articles on AGA and its pharmacologic therapies. RESULTS: We found limited
      information on AGA in peer review medical journals. Associated diseases include
      psychologic disorders and coronary heart disease. Hair growth is unpredictable
      and limited for all pharmacologic therapies, with the vast majority of treatment
      studies being industry sponsored. CONCLUSION: AGA is not easy to treat.
      Finasteride and 5% minoxidil offer new therapeutic options to the balding man.
      Treatment options may improve as new drugs are further investigated.

PMID- 10923951
TI  - Neurocysticercosis.

PMID- 10923952
TI  - Munchausen by Internet: detecting factitious illness and crisis on the Internet.
AB  - Within the past few years, the Internet has exploded into a medium of choice for
      those interested in health and medicine. Along with the promise of immediate
      access to authoritative resources via websites, the Internet offers "virtual
      support groups" through formats such as chat rooms and newsgroups. These person
      to-person exchanges, typically focusing on a specific topic, can be invaluable
      sources of information and compassion for patients and their families. However,
      individuals may misuse these Internet groups at times, offering false stories of
      personal illness or crisis for reasons such as garnering attention, mobilizing
      sympathy, acting out anger, or controlling others. I present four such cases and,
      based on experience with these and other cases of "virtual" factitious disorder
      and Munchausen by proxy, summarize indicators of factitious Internet claims and
      the reactions that participants usually experience once the ruse is recognized.

PMID- 10923953
TI  - Right ventricular alterations in scuba divers: findings on electrocardiography
      and echocardiography.
AB  - BACKGROUND: Scuba diving imposes uncommon environmental stresses. This study
      assesses the effects of recreational scuba diving on the electrocardiogram (ECG)
      and echocardiogram and compares them with those of normal controls. METHODS: We
      studied 50 recreational scuba divers and 50 age-matched and sex-matched normal
      control subjects. Each subject had a medical history, physical examination,
      resting 12-lead ECG, and transthoracic echocardiogram. RESULTS:
      Electrocardiographic findings occurring significantly more frequently in scuba
      divers than in controls were sinus bradycardia, sinus arrhythmia, QRS duration (>
      or = 0.10 sec, right axis duration and R > or =S in V2. The mean right
      ventricular internal dimension (RVID) was significantly larger in divers than in
      controls. High-normal RVID (2.0 to 2.3 cm) occurred significantly more regularly
      in divers than in controls (10 vs 1). CONCLUSION: Recreational scuba diving
      produced right ventricular alterations characterized by chamber dilation and
      electrocardiographic signs of right ventricular hypertrophy, sinus bradycardia,
      and arrhythmia.

PMID- 10923954
TI  - Acute care of patients aged 95 to 99 years: experience in a community teaching
      hospital.
AB  - BACKGROUND: People older than 90 years represent an increasing segment of the US
      population, but little information exists on their hospitalization for acute
      illness. METHODS: We retrospectively analyzed the clinical characteristics of
      patients aged 95 through 99 years admitted during 1 year to a large teaching
      hospital. RESULTS: Of 43 patients admitted at least once, 14 were admitted twice,
      6 were admitted three times, and 1 was admitted four times; 35 (81%) were women,
      and 8 (19%) were men. Patients admitted more than once took a mean of 6.8 +/- 3.3
      drugs compared with 4.4 +/- 2.6 drugs for patients admitted only once. Routine
      laboratory values were typically normal or mildly abnormal. Mean hospitalization
      was 5.6 +/- 3.5 days. Only 2 patients (5%) died. All 11 patients with a recent
      fall were discharged to a long-term nursing facility, compared with only 18 of 30
      patients without a recent fall. CONCLUSIONS: Patients aged 95 through 99 years
      generally have a favorable prognosis when hospitalized for an acute medical
      condition. However, patients with a recent fall are more likely to require
      placement in a long-term nursing facility, and patients taking six or more drugs
      on admission are more likely to be rehospitalized within 12 months.

PMID- 10923955
TI  - Positive urine nitrite test: an accurate predictor of absence of pure
      enterococcal bacteriuria.
AB  - BACKGROUND: The aim of this study was to determine the potential ability of the
      urine nitrite test (NT) to predict the class of organism causing urinary tract
      infection. METHODS: We retrospectively reviewed the records of all adult patients
      with a positive urine culture over a 6-month period. The infecting microorganisms
      and the urine NT results were recorded. RESULTS: A total of 729 positive cultures
      met inclusion criteria. Twenty-one (11%) of the 190 gram-positive organisms and
      199 (46%) of the 429 gram-negative organisms yielded a positive NT. Only 5.3% of
      samples with pure growth of enterococcus yielded a positive NT. The predictive
      value that a sample yielding a positive NT would show pure growth of enterococcus
      was low at 2.3%. CONCLUSION: A positive NT is highly predictive of the absence of
      pure enterococcal bacteriuria.

PMID- 10923956
TI  - Is the leak test reproducible?
AB  - BACKGROUND: The leak test is an accepted practice for evaluating airway edema and
      patient readiness for extubation. Reproducibility and interobserver reliability
      for this test have not been established. We studied the reproducibility and
      reliability of the leak test in and among health care professionals. METHODS:
      Thirteen consecutive intubated patients were tested in triplicate and in blinded
      fashion by three observers to determine the leak around the endotracheal tube
      before extubation. All patients were pharmacologically paralyzed and sedated
      before assessment. RESULTS: Neither interobserver or intraobserver variability
      was statistically significant when a standardized method was used to determine
      the leak. CONCLUSION: The leak test is reliable by the same or different
      observers regardless of varied clinical experience when using a standardized
      approach to measuring the leak.

PMID- 10923957
TI  - Increasing maternal weight: a risk factor for preeclampsia/eclampsia but
      apparently not for HELLP syndrome.
AB  - BACKGROUND: Maternal obesity is a risk factor for severe preeclampsia. We sought
      to ascertain whether a similar relationship exists between maternal weight and
      HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets) as an
      atypical form of severe preeclampsia. METHODS: In this retrospective
      investigation, 434 patients with HELLP syndrome were assigned to one of four
      study groups according to maternal weight and were analyzed in relation to
      selected maternal and perinatal data reflective of disease severity. RESULTS: We
      found no significant associations between maternal weight and parameters of HELLP
      syndrome severity, race, delivery mode, gestational age, or perinatal outcome.
      Significantly associated with increasing maternal weight were maternal age,
      parity, admission mean arterial pressure, peak peripartum systolic blood
      pressures, concurrent essential hypertension, and the interval between admission
      and delivery. Inversely associated were eclampsia and the interval between
      delivery and discharge. CONCLUSIONS: Severity and complications attendant with
      HELLP syndrome appear unrelated to maternal weight. Paradoxically, eclampsia
      occurs most commonly in the lighter gravida with HELLP syndrome.

PMID- 10923959
TI  - Biliary cystadenoma: rare variant of intrahepatic cystic disease.
AB  - Intrahepatic nonparasitic cystic disease is rare and may be of congenital or
      neoplastic origin. The most frequent symptoms and signs are nonspecific and
      include pain, nausea, fullness, increased girth, and palpable mass.
      Interventional therapy is reserved for symptomatic patients, which usually
      corresponds to cysts >5 cm in diameter. Retrospective analysis revealed 26 cases
      of intrahepatic cystic disease over 15 years at our institution. We discuss the
      case of a patient who had bilobular biliary cystadenomatous disease, a rare,
      benign variant of intrahepatic nonparasitic cystic disease.

PMID- 10923958
TI  - Utility of bone marrow biopsy for rapid diagnosis of febrile illnesses in
      patients with human immunodeficiency virus infection.
AB  - BACKGROUND: Histochemical staining of bone marrow biopsy samples for
      microorganisms may provide a presumptive diagnosis weeks before culture. METHODS:
      To identify predictors of histochemical positivity, we reviewed 161 bone marrow
      biopsies from febrile patients with human immunodeficiency virus (HIV) infection.
      RESULTS: By multivariate analysis, both hematocrit value <30% and white blood
      cell count <4,000/mm3 predicted biopsy positivity by culture or staining, but
      only anemia predicted histochemical stain positivity. Of cases with serum lactate
      dehydrogenase (LDH) levels >600 U/L, histoplasmosis was diagnosed in 31.6% versus
      7.8% with lower LDH levels. Among histoplasmosis cases, staining showed fungi in
      all, with LDH levels >600 U/L versus 44.4% with lower levels. CONCLUSIONS: Bone
      marrow biopsy will most likely provide a rapid diagnosis in patients with anemia.
      Markedly elevated LDH levels suggest stain positivity for Histoplasma capsulatum.
      Histopathologic patterns may also guide empiric therapy.

PMID- 10923960
TI  - Hyperthyroidism after hypothyroidism.
AB  - The development of hyperthyroidism after primary hypothyroidism is unusual. We
      report such a case in a 37-year old man and review the clinical and immunologic
      aspects of the previously published cases of 50 female and 19 male patients with
      a similar condition.

PMID- 10923961
TI  - Bacteremia and possible endocarditis caused by Moraxella phenylpyruvica.
AB  - Moraxella phenylpyruvica, a gram-negative coccobacillus, is usually considered a
      nonpathogenic bacterium. Only a few cases of invasive disease caused by this
      organism were reported in the 1970s. We report a well-documented case of
      bacteremia and possible endocarditis due to M phenylpyruvica in a previously
      healthy man.

PMID- 10923962
TI  - Diagnosis of polycythemia vera in an anemic patient.
AB  - Criteria proposed by the Polycythemia Vera Study Group (PVSG) as well as several
      derived algorithms are currently used for the diagnosis of polycythemia vera.
      Although these guidelines have significantly enhanced diagnostic accuracy, they
      uniformly consider erythrocytosis as the requisite premise for instigating the
      subsequent workup. We describe the unusual presentation of a patient with
      microcytic anemia in whom the diagnosis of polycythemia vera was reached using
      the PVSG criteria and confirmed by in vitro culture assay of erythroid progenitor
      cells. This case highlights the usefulness of the PVSG criteria, including the
      red cell mass determination, for the diagnosis of polycythemia vera even in
      anemic patients. The roles of spleen red cell pooling and plasma volume expansion
      as major determinants of this unusual presentation are discussed.

PMID- 10923963
TI  - Extramammary Paget's disease.
AB  - Extramammary Paget's disease (EMPD) is an uncommon but distinctive tumor. The
      lesion is defined as an intra-epidermal neoplasm. The lesion may be accompanied
      by an invasive adenocarcinoma or in situ adenocarcinoma of apocrine glands.
      Visceral carcinoma may also coexist or develop. Definitive diagnosis requires
      biopsy of the lesion and immunohistochemical staining. In most cases of
      noninvasive or minimally invasive EMPD, surgical resection with clear margins and
      careful follow-up are recommended, since the recurrence rate is high. We review
      the literature and report two cases of EMPD, one involving the perineal-scrotal
      area and the other involving the perianal area.

PMID- 10923964
TI  - Primary meningioma of the fallopian canal.
AB  - Meningiomas are slow-growing lesions that represent approximately 20% of all
      intracranial tumors and are the second most common tumor of the cerebellopontine
      angle. In contrast, primary extracranial meningiomas are found relatively
      infrequently, and most cases have inadequate radiologic studies to determine if
      they were actually an extension from a primary intracranial source. Meningiomas
      of the intratemporal segment of the facial nerve have also been reported, but
      they are exceedingly rare and their pathophysiology remains unclear. We report a
      case of a meningioma of the facial nerve in the fallopian canal of a 7-year-old
      girl and review pertinent literature.

PMID- 10923965
TI  - Amniotic fluid embolism.
AB  - Amniotic fluid embolism is a rare occurrence, with no single pathognomonic
      clinical or laboratory finding. Diagnosis is based on clinical presentation and
      supportive laboratory values. We describe the case of a 17-year-old nulliparous
      woman at 27 weeks' gestation who had uterine bleeding, hematuria, hemoptysis,
      hypotension, dyspnea, and hypoxemia within 30 minutes of vaginal delivery.
      Laboratory values revealed diffuse intravascular coagulation. Chest films were
      consistent with adult respiratory distress syndrome. Pulmonary artery
      catheterization revealed moderately increased pulmonary capillary wedge pressure.
      Supportive measures, including oxygenation, fluid resuscitation, and plasma, were
      administered. Central hemodynamic monitoring and inotropic support were
      necessary. Our patient recovered uneventfully and 6 weeks later was living an
      unrestricted life-style.

PMID- 10923966
TI  - Paraplegia diagnosed by a new physical sign.
AB  - Clinical diagnosis is a process of logical deduction from the data gathered by
      history and physical examination. When organic causes of an illness have been
      ruled out, a diagnosis of "functional disorder" or "conversion reaction" is
      considered. Cost of care of such patients can be enormous, especially when a
      large number of investigations are done to find an organic illness, which does
      not really exist. In such cases, a positive and early diagnosis of a conversion
      reaction can save needless tests and much distress to the patient. This report
      describes a case of paraplegia that was investigated for years before a diagnosis
      of conversion reaction was firmly made, based on a novel observation. We believe
      that we describe here a new physical sign, which can be used to diagnose
      "hysterical paraplegia."

PMID- 10923967
TI  - Quinine-induced hemolytic-uremic syndrome.
AB  - Quinine is still frequently used by practitioners for the treatment of nocturnal
      leg cramps, despite the lack of Food and Drug Administration (FDA) approval. We
      report the 15th case of quinine-induced hemolytic-uremic syndrome (HUS) in the
      medical literature. The likely mechanism by which quinine induces HUS is via
      quinine-dependent antibodies to blood cellular constituents. These antibodies
      likely cause endothelial damage and the resultant nephropathy, microangiopathic
      hemolytic anemia, and thrombocytopenia that define HUS. Although there is no set
      guideline for the treatment of quinine-induced HUS, most authorities consider
      plasmapheresis as the standard of care, especially in severe cases. Our patient
      required the longest known treatment duration (16 plasmapheresis treatments over
      a 37-day period) for disease resolution. The prognosis of quinine-induced HUS is
      excellent, with no deaths reported in the literature.

PMID- 10923968
TI  - Massive left diaphragmatic separation and rupture due to coughing during an
      asthma exacerbation.
AB  - We report a case of herniation of abdominal contents into the left hemithorax in
      a patient hospitalized with an acute exacerbation of asthma accompanied by
      paroxysms of coughing. There was no history of trauma. We believe this is the
      first reported case of diaphragmatic rupture complicating an asthma exacerbation.
      We review clinical features, pathophysiology, diagnosis, and treatment of
      diaphragmatic rupture in its most common setting, trauma, and discuss its
      occasional "spontaneous" occurrence.

PMID- 10923969
TI  - Epidural catheters: the long and winding road.
AB  - Entrapment and knotting of epidural catheters has been described, as well as
      techniques for removal. Several cases of successful removal have been reported;
      however, significant resistance was encountered during removal. Following the
      techniques described previously, we successfully removed a knotted epidural
      catheter.

PMID- 10923970
TI  - Actinic keratosis: time to call a spade a spade.

PMID- 10923971
TI  - Five things oculoplastic surgeons should know about neurosurgery.

PMID- 10923972
TI  - Prognostic factors for survival in malignant melanoma of the eyelid skin.
AB  - PURPOSE: This study aimed to determine the prognostic factors for survival and
      disease-free interval for malignant melanoma of the eyelid skin. METHODS: This
      was a retrospective, nonrandomized, clinical review. Twenty-four patients with
      eyelid skin melanoma were identified through a search of the tumor registry at M.
      D. Anderson Cancer Center. Patients were treated between 1953 and 1994. The
      follow-up ranged from 3 to 18 years (mean = 9.6 years). Primary treatment in all
      cases entailed wide local excision of the tumor. Patients in whom regional lymph
      node metastasis developed underwent parotidectomy or neck dissection, with or
      without adjuvant chemotherapy or external beam radiation. Descriptive statistics
      were used to characterize the patients. Survival analysis in terms of disease
      free survival and recurrence-free survival was performed using age, sex, location
      of tumor (upper lid, lower lid, or both), histologic type of melanoma, Breslow
      thickness, and Clark's level as independent variables for survival. RESULTS: Age,
      sex, location, and the histologic type of tumor were not significant prognostic
      indicators for survival in this cohort. Clark's level > or = IV by itself was a
      statistically significant predictor of decreased survival. In addition, tumors
      with either Clark's level > or = IV or Breslow thickness > or = 1.5 mm were
      associated with increased mortality. CONCLUSION: Clark's level > or = IV or
      Breslow thickness > or = 1.5 mm are poor prognostic indicators for malignant
      melanomas of the eyelid skin. Clinicians should have a high level of suspicion
      for occult regional lymph node metastasis when treating patients with these tumor
      features.

PMID- 10923973
TI  - Secondary fractures of Le Fort I osteotomy.
AB  - PURPOSE: To report the ophthalmic complications of Le Fort I osteotomy for the
      correction of dentofacial deformities and to determine the maximal compressive
      loads applied during pterygomaxillary separation in a cadaver model. METHODS: Two
      cases of ophthalmic complications arising after Le Fort I osteotomy are reported.
      Le Fort I osteotomy was performed on five cadavers. The maximal compressive load
      applied during pterygomaxillary separation was recorded with a 10 kN (3,000 lbf)
      load cell of a MTS Mini-Bionix servo-hydraulic machine (MTS, Eden Prairie, MN,
      U.S.A.). A paired t test was used to compare forces applied to the right and left
      sides. Computed tomography scans of each specimen were obtained after Le Fort I
      osteotomy to document secondary fractures. The skulls were subsequently stained
      with 1% fuschin red to highlight secondary fractures. RESULTS: Maximum
      compressive loads during pterygomaxillary separation ranged from 22 N (5.0 lbf)
      to 162 N (36.5 lbf), with an average of 106 N (23.8 lbf) (SD 47.6 N [10.7 lbf]).
      Forces applied on the first operative side were significantly greater than forces
      applied on the second operative side (p = 0.0034). Secondary fractures were found
      in three specimens by computed tomography and in two specimens by 1% fuschin red.
      All secondary fractures occurred on the second operative side. CONCLUSION:
      Secondary fractures in the Le Fort I osteotomy procedures occurred on the side
      opposite the greater maximal compressive load and on the second operative side.

PMID- 10923974
TI  - Strabismus after balanced medial plus lateral wall versus lateral wall only
      orbital decompression for dysthyroid orbitopathy.
AB  - PURPOSE: This study aimed to determine the relative incidence and time course of
      new-onset strabismus after balanced medial plus lateral wall orbital
      decompression versus decompression of the lateral wall alone for dysthyroid
      orbitopathy. METHODS: The study design was a retrospective nonrandomized
      comparative case series. Thirty-two consecutive patients underwent balanced
      medial plus lateral wall orbital decompression or lateral wall orbital
      decompression for dysthyroid orbitopathy. The incidence, duration, and treatment
      of postoperative strabismus was recorded for each patient. RESULTS: Significant
      preoperative strabismus was present in 31% (4/13 patients) of the balanced
      decompression group and in 26% (5/19 patients) of the lateral wall decompression
      group. Only 25% (1/4) of cases of preexisting strabismus in the balanced
      decompression group resolved postoperatively without muscle surgery, whereas 60%
      (3/5) of cases in the lateral wall decompression group resolved postoperatively
      without surgery. Preoperative strabismus was absent in 69% (9/13) of patients in
      the balanced decompression group and in 74% (14/19) of patients in the lateral
      wall decompression group. New-onset, persistent postoperative strabismus
      developed in 33% (3/9) of patients in the balanced decompression group and in 7%
      (1/14) of patients in the lateral wall decompression group. CONCLUSION: Lateral
      wall orbital decompression may produce less new-onset, persistent postoperative
      strabismus than balanced medial plus lateral wall orbital decompression for
      dysthyroid orbitopathy.

PMID- 10923975
TI  - Hydroxyapatite implant wrapping materials: analysis of fibrovascular ingrowth in
      an animal model.
AB  - PURPOSE: To compare the influence of seven currently available spherical orbital
      implant wraps on host fibrovascularization of a hydroxyapatite (HA) orbital
      implant. METHODS: Five groups of 3 (15 total) adult male New Zealand albino
      rabbits underwent enucleation with placement of a 12-mm HA implant wrapped in
      high-porosity expanded polytetrafluoroethylene (e-PTFE), processed bovine
      pericardium, or processed human pericardium, sclera, or fascia lata. Magnetic
      resonance imaging before and after the intravenous administration of gadolinium
      diethylenetriamine pentaacetic acid (DTPA, 0.1 mol/kg) was performed immediately
      before exenteration. Five rabbits (one with each of the different implant wraps)
      were killed at 4, 8, and 12 weeks, and the operated socket was exenterated.
      Histopathologic sections of the implants were then compared with the results of
      our previous study using polyglactin 910 mesh and autologous sclera as HA orbital
      implant wraps. RESULTS: Complete fibrovascularization of all the implants
      occurred by 12 weeks; however, HA implants wrapped with sclera, polyglactin mesh,
      and e-PTFE appeared to undergo more rapid fibrovascularization than spheres
      wrapped with other materials. CONCLUSIONS: Although all of the implant wraps
      studied may be suitable substitutes for donor sclera, we prefer polyglactin mesh
      because it is readily available, inexpensive, and without risk of transmissible
      diseases.

PMID- 10923976
TI  - Polytetrafluoroethylene as a wrapping material for a hydroxyapatite orbital
      implant.
AB  - PURPOSE: Porous coralline hydroxyapatite orbital implants have been used with
      great success in anophthalmic sockets. We used a substitute for donor sclera as a
      wrapping tissue. METHODS: Orbital implants were wrapped with
      polytetrafluoroethylene (PTFE) instead of homologous donor tissue in five
      patients after enucleation. RESULTS: The postoperative course was uneventful in
      three cases. Complications occurred in two cases: one with implant exposure, and
      one with severe implant infection leading to its eventual removal. CONCLUSIONS:
      PTFE is inferior to other wrapping tissue.

PMID- 10923977
TI  - Treatment of Frey's syndrome (gustatory sweating) and 'crocodile tears'
      (gustatory epiphora) with purified botulinum toxin.
AB  - PURPOSE: To determine whether purified botulinum toxin might be as effective in
      the treatment of "crocodile tears" (gustatory epiphora) as it has been in the
      treatment of other hypersecretion syndromes such as Frey's syndrome (gustatory
      sweating). METHODS: One patient with Frey's syndrome (gustatory sweating) was
      successfully treated with botulinum toxin. After this, two patients with chronic
      symptomatic crocodile tears (related to previous facial palsy) were treated with
      botulinum toxin injections into and around the lacrimal gland. RESULTS: Both
      patients reported remarkable relief from symptoms and were observed to have no
      tearing while eating. CONCLUSIONS: Purified botulinum toxin appears to be an
      effective treatment for crocodile tears.

PMID- 10923978
TI  - Orbital Ewing's sarcoma of the orbit.
AB  - PURPOSE: Ewing's tumor is a primary tumor of bone in childhood that only rarely
      involves the orbit. Most such cases are metastatic from distant sites. This tumor
      may be confused with other small round cell malignancies of childhood, and
      immunohistochemical studies are essential in making the diagnosis. METHODS: We
      present two cases of Ewing's tumor of the orbit. One was in a 22-year-old boy
      with an occult primary tumor in the frontal bone that became symptomatic after
      forehead trauma. The other example was in a 7-year-old boy with a known Ewing's
      primary of the clavicle. The clinical manifestations and diagnostic criteria are
      discussed. RESULTS: In most cases with orbital involvement, ophthalmic symptoms
      consist of proptosis, pain, and occasionally visual loss and motility
      restriction. The diagnosis is typically unsuspected before histologic evaluation.
      Electron microscopic and immunohistochemical analyses are essential in making the
      diagnosis and are necessary for all such small round cell tumors. CONCLUSIONS:
      Ewing's sarcoma is a rare orbital tumor of bone mainly affecting children. Local
      treatment relying on surgical extirpation and radiotherapy alone has proven
      inadequate, with 5-year survival rates of <10%. The addition of chemotherapy has
      improved survival rates significantly to approximately 50%.

PMID- 10923979
TI  - Atypical presentation of a dacryolith.
AB  - PURPOSE: To describe the clinical features and management of a patient with an
      extralacrimal dacryolith. METHODS: Case report. RESULTS: A 43-year-old woman
      remarked at a routine eye examination that a small, firm mass located for several
      years on the right side of her nose had recently become slightly larger. The mass
      had remained firm and nontender during this enlargement. She explicitly denied
      having any past or current lacrimal outflow problems. Surgical excision disclosed
      a mass external to the lacrimal sac and duct, adherent to its lateral wall. The
      histopathologic features were consistent with a dacryolith surrounded by a
      chronic inflammatory reaction and no epithelial lining. CONCLUSION: We presume
      that the dacryolith must have formed within the lacrimal sac and then migrated
      laterally into the surrounding soft tissue.

PMID- 10923980
TI  - Second-degree eyelid burn after use of microwave-heated compress.

PMID- 10923981
TI  - Lacrimal drainage system stenting with silicone tubing.

PMID- 10923982
TI  - Trapdoor orbital fractures.

PMID- 10923983
TI  - Evolution of the basal ganglia: new perspectives through a comparative approach.
AB  - The basal ganglia (BG) have received much attention during the last 3 decades
      mainly because of their clinical relevance. Our understanding of their structure,
      organisation and function in terms of chemoarchitecture, compartmentalisation,
      connections and receptor localisation has increased equally. Most of the research
      has been focused on the mammalian BG, but a considerable number of studies have
      been carried out in nonmammalian vertebrates, in particular reptiles and birds.
      The BG of the latter 2 classes of vertebrates, which together with mammals
      constitute the amniotic vertebrates, have been thoroughly studied by means of
      tract-tracing and immunohistochemical techniques. The terminology used for
      amniotic BG structures has frequently been adopted to indicate putative
      corresponding structures in the brain of anamniotes, i.e. amphibians and fishes,
      but data for such a comparison were, until recently, almost totally lacking. It
      has been proposed several times that the occurrence of well developed BG
      structures probably constitutes a landmark in the anamniote-amniote transition.
      However, our recent studies of connections, chemoarchitecture and development of
      the basal forebrain of amphibians have revealed that tetrapod vertebrates share a
      common pattern of BG organisation. This pattern includes the existence of dorsal
      and ventral striatopallidal systems, reciprocal connections between the
      striatopallidal complex and the diencephalic and mesencephalic basal plate
      (striatonigral and nigrostriatal projections), and descending pathways from the
      striatopallidal system to the midbrain tectum and reticular formation. The
      connectional similarities are paralleled by similarities in the distribution of
      chemical markers of striatal and pallidal structures such as dopamine, substance
      P and enkephalin, as well as by similarities in development and expression of
      homeobox genes. On the other hand, a major evolutionary trend is the progressive
      involvement of the cortex in the processing of the thalamic sensory information
      relayed to the BG of tetrapods. By using the comparative approach, new insights
      have been gained with respect to certain features of the BG of vertebrates in
      general, such as the segmental organisation of the midbrain dopaminergic cell
      groups, the occurrence of large numbers of dopaminergic cell bodies within the
      telencephalon itself and the variability in, among others, connectivity and
      chemoarchitecture. However, the intriguing question whether the basal forebrain
      organisation of nontetrapods differs essentially from that observed in tetrapods
      still needs to be answered.

PMID- 10923984
TI  - Functional anatomy of movement disorders.
AB  - Models of basal ganglia function are described which encapsulate the principal
      pathophysiological mechanisms underlying parkinsonian akinesia on the one hand
      and abnormal involuntary movement disorders (dyskinesias) on the other. In
      Parkinson's disease, degeneration of the nigrostriatal dopamine system leads to
      overactivity of the 'indirect' striatopallidal projection to the lateral
      (external) segment of the globus pallidus. This causes inhibition of lateral
      pallidal neurons, which in turn project to the subthalamic nucleus. Disinhibition
      of the subthalamic nucleus leads to abnormal subthalamic overactivity and, as a
      consequence, overactivity of medial (internal) pallidal output neurons.
      Dyskinesias, such as are observed in Huntington's disease, levodopa-induced
      dyskinesia and ballism, share mechanistic features in common and are associated
      with decreased neuronal activity in both the subthalamic nucleus and the medial
      globus pallidus.

PMID- 10923986
TI  - Imaging basal ganglia function.
AB  - In this review, the value of functional imaging for providing insight into the
      role of the basal ganglia in motor control is reviewed. Brain activation findings
      in normal subjects and Parkinson's disease patients are examined and evidence
      supporting the existence for functionally independent distributed basal ganglia
      frontal loops is presented. It is argued that the basal ganglia probably act to
      focus and filter cortical output, optimising the running of motor programs.

PMID- 10923985
TI  - Synaptic organisation of the basal ganglia.
AB  - The basal ganglia are a group of subcortical nuclei involved in a variety of
      processes including motor, cognitive and mnemonic functions. One of their major
      roles is to integrate sensorimotor, associative and limbic information in the
      production of context-dependent behaviours. These roles are exemplified by the
      clinical manifestations of neurological disorders of the basal ganglia. Recent
      advances in many fields, including pharmacology, anatomy, physiology and
      pathophysiology have provided converging data that have led to unifying
      hypotheses concerning the functional organisation of the basal ganglia in health
      and disease. The major input to the basal ganglia is derived from the cerebral
      cortex. Virtually the whole of the cortical mantle projects in a topographic
      manner onto the striatum, this cortical information is 'processed' within the
      striatum and passed via the so-called direct and indirect pathways to the output
      nuclei of the basal ganglia, the internal segment of the globus pallidus and the
      substantia nigra pars reticulata. The basal ganglia influence behaviour by the
      projections of these output nuclei to the thalamus and thence back to the cortex,
      or to subcortical 'premotor' regions. Recent studies have demonstrated that the
      organisation of these pathways is more complex than previously suggested. Thus
      the cortical input to the basal ganglia, in addition to innervating the spiny
      projection neurons, also innervates GABA interneurons, which in turn provide a
      feed-forward inhibition of the spiny output neurons. Individual neurons of the
      globus pallidus innervate basal ganglia output nuclei as well as the subthalamic
      nucleus and substantia nigra pars compacta. About one quarter of them also
      innervate the striatum and are in a position to control the output of the
      striatum powerfully as they preferentially contact GABA interneurons. Neurons of
      the pallidal complex also provide an anatomical substrate, within the basal
      ganglia, for the synaptic integration of functionally diverse information derived
      from the cortex. It is concluded that the essential concept of the direct and
      indirect pathways of information flow through the basal ganglia remains intact
      but that the role of the indirect pathway is more complex than previously
      suggested and that neurons of the globus pallidus are in a position to control
      the activity of virtually the whole of the basal ganglia.

PMID- 10923988
TI  - NMDA receptors in the basal ganglia.
AB  - The basal ganglia consist of several interconnected nuclei located in the
      telecephalon, diencephalon and mesencephalon that are involved in a variety of
      motor and non-motor behavioural functions. Glutamate receptors play a major role
      in neurotransmission within the basal ganglia and are present in all nuclei of
      the basal ganglia. This review focuses on the contribution of the NMDA class of
      glutamatergic receptors to various movement disorders whose primary pathology
      lies within the basal ganglia and discusses how pharmacological manipulation of
      such receptors may be therapeutically useful.

PMID- 10923989
TI  - Dopamine and synaptic plasticity in the neostriatum.
AB  - After the unilateral destruction of the dopamine input to the neostriatum there
      are enduring changes in rat behaviour. These have been ascribed to the loss of
      dopamine and the animals are often referred to as 'hemiparkinsonian'. In the
      denervated neostriatum, we have shown that not only are the tyrosine hydroxylase
      positive boutons missing, but also the medium sized densely spiny output cells
      have fewer spines. Spines usually have asymmetric synapses on their heads. In a
      recent stereological study we were able to show that there is a loss of
      approximately 20% of asymmetric synapses in the lesioned neostriatum by 1 mo
      after the lesion. Current experiments are trying to establish the specificity of
      this loss. So far we have evidence suggesting that there is no obvious
      preferential loss of synapses from either D1 or D2 receptor immunostained
      dendrites in the neostriatum with damaged dopamine innervation. These experiments
      suggest that dopamine is somehow necessary for the maintenance of corticostriatal
      synapses in the neostriatum. In a different series of experiments slices of
      cortex and neostriatum were maintained in vitro in such a way as to preserve at
      least some of the corticostriatal connections. In this preparation we have been
      able to show that cortical stimulation results in robust excitatory postsynaptic
      potentials (EPSPs) recorded from inside striatal neurons. Using stimulation
      protocols derived from the experiments on hippocampal synaptic plasticity we have
      shown that the usual consequence of trains of high frequency stimulation of the
      cortex is the depression of the size of EPSPs in the striatal cell. In agreement
      with similar experiments by others, the effect seems to be influenced by NMDA
      receptors since the unblocking of these receptors with low Mg++ concentrations in
      the perfusate uncovers a potentiation of the EPSPs after trains of stimulation.
      Dopamine applied in the perfusion fluid round the slices has no effect but
      pulsatile application of dopamine, close to the striatal cell being recorded
      from, and in temporal association with the cortical trains, leads to a similar
      LTP like effect. The reduction of K+ channel conductance in the bath with TEA
      also has the effect of making cortical trains induce potentiation of
      corticostriatal transmission. TEA applied only to the cell being recorded from
      has no similar effect; the cortical stimulation again depresses the EPSP
      amplitude, so the site of action of TEA may well be presynaptic to the striatal
      cell. The morphological and physiological experiments may not necessarily be
      related but it is tempting to suggest that dopamine protects some corticostriatal
      synapses by potentiating them but that in the absence of dopamine others simply
      disconnect and are no longer detectable on electron microscopy.

PMID- 10923990
TI  - Aspects of PET imaging relevant to the assessment of striatal transplantation in
      Huntington's disease.
AB  - Proper assessment of outcome in clinical trials of neural transplantation
      requires both biochemical and imaging indices of graft survival, and behavioural
      and physiological indices of graft function. For transplantation in Huntington's
      disease, a variety of ligands that are selective for striatal degeneration and
      graft-derived replacement are available, notably ligands of dopaminergic
      receptors on striatal neurons. However, the validity of such ligands is
      potentially compromised by adjunctive drug therapies (e.g. neuroleptics) given to
      patients in the course of normal clinical care. We review the present state of
      experimental and clinical understanding of the selectivity of available ligands
      for striatal imaging, their interaction with other drug treatments, and
      strategies for refining valid assessment protocols in patients.

PMID- 10923987
TI  - GABA(B) and group I metabotropic glutamate receptors in the striatopallidal
      complex in primates.
AB  - Glutamate and GABA neurotransmission is mediated through various types of
      ionotropic and metabotropic receptors. In this review, we summarise some of our
      recent findings on the subcellular and subsynaptic localisation of GABA(B) and
      group I metabotropic glutamate receptors in the striatopallidal complex of
      monkeys. Polyclonal antibodies that specifically recognise GABA(B)R1, mGluR1a and
      mGluR5 receptor subtypes were used for immunoperoxidase and pre-embedding
      immunogold techniques at the light and electron microscope levels. Both subtypes
      of group I mGluRs were expressed postsynaptically in striatal projection neurons
      and interneurons where they aggregate perisynaptically at asymmetric
      glutamatergic synapses and symmetric dopaminergic synaptic junctions. Moreover,
      they are also strongly expressed in the main body of symmetric synapses
      established by putative intrastriatal GABAergic terminals. In the globus
      pallidus, both receptor subtypes are found postsynaptically in the core of
      striatopallidal GABAergic synapses and perisynaptically at subthalamopallidal
      glutamatergic synapses. Finally, extrasynaptic labelling was commonly seen in the
      globus pallidus and the striatum. Moderate to intense GABA(B)R1 immunoreactivity
      was observed in the striatopallidal complex. At the electron microscope level,
      GABA(B)R1 immunostaining was commonly found in neuronal cell bodies and
      dendrites. Many striatal dendritic spines also displayed GABA(B)R1
      immunoreactivity. Moreover, GABA(B)R1-immunoreactive axons and axon terminals
      were frequently encountered. In the striatum, GABA(B)R1-immunoreactive boutons
      resembled terminals of cortical origin, while in the globus pallidus, subthalamic
      like terminals were labelled. Pre-embedding immunogold data showed that
      postsynaptic GABA(B)R1 receptors are concentrated at extrasynaptic sites on
      dendrites, spines and somata in the striatopallidal complex, perisynaptically at
      asymmetric synapses and in the main body of symmetric striatopallidal synapses in
      the GPe and GPi. Consistent with the immunoperoxidase data, immunoparticles were
      found in the presynaptic grid of asymmetric synapses established by cortical- and
      subthalamic-like glutamatergic terminals. These findings indicate that both GABA
      and glutamate metabotropic receptors are located to subserve various modulatory
      functions of the synaptic transmission in the primate striatopallidal complex.
      Furthermore, their pattern of localisation raises issues about their roles and
      mechanisms of activation in normal and pathological conditions. Because of their
      'modulatory' functions, these receptors are ideal targets for chronic drug
      therapies in neurodegenerative diseases such as Parkinson's disease.

PMID- 10923991
TI  - Late-onset neurodegenerative diseases--the role of protein insolubility.
AB  - Recently, mutations of the alpha-synuclein gene were found to cause dominantly
      inherited Lewy-body Parkinson's disease (PD) and alpha-synuclein was identified
      as a major component of the Lewy body. However, the cause of the common form of
      PD, with a multifactorial rather than autosomal dominant inheritance pattern,
      remains unknown. Alpha-synuclein precipitates slowly and apparently spontaneously
      at high concentration in solution and the mutations that cause PD accelerate
      precipitation. Other dominantly inherited late-onset or adult-onset dominantly
      inherited neurodegenerative diseases are associated with precipitation of
      proteins. In Alzheimer disease, beta-amyloid and tau abnormalities are present
      and in prion disorders, prion proteins are found. In Huntington disease, a
      disorder with expanded CAG repeats, huntingtin precipitates occur. In dominantly
      inherited spinocerebellar ataxias, also expanded CAG repeat disorders, the
      corresponding ataxin protein precipitates are found. In multiple system atrophy,
      alpha-synuclein precipitates are encountered and in progressive supranuclear
      palsy, tau precipitates occur. In familial amyotrophic lateral sclerosis, a group
      of dominantly inherited disorders, SOD1 precipitates are found. Most of these
      disorders can involve the basal ganglia in some way. Since similar processes seem
      to affect neurons of adults or older individuals and since a relatively limited
      group of proteins seems to be involved, each producing a form of
      neurodegeneration, it is possible that certain common features are present that
      affect this group of proteins. Candidates include a conformational shift, as in
      prions, an abnormality of the ubiquitin-proteosome pathway, as seen in PD, an
      abnormality of a pathway preventing precipitation (e.g. chaperonins), or
      potentiation of a pathway promoting precipitation (e.g. gamma-glutamyl
      transpeptidase) or apoptosis. Elucidation of the pathways causing this protein
      insolubilisation is the first step towards approaching prevention and reversal in
      these late-onset neurodegenerative diseases.

PMID- 10923992
TI  - Of mice and men: solving the molecular mysteries of Huntington's disease.
AB  - Recent advances in the manipulation of mouse embryos provide opportunities for
      the disciplines of neuroscience and molecular genetics to join forces and tackle
      some previously intractable questions in this area of research. Even Huntington's
      disease has started to yield clues to its complex pathophysiology as a result of
      the recent application of transgenic technologies. This short review, while
      necessarily providing some background clinical information on Huntington's
      disease, will focus on how modifications of the mouse genome have contributed,
      and are continuing to contribute, to our understanding of the complex disease
      process. Such new insights may well turn the hope of developing the first
      effective treatment for this devastating disease into reality.

PMID- 10923993
TI  - The AS/AGU rat: a spontaneous model of disruption and degeneration in the
      nigrostriatal dopaminergic system.
AB  - The AS/AGU rat provides an alternative to experimentally produced laboratory
      models of basal ganglia disorders. This mutant is characterised by disturbances
      of movement including clumsy gait, whole body tremor, rigidity and difficulty in
      initiating movement. From an early age, there is a profound depletion of
      extracellular dopamine in the dorsal caudate-putamen as measured via in vivo
      microdialysis; levels are only 10-20% of those found in the parent Albino Swiss
      (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and,
      later still, loss of dopaminergic cells in the substantia nigra pars compacta.
      The dysfunction in movement and the nigrostriatal dopaminergic system are clearly
      linked, since movement can be ameliorated by L-DOPA administration. Furthermore,
      there are depletions in glucose utilisation in several regions of the basal
      ganglia circuitry, including the substantia nigra pars compacta, the subthalamic
      nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique
      opportunity to investigate the intrinsic factors controlling the integrity of
      dopaminergic systems and the recent successful positional cloning of the agu gene
      will allow the molecular mechanisms underlying this interesting phenotype to be
      analysed.

PMID- 10923994
TI  - Alcoholism susceptibility loci: confirmation studies in a replicate sample and
      further mapping.
AB  - BACKGROUND: There is substantial evidence for a significant genetic component to
      the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2,
      and 7 in a large data set that consisted of 105 families, each with at least
      three alcoholic members. METHODS: Additional genotyping in the 105 families has
      been completed in the chromosomal regions identified in the initial analyses, and
      a replication sample of 157 alcoholic families ascertained under identical
      criteria has been genotyped. Two hierarchical definitions of alcoholism were
      employed in the linkage analyses: (1) Individuals who met both Feighner and DSM
      III-R criteria for alcohol dependence represented a broad definition of disease;
      and (2) individuals who met ICD-10 criteria for alcoholism were considered
      affected under a more severe definition of disease. RESULTS: Genetic analyses of
      affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the
      replication data set as well as in a combined analysis of the two samples (LOD =
      2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD =
      2.9). The LOD score on chromosome 2 in the initial data set increased after
      genotyping of additional markers; however, combined analyses of the two data sets
      resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding
      of linkage to chromosome 3 was identified in the replication data set (LOD =
      3.4). CONCLUSIONS: Analyses of a second large sample of alcoholic families
      provided further evidence of genetic susceptibility loci on chromosomes 1 and 7.
      Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3
      that may act only in one of the two data sets.

PMID- 10923995
TI  - Contribution of gastric oxidation to ethanol first-pass metabolism in baboons.
AB  - BACKGROUND: A portion of ingested alcohol does not reach the systemic blood,
      undergoing a first-pass metabolism (FPM) during gastric and hepatic circulation.
      METHODS: To determine whether the stomach can metabolize sufficient ethanol to
      account for the FPM, and to what extent gastric alcohol dehydrogenase (ADH)
      activity is responsible, the hepatic vein, the portal vein, and the aorta were
      cannulated nonocclusively in baboons to measure the conversion of ethanol to
      acetate in vivo. 14C-ethanol (300 mg/kg as a 15% solution) was given
      intragastrically (IG) whereas 3H-acetate was continuously infused intravenously
      (IV). 14C-acetate was measured after exhaustive evaporation of ethanol.
      Simultaneous sampling of hepatic venous, portal and arterial blood was carried
      out for 3 hr, at the end of which the same alcohol dose was given IV to calculate
      the Michaelis-Menten parameters of elimination. RESULTS: Analysis of the IV and
      IG ethanol curves revealed a FPM of 94+/-11 mg/kg (31% of dose). The portal
      arterial differences were negative for 3H-acetate (indicating net extraction) and
      positive for 14C-ethanol and 14C-acetate (indicating net output). Portal acetate
      production (extraction plus net output multiplied by the portal plasma flow)
      increased with time and accounted, over the first 3 hr (82+/-13 mg/kg), for 87%
      of the FPM. Alcohol oxidation by gastric ADH activity (28.7+/-7.2 mg/kg)
      accounted for only 31% of the FPM. CONCLUSIONS: The in vivo oxidation of ethanol
      to acetate in the upper digestive tract accounts for the FPM of ethanol and is
      mediated, at least in part, by ADH activity.

PMID- 10923996
TI  - Ethanol uses cAMP-independent signal transduction mechanisms to activate
      proenkephalin promoter activity in rat C6 glioma cells.
AB  - BACKGROUND: Previous in vivo studies show that acute ethanol exposure
      sequentially increases protein kinase A (PKA) activity, the phosphorylation of
      the adenosine 3':5'-cyclic monophosphate (cAMP)-dependent transcription factor,
      CREB, and finally proenkephalin gene expression. The present study was conducted
      to determine if ethanol could activate directly the adenylyl cyclase pathway and
      thus enhance proenkephalin promoter activity. METHODS: Cultured rat C6 glioma
      cells stably transfected with a segment of the five prime flanking region of rat
      proenkephalin promoter (nucleotide -2700+/-53) ligated to the chloramphenicol
      acetyltransferase (CAT) reporter gene were employed to study the effects of
      ethanol on proenkephalin promoter activity. This region of proenkephalin promoter
      contains two cAMP response elements (CRE-1 and CRE-2) and one AP2 site located in
      the region upstream of the TATA box. Cultures were exposed to ethanol,
      isoproterenol, and phorbol-12, myristate 13-acetate (PMA) alone and in
      combination, in the presence and absence of PKA and protein kinase C (PKC)
      inhibitors. RESULTS: Ethanol and isoproterenol increased proenkephalin promoter
      activity in a dose-dependent manner. Ethanol had an additive effect on maximal
      isoproterenol-stimulated proenkephalin promoter activity, which suggested that
      ethanol used a cAMP-independent signal transduction pathway to increase
      proenkephalin promoter activation. In contrast with isoproterenol, ethanol
      exposure did not increase cAMP accumulation, PKA activity, or the phosphorylated
      form of CREB. However, ethanol exposure modestly increased PKC activity. The PKA
      specific inhibitor, Rp-cAMP, dampened isoproterenol-induced activation of CAT
      activity but did not alter ethanol's ability to increase CAT activity. However,
      the PKC inhibitors, chelerthyrine and G07874, abrogated ethanol's effect of CAT
      activity but did not alter isoproterenol's effects. CONCLUSIONS: Ethanol enhanced
      proenkephalin promoter activity and potentiated isoproterenol-stimulated promoter
      activity through a cAMP-independent pathway.

PMID- 10923997
TI  - Disulfiram treatment increases plasma and red blood cell acetaldehyde in
      abstinent alcoholics.
AB  - BACKGROUND: Much of alcohol's toxicity is due to its product, acetaldehyde. The
      role of acetaldehyde derived from endogenous sources was assessed in alcoholic
      patients administered disulfiram, an inhibitor of aldehyde dehydrogenase.
      METHODS: The first part of the study included 23 subjects without biochemical or
      clinical evidence of chronic liver disease who were abstinent for 2 weeks; 11
      patients were started on disulfiram (250 mg/day), whereas the other 12 were not
      given disulfiram and served as controls. The second part of the study included 13
      alcoholic patients with clinical or pathological evidence of cirrhosis who also
      were administered disulfiram for 2 weeks. Plasma and red blood cell (RBC)
      acetaldehyde as well as serum transaminases were measured at baseline and after 1
      and 2 weeks of treatment. RESULTS: In the disulfiram-treated group of alcoholics
      without known cirrhosis, RBC acetaldehyde levels increased from the pretreatment
      value of 2.98+/-0.18 microM to 4.14+/-0.33 microM after 1 week and to 4.14+/-0.26
      microM after 2 weeks of treatment (p < 0.001). Compared with the pretreatment
      values (2.07+/-0.24 microM), plasma acetaldehyde levels also increased after 1
      week (3.18+/-0.32 microM) and 2 weeks (3.15+/-0.26 microM) of disulfiram
      treatment (p < 0.001). There were no significant differences in sequential levels
      measured in either plasma or RBC acetaldehyde levels in patients who were not
      administered disulfiram. In the group of cirrhotic patients, the mean baseline
      RBC acetaldehyde value (3.60+/-0.22 microM) was significantly higher than in
      noncirrhotics. Disulfiram therapy increased the RBC acetaldehyde after 1 week
      (4.63+/-0.27 microM, p < 0.001) and 2 weeks of treatment (4.06+/-0.28 microM, p <
      0.05). Compared with baseline values, plasma acetaldehyde levels were
      significantly higher after 1 week but not after 2 weeks of disulfiram. There were
      no significant differences among serum transaminases in alcoholics administered
      disulfiram, although three cirrhotic patients did have clinically significant
      elevations. CONCLUSIONS: In abstaining subjects given disulfiram, acetaldehyde
      concentrations increase, possibly due to diminished catabolism of endogenously
      generated acetaldehyde. Disulfiram should be given cautiously, especially in
      patients with cirrhosis.

PMID- 10923999
TI  - Serotonergic function, behavioral disinhibition, and negative affect in children
      of alcoholics: the moderating effects of puberty.
AB  - BACKGROUND: Serotonergic (5-HT) dysfunction has been implicated in both
      behavioral disinhibition and negative affect in adults. Although our group's
      previous work found decreased whole blood 5-HT in high versus low behavior
      problem children of alcoholics, some child/adolescent studies report conflicting
      results, and 5-HT's role in negative affect has been largely unexamined. Age
      related developmental factors may play a role in these relationships. METHODS:
      This report is from an ongoing prospective study of the development of risk for
      alcohol abuse/dependence and other problematic outcomes in a sample of families
      subtyped by father's alcoholism classification. The present study extends
      previous work and examines relationships between whole blood 5-HT and both child
      behavioral disinhibition (an aggression index from the Child Behavior Checklist)
      and negative affect (Child Behavior Checklist Anxious/Depressed scale) in
      offspring from 47 families (N = 45 boys and 17 girls; mean age = 10.88+/-2.03
      yr). RESULTS: The most important finding was that puberty moderated relationships
      between 5-HT and both behavioral disinhibition and negative affect with a
      relationship for pubescent children (n = 14, r = -0.54, p = 0.05: r = -0.57,p =
      0.04, respectively) but no relationship for prepubescent children (n = 48, r =
      0.05, p = 0.75; r = -0.15, p = 0.31, respectively). CONCLUSIONS: The moderating
      effects of puberty may help clarify inconsistencies in child/adolescent
      literature. Furthermore, there appears to be a relationship between 5-HT and
      negative affect which parallels that between 5-HT and behavioral disinhibition.
      Pubertal status may be an important variable to evaluate as a moderator in
      relation to the developmental context of the role 5-HT dysfunction may play in
      various models of behavior related to alcoholism over the early life course.

PMID- 10923998
TI  - Basis of variable sensitivities of GABA(A) receptors to ethanol.
AB  - BACKGROUND: The GABA(A) system is believed to be one of the crucial target sites
      for ethanol. However, in the literature, data using various preparations yielded
      controversial conclusions regarding the ethanol potency to modulate the activity
      of GABA(A) receptors. We have previously shown that the potency of n-alcohols to
      potentiate GABA-induced currents is correlated with their carbon chain length.
      This correlation was further compared among four cell types in an attempt to
      explain the variable potencies of ethanol to potentiate GABA responses. METHODS:
      Whole-cell patch clamp experiments were performed to determine and compare the
      potencies of n-alcohols in potentiating GABA-induced currents in rat dorsal root
      ganglion (DRG) neurons, human embryonic kidney cells expressing the rat
      alpha1beta2gamma2S or alpha1beta2gamma2L subunits, and rat cortical neurons.
      RESULTS: The GABA(A) receptors of the four cell types tested were all sensitive
      to n-alcohols, albeit with different potencies and efficacies. The effective
      concentration to increase GABA-induced currents to 125% of control (EC125) was
      correlated with the carbon chain length of n-alcohols, but slopes for this
      relationship are different among DRG neurons, the alpha1beta2gamma2S, and
      alpha1beta2gamma2L subunits. Thus, the potencies of lower alcohols such as
      ethanol differed among these cell types although higher alcohols such as n
      octanol were almost equally potent. In cortical neurons, however, the
      relationship was shifted in the direction of longer carbon chains, indicating
      that their sensitivity was lower than those of the other three cell types. The
      ethanol EC125 values as obtained by experiments or those by extrapolation (in
      parenthesis) from the EC125-carbon chain length relationship were: 169 (103) mM
      for DRG neurons, 501 (333) mM for the alpha1beta2gamma2L subunits, 781 (674) mM
      for the alpha1beta2gamma2S subunits, and (1897) mM for cortical neurons.
      CONCLUSIONS: It was concluded that the GABA(A) receptors of these four cell types
      were basically sensitive to n-alcohols including ethanol but the sensitivity
      curve was shifted to the lower side in the order of decreasing sensitivity of DRG
      neurons > alpha1beta2gamma2L > alpha1/beta2gamma2S > cortical neurons.

PMID- 10924000
TI  - A behavioral economic analysis of concurrent ethanol- and water-reinforced
      responding in different preference conditions.
AB  - BACKGROUND: The reinforcing properties of orally self-administered drugs have
      been evaluated by using choice procedures. The preference for the drug over a
      nondrug alternative has indicated that the drug has greater value than the
      nondrug alternative as a reinforcer at some drug concentrations. However, at
      large drug concentrations, the fluid deliveries of the drug may be equal to or
      less than those of the nondrug alternative, whereas the actual drug intake
      (milligrams per kilogram of body weight) may continue to increase. In this study,
      we used behavioral economics to evaluate the reinforcing strength of ethanol in
      conditions where baseline ethanol fluid deliveries were greater than, equal to,
      or less than those of the concurrently available water. METHODS: Four male rhesus
      monkeys were allowed access to ethanol (2%, 8%, or 32%) and water for 2 hr/day
      under a fixed ratio (FR) 4 reinforcement schedule. At each ethanol concentration,
      the FR for both fluids was gradually increased to FR 64. RESULTS: During the FR 4
      schedule, the fluid deliveries of ethanol at 2%, 8%, and 32% were greater than,
      equal to, and less than those of water, respectively. When the FR was increased
      at 2% ethanol, fluid deliveries and responding decreased for both the ethanol and
      water. When the FR was increased at 8% ethanol, water fluid deliveries and
      responding decreased more rapidly than did those of ethanol. When the FR was
      increased at 32% ethanol, the ethanol fluid deliveries remained the same across
      all FRs, whereas water fluid deliveries decreased rapidly. At 8% and 32% ethanol,
      the responding for ethanol, relative to water, increased dramatically.
      CONCLUSIONS: In behavioral economic terms, demand for ethanol was more inelastic
      regardless of whether the ethanol or water maintained more absolute fluid
      deliveries at baseline FRs. Therefore, researchers should examine the reinforcing
      effects of ethanol in a variety of concentration and schedule conditions rather
      than drawing inferences regarding reinforcing effects simply based on a
      preference measure.

PMID- 10924001
TI  - Cigarette smoking decreases the prolactin response to serotonergic stimulation in
      subgroups of alcoholics and controls.
AB  - BACKGROUND: The prolactin response to serotonergic stimulation has been used as
      an index of central nervous system serotonin function. We evaluated the prolactin
      response to d,l-fenfluramine to determine whether subtypes of alcoholics differed
      in prolactin responsivity compared with nonalcoholics and whether cigarette
      smoking affected prolactin response. METHODS: One hundred ten healthy, abstinent
      men across four groups (controls [23% smokers]; alcoholics [72% smokers];
      alcoholics with antisocial personality disorder [94% smokers]; nonalcoholic
      antisocials [88% smokers]) received d,l-fenfluramine (100 mg orally) in a
      randomized, double-blind, placebo-controlled study. Plasma prolactin levels were
      obtained at baseline and at half-hour intervals for 5 hr after
      fenfluramine/placebo administration. Plasma fenfluramine and norfenfluramine
      levels were obtained hourly. RESULTS: Smokers had a blunted prolactin response to
      fenfluramine compared with nonsmokers without any alcoholism or antisocial
      personality effects. Using a cutoff point of delta peak prolactin < 10 ng/ml,
      more smokers (41/76, 54%) had a dampened response to fenfluramine than did
      nonsmokers (7/34, 21%) [chi2(1) = 10.6, p < 0.003]. The percentage of low
      responders was greatest among smokers regardless of whether they were healthy
      controls, alcoholics, or antisocial. Multiple regression revealed that three
      variables--(1) number of pack-years of smoking, (2) actual dosage of fenfluramine
      received, and (3) plasma norfenfluramine level obtained--explained 43% of the
      variance (R2 = 0.43) in delta prolactin area under the curve. Variables that
      included alcoholism diagnostic status, antisocial personality diagnostic status,
      and impulsive aggressive personality, depressive, and suicidal traits failed to
      explain any additional unique variance. CONCLUSIONS: Cigarette smoking blunted
      the prolactin response to a pharmacological challenge with d,l-fenfluramine.
      Pharmacodynamic and pharmacokinetic factors related to smoking both appear to
      influence fenfluramine-induced prolactin secretion. Phenotypes of alcoholics did
      not differ in their prolactin response to this serotonergic probe.

PMID- 10924002
TI  - Acute effects of ethanol and the first suckling episode in the newborn rat.
AB  - BACKGROUND: In humans, early postnatal experience with alcohol is far from rare
      and includes exposure to alcohol through breast milk or through the bottle to
      attain sedative effects (Croce, 1987). Exposure to alcohol though mother's milk
      alters the infant's suckling behavior. However, acute effects of alcohol on
      suckling behavior using animal models remain to be investigated. METHODS: The
      present study was designed to examine the effects of neonatal alcohol exposure on
      attachment to a surrogate nipple and ingestion of milk in rat pups, naive both to
      suckling and to maternal care. Cesarean-delivered rat pups were pre-exposed to
      four dosages of ethanol (0, 1, 2, and 3 g/kg intragastrically) and tested 30 min
      after ethanol administration. RESULTS: Suckling behavior was impaired only in
      pups exposed to a dosage of 3 g/kg of ethanol. Pups in this group demonstrated
      longer latency to attach followed by less efficient suckling--the pups maintained
      contact with the nipple but showed decreased ingestion of milk from it. Pups
      treated with 1 g/kg of ethanol showed the greatest suckling efficiency, ingesting
      far more milk per minute attached to the surrogate nipple than pups in all other
      groups. At the same time, nonevoked motor activity was significantly suppressed
      by all three dosages of ethanol. Blood alcohol levels showed a linear
      relationship with dose at 30 min postintubation. CONCLUSIONS: These findings
      suggest a dissociation between acute ethanol effects on suckling and overall
      motor activity, with suckling apparently less sensitive to suppressive and more
      sensitive to activating effects of ethanol.

PMID- 10924003
TI  - Alcohol and the continuation of early marital aggression.
AB  - BACKGROUND: Husband alcohol use has frequently been found to be related to
      husband-to-wife marital violence. Research has demonstrated a prospective link
      between husband alcohol use before marriage and husband-to-wife aggression in the
      first year of marriage. The present study examined the relationships of husband
      violence, marital conflict, and couple's alcohol use in the first year of
      marriage to husband-to-wife marital violence in the second and third years of
      marriage. METHODS: Newlywed couples were recruited at the time of marriage and
      were interviewed regarding alcohol use and experience with violence before
      marriage, 1 year after marriage, and 3 years after marriage. RESULTS: Year 1
      violence was predictive of subsequent marital violence. Husband and wife drinking
      patterns in the first year of marriage interacted to predict violence in later
      years. The most violence in subsequent years occurred in couples where the
      husband was a heavy drinker and the wife was not. Husbands who were violent in
      year 1 were more likely to be violent in later years. When no violence occurred
      in the first year, frequent use of verbal aggression in year 1 was predictive of
      violence in subsequent years. CONCLUSIONS: The predictive value of husband
      drinking patterns for subsequent violence extends beyond the transition to
      marriage. The fact that husband and wife alcohol use interacted to predict future
      aggression suggests that the relationship between husband alcohol use and marital
      violence is not spurious nor the result of conflict and violence promoting
      alcohol use. The findings may reflect multiple instances of acute intoxication
      and/or alcohol-related stress and conflict within the relationship, both of which
      may increase the likelihood of aggression.

PMID- 10924004
TI  - Occupational stress factors and alcohol-related behavior in urban transit
      operators.
AB  - BACKGROUND: If alcohol consumption mitigates psychological and physiological
      aspects of the response to stressors, then alcohol consumption might be elevated
      for individuals exposed to high occupational stressors. Frequency of work
      stressors and reaction to those stressors were studied in relation to several
      alcohol-related outcomes. METHODS: During the period 1993-1995, 1979 transit
      operators underwent medical examinations for commercial driver's license renewal.
      Questionnaire and interview data concerning occupational stress factors and
      alcohol-related outcomes were available for 1386 (70.2%) of the operators.
      RESULTS: A positive association was found between the two job stressor-related
      measures and each of six alcohol-related outcomes. Of these 12 associations, ten
      were statistically significant. Individuals experiencing high self-reported
      frequency of job stressors and a higher perceived severity of those job stressors
      were more likely to drink and more likely to be heavy drinkers. They reported
      more consequences of alcohol consumption, reported increased consumption since
      beginning work as transit drivers, and were more likely to report drinking to
      deal with work stress. They also drank more, but this effect was not significant
      for either job stress measure. There was virtually no association between either
      stressor-related measure and alcohol dependency (CAGE). CONCLUSIONS: Together
      with other published findings, these results suggest increased alcohol-related
      outcomes in the presence of work stressors. This conclusion has potential
      implications for worksite health promotion and job design. Because our findings
      are cross-sectional, further research is needed to clarify the causal nature of
      the work stressor-alcohol association. Further research also is needed to clarify
      the role of individual differences and context.

PMID- 10924005
TI  - Intellectual, cognitive, and academic performance among sons of alcoholics,
      during the early school years: differences related to subtypes of familial
      alcoholism.
AB  - BACKGROUND: Research on intellectual and cognitive functioning of children of
      alcoholics has been marked by inconsistency, with some studies unable to document
      deficits. This discrepancy may reflect the substantial heterogeneity found in the
      alcoholic population and among families of alcoholics. The current study sought
      to examine the effects of familial alcoholism subtypes on intellectual,
      cognitive, and academic performance in early school-aged sons of alcoholics.
      METHODS: Subjects for the present study were 198 elementary-age boys who were
      participants in the larger MSU-UM Longitudinal Study. Familial alcoholism
      subtypes were determined based on fathers' alcoholism and antisocial personality
      disorder diagnoses. Intellectual functioning was measured with the Wechsler
      Intelligence Scale for Children-Revised (WISC-R); academic achievement was
      measured with the Wide Range Achievement Test-Revised. In addition, Mazes and
      Freedom from Distractability factor scores of the WISC-R were used to assess
      abstract planning and attention abilities. RESULTS: Children of antisocial
      alcoholics (AALs) displayed the worst IQ and academic achievement compared with
      children of nonantisocial alcoholics (NAALs) and controls. In addition, children
      of AALs displayed relatively poorer abstract planning and attention abilities
      compared with children from control families. Regression analyses revealed that
      familial alcoholism subtype continued to account for variance in child
      intellectual ability even when other factors were excluded. CONCLUSIONS: Findings
      indicate that children from AAL families are most susceptible to relative
      intellectual, cognitive, and academic deficits. The study further supports the
      proposition that familial risk characteristics (i.e., paternal alcoholism and
      antisociality) may serve as effective indicators of family risk for poor
      intellectual outcome among offspring as early as the elementary school years.

PMID- 10924006
TI  - The influence of traits of disinhibition on the association between alcohol use
      and risky sexual behavior.
AB  - BACKGROUND: Past research has demonstrated a link between alcohol use and risky
      sexual behavior; the processes that may underlie this association remain largely
      unexplored, however. Recent studies suggest that personality traits such as
      excitement seeking, impulsivity, and social deviance proneness may play an
      important role in both behaviors. METHODS: A structural model of the association
      between disinhibited personality traits, alcohol use, and risky sexual behavior
      (sex with strangers/one-night stands) was tested. We recruited a sample of 410
      college students that reported a wide range of scores on self-reported measures
      of disinhibition. We hypothesized that disinhibited personality characteristics
      would be primarily responsible for the association between risky sexual behavior
      and alcohol problems. A third-variable model was proposed to demonstrate this
      association. RESULTS: The results suggested that the relationship between alcohol
      use and risky sexual behavior is best explained by their common association with
      excitement seeking. There was a significant correlation between alcohol use and
      risky sexual behavior when considered alone. However, when controlling for the
      effects of personality, the correlation was nonsignificant. In a final model,
      both excitement seeking and social deviance proneness were found to be
      significantly associated with alcohol use, and excitement seeking was
      significantly related to risky sexual behavior. CONCLUSIONS: Results suggest the
      relationship between alcohol use and risky sexual behavior is best characterized
      by a common association with excitement seeking.

PMID- 10924007
TI  - Decision-making biases, antisocial personality, and early-onset alcoholism.
AB  - BACKGROUND: Disinhibited, antisocial traits increase the risk for early-onset
      alcoholism. Research also suggests that decision biases which favor immediate
      large rewards regardless of long-term consequences may be important mechanisms
      associated with the biological substrates of antisocial traits. This study tested
      the hypothesis that early-onset alcoholism with antisocial personality (ASP)
      would be associated with favoring immediate larger rewards despite their being
      associated with long-term losses. METHODS: Twenty-seven early-onset alcoholics
      with and without a diagnosis of ASP, eight subjects with ASP but no alcohol
      dependence, and 32 controls were tested on a task that manipulated the magnitude
      of immediate rewards and the magnitude of long-term punishments. The sample was
      recruited from the community via advertisements. RESULTS: Compared with subjects
      without ASP, subjects with ASP favored larger immediate rewards despite long-term
      losses regardless of alcohol dependence; however, they learned to shift their
      decisions in a more advantageous direction over time. A disadvantageous decision
      bias also was associated with drinking greater quantities of alcohol and having a
      lower IQ. CONCLUSIONS: This study suggests that ASP in a young adult
      noninstitutionalized sample was associated with a pattern of disadvantageous
      decision making similar to that observed in patients with antisocial behavioral
      characteristics associated with lesions in the ventromedial frontal cortex. The
      data also suggest that this pattern of disadvantageous decision making is
      associated with consuming larger quantities of alcohol but not consuming alcohol
      more frequently.

PMID- 10924008
TI  - Sertraline treatment for alcohol dependence: interactive effects of medication
      and alcoholic subtype.
AB  - BACKGROUND: Characteristic behaviors of some alcohol-dependent individuals, e.g.,
      binge drinking, comorbid psychopathology, and some types of alcohol-related
      problems, have been linked to abnormalities in serotonergic neurotransmission.
      However, studies that have evaluated serotonergic pharmacotherapy for reducing
      drinking have yielded conflicting results. One explanation for these findings is
      a general failure to distinguish alcohol subgroups that may be differentiated on
      the basis of serotonergic abnormalities. However, in 1996, Kranzler and
      colleagues reported that Type B alcoholics, who are characterized by high levels
      of premorbid vulnerability, alcohol dependence severity, and comorbid
      psychopathology, showed less favorable drinking outcomes in response to treatment
      with fluoxetine, a serotonin reuptake inhibitor, than with placebo. This
      medication effect was not seen in Type A alcoholics, i.e., those with lower
      risk/severity of alcoholism and psychopathology. The aim of the present study was
      to explore the validity of differential responding by alcohol-dependent subtypes
      using the serotonin reuptake inhibitor, sertraline. METHODS: A k-means clustering
      procedure was applied to a sample of alcohol-dependent subjects enrolled in a 14
      week, placebo-controlled trial of 200 mg/day of sertraline, classifying them into
      lower-risk/severity (Type A: n = 55) and higher-risk/severity (Type B: n = 45)
      subgroups. RESULTS: A significant interaction between alcoholic subtype and
      medication condition was found, confirming the findings of Kranzler and
      colleagues that alcoholic subtypes responded differentially to serotonergic
      medication. Somewhat at variance with their results, however, the present study
      showed that the lower risk/severity (Type A) subjects had more favorable outcomes
      when treated with sertraline compared to placebo. CONCLUSIONS: Alcoholic subtypes
      differentially responded to sertraline when used as a treatment to reduce alcohol
      drinking, with one subtype having more favorable outcomes. Subtyping alcoholics
      may help to resolve conflicting findings in the literature on serotonergic
      treatment of alcohol dependence.

PMID- 10924009
TI  - Role of alcohol in unnatural deaths: a study of all deaths in Sweden.
AB  - BACKGROUND: Most previous research has concentrated on the role of alcohol in one
      type of unnatural death in a selected population, but the present objective was
      to investigate the role of alcohol in all unnatural deaths (autopsied and not
      autopsied). METHODS: All cases of unnatural death from 1992 through 1996 in
      Sweden were analyzed (n = 23,132). Death was attributed at least in part to
      alcohol if the deceased was a "known alcoholic"; if the underlying or
      contributing cause of death was alcohol-related; if the deceased had an alcohol
      related inpatient diagnosis during the 3-year period prior to death; or if the
      deceased tested positive for blood alcohol. RESULTS: Just over 28% of the
      unnatural deaths could be associated with alcohol; the association with alcohol
      was more than twice as common in deaths of males (35%) as in females (16%). When
      only autopsied cases or only blood-tested cases were taken as the denominators,
      38% and 44%, respectively, of the deaths were associated with alcohol. Alcohol
      involvement also was twice as common in intentional deaths (36%) as in
      unintentional deaths (18%). The intoxication group (78%) had the highest fraction
      of deaths that could be associated with alcohol, followed by the undetermined
      group (62%), homicide (49%), fire (41%), suicide (35%), asphyxia (29%), traffic
      (18%) and fall (9%) groups. In the 20- to 59-year age group, alcohol involvement
      was found in 51% of the males and 35% of the females (47% for males and females
      combined). CONCLUSIONS: The present estimates are conservative; alcohol
      involvement in unnatural deaths probably is even higher, up to 44% of the total.
      The present estimation is an important step in policy-making to lower the number
      of alcohol-related deaths in Sweden.

PMID- 10924010
TI  - Hospital morbidity of alcohol use disorders in the center of France.
AB  - BACKGROUND: The Auvergne region of central France has the third highest mortality
      rate in the country for alcohol-related disorders and the highest level of
      alcohol consumption among young people. METHODS: An exhaustive cross-sectional
      study of regional hospital morbidity related to alcohol was undertaken on a
      single day in May 1998, including 9,552 hospital beds. All inpatients age 16 and
      older in the Departments of Medicine, Surgery, Obstetrics and Gynecology,
      Psychiatry, and Medium-Stay Services were studied. The aim was to define alcohol
      related behavior patterns (by using the Diagnostic and Statistical Manual of
      Mental Disorders [DSM-IV] criteria of abuse and dependence and the CAGE
      questionnaire) and to measure the proportion of nonsomatic alcohol-related care
      dispensed in hospital. RESULTS AND CONCLUSIONS: The prevalence of alcohol use
      disorders in all wards was 20%. Half of these patients were alcohol dependent, a
      quarter were diagnosed as alcohol abusers, and a quarter had an alcohol-related
      problem that was not identified during the stay. Alcohol use disorders were more
      common in male inpatients (34% vs. 8% in female inpatients) and in certain age
      groups. One male subject in two and one female subject in five between 34 and 45
      years had an alcohol-related problem. Almost 25% of male inpatients studied
      between the ages of 16 and 20 years had an alcohol-related problem, but only half
      had been diagnosed previously. Hospital care for alcohol-related health problems
      was seriously inadequate. On average, 38% of patients diagnosed with an alcohol
      use disorder received relevant nonsomatic alcohol care, of which 13% were alcohol
      abusers and 50% were alcohol-dependent patients. SIGNIFICANCE: This exhaustive
      study demonstrates the degree of alcohol-related morbidity among hospitalized
      patients, which is particularly high in men, in the Auvergne region of France.
      The study emphasizes the lack of diagnosis, particularly for the young, and the
      apparent deficiencies in the hospital management of these patients.

PMID- 10924011
TI  - Ethanol inhibition: the humoral and cellular immune response to hepatitis C virus
      NS5 protein after genetic immunization.
AB  - BACKGROUND: The combination of chronic hepatitis C virus (HCV) and ethanol may
      increase viral replication, impair cellular immunity, and result in severe and
      progressive liver disease. Because HCV nonstructural proteins play a major role
      in viral elimination, we examined the cellular and humoral immune responses after
      genetic immunization against NS5 in a chronic ethanol mouse model. METHODS: Mice
      were fed an ethanol or isocaloric pair-fed control liquid diet and were immunized
      with HCV NS5-expression plasmid. RESULTS: The humoral and cellular arms of the
      immune system were significantly impaired in ethanol-fed mice. Abstinence
      partially reversed the inhibitory effects on antibody levels and the CD4+
      proliferative immune response but did not restore the CD8+ cytotoxic T-cell
      response to this HCV nonstructural protein. Furthermore, we determined whether
      murine interleukin-2 coadministration with the NS5 expression plasmid would
      reverse the inhibitory effects of chronic ethanol consumption; again, partial
      restoration was observed for B-cell and CD4+ T-cell activity, but not for
      cytotoxic T cells. CONCLUSIONS: These results suggest that the high rate of
      chronic HCV infection in alcoholics may be due to ethanol's effects on antiviral
      immune responses.

PMID- 10924012
TI  - Mitochondrial glutathione replacement restores surfactant synthesis and secretion
      in alveolar epithelial cells of ethanol-fed rats.
AB  - BACKGROUND: Chronic alcohol abuse increases the incidence and severity of acute
      lung injury in critically ill patients. Previously we determined that ethanol
      ingestion in rats dramatically decreased alveolar epithelial cellular levels of
      glutathione and surfactant synthesis and secretion in vitro. Previous studies in
      alcoholic liver disease suggest that mitochondrial glutathione levels, and not
      cellular levels per se, are involved in the pathogenesis of ethanol-mediated
      hepatotoxicity. Therefore, we hypothesized that alveolar epithelial mitochondrial
      glutathione depletion mediates the observed defects in surfactant synthesis and
      secretion in ethanol-fed rats. METHODS: Male Sprague-Dawley rats were fed the
      Lieber-DeCarli liquid diet with or without ethanol (36% of total calories) for 6
      weeks. In some experiments, ethanol-fed rats were then switched to the control
      diet for 1 week, with or without glutathione supplementation with either N
      acetylcysteine (NAC) or procysteine (PRO). Alveolar epithelial type II cells were
      then isolated and glutathione levels (cytosolic and mitochondrial) and surfactant
      production (synthesis and secretion) were determined. RESULTS: Ethanol ingestion
      decreased (p < 0.05) mitochondrial and cytosolic levels of glutathione, and
      surfactant synthesis and secretion in isolated type II cells when compared to
      cells from control-fed rats. NAC treatment restored (p < 0.05) cytosolic but not
      mitochondrial glutathione levels (p > 0.05), and had no effect (p > 0.05) on
      surfactant synthesis and secretion in type II cells isolated from ethanol-fed
      rats. In contrast, PRO treatment restored (p < 0.05) cytosolic and mitochondrial
      glutathione levels, and normalized (p < 0.05) surfactant synthesis and secretion
      in type II cells isolated from ethanol-fed rats. CONCLUSIONS: These results
      suggest that mitochondrial, and not simply cytosolic, replacement of glutathione
      is necessary to improve surfactant function in critically ill patients with a
      history of alcohol abuse.

PMID- 10924013
TI  - Tolerance to acute ethanol inhibition of peptide hormone release in the isolated
      neurohypophysis.
AB  - BACKGROUND: Acute ethanol (EtOH) exposure reduces the evoked release of
      vasopressin (AVP) and oxytocin (OT) from excised neurohypophyses and from
      dissociated neurohypophysial terminals of the rat. METHODS AND RESULTS: Rats
      placed on a diet that maintained blood levels of 30 mM EtOH for 20 to 40 days
      developed tolerance to acute EtOH inhibition of release. In the presence of 10 mM
      EtOH, high (50 mM) K+-induced release of AVP from isolated neurohypophysial
      terminals of EtOH-naive rats was reduced by 77.7+/-1.4%, whereas in the chronic
      EtOH group, release was reduced by only 9.4+/-8.7%. Similar tolerance was evident
      during acute challenge with 75 mM EtOH, as well as for release of OT from
      isolated terminals. Animals treated with an intraperitoneal injection of EtOH and
      sacrificed 90 min postinjection did not exhibit the reduced EtOH inhibition of
      release from dissociated terminals during a 75 mM EtOH acute challenge.
      CONCLUSIONS: The altered component responsible for the tolerance to inhibition of
      release resides in the isolated terminal, because tolerance measured in vitro
      from intact neurohypophyses was similar to that seen in isolated terminals. The
      failure of EtOH-injected animals to exhibit reduced inhibition of release in
      response to an acute EtOH challenge indicates that short-term elevated blood
      alcohol level does not induce this tolerance. The finding of tolerance to EtOH
      induced inhibition of release from the intact neurohypophysis and isolated
      terminals provides a physiological preparation in which to examine the molecular
      targets of acute drug action modified after chronic exposure to the drug.

PMID- 10924014
TI  - Prenatal alcohol exposure and depressive features in children.
AB  - BACKGROUND: This study examined the association between prenatal alcohol exposure
      and self-report of depressive symptoms in 5- to 6-year-old children. Higher
      levels of prenatal alcohol exposure were hypothesized to be associated with
      endorsement of a greater number of depressive symptoms in children. It was also
      hypothesized that maternal depression, although associated with drinking
      behavior, would contribute independently to outcome. Finally, the mother's
      behavior toward the child, as well as current drinking practices, were postulated
      to mediate the relationship between prenatal alcohol exposure and child
      depressive symptoms. METHODS: Participants were 41 mother-child dyads who had
      been followed longitudinally since the children were 1 year of age. Self-report
      questionnaires for maternal and child depression were used. RESULTS: Results
      revealed that prenatal alcohol exposure, maternal depression, and child gender
      seemed to be highly associated with child depressive symptoms. Girls who had
      higher levels of prenatal alcohol exposure and whose mothers acknowledged higher
      levels of depression endorsed the highest number of depressive symptoms. Neither
      the mother's behavior in interaction with the child nor her current level of
      alcohol consumption mediated the relationship. CONCLUSIONS: The importance of
      considering prenatal alcohol exposure as a risk variable in the prediction of
      childhood-onset depression and the possible neurological mechanisms underlying
      depression in children with alcohol exposure in utero are discussed.

PMID- 10924015
TI  - 5-HT transporter sites and 5-HT1A and 5-HT3 receptors in Fawn-Hooded rats: a
      quantitative autoradiography study.
AB  - BACKGROUND: The neuroanatomical profiles of 5-HT1A receptors, 5-HT3 receptors,
      and 5-HT transporters (5-HTT) in the brain of the Fawn-Hooded (FH) rat,
      particularly mesocorticolimbic regions, are not fully elucidated. METHODS: By
      means of in vitro quantitative autoradiography, we used [3H]citalopram, [3H]8-OH
      DPAT, and [3H]GR65630 to label 5-HTT, 5-HT1A receptors, and 5-HT3 receptors in
      the brain of alcohol-naive FH rats, Wistar-Kyoto (WKY) rats, and FH rats given
      free access to 5% ethanol and/or after 24 to 48 hr withdrawal. RESULTS AND
      CONCLUSIONS: In alcohol-naive rats, FH rats displayed significantly higher (p <
      0.05) densities of [3H]citalopram binding in the nucleus accumbens (+30%),
      lateral septum (+37%), ventral pallidum (+21%), and ventral tegmental area
      (+24%), as well as an increased binding of [3H]8-OH-DPAT to 5-HT1A receptors in
      the frontal and parietal cortex (+33%), occipital and temporal cortex (+25%), and
      hippocampal CA3 region (+31%), compared with WKY rats, whereas both strains
      exhibited comparable [3H]GR65630 binding to 5-HT3 receptors. Compared with
      control FH (naive) rats, chronic ethanol consumption significantly decreased (p <
      0.(15)[3H]8-OH-DPAT binding in the frontal and parietal cortex (-15%) but
      significantly increased binding (p < 0.05) in the entorhinal cortex (+25%),
      retrosplenial granular cortex (+20%), and hippocampal CA1 (+14%) and CA3 regions
      (+18%). Moreover, ethanol withdrawal induced the same extent of increased [3H]8
      OH-DPAT binding in the entorhinal and retrosplenial cortex as seen in FH
      (chronic) rats. In contrast, [3H]8-OH-DPAT binding in the hippocampal CA1 and CA3
      regions was decreased by -9% and -20% from the level of chronic ethanol-treated
      FH rat (p < 0.05) and returned to the control level seen in FH (naive) rats.
      SIGNIFICANCE: The elevated 5-HT transporters and 5-HT1A receptors in the
      mesocorticolimbic areas in FH rats may reflect a potential innate altered
      transmission at serotonergic synapses, which possibly may affect the high intake
      of alcohol in FH rats. The region-specific alterations of 5-HT1A receptors in FH
      rat brain after ethanol challenges suggest that 5-HT1A receptors are sensitive to
      ethanol challenges, whereas 5-HTT are apparently insensitive.

PMID- 10924016
TI  - Autoimmune responses against oxidant stress and acetaldehyde-derived epitopes in
      human alcohol consumers.
AB  - BACKGROUND: Studies in experimental animals have indicated that chronic ethanol
      ingestion triggers the formation of antibodies directed against proteins modified
      with reactive metabolites of ethanol and products of lipid peroxidation. However,
      the nature and prevalence of such antibodies have not been compared previously in
      alcoholic patients. METHODS: Autoantibodies against adducts with acetaldehyde-
      (AA), malondialdehyde- (MDA), and oxidized epitopes (Ox) were examined from sera
      of 54 alcohol consumers with (n = 28) or without (n = 26) liver disease, and from
      20 nondrinking controls. RESULTS: Anti-AA-adduct IgA and IgG antibodies were
      elevated in 64% and 31% of patients with biopsy-proven alcoholic liver disease
      (ALD, n = 28), respectively. The IgA titers were significantly higher than those
      from nondrinking controls (p < 0.001), or heavy drinkers without significant
      liver disease (p < 0.001). Anti-MDA adduct titers (IgG) were elevated in 70% of
      the ALD patients. These titers were significantly higher (p < 0.001) than those
      from nondrinking controls, or heavy drinkers without liver disease. Antibodies
      (IgG) against Ox epitopes occurred in 43% of ALD patients, and the titers also
      were significantly higher (p < 0.05) than those from nondrinking controls. The
      anti-AA and anti-MDA adduct titers in ALD patients correlated significantly with
      the combined clinical and laboratory index (CCLI) of liver disease severity (r(s)
      = 0.449, p < 0.05; r(s) = 0.566, p < 0.01, respectively), the highest prevalences
      of anti-AA-adducts (73%) and anti-MDA-adducts (76%) occurring in ALD patients
      with cirrhosis. CONCLUSIONS: The present results indicated that autoantibodies
      against several distinct types of protein modifications are generated in ALD
      patients showing an association with the severity of liver disease.

PMID- 10924017
TI  - Effects of fetal ethanol exposure on pituitary-adrenal sensitivity to
      secretagogues.
AB  - BACKGROUND: Rodents prenatally exposed to ethanol demonstrate hormonal hyper
      responsiveness to stressors in adulthood. The present study examined the
      hypothesis that an increased sensitivity of the adrenal to ACTH and/or the
      pituitary to corticotropin releasing hormone (CRH) after dexamethasone
      suppression, may play a role in the hormonal hyper-responsiveness seen in fetal
      ethanol-exposed rats. METHODS: Sprague-Dawley males and females from prenatal
      ethanol-exposed (E), pair-fed (PF), and ad libitum-fed control (C) groups were
      tested in adulthood (90-120 days). Testing was done in a series of two
      experiments carried out during the trough of the corticosterone rhythm, the time
      of greatest sensitivity to feedback inhibition. Twenty-four to 48 hr before
      testing, jugular cannulae were implanted for hormone infusion and blood sample
      collection. In both experiments, animals were injected intraperitoneally with
      dexamethasone-21-phosphate (DEX) (15 microg/100 g body weight for males or 30
      microg/100 g body weight for females) 3 hr before testing to suppress endogenous
      hypothalamic-pituitary-adrenal (HPA) activity. Animals were given a bolus
      infusion of ACTH (0-0.10 mg/rat) and blood samples (0.2 cc) were drawn at 60-min
      intervals over 240 min for determination of plasma corticosterone (CORT) levels
      (Experiment 1), or were given a bolus infusion of CRH (0-20 microg/kg body wt)
      and samples drawn at 0, 5, 15, and 30 min for determination of plasma ACTH and
      CORT levels (Experiment 2). RESULTS: As expected, sex differences in adrenal
      response to ACTH and pituitary response to CRH were observed; females had higher
      CORT and ACTH levels than males at all concentrations of ACTH and CRH. In
      addition, dose-response relationships between exogenously administered ACTH or
      CRH and plasma CORT were demonstrated; increasing concentrations of secretagogues
      resulted in higher and/or more prolonged CORT responses in both males and
      females. There were no significant differences among E, PF, and C males or
      females in adrenal sensitivity to ACTH. However, prenatal ethanol exposure
      altered pituitary sensitivity to CRH in both males and females. E and PF males
      demonstrated increased plasma ACTH but not CORT compared with C males, whereas E
      females demonstrated increased plasma ACTH and CORT levels compared with PF and C
      females after CRH infusion. CONCLUSIONS: Together these data suggest that (1) E
      animals do not show increased adrenal sensitivity to ACTH compared with controls;
      (2) the insult of prenatal ethanol exposure may result in altered pituitary
      sensitivity to CRH after DEX suppression; and (3) there may be a sex-specific
      difference in sensitivity of the mechanism(s) underlying HPA hyper
      responsiveness.

PMID- 10924018
TI  - Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice
      differ in sensitivity to ethanol excitation.
AB  - BACKGROUND: The mesolimbic dopamine pathway that originates in the ventral
      tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol
      has been shown to excite dopaminergic neurons of the VTA, both in vivo and in
      vitro, in rats. Behavioral differences in the rewarding effects of ethanol have
      been observed between C57BL/6J and DBA/2J mice. The present electrophysiological
      study examined the effect of ethanol on individual dopaminergic VTA neurons from
      these two inbred mouse strains. METHODS: Extracellular single unit recordings of
      spontaneous action potentials were made from dopaminergic VTA neurons in brain
      slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was
      administered in the superfusate and the mean change in firing rate produced by
      ethanol was measured. RESULTS: There was no significant difference in basal
      spontaneous firing rate of dopaminergic VTA neurons between these two mouse
      strains. Ethanol caused a concentration-dependent increase in the firing rate of
      neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from
      DBA/2J mice more potently than those from C57BL/6J mice. CONCLUSIONS: The
      difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in
      C57BL/6J and DBA/2J mice may contribute to differences in their behavioral
      response to ethanol. The fact that a given concentration of ethanol causes
      greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in
      C57BL/6J mice could explain why DBA/2J mice show much stronger place preference
      conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J
      mice may be partly due to the insensitivity of their dopaminergic VTA neurons
      that requires them to drink a lot of ethanol to achieve sufficient excitation of
      reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its
      rewarding effect, because of their aversion to its taste.

PMID- 10924019
TI  - Congenital and metabolic myopathies of childhood or adult onset.
AB  - OBJECTIVES: To investigate the clinical presentation, histological findings, and
      outcome of patients with congenital and metabolic myopathies (CM and MM) in whom
      the disease was diagnosed in childhood or adulthood. PATIENTS AND METHODS: We
      reviewed the diagnosis of all skeletal muscle biopsies performed by our group
      between 1984 and 1996 (13 years). All patients with CM and MM of childhood or
      adult onset were included in the study. Patients with mitochondrial myopathies
      were excluded because they are multisystemic disorders with a more distinct
      picture than that observed in other MM. We retrospectively reviewed the clinical
      history, with special emphasis on the clinical patterns of presentation,
      histological findings, and outcome. RESULTS: Among 1,865 biopsies, 28 (1.5%)
      fulfilled the diagnostic criteria for CM (seven nemaline myopathies, four
      multicore myopathies, three centronuclear myopathies) or MM (five adult-onset
      acid maltase deficiency, three myophosphorylase deficiency, three
      phosphofructokinase deficiency, two carnitine palmitoyl transferase deficiency,
      and one carnitine deficiency). In nearly half of the patients, mild stable
      weakness was the major complaint, whereas in one third muscular symptoms were
      intermittent and related to exercise. In a small number of cases, a persistently
      raised serum creatine kinase in an asymptomatic patient was the reason for muscle
      biopsy. Histological examination of skeletal muscle was highly indicative of a
      specific muscle disease in 26 of the 28 cases. After a mean follow-up of 7 years,
      the outcome has generally been good, and in most patients the myopathy did not
      worsen, most remaining ambulatory. CONCLUSION: CM and MM presenting in childhood
      or adulthood are infrequent; the symptoms are usually mild or moderate, and the
      prognosis generally is good.

PMID- 10924020
TI  - Incidence of occult cancer in children presenting with musculoskeletal symptoms:
      a 10-year survey in a pediatric rheumatology unit.
AB  - OBJECTIVES: To assess the frequency and types of cancer found in children
      presenting to our Unit with musculoskeletal symptoms over a 10-year period.
      METHODS: The medical records of patients with musculoskeletal symptoms and a
      final diagnosis of cancer were reviewed. In each case age, gender, presenting
      symptoms, laboratory data, diagnostic procedures, provisional and final
      diagnoses, and time between clinical onset and correct diagnosis were reviewed.
      RESULTS: An underlying neoplasia was found in 10 of 1,254 patients (<1%)
      complaining of musculoskeletal symptoms. The types of malignancies found included
      acute lymphocytic leukemia (ALL) (6 cases), lymphoma (2 cases), neuroblastoma (1
      case), and Ewing's sarcoma (1 case). The mean time between disease onset and
      final diagnosis was 3.2 months. The most common presenting feature was
      monoarthritis, involving the larger joints such as the elbows, knees or ankles.
      Juvenile idiopathic arthritis (JIA) was the most frequent provisional diagnosis.
      In the preliminary hematologic evaluation, eight patients had an increased
      erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) value. White
      blood cell (WBC) count was normal in almost all children, with a normal
      differential count. Lactic dehydrogenase (LDH) was raised in all children. Bone
      marrow aspirates and lymph node or bone biopsies were necessary to reach the
      final diagnosis. CONCLUSIONS: A malignancy should always be excluded in children
      with musculoskeletal symptoms, especially when the clinical pattern is not
      characteristic of a specific rheumatic disease. Routine laboratory tests may be
      misleading. The simultaneous presence of high LDH or alpha-hydroxybutyric
      dehydrogenase (alpha-HBDH) levels and raised ESR or CRP, even with normal blood
      cell counts, should lead to additional investigations. RELEVANCE: All patients
      presenting with arthritis or other musculoskeletal symptoms should have a
      thorough clinical examination. Disproportionate pain levels and an atypical
      pattern of "arthritis," especially in the presence of systemic manifestations,
      suggest a possible underlying malignancy.

PMID- 10924021
TI  - Adult Henoch-Schonlein purpura associated with malignancy.
AB  - OBJECTIVE: Malignancies are among the well-established causes of vasculitis. We
      studied the association between adult Henoch-Schonlein purpura (HSP) and
      malignant neoplasms. METHODS: We retrospectively reviewed 14 cases of adult HSP
      diagnosed during a 6-year period and found a malignant neoplasm in four. Fifteen
      reports of adult HSP with malignant disease were identified in the literature.
      These 19 cases were compared with 158 adults who had HSP but no malignancy and
      who where reported in the literature. RESULTS: Most (63%) of the malignant
      neoplasms associated with adult HSP were solid tumors: lung, n = 6; prostate, n =
      2; breast, n = 1; renal, n = 1; stomach, n = 1; and small bowel, n = 1.
      Hematologic malignancies (37%) included non-Hodgkin lymphoma, n = 2; Hodgkin
      disease, n = 2; IgA multiple myeloma, n = 1; myeloproliferative disease, n = 1;
      and myelodysplastic syndrome, n = 1. Patients with malignancy were older (median
      age, 59 years), were more likely to be male (M/F = 8.5), had joint involvement
      more frequently (95%), and had a lower frequency of prior acute infection than
      those without malignancy. A typical paraneoplastic course was documented in only
      two cases. CONCLUSIONS: Epidemiological studies are needed to determine the
      association between adult HSP and malignancy. In practice, it may be wise to
      suspect a malignancy in men older than 40 years of age who develop HSP in the
      absence of a precipitating factor. Pathogenic hypotheses involve tumor antigens
      or abnormal IgA production leading to immune complex formation.

PMID- 10924022
TI  - Necrotizing small-vessel vasculitis confined to the uterine cervix.
AB  - OBJECTIVES: To report our experience with five cases of apparently isolated small
      vessel vasculitis of the uterine cervix. METHODS: Case study of five patients
      with necrotizing vasculitis discovered incidentally in surgical specimens of the
      female genital tract, and a review of the pertinent literature on this subject.
      RESULTS: All patients lacked clinical and serological features of the well
      delineated vasculitic syndromes. Comprehensive workup failed to yield any
      evidence of an underlying disorder. All patients were managed expectantly and did
      not develop systemic vasculitis during follow-up ranging from 6 months to 5
      years. CONCLUSIONS: Isolated vasculitis of the female genital tract can be
      encountered as an innocuous finding in otherwise healthy individuals. The cause
      and pathogenesis of this disorder remain obscure. Rheumatologists should be
      familiar with this rare and vexing form of vasculitis and with its benign
      prognosis.

PMID- 10924023
TI  - Cytopenia and past human parvovirus B19 infection in patients with primary
      Sjogren's syndrome.
AB  - OBJECTIVES: To determine the clinical significance of human parvovirus B19
      infection in patients with primary Sjogren's syndrome (SS) and to investigate the
      immunologic and hematologic features related to B19 infection. METHODS: We
      included 80 consecutive patients with primary SS (74 women and 6 men), with a
      mean age of 62 years (range, 24 to 87 years) that were seen in our Unit. All
      patients fulfilled the European Community criteria for SS. As controls, we
      included 140 consecutive sera samples analyzed for B19 antibodies in our
      Microbiology Department and obtained from adult inpatients and outpatients of our
      Hospital. Serum from all patients and controls was tested for antibodies to B19
      by enzyme-linked immunosorbent assay (ELISA). Additionally, the presence of B19
      DNA in serum and in circulating leukocytes was investigated by nested polymerase
      chain reaction (PCR). RESULTS: Serological evidence of past B19 infection
      (positive IgG antibodies without IgM antibodies) was present in 28 (35%) patients
      with primary SS. None of these patients showed evidence for B19 viremia, and B19
      virus DNA was not detected in the circulating leukocytes of IgG-B19(+) patients.
      Positivity for IgM antibodies to B19 was not detected in any patient. When
      compared with patients without evidence of past B19 infection, those with primary
      SS and past B19 infection showed a higher prevalence of cytopenia (57% v 15%; P <
      .001), and, specifically, of leukopenia (36% v 4%; P < .001). Additionally, when
      compared with controls positive for IgG-B19, SS patients with these antibodies
      had a higher prevalence of cytopenia (57% v 13%; P < .001), leukopenia (36% v 3%;
      P < .001) and thrombocytopenia (21% v 0%; P = .003). CONCLUSIONS: Serological
      evidence of past B19 infection is associated with the presence of cytopenia in
      our patients with primary SS. A possible relationship between B19 infection and
      the presence of cytopenia in primary SS may occur in some patients
      immunologically or genetically predisposed.

PMID- 10924024
TI  - Sonographic imaging of the distal phalanx.
AB  - OBJECTIVE: To investigate the potential role of ultrasonography (US) with very
      high frequency transducers in assessing distal phalanx involvement in some
      rheumatic diseases. METHODS: We performed sonographic evaluation with an Esaote
      AU-4 Idea (Esaote Biomedica, Genoa, Italy) equipped with a 13-MHz linear
      transducer. The images were obtained in asymptomatic healthy subjects and
      representative patients with psoriatic arthritis, osteoarthritis of the distal
      interphalangeal joint (Heberden's nodes), erosive osteoarthritis, gout,
      rheumatoid arthritis, systemic sclerosis, and posttraumatic synovial cyst.
      RESULTS: US with very high frequency transducers allowed a careful identification
      of the following anatomic details: joint space, extensor and flexor tendons, bone
      margin, periarticular and peritendinous soft tissues, nail, and blood vessels.
      Several pathological changes were depicted in different rheumatic disorders.
      These included joint space widening, tendon sheath widening, dislocation of the
      joint surfaces, irregularity of the bone margin, and urate and calcium deposits
      within periarticular soft tissues. CONCLUSIONS: Very high frequency US is able to
      depict the anatomic substrate of distal phalanx involvement in several rheumatic
      diseases, adding useful information to clinical examination of the hand.

PMID- 10924025
TI  - The pathogenesis of autoimmunity in New Zealand mice.
AB  - OBJECTIVE: New Zealand mice were the first spontaneous animal model of human
      systemic lupus erythematosus (SLE). Since their initial discovery in 1959,
      studies of these mice have provided insights into the immunopathogenesis and
      genetics of lupus and have had a substantial impact on our understanding of
      autoimmunity. METHODS: We extensively reviewed published data for the past 40
      years, including work in cellular immunology and molecular biology, to provide
      new information on the role of lymphoid subpopulations, cytokines, costimulatory
      molecules, apoptosis, and genetic susceptibility in the natural history of
      immunopathology in murine lupus. RESULTS: Genetic factors constitute the most
      important contribution to autoimmunity in New Zealand mice, and specific major
      susceptibility loci have been described. In addition, there is evidence for a
      pluripotent stem cell defect, which has implications for developmental and
      functional defects of T and B cells. The end result of these defects is a
      breakdown of self-tolerance and production of autoantibodies. Further studies
      will undoubtedly shape our understanding of this murine model and provide the
      basis for novel diagnostic and therapeutic approaches in humans. CONCLUSIONS: The
      advent of molecular biology, including the use of monoclonal antibody therapy in
      New Zealand mice, has been instrumental in our understanding of the loss of self
      tolerance in SLE. Finally, identification of genetic susceptibility loci in the
      murine system has also led to important comparable studies in humans with SLE.
      RELEVANCE: The observations in New Zealand mice are of particular importance to
      systemic lupus erythematosus (SLE).

PMID- 10924026
TI  - Measuring health status in Israeli patients with fibromyalgia syndrome and
      widespread pain and healthy individuals: utility of the short form 36-item health
      survey (SF-36).
AB  - OBJECTIVES: To examine the usefulness of the Medical Outcomes Study Short Form-36
      (MOS SF-36) in measuring health-related quality of life (QOL) in fibromyalgia
      syndrome (FMS) patients, and to determine whether subscale scores of SF-36 could
      distinguish patients with FMS from patients with widespread pain alone, and from
      healthy individuals. METHODS: The study population included three groups of
      women: 90 patients with FMS, 96 patients with widespread pain, and 50 healthy
      controls. In all subjects, health-related QOL was assessed by SF-36. The Health
      Assessment Questionnaire was used to evaluate functional disability, helplessness
      and psychological status. FMS-related symptoms and tenderness also were assessed.
      RESULTS: The 8 subscales of SF-36 showed a consistent pattern for physical
      function, physical role functioning, body pain, general health, vitality, and
      social function, with the lowest scores in patients with FMS, intermediate scores
      in patients with widespread pain alone, and the highest scores in healthy
      subjects. Emotional role functioning and mental health scores were significantly
      higher among healthy controls than among patients. The SF-36 subscales of
      physical functioning, bodily pain, and social functioning were highly correlated
      with another measure of functional disability (from the Health Assessment
      Questionnaire) in all patient groups. Most of the subscales were associated with
      psychological variables (helplessness, depression, and anxiety). All eight
      subscales of SF-36 were strongly correlated with the mean score of another
      measure of quality of life, QOL-16. CONCLUSIONS: Most of the SF-36 subscales
      represent health dimensions relevant to patients with FMS and widespread pain
      alone. The severity of functional impairment as assessed by the SF-36,
      distinguishes patients with FMS and widespread pain alone from healthy
      individuals, and also discriminates between patients with widespread pain alone
      and FMS patients.

PMID- 10924027
TI  - Does social medicine still matter in an era of molecular medicine?
AB  - To ask whether social medicine still matters may seem to be in poor taste at a
      symposium to honor Martin Cherkasky, but social medicine has always had the
      courage to take on difficult questions. There is all the more reason to do so
      when its legitimacy is challenged. The extraordinary findings emerging from the
      human genome project will revolutionize diagnostic and therapeutic methods in
      medicine. The power of medical interventions, for good and for harm, will
      increase enormously. However, in the next millennium, as in this one, social
      factors will continue to be decisive for health status. The distribution of
      health and disease in human populations reflects where people live, what they
      eat, the work they do, the air and the water they consume, their activity, their
      interconnectedness with others, and the status they occupy in the social order.
      Virchow's aphorism is as true today as it was in 1848: "If disease is an
      expression of individual life under unfavorable conditions, then epidemics must
      be indicative of mass disturbances of mass life." Increasing longevity resulting
      from major economic transformations has made ours the age of chronic disease.
      Changes in diet and behavior transform genes that once conferred selective
      biologic advantage into health hazards. Although disease risk varies with social
      status, medical care makes an important difference for health outcomes. Access to
      care and the quality of care received are functions of social organization, the
      way care is financed, and political beliefs about the "deserving" and the
      "underserving" poor. It is a moral indictment of the US that ours is the only
      industrialized society without universal health care coverage. In educating the
      American public about the social determinants of health, a goal Martin Cherkasky
      championed, the very power of the new molecular biology will help make our case.
      Social medicine is alive and well.

PMID- 10924028
TI  - Decisions about access to health care and accountability for reasonableness.
AB  - Insurers make decisions that directly limit access to care (e.g., when deciding
      about coverage for new technologies or formulary design) and that indirectly
      limit access (e.g., by adopting incentives to induce physicians to provide fewer
      or different services). These decisions raise questions about legitimacy and
      fairness. By holding health plans accountable for the reasonableness of their
      decisions, it is possible to address these questions. Accountability for
      reasonableness involves providing publicly accessible rationales for decisions
      and limiting rationales to those that all "fair-minded" persons can agree are
      relevant to meeting patient needs fairly under resource constraints. This form of
      accountability is illustrated by examining its implications for the three
      examples of direct and indirect limit setting noted here.

PMID- 10924029
TI  - Crisis, leadership, consensus: the past and future federal role in health.
AB  - This paper touches on patterns of federal government involvement in the health
      sector since the late 18th century to the present and speculates on its role in
      the early decades of the 21st century. Throughout the history of the US,
      government involvement in the health sector came only in the face of crisis, only
      when there was widespread consensus, and only through sustained leadership. One
      of the first health-related acts of Congress came about as a matter of interstate
      commerce regarding the dilemma as to what to do about treating merchant seamen
      who had no affiliation with any state. Further federal actions were implemented
      to address epidemics, such as from yellow fever, that traveled from state to
      state through commercial ships. Each federal action was met with concern and
      resistance from states' rights advocates, who asserted that the health of the
      public was best left to the states and localities. It was not until the early
      part of the 20th century that a concern for social well-being, not merely
      commerce, drove the agenda for public health action. Two separate campaigns for
      national health insurance, as well as a rapid expansion of programs to serve the
      specific health needs of specific populations, led finally to the introduction of
      Medicaid and Medicare in the 1960s, the most dramatic example of government
      intervention in shaping the personal health care delivery system in the latter
      half of the 20th century. As health costs continued to rise and more and more
      Americans lacked adequate health insurance, a perceived crisis led President
      Clinton to launch his 1993 campaign to insure every American--the third attempt
      in this century to provide universal coverage. While the crisis was perceived by
      many, there was no consensus on action, and leadership outside government was
      missing. Today, the health care crisis still looms. Despite an economic boom, 1
      million Americans lose their health insurance each year, with 41 million
      Americans, or 15% of the population, lacking coverage. Private premiums are going
      up again as federal programs are capped and the lack of a federal framework for
      quality assurance leads to growing problems of access and quality that will need
      to be addressed as we enter the 21st century. What role will government play?

PMID- 10924030
TI  - The role of academic health systems in promoting population health.

PMID- 10924031
TI  - Challenges for the public in negotiating the health system in the 21st century.
AB  - This paper addresses the challenges and opportunities that face the public in
      negotiating the health care system (both medicine and public health) in the 21st
      century. It addresses three issues: how consumers exercise choice, with special
      attention to the choice of health care coverage; how patients and communities
      interact with clinicians and public health professionals; and whether and how the
      public's "voice" is heard as health policy decisions, at the societal and
      institutional levels, are made. With respect to each of these issues, the paper
      describes the current status of public influence and articulates a vision for the
      future. These three related visions are (1) that empowered, informed, supported
      consumers make decisions about health plans, clinicians, treatments, and their
      own behavior; (2) that clinicians and public health professionals, working as
      partners with patients and communities, are in a position to "standardize the
      customization of care" so that all aspects of care are tailored to the needs of
      the individual, family, or community in question and social, economic, and
      cultural factors are taken into account in the day-to-day practice of medicine
      and public health; and (3) that the ability and willingness of the public to
      negotiate and shape the health care environment is supported by an independent
      infrastructure that permits enhanced public involvement in health policy making
      and governance. The paper identifies key elements of this vision, discusses
      challenges to pursuing and achieving each vision, and identifies opportunities
      that may support the pursuit of the vision.

PMID- 10924032
TI  - The future of social medicine.
AB  - The future of social medicine is based on 150 years of history and the rapidly
      evolving context within which medicine functions in modern societies. There are
      two views of social medicine. One is based on the vision of Guerin and,
      particularly, Virchow 150 years ago that: "Doctors are the natural advocates of
      the poor, and social problems are largely within their jurisdiction." The New
      York Academy of Medicine's Institute on Social Medicine 50 years ago reflected
      this broad view. Medicine, however, enamored of the biomedical paradigm and the
      advances in knowledge through biomedical research, largely abandoned this broad
      perspective, even as the knowledge about the social, behavioral, and
      environmental determinants of health was advancing rapidly. A second view of
      social medicine, and one that has influenced many in the past 30 years, was
      defined by McKeown and Lowe: "Social medicine is concerned with a body of
      knowledge and methods of obtaining knowledge appropriate to a discipline. This
      discipline may be said to comprise (a) epidemiology, and (b) the study of the
      medical needs of society, or in the contemporary short hand medical care." Social
      medicine, in my view, includes not only the definition of McKeown and Lowe, but
      the broader context within which medicine fits in society. The context is
      changing. The social contract as defined by Bismarck and Beveridge has to be
      redefined. Just as the New York Academy of Medicine provided the vision of social
      medicine 50 years ago, the Academy has given us a new vision with the publication
      of Medicine and Public Health: the Power of Collaboration in 1997. Authored by
      Dr. Roz Lasker, director of the Academy's Division of Public Health, the book
      identifies the key changes required by medicine and public health to advance the
      goals of medicine and public health for the benefit of both individual patients
      and the population as a whole. The book points the way for the future of social
      medicine by identifying not only what needs to be done, but also how to do it.

PMID- 10924033
TI  - Gender differences in HIV risk behaviors in an adult emergency department in New
      York City.
AB  - BACKGROUND: The human immunodeficiency virus (HIV) epidemic in the US
      increasingly involves urban heterosexual adults, particularly women, belonging to
      ethnic minority groups. An understanding of gender-based differences in HIV risk
      behaviors within these groups would be of value in the ongoing struggle to limit
      HIV transmission in metropolitan centers. METHODS: This was a prospective study
      of demographic and historical characteristics and HIV risk behaviors. The study
      utilized a structured interview format, which was administered to all patients
      treated by participating emergency department physicians. RESULTS: On univariate
      analysis of data obtained from 1,460 patients who had neither a known HIV
      infection nor a chief complaint or final emergency department diagnosis
      associated with HIV risk behaviors, men were more likely to be older, homeless,
      to have ever injected drugs, used crack, engaged in same-gender sex, paid for
      sex, been incarcerated, or had syphilis or gonorrhea. Women were more likely to
      report prior chlamydia infection or to report that their sole sex partners had
      other partners within the past year. On multivariate analysis, variables
      independently associated with male gender included homelessness, injection drug
      use, crack use, any prior sexually transmitted disease (in subjects 35 years of
      age or older), and sex with prostitutes. In a separate analysis of patients
      admitting to drug use, the male predominance of other risk behaviors was not
      observed; the only significant differences between genders were a higher rate of
      prostitution among women and a higher rate of sexual contact with a prostitute
      among men. CONCLUSIONS: In patients visiting an inner-city emergency department
      in the Bronx, HIV risk behaviors are generally more common in men, but rates of
      risk behaviors among male and female drug users are comparable.

PMID- 10924034
TI  - Strategies to increase enrollment in children's health insurance programs: a
      report of the New York Academy of Medicine.

PMID- 10924035
TI  - Blindness and high suicide risk?

PMID- 10924036
TI  - Effects of color temperature of fluorescent lamps on body temperature regulation
      in a moderately cold environment.
AB  - A study on the effects of different color temperatures of fluorescent lamps on
      skin and rectal temperatures in a moderately cold environment involving (i)
      changes in skin temperature of 7 male subjects exposed to an ambient temperature
      ranging from 28 degrees C to 18 degrees C (experiment I) and (ii) changes in skin
      and rectal temperatures and metabolic heat production of 11 male subjects exposed
      to ambient temperature of 15 degrees C for 90 min (Experiment II) was conducted.
      In Experiment I, the reduction of mean skin temperature from the control value
      was significantly greater under 3000 K than under 5000 K or 7500 K lighting. In
      Experiment II, the reductions in mean skin temperature and rectal temperature
      were respectively greater and smaller under 3000 K than those under 5000 K or
      7500 K lighting. However, metabolic heat production was not affected by color
      temperature conditions. The relationships between morphological and physiological
      parameters revealed that no significant relation of rectal temperature to body
      surface area per unit body weight was found only under 3000 K. Furthermore, while
      the mean skin temperature was independent on the mean skinfold thickness under
      3000 K, a significant negative correlation between the rectal and mean skin
      temperatures was observed. Therefore, body heat loss might be suppressed
      effectively by increasing the vasoconstrictor tone under a color temperature of
      3000 K, and the body shell was dependent only on morphological factors under 5000
      K and 7500 K lighting.

PMID- 10924037
TI  - The effect of mental loads on muscle tension, blood pressure and blink rate.
AB  - Surface electromyogram (EMG), blood pressure (BP), blink rate (BR) and heart rate
      (HR) were recorded before and during 4 types of mental task. The mental task
      involved 3 tasks that encompassed the memory (M), visual search (VS) and color
      word (CW) tasks besides the control task (CT) of maintaining a similar posture
      while focusing on a single spot on the computer screen. Except for CW, any
      voluntary movement for response to visual stimuli given were not demanded.
      Slightly but significant increases in integrated EMG (iEMG) were shown in
      terapezius, biceps and gastrocnemius muscles during tasks except for CT.
      Especially in the trapezius muscle during M, the most remarkable enhancements of
      iEMG and BP were shown. In VS and CW tasks, significant decreases in BR were
      observed, although in M and CT tasks there were no significant changes in it.
      There were no significant changes in HR in any type of tasks. The present study
      demonstrated the increase in muscle tension due to mental needs of cognitive
      tasks per se accompanying changes in BP and BR. And, enhancement of these
      physiological responses by memory loads and eyeball movement was discussed as a
      possible mechanism.

PMID- 10924039
TI  - The effects of skin pressure by clothing on whole gut transit time and amount of
      feces.
AB  - The experiment investigated the effects of skin pressure by clothing on whole gut
      transit time and amount of feces. Comparisons of transit time and amount of feces
      were taken between 6 young female adults with and without a girdle. The skin
      pressure applied by a girdle (mean +/- SD) on participant's waist, abdomen and
      hip region was 16.6 +/- 7.80 mmHg, 17.1 +/- 4.5 mmHg and 12.6 +/- 5.0 mmHg,
      respectively. The difference of skin pressure with and without a girdle was about
      10 mmHg. During each experimental period of 4 days with and without a girdle, the
      whole gut transit time and amount of feces were measured. The whole gut transit
      time of each day was determined as the time between the oral intake of each day's
      markers and their first appearance in the stool. The whole gut transit times of
      the markers taken on the first day were significantly prolonged (p < 0.05) and
      those of the markers taken on the second day tended to be prolonged for
      participant using a girdle (p < 0.1). The whole gut transit time of the markers
      taken on the third day could not be compared because they were not excreted into
      the stool. The cumulative increases of feces on the third day and the fourth day
      were significantly reduced with a girdle (p < 0.05). These results indicate that
      the skin pressure by clothing has an effect on whole gut transit time and the
      amount of feces.

PMID- 10924038
TI  - Effect of resistive knee extension training on postural control measures in
      middle aged and elderly persons.
AB  - The purpose of the present study was to determine whether knee extension strength
      gain in middle-aged and elderly persons is associated with improvement in the
      limits of stability when leaning his/her body in various directions. The
      resistance training group (EXT; 4 males, 17 females) completed two bilateral knee
      extension training sessions, consisting of one set of exercises, per week for 10
      weeks. The non-training control group (CONT; 4 males, 3 females) were instructed
      not to train their legs during the 10-week control period. One set of exercises
      consisted of 8-12 repetitions of a dynamic resistance exercise until volitional
      fatigue for knee extension. The initial load for training was set at 70% of the
      one-repetition maximum (1-RM). The thickness of the rectus femoris (RF) and
      vastus lateralis (VL) muscles were measured using a B-mode ultrasound apparatus.
      The postural control measures, obtained using the Balance Master system, included
      the percentage limits-of-stability (%LOS) and path length (%Path). The 1-RM in
      EXT was increased significantly by resistance training (p < 0.001). In addition,
      significant differences were observed between the percentage increase of 1-RM in
      EXT and those in CONT at wk 5 and at wk 10 of resistance training (p < 0.001).
      However, no significant increase in muscle thickness of RF or VL was found in
      EXT. The %LOS to the rear target in EXT was increased significantly by resistance
      training (p < 0.05-0.01). In addition, the percentage change in %Path was
      decreased significantly by resistance training (p < 0.001). Therefore, strength
      gain in quadriceps femoris appears to be associated with improvement in the %LOS
      and %Path for the rear. In conclusion, strength gain in quadriceps femoris is
      thought to possibly enable accurate movement of the COG farther from the center
      target towards the rear, suggesting that strength gain has a positive influence
      on a person's perception of their ability to avoid falls.

PMID- 10924040
TI  - Effects of skin pressure by clothing on digestion and orocecal transit time of
      food.
AB  - In order to reveal the influence of clothing skin pressure on digestion of food
      through the gastrointestinal tract, we examined the absorption of dietary
      carbohydrate and orocecal transit time of a test meal by means of a breath
      hydrogen test on 7 healthy young women. In this experiment, we collected breath
      samples from the participants wearing loose-fitting experimental garment on the
      second day of the experiment and from the same participants but wearing an
      additional tight-fitting girdle on the following day for 16 hours and 9 hours,
      respectively. Skin pressure applied by a girdle on participant's waist, abdomen
      and hip region was 15.5 +/- 0.4 mmHg (mean +/- SE), 11.0 +/- 0.2 mmHg, and 13.6
      +/- 0.6 mmHg, respectively, and the values were 2-3 times larger than those of
      the experimental garment. The hydrogen concentration vs. time curve showed that
      breath hydrogen levels at its peaks (15:00, 15:30, 16:00, 16:30, and 17:00 hr) on
      the third day of the experiment were significantly higher than those of the
      corresponding time on the second day (p < 0.05 at 17:00 and 15:00, p < 0.01 at
      15:00, 16:00 and 16:30). Consequently, significantly pronounced breath hydrogen
      excretion was observed under the "pressure" clothing condition (p < 0.01). On the
      other hand, the transit time of the test meal for the subjects wearing a girdle
      did not differ significantly from that for the subjects wearing the garment of
      less pressure (270 +/- 18 minutes and 263 +/- 21 minutes, respectively). These
      results indicate that the clothing skin pressure has an inhibitory effect on the
      absorption of dietary carbohydrate in the small intestine, but no effect on the
      orocecal transit time of a meal.

PMID- 10924041
TI  - Impact factors and the competitive nature of journal publishing

PMID- 10924042
TI  - Nitric oxide exerts feedback inhibition on EDHF-induced coronary arteriolar
      dilation in vivo.
AB  - We tested the hypothesis that nitric oxide (NO) inhibits endothelium-derived
      hyperpolarizing factor (EDHF)-induced vasodilation via a negative feedback
      pathway in the coronary microcirculation. Coronary microvascular diameters were
      measured using stroboscopic fluorescence microangiography. Bradykinin (BK)
      induced dilation was mediated by EDHF, when NO and prostaglandin syntheses were
      inhibited, or by NO when EDHF and prostaglandin syntheses were blocked.
      Specifically, BK (20, 50, and 100 ng. kg(-1). min(-1) ic) caused dose-dependent
      vasodilation similarly before and after administration of N(G)-monomethyl-L
      arginine (L-NMMA) (3 micromol/min ic for 10 min) and indomethacin (Indo, 10 mg/kg
      iv). The residual dilation to BK with L-NMMA and Indo was completely abolished by
      suffusion of miconazole or an isosmotic buffer containing high KCl (60 mM),
      suggesting that this arteriolar vasodilation is mediated by the cytochrome P-450
      derivative EDHF. BK-induced dilation was reduced by 39% after inhibition of EDHF
      and prostaglandin synthesis, and dilation was further inhibited by combined
      blockade with L-NMMA to a 74% reduction in the response. This suggests an
      involvement for NO in the vasodilation. After dilation to BK was assessed with L
      NMMA and Indo, sodium nitroprusside (SNP, 1-3 microgram. kg(-1). min(-1) ic), an
      exogenous NO donor, was administered in a dose to increase the diameter to the
      original control value. Dilation to BK was virtually abolished when administered
      concomitantly with SNP during L-NMMA and Indo (P < 0.01 vs. before SNP),
      suggesting that NO inhibits EDHF-induced dilation. SNP did not affect adenosine-
      or papaverine-induced arteriolar dilation in the presence of L-NMMA and Indo,
      demonstrating that the effect of SNP was not nonspecific. In conclusion, our data
      are the first in vivo evidence to suggest that NO inhibits the production and/or
      action of EDHF in the coronary microcirculation.

PMID- 10924043
TI  - A comparison of transient outward currents in canine cardiac Purkinje cells and
      ventricular myocytes.
AB  - Although abnormalities in Purkinje cell (PC) repolarization are important causes
      of cardiac arrhythmias, the detailed properties of repolarizing currents in PCs
      are incompletely understood. We compared transient outward K(+) current (I(to))
      in single PCs from canine false tendons with midmyocardial ventricular myocytes
      (VMs). I(to) reactivation was biexponential, with a similar rapid-phase time
      constant (30 +/- 5 and 35 +/- 4 ms for VM and PC, respectively) but a large, slow
      component in PCs with a much greater time constant than VM (1,427 +/- 70 vs. 181
      +/- 24 ms, P < 0.001). Tetraethylammonium had no effect on VM I(to) but
      reversibly inhibited PC I(to) (IC(50) = 2.4 +/- 0.4 mM). PC I(to) was also more
      sensitive to 4-aminopyridine (IC(50) = 50 +/- 7 vs. 526 +/- 49 microM in VM, P <
      0.0001). H(2)O(2) slowed I(to) inactivation in PCs but did not affect VM I(to).
      We conclude that PC I(to) shows significant differences from VM I(to), with some
      features, such as tetraethylammonium sensitivity, that have been reported in
      neither cardiac I(to) of atrial or ventricular myocytes nor cloned K(+) channel
      subunits (Kv1.4, Kv4.2, or Kv4.3) known to participate in cardiac I(to).

PMID- 10924045
TI  - Arteriolar wall PO(2) and nitric oxide release during sympathetic
      vasoconstriction in the rat intestine.
AB  - Endothelium-derived nitric oxide (NO) attenuates arteriolar constriction in the
      rat small intestine during periods of increased sympathetic nerve activity. This
      study was undertaken to test the hypothesis that a flow-dependent fall in
      arteriolar wall PO(2) serves as the stimulus for endothelial NO release under
      these conditions. Sympathetic nerve stimulation at 3-16 Hz induced frequency
      dependent arteriolar constriction, with arteriolar wall O(2) tension (PO(2))
      falling from 67 +/- 3 mmHg to as low as 41 +/- 6 mmHg. Arteriolar responses to
      nerve stimulation were enhanced after inhibition of NO synthase with N(G)
      monomethyl-L-arginine (L-NMMA). Under a high-O(2) (20%) superfusate, the fall in
      wall PO(2) was significantly attenuated, arteriolar constrictions were increased
      by 57 +/- 9 to 66 +/- 12%, and these responses were no longer sensitive to L
      NMMA. The high-O(2) superfusate had no effect on vascular smooth muscle
      responsiveness to NO (as judged by arteriolar responses to sodium nitroprusside)
      or on arteriolar wall oxidant activity (as determined by the reduction of
      tetranitroblue tetrazolium dye). These results indicate that a flow-dependent
      fall in arteriolar wall PO(2) may serve as a stimulus for the release of
      endothelium-derived NO during periods of increased sympathetic nerve activity.

PMID- 10924044
TI  - H(2)O(2) opens BK(Ca) channels via the PLA(2)-arachidonic acid signaling cascade
      in coronary artery smooth muscle.
AB  - H(2)O(2) is a reactive oxygen species that contracts or relaxes vascular smooth
      muscle, but the molecular basis of these effects remains obscure. We previously
      demonstrated that H(2)O(2) opens the large-conductance, calcium- and voltage
      activated (BK(Ca)) potassium channel of coronary myocytes (2) and now report
      physiological and biochemical evidence that the effect of H(2)O(2) on coronary
      smooth muscle involves the phospholipase A(2) (PLA(2))/arachidonic acid (AA)
      signaling cascades. H(2)O(2) stimulation of BK(Ca) channel activity was inhibited
      by arachidonyl trifluoromethyl ketone, an inhibitor of cytosolic PLA(2).
      Furthermore, H(2)O(2) stimulated release of [(3)H]AA from coronary myocytes, and
      exogenous AA mimicked the effect of H(2)O(2) on BK(Ca) channels. Inhibitors of
      protein kinase C activity attenuated the effect of H(2)O(2) on BK(Ca) channels,
      [(3)H]AA release, or intact coronary arteries. In addition, the effect of
      H(2)O(2) or AA on BK(Ca) channels was inhibited by blockers of lipoxygenase
      metabolism. In contrast, inhibitors of cyclooxygenase or cytochrome P-450 had no
      effect. We propose that H(2)O(2) relaxes coronary arteries by stimulating BK(Ca)
      channels via the PLA(2)/AA signaling cascade and that lipoxygenase metabolites
      mediate this response.

PMID- 10924046
TI  - PKC-dependent delayed metabolic preconditioning is independent of transient MAPK
      activation.
AB  - In this study we used an in vitro model of delayed preconditioning to investigate
      activation of mitogen-activated protein kinases (MAPKs) and their potential role
      in protection. Neonatal rat cardiomyocytes were preconditioned using a buffer
      containing glycolytic inhibitors and low pH (minimal metabolic preconditioning;
      MMPC) consisting of modified Krebs buffer, 10 mM 2-deoxyglucose, and 20 mM
      lactate, pH 6.8, for 2 h followed by 24 h of simulated reperfusion before lethal
      simulated ischemia (LSI). MAPK activation during the MMPC protocol was determined
      using phospho-specific antisera and the effect on protection determined following
      LSI. Rapid, transient phosphorylation of extracellular signal-regulated kinases 1
      and 2 (ERK1/2) and p38 MAPK was observed during each of the MMPC, reperfusion,
      and LSI phases; an effect blocked by MAPK inhibitors PD-98059 and SB-203580,
      respectively, but not by the protein kinase C (PKC) inhibitor Ro31-8220. However,
      although MMPC was blocked by Ro31-8220, treatment with the MAPK inhibitors during
      the preconditioning protocol did not block delayed protection conferred by MMPC.
      Thus the data suggest that, in this model of delayed preconditioning, protection
      appears to be PKC dependent but independent of ERK1/2 or p38 MAPK activation.

PMID- 10924047
TI  - Acute hypoxia modulates 5-HT receptor density and agonist affinity in fetal and
      adult ovine carotid arteries.
AB  - In light of recent observations that receptor-ligand binding and coupling are
      physiologically regulated, the present study examined the hypothesis that the
      direct effects of hypoxia on vascular contractility involve modulation of
      pharmacomechanical coupling via changes in agonist affinity and/or receptor
      density. Because the direct effects of hypoxia on vascular smooth muscle
      contractility can vary with age, we carried out these experiments using both
      fetal and adult arteries. In common carotid arteries from near-term fetal and
      adult sheep, hypoxia (PO(2) = 9-12 Torr for 30 min) reduced the maximum responses
      to potassium by 17.8 +/- 3.5% (fetus) and 20.5 +/- 2.2% (adult), significantly
      reduced the pD(2) for 5-HT in the fetus (7.01 +/- 0.1 to 6.3 +/- 0.2) but not the
      adult (6.1 +/- 0.1 to 6.0 +/- 0.1), and significantly reduced 5-HT-induced
      maximum contractions (as % maximum response to 120 mM K(+)) not in the fetus
      (from 114 +/- 7 to 70 +/- 10%, not significant) but only in the adult (from 83 +/
      15 to 25 +/- 7%, P < 0.05) arteries. Hypoxia significantly attenuated 5-HT
      binding affinity (pK(A), determined by partial irreversible blockade with
      phenoxybenzamine) in both fetal (from 6.5 +/- 0.2 to 6.0 +/- 0.2) and adult
      arteries (from 6.2 +/- 0. 2 to 5.7 +/- 0.1) and also decreased receptor density
      (fmol/mg protein, determined by competitive binding with ketanserin and
      mesulergine) in adult (from 18.3 +/- 1.1 to 10.9 +/- 1.0) but not in fetal (21.0
      +/- 1.0 to 23.2 +/- 1.4) arteries. These results suggest that acute hypoxia
      modulates receptor-ligand binding via age-dependent modulation of agonist
      affinity and receptor density. These effects may contribute to hypoxic
      vasodilatation and help explain why the effects of hypoxia on vascular
      contractility differ between fetuses and adults.

PMID- 10924048
TI  - Estrogen reduces mouse cerebral artery tone through endothelial NOS- and
      cyclooxygenase-dependent mechanisms.
AB  - Gender and estrogen status are known to influence the incidence and severity of
      cerebrovascular disease. The vasoprotective effects of estrogen are thought to
      include both nitric oxide-dependent and independent mechanisms. Therefore, using
      small, resistance-sized arteries pressurized in vitro, the present study
      determined the effect of gender and estrogen status on myogenic reactivity of
      mouse cerebral arteries. Luminal diameter was measured in middle cerebral artery
      segments from males and from females that were either untreated, ovariectomized
      (OVX), or OVX with estrogen replacement (OVX + EST). The maximal passive
      diameters of arteries from all four groups were similar. In response to increases
      in transmural pressure, diameters of arteries from males and OVX females were
      smaller compared with diameters of arteries from either untreated or OVX + EST
      females. In the presence of N(G)-nitro-L-arginine methyl ester, artery diameters
      decreased in all groups, but diameters remained significantly smaller in arteries
      from males and OVX females compared with untreated and OVX + EST females. After
      endothelium removal or when inhibition of nitric oxide synthase and
      cyclooxygenase were combined, differences in diameters of arteries from OVX and
      OVX + EST were abolished. These data suggest that chronic estrogen treatment
      modulates myogenic reactivity of mouse cerebral arteries through both endothelium
      derived cyclooxygenase- and nitric oxide synthase-dependent mechanisms.

PMID- 10924049
TI  - Depressed modulation of oxygen consumption by endogenous nitric oxide in cardiac
      muscle from diabetic dogs.
AB  - Our previous study indicated that nitric oxide (NO)-dependent coronary
      vasodilation was impaired in conscious dogs with diabetes. Our goal was to
      determine whether modulation of O(2) consumption by NO is depressed in canine
      cardiac muscle after diabetes. Diabetes was induced by injection of alloxan (40
      60 mg/kg iv), dogs were killed after diabetes was induced (4-5 wk), and the
      cardiac muscle from the left ventricle was cut into 15- to 30-mg slices. O(2)
      uptake by the muscle slices was measured polarographically with a Clark-type O(2)
      electrode. S-nitroso-N-acetylpenicillamine decreased O(2) consumption in normal
      and diabetic tissues (10(-4) M, 61 +/- 7 vs. 61 +/- 8%, P > 0.05). Bradykinin
      (10(-4) M)- or carbachol (CCh, 10(-4) M)-induced inhibition of O(2) consumption
      was impaired in diabetic tissues (51 +/- 6 vs. 17 +/- 4% or 48 +/- 4 vs. 19 +/-
      3%, respectively, both P < 0.05 compared with normal). The inhibition of O(2)
      consumption by kininogen or kallikrein was depressed in diabetic tissues as well.
      In coronary microvessels from diabetic dogs, bradykinin or ACh (10(-5) M) caused
      smaller increases in NO production than those from normal dogs. Our results
      indicate that the modulation of O(2) consumption by endogenous, but not
      exogenous, NO is depressed in cardiac muscle from diabetic dogs, most likely
      because of decreased release of NO from the vascular endothelium.

PMID- 10924050
TI  - Antihypertensive properties of a nitric oxide-releasing naproxen derivative in
      two-kidney, one-clip rats.
AB  - Nonsteroidal anti-inflammatory drugs have been reported to exacerbate
      hypertension. In this study, we tested the hypothesis that a nitric oxide
      releasing derivative of naproxen would ameliorate hypertension in the rat.
      Hypertension was induced by partially occluding one renal artery (the "2K,1C"
      model), and 2 wk later the rats started receiving naproxen, the nitric oxide
      releasing derivative HCT-3012, or vehicle each day for 2 wk. Naproxen
      significantly exacerbated the hypertension. HCT-3012 significantly reduced blood
      pressure relative to both the naproxen- and vehicle-treated groups. Both naproxen
      and HCT-3012 markedly suppressed whole blood thromboxane B(2) synthesis. In
      studies of anesthetized rats, naproxen significantly enhanced the late
      hypertensive response to endothelin-1 and significantly blunted the early
      hypotensive response. In contrast, HCT-3102 did not affect either response to
      endothelin-1. In vitro, HCT-3012 significantly reduced the responsiveness of
      aortic rings to the contractile effects of phenylephrine. These studies suggest
      that HCT-3012 reduces blood pressure in hypertensive rats, not simply through the
      vasodilatory actions of the nitric oxide it releases, but through alterations in
      the responsiveness of the vasculature to endogenous pressor agents.

PMID- 10924051
TI  - Hyperventilation alters arterial baroreflex control of heart rate and muscle
      sympathetic nerve activity.
AB  - Interactions between mechanisms governing ventilation and blood pressure (BP) are
      not well understood. We studied in 11 resting normal subjects the effects of
      sustained isocapnic hyperventilation on arterial baroreceptor sensitivity,
      determined as the alpha index between oscillations in systolic BP (SBP) generated
      by respiration and oscillations present in R-R intervals (RR) and in peripheral
      sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal
      volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2
      to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P <
      0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex
      sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1
      ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased
      BP during hyperventilation does not elicit any reduction in either heart rate or
      MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation
      induced BP oscillations is attenuated. Blunted baroreflex gain during
      hyperventilation may be a mechanism that facilitates simultaneous increases in
      BP, heart rate, and sympathetic activity during dynamic exercise and
      chemoreceptor activation.

PMID- 10924052
TI  - Individualizing the aorto-radial pressure transfer function: feasibility of a
      model-based approach.
AB  - We fitted a three-segment transmission line model for the radial-carotid/aorta
      pressure transfer function (TFF) in 31 controls and 30 patients with coronary
      artery disease using noninvasively measured (tonometry) radial and carotid artery
      pressures (P(car)). Except for the distal reflection coefficient (0.85 +/- 0.21
      in patients vs. 0.71 +/- 0.25 in controls; P < 0.05), model parameters were not
      different between patients or controls. Parameters were not related to blood
      pressure, age, or heart rate. We further assessed a point-to-point averaged TFF
      (TFF(avg)) as well as upper (TFF(max)) and lower (TFF(min)) enveloping TFF. Pulse
      pressure (PP) and augmentation index (AIx) were derived on original and
      reconstructed P(car) (P(car,r)). TFF(avg) yielded closest morphological agreement
      between P(car) and P(car,r) (root mean square = 4.3 +/- 2.3 mmHg), and TTF(avg)
      best predicted PP (41.5 +/- 11.8 vs. 41.1 +/- 10.0 mmHg measured) and AIx (-0.02
      +/- 0.19 vs. 0.01 +/- 0.19). PP and AIx, calculated from P(car) or P(car,r), were
      higher in patients than in controls, irrespectively of the TFF used. We conclude
      that 1) averaged TFF yield significant discrepancies between reconstructed and
      measured pressure waveforms and subsequent derived AIx; and 2) different TFFs
      seem to preserve the information in the pressure wave that discriminates between
      controls and patients.

PMID- 10924053
TI  - Vasomotion in critically perfused muscle protects adjacent tissues from capillary
      perfusion failure.
AB  - We analyzed the incidence and interaction of arteriolar vasomotion and capillary
      flow motion during critical perfusion conditions in neighboring peripheral
      tissues using intravital fluorescence microscopy. The gracilis and semitendinosus
      muscles and adjacent periosteum, subcutis, and skin of the left hindlimb of
      Sprague-Dawley rats were isolated at the femoral vessels. Critical perfusion
      conditions, achieved by stepwise reduction of femoral artery blood flow, induced
      capillary flow motion in muscle, but not in the periosteum, subcutis, and skin.
      Strikingly, blood flow within individual capillaries was decreased (P < 0.05) in
      muscle but was not affected in the periosteum, subcutis, and skin. However,
      despite the flow motion-induced reduction of muscle capillary blood flow during
      the critical perfusion conditions, functional capillary density remained
      preserved in all tissues analyzed, including the skeletal muscle. Abrogation of
      vasomotion in the muscle arterioles by the calcium channel blocker felodipine
      resulted in a redistribution of blood flow within individual capillaries from
      cutaneous, subcutaneous, and periosteal tissues toward skeletal muscle. As a
      consequence, shutdown of perfusion of individual capillaries was observed that
      resulted in a significant reduction (P < 0.05) of capillary density not only in
      the neighboring tissues but also in the muscle itself. We conclude that during
      critical perfusion conditions, vasomotion and flow motion in skeletal muscle
      preserve nutritive perfusion (functional capillary density) not only in the
      muscle itself but also in the neighboring tissues, which are not capable of
      developing this protective regulatory mechanism by themselves.

PMID- 10924054
TI  - Effects of aging on single cardiac myocyte function in Fischer 344 x Brown Norway
      rats.
AB  - The Fischer 344 x Brown Norway (F344xBN) rat has been demonstrated to have a
      lower incidence of age-related pathology than other rat strains. Therefore, to
      elucidate the effects of aging on cardiac function, uncomplicated by compensatory
      effects caused by age-related pathology, cardiac myocytes were isolated from
      female F344xBN rats at 6 (young) and 32-33 (old) mo of age. Myocytes showed an
      increase in the relative amount of beta-myosin heavy chain with advanced age and
      a significant rightward shift in the tension-pCa curve from 5.78 +/- 0.02 pCa
      units in young adult myocytes to 5.66 +/- 0.03 pCa units. Consistent with a shift
      to a slower myosin isoform, the time from stimulation to peak sarcomere
      shortening increased with age from 50.5 +/- 1.3 to 58.9 +/- 1.0 ms. In contrast,
      no age-related difference was found in either the relengthening parameters or the
      Ca(2+) transient, indicating that relaxation is not directly altered by aging.
      This latter finding is at variance with previous studies in rat strains with
      higher rates of pathology. We conclude, therefore, that the primary effect of
      aging in isolated cardiac myocytes from the F344xBN rat model is a shift in the
      myosin heavy chain isoform. Changes in relaxation seen in other rat strains may
      result from compensatory mechanisms induced by pathological conditions.

PMID- 10924055
TI  - Interleukin-1beta, Src- and non-Src tyrosine kinases, and nitric oxide synthase
      induction in rat aorta in vitro.
AB  - We studied the potential roles for endogenous interleukin-1beta (IL-1beta) and
      for several signaling pathways in the spontaneous induction in vitro of inducible
      nitric oxide synthase (iNOS) in endothelium-denuded rat aorta rings. Added IL
      1beta augmented, whereas the IL-1beta receptor antagonist IL-1ra blocked,
      spontaneous iNOS induction. Furthermore, increases in IL-1beta mRNA preceded
      those of iNOS mRNA. Mitogen-activated protein kinase kinase and phosphatidyl
      inositol 3' kinase inhibition did not block iNOS induction, whereas nuclear
      factor kappaB inhibition did. The sarcoma virus tyrosine kinase (Src) family
      selective inhibitor 4-amino-5(4-methylphenyl)-7-(t-butyl)pyrazolo[3,4
      d]pyrimidine (PP1) blocked the upregulation of IL-1beta mRNA and the subsequent
      induction of iNOS but not the induction of iNOS stimulated by exogenously added
      IL-1beta. In contrast, the non-Src inhibitors TP 47/AG 213 and genistein and the
      tyrosine phosphatase inhibitor vanadate did not affect the spontaneous
      upregulation of IL-1beta mRNA but blocked both the IL-1beta-mediated and
      spontaneous induction of iNOS. We conclude that 1) the upregulation of tissue IL
      1beta, via a signaling pathway involving a Src family kinase, plays a key role in
      rat vascular iNOS induction and 2) non-Src tyrosine kinases play roles downstream
      from IL-1beta for iNOS induction.

PMID- 10924056
TI  - P(i) inhibits the SR Ca(2+) pump and stimulates pump-mediated Ca(2+) leak in
      rabbit cardiac myocytes.
AB  - Measurements of sarcoplasmic reticulum (SR) Ca(2+) uptake were made from aliquots
      of dissociated permeabilized ventricular myocytes using fura 2. Equilibration
      with 10 mM oxalate ensured a reproducible exponential decline of [Ca(2+)] from
      600 nM to a steady state of 100-200 nM after addition of Ca(2+). In the presence
      of 5 microM ruthenium red, which blocks the ryanodine receptor, the time course
      of the decline of [Ca(2+)] can be modeled by a Ca(2+)-dependent uptake process
      and a fixed Ca(2+) leak. Partial inhibition of the Ca(2+) pump with 1 microM
      cyclopiazonic acid or 50 nM thapsigargin reduced the time constant for Ca(2+)
      uptake but did not affect the SR Ca(2+) leak. Addition of 10 mM inorganic
      phosphate (P(i)) decreased the rate of Ca(2+) accumulation by the SR and
      increased the Ca(2+) leak rate. This effect was reversed on addition of 10 mM
      phosphocreatine. 10 mM P(i) had no effect on Ca(2+) leak from the SR after
      complete inhibition of the Ca(2+) pump. In conclusion, P(i) decreases the Ca(2+)
      uptake capacity of cardiac SR via a decrease in pump rate and an increase in
      Ca(2+) pump-dependent Ca(2+) leak.

PMID- 10924057
TI  - Effects of forearm bier block with bretylium on the hemodynamic and metabolic
      responses to handgrip.
AB  - We tested the hypothesis that a reduction in sympathetic tone to exercising
      forearm muscle would increase blood flow, reduce muscle acidosis, and attenuate
      reflex responses. Subjects performed a progressive, four-stage rhythmic handgrip
      protocol before and after forearm bier block with bretylium as forearm blood flow
      (Doppler) and metabolic (venous effluent metabolite concentration and (31)P-NMR
      indexes) and autonomic reflex responses (heart rate, blood pressure, and
      sympathetic nerve traffic) were measured. Bretylium inhibits the release of
      norepinephrine at the neurovascular junction. Bier block increased blood flow as
      well as oxygen consumption in the exercising forearm (P < 0.03 and P < 0.02,
      respectively). However, despite this increase in flow, venous K(+) release and
      H(+) release were both increased during exercise (P < 0.002 for both indexes).
      Additionally, minimal muscle pH measured during the first minute of recovery with
      NMR was lower after bier block (6.41 +/- 0.08 vs. 6.20 +/- 0.06; P < 0.036,
      simple effects). Meanwhile, reflex effects were unaffected by the bretylium bier
      block. The results support the conclusion that sympathetic stimulation to muscle
      during exercise not only limits muscle blood flow but also appears to limit
      anaerobiosis and H(+) release, presumably through a preferential recruitment of
      oxidative fibers.

PMID- 10924058
TI  - Doppler echo evaluation of pulmonary venous-left atrial pressure gradients: human
      and numerical model studies.
AB  - The simplified Bernoulli equation relates fluid convective energy derived from
      flow velocities to a pressure gradient and is commonly used in clinical
      echocardiography to determine pressure differences across stenotic orifices. Its
      application to pulmonary venous flow has not been described in humans. Twelve
      patients undergoing cardiac surgery had simultaneous high-fidelity pulmonary
      venous and left atrial pressure measurements and pulmonary venous pulsed Doppler
      echocardiography performed. Convective gradients for the systolic (S), diastolic
      (D), and atrial reversal (AR) phases of pulmonary venous flow were determined
      using the simplified Bernoulli equation and correlated with measured actual
      pressure differences. A linear relationship was observed between the convective
      (y) and actual (x) pressure differences for the S (y = 0.23x + 0.0074, r = 0.82)
      and D (y = 0.22x + 0.092, r = 0.81) waves, but not for the AR wave (y = 0. 030x +
      0.13, r = 0.10). Numerical modeling resulted in similar slopes for the S (y =
      0.200x - 0.127, r = 0.97), D (y = 0.247x - 0. 354, r = 0.99), and AR (y = 0.087x 
      0.083, r = 0.96) waves. Consistent with numerical modeling, the convective term
      strongly correlates with but significantly underestimates actual gradient because
      of large inertial forces.

PMID- 10924059
TI  - Matrix metalloproteinases and collagen ultrastructure in moderate myocardial
      ischemia and reperfusion in vivo.
AB  - Severe ischemic injury or infarction of myocardium may cause activation of matrix
      metalloproteinases (MMPs) and damage the interstitial matrix. However, it is
      unknown whether MMP activation and matrix damage occur after moderate ischemia
      and reperfusion that result in myocardial stunning without infarction, and if so
      whether such changes contribute to postischemic myocardial expansion and
      contractile dysfunction. To address these questions, open-chest anesthetized pigs
      underwent 90 min of regional ischemia (subendocardial blood flow 0.4 +/- 0.1 ml.
      g(-1). min(-1)) and 90 min of reperfusion. After ischemia plus reperfusion,
      histological and ultrastructural examination revealed no myocardial infarction or
      inflammatory cell infiltration. Myocardial MMP-9 content increased threefold with
      a fourfold increase in the active form (P < 0.001). Myocardial collagenase
      content doubled (P < 0.01) but remained in latent form. MMP-2 and tissue
      inhibitors of metalloproteinases were unaffected. Despite increases in MMPs,
      collagen ultrastructure (assessed by cell maceration scanning electron
      microscopy) was unaltered. Intracoronary administration of the MMP inhibitor GM
      2487 did not prevent or attenuate myocardial expansion (assessed by regional
      diastolic dimensions at near-zero left ventricular pressure) or contractile
      dysfunction. We conclude that although moderate ischemia and reperfusion alter
      myocardial MMP content and activity, these effects do not result in damage to
      interstitial collagen, nor do they contribute to myocardial expansion or
      contractile dysfunction.

PMID- 10924060
TI  - Gonadal hormones affect diameter of male rat cerebral arteries through
      endothelium-dependent mechanisms.
AB  - Gender is known to influence the incidence and severity of cerebrovascular
      disease. In the present study, luminal diameter was measured in vitro in
      pressurized middle cerebral artery segments from male rats that were either
      untreated, orchiectomized (ORX), ORX with testosterone treatment (ORX+TEST), or
      ORX with estrogen treatment (ORX+EST). The maximal passive diameters (0 Ca(2+) +
      3 mM EDTA) of arteries from all four groups were similar. In endothelium-intact
      arteries, myogenic tone was significantly greater in arteries from untreated and
      ORX+TEST compared with arteries from either ORX or ORX+EST. During exposure to
      N(G)-nitro-L-arginine-methyl ester (L-NAME), an NO synthase (NOS) inhibitor,
      myogenic tone significantly increased in all groups. The effect of L-NAME was
      significantly greater in arteries from untreated and ORX+EST compared with
      arteries from ORX and ORX+TEST rats. Differences in myogenic tone between ORX and
      ORX+TEST persisted after inhibition of NOS. After endothelium removal or
      inhibition of the cyclooxygenase pathway combined with K(+) channel blockers,
      myogenic tone differences between ORX and ORX+TEST were abolished. Wall thickness
      and forced dilation were not significantly different between arteries from ORX
      and ORX+TEST. Our data show that gonadal hormones affect myogenic tone in male
      rat cerebral arteries through NOS- and/or endothelium-dependent mechanisms.

PMID- 10924061
TI  - CD14-independent activation of cardiomyocyte signal transduction by bacterial
      endotoxin.
AB  - In the heart, lipopolysaccharide (LPS) induces the production of proinflammatory
      cytokines that cause myocardial dysfunction; however, the signaling pathways
      involved in cardiomyocyte responses are poorly understood. We studied LPS-induced
      signaling by treating cardiomyocyte cultures with 0.01-10 microgram/ml LPS for 0
      24 h in the presence or absence of 2.5% serum. Cytosolic and nuclear proteins
      were analyzed for expression and activation of protein kinases. Members of the
      extracellular signal-regulated kinase (ERK) and signal transducer and activators
      of transcription (STAT) protein families were uniformly expressed and
      specifically phosphorylated in response to LPS. Activation was biphasic; peaking
      at 5-10 min and 24 h after treatment. Inhibitor experiments provided evidence
      that ERK proteins may regulate STAT activity. Serum did not augment endotoxin
      induced phosphorylation. Although cardiomyocytes expressed low levels of CD14 and
      LPS-binding protein, specific enzymatic removal of glycosyl phosphatidylinositol
      linked receptors or incubation with an anti-CD14 antibody had no effect on kinase
      activation. Treatment of cells with an excess of detoxified LPS attenuated
      endotoxin-induced signaling. In addition, endotoxin stimulated specific binding
      of nuclear factors to AP-1, nuclear factor-kappaB (NF-kappaB), STAT1 (SIE, sis
      inducible element), and STAT3 consensus-binding sequences. Finally, inhibition of
      ERK phosphorylation reduced, and NF-kappaB nuclear translocation prevented, tumor
      necrosis factor-alpha production. Our results indicate that LPS-induced
      activation of signal transduction in cardiomyocytes occurs by a CD14-independent
      mechanism.

PMID- 10924063
TI  - Insulin resistance and the modulation of rat cardiac K(+) currents.
AB  - K(+) currents were measured using a whole cell voltage-clamp method in
      enzymatically isolated rat ventricular myocytes obtained from two
      hyperinsulinemic, insulin-resistant models. Fructose-fed rats as well as
      genetically obese rats, both of which are resistant to the metabolic effects of
      insulin, were used. The normal augmentation of a calcium-independent sustained
      K(+) current was reduced or abolished in insulin-resistant states. This
      resistance can be reversed by the insulin-sensitizing drug metformin. Vanadyl
      sulfate (3-4 wk treatment or after 5-6 h in vitro) enhanced the sustained K(+)
      current. The in vitro effect of vanadyl was blocked by cycloheximide. Insulin
      resistance of the K(+) current was not reversed by vanadyl sulfate. The results
      show that insulin resistance is expressed in terms of insulin actions on ion
      channels, in addition to its actions on metabolism. This resistance can be
      reversed by the insulin-sensitizing drug metformin. Vanadate compounds, which
      mimic the effects of insulin on metabolism, also mimic the augmenting effects of
      insulin on a cardiac K(+) current in a manner suggesting synthesis of new
      channels.

PMID- 10924062
TI  - Hypotonic stress-induced dual Ca(2+) responses in bovine aortic endothelial
      cells.
AB  - We have investigated the effects of hypotonic stress on intracellular calcium
      concentration ([Ca(2+)](i)) in bovine aortic endothelial cells. Reducing
      extracellular osmolarity by 5% to 40% elicited a steep Ca(2+) transient both in
      normal Krebs and Ca(2+)-free solutions. The hypotonic stress-induced Ca(2+)
      transient was inhibited by phospholipase C inhibitors (neomycin and U-73122), a
      P(2)-receptor antagonist (suramin), and an ATP-hydrolyzing enzyme (apyrase),
      suggesting that the hypotonic stress-induced Ca(2+) transient is mediated by ATP.
      A luciferin-luciferase assay confirmed that 40% hypotonic stress released 91.0
      amol/cell of ATP in 10 min. When the hypotonic stress-induced fast Ca(2+)
      transient was inhibited by neomycin, suramin, or apyrase, a gradual [Ca(2+)](i)
      increase was observed instead. This hypotonic stress-induced gradual [Ca(2+)](i)
      increase was inhibited by a phospholipase A(2) inhibitor, 4-bromophenacyl
      bromide. Furthermore, exogenously applied arachidonic acid induced a gradual
      [Ca(2+)](i) increase with an ED(50) of 13.3 microM. These observations indicate
      that hypotonic stress induces a dual Ca(2+) response in bovine aortic endothelial
      cells, i.e., an ATP-mediated fast Ca(2+) transient and an arachidonic acid
      mediated gradual Ca(2+) increase, the former being the predominant response in
      normal conditions.

PMID- 10924064
TI  - Adenosine A(2A) and A(2B) receptors in cultured human and porcine coronary artery
      endothelial cells.
AB  - We investigated the role of the cAMP link to the signal transduction mechanism
      coupled with adenosine A(2A) and A(2B) receptors in cultured human coronary
      artery endothelial cells (HCAEC) and porcine coronary artery endothelial cells
      (PCAEC). 2-[4-[2-?2-[(4-aminophenyl)methylcarbonylamino]ethylaminocarbon yl?eth
      yl]phenyl]ethylamino-5'- ethylcarboxamidoadenosine ((125)I-PAPA-APEC) (PAPA-APEC)
      was used to demonstrate the specific binding in PCAEC membranes. The specific
      binding was saturable and reversible with a maximal number of binding sites
      (B(max)) of 240 fmol/mg protein, and scatchard analysis revealed a single class
      of binding site with an equilibrium dissociation constant (K(d)) of 1. 17 +/-
      0.035 nM. In competition experiments, adenosine receptor agonists showed the
      following order of potency (based on IC(50)): 5'-(N-ethylcarboxamido)adenosine
      (NECA) >/= CGS-21680 > 2-chloroadenosine. This order appears to be consistent
      with the A(2) adenosine receptor classification. We also studied the effects of
      adenosine agonists on the accumulation of cAMP as an indirect approach to show
      the presence of functional A(2) receptors. Similarly, the same adenosine agonists
      (10(-7)-10(-4) M) elicited the production of cAMP in intact endothelial cells in
      a dose-dependent manner, exhibiting consistently with the A(2) adenosine receptor
      classification. A selective A(2A) adenosine receptor antagonist (ZM-241385, 10(
      8) M) significantly inhibited the effect of CGS-21680 on cAMP but only partly
      inhibited the effect of NECA, suggesting the presence of both A(2A) and A(2B)
      receptors. Western blot analysis further showed the immunoreactivity of A(2A) and
      A(2B) receptor at 45 and 36 kDa, respectively, in both HCAEC and PCAEC. Direct
      evidence for the presence of A(2A) and A(2B) receptors in cultured HCAEC and
      PCAEC by reverse transcription-polymerase chain reaction (RT-PCR), revealed
      expected PCR product sizes (205 and 173 bp) for A(2A) and A(2B) receptors in
      HCAEC and PCAEC, respectively. The data show that adenylate cyclase-coupled
      adenosine A(2A) and A(2B) receptors are present in coronary endothelial cells.

PMID- 10924065
TI  - Estimating oxygen transport resistance of the microvascular wall.
AB  - The problem of diffusion of O(2) across the endothelial surface in precapillary
      vessels and its utilization in the vascular wall remains unresolved. To establish
      a relationship between precapillary release of O(2) and vascular wall
      consumption, we estimated the intravascular flux of O(2) on the basis of
      published in vivo measurements. To interpret the data, we utilized a diffusion
      model of the vascular wall and computed possible physiological ranges for O(2)
      consumption. We found that many flux values were not consistent with the
      diffusion model. We estimated the mitochondrial-based maximum O(2) consumption of
      the vascular wall (M(mt)) and a possible contribution to O(2) consumption of
      nitric oxide production by endothelial cells (M(NO)). Many values of O(2)
      consumption predicted from the diffusion model exceeded M(mt) + M(NO). In
      contrast, reported values of O(2) consumption for endothelial and smooth muscle
      cell suspensions and vascular strips in vitro do not exceed M(mt). We conjecture
      that most of the reported values of intravascular O(2) flux are overestimated,
      and the likely source is in the experimental estimates of convective O(2)
      transport at upstream and downstream points of unbranched vascular segments.

PMID- 10924066
TI  - Heme oxygenase-1 is upregulated in the rat heart in response to chronic
      administration of angiotensin II.
AB  - Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into
      biliverdin, iron, and carbon monoxide. HO-1, an inducible form of HO, is thought
      to act as an endogenous antioxidant defense mechanism. To determine whether
      chronic administration of angiotensin II affects HO-1 expression in the heart,
      expression and localization of HO-1 were investigated in the heart of rats
      receiving angiotensin II infusion (0.7 mg. kg(-1). day(-1)) via osmotic minipump
      for up to 7 days. Angiotensin II induced formation of granulation tissue,
      characterized by myofibroblast proliferation, fibrous deposition, and
      inflammatory cell migration. Angiotensin II also upregulated cardiac HO-1
      expression. Immunohistochemistry revealed that HO-1 was intensively expressed in
      the granulation tissue. The selective AT(1)-receptor antagonist, losartan,
      completely, but hydralazine only partially, suppressed angiotensin II-induced
      granulation tissue formation and HO-1 upregulation. Chronic norepinephrine
      infusion (2.8 mg. kg(-1). day(-1)) did not induce granulation tissue formation or
      HO-1 upregulation. Our data suggest that angiotensin II upregulates cardiac HO-1
      expression in the newly formed inflammatory lesion, which may represent an
      adaptive response to angiotensin II-induced cardiac damage.

PMID- 10924067
TI  - Ouabain augments Ca(2+) transients in arterial smooth muscle without raising
      cytosolic Na(+).
AB  - Ouabain and other cardiotonic steroids (CTS) inhibit Na(+) pumps and are widely
      believed to exert their cardiovascular effects by raising the cytosolic Na(+)
      concentration ([Na(+)](cyt)) and Ca(2+). This view has not been rigorously
      reexamined despite evidence that low-dose CTS may act without elevating
      [Na(+)](cyt); also, it does not explain the presence of multiple, functionally
      distinct isoforms of the Na(+) pump in many cells. We investigated the effects of
      Na(+) pump inhibition on [Na(+)](cyt) (with Na(+) binding benzofuran
      isophthalate) and Ca(2+) transients (with fura 2) in primary cultured arterial
      myocytes. Low concentrations of ouabain (3-100 nM) or human ouabain-like compound
      or reduced extracellular K(+) augmented hormone-evoked mobilization of stored
      Ca(2+) but did not increase bulk [Na(+)](cyt). Augmentation depended directly on
      external Na(+), but not external Ca(2+), and was inhibited by 10 mM Mg(2+) or 10
      microM La(3+). Evoked Ca(2+) transients in pressurized small resistance arteries
      were also augmented by nanomolar ouabain and inhibited by Mg(2+). These results
      suggest that Na(+) enters a tiny cytosolic space between the plasmalemma (PL) and
      the adjacent sarcoplasmic reticulum (SR) via an Mg(2+)- and La(3+)-blockable
      mechanism that is activated by SR store depletion. The Na(+) and Ca(2+)
      concentrations within this space may be controlled by clusters of high ouabain
      affinity (alpha3) Na(+) pumps and Na/Ca exchangers located in PL microdomains
      overlying the SR. Inhibition of the alpha3 pumps by low-dose ouabain should raise
      the local concentrations of Na(+) and Ca(2+) and augment hormone-evoked release
      of Ca(2+) from SR stores. Thus the clustering of small numbers of specific PL ion
      transporters adjacent to the SR can regulate global Ca(2+) signaling. This
      mechanism may affect vascular tone and blood flow and may also influence Ca(2+)
      signaling in many other types of cells.

PMID- 10924068
TI  - Inhibition by nickel of the L-type Ca channel in guinea pig ventricular myocytes
      and effect of internal cAMP.
AB  - The characteristics of nickel (Ni) block of L-type Ca current (I(Ca, L)) were
      studied in whole cell patch-clamped guinea pig cardiac myocytes at 37 degrees C
      in the absence and presence of 100 microM cAMP in the pipette solution. Ni block
      of peak I(Ca,L) had a dissociation constant (K(d)) of 0.33 +/- 0.03 mM in the
      absence of cAMP, whereas in the presence of cAMP, the K(d) was 0.53 +/- 0.05 mM
      (P = 0.006). Ni blocked Ca entry via Ca channels (measured as I(Ca, L) integral
      over 50 ms) with similar kinetics (K(d) of 0.35 +/- 0.03 mM in cAMP-free solution
      and 0.30 +/- 0.02 mM in solution with cAMP, P = not significant). Under both
      conditions, 5 mM Ni produced a maximal block that was complete for the first
      pulse after application. Ni block of I(Ca,L) was largely use independent. Ni (0.
      5 mM) induced a positive shift (4 to 6 mV) in the activation curve of I(Ca,L).
      The block of I(Ca,L) by 0.5 mM Ni was independent of prepulse membrane potential
      (over the range of -120 to -40 mV). Ni (0.5 mM) also induced a significant shift
      in I(Ca,L) inactivation: by 6 mV negative in cAMP-free solution and by 4 mV
      positive in cells dialyzed with 100 microM cAMP. These data suggest that, in
      addition to blocking channel conductance by binding to a site in the channel
      pore, Ni may bind to a second site that influences the voltage-dependent gating
      of the L-type Ca channel. They also suggest that Ca channel phosphorylation
      causes a conformational change that alters some effects of Ni. The results may be
      relevant to excitation-contraction coupling studies, which have employed internal
      cAMP dialysis, and where Ni has been used to block I(Ca,L) and Ca entry into
      cardiac cells.

PMID- 10924069
TI  - Pyruvate potentiates inotropic effects of isoproterenol and Ca(2+) in rabbit
      cardiac muscle preparations.
AB  - Catecholamines and elevated extracellular Ca(2+) concentration ([Ca(2+)](o))
      augment contractile force by increased Ca(2+) influx and subsequent increased
      sarcoplasmic reticulum (SR) Ca(2+) release. We tested the hypothesis that
      pyruvate potentiates Ca(2+) release and inotropic response to isoproterenol and
      elevated [Ca(2+)](o), since this might be of potential importance in a clinical
      setting to circumvent deleterious effects on energy demand during application of
      catecholamines. Therefore, we investigated isometrically contracting myocardial
      preparations from rabbit hearts at 37 degrees C, pH 7.4, and a stimulation
      frequency of 1 Hz. At a [Ca(2+)](o) of 1.25 mM, pyruvate (10 mM) alone increased
      developed force (F(dev)) from 1.89 +/- 0.42 to 3.62 +/- 0.62 (SE) mN/mm(2) (n =
      8, P < 0.05) and isoproterenol (10(-6) M) alone increased F(dev) from 2.06 +/- 0.
      55 to 25.11 +/- 2.1 mN/mm(2) (P < 0.05), whereas the combination of isoproterenol
      and pyruvate increased F(dev) overproportionally from 1.89 +/- 0.42 to 33.31 +/-
      3.18 mN/mm(2) (P < 0.05). In a separate series of experiments, we assessed SR
      Ca(2+) content by means of rapid cooling contractures and observed that, despite
      no further increase in F(dev) by increasing [Ca(2+)](o) from 8 to 16 mM, 10 mM
      pyruvate could still increase F(dev) from 26.4 +/- 6.8 to 29.7 +/- 7. 1 mN/mm(2)
      (P < 0.05, n = 9) as well as the Ca(2+) load of the SR. The results show that the
      positive inotropic effects of pyruvate potentiate the inotropic effects of
      isoproterenol or Ca(2+), because in the presence of pyruvate, Ca(2+) and
      isoproterenol induced larger increases in inotropy than can be calculated by mere
      addition of the individual effects.

PMID- 10924070
TI  - Differences in mechanisms of SR dysfunction in ischemic vs. idiopathic dilated
      cardiomyopathy.
AB  - We examined 1) contractile properties and the intracellular Ca(2+) concentration
      ([Ca(2+)](i)) transient in cardiac myocytes and 2) sarcoplasmic reticulum (SR)
      Ca(2+) uptake and release function in myocardium from patients with end-stage
      heart failure caused by ischemic (ICM) vs. idiopathic dilated cardiomyopathy
      (DCM). The amplitude of cell motion was decreased 43 +/- 6% in ICM and 68 +/- 7%
      in DCM compared with that in normal organ donors (DN). Time to peak of shortening
      was increased 43 +/- 15% in DCM, but not in ICM. Prolongation of the relaxation
      time was more predominant in ICM. In DCM the systolic [Ca(2+)](i) was decreased
      27 +/- 9% and diastolic [Ca(2+)](i) was increased 36 +/- 11%. In ICM the
      diastolic [Ca(2+)](i) was increased 59 +/- 12% but the systolic [Ca(2+)](i) was
      unchanged. A significant decrease of the ATP-dependent SR Ca(2+) uptake rate
      associated with the reduction of the SR Ca(2+)-ATPase protein level was found in
      ICM. In contrast, the significant decrease in SR Ca(2+) release rate was distinct
      in DCM. The large amount of Ca(2+) retained in the SR associated with a
      significant decrease in the maximum reaction velocity and increase in the
      Michaelis-Menten constant in the caffeine concentration-response curve suggests a
      fundamental abnormality in the SR Ca(2+) release channel gating property in DCM.
      We conclude that potentially important differences exist in the intracellular
      Ca(2+) homeostasis and excitation-contraction coupling in ICM vs. DCM. The SR
      Ca(2+) release dysfunction may play an important pathogenetic role in the
      abnormal Ca(2+) homeostasis in DCM, and the SR Ca(2+) uptake dysfunction may be
      responsible for the contractile dysfunction in ICM.

PMID- 10924071
TI  - Phorbol ester stimulates cyclooxygenase-2 expression and prostanoid production in
      cardiac myocytes.
AB  - Phorbol-12-myristate- 13-acetate (PMA) has been shown to induce hypertrophy of
      cardiac myocytes. The prostaglandin endoperoxide H synthase isoform 2
      (cyclooxygenase-2, COX-2) has been associated with enhanced growth and/or
      proliferation of several types of cells. Thus we studied whether PMA induces COX
      2 and prostanoid products PGE(2) and PGF(2alpha) in neonatal ventricular myocytes
      and whether endogenous COX-2 products participate in their growth. In addition,
      we examined whether PMA affects interleukin-1beta (IL-1beta) stimulation of COX-2
      and PGE(2) production. PMA (0.1 micromol/l) stimulated growth, as indicated by a
      1.6-fold increase in [(3)H]leucine incorporation. PMA increased COX-2 protein
      levels 2. 8-fold, PGE(2) 3.7-fold, and PGF(2alpha) 2.9-fold. Inhibition of either
      p38 kinase or protein kinase C (PKC) prevented PMA-stimulated COX-2. Inhibition
      of COX-2 with either indomethacin or NS-398 had no effect on PMA-stimulated
      [(3)H]leucine incorporation. Exogenous administration of PGF(2alpha), but not
      PGE(2), stimulated protein synthesis. Treatment with IL-1beta (5 ng/ml) increased
      COX-2 protein levels 42-fold, whereas cotreatment with IL-1beta and PMA
      stimulated COX-2 protein only 32-fold. IL-1beta did not affect control or PMA
      stimulated protein synthesis. These findings indicate that: 1) PMA, acting
      through PKC and p38 kinase, enhances COX-2 expression, but chronic treatment with
      PMA partially inhibits IL-1beta stimulation of COX-2; and 2) exogenous
      PGF(2alpha) is involved in neonatal ventricular myocyte growth but endogenous COX
      2 products are not.

PMID- 10924072
TI  - Does autonomic blockade reveal a potent contribution of nitric oxide to
      locomotion-induced vasodilation?
AB  - We sought to test the role of nitric oxide (NO) in governing skeletal muscle
      (iliac) vascular conductance during treadmill locomotion in dogs (n = 6; 3.2 and
      6.4 km/h at 0% grade, and 6.4 km/h at 10% grade). As seen previously, the
      increase in muscle vascular conductance accompanying treadmill locomotion was
      little influenced by NO synthase inhibition alone with N(omega)-nitro-L-arginine
      methyl ester (L-NAME, 10 mg/kg iv), but the absolute value of conductance
      achieved during locomotion was reduced. Such ambiguous results provide an unclear
      picture regarding the importance of NO during locomotion. However, muscle
      vasodilation is normally restrained by the sympathetic system during locomotion.
      Thus a significant contribution by NO to the increase in vascular conductance
      that accompanies locomotion could be masked by partial withdrawal of the
      competing influence of sympathetic vasoconstrictor nerve activity secondary to
      the rise in arterial pressure following systemic L-NAME administration. To test
      this possibility, we compared the rise in muscle vascular conductance before and
      after L-NAME treatment while ganglionic transmission was blocked by
      hexamethonium. Under these conditions, L-NAME significantly reduced both the rise
      in vascular conductance (by 32%, P < 0.001) and the absolute level of vascular
      conductance (by 30%, P < 0.001) achieved during locomotion with no effect on
      blood flow. Thus augmented NO production normally provides a significant drive to
      relax vascular smooth muscle in active skeletal muscle during locomotion.
      Potential deficits stemming from the absence of NO following L-NAME treatment are
      masked by less intense sympathetic restraint when autonomic function is intact.

PMID- 10924073
TI  - Phenotypic screening for heart rate variability in the mouse.
AB  - We developed a technology for heart rate (HR) variability (HRV) analysis in the
      mouse for characterization of HR dynamics, modulated by vagal and sympathetic
      activity. The mouse is the principal animal model for studying biological
      processes. Mouse strains are now available harboring gene mutations providing
      fundamental insights into molecular mechanisms underlying cardiac electrical
      diseases. Future progress depends on enhanced understanding of these fundamental
      mechanisms and the implementation of methods for the functional analysis of mouse
      cardiovascular physiology. By telemetric techniques, standard time and frequency
      domain measures of HRV were computed with and without autonomic blockade, and
      baroreflex sensitivity testing was performed. HR modulation in the high-frequency
      component is predominantly mediated by the parasympathetic nervous system,
      whereas the low-frequency component is under the influence of both the
      parasympathetic and sympathetic systems. The presented technology and protocol
      allow for assessment of autonomic regulation of the murine HR. Phenotypic
      screening for HR regulation in mice will further enhance the value of the mouse
      as a model of heritable electrophysiological human disease.

PMID- 10924074
TI  - p38 MAP kinase pathway regulates angiotensin II-induced contraction of rat
      vascular smooth muscle.
AB  - Angiotensin II (ANG II) is a multifunctional hormone that exerts potent
      vasoconstrictor and hypertrophic effects on vascular smooth muscle. Here, we
      demonstrate that the p38 mitogen-activated protein (MAP) kinase pathway is
      involved in ANG II-induced vascular contraction. Addition of ANG II to rat aortic
      smooth muscle cells (SMC) caused a rapid and transient increase of p38 activity
      through activation of the AT(1) receptor subtype. This response to ANG II was
      strongly attenuated by pretreating cells with antioxidants and diphenylene
      iodonium and was mimicked by exposure of cells to H(2)O(2). Stimulation of p38 by
      ANG II resulted in the enzymatic activation of MAP kinase-activated protein
      (MAPKAP) kinase-2 and the phosphorylation of heat shock protein 27 (HSP27) in
      aortic SMC. Pretreatment of cells with the specific p38 MAP kinase inhibitor SB
      203580 completely blocked the ANG II-dependent activation of MAPKAP kinase-2 and
      phosphorylation of HSP27. ANG II also caused a robust activation of MAPKAP kinase
      2 in the intact rat aorta. Incubation with SB-203580 significantly decreased the
      potency of ANG II to induce contraction of rat aortic rings and depressed the
      maximal hormone response. These results suggest that the p38 MAP kinase pathway
      selectively modulates the vasoconstrictor action of ANG II in vascular smooth
      muscle.

PMID- 10924075
TI  - A spontaneously active focus drives a model atrial sheet more easily than a model
      ventricular sheet.
AB  - Tachycardias can be produced when focal activity at ectopic locations in either
      the atria or the ventricles propagates into the surrounding quiescent myocardium.
      Isolated rabbit atrioventricular nodal cells were coupled by an electronic
      circuit to a real-time simulation of an array of cell models. We investigated the
      critical size of an automatic focus for the activation of two-dimensional arrays
      made up of either ventricular or atrial model cells. Over a range of coupling
      conductances for the arrays, the critical size of the focus cell group for
      successful propagation was smaller for activation of an atrial versus a
      ventricular array. Failure of activation of the arrays at smaller focus sizes was
      due to the inhibition of pacing of the nodal cells. At low levels of coupling
      conductance, the ventricular arrays required larger sizes of the focus due to
      failure of propagation even when the focus was spontaneously active. The major
      differences between activation of the atrial and ventricular arrays is due to the
      higher membrane resistance (lower inward rectifier current) of the atrial cells.

PMID- 10924076
TI  - Niacin protects the isolated heart from ischemia-reperfusion injury.
AB  - Nicotinic acid (niacin) has been shown to decrease myocyte injury. Because
      interventions that lower the cytosolic NADH/NAD(+) ratio improve glycolysis and
      limit infarct size, we hypothesized that 1) niacin, as a precursor of NAD(+),
      would lower the NADH/NAD(+) ratio, increase glycolysis, and limit ischemic injury
      and 2) these cardioprotective benefits of niacin would be limited in conditions
      that block lactate removal. Isolated rat hearts were perfused without (Ctl) or
      with 1 microM niacin (Nia) and subjected to 30 min of low-flow ischemia (10% of
      baseline flow, LF) and reperfusion. To examine the effects of limiting lactate
      efflux, experiments were performed with 1) Ctl and Nia groups subjected to zero
      flow ischemia and 2) the Nia group treated with the lactate-H(+) cotransport
      inhibitor alpha-cyano-4-hydroxycinnamate under LF conditions. Measured variables
      included ATP, pH, cardiac function, tissue lactate-to-pyruvate ratio (reflecting
      NADH/NAD(+)), lactate efflux rate, and creatine kinase release. The lactate-to
      pyruvate ratio was reduced by more than twofold in Nia-LF hearts during baseline
      and ischemic conditions (P < 0.001 and P < 0.01, respectively), with concurrent
      lower creatine kinase release than Ctl hearts (P < 0.05). Nia-LF hearts had
      significantly greater lactate release during ischemia (P < 0.05 vs. Ctl hearts)
      as well as higher functional recovery and a relative preservation of high-energy
      phosphates. Inhibiting lactate efflux with alpha-cyano-4-hydroxycinnamate and
      blocking lactate washout with zero flow negated some of the beneficial effects of
      niacin. During LF, niacin lowered the cytosolic redox state and increased lactate
      efflux, consistent with redox regulation of glycolysis. Niacin significantly
      improved functional and metabolic parameters under these conditions, providing
      additional rationale for use of niacin as a therapeutic agent in patients with
      ischemic heart disease.

PMID- 10924077
TI  - Exercise adaptation attenuates VEGF gene expression in human skeletal muscle.
AB  - Angiogenesis is a component of the multifactoral adaptation to exercise training,
      and vascular endothelial growth factor (VEGF) is involved in extracellular matrix
      changes and endothelial cell proliferation. However, there is limited evidence
      supporting the role of VEGF in the exercise training response. Thus we studied
      mRNA levels of VEGF, using quantitative Northern analysis, in untrained and
      trained human skeletal muscle at rest and after a single bout of exercise. Single
      leg knee-extension provided the acute exercise stimulus and the training
      modality. Four biopsies were collected from the vastus lateralis muscle at rest
      in the untrained and trained conditions before and after exercise. Training
      resulted in a 35% increase in muscle oxygen consumption and an 18% increase in
      number of capillaries per muscle fiber. At rest, VEGF/18S mRNA levels were
      similar before (0.38 +/- 0.04) and after (1.2 +/- 0.4) training. When muscle was
      untrained, acute exercise greatly elevated VEGF/18S mRNA levels (16.9 +/- 6.7).
      The VEGF/18S mRNA response to acute exercise in the trained state was markedly
      attenuated (5.4 +/- 1.3). These data support the concept that VEGF is involved in
      exercise-induced skeletal muscle angiogenesis and appears to be subject to a
      negative feedback mechanism as exercise adaptations occur.

PMID- 10924078
TI  - Cross-bridge kinetics in rat myocardium: effect of sarcomere length and calcium
      activation.
AB  - We tested the hypotheses that Ca(2+) concentration ([Ca(2+)]) and sarcomere
      length (SL) modulate force development via graded effects on cross-bridge
      kinetics in chemically permeabilized rat cardiac trabeculae. Using sinusoidal
      length perturbations, we derived the transfer functions of stiffness over a range
      of [Ca(2+)] at a constant SL of 2.1 micrometer (n = 8) and at SL of 2.0, 2.1, and
      2.2 micrometer (n = 4). We found that changes in SL affected only the magnitude
      of stiffness, whereas [Ca(2+)] affected the magnitude and phase-frequency
      relations. The data were fit to complex functions of two exponential processes.
      The characteristic frequencies (b and c) of these processes are indexes of cross
      bridge kinetics, with b relating to cross-bridge attachment to and c to
      detachment from certain non-force-generating states. Both were significantly
      affected by [Ca(2+)], with an increase in b and c of 140 and 44%, respectively,
      over the range of [Ca(2+)] studied (P < 0.01). In contrast, SL had no effect on
      the characteristic frequencies (P > 0.6). We conclude that Ca(2+) activation
      modulates force development in rat myocardium, at least in part, via a graded
      effect on cross-bridge kinetics, whereas SL effects are mediated mainly by
      recruitment of cross bridges.

PMID- 10924079
TI  - Role of superoxide in hemorrhagic shock-induced P-selectin expression.
AB  - Superoxide has been implicated in the regulation of endothelial cell adhesion
      molecule expression and the subsequent initiation of leukocyte-endothelial cell
      adhesion in different experimental models of inflammation. The objective of this
      study was to assess the contribution of oxygen radicals to P-selectin expression
      in a murine model of whole body ischemia-reperfusion, i.e., hemorrhage
      resuscitation (H/R), with the use of different strategies that interfere with
      either the production (allopurinol, CD11/CD18-deficient or p47(phox)-/- mice) or
      accumulation [intravenous superoxide dismutase (SOD), mutant mice that
      overexpress SOD] of oxygen radicals. P-selectin expression was quantified in
      different regional vascular beds by use of the dual-radiolabeled monoclonal
      antibody technique. H/R elicited a significant increase in P-selectin expression
      in all vascular beds. This response was blunted in SOD transgenic mice and in
      wild-type mice receiving either intravenous SOD or the xanthine oxidase inhibitor
      allopurinol. Mice genetically deficient in either a subunit of NADPH oxidase or
      the leukocyte adhesion molecule CD11/CD18 also exhibited a reduced P-selectin
      expression. These results implicate superoxide, derived from both xanthine
      oxidase and NADPH oxidase, as mediators of the increased P-selectin expression
      observed in different regional vascular beds exposed to hemorrhage and
      retransfusion.

PMID- 10924080
TI  - Altered E-C coupling in rat ventricular myocytes from failing hearts 6 wk after
      MI.
AB  - Excitation-contraction (E-C) coupling was investigated in rat hearts 6 wk after
      induction of myocardial infarction (MI) by ligation of the left coronary artery.
      Heart weight was increased by 74% and left ventricular end-diastolic pressure was
      23 +/- 2 mmHg in MI compared with 8 +/- 2 mmHg in sham-operated controls (Sham, P
      < 0.001). Cell shortening was measured in voltage-clamped myocytes at 36 degrees
      C. In solutions where Cs(+) had been replaced by K(+), the voltage dependence of
      contraction was sigmoidal between -20 and +100 mV in Sham and MI cells. Verapamil
      (20 microM) blocked L-type Ca(2+) current and reduced contraction in Sham cells
      by approximately 50% (P < 0.01) but did not decrease contraction significantly in
      MI cells at test potentials above +10 mV. Verapamil-insensitive contractions were
      blocked by Ni(2+) (5 mM). Na(+)/Ca(2+) exchange current was doubled in MI
      compared with Sham cells at test potentials between -20 and +80 mV (P < 0.05),
      whereas mRNA and protein expression increased by 30-40%. Finally, voltage
      dependence of contraction was bell shaped in Na(+)-free solutions, but
      contraction was significantly increased in MI cells over a wider voltage range (P
      < 0.05). The insensitivity to Ca(2+) channel block in MI cells may result from an
      increased contribution of the Na(+)/Ca(+) exchanger to triggering of E-C
      coupling. These results suggest significant changes in E-C coupling in the
      hypertrophy and failure that develop in response to extensive MI.

PMID- 10924081
TI  - Presynaptic beta(2)-adrenoceptors mediate nicotine-induced NOergic neurogenic
      dilation in porcine basilar arteries.
AB  - We previously reported that nicotine-induced nitric oxide (NO)-mediated cerebral
      neurogenic vasodilation was dependent on intact sympathetic innervation. We
      hypothesized that nicotine acted on sympathetic nerve terminals to release
      norepinephrine (NE), which then acted on adrenoceptors located on the neighboring
      nitric oxidergic (NOergic) nerve terminals to release NO, resulting in
      vasodilation. The adrenoceptor subtype in mediating nicotine-induced vasodilation
      in isolated porcine basilar arterial rings denuded of endothelium was therefore
      examined pharmacologically and immunohistochemically. Results from using an in
      vitro tissue bath technique indicated that propranolol and preferential beta(2)
      adrenoceptor antagonists (ICI-118,551 and butoxamine), in a concentration
      dependent manner, blocked the relaxation induced by nicotine (100 microM) without
      affecting the relaxation elicited by transmural nerve stimulation (TNS, 8 Hz). In
      contrast, preferential beta(1)-adrenoceptor antagonists (atenolol and CGP-20712A)
      did not affect either nicotine- or TNS-induced relaxation. Results of double
      labeling studies indicated that beta(2)-adrenoceptor immunoreactivities and NADPH
      diaphorase reactivities were colocalized in the same nerve fibers in basilar and
      middle cerebral arteries. These findings suggest that NE, which is released from
      sympathetic nerves upon application of nicotine, acts on presynaptic beta(2)
      adrenoceptors located on the NOergic nerve terminals to release NO, resulting in
      vasodilation. In addition, nicotine-induced relaxation was enhanced by yohimbine,
      an alpha(2)-adrenoceptor antagonist, which, however, did not affect the
      relaxation elicited by TNS. Prazosin, an alpha(1)-adrenoceptor antagonist, on the
      other hand, did not have any effect on relaxation induced by either nicotine or
      TNS. The predominant facilitatory effect of beta(2)-adrenoceptors in releasing NO
      may be compromised by presynaptic alpha(2)-adrenoceptors.

PMID- 10924082
TI  - Lack of hypoxic stimulation of VEGF secretion from neutrophils and platelets.
AB  - Low oxygen (O(2)) is the key stimulus for expression of vascular endothelial
      growth factor (VEGF) in several adherent cells. Whether hypoxia also directs the
      release of VEGF protein from neutrophils (polymorphonuclear neutrophils; PMN) and
      platelets has not been investigated. We therefore compared VEGF release of
      platelets, PMN, and human vascular smooth muscle cells (HSMC) in response to
      hypoxia with that to activators of cellular degranulation. In contrast to HSMC,
      VEGF release from PMN and platelets or VEGF mRNA expression in PMN was not
      stimulated under hypoxic conditions (1% O(2)). Hypo- or hyperthermia and
      acidosis, other conditions potentially associated with ischemic and inflammatory
      tissue injury, also did not stimulate VEGF secretion from PMN. However,
      stimulation of platelets with thrombin and of PMN with phorbol 12-myristate 13
      acetate induced a time-dependent release of VEGF, peaking after 30 and 60 min,
      respectively. This was blocked by the degranulation inhibitor pentoxifylline but
      not by the protein-synthesis inhibitor cycloheximide. We conclude that rapid
      release of VEGF from platelets and PMN may occur independently of oxygenation
      during inflammation and hemostasis.

PMID- 10924083
TI  - Frequency modulation within electrocardiograms during ventricular fibrillation.
AB  - Periods of reentrant activation and effective refractory periods are correlated
      with dominant frequency or reciprocal of cycle periods during ventricular
      fibrillation (VF). In the present study, we used an analysis technique based on
      Wigner transforms to quantify time-varying dominant frequencies in
      electrocardiograms (ECGs) during VF. We estimated dominant frequencies within
      orthogonal ECGs recorded in 10 dogs during trials of 10 s of VF and in 9 dogs
      during trials of 30 s of VF. In four additional dogs, we compared dominant
      frequencies during 10 s of VF before and after administration of amiodarone. Our
      results showed the following. 1) There was substantial frequency variation or
      modulation within the ECGs during 10 and 30 s of VF, the average variation being
      +/-15% from the mean frequency. Amiodarone decreased mean frequencies (P < 0.05)
      as expected; however, amiodarone also decreased the variation in frequencies (P <
      0.05). 2) During 30 s of VF, the dominant frequencies increased continuously from
      7.3 to 8.1 Hz (P < 0.05). The increase in frequency was almost linear with a rate
      of 0.022 Hz/s (r(2) = 0.93, P < 0.0005). 3) Modulation of frequencies during the
      first and the last one-half of 30 s of VF was not different. Average (in time)
      mean frequencies and modulation of frequencies were similar in all three ECGs. 4)
      Although the averages were similar, during any VF episode, dominant frequencies
      in ECGs recorded from different locations on the body surface were similar to
      each other at some times and markedly different from each other at other times.
      We conclude that during VF, 1) frequencies in ECGs vary considerably and
      continuously, and amiodarone decreases this variation; 2) mean frequencies
      increase linearly during first 30 s; 3) the variability in frequency does not
      change during 30 s; and 4) at any given time, the frequencies within spatially
      different body surface ECGs can be either similar or markedly different.

PMID- 10924084
TI  - Glucocorticoid pretreatment protects cardiac function and induces cardiac heat
      shock protein 72.
AB  - Acute administration of glucocortiocoids reduces inflammation. Increasing
      knowledge of the mechanisms of action indicate that pretreatment with
      glucocorticoids could have organ-protective effects. We investigated whether
      pretreatment with methylprednisolone (MP) protected the heart against ischemia
      reperfusion dysfunction, and we hypothetized that this protection might be due to
      induction of the cardioprotective heat shock protein 72 (HSP72). Rats were given
      vehicle or MP-40 mg/kg im as a double injection starting either 24 or 120 h (5
      days) before their hearts were excised for Langendorff perfusion (n = 6-11 hearts
      in each group). MP improved left ventricular function and coronary flow during
      reperfusion after 30 min of global ischemia and reduced infarct size. Cardiac
      HSP72 gradually increased in a 24-h time course after MP treatment, and the
      increase was sustained 5 days afterward (immunoblotting). HSP72 mRNA was either
      reduced or unchanged, indicating a posttranscriptional regulation. Pretreatment
      with hydrocortisone or dexamethasone (n = 7-8 hearts of each) similarily
      increased cardiac HSP72 24 h afterward. This paper demonstrates that
      glucocorticoids increase cardiac HSP72 and protect organ function against
      ischemia-reperfusion injury.

PMID- 10924085
TI  - Role of ET(A) receptors in the regulation of vascular reactivity in rats with
      congestive heart failure.
AB  - Endothelium-derived nitric oxide (NO) and endothelin (ET)-1 interact to regulate
      vascular tone. In congestive heart failure (CHF), the release and/or the activity
      of both factors is affected. We hypothesized that the increased ET-1 production
      associated with CHF may result in a reduced smooth muscle sensitivity to NO. The
      aim of this study was to evaluate the effects of a chronic treatment with the
      ET(A)-receptor (ET receptor A) antagonist LU-135252 (LU) on cerebrovascular
      reactivity to sodium nitroprusside (SNP) in the rat infarct model of CHF. Rats
      were subjected to coronary artery ligation and were treated for 4 wk with placebo
      (n = 24) or LU (50 mg. kg(-1). day(-1), n = 29). CHF was associated with a
      decreased (P < 0.05) efficacy of SNP to induce relaxation of isolated middle
      cerebral arteries. Furthermore, neither NO synthase inhibition with N(omega)
      nitro-L-arginine (L-NNA) nor endothelial denudation affected the efficacy of SNP.
      Thus the endothelium no longer influences smooth muscle sensitivity to SNP. LU
      treatment, however, normalized (P < 0.05) smooth muscle sensitivity to SNP.
      Sensitivity of ET-1-induced contraction was increased in CHF only in the presence
      of L-NNA, whereas contraction induced by ET(B) receptor (receptor B) stimulation
      was increased (P < 0.05) in endothelium-denuded vessels. LU treatment restored
      these changes in reactivity and revealed a significant endothelium-dependent
      ET(B)-mediated relaxation after NO synthase inhibition. In conclusion, CHF
      decreases and uncouples cerebrovascular smooth muscle sensitivity to SNP from
      endothelial regulation. The observation that chronic ET(A) blockade restored most
      of the changes associated with CHF suggests that activation of the ET-1 system
      importantly contributes to the alteration in vascular reactivity observed in
      experimental CHF.

PMID- 10924086
TI  - NO metabolites accumulate in erythrocytes in proportion to carbon dioxide and
      bicarbonate concentration.
AB  - It is not known whether the ratio between the concentrations of NO metabolites
      (NOx) in plasma (pNOx) and in erythrocytes (eNOx) is constant or correlates with
      chemical parameters of the blood. We measured pH, PO(2), and PCO(2) and
      calculated bicarbonate concentration in 19 blood samples from the aorta, coronary
      sinus, and leg veins of 7 dogs. Erythrocytes were then separated by
      centrifugation and lysed with distilled water, and the lysate was ultrafiltered
      with a molecular cutoff of 50 kDa to remove the hemoglobin. NOx were measured in
      plasma and in the ultrafiltrate. NOx concentration was higher in erythrocytes,
      with eNOx/pNOx ranging from 4.38 to 14.60. Linear and significant correlations
      were found between the natural logarithm of eNOx/pNOx and PCO(2) (r = 0.70, P <
      0.001) or bicarbonate concentration (r = 0.72, P < 0.001). These results
      demonstrate, for the first time, that plasma NOx cannot be considered as a
      constant fraction of the total NOx in blood but varies dramatically in proportion
      to the CO(2)/bicarbonate concentration. To prevent an underestimation of venous
      arterial difference of NOx across organs, NOx should be measured in whole blood.

PMID- 10924087
TI  - Determination of EETs using microbore liquid chromatography with fluorescence
      detection.
AB  - Epoxyeicosatrienoic acids (EETs) are cytochrome P-450 metabolites of arachidonic
      acid involved in the regulation of vascular tone. The method of microbore column
      high-performance liquid chromatography with fluorescence detection was developed
      to determine 14,15-EET, 11, 12-EET, and the mixture of 8,9-EET and 5,6-EET.
      Tridecanoic acid (TA) was used as an internal standard. EETs were reacted with 2
      (2, 3-naphthalimino)ethyl trifluoromethanesulfonate (NT) to form highly
      fluorescent derivatives. A C(18) microbore column and a water-acetonitrile mobile
      phase were used for separation. Samples were excited at 259 nm, and the
      fluorescence was detected at 395 nm. The overall recoveries were 88% for EETs and
      40% for TA. EETs were detected in concentrations as low as 2 pg (signal-to-noise
      ratio = 3). The method was used to determine the EET production from endothelial
      cells (ECs). Bradykinin and methacholine (10(-6) M) stimulated an increase in the
      production of EETs by ECs two- and fivefold, respectively. This sensitive method
      may be used for determination of EETs at low concentrations normally detected in
      complex biological samples.

PMID- 10924088
TI  - Fluorescent HPLC assay for 20-HETE and other P-450 metabolites of arachidonic
      acid.
AB  - This study describes a fluorescent HPLC assay for measuring 20
      hydroxyeicosatetraenoic acid (20-HETE) and other cytochrome P-450 metabolites of
      arachidonic acid in urine, tissue, and interstitial fluid. An internal standard,
      20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, was added to samples, and the lipids
      were extracted and labeled with 2-(2,3-naphthalimino)ethyl
      trifluoromethanesulfonate. P-450 metabolites were separated on a C18 reverse
      phase HPLC column. Coelution and gas chromatography-mass spectrometry studies
      confirmed the identity of the 20-HETE peak. The 20-HETE peak can be separated
      from those for dihydroxyeicosatrienoic acids, other HETEs, and
      epoxyeicosatrienoic acids. Known amounts of 20-HETE were used to generate a
      standard curve (range 1-10 ng, r(2) = 0.98). Recovery of 20-HETE from urine
      averaged 95%, and the intra-assay variation was <5%. Levels of 20-HETE were
      measured in 100 microliter of urine and renal interstitial fluid or 0.1 mg of
      renal tissue. The assay was evaluated by studying the effects of 1
      aminobenzotriazole (ABT) on the excretion of 20-HETE in rats. ABT reduced
      excretion of 20-HETE by >65% and inhibited the formation of 20-HETE by renal
      microsomes. The availability of this assay should facilitate work in this field.

PMID- 10924089
TI  - Cytotoxic T lymphocyte responses to human immunodeficiency virus: control and
      escape.
AB  - Effective preventive and therapeutic intervention in individuals exposed to or
      infected with human immunodeficiency virus (HIV) depends, in part, on a clear
      understanding of the interactions between the virus and those elements of the
      host immune response which control viral replication. Recent advances have
      provided compelling evidence that cytotoxic T lymphocytes (CTLs) constitute an
      essential component of protective antiretroviral immunity. Here, we review
      briefly the significance of this work in the context of previous studies, and
      outline the mechanisms through which HIV evades CTL activity.

PMID- 10924090
TI  - Increased blood volume and CD34(+)CD38(-) progenitor cell recovery using a novel
      umbilical cord blood collection system.
AB  - A major problem with the use of umbilical cord/placental blood (UCB) is the
      limited blood volume that can be collected from a single donor. In this study, we
      evaluated a novel system for the collection of UCB and analyzed the kinetics of
      output of hematopoietic stem cells in the collected blood. Sequential UCB
      fractions were collected from 48 placentas by gravity following common
      procedures. When UCB flow was ended, collection was continued using the device.
      Nucleated cell (NC) density in each fraction was evaluated and the expression of
      CD34, CD38 and other hematopoietic markers was assessed by flow cytometry. The
      total collected volume was 60.9 +/- 26.2 ml (mean +/- SD, range 17-141.5). The
      device yield (volume collected using the device/total volume) was 26.5 +/- 15.1%.
      No significant difference was observed in NC count in sequential fractions. A
      significant increase in CD34(+) cell content in sequential fractions and a 2.07
      +/- 1.18-fold increase in the percentage of CD34(+) cells in the last versus
      first fraction were observed. Furthermore, within the CD34(+) population, the
      percentage of CD38(-) pluripotent stem cells in the first fraction was 3.24 +/-
      1.39, while in the last fraction it raised to 34.43 +/- 22.62. Thus, at the end
      of a collection performed following current procedures, further blood rich in the
      most primitive progenitor cells can be recovered. Therefore, the optimization and
      standardization of collection procedures are required to obtain maximal recovery
      from each placenta and increase the percentage of UCB units suitable for clinical
      use.

PMID- 10924091
TI  - Evidence of peripheral blood-derived, plastic-adherent CD34(-/low) hematopoietic
      stem cell clones with mesenchymal stem cell characteristics.
AB  - The hematopoietic system of vertebrates can be completely reconstituted with
      hematopoietic stem cells derived from the bone marrow, fetal liver, or cord
      blood, or even from peripheral-blood-derived cells. A cellular marker to identify
      those cells is the proteoglycan CD34, although we have shown that the earliest
      identifiable hematopoietic stem cell is a CD34(-) fibroblast-like cell which can
      differentiate into CD34(+) hematopoietic precursors. Peripheral blood mononuclear
      cells were isolated from the heparinized blood of a dog and incubated in tissue
      culture in the presence of interleukin 6. After 10-14 days, an adherent layer of
      fibroblast-like cells had developed and cells were immortalized using the SV-40
      large T antigen. Cells were cloned and subcloned by measures of limiting
      dilution, and various fibroblast-like clones were established. These fibroblast
      like cells either do not express the CD34 antigen or express CD34 on a low level,
      although transcribing CD34. The CD34(-/low) cells express osteocalcin as a
      mesenchymal cell marker. The fibroblast-like cells eventually differentiate
      spontaneously in vitro into CD34(+) precursors and show colony formation. Prior
      to autologous stem cell transplantation, one clone of choice (IIIG7) was
      transfected with a retroviral construct containing the green-fluorescence protein
      (GFP). The recipient dog was totally irradiated with 300 cGy and received a stem
      cell transplant with GFP-containing, immortalized, fibroblast-like monoclonal
      autologous stem cells (0.5 x 10(8)/kg dog). No additional growth factors were
      applied. The peripheral blood counts recovered after 23 days (WBC >500; platelets
      >10,000). A peripheral blood smear showed some dim but definite, although timely,
      limited expression of the GFP protein in nucleated peripheral blood cells just
      five weeks after transplantation. A bone marrow biopsy showed GFP-positive cells
      in the marrow cavity predominantly as "bone-lining cells."

PMID- 10924092
TI  - Differential expression of bcl-2 homologs in human CD34(+) hematopoietic
      progenitor cells induced to differentiate into erythroid or granulocytic cells.
AB  - The Bcl-2 family of proteins has been shown to play a central role in the
      regulation of apoptosis. We have examined the expression of several Bcl-2
      homologs upon stimulation of CD34(+) human hematopoietic progenitor cells.
      CD34(+) cells were induced to differentiate into predominantly erythroid cells in
      the presence of erythropoietin (Epo) and stem cell factor (SCF), while the
      addition of G-CSF and SCF led to differentiation predominantly into granulocytic
      cells, as demonstrated by immunophenotyping and morphological examination of
      cultured cells. In Epo- and SCF-stimulated cells, we found a marked increase in
      the level of Bcl-x(L) protein expression and downregulation of Bax expression,
      apparent from day 4 and more pronounced on days 8 and 21. In contrast, Bcl-x(L)
      protein expression was downregulated in G-CSF- and SCF-stimulated cells compared
      with cells cultured in medium alone, whereas there was no sign of change in the
      level of Bax. Mcl-1 expression showed a biphasic expression pattern in both early
      erythropoiesis and early granulopoiesis, but with an inverse regulation. Thus,
      Mcl-1 levels initially decreased in granulocytic progenitor cells and increased
      in erythroid progenitor cells. Finally, Bcl-2 expression was significantly
      downregulated in both Epo and SCF and G-CSF- and SCF-stimulated cells. The role
      of the distinct upregulation of Bcl-x(L) in early erythroid differentiation was
      further examined by use of specific ribozymes against Bcl-x(L). Addition of Bcl
      x(L) ribozymes promoted a clear increase in cell death of Epo- and SCF-stimulated
      cells, while erythroid differentiation was not affected. In conclusion, we found
      a distinct regulation of several Bcl-2 family members in CD34(+) cells dependent
      on the cytokine stimulation given. The use of Bcl-x(L)-specific ribozymes
      suggested that Bcl-x(L) is important for survival but not for differentiation of
      erythroid progenitor cells.

PMID- 10924093
TI  - Long-term (>1 year) analyses of chimerism and tolerance in mixed allogeneic
      chimeric mice using normal mouse combinations.
AB  - We examined the induction of tolerance using pancreas allografts over the long
      term (>1 year) in mice for the human application of mixed allogeneic bone marrow
      transplantation (BMT). T cell-depleted BM cells (BMCs) of C57BL/6 (B6) and C3H/He
      (C3H) mice were transplanted at various ratios into lethally irradiated B6 mice.
      The percentages of C3H cells in the chimeric mice gradually decreased, finally
      declining to only a small percentage, except when the ratio of donor to recipient
      BMCs was 100:1. However, despite the marked decreases in C3H-type cells, all the
      pancreas allografts of C3H mice were accepted when more than 1% C3H cells were
      detected in the peripheral blood. To examine the relationships between
      percentages of transplanted donor cells and acceptance of pancreas allografts,
      various percentages of donor and recipient BMCs (5% to 30%) were transplanted. It
      was found that more than 10% donor cells were necessary for the pancreas
      allografts to be accepted. In vitro assays for mixed lymphocyte reaction and
      generation of cytotoxic T-lymphocytes revealed that spleen cells in chimeric mice
      accepting pancreas allografts are tolerant to both host-type and donor-type major
      histocompatibility complex (MHC) determinants, but show a vigorous responsiveness
      to third-party MHC determinants. Since donor-type hemopoietic stem cells (HSCs)
      were detected in the BM and the liver of the chimeric mice, donor-derived HSCs
      and donor-derived hematolymphoid cells are responsible for the induction of
      tolerance. It should be noted that the percentage of donor-type HSCs is higher in
      the liver (6.2%) than in the BM (0.9%).

PMID- 10924094
TI  - Mobilization kinetics of CD34(+) cells in association with modulation of CD44 and
      CD31 expression during continuous intravenous administration of G-CSF in normal
      donors.
AB  - The aim of the present study is to evaluate the kinetics of CD34(+) cells and
      investigate the potential modulation of CD44 and CD31 expression on CD34(+) cells
      during continuous i.v. administration of G-CSF, thus to elucidate the possible
      mechanism of peripheral blood progenitor cell (PBPC) mobilization. Fifteen
      healthy donors were enrolled in this study. G-CSF (10 microg/kg/day) was
      administered for four consecutive days through continuous 24-h i.v. infusion. For
      measurement of complete blood counts, CD34(+) cell levels and their expression of
      CD44 and CD31, PB sampling was performed immediately before the administration of
      G-CSF (steady-state) and after 4, 8, 24, 48, 72, 96, and 120 h of G-CSF
      administration. The percentage and absolute number of CD34(+) cells significantly
      increased at day 3 (0. 55 +/- 0.09%, 51.12 +/- 24.83 x 10(3)/ml) and day 4 (0.47
      +/- 0.09%, 46.66 +/- 24.93 x 10(3)/ml), compared to the steady-state level (0. 06
      +/- 0.09%, 2.03 +/- 5.69 x 10(3)/ml). At day 3 to day 5 following the onset of G
      CSF administration, a strong decrease of CD44 and CD31 expression was observed on
      mobilized CD34(+) cells compared to controls: the relative fluorescence intensity
      of CD44 and CD31 was, respectively, 50%-70% and 40%-90% lower than that of
      controls. We conclude that continuous i.v. administration of G-CSF apparently
      results in more rapid mobilization of CD34(+) cells, and downregulation of CD44
      and CD31 on CD34(+) cells is likely to be involved in the mobilization of PBPC
      after treatment with G-CSF.

PMID- 10924097
TI  - The molecular perspective: simian virus 40.

PMID- 10924095
TI  - Effect of angiotensin II on hematopoietic progenitor cell proliferation.
AB  - Angiotensin II (AII) induced the proliferation of hematopoietic progenitor cells
      (HPC) isolated from murine bone marrow or human cord blood. The formation of
      colonies with more than 50 cells increased approximately five-sevenfold in
      cultures of murine lineage-negative (Lin(-)) bone marrow cells both in the
      presence (day 10) and absence (day 13) of colony-stimulating factors (CSF). This
      could be blocked with addition of Losartan, an antagonist of AIITR1. The increase
      in proliferation of early hematopoietic progenitors (Lin(-)Sca l(+) cells) by AII
      was approximately threefold and occurred only in the presence of CSF, suggesting
      that AII may affect mesenchymal stromal cells to induce CSF production and might
      directly affect early HPC. These in vitro studies were replicated with human HPC
      isolated from cord blood. AII also accelerated the proliferation and formation of
      colony-forming units (CFU)-granulocyte/erythroid/macrophage/megakaryocyte and CFU
      granulocyte/macrophage colonies by CD34(+)CD38(-) enriched progenitors but only
      in the presence of CSF. Additional studies also indicated that AII can act to
      increase proliferation in suspension culture. Exposure of CD34(+) cells to AII in
      suspension culture, prior to placement in a semisolid medium with erythropoietin,
      increased the formation of colonies with more than 50 cells and erythroid
      progenitors approximately five- and 20-fold, respectively. Further, mRNA for the
      AT1a receptor was expressed by human bone marrow CD34(+)CD38(-) cells,
      CD34(+)CD38(-) cells, and lymphocytes, but not mature myeloid cells. Similarly,
      mRNA for the AT1a receptor was expressed on human stromal cell clones, offering
      further support to the hypothesis that AII acts partially through the mesenchymal
      compartment of the bone marrow. These data suggest that AII may be a factor which
      stimulates the proliferation of hematopoietic progenitors.

PMID- 10924096
TI  - Isolation and characterization of neural stem cells from the adult human
      olfactory bulb.
AB  - We have recently isolated stem cells deriving from the olfactory bulbs of adult
      patients undergoing particularly invasive neurosurgery. After improving our
      experimental conditions, we have now obtained neural stem cells according to
      clonal analysis. The cells can be expanded, established in continuous cell lines
      and differentiated into the three classical neuronal phenotypes (neurons,
      astrocytes, and oligodendrocytes). Also, after exposition to leukemia inhibitory
      factor, we are able to improve the number of neurons, an ideal biological source
      for transplantation in various neurodegenerative disorders.

PMID- 10924098
TI  - Kinetic scheme for intermolecular RNA cleavage by a ribozyme derived from
      hepatitis delta virus RNA.
AB  - A minimal kinetic mechanism for a trans-acting ribozyme derived from the HDV
      antigenomic RNA self-cleaving element was established from steady-state, pre
      steady-state, single-turnover, and binding kinetics. Rate constants for
      individual steps, including substrate binding and dissociation, cleavage, and
      product release and binding, were measured at 37 degrees C at pH 8.0 in 10 mM
      Mg(2+) using oligonucleotides as either substrates, noncleavable analogues or 3'
      product mimics. A substrate containing a normal 3',5'-linkage was cleaved with a
      first-order rate constant (k(2)) of 0.91 min(-)(1). The association rate constant
      for the substrate to the ribozyme (2.1 x 10(7) M(-)(1) min(-)(1)) was at the
      lower range of the expected value for RNA duplex formation, and the substrate
      dissociated with a rate constant (1.4 min(-)(1)) slightly faster than that for
      cleavage. Thus the binary complex was not at equilibrium with free enzyme and
      substrate prior to the cleavage step. Following cleavage, product release was
      kinetically ordered in that the 5' product was released rapidly (>12 min(-)(1))
      relative to the 3' product (6.0 x 10(-)(3) min(-)(1)). Rapid 5' product release
      and lack of a demonstrable binding site for the 5' product could contribute to
      the difficulty in establishing the ribozyme-catalyzed reverse reaction
      (ligation). Slow release of the 3' product was consistent with the extremely low
      turnover under steady-state conditions as 3' product dissociation was rate
      limiting. The equilibrium dissociation constant for the substrate was 24-fold
      higher than that of the 3' cleavage product. A substrate with a 2',5'-linkage at
      the cleavage site was cleaved with a rate constant (k(2)) of 1.1 x 10(-)(2) min(
      )(1). Thus, whereas cleavage of a 3',5'-linkage followed a Briggs-Haldane
      mechanism, 2', 5' cleavage followed a Michaelis-Menten mechanism.

PMID- 10924099
TI  - 5a-formylbicyclomycin: studies on the bicyclomycin-Rho interaction.
AB  - Bicyclomycin (1) is a commercial antibiotic whose primary site of action is the
      rho transcription termination factor. A new bicyclomycin irreversible
      inactivator, 5a-formylbicyclomycin (3), was prepared to provide information
      concerning the bicyclomycin-rho inactivation process and the drug's binding
      pocket within rho. The apparent I(50) value for 3 was 35 microM, showing that 3
      was a more effective inhibitor of rho poly C-dependent ATPase activity than 1
      (I(50) = 60 microM). Mechanistic studies demonstrated that 3 inhibited poly C
      dependent ATP hydrolysis, in part, by a reversible, noncompetitive pathway with
      respect to ATP (K(i) = 62 microM). Incubation of 3 with rho led to efficient
      imine formation. Adding excess 1 to solutions containing 3 and rho prevented
      imine formation, demonstrating that 1 and 3 bind to the same active site in the
      protein. The 3-rho imine was stabilized by either ATP or ADP or by both, and was
      converted to the nonreversible 3-rho amine adduct upon treatment with NaBH(4).
      Mass spectrometric analysis of the amine provided a stoichiometry of
      approximately five bound 3 per rho hexamer indicating the number of bicyclomycin
      binding sites for the rho hexamer is between five and six. Monomer exchange
      experiments using modified 3-rho amine and wild type rho demonstrated that no
      more than two modified subunits per rho hexamer are sufficient to halt poly C
      dependent rho ATPase activity.

PMID- 10924100
TI  - Rho transcription factor: symmetry and binding of bicyclomycin.
AB  - The antibiotic bicyclomycin inhibits rho-dependent termination processes by
      interfering with RNA translocation by preventing RNA binding at the translocation
      site or by uncoupling the translocation process from ATP hydrolysis. Previous
      studies have shown that bicyclomycin binds near the ATP hydrolysis pocket on rho.
      The hexameric structure of rho indicates that it is in a class of enzymes with
      strong sequence similarity to F(1)-ATP synthase. The bicyclomycin derivative 5a
      formylbicyclomycin, an inhibitor comparable to bicyclomycin, was previously shown
      to form a stable imine with rho and when reduced to the amine with NaBH(4) to
      singly label five of the six rho subunits. Lysine-336 was identified by mass
      spectrometric analysis of trypsin-digested fragments as the site of 5a
      formylbicyclomycin adduction. A model of rho was made by threading the rho
      sequence on the known crystal structure of the alpha and beta subunits of F(1)
      ATP synthase. The model, along with information concerning the extent and site of
      5a-formylbicyclomycin adduction, indicates an overall C6 symmetry for rho subunit
      organization. We propose that the sequence similarity between rho and F(1)-ATP
      synthase extends to a similar quaternary structure and an equivalent enzyme
      mechanism. The proposed mechanism of RNA translocation coupled with ATP
      hydrolysis changes the overall symmetry of rho from C6 to C6/C3.

PMID- 10924101
TI  - A mechanism for plus-strand transfer enhancement by the HIV-1 nucleocapsid
      protein during reverse transcription.
AB  - The HIV-1 nucleocapsid protein (NC) functions as a nucleic acid chaperone during
      the plus-strand transfer step in reverse transcription by facilitating annealing
      of the primer binding site (PBS) sequence in the short plus-strand strong-stop
      DNA fragment [(+) SSDNA] to a complementary site located near the 3' end of the
      minus-strand DNA [(-) PBS DNA]. To investigate the mechanism by which NC performs
      this function, we have prepared an 18-nucleotide (-) PBS DNA for nuclear magnetic
      resonance (NMR) based structural and NC binding studies. The (-) PBS DNA forms a
      stable hairpin (T(m) approximately 42 +/- 5 degrees C) that contains a five
      residue loop and a bulged thymine in a guanosine-cytosine-rich stem. Addition of
      substoichiometric amounts of NC results in significant broadening and reductions
      in NMR signal intensities of the Watson-Crick base-paired imino protons and a
      reduction by 20 degrees C in the upper temperature at which the imino proton
      signals are detectable, consistent with destabilization of the structure. The
      results suggest that inefficient annealing in the absence of NC may be due to the
      intrinsic stability of an internal (-) PBS DNA hairpin and that NC facilitates
      strand transfer by destabilizing the hairpin and exposing stem nucleotides for
      base pairing with the PBS sequence in (+) SSDNA.

PMID- 10924102
TI  - Asymmetric DNA binding by a homodimeric bHLH protein.
AB  - Protein-DNA interactions that lie outside of the core recognition sequence for
      the Drosophila bHLH transcription factor Deadpan (Dpn) were investigated using
      minor groove binding pyrrole-imidazole polyamides. Electrophoretic mobility shift
      assays and DNase I footprinting demonstrate that hairpin polyamides bound
      immediately upstream, but not immediately downstream of the Dpn homodimer
      selectively inhibit protein-DNA complex formation. Mutation of the Dpn consensus
      binding site from the asymmetric sequence 5'-CACGCG-3' to the palindromic
      sequence 5'-CACGTG-3' abolishes asymmetric inhibition. A Dpn mutant containing
      the unnatural amino acid norleucine in place of lysine at position 80 in the bHLH
      loop region is not inhibited by the polyamide, suggesting that the epsilon amino
      group at this position is responsible for DNA contacts outside the major groove.
      We conclude that the nonpalindromic Dpn recognition site imparts binding
      asymmetry by providing unique contacts to the basic region of each monomer in the
      bHLH homodimer.

PMID- 10924103
TI  - Structural analysis of a chimeric bacterial alpha-amylase. High-resolution
      analysis of native and ligand complexes.
AB  - Several chimeric alpha-amylases genes were constructed by an in vivo
      recombination technique from the Bacillus amyloliquefaciens and Bacillus
      licheniformis genes. One of the fusion amylases (hereafter BA2), consisting of
      residues 1-300 from B. amyloliquefaciens and 301-483 from B. licheniformis, has
      been extensively studied by X-ray crystallography at resolutions between 2.2 and
      1.7 A. The 3-dimensional structure of the native enzyme was solved by multiple
      isomorphous replacement, and refined at a resolution of 1.7 A. It consists of 483
      amino acids, organized similarly to the known B. lichiniformis alpha-amylase
      structure [Machius et al. (1995) J. Mol. Biol. 246, 545-559], but features 4
      bound calcium ions. Two of these form part of a linear cluster of three ions, the
      central ion being attributed to sodium. This cluster lies at the junction of the
      A and B domains with one calcium of the cluster structurally equivalent to the
      major Ca(2+) binding site of fungal alpha-amylases. The third calcium ion is
      found at the interface of the A and C domains. BA2 contains a fourth calcium
      site, not observed in the B. licheniformis alpha-amylase structure. It is found
      on the C domain where it bridges the two beta-sheets. Three acid residues
      (Glu261, Asp328, and Asp231) form an active site similar to that seen in other
      amylases. In the presence of TRIS buffer, a single molecule of TRIS occupies the 
      1 subsite of the enzyme where it is coordinated by the three active-center
      carboxylates. Kinetic data reveal that BA2 displays properties intermediate to
      those of its parents. Data for crystals soaked in maltooligosaccharides reveal
      the presence of a maltotriose binding site on the N-terminal face of the
      (beta/alpha)(8) barrel of the molecule, not previously described for any alpha
      amylase structure, the biological function of which is unclear. Data for a
      complex soaked with the tetrasaccharide inhibitor acarbose, at 1.9 A, reveal a
      decasaccharide moiety, spanning the -7 to +3 subsites of the enzyme. The
      unambiguous presence of three unsaturated rings in the (2)H(3) half-chair/(2)E
      envelope conformation, adjacent to three 6-deoxypyranose units, clearly
      demonstrates synthesis of this acarbose-derived decasaccharide by a two-step
      transglycosylation mechanism.

PMID- 10924104
TI  - Backbone dynamics of human Cu,Zn superoxide dismutase and of its monomeric
      F50E/G51E/E133Q mutant: the influence of dimerization on mobility and function.
AB  - The backbone assignment of reduced human dimeric Cu,Zn superoxide dismutase (SOD)
      was performed on a sample 100% enriched in (15)N, (13)C and 70% enriched in (2)H.
      (15)N T(1), T(2), and T(1)(rho) and (15)N-(1)H NOE assignment was performed at
      600 MHz proton frequency on both wild-type SOD and the monomeric F50E/G51E/E133Q
      mutant. This allowed a comparison of the mobility in the subnanosecond and in the
      millisecond to microsecond time scales of the two systems. Both proteins are
      rather rigid, although some breathing of the beta sheets is detected in the wild
      type dimer. The monomer displays large mobility in the loops in the first part of
      the sequence, in loop IVa where point mutations have been introduced and at the C
      terminus. The dimeric wild type is rigidified at loop IVa and at the C-terminus.
      Only loop VII shows a higher mobility in the dimer (besides some individual NH
      moieties). Conformational equilibria are displayed in the monomeric form around
      cysteines 57 and 146, thus explaining the disorder of arginine 143 which is the
      most important residue in guiding O(2)(-) toward the copper ion. The larger
      mobility in the wild type form with respect to the monomer in the picosecond to
      nanosecond time scale of helix alpha1 and loop VIIb, which provides the correct
      electrostatic driving force for O(2)(-) in the active channel, has been discussed
      in terms of favoring the activity of SOD.

PMID- 10924105
TI  - Dynamics of cellular retinoic acid binding protein I on multiple time scales with
      implications for ligand binding.
AB  - Cellular retinoic acid binding protein I (CRABPI) belongs to the family of
      intracellular lipid binding proteins (iLBPs), all of which bind a hydrophobic
      ligand within an internal cavity. The structures of several iLBPs reveal minimal
      structural differences between the apo (ligand-free) and holo (ligand-bound)
      forms, suggesting that dynamics must play an important role in the ligand
      recognition and binding processes. Here, a variety of nuclear magnetic resonance
      (NMR) spectroscopy methods were used to systematically study the dynamics of both
      apo and holo CRABPI at various time scales. Translational and rotational
      diffusion constant measurements were used to study the overall motions of the
      proteins. Both apo and holo forms of CRABPI tend to self-associate at high (1.2
      mM) concentrations, while at low concentrations (0.2 mM), they are predominantly
      monomeric. Rapid amide exchange rate and laboratory frame relaxation rate
      measurements at two spectrometer field strengths (500 and 600 MHz) were used to
      probe the internal motions of the individual residues. Several residues in the
      apo form, notably within the ligand recognition region, exhibit millisecond time
      scale motions that are significantly arrested in the holo form. In contrast, no
      significant differences in the high-frequency motions were observed between the
      two forms. These results provide direct experimental evidence for dynamics
      induced ligand recognition and binding at a specifically defined time scale. They
      also exemplify the importance of dynamics in providing a more comprehensive
      understanding of how a protein functions.

PMID- 10924106
TI  - Structural basis of DNA bridging by barrier-to-autointegration factor.
AB  - Barrier-to-autointegration factor (BAF) is a host cell protein that plays a
      crucial role in retroviral integration. Preintegration complexes (PICs) stripped
      of BAF lose their normal integration activity, which can be restored by
      incubation with purified BAF. BAF bridges double-stranded DNA both intra- and
      intermolecularly in a non-sequence-specific manner, leading to the formation of a
      nucleoprotein network. BAF also binds to the nuclear protein lamina-associated
      polypeptide 2 (LAP2), and is localized with chromatin during interphase and
      mitosis. The crystal structure of homodimeric human BAF has been determined to
      1.9 A resolution. The fold of the BAF monomer resembles that of the second domain
      of RuvA. This comparison revealed the presence of the helix-hairpin-helix (HhH)
      nonspecific DNA binding motif within BAF. A novel feature of BAF's HhH motif is
      the occupation of the metal binding site by the epsilon-amino group of Lys 6,
      providing an alternative means of sequestering positive charge. Mutational
      analysis corroborates the HhH motif's prominent role in DNA binding and argues
      against a previously proposed helix-turn-helix (HTH) binding site located in
      another region of the monomer. A model of BAF bridging DNA via the HhH motif is
      proposed.

PMID- 10924107
TI  - DNA phase transition promoted by replication initiator.
AB  - DNA is flexible and easily subjected to bending and wrapping via DNA/protein
      interaction. DNA supercoiling is known to play an important role in a variety of
      cellular events, such as transcription, replication, and recombination. It is,
      however, not well understood how the superhelical strain is efficiently
      redistributed during these reactions. Here we demonstrate a novel property of an
      initiator protein in DNA relaxation by utilizing a one-molecule-imaging
      technique, atomic force microscopy, combined with biochemical procedures. A
      replication initiator protein, RepE54 of bacterial mini-F plasmid (2.5 kb), binds
      to the specific sequences (iterons) within the replication region (ori2). When
      RepE54 binds to the iterons of the negatively supercoiled mini-F plasmid, it
      induces a dynamic structural transition of the plasmid to a relaxed state. This
      initiator-induced relaxation is mediated neither by the introduction of a DNA
      strand break nor by a local melting of the DNA double strand. Furthermore, RepE54
      is not wrapped by DNA repeatedly. These data indicate that a local strain imposed
      by initiator binding can induce a drastic shift of the DNA conformation from a
      supercoiled to a relaxed state.

PMID- 10924108
TI  - Solution structure of ZipA, a crucial component of Escherichia coli cell
      division.
AB  - ZipA, an essential component of cell division in Escherichia coli, interacts with
      the FtsZ protein at the midcell in one of the initial steps of septum formation.
      The high-resolution solution structure of the 144-residue C-terminal domain of E.
      coli ZipA (ZipA(185)(-)(328)) has been determined by multidimensional
      heteronuclear NMR. A total of 30 structures were calculated by means of hybrid
      distance geometry-simulated annealing using a total of 2758 experimental NMR
      restraints. The atomic root means square distribution about the mean coordinate
      positions for residues 6-142 for the 30 structures is 0.37 +/- 0.04 A for the
      backbone atoms, 0. 78 +/- 0.05 A for all atoms, and 0.45 +/- 0.04 A for all atoms
      excluding disordered side chains. The NMR solution structure of ZipA(185)(-)(328)
      is composed of three alpha-helices and a beta-sheet consisting of six
      antiparallel beta-strands where the alpha-helices and the beta-sheet form
      surfaces directly opposite each other. A C-terminal peptide from FtsZ has been
      shown to bind ZipA(185)(-)(328) in a hydrophobic channel formed by the beta-sheet
      providing insight into the ZipA-FtsZ interaction. An unexpected similarity
      between the ZipA(185)(-)(328) fold and the split beta-alpha-beta fold observed in
      many RNA binding proteins may further our understanding of the critical ZipA-FtsZ
      interaction.

PMID- 10924109
TI  - The yeast mitochondrial citrate transport protein: determination of secondary
      structure and solvent accessibility of transmembrane domain IV using site
      directed spin labeling.
AB  - To explore the spatial organization and functional dynamics of the citrate
      transport protein (CTP), a nitroxide scan was carried out along 22 consecutive
      residues within the fourth transmembrane domain (TMDIV). This domain has been
      implicated as being of unique importance to the CTP mechanism due to (i) the
      presence of two intramembranous positive charges that are essential for CTP
      function and (ii) the existence of a transmembrane aqueous surface within this
      domain which likely corresponds to a portion of the citrate translocation
      pathway. The sequence-specific variation in the mobilities of the introduced
      nitroxides and their accessibilities to molecular O(2) reveal an alpha-helical
      conformation along the sequence. The accessibilities to NiEDDA are out of phase
      with accessibilites to O(2), indicating that one face of the helix is solvated by
      the lipid bilayer while the other is solvated by an aqueous environment. A
      gradient of NiEDDA accessibility is observed along the helix surface facing the
      aqueous phase, and the EPR spectral line shapes at these sites indicate
      considerable motional restriction. In the context of the model where TMDIV lines
      the translocation pathway, these data suggest a barrier to passive diffusion
      through the pathway. This paper reports the first use of site-directed spin
      labeling to study mitochondrial transporter structure.

PMID- 10924110
TI  - Interruption of the internal water chain of cytochrome f impairs photosynthetic
      function.
AB  - The structure of cytochrome f includes an internal chain of five water molecules
      and six hydrogen-bonding side chains, which are conserved throughout the
      phylogenetic range of photosynthetic organisms from higher plants, algae, and
      cyanobacteria. The in vivo electron transfer capability of Chlamydomonas
      reinhardtii cytochrome f was impaired in site-directed mutants of the conserved
      Asn and Gln residues that form hydrogen bonds with water molecules of the
      internal chain [Ponamarev, M. V., and Cramer, W. A. (1998) Biochemistry 37, 17199
      17208]. The 251-residue extrinsic functional domain of C. reinhardtii cytochrome
      f was expressed in Escherichia coli without the 35 C-terminal residues of the
      intact cytochrome that contain the membrane anchor. Crystal structures were
      determined for the wild type and three "water chain" mutants (N168F, Q158L, and
      N153Q) having impaired photosynthetic and electron transfer function. The mutant
      cytochromes were produced, folded, and assembled heme at levels identical to that
      of the wild type in the E. coli expression system. N168F, which had a non
      photosynthetic phenotype and was thus most affected by mutational substitution,
      also had the greatest structural perturbation with two water molecules (W4 and
      W5) displaced from the internal chain. Q158L, the photosynthetic mutant with the
      largest impairment of in vivo electron transfer, had a more weakly bound water at
      one position (W1). N153Q, a less impaired photosynthetic mutant, had an internal
      water chain with positions and hydrogen bonds identical to those of the wild
      type. The structure data imply that the waters of the internal chain, in addition
      to the surrounding protein, have a significant role in cytochrome f function.

PMID- 10924111
TI  - Rhodococcus L-phenylalanine dehydrogenase: kinetics, mechanism, and structural
      basis for catalytic specificity.
AB  - Phenylalanine dehydrogenase catalyzes the reversible, pyridine nucleotide
      dependent oxidative deamination of L-phenylalanine to form phenylpyruvate and
      ammonia. We have characterized the steady-state kinetic behavior of the enzyme
      from Rhodococcus sp. M4 and determined the X-ray crystal structures of the
      recombinant enzyme in the complexes, E.NADH.L-phenylalanine and E.NAD(+). L-3
      phenyllactate, to 1.25 and 1.4 A resolution, respectively. Initial velocity,
      product inhibition, and dead-end inhibition studies indicate the kinetic
      mechanism is ordered, with NAD(+) binding prior to phenylalanine and the
      products' being released in the order of ammonia, phenylpyruvate, and NADH. The
      enzyme shows no activity with NADPH or other 2'-phosphorylated pyridine
      nucleotides but has broad activity with NADH analogues. Our initial structural
      analyses of the E.NAD(+).phenylpyruvate and E.NAD(+). 3-phenylpropionate
      complexes established that Lys78 and Asp118 function as the catalytic residues in
      the active site [Vanhooke et al. (1999) Biochemistry 38, 2326-2339]. We have
      studied the ionization behavior of these residues in steady-state turnover and
      use these findings in conjunction with the structural data described both here
      and in our first report to modify our previously proposed mechanism for the
      enzymatic reaction. The structural characterizations also illuminate the
      mechanism of the redox specificity that precludes alpha-amino acid dehydrogenases
      from functioning as alpha-hydroxy acid dehydrogenases.

PMID- 10924112
TI  - Differential coupling through Val-344 and Tyr-442 of trimethylamine dehydrogenase
      in electron transfer reactions with ferricenium ions and electron transferring
      flavoprotein.
AB  - Modeling studies of the trimethylamine dehydrogenase-electron transferring
      flavoprotein (TMADH-ETF) electron transfer complex have suggested potential roles
      for Val-344 and Tyr-442, found on the surface of TMADH, in electronic coupling
      between the 4Fe-4S center of TMADH and the FAD of ETF. The importance of these
      residues in electron transfer, both to ETF and to the artificial electron
      acceptor, ferricenium (Fc(+)), has been studied by site-directed mutagenesis and
      stopped-flow spectroscopy. Reduction of the 6-(S)-cysteinyl FMN in TMADH is not
      affected by mutation of either Tyr-442 or Val-344 to a variety of alternate side
      chains, although there are modest changes in the rate of internal electron
      transfer from the 6-(S)-cysteinyl FMN to the 4Fe-4S center. The kinetics of
      electron transfer from the 4Fe-4S center to Fc(+) are sensitive to mutations at
      position 344. The introduction of smaller side chains (Ala-344, Cys-344, and Gly
      344) leads to enhanced rates of electron transfer, and likely reflects shortened
      electron transfer "pathways" from the 4Fe-4S center to Fc(+). The introduction of
      larger side chains (Ile-344 and Tyr-344) reduces substantially the rate of
      electron transfer to Fc(+). Electron transfer to ETF is not affected, to any
      large extent, by mutation of Val-344. In contrast, mutation of Tyr-442 to Phe,
      Leu, Cys, and Gly leads to major reductions in the rate of electron transfer to
      ETF, but not to Fc(+). The data indicate that electron transfer to Fc(+) is via
      the shortest pathway from the 4Fe-4S center of TMADH to the surface of the
      enzyme. Val-344 is located at the end of this pathway at the bottom of a small
      groove on the surface of TMADH, and Fc(+) can penetrate this groove to facilitate
      good electronic coupling with the 4Fe-4S center. With ETF as an electron
      acceptor, the observed rate of electron transfer is substantially reduced on
      mutation of Tyr-442, but not Val-344. We conclude that the flavin of ETF does not
      penetrate fully the groove on the surface of TMADH, and that electron transfer
      from the 4Fe-4S center to ETF may involve a longer pathway involving Tyr-442.
      Mutation of Tyr-442 likely disrupts electron transfer by perturbing the
      interaction geometry of TMADH and ETF in the productive electron transfer
      complex, leading to less efficient coupling between the redox centers.

PMID- 10924113
TI  - Characterization of recombinant wild type and site-directed mutations of
      apolipoprotein C-III: lipid binding, displacement of ApoE, and inhibition of
      lipoprotein lipase.
AB  - The physicochemical properties of recombinant wild type and three site-directed
      mutants of apolipoprotein C-III (apoC-III), designed by molecular modeling to
      alter specific amino acid residues implicated in lipid binding (L9T/T20L,
      F64A/W65A) or LPL inhibition (K21A), were compared. Relative lipid binding
      efficiencies to dimyristoylphosphatidylcholine (DMPC) were L9T/T20L > WT >K21A >
      F64A/W65A with an inverse correlation with size of the discoidal complexes
      formed. Physicochemical analysis (Trp fluorescence, circular dichroism, and
      GdnHCl denaturation) suggests that L9T/T20L forms tighter and more stable lipid
      complexes with phospholipids, while F64A/W65A associates less tightly. Lipid
      displacement properties were tested by gel-filtrating
      apoE:dipalmitoylphosphatidylcholine (DPPC) discoidal complexes mixed with the
      various apoC-III variants. All apoC-III proteins bound to the apoE:DPPC
      complexes; the amount of apoE displaced from the complex was dependent on the
      apoC-III lipid binding affinity. All apoC-III proteins inhibited LPL in the
      presence or absence of apoC-II, with F64A/W65A displaying the most inhibition,
      suggesting that apoC-III inhibition of LPL is independent of lipid binding and
      therefore of apoC-II displacement. Taken together. these data suggest that the
      hydrophobic residues F64 and W65 are crucial for the lipid binding properties of
      apoC-III and that redistribution of the N-terminal helix of apoC-III (L9T/T20L)
      enhances the stability of the lipid-bound protein, while LPL inhibition by apoC
      III is likely to be due to protein:protein interactions.

PMID- 10924114
TI  - Protection of radical intermediates at the active site of adenosylcobalamin
      dependent methylmalonyl-CoA mutase.
AB  - Adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the
      interconversion of methylmalonyl-CoA and succinyl-CoA via radical intermediates
      generated by substrate-induced homolysis of the coenzyme carbon-cobalt bond. From
      the structure of methylmalonyl-CoA mutase it is evident that the deeply buried
      active site is completely shielded from solvent with only a few polar contacts
      made between the protein and the substrate. Site-directed mutants of amino acid
      His244, a residue close to the inferred site of radical chemistry, were
      engineered to investigate its role in catalysis. Two mutants, His244Ala and
      His244Gln, were characterized using kinetic and spectroscopic techniques. These
      results confirmed that His244 is not an essential residue. However, compared with
      that of the wild type, k(cat) was lowered by 10(2)- and 10(3)-fold for the
      His244Gln and His244Ala mutants, respectively, while the K(m) for succinyl-CoA
      was essentially unchanged in both cases. The primary kinetic tritium isotope
      effect (k(H)/k(T)) for the His244Gln mutant was 1.5 +/- 0.3, and tritium
      partitioning was now found to be dependent on the substrate used to initiate the
      reaction, indicating that the rearrangement of the substrate radical to the
      product radical was extremely slow. The His244Ala mutant underwent inactivation
      under aerobic conditions at a rate between 1 and 10% of the initial rate of
      turnover. The crystal structure of the His244Ala mutant, determined at 2.6 A
      resolution, indicated that the mutant enzyme is unaltered except for a cavity in
      the active site which is occupied by an ordered water molecule. Molecular oxygen
      reaching this cavity may lead directly to inactivation. These results indicate
      that His244 assists directly in the unusual carbon skeleton rearrangement and
      that alterations in this residue substantially lower the protection of reactive
      radical intermediates during catalysis.

PMID- 10924116
TI  - A structure-function study of a proton transport pathway in the gamma-class
      carbonic anhydrase from Methanosarcina thermophila.
AB  - Four glutamate residues in the prototypic gamma-class carbonic anhydrase from
      Methanosarcina thermophila (Cam) were characterized by site-directed mutagenesis
      and chemical rescue studies. Alanine substitution indicated that an external loop
      residue, Glu 84, and an internal active site residue, Glu 62, are both important
      for CO(2) hydration activity. Two other external loop residues, Glu 88 and Glu
      89, are less important for enzyme function. The two E84D and -H variants
      exhibited significant activity relative to wild-type activity in pH 7.5 MOPS
      buffer, suggesting that the original glutamate residue could be substituted with
      other ionizable residues with similar pK(a) values. The E84A, -C, -K, -Q, -S, and
      -Y variants exhibited large decreases in k(cat) values in pH 7.5 MOPS buffer, but
      only exhibited small changes in k(cat)/K(m). These same six variants were all
      chemically rescued by pH 7.5 imidazole buffer, with 23-46-fold increases in the
      apparent k(cat). These results are consistent with Glu 84 functioning as a proton
      shuttle residue. The E62D variant exhibited a 3-fold decrease in k(cat) and a 2
      fold decrease in k(cat)/K(m) relative to those of the wild type in pH 7.5 MOPS
      buffer, while other substitutions (E62A, -C, -H, -Q, -T, and -Y) resulted in much
      larger decreases in both k(cat) and k(cat)/K(m). Imidazole did not significantly
      increase the k(cat) values and slightly decreased the k(cat)/K(m) values of most
      of the Glu 62 variants. These results indicate a primary preference for a
      carboxylate group at position 62, and support a proposed catalytic role for
      residue Glu 62 in the CO(2) hydration step, but do not definitively establish its
      role in the proton transport step.

PMID- 10924115
TI  - A closer look at the active site of gamma-class carbonic anhydrases: high
      resolution crystallographic studies of the carbonic anhydrase from Methanosarcina
      thermophila.
AB  - The prototype of the gamma-class of carbonic anhydrase has been characterized
      from the methanogenic archaeon Methanosarcina thermophila. Previously reported
      kinetic studies of the gamma-class carbonic anhydrase are consistent with this
      enzyme having a reaction mechanism similar to that of the mammalian alpha-class
      carbonic anhydrase. However, the overall folds of these two enzymes are
      dissimilar, and apart from the zinc-coordinating histidines, the active site
      residues bear little resemblance to one another. The crystal structures of zinc
      containing and cobalt-substituted gamma-class carbonic anhydrases from M.
      thermophila are reported here between 1.46 and 1.95 A resolution in the unbound
      form and cocrystallized with either SO(4)(2)(-) or HCO(3)(-). Relative to the
      tetrahedral coordination geometry seen at the active site in the alpha-class of
      carbonic anhydrases, the active site of the gamma-class enzyme contains
      additional metal-bound water ligands, so the overall coordination geometry is
      trigonal bipyramidal for the zinc-containing enzyme and octahedral for the cobalt
      substituted enzyme. Ligands bound to the active site all make contacts with the
      side chain of Glu 62 in manners that suggest the side chain is likely protonated.
      In the uncomplexed zinc-containing enzyme, the side chains of Glu 62 and Glu 84
      appear to share a proton; additionally, Glu 84 exhibits multiple conformations.
      This suggests that Glu 84 may act as a proton shuttle, which is an important
      aspect of the reaction mechanism of alpha-class carbonic anhydrases. A
      hydrophobic pocket on the surface of the enzyme may participate in the trapping
      of CO(2) at the active site. On the basis of the coordination geometry at the
      active site, ligand binding modes, the behavior of the side chains of Glu 62 and
      Glu 84, and analogies to the well-characterized alpha-class of carbonic
      anhydrases, a more-defined reaction mechanism is proposed for the gamma-class of
      carbonic anhydrases.

PMID- 10924117
TI  - Formation of the cystine between cysteine 225 and cysteine 462 from
      ribonucleoside diphosphate reductase is kinetically competent.
AB  - Participation of the formation of the cystine between cysteine 225 and cysteine
      462 in the R1 protein to the enzymatic mechanism of aerobic ribonucleoside
      diphosphate reductase from Escherichia coli has been examined by use of rapid
      quenching and site-directed immunochemistry. Prereduced ribonucleotide reductase
      in the presence of ATP was mixed with CDP in a quench flow apparatus. The
      reaction was terminated with a solution of acetic acid and N-ethylmaleimide. The
      protein was precipitated and digested with chymotrypsin and the proteinase from
      Staphylococcus aureus strain V8 in the presence of N-ethylmaleimide to yield the
      peptide SS[S-(N-ethylsuccinimid-2-yl)cysteinyl]VLIE containing cysteine 225 and
      the mixed disulfide between the peptide SSCVLIE and the peptide IALCTL containing
      cysteine 462. These two peptides were retrieved together from the digest by
      immunoadsorption. The affinity-purified peptides were modified at their amino
      termini with the fluorescent reagent 6-aminoquinolyl-N-hydroxysuccimidyl
      carbamate and submitted to high-pressure liquid chromatography. The areas of the
      respective peaks of fluorescence corresponding to the S-(N-ethylsuccimidyl)
      peptide, and the mixed disulfide were used to determine the percentage of the
      cystine that had formed during each interval. The rate constant for the formation
      of the cystine following the association of free, fully reduced ribonucleotide
      reductase with the reactant CDP was 8 s(-)(1). Because only 50% of the active
      sites participated in this pre-steady-state reaction, the maximum steady-state
      rate consistent with the involvement of this cystine in the enzymatic reaction
      would be 4 s(-1). Since the turnover number of the enzyme under the same
      conditions in a steady state assay was only 1 s(-)(1), the formation of the
      cystine between these two cysteines is kinetically competent.

PMID- 10924118
TI  - Magnesium-adenosine diphosphate binding sites in wild-type creatine kinase and in
      mutants: role of aromatic residues probed by Raman and infrared spectroscopies.
AB  - Two distinct methods were used to investigate the role of Trp residues during Mg
      ADP binding to cytosolic creatine kinase (CK) from rabbit muscle: (1) Raman
      spectroscopy, which is very sensitive to the environment of aromatic side-chain
      residues, and (2) reaction-induced infrared difference spectroscopy (RIDS) and
      photolabile substrate (ADP[Et(PhNO(2))]), combined with site-directed mutagenesis
      on the four Trp residues of CK. Our Raman results indicated that the environment
      of Trp and of Tyr were not affected during Mg-ADP binding to CK. Analysis of RIDS
      of wild-type CK, inactive W227Y, and active W210,217,272Y mutants suggested that
      Trp227 was not involved in the stacking interactions. Results are consistent with
      Trp227 being essential to prevent water molecules from entering in the active
      site [as suggested by Gross, M., Furter-Graves, E. M., Wallimann, T.,
      Eppenberger, H. M., and Furter, R. (1994) Protein Sci. 3, 1058-1068] and that
      another Trp could in addition help to steer the nucleotide in the binding site,
      although it is not essential for the activity of CK. Raman and infrared spectra
      indicated that Mg-ADP binding does not involve large secondary structure changes.
      Only 3-4 residues absorbing in the amide I region are directly implicated in the
      Mg-ADP binding (corresponding to secondary structure changes less than 1%),
      suggesting that movement of protein domains due to Mg-nucleotide binding do not
      promote large secondary structure changes.

PMID- 10924119
TI  - Factors affecting the thermodynamic stability of small asymmetric internal loops
      in RNA.
AB  - Optical melting experiments were used to determine the thermodynamic parameters
      for oligoribonucleotides containing small asymmetric internal loops. The results
      show a broad range of thermodynamic stabilities, which depend on loop size,
      asymmetry, sequence, closing base pairs, and length of helix stems. Imino proton
      NMR experiments provide evidence for possible hydrogen bonding in GA and UU
      mismatches in some asymmetric loops. The stabilizing effects of GA, GG, and UU
      mismatches on the thermodynamic stability of internal loops vary depending on the
      size and asymmetry of the loop. The dependence of loop stability on Watson-Crick
      closing base pairs may be explained by an account of hydrogen bonds. Models are
      presented for approximating the free energy increments of 2 x 3 and 1 x 3
      internal loops.

PMID- 10924120
TI  - Oligomeric states of the HIV-1 integrase as measured by time-resolved
      fluorescence anisotropy.
AB  - Self-assembly properties of HIV-1 integrase were investigated by time-resolved
      fluorescence anisotropy using tryptophanyl residues as a probe. From simulation
      analyses, we show that suitable photon counting leads to an accurate
      determination of long rotational correlation times in the range of 20-80 ns,
      permitting the distinction of the monomer, dimer, and tetramer from higher
      oligomeric forms of integrase. The accuracy of correlation times higher than 100
      ns is too low to distinguish the octamer from other larger species. The
      oligomeric states of the widely used detergent-solubilized integrase were then
      studied in solution under varying parameters known to influence the activity. In
      the micromolar range, integrase exists as high-order multimers such as an octamer
      and/or aggregates and a well-defined tetramer, at 25 and 35 degrees C,
      respectively. However, integrase is monomeric at catalytically active
      concentrations (in the sub-micromolar range). Detergents (NP-40 and CHAPS) and
      divalent cation cofactors (Mg(2+) and Mn(2+)) have a clear dissociative effect on
      the high multimeric forms of integrase. In addition, we observed that Mg(2+) and
      Mn(2+) have different effects on both the oligomeric state and the conformation
      of the monomer. This could explain in part why these two metal cations are not
      equivalent in terms of catalytic activity in vitro. In contrast, addition of
      Zn(2+) stimulates dimerization. Interestingly, this role of Zn(2+) in the
      multimerization process was evident only in the presence of Mg(2+) which by
      itself does not induce oligomerization. Finally, it is highly suggested that the
      presence of detergent during the purification procedure plays a negative role in
      the proper self-assembly of integrase. Accordingly, the accompanying paper [Leh,
      H., et al. (2000) Biochemistry 39, 9285-9294] shows that a detergent-free
      integrase preparation has self-assembly and catalytic properties different from
      those of the detergent-solubilized enzyme.

PMID- 10924121
TI  - Determinants of Mg2+-dependent activities of recombinant human immunodeficiency
      virus type 1 integrase.
AB  - The relationship between Mg(2+)-dependent activity and the self-assembly state of
      HIV-1 integrase was investigated using different protein preparations. The first
      preparations, IN(CHAPS) and IN(dial), were purified in the presence of detergent,
      but in the case of IN(dial), the detergent was removed during a final dialysis.
      The third preparation, IN(zn), was purified without any detergent. The three
      preparations displayed comparable Mn(2+)-dependent activities. In contrast, the
      Mg(2+)-dependent activity that reflects a more realistic view of the
      physiological activity strongly depended on the preparation. IN(CHAPS) was not
      capable of using Mg(2+) as a cofactor, whereas IN(zn) was highly active under the
      same conditions. In the accompanying paper [Deprez, E., et al. (2000)
      Biochemistry 39, 9275-9284], we used time-resolved fluorescence anisotropy to
      demonstrate that IN(CHAPS) was monomeric at the concentration of enzymatic
      assays. Here, we show that IN(zn) was homogeneously tetrameric under similar
      conditions. Moreover, IN(dial) that exhibited an intermediary Mg(2+)-dependent
      activity existed in a monomer-multimer equilibrium. The level of Mg(2+)- but not
      Mn(2+)-dependent activity of IN(dial) was altered by addition of detergent which
      plays a detrimental role in the maintenance of the oligomeric organization. Our
      results indicate that the ability of integrase to use Mg(2+) as a cofactor is
      related to its self-assembly state in solution, whereas Mn(2+)-dependent activity
      is not. Finally, the oligomeric IN(zn) was capable of binding efficiently to DNA
      regardless of the cationic cofactor, whereas the monomeric IN(CHAPS) strictly
      required Mn(2+). Thus, we propose that a specific conformation of integrase is a
      prerequisite for its binding to DNA in the presence of Mg(2+).

PMID- 10924122
TI  - Redox properties of protein disulfide bond in oxidized thioredoxin and lysozyme:
      a pulse radiolysis study.
AB  - We have studied the one-electron reduction of oxidized Chlamydomonas reinhardtii
      thioredoxin and compared it to that of hen egg white lysozyme, using CO(2)(*) (-)
      free radicals as reductants. This comparison shows that the thioredoxin
      disulfide/thiol redox couple has different properties than that of lysozyme: the
      disulfide radical pK(a) is much lower (around 5 for small disulfides, 4.62 for
      lysozyme, <3 for thioredoxin). To get a better understanding of the modulation of
      the thioredoxin redox properties we have constructed the mutants W35A and D30A.
      Their reduction by pulse radiolysis indicates that W35 strongly controls both the
      disulfide radical acidity (the pK(a) in W35A is equal to ca. 4), and the thiol
      reactivity. Asp30 is also involved in the control of proton transfer to the
      disulfide free radical. In addition, its removal seems to increase the reduction
      potential of the thioredoxin thiyl/thiol couple. Overall, the reduction
      properties of thioredoxin confirm its nature as a unique reductant.

PMID- 10924123
TI  - P67-phox-mediated NADPH oxidase assembly: imaging of cytochrome b558 liposomes by
      atomic force microscopy.
AB  - NADPH oxidase activity depends on the assembly of the cytosolic activating
      factors, p67-phox, p47-phox, p40-phox, and Rac with cytochrome b(558). The
      transition from an inactive to an active oxidase complex induces the transfer of
      electrons from NADPH to oxygen through cytochrome b(558). The assembly of oxidase
      complex was studied in vitro after reconstitution in a heterologous cell-free
      assay by using true noncontact mode atomic force microscopy. Cytochrome b(558)
      was purified from neutrophils and Epstein-Barr virus-immortalized B lymphocytes
      and incorporated into liposomes. The effect of protein glycosylation on liposome
      size and oxidase activity was investigated. The liposomes containing the native
      hemoprotein purified from neutrophils had a diameter of 146 nm, whereas after
      deglycosylation, the diameter was reduced to 68 nm, although oxidase activity was
      similar in both cases. Native cytochrome b(558) was used after purification in
      reconstitution experiments to investigate the topography of NADPH oxidase once it
      was assembled. For the first time, atomic force microscopy illustrated
      conformational changes of cytochrome b(558) during the transition from the
      inactive to the active state of oxidase; height measurements allow the
      determination of a size of 4 nm for the assembled complex. In the processes that
      were studied, p67-phox displayed a critical function; it was shown to be involved
      in both assembly and activation of oxidase complex while p47-phox proceeded as a
      positive effector and increased the affinity of p67-phox with cytochrome b(558),
      and p40-phox stabilizes the resting state. The results suggest that although an
      oligomeric structure of oxidase machinery has not been demonstrated, allosteric
      regulation mechanisms may be proposed.

PMID- 10924124
TI  - Inhibition of unwinding of G-quadruplex structures by Sgs1 helicase in the
      presence of N,N'-bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic
      diimide, a G-quadruplex-interactive ligand.
AB  - N,N'-Bis[2-(1-piperidino)ethyl]-3,4,9,10-perylenetetracarboxylic diimide (PIPER),
      a perylene derivative, is a very potent and selective G-quadruplex DNA
      interactive agent. It has been shown to inhibit DNA polymerase and telomerase by
      stacking externally to the G-tetrads in the G-quadruplex structures. Recently, we
      have demonstrated that this small molecule greatly accelerates the assembly of G
      quadruplex structures in a cell-free system. In this report, we present data
      demonstrating that PIPER prevents the unwinding of G-quadruplex structures by
      yeast Sgs1 helicase. Sgs1 belongs to the RecQ DNA helicase family whose members
      include other G-quadruplex DNA unwinding helicases, such as human Bloom's
      syndrome and human Werner's syndrome helicases. PIPER specifically prevents the
      unwinding of G-quadruplex DNA but not duplex DNA by Sgs1. Competition experiments
      indicate that this inhibitory activity is due to the interaction of PIPER with G
      quadruplex structures rather than the helicase itself. These results combined
      with previous studies suggest a possible mechanism of action for these G
      quadruplex-interactive agents inside cells: they might induce G-quadruplex
      formation in G-rich regions on genomic DNA, stabilize these structures, and
      prevent them from being cleared by enzymes such as helicases. The G-quadruplex
      structures may, in turn, disrupt some critical cellular events such as DNA
      replication, transcription regulation, and telomere maintenance.

PMID- 10924125
TI  - Binding of distamycin A and netropsin to the 12mer DNA duplexes containing mixed
      AT.GC sequences with at most five or three successive AT base pairs.
AB  - Circular dichroism (CD), isothermal calorimetric titrations (ITC), and
      temperature-dependent UV spectroscopy were used to investigate binding of the
      minor groove-directed ligands distamycin A (Dst) and netropsin (Net) to the
      following duplexes: d(GTTAGTATTTGG). d(CCAAATACTAAC),
      d(GTTAGTATATGG).d(CCATATACTAAC), d(GTTAGTACTTGG). d(CCAAGTACTAAC), and
      d(GTTAGTAGTTGG).d(CCAACTACTAAC). Our results reveal that Dst binds within the
      minor grooves of these dodecamers that contain five-AT and/or four-AT.GC binding
      sites exclusively in a dimeric high-affinity 2:1 binding mode (K approximately
      10(16) M(-)(2)). By contrast, Net exhibits high-affinity binding only when it
      binds in a 1:1 mode (K(1) approximately 10(9) M(-)(1)) to the two duplexes that
      contain five-AT sites (5'-TATTT-3' and 5'-TATAT-3'). Its further binding to these
      two duplexes occurs in a low-affinity mode (K(2) approximately 10(6) M(-)(1)) and
      results in the formation of 2:1 Net-DNA complexes. To the other two duplexes that
      contain sequences with at most three AT consecutive base pairs Net binds in two
      distinctive low-affinity 1:1 binding modes (K(1) approximately 10(7) M(-)(1),
      K(2) approximately 10(6) M(-)(1)). Competition experiments (CD and ITC
      titrations) reveal that Dst entirely displaces Net from its 1:1 and 2:1 complexes
      with any of the four duplexes. We discuss and interpret our optical and
      calorimetric results in the context of the available structural information about
      the complexes between DNA and the sequence-specific minor groove binders Dst and
      Net.

PMID- 10924127
TI  - Membrane lipids have multiple effects on interfacial catalysis by a phosphatidic
      acid-preferring phospholipase A1 from bovine testis.
AB  - We previously purified a cytosolic phospholipase A1 that could catalyze the
      preferential hydrolysis of phosphatidic acid in mixed-micelle assays. Here we
      studied the enzyme's interactions with unilamellar lipid membranes and examined
      effects of the lipids on enzyme binding, stability, and catalysis. A major
      finding was that membrane lipids could influence the stability, activity, and
      specificity of the enzyme under conditions where enzyme binding to the membranes
      was likely to be saturated. Thus, the enzyme was unstable at 37 degrees C in the
      absence of membranes but bound to membranes that contained anionic
      phosphoglycerides and could be stabilized by these membranes in the presence of
      albumin. The overall activity of the bound enzyme toward membrane
      phosphoglycerides, assayed in the presence of albumin, increased when
      phosphatidylethanolamine was substituted for phosphatidylcholine. Furthermore,
      the enzyme's catalytic preference for phosphatidic acid increased when
      cholesterol and diacylglycerol were included in the membranes, sn-1-stearoyl-2
      arachidonoylphosphatidylethanolamine was substituted for sn-1-palmitoyl-2
      oleoylphosphatidylethanolamine, and the concentration of phosphatidic acid was
      increased from 0 to 10 mol % of the total membrane phosphoglycerides. Finally,
      changes in the relative contents of phosphatidylcholine and phosphatidylserine in
      the membranes influenced the enzyme's catalytic preference for different
      molecular species of phosphatidic acid. These results provide the first available
      information about the enzyme's ability to interact with membranes and identify
      conditions that yield high enzyme activity toward membrane-associated
      phosphatidic acid.

PMID- 10924128
TI  - Inhibition of actin-myosin subfragment 1 ATPase activity by troponin I and IC:
      relationship to the thin filament states of muscle.
AB  - Troponin I (TnI) is the component of the troponin complex that inhibits
      actomyosin ATPase activity, and Ca(2+) binding to the troponin C (TnC) component
      reverses the inhibition. Effects of the binding of TnI and the TnI-TnC (TnIC)
      complex to actin-tropomyosin (actinTm) on ATPase and on the binding kinetics of
      myosin subfragment 1 (S1) were studied to clarify the mechanism of the
      inhibition. TnI and TnIC in the absence of Ca(2+) bind to actinTm and inhibit
      ATPase to similar levels with a stoichiometry of one TnI or one TnIC per one Tm
      and seven actin subunits. TnI also binds to actinTmTn in the presence of Ca(2+)
      with a stoichiometry and inhibition constant similar to those for the binding to
      actinTm of TnI and Tn in the absence of Ca(2+). Thus, in the presence of Ca(2+),
      the intrinsic TnI which is released from its binding site on actinTm does not
      interfere with the binding of an extra molecule of TnI to actinTmTn. The rate of
      S1 binding to actinTmTnI and to actinTmTnTnI in the presence of Ca(2+) was
      inhibited to the same extent as upon removal of Ca(2+) from actinTmTn. These
      studies show that TnI inhibits ATPase by the same mechanism as Tn in the absence
      of Ca(2+), by shifting the thin filament equilibria from the open state to the
      closed and blocked states.

PMID- 10924126
TI  - Novel function of human RLIP76: ATP-dependent transport of glutathione conjugates
      and doxorubicin.
AB  - Active transport of conjugated and unconjugated electrophiles out of cells is
      essential for cellular homeostasis. We have previously identified in human
      tissues a transporter, DNP-SG [S-(2, 4-dinitrophenyl)glutathione] ATPase, capable
      of carrying out this function [Awasthi et al. (1998) Biochemistry 37, 5231-5238,
      5239-5248]. We now report the cloning of DNP-SG ATPase. The sequence of the cDNA
      clone was identical to that of human RLIP76, a known Ral-binding protein. RLIP76
      expressed in E. coli was purified by DNP-SG affinity chromatography. Purified
      recombinant RLIP76: (1) had ATPase activity stimulated by DNP-SG or doxorubicin
      (DOX), and the K(m) values of RLIP76 for ATP, DOX, and DNP-SG were similar to
      those reported for DNP-SG ATPase; (2) upon reconstitution with asolectin as well
      as with defined lipids, catalyzed ATP-dependent transport of DNP-SG and DOX with
      kinetic parameters similar to those of DNP-SG ATPase; (3) when transfected into
      K562 cells, resulted in increased resistance to DOX, and increased ATP-dependent
      transport of DNP-SG and DOX by inside-out membrane vesicles from transfected
      cells; (4) direct uptake of purified RLIP76 protein into mammalian cells from
      donor proteoliposomes confers DOX resistance. These results indicate that RLIP76,
      in addition to its role in signal transduction, can catalyze transport of
      glutathione conjugates and xenobiotics, and may contribute to the multidrug
      resistance phenomenon.

PMID- 10924129
TI  - Determination of transport kinetics of chick MCT3 monocarboxylate transporter
      from retinal pigment epithelium by expression in genetically modified yeast.
AB  - Monocarboxylate transporters (MCTs) comprise a group of highly homologous
      proteins that reside in the plasma membrane of almost all cells and which mediate
      the 1:1 electroneutral transport of a proton and a lactate ion. The isoform MCT3
      is restricted to the basal membrane of the retinal pigment epithelium where it
      regulates lactate levels in the neural retina. Kinetic analysis of this
      transporter poses formidable difficulties due to the presence of multiple lactate
      transporters and their complex interaction with MCTs in adjacent cells. To
      circumvent these problems, we expressed both the MCT3 gene and a green
      fluorescent protein-tagged MCT3 construct in Saccharomyces cerevisiae. Since L
      lactate metabolism in yeast depends on the CYB2 gene, we disrupted CYB2 to study
      the MCT3 transporter activity free from the complications of metabolism. Under
      these conditions L-lactate uptake varied inversely with pH, greater uptake being
      associated with lower pH. Whereas the V(max) was invariant, the K(m) increased
      severalfold as the pH rose from 6 to 8. In addition, MCT3 was highly resistant to
      a number of "classical" inhibitors of lactate transport. Last, studies with
      diethyl pyrocarbonate and p-chloromercuribenzenesulfonate set limitations on the
      locus of potential residues involved in the critical site of lactate
      translocation.

PMID- 10924130
TI  - Modulation of GLUT4 and GLUT1 recycling by insulin in rat adipocytes: kinetic
      analysis based on the involvement of multiple intracellular compartments.
AB  - The trafficking kinetics of GLUT4 and GLUT1 in rat epididymal adipocytes were
      analyzed by a four-compartment model based upon steady-state pool sizes of three
      intracellular fractions and one plasma membrane fraction separated and assessed
      under both basal and insulin-stimulated states. The steady-state compartment
      sizes provided relative values of the kinetic coefficients characterizing the
      rate of each process in the loop. Absolute values of these coefficients were
      obtained by matching the simulated half-times to those observed experimentally
      and reported in the literature for both basal and insulin-stimulated states. Our
      analysis revealed that insulin modulates the GLUT4 trafficking at multiple steps
      in the rat adipocyte, not only reducing the endocytotic rate constant 3-4-fold
      and increasing the exocytotic rate 8-24-fold but also increasing the two rate
      coefficients coupling the three intracellular compartments 2-6-fold each.
      Furthermore, GLUT1 was completely segregated from GLUT4 in two of the three
      intracellular compartments, and its steady-state distribution is consistent with
      a four-compartment model of GLUT1 recycling involving an insulin sensitive
      endocytosis step in common with the GLUT4 system, but with all other processes
      being insensitive to insulin.

PMID- 10924131
TI  - Cysteine-scanning mutagenesis of transmembrane segment 11 of the GLUT1
      facilitative glucose transporter.
AB  - The glucose permeation pathway within the GLUT1 facilitative glucose transporter
      is hypothesized to be formed by the juxtaposition of the hydrophilic faces of
      several transmembrane alpha-helices. The role of transmembrane segment 11 in
      forming a portion of this central aqueous channel was investigated using cysteine
      scanning mutagenesis in conjunction with sulfhydryl-directed chemical
      modification. Each of the amino acid residues within transmembrane segment 11
      were individually mutated to cysteine in an engineered GLUT1 molecule devoid of
      all native cysteines (C-less). Measurement of 2-deoxyglucose uptake in a Xenopus
      oocyte expression system revealed that all of these mutants retain measurable
      transport activity. Four of the cysteine mutants (N411, W412, N415, and F422) had
      significantly reduced specific activity relative to the C-less protein. Specific
      activity was increased in five of the mutants (A402, A405, V406, F416, and M420).
      The solvent accessibility and relative orientation of the residues to the glucose
      permeation pathway were investigated by determining the sensitivity of the mutant
      transporters to inhibition by the sulfhydryl-directed reagent p
      chloromercuribenzenesulfonate (pCMBS). Cysteine replacement at five positions
      (I404, G408, F416, G419, and M420) produced transporters that were inhibited by
      incubation with extracellular pCMBS. All of these residues cluster along a single
      face of the alpha-helix within the regions showing altered specific activities.
      These data demonstrate that the exofacial portion of transmembrane segment 11 is
      accessible to the external solvent and provide evidence for the positioning of
      this alpha-helix within or near the glucose permeation pathway.

PMID- 10924132
TI  - Characterization of interactions among the heme center, tetrahydrobiopterin, and
      L-arginine binding sites of ferric eNOS using imidazole, cyanide, and nitric
      oxide as probes.
AB  - Endothelial nitric oxide synthase (eNOS) is a self-sufficient P450-like enzyme. A
      P450 reductase domain is tethered to an oxygenase domain containing the heme, the
      substrate (L-arginine) binding site, and a cofactor, tetrahydrobiopterin (BH(4)).
      This "triad", located at the distal heme pocket, is the center of oxygen
      activation and enzyme catalysis. To probe the relationships among these three
      components, we examined the binding kinetics of three different small heme
      ligands in the presence and absence of either L-arginine, BH(4), or both.
      Imidazole binding was strictly competitive with L-arginine, indicating a domain
      overlap. BH(4) had no obvious effect on imidazole binding but slightly increased
      the k(on) for L-arginine. L-Arginine decreased the k(on) and k(off) for cyanide
      by two orders, indicating a "kinetic obstruction" mechanism. BH(4) slightly
      enhanced cyanide binding. Nitric oxide (NO) binding kinetics were more complex.
      Increasing the L-arginine concentration decreased the NO binding affinity at
      equilibrium. In both BH(4)-abundant and BH(4)-deficient eNOS, half of the NO
      binding sites showed a sizable decrease of the binding rate by L-arginine, with
      the rate of NO binding at the other half of the sites remaining essentially
      unaltered by L-arginine, implying that the two heme centers in the eNOS dimer are
      functionally distinct.

PMID- 10924133
TI  - Ca2+-assisted, direct hydride transfer, and rate-determining tautomerization of
      C5-reduced PQQ to PQQH2, in the oxidation of beta-D-glucose by soluble,
      quinoprotein glucose dehydrogenase.
AB  - Spectral and kinetic studies were performed on enzyme forms of soluble glucose
      dehydrogenase of the bacterium Acinetobacter calcoaceticus (sGDH) in which the
      PQQ-activating Ca(2+) was absent (Holo X) or was replaced with Ba(2+) (Ba-E) or
      in which PQQ was replaced with an analogue or a derivative called "nitroPQQ" (E
      NPQ). Although exhibiting diminished rates, just like sGDH, all enzyme forms were
      able to oxidize a broad spectrum of aldose sugars, and their reduced forms could
      be oxidized with the usual artificial electron acceptor. On inspection of the
      plots for the reductive half-reaction, it appeared that the enzyme forms
      exhibited a negative cooperativity effect similar to that of sGDH itself under
      turnover conditions, supporting the view that simultaneous binding of substrate
      to the two subunits of sGDH causes the effect. Stopped-flow spectroscopy of the
      reductive half-reaction of Ba-E with glucose showed a fluorescing transient
      previously observed in the reaction of sGDH with glucose-1-d, whereas no
      intermediate was detected at all in the reactions of E-NPQ and Holo X. Using
      hydrazine as a probe, the fluorescing C5 adduct of PQQ and hydrazine was formed
      in sGDH, Ba-E, and Holo X, but E-NPQ did not react with hydrazine. When this is
      combined with other properties of E-NPQ and the behavior of enzyme forms
      containing a PQQ analogue, we concluded that the catalytic potential of the
      cofactor in the enzyme is not determined by its adduct-forming ability but by
      whether it is or can be activated with Ca(2+), activation being reflected by the
      large red shift of the absorption maximum induced by this metal ion when binding
      to the reduced cofactor in the enzyme. This conclusion, together with the
      observed deuterium kinetic isotope effect of 7.8 on transient formation in Ba-E,
      and that already known on transient decay, indicate that the sequential steps in
      the mechanism of sGDH must be (1) reversible substrate binding, (2) direct
      transfer of a hydride ion (reversible or irreversible) from the C1 position of
      the beta-anomer of glucose to the C5 of PQQ, (3) irreversible, rate-determining
      tautomerization of the fluorescing, C5-reduced PQQ to PQQH(2) and release (or
      earlier) of the product, D-glucono-delta-lactone, and (4) oxidation of PQQH(2) by
      an electron acceptor. The PQQ-activating Ca(2+) greatly facilitates the reactions
      occurring in step 2. His144 may also play a role in this by acting as a general
      base catalyst, initiating hydride transfer by abstracting a proton from the
      anomeric OH group of glucose. The validity of the proposed mechanism is discussed
      for other PQQ-containing dehydrogenases.

PMID- 10924134
TI  - Characterization of the metal binding environment of catalytic site 1 of
      chloroplast F1-ATPase from Chlamydomonas.
AB  - Metal ligands of the VO(2+)-adenosine diphosphate (ADP) complex bound to high
      affinity catalytic site 1 of chloroplast F(1) adenosine triphosphatase (CF(1)
      ATPase) were characterized by electron paramagnetic resonance (EPR) spectroscopy.
      This EPR spectrum contains two EPR species designated E and F not observed when
      VO(2+)-nucleotide is bound to site 3 of CF(1). Site-directed mutations betaE197C,
      betaE197D, and betaE197S in Chlamydomonas CF(1) impair ATP synthase and ATPase
      activity catalyzed by CF(1)F(o) and soluble CF(1), respectively, indicating that
      this residue is important for enzyme function. These mutations caused large
      changes in the (51)V hyperfine tensors of VO(2+)-nucleotide bound to site 1 but
      not to site 3. Mutations to the Walker homology B aspartate betaD262C, betaD262H,
      and betaD262T of Chlamydomonas CF(1) caused similar effects on the EPR spectrum
      of VO(2+)-ADP bound to site 1. These results indicate that the conversion of the
      low-affinity site 3 conformation to high-affinity site 1 involves the
      incorporation betaE197 and betaD262 as metal ligands.

PMID- 10924135
TI  - Photochemical and mutational analysis of the FMN-binding domains of the plant
      blue light receptor, phototropin.
AB  - The plant photoreceptor phototropin is an autophosphorylating serine-threonine
      protein kinase activated by UV-A/blue light. Two domains, LOV1 and LOV2, members
      of the PAS domain superfamily, mediate light sensing by phototropin. Heterologous
      expression studies have shown that both domains function as FMN-binding sites.
      Although three plant blue light photoreceptors, cry1, cry2, and phototropin, have
      been identified to date, the photochemical reactions underlying photoactivation
      of these light sensors have not been described so far. Herein, we demonstrate
      that the LOV domains of Avena sativa phototropin undergo a self-contained
      photocycle characterized by a loss of blue light absorbance in response to light
      and a spontaneous recovery of the blue light-absorbing form in the dark. Rate
      constants and quantum efficiencies for the photoreactions indicate that LOV1
      exhibits a lower photosensitivity than LOV2. The spectral properties of the
      photoproduct produced for both LOV domains are unrelated to those found for
      photoreduced flavins and flavoproteins, but are consistent with those of a flavin
      cysteinyl adduct. Flavin-thiol adducts are generally short-lifetime reaction
      intermediates formed during the flavoprotein-catalyzed reduction of protein
      disulfides. By site-directed mutagenesis, we have identified several amino acid
      residues within the putative chromophore binding site of LOV1 and LOV2 that
      appear to be important for FMN binding and/or the photochemical reactivity. Among
      those is Cys39, which plays an important role in the photochemical reaction of
      the LOV domains. Replacement of Cys39 with Ala abolished the photochemical
      reactions of both LOV domains. We therefore propose that light sensing by the
      phototropin LOV domains occurs via the formation of a stable adduct between the
      FMN chromophore and Cys39.

PMID- 10924136
TI  - Exploring the membrane domain of the reduced nicotinamide adenine dinucleotide
      quinone oxidoreductase of Paracoccus denitrificans: characterization of the NQO7
      subunit.
AB  - The proton-translocating reduced nicotinamide adenine dinucleotide- (NADH-)
      quinone oxidoreductase (NDH-1) of Paracoccus denitrificans is composed of at
      least 14 different subunits (NQO1-14). In addition, this enzyme complex houses
      one flavin mononucleotide (FMN) and 7-8 iron-sulfur clusters as cofactors. The
      expression and partial characterization of the NQO7 subunit, one of the seven
      subunits that constitute the hydrophobic sector of the enzyme complex, have been
      performed and are reported here. Expression of the NQO7 subunit was achieved by
      use of the glutathione-S-transferase (GST) fusion system together with
      Escherichia coli strains BLR(DE3)pLysS and BL21(DE3)pLysS. The GST-fused NQO7
      subunit was expressed in the membrane fraction of the host cells and was
      extracted from the membranes by nonionic detergents (Triton X-100, dodecyl
      maltoside). The extracted polypeptide was purified by glutathione affinity column
      chromatography and characterized. The isolated GST-fused NQO7 subunit (but not
      the GST alone) was determined to interact with phospholipid vesicles and suppress
      the membrane fluidity. Antibodies against both the N- and C-terminal regions of
      the deduced primary structure of the NQO7 subunit reacted with a single band (15
      kDa) of the Paracoccus membranes. By use of immunochemical and cysteine residue
      modification techniques, the topology of the Paracoccus NQO7 subunit in the
      membranes has been examined. The data suggest that the Paracoccus NQO7 subunit
      contains three transmembrane segments and that its N- and C-terminal regions are
      directed toward the cytoplasmic and periplasmic phases of the membrane,
      respectively. The proposed topology of the GST-fused NQO7 subunit expressed in E.
      coli membranes is consistent with that of the NQO7 subunit in the Paracoccus
      membranes.

PMID- 10924137
TI  - The FMN-binding domain of cytochrome P450BM-3: resolution, reconstitution, and
      flavin analogue substitution.
AB  - Cytochrome P450BM-3 is a self-sufficient bacterial protein containing three
      naturally fused domains which bind either heme, FMN, or FAD. Resolution of
      protein and FMN from the isolated FMN-containing domain of cytochrome
      P450Betamicro-3 was accomplished using trichloroacetic acid. The apoprotein thus
      prepared was shown to rebind FMN to regenerate the original holoprotein as
      indicated by both spectroscopy and activity measurements. To better understand
      how the protein/flavin interaction might contribute to reactivity, the
      association process was studied in detail. Fluorescence quenching was used to
      measure a dissociation constant of the flavin-protein complex of 31 nM,
      comparable to FMN-containing proteins of similar reactivity and higher than that
      of flavodoxins. Stopped-flow kinetics were performed, and a multistep binding
      process was indicated, with an initial k(on) value of 1.72 x 10(5) M(-)(1) s(
      )(1). Preparation of the apoprotein allowed substitution of flavin analogues for
      the native FMN cofactor using 8-chloro-FMN and 8-amino-FMN. Both were found to
      bind efficiently to the protein with only minor variations in affinity. Reductive
      titrations established that, as in the native FMN-containing FMN-binding domain,
      the 8-amino-FMN-substituted domain does not produce a stable one-electron-reduced
      species during titration with sodium dithionite. The 8-chloro-FMN-substituted
      domain, however, had sufficiently altered redox properties to form a stable red
      anionic semiquinone. The 8-chloro-FMN-substituted FMN-binding domain was shown in
      reconstituted systems to retain most of the cytochrome c reductase activity of
      the native domain but only a very small amount of palmitic acid hydroxylase
      activity. The 8-amino-FMN-substituted FMN-binding domain showed no palmitic acid
      hydroxylase activity and only 30% of the native cytochrome c reductase activity,
      demonstrating the importance of thermodynamics to the mechanism of this protein.

PMID- 10924138
TI  - Effects of deletions at the carboxyl terminus of Zymomonas mobilis pyruvate
      decarboxylase on the kinetic properties and substrate specificity.
AB  - The three-dimensional structure of Zymomonas mobilis pyruvate decarboxylase shows
      that the carboxyl-terminal region of the protein occludes the active site. This
      observation is consistent with earlier suggestions that the active site is
      inaccessible to solvent during catalysis. However, the carboxyl-terminal region
      must move aside to allow entry of the substrate, and again to permit the products
      to leave. Here we have examined the role of the carboxyl terminus by making 15
      variants of the enzyme with serial deletions. The activity is largely unaffected
      by removal of up to seven residues but deletion of the next two, R561 and S560,
      results in a drastic loss of activity. Five of these deletion mutants were
      purified and fully characterized and showed progressive decreases in activity, in
      the ability to discriminate between pyruvate and larger substrates, and in
      cofactor affinity. Several substitution mutants at residues R561 and S560 were
      prepared, purified, and fully characterized. The results indicate important roles
      for the side-chain of R561 and the backbone atoms of S560. It is suggested that
      the carboxyl-terminal region of pyruvate decarboxylase is needed to lock in the
      cofactors and for the proper closure of the active site that is required for
      discrimination between substrates and for decarboxylation to occur.

PMID- 10924139
TI  - Biosynthesis of the prosthetic group of citrate lyase.
AB  - Citrate lyase (EC 4.1.3.6) catalyzes the cleavage of citrate to acetate and
      oxaloacetate and is composed of three subunits (alpha, beta, and gamma). The
      gamma-subunit serves as an acyl carrier protein (ACP) and contains the prosthetic
      group 2'-(5' '-phosphoribosyl)-3'-dephospho-CoA, which is attached via a
      phosphodiester linkage to serine-14 in the enzyme from Klebsiella pneumoniae. In
      this work, we demonstrate by genetic and biochemical studies with citrate lyase
      of Escherichia coli and K. pneumoniae that the conversion of apo-ACP into holo
      ACP is dependent on the two proteins, CitX (20 kDa) and CitG (33 kDa). In the
      absence of CitX, only apo-ACP was synthesized in vivo, whereas in the absence of
      CitG, an adenylylated ACP was produced, with the AMP residue attached to serine
      14. The adenylyltransferase activity of CitX could be verified in vitro with
      purified CitX and apo-ACP plus ATP as substrates. Besides ATP, CTP, GTP, and UTP
      also served as nucleotidyl donors in vitro, showing that CitX functions as a
      nucleotidyltransferase. The conversion of apo-ACP into holo-ACP was achieved in
      vitro by incubation of apo-ACP with CitX, CitG, ATP, and dephospho-CoA. ATP could
      not be substituted with GTP, CTP, UTP, ADP, or AMP. In the absence of CitG or
      dephospho-CoA, AMP-ACP was formed. Remarkably, it was not possible to further
      convert AMP-ACP to holo-ACP by subsequent incubation with CitG and dephospho-CoA.
      This demonstrates that AMP-ACP is not an intermediate during the conversion of
      apo- into holo-ACP, but results from a side activity of CitX that becomes
      effective in the absence of its natural substrate. Our results indicate that holo
      ACP formation proceeds as follows. First, a prosthetic group precursor
      [presumably 2'-(5' '-triphosphoribosyl)-3'-dephospho-CoA] is formed from ATP and
      dephospho-CoA in a reaction catalyzed by CitG. Second, holo-ACP is formed from
      apo-ACP and the prosthetic group precursor in a reaction catalyzed by CitX.

PMID- 10924140
TI  - Mutation of Arg-166 of alkaline phosphatase alters the thio effect but not the
      transition state for phosphoryl transfer. Implications for the interpretation of
      thio effects in reactions of phosphatases.
AB  - It has been suggested that the mechanism of alkaline phosphatase (AP) is
      associative, or triester-like, because phosphorothioate monoesters are hydrolyzed
      by AP approximately 10(2)-fold slower than phosphate monoesters. This "thio
      effect" is similar to that observed for the nonenzymatic hydrolysis of phosphate
      triesters, and is the inverse of that observed for the nonenzymatic hydrolysis of
      phosphate monoesters. The latter reactions proceed by loose, dissociative
      transition states, in contrast to reactions of triesters, which have tight,
      associative transition states. Wild-type alkaline phosphatase catalyzes the
      hydrolysis of p-nitrophenyl phosphate approximately 70 times faster than p
      nitrophenyl phosphorothioate. In contrast, the R166A mutant alkaline phosphatase
      enzyme, in which the active site arginine at position 166 is replaced with an
      alanine, hydrolyzes p-nitrophenyl phosphate only about 3 times faster than p
      nitrophenyl phosphorothioate. Despite this approximately 23-fold change in the
      magnitude of the thio effects, the magnitudes of Bronsted beta(lg) for the native
      AP (-0.77 +/- 0.09) and the R166A mutant (-0.78 +/- 0. 06) are the same. The
      identical values for the beta(lg) indicate that the transition states are similar
      for the reactions catalyzed by the wild-type and the R166A mutant enzymes. The
      fact that a significant change in the thio effect is not accompanied by a change
      in the beta(lg) indicates that the thio effect is not a reliable reporter for the
      transition state of the enzymatic phosphoryl transfer reaction. This result has
      important implications for the interpretation of thio effects in enzymatic
      reactions.

PMID- 10924141
TI  - Functional importance of motif I of pseudouridine synthases: mutagenesis of
      aligned lysine and proline residues.
AB  - On the basis of sequence alignments, the pseudouridine synthases were grouped
      into four families that share no statistically significant global sequence
      similarity, though some common sequence motifs were discovered [Koonin, E. V.
      (1996) Nucleic Acids. Res. 24, 2411-2415; Gustafsson, C., Reid, R., Greene, P.
      J., and Santi, D. V. (1996) Nucleic Acids Res. 24, 3756-3762]. We have
      investigated the functional significance of these alignments by substituting the
      nearly invariant lysine and proline residues in Motif I of RluA and TruB,
      pseudouridine synthases belonging to different families. Contrary to our
      expectations, the altered enzymes display only very mild kinetic impairment.
      Substitution of the aligned lysine and proline residues does, however, reduce
      structural stability, consistent with a temperature sensitive phenotype that
      results from substitution of the cognate proline residue in Cbf5p, a yeast
      homologue of TruB [Zerbarjadian, Y., King, T., Fournier, M. J., Clarke, L., and
      Carbon, J. (1999) Mol. Cell. Biol. 19, 7461-7472]. Together, our data support a
      functional role for Motif I, as predicted by sequence alignments, though the
      effect of substituting the highly conserved residues was milder than we
      anticipated. By extrapolation, our findings also support the assignment of
      pseudouridine synthase function to certain physiologically important eukaryotic
      proteins that contain Motif I, including the human protein dyskerin, alteration
      of which leads to the disease dyskeratosis congenita.

PMID- 10924142
TI  - Real-time kinetic studies on the interaction of transforming growth factor alpha
      with the epidermal growth factor receptor extracellular domain reveal a
      conformational change model.
AB  - Transforming growth factor alpha (TGF-alpha), epidermal growth factor (EGF), and
      related factors mediate their biological effects by binding to the extracellular
      domain of the EGF receptor, which leads to activation of the receptor's
      cytoplasmic tyrosine kinase activity. Much remains to be determined, however,
      about the detailed molecular mechanism involved in this ligand-induced receptor
      activation. The determination of the binding mechanism and the related
      thermodynamic and kinetic parameters are of prime importance. To do so, we have
      used a surface plasmon resonance-based biosensor (the BIAcore) that allows the
      real-time recording of the interaction between TGF-alpha and the extracellular
      domain of the EGF receptor. By immobilizing different biotinylated derivatives of
      TGF-alpha on the sensor chip surface, we demonstrated that the N-terminus of TGF
      alpha is not directly involved in receptor binding. By optimizing experimental
      conditions and interpreting the biosensor results by several data analysis
      methods, we were able to show that the data do not fit a simple binding model.
      Through global analysis of the data using a numerical integration method, we
      tested several binding mechanisms for the TGF-alpha/EGF receptor interaction and
      found that a conformational change model best fits the biosensor data. Our
      results, combined with other analyses, strongly support a receptor activation
      mechanism in which ligand binding results in a conformation-driven exposure of a
      dimerization site on the receptor.

PMID- 10924143
TI  - GPI-linked proteins do not transfer spontaneously from erythrocytes to liposomes.
      New aspects of reorganization of the cell membrane.
AB  - Exposure of cells to liposomes results in the release of integral membrane
      proteins. However, it is still controversial whether the release is due to
      spontaneous protein transfer from cells to liposomes or shed vesicles released
      from cells. We investigated this issue in an erythrocyte-liposome system by
      examining the location of acetylcholinesterase (AChE, an integral membrane
      protein marker), cholesterol (erythrocyte membrane lipid marker), hemoglobin
      (cytosolic protein marker), and a nonexchangeable lipid marker in liposomes in a
      sucrose density gradient at high resolution. The density distribution showed that
      AChE is not transferred to the liposomes but is located on small (about 50 nm)
      light (10-20 wt % sucrose) or large (about 200 nm) heavy shed vesicles (more than
      30 wt % sucrose). AChE in the light shed-vesicle fraction markedly increased even
      after its level in the heavy fraction reached a plateau. AChE was also released
      from isolated heavy shed vesicles and accumulated in the small light shed-vesicle
      fraction in the presence of liposomes. After incubation of spherical erythrocytes
      (morphological index, 5.0) with liposomes, AChE hardly appeared in the heavy shed
      vesicle fraction, and the majority (>99%) appeared in the light shed-vesicle
      fraction, indicating that AChE is released from both the erythrocytes and heavy
      shed vesicles to the light shed-vesicle fraction, which becomes rich in AChE. Our
      results demonstrated for the first time that GPI-linked proteins do not
      spontaneously transfer from erythrocytes to liposomes. Our study also suggests
      that in vivo GPI-linked membrane proteins do not spontaneously transfer between
      cell membranes but that some catalyst is needed.

PMID- 10924145
TI  - On the concentrations of cyclins and cyclin-dependent kinases in extracts of
      cultured human cells.
AB  - Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the human cell
      cycle. Here we have directly measured the concentrations of the G(1) and G(2)
      cyclins and their CDK partners in highly synchronized human cervical carcinoma
      cells (HeLa). To determine the exact concentrations of cyclins and CDKs in the
      cell extracts, we developed a relatively simple method that combined the use of
      (35)S-labeled standards produced in rabbit reticulocyte lysates and
      immunoblotting with specific antibodies. Using this approach, we formally
      demonstrated that CDC2 and CDK2 are in excess of their cyclin partners. We found
      that the concentrations of cyclin A2 and cyclin B1 (at their peak levels in the
      G(2) phase) were about 30-fold less than that of their partner CDC2. The peak
      levels of cyclin A2 and cyclin E1, at the G(2) phase and G(1) phase,
      respectively, were only about 8-fold less than that of their partner CDK2. These
      ratios are in good agreement with size fractionation analysis of the relative
      amount of monomeric and complexed forms of CDC2 and CDK2 in the cell. All the
      cyclin A2 and cyclin E1 are in complexes with CDC2 and CDK2, but there are some
      indications that a significant portion of cyclin B1 may not be in complex with
      CDC2. Furthermore, we also demonstrated that the concentration of the CDK
      inhibitor p21(CIP1/WAF1) induced after DNA damage is sufficient to overcome the
      cyclin-CDK2 complexes in MCF-7 cells. These direct quantitations formally
      confirmed the long-held presumption that CDKs are in excess of the cyclins in the
      cell. Moreover, similar approaches can be used to measure the concentration of
      any protein in cell-free extracts.

PMID- 10924146
TI  - Quinoxaline antibiotics enhance peptide nucleic acid binding to double-stranded
      DNA.
AB  - The effects of a wide range of DNA binding drugs on peptide nucleic acid (PNA)
      binding to double-stranded DNA by strand displacement have been investigated
      using a gel retardation assay. The bis-PNA [H-(Lys)-TTJTTJTTTT-(eg)(3)-TTTTCTTCTT
      Lys-NH(2)] was used together with a 248 bp DNA fragment containing an appropriate
      target for the PNA. Most of the ligands that were studied, including DNA minor
      groove binders as well as intercalators and bis-intercalators, either have no
      effect or strongly inhibit PNA binding to DNA. By contrast, quinoxaline
      antibiotics facilitate PNA-DNA complex formation. The "PNA-helper" effect of
      echinomycin was studied in more detail using time and temperature dependence
      experiments to elucidate the mechanism. PNA binding to DNA follows pseudo-first
      order kinetics, but the initial rate of binding is accelerated more than 10-fold
      in the presence of 10 microM echinomycin. The activation energy for PNA binding
      to dsDNA is lowered 2-fold by the antibiotic (45 vs 90 kJ/mol in the control).
      The reasons why quinoxalines promote the binding of PNA to DNA are not entirely
      clear but may well include distortions (opening) of the double helix that
      facilitate PNA invasion. This study establishes that the efficacy of DNA-targeted
      PNA antigene molecules could potentially be enhanced by judiciously adding
      certain DNA-interactive ligands.

PMID- 10924144
TI  - Attractant regulation of the aspartate receptor-kinase complex: limited
      cooperative interactions between receptors and effects of the receptor
      modification state.
AB  - The manner by which the bacterial chemotaxis system responds to a wide range of
      attractant concentrations remains incompletely understood. In principle, positive
      cooperativity between chemotaxis receptors could explain the ability of bacteria
      to respond to extremely low attractant concentrations. By utilizing an in vitro
      receptor-coupled kinase assay, the attractant-dependent response curve has been
      measured for the Salmonella typhimurium aspartate chemoreceptor. The attractant
      chosen, alpha-methyl aspartate, was originally used to quantitate high receptor
      sensitivity at low attractant concentrations by Segall, Block, and Berg [(1986)
      Proc. Natl. Acad. Sci. U.S.A. 83, 8987-8991]. The attractant response curve
      exhibits limited positive cooperativity, yielding a Hill coefficient of 1.7-2.4,
      and this Hill coefficient is relatively independent of both the receptor
      modification state and the mole ratio of CheA to receptor. These results disfavor
      models in which there are strong cooperative interactions between large numbers
      of receptor dimers in an extensive receptor array. Instead, the results are
      consistent with cooperative interactions between a small number of coupled
      receptor dimers. Because the in vitro receptor-coupled kinase assay utilizes
      higher than native receptor densities arising from overexpression, the observed
      positive cooperativity may overestimate that present in native receptor
      populations. Such positive cooperativity between dimers is fully compatible with
      the negative cooperativity previously observed between the two symmetric ligand
      binding sites within a single dimer. The attractant affinity of the aspartate
      receptor is found to depend on the modification state of its covalent adaptation
      sites. Increasing the the level of modification decreases the apparent attractant
      affinity at least 10-fold in the in vitro receptor-coupled kinase assay. This
      observation helps explain the ability of the chemotaxis pathway to respond to a
      broad range of attractant concentrations in vivo.

PMID- 10924147
TI  - Two DNA polymerases of Escherichia coli display distinct misinsertion
      specificities for 2-hydroxy-dATP during DNA synthesis.
AB  - The insertion specificities of an oxidized dATP analogue, 2-hydroxydeoxyadenosine
      5'-triphosphate (2-OH-dATP), were determined using the alpha (catalytic) subunit
      of Escherichia coli DNA polymerase III and the exonuclease-deficient Klenow
      fragment of DNA polymerase I. In contrast to our previous observation that
      mammalian DNA polymerase alpha incorporated the oxidized nucleotide opposite T
      and C, these two E. coli DNA polymerases incorporated 2-OH-dATP opposite T and G
      on the DNA template. Steady-state kinetic studies indicated that the alpha
      subunit incorporated 2-OH-dATP 10 times more frequently opposite T than opposite
      G. On the other hand, the incorporation of 2-OH-dATP opposite T by the
      exonuclease-deficient Klenow fragment was 2 orders of magnitude more efficient
      than that opposite G. These results indicate that the misinsertion specificity of
      2-OH-dATP differs between replicative and repair-type DNA polymerases, and
      provide a biochemical basis for the mutations induced by 2-OH-dATP in E. coli.

PMID- 10924148
TI  - Oxidative damage generated by an oxo-metalloporphyrin onto the human telomeric
      sequence.
AB  - The cationic metalloporphyrin Mn-TMPyP activated by KHSO(5) has been used as
      cleaver of an oligonucleotide containing the four human telomere repeats of 5'
      GGGTTA. This oligonucleotide formed an intramolecular quadruplex DNA under 200 mM
      KCl as probed by DMS footprinting and could fold into different quadruplex
      structures under 200 mM NaCl. We found that the oxo-metalloporphyrin was able to
      mediate efficient oxidative cleavage of the quadruplex. The location of damage
      showed that the metalloporphyrin was able to bind to the last G-tetrad of the
      quadruplex structure via an external interaction. This metalloporphyrin-G-tetrad
      interaction needs a relatively high flexibility of the single-stranded linker
      regions to allow the partial stacking of the metalloporphyrin with the last G
      tetrad planar structure. The oxidative damage consisted of guanine oxidation
      within the interacting G-tetrad together with an 1'-carbon hydroxylation of
      deoxyribose residues of the thymidine residues located on the neighboring single
      stranded loop. So the high-valent oxo-metalloporphyrin is able to mediate both
      electron-abstraction or H-abstraction on G or T residues, respectively, within
      the DNA quadruplex target.

PMID- 10924149
TI  - Experimental and theoretical analysis of the invasive signal amplification
      reaction.
AB  - The invasive signal amplification reaction is a sensitive method for single
      nucleotide polymorphism detection and quantitative determination of viral load
      and gene expression. The method requires the adjacent binding of upstream and
      downstream oligonucleotides to a target nucleic acid (either DNA or RNA) to form
      a specific substrate for the structure-specific 5' nucleases that cleave the
      downstream oligonucleotide to generate signal. By running the reaction at an
      elevated temperature, the downstream oligonucleotide cycles on and off the target
      leading to multiple cleavage events per target molecule without temperature
      cycling. We have examined the performance of the FEN1 enzymes from Archaeoglobus
      fulgidus and Methanococcus jannaschii and the DNA polymerase I homologues from
      Thermus aquaticus and Thermus thermophilus in the invasive signal amplification
      reaction. We find that the reaction has a distinct temperature optimum which
      increases with increasing length of the downstream oligonucleotide. Raising the
      concentration of either the downstream oligonucleotide or the enzyme increases
      the reaction rate. When the reaction is configured to cycle the upstream instead
      of the downstream oligonucleotide, only the FEN1 enzymes can support a high level
      of cleavage. To investigate the origin of the background signal generated during
      the invasive reaction, the cleavage rates for several nonspecific substrates that
      arise during the course of a reaction were measured and compared with the rate of
      the specific reaction. We find that the different 5' nuclease enzymes display a
      much greater variability in cleavage rates on the nonspecific substrates than on
      the specific substrate. The experimental data are compared with a theoretical
      model of the invasive signal amplification reaction.

PMID- 10924150
TI  - Identification of hydrophobic amino acid residues involved in the formation of
      S100P homodimers in vivo.
AB  - S100 proteins are small dimeric members of the EF-hand superfamily of Ca(2+)
      binding proteins thought to participate in mediating intracellular Ca(2+) signals
      by binding to and thereby regulating target proteins in a Ca(2+)-dependent
      manner. As dimer formation is crucial to S100 function, we applied a yeast two
      hybrid approach in analyzing in vivo molecular aspects of S100 dimerization. We
      chose S100P, a member of the S100 family highly expressed in placenta, for
      detailed analysis and showed that S100P monomers strongly interact with one
      another but not with other S100 polypeptides, indicating that homodimer formation
      is obligatory for S100P. Analysis of the interaction of site-specific S100P
      mutants with the wild-type polypeptide or with other S100P mutant chains
      identifies conserved hydrophobic amino acid residues involved in mediating
      dimerization in vivo. Of these residues, F-15 is crucially important as a
      mutation to alanine abolishes dimerization even when the F15A S100P mutant
      polypeptide is allowed to interact with a wild-type chain. On the other hand, I
      11, I-12, or F-89 need to be replaced by a less hydrophopic residue in both
      subunits for there to be a similar extent of interfere with dimerization. This
      proves that hydrophobic residues implicated through structural studies in S100
      dimerization are involved in the dimer interaction in vivo and argues for a
      hierarchy of hydrophobic contacts stabilizing the dimer and thereby regulating
      S100 function.

PMID- 10924151
TI  - Multistate equilibrium unfolding of Escherichia coli dihydrofolate reductase:
      thermodynamic and spectroscopic description of the native, intermediate, and
      unfolded ensembles.
AB  - The thermodynamic and spectroscopic properties of a cysteine-free variant of
      Escherichia coli dihydrofolate reductase (AS-DHFR) were investigated using the
      combined effects of urea and temperature as denaturing agents. Circular dichroism
      (CD), absorption, and fluorescence spectra were recorded during temperature
      induced unfolding at different urea concentrations and during urea-induced
      unfolding at different temperatures. The first three vectors obtained by singular
      value decomposition of each set of unfolding spectra were incorporated into a
      global analysis of a unique thermodynamic model. Although individual unfolding
      profiles can be described as a two-state process, a simultaneous fit of 99
      vectors requires a three-state model as the minimal scheme to describe the
      unfolding reaction along both perturbation axes. The model, which involves native
      (N), intermediate (I), and unfolded (U) states, predicts a maximum apparent
      stability, DeltaG degrees (NU), of 6 kcal mol(-)(1) at 15 degrees C, an apparent
      m(NU) value of 2 kcal mol(-)(1) M(-)(1), and an apparent heat capacity change,
      DeltaC(p)()(-NU), of 2.5 kcal mol(-)(1) K(-)(1). The intermediate species has a
      maximum stability of approximately 2 kcal mol(-)(1) and a compactness closer to
      that of the native than to that of the unfolded state. The population of the
      intermediate is maximal ( approximately 70%) around 50 degrees C and falls below
      the limits of detection of > or =2 M urea or at temperatures of <35 or >65
      degrees C. The fluorescence properties of the equilibrium intermediate resemble
      those of a transient intermediate detected during refolding from the urea
      denatured state, suggesting that a tryptophan-containing hydrophobic cluster in
      the adenosine-binding domain plays a key role in both the equilibrium and kinetic
      reactions. The CD spectroscopic properties of the native state reveal the
      presence of two principal isoforms that differ in ligand binding affinities and
      in the packing of the adenosine-binding domain. The relative populations of these
      species change slightly with temperature and do not depend on the urea
      concentration, implying that the two native isoforms are well-structured and
      compact. Global analysis of data from multiple spectroscopic probes and several
      methods of unfolding is a powerful tool for revealing structural and
      thermodynamic properties of partially and fully folded forms of DHFR.

PMID- 10924152
TI  - The Met99Gln mutant of amicyanin from Paracoccus versutus.
AB  - The axial copper ligand methionine has been replaced by a glutamine in the
      cupredoxin amicyanin from Paracoccus versutus. Dynamic and structural
      characteristics of the mutant have been studied in detail using UV/Vis, EPR, NMR,
      cyclic voltammetry, and isomorphous metal replacement. M99Q amicyanin is a blue
      copper protein with significant spectral and structural similarities to the other
      cupredoxins umecyanin, stellacyanin, and M121Q azurin. In addition, the
      functional properties of M99Q amicyanin, as reflected in the electron self
      exchange rate constant and midpoint potential (165 mV), have been assessed and
      compared to values for M121Q azurin. For the latter protein, the published
      midpoint potential was corrected to the much lower value of 147 mV at pH 7, I =
      0.1 M. These values are very similar to the midpoint potential of stellacyanin,
      which naturally possesses an axial glutamine ligand and has the lowest reduction
      potential for a naturally occurring cupredoxin. A remarkable feature of M99Q
      amicyanin, in the reduced state, is the relatively high pK(a) value of 7.1 for
      its His96 ligand.

PMID- 10924153
TI  - Lysine 2,3-aminomutase and trans-4,5-dehydrolysine: characterization of an
      allylic analogue of a substrate-based radical in the catalytic mechanism.
AB  - An analogue of lysine, trans-4,5-dehydro-L-lysine (trans-4, 5-dehydrolysine), is
      a potent inhibitor of lysine 2,3-aminomutase from Clostridium subterminale SB4
      that competes with L-lysine for binding to the active site. Inclusion of trans
      4,5-dehydrolysine with activated enzyme and the coenzymes pyridoxal-5'-phosphate
      and S-adenosylmethionine, followed by freezing at 77 K, produces an intense
      signal in the electron paramagnetic resonance (EPR) spectrum at g 2.0, which is
      characteristic of an organic radical. A series of deuterated and (15)N-labeled
      samples of trans-4,5-dehydrolysine were synthesized and used to generate the EPR
      signal. Substitution of deuterium for hydrogen at C2, C3, C4, C5, and C6 of trans
      4, 5-dehydrolysine led to significant simplifications and narrowing of the EPR
      signal, showing that the unpaired electron was located on the carbon skeleton of
      4,5-trans-4,5-dehydrolysine. The hyperfine splitting pattern is simplified by use
      of 4,5-dehydro[3, 3-(2)H(2)]lysine or 4,5-dehydro[4,5-(2)H(2)]lysine, and it is
      dramatically simplified with 4,5-dehydro-[3,3,4,5,6,6-(2)H(6)]lysine. Spectral
      simulations show that the EPR signal arises from the allylic radical resulting
      from the abstraction of a hydrogen atom from C3 of trans-4,5-dehydrolysine. This
      radical is an allylic analogue of the substrate-related radical in the
      rearrangement mechanism postulated for this enzyme. The rate constant for
      formation of the 4,5-dehydrolysyl radical (2 min(-)(1)) matches that for the
      decrease in the concentration of [4Fe-4S](+), showing that the two processes are
      coupled. The cleavage of S-adenosylmethionine to 5'-deoxyadenosine and methionine
      takes place with a rate constant of approximately 5 min(-)(1). These kinetic
      correlations support the hypothesis that radical formation results from a
      reversible reaction between [4Fe-4S](+) and S-adenosylmethionine at the active
      site to form [4Fe-4S](2+), the 5'-deoxyadenosyl radical, and methionine as
      intermediates.

PMID- 10924154
TI  - Properties and reactivity of myoglobin reconstituted with chemically modified
      protohemin complexes.
AB  - The synthetic complexes protohemin-6(7)-L-arginyl-L-alanine (HM-RA) and
      protohemin-6(7)-L-histidine methyl ester (HM-H) were prepared by condensation of
      suitably protected Arg-Ala or His residues with protohemin IX. HM-RA and HM-H
      were used for reconstitution of apomyoglobin from horse heart, yielding the Mb-RA
      and Mb-H derivatives, respectively, of the protein. The spectral, binding and
      catalytic properties of Mb-RA and Mb-H are significantly different from those of
      Mb. As shown by MM and MD calculations, these differences are determined by some
      local structural changes around the heme which are generated by increased
      mobility of a key peptide segment (Phe43-Lys47), containing the residue (Lys45)
      that in native Mb interacts with one of the porphyrin carboxylate groups. In the
      reconstituted Mbs this carboxylate group is bound to the Arg-Ala or His residue
      and is no longer available for electrostatic interaction with Lys45. The mobility
      of the peptide segment near the active site allows the distal histidine to come
      to a closer contact with the heme, and in fact Mb-RA and Mb-H exist as an
      equilibrium between a high-spin form and a major low-spin, six-coordinated form
      containing a bis-imidazole ligated heme. The two forms are clearly
      distinguishable in the NMR spectra, that also show that each of them consists of
      a mixture of the two most stable isomers resulting from cofactor reconstitution,
      as also anticipated by MM and MD calculations. Exogenous ligands such as cyanide,
      azide, or hydrogen peroxide can displace the bound distal histidine, but their
      affinity is reduced. On the other hand, mobilization of the peptide chain around
      the heme in the reconstituted Mbs increases the accessibility of large donor
      molecules at the heme periphery, with respect to native Mb, where a rigid
      backbone limits access to the distal pocket. The increased active site
      accessibility of Mb-RA and Mb-H facilitates the binding and electron transfer of
      phenolic substrates in peroxidase-type oxidations catalyzed by the reconstituted
      proteins in the presence of hydrogen peroxide.

PMID- 10924155
TI  - New probes of the F1-ATPase catalytic transition state reveal that two of the
      three catalytic sites can assume a transition state conformation simultaneously.
AB  - MgADP in combination with fluoroscandium (ScFx) is shown to form a potently
      inhibitory, tightly bound, noncovalent complex at the catalytic sites of F(1)
      ATPase. The F(1).MgADP.ScFx complex mimics a catalytic transition state. Notably,
      ScFx caused large enhancement of MgADP binding affinity at both catalytic sites 1
      and 2, with little effect at site 3. These results indicate that sites 1 and 2
      may form a transition state conformation. A new direct optical probe of F(1)
      ATPase catalytic transition state conformation is also reported, namely,
      substantial enhancement of fluorescence emission of residue beta-Trp-148 observed
      upon binding of MgADP.ScFx or MgIDP. ScFx. Using this fluorescence signal,
      titrations were performed with MgIDP.ScFx which demonstrated that catalytic sites
      1 and 2 can both form a transition state conformation but site 3 cannot.
      Supporting data were obtained using MgIDP-fluoroaluminate. Current models of the
      MgATP hydrolysis mechanism uniformly make the assumption that only one catalytic
      site hydrolyzes MgATP at any one time. The fluorometal analogues demonstrate that
      two sites have the capability to form the transition state simultaneously.

PMID- 10924156
TI  - Histidine-607 and histidine-643 provide important interactions for metal support
      of catalysis in phosphodiesterase-5.
AB  - Class I cyclic nucleotide phosphodiesterases (PDEs) share a catalytic domain
      containing 18 invariant residues. In cGMP-binding cGMP-specific PDE (PDE5), we
      showed previously that point mutation of nine of these profoundly decreases
      k(cat) when the assay is conducted in the presence of Mg(2+); seven of these are
      in the prototypical metal-binding motifs A and B (HX(3)HX(n)()E) that we
      identified earlier. Tandem arrangement of two of these metal-binding motifs in
      PDEs is novel, and whether residues within these motifs are involved in metal
      support of catalytic activity is a fundamental question in this field. This
      report shows that mutation of either His-607 (A motif) or His-643 (B motif) to
      alanine profoundly diminishes support of PDE catalysis by Mn(2+) or Mg(2+), but
      mutation of His-647 in B motif or of Glu in either motif does not. H607A and
      H643A mutants have much greater maximum catalytic rates supported by Mn(2+) than
      that by Mg(2+); catalytic activity of H603A mutant is supported weakly by either.
      In H607A and H643A, K(a)s for Mn(2+) and Mg(2+) are increased, but the effect of
      Mn(2+) is 2-fold greater than that of Mg(2+) in each. Mutation of any of the
      other conserved residues (Asn-604, Asp-644, His-675, Asp-714, and Asp-754) causes
      unremarkable changes in Mn(2+) or Mg(2+) support of catalysis. This study
      identifies specific residues in PDE5 that contribute to interactions with
      catalytically relevant metals. The combined data suggest that despite a high
      degree of sequence similarity between each HX(3)HX(n)()E motif in PDEs and
      certain metallo-endopeptidases, PDEs employ a distinct complement of residues for
      interacting with metals involved in catalysis.

PMID- 10924157
TI  - Kinetics and crystal structure of the wild-type and the engineered Y101F mutant
      of Herpes simplex virus type 1 thymidine kinase interacting with (North)
      methanocarba-thymidine.
AB  - Kinetic and crystallographic analyses of wild-type Herpes simplex virus type 1
      thymidine kinase (TK(HSV1)) and its Y101F-mutant [TK(HSV1)(Y101F)] acting on the
      potent antiviral drug 2'-exo-methanocarba-thymidine (MCT) have been performed.
      The kinetic study reveals a 12-fold K(M) increase for thymidine processed with
      Y101F as compared to the wild-type TK(HSV1). Furthermore, MCT is a substrate for
      both wild-type and mutant TK(HSV1). Its binding affinity for TK(HSV1) and
      TK(HSV1)(Y101F), expressed as K(i), is 11 microM and 51 microM, respectively,
      whereas the K(i) for human cytosolic thymidine kinase is as high as 1.6 mM,
      rendering TK(HSV1) a selectivity filter for antiviral activity. Moreover,
      TK(HSV1)(Y101F) shows a decrease in the quotient of the catalytic efficiency
      (k(cat)/K(M)) of dT over MCT corresponding to an increased specificity for MCT
      when compared to the wild-type enzyme. Crystal structures of wild-type and mutant
      TK(HSV1) in complex with MCT have been determined to resolutions of 1.7 and 2.4
      A, respectively. The thymine moiety of MCT binds like the base of dT while the
      conformationally restricted bicyclo[3.1.0]hexane, mimicking the sugar moiety,
      assumes a 2'-exo envelope conformation that is flatter than the one observed for
      the free compound. The hydrogen bond pattern around the sugar-like moiety differs
      from that of thymidine, revealing the importance of the rigid conformation of MCT
      with respect to hydrogen bonds. These findings make MCT a lead compound in the
      design of resistance-repellent drugs for antiviral therapy, and mutant Y101F, in
      combination with MCT, opens new possibilities for gene therapy.

PMID- 10924158
TI  - Recombinant antitoxic and antiinflammatory factor from the nonvenomous snake
      Python reticulatus: phospholipase A2 inhibition and venom neutralizing potential.
AB  - From the serum of the nonvenomous snake Python reticulatus, a new phospholipase
      A(2) (PLA(2)) inhibitor termed phospholipase inhibitor from python (PIP) was
      purified by sequential chromatography and cloned to elucidate its primary
      structure and fundamental biochemical characteristics. A cDNA clone encoding PIP
      was isolated from the liver total RNA by reverse transcriptase-polymerase chain
      reaction (RT-PCR). It contained a 603 bp open reading frame that encoded a 19
      residue signal sequence and a 182-residue protein. PIP showed about 60% sequence
      homology with those PLA(2) inhibitors having a urokinase-type plasminogen
      activator receptor-like domain structure. PIP was also functionally expressed as
      a fusion protein in Escherichia coli to explore its potential therapeutic
      significance. The recombinant PIP was shown to be identical to the native form in
      chromatographic behavior and biochemical characteristics. Both the native and
      recombinant PIP appear to exist as a hexamer of 23-kDa subunits having an
      apparent molecular mass of approximately 140 kDa. PIP showed ability to bind to
      the major PLA(2) toxin (daboiatoxin, DbTx) of Daboia russelli siamensis at 1-2
      fold molar excess of inhibitor to toxin. It exhibited broad spectra in
      neutralizing the toxicity of various snake venoms and toxins and inhibited the
      formation of edema in mice. Our data demonstrate the venom neutralizing potential
      of the recombinant PIP and suggest that the proline-rich hydrophobic core region
      may play a role in binding to PLA(2).

PMID- 10924160
TI  - Antitumor agents. 203. Carbazole alkaloid murrayaquinone A and related synthetic
      carbazolequinones as cytotoxic agents.
AB  - Murrayaquinone A (1) and murrayafoline A (3), isolated from the root bark of
      Murraya euchrestifolia, were identified as cytotoxic compounds. Murrayaquinone A
      (1) demonstrated significant cytotoxicity against SK-MEL-5 and Colo-205 cells,
      with ED(50) values of 2.58 and 3.85 microg/mL, respectively. In contrast,
      murrayafoline A (3) exhibited marginal or weak cytotoxicity against SK-MEL-5,
      Colo-205, HCT-8, KB, and A-549 tumor cell lines, with ED(50) values ranging from
      5.31 to 7.52 microg/mL. In total, 20 carbazole alkaloids (1-20), isolated
      previously by Furukawa et al. from various plant sources were also evaluated for
      their cytotoxic profiles in the NCI's human disease-oriented, 60-cell line, in
      vitro antitumor screening protocol. Compounds 3 and 15 showed potent cell-line
      selective cytotoxicity against MOLT-4 cells, with log GI(50) values of -8.60 and 
      8.49 M, respectively, while 12 demonstrated better selectivity against the colon
      cancer subpanel. Moreover, synthetic 2-methyl- or 3-methyl-carbazolequinone
      derivatives with various substituents in the A-ring were evaluated against KB, SK
      MEL-5, Colo-205, and HCT-8 tumor cells. 6-Methoxy- (21), 6-methyl- (22), and 6
      chloro- (24) 3-methyl-carbazolequinones demonstrated significant cytotoxicity
      against SK-MEL-5 cells, with ED(50) values of 0.55, 0.66, and 0.83 microg/mL,
      respectively. Compounds 21 and 22 were also significantly cytotoxic toward KB
      cells, with ED(50) values of 0.76 and 0.92 microg/mL, respectively, and 21
      displayed a similar level of toxicity against Colo-205 cells (ED(50) 0.87
      microg/mL).

PMID- 10924159
TI  - Dual structural requirements for multilineage hematopoietic-suppressive activity
      of chemokine-derived peptides.
AB  - Many chemokines have direct suppressive activity in vitro and in vivo on
      primitive hematopoietic cells. However, few chemokine-derived peptides have shown
      a significant activity in inhibiting hematopoiesis. Interestingly, a peptide
      derived from the 34-58 sequence of the CXC chemokine platelet factor 4 (PF4)
      produced a 30-40% inhibition of proliferation of murine hematopoietic progenitors
      (CFU-MK, CFU-GM, and BFU-E) in vitro, at concentrations of 30-60-fold lower than
      PF4. The aim of the present work was to define the structural parameters and
      motifs involved in conferring biological activity to the peptide PF4(34-58). Both
      structural predictions and determinations revealed a new helical motif that was
      further localized between residues 38 and 46. This helix was necessary for
      binding of the peptide and for permitting the functional DLQ motif at position 54
      56 to activate the putative receptor site. Peptides lacking either the helical or
      the DLQ motif were devoid of inhibitory activity on the hematopoietic progenitors
      in vitro. However, among inactive peptides, only those having the helical motif
      counteracted the inhibition induced by the active peptide PF4(34-58). This
      suggested that the helix might be required for peptide interactions with a
      putative receptor site, whereas the DLQ motif would be implicated in the
      activation of this receptor. These results identify for the first time the dual
      requirements for the design of chemokine-derived peptides with high suppressive
      activity on hematopoiesis, as well as for the design of molecules with
      antagonistic action.

PMID- 10924161
TI  - Taraxastane-type triterpenes from the aerial roots of Ficus microcarpa.
AB  - Seven new taraxastane-type triterpenes-20-taraxastene-3beta, 22alpha-diol (1),
      3beta-acetoxy-20-taraxasten-22alpha-ol (2), 3beta-acetoxy-22alpha-methoxy-20
      taraxastene (3), 3beta-acetoxy-20alpha,21alpha-epoxytaraxastan-22alp ha-ol (4),
      3beta-acetoxy-19alpha-methoxy-20-taraxastene (5), 3beta-acetoxy-19alpha
      hydroperoxy-20-taraxastene (6), 3beta-acetoxy-20alpha,21alpha-epoxytaraxastane
      (7)-were isolated from the aerial roots of Ficus microcarpa. Their structures
      were elucidated by spectroscopic and chemical methods.

PMID- 10924162
TI  - New caryophyllene derivatives from Betula litwinowii.
AB  - Four new caryophyllene derivatives-14-hydroxy-4, 5-dihydro-beta-caryophyllene
      (1), 14-acetoxy-4, 5-dihydro-beta-caryophyllene (2), 4, 5-dihydro-beta
      caryophyllene-14-al (3), and caryophylla-8(14)-en-5-one (4)-are reported from the
      essential oil of Betula litwinowii. Compounds 1-4 were characterized by MS and 1D
      and 2D NMR analyses and chemical transformations. The antibacterial and
      antifungal activity of 1 is also reported.

PMID- 10924163
TI  - Triterpene glycosides from Cimicifuga racemosa.
AB  - Eight new triterpene glycosides named cimiracemosides A-H, respectively, and
      eight known triterpene glycosides were isolated from the rhizome extracts of
      black cohosh (Cimicifuga racemosa). The new compounds were determined by spectral
      data to be 21-hydroxycimigenol-3-O-alpha-L-arabinopyranoside (1), 21
      hydroxycimigenol-3-O-beta-D-xylopyranoside (2), cimigenol-3-O-alpha-L
      arabinopyranoside (3), 12beta-acetoxycimigenol-3-O-alpha-L-arabinopyranoside (4),
      24-acetylisodahurinol-3-O-beta-D-xylopyranoside (5), 20(S),22(R), 23(S),24(R)
      16beta:23;22:25-diepoxy-12beta-acetoxy-3be ta,23, 24-trihydroxy-9,19-cycloanost-7
      ene-3-O-beta-D-xylopyranoside (6), 20(S),22(R),23(S),24(R)-16beta:23;22:25
      diepoxy-12beta -acetoxy-3beta, 23,24-trihydroxy-9,19-cycloanost-7-en-3-O-alpha-L
      arabinopyrano side (7), and 20(S),22(R),23(S), 24(R)-16beta:23;22:25-diepoxy
      12beta-acetoxy-3beta,23, 24-trihydroxy-9,19-cycloanostane-3-O-beta-D
      xylopyranoside (8).

PMID- 10924164
TI  - Thalicosides A1-A3, minor cycloartane bisdesmosides from Thalictrum minus.
AB  - Three new cycloartane bisdesmosides, two of which are based on a new genin, were
      isolated from the above-ground parts of Thalictrum minus. Thalicosides A1-A3 (1
      3) were characterized as 3-O-beta-D-galactopyranosyl-29-O-beta-D-glucopyranosyl
      3beta,16beta++ +, 29-trihydroxy-22(S),25-epoxycycloartane (1); 3-O-alpha-L
      arabinopyranosyl-29-O-beta-D-glucopyranosyl-3beta,1 6beta, 29,22(S)
      tetrahydroxycycloart-24-ene (2); and 3-O-alpha-L-arabinopyranosyl-29-O-beta-D
      glucopyranosyl-3beta,1 6beta, 29-trihydroxy-22(S),25-epoxycycloartane (3),
      respectively. The structural assignments of these new compounds were based on
      interpretation of spectroscopic data. Thalicoside A2 showed in vitro inhibition
      of the fungus Candida albicans and also activity against Staphylococcus aureus.

PMID- 10924165
TI  - New triterpenoid saponins from the sponge Melophlus isis.
AB  - Four new triterpenoid saponins were isolated, along with two known 30
      norlanostane-type saponins- sarasinosides A(1) (1) and A(3) (2)-from the sponge
      Melophlus isis collected from Guam. The structures of these new compounds (3-6)
      proved to be 30-norlanosta-8(14),24-dien-23-ones bearing two hydroxyl groups or
      the corresponding methoxy groups at the 9alpha,15alpha- and 9alpha, 15beta
      positions and the pentasaccharide portion identical with those of 1 and 2 at the
      3beta position, by spectral, chemical, and GC analyses.

PMID- 10924166
TI  - New natural product isolation and comparison of the secondary metabolite content
      of three distinct samples of the sea hare Aplysia dactylomela from tenerife.
AB  - Three distinct samples of the sea hare Aplysia dactylomela from two different
      locations around Tenerife (Spain) were investigated for their secondary
      metabolite content. The investigation resulted in the isolation of five new
      natural products (1, 2, 5-7), a number of compounds known from red algae of the
      genera Laurencia (4, 8-14) and Plocamium (17-19), and three known sea-hare
      metabolites (3, 15, 16). This is the first report of monoterpenes (17-19) from A.
      dactylomela. All structures were determined mainly by spectroscopic methods (1D
      and 2D NMR, MS, IR). Compounds 11, 14, 15, and 17 demonstrated significant
      cytotoxicity toward three cancer cell lines (HM02, HEP G2, and MCF 7; IC(50) for
      11, 7.0 to <1.0 microg/mL; 14, <1.0 microg/mL; 15, 17 to <1.0 microg/mL; 17, 1.0
      to 1.5 microg/mL). Compounds 3, 8, 9, 11, 15, 18, and 19 exhibited activity in a
      brine shrimp bioassay in the range of 100% lethality within 24 h to 40% after 48
      h. Metabolites 11, 14, 15, and 19 showed moderate antimicrobial activities (2-25
      mm total/growth inhibition of several organisms), with 19 also being strongly
      algicidal (MIC 7-11 microg/filter disk).

PMID- 10924167
TI  - New taxanes from the needles of Taxus canadensis.
AB  - Nine minor taxanes were identified for the first time in the Canadian yew
      needles. Four of these metabolites are new: 5-epi-cinnamoylcanadensene (1),
      2,9,10, 13-tetraacetoxy-20-cinnamoyloxy-taxa-4(5),11(12)-diene (2), 2'-acetyl-epi
      taxol (3), and 9-deacetyltaxinine E (4).

PMID- 10924168
TI  - Synthesis of (+/-)-11alpha-hydroxy-3-oxo-6alphaH,7alphaH, 10betaMe-eudesman-1,2
      4,5-dien-6,12-olide.
AB  - The synthesis of (+/-)-11alpha-hydroxy-3-oxo-6alphaH,7alphaH, 10betaMe-eudesman
      1,2-4,5-dien-6,12-olide (1), previously isolated from Melanoselinum decipiens, is
      described, and its structure has been corrected.

PMID- 10924169
TI  - Diterpenoids from the rhizomes of Alpinia calcarata.
AB  - Four new labdane-type diterpenoids, calcaratarins A-D (1-4), along with six known
      labdane-type diterpenoids, a known elemane-type sesquiterpenoid, and a known
      coumarin, were isolated from the rhizomes of Alpinia calcarata. The structures of
      1-4 were elucidated on the basis of spectroscopic studies.

PMID- 10924170
TI  - New isomalabaricane derivatives from a new species of Jaspis sponge collected at
      the Vanuatu islands.
AB  - Six new cytotoxic isomalabaricane-type triterpenoids and nortriterpenoids with a
      3alpha-acetoxy group were isolated, along with the known globostellatic acids B
      (1) and C (2), from the marine sponge Jaspis sp. collected at Vanuatu Island. The
      structures were determined by 2D NMR data and by comparison with spectral data of
      known related compounds.

PMID- 10924171
TI  - Tetranortriterpenoids from Walsura yunnanensis.
AB  - Five new tetranortriterpenoids-walsurin (1), isowalsuranolide (2), walsuranolide
      (3), 11beta-acetoxywalsuranolide (4), and 20, 22-dihydro-22,23-epoxywalsuranolide
      (5)-and three new natural tetranortriterpenoids-11beta-hydroxydihydrocedrelone
      (6), 11beta-acetoxydihydrocedrelone (7), and 11beta-hydroxycedrelone (8)-together
      with a known tetranortriterpenoid, cedrelone (9), were isolated from the bark of
      Walsura yunnanensis. The structures of 1-8 were determined on the basis of
      spectral evidence.

PMID- 10924172
TI  - Hermitamides A and B, toxic malyngamide-type natural products from the marine
      cyanobacterium Lyngbya majuscula.
AB  - A Papua New Guinea collection of the marine cyanobacterium Lyngbya majuscula
      yielded two new and toxic natural products, hermitamides A (1) and B (2). The
      hermitamides were isolated using a brine shrimp (Artemia salina) toxicity assay.
      Planar chemical structures of 1 and 2 were established through 1D and 2D NMR, as
      well as FABMS data. Semisyntheses of hermitamides A (1) and B (2) were achieved
      by coupling the acid chloride derivative of 7(S)-methoxytetradec-4(E)-enoic acid
      (4), obtained from the same cyanobacterium collection, and the respective free
      amines, phenethylamine and tryptamine. Hermitamides A (1) and B (2) exhibited
      LD(50) values of 5 microM and 18 microM in the brine shrimp bioassay, and an
      IC(50) values of 2.2 microM and 5.5 microM to Neuro-2a neuroblastoma cells in
      tissue culture, respectively. Hermitamide A was mildly ichthyotoxic to goldfish,
      with an LD(50) value of 19 microM, while hermitamide B was inactive at 25 microM.

PMID- 10924173
TI  - Haligramides A and B, two new cytotoxic hexapeptides from the marine sponge
      Haliclona nigra.
AB  - Bioassay-guided fractionation of a cytotoxic aqueous extract of the sponge
      Haliclona nigra provided two new cyclic hexapeptides, haligramides A (1) and B
      (2), in addition to the known peptide, waiakeamide (3). The structures of
      peptides 1 and 2 were elucidated by extensive NMR analyses and by comparison of
      their spectral data with those of waiakeamide (3). The identity of haligramide A
      (1) was confirmed by its oxidative conversion to waiakeamide (3). Further
      structural confirmation was provided by oxidation of peptides 1, 2, and 3 to the
      common bis-sulfone derivative 4.

PMID- 10924174
TI  - Isolation of stereoisomeric epoxy carotenoids and new acetylenic carotenoid from
      the common freshwater goby Rhinogobius brunneus.
AB  - Stereoisomeric epoxy carotenoids with 3,5-cis configuration, diadinoxanthin B
      [(3S,5S,6R,3'R)-diadinoxanthin] (1) and antheraxanthin B [(3S,5S,6R,3'R)
      antheraxanthin] (2), along with diadinoxanthin A [(3S,5R,6S,3'R)-diadinoxanthin]
      and antheraxanthin A [(3S,5R,6S,3'R)-antheraxanthin], were isolated from the
      common freshwater goby Rhinogobius brunneus. This is the first example in nature
      of 3,5-cis carotenoid epoxides. Furthermore, a new acetylenic triol carotenoid,
      gobiusxanthin (3), was obtained, and its structure was determined to be 7,8
      didehydro-beta, epsilon-carotene-3,3', 6'-triol by chemical and spectral data.

PMID- 10924175
TI  - Two new malyngamides from a Madagascan Lyngbya majuscula.
AB  - The lipid extract of a Madagascan Lyngbya majuscula has yielded malyngamides Q
      and R, both amides of 7-methoxytetradec-4-enoic acid. The isolation of these
      metabolites was accomplished using preparative liquid chromatography, with final
      purification through repetitive reversed-phase HPLC. Structure elucidation was
      accomplished utilizing 1D and 2D NMR spectroscopic characterization of the
      natural products and comparisons with malyngamides A and B. DPFGSE 1D NOE data
      suggested a different geometrical stereochemistry at C-6 in malyngamides Q and R
      from that observed for malyngamide A, as well as the other known malyngamides.
      The Z stereochemistry was confirmed for malyngamide R by measurement of key
      diagnostic (3)J(CH) couplings utilizing the HSQMBC pulse sequence. The absolute
      stereochemistry of C-4' ' of the pyrrolidone ring was defined by chiral GCMS
      analysis of serine released by ozonolysis and acid hydrolysis.

PMID- 10924176
TI  - Antineoplastic agents 440. Asymmetric synthesis and evaluation of the
      combretastatin A-1 SAR probes (1S,2S)- and (1R,2R)-1, 2-dihydroxy- 1-(2',3'
      dihydroxy-4'-methoxyphenyl)-2-(3' ',4' ',5' '-trimethoxyphenyl)-ethane.
AB  - The synthetic (E)-isomer (3b) of natural combretastatin A-1 (1a) isolated from
      the African bushwillow Combretum caffrum was the focus of chiral hydroxylation
      (Sharpless) reactions as part of a structure-activity relationship study. The
      resulting (R,R)- and (S,S, )-diols (6 and 7) and synthetic intermediates were
      evaluated against a series of cancer cell lines, microorganisms, and tubulin.
      Chiral diols 6 and 7 showed increased activity against the P-388 murine
      lymphocytic leukemia cell line with ED(50) values of 3.9 and 2.9 microg/mL,
      respectively, when compared to the precursor (E)-stilbene 3b. In contrast, (E)
      stilbene 3b exhibited more potent antibiotic activity than the chiral diols (6
      and 7). Both diols, (R,R)-6 and (S, S)-7, displayed less cancer cell growth
      inhibition and less antibiotic activity than did natural combretastatin A-1 (1a)
      (P-388 ED(50) 0.25 microg/mL).

PMID- 10924177
TI  - New variotin analogues from Aspergillus viridi-nutans.
AB  - Besides the antifungal agents variotin (1), wasabidienone B(0) (4), and
      phomaligin A (5), two new but inactive metabolites, viriditin (2) and O
      methylviriditin (3), were isolated from extracts of the culture filtrate of
      liquid cultures of a strain of Aspergillus viridi-nutans. In addition,
      wasabidienone B(1) (6) was isolated and characterized by spectroscopy.

PMID- 10924178
TI  - (2R,3R,7Z)-2-Aminotetradec-7-ene-1,3-diol, a new amino alcohol from the caribbean
      sponge Haliclona vansoesti.
AB  - The Caribbean marine sponge Haliclona vansoesti was found to contain a high
      amount (5% dry wt) of a new analogue of 4-sphingenine, (2R,3R, 7Z)-2
      aminotetradec-7-ene-1,3-diol (1). Its structure was determined by detailed
      spectroscopic analysis. The relative configuration was deduced from the NMR data
      of the corresponding acetonide 5, while the absolute configuration was secured
      via protection of the primary alcohol and amino groups, and esterification of the
      secondary alcohol with Mosher's reagent.

PMID- 10924179
TI  - Matemone, a new bioactive bromine-containing oxindole alkaloid from the indian
      ocean sponge Iotrochota purpurea.
AB  - A new bioactive bromine-containing oxindole alkaloid, matemone (1), was isolated
      from the Indian Ocean sponge Iotrochota purpurea, together with the known 6
      bromoindole-3-carbaldehyde. The structures were elucidated on the basis of
      spectral and chemical data. Compound 1 shows mild cytotoxicity against three
      cancer cell lines and marginal antibacterial activity against Staphyloccocus
      aureus. DNA intercalant screening demonstrated DNA interactions with 1. Both
      compounds inhibit division of sea-urchin eggs.

PMID- 10924181
TI  - Sileneoside H, a new phytoecdysteroid from Silene brahuica.
AB  - Sileneoside H (1), a new phytoecdysteroid, has been isolated from the roots of
      Silene brahuica and identified as 22-O-alpha-D-galactosylintegristerone A 25
      acetate by MS and NMR analysis.

PMID- 10924180
TI  - New macrolactins from a marine Bacillus sp. Sc026.
AB  - Bioassay-guided fractionation of the EtOAc extract of a marine Bacillus sp. Sc026
      culture broth has led to the isolation of the known compound, macrolactin F (1),
      together with two new compounds, 7-O-succinyl macrolactin F (2) and 7-O-succinyl
      macrolactin A (3). The chemical structures of 1-3 were elucidated on the basis of
      spectral data analyses and literature data comparison. Compounds 1-3 exhibited
      antibacterial activity against Bacillus subtilis and Staphylococcus aureus.

PMID- 10924182
TI  - Highly oxygenated monoterpenes from Chenopodium ambrosioides.
AB  - Three new monoterpenes (3-5) were isolated from an organic extract of the aerial
      parts of Chenopodium ambrosioides. Structures were established on the basis of MS
      and NMR spectroscopic ((1)H, (13)C, (1)H-(1)H COSY, HMQC and HMBC) data.

PMID- 10924183
TI  - Glycals in the stereoselective synthesis of triterpene 2-deoxy-alpha-L-glycosides
      under conditions of acidic catalysis.
AB  - 3beta-Hydroxy triterpenes of the oleanane, ursane, and lupane types were
      successfully glycosylated with acetylated L-glucal and L-rhamnal under conditions
      of acidic catalysis (anhydrous cation-exchange resin and LiBr). The 2-deoxy- and
      2, 6-dideoxy-alpha-L-arabino-hexopyranosides (1-5) were stereoselectively
      prepared in 83-90% yields, following deacetylation under mild conditions, which
      led to the target triterpene 2-deoxy-alpha-L-glycosides (6-10).

PMID- 10924184
TI  - New quinoline alkaloids from Ruta chalepensis.
AB  - The roots of Ruta chalepensis, collected from the northern Saudi desert, yielded
      two new quinoline alkaloids, namely, 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '
      yl)hexyl?-hydroquinolin-4-one (1) and 2-?6'-(2H-benzo[d]1' ',3' '-dioxolen-5' '
      yl)hexyl?-4-methoxy-quinoline (2). Nine previously reported alkaloids,
      dictamnine, pteleine, skimmianine, rutacridone, isogravacridonechlorine,
      maculosidine, graveoline, graveolinine, and 4-methoxy-1-methyl-2(1H)-quinolinone,
      and coumarins, chalepensin, and umbelliferone were also isolated. Structure
      elucidations were based primarily on 1D and 2D NMR analyses and chemical
      transformations. Antimicrobial activity of these compounds is discussed.

PMID- 10924185
TI  - Bis-iridoid glucosides from Abelia chinensis.
AB  - Seven bis-iridoid glucosides have been isolated from Abelia chinensis and were
      characterized by having a secoiridoid residue as unit A esterifying a C(10)
      iridoid or a delta-lactone iridoid as unit B. Among these, compounds 1-3 are new
      and correspond to 7-O-acetyllaciniatoside IV, 7-O-acetyllaciniatoside V, and 7-O
      acetylabelioside B, respectively. The structures of 1-3 were elucidated by
      spectral methods.

PMID- 10924187
TI  - The structure of sarcomejine: an application of long-range (1)H-(15)N correlation
      at natural abundance.
AB  - A new 4(1H)-quinolinone alkaloid, sarcomejine (1), has been isolated from the
      bark of Sarcomelicope megistophylla. Its structure has been elucidated on the
      basis of MS and NMR data and especially with a long-range (1)H-(15)N correlation
      NMR spectrum at natural abundance.

PMID- 10924186
TI  - ent-kaurane diterpenoids from Annona glabra.
AB  - Three new kaurane diterpenoids, annoglabasin C (16alpha-acetoxy-ent-kauran-19-oic
      acid-17-methyl ester) (1), annoglabasin D (16alpha-acetoxy-ent-kauran-19-al-17
      methyl ester) (2), and annoglabasin E (16alpha-hydro-19-ol-ent-kauran-17-oic
      acid) (3), and a new norkaurane diterpenoid, annoglabasin F (16alpha-acetoxy-19
      nor-ent-kauran-4alpha-ol-17-methyl ester) (4), along with 13 known kaurane
      derivatives were isolated from the stems of Annona glabra. 16alpha-Methoxy-ent
      kauran-19-oic acid (5) and 16alpha-hydro-ent-kauran-17,19-dimethyl ester (6) were
      obtained for the first time as natural products. The structures of compounds 1-6
      were characterized by spectral analysis.

PMID- 10924188
TI  - New cyclic peptide and bisindolyl benzenoid metabolites from the sclerotia of
      Aspergillus sclerotiorum.
AB  - Scleramide (1), a new cyclic hexapeptide, and a new oxidized bisindolyl benzenoid
      derivative (2' '-oxoasterriquinol D methyl ether, 2) were isolated from extracts
      of the sclerotia of Aspergillus sclerotiorum (NRRL 5167). The structures of these
      compounds were determined by analysis of 1D and 2D NMR experiments.

PMID- 10924189
TI  - Taraxacin, a new guaianolide from Taraxacum wallichii.
AB  - A new guaianolide, taraxacin (1), and a known sesquiterpene ketolactone (2) have
      been isolated from an ethyl acetate-soluble part of a methanolic extract of
      Taraxacum wallichii. The structure of 1 was established using NMR, MS, and X-ray
      crystallographic methods. The (13)C NMR data of 2 is also being reported for the
      first time.

PMID- 10924190
TI  - Rivalosides A and B, two 19-Oxo triterpenoid saponins from Galium rivale.
AB  - Two new oleanene-type triterpene glycosides, rivaloside A (2alpha-acetoxy-3alpha
      hydroxy-19-oxo-olean-12-en-28-o ic acid 28-O-beta-glucopyranosyl-(1-->6)-beta-D
      glucopyranoside) (1) and rivaloside B (2alpha,3alpha-dihydroxy-19-oxo-olean-12-en
      28-oic acid 28-O-beta-glucopyranosyl-(1-->6)-beta-D-glucopyranoside) (2), were
      isolated from aerial parts of Galium rivale. The structures were determined on
      the basis of spectroscopic data and chemical transformations. Under alkaline or
      acid hydrolysis, rivalosides A and B undergo allylic rearrangement with migration
      of the double bond. These compounds are the first representatives of 19-oxo
      substituted oleanenes, and they seem to be promising as taxonomic markers for G.
      rivale.

PMID- 10924191
TI  - New rearranged limonoids from Harrisonia perforata.
AB  - Two new rearranged limonoids, named haperforine A (1) and haperforine E (2), were
      isolated from a sample of Harrisonia perforata leaves collected in Center Vietnam
      and their structures determined by X-ray diffraction analysis. The structure of a
      minor compound was established as 12-desacetylhaperforine A (3) by chemical
      correlation. Their NMR and mass spectroscopic properties are reported.

PMID- 10924192
TI  - Hepatoprotective diastereomeric lignans from Saururus chinensis herbs.
AB  - Two new diastereomeric sauchinones (2, 3), along with the known sauchinone (1), a
      phenylpropanoid (sarisan), and two known lignans (galbacin and saucernetin), were
      isolated from the n-hexane fraction of Saururus chinensis using reversed-phase
      HPLC. The stereostructures of the lignans, sauchinone A (2) and 1'-epi-sauchinone
      (3), were established by analysis of spectroscopic data. Incubation of cultured
      rat hepatocytes intentionally injured by CCl(4) with each of the compounds 1, 2,
      and 3 significantly reduced the levels of glutamic pyruvic transaminase released
      by the damaged hepatocytes.

PMID- 10924193
TI  - Two complex proline esters from the sea hare Stylocheilus longicauda.
AB  - Investigation of Stylocheilus longicauda led to the isolation of chlorinated
      metabolites, makalika ester (1) and makalikone ester (2). Also reported is the
      isolation of lyngbyatoxin A acetate (3). The structures of the new compounds are
      based on spectroscopic data obtained from 1D and 2D NMR experiments.

PMID- 10924194
TI  - Phenalenones from Strelitzia reginae.
AB  - Phytochemical analysis of rhizomes of Strelitzia reginae resulted in the
      isolation and identification of an unusual new (1) and four known phenalenone
      type compounds, which were identified using MS and NMR spectroscopic techniques.
      The occurrence of phenalenones in Strelitziaceae, which has been established for
      the first time, is of chemotaxonomic interest.

PMID- 10924195
TI  - Neoclerodane diterpenoids from Teucrium maghrebinum.
AB  - Eight neoclerodane diterpenoids were identified in the extract of the aerial
      parts of Teucrium maghrebinum. Three of these, 12-epi-teucjaponin A (1), 12-epi
      montanin D (2), and 12-epi-montanin B (3), are new natural products, whereas
      five, teucjaponin A, montanin D, 19-deacetylteuscorodol, teusalvin C (4), and
      montanin B, are already known. These eight compounds form four pairs of epimers
      at carbon C-12.

PMID- 10924196
TI  - Minor diterpenoids from Scutellaria polyodon.
AB  - Four minor neoclerodane diterpene constituents were isolated from the aerial
      parts of Scutellaria polyodon. These compounds were characterized as the new
      scupolins J (1) and K (2) and the previously known scutalpin O (3) and scutalsin.

PMID- 10924197
TI  - Flavonoids as antioxidants.
AB  - Flavonoids are phenolic substances isolated from a wide range of vascular plants,
      with over 8000 individual compounds known. They act in plants as antioxidants,
      antimicrobials, photoreceptors, visual attractors, feeding repellants, and for
      light screening. Many studies have suggested that flavonoids exhibit biological
      activities, including antiallergenic, antiviral, antiinflammatory, and
      vasodilating actions. However, most interest has been devoted to the antioxidant
      activity of flavonoids, which is due to their ability to reduce free radical
      formation and to scavenge free radicals. The capacity of flavonoids to act as
      antioxidants in vitro has been the subject of several studies in the past years,
      and important structure-activity relationships of the antioxidant activity have
      been established. The antioxidant efficacy of flavonoids in vivo is less
      documented, presumably because of the limited knowledge on their uptake in
      humans. Most ingested flavonoids are extensively degraded to various phenolic
      acids, some of which still possess a radical-scavenging ability. Both the
      absorbed flavonoids and their metabolites may display an in vivo antioxidant
      activity, which is evidenced experimentally by the increase of the plasma
      antioxidant status, the sparing effect on vitamin E of erythrocyte membranes and
      low-density lipoproteins, and the preservation of erythrocyte membrane
      polyunsaturated fatty acids. This review presents the current knowledge on
      structural aspects and in vitro antioxidant capacity of most common flavonoids as
      well as in vivo antioxidant activity and effects on endogenous antioxidants.

PMID- 10924198
TI  - The different roles of social learning in vocal communication.
AB  - While vocal learning has been studied extensively in birds and mammals, little
      effort has been made to define what exactly constitutes vocal learning and to
      classify the forms that it may take. We present such a theoretical framework for
      the study of social learning in vocal communication. We define different forms of
      social learning that affect communication and discuss the required methodology to
      show each one. We distinguish between contextual and production learning in
      animal communication. Contextual learning affects the behavioural context or
      serial position of a signal. It can affect both usage and comprehension.
      Production learning refers to instances where the signals themselves are modified
      in form as a result of experience with those of other individuals. Vocal learning
      is defined as production learning in the vocal domain. It can affect one or more
      of three systems: the respiratory, phonatory and filter systems. Each involves a
      different level of control over the sound production apparatus. We hypothesize
      that contextual learning and respiratory production learning preceded the
      evolution of phonatory and filter production learning. Each form of learning
      potentially increases the complexity of a communication system. We also found
      that unexpected genetic or environmental factors can have considerable effects on
      vocal behaviour in birds and mammals and are often more likely to cause changes
      or differences in vocalizations than investigators may assume. Finally, we
      discuss how production learning is used in innovation and invention, and present
      important future research questions. Copyright 2000 The Association for the Study
      of Animal Behaviour.

PMID- 10924199
TI  - Acoustics, context and function of vibrational signalling in a lycaenid butterfly
      ant mutualism.
AB  - Juveniles of the Australian common imperial blue butterfly, Jalmenus evagoras,
      produce substrate-borne vibrational signals in the form of two kinds of pupal
      calls and three larval calls. Pupae stridulate in the presence of conspecific
      larvae, when attended by an ant guard, and as a reaction against perturbation.
      Using pupal pairs in which one member was experimentally muted, pupal calls were
      shown to be important in ant attraction and the maintenance of an ant guard. A
      pupa may use calls to regulate levels of its attendant ants and to signal its
      potential value in these mutualistic interactions. Therefore substrate-borne
      vibrations play a significant role in the communication between J. evagoras and
      its attendant ants and pupal calls appear to be more than just signals acting as
      a predator deterrent. Similarly, caterpillars make more sound when attended by
      Iridomyrmex anceps, suggesting that larval calls may be important in mediating
      ant symbioses. One larval call has the same mean dominant frequency, pulse rate,
      bandwidth and pulse length as the primary signal of a pupa, suggesting a
      similarity in function. Copyright 2000 The Association for the Study of Animal
      Behaviour.

PMID- 10924200
TI  - Sex identification and mating in the blue-ringed octopus, Hapalochlaena lunulata.
AB  - We studied the reproductive behaviour of the blue-ringed octopus, Hapalochlaena
      lunulata, in the laboratory by examining 15 male-male and nine male-female
      interactions. The initiation of physical contact was independent of sex, size or
      residency status, and there were no noticeable changes in behaviour such as
      sexual displays associated with courtship or aggression prior to contact. Males
      did not distinguish between females or other males and copulated (defined as the
      insertion of the hectocotylus into the mantle cavity of another octopus) readily
      with both. Spermatophores were released in all copulations with females but not
      with males. The duration of copulation was significantly longer in male-female
      interactions (median 160.5 min) than in male-male interactions (median 30 s).
      Although male-male copulations ended passively with the withdrawal of the
      hectocotylus by the initiating animal, male-female copulations were always
      terminated by the females following an intense struggle. These studies suggest
      the inability of male H. lunulata to determine the sexual identity of potential
      mates prior to the insertion of the hectocotylus and demonstrate the active role
      of the female during copulation. Copyright 2000 The Association for the Study of
      Animal Behaviour.

PMID- 10924201
TI  - Testing the interspecific body size principle in ungulates: the smaller they
      come, the harder they groom.
AB  - Tick removal grooming may be centrally regulated by an internal timing mechanism
      operating to remove ticks before they attach and engorge (programmed grooming
      model) and/or evoked by cutaneous stimulation from tick bites (stimulus-driven
      model). The programmed grooming model predicts that organismic and environmental
      factors that impact the cost-benefit ratio of grooming (e.g. body size and
      habitat) will influence the rate of tick removal grooming. The body size
      principle predicts that smaller-sized animals, because of their greater surface
      to-mass ratio, should engage in more frequent tick removal grooming than larger
      bodied animals in order to compensate for higher costs of tick infestation. The
      body size principle may be tested intraspecifically between young and adult
      animals, or interspecifically among species of contrasting body sizes. To
      rigorously test the interspecific body size prediction, we observed the
      programmed grooming (oral and scratch grooming) of 25 species (or subspecies) of
      bovids at a tick-free zoological park in which stimulus-driven grooming was ruled
      out. Multiple correlation analysis revealed highly significant negative
      correlations between species-typical mass and mean species grooming rates when
      habitat was controlled for in the model. Species-typical habitat type (classified
      along a gradient from most open to most closed) was positively correlated with
      mean oral grooming rate, indicating that species tended to groom at a higher rate
      in woodland and forest habitats (where typical tick density would be high)
      compared with more open environments. Species mass accounted for up to two-thirds
      of the variation in grooming rate across species, whereas habitat accounted for
      ca. 20% of variation in oral grooming. Similar results were obtained when the
      analysis was expanded to include 36 species/subspecies of six different families.
      The body size principle can therefore account for a large proportion of species
      typical differences in programmed grooming rate among ungulates. However, to
      understand the tick defence adaptations of very large mammals that rarely or
      never engage in oral or scratch grooming (e.g. elephants, giraffes, rhinoceros),
      alternative tick defence strategies must be considered, such as thick skin,
      wallowing, rubbing and tolerance of oxpeckers and other tick-eating birds.
      Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924202
TI  - Removal of adult males from the rearing environment increases preference for same
      sex partners in the zebra finch.
AB  - The developmental processes producing preferences for opposite-sex mating
      partners are not well understood. Zebra finches, Taeniopygia guttata, are
      colonial and socially monogamous with biparental care. To determine whether the
      early social environment contributes to sexual partner preference, we removed
      adult males from breeding colonies when the oldest chicks were less than 1 week
      old (male-removal rearing) or left them in the breeding cage (control rearing).
      At independence, male-removal and control offspring were moved to unisex cages.
      As adults they were given two-choice tests with male versus female stimuli
      followed by group aviary tests. Male-removal subjects, unlike controls, did not
      prefer opposite-sex stimuli in the two-choice tests. Male-removal subjects were
      less likely than controls to successfully pair with opposite-sex birds in the
      group aviary tests; 38% of them paired with a same-sex bird. Thus early social
      experience may contribute to a critical component of mate choice, choosing the
      opposite sex, in this pair-bonding species. Copyright 2000 The Association for
      the Study of Animal Behaviour.

PMID- 10924203
TI  - Division of labour in colony defence against vertebrate predators by the social
      wasp Polistes fuscatus.
AB  - In this study I examined how the paper wasp, Polistes fuscatus, defends a colony
      when faced with a vertebrate attack. I looked for a division of labour in
      defensive behaviour within a colony and examined whether this behaviour changes
      over the colony cycle. The colonies were presented with a model of an adult red
      winged blackbird, Agelaius phoeniceus, and a speaker that vibrated the comb.
      There was a pronounced division of labour in the defence against vertebrate
      predators within a colony. The queen was consistently the most aggressive
      individual in the colony. The subordinate foundresses and workers both became
      more aggressive towards a vertebrate predator as they aged. Gynes and males did
      not participate in colony defence. The level of aggression in colony members of
      P. fuscatus appears to be related to the reproductive investment of the colony.
      Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924204
TI  - Habituation and development of response specificity to a sign stimulus: male
      preference for female courtship posture in stickleback.
AB  - I examined biased patterns of habituation that occur when reproductive male three
      spined stickleback, Gasterosteus aculeatus, respond to a choice of two dummy
      females, one displaying the head-up posture of a sexually receptive female and an
      otherwise identical dummy lacking this sign stimulus (i.e. a dummy in a 'neutral'
      horizontal posture). Males initially courted both dummies about equally, but
      within 5 min, their courtship to the horizontal dummy began to habituate and was
      eventually replaced by attack behaviour, which increased about four-fold during
      the 1-h trial. Courtship to the head-up dummy continued unabated throughout the
      trial and by 5 min exceeded courtship to the horizontal dummy. Attack to the head
      up dummy increased slightly in the first half of the trial then leveled off to
      about one-third that directed to the horizontal dummy. Both dummies were
      stationary and unreactive so could not directly provide differential feedback to
      the males. It is speculated that the self-arousal males obtain when responding to
      head-up posture reinforces their response to that cue. The salience of this sign
      stimulus may develop through an interactive process wherein the male's
      predisposition to recognize and court the head-up posture and the sexual self
      arousal he obtains by doing so counter habituation and help maintain his sexual
      response to that cue. The stimulus-response specificity of male courtship is
      assumed to have an innate basis but requires experience to become fully
      differentiated. The results also illustrate that rate or extent of habituation to
      different stimuli, even on the same dimension, can differ within the same
      individual and in an adaptive manner. Copyright 2000 The Association for the
      Study of Animal Behaviour.

PMID- 10924205
TI  - Seeing group members eating a familiar food enhances the acceptance of novel
      foods in capuchin monkeys.
AB  - In primates, social context is one of the factors that increases the acceptance
      of novel foods. Previous experiments showed that tufted capuchins, Cebus apella,
      eat significantly more of novel foods when in the presence of group members
      eating the same novel foods. Several processes may have led to these results. The
      mere presence of group members may reduce the individual's stress of being alone,
      or its neophobic response and, consequently, may increase its food consumption.
      The individual may be influenced by what group members do, and local/stimulus
      enhancement and/or social facilitation may occur. To investigate the above
      processes, we assessed whether an individual capuchin monkey's consumption of
      novel foods is lower when (1) the individual is alone with nobody in the nearby
      cage than when (2) group members are present in the nearby cage with no food or
      when (3) they are present and eating a familiar food. We tested 15 subjects with
      three novel foods, each presented in one condition. In both social conditions,
      the more group members there were by the food box the more the experimental
      subject ate. In addition, when group members were present and eating food, there
      was a significant increase in the acceptance of the three foods, regardless of
      what group members were eating. We argue that social facilitation of eating is a
      quicker way to overcome neophobia and only social facilitation of eating what the
      others are eating can be considered a safe way to learn about a safe diet.
      Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924206
TI  - Colony sound facilitates sexual and agonistic activities in royal penguins.
AB  - A unique playback system was used to exaggerate continuously the number of calls
      heard in royal penguin, Eudyptes schlegeli, colonies to determine whether social
      facilitation increases a female's exposure to both sexual and agonistic
      activities, a process that could influence the timing of reproduction in
      colonies. We also determined whether the source of colony sound or the phase of
      the breeding cycle influenced the facilitation of sexual or agonistic activities.
      The system recorded and then played a new 12-min colony sound sample every 24 min
      throughout the first four phases of the breeding cycle. Because each broadcast
      was unique, this playback system avoids the possibility of habituation and can
      modify the acoustic environment in social groups for extended periods of time.
      The activities of penguins in control colonies (with no playback) were compared
      with those in colonies that heard samples derived from either their own or a
      different colony. Colony sound facilitated both sexual and agonistic activities
      from male and female royal penguins during all four phases of the cycle that we
      examined. Playbacks from the perceiver's own colony facilitated a greater
      response than sound originating from a different colony. Studies comparing egg
      laying dates in colonies exposed continuously to the sounds of agonistic
      activities with those in control colonies, or colonies exposed continuously to
      the sounds of sexual activities are now needed to determine whether the
      facilitation of agonistic activities opposes the effects of social stimulation on
      the hormonal changes leading to ovulation in colony-dwelling birds. Copyright
      2000 The Association for the Study of Animal Behaviour.

PMID- 10924207
TI  - Dynamics of intersexual conflict over precopulatory mate guarding in two
      populations of the isopod Idotea baltica.
AB  - Aggressiveness during intersexual conflicts is predicted to depend on its costs,
      the value of winning and the power asymmetry of the contestants, all of which may
      vary between populations. In the marine isopod Idotea baltica (Pallas) a conflict
      occurs as females resist the attempts by males to start precopulatory mate
      guarding. We analysed contest dynamics with respect to female maturity stage,
      that is, to time left to reproductive moult, with which the payoffs of guarding
      for males and females change. We did this in two populations that differ in
      synchrony of reproduction, sex ratio and the degree of sexual dimorphism. The
      intensity and dynamics of contests differed between populations: in the more size
      dimorphic population, females, the smaller sex, resisted less by forceful flexing
      but more by hooking their body than in the other population. Male aggressiveness
      stayed at a constant level with respect to female maturity. In the less size
      dimorphic population, female resistance by flexing was intense and it decreased,
      while male persistence increased, with the approaching reproductive moult.
      Contests were more intense with small than with large males. These results fit
      well with the predictions from models of conflict behaviour. Assessment of the
      payoffs of winning versus contest costs, coadaptation of the level of
      aggressiveness to the other traits affecting contest outcome, and
      counteradaptations by the sexes to each other largely explain the dynamics and
      between-population differences of these contests. Copyright 2000 The Association
      for the Study of Animal Behaviour.

PMID- 10924208
TI  - Decision time and prey gregariousness influence attack probability in naive and
      experienced predators.
AB  - Aposematic coloration often has an element of conspicuousness. One suggested
      benefit of conspicuousness is that it enables the prey to be detected at a
      greater distance, allowing a predator more time to make a correct decision about
      attacking it and thus reducing possible recognition errors made by predators. I
      conducted an experiment, with chicks, Gallus gallus domesticus, as predators on
      live aposematic and nonaposematic prey, to investigate the effects of decision
      time and signal size on predator sampling behaviour. The chicks were subjected to
      different degrees of competition to influence how quickly decisions had to be
      made. Chicks in four treatment groups, either in the presence or absence of a
      competing chick, were presented with either solitary prey or prey in groups. In
      the presence of a competitor, chicks attacked the prey more often and more
      quickly and needed more attacks before they started to avoid the prey. With prey
      in groups, chicks took longer to attack, attacked less often, learnt to avoid
      prey more quickly and killed fewer aposematic prey. This experiment provides
      evidence for the importance of time and signal size for predators' attack
      decisions. More time to view prey prior to attack could produce a stronger image
      and thus encourage avoidance learning and produce a stronger neophobic avoidance
      effect. Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924209
TI  - Male wrens with large testes breed early.
AB  - To display to females, male wrens, Troglodytes troglodytes, use cock nests built
      on their territories. Nest building starts about a month before the first females
      begin egg laying. The timing of nest building is highly variable between males
      with up to 8 weeks separating the earliest from the latest males to initiate this
      display activity. Males that weigh more before the breeding season initiate nest
      building earlier than lighter males. We measured testis size in male wrens in the
      prebreeding period during which seasonal testicular recrudescence is occurring.
      The initiation of nest building was predicted by male age and by testis size.
      This suggests that variation in the start of courtship activity may reflect
      variation between males in the rate of testicular recrudescence. Variation in
      male prebreeding body mass was influenced by variation in testis size, which
      suggests that the relation reported earlier between body mass and timing of nest
      construction could be explained, in part, by variation in testis size.
      Alternatively, if body mass reflects body condition then both the extent of
      testes recrudescence and the timing of courtship activity could be condition
      dependent traits. Copyright 2000 The Association for the Study of Animal
      Behaviour.

PMID- 10924210
TI  - Use and function of genital contacts among female bonobos.
AB  - Female bonobos, Pan paniscus, show a mounting behaviour that differs physically
      from that in other primate species. They embrace each other ventroventrally and
      rub their genital swellings against each other. We investigated five hypotheses
      on the function of ventroventral mounting (genital contacts) that derive from
      previous studies of both primate and nonprimate species: (1) reconciliation; (2)
      mate attraction; (3) tension regulation; (4) expression of social status; and (5)
      social bonding. We collected data in six field seasons (1993-1998) from members
      of a habituated, unprovisioned community of wild bonobos at Lomako, Democratic
      Republic of Congo. No single hypothesis could account for the use of genital
      contacts, which appeared to be multifunctional. We found support for hypotheses 1
      and 3. Rates of postconflict genital contacts exceeded preconflict rates
      suggesting that the display is used in the context of reconciliation. Rates of
      genital contacts were high when food could be monopolized and tension was high.
      However, genital contacts also occurred independently of agonistic encounters.
      Our study shows rank-related asymmetries in initiation and performance of genital
      contacts supporting the social status hypothesis: low-ranking females solicited
      genital contacts more often than high-ranking females while the latter were more
      often mounter than mountee. Although subordinates took more initiative to achieve
      genital contact, dominants mostly responded to the solicitation (ventral
      presentation) with mounting, indicating that the performance benefits both
      individuals. We suggest that genital contacts can be used to investigate both
      quality and dynamics of dyadic social relationships among female bonobos.
      Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924211
TI  - Predator avoidance, breeding experience and reproductive success in endangered
      cheetahs, Acinonyx jubatus.
AB  - I examine three hypotheses about predator avoidance behaviour: (1) avoidance
      increases an individual's reproductive success; (2) avoidance changes with
      breeding experience according to one of three described models; and (3) any
      reproductive or experience benefits accrued to individuals by avoidance are
      reflected in their spatial distribution. These hypotheses were tested on cheetahs
      which incur substantial juvenile mortality from predation by two larger
      competitors: spotted hyaenas, Crocuta crocuta, and lions, Panthera leo. To
      examine avoidance tactics, I played lion and hyaena vocalizations to individual
      female cheetahs. Lion avoidance increased with the statistical interaction
      between age and reproductive success, suggesting that it may be a learned
      behaviour, reinforced by successful reproductive events. This behaviour
      translated into a nonrandom spatial distribution of cheetahs with the most
      reproductively successful females found near lower lion densities than less
      successful females. Hyaena avoidance decreased with the interaction between age
      and reproductive success, suggesting that it is diminished by successful
      reproductive events, perhaps because a female cheetah switches from avoidance to
      using antipredator behaviours as she gets older. Hyaena avoidance behaviour
      translated into a spatial distribution with the most reproductively successful
      females found near lower hyaena densities than less successful females; however,
      younger females were found near lower hyaena densities than older females.
      Copyright 2000 The Association for the Study of Animal Behaviour.

PMID- 10924212
TI  - Individual differences in the use of social information in foraging by captive
      great tits.
AB  - We investigated individual differences in copying behaviour of captive great
      tits, Parus major, by analysing their response to a tutor indicating a new
      feeding site. We used two groups, each of seven male birds, labelled 'fast' and
      'slow' explorers based on previous studies in which consistent individual
      differences in the speed of exploring were found. The birds were trained to
      search for food hidden in a number of differently coloured and shaped feeders,
      and later to search in only one type of feeder. During the tests, food was absent
      and the birds were observed in two different situations: alone or in the presence
      of a tutor, a bird that had been trained to feed in a different kind of feeder.
      When alone, slow birds readily extended their search to other feeders while fast
      birds did not change their routine of visiting the previously rewarded ones. In
      the presence of the tutor, the opposite occurred: slow birds did not change their
      behaviour while fast birds significantly increased their visits to the feeders
      indicated by the tutor. Fast and slow individuals thus differ in their foraging
      and copying behaviour, consistent with the producer-scrounger model. Copyright
      2000 The Association for the Study of Animal Behaviour.

PMID- 10924213
TI  - Initial evolution of warning coloration: comments on the novel world method.

PMID- 10924214
TI  - Patterns of comprehension and production of nouns and verbs in agrammatism:
      implications for lexical organization.
AB  - This study examined the relationship between verb retrieval and verb-argument
      structure properties in seven agrammatic aphasic patients using tasks requiring
      access to the verb's lexicon for both comprehension- and productionlike
      processes. Results showed intact comprehension of both nouns and verbs and noun
      naming, but impaired naming of verbs. Subjects also demonstrated near-normal
      performance on a grammaticality judgment task involving verb-argument-structure
      violations but were impaired in categorizing verbs by type (based on number of
      obligatory arguments). In both naming and categorization conditions, a hierarchy
      of verb difficulty emerged. Subjects were more accurate in naming/categorizing
      one-place verbs than two-place verbs and more accurate in naming/categorizing two
      place verbs than three-place verbs. The pattern of selective impairment in
      lexical access/retrieval supports the hypothesis that one dimension of normal
      lexical organization is by form class. The results also suggest that no necessary
      relationship exists between production difficulties and comprehension of
      nouns/verbs in agrammatism. Further, the performance pattern noted supports the
      claim that verb-argument-structure properties, an important component of the verb
      lexicon, influence verb production at the single-word and at the sentence level.
      Subjects' performance on different tasks suggests that the locus of breakdown in
      the verb-retrieval processes for productionlike tasks may be in accessing
      information at the lemma level of representation as per Bock's model (1995) of
      sentence production.

PMID- 10924215
TI  - When does a deep dyslexic make a semantic error? The roles of age-of-acquisition,
      concreteness, and frequency.
AB  - Semantic reading errors are the central and defining feature of deep dyslexia.
      This study compared the words the deep dyslexic patient LW read correctly with
      those she omitted and those to which she produced semantic errors in terms of
      their concreteness, age-of-acquisition, frequency, and length. Semantic errors
      were made to less concrete, later-acquired, and shorter words than were read
      correctly; there was no reliable effect of word frequency. More importantly, the
      actual semantic errors produced were later-acquired than the stimulus words, but
      they were not more concrete or reliably more frequent. These results implicate
      age-of-acquisition in the process that produces semantic errors. It is proposed
      that concreteness determines the specificity of the semantic system to activate a
      set of candidate responses and that age-of-acquisition biases the ease with which
      certain words can be selected from this set to be produced as reading responses.

PMID- 10924216
TI  - Oral reading in dementia.
AB  - Reading has been thought to consist of three main processing components: the
      orthographic, phonological, and semantic lexicons. In traditional
      psycholinguistic models, these components have been treated independently such
      that the selective dysfunction of one does not necessarily imply the breakdown of
      another. Recently, it has been proposed that a word's semantic representation is
      essential to oral reading such that a disturbance within the semantic lexicon
      will disrupt processing within the orthographic and/or phonological lexicons.
      From this view, semantic deterioration should lead to fragmentation of the other
      systems contributing to reading, resulting in a specific pattern of errors during
      oral reading. This would include (1) a larger than normal advantage for reading
      words with regular spelling-to-sound correspondence over words with exception
      spelling, as well as the production of "regularization errors" when reading
      exception words; and (2) a smaller than normal difference between reading real
      words and pronounceable nonwords, or pseudowords (PW's). We found that patients
      with Semantic Dementia generally conformed to these hypothesized patterns of
      reading difficulty. Despite the presence of a semantic impairment, however,
      patients with Alzheimer's Disease, Frontotemporal Dementia, and Progressive Non
      Fluent Aphasia did not demonstrate these patterns of reading difficulty. Our
      findings suggest that not all semantic impairments invariably lead to the
      disruption of the orthographic and phonological lexicons.

PMID- 10924217
TI  - Rapid naming deficits in children and adolescents with reading disabilities and
      attention deficit hyperactivity disorder.
AB  - Seventy-one children in three groups (reading disabilities, ADHD without reading
      disabilities, and normal controls) were compared on their ability to rapidly name
      colors, letters, numbers, and objects (RAN Tasks) and alternating letters/numbers
      and letters/numbers/colors (RAS tasks). Children with reading disabilities were
      found to be slower on letter- and number-naming tasks and made more errors on all
      tasks than controls or children with ADHD. There was an age effect for the
      RAN/RAS tasks, with younger children with reading disabilities performing more
      poorly on all tasks, while the older children with reading disabilities showed
      poorer performance only on the letter- and number-naming tasks.

PMID- 10924218
TI  - The production of nominal compounds in aphasia.
AB  - This study reports the difficulties of aphasic patients in producing nominal
      compounds in German. In a picture naming task with semantically relatively
      transparent targets it was found that the word frequency of the components
      determined the accuracy of the patients' performance. A second picture naming
      task using relatively opaque targets, and a further naming task in which patients
      were confronted with aurally presented object paraphrases using very opaque
      targets, are reported. The error patterns of all three tasks give evidence for
      morpheme-based mis-productions (e.g., componential substitutions), however, in
      declining proportions with decreasing semantic transparency. Access to final (or
      basic) components was clearly superior to initial (or determinative) components
      suggesting position-specific access routines.

PMID- 10924219
TI  - The concreteness effect: evidence for dual coding and context availability.
AB  - The term concreteness effect refers to the observation that concrete nouns are
      processed faster and more accurately than abstract nouns in a variety of
      cognitive tasks. Two models have been proposed to explain the neuronal basis of
      the concreteness effect. The dual-coding theory attributes the advantage to the
      access of a right hemisphere image based system in addition to a verbal system by
      concrete words. The context availability theory argues that concrete words
      activate a broader contextual verbal support, which results in faster processing,
      but do not access a distinct image based system. We used event-related fMRI to
      detect the brain regions that subserve to the concreteness effect. We found
      greater activation in the lower right and left parietal lobes, in the left
      inferior frontal lobe and in the precuneus during encoding of concrete compared
      to abstract nouns. This makes a single exclusive theory unlikely and rather
      suggests a combination of both models. Superior encoding of concrete words in the
      present study may result from (1) greater verbal context resources reflected by
      the activation of left parietal and frontal associative areas, and (2) the
      additional activation of a non-verbal, perhaps spatial imagery-based system, in
      the right parietal lobe.

PMID- 10924220
TI  - Sulcal/gyral pattern morphology of the perisylvian language region in
      developmental dyslexia.
AB  - Two systems for classification of morphology of the perisylvian cortical area
      have been suggested, that of Steinmetz et al. (1990) and that of Witelson and
      Kigar (1992). This study examines whether the variations in placement of these
      convolutions in the language cortex are related to diagnosis of dyslexia in a
      clinic-referred sample of 55 children ages 8 to 12 years. Additionally, the
      systems are compared to determine their relationship to neurolinguistic
      performance. In this study, the Steinmetz et al. (1990) system captured
      morphological distinctions which were relevant to performance on neurolinguistic
      measures, while Witelson and Kigar's (1992) system did not. Under neither system
      was morphology associated with diagnosis of dyslexia.

PMID- 10924221
TI  - Dissociation of pure korean words and Chinese-derivative words in phonological
      dysgraphia.
AB  - Phonological dysgraphia is a writing impairment, characterized by marked
      disability to spell pronounceable pseudo-words as opposed to relatively mild
      reduction in ability to spell real words. Within the realm of Korean vocabulary,
      there are two categories of real words: pure Korean words and Chinese-derivative
      words. We present a patient with a history of CVA, resulting in phonological
      dysgraphia and, further, a dissociated performance in the aforementioned two
      categories of real words. It is suggested that the lexicon for pure Korean words
      is segregated from that for Chinese-derivative words.

PMID- 10924222
TI  - Ultradian rhythms in cells: questions regarding their existence and significance.

PMID- 10924223
TI  - Ultradian rhythms: introductory remarks.

PMID- 10924224
TI  - Problems associated with the study of cellular oscillations.
AB  - Data from the article by Brodsky et al. (2000) have been examined in order to
      confirm that the fluctuations they report are not random but have a rhythmic
      basis, thereby verifying their conclusions regarding the existence of periodicity
      in protein synthesis. Reasons are outlined why oscillations should be expected in
      all cellular biochemical studies. Associated practical problems are briefly
      discussed together with comments on the validity and value of less rigorous
      methods of analysis. The subject of aliasing is raised as justification for
      doubting the validity of much published data, especially where periodicity has
      not been suspected. The existence of oscillations indicates the need for a
      thorough re-evaluation of our understanding of cell biochemistry.

PMID- 10924225
TI  - Multiple respiratory bursts as a response to veratrate stress in Rhodococcus
      erythropolis cells.
AB  - Although Rhodococcus spp. strains are able to degrade methoxyphenols by enzymatic
      means, the contact with veratric acid (3, 4-dimethoxybenzoic acid, hereafter
      called veratrate) is very stressful for the cells of Rhodococcus erythropolis DSM
      1069 (Rh). Within 5 min of contact veratrate in phosphate buffer, the emergence
      of many vacuoles was observed in the cell body and respiratory bursts, with
      violent endogenous oxygen uptake, took place several times during the 24 h
      incubation. During these peaks (where the cells were in their MAX states),
      increased activity of NADH oxidase was noted, accompanied by maximal accumulation
      of vanillic and isovanillic acids (3-methoxy-4-hydroxybenzoic acid and 4-hydroxy
      3-methoxybenzoic acid respectively, hereafter called vanillates) in the
      incubation medium, which appeared to be products of veratrate demethylation. At
      the troughs (cell in their MIN state), the vacuoles disappeared from the cell
      body, oxygen uptake was normal, and the pool of vanillates decreased while the
      veratrate level in the medium increased. The cells from MAX and MIN states
      reacted in opposite ways in the presence of either formaldehyde and GSH, or
      paraquate and cAMP. The NADH oxidase activity, measured as oxygen uptake against
      NADH in the membrane pellets of MAX and MIN stage cells, differed in their
      response to the exogenous presence of FAD, ATP, cAMP, catalase, GSH, H(2)O(2)and
      methoxyphenolic substrates. The periodic character of these events is described
      here. Co-operation between two multiprotein membrane complexes (NAD(P)H oxidase
      and 3-O/4-O-demethylases) in Rhodococcus erythropolis cells and their competition
      for two common substrates-NAD(P)H and O(2)-is proposed as an explanation for
      rhythmical nature of these reactions.

PMID- 10924226
TI  - Rhythmic patterns in the expression of the ras oncogene in proliferating and
      differentiating erythroleukaemia cells.
AB  - Temporal variations in the expression of the ras oncogene, and its protein
      product, were investigated during hexamethylene bisacetamide (HMBA)-induced
      differentiation of murine erythroleukaemic (MEL) cells. We highlight the fact
      that when comparisons were made between untreated, proliferating cells and HMBA
      treated, differentiating cells using only one time-point, differences, both for
      the expression of the gene and the protein, were in most cases insignificant;
      standard deviations were high and the interpretation could be made that HMBA had
      little effect. Such interpretation fails to take account of the dynamic nature of
      the system, with single time-point studies giving incomplete information, which
      can be misleading. Multiple time analyses showed clearly that rhythmic patterns
      of expression were modulated by the differentiating agent. Time-dependent changes
      in the expression of mRNA specific to H- ras and N- ras, as well as in the
      expression of the Ras protein, when measured over periods of minutes or hours,
      were apparent. HMBA affected frequency and phasing of the rhythms. Regulation of
      the dynamics in this way may be crucial to the control of cell function and
      transformation.

PMID- 10924227
TI  - Modulation of the rhythmic patterns of expression of phosphoprotein phosphatases
      in human leukaemia cells.
AB  - Temporal variations in the expression of phosphoprotein phosphatase 1 (PP1),
      phosphoprotein phosphatase 2A (PP2A) and protein tyrosine phosphatase 1B (PTP1B)
      were monitored in the human acute, promyelocytic leukaemia cell line, HL60.
      Granulocytic differentiation was induced using all-trans retinoic acid (ATRA) and
      monocytic differentiation by phorbol-12-myristate-13-acetate (PMA). Expression of
      the enzyme proteins in cell extracts was determined by SDS-PAGE and Western
      immunoblotting using specific antibodies. For PP1, a single immunospecific band
      of molecular mass 38 kDa was detected corresponding to the catalytic subunit;
      induction of differentiation with either ATRA or PMA showed differences in the
      patterns of expression and, in the case of the latter, the mean value. Two
      immunospecific bands, of mass 34 and 37 kDa, possibly corresponding to
      dephosphorylated and phosphorylated forms, respectively, were detected for PP2A,
      as well as a minor band of mass 46 kDa; dynamic variations in the expression of
      all 3 forms were observed and there were differences between the control and
      treated cells. The catalytic domain of PTP1B was detected as a 46 kDa band. A 42
      kDa form of the protein was also seen, which may represent a change in
      phosphorylation state, or be the result of proteolytic cleavage; usually the 46
      kDa band was the major form, but on occasion there was a change to predominance
      of the 42 kDa band.

PMID- 10924228
TI  - Protein kinase c in erythroleukaemia cells: temporal variations in the expression
      of the alpha, epsilon and zeta isoforms.
AB  - Determinations of mRNA and enzyme protein analyses for the protein kinase C (PKC)
      isoforms, alpha, epsilon and zeta, representing the classical, novel and atypical
      groups, respectively, in murine erythroleukaemic (MEL) cells revealed the
      occurrence of cyclic behaviour in expression. Such rhythmicity was not apparent
      when multiple analyses using only a single time-point were considered; the
      importance of incorporating a time component into experimental design was
      demonstrated. On induction of differentiation over a period of five days with
      hexamethylene bisacetamide, changes in the patterns of expression of mRNA and
      protein were apparent, as compared with those of untreated, proliferating cells.
      Modulation of the dynamics of the various PKC isoforms may represent a regulatory
      mechanism for the control of a diversity of cellular functions.

PMID- 10924229
TI  - Temporal variations in protein tyrosine phosphatase activity during cell
      proliferation and differentiation.
AB  - Cellular oscillations in total extractable protein content and protein tyrosine
      phosphatase activity were analysed in proliferating and differentiating human
      acute promyelocytic leukaemic (HL-60) cell extracts. Differentiation was induced
      along the granulocytic pathway using all-trans retinoic acid (ATRA). High
      frequency rhythms with distinct, well defined waveforms of varying amplitude were
      observed for both the total protein content and for the enzyme activity of
      protein tyrosine phosphatase (PTP). Linear correlation analysis showed that there
      was no obvious relationship between the protein content and the corresponding PTP
      activity, suggesting that the periodic variations between these two components
      are relatively independent of each other. ATRA significantly altered the
      characteristics of the rhythms with respect to the period and amplitude and had a
      dampening effect on the oscillatory pattern of PTP activity. Modulation of such
      characteristics may be of significance with respect to the regulation of the
      differentiation processes and the possible reversal of transformation.

PMID- 10924230
TI  - The living cell: a complex autodynamic multi-oscillator system?
AB  - Life cannot be simply defined in biochemical terms but it is associated with
      autodynamic behaviour. This fact implies that all aspects of cell biology should
      be viewed in terms of the resultant temporal features. Theoretical arguments
      indicate that the dynamic state can be explained only by the existence of
      periodicity. In accordance with this view, experimental evidence indicates the
      existence of multiple oscillators and at least some are highly complex, implying
      that failure to understand aspects of cell biology can stem from inadequate
      concepts.

PMID- 10924231
TI  - Chaotic dynamics and fractal space in biochemistry: simplicity underlies
      complexity.
AB  - In this work we attempt to analyze the coupling between the dynamics of
      biochemical reactions (especially chaotic dynamics), and the geometry of
      cytoarchitecture (especially fractal ultrastructure), because of its importance
      and consequences for the ultradian dynamic behaviour of cells. Fractal geometry
      in intracellular macromolecular assemblies suggests that chaotic dynamics occur
      during their organization. Non-linear interactions in and between spatial and
      temporal domains and over wide ranges of scales underlie the emergent properties
      of complex biological systems.

PMID- 10924233
TI  - Metacognition and consciousness: A convergence of psychology and philosophy

PMID- 10924232
TI  - Transient chaos in intracellular dynamics?
AB  - Periodogram analyses of the temporal variations of several cellular oscillations
      occasionally reveal the existence of short duration bands containing a wide range
      of frequencies. The possibility is considered that these are due to the transient
      compliance with chaotic conditions.

PMID- 10924234
TI  - The feeling of knowing: some metatheoretical implications for consciousness and
      control.
AB  - The study of the feeling of knowing may have implications for some of the
      metatheoretical issues concerning consciousness and control. Assuming a
      distinction between information-based and experience-based metacognitive
      judgments, it is argued that the sheer phenomenological experience of knowing
      ("noetic feeling") occupies a unique role in mediating between implicit-automatic
      processes, on the one hand, and explicit-controlled processes, on the other.
      Rather than reflecting direct access to memory traces, noetic feelings are based
      on inferential heuristics that operate implicitly and unintentionally. Once such
      heuristics give rise to a conscious feeling that feeling can then affect
      controlled action. Examination of the cues that affect noetic feelings suggest
      that not only do these feelings inform controlled action, but they are also
      informed by feedback from the outcome of that action.

PMID- 10924235
TI  - Probing for relevance: what metacognition tells us about the power of
      consciousness.
AB  - Metacognitive attitudes can affect behavior but do they do so, as Koriat claims,
      because they enhance voluntary control? This Commentary makes a case for saying
      that metacognitive consciousness may enhance not control but subjective
      predictability and may be best studied by examining not just healthy, well
      integrated cognizers, but victims of multilevel mental disorders.

PMID- 10924236
TI  - Feelings and judgments of knowing: is there a special noetic state?
AB  - A. Koriat distinguishes between feeling-based and inferentially based feeling-of
      knowing judgments. The former are attributable to partial information that is
      activated in implicit memory but not fully articulated. They are not, however,
      attributable to direct access to the target-an hypothesis that Koriat
      specifically repudiates. While there is considerable merit in the distinction
      that Koriat draws, and his emphasis on the possibility that people base at least
      some of their metacognitive judgments on implicit information seems well founded,
      it is argued that his rejection of the direct access view is premature. There may
      be a state-a true noetic state-in which people actually know the answer before
      they are able to express it. A case is made for further consideration of the
      scientific merits of the direct-access view of the noetic feelings people
      experience in imminent tip-of-the-tongue (TOT) states.

PMID- 10924237
TI  - The unconscious feeling of knowing: a commentary on Koriat's paper.
AB  - In Koriat's paper "The Feeling of Knowing: Some Metatheoretical Implications for
      Consciousness and Control," he asserts that the feeling of knowing straddles the
      implicit and explicit, and that these conscious feelings enter into a conscious
      control process that is necessary for controlled behavior. This assertion allows
      him to make many speculations on the nature of consciousness itself. We agree
      that feelings of knowing are produced through a monitoring of one's knowledge,
      and that this monitoring can affect the control of behavior such as whether or
      not to search memory for an answer. Further, we believe that monitoring of
      performance with a strategy can also affect cognition control and strategy
      selection; however, we also believe that frequently this monitoring and control
      occurs without conscious awareness. Feeling of knowing has received an inordinate
      amount of attention because it lies behind the highly recognizable tip-of-the
      tongue phenomenon that represents one of the rare cases of conscious monitoring.
      There are other feelings of knowing which are much more common and are not
      accompanied by conscious awareness. These are evident in the early selection of a
      strategy for answering a problem. In our view, the research on feeling of knowing
      will not resolve the question of whether consciousness is merely epiphenomenal.

PMID- 10924238
TI  - Conscious and unconscious metacognition: A rejoinder
AB  - In this rejoinder we clarify several issues raised by the commentators with the
      hope of resolving some disagreements. In particular, we address the distinction
      between information-based and experience-based metacognitive judgments and the
      idea that memory monitoring may be mediated by direct access to internal
      representations. We then examine the possibility of unconscious metacognitive
      processes and expand on the critical role that conscious metacognitive feelings
      play in mediating between unconscious activations and explicit-controlled action.
      Finally, several open questions are articulated for further scrutiny. Copyright
      2000 Academic Press.

PMID- 10924239
TI  - Consciousness, content, and metacognitive judgments.
AB  - Because metacognition consists in our having mental access to our cognitive
      states and mental states are conscious only when we are conscious of them in some
      suitable way, metacognition and consciousness shed important theoretical light on
      one another. Thus, our having metacognitive access to information carried by
      states that are not conscious helps confirm the hypothesis that a mental state's
      being conscious consists in having a noninferential higher-order thought about
      that state. This higher-order-thought hypothesis readily explains the appearance
      to consciousness of confabulatory mental states-states that do not actually
      occur. This fits well with, and helps refine, the "No-Magic Hypothesis" advanced
      by Nelson and Narens (1990).

PMID- 10924240
TI  - Comments on David Rosenthal's "Consciousness, content, and metacognitive
      judgments".

PMID- 10924241
TI  - Consciousness, self-consciousness, and metacognition.

PMID- 10924243
TI  - Metacognition and higher-order thoughts

PMID- 10924242
TI  - Role, not content: comments on David Rosenthal's "Consciousness, content, and
      metacognitive judgments".

PMID- 10924244
TI  - A neurofunctional theory of visual consciousness.
AB  - This paper develops an empirically motivated theory of visual consciousness. It
      begins by outlining neuropsychological support for Jackendoff's (1987) hypothesis
      that visual consciousness involves mental representations at an intermediate
      level of processing. It then supplements that hypothesis with the further
      requirement that attention, which can come under the direction of high level
      representations, is also necessary for consciousness. The resulting theory is
      shown to have a number of philosophical consequences. If correct, higher-order
      thought accounts, the multiple drafts account, and the widely held belief that
      sensation precedes perception will all be found wanting. The theory will also be
      used to illustrate and defend a methodology that fills the gulf between
      functionalists who ignore the brain and neural reductionists who repudiate
      functionalism.

PMID- 10924245
TI  - Comments on "A neurofunctional theory of visual consciousness".

PMID- 10924246
TI  - On a neurofunctional theory of visual consciousness: commentary on J. Prinz.

PMID- 10924247
TI  - A reply to lormand

PMID- 10924248
TI  - A reply to marcel

PMID- 10924249
TI  - Executive attention and metacognitive regulation.
AB  - Metacognition refers to any knowledge or cognitive process that monitors or
      controls cognition. We highlight similarities between metacognitive and executive
      control functions, and ask how these processes might be implemented in the human
      brain. A review of brain imaging studies reveals a circuitry of attentional
      networks involved in these control processes, with its source located in
      midfrontal areas. These areas are active during conflict resolution, error
      correction, and emotional regulation. A developmental approach to the
      organization of the anatomy involved in executive control provides an added
      perspective on how these mechanisms are influenced by maturation and learning,
      and how they relate to metacognitive activity.

PMID- 10924250
TI  - Metacognition and awareness.
AB  - It is tempting to assume that metacognitive processes necessarily evoke
      awareness. We review a number of experiments in which cognitive schema have been
      shown to develop without awareness. Implicit learning of a novel schema may not
      involve metacognitive regulation per se. Substitution of one automatic process by
      another as a result of the inadequacy of the former as circumstances change does,
      however, clearly involve metacognitive and executive processes of error
      correction and schema selection. We describe a recently published study in which
      we serendipitously discovered that a blindsight subject could change the schema
      with which he processed cue information in orienting spatial attention task
      without reporting any awareness of this change, or of the cues and targets which
      respectively directed and were the object his attention.

PMID- 10924251
TI  - Toward a cognitive neuroscience of metacognition.
AB  - The relationship between metacognition and executive control is explored.
      According to an analysis by Fernandez-Duque, Baird, and Posner (this issue),
      metacognitive regulation involves attention, conflict resolution, error
      correction, inhibitory control, and emotional regulation. These aspects of
      metacognition are presumed to be mediated by a neural circuit involving
      midfrontal brain regions. An evaluation of the proposal by Fernandez-Duque et al.
      is made, and it is suggested that there is considerable convergence of issues
      associated with metacognition, executive control, working memory, and frontal
      lobe function. By integrating these domains and issues, significant progress
      could be made toward a cognitive neuroscience of metacognition.

PMID- 10924252
TI  - Awareness and metacognition
AB  - Kentridge and Heywood (this issue) extend the concept of metacognition to include
      unconscious processes. We acknowledge the possible contribution of unconscious
      processes, but favor a central role of awareness in metacognition. We welcome
      Shimamura's (this issue) extension of the concept of metacognitive regulation to
      include aspects of working memory, and its relation to executive attention.
      Copyright 2000 Academic Press.

PMID- 10924254
TI  - The combination of bcl-2 expression and NGF-deprivation facilitates the selective
      destruction of BAD protein in living sympathetic neurons.
AB  - Bcl-2 overexpression prevents neuronal death after injury or neurotrophic factor
      deprivation but the biochemical consequences of survival maintenance by Bcl-2
      have hardly been explored. We show that unlike NGF, adenovirally delivered hBcl-2
      supports the survival of over 80% of the neurons without activating ERK and Akt
      phosphorylation, or suppressing JNK phosphorylation, or enhancing cell growth.
      However, the proapoptotic protein BAD, whose phosphorylation is induced by NGF,
      is degraded in NGF-deprived neurons expressing hBcl-2, while the level of Bcl-xL
      remains unaffected. Interestingly, degradation of BAD protein is prevented by the
      pan-caspase inhibitor Boc.Asp(OMe)fmk. We propose that NGF-deprivation promotes
      dephosphorylation of BAD while hBcl-2 facilitates its release into the cytoplasm
      where it is degraded by noncaspase, Boc.Asp(O-Me)fmk-inhibitable proteases. The
      potential importance of BAD degradation is suggested by our finding that
      overexpressed BAD kills NGF-maintained sympathetic neurons by apoptosis, while
      hBcl-2 prevents BAD-induced death.

PMID- 10924253
TI  - Transgenic mice overexpressing truncated trkB neurotrophin receptors in neurons
      show increased susceptibility to cortical injury after focal cerebral ischemia.
AB  - It has been suggested that the increased production of endogenous BDNF after
      brain insults supports the survival of injured neurons and limits the spread of
      the damage. In order to test this hypothesis experimentally, we have produced
      transgenic mouse lines that overexpress the dominant-negative truncated splice
      variant of BDNF receptor trkB (trkB.T1) in postnatal cortical and hippocampal
      neurons. When these mice were exposed to transient focal cerebral ischemia by
      occluding the middle cerebral artery for 45 min and the damage was assessed 24 h
      later, transgenic mice had a significantly larger damage than wild-type
      littermates in the cerebral cortex (204 +/- 32% of wild-type, P = 0.02), but not
      in striatum, where the transgene is not expressed. Our results support the notion
      that endogenously expressed BDNF is neuroprotective and that BDNF signaling may
      have an important role in preventing brain damage after transient ischemia.

PMID- 10924255
TI  - Endogenous presenilin-1 targets to endocytic rather than biosynthetic
      compartments.
AB  - Presenilin-1 (PS1), which is linked to familial Alzheimer's disease, participates
      in the proteolytic processing of Notch and amyloid-beta precursor protein (APP)
      by an unknown mechanism. Reports of PS1 localization to the endoplasmic reticulum
      (ER) and Golgi apparatus have focused attention on the early biosynthetic pathway
      as the site of PS1 function. However, it is unclear how Notch cleavage and APP
      processing events which occur at or near the cell surface are influenced by PS1.
      In contrast to some earlier studies, examination of endogenously expressed PS1 in
      PC12 cells by subcellular fractionation and immunofluorescence microscopy
      revealed a distribution distinct from that of ER and Golgi markers. Rather, PS1
      colocalized with transferrin receptor, a marker for early endosomes. In addition,
      electron microscopic examination of intact vesicles immunoisolated with PS1
      antibodies allowed visualization of endocytic tracer in endosomes. These findings
      identify an early endosomal pool of PS1 and suggest alternative mechanisms for
      PS1 interactions with APP and Notch.

PMID- 10924256
TI  - Identification and characterization of differentially expressed genes in
      denervated muscle.
AB  - Denervation results in a series of changes in skeletal muscle. To elucidate the
      molecular basis underlying these changes, it is important to identify the profile
      of altered gene expression in skeletal muscle following nerve injury. In the
      present study, we have examined the differentially expressed genes in denervated
      gastrocnemius muscle using RNA fingerprinting by arbitrarily primed PCR. Eight
      differentially expressed mRNA transcripts have been identified. A bilateral
      regulatory profile can be observed for the up-regulated genes in both denervated
      and contralateral control muscle following unilateral sciatic nerve injury. The
      temporal expression profiles of the denervation-regulated genes in muscle during
      development, together with their dependency on nerve activity, suggest potential
      functional roles following nerve injury in vivo. In particular, the
      identification of two apoptosis-related genes in denervated muscle provides
      molecular evidence that the apoptotic process is likely to be involved in the
      intricate changes that lead to muscle atrophy. Our findings not only allow the
      identification of novel genes, but also suggest possible functions for some known
      genes in muscle following nerve injury. Taken together, these findings provide
      important insights into our understanding of the molecular events in denervated
      muscle and suggest that the differentially expressed genes may play potential
      roles during muscle denervation and regeneration.

PMID- 10924257
TI  - Abnormal polarization and axon outgrowth in retinal ganglion cells lacking the
      POU-domain transcription factor Brn-3b.
AB  - The POU domain transcription factor Brn-3b (also called Brn-3.2) is essential for
      the normal development of retinal ganglion cells (RGCs) in the mouse. Without Brn
      3b, RGCs commit to their fate and migrate to the ganglion cell layer, but most
      cells die during fetal development. An earlier report (L. Gan et al., 1999, Dev.
      Biol. 210, 469-480) suggested that cell death was caused by abnormal axon
      formation. Here, we use retinal explants from wild-type and mutant embryos to
      show that brn-3b-deficient RGCs are not properly polarized and tend to form
      dendrites rather than axons. Compared with wild-type explants, neurites of RGCs
      from brn-3b-deficient retinal explants grew slower, were shorter, and did not
      fasciculate properly. Mutant neurites had more microtubules than wild-type
      controls, and the arrangement of microtubules and neurofilaments was
      characteristic of dendrites rather than axons. Neurites from individual mutant
      RGCs displayed abnormal polarity and had dendrite-like branches extending outward
      from their main axis. Most mutant RGCs exhibited abnormal migratory behavior, and
      their neurites labeled intensely with the dendrite marker MAP-2. A small number
      of mutant RGCs were not migratory, and their neurites were longer and labeled
      positively for the axon marker tau-1, suggesting that some RGCs were not as
      severely affected by the absence of Brn-3b as others. Although tau-1 was not
      observed in most mutant neurites, it did accumulate in mutant cell bodies,
      implying that the absence of Brn-3b caused a defect in axon transport. Thus, Brn
      3b appears to control the activity of genes that function in establishing RGC
      polarity, and without Brn-3b, RGCs cannot extend normal axons.

PMID- 10924258
TI  - MMP-2 and MMP-9 increase the neurite-promoting potential of schwann cell basal
      laminae and are upregulated in degenerated nerve.
AB  - Compared to degenerated nerves, the ability of normal adult peripheral nerve to
      support axonal regeneration is poor and may be attributed to the inhibition of
      endoneurial laminin by chondroitin sulfate proteoglycan (CSPG). In cryoculture
      assays, neuritic growth of neonatal and adult peripheral neurons was increased on
      sections of normal nerve by pretreatment with CSPG-degrading enzymes, including
      the matrix metalloproteinases MMP-2 and MMP-9. Axonal regeneration is known to
      occur within the Schwann cell basal laminae of degenerated nerve. Similarly,
      deconvolution microscopy revealed that neuritic growth on nerve tissue sections
      occurred principally on the lumenal surface of enzymatically modified basal
      laminae. Compared to normal nerve, there was a marked increase in the neurite
      promoting activity of the degenerated nerve, and this activity was not increased
      significantly by subsequent MMP treatment. Additionally, the expression and
      activation of MMP-2 and MMP-9 were elevated in degenerated nerve, suggesting that
      degradation of inhibitory CSPG by the MMPs contributes to the growth-promoting
      properties of degenerated nerve.

PMID- 10924259
TI  - Expression of huntingtin-associated protein-1 in neuronal cells implicates a role
      in neuritic growth.
AB  - Huntingtin-associated protein-1 (HAP1) binds more tightly to mutant huntingtin,
      but its function and distribution in neurites are not clear. Using PC12 cells and
      cultured hippocampal neurons, we found that two HAP1 isoforms, HAP1-A and HAP1-B,
      have different subcellular localizations. While most HAP1-B is diffusely
      distributed within the cytoplasm, HAP1-A is enriched in the growth cones and
      neuritic puncta of developing neurons. In mature neurons and adult brain neurons,
      however, HAP1-A is concentrated in axon terminals and associated with synaptic
      vesicles. Transfection of HAP1-A in PC12 cells significantly promotes neurite
      extension, with HAP1-A distributed in the distal regions of the growing neurites.
      Cotransfection of mutant huntingtin with HAP1-A in PC12 cells results in the
      accumulation of HAP1-A on huntingtin aggregates and the inhibition of neurite
      promotion by HAP1-A. This study suggests that HAP1-A has a function in neuritic
      development and synaptic function and that mutant huntingtin may alter this
      function.

PMID- 10924260
TI  - Effects of high-molecular-weight cryoprotectants on platelets and the coagulation
      system.
AB  - The objective of this study is to examine the effects of the most widely used
      high-molecular-weight cryoprotectants on the coagulation system. Dextran,
      hydryoxyethyl starch (HES), polyvinyl pyrrolidone (PVP), polyethylene glycol
      (PEG), and albumin were added at different concentrations in the range between
      0.01-1% (w/v) to solvent/detergent-treated plasma. Using a STA/STA Compact
      coagulation analyzer the following clotting tests were performed: prothrombin
      time (PT), activated partial thromboplastin time (APTT), thrombin time (TT),
      Factor V, and Factor VIII percentage of activity. PVP and PEG caused a
      significant increase in APTT, a decrease in Factor VIII percentage of activity,
      and a slight decrease in TT, while PT and Factor V percentage of activity
      remained unchanged. Dextran, HES, and albumin did not effect the clotting tests.
      The effect of high-molecular-weight cryoprotectants on platelets was assessed by
      platelet-induced clot retraction (PICR) and aggregation with thrombin and
      agglutination with ristocetin. Platelet aggregation and agglutination were
      unaffected by all cryoprotectants tested; however, PICR was significantly reduced
      in the presence of PVP or PEG. Possible mechanisms by which PVP and PEG interfere
      with the coagulation system are discussed. We also raise issues concerning the
      development of one-step blood cryopreservation techniques which do not require
      cryoprotectant removal prior to transfusion.

PMID- 10924261
TI  - Photoperiodic and thermal regulation of development and cold hardiness in larvae
      of the clover leaf weevil, Hypera punctata.
AB  - Effects of photoperiod and temperature on the development and cold hardiness were
      investigated in larvae of Hypera punctata. At a relatively low temperature (15
      degrees C), the larvae fed less and developed more slowly under a 12L:12D (SD)
      photoperiod than under a 16L:8D photoperiod (LD). SD larvae had lower gut weight
      against the whole body weight and lower supercooling point (SCP) than the LD
      counterparts for the same instar and same body weight. This was because the
      larval SCP is markedly affected by the quantity of the gut content. Laboratory
      experiments indicated that the low temperature mortality of this larvae occurred
      mainly due to freezing irrespective of the photoperiod and temperature,
      suggesting that the lower lethal temperature (LLT) depends on the supercooling
      ability of larvae. The SD larvae tended to have a lower SCP and hence a lower LLT
      than the LD counterparts at 15 or 10 degrees C, unlike at 20 degrees C. Thus, the
      slower larval development under SD conditions at relatively low temperatures may
      prevent larvae from reaching the later instar, which have a higher SCP and thus
      less cold tolerance, during the coldest season. The suppressed feeding activity
      under SD conditions would lower the SCP, thereby reducing the possibility of
      lethal tissue freezing. Such a photoperiodic and thermal regulation of the larval
      development and the supercooling ability appear to represent adaptive mechanisms
      for winter survival in this beetle.

PMID- 10924262
TI  - Comparison of iceball diameter and temperature distribution achieved with 3-mm
      accuprobe cryoprobes in porcine and human liver tissue and human colorectal liver
      metastases in vitro.
AB  - We aimed to assess the thermal profile and size of iceballs produced by Accuprobe
      cryoprobes in fresh porcine and human liver and human colorectal cancer liver
      metastases in vitro to allow better planning of cryosurgical treatment of liver
      metastases. Iceballs were produced by a 20-min single freeze cycle using 8-mm
      cryoprobes in pig liver in a waterbath at 37 degrees C (n = 8) and 3-mm
      cryoprobes in pig liver (n = 8), human liver (n = 3), and human colorectal cancer
      liver metastases (n = 8). The iceball diameters and the temperatures at different
      distances from the cryoprobe were measured. Mean iceball diameters produced by 8
      mm cryoprobes in pig liver were 56.3 mm and varied from 38.7 to 39.6 mm for 3-mm
      cryoprobes in the different tissues used. There was no significant difference in
      iceball size in the different tissues. The diameter of the zone of -40 degrees C
      or less was approximately 44 mm using 8-mm cryoprobes in porcine liver and
      between 27 and 31 mm using 3-mm cryoprobes in the different tissues examined. The
      results may allow better preoperative planning of the cryosurgical treatment of
      liver metastases with Accuprobe cryoprobes.

PMID- 10924263
TI  - Extended alternating-temperature cold acclimation and culture duration improve
      pear shoot cryopreservation.
AB  - Meristems of many pear genotypes can be successfully cryopreserved following 1
      week of cold acclimation, but an equal number do not survive the process or have
      very little regrowth. This study compared commonly used cold acclimation
      protocols to determine whether the cold acclimation technique used affected the
      cold hardiness of shoots or the regrowth of cryopreserved meristems. In vitro
      grown pear (Pyrus L.) shoots were cold acclimated for up to 16 weeks, then either
      the shoot tips were tested for cold hardiness or the meristems were cryopreserved
      by controlled freezing. Cold acclimation consisted of alternating temperatures
      (22 degrees C with light/-1 degrees C darkness with various photo- and
      thermoperiods) or a constant temperature (4 degrees C with an 8-h photoperiod or
      darkness). Compared with nonacclimated controls, both alternating- and constant
      temperature acclimation significantly improved postcryopreservation regrowth of
      P. cordata Desv. and P. pashia Buch. -Ham. ex D. Don meristems. Alternating
      temperature acclimation combined with either an 8-h photoperiod or darkness was
      significantly better than constant-temperature acclimation. Alternating
      temperature shoot acclimation for 2 to 5 weeks significantly increased
      postcryopreservation meristem regrowth, and recovery remained high for up to 15
      weeks acclimation. Postcryopreservation meristem regrowth increased with 1 to 5
      weeks of constant-temperature acclimation and then declined with longer
      acclimation. Shoot cold hardiness varied with the acclimation procedure. The
      LT(50) of shoots acclimated for 10 weeks with alternating temperatures was -25
      degrees C; that with constant temperature was -14.7 degrees C; and that of the
      nonacclimated control was -10 degrees C. Less frequent transfer of cultures also
      improved acclimation of shoots. Shoots grown without transfer to fresh medium for
      6-12 weeks had higher postcryopreservation recovery with shorter periods of
      acclimation than shoots with a 3-week transfer cycle.

PMID- 10924264
TI  - Purification and characterization of protein kinase A from liver of the freeze
      tolerant wood frog: role in glycogenolysis during freezing.
AB  - Freeze tolerance by various amphibians includes cryoprotectant production in the
      form of glucose. Activation of the catalytic subunit of liver cAMP-dependent
      protein kinase (PKAc) facilitates activation of glycogenolysis, a critical
      biochemical process necessary for production of glucose. Here, we purified PKAc
      from Rana sylvatica liver to determine the extent to which cold temperature,
      which stimulates cryoprotectant production, affected PKAc activity and function.
      PKAc was purified to greater than 95% homogeneity, with a final specific activity
      of 71 nmol phosphate transferred/min/mg protein. The molecular weight of frog
      liver PKAc was 47.6 +/- 1.1 kDa and K(m) values for the phosphate acceptor
      kemptide and Mg-ATP were 9.0 +/- 0.1 and 51.8 +/- 1.0 microM at 22 degrees C,
      respectively. K(m) values for both substrates dropped significantly at 5 degrees
      C. The enzyme was sensitive to specific inhibitors of mammalian PKAc (PKA(i),
      H89) but was only moderately inhibited by high salt concentrations. Furthermore,
      salt inhibition was reduced at low temperature. The effect of temperature on
      enzyme activity indicated a conformational change in PKAc at 10 +/- 2 degrees C,
      with calculated activation energies of 51 +/- 4 kJ/mol at temperatures above 10
      degrees C and 110 +/- 9 kJ/mol below 10 degrees C. PKAc in wood frog liver plays
      a crucial role in mediating the freeze-induced glycogenolysis that is responsible
      for the production of 200-300 mM levels of glucose as a cryoprotectant.
      Differential effects of low temperature on enzyme function, increased substrate
      affinity and reduced ion inhibition, appear to be central to this role.

PMID- 10924265
TI  - Gene up-regulation in heart during mammalian hibernation.
AB  - A cDNA library prepared from heart of hibernating golden-mantled ground
      squirrels, Spermophilus lateralis, was differentially screened to clone genes
      that were up-regulated during hibernation. Two differentially expressed clones
      were found after three rounds of screening and were confirmed as up-regulated by
      Northern blotting. Clone Ang6 encoded a polypeptide with 116 amino acids that was
      identified as the ventricular isoform of myosin light chain 1 (MLC1(v)). Clone
      Ang19 coded for 274 amino acid residues of the mitochondrially encoded protein
      subunit 2 of NADH-ubiquinone oxidoreductase (ND2). Both proteins showed high
      amino acid sequence identity with their human counterparts, 97.5% for MLC1(v) and
      66% for ND2. Northern blot hybridization revealed differential expression of
      these genes in multiple organs during hibernation. Transcript levels of both were
      approximately twofold higher in heart and three- to fourfold higher in skeletal
      muscle of hibernating, versus euthermic, animals. ND2 was also up-regulated in
      hibernator liver. Hibernation-induced up-regulation of MLC1(v) suggests that a
      restructuring of myosin subunit composition could contribute to changes in muscle
      contractility needed for hypothermic function, whereas changes in ND subunit
      composition may affect the function of the electron transport chain during
      hibernation.

PMID- 10924267
TI  - Green fluorescent protein: A novel viability assay for cryobiological
      applications.
AB  - Assessment of tissue viability following the application of a freezing protocol
      is challenging due to the paucity of viability assays that can be used
      dynamically, in situ. Cells transfected with a green fluorescent protein (GFP)
      vector actively produce GFP, which is retained intracellularly. Because of its
      constitutive and heritable expression, GFP fluorescence of transfected cells may
      have significant utility as a viability assay for cells within tissues. As a
      first step toward application to tissues, this work seeks to establish the
      validity of this GFP-based assay in cell suspensions by comparing the results to
      other accepted measures of viability. To the authors' knowledge, this is the
      first use of GFP in cryobiology applications. Intracellular GFP fluorescence was
      evaluated following slow freezing. Nontransfected and GFP-transfected rat 3230
      adenocarcinoma (R3230AC) cells were frozen at 1 degrees C/min to minimum
      temperatures between -5 and -30 degrees C and then immediately thawed in a 37
      degrees C water bath. Samples were assayed using the common viability indicators
      trypan blue and ethidium bromide (EtBr). A regression analysis of recovery
      measured with the GFP assay as a function of recovery measured with a trypan blue
      assay gave a correlation coefficient of 0.97. A similar correlation coefficient,
      0.95, was determined for recovery assessed by the GFP assay as a function of
      recovery measured by an EtBr assay. Nontransfected and GFP-transfected cells
      responded similarly to slow freezing, indicating that GFP transfection did not
      significantly alter the response of cells to typical freezing conditions. The
      excellent correlation of GFP assay results with those of two common viability
      assays suggests that the GFP-based assay is valid for cells and that further
      development of a tissue viability assay based on transfection is appropriate.

PMID- 10924266
TI  - Reversible cross-linking and CO treatment as an approach in red cell
      stabilization.
AB  - We explored the use of the reversible cross-linking reagent dimethyl 3,3
      dithiobispropionimidate (DTBP) in combination with CO treatment as an approach to
      stabilizing erythrocyte structure and function. Erythrocytes were cross-linked
      with different concentrations of DTBP for different times. DTBP increased
      erythrocyte osmotic stability, blocked lysolecithin-induced echinocytosis, and
      decreased erythrocyte deformability in a concentration- and time-dependent
      manner. Reversal of the cross-linking with the reducing agent dithioerythritol
      (DTE) restored osmotic fragility and response to lysolecithin as well as
      deformability. Complete reversal, however, is a function of the DTBP
      concentration and the time of cross-linking. The effects of cross-linking with 5
      mM DTBP for 1 h were completely reversible after treatment with 10 mM DTE for 20
      min. Longer incubation times or higher concentrations of DTBP resulted in partial
      reversal by DTE of the effects produced by DTBP. Cross-linking and reversal only
      slightly reduced the ATP content. The hemoglobin contained in the cross-linked
      and reversed cells could still undergo reversible oxygenation and deoxygenation.
      Erythrocytes were pretreated with CO, cross-linked with 5 mM DTBP for 1 or 3 h,
      loaded with a solution containing 500 mM glucose for 24 h, and freeze-dried in a
      medium containing 15% (w/v) albumin. Rehydration followed in distilled water.
      Complete recovery, measured as the percentage of free hemoglobin, was achieved
      for cells cross-linked with 5 mM DTBP for 3 h and freeze-dried to a final water
      content of 10-15%. Non-cross-linked cells lysed 100% on rehydration in distilled
      water. No methemoglobin (MetHb) formation as a result of freeze-drying was
      detected in CO-treated cells. In non-CO-treated cells 20% of the Hb was converted
      to MetHb.

PMID- 10924269
TI  - Some observations on the use of cultured corneal endothelial cells as a model for
      intact corneal endothelium.
AB  - Major differences have been identified between corneal endothelial cells in situ
      and those grown in culture. Cells in intact porcine corneal endothelium were
      studied and compared with primary cultures of the same cells either in suspension
      or in monolayers which had been grown on plastic (Nunc, Permonax). Differences
      were identified in the organization of the cytoskeleton (filamentous actin)
      between the cells in situ and in monolayer culture. The ability to withstand
      exposure to cryoprotective concentrations of Me(2)SO also varied substantially
      depending on whether the cells were in situ or in culture. These results
      underline the need for caution in the use of cells in culture as a model for
      studying the nature of injury to cells during the freezing of whole tissues.

PMID- 10924268
TI  - A simple cryopreservation method for the maintenance of cell viability and
      mechanical integrity of a cultured cartilage analog.
AB  - A method for cryopreserving a 100-microm-thick sheet of tissue produced by
      cultured rabbit chondrocytes has been developed. The method maintains cell
      viability and avoids tissue fracture and degradation of mechanical properties. A
      slow-freeze, fast-thaw procedure with 2 M Me(2)SO as the cryoprotectant resulted
      in no tissue fracture and approximately 90% viable cells after storage in culture
      flasks at -80 degrees C. The cells in the retrieved tissue remained responsive to
      IL-1beta, and tensile and fracture toughness properties of the tissue were not
      degraded by cryopreservation.

PMID- 10924270
TI  - Approach to gene therapy of glycogenosis type II (Pompe disease).
AB  - Pompe disease is a generalized lysosomal glycogenosis affecting essentially the
      skeletal muscles and the heart. It is due to the deficiency of acid alpha
      glucosidase, also called acid maltase, involved in glycogen degradation by the
      cleavage of alpha-1,4 and alpha-1,6 glycosidic linkages. The severe infantile,
      milder juvenile, and late-onset or adult forms are associated under the generic
      name of glycogenoses type II. The clinical picture can differ according to these
      variants, forming a clinical spectrum from cardiorespiratory failure with early
      death in the infantile variant to late muscular weakness or respiratory problems
      in the adult variant. Enzymatic pre- and postnatal diagnoses and mutation
      characterization are available. Different therapeutic attempts have been
      conceived and some of them have come to clinical trials. Several pilot studies
      have demonstrated the feasibility of gene therapy and remarkable advances have
      been realized. Of particular interest, strategies for gene therapy in a
      generalized disease like Pompe disease must be accompanied by the secretion and
      uptake of the corrective enzyme by more distant cells or tissues in order to
      obtain efficient results. Preliminary positive results have been obtained in
      animal models, and new approaches with improvements in the access to muscle and
      heart, in the efficacy and innocuity of vectors, and in the clinical evolution
      are proposed. Gene therapy is a promising strategy for Pompe disease. However,
      several steps must be explored before this method becomes clinically successful.

PMID- 10924271
TI  - "Supercharged Cells" for delivery of recombinant human iduronate-2-sulfatase.
AB  - Expression of iduronate-2-sulfatase (IDS) from three different promoters in four
      retroviral vectors was studied in peripheral blood lymphocytes from patients with
      Hunter syndrome (PBL(MPS)), i.e., the LTR in vectors L2SN and L2, avian beta
      actin promoter in LB2, and the CMV early promoter in LNC2. PBL(MPS) were exposed
      to packaging cell supernatant resulting in transduction frequencies ranging 10
      fold from 5 to 49%. Surprisingly, IDS activities were equally high in all
      transduced lymphocyte populations: 515 U/mg/h in PBL(MPS)-L2SN, 734 in PBL(MPS)
      LB2, 352 in PBL(MPS)-L2, and 389 in PBL(MPS)-LNC2 compared to controls (<10 in
      PBL(MPS)-LXSN or PBL(MPS)). The half-life of endocytosed IDS in PBL(MPS) was 1.9
      days. However, the level of lymphocyte IDS activity from proviral expression was
      found to be only a fraction of the total, a large portion being derived from
      reuptake of enzyme from murine packaging cells, i.e., a "second source" of
      enzyme. Therefore, measurement of transgene lysosomal enzyme soon after exposure
      of target cells to vector supernatant may yield a gross overestimate of long-term
      transgene expression by transduced cells. Nevertheless, patient fibroblasts
      cocultured with transduced PBL(MPS) had reduced (35)SO(4)-GAG accumulation,
      levels similar to those of normal fibroblasts. These studies revealed a broadly
      applicable phenomenon: cells can be charged with a lysosomal enzyme to levels
      much higher than those found in nature. By "supercharging" cells with a lysosomal
      protein (or other molecule bearing the mannose-6-phosphate ligand), such cells
      may be exploited as vehicles for systemic delivery of therapeutic or diagnostic
      agents.

PMID- 10924272
TI  - Hyperphenylalaninemia and 7-pterin excretion associated with mutations in 4a
      hydroxy-tetrahydrobiopterin dehydratase/DCoH: analysis of enzyme activity in
      intestinal biopsies.
AB  - Hyperphenylalaninemia, which can cause neurological disorders and mental
      retardation, results from a mutation in phenylalanine hydroxylase or an enzyme
      required for biosynthesis or regeneration of its cofactor, tetrahydrobiopterin.
      The hyperphenylalaninemia variant primapterinuria is characterized by the
      excretion of 7-biopterin (primapterin). This disorder is thought to be due to a
      deficiency of 4a-hydroxy-tetrahydrobiopterin dehydratase (pterin-4a-carbinolamine
      dehydratase), but a lack of tissue activity has not been directly demonstrated.
      The five mutations so far recognized in patients with primapterinuria are
      associated with either a single amino acid change or a premature stop codon. Only
      C81R has been successfully expressed in soluble form, and was found to have 40%
      of normal activity. Tissues which could be obtained by minimally invasive
      procedures were analyzed for dehydratase activity. None was detected in normal
      human white cells or fibroblasts. However, activity was found in intestine of
      rat, dog, pig, and particularly humans where it was only eight times lower than
      in liver. Distribution along the length and across the wall of small intestine
      was relatively uniform. Moreover, the dehydratases from human liver and
      intestinal mucosa have identical kinetic properties. A biopsy of duodenal mucosa
      from a patient with homozygous E96K dehydratase had activity of 55 nmol. min(
      1)g(-1) mucosa compared to 329 +/- 32 nmol. min(-1)g(-1) tissue in controls (n =
      12). The sixfold lower tissue activity of the E96K mutant alone may not be
      sufficient to account for the biochemical symptoms of primapterinuria in this
      patient. However, accumulation of a 4a-hydroxy-tetrahydrobiopterin degradation
      product (a side-chain cyclic adduct), which has been observed in vitro and
      appears to be a dehydratase inhibitor, may further exacerbate the problem.

PMID- 10924273
TI  - Urinary lactate excretion to monitor the efficacy of treatment of type I glycogen
      storage disease.
AB  - The purpose of this study was to investigate the usefulness of urinary lactate
      measurements to assess the adequacy of dietary treatment in patients with type I
      glycogen storage disease (GSD-I). We determined the correlation of urine and
      blood lactate concentrations in 21 GSD-I patients during 24-h admissions to the
      General Clinical Research Center (GCRC) during which hourly blood samples and
      aliquots of every void were obtained. In all but 1 patient, we found a good
      correlation between blood lactate concentrations and urinary lactate excretion.
      One patient did not excrete lactate in significant amounts despite elevated blood
      lactate concentrations. In 17 patients, the highest blood lactate concentrations
      occurred during the night. Markedly elevated nighttime average blood lactate
      concentrations above 3.5 mmol/l resulted in a urinary lactate concentration above
      the normal limit of 0.067 mmol/mmol creatinine in the first morning urine
      specimen. Mildly elevated nighttime blood lactate concentrations (between 2.2 and
      3.5 mmol/l) led to urinary lactate concentrations that were either normal or
      moderately elevated. All patients with normal blood lactate concentrations during
      the night also had normal first morning urinary lactate concentrations. The
      degree of urinary lactate excretion in relation to blood lactate concentrations
      varied by individual. Urinary filter paper specimens, collected at home during
      the night and in the morning and mailed to the laboratory, were used to monitor
      the dietary compliance of 5 GSD-I patients at home over a period of 6 to 9 weeks
      prior to their GCRC admissions. These data suggested variable degrees of dietary
      control. In conclusion, the urinary lactate concentration is a useful parameter
      to monitor therapy of GSD-I patients at home. To be interpretable, the baseline
      urinary lactate concentration in relation to the blood lactate concentration has
      to be determined.

PMID- 10924274
TI  - Deficient ferritin immunoreactivity in tissues from niemann-pick type C patients:
      extension of findings to fetal tissues, H and L ferritin isoforms, but also one
      case of the rare Niemann-Pick C2 complementation group.
AB  - Previous studies employing rabbit polyclonal anti-human liver ferritin have shown
      an absence of L ferritin immunoreactivity in liver and spleen tissue from
      patients with Niemann-Pick disease type C1 (NPC1). The great majority of NPC
      cases is caused by defects of the NPC1 gene, and a minority by those of another
      (NPC2). In this study using polyclonal and monoclonal antibodies we show the
      deficiency of H and L ferritin isoforms in various NPC tissues, including fetal
      NPC1, not previously described. In particular, evidence is provided for
      deficiency in H and L ferritins in tissues, except lung, from a patient with
      Niemann-Pick disease type C2 (NPC2). The present findings indicate that H and L
      ferritins are deficient in both NPC types characterized by accumulation of
      unesterified cholesterol and additional metabolites in the endosomal/lysosomal
      system. We hypothesize that the lesions in NPC1 and NPC2 block the intracellular
      utilization not only of cholesterol, but also that of iron for the synthesis of
      cytosolic ferritin.

PMID- 10924275
TI  - CLN3 protein regulates lysosomal pH and alters intracellular processing of
      Alzheimer's amyloid-beta protein precursor and cathepsin D in human cells.
AB  - Maintenance of the appropriate pH in the intracellular vacuolar compartments is
      essential for normal cell function. Here, we report that CLN3 protein, which is
      associated with the juvenile form of neuronal ceroid lipofuscinosis (JNCL),
      participates in lysosomal pH homeostasis in human cells. We show that CLN3
      protein increases lysosomal pH in cultured human embryonal kidney cells, whereas
      inhibition of CLN3 protein synthesis by antisense approach acidifies lysosomal
      compartments. These changes in lysosomal pH are sufficient to exert a significant
      biological effect and modify intracellular processing of amyloid-beta protein
      precursor and cathepsin D, model proteins whose metabolism is influenced by the
      pH of acidic organelles. Mutant CLN3 protein (R334C) that is associated with the
      classical JNCL phenotype was devoid of biological activities of wild-type CLN3
      protein. These data suggest that the pathogenesis of juvenile neuronal ceroid
      lipofuscinosis is associated with altered acidification of lysosomal
      compartments. Furthermore, our study indicates that CLN3 protein affects
      metabolism of proteins essential for cell functions, such as amyloid-beta protein
      precursor, implicated in Alzheimer's disease pathogenesis.

PMID- 10924276
TI  - Complex association analysis of graves disease using a set of polymorphic
      markers.
AB  - Graves disease is complex autoimmune thyrotoxicosis. A number of genes may
      contribute to the development of the disorder. Some of them may be genes that
      encode cytotoxic T-lymphocyte-associated serine esterase-4 (CTLA4), subunit 2 of
      large multifunctional protease (LMP2), thyroid-stimulating hormone receptor
      (TSHR), and interleukin 1 receptor antagonist (IL1RN). We studied polymorphism of
      Ala17Thr CTLA4, H60R LMP2, Pro52Thr TSHR, and IL1RN-VNTR in healthy controls (n =
      93) and patients with Graves disease (n = 78) using PCR. To study CTLA4, H60R,
      and TSHR polymorphism, PCR products were digested with MboI, Hin6I and PsyI,
      respectively. Comparative analysis using chi(2) test showed significant
      differences in allele and genotype frequency of Ala17Thr polymorphic marker
      between the two groups studied. Thus, the CTLA4 gene may be involved in the
      pathogenesis of Graves disease in a Moscow population.

PMID- 10924277
TI  - Analysis of multiple mutations in the hALG6 gene in a patient with congenital
      disorder of glycosylation Ic.
AB  - Congenital disorder of glycosylation Ic is caused by mutations in the hALG6 gene
      that encodes an alpha-1,3 glucosyltransferase. This enzyme is required for the
      addition of the first glucose residue to the lipid-linked oligosaccharide
      precursor for N-linked glycosylation. Here we describe the biochemical and
      molecular analysis of a patient with three mutations in the hALG6 gene. The
      maternal allele has an intronic G --> A mutation resulting in skipping of exon3
      (IVS3 + 5G > A). This produces a nonfunctional enzyme as shown by its inability
      to restore normal glycosylation in a Saccharomyces cerevisiae strain lacking a
      functional ALG6. The paternal allele has two mutations. One is a deletion of
      three bases (895-897delATA) leading to an in-frame deletion of isoleucine 299
      (delI299) located in a transmembrane domain. The second mutation on the same
      allele 911T > C causes a F304S change. When expressed in the ALG6 deficient yeast
      strain, this allele restores glycosylation but the mRNA is unstable or
      inefficiently transcribed, contributing to the impaired glycosylation in the
      patient.

PMID- 10924278
TI  - Protein binding by the 3' untranslated region of alpha-striated tropomyosin.
AB  - Tropomyosin is a component protein of the thin filament system in striated
      muscle, regulating the interaction between actin and myosin. The 3' untranslated
      region of the alpha-striated tropomyosin gene (TM UTR) induces muscle
      differentiation when expressed in primary fibroblasts, but the mechanism has not
      been defined. We hypothesize that fibroblasts utilize resident proteins to effect
      this response, perhaps by TM UTR binding to protein(s). In order to facilitate
      identification of protein(s) involved in mediating this differentiation response,
      we investigated the potential for this sequence to bind to cellular protein
      utilizing electrophoretic mobility gel shifting analysis (EMSA) with and without
      UV cross-linking. Under very specific conditions (including pH, KCl, and Mg
      concentration and extent of phosphorylation of protein), the TM UTR is able to
      bind protein in cells that differentiate upon TM UTR expression. Protein binding
      is significantly more extensive in cytoplasmic than nuclear protein preparations.
      Secondary structure of the RNA probe facilitates protein binding. The molecular
      masses of bound proteins are approximately 42 and 115 kDa under basal conditions.
      EMSA analysis of extract from cultured skeletal muscle confirms that protein
      binding by the TM UTR occurs in this cell type, and is more extensive in less
      differentiated cells. The demonstration of highly regulated protein binding by
      the TM UTR raises the possibility that this sequence may cause differentiation by
      binding to endogenous proteins, and further that this sequence may play a role in
      normal differentiation. Identification of proteins bound by the TM UTR will be
      necessary to completely define the mechanism by which it causes differentiation.

PMID- 10924279
TI  - Higher proportion of mitochondrial A3243G mutation in blood than in skeletal
      muscle in a patient with cardiomyopathy and hearing loss.
AB  - Phenotypes of individuals with the mitochondrial A3243G mutation and amount of
      mutant DNA in different tissues can be very variable, but the proportion of
      mutant DNA was consistantly lower in blood than muscle in previously studied
      patients. We detected the A3243G mutation in a 54-year-old patient with
      cardiomyopathy and hearing loss, where the amount of mutant DNA was higher in
      blood (19%) than in muscle (6%). This shows that the level of A3243G mutation is
      not always lower in rapidly dividing tissues such as blood than in muscle, as has
      been presumed until now.

PMID- 10924280
TI  - The pathogenic role of point mutations affecting the translational initiation
      codon of mitochondrial genes.
AB  - The mutation T3308C results in a Met --> Thr change at the highly conserved amino
      acid position 1 of the mtDNA ND1 gene (M1T). To study its potential pathogenic
      effect we have carried out a combination of mitochondrial protein synthesis and
      Northern and Western analyses. Our data demonstrate that M1T mutation does not
      affect the efficiency of the synthesis of the ND1 polypeptide and suggest that
      any codon specifying methionine located close to the 5' end of mitochondrial
      mRNAs may be used as translational initiator.

PMID- 10924281
TI  - Pre- and postpartum sex steroids in female marmosets (Callithrix kuhlii): is
      there a link with infant survivorship and maternal behavior?
AB  - Recent studies in primates have suggested that pre- and peripartum sex steroid
      hormones may be important determinants of maternal behavior and motivation, since
      higher levels of prepartum estrogen are associated with maternal competency and
      infant survivorship. To test the cross-species generality of this finding, we
      monitored excreted profiles of estradiol (E(2)), progesterone metabolites
      (pregnanediol glucuronide; PdG), and E(2):PdG ratios throughout pregnancy in
      black tufted-ear marmosets (Callithrix kuhlii). Additionally, we wanted to
      determine the extent to which variability in maternal carrying effort was related
      to hormonal factors and relative levels of maternal experience. For six females,
      hormonal profiles were determined by enzyme immunoassay for two pregnancies, one
      in which infants survived at least 2 weeks postpartum and one in which infants
      did not survive. Our within-subjects analyses revealed significant differences in
      mean prepartum E(2) levels for females in the different infant survival
      conditions. In contrast to previous findings, however, females exhibited
      significantly higher prepartum E(2) levels when their infants did not survive a
      minimum of 2 weeks postpartum, relative to when their infants did survive.
      Maternal carrying effort was also negatively and significantly correlated with
      prepartum E(2) levels. Unlike previous reports in callitrichid primates, then,
      our data suggest that high concentrations of prepartum E(2) in callitrichid
      primates are not necessarily associated with competent maternal behavior and may
      instead be associated with poor infant survivorship and inadequate maternal care.
      Further, our results appear to be convergent with research focusing on human
      mothers and may represent a common underlying mechanism linking prepartum
      estrogen and postpartum affect and behavior in some primates.

PMID- 10924282
TI  - Maternal aggression in endothelial nitric oxide synthase-deficient mice.
AB  - Lactating female rodents protect their pups by expressing fierce aggression,
      termed maternal aggression, toward intruders. Mice lacking the neuronal nitric
      oxide synthase gene (nNOS-/-) exhibit significantly impaired maternal aggression,
      but increased male aggression, suggesting that nitric oxide (NO) produced by nNOS
      has opposite actions in maternal and male aggression. In contrast, mice lacking
      the endothelial nitric oxide synthase gene (eNOS-/-) exhibit almost no male
      aggression, suggesting that NO produced by eNOS facilitates male aggression. In
      the present study, maternal aggression in eNOS-/- mice was examined and found to
      be normal relative to wild-type (WT) mice in terms of the percentage displaying
      aggression, the average number of attacks against a male intruder, and the total
      amount of time spent attacking the male intruder. The eNOS-/- females also
      displayed normal pup retrieval behavior. Because a significant elevation of
      citrulline, an indirect marker of NO synthesis, occurs in neurons of the
      hypothalamus of lactating WT mice in association with maternal aggression, we
      examined the brains of eNOS-/- females for citrulline immunoreactivity following
      an aggressive encounter. The aggressive eNOS-/- females exhibited a significant
      elevation of citrulline in the medial preoptic nucleus and the subparaventricular
      zone of the hypothalamus relative to unstimulated lactating eNOS-/- females.
      Taken together, these results suggest that NO produced by eNOS neither
      facilitates nor inhibits maternal aggression and that NO produced by eNOS has a
      different role in maternal and male aggression.

PMID- 10924283
TI  - Brief refeeding restores reproductive readiness in food-restricted female musk
      shrews (Suncus murinus).
AB  - Food deprivation blocks sexual behavior and disrupts estrous cycles in mammals.
      We asked whether reduced copulatory behavior, produced by limited food intake,
      could be reversed by brief refeeding intervals in the female musk shrew. In
      Experiment 1, animals were food restricted to 60% of ad lib (FR), and an
      additional group of FR females were refed for 90 min prior to testing (RF). Refed
      and ad lib (AL) fed females were significantly more likely to mate than FR
      females. To test the hypothesis that food-induced restoration of copulatory
      behavior is not the result of changes in peripheral steroids, we repeated
      Experiment 1 using ovariectomized and testosterone-implanted females. The results
      from Experiment 2 were similar to those found in the first study. Next, a more
      severe refeeding schedule was employed; females were restricted to 50% of ad lib
      intake. Females in the RF and FR groups were significantly less likely than the
      AL animals to mate. In the last experiment, females were food restricted to 50%
      and longer refeeding intervals were employed. Four and one-half hours of food
      intake did not reinstate sexual behavior, but females refed for 12 h were as
      likely to mate as ad lib fed controls. We also did not detect any differences in
      plasma concentrations of testosterone and cortisol in AL, FR, and RF ovary-intact
      animals. These results define a nutritional threshold for copulatory behavior in
      the musk shrew. Since this species is highly sensitive to small alterations in
      food intake, it is a useful model for studies of interactions between metabolic
      fuels and behavior.

PMID- 10924284
TI  - Salivary cortisol and social status among Dominican men.
AB  - Studies of nonhuman primates indicate that social subordinance associates with
      chronic elevated cortisol, but this finding has not been replicated among humans.
      This topic was examined in a study of 31 healthy adult male Dominican villagers
      ages 17 to 49 years. Each subject's mean cortisol level was calculated using
      multiple time-standardized salivary cortisol samples (minimum = 6, mean = 14. 8
      samples per subject) determined by radioimmunoassay. Semistructured ethnographic
      interviews were used to collect several measures of social status. Data were
      analyzed with a backward stepwise multivariate linear regression model. Partial
      regression statistics revealed four significant associations with cortisol: (i)
      men with reputations for illicit social behavior had higher cortisol; (ii) men
      who reported more frequent distressed mood had higher cortisol; (iii) men rated
      as less trustworthy, agreeable, influential, and helpful by their peers had
      higher cortisol; and (iv) men whose fathers were absent as a childhood caretaker
      had higher cortisol. No associations were found between cortisol and (a) a
      composite of educational attainment, income, and material wealth; (b) frequency
      of tobacco consumption; (c) frequency of perceived social stressors; or (d) a
      composite of number of children and dependents.

PMID- 10924285
TI  - A conspecific attenuates prolactin responses to open-field exposure in rats.
AB  - Acute exposure to a novel environment, such as an open field, generally results
      in a prolactin surge, while several days of exposure to the open field is often
      characterized by a decline in prolactin. As exposure to the open field is a
      psychological stressor, altering the animal's interpretation of the event should
      alter prolactin levels. In the present study, juvenile male and female rats were
      habituated to the open field for 1 or 5 days prior to testing in the chamber
      alone or with a same-sex conspecific. Levels of prolactin were measured across
      all rats, and play (pins) was recorded for animals tested with a conspecific.
      Five days of habituation to the chamber resulted in lower levels of prolactin and
      more play than 1 day of habituation. Across both conditions of habituation,
      testing with a conspecific caused lower levels of prolactin than testing alone.
      In addition, play and prolactin were negatively correlated. The presence of a
      conspecific in a stressful situation may have reduced stress by altering the
      animal's negative interpretation of the open field. Further, as the intensity of
      the social interaction increased (more play), prolactin levels decreased.

PMID- 10924286
TI  - Mouthbrooding in the black-chinned tilapia, Sarotherodon melanotheron (Pisces:
      Cichlidae): the presence of eggs reduces androgen and estradiol levels during
      paternal and maternal parental behavior.
AB  - The black-chinned tilapia (Sarotherodon melanotheron) is considered a paternal
      mouthbrooder in which the male churns the eggs in his mouth for 14-18 days after
      they are fertilized. We previously showed that plasma androgen and estradiol
      concentrations increased significantly between the beginning and end of
      mouthbrooding. Here we provide evidence that androgen and estradiol are
      relatively high in prespawning male tilapia, decrease significantly with the
      initiation of mouthbrooding, and return to and slightly surpass prespawning
      levels by the end of mouthbrooding. We then test the hypothesis that the
      initiation of mouthbrooding causes a decrease in androgen and estradiol. We
      raised single pairs of tilapia in seawater aquaria and conducted two experiments.
      In the first, we removed eggs from males on the morning of Day 1 of
      mouthbrooding, followed changes in plasma androgen and estradiol in the afternoon
      of Day 1 and on Days 6, 11, and 16, and compared them to levels in control males
      who kept their eggs. Removing eggs from mouthbrooding males on the morning of Day
      1 eliminated the decrease in plasma androgen and estradiol observed in the
      afternoon of Day 1 of mouthbrooding. This demonstrates that the eggs are
      necessary for the decrease. We observed that, infrequently, the female of the
      pair would pick up the eggs to brood them in her mouth. In a second experiment,
      in the afternoon of Day 1, we sampled both the male and female of pairs in which
      the female brooded eggs. In female-brooding pairs, the females had significantly
      lower androgen and estradiol levels than prespawning females. The black-chinned
      tilapia in captivity exhibits both paternal and maternal parental behavior. In
      both sexes the initiation of mouthbrooding triggers a decrease in androgen and
      estradiol concentrations. We conclude that the presence of eggs inhibits the
      pituitary-gonadal axis in both males and females and hypothesize that a chemical
      signal from the eggs is delaying the initiation of the next brood.

PMID- 10924287
TI  - Timing of prenatal androgen exposure: anatomical and endocrine effects on
      juvenile male and female rhesus monkeys.
AB  - Prenatal androgen shapes genital differentiation. In humans, genital anatomy
      determines sex of rearing and subsequent behavioral development. Rhesus monkey
      genital anatomy and neuroendocrine function are sexually differentiated, and
      behavioral development occurs in a complex social environment. We investigated
      prenatal hormonal influences on sexual differentiation by suppressing or
      increasing androgens in male and female rhesus monkeys. Pregnant multiparous
      female rhesus monkeys received 35-40 days of testosterone enanthate (TE)
      treatment, androgen antagonist (flutamide, FL) treatment, or vehicle starting on
      gestation day (GD) 35 or 40 (early) or GD 110 or 115 (late). Exogenous androgen
      increased neonatal LH secretion in females when given early and altered female
      genital differentiation when administered either early or late. TE treatment,
      early or late in gestation, had no measurable effects on male genital
      differentiation or neuroendocrine function. Early FL treatment, however,
      radically altered male genital differentiation, producing in two cases males with
      a urethral opening separate from the glans. In females, early FL treatment
      produced detectable alterations in genitalia consistent with a reduced exposure
      to prenatal androgen, suggesting that female rhesus monkeys are naturally exposed
      prenatally to meaningful levels of T. Late FL treatment reduced male penis size
      and increased neonatal T secretion, but had no effect in females. This is the
      first study to block endogenous prenatal testosterone in rhesus monkeys, thereby
      altering sexual differentiation. These findings illustrate the complexity of
      prenatal influences on anatomical and neuroendocrine development. The
      relationship between the anatomical changes reported here and sex differences in
      behavior is currently under investigation.

PMID- 10924288
TI  - Evidence for a mate-attracting chemosignal in the dwarf African clawed frog
      Hymenochirus.
AB  - Many male frogs and toads possess sexually dimorphic skin glands (breeding
      glands). However, in most anuran species, the functional significance of the
      glands is unknown. Here we show that the breeding glands of male dwarf African
      clawed frogs (Hymenochirus sp. ) release a mate-attractant chemosignal. The mate
      attractant activity was assessed using a two-choice aquatic Y-maze. Female
      Hymenochirus were allowed to choose between different treatment waters (e.g.,
      plain water and water housing males) in the upstream arms of the maze, and the
      females' movements were monitored by computer-linked motion sensors. Females
      showed a positive chemotaxis to water housing males and to water containing
      homogenized breeding glands. Females showed no reaction to water housing
      conspecific females or to water housing breeding gland-ablated males. Additional
      choice tests demonstrated that females were more attracted to water housing males
      than to water housing females and to water containing homogenized breeding glands
      than to water housing breeding gland-ablated males. Males in the maze showed no
      response to water housing either females or other males, indicating that the
      attractant is specific for females and is therefore neither a species aggregation
      signal nor a food-related attractant. These results represent the first
      experimental demonstration of a mate-attractant function for anuran breeding
      glands. Because many anuran species possess breeding glands, these results
      suggest that pheromonal communication could be more widespread among frogs and
      toads than previously believed.

PMID- 10924289
TI  - The VA HDL intervention trial: clinical implications.

PMID- 10924290
TI  - Magnesium: an antiarrhythmic drug, but only against very specific arrhythmias.

PMID- 10924291
TI  - Troponin, embolization and restoration of microvascular integrity.

PMID- 10924292
TI  - Post-cardioversion atrial fibrillation: the synthesis of modern concepts?

PMID- 10924293
TI  - CRP: does it stand for C oronary R estenosis P rediction?

PMID- 10924294
TI  - Hospitalization in ICD recipients.

PMID- 10924295
TI  - Management of patients with myocardial infarction and hypertension.

PMID- 10924296
TI  - Manpower in cardiology in Europe. The Cardiology Monospeciality Section of the
      UEMS.
AB  - This is the first systematic survey of cardiology manpower in Europe. Hitherto,
      there has been no published information on the number of cardiologists in the
      different European nations and whether it was growing or stable. Important
      differences in the number of cardiologists and trainees are observed, with the
      highest figures in Greece, Italy and France (more than 80/10(6)inhabitants) and
      the lowest in the Scandinavian nations, Austria, Germany and the U.K. (35 or
      less/10(6)inhabitants). This is partly due to different roles and the activities
      of the cardiologists in these countries as well as their capacity to undertake
      various cardiological procedures. Some comparisons with the U.S.A. and
      projections for the year 2000 are also made.

PMID- 10924297
TI  - Socioeconomic inequalities in cardiovascular disease mortality; an international
      study.
AB  - BACKGROUND: Differences between socioeconomic groups in mortality from and risk
      factors for cardiovascular diseases have been reported in many countries. We have
      made a comparative analysis of these inequalities in the United States and 11
      western European countries. The aims of the analysis were (1) to compare the size
      of inequalities in cardiovascular disease mortality between countries, and (2) to
      explore the possible contribution of cardiovascular risk factors to the
      explanation of between-country differences in inequalities in cardiovascular
      disease mortality. DATA AND METHODS: Data on ischaemic heart disease,
      cerebrovascular disease and total cardiovascular disease mortality by
      occupational class and/or educational level were obtained from national
      longitudinal or unlinked cross-sectional studies. Data on smoking, alcohol
      consumption, overweight and infrequent consumption of fresh vegetables by
      occupational class and/or educational level were obtained from national health
      interview or multipurpose surveys and from the European Union's Eurobarometer
      survey. Age-adjusted rate ratios for mortality were correlated with age-adjusted
      odds ratios for the behavioural risk factors. RESULTS: In all countries mortality
      from cardiovascular diseases is higher among persons with lower occupational
      class or lower educational level. Within western Europe, a north-south gradient
      is apparent, with relative and absolute inequalities being larger in the north
      than in the south. For ischaemic heart disease, but not for cerebrovascular
      disease, an even more striking north-south gradient is seen, with some 'reverse'
      inequalities in southern Europe. The United States occupy intermediate positions
      on most indicators. Inequalities in cardiovascular disease mortality are
      associated with inequalities in some risk factors, especially cigarette smoking
      and excessive alcohol consumption. CONCLUSIONS: Socioeconomic inequalities in
      cardiovascular disease mortality are a major public health problem in most
      industrialized countries. Closing the gap between low and high socioeconomic
      groups offers great potential for reducing cardiovascular disease mortality.
      Developing effective methods of behavioural risk factor reduction in the lower
      socioeconomic groups should be a top priority in cardiovascular disease
      prevention.

PMID- 10924298
TI  - Plasma levels of C-reactive protein after coronary stent implantation.
AB  - AIMS: This study was designed to investigate the role of inflammation on the
      occurrence of angiographic restenosis 6 months after coronary stent implantation
      and the influence of different kinds of antithrombotic and antiplatelet
      strategies on inflammation. METHODS AND RESULTS: In an open randomized trial, 40
      consecutive patients were treated with aspirin (100 mg. day(-1)) and either
      ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and
      dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent
      implantation. Plasma levels of C-reactive protein were determined one day before
      stent implantation and serially thereafter twice daily up to 120 h. C-reactive
      protein plasma levels increased significantly (P<0.0001) after stent
      implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C
      reactive protein plasma levels (P=0.51) or the occurrence of angiographic
      restenosis (P=0.48). C-reactive protein plasma levels were significantly higher
      in patients with lesion type C compared to types A or B (P=0.035), respectively.
      C-reactive protein plasma levels were significantly higher and mean shoulder
      levels occurred 48 h later in patients with restenosis compared to patients
      without restenosis after 6 months (P=0.038). CONCLUSIONS: Elevated C-reactive
      protein plasma levels still persisting 96 h after stent implantation might
      reflect a prolonged inflammatory reaction to coronary stent implantation which
      might causally be involved in pathophysiological mechanisms leading to
      restenosis.

PMID- 10924299
TI  - Cardiovascular risk and therapeutic benefit of coronary interventions for
      patients with unstable angina according to the troponin T status.
AB  - AIMS: Elevation of troponin T in patients with unstable angina is predictive of
      adverse outcomes. Since no advanced therapeutic concept for such high-risk
      patients has been established, we investigated cardiac risk prior to, during, and
      after coronary revascularization in patients with unstable angina stratified
      according to the troponin T status. METHODS AND RESULTS: Out of 351 patients with
      unstable angina, troponin was elevated for 36% of the patients as determined by
      qualitative bedside tests. The patients were followed during hospitalization and
      30 days after discharge for incidence of death and myocardial infarction. In
      troponin-positive patients, clinical symptoms were more refractory to medical
      treatment than in troponin-negative patients (78% vs 44%;P=0.002). Although these
      patients were catheterized earlier (1.6 vs 3.4 days;P=0.005) and more frequently
      (95% vs 69%;P<0.001), troponin-positive patients suffered a higher incidence of
      cardiac events prior to scheduled revascularization (death, myocardial
      infarction; 6.4% vs 0.4%;P<0.001). The angiogram for troponin-positive patients
      confirmed a more severe coronary artery disease requiring revascularization (69%
      vs 50%;P=0.001). Also the following coronary intervention was more complicated
      (death, myocardial infarction; 15.3% vs 4.8%;P=0.02). During the 30-day follow-up
      period, cardiac risk remained elevated for troponin-positive patients.
      CONCLUSIONS: Troponin T rapid testing reliably identified high-risk patients with
      unstable angina. A higher event rate was observed prior to and particularly in
      association with the coronary intervention. Coronary revascularization did not
      abrogate the increased risk of troponin-positive patients during the 30-day
      follow-up.

PMID- 10924300
TI  - Atrial pacing for suppression of early reinitiation of atrial fibrillation after
      successful internal cardioversion.
AB  - AIMS: To evaluate the efficacy of atrial pacing in the suppression of early
      reinitiation of atrial fibrillation after successful internal cardioversion.
      METHODS AND RESULTS: The efficacy of atrial pacing in suppressing early
      reinitiation of atrial fibrillation was studied in 12 of 45 (29%) patients with
      early reinitiation of atrial fibrillation after successful cardioversion. These
      patients were randomized to undergo either repeated defibrillation alone or
      repeated defibrillation followed by high right atrial pacing at 500 ms in a
      crossover fashion. In patients with persistent early reinitiation of atrial
      fibrillation despite atrial pacing at 500 ms and repeated defibrillation, atrial
      pacing at 300 ms was tested. Lastly, if early reinitiation of atrial fibrillation
      persisted, administration of intravenous sotalol (1.5 mg. kg(-1)) was tested.
      Atrial pacing at 500 ms after defibrillation prevented early reinitiation of
      atrial fibrillation in five of 12 (42%) patients, and was significantly more
      effective than repeated defibrillation (0/9 patients, 0%, P<0.05). During atrial
      pacing at 500 ms, the density of atrial premature depolarizations (APDs) was
      significantly decreased (2.4+/-2.4 APDs. min(-1)vs 16.4+/-9.8 APDs. min(-1), P<0.
      05) and the coupling interval of atrial premature depolarization was
      significantly increased (420+/-32 ms vs 398+/-19 ms, P<0.05) as compared to no
      pacing. In the remaining seven (58%) patients, atrial pacing at 500 ms failed to
      prevent early reinitiation of atrial fibrillation, but significantly decreased
      the density of atrial premature depolarization (3.4+/-2.4 APDs. min(-1)vs 14.2+/
      4.8 APDs. min(-1), P<0.05) and delayed the onset of early reinitiation of atrial
      fibrillation (33+/-17s vs 11+/-11 s, P<0.05). Atrial pacing at 300 ms decreased
      the coupling interval of atrial premature depolarization as compared to no pacing
      and during atrial pacing at 500 ms (P<0.05), but without early reinitiation of
      atrial fibrillation suppression. Administration of intravenous sotalol was
      effective in preventing early reinitiation of atrial fibrillation in five of
      seven (71%) patients where pacing failed to suppress early reinitiation of atrial
      fibrillation. CONCLUSION: The results of this study suggest that atrial pacing
      can be useful when combined with transvenous defibrillation in patients with
      early reinitiation of atrial fibrillation.

PMID- 10924301
TI  - The effect of oral magnesium, alone or as an adjuvant to sotalol, after
      cardioversion in patients with persistent atrial fibrillation.
AB  - AIMS: To determine whether magnesium given orally decreases the recurrence rate
      of atrial fibrillation after elective direct current cardioversion of persistent
      atrial fibrillation. METHODS AND RESULTS: Consecutive outpatients were randomized
      to treatment with oral magnesium (10.3 mmol) or placebo twice daily in a double
      blind fashion. Two groups were studied; magnesium study: 170 patients with atrial
      fibrillation persistent for >1 month, scheduled for their first direct current
      cardioversion. No concomitant antiarrhythmic drugs of class I or III were
      allowed. Sotalol and magnesium study: 131 patients with recurrence of persistent
      atrial fibrillation after previous direct current cardioversion, or a history of
      paroxysmal atrial fibrillation, treated with sotalol. Patients were followed
      until recurrence of atrial fibrillation or for at least 6 months. Magnesium
      study: at cardioversion 67 of 85 (79%) in the placebo group and 64 of 85 (75%) in
      the magnesium group had converted to sinus rhythm. At the end of the study, with
      a follow-up of 6 to 42 months, 15% of patients in the placebo group and 19% of
      patients in the magnesium group remained in sinus rhythm (Log rank test: P=0.37).
      Sotalol and magnesium study: pharmacological conversion to sinus rhythm, after
      oral treatment, was achieved in 34 of 131 (26%) patients. Sinus rhythm, with or
      without cardioversion, was restored in 89% and 85% of the patients in the placebo
      and magnesium groups, respectively. At the end of the study, with a follow-up of
      6 to 42 months, 37% of patients in the placebo group and 30% of patients in the
      magnesium group remained in sinus rhythm (Log rank test: P=0.64). CONCLUSION: In
      patients with persistent atrial fibrillation, oral treatment with magnesium alone
      or as an adjuvant to sotalol, does not influence the recurrence rate of atrial
      fibrillation after elective cardioversion.

PMID- 10924303
TI  - ESC news and appointments

PMID- 10924302
TI  - Hospital readmission after transvenous cardioverter/defibrillator implantation; a
      single centre study.
AB  - AIMS: Hospital readmission after implantation of cardioverter/defibrillators has
      a major impact on quality of life and cost-effectiveness in defibrillator
      patients. Rehospitalization has not been studied in large patient populations
      with modern transvenous defibrillation systems. METHODS AND RESULTS: We report on
      incidence, reasons, time in follow-up, duration and predictors of hospital
      readmission in 180 patients after transvenous implantation of a
      cardioverter/defibrillator during a follow-up period of 25+/-18 months. There
      were 156 readmissions in 79 patients with a 0.87 readmission rate per patient
      during the time followed, a 0.46 readmission rate per patient-year of follow-up
      and a 0.38 readmission rate per patient-year of follow-up for cardiac reasons.
      The majority of readmissions was caused by multiple appropriate shock
      interventions (26%), battery depletion (19%) and lead- and device-related
      complications (14%). The time to first hospital readmission was 12+/-9 months for
      arrhythmia-related and 20+/-16 months for other cardiac-related reasons (P<0.05),
      and could not be predicted by clinical variables, respectively. The duration of
      rehospitalization was 14+/-15 days for cardiac-related reasons and 12+/-17 days
      for arrhythmia-related reasons. Age >60 years was an independent predictor of
      rehospitalization time per patient-year of follow-up for both cardiac-related
      (P<0.005) and arrhythmia-related reasons (P<0.05). CONCLUSION: The rate of
      hospital readmission per patient-year of follow-up is as high as 0.46 after
      implantation of a modern cardioverter/defibrillator. Rehospitalization time in
      such patients is significantly longer in the patient cohort >60 years. The
      majority of readmissions is caused by multiple appropriate shock treatments.
      Further studies are needed to systematically investigate strategies for the
      prevention of rehospitalization in modern ICD therapy.

PMID- 10924304
TI  - The european society of cardiology into the next decade.

PMID- 10924305
TI  - Impact factor of the European Heart Journal.

PMID- 10924306
TI  - Dofetilide for the treatment of atrial fibrillation in patients with congestive
      heart failure.

PMID- 10924307
TI  - Atrial fibrillation: a growth industry in the 21st century.

PMID- 10924308
TI  - Hearts 'too bad' to survive 'too good' to die.

PMID- 10924309
TI  - Ventricular pacing: a promising new therapeutic strategy in heart failure. For
      whom?

PMID- 10924310
TI  - Beta-blockers, ventricular arrhythmias, and sudden death in heart failure: not as
      simple as it seems.

PMID- 10924311
TI  - The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs:
      clinical and regulatory implications. Report on a policy conference of the
      European Society of Cardiology.

PMID- 10924312
TI  - Congenital and acquired long QT syndrome.

PMID- 10924313
TI  - Prognostic value of the presence and development of atrial fibrillation in
      patients with advanced chronic heart failure.
AB  - AIMS: To examine whether the presence, or development, of atrial fibrillation in
      patients with advanced chronic heart failure, is associated with a poorer
      prognosis, compared to patients with sinus rhythm and chronic heart failure.
      METHODS AND RESULTS: We examined 409 patients with moderate to severe chronic
      heart failure, and compared patients with sinus rhythm (n=325) to those with
      atrial fibrillation (n=84). At baseline, the two groups were similar regarding
      most indices of severity of chronic heart failure, such as left ventricular
      ejection fraction (0.23) and New York Heart Association (NYHA) functional class,
      while they were different for age (70 years for atrial fibrillation vs 67 years
      for sinus rhythm patients), aetiology of chronic heart failure, blood pressure,
      concomitant treatment, and plasma neurohormones (all P<0.05). During a mean
      follow-up of 3.4 years (range 2.0-5.4), 203 patients (50%) died. The majority of
      deaths was due to progressive chronic heart failure (55%) or was sudden (28%),
      but there was no difference in mode of death between sinus rhythm and atrial
      fibrillation patients. Overall mortality was higher in atrial fibrillation
      patients (60%), than in those with sinus rhythm (47%; risk ratio 1.40, 95% CI
      1.01-1.92, P=0. 04). After adjusting for important prognostic variables, such as
      age, left ventricular ejection fraction, NYHA class, renal function, and blood
      pressure, the presence of atrial fibrillation was no longer related to increased
      mortality (risk ratio 0.86, range 0.59-1.24, P=ns). Of the 325 patients who had
      sinus rhythm at baseline, 30 (9%) developed atrial fibrillation during the study.
      These patients were older (70 vs 66 years, P<0.007), and had slightly lower blood
      pressure and plasma norepinephrine concentrations (P<0.05), but were otherwise
      similar. During follow-up, mortality was similar in these two groups (47% in
      those with new onset atrial fibrillation, vs 47% in those who had sinus rhythm
      throughout the study). CONCLUSIONS: The present data do not support the concept
      that the presence, or the development of atrial fibrillation in patients with
      advanced chronic heart failure is independently related to an adverse outcome
      during long-term follow-up. The generally observed higher mortality in patients
      with atrial fibrillation thus seems to be related to other factors, associated
      with atrial fibrillation.

PMID- 10924314
TI  - How many people with heart failure are appropriate for biventricular
      resynchronization?
AB  - AIMS: Increasing evidence exists suggesting that biventricular pacing improves
      outcome and symptoms in severe heart failure if various selection criteria are
      fulfilled. It is unsure how many people might benefit from this therapy. Our aim
      was to provide such data. METHODS AND RESULTS: Over one calendar year all
      patients admitted to a large U.K. District General Hospital, that were classified
      with a diagnosis of heart failure, were audited. The selection criteria were; (1)
      severe heart failure (NYHA class III or IV), (2) heart failure due to a dilated
      cardiomyopathy, (3) QRS duration greater than 120 ms or (4) the presence of a
      bundle branch block pattern. Subjects were divided into those in sinus rhythm to
      determine those who would be suitable for atrially synchronized biventricular
      pacing and those with an abnormally long PR interval (>210 ms) who might
      additionally benefit from improved atrioventricular synchrony. 1042 patients were
      coded with heart failure. 721 fulfilled diagnostic criteria and were studied. 202
      (28%) had severe heart failure, 178 (25%) had a QRS of at least 120 ms, 437 (61%)
      had an ischaemic cardiomyopathy, 176 (24%) an idiopathic cardiomyopathy and 433
      (60%) were in sinus rhythm. Overall mortality at the time of census was 29%. 43
      patients were suitable for biventricular pacing with a further 29 atrial patients
      fibrillation who might benefit from biventricular pacing alone. CONCLUSION: Using
      our criteria, approximately 10% of an unselected group of heart failure admitted
      to a typical U.K. district general hospital over a calendar year would be
      appropriate for biventricular pacing. This represents a large number of patients
      who might derive benefit from this new therapy.

PMID- 10924316
TI  - Efficacy of carvedilol on complex ventricular arrhythmias in dilated
      cardiomyopathy: double-blind, randomized, placebo-controlled study.
AB  - AIMS: The aim of the present study was to investigate whether the addition of
      carvedilol to conventional therapy in dilated cardiomyopathy patients is
      associated with further benefits in the treatment of complex non-sustained
      ventricular arrhythmias (Lown class III, IV or V). METHODS AND RESULTS: We
      recruited 168 patients with ischaemic or idiopathic dilated cardiomyopathy, with
      complex ventricular arrhythmias. Patients able to tolerate low doses of
      carvedilol were randomized to treatment with carvedilol or placebo for 6 months.
      Carvedilol treatment improved ventricular function and reduced the incidence of
      arrhythmic episodes. Notably, by the end of the first month of treatment, the
      antiarrhythmic efficacy of the drug was significantly greater in patients with
      ischaemic than in those with idiopathic dilated cardiomyopathy, an effect that
      could probably be attributed to the anti-ischaemic properties of carvedilol.
      After 3 months, at a time when ejection fraction was significantly improved in
      all treated patients, the antiarrhythmic efficacy of carvedilol was similar in
      the two study groups. CONCLUSIONS: Carvedilol antiarrhythmic efficacy was
      paralleled by the improvement in ejection fraction, independent of the aetiology
      of heart failure. The possibility of adding to an already 'optimized'
      conventional therapy a drug able to reduce the incidence of complex non-sustained
      ventricular arrhythmias is a therapeutic option that should be considered in the
      treatment of these patients.

PMID- 10924315
TI  - Experiences from treatment of out-of-hospital cardiac arrest during 17 years in
      Goteborg.
AB  - AIMS: To describe changes in different factors at resuscitation and survival in a
      17-year survey of patients suffering from out-of-hospital cardiac arrest. METHOD:
      The investigation was carried out in the community of Goteborg with 450 000
      inhabitants during 1981-1997 on all patients suffering out-of-hospital cardiac
      arrest in whom resuscitation was attempted. RESULTS: The number of cases per
      year, the proportion of witnessed arrests and the proportion of arrests of
      cardiac aetiology remained similar over time. There was an increase in median age
      from 68 to 73 years (P<0.0001), in the proportion of females from 27% to 33%
      (P=0.035) and in the proportion of patients receiving bystander cardiopulmonary
      resuscitation from 14% to 28% (P<0.0001) with time. There was a shortening of the
      median interval from collapse until defibrillation from 9 min to 6 min (P<0.0001)
      over time but a decrease in the occurrence of ventricular fibrillation as the
      initially recorded arrhythmia from 39% to 32% (P=0.022). There was an increase in
      the proportion of patients having a bystander witnessed cardiac arrest of cardiac
      aetiology being hospitalized alive from 32% to 45% (P<0. 0001 for change over
      time). The proportion of patients discharged alive from hospital increased from
      16% to 29% until 1993, but thereafter decreased to 13% in 1997 (P=0.002 for
      change over time). CONCLUSION: In a survey covering 17 years of resuscitation of
      out-of-hospital cardiac arrest patients we found that the occurrence of
      ventricular fibrillation as the initially recorded arrhythmia decreased. There
      was an increase in age, in the proportion of females and in the use of bystander
      cardiopulmonary resuscitation. The interval between collapse and defibrillation
      was shortened. Survival changed over time with an increase until 1993 but with a
      decrease thereafter.

PMID- 10924318
TI  - ESC news and appointments

PMID- 10924317
TI  - Comparison of intravenously administered dofetilide versus amiodarone in the
      acute termination of atrial fibrillation and flutter. A multicentre, randomized,
      double-blind, placebo-controlled study.
AB  - AIMS: This study compared the efficacy and safety of intravenous dofetilide with
      amiodarone and placebo in converting atrial fibrillation or flutter to sinus
      rhythm. METHODS AND RESULTS: One hundred and fifty patients with atrial
      fibrillation or flutter (duration range 2 h-6 months) were given 15-min
      intravenous infusions of 8 microg. kg(-1)of dofetilide (n=48), 5 mg. kg(-1)of
      amiodarone (n=50), or placebo (n=52) and monitored continuously for 3 h. Sinus
      rhythm was restored in 35%, 4%, and 4% of patients, respectively (P<0.001,
      dofetilide vs placebo;P=ns, amiodarone versus placebo). Dofetilide was more
      effective in atrial flutter than in atrial fibrillation (cardioversion rates 75%
      and 22%, respectively;P=0.004). The mean time to conversion with dofetilide was
      55+/-15 min. Dofetilide prolonged the QTc interval (+16% at 20 min). Amiodarone
      substantially decreased the ventricular rate in non-converters (-18 beats. min(
      1)at 30 min). Two patients given dofetilide (4%) had non-sustained ventricular
      tachycardias, and four (8%) had torsade de pointes, in one case requiring
      electrical cardioversion. CONCLUSION: Intravenous dofetilide is significantly
      more effective than amiodarone or placebo in restoring sinus rhythm in patients
      with atrial fibrillation or flutter. However, when infused intravenously at this
      dose and rate, dofetilide causes a significant incidence of torsade de pointes.

PMID- 10924319
TI  - Regulation of leptin release by mammalian adipose tissue.

PMID- 10924320
TI  - Transcription factor NF-kappaB signals antianoikic function of trefoil factor 3
      on intestinal epithelial cells.
AB  - Transcription factor NF-kappaB has both pro-apoptotic and anti-apoptotic
      properties depending on the cell type. Its role in the intestinal epithelial cell
      has not been well elucidated. Trefoil factor 3 (TFF3) is an anti-apoptotic
      peptide secreted by intestinal goblet cells. Here we show that TFF3 activated NF
      kappaB p50/p65 heterodimer within 1 h in IEC-18 cells (a nontransformed rat
      intestinal epithelial cell line). Moreover, we found that TFF3-treated IEC-18
      cells are resistant to anoikis, an anchorage-related apoptosis in epithelium. In
      addition, the stable expression of a mutant form of the endogenous NF-kappaB
      inhibitor (IkappaBalpha(mut)) in IEC-18 cells results in a significant
      attenuation of anti-anoikic effect of TFF3. Taken together, these data indicate
      that (1) TFF3 is an endogenous gastrointestinal peptide with anti-anoikic
      property; (2) TFF3 activates NF-kappaB in enterocytes; and (3) TFF3-induced
      resistance to anoikis in intestinal epithelial cells is mediated by a distinct
      signaling cascade linked to NF-kappaB. Furthermore, our study implicates NF
      kappaB as an important regulator in survival pathway of intestinal epithelial
      cells.

PMID- 10924321
TI  - Elevated expression and activity of protein-tyrosine phosphatase 1B in skeletal
      muscle of insulin-resistant type II diabetic Goto-Kakizaki rats.
AB  - We investigated the cellular mechanism(s) of insulin resistance associated with
      non-insulin dependent diabetes mellitus (NIDDM) using skeletal muscles isolated
      from non-obese, insulin resistant type II diabetic Goto-Kakizaki (GK) rats, a
      well known genetic rat model for type II diabetic humans. Relative to non
      diabetic control rats (WKY), insulin-stimulated insulin receptor (IR)
      autophosphorylation and insulin receptor substrate-1 (IRS-1) tyrosine
      phosphorylation were significantly inhibited in GK skeletal muscles. This may be
      due to increased dephosphorylation by a protein tyrosine phosphatase (PTPase).
      Therefore, we measured skeletal muscle total PTPase and PTPase 1B activities in
      the skeletal muscles isolated from control rats (WKY) and diabetic Goto-Kakizaki
      (GK) rats. PTPase activity was measured using a synthetic phosphopeptide,
      TRDIY(P)ETDY(P)Y(P)RK, as the substrate. Basal PTPase activity was 2-fold higher
      (P < 0.001) in skeletal muscle of GK rats when compared to WKY. Insulin infusion
      inhibited skeletal muscle PTPase activity in both control (26.20% of basal, P <
      0.001) and GK (25.35% of basal, P < 0.001) rats. However, PTPase activity in
      skeletal muscle of insulin-stimulated GK rats was 200% higher than hormone
      treated WKY controls (P < 0.001). Immunoprecipitation of PTPase 1B from skeletal
      muscle lysates and analysis of the enzyme activity in immunoprecipitates
      indicated that both basal and insulin-stimulated PTPase 1B activities were
      significantly higher (twofold, P < 0.001) in skeletal muscle of diabetic GK rats
      when compared to WKY controls. The increase in PTPase 1B activity in diabetic GK
      rats was associated with an increased expression of the PTPase 1B protein. We
      concluded that insulin resistance of GK rats is accompanied atleast by an
      abnormal regulation of PTPase 1B. Elevated PTPase 1B activity through enhanced
      tyrosine dephosphorylation of the insulin receptor and its substrates, may lead
      to impaired glucose tolerance and insulin resistance in GK rats.

PMID- 10924322
TI  - Identification of a potential nurr1 response element that activates the tyrosine
      hydroxylase gene promoter in cultured cells.
AB  - Expression of the gene encoding tyrosine hydroxylase (TH), the initial and rate
      limiting enzyme of catecholamine biosynthesis, is regulated at the
      transcriptional level during neuronal development and in response to a variety of
      environmental stimuli. Nur-related factor 1 (Nurr1), a member of the orphan
      nuclear receptor superfamily, is required for development of dopamine-producing
      neurons in the ventral midbrain and for expression of TH in these neurons. In the
      present study, we found a direct activation of the rat TH gene promoter by Nurr1
      in cultured cell lines. This activation appeared to be dependent on multiple
      regulatory elements conferring Nurr1 responsiveness to the promoter. We
      identified a Nurr1 response element (TH-NBRE1) in the proximal region of the TH
      promoter that mediates a moderate activation of the promoter. The sequence of TH
      NBRE1 was highly homologous to that of the typical NGFI-B response element. Our
      findings suggest that Nurr1 may be implicated in the transcriptional control of
      TH gene expression during development or in response to altered physiological
      states.

PMID- 10924323
TI  - Differential redistribution of protein kinase C isoforms by cyclic AMP in HL60
      cells.
AB  - In this study we have analyzed the distribution of protein kinase C isoforms in
      cytosol, membrane, and nucleus in HL60 cells. Furthermore, we have studied the
      redistribution of these isoforms after cyclic AMP treatment. Protein kinase C
      localization and cyclic AMP-induced translocation was demonstrated by Western
      blot analysis. Cytosol, membrane and nucleus in HL60 cells expressed the
      abundance of protein kinase C alpha, betaI, betaII, delta, lambda, and zeta
      isoforms. After cyclic AMP treatment, the amount of protein kinase C betaI and
      zeta increased only in the nucleus, while protein kinase C delta increased in the
      three fractions tested. These effects were dependent on the cyclic AMP
      concentration and duration of action. Our results suggest the existence of cross
      talk between the cyclic AMP system and protein kinase C in HL60 cells. Taking
      into account the processes regulated by protein kinase C, these findings also
      suggest that cyclic AMP plays a regulatory role in various cellular responses in
      HL60 cells, such as differentiation and gene expression. The increase observed in
      PKC delta was due to cyclic AMP-dependent protein kinase C activation, and the
      synthesis of enzyme was probably activated by the nucleotide.

PMID- 10924324
TI  - Epigallocatechin gallate inhibits histamine release from rat basophilic leukemia
      (RBL-2H3) cells: role of tyrosine phosphorylation pathway.
AB  - Some tea polyphenolic compounds including (-)-epigallocatechin gallate (EGCG)
      have been shown to inhibit histamine release from mast cells through poorly
      understood mechanisms. By using a mast cell model rat basophilic leukemia (RBL
      2H3) cells we explored the mechanism of the inhibition. EGCG inhibited histamine
      release from RBL-2H3 cells in response to antigen or the calcium-ionophore
      A23187, while (-)-epicatechin (EC) had little effect. Increased tyrosine
      phosphorylation of several proteins including approximately 120 kDa proteins
      occurred in parallel with the secretion induced by either stimulation. EGCG also
      inhibited tyrosine phosphorylation of the approximately 120-kDa proteins induced
      by either stimulation, whereas EC did not. The tyrosine kinase-specific inhibitor
      piceatannol inhibited the secretion and tyrosine phosphorylation of these
      proteins induced by either stimulation also. Further analysis showed that the
      focal adhesion kinase pp125(FAK) was one of the approximately 120-kDa proteins.
      These findings suggest that EGCG prevents histamine release from mast cells
      mainly by inhibiting tyrosine phosphorylation of proteins including pp125(FAK).

PMID- 10924325
TI  - Selective inhibition by alpha-tocopherol of vascular cell adhesion molecule-1
      expression in human vascular endothelial cells.
AB  - An early event in atherogenesis is the adhesion of monocytes to endothelium via
      adhesion molecules such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1).
      It has been suggested that VCAM-1 plays a very important role in recruitment of
      monocytes in atherosclerosis. Several studies suggest that vitamin E has
      antiatherosclerotic properties. However, the mechanism of its antiatherogenic
      effect awaits elucidation. The aim of our study was to evaluate whether alpha
      tocopherol can influence expression of endothelial cell adhesion molecules and
      endothelial adhesiveness. The study was performed on cultured human umbilical
      vein endothelial cells (HUVEC). HUVEC were pretreated with alpha-tocopherol (50
      micromol/l) in different times before stimulation with TNFalpha (100 U/ml) or IL
      1beta (100 U/ml). Protein expression of VCAM-1 and ICAM-1 was measured by flow
      cytometry. mRNA expression of VCAM-1 was measured by reverse transcription
      polymerase chain reaction (RT-PCR). alpha-Tocopherol time dependently reduced
      agonist-induced VCAM-1 in both surface protein (about 40%, 48 h) and mRNA (about
      35%, 48 h) expression in HUVEC but not ICAM-1 surface protein expression.
      Inhibitory effect of alpha-tocopherol was dependent on culture condition of
      HUVEC. Decreased VCAM-1 expression was associated with reduction (about 40%) of
      adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear
      leukocytes (PBMC). Our results suggest that the antiatherogenic effect of alpha
      tocopherol may in part be due to a downregulation of VCAM-1 expression.

PMID- 10924327
TI  - Imipramine inhibits Cl(-) secretion by desensitization of beta-adrenergic
      receptors in calu-3 human airway cells.
AB  - Recent investigations have found that tetracyclic antidepressants like imipramine
      (IMP) have high-affinity sites not only in brain but also in mammalian lung. In
      the present study, we examined the effects of IMP on the Cl(-) secretion produced
      by isoproterenol (ISP), a beta-adrenergic receptor (beta-AR) agonist, in Calu-3
      human airway cells. ISP applied in the basolateral solution generated a sustained
      short-circuit current that was abolished by diphenylamine-2-carboxylate, a Cl(-)
      channel blocker. IMP (0.01-1 mM) applied in the apical or basolateral solution
      for 30 min significantly inhibited the ISP-induced responses in a concentration
      dependent manner, and the inhibitory effects of this drug were remarkable when
      applied from the apical rather than the basolateral side. ISP-induced responses
      were mimicked by forskolin- and 8-bromo-cyclic AMP-induced ones, but which were
      insensitive to IMP. These results indicate that IMP desensitizes the beta-AR on
      the basolateral membrane from the cytosolic side in Calu-3 cells.

PMID- 10924326
TI  - Glucagon-like peptide 1 increases glucose-dependent activity of the homeoprotein
      IDX-1 transactivating domain in pancreatic beta-cells.
AB  - Both glucose and glucagon-like peptide 1 (GLP-1) stimulate insulin gene
      transcription in endocrine pancreatic beta-cells within the islets of Langerhans.
      The effects of glucose are mediated by the homeodomain transcription factor islet
      duodenum homeobox -1 (IDX-1) that binds to two adenine thymidine-rich (A1 and
      A2/3) motifs within the rat insulin promoter. Glucose stimulates the activity of
      the transactivation domain of IDX-1 that lies within the first 80 amino acids of
      the IDX-1 protein. The effects of GLP-1 on insulin gene expression are primarily
      conferred by the cAMP responsive element (CRE) within the insulin promoter. GLP-1
      stimulates glucose-dependent insulin release from beta-cells. We hypothesize that
      GLP-1 may augment the effects of glucose on insulin gene transcription. Here we
      show that GLP-1 stimulates insulin gene transcription independent of the CRE and
      is glucose-dependent. Furthermore, we show that GLP-1 stimulates the
      transactivational activity of IDX-1.

PMID- 10924328
TI  - Kinetics of biodegradation of p-nitrophenol by different bacteria.
AB  - Three bacterial species, i.e., Ralstonia sp. SJ98, Arthrobacter protophormiae
      RKJ100, and Burkholderia cepacia RKJ200, have been examined for their efficiency
      and kinetics behavior toward PNP degradation. All the three bacteria utilized PNP
      as the sole source of carbon, nitrogen, and energy. The rates of radiolabeled [U
      (14)C]PNP degradation by all the bacteria were higher in the nitrogen-free medium
      compared to the medium with nitrogen. The apparent K(m) values of PNP degradation
      by SJ98, RKJ100, and RKJ200 were 0.32, 0.28, and 0.23 mM, respectively, as
      determined from the Michaelis-Menten curves. The maximum rates of PNP degradation
      (V(max)) according to Lineweaver-Burk's plots were 11.76, 7.81, and 3.84 micromol
      PNP degraded/min/mg dry biomass, respectively. The interpretation drawn from the
      Lineweaver-Burk's plots showed that the PNP degradation by SJ98 was stimulated by
      4-nitrocatechol and 1, 2,4-benzenetriol. Benzoquinone and hydroquinone inhibited
      PNP degradation by RKJ100 noncompetitively and competitively, respectively,
      whereas in the case of RKJ200, benzoquinone and hydroquinone inhibited PNP
      degradation in an uncompetitive manner. beta-Ketoadipate did not affect the rate
      of PNP degradation in any case.

PMID- 10924329
TI  - Substrate-dependent lipolysis induced by isoproterenol.
AB  - The relationship between isoproterenol-induced lipolysis and the phosphorylation
      of perilipin and hormone-sensitive lipase (HSL) was examined using cell-free
      systems consisting of lipid droplets isolated from rat fat cells and HSL, and/or
      trioleoylglycerol emulsified with gum arabic and HSL. Isoproterenol was found to
      stimulate lipolysis in the cell-free system with the lipid droplets without an
      increase in the phosphorylation of either perilipin or HSL. On the other hand, no
      stimulation of lipolysis was found in the cell-free system containing lipid
      droplets despite increases in the phosphorylation of perilipin and HSL. In the
      cell-free system consisting of trioleoylglycerol emulsified with gum arabic and
      HSL, neither isoproterenol nor increases in the phosphorylation of perilipin and
      HSL accelerated lipolysis. These results suggest that isoproterenol-induced
      lipolysis may not be mediated through the phosphorylation of perilipin and HSL,
      and may rather be dependent on the substrate of HSL.

PMID- 10924330
TI  - Nitric oxide stimulates tyrosine phosphorylation of p125(FAK) and paxillin in rat
      pancreatic acini.
AB  - Some of the effects of several oncogenes, integrins, growth factors, and
      neuropeptides are mediated by tyrosine phosphorylation of the non-receptor
      tyrosine kinase p125(FAK) and the cytoskeletal protein paxillin. We have
      demonstrated that different stimuli cause tyrosine phosphorylation of p125(FAK)
      and paxillin in rat pancreatic acini. The aim of the present study was to
      determine whether exogenous NO activates this pathway. We demonstrate that in
      isolated rat pancreatic acini, a NO donor, sodium nitroprusside (SNP) stimulates,
      in a dose- and time-dependent way, tyrosine phosphorylation of p125(FAK) and
      paxillin. The same effects could be observed after incubating acini with 8-Br
      cGMP. Moreover, the stimulation caused by SNP was completely abolished by two
      different guanylyl cyclase inhibitors, methylene blue, and LY-83583. These
      inhibitors also diminished unstimulated phosphorylation of p125(FAK) and
      paxillin. We conclude that in rat pancreatic acini exogenous NO causes p125(FAK)
      and paxillin tyrosine phosphorylation that is mediated by a guanylyl cyclase
      dependent pathway.

PMID- 10924331
TI  - The 3' UTR of human MnSOD mRNA hybridizes to a small cytoplasmic RNA and inhibits
      gene expression.
AB  - Human MnSOD localizes to the mitochondria and plays a key protective role by
      detoxifying oxygen free radicals. The MnSOD mRNA 3' UTR contains a 280-bp region
      (Alu-like element or Alu-E) that shows high homology to human Alu and 7SL
      sequences. MnSOD 3' UTR probes hybridize to a specific cytoplasmic RNA species of
      approximately 300 nucleotides. This antisense RNA is most likely 7SL RNA based on
      its size, ubiquitousness, high levels, and lack of inducibility. Hybridization of
      this small RNA to the MnSOD 3' UTR may modulate posttranscriptional MnSOD gene
      expression. This regulation could occur by several means including inhibition of
      translation and mRNA destabilization. Regulation at the level of translational
      initiation does not seem to occur as MnSOD mRNA containing the Alu-E is
      efficiently bound by ribosomes. To test the role of the MnSOD 3' UTR, and in
      particular the Alu-E in gene expression, luciferase reporter gene constructs were
      made containing various regions of the MnSOD 3' UTR including the Alu-E. These
      constructs were transfected into human A549 lung carcinoma cells and luciferase
      activity was measured. Reporter constructs containing the MnSOD 3' UTR and the
      Alu-E repress luciferase activity. Taken together, these results suggest that
      naturally occurring antisense RNA may bind MnSOD mRNA and repress its expression.
      These results also suggest that other mRNAs containing Alu elements may be
      similarly repressed.

PMID- 10924332
TI  - Induction of oxidative stress in leukocytes by an Enterobacter cloacae toxin able
      to form oligomers and binding to proteins.
AB  - A leukotoxic and hemolytic toxin was purified from cultures of Enterobacter
      cloacae. Stimulation of oxidative stress was observed and the production of
      reactive oxidant species was measured in leukocytes treated with toxin by means
      of nitroblue tetrazolium and chemiluminescence assays. Molecular weight of toxin
      was estimated by chromatography and SDS-PAGE. Two protean peaks with toxic
      activity were found in Sephadex G-100 (P1, 42.0 kDa; and P2, 13.3 kDa). The
      relative amounts between the peaks (P1/P2 = 0.36) changed when 2-mercaptoethanol
      was employed (P1/P2 = 0.59). When Sephadex G-200 chromatography was performed, a
      protean peak of Ve = 113 mL (100 kDa) was found; its was dissociated with 3 M
      urea in toxic proteins of lower mass: 42, 27, and 13.3 kDa. SDS-PAGE (15%) showed
      a single toxin band of purified monomer (13.3 kDa), but electrophoresis of a 42
      kDa toxin with urea presented three bands of trimer, dimer, and monomer. An
      increase of casein hydrolysate and albumin molecular weight was observed by
      chromatography after incubation with toxin due to the binding of both proteins
      with toxin.

PMID- 10924333
TI  - The cysteine- and glycine-rich LIM domain protein CRP2 specifically interacts
      with a novel human protein (CRP2BP).
AB  - We used the interaction trap to isolate a novel human protein that specifically
      interacts with the double LIM domain protein CRP2. This protein, designated
      CRP2BP (for CRP2 binding partner), was previously postulated by sequencing
      contigs of human chromosome 20. The observed interaction is mediated via the LIM1
      domain of CRP2 and is of functional relevance in cellular environment. This novel
      single copy gene spans approximately 45-bp and is organized into at least ten
      exons. CRP2BP is expressed in all human tissues tested, with a major mRNA of 4-kb
      in size and an additional 3.2-kb transcript in placenta.

PMID- 10924334
TI  - Apoptosis induced by gp120 in the neocortex of rat involves enhanced expression
      of cyclooxygenase type 2 and is prevented by NMDA receptor antagonists and by the
      21-aminosteroid U-74389G.
AB  - The effects of a single dose of the HIV-1 coat protein gp120 given into one
      lateral cerebral ventricle (i.c.v.) on the expression of cyclooxygenase type 2
      (COX-2) and PGE(2) levels have been studied using Western blotting and ELISA
      techniques applied to brain tissue extracts obtained from the neocortex of
      individual rats, one of the regions of the central nervous system where the viral
      protein causes apoptosis. The results demonstrate that COX-2 expression is almost
      doubled 6 h after a single dose (100 ng) of gp120 and this is paralleled by a
      statistically significant elevation of PGE(2). Enhanced COX-2 expression is
      implicated in the mechanisms of apoptosis evoked by gp120 because the latter is
      prevented by NS398 (10 mg/kg i.p.), a selective inhibitor of COX-2 activity.
      Protection is also afforded by NMDA receptor antagonists, such as MK801 (0.3
      mg/kg i.p.) and CGP040116 (10 mg/kg i.p.), and by the free radical scavenger, U
      74389G (10 mg/kg i.p.), supporting a glutamate-mediated, excitotoxic, mechanism
      of apoptotic death induced by gp120. These data together with the observation
      that MK801 failed to prevent gp120-enhanced COX-2 expression indicate that
      products of the arachidonic cascade may be responsible for elevation of synaptic
      glutamate leading neocortical cells to oxidative stress and excitotoxic
      apoptosis.

PMID- 10924335
TI  - The analysis of nucleotide substitutions, gaps, and recombination events between
      RHD and RHCE genes through complete sequencing.
AB  - We determined the entire nucleotide sequences of all introns within the RHD and
      RHCE genes by amplifying genomic DNA using long PCR methods. The RHD and RHCE
      genes were 57,295 and 57,831 bp in length, respectively. Aligning both genes
      revealed 138 gaps (insertions and deletions) below 100 bp, 1116 substitutions in
      all introns and all exons (coding region), and 5 gaps of over 100 bp. Homologies
      (%) between the RH genes were 93.8% over all introns and coding exons and 91.7%
      over all exons and introns. Various short tandem repeats (STRs) and many
      interspersed nuclear elements were identified in both genes. The proportions of
      Alu sequences in the RHD and RHCE genes were 25.9 and 25.7%, respectively and
      these Alu sequences were concentrated in several regions. We confirmed multiple
      recombinations in introns 1 and 2. Such multiple recombination, which probably
      arose due to the concentrations of Alu sequences and the high level of the
      homology (%), is one of most important factors in the formation and evolution of
      RH gene. The variability of the Rh system may be generated because of these
      features of RH genes. Apparent mutational hotspots and regions with low of K
      values (the numbers of substitutions per nucleotide site) caused by
      recombinations as well as true mutational hotspots may be found in human genome.
      Accordingly, in searching for and identifying single nucleotide polymorphisms
      (SNPs) especially in noncoding regions, apparent mutational hotspots and areas of
      low K values by recombination should be noted since the unequal distribution of
      SNPs will reduce the power of SNPs as genetic maker. Combining the complete
      sequences' data of both RH genes with serological findings will provide
      beneficial information with which to elucidate the mechanism of recombination,
      mutation, polymorphism, and evolution of other genes containing the RH gene as
      well as to analyze Rh variants and develop new methods of Rh genotyping.

PMID- 10924336
TI  - Cyclic expression of class I alcohol dehydrogenase in male rats treated with
      ethanol.
AB  - Continuous infusion of ethanol-containing diets has been demonstrated to generate
      well-defined pulses in blood and urine ethanol concentrations that occur with a
      frequency of approximately 6 days. The present study aimed to determine if
      hepatic class I alcohol dehydrogenase was the cause of these cycles. Adult male
      rats were fed an ethanol-containing diet by continuous intragastric infusion.
      Hepatic ADH activity, class I ADH mRNA level and rate of class I ADH gene
      transcription fluctuated in a cyclic pattern that positively correlated with
      UECs, and inhibition of ADH with 4-methylpyrazole abolished the UEC pulses. These
      data demonstrate for the first time an ethanol-dependent regulation of rat
      hepatic class I ADH. The cyclic behavior of the ethanol levels correlates with
      changes in class I ADH expression and implies adaptability of the ethanol
      eliminating system to high concentrations of alcohol.

PMID- 10924337
TI  - Keratinocyte-derived chemotactic cytokines: expressional modulation by nitric
      oxide in vitro and during cutaneous wound repair in vivo.
AB  - Inhibition of inducible nitric oxide-synthase (iNOS) enzymatic activity during
      cutaneous wound repair leads to severely impaired tissue regeneration. To assess
      whether disturbed leukocyte infiltration might participate in impaired repair, we
      determined expressional kinetics of neutrophil-attracting macrophage inflammatory
      protein-2 (MIP-2), and monocyte-attracting macrophage chemoattractant protein-1
      (MCP-1) using an excisional wound healing model in mice. MCP-1 was induced in
      epithelial keratinocytes upon wounding, and our data indicate that NO serves a
      negative regulatory role for MCP-1 expression in vivo, as clearly reduced numbers
      of wound margin keratinocytes associated with NO-deficient repair compensate for
      high MCP-1 expression levels observed during normal healing. MIP-2 expression was
      restricted to hair follicles which were not reduced in number during NO-deficient
      repair. In vitro studies confirmed a regulatory role of NO for keratinocyte
      derived chemokine expression, as NO attenuated IL-1beta- and TNF-alpha-induced
      MCP-1 mRNA expression, whereas NO augmented IL-1beta-induced IL-8 (functional
      human homolog to murine MIP-2) mRNA expression in the human keratinocyte cell
      line HaCaT.

PMID- 10924338
TI  - Difference in effective dosage of genistein on bone and uterus in ovariectomized
      mice.
AB  - Phytoestrogen including soybean isoflavones has structural similarity to estrogen
      and exhibits beneficial effects on bone tissue to protect against bone loss under
      estrogen-deficient conditions. Recent studies also indicate a possible action of
      isoflavones as endocrine disrupters in reproductive tissues. In this study, we
      administered various dosages of genistein to ovariectomized (OVX) mice, and
      compared the effective dosages of genistein on bone and uterus. Treatment with
      genistein at 0.7 mg/day prevented trabecular bone loss in OVX mice without
      hypertrophic effects on the uterus, while administration of 5 mg/day of genistein
      induced uterine hypertrophy. The serum levels of genistein in OVX mice treated
      with 0.7 mg/day and 5 mg/day were 3-fold (1.3 nmol/ml) and 50-fold (20.4 nmol/ml)
      higher than that in OVX mice. These results suggest that there is a marked
      difference between genistein dosages that protect against bone loss and those
      that induce uterine hypertrophy.

PMID- 10924339
TI  - Cardiac amyloid in patients with familial amyloid polyneuropathy consists of
      abundant wild-type transthyretin.
AB  - Patients with familial amyloid polyneuropathy (FAP) are now cured by liver
      transplantation, but cardiac amyloidosis would further progress even after liver
      transplantation in some patients. To clarify the pathological mechanism of the
      progress of cardiac amyloidosis in FAP, we investigated cardiac tissues obtained
      from 6 FAP patients with 3 different types of TTR mutations. One of them had
      undergone liver transplantation and one year later died of cardiac amyloidosis.
      We determined clinical severity of cardiac involvement of those patients and
      characterized amyloid fibril proteins depositing in their cardiac muscles by
      immunohistochemistry, mass spectrometry and isoelectric focusing. All the
      patients had cardiac dysfunction and increased cardiac weight. Diffuse deposition
      of TTR-related amyloid was seen in their myocardium on microscopic examination.
      Amyloid fibrils of the heart were composed of wild-type TTR as well as variant
      TTR at a ratio of about 1:1 in 5 patients without liver transplantation. In the
      patient with a transplanted liver, about 80% of the cardiac amyloid consisted of
      wild-type TTR. Wild-type TTR contributes greatly to the development of amyloid
      deposition in the heart of FAP patients regardless of the types of TTR mutations.

PMID- 10924340
TI  - Interleukin-6 negatively regulates the expression of pregnane X receptor and
      constitutively activated receptor in primary human hepatocytes.
AB  - The marked impairment of hepatic drug metabolism during inflammation and
      infections has been known for many years and shown to result from down-regulation
      of cytochrome P450s (CYP) by cytokines. However, the mechanism of this repression
      is unknown. Using primary cultures of human hepatocytes, we show here that
      interleukin-6 (IL-6) rapidly and markedly decreases the expression of PXR
      (pregnane X receptor) and CAR (constitutively activated receptor) mRNAs, but does
      not affect the levels of dioxin receptor and glucocorticoid receptor mRNA. In
      parallel, IL-6 decreases both rifampicin- and phenobarbital-mediated induction of
      CYP2B6, CYP2C8, CYP2C9, and CYP3A4. As the transcriptional activity of PXR and
      CAR is not affected by IL-6 in cell-based reporter assays, our data suggest that
      the loss of CYP2 and CYP3 inducibility results from the negative regulation of
      PXR and CAR gene expression by this cytokine.

PMID- 10924341
TI  - Antibacterial and hemolytic activities of single tryptophan analogs of
      indolicidin.
AB  - The structure and biological activities of analogs of the bovine neutrophil
      antibacterial and hemolytic peptide indolicidin, ILPWKWPWWPWRR-amide, where one
      tryptophan at 4th, 8th, or 11th position has been retained and the others
      replaced by leucine, have been investigated. All the single tryptophan analogs
      exhibit antibacterial activity. However, unlike indolicidin, they do not lyse
      erythrocytes. Structure analysis by circular dichroism spectroscopy indicates
      that the analogs are unordered in aqueous medium and adopt beta-turn structures
      in trifluoroethanol and micelles. The tryptophan residues in indolicidin appear
      to be essential for hemolytic activity but not antibacterial activity. The
      nonspecific biological activities of indolicidin and specific antibacterial
      activity of single tryptophan analogs suggest that in short peptides, a motif
      composed of hydrophobic amino acids with the exception of tryptophan, interspaced
      with proline residues and cationic amino acids at the N or C termini would favor
      selective antibacterial activity.

PMID- 10924342
TI  - Effect of cholera toxin on rat liver lysosome acidification.
AB  - We have shown that cholera toxin and cAMP greatly increase both acidification
      rates of liver endosomes and the liver and endosome content of fluid-phase
      endocytosis probes. In this study lysosomes were purified from control and
      cholera toxin-treated livers that were pulsed with fluorescein conjugated dextran
      and chased overnight. Cholera toxin-treated livers weighed less, contained less
      protein and exhibited higher contents of lysosomal marker enzymes, consistent
      with the catabolic effects of this agent. By contrast to its effects on
      endosomes, cholera toxin had no consistent or significant effect on lysosome
      acidification rates, steady-state internal pH or potassium content, proton leak
      rates or fluorescein-dextran content. We conclude that cholera toxin and cAMP
      predominantly alter earlier steps of endocytosis but may also increase transfer
      of probes from lysosomes to bile.

PMID- 10924343
TI  - De novo methylation at intronic CpG islands of Igf2r is associated with decreased
      expression of antisense RNA in aged mice.
AB  - Changes in cytosine methylation status of several genes have been implicated in
      the aging process. We have examined methylation status of differentially
      methylated regions of insulin-like growth factor II receptor gene during mouse
      senescence. Bisulfite-aided genomic sequencing revealed that methylated CpG
      residues were extended beyond the 3' boundary of de novo methylation sequence of
      DMR2 in aged mice. Furthermore, the de novo methylation of DMR2 in aged mice was
      associated with decreased expression of antisense transcript which recruits DMR2
      as a promoter. On the contrary, methylation status of DMR1 was well-maintained
      during senescence. Accordingly, no significant changes in expression levels of
      sense transcripts were observed during the course of mouse aging.

PMID- 10924344
TI  - A thermophilic apoglucose dehydrogenase as nonconsuming glucose sensor.
AB  - Blood glucose is a clinically important analytes for diabetic health care. In
      this preliminary report we describe a protein biosensor for d-glucose based on a
      thermostable glucose dehydrogenase. The glucose dehydrogenase was noncovalently
      labeled with 8-anilino-1-naphthalene sulfonic acid (ANS). The ANS-labeled enzyme
      displayed an approximate 25% decrease in emission intensity upon binding glucose.
      This decrease can be used to measure the glucose concentration. Our results
      suggest that enzymes which use glucose as their substrate can be used as
      reversible and nonconsuming glucose sensors in the absence of required cofactors.
      Moreover, the possibility of using inactive apoenzymes for a reversible sensor
      greatly expands the range of proteins which can be used as sensors, not only for
      glucose, but for a wide variety of biochemically relevant analytes.

PMID- 10924346
TI  - Hypotonic stress-induced NO production in endothelium depends on endogenous ATP.
AB  - The mechanism by which mechanical stress induces nitric oxide (NO) synthesis in
      endothelium is still controversial. Hypotonic stress (HTS, -20%) induced ATP
      release, which evoked Ca(2+) transients in bovine aortic endothelial cells
      (BAEC). HTS also induced NO synthesis, assessed by DAF-2 fluorescence, which was
      suppressed by inhibiting endogenous ATP-induced Ca(2+) transients with suramin or
      neomycin. Exogenously applied ATP mimicked these responses. Pretreatment with
      wortmannin did not affect DAF-2 fluorescence, suggesting that Akt phosphorylation
      was not involved in HTS-induced NO synthesis. These results indicate that
      endogenous ATP plays a central role in HTS-induced NO synthesis in BAEC.

PMID- 10924345
TI  - Inhibition of serine amidohydrolases by complexes of vanadate with hydroxamic
      acids.
AB  - Serine beta-lactamases are inhibited by phosphonate monoester monoanions. These
      compounds phosphonylate the active site serine hydroxyl group to form inert,
      covalent complexes. Since spontaneous hydrolysis of these phosphonates is
      generally quite slow, the beta-lactamase active site must have considerable
      affinity for the (presumably) pentacoordinated phosphonyl transfer transition
      state. Structural analogs of such a transition state might well therefore be
      effective and novel beta-lactamase inhibitors. Complexes of vanadate with
      hydroxamic acids may be able to achieve such a structure. Indeed, mixtures of
      these two components, but neither one alone, were found to inhibit a typical
      class C beta-lactamase. A Job plot of the inhibition by vanadate/benzohydroxamic
      acid mixtures indicated that the inhibitor was a 1:1 complex for which an
      inhibition constant of 4.2 microM could be calculated. A bacterial DD-peptidase,
      structurally similar to the beta-lactamase, was also inhibited (K(i) = 22 microM)
      by this complex. A similar rationale would suggest that other serine hydrolases
      might also be inhibited by these mixtures. In fact, chymotrypsin was inhibited by
      a complex of vanadate with benzohydroxamic acid (K(i) = 10 microM) and elastase
      by a complex with acetohydroxamic acid (K(i) = 90 microM).

PMID- 10924347
TI  - Regulation by adrenocorticotropic hormone and arachidonate of the expression of
      acyl-CoA synthetase 4, an arachidonate-preferring enzyme expressed in
      steroidogenic tissues.
AB  - Acyl-CoA synthetase 4 (ACS4) is an arachidonate-preferring enzyme abundant in
      steroidogenic tissues. We demonstrate that ACS4 expression in steroidogenic
      tissues in vivo is induced by adrenocorticotropic hormone (ACTH) and suppressed
      by glucocorticoid. ACTH also induced ACS4 protein but not its mRNA in Y1
      adrenocortical tumor cells, whereas both ACS4 mRNA and protein were increased by
      dibutyryl cAMP (db-cAMP) and forskolin. Furthermore, the levels of ACS4 mRNA and
      protein in Y1 cells were induced by arachidonate. These data suggest that ACS4
      expression in steroidogenic cells is regulated in coordination with induced
      steroidogenesis and arachidonate released by cholesterol ester hydrolase.

PMID- 10924348
TI  - Hepatic metabolism of ergot alkaloids in beef cattle by cytochrome P450.
AB  - This study was conducted to investigate the involvement of cytochrome P450 3A
      (CYP3A) in the metabolism of ergotamine in beef liver microsomes. When incubated
      with liver microsomes, ergotamine was hydroxylated to metabolites M1 and M2.
      Similarly, its isomer was hydroxylated to M1-Iso and M2-Iso (8-hydroxy
      derivatives). Further incubation resulted in a second hydroxylation of M1 and M2
      to metabolites M3 and M4 (8,9-dihydroxy derivatives). Maximum formation of
      metabolites was reached after 20 min, and ergotamine and its isomer were almost
      totally metabolized after 60 min of incubation. The formation of these
      metabolites was completely dependent on the presence of NADPH or the NADPH
      generating system and was also dependent on microsome concentration. Ergotamine
      was converted at a rate of 2 nM/microgram microsome/min when incubated with
      bovine liver microsomes to produce a metabolite profile (M1, M2, M1-Iso and M2
      Iso) similar to the metabolites produced (2.2 nM/microgram/min) when ergotamine
      was incubated with liver microsomes of dexamethasone treated rats. This work
      provides information on the modification of ergotamine in bovine liver microsomes
      by CYP3A, which is of importance in understanding the detoxification and the
      clearance of ergotamine and other ergot alkaloids by bovine.

PMID- 10924349
TI  - A possible role of the Na(+)/K(+)-ATPase for O(2) production from H(2)O(2).
AB  - We are attempting to supply a new insight on interaction between Na(+)/K(+)
      ATPase and H(2)O(2). We demonstrate that in vitro the Na(+)/K(+)-ATPase, a non
      heme-protein, is able to disproportionate H(2)O(2) catalatically into dioxygen
      and water, as well as C(40) catalase. By polarography, we quantify O(2)
      production and by Raman spectroscopy H(2)O(2) consumption. A comparative analysis
      of kinetics parameters relative to O(2) production shows that for Na(+)/K(+)
      ATPase the affinity of the catalytic site able to transform H(2)O(2) into O(2) is
      twice weaker than that for C(40) catalase. It also shows that the molar activity
      for O(2) production is 300-fold weaker for ATPase than for catalase. Inhibitors,
      pH and GSH studies highlight the differences between the heme- and nonheme
      proteins. Indeed, for C(40), NaN(3) is strongly inhibiting, but much less for
      ATPase. The pH range for the catalatic activity of ATPase is wide (6.5 to 8.5),
      while it is not for C(40) catalase (optimum at pH 8). The Na(+)/K(+)-ATPase
      catalatic activity is reduced in presence of glutathione, while it is not the
      case with C(40) catalase.

PMID- 10924350
TI  - Bovine lactoperoxidase and its recombinant: comparison of structure and some
      biochemical properties.
AB  - Biochemical properties of bovine lactoperoxidase isolated from milk and
      recombinant bovine lactoperoxidase expressed by Chinese hamster ovary cells were
      compared. The natural and recombinant lactoperoxidases showed the same
      conformational features as determined by circular dichroism (CD) measurements.
      The alpha-helix, beta-structure, and unordered structure contents were found to
      be 17. 8, 54.2, and 28.0% for the natural lactoperoxidase and 18.6, 50.1, and
      31.3% for the recombinant lactoperoxidase, respectively. The microenvironments of
      aromatic amino acid residues in both lactoperoxidases seemed to be the same,
      although the CD spectral band due to the Soret band differed slightly. A
      difference in the pH-dependent spectral changes of absorbance at 413 nm was
      observed. From a pepsin hydrolysate of lactoperoxidase, a heme-binding peptide
      was isolated by reverse-phase HPLC and its amino acid sequence was examined.

PMID- 10924351
TI  - Sequence of genome segments 1, 2, and 3 of the grass carp reovirus (Genus
      Aquareovirus, family Reoviridae).
AB  - The genome segments 1, 2, and 3 of the grass carp reovirus (GCRV), a tentative
      species assigned to genus Aquareovirus, family Reoviridae, were sequenced. The
      respective segments 1, 2, and 3 were 3949, 3877, and 3702 nucleotides long.
      Conserved motifs 5' (GUUAUUU) and 3' (UUCAUC) were found at the ends of each
      segment. Each segment contains a single ORF and the negative strand does not
      permit identification of consistent ORFs. Sequence analysis revealed that VP2 is
      the viral polymerase, while VP1 might represent the viral guanylyl/methyl
      transferase (involved in the capping process of RNA transcripts) and VP3 the
      NTPase/helicase (involved in the transcription and capping of viral RNAs). The
      highest amino acid identities (26-41%) were found with orthoreovirus proteins.
      Further genomic characterization should provide insight about the genetic
      relationships between GCRV, aquareoviruses, and orthoreoviruses. It should also
      permit to precise the taxonomic status of these different viruses.

PMID- 10924352
TI  - Adenoviral vector cytotoxicity depends in part on the transgene encoded.
AB  - First-generation adenoviral vectors induce G(2)/M arrest and cell death at high
      multiplicities of infection (m.o.i.'s) in vitro. It is unclear whether this
      cytotoxicity is entirely adenoviral gene related or influenced in part by the
      encoded transgene. We examined this question in epithelial cells using seven
      vectors at relatively low (50) or higher (200) m.o.i.'s. The vectors contained no
      transgene (+/-promoter), transgenes encoding a cytoplasmic reporter protein (two
      luciferase constructs; beta-galactosidase), or transgenes encoding a secretory
      protein (alpha1-antitrypsin; growth hormone). After 24 h with a m.o.i. of 50,
      vectors encoding cytoplasmic reporter proteins led to greatest cytotoxicity
      (approximately 35-40% cells in G(2)/M). Vectors without a transgene resulted in
      lower cytotoxicity (approximately 15%, minus, or 23%, plus promoter, cells in
      G(2)/M). Vectors encoding secretory proteins led to approximately 22-25% cells in
      G(2)/M. A similar pattern resulted when cell number was measured. Results were
      unrelated to the steady-state levels of transgene product. At the higher m.o.i.,
      all vectors caused substantial growth retardation. This is the first
      demonstration that adenoviral vector-induced cytotoxic effects are in part
      related to the transgene encoded.

PMID- 10924353
TI  - Hepatocyte growth factor decreases sensitivity to chemotherapeutic agents and
      stimulates cell adhesion, invasion, and migration.
AB  - Hepatocyte growth factor (HGF), also known as scatter factor (SF), plays an
      important role in cell:cell adhesion, cell proliferation, motility, and
      invasiveness of epithelial cells and tumor cells. In this study, we examined the
      effects of HGF on these types of biological activities and chemosensitivity in
      Chinese hamster ovary (CHO) cells by stable transfection of the HGF gene. HGF
      transfected clones produced very high titers of HGF protein, whereas control
      vector-transfected clones did not produce detectable HGF protein. HGF-transfected
      clones showed modestly increased proliferation rates and became more resistant to
      cell death and apoptosis caused by two anticancer drugs, adriamycin (ADR) and
      camptothecin (CPT), compared to controlvector-transfected clones. Furthermore,
      HGF-transfected clones also exhibited increased activities of cell adhesion,
      migration, and invasion. The current study is the first demonstration that
      overexpression of the HGF gene affects chemosensitivity and cell metastasis
      behaviors, suggesting that HGF signaling pathway is a promising new target of
      therapeutic intervention of tumors.

PMID- 10924355
TI  - Pyruvate cycling and implications for regulation of gluconeogenesis in the
      insect, Manduca sexta L.
AB  - Pyruvate cycling was examined in the insect Manduca sexta L. (2-(13)C)pyruvate
      was injected into 5th instar larvae maintained on a semisynthetic high sucrose,
      low sucrose, or sucrose-free diet. Pyruvate cycling and gluconeogenesis were
      determined from the distribution of (13)C in blood metabolites, including
      trehalose, the blood sugar of insects, and alanine. Pyruvate cycling was evident
      from the (13)C enrichment of alanine C3, synthesized by transamination of
      pyruvate following carboxylation to oxaloacetate and cycling through
      phosphoenolpyruvate. Based on the relative (13)C enrichments of alanine C2 and
      C3, insects maintained on the high sucrose diet displayed higher levels of
      cycling than insects on the other diets. Insects on all the diets, when
      subsequently starved, displayed low levels of cycling. Gluconeogenesis was
      evident in insects on sucrose-free or low sucrose diets from the selective (13)C
      enrichment in trehalose. The level of gluconeogenesis relative to glycolysis was
      indicated by the (13)C enrichment of trehalose C6 and alanine C3, both
      enrichments metabolically derived in the same manner. Insects starved after
      maintenance on the sucrose-free or low sucrose diets remained glucogenic. Insects
      on the high sucrose diet were not glucogenic, and subsequent starvation did not
      induce gluconeogenesis. The results indicate that pyruvate kinase plays a
      critical role in regulating the gluconeogenic/glycolytic balance, and that
      inhibition of pyruvate kinase is a principal regulatory event during induction of
      de novo trehalose synthesis. Gluconeogenesis failed to maintain homeostatic
      levels of blood trehalose, supporting the conclusion that blood sugar level may
      be important for mediating nutrient intake. Possible factors involved in the
      regulation of gluconeogenesis in insects are discussed.

PMID- 10924354
TI  - New thiol and sulfodiimine metalloproteinase inhibitors and their effect on human
      microvascular endothelial cell growth.
AB  - Matrix metalloproteinases (MMPs, matrixins) are a family of homologous zinc
      endopeptidases that may play a very important role in many physiological and
      pathological processes, e.g., the initiation of angiogenesis. Two new matrixin
      inhibitors were synthesized and characterized. A thiol inhibitor MAG-283 had
      IC(50) values of 480, 3, 280, 14, 1.1, and 2.3 nM against human interstitial
      collagenase (MMP-1), gelatinase A (MMP-2), stromelysin (MMP-3), matrilysin (MMP
      7), neutrophil collagenase (MMP-8), and gelatinase B (MMP-9), respectively. A
      sulfodiimine inhibitor YLL-224 had IC(50) values of 180, 63, 4500, 210, 5.9, and
      44 nM against MMP-1, -2, -3, -7, -8, and -9, respectively. Human skin
      microvascular endothelial cells were treated with these two compounds in culture.
      These inhibitors at very low micromolar concentrations suppressed proliferation
      of the endothelial cells stimulated by acidic fibroblast growth factor and
      vascular endothelial growth factor. They also partially blocked cell invasion
      through type IV collagen. These results suggested a correlation between the anti
      metalloenzyme activity and the effects of these inhibitors on the growth and
      invasion of endothelial cells.

PMID- 10924356
TI  - ABC1 gene expression and ApoA-I-mediated cholesterol efflux are regulated by LXR.
AB  - ATP-binding cassette transporter 1 (ABC1) mediates the active efflux of
      cholesterol from cells to apolipoproteins. To study the mechanisms of regulation
      of ABC1 gene expression, RAW 264.7 macrophages were transiently transfected with
      ABC1 promoter-luciferase reporter gene-fusion constructs. Transcription from a
      1.64 kb fragment was induced by cholesterol loading but was not responsive to
      cAMP. Treatment of the cells with 9-cis retinoic acid or 20(S)
      hydroxycholesterol, ligands for the nuclear receptors LXR and RXR, resulted in a
      marked induction of luciferase expression. The responsible control element was
      mapped to an imperfect direct repeat of the nuclear receptor half-site TGACCT
      separated by four bases (DR-4) that binds LXR/RXR heterodimers. Endogenous ABC1
      gene expression in RAW cells and apolipoprotein A-I mediated cholesterol efflux
      were also upregulated by both receptor ligands. These findings raise the
      possibility that ligands that activate the LXR-RXR heterodimer may be useful for
      the therapeutic modulation of the ABC1 pathway.

PMID- 10924357
TI  - Tetracycline-inducible CaM kinase II silences hypertrophy-sensitive gene
      expression in rat neonate cardiomyocytes.
AB  - Recent work from this laboratory both in rat primary cardiomyocytes and in
      ventricular tissue of transgenic mouse models of induced hypertrophy has
      identified two Ca(2+)/calmodulin-dependent nuclear signaling cascades. The first
      involves the phosphatase calcineurin (CaN). The second is the CaM kinase kinase
      cascade which involves CaM kinase I and CaM kinase IV. Each of these signaling
      cascades strongly up-regulate transcription of hypertrophy-sensitive genes in the
      rat ventricular cardiomyocyte. We have documented that over-expression of an
      active form of CaM kinase II silenced transcriptional induction of hypertrophy
      sensitive genes. The purpose of this study was to generate an inducible CaM
      kinase II expression system and correlate its expression with the silencing of
      hypertrophic-sensitive reporters. A truncated form of CaM KII, CaM KII (1-290)
      was subcloned downstream and proximal to a promoter under transcriptional control
      (induction) of the tetracycline-regulated transcription factor, tet
      TransActivator (tTA). Hypertrophy-sensitive reporter activity in primary
      cardiomyocytes was silenced when tet-inducible CaM KII was co-expressed with
      plasmids harboring active forms of CaN, CaM KI or CaM KIV. For instance, induced
      CaM KII expression silenced CaN, CaM kinase I, or CaM kinase IV driven ANF
      reporter activity 4.9-, 2.9-, and 6.9-fold below their maximal values,
      respectively. Myocyte exposure to doxycycline (DOX) blocked tTA-driven CaM KII
      expression and restored CaN/CaM KI or CaN/CaM KIV driven reporter activation.
      This study demonstrates, for the first time, that active CaM KII silences Ca(2+)
      sensitive nuclear signaling cascades for transcriptional up-regulation of
      cardiomyocyte hypertrophy.

PMID- 10924358
TI  - Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a
      leucine-zipper and a sterile-alpha motif.
AB  - A novel mixed lineage kinase-like protein ZAK, containing a leucine-zipper (LZ)
      and a sterile-alpha motif (SAM), was cloned. This cDNA has 2456 bp and encodes a
      protein of 800 amino acids that contains a kinase catalytic domain, a leucine
      zipper and a SAM. The molecular weight of this protein is 91kDa. Northern blot
      analysis revealed that the expression of this ZAK gene is found in various parts
      of human tissues. We also found that ZAK proteins might form homodimers or
      oligomers in mammalian cells. MLKs have been proposed to function as mitogen
      activated protein kinase kinase kinase in pathways leading to MAPK cascade. The
      expression of ZAK in mammalian cells specifically leads to the activation of the
      JNK/SAPK pathway as well as the activation of transcription factor, NF-kappaB.
      Overexpression of the ZAK gene induces the apoptosis of a hepatoma cell line.

PMID- 10924359
TI  - Study on colloidal Au-enhanced DNA sensing by quartz crystal microbalance.
AB  - Colloidal Au is reported for enhancement the immobilization capacity and
      ultimately detection limit of DNA using quartz crystal microbalance (QCM).
      Immobilization of approximately 12 nm-diameter colloidal Au on to an Au-coated
      QCM resulted in an easier attachment of oligonucleotide, with a mercaptohexyl
      group at the 5'-phosphate end and an increased capacity for nucleic acid
      detection. DNA immobilization and hybridization was monitored from QCM frequency
      changes. Hybridization was induced by exposure of the DNA-containing films to
      complementary DNA in solution. A much higher sensitivity was obtained for the
      analyte. The Au nanoparticle films on the Au plate provide a novel means for the
      fabrication of DNA sensor.

PMID- 10924360
TI  - The use of the novel substrate-heme complex approach in the derivation of a
      representation of the active site of the enzyme cholesterol side chain cleavage.
AB  - The previously reported substrate-heme complex approach is used to study the
      binding of type II inhibitors of the enzyme cholesterol side chain cleavage
      (CSCC), a cytochrome P-450 dependent enzyme involved in the oxidative cleaveage
      of the C(20)-C(22) bond of cholesterol. Using the derived model, we have
      rationalised the inhibitory activity of a number of compounds including
      aminoglutethimide and pyridoglutethimide and the enantiomers of ketoconazole.

PMID- 10924361
TI  - Phosphorylation of CPI-17, an inhibitor of myosin phosphatase, by protein kinase
      N.
AB  - CPI-17 is a phosphorylation-dependent inhibitory protein for smooth muscle myosin
      phosphate. Phosphorylation at Thr(38), in vitro, by protein kinase C or Rho
      kinase enhances the inhibitory potency toward myosin phosphatase. Phosphorylation
      of CPI-17 by protein kinase N (PKN), a fatty acid- and Rho-activated
      serine/threonine kinase, and its effect on smooth muscle myosin phosphatase
      activity were investigated. CPI-17 was phosphorylated by GST-PKN-CAT, a
      constitutively active GST-fusion fragment of PKN, to 1.46 mol of P/mol of CPI-17,
      in vitro. The K(m) value of CPI-17 for PKN was 0.96 microM. Phosphorylation of
      PKN dramatically increased the inhibitory effect of CPI-17 on myosin phosphatase
      activity. The major and inhibitory phosphorylation site was identified as Thr(38)
      using a point mutant of CPI-17 and a phosphorylation-state specific antibody.
      Thus, CPI-17 is a substrate of PKN and might be involved in the Ca(2+)
      sensitization of smooth muscle contraction as a downstream effector of Rho and/or
      arachidonic acid.

PMID- 10924362
TI  - Small peptides Do not inhibit human non-pancreatic secretory phospholipase-A(2)
      (Type IIA).
AB  - Seven small peptides, that are among the most potent reported inhibitors of
      secreted mammalian phospholipases A(2), were found not to inhibit processing of a
      small phospholipid substrate by human non-pancreatic secretory phospholipase A(2)
      (type IIa), under conditions where certain non-peptides are potent inhibitors at
      nanomolar concentrations.

PMID- 10924363
TI  - Opposing actions of cGMP and calcium on the conductance of the F(0) subunit c
      pore.
AB  - Subunit c of ATP synthase can be purified from neuronal plasma membrane and from
      the inner mitochondrial membrane. In the latter location the hydrophobic 75 amino
      acid protein is one component of the F(1) F(0) ATP synthase complex but in the
      former it is alone as a pore that is capable of generating spontaneous electrical
      oscillations. Pure mammalian subunit c when reconstituted in lipid bilayers and
      voltage clamped, yields a voltage sensitive pore that conducts a cation current
      regulated by calcium. The current is here found to be activated by cGMP with a
      K(M) ranging from 14 nM to 19 microM depending on calcium and temperature. It is
      sensitively inhibited by a number of ligands. The K(I) for calcium ranges from
      100 nM to 100 microM depending on cGMP and temperature. DCCD inhibits with a
      K(app) of 100 nM. The polyamine nicotine inhibits at 84 nM. The pore has
      properties that would allow it to deliver sodium or calcium through the cell
      membrane in a controlled manner while maintaining membrane polarization.

PMID- 10924364
TI  - Mutations on the hinge region of leukocyte elastase inhibitor determine the loss
      of inhibitory function.
AB  - Leukocyte elastase inhibitor (LEI) is a cytosolic component of lung macrophages
      and blood leukocytes that inhibits neutrophil elastase. LEI is a member of the
      serpin superfamily, these proteins, mostly protease inhibitors, are thought to
      undergo a conformational change upon complex formation with proteinase that
      involves partial insertion of the hinge region of the reactive centre loop into a
      beta-sheet of the inhibitor. In this work three mutations were produced in the
      hinge region of elastase inhibitor that abolish the inhibition activity of LEI
      and transform the protein in a substrate of the elastase. This result
      demonstrates that the inhibitory mechanism of serpin is common to LEI.

PMID- 10924365
TI  - Insulin activation of mitogen-activated protein (MAP) kinase and Akt is
      phosphatidylinositol 3-kinase-dependent in rat adipocytes.
AB  - To explore the mechanism of MAP kinase activation in adipocytes, we examined the
      possible involvement of several candidate signaling proteins. MAP kinase activity
      was markedly increased 2-4 min after treatment with insulin and declined to basal
      levels after 20 min. The insulin-dependent tyrosine phosphorylation of IRS-1 in
      the internal membrane and its association with phosphatidylinositol 3 (PI3)
      kinase preceded MAP kinase activation. There was little or no tyrosine
      phosphorylation of Shc or association of Grb2 with Shc or IRS-1. Specific PI3
      kinase inhibitors blocked the insulin-mediated activation of MAP kinase. They
      also decreased the activation of MAP kinase by PMA and EGF but to a much lesser
      extent. Insulin induced phosphorylation of AKT on serine/threonine residues, and
      its effect could be blocked by PI3 kinase inhibitors. These results suggest that
      the insulin-dependent activation of MAP kinase in adipocytes is mediated by the
      IRS-1/PI3 kinase pathway but not by the Shc/Grb2/SOS pathway.

PMID- 10924366
TI  - Expression cloning of KCRF, a potassium channel regulatory factor.
AB  - By functional coexpression screening of a rat cDNA library in Xenopus oocytes, we
      have cloned a protein (KCRF: K Channel Regulatory Factor) that reduces currents
      of several K(+) channels: G protein-activated GIRK1/4 (K(ir)3.1/K(ir)3.4), inward
      rectifier IRK1 (K(ir)2.1), and voltage-dependent K(V)1.1/K(V)beta1.1. KCRF did
      not modulate two other K(+) channels: ROMK1 (K(ir)1.1) and GIRK1/2
      (K(ir)3.1/K(ir)3.2) and the voltage-dependent L-type Ca(2+) channels. Western
      blot analysis showed that KCRF is ubiquitous in rat tissues. Biochemical and
      electrophysiological experiments revealed that coexpression of KCRF causes a
      decrease in the level of expression of IRK1 and K(V)1.1/K(V)beta1.1 proteins in
      the oocytes.

PMID- 10924367
TI  - Search for UV-responsive genes in human cells by differential mRNA display:
      involvement of human ras-related GTP-binding protein, Rheb, in UV susceptibility.
AB  - The search for genes responsible for the sensitivity of human cells to cell
      killing effects of UV is an important area of biological research. To identify
      candidate genes responsible for UV sensitization, levels of mRNA expression were
      compared between UV-sensitive RSa cells and UV-resistant variant UV(r)-1 cells,
      using a differential display method and Northern blot analysis. Messenger RNA
      expression levels of human Ras homologue enriched in brain (Rheb) and/or a Rheb
      like gene were up-regulated and slightly decreased in UV-irradiated RSa and UV(r)
      1 cells, compared to in mock-irradiated cells, respectively. RSa and UV(r)-1
      cells, both of which were treated with antisense oligonucleotides for Rheb RNA,
      exhibited an increased resistance to UV cell-killing. It remains unclear why
      UV(r)-1 cells are resistant to UV yet express Rheb mRNA at high levels. However,
      the results of antisense experiments together with the up-regulation in UV
      irradiated RSa cells, suggest that Rheb is involved in the UV sensitization of
      both cells to UV cell-killing.

PMID- 10924368
TI  - S100A1, a new marker for acute myocardial ischemia.
AB  - The Ca(2+)-binding S100A1 protein displays a specific and differential expression
      in the human myocardium and is considered to be an important regulator of heart
      function. Because of its high expression levels in the heart we tested the
      performance of S100A1 as a diagnostic indicator of acute myocardial damage.
      Therefore, we established a S100A1-specific sandwich ELISA and determined the
      S100A1 plasma levels in patients with signs of acute myocardial ischemia. The
      concentration-time course of S100A1 was distinct from that of the "classical"
      biochemical markers, CK, CKMB, and troponin I, showing an early rise and a fast
      decline in plasma after the ischemic event. We suggest that S100A1 should be
      included in combinatorial measurements as an early diagnostic marker for ischemic
      coronary diseases.

PMID- 10924370
TI  - Knotting of distal ventriculoperitoneal shunt tubing

PMID- 10924369
TI  - Cloning of DPK, a novel dendritic cell-derived protein kinase activating the
      ERK1/ERK2 and JNK/SAPK pathways.
AB  - Mitogen-activated protein kinase (MAPK) cascades are the major signaling systems
      transducing extracellular signals into intracellular responses, which mainly
      include the extracellular signal-regulated kinase (ERK) pathway, the c-Jun N
      terminal kinase/stress-activated protein kinase (JNK/SAPK) pathway, and the p38
      pathway. From dendritic cell cDNA library, we isolated a full-length cDNA
      encoding a potentially novel 898-residue kinase, which was designated DPK. The
      protein contained a potential kinase domain at the N-terminal exhibiting homology
      with MEKK1-, MEKK2-, MEKK3-, MEKK4-, MEKK5-, Tpl-2-, and p21-activated kinases
      (PAKs), but no GTPase-binding domain which is characteristic of PAKs. Northern
      blotting analysis showed that DPK was ubiquitously expressed in normal tissues,
      with abundant expression in kidney, skeletal muscle, heart, and liver. When
      overexpressed in transfected NIH3T3 cells, it could activate both the ERK1/ERK2
      pathway and the SAPK pathway in a dose-dependent manner, but not affect the p38
      pathway. These findings suggested that DPK might be a novel candidate MAPKKK.

PMID- 10924371
TI  - The MRI appearances of anterior opercular syndrome in a child with recurrent
      herpes simplex encephalitis.

PMID- 10924372
TI  - Ultrasound appearances of testicular epidermoid cysts.
AB  - Benign testicular tumours are uncommon but if recognized can enable a
      conservative approach to surgery to be recommended. This pictorial review
      demonstrates the variety of sonographic appearances of testicular epidermoid
      cysts correlating them with pathological findings in 19 lesions, the largest
      reported imaged series to date. Atchley, J. T. M., Dewbury, K. C. (2000).
      Clinical Radiology 55, 493-502.

PMID- 10924373
TI  - Diagnostic imaging of choroid plexus disease.
AB  - Disorders of the choroid plexus, a central nervous system structure, are rare,
      but can pose diagnostic difficulties. The purpose of this review is to illustrate
      the computed tomography and magnetic resonance imaging findings of a wide
      spectrum of lesions that affect the choroid plexus. The areas covered include (1)
      neoplasms (papilloma, leukaemia, meningioma, lymphoma and metastases); (2)
      infections (bacterial, fungal and viral); (3) cysts; (4) haemorrhage; (5)
      congenital abnormalities (Sturge-Weber syndrome, Klippel-Trenaunay-Weber syndrome
      and vascular malformations); and (6) non-infectious inflammatory disorders
      (xanthogranulomas, inflammatory pseudotumour, neurosarcoidosis, rheumatoid nodule
      and villous hypertrophy). Few of the patterns of choroid plexus involvement are
      specific for a particular pathological process. Guermazi, A. (2000) Clinical
      Radiology 55, 503-516.

PMID- 10924374
TI  - The role of hepatic arterial Doppler ultrasound after liver transplantation: an
      'audit cycle' evaluation.
AB  - AIMS: To compare the diagnostic performance of hepatic arterial (HA) Doppler
      ultrasound post-liver transplantation for hepatic artery thrombosis and stenosis
      in our unit with the literature. To evaluate the role of the technique in
      clinical practice. MATERIALS AND METHODS: In a two-phase 'audit cycle' study,
      adult OLT patients had Doppler studies comprising detection of HA flow and
      measurements of peak systolic velocity, resistive index and systolic acceleration
      time. In phase I, patients had Doppler examinations 'routinely' and for any
      hepatic biochemical abnormality. In phase II, Doppler ultrasound was performed
      early post-OLT and later only if a senior transplant clinician suspected graft
      ischaemia. In addition to HA measurements the waveform was visually assessed.
      Clinical outcome was the 'gold standard'. RESULTS: Phase 1: 38 patients, 40 OLT
      operations, 125 Doppler studies; 14 arteriograms. Phase 2: 35 patients, 42 OLT
      operations, two HA angioplasties, one HA revision, one non-occlusive thrombus,
      140 studies; 17 arteriograms. Results; Phase 1 [Phase 2]: sensitivity 80% [100%];
      specificity 71% [81%]; PPV 28% [56%]; NPV 96% [100%]; incidence of HA abnormality
      12.5% [19. 5%]; likelihood ratio of negative result 0.28 [0]; of positive result
      2.8 [5.3]. CONCLUSION: Previously reported results are reproducible. Normal HA
      waveform should also be a criterion of normality. The technique is very sensitive
      but relatively non-specific. Predictive values improve with discriminate use.
      MacEneaney, P. M. (2000). Clinical Radiology55, 517-524.

PMID- 10924376
TI  - Sonographic appearances of preauricular sinus.
AB  - AIM: Preauricular sinuses are a common congenital abnormality. This study was
      performed to determine their sonographic features. MATERIALS AND METHODS: Fifteen
      preauricular sinuses (in 13 patients) were examined using a 5-10 MHz transducer
      to evaluate the nature of the sinus. Surgical correlation was obtained in 11
      cases. RESULTS: Sonography detected the sinus in all cases. The maximum width of
      the sinus tract was 3 mm; it showed a branching pattern in four (27%) patients.
      Nine sinuses (60%) led to a cystic component, and the remaining six (40%) showed
      terminal ramification. Gas was identified within the sinus in nine (60%) cases.
      In the patients that underwent surgery, the diagnosis and the relationship of the
      sinus/ cystic component to the superficial temporal artery (STA), anterior crus
      of the helix and the tragus was confirmed and correlated well with the
      sonographic findings. However, the branching pattern of the sinus tract was
      difficult to confirm. CONCLUSION: Sonography readily detects preauricular sinuses
      and demonstrates their relationship to the STA, anterior crus of the helix, and
      the tragus, and can therefore be helpful in pre-operative assessment. Ahuja, A.
      T. (2000). Clinical Radiology 55, 528-532.

PMID- 10924375
TI  - D-dimer assay for deep vein thrombosis: its role with colour Doppler sonography.
AB  - AIM: To evaluate the role of a negative D-dimer assay in the initial management
      of patients with clinically suspected deep venous thrombosis (DVT), using colour
      Doppler ultrasound as the primary diagnostic technique. MATERIALS AND METHODS: A
      double-blind prospective trial was performed on 143 patients with clinically
      suspected DVT. All patients underwent a D-dimer assay prior to anticoagulant
      therapy. DVT was confirmed or excluded by diagnostic colour Doppler ultrasound
      within 24 h of presentation. RESULTS: In nearly one-third of the cases (31.8%),
      Doppler ultrasound was positive. The D-dimer assay demonstrated a sensitivity of
      97.7% with only one false-negative, but the specificity was low at 48.9% with 45
      false-positive results. The positive predictive value for D-dimer assay was
      48.8%, whilst the important negative predictive value was 98%. CONCLUSION: If D
      dimer was used to screen for DVT, and patients with negative results were not
      imaged, then the imaging workload could be reduced by 35%. In this study one
      small calf vein thrombus would have been missed by adopting this
      practice.Bradley, M. (2000). Clinical Radiology 55, 525-527.

PMID- 10924377
TI  - Duplex Doppler ultrasonography of lower limb veins: detection of cardiac
      abnormalities.
AB  - AIM: We describe the detection of right sided cardiac abnormalities by Doppler
      ultrasonography of the lower limb veins. We also attempt to quantify the degree
      of tricuspid regurgitation (TR) by analysis of the femoral vein Doppler waveform
      (DW). MATERIALS AND METHODS: The DWs of the lower limb veins were examined in 276
      patients over a 17-month period. The detection of abnormal pulsatile DW was
      compared with echocardiography on these patients. The reports of chest
      radiographs (CXR) obtained on 104 of the 276 patients were reviewed. RESULTS:
      Abnormal cardiac pulsatility of the DW was detected in nine patients (3.3%), with
      abnormally high retrograde velocity peak (RVP) recordings. These abnormal RVPs
      are compared to RVPs in a normal control group. The RVPs in the abnormal group
      revealed a statistically significant (Pearson's r = 0.9113) correlation with the
      degree of TR observed on echocardiography. All nine patients (100%) demonstrated
      cardiac enlargement on CXR compared to 16 of the 95 (16.8%) with a normal DW and
      available report of recently performed CXR. CONCLUSION: Doppler ultrasonography
      of lower limb veins is a frequently performed examination in most Radiology
      departments. We describe a simple, effective and reproducible ultrasound
      technique enabling detection of an underlying cardiac abnormality that may
      provide an estimation of the degree of TR. These important signs should alert the
      examining radiologist to the presence of an underlying cardiac dysfunction that
      may require further appropriate cardiac evaluation.McClure, M. J. (2000).
      Clinical Radiology 55, 533-536.

PMID- 10924378
TI  - An audit of MRI for bone and soft-tissue tumours performed at referral centres.
AB  - AIM: Magnetic resonance imaging (MRI) is essential in the pre-operative staging
      of suspected primary bone and soft-tissue sarcomas. Such lesions are ideally
      managed in specialist centres but it is becoming increasingly common for patients
      to undergo MRI before referral. The aim of this study was to assess the adequacy
      of such studies. MATERIALS AND METHODS: Fifty patients (30 men, 20 women; mean
      age 39 years, range 9-89 years) were included over a 1-year period. Tumours
      included 31 suspected primary bone tumours and 19 soft-tissue tumours. RESULTS:
      The total number of sequences used was 225 (mean 4, range 2-8). Enhancement was
      used in 19 cases. The commonest mistake was the failure to image the whole bone
      for 'skip' metastases in 50% of appropriate cases (high-grade malignant lesions
      of bone). Reports were available in 40 cases. Specific information regarding
      precise intraosseous and extraosseous extent of tumour and relationship to the
      neurovascular bundle and adjacent joint was commonly not included. CONCLUSIONS:
      This audit indicates that a greater awareness is needed amongst general
      radiologists of the MR imaging and reporting requirements for musculoskeletal
      tumours. In particular, all important axial imaging is sometimes
      omitted.Saifuddin, A. (2000). Clinical Radiology 55, 537-541.

PMID- 10924379
TI  - Computed tomography and ultrasound in parapneumonic effusions and empyema.
AB  - AIM: Imaging of pleural empyema by ultrasound (US) or computed tomography (CT) is
      used to confirm the diagnosis and facilitate drainage. However, the information
      gained from US and CT may also have prognostic significance. The aim of the
      present study was to determine if CT and US appearances correlated with the
      severity of infection as determined by established microbiological and
      biochemical indicators, and to establish whether either technique could predict
      those patients who will fail drainage and require surgery. MATERIALS AND METHODS:
      Fifty patients with parapneumonic effusions were assessed. All had thoracic CT
      and the results of thoracic US were available in 36 patients. Imaging features
      were compared to the stage of the effusion and clinical outcome. RESULTS: At US,
      7/36 (19%) pleural collections were anechoic, 5/36 (14%) were hyperechoic without
      septae and 24/36 (67%) were hyperechoic with septae. There was no relationship
      between US appearances and the presence of pus, the effusion stage or the need
      for surgical treatment. On CT pleural enhancement was seen in all patients. There
      was evidence of pleural thickening in 46/50 (92%) and thickening of extrapleural
      fat in 38/50 (76%). There was a trend for mean pleural thickness to increase with
      an increasing stage of pleural infection. However, a wide range of appearances
      were seen and overall the thickness of pleural/extrapleural tissues was not
      significantly related to the stage of effusion or to the requirement for surgery.
      CONCLUSIONS: Although US and CT have established roles in the investigation of
      parapneumonic effusions, neither technique reliably identifies the stage of
      pleural infection or predicts those patients who subsequently require surgical
      intervention after failed management by chest tube drainage and intrapleural
      fibrinolytics. Kearney, S. E. (2000). Clinical Radiology 55, 542-547.

PMID- 10924381
TI  - An evaluation of computed tomography as an aid to diagnosis in patients
      undergoing bronchoscopy for suspected bronchial carcinoma.
AB  - AIM: To determine whether computed tomography (CT) can predict the likelihood of
      obtaining a positive tissue diagnosis at fibreoptic bronchoscopy (FOB), or
      demonstrate an alternative means of achieving a tissue diagnosis, in patients
      presenting with a high clinical suspicion of primary bronchogenic carcinoma and
      an abnormal chest radiograph (CXR). MATERIALS AND METHODS: Sixty-two patients
      presenting with a high clinical suspicion of carcinoma and an abnormal CXR had
      chest and liver CT and FOB performed. All patients subsequently had
      histocytological confirmation of malignancy. Features recorded from the CTs
      included: the site and characteristics of a mass if present, and its relationship
      to adjacent airways; the presence of presumed metastatic disease; and a CT
      prediction of the likelihood of positive FOB was made. RESULTS: Of the patients,
      41/62 (66%) had inoperable stage IIIb/IV disease. Fibreoptic biopsy yielded
      positive tissue diagnoses in 38/62 (61%). Computed tomography features predicting
      a positive FOB in this group included: ill-definition of the mass (12/15, 80%); a
      mass <4 cm from the origin of the nearest lobar bronchus (36/53, 68%); an
      endobronchial component of mass (22/24, 92%); a segmental or larger airway
      leading to the mass (30/35, 86%). Overall, CT had positive and negative
      predictive values for positive FOB of 85% and 78% respectively. The accuracy of
      the overall CT prediction of positive FOB was better than the accuracy of any of
      the individual factors. Seventeen of 62 (27%) patients had presumed metastatic
      disease suitable for percutaneous biopsy. CONCLUSION: Computed tomography is
      useful in predicting the likelihood of achieving positive histocytology at FOB.
      The overall CT prediction is superior to any of the individual CT features taken
      alone.Bungay, H. K. (2000). Clinical Radiology 55, 554-560.

PMID- 10924380
TI  - When have mammographic calcifications been adequately sampled at needle core
      biopsy?
AB  - AIMS: To determine if the number of flecks of calcification retrieved at
      stereotaxic core needle biopsy or the number of core samples obtained containing
      calcification are related to biopsy sensitivity, and to determine how many
      calcifications or cores containing calcification the radiologist should aim to
      retrieve when sampling mammographic microcalcification. MATERIALS AND METHODS: A
      retrospective review was performed of core specimen radiographs from 57
      consecutive patients who had stereotaxic core needle biopsies of impalpable
      malignant microcalcifications without an associated mammographic mass. The total
      number of calcifications retrieved and the numbers of cores containing
      calcification were correlated with findings at core and surgical histology.
      RESULTS: Increasing retrieval of calcification elements visible on specimen
      radiography was associated with increasing sensitivity of the biopsy. Five or
      more flecks of calcium gave an absolute sensitivity of 100%. Increasing numbers
      of core samples obtained containing radiographically demonstrable calcification
      was also associated with increasing sensitivity. Three or more cores containing
      calcium resulted in a 100% absolute sensitivity for malignancy. CONCLUSION: To
      ensure adequate sampling of calcification at core biopsy, an optimum of either
      three or more cores containing calcium or five or more flecks of calcium in total
      is required. Achieving this target ensures a high pre-operative diagnosis rate
      for malignant microcalcifications.Bagnall, M. J. C. (2000). Clinical Radiology
      55, 548-553.

PMID- 10924382
TI  - Digital radiography in the evaluation of oesophageal motility disorders.
AB  - AIMS: To develop a simple technique for examination of the oesophagus by digital
      radiography and to assess its role in the evaluation of motility disorders of the
      oesophagus. MATERIALS AND METHODS: Forty-nine patients and 44 control subjects
      underwent manometry and digital examination of the oesophagus. The digital study
      consisted of two parts: firstly examination of the pharynx and cervical
      oesophagus using 15 ml of fluid barium in anterio-posterior (AP) and lateral
      views, with image acquisition of four frames/s for 2 s. Secondly, examination of
      the thoracic oesophagus and oesophagogastric junction using 25 ml of barium in
      two prone oblique and one supine AP series, with image acquisition of one frame/s
      for 20 s. Oesophageal transit time (OTT) was measured in each case. Abnormal or
      non-peristaltic contractions were described regarding their morphology, time of
      visualization and length. The presence or absence of hiatal hernia, reflux or any
      associated organic lesions was noted. RESULTS: Digital radiography diagnosed 14
      cases of achalasia and 28 cases of non-specific oesophageal motility disorder
      (NOMD). Normal OTT was 11.95 +/- 1.304 s. The OTT was prolonged (16 s or more) in
      all patients except five; four of these were cases of NOMD. Abnormal contractions
      were classified into circular and longitudinal types. The circular non
      obliterating type was commoner. Achalasia was diagnosed in all cases, as failure
      of relaxation of the inferior oesophageal sphincter was always present and easily
      depicted by digital radiography. Abnormal contractions in the body of the
      oesophagus were elicited in 57% of cases of achalasia. The sensitivity of digital
      radiography in detecting oesophageal motility disorders was 85.7% based on the
      presence of abnormal contractions and 91.6% by eliciting a prolonged OTT.
      CONCLUSIONS: Examination of the oesophagus by digital radiography is simple, non
      invasive, reproducible, rapid and without discomfort to patients. It allows the
      diagnosis of motility disorders of the oesophagus by detecting abnormal
      contractions and/or prolonged OTT and showed any associated organic lesions.Aly,
      Y. A. (2000). Clinical Radiology 55, 561-568.

PMID- 10924383
TI  - Cervical pneumorrhachis.

PMID- 10924384
TI  - MR appearance of metastatic melanotic melanoma in the breast.

PMID- 10924386
TI  - The diagnostic accuracy of magnetic resonance cholangiopancreatography (MRCP) and
      ultrasound compared with direct cholangiography in the detection of
      choledocholithiasis.

PMID- 10924385
TI  - Imaging appearances of pseudoangiomatous hyperplasia of mammary stroma.

PMID- 10924387
TI  - Sheep blowfly strike: a model approach.

PMID- 10924388
TI  - Veterinary advances in the investigation of wildlife diseases in Britain.

PMID- 10924389
TI  - Marek's disease: an update on oncogenic mechanisms and control.
AB  - Marek's disease (MD) is a common lymphoproliferative disease of poultry caused by
      a highly contagious and oncogenic herpesvirus. In spite of the widespread use of
      highly effective MD vaccines, recently there have been worrying trends in the
      evolution of MD virus pathotypes towards greater virulence. In the last few
      years, there has been significant progress in determining the molecular structure
      of MD virus and several genes that map within the repeat regions of the virus,
      such as Bam HI-H family, ICP 4, meq and pp38, which are potentially associated
      with the latency and transformation have been identified. The functions of some
      of these genes have provided insights into the mechanisms of MD virus-induced
      oncogenesis. This review summarises some of these oncogenic mechanisms and the
      progress in the control of MD.

PMID- 10924390
TI  - Gene expression in the forebrain of dexamethasone-treated pigs: effects on stress
      neuropeptides in the hypothalamus and hippocampus and glutamate receptor subunits
      in the hippocampus.
AB  - Gene expression studies advance our understanding of the effects of stress and
      glucocorticoids on brain function and give a new direction to animal welfare
      research. In this context, the presence of messenger RNA s (m RNA s) for
      corticotrophin releasing hormone (CRH) and vasopressin (VP) in the porcine
      hypothalamus has recently been documented. This study investigated the expression
      of CRH, VP and ionotropic glutamate receptor (iGluR) subunit m RNA s in the
      brains of pigs treated with the synthetic glucocorticoid dexamethasone (Dex; 5 mg
      kg(-1)i.v.). In the hypothalamus, VP, but not CRH, m RNA was reduced 3 hours
      after Dex. In the hippocampus, expression of m RNA s for some iGluR subunits
      appeared to be differentially regulated 6 hours after Dex. In addition, CRH
      message was detected in the hippocampus and significantly upregulated in the CA1
      region 3 hours after Dex. The relevance of these findings to stress neurobiology
      of the growing pig is discussed.

PMID- 10924391
TI  - The effect of sex and age on caffeine pharmacokinetics in cattle.
AB  - The aim of this study was to determine the effect of sex on the pharmacokinetics
      of caffeine in cattle at different ages. Ten female and 10 male Holstein cattle
      were subject to a caffeine test when they were aged 1, 2, 4, 6, 8, 12 and 18
      months. Caffeine, 5 mg kg(-1)body weight, was given intravenously as a sterile
      isotonic solution. An automated, enzyme-multiplied, immunoassay technique (EMIT)
      was used to determine plasma caffeine concentration. The volume of distribution
      of caffeine (V(SS)) decreased significantly between 1 and 18 months of life. Mean
      V(SS)values observed in males and females were not statistically different. The
      experimental period was characterised by a steady decrease (statistically
      significant) in caffeine mean residence time (MRT). These values did not differ
      significantly between males and females under 8 months of age. In 8-, 12- and 18
      month-old animals, the caffeine MRT in the females was significantly shorter than
      in the males. The total plasma clearance (Cl(tot)) of caffeine increased
      significantly between 1 and 18 months of age. No significant differences were
      observed between total plasma clearance of caffeine in males and females under 8
      months of age. In 8-, 12- and 18-month-old animals, the Cl(tot)of caffeine was
      significantly higher in females than in males. In conclusion, we report a sex
      linked difference in pharmacokinetics of caffeine in cattle over 8 months of age,
      the females being the more active metabolisers. The results of the present study
      support the hypothesis that the metabolism of xenobiotics is sexually different
      in ruminants.

PMID- 10924392
TI  - Isolation and characterisation of fetal bovine brain cells in primary culture.
AB  - Primary cultures and cryopreservation procedure of bovine brain cells were
      established as in vitro experimental systems to study the responses of bovine
      brain cells to neuropathogenic agents. Brain cells were dissociated by papain
      from the cerebellum of a bovine fetus at 90 to 120 days old, and were cultured in
      different media. In a medium containing 1 per cent fetal bovine serum (FBS),
      neuronal cells were maintained and they formed clusters on glial and fibroblastic
      cell sheets. In a medium containing 10 per cent FBS, the proportion of neurones
      decreased, and fibroblastic and microglial cells dominated. In a serum-free
      medium containing epidermal growth factor, the highest neuronal proportion was
      obtained. Optimal cryopreservation condition for the brain tissues was
      investigated by changing the concentrations of DMSO and FBS. Brain cells could be
      cultured from cryopreserved tissue with only slightly reduced growth profiles and
      varying cell proportions in comparison to those prepared from fresh tissue.

PMID- 10924394
TI  - Effect of current frequency during electrical stunning in a water bath on
      somatosensory evoked responses in turkey's brain.
AB  - Somatosensory evoked responses (SEP) in a turkey's brain were determined after
      water-bath stunning with a 150-mA (constant current) delivered with 50, 300 or
      600 Hz, or with 75 mA, delivered with 50-Hz alternating current (AC) in order to
      evaluate the effectiveness of stunning. Ninety-four BUT 9 turkey hens 12 weeks of
      age were surgically implanted with EEG recording and left wing nerve stimulating
      electrodes 4 hours before stunning. They were individually stunned by immersion
      of the head and upper part of the neck in a water bath for 4 s. Using a 150-mA
      current, all birds stunned at 50 Hz showed cardiac arrest and a flat EEG
      immediately after the stun with no SEP recovery. The incidence of cardiac arrest
      at stunning decreased with increasing current frequency but SEP were lost in all
      birds. In birds that survived the stun, the duration of SEP abolition was on
      average 69 and 34 seconds at 300 and 600 Hz, respectively. Stunning with a 75-mA
      AC, delivered with 50 Hz, induced cardiac arrest in 32 per cent of turkeys. SEP
      were abolished in only 71 per cent of the birds that survived the stun, with an
      average duration of SEP of 66 seconds. The results indicate that increasing the
      frequency of a 150-mA AC current leads to a decreased stunning efficiency. A
      current of 75 mA per bird is unacceptable since 29 per cent of the birds do not
      show SEP abolition.

PMID- 10924393
TI  - A pilot study of protein sparing in healthy dogs using peripheral parenteral
      nutrition.
AB  - Total parenteral nutrition is the standard nutritional support of dogs when the
      enteral route is contraindicated, but it can be difficult because of cost,
      technical difficulties, and potential complications. Peripheral parenteral
      nutrition (PPN) may be a feasible option for short-term support in some cases.
      The objectives of this study were to determine the effect of PPN on nitrogen
      balance (as an indicator of the effect on protein sparing), serum folate
      concentrations and serum insulin-like growth factor-I (IGF - I) concentrations in
      fasting dogs. The effect of PPN on these parameters has not previously been
      reported in dogs. Using a cross-over design, three healthy adult fasting dogs
      were randomly assigned to three treatments: 5 per cent amino acid solution, 5 per
      cent glucose solution, and a control electrolyte solution. The solutions were
      administered into a peripheral vein at 60 ml kg(-1)per day for 4 days. The amino
      acid infusion resulted in a positive nitrogen balance and the glucose infusion
      produced less nitrogen loss than the control. Amino acid, but not glucose or
      electrolyte infusions, decreased serum folate concentrations. Amino acid and
      glucose infusions resulted in higher serum IGF -I concentrations than electrolyte
      infusions, although the differences were small and IGF -I decreased in all cases.
      In conclusion, these findings suggest that PPN increases nitrogen balance in
      healthy dogs undergoing short-term fasting.

PMID- 10924395
TI  - An evaluation of the gamma interferon test for detecting bovine tuberculosis in
      cattle 8 to 28 days after tuberculin skin testing.
AB  - The gamma interferon (IFN -gamma) test was evaluated for its ability to diagnose
      bovine tuberculosis in cattle that 8 to 28 days previously had a positive caudal
      fold skin test. The sensitivity of the test was determined in a group of 163
      Mycobacterium bovis -infected cattle from 21 herds. The specificity was estimated
      in a group of 213 cattle which had reacted to a caudal fold test, but were from
      82 herds that had no evidence of infection with M bovis. The sensitivity and
      specificity of the IFN -gamma test was 85 and 93 per cent respectively. No
      significant differences in the sensitivity and specificity of the test were
      observed between blood samples that were cultured on the day of collection and
      those cultured the day after collection. These findings support the use of the
      IFN -gamma test as a practical serial test that can be used to complement the
      caudal fold skin test.

PMID- 10924396
TI  - Differences in the concentration of various synovial fluid constituents between
      the distal interphalangeal joint, the metacarpophalangeal joint and the navicular
      bursa in normal horses.
AB  - As a prerequisite for the identification of navicular disease markers, the
      concentrations of cartilage oligomeric matrix protein (COMP), total
      glycosaminoglycans (GAG), hyaluronan, metalloproteinases (MMP) 2 and 9 and total
      protein were measured in synovial fluid samples obtained from the distal
      interphalangeal joint (DIP), the metacarpophalangeal joint (MCP) and the
      navicular bursa of 24 horses. Mean GAG, COMP and total protein levels were
      significantly higher in the DIP joint and in the navicular bursa compared to the
      MCP joint. Hyaluronan content was lower. MMP -2 activity was present in all
      fluids measured and had similar levels in different joints. MMP -9 was present in
      42 per cent of MCP joint samples and 58 per cent of DIP joint samples and of
      navicular bursal samples. In relation to the constituents measured, the
      composition of navicular bursal fluid was similar to the articular synovial
      fluids, in particular that obtained from the DIP joint. Correlation between the
      constituents of DIP joint fluid and navicular bursal fluid obtained from the same
      legs was statistically significant for all the parameters measured.

PMID- 10924397
TI  - The pharmacokinetics, metabolism and urinary detection time of caffeine in
      camels.
AB  - The pharmacokinetics of caffeine were determined in 10 camels after an
      intravenous dose of 2.35 mg kg(-1). The data obtained (median and range) were as
      follows. The elimination half-life (t(1/2)) was 31.4 (21.2 to 58.9) hours, the
      steady state volume of distribution (V(SS)) was 0.62 (0.51 to 0.74) litre kg(
      1)and the total body clearance (Cl(T)) was 14.7 (8.70 to 19.7) ml kg(-1)per hour.
      Renal clearance estimated in two camels was 0.62 and 0.34 ml kg(-1)per hour. In
      vitro plasma protein binding (mean +/-SEM, n = 10) to a concentration of 2 and 8
      microg ml(-1)was 36.0 +/- 0.24 and 39.2 +/- 0.36 per cent respectively.
      Theophylline and theobromine were identified as caffeine metabolites in serum and
      urine. The terminal elimination half-life of the former, estimated in two camels,
      was 70. 4 and 124.4 hours. Caffeine could be detected in the urine for 14 days.

PMID- 10924398
TI  - The relationships between social behaviour of dairy cows and the occurrence of
      lameness in three herds.
AB  - It is well known that lameness in cattle has a multifactorial causation, however
      it is still not clear why some individuals are more susceptible to foot lesions
      in the same environment. Behaviour is thought to play an important role. The aim
      of this study was to assess the relationships between social and individual
      behaviour and the incidence of lameness in three dairy herds. Low-ranking cows
      spent less time lying and more time standing still and standing half in the
      cubicles than middle- and high-ranking cows. As time spent standing half in the
      cubicle increased, the number of soft tissue lesions increased and as total time
      standing increased the number of cases of lameness increased. The survival rate
      to lameness for low-ranking cows was significantly lower than for middle- or high
      ranking individuals.

PMID- 10924399
TI  - Dietary effects on bone quality and turnover, and Ca and P metabolism in
      chickens.
AB  - The responses of skeletal health and blood calcium (Ca) and phosphorus (P) status
      to different dietary calcium and available P (avP) contents were examined in 2
      week-old chickens. High avP content resulted in more inorganic P (P(i)) and less
      ionised Ca (Ca(2+)) in the blood. Birds on low Ca and high avP diets showed a
      higher incidence of tibial dyschondroplasia and hypocalcaemic rickets and were
      therefore assumed to be hypocalcaemic. However the molar Ca:P ratio in bone was
      closer to the expected 1.67:1 in diets high in avP. No significant dietary
      mineral content effect was found on bone mineral content, or breaking strength,
      within the range of diets used. Results suggest that variations in molar Ca:P
      ratios in bone have little effect on mechanical competence, and that diets for
      this strain should be higher in Ca, and could be lower in avP, than current
      recommendations.

PMID- 10924400
TI  - Effect of clinoptilolite on serum biochemical and haematological characters of
      broiler chickens during aflatoxicosis.
AB  - Clinoptilolite (CLI, a natural zeolite) incorporated into the diet at 1.5 and 2.5
      per cent were evaluated for their ability to reduce the deleterious effects of
      2.5 mg total aflatoxin (AF) kg(-1)diet on broiler chickens from 1 to 21 days of
      age. In total 360 broiler chicks were divided into six equal treatment groups
      (control, AF, CLI (1.5 per cent), AF plus CLI (1.5 per cent), CLI (2.5 per cent)
      and AF plus CLI (2.5 per cent)). When compared with the controls, AF treatment
      significantly decreased serum total protein, albumin, inorganic phosphorus, uric
      acid, total cholesterol and the values of haematocrit, red blood cell counts,
      mean corpuscular volume, haemoglobin, thrombocyte counts, percentage of monocyte
      counts; increased values of white blood cell and heterophil counts. The addition
      of CLI (1.5 per cent) and CLI (2.5 per cent) to the AF -containing diet reduced
      the adverse effects of AF and should be helpful in a solution to the
      aflatoxicosis problem in poultry.

PMID- 10924401
TI  - Serum and milk lactoferrin concentration and the correlation with some blood
      components in lactating sows.
AB  - An increased serum concentration of lactoferrin is associated with inflammatory
      disease, but there are few reported data on this aspect for lactating sows.
      Samples of blood and milk were collected from 17 lactating sows under minimum
      stress conditions and analysed for lactoferrin. Lactoferrin concentrations in
      serum and milk were positively correlated, being high after farrowing and
      steadily decreasing throughout 28 days of lactation. A positive linear
      correlation was observed between lactoferrin concentration and enzyme activities
      of alanine aminotransferase, lactate dehydrogenase, and hydroxybutyrate
      dehydrogenase in the serum indicating post-partum inflammation. Serum and milk
      lactoferrin concentrations, although closely correlated, may be regulated through
      independent systems activated simultaneously.

PMID- 10924402
TI  - Rapid molecular typing of Listeria monocytogenes by pulsed-field gel
      electrophoresis.
AB  - Pulsed-field gel electrophoresis (PFGE) is a highly discriminating tool for
      molecular typing, but the conventional PFGE protocol is time consuming. This
      paper describes a rapid method of PFGE for Listeria monocytogenes that yields
      results within 2 days.

PMID- 10924403
TI  - mtDNA variation among Greenland Eskimos: the edge of the Beringian expansion.
AB  - The Eskimo-Aleut language phylum is distributed from coastal Siberia across
      Alaska and Canada to Greenland and is well distinguished from the neighboring Na
      Dene languages. Genetically, however, the distinction between Na Dene and Eskimo
      Aleut speakers is less clear. In order to improve the genetic characterization of
      Eskimos in general and Greenlanders in particular, we have sequenced
      hypervariable segment I (HVS-I) of the mitochondrial DNA (mtDNA) control region
      and typed relevant RFLP sites in the mtDNA of 82 Eskimos from Greenland. A
      comparison of our data with published sequences demonstrates major mtDNA types
      shared between Na Dene and Eskimo, indicating a common Beringian history within
      the Holocene. We further confirm the presence of an Eskimo-specific mtDNA
      subgroup characterized by nucleotide position 16265G within mtDNA group A2. This
      subgroup is found in all Eskimo groups analyzed so far and is estimated to have
      originated <3,000 years ago. A founder analysis of all Eskimo and Chukchi A2
      types indicates that the Siberian and Greenland ancestral mtDNA pools separated
      around the time when the Neo-Eskimo culture emerged. The Greenland mtDNA types
      are a subset of the Alaskan mtDNA variation: they lack the groups D2 and D3 found
      in Siberia and Alaska and are exclusively A2 but at the same time lack the A2
      root type. The data are in agreement with the view that the present Greenland
      Eskimos essentially descend from Alaskan Neo-Eskimos. European mtDNA types are
      absent in our Eskimo sample.

PMID- 10924404
TI  - Multicenter linkage study of schizophrenia candidate regions on chromosomes 5q,
      6q, 10p, and 13q: schizophrenia linkage collaborative group III.
AB  - Schizophrenia candidate regions 33-51 cM in length on chromosomes 5q, 6q, 10p,
      and 13q were investigated for genetic linkage with mapped markers with an average
      spacing of 5.64 cM. We studied 734 informative multiplex pedigrees (824
      independent affected sibling pairs [ASPs], or 1,003 ASPs when all possible pairs
      are counted), which were collected in eight centers. Cases with diagnoses of
      schizophrenia or schizoaffective disorder (DSM-IIIR criteria) were considered
      affected (n=1,937). Data were analyzed with multipoint methods, including
      nonparametric linkage (NPL), ASP analysis using the possible-triangle method, and
      logistic-regression analysis of identity-by-descent (IBD) sharing in ASPs with
      sample as a covariate, in a test for intersample heterogeneity and for linkage
      with allowance for intersample heterogeneity. The data most supportive for
      linkage to schizophrenia were from chromosome 6q; logistic-regression analysis of
      linkage allowing for intersample heterogeneity produced an empirical P value
      <.0002 with, or P=.0004 without, inclusion of the sample that produced the first
      positive report in this region; the maximum NPL score in this region was 2.47
      (P=.0046), the maximum LOD score (MLS) from ASP analysis was 3.10 (empirical
      P=.0036), and there was significant evidence for intersample heterogeneity
      (empirical P=.0038). More-modest support for linkage was observed for chromosome
      10p, with logistic-regression analysis of linkage producing an empirical P=. 045
      and with significant evidence for intersample heterogeneity (empirical P=.0096).

PMID- 10924405
TI  - Segregation analysis of phenotypic components of learning disabilities. I.
      Nonword memory and digit span.
AB  - Dyslexia is a common and complex disorder with evidence for a genetic component.
      Multiple loci (i.e., quantitative-trait loci [QTLs]) are likely to be involved,
      but the number is unknown. Diagnosis is complicated by the lack of a standard
      protocol, and many diagnostic measures have been proposed as understanding of the
      component processes has evolved. One or more genes may, in turn, influence these
      measures. To date, little work has been done to evaluate the mode of inheritance
      of individual component-as opposed to composite-phenotypes, beyond family or twin
      correlation studies that initially demonstrate evidence for a genetic basis of
      such components. Here we use two approaches to segregation analysis in 102
      nuclear families to estimate genetic models for component phenotypes associated
      with dyslexia: digit span and a nonword-repetition task. Both measures are
      related to phonological skills, one of the key component processes in dyslexia.
      We use oligogenic-trait segregation analysis to estimate the number of QTLs
      contributing to each phenotype, and we use complex segregation analysis to
      identify the most parsimonious inheritance models. We provide evidence in support
      of both a major-gene mode of inheritance for the nonword-repetition task, with
      approximately 2.4 contributing QTLs, and for a genetic basis of digit span, with
      approximately 1.9 contributing QTLs. Results obtained by reciprocal adjustment of
      measures suggest that genes contributing to digit span may contribute to the
      nonword-repetition score but that there are additional QTLs involved in nonword
      repetition. Our study adds to existing studies of the genetic basis of composite
      phenotypes related to dyslexia, by providing evidence for major-gene modes of
      inheritance of these single-measure component phenotypes.

PMID- 10924406
TI  - Identification and analysis of error types in high-throughput genotyping.
AB  - Although it is clear that errors in genotyping data can lead to severe errors in
      linkage analysis, there is as yet no consensus strategy for identification of
      genotyping errors. Strategies include comparison of duplicate samples,
      independent calling of alleles, and Mendelian-inheritance-error checking. This
      study aimed to develop a better understanding of error types associated with
      microsatellite genotyping, as a first step toward development of a rational error
      detection strategy. Two microsatellite marker sets (a commercial genomewide set
      and a custom-designed fine-resolution mapping set) were used to generate 118,420
      and 22,500 initial genotypes and 10,088 and 8,328 duplicates, respectively.
      Mendelian-inheritance errors were identified by PedManager software, and
      concordance was determined for the duplicate samples. Concordance checking
      identifies only human errors, whereas Mendelian-inheritance-error checking is
      capable of detection of additional errors, such as mutations and null alleles.
      Neither strategy is able to detect all errors. Inheritance checking of the
      commercial marker data identified that the results contained 0.13% human errors
      and 0.12% other errors (0.25% total error), whereas concordance checking found
      0.16% human errors. Similarly, Mendelian-inheritance-error checking of the custom
      set data identified 1.37% errors, compared with 2.38% human errors identified by
      concordance checking. A greater variety of error types were detected by Mendelian
      inheritance-error checking than by duplication of samples or by independent
      reanalysis of gels. These data suggest that Mendelian-inheritance-error checking
      is a worthwhile strategy for both types of genotyping data, whereas fine-mapping
      studies benefit more from concordance checking than do studies using commercial
      marker data. Maximization of error identification increases the likelihood of
      linkage when complex diseases are analyzed.

PMID- 10924407
TI  - Characterization of terminal deletions at 7q32 and 22q13.3 healed by De novo
      telomere addition.
AB  - We have developed a strategy for the isolation of terminal deletion breakpoints
      from any chromosome that has been healed by de novo addition of a telomere repeat
      array. Breakpoints at 7q32 and 22q13.3 have been isolated and characterized in
      two patients (patients FB336R and AJ). Both truncated chromosomes have been
      healed by the addition of a novel telomere, with such an addition possibly
      mediated by the enzyme telomerase. The breakpoint at 7q32 in patient FB336R shows
      a structure similar to that of breakpoints on other chromosomes that have been
      healed in this way. However, the breakpoint at 22q13.3 in patient AJ has 10
      nucleotides of unknown origin inserted between the sequence unique to chromosome
      22q and the start of the telomere repeat array. This unusual structure is
      suggestive of a multistep healing event resulting in de novo telomere addition at
      this breakpoint, and possible mechanisms are discussed.

PMID- 10924408
TI  - Familial aggregation of absolute pitch.
AB  - Absolute pitch (AP) is a behavioral trait that is defined as the ability to
      identify the pitch of tones in the absence of a reference pitch. AP is an ideal
      phenotype for investigation of gene and environment interactions in the
      development of complex human behaviors. Individuals who score exceptionally well
      on formalized auditory tests of pitch perception are designated as "AP-1." As
      described in this report, auditory testing of siblings of AP-1 probands and of a
      control sample indicates that AP-1 aggregates in families. The implications of
      this finding for the mapping of loci for AP-1 predisposition are discussed.

PMID- 10924411
TI  - This month in wjm

PMID- 10924410
TI  - Editor's pick

PMID- 10924409
TI  - Inactivation of germline mutant APC alleles by attenuated somatic mutations: a
      molecular genetic mechanism for attenuated familial adenomatous polyposis.
AB  - Germline mutations of the adenomatous polyposis coli (APC) tumor-suppressor gene
      result in familial adenomatous polyposis (FAP). Patients with FAP typically
      develop hundreds to thousands of benign colorectal tumors and early-onset
      colorectal cancer. A subset of germline APC mutations results in an attenuated
      FAP (AFAP) phenotype, in which patients develop fewer tumors and develop them at
      an older age. Although a genotype-phenotype correlation between the locations of
      APC germline mutations and the development of AFAP has been well documented, the
      mechanism for AFAP has not been well defined. We investigated the mechanism for
      AFAP in patients carrying a mutant APC allele (APC(AS9)) that has a mutation in
      the alternatively spliced region of exon 9. APC(AS9) was found to down-regulate
      beta-catenin-regulated transcription, the major tumor-suppressor function of APC,
      as did the wild-type APC. Mutation analysis showed that both APC(AS9) and the
      wild-type APC alleles were somatically mutated in most colorectal tumors from
      these patients. Functional analysis showed that 4666insA, a common somatic
      mutation in APC(AS9) in these tumors, did not inactivate the wild-type APC. Our
      results indicate that carriers of APC(AS9) develop fewer colorectal tumors than
      do typical patients with FAP because somatic inactivation of both APC alleles is
      necessary for colorectal tumorigenesis. However, these patients develop
      colorectal tumors more frequently than does the general population because
      APC(AS9) is inactivated by mutations that do not inactivate the wild-type APC.

PMID- 10924412
TI  - The male menopause: does it exist?: for: some men need investigation and
      testosterone treatment

PMID- 10924413
TI  - The male menopause: does it exist?: against: problems of senescence in men are
      not analogous to female menopause

PMID- 10924414
TI  - "Manopause"

PMID- 10924415
TI  - US physicians may be failing to recognize substance misuse.

PMID- 10924416
TI  - Gangrene bug killed 35 heroin users.

PMID- 10924417
TI  - California researchers receive highest number of FDA warnings.

PMID- 10924419
TI  - Global news roundup

PMID- 10924418
TI  - California doctors' leaders sue health insurers.

PMID- 10924420
TI  - The sum of my parts

PMID- 10924421
TI  - A memorable patient

PMID- 10924422
TI  - Fatal asthma in a child after use of an animal shampoo containing pyrethrin.

PMID- 10924423
TI  - Blaming the commentator.

PMID- 10924425
TI  - A film to make you think

PMID- 10924424
TI  - Marital status and physician-assisted suicide.

PMID- 10924427
TI  - Smoke alarms and prevention of house-fire-related deaths and injuries.

PMID- 10924426
TI  - Ionization and photoelectric smoke alarms in rural Alaskan homes.
AB  - OBJECTIVE: To compare rates of nuisance alarms and disconnection between
      ionization and photoelectric smoke alarms. DESIGN: A prospective cohort study.
      SETTING: Four Inupiat Eskimo villages in the Northwest Arctic Borough region of
      Alaska, 48 km (30 mi) above the Arctic Circle. SUBJECTS: Households in 4
      communities with similar populations, number of homes, mean income, size of
      household, and square footage per home. INTERVENTION: Two villages had
      photoelectric alarms installed (58 homes), and 2 other villages had ionization
      alarms installed (65 homes) in standard locations. Follow-up household surveys
      were conducted after 6 months to determine rates of false alarms and detector
      disconnection. All of the households that could be contacted 104/123 agreed to
      participate in the follow-up surveys. Main outcome measures The proportion of
      households experiencing false alarms and the proportion of disabled alarms in
      households in each of the test communities. RESULTS: Homes with ionization alarms
      had more than 8 times the rate of false alarms as those with photoelectric
      alarms. Eleven of the ionization alarms (19%) were disconnected compared with 2
      of the photoelectric devices (4%). CONCLUSIONS: In small rural residences,
      photoelectric smoke alarms have lower rates of false alarms and disconnection.
      Photoelectric alarms may be the preferred choice for dwellings with limited
      living space or frequent false alarms.

PMID- 10924429
TI  - Magnetic field exposure may not have a directly causal relationship to suicide.

PMID- 10924428
TI  - Exposure to electromagnetic fields and suicide among electric utility workers: a
      nested case-control study.
AB  - OBJECTIVE: To examine mortality from suicide in relation to estimated exposure to
      extremely low-frequency electromagnetic fields in a cohort of 138,905 male
      electric utility workers. METHODS: Case-control sampling, which included 536
      deaths from suicide and 5, 348 eligible controls. Exposure was classified based
      on work in the most common jobs with increased exposure to magnetic fields and
      indices of cumulative exposure to magnetic fields based on a measurement survey.
      RESULTS: Suicide mortality was increased relative to work in exposed jobs and
      with indices of exposure to magnetic fields. Increased odds ratios (ORs) were
      found for years of employment as an electrician (OR, 2.18; 95% confidence
      interval [CI], 1.25-3.80) or line worker (OR, 1.59; 95% CI, 1.18-2.14), whereas a
      decreased OR was found for power plant operators (OR, 0.67; 95% CI, 0.33-1.40). A
      dose-response gradient with exposure to magnetic fields was found for exposure in
      the previous year, with a mortality OR of 1.70 (95% CI, 1.00-2.90) in the highest
      exposure category. Stronger associations, with ORs in the range of 2.12 to 3.62,
      were found for men younger than 50 years. CONCLUSIONS: These data provide
      evidence for an association between occupational electromagnetic fields and
      suicide that warrants further evaluation. A plausible mechanism related to
      melatonin and depression provides a direction for additional laboratory research
      and epidemiologic evaluation.

PMID- 10924431
TI  - Can we make any recommendations about physical activity and peptic ulcer disease?

PMID- 10924430
TI  - Physical activity and peptic ulcers. Does physical activity reduce the risk of
      developing peptic ulcers?
AB  - BACKGROUND: Although Helicobacter pylori has been identified as a major cause of
      chronic gastritis, not all infected patients develop ulcers, suggesting that
      other factors such as lifestyle may be critical to the development of ulcer
      disease. OBJECTIVE: To investigate the role physical activity may play in the
      incidence of peptic ulcer disease. METHODS: The participants were men (n = 8,529)
      and women (n = 2,884) who attended the Cooper Institute for Aerobics Research,
      Dallas, Texas, between 1970 and 1990. The presence of gastric or duodenal ulcer
      disease diagnosed by a physician was determined from a mail survey in 1990.
      Participants were classified into 3 physical activity groups according to
      information provided at the baseline clinic visit (before 1990): active, those
      who walked or ran 10 miles or more a week; moderately active, those who walked or
      ran less than 10 miles a week or did another regular activity; and the referent
      group consisting of those who reported no regular physical activity. RESULTS:
      With the use of gender-specific proportional hazards regression models that could
      be adjusted for age, smoking, alcohol use, body mass index, and self-reported
      tension, active men had a significantly reduced risk for duodenal ulcers
      (relative hazard [95% confidence interval] for the active group, 0.38 [0.15
      0.94], and 0.54 [0.30-0.96] for the moderately active group). No association was
      found between physical activity and gastric ulcers for men or for either type of
      ulcer for women. CONCLUSION: Physical activity may provide a nonpharmacologic
      method of reducing the incidence of duodenal ulcers among men.

PMID- 10924432
TI  - Are adolescents being screened for sexually transmitted diseases?
AB  - OBJECTIVES: To determine the proportion of sexually experienced African American
      adolescents who report having been screened for sexually transmitted diseases and
      to determine the proportion who report having been screened for these diseases
      among adolescents who have had a preventive primary health care visit in the past
      2 years. METHODS: A telephone survey of a population-based sample of African
      American adolescents aged 12 to 17 years residing in a low-income neighborhood in
      San Francisco with a high prevalence of sexually transmitted diseases. RESULTS:
      Of the 302 adolescents surveyed, 118 (39.1%) reported a history of sexual
      intercourse. Of these, 17 (26. 2%) of 65 males and 31 (58.5%) of 53 females had
      been screened for a sexually transmitted disease in the previous 12 months.
      Twenty (30. 8%) of the males and 32 (60.4%) of the females had been screened for
      a sexually transmitted disease in the previous 24 months. Of the 93 participants
      who had a preventive primary care visit since their first episode of sexual
      intercourse, 14 (26.4%) of the 53 males and 24 (60.0%) of the 40 females had been
      screened for a sexually transmitted disease in the previous 24 months.
      CONCLUSIONS: Sexually experienced African American adolescents in San Francisco
      are being screened for sexually transmitted diseases at rates well below those
      recommended by current clinical guidelines. A low rate of screening was found
      even in adolescents who had been seen for a preventive primary care visit since
      they had first had sex. This suggests that the preventive primary care visit is
      not being used to its full potential as an opportunity to screen and treat
      adolescents for sexually transmitted diseases. Capitalizing on this opportunity
      to screen may increase the number of cases of sexually transmitted diseases
      diagnosed and, thus, decrease rates of these diseases in this population.

PMID- 10924433
TI  - The race of patients and physicians can affect the quality of health care
      provision.

PMID- 10924434
TI  - A book that changed Me

PMID- 10924435
TI  - In patients with acute bronchitis, do antibiotics reduce sputum production,
      cough, or number of days off work?

PMID- 10924436
TI  - Does attendance at a general practice asthma clinic reduce asthma morbidity more
      than does standard medical treatment?

PMID- 10924437
TI  - Hope in the terminally ill.

PMID- 10924439
TI  - Babies and cream cheese

PMID- 10924438
TI  - From the cell to the community: AIDS research in California. The University of
      California Universitywide AIDS Research Program annual meeting, February 2000.

PMID- 10924440
TI  - Infections diseases: meningococcal disease.

PMID- 10924441
TI  - Does recreational ecstasy use cause long-term cognitive problems?

PMID- 10924442
TI  - Ectopic pregnancy.

PMID- 10924443
TI  - Dental injuries due to African traditional therapies for diarrhea.

PMID- 10924444
TI  - Is teething associated with diarrhea?

PMID- 10924446
TI  - A little conversation: reflections of a hospital volunteer

PMID- 10924447
TI  - The truth about proof.

PMID- 10924445
TI  - Heparin should be administered to every patient admitted to the hospital with
      possible unstable angina.

PMID- 10924448
TI  - Television promotes unsafe behaviors

PMID- 10924449
TI  - Subjectivity can be inhumane.

PMID- 10924450
TI  - The breast-feeding dilemma.

PMID- 10924451
TI  - Wolfgang Beermann (1921-2000): the man and his science.

PMID- 10924452
TI  - Double-strand break repair in tandem repeats during bacteriophage T4 infection.
AB  - Recombinational repair of double-strand breaks in tandemly repeated sequences
      often results in the loss of one or more copies of the repeat. The single-strand
      annealing (SSA) model for repair has been proposed to account for this
      nonconservative recombination. In this study we present a plasmid-based physical
      assay that measures SSA during bacteriophage T4 infection and apply this assay to
      the genetic analysis of break repair. SSA occurs readily in broken plasmid DNA
      and is independent of the strand exchange protein UvsX and its accessory factor
      UvsY. We use the unique features of T4 DNA metabolism to examine the link between
      SSA repair and DNA replication and demonstrate directly that the DNA polymerase
      and the major replicative helicase of the phage are not required for SSA repair.
      We also show that the Escherichia coli RecBCD enzyme can mediate the degradation
      of broken DNA during early, but not late, times of infection. Finally, we
      consider the status of broken ends during the course of the infection and propose
      a model for SSA during T4 infections.

PMID- 10924453
TI  - Natural selection, infectious transfer and the existence conditions for bacterial
      plasmids.
AB  - Despite the near-ubiquity of plasmids in bacterial populations and the profound
      contribution of infectious gene transfer to the adaptation and evolution of
      bacteria, the mechanisms responsible for the maintenance of plasmids in bacterial
      populations are poorly understood. In this article, we address the question of
      how plasmids manage to persist over evolutionary time. Empirical studies suggest
      that plasmids are not infectiously transmitted at a rate high enough to be
      maintained as genetic parasites. In part i, we present a general mathematical
      proof that if this is the case, then plasmids will not be able to persist
      indefinitely solely by carrying genes that are beneficial or sometimes beneficial
      to their host bacteria. Instead, such genes should, in the long run, be
      incorporated into the bacterial chromosome. If the mobility of host-adaptive
      genes imposes a cost, that mobility will eventually be lost. In part ii, we
      illustrate a pair of mechanisms by which plasmids can be maintained indefinitely
      even when their rates of transmission are too low for them to be genetic
      parasites. First, plasmids may persist because they can transfer locally adapted
      genes to newly arriving strains bearing evolutionary innovations, and thereby
      preserve the local adaptations in the face of background selective sweeps.
      Second, plasmids may persist because of their ability to shuttle intermittently
      favored genes back and forth between various (noncompeting) bacterial strains,
      ecotypes, or even species.

PMID- 10924454
TI  - A new genetic method for isolating functionally interacting genes: high plo1(+)
      dependent mutants and their suppressors define genes in mitotic and septation
      pathways in fission yeast.
AB  - We describe a general genetic method to identify genes encoding proteins that
      functionally interact with and/or are good candidates for downstream targets of a
      particular gene product. The screen identifies mutants whose growth depends on
      high levels of expression of that gene. We apply this to the plo1(+) gene that
      encodes a fission yeast homologue of the polo-like kinases. plo1(+) regulates
      both spindle formation and septation. We have isolated 17 high plo1(+)-dependent
      (pld) mutants that show defects in mitosis or septation. Three mutants show a
      mitotic arrest phenotype. Among the 14 pld mutants with septation defects, 12
      mapped to known loci: cdc7, cdc15, cdc11 spg1, and sid2. One of the pld mutants,
      cdc7-PD1, was selected for suppressor analysis. As multicopy suppressors, we
      isolated four known genes involved in septation in fission yeast: spg1(+),
      sce3(+), cdc8(+), and rho1(+), and two previously uncharacterized genes, mpd1(+)
      and mpd2(+). mpd1(+) exhibits high homology to phosphatidylinositol 4-phosphate 5
      kinase, while mpd2(+) resembles Saccharomyces cerevisiae SMY2; both proteins are
      involved in the regulation of actin-mediated processes. As chromosomal
      suppressors of cdc7-PD1, we isolated mutations of cdc16 that resulted in
      multiseptation without nuclear division. cdc16(+), dma1(+), byr3(+), byr4(+) and
      a truncated form of the cdc7 gene were isolated by complementation of one of
      these cdc16 mutations. These results demonstrate that screening for high dose
      dependent mutants and their suppressors is an effective approach to identify
      functionally interacting genes.

PMID- 10924455
TI  - Genetic analysis of the role of Pol II holoenzyme components in repression by the
      Cyc8-Tup1 corepressor in yeast.
AB  - The Cyc8-Tup1 corepressor complex is targeted to promoters by pathway-specific
      DNA-binding repressors, thereby inhibiting the transcription of specific classes
      of genes. Genetic screens have identified mutations in a variety of Pol II
      holoenzyme components (Srb8, Srb9, Srb10, Srb11, Sin4, Rgr1, Rox3, and Hrs1) and
      in the N-terminal tails of histones H3 and H4 that weaken repression by Cyc8
      Tup1. Here, we analyze the effect of individual and multiple mutations in many of
      these components on transcriptional repression of natural promoters that are
      regulated by Cyc8-Tup1. In all cases tested, individual mutations have a very
      modest effect on SUC2 RNA levels and no detectable effect on levels of ANB1,
      MFA2, and RNR2. Furthermore, multiple mutations within the Srb components,
      between Srbs and Sin4, and between Srbs and histone tails affect Cyc8-Tup1
      repression to the same modest extent as the individual mutations. These results
      argue that the weak effects of the various mutations on repression by Cyc8-Tup1
      are not due to redundancy among components of the Pol II machinery, and they
      argue against a simple redundancy between the holoenzyme and chromatin pathways.
      In addition, phenotypic analysis indicates that, although Srbs8-11 are
      indistinguishable with respect to Cyc8-Tup1 repression, the individual Srbs are
      functionally distinct in other respects. Genetic interactions among srb mutations
      imply that a balance between the activities of Srb8 + Srb10 and Srb11 is
      important for normal cell growth.

PMID- 10924456
TI  - Functional interaction between the PKC1 pathway and CDC31 network of SPB
      duplication genes.
AB  - The earliest known step in yeast spindle pole body (SPB) duplication requires
      Cdc31p and Kar1p, two physically interacting SPB components, and Dsk2p and
      Rad23p, a pair of ubiquitin-like proteins. Components of the PKC1 pathway were
      found to interact with these SPB duplication genes in two independent genetic
      screens. Initially, SLG1 and PKC1 were obtained as high-copy suppressors of
      dsk2Delta rad23Delta and a mutation in MPK1 was synthetically lethal with kar1
      Delta17. Subsequently, we demonstrated extensive genetic interactions between the
      PKC1 pathway and the SPB duplication mutants that affect Cdc31p function. The
      genetic interactions are unlikely to be related to the cell-wall integrity
      function of the PKC1 pathway because the SPB mutants did not exhibit cell-wall
      defects. Overexpression of multiple PKC1 pathway components suppressed the G2/M
      arrest of the SPB duplication mutants and mutations in MPK1 exacerbated the cell
      cycle arrest of kar1-Delta17, suggesting a role for the PKC1 pathway in SPB
      duplication. We also found that mutations in SPC110, which encodes a major SPB
      component, showed genetic interactions with both CDC31 and the PKC1 pathway. In
      support of the model that the PKC1 pathway regulates SPB duplication, one of the
      phosphorylated forms of Spc110p was absent in pkc1 and mpk1Delta mutants.

PMID- 10924457
TI  - Structure-function analysis of yeast mRNA cap methyltransferase and high-copy
      suppression of conditional mutants by AdoMet synthase and the ubiquitin
      conjugating enzyme Cdc34p.
AB  - Here we present a genetic analysis of the yeast cap-methylating enzyme Abd1p. To
      identify individual amino acids required for Abd1p function, we introduced
      alanine mutations at 35 positions of the 436-amino acid yeast protein. Two new
      recessive lethal mutations, F256A and Y330A, were identified. Alleles F256L and
      Y256L were viable, suggesting that hydrophobic residues at these positions
      sufficed for Abd1p function. Conservative mutations of Asp-178 established that
      an acidic moiety is essential at this position (i.e. , D178E was viable whereas
      D178N was not). Phe-256, Tyr-330, and Asp-178 are conserved in all known cellular
      cap methyltransferases. We isolated temperature-sensitive abd1 alleles and found
      that abd1-ts cells display a rapid shut-off of protein synthesis upon shift to
      the restrictive temperature, without wholesale reduction in steady-state mRNA
      levels. These in vivo results are consistent with classical biochemical studies
      showing a requirement for the cap methyl group in cap-dependent translation. We
      explored the issue of how cap methylation might be regulated in vivo by
      conducting a genetic screen for high-copy suppressors of the ts growth defect of
      abd1 mutants. The identification of the yeast genes SAM2 and SAM1, which encode
      AdoMet synthase, as abd1 suppressors suggests that Abd1p function can be
      modulated by changes in the concentration of its substrate AdoMet. We also
      identified the ubiquitin conjugating enzyme Cdc34p as a high-copy abd1
      suppressor. We show that mutations of Cdc34p that affect its ubiquitin
      conjugation activity or its capacity to interact with the E3-SCF complex abrogate
      its abd1 suppressor function. Moreover, the growth defect of abd1 mutants is
      exacerbated by cdc34-2. These findings suggest a novel role for Cdc34p in gene
      expression and engender a model whereby cap methylation or cap utilization is
      negatively regulated by a factor that is degraded when Cdc34p is overexpressed.

PMID- 10924458
TI  - Checkpoint proteins influence telomeric silencing and length maintenance in
      budding yeast.
AB  - A complex network of surveillance mechanisms, called checkpoints, interrupts cell
      cycle progression when damage to the genome is detected or when cells fail to
      complete DNA replication, thus ensuring genetic integrity. In budding yeast,
      components of the DNA damage checkpoint regulatory network include the RAD9,
      RAD17, RAD24, MEC3, DDC1, RAD53, and MEC1 genes that are proposed to be involved
      in different aspects of DNA metabolism. We provide evidence that some DNA damage
      checkpoint components play a role in maintaining telomere integrity. In fact,
      rad53 mutants specifically enhance repression of telomere-proximal transcription
      via the Sir-mediated pathway, suggesting that Rad53 might be required for proper
      chromatin structure at telomeres. Moreover, Rad53, Mec1, Ddc1, and Rad17 are
      necessary for telomere length maintenance, since mutations in all of these genes
      cause a decrease in telomere size. The telomeric shortening in rad53 and mec1
      mutants is further enhanced in the absence of SIR genes, suggesting that
      Rad53/Mec1 and Sir proteins contribute to chromosome end protection by different
      pathways. The finding that telomere shortening, but not increased telomeric
      repression of gene expression in rad53 mutants, can be suppressed by increasing
      dNTP synthetic capacity in these strains suggests that transcriptional silencing
      and telomere integrity involve separable functions of Rad53.

PMID- 10924459
TI  - POB3 is required for both transcription and replication in the yeast
      Saccharomyces cerevisiae.
AB  - Spt16 and Pob3 form stable heterodimers in Saccharomyces cerevisiae, and
      homologous proteins have also been purified as complexes from diverse eukaryotes.
      This conserved factor has been implicated in both transcription and replication
      and may affect both by altering the characteristics of chromatin. Here we
      describe the isolation and properties of a set of pob3 mutants and confirm that
      they have defects in both replication and transcription. Mutation of POB3 caused
      the Spt(-) phenotype, spt16 and pob3 alleles displayed severe synthetic defects,
      and elevated levels of Pob3 suppressed some spt16 phenotypes. These results are
      consistent with previous reports that Spt16 and Pob3 act in a complex that
      modulates transcription. Additional genetic interactions were observed between
      pob3 mutations and the genes encoding several DNA replication factors, including
      POL1, CTF4, DNA2, and CHL12. pob3 alleles caused sensitivity to the
      ribonucleotide reductase inhibitor hydroxyurea, indicating a defect in a process
      requiring rapid dNTP synthesis. Mutation of the S phase checkpoint gene MEC1
      caused pob3 mutants to lose viability rapidly under restrictive conditions,
      revealing defects in a process monitored by Mec1. Direct examination of DNA
      contents by flow cytometry showed that S phase onset and progression were delayed
      when POB3 was mutated. We conclude that Pob3 is required for normal replication
      as well as for transcription.

PMID- 10924460
TI  - Recombination can partially substitute for SPO13 in regulating meiosis I in
      budding yeast.
AB  - Recombination and chromosome synapsis bring homologous chromosomes together,
      creating chiasmata that ensure accurate disjunction during reductional division.
      SPO13 is a key gene required for meiosis I (MI) reductional segregation, but
      dispensable for recombination, in Saccharomyces cerevisiae. Absence of SPO13
      leads to single-division meiosis where reductional segregation is largely
      eliminated, but other meiotic events occur relatively normally. This phenotype
      allows haploids to produce viable meiotic products. Spo13p is thought to act by
      delaying nuclear division until sister centromeres/chromatids undergo proper
      cohesion for segregation to the same pole at MI. In the present study, a search
      for new spo13-like mutations that allow haploid meiosis recovered only new spo13
      alleles. Unexpectedly, an unusual reduced-expression allele (spo13-23) was
      recovered that behaves similarly to a null mutant in haploids but to a wild-type
      allele in diploids, dependent on the presence of recombining homologs rather than
      on a diploid genome. This finding demonstrates that in addition to promoting
      accurate homolog disjunction, recombination can also function to partially
      substitute for SPO13 in promoting sister cohesion. Analysis of various
      recombination-defective mutants indicates that this contribution of recombination
      to reductional segregation requires full levels of crossing over. The
      implications of these results regarding SPO13 function are discussed.

PMID- 10924461
TI  - A DNA polymerase epsilon mutant that specifically causes +1 frameshift mutations
      within homonucleotide runs in yeast.
AB  - The DNA polymerases delta and epsilon are the major replicative polymerases in
      the yeast Saccharomyces cerevisiae that possess 3' --> 5' exonuclease
      proofreading activity. Many errors arising during replication are corrected by
      these exonuclease activities. We have investigated the contributions of regions
      of Polepsilon other than the proofreading motifs to replication accuracy. An
      allele, pol2-C1089Y, was identified in a screen of Polepsilon mutants that in
      combination with an exonuclease I (exo1) mutation could cause a synergistic
      increase in mutations within homonucleotide runs. In contrast to other polymerase
      mutators, this allele specifically results in insertion frameshifts. When pol2
      C1089Y was combined with deletions of EXO1 or RAD27 (homologue of human FEN1),
      mutation rates were increased for +1 frameshifts while there was almost no effect
      on -1 frameshifts. On the basis of genetic analysis, the pol2-C1089Y mutation did
      not cause a defect in proofreading. In combination with a deletion of the
      mismatch repair gene MSH2, the +1 frameshift mutation rate for a short
      homonucleotide run was increased nearly 100-fold whereas the -1 frameshift rate
      was unchanged. This suggests that the Pol2-C1089Y protein makes +1 frameshift
      errors during replication of homonucleotide runs and that these errors can be
      corrected by either mismatch repair (MMR) or proofreading (in short runs). This
      is the first report of a +1-specific mutator for homonucleotide runs in vivo. The
      pol2-C1089Y mutation defines a functionally important residue in Polepsilon.

PMID- 10924462
TI  - The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two
      error-free postreplication repair pathways.
AB  - The RAD6 postreplication repair and mutagenesis pathway is the only major
      radiation repair pathway yet to be extensively characterized. It has been
      previously speculated that the RAD6 pathway consists of two parallel subpathways,
      one error free and another error prone (mutagenic). Here we show that the RAD6
      group genes can be exclusively divided into three rather than two independent
      subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is
      largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed error free.
      Mutants carrying characteristic mutations in each of the three subpathways are
      phenotypically indistinguishable from a single mutant such as rad18, which is
      defective in the entire RAD6 postreplication repair/tolerance pathway.
      Furthermore, the rad18 mutation is epistatic to all single or combined mutations
      in any of the above three subpathways. Our data also suggest that MMS2 and UBC13
      play a key role in coordinating the response of the error-free subpathways; Mms2
      and Ubc13 form a complex required for a novel polyubiquitin chain assembly, which
      probably serves as a signal transducer to promote both RAD5 and POL30 error-free
      postreplication repair pathways. The model established by this study will
      facilitate further research into the molecular mechanisms of postreplication
      repair and translesion DNA synthesis. In view of the high degree of sequence
      conservation of the RAD6 pathway genes among all eukaryotes, the model presented
      in this study may also apply to mammalian cells and predicts links to human
      diseases.

PMID- 10924464
TI  - The impact of lagging strand replication mutations on the stability of CAG repeat
      tracts in yeast.
AB  - We have examined the stability of long tracts of CAG repeats in yeast mutants
      defective in enzymes suspected to be involved in lagging strand replication.
      Alleles of DNA ligase (cdc9-1 and cdc9-2) destabilize CAG tracts in the stable
      tract orientation, i.e., when CAG serves as the lagging strand template. In this
      orientation nearly two-thirds of the events recorded in the cdc9-1 mutant were
      tract expansions. While neither DNA ligase allele significantly increases the
      frequency of tract-length changes in the unstable orientation, the cdc9-1 mutant
      produced a significant number of expansions in tracts of this orientation. A
      mutation in primase (pri2-1) destabilizes tracts in both the stable and the
      unstable orientations. Mutations in a DNA helicase/deoxyribonuclease (dna2-1) or
      in two RNase H activities (rnh1Delta and rnh35Delta) do not have a significant
      effect on CAG repeat tract stability. We interpret our results in terms of the
      steps of replication that are likely to lead to expansion and to contraction of
      CAG repeat tracts.

PMID- 10924463
TI  - Identification of domains required for developmentally regulated SNARE function
      in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae cells contain two homologues of the mammalian t-SNARE
      protein SNAP-25, encoded by the SEC9 and SPO20 genes. Although both gene products
      participate in post-Golgi vesicle fusion events, they cannot substitute for one
      another; Sec9p is active primarily in vegetative cells while Spo20p functions
      only during sporulation. We have investigated the basis for the developmental
      stage-specific differences in the function of these two proteins. Localization of
      the other plasma membrane SNARE subunits, Ssop and Sncp, in sporulating cells
      suggests that these proteins act in conjunction with Spo20p in the formation of
      the prospore membrane. In vitro binding studies demonstrate that, like Sec9p,
      Spo20p binds specifically to the t-SNARE Sso1p and, once bound to Sso1p, can
      complex with the v-SNARE Snc2p. Therefore, Sec9p and Spo20p interact with the
      same binding partners, but developmental conditions appear to favor the assembly
      of complexes with Spo20p in sporulating cells. Analysis of chimeric Sec9p/Spo20p
      molecules indicates that regions in both the SNAP-25 domain and the unique N
      terminus of Spo20p are required for activity during sporulation. Additionally,
      the N terminus of Spo20p is inhibitory in vegetative cells. Deletion studies
      indicate that activation and inhibition are separable functions of the Spo20p N
      terminus. Our results reveal an additional layer of regulation of the SNARE
      complex, which is necessary only in sporulating cells.

PMID- 10924465
TI  - Suppressors of a cold-sensitive mutation in yeast U4 RNA define five domains in
      the splicing factor Prp8 that influence spliceosome activation.
AB  - The highly conserved splicing factor Prp8 has been implicated in multiple stages
      of the splicing reaction. However, assignment of a specific function to any part
      of the 280-kD U5 snRNP protein has been difficult, in part because Prp8 lacks
      recognizable functional or structural motifs. We have used a large-scale screen
      for Saccharomyces cerevisiae PRP8 alleles that suppress the cold sensitivity
      caused by U4-cs1, a mutant U4 RNA that blocks U4/U6 unwinding, to identify with
      high resolution five distinct regions of PRP8 involved in the control of
      spliceosome activation. Genetic interactions between two of these regions reveal
      a potential long-range intramolecular fold. Identification of a yeast two-hybrid
      interaction, together with previously reported results, implicates two other
      regions in direct and indirect contacts to the U1 snRNP. In contrast to the
      suppressor mutations in PRP8, loss-of-function mutations in the genes for two
      other splicing factors implicated in U4/U6 unwinding, Prp44
      (Brr2/Rss1/Slt22/Snu246) and Prp24, show synthetic enhancement with U4-cs1. On
      the basis of these results we propose a model in which allosteric changes in Prp8
      initiate spliceosome activation by (1) disrupting contacts between the U1 snRNP
      and the U4/U6-U5 tri-snRNP and (2) orchestrating the activities of Prp44 and
      Prp24.

PMID- 10924466
TI  - Nonrandom spatial distribution of synonymous substitutions in the GP63 gene from
      Leishmania.
AB  - In this work we analyze the variability in substitution rates in the GP63 gene
      from Leishmania. By using a sliding window to estimate substitution rates along
      the gene, we found that the rate of synonymous substitutions along the GP63 gene
      is highly correlated with both the rate of amino acid substitution and codon
      bias. Furthermore, we show that comparisons involving genes that represent
      independent phylogenetic lines yield very similar divergence/conservation
      patterns, thus suggesting that deterministic forces (i.e., nonstochastic forces
      such as selection) generated these patterns. We present evidence indicating that
      the variability in substitution rates is unambiguously related to functionally
      relevant features. In particular, there is a clear relationship between rates and
      the tertiary structure of the encoded protein since all divergent segments are
      located on the surface of the molecule and facing one side (almost parallel to
      the cell membrane) on the exposed surface of the organism. Remarkably, the
      protein segments encoded by these variable regions encircle the active site in a
      funnel-like distribution. These results strongly suggest that the pattern of
      nucleotide divergence and, notably, of synonymous divergence is affected by
      functional constraints.

PMID- 10924467
TI  - Bacillus thuringiensis (Bt) toxin susceptibility and isolation of resistance
      mutants in the nematode Caenorhabditis elegans.
AB  - The protein toxins produced by Bacillus thuringiensis (Bt) are the most widely
      used natural insecticides in agriculture. Despite successful and extensive use of
      these toxins in transgenic crops, little is known about toxicity and resistance
      pathways in target insects since these organisms are not ideal for molecular
      genetic studies. To address this limitation and to investigate the potential use
      of these toxins to control parasitic nematodes, we are studying Bt toxin action
      and resistance in Caenorhabditis elegans. We demonstrate for the first time that
      a single Bt toxin can target a nematode. When fed Bt toxin, C. elegans
      hermaphrodites undergo extensive damage to the gut, a decrease in fertility, and
      death, consistent with toxin effects in insects. We have screened for and
      isolated 10 recessive mutants that resist the toxin's effects on the intestine,
      on fertility, and on viability. These mutants define five genes, indicating that
      more components are required for Bt toxicity than previously known. We find that
      a second, unrelated nematicidal Bt toxin may utilize a different toxicity
      pathway. Our data indicate that C. elegans can be used to undertake detailed
      molecular genetic analysis of Bt toxin pathways and that Bt toxins hold promise
      as nematicides.

PMID- 10924468
TI  - Evidence for selection at the fused locus of Drosophila virilis.
AB  - The genomic DNA sequence of a 2.4-kb region of the X-linked developmental gene
      fused was determined in 15 Drosophila virilis strains. One common replacement
      polymorphism is observed, where a negatively charged aspartic amino acid is
      replaced by the noncharged amino acid alanine. This replacement variant is
      located within the serine/threonine kinase domain of the fused gene and is
      present in approximately 50% of the sequences in our sample. Significant linkage
      disequilibrium is detected around this replacement site, although the fused gene
      is located in a region of the D. virilis X chromosome that seems to experience
      normal levels of recombination. In a 600-bp region around the replacement site,
      all eight alanine sequences are identical; of the six aspartic acid sequences,
      three are also identical. The occurrence of little or no variation within the
      aspartic acid and alanine haplotypes, coupled with the presence of several
      differences between them, is very unlikely under the usual equilibrium neutral
      model. Our results suggest that the fused alanine haplotypes have recently
      increased in frequency in the D. virilis population.

PMID- 10924469
TI  - The cryptocephal gene (ATF4) encodes multiple basic-leucine zipper proteins
      controlling molting and metamorphosis in Drosophila.
AB  - The cryptocephal (crc) mutation causes pleiotropic defects in ecdysone-regulated
      events during Drosophila molting and metamorphosis. Here we report that crc
      encodes a Drosophila homolog of vertebrate ATF4, a member of the CREB/ATF family
      of basic-leucine zipper (bZIP) transcription factors. We identified three
      putative protein isoforms. CRC-A and CRC-B contain the bZIP domain, and CRC-D is
      a C-terminally truncated form. We have generated seven new crc alleles.
      Consistent with the molecular diversity of crc, these alleles show that crc is a
      complex genetic locus with two overlapping lethal complementation groups. Alleles
      representing both groups were rescued by a cDNA encoding CRC-B. One lethal group
      (crc(1), crc(R6), and crc(Rev8)) consists of strong hypomorphic or null alleles
      that are associated with mutations of both CRC-A and CRC-B. These mutants display
      defects associated with larval molting and pupariation. In addition, they fail to
      evert the head and fail to elongate the imaginal discs during pupation, and they
      display variable defects in the subsequent differentiation of the adult abdomen.
      The other group (crc(R1), crc(R2), crc(E85), crc(E98), and crc(929)) is
      associated with disruptions of CRC-A and CRC-D; except for a failure to properly
      elongate the leg discs, these mutants initiate metamorphosis normally.
      Subsequently, they display a novel metamorphic phenotype, involving collapse of
      the head and abdomen toward the thorax. The crc gene is expressed throughout
      development and in many tissues. In third instar larvae, crc expression is high
      in targets of ecdysone signaling, such as the leg and wing imaginal discs, and in
      the ring gland, the source of ecdysone. Together, these findings implicate
      CREB/ATF proteins in essential functions during molting and metamorphosis. In
      addition, the similarities between the mutant phenotypes of crc and the ecdysone
      responsive genes indicate that these genes are likely to be involved in common
      signaling pathways.

PMID- 10924470
TI  - A screen for mutations that suppress the phenotype of Drosophila armadillo, the
      beta-catenin homolog.
AB  - During development signaling pathways coordinate cell fates and regulate the
      choice between cell survival or programmed cell death. The well-conserved
      Wingless/Wnt pathway is required for many developmental decisions in all animals.
      One transducer of the Wingless/Wnt signal is Armadillo/beta-catenin. Drosophila
      Armadillo not only transduces Wingless signal, but also acts in cell-cell
      adhesion via its role in the epithelial adherens junction. While many components
      of both the Wingless/Wnt signaling pathway and adherens junctions are known, both
      processes are complex, suggesting that unknown components influence signaling and
      junctions. We carried out a genetic modifier screen to identify some of these
      components by screening for mutations that can suppress the armadillo mutant
      phenotype. We identified 12 regions of the genome that have this property. From
      these regions and from additional candidate genes tested we identified four genes
      that suppress arm: dTCF, puckered, head involution defective (hid), and
      Dpresenilin. We further investigated the interaction with hid, a known regulator
      of programmed cell death. Our data suggest that Wg signaling modulates Hid
      activity and that Hid regulates programmed cell death in a dose-sensitive
      fashion.

PMID- 10924471
TI  - Sex determination in the Drosophila germline is dictated by the sexual identity
      of the surrounding soma.
AB  - It has been suggested that sexual identity in the germline depends upon the
      combination of a nonautonomous somatic signaling pathway and an autonomous X
      chromosome counting system. In the studies reported here, we have examined the
      role of the sexual differentiation genes transformer (tra) and doublesex (dsx) in
      regulating the activity of the somatic signaling pathway. We asked whether
      ectopic somatic expression of the female products of the tra and dsx genes could
      feminize the germline of XY animals. We find that Tra(F) is sufficient to
      feminize XY germ cells, shutting off the expression of male-specific markers and
      activating the expression of female-specific markers. Feminization of the
      germline depends upon the constitutively expressed transformer-2 (tra-2) gene,
      but does not seem to require a functional dsx gene. However, feminization of XY
      germ cells by Tra(F) can be blocked by the male form of the Dsx protein (Dsx(M)).
      Expression of the female form of dsx, Dsx(F), in XY animals also induced germline
      expression of female markers. Taken together with a previous analysis of the
      effects of mutations in tra, tra-2, and dsx on the feminization of XX germ cells
      in XX animals, our findings indicate that the somatic signaling pathway is
      redundant at the level tra and dsx. Finally, our studies call into question the
      idea that a cell-autonomous X chromosome counting system plays a central role in
      germline sex determination.

PMID- 10924473
TI  - Quantitative trait loci for life span in Drosophila melanogaster: interactions
      with genetic background and larval density.
AB  - The genetic architecture of variation in adult life span was examined for a
      population of recombinant inbred lines, each of which had been crossed to both
      inbred parental strains from which the lines were derived, after emergence from
      both high and low larval density. QTL affecting life span were mapped within each
      sex and larval density treatment by linkage to highly polymorphic roo
      transposable element markers, using a composite interval mapping method. We
      detected a total of six QTL affecting life span; the additive effects and degrees
      of dominance for all were highly sex- and larval environment-specific. There were
      significant epistatic interactions between five of the life span QTL, the effects
      of which also differed according to genetic background, sex, and larval density.
      Five additional QTL were identified that contributed to differences among lines
      in their sensitivity to variation in larval density. Further fine-scale mapping
      is necessary to determine whether candidate genes within the regions to which the
      QTL map are actually responsible for the observed variation in life span.

PMID- 10924472
TI  - Genetic studies of mei-P26 reveal a link between the processes that control germ
      cell proliferation in both sexes and those that control meiotic exchange in
      Drosophila.
AB  - We present the cloning and characterization of mei-P26, a novel P-element-induced
      exchange-defective female meiotic mutant in Drosophila melanogaster. Meiotic
      exchange in females homozygous for mei-P26(1) is reduced in a polar fashion, such
      that distal chromosomal regions are the most severely affected. Additional
      alleles generated by duplication of the P element reveal that mei-P26 is also
      necessary for germline differentiation in both females and males. To further
      assess the role of mei-P26 in germline differentiation, we tested double mutant
      combinations of mei-P26 and bag-of-marbles (bam), a gene necessary for the
      control of germline differentiation and proliferation in both sexes. A null
      mutation at the bam locus was found to act as a dominant enhancer of mei-P26 in
      both males and females. Interestingly, meiotic exchange in mei-P26(1);
      bam(Delta)(86)/+ females is also severely decreased in comparison to mei-P26(1)
      homozygotes, indicating that bam affects the meiotic phenotype as well. These
      data suggest that the pathways controlling germline differentiation and meiotic
      exchange are related and that factors involved in the mitotic divisions of the
      germline may regulate meiotic recombination.

PMID- 10924474
TI  - Function of RRM domains of Drosophila melanogaster ELAV: Rnp1 mutations and rrm
      domain replacements with ELAV family proteins and SXL.
AB  - Members of the ELAV family of proteins contain three RNA recognition motifs
      (RRMs), which are highly conserved. ELAV, a Drosophila melanogaster member of
      this family, provides a vital function and exhibits a predominantly nuclear
      localization. To investigate if the RNA-binding property of each of the ELAV RRMs
      is required for ELAV's in vivo function, amino acid residues critical in RNA
      binding for each RRM were individually mutated. A stringent genetic
      complementation test revealed that when the mutant protein was the sole source of
      ELAV, RNA-binding ability of each RRM was essential to ELAV function. To assess
      the degree to which each domain was specific for ELAV function and which domains
      perhaps performed a function common to related ELAV proteins, we substituted an
      ELAV RRM with the corresponding RRM from RBP9, the D. melanogaster protein most
      homologous to ELAV; HuD, a human ELAV family protein; and SXL, which, although
      evolutionarily related, is not an ELAV family member. This analysis revealed that
      RRM3 replacements were fully functional, but RRM1 and RRM2 replacements were
      largely nonfunctional. Under less stringent conditions RRM1 and RRM2 replacements
      from SXL and RRM1 replacement from RBP9 were able to provide supplemental
      function in the presence of a mutant hypomorphic ELAV protein.

PMID- 10924475
TI  - The Drosophila embargoed gene is required for larval progression and encodes the
      functional homolog of schizosaccharomyces Crm1.
AB  - The CRM1 (Exportin 1) protein is a receptor for leucine-rich nuclear export
      signal sequences. We have molecularly characterized the Drosophila melanogaster
      embargoed (emb) gene and find that it encodes a product with 49 and 71% sequence
      identity to the fission yeast Schizosaccharomyces pombe and human CRM1 proteins,
      respectively. We show that expression of the emb cDNA is sufficient to suppress
      the growth phenotype of both conditional-lethal and null S. pombe crm1(-) mutant
      strains, suggesting that emb encodes the functional homologue of the S. pombe
      Crm1 protein. Through mutagenesis screens we have recovered a series of recessive
      lethal emb mutations. There is a substantial maternal contribution of emb mRNA
      and animals hemizygous for our emb alleles can develop to second instar larvae
      but persist at this stage and consistently fail to undergo the molt to the third
      instar stage. We see a nuclear accumulation of endogenous actin in the intestinal
      epithelial cells of the emb mutant larvae, consistent with a role for the emb
      gene product in nuclear export of actin protein.

PMID- 10924476
TI  - The Drosophila cystoblast differentiation factor, benign gonial cell neoplasm, is
      related to DExH-box proteins and interacts genetically with bag-of-marbles.
AB  - Selection of asymmetric cell fates can involve both intrinsic and extrinsic
      factors. Previously we have identified the bag-of-marbles (bam) gene as an
      intrinsic factor for cystoblast fate in Drosophila germline cells and shown that
      it requires active product from the benign gonial cell neoplasm (bgcn) gene. Here
      we present the cloning and characterization of bgcn. The predicted Bgcn protein
      is related to the DExH-box family of RNA-dependent helicases but lacks critical
      residues for ATPase and helicase functions. Expression of the bgcn gene is
      extremely limited in ovaries but, significantly, bgcn mRNA is expressed in a very
      limited number of germline cells, including the stem cells. Also, mutations in
      bgcn dominantly enhance a bam mutant phenotype, further corroborating the
      interdependence of these two genes' functions. On the basis of known functions of
      DExH-box proteins, we propose that Bgcn and Bam may be involved in regulating
      translational events that are necessary for activation of the cystoblast
      differentiation program.

PMID- 10924477
TI  - Distinct P-element excision products in somatic and germline cells of Drosophila
      melanogaster.
AB  - The footprints remaining following somatic P-element excision from the Drosophila
      white locus were recovered and characterized. Two different types of footprints
      were observed. Over 75% of the footprints were short, composed of 4 or 7
      nucleotides of the P-element inverted terminal repeat, and were similar to those
      found in a previously described plasmid excision assay. The remaining footprints
      were composed of 14-18 nucleotides of both inverted terminal repeats. These large
      footprints were indistinguishable from those recovered following germline P
      element excision. Enhanced expression of the Drosophila homologue of the Ku70
      protein did not affect the structure of the somatic footprints. Therefore, this
      protein is not a limiting factor for double-strand break repair by nonhomologous
      end-joining in Drosophila somatic cells.

PMID- 10924478
TI  - The only function of Grauzone required for Drosophila oocyte meiosis is
      transcriptional activation of the cortex gene.
AB  - The grauzone and cortex genes are required for the completion of meiosis in
      Drosophila oocytes. The grauzone gene encodes a C2H2-type zinc-finger
      transcription factor that binds to the cortex promoter and is necessary for high
      level activation of cortex transcription. Here we define the region of the cortex
      promoter to which Grauzone binds and show that the binding occurs through the C
      terminal, zinc-finger-rich region of the protein. Mutations in two out of the
      five grauzone alleles result in single amino acid changes within different zinc
      finger motifs. Both of these mutations result in the inability of Grauzone to
      bind DNA effectively. To determine the mechanism by which Grauzone regulates
      meiosis, transgenic flies were produced with an extra copy of the cortex gene in
      homozygous grauzone females. This transgene rescued the meiosis arrest of embryos
      from these mutants and allowed their complete development, indicating that
      activation of cortex transcription is the primary role of Grauzone during
      Drosophila oogenesis. These experiments further define a new transcriptional
      pathway that controls the meiotic cell cycle in Drosophila oocytes.

PMID- 10924479
TI  - P-Element repression in Drosophila melanogaster by a naturally occurring
      defective telomeric P copy.
AB  - In Drosophila melanogaster, hybrid dysgenesis occurs in progeny from crosses
      between females lacking P elements and males carrying P elements scattered
      throughout the genome. We have genetically isolated a naturally occurring P
      insertion at cytological location 1A, from a Tunisian population. The Nasr'Allah
      P(1A) element [NA-P(1A)] has a deletion of the first 871 bp including the P
      promoter. It is flanked at the 3' end by telomeric associated sequences and at
      the 5' end by a HeT-A element sequence. The NA-P(1A) element strongly represses
      dysgenic sterility and P transposition. However, when testing P-promoter
      repression, NA-P(1A) was unable to repress a germinally expressed P-lacZ
      construct bearing no 5'-homology with it. Conversely, a second P-lacZ construct,
      in which the fusion with lacZ takes place in exon 3 of P, was successfully
      repressed by NA-P(1A). This suggests that NA-P(1A) repression involves a homology
      dependent component.

PMID- 10924480
TI  - Contrasting evolutionary histories of two introns of the duchenne muscular
      dystrophy gene, Dmd, in humans.
AB  - The Duchenne muscular dystrophy (Dmd) locus lies in a region of the X chromosome
      that experiences a high rate of recombination and is thus expected to be
      relatively unaffected by the effects of selection on nearby genes. To provide a
      picture of nucleotide variability at a high-recombination locus in humans, we
      sequenced 5. 4 kb from two introns of Dmd in a worldwide sample of 41 alleles
      from Africa, Asia, Europe, and the Americas. These same regions were also
      sequenced in one common chimpanzee and one orangutan. Dramatically different
      patterns of genetic variation were observed at these two introns, which are
      separated by >500 kb of DNA. Nucleotide diversity at intron 44 pi = 0.141% was
      more than four times higher than nucleotide diversity at intron 7 pi = 0.034%
      despite similar levels of divergence for these two regions. Intron 7 exhibited
      significant linkage disequilibrium extending over 10 kb and also showed a
      significant excess of rare polymorphisms. In contrast, intron 44 exhibited little
      linkage disequilibrium and no skew in the frequency distribution of segregating
      sites. Intron 7 was much more variable in Africa than in other continents, while
      intron 44 displayed similar levels of variability in different geographic
      regions. Comparison of intraspecific polymorphism to interspecific divergence
      using the HKA test revealed a significant reduction in variability at intron 7
      relative to intron 44, and this effect was most pronounced in the non-African
      samples. These results are best explained by positive directional selection
      acting at or near intron 7 and demonstrate that even genes in regions of high
      recombination may be influenced by selection at linked sites.

PMID- 10924482
TI  - The maternal chromosome set is the target of the T-DNA in the in planta
      transformation of Arabidopsis thaliana.
AB  - In planta transformation methods are now commonly used to transform Arabidopsis
      thaliana by Agrobacterium tumefaciens. The origin of transformants obtained by
      these methods has been studied by inoculating different floral stages and
      examining gametophytic expression of an introduced beta-glucuronidase marker gene
      encoding GUS. We observed that transformation can still occur after treating
      flowers where embryo sacs have reached the stage of the third division. No GUS
      expression was observed in embryo sacs or pollen of plants infiltrated with an
      Agrobacterium strain bearing a GUS gene under the control of a gametophyte
      specific promoter. To identify the genetic target we used an insertion mutant in
      which a gene essential for male gametophytic development has been disrupted by a
      T-DNA bearing a Basta resistance gene (B(R)). In this mutant the B(R) marker is
      transferred to the progeny only by the female gametes. This mutant was
      retransformed with a hygromycin resistance marker and doubly resistant plants
      were selected. The study of 193 progeny of these transformants revealed 25 plants
      in which the two resistance markers were linked in coupling and only one plant
      where they were linked in repulsion. These results point to the chromosome set of
      the female gametophyte as the main target for the T-DNA.

PMID- 10924481
TI  - When did the human population size start increasing?
AB  - We analyze the frequency spectra of all available human nuclear sequence data
      sets by using a model of constant population size followed by exponential growth.
      Parameters of growth (more extreme than or) comparable to what has been suggested
      from mtDNA data can be rejected for 6 out of the 10 largest data sets. When the
      data are separated into African and non-African samples, a constant size no
      growth model can be rejected for 4 out of 8 non-African samples. Long-term growth
      (i.e., starting 50-100 kya) can be rejected for 2 out of 8 African samples and 5
      out of 8 non-African ones. Under more complex demographic models, including a
      bottleneck or population subdivision, more of the data are compatible with long
      term growth. One problem with the data used here is that a subset of loci may
      reflect the action of natural selection as well as of demography. It remains
      possible that the correct demographic model is one of constant population size
      followed by long-term growth but that at several loci the demographic signature
      has been obscured by balancing or diversifying selection. However, it is not
      clear that the data at these loci are consistent with a simple model of balancing
      selection; more complicated selective alternatives cannot be tested unless they
      are made explicit. An alternative explanation is that population size growth is
      more recent (e.g., upper Paleolithic) and that some of the loci have experienced
      recent directional selection. Given the available data, the latter hypothesis
      seems more likely.

PMID- 10924483
TI  - Developmental patterns of chromatin structure and DNA methylation responsible for
      epigenetic expression of a maize regulatory gene.
AB  - Epigenetic regulatory mechanisms heritably alter patterns of gene expression
      without changes in DNA sequence. Epigenetic states are often correlated with
      developmentally imposed alterations in genomic DNA methylation and local
      chromatin structure. Pl-Blotched is a stable epigenetic allele of the maize
      anthocyanin regulatory gene, purple plant1(pl). Pl-Blotched plants display a
      variegated pattern of pigmentation that contrasts sharply with the uniformly dark
      purple pigmentation of plants carrying the dominant Pl-Rhoades allele.
      Previously, we showed that the lower level of pigmentation in Pl-Blotched is
      correlated with lower pl mRNA levels and increased DNA methylation at some sites.
      To explore how DNA methylation, chromatin structure, and developmental stage
      might contribute to the expression of Pl-Blotched, we used methylation-sensitive
      restriction enzymes and DNaseI sensitivity assays to compare the methylation
      status and chromatin structure of Pl-Blotched and Pl-Rhoades at different stages
      in development. Both alleles exhibit developmentally sensitive changes in
      methylation. In Pl-Blotched, methylation of two diagnostic HpaII/MspI sites
      increases progressively, coincident with the juvenile-to-adult transition in
      growth. In seedlings, the chromatin encompassing the coding region of the gene is
      less sensitive to DNaseI digestion in Pl-Blotched than in Pl-Rhoades.
      Developmental maturation from seedling to adult is accompanied by expansion of
      this closed chromatin domain to include the promoter and downstream flanking
      sequences. We provide evidence to show that chromatin structure, rather than DNA
      methylation, is the primary epigenetic determinant for the phenotypic differences
      between Pl-Blotched and Pl-Rhoades.

PMID- 10924484
TI  - Molecular evolution of the avian CHD1 genes on the Z and W sex chromosomes.
AB  - Genes shared between the nonrecombining parts of the two types of sex chromosomes
      offer a potential means to study the molecular evolution of the same gene exposed
      to different genomic environments. We have analyzed the molecular evolution of
      the coding sequence of the first pair of genes found to be shared by the avian Z
      (present in both sexes) and W (female-specific) sex chromosomes, CHD1Z and CHD1W.
      We show here that these two genes evolve independently but are highly conserved
      at nucleotide as well as amino acid levels, thus not indicating a female-specific
      role of the CHD1W gene. From comparisons of sequence data from three avian
      lineages, the frequency of nonsynonymous substitutions (K(a)) was found to be
      higher for CHD1W (1.55 per 100 sites) than for CHD1Z (0.81), while the opposite
      was found for synonymous substitutions (K(s), 13.5 vs. 22.7). We argue that the
      lower effective population size and the absence of recombination on the W
      chromosome will generally imply that nonsynonymous substitutions accumulate
      faster on this chromosome than on the Z chromosome. The same should be true for
      the Y chromosome relative to the X chromosome in XY systems. Our data are
      compatible with a male-biased mutation rate, manifested by the faster rate of
      neutral evolution (synonymous substitutions) on the Z chromosome than on the
      female-specific W chromosome.

PMID- 10924485
TI  - Copy number lability and evolutionary dynamics of the Adh gene family in diploid
      and tetraploid cotton (Gossypium).
AB  - Nuclear-encoded genes exist in families of various sizes. To further our
      understanding of the evolutionary dynamics of nuclear gene families we present a
      characterization of the structure and evolution of the alcohol dehydrogenase
      (Adh) gene family in diploid and tetraploid members of the cotton genus
      (Gossypium, Malvaceae). A PCR-based approach was employed to isolate and sequence
      multiple Adh gene family members, and Southern hybridization analyses were used
      to document variation in gene copy number. Adh gene copy number varies among
      Gossypium species, with diploids containing at least seven Adh loci in two
      primary gene lineages. Allotetraploid Gossypium species are inferred to contain
      at least 14 loci. Intron lengths vary markedly between loci, and one locus has
      lost two introns usually found in other plant Adh genes. Multiple examples of
      apparent gene duplication events were observed and at least one case of
      pseudogenization and one case of gene elimination were also found. Thus, Adh gene
      family structure is dynamic within this single plant genus. Evolutionary rate
      estimates differ between loci and in some cases between organismal lineages at
      the same locus. We suggest that dynamic fluctuation in copy number will prove
      common for nuclear genes, and we discuss the implications of this perspective for
      inferences of orthology and functional evolution.

PMID- 10924487
TI  - The relationship between count-location and stationary renewal models for the
      chiasma process.
AB  - It is often convenient to define models for the process of chiasma formation at
      meiosis as stationary renewal models. However, count-location models are also
      useful, particularly to capture the biological requirement of at least one
      chiasma per chromosome. The Sturt model and truncated Poisson model are both
      count-location models with this feature. We show that the truncated Poisson model
      can also be expressed as a stationary renewal model, while the Sturt model
      cannot. More generally, we show that there is only one family of count-location
      models for the chiasma process that can also be expressed as stationary renewal
      models. The models in this family can exhibit either positive or negative
      interference.

PMID- 10924486
TI  - Comparative mapping of quantitative trait loci sculpting the curd of Brassica
      oleracea.
AB  - The enlarged inflorescence (curd) of cauliflower and broccoli provide not only a
      popular vegetable for human consumption, but also a unique opportunity for
      scientists who seek to understand the genetic basis of plant growth and
      development. By the comparison of quantitative trait loci (QTL) maps constructed
      from three different F(2) populations, we identified a total of 86 QTL that
      control eight curd-related traits in Brassica oleracea. The 86 QTL may reflect
      allelic variation in as few as 67 different genetic loci and 54 ancestral genes.
      Although the locations of QTL affecting a trait occasionally corresponded between
      different populations or between different homeologous Brassica chromosomes, our
      data supported other molecular and morphological data in suggesting that the
      Brassica genus is rapidly evolving. Comparative data enabled us to identify a
      number of candidate genes from Arabidopsis that warrant further investigation to
      determine if some of them might account for Brassica QTL. The
      Arabidopsis/Brassica system is an important example of both the challenges and
      opportunities associated with extrapolation of genomic information from facile
      models to large-genome taxa including major crops.

PMID- 10924488
TI  - Estimating quantitative genetic parameters using sibships reconstructed from
      marker data.
AB  - Previous techniques for estimating quantitative genetic parameters, such as
      heritability in populations where exact relationships are unknown but are instead
      inferred from marker genotypes, have used data from individuals on a pairwise
      level only. At this level, families are weighted according to the number of pairs
      within which each family appears, hence by size rather than information content,
      and information from multiple relationships is lost. Estimates of parameters are
      therefore not the most efficient achievable. Here, Markov chain Monte Carlo
      techniques have been used to partition the population into complete sibships,
      including, if known, prior knowledge of the distribution of family sizes. These
      pedigrees have then been used with restricted maximum likelihood under an animal
      model to estimate quantitative genetic parameters. Simulations to compare the
      properties of parameter estimates with those of existing techniques indicate that
      the use of sibship reconstruction is superior to earlier methods, having lower
      mean square errors and showing nonsignificant downward bias. In addition, sibship
      reconstruction allows the estimation of population allele frequencies that
      account for the relationships within the sample, so prior knowledge of allele
      frequencies need not be assumed. Extensions to these techniques allow
      reconstruction of half sibships when some or all of the maternal genotypes are
      known.

PMID- 10924489
TI  - Conditional genotypic probabilities for microsatellite loci.
AB  - Modern forensic DNA profiles are constructed using microsatellites, short tandem
      repeats of 2-5 bases. In the absence of genetic data on a crime-specific
      subpopulation, one tool for evaluating profile evidence is the match probability.
      The match probability is the conditional probability that a random person would
      have the profile of interest given that the suspect has it and that these people
      are different members of the same subpopulation. One issue in evaluating the
      match probability is population differentiation, which can induce coancestry
      among subpopulation members. Forensic assessments that ignore coancestry
      typically overstate the strength of evidence against the suspect. Theory has been
      developed to account for coancestry; assumptions include a steady-state
      population and a mutation model in which the allelic state after a mutation event
      is independent of the prior state. Under these assumptions, the joint allelic
      probabilities within a subpopulation may be approximated by the moments of a
      Dirichlet distribution. We investigate the adequacy of this approximation for
      profiled loci that mutate according to a generalized stepwise model. Simulations
      suggest that the Dirichlet theory can still overstate the evidence against a
      suspect with a common microsatellite genotype. However, Dirichlet-based
      estimators were less biased than the product-rule estimator, which ignores
      coancestry.

PMID- 10924490
TI  - An inbreeding model of associative overdominance during a population bottleneck.
AB  - Associative overdominance, the fitness difference between heterozygotes and
      homozygotes at a neutral locus, is classically described using two categories of
      models: linkage disequilibrium in small populations or identity disequilibrium in
      infinite, partially selfing populations. In both cases, only equilibrium
      situations have been considered. In the present study, associative overdominance
      is related to the distribution of individual inbreeding levels (i.e., genomic
      autozygosity). Our model integrates the effects of physical linkage and variation
      in inbreeding history among individual pedigrees. Hence, linkage and identity
      disequilibrium, traditionally presented as alternatives, are summarized within a
      single framework. This allows studying nonequilibrium situations in which both
      occur simultaneously. The model is applied to the case of an infinite population
      undergoing a sustained population bottleneck. The effects of bottleneck size,
      mating system, marker gene diversity, deleterious genomic mutation parameters,
      and physical linkage are evaluated. Bottlenecks transiently generate much larger
      associative overdominance than observed in equilibrium finite populations and
      represent a plausible explanation of empirical results obtained, for instance, in
      marine species. Moreover, the main origin of associative overdominance is random
      variation in individual inbreeding whereas physical linkage has little effect.

PMID- 10924491
TI  - On the average coefficient of dominance of deleterious spontaneous mutations.
AB  - T. Mukai and co-workers in the late 1960s and O. Ohnishi in the 1970s carried out
      a series of experiments to obtain direct estimates of the average coefficient of
      dominance (h) of minor viability mutations in Drosophila melanogaster. The
      results of these experiments, although inconsistent, have been interpreted as
      indicating slight recessivity of deleterious mutations, with h approximately 0.4.
      Mukai obtained conflicting results depending on the type of heterozygotes used,
      some estimates suggesting overdominance and others partial dominance. Ohnishi's
      estimates, based on the ratio of heterozygous to homozygous viability declines,
      were more consistent, pointing to the above value. However, we have reanalyzed
      Ohnishi's data, estimating h by the regression method, and obtained a much
      smaller estimate of approximately 0.1. This significant difference can be due
      partly to the different weighting implicit in the estimates, but we suggest that
      this is not the only explanation. We propose as a plausible hypothesis that a
      putative nonmutational decline in viability occurring in the first half of
      Ohnishi's experiment (affecting both homozygotes and heterozygotes) has biased
      upward the estimates from the ratio, while it would not bias the regression
      estimates. This hypothesis also explains the very high h approximately 0.7
      observed in Ohnishi's high-viability chromosomes. By constructing a model of
      spontaneous mutations using parameters in the literature, we investigate the
      above possibility. The results indicate that a model of few mutations with
      moderately large effects and h approximately 0.2 is able to explain the observed
      estimates and the distributions of homozygous and heterozygous viabilities.
      Accounting for an expression of mutations in genotypes with the balancer
      chromosome Cy does not alter the conclusions qualitatively.

PMID- 10924492
TI  - The use of a genetic algorithm for simultaneous mapping of multiple interacting
      quantitative trait loci.
AB  - Here we describe a general method for improving computational efficiency in
      simultaneous mapping of multiple interacting quantitative trait loci (QTL). The
      method uses a genetic algorithm to search for QTL in the genome instead of an
      exhaustive enumerative ("step-by-step") search. It can be used together with any
      method of QTL mapping based on a genomic search, since it only provides a more
      efficient way to search the genome for QTL. The computational demand decreases by
      a factor of approximately 130 when using genetic algorithm-based mapping instead
      of an exhaustive enumerative search for two QTL in a genome size of 2000 cM using
      a resolution of 1 cM. The advantage of using a genetic algorithm increases
      further for larger genomes, higher resolutions, and searches for more QTL. We
      show that a genetic algorithm-based search has efficiency higher than or equal to
      a search method conditioned on previously identified QTL for all epistatic models
      tested and that this efficiency is comparable to that of an exhaustive search for
      multiple QTL. The genetic algorithm is thus a powerful and computationally
      tractable alternative to the exhaustive enumerative search for simultaneous
      mapping of multiple interacting QTL. The use of genetic algorithms for
      simultaneous mapping of more than two QTL and for determining empirical
      significance thresholds using permutation tests is also discussed.

PMID- 10924494
TI  - Analysis of sir2p domains required for rDNA and telomeric silencing in
      saccharomyces cerevisiae

PMID- 10924493
TI  - A new statistic for detecting genetic differentiation.
AB  - A new statistic for detecting genetic differentiation of subpopulations is
      described. The statistic can be calculated when genetic data are collected on
      individuals sampled from two or more localities. It is assumed that haplotypic
      data are obtained, either in the form of DNA sequences or data on many tightly
      linked markers. Using a symmetric island model, and assuming an infinite-sites
      model of mutation, it is found that the new statistic is as powerful or more
      powerful than previously proposed statistics for a wide range of parameter
      values.

PMID- 10924495
TI  - The relationship between homology length and crossing over during the repair of a
      broken chromosome.
AB  - Homologous recombination can result in the transfer of genetic information from
      one DNA molecule to another (gene conversion). These events are often accompanied
      by a reciprocal exchange between the interacting molecules (termed "crossing
      over"). This association suggests that the two types of events could be
      mechanistically related. We have analyzed the repair, by homologous
      recombination, of a broken chromosome in yeast. We show that gene conversion can
      be uncoupled from crossing over when the length of homology of the interacting
      substrates is below a certain threshold. In addition, a minimal length of
      homology on each broken chromosomal arm is needed for crossing over. We also show
      that the coupling between gene conversion and crossing over is affected by the
      mismatch repair system; mutations in the MSH2 or MSH6 genes cause an increase in
      the crossing over observed for short alleles. Our results provide a mechanism to
      explain how chromosomal recombinational repair can take place without altering
      the stability of the genome.

PMID- 10924496
TI  - A novel glutathione containing eicosanoid (FOG7) chemotactic for human
      granulocytes.
AB  - A biologically active glutathione adduct of the eicosanoid 5-oxo-eicosatetraenoic
      acid has been observed as a product formed within the murine peritoneal
      macrophage. This five-oxo glutathione adduct (FOG(7)) was structurally
      characterized using electrospray tandem mass spectrometry as a 1,4 Michael
      addition product 5-oxo-7-glutathionyl-8,11,14-eicosatrienoic acid. FOG(7) was
      found to be highly potent in stimulating eosinophil as well as neutrophil
      chemotaxis, also capable of initiating actin polymerization, without elevating
      intracellular free calcium ion concentration within either the eosinophil or
      polymorphonuclear leukocyte. These biological responses suggest that either
      FOG(7) activates a subset of receptors mediating the broader biological activity
      of the parent eicosanoid 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) or
      that a receptor not activated by 5-oxo-ETE participates in the chemotactic
      activity of FOG(7). The only other known biologically active glutathione adduct
      has been leukotriene C(4) (LTC(4)), another eicosanoid that exerts potent effects
      through the Cys-LT receptor. The biochemical parallel between the formation of
      LTC(4) and FOG(7) suggests an interesting mechanism by which biologically active
      eicosanoids derived from electrophilic intermediates may have unique distribution
      and prolonged efficacy in vivo.

PMID- 10924497
TI  - Hepatitis C virus core protein enhances p53 function through augmentation of DNA
      binding affinity and transcriptional ability.
AB  - Hepatitis C virus (HCV) causes a persistent infection, chronic hepatitis, and
      hepatocellular carcinoma. Since there are several reports indicating that some
      viruses influence the tumor suppressor p53 function, we determined the effects of
      HCV proteins on p53 function and its mechanism determined by use of a reporter
      assay. Among seven HCV proteins investigated (core, NS2, NS3, NS4A, NS4B, NS5A,
      and NS5B), only core protein augmented the transcriptional activity of p53 and
      increased the expression of p21(waf1) protein, which is a major target of p53.
      Core protein increased both DNA-binding affinity of p53 in electrophoretic
      morbidity shift assay and transcriptional ability of p53 itself in a reporter
      assay. The direct interaction between core protein and C terminus of p53 was also
      shown by glutathione S-transferase fusion protein binding assay. In addition,
      core protein interacted with hTAF(II)28, a component of the transcriptional
      factor complex in vivo and in vitro. These results suggest that HCV core protein
      interacts with p53 and modulates p53-dependent promoter activities during HCV
      infection.

PMID- 10924498
TI  - Multiplicity, structures, and endocrine and exocrine natures of eel fucose
      binding lectins.
AB  - Lectins, a group of proteins that bind to cell surface carbohydrates and play
      important roles in innate immunity, are widely used experimentally to distinguish
      cell types and to induce cell proliferation. Eel serum lectins have been useful
      as anti-H hemagglutinins and also in lectin histochemistry as fucose-binding
      lectins (fucolectins), but their structures have not been determined. Here we
      report the primary structures and the sites of synthesis of eel fucolectins. Eel
      serum fucolectins were separated by two-dimensional gel electrophoresis and
      sequenced. cDNA cloning, based on the amino acid sequence information, and
      Northern blot analysis indicated that 1) the fucose-binding lectins are secretory
      proteins and have unique structures among the lectins, exhibiting only weak
      similarities to frog pentraxin, horseshoe crab tachylectin-4, and fly fw protein;
      2) there are at least seven closely related members; and 3) their messages are
      abundantly expressed in the liver and in significant levels in the gill and
      intestine. The lectin-producing hepatic cells were identified by immunostaining;
      in the gill, exocrine mucous cells were stained, suggesting that serum
      fucolectins derive from the liver. Using primary culture of eel hepatocytes, the
      message levels were shown to be increased by lipopolysaccharide, suggesting a
      role for fucolectins in host defense. SDS-polyacrylamide gel electrophoresis
      analysis showed that eel fucolectins have a SDS-resistant tetrameric structure
      consisting of two disulfide-linked dimers.

PMID- 10924499
TI  - A human homolog of angiotensin-converting enzyme. Cloning and functional
      expression as a captopril-insensitive carboxypeptidase.
AB  - A novel human zinc metalloprotease that has considerable homology to human
      angiotensin-converting enzyme (ACE) (40% identity and 61% similarity) has been
      identified. This metalloprotease (angiotensin-converting enzyme homolog (ACEH))
      contains a single HEXXH zinc-binding domain and conserves other critical residues
      typical of the ACE family. The predicted protein sequence consists of 805 amino
      acids, including a potential 17-amino acid N-terminal signal peptide sequence and
      a putative C-terminal membrane anchor. Expression in Chinese hamster ovary cells
      of a soluble, truncated form of ACEH, lacking the transmembrane and cytosolic
      domains, produces a glycoprotein of 120 kDa, which is able to cleave angiotensin
      I and angiotensin II but not bradykinin or Hip-His-Leu. In the hydrolysis of the
      angiotensins, ACEH functions exclusively as a carboxypeptidase. ACEH activity is
      inhibited by EDTA but not by classical ACE inhibitors such as captopril,
      lisinopril, or enalaprilat. Identification of the genomic sequence of ACEH has
      shown that the ACEH gene contains 18 exons, of which several have considerable
      size similarity with the first 17 exons of human ACE. The gene maps to
      chromosomal location Xp22. Northern blotting analysis has shown that the ACEH
      mRNA transcript is approximately 3. 4 kilobase pairs and is most highly expressed
      in testis, kidney, and heart. This is the first report of a mammalian homolog of
      ACE and has implications for our understanding of cardiovascular and renal
      function.

PMID- 10924500
TI  - Trimer carboxyl propeptide of collagen I produced by mature osteoblasts is
      chemotactic for endothelial cells.
AB  - During the second phase of osteogenesis in vitro, rat osteoblasts secrete
      inducer(s) of chemotaxis and chemoinvasion of endothelial and tumor cells. We
      report here the characterization and purification from mature osteoblast
      conditioned medium of the agent chemotactic for endothelial cells. The
      chemoactive conditioned medium specifically induces directional migration of
      endothelial cells, not affecting the expression and activation of gelatinases,
      cell proliferation, and scattering. Directional migration induced in endothelial
      cells by conditioned medium from osteoblasts is inhibited by pertussis toxin, by
      blocking antibodies to integrins alpha(1), beta(1), and beta(3), and by
      antibodies to metalloproteinase 2 and 9. The biologically active purified protein
      has two sequences, coincident with the amino-terminal amino acids, respectively,
      of the alpha(1) and of the alpha(2) carboxyl propeptides of type I collagen, as
      physiologically produced by procollagen C proteinase. Antibodies to type I
      collagen and to the carboxyl terminus of alpha(1) or alpha(2) chains inhibit
      chemotaxis. The chemoattractant is the propeptide trimer carboxyl-terminal to
      type I collagen, and its activity is lost upon reduction. These data illustrate a
      previously unknown function for the carboxyl-terminal trimer, possibly relevant
      in promoting endothelial cell migration and vascularization of tissues producing
      collagen type I.

PMID- 10924502
TI  - Identification of two transmembrane regions and a cytosolic domain of rat
      mitochondrial glycerophosphate acyltransferase.
AB  - The topography of rat glycerophosphate acyltransferase (GAT) in the transverse
      plane of the mitochondrial outer membrane (MOM) was investigated. Computer
      analysis of the amino acid (aa) sequence derived from rat mitochondrial GAT cDNA
      (GenBanktrade mark accession nos. and ) predicts the presence of two possible
      transmembrane domains (aa 473-493 and 574-594) separated by an 80-aa stretch (aa
      494-573). To determine the actual orientation of the native protein, we prepared
      anti-peptide antibodies to three regions: one in between (aa 543-559) and the
      other two (aa 420-435 and 726-740) flanking the two putative transmembrane
      regions. Both immunoreaction and immunoprecipitation experiments employing intact
      and solubilized mitochondria indicate that regions on the N- and C-terminal sides
      of the transmembrane regions are sequestered on the inner surface of the MOM,
      while the region between the transmembrane domains is present on the cytosolic
      face of the MOM. Additionally, two green fluorescent protein (GFP) fusion
      proteins consisting of full-length GAT fused to GFP at either the C terminus or
      inserted 115 amino acids from the N terminus were also constructed to determine
      the orientation of the N and C termini. COS-1 cells expressing these fusion
      proteins were fractionated to obtain mitochondria. Protease digestion of intact
      and solubilized COS-1 cell mitochondria revealed that the GFP domains of these
      fusion proteins are sequestered on the inner side of the MOM. The present
      findings indicate that GAT is a dual-spanning, transmembrane protein adopting an
      inverted "U" conformation in the transverse plane of the MOM, where the N and C
      termini are sequestered on the inner surface of the MOM, while aa 494-573 are
      exposed on the cytosolic surface of the MOM.

PMID- 10924501
TI  - The metabotropic GABAB receptor directly interacts with the activating
      transcription factor 4.
AB  - G protein-coupled receptors regulate gene expression by cellular signaling
      cascades that target transcription factors and their recognition by specific DNA
      sequences. In the central nervous system, heteromeric metabotropic gamma
      aminobutyric acid type B (GABA(B)) receptors through adenylyl cyclase regulate
      cAMP levels, which may control transcription factor binding to the cAMP response
      element. Using yeast-two hybrid screens of rat brain libraries, we now
      demonstrate that GABA(B) receptors are engaged in a direct and specific
      interaction with the activating transcription factor 4 (ATF-4), a member of the
      cAMP response element-binding protein /ATF family. As confirmed by pull-down
      assays, ATF-4 associates via its conserved basic leucine zipper domain with the C
      termini of both GABA(B) receptor (GABA(B)R) 1 and GABA(B)R2 at a site which
      serves to assemble these receptor subunits in heterodimeric complexes. Confocal
      fluorescence microscopy shows that GABA(B)R and ATF-4 are strongly coclustered in
      the soma and at the dendritic membrane surface of both cultured hippocampal
      neurons as well as retinal amacrine cells in vivo. In oocyte coexpression assays
      short term signaling of GABA(B)Rs via G proteins was only marginally affected by
      the presence of the transcription factor, but ATF-4 was moderately stimulated in
      response to receptor activation in in vivo reporter assays. Thus, inhibitory
      metabotropic GABA(B)Rs may regulate activity-dependent gene expression via a
      direct interaction with ATF-4.

PMID- 10924503
TI  - Role for p300 in Pax 8 induction of thyroperoxidase gene expression.
AB  - The nuclear p300 protein functions as a co-activator of gene transcription. Here
      we show that p300 works as a co-activator of the transcription factor Pax 8 on
      the thyroperoxidase gene promoter. Consistent with its role as co-activator, p300
      potentiates Pax 8-activated transcription. Furthermore, we provide evidence
      supporting the formation of a complex between both factors in vivo and in vitro.
      This interaction involves the amino-terminal and CH3 domains of p300 and the
      trans-activation domain of Pax 8 at its carboxyl-terminal end. We show that the
      CH3 domain is crucial for the co-activator role of p300 on the thyroperoxidase
      gene promoter. In agreement with our finding and with the ability of the
      adenoviral protein E1A to bind p300, we show that E1A down-regulates Pax 8
      activity.

PMID- 10924504
TI  - Cell type-dependent differences in thyroid peroxidase cell surface expression.
AB  - Recently, it has been suggested that only approximately 2% of human thyroid
      peroxidase (hTPO(933)) reaches the surface of stably transfected (Chinese hamster
      ovary) cells, most being degraded intracellularly, and this might be
      representative of thyroid peroxidase (TPO) behavior in thyrocytes (Fayadat, L.,
      Siffroi-Fernandez, S., Lanet, J., and Franc, J.-L. (2000) J. Biol. Chem. 275,
      15948-15954). In agreement, in stably transfected Madin-Darby canine kidney
      clones, nonpermeabilized cells exhibit wild-type hTPO(933) immunofluorescence
      (apically) on <10% of that found in permeabilized cells, where an endoplasmic
      reticulum pattern is observed. Further, a C-terminally truncated, membrane
      anchorless hTPO(848) is also retained in the endoplasmic reticulum of stably
      transfected Madin-Darby canine kidney cells. However, by contrast, in Chinese
      hamster ovary cells after transient transfection, hTPO(933) immunofluorescence is
      detected equally well in nonpermeabilized and permeabilized cells, indicating
      that a large portion of hTPO(933) is present at the cell surface; furthermore,
      hTPO(848) is efficiently secreted. Further, using an antiserum not cross-reacting
      with rat TPO, we find by immunofluorescence that in stable clones of PC Cl3 (rat)
      thyrocytes, considerably more ( approximately 50%) of the cells exhibit hTPO(933)
      at the cell surface. However, cell surface biotinylation and endoglycosidase H
      digestion assays appear to under-represent the extent of hTPO(933) transport,
      presumably because protein folding limits both Golgi carbohydrate modification
      and accessibility of lysines in the extracellular domain. We conclude that cell
      type-specific factors may facilitate stable expression of TPO at the cell surface
      of thyrocytes.

PMID- 10924505
TI  - Neuronal differentiation and growth control of neuro-2a cells after retroviral
      gene delivery of connexin43.
AB  - Given the roles proposed for gap junctional intercellular communication in
      neuronal differentiation and growth control, we examined the effects of
      connexin43 (Cx43) expression in a neuroblastoma cell line. A vesicular stomatitis
      virus G protein (VSVG)-pseudotyped retrovector was engineered to co-express the
      green fluorescent protein (GFP) and Cx43 in the communication-deficient neuro-2a
      (N2a) cell line. The 293 GPG packaging cell line was used to produce VSVG
      pseudotyped retrovectors coding for GFP, Cx43, or chimeric Cx43.GFP fusion
      protein. The titer of viral supernatant, as measured by flow cytometry for GFP
      fluorescence, was approximately 2.0 x 10(7) colony form units (CFU)/ml and was
      free of replication-competent retroviruses. After a 7-day treatment with retinoic
      acid (20 microm), N2a transformants (N2a-Cx43 and N2a-Cx43.GFP) maintained the
      expression of Cx43 and Cx43.GFP. Expression of both constructs resulted in
      functional coupling, as evidenced by electrophysiological and dye-injection
      analysis. Suppression of cell growth correlated with expression of both Cx43 or
      Cx43.GFP and retinoic acid treatment. Based on morphology and immunocytochemistry
      for neurofilament, no difference was observed in the differentiation of N2a cells
      compared with cells expressing Cx43 constructs. In conclusion, constitutive
      expression of Cx43 in N2a cells does not alter retinoic acid-induced neuronal
      differentiation but does enhance growth inhibition.

PMID- 10924506
TI  - Identification of GRIM-19, a novel cell death-regulatory gene induced by the
      interferon-beta and retinoic acid combination, using a genetic approach.
AB  - We show here that the combination of interferon-beta (IFN-beta) and all-trans
      retinoic acid (RA) induces the death of tumor cells. To understand the molecular
      basis for synergistic growth-suppressive action and to identify the gene products
      that participate in this process, we have employed an antisense knock-out
      technique. This approach permits the isolation of cell death-associated genes
      based on their selective inactivation by overexpression of antisense cDNAs.
      Because the antisense mRNA inactivates gene expression of death-specific genes,
      transfected cells survive in the presence death inducers. Several Genes
      associated with Retinoid-IFN-induced Mortality (GRIM) were identified using this
      approach. Here we report the isolation of a novel GRIM gene, GRIM-19. This 552
      base pair cDNA encodes a 16-kDa protein. Antisense expression of GRIM-19 confers
      a strong resistance against IFN/RA-induced death by reducing the intracellular
      levels of GRIM-19 protein. Overexpression of GRIM-19 enhances cell death in
      response to IFN/RA. GRIM-19 is primarily a nuclear protein whose expression is
      induced by the IFN/RA combination. Together, our studies identify a novel cell
      death-regulatory molecule.

PMID- 10924507
TI  - Specific interaction between RNA helicase A and Tap, two cellular proteins that
      bind to the constitutive transport element of type D retrovirus.
AB  - Constitutive transport element (CTE) facilitates retroviral RNA export by
      interacting with the cellular RNA export machinery. Two cellular proteins, RNA
      helicase A (RHA) and Tip-associated protein (Tap) were identified as binding to
      CTE and were proposed to function as CTE co-factors (1,2). Here, we report that
      these two CTE-binding proteins interact with each other in vitro and in vivo. The
      in vitro binding of RHA to Tap is direct and independent of either CTE or the
      nuclear transport domain of RHA. The removal of the first 60 amino acids of Tap
      significantly diminishes the binding to RHA. The activity of this Tap mutant to
      enhance CTE-mediated gene expression is also markedly reduced. A transdominant
      mutant of Tap inhibited RHA-mediated up-regulation of CTE function in mammalian
      cells. The nuclear transport domain of RHA also interfered with Tap-mediated
      transactivation of the CTE function in quail cells, in which the function of CTE
      is dependent on the expression of a functional human Tap cDNA.

PMID- 10924508
TI  - Pathogenic alpha 1-antitrypsin polymers are formed by reactive loop-beta-sheet A
      linkage.
AB  - alpha(1)-Antitrypsin is the most abundant circulating protease inhibitor and the
      archetype of the serine protease inhibitor or serpin superfamily. Members of this
      family may be inactivated by point mutations that favor transition to a polymeric
      conformation. This polymeric conformation underlies diseases as diverse as
      alpha(1)-antitrypsin deficiency-related cirrhosis, thrombosis, angio-edema, and
      dementia. The precise structural linkage within a polymer has been the subject of
      much debate with evidence for reactive loop insertion into beta-sheet A or C or
      as strand 7A. We have used site directed cysteine mutants and fluorescence
      resonance energy transfer (FRET) to measure a number of distances between
      monomeric units in polymeric alpha(1)-antitrypsin. We have then used a
      combinatorial approach to compare distances determined from FRET with distances
      obtained from 2.9 x 10(6) different possible orientations of the alpha(1)
      antitrypsin polymer. The closest matches between experimental FRET measurements
      and theoretical structures show conclusively that polymers of alpha(1)
      antitrypsin form by insertion of the reactive loop into beta-sheet A.

PMID- 10924509
TI  - Cellular responses and repair of single-strand breaks introduced by UV damage
      endonuclease in mammalian cells.
AB  - Although single-strand breaks (SSBs) occur frequently, the cellular responses and
      repair of SSB are not well understood. To address this, we established mammalian
      cell lines expressing Neurospora crassa UV damage endonuclease (UVDE), which
      introduces a SSB with a 3'-OH immediately 5' to UV-induced cyclobutane pyrimidine
      dimers or 6-4 photoproducts and initiates an alternative excision repair process.
      Xeroderma pigmentosum group A cells expressing UVDE show UV resistance of almost
      the wild-type level. In these cells SSBs are produced upon UV irradiation and
      then efficiently repaired. The repair patch size is about seven nucleotides, and
      repair synthesis is decreased to 30% by aphidicolin, suggesting the involvement
      of a DNA polymerase delta/epsilon-dependent long-patch repair. Immediately after
      UV irradiation, cellular proteins are poly(ADP-ribosyl)ated. The UV resistance of
      the cells is decreased in the presence of 3-aminobenzamide, an inhibitor of
      poly(ADP-ribose) polymerase. Expression of UVDE in XRCC1-defective EM9, a Chinese
      hamster ovary cell line, greatly sensitizes the host cells to UV, and addition of
      3-aminobenzamide results in almost no further sensitization of the cells to UV.
      Thus, we show that XRCC1 and PARP are involved in the same pathway for the repair
      of SSBs.

PMID- 10924511
TI  - Porcine microsomal vitamin D(3) 25-hydroxylase (CYP2D25). Catalytic properties,
      tissue distribution, and comparison with human CYP2D6.
AB  - The metabolic activation of the prohormone vitamin D(3) requires a 25
      hydroxylation that has been reported to be catalyzed by both mitochondrial CYP27A
      and a microsomal vitamin D(3) 25-hydroxylase in the liver. CYP27A has been
      extensively studied, but its role as a physiologically important vitamin D(3) 25
      hydroxylase has been questioned. The present paper reports that the microsomal
      vitamin D(3) 25-hydroxylase, purified from pig liver, converted vitamin D(3) into
      25-hydroxyvitamin D(3) in substrate concentrations which are within the
      physiological range (apparent K(m) = 0.1 microm). The enzyme 25-hydroxylated
      vitamin D(3), 1 alpha-hydroxyvitamin D(3) and vitamin D(2) and also converted
      tolterodine, a substrate for human CYP2D6, into its 5-hydroxymethyl metabolite.
      Tolterodine inhibited the microsomal 25-hydroxylation, whereas quinidine, an
      inhibitor of CYP2D6, did not markedly inhibit the reaction. The primary structure
      of the microsomal vitamin D(3) 25-hydroxylase, designated CYP2D25, shows 77%
      identity with that of human CYP2D6. Northern blot and reverse transcription
      polymerase chain reaction experiments revealed that CYP2D25 mRNA is expressed in
      higher levels in liver than in kidney and in small amounts in adrenals, brain,
      heart, intestine, lung, muscle, spleen, and thymus. Experiments with human liver
      microsomes and recombinantly expressed CYP2D6 strongly indicate that the
      microsomal 25-hydroxylation of vitamin D(3) in human liver is catalyzed by an
      enzyme different from CYP2D6.

PMID- 10924510
TI  - Maturation and endosomal targeting of beta-site amyloid precursor protein
      cleaving enzyme. The Alzheimer's disease beta-secretase.
AB  - The amyloidogenic Abeta peptide is liberated from the amyloid precursor protein
      (APP) by two proteolytic activities, beta-secretase and gamma-secretase.
      Recently, a type I membrane protein termed BACE (beta-site APP cleaving enzyme)
      with characteristics of an aspartyl protease has been identified as the beta
      secretase. We undertook a series of biochemical and morphological investigations
      designed to characterize the basic properties of this protein. Initial studies
      indicated that BACE undergoes N-linked glycosylation at three of four potential
      sites. Metabolic pulse-chase experiments revealed that after core glycosylation,
      BACE is rapidly and efficiently transported to the Golgi apparatus and distal
      secretory pathway. BACE was also found to be quite stable, being turned over with
      a t(12) of approximately 16 h. Retention of BACE in the endoplasmic reticulum by
      introduction of a C-terminal dilysine motif prevented complex carbohydrate
      processing and demonstrated that propeptide cleavage occurs after exit from this
      organelle. BACE exhibited intramolecular disulfide bonding but did not form
      oligomeric structures by standard SDS-polyacrylamide gel electrophoresis analysis
      and sedimented as a monomer in sucrose velocity gradients. Immunofluorescence
      studies showed a largely vesicular staining pattern for BACE that colocalized
      well with endosomal, but not lysosomal, markers. Measurable levels of BACE were
      also detected on the plasma membrane by both immunostaining and cell surface
      biotinylation, and cycling of the protein between the cell membrane and the
      endosomes was documented. A cytoplasmic dileucine motif was found to be necessary
      for normal targeting of BACE to the endosomal system and accumulation of the
      protein in this intracellular site.

PMID- 10924512
TI  - Flavopiridol inhibits glycogen phosphorylase by binding at the inhibitor site.
AB  - Flavopiridol (L86-8275) ((-)-cis-5, 7-dihydroxy-2-(2-chlorophenyl)-8-[4-(3
      hydroxy-1-methyl)-piperidinyl] -4H-benzopyran-4-one), a potential antitumor drug,
      currently in phase II trials, has been shown to be an inhibitor of muscle
      glycogen phosphorylase (GP) and to cause glycogen accumulation in A549 non-small
      cell lung carcinoma cells (Kaiser, A., Nishi, K., Gorin, F.A., Walsh, D.A.,
      Bradbury, E. M., and Schnier, J. B., unpublished data). Kinetic experiments
      reported here show that flavopiridol inhibits GPb with an IC(50) = 15.5 microm.
      The inhibition is synergistic with glucose resulting in a reduction of IC(50) for
      flavopiridol to 2.3 microm and mimics the inhibition of caffeine. In order to
      elucidate the structural basis of inhibition, we determined the structures of GPb
      complexed with flavopiridol, GPb complexed with caffeine, and GPa complexed with
      both glucose and flavopiridol at 1.76-, 2.30-, and 2.23-A resolution, and refined
      to crystallographic R values of 0.216 (R(free) = 0.247), 0.189 (R(free) = 0.219),
      and 0.195 (R(free) = 0.252), respectively. The structures provide a rational for
      flavopiridol potency and synergism with glucose inhibitory action. Flavopiridol
      binds at the allosteric inhibitor site, situated at the entrance to the catalytic
      site, the site where caffeine binds. Flavopiridol intercalates between the two
      aromatic rings of Phe(285) and Tyr(613). Both flavopiridol and glucose promote
      the less active T-state through localization of the closed position of the 280s
      loop which blocks access to the catalytic site, thereby explaining their
      synergistic inhibition. The mode of interactions of flavopiridol with GP is
      different from that of des-chloro-flavopiridol with CDK2, illustrating how
      different functional parts of the inhibitor can be used to provide specific and
      potent binding to two different enzymes.

PMID- 10924513
TI  - Dinucleotide repeat expansion catalyzed by bacteriophage T4 DNA polymerase in
      vitro.
AB  - DNA replication normally occurs with high fidelity, but certain "slippery"
      regions of DNA with tracts of mono-, di-, and trinucleotide repeats are
      frequently mutation hot spots. We have developed an in vitro assay to study the
      mechanism of dinucleotide repeat expansion. The primer-template resembles a base
      excision repair substrate with a single nucleotide gap centered opposite a tract
      of nine CA repeats; nonrepeat sequences flank the dinucleotide repeats. DNA
      polymerases are expected to repair the gap, but further extension is possible if
      the DNA polymerase can displace the downstream oligonucleotide. We report here
      that the wild type bacteriophage T4 DNA polymerase carries out gap and strand
      displacement replication and also catalyzes a dinucleotide expansion reaction.
      Repeat expansion was not detected for an exonuclease-deficient T4 DNA polymerase
      or for Escherichia coli DNA polymerase I. The dinucleotide repeat expansion
      reaction catalyzed by wild type T4 DNA polymerase required a downstream
      oligonucleotide to "stall" replication and 3' --> 5' exonuclease activity to
      remove the 3'-nonrepeat sequence adjacent to the repeat tract in the template
      strand. These results suggest that dinucleotide repeat expansion may be
      stimulated in vivo during DNA repair or during processing of Okazaki fragments.

PMID- 10924514
TI  - p44/SSL1, the regulatory subunit of the XPD/RAD3 helicase, plays a crucial role
      in the transcriptional activity of TFIIH.
AB  - In order to unravel the mechanism that regulates transcription of protein-coding
      genes, we investigated the function of the p44 subunit of TFIIH, a basal
      transcription factor that is also involved in DNA repair. We have shown
      previously that mutations in the C terminus of the XPD helicase, another subunit
      of TFIIH, prevent its regulation by p44 (Coin, F., Bergmann, E., Tremeau-Bravard,
      A., and Egly, J. M. (1999) EMBO 18, 1357-1366). By using a site-directed
      mutagenesis approach within the p44 region from amino acids 66 to 200, we
      indicate how a decrease in the interaction between p44 and XPD results in a
      decrease of the XPD helicase activity and leads to a defect in the first steps of
      the transcription reaction, namely the first phosphodiester bond formation and
      promoter clearance. We thus provide some explanation for the transcriptional
      defect found in SSL1 mutated yeast (Wang, Z., Buratowski, S., Svejstrup, J. Q.,
      Feaver, W. J., Wu, X., Kornberg, R. D., Donahue, T. F., and Friedberg, E. C.
      (1995) Mol. Cell. Biol. 15, 2288-2293). Moreover, this study shows how the
      activity of the the cyclin-dependent kinase-activating kinase associated with
      TFIIH complex in stimulating transcription is mediated in part by p44/XPD
      interaction.

PMID- 10924515
TI  - Chemically regulated zinc finger transcription factors.
AB  - Ligand-dependent transcriptional regulators were generated by fusion of designed
      Cys(2)-His(2) zinc finger proteins and steroid hormone receptor ligand binding
      domains. To produce novel DNA binding domains, three-finger proteins binding
      specific 9-base pair sequences were constructed from modular building blocks.
      Fusion of these zinc finger proteins to a transcriptional activation domain and
      to modified ligand binding domains derived from either the estrogen or
      progesterone receptors yielded potent ligand-dependent transcriptional
      regulators. Together with optimized minimal promoters, these regulators provide 4
      hydroxytamoxifen- or RU486-inducible expression systems with induction ratios of
      up to 3 orders of magnitude. These inducible expression systems are functionally
      independent, and each can be selectively switched on within the same cell. The
      potential use of zinc finger-steroid receptor fusion proteins for the regulation
      of natural promoters was also explored. A gene-specific six-finger protein
      binding an 18-base pair target sequence was converted into a ligand-dependent
      regulator by fusion with either two estrogen receptor ligand binding domains or
      one ecdysone receptor and one retinoid X receptor ligand binding domain. These
      single-chain receptor proteins undergo an intramolecular rearrangement, rather
      than intermolecular dimerization and are functional as monomers. Thus, the
      ability to engineer DNA binding specificities of zinc finger proteins enables the
      construction of ligand-dependent transcriptional regulators with potential for
      the regulation of virtually any desired artificial or natural promoter. It is
      anticipated that the novel chemically regulated gene switches described herein
      will find many applications in applied and basic research, where the specific
      modulation of gene expression can be exploited.

PMID- 10924516
TI  - A new class of glutamate dehydrogenases (GDH). Biochemical and genetic
      characterization of the first member, the AMP-requiring NAD-specific GDH of
      Streptomyces clavuligerus.
AB  - A new class of glutamate dehydrogenase (GDH) is reported. The GDH of Streptomyces
      clavuligerus was purified to homogeneity and characterized. It has a native
      molecular mass of 1,100 kDa and exists as an alpha(6) oligomeric structure
      composed of 183-kDa subunits. GDH, which requires AMP as an essential activator,
      shows a maximal rate of catalysis in 100 mm phosphate buffer, pH 7.0, at 30
      degrees C. Under these conditions, GDH displayed hyperbolic behavior toward
      ammonia (K(m), 33 mm) and sigmoidal responses to changes in alpha-ketoglutarate
      (S(0.5) 1.3 mm; n(H) 1.50) and NADH (S(0.5) 20 microm; n(H) 1.52) concentrations.
      Aspartate and asparagine were found to be allosteric activators. This enzyme is
      inhibited by an excess of NADH or NH(4)(+), by some tricarboxylic acid cycle
      intermediates and by ATP. This GDH seems to be a catabolic enzyme as indicated by
      the following: (i) it is NAD-specific; (ii) it shows a high value of K(m) for
      ammonia; and (iii) when S. clavuligerus was cultured in minimal medium containing
      glutamate as the sole source of carbon and nitrogen, a 5-fold increase in
      specific activity of GDH was detected compared with cultures provided with
      glycerol and ammonia. GDH has 1,651 amino acids, and it is encoded by a DNA
      fragment of 4,953 base pairs (gdh gene). It shows strong sequence similarity to
      proteins encoded by unidentified open reading frames present in the genomes of
      species belonging to the genera Mycobacterium, Rickettsia, Pseudomonas, Vibrio,
      Shewanella, and Caulobacter, suggesting that it has a broad distribution. The GDH
      of S. clavuligerus is the first member of a class of GDHs included in a subfamily
      of GDHs (large GDHs) whose catalytic requirements and evolutionary implications
      are described and discussed.

PMID- 10924517
TI  - Regulation of the promoter activity of interferon regulatory factor-7 gene.
      Activation by interferon snd silencing by hypermethylation.
AB  - The molecular mechanism by which virus induces expression of the early
      inflammatory genes has not yet been completely elucidated. Previous studies
      indicated that the virus-mediated transcription of type I interferon (IFN) genes
      required activation of two members of IFN regulatory factor (IRF) family, IRF-3
      and IRF-7, where the expression of IRF-7 was found to be indispensable for the
      induction of IFNA genes. To determine the factors that regulate expression of IRF
      7 gene, as well as its inducibility by type I IFNs, we have isolated and
      characterized the promoter and first intron of the human IRF-7 gene. This region
      shows a presence of two potential interferon-sensitive response elements
      (ISRE/IRF-E). However, only the ISRE present in the first intron was functional
      and conferred interferon inducibility in a transient transfection assay. Using a
      pull-down assay with an oligodeoxynucleotide corresponding to this ISRE
      immobilized to magnetic beads, we have demonstrated that this ISRE binds ISGF3
      complex and IRF-1 from the extract of IFN-treated cells but not from the
      untreated cells. We have further shown that the previously observed lack of
      expression of IRF-7 in 2fTGH fibrosarcoma cell line, correlated with
      hypermethylation of the CpG island in the human IRF-7 promoter. The repression of
      the promoter activity was relieved by treatment with DNA methyltransferase
      inhibitor 5-aza-deoxycytidine. In vitro methylation of IRF-7 promoter silenced
      IRF-7 directed expression of luciferase gene in HeLa cells that express
      endogenous IRF-7 gene. Whether silencing of IRF-7 by methylation is instrumental
      for the process of tumorigenesis remains to be determined.

PMID- 10924518
TI  - Regulation of ribosome detachment from the mammalian endoplasmic reticulum
      membrane.
AB  - In current models, protein translocation in the endoplasmic reticulum (ER) occurs
      in the context of two cycles, the signal recognition particle (SRP) cycle and the
      ribosome cycle. Both SRP and ribosomes bind to the ER membrane as a consequence
      of the targeting process of translocation. Whereas SRP release from the ER
      membrane is regulated by the GTPase activities of SRP and the SRP receptor,
      ribosome release from the ER membrane is thought to occur in response to the
      termination of protein synthesis. We report that ER-bound ribosomes remain
      membrane-bound following the termination of protein synthesis and in the bound
      state can initiate the translation of secretory and cytoplasmic proteins. Two
      principal observations are reported. 1) Membrane-bound ribosomes engaged in the
      synthesis of proteins lacking a signal sequence are released from the ER membrane
      as ribosome-nascent polypeptide complexes. 2) Membrane-bound ribosomes
      translating secretory proteins can access the translocon in an SRP receptor
      independent manner. We propose that ribosome release from the ER membrane occurs
      in the context of protein translation, with release occurring by default in the
      absence of productive nascent polypeptide-membrane interactions.

PMID- 10924519
TI  - Valine, not methionine, is amino acid 106 in human cytosolic thymidine kinase
      (TK1). Impact on oligomerization, stability, and kinetic properties.
AB  - Cytosolic thymidine kinase (TK1) cDNA from human lymphocytes was cloned,
      expressed in Escherichia coli, purified, and characterized with respect to the
      ATP effect on thymidine affinity and oligomerization. Sequence analysis of this
      lymphocyte TK1 cDNA and 21 other cDNAs or genomic TK1 DNAs from healthy cells or
      leukemic or transformed cell lines revealed a valine at amino acid position 106.
      The TK1 sequence in NCBI GenBank(TM) has methionine at this position. The
      recombinant lymphocyte TK1(Val-106) (rLy-TK1(Val-106)) has the same enzymatic and
      oligomerization properties as endogenous human lymphocyte TK1 (Ly-TK1); ATP
      exposure induces an enzyme concentration-dependent reversible transition from a
      dimer to a tetramer with 20-30-fold higher thymidine affinity (K(m) about 15 and
      0.5 microm, respectively). Substitution of Val-106 with methionine to give rLy
      TK1(Met-106) results in a permanent tetramer with the high thymidine affinity
      (K(m) about 0.5 microm), even without ATP exposure. Furthermore, rLy-TK1(Met-106)
      is considerably less stable than rLy-TK1(Val-106) (t(12) at 15 degrees C is 41
      and 392 min, respectively). Because valine with high probability is the naturally
      occurring amino acid at position 106 in human TK1 and because this position has
      high impact on the enzyme properties, the Val-106 form should be used in future
      investigations of recombinant human TK1.

PMID- 10924520
TI  - Identification of two essential glutamic acid residues in glycogen synthase.
AB  - The detailed catalytic mechanism by which glycosyltransferases catalyze the
      transfer of a glycosyl residue from a donor sugar to an acceptor is not known.
      Through the multiple alignment of all known eukaryotic glycogen synthases we have
      found an invariant 17-amino acid stretch enclosed within the most conserved
      region of the members of this family. This peptide includes an E-X(7)-E motif,
      which is highly conserved in four families of retaining glycosyltransferases.
      Site-directed mutagenesis was performed in human muscle glycogen synthase to
      analyze the roles of the two conserved Glu residues (Glu-510 and Glu-518) of the
      motif. Proteins were transiently expressed in COS-1 cells as fusions to green
      fluorescence protein. The E510A and E518A mutant proteins retained the ability to
      translocate from the nucleus to the cytosol in response to glucose and to bind to
      intracellular glycogen. Although the E518A variant had approximately 6% of the
      catalytic activity shown by the green fluorescence protein-human muscle glycogen
      synthase fusion protein, the E510A mutation inactivated the enzyme. These results
      led us to conclude that the E-X(7)-E motif is part of the active site of
      eukaryotic glycogen synthases and that both conserved Glu residues are involved
      in catalysis. We propose that Glu-510 may function as the nucleophile and Glu-518
      as the general acid/base catalyst.

PMID- 10924521
TI  - Characterization of the Saccharomyces cerevisiae high affinity copper transporter
      Ctr3.
AB  - Copper is an essential nutrient required for the activity of a number of enzymes
      with diverse biological roles. In the bakers' yeast Saccharomyces cerevisiae,
      copper is transported into cells by two high affinity copper transport proteins,
      Ctr1 and Ctr3. Although Ctr1 and Ctr3 are functionally redundant, they bear
      little homology at the amino acid sequence level. In this report, we characterize
      Ctr3 with respect to its localization, assembly, and post-transcriptional
      regulation. Ctr3 is an integral membrane protein that assembles as a trimer to
      form a competent copper uptake permease at the plasma membrane. Whereas the CTR1
      and CTR3 genes are similarly regulated at the transcriptional level in response
      to copper, post-transcriptional regulation of these proteins is distinct. Unlike
      Ctr1, the Ctr3 transporter is neither regulated at the level of protein
      degradation nor endocytosis as a function of elevated copper levels. Our studies
      suggest that Ctr3 constitutes a fundamental module found in all eukaryotic high
      affinity copper transporters to date, which is sufficient for copper uptake but
      lacks elements for post-transcriptional regulation by copper.

PMID- 10924522
TI  - A binding site for the kringle II domain of prothrombin in the apple 1 domain of
      factor XI.
AB  - Previously we defined binding sites for high molecular weight kininogen (HK) and
      thrombin in the Apple 1 (A1) domain of factor XI (FXI). Since prothrombin (and
      Ca(2+)) can bind FXI and can substitute for HK (and Zn(2+)) as a cofactor for FXI
      binding to platelets, we have attempted to identify a prothrombin-binding site in
      FXI. The recombinant A1 domain (rA1, Glu(1)-Ser(90)) inhibited the saturable,
      specific and reversible binding of prothrombin to FXI, whereas neither the rA2
      domain (Ser(90)-Ala(181)), rA3 domain (Ala(181)-Val(271)), nor rA4 domain
      (Phe(272)-Glu(361)) inhibited prothrombin binding to FXI. Kinetic binding studies
      using surface plasmon resonance showed binding of FXI (K(d) approximately 71 nm)
      and the rA1 domain (K(d) approximately 239 nm) but not rA2, rA3, or rA4 to
      immobilized prothrombin. Reciprocal binding studies revealed that synthetic
      peptides (encompassing residues Ala(45)-Ser(86)) containing both HK- and thrombin
      binding sites, inhibit (125)I-rA1 (Glu(1)-Ser(90)) binding to prothrombin, (125)I
      prothrombin binding to FXI, and (125)I-prothrombin fragment 2 (Ser(156)-Arg(271))
      binding to FXI. However, homologous prekallikrein-derived peptides (encompassing
      Pro(45)-Gly(86)) did not inhibit FXI rA1 binding to prothrombin. The peptides
      Ala(45)-Arg(54), Phe(56)-Val(71), and Asp(72)-Ser(86), derived from sequences of
      the A1 domain of FXI, acted synergistically to inhibit (125)I-rA1 binding to
      prothrombin. Mutant rA1 peptides (V64A and I77A), which did not inhibit FXI
      binding to HK, retained full capacity to inhibit rA1 domain binding to
      prothrombin, and mutant rA1 peptides Ala(45)-Ala(54) (D51A) and Val(59)-Arg(70)
      (E66A), which did not inhibit FXI binding to thrombin, retained full capacity to
      inhibit rA1 domain binding to prothrombin. Thus, these experiments demonstrate
      that a prothrombin binding site exists in the A1 domain of FXI spanning residues
      Ala(45)-Ser(86) that is contiguous with but separate and distinct from the HK-
      and thrombin-binding sites and that this interaction occurs through the kringle
      II domain of prothrombin.

PMID- 10924523
TI  - The delta subunit of DNA polymerase III holoenzyme serves as a sliding clamp
      unloader in Escherichia coli.
AB  - In Escherichia coli, the circular beta sliding clamp facilitates processive DNA
      replication by tethering the polymerase to primer-template DNA. When synthesis is
      complete, polymerase dissociates from beta and DNA and cycles to a new start
      site, a primed template loaded with beta. DNA polymerase cycles frequently during
      lagging strand replication while synthesizing 1-2-kilobase Okazaki fragments. The
      clamps left behind remain stable on DNA (t(12) approximately 115 min) and must be
      removed rapidly for reuse at numerous primed sites on the lagging strand. Here we
      show that delta, a single subunit of DNA polymerase III holoenzyme, opens beta
      and slips it off DNA (k(unloading) = 0.011 s(-)(1)) at a rate similar to that of
      the multisubunit gamma complex clamp loader by itself (0.015 s(-)(1)) or within
      polymerase (pol) III* (0.0065 s(-)(1)). Moreover, unlike gamma complex and pol
      III*, delta does not require ATP to catalyze clamp unloading. Quantitation of
      gamma complex subunits (gamma, delta, delta', chi, psi) in E. coli cells reveals
      an excess of delta, free from gamma complex and pol III*. Since pol III* and
      gamma complex occur in much lower quantities and perform several DNA metabolic
      functions in replication and repair, the delta subunit probably aids beta clamp
      recycling during DNA replication.

PMID- 10924524
TI  - Human Ku antigen tightly binds and stabilizes a tetrahelical form of the Fragile
      X syndrome d(CGG)n expanded sequence.
AB  - Hairpin and tetrahelical structures of a d(CGG)(n) sequence in the FMR1 gene have
      been implicated in its expansion in fragile X syndrome. The identification of
      tetraplex d(CGG)(n) destabilizing proteins (Fry, M., and Loeb, L. A.(1999) J.
      Biol. Chem. 274, 12797-12803; Weisman-Shomer, P., Naot, Y., and Fry, M. (2000) J.
      Biol. Chem. 275, 2231-2238) suggested that proteins might modulate d(CGG)(n)
      folding and aggregation. We assayed human TK-6 lymphoblastoid cell extracts for
      d(CGG)(8) oligomer binding proteins. The principal binding protein was identified
      as Ku antigen by its partial amino acid sequence and antigenicity. The purified
      88/75-kDa heterodimeric Ku bound with similar affinities (K(d) approximately 1. 8
      10.2 x 10(-9) mol/liter) to double-stranded d(CGG)(8).d(CCG)(8), hairpin
      d(CGG)(8), single-stranded d(CII)(8), or tetraplex structures of telomeric or IgG
      switch region sequences. However, Ku associated more tightly with bimolecular G'2
      tetraplex d(CGG)(8) (K(d) approximately 0.35 x 10(-9) mol/liter). Binding to Ku
      protected G'2 d(CGG)(8) against nuclease digestion and impeded its unwinding by
      the tetraplex destabilizing protein qTBP42. Stabilization of d(CGG)(n) tetraplex
      domains in FMR1 by Ku or other proteins might promote d(CGG) expansion and FMR1
      silencing.

PMID- 10924525
TI  - The basic helix-loop-helix transcription factors dHAND and eHAND exhibit
      dimerization characteristics that suggest complex regulation of function.
AB  - dHAND and eHAND are basic helix-loop-helix (bHLH) transcription factors expressed
      during embryogenesis and are required for the proper development of cardiac and
      extraembryonic tissues. HAND genes, like the myogenic bHLH genes, are classified
      as class B bHLH genes, which are expressed in a tissue-restricted pattern and
      function by forming heterodimers with class A bHLH proteins. Myogenic bHLH genes
      are shown not to form homodimers efficiently, suggesting that their activity is
      dependent on their E-protein partners. To identify HIPs (HAND-interacting
      proteins) that regulate the activity of the HAND genes, we screened an 9.5-10.5
      day-old mouse embryonic yeast two-hybrid library with eHAND. Several HIPs held
      high sequence identity to eHAND, indicating that eHAND could form and function as
      a homodimer. Based on the high degree of amino acid identity between eHAND and
      dHAND, it is possible that dHAND could also form homodimers and heterodimers with
      eHAND. We show using yeast and mammalian two-hybrid assays as well as biochemical
      pull-down assays that eHAND and dHAND are capable of forming both HAND homo- and
      heterodimers in vivo. To investigate whether HAND genes form heterodimers with
      other biologically relevant bHLH proteins, we tested and show HAND
      heterodimerization with the recently identified Hairy-related transcription
      factors, HRT1-3. This finding is exciting, because both HRT and HAND genes are
      coexpressed in the developing heart and limb and both have been implicated in
      establishing tissue boundaries and pattern formation. Moreover, competition gel
      shift analysis demonstrates that dHAND and eHAND can negatively regulate the DNA
      binding of MyoD/E12 heterodimers in a manner similar to MISTI and Id proteins,
      suggesting a possible transcriptional inhibitory role for HAND genes. Taken
      together, these results show that dHAND and eHAND can form homo- and heterodimer
      combinations with multiple bHLH partners and that this broad dimerization profile
      reflects the mechanisms by which HAND genes regulate transcription.

PMID- 10924527
TI  - O-Glycosylation of nuclear and cytosolic proteins. Dynamic interplay between O
      GlcNAc and O-phosphate.

PMID- 10924528
TI  - G(olf)alpha mediates dopamine D1 receptor signaling.
AB  - It is generally assumed that the coupling of dopamine D1 receptors to adenylyl
      cyclase is mediated by the stimulatory GTP-binding protein G(s). However, the
      striatum contains little G(s)alpha subunit, whereas it expresses high levels of
      G(olf)alpha, a close relative of G(s)alpha that is also expressed in olfactory
      receptor neurons. We used G(olf)alpha knockout mice to examine the functional
      coupling of D1 receptors. We found that these mice showed no hyperlocomotor
      response to either the D1 agonist SKF-81297 or the psychostimulant cocaine.
      Moreover, G(olf)alpha knockout mice did not display cocaine-induced c-fos
      expression in the striatum. Finally, in the absence of G(olf)alpha, striatal D1
      receptors have a decreased affinity for dopamine. Thus coupling to G(olf)alpha
      appears to mediate D1 signaling in the striatum.

PMID- 10924530
TI  - Warfarin for multiple sclerosis?

PMID- 10924529
TI  - The dynamics of neuronal death: a time-lapse study in the retina.
AB  - Using time-lapse video microscopy, we have followed the process of neuronal death
      in an intact region of the mammalian nervous system. We show here the fast
      dynamics of nuclear fragmentation, which is over in <1 hr for neurons undergoing
      apoptosis in the living rat retina. Nuclear fragmentation is accompanied by a
      progressive raise of intracellular calcium and followed by erratic movement of
      the apoptotic cells, documenting their loss of adhesion.

PMID- 10924531
TI  - Management of osteoporosis in patients with hip fractures.

PMID- 10924532
TI  - The role of allergy in oral mucosal diseases.
AB  - We retrospectively assessed the prevalence of positive results to cutaneous patch
      testing, and the relevance of exclusion of identified allergens in the disease
      process, in 1252 patients with oral mucosal diseases presenting to the Department
      of Oral Medicine in Glasgow Dental Hospital and School and referred to the
      Contact Dermatitis Investigation Unit in Glasgow Royal Infirmary. The prevalence
      of patch-test positivity in each disease cohort was compared with that in 100
      control volunteers. Patients with oral mucosal diseases were significantly more
      likely to have demonstrable hypersensitivity to food additives, especially
      benzoic acid, and perfumes and flavourings, especially cinnamaldehyde, than
      controls, and avoidance therapy caused improvement in the majority. Patch testing
      and the resultant avoidance therapy are useful adjuncts in the management of oral
      mucosal diseases.

PMID- 10924533
TI  - Analysis of risk factors involved in oral-anticoagulant-related intracranial
      haemorrhages.
AB  - We examined risk factors for intracranial bleeding while on oral anticoagulants
      (OACs) in 68 patients admitted to hospital over a 6-year period, and 204 out
      patient controls followed-up in an OAC clinic. Under multivariate analysis,
      significant risk factors for OAC-related intracranial bleeds were hypertension
      (OR (95%CI) 2.69 (1.04-6.97), duration of OAC therapy < or =12 months (OR 3.74
      (1.21-11.56)), duration > or =96 months (OR 0.25 (0.07-0.88)), and International
      Normalized Ratio on admission >4.5 (OR 10.92 (2.46-48.43)). A logistic regression
      model including the above variables along with a history of 'cerebrovascular
      disease' (OR 2.32 (0.98-5.46)) correctly predicted intracranial bleeding (or its
      absence) during OAC therapy in 85% of all patients. The risk associated with
      advanced age and concomitant aspirin use was not significantly increased in this
      analysis. It is important to achieve tight control of INR, particularly in the
      early months of treatment. Patients with previous cerebrovascular disease are at
      increased risk of intracranial bleeding on warfarin, and hypertensive patients
      should have especially close monitoring and optimal control of their blood
      pressure.

PMID- 10924534
TI  - Prognostic factors and clustering of serious clinical outcomes in
      antiphospholipid syndrome.
AB  - We assessed whether initial clinical presentations suggestive of antiphospholipid
      syndrome (APS) predicted the subsequent rate and type of serious clinical
      outcomes. Eighty-two consecutive patients with anticardiolipin antibodies or
      lupus anticoagulant were followed for 814 person-years after a first event
      suggestive of APS (livedo reticularis, thrombocytopenia, autoimmune haemolysis,
      thrombosis, central nervous system manifestations, recurrent abortions). The
      hazard of developing a second event was largest in patients with antibodies
      recognizing beta2 glycoprotein I who had autoimmune haemolysis as the first event
      (hazard ratio HR 2.70, p=0.018) and smallest in patients without such antibodies
      who had recurrent abortions as their first event (HR 0.37, p=0.028). Subsequent
      serious events in patients with venous and arterial thromboses, recurrent
      abortions, central nervous system manifestations and autoimmune haemolytic
      anaemia were likely to be of the same type as the presenting event (odds ratio
      (OR) 3.76, 5.90, 77.7, 6.92, and 7.13, respectively. Adjusting for therapy, the
      rate of subsequent serious events was 6.86-fold higher (p=0.0001) in patients
      presenting with two events, 1.56-fold higher (p=0.038) in autoimmune haemolysis
      presentations, 1.69-fold higher (p=0.004) in patients with anti-beta2
      glycoprotein-I antibodies, and 46% (p=0.063) lower in thrombocytopenia
      presentations. Initial clinical features determine the long-term evolution of
      APS, and specific types of clinical manifestations cluster during the course of
      the disease.

PMID- 10924535
TI  - Clinical features, diagnosis and outcome of acute portal vein thrombosis.
AB  - The clinical features of acute portal vein thrombosis (APVT) are poorly defined
      in the literature. The proportion that progress to chronic PVT and the influences
      of various treatments are unknown. Between 1996 and 1998, nine patients presented
      to our hospital with varying upper gastrointestinal symptoms. They were found to
      have APVT by colour flow Doppler ultrasound, which was confirmed by CT scanning.
      All were tested for procoagulant tendencies and then treated with intravenous
      heparin for 7 days and warfarin for 3 months. Colour flow Doppler ultrasound or
      CT was done regularly to assess response to treatment. There was complete
      resolution of thrombus in five patients. Four patients had procoagulant
      tendencies identified; of these the thrombus resolved in two cases and in two
      cavernous transformation occurred. In most cases, the thrombus disperses on
      heparin and warfarin, although the effect of this therapy is unknown. A
      randomized trial of thrombolytic therapy may be appropriate, in an attempt to
      reduce the rate of progression to chronic PVT.

PMID- 10924536
TI  - Presentation, survival and prognostic markers in AA amyloidosis.
AB  - We reviewed 43 patients with AA amyloidosis who presented to our unit between
      1985-1999: 70% had an underlying chronic rheumatological diagnosis. Median (95%
      CI) patient survival from time of diagnosis was 52.9 months (9.4-96.6) and median
      renal survival was 18 months (3.2-32.8) Twenty-four patients have died; 42% of
      deaths were due to infection, while renal failure accounted for 12.5%. Presenting
      factors which adversely influenced outcome were a low serum albumin and a high 24
      h urinary albumin excretion (p=0.007 and p=0.003, respectively). Stepwise
      multivariate regression analysis identified albuminuria and presenting creatinine
      clearance as significant predictors. (p=0.005 and p=0.035, respectively). Mean C
      reactive protein (CRP) throughout follow-up correlated weakly but not
      significantly with survival off dialysis (p=0.06). Change in creatinine clearance
      correlated with albuminuria. (r(2)=40%, p=0.001)

PMID- 10924537
TI  - Are oesophageal disorders a common cause of chest pain despite normal coronary
      anatomy?

PMID- 10924538
TI  - Hydrocarbon exposure may cause glomerulonephritis and worsen renal function:
      evidence based on Hill's criteria for causality.
AB  - Many observational and experimental studies point to hydrocarbon exposure as an
      important pathogenic factor in glomerulonephritis. The findings have made little
      impact on current concepts and patient care, possibly because the hypothesis of a
      direct causal effect of the exposure and the hypothesis that the exposure worsens
      renal function have not been considered separately. This review examines these
      two hypotheses using Hill's criteria for causality. The results from 14 cross
      sectional, 18 case-control studies, two cohort studies, 15 experiments on
      laboratory animals and two on human beings together with many case reports
      satisfy all but one of Hill's criteria for both hypotheses. Of particular
      importance is the finding in the case-control and follow-up studies of an
      association between degree of exposure and stage of renal disease, and an inverse
      association between degree of exposure and renal function, indicating that the
      most important effect of hydrocarbon exposure is its effect on renal function.
      End-stage renal failure may be preventable in many patients with
      glomerulonephritis provided a possible exposure to toxic chemicals is
      discontinued.

PMID- 10924539
TI  - Systolic and diastolic blood pressures and urinary sodium excretion in mainland
      China.

PMID- 10924540
TI  - Pulmonary embolism-an update on thrombolytic therapy.

PMID- 10924541
TI  - Thymoma, autoimmunity and fatal immunodeficiency.

PMID- 10924542
TI  - Primary hyperthyroidism due to a parathyroid adenoma with subsequent myasthenia
      gravis.

PMID- 10924543
TI  - Musculoskeletal radiology: then and now.
AB  - Musculoskeletal radiologists, owing to recent advances in imaging technologies
      and techniques, are playing an increasingly important role in documenting,
      diagnosing, and treating an increasing variety of bone and soft-tissue lesions.
      However, improved visualization of anatomic aberrations-"seeing better"-must be
      paired with "knowing more," on the basis of complete familiarity with all aspects
      of the biology, physiology, pathophysiology, and static anatomy of the
      musculoskeletal system. Only with foreknowledge of the latter can the
      musculoskeletal radiologist fully maximize the benefits of the former.

PMID- 10924544
TI  - New horizons in pediatric radiology.

PMID- 10924545
TI  - The future of pediatric radiology.

PMID- 10924546
TI  - Focus on imaging at the American Heart Association annual meeting.

PMID- 10924547
TI  - Suspension of breast-feeding following gadopentetate dimeglumine administration.

PMID- 10924548
TI  - The Radiological Society of North America 86th scientific assembly and annual
      meeting Sunday, November 26 to Friday, December 1, 2000 McCormick place, Chicago,
      Illinois.

PMID- 10924549
TI  - Award-winning papers and honored lectures

PMID- 10924550
TI  - CT colonography: the next colon screening examination?
AB  - Computed tomographic (CT) colonography is a new-generation technique for
      detecting colorectal neoplasms by using volumetric CT data combined with
      specialized imaging software. Patient examinations require full colonic
      preparation, insufflation, and data acquisition with the patient in the supine
      and prone positions. Current CT technology allows a single image of the colon to
      be acquired in as little as 20 seconds with a minimum of patient discomfort.
      Specialized computer software for interpretation usually combines transverse,
      multiplanar reformation, and three-dimensional endoluminal images for the optimal
      visualization of the colon and rectum. As of the time this article was written,
      CT colonography was competitive as a full structural colonic examination for the
      detection of polyps and cancer. To the authors' knowledge, no study results have
      yet been reported in a screening population. The unique capabilities of CT
      colonography include the display of the proximal colon that is inaccessible at
      colonoscopy because of obstructing colonic lesions or because of incomplete
      endoscopic examinations and the assessment of extracolonic abdominal and pelvic
      organs. This abdominopelvic survey potential provides radiologists with an
      opportunity to discover other potentially life-threatening, asymptomatic
      conditions. Further technologic developments and validation studies are in
      progress. CT colonography is an exciting and promising technique with an enormous
      potential for colorectal screening in the future.

PMID- 10924551
TI  - Imaging of tinnitus: a review.
AB  - Tinnitus, a buzzing or ringing in the ear, may be pulsatile or continuous
      (nonpulsatile). The distinction, with a detailed clinical evaluation, determines
      the most appropriate imaging study. Pulsatile tinnitus suggests a vascular
      neoplasm, vascular anomaly, or vascular malformation. Most of the neoplasms are
      glomus tympanicum and glomus jugulare tumors. Vascular anomalies may cause
      pulsatile tinnitus, but the mechanism is unknown, and another (treatable) cause
      should be sought. Most neoplasms and anomalies are best seen on bone algorithm
      computed tomographic (CT) studies. Dural vascular malformations are often elusive
      on all cross-sectional imaging studies; conventional angiography may be necessary
      to make this diagnosis. Flow-sensitive magnetic resonance (MR) images show
      vascular loops compressing the eighth cranial nerve. Carotid dissections,
      aneurysms, atherosclerosis, and fibromuscular dysplasia can be identified on both
      MR imaging or MR angiographic studies and CT or CT angiographic studies.
      Otosclerosis and Paget disease are CT diagnoses. Benign intracranial hypertension
      often has no abnormal imaging findings. For patients with nonpulsatile tinnitus,
      MR imaging is the study of choice to exclude a vestibular schwannoma or other
      neoplasm of the cerebellopontine angle cistern. Multiple sclerosis and a Chiari I
      malformation are rare causes of pulsatile tinnitus, also best seen on MR studies.
      Many patients with tinnitus have no abnormal imaging findings.

PMID- 10924552
TI  - Multiple sclerosis: magnetization transfer histogram analysis of segmented normal
      appearing white matter.
AB  - PURPOSE: To investigate and characterize the global distribution of magnetization
      transfer (MT) ratio values of normal-appearing white matter (NAWM) in patients
      with relapsing-remitting multiple sclerosis (MS) and test the hypothesis that the
      MT histogram for NAWM reflects disease progression. MATERIALS AND METHODS:
      Conventional and MT magnetic resonance (MR) images were obtained in 23 patients
      and 25 healthy volunteers. Clinical tests for comparison with the MT histogram
      parameters included the Extended Disability Status Scale and the ambulation
      index. Lesion load calculated with T2-weighted MR images and whole-brain and
      white matter volumes were measured. RESULTS: The location of the MT histogram
      peak and the mean MT ratio for NAWM were significantly lower in patients with MS
      than in control subjects. In longitudinal studies, the histogram peak location
      and mean MT ratio shifted in the direction of normal values as the duration of
      disease increased. A mean of 26.5% of the volume of new lesions identified on the
      later studies were demonstrated to have originated in NAWM corresponding to
      "lost" pixels on the histogram. CONCLUSION: MT histogram analysis of NAWM,
      including longitudinal analysis, may provide new prognostic information regarding
      lesion formation and increase understanding of the course of the disease.

PMID- 10924553
TI  - Diagnosis of arterial injuries caused by penetrating trauma to the neck:
      comparison of helical CT angiography and conventional angiography.
AB  - PURPOSE: To determine the sensitivity and specificity of helical computed
      tomographic (CT) angiography in the diagnosis of carotid and vertebral arterial
      injuries caused by penetrating neck trauma. MATERIALS AND METHODS: A prospective
      study was conducted during 24 months in 60 patients with penetrating neck trauma
      who were referred for conventional angiography owing to clinical suspicion of
      arterial injury. In the patient population, 146 arteries (77 carotid, 69
      vertebral) were studied by means of conventional angiography. In all patients,
      conventional angiography and helical CT angiography were completed within 6
      hours. Two radiologists interpreted helical CT angiographic studies by means of
      consensus. Conventional angiography was the standard of reference for determining
      the sensitivity and specificity of helical CT angiography. RESULTS: Conventional
      angiograms showed arterial injuries in 10 (17%) of 60 patients. Conventional
      angiographic findings were arterial occlusion (n = 4), arteriovenous fistula (n =
      2), pseudoaneurysm (n = 3), pseudoaneurysm with arteriovenous fistula (n = 1),
      and normal arteries (n = 136). Nine of 10 arterial injuries and all normal
      arteries were depicted adequately at helical CT angiography. Sensitivity of
      helical CT angiography was 90%, specificity was 100%, positive predictive value
      was 100%, and negative predictive value was 98%. CONCLUSION: The sensitivity and
      specificity of helical CT angiography are high for detection of major carotid and
      vertebral arterial injuries resulting from penetrating trauma.

PMID- 10924555
TI  - Recurrent head and neck cancer: retreatment of previously irradiated areas with
      combined chemotherapy and radiation therapy-results of a prospective study.
AB  - PURPOSE: To prospectively test the effectiveness of combined chemotherapy and
      radiation therapy for recurrent head and neck cancer. MATERIALS AND METHODS: In
      32 patients, external-beam radiation therapy (2 Gy/d) was administered as a 5-day
      course with simultaneous hydroxyurea (1.5 g/d orally) and 5-fluorouracil (300
      mg/m(2)/d bolus), followed by 9 days of rest. This cycle was repeated until a
      cumulative soft-tissue radiation dose of 110 Gy (including prior radiation
      therapy) was reached. RESULTS: At a median follow-up of 18 months, three patients
      were alive, and 29 had died. The overall 1-year survival rate was 39%. The
      overall response rate was 41% (13 patients). Acute toxicity was low. According to
      World Health Organization and Radiation Therapy Oncology Group criteria, there
      were three cases of grade 3 mucositis or dermatitis and three cases of grade 3 or
      4 neutropenia. Three patients had grade 3 late effects: one oral trismus, one
      jugular venous thrombosis, and one cerebral stroke. CONCLUSION: The combination
      of simultaneous 5-fluorouracil and hydroxyurea infusion and local reirradiation
      is feasible for retreatment of recurrent head and neck tumors. This regimen
      provides short-term tumor control in most patients and long-term control in a few
      patients.

PMID- 10924554
TI  - Posttransplantation lymphoproliferative disorder of the head and neck: imaging
      features in seven adults.
AB  - PURPOSE: To determine the cross-sectional imaging findings of posttransplantation
      lymphoproliferative disorder (PTLD) of the head and neck. MATERIALS AND METHODS:
      Computed tomographic (CT) scans (n = 6) and magnetic resonance (MR) images (n =
      2) in seven patients with histopathologically proved PTLD of the Waldeyer
      (lymphoid) ring or cervical lymph nodes were retrospectively reviewed for
      abnormalities. RESULTS: The interval between transplantation and PTLD onset was
      3.5-108 months (mean, 30 months). All patients had imaging abnormalities
      involving the Waldeyer ring, and focal 2.0-4. 5-cm masses were present in six
      patients (unilateral oropharyngeal tonsil in two, bilateral oropharyngeal tonsils
      in one, nasopharyngeal adenoids in three, unilateral pharyngeal tonsil and
      ipsilateral nasopharynx in one). In three patients, the mass was centrally low
      attenuating at CT or isointense to fluid at MR imaging, with enhancing solid
      peripheral lymphoid tissue. Three patients also had nodal findings: one with a 7
      cm low-attenuating nodal mass in the right neck and two with numerous bilateral
      lymph nodes (mostly normal sized) in the anterior and posterior cervical lymph
      chains. One patient also had a small mass in the upper mediastinum. CONCLUSION:
      In the setting of organ transplantation, findings of masses in the Waldeyer ring
      or an excessive number of cervical nodes should increase the index of suspicion
      of PTLD.

PMID- 10924556
TI  - Case 29

PMID- 10924557
TI  - Case 25: Joubert syndrome.

PMID- 10924558
TI  - Colonic masses: detection with MR colonography.
AB  - PURPOSE: To assess magnetic resonance (MR) colonography as a method for detection
      of colorectal masses, with conventional colonoscopy as the reference standard.
      MATERIALS AND METHODS: MR colonography was performed in 132 patients referred for
      colonoscopy because of the possible presence of a mass. After rectal filling with
      a gadopentetate dimeglumine and water enema, T1-weighted three-dimensional
      gradient-echo MR studies were acquired with the patient in the prone and supine
      positions. Water-sensitive single-shot fast spin-echo MR images were also
      obtained. Surface-rendered virtual endoscopic endoluminal views, orthogonal
      sections in three planes, and water-sensitive MR images were interactively
      assessed for presence of colorectal masses by two radiologists. RESULTS: MR
      colonography was well tolerated without sedation or analgesia. MR image quality
      was sufficient for diagnosis in 127 (96%) patients. Most small (</=5-mm-diameter)
      masses were overlooked at MR colonography, but 19 of 31 6-10-mm lesions and 26 of
      27 large (>10-mm) lesions were correctly identified. For these large masses, MR
      colonography had a sensitivity of 93%, specificity of 99%, positive predictive
      value of 92%, and negative predictive value of 98% for detection of masses.
      CONCLUSION: MR colonography is a promising modality for help in detecting
      colorectal mass lesions larger than 10 mm in diameter.

PMID- 10924559
TI  - Adjustable laparoscopic gastric banding in patients with morbid obesity:
      radiographic management, results, and postoperative complications.
AB  - PURPOSE: To determine the role of radiographic assessment in patients who
      underwent an adjustable laparoscopic gastric banding (ALGB) for the treatment of
      morbid obesity, and to evaluate the frequency and type of postoperative
      complications. MATERIALS AND METHODS: From September 1995 to March 1998, 98
      consecutive patients (18 men, 80 women; mean age, 39 years; age range, 22-62
      years) with morbid obesity (mean body weight, 132 kg; mean body mass index, 47.1
      kg/m(2)) underwent ALGB. In all patients, fluoroscopy was performed
      postoperatively to confirm band position and to exclude perforation and at 6-8
      weeks later to measure and adjust the stoma between the pouch and stomach for
      optimal weight loss. All patients underwent another examination 12 months
      postoperatively, whereas patients with unsatisfactory weight loss or patients
      suspected of having complications were examined earlier and on several occasions.
      RESULTS: Port puncture was feasible in all cases, and stomal adjustments could
      easily be repeated. Absolute (ie, total) weight loss after 1 year ranged from
      8.8% to 39.2% (mean, 18.3%). Twenty patients showed unsatisfactory weight loss.
      No early complications occurred. Late complications occurred in 34 patients and
      included pouch dilatation (concentric or eccentric with posterior slippage),
      eccentric band herniation, band penetration, disconnection, axial pouch
      herniation, and port-site infection. CONCLUSION: ALGB is an effective method in
      the treatment of morbid obesity. Radiographic assessments are crucial in the
      management of weight loss and detection of postoperative complications.

PMID- 10924560
TI  - Liver adenomatosis: clinical, histopathologic, and imaging findings in 15
      patients.
AB  - PURPOSE: To report and correlate the clinical, histopathologic, and imaging
      findings in 15 patients with liver adenomatosis. MATERIALS AND METHODS: Fifteen
      adult patients had more than 10 hepatic adenomas each and no history of glycogen
      storage disease or anabolic steroid use. Ten of them underwent bolus-enhanced
      dynamic computed tomography (CT) with or without magnetic resonance (MR) imaging,
      ultrasonography, and/or angiography. RESULTS: Clinical abnormalities included
      abdominal pain in 11 (73%) and hepatomegaly in 10 (67%) patients, and abnormal
      liver function in 10 (91%) of 11 patients. The number of adenomas in each patient
      was 10-50 at imaging, but many more lesions were found in the resected specimens.
      Hemorrhage was commonly found within adenomas at histopathologic analysis, but
      only four patients had clinical and imaging evidence of substantial hemorrhage.
      In all patients, the adenomas increased over time, and two patients developed
      hepatocellular carcinoma. CT and MR features of the adenomas included evidence of
      hypervascularity (63%), intratumoral fat (50% of patients at CT, 80% at MR), and
      decreased conspicuity at portal venous and delayed-phase imaging. Fifty percent
      of patients had congenital or acquired hepatic vascular abnormalities.
      CONCLUSION: The imaging and histopathologic features of individual adenomatous
      lesions are similar to those reported in young women who are taking oral
      contraceptives. However, the lesions in liver adenomatosis are not steroid
      dependent but rather multiple, progressive, and symptomatic, and they are more
      likely to lead to impaired liver function, hemorrhage, and perhaps malignant
      degeneration.

PMID- 10924561
TI  - Detection of focal liver lesions at biphasic spiral CT: randomized double-blind
      study of the effect of iodine concentration in contrast materials.
AB  - PURPOSE: To evaluate the effect of iodine concentration on the detection of focal
      liver lesions at biphasic spiral computed tomography (CT). MATERIALS AND METHODS:
      One hundred two patients (64 men, 38 women) with neoplastic (n = 85) and
      nonneoplastic focal lesions (n = 17) were prospectively assigned to biphasic
      injection group A or B and received 180 mL of iopromide containing 370 or 300 mg
      of iodine per milliliter, respectively, during spiral CT. Comparison included
      assessment of quantitative and qualitative parameters. RESULTS: Hepatic time
      attenuation curves and mean hepatic enhancement in the portal venous phase and
      aortic time-attenuation curves in both arterial and portal venous phases were
      statistically superior in group A compared with group B. There was no significant
      difference in the mean enhancement in all lesions in either group. In contrast,
      among patients with hepatocellular carcinoma, mean contrast enhancement in
      lesions in the arterial phase was significantly superior in group A compared with
      group B. Blinded readers classified hepatic attenuation and lesion visibility as
      very good and as improved significantly more often in group A than in group B.
      CONCLUSION: A decrease in iodine concentration significantly affects aortic and
      hepatic contrast enhancement and may impair the detectability of focal liver
      lesions during biphasic spiral CT.

PMID- 10924562
TI  - Hepatic tumors: contrast agent-enhancement patterns with pulse-inversion harmonic
      US.
AB  - PURPOSE: To evaluate contrast agent-enhancement patterns in hepatic hemangiomas,
      hepatic metastases, and hepatocellular carcinomas (HCCs) at pulse-inversion
      harmonic ultrasonography (US) with a microbubble contrast agent. MATERIALS AND
      METHODS: Twenty hepatic hemangiomas in 20 patients and 41 malignant hepatic
      tumors in 23 patients (33 metastases and eight HCCs) were evaluated with pulse
      inversion harmonic US. US images were obtained before injection and every 10-15
      seconds after injection of a 4-g bolus (300 mg/mL) of SH U 508A (a microbubble
      contrast agent) for 5 minutes. The contrast-enhancement patterns of 61 hepatic
      lesions were assessed. RESULTS: Of 20 hemangiomas, 19 revealed peripheral
      enhancement, which was globular in 14 (70%) and rimlike in five (25%), with
      centripetal fill-in; the remaining one (5%) showed homogeneous enhancement. In 33
      metastases, the enhancement was rimlike in 16 (48%), homogeneous in seven (21%),
      and stippled in two (6%); in the remaining eight metastases (24%), no enhancement
      was seen. Of eight HCCs, four (50%) showed homogeneous enhancement and the
      remaining four (50%) showed heterogeneous enhancement. Centripetal fill-in of
      lesions with intratumoral enhancement was not seen in any malignancy. CONCLUSION:
      Pulse-inversion harmonic US with a microbubble contrast agent is potentially
      useful for the specific diagnosis of hemangiomas that demonstrate characteristic
      enhancement features.

PMID- 10924563
TI  - CT criteria for management of blunt liver trauma: correlation with angiographic
      and surgical findings.
AB  - PURPOSE: To determine the contrast material-enhanced computed tomographic (CT)
      criteria for selection of hemodynamically stable patients with blunt hepatic
      injury for angiographic evaluation. MATERIALS AND METHODS: Seventy-two patients
      with blunt liver injury underwent CT and hepatic angiography. Hepatic injuries
      were graded with CT-based classification. Scans were assessed for evidence of
      contrast extravasation and laceration or contusion extending into the hepatic
      vein(s), inferior vena cava, porta hepatis, or gallbladder fossa. Medical,
      angiographic, and surgical records were reviewed to determine angiographic
      findings, surgical indications and findings, and outcomes. RESULTS: Compared with
      hepatic angiography, CT was 65% (11 of 17 patients) sensitive and 85% (41 of 48
      patients) specific for detection of arterial vascular injury. When CT severity
      grades 2 and 3 were analyzed, the sensitivity and specificity of CT were 100%
      (three of three patients) and 94% (34 of 36 patients), respectively (P <.001).
      Injury involving at least one major hepatic vein was found in 15 (88%) of 17
      patients who required liver-related surgery and in 23 (42%) of 55 of the other
      patients (P <.01). CONCLUSION: CT-based criteria, including hepatic injury grade,
      signs of arterial vascular injury, and presence or absence of major hepatic
      venous involvement assists in selecting patients for hepatic angiography and
      those at increased risk of ongoing or delayed hepatic bleeding or other
      posttraumatic complications.

PMID- 10924564
TI  - The steeple sign.

PMID- 10924565
TI  - Evaluation of suspected appendicitis in children and young adults: helical CT.
AB  - PURPOSE: To evaluate the accuracy of helical computed tomography (CT) for the
      diagnosis of appendicitis in children and to assess the utility of CT in
      establishing alternative diagnoses. MATERIALS AND METHODS: The medical records of
      154 children (median age, 12 years; age range, 1-20 years) who were suspected to
      have appendicitis and who underwent CT were reviewed. The gastrointestinal tract
      was opacified in 151 of 154 patients: Only orally administered contrast material
      was used in 126 patients; only rectally administered contrast material, in 21
      patients; and both oral and rectal contrast material, in four patients. CT
      findings were correlated with surgical and histopathologic findings or with
      clinical follow-up findings. RESULTS: Sixty-four CT scans were interpreted as
      positive for appendicitis and included 58 true-positive and six false-positive
      scans. Ninety scans were interpreted as negative and included 87 true-negative
      and three false-negative scans. CT had a sensitivity of 95% and a specificity of
      94% for the diagnosis of appendicitis. In addition, in 32 (34%) of 93 patients
      without appendicitis, an alternative diagnosis was established on the basis of CT
      findings. CONCLUSION: Helical CT is useful in a pediatric population to diagnose
      or exclude appendicitis and to establish an alternative diagnosis.

PMID- 10924566
TI  - Preoperative evaluation of living renal donors: comparison of CT angiography and
      MR angiography.
AB  - PURPOSE: To compare computed tomographic (CT) angiography and magnetic resonance
      (MR) angiography for preoperative evaluation of living renal donors. MATERIALS
      AND METHODS: Thirty-five living renal donors underwent preoperative contrast
      material-enhanced CT angiography and gadolinium-enhanced MR angiography. Each
      study was interpreted by two independent radiologists blinded to all other
      studies and to interpretations provided by other reviewers. Eighteen kidneys had
      surgical correlation. RESULTS: CT demonstrated 33 supernumerary arteries in 19
      patients, bilateral solitary arteries in 16 patients, and 18 proximal arterial
      branches in 16 patients. MR demonstrated 26 supernumerary arteries in 15
      patients, bilateral solitary renal arteries in 20 patients, and 21 proximal
      arterial branches in 16 patients. Interobserver agreements for MR (kappa = 0. 74)
      and CT (kappa = 0.73) were similar to the agreement between MR and CT (kappa =
      0.74). Among the kidneys chosen for nephrectomy, one small accessory artery and
      one proximal arterial branch were missed with CT and MR. Two of the accessory
      arteries suggested at CT were not found at nephrectomy. By averaging data for
      both modalities, supernumerary arteries were present in 49% of kidney donors and
      were bilateral in approximately 17%. Proximal arterial branches were present in
      46% of kidney donors. CONCLUSION: Preoperative CT and MR angiography of the renal
      arteries in renal donors demonstrate substantial agreement. Interobserver
      disagreement in the interpretation of CT and MR angiograms is related to 1-2-mm
      diameter vessels.

PMID- 10924568
TI  - Prediction of deep myometrial invasion in patients with endometrial cancer:
      clinical utility of contrast-enhanced MR imaging-a meta-analysis and Bayesian
      analysis.
AB  - PURPOSE: To determine if, in a patient with an endometrial cancer, in addition to
      the knowledge of tumor grade, preoperative magnetic resonance (MR) imaging
      findings contribute to treatment stratification and specialist referral.
      MATERIALS AND METHODS: By using a MEDLINE literature search and institutional
      pathology reports, pretest probabilities for myometrial invasion were correlated
      with tumor grade. Likelihood ratios (LRs) were obtained through summary receiver
      operating characteristics. RESULTS: The mean pretest probabilities of deep
      myometrial invasion were derived from seven articles (1,875 patients) and from
      125 institutional pathology reports. LRs for the prediction of myometrial
      invasion with contrast-enhanced MR imaging were derived from nine studies (742
      patients); positive and negative LRs were 10.11 and 0.1, respectively. The mean
      weighted pretest probabilities of deep myometrial invasion in patients with tumor
      grades 1, 2, or 3 were 13%, 35%, or 54%, respectively. Posttest probabilities of
      deep myometrial invasion for grades 1, 2, or 3 increased to 60%, 84%, or 92%,
      respectively, for positive and decreased to 1%, 5%, or 10%, respectively, for
      negative MR imaging findings. CONCLUSION: Use of contrast-enhanced MR imaging
      significantly affects the posttest probability of deep myometrial invasion in
      patients with all grades of endometrial cancer and could be used to select
      patients for specialist referral.

PMID- 10924567
TI  - Clinical outcome in female patients with pelvic pain and normal pelvic US
      findings.
AB  - PURPOSE: To understand the clinical outcome in patients with pelvic pain and
      negative pelvic ultrasonographic (US) findings. MATERIALS AND METHODS: Data from
      86 female patients with pelvic pain and normal pelvic US findings seen in a US
      section over a 15-month period were evaluated 6-21 months after US. Medical chart
      review follow-up was available in 86 patients, and telephone interview follow-up
      was conducted in 85 patients. We collected data on the outcome of pain;
      subsequent imaging, treatment, and surgery; and the duration of pain before US.
      RESULTS: Pelvic pain improved or resolved in 66 (77%) of the 86 patients. In the
      group with acute or subacute pain (duration </= 6 months), 62 (86%) of the 72
      patients (19 with acute pain and 53 with subacute pain) had improvement or
      resolution of symptoms. In the group with chronic pain (duration > 6 months),
      seven (50%) of the 14 patients had improved symptoms. Further imaging (13
      studies) was performed in nine patients: Twelve studies were normal, and one
      computed tomographic scan (1 month after the first US examination) showed
      diverticulitis. Eleven patients underwent 19 surgical procedures (endometrial
      sampling, hysteroscopy, laparoscopy, or hysterectomy). Four demonstrated
      clinically important disease (endometriosis and pelvic varices, endometriosis,
      adenomyosis, or pelvic adhesions). CONCLUSION: The majority of patients with
      pelvic pain and normal pelvic US findings had improvement or resolution of their
      symptoms, and those with acute or subacute pain were more likely to report
      improvement or resolution of pain than those with chronic pain. The yield of
      further imaging studies was low, and disease was identified in a minority of
      patients.

PMID- 10924569
TI  - Echogenic intracardiac focus in 2nd-trimester fetuses with trisomy 21: usefulness
      as a US marker.
AB  - PURPOSE: To determine whether there is a relationship between the presence of an
      echogenic intracardiac focus in 2nd-trimester fetuses and trisomy 21 (Down
      syndrome). MATERIALS AND METHODS: A complete genetic ultrasonographic (US) scan
      was obtained in 3,303 consecutive fetuses with an estimated gestational age of
      14.0-24.0 weeks (mean +/- SD, 17.1 weeks +/- 1.75). US was performed in a
      prospective fashion without any knowledge of karyotype and included assessment of
      any potential echogenic intracardiac focus (ie, calcified papillary muscle).
      Karyotypes were obtained in all fetuses. Maternal ages ranged from 13.0 to 47.4
      years (mean, 35.1 years +/- 5.1). The prevalence of Down syndrome in this
      population was 1.6% (53 of 3,303 fetuses). RESULTS: An echogenic intracardiac
      focus was seen in 147 of the 3,192 karyotypically normal fetuses (4.6%) and 16 of
      the 53 fetuses with trisomy 21 (30%). The positive predictive value (PPV) of an
      echogenic intracardiac focus in this high-risk population was 9.8%; sensitivity,
      30%; specificity, 95%; likelihood ratio, 6.6; and relative risk (RR), 8.2 (P
      <.001). For a sonographically isolated echogenic intracardiac focus, the PPV was
      3.7%; sensitivity, 19%; specificity, 95%; likelihood ratio, 4.2; and RR, 4.8 (P
      =.002). CONCLUSION: A sonographically isolated echogenic intracardiac focus (no
      other anomalies or markers noted on a complete genetic sonogram) was associated
      in our high-risk population with a 4.8-fold (95% CI: 1.8, 12.5) increase in RR
      for trisomy 21 (P =.002).

PMID- 10924570
TI  - In-plane coronary arterial motion velocity: measurement with electron-beam CT.
AB  - PURPOSE: To determine the speed of and changes in the speed of coronary arterial
      movement during the cardiac cycle with electron-beam computed tomography (CT).
      MATERIALS AND METHODS: With electron-beam CT, 20 consecutive cross-sectional
      images were acquired at the mid right coronary artery (with 50-msec acquisition
      time, 8-msec intersection delay, 7-mm section thickness, and intravenous
      administration of 40 mL of contrast agent) in 25 patients. On the basis of the
      displacement of the left anterior descending, left circumflex, and right coronary
      arterial cross sections from image to image, movement velocity in the transverse
      imaging plane was calculated and was correlated with the simultaneously recorded
      electrocardiogram. RESULTS: The velocity of in-plane coronary arterial motion
      varied considerably during the cardiac cycle. Peaks were caused by ventricular
      systole and diastole and by atrial contraction. The mean velocity was 46.6 mm/sec
      +/- 12. 5 (SD). The mean velocity of right coronary arterial movement (69.5
      mm/sec +/- 22.5) was significantly faster than that of the left anterior
      descending (22.4 mm/sec +/- 4.1) or the left circumflex coronary artery (48.4
      mm/sec +/- 15.0). The lowest mean velocity (27. 9 mm/sec) was at 48% of the
      cardiac cycle. CONCLUSION: The lowest velocity of coronary arterial movement,
      which displays considerable temporal variation, was at 48% of the cardiac cycle.

PMID- 10924572
TI  - Early bronchiolitis obliterans following lung transplantation: accuracy of
      expiratory thin-section CT for diagnosis.
AB  - PURPOSE: To evaluate the accuracy of thin-section computed tomography (CT) with
      expiratory scans in diagnosing early bronchiolitis obliterans after lung
      transplantation. MATERIALS AND METHODS: Thin-section CT scans were reviewed by
      two observers blinded to the diagnoses in seven consecutive lung transplant
      recipients with histopathologically proved bronchiolitis obliterans (group A) and
      21 with normal biopsy findings (group B). All patients had normal biopsy and
      stable pulmonary function test (PFT) results 2-36 weeks prior to CT. Patients
      with normal biopsy results were placed into subgroups based on abnormal (group
      B1) or stable (group B2) PFT results. Air-trapping extent on expiratory scans was
      scored on a 24-point scale. RESULTS: The mean air-trapping score in group A (6.6)
      was not significantly different from that in group B (4.5, P =. 17). The air
      trapping score was significantly higher in groups A and B1 than in group B2 (6.2
      and 2.6, respectively; P =.03). The frequency of an air-trapping score of 3 or
      more in groups A and B1 was significantly higher than that in group B2 (P =.03).
      By using a score of 3 or more to indicate air trapping, the sensitivity of
      expiratory CT was 74%, specificity was 67%, and accuracy was 71%. CONCLUSION:
      Thin-section CT, including expiratory scans, is of limited accuracy in diagnosing
      early bronchiolitis obliterans after lung transplantation.

PMID- 10924571
TI  - Patients with pulmonary fibrosis: cardiac function assessed with MR imaging.
AB  - PURPOSE: To detect abnormalities in cardiac function by using magnetic resonance
      (MR) imaging in patients with mild to moderate pulmonary fibrosis and to evaluate
      the relationship between pulmonary function and cardiac function. MATERIALS AND
      METHODS: Sixteen patients were compared with 16 sex- and age-matched healthy
      control subjects. Systolic function was assessed by using multisection multiphase
      cine MR imaging. Diastolic function was assessed with flow-sensitive MR imaging
      across the mitral and tricuspid valves. MR imaging results were compared with the
      severity of impairment in pulmonary function. RESULTS: Biventricular systolic
      function and left ventricular diastolic function were normal in patients, but
      right ventricular diastolic function was significantly impaired versus that of
      control subjects, with a ratio of peak flow during early diastolic (E) filling to
      peak flow during atrial contraction (A) of 0.85 +/- 0.40 versus 1.28 +/- 0.50 (P
      =.035). Biventricular E/A ratios were strongly correlated to age in patients and
      control subjects. The right ventricular E/A ratio in patients corresponded with
      values that are normally expected in people 20 years older. Diastolic left and
      right ventricular functions were significantly correlated with each other. There
      was no relationship between pulmonary function and cardiac function. CONCLUSION:
      Impairment of right ventricular diastolic function was found by using MR imaging
      in patients with mild to moderate pulmonary fibrosis, whereas left ventricular
      diastolic function and biventricular systolic function were preserved.

PMID- 10924573
TI  - Pseudochylous pleural effusion with fat-fluid levels: report of six cases.
AB  - The authors report the clinical and computed tomographic (CT) findings in six
      patients with chyliform pleural effusion. All six patients had a medical history
      of pleurisy before presentation; five of them had tuberculous pleural effusion.
      The CT scans of all six patients showed variable amounts of pleural fluid
      collection with a layering of fat at the nondependent site.

PMID- 10924574
TI  - Are screening serum creatinine levels necessary prior to outpatient CT
      examinations?
AB  - PURPOSE: To determine the percentage of outpatients with elevated serum
      creatinine levels (>/=2.0 mg/dL [177 micromol/L]) and associated reported risk
      factors for contrast material-induced nephrotoxic reactions (eg, diabetes, renal
      disease, male, age >/= 60 years, chemotherapy) who undergo computed tomography
      (CT) and to define a true high-risk population. MATERIALS AND METHODS: The serum
      creatinine levels were obtained in a total of 2,034 consecutive outpatients (969
      male, 1,065 female) who underwent contrast material-enhanced CT. In addition,
      selected patient charts were reviewed to determine the presence of risk factors
      for contrast material-induced nephrotoxic reactions. RESULTS: Only 66 (3.2%) had
      an elevated serum creatinine level. Risk factors were identified in 64 of the 66
      (97%) patients with an elevated serum creatinine level. Renal disease was present
      in 62 of the 66 (94%) patients. Two of the 66 patients with an elevated
      creatinine level had no identifiable risk factors, representing 0.1% of the total
      number of patients. CONCLUSION: The data suggest that the majority of patients
      with a serum creatinine level of at least 2.0 mg/dL (177 micromol/L) will be
      identified by screening for risk factors. Careful patient screening, especially
      for renal disease, at the time of scheduling could result in considerable savings
      in terms of radiology man-hours expended and laboratory costs.

PMID- 10924575
TI  - Cost-effectiveness of hepatic arterial chemoembolization for colorectal liver
      metastases refractory to systemic chemotherapy.
AB  - PURPOSE: To calculate the cost-effectiveness of hepatic arterial
      chemoembolization (HACE) for the treatment of colorectal liver metastases (CLM)
      over a range of survival benefits and to determine the survival benefit that HACE
      must confer to meet three thresholds of cost-effectiveness. MATERIALS AND
      METHODS: A spreadsheet model was used to estimate the marginal direct cost of
      HACE compared with palliative care from a payer's perspective. Medicare
      reimbursement amounts represented costs, while probabilities of reembolization
      and complications were obtained from records of patients who underwent HACE.
      Marginal cost-effectiveness was calculated from marginal direct cost by varying
      the survival benefit of HACE compared with palliative care from 0 to 24 months.
      Break-even analyses were conducted to determine the survival benefit at which the
      cost-effectiveness of HACE would decrease below three threshold values derived
      from a literature review. RESULTS: The marginal cost-effectiveness of HACE
      compared with palliative care, given survival benefits of 3, 6, and 12 months,
      was $82,385, $41,193, and $21,045 per life-year (LY) gained, respectively. Cost
      effectiveness thresholds of $20,000 (strict), $50,000 (moderate), and $100,000
      (generous) per LY gained required survival benefits of 12.63, 4.94, and 2.47
      months, respectively, more than the expected baseline. CONCLUSION: The cost
      effectiveness of HACE for the treatment of CLM varies considerably according to
      the anticipated survival benefit. Results of future randomized controlled trials
      must demonstrate a survival benefit of nearly 5 months for HACE to meet the
      moderate cost-effectiveness standard of $50,000 per LY gained.

PMID- 10924577
TI  - Stent placement in ostial and nonostial atherosclerotic renal arterial stenoses:
      a prospective follow-up study.
AB  - PURPOSE: To compare the results of balloon percutaneous transluminal renal
      angioplasty (PTRA) and stent placement in atherosclerotic ostial, proximal, and
      isolated truncal stenoses. MATERIALS AND METHODS: Between January 1994 and April
      1998 the authors prospectively followed up 163 consecutive patients with 200
      atherosclerotic renal arterial lesions after primary PTRA or primary stent
      placement. Duplex ultrasonography was performed 1 day and 3, 6, and 12 months
      later. RESULTS: The primary 12-month PTRA patency rates were 34% (21 of 33
      atherosclerotic lesions) for ostial stenoses, 65% (20 of 60) for proximal
      stenoses, and 83% (five of 30) for truncal stenoses (chi(2) value, 15.63; P
      <.001). The corresponding stent patency rates were 80% (four of 21), 72% (nine of
      34), and 66% (five of nine), respectively (chi(2) value, 4.11; not significant).
      Significant stent-related reduction in risk of restenosis was limited to the
      ostial stenoses (P =.002). CONCLUSION: Renal arterial stent placement
      considerably improves patency in ostial stenoses, but compared with the
      technically successful PTRA, it does not significantly improve primary patency in
      proximal and isolated truncal renal arterial stenoses.

PMID- 10924576
TI  - Malignant colorectal obstruction treated by means of self-expanding metallic
      stents: effectiveness before surgery and in palliation.
AB  - PURPOSE: To determine the effectiveness and safety of metallic stents in the
      treatment of malignant colorectal obstruction before surgery and for palliation.
      MATERIALS AND METHODS: Eighty patients with acute malignant colorectal
      obstruction presumed to be malignant were treated by means of implanting self
      expanding metallic stents. RESULTS: Stent placement was successful in 70 of the
      80 patients and resolved bowel obstruction in 67 patients (96%). Two patients had
      colonic perforation and developed peritonitis 18 and 24 hours after stent
      placement; one patient died as a consequence. Thirty-three patients underwent
      elective surgery after 7 days +/- 3 (SD; range, 4-10 days), and adequate tumoral
      coverage and cleansing of the colon were observed in all patients. Stent
      placement was used as final palliative treatment in another 35 patients. Patient
      follow-up lasted a mean of 138 days +/- 93 (range, 36-334 days). The survival
      rate for the palliative group was 55% at 3 months, 44% at 6 months, and 25% at 9
      months. The estimated primary stent patency rate was 91% at 3 and 6 months.
      CONCLUSION: Management of colorectal obstruction by using metallic stents was
      effective and safe, although colonic perforation is a potential complication. In
      cases of palliation, the method may obviate palliative colostomy.

PMID- 10924578
TI  - Fine-needle percutaneous biopsy of renal masses with helical CT guidance.
AB  - PURPOSE: To evaluate the feasibility, accuracy, and clinical role of fine-needle
      percutaneous biopsy of renal masses, with helical computed tomographic (CT)
      guidance. MATERIALS AND METHODS: In 63 patients (mean age, 62 years), 73 biopsies
      were performed. The median tumor size was 4.0 cm. Tumor biopsy was performed with
      an 18-gauge needle by using helical CT guidance in an outpatient setting. Two to
      four cores per tumor were obtained. RESULTS: Biopsy material was insufficient for
      analysis in 15 (21%) procedures. The median tumor size of failed or successful
      biopsies was 3.0 or 4.8 cm, respectively (P =.03). A benign lesion was found at
      eight biopsies. Two samples were suspicious for renal cell carcinoma (RCC). RCC
      was found in 38 biopsy samples. The remainder were transitional cell carcinoma,
      metastasis, lymphoma, or sarcoma. Twenty-six patients underwent nephrectomy. The
      accuracies of biopsy for histopathologic and Fuhrman nuclear grade evaluation
      were 89% and 78%, respectively. For tumors of 3.0 cm or smaller or larger than
      3.0 cm, 37% (11 of 30) or 9% (four of 43) had failure of biopsy, respectively (P
      =.006). No substantial morbidity occurred. CONCLUSION: Fine-needle biopsy with
      helical CT guidance is accurate for the histopathologic evaluation of renal
      masses without morbidity. Indications are renal lesions that do not have the
      typical radiologic features of RCC, Bosniak category III or IV cystic lesions,
      and locally advanced or metastatic RCC.

PMID- 10924579
TI  - Multidirectional depiction of internal carotid arterial stenosis: three
      dimensional time-of-flight MR angiography versus rotational and conventional
      digital subtraction angiography.
AB  - PURPOSE: To evaluate whether and to what extent greater number of projection
      images obtained at three-dimensional (3D) time-of-flight (TOF) magnetic resonance
      (MR) angiography versus conventional digital subtraction angiography (DSA) causes
      overestimation of internal carotid arterial (ICA) stenosis. MATERIALS AND
      METHODS: DSA (two or three projections), rotational angiography (16 or 32
      projections), and 3D TOF MR angiography (12 projections) were performed in 47
      stenotic ICAs of 38 symptomatic patients. Two observers independently measured
      maximum stenosis, and the mean differences among MR angiography, DSA, and
      rotational angiography were compared. RESULTS: Three rotational and five MR
      angiograms were nondiagnostic. Seven MR angiograms of ICA stenoses showed a
      signal void and were excluded from analysis. On the remaining 32 angiograms, mean
      differences in maximum stenosis for observers 1 and 2, respectively, were 7% (95%
      CI: 3%, 12%) and 8% (95% CI: 3%, 13%) at MR angiography versus DSA and 2% (95%
      CI: -2%, 7%) and -1% (95% CI: -5%, 3%) at MR angiography versus rotational
      angiography. ICA stenosis was graded significantly higher at MR angiography
      versus DSA, whereas, it was not overestimated at MR angiography versus rotational
      angiography. The difference in maximum stenosis at MR angiography versus DSA was
      significantly different from that of MR angiography versus rotational
      angiography. CONCLUSION: Apparent overestimation of ICA stenosis at 3D TOF MR
      angiography versus conventional DSA may be partly explained by the greater number
      of projection images available at 3D TOF MR angiography.

PMID- 10924580
TI  - Usefulness of MR imaging-derived thermometry and dosimetry in determining the
      threshold for tissue damage induced by thermal surgery in rabbits.
AB  - PURPOSE: To investigate in vivo the feasibility of using magnetic resonance (MR)
      imaging-derived temperature and thermal dose measurements to find the threshold
      of thermal tissue damage. MATERIALS AND METHODS: Sonications were delivered in
      rabbit thigh muscles at varying powers. Temperature-sensitive MR images obtained
      during the sonications were used to estimate the temperature and thermal dose.
      The temperature, thermal dose, and applied power were then correlated to the
      occurrence of tissue damage observed on postsonication images. An eight-element
      phased-array transducer was used to produce spatially flat temperature profiles
      that allowed for averaging to reduce the effects of noise and the voxel size.
      RESULTS: The occurrence of tissue damage correlated well with the MR imaging
      derived temperature and thermal dose measurements but not with the applied power.
      Tissue damage occurred at all locations with temperatures greater than 50.4
      degrees C and thermal doses greater than 31.2 equivalent minutes at 43.0 degrees
      C. No tissue damage occurred when these values were less than 47.2 degrees C and
      4.3 equivalent minutes. CONCLUSION: MR imaging thermometry and dosimetry provide
      an index to predict the threshold for tissue damage in vivo. This index offers
      improved online control over minimally invasive thermal treatments and should
      allow for more accurate target volume coagulation.

PMID- 10924581
TI  - Normal and infarcted myocardium: differentiation with cellular uptake of
      manganese at MR imaging in a rat model.
AB  - PURPOSE: To assess whether normal myocardium can be distinguished from infarction
      at magnetic resonance (MR) imaging with low doses of manganese dipyridoxyl
      diphosphate (Mn-DPDP). MATERIALS AND METHODS: After 1-hour coronary arterial
      occlusion and 2-hour reperfusion, three groups of eight rats each were injected
      with 25, 50, or 100 micromol of Mn-DPDP per kilogram of body weight. The
      longitudinal relaxation rate (R1) in normal myocardium, reperfused infarction,
      and blood was repeatedly measured at inversion-recovery echo-planar imaging
      before and for 1 hour after the administration of contrast material. Afterward,
      several animals from each group were examined at high-spatial-resolution
      inversion-recovery spin-echo (SE) MR imaging. RESULTS: Manganese accumulated in
      normal myocardium but was cleared from reperfused infarction and blood. One hour
      after the administration of Mn-DPDP, R1 in normal myocardium (1.53 sec(-1) +/-
      0.03, 1.73 sec(-1) +/- 0.03, and 1.94 sec(-1) +/- 0.02, respectively, for 25, 50,
      and 100 micromol/kg) was significantly (P <.05) faster than that of reperfused
      infarction (0.99 sec(-1) +/- 0.03, 1.11 sec(-1) +/- 0.03, and 1.48 sec(-1) +/-
      0.06). Normal myocardium appeared hyperintense on T1-weighted inversion-recovery
      SE MR images and was clearly distinguishable from reperfused infarction.
      CONCLUSION: Mn-DPDP-enhanced inversion-recovery echo-planar and SE MR images
      demonstrated retention of manganese in normal myocardium and clearance of
      manganese from infarction. Mn-DPDP has characteristics similar to those of widely
      used thallium and may be useful in the assessment of myocardial viability at MR
      imaging.

PMID- 10924582
TI  - Hyperoxia-induced diffuse alveolar damage in pigs: correlation between thin
      section CT and histopathologic findings.
AB  - PURPOSE: To determine whether lung abnormalities at thin-section computed
      tomography (CT) in experimental hyperoxic lung injury correlate with the
      pathologic phases of diffuse alveolar damage (DAD). MATERIALS AND METHODS:
      Eighteen juvenile pigs were exposed to more than 80% oxygen-for 24, 48, 72, 96,
      or 120 hours-or room air in sealed cages. Their removed lungs were inflated with
      air infused through the trachea and examined with thin-section CT. Two
      independent observers, without knowledge of the exposure times, compared 63 areas
      selected on the CT scans with the corresponding pathologic and histologic
      findings, which were evaluated independently by two pathologists. RESULTS: CT
      findings correlated well with histologic findings (rho = 0.86, P <.001), which
      corresponded to the pathologic phases of DAD. All areas of normal CT attenuation,
      eight of nine spared regions within areas of opacity, and two of 15 areas of
      ground-glass opacity corresponded to the early exudative pathologic phase of DAD.
      All areas that showed traction bronchiolectasis at CT corresponded to the early
      proliferative pathologic phase. There was good observer agreement regarding the
      interpretation of CT findings (kappa statistic, >0.60) and histologic results
      (>/=0.70). CONCLUSION: Thin-section CT findings reflect the pathologic phases of
      DAD, although the early exudative phase cannot be specifically depicted by thin
      section CT. Traction bronchiolectasis on a CT scan suggests progression to the
      proliferative phase.

PMID- 10924583
TI  - Origin of metallic particles resembling microcalcifications on mammograms after
      use of abrasive cautery-tip cleaning pads during breast surgery: experimental
      demonstration.
AB  - PURPOSE: To determine if the act of cleaning a cautery tip with an abrasive pad
      dislodges radiopaque particles that can be transferred to breast tissue during
      surgery, thereby mimicking microcalcifications at mammography. MATERIALS AND
      METHODS: Mock breast surgery was performed by cauterizing bovine liver or fresh,
      normal, human breast tissue. The cautery tip was rubbed against a cleaning pad
      five to 20 times in the manner used intraoperatively and was touched on separate
      breast tissue specimens two to six times. Specimen radiography was then
      performed. Thirty-six breast specimens were used in three experiments, including
      28 used for the experimental conditions and eight control specimens. RESULTS:
      Particles collected from the cleaning pads resembled microcalcifications. After
      cauterization of liver, breast tissue, or both, in series, particles transferred
      from the cautery tip to breast tissue specimens could be identified on specimen
      radiographs. Transfer of particles after cautery of breast tissue occurred with
      increased numbers of rubs and specimen contacts. CONCLUSION: Radiopaque aluminum
      oxide particles from abrasive cautery-tip cleaning pads can be dislodged and
      transferred to breast tissue during surgery. Scrutiny of high-detail, spot
      compression, magnification mammograms will help identify these particles. Simple
      measures to mitigate particle transfer during breast surgery can prevent this
      problem and obviate a potential second procedure to remove particles mistaken for
      microcalcifications.

PMID- 10924584
TI  - Breast lesions: evaluation with dynamic contrast-enhanced T1-weighted MR imaging
      and with T2*-weighted first-pass perfusion MR imaging.
AB  - PURPOSE: To evaluate the diagnostic value of an imaging protocol that combines
      dynamic contrast-enhanced T1-weighted magnetic resonance (MR) imaging and T2*
      weighted first-pass perfusion imaging in patients with breast tumors and to
      determine if T2*-weighted imaging can provide additional diagnostic information
      to that obtained with T1-weighted imaging. MATERIALS AND METHODS: One hundred
      thirty patients with breast tumors underwent MR imaging with dynamic contrast
      enhanced T1-weighted imaging of the entire breast, which was followed immediately
      with single-section, T2*-weighted imaging of the tumor. RESULTS: With T2*
      weighted perfusion imaging, 57 of 72 carcinomas but only four of 58 benign
      lesions had a signal intensity loss of 20% or more during the first pass, for a
      sensitivity of 79% and a specificity of 93%. With dynamic contrast-enhanced T1
      weighted imaging, 64 carcinomas and 19 benign lesions showed a signal intensity
      increase of 90% or more in the first image obtained after the administration of
      contrast material, for a sensitivity of 89% and a specificity of 67%. CONCLUSION:
      T2*-weighted first-pass perfusion imaging can help differentiate between benign
      and malignant breast lesions with a high level of specificity. The combination of
      T1-weighted and T2*-weighted imaging is feasible in a single patient examination
      and may improve breast MR imaging.

PMID- 10924585
TI  - Gadopentetate dimeglumine excretion into human breast milk during lactation.
AB  - PURPOSE: To analyze the amount of gadopentetate dimeglumine excreted into human
      breast milk following intravenous injection of a clinical dose. MATERIALS AND
      METHODS: Gadopentetate dimeglumine was injected intravenously in 20 lactating
      women (23-38 years of age). Breast-feeding was interrupted for at least 24 hours.
      Serial samples of expressed milk were collected and analyzed for gadolinium
      concentration by means of inductively coupled plasma atomic emission spectrometry
      at a wavelength of 342.247 nm. RESULTS: The cumulative amount of gadolinium
      excreted in human breast milk during 24 hours was 0.57 micromol +/- 0.71 (SD;
      range, 0.05-3.0 micromol). The excreted dose was thus less than 0.04% of the
      administered intravenous dose (range, 0.001%-0.04%; mean, 0.009% +/- 0.010) for
      all cases. CONCLUSION: Less than 0.04% of administered gadopentetate dimeglumine
      is excreted into human breast milk. The amount transferred to a nursing infant
      orally would be far more than 100 times less than the permitted intravenous dose
      (200 micromol per kilogram of body weight) for neonates. The recommendation of a
      24-hour suspension of breast-feeding for lactating women should thus be
      reconsidered.

PMID- 10924586
TI  - Human skeletal muscle: sodium MR imaging and quantification-potential
      applications in exercise and disease.
AB  - PURPOSE: To use sodium 23 magnetic resonance (MR) imaging to quantify
      noninvasively total sodium in human muscle and to apply the technique in exercise
      and musculoskeletal disease. MATERIALS AND METHODS: Total [Na] sodium was
      determined from the ratio of the relaxation-corrected (23)Na signal intensities
      measured from short echo-time (0.4 msec) (23)Na images to those from an external
      saline solution reference. The method was validated with the blinded use of
      saline solutions of varying sodium concentrations. [Na] was measured in the calf
      muscles in 10 healthy volunteers. (23)Na MR imaging also was performed in two
      healthy subjects after exercise, two patients with myotonic dystrophy, and two
      patients with osteoarthritis. RESULTS: (23)Na MR imaging yielded a total [Na]
      value of 28.4 mmol/kg of wet weight +/- 3.6 (SD) in normal muscle, consistent
      with prior biopsy data. Spatial resolution was 0.22 mL, with signal-to-noise
      ratio of 10-15. Mean signal intensity elevations were 16% and 22% after exercise
      and 47% and 70% in dystrophic muscles compared with those at normal resting
      levels. In osteoarthritis, mean signal intensity reductions were 36% and 15%
      compared with those in unaffected knee joints. CONCLUSION: (23)Na MR imaging can
      be used to quantify total [Na] in human muscle. The technique may facilitate
      understanding of the role of the sodium-potassium pump and perfusion in normal
      and diseased muscle.

PMID- 10924587
TI  - Early-stage rheumatoid arthritis: prospective study of the effectiveness of MR
      imaging for diagnosis.
AB  - PURPOSE: To assess the effectiveness of magnetic resonance (MR) imaging for the
      diagnosis of early-stage rheumatoid arthritis (RA). MATERIALS AND METHODS: Fifty
      subjects (nine men and 41 women) with polyarthralgia who were suspected of having
      early-stage RA on the basis of clinical and radiographic findings were selected
      to undergo gadolinium-enhanced MR imaging of the hands. The MR imaging criterion
      for the diagnosis of early RA was bilateral enhancement in both wrists and/or the
      metacarpophalangeal and/or proximal interphalangeal joints. Follow-up continued
      until a final diagnosis was determined. Two patients left the study before the
      end of follow-up. RESULTS: Final diagnoses were established after a mean follow
      up of 776 days: rheumatoid arthritis in 26 patients and nonrheumatoid disease in
      22. Use of the MR imaging criterion yielded the correct diagnosis in 25 patients
      with RA and three false-positive results in three patients without RA. As
      compared with the traditional format and classification tree criteria of the
      American Rheumatism Association, the MR imaging criterion allowed detection of
      seven and six additional patients with true RA, respectively. CONCLUSION: The
      introduction of MR imaging into the diagnostic criteria for early RA may
      contribute to more accurate diagnosis in patients suspected of having RA and thus
      allow an earlier decision to start proper medication.

PMID- 10924588
TI  - Acetabular labrum: abnormal findings at MR imaging in asymptomatic hips.
AB  - PURPOSE: To determine the prevalence of abnormalities of the acetabular labrum in
      asymptomatic hips by means of magnetic resonance (MR) imaging and to correlate
      such abnormalities with age and the portion of the labrum. MATERIALS AND METHODS:
      MR imaging was performed in 71 asymptomatic hips that were radially sectioned
      perpendicular to the acetabular labrum at 30 degrees intervals. RESULTS: The
      shape of the labrum was triangular in 80% (304 of 382) of the labral segments,
      round in 13% (49 of 382), irregular in 7% (27 of 382), and not identified in 1%
      (two of 382). A homogeneous low signal intensity was observed in 56% (212 of
      382). The frequencies of labral irregularity or its absence and of high signal
      intensity increased both with subject age and with a more anterior anatomic
      labral location. CONCLUSION: In asymptomatic hips, abnormal findings regarding
      the shape and signal intensity of the acetabular labrum can be detected by means
      of MR imaging. The fact that the findings vary according to age and labral
      portion should be considered in interpreting MR images in patients suspected of
      having a labral lesion.

PMID- 10924589
TI  - Patellar instability: assessment on MR images by measuring the lateral trochlear
      inclination-initial experience.
AB  - Lateral trochlear inclination (LTI) of the knee was compared on magnetic
      resonance (MR) images obtained in 30 patients with patellar instability (PI) and
      30 patients with nonspecific internal knee derangement. Differences in LTI values
      between the two populations were significant (P <.001). Reproducibility of the
      measurement was judged excellent with an intraclass correlation superior to 0.98.
      Below a threshold value fixed at 11 degrees, LTI appears to be an excellent
      diagnostic test of PI with a sensitivity of 0.93 (28/30), a specificity of 0.87
      (26/30), and an accuracy of 0.90 (54/60).

PMID- 10924590
TI  - Bone mineral measurement of phalanges: comparison of radiographic absorptiometry
      and area dual X-ray absorptiometry.
AB  - With a standard, image-intensifier-based, digital radiographic system, high
      spatial-resolution images of the hand were acquired for analysis of phalangeal
      bone mineral density with dual x-ray absorptiometry (DXA). Results with
      phalangeal DXA had precision of plus or minus 0.67% and accuracy of 4.1% and
      correlated well with those with radiographic absorptiometry. This phalangeal DXA
      technique is potentially useful for clinical diagnosis of osteoporosis.

PMID- 10924591
TI  - Liver lesions: intermittent second-harmonic gray-scale US can increase
      conspicuity with microbubble contrast material-early experience.
AB  - The authors investigated the effect of intermittent second-harmonic gray-scale
      (ISHGS) ultrasonography (US) with SH U 508A microbubbles on the conspicuity of
      focal liver lesions. Twenty-three patients were included in the study. Images
      were analyzed subjectively and quantitatively. Objective lesion conspicuity was
      increased. In 12 of the 15 patients with liver malignancy, gray-scale defects
      were seen in previously unsuspected areas. ISHGS US may improve the sensitivity
      of US for liver lesions.

PMID- 10924592
TI  - Left ventricular mass and volume: fast calculation with guide-point modeling on
      MR images.
AB  - The authors describe a fast method for calculating left ventricle (LV) mass and
      volumes from multiplanar magnetic resonance (MR) images. Mathematic models were
      fitted to a small number of user-selected guide points in 15 healthy volunteers,
      13 patients after myocardial infarction, and a canine model of mitral
      regurgitation in eight dogs. Errors between model and manual contours were small
      (LV mass, 1.8 g +/- 4.9 [mean +/- SD]; end-diastolic volume, 2.2 mL +/- 4.6; end
      systolic volume, 2.3 mL +/- 3.8). Estimates of global function could be obtained
      in 6 minutes, a time saving of 5-10 times over estimates with manual contouring.

PMID- 10924593
TI  - Rapid three-dimensional MR imaging method for tracking a bolus of contrast agent
      through the brain.
AB  - A gradient-echo three-dimensional magnetic resonance imaging technique
      (principles of echo shifting with a train of observations, or PRESTO) is
      presented for use in tracking a bolus of paramagnetic contrast agent through the
      brain. The approach combines a segmented echo-planar type of acquisition with
      echo shifting, which leads to echo times that are longer than the repetition
      time. Unlike echo-planar imaging, the method maintains image resolution despite
      drastic T2* changes and frequency shifts.

PMID- 10924594
TI  - The low false-negative rate for stereotactic breast biopsy.

PMID- 10924595
TI  - Gadolinium-enhanced MR imaging in the differential diagnosis of placenta accreta
      and placenta percreta.

PMID- 10924597
TI  - In memoriam

PMID- 10924596
TI  - CT of acute cerebral ischemia.

PMID- 10924598
TI  - In memoriam

PMID- 10924599
TI  - Abstracts of current literature

PMID- 10924600
TI  - A new step forward with TRANSFUSION online

PMID- 10924601
TI  - Nonmyeloablative HPC transplantation.

PMID- 10924602
TI  - Assessment of donor T-cell function in cellular blood components by the CD69
      induction assay: effects of storage, gamma radiation, and photochemical
      treatment.
AB  - BACKGROUND: Functional donor T-lymphocytes in blood components may cause a
      variety of transfusion complications. A flow cytometric assay based on the
      measurement of induced CD69 expression may be an alternative to cell
      proliferation methods in determining the functional status of these cells in
      blood components. STUDY DESIGN AND METHODS: Seven units of whole blood, RBCs, and
      platelet concentrates (PCs) were stored under blood bank conditions. Half of 3
      PCs each were gamma-radiated or treated with UVA+psoralen; the other half served
      as controls. Samples were analyzed for phorbolester-induced expression of CD69 as
      an indicator of cell responsiveness and for exclusion of propidium iodide as a
      measure of cell membrane integrity and viability. RESULTS: CD69 inducibility and
      propidium iodide exclusion decreased exponentially (half-life, 3. 3 and 8.1 days,
      respectively) during cold blood storage. Irradiation and UVA+psoralen treatment
      of PCs immediately reduced CD69 inducibility to 21 percent (controls, 82%; p =
      0.004) and 12 percent (controls, 95%; p = 0.0008), respectively. The proportion
      of cells capable of propidium iodide exclusion was similar in treated samples and
      controls, but it declined faster in the treated samples during subsequent
      storage. CONCLUSION: Flow cytometric measurement of CD69 induction can be adapted
      to provide quantitative assessment of T-cell function in blood components.
      Results obtained by the CD69 assay are in general agreement with those previously
      reported by use of proliferation methods; the assay may be useful for special
      applications in transfusion medicine.

PMID- 10924603
TI  - WBC subset analysis of WBC-reduced platelet components.
AB  - BACKGROUND: WBC-reduced platelet components may be prepared by filtration or
      apheresis processing. Both methods have previously been shown to result in a
      residual total WBC content <5 x 10(6) per component. However, there may be
      differences in the efficacy of these techniques for removing certain WBC subsets.
      STUDY DESIGN AND METHODS: Two multiparameter flow cytometric assays were
      developed and validated to perform WBC analysis on WBC-reduced platelets
      collected with two apheresis instruments (Amicus and COBE Spectra) and on 6 units
      of filtered pooled random-donor platelet concentrates. RESULTS: All components
      contained <1 x 10(5) WBCs. The COBE Spectra and Amicus apheresis platelet
      components contained more WBCs than did filtered pooled platelets (p<0.05).
      Lymphocytes (T and B), monocytes, and granulocytes were identified in all
      components. Granulocyte content was lowest in the Amicus components and filtered
      pools. Monocytes were lowest in filtered pools. Amicus platelet components had
      fewer granulocytes and monocytes than the COBE Spectra platelets. Amicus and COBE
      Spectra components contained more lymphocytes than the filtered pools.
      CONCLUSION: Multiparameter flow cytometry can be used to quantify and
      characterize WBCs in WBC-reduced platelet components. WBC reduction by filtration
      or apheresis was highly effective. WBCs from each subset were identified in all
      components. Although filtered pools had the lowest numbers of WBCs, the very low
      numbers observed in all components suggests that the absolute quantitative
      differences in WBC subset content are of questionable clinical significance.

PMID- 10924604
TI  - Evaluation of pooled platelet concentrates using prestorage versus poststorage
      WBC reduction: impact of filtration timing.
AB  - BACKGROUND: Concern for the undesirable consequences of transfusing passenger
      WBCs is leading to the general use of WBC-reduced platelet concentrates (PCs).
      However, the impact of prestorage versus poststorage WBC reduction on the quality
      of platelet products has not been clearly defined. STUDY DESIGN AND METHODS:
      Pooled PCs were WBC reduced before or after 5-day storage, by use of a WBC filter
      (PXL-8, Pall Corp.). Samples from pools were taken on days 1 and 5, before and
      after filtration, and on Day 9 of storage and assessed for cell counts,
      biochemical values, expression of platelet glycoproteins, thrombin generation,
      and content of IL-6, IL-8, TNFalpha, transforming growth factor beta1 (TGFbeta1),
      and anaphylatoxins C3a and C4a. RESULTS: Filtration of fresh and 5-day-stored
      pooled PCs via a PXL-8 filter was similarly efficient, rendering pools with low
      WBC counts (<1 x 10(6) cells) and high platelet recovery (>95%). No major changes
      were found in the metabolic behavior or the expression of platelet GPIb,
      GPIIb/IIIa, CD62, and CD63 in PCs filtered before or after storage. Filtration,
      either before or after storage, increased by less than 5 percent the proportion
      of CD62+ platelets. Moreover, no changes were found in the concentration of
      prothrombin fragments 1 and 2 and thrombin-antithrombin complexes in the pooled
      PCs derived from the time of filtration. Finally, prestorage WBC reduction
      abrogated the accumulation of IL-6 and IL-8, but it did not prevent that of
      anaphylatoxins C3a and C4a nor of TGFbeta1. However, filtration through a PXL-8
      filter significantly reduced (40-90%) the amount of IL-8, C3a, and C4a in the
      filtrate. CONCLUSIONS: The timing of PXL-8 filtration of PCs has little impact on
      the efficiency of WBC reduction and on platelet recovery, and it does not seem to
      affect the quality of platelets or the generation of thrombin in the PCs. As
      regards the goal of reducing the amount of bioactive products in PCs, it remains
      uncertain as to whether prestorage WBC reduction fully eliminates the need for
      poststorage filtration. Prestorage filtration leads to low levels of IL-6 and IL
      8 in PCs, but it does not impair the poststorage content of TGFbeta1 or anaphyla
      toxins. By contrast, poststorage PXL-8 filtration removes significant amounts of
      C3a and C4a, and thus it might provide clinical benefits beyond those of
      prestorage WBC reduction.

PMID- 10924606
TI  - A comparison of prestorage WBC-reduced whole-blood-derived platelets and bedside
      filtered whole-blood-derived platelets in autologous progenitor cell transplant.
AB  - BACKGROUND: Prestorage WBC-reduced platelet concentrates (PCs) can be
      manufactured from platelet-rich plasma (PRP) by in-line filtration of PRP. There
      are few published data on the clinical use of these products, as compared to
      bedside-filtered pools of standard PCs (S-PCs) manufactured from PRP. STUDY
      DESIGN AND METHODS: A prospective, randomized trial was conducted in autologous
      progenitor cell transplant patients requiring platelet transfusions with each
      patient as his or her own control who was given a pool of 5 units of WBC-reduced
      PCs and a pool of 6 units of S-PCs within a 3-hour period. The pools were
      characterized before transfusion for platelet and WBC content, P-selectin
      expression, and IL-8. The patients were monitored with platelet counts and vital
      signs and observed for reactions. Data were analyzed using Mann-Whitney U tests.
      RESULTS: Thirty-three transfusions were administered to 13 patients. Median
      platelet content in the WBC-reduced PC pools was lower than that in the S-PC
      pools (3.3 vs. 4.0 x 10(11), p<0.01). Median WBC content was 4 to 5 log less in
      the WBC-reduced PC pools (2.5 x 10(4) vs. 4.6 x 10(8), p<0.01). Median IL-8
      levels (pg/mL) were lower in the WBC-reduced PC pools (2 vs. 36, p<0.01). No
      differences were observed in CCI, but the median absolute increase after
      transfusion of the S-PC pools was higher (25 vs. 19 x 10(9)/L, p<0.01), which
      reflected the larger size of the S-PC pools. No overall differences in vital
      signs were recorded. Two reactions were observed, both in temporal association
      with the transfusion of pools of S-PCs. CONCLUSIONS: A pool consisting of 5 units
      of WBC-reduced PCs gave a median platelet increment of 19 x 10(9) per L in these
      thrombocytopenic patients and has a median WBC content 1 to 2 log below the
      accepted threshold for primary alloimmunization or CMV transmission.

PMID- 10924605
TI  - Comparison of plateletpheresis concentrates produced with Spectra LRS version 5.1
      and LRS Turbo version 7.0 cell separators.
AB  - BACKGROUND: The importance of transfusing WBC-reduced blood components is widely
      recognized, as it reduces the risk of alloimmunization and transfusion
      transmitted CMV infections. The latest generation of cell separators allows the
      collection of WBC-reduced apheresis platelet concentrates (APCs). MATERIALS AND
      METHODS: Consecutive APCs (n = 232) were retrospectively evaluated: 163 collected
      with the Spectra LRS [leukocyte-reduction system] Version 5.1 (Group A) and 69
      with the LRS Turbo Version 7.0 (Group B) (both: COBE BCT). Donor peripheral blood
      count, procedure data, platelet yield, collection efficiency (CE), and residual
      WBC count in APCs were recorded. RESULTS: The platelet yield was higher in Group
      B than in Group A: 5.5 +/- 1.4 versus 4.4 +/- 1.1, p<0.0001; residual WBCs were
      <5 x 10(6) in 99.4 percent of Group A APCs and in 97.1 percent of Group B APCs.
      CE was higher in Group B than in Group A: 51.4 +/- 8.7 versus 43.6 +/- 6.3,
      p<0.0001. Moreover, a correlation between predonation platelet count and platelet
      yield was observed in both groups. A double product (platelet yield >6.0 x
      10(11)) was obtained in 28.9 percent of Group B APCs and in 9.2 percent of Group
      A APCs. CONCLUSIONS: The Spectra LRS Turbo version 7.0 release showed a better CE
      and resulted in a higher platelet harvest than did the LRS version 5.1. High
      predonation platelet counts allow a higher platelet yield.

PMID- 10924607
TI  - RBC T activation and hemolysis: implications for pediatric transfusion
      management.

PMID- 10924608
TI  - Analysis of the turin umbilical cord blood bank registry.
AB  - BACKGROUND: The polymorphic nature of the HLA system reduces a patient's
      probability of finding an HLA-compatible unrelated bone marrow (BM) donor, even
      though more than 6 million individuals are enrolled in international registries.
      Recently, umbilical cord blood (UCB) has been successfully employed as a source
      of HPCs. The use of such cells reduces the risk of GVHD and allows transplants
      with one or two HLA mismatches. UCB represents an expensive resource: therefore,
      it is necessary to carefully manage the UCB unit inventory. STUDY DESIGN AND
      METHODS: The current study analyzed the genetic heterogeneity of HLA-A, -B, and 
      DR gene frequencies between pools of UCB and unrelated-donor BM in the Piedmont
      (an administrative region of Italy). An Italian hematology patient's probability
      of finding complete or partial matches as a function of donor pool size was
      determined by considering subsamples randomly selected from the local unrelated
      BM donors. RESULTS: The HLA gene frequencies in UCB and unrelated-donor BM pools
      were not significantly different. The search simulation, based on actual HLA
      phenotypes, showed that the percentage of Italian patients matched with an HPC
      unit increases remarkably if 1 or 2 mismatches are accepted, reaching a
      proportion of 90 percent with an inventory of only about 500 units, while the
      increment is not so remarkable if the number of UCB units is greater. CONCLUSION:
      To optimize economic resources and to be internationally competitive, UCB banks
      should aim to increase the genetic heterogeneity of their units rather than
      increasing the UCB inventory, acquire efficient quality control systems, and
      acquire and preserve UCB units with a greater number of nucleated cells.

PMID- 10924609
TI  - Preterm birth and the availability of cord blood for HPC transplantation.
AB  - BACKGROUND: Cord blood from deliveries at term can be used for HPC
      transplantation. The objective of this study was to determine the amounts of cord
      blood nucleated cells (NCs) and HPCs that were collectable from preterm
      deliveries. STUDY DESIGN AND METHODS: Cord blood collected from preterm
      deliveries between 22 and 36 weeks of gestation was compared with regard to
      volume, NC count (/mL), CD34+ cell count (/mL), and the NC and CD34+ cell counts
      per cord blood sample and at different gestational ages. RESULTS: A correlation
      was found between gestational age and NC count (r = 0.52, p<0.001), and an
      inverse relation was found between gestational age and CD34+ cell count (r = -
      0.68, p<0.001). The CD34+ cell count per cord blood sample was independent of
      gestational age (r = - 0.13, p = NS), and no significant difference between early
      (22-32 week) and late (33-36 week) preterm deliveries was found (p = 0.870).
      Comparison with published data from cord blood transplantations revealed that up
      to one-third of preterm samples contained at least as many NCs (or CD34+ cells)
      as the median cell dose transplanted (calculated for the median recipient weight)
      in the respective study. Furthermore, 77 percent of all preterm samples contained
      at least 1 x 10(7) NCs (and 42% at least 1 x 10(5) CD34+ cells) per kg for
      transplantation in a recipient of 20-kg body weight, which corresponds to the
      lower threshold of cells per kg in the graft recommended by Eurocord. CONCLUSION:
      Preterm delivery should not be a reason to exclude cord blood collection if
      allogeneic cord blood transplantation in a sibling is planned.

PMID- 10924610
TI  - Immunologic changes after transfusion of autologous or allogeneic buffy coat-poor
      versus WBC-reduced blood transfusions in patients undergoing arthroplasty. II.
      Activation of T cells, macrophages, and cell-mediated lympholysis.
AB  - BACKGROUND: To estimate the impact of RBC preparations on the status of
      postoperative immune activation, the soluble cytokine receptors of TNFalpha (sTNF
      R) and IL-2 (sIL-2R), as well as neopterin and cell-mediated lympholysis (CML),
      were measured. STUDY DESIGN AND METHODS: Patients undergoing strictly
      standardized anesthesiologic management for elective orthopedic surgery were
      enrolled in a prospective study. The perioperative course (Days 0, 3, 7, and 10)
      of sTNF-R, sIL-2R, neopterin, and CML was compared after random assignment to
      allogeneic buffy coat-reduced (Group 2, n = 8) or WBC-reduced (Group 3, n = 11)
      RBC transfusion regimen. Recipients of autologous buffy coat-reduced RBC
      transfusions (Group 1, n = 15) served as controls. Patients receiving
      intraoperatively and postoperatively salvaged blood only (n = 10) were separately
      analyzed as Group 4. RESULTS: In Group 1, a short-lasting increase in soluble
      cytokine receptors, a diminished cytolytic response (Day 0 vs. Day 7: sTNF-R, p =
      0.0001; sIL-2R, p = 0.0004; CML, p = 0. 0238), and an elevation of neopterin (Day
      0 vs. Day 3: p = 0.0064) were observed. In contrast, in allogeneically transfused
      patients, sTNF-R (Group 2, p = 0.0469: Group 3, p = 0.0039), sIL-2R (Group 3, p =
      0.002) and neopterin (Group 3, p = 0.0164) increased further from baseline to Day
      10 (Day 0 vs. Day 10), and this increase was accompanied by a diminished
      cytolytic response (Day 0 vs. Day 10: Group 2, p = 0.05; Group 3, p = 0.0076).
      Patients in Group 4 showed a short-lasting increase in sIL-2R (Day 0 vs. Day 3: p
      = 0.0078), neopterin (Day 0 vs. Day 3: p = 0.0156) and sTNF-R (Day 0 vs. Day 7: p
      = 0.0781). CONCLUSION: Allogeneic transfusions seem to prolong the postoperative
      status of immune activation, even when WBC-filtered RBCs are used for the
      transfusion regimen.

PMID- 10924611
TI  - An acute hemolytic transfusion reaction due to anti-IH in a patient with sickle
      cell disease.
AB  - BACKGROUND: A hemolytic transfusion reaction (HTR) due to anti-IH is reported in
      a patient with sickle cell disease (SCD). CASE REPORT: An 18-year-old woman with
      SCD and a complete phenotype on file had been identified as group B-positive with
      negative antibody-screening tests and had received 1 unit of packed RBCs. Ten
      days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL.
      Antibody-screening tests and panel cells were positive at all test phases with a
      negative autocontrol, which suggested alloantibodies. Phenotypically matched
      group O RBCs were issued emergently. After the transfusion of 100 mL, the patient
      had an HTR with chills, fever, and tachycardia and laboratory findings of
      hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with
      a high thermal amplitude (reactive with group O, but not group B RBCs at 37
      degrees C) was identified. Autologous RBCs appeared to have normal I antigen
      expression, but less H antigen than pooled group B RBCs. She was given group B
      RBCs, uneventfully, by use of a blood warmer. CONCLUSIONS: This is a rare case of
      anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD,
      and as an autoantibody that may mimic an alloantibody. Ironically, this HTR
      resulted from the effort to provide phenotypically matched RBCs, which
      necessitated the selection of group O RBCs.

PMID- 10924612
TI  - RBC transfusion and postoperative length of stay in the hospital or the intensive
      care unit among patients undergoing coronary artery bypass graft surgery: the
      effects of confounding factors.
AB  - BACKGROUND: Data on the independent association between perioperative allogeneic
      blood transfusion (ABT) and postoperative length of stay at the hospital or in
      the intensive care unit (ICU) are sparse. STUDY DESIGN AND METHODS: The records
      of 421 consecutive patients undergoing coronary artery bypass graft (CABG)
      operations at the Massachusetts General Hospital were reviewed. The effect of
      perioperative ABT in explaining the variation in the postoperative length of stay
      (LOS) at the hospital or in the ICU was calculated after adjustment for the
      effects of 20 confounding factors that pertained to severity of illness,
      difficulty of operation, and risk of postoperative wound infection or pneumonia.
      RESULTS: Postoperative LOS averaged (mean +/- SE) 8.0 +/- 0.3 days in the
      hospital and 50.0 +/- 4.1 hours in the ICU. After adjustment for the effects of
      confounding factors, the postoperative length of hospitalization increased by
      0.837 percent (95% CI, 0.249-1.425%) per RBC unit transfused (p<0.001), and the
      postoperative length of stay in the ICU increased by 0.873 percent (95% CI, 
      0.068-1.814%) per RBC unit transfused (p<0.10). CONCLUSION: Allogeneic blood
      transfusion was independently associated with longer postoperative stays in the
      hospital or the ICU, but the observed independent association is perhaps too
      small to be clinically relevant. This independent association may be due to a
      relationship between ABT and a higher incidence of septic complications of
      surgery, or it may reflect the function of blood transfusion as a surrogate
      marker for severity of illness.

PMID- 10924613
TI  - Determination of sibship by PCR-amplified short tandem repeat analysis in Taiwan.
AB  - BACKGROUND: Sibship determination for any two persons whose parents have died is
      one of the most fundamental issues of personal identification, second only to
      those of a parent-child relationship. STUDY DESIGN AND METHODS: By automated
      fluorescence analysis of a PCR-amplified short tandem repeat (STR) system in
      conjunction with capillary electrophoresis, a panel of up to 15 polymorphic,
      autosomal, unlinked STR loci was used to investigate sibship index (SI) values in
      a cohort of 126 true sibling pairs. These SI values were then compared with those
      of 126 random pairs. RESULTS: The 15-loci STR panel provides a cumulative power
      of exclusion of 0. 9999997. Of the 126 random pairs, 124 (98.4%) had cumulative
      sibship indices (CSIs) of <1.0, and none had a CSI of >3.0 (median, 0.0101;
      range, 0.0000003-2.5376). In contrast, 107 (85%) of the 126 sibling pairs had a
      CSI of >100 (median, 5,579.9853; range, 0.0747-9,406,829, 249.8461). However,
      five pairs (4%) of the sibling group had a CSI of <3.0. True sibship was
      confirmed for this particular group by additional paternity testing and
      mitochondrial DNA sequence analysis. Among a total of 1890 observations (15 loci
      x 126 pairs), two alleles per locus were shared 760 times (40.21%) (mean, 6.03
      loci; range, 1-10) in the sibling group, but only 192 times (10.16%) in the
      random group (mean, 1.52 loci; range, 1-5) (p<0.001). No alleles were shared 696
      times (36.83%) in the unrelated pairs, as compared to 176 times (9.31%) in the
      sibling group (p<0.001). A polarized distribution was not noted in the sharing of
      single alleles in either the random or the sibling group: 1002 observations
      (53.02%) and 954 observations (50.48%), respectively. CONCLUSION: Highly
      polymorphic STR analysis can be discriminative in most sibship determinations,
      and the sharing of two alleles per locus is most informative in indicating
      sibship. Complementary mitochondrial DNA sequence analysis is mandatory in a few
      cases to exclude or establish true sibship when CSIs are equivocal and neither
      parent is available.

PMID- 10924614
TI  - V(D)J germline gene repertoire analysis of monoclonal D antibodies and the
      implications for D epitope specificity.
AB  - BACKGROUND: The D antigen is a highly immunogenic human RBC antigen.
      Alloimmunization against the D antigen produces high-affinity antibodies that
      cause hemolytic transfusion reactions and HDN. STUDY DESIGN AND METHODS: Cloning
      and subsequent sequence analysis of 11 new samples of monoclonal anti-D was
      performed in an attempt to identify V(D)J germline gene usage. Sequences were
      compared and analyzed with 37 previously published samples of anti-D for
      identification of V(H) and V(L) pairings, canonical structures, and conformation
      of restricted germline gene usage. RESULTS: The V(H) and V(L) pairings used by
      the new D MoAbs resulted in seven canonical combinations, three of which had not
      been described previously. Preferential usage of gene segments from the VH3 and
      VH4 families and of D3, D6, JH6, and DPK9 germline gene segments was also
      determined. Three samples of anti-D from different donors were found to use
      similar V(H) and V(kappa) germline genes, despite the fact that two of the
      antibodies recognized epD6/7 and the third recognized epD1. From the cumulative
      analysis of the anti-D IgG, 24 V(H) and V(L) gene pairings were identified,
      resulting in only 10 canonical structures. CONCLUSIONS: Despite the potential for
      diversity, only a minority of V(H) and V(L) germline genes are used by anti-D.
      Consequently, V(H) and V(L) pairings and the resulting canonical structures are
      similarly restricted.

PMID- 10924615
TI  - Secretor genotyping for A385T, G428A, C571T, C628T, 685delTGG, G849A, and other
      mutations from a single PCR.
AB  - BACKGROUND: The secretor status of an individual is important for disease
      relationship studies, because it determines the presence of ABH blood group
      antigens in the gastrointestinal tract and bodily secretions. Routine serologic
      methods for determining secretor status are unreliable. Current strategies based
      on PCR for genotyping require relatively large amounts of DNA and have to be done
      as several separate experiments. STUDY DESIGN AND METHODS: A single, multiplex
      PCR technique followed by RFLP digestion with four restriction enzymes produced
      unique genotype profiles for most known secretor (FUT2) mutations. RESULTS:
      Samples from a range of individuals with common and rare secretor genotypes were
      analyzed. Each gave unique patterns that allowed secretor genotypes to be
      determined. CONCLUSION: By using the method described here and genomic DNA, a
      secretor genotype based on the FUT2 mutations A385T, G428A, C571T, C628T,
      685delTGG, and G849A could be accurately determined.

PMID- 10924616
TI  - Detection of HLA antibodies by using flow cytometry and latex beads coated with
      HLA antigens.
AB  - BACKGROUND: Detection of HLA class I antibodies in sera is needed in various
      clinical situations. The standard method for detecting HLA class I antibodies is
      the complement-dependent lymphocytotoxicity (CDC) assay, but solid-phase assays
      are now available. STUDY DESIGN AND METHODS: This study assessed the ability of a
      flow cytometric assay using latex beads coated with HLA class I antigens to
      detect HLA class I-specific antibodies. The CDC assay was compared with the
      pooled-bead assay for the detection of HLA class I antibodies. Thirty-one
      randomly selected serum samples previously tested by CDC assay were tested with
      pooled beads and analyzed by flow cytometry. Twenty-seven additional serum
      samples, chosen by clinical criteria and CDC assay results, were tested against
      the pooled beads. Next, samples from six patients from whom three or more serum
      samples were drawn on consecutive days were tested with both methods. Finally,
      serum samples that were proved positive by both methods were tested with selected
      beads coated with antigens from a single person. RESULTS: Among the randomly
      selected serum samples, there was 90-percent agreement between the two assays.
      There was 96-percent agreement between the two assays of the 27 samples that were
      selected by clinical criteria and CDC assay results. Testing the sera with
      individual beads suggested that the HLA class I antibodies react with beads
      expressing the corresponding HLA antigen and beads expressing antigens in the
      same cross-reactive group. CONCLUSION: The pooled-bead assay can be used as an
      alternative method for detecting HLA class I antibodies. However, if the
      specificity of the HLA class I antibody is required, another assay must be used.

PMID- 10924617
TI  - HCV RNA in blood donors with isolated reactivities by third-generation RIBA.
AB  - BACKGROUND: The objective of this collaborative study was to learn the proportion
      of HCV RNA-positive samples obtained from a population of donors with isolated
      anti-HCV reactivities by third-generation RIBA (RIBA-3) (indeterminate results).
      STUDY DESIGN AND METHODS: During a 2-year period, 11 blood transfusion centers
      kept all samples with indeterminate RIBA-3 results to test them by PCR, using
      both local and commercial techniques. RESULTS: Of the 758 RIBA-3 indeterminate
      samples, 10 (1.3%) were positive for HCV RNA: 3. 3 percent (6/180) and 1.3
      percent (4/317) of samples with anti-core or anti-NS3 reactivity, respectively,
      and none of the 52 and 209 samples with anti-NS4 or anti-NS5 reactivity,
      respectively. HCV RNA-positive donors with anti-core reactivity were infected
      with different subtypes (1 with HCV subtype 1b, 1 with 2, 1 with 2a/2c, 2 with
      3a, and 1 with 5a), and a follow-up indicated a chronic-carrier state in two of
      the six donors. Acute hepatitis was diagnosed in three of the four donors with
      anti-NS3 reactivity alone. Two of these three were IV drug users and were
      infected with subtype 1a. CONCLUSION: HCV RNA-positive donors with indeterminate
      results in RIBA-3 are extremely rare, but they do exist. They were observed only
      when either anti-core or anti-NS3 was present. With such a RIBA-3 profile, PCR
      testing remains necessary to reveal an eventual acute or chronic HCV infection.

PMID- 10924618
TI  - Evaluation of automated nucleic acid extraction devices for application in HCV
      NAT.
AB  - BACKGROUND: To further improve the safety of the blood supply, various national
      blood transfusion organizations presently use or are in the process of
      implementing routine HCV NAT in minipools. According to the Committee for
      Proprietary Medicinal Products (CPMP) of the European Union, the HCV NAT
      detection limit of the assay should be 100 IU per mL (270 geq/mL) for testing
      initial plasma pools. Paul Ehrlich Institute (PEI) regulations stipulate that
      5000 IU per mL (13,500 geq/mL) must be detected to calculate the amount
      contributed by individual donations composing the minipool. The sensitivity for
      HCV RNA extraction achieved by three commercially available laboratory kits was
      compared. STUDY DESIGN AND METHODS: Nucleic acids from 1-in-3 serial dilutions of
      an HCV RNA run control (Pelispy, CLB) were extracted with three kits (Cobas
      Amplicor, Roche Diagnostic Systems; BioRobot 9604, Qiagen; and NucliSens
      Extractor, Organon Teknika). HCV PCR of all extracts was performed using a second
      generation Cobas Amplicor HCV test and the Cobas Amplicor analyzer. RESULTS: The
      manual Cobas Amplicor, the BioRobot 9604, and the NucliSens Extractor setups
      allow a 95-percent HCV RNA detection limit of 129, 82, and 12 geq per mL,
      respectively. The maximal pool size for the manual Cobas Amplicor, the BioRobot
      9604, and the NucliSens Extractor kits that would still meet the PEI criteria for
      HCV NAT in minipools was calculated at 104, 164, and 1125 donations,
      respectively. CONCLUSION: All three HCV NAT kits evaluated meet the criteria set
      by CPMP and PEI. The highest sensitivity for HCV NAT screening can be achieved
      with the high-volume NucliSens Extractor method in combination with the Cobas
      Amplicor HCV v2.0 test on the Cobas Amplicor analyzer.

PMID- 10924619
TI  - GB virus type C/HGV markers in HCV RNA-positive French blood donors: correlation
      with HCV genotypes and risk factors.
AB  - BACKGROUND: Exposure to GB virus type C/HGV (GBV-C/HGV) could be determined by
      detection either of RNA by RT-PCR or of antibodies of the envelope protein E2.
      STUDY DESIGN AND METHODS: The aim of the study was to determine the proportion of
      the GBV-C/HGV markers of infection in a blood donor population infected with HCV
      and to identify GBV-C/HGV routes of transmission that are associated with HCV
      genotypes and risk factors. RESULTS: Among 306 HCV RNA-positive blood donors, the
      proportion of GBV-C/HGV RNA-positive donors and anti-E2-positive donors was 19.3
      percent (95% CI = 15.0-24.2%) and 42.1 percent (95% CI = 36.6-47.9%),
      respectively. Exposure to GBV-C/HGV (RNA or anti-E2) was significantly associated
      with the risk factor of IV drug use. There was a trend toward association with
      HCV subtypes 1a and 3a, probably because these HCV subtypes are the most frequent
      in IV drug users. No correlation was observed between ALT elevation and the
      presence of GBV-C/HGV RNA. CONCLUSION: In persons with HCV infection, IV drug use
      seems to be a major route of GBV-C/HGV transmission. Precautions taken to avoid
      HCV infection will probably also decrease GBV-C/HGV transmission.

PMID- 10924620
TI  - Human error-a significant cause of transfusion mortality.

PMID- 10924621
TI  - Efficacy of SD-treated plasma during liver transplantation.

PMID- 10924622
TI  - Screening of six racial groups for the intron 5 G-->A 3' splice acceptor mutation
      responsible for the polynesian kidd (a-b-) phenotype: the null mutation is not
      always associated with the JKB allele.

PMID- 10924623
TI  - Hysteroscopic endometrial ablation using free heated saline for the treatment of
      menorrhagia.
AB  - STUDY OBJECTIVE: To assess the safety and efficacy of hysteroscopic endometrial
      ablation using controlled intrauterine instillation and circulation of heated (90
      degrees C) saline. DESIGN: Phase II clinical study (Canadian Task Force
      classification II-2). SETTING: Preliminary study performed in an outpatient
      ambulatory surgery center of a university hospital. PATIENTS: Twenty women with
      menorrhagia of benign causes. INTERVENTION: Hysteroscopic endometrial ablation.
      MEASUREMENTS AND MAIN RESULTS: There were no complications. At no time did fluid
      leak from the fallopian tubes or cervix during treatment. Six patients had
      concurrent laparoscopy to measure serosal temperatures and to observe fimbriae
      directly during the 10-minute treatment. Serosal and endocervical temperatures
      were not elevated. Eighteen women kept evaluable menstrual diaries for 2 months
      before and 12 months after surgery. Ten women (55.6%) became amenorrheic, four
      (22.1%) hypomenorrheic, and three (16.7%) returned to normal periods after 12
      months of follow-up. One woman (5.6%) reported a 75% decrease in menstrual flow
      but continued to be menorrhagic by definition. One patient subsequently underwent
      hysterectomy for simple endometrial hyperplasia. CONCLUSION: This procedure
      appears to be a safe method of globally ablating the endometrium, resulting in
      effective treatment of menorrhagia.

PMID- 10924624
TI  - Laparoscopy in the "normal" infertile patient: a question revisited.
AB  - STUDY OBJECTIVE: To determine the prevalence of reproductive pathology in a group
      of infertile women thought to be at low risk for altered pelvic anatomy. DESIGN:
      Retrospective chart review and follow-up (Canadian Task Force classification II
      2). SETTING: Academic-affiliated, private reproductive endocrinology practice.
      PATIENTS: One hundred infertile women. INTERVENTION: Diagnostic and/or
      therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: Of 100 patients with a
      negative reproductive work-up up to the point of laparoscopy, 68 had pathology of
      reproductive significance: intrinsic tubal disease 24, peritubal adhesive disease
      34, and endometriosis 43, some in combination. Laparoscopy was especially helpful
      in establishing treatment protocols for older women, who were referred for
      assisted reproductive techniques earlier than otherwise might have been the case.
      Women conceived after hormone therapy and after operative intervention. Although
      the hysterosalpingogram was read as normal in all women, tubal disease was
      diagnosed laparoscopically, independent of endometriosis, in 27 patients, with 2
      having complete obstruction. Endometriosis stage I-II was found in 22 patients,
      stage III in 13, and stage IV in 6. CONCLUSION: Even in women thought to be at
      low risk for significant pelvic pathology affecting reproduction, the yield was
      high. Although some pregnancies were achieved after operative intervention,
      frequently laparoscopy was helpful in making a decision to go to assisted
      reproductive technology, particularly when infertility had been of long duration
      and in older women. Frequently the degree of pathology was such that a full
      operating suite was necessary to provide adequate instrumentation and anesthesia
      for operative intervention, which would not have been the case with office
      laparoscopy.

PMID- 10924625
TI  - Endometrial thermal balloon ablation with the ThermaChoice system: effect of
      intrauterine pressure and duration of treatment.
AB  - STUDY OBJECTIVE: To determine the safety and efficacy of thermal balloon therapy
      under variable intrauterine pressures and durations of treatment. DESIGN:
      Retrospective cohort study. (Canadian Task Force classification II-1). SETTING:
      University-affiliated teaching hospital. Patients. Sixty-six women with
      menorrhagia. INTERVENTION: Eighteen patients were treated with the ThermaChoice
      thermal balloon system for 8 minutes at 80 to 150 mm Hg pressure, 15 were treated
      for 8 minutes at 151 to 180 mm Hg, and 33 were treated for 12 to 16 minutes at
      151 to 180 mm Hg. MEASUREMENTS AND MAIN RESULTS: No intraoperative complications
      occurred and postoperative morbidity was minimal. At 12 to 24 months follow-up,
      persistent menorrhagia was reported in 56% of women treated at 80 to 150 mm Hg
      compared with 20% treated at 151 to 180 mm Hg for 8 minutes (p = 0.01), and in
      24% treated for 12 to 16 minutes at 151 to 180 mm Hg (p = 0.1). CONCLUSION:
      Thermal balloon endometrial ablation is a safe and effective treatment for
      menorrhagia. Balloon pressure greater than 150 mm Hg increased the effectiveness
      of treatment. Success was not affected or influenced by increasing the duration
      of treatment from 8 to 12 minutes or more.

PMID- 10924626
TI  - Model to determine resistance and leakage-dependent flow on flow performance of
      laparoscopic insufflators to predict gas flow rate of cannulas.
AB  - STUDY OBJECTIVE: To characterize insufflator CO2 gas flow performance to predict
      gas flow rate with standard cannulas. DESIGN: Prospective, observational study
      (Canadian Task Force classification II-2). SETTING: Laboratory of university
      clinic. PATIENTS: None. Intervention. Gas flow (L/min) and average pressure (mm
      Hg) inside an abdomen model were measured at 12 mm Hg nominal pressure during
      steady state. MEASUREMENTS AND MAIN RESULTS: An abdomen box model for laboratory
      measurements was designed with different entrance and exit diameters simulated
      with hole disks from 0.5 to 7.6 mm. With a computer-based data-acquisition model,
      five insufflators (Olympus 9L and 16L, Storz 10L and 30L, HiTec 16L) were
      evaluated with 150 disk combinations. Flow performance in three-dimensional
      profiles showed different flow rates for all insufflators depending on resistance
      and leakage combination, maximum flow rate, and insufflation principle. Maximum
      flow was reached without resistance only in the insufflation system at high
      leakage rates. Low-pressure principle is more affected by resistance. Cannula
      flow rates at 12 mm Hg and 15 L/minute leakage ranged from 4.8 (Origin) to 6.0
      L/minute (Storz HiCap) for Olympus 9-L insufflators and from 5.4 (Origin) to
      15.10 L/minute (Storz HiCap) for Storz 30-L Thermoflator. Reusable cannulas have
      more flow efficacy than disposable ones, especially with high-flow insufflators,
      because of larger diameter at insufflation supply. CONCLUSION: Gas flow depends
      not only on maximum flow of insufflators but also on resistance of cannulas and
      leakage rate. With this model it is possible to predict the real, available flow
      of insufflator-cannula combinations for the first time. Improved resistance of
      all components can save insufflation time.

PMID- 10924628
TI  - Emergency endometrial resection in women with acute, severe uterine bleeding.
AB  - STUDY OBJECTIVE: To evaluate the efficacy and safety of endometrial hysteroscopic
      resection in the treatment of severe uterine bleeding. DESIGN: Pilot feasibility
      study (Canadian Task Force classification II-2). SETTING: Department of
      gynecology at a general hospital. PATIENTS: Twenty-six women with severe uterine
      bleeding. INTERVENTION: Hysteroscopic transcervical endometrial resection under
      general anesthesia. MEASUREMENTS AND MAIN RESULTS: Bleeding had a benign organic
      cause in 25 women. One endometrial carcinoma was detected in endometrial chips in
      a postmenopausal woman and was managed with hysterectomy. Fifteen cycling women
      experienced complete remission of uterine bleeding; one underwent hysterectomy
      during follow-up. Atrophic endometrium was present in nine menopausal women
      during follow up. CONCLUSION: Endometrial transcervical resection was effective
      in controlling heavy bleeding, preventing future episodes of severe bleeding, and
      avoiding further medical or surgical treatment during 19 months of follow-up.

PMID- 10924627
TI  - Hysteroscopic endometrial ablation is an effective alternative to hysterectomy in
      women with menorrhagia and large uteri.
AB  - STUDY OBJECTIVES: To examine the feasibility, safety, and outcome of
      hysteroscopic endometrial ablation, and to determine the volume of fluid absorbed
      during resection versus rollerball coagulation in women with menorrhagia and
      large uteri. DESIGN: Retrospective review (Canadian Task Force classification II
      2). SETTING: University-affiliated teaching hospital. PATIENTS: Forty-two
      consecutive patients (mean +/- SD age 45.6 +/- 6 yrs) with uterine size greater
      than 12 weeks (cavity >12 cm). Intervention. Endometrial ablation; 26 (62%) women
      were pretreated to thin the endometrium. MEASUREMENTS AND MAIN RESULTS: Resection
      was performed in 27 patients (65%) and rollerball coagulation in 15 (35%).
      Ablation was successfully performed in all patients in a day surgery setting.
      Multiple regression analysis examined the relationship of uterine size,
      pretreatment, procedure, and duration of surgery to amount of glycine absorbed.
      Glycine absorption was higher with resection than with coagulation (p = 0.04).
      Fluid absorption correlated with type of procedure (r = 0.32, p = 0.04) but not
      with duration of the procedure, uterine size, or pretreatment. One patient with
      uterine fibroids and one with endometrial adenocarcinoma had hysterectomy. With
      follow-up of 39 (95%) of 41 women (excluding the one with adenocarcinoma) for 14
      +/- 2 months, 38 (93%) were very satisfied. Thirty (73%) had amenorrhea, six
      (15%) had hypomenorrhea (<3 pads/day), and three (7%) had eumenorrhea (<10
      pads/day). CONCLUSION: Hysteroscopic endometrial ablation may be a feasible,
      safe, and effective alternative to hysterectomy in women with menorrhagia and
      large uteri.

PMID- 10924629
TI  - Role of endometrial suppression on the frequency of intrauterine adhesions after
      resectoscopic surgery.
AB  - STUDY OBJECTIVES: To evaluate long-term effects of operative hysteroscopy on the
      development of intrauterine adhesions (IUA), and to determine whether
      hypoestrogenism has a modulatory role in preventing IUA. DESIGN: Prospective,
      randomized study (Canadian Task Force classification I). SETTING: Tertiary-care
      teaching hospital. PATIENTS: Ninety-five women requiring resectoscopic surgery.
      Intervention. Hysteroscopic surgery using the resectoscope and 1.5% glycine for
      uterine distention. MEASUREMENTS AND MAIN RESULTS: Indications for hysteroscopy
      were polyps (28 patients), solitary myoma (32), multiple myomata (20), and
      uterine septa (15). Patients in each group were randomized to endometrial
      suppression with danazol or placebo. Second-look office hysteroscopy with CO2 for
      uterine distention was performed after the first menses after surgery to assess
      the frequency, extent, and severity of IUA. The likelihood and severity of IUA
      depended on the pathology treated at initial surgery. Of women treated for polyps
      and uterine septa, in only one with septa (placebo group) developed IUA. Mild IUA
      formation was present in 10 patients (31.3%) with solitary fibroids and 9 (45.5%)
      with multiple myomata. The frequency was similar in placebo- and danazol-treated
      groups with both solitary and multiple myomas (50% and 44.4% vs 50% and 55.6%).
      All IUA were lysed during second-look surgery, except in one woman with multiple
      myomata who required repeat resectoscopy. CONCLUSION: Intrauterine adhesions are
      the major long-term complication of operative hysteroscopy, with frequency
      dependent on the pathology initially treated. Second-look office hysteroscopy is
      a cost-effective method of diagnosing and lysing IUA after resectoscopy.

PMID- 10924630
TI  - Laparoscopic treatment of hydrosalpinx: factors affecting pregnancy rate.
AB  - STUDY OBJECTIVE: To evaluate the efficacy of laparoscopic surgery in a series of
      women with hydrosalpinx. DESIGN: Prospective, observational study (Canadian Task
      Force classification II-2). Setting. University-affiliated hospital. PATIENTS:
      Sixty-one women undergoing bilateral neosalpingostomy and restoration of tubal
      ovarian anatomy laparoscopically, and followed for 24 months. INTERVENTION: Video
      controlled operative laparoscopy using standard four-puncture technique.
      MEASUREMENTS AND MAIN RESULTS: During 24-month follow-up, cumulative intrauterine
      pregnancy rates at 6-month intervals were 6.8%, 13.6%, 20.5%, and 20.5% for
      patients with only distal tubal obstruction and 12%, 23%, 29%, and 29% for those
      with mild degree of tubal disease and periadnexal adhesions. Miscarriage rate for
      intrauterine pregnancies was zero in both groups. CONCLUSION: Operative
      laparoscopy seems to be an effective treatment for hydrosalpinx in terms of
      pregnancy outcome.

PMID- 10924631
TI  - Stress responses during laparoscopy with CO2 insufflation and with mechanical
      elevation of the abdominal wall.
AB  - STUDY OBJECTIVE: To compare the intensity of stress responses caused by
      laparoscopy combined with CO2 insufflation (CI) with those caused by mechanical
      elevation of the abdominal wall (MEA). DESIGN: Prospective study (Canadian Task
      Force classification I). SETTING: Tertiary care university hospital. PATIENTS:
      Thirty-one women. Intervention. Laparoscopy, 16 with CI and 15 with MEA.
      MEASUREMENTS AND MAIN RESULTS: Circulating levels of norepinephrine, epinephrine,
      cortisol, and interleukin (IL)-6 were compared in the two groups. Arterial
      partial pressure of CO2 (PaCO2) did not increase during laparoscopy by either
      method. Plasma norepinephrine and epinephrine levels increased after extubation
      in the MEA group but not in the CI group. Circulating cortisol levels in both
      groups increased during laparoscopy; mean intraoperative levels were higher in
      the CI group. Serum IL-6 levels increased after extubation in the MEA but not the
      CI group. Mean heart rate increased during laparoscopy in both groups, whereas
      blood pressure increased only in the CI group. More patients in the MEA group
      required postoperative analgesia. CONCLUSION: Laparoscopy with MEA caused more
      pronounced adrenosympathetic and cytokine responses than that with CI when PaCO2
      was maintained within the range of normocapnia.

PMID- 10924632
TI  - Laparoscopic surgery for complex ovarian masses.
AB  - STUDY OBJECTIVE: To assess the value of laparoscopy in managing complex ovarian
      masses. DESIGN: Retrospective, observational analysis (Canadian Task Force
      classification II-2). SETTING: University-based, tertiary level center for
      endoscopic surgery. PATIENTS: Two hundred eleven consecutive women.
      INTERVENTIONS: Laparoscopic surgery including ovary-preserving surgery, salpingo
      oophorectomy, adhesiolysis, and pelvic lymphadenectomy. MEASUREMENTS AND MAIN
      RESULTS: Patients were selected on the basis of preoperative ultrasound findings.
      Intraoperative appearance of the tumors as well as results from frozen section
      examinations were compared with histologic results. Two hundred sixteen pelvic
      masses were benign. In 10 patients, early ovarian cancer, borderline tumors,
      tubal cancer, or secondary ovarian, nongynecologic pathology was managed
      primarily by laparoscopy and confirmed histologically. Three of these 10 women
      underwent standard radical open surgery within 1 week. The true nature of masses
      was not recognized at the time of laparoscopy in three patients with malignant
      findings. Patients with malignant tumors were followed for 5 years. CONCLUSION:
      Although most complex ovarian masses can be managed by laparoscopy, the
      possibility of overlooking malignancy remains, even with frozen section
      examination. Whether or not laparoscopy compromises clinical outcome compared
      with laparotomy is not fully understood. Prospective studies to address this
      important clinical question are urgently needed.

PMID- 10924633
TI  - The role of outpatient diagnostic hysteroscopy in identifying anatomic pathology
      and histopathology in the endometrial cavity.
AB  - STUDY OBJECTIVE: To evaluate the role of outpatient diagnostic hysteroscopy.
      DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING:
      University teaching hospital-based outpatient clinic. PATIENTS: One thousand six
      hundred women, 67.3% premenopausal and 32.7% postmenopausal. INTERVENTION:
      Diagnostic hysteroscopy without premedication or anesthesia; endometrial sampling
      or hysteroscopy-guided biopsy was performed when appropriate. MEASUREMENTS AND
      MAIN RESULTS: Outpatient hysteroscopy was successfully performed in 1468 women
      (91.8%). Eleven women (0. 7%) developed vasovagal response during the procedure,
      18 required hospital admission because of pain or hemorrhage, and 2 were
      suspected of having uterine perforation. All recovered spontaneously without
      intervention. Intrauterine anatomic pathology was diagnosed in 17.0%; the overall
      frequency of myomas and endometrial polyps was 12.3% and 7.1%, respectively. The
      sensitivity and positive predictive value of hysteroscopy without biopsy in
      diagnosing endometrial carcinoma were only 58.8% and 20.8%, respectively. Of 1112
      women with hysteroscopic impression of normal or atrophic endometrium, 10 (0.9%)
      had endometrial hyperplasia on biopsy. CONCLUSION: Hysteroscopy without biopsy
      carries low sensitivity and positive predictive value in the diagnosis of
      endometrial carcinoma and hyperplasia. In our opinion the predictive value of a
      negative hysteroscopy is inadequate, and endometrial biopsy should be performed
      during hysteroscopy for accurate diagnosis of endometrial histopathology.

PMID- 10924634
TI  - Surgical management of interstitial pregnancy.
AB  - Interstitial pregnancy is a rare and potentially dangerous event. Standard
      treatment involves laparotomy with cornual resection or hysterectomy, with few
      reported cases of laparoscopic management. A 14-week, 6-cm interstitial pregnancy
      was treated laparoscopically, without cornual resection or hysterectomy.
      Gestational products were removed from the fetal side of the implantation site
      through a salpingotomy incision through myometrium. In selected patients, this
      procedure can be accomplished safely and efficaciously while preserving
      reproductive function and avoiding laparotomy.

PMID- 10924635
TI  - Successful intrauterine pregnancy after endometrial ablation.
AB  - The frequency of pregnancy after endometrial ablation is reported in the
      literature to be 0.7%, with a variety of complications and adverse outcomes for
      the fetus. A 30-year-old woman underwent rollerball endometrial ablation for
      menometrorrhagia. Her menses returned to normal and she conceived 16 months
      later. The pregnancy was uncomplicated apart from diet-controlled gestational
      diabetes and cesarean delivery for a transverse lie. To our knowledge, this is
      the first literature report of a viable pregnancy after rollerball ablation.

PMID- 10924637
TI  - Laparoscopic management of neonatal ovarian cysts.
AB  - A laparoscopic approach was used in four infants with antenatally diagnosed
      ovarian cysts requiring surgical intervention. Operating time ranged from 60 to
      90 minutes, there were no intraoperative or postoperative complications, and all
      infants were discharged within 23 hours after surgery. If performed by
      experienced practitioners, microendoscopy is an alternative to laparotomy in
      neonates requiring surgical intervention for ovarian cysts.

PMID- 10924636
TI  - Ovarian failure after uterine artery embolization for treatment of myomas.
AB  - Uterine artery embolization (UAE) is an effective, safe, nonsurgical treatment
      for uterine myomas. Although menstrual irregularities and transient amenorrhea
      have occurred after UAE, these reports did not provide proper hormonal
      documentation of ovarian failure. Our patient experienced elevated follicle
      stimulating hormone (FSH) levels and vasomotor symptoms (hot flushes) within 4
      weeks after the procedure. To our knowledge, this is the first report in the
      literature of ovarian failure after UAE confirmed by comparing preprocedure FSH
      levels with postprocedure levels over 12 months.

PMID- 10924638
TI  - Laparoscopic management of intestinal endometriosis.
AB  - Intestinal involvement by endometriosis traditionally required open laparotomy
      for bowel resection and anastomosis. Operative laparoscopy may offer the most
      effective form of treatment for these women. Two women with endometriosis of the
      rectum and right hemicolon, respectively, underwent transvaginal resection of the
      rectum and laparotomy for hemicolectomy, assisted by laparoscopy. The only
      morbidity was postoperative ileus in the former patient. Both women were
      asymptomatic at the 6-week postoperative visit.

PMID- 10924639
TI  - Laparoscopic myomectomy in a patient with Mayer-Rokitansky-Kuster-Hauser
      syndrome.
AB  - A 36-year-old woman had primary amenorrhea, pelvic pain, Mayer-Rokitansky-Kuster
      Hauser syndrome, and an 8.5-cm, solid pelvic mass. The leiomyoma uteri was
      removed laparoscopically from the vestigial mullerian duct with secondary
      vaginopoiesis. The patient had a satisfactory clinical outcome. Finding of a
      leiomyoma in a patient with Rokitansky syndrome is rare. To our knowledge this is
      the first such case in which the myoma was removed by laparoscopy.

PMID- 10924640
TI  - Laparoscopic repair of ureteral transection.
AB  - Injury to the ureter is a possible complication of laparoscopic surgery.
      Traditionally, it is repaired by laparotomy. During laparoscopic surgery for
      bilateral ovarian remnants in a 29-year-old woman, the left ureter was
      transected. The ureter was repaired by primary end-to-end anastomosis by
      laparoscopy. The patient recovered uneventfully, and postoperative intravenous
      puelogram confirmed the repair to be intact.

PMID- 10924641
TI  - Unrecognized bladder perforation during operative laparoscopy.
AB  - During operative laparoscopy in a 42-year-old woman, 12-mm trocar lacerations
      occurred through anterior and posterior walls of the bladder but were not
      recognized. This case demonstrates important issues related to predicting,
      avoiding, detecting, and treating bladder trauma associated with laparoscopic
      surgery. It also indicates that some classic warning signs of accidental
      cystotomy may be absent or delayed in appearance.

PMID- 10924642
TI  - Torsion of single normal adnexa in a premenarchal girl.
AB  - A 9-year-old girl had torsion of a normal adnexa. She also had absence of the
      contralateral adnexa, most probably due to undiagnosed ovarian torsion.

PMID- 10924643
TI  - Isolated tubal torsion managed laparoscopically.
AB  - Adnexal cystic lesions in women of reproductive age are common. Most are
      functional ovarian cysts, followed by paraovarian cysts, hydrosalpinx, and
      adnexal torsion. A 34-year-old woman experienced mild abdominal pain, nausea, and
      low-grade fever. She received empiric antibiotics in an outpatient clinic after a
      diagnosis of tubo-ovarian abscess. After 3 days she was referred to our hospital
      with no improvement in symptoms or signs. Isolated fallopian tube torsion was
      diagnosed and successfully treated by laparoscopy. Laparoscopy played an
      important role in making an accurate diagnosis and avoiding unnecessary delays in
      treatment.

PMID- 10924644
TI  - Laparoscopic excision of a mesenteric cyst diagnosed preoperatively as an ovarian
      cyst.
AB  - Mesenteric cysts are uncommon benign, abdominal tumors usually managed by general
      surgeons. We encountered an unusual mesenteric cyst that was diagnosed
      preoperatively as an ovarian cyst. It was located in the pelvic cavity inside the
      mesoappendix. We excised the cyst and adjacent vermiform appendix by laparoscopy.
      Histopathologic examination revealed mucinous cystadenoma. To the best of our
      knowledge, this is the first reported case of a mesenteric cyst removed by a
      gynecologic laparoscopist.

PMID- 10924645
TI  - Is there a Persian Gulf War syndrome? Evidence from a large population-based
      survey of veterans and nondeployed controls.
AB  - PURPOSE: Concerns have been raised about whether veterans of the Gulf War have a
      medical illness of uncertain etiology. We surveyed veterans to look for evidence
      of an illness that was unique to those deployed to the Persian Gulf and was not
      seen in comparable military controls. SUBJECTS AND METHODS: A population-based
      sample of veterans (n = 1,896 from 889 units) deployed to the Persian Gulf and
      other Gulf War-era controls (n = 1799 from 893 units) who did not serve in the
      Gulf were surveyed in 1995-1996. Seventy-six percent of eligible subjects,
      including 91% of located subjects, answered questions about commonly reported and
      potentially important symptoms. We used factor analysis, a statistical technique
      that can identify patterns of related responses, on a random subset of the
      deployed veterans to identify latent patterns of symptoms. The results from this
      derivation sample were compared with those obtained from a separate validation
      sample of deployed veterans, as well as the nondeployed controls, to determine
      whether the results were replicable and unique. RESULTS: One half (50%) of the
      deployed veterans and 14% of the nondeployed controls reported health problems
      that they attributed to military service during 1990-1991. Compared with the
      nondeployed controls, the deployed veterans had significantly greater prevalences
      of 123 of 137 (90%) symptoms; none was significantly lower. Factor analysis
      identified three replicable symptom factors (or patterns) in the deployed
      veterans (convergent correlations > or =0.85). However, these patterns were also
      highly replicable in the nondeployed controls (convergent correlations of 0.95 to
      0.98). The three factors also accounted for similar proportions of the common
      variance among the deployed veterans (35%) and nondeployed controls (30%).
      CONCLUSIONS: The increased prevalence of nearly every symptom assessed from all
      bodily organ systems among the Gulf War veterans is difficult to explain
      pathophysiologically as a single condition. Identification of the same patterns
      of symptoms among the deployed veterans and nondeployed controls suggests that
      the health complaints of Gulf War veterans are similar to those of the general
      military population and are not consistent with the existence of a unique Gulf
      War syndrome.

PMID- 10924646
TI  - The health of mothers of children with cutaneous neonatal lupus erythematosus
      differs from that of mothers of children with congenital heart block.
AB  - PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of
      maternal autoantibodies. The aim of this study was to determine the risk of
      connective tissue disorders in mothers of children with cutaneous neonatal lupus
      erythematosus, as compared with the risk in mothers of children with congenital
      heart block, which is also often caused by maternal autoantibodies. SUBJECTS AND
      METHODS: We prospectively studied all mothers of children with cutaneous neonatal
      lupus erythematosus during a 14-year period at the Hospital for Sick Children,
      Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for
      study. The health and antibody status of the mothers were determined at the birth
      of the child and at followup. RESULTS: All mothers had anti-Ro antibodies at the
      time of birth. Initially 10 mothers were healthy and 14 mothers had either a
      defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean
      follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue
      disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained
      asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital
      heart block were asymptomatic at follow-up (P <0.005). CONCLUSIONS: The majority
      of mothers of children with cutaneous neonatal lupus erythematosus had a defined
      or undifferentiated autoimmune disorder at the time of the child's birth, and
      others developed these conditions during follow-up. The health of these mothers
      appears to differ from that of mothers of children with congenital heart block.

PMID- 10924647
TI  - Outcomes of coronary angioplasty procedures performed in rural hospitals.
AB  - PURPOSE: To determine how many rural hospitals in the United States performed
      coronary angioplasty; to compare patient outcomes in rural and urban hospitals;
      and to assess whether outcomes were better in rural hospitals in which more
      procedures were performed. SUBJECTS AND METHODS: In 1996, among patients 65 years
      of age and older, 201,869 coronary angioplasties were performed in 996 hospitals
      that were included in the Medicare Provider Analysis and Review files. Geographic
      location was defined as rural or urban, according to U.S. Census Bureau criteria.
      Outcome variables were in-hospital death and coronary artery bypass surgery
      performed during the same admission. Hospital volumes were categorized as low (<
      or = 100 cases or fewer per year), medium (101 to 200 cases per year), or high (>
      200 cases per year). RESULTS: Fifty-one rural hospitals accounted for 4% of all
      angioplasties performed. After angioplasty, in-hospital mortality was greater in
      rural hospitals (8.1% versus 6.4%, P = 0.001) among patients with acute
      myocardial infarction, but was not different for patients without infarction
      (1.4% versus 1.3%, P = 0.41). Coronary artery bypass surgery rates during the
      same admission were similar in rural and urban hospitals. In general, in-hospital
      mortality and same-admission surgery rates were lower in high-volume centers in
      both rural and urban areas. CONCLUSION: Although in-hospital mortality after
      angioplasty for acute myocardial infarction was worse in low- and medium-volume
      rural centers, overall outcomes in rural and urban hospitals were similar.

PMID- 10924648
TI  - Health-related quality of life in patients with human immunodeficiency virus
      infection in the United States: results from the HIV Cost and Services
      Utilization Study.
AB  - PURPOSE: To measure health-related quality of life among adult patients with
      human immunodeficiency virus (HIV) disease; to compare the health-related quality
      of life of adults with HIV with that of the general population and with patients
      with other chronic conditions; and to determine the associations of demographic
      variables and disease severity with health-related quality of life. SUBJECTS AND
      METHODS: We studied 2,864 HIV-infected adults participating in the HIV Cost and
      Services Utilization Study, a probability sample of adults with HIV receiving
      health care in the contiguous United States (excluding military hospitals,
      prisons, or emergency rooms). A battery of 28 items covering eight domains of
      health (physical functioning, emotional well-being, role functioning, pain,
      general health perceptions, social functioning, energy, disability days) was
      administered. The eight domains were combined into physical and mental health
      summary scores. SF-36 physical functioning and emotional well-being scales were
      compared with the US general population and patients with other chronic diseases
      on a 0 to 100 scale. RESULTS: Physical functioning was about the same for adults
      with asymptomatic HIV disease as for the US population [mean (+/- SD) of 92+/-16
      versus 90+/-17) but was much worse for those with symptomatic HIV disease (76+/
      28) or who met criteria for the acquired immunodeficiency syndrome (AIDS; 58+/
      31). Patients with AIDS had worse physical functioning than those with other
      chronic diseases (epilepsy, gastroesophageal reflux disease, clinically localized
      prostate cancer, clinical depression, diabetes) for which comparable data were
      available. Emotional well-being was comparable among patients with various stages
      of HIV disease (asymptomatic, 62+/-9; symptomatic, 59+/-11; AIDS, 59+/-11), but
      was significantly worse than the general population and patients with other
      chronic diseases except depression. In multivariate analyses, HIV-related
      symptoms were strongly associated with physical and mental health, whereas race,
      sex, health insurance status, disease stage, and CD4 count were at most weakly
      associated with physical and mental health. CONCLUSIONS: There is substantial
      morbidity associated with HIV disease in adults. The variability in health
      related quality of life according to disease progression is relevant for health
      policy and allocation of resources, and merits the attention of clinicians who
      treat patients with HIV disease.

PMID- 10924649
TI  - Cost effectiveness of vaccination strategies in adults without a history of
      chickenpox.
AB  - PURPOSE: Some authorities recommend varicella antibody testing or vaccination for
      adults without a history of chickenpox, but the cost effectiveness of these
      interventions is uncertain. SUBJECTS AND METHODS: Using a Markov decision model,
      we estimated the cost effectiveness of three strategies for adults with no
      history of chickenpox: no vaccination, varicella antibody testing followed by
      vaccination for those without antibody, and vaccinating all. Societal and third
      party payer perspectives were taken, with costs and benefits discounted at 3% per
      year. Assumptions for the baseline analysis were chosen to bias against no
      vaccination. RESULTS: In the baseline analysis for 20- to 29-year-old patients,
      testing followed by vaccination compared with no vaccination is cost saving from
      a societal perspective and costs $6,670 per quality-adjusted life-year (QALY)
      gained from a third-party payer perspective. When less favorable assumptions are
      used, results are sensitive to the rates of compliance with vaccination follow
      up; testing followed by vaccination costs more than $50,000 per QALY if <75%
      comply. For patients 30 years of age and older, the incremental cost of testing
      followed by vaccination is at least $97,100 per QALY compared with no
      vaccination, with costs greater than $50,000 per QALY unless testing costs less
      than $7.73, the chickenpox case-fatality rate is >0.067% (baseline 0.025%), or
      immunity with no chickenpox history is <25% (baseline 71%). In either age group,
      vaccinating all has an incremental cost of $2 to $16 million per QALY gained
      compared with testing followed by vaccination. CONCLUSION: Testing followed by
      vaccination for varicella in US adults aged 20 to 29 years may be cost effective
      by conventional criteria but is sensitive to rates of compliance with vaccination
      protocols. Testing or vaccination of older adults is expensive but may be cost
      effective in patients with lower probabilities of immunity or in those who have a
      greater risk of complications from chickenpox.

PMID- 10924650
TI  - Low-dose methotrexate for the treatment of patients with large granular
      lymphocyte leukemia associated with rheumatoid arthritis.

PMID- 10924651
TI  - Preoperative localization of parathyroid adenomas using 99mTc-MIBI scintigraphy.

PMID- 10924652
TI  - Enhanced sensitivity of the peripheral cholinergic vascular response in patients
      with chronic fatigue syndrome.

PMID- 10924653
TI  - Diagnostic dilemma. Systemic sarcoidosis.

PMID- 10924654
TI  - The heart and skin of neonatal lupus: does maternal health matter?

PMID- 10924655
TI  - Leukemia of large granular lymphocytes and rheumatoid arthritis.

PMID- 10924656
TI  - Varicella vaccination: to test or not to test.

PMID- 10924657
TI  - Coronary interventions: keeping score.

PMID- 10924659
TI  - Answer to diagnostic dilemma.

PMID- 10924658
TI  - Does tenure still fit the needs of medical school faculty?

PMID- 10924660
TI  - Meeting report; "Molecular neurobiological mechanisms in schizophrenia: seeking a
      synthesis," April 11-14, 1999.
AB  - A meeting on the molecular and neurobiological basis of schizophrenia was held
      April 11-14, 1999 at the Banbury Center of The Cold Spring Harbor Laboratory,
      Cold Spring Harbor, New York. This report is a summary of the predominant views
      of the participants, as perceived by the organizers. The purpose of this meeting
      was integrative-to bring together in a relaxed environment three dozen
      outstanding scientists in disparate underlying disciplines: psychiatry,
      psychology, genetics, neurobiology, biochemistry, molecular biology, and
      pharmacology. Brief talks emphasized concepts and questions rather than
      presentation of data. Exchanges of information and concepts provided an emerging
      synthesis of current and novel, even highly speculative, ideas. The reader is
      cautioned that the ideas, data supporting them, and data interpretations are not
      critiqued in this report. Nor is there much distinction made between speculations
      and findings that have more experimental support. The main questions and
      conclusions that emerged are presented in this report, which covers the
      following: 1) macrobiology (what schizophrenia is in terms of definition and
      improved diagnostics, genetics and environment, brain structure, development, and
      mind), 2) cell and molecular biology (defects of the expressed disease at both
      the membrane and nuclear levels, molecular defects of development, neuroreceptor
      genes and transcriptional control, and ligands), 3) therapies (current
      approaches, possible targets, and animal models), and 4) newer approaches (gene
      expression, early treatment and prevention strategies, and other problems). Two
      references per participant and abstracts (available from the organizers) served
      as a common basis.

PMID- 10924661
TI  - Levels of mRNAs encoding synaptic vesicle and synaptic plasma membrane proteins
      in the temporal cortex of elderly schizophrenic patients.
AB  - BACKGROUND: Electron microscopy and biochemical studies indicate that
      developmental abnormalities in synaptic organization may be present in brains of
      schizophrenic patients. This study determined whether these synaptic
      abnormalities are reflected in differential or uniform alterations in the
      expression of various synaptic protein genes in the left superior temporal gyrus
      of schizophrenic patients. METHODS: Levels of mRNAs encoding four synaptic
      vesicle proteins (synaptotagmin I [p65], rab3a, synaptobrevin 1, and
      synaptobrevin 2) and two synaptic plasma membrane proteins (syntaxin 1A and SNAP
      25) were measured postmortem in the left superior temporal gyrus from elderly (58
      95 years) schizophrenic patients (n = 14) and age-matched control subjects (n =
      9). RESULTS: There were significant negative correlations between age and levels
      of synaptotagmin I (p65), rab3a, synaptobrevin 1, SNAP-25, and syntaxin 1A mRNAs
      in schizophrenic patients (-.692 < r < -.517,.003 < p <.030) but not in control
      subjects. Levels of all six synaptic mRNAs studied were increased in the younger
      (58-79 years) subgroup of schizophrenic patients compared to control subjects and
      older (80-95 years) subgroup of schizophrenic patients. CONCLUSIONS: That similar
      abnormalities were found for mRNAs encoding different synaptic vesicle and
      synaptic plasma membrane proteins suggests that they reflect overall
      neurodevelopmental abnormalities in synaptic connectivity in the temporal cortex
      of schizophrenic patients rather than changes in the number of synaptic vesicles
      per synapse or abnormalities in a specific synaptic function.

PMID- 10924662
TI  - Smooth pursuit eye movements in schizophrenia and attentional dysfunction: adults
      with schizophrenia, ADHD, and a normal comparison group.
AB  - BACKGROUND: Smooth pursuit eye movement (SPEM) abnormalities are found in
      schizophrenia. These deficits often are explained in the context of the
      attentional and inhibitory deficits central to schizophrenia psychopathology. It
      remains unclear, however, whether these attention-associated eye movement
      abnormalities are specific to schizophrenia or are a nonspecific expression of
      attentional deficits found in many psychiatric disorders. Adult attention
      deficit/hyperactivity disorder (ADHD) is an alternative disorder with chronic
      attentional and inhibitory dysfunction. Thus, a comparison of SPEM in adult
      schizophrenia and adult ADHD will help assess the specificity question. METHODS:
      SPEM is recorded during a 16.7 degrees per second constant velocity task in 17
      adults with ADHD, 49 adults with schizophrenia, and 37 normal adults; all groups
      included individuals between ages 25-50 years. RESULTS: Smooth pursuit gain and
      the frequency of anticipatory and leading saccades are worse in schizophrenic
      subjects, with normal and ADHD subjects showing no differences on these
      variables. CONCLUSIONS: Many attention-associated SPEM abnormalities are not
      present in most subjects with ADHD, supporting the specificity of these findings
      to the attentional deficits seen in schizophrenia.

PMID- 10924663
TI  - Cerebellar functional abnormalities in schizophrenia are suggested by classical
      eyeblink conditioning.
AB  - BACKGROUND: Previous research suggests that schizophrenia may result from
      disruptions in a cortico-cerebellar-thalamic-cortical circuit (CCTCC) producing a
      mental incoordination or "cognitive dysmetria." To further evaluate the
      cerebellar contribution to this disrupted circuitry, medication-free patients
      with schizophrenia completed classical eyeblink conditioning, a cerebellar
      mediated learning task. METHODS: For classical eyeblink conditioning, 70 trials
      with a tone conditioned stimulus (CS) and air puff unconditioned stimulus (US)
      were presented to 15 patients with schizophrenia and 15 healthy control subjects.
      Acquisition rate for the conditioned response (CR) and response timing were
      compared between the two groups. RESULTS: Patients with schizophrenia displayed
      facilitated conditioning compared to control subjects based on a greater number
      of CRs during the session and a faster acquisition of the learned response.
      CONCLUSIONS: Facilitated conditioning suggests that an enhanced excitability in
      the cerebellum occurs as part of a disrupted CCTCC in schizophrenia. The enhanced
      cerebellar-mediated associative learning may be maladaptive in the context of
      normal cerebro-cerebellar interactions, leading to the characteristic motor and
      mental incoordination of the disorder. Classical eyeblink conditioning may
      provide a useful model system for studying cerebellar involvement in the
      pathogenesis and treatment of schizophrenia.

PMID- 10924664
TI  - An event-related potential investigation of response inhibition in schizophrenia
      and psychopathy.
AB  - BACKGROUND: Schizophrenia and psychopathy are both characterized by impulsive,
      poorly planned behavior. This behavior may originate from a weak or poorly
      coordinated response inhibition system. We tested the hypothesis that
      schizophrenia and psychopathy are associated with abnormal neural processing
      during the suppression of inappropriate responses. METHODS: The participants were
      schizophrenic patients, nonpsychotic psychopaths, and nonpsychotic,
      nonpsychopathic control subjects (defined by the Hare Psychopathy Checklist
      Revised), all incarcerated in a maximum security psychiatric facility. We
      recorded behavioral responses and event-related potentials (ERPs) during a Go/No
      Go task. RESULTS: Schizophrenic patients made more errors of commission than did
      the nonpsychopathic offenders. As expected, the nonpsychopathic nonpsychotic
      participants showed greater frontal ERP negativity (N275) to the No Go stimuli
      than to the Go stimuli. This effect was small in the schizophrenic patients and
      absent in the psychopaths. For the nonpsychopaths, the P375 ERP component was
      larger on Go than on No Go trials, a difference that was absent in schizophrenic
      patients and in the opposite direction in psychopaths. CONCLUSIONS: These
      findings support the hypothesis that the neural processes involved in response
      inhibition are abnormal in both schizophrenia and psychopathy; however, the
      nature of these processes appears to be different in the two disorders.

PMID- 10924665
TI  - Effects of stimulus intensity on the efficacy of bilateral ECT in schizophrenia:
      a preliminary study.
AB  - BACKGROUND: This preliminary study examined the effects of electrical stimulus
      intensity on the speed of response and efficacy of bilateral electroconvulsive
      therapy (ECT) in the treatment of schizophrenia. METHODS: Sixty-two patients with
      schizophrenia received combination treatment with bilateral ECT and flupenthixol.
      Using a randomized, double-blind design, the effects of three dosages of the ECT
      electrical stimulus were examined. Patients were treated with a stimulus
      intensity that was just above seizure threshold, two-times threshold, or four
      times threshold. Assessments of outcome used the Brief Psychiatric Rating Scale,
      Global Assessment of Functioning, and the Mini-Mental State Exam. RESULTS: Thirty
      three of sixty-two patients met remitter criteria, including maintaining
      improvement over a 3-week stabilization period. The dosage groups were equivalent
      in the number of patients who met remitter criteria. The low-dose remitter group
      (n = 11) received more ECT treatments and required more days to meet remitter
      status than both the twofold (n = 11) and fourfold remitter groups (n = 11).
      There was no difference among the groups in change in global cognitive status as
      assessed by the Mini-Mental State Exam. CONCLUSIONS: This preliminary study
      indicates that treatment with high-dosage bilateral ECT speeds clinical response
      in patients with schizophrenia. There may be a therapeutic window of stimulus
      intensity in impacting on the efficacy of bilateral ECT, which needs further
      study. A more sensitive battery of cognitive tests should be used in future
      research.

PMID- 10924667
TI  - Inhibitory control in children with attention-deficit/hyperactivity disorder:
      event-related potentials identify the processing component and timing of an
      impaired right-frontal response-inhibition mechanism.
AB  - BACKGROUND: A core deficit in inhibitory control may account for a wide range of
      dysfunctional behaviors in attention-deficit/hyperactivity disorder (ADHD).
      METHODS: Event-related potentials were measured in 10 children with ADHD and 10
      healthy children during a task specifically involving response inhibition (Stop
      signal task). RESULTS: In response to all Stop signals, control participants
      produced a large negative wave at 200 msec (N200) over right inferior frontal
      cortex, which was markedly reduced in ADHD children. The N200 amplitude was
      significantly correlated across subjects with response-inhibition performance. In
      response to the Go stimuli, ADHD children showed a reduced slow positive wave
      (250-500 msec) in anticipation of failed inhibitions over right frontal scalp
      regions. CONCLUSIONS: ADHD children appear to have an abnormality in an early
      latency, right inferior frontal processing component critical to the initiation
      of normal response-inhibition operations. They also appear to have a right
      frontal abnormality associated to the covert processing of Go stimuli preceding
      failed inhibitions. By providing timing and processing component specificity,
      these results extend the findings of recent functional MRI studies of inhibitory
      control reporting right frontal abnormalities in ADHD.

PMID- 10924666
TI  - 5-HT(1A) receptor activation contributes to ziprasidone-induced dopamine release
      in the rat prefrontal cortex.
AB  - BACKGROUND: Ziprasidone (Zeldox) is a novel antipsychotic with a unique
      combination of antagonist activities at monoaminergic receptors and transporters
      and potent agonist activity at serotonin 5-HT(1A) receptors. 5-HT(1A) receptor
      agonism may be an important feature in ziprasidone's clinical actions because 5
      HT(1A) agonists increase cortical dopamine release, which may underlie efficacy
      against negative symptoms and reduce dopamine D(2) antagonist-induced
      extrapyramidal side effects. This study investigated the in vivo 5-HT(1A) agonist
      activity of ziprasidone by measuring the contribution of 5-HT(1A) receptor
      activation to the ziprasidone-induced cortical dopamine release in rats. METHODS:
      Effects on dopamine release were measured by microdialysis in prefrontal cortex
      and striatum. The role of 5-HT(1A) receptor activation was estimated by assessing
      the sensitivity of the response to pretreatment with the 5-HT(1A) antagonist, WAY
      100635. For comparison, the D(2)/5-HT(2A) antagonists clozapine and olanzapine,
      the D(2) antagonist haloperidol, the 5-HT(2A) antagonist MDL 100,907 and the 5
      HT(1A) agonist 8-OHDPAT were included. RESULTS: Low doses (<3.2 mg/kg) of
      ziprasidone, clozapine, and olanzapine increased dopamine release to
      approximately the same extent in prefrontal cortex as in striatum, but higher
      doses (> or =3.2 mg/kg) resulted in an increasingly preferential effect on
      cortical dopamine release. The 5-HT(1A) agonist 8-OHDPAT produced a robust
      increase in cortical dopamine (DA) release without affecting striatal DA release.
      In contrast, the D(2) antagonist haloperidol selectively increased striatal DA
      release, whereas the 5-HT(2A) antagonist MDL 100,907 had no effect on cortical or
      striatal DA release. Prior administration of WAY-100635 completely blocked the
      cortical DA increase produced by 8-OHDPAT and significantly attenuated the
      ziprasidone- and clozapine-induced cortical DA increase. WAY-100635 pretreatment
      had no effect on the olanzapine-induced DA increase. CONCLUSIONS: The
      preferential increase in DA release in rat prefrontal cortex produced by
      ziprasidone is mediated by 5-HT(1A) receptor activation. This result extends and
      confirms other in vitro and in vivo data suggesting that ziprasidone, like
      clozapine, acts as a 5-HT(1A) receptor agonist in vivo, which may contribute to
      its activity as an antipsychotic with efficacy against negative symptoms and a
      low extrapyramidal side effect liability.

PMID- 10924668
TI  - Hypothalamic pituitary adrenocortical and sympathetic nervous system responses to
      the cold pressor test in Alzheimer's disease.
AB  - BACKGROUND: Increased basal activity of the hypothalamic-pituitary-adrenocortical
      (HPA) axis has been repeatedly demonstrated in Alzheimer's disease (AD), and some
      studies suggest increased basal activity of the sympathetic nervous system (SNS)
      in this disorder; however, the effects of AD on HPA axis or SNS responses to a
      standardized aversive stressor have not been examined. The neuroendocrine
      response to aversive stress may be relevant to the pathophysiology of AD.
      METHODS: Plasma adrenocorticotropic hormone (ACTH), cortisol, norepinephrine
      (NE), and epinephrine responses to a 1-min cold pressor test (CPT) were measured
      in nine medically healthy AD outpatients (age 76 +/- 2 years) and nine age- and
      gender-matched medically healthy cognitively normal older subjects (age 76 +/- 1
      year). RESULTS: The cortisol response to CPT was increased in the AD group but
      the ACTH response did not differ between groups. Basal NE concentrations were
      higher in the AD group. Although NE responses to CPT did not differ between
      groups, the blood pressure response to CPT was higher in the AD subjects.
      CONCLUSIONS: These results suggest increased HPA axis responsiveness to CPT at
      the level of the adrenal cortex in AD. The results also suggest increased basal
      sympathoneural activity and increased cardiovascular responsiveness to
      sympathoneural stimulation in AD under the conditions of this experimental
      protocol. Increased SNS stimulatory modulation of the adrenal cortex is a
      possible mechanism contributing to the observed enhanced cortisol response to CPT
      in these AD subjects.

PMID- 10924669
TI  - Differential expression of a(2a), A(1)-adenosine and D(2)-dopamine receptor genes
      in rat peripheral arterial chemoreceptors during postnatal development.
AB  - The sensitivity of peripheral arterial chemoreceptors in the carotid body to
      hypoxia increases with postnatal maturation. Carotid sinus nerve activity is
      augmented by adenosine binding to A(2a)-adenosine receptors and attenuated by
      dopamine binding to D(2)-dopamine receptors. In this study, we used in situ
      hybridization histochemistry to determine the change in the levels of mRNA
      expression for A(2a) and A(1)-adenosine receptors and D(2)-dopamine receptors in
      the rat carotid body. We also investigated the cellular distribution and possible
      colocalization of these receptor mRNAs and tyrosine hydroxylase (TH) mRNAs during
      the first 2 weeks of postnatal development. By using immunohistocytochemistry, we
      detected A(2a)-adenosine receptor protein in the carotid body and petrosal
      ganglion. We found that A(2a)-adenosine receptor mRNA and protein are expressed
      in the carotid body in animals at 0, 3, 6 and 14 postnatal days. The level of
      A(2a)-adenosine receptor mRNA expression significantly decreased by 14 postnatal
      days (P<0.02 vs. day 0) while D(2)-dopamine receptor mRNA levels significantly
      increased by day 3 and remained greater than D(2)-dopamine receptor mRNA levels
      at day 0 (P<0.001 all ages vs. day 0). TH mRNA was colocalized in cells in the
      carotid body with A(2a) adenosine receptor and D(2)-dopamine receptor mRNAs. A(1)
      adenosine receptor mRNA was not expressed in the carotid body at any of the ages
      examined. In the petrosal ganglion, A(1)-adenosine receptor mRNA was abundantly
      expressed in numerous cells, A(2a)-adenosine receptor mRNA was expressed in a
      moderate number of cells while D(2)-dopamine receptor mRNA was seen in a few
      cells in the rostral petrosal ganglion. In conclusion, using in situ
      hybridization histochemistry, we have shown that mRNA for both the excitatory,
      A(2a)-adenosine receptor, and the inhibitory, D(2)-dopamine receptor, is
      developmentally regulated in presumably type I cells in the carotid body which
      may contribute to the maturation of hypoxic chemosensitivity. Furthermore, the
      presence A(1)-adenosine receptor mRNAs in cell bodies of the petrosal ganglion
      suggests that adenosine might also have an inhibitory role in hypoxic
      chemotransmission.

PMID- 10924670
TI  - Involvement of calmodulin-dependent protein kinase II in carbachol-induced
      rhythmic activity in the hippocampus of the rat.
AB  - The role of calcium and protein kinases in rhythmic activity induced by
      muscarinic receptor activation in the CA1 area in rat hippocampal slices was
      investigated. Extracellular recording showed that carbachol (20 microM) induced
      synchronized field potential activity with a dominant frequency of 7.39+/-0.68
      Hz. Pretreatment with the membrane permeable Ca(2+) chelator BAPTA-AM (50 microM)
      or with thapsigargin (1 microM), a compound which depletes intracellular calcium
      stores, reduced the dominant power of carbachol-induced theta-like activity by
      83% and 78%, respectively. Inhibition of calmodulin-dependent protein kinase II
      (CaMKII) by the cell permeable inhibitor KN-93 (10 microM) reduced the power of
      carbachol-induced theta-like activity by 80%. In contrast the protein kinase C
      (PKC) inhibitor calphostin C did not significantly (P>0.05) affect the effect of
      carbachol. Whole-cell recording indicated that KN-93 also blocked carbachol
      induced suppression of slow I(AHP) and strongly inhibited the carbachol-induced
      plateau potential. Our data suggest that activation of CaMKII by carbachol is
      crucial for local theta-like activity in the CA1 area of the rat hippocampus in
      vitro. Furthermore, involvement of CaMKII in carbachol-induced suppression of the
      slow I(AHP) and the induction of plateau potentials could play a role in the
      induction of theta-like rhythmic activity by carbachol.

PMID- 10924671
TI  - Antiepileptic efficacy of topiramate: assessment in two in vitro seizure models.
AB  - The antiepileptic efficacy of topiramate (TPM) has been demonstrated in both
      whole animal seizure models and clinical trials; however, there is no consensus
      concerning its mechanism of action. We determined first whether the antiepileptic
      effect of TPM generalized to in vitro seizure models. Epileptiform discharges,
      recorded extracellularly, were evoked by repeated tetanic stimulation of Schaffer
      collaterals and layer III association fibers in entorhinal cortex/hippocampus and
      piriform cortex slices, respectively. TPM was applied at concentrations of 20 or
      100 microM. Whole cell recordings were made from CA1 pyramidal neurons and the
      effect of TPM was assessed on a variety of intrinsic membrane properties
      including resting membrane potential, input resistance and postspike potentials.
      TPM (20 microM) was without effect in entorhinal cortex/hippocampus (N=6);
      however, 100 microM TPM decreased significantly the Coastline Burst Index from
      358.3+/-65.8 to 225. 5+/-77.1 (N=4), the frequency of spontaneous epileptiform
      discharges to 44.6+/-21.8 (N=5) and the duration of primary afterdischarge (PAD)
      to 65.9+/-10.1 (N=10) percent of control. In contrast, phenytoin (50 microM, N=7;
      100 microM, N=8) reduced PAD to 96.9+/-14. 8 and 86.5+/-17.3 percent of control,
      respectively. TPM (100 microM) did not reduce significantly the frequency of
      spontaneous discharges in piriform cortex (85.4+/-12.3 percent of control; N=5).
      TPM (100 microM) was without significant effect on intrinsic membrane properties
      in CA1 pyramidal neurons. Likely candidate mechanisms underlying the
      antiepileptic effect produced by TPM include enhancement of chloride-mediated
      GABA(A) currents and reduction of kainate and L-type calcium currents.

PMID- 10924672
TI  - The effect of topical insulin on the release of excitotoxic and other amino acids
      from the rat cerebral cortex during streptozotocin-induced hyperglycemic
      ischemia.
AB  - Insulin has been demonstrated to be neuroprotective in brain and spinal cord
      ischemia. The mechanism of neuroprotection may involve alterations in metabolism,
      protein synthesis or uptake of GABA by astrocytes. Conversely, hyperglycemia
      increases the extent of neurologic damage observed during ischemia/reperfusion.
      Diabetic patients are 2-4 times more likely to suffer a stroke as normoglycemic
      patients and they also have worsened neurologic outcome. Determining if insulin,
      which many diabetics already use as therapy, can be neuroprotective, would be a
      possible means of alleviating the detrimental outcome from diabetic stroke. This
      study looked at the relationship between topically administered insulin (1 mIU
      insulin/ml and 100 mIU insulin/ml) during a four vessel occlusion model of global
      ischemia and the release of amino acids, especially glutamate, from the cortex in
      streptozotocin (STZ)-treated rats. The rats were utilized either 5-7 days (ASTZ)
      or 4-6 weeks (CSTZ) after a single STZ injection. In the ASTZ animals both doses
      of insulin increased the amount of the excitotoxic amino acids, aspartate and
      glutamate, released during reperfusion and the higher dose also increased the
      levels of taurine and GABA during reperfusion. In the CSTZ animals, both doses of
      insulin increased the amount of excitotoxic amino acids during reperfusion and
      the lower dose increased GABA levels released during reperfusion. The differences
      between the ACTZ and CSTZ animals may be due to metabolic differences in the
      utilization of glucose. Insulin may act as a neuroprotectant by increasing
      extracellular GABA resulting in neuroinhibition.

PMID- 10924673
TI  - Lesions of the dorsal vagal complex abolish increases in meal size induced by
      NMDA receptor blockade.
AB  - Rats increase meal size and duration after intraperitoneal injection of MK-801, a
      non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. This effect
      depends upon intact vagal fibers, since the antagonist does not increase intake
      when visceral afferent and efferent pathways have been interrupted by bilateral
      subdiaphragmatic vagotomy. NMDA receptors have been demonstrated on vagal
      afferent fibers and on second-order neurons in the medial subnucleus of the
      solitary tract (NTS), the area postrema (AP), and the dorsal motor nucleus of the
      vagus. To determine whether neurons in these structures are crucial for NMDA
      receptor effects on feeding, we examined the effect of MK-801 on intake of 15%
      sucrose in rats with aspiration lesions of the AP and adjacent NTS. MK-801 (100
      microg/kg, i.p.) significantly increased sucrose intake in these lesioned rats
      compared to sham-lesioned rats (32.3+/-0.1 ml versus 23.3+/-0.1 ml, P<0.001).
      However, when the AP/NTS aspiration lesions were combined with bilateral
      electrolytic destruction of the medial NTS and the DMV, lesioned rats consumed
      nearly the same amount of sucrose after either saline or MK-801 (25.9+/-2.4 ml
      versus 24.3+/-3. 0 ml; P=0.687). By contrast, sham-lesioned controls ingested
      significantly more sucrose following MK-801 compared to saline (19. 8+/-1.0 ml
      versus 13.1+/-0.8 ml, P<0.001). These results suggest that an intact caudomedial
      NTS and/or DMV are necessary for increases in intake induced by NMDA receptor
      blockade. While the AP might participate in MK-801-induced enhancement of intake,
      it is not essential for this effect.

PMID- 10924674
TI  - Evidence for increased dorsal hippocampal adenosine release and metabolism during
      pharmacologically induced seizures in rats.
AB  - There is growing pharmacological evidence from several animal models of seizure
      disorder that adenosine possesses endogenous anticonvulsant activity. In order to
      further evaluate the role of adenosine in seizure activity, we monitored
      adenosine and its major biochemical metabolites inosine, xanthine, and
      hypoxanthine in the dorsal hippocampus by in vivo microdialysis before and during
      the induction of generalized seizures. Seizures were induced pharmacologically in
      groups of urethane-anesthetized rats by the administration of bicuculline (0.5
      mg/kg, i.v.), kainic acid (12.0 mg/kg, i.v.) or pentylenetetrazol (100-250 mg/kg,
      i.p). Seizure activity was monitored electrophysiologically from the dorsal
      hippocampus. Dialysate hippocampal purine levels increased during all three
      seizure types. The largest increases were for the adenosine metabolites
      hypoxanthine and inosine, with smaller increases observed for adenosine and
      xanthine. Intra-hippocampal perfusion with the adenosine deaminase inhibitor
      erythro-9-(2-hydroxy-3-nonyl-adenine, (EHNA, 300 microM), only slightly increased
      basal hippocampal adenosine. Guanosine levels in the hippocampus, a purine not
      directly related to adenosine metabolism, were unaffected by all treatments.
      These findings demonstrate that an increase in hippocampal adenosine release and
      metabolism is associated with seizure activity and support the hypothesis that
      the increased adenosine levels may attenuate hippocampal seizure activity,
      possibly by terminating ongoing seizures and altering the pattern of subsequent
      seizures.

PMID- 10924675
TI  - Electrophysiological properties of lumbosacral preganglionic neurons in the
      neonatal rat spinal cord.
AB  - The electrophysiological properties of parasympathetic preganglionic neurons
      (PGN) in L6 and S1 spinal cord slices from neonatal rats were studied using the
      patch clamp techniques. PGN were identified by retrograde axonal transport of a
      fluorescent dye (Fast Blue) injected intraperitoneally before the experiment. PGN
      in the intermediolateral region of the spinal cord were divided into two classes
      (tonic PGN and phasic PGN) on the basis of firing properties during prolonged
      (300 ms) depolarizing current pulses. Tonic neurons exhibited a prolonged
      discharge (average maximum: 5.6); whereas phasic PGN fired on average only 1.4
      spikes during depolarizing pulses. PGN were usually oval in shape. The mean long
      axis of tonic PGN (20.7+/-0.5 microm) was significantly (P<0.05) larger than that
      of phasic PGN (16.7+/-0.3 microm). Tonic and phasic PGN had similar resting
      membrane potentials, thresholds for spike activation, input resistances and
      action potential durations. The duration of the after-hyperpolarization (AHP) in
      tonic PGN (200.5+/-11.9 ms) was longer than in phasic PGN (137.6+/-9.8 ms). 4
      aminopyridine (4-AP, 0. 5 mM) reduced the threshold for spike activation in tonic
      and phasic PGN. 4-AP also unmasked tonic firing in phasic PGN (average maximum:
      5.5 spikes during 300 ms depolarizing current pulses) and increased firing
      frequency by 19% in tonic PGN. These data indicate that the different discharge
      patterns of parasympathetic PGN are dependent in part on differences in the
      expression of 4-AP-sensitive K(+) channels. The two types of PGN may provide an
      innervation to different targets in the pelvic viscera.

PMID- 10924676
TI  - Activation of hypothalamic insulin by serotonin is the primary event of the
      insulin-serotonin interaction involved in the control of feeding.
AB  - In previous experiments, we reported a close parallelism in the responses of both
      serotonin (5-HT) and insulin in the hypothalamic PVN-VMH region of freely-moving
      rats during feeding. Thus, hypothalamic 5-HT and insulin may participate,
      independently or in interaction, in the control of carbohydrate and fat
      ingestion. The precedence of the activation of one or the other substance
      remained to be investigated. In adult male Wistar rats, (a) dexfenfluramine was
      administered to the PVN-VMH region by reverse microdialysis (80 microM for 10
      min) while local insulin was assessed; (b) insulin was locally infused (400 mU
      for 10 min) through the tip of the dialysis probe while 5-HT was measured.
      Dexfenfluramine immediately increased 5-HT release, and also extracellular
      insulin levels (+102%). This activation of insulin by serotonin is actually a
      central effect since neither insulinemia nor glycemia were affected. Conversely,
      insulin enhanced 5-HT release (+81%), but only 45 min after the beginning of its
      infusion. Noradrenaline, dopamine and metabolites were slightly or not at all
      modified by insulin. These data demonstrate that an interaction does exist
      between insulin and 5-HT in the VMH-PVN area. Because of the delay of 5-HT
      response to insulin, an activation of the serotonergic system would be the causal
      event acting immediately on insulin, and not the contrary. Whatever the exact
      mechanism of this interaction, it seems to be a link in a larger cascade of
      events involving numerous neurotransmitters and peptides leading to the
      regulation of feeding.

PMID- 10924677
TI  - Effects of cholinergic depletion on neural activity in different laminae of the
      rat barrel cortex.
AB  - The purpose of these experiments was to determine the effects of cholinergic
      depletion on spontaneous and evoked activity of neurons in the different layers
      of the posteromedial barrel subfield (PMBSF) of the rat somatosensory cortex.
      Acetylcholine neurons in nucleus basalis of Meynert (NBM) were selectively
      lesioned with an immunotoxin (IT), 192 IgG-saporin. Spontaneous activity was
      significantly lower in layers II-III, Va, and VI in IT-injected animals compared
      to control animals. Evoked activity was significantly lower in layers II-III, IV,
      Vb, and VI of IT-injected animals compared to control animals. The largest
      difference was observed in layer Vb. Thus, cholinergic depletion causes
      significant changes in the magnitude of spontaneous and evoked activity but these
      differences are not completely in register with one another.

PMID- 10924678
TI  - Effects of check size on pattern reversal visual evoked magnetic field and
      potential.
AB  - The effects of different check sizes on the 100m component of pattern reversal
      visual evoked magnetic fields (VEF) and the P100 component of visual evoked
      potentials (VEP) in terms of latency, amplitude and source localization were
      analyzed. Half field stimuli with or without central occlusion with check sizes
      of 15', 30', 60', 90' and 180' of visual arc were given to 7 healthy subjects.
      VEF and VEP were recorded simultaneously. The effect of the check size on the
      peak latency of both 100m and P100 was significant (P<0.01, ANOVA). The latencies
      for the smaller checks were significantly longer than those for the larger
      checks. The effect of the check size on the amplitude of the 100m to the
      stimulation with central occlusion was significant (P<0.05, ANOVA), but was not
      to the stimulation without central occlusion. That is, the amplitudes for the
      smaller checks were significantly smaller than those for the larger checks when
      using the stimulation with central occlusion, but not the stimulation without
      central occlusion. The effect of the check size on the P100 amplitude was not
      significant to the stimulation with and without central occlusion. The equivalent
      current dipoles were located around the calcarine fissure and did not differ
      significantly in location with check size. In conclusion, check size
      significantly affects the latency and amplitude of the 100m and/or P100, but not
      the receptive areas for the stimulation.

PMID- 10924679
TI  - A single social defeat experience selectively stimulates the release of oxytocin,
      but not vasopressin, within the septal brain area of male rats.
AB  - The naturally occurring social conflict situation to be confronted with an
      aggressive dominant conspecific was used to study the effects of emotional stress
      on the release of oxytocin (OXT) and arginine vasopressin (AVP) within the
      mediolateral septum of the rat brain. Male rats were chronically implanted with a
      microdialysis probe into this brain area. Local release patterns of both, OXT and
      AVP were monitored in response to a 30 min social defeat. Social defeat caused a
      significant increase in the release of OXT (to 254%+/-43%, P<0.01). In contrast,
      the release of AVP was not affected. In a preliminary experiment, to assess the
      physiological significance of stress-induced intraseptal OXT release, a separate
      group of animals received the OXT receptor antagonist des-Gly
      NH(2)d(CH(2))(5)[Tyr(Me)(2)Thr(4)]OVT into the mediolateral septum via inverse
      microdialysis prior to and during the social defeat procedure. However, no
      difference could be observed in submissive freezing (passive coping) or in
      exploratory behavior (active coping) when compared to vehicle-treated animals,
      neither acutely nor 24 h after antagonist administration. Taken together, our
      results demonstrate that emotional stress activates the septal oxytocinergic, but
      not vasopressinergic, system. The physiological significance of intraseptally
      released OXT remains unclear and has to be elucidated in future studies.

PMID- 10924680
TI  - Spinal mechanisms underlying A-85380-induced effects on acute thermal pain.
AB  - Systemic administration of nicotinic receptor (nAChR) agonists is antinociceptive
      in models of acute pain whereas their intrathecal (i. t.) administration has been
      reported to be antinociceptive, nociceptive or without effect. It has been
      hypothesized that the action induced is dependent upon the subtype and location
      of the nAChR activated. In addition, there is considerable evidence that nAChR
      ligand-induced antinociception is mediated by other neurotransmitter systems via
      descending pathways from the brainstem to the spinal cord. The present study
      investigated the effects of i. t. and systemic administration of A-85380, a novel
      nAChR agonist, in the paw withdrawal model of acute thermal pain in the rat.
      Given i.t. , A-85380 (1 and 10 nmol/rat) decreased the latency to paw withdrawal
      by 2-4 s. This pronociception was accompanied by a spontaneous flinching
      behavior. Both of these effects were differentially blocked by i.t. pretreatment
      with the nAChR antagonists mecamylamine (10 nmol)>MLA (100 nmol)>DHbetaE (50%
      with 1000 nmol) but not by alpha-bungarotoxin (0% at 0.63 nmol). Given
      systemically, A-85380 (0.56 micromol/kg, i.p.) induced antinociception as
      indicated by an increased latency to paw withdrawal, an effect differentially
      altered by i.t. pretreatment with monoaminergic antagonists (100 nmol/rat). While
      mecamylamine and prazosin had no effect, scopolamine, methysergide and MDL 72222
      partially antagonized and idazoxan completely antagonized A-85380-induced
      antinociception. Finally, as measured by in vivo microdialysis, levels of 5-HT,
      but not NE, in the i.t. space of the lumber region of the spinal cord were
      significantly increased following the systemic administration of A-85380.
      Together these data suggest that the nociceptive properties of spinally
      administered nAChR agents are not mediated by either an alpha(4)beta(2) or an
      alpha(7) subtype nAChR, whereas the antinociceptive properties of systemically
      administered nAChR agents are mediated by descending noradrenergic, serotonergic
      and muscarinic inhibitory pathways.

PMID- 10924681
TI  - Basal and cocaine-induced opioid receptor gene expression in the rat CNS analyzed
      by competitive reverse transcription PCR.
AB  - The basal mRNA levels of kappa and mu opioid receptors, as well as their
      regulation after 'binge' cocaine administration, were determined with competitive
      reverse transcription polymerase chain reaction (RT-PCR) in brain regions of male
      Sprague-Dawley rats. The procedure proved to be a reliable method to quantify the
      relative opioid receptor gene expression. The highest basal mRNA levels for the
      kappa opioid receptor were found in the nucleus accumbens and hypothalamus,
      whereas the highest basal mRNA expression for the mu opioid receptor was observed
      in the hypothalamus. Rats were separately treated with 'binge' (three hourly
      injections) cocaine HCl (45 mg/kg/day i.p.) or saline (1 ml/kg i.p.) for 2 days.
      A significant down-regulation of the kappa opioid receptor mRNA was detected in
      the nucleus accumbens. The mu opioid receptor mRNA was not affected. The data
      suggest a selective effect on kappa receptor expression in the nucleus accumbens
      as a consequence of 'binge' cocaine use.

PMID- 10924682
TI  - Effects of adenosine agonists and an antagonist on excitatory transmitter release
      from the ischemic rabbit hippocampus.
AB  - The purpose of this study was to determine the effects of adenosine agonists and
      an antagonist on ischemia-induced extracellular glutamate concentrations in an
      animal model of transient cerebral ischemia using in vivo cerebral microdialysis.
      Fifty New Zealand white rabbits were randomly assigned to one of five groups
      (normothermia, hypothermia, cyclopentyladenosine (CPA), theophylline, or
      propentofylline). Microdialysis probes were stereotactically placed in the dorsal
      hippocampus. Twenty minutes before the onset of ischemia, either 1 mg/kg CPA, 5
      mg/kg propentofylline, or 20 mg/kg theophylline were administered intravenously.
      Esophageal temperature was maintained at 38 degrees C, except in the hypothermic
      animals, which were cooled to 30 degrees C throughout the entire experiment. Two
      12-min periods of cerebral ischemia, separated by a 105-min interval of
      reperfusion, were produced by inflating a neck tourniquet. High-performance
      liquid chromatography was used to determine the glutamate concentration in the
      microdialysate. There were no significant increases in glutamate concentrations
      during the first ischemic period in any of the five groups. During the second
      ischemic episode, glutamate concentrations in the normothermic group peaked at
      levels approximately three times higher than the initial values. A similar
      pattern of changes in glutamate concentrations was observed in the CPA,
      propentofylline, and theophylline groups. In the hypothermic group, the
      concentrations of glutamate remained at baseline levels during the entire
      experiment. Contrary to expectations, neither the adenosine agonists (CPA,
      propentofylline) nor the antagonist (theophylline) had any effect on
      extracellular glutamate concentrations in the peri-ischemic period. Although
      adenosine and its analogs may be cerebroprotective agents, their mechanism of
      action is not fully understood. The data derived from this study indicates that
      the acute administration of such agents had no effect on ischemia-induced
      glutamate release within the hippocampus under these experimental conditions.
      Based on these results, further work is needed to compare in vivo versus in vitro
      experimental results in acute and long-term treatment studies with adenosine
      receptor agonists and antagonists.

PMID- 10924683
TI  - Alteration of intracellular pH and activity of CA3-pyramidal cells in guinea pig
      hippocampal slices by inhibition of transmembrane acid extrusion.
AB  - Transmembrane acid extruders, such as electroneutral operating Na(+)/H(+)
      exchangers (NHE) and Na(+)-dependent Cl(-)/HCO(3)(-)-exchangers (NCHE) are
      essential for the maintenance and regulation of cell volume and intracellular pH
      (pH(i)). Both of them are hypothesised to be closely linked to the control of
      excitability. To get further information about the relation of neuronal pH(i) and
      activity of cortical neurones we investigated the effect of NHE- and/or NCHE
      inhibition on (i) spontaneous action potentials and epileptiform burst-activity
      (induced by bicuculline-methiodide, caffeine or 4-aminopyridine) and (ii) on
      pH(i) of CA3-neurones. NHE-inhibition by amiloride (0.25-0.5 mM) or its more
      potent derivative dimethylamiloride (50 microM) and NCHE-inhibition by 4,4'
      diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 0.25-0.5 mM) induced a
      biphasic alteration of neuronal activity: an initial, up to 30 min lasting,
      increase in frequency of action potentials and bursts preceded a growing and
      partially reversible suppression of neuronal activity. In BCECF-loaded neurones
      the pH(i), however, continuously decreased during either amiloride- or DIDS
      treatment and reached its steady-state (DeltapH(i) up to 0.3 pH-units) when the
      neuronal activity was markedly suppressed. Combined treatment with amiloride (0.5
      mM) and DIDS (0.5 mM) or treatment with harmaline alone (0.25-0.5 mM), which also
      continuously acidified neurones via inhibition of an amiloride-insensitive NHE
      subtype, induced a monophasic and partially reversible suppression of neuronal
      activity. As an initial excitatory period failed to occur during combined
      NHE/NCHE-inhibition we speculate that its occurrence during amiloride- or DIDS
      treatment resulted rather from disturbances in volume- than in pH(i)-regulation.
      The powerful inhibitory and anticonvulsive properties of NHE- and NCHE
      inhibitors, however, very likely based upon intracellular acidification - as
      derived from our previous findings that a moderate increase in intracellular free
      protons is sufficient to reduce membrane excitability of CA3-neurones.

PMID- 10924684
TI  - Age-related synaptic changes in sensorimotor cortex of the Brown Norway X fischer
      344 rat.
AB  - Investigations of age-related changes in synapse density have yielded
      contradictory conclusions. The goal of the present study was to determine whether
      there is a significant decline in the number of cortical synapses in old age.
      Therefore, brains from 10-, 15-, and 32-month-old Brown Norway X Fischer 344 rats
      were prepared for electron microscopy and synapses were counted in a
      stereotaxically-identified region of sensorimotor cortex. Within this cortical
      area, synapses were counted in layers 2 and 4 and the data have been presented
      both as number of synapses per volume of neuropil and as the ratio of synapses
      per neuron. Results indicated that there was a decline in synapse density between
      15 and 32 months in layer 2, but not in layer 4. This decline was significant not
      only for total synapses, but also for subcategories of synapses when classified
      by presynaptic features or postsynaptic element. Specifically, there was a
      significant decline in presumptive inhibitory synaptic terminals, i.e., those
      containing nonround synaptic vesicles, as well as a significant decline in
      synapses that contact dendritic spines.

PMID- 10924685
TI  - Electrical stimulation of the insular cortex induces flavor-preferences in rats.
AB  - The present study examined the role of the Insular cortex (IC) in flavor-guided
      behavior. For that purpose, a flavored stimulus was paired with delayed
      electrical stimulation of this region. In addition, a standard operant task
      explored the involvement of the IC in a prefrontal self-stimulation reward
      circuit. The results showed strong preferences for the flavored stimulus
      previously paired to the Insular stimulation, in a discriminative free choice
      test. However, the operant task revealed a failure to induce IC self-stimulation,
      suggesting that flavor preferences elicited by electrical stimulation of the IC
      are not due to activation of the prefrontal-stimulation reward circuit. These
      results are discussed in terms of the Insular Cortex as critical in processing
      visceral stimulus, hedonic valence and/or food-reward incentive learning.

PMID- 10924686
TI  - Agmatine suppresses nitric oxide production in microglia.
AB  - We investigated the effect of agmatine, an arginine metabolite synthesized in the
      brain, in cultured microglia obtained from neonatal rat cerebral cortex. Agmatine
      (1-300 microM) did not affect viability of cultured microglia. Activation of
      microglia by lipopolysaccharide (LPS, 1 microg/ml) caused the expression of
      inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO)
      assessed as the accumulation of nitrite in the culture supernatants. Agmatine had
      no effect on the expression of iNOS, but significantly suppressed the LPS-induced
      NO production in a concentration-dependent manner. Agmatine was also effective in
      suppressing the production of NO induced by a combination of interferon-gamma
      (500 U/ml) and amyloid beta protein (10 microM). In co-cultures of rat cortical
      neurons and microglia, LPS caused significant loss of neuron viability. The LPS
      neurotoxicity was not observed in the absence of microglia, and was completely
      blocked by the NOS inhibitor diphenyleneiodoium chloride. The neuronal death
      induced by microglia-derived NO was significantly attenuated by the presence of
      agmatine. These results suggest that agmatine works to protect neurons by
      inhibiting the production of NO in microglia.

PMID- 10924687
TI  - Mesopontine contribution to the expression of active 'twitch' sleep in
      decerebrate week-old rats.
AB  - Myoclonic twitching is a ubiquitous feature of infant behavior that has been used
      as an index of active sleep. Although the active sleep of infants differs in some
      ways from the REM sleep of adults, their marked similarities have led many to
      view them them as homologous behavioral states. Recently, however, this view has
      been challenged. One avenue for resolving this issue entails examination of the
      neural substrates of active sleep. If the neural substrates of active sleep were
      found to be similar to those of REM sleep, then this would support the view that
      the two states are homologous. Therefore, in the present study, decerebrations
      were performed in the pons and midbrain to determine whether the mesopontine
      region is important for the expression of active sleep in infants, just as it is
      for the expression of REM sleep in adults. It was found that, in comparison to
      controls, caudal pontine decerebrations reduced myoclonic twitching by 76%,
      rostral pontine decerebrations reduced twitching by 40%, and midbrain
      transections had no significant effect on twitching. Moreover, analysis of the
      temporal organization of twitching indicated that pontine decerebrations
      predominantly affected high-frequency twitching while leaving unaffected the low
      frequency twitching that is thought to be contributed by local spinal circuits at
      this age. These results indicate that the mesopontine region plays a central role
      in the expression of active sleep in infant rats.

PMID- 10924688
TI  - Estrogen modulates responses of striatal dopamine neurons to MPP(+): evaluations
      using in vitro and in vivo techniques.
AB  - In vitro superfusion and in vivo electrochemistry were used to investigate the
      role of estrogen in modulating MPP(+)-induced dopamine output in the corpus
      striatum and nucleus accumbens of ovariectomized female rats. For in vitro
      superfusion experiments, dopamine and dihydroxyphenylacetic acid release were
      determined using HPLC with electrochemical detection from superfusion of corpus
      striatum fragments with Kreb's ringer phosphate buffer pulsed with MPP(+) alone
      or MPP(+) with estrogen. The in vivo electrochemistry experiments recorded the
      dopamine signal from carbon fiber microelectrodes stereotaxically passed through
      the corpus striatum and nucleus accumbens. Dopamine release was stimulated by
      pressure ejection of MPP(+) alone or in combination with estrogen through glass
      micropipettes fastened to the electrodes. Dopamine output from superfusion
      chambers which received infusion of MPP(+) with estrogen showed significantly
      lower output of dopamine compared with chambers which received MPP(+) alone.
      Outputs of dihydroxyphenylacetic acid did not increase following MPP(+)
      infusions. Data from the electrochemistry experiments demonstrated that estrogen
      significantly reduced both the amplitude and clearance rates of the MPP(+)-evoked
      dopamine signal in both the corpus striatum and nucleus accumbens. Results of
      this study demonstrate that: (1) MPP(+) evokes striatal dopamine release and this
      effect is significantly reduced in the presence of estrogen as determined by both
      in vivo electrochemistry and in vitro superfusion: (2) similar, albeit attenuated
      effects are observed in the nucleus accumbens as determined with in vivo
      electrochemistry; (3) estrogen acts to inhibit the clearance of dopamine in both
      the striatum and nucleus accumbens; and (4) estrogen may function as a
      neuroprotectant by reducing the uptake of neurotoxin into dopaminergic neurons.

PMID- 10924689
TI  - Metabotropic glutamate receptor subtypes are differentially expressed after
      transient cerebral ischemia without, during and after tolerance induction in the
      gerbil hippocampus.
AB  - Postischemic delayed neuronal death (DND) of hippocampal CA1 neurons can be
      prevented by a preconditioning sublethal ischemic stimulus. To check for possible
      participation of metabotropic glutamate receptors (mGluRs) in neuronal death or
      survival, we analyzed postischemic protein expression of subtypes 1b and 5 of
      group I mGluRs, which are thought to exert neurotoxic effects after pathological
      activation due to ischemia, and subtypes 2 and 3 of group II mGluRs, which in
      contrast are thought to be neuroprotective in this state, respectively.
      Therefore, three groups of gerbils with reperfusion intervals between 8 h and 4
      days (n=5 each) were investigated: one group was subjected to 5 min ischemia,
      resulting in DND of CA1 neurons, a second group to a tolerance inducing 2.5 min
      period of ischemia and a third group to 5 min ischemia after prior tolerance
      induction. The major finding was a transient postischemic reduction of mGluR1b
      and 5 expression in the ischemic tolerant CA1 subfield at 8 h. This
      downregulation of neurotoxic mGluRs may indicate a contribution to the survival
      of highly vulnerable CA1 neurons in the ischemic tolerant state.

PMID- 10924690
TI  - Nocistatin inhibits food intake in rats.
AB  - Nocistatin, a product of the same precursor as nociceptin/orphanin FQ (N/OFQ),
      has been shown to antagonize effects of N/OFQ. N/OFQ stimulates feeding, most
      probably by inhibiting activation of neurons containing oxytocin (OT) and
      vasopressin (VP), peptides considered as satiety factors, and implicated in the
      development of conditioned taste aversion (CTA). The present study was designed
      to investigate whether intracerebroventricularly (ICV) injected nocistatin (a)
      affects deprivation- and N/OFQ-induced feeding, (b) causes CTA, and (c) induces
      activation of hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, as
      well as OT and VP neurons present in these regions. C-Fos immunohistochemistry
      was used as a marker of cellular activation. Nocistatin (1-3 nmol) significantly
      reduced food intake in deprived rats during the first and second hour post
      injection. Doses of 1-3 nmol suppressed N/OFQ-induced feeding. Nocistatin at the
      highest (3 nmol) dose did not cause CTA. It also did not affect activation of the
      PVN or SON. In nocistatin-treated animals, the percentage of Fos-positive OT and
      VP neurons was similar to controls. We conclude that nocistatin antagonizes the
      influence of N/OFQ on feeding and suppresses deprivation-induced food consumption
      through mechanisms other than aversion. Nocistatin does not, however, activate
      the PVN or SON. It does not exert its effects via VP or OT neurons.

PMID- 10924691
TI  - Mice lacking in gp91 phox subunit of NAD(P)H oxidase showed glomus cell
      [Ca(2+)](i) and respiratory responses to hypoxia.
AB  - The hypothesis that NAD(P)H oxidase may serve as an oxygen sensor was tested
      using the mice deficient (knock-out) in gp91phox subunit of NAD(P)H oxidase
      enzyme complex and compared with wild-type (C57BL/6J) strain measuring the
      ventilatory and glomus cell intracellular calcium ([Ca(2+)](i)) responses of
      carotid body to hypoxia. The hypoxic ventilatory responses as well as the
      [Ca(2+)](i) were preserved in the NAD(P)H oxidase knock-out mice. NAD(P)H
      oxidase, though a major source of oxygen radical production, is not the oxygen
      sensor in mice carotid body.

PMID- 10924692
TI  - Time course of inwardly rectifying K(+) current reduction in glial cells
      surrounding ischemic brain lesions.
AB  - K(+) currents of activated glial cells surrounding ischemic infarcts are
      investigated using acutely dissociated cells from the periinfarct area after
      permanent middle cerebral artery occlusion in rats. Inwardly rectifying K(+)
      currents (K(IR)) were markedly reduced in cells neighboring infarcts with maximal
      alteration at day 3 after infarct followed by a partial recovery. This reduction
      of glial K(IR) currents may contribute to the functional disturbances in the
      periinfarct area.

PMID- 10924693
TI  - Does endogenous 5-HT mediate spontaneous rhythmic activity in chemoreceptor
      clusters of rat carotid body?
AB  - Spontaneous voltage fluctuations often occurred during perforated-patch
      recordings from clustered rat carotid body (CB) chemoreceptors in vitro. This
      activity sometimes appeared as rhythmic-like spikes, when cluster size exceeded
      approximately 20 cells. Spike discharge could be augmented or induced by hypoxia
      or 5-HT (2-10 microM) application, and inhibited by the 5-HT receptor blocker,
      ketanserin (50-100 microM). Thus, endogenous 5-HT may contribute to spontaneous
      firing within CB receptor clusters via autocrine/paracrine mechanisms.

PMID- 10924694
TI  - R(+)-8-OH-DPAT, a selective 5-HT(1A) receptor agonist, attenuated amphetamine
      induced dopamine synthesis in rat striatum, but not nucleus accumbens or medial
      prefrontal cortex.
AB  - R(+)-8-OH-DPAT (0.05, but not 0.025, 0.1, 1 mg/kg), a 5-HT(1A) receptor agonist,
      decreased l-3,4-dihydroxyphenylalanine (DOPA) accumulation in rat striatum
      following NSD-1015, an l-aromatic amino acid decarboxylase inhibitor. Amphetamine
      (1 mg/kg) increased striatal DOPA accumulation, an effect attenuated by R(+)-8-OH
      DPAT (0.05 mg/kg). However, both amphetamine (1 mg/kg) and R(+)-8-OH-DPAT (0.05
      mg/kg) decreased cortical DOPA accumulation; there were no additional decreases
      from their combination. Neither amphetamine (1 mg/kg), R(+)-8-OH-DPAT (0.05
      mg/kg), or the combination, significantly affected DOPA accumulation in the
      nucleus accumbens. The significance of and possible mechanisms for these findings
      are discussed.

PMID- 10924695
TI  - Morphological evidence for a vestibulo-thalamo-striatal pathway via the
      parafascicular nucleus in the rat.
AB  - We observed by anterograde and retrograde tracing techniques that projection
      fibers originating from the medial vestibular nucleus (MVe) of the rat terminated
      in the dorsal two-thirds of the lateral part of the parafascicular thalamic
      nucleus (PF), where neurons sending their axons to the dorsolateral part of the
      striatum existed. It was further revealed that the vestibular fibers made
      asymmetrical synaptic contacts mainly with dendrites and additionally with soma
      of the striatum-projecting PF neurons. These data suggest that output signals
      from the MVe may be transmitted disynaptically to the striatal neurons via the PF
      neurons.

PMID- 10924696
TI  - Gene-dosing effect and persistence of reduction in ischemic brain injury in mice
      lacking inducible nitric oxide synthase.
AB  - We investigated whether the reduction in ischemic brain injury in inducible
      nitric oxide synthase (iNOS) null mice is related to the iNOS gene copy number,
      and whether such protection is long lasting. The middle cerebral artery (MCA) was
      occluded in heterozygous (+/-) and homozygous (-/-) iNOS null mice, as well as in
      wild-type littermates (iNOS +/+). Four days after MCA occlusion, total infarct
      volume was reduced by 29% in iNOS -/- mice (n=6; P<0.05) and by 14% in iNOS+/
      mice (n=8; P<0.05), compared to iNOS +/+ (n=8). Ten days after MCA occlusion,
      total infarct volume was still reduced in iNOS +/- (-14%) and -/- mice (-21%;
      P<0.05 from iNOS +/+; n=8/group). These data indicate that the reduction in
      infarct volume is greater in iNOS -/- than in iNOS +/- mice and that the effect
      is stable in time. We conclude that the reduction in ischemic damage conferred by
      iNOS deletion exhibits a gene-dosing effect and that the protection is long
      lasting.

PMID- 10924697
TI  - Increased synapsin I immunoreactivity during long-term potentiation in rat
      hippocampus.
AB  - The level of synapsin I, a synaptic vesicle protein and marker for synaptic
      activation, was studied 8 h after long-term potentiation (LTP) induction in rat
      hippocampus in vivo. Quantitative immunohistochemical analysis revealed that
      synapsin I increased significantly in the molecular layer of the dentate gyrus
      and the stratum lucidum of CA3, suggesting activation of the granule cells by
      synaptic input to the dentate gyrus, and persistent enhancement of glutamate
      release from the axon terminals of the dentate granule cells.

PMID- 10924698
TI  - Activation by nicotine of striatal neurons receiving excitatory input from the
      substantia nigra via dopamine release.
AB  - An electrophysiological study was performed to elucidate the role of nicotinic
      receptors in the striatal neurons in chloral hydrate-anesthetized rats. The
      effects of microiontophoretic application of nicotine and other drugs were
      examined on the caudate nucleus (CN) neurons activated monosynaptically by
      stimulation of the substantia nigra pars compacta (SN). Application of nicotine
      facilitated spontaneous firing. The nicotine-induced firing of the CN neurons was
      inhibited by concomitant application of domperidone or hexamethonium. These
      findings suggested that nicotine enhances dopamine release from the SN-derived
      dopaminergic nerve terminals by activating the neurons via D2 receptors.

PMID- 10924699
TI  - Regulation of c-fos gene expression by lipopolysaccharide and cycloheximide in C6
      rat glioma cells.
AB  - The effect of lipopolysaccharide (LPS) on the expression of immediate early
      genes, such as c-fos and c-jun, was examined in C6 rat glioma cells. LPS (1
      microg/ml) alone did not affect c-fos mRNA level. LPS, however, transiently
      increased c-jun mRNA level. Cycloheximide (CHX, 20 microM), a protein synthesis
      inhibitor, alone caused increases of c-fos and c-jun mRNA levels. LPS showed a
      potentiating effect in the regulation of c-fos mRNA level, whereas LPS showed an
      additive action for the regulation of CHX-induced c-jun mRNA expression. To
      determine if CREB and mitogen-activated protein kinases (MAPKs) are involved in
      the regulation of c-fos mRNA expression by LPS and CHX, Western blot was carried
      out using the phosphorylated form of antibodies against ERK, JNK, p38, and CREB.
      LPS transiently increased the phosphorylation of p38-MAPK and CREB. In addition,
      LPS alone elevated phosphorylation of ERK (p44/p42) MAPK in a time-dependent
      manner. Furthermore, LPS plus CHX enhanced phosphorylation of ERK, p38, and CREB
      in a synergistic manner. Our results suggest that the phosphorylation of ERK,
      p38, and CREB may be involved in the regulation of synergistic c-fos mRNA
      expression induced by LPS plus CHX in C6 rat glioma cells.

PMID- 10924700
TI  - Dopamine uptake by mouse neuroblastoma N1E-115 cells stably expressing human
      dopamine transporter is differentially inhibited by anti-idiotypic ab2beta
      antibodies mimicking the configuration of cocaine.
AB  - We have successfully constructed a mouse neuronal N1E-115 cell line stably
      expressing a fully functional human dopamine transporter (hDAT). Previous studies
      in our laboratory have produced several anti-idiotypic Ab2beta antibodies that
      mimic the configuration of the cocaine molecule at their antigen-combining site.
      In the present study, we observed that some anti-idiotypic Ab2beta antibodies
      inhibited dopamine uptake by the hDAT-transfected line. Each antibody showed a
      different level of inhibition (between 40% and 90%). These findings suggest that
      the internal images of these antibodies can be used as analog peptides that may
      compete with cocaine for its binding site on the transporter but not impair
      dopamine uptake as much as cocaine does.

PMID- 10924701
TI  - Increase of bcl-2 protein in neuronal dendritic processes of cerebral cortex and
      hippocampus by the antiparkinsonian drugs, talipexole and pramipexole.
AB  - Treatment of rats for 4 days with the antiparkinsonian drugs, talipexole and
      pramipexole, markedly increased Bcl-2 immunoreactivity in neuronal dendritic
      processes in both cerebral cortex and hippocampus, but treatment for 1 day with
      either of these drugs did not. Repeated administration of talipexole or
      pramipexole may have neuroprotective effect in neurodegenerative disorders.

PMID- 10924702
TI  - Permanent and temporary inactivation of the hippocampus impairs T-maze footshock
      avoidance acquisition and retention.
AB  - The hippocampus is widely recognized as playing an important role in learning and
      memory. Lesions of the hippocampus can disrupt spatial navigational learning and
      memory and injection of drugs into the hippocampus can affect both spatial
      navigational and nonspatial tasks. In the current studies we tested the effects
      of bilateral of electrolytic lesions and reversible inactivation of the
      hippocampus on acquisition and retention of T-maze footshock avoidance
      conditioning. Electrolytic lesions, which destroyed 31+/-0.04% of the
      hippocampus, significantly impaired acquisition and retention for T-maze
      footshock avoidance. No differences were found in motivation to avoid shock, open
      field activity, or foot shock sensitivity between lesion and control groups.
      Temporary inactivation of the hippocampus with lidocaine administered immediately
      before training disrupted acquisition and retention for T-maze footshock
      avoidance. Temporary hippocampal inactivation performed just prior to retention
      testing and post-training inactivation in mice trained to first avoidance had no
      effect on retention. However, temporary post-training inactivation in
      'undertrained' (enough trials to remember 1 week later if treated with saline,
      but not allowed to make the avoidance response) mice impaired retention. The
      current findings indicate that the hippocampus plays an important role in
      learning and memory processing in the aversive T-maze paradigm.

PMID- 10924703
TI  - More cerebellar granule cells following prenatal low-dose X-irradiation.
AB  - It was the aim of this study to estimating and comparing the total number of
      granule and Purkinje cells in the cerebellum of 180-day-old mice following a
      prenatal low-dose X-irradiation (50 cGy) at day 13 of gestation. Using the
      optical fractionator we found an expected, significant decrease of the total
      number of Purkinje cells (-21.1%; P=0.041) and a surprising, significant increase
      of the total number of granule cells (+23.1%; P=0.026) if comparing prenatally
      irradiated with sham-irradiated mice. The possible molecular basis of these
      seemingly paradoxical results is discussed.

PMID- 10924704
TI  - Adult ovary transfer counteracts the callosal enlargement resulting from
      prepubertal ovariectomy.
AB  - The rat corpus callosum (CC) is larger in males than females, and is sensitive to
      hormone manipulations during development. Previous research found that, in rats,
      CC sensitivity to testosterone ended by postnatal day 8 (P8). In contrast, more
      recent findings demonstrated that CC responsivity to ovarian hormones continued
      at least through P70. The current experiment extends these findings by showing
      that the female callosum is still sensitive to ovarian hormones as late as P130,
      well into adulthood.

PMID- 10924705
TI  - Vasomotor hyporeactivity in the anterior cerebral artery during motor activation
      in Huntington's disease patients.
AB  - This experiment used functional transcranial Doppler ultrasonography to
      demonstrate that blood flow velocity in the anterior cerebral artery is
      hyporeactive in Huntington's disease (HD) patients during maze testing (P<0.05).
      These vascular changes are due to tracing, as opposed to problem solving,
      components of the maze task. Using logistic regression, the reactivity of the ACA
      during activation is able to categorize patients as being either gene negative,
      or positive, for HD (P=0.0007). The possible role that nitric oxide/peroxynitrite
      may play in this phenomena is discussed.

PMID- 10924706
TI  - The ratio of striatal D1 to muscarinic receptors changes in aging rats housed in
      an enriched environment.
AB  - The enriched environment (EC) causes morphological plasticity in striatal cells
      that express D1 and D2 receptors. We used radioligand binding assays to examine
      whether EC produces plasticity in striatal receptor density and receptor density
      ratios. After 30 days of EC, 2-year-old rats had a higher ratio of D1 to
      muscarinic receptors in striatum relative to singly housed rats. Assays also
      showed trends for a greater ratio of D1 to cannabinoid receptors and a greater
      density of D1 receptors in striatum after EC. D2 receptor density was unaffected
      by the EC condition.

PMID- 10924707
TI  - GABA(A) and GABA(B) receptors modulating basal and footshock-induced nitric oxide
      releases in rat prefrontal cortex.
AB  - Using an in vivo brain microdialysis technique, we measured extracellular levels
      of nitric oxide (NO) metabolites (NO(x)(-)) in the medial prefrontal cortex
      (mPFC) upon perfusion of gamma-aminobutyric acid (GABA) receptor antagonists as
      well as agonists, and also examined the effects of GABA receptor agonists on mild
      intermittent footshock-induced NO releases in the mPFC in conscious rats.
      Perfusion of either bicuculline methiodide, a GABA(A) receptor antagonist, or
      saclofen, a GABA(B) receptor antagonist, through a microdialysis probe resulted
      in dose-dependent increases in NO(x)(-) levels. Higher-dose perfusion of either
      muscimol (50 microM), a GABA(A) receptor agonist, or baclofen (250 microM), a
      GABA(B) receptor agonist resulted in a significant decrease in NO(x)(-) levels.
      The elevated levels of NO(x)(-) after mild intermittent footshock were attenuated
      by perfusion of either muscimol (10 microM) or baclofen (50 microM), either of
      which alone did not affect basal NO(x)(-) levels. These findings are likely to
      provide helpful clues to our understanding of the inhibitory modulation of basal
      and footshock-induced NO metabolites releases by GABA(A) and GABA(B) receptors in
      the mPFC.

PMID- 10924708
TI  - Localization of 5-HT(6) receptors at the plasma membrane of neuronal cilia in the
      rat brain.
AB  - 5-HT(6) receptor-like immunoreactivity has been previously found in association
      with both neuronal dendrites and cilia in the striatum, nucleus accumbens,
      olfactory tubercle and islands of Calleja of the rat brain. Using immunogold pre
      embedding immunocytochemical techniques to investigate the subcellular
      localization of 5-HT(6) receptor-like immunoreactivity in cilia, we showed that
      immunogold particles were associated with their plasma membrane, and not with
      microtubules. This membrane localization is consistent with a possible
      physiological role, which is still unknown, of these receptors.

PMID- 10924709
TI  - Immobility accompanies the antinociception mediated by the rostral ventromedial
      medulla of the rat.
AB  - The rostral ventromedial medulla (RVM) is part of a descending pain modulatory
      system that runs from the periaqueductal gray (PAG) to the spinal cord. The
      objective of the present study was to determine whether the antinociception
      mediated by the RVM is associated with locomotor changes as has been reported for
      the PAG [42]. Kainate (4, 20, or 40 pmol), morphine (1, 5, or 10 microg), or
      saline (0.2 or 0. 5 microl) was injected into the RVM and locomotion and
      nociception assessed. Microinjections of kainate and morphine that produced
      antinociception almost invariably inhibited locomotor activity. In some rats this
      immobility consisted of no movements when placed in the center of the open field
      chamber. These data are consistent with the immobility and antinociception
      produced by activation of the ventrolateral PAG and indicate that the descending
      ventrolateral PAG/RVM system integrates a behavioral response of which
      antinociception is only one component.

PMID- 10924710
TI  - Temporary changes of the AP-1 transcription factor binding activity in the gerbil
      hippocampus after transient global ischemia, and ischemic tolerance induction.
AB  - Global forebrain ischemia of 5-min duration results in delayed neuronal death
      (DND) of CA1 neurons in the gerbil hippocampus. DND can be prevented by a
      preconditioning sublethal ischemic stimulus (2. 5 min), a phenomenon, known as
      ischemic tolerance induction. Striking evidence exists for the involvement of
      regulatory transcription factors encoded by immediate early genes (IEGs) in the
      fate of CA1 neurons. Here, we investigated by electrophoretic mobility shift
      assay (EMSA) the postischemic changes of the DNA binding activity of the
      Activator Protein-1 (AP-1) transcription factor complex after preconditioning,
      lethal ischemia, and after acquisition of an ischemic tolerant state. A short
      duration peak of AP-1 binding activity at 3 h of reperfusion was a hallmark of
      ischemic tolerance induction. The kinetics of this activation profile, i.e. the
      rapid linear increase between 1 and 3 h and a similar rapid decline at 6 or 12 h
      of reperfusion are prominent within the CA1 and CA3 region of all ischemic groups
      which are designated for neuronal survival. No changes in the c-Jun and ATF-2
      immunoreactivity were observed in the CA1 region, however an increase in only c
      Jun immunoreactivity occurred in concordance with the elevation of AP-1 binding
      in the CA3 region. The results clearly demonstrate a differential regulation of
      AP-1 binding activity in CA1 during and after acquisition of an ischemic tolerant
      state in contrast to ischemia leading to neuronal death. The early peak at 3 h of
      reperfusion in AP-1 binding affinity observed in the single 2.5 min and the
      ischemic tolerant groups suggests a protective role of early AP-1 activation,
      whereas failure of this initial activation may contribute to DND. Our data
      furthermore suggest, that elevation of the AP-1 binding activity in the CA1 and
      CA3 regions underlies a different regulatory mechanism in the gerbil hippocampus
      after ischemic stress.

PMID- 10924711
TI  - Dynamic changes of NADH fluorescence images and NADH content during spreading
      depression in the cerebral cortex of gerbils.
AB  - To elucidate the changes in the mitochondrial redox state during spreading
      depression (SD), tissue NADH content was measured in 20 anesthetized gerbils by
      the enzymatic cycling assay in a small cortical region (0.30+/-0.07 mg) where the
      direct-current (DC)-potential was measured. Sequential imaging of NADH
      fluorescence with a CCD camera and continuous monitoring of DC-potential and
      regional CBF were also performed in another 5 gerbils. Biphasic fluorescence
      waves propagating at the rate of 3 mm/min were observed using the CCD camera. An
      initial narrow (1.6+/-0.4 mm) wave, which showed a modest increase in
      fluorescence (108+/-6.4%), was observed simultaneously with the onset of negative
      DC-deflection. During depolarization, CBF was unchanged and tissue NADH content
      increased to 25.3+/-7.9 micromol/kg brain, which was higher than the value in the
      sham-control (11.0+/-2.5 micromol/kg brain). At 30 s after the deflection, a
      subsequent wide (7.0+/-2.1 mm) wave, which showed a moderate decrease in
      fluorescence (87.1+/-5.7%), was observed simultaneously with the increase in CBF
      and repolarization in DC-potential. Then NADH fluorescence recovered along with
      normalization of CBF at 152.2+/-38.6 s after the onset of DC-deflection. Tissue
      NADH concentration sampled at 120 s after the deflection was 11.6+/-4.6
      micromol/kg brain. Since NADH fluorescence is absorbed by hemoglobin, the initial
      increase and subsequent decrease in fluorescence seem to have been induced by
      increases in NADH content and CBF, respectively. These findings indicate that the
      mitochondrial redox state transiently inclines to the reduction side synchronous
      to the onset of DC-deflection and that it normalizes within 120 s after
      deflection.

PMID- 10924713
TI  - Intestinal absorption of triglyceride and cholesterol. Dietary and
      pharmacological inhibition to reduce cardiovascular risk.
AB  - Triglycerides and cholesterol are important biological lipids, and their
      excessive intake in the diet is relevant to the development of two prevalent
      cardiovascular risk factors, obesity and hypercholesterolemia. Because most
      lipids are essentially water-insoluble molecules, their transport within and
      absorption from the aqueous medium of intestinal contents is rather complex. This
      takes place in a series of orderly and interrelated steps, including
      emulsification, hydrolysis by specific esterases, micellar transport, mucosal
      absorption, re-synthesis of parent molecules in enterocytes, and assembly with
      apolipoproteins and other molecules to form chylomicrons, the secretory product
      of intestinal cells. Many of these processes, however, are not well characterized
      at the molecular level. While in health the intestinal absorption of
      triglycerides is very efficient, the same does not apply to cholesterol
      absorption. Besides being generally inefficient, cholesterol absorption is highly
      variable, with a between-subject variability that depends in part on genetic
      factors and an intra-individual variability, which may be modulated by
      physiological and dietary conditions. All of the sequential steps in intestinal
      lipid absorption can be interfered with by dietary components or drugs and thus
      are potential therapeutic targets for inducing a controlled malabsorption of
      triglyceride, useful in the treatment of obesity, or for rendering cholesterol
      absorption even more inefficient in an attempt to lower blood cholesterol levels.
      Nevertheless, intestinally derived cholesterol available to the liver exerts
      complex feedback regulation on whole-body cholesterol homeostasis that limits the
      efficacy of cholesterol absorption inhibitors to lower blood cholesterol. This
      review focuses first on present knowledge of the physiology of intestinal fat
      absorption, necessary to understand the ways to manipulate it in order to obtain
      the desired effects on dietary triglyceride and cholesterol disposition. The
      second part discusses old, present and future ways, both dietary and
      pharmacological. of interfering with cholesterol and triglyceride absorption to
      reduce blood cholesterol and energy acquisition, respectively.

PMID- 10924712
TI  - S-nitroso-l-cysteine releases norepinephrine in rat spinal synaptosomes.
AB  - Although nitric oxide (NO) participates in development of hypersensitivity states
      in the spinal cord thought to underlie chronic pain, it also participates in
      analgesia produced by various drugs. In rats with a hypersensitivity state
      following peripheral nerve injury, spinal administration of an NO donor or l
      cysteine alone produced no effect, whereas their combination, which yields s
      nitroso-l-cysteine (SNC) powerfully reduced hypersensitivity. In the current
      study, we examined the ability of SNC to stimulate release of a known spinal
      analgesic neurotransmitter, norepinephrine (NE), as a possible mechanism of
      analgesic action of NO in the spinal cord. SNC (but not the NO donor alone or
      decomposed SNC) produced a concentration-dependent release of NE from rat spinal
      cord synaptosomes. The d-isomer of SNC was less potent than the l-isomer, and the
      effect of SNC was partially blocked by l-, but not d-leucine, implicating an
      interaction with the l-amino acid transporter. SNC-induced NE release was
      partially Na(+) dependent, but largely Ca(2+) independent. NE uptake inhibitors
      partially antagonized the effect of SNC, but guanylate cyclase inhibitors were
      without effect. These data are therefore consistent with NO stimulating NE
      release in the spinal cord via reaction with thiol containing compounds, such as
      cysteine, entry into NE terminals via active transport, and production of both
      exocytotic and carrier mediated release.

PMID- 10924714
TI  - Effects of age, gender, and lifestyle factors on plasma apolipoprotein A-IV
      concentrations.
AB  - Apolipoprotein (apo) A-IV is a protein component of triglyceride (TG)-rich
      lipoproteins and high density lipoproteins (HDL). Plasma apo A-IV levels were
      measured by immunoelectrophoresis and these values were related to other
      biological variables in 723 middle aged and elderly men and women (more than 90%
      of them were Caucasian) prior to participation in a lifestyle modification
      program. Apo A-IV may play an important function in regulating lipid absorption,
      reverse cholesterol transport, and food intake. The data are consistent with the
      following concepts: (1) apo A-IV levels are significantly and positively
      correlated with age (r = 0.159, P < 0.05) in all subjects, with plasma apo A-I
      levels in both men (r = 0.194, P < 0.001) and women (r = 0.213, P < 0.001), and
      with apo E (r=0.111, P<0.05) and TG levels (r =0.120, P <0.05) in men; (2) apo A
      IV levels are inversely correlated with body mass index (r = 0.170, P <0.05) in
      women; (3) female subjects on hormone replacement therapy have significantly
      lower plasma apo A-IV levels (by 4.1%, P < 0.05) than normal controls; (4)
      diabetic subjects have significantly higher apo A-IV levels (by 21%, P < 0.01)
      than normal subjects; (5) there is no significant effect of smoking, alcohol
      intake, and apo A-IV-1/2 genotype on apo A-IV levels. The data indicate that
      plasma apo A-IV levels are significantly affected by age, diabetes, and hormone
      replacement therapy.

PMID- 10924715
TI  - C3H apoE(-/-) mice have less atherosclerosis than C57BL apoE(-/-) mice despite
      having a more atherogenic serum lipid profile.
AB  - Wild-type C57BL mice are known to be susceptible to diet-induced atherosclerosis,
      whilst C3H mice are resistant. We investigated the effect of these background
      strains on the hyperlipidaemia and atherosclerosis that develops in mice
      deficient in apolipoprotein E (apoE(-/-)). Male and female apoE(-/-) mice on
      C3H/HeNHsd (C3H) and C57BL/6J (C57) backgrounds were fed atherogenic Western diet
      for 12 weeks. Serum cholesterol and triglyceride concentrations were measured and
      atherosclerosis quantified in the aortic sinus. C3H apoE(-/-) mice fed normal
      diet had 1.5 2 fold higher serum cholesterol levels than C57 apoE(-/-) mice and 4
      5 fold higher serum triglyceride concentrations. Feeding Western diet caused a 4
      5 fold increase in serum cholesterol in all mice, but levels of triglyceride were
      either attenuated or were unaffected in C3H apoE(-/-) and C57 apoE(-/-) mice,
      respectively. C3H apoE(-/-) mice had approximately 2 fold higher serum
      cholesterol and 4 fold higher triglyceride concentrations than the C57 apoE(-/-)
      mice throughout the study. Serum triglyceride concentrations were 35-108% higher
      in male C3H apoE(-/-) than female C3H apoE(-/-) mice. Most of the lipids were
      present in the very low density lipoprotein (VLDL)/chylomicron fraction in both
      strains of mice whether they were fed normal or Western diet. Notwithstanding the
      lower plasma lipid concentrations, atherosclerotic lesion areas were more than 2
      fold larger in C57 apoE(-/-) than in C3H apoE(-/-) mice (males 68 +/- 11 x 10(3)
      vs 30 +/- 6 x 10(3) females 102 +/- 12 x 10(3) vs 41 +/- 8 x 10(3) microm2. mean
      +/- SEM).

PMID- 10924716
TI  - Reduced mildly oxidized LDL in young female athletes.
AB  - We investigated the effect of physical activity and sports participation on LDL
      oxidation in vivo and on lipid risk factors in 183 teenage girls (9-15 years): 64
      gymnasts, 61 runners, and 58 controls. Oxidized LDL was measured as baseline
      levels of conjugated dienes in LDL lipids (ox-LDL). The gymnasts had a 15% lower
      ratio of LDL conjugated dienes to LDL cholesterol (ox-LDL:LDL ratio, P = 0.0052)
      compared to controls, and the difference persisted when the body mass index was
      included as a covariate (ANCOVA, P = 0.013). Also, the gymnasts had a 12% higher
      ratio of HDL cholesterol to total cholesterol than the controls (ANCOVA, P =
      0.046). There were no differences in the other common lipid risk factors between
      the groups. The ox-LDL:LDL ratio correlated negatively with HDL cholesterol (r = 
      0.23, P=0.0021) and with physical activity METs (multiples of resting metabolic
      rate) (r = -0.21, P=0.0040). Our study strengthens the evidence that the
      atherogenic risk is influenced favourably by physical exercise and sporting
      activities as early as in adolescents. This risk reduction is associated with
      lower mildly oxidized LDL in adolescent girls.

PMID- 10924717
TI  - Response to balloon injury is vascular bed specific: a consequence of de novo
      vessel structure?
AB  - Relative contributions of remodelling and neointimal hyperplasia to restenosis
      after coronary angioplasty have been inferred from studies using iliofemoral
      arteries, despite differences in structure/function and smooth muscle cell
      lineage. We compared the response to balloon overstretch injury of coronary
      arteries (C, n = 16) and similar sized branches of the iliac arteries (I, n = 18)
      using preinjury vessel diameter (P). inflated balloon size in vivo (B) and the
      manufacturer predicted inflated size (M) to examine arterial compliance, as well
      as resulting injury and morphology in perfusion fixed vessels. Despite similar
      degrees of oversizing (M/P) in the coronary and iliac arteries (C, 1.44 +/- 0.04;
      I, 1.51 +/- 0.02), the compliance to overstretch (B-P/M-P) was significantly
      greater in the coronary than the iliac arteries (C, 0.71 +/- 0.05; I, 0.51 +/-
      0.03) (P <0.05) and was associated with a higher injury score (C, 1.64 +/- 0.31;
      I, 0.39 +/- 0.18 P < 0.05)--only 5/18 iliac vessels had rupture of the IEL
      compared with 13/16 in the coronary bed. In a subgroup of animals whose vessels
      (C:n = 7; I:n = 8) were perfusion fixed 28 days after injury, coronary arteries
      had greater intimal area (C:1.03 +/- 0.42; I:0.10 +/- 0.03 mm2, P < 0.05) but
      larger luminal area (C:1.61 +/- 0.71; 1:0.76 +/- 0.51, P < 0.05) due to greater
      area within EEL (C:3.38 +/- 0.49;1:] .49 +/- 0.54, P < 0.05) or less inward
      remodelling. The injuries resulting from similar strategies of balloon
      overstretch in the coronary and the iliac arteries are different and affect
      healing responses--iliac arteries remodel more while coronary arteries develop
      more intimal hyperplasia. These results indicate that caution is warranted when
      extrapolating results from the iliac to the coronary artery when investigating
      restenosis after angioplasty.

PMID- 10924718
TI  - The relationship between employment grade and plasma fibrinogen level among
      Japanese male employees. YKKJ Research Group.
AB  - Plasma fibrinogen is an important risk factor for cardiovascular disease, and is
      associated with socioeconomic status in Europe and the United States. We
      evaluated whether the relationship between socioeconomic status and plasma
      fibrinogen level exists in Japanese male employees, and whether this relationship
      is independent of other correlates of plasma fibrinogen. This cross-sectional
      study was conducted on full-time male employees aged 20-58 in a metal-products
      factory between April 1996 and March 1997. Altogether 4375 employees (92.9%)
      participated. Low employment grade and low educational background were associated
      with increased age-adjusted plasma fibrinogen level. Adjusting for body mass
      index, waist to hip ratio, height, smoking habit, alcohol consumption, physical
      activity at leisure and systolic blood pressure did not attenuate these
      associations much. Adjusting for white blood cell count and hemoglobin Alc
      reduced the associations of both employment grade and educational background with
      plasma fibrinogen level, nevertheless these relationships remained significant.

PMID- 10924719
TI  - Plasma total homocysteine levels in postmenopausal women with unstable coronary
      artery disease.
AB  - An elevated plasma total homocysteine (tHcy) level is considered a risk factor
      for coronary artery disease (CAD), but the relationship between plasma tHcy and
      well-defined CAD in women is still unclear. Plasma tHcy concentrations and the
      covariates serum folate, vitamin B12, and creatinine were analysed in 157
      angiographically examined postmenopausal women with unstable CAD and in 101
      healthy controls. At coronary angiography, 16% had normal vessels and 84% had
      coronary atherosclerosis. Mean plasma tHcy concentration (micromol/l, 95%
      confidence interval) did not differ in patients compared to controls (13.1 (12.3
      13.8) vs. 12.5 (11.6-13.5)) or in patients with or without coronary
      atherosclerosis (13.3 (12.4-14.1) vs. 12.0 (10.8-13.2)). A trend to an increasing
      plasma tHcy with increasing degree of coronary atherosclerosis was attenuated
      after adjustment for age and the previous mentioned covariates. Odds ratio for
      the risk of coronary artery disease and coronary atherosclerosis in
      hyperhomocysteinemic patients (> or =90th percentile in controls) was
      approximately 3. However, the confidence interval included unity in half of the
      groups and the significance was therefore difficult to judge. Receiver operating
      characteristics showed age to be the only variable with a significant
      discriminatory ability regarding the presence of coronary atherosclerosis (area
      0.77). Mild hyperhomocysteinemia seems not to be related to the risk of unstable
      CAD in postmenopausal women. The trend towards higher plasma tHcy with increasing
      degree of coronary atherosclerosis may be a marker of the disease. In future
      studies adjustment for age and the other three covariates should be considered.

PMID- 10924720
TI  - Multiple cytokines regulate the expression of extracellular superoxide dismutase
      in human vascular smooth muscle cells.
AB  - Oxygen free radicals as well as immunological reactions have been suggested to
      play important roles in atherogenesis and other pathological processes of the
      blood vessel wall. We have previously shown that the vascular wall contains
      exceptionally large amounts of extracellular superoxide dismutase (EC-SOD) and
      that the enzyme is produced and secreted to the extracellular space by the smooth
      muscle cells. In this work, we studied the influence of inflammatory cytokines on
      vascular smooth muscle cell expression of EC-SOD, the mitochondrial manganese
      superoxide dismutase (Mn-SOD) and the cytosolic copper zinc superoxide dismutase
      (CuZn-SOD). The expression of EC-SOD was up-regulated by interferon-gamma (IFN
      gamma) and interleukin 4 (IL-4). and was down-regulated by tumor necrosis factor
      alpha (TNF-alpha). The ratio between the maximal stimulation and depression
      observed was around 20-fold. The responses were slow and developed over periods
      of several days. The Mn-SOD activity was strongly up-regulated by TNF-alpha and
      IL-1alpha and moderately by IFN-gamma. The CuZn-SOD activity of the smooth muscle
      cells was not significantly influenced by any of the cytokines. The findings
      suggest that large changes in the SOD isoenzymes might occur in vascular
      diseases, significantly altering the susceptibility of the vascular wall to
      adverse effects of the superoxide radical.

PMID- 10924721
TI  - The V73M mutation in the hepatic lipase gene is associated with elevated
      cholesterol levels in four Dutch pedigrees with familial combined hyperlipidemia.
AB  - Familial combined hyperlipidemia (FCHL) is a heritable lipid disorder
      characterized by multiple lipoprotein phenotypes within a single family.
      Previously, we have shown an increased incidence of mutations in the LPL gene
      which was associated with elevated levels of very low density lipoprotein (VLDL)
      and decreased levels of high density lipoprotein among the families studied. Now,
      we report the results of our study on the hepatic lipase gene. We found the HL
      V73M variant to be present in four FCHL families. By means of a pedigree-based
      maximum log-likelihood method we analyzed the effect of this variant on the lipid
      levels in these families. Carriers of the HL V73M variant revealed significantly
      higher levels of total cholesterol (P < 0.01) and apoB (P <0.01). These findings
      show that the HL V73M mutant explains another part of the variability in the
      phenotype observed among FCHL family members, compared with mutations in the LPL
      gene. Family analysis shows that in these FCHL families, carriers of mutations in
      the LPL or HL genes have an increased risk for FCHL compared with their non
      carrier relatives.

PMID- 10924722
TI  - Quantification of human plasma phospholipid transfer protein (PLTP): relationship
      between PLTP mass and phospholipid transfer activity.
AB  - A sensitive sandwich-type enzyme-linked immunosorbent assay (ELISA) for human
      plasma phospholipid transfer protein (PLTP) has been developed using a monoclonal
      capture antibody and a polyclonal detection antibody. The ELISA allows for the
      accurate quantification of PLTP in the range of 25-250 ng PLTP/assay. Using the
      ELISA, the mean plasma PLTP concentration in a Finnish population sample (n =
      159) was determined to be 15.6 +/- 5.1 mg/l, the values ranging from 2.30 to 33.4
      mg/l. PLTP mass correlated positively with HDL-cholesterol (r = 0.36, P < 0.001),
      apoA-I (r = 0.37, P < 0.001), apoA-II (r = 0.20, P < 0.05), Lp(A-I) (r=0.26,
      P=0.001) and Lp(A-I/A-II) particles (r=0.34, P<0.001), and negatively with body
      mass index (BMI) (r = -0.28, P < 0.001) and serum triacylglycerol (TG)
      concentration (r = -0.34, P < 0.001). PLTP mass did not correlate with
      phospholipid transfer activity as measured with a radiometric assay. The specific
      activity of PLTP, i.e. phospholipid transfer activity divided by PLTP mass,
      correlated positively with plasma TG concentration (r=0.568, P<0.001), BMI
      (r=0.45, P<0.001), apoB (r = 0.45, P < 0.001). total cholesterol (r=0.42, P <
      0.001), LDL-cholesterol (r = 0.34, P < 0.001) and age (r = 0.36, P < 0.001), and
      negatively with HDL-cholesterol (r= -0.33, P < 0.001), Lp(A-I) (r= -0.21, P <
      0.01) as well as Lp(A-I/A-II) particles (r = -0.32, P < 0.001). When both PLTP
      mass and phospholipid transfer activity were adjusted for plasma TG
      concentration, a significant positive correlation was revealed (partial
      correlation, r = 0.31, P < 0.001). The results suggest that PLTP mass and
      phospholipid transfer activity are strongly modulated by plasma lipoprotein
      composition: PLTP mass correlates positively with parameters reflecting plasma
      high density lipoprotein (HDL) levels, but the protein appears to be most active
      in subjects displaying high TG concentration.

PMID- 10924723
TI  - Mononuclear cell adhesion to collagen ex vivo is related to pulse pressure in
      elderly subjects.
AB  - Mononuclear cells and platelets are intimately involved in the pathogenesis and
      complications of cardiovascular disease. Platelet activation has been reported in
      hypertension, though the activation-state of monocytes has received less
      attention. In this study the adhesiveness of monocytes and platelets was assessed
      and any relationship between the adhesive properties of these cellular elements
      and plasma levels of soluble adhesion molecules and blood pressure parameters
      determined. Fifty six elderly volunteers, of whom 32 were classified hypertensive
      (daytime SBP > or = 135 mmHg), underwent 24 h blood pressure monitoring,
      assessment of monocyte and platelet adhesion and measurement of the plasma
      soluble adhesion molecules ICAM-1, L-selectin, E-selectin and vWF. In the elderly
      hypertensive subjects, monocyte adhesion to collagen coated (P < 0.05) and tissue
      culture plastic microwells (P < 0.05) was significantly elevated and circulating
      levels of soluble ICAM-1 (P < 0.01) and soluble E-selectin (P < 0.05) were
      significantly raised compared to their normotensive counterparts. A significant
      correlation was found to exist between monocyte adhesion to collagen and daytime
      pulse pressure (r = 0.39, P < 0.01) and also between plasma levels of soluble E
      selectin and clinic DBP (r = 0.40, P < 0.001). The increased monocyte adhesion
      witnessed in hypertensive subjects and with increasing pulse pressure may
      contribute to the increased risk of cardiovascular disease in hypertension.
      Whether this increased adhesiveness is a property of the monocytes. or reflects
      endothelial cell activation, remains to be determined.

PMID- 10924724
TI  - Chylomicron remnants potentiate phenylephrine-induced contractions of rat aorta
      by an endothelium-dependent mechanism.
AB  - The effects of chylomicron remnants on endothelium-dependent contraction of rat
      aorta were studied in vitro. Chylomicron remnant particles were prepared in vivo
      from male Wistar rats and were incubated with aortic rings for 45 min before
      concentration contraction response curves were constructed to phenylephrine. Both
      native and oxidised chylomicron remnants significantly increased vessel
      sensitivity to this agonist. Oxidised chylomicron remnants also significantly
      increased the maximum response. This potentiation was abolished by endothelial
      removal, but was still evident in the presence of Nomega-nitro-L-arginine, with
      or without cyclo (D-alpha-aspartyl-L-prolyl-D-valyl-L-leucyl-D-tryptophyl) (BQ
      123), indomethacin or superoxide dismutase. The study demonstrates, for the first
      time, that lipoprotein particles of dietary origin potentiate vascular
      contractions. This effect is endothelium-dependent, but is not due to inhibition
      of basal nitric oxide production or to stimulation of endothelin, superoxide or a
      cyclo-oxygenase-derived product.

PMID- 10924725
TI  - Lysophosphatidylcholine induces apoptotic and non-apoptotic death in vascular
      smooth muscle cells: in comparison with oxidized LDL.
AB  - Oxidized low-density lipoprotein (oxLDL) plays a key role in the development of
      atherogenesis, partly by causing injury to vascular cells. However, different
      preparations of LDL, methods of oxidation, and/or active components often produce
      cellular effects of various degrees. To explore the quantitative relationship
      between dose and level of oxidation of the oxLDL utilized, we employed
      combinations of different levels of oxidation and concentrations of oxLDL to
      induce cell death in cultured vascular smooth muscle cells (VSMC). We also
      examined the effect of lysophosphatidylcholine (lysoPC), a putative active
      component of oxLDL, on VSMCs by determining, in parallel with a cytotoxicity test
      (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay), DNA
      fragmentation ([3H]thymidine release), and flow cytometric analyses. We found
      that oxLDL caused cytotoxicity in an oxidative level- and dose-dependent manner,
      lysoPC also caused dose-dependent cytotoxicity with or without serum.
      Fragmentation of DNA was observed in both oxLDL- and lysoPC-treated VSMCs.
      Furthermore, lysoPC-induced DNA ladder was also demonstrated by gel
      electrophoresis at a concentration of 25 micromol/l or higher. Flow cytometric
      analysis yielded similar results for oxLDL- and lysoPC-treated VSMC; namely, an
      accumulation in the fraction of cells in G(0)/G(1) phase with a reciprocal change
      in S-phase fraction. Membrane phosphatidylserine exposure, detected by annexin V
      staining, provided additional evidence that lysoPC induced significant apoptosis
      in VSMC. Taken together, the degree of oxLDL-induced cytotoxicity/apoptosis of
      VSMC depended on combined effects of oxLDL concentration and oxidative level.
      Moreover, lysoPC also elicited a dose-dependent apoptosis in addition to
      cytotoxicity.

PMID- 10924726
TI  - Prospective randomised cross-over comparison of three LDL-apheresis systems in
      statin pretreated patients with familial hypercholesterolaemia.
AB  - Various LDL-apheresis systems have gained wider clinical acceptance in recent
      years to treat patients with severe familial hypercholesterolaemia, in particular
      in patients with coronary artery disease. For each single device data on efficacy
      have been provided, but up to now no comparative analysis including the novel
      direct adsorption of lipoproteins from whole blood has been reported. This
      prospectively designed cross-over comparison of three commercially available LDL
      apheresis systems (immunoadsorption, IMAL; dextran sulphate adsorption, DSA;
      direct adsorption of lipoproteins, DALI) was performed in eight patients with
      homozygous (n = 3) and heterozygous (n = 5) familial hypercholesterolaemia.
      Removal of atherogenic lipoproteins was highly effective in all systems, for LDL
      cholesterol in particular: DSA: - 84.3 +/- 6.2%; IMAL: -82.1 +/- 8.3%; DALI: 
      76.6 +/- 7.2% (P < 0.05 as compared DALI versus IMAL and DSA). A reduction in
      Lp(a) of about 63% was achieved by each device. Loss in HDL-cholesterol was
      highest with IMAL (-21.3 +/- 4.9%, P < 0.05) as compared to the other two
      treatment modalities. DSA decreased HDL-cholesterol by - 10.4 +/- 6.1% and the
      DALI system by -12.7 +/- 5.0%. Remarkable differences were found for the removal
      of fibrinogen (DSA: -29.8 +/- 14.7%, (P < 0.05 versus DALI/IMAL); IMAL: -21.4 +/-
      10.1% (P < 0.05 versus DALI); DALI: -14.8 +/- 8.0%). The shortest duration for
      treatment was achieved by the DALI system (135 +/- 20 min, P < 0.05 versus IMAL
      (195 +/- 20 min) and DSA (187 +/- 29 min)). No side effects were recorded in the
      total of 96 treatments performed during the study. Long-term observations have
      yet to prove whether these differences in efficacy may be of clinical relevance.

PMID- 10924727
TI  - Ultrasound determined carotid and femoral atherosclerosis in Lithuanian and
      Swedish men: the LiVicordia study.
AB  - Coronary heart disease mortality is four times higher in Lithuanian compared to
      Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear
      transducer) and staff, we compared the amount of atherosclerosis in carotid and
      femoral arteries in 100 randomly sampled 50-year-old men in each of the cities
      Vilnius, Lithuania and Linkoping, Sweden. Atherosclerotic plaques were more
      abundant in Vilnius men compared to Linkoping men (53 versus 28% in the common
      carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both).
      Plaques were thicker and more extended in arteries of Vilnius men, and an
      ultrasound atherosclerosis score was higher in both carotid and femoral arteries
      (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the
      common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid
      artery was higher in Vilnius men (P<0.001). In a linear regression model of the
      pooled material, after adjustment for city was made, smoking, systolic blood
      pressure, low density lipoprotein cholesterol and beta-carotene (inversely)
      significantly contributed to a high total ultrasound score (r2 = 0.32). These
      findings show that the higher coronary mortality noted in Lithuanian men goes
      together with a higher prevalence of early peripheral atherosclerosis.

PMID- 10924728
TI  - Taq1B CETP polymorphism, plasma CETP, lipoproteins, apolipoproteins and sex
      differences in a Jewish population sample characterized by low HDL-cholesterol.
AB  - Mean high-density lipoprotein cholesterol (HDL-C) concentrations are low in the
      Jewish population of Israel. With this in mind we assessed the association of the
      Taq1B CETP polymorphism, plasma CETP mass and plasma lipid, lipoprotein and
      apolipoprotein concentrations in a sample of 884 Jerusalem residents aged 28-32.
      The allele frequency (0.435 +/- 0.017(S.E.)) is similar to that reported
      elsewhere. There was a strong (apparently codominant) association of the Taq1 B
      allele with plasma CETP in both sexes, and an inverse association with HDL-C and
      apo A-1, significant in women and undiminished upon adjustment for plasma CETP.
      There was evidence in this population for an admixture of two plasma CETP
      distributions, with 9% belonging to a distribution with the higher mean, pointing
      to a possible major gene effect. Mean plasma CETP was higher in women than men.
      Plasma CETP was inversely associated with HDL-C in men but not in women (P< 0.05
      for the sex difference, multivariate analysis), inversely related to the HDL
      C/apo A-1 ratio in men and positively related in women (P < 0.005 for the sex
      difference), and was positively associated with total cholesterol (TC) and low
      density lipoprotein cholesterol in both sexes, and with the TC/HDL-C ratio and
      apo B in men alone. The sex differences may reflect dissimilarities in the
      regulatory function of CETP in lipid exchange. The absence of an unusual allele
      frequency of the Taq1B CETP polymorphism and its relatively modest association
      with HDL-C argue against an important role for this or strongly linked sites in
      determining the low population levels of HDL-C in Israel.

PMID- 10924729
TI  - Plasma homocysteine and its association with carotid intimal-medial wall
      thickness and prevalent coronary heart disease: NHLBI Family Heart Study.
AB  - Mildly elevated plasma total homocysteine (tHcy) levels have been associated with
      increased risk of coronary heart disease (CHD). Carotid artery intimal-medial
      wall thickening is a predictor of cardiovascular disease and has been previously
      shown to be positively associated with plasma tHcy in studies of asymptomatic
      subjects. In the current study we examined 1467 subjects with regard to their
      fasting plasma tHcy levels and intimal-medial wall thickness as measured by B
      mode ultrasound and early onset CHD. The results showed that there is a
      significant positive association between plasma tHcy levels and carotid-artery
      wall thickness in participants 55 years or older even after the tHcy levels are
      adjusted for age, smoking and anti-hypertensive medication. The direction and
      magnitude of the relationship is similar although the result was not
      statistically significant in younger participants ( < 55 years). Early onset CHD
      at any age was not significantly different across the tHcy quintiles. The lack of
      an association of tHcy and CHD in the presence of a positive association with
      intimal-medial wall thickening may be a reflection of increased statistical power
      of quantitative versus qualitative traits. We conclude that the present finding
      of a positive association between tHcy and intimal-medial wall thickness
      strengthens the in vitro finding of the stimulating effect of homocysteine on
      vascular smooth muscle cell growth. Vascular smooth muscle cell proliferation may
      be an important mechanism through which mildly elevated plasma tHcy promotes
      atherosclerosis.

PMID- 10924730
TI  - FH-Freiburg: a novel missense mutation (C317Y) in growth factor repeat A of the
      low density lipoprotein receptor gene in a German patient with homozygous
      familial hypercholesterolemia.
AB  - We describe the characterization of a novel mutation in the low density
      lipoprotein receptor (LDL-R) gene in a patient with true homozygous familial
      hypercholesterolemia (FH). The combined use of denaturing gradient gel
      electrophoresis (DGGE) and sequencing of genomic DNA revealed a guanine to
      adenine base substitution at nucleotide position 1013 of the LDL-R cDNA. This
      point mutation results in a change from cysteine to tyrosine at amino acid
      residue 317 of repeat A of the epidermal growth factor (EGF) precursor homology
      domain. Binding, uptake and degradation of iodinated LDL in skin fibroblasts from
      the homozygous patient were less than 10% of normal. In contrast, binding, uptake
      and degradation of iodinated VLDL was reduced by only 60, 30, and 38%,
      respectively. Incubation of the patient's fibroblasts in the presence of
      cholesterol diminished the residual binding of VLDL by 50%, suggesting that the
      loss of the highly conserved cysteine at position 317 results in a LDL-R that
      fails to bind LDL, but retains some ability to bind VLDL by interacting with the
      apolipoprotein E. Both parents were heterozygous for the C317Y mutation.
      Interestingly, however, the father presented with markedly elevated levels of
      triglycerides and VLDL cholesterol, whereas his LDL cholesterol was unexpectedly
      low. The mother of the index patient had only slightly elevated LDL cholesterol.
      These observations testify to the biological complexity of genotype-environment
      interactions in individuals carrying mutations at the LDL-R locus and indicate
      that genetic analysis importantly complements the clinical and biochemical
      diagnosis of patients with hyperlipidemia.

PMID- 10924731
TI  - Redox status of plasma homocysteine and other plasma thiols in stroke patients.
AB  - Despite the growing evidence that plasma homocysteine is a cardiovascular risk
      factor, the mechanism behind the vascular injuries is still unknown. Studies are
      difficult as a result of the fact that little is known about the formation of
      different homocysteine species in vivo. Since extracellular glutathione and
      cysteine may influence the formation of different homocysteine species, we have
      in the present study investigated the different fractions of homocysteine and
      their relation to the different fractions of glutathione and cysteine in stroke
      patients and control subjects. We found a ratio of about 32-33% between reduced
      and total plasma glutathione concentrations and 2.6 3.0% between reduced and
      total plasma cysteine concentrations both in patients and in healthy control
      subjects. We noted an elevated concentration of total plasma homocysteine in
      stroke patients, but no difference in the ratio between reduced and total plasma
      homocysteine concentrations in patients and control subjects (mean value 1.20 and
      1.10%, respectively). However, in a subgroup of patients with higher
      concentrations of total plasma homocysteine, we observed a significantly lower
      ratio of reduced to total plasma homocysteine compared to a subgroup of patients
      with lower concentration of total plasma homocysteine. A low reduced/total ratio
      of plasma homocysteine in combination with elevated plasma homocysteine
      concentrations might reflect an increased pro-oxidant activity in plasma from
      these patients. Thus, increased pro-oxidant activity in plasma might be one
      factor, besides genetic and nutritional factors, that could explain
      hyperhomocysteinemia. Since substantial evidence indicates that progression of
      atherosclerosis is related to enhanced pro-oxidant activity, the premature
      vascular disease associated with increased plasma homocysteine concentration
      might be as a result of increased pro-oxidant activity and the elevated plasma
      homocysteine concentration may only reflect the increased oxidative stress.

PMID- 10924732
TI  - Ascorbic acid supplementation does not lower plasma lipoprotein(a)
      concentrations.
AB  - Elevated plasma concentrations of lipoprotein(a) (Lp[a]) are associated with
      premature coronary heart disease (CHD). Lp(a) is a lipoprotein particle
      consisting of low-density lipoprotein (LDL) with apolipoprotein (apo) (a)
      attached to the apo B-100 component of LDL. It has been hypothesized that
      ascorbic acid supplementation may reduce plasma levels of Lp(a). The purpose of
      this study was to determine whether ascorbic acid supplementation at a dose of 1
      g/day would lower plasma concentrations of Lp(a) when studied in a randomized,
      placebo-controlled, blinded fashion. One hundred and one healthy men and women
      ranging in age from 20 to 69 years were studied for 8 months. Lp(a) values at
      baseline for the placebo group (n = 52) and the ascorbic acid supplemented group
      (n = 49) were 0.026 and 0.033 g/l, respectively. The 8-month concentrations were
      0.027 g/l (placebo) and 0.038 g/l (supplemented group). None of these values were
      significantly different from each other. In addition, no difference in plasma
      Lp(a) concentration was seen between the placebo and supplemented groups when
      only subjects with an initial Lp(a) value of > or = 0.050 g/l were analyzed. Our
      data indicate that plasma Lp(a) concentrations are not significantly affected by
      ascorbic acid supplementation in healthy human subjects.

PMID- 10924733
TI  - Statin treatment increases the sialic acid content of LDL in hypercholesterolemic
      patients.
AB  - Low density lipoprotein (LDL) with low sialic acid content has been reported to
      cause intracellular cholesterol accumulation, and therefore desialylation has
      been proposed to be an atherogenic modification of LDL. However, it is not known
      whether hypolipidemic treatment has any effect on LDL sialylation. Accordingly,
      we investigated the sialic acid/apolipoprotein (apo) B ratio of total LDL and its
      subfractions in 26 moderately hypercholesterolemic patients at baseline and after
      treatment with statins for 2-3 months. Cholesterol and triglyceride levels were
      reduced in all apo B-containing lipoproteins, including all LDL subfractions,
      while the sialic acid ratio was increased in total LDL and in all its
      subfractions. Cholesterol concentrations and sialic acid ratios were inversely
      correlated in light and dense LDL subfractions both before and during statin
      treatment, and the greater the decrease in cholesterol and apo B contents of
      dense LDL, the higher was the increase in its sialic acid ratio. Furthermore, the
      lower the baseline sialic acid ratio of dense LDL, the greater was the reduction
      in its lipid and apo B concentrations. In conclusion, inhibition of cholesterol
      synthesis by statin treatment increased sialic acid/apo B ratio in LDL
      proportionately to the decrease of LDL apo B and cholesterol.

PMID- 10924734
TI  - LDL physical properties, lipoprotein and Lp(a) levels in acromegalic patients.
      Effects of octreotide therapy. Italian Multicenter Octreotide Study Group.
AB  - High vascular morbidity and mortality is associated with acromegaly. The aim of
      the present study was to assess the effects of octreotide therapy on several
      known cardiovascular risk factors and to correlate them with octreotide-induced
      hormonal changes. Lipid levels, LDL particle size distribution as evaluated by
      single vertical spin density gradient ultracentrifugation, apolipoproteins AI and
      B, lipoprotein (a) [Lp(a)] concentrations and apo(a) phenotypes were evaluated in
      20 non-diabetic acromegalic patients (6 M, 14 F), with normal thyroid, adrenal
      and gonadal function, aged 29-66 years. Normal subjects (20), matched for age,
      sex and BMI served as control for lipid variables. Acromegalic patients were
      characterized by lower HDL cholesterol (and apoA-I) and by higher Lp(a)
      concentrations in comparison to controls. Treatment with octreotide (100 microg
      t.i.d. for 3 months) led to: an increase in HDL cholesterol (median: + 22%), a
      decrease in LDL cholesterol (-14%) and a decrease of the Lp(a) levels (all
      phenotypes) (-28%). The expected decreases of IGF-I levels (median: -48%) and 7-h
      AUC of GH (-50%), insulin (-40%) and glucagon (-20%) were observed. Only Lp(a)
      modifications showed a correlation with GH modifications. The study of LDL
      physical properties showed that acromegalic patients had smaller and/or more
      dense LDL particles, in comparison with normal controls (relative flotation rate,
      Rf: 0.40 +/- 0.03 versus 0.42 +/- 0.02 P < 0q05), an alteration that might
      contribute to the high vascular risk of acromegalic patients. However, the LDL
      subfraction distribution remained unmodified during octreotide therapy (Rf 0.39
      +/- 0.03). In conclusion, this study shows that in acromegalic patients
      octreotide treatment is indeed associated with an amelioration of some
      lipoprotein parameters, i.e. LDL, HDL, and Lp(a) concentrations. However, this
      treatment has no effect on the small and/or dense LDL particles present in these
      patients.

PMID- 10924735
TI  - Regulation of plasma low density lipoprotein levels in postmenopausal women.
AB  - To study the regulation of plasma low density lipoprotein (LDL) cholesterol in
      postmenopausal women (n = 79), fasting plasma lipids and lipoproteins, the
      fractional catabolic rate (FCR) and production rate for LDL apolipoprotein B (apo
      B), cholesterol absorption, apolipoprotein E phenotype and polymorphisms of the
      apo B and 7alpha-hydroxylase genes were determined. The level of LDL cholesterol
      was related to FCR (r= -0.757, P < 0.001) and the production (r= 0.531, P <
      0.001) of LDL apo B and body mass index (r = 0.265, P <0.05). In contrast,
      cholesterol absorption efficiency, apolipoprotein E phenotype, EcoRI and XbaI
      polymorphisms of the apo B gene and the polymorphism of 7alpha-hydroxylase gene
      were found to have no significance for the regulation of LDL cholesterol
      concentration in these postmenopausal women.

PMID- 10924736
TI  - The Pro12A1a substitution in the peroxisome proliferator activated receptor gamma
      2 is associated with an insulin-sensitive phenotype in families with familial
      combined hyperlipidemia and in nondiabetic elderly subjects with dyslipidemia.
AB  - Dyslipidemias and insulin resistance often present simultaneously, as in familial
      combined hyperlipidemia (FCHL), and therefore may have a common genetic
      background. In our previous study the Pro12A1a substitution of peroxisome
      proliferator receptor gamma 2 (PPARgamma2) associated with insulin sensitivity,
      low body mass index (BMI) and high-density lipoprotein (HDL) cholesterol levels.
      In this study, we investigated the role of this substitution in dyslipidemias.
      Therefore, 228 nondiabetic members of FCHL families and 866 nondiabetic elderly
      subjects with (n=217) and without dyslipidemia (n=649) were genotyped. The allele
      frequencies of the Pro12A1a substitution did not differ between elderly subjects
      with or without dyslipidemia or 27 probands with FCHL. However, this substitution
      was associated with low fasting insulin levels both in FCHL family members (P =
      0.036 adjusted for gender and age) and elderly subjects with dyslipidemia
      (P=0.050) but not in elderly subjects without dyslipidemia (P=0.080). In
      addition, the Ala12 allele of PPARgamma2 was associated with low BMI (P= 0.034)
      and low total triglycerides (P=0.027), and increased HDL-cholesterol (P < 0.001)
      in elderly subjects with dyslipidemia (n=299) but not among any other study
      groups. We conclude that the Ala12 isoform of PPARgamma2 ameliorates the insulin
      resistance and unfavorable lipid and lipoprotein profiles in FCHL and
      hyperlipidemic elderly subjects.

PMID- 10924738
TI  - Assessment of low-molecular-weight heparin trials in cardiology.
AB  - This review assesses the trial data for low-molecular-weight heparin (LMWH) use
      in cardiology. LMWHs have been shown to be more convenient to use compared with
      unfractionated heparin. The use of LMWHs in prevention and treatment of deep vein
      thrombosis is now established. Use of LMWHs in cardiology is gathering momentum.
      The most compelling published data are in unstable angina and non-Q-wave
      myocardial infarction (MI). LMWHs are at least as effective as unfractionated
      heparin in terms of the composite endpoint of death and MI. Conclusive benefits
      of LMWH use to prevent restenosis after stent insertion or percutaneous
      transluminal coronary angioplasty have not been established. The data in MI and
      atrial fibrillation are still preliminary, but encouraging.

PMID- 10924737
TI  - Intima-media thickness after pravastatin stabilizes also in patients with
      moderate to no reduction in LDL-cholesterol levels: the carotid atherosclerosis
      Italian ultrasound study.
AB  - The Carotid Atherosclerosis Italian Ultrasound study (CAIUS), a multicenter,
      double-blind clinical trial, performed in 305 asymptomatic, moderately
      hypercholesterolemic patients, clearly demonstrated beneficial effects of
      pravastatin on the carotid intima-media thickness (IMT) progression. The database
      of the CAIUS study was examined in order to investigate the presence of a
      relationship, if any, between the activity of pravastatin on IMT progression rate
      and its hypocholesterolemic effect. Quantitative B-mode ultrasound imaging was
      used to quantify the individual mean maximum IMT progression rate in 3 years. In
      the overall group of patients (placebo and pravastatin) covariance analysis
      showed that while the variable 'treatment' (0 = placebo, 1 = pravastatin) was
      significantly related to the reduction of IMT progression (F= 6.6, P = 0.01), the
      IMT progression did not correlate with the extent of LDL-C lowering (F= 0.00, P =
      0.98). To further investigate this issue. the pravastatin treated group was
      stratified into quartiles of LDL-C reduction. In contrast to what was observed in
      the placebo group, in which a positive mean IMT progression rate was observed,
      independent of the extent of LDL-C reduction, no IMT progressionwas observed in
      any subgroup treated with pravastatin. No significant difference was found among
      quartiles and no trend could be identified. In conclusion, the effect of
      pravastatin treatment on carotid IMT progression rate is beneficial; however the
      CAIUS study demonstrated that lowering LDL-C by itself, does not explain the
      variability of beneficial changes in IMT.

PMID- 10924739
TI  - The N-methyl-D-aspartate receptor, synaptic plasticity, and depressive disorder.
      A critical review.
AB  - The roles of the N-methyl-D-aspartate (NMDA) receptor and NMDA receptor-mediated
      synaptic plasticity are reviewed in the context of depressive disorder and its
      treatment. The mode of action of antidepressant treatment is poorly understood.
      Animal studies have suggested that many antidepressant drugs show activity at the
      NMDA receptor and that NMDA antagonists have antidepressant profiles in
      preclinical models of depression. A post-mortem study in humans has suggested
      that certain binding characteristics of the NMDA receptor may be down-regulated
      in the brains of suicide victims. "Depressogenic" stressors in animals and
      chronic administration of antidepressant agents perturb NMDA-dependent synaptic
      plasticity in the hippocampus.

PMID- 10924741
TI  - Molecular mechanism of angiogenesis transcription factors and their therapeutic
      relevance.
AB  - Controlling angiogenesis, either positively or negatively, is considered to be
      useful for the treatment of various diseases. Angiogenesis primarily depends on
      the phenotypic changes of vascular endothelial cells (ECs). Various genes are
      expressed in ECs during angiogenesis, and thus, understanding of the
      transcriptional control of these genes in ECs is very important. This review
      focuses on transcription factors that may play important roles in angiogenesis.

PMID- 10924740
TI  - The structure and mechanism of bacterial type I signal peptidases. A novel
      antibiotic target.
AB  - Type I signal peptidases are essential membrane-bound serine proteases that
      function to cleave the amino-terminal signal peptide extension from proteins that
      are translocated across biological membranes. The bacterial signal peptidases are
      unique serine proteases that utilize a Ser/Lys catalytic dyad mechanism in place
      of the classical Ser/His/Asp catalytic triad mechanism. They represent a
      potential novel antibiotic target at the bacterial membrane surface. This review
      will discuss the bacterial signal peptidases that have been characterized to
      date, as well as putative signal peptidase sequences that have been recognized
      via bacterial genome sequencing. We review the investigations into the mechanism
      of Escherichia coli and Bacillus subtilis signal peptidase, and discuss the
      results in light of the recent crystal structure of the E. coli signal peptidase
      in complex with a beta-lactam-type inhibitor. The proposed conserved structural
      features of Type I signal peptidases give additional insight into the mechanism
      of this unique enzyme.

PMID- 10924742
TI  - Selective activation of E-type prostanoid(3)-receptors reduces myocardial infarct
      size. A novel insight into the cardioprotective effects of prostaglandins.
AB  - Prostaglandins (PGs) and other eicosanoids are members of a large family of lipid
      mediators (autacoids). In 1978, Lefer and colleagues (Science 200, 52-55 [1978])
      reported that prostacyclin reduces the myocardial tissue injury caused by
      coronary artery occlusion and reperfusion in the cat. Since this discovery, more
      than 50 papers have reported on the cardioprotective effects of vasodilator PGs,
      including prostacyclin. The cardioprotective effects of PGs are due in part to
      (1) a reduction in afterload, (2) an increase in coronary blood flow, (3) the
      inhibition of platelet function, and (4) the inhibition of the activation and
      extravasation of polymorphonuclear granulocytes. All of these effects are
      secondary to the activation of EP (E-type prostanoid)(2)-receptors, which
      activate G(s)-protein and, hence, adenylate cyclase. In addition, the protection
      of organs such as the heart by PGs has been attributed to a cytoprotective effect
      of these agents, the mechanism of which is largely unknown. We recently have
      discovered that certain E-type PGs, which do not activate EP(2)-receptors, also
      reduce myocardial infarct size, without causing a fall in blood pressure (EP(2)
      receptor-mediated effects). Having provided a brief introduction into the role of
      eicosanoids in ischaemia-reperfusion injury of the heart, this review focuses on
      the recent discovery that selective agonists of EP(3)-receptors reduce myocardial
      infarct size, without causing haemodynamic side effects. The mechanisms of the
      cardioprotective effects of these agents are discussed, as are the therapeutic
      implications.

PMID- 10924743
TI  - Guest editorial

PMID- 10924744
TI  - Cytokine network at the feto-maternal interface.
AB  - There is much evidence that cytokines play a very important role in the
      maintenance of pregnancy by modulating immune and endocrine systems. Placental
      tissue produces cytokines and hormones that are essential to the regulation of
      the feto-maternal unit. Decidual lymphocytes express cell surface markers for
      activation, such as CD69 and HLA-DR, and these cells secrete many cytokines.
      Recent studies suggested that in pregnant women, cytokines produced by Th2 cells
      predominate over those produced by Th1 cells, resulting in the maintenance of
      pregnancy. This review article focuses on the unique cytokine network at the feto
      maternal interface in humans. Recently, we demonstrated that Th2 cells were
      dominant within the decidua in early pregnancy in humans. The Th2-derived
      cytokines, IL-4 and IL-6, induce the release of hCG from trophoblasts, and the
      hCG stimulate progesterone production from corpus luteum in pregnancy.
      Progesterone stimulates the secretion of Th2 and reduces the secretion of Th1
      cytokines. Thus, Th2 type cytokines appear to contribute to the maintenance of
      pregnancy by controlling the immune and endocrine systems and promoting the
      function of the trophoblasts at the implantation site.

PMID- 10924745
TI  - Cytokine regulation of apoptotic susceptibility in a human endometrial epithelial
      cell line.
AB  - The effects of four endometrial cytokines, transforming growth factor beta1 (TGF
      beta1), interleukin-1beta (IL-1beta), epidermal growth factor (EGF), and
      hepatocyte growth factor (HGF), on Fas-mediated apoptosis in the human
      endometrial epithelial cell line, HHUA, were investigated. Although the cell
      growth of HHUA was not directly affected by TGF-beta1, IL-1beta, or EGF,
      pretreatment of HHUA with TGF-beta1, IL-1beta, or EGF enhanced Fas-mediated
      growth suppression and Fas-mediated DNA fragmentation in the cells. Flow
      cytometric analyses demonstrated that TGF-beta1, IL-1beta, and EGF did not induce
      Fas expression on the cell surface. These results suggest that TGF-beta1, IL
      1beta, and EGF enhances apoptotic susceptibility of the cells. However, HGF
      inhibited Fas-mediated growth suppression and DNA fragmentation in the cells
      without any increase in Fas antigen expression on the cells. This finding
      suggests that HGF suppresses apoptotic susceptibility of the cells. From these
      results, we conclude that the endometrial cytokines may play a role in reshaping
      the endometrium after menstruation or in regulating apoptotic susceptibility in
      endometrial epithelium in the mid- to late-secretory period.

PMID- 10924746
TI  - Murine fetal resorption and experimental pre-eclampsia are induced by both
      excessive Th1 and Th2 activation.
AB  - It has been proposed that immune responses in mammalian normal pregnancy are Th2
      like, thereby protecting the fetus and placenta from being rejected.
      Administration of exogenous Th1 cytokines into pregnant mice is reported to
      induce feto-placental resorption. However, the effects of exogenous Th2 cytokines
      and Th2 directed responses in pregnant animals have not been well studied. In
      this study, we examined IL-4 and IL-12, which play decisive roles in the
      development of Th2 and Th1 responses, respectively, in the induction of fetal
      resorption and development of experimental pre-eclampsia. Transfer of either IL-4
      and/or IL-12 stimulated splenocytes from BALB/C virgin female mice into BALB/C
      pregnant mice mated with either C57BL/6 or BALB/C male mice resulted in fetal
      resorption and glomerular nephritis associated with hypertension and proteinuria.
      In mice treated with IL-12 stimulated splenocytes, fatty liver degeneration
      associated with bile retention was observed. These results indicate that both
      excessive Th1 and Th2 activation contribute to the development of fetal
      resorption and pre-eclampsia, but that Th1 is critical to the development of
      liver degeneration.

PMID- 10924747
TI  - Molecular and immunological approaches to mammalian fertilization.
AB  - By means of hybridoma technology, we obtained six hydriboma cell lines producing
      monoclonal antibody (mAb) to porcine zona pellucid (ZP), two of which recognizes
      the steric structure of common antigens between porcine ZP and humans.
      Furthermore, we have analyzed all or partial structures of N- and O-linked sugar
      chains of ZP glycprotein from porcine or murine oocytes. Then, we have clarified
      that beta-galactose and Le(X) residues on ZP played the binding roles to sperm
      cells in porcine and murine fertilization. We have also succeeded Sp38 cDNA
      cloning from cDNA library of porcine testis. We found that Sp38 protein bind to
      porcine ZP2 and expressed in murine and human sperm cells. Corresponding to the
      presence of major histocompatibility complex (MHC) class II on murine sperm, CD4
      on the murine egg plasma membrane was clearly shown by indirect IIF and
      immunoprecipitation test. Furthermore, the transcriptional expression of
      CD4/p56(lck) in eggs was confirmed by RT-PCR method. In addition, the p56(lck)
      associated with CD4 underneath the plasma membrane of eggs was autophosphorylated
      after cross-linking of CD4 with anti CD4 mAb. The binding between eggs or Sf9-CD4
      cells labeled with anti-CD4 mAb and sperm cells labeled with anti-monomorphic
      region of class II mAb was completely blocked. Considering these findings
      together with the fact that an interspecies' heterogeneity is present in CD4
      amino acid sequence at the interactive site with class II, we elucidated that one
      of species' specific intercellular adhesions between two gametes at the fusion
      step in fertilization is definitely mediated by class II located on the posterior
      region of sperm head and CD4/p56(lck) complex on the plasma membrane of egg.

PMID- 10924748
TI  - Analysis of B cell epitopes of a glycoprotein porcine zona pellucida (pZP1).
AB  - The zona pellucida (ZP) of mammalian oocytes forms an extracellular matrix
      composed of three major glycoproteins and plays an important role in sperm-zona
      interactions. As ZP had a strong organ-specific but species-cross-reactive
      antigenicity and passive or active immunization with ZP antigens could impair
      fertilization, the possibility of developing a immunocontraceptive vaccine has
      been extensively studied. Studies on active immunization with porcine ZP (pZP)
      that contain B cell epitopes and T cell epitopes demonstrated that a temporary
      infertility could be induced along with the elevation of antibody titers, but it
      was always associated with ovarian failure. This could be due to the oophoritis
      by activation of pathogenic T cell immunity. It is the general consideration that
      any adverse effects by vaccination should be avoided for an immunocontraception.
      From this point of view, the analysis of B cell epitopes of pZP protein would be
      helpful for construction of a safe immunocontraceptive vaccine with zona
      antigens. We determined the amino acid sequence of the B epitope in the pZP1
      protein by using a monoclonal antibody (MAb-5H4) that possesses a fertilization
      blocking ability. In addition, antiserum raised to the epitope sequence was
      revealed to block in vitro fertilization of homologous animal species.

PMID- 10924749
TI  - Plasma contact system, kallikrein-kinin system and antiphospholipid-protein
      antibodies in thrombosis and pregnancy.
AB  - Coagulation factor XII, prekallikrein and high molecular weight kininogen are
      known as plasma contact proteins in the intrinsic pathway of blood coagulation.
      Deficiencies of these proteins are not associated with clinical bleeding despite
      marked prolongation of in vitro surface-activated coagulation time.
      Paradoxically, studies suggest that these proteins have anticoagulant and
      profibrinolytic activities. In fact, association between deficiencies of these
      proteins as well as recurrent thrombosis has been reported. Also deficiencies of
      these proteins and antiphospholipid antibodies are frequent haemostasis-related
      abnormalities found in unexplained recurrent aborters. Recently, evidence has
      accumulated for the presence of the kallikrein-kinin system or plasma contact
      system in the fetoplacental unit. This suggests that the plasma contact system
      may also have an important role in pregnancy. Several studies have reported the
      presence of autoantibodies to the contact proteins in patients with SLE,
      thrombosis and recurrent pregnancy loss. These autoantibodies are often in
      association with antiphospholipid antibodies and lupus anticoagulants. Contact
      proteins may be added to the list of proteins to which autoantibodies are
      produced in patients assigned to antiphospholipid antibody syndrome.

PMID- 10924750
TI  - Cytokine production in chorioamnionitis.
AB  - Lymphohematopoietic cytokines play a significant role in many biological
      mechanisms including a number of reproductive processes such as ovulation,
      implantation, placentation, cervical dilation and parturition. Recent experiments
      have suggested that cytokines play a crucial role in the mechanisms of preterm
      labor and delivery, which are the leading causes of perinatal morbidity and
      mortality. Growing evidence suggests that infection is deeply concerned in the
      pathogenesis of preterm labor and delivery. Chorioamnionitis, a subset of
      intrauterine infection, has been identified in 20-33% of women with preterm
      delivery, and the inflammatory and related cytokines, interleukin-1 (IL-1), tumor
      necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8),
      showed substantial increases in the amniotic fluid at women with intrauterine
      infection. Although the precise mechanism for chorioamnionitis-driven preterm
      labor mediated via cytokines is still unknown, both IL-1 and TNF-alpha along with
      IL-6 enhance prostaglandin production by human amnion cells, chorionic cells and
      decidual cells. Analysis of the regulatory sequences in the 5' upstream regions
      of receptor gene for human oxytocin, a potent uterotonic agent, suggests a close
      relationship between preterm labor and inflammatory cytokines through induction
      at the oxytocin receptor. Prompt identification of the patients with intra
      amniotic infection may be useful in clinical practice. At present, the
      measurement of IL-8 in maternal serum or the measurement of IL-6 in cervical
      secretion may be helpful as a non-invasive screening for chorioamnionitis.

PMID- 10924751
TI  - HTLV-I transmission from mother to child.
AB  - Human T-lymphotropic virus type I (HTLV-I), a causative agent of adult T-cell
      leukemia, (ATL) is transmitted from mother to child. ATL cells originate from the
      CD4 subset of peripheral T cells. The main route of mother-to-child transmission
      is postnatal breast-feeding. Refraining from breast-feeding or limiting the
      duration of breast-feeding can reduce the risk of mother-to-child transmission.
      Other than postnatal breast-feeding, there seem to be two routes of HTLV-I
      transmission from mother to child. One is intrauterine transmission, and the
      other is via saliva. Intrauterine transmission is rare, although proviral DNA is
      detected in cord blood samples. HTLV-I proviruses in the cord blood may be
      defective. HTLV-I proviral DNA and antibodies against HTLV-I are also detected in
      saliva. However, no report has been published so far which showed direct evidence
      of HTLV-I transmission via saliva. The placenta can be infected by HTLV-I, but
      infection does not reach the fetus, possibly apoptosis of placental villous cells
      because it is induced by HTLV-I infection.

PMID- 10924752
TI  - The size difference between leishmania major friedlin chromosome one homologues
      is localized to sub-telomeric repeats at one chromosomal end.
AB  - Leishmania species are members of the evolutionarily ancient protozoan order
      Kinetoplastidae and are important human pathogens. The Leishmania genome is
      relatively small (approximately 34 Mbp) and is distributed among 36 chromosome
      pairs, ranging in size from 0.3 to 2.5 Mbp. The smallest chromosome of Leishmania
      major Friedlin, chrl, consists of three homologues which differ in size by
      approximately 29 kb. Previous sequence and Southern analyses of all three
      homologues reveal a conserved chromosomal core, consisting of coding and adjacent
      'non-informational' sequence. Here we show the size difference between homologues
      is largely restricted to variation in both the number and content of several sub
      telomeric repetitive elements localized on one chromosomal end. These repetitive
      elements also occur on other chromosomes, but some are more dispersed in the
      Leishmania genome than others.

PMID- 10924753
TI  - Effects of interruption of apicoplast function on malaria infection, development,
      and transmission.
AB  - A chloroplast-like organelle is present in many species of the Apicomplexa
      phylum. We have previously demonstrated that the plastid organelle of Plasmodium
      faciparum is essential to the survival of the blood-stage malaria parasite in
      culture. One known function of the plastid organelle in another Apicomplexan,
      Toxoplasma gondii, involves the formation of the parasitophorous vacuole. The
      effects of interruption of plastid function on sporozoites and sexual-stage
      parasites have not been investigated. In our previous studies of the effects of
      thiostrepton, a polypeptide antibiotic from streptococcus spp., on erythrocytic
      schizongony of the human malaria P. falciparium, we found that this antibiotic
      appears to interact with the guanosine triphosphatase (GTPase) binding domain of
      the organellar large subunit ribosomal RNA, as it does in bacteria. We
      investigate here the effects of this drug on life-cycle stages of the malaria
      parasite in vivo. Preincubation of mature infective sporozoites with thiostrepton
      has no observable effect on their infectivity. Sporozoite infection both by
      mosquito bite and sporozoite injection was prevented by pretreatment of mice with
      thiostrepton. Thiostrepton eliminates infection with erythrocytic forms of
      Plasmodium berghei in mice. Clearance of infected red blood cells follows the
      delayed kinetics associated with drugs that interact with the apicoplast.
      Thiostrepton treatment of infected mice reduces transmission of parasites by more
      than ten-fold, indicating that the plastid has a role in sexual development of
      the parasite. These results indicate that the plastid function is accessible to
      drug action in vivo and important to the development of both sexual and asexual
      forms of the parasite.

PMID- 10924754
TI  - Role of alcohol dehydrogenase E (ADHE) in the energy metabolism of Giardia
      lamblia.
AB  - Two hammerhead ribozymes flanked by Giardia lamblia alcohol dehydrogenase E
      (ADHE) antisense RNA fragments, ARzS and ARzL, were designed, synthesized and
      found capable of cleaving an ADHE mRNA fragment at the anticipated position in
      vitro. The ribozymes were then electroporated into Giardia trophozoites and
      expressed via the giardiavirus-mediated RNA expression system. Expression of the
      ribozyme with two short antisense arms, ARzS, was stabilized under puromycin
      selection and demonstrated a 33% reduction in ADHE mRNA and 25% decrease in NAD+
      dependent ADH activity in the transfectants. Expression of ARzL, the ribozyme
      with two long antisense arms, cannot be enriched under puromycin without killing
      the transfected cells, probably due to excessive depletion of ADHE. Without the
      drug selection, however, transient expression of ARzL 20-40 h after
      electroporation resulted in an 83.7% loss of ADHE mRNA and an 84.5% reduction in
      ADH activity in the transfected cells. When the ribozyme moiety was removed from
      ARzL, the latter retained some of its in vivo activity of lowering ADHE mRNA and
      ADH activity, suggesting that inhibition of ADHE gene expression in Giardia can
      be accomplished by the antisense RNA alone, albeit less efficiently. The ADHE
      deficient transfectant demonstrated relatively poorer anaerobic growth but grew
      more vigorously than the wild type under aerobic conditions, suggesting that the
      role of ADHE in providing NAD+ through anaerobic reduction of acetyl-CoA to
      ethanol could be replaced by a yet unidentified aerobic enzyme(s) in Giardia. The
      close association consistently observed between the levels of ADHE mRNA and ADH
      activity in transfected Giardia cells suggests that ADHE could be the only
      functional alcohol dehydrogenase in Giaradia. One other Giardia gene encoding a
      putative Class III ADH, GIADH3, was identified and cloned, but no Class III ADH
      activity could be detected in Giardia by the conventional enzyme assays. This
      gene is thus probably unexpressed in Giardia trophozoite.

PMID- 10924755
TI  - Putrescine and spermidine transport in Leishmania.
AB  - The transport of putrescine and spermidine into Leishmnania donovani
      promastigotes and Leishmania mexicana promastigotes and amastigotes has been
      characterised. Polyamine transport was shown to be saturable and temperature
      sensitive for both developmental stages of Leishmania. Transport was pH-dependent
      with pH optima of 7.4 and 5.5 for promastigotes and amastigotes, respectively.
      The uptake process was independent of extracellular Na+, but inhibited by
      protonophores and H+-ATPase inhibitors. Kinetic analyses of polyamine transport
      showed that Km and Vmax differed between promastigotes of the two species and
      between promastigotes and amastigotes of L. mexicana. Inhibition data suggest
      that putrescine and spermidine use different transporters. The aromatic diamidine
      pentamidine, the drug of choice for treatment of antimonial-resistant cases of
      leishmaniasis, inhibited both putrescine and spermidine transport non
      competitively.

PMID- 10924756
TI  - Altered expression of cruzipain and a cathepsin B-like target in a Trypanosoma
      cruzi cell line displaying resistance to synthetic inhibitors of cysteine
      proteinases.
AB  - The therapeutic potential of synthetic inhibitors to the major cysteine
      proteinase from Trypanosoma cruzi (cruzain or cruzipain) was recently
      demonstrated in animal models of Chagas' disease. A possible limitation of this
      strategy would be the emergence of parasite populations developing resistance to
      cysteine-proteinase inhibitors. Here, we describe the properties of a
      phenotypically stable T. cruzi cell line (R-Dm28) that displays increased
      resistance to Z-(SBz)Cys-Phe-CHN2, an irreversible cysteine-proteinase inhibitor
      which preferentially inactivates cathepsin L-like enzymes. Isolated from axenic
      cultures of the parental cells (IC50 1.5 microM), R-Dm28 epimastigotes exhibited
      13-fold (IC50) 20 microM) higher resistance to this inhibitor and did not display
      cross-resistance to unrelated trypanocidal drugs, such as benznidazol and
      nifurtimox. Western blotting (with mAb), affinity labeling (with biotin-LVG-CHN2)
      and FACS analysis of R-Dm28 log-phase epimastigotes revealed that the cruzipain
      target was expressed at lower levels, as compared with Dm28c. Interestingly, this
      deficit was paralleled by increased expression of an unrelated Mr 30 000 cysteine
      proteinase whose activity was somewhat refractory to inhibition by Z-(SBz)Cys-Phe
      CHN,. N-terminal sequencing of the affinity-purified biotin-LVG-proteinase
      complex allowed its identification as a cathepsin B-like enzyme. Increased
      antigenic deposits of this proteinase were found in the grossly enlarged and
      electron dense reservosomes from R-Dm28 epimastigotes. Our data suggest that R
      Dm28 resistance to toxic effects induced by the synthetic inhibitor may result
      from decreased availability of the most sensitive cysteine-proteinase target,
      cruzipain. The deficit in metabolic functions otherwise mediated by this
      cathepsin L-like proteinase is likely compensated by increased
      expression/accumulation of a cathepsin B-like target.

PMID- 10924757
TI  - Glycosylation and palmitoylation are common modifications of giardia variant
      surface proteins.

PMID- 10924758
TI  - Phylogenetic analysis with newly characterized Babesia bovis hsp70 and hsp90
      provides strong support for paraphyly within the piroplasms.

PMID- 10924759
TI  - Expression of the AM gene locus in infective stages of Leishmania.

PMID- 10924760
TI  - Screening for Theileria parva secretory gene products by functional analysis in
      Saccharomyces cerevisiae.

PMID- 10924762
TI  - Age-related decline in central serotonin transporter availability with
      [(123)I]beta-CIT SPECT.
AB  - Postmortem studies have provided limited and conflicting data regarding aging
      effects on the central serotonin transporter (SERT). The present study
      investigated the effect of age on SERT availability in the human brainstem and
      diencephalon with single photon emission computed tomography (SPECT) using the
      ligand [(123)I]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([(123)I]beta
      CIT). Healthy control subjects (n = 126) who ranged in age from 18 to 88 were
      injected with 6.0 +/- 0.8 (mean +/- SD) mCi [(123)I]beta-CIT and imaged 23.1 +/-
      1.9 h later under equilibrium conditions. A ratio of specific to nondisplaceable
      brain uptake (i.e. , V(3)" = [brainstem-diencephalon -occipital]/occipital), a
      measure proportional to the binding potential (B(max)/K(D)), was derived. SERT
      availability (V(3)") showed a significant inverse correlation with age (r = 
      0.40, P < 0.0001). Linear regression analysis revealed that V(3)" declined by
      29.5% over the age range 18 to 88, or approximately 4.2% per decade. These
      results demonstrate reductions in the availability of central SERT binding sites
      with age in living human subjects.

PMID- 10924763
TI  - Casein kinase 1 delta is associated with pathological accumulation of tau in
      several neurodegenerative diseases.
AB  - The distribution of casein kinase 1 delta (Cki delta) was studied by
      immunohistochemistry and correlated with other pathological hallmarks in
      Alzheimer's disease (AD), Down syndrome (DS), progressive supranuclear palsy
      (PSP), parkinsonism dementia complex of Guam (PDC), Pick's disease (PiD), pallido
      ponto-nigral degeneration (PPND), Parkinson's disease (PD), dementia with Lewy
      bodies (DLB), amyotrophic lateral sclerosis (ALS), and elderly controls. Cki
      delta was found to be associated generally with granulovacuolar bodies and tau
      containing neurofibrillary tangles in AD, DS, PSP, PDC, PPND, and controls, and
      Pick bodies and ballooned neurons in PiD. It was not associated with tau
      containing inclusions in astroglia and oligodendroglia in PPND, PSP, and PDC. It
      was also not associated with tau-negative Lewy bodies in PD and DLB, Hirano
      bodies in PDC, Marinesco bodies in PD, AD, and controls and "skein"-like
      inclusions in anterior motor neurons in ALS. The colocalization of the kinase Cki
      delta and its apparent substrate tau suggests a function for Cki delta in the
      abnormal processing of tau.

PMID- 10924764
TI  - Morphological and biochemical assessment of DNA damage and apoptosis in Down
      syndrome and Alzheimer disease, and effect of postmortem tissue archival on
      TUNEL.
AB  - We have previously shown that Alzheimer disease (AD) brain exhibits terminal
      deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) for DNA damage and
      morphological evidence for apoptosis. Down syndrome (DS) is a neurodegenerative
      disorder that exhibits significant neuropathological parallels with AD. In
      accordance with these parallels and the need to clarify the mechanism of cell
      death in DS and AD, we investigated two principal issues in the present study.
      First, we investigated the hypothesis that TUNEL labeling for DNA damage and
      morphological evidence for apoptosis is also present in the DS brain. All DS
      cases employed had a neuropathological diagnosis of AD. Analysis of these cases
      showed that DS brain exhibits a significant increase in the number of TUNEL
      labeled nuclei relative to controls matched for age, Postmortem Delay, and
      Archival Length, and that a subset of TUNEL-positive nuclei exhibits apoptotic
      morphologies. We also report that Archival Length in 10% formalin can
      significantly affect TUNEL labeling in postmortem human brain, and therefore,
      that Archival Length must be controlled for as a variable in this type of study.
      Second, we investigated whether biochemical evidence for the mechanism of cell
      death in DS and AD could be detected. To address this question we employed pulsed
      field gel electrophoresis (PFGE) as a sensitive method to evaluate DNA integrity.
      Although apoptotic oligonucleosomal laddering has not previously been observed in
      AD, PFGE of DNA from control, DS and AD brain in the present study revealed
      evidence of high molecular weight DNA fragmentation indicative of apoptosis. This
      represents biochemical support for an apoptotic mechanism of cell death in DS and
      AD.

PMID- 10924765
TI  - NAD(P)H:quinone oxidoreductase activity is increased in hippocampal pyramidal
      neurons of patients with Aalzheimer's disease.
AB  - NAD(P)H:quinone oxidoreductase (QR) catalyzes the two-electron reduction of
      quinones, preventing their participation in redox cycling and subsequent
      generation of reactive oxygen species. Pretreatment of neuroblastoma cells with
      compounds, such as tert-butylhydroquinone and dimethyl fumarate, that increase QR
      expression protect cells from oxidative stress-induced cell death by glutamate,
      H(2)O(2,) and dopamine. The potential neuroprotective role of QR as well as the
      evidence for oxidative stress-induced neuronal cell death in Alzheimer's disease
      (AD) led us to examine the expression pattern of QR from AD and control patients.
      Histochemical staining of hippocampal sections from AD patients revealed QR
      activity in pyramidal neurons. The presence of QR protein in these neurons also
      was confirmed by immunoreactivity. In control patients, hippocampal pyramidal
      neurons were negative for both QR enzymatic activity and QR immunoreactivity. In
      addition, the QR positive neurons of AD patients were selectively located in
      areas where neuronal populations exhibited tau immunostaining. Our data
      demonstrate that QR is up-regulated in hippocampal pyramidal neurons of AD
      patients. We hypothesize that this is part of a neuroprotective system up
      regulated in response to the AD process. Understanding this system may lead to
      further insights into the pathogenesis and potential new avenues of treatment for
      AD.

PMID- 10924766
TI  - Quantitative electroencephalography in mild cognitive impairment: longitudinal
      changes and possible prediction of Alzheimer's disease.
AB  - The present study evaluated the clinical course of patients with mild cognitive
      impairment (MCI), the pattern of electroencephalography (EEG) changes following
      cognitive deterioration, as well as the potential of neurophysiological measures
      in predicting dementia. Twenty-seven subjects with MCI were followed for a mean
      follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to
      clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S
      MCI). The two MCI subgroups did not differ in baseline EEG measures between each
      other and the healthy controls (n = 16), but had significantly lower theta
      relative power at left temporal, temporo-occipital, centro-parietal, and right
      temporo-occipital derivation when compared to the reference AD group (n = 15).
      The P MCI baseline alpha band temporo-parietal coherence, alpha relative power
      values at left temporal and temporo-occipital derivations, theta relative power
      values at frontal derivations, and the mean frequency at centro-parietal and
      temporo-occipital derivations overlapped with those for AD and control groups.
      After the follow-up, the P MCI patients had significantly higher theta relative
      power and lower beta relative power and mean frequency at the temporal and
      temporo-occipital derivations. A logistic regression model of baseline EEG values
      adjusted for baseline Mini-Mental Test Examination showed that the important
      predictors were alpha and theta relative power and mean frequency from left
      temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects
      correctly.

PMID- 10924767
TI  - Spatial learning in transgenic mice expressing human presenilin 1 (PS1)
      transgenes.
AB  - Dominant mutations in the Presenilin 1 gene are linked to an aggressive, early
      onset form of familial Alzheimer's Disease (FAD). Spatial memory of transgenic
      (Tg) mice expressing either mutant (lines Tg(M146L)1, Tg(M146L)76, Tg(L286V)198)
      or wild type (line Tg(PS1wt)195) human PS1 transgenes was investigated in the
      Morris water maze (WM) test at 6 and 9 months of age. The results showed that the
      mutated Tg mice had increased swim speed when compared to non-Tg littermates or
      Tg PS1 wild type mice. The swim speed difference did not, however, significantly
      affect the spatial learning in the WM test and all groups showed comparable
      search paths during training and similar spatial bias during probe trials. When
      re-tested at 9 months, all mice showed significantly improved learning
      acquisition of spatial information. The lack of progressive spatial learning
      impairment in mice expressing the mutated human PS1 transgene in the WM does not
      preclude impairments in other cognitive tasks but suggests that full phenotypic
      expression of mutant PS1 alleles may require co-expression of human versions of
      other AD-associated genes.

PMID- 10924768
TI  - Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's
      disease.
AB  - Bilirubin, an efficient antioxidant, is the end product of the heme cleavage
      pathway, which is catalyzed by heme oxygenase (HO) and biliverdin reductase.
      Although an inducible form of HO is overexpressed in the Alzheimer's disease (AD)
      brain, it has not been determined whether bilirubin metabolism is actually
      activated or not. In this study, we measured CSF-bilirubins and their derivatives
      using an enzyme-linked immunosorbent assay with two kinds of anti-bilirubin
      monoclonal antibodies, designated 24G7 and 5M2. In AD patients, the levels of CSF
      bilirubin derivatives increased significantly compared with those of controls.
      This increase was not due to the increased permeability of the blood-brain
      barrier, because the levels of unconjugated bilirubin were not different between
      AD and controls. These data may reflect the increase of degraded bilirubin
      metabolites in the AD brain derived from the scavenging reaction against chronic
      oxidative stress.

PMID- 10924769
TI  - Apolipoprotein E polymorphism in Pick's disease and in Huntington's disease.
AB  - The polymorphism of apolipoprotein E (apoE) has been recognized as a genetic risk
      factor in different neurodegenerative disorders, with or without tau protein-
      related neuropathology, but few published epidemiological data are available as
      concerns the association of different apoE alleles with two relatively rare forms
      of dementia, Pick's disease (PiD) and Huntington's disease (HD). In this study
      the frequency of the apoE4 allele was examined in 36 persons with
      histopathologically proven PiD and compared with that of the apoE genotype in 28
      HD probands and 79 aged healthy controls. The E4 allele was overrepresented
      selectively in PiD (42%) as compared with the control population (7%). No such
      association was found for HD probands (9%). This finding lends further support to
      the hypothesis that the E4 genotype is not an Alzheimer's disease specific
      susceptibility factor, and that it could be present in diverse dementing
      disorders with tau protein related neuropathology, such as PiD.

PMID- 10924771
TI  - Cogitations on a proteocentric lexicon.

PMID- 10924772
TI  - Will "cerebral proteopathy" be a useful construct for discovering one drug that
      shows efficacy against multiple neurodegenerative diseases?

PMID- 10924770
TI  - The cerebral proteopathies.

PMID- 10924773
TI  - Protein conformational diseases: the case for new semantic currency

PMID- 10924774
TI  - The relation between global and limbic brain volumes on MRI and cognitive
      performance in healthy individuals across the age range.
AB  - The present study investigated the range of age-related changes in brain
      morphology and the relation with performance on memory and other cognitive tests
      in a healthy population. A group of 61 subjects (21 to 81 years old, mean =
      55.7), free from cognitive and medical deficits, underwent MRI scanning and
      neuropsychological assessment encompassing memory and other cognitive tests.
      Volumetry of the hippocampus, parahippocampal gyrus, mamillary bodies, third
      ventricle, and total brain matter was performed. The results indicate that in
      healthy individuals increases in ventricular volume and volume decreases in total
      brain matter, hippocampus and parahippocampal gyrus, but not mamillary bodies,
      are clearly apparent with increasing age. However, no relation could be
      established between the brain volumes and test performance when controlling for
      the effects of age. To conclude, variations in total and limbic brain volumes do
      not seem predictive for cognitive performance independent of age.

PMID- 10924775
TI  - Age-related differences in visual perception: a PET study.
AB  - To assess age-related differences in cortical activation during form perception,
      two classes of visual textures were shown to young and older subjects undergoing
      positron emission tomography (PET). Subjects viewed even textures that were rich
      in rectangular blocks and extended contours and random textures that lacked these
      organized form elements. Within-group significant increases in regional cerebral
      blood flow (rCBF) during even stimulation relative to random stimulation in young
      subjects were seen in occipital, inferior and medial temporal regions, and
      cerebellum, and in older subjects, in posterior occipital and frontal regions.
      Group by texture type interactions revealed significantly smaller rCBF increases
      in older subjects relative to young in occipital and medial temporal regions.
      These results indicate that young subjects activate the occipitotemporal pathway
      during form perception, whereas older subjects activate occipital and frontal
      regions. The between-group differences suggest that age-related reorganization of
      cortical activation occur during early visual processes in humans.

PMID- 10924776
TI  - The role of mineralocorticoid receptors in the circadian activity of the human
      hypothalamus-pituitary-adrenal system: effect of age.
AB  - The purpose of this study was to test the role of the mineralocorticoid receptor
      (MR) in the circadian activity of the hypothalamus-pituitary-adrenal (HPA) system
      of elderly healthy subjects. Nine elderly subjects (age: 66.2 +/- 7.7 years) were
      treated for 8 days with both the MR antagonist spironolactone and a placebo in a
      randomized, single-blind cross-over order. After treatment, we studied the
      circadian profiles of ACTH, plasma cortisol and saliva cortisol. No significant
      change in ACTH concentrations emerged. However, there were significant increases
      in circadian minimal (52.4 +/- 26.7 versus 33.3 +/- 14.4 nmol/l), mean (166.2 +/-
      24.9 versus 133.0 +/- 18.3 nmol/l), and maximal cortisol concentrations (389.7 +/
      57.7 versus 335.4 +/- 45.0 nmol/l). Also, in the diurnal trough, we found an
      increase in saliva cortisol concentrations. Compared to young healthy controls,
      spironolactone treatment had stronger effects in the elderly. We therefore
      conclude that: 1) MR is involved in the human HPA system regulation; 2) the MR
      participates in the regulation of circadian nadir and peak activity of the HPA
      system; and 3) the HPA system in the elderly is more vulnerable to dysregulation
      at the level of the MR.

PMID- 10924777
TI  - Age-related decline in striatal volume in monkeys as measured by magnetic
      resonance imaging.
AB  - Age-related declines in striatal markers for the dopamine system have been
      demonstrated in several species. The current study investigated structural
      changes during aging in the rhesus monkey striatum. Male monkeys were studied
      using a volumetric spoiled gradient recall (SPGR) magnetic resonance imaging
      protocol. The caudate nucleus and putamen were segmented by manual tracing using
      landmarks made in the orthogonal planes. The whole brain volume (defined as
      volume of gray and white matter plus cerebrospinal fluid in ventricles and sulci)
      was measured using a semi-automated algorithm. There was no correlation between
      age and whole brain volume. There were age-related declines in normalized (i.e.
      brain region/whole brain volume) caudate nucleus and putamen volumes. Monkeys in
      the young group (n = 7, 39-45 months old) had larger volumes of both the caudate
      nucleus and putamen than animals in the middle-age (n = 5, 120-180 months) or old
      (n = 7, 291-360 months) groups. The current results provide normative data to
      assess potential interventions (e.g. caloric restriction) in the aging process.

PMID- 10924778
TI  - RNA editing (Q/R site) and flop/flip splicing of AMPA receptor transcripts in
      young and old brains.
AB  - The effects of aging on the efficiency of RNA processing of AMPA glutamate
      receptor (GluR) subunits GluR1, GluR2, and GluR 3 was examined for RNA editing at
      the Q/R site of GluR2 and for alternative splicing of the flip or flop exons for
      GluR1-3. RNA isolated from six young (3 months old) and old (22-23 months old)
      animals was reverse-transcribed for PCR and restriction endonuclease analyses to
      distinguish between edited forms of GluR2 and flip/flop isoforms of GluR1-3.
      Unedited transcripts of GluR2 at the Q/R site (which controls calcium
      permeability) were not detected (at the limit of detection of >/= 2.5%) from the
      corticies and hippocampi of young and old animals. Distribution of flop/flip
      isoforms in the cortex, hippocampus, hypothalamus, and striatum varied between
      GluR subunits and brain region, with GluR2 showing the greatest differences.
      However, no differences in alternative splicing of GluRs 1-3 were observed
      between young and old animals, suggesting that the fidelity of GluR transcript
      processing remains intact in the brains of aged animals.

PMID- 10924779
TI  - Excitatory amino acid receptors in the prefrontal cortex of aging mice.
AB  - The zones of the prefrontal cortex of Balb/c mice were tested for age-related
      changes of the ionotropic excitatory amino acid receptors density, together with
      zones of the dorsal cortex. Kainate, N-methyl-D-aspartate, and amino-3-hydroxy-5
      methyloxazole-4-propionate sites were measured by slice receptor binding
      techniques in cortical zones from animals at the age of 6, 12, 18, and 24 months.
      An increase of the N-methyl-D-aspartate sites was detected in the medial
      prefrontal zone of mid-aged animals and was followed by a decrease at old age; a
      decrease of the N-methyl-D-aspartate and kainate sites was found for the medial
      dorsal (cingulate) cortex at old age. The age-related changes of receptor
      densities in the different cortical areas seem unrelated in origin. The sites
      decrease in the cingulate cortex could affect the transfer of the prefrontal
      cortex activity toward limbic structures.

PMID- 10924780
TI  - Neutralization epitopes on the antigenic domain II of the Orientia tsutsugamushi
      56-kDa protein revealed by monoclonal antibodies.
AB  - Monoclonal antibodies (MoAbs) reactive with the authentic Orientia tsutsugamushi
      56-kDa protein were generated. MoAb FS10 and FS15 showed in vitro, as well as, in
      vivo neutralizing activity upon O. tsutsugamushi infection. Deletion mutants of
      the gene for 56-kDa protein of O. tsutsugamushi Boryong were expressed to map the
      binding region. FS10 and FS15 are bound to amino acids (aa) located in an
      antigenic domain II, at residues 140-160 and 187-214, respectively. Computer
      modeling indicated that aa 146-153 were important for antigenicity against FS10.
      A sequence for aa 142-150 was highly homologous between oriential strains. These
      results suggest that the antigenic determinant for neutralizing MoAbs is an
      epitope within aa 140-160. Furthermore, this region may be important for the
      adhesion/invasion or intracellular survival of O. tsutsugamushi within host
      cells.

PMID- 10924781
TI  - Dose range evaluation of a new inactivated hepatitis A vaccine administered as a
      single dose followed by a booster.
AB  - A total of 242 healthy adults were immunised with a first dose of an
      investigational inactivated hepatitis A vaccine. Three concentrations (3, 6 and
      12 EU [ELISA units]) of the experimental vaccine were used and compared to a
      licensed reference vaccine. The aim was to determine the antigenic concentration
      of the study vaccine inducing the highest seroconversion rate and anti-Hepatitis
      A virus (HAV) antibody response at 2 weeks after the primary immunisation. A
      booster dose was given at month 6. At 15 days after the primary immunisation the
      seroconversion rates in subjects vaccinated with the 6 and 12 EU vaccines were 78
      and 94%, respectively. At 30 and 180 days after the primary immunisation the
      percentages of seropositivity were 100% for both groups. The antibody response to
      the 12 EU study vaccine was similar to that to the reference vaccine. The
      percentages of seropositivity at 15 and 180 days after the primary immunisation
      were 94 vs 93%, and 100 vs 93% in the experimental and reference vaccine
      respectively. Thus, because it induces early and lasting seroconversion, the 12
      EU study vaccine seems to be the most effective as a high potency HAV vaccine.

PMID- 10924782
TI  - Can monovalent hepatitis A and B vaccines be replaced by a combined hepatitis A/B
      vaccine during the primary immunization course?
AB  - A combined hepatitis A/B vaccine (Twinrix Adult) has been licensed in Germany
      since 1997. We investigated possible differences in immunogenicity and safety
      when changing over from vaccinations with monovalent vaccines made by different
      manufacturers to vaccinations with the combined hepatitis A/B vaccine in an open,
      randomized, multicenter trial. We therefore compared four different schemes
      changing over from concomitant vaccinations with monovalent vaccines against
      hepatitis A and B (Havrix 1440+Engerix-B or Vaqta+Gen H-B-Vax) to combined
      vaccination against hepatitis A+B with three injections of the combined hepatitis
      A/B vaccine (0, 1, and 6 month schedule). Local and general symptoms were mostly
      mild in all five groups. With complete three-dose course using the combined
      vaccine or an early changeover from monovalent vaccines to the combined vaccine,
      higher overall anti-HBs seroprotection rates and geometric mean concentrations
      (GMCs) against hepatitis B could be achieved as early as after 2 months as
      compared to those groups switching later to the combined vaccine. This study
      demonstrated for the first time that switching from monovalent hepatitis A and B
      vaccinations to the combined hepatitis A and B vaccination has no negative
      influence on the tolerability and improves the immunogenicity.

PMID- 10924783
TI  - In vivo antigen loading and activation of dendritic cells via a liposomal peptide
      vaccine mediates protective antiviral and anti-tumour immunity.
AB  - Initiation of antiviral and anti-tumour T cell responses is probably achieved
      mainly by dendritic cells (DC) transporting antigen from the periphery into
      organised lymphoid tissues. To develop T cell vaccines it is, therefore,
      important to understand the accessibility of the antigen to DC in vivo and
      whether DC are activated by vaccination. Here we have evaluated the
      immunogenicity of a liposomal vaccine formulation with antigenic peptides derived
      from the glycoprotein of the lymphocytic choriomeningitis virus. Liposome
      encapsulated peptides were highly immunogenic when administered intradermally and
      elicited protective antiviral immunity. After intradermal injection, liposomes
      formed antigen depots which facilitated long-lasting in vivo antigen loading of
      dendritic cells almost exclusively in the local draining lymph nodes. The
      immunogenicity of the liposomal peptide vaccine was further enhanced by
      incorporation of immunostimulatory oligonucleotides leading to activation of DC.
      This optimised liposomal peptide vaccine elicited also anti-tumour immunity and
      induced CTL responses comparable to adoptively transferred, peptide-presenting
      DC. Thus, our data show that liposomal formulations of peptide vaccines are
      highly effective at direct in vivo antigen loading and activation of DC leading
      to protective antiviral and anti-tumour immune responses.

PMID- 10924784
TI  - The hidden costs of infant vaccination.
AB  - Combination vaccines to minimize injections required for infant vaccination, and
      new vaccines with improved safety profiles, will pose increasingly complex
      choices for vaccine purchasers in the future. How much of a premium to pay for
      such vaccines might be determined by taking into account (1) the psychological
      burden of multiple injections during a single clinic visit, and the costs of any
      additional visits to minimize these, and (2) the medical, work-loss, and
      incidental costs of common vaccine-associated symptoms. This cross-sectional
      survey included randomly-selected parents of 1-8-month-old infants who received
      vaccines in a Northern California health maintenance organization (HMO) in 1997.
      Interviewers called parents 14 days after the infant's vaccination to administer
      a 10-minute closed-ended interview in English or Spanish. Parents were asked
      about infant symptoms after vaccination, their preferences regarding multiple
      injections and their (theoretical) willingness to pay to reduce the number of
      injections their infant would receive, or to avoid the adverse symptoms
      experienced. Among 1769 eligible infants, interviews were completed with parents
      of 1657 (93%). The psychological cost of multiple injections was estimated by the
      willingness of parents to pay a median of $25 to reduce injections from 4 to 3,
      $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean
      costs of $42 in medical utilization and $192 in work-loss among the families who
      experienced those events (Ns=62 and 35, respectively). When averaged among all
      1657 study infants, vaccine-associated symptoms after the index vaccination visit
      resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct
      nonmedical costs, yielding total financial costs of $7.70. Parents of infants who
      had vaccine-associated symptoms said they would have paid a median of $50 to
      avoid these symptoms. Fever and fussiness were associated in logistic regression
      analysis with a two-fold increase in the odds of medical utilization, and fever
      with more than a three-fold increase in work loss. We conclude that multiple
      injections during a single clinic visit entail psychological costs. The
      psychological costs of vaccine-associated symptoms, as measured by willingness-to
      pay methods, are higher than those resulting from multiple injections. The
      financial costs of medical utilization and work-loss resulting from common
      vaccine-associated symptoms are non-negligible and should be incorporated in
      economic analyses.

PMID- 10924785
TI  - Use of cotton rats for preclinical evaluation of measles vaccines.
AB  - The continued prevalence and medical impact of measles worldwide has created
      interest in the development of new generations of measles vaccines. Monkeys can
      be used for preclinical testing of these vaccines. However, a more practical and
      less expensive animal model is highly desirable, particularly for initial vaccine
      development and evaluation. Cotton rats have been shown to support the
      replication of different strains of measles virus (MV), and thus may be useful
      for these purposes. To test this concept, the immunogenicity and protective
      efficacy of two standard (Moraten and trivalent measles, mumps, rubella) and four
      experimental (two recombinant ALVAC, one ISCOM subunit and live attenuated
      Edmonston-Zagreb) MV vaccines were evaluated in naive cotton rats, and cotton
      rats with passively acquired MV-specific neutralizing serum antibodies. All of
      the test vaccines were immunogenic and protected naive animals from pulmonary
      infection and viral dissemination. However, under the conditions utilized, only
      the Edmonston-Zagreb vaccine provided such protection to animals with significant
      levels of passively acquired MV-specific neutralizing antibodies. The results of
      these tests and the potential of using cotton rats as an animal model for
      preliminary testing of MV vaccines are discussed.

PMID- 10924786
TI  - Influence of antigenic forms and adjuvants on protection against a lethal
      infection of Aujeszky's disease virus.
AB  - The influence of antigenic forms and adjuvant types on protection against a
      lethal infection of Aujeszky's disease virus (ADV) in mice was investigated.
      Antiviral IgG2a antibody response against particulate (inactivated ADV) and
      soluble antigen (ADV solubilized with deoxychorate-Na) in approximate order of
      extent was ISA70>QS-21>positively charged liposome>negatively charged
      liposome>weak negatively charged liposome>ISA25>lablabside F saponin>aluminum
      phosphate gel>non adjuvant. Particulate antigen induced higher IgG2a antibody
      production than soluble antigen. Particulate antigen combined with ISA70, ISA25
      or positively charged liposome gave 100, 50 and 40% protection to mice,
      respectively. In contrast, soluble antigen plus ISA70 conferred 30% protection on
      mice. Immunogens using the other adjuvants gave </=20% protection to mice. These
      results indicate that a combination of particulate antigen and an appropriate
      adjuvant effectively induces the production of antiviral IgG2a antibody and
      provides protection against a lethal ADV infection in mice.

PMID- 10924787
TI  - Evaluation of immunogenicity and protective efficacy of carrier-free Plasmodium
      falciparum R23 antigen in pre-exposed saimiri sciureus monkeys.
AB  - We have reported previously that the recombinant Glutathione S-transferase GTR23,
      induced protection after immunisation of naive or previously exposed Saimiri
      monkeys. We investigated the immunogenicity of carrier-free R23 repeats in pre
      exposed animals in two adjuvant formulations. Three of five monkeys immunised
      with alum-formulated repeats and one of two animals immunised with the
      Polyalphaolefine formulation produced high titres of cytophilic antibodies with a
      primary type kinetics, indicating that the anti-P. falciparum antibodies present
      on the day of challenge were R23-specific. The four responders in R23-specific
      antibodies were protected against a challenge infection with the virulent FUP/SP
      strain. The other three animals failed to respond to immunisation and experienced
      an infection that required drug treatment. Unlike the other three animals that
      experienced an infection requiring drug treatment. These experiments support
      further development of the R23 repeats as a vaccine candidate.

PMID- 10924788
TI  - The immune response to a polyoma virus replicon-based DNA vaccine.
AB  - DNA vaccination has proven to be effective against a number of tumours and
      microbial diseases. As DNA vaccines are unable to replicate, plasmid copy number
      per cell is dependent on in vivo transfection efficiency, which is usually quite
      low. Consequently, immune responses generated are likely to be sub-optimal due to
      low antigen expression levels in transfected cells. During this study,
      replicating DNA vaccines delivered intra-epidermally by gene gun, were assessed
      for their ability to more efficiently generate immune responses in mice. The data
      demonstrate that, using a polyoma virus-based system of replication, 10-fold less
      DNA expressing the haemagglutinin gene of influenza virus, was required to
      stimulate a humoral immune response, compared to an equivalent non-replicating
      vaccine. This observation suggests that the use of replicating DNA vaccines in
      some delivery systems may enhance the effectiveness of immune responses.

PMID- 10924790
TI  - Evidence of cross-protection within Leptospira interrogans in an experimental
      model.
AB  - Killed whole-cell preparations were used as bacterins against leptospirosis. As
      this type of protection is considered to be serogroup-specific, several
      serogroups were added to the usual vaccines, and the most pathogenic serovar was
      chosen for each group. Different leptospire extracts were evaluated for their
      protective capacity against acute lethal leptospirosis in gerbils (Meriones
      unguiculatus). Total extracts induced complete protection against homologous
      challenges and partial protection against heterologous challenges. LPS fractions
      protected against homologous but not heterologous challenges, whereas protein
      extract induced significant protection against both types of challenge. Thus,
      cross-protection within L. interrogans was related to the protein extract.

PMID- 10924789
TI  - IEM101, a naturally attenuated Vibrio cholerae strain as carrier for genetically
      detoxified derivatives of cholera toxin.
AB  - Two mutants of cholera toxin (CTS106 containing a Pro106-->Ser substitution and
      CTK63 containing a Ser63-->Lys substitution) with greatly reduced or no toxicity
      respectively, were expressed in the naturally attenuated IEM101 Vibrio cholerae
      strain (El Tor, Ogawa) which does not express cholera toxin (CT). Expression was
      driven by the natural promoter of CT, or by a promoter known to induce strong in
      vivo expression such as nirB. In the rabbit ileal loop assay, where 10(4) wild
      type bacteria were sufficient to induce fluid accumulation, 10(9) IEM101
      expressing CTS106 bacteria were needed to induce some fluid accumulation, while
      IEM101 expressing CTK63 was inactive, even when 10(10) cells were used. When used
      to immunize mice intranasally, all bacteria induced vibriocidal antibodies;
      however, anti-CT antibodies were not induced by bacteria expressing low levels of
      CTK63 under the control of the ct promoter. Anti-CT antibodies were successfully
      induced by bacteria expressing high levels of CTK63 under the control of the nirB
      promoter, or by bacteria expressing low levels of CTS106. These data show that
      antibodies against cholera toxin can be induced in vivo by high level expression
      of a non toxic mutant, or by using a mutant with residual ADP-ribosyltransferase
      activity. In conclusion, we have shown that IEM101, a naturally attenuated Vibrio
      strain known to be safe and immunogenic in humans, can be engineered to express
      immunogenic levels of CTK63, and may represent a good candidate for vaccination
      against cholera.

PMID- 10924791
TI  - Interleukin-18 modulates immune responses induced by HIV-1 Nef DNA prime/protein
      boost vaccine.
AB  - Many different HIV-1 vaccine strategies have been developed, but as yet none has
      been completely successful. Promising results from combined DNA prime/protein
      boost vaccines have been reported. Specific immune responses generated by DNA
      vaccines can be modulated by the co-delivery of genes coding for cytokines. In
      this study, we have used the intradermal route by needle injection of a plasmid
      coding for the HIV-1 Nef accessory protein. We show that DNA prime/protein boost
      vaccine combinations increase the humoral and cellular immune responses against
      HIV-1 Nef and that the co-injection of DNA encoding Interleukin-18 (IL-18)
      modulates the specific immune response towards a Th1 type.

PMID- 10924792
TI  - Multi-epitope schistosome vaccine candidates tested for protective immunogenicity
      in mice.
AB  - The major challenge in the development of anti-schistosome vaccines is to use
      defined antigens to stimulate an appropriate immune response that leads to
      resistance. Several promising candidate vaccine antigens including the glycolytic
      enzyme triose-phosphate isomerase (SmTPI), a 28 kDa glutathione-S-transferase
      (Sm28), the myofibrilar protein paramyosin (Sm97), an integral membrane protein
      (Sm23) and calpain (Smcalpain) have been characterised and their primary
      sequences derived for Schistosoma mansoni. Furthermore, sequences are available
      for synthetic peptides mimicking epitopes on these molecules capable of inducing
      schistosome-specific T- and B-cell responses. These schistosome vaccine
      candidates have generally been tested with varying degrees of success as single
      components, with only one report of the use of a multivalent antigen or multi
      epitope approach. We describe the assembly of multiple defined and different
      epitopes of S. mansoni into a variety of single covalent structures; these
      included a DNA vaccine encoding different epitopes in tandem, the polyprotein
      itself that is encoded by this DNA and branched synthetic peptide epitope-based
      polymers in which the individual epitopes are pendant from an inert backbone.
      Each of the vaccine constructs examined, with the exception of the DNA vaccine,
      generated antibodies that were capable of binding to a tandem sequence of the
      epitopes. Although these results were encouraging, none of the constructs
      protected animals from subsequent challenge infection, indicating that the immune
      responses elicited were inadequate or inappropriate for parasite killing in vivo.

PMID- 10924793
TI  - Inhibition of tetanus toxin fragment C binding to ganglioside G(T1b) by
      monoclonal antibodies recognizing different epitopes.
AB  - Anti-tetanus toxoid monoclonal antibodies would be useful in exploring the
      relationship of tetanus toxin structure to its function. Tetanus toxin fragment C
      has been shown to be responsible for binding to neurons via gangliosides. Eleven
      new and two previously derived monoclonal antibodies specific for tetanus toxin
      fragment C were shown to recognize five different fragment C epitopes, two of
      which were overlapping. Three of these epitopes participate in the binding to
      ganglioside G(T1b). One epitope was defined by a monoclonal antibody that did not
      inhibit the interaction between fragment C and ganglioside. This antibody
      however, was blocked from binding to fragment C by antibodies that were able to
      inhibit the fragment C-ganglioside interaction.

PMID- 10924794
TI  - Induction of antibody and T-cell responses by immunization with ISCOMS containing
      the 38-kilodalton protein of Mycobacterium tuberculosis.
AB  - In this study, we investigated the influence of different amounts of N
      (palmitoyloxy) succinimide (PA-NHS): attachment of lipid tails to the protein and
      Quil A on the immunogenicity of the 38-kDa mycobacterial protein incorporated
      into immunostimulating complexes (ISCOMS; 38-kDa ISCOMS). The addition of higher
      amounts of Quil A during the ISCOMS preparation increased the amount of protein
      incorporated into ISCOMS, whereas the use of higher amounts of PA did not
      influence this parameter. Low antibody responses were observed after primary
      immunization with all 38-kDa ISCOMS preparations which, however, strongly
      increased after booster injections. IgG2a is the major subclass IgG induced by
      these ISCOMS preparations. There were only slight differences between the various
      ISCOMS formulations in their capacity to induce cytotoxic T-lymphocytes (CTLs).
      Spleen cells primed with ISCOMS prepared with the highest amount of Quil A
      produced high levels of IFN-gamma after stimulation with T helper cell type one
      (Th1) peptide of the 38-kDa protein (aa 70-84), 38-kDa protein or purified
      protein derivate (PPD). Spleen cells primed with ISCOMS prepared with the lowest
      amount of Quil A only substantial IFN-gamma levels were detected after
      stimulation with 38-kDa protein. IL-4 secretion was very low or not detectable
      with all ISCOM preparations. These results therefore demonstrated that all 38 kDa
      ISCOMS preparations were: (1) immunogenic by inducing antibodies, Th1 and CTL
      responses; (2) that the way in which the ISCOMS were prepared, e.g. the amount of
      Quil A used, modulates the epitope specificity of the Th1 response.

PMID- 10924795
TI  - Adjuvant effects of sulfolipo-cyclodextrin in a squalane-in-water and water-in
      mineral oil emulsions for BHV-1 vaccines in cattle.
AB  - The antibody and cell mediated immune responses induced by BHV-1 were analysed in
      cattle after vaccination and challenge exposure to the virulent strain LA of BHV
      1. Animals were vaccinated intramuscularly (IM) with inactivated virus vaccines
      against BHV-1 containing either a water in mineral oil adjuvant (W/O), a water in
      mineral oil adjuvant plus Avridine (W/O+Avridine) or sulfolipo-cyclodextrin in
      squalane in-water emulsion (SL-CD/S/W). No significant differences were
      registered in the antibody response induced by the three evaluated vaccines.
      However, the BHV-1 specific cell-mediated immunite response was stronger and
      appeared earlier when SL-CD/S/W was included in the formulation. The efficacy of
      the vaccines was also evaluated after intranasal challenge of the calves with a
      virulent BHV-1 LA strain. Animals vaccinated with SL-CD/S/W had reduced virus
      excretion and clinical symptoms compared with the mock-vaccinated animals.
      Comparison of levels of BHV-1 specific IgG2 and IgG1 with virus shedding revealed
      that, regardless of the adjuvant administered, animals showing BHV-1 specific
      IgG2/IgG1 ratios higher than 1 were those with a significant lower number of
      individuals shedding virus. Additionally, animals vaccinated with SL-CD/S/W
      presented no post-vaccinal reactions. These factors, combined with the higher
      efficacy and the ease of manipulation of the biodegradable oil, makes the vaccine
      formulated with this new adjuvant an important contribution for the veterinary
      vaccines industry.

PMID- 10924796
TI  - Recombinant RNA replicons derived from attenuated Venezuelan equine encephalitis
      virus protect guinea pigs and mice from Ebola hemorrhagic fever virus.
AB  - RNA replicons derived from an attenuated strain of Venezuelan equine encephalitis
      virus (VEE), an alphavirus, were configured as candidate vaccines for Ebola
      hemorrhagic fever. The Ebola nucleoprotein (NP) or glycoprotein (GP) genes were
      introduced into the VEE RNA downstream from the VEE 26S promoter in place of the
      VEE structural protein genes. The resulting recombinant replicons, expressing the
      NP or GP genes, were packaged into VEE replicon particles (NP-VRP and GP-VRP,
      respectively) using a bipartite helper system that provided the VEE structural
      proteins in trans and prevented the regeneration of replication-competent VEE
      during packaging. The immunogenicity of NP-VRP and GP-VRP and their ability to
      protect against lethal Ebola infection were evaluated in BALB/c mice and in two
      strains of guinea pigs. The GP-VRP alone, or in combination with NP-VRP,
      protected both strains of guinea pigs and BALB/c mice, while immunization with NP
      VRP alone protected BALB/c mice, but neither strain of guinea pig. Passive
      transfer of sera from VRP-immunized animals did not confer protection against
      lethal challenge. However, the complete protection achieved with active
      immunization with VRP, as well as the unique characteristics of the VEE replicon
      vector, warrant further testing of the safety and efficacy of NP-VRP and GP-VRP
      in primates as candidate vaccines against Ebola hemorrhagic fever.

PMID- 10924797
TI  - Chelation of aluminium by combining DFO and L1 in rats.
AB  - The hypothesis that two known chelators 1, 2-dimethyl-3-hydroxypyrid-4-one (L1)
      and desferrioxamine (DFO) might be more efficient as combined treatment than as
      monotherapies in removing aluminium from the body was tested in a new acute rat
      model. Five-week old female rats received chelators: L1 (p.o.), DFO (i.p.) or
      L1+DFO as 100 or 200 mg/kg dose half an hour after a single i.p. administration
      of 6 mg Al/kg body weight in the form of chloride. Serum aluminium concentration
      and urinary aluminium and iron excretions were determined by electrothermal or
      flame atomic absorption spectrometry. Both chelators were effective only at the
      higher dose level. While DFO was more effective than L1 in enhancing urinary
      aluminium excretion, L1 was more effective than DFO in enhancing urinary iron
      excretion. In the combined treatment group L1 did not increase the DFO effect on
      aluminium and DFO did not increase the effect of L1 on iron elimination. However,
      in this group a simultaneous increase in both aluminium and iron elimination was
      observed. Our results support the usefulness of this animal model for preliminary
      in vivo testing of aluminium chelators. Urinary values were more useful because
      of the high variability of serum results. Result of combined chelators treatment
      should be confirmed in a different experimental model before extrapolation to
      other systems. This testing procedure of course does not provide all the relevant
      answers for evaluating the efficiency of chelating agents in aluminium toxicity.

PMID- 10924798
TI  - Chronic combined exposure to cadmium and arsenic exacerbates nephrotoxicity,
      particularly in metallothionein-I/II null mice.
AB  - Cadmium (Cd) and arsenic (As) are important inorganic toxicants in the
      environment. Humans certainly have the potential to be exposed to the mixtures of
      Cd and As, but the toxicological interactions of these inorganic mixtures are
      poorly defined. Metallothionein (MT) is a cysteine-rich, metal-binding protein
      that plays an important role in Cd detoxication, but its role in As toxicity is
      less certain. To examine the role of MT in Cd- and/or As-induced nephrotoxicity,
      MT-I/II-knockout (MT-null) mice and background-matched wild-type (WT) mice were
      fed CdCl(2) (100 ppm Cd) in the diet, NaAsO(2) (22.5 ppm As) in the drinking
      water, or Cd plus As for 4 months. Subsequently, nephrotoxicity was examined by
      morphological and biochemical techniques. Chronic exposure to Cd produced more
      renal toxicity than As, and the combination of Cd and As produced even more renal
      injury than caused by either of the chemicals given alone. In mice receiving Cd
      plus As, proximal tubule degeneration and atrophy, glomerular swelling and
      interstitial fibrosis were more severe than those produced by either inorganic.
      Furthermore, lack of MT rendered MT-null mice more sensitive than WT mice to the
      nephrotoxicity produced by chronic Cd- and/or As-exposure. MT-null mice were
      especially susceptible to the toxicity produced by the combination of Cd and As,
      as evidenced by decreased body weight, enzymuria, glucosuria, proteinuria and
      nephropathy. In conclusion, this study indicates that As may potentiate Cd
      nephrotoxicity during the long-term, combined exposure, and that intracellular MT
      plays a role in decreasing the nephropathy of combined exposure to Cd and As.

PMID- 10924799
TI  - Endotoxin pretreatment protects against the hepatotoxicity of acetaminophen and
      carbon tetrachloride: role of cytochrome P450 suppression.
AB  - Bacterial endotoxin (lipopolysaccharide, LPS) is known to potentiate the toxicity
      of many hepatotoxicants. However, exposure to a sublethal dose of LPS renders
      animals tolerant to a lethal dose of LPS, and protects against the toxicity of
      some chemicals. This study was designed to examine the effects of LPS
      pretreatment on acetaminophen- and carbon tetrachloride (CCl(4))-induced liver
      injury in LPS-sensitive C3H/OuJ and LPS-resistant C3H/HeJ mice. Pretreatment of
      male C3H/OuJ mice with a single injection of LPS (0. 1 mg/kg, ip, for 24 h)
      protected against the hepatotoxic effects of acetaminophen (400 mg/kg) and carbon
      tetrachloride (CCl(4), 30 mg/kg), as indicated by serum alanine aminotransferase
      activity. In contrast, pretreatment of C3H/HeJ mice with 0.1 or 10 mg/kg LPS
      afforded no protection against the hepatotoxic effects of acetaminophen and
      CCl(4). In an attempt to determine the mechanism of LPS-induced protection
      against acetaminophen- and CCl(4)-induced hepatotoxicity in C3H/OuJ mice, liver
      cytochrome P450 was determined 24 h after LPS injection. LPS treatment caused a
      26% decrease in total P450 content in C3H/OuJ but not in C3H/HeJ mice. CYP3A
      catalized testosterone 6 beta-, 2 beta-, and 15 beta-hydroxylation was decreased
      40% by LPS only in C3H/OuJ mice. To determine whether the differences to LPS
      response in the two stains of mice is mediated by a strain-related difference in
      the release of cytokines, mice were pretreated with interleukin-1 (IL-1 alpha, 5
      x 10(5) U/mouse), and the hepatoprotection and hepatic P450 enzymes were
      examined. IL-1 alpha pretreatment equally protected against the hepatotoxicity of
      acetaminophen and CCl(4) in both strains, and suppressed the total microsomal
      P450 and P450 enzyme-catalyzed testosterone hydroxylation to a similar extent. In
      conclusion, LPS pretreatment suppressed hepatic cytochrome P450 enzymes and
      protected against the hepatotoxicity of acetaminophen and CCl(4) in LPS-sensitive
      C3H/OuJ mice, but not in LPS-refractory C3H/HeJ mice. This protective effect of
      LPS appears to be mediated through the release of cytokines such as IL-1 alpha,
      which in turn suppresses the cytochrome P450 responsible for the activation of
      acetaminophen and CCl(4) to reactive metabolites.

PMID- 10924800
TI  - UDS induction by an array of standard carcinogens in human and rodent
      hepatocytes: effect of cryopreservation.
AB  - The UDS induction assay with primary hepatocytes as the target cells is a
      determinative assay for chemical carcinogens. This assay is, however, limited to
      the availability of freshly prepared liver cells. A cryopreservation technique
      for liver cells has recently been described. Frozen cells have been shown to
      retain a variety of enzyme activities essential for xenobiotic metabolism after
      being thawed. In the present investigation, 19 direct or indirect-acting
      carcinogens were tested with respect to their capacity to induce DNA repair in
      primary as well as cryopreserved human and rat hepatocytes. Cryopreserved cells
      yielded results that were essentially indistinguishable from fresh cells. Only
      marginal differences were observed between hepatocytes of rat or human origin.
      These results demonstrate the suitability of cryopreserved hepatocytes as
      indicator cells for the study of UDS induction to discover possible
      carcinogenicity in chemicals.

PMID- 10924801
TI  - Comparative evaluation of the combined osteolathyritic effects of two nitrile
      combinations on xenopus embryos.
AB  - Two nitrile combinations, beta-aminopropionitrile (beta APN) with
      aminoacetonitrile (AAN) and betaAPN with beta APN (as a sham combination), were
      evaluated using the frog embryo mixture toxicity assay to determine their
      combined osteolathyritic effects and to compare the results with theoretical
      effects for two combined effects models. In separate tests each nitrile was
      tested with copper sulfate to determine the importance of copper in
      osteolathyrogen-induced disruption of connective tissue cross-linking. Frog
      embryos (Xenopus laevis) were exposed for 96 h, with daily solution removal and
      replacement. Preserved tadpoles were evaluated for osteolathyritic lesions. For
      the nitrile:nitrile combinations, the chi(2) goodness-of-fit test was used to
      compare the resulting mixture-response curves to theoretical curves for dose
      addition and independence. For beta APN with AAN, the combined osteolathyritic
      effect for five of the seven mixture curves generated was greater than expected
      for each of the combined effects models. For beta APN with beta APN, the combined
      effect for all seven mixture curves was consistent with dose-addition, the
      combined effect expected for chemicals inducing toxicity by the same mechanism.
      For the nitrile:copper combinations, the EC(50) for beta APN-induced
      osteolathyrism was increased two- to threefold (i.e. made less toxic) by co
      administration with copper sulfate, while the EC(50) for AAN-induced
      osteolathyrism was unchanged. The results are consistent with the idea that beta
      APN and AAN induce osteolathyrism, at least in part, by different mechanisms.

PMID- 10924802
TI  - Increased airway responsiveness after skin sensitisation to 3-carene, studied in
      isolated guinea pig lungs.
AB  - Inhalation of 3-carene has been shown to induce bronchoconstriction in
      concentrations not far from the threshold limit value. In this study, one group
      of guinea-pigs were sensitised by dermal exposure to 3-carene according to the
      modified Cumulative Contact Enhancement Test protocol and another group of
      animals was used as controls. Lungs from the skin-sensitised and control guinea
      pigs were perfused with diluted autologous blood (13 ml blood/87 ml buffer) and
      exposed to 3-carene at an air concentration of 3000 mg/m(3). In both groups there
      was a reduction in compliance and conductance but this reduction was
      significantly (P<0.05) more pronounced (2.5-3 times) in lungs obtained from
      sensitised animals than from control animals. In a previous study with similar
      design, but with plain buffer instead of diluted autologous blood as perfusate,
      we found no statistically significant difference in lung bronchoconstriction.
      Thus, it is concluded that skin sensitisation can increase lung reactivity to 3
      carene and that important mediators of this effect seem to be present in the
      blood.

PMID- 10924803
TI  - Suppressed oxidant-induced apoptosis in cadmium adapted alveolar epithelial cells
      and its potential involvement in cadmium carcinogenesis.
AB  - Apoptosis involves a series of genetically programmed events associated with
      endonucleolytic cleavage of DNA. This process is triggered by a variety of
      agents, including oxidants such as hydrogen peroxide (H(2)O(2)) and it plays a
      key role in eliminating pre-neoplastic cells from the lung. Failure to do so
      could favor tumor promotion. The current study demonstrated that alveolar
      epithelial cells, adapted to cadmium (CdCl(2)) by repeated in vitro exposure,
      exhibit lower levels of H(2)O(2)-induced apoptosis than similarly challenged non
      adapted cells. An immunologic assay, measuring cytoplasmic histone-associated DNA
      fragments, indicated maximal apoptosis 24 h after exposure to 400 microM
      H(2)O(2). Non-adapted cells showed a 13-fold increase in oxidant-induced
      apoptosis while Cd-adapted cells had only a 4-fold elevation. A terminal
      deoxyribonucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method
      was used to assess the percentage of cells with DNA breaks consistent with
      apoptosis. Cd-adapted and non-adapted cells that were not exposed to H(2)O(2) did
      not differ in TUNEL positivity. However, after H(2)O(2) treatment, the percentage
      of TUNEL positive cells was 4-fold higher in non-adapted cultures than in adapted
      ones. Suppression of oxidant-induced apoptosis is due, in part, to up-regulation
      in the gene expression of several resistance factors including metallothioneins
      (MT-1 and MT-2), glutathione S-transferases (GST-alpha and GST-pi), and gamma
      glutamylcysteine synthetase catalytic subunit (gamma-GCS). These steady-state
      mRNA changes, determined by Northern blotting, were accompanied by increased
      levels of MT and gamma-GCS protein, GST activity, and glutathione (GSH).
      Suppressed oxidant-induced apoptosis, resulting at least in part from these
      response modifications, could leave pre-neoplastic or neoplastic cells alive,
      favor clonal expansion, and ultimately lead to cancer development.

PMID- 10924804
TI  - Cortical representation of pain: functional characterization of nociceptive areas
      near the lateral sulcus.
AB  - Many lines of evidence implicate the somatosensory areas near the lateral sulcus
      (Sylvian fissure) in the cortical representation of pain. Anatomical tracing
      studies in the monkey show nociceptive projection pathways to the vicinity of the
      secondary somatosensory cortex in the parietal operculum, and to anterior parts
      of insular cortex deep inside the Sylvian fissure. Clinical observations
      demonstrate alterations in pain sensation following lesions in these two areas in
      human parasylvian cortex. Imaging studies in humans reveal increased blood flow
      in parasylvian cortex, both contralaterally and ipsilaterally, in response to
      painful stimuli. Painful stimuli (such as laser radiant heat) evoke potentials
      with a scalp maximum at anterior temporal positions (T3 and T4). Several dipole
      source analyses as well as subdural recordings have confirmed that the earliest
      evoked potential following painful laser stimulation of the skin derives from
      sources in the parietal operculum. Thus, imaging and electrophysiological studies
      in humans suggest that parasylvian cortex is activated by painful stimuli, and is
      one of the first cortical relay stations in the central processing of these
      stimuli. There is mounting evidence for closely located but separate
      representations of pain (deep parietal operculum and anterior insula) and touch
      (secondary somatosensory cortex and posterior insula) in parasylvian cortex. This
      anatomical separation may be one of the reasons why single unit recordings of
      nociceptive neurons are scarce within regions comprising low-threshold
      mechanoreceptive neurons. The functional significance (sensory-discriminative,
      affective-motivational, cognitive-evaluative) of the closely spaced parasylvian
      cortical areas in acute and chronic pain is only poorly understood. It is likely
      that some of these areas are involved in sensory-limbic projection pathways that
      may subserve the recognition of potentially tissue damaging stimuli as well as
      pain memory.

PMID- 10924805
TI  - The role of sympathetic nerve blocks in herpes zoster and postherpetic neuralgia.
AB  - The most common complication of herpes zoster in immunocompetent patients is
      postherpetic neuralgia (PHN). Sympathetic blocks have been traditionally used for
      patients with herpes zoster and PHN with three different therapeutic goals: pain
      relief during acute herpes zoster, pain relief during PHN, and prevention of PHN
      by treating patients with acute zoster. The role of sympathetic blocks in herpes
      zoster and PHN remains controversial due to methodologic shortcomings in
      published studies and the limited current understanding of the role of the
      sympathetic nervous system in mediating pain. Current theories of the
      pathophysiology of PHN, the role of the sympathetic nervous system in herpes
      zoster and PHN, and published studies investigating use of sympathetic nerve
      blocks in herpes zoster and PHN are reviewed.

PMID- 10924806
TI  - Noxious stimulation increases glutamate and arginine in the periaqueductal gray
      matter in rats: a microdialysis study.
AB  - The periaqueductal gray matter (PAG) is an important center in the modulation of
      behavioral responses during nociception and stress. In the present experiment,
      extracellular excitatory amino acid overflow in the PAG was measured every 30 s
      during noxious stimulation. A combination of in vivo brain microdialysis in
      freely moving rats and capillary zone electrophoresis with laser induced
      fluorescence detection allowed us to detect short lasting changes of excitatory
      amino acid in dialysates. A formalin injection in the hindpaw of the rat
      increased glutamate, arginine and aspartate concentration in PAG dialysates. This
      increase was calcium and nerve impulse-dependent, suggesting neuronal and glial
      origin of glutamate and arginine, respectively. Handling, pinching or saline
      injection in the hind paw did not increase glutamate showing that this
      neurochemical phenomenon is related to painful and persistent noxious
      stimulation. The results suggest that a rapid excitation of the PAG occurs during
      noxious stimulation. The role of glutamate and arginine in analgesia is
      discussed.

PMID- 10924807
TI  - Irritable bowel syndrome patients show altered sensitivity to exogenous opioids.
AB  - Alterations in activation of pain modulation systems may play a role in the
      pathophysiology of irritable bowel syndrome (IBS). However, little is known about
      the effects of exogenous opioids on the perceptual and autonomic responses to
      aversive visceral stimulation. The aim of the study was to evaluate the effect of
      the mu opioid-preferring analgesic fentanyl (FEN), given intravenously, on
      perceptual and autonomic responses to rectal distension. Ten IBS patients and ten
      normal subjects received, on separate days, either high dose (HD) fentanyl (112
      microg bolus followed by 0.04 microg/kg per min infusion), low dose (LD) fentanyl
      (56 microg bolus followed by 0.02 microg/kg per min) or normal saline (SAL) (50
      cc bolus followed by 45 cc/h infusion). Perception thresholds for discomfort and
      pain during rectal distension were assessed using a tracking paradigm. Intensity
      and unpleasantness ratings of the distensions, and cardiac autonomic parameters
      were assessed during randomly delivered rectal stimuli. Effects of FEN on rectal
      compliance and tone as well as mental status were also assessed. IBS patients had
      lower perceptual thresholds for discomfort and pain under control conditions. FEN
      dose-dependently increased the perception thresholds in both healthy control
      subjects and in IBS patients with a greater relative efficacy in IBS patients
      than in normal subjects. IBS patients used significantly higher unpleasantness
      ratings of rectal stimuli compared to healthy controls, but showed no difference
      in the sensory intensity rating of the stimulus. FEN decreased both intensity and
      unpleasantness ratings for IBS and normals. FEN lowered cardiosympathetic tone in
      normal subjects but had no effect on IBS patients. FEN had no effect on rectal
      tone or compliance. FEN dose-dependently attenuates the perception of phasic
      rectal distension and affects unpleasantness ratings during random fixed rectal
      distension, with a greater relative efficacy for this antinociceptive effect in
      IBS patients. These findings support the hypothesis that IBS patients may have an
      altered central release of endogenous opioids in response to visceral
      stimulation.

PMID- 10924808
TI  - Spared nerve injury: an animal model of persistent peripheral neuropathic pain.
AB  - Peripheral neuropathic pain is produced by multiple etiological factors that
      initiate a number of diverse mechanisms operating at different sites and at
      different times and expressed both within, and across different disease states.
      Unraveling the mechanisms involved requires laboratory animal models that
      replicate as far as possible, the different pathophysiological changes present in
      patients. It is unlikely that a single animal model will include the full range
      of neuropathic pain mechanisms. A feature of several animal models of peripheral
      neuropathic pain is partial denervation. In the most frequently used models a
      mixture of intact and injured fibers is created by loose ligation of either the
      whole (Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces
      disorders of pain sensation like those seen in man. Pain 1988;33:87-107) or a
      tight ligation of a part (Seltzer Z, Dubner R, Shir Y. A novel behavioral model
      of neuropathic pain disorders produced in rats by partial sciatic nerve injury.
      Pain 1990;43:205-218) of a large peripheral nerve, or a tight ligation of an
      entire spinal segmental nerve (Kim SH, Chung JM. An experimental model for
      peripheral neuropathy produced by segmental spinal nerve ligation in the rat.
      Pain 1992;50:355-363). We have developed a variant of partial denervation, the
      spared nerve injury model. This involves a lesion of two of the three terminal
      branches of the sciatic nerve (tibial and common peroneal nerves) leaving the
      remaining sural nerve intact. The spared nerve injury model differs from the
      Chung spinal segmental nerve, the Bennett chronic constriction injury and the
      Seltzer partial sciatic nerve injury models in that the co-mingling of distal
      intact axons with degenerating axons is restricted, and it permits behavioral
      testing of the non-injured skin territories adjacent to the denervated areas. The
      spared nerve injury model results in early (<24 h), prolonged (>6 months), robust
      (all animals are responders) behavioral modifications. The mechanical (von Frey
      and pinprick) sensitivity and thermal (hot and cold) responsiveness is increased
      in the ipsilateral sural and to a lesser extent saphenous territories, without
      any change in heat thermal thresholds. Crush injury of the tibial and common
      peroneal nerves produce similar early changes, which return, however to baseline
      at 7-9 weeks. The spared nerve injury model may provide, therefore, an additional
      resource for unraveling the mechanisms responsible for the production of
      neuropathic pain.

PMID- 10924809
TI  - Central administration of methotrexate reduces mechanical allodynia in an animal
      model of radiculopathy/sciatica.
AB  - We have recently reported that injury to a lumbar root in a rat model of
      radiculopathy produces spinal glial activation associated with elevated
      proinflammatory cytokines. Based on our hypothesis that central neuroinflammatory
      processes may manifest clinically as radicular pain, we undertook pharmacological
      intervention using the immunosuppressive agent methotrexate (MTX). The L5 lumbar
      spinal root (central to the dorsal root ganglia) was exposed unilaterally and
      loosely constricted with chromic gut. In the prevention (phase I) study, MTX was
      administered intrathecally (1 mg/kg) and around the spinal root (1 mg/kg) at
      surgery and at days 2 and 4 postsurgery (group A). Saline injection was employed
      for the control group (group B). Sham operated animals were administered MTX to
      determine the potential for behavioral/neural side effects (group C). In the
      existing pain paradigm (phase II) study, the experiment was extended to day 14
      with three additional groups. The same dose and method of delivery of MTX or
      saline was administered as in phase I in the first week on days 0, 2, and 4 and
      in the second week on days 7, 9, and 11 postsurgery. To measure the effects of
      MTX on existing behaviors saline was administered in the first week and MTX
      during the second (group D; Saline:MTX). The control group received saline during
      both weeks (group E; Saline:Saline). To examine the possible recurrence of
      radicular pain after MTX termination, MTX was given in the first week and saline
      in the second (group F; MTX:Saline). Gait disturbance and mechanical allodynia
      (using von Frey filaments) were assessed up to day 7 in the prevention study
      (Phase I) and day 14 in the existing pain paradigm (Phase II). The L5 spinal cord
      segments were harvested for assessment of immunohistochemical glial activation
      using the antibodies OX-42 (microglial marker) and glial fibrillary acidic
      protein (GFAP: astrocytic marker) and for the presence of Major
      Histocompatibility Complex (MHC) Class II expression. Group C (Sham+MTX) did not
      demonstrate any evidence of gait disturbance or mechanical allodynia after MTX
      administration. The rats in group B (Surgery+Saline) demonstrated mechanical
      allodynia from one day postsurgery to the time of euthanization. When allodynia
      was assessed using the 12 g von Frey filament, the MTX treated rats in group A
      showed significantly decreased mechanical allodynia as compared to the saline
      treated rats (group B) (repeated measured ANOVA, P<0.0001). In the phase II
      study, the rats in group D (Saline:MTX) and E (Saline:Saline) showed robust
      allodynia in the first week after the surgery. In the second week, mechanical
      allodynia significantly decreased in group D, while mechanical allodynia
      continued in the saline treated group (repeated measured ANOVA, P=0.0121).
      Allodynia was significantly attenuated in group F (MTX: Saline) as compared to
      the response in groups D and E at day 7 (one-way ANOVA, P<0.0001) and remained
      significantly lower as compared to group E up to day 11 postsurgery (one-way
      ANOVA, P9=0. 0013: P11=0.0048). OX-42 and GFAP expression were elevated in the
      gray matter of the L5 spinal section in all groups that underwent the root
      ligature with chromic gut (Groups A, B, D-F). There were no significant
      differences in glial activation between the groups. However, spinal expression of
      MHC II was markedly reduced in the MTX treated group as compared with the saline
      treated group. The exact mechanism of action of MTX in attenuating mechanical
      allodynia has not yet been elucidated. The present results indicate that MTX
      administration may offer a new treatment modality for radicular pain with or
      without disc herniation as well as directing new research into the development of
      novel immunomodulators for the treatment of chronic neuropathic and radicular
      pain.

PMID- 10924810
TI  - Effects of purinergic and adrenergic antagonists in a rat model of painful
      peripheral neuropathy.
AB  - In previous studies, pain behaviors produced in the spinal nerve ligation rat
      model of neuropathic pain were partly reduced by surgical lumbar sympathectomy.
      However, systemic injection of phentolamine, an alpha-adrenoceptor blocker, was
      not effective in reducing pain behaviors, at least in the Sprague-Dawley strain
      of rats. This suggests that sympathectomy removes not only adrenoceptor function
      but also other factors that must contribute importantly to the generation of
      neuropathic pain behaviors. Since the purinergic substance adenosine 5'
      triphosphate (ATP) is known to be co-released with norepinephrine (NE) from the
      sympathetic nerve terminals, we hypothesized that ATP might be involved in the
      sympathetic dependency of neuropathic pain. The present study tested this
      hypothesis by examining the effects of systemic injection of an adrenoceptor
      blocker (phentolamine), a purinoceptor blocker (suramin), and a combination of
      these two on behavioral signs of mechanical allodynia in the spinal nerve
      ligation model of neuropathic pain. The results of the present study showed two
      novel findings. First, the mechanical hypersensitivity (allodynia) resulting from
      the L5/6 spinal nerve ligation can be reduced either by sympathetic block
      accomplished by application of a local anesthetic or by surgical sympathectomy of
      the L2-L6 sympathetic ganglia. Second, suramin (at 100 mg/kg, i.p.) can reduce
      mechanical hypersensitivity in neuropathic rats when given in combination with 5
      mg/kg of phentolamine. This effect was observed in a subset of neuropathic rats,
      and the drug responses were consistent in repeated treatments within the animal
      group. Neither phentolamine nor suramin changed the mechanical sensitivity of
      neuropathic rats when given alone. The data suggest that the purinergic substance
      ATP is co-released with NE from sympathetic nerve terminals and these two are
      together involved, at least in part, in the maintenance of the sympathetically
      dependent component of pain behaviors in some neuropathic rats.

PMID- 10924811
TI  - Differential effects of antisense oligodeoxynucleotides directed against
      g(zalpha) and g(oalpha) on antinociception produced by spinal opioid and alpha(2)
      adrenergic receptor agonists.
AB  - The present studies assessed the role of G(zalpha) and G(oalpha) in spinal
      alpha(2) adrenergic receptor agonist-induced antinociception, as well as in
      antinociceptive synergism between spinal morphine and clonidine. Mice were
      pretreated with a single intrathecal (i.t.) injection of artificial cerebrospinal
      fluid (ACSF), antisense oligodeoxynucleotide(s) (ODN) directed against G(zalpha)
      or G(oalpha), or nonsense ODN. After 48 h, the antinociceptive effects expressed
      as per cent maximal possible effect (% MPE) of either i.t. morphine alone,
      clonidine alone or coadministered morphine plus clonidine, were evaluated in the
      tail flick test. Antisense ODN to G(zalpha) attenuated clonidine- but not
      morphine-induced antinociception. The ED(50) (95% confidence interval) value for
      clonidine in ACSF pretreated mice was 6.3 (4.9-8.1) nmol, and in nonsense ODN
      pretreated mice, it was 4.2 (2.8-6.3) nmol. However, in the G(zalpha) antisense
      ODN pretreated mice, the highest dose clonidine tested (50 nmol) produced only
      41+/-8.5% MPE. Antisense ODN to G(zalpha) also blocked antinociception produced
      by i.t. UK14, 304 (alpha(2) adrenergic receptor agonist) and [D-Pen(2), D-Pen(5)]
      enkephalin (DPDPE) (delta opioid receptor agonist), whereas it failed to
      attenuate i.t. Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol (DAMGO)- (mu opioid receptor
      agonist) and U50-488 (kappa opioid receptor agonist) -induced antinociception.
      Pretreatment with antisense ODN to G(oalpha) attenuated both morphine and
      clonidine induced antinociception and did not affect synergism between the
      agonists. These results suggest that spinal G(o)alpha mediates antinociception
      produced by both clonidine and morphine while G(zalpha) mediates alpha(2)
      adrenergic and delta opioid receptor mediated antinociception, but not
      antinociception produced by mu or kappa opioid agonists.

PMID- 10924812
TI  - Differential effects of spinal (R)-ketoprofen and (S)-ketoprofen against signs of
      neuropathic pain and tonic nociception: evidence for a novel mechanism of action
      of (R)-ketoprofen against tactile allodynia.
AB  - The spinal activity of racemic ketoprofen and its enantiomers in models of
      neuropathic and tonic pain was explored in rats. Tactile allodynia and thermal
      hyperalgesia were induced by tight ligation of the L(5)/L(6) spinal nerves. Tonic
      pain was modeled by the formalin-induced flinch response. The spinal injection of
      (S)-ketoprofen alone or of morphine alone did not produce antiallodynic activity.
      A 1:1 combination of these drugs produced a robust dose-dependent antiallodynic
      action, consistent with previous observations where (S)-ketorolac combined with
      morphine also produced antiallodynia. (R)-ketoprofen given alone spinally
      produced a dose-dependent antiallodynia, but its activity was not augmented by
      spinal morphine. Conversely, (S)-ketoprofen, but not (R)-ketoprofen, blocked the
      second phase of the formalin-induced flinch response; neither enantiomer
      significantly blocked phase one of the formalin response. Again, (S)-, but not
      (R)-ketoprofen, interacted synergistically with spinal morphine in suppressing
      the phase II formalin response. These results are consistent with a spinal COX
      inhibitory action of (S)-ketoprofen. These results also point to a novel, as yet
      undefined, mechanism of action of (R)-ketoprofen against signs of neuropathic
      pain that does not appear to involve COX inhibition. The ability to modulate
      tactile allodynia is of special interest as this represents an aspect of clinical
      neuropathic pain that is very difficult to treat adequately.

PMID- 10924813
TI  - Changes in the concentrations of amino acids in the cerebrospinal fluid that
      correlate with pain in patients with fibromyalgia: implications for nitric oxide
      pathways.
AB  - Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of
      patients with fibromyalgia syndrome (FMS). Because excitatory amino acids (EAAs)
      also appear to transmit pain, we hypothesized that CSF EAAs may be similarly
      involved in this syndrome. We found that the mean concentrations of most amino
      acids in the CSF did not differ amongst groups of subjects with primary FMS
      (PFMS), fibromyalgia associated with other conditions (SFMS), other painful
      conditions not exhibiting fibromyalgia (OTHER) or age-matched, healthy normal
      controls (HNC). However, in SFMS patients, individual measures of pain intensity,
      determined using an examination-based measure of pain intensity, the tender point
      index (TPI), covaried with their respective concentrations of glutamine and
      asparagine, metabolites of glutamate and aspartate, respectively. This suggests
      that re-uptake and biotransformation mask pain-related increases in EAAs.
      Individual concentrations of glycine and taurine also correlated with their
      respective TPI values in patients with PFMS. While taurine is affected by a
      variety of excitatory manipulations, glycine is an inhibitory transmitter as well
      as a positive modulator of the N-methyl-D-asparate (NMDA) receptor. In both PFMS
      and SFMS patients, TPI covaried with arginine, the precursor to nitric oxide
      (NO), whose concentrations, in turn, correlated with those of citrulline, a
      byproduct of NO synthesis. These events predict involvement of NO, a potent
      signaling molecule thought to be involved in pain processing. Together these
      metabolic changes that covary with the intensity of pain in patients with FMS may
      reflect increased EAA release and a positive modulation of NMDA receptors by
      glycine, perhaps resulting in enhanced synthesis of NO.

PMID- 10924814
TI  - Dorsal root section elicits signs of neuropathic pain rather than reversing them
      in rats with L5 spinal nerve injury.
AB  - Mechanical allodynia- and hyperalgesia-like behavior which develops in rats after
      L5 spinal nerve lesion has been suggested to be due to ectopic activity in the
      lesioned afferent neurons originating at the lesion site and/or in the dorsal
      root ganglion because it is eliminated by section of the dorsal root. Here we
      reevaluated the effect of a dorsal rhizotomy in rats after L5 spinal nerve
      lesion. Using calibrated von Frey hairs, paw withdrawal threshold to single
      stimuli and paw withdrawal incidence to repetitive stimulation were tested before
      and after nerve section. Neuropathic pain behavior of similar time course and
      magnitude also developed after cutting the L5 dorsal root, and L5 spinal nerve
      lesion-induced abnormal behavior could not be reversed by dorsal rhizotomy. The
      neuropathic pain behavior elicited by dorsal root section also developed when
      impulse conduction in the dorsal root axons was blocked during rhizotomy by a
      local anesthetic, i.e. when the immediate injury discharge was prevented from
      reaching the spinal cord. These results challenge the widely accepted idea that
      neuropathic pain behavior developing after spinal nerve lesion is dependent on
      ectopic activity in the lesioned afferent neurons. However, the present results
      do not rule out the possibility that after the two nerve lesions the mechanisms
      generating neuropathic pain behavior are different. After dorsal rhizotomy
      neuropathic pain behavior may be related to deafferentation whereas after spinal
      nerve lesion it may be caused by ectopic activity.

PMID- 10924815
TI  - Delayed onset muscle soreness: effect of an ischaemic block upon mechanical
      allodynia in humans.
AB  - The current study, for which ethical approval was obtained, was designed to
      assess the extent to which the tenderness or mechanical allodynia observed in
      delayed onset muscle soreness (DOMS) might be mediated by large diameter
      myelinated nerve fibres. Healthy human volunteers were recruited and randomly
      allocated to one of three groups: Normal-Control, Ischaemic-Control, and Test
      DOMS (total n=21; n=7 in each group). In the Normal-Control group, subjects
      attended on a single occasion for assessment of mechanical pain threshold (MPT)
      at standardized sites over the biceps brachii using a pressure algometer for a
      period of 20 min. In both remaining groups, ischaemia was induced in subjects'
      non-dominant upper limbs by elevation of the limb, followed by application of a
      sphygmomanometer cuff at a pressure of 250 mmHg. Throughout the period of the
      block (20-40 min), sharp/blunt sensation was assessed at regular intervals. MPT
      was assessed upon inflation of the cuff and reassessed at 10 min intervals until
      deflation. In the two ischaemic block groups, current level of pain was also
      monitored using a computerized visual analogue scale (VAS) at the beginning and
      end of the procedure. Subjects in the Test-DOMS group attended 48 h prior to
      ischaemic block for induction of DOMS using a standardized regime of eccentric
      exercise, but thereafter were treated in exactly the same manner as the Ischaemic
      Control group. Results showed a significant (P<0.05; ANOVA) increase in MPT in
      the Test-DOMS group by the 20 min point, corresponding to a 'normalization' of
      MPT; loss of the ability to distinguish between sharp/blunt sensation accompanied
      such changes. Parallel increases in reported pain were seen in both groups
      undergoing ischaemic block, indicating that the procedure did not alter
      nociception. While not definitive, these results suggest that altered processing
      of activity in large diameter (myelinated) afferents might underlie the
      mechanical allodynia observed in DOMS; thus, this is an area which warrants
      further investigation.

PMID- 10924816
TI  - Experimental tissue acidosis leads to increased pain in complex regional pain
      syndrome (CRPS).
AB  - The aim of this study was to investigate the role of local acidosis in the
      generation of pain in complex regional pain syndrome (CRPS). We investigated ten
      patients with CRPS of the upper extremity with a mean duration of the disease of
      43 weeks (range 4-280 weeks) and ten control subjects for sensitivity to infusion
      of fluids with low pH (pH 6.1). Another group of five CRPS patients and three
      healthy controls was investigated using the same protocol but neutral infusion
      fluid (pH 7.4). A motorized syringe pump was installed for a constant infusion of
      synthetic interstitial fluid (SIF, either acidified (pH 6.1) or neutral) into the
      skin at the back of the hands and, thereafter, into the interosseus I muscle on
      both sides. A flow rate of 30 ml/h was chosen for intradermal and 7.5 ml/h for
      intramuscular infusion over a period of 10 min. The magnitude of pain was rated
      on an electronic visual analogue scale. Patients were requested to give their
      ratings every 10 s during the whole stimulation period. The ratings were
      normalized as fractions of individual grand mean values. We found significantly
      increased pain perception during infusion of acidified SIF on the affected side
      in CRPS patients. Low pH fluid into the skin was significantly more painful
      between 4 and 6 min (ipsi 1.27 normalized rating (NR) (0. 19-1.94), contra 0.31
      NR (0.03-0.51), P<0.02) and between 8 and 10 min (ipsi 1.38 NR (0.19-1.94),
      contra 0.08 NR (0-0.27), P<0.03) on the affected side, while analysis over the
      whole stimulation period just failed to reach statistical significance (ipsi 281
      area under the curve (AUC) (187-834), contra 87 AUC (28-293), P=0.059). Low pH
      infusion into the muscle was significantly more painful on the affected side
      during the whole infusion time (ipsi 861 AUC (308-1377), contra 190 AUC (96-528),
      P<0.01). The quality of the deep pain during infusion into the muscle was
      described by the patients as very similar to the CRPS-related pain. In controls
      we found no side differences of pain intensity during low pH stimulation. Neutral
      SIF evoked no pain at all, neither in CRPS patients (ipsi 0 AUC, contra 0 AUC)
      nor in healthy controls. Our results suggest that hyperalgesia to protons is
      present in patients with CRPS. Further, we could demonstrate that pain is not
      only restricted to the skin but is also generated in deep somatic tissue of the
      affected limb.

PMID- 10924817
TI  - Foreword

PMID- 10924818
TI  - Basic aspects of frozen storage of semen.
AB  - Basic concepts of cryopreservation and the causes of cryoinjury are reviewed. The
      possible roles of cryoprotectants and additives are considered in the context of
      their putative interactions with the sperm plasma membrane. Modern approaches to
      the laboratory assessment of spermatozoa after freeze-thawing are also briefly
      discussed.

PMID- 10924819
TI  - Storage of bovine semen in liquid and frozen state.
AB  - This review describes the historical and current methods used for storage of
      bovine semen. The essential physiological differences between liquid and frozen
      semen, their relative advantages and disadvantages are addressed, and the current
      state of technology, the procedures used, their merits and future possibilities
      are also discussed.

PMID- 10924820
TI  - Storage of buffalo (Bubalus bubalis) semen.
AB  - Characteristics of buffalo semen, diluents used for liquid storage, aspects
      involved in freezing and thawing of semen are reviewed, and fertility results
      after artificial insemination (AI) with frozen-thawed semen are given.

PMID- 10924821
TI  - Storage of ram semen.
AB  - Storage of ram semen in liquid and frozen state, the diluents used for both
      methods, processing, cooling, freezing and thawing of semen are reviewed. Factors
      influencing the fertility of stored semen and methods used for improvement are
      discussed, and fertility results of long-term frozen stored ram semen are also
      given.

PMID- 10924822
TI  - Production and storage of goat semen for artificial insemination.
AB  - Environmental influences on reproduction and semen production in the buck, the
      problem of interaction between seminal plasma and egg yolk or milk constituents
      in diluent, liquid storage and processing of semen for freezing are discussed. A
      review is given on the use of frozen-thawed semen for artificial insemination
      (AI) in spontaneous and induced oestrus and factors influencing the fertility.

PMID- 10924823
TI  - Storage of boar semen.
AB  - The problems, aspects and methods of liquid storage and freeze-thawing of boar
      semen are discussed and a review is given on examination of spermatozoa by the
      recent fluorescent staining methods.

PMID- 10924824
TI  - Reproductive aspects and storage of semen in camelidae.
AB  - The characteristics of male and female reproductive tracts and reproductive
      physiology in camelids are described. An account is given on methods of
      collection, characteristics and storage of semen, and fertility after artificial
      insemination (AI) with fresh, liquid-stored and frozen-thawed lamoid and camel
      semen.

PMID- 10924825
TI  - Storage of semen and artificial insemination in deer.
AB  - Methods of collection and freezing of semen of some deer species and aspects of
      controlled reproduction associated with the use of frozen-thawed semen by
      artificial insemination (AI) are discussed.

PMID- 10924826
TI  - Storage of poultry semen.
AB  - Methods of semen collection and artificial insemination (AI) in poultry,
      requirement for diluents, methods of liquid and frozen storage of avian semen and
      evaluation of spermatozoa after storage for fertilizing ability are reviewed.
      Frozen storage of semen from non-domestic birds is also briefly discussed.

PMID- 10924827
TI  - Hygienic aspects of storage and use of semen for artificial insemination.
AB  - The artificial insemination (AI) industry has developed over the last 50 years to
      the extent that it is used in almost every country in the world. One of the main
      factors contributing to its success is the confidence of the farmers that
      germplasm is not associated with pathogens, so that AI can be performed without
      risks. This has been achieved as a result of a considerable amount of research
      based on sound scientific data that has identified the major risk pathogens. A
      summary of these studies, given in this section, shows that despite the large
      number of agents that could be transmitted via the semen, there are cost
      effective means to prevent such hazards. One of the basic rules is that the males
      should be housed in strictly protected semen collection centres (SCCs). Such
      centres should be approved by the veterinary authorities based upon specific
      criteria, which include special housing and operating specifications. This also
      includes specific means of monitoring the health of individual males through
      regular clinical examinations, assessment of semen and testings for various
      diseases. Two new challenges can now be identified, one relevant to so-called
      emerging diseases the impact of which on the status of the semen donors should
      always be assessed, and the second, relates to endangered genetic resources which
      may become extinct without active conservation programmes. The experience gained
      by the AI industry over the last 50 years should help to solve those problems.
      Currently, the use of semen derived from approved SCCs warrants their disease
      free status.

PMID- 10924828
TI  - Effects of high density lipoprotein containing high or low beta-carotene
      concentrations on progesterone production and beta-carotene uptake and depletion
      by bovine luteal cells.
AB  - Luteal cells were isolated from mid-luteal heifer ovaries by collagenase
      digestion. Cells were cultured with DMEM/Ham's F12 medium in serum pre-treated
      plastic culture dishes for periods of up to 11 days. As beta-carotene is almost
      completely insoluble in all polar solvents, it was added to cultures in either
      dimethyl sulphoxide (DMSO), tetrahydrofuran (THF) or as high-density lipoprotein
      (HDL) containing high or low beta-carotene concentrations. Medium was replaced
      after 24 h, thereafter medium was changed every 48 h. Treatment of cells with
      DMSO alone or with beta-carotene (5 micromol/l) in DMSO both resulted in
      significant (P<0.01) stimulation of progesterone production. beta-Carotene (5
      micromol/l) in THF did not alter progesterone production but 50 micromol/l beta
      carotene in THF resulted in significant inhibition (P<0.02) of progesterone
      production on days 3 and 7. Cultures were also supplemented with bovine HDL
      preparations containing equal concentrations of cholesterol (25 microg/ml) but
      high or low beta-carotene (12.4 or 0.44 microg/mg of cholesterol). Both HDL
      preparations significantly stimulated progesterone production (P<0. 001) but the
      high beta-carotene HDL was significantly (P<0.02) more effective than the low
      beta-carotene HDL. However, when given together with bovine luteinizing hormone
      (bLH) or dibutyryl cAMP (dbcAMP), the high beta-carotene HDL stimulated
      progesterone production less than did the low HDL (P<0.01). Uptake and depletion
      of beta-carotene by luteal cells were also examined in culture. beta-Carotene
      supplementation increased luteal cell beta-carotene from an initial level of 373
      ng per 10(6) cells to 2030 ng per 10(6) cells by day 6. In contrast, the levels
      in control cells decreased to 14% of starting values during the same period.
      Cells treated with HDL containing high beta-carotene on day 1 or days 1 and 3
      were then incubated with or without bLH or dbcAMP for a further 2 days to
      investigate the effect of bLH and dbcAMP on depletion of beta-carotene by luteal
      cells. beta-Carotene depletion in the luteal cells was significantly higher
      (P<0.05) in LH- and dbcAMP-treated cells than in the control cells in both
      groups. These results indicate that the use of solvents such as DMSO or THF may
      have undesirable effects due to alteration of cell membrane permeability.
      Supplementation with bLH or dbcAMP may increase the metabolism of beta-carotene
      in luteal cells. bLH or dbcAMP together with high beta-carotene HDL may, when
      combined with the effect of increased beta-carotene metabolism, give less
      stimulation than with low beta-carotene HDL.

PMID- 10924829
TI  - Effect of freezing rate of ram spermatozoa on subsequent fertility in vivo and in
      vitro.
AB  - Ram spermatozoa are most susceptible to damage during freezing between the
      temperatures of -10 degrees C and -25 degrees C. The objectives of the present
      study were to examine how freezing rate through this critical temperature zone
      affected the fertility of spermatozoa as assessed in vivo and in vitro. Semen
      from six adult rams was frozen at two different rates ("fast": 5 degrees C/min
      from +5 to -25 degrees C; "slow": 0.5 degrees C/min from +5 to -25 degrees C). In
      Experiment 1, semen from the fast and slow treatments was used to fertilize ovine
      oocytes that had been matured in vitro. Semen from the fast treatment yielded a
      higher cleavage rate (57% vs. 26%; P<0.001) and more blastocysts per oocyte (28%
      vs. 13%, P<0. 001) than slow-frozen. No correlation was found between fertilizing
      ability and viability as assessed by fluorescent probes. Experiment 2 was
      designed to establish the conception rates following both cervical and
      intrauterine insemination of frozen-thawed semen from the same bank of semen as
      used in Experiment 1. Ewes were superovulated with FSH and inseminated by
      laparoscopy with frozen semen. A significant difference was found in the number
      of fertilized ova following embryo recovery (81.4% vs. 39.3%; P<0.001). In a
      further study, 119 mature cull ewes were inseminated following a 12-day
      synchronization treatment with frozen semen by either intrauterine (laparoscopic)
      or cervical insemination. Insemination with fast-frozen semen resulted in a
      significantly higher pregnancy rate (P<0.05) irrespective of method of
      insemination. The data show that freezing rate affects the proportion of
      spermatozoa that retain their fertilizing ability post-thawing. However, once
      fertilization has occurred, development to the blastocyst stage is independent of
      freezing rate.

PMID- 10924830
TI  - The effect of a zinc, cobalt and selenium soluble glass bolus on trace element
      status and semen quality of ram lambs.
AB  - Supplemental zinc and selenium were administered to ram lambs grazed on pastures
      that were not considered to be deficient in either element. The breeding season
      and polygamy of the ram mean that his requirements for semen production will be
      relatively large over a short breeding season and this may induce a localised
      deficiency of zinc and/or selenium, thus resulting in a decrease in semen quality
      and production.Thirty-three 8-month-old ram lambs were kept at grass and fed a
      supplement of barley and peas, with ad libitum access to grass silage when
      grazing became restricted. On day 0, the rams were allocated to two groups by
      restricted randomisation of live weight. One group each had a zinc, cobalt and
      selenium soluble glass bolus (Zincosel(R), Telsol) administered with the other
      group not receiving a bolus to act as a control. Blood samples were taken by
      jugular venipuncture at day 0 (prior to bolus administration) and at days 23, 44,
      65 and 86. Blood samples were analysed for zinc status (plasma zinc
      concentration) and selenium status (erythrocyte glutathione peroxidase activity).
      Semen was collected once a week between days 44 and 86, by diversion during a
      natural mount. Semen quality was assessed by ejaculate volume, spermatocrit,
      sperm concentration, abnormal morphology, motility, percentage live (negrosin
      eosin stain), membrane integrity (hypo-osmotic swelling test (HOS)) and seminal
      fluid glutathione peroxidase activity and zinc concentration. The bolused lambs
      had a significantly increased erythrocyte glutathione peroxidase activity
      (P<0.01) on all samplings after bolusing and had significant increases in
      motility, proportion of live sperm and proportion of intact membranes indicated
      by the HOS. The bolused ram lambs had an increased selenium status and apparent
      improvement in semen membrane quality.

PMID- 10924831
TI  - Progestagen synchronisation in the absence of a corpus luteum results in the
      ovulation of a persistent follicle in cyclic ewe lambs.
AB  - Progestagens are widely used to synchronise oestrous in sheep but the effects on
      follicular dynamics are not clear. We tested the hypothesis that when luteolysis
      occurs early during progestagen synchronisation prolonged growth of the ovulatory
      follicle will occur. Cyclic ewe lambs (40.0+/-0.3 kg) were divided into three
      groups: eight ewes (Long group) received a progestagen sponge (60 mg
      medroxyprogesterone acetate) from Days 5 to 19 after oestrous and eight ewes
      (Short group) received a progestagen sponge on Day 5 which was replaced on Day 10
      and again on Day 15, and removed on Day 19 after oestrous. On Days 6 and 7, ewes
      in both groups received prostaglandin. A third group (n=5, Control) did not
      receive any treatment. The growth and development of follicles > or =2 mm in
      diameter were characterised using daily transrectal ultrasonography. On Day 18,
      blood samples were collected every 12 min for 8 h from five ewes in the Long and
      Short groups. Data were analysed by ANOVA. The maximum diameter and age
      (emergence to ovulation) of the ovulatory follicle was greater (P<0.01) in ewes
      in the Long group (7. 4+/-0.2 mm and 12.1+/-0.6 days) than in ewes in the Short
      group (6. 3+/-0.2 mm and 5.1+/-0.5 days) and Control group (6.3+/-0.4 mm and 6.
      8+/-0.6 days). On Day 18 of the cycle, LH pulse frequency and oestradiol
      concentrations were greater (P<0.05) in ewes in the Long group (3.2+/-1.1 pulse
      per 8 h and 1.15+/-0.09 pg ml(-1)) than the Short group (0.8+/-0.4 pulses per 8 h
      and 0.54+/-0.08 pg ml(-1)). We suggest that the negative feedback efficacy of a
      long-term progestagen sponge decreased with time and led to an increase in LH
      pulse frequency and prolonged growth of the ovulatory follicle. We conclude that,
      in the absence of luteal progesterone, synchronisation with a single progestagen
      sponge for 14 days resulted in higher LH pulse frequency and ovulation of a
      persistent follicle with a larger maximum diameter, compared with controls.

PMID- 10924832
TI  - Age-related changes in plasma testosterone concentrations and genital organs
      content of bulk and trace elements in the male dromedary camel.
AB  - There is a paucity of information regarding the influence of plasma testosterone
      concentrations and inorganic cations secreted in the different seminal fractions
      on the spermatozoon activity throughout the reproductive life of the one-humped
      camels. To demonstrate these relationships, the genital organs of 12 prepubertal
      (<3 years), 9 peripubertal (3-<5 years), 16 mature (5-<15 years) and 15 aged
      (>/=15 years) camels were collected from the Buraidah slaughter house (Al-Qassim
      Province, Saudi Arabia) during two consecutive breeding seasons (November-April)
      over 2 years. Plasma testosterone concentrations (mean+/-S.E.) did not exceed 1.4
      ng/ml in prepubertal animals with a 3-4 fold increase in peripubertal (3.2+/-0.4
      ng/ml) and mature (4.8+/-0.6 ng/ml) camels followed by about 50% decrease (2.6+/
      0.3 ng/ml) in aged ones. These hormonal changes were correlated significantly
      with concentrations of certain elements in the testes (highest Na, Ca and Cu
      contents), epididymides (highest P and Fe contents), prostate (highest Zn
      content), and bulbo-urethral glands (highest K and Mg contents). The significance
      of some interrelationships among the different cations and their biological
      effects on sperm production and metabolic activity were discussed.

PMID- 10924833
TI  - Oviductal isthmic motility patterns as monitored by polyview in unrestrained sows
      around ovulation.
AB  - A method for monitoring oviductal isthmic motility in sows incorporating a
      computer programme (Polyview) was developed. This method was found to be reliable
      and easy for recording and analysing data. Isthmic motility patterns were
      monitored from 11 h prior to and up to 36 h after ovulation in 13 unrestrained
      multiparous sows during their second oestrus after weaning. The amplitudes and
      frequencies of phasic pressure fluctuations in relation to the hormonal profiles
      were also calculated. The isthmic motility patterns were regular before ovulation
      changing to wave patterns during the peri-ovulatory period and eventually to
      irregular patterns after ovulation. The amplitudes and frequencies of phasic
      pressure fluctuations were significantly higher (p<0.05) prior to and soon after
      ovulation than afterwards. Plasma oestradiol-17beta levels significantly (p<0.05)
      decreased before ovulation while plasma progesterone levels increased
      significantly (p<0.05) after ovulation. Despite a significant decrease in the
      plasma levels of oestradiol-17beta prior to ovulation, the amplitudes and
      frequencies of phasic pressure fluctuations remained high until shortly after
      ovulation. This could have been due to the endogenous levels of oestradiol-17beta
      bound to the nuclear oestradiol-17beta receptors that might still have been
      present in the isthmus. Conversely, the irregular isthmic motility patterns, the
      decline in the frequencies of phasic pressure fluctuations and amplitudes seen
      after ovulation may have been due to the rising plasma levels of progesterone.
      The amplitudes and frequencies of phasic pressure fluctuations were highest at
      the time when oestradiol-17beta levels were highest and when progesterone levels
      were low. It can be concluded that the changes in the isthmic motility patterns,
      amplitudes and frequencies of phasic pressure fluctuations in relation to the
      changes in the plasma levels of oestradiol-17beta and progesterone seen in the
      present study prior to and after ovulation indicate a possible role of the
      oviduct in regulating gamete transport.

PMID- 10924834
TI  - Postmenopausal hormone therapy and coronary heart disease: clinical implications
      of recent randomized trial results.

PMID- 10924836
TI  - Hormone replacement therapy and the skin.
AB  - Estrogens have a profound influence on skin. The hypoestrogenism occurring after
      the menopause leads to measured deterioration in the skin. Estrogen receptors
      have been identified in the skin and the concentration of these receptors varies
      in the different parts of the body. Estrogen improves skin in more than one way,
      the collagen content and quality is improved, skin thickness is increased, while
      vascularisation is enhanced. The extracellular matrix responsible for the tone
      and appearance of the skin is also improved. It is not just the skin that shows
      an improvement with estrogen therapy but also skin appendages, such as hair.
      Estrogens have been shown to increase the hair follicle life cycle. Skin aging is
      not totally estrogen dependent because the ravages of age and the external
      environment play very important roles. The effects of estrogen on skin need
      further elucidation and with the emergence of newer techniques it is now possible
      to study more clearly the changes occurring at the cellular level. Estrogen
      replacement reverses the deleterious effect of estrogen deprivation on the skin,
      which is thus yet another organ that benefits from hormone replacement therapy.

PMID- 10924837
TI  - Health perception by women who work in a medical environment.
AB  - A mail survey was sent to 1154 women working in a university hospital, to assess
      the perception of health and the uptake of prevention strategies in an optimal
      setting. A list of 13 diseases was submitted and the women were asked to list the
      five diseases they found to be the most important for a woman of their age.
      Breast cancer was ranked among the five most important diseases by 85% of the
      women and uterus cancer by 71.3%. Other diseases, which have a high occurrence
      and mortality, like myocardial infarction, colon- and lung cancer were only
      ranked by approximately 30% of them. A high uptake of medical follow-up was
      reported by the surveyed women; 89% of them had seen a general practitioner or a
      gynaecologist during the past 12 months. Among women aged 50 and over, 92% had
      had at least one mammography in the past. However, only 20% had ever had faecal
      occult blood testing. Even among women who benefit from superior conditions for
      medical follow-up, the awareness of some diseases is low. Campaigns to increase
      awareness should consider the prevalence of diseases, their mortality and
      morbidity and also their actual perception in the targeted population.

PMID- 10924838
TI  - Estrogen replacement therapy in patients with endometrial cancer: prescription
      attitude of Belgian gynecologists.
AB  - BACKGROUND: Endometrial cancer is estrogen dependent and has been considered as a
      contraindication for HRT. Some uncontrolled studies reported no increase in
      recurrence in women who received ERT after they had suffered early stage
      endometrium cancer and many opinion leaders have mandated that early uterus
      cancer should not be considered as an absolute contraindication to HRT. AIM: We
      conducted a survey evaluating the prescription attitude of Belgian gynecologists
      (n=1363) towards a case describing a patient who presents indication for ERT
      (climacteric symptoms and osteoporosis) and a past history of early stage
      endometrium cancer. RESULTS: We obtained a 32% response rate. Overall, the
      physicians prescribed treatment in 67% of the cases. There was no difference in
      the prescription attitude in relation to gender or age of the physicians. Among
      the physicians who prescribed HRT, 49% stated that they would prescribe estrogen
      only therapy (unopposed estrogens) and 27% would prescribe a combined estrogen
      progestin therapy. CONCLUSION: Two out of three gynecologists, in Belgium, would
      accept, at least theoretically, to prescribe HRT to a woman with a history of
      early stage endometrial cancer, no signs of recurrence and recognized indications
      for HRT.

PMID- 10924839
TI  - Psychometric validation of two Italian quality of life questionnaires in
      menopausal women.
AB  - OBJECTIVE: To establish the psychometric properties of the Italian version of two
      quality of life (QOL) questionnaires in menopausal women: the psychological
      general well being index (PGWBI) and the women's health questionnaire (WHQ).
      METHOD: These questionnaires were translated into Italian and then self
      administered to out-patient women a first time, 1 week later in stable women to
      assess reproducibility, and 3 months later to evaluate responsiveness over time.
      Baseline analyses included: factorial structure, multitrait analysis, internal
      consistency reliability, and clinical validity. RESULTS: Questionnaires were
      returned by 155 women (median age: 54 years, median duration of amenorrhoea: 56
      months, median Kupperman index 26). Principal component analysis (PCA) of the
      PGWBI showed an important general factor and then, after rotation, three factors.
      The PCA of the WHQ showed ten factors. Only five reproduced the dimensions
      postulated a priori quite well. The item convergent validity was confirmed for
      all items of the major dimension of the two questionnaires, and the item
      divergent validity, although acceptable, was less satisfying for the PGWBI than
      the WHQ. The internal reliability was good (Cronbach's alpha > or = 0.70) for the
      PGWBI and for nine scales out of ten for the WHQ. The six dimensions of the PGWBI
      and most of the dimensions of the WHQ were significantly correlated to the
      Kupperman index, indicating the clinical validity of the instruments. The
      responsiveness to change in clinical status at 3 months was better in the PGWBI
      than in the WHQ with moderate effect size (around 0.5). CONCLUSION: The Italian
      versions of the PGWBI and the WHQ are reliable and useful for HRT clinical trials
      but the dimensional scores must be calculated bearing in mind the limitations in
      the structure. Other studies are needed to improve the factorial stability of
      certain WHQ dimensions. For the Italian version of the PGWBI, the validation
      process is to be completed by studies of mixed populations suffering from other
      types of disease.

PMID- 10924840
TI  - Nocturia and health in women aged 40-64 years.
AB  - To analyse the relationship between nocturnal micturition and health in 40- to 64
      year-old women. A questionnaire study was carried out in 3669 randomly selected
      women (out of 6000 invited) in the County of Jamtland, Sweden. Questions were
      asked about the general health status of health, health development during the
      last 5 years, nocturnal micturition, parity, menstrual status, menopausal
      symptoms, hormone replacement therapy, cardiac diseases, diabetes and snoring.
      Poor health was reported by 10.4%. In 24.1% of the women health development had
      been unfavourable in the last 5 years. Poor health was reported by 4.7% of women
      without nocturnal micturition, and by 11.2, 20.1 and 39.0% (P<0.0001) of women
      with one, two, and three or more nocturnal voiding episodes, respectively. In a
      multiple logistic regression analysis significant independent correlates of
      health were: one versus no nocturnal micturitions (odds ratio [OR] 2.2;
      confidence interval [CI] 1.5-3.3), two versus none (OR 3.2; 1.9-5.3), and three
      or more versus none (OR 6.5; 3.5-11.9), spasmodic chest pain (OR 6.6; CI 3.0
      14.5), irregular heart beats (OR 3.0; CI 2.1-4.3), diabetes (OR 5.1; CI 2.8-9.4),
      leg oedema> or =6 days/month versus <6 days/month (OR 23; CI 1.6-3.3), snoring: <
      or =3 times/week versus never (OR 1.4; CI 1.0-2.0), snoring 4-7 times/week versus
      never (OR 1.6; CI 1.1-2.2), being<5 years after versus being before the menopause
      (OR 1.6; 95% CI 1.0-2.5), 5-9 years after versus before the menopause (OR 1.7; CI
      1.0-2.9), > or =10 years after versus before the menopause (OR 2.2; CI 1.3-3.7),
      diuretic treatment (OR 2.8; CI 1.7-4.6). The perceived state of health in 40- to
      64- year-old women is profoundly affected by nocturia, independently of heart
      diseases, diabetes, snoring, age and menopausal status.

PMID- 10924841
TI  - Reproductive history in relation to plasma hormone levels in healthy post
      menopausal women.
AB  - OBJECTIVES: We sought to examine the relationship between reproductive history
      and measures of selected gonadotrophins and steroid hormones among post
      menopausal women. Previous studies have suggested that there is a negative
      correlation between parity and post-menopausal serum estrogens, which may be a
      mechanism by which pregnancies protect women from the development of breast
      cancer. METHODS: We analyzed women who experienced a natural menopause within the
      Healthy Women Study cohort both 1 and 8 years after menopause. Lifetime
      reproductive history was obtained and blood was assayed for estrone, estradiol,
      androstenedione, testosterone, follicle stimulating hormone (FSH), and
      luteinizing hormone (LH) at 1 year post-menopause and for many of these steroid
      hormones at 8 years post-menopause. Also at 8 years post-menopause, a hip bone
      mineral density measure was obtained. RESULTS: Age at menopause related to a
      modest increase in estrone at 1 year but a decrease in estrone and estradiol at
      eight years. Adjustment for body mass index (BMI), oral contraceptive use,
      alcohol use, cigarette smoking, and education had little impact on these
      findings. There were no other internally consistent relationships between
      reproductive variables and steroid hormones or hip-bone mineral density.
      CONCLUSIONS: These observations do not support the hypothesis that parity acts to
      diminish endogenous levels of post-menopausal estrogens.

PMID- 10924842
TI  - Variable bone mass recovery in hyperthyroid bone disease after radioiodine
      therapy in postmenopausal patients.
AB  - OBJECTIVES: Long-term follow-up of postmenopausal hyperthyroid females after
      radioiodine therapy, since hyperthyroidism is known to cause impressive bone loss
      which may increase the risk of bone fractures. METHODS: Bone mineral density
      (BMD) and biochemical parameters of bone metabolism in hyperthyroid
      postmenopausal patients were investigated before and 2 years after radioiodine
      therapy and compared with euthyroid age-matched controls. RESULTS: At baseline,
      the incidence of low BMD with t-scores more than 2.5 S.D. below normal was
      significantly higher in hyperthyroid patients (54%) than in controls (20%,
      P<0.001). Regardless of initial BMD values, osteocalcin (OC) was also higher in
      all hyperthyroid patients (P<0.0001). After 2 years, all treated patients were
      euthyroid and OC levels were in the upper normal range. In hyperthyroid patients
      with initially low BMD, bone density values had increased significantly by +6.5%
      (P<0.008) as compared with baseline values. In contrast, hyperthyroid patients
      with initially normal BMD showed a further decrease in lumbar BMD values of -4.3%
      despite radioiodine treatment. BMD in euthyroid controls decreased by -6.5%
      within 2 years. CONCLUSIONS: We conclude that hyperthyroid postmenopausal
      patients with generally increased bone turnover may show individual differences
      in bone loss and BMD recovery after radioiodine treatment. The mechanisms for
      this variable manifestation of osteoporosis have still to be elucidated, since
      this has implications for prophylactic and therapeutic strategies in these
      elderly patients.

PMID- 10924843
TI  - Effects of hormone replacement therapy on postmenopausal uterine myoma.
AB  - OBJECTIVES: To evaluate the effects of sequential continuous hormone replacement
      therapy (HRT) on myoma size and on pulsatility index (PI) of uterine arteries and
      to verify the correlation between uterine artery flow impedance and the growth
      rate of myoma in women receiving HRT. METHODS: In a prospective 1-year study 60
      postmenopausal women were enrolled into three study-groups to receive continuous
      transdermal 17beta-oestradiol 0.05 mg/day plus nomegestrolo acetate 5 mg/day
      sequentially added: 20 patients (group A) unaffected by uterine myomas, 20
      patients (group B) with single asymptomatic myoma <3 cm/14 cm3, 20 patients
      (group C) with single asymptomatic myoma >3 cm/14 cm3. The changes in myoma
      volume and in PI were assessed by means of transvaginal ultrasonographic scan
      every 3 months. The patients with myoma were divided into two subgroups:
      quiescent myoma (B1, C1) and growing myoma (B2, C2). RESULTS: No significant
      increase of uterine fibroids volume was found after 1-year HRT (24.14+/-20.02-
      >28.81+/-30.02 cm3). Six out of eight myomas growing during HRT belonged to group
      C. The uterine artery basal PI value of group A was significantly higher (P<0.01)
      than the corresponding PI in group B and C. At 3 months follow-up, uterine artery
      PI was significantly higher (P<0.01) than the basal value in both group B (1.70+/
      0.22-->1.88+/-0.16) and C (1.59+/-0.28-->1.92+/-0.21). The baseline PI values in
      group B1 and C1 were significantly higher than the baseline values observed in
      group B2 and C2 (1.76+/-0.17 vs. 1.32+/-0.02, 1.76+/-0.16 vs. 1.24+/-0.08) and
      significantly lower than those observed in group A (2.39+/-0.47). After 3 months
      of HRT, the PI values were not significantly higher than the baseline values in
      groups B1 and C2 (1.76+/-0.17-->1.90+/-0.17; 1.24+/-0.08-->1.74+/-0.16), while
      they were significantly higher in group C1 (1.76+/-0.16-->2.01+/-0.17).
      CONCLUSIONS: Sequential continuous HRT does not increase the volume of the
      uterine myoma. The findings of very low resistance index in the uterine arteries
      of women with growing myoma may indicate the risk of growth of the neoplasia
      during HRT. The assessment of PI in the uterine arteries could be helpful in
      predicting the growth rate of the myomas before starting HRT.

PMID- 10924844
TI  - Antiestrogenic tamoxifen and toremifene increase serum leptin levels in
      postmenopausal breast cancer patients.
AB  - OBJECTIVES: Because estrogens stimulate the synthesis and release of leptin in
      the adipocytes, the effect of antiestrogens on the circulating leptin levels were
      studied. METHODS: Thirty postmenopausal patients with breast cancer were
      randomized to start either with tamoxifen (20 mg/day, n=15) or toremifene (40
      mg/day, n=15), and the patients were examined and serum leptin concentrations
      measured before the study and at 6 and 12 months. RESULTS: The baseline leptin
      concentrations ranged from 4.4 to 60.0 microg/l (15.3+/-13.1 microg/l, mean+/
      S.D.), and it correlated positively with the body mass index (BMI) of the
      subjects (r=0.73, P=0.0001). Taking as a whole the antiestrogen regimen was
      associated with elevated leptin levels at 6 months (19.5+/-13.8 microg/l,
      P=0.0001) but no excess increase in leptin levels were seen at 12 months (20.9+/
      13.5 microg/l, NS). Subgroup analysis showed no difference between the effects of
      tamoxifen or toremifene on leptin. BMI increased in 21 women (from 26.2+/-4.3 to
      27.3+/-4.8 kg/m2, P=0.0001) at 6 months, but not after that; in nine women BMI
      did not change. There was no significant correlation between the change in leptin
      levels and the change in BMI in either group implying that antiestrogens may
      specifically stimulate leptin production. CONCLUSIONS: Antiestrogens may
      stimulate the synthesis and release of leptin in the adipocytes. This effect of
      antiestrogens resembles the effect of estrogen and consequently stimulation of
      leptin production can be added to the estrogenic effects of antiestrogens.

PMID- 10924845
TI  - Analysis of 11-nor-9-carboxy-delta(9)-tetrahydrocannabinol in biological samples
      by gas chromatography tandem mass spectrometry (GC/MS-MS).
AB  - Gas chromatography tandem mass spectrometry (GC/MS-MS) analysis of 11-nor-carboxy
      delta(9)-tetrahydrocannabinol (delta(9)-THC-COOH), the major metabolite of
      delta(9)-tetrahydrocannabinol, in biological samples is reported. The proposed
      method, using deuterated delta(9)-THC-COOH as an internal standard, is able to
      detect the major metabolite of cannabis derivatives at very low levels
      (picograms/millilitre) with high specificity. These characteristics render the
      proposed analytical procedure suitable for confirmatory analysis in drug testing
      for cannabis use.

PMID- 10924846
TI  - Genetic differentiation within and between four UK ethnic groups.
AB  - In previous papers [L.A. Foreman, J.A. Lambert, I.W. Evett, Regional genetic
      variation in Caucasians, Forensic Sci. Int. 95 (1998) 27-37; L.A. Foreman,
      Analyses to investigate appropriate measures of differentiation between European
      Caucasian populations using short tandem repeat (STR) data, FSS Research Report
      FSS-RR-804 (1999)], we have carried out detailed investigations of the level of
      regional and national variation in STR characteristics exhibited within white
      Caucasian populations. The studies described here extend our earlier work to the
      black African/Caribbean and Asian (Indo-Pakistani) populations of the UK,
      routinely considered in casework calculations at the Forensic Science Service
      (FSS). In addition, estimation of allele distributions and database comparisons
      are carried out for two further populations, i.e. those classified as containing
      individuals of Oriental and Arabic appearance.

PMID- 10924847
TI  - The 1998-1999 collaborative exercises and proficiency testing program on DNA
      typing of the Spanish and Portuguese Working Group of the International Society
      for Forensic Genetics (GEP-ISFG).
AB  - A total of 28 laboratories (labs) submitted results for the 1998 collaborative
      exercise and the proficiency testing program of the Spanish and Portuguese
      Working Group of the International Society for Forensic Genetics (GEP-ISFG)
      group. This number increased to 46 labs in 1999. Six bloodstains were submitted,
      each one with 200 microl soaked in cotton except the sample no. 6 submitted for
      DNA quantification which had 2 microl. One of the samples was a mixed stain. A
      paternity testing case and a criminal case in the 1998 trial (GEP'98) and two
      paternity testing cases in 1999 (GEP'99) were included and the statistical
      evaluation of the evidence was requested in both cases. In the GEP'99 trial, a
      theoretical paternity testing case was included. A total of 52 DNA genetic
      markers were used by the participants in the GEP'98 trial, which increased to 101
      in GEP'99. Despite this increasing number of participating labs, results remained
      quite satisfactory. All the labs used PCR-based DNA polymorphisms with an
      increasing number of markers, obtaining good results. SLPs were used by a
      decreasing number of labs but the results indicated a good level of expertise
      despite the different protocols used. Good results were also obtained for mtDNA
      despite the difficulties presented by the samples due to the presence of length
      heteroplasmy in some samples in both trials. The detection of heteroplasmy
      should, however, be improved. Similar conclusions were reached for both, the
      paternity and the criminal case by all the labs. Common methodologies for the
      statistical evaluation of the paternity case were used and the paternity index
      and the probability of paternity (with an a priori value of 0.5) reported by most
      of the labs. Also, a great uniformity was found in the evaluation of the criminal
      case despite the lack of a specific hypothesis in the design of the exercise.
      Some errors in statistical programs or in calculations were detected in a
      theoretical paternity case included in the GEP'99 trial for statistical analysis.

PMID- 10924848
TI  - A new method for the evaluation of matches in non-recombining genomes:
      application to Y-chromosomal short tandem repeat (STR) haplotypes in European
      males.
AB  - A 9-locus microsatellite framework (minimal haplotype), previously developed for
      forensic purposes so as to facilitate stain analysis, personal identification and
      kinship testing, has been adopted for the establishment of a large reference
      database of male European Y-chromosomal haplotypes. The extent of population
      stratification pertaining to this database, an issue crucial for its practical
      forensic application, was assessed through analysis of molecular variance (AMOVA)
      of the 20 regional samples included. Despite the notion of some significant
      haplotype frequency differences, which were found to correlate with known
      demographic and historic features of Europeans, AMOVA generally revealed a high
      level of genetic homogeneity among the populations analyzed. Owing to their high
      diversity, however, accurate frequency estimation is difficult for Y-STR
      haplotypes when realistic (i.e. moderately sized) datasets are being used. As
      expected, strong pair-wise and higher order allelic associations were found to
      exist between all markers studied, implying that haplotype frequencies cannot be
      estimated as products of allele frequencies. A new extrapolation method was
      therefore developed which treats haplotype frequencies as random variables and
      generates estimates of the underlying distribution functions on the basis of
      closely related haplotypes. This approach, termed frequency 'surveying', is based
      upon standard population genetics theory and can in principle be applied to any
      combination of markers located on the Y-chromosome or in the mitochondrial
      genome. Application of the method to the quality assured reference Y-STR
      haplotype database described herein will prove very useful for the evaluation of
      positive trace-donor matches in forensic casework.

PMID- 10924849
TI  - Corrigendum to "Screening postmortem blood and tissues for nine classes of drugs
      of abuse using automated microplate immunoassay"

PMID- 10924850
TI  - Signal transduction by oxidants: look who's talking.

PMID- 10924851
TI  - Recent advances towards understanding redox mechanisms in the activation of
      nuclear factor kappaB.
AB  - The transcription factor, nuclear factor-kappaB (NF-kappaB) has been studied
      extensively due to its prominent role in the regulation of immune and
      inflammatory genes, apoptosis, and cell proliferation. It has been known for more
      that a decade that NF-kappaB is a redox-sensitive transcription factor. The
      contribution of redox regulation and the location of potential redox-sensitive
      sites within the NF-kappaB activation pathway are subject to intense debate due
      to many conflicting reports. Redox regulation of NF-kappaB has been extensively
      addressed in this journal and the reader is referred to two comprehensive reviews
      on the subject [1,2]. With the identification of signaling intermediates proximal
      to the degradation of the inhibitor, IkappaB, the number of potential redox
      sensitive sites is rapidly increasing. The purpose of this review is to address
      recent insights into the NF-kappaB signaling cascades that are triggered by
      proinflammatory cytokines such as TNF-alpha and IL-1beta. In addition, the role
      of nitrogen monoxide (.NO) in the regulation of NF-kappaB will be reviewed.
      Opportunities for redox regulation that occur upstream of IkappaB-alpha
      degradation, as well as the potential for redox control of phosphorylation of NF
      kappaB subunits, will be discussed. Redox-sensitive steps are likely to depend on
      the nature of the NF-kappaB activator, the type of reactive oxygen or nitrogen
      species involved, the selectivity of signaling pathways activated, as well as the
      cell type under investigation. Lastly, it is discussed how redox regulation of NF
      kappaB activation is likely to involve multiple subcellular compartments.

PMID- 10924852
TI  - The JNK and P38 MAP kinase signaling pathways in T cell-mediated immune
      responses.
AB  - The mitogen-activated protein (MAP) kinase family members, which include the
      extracellular response kinases (ERK), p38, and c-Jun amino terminal kinases
      (JNK), play a role in mediating signals triggered by cytokines, growth factors,
      and environmental stress. JNK and p38 MAP kinases have been involved in
      inflammatory processes induced by a variety of stimuli, such as oxidative stress.
      Here, we describe the role of the JNK and p38 MAP kinase signaling pathways in
      the development of T cells in the thymus, and activation and differentiation of T
      cells in the peripheral immune system.

PMID- 10924853
TI  - Activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-dependent
      transcriptional events in carcinogenesis.
AB  - Generation of reactive oxygen species (ROS) during metabolic conversion of
      molecular oxygen imposes a constant threat to aerobic organisms. Other than the
      cytotoxic effects, many ROS and oxidants are also potent tumor promoters linking
      oxidative stress to carcinogenesis. Clonal variants of mouse epidermal JB6 cells
      originally identified for their differential susceptibility to tumor promoters
      also show differential reduction-oxidation (redox) responses providing a unique
      model to study oxidative events in tumor promotion. AP-1 and NF-kappaB, inducible
      by tumor promoters or oxidative stimuli, show differential protein levels or
      activation in response to tumor promoters in JB6 cells. We further demonstrated
      that AP-1 and NF-kappaB are both required for maintaining the transformed
      phenotypes where inhibition of either activity suppresses transformation response
      in JB6 cells as well as human keratinocytes and transgenic mouse. NF-kappaB
      proteins or extracellular signal-regulated kinase (ERK) but not AP-1 proteins are
      shown to be sufficient for conversion from transformation-resistant to
      transformation-susceptible phenotype. Insofar as oxidative events regulate AP-1
      and NF-kappaB transactivation, these oxidative events can be important molecular
      targets for cancer prevention.

PMID- 10924854
TI  - Protein kinase C signaling and oxidative stress.
AB  - Oxidative stress is involved in the pathogenesis of various degenerative diseases
      including cancer. It is now recognized that low levels of oxidants can modify
      cell-signaling proteins and that these modifications have functional
      consequences. Identifying the target proteins for redox modification is key to
      understanding how oxidants mediate pathological processes such as tumor
      promotion. These proteins are also likely to be important targets for
      chemopreventive antioxidants, which are known to block signaling induced by
      oxidants and to induce their own actions. Various antioxidant preventive agents
      also inhibit PKC-dependent cellular responses. Therefore, PKC is a logical
      candidate for redox modification by oxidants and antioxidants that may in part
      determine their cancer-promoting and anticancer activities, respectively. PKCs
      contain unique structural features that are susceptible to oxidative
      modification. The N-terminal regulatory domain contains zinc-binding, cysteine
      rich motifs that are readily oxidized by peroxide. When oxidized, the
      autoinhibitory function of the regulatory domain is compromised and,
      consequently, cellular PKC activity is stimulated. The C-terminal catalytic
      domain contains several reactive cysteines that are targets for various
      chemopreventive antioxidants such as selenocompounds, polyphenolic agents such as
      curcumin, and vitamin E analogues. Modification of these cysteines decreases
      cellular PKC activity. Thus the two domains of PKC respond differently to two
      different type of agents: oxidants selectively react with the regulatory domain,
      stimulate cellular PKC, and signal for tumor promotion and cell growth. In
      contrast, antioxidant chemopreventive agents react with the catalytic domain,
      inhibit cellular PKC activity, and thus interfere with the action of tumor
      promoters.

PMID- 10924855
TI  - Calcium signaling and oxidant stress in the vasculature.
AB  - Recent evidence suggests that oxidant stress plays a major role in several
      aspects of vascular biology. Oxygen free radicals are implicated as important
      factors in signaling mechanisms leading to vascular pathologies such as
      postischemic reperfusion injury and atherosclerosis. The role of intracellular
      Ca(2+) in these signaling events is an emerging area of vascular research that is
      providing insights into the mechanisms mediating these complex physiological
      processes. This review explores sources of free radicals in the vasculature, as
      well as effects of free radicals on Ca(2+) signaling in vascular endothelial and
      smooth muscle cells. In the endothelium, superoxides enhance and peroxides
      attenuate agonist-stimulated Ca(2+) responses, suggesting differential signaling
      mechanisms depending on radical species. In smooth muscle cells, both superoxides
      and peroxides disrupt the sarcoplasmic reticulum Ca(2+)-ATPase, leading to both
      short- and long-term effects on smooth muscle Ca(2+) handling. Because vascular
      Ca(2+) signaling is altered by oxidant stress in ischemia-related disease states,
      understanding these pathways may lead to new strategies for preventing or
      treating arterial disease.

PMID- 10924856
TI  - Lipid oxidation products in cell signaling.
AB  - The recent research on the impact that oxidative changes of biolipids could have
      in pathophysiology serves to explain how free radical-driven reactions not only
      are considered as mere toxicologic events, but also modulators of cell activity
      and function. Oxidatively modified low-density lipoproteins are known to affect
      various cellular processes by modulating various molecular pathways and signaling
      nuclear transcription. Among the lipid oxidation products detectable in ox-LDLs,
      and also in the atherosclerotic plaques, 4-hydroxynonenal has been widely
      investigated. This aldehyde was shown to upregulate AP-1 transcription factor,
      signaling through the MAP kinase pathway, with eventual nuclear localization and
      induction of a series of genes. Further, oxidation products of cholesterol and
      cholesterol esters, in ox-LDL are of similar interest, especially in relation to
      the pathogenesis of fibrosclerotic lesions of the arterial wall.

PMID- 10924857
TI  - Intercellular adhesion molecule-1 (ICAM-1) expression and cell signaling
      cascades.
AB  - The collective interaction between cells is, in part, mediated by different
      families of adhesion molecules. Intercellular adhesion molecules (ICAMs) are
      structurally related members of the immunoglobulin supergene family and are
      ligands for the beta2 integrin molecules present on leukocytes. Of the five ICAMs
      identified, ICAM-1 is the most extensively studied. Although ICAM-1 is expressed
      constitutively at low levels on endothelial cells and on some lymphocytes and
      monocytes, its expression can be significantly increased in the presence of
      cytokines (TNFalpha, IL-1, IFNgamma) and reactive oxygen species. Depending upon
      cell type, ICAM-1 participates in trafficking of inflammatory cells, in cell:cell
      interactions during antigen presentation, in microbial pathogenesis, and in
      signal transduction through outside-in signaling events. Again, depending upon
      cell type examined, ICAM-1 engagement has been documented to activate specific
      kinases through phosphorylation, resulting in transcription factor activation and
      increased cytokine production, increased cell membrane protein expression,
      reactive oxygen species production, and cell proliferation.

PMID- 10924858
TI  - Oxidative stress and cell cycle checkpoint function.
AB  - Oxidative stress and the damage that results from it have been implicated in a
      wide number of disease processes including atherosclerosis, autoimmune disorders,
      neuronal degeneration, and cancer. Reactive oxygen species (ROS) are ubiquitous
      and occur naturally in all aerobic species, coming from both exogenous and
      endogenous sources. ROS are quite reactive and readily damage biological
      molecules, including DNA. While the damaging effects of ROS on DNA have been
      intensively studied, the effects of oxidative damage on cell cycle checkpoint
      function have not. Here will we review several biologically important ROS and
      their sources, the cell cycle, checkpoints, and current knowledge about the
      effects of ROS on initiating checkpoint responses.

PMID- 10924859
TI  - Regulation of redox glutathione levels and gene transcription in lung
      inflammation: therapeutic approaches.
AB  - Glutathione (L-gamma-glutamyl-L-cysteinylglycine, GSH), is a vital intra- and
      extracellular protective antioxidant. Glutathione is synthesized from its
      constituent amino acids by the sequential action of gamma-glutamylcysteine
      synthetase (gamma-GCS) and GSH synthetase. The rate-limiting enzyme in GSH
      synthesis is gamma-GCS. Gamma-GCS expression is modulated by oxidants, phenolic
      antioxidants, and inflammatory and anti-inflammatory agents in various mammalian
      cells. The intracellular GSH redox homeostasis is strictly regulated to govern
      cell metabolism and protect cells against oxidative stress. Growing evidence has
      suggested that cellular oxidative processes have a fundamental role in
      inflammation through the activation of stress kinases (JNK, MAPK, p38) and redox
      sensitive transcription factors such as NF-kappaB and AP-1, which differentially
      regulate the genes for proinflammatory mediators and protective antioxidant genes
      such as gamma-GCS, Mn-SOD, and heme oxygenase-1. The critical balance between the
      induction of proinflammatory mediators and antioxidant genes and the regulation
      of the levels of GSH in response to oxidative stress at the site of inflammation
      is not known. Knowledge of the mechanisms of redox GSH regulation and gene
      transcription in inflammation could lead to the development of novel therapies
      based on the pharmacological manipulation of the production of this important
      antioxidant in inflammation and injury. This FORUM article features the role of
      GSH levels in the regulation of transcription factors, whose activation and DNA
      binding leads to proinflammatory and antioxidant gene transcription. The
      potential role of thiol antioxidants as a therapeutic approach in inflammatory
      lung diseases is also discussed.

PMID- 10924860
TI  - How does ascorbic acid prevent endothelial dysfunction?
AB  - Human coronary and peripheral arteries show endothelial dysfunction in a variety
      of conditions, including atherosclerosis, hypercholesterolemia, smoking, and
      hypertension. This dysfunction manifests as a loss of endothelium-dependent
      vasodilation to acetylcholine infusion or sheer stress, and is typically
      associated with decreased generation of nitric oxide (NO) by the endothelium.
      Vitamin C, or ascorbic acid, when acutely infused or chronically ingested,
      improves the defective endothelium-dependent vasodilation present in these
      clinical conditions. The mechanism of the ascorbic acid effect is unknown,
      although it has been attributed to an antioxidant function of the vitamin to
      enhance the synthesis or prevent the breakdown of NO. In this review, multiple
      mechanisms are considered that might account for the ability of ascorbate to
      preserve NO. These include ascorbate-induced decreases in low-density lipoprotein
      (LDL) oxidation, scavenging of intracellular superoxide, release of NO from
      circulating or tissue S-nitrosothiols, direct reduction of nitrite to NO, and
      activation of either endothelial NO synthase or smooth muscle guanylate cyclase.
      The ability of ascorbic acid supplements to enhance defective endothelial
      function in human diseases provides a rationale for use of such supplements in
      these conditions. However, it is first necessary to determine which of the many
      plausible mechanisms account for the effect, and to ensure that undesirable toxic
      effects are not present.

PMID- 10924861
TI  - Biphasic effect of UVA radiation on STAT1 activity and tyrosine phosphorylation
      in cultured human keratinocytes.
AB  - The effect of ultraviolet A (UVA) radiation on the DNA-binding activity of the
      transcription factor STAT1 was studied by electromobility shift assay in the
      human keratinocyte cell line NCTC 2544. The STAT1-binding activity exhibited a
      biphasic pattern as a function of UVA doses. For UVA doses lower than 0.6
      J/cm(2), a dose-dependent increase in STAT1 activity was observed. In a second
      phase, with higher UVA doses (1.5 to 9 J/cm(2)), the activity decreased and
      reached control value at 6 J/cm2. The enhancement of STAT1 activity was
      transient, peaked at 1 h after UV irradiation, and regularly decreased to control
      value 24 h after UV. Genistein, a tyrosine kinase inhibitor, H7, a
      serine/threonine kinase inhibitor, and PD 98059, a MEK inhibitor, prevented the
      UVA-induced enhancement of STAT1-binding activity, suggesting the involvement of
      Tyr, Ser/Thr kinases, and MEK in the observed effect. Immunoblot analysis
      directly demonstrated that the amount of Tyr-phosphorylated STAT1 was parallel to
      its DNA-binding activity. Immunoblot analysis also demonstrated the nuclear
      transport of STAT1 after UVA irradiation at low doses. At high doses, a decrease
      in the STAT1 level was observed both in the cytoplasmic and the nuclear
      compartments, suggesting that the inactivation was due to a degradation process.
      UVA irradiation initiated a dose-dependent increase in lipid peroxidation
      products and reactive oxygen species. Furthermore, the involvement of the
      oxidative stress in the UVA-induced effect on STAT1 activity is suggested by the
      protective action of the antioxidants alpha-tocopherol and N-acetylcysteine on
      both the activation phase (UVA doses lower than 1.5 J/cm(2)) and the inhibitory
      phase. By contrast, the pro-oxidant drug buthionine sulfoximine enhanced the
      effect of UVA on STAT1-binding activity. Since STATs are known as transducers of
      cytokine action, the enhancement of STAT1 activity by low doses of UVA might be
      related to the proinflammatory effect of solar radiations at the skin level.

PMID- 10924862
TI  - Measurement of cellular repair activities for oxidative DNA damage.
AB  - Two related assays capable of determining cell extract repair activities for
      different oxidative lesions in DNA are described. Both assays measure the
      incorporation of radiolabeled nucleotides during repair of an oxidatively damaged
      template in a cell-free system. The assays differ in the type of oxidative damage
      present in the DNA. In one, singlet oxygen is used to generate predominantly 8
      oxo-2'-deoxyguanosine lesions. In the other, hydroxyl radicals are used to
      generate a broad spectrum of damage including oxidized bases and strand breaks.
      Assay conditions were adjusted to ensure that radiolabel incorporation was
      directly proportional to cell extract repair activity. These assays represent
      sensitive tools for investigating the regulation of repair systems for oxidative
      DNA damage.

PMID- 10924864
TI  - Ultrastructural identification of dentate granule cell death from pilocarpine
      induced seizures.
AB  - Cell loss in the hippocampal formation is a common event in patients with
      temporal lobe epilepsy. The belief that dentate granule neurons are relatively
      resistant to excitotoxic injury has recently been challenged both, in epileptic
      patients and in animal models of temporal lobe epilepsy. The nature of dentate
      granule cell damage in epilepsy has been reported as either apoptotic, necrotic
      or both. The lack of a consensus on this topic stems from use of different animal
      models and different experimental techniques for characterizing the
      apoptotic/necrotic process. Using electron microscopy for defining the, nature of
      cell loss and one of the main animal models of status epilepticus (SE) we have
      focussed on the nature of the degenerative process in dentate granule cells.
      Ultrastructural morphological changes of these cells were evaluated 2.5-48 h
      after pilocarpine-induced status epilepticus. A variety of morphologies ranging
      from apoptosis to necrosis, could be seen at 2.5 h after SE onset and continued
      at least over the following 48 h. Some cells displayed coalescence of chromatin
      against nuclear membranes. In such cases however, chromatin did not have well
      defined edges (as it should, if it were apoptosis). Condensation of cytoplasm.
      present in both processes was also frequently found. Neither obvious apoptotic
      budding-off of cytoplasm nor typical membrane-bound apoptotic bodies were found.
      Our results indicate that in the dentate granule cell layer pilocarpine-induced
      SE promotes a degenerative process in which apoptotic and necrotic features
      overlap.

PMID- 10924863
TI  - The effects on lipid and apolipoprotein serum levels of long-term carbamazepine,
      valproic acid and phenobarbital therapy in children with epilepsy.
AB  - The aim of the present study was to assess the effect of long-term carbamazepine
      (CBZ), valproic acid (VPA) and phenobarbital (PB) treatment on serum lipids and
      apolipoproteins in epileptic children. Serum levels of total cholesterol (TC),
      high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol
      (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglycerides
      (TGs) were measured and the LDL-C/HDL-C and TC/HDL-C ratios were calculated in
      320 children and adolescents (129 receiving CBZ, 127 receiving VPA and 64
      receiving PB) suffering from various types of epilepsy. Additionally, in a
      subgroup of 181 children (68 CBZ; 78 VPA; 35 PB) apolipoprotein A-I (apoA-I),
      apolipoprotein B (apoB), HDL2-C and HDL3-C were measured and apoA-I/apoB and HDL2
      C/HDL3-C ratios were calculated. Results of the measurements were compared with
      those of 169 age-and sex-matched healthy controls. None of the variables
      considered was significantly correlated with time elapsed since start of
      treatment or with drug concentration in serum. TC and LDL-C serum levels were
      high in children receiving CBZ or PB and low in those treated with VPA. Serum LDL
      C level exceeded 130 mg/dl in 27.9% of CBZ-group, 31.8% of the subjects receiving
      PB, but only in 7% of those receiving VPA and in 11.8% of control group subjects.
      CBZ-treated children also showed high HDL-C and HDL3-C values. In the group
      receiving VPA, HDL2-C, HDL2-C/HDL3-C ratio and apo B were significantly lower
      than in the control group. Mean apoA-I levels were low in all treated groups: by
      contrast, in neither group did TGs, VLDL-C levels and TC/HDL-C or LDL-C/HDL-C
      ratios differ significantly from the corresponding control group. Our results
      suggest that the effects of long-term AED therapy on lipid profile and,
      particularly, on apolipoprotein serum levels increase risk of atherosclerosis
      related disease. Moreover, these results confirm our previously reported
      increased risk in CBZ and PB-treated patients.

PMID- 10924865
TI  - Total percentage body weight changes during add-on therapy with tiagabine,
      carbamazepine and phenytoin.
AB  - Changes in body weight were evaluated in 349 patients from a study comparing
      efficacy of add-on therapy with tiagabine (TGB), carbamazepine (CBZ) or phenytoin
      (PHT). TGB add-on therapy showed no significant weight changes when added to
      either PHT or CBZ. CBZ add-on therapy showed a significant percentage weight gain
      of a mean body increase of 1.5% (P = 0.002). Adjunctive TGB therapy had no
      significant effect on total body weight, while adjunctive CBZ therapy was
      associated with weight gain.

PMID- 10924866
TI  - Comparison between the QOLIE-31 and derived QOLIE-10 in a clinical trial of
      levetiracetam.
AB  - PURPOSE: to determine whether the QOLIE-10, an abbreviated quality of life
      questionnaire, provides results similar to the more detailed QOLIE-31 instrument
      when the ten items are derived from the QOLIE-31. METHODS: the QOLIE-31 was
      completed by 246 patients participating in UCB protocol N132 at baseline and
      after 18 weeks of treatment with levetiracetam (LEV 1000 or 3000 mg) or placebo
      added to standard therapy. QOLIE-10 components and total scores were calculated
      from the QOLIE-31 data. RESULTS: baseline QOLIE-10 components and total score
      correlated highly with corresponding QOLIE-31 scores, both at baseline and follow
      up (range 0.70-0.95). Changes from baseline to follow-up were significantly
      different (ANCOVA) among treatment groups for both the QOLIE-10 and QOLIE-31 for
      the total score (P = 0.02, P = 0.009, respectively), seizure worry (P = 0.005, P
      = 0.0003) and cognitive functioning (P = 0.01, P = 0.01). One subscale (overall
      QOL) showed significant change with the QOLIE-31 (P = 0.04), but not with the
      QOLIE-10 (P = 0.07). Differences in QOLIE-10 scores were found between responders
      (> or = 50% partial onset seizure reduction) and non-responders for the total
      score (P = 0.0001) and two components (overall QOL P = 0.002, social function P =
      0.0003). In the QOLIE-31, the total score and six subscale scores (all except
      medication effects) were significantly different. Both instruments were able to
      detect change over time. Responsiveness assessed by effect sizes (- 0.1 for non
      responders, 0.4 for responders, 0.8 for seizure-free patients) and the Guyatt
      statistic (0.1, 0.6 and 1.0, respectively) was similar for both instruments.
      CONCLUSIONS: although the QOLIE-10 was designed as a screening tool, it can be
      scored and used in research. The total score did discern differences among
      treatments in a clinical trial. Nonetheless, questionnaires with multiple, multi
      item subscales provide more detailed information than abbreviated forms. The
      QOLIE-31 is preferred where time and resources are available.

PMID- 10924867
TI  - The impact of epilepsy from the patient's perspective I. Descriptions and
      subjective perceptions.
AB  - This study surveyed the perceptions about and subjective experience of 1023
      people with epilepsy in two community-based samples: one from a national postal
      survey; the other callers to the Epilepsy Foundation. Response to a mail survey
      was 49%. In comparison with US Census Bureau norms, respondents had received less
      education, were less likely to be employed or married, and came from lower income
      households. Complex partial seizures were the most prevalent seizure type, but a
      convulsion had occurred in 61%. Fifty percent of respondents reported incomplete
      control of their seizure disorder, although 25% of these had a seizure in the
      prior year. Thirteen percent had a longest inter-seizure interval of a year or
      greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day.
      Respondents listed uncertainty and fear of having a seizure as the worst thing
      about having epilepsy. Lifestyle, school, driving, and employment limits were
      also listed as major problems. When asked to rank a list of potential problems,
      cognitive impairment was ranked highest. These data indicate that ongoing medical
      and psychosocial problems continue for those with epilepsy in the view of those
      questioned and their families, even in a sample where the majority report good
      control of their epilepsy.

PMID- 10924868
TI  - The impact of epilepsy from the patient's perspective II: views about therapy and
      health care.
AB  - A national survey of 1023 people with epilepsy in the US assessed their attitudes
      about their therapies. Subjects were drawn from responders to a previous national
      survey of US households or from those who phoned the Epilepsy Foundation. Overall
      response rate was 49%. Approximately 90% of the respondents were taking
      medications for their epilepsy. Only 56% were on monotherapy, while 26% were
      taking two, 6% three, and 2% four medications. Only 68% of respondents were very
      satisfied with their current seizure medications. When asked to rank five areas
      of importance regarding their seizure medication, the rank order (highest to
      lowest) was seizure control, fewer side effects, convenient dosing regimens and
      cost. Adverse medication events were listed in descending rank order as problems
      with cognition, energy level, school performance, childbearing, coordination, and
      sexual function. Inter-individual differences in side effects of concern were
      listed, suggesting medication choices should be individualized according to
      potential side effects. Twenty percent of 920 respondents adjusted their
      medications on their own, by adjusting amount (62%), dosing schedule (31%), or
      both (3%). Eighty percent of respondents were satisfied with their medical care
      systems. In this group, 82% had health insurance that covered epilepsy. The large
      majority (94%) of respondents had seen a neurologist. Subjects expressed
      dissatisfaction about time limits and lack of accessible information about
      epilepsy. People with epilepsy are generally satisfied with efforts to treat
      their disorder, but adverse events are of concern. Many patients requested more
      information about epilepsy.

PMID- 10924869
TI  - Patterns of cerebellar atrophy in patients with chronic epilepsy: a quantitative
      neuropathological study.
AB  - Cerebellar atrophy occurring in patients with chronic epilepsy is considered
      either to be a sequel of cumulative seizure-mediated cell loss or a side effect
      of phenytoin treatment but there is little neuropathological data regarding the
      distribution of this cerebellar damage. We aimed to address if there is any
      relationship between the localisation of the cortical pathology in symptomatic
      epilepsy and the pattern of neocerebellar atrophy. A quantitative
      neuropathological post mortem analysis of the lobular distribution of hemispheric
      cerebellar atrophy in 16 patients with chronic epilepsy and four controls was
      carried out. Cerebellar atrophy, as measured by significant reductions in
      hemispheric linear Purkinje cell densities was confirmed in the epilepsy patients
      (P = 0.015) and even where the cerebellum appeared macroscopically normal,
      Purkinje cell loss was evident (P = 0.062). Two distinct patterns of atrophy were
      observed, predominantly involving either the anterior or posterior cerebellar
      lobes. Posterior lobe atrophy was more often associated with old fronto-temporal
      contusions and may be post traumatic in aetiology rather than a result of
      excitotoxic damage mediated via cerebro cerebellar pathways. As the majority of
      patients showing either pattern of atrophy had received phenytoin treatment, we
      concluded that it is unlikely that this drug acts alone in inducing the Purkinje
      cell loss.

PMID- 10924870
TI  - Variation of the genes encoding the human glutamate EAAT2, serotonin and dopamine
      transporters and Susceptibility to idiopathic generalized epilepsy.
AB  - Several interacting genetic factors are likely to be involved in the
      epileptogenesis of idiopathic generalized epilepsies (IGE). Neurotransmitter
      transporters play a central role in the fine tuning of neurotransmission by
      removal of released neurotransmitters from the synaptic cleft. The present
      association study tested the hypotheses that variation of the genes encoding
      neurotransmitter transporters confers susceptibility to IGE. The genotypes of 133
      German IGE subjects and 223 ethnically matched controls were assessed for DNA
      polymorphisms of genes encoding the glutamate (EAAT2), the serotonin (SERT), and
      dopamine (DAT) transporters. To increase genetic homogeneity, a subgroup of 76
      patients with idiopathic absence epilepsy (IAE) was analyzed separately. We found
      no evidence for an allelic association of either the silent G603A substitution
      polymorphism in exon 5 of the EAAT2 gene or the regulatory promoter polymorphism
      of the SERT gene with either IGE or IAE. The frequency of the nine-copy allele of
      the 40 base pair repeat polymorphism in the 3' un pop popd region of the DAT gene
      was significantly increased in the IGE patients (chi2 = 4.11, degrees of freedom
      (d.f.) = 1, P = 0.043) and, in particular, in the IAE patients (chi2 = 7.81, d.f.
      = 1, P = 0.005) compared with the controls. The present findings strengthen
      previous evidence that genetic variation of the DAT gene modulates neuronal
      network excitability and contributes to the epileptogenesis of IAE.

PMID- 10924872
TI  - Effects of ewe age and season of lambing on prolificacy in US Targhee, Suffolk,
      and Polypay sheep.
AB  - Factors affecting ewe prolificacy (number of lambs born per ewe lambing) were
      evaluated using records on 9705 Targhee, 12,721 Suffolk, and 7231 Polypay
      lambings from flocks participating in the US National Sheep Improvement Program.
      Factors considered were ewe age and season of lambing. Prolificacy was affected
      by age of the ewe (P<0.001) and was highest for ewes lambing between 4 and either
      7 (Polypay) or 8 (Targhee and Suffolk) years of age. Effects of lambing at
      younger ages were similar for Targhee and Polypay. Relative to mature ewes,
      prolificacy was reduced by 0.6-0.7 lambs in 1-year-old ewes, about 0.3 lambs in 2
      year-old ewes and about 0.1 lambs in 3-year-old ewes. Effects of ewe age were
      smaller in Suffolk, with reductions relative to mature ewes of 0.47, 0.13, and
      0.01 lambs in 1-, 2-, and 3-year-old ewes. Prolificacy of older (>8-year-old)
      ewes was consistently reduced by 0.17-0.20 lambs relative to adult ewes. Within
      the 1-year-old age class, age in months further affected prolificacy of Suffolk
      and Polypay but not Targhee ewes. For these two breeds, prolificacy of 15-month
      old ewes averaged 0.21 lambs more than that observed for 12-month-old ewes.
      Seasonal differences in prolificacy were large for Targhee and Polypay (P<0.001)
      but not for Suffolk (P=0.23) and the distribution of lambings among seasons
      differed (P<0.001) for all breeds. 22% of adult Polypay ewes, but only 1% of
      Targhee and Suffolk ewes lambed in summer and autumn. Prolificacy was highest in
      winter and spring lambings (December through May) and did not differ importantly
      among months within this period. Average prolificacy of 3- to 6-year-old ewes
      lambing in winter and spring was 1.75 for Targhee, 1.91 for Suffolk, and 2.13 for
      Polypay. For age groups with at least 10 observations, prolificacy in autumn
      (September through November) was reduced by an average of 0.14 lambs in Suffolk
      and 0.24 lambs in Polypay (very few Targhee lambed in autumn). Prolificacy in
      summer (June through August) was reduced by an average of 0.18 lambs in Targhee
      and 0.31 lambs in Polypay (very few Suffolks lambed in summer). Adjustment of
      prolificacy records for effects of ewe age is therefore necessary in genetic
      evaluation programs. Seasonal effects on prolificacy are probably best handled by
      placing ewes that lamb in different seasons in different contemporary groups.

PMID- 10924871
TI  - Expression of mRNAs encoding for 17beta-hydroxisteroid dehydrogenase isozymes 1,
      2, 3 and 4 in epileptic human hippocampus.
AB  - Sex steroid hormones exert important influences on neuroendocrine and behavioural
      brain function. As neuroactive steroids they are able to modify neuronal
      excitability. Unbalanced synthesis may thus be implicated in pathophysiological
      conditions, such as epilepsy, migraine, depression and anxiety. In sex steroid
      metabolism, 17beta-hydroxisteroid dehydrogenases (17beta-HSDs) play a crucial
      role in catalyzing the final steps of androgen and estrogen biosynthesis. The
      hippocampus appears to be a major target area of neurosteroidal action. The
      expression of 17beta-HSD isozymes has not yet been studied in human hippocampus.
      Therefore, we investigated the expression of 17beta-HSD 1, 2, 3 and 4 mRNAs in
      hippocampal tissue specimens obtained at neurosurgery from 42 patients with
      pharmacoresistant temporal lobe epilepsy. A competitive RT-PCR assay was used to
      quantify the mRNA transcript level. 17beta-HSD 1 mRNA concentrations were 10000
      fold lower in the hippocampus compared to placental tissue, whereas 17beta-HSD 3
      mRNA concentrations were 50 fold lower than in testis and 17beta-HSD 4
      concentrations were in the same order of magnitude as in liver. 17beta-HSD 2 mRNA
      was not expressed. 17beta-HSD 1, 3 and 4 mRNA concentrations in the hippocampus
      showed no significant differences between men and women and there were no
      significant differences in expression levels of these enzymes between patients
      with Ammon's horn sclerosis (AHS) and those with histopathologically normal
      hippocampus associated with extrahippocampal lesions. No significant correlation
      could be detected between duration of epilepsy, individual seizure frequency and
      expression levels of 17beta-HSDs. In conclusion, the present study is the first
      to demonstrate mRNA expression of 17beta-HSD 1, 3 and 4 in the epileptic human
      hippocampus. Together with data on 5alpha-reductase 1, 3alpha-hydroxisteroid
      oxidoreductase 2 and cytochrome P450scc, previously shown to be expressed in the
      human hippocampus also, our data provide further evidence for the existence of
      sex steroid formation and metabolism in this specific brain area.

PMID- 10924873
TI  - Seasonal effects on puberty and reproductive characteristics of female Chios
      sheep and Damascus goats born in autumn or in February.
AB  - Ten Chios ewe lambs and 10 Damascus she-kids born in October-November and similar
      numbers born in February along with eight multiparous females from each species,
      were used to examine pubertal events and reproductive seasonality. Reproductive
      activity was monitored by determining serum progesterone concentrations once a
      week for 12 months. The mean date of onset of ovulation (puberty) in autumn-born
      Chios females (7 August) was earlier (p<0.05) than in February-born ones (11
      September) though the onset of regular cyclicity was not significantly different
      between the two groups (30 August and 19 September, respectively). The age and
      live weight at puberty in autumn-born females was higher (p<0.01) than in
      February-born ones, the respective values being 43.3 weeks and 50.1kg, versus
      29.9 weeks and 42.0kg. All animals, irrespective of time of birth, started
      ovulating after the summer equinox. Multiparous Chios ewes had reproductive
      cycles covering most time of the year with acyclic periods during spring and
      summer. In ewe lambs, about half of the animals ceased cycling during the second
      half of winter and in spring, while the rest continued cycling. The total number
      of cycles detected over the experimental period was lower (p<0.05) for February
      born (n=9.4) compared with autumn-born females (n=13.7) and adult ewes (n=17.1).
      In Damascus she-kids born in autumn or in February, onset of puberty was at the
      same time in the following autumn, the respective mean date for the two groups
      being 1 November and 27 October. For autumn-born animals, age (48.4 weeks) and
      live weight (53.8kg) at puberty were higher (p<0.01) than for those born in
      February (37.3 weeks, 42.9kg). Reproductive cycles in adult goats started in the
      second half of September and continued until the end of March. Most young goats
      (75%) had their last seasonal cycle in February and the rest in March. The total
      number of cycles was higher (p<0.01) in adult (n=8.1) than in young goats born
      either in autumn (n=6.3) or in February (n=5.7). It is concluded that
      reproductive development and puberty in Chios female sheep are mostly under
      seasonal influences though age and body weight are also contributing factors.
      This breed has a long reproductive season with some animals cycling throughout
      the year. The Damascus female goat is strictly seasonal with distinct periods of
      reproductive cyclicity and inactivity. Puberty attainment of Damascus females
      born in autumn or in February is at the same time the following autumn.

PMID- 10924874
TI  - Effects of dietary level of Leucaena leucocephala on performance of Angora and
      Spanish doelings.
AB  - Thirty Angora (16+/-2kg initial body weight) and 20 Spanish doelings (19+/-2kg
      initial body weight), approximately 8 months of age, were used in an 10 week
      experiment to evaluate effects of dietary level of Leucaena leucocephala on body
      weight (BW) gain and fiber growth. The control diet (CS) included 9% dry matter
      (DM) of formaldehyde-treated casein; other diets consisted of 15, 30, 45 or 60%
      DM of leucaena leaf meal (0.75% mimosine; 15, 30, 45 and 60l, respectively).
      Diets were formulated to be 2.13Mcal metabolizable energy/kg DM, and ranged in
      crude protein from 10 to 14% of DM. DM intake was greater (P<0.05) for 45l than
      for CS and 15l (710, 648, 815, 899 and 811g per day for CS, 15, 30, 45 and 60l,
      respectively) and similar (P>0.05) between Angora and Spanish doelings. BW gain
      was similar (P>0.05) among diets (48, 28, 38, 34 and 26g per day for CS, 15, 30,
      45 and 60l, respectively) and between breeds. Mohair growth rate was lower
      (P<0.05) for 60 and 30l than for CS (1.34, 1.18, 0.94, 1.16 and 0.88mgcm(-2) per
      day, and mohair diameter was greatest (P<0.05) for CS and lowest (P<0.05) for 60l
      (27.7, 25.9, 25.1, 25.0 and 23.8um for CS, 15, 30, 45 and 60l, respectively).
      Cashmere growth rate and fiber diameter for Spanish goats were similar among
      diets, and primary and secondary follicle activities for both Angora and Spanish
      goats were not affected by dietary treatments (P>0.05). Diet affected (P<0.05)
      plasma concentrations of urea, threonine, arginine, valine, phenylalanine,
      isoleucine, leucine and lysine, with concentrations increasing as dietary level
      of leucaena increased. In conclusion, diets of moderate to high levels (e.g.,
      45%) of leucaena with 0.75% mimosine can be fed to goats without adverse effects
      on BW gain or fiber growth. However, further study of the composition of leucaena
      based diets appears necessary to achieve most efficient utilization.

PMID- 10924875
TI  - Effects of dietary protein sources on mohair growth and body weight of yearling
      Angora doelings.
AB  - Fifty-one yearling Angora doelings (20+/-0.6kg initial body weight (BW)) were
      used to determine effects of different dietary protein sources on BW change and
      mohair growth. Diets consisted of approximately 40% roughage and 18-19% CP (DM
      basis), of which two-thirds was supplied by corn gluten meal (CG), cottonseed
      meal (CT), hydrolyzed feather meal (FT) or menhaden fish meal (FI); DM intake was
      restricted at approximately 0.7kg/day. During the 94-day experiment, fleece-free
      ADG was greatest (P<0.05) for FI (35, 33, 35 and 50g), whereas greasy fleece
      weight was greatest (P<0.05) for CG (4.4, 3.6, 3.4 and 3.4kg for CG, CT, FT and
      FI, respectively). Likewise, mohair growth rate was greatest among treatments
      (P<0.05) for CG in each of the three 31- or 32-day periods. Ruminal fluid ammonia
      N concentration was 8, 11, 6 and 13mg/dl (S.E. 1) immediately before feeding; 10,
      18, 11 and 23mg/dl (S.E. 2) at 2h after feeding; 8, 15, 10 and 18mg/dl (S.E. 2)
      at 4h after feeding; and 4, 6, 5 and 8mg/dl (S.E. 1) at 6h after feeding for CG,
      CT, FT and FI, respectively. Total VFA concentration in ruminal fluid was similar
      among treatments (P>0.05) at 4 and 6h, but was generally lower for CG and FT than
      for CT and FI immediately before feeding (29, 33, 26 and 37mM; S.E. 2) and at 2h
      after feeding (44, 57, 45 and 51mM for CG, CT, FT and FI, respectively; S.E. 3).
      In conclusion, the different protein supplements had dissimilar effects on ADG
      (greatest for FI) and mohair growth (greatest for CG). Factors responsible for
      these results are unclear, and the range of experimental or production conditions
      under which comparable findings might occur are unknown and deserve further
      study.

PMID- 10924876
TI  - Effects of underfeeding and refeeding on offals weight in the Barbary ewes.
AB  - The influence of long-term (161 days) underfeeding and refeeding (154 days) on
      the weight of offal components, and digestive content, was studied in 26 adult
      Barbary ewes. Effects on the protein and mineral content of offals were also
      measured. Animals were split in three groups: one was fed hay at maintenance
      level (M), another also received vetch-oat hay to cover 0.2 of maintenance energy
      requirements (L), and the third one was fed at 0.2 of maintenance requirements
      during 161 days, then refed at 1.3 times of energy requirements with a diet of
      hay and barley grain (LH) during 154 days. Underfed animals body weight (BW) at
      slaughter was 31kg. Animals of groups M and LH were slaughtered at similar BW
      (50kg). Underfeeding reduced empty BW by 38% and the weight of most metabolically
      active organs: skin (40%), blood (31%), rumen (34%) and liver (19%), but not
      others (small intestine). Total offals weight was reduced by 27%. Overfeeding of
      previously underfed animals (LH) induced a significant increase in liver weight
      in comparison to M group (18%), owing to a higher nutrient supply. The amount of
      protein in offals and their fat-free weight were decreased by underfeeding,
      whereas the amount of minerals was significantly modified only in components rich
      in bone. These results showed that splanchnic organ mass decreases with
      underfeeding which leads to energy requirements decrease and contributes towards
      resistance of Barbary ewes to harsh food conditions.

PMID- 10924877
TI  - The relationship between semen quality and mineral composition of semen in
      various ram breeds.
AB  - Semen was collected during the breeding season from rams by electroejaculation
      from two native (13 Najdi and 8 Naemi) and three imported (6 Merino, 7 Somalian
      and 9 Sudanese) sheep breeds. There was a marked reduction in sperm concentration
      and the percentage live spermatozoa (p<0.01) produced by the Somalian (Barbari)
      and Sudanese (Sawakni) breeds. On the other hand, these two breeds showed the
      highest percentage of spermatozoal individual motility (p<0.05) and the highest
      concentrations of sodium (Na) chloride (Cl) and inorganic phosphorus (P) in the
      whole semen, seminal plasma and spermatozoa. Superior sperm density, percentage
      live spermatozoa and seminal concentrations of potassium (K) and calcium (Ca)
      were evidenced in the Najdi, Naemi and to a lesser extent, in the Merino rams.
      The biological effects of these inorganic constituents, together with magnesium
      (Mg), in the semen on semen quality should be considered in the interpretation of
      the results obtained in the fertility evaluation of the various ram breeds.

PMID- 10924878
TI  - Uterine contraction patterns and fertility in early postpartum ewes.
AB  - Three experiments were conducted to determine: (1) the direction of uterine
      contractions in Days 32 and 52 postpartum ewes (Experiment 1); (2) the effect of
      PGF(2alpha) on direction of uterine contractions (Experiment 2); and (3) the
      effect of PGF(2alpha) on fertility rates in Day 32 postpartum ewes (Experiment
      3). In Experiment 1, non-lambing (>90 days postpartum) and lambing ewes (day of
      lambing=Day 0) received medroxyprogesterone acetate (MAP) vaginal sponges for 8
      days and 500 IU of eCG at sponge withdrawal (Days 30 or 50 postpartum). At the
      time of eCG injection, ewes were divided into the following groups: (1) non
      lambing (control; n=29); (2) Day 32 postpartum dry (n=15) and lactating (n=16);
      and (3) Day 52 postpartum dry (n=14) and lactating (n=16). At estrus or 60h post
      eCG, the uterus was exteriorized through a mid-ventral incision, and the origin
      and direction of uterine contractions were recorded for 10min. In Experiment 2,
      ewes received MAP sponges on Day 16 postpartum followed by 500 IU of eCG on day
      of sponge removal (Day 30). At estrus, the ewes were divided into the following
      treatments: (1) two injections of saline 4h apart (n=10) and (2) 12.5mg of
      PGF(2alpha) followed by another 12.5mg 4h later (n=7). After the second
      injection, ewes were laparotomized and uterine contractions were counted. In
      Experiment 3, estrus was induced in postpartum ewes, and ewes were mated to two
      rams, then received the same two treatments as described in Experiment 2
      (ram+saline; n=32 and ram+PGF(2alpha); n=28). Two days following mating, ewes
      were laparotomized and the oviducts flushed for recovery of ova. In Experiment 1,
      lactational status had no effect, therefore, the data were pooled. Control ewes
      had a greater percentage (p<0.05) of uterine contractions (69%) moving towards
      the oviducts than did Day 32 (8%) or Day 52 (43%) ewes. In Experiment 2,
      PGF(2alpha) treatment increased the proportion of contractions (p<0.05) moving
      toward the oviducts (controls 16%, PGF(2alpha) 42%). Number of PGF(2alpha)
      treated ewes (Experiment 3) with fertilized ova were not significantly different
      from the control ewes (5/32 versus 2/28; respectively). In conclusion, it can be
      said that the direction of uterine contractions moving toward the oviducts
      increased as the postpartum interval progressed or if they received PGF(2alpha)
      injection. PGF(2alpha) treatment did not improve fertility rates in Day 32
      postpartum ewes.

PMID- 10924879
TI  - Effects of testicular status and feeding diets containing date palm by-product on
      the sensory attributes of Omani lamb meat.
AB  - The effects of testicular status and diet on the tenderness and flavour intensity
      of Omani lamb meat were evaluated. Thirty male lambs were divided into three
      testicular status treatments shortly after birth, entire, castrated or induced to
      cryptorchidism. The animals were fed a maize and soya bean meal based diet,
      isocalorically supplemented with either palm fronds or Rhodesgrass hay. The
      animals were slaughtered at an average age of 161days and weight of 27.6kg.
      Sensory evaluation of meat for tenderness and intensity of flavour were
      undertaken using descriptive analysis with unstructured scales. Meat from New
      Zealand lambs was also evaluated for comparison. Meat from castrated lambs tended
      to be more tender than meat from either entire or cryptorchid lambs. This effect
      was related to the significantly lower daily weight gains, lower carcass weight
      and lower intermuscular fat content of castrated lambs. The effect of induced
      cryptorchidism or inclusion of date frond was not significant on tenderness, nor
      flavour of the lamb meat. Meat from New Zealand lambs was significantly more
      tender, but similar in flavour compared to Omani lambs.

PMID- 10924880
TI  - Effects of season on fleece traits of Angora does in the US.
AB  - Twenty nonpregnant Angora does were used to determine seasonal effects on fleece
      traits, including fiber growth and follicle activity. Does grazed pastures and
      were supplemented with a 50% concentrate diet at a level near that required for
      BW maintenance. Clean fiber growth rate was greatest (p<0.05) among seasons in
      summer and lowest (p<0.05) in winter (1.13, 0.85, 0.98 and 1.20mg/cm(2) per day
      for autumn, winter, spring and summer, respectively); seasonal differences in
      fiber diameter were similar (34.9, 31.7, 33.7 and 36.5um for autumn, winter,
      spring and summer, respectively). Fleece fiber medullation was greatest (p<0.05)
      in summer (0.48, 0.32, 0.40 and 0.76%), and medullated fiber diameter was greater
      in spring and summer than winter (69, 65, 73 and 71um for autumn, winter, spring
      and summer, respectively). Primary follicle activity varied with season more than
      did activity of secondary follicles (primary: 74, 23, 79 and 99%; secondary: 97,
      86, 94 and 99%; for autumn, winter, spring and summer, respectively). In summary,
      Angora goats in the US appear to exhibit seasonal follicle and fiber growth
      cycles, the knowledge of which may improve future nutritional management for
      efficient feed use in mohair production. The optimal time of shearing US Angoras
      for minimal contamination with medullated fibers may be just before spring and
      autumn equinoxes when it is likely that medullated fibers have been recently
      shed.

PMID- 10924881
TI  - Follicle characteristics, seasonal changes in fibre cross-sectional area and
      ellipticity in Australasian specialty carpet wool sheep, Romneys and Merinos.
AB  - Data was collected on secondary:primary follicle ratio, relative follicle
      density, and seasonal changes in fibre cross-sectional area and fibre ellipticity
      (ratio of major-to-minor fibre cross-sectional axis) in the Australasian
      specialty carpet wool breeds (Carpetmaster, Drysdale, Elliottdale, Tukidale),
      Romneys and Merinos. Merinos had a higher secondary:primary follicle ratio
      (p<0.001), relative primary follicle density (p<0.05), relative secondary and
      relative total follicle density (p<0.01) than the other breeds. Both breed and
      follicle type (primary or secondary) had a significant effect on fibre cross
      sectional area (p<0.05). While both fibre types (primary and secondary) showed
      changes in cross-sectional area during the experiment, a more distinct seasonal
      pattern was seen in the secondary fibres with summer maxima and winter minima in
      all breeds. Relative change in fibre diameter was higher in secondary fibres than
      in primary fibres. Changes in fibre ellipticity were also noted throughout the
      duration of the experiment. It is apparent that there are differences between
      primary and secondary follicle populations in the way the fibres produced
      contribute to seasonal changes in average fibre diameter of fleeces. The changes
      suggest there are separate control mechanisms for each follicle type and that the
      number, size and arrangement of the cells in each type of fibre vary
      independently of one another throughout the year, bringing about dynamic changes
      in fibre growth and form. Further work is required to examine the influence of
      feed quality on these factors and to determine the mechanisms through which these
      changes in fibre structure are brought about.

PMID- 10924882
TI  - Evaluation of arid region browse species from north eastern Nigeria using pen fed
      goats.
AB  - Four 18-26 months old castrated Borno whitexSokoto Red goats were used in a 4x4
      Latin square design to measure the dry matter intake (DMI), daily body weight
      change and dry matter digestibility (DMD) of four native Nigerian browse species,
      (Ziziphus spinochrist, Wild., Acacia albida, Del., Sterculia satigera, Guill. and
      Anogeissus licocarpus, Guill.) native to the semi-arid regions. The mean DMI of
      Z. spinochrist, Wild. and A. albida, Del. were similar but higher than for S.
      satigera, Guill. and A. licocarpus, Guill. The DMD of A. licocarpus,Guill. was
      lower (p<0.05) than for Z. spinochrist, Wild., Acacia licocarpus, Del. or S.
      satigera, Guill. The lowest body weight gain recorded was for A. licocarpus,
      Guill.; this was attributed to the larger amount of fibre in the forage resulting
      in a slow rate of cell wall degradation and rumen digestibility. Goats showed no
      visual signs of toxicosis. This study suggests that A. albida, Del. has the
      highest forage value for goats followed by Z. spinochrist, Wild., S. satigera,
      Guill. and A. licocarpus, Guill. Potentially the species examined can provide
      feed for goats as well as for other small ruminants during long dry periods when
      other feed is unavailable.

PMID- 10924883
TI  - Prenatal development of ovine fetus.
AB  - From 39 gravid ovine genitalia in various stages of gestation, collected from a
      local slaughter house in Srinagar city, 37 and 4 fetuses were obtained from
      single and twin pregnancies, respectively. The genitalia collected were divided
      into four stages of gestation as: Stage- I (30-60 days); Stage-II (61-90 days);
      Stage-III (91-120 days); and Stage-IV (120 days to term).Various measurements of
      gravid genitalia, like diameter of pregnant horn, size of ovaries, consistency of
      corpus luteum, volume of fetal fluids, diameter of largest cotyledon, crown anus
      length and length of long bones were recorded. The largest diameter of pregnant
      horn averaged 8.1+/-1.2, 13.9+/-0.09, 17.8+/-0.04 and 23.2+/-0.06cm at stages-I,
      II, III and IV, respectively. The length of ovaries recorded was 1.4+/-0.03,
      1.7+/-0.06, 1.6+/-0.06 and 2.0+/-0.2cm at the four stages of gestation,
      respectively. The breadth of ovaries varied from 1.0+/-0.03, 1.2+/-0.03, 1.2+/
      0.05 and 1.5+/-0.02cm at the four stages of gestation, respectively. The
      thickness of ovaries at the four stages of gestation were 0.7+/-0.02, 0.8+/-0.03,
      0.8+/-0.03 and 0.9+/-0.06cm, respectively. The volume of fetal fluids at the four
      stages of gestation recorded was 64+/-15, 256+/-34, 287+/-25 and 502+/-29ml in
      allantoic fluid and 22+/-6, 128+/-50, 304+/-22 and 353+/-51ml in amniotic fluid,
      respectively. The mean crown anus length observed with advancing stages of
      gestation was 6.7+/-0.9, 10.1+/-1.3, 31.5+/-0.09 and 46+/-1.2cm, respectively.
      The mean observed length of Radium from Stage-I to Stage-IV were 1.6+/-0.6, 2.6+/
      0.03, 5.5+/-0.2 and 8.9+/-0.03cm, respectively, while that of Tibia was 2.1+/
      0.1, 3.4+/-0.4, 7.3+/-0.3 and 12+/-0.3cm, respectively.

PMID- 10924884
TI  - The effect of enzymes on semen viscosity in Llamas and Alpacas.
AB  - The effect of four enzymes: collagenase, fibrinolysin, hyalurodinase, and trypsin
      were recorded on the viscosity, motility, percent live spermatozoa and acrosome
      integrity of Llama and Alpaca semen. Semen samples were collected using a
      modified artificial vagina for each of the five llamas and five alpacas. A 25%
      solution of the of enzyme at a concentration of 1mg/ml was added to the
      ejaculate. Analysis of variance was used to determine differences in eliminating
      viscosity and alterations in motility, percent live spermatozoa and the acrosomal
      integrity at 0 (time of semen collection), 2 and 5min. In Llama and Alpaca semen,
      collagenase eliminated viscosity in 100 and 99% of the samples, respectively.
      Correspondingly, fibrinolysin in 89 and 59%; hyalurodinase in 88 and 36%; and
      trypsin in 55 and 68% of the samples (p<0.05). In the Llama sperm, motility
      decreased (p<0.05) with the addition of fibrinolysin (28%), trypsin (13%),
      hyalurodinase (12%), and collagenase (4%). In Alpaca semen, the enzymes used had
      no effect on sperm motility. Percent live spermatozoa variably decreased after
      the addition of fibrinolysin, hyalurodinase and trypsin. There was no significant
      difference in the acrosome integrity in Llama and Alpaca makes following the
      addition of the enzymes. Overall, collagenase had little or no influence in
      decreasing motility, percent live spermatozoa and acrosome integrity, whereas, it
      was effective in eliminating semen viscosity.

PMID- 10924885
TI  - Erratum to "Carbon and nitrogen balance studies in Muzaffarnagari sheep fed diets
      varying in roughage and concentrate ratio"

PMID- 10924886
TI  - Novel aspects of the pharmacokinetics and pharmacodynamics of analgesic drugs.

PMID- 10924887
TI  - Methadone: a review of its pharmacokinetic/pharmacodynamic properties.
AB  - During the past decades the use of methadone has been increased as a result of
      the interest of optimizing its therapeutics in opioid addicts, one of the groups
      with higher risk for AIDS infection. However standard dose of methadone are far
      from being the appropriate for relief pain or prevent withdrawal signs in
      maintenance programs in many patients. To achieve an optimal dose regimen for an
      individual, the knowledge of the relationship between the
      pharmacokinetics/pharmacodynamics (pk/pd) drug properties and the demographic and
      physiopathological characteristics of the subject is required. Unfortunately,
      there is a lack of studies dealing with the population pk/pd properties of
      methadone. In the current study, a review of the pk/pd properties of methadone is
      presented with the aim of understanding the sources of variability in response.
      This will help in the design of prospective pk/pd studies; in particular,
      individual data including sex, weight, alpha(1)-acid glycoprotein levels in
      plasma, concomitant medications, time after starting treatment with methadone and
      previous exposure to other opioids should be requested. In addition, designs for
      drug administration should allow the characterization of the plasma-versus
      biophase distribution and the development of tolerance processes. Because
      methadone is usually administered as a racemic mixture, the use of
      enantioselective techniques to determine both enantiomers in plasma is also
      highly recommended.

PMID- 10924888
TI  - A review of the pharmacokinetic and pharmacodynamic factors in the potentiation
      of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by
      caffeine.
AB  - Caffeine is an effective analgesic adjuvant because it increases the
      antinociceptive effect of NSAIDs while reducing the probability of side effects.
      The mechanism by which caffeine increases the antinociceptive action of NSAIDs
      does not appear to include a pharmacokinetic interaction. The potentiation
      appears to be due to a pharmacokinetic mechanism including actions at the central
      and the peripheral levels. Because caffeine shifts the effect-compartment
      concentration-effect relation of NSAIDs to the left and this relationship is
      sigmoidal, there is no potentiation if the NSAID concentrations are too high or
      too low with respect to EC(50). The best potentiation can be observed if the
      NSAID doses used yield effect-compartment concentrations in the vicinity of
      EC(50). Therefore further investigation of the PK/PD relations of caffeine-NSAID
      combinations for different pain states and intensities is needed to optimize the
      therapeutic use of these mixtures.

PMID- 10924889
TI  - Characterization of the potentiation of the antinociceptive effect of diclofenac
      by vitamin B complex in the rat.
AB  - The role of vitamin B complex preparations as an analgesic adjuvant is
      controversial. Therefore, the purpose of the present study was to characterize
      the potentiation of the antinociceptive effect of diclofenac by a vitamin B
      complex preparation and its individual components by using the pain-induced
      functional-impairment model in the rat (PIFIR). Pain was produced by the
      intraarticular injection of uric acid in the right hind limb. Oral administration
      of diclofenac resulted in a dose-dependent antinociceptive effect. Oral
      administration of a vitamin B complex preparation containing thiamine (vitamin
      B(1)), pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) in a
      1:1:0.01 proportion did not produce any antinociception by itself, but it
      significantly potentiated the effect of diclofenac. Coadministration of
      diclofenac with either thiamine or pyridoxine resulted in an antinociceptive
      effect similar to that of diclofenac alone. On the other hand, coadministration
      of cyanocobalamin significantly increased diclofenac-induced antinociception. It
      is concluded that the potentiation of diclofenac-induced antinociception in the
      PIFIR model is due to cyanocobalamin.

PMID- 10924891
TI  - Evidence for the participation of the nitric oxide-cyclic GMP pathway in the
      antinociceptive effect of nimesulide.
AB  - The involvement of the nitric oxide-cyclic GMP pathway in the peripheral
      antinociception induced by the COX-2 preferential inhibitor nimesulide was
      assessed by using the formalin test in the rat. Intraplantar administration of
      nimesulide in the formalin-injured paw produced a significant antinociceptive
      effect that was due to a local action, because nimesulide administration in the
      contralateral paw was ineffective. Local pretreatment of the paws with saline or
      N(G)-D-nitro-arginine methyl ester (D-NAME, the inactive isomer of L-NAME) did
      not affect the antinociception produced by nimesulide. However, local
      administration of L-NAME (a nitric oxide synthesis inhibitor) or 1H-(1,2,4)
      oxadiazolo(4, 2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor)
      blocked the effect of nimesulide. Moreover, the antinociceptive effect of local
      nimesulide was potentiated by the coadministration of 3-morpholino-sydnonimine
      HCl (SIN-1, a nitric oxide donor). It is concluded that nimesulide produces
      antinociception by a peripheral mechanism of action requiring activation of the
      nitric oxide-cyclic GMP pathway at the local level.

PMID- 10924890
TI  - Evidence for a peripheral mechanism of action for the potentiation of the
      antinociceptive effect of morphine by dipyrone.
AB  - The potentiation of the antinociceptive effect of morphine by dipyrone
      (metamizol) and the possible participation of a peripheral mechanism on such
      synergism were studied with the use of the formalin test in the rat. Nociception
      was induced by the intraplantar injection of diluted formalin (1%) in the right
      hind paw. Local administration of either dipyrone or morphine in the site of
      injury produced a dose-dependent antinociceptive effect. When combined,
      noneffective doses of morphine (1.25 microg/paw) and dipyrone (100 microg/paw)
      produced a significantly greater antinociceptive effect compared with either drug
      alone or saline. The opioid antagonist naloxone partly reversed the effect of the
      dipyrone-morphine combination. On the other hand, the inhibitor of nitric oxide
      (NO) synthesis, N(G)-L-nitro-arginine methylester (L-NAME), but not its inactive
      isomer, D-NAME, completely antagonized the effect of the dipyrone-morphine
      combination. These results suggest that the potentiation of morphine-induced
      antinociception by dipyrone in the formalin test requires an important
      participation of local release of NO, activating the NO-cyclic GMP pathway at the
      peripheral level.

PMID- 10924892
TI  - Effect of experimental spinal cord injury on salicylate bioavailability after
      oral aspirin administration.
AB  - The purpose of the present work was to study whether spinal cord injury (SCI)
      alters salicylate bioavailability after oral aspirin administration. Female
      Sprague-Dawley rats were subjected to SCI at the T8 level by two procedures,
      contusion by the weight-drop method and severance by knife, and received a single
      oral aspirin dose (15 mg/kg) 24 h after injury. Blood samples were drawn and
      aspirin (ASA) and salicylic acid (SA) concentrations in whole blood were
      determined at selected times over a period of 240 min. Both SCI procedures
      produced similar alterations on salicylate bioavailability. ASA bioavailability
      was not significantly changed by SCI. On the other hand, SA peak concentrations
      were significantly reduced in 20% to 30%, compared with sham-lesioned controls.
      The area under the SA concentration against time curve was decreased in 10% to
      25%, although this difference did not reach statistical significance. Results
      suggest that SCI at the T8 level decreases the rate, but not the extent, of
      aspirin absorption from the gastrointestinal tract. SCI-induced alterations in
      aspirin absorption appeared to be modest compared with those previously reported
      for other analgesic agents, such as paracetamol (acetaminophen).

PMID- 10924893
TI  - Bioavailability of diclofenac after intramuscular administration to rats with
      experimental spinal cord injury.
AB  - Spinal cord injury (SCI) has been proposed to reduce drug bioavailability after
      intramuscular administration owing to an impairment in blood flow to paralyzed
      limbs. To test this hypothesis, we studied diclofenac bioavailability after
      intramuscular administration in rats with SCI. Female Sprague-Dawley rats were
      submitted to SCI at the T8 level by contusion and received a 10-mg/kg
      intramuscular diclofenac dose in the thigh of the right hind limb 24 h after
      injury. Blood samples were drawn, diclofenac concentration was determined by high
      performance liquid chromatography, and whole-blood concentration against time
      curves were constructed. SCI did not result in a significant change in C(max) and
      T(max), compared with sham-lesioned controls, suggesting that the rate of drug
      absorption was not altered. Half-life was prolonged, and therefore area under the
      curve was greater in SCI than in sham-lesioned animals. Therefore, 24 h after SCI
      at the T8 level, intramuscular diclofenac bioavailability was not impaired but
      was actually enhanced. Results suggest that the rate of intramuscular diclofenac
      absorption is not significantly altered, although its elimination is impaired,
      during the acute phase of SCI. It then appears that SCI-induced pharmacokinetic
      alterations are complex, the global bioavailability depending on the sum of SCI
      effects on absorption, distribution, and elimination. Systematic studies on SCI
      induced alterations are thus required to provide information leading to a
      rational dosing regimen design for SCI patients.

PMID- 10924894
TI  - Influence of sex on the pharmacokinetics of tolmetin in the rat.
AB  - The purpose of this study was to investigate sex-related differences in the
      pharmacokinetics of tolmetin, a potent nonsteroidal anti-inflammatory drug, in
      the rat. Male and female Wistar rats received oral tolmetin at two dose levels,
      3.2 and 10 mg/kg. Blood samples were drawn at selected times after drug
      administration, and tolmetin concentration in whole blood was determined.
      Tolmetin was rapidly absorbed in all cases. C(max) increased with the dose, but
      was similar in both sexes. Notwithstanding, tolmetin half-life was significantly
      prolonged in females compared with males. As a result of the prolonged half-life,
      area under the curve values were significantly higher in females than in males.
      Tolmetin clearance was significantly reduced in females. The present results
      strongly suggest sex-related differences in the pharmacokinetics of tolmetin in
      the rat. Tolmetin elimination appears to be impaired in females, compared with
      males. The existence of sex-related differences in tolmetin pharmacokinetics in
      other species, including humans, requires further investigation.

PMID- 10924895
TI  - Temperature dependence of the formal reduction potential of putidaredoxin.
AB  - Putidaredoxin (Pdx), a [2Fe-2S] redox protein of size M(r) 11,600, transfers two
      electrons in two separate steps from the flavin containing putidaredoxin
      reductase to the heme protein, cytochrome CYP101 in the P450cam catalytic cycle.
      It has recently come to light, through NMR measurements, that there can be
      appreciable differences in the Pdx conformational dynamics between its reduced
      and oxidized states. The redox reaction entropy, deltaS(0')rc = (S(0')Pdx(r)
      S(0')Pdx(0)), as determined from measurements of the variation in formal
      potential with temperature, E0'(T), provides a measure of the strength of this
      influence on Pdx function. We designed a spectroelectrochemical cell using
      optically transparent tin oxide electrodes, without fixed or diffusible
      mediators, to measure E0'(T) over the temperature range 0-40 degrees C. The
      results indicate that the redox reaction entropy for Pdx is biphasic, decreasing
      from -213 +/- 27 J mol(-1) K(-1) over 0-27 degrees C, to -582 +/- 150 J mol(-1) K
      (-1) over 27-40 degrees C. These redox reaction entropy changes are significantly
      more negative than the changes reported for most cytochromes, although our
      measurement over the temperature interval 0-27 degrees C is in the range reported
      for other iron-sulfur proteins. This suggests that Pdx (and other ferredoxins) is
      a less rigid system than monohemes, and that redox-linked changes in
      conformation, and/or conformational dynamics, impart to these proteins the
      ability to interact with a number of redox partners.

PMID- 10924896
TI  - Reduction and protonation of the secondary quinone acceptor of Rhodobacter
      sphaeroides photosynthetic reaction center: kinetic model based on a comparison
      of wild-type chromatophores with mutants carrying Arg-->Ile substitution at sites
      207 and 217 in the L-subunit.
AB  - After the light-induced charge separation in the photosynthetic reaction center
      (RC) of Rhodobacter sphaeroides, the electron reaches, via the tightly bound
      ubiquinone QA, the loosely bound ubiquinone Q(B) After two subsequent flashes of
      light, Q(B) is reduced to ubiquinol Q(B)H2, with a semiquinone anion Q-(B) formed
      as an intermediate after the first flash. We studied Q(B)H2 formation in
      chromatophores from Rb. sphaeroides mutants that carried Arg-->Ile substitution
      at sites 207 and 217 in the L-subunit. While Arg-L207 is 17 A away from Q(B), Arg
      L217 is closer (9 A) and contacts the Q(B)-binding pocket. From the pH dependence
      of the charge recombination in the RC after the first flash, we estimated
      deltaG(AB), the free energy difference between the Q-(A)Q(B) and Q(A)Q-(B)
      states, and pK212, the apparent pK of Glu-L212, a residue that is only 4 A away
      from Q(B). As expected, the replacement of positively charged arginines by
      neutral isoleucines destabilized the Q-(B) state in the L217RI mutant to a larger
      extent than in the L207RI one. Also as expected, pK212 increased by approximately
      0.4 pH units in the L207RI mutant. The value of pK212 in the L217RI mutant
      decreased by 0.3 pH units, contrary to expectations. The rate of the Q-(A)Q-(B)-
      >Q(A)Q(B)H2 transition upon the second flash, as monitored by electrometry via
      the accompanying changes in the membrane potential, was two times faster in the
      L207RI mutant than in the wild-type, but remained essentially unchanged in the
      L217RI mutant. To rationalize these findings, we developed and analyzed a kinetic
      model of the Q-(A)Q-(B)-->Q(A)Q(B)H2 transition. The model properly described the
      available experimental data and provided a set of quantitative kinetic and
      thermodynamic parameters of the Q(B) turnover. The non-electrostatic, 'chemical'
      affinity of the QB site to protons proved to be as important for the attracting
      protons from the bulk, as the appropriate electrostatic potential. The mutation
      caused changes in the chemical proton affinity could be estimated from the
      difference between the experimentally established pK2J2 shifts and the expected
      changes in the electrostatic potential at Glu-L212, calculable from the X-ray
      structure of the RC. Based on functional studies, structural data and kinetic
      modeling, we suggest a mechanistic scheme of the QB turnover. The detachment of
      the formed ubiquinol from its proximal position next to Glu-L212 is considered as
      the rate-limiting step of the reaction cycle.

PMID- 10924897
TI  - Effect of serum albumin on vascular smooth muscle metabolism.
AB  - In studies on metabolism of vascular smooth muscle, it was observed that
      incubation of intact porcine carotid artery strips with 3% bovine or porcine
      serum albumin had profound effects on the oxidation of substrates and O2
      consumption. Arteries incubated over 180 min with charcoal-treated and dialyzed
      albumin demonstrated time-dependent stimulation of glucose oxidation (145%; P <
      0.0001, n=6) and O2 consumption (116%; P< 0.001, n=6). These results were not
      mimicked by incubation with 3% solutions of ovalbumin or porcine skin gelatin.
      However, the oxidation of the medium chain fatty acid octanoate was inhibited in
      the presence of albumin over a broad range of octanoate concentrations (0.5-5.0
      mM). Short chain fatty acid oxidation (acetate, 5 mM), in contrast, was not
      inhibited by albumin. Wash-out of albumin only partially reversed the stimulation
      of O2 consumption and incubation of arteries with a polyanionic compound,
      polyethylene sulfonate (5 mg/ml), blunted the stimulatory effect of albumin on O2
      consumption. Albumin also produced anaplerosis of the Krebs cycle, and an
      increase in the content of glutamate and alanine (P < 0.005, n=8). The metabolic
      effects of albumin were associated with time-dependent uptake of albumin (30.9 +/
      1.5 nmol/g per 210 min; P<0.01, n=15). ATP-dependent proteolysis of the albumin
      taken up was also observed. These results demonstrate novel and important
      intracellular effects of serum albumin on energy metabolism of vascular smooth
      muscle.

PMID- 10924898
TI  - Molecular contacts in the transmembrane c-subunit oligomer of F-ATPases
      identified by tryptophan substitution mutagenesis.
AB  - When isolated in its monomeric form, subunit c of the proton transporting ATP
      synthase of Escherichia coli was shown to fold in a hairpin-like structure
      consisting of two hydrophobic membrane spanning helices and a short connecting
      hydrophilic loop. In the plasma membrane of Escherichia coli, however, about 9-12
      c-subunit monomers form an oligomeric complex that functions in transmembrane
      proton conduction and in energy transduction to the catalytic F1 domain. The
      arrangement of the monomers and the molecular architecture of the complex were
      studied by tryptophan scanning mutagenesis and restrained MD simulations.
      Residues 12-24 of the N-terminal transmembrane segment of subunit c were
      individually substituted by the large and moderately hydrophobic tryptophan side
      chain. Effects on the activity of the mutant proteins were studied in selective
      growth experiments and various ATP synthase specific activity assays. The results
      identify potential intersubunit contacts and structurally non-distorted,
      accessible residues in the c-oligomer and add constraints to the arrangement of
      monomers in the oligomeric complex. Results from our mutagenesis experiments were
      interpreted in structural models of the c-oligomer that have been obtained by
      restrained MD simulations. Different stoichiometries and monomer orientations
      were applied in these calculations. A cylindrical complex consisting of 10
      monomers that are arranged in two concentric rings with the N-terminal helices of
      the monomers located at the periphery shows the best match with the experimental
      data.

PMID- 10924899
TI  - The NADH oxidation domain of complex I: do bacterial and mitochondrial enzymes
      catalyze ferricyanide reduction similarly?
AB  - The hexammineruthenium (HAR) and ferricyanide reductase activities of Complex I
      (H+-translocating NADH:ubiquinone reductase) from Paracoccus denitrificans and
      bovine heart mitochondria were studied. The rates of HAR reduction are high, and
      its steady-state kinetics is similar in both P. denitrificans and bovine Complex
      I. The deamino-NADH:HAR reductase activity of Complex I from both sources is
      significantly higher than the respective activity in the presence of NADH. The
      HAR reductase activity of the bacterial and mitochondrial Complex I is similarly
      and strongly pH dependent. The pK(a) of this activity could not be determined,
      however, due to low stability of the enzymes at pH values above 8.0. In contrast
      to the high similarity between bovine and P. denitrificans Complex I as far as
      HAR reduction is concerned, the ferricyanide reductase activity of the bacterial
      enzyme is much lower than in mitochondria. Moreover, ferricyanide reduction in P.
      denitrificans, but not bovine mitochondria, is partially sensitive to
      dicyclohexylcarbodiimide (T. Yagi, Biochemistry 26 (1987) 2822-2828). On the
      other hand, the inhibition of ferricyanide reduction by high concentration of
      NADH, a typical phenomenon in bovine Complex I, is much weaker in the bacterial
      enzyme. The functional differences between the two enzymes might be linked to the
      properties of their binuclear Fe-S clusters.

PMID- 10924900
TI  - The natural product capsaicin inhibits photosynthetic electron transport at the
      reducing side of photosystem II and purple bacterial reaction center: structural
      details of capsaicin binding.
AB  - Capsaicin, a natural quinone analog, was found to block electron transport, in
      both plant photosystem II (PSII) and bacterial reaction center (RC) from
      Rhodobacter sphaeroides, at the QB site. The mode of action of capsaicin was
      investigated by O2 evolution measurements and fluoresence induction studies in
      the case of PSII, and flash-induced absorbance spectroscopy in the case of the
      bacterial RC. Structural details of capsaicin binding to the bacterial RC complex
      were determined by X-ray crystallographic analysis.

PMID- 10924901
TI  - Binding of detergents and inhibitors to bovine complex I - a novel purification
      procedure for bovine complex I retaining full inhibitor sensitivity.
AB  - Mitochondrial complex I exhibits some peculiar and poorly understood features
      regarding the effects of detergents on activity and sensitivity to hydrophobic
      inhibitors that are not seen with other membrane complexes using ubiquinone as a
      substrate. Therefore, we investigated the interaction of complex I from bovine
      heart mitochondria with different types of detergents by monitoring activity,
      degree of inhibition and inhibitor binding in the presence of increasing
      concentrations of detergent. It is shown that apart from their nature as
      solubilizing and delipidating agents the polyoxyethylene-ether detergents Triton
      X-100, Brij-35 and Thesit act as specific inhibitors of complex I and compete
      with classical complex I inhibitors for a common binding domain. These findings
      were used to develop a novel large-scale chromatographic procedure for isolation
      of inhibitor-sensitive NADH:ubiquinone oxidoreductase (complex I) from bovine
      heart mitochondria. The enzyme was purified by selective solubilization in Triton
      X-100 and subsequent hydroxylapatite, ion-exchange and gel-exclusion
      chromatography. By switching detergents from Triton X-100 to dodecylmaltoside
      after hydroxylapatite chromatography the procedure yields highly pure,
      monodisperse and fully inhibitor-sensitive enzyme.

PMID- 10924902
TI  - Effects of medium polarization and pre-existing field on activation energy of
      enzymatic charge-transfer reactions.
AB  - The highly organized spatial structure of proteins' polar groups results in the
      existence of a permanent intraprotein electric field and in protein's weak
      dielectric response, i.e. its low dielectric constant. The first factor affects
      equilibrium free energy gap of a charge-transfer reaction, the second (medium
      polarization effect) influences both equilibrium and non-equilibrium
      (reorganization) energies, decreasing the latter substantially. In the framework
      of the rigorous 'fixed-charge-density' formalism, the medium polarization
      component of the reaction activation energy has been calculated, both for the
      activation energy of the elementary act proper, and the effective activation
      energy accounting for the charges' transfer from water into a low-dielectric
      structureless medium. In all typical cases of reactions, the energy spent for
      charge transfer from water into structureless 'protein' is larger than the gain
      in activation energy due to the protein's low reorganization energy. Therefore,
      the low dielectric constant of proteins is not sufficient to ensure their high
      catalytic activity, and an additional effect of the pre-existing intraprotein
      electric field, compensating for an excessive charging energy, is necessary. Only
      a combined action of low reorganization energy and pre-existing electric field
      provides proteins with their high catalytic activity. The dependence of
      activation energy on the globule geometry has been analyzed. It is shown that,
      for each reaction, an optimum set of geometric parameters exists. For five
      hydrolytic enzymes, the optimum globule radii have been calculated using the
      experimental geometry of their active sites. The calculated radii agree
      satisfactorily with the real sizes of these macromolecules, both by absolute and
      by relative values.

PMID- 10924903
TI  - One-electron reduction of quinones by the neuronal nitric-oxide synthase
      reductase domain.
AB  - Flavin electron transferases can catalyze one- or two-electron reduction of
      quinones including bioreductive antitumor quinones. The recombinant neuronal
      nitric oxide synthase (nNOS) reductase domain, which contains the FAD-FMN
      prosthetic group pair and calmodulin-binding site, catalyzed aerobic NADPH
      oxidation in the presence of the model quinone compound menadione (MD), including
      antitumor mitomycin C (Mit C) and adriamycin (Adr). Calcium/calmodulin (Ca2+/CaM)
      stimulated the NADPH oxidation of these quinones. The MD-mediated NADPH oxidation
      was inhibited in the presence of NAD(P)H:quinone oxidoreductase (QR), but Mit C-
      and Adr-mediated NADPH oxidations were not. In anaerobic conditions, cytochrome
      b5 as a scavenger for the menasemiquinone radical (MD*-) was stoichiometrically
      reduced by the nNOS reductase domain in the presence of MD, but not of QR. These
      results indicate that the nNOS reductase domain can catalyze a only one-electron
      reduction of bivalent quinones. In the presence or absence of Ca2+/CaM, the
      semiquinone radical species were major intermediates observed during the
      oxidation of the reduced enzyme by MD, but the fully reduced flavin species did
      not significantly accumulate under these conditions. Air-stable semiquinone did
      not react rapidly with MD, but the fully reduced species of both flavins, FAD and
      FMN, could donate one electron to MD. The intramolecular electron transfer
      between the two flavins is the rate-limiting step in the catalytic cycle [H.
      Matsuda, T. Iyanagi, Biochim. Biophys. Acta 1473 (1999) 345-355). These data
      suggest that the enzyme functions between the 1e- <==> 3e- level during one
      electron reduction of MD, and that the rates of quinone reductions are stimulated
      by a rapid electron exchange between the two flavins in the presence of Ca2+/CaM.

PMID- 10924905
TI  - Induction of photochemical auto-reduction of cytochrome-c oxidase by an organic
      peroxide.
AB  - Cytochrome-c oxidase aa3 (CcO) from Paracoccus denitrificans interacts with
      tertiary butyl hydroperoxide (t-Bu-O-O-H, TBHP) by forming an adduct as indicated
      by an absorption shift at 408/432 nm and the induction of photochemical
      autoreduction. The adduct was stable at room temperature for several days even
      under aerobic conditions. Upon irradiation (413 nm) of the adduct, a
      photoproduct, similar to the oxygenated mixed valence species (607 nm form), was
      formed, as indicated by the 418/442 and 607 nm signals in the absorption
      difference spectrum. It is concluded that the adduct formation changes the
      photochemical properties of heme a3. A molecular model for the binding mechanism
      of TBHP to CcO and for the photochemistry of heme a3-TBHP adduct is proposed.

PMID- 10924904
TI  - Chromatographic separation of a small subunit (PsbW/PsaY) and its assignment to
      Photosystem I reaction center.
AB  - By using a hydroxyapatite column, the five major Photosystem I (PSI) subunits
      (PsaA,-B,-C,-D,-E) solubilized by sodium dodecyl sulfate (SDS) were fractionated
      from a spinach PSI reaction center preparation. Another small (5-6 kDa)
      polypeptide was also separated, and purified to homogeneity. Mass spectroscopy
      yielded its molecular weight to be 5942 +/- 10. This polypeptide had an N
      terminal sequence homologous to those of previously reported 5-kDa subunits from
      spinach and wheat and a 6.1-kDa subunit of Chlamydomonas, which had all been
      assigned to Photosystem II (PSII) and designated as PsbW. However, we found
      similar 5-kDa polypeptides with highly conserved N-terminal sequences
      ubiquitously in PSI particles from other plants including Daikon (Raphanus
      sativus, Japanese radish), Chingensai (Brassica parachinensis, Chinese cabbage),
      parsley and Shungiku (Chrysanthemum coronarium, Garland chrysanthemum) as well.
      Preparations of spinach PSI particles prepared by using a mild detergent
      (digitonin) had this 5-kDa subunit, while PSII particles did not. Moreover, a
      bare-bone PSI reaction center preparation consisting of PsaA/B alone had a more
      than stoichiometric amount of this 5-kDa polypeptide. A mechanically (without
      detergent) fractionated stroma thylakoid preparation from Phytolacca americana,
      which lacked other PSII subunits, also contained this 5-kDa subunit. Thus, we
      propose that this 5-kDa polypeptide, previously designated as a PSII subunit
      (PsbW), is an integral subunit of PSI as well.

PMID- 10924906
TI  - Expression of prokaryotic and eukaryotic cytochromes c in Escherichia coli.
AB  - C-type cytochromes from various sources show substantial structural conservation.
      For the covalent attachment of heme groups to apocytochromes, however, three
      different enzyme systems have been described so far. We have examined the ability
      of the heme ligation systems of Escherichia coli and of Saccharomyces cerevisiae
      to process cytochromes from S. cerevisiae, Paracoccus denitrificans, and
      Synechocystis sp. PCC 6803. E. coli's maturation system with at least eight
      different proteins accepted all these cytochromes for heme ligation. The single
      subunit heme lyase from S. cerevisiae mitochondria, on the other hand, failed to
      attach heme groups to cytochromes of prokaryotic origin.

PMID- 10924907
TI  - Excitation energy transfer from phycobilisomes to photosystems: a phenomenon
      associated with the temporal separation of photosynthesis and nitrogen fixation
      in a cyanobacterium, Plectonema boryanum.
AB  - Plectonema boryanum shows temporal separation of photosynthesis and nitrogen
      fixation under diazotrophic conditions. Low temperature fluorescence studies have
      shown that in vivo the nitrogen fixing and photosynthesizing cells are adapted to
      'state 2' and 'state 1', respectively. During nitrogen fixation phycobilisomes
      seem to transfer excitation energy to photosystem I whereas during oxygenic
      photosynthesis the energy is transferred to photosystem II. The state 2 adapted N
      phase cells failed to undergo transition to state 1 while P-phase cells exhibited
      state 1 to state 2 transition. The nitrogen fixing cells showed a decreased level
      ofpsbC transcript, lack of CP47 in thylakoid membrane, and presence of the F685
      peak but absence of the F695 peak in 77 K fluorescence spectra. These results
      suggest that the metabolic and molecular changes associated with nitrogen
      fixation may favor direct energy transfer from the phycobilisomes to photosystem
      I. This should help the organism to achieve low photosystem II and high
      photosystem I activity to set temporal separation of nitrogen fixation and
      photosynthesis for photoautotrophic growth under diazotrophic conditions.

PMID- 10924908
TI  - Control of the photosynthetic electron transport by PQ diffusion microdomains in
      thylakoids of higher plants.
AB  - We investigate the role of plastoquinone (PQ) diffusion in the control of the
      photosynthetic electron transport. A control analysis reveals an unexpected flux
      control of the whole chain electron transport by photosystem (PS) II. The
      contribution of PSII to the flux control of whole chain electron transport was
      high in stacked thylakoids (control coefficient, CJ(PSII) =0.85), but decreased
      after destacking (CJ(PSII)=0.25). From an 'electron storage' experiment, we
      conclude that in stacked thylakoids only about 50 to 60% of photoreducable PQ is
      involved in the light-saturated linear electron transport. No redox equilibration
      throughout the membrane between fixed redox groups at PSII and cytochrome (cyt)
      bf complexes, and the diffusable carrier PQ is achieved. The data support the PQ
      diffusion microdomain concept by Lavergne et al. [J. Lavergne, J.-P. Bouchaud, P.
      Joliot, Biochim. Biophys. Acta 1101 (1992) 13-22], but we come to different
      conclusions about size, structure and size distribution of domains. From an
      analysis of cyt b6 reduction, as a function of PSII inhibition, we conclude that
      in stacked thylakoids about 70% of PSII is located in small domains, where only 1
      to 2 PSII share a local pool of a few PQ molecules. Thirty percent of PSII is
      located in larger domains. No small domains were found in destacked thylakoids.
      We present a structural model assuming a hierarchy of specific, strong and weak
      interactions between PSII core, light harvesting complexes (LHC) II and cyt bf.
      Peripheral LHCII's may serve to connect PSII-LHCII supercomplexes to a flexible
      protein network, by which small closed lipid diffusion compartments are formed.
      Within each domain, PQ moves rapidly and shuttles electrons between PSII and cyt
      bf complexes in the close vicinity. At the same time, long range diffusion is
      slow. We conclude, that in high light, cyt bfcomplexes located in distant stromal
      lamellae (20 to 30%) are not involved in the linear electron transport.

PMID- 10924909
TI  - Diphenylene iodonium as an inhibitor for the hydrogenase complex of Rhodobacter
      capsulatus. Evidence for two distinct electron donor sites.
AB  - The photosynthetic bacterium Rhodobacter capsulatus synthesises a membrane-bound
      [NiFe] hydrogenase encoded by the H2 uptake hydrogenase (hup)SLC structural
      operon. The hupS and hupL genes encode the small and large subunits of
      hydrogenase, respectively; hupC encodes a membrane electron carrier protein which
      may be considered as the third subunit of the uptake hydrogenase. In Wolinella
      succinogenes, the hydC gene, homologous to hupC, has been shown to encode a low
      potential cytochrome b which mediates electron transfer from H2 to the quinone
      pool of the bacterial membrane. In whole cells of R. capsulatus or intact
      membrane preparation of the wild type strain B10, methylene blue but not benzyl
      viologen can be used as acceptor of the electrons donated by H2 to hydrogenase;
      on the other hand, membranes of B10 treated with Triton X-100 or whole cells of a
      HupC- mutant exhibit both benzyl viologen and methylene blue reductase
      activities. We report the effect of diphenylene iodonium (Ph2I), a known
      inhibitor of mitochondrial complex I and of various monooxygenases on R.
      capsulatus hydrogenase activity. With H2 as electron donor, Ph2I inhibited
      partially the methylene blue reductase activity in an uncompetitive manner, and
      totally benzyl viologen reductase activity in a competitive manner. Furthermore,
      with benzyl viologen as electron acceptor, Ph2I increased dramatically the
      observed lagtime for dye reduction. These results suggest that two different
      sites exist on the electron donor side of the membrane-bound [NiFe] hydrogenase
      of R. capsulatus, both located on the small subunit. A low redox potential site
      which reduces benzyl viologen, binds Ph2I and could be located on the distal
      [Fe4S4] cluster. A higher redox potential site which can reduce methylene blue in
      vitro could be connected to the high potential [Fe3S4] cluster and freely
      accessible from the periplasm.

PMID- 10924911
TI  - Conformational relaxation following reduction of the photoactive
      bacteriopheophytin in reaction centers from Balstochloris viridis. Influence of
      mutations at position M208.
AB  - The photochemically trapped bacteriopheophytin (BPh) b radical anion in the
      active branch (phi(*-)A) of reaction centers (RCs) from Blastochloris (formerly
      called Rhodopseudomonas) viridis is characterized by 1H-ENDOR as well as optical
      absorption spectroscopy. The two site-directed mutants YF(M208) and YL(M208), in
      which tyrosine at position M208 is replaced by phenylalanine and leucine,
      respectively, are investigated and compared with the wild type. The residue at
      M208 is in close proximity to the primary electron donor, P, the monomeric
      bacteriochlorophyll (BCh1), B(A), and the BPh, phiA, that are involved in the
      transmembrane electron transfer to the quinone, Q(A), in the RC. The analysis of
      the ENDOR spectra of (phi(*-)A at 160 K indicates that two distinct states of
      phi(*-)A are present in the wild type and the mutant YF(M208). Based on a
      comparison with phi(*-)A in RCs of Rhodobacter sphaeroides the two states are
      interpreted as torsional isomers of the 3-acetyl group of phiA. Only one phi(*-)A
      state occurs in the mutant YL(M208). This effect of the leucine residue at
      position M208 is explained by steric hindrance that locks the acetyl group in one
      specific position. On the basis of these results, an interpretation of the
      optical absorption difference spectrum of the state phi(*-)AQ(*-)A is attempted.
      This state can be accumulated at 100 K and undergoes an irreversible change
      between 100 and 200 K [Tiede et al., Biochim. Biophys. Acta 892 (1987) 294-302].
      The corresponding absorbance changes in the BCh1 Q(x) and Q(y) regions observed
      in the wild type also occur in the YF(M208) mutant but not in YL(M208). The
      observed changes in the wild type and YF(M208) are assigned to RCs in which the 3
      acetyl group of phiA changes its orientation. It is concluded that this distinct
      structural relaxation of phiA can significantly affect the optical properties of
      B(A) and contribute to the light-induced absorption difference spectra.

PMID- 10924910
TI  - Comparative study on uncoupling effects of laurate and lauryl sulfate on rat
      liver and skeletal muscle mitochondria.
AB  - Uncoupling effects of laurate and lauryl sulfate have been studied in the
      isolated rat liver and skeletal muscle mitochondria. In the oligomycin-treated
      liver mitochondria, 0.02 mM laurate or 0.16 mM lauryl sulfate caused a two-fold
      stimulation of respiration, accompanied by a membrane potential decrease.
      Carboxyatractylate (CAtr) and glutamate (or aspartate) strongly decrease the
      effect of laurate and lauryl sulfate on respiratory rate and membrane potential
      (the recoupling effect). With both uncouplers, this effect is maximal for CAtr
      and glutamate (aspartate) at pH 7.8 and 7.0, respectively. Tetraphenyl
      phosphonium cations, which decrease negative membrane charges, cause an alkaline
      shift of these pH dependences. Small amounts of lauryl sulfate, which increase
      the membrane negative charge, induce the opposite shift when laurate is used as
      an uncoupler. ADP, but not GDP, partially recouple with both laurate and lauryl
      sulfate. We conclude that lauryl sulfate-induced uncoupling in rat liver, like
      the uncoupling induced by laurate, is mediated by the ATP/ ADP and
      glutamate/aspartate antiporters. In skeletal muscle mitochondria uncoupled by
      laurate, 200 microM GDP causes partial recoupling which can be enhanced by a
      subsequent additions of CAtr, glutamate and serum albumin. CAtr added before GDP
      promotes a larger recoupling than when added after GDP and prevents the
      subsequent effect of GDP. ADP is effective as recoupler at lower concentrations
      that GDP, whereas CDP is without influence. Lauryl sulfate uncoupling of skeletal
      muscle mitochondria is GDP-resistant but is sensitive to ADP, CAtr, glutamate and
      serum albumin. Our data suggest that in skeletal muscle mitochondria a GDP
      sensitive mechanism is involved in uncoupling induced by laurate. This mechanism
      is absent in liver mitochondria. Possible mechanisms of laurate and lauryl
      sulfate-induced uncoupling are discussed.

PMID- 10924912
TI  - Covalent modification of the catalytic sites of the H+-ATPase from chloroplasts
      and 2-nitreno-ADP. Modification of the catalytic site 1 (tight) and catalytic
      sites 1 and 2 together impairs both uni-site and multi-site catalysis of ATP
      synthesis and ATP hydrolysis.
AB  - After isolation and purification, the H+-ATPase from chloroplasts, CF0F1,
      contains one endogenous ADP at a catalytic site, and two endogenous ATP at non
      catalytic sites. Incubation with 2-azido-[alpha-32P]ADP leads to tight binding of
      azidonucleotides. Free nucleotides were removed by three consecutive passages
      through centrifugation columns, and upon UV-irradiation most of the label was
      covalently bound. The labelled enzyme was digested by trypsin, the peptides were
      separated by ion exchange chromatography into nitreno-AMP, nitreno-ADP and
      nitreno-ATP labelled peptides, and these were then separated by reversed phase
      chromatography. Amino acid sequence analysis was used to identify the type of the
      nucleotide binding site. After incubation with 2-azido-[alpha-32P]ADP, the
      covalently bound label was found exclusively at beta-Tyr-362. Incubation
      conditions with 2-azido-[alpha-32P]ADP were varied, and conditions were found
      which allow selective binding of the label to different catalytic sites,
      designated as 1, 2 and 3 in order of decreasing affinity for ADP, and either
      catalytic site 1 or catalytic sites 1 and 2 together were labelled. For
      measurements of the degree of inhibition by covalent modification, CF0F1 was
      reconstituted into phosphatidylcholine liposomes, and the membranes were
      energised by an acid-base transition in the presence of a K+/valinomycin
      diffusion potential. The rate of ATP synthesis was 50-80 s(-1), and the rate of
      ATP hydrolysis was 15 s(-1) measured under multi-site conditions. Covalent
      modification of either catalytic site 1 or catalytic sites 1 and 2 together
      inhibited ATP synthesis and ATP hydrolysis equally, the degree of inhibition
      being proportional to the degree of modification. Extrapolation to complete
      inhibition indicates that derivatisation of catalytic site 1 leads to complete
      inhibition when 1 mol 2-nitreno-ADP is bound per mol CF0F1. Derivatisation of
      catalytic sites 1 and 2 together extrapolates to complete inhibition when 2 mol 2
      nitreno-ADP are bound per CF0F1. The rate of ATP synthesis and the rate of ATP
      hydrolysis were measured as a function of the substrate concentration from multi
      site to uni-site conditions with derivatised CF0F1 and with non-derivatised
      CF0F1. ATP synthesis and ATP hydrolysis under uni-site and under multi-site
      condition were inhibited by covalent modification of either catalytic site 1 or
      catalytic sites 1 and 2 together. The results indicate that derivatisation of
      site 1 inhibits activation of the enzyme and that cooperative interactions occur
      at least between the catalytic sites 2 and 3.

PMID- 10924913
TI  - A new microsystem for automated electrorotation measurements using laser
      tweezers.
AB  - We have developed a new microsystem for fast, automated studies of reactions and
      kinetics of single cells with biochemical or pharmacological agents. A cell spins
      in an external rotating electric field and the frequency dependence characterises
      the passive dielectric properties of membrane and cytoplasm. We use a planar
      microelectrode chip with microchannel (easily covered with a removable slip) for
      the application of frequencies exceeding 250 MHz to determine cytoplasmic
      properties in low and high conductivity electrolyte solutions. The laser tweezers
      serve as a bearing system, rotation is induced by microelectrodes and rotation
      speed is recorded automatically. This opens up new possibilities in
      biotechnology, e.g. for drug screening as demonstrated by measuring the influence
      of ionomycin on the passive dielectric properties of T-lymphoma cells.
      Additionally, a possible infrared-induced long-term cell damage could be observed
      by electrorotation and is discussed.

PMID- 10924914
TI  - Biophysical and structural characterization of proton-translocating NADH
      dehydrogenase (complex I) from the strictly aerobic yeast Yarrowia lipolytica.
AB  - Mitochondrial proton-translocating NADH-dehydrogenase (complex I) is one of the
      largest and most complicated membrane bound protein complexes. Despite its
      central role in eukaryotic oxidative phosphorylation and its involvement in a
      broad range of human disorders, little is known about its structure and function.
      Therefore, we have started to use the powerful genetic tools available for the
      strictly aerobic yeast Yarrowia lipolytica to study this respiratory chain
      enzyme. To establish Y. lipolytica as a model system for complex I, we purified
      and characterized the multisubunit enzyme from Y lipolytica and sequenced the
      nuclear genes coding for the seven central subunits of its peripheral part.
      Complex I from Y lipolytica is quite stable and could be isolated in a highly
      pure and monodisperse state. One binuclear and four tetranuclear iron-sulfur
      clusters, including N5, which was previously known only from mammalian
      mitochondria, were detected by EPR spectroscopy. Initial structural analysis by
      single particle electron microscopy in negative stain and ice shows complex I
      from Y. lipolytica as an L-shaped particle that does not exhibit a thin stalk
      between the peripheral and the membrane parts that has been observed in other
      systems.

PMID- 10924915
TI  - The inhibition of flavoproteins by phenoxaiodonium, a new iodonium analogue.
AB  - Iodonium compounds, especially diphenylene iodonium and iodonium diphenyl are
      used extensively as inhibitors of NADH-ubiquinone reductase and NADPH oxidase
      activity. Here, the use of a new iodonium compound, phenoxaiodonium is reported.
      The IC(50) of neutrophil superoxide production, measured using the superoxide
      dismutase inhibitable rate of cytochrome c reduction, was approximately 0.75
      microM, while 50% inhibition of mitochondrial respiration, measured by the rate
      of oxygen uptake using a Clark type oxygen electrode, was at approximately 20
      microM. The inhibition of oxidation of xanthine to urate by xanthine oxidase was
      also studied, giving a K(i) of 0.2 microM. Inhibition of nitric oxidase synthase
      (NOS: from rat brain) by 0.2 microM phenoxaiodonium was equivalent to 1 mM N(G)
      nitro-L-arginine methyl ester HCl (L-NAME), that is total abolition of activity.
      We conclude that phenoxaiodonium is an extremely good inhibitor of flavo-enzymes,
      but like diphenylene iodonium and iodonium diphenyl, will be of limited use as a
      pharmacological tool for the elucidation of the involvement of such enzymes in
      specific cellular functions.

PMID- 10924916
TI  - Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and
      palmitoylethanolamide.
AB  - We have investigated the inhibition of lipopolysaccharide stimulated nitric oxide
      production in RAW264.7 macrophages by the cannabinoids and the putative
      cannabinoid CB(2)-like receptor ligand, palmitoylethanolamide. (R)-(+)-[2, 3
      dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo-[1,2,3-de]-1, 4-benzoxazin-6-yl]
      1-naphthalenylmethanone mesylate ((+)-WIN55212) and, to a lesser extent (-)-cis-3
      [2-hydroxy-4-(1, 1-dimethylheptyl)phenyl]-trans-4-(3-hydroxy-propyl)cyclohexan++
      +-1-ol (CP55940), significantly inhibited lipopolysaccharide stimulated nitric
      oxide production. The level of inhibition was found to be dependent on the
      concentration of lipopolysaccharide used to induce nitric oxide production.
      Palmitoylethanolamide significantly inhibited nitric oxide production induced by
      lipopolysaccharide. The inhibition of nitric oxide production by (+)-WIN55212 but
      not palmitoylethanolamide was significantly attenuated in the presence of the
      cannabinoid CB(2) receptor antagonist, N-[(1S)-endo-1,3, 3-trimethyl bicyclo
      [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3
      carboxamide (SR144528). (+)-WIN55212 produced a pertussis toxin-sensitive
      parallel rightward shift in the log concentration-response curve for
      lipopolysaccharide, causing a fivefold increase in the EC(50) value for
      lipopolysaccharide with no change in the E(max) value. (-)-WIN55212 had no effect
      on the log concentration-response curve for lipopolysaccharide.
      Palmitoylethanolamide did not produce a rightward shift in the lipopolysaccharide
      concentration-response curve. However, it did produce a pertussis toxin
      insensitive reduction in the E(max) value. The results suggest that the
      inhibition of lipopolysaccharide mediated nitric oxide release by (+)-WIN55212 in
      murine macrophages is mediated by cannabinoid CB(2) receptors. In contrast, the
      inhibition by palmitoylethanolamide does not appear to be mediated by cannabinoid
      receptors.

PMID- 10924917
TI  - Effects of RPR 118723, a novel antagonist at the glycine site of the NMDA
      receptor, in vitro.
AB  - RPR 118723 ((8-chloro-5-methyl-2,3-dioxo-1,4-dihydro-5H-indeno[1, 2-b]pyrazin-5
      yl) acetic acid) was previously reported to exhibit potent affinity for the
      glycine site of the N-methyl-D-aspartate (NMDA) receptor-channel complex in the
      nanomolar range (K(i)=3.1+/-0. 8 nM). We now report on the effects of RPR 118723
      in two functional tests reflecting the interaction between the glycine site and
      the NMDA receptor. First, RPR 118723 potently inhibited [3H]N-[1-(2
      thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in the presence of NMDA
      (IC(50)=3.5+/-0.4 nM). Second, RPR 118723 antagonized the NMDA-induced increase
      in [3H]dopamine release in mouse striatal slices (IC(50)=8.0+/-1.1 nM). In both
      experimental models, an excess of glycine reversed the effect of RPR 118723.
      These results show that RPR 118723 interferes functionally in the nanomolar range
      with the glycine site coupled to the NMDA receptor in vitro. The blockade of the
      glycine site with RPR 118723 may be useful for the therapy of the disorders
      linked to excessive NMDA stimulation.

PMID- 10924918
TI  - Low-affinity block of cardiac K(+) currents by nifedipine.
AB  - Nifedipine inhibits a variety of K(+) currents with IC(50) between 4 and 40
      microM. Among the more sensitive of these are two types (transient outward and
      ultrarapid hKv1.5) found in the heart. To evaluate the actions of the drug on
      other prominent cardiac K(+) currents, guinea-pig ventricular myocytes were
      voltage-clamped for measurement of inwardly rectifying K(+) current (I(K1)),
      rapidly activating delayed-rectifier K(+) current (I(Kr)), and slowly activating
      delayed-rectifier K(+) current (I(Ks)). The currents were unaffected by < or =10
      microM nifedipine, but inhibited by higher concentrations; IC(50) values were 260
      microM for I(K1), 275 microM for I(Kr), and 360 microM for I(Ks). The time- and
      voltage-dependent properties of I(Ks) were unaffected by the drug, and full block
      was attained on the first depolarisation after a rest. The results establish that
      the sensitivity of I(Kr) and I(Ks) to inhibition by nifedipine is approximately
      50 times lower than the sensitivity of other cardiac delayed-rectifier K(+)
      currents.

PMID- 10924919
TI  - (S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxide: (S18986-1)
      a positive modulator of AMPA receptors enhances (S)-AMPA-mediated
      [3H]noradrenaline release from rat hippocampal and frontal cortex slices.
AB  - The present study describes the effect of (S)-2,3-dihydro-[3, 4]cyclopentano
      1,2,4-benzothiadiazine-1,1-dioxide (S18986-1), a positive allosteric modulator of
      the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors
      with cognitive-enhancing effects, on (S)-AMPA-induced [3H]noradrenaline release
      in rat hippocampal and frontal cortex slices. (S)-AMPA significantly increased
      [3H]noradrenaline release in rat hippocampus and frontal cortex slices, whereas
      S18986-1 (3-1000 microM) alone, was inactive. However, S18986-1 between 30 and
      1000 microM potently enhanced (+200%) (S)-AMPA-mediated [3H]noradrenaline release
      in both hippocampal and frontal cortex slices. The capacity of S18986-1 to
      potentiate [3H]noradrenaline release was specific for AMPA receptors as S18986-1
      failed to potentiate either kainate and N-methyl-D-aspartate (NMDA)-mediated
      release of [3H]noradrenaline in rat hippocampal slices. Moreover, 1, 2,3,4
      tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) and 1-(4
      aminophenyl)-3-methylcarbamoyl-4-methyl-3, 4-dihydro-7,8-methylenedioxy-5H-2,3
      benzodiazepine (GYKI-53655) but not (5R,10S)-(+)-5-methyl-10,11-dihydro-5H
      dibenzo[a,d]cyclohepten-5, 10-imine ((+)-MK-801), inhibited (S)-AMPA and S18986
      induced stimulation of (S)-AMPA-mediated [3H]noradrenaline release. In addition,
      S18986-1-induced stimulation of (S)-AMPA-evoked [3H]noradrenaline release was
      markedly attenuated in the presence of tetrodotoxin (1 microM) and in Ca(2+)-free
      buffer. S18986-1 enhanced (S)-AMPA-mediated [3H]noradrenaline release to a
      greater extent than its corresponding (R)-enantiomer S19024-1 and racemic mixture
      S17951-1. However, positive allosteric modulators of AMPA receptors such as
      aniracetam failed to potentiate AMPA-mediated noradrenaline release in
      hippocampal slices, whereas cyclothiazide potently enhanced (S)-AMPA-mediated
      [3H]noradrenaline release. These results suggest that the capacity of S18986-1 to
      enhance AMPA receptor-mediated release of noradrenaline in rat hippocampus and
      frontal cortex, could contribute to the cognition enhancing mechanisms of S18986
      1.

PMID- 10924920
TI  - Correlation between neuroleptic binding to sigma(1) and sigma(2) receptors and
      acute dystonic reactions.
AB  - Acute dystonic reactions are motor side effects that occur soon after the
      initiation of neuroleptic treatment. Although earlier studies indicate that these
      abnormal movements can be induced in animals and humans via activation of sigma
      receptors, the relative contribution of the different sigma receptor subtypes is
      unknown. Since sigma(1) and sigma(2) receptor are differentially represented in
      motor regions of the brain, the affinities of 17 neuroleptics for these sigma
      receptor subtypes were determined using competition binding studies. The results
      revealed that most neuroleptics do not exhibit selectivity for either of the
      sigma receptor subtypes, as reflected by a significant correlation between the
      affinities of the neuroleptics for sigma(1) vs. sigma(2) receptors. Moreover,
      when the sigma binding affinities of the neuroleptics were correlated with the
      tendency of the drugs to produce acute dystonic reactions in humans, there was a
      significant correlation for both subtypes. Together with earlier studies in
      animals, the data suggest that neuroleptic-induced motor side effects can be
      mediated through both sigma(1) and sigma(2) receptors.

PMID- 10924921
TI  - Blockade of lipopolysaccharide-induced fever by a mu-opioid receptor-selective
      antagonist in rats.
AB  - The endogenous opioid system has been found to be involved in fever caused by
      pyrogens. In the present study, we have investigated the role of the mu-opioid
      receptor in the brain in fever induced by lipopolysaccharide. Rats were
      microinjected with 1 microg of the mu-opioid receptor-selective antagonist,
      cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), into the preoptic
      anterior hypothalamus. Thirty minutes later, lipopolysaccharide (50 microg/kg)
      was injected intraperitoneally (i.p.). CTAP reduced by 1 degrees C the fever
      induced by lipopolysaccharide. However, it did not affect lipopolysaccharide
      fever when it was given 3 h after lipopolysaccharide injection. These data
      indicate that mu-opioid receptors within the preoptic anterior hypothalamus
      mediate the initiation of lipopolysaccharide fever and suggest that the opioid
      system is involved in the pathogenesis of fever in rats.

PMID- 10924922
TI  - Vigabatrin reduces epileptiform activity in brain slices from pharmacoresistant
      epilepsy patients.
AB  - Human neocortical temporal lobe tissue resected for treatment of
      pharmacoresistant epilepsy was investigated. In slices prepared from this tissue,
      epileptiform field potentials (EFP) were induced by omission of magnesium from
      the artificial cerebrospinal fluid (ACSF). The effects of the gamma-aminobutyric
      acid transaminase inhibitor vigabatrin on EFP were tested. Vigabatrin exerted a
      dose-dependent reduction of the repetition rate of EFP: after 3 h of
      administration of vigabatrin in concentrations of 100 and 200 micromol/l, the
      repetition rate of EFP was reduced to 35% and 18% of the initial values,
      respectively. This effect was not reversible. In control experiments with
      neocortical slices from rats, vigabatrin reduced EFP in a comparable range. The
      results demonstrate a strong antiepileptic effect of vigabatrin on EFP in tissues
      from pharmacoresistant epilepsy patients.

PMID- 10924923
TI  - Mediation of ionotropic glutamate receptors in domoic acid-induced striatal
      dopamine release in rats.
AB  - Our objective was to characterize the mechanism of action of intrastriatal
      infusion of domoic acid on extracellular dopamine levels, using in vivo dialysis
      in conscious and freely moving rats. The local infusion of domoic acid (500
      microM) caused an increase (567.9+/-142.5%, versus basal) in dopamine
      extracellular levels associated with a decrease in its metabolites:
      dihydroxyphenylacetate (DOPAC) and homovanillate (HVA) (47.3+/-4.4% and 33.8+/
      4.2%, respectively, compared to basal). Infusion of the amino-3-hydroxy-5-methyl
      4-isoxazolepropionic acid/kainate (AMPA/kainate) receptor antagonist, 6,7
      dinitroquinoxaline-2,3-dione (DNQX; 200 microM) reversed the effect of domoic
      acid infusion on striatal dopamine levels. However, the infusion of the selective
      non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, dizocilpine (MK
      801; 50 microM), did not change significantly the effect of domoic acid on
      dopamine extracellular levels. In conclusion, based on results with a
      microdialysis technique, we suggest that domoic acid may act through AMPA/kainate
      receptors in striatum.

PMID- 10924924
TI  - Cannabinoid CB(1) receptor agonists increase rat cortical and hippocampal
      acetylcholine release in vivo.
AB  - Intravenous administration of the cannabinoid CB(1) receptor agonists (R-(+)-[2,
      3-Dihydro-5-methyl-3[morpholinyl)methyl]-pyrrolo[1,2,3-de]-1, 4-benzoxazinyl]-(1
      naphthalenyl)methanone mesylate), WIN 55,212-2 (10, 37.5, 75 and 150 microg/kg),
      and ((6aR)-trans-3-(1, 1-Dimethylheptyl)-6a,7,10,10a-tetrahydro-1-hydroxy-6, 6
      dimethyl-6H-dibenzo[b,d]pyran-9-methanol), HU 210 (1 and 4 microg/kg) dose
      dependently increased acetylcholine release in dialysates from the prefrontal
      cortex and the hippocampus of freely moving rats. Administration of the
      cannabinoid receptor antagonist [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4
      dichlorophenyl)-4-methyl-1H-pyrazole-3 carboxamide]HCl, SR 141716A, at a dose
      that per se did not affect basal acetylcholine release (2. 5 microg/kg),
      prevented the increase of acetylcholine release by WIN 55,212-2 (150 microg/kg
      i.v.) or by HU 210 (4 microg/kg i.v.) in both areas. These data demonstrate that,
      at low i.v. doses, the synthetic cannabinoid CB(1) receptor agonists, WIN 55,212
      2 and HU 210 stimulate cortical and hippocampal acetylcholine release.

PMID- 10924925
TI  - Up-regulation of the TrkB receptor in mice injured by the partial ligation of the
      sciatic nerve.
AB  - Partial nerve injury induced by tying a tight ligature around the sciatic nerve
      induced a marked hyperalgesia, and this persistent painful state lasted for 14
      days in mice. Under these conditions, the nerve injury induced a significant
      increase in protein level of protein kinase Cgamma isoform in plasma membranes in
      the spinal cord. We report here for the first time that protein level of TrkB
      receptor located in plasma membranes was clearly up-regulated in the spinal cord
      obtained from the nerve-injured mice. These findings suggest that the up
      regulation of protein kinase Cgamma associated with activated TrkB receptors
      following partial sciatic nerve ligation may induce sensitization of synaptic
      transmission and may in turn cause the persistent pain in mice.

PMID- 10924926
TI  - Implications of the NR2B subunit-containing NMDA receptor localized in mouse
      limbic forebrain in ethanol dependence.
AB  - The present study was designed to further investigate the direct involvement of
      the NR2B-containing NMDA receptor in ethanol dependence. Using the liquid diet
      method, mice were chronically treated with skimmed milk containing 5% ethanol for
      5 days. After the discontinuation of ethanol, mice revealed tremor, handling
      elicited convulsion and death. Treatment with a selective NR2B-containing NMDA
      receptor antagonist, ifenprodil, significantly suppressed the expression of
      ethanol withdrawal signs. The protein level of NR2B subunits in the limbic
      forebrain, but not the cerebral cortex, during chronic ethanol treatment was
      markedly increased with respect to the levels in control mice. The significant up
      regulation of NR2B subunits lasted for at least 9 h after the discontinuation of
      ethanol and returned to the basal level by 48 h after the withdrawal. These
      findings suggest that the up-regulation of NR2B subunits during chronic ethanol
      exposure may be implicated in the initial development of physical dependence on
      ethanol.

PMID- 10924927
TI  - Analgesic doses of the enkephalin degrading enzyme inhibitor RB 120 do not have
      discriminative stimulus properties.
AB  - The systemically active mixed inhibitor of enkephalin metabolism, N-((S)-2-benzyl
      3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB
      120), alone or in combination with 4-?[2-[[3-(1H-indol-3-yl))-2-methyl-1-oxo-2
      [[(tricyclo[3.3.1.1. ]dec-2-yloxy) carbonyl]amino?propyl]amino]-1
      phenylethyl]amino?-4-oxo-[R-(R*, R*)]-butanoate N-methyl-D-glucamine (CI 988;
      CCK(1) receptor antagonist) was investigated for discriminative and morphine
      generalisation effects using an operant drug discrimination paradigm in rats.
      Animals dosed with RB 120 (10 mg/kg) failed to develop a discriminative response.
      Combined CI 988 (0.3 mg/kg) and RB 120 (10 mg/kg) also failed to elicit a
      discriminative response. Morphine-trained animals (3.0 mg/kg) did not generalise
      to RB 120 (10 and 20 mg/kg). Similarly, subsequent retraining of the same animals
      with 1.5 mg/kg of morphine did not elicit generalisation to RB 120 (10 or 20
      mg/kg). Combined RB 120 (10 or 20 mg/kg) and CI 988 (0.3 or 3.0 mg/kg) treatment
      produced no notable drug lever selection in rats able to discriminate morphine
      (1.5 mg/kg) from saline. These results suggest that RB 120 may have low abuse
      potential at analgesic doses.

PMID- 10924928
TI  - Effects of S 18986-1, a novel cognitive enhancer, on memory performances in an
      object recognition task in rats.
AB  - (S)-2,3-dihydro-[3,4]cyclopentano-1,2,4-benzothiadiazine-1,1-dioxi de (S 18986-1)
      is a new compound that facilitates post-synaptic responses by modulating alpha
      amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated
      synaptic responses and thus promotes long-term potentiation and potentiates (S)
      AMPA-induced release of noradrenaline in rat brain slices. In the present study,
      the effects of S 18986-1 were evaluated on cognitive functions by using a one
      trial object-recognition test in the Wistar rat, a test which measures a form of
      episodic memory in rodents. Recognition was measured by the ability of treated
      rats to discriminate between a familiar and a new object after a 24-h retention
      delay. Oral administrations with S 18986-1 (0.3 to 100 mg/kg) 1 h before each
      session of the test improved object recognition at concentrations as low as 0.3
      mg/kg. Under the same conditions, the nootropic drug aniracetam was active at a
      dose of 10 mg/kg by i.p. route. S 18986-1 was still effective on the object
      recognition test when it was administered 4 h before each of the three sessions.
      Furthermore, subchronic oral pretreatment (7 days) with S 18986-1 (0.3 to 30
      mg/kg) also increased the recognition of the familiar object indicating that the
      animals failed to develop tolerance to repeated administrations with S 18986-1.
      Finally, the recognition of the familiar object was improved when S 18986-1 was
      administered before the recognition trial whereas the rats failed to recognise
      the familiar object when S 18986-1 was administered before the sample
      presentation trial only. Taken together, the results indicated that S 18986-1
      facilitated a form of episodic memory in the rat, by improving the recognition of
      a familiar information (retention). Furthermore, S 18986-1 was long-acting and
      demonstrated a good oral bioavailability. These data confer on S 18986-1, a
      potential role in improving episodic memory impaired in neurodegenerative
      diseases and during aging.

PMID- 10924929
TI  - Hypocapnic constriction in rabbit basilar artery in vitro: triggering by N(G)
      monomethyl-L-arginine monoacetate and dependence on endothelin-1 and alkalosis.
AB  - This study tested whether hypocapnic constriction of the rabbit basilar artery in
      vitro can be triggered by a nitric oxide (NO) synthase inhibitor, and whether the
      resulting constriction is (1) due to the alkaline pH associated with hypocapnia,
      and (2) endothelin-1 mediated. Hypocapnic (25 mM NaHCO(3); pH 7.76; pCO(2) 14.2)
      or isocapnic alkaline solution (50 mM NaHCO(3); pH 7.73; pCO(2) 35.0) rarely
      altered basal tension. N(G)-monomethyl-L-arginine monoacetate (L-NMMA; 0.1 mM)
      challenge in hypocapnic or isocapnic alkaline solution resulted in near maximal
      tension that was maintained for 2-2.5 h even following L-NMMA washout. L-NMMA
      challenge in normal solution (25 mM NaHCO(3); pH 7. 42; pCO(2) 36.9) also induced
      near maximal tension, although the tension was maintained for only 25 min (mean).
      Ac-D-Bhg-L-Leu-Asp-L-Ile-L-Ile-L-Trp (PD145065), homopiperidinyl-CO-Leu-D
      Trp(CHO)-D-Trp (BQ610), and N-cis-2, 6-dimethyl-piperidinocarbonyl L-gamma-MeLeu
      D-Trp (COOCH(3))-Nle (BQ788; 1-3 microM), endothelin ET(A)/ET(B), endothelin
      ET(A), and endothelin ET(B) receptor antagonists, respectively, completely
      relaxed the tension that resulted from L-NMMA challenge in hypocapnic or
      isocapnic alkaline solution. These results demonstrate that constriction due to
      hypocapnia in vitro can be triggered by an NO synthase inhibitor and is
      endothelin-1 mediated. Additionally, alkaline pH in the absence of decreased
      pCO(2) is sufficient to elicit the constriction.

PMID- 10924931
TI  - Dexfenfluramine-induced contraction of human and rat isolated pulmonary arteries.
AB  - Mechanisms of dexfenfluramine-induced vasoconstriction were studied in isolated
      pulmonary arteries suspended in organ baths for isometric tension recording.
      Dexfenfluramine (10(-7)-10(-4) M) caused concentration-dependent contractions in
      rat and human pulmonary arteries with and without endothelium. In pulmonary
      arteries of the rat, the response to dexfenfluramine was nearly abolished by
      treatment with the alpha-adrenoceptor antagonists, phentolamine (10(-6) M) or
      prazosin (10(-7) M). In human pulmonary arteries, the concentration-response
      curve to dexfenfluramine was unaltered by the presence of phentolamine (10(-6)
      M), prazosin (10(-7) M), ketanserin (10(-6) M), or indomethacin (3x10(-6) M). The
      results suggest that dexfenfluramine causes contraction of pulmonary vascular
      smooth muscle by multiple mechanisms, one of which involves activation of alpha
      adrenoceptors within the blood vessel wall. The mechanisms by which
      dexfenfluramine causes pulmonary vasoconstriction may differ between rat and
      human pulmonary arteries.

PMID- 10924930
TI  - Mesenteric vasoconstrictor response to 5-hydroxytryptamine in the in situ blood
      autoperfused rat mesentery: involvement of 5-HT(2B) and/or 5-HT(2C) receptor
      activation.
AB  - Using a number of agonist and antagonist compounds, we attempted to characterize
      the responses and receptors involved in the effects of 5-hydroxytryptamine (5-HT)
      in the in situ blood perfused rat mesentery. An intra-arterial (i.a.) bolus
      injection of 5-HT increased mesenteric perfusion pressure in a dose-dependent way
      but did not change the systemic blood pressure. The selective 5-HT(2) receptor
      agonists alpha-methyl-5-HT, 1-(3-chlorophenyl)piperazine dihydrochloride (m-CPP)
      and (+/-)-1-(4-iodo-2, 5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI),
      caused a local vasoconstrictor effect in the autoperfused vascular mesenteric
      bed. Intra-arterial injection of 5-carboxamidotryptamine (5-CT) and 1-(m
      chlorophenyl)-biguanide (m-CPBG) did not modify the mesenteric perfusion
      pressure. The vasoconstrictor effect elicited by 5-HT and alpha-methyl-5-HT was
      significantly decreased by ritanserin and by a selective 5-HT(2B/2C) receptor
      antagonist, N-3-pyridinyl-3, 5-dihydro-5-methyl-benzo[1,2-b:4,5-b']dipyrrole
      1(2H)-carboxamide hydrochloride (SB 206553), but was not modified by prazosin,
      propranolol, indomethacin or enalapril pretreatment. Our data suggest that the
      vasoconstrictor serotonergic response induced in the in situ autoperfused rat
      mesenteric vascular bed is mainly mediated by activation of 5-HT(2B) and/or 5
      HT(2C) receptors.

PMID- 10924932
TI  - Possible site of action of TAK-637, a tachykinin NK(1) receptor antagonist, on
      the micturition reflex in guinea pigs.
AB  - TAK-637((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8,9,10, 11-tetrahydro-9-methyl
      5-(4-methylphenyl)-7H-[1,4]diazocino[2,1-g] [1,7]naphthyridine-6,13-dione) is a
      novel tachykinin NK(1) receptor antagonist that has been shown to inhibit the
      micturition reflex in guinea pigs. The aim of this study was to clarify its
      mechanism of action in guinea pigs. TAK-637 inhibited the spinal vesico-vesical
      reflex induced by electrical stimulation of the proximal cut end of the pelvic
      nerve in spinal animals, but not bladder contractions induced by electrical
      stimulation of the distal cut end of the nerve. Furthermore, TAK-637 had no
      effect on carbachol- or electrical field stimulation-induced contractions of
      isolated bladder muscle strips in an organ bath, whereas drugs used for
      abnormally frequent micturition inhibited both contractions. These results
      suggest that TAK-637 inhibits the micturition reflex by acting, at least in part,
      on the spinal cord, and its mechanism of action clearly differs from those of
      antimuscarinics or spasmolytics.

PMID- 10924934
TI  - Altered non-adrenergic non-cholinergic neurotransmission in gastric fundus from
      streptozotocin-diabetic rats.
AB  - The influence of streptozotocin-induced diabetes has been investigated on
      responses to non-adrenergic, non-cholinergic (NANC) nerve stimulation in rat
      gastric fundus. NANC relaxations in precontracted muscle strips from diabetic
      rats were smaller than those from control rats. In addition, the relaxations in
      diabetic but not control rats were followed by rapidly-developing frequency
      dependent contractions. In the presence of alpha-chymotrypsin and N(G)-nitro-L
      arginine methyl ester (L-NAME), the NANC contractions were markedly enhanced in
      diabetic rats. Treatment with the aldose reductase inhibitor, sorbinil, did not
      affect NANC relaxations or contractions in tissues from diabetic rats, and
      responses remained significantly different from those from control rats. The
      findings suggest that diabetes impairs relaxations to NANC nerve stimulation in
      the rat gastric fundus, and that a contractile NANC neurotransmitter(s) is
      released in diabetic rats. The results also suggest that diabetes-induced
      alterations in the NANC nerve response are not caused by increased activity of
      the aldose reductase pathway.

PMID- 10924933
TI  - Nitric oxide-induced cGMP accumulation in the mouse bladder is not related to
      smooth muscle relaxation.
AB  - The functional role of nitric oxide (NO) and the guanylate cyclase/cGMP second
      messenger system was investigated in the mouse bladder. Electrical field
      stimulation and the NO-donor 3-morpholino-sydnonimin hydrochloride (SIN-1) did
      not induce relaxation of the carbachol-precontracted bladder. However, sodium
      nitroprusside (10(-3) M) was found to enhance the contractile response to
      electrical field stimulation by 24+/-6% (n=8; P<0.05) without affecting the
      contractile response to carbachol. The enhancement of bladder contractility
      evoked by sodium nitroprusside was inhibited by the guanylate cyclase inhibitor
      1H-[1,2, 4]oxadiazolo[4,3-a]quinoxalime-1-one (ODQ; 10(-6) M). Incubation of
      bladder strips with SIN-1 and sodium nitroprusside caused an increase in cGMP
      accumulation as measured by radioimmunoassay. Immunohistochemical studies showed
      cGMP-immunoreactivity in nerve fibres and in stromal cells, but not in smooth
      muscle bundles after exposure to NO-donors. The results show that NO-donors have
      no inhibitory effect on smooth muscle tone in the mouse bladder, but that NO may
      have a functional role as an excitatory neuromodulator. The targets of endogenous
      NO in the bladder may be the demonstrated cGMP-positive structures, i.e., nerves
      and stromal cells.

PMID- 10924935
TI  - A dendritic cable model for the amplification of synaptic potentials by an
      ensemble average of persistent sodium channels.
AB  - The persistent sodium current density (I(NaP)) at the soma measured with the
      'whole-cell' patch-clamp recording method is linearized about the resting state
      and used as a current source along the dendritic cable (depicting the spatial
      distribution of voltage-dependent persistent sodium ionic channels). This
      procedure allows time-dependent analytical solutions to be obtained for the
      membrane depolarization. Computer simulated response to a dendritic current
      injection in the form of synaptically-induced voltage change located at a
      distance from the recording site in a cable with unequally distributed persistent
      sodium ion channel densities per unit length of cable (the so-called 'hot-spots')
      is used to obtain conclusions on the density and distribution of persistent
      sodium ion channels. It is shown that the excitatory postsynaptic potentials
      (EPSPs) are amplified if hot-spots of persistent sodium ion channels are
      spatially distributed along the dendritic cable, with the local density of I(NaP)
      with respect to the recording site shown to specifically increase the peak
      amplitude of the EPSP for a proximally placed synaptic input, while the spatial
      distribution of I(NaP) serves to broaden the time course of the amplified EPSP.
      However, in the case of a distally positioned synaptic input, both local and
      nonlocal densities yield an approximately identical enhancement of EPSPs in
      contradiction to the computer simulations performed by Lipowsky et al. [J.
      Neurophysiol. 76 (1996) 2181]. The results indicate that persistent sodium
      channels produce EPSP amplification even when their distribution is relatively
      sparse (i.e. , approximately 1-2% of the transient sodium channels are found in
      dendrites of CA1 hippocampal pyramidal neurons). This gives a strong impetus for
      the use of the theory as a novel approach in the investigation of synaptic
      integration of signals in active dendrites represented as ionic cables.

PMID- 10924936
TI  - Theoretical analysis of the amplification of synaptic potentials by small
      clusters of persistent sodium channels in dendrites.
AB  - We extend on the work developed by R.R. Poznanski and J. Bell from a linearized
      somatic persistent sodium current source to a non-linear representation of the
      dendritic Na(+)P current source associated with a small number of persistent
      sodium channels. The main objective is to investigate the modulation in the
      amplification of excitatory postsynaptic potentials (EPSPs) in dendrites studded
      with persistent sodium channels. The relation between membrane potential (V) and
      persistent sodium current density (I(NaP)) is approximated heuristically with a
      sigmoidal function and the resultant cable equation is solved analytically using
      a regular perturbation expansion and Green's function techniques. The transient
      simulated (non-evoked) response is found as a result of current injection in the
      form of synaptically induced voltage change located at a distance from the
      recording site in a cable with a uniform distribution of ion channel densities
      per unit length of cable (the so-called 'hot-spots') and with the conductance of
      each hot-spot (i.e., number of channels per hot-spot) assumed to be a constant.
      The results show an amplification in the observed EPSPs to be compatible with the
      experimentally derived estimates, and in addition a saturation in the
      amplification is observed indicating an optimum number of ionic channels.

PMID- 10924937
TI  - A stochastic-covariate failure model with an application to case-control
      analysis.
AB  - A stochastic process X(t) is periodically stationary (and ergodic) if, for every
      k> or =1 and every (t(1),ellipsis,t(k)) in R(k), the sequence of random vectors
      (X(t(1)+n),ellipsis,X(t(k)+n))n=0,+1, ellipsis, is stationary (and ergodic). For
      such an ergodic process, let T be a positive random variable defined on the
      sample space of the process, representing a time of failure. The local failure
      rate function is assumed to be of the form up(x),-infinity<x<infinity, where p(x)
      is a non-negative continuous function, and u>0 is a small number, tending to 0;
      and, for each u,T=T(u) is the corresponding failure-time. It is shown that
      X(T(u)) and uT(u) have, for u-->0, a limiting joint distribution and are, in
      fact, asymptotically independent. The marginal distributions are explicitly
      given. Let Y be a random variable whose distribution is the limit of that of
      X(T(u)). Under the hypothesis that p(x) is unknown or of known functional form
      but with unknown parameters, it is shown how p(x) can be estimated on the basis
      of independent copies of the random variable Y. The results are applied to the
      analysis of a case-control study featuring a 'marker' process X(t) and an 'event
      time' T. The event in the study is considered to be particularly rare, and this
      is reflected in the assumption u-->0. The control-distribution is identified with
      the average marginal distribution of the (periodically stationary) marker process
      X(t), and the case-distribution is identified with that of Y. The particular
      application is a biomedical trial to determine the risk of stroke in terms of the
      level of an anticoagulant in the blood of the patient.

PMID- 10924938
TI  - Uniform persistence and permanence for non-autonomous semiflows in population
      biology.
AB  - Conditions are presented for uniform strong persistence of non-autonomous
      semiflows, taking uniform weak persistence for granted. Turning the idea of
      persistence upside down, conditions are derived for non-autonomous semiflows to
      be point-dissipative. These results are applied to time-heterogeneous models of S
      I-R-S type for the spread of infectious childhood diseases. If some of the
      parameter functions are asymptotically almost periodic, an almost sharp threshold
      result is obtained for uniform strong endemicity versus extinction in terms of
      asymptotic time averages. Applications are also presented to scalar retarded
      functional differential equations modeling one species population growth.

PMID- 10924939
TI  - Treatment of hypertension in black patients.

PMID- 10924941
TI  - Consensus conference on adjuvant and palliative treatment of colorectal cancer.
      Netherlands Society for Medical Oncology.

PMID- 10924940
TI  - Clinical significance of low cobalamin levels in older hospital patients.
AB  - BACKGROUND: It is still a commonly held belief that many of the frequently found
      low cobalamin (Cbl, vitamin B12) levels in older people do not represent
      deficiency and are therefore without clinical significance and should not be
      treated. In this study this notion will be challenged. METHODS: In this
      prospective observational cohort design we studied 28 patients aged 65 years and
      older with low plasma Cbl (< or =150 pmol/l). A number of haematological (Hb,
      MCV, five- and six-lobed granulocytes), metabolic (plasma levels of methylmalonic
      acid and homocysteine), and gastrointestinal (plasma pepsinogen A and C and
      protein-bound and free Cbl absorption) parameters, and the response to Cbl
      treatment, were measured. Cbl deficiency was considered to be present when at
      least one of the following three criteria was fulfilled: (1) haematological or
      metabolic abnormalities compatible with Cbl deficiency; (2) Cbl malabsorption or
      atrophic gastritis; (3) a response to Cbl supplementation. RESULTS:
      Haematological or metabolic abnormalities were identified in 27 patients.
      Atrophic gastritis and Cbl malabsorption were identified in, respectively, 15 and
      23 patients. Each treated patient showed a haematological or metabolic response
      to Cbl supplementation. All patients were considered Cbl deficient: 18 patients
      (64%) fulfilled three criteria of Cbl deficiency, eight (29%) fulfilled two
      criteria and two (7%) fulfilled one criterion. CONCLUSIONS: According to the
      generally accepted and a wide variety of criteria, we found that older patients
      with low Cbl levels were cobalamin deficient. Therefore, these patients should
      receive Cbl supplementation.

PMID- 10924942
TI  - Reversible renal failure after treatment with omeprazole.
AB  - Omeprazole is a proton pump inhibitor widely used in the treatment of gastro
      esophageal reflux disease and peptic ulcer disease. In a 73-year-old man we
      describe renal failure due to acute interstitial nephritis after use of omeprazol
      during 4 months. Unexpected renal failure without signs of hydronephrosis should
      always provoke awareness of drug reaction, omeprazole being one of the possible
      drugs.

PMID- 10924943
TI  - Subacute Budd-Chiari syndrome associated with polycythemia vera and factor V
      Leiden mutation.
AB  - We describe a 48-year-old caucasian woman with a subacute Budd-Chiari syndrome
      attributed to the presence of polycythaemia vera, heterozygosity for the factor V
      Leiden mutation and the use of an oral contraceptive pill. Two diagnostic
      pitfalls were encountered. First, on CT scanning of the abdomen the still
      normally vascularized central part of the liver was initially judged as a
      hypervascular tumour. Second, there was difficulty to recognize the
      thrombocytosis/leukocytosis in relation with portal hypertension and
      hypersplenism. Our case illustrates the obstacles which can be faced during the
      diagnostical process in a subacute form of Budd-Chiari syndrome. Furthermore, our
      case illustrates the need for routinely screening of the factor V Leiden mutation
      in patients with Budd-Chiari syndrome.

PMID- 10924945
TI  - Symposium 'Recent developments in hereditary Cancer' held in utrecht, february 4,
      2000 abstracts of the papers presented at the XIIIth symposium of the netherlands
      foundation for the detection of hereditary tumours

PMID- 10924944
TI  - Diuretic therapy in Afrocaribbeans with uncomplicated essential hypertension.

PMID- 10924946
TI  - Participation of hippocampal metabotropic glutamate receptors, protein kinase A
      and mitogen-activated protein kinases in memory retrieval.
AB  - The ability to recall past events is a major determinant of survival strategies
      in all species and is of paramount importance in determining our uniqueness as
      individuals. In contrast to memory formation, the information about the molecular
      mechanisms of memory retrieval is surprisingly scarce and fragmentary. Here we
      show that pretest inhibition of the specific upstream activator of mitogen
      activated protein kinase kinase, or of protein kinase A in the hippocampus,
      blocked retrieval of long-term memory for an inhibitory avoidance task, a
      hippocampal-dependent learning task. An activator of protein kinase A enhanced
      retrieval. Mitogen-activated protein kinase activation increased in the
      hippocampus during retrieval, while protein kinase A activity remained unchanged.
      Pretest intrahippocampal blockade of metabotropic glutamate receptors or alpha
      amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate receptors, but not
      N-methyl-D-aspartate receptors or calcium/calmodulin dependent-protein kinase II,
      impaired retrieval. Thus, recall of inhibitory avoidance activates mitogen
      activated protein kinase, which is necessary, along with metabotropic glutamate
      receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazolone propionic acid/kainate
      receptors, and protein kinase A, for long-term memory expression. Our results
      indicate that memory formation and retrieval may share some molecular mechanisms
      in the hippocampus.

PMID- 10924947
TI  - Exploration of a novel environment leads to the expression of inducible
      transcription factors in barrel-related columns.
AB  - Tactile information acquired through the vibrissae is of high behavioral
      relevance for rodents. Numerous physiological studies have shown adaptive
      plasticity of cortical receptive field properties due to stimulation and/or
      manipulation of the whiskers. However, the cellular mechanisms leading to these
      plastic processes remain largely unknown. Although genomic responses are
      anticipated to take place in this sequel, virtually no data so far exist for
      freely behaving animals concerning this issue. Thus, adult rats were placed
      overnight in an enriched environment and most of them were also subjected to
      clipping of different sets of whiskers. This type of stimulation led to a
      specific and statistically significant increase in the expression of the protein
      products of the inducible transcription factors c-Fos, JunB, inducible cyclic-AMP
      early repressor and Krox-24 (also frequently named Zif268 or Egr-1), but not c
      Jun. The response was found in columns of the barrel cortex corresponding to the
      stimulated vibrissae; it displayed a layer-specific pattern. However, no
      induction of transcription factors was observed in the subcortical relay stations
      of the whisker-to-barrel pathway, i.e. the trigeminal nuclei and the ventrobasal
      complex. These results strongly suggest that a coordinated transcriptional
      response is initiated in the barrel cortex as a consequence of processing of
      novel environmental stimuli.

PMID- 10924948
TI  - Chronic treatment of old rats with donepezil or galantamine: effects on memory,
      hippocampal plasticity and nicotinic receptors.
AB  - The function of the cholinergic system is known to change during normal aging and
      in pathological conditions such as Alzheimer's disease. The present study was
      designed to assess, within the same group of old animals, the behavioral,
      electrophysiological and neurochemical effects of chronic treatment with agents
      that increase the function of the cholinergic system through both muscarinic and
      nicotinic mechanisms. Doses were determined that produced 60% cholinesterase
      inhibition by donepezil and galantamine for the old rats. This was chosen to be
      analogous to therapeutic levels achieved for treatment of human Alzheimer's
      disease patients with these agents. Because of the well-known age-related changes
      in spatial memory and hippocampal synaptic plasticity, spatial working memory in
      the radial eight-arm maze and hippocampal long-term potentiation induction and
      decay, as well as nicotinic receptor density and affinity, were measured in old
      rats implanted with minipumps that delivered donepezil, galantamine or saline.
      There was no effect of drug treatment on baseline synaptic transmission or on the
      threshold or magnitude of long-term potentiation induction. Both drug treatment
      groups, however, showed significantly extended long-term potentiation decay times
      at the perforant path-granule cell synapse over the saline control animals, as
      measured during the week following induction. Both drugs also elevated the number
      of nicotinic receptors within the hippocampus and neocortex. This is the first
      demonstration of cholinergic modulation of synaptic plasticity over the time
      course of days. Furthermore, the durability of long-term potentiation was
      significantly, positively correlated with nicotinic receptor binding in the
      hippocampus. Chronic treatment with donepezil or galantamine had no significant
      effect on a well-learned spatial working memory task on the radial maze. These
      data suggest that the therapeutic doses of cholinesterase inhibitors used to
      treat patients with Alzheimer's disease may have effects on neurophysiology and
      neurochemistry that are close to the threshold for producing detectable
      behavioral improvements.

PMID- 10924949
TI  - Effect of phospholipase C and protein kinase C following cholinergic denervation
      and hippocampal sympathetic ingrowth in rat hippocampus.
AB  - Following cholinergic denervation of the hippocampus by medial septal lesions, an
      unusual neuronal reorganization occurs in which peripheral adrenergic fibers
      arising from the superior cervical ganglia grow into the hippocampus (hippocampal
      sympathetic ingrowth). We have reported previously that cholinergic denervation
      and hippocampal sympathetic ingrowth differentially affected cholinergically
      stimulated phosphoinositide hydrolysis, concentration and affinity of muscarinic
      receptors, Go-protein level and protein kinase C activity. To complete these
      studies, we determined whether cholinergic denervation and hippocampal
      sympathetic ingrowth influenced phospholipase C and protein kinase C expression
      in dorsal hippocampal membranes and cytosol. Using immunoblotting methods, the
      results showed that the 100,000 mol. wt subunit of phospholipase Cbeta was
      increased in the membrane fraction in the hippocampal sympathetic ingrowth group
      by 45% compared to controls and the 150,000 mol.wt subunit was increased by 75%
      and 59% compared to controls and cholinergic denervation, respectively. For
      protein kinase C detection, immunoblots were prepared using antibodies selective
      for "classical" protein kinase C members (alpha, beta, gamma) and for the "novel"
      protein kinase C subfamily members (delta, &theta;). Membrane protein kinase
      Cbeta was decreased in hippocampal sympathetic ingrowth by 35% compared to
      controls and by 41% compared to cytosolic hippocampal sympathetic ingrowth.
      Membrane protein kinase Cbeta was decreased in cholinergic denervation by 28%
      compared to controls. When compared to membranes from controls and the
      cholinergic denervation group, and to cytosolic fractions from the hippocampal
      sympathetic ingrowth groups, respectively, the following membrane protein kinase
      isoforms were found to be decreased by hippocampal sympathetic ingrowth: gamma by
      55%, 40% and 57%; delta by 91.5%, 70% and 120%; theta; by 95%, 100% and 86%.In
      conclusion, our results may indicate the connection between the previously
      reported differential influence of hippocampal sympathetic ingrowth and
      cholinergic denervation on cholinergically stimulated phosphoinositol hydrolysis.
      The "normalization" of phosphoinositol hydrolysis found in hippocampal
      sympathetic ingrowth may be due to the increase in phospholipase Cbeta expression
      in hippocampal sympathetic ingrowth membrane fractions. Since the activation of
      protein kinase C is known to block phosphoinositol hydrolysis, hippocampal
      sympathetic ingrowth "normalization" of phosphoinositol hydrolysis may result
      from a reduction in protein kinase expression in hippocampal sympathetic ingrowth
      membranes.

PMID- 10924950
TI  - X-irradiation causes a prolonged reduction in cell proliferation in the dentate
      gyrus of adult rats.
AB  - The effects of X-irradiation on proliferating cells in the dentate subgranular
      zone were assessed in young adult Fisher 344 rats exposed to a range of X-ray
      doses and followed for up to 120 days. Apoptosis was quantified using morphology
      and end-labeling immunohistochemistry, and cell proliferation was detected using
      antibodies against the thymidine analog BrdU and the cyclin-dependent kinase
      p34(cdc2). Radiation-induced apoptosis occurred rapidly, with maximum
      morphological and end-labeling changes observed 3-6h after irradiation. Twenty
      four hours after irradiation cell proliferation was significantly reduced
      relative to sham-irradiated controls. The number of apoptotic nuclei increased
      rapidly with radiation dose, reaching a plateau at about 3Gy. The maximum number
      of apoptotic nuclei was substantially higher than the number of proliferating
      cells, suggesting that non-proliferating as well as proliferating cells in the
      subgranular zone were sensitive to irradiation. Subgranular zone cell
      proliferation was significantly reduced relative to age-matched controls 120 days
      after doses of 5Gy or higher. These findings suggest that neural precursor cells
      of the dentate gyrus are very sensitive to irradiation and are not capable of
      repopulating the subgranular zone at least up to 120 days after irradiation. This
      may help explain, in part, how ionizing irradiation induces cognitive impairments
      in animals and humans.

PMID- 10924951
TI  - Complex motor disturbances in a sequential double lesion rat model of
      striatonigral degeneration (multiple system atrophy).
AB  - This study characterizes paw reaching, stepping and balance abnormalities in a
      double lesion rat model of striatonigral degeneration, the core pathology
      underlying levodopa unresponsive parkinsonism associated with multiple system
      atrophy. Extensive unilateral nigral or striatal lesions induced by 6
      hydroxydopamine or quinolinic acid, respectively, produced a similarly marked
      contralateral paw reaching deficit without further deterioration following a
      secondary (complementary) lesion of ipsilateral striatum or substantia nigra.
      Contralateral stepping rates were reduced by unilateral 6-hydroxydopamine lesions
      without further deterioration following the secondary striatal lesion. In
      contrast, initial unilateral striatal quinolinic acid injections induced
      bilateral stepping deficits that significantly worsened contralaterally following
      the secondary nigral lesion. Contralateral sidefalling rates were significantly
      increased following primary nigral and striatal lesions. Secondary nigral but not
      secondary striatal lesions worsened contralateral sidefalling rates. Histological
      studies revealed subtotal (>90%) depletion of dopaminergic neurons in substantia
      nigra pars compacta and variable degrees of striatal degeneration depending on
      the lesion sequence. Animals pre-lesioned with 6-hydroxydopamine showed
      significantly larger residual striatal surface areas following the secondary
      striatal quinolinic acid lesion compared to animals with primary striatal
      quinolinic acid lesions (P<0.001). These findings are in line with previous
      experimental studies demonstrating that striatal dopamine depletion confers
      neuroprotection against subsequent excitotoxic injury. Whether loss of
      dopaminergic neurons protects against the striatal disease process occurring in
      multiple system atrophy (Parkinson-type) remains to be elucidated. In summary,
      this is the first experimental study to investigate spontaneous motor behaviour
      in a unilateral double lesion rat model. Our observations are consistent with a
      complex interaction of nigral and striatal lesions producing distinct behavioural
      and histological changes depending on the lesion sequence. Tests of forelimb
      akinesia and complex motor behaviour appear to provide a reliable tool that will
      be helpful for monitoring the effects of interventional strategies such as
      embryonic neuronal transplantation in the rat model of striatonigral
      degeneration.

PMID- 10924952
TI  - High and low responders to novelty: effects of adrenergic agents on the
      regulation of accumbal dopamine under challenged and non-challenged conditions.
AB  - The main goal of this study was to provide in vivo neurochemical evidence that
      mesolimbic alpha- and beta-adrenoceptors direct the release of mesolimbic
      dopamine. Both high responders to novelty and low responders to novelty were used
      to study the effects of intra-accumbal administered adrenergic agents on the
      dopamine release in the nucleus accumbens during two conditions, namely at rest
      (non-challenge) and when exposed to a "new cage" (challenge). Under non
      challenged condition: phenylephrine (alpha-adrenergic agonist) induced a dose
      dependent increase in dopamine release that was significantly larger in high
      responders; phentolamine (alpha-adrenoceptor antagonist) also induced a dose
      dependent increase in dopamine that was significantly larger in low responders;
      isoproterenol (beta-adrenoceptor agonist) induced a dose-dependent increase in
      dopamine that did not differ between the two types of rat; propranolol (beta
      adrenoceptor antagonist) did not change the dopamine release. Under challenged
      condition: phenylephrine and phentolamine both increased dopamine release without
      type-specific differences; only in low responders did isoproterenol increase the
      novelty-induced dopamine release; only in high responders did propranolol
      decrease the novelty-induced dopamine release. The in vivo neurochemical data are
      discussed in view of the outcome of earlier reported in vitro studies and
      pharmaco-behavioral studies. Overall the data reveal that mesolimbic
      noradrenaline has a dual role in the nucleus accumbens. It is argued that
      stimulation of alpha-adrenoceptors and beta-adrenoceptors, located
      postsynaptically on dopamine nerve-endings, inhibits and facilitates,
      respectively, dopamine release, whereas stimulation of presynaptic alpha
      adrenoceptors inhibits the release of noradrenaline and, subsequently,
      disinhibits the release of dopamine. Moreover, it is argued that non-challenged
      high responders have a relatively low (alpha/beta) noradrenergic tonus that
      changes into a relatively high (alpha/beta) noradrenergic tonus during challenge,
      and that non-challenged low responders have a relatively high (alpha) adrenergic
      tonus that changes into a relatively low (alpha) noradrenergic tonus during
      challenge. In general, the present data clearly reveal that both alpha- and beta
      adrenoceptors differentially regulate dopamine release in the nucleus accumbens.
      This regulation is individual-specific and depends on the test-condition
      (challenged versus non-challenged).

PMID- 10924953
TI  - Distinct cellular distribution of GABA(B)R1 and GABA(A)alpha1 receptor
      immunoreactivity in the rat substantia nigra.
AB  - GABA is one of the most important inhibitory neurotransmitters in the substantia
      nigra. Functions of GABA are mediated by two major types of GABA receptors,
      namely the GABA(A) and GABA(B) receptors. Subunits of both the GABA(A) and
      GABA(B) receptors have been cloned and functional characteristics of the
      receptors depend on their subunit compositions. In order to characterize the
      cellular localization of GABA(B)R1 and GABA(A)alpha1 subunit immunoreactivity in
      subpopulations of neurons in the rat substantia nigra, double and triple
      immunofluorescence was employed. Over 90% of tyrosine hydroxylase-immunoreactive
      neurons in the substantia nigra pars compacta were found to display
      immunoreactivity for GABA(B)R1. In contrast, immunoreactivity for GABA(A)alpha1
      was found to be primarily displayed by neurons in the substantia nigra pars
      reticulata. Around 85% of the GABA(A)alpha1-immunoreactive reticulata neurons
      were found to display parvalbumin immunoreactivity and some GABA(A)alpha1
      positive reticulata neurons were found to be parvalbumin negative. In addition,
      triple-labeling experiments revealed that at the single cell level, the tyrosine
      hydroxylase-positive, i.e. the dopaminergic neurons in the compacta displayed
      intense immunoreactivity for GABA(B)R1 but not GABA(A)alpha1 receptors. The
      parvalbumin-positive neurons in the reticulata displayed intense immunoreactivity
      for GABA(A)alpha1 but not GABA(B)R1 receptors. The present results demonstrate in
      the same sections that there is a distinct pattern of localization of GABA(B)R1
      and GABA(A)alpha1 receptor immunoreactivity in different subpopulations of the
      rat substantia nigra and provide anatomical evidence for GABA neurotransmission
      in the subpopulations of nigral neurons.

PMID- 10924955
TI  - Conditioning effects of repetitive mild neurotrauma on motor function in an
      animal model of focal brain injury.
AB  - A weight drop model of brain injury was used to determine the effects of
      repetitive mild brain injury on motor function, heat shock protein and glial
      fibrillary acidic protein expression in the anesthetized, adult male, Sprague
      Dawley rat. Repetitive mild brain injury was produced when animals received a
      series of three mild injuries spaced three days apart. A separate group of
      repetitive mild injured animals also received a subsequent severe brain injury
      between three and five days after the last mild injury. All animals were trained
      on a beam-walking test prior to surgery. The mild, repetitive mild and repetitive
      mild plus severe brain injury groups showed no motor deficits in the beam-walking
      test, whereas the animals with only severe brain injury showed significant motor
      deficits (increase in number of footslips) in the beam-walking test that
      recovered within eight days after injury. Both repetitive mild plus severe injury
      and severe injury only animals had cortical necrotic cavities of similar size in
      the region of the hindlimb motor cortex. Both the repetitive mild and severe
      brain-injured animals had marked heat shock protein 27kDa and glial fibrillary
      acidic protein staining in the cerebral cortex. Fluoro-Jade, heat shock protein
      27kDa and 72kDa labeling indicated that there were widespread effects on
      cortical, subcortical and spinal neurons and glial cells after repetitive mild
      brain injury. These results suggest that repetitive mild brain injury conditions
      the brain so that subsequent brain injury at the same site has no effect on motor
      function. Furthermore, repetitive mild injury-induced activation of processes
      distant to the primary injury site may have a role in activation of secondary
      sites involved in recovery of motor function.

PMID- 10924954
TI  - Brainstem regions with neuronal activity patterns correlated with priming of
      locomotor stepping in the anesthetized rat.
AB  - Locomotor stimulation in the perifornical hypothalamus produces a transient
      facilitation of subsequent locomotion, a priming effect, such that stepping to a
      second train of stimulation occurs with a shorter latency of onset and increased
      amplitude. Neurons responsible for the initiation of this facilitated stepping
      presumably respond to locomotor stimulation with a similar priming effect, i.e.
      either a shorter latency or a larger change in activity rate. This study used
      anesthetized rats (urethane, 800mg/kg) to compare brainstem regions in terms of
      the relative rates of occurrence of single neurons that showed both specific
      responses to locomotor stimulation and also priming effects. Specific responses
      were characterized by a progressive increase in activity prior to the first step
      (a Type I pattern). In that they co-varied in time with the increased probability
      of stepping onset, Type I responses were more specific than Type II responses,
      which peaked early in the stimulation train several seconds before the onset of
      stepping. Regions with high proportions of neurons showing Type I responses and
      priming effects included the anterior dorsal tegmentum lateral to the central
      gray, the oral pontine reticular nucleus and the medial gigantocellular nucleus.
      Few Type I neurons showed a modulation of activity related to the step cycle.
      Type I primed neurons were uncommon in the cuneiform and the pedunculopontine
      regions, but neurons showing other patterns (decreases and antidromic responses)
      were relatively prevalent there. The ventral tegmental area was generally
      unresponsive. The results indicate that stepping elicited by perifornical
      stimulation in the anesthetized rat is mediated by circuits that differ at
      midbrain levels from the circuits implicated in other types of locomotion. Two
      regions, the anterior dorsal tegmentum and the oral pontine reticular nucleus,
      warrant further attention to determine their possible roles in the initiation of
      locomotion.

PMID- 10924956
TI  - The aspirin metabolite sodium salicylate causes focal cerebral hemorrhage and
      cell death in rats with kainic acid-induced seizures.
AB  - Aspirin (acetylsalicylic acid), and its main metabolite sodium salicylate, have
      been shown to protect neurons from excitotoxic cell death in vitro. The objective
      of our study was to investigate the possible neuroprotective effects of sodium
      salicylate in vivo in rats with kainic acid-induced seizures, a model for
      temporal lobe epilepsy in human patients. Male Sprague-Dawley rats received
      intraperitoneal injections of kainic acid either alone, or with sodium salicylate
      given before and for 40h after kainic acid injections. The control group received
      either phosphate-buffered saline or sodium salicylate without co-administration
      of kainic acid. Animals developed status epilepticus, which was aborted 1.5-2h
      later with diazepam. On day 3 following kainic acid-induced seizures, animals
      received bromodeoxyuridine to measure cellular proliferation, and were killed
      under anesthesia 24h later. Brains were removed, sectioned, and analysed for
      gross histological changes, evidence of hemorrhage, DNA fragmentation, cellular
      proliferation, and microglial immunohistochemistry. We report that sodium
      salicylate did not protect neurons from seizure-induced cell death, and to the
      contrary, it caused focal hemorrhage and cell death in the hippocampal formation
      and the entorhinal/piriform cortex of rats with kainic acid-induced seizures.
      Hemorrhage was never observed in animals that received vehicle, kainic acid or
      sodium salicylate only, which indicated that sodium salicylate exerted its effect
      only in animals with seizures, and was confined to select regions of the brain
      that undergo seizure activity. Large numbers of cells displaying DNA
      fragmentation were detected in the hippocampal formation, entorhinal/piriform
      cortex and the dorsomedial thalamic nucleus of rats that received kainic acid or
      kainic acid in combination with sodium salicylate. Bromodeoxyuridine
      immunohistochemistry revealed large numbers of proliferating cells in and around
      the areas with most severe neural injury induced by kainic acid or kainic acid co
      administered with sodium salicylate. These same brain regions displayed intense
      staining with a microglia-specific marker, an indication of microglial activation
      in response to brain damage. In all cases, the degree of cell death, cell
      proliferation and microglia staining was more severe in animals that received the
      combination of kainic acid and sodium salicylate when compared to animals that
      received kainic acid alone. We hypothesize that our findings are attributable to
      sodium salicylate-induced blockade of cellular mechanisms that protect cells from
      calcium-mediated injury. These initial observations may have important clinical
      implications for patients with epilepsy who take aspirin while affected by these
      conditions, and should promote further investigation of this relationship.

PMID- 10924957
TI  - Axotomy-induced change in the properties of (S)-alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionate receptor channels in rat motoneurons.
AB  - Properties of (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)
      receptor channels were studied in fluorescence-labelled control and axotomized
      motoneurons in spinal cord slices using a patch-clamp technique. Axotomy
      performed on the third postnatal day resulted in motoneuron death. Application of
      AMPA or kainate induced large whole-cell currents, but outside-out patches
      isolated from control motoneurons were either unresponsive or displayed only
      single-channel activity in response to rapid application of AMPA. Measurement of
      AMPA receptor channel openings in outside-out patches revealed multiple single
      channel conductance levels: 12.2+/-1.0, 21. 9+/-1.5 and 32.6+/-3.2pS. In control
      motoneurons dialysed with spermine, the current-voltage relationship of responses
      induced by activation of AMPA receptor channels exhibited various degrees of
      inward rectification. The rectification index, the ratio of responses at +40 and 
      60mV, was used to compare the degree of inward rectification. The mean values of
      rectification index of responses to focal application of AMPA and AMPA receptor
      mediated excitatory postsynaptic currents induced by focal electric stimulation
      were 0. 64+/-0.17 and 0.50+/-0.27, respectively. In axotomized motoneurons, the
      degree of rectification was significantly less for both responses induced by
      application of AMPA and for excitatory postsynaptic currents (0.91+/-0.09 and
      0.95+/-0.12, respectively). Deactivation of AMPA receptors assessed from
      motoneuron excitatory postsynaptic currents at -70 mV was independent of
      postnatal age, with tau(fast)=0.88+/-0.35ms (A(fast)=78.2+/-11.8%) and
      tau(slow)=6. 3+/-3.2ms. In axotomized motoneurons, the decay time constants of
      excitatory postsynaptic currents were similar, tau(fast)=0.91+/-0. 42ms
      (A(fast)=85.8+/-12.6%) and tau(slow)=5.9+/-3.4ms. However, the mean amplitude of
      excitatory postsynaptic currents was only 43% of the amplitude recorded in
      control motoneurons. The results show that the current induced by activation of
      AMPA receptors in neonatal motoneurons is mediated by opening of both Ca(2+)
      permeable and Ca(2+)-impermeable channels. As a result of axotomy, an
      experimental model of neurodegeneration, AMPA receptor channels in injured
      motoneurons destined to die become predominantly Ca(2+) impermeable. These
      findings suggest phenotypic control of AMPA receptor channel properties,
      presumably by affecting their subunit composition.

PMID- 10924958
TI  - Phenotypical segregation among female rat hypothalamic gonadotropin-releasing
      hormone neurons as revealed by the sexually dimorphic coexpression of
      cholecystokinin and neurotensin.
AB  - The neuroendocrine control of the gonad is exerted primarily by the gonadotropin
      releasing hormone neurons located in the septum and the hypothalamus. Despite
      their sexually dimorphic activity, tonic in males and phasic in females, these
      neurons have not appeared qualitatively different between sexes in intrinsic
      organization or chemical phenotype. Here, by using multiple-label
      immunocytochemistry, it is demonstrated that the phenotype of gonadotropin
      releasing hormone neurons is sex specific. In females only, 54.5% of them co
      expressed cholecystokinin immunoreactivity and 29.4% additionally expressed
      neurotensin immunoreactivity. These multipeptidergic neurons were observed in the
      hypothalamus but not in the septum. During postnatal development, cholecystokinin
      and neurotensin immunoreactivities were first detected in gonadotropin-releasing
      hormone-containing axons of the median eminence at vaginal opening, suggesting an
      involvement of the neuropeptides in peri-ovulatory events. This peptidergic
      phenotype was not apparent in females ovariectomized as adults but was reinstated
      by estradiol treatment. In adult males, the testicle does not control this
      phenotype because orchidectomized adults did not display it, whatever the post
      operative delay (one to five weeks) or substitutive chronic steroid treatment
      (testosterone or estradiol). The testicle may, however, masculinize the phenotype
      neonatally because estradiol or testosterone treatment in adulthood induced an
      expression of cholecystokinin immunoreactivity in gonadotropin-releasing hormone
      containing axons of the median eminence in both males and females that were
      gonadectomized at birth. This procedure, however, failed to significantly induce
      an expression of neurotensin immunoreactivity, suggesting a role of the postnatal
      ovary on this element of the chemistry of gonadotropin-releasing hormone
      neurons.Thus, the gonad permanently organizes the gonadotropin-releasing hormone
      neuronal population, resulting, at least in females, in a mosaic of
      phenotypically distinct, functional subunits.

PMID- 10924959
TI  - The organum vasculosum of the lamina terminalis regulates noradrenaline release
      in the anterior hypothalamic nucleus.
AB  - Changes in either plasma sodium concentration or arterial pressure can
      differentially affect hypothalamic neurons. For instance, increases in plasma
      NaCl concentration decrease noradrenaline release from nerve terminals in the
      anterior hypothalamic nucleus, while increases in arterial pressure unrelated to
      an elevation in plasma NaCl enhance noradrenaline release in anterior
      hypothalamic nucleus. The present study tests the hypothesis that in the rat the
      organum vasculosum of the lamina terminalis (an osmosensitive area of the brain)
      detects rises in plasma NaCl concentration and conveys this information to
      anterior hypothalamic nucleus. The axons projecting from the organum vasculosum
      of the lamina terminalis to the hypothalamus were unilaterally cut immediately
      caudal to organum vasculosum of the lamina terminalis, and five days later, 3
      methoxy-4-hydroxy phenylglycol (the major metabolite of noradrenaline in brain)
      was continuously monitored in the ipsilateral or contralateral anterior
      hypothalamic nucleus in response to an intravenous infusion of hypertonic saline.
      In spontaneously hypertensive rats, the infusion decreased the 3-methoxy-4
      hydroxy phenylglycol concentration by 24+/-2% in the anterior hypothalamic
      nucleus contralateral to the lesion, and in control spontaneously hypertensive
      rats. In contrast, in the anterior hypothalamic nucleus ipsilateral to the
      lesion, hypertonic saline infusion caused a 58+/-3% increase in 3-methoxy-4
      hydroxy phenylglycol. These data support the hypothesis that the organum
      vasculosum of the lamina terminalis is part of the circuit that transmits
      information concerning plasma NaCl concentration to anterior hypothalamic
      nucleus.

PMID- 10924960
TI  - Regulation of the expression and phosphorylation of microtubule-associated
      protein 1B during regeneration of adult dorsal root ganglion neurons.
AB  - Microtubule-associated protein 1B is a major constituent of the neuronal
      cytoskeleton during the early stages of development. This protein and its
      phosphorylated isoform, microtubule-associated protein 1B-P, defined by the
      monoclonal antibody 1B-P [Boyne L. J. et al. (1995) J. Neurosci. Res. 40, 439
      450], are present in growing axons and concentrated in the distal end near the
      growth cone. In most regions of the central nervous system, microtubule
      associated protein 1B and microtubule-associated protein 1B-P are developmentally
      down-regulated. They remain, however, at relatively high levels in the adult
      peripheral nervous system, where microtubule-associated protein 1B-P is localized
      exclusively in axons. The aim of this study was to examine the levels of
      microtubule-associated protein 1B and its phosphorylated isoform during
      regenerative growth of peripheral axons. Following transection and re-apposition
      of the sciatic nerve at midthigh, the levels of total microtubule-associated
      protein 1B, microtubule-associated protein 1B-P and microtubule-associated
      protein 1B messenger RNA were analysed in dorsal root ganglion neurons and
      sciatic nerve axons using western blots and RNase protection assays. After the
      lesion, there was a small decrease in the levels of microtubule-associated
      protein 1B and its messenger RNA in dorsal root ganglion neurons. The proximal
      axonal stump showed a similar decrease in the levels of microtubule-associated
      protein 1B 30days after lesion and returned to normal 60-90days post-lesion. In
      the distal stump of the sciatic nerve, the levels of microtubule-associated
      protein 1B increased dramatically and rapidly between three and 14days, but the
      protein was localized mainly in activated Schwann cells and myelin-like
      structures, and not in axons [Ma D. et al. (1999) Brain Res. 823, 141-153]. With
      the regeneration of axons into the distal stump, an intense expression of
      microtubule-associated protein 1B was observed in these axons. Microtubule
      associated protein 1B-P, however, disappeared from the degenerated distal axonal
      stump as early as three days post-operation, and was absent in the regenerating
      axons and in Schwann cells between three and 14days. The levels of microtubule
      associated protein 1B-P recovered slowly and did not reach the normal levels even
      after 90days post-operation. In contrast to the response following transection,
      the levels of microtubule-associated protein 1B and microtubule-associated
      protein 1B-P were much less affected after nerve crush. We propose that the
      relatively high levels of microtubule-associated protein 1B and its messenger RNA
      in adult dorsal root ganglions support peripheral neuron regeneration. The
      presence of microtubule-associated protein 1B in the regenerating axons suggests
      that microtubule-associated protein 1B is involved in axonal growth during
      peripheral nerve regeneration. However, the phosphorylated microtubule-associated
      protein 1B-P isoform, associated with growing axons during development, is not
      present in the regenerating axons after transection, presumably because of
      changes in the activities of kinases and phosphatases associated with the injury.
      These observations underscore the difference between axonal development and
      regeneration and the importance of injury-related effects that occur locally.

PMID- 10924961
TI  - Differential effects of calcitonin gene-related peptide and calcitonin gene
      related peptide 8-37 upon responses to N-methyl-D-aspartate or (R, S)-alpha-amino
      3-hydroxy-5-methylisoxazole-4-propionate in spinal nociceptive neurons with knee
      joint input in the rat.
AB  - Calcitonin gene-related peptide is involved in the spinal processing of
      nociceptive input from the knee joint and in the generation and maintenance of
      joint inflammation-evoked hyperexcitability of spinal cord neurons. The present
      study examined whether this peptide influences the excitation of nociceptive
      spinal cord neurons by agonists at the N-methyl-D-aspartate and the non-N-methyl
      D-aspartate [(R, S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate
      (AMPA)/kainate] receptors, both of which are essential for the excitation and
      hyperexcitability of spinal cord neurons. In anaesthetized rats extracellular
      recordings were made from dorsal horn neurons with knee input, and compounds were
      administered ionophoretically close to the neurons recorded. When calcitonin gene
      related peptide was administered the responses of the neurons to the application
      of both N-methyl-D-aspartate and AMPA were increased. The coadministration of the
      antagonist calcitonin gene-related peptide 8-37 had no effect on the responses to
      N-methyl-D-aspartate, but it prevented the enhancement of the responses to N
      methyl-D-aspartate by calcitonin gene-related peptide. By contrast, the
      administration of calcitonin gene-related peptide 8-37 enhanced the responses of
      the neurons to AMPA, and it did not antagonize but rather increased the effects
      of calcitonin gene-related peptide on these responses. The data suggest that the
      facilitatory role of calcitonin gene-related peptide on the development and
      maintenance of inflammation-evoked hyperexcitability is caused at least in part
      by the modulation of the activation of the dorsal horn neurons through their N
      methyl-D-aspartate and non-N-methyl-D-aspartate receptors. The different effects
      of calcitonin gene-related peptide 8-37 on the respones to N-methyl-D-aspartate
      and AMPA suggest that different intracellular pathways may facilitate the
      activation of N-methyl-D-aspartate and ionotropic non-N-methyl-D-aspartate
      receptors.

PMID- 10924962
TI  - Role of L- and N-type calcium channels in the pathophysiology of traumatic spinal
      cord white matter injury.
AB  - Recent work has suggested a potential role for voltage-gated Ca(2+) channels in
      the pathophysiology of anoxic central nervous system white matter injury. To
      examine the relevance of these findings to neurotrauma, we conducted
      electrophysiological studies with inorganic Ca(2+) channels blockers and L- and N
      subtype-specific calcium channel antagonists in an in vitro model of spinal cord
      injury. Confocal immunohistochemistry was used to examine for localization of L-
      and N-type calcium channels in spinal cord white matter tracts. A 30-mm length of
      dorsal column was isolated from the spinal cord of adult rats, pinned in an in
      vitro recording chamber and injured with a modified clip (2g closing force) for
      15s. The functional integrity of the dorsal column was monitored
      electrophysiologically by quantitatively measuring the compound action potential
      at two points with glass microelectrodes. The compound action potential decreased
      to 71.4+/-2.0% of control (P<0. 05) after spinal cord injury. Removal of
      extracellular Ca(2+) promoted significantly greater recovery of compound action
      potential amplitude (86.3+/-7.6% of control; P< 0.05) after injury. Partial
      blockade of voltage-gated Ca(2+) channels with cobalt (20 microM) or cadmium (200
      microM) conferred improvement in compound action potential amplitude. Application
      of the L-type Ca(2+) channel blockers diltiazem (50 microM) or verapamil (90
      microM), and the N-type antagonist omega-conotoxin GVIA (1 microM), significantly
      enhanced the recovery of compound action potential amplitude postinjury. Co
      application of the L-type antagonist diltiazem with the N-type blocker omega
      conotoxin GVIA showed significantly greater (P<0.05) improvement in compound
      action potential amplitude than application of either drug alone. Confocal
      immunohistochemistry with double labelling for glial fibrillary acidic protein,
      GalC and NF200 demonstrated L- and N-type Ca(2+) channels on astrocytes and
      oligodendrocytes, but not axons, in spinal cord white matter. In conclusion, the
      injurious effects of Ca(2+) in traumatic central nervous system white matter
      injury appear to be partially mediated by voltage-gated Ca(2+) channels. The
      presence of L- and N-type Ca(2+) channels on periaxonal astrocytes and
      oligodendrocytes suggests a role for these cells in post-traumatic axonal
      conduction failure.

PMID- 10924963
TI  - Opioid peptide messenger RNA expression is increased at spinal and supraspinal
      levels following excitotoxic spinal cord injury.
AB  - Spinal cord injury in rats is known to cause anatomical, physiological and
      molecular changes within the spinal cord. These changes may account for
      behavioral syndromes that appear following spinal cord injury, syndromes believed
      to be related to the clinical condition of chronic pain. Intraspinal injection of
      quisqualic acid produces an excitotoxic injury with pathological characteristics
      similar to those associated with ischemic and traumatic spinal cord injury. In
      addition, recent studies have demonstrated changes in blood flow, neuronal
      excitability and gene expression in the brain following excitotoxic injury,
      indicating that behavioral changes may result from modification of neuronal
      substrates at supraspinal levels of the neuraxis. Because changes in spinal
      opioid peptide expression have been demonstrated in models of traumatic spinal
      cord injury and chronic pain, the present study investigated messenger RNA
      expression of the opioid peptides, preproenkephalin and preprodynorphin, at
      spinal and supraspinal levels following excitotoxic spinal cord injury. Male,
      Long-Evans rats were given three intraspinal injections of quisqualic acid (total
      1.2 microl, 125mM). After one, three, five, seven or 10days, animals were killed
      and quantitative in situ hybridization performed on regions of the spinal cord
      surrounding the lesion site, as well as whole-brain sections through various
      levels of the thalamus. Preproenkephalin and preprodynorphin expression was
      increased in spinal cord areas adjacent to the site of quisqualic injection and
      in cortical regions associated with nociceptive function, preproenkephalin in the
      cingulate cortex and preprodynorphin in the parietal cortex, both ipsilaterally
      and contralaterally at various time-points following injury. These results
      further our knowledge of the secondary events that occur following spinal cord
      injury, specifically implicating supraspinal opioid systems in the CNS response
      to spinal cord injury.

PMID- 10924964
TI  - Transmutability of dose and time. Commentary on the first report of RTOG 90003
      (K. K. FU et al.)

PMID- 10924965
TI  - Confirmation of improved local-regional control with altered fractionation in
      head and neck cancer.

PMID- 10924966
TI  - A Radiation Therapy Oncology Group (RTOG) phase III randomized study to compare
      hyperfractionation and two variants of accelerated fractionation to standard
      fractionation radiotherapy for head and neck squamous cell carcinomas: first
      report of RTOG 9003.
AB  - PURPOSE: The optimal fractionation schedule for radiotherapy of head and neck
      cancer has been controversial. The objective of this randomized trial was to test
      the efficacy of hyperfractionation and two types of accelerated fractionation
      individually against standard fractionation. METHODS AND MATERIALS: Patients with
      locally advanced head and neck cancer were randomly assigned to receive
      radiotherapy delivered with: 1) standard fractionation at 2 Gy/fraction/day, 5
      days/week, to 70 Gy/35 fractions/7 weeks; 2) hyperfractionation at 1. 2
      Gy/fraction, twice daily, 5 days/week to 81.6 Gy/68 fractions/7 weeks; 3)
      accelerated fractionation with split at 1.6 Gy/fraction, twice daily, 5
      days/week, to 67.2 Gy/42 fractions/6 weeks including a 2-week rest after 38.4 Gy;
      or 4) accelerated fractionation with concomitant boost at 1.8 Gy/fraction/day, 5
      days/week and 1.5 Gy/fraction/day to a boost field as a second daily treatment
      for the last 12 treatment days to 72 Gy/42 fractions/6 weeks. Of the 1113
      patients entered, 1073 patients were analyzable for outcome. The median follow-up
      was 23 months for all analyzable patients and 41.2 months for patients alive.
      RESULTS: Patients treated with hyperfractionation and accelerated fractionation
      with concomitant boost had significantly better local-regional control (p = 0.045
      and p = 0.050 respectively) than those treated with standard fractionation. There
      was also a trend toward improved disease-free survival (p = 0.067 and p = 0.054
      respectively) although the difference in overall survival was not significant.
      Patients treated with accelerated fractionation with split had similar outcome to
      those treated with standard fractionation. All three altered fractionation groups
      had significantly greater acute side effects compared to standard fractionation.
      However, there was no significant increase of late effects. CONCLUSIONS:
      Hyperfractionation and accelerated fractionation with concomitant boost are more
      efficacious than standard fractionation for locally advanced head and neck
      cancer. Acute but not late effects are also increased.

PMID- 10924967
TI  - Intratumoral microvessel density predicts local treatment failure of radically
      irradiated squamous cell cancer of the oropharynx.
AB  - PURPOSE: To determine the predictive value of intratumoral microvessel density
      (IMD), and of the expression of p53, vascular endothelial growth factor (VEGF)
      and thrombospondin-1 (TSP-1) for the radiocurability of patients with squamous
      cell cancer of the oropharynx. MATERIALS AND METHODS: 139 patients with squamous
      cell cancer of the oropharynx were radically irradiated (median dose, 74 Gy)
      between 1991 and 1997. Biopsies from 100 patients were processed for
      immunohistochemistry. IMD was determined in hot spot areas of tissue stained with
      anti-CD31 at a magnification of x200. Staining for p53 was considered positive if
      more than 10% of the cell nuclei overexpressed the protein. Immunostaining of
      VEGF and TSP-1 was assessed semiquantitatively. RESULTS: Increasing IMD (range,
      54-282) was strongly correlated with incomplete remission of both the primary
      tumors (p = 0.01) and lymph node metastases (p = 0.02). Moreover, multivariate
      Cox regression analysis revealed local failure-free survival to decline with
      increasing IMD (IMD continuous: risk ratio = 1.01 per increase of 1 microvessel,
      p = 0. 0001; IMD categorical: </= 80: baseline, 81-110: risk ratio = 2.71, 111
      130: risk ratio = 4.55, > 130: risk ratio = 13.01). Neither the expression of
      p53, nor that of VEGF or TSP-1 was associated with the treatment outcome or IMD,
      but VEGF and TSP-1 expression were positively correlated (p = 0.02). CONCLUSION:
      IMD represents a powerful and independent predictive factor for local treatment
      failure in radically irradiated patients with squamous cell cancer of the
      oropharynx.

PMID- 10924968
TI  - Does the combination of radiotherapy and debulking surgery favor survival in
      paranasal sinus carcinoma?
AB  - PURPOSE: To determine the contribution of debulking surgery on local control and
      survival in paranasal sinus tumors. As most patients present with locally
      advanced disease, the possibility of radical surgery is limited. Consequently,
      radiotherapy is often needed as monotherapy or as an adjunct to surgery. METHODS
      AND MATERIALS: Between 1977 and 1996, 73 patients (50 male: 23 female) with a
      paranasal sinus carcinoma were treated. The histology distribution was as
      follows: squamous cell carcinoma, 55%; adenocarcinoma, 19%; adenoid cystic
      carcinoma, 11%; and undifferentiated carcinoma, 15%. The clinical T
      classification was (UICC/TNM 1997): T2 14%, T3 27%, and T4 59%. Pathological neck
      nodes were found in 11% of patients. Treatment consisted of surgery only in 3,
      chemotherapy only in 1, radiotherapy only in 18, both surgery and radiotherapy in
      50 patients. One patient did not receive any treatment at all. Three patients had
      concurrent chemotherapy. Median follow-up was 66 months (range, 1-213 months).
      RESULTS: Five-year local control (LC) was 65% with combination of radiotherapy
      and debulking surgery in comparison with 47% with radiotherapy alone, but this
      difference was not statistically significant (p = 0.58). However, combination
      treatment gave significantly better 5-year overall survival (OS) (60% vs. 9%; p =
      0.001) and 5-year disease-free survival (DFS) (53% vs. 6%; p < 0. 0001). Cox
      regression analysis showed that pathologic N status (p = 0.04), palliative
      intention of treatment (p = 0.018), clinical orbital invasion (p = 0.003), and
      orbital wall invasion (p = 0.003) were parameters significantly associated with
      poor local control. Total radiation dose of greater than 65 Gy (p = 0.05) and
      treatment consisting of radiotherapy alone (p = 0.002) were associated with worse
      overall survival; for disease-free survival clinical orbital invasion (p =
      0.0005), age of greater than 65 years (p = 0.013) and pathologic T4
      classification (p = 0.002) were significant factors for an unfavorable outcome.
      In 19 of 73 patients, 26 serious (mainly ophthalmological) complications were
      reported; in the majority of these, the visual tract was (partly) included in the
      treatment fields because of tumor extension. To analyze on which basis patients
      were selected for the combination therapy, a logistic regression was performed,
      concluding that clinical T4 classification (p = 0.05), radiological evidence of
      skull base invasion (p = 0.005), age of greater than 65 years (p = 0.026),
      radiological evidence of nasopharynx invasion (p = 0.02), clinical suspicion of
      palate invasion (p = 0.02), and radiological evidence of skin invasion (p =
      0.009) were associated with choosing radiotherapy alone. CONCLUSION: Debulking
      surgery of paranasal sinus malignancies followed by high-dose radiotherapy to the
      involved sites was associated with better survival and (although not
      statistically significant) local control. Patient selection, based on clinical
      and radiological impression of tumor extension, was the main factor explaining
      these favorable results. We favor this combination regimen because the surgery
      gives quick relief of complaints and, at the same time, offers an excellent
      histologically proven staging method, enabling radiotherapy to be adjusted to the
      involved sites, thereby decreasing the risk of complications. This can all be
      achieved with a very low orbital exenteration rate.

PMID- 10924969
TI  - Postoperative brachytherapy alone for T1-2 N0 squamous cell carcinomas of the
      oral tongue and floor of mouth with close or positive margins.
AB  - PURPOSE: To evaluate the efficacy of postoperative brachytherapy alone (brachy)
      for Stage T1-2 squamous cell carcinomas (SCC) of the floor of mouth (FM) and the
      oral tongue (OT) with close or positive margins. METHODS AND MATERIALS: Between
      1979 and 1993, 36 patients with T1-2 N0 (24 T1, 12 T2) OT (19), and FOM (17) SCC
      with close or positive margins following surgery underwent postoperative brachy.
      Mean patient age was 56 years (range 37-81) and sex ratio was 3.5:1 male:female.
      Mean surgery to brachy interval was 36 days (range 16-68). The technique used was
      interstitial Iridium-192 ((192)Ir) brachytherapy with plastic tubes and manual
      afterloading. Mean total dose was 60 Gy (range 50-67.4) at a mean dose rate of
      0.64 Gy/h (range 0.32-0.94). Mean patient follow-up was 80 months. RESULTS: The 5
      year actuarial overall and cause-specific survivals of the entire group were 75%
      and 85%, respectively. The local control was 88.5% at 2 years, with a plateau
      apparent after 23 months. Of the 4 local relapses, 2 were salvaged with surgery
      and external beam radiotherapy (EBR). No tumor or treatment factors, including
      tumor size, margin status, disease site, or radiation dose, were correlated with
      local control. The 2 head and neck second primaries underwent curative treatment
      on nonirradiated tissue. One patient developed a grade 3 sequelae (bone and soft
      tissue necrosis). Grade 2-3 chronic sequelae were seen in 7 of 17 and 3 of 19 FOM
      and OT tumors, respectively (p = 0.09). CONCLUSION: Postoperative brachy is a
      promising approach in T1-2 N0 OT and FOM SCC with close or positive margins. This
      approach is associated with high rate of locoregional control and low risk of
      chronic sequelae, obviates major surgery, avoids potential sequelae of EBR
      (xerostomia, dysgueusia, fibrosis), and avoids treatment of second head and neck
      primary on nonirradiated tissues.

PMID- 10924970
TI  - Radiotherapy treatment planning and long-term follow-up with [(11)C]methionine
      PET in patients with low-grade astrocytoma.
AB  - PURPOSE: To evaluate the feasibility of [(11)C]-methionine positron emission
      tomography (MET PET) in radiotherapy (RT) treatment planning and long-term follow
      up in patients with low-grade glioma. PATIENTS: Thirteen patients with low-grade
      astrocytoma and 1 with anaplastic astrocytoma underwent sequential MET PET and
      magnetic resonance imaging (MRI) before and 3, 6, 12, and 21-39 months after RT,
      respectively. Ten patients were studied after initial debulking surgery or biopsy
      and 4 in the recurrence phase. METHODS: A total of 58 PET scans were performed.
      After transmission scanning, a median dose of 425 MBq of MET was injected
      intravenously and emission data was acquired 20 min after injection for 20 min.
      The uptake of MET in tumor area was measured as standardized uptake value (SUV)
      and tumor-to-contralateral brain SUV ratios were generated to assess irradiation
      effects on tumor metabolism. Functional imaging with PET was compared with
      concurrent MRI in designing the RT planning volumes and in assessment of response
      to RT during a median follow-up time of 33 months. RESULTS: In 12 patients (86%),
      tumor area was clearly discernible in the baseline PET study. In the remaining 2
      patients with a suspected residual tumor in MRI, PET showed only a diffuse uptake
      of MET interpreted as negative in the original tumor area. In the dose planning
      of RT, MET PET was helpful in outlining the gross tumor volume in 3 of 11 cases
      (27%), whereas PET findings either coincided with MRI (46%) or were less
      distinctive (27%) in other cases. In quantitative evaluation, patients with a low
      tumor SUV initially had significantly better prognosis than those with a high
      SUV. Tumor-to-contralateral brain uptake ratios of MET discriminated well
      patients remaining clinically stable from those who have since relapsed or died
      of disease. CONCLUSION: Quantitative MET PET has prognostic value at the time of
      initial treatment planning of low-grade glioma. Some patients may benefit of RT
      volume definition with MET PET, which seems to disclose residual tumor better
      than MRI in selected cases. Stable or decreasing uptake of MET in tumor area
      after RT during follow-up seems to be a favorable sign.

PMID- 10924971
TI  - Radiation-induced regional cerebral blood volume (rCBV) changes in normal brain
      and low-grade astrocytomas: quantification and time and dose-dependent
      occurrence.
AB  - PURPOSE: New tumor-conformal radiation-treatment modalities have been established
      with the intention to spare normal tissue while maintaining or improving local
      tumor control. To document radiation-induced changes in normal brain and low
      grade astrocytoma we measured regional cerebral blood volumes (rCBV) using a
      dynamic susceptibility-weighted contrast-enhanced MR technique (DSC-MRI). We
      attempted to assess pretherapeutic rCBV values and time- and dose-dependent
      changes following radiotherapy. METHODS AND MATERIALS: For prospective and
      longitudinal assessment of rCBV in normal brain and low-grade astrocytoma, 25
      patients with histologically proven fibrillary astrocytoma (WHO Grade II) were
      examined before radiotherapy and during follow-up. Based on CT- and MR-data sets
      in a stereotactic setup, three-dimensional (3D) treatment planning was done.
      Radiotherapy was delivered using fractionated stereotactic radiotherapy (FSRT) to
      mean and median total doses of 60.9 and 60 Gy, respectively (range, 55.8-66 Gy).
      During MR imaging for treatment planning and follow-up examinations, 55 T2
      weighted gradient echo images were acquired before, during, and after intravenous
      contrast bolus injection. The acquired signal-time curves were converted into
      concentration-time curves. The area under the tissue concentration-time curve was
      calculated and normalized to an integrated arterial input function. Thus,
      absolute rCBV values could be calculated. RESULTS: Pretherapeutic mean rCBV for
      normal gray (GM) and white brain matter (WM) were 7.2 +/- 2.7 and 3.6 +/- 1.5
      mL/100 g tissue, respectively. Mean rCBV for astrocytoma was 6.5 +/- 3.7 mL/100 g
      tissue. After radiotherapy, rCBV for GM and WM was significantly reduced (p <
      0.01) in high-dose areas (40-100% of total dose). A nonsignificant reduction was
      measured in low-dose areas (up to 40% of total dose). Reduction of rCBV in
      astrocytomas to a plateau level of 4.6 +/- 0.4 mL/100 g tissue was measured at 6
      months after radiotherapy and remained stable in locally controlled tumors.
      CONCLUSION: Monitoring of rCBV changes in normal brain and low-grade astrocytoma
      was feasible using a DSC-MRI technique. The method was able to document radiation
      effects in low-grade astrocytoma, even if the majority of tumors showed no change
      in diagnostic MR-imaging. Radiation induced decrease of rCBV in GM and WM was
      correlated to total dose delivered to a tissue area, with high doses causing a
      significant decrease. Minor decline of rCBV in GM and WM outside high-dose areas
      after stereotactic radiotherapy confirms the efficacy to spare normal brain
      tissue by the use of modern conformal radiotherapy techniques. Nonetheless, a
      critical minimal dose initiating rCBV changes is yet unknown.

PMID- 10924972
TI  - Importance of the mini-mental status examination in the treatment of patients
      with brain metastases: a report from the Radiation Therapy Oncology Group
      protocol 91-04.
AB  - PURPOSE: Little information is available on the importance of pretreatment Mini
      Mental Status Exam (MMSE) on long-term survival and neurologic function following
      treatment for unresectable brain metastases. This study examines the importance
      of the MMSE in predicting outcome in a group of patients treated with an
      accelerated fractionation regimen of 30 Gy in 10 daily fractions in 2 weeks.
      MATERIALS AND METHODS: The Radiation Therapy Oncology Group (RTOG) accrued 445
      patients to a Phase III comparison of accelerated hyperfractionated (AH)
      radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated
      fractionation (AF) of 30 Gy in 10 daily fractions from 1991 through 1995. All
      patients had histologic proof of malignancy at the primary site. Brain metastases
      were measurable by CT or MRI scan and all patients had a Karnofsky performance
      score (KPS) of at least 70 and a neurologic function classification of 1 or 2.
      Two hundred twenty-four patients were entered on the accelerated fractionated
      arm, and 182 were eligible for analysis (7 patients were judged ineligible, no
      MMSE information in 29, no survival data in 1, no forms submitted in 1). RESULTS:
      Average age was 60 years; 58% were male and 25% had a single intracranial lesion
      on their pretherapy evaluation. KPS was 70 in 32%, 80 in 31%, 90 in 29%, and 100
      in 14%. The average MMSE was 26.5, which is the lower quartile for normal in the
      U.S. population. The range of the MMSE scores was 11-30 with 30 being the
      maximum. A score of less than 23 indicates possible dementia, which occurred in
      16% of the patients prior to treatment. The median time from diagnosis to
      treatment was 5 days (range, 0-158 days). The median survival was 4.2 months with
      a 95% confidence interval of 3.7-5.1 months. Thirty-seven percent of the patients
      were alive at 6 months, and 17% were alive at 1 year. The following variables
      were examined in a Cox proportional-hazards model to determine their prognostic
      value for overall survival: age, gender, KPS, baseline MMSE, time until MMSE
      below 23, time since diagnosis, number of brain metastases, and radiosurgery
      eligibility. In all Cox model analyses, age, KPS, baseline MMSE, time until MMSE
      below 23, and time since diagnosis were treated as continuous variables.
      Statistically significant factors for survival were pretreatment MMSE (p =
      0.0002), and KPS (p = 0.02). Age was of borderline significance (p = 0.065) as
      well as gender (p = 0.074). A poorer outcome is associated with an increasing
      age, male gender, lower MMSE, and shorter time until MMSE below 23. Improvement
      in MMSE over time was assessed; 62 patients died prior to obtaining follow-up
      MMSE, and 30 patients had a baseline MMSE of 30 (the maximum), and, therefore, no
      improvement could be expected. Of the remaining 88, 48 (54.5%) demonstrated an
      improvement in their MMSE at any follow-up visit. Lack of decline of MMSE below
      23 was seen in long-term survivors, with 81% at 6 months and 66% at 1 year of
      patients maintaining a MMSE above 23. Analysis of time until death from brain
      metastases demonstrated that decreasing baseline MMSE (p = 0.003) and primary
      site (breast vs. lung vs. other p = 0.032) were highly associated with a terminal
      event. CONCLUSION: While gender and perhaps age remain significant predictors for
      survival, MMSE is also an important way of assessing a patient's outcome.
      Accelerated fractionation used in the treatment of brain metastases (30 Gy in 10
      fractions) appears to also be associated with an improvement in MMSE and a lack
      of decline of MMSE below 23 in long-term survivors.

PMID- 10924973
TI  - Secondary intracranial meningiomas after high-dose cranial irradiation: report of
      five cases and review of the literature.
AB  - PURPOSE: To review cases of secondary intracranial meningiomas following high
      dose cranial irradiation (>/= 10 Gy) identified in Slovenia between 1968 and
      1998, to determine their histological profile and to review the literature on
      this topic. METHODS AND MATERIALS: Personal files of patients treated for
      secondary intracranial meningioma during a 31-year period were reviewed. In cases
      which met the criteria for radiation-induced tumors, steroid hormone receptor and
      Ki-67 status were analyzed. For the literature review, computerized database
      systems and reference lists from respective publications were used. RESULTS: Five
      patients (2 females, 3 males), 3-11 years old at the time of cranial irradiation,
      developed secondary meningioma after a latency period of 9.5-31.5 years. Three
      patients had multiple tumors and 2 developed recurrent disease. Of 9
      histologically examined tumors, 5 were graded as benign and 4 as atypical
      meningiomas, with Ki-67 proliferative index 3.2 +/- 3.6 and 10 +/- 6,
      respectively. The ratio between positive and negative meningiomas regarding
      immunostaining for progesterone and estrogen receptors was eight-to-one and six
      to-three, respectively. Cumulative actuarial risk of secondary meningioma in a
      cohort of 445 children 16 years or younger treated with high-dose cranial
      irradiation between 1968 and 1990 in Slovenia at 10, 20, and 25 years was 0.53%,
      1.2%, and 8.18%, respectively. Out of 126 cases of radiation-induced meningiomas
      reported, 57% were females and 43% were males, with mean age at presentation 33
      +/- 17.3 years. The majority (68%) of patients was irradiated during childhood.
      The latency period was significantly shorter in those who aged 5 years or less at
      the time of cranial irradiation (p = 0.04), and in those with atypical/anaplastic
      tumor (p = 0.01). Correlation between radiation dose and latency period could not
      be found. CONCLUSION: Secondary meningiomas following high-dose cranial
      irradiation are characterized by younger age at presentation, by higher male-to
      female ratio and by biologically more aggressive variants compared to primary
      spontaneous meningiomas. Latency period correlated with the age at the time of
      cranial irradiation and with tumor grade but not with irradiation dose. Ki-67
      immunoreactivity correlated with histological grade. The progesterone and
      estrogen receptor immunoreactivity was high. The risk for development of
      secondary meningioma after high-dose cranial irradiation was increasing with the
      time of follow-up.

PMID- 10924974
TI  - Risk factors for neurological complications after acoustic neurinoma
      radiosurgery: refinement from further experiences.
AB  - PURPOSE: Further actuarial analyses of neurological complications were performed
      on a larger population treated by stereotactic radiosurgery at our institution,
      to establish the optimal treatment parameters. METHODS AND MATERIALS: Between
      June 1990 and September 1998, 138 patients with acoustic neurinomas underwent
      stereotactic radiosurgery at Tokyo University Hospital. Of these, 125 patients
      who received medical follow-up for 6 months or more entered the present study.
      Patient ages ranged from 13 to 77 years (median, 53 years). Average tumor
      diameter ranged from 6.7 to 25.4 mm (mean, 13. 9 mm). Maximum tumor doses ranged
      from 20 to 40 Gy (mean, 29.8 Gy) and peripheral doses from 12 to 25 Gy (mean,
      15.4 Gy). One to 12 isocenters were used (median, 4). Follow-up period ranged
      from 6 to 104 months (median, 37 months). The potential risk factors for
      neurological complications were analyzed by two univariate and one multivariate
      actuarial analyses. Neurological complications examined include hearing loss,
      facial palsy, and trigeminal nerve dysfunction. Variables included in the
      analyses were four demographic variables, two variables concerning tumor
      dimensions, and four variables concerning treatment parameters. A variable with
      significant p values (p < 0.05) on all three actuarial analyses was considered a
      risk factor. RESULTS: The variables that had significant correlation to
      increasing the risk for each neurological complication were: Neurofibromatosis
      Type 2 (NF2) for both total hearing loss and pure tone threshold (PTA) elevation;
      history of prior surgical resection, tumor size, and the peripheral tumor dose
      for facial palsy; and the peripheral tumor dose and gender (being female) for
      trigeminal neuropathy. In facial palsies caused by radiosurgery, discrepancy
      between the course of palsy and electrophysiological responses was noted.
      CONCLUSION: Risk factors for neurological complications seem to have been almost
      established, without large differences between institutions treating a large
      number of patients by radiosurgery. Radiosurgical doses and tumor dimensions were
      considered the two important risk factors for the 7th and 5th nerve injuries.
      Neurofibromatosis Type 2 was an important factor for hearing loss.

PMID- 10924975
TI  - The deep inspiration breath-hold technique in the treatment of inoperable non
      small-cell lung cancer.
AB  - PURPOSE: Conventional radiotherapeutic techniques are associated with lung
      toxicity that limits the treatment dose. Motion of the tumor during treatment
      requires the use of large safety margins that affect the feasibility of
      treatment. To address the control of tumor motion and decrease the volume of
      normal lung irradiated, we investigated the use of three-dimensional conformal
      radiation therapy (3D-CRT) in conjunction with the deep inspiration breath-hold
      (DIBH) technique. METHODS AND MATERIALS: In the DIBH technique, the patient is
      initially maintained at quiet tidal breathing, followed by a deep inspiration, a
      deep expiration, a second deep inspiration, and breath-hold. At this point the
      patient is at approximately 100% vital capacity, and simulation, verification,
      and treatment take place during this phase of breath-holding. RESULTS: Seven
      patients have received a total of 164 treatment sessions and have tolerated the
      technique well. The estimated normal tissue complication probabilities decreased
      in all patients at their prescribed dose when compared to free breathing. The
      dose to which patients could be treated with DIBH increased on average from 69.4
      Gy to 87.9 Gy, without increasing the risk of toxicity. CONCLUSIONS: The DIBH
      technique provides an advantage to conventional free-breathing treatment by
      decreasing lung density, reducing normal safety margins, and enabling more
      accurate treatment. These improvements contribute to the effective exclusion of
      normal lung tissue from the high-dose region and permit the use of higher
      treatment doses without increased risks of toxicity.

PMID- 10924976
TI  - Factors predicting severe radiation pneumonitis in patients receiving definitive
      chemoradiation for lung cancer.
AB  - PURPOSE: To identify factors that may predict for severe radiation pneumonitis or
      pneumonopathy (RP), we reviewed a set of simple, commonly available
      characteristics. METHODS AND MATERIALS: Medical records of 148 lung cancer
      patients with good performance status (ECOG 0-1) treated definitively with
      chemoradiation from 6/92-6/98 at the University of Pennsylvania were reviewed.
      Actuarial survival and the crude rate of severe radiation pneumonitis were
      determined as a function of several variables. Potential predictive factors
      examined included age, gender, histology, stage, pulmonary function, performance
      status (0 vs. 1), weight loss, tumor location, radiation dose, initial radiation
      field size, chemotherapy regimen, and timing of chemotherapy. Univariate analysis
      (log-rank test) was performed for each variable. Multivariate analysis was
      performed using linear regression. RESULTS: Median survival for the entire cohort
      was 14.7 months. Four patients were inevaluable for pneumonitis due to early
      death from progressive disease. Of the remaining 144 evaluable patients, 12
      (8.3%) experienced severe RP. The most significant factor predicting for severe
      RP was performance status (p < 0.003). The risk of severe RP was 16% for PS-1
      patients vs. 2% for PS-0 patients. Women were significantly more likely to
      develop severe RP than men (p = 0.01). Among 67 patients for whom pre-radiation
      therapy pulmonary function data were available, forced expiratory volume of the
      lung in 1 second (FEV(1)) was also significant (p = 0. 03). No patient suffering
      severe RP had a pretreatment FEV(1) > 2.0 liters. The median radiation dose was
      59.2 Gy and median initial radiation field size was 228 cm(2). Neither
      radiotherapy factor predicted for RP. Other factors studied, including
      chemotherapy drugs, and schedule, also were not significant predictors of severe
      RP. CONCLUSIONS: Pretreatment performance status, gender, and FEV(1) are
      significant predictors of severe radiation pneumonopathy, at least when using
      conventional radiation fields and doses. Complex radiation dose-volume algorithms
      that attempt to predict lung complication probabilities should probably
      incorporate these simply obtained clinical parameters.

PMID- 10924977
TI  - A palliative accelerated irradiation regimen for advanced non-small-cell lung
      cancer vs. conventionally fractionated 60 GY: results of a randomized equivalence
      study.
AB  - PURPOSE: Radiation oncologists are often faced with patients with advanced non
      small-cell lung cancer (NSCLC), who are not suitable candidates for state-of-the
      art radical treatment, but who also are not judged to have a very short life
      expectancy. Some physicians treat these patients palliatively, whereas others
      advocate more intensive treatment. To find out if there is a substantial
      difference in outcome between these approaches, we performed a randomized
      prospective study. METHODS AND MATERIALS: Between 1994 and 1998, 152 eligible
      patients with advanced NSCLC Stage III (n = 121) or minimal Stage IV (n = 31)
      were randomized to receive conventionally fractionated (cf; A: 60 Gy, 6 weeks, n
      = 79) or short-term treatment (PAIR; B: 32 Gy, 2 Gy b.i.d.; n = 73) of tumor and
      mediastinum. RESULTS: One-year survival rate for all patients was 37% with no
      significant difference between the two treatment arms (A: 36%; B: 38%; p = 0.76).
      As far as can be judged from limited data available, palliation was adequate and
      similar for the two treatment arms. Apart from expected differences in the time
      course of esophagitis, acute side effects were moderate and equally distributed.
      No severe late effects were observed. CONCLUSIONS: In the present randomized
      trial, survival and available data on palliation were not different after cf to
      60 Gy compared to the palliative PAIR regimen. Therefore, for patients who are
      not suitable for radical treatment approaches, the prescription of a palliative
      short-term irradiation appears preferable compared to cf over several weeks.

PMID- 10924978
TI  - Respiratory-induced prostate motion: quantification and characterization.
AB  - PURPOSE: The precise localization of the prostate is critical for dose-escalated
      conformal radiotherapy. This study identifies and characterizes a potential cause
      of inaccurate prostatic localization-respiratory-induced movement. METHODS AND
      MATERIALS: Prostate movement during respiration was measured fluoroscopically
      using implanted gold fiducial markers. Twenty sequential patients with CT(1)-T(3)
      N(0) M(0) prostate carcinoma were evaluated prone, immobilized in customized
      thermoplastic shells. A second 20 patients were evaluated both prone (with and
      without their thermoplastic shells) and supine (without their shells). RESULTS:
      When the patients were immobilized prone in thermoplastic shells, the prostate
      moved synchronously with respiration. In the study the prostate was displaced a
      mean distance of 3.3 +/- 1.8 (SD) mm (range, 1-10.2 mm), with 23% (9/40) of the
      displacements being 4 mm or greater. The respiratory-associated prostate movement
      decreased significantly when the thermoplastic shells were removed. CONCLUSION:
      Significant prostate movement can be induced by respiration when patients are
      immobilized in thermoplastic shells. This movement presumably is related to
      transmitted intraabdominal pressure within the confined space of the shells.
      Careful attention to the details of immobilization and to the possibility of
      respiratory-induced prostate movements is important when employing small field
      margins in prostatic radiotherapy.

PMID- 10924979
TI  - Failure-free survival following brachytherapy alone or external beam irradiation
      alone for T1-2 prostate tumors in 2222 patients: results from a single practice.
AB  - PURPOSE: To evaluate failure-free survival (FFS) for brachytherapy (BT) alone
      compared to external beam radiotherapy (EBRT) alone for Stage T1-2 Nx-No Mo
      patients over the same time period by a single community-based practice in the
      prostate-specific antigen (PSA) era. MATERIALS AND METHODS: The database of
      Arizona Oncology Services (a multiphysician radiation oncology practice in the
      Phoenix metropolitan area) was reviewed for patients meeting the following
      criteria: (1) T1 or T2 Nx-No Mo prostate cancer; (2) no prior or concurrent
      therapy including hormones; (3) treatment period 12/88-12/95; and (4) treatment
      with either EBRT alone or BT alone ((125)I or (103)Pd). This yielded 1527 EBRT
      and 695 BT patients; no patients meeting the above criteria were excluded from
      analysis. Median follow-up for EBRT patients was 41.3 months and, for BT
      patients, 51.3 months. Patients were not randomized to either therapy but rather
      received EBRT or BT based upon patient, treating, and/or referring physician
      preference. PSA failure was defined according to the ASTRO consensus guidelines.
      The median patient age was 74 years for both groups. RESULTS: Failure-free
      survival at 5 years for EBRT and BT are 69% and 71%, respectively (p = 0.91). For
      T stage, no significant difference in FFS at 5 years is observed between EBRT and
      BT for either T1 (78% vs. 83%, p = 0.47) or T2 (67% vs. 67%, p = 0.89) tumors.
      Analysis by Gleason score shows superior outcomes for Gleason 8-10 lesions
      treated with EBRT vs. BT (5-year FFS 52% vs. 28%, p = 0.04); outcomes for lower
      grade lesions (Gleason 4-6) when analyzed by Gleason score alone do not
      significantly differ according to treatment received. Patients with initial PSA
      values of 10-20 ng/dL have an improved FFS with EBRT vs. BT at 5 years (70% vs.
      53%, p = 0.001); outcomes for patients with initial PSA ranges of 0-4 ng/dL, of >
      4-10 ng/dL, and > 20 ng/dL did not differ significantly by treatment received.
      FFS was also determined for presenting Gleason score/PSA combinations; all
      Gleason combinations in the initial PSA range >10-20 ng/dL had superior outcomes
      with EBRT compared to BT, and this reached statistical significance for Gleason
      scores of 2-4 (72% vs. 58%, p = 0.026), Gleason 7 (67% vs. 28%, p = 0.002), and
      Gleason 8-10 (63% vs. 23%, p = 0.05). CONCLUSION: In our patient population,
      either EBRT or BT appear equally efficacious for patients with T1/T2 disease with
      Gleason scores </= 6 or PSA </= 10 ng/dL. Patients with presenting Gleason scores
      of 8-10 or PSA > 10 ng/dL (but </= 20 ng/dL) appear to fare significantly worse
      with BT alone compared to EBRT alone. Neither EBRT nor BT alone was particularly
      effective for patients with a presenting PSA > 20 ng/dL, as would be anticipated
      from the significant risks of occult distant metastasis in this group. To our
      knowledge, this is the first report comparing the outcome of EBRT and BT
      treatment in patients treated concurrently by a single group, and these results,
      achieved in a community-based practice, compare favorably to data from academic
      centers regarding external beam, brachytherapy, or surgical outcomes and should
      be generalizable to the community at large.

PMID- 10924980
TI  - Rectal complications associated with transperineal interstitial brachytherapy for
      prostate cancer.
AB  - PURPOSE: As transperineal interstitial permanent prostate brachytherapy (TIPPB)
      grows in acceptance as an option in the treatment of organ-confined prostate
      cancer, its associated toxicities are being defined. This clinical report
      documents rectal toxicity from a large cohort of men treated by a single
      practitioner for adenocarcinoma of the prostate. METHODS AND MATERIALS: Eight
      hundred twenty-five men were treated from September 1992 to September 1998 with
      TIPPB. One hundred-forty were treated in conjunction with external beam
      irradiation (EBRT) and 685 with TIPPB alone. All patients were implanted under
      real-time ultrasound guidance. No dose-volume histogram analysis was performed
      for this study. All patients were followed at 5 weeks after the procedure, then
      every 3-6 months thereafter. Rectal morbidity was graded by a modified RTOG
      toxicity scale. Therapy to control symptoms was recommended on an individual
      basis. RESULTS: The median follow-up for the cohort is 48 months. A total of 77
      patients (9.4%) reported Grade 1 toxicity at some time following an implant
      whereas 54 patients (6.6%) reported Grade 2 toxicity. The peak post-TIPPB time
      for experiencing rectal toxicity was 8 months at which time Grade 1 and 2 rectal
      toxicity was reported in 9.5% of the patients. This improved over the subsequent
      months and resolved in all patients by 312 years. Four patients (0.5%) reported
      Grade 3 rectal toxicity with rectal ulceration identified on colonoscopy at 1
      year from implant. Two of the four patients had colonic manipulation in the
      radiated portion of the colon which subsequently caused it to bleed. None of the
      patients required blood product transfusion. In 3 of the 4 patients the Grade 3
      rectal toxicity has resolved spontaneously and 1 patient continues to heal at the
      time of this report. No patient required hospitalization or surgical
      intervention. CONCLUSION: TIPPB is a tolerable and acceptable treatment option
      when used alone in early-stage, organ-confined adenocarcinoma of the prostate and
      in conjunction with EBRT in more advanced disease. This clinical report adds to
      the growing literature regarding the potential morbidity associated with this
      procedure and indicates that serious rectal injury is rare.

PMID- 10924981
TI  - Is radiation alone adequate treatment to the axilla for patients with limited
      axillary surgery? Implications for treatment after a positive sentinel node
      biopsy.
AB  - PURPOSE: To estimate the possible efficacy of axillary radiation therapy (AXRT)
      following a positive sentinel node biopsy (SNB), we evaluated the risk of
      regional nodal failure (RNF) for patients with clinical Stage I or II, clinically
      node-negative invasive breast cancer treated with either no dissection or a
      limited dissection (LD) defined as removal of 5 nodes or less followed by AXRT.
      MATERIALS AND METHODS: From 1978 to 1987, 292 patients underwent AXRT in the
      absence of axillary dissection; 126 underwent AXRT following LD. The median dose
      to the axilla was 46 Gy. The median dose to the supraclavicular fossa was 45 Gy.
      Among patients found to have positive nodes on LD, adjuvant chemotherapy and
      tamoxifen were administered to 81% and 7% of subjects, respectively. All patients
      had potential 8-year follow-up. RESULTS: Six of the 418 patients (1. 4%)
      developed RNF as a first site of failure within 8 years. Among these 6 patients
      (1.4%) with RNF as the first site of failure, 4 had simultaneous distant and
      regional recurrences; and 2 had isolated axillary failures. Three of the 292
      patients (1%) with no axillary dissection, none of 84 patients with
      pathologically negative nodes and 3 of 42 patients (7%) with pathologically
      involved nodes had RNF as a first site of failure. Radiation pneumonitis
      developed in 5 patients (1.2%), brachial plexopathy in 5 (1.2%) and arm edema in
      4 (1.2%). In all cases, radiation pneumonitis and brachial plexopathy were
      transient. CONCLUSION: These results imply that AXRT may be an effective and safe
      alternative to completion dissection for treatment of the axilla following a
      positive SNB. Further studies comparing these two options in specific patient
      subgroups are needed.

PMID- 10924982
TI  - The relationship between lymphatic vessell invasion, tumor size, and pathologic
      nodal status: can we predict who can avoid a third field in the absence of
      axillary dissection?
AB  - PURPOSE: Tangential (2-field) radiation therapy to the breast and lower axilla is
      typically used in our institution for treating patients with early-stage breast
      cancer who have 0-3 positive axillary nodes, as determined by axillary
      dissection, whereas a third supraclavicular/axillary field is added for patients
      with 4 or more positive nodes. However, dissection may result in complications
      and added expense. We, therefore, assessed whether clinical or pathologic factors
      of the primary tumor could reliably predict, in the absence of an axillary
      dissection, which patients with clinically negative axillary nodes have such
      limited pathologic nodal involvement that they might be effectively treated with
      only tangential fields. This would eliminate both the complications of axillary
      dissection and the added complexity and potential morbidity of a
      supraclavicular/axillary field. METHODS AND MATERIALS: In this study, 722 women
      with clinical Stage I or II unilateral invasive breast cancer of infiltrating
      ductal histology, with clinically negative axillary nodes, at least 6 lymph nodes
      recovered on axillary dissection, and central pathology review were treated with
      breast-conserving therapy from 1968 to 1987. Pathologic nodal status was assessed
      in relation to clinical T stage, the presence of lymphatic vessel invasion (LVI),
      age, histologic grade, and the location of the primary tumor. RESULTS: LVI, T
      stage, and tumor location were each significantly correlated with nodal status on
      univariate analysis. Ninety-seven percent of LVI-negative patients had 0-3
      positive axillary nodes compared to 87% of LVI-positive patients. There was no
      association between T stage and extent of axillary involvement within LVI
      negative and LVI-positive subgroups. In a logistic regression model, only LVI
      remained a significant predictor of having 4 or more positive nodes, although
      tumor size was of borderline significance. The odds ratio for LVI (positive vs.
      negative) as a predictor of having 4 or more positive nodes was 3.9 (95% CI, 2.0
      7.6). CONCLUSION: For patients with clinical T1-2, N0, infiltrating ductal
      carcinomas, the presence of LVI is predictive of having 4 or more positive
      axillary nodes. Only 3% of patients with clinical T1-2, N0, LVI-negative breast
      cancers had 4 or more positive nodes on axillary dissection. Such patients may be
      reasonable candidates for treatment with tangential radiation fields in the
      absence of axillary dissection.

PMID- 10924983
TI  - Internal mammary node coverage: an investigation of presently accepted
      techniques.
AB  - PURPOSE: Recent publications have generated a renewed interest in regional nodal
      treatment to include the ipsilateral supraclavicular and internal mammary nodes
      (IMN). The purpose of this study is to evaluate three presently accepted
      treatment techniques for coverage of the intact breast and ipsilateral lymph node
      regions and to construct recommendations regarding the utilization of these
      techniques. METHODS AND MATERIALS: Anatomic data were obtained from five randomly
      selected patients with computerized tomography (CT) in treatment position. Three
      patients presented with cancer of the left breast and two with cancer of the
      right. Using the Pinnacle 3-D planning system, normal tissue volumes of breast,
      ipsilateral lung, heart, sternum, and the IMN target were delineated for each
      patient. Three accepted techniques used to treat ipsilateral breast, internal
      mammary and supraclavicular nodes (extended tangents, 5-field, partly wide
      tangents) were configured and compared to a supraclavicular field matched to
      standard tangential fields. A dosage of 50 Gy in 25 fractions was prescribed to
      the target volume. Dose-volume histograms (DVH) were generated and analyzed with
      regard to target volume coverage and lung/heart volumes treated. RESULTS: All of
      the treatment techniques covering IMN include at least 10% more lung and heart
      volume than that covered by standard tangential fields. The relative lung and
      heart volumes treated with each technique were consistent from patient to
      patient. The 5-field technique clearly treats the largest volume of normal
      tissue; however, most of this volume receives less than 50% of the dose
      prescribed. The percent of heart and ipsilateral lung treated to 20 Gy, 30 Gy,
      and 40 Gy have been calculated and compared. Due to the increase in chest wall
      thickness and depth of IMN superiorly, complete coverage was not achieved with
      any technique if the IMN target extended superiorly into the medial
      supraclavicular field where dose fall-off resulted in a significant underdosing
      at depth. For the same anatomic reasons, the 5-field technique underdosed 10-15%
      of the IMN target volume in 4 of the 5 cases. This technique also yielded a
      greater dose heterogeneity, which was not seen with the other techniques
      evaluated and correlated with the change of anterior chest wall thickness.
      CONCLUSIONS: Anatomic variation in chest wall thickness and IMN depth strongly
      suggests the routine use of multislice CT planning to ensure complete coverage of
      the target volume and optimal sparing of normal tissue. All of the techniques can
      be constructed to look acceptable at central axis. To cover the superior most
      aspect of the IMN chain either high tangential fields, a supraclavicular field
      photon beam of energy >6 MV, or an AP/PA supraclavicular setup should be
      considered. The 5-field technique has the most difficulty in compensating for the
      increased depth of the IMN in the superior aspect of the tangent fields with up
      to +/-40% variation of the dose noted in isolated areas within the target volume.
      Based on our evaluation, the partly wide tangent technique offers many
      advantages. It provides optimal coverage of the target volume, reduces coverage
      of normal tissue volumes to an acceptable level, and is easily reproducible with
      a high degree of dose homogeneity throughout the target.

PMID- 10924984
TI  - Comparison of standard and individually planned infradiaphragmatic fields in
      irradiation of retroperitoneal lymph nodes.
AB  - PURPOSE: In prophylactic irradiation of infradiaphragmatic lymphatic nodes (LN),
      the width of the paraaortic and pelvic field is given by a line joining the tips
      of the transverse processes of the 11th thoracic to the 4th lumbar vertebrae.
      Then the field boundary follows a straight line to the most lateral point of the
      acetabulum seen on the simulation film. Another method of setting the field
      border is to project the lateral contours of the large abdominal vessels from
      T(1)-weighted coronal MR images of the abdomen onto the simulator radiographs and
      add a 2-cm margin along the so delineated vessels. In our study, we compared both
      methods as to full enclosure of paraaortic and pelvic lymphatics or nodal miss.
      MATERIAL AND METHODS: Abdominal CT scans of 81 patients with involvement of
      paraaortic lymph node regions with LN sizes not exceeding 2.5 cm were examined.
      The distance from the center of the appropriate vertebra to the center of the
      most lateral lymph node was referred to the transverse process as well as to the
      outside contour of the aorta on the left and the vena cava on the right side.
      Respectively, the LN were measured referenced to the iliac vessels from the 5th
      lumbar through to the 2nd sacral vertebra. At the level of the hip joint the
      distance was measured from the midline as determined by a line through the center
      of the sacrum, perpendicular to a line connecting center of both femoral heads.
      RESULTS: Our measurements showed that lymph nodes do occur (1) lateral to the
      transverse processes of the thoracic and lumbar vertebrae as well as (2) outside
      the 2-cm safety margin from the lateral contour of the large abdominal vessels.
      CONCLUSION: These data clearly show that the traditional fields for radiation of
      infradiaphragmatic lymphatic nodes have not been large enough to enclose almost
      all retroperitoneal and pelvic lymph nodes with certainty. We recommend an
      expansion of the fields.

PMID- 10924985
TI  - Head-and-neck stages I and II extranodal non-Hodgkin's lymphomas: real
      classification and selection for treatment modality.
AB  - PURPOSE: We re-evaluated histopathological specimens of head and neck early-stage
      extranodal non-Hodgkin's lymphoma (NHL) using the revised European and American
      lymphoma (REAL) classification, and also investigated the relationship between
      the clinical characteristics and histopathological classification in an attempt
      to evaluate the usefulness of this new classification system in selecting
      treatment modalities. MATERIALS AND METHODS: Between 1979 and 1995, 117 patients
      with histologically confirmed stages I and II NHL of head-and-neck extranodal
      regions were treated. Of these patients, 110 specimens were available for re
      evaluation. Sixty-four patients had Stage I, and 46 had Stage II diseases. All
      but 3 had received radiation therapy, and 59 patients were also treated with
      intensive combination chemotherapy. RESULTS: There were 32 extranodal marginal
      zone B-cell lymphomas, 57 diffuse large B-cell lymphomas, 11 peripheral T/NK-cell
      lymphomas, and 10 others. The 5- and 10-year cause-specific survival rates for
      all patients were 72% and 62%, respectively. Patients with extranodal marginal
      zone B-cell lymphoma or other low-grade B-cell lymphomas demonstrated higher
      survival rates than patients with other lymphomas. Patients with peripheral T/NK
      lymphomas showed the lowest survival rate. CONCLUSION: The REAL classification
      accurately indicated the prognosis of patients with NHL. These results suggest
      that appropriate treatment modalities can be selected using this classification.

PMID- 10924986
TI  - Tumor bulk as a prognostic factor for the management of localized aggressive non
      Hodgkin's lymphoma: a survey of the Japan Lymphoma Radiation Therapy Group.
AB  - PURPOSE: To identify the prognostic factors that specifically predict survival
      rates of patients with localized aggressive non-Hodgkin's lymphoma (NHL). METHODS
      AND MATERIALS: The survey was carried out at 25 radiation oncology institutions
      in Japan in 1998. The 5-year event-free (EFS) and overall survival rates (OAS)
      were calculated, and univariate and multivariate analyses were done to identify
      which of the following factors, namely, gender, age, performance status (PS),
      serum lactate dehydrogenase (LDH) level, Stage (I vs. II), tumor bulk (maximum
      diameter), and treatment, were significant from the viewpoint of prognosis.
      RESULTS: A total of 1141 patients with Stage I and II NHL were treated by the
      Japanese Lymphoma Radiation Therapy Group between 1988 and 1992. Of them, 787
      patients, who were treated using definitive radiotherapy with or without
      chemotherapy for intermediate- and high-grade lymphomas in working formulation,
      constituted the core of this study. Primary tumors arose mainly from extranodal
      organs (71%) in the head and neck (Waldeyer's ring: 36% and sinonasal cavities:
      9%). The factors associated with poorer prognosis were age over 60 years old (p <
      0. 0001), radiation therapy alone (p < 0.0001), PS = 2-4 (p = 0.0011), (sex male,
      p = 0.0078), a bulky tumor more than 6 cm in maximum diameter (p = 0.0088),
      elevated LDH (p = 0.0117), and stage II (p = 0.0642). A median dose of 42 Gy was
      delivered mainly to the involved fields. Short-course chemotherapy was provided
      in 549 (70%) patients. The 5-year OAS and EFS rates for all patients were 71% and
      67%, respectively. According to the stage-modified International Prognostic
      Index, the 5-year EFS of the patients with risk factors from 0 to 1 was 76%, 61%
      for patients with two risk factors, and 26% for patients with three or more risk
      factors. CONCLUSION: Extranodal presentation, especially Waldeyer's ring and
      sinonasal cavities, is encountered more frequently in Japan than in Western
      countries. Tumor bulk is an important prognostic factor in patients with
      localized aggressive extranodal NHL. Short course chemotherapy followed by
      radiation therapy was associated with prolonged survival in patients with
      localized aggressive NHLs of extranodal origin and 0-1 risk factor.

PMID- 10924987
TI  - The need for long-term surveillance for patients treated with curative
      radiotherapy for Hodgkin's disease: University of Minnesota experience.
AB  - PURPOSE: To examine the long-term outcome of Stage I, II, and III patients
      treated with curative radiotherapy for Hodgkin's disease at the University of
      Minnesota Hospital, with particular focus on long-term treatment-related
      complications and the need for long-term surveillance after treatment. METHODS
      AND MATERIALS: A total of 210 Stage I, II, and III patients (98 female, 112 male)
      treated at the University of Minnesota since 1970 were included in this study.
      All patients were laparotomy staged. Between 1970 and 1974, 35 high-risk patients
      (i.e., patients with large mediastinal mass, and/or hilar disease, and/or splenic
      involvement) and 40 low-risk patients were treated with standard field
      radiotherapy. From 1975 on, 67 high-risk patients received radical radiotherapy
      because of poor outcomes with standard radiotherapy, and 68 low-risk patients
      received standard radiotherapy. Salvage chemotherapy was given to 62 patients who
      recurred. Median follow-up for all patients was 15.6 years (range 0. 35-26.5
      years). Long-term complications after treatment were assessed using standardized
      incidence ratios (SIR) and mortality ratios (SMR), with particular focus on
      cardiac complications and secondary malignancies. RESULTS: By study end, 70% of
      the patients are alive and 70% had never recurred. Complications included 33
      second malignancies and 75 cardiovascular events. Patients treated for Hodgkin's
      disease had about 7 times the risk of dying from cardiac problems (SMR = 7.2) and
      10 times the risk of dying from a second malignancy (SMR = 10.3) compared to the
      general population. In terms of absolute risk, Hodgkin's disease would cause
      seven additional deaths from secondary malignancies per year among 1000 patients
      and four additional deaths from cardiac problems. CONCLUSION: Hodgkin's disease
      patients treated successfully with radiotherapy are at an increased risk for
      developing long-term treatment-related cardiac disease and/or second
      malignancies. Careful monitoring of these patients is essential to manage
      morbidity and minimize mortality from these complications. Suggestions for the
      establishment of worldwide surveillance programs for these patients are proposed.

PMID- 10924988
TI  - Subclinical thyroid disease after radiation therapy detected by radionuclide
      scanning.
AB  - PURPOSE: The actuarial risk for developing benign or malignant thyroid disease
      following radiation therapy (RT) is controversial, but may be as high as 50% at
      20 years. An effective screening modality should be specific but not overly
      sensitive, a limitation of ultrasound. We questioned whether Technetium-99 m
      pertechnetate ((99m)Tc TcO(4)(-)) scanning could detect clinically significant
      disease in ostensibly disease-free cancer survivors. METHODS AND MATERIALS:
      Eligibility criteria included an interval of at least 5 years after RT to the
      cervical region, a thyroid gland that was normal to palpation, euthyroid status
      determined by clinical examination, free T4 and TSH. The 34 patients scanned
      included 16 children (<18 years old) and 18 adults at the time of RT, 16 females
      and 18 males. The mean age at RT was 20 years (range, 2.1-50.3 years), and the
      mean age at (99m)Tc TcO(4)-scanning was 33 years (range, 13.6-58 years),
      providing a mean interval of 13 years (range, 5.3-26.6 years). The mean RT dose
      to the thyroid was 36.4 Gy (range, 19.5-52.5). Thyroid scanning was performed
      with a 5 mCi dose of (99m)Tc TcO(4)(-) obtaining flow, immediate and delayed
      static, and pinhole collimator images. RESULTS: Seven patients (21.6%) had
      abnormal scans, and the percentage was higher among children (25%) and females
      (25%) compared to adults (16.7%) and males (16.7%), respectively. Two of 34
      patients (5.9%) were discovered to have a thyroid cancer; histopathologies were
      papillary and follicular carcinoma. CONCLUSION: In this population of clinically
      normal cancer survivors who had been irradiated to the cervical region,
      subclinical thyroid disease, of potential clinical significance, was detected by
      (99m)Tc TcO(4)(-) in about 20%. Children may be more commonly affected. Although
      the cost effectiveness of screening will require a larger sample number, we
      propose a surveillance schema for this patient population.

PMID- 10924989
TI  - Impact on treatment outcome and late effects of customized treatment planning in
      cervix carcinomas: baseline results to compare new strategies.
AB  - PURPOSE: The aim of the study was to determine the predictive factors of
      complications, to evaluate the impact of customized treatment planning on late
      normal tissue effects per stage, and to report disease-free survival (DFS) and
      local control (LC) rates. METHODS AND MATERIALS: From 1970 to 1994, 642 patients
      were treated with radiotherapy alone for carcinoma of the intact uterine cervix.
      According to the International Federation of Gynecology and Obstetrics (FIGO)
      substaging, 34% were Stage I, 39% Stage II, and 27% Stage III. The analysis was
      divided into three periods: 1970-1978 (use of standard prescriptions),1979-1984
      (implementation of individual adjustments), 1985-1994 (systematic individual
      adjustments). Five-year DFS, LC, and complications rates were calculated using
      the Kaplan-Meier method. Predictive factors of complications were determined by
      univariate analysis using frequency tables and nonparametric t-tests.
      Multivariate analysis consisted of a polychotomous stepwise regression. RESULTS:
      The comparison of the three time periods showed a significant reduction of the
      external radiation dose (dose above 40 Gy in 47% of patients before 1979 vs. 36%
      after 1984), of the use of parametrial boost (55% vs. 39%), of the use of vaginal
      cylinder (28% vs. 11.5%), and of the HWT volume (combined intracavitary and
      external irradiation) (842 cc vs. 503 cc on average). The total
      sequelae/complications rate, all toxicity grades, all stages, all organs was 51%.
      Five-year actuarial rate per toxicity grade was: G1, 42%; G2, 23.5%; G3, 10%; G4,
      3%. The three main predictive factors for rectal and bladder
      sequelae/complications (all toxicity grades) taking into account time period
      were: the increase of external radiation dose, the high dose rate at reference
      points, and the whole vagina brachytherapy. No G4 occurred in the third period.
      The rate of G3 complications dropped from 16% to 6% over time: from 5% during the
      first period to 0% during the third period in Stage I, from 8% to 6% in Stage II,
      and from 23% to 12% in Stage III. G3 currently describes a variety of clinical
      situations with a different impact on quality of life which justifies further
      refinements of definitions of late effects. In our experience the severity of G3
      markedly decreased: less than one-third of G3 had a real impact on quality of
      life in the last period compared to more than two-thirds in the first period.
      Meanwhile, 5-year LC rates remained stable in Stages I and II, 91% and 85%
      respectively. Conversely they fell from 75% to 55% in Stage III, thus raising the
      problem of underdosage and/or more accurate staging with time. CONCLUSIONS:
      Customized treatment planning eradicated lethal complications and provided a
      significant decrease of G3 in all stages while maintaining high cure rates in
      early stages. Dose reduction should be considered with caution in Stage III.

PMID- 10924990
TI  - The American Brachytherapy Society recommendations for high-dose-rate
      brachytherapy for carcinoma of the cervix.
AB  - PURPOSE: This report presents guidelines for using high-dose-rate (HDR)
      brachytherapy in the management of patients with cervical cancer, taking into
      consideration the current availability of resources in most institutions.
      METHODS: Members of the American Brachytherapy Society (ABS) with expertise in
      HDR brachytherapy for cervical cancer performed a literature review, supplemented
      their clinical experience to formulate guidelines for HDR brachytherapy of
      cervical cancer. RESULTS: The ABS strongly recommends that definitive irradiation
      for cervical carcinoma must include brachytherapy as a component. Each
      institution should follow a consistent treatment policy when performing HDR
      brachytherapy, including complete documentation of treatment parameters and
      correlation with clinical outcome, such as pelvic control, survival, and
      complications. The goals are to treat Point A to at least a total low-dose-rate
      (LDR) equivalent of 80-85 Gy for early stage disease and 85-90 Gy for advanced
      stage. The pelvic sidewall dose recommendations are 50-55 Gy for early lesions
      and 55-65 Gy for advanced ones. The relative doses given by external beam
      radiation therapy (EBRT) vs. brachytherapy depend upon the initial volume of
      disease, the ability to displace the bladder and rectum, the degree of tumor
      regression during pelvic irradiation, and institutional preference. As with LDR
      brachytherapy, every attempt should be made to keep the bladder and rectal doses
      below 80 Gy and 75 Gy LDR equivalent doses, respectively. Interstitial
      brachytherapy should be considered for patients with disease that cannot be
      optimally encompassed by intracavitary brachytherapy. While recognizing that many
      efficacious HDR fractionation schedules exist, some suggested dose and
      fractionation schemes for combining the EBRT with HDR brachytherapy for each
      stage of disease are presented. These recommendations are intended only as
      guidelines, and the suggested fractionation schemes have not been thoroughly
      tested. The responsibility for the medical decisions ultimately rests with the
      treating radiation oncologist. CONCLUSION: Guidelines are established for HDR
      brachytherapy for cervical cancer. Practitioners and cooperative groups are
      encouraged to use these guidelines to formulate their treatment and dose
      reporting policies. These guidelines will be modified, as image-based treatment
      becomes more widely available.

PMID- 10924991
TI  - Long-term impact of postoperative radiotherapy in carcinoma of the vulva FIGO
      I/II.
AB  - PURPOSE: Between 1953 and 1978, postoperative radiotherapy was used as an
      adjuvant therapy for carcinoma of the vulva that had not been treated with
      radical vulvectomy. We evaluated long-term results and possible prognostic
      factors. METHODS AND MATERIALS: Ninety-two patients were treated. Surgical
      procedures were simple vulvectomy, electrocoagulation, or local excision.
      Radiotherapy doses to the vulva ranged from 0 to 90 Gy. All patients received
      radiotherapy to the inguinal lymph nodes, ranging from 30 to 60 Gy. Thirty-year
      retrospective follow-up was done evaluating the records and statistical survival
      rates. RESULTS: Five-year actuarial survival rates in T1 patients were 71% (77%
      cause-specific survival rate), for T2 patients 43% (48% cause-specific survival
      rate). The difference between T1 and T2 patients was significant (p < 0.05).
      Patients with tumors of the labia minora had a significantly higher survival rate
      than those with different sites affected. Doses of 45 Gy or more to the vulva
      were sufficient to increase the 5-year cause-specific survival rate from 55% to
      88%. The results in three subgroups were analyzed, group 1 having received
      electrocoagulation, but no radiotherapy of the vulva; group 2, local excision and
      doses of 40 Gy to the vulva; group 3, local excision and doses of 60 Gy to the
      vulva. There was a significant effect on 10-year cause-specific survival rates:
      48% in group 1, 11% in group 2, and 88% in group 3. In multivariate analysis, the
      significant independent factors were T classification, tumor sites and-with only
      marginal significance-radiation doses to the vulva. CONCLUSIONS: The prognosis in
      early vulva carcinoma after nonradical surgery primarily depends on T
      classification and the site of the primary tumor. With univariate analyses, the
      dose has a significant effect on survival. In multivariate analyses the dose is a
      marginal independent factor in the whole group of patients. After nonradical
      surgery of early vulva carcinoma, the vulva should be irradiated resulting in
      better long-term survival.

PMID- 10924992
TI  - High-dose-rate intraoperative brachytherapy for recurrent colorectal cancer.
AB  - PURPOSE: Management of locally recurrent colorectal adenocarcinoma represents a
      significant challenge. Many of these tumors adhere to or invade into vital pelvic
      structures rendering surgery or external beam radiotherapy (EBRT) as palliative
      treatment. Therefore, a treatment approach was developed to evaluate the role of
      high-dose-rate intraoperative brachytherapy (HDR-IORT) and surgery as a component
      of therapy in the management of locally recurrent colorectal cancer. This is an
      update of our preliminary report with longer follow-up and larger patient
      numbers. METHODS AND MATERIALS: Between January 1992 and September 1998, 74
      patients with locally recurrent rectal cancer were treated with surgery and HDR
      IORT. Additional EBRT was given to 29 patients, and 33 patients received 5
      fluorouracil based chemotherapy. All patients underwent complete gross resection,
      and 21 of 74 had positive microscopic margin. The dose of HDR-IORT ranged from 10
      to 18 Gy. RESULTS: With a median follow-up of 22 months, the 5-year local
      control, distant metastasis disease-free, disease-free, and overall survival
      rates were 39%, 39%, 23%, and 23%, respectively. The only predictor of improved
      local control was a negative margin of resection with a 5-year local control rate
      of 43%, compared to 26% in those with positive margin (p = 0.02). For overall
      survival, a negative microscopic margin (p = 0.04) and the use of IORT + EBRT (p
      = 0.04) were significant predictors of improved survival. The incidence of
      peripheral neuropathy was 16%. CONCLUSION: The results with HDR-IORT in this
      group of patients are encouraging. Further improvements in local and distant
      control are still needed.

PMID- 10924993
TI  - Extremity soft-tissue sarcomas selectively treated with surgery alone.
AB  - PURPOSE: This study determined local control (LC), freedom from distant
      recurrence (FFDR), overall survival (OS), and potential prognostic factors in 34
      adult patients with primary extremity or limb girdle soft-tissue sarcoma
      selectively managed with limb-conservation surgery alone. METHODS AND MATERIALS:
      The medical records of 34 patients who underwent surgery alone for localized soft
      tissue sarcoma of the extremity were reviewed. Median duration of follow-up in
      survivors was 55 months (range, 24-143). There were 13 (38%) females. Eighteen
      (53%) of the tumors were low-grade, 15 (44%) were superficial, 15 (44%) were
      small (5 cm or less), and 16 (47%) involved the distal extremity. RESULTS:
      Actuarial 5-year LC was 80%, FFDR was 86%, and OS was 82%. All recurrences (local
      and distant) were in patients with high-grade tumors; their 5-year LC was 60%,
      FFDR was 71%, and OS was 69%. In 2 patients, metastatic disease developed either
      concurrent with or after their local recurrence. Univariate analysis revealed
      better OS, FFDR, and LC for patients with low-grade tumors (p < 0.05). Female
      patients had significantly better FFDR and OS (p < 0.05). CONCLUSION: It is
      appropriate to consider withholding irradiation for selected patients with low
      grade tumors resected with negative margins if, in the event of a local failure,
      a function-preserving surgical salvage is anticipated. For patients with high
      grade sarcomas, the control of local and distant disease was not acceptable with
      limb-conservation surgery alone.

PMID- 10924994
TI  - Tumor hypoxia--a confounding or exploitable factor in interstitial brachytherapy?
      Effects of tissue trauma in an experimental rat tumor model.
AB  - PURPOSE: To evaluate the potential effects of tumor hypoxia induced by
      afterloading catheter implantation on the effectiveness of brachytherapy in a rat
      tumor model. METHODS AND MATERIALS: Afterloading catheters (4) were implanted in
      subcutaneously growing R1M rhabdomyosarcoma in female Wag/Rij rats. A
      MicroSelectron (Nucletron) was used for interstitial high-dose-rate irradiation
      ((192)Ir). Tumor oxygenation, perfusion, and cell survival were assessed by pO(2)
      histography (Eppendorf), Tc-99m injection, and excision assay, respectively.
      RESULTS: Tumor perfusion was markedly reduced at 1 h after catheter implantation
      (33.9 +/- 6.0% (SEM, n = 9) of control) and partly recovered after 5 h (61.5 +/-
      12.2%). At 24 h, the perfusion level reached control values (100.6 +/- 25.7%),
      but was highly variable with some of the tumors showing hardly any recovery at
      all. Tumor oxygenation showed a similar pattern, but with less recovery. Median
      pO(2) readings were 13.5, 1.2, and 5.3 mm Hg before and at 1 and 24 h after
      implantation, respectively (7 tumors). The percentages of pO(2) readings </= 2.5
      mm Hg were 18.9%, 55.6%, and 41.3% at these time points. The difference in cell
      survival after irradiation (10 Gy) at 1 or 24 h after implantation was compatible
      with a radiobiological oxygen effect. CONCLUSION: Implantation of brachytherapy
      afterloading catheters induces an increased level of hypoxia for several hours by
      disrupting tumor perfusion, causing both a modest degree of direct cell kill and
      a significant reduction of the radiation effect. This transient hypoxia might be
      exploited by combining irradiation with properly timed treatments targeting
      hypoxic cells.

PMID- 10924995
TI  - Relative biological effectiveness for cell-killing effect on various human cell
      lines irradiated with heavy-ion medical accelerator in Chiba (HIMAC) carbon-ion
      beams.
AB  - PURPOSE: To clarify the relative biological effectiveness (RBE) values of various
      human cell lines for carbon-ion beams with 2 different linear energy transfer
      (LET) beams and to investigate the relationship between the cell-killing effect
      and the biophysical characters, such as the chromosome number and the area of the
      cell nucleus, using qualitatively different kinds of radiations. METHODS AND
      MATERIALS: Sixteen different human cell lines were irradiated with carbon-ion
      beams, having 2 different LET values (LET(infinity) = 13.3 and approximately 77
      keV/microm), accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at
      National Institute of Radiological Sciences in Japan. Cell-killing effect was
      detected as reproductive cell death using a colony-formation assay. The number of
      chromosomes was observed in a metaphase spread using the conventional method. The
      area of the cell nucleus was calculated as an ellipse on photographs using a
      micrometer. RESULTS: The RBE values calculated by the D(10), which is determined
      as the dose (Gy) required to reduce the surviving fraction to 10%, relative to X
      rays, range from 1.06 to 1.33 for 13-keV/microm-beam and from 2.00 to 3. 01 for
      approximate 77-keV/microm-beam irradiation on each cell line. There was a good
      correlation in the D(10) values of each cell line between X-rays and carbon-ion
      beams. However, the D(10) values did not clearly depend on either the chromosome
      number or the area of the cell nuclei. CONCLUSION: The RBE values for HIMAC
      carbon-ion beams are consistent with previous reports using carbon-ion beams with
      the similar LET values, and the cellular radiosensitivity of different cell lines
      well correlate among different types of radiation.

PMID- 10924996
TI  - Change in radiosensitivity with fractionated-dose irradiation of carbon-ion beams
      in five different human cell lines.
AB  - PURPOSE: To investigate the change in the surviving fractions by fractionated
      dose irradiations with carbon ions, based on the recovery of potentially lethal
      damage (PLDR) and the change of radiosensitivity by every fractionated-dose
      irradiation. METHODS AND MATERIALS: One normal human and four human-tumor cell
      lines were used. Cells were irradiated with carbon ions accelerated by the Heavy
      Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological
      Sciences in Japan. The LET values were estimated to be 13.18 keV/microm for low
      LET beams and 76.92 +/- 0.20 keV/microm for high-LET beams. Fractionated-dose
      irradiations were carried out with 5 fractions within a 24-h interval. RESULTS:
      The surviving fractions for the fractionated-dose irradiation with X-rays and
      carbon ions decreased exponentially with increasing the number of fractions in
      the tumor cell lines. In contrast, the surviving fractions for the carbon ions in
      normal human cells decreased exponentially as well as the tumor cell lines, while
      it tended to level off from the 3rd to the 5th fraction in the case of using X
      rays. CONCLUSION: The change in both the recovery ratio of the PLDR and
      radiosensitivity by every fractionated-dose irradiation depends on individual
      cell lines and the quality of radiations.

PMID- 10924997
TI  - Radiobiological modeling and clinical trials.
AB  - PURPOSE: Standard clinical trial designs can lead to restrictive conclusions: the
      "best recommended treatments" based on trial results, although generally
      applicable to patient populations, do not necessarily apply to individual
      patients. In theory, radiobiological modeling, coupled with reliable predictive
      assays, can be used to rationalize the selection of patients for particular
      schedules in trials. MATERIALS AND METHODS: Linear-quadratic modeling of
      radiotherapy can be used to simulate a clinical trial. This is achieved by random
      sampling techniques where the key radiobiological parameters (alpha, beta, T(pot)
      and clonogen number) are selected from known or expected ranges. Clinical trial
      design in radiotherapy may be improved by formal radiobiological assessment
      designed to estimate the likely changes in tumor cure probability (TCP) and the
      likely normal tissue biologically effective dose (BED). Modeling may also be used
      to rationalize the allocation of patients to a test or standard schedule or for
      individual optimization of a treatment schedule. Such approaches depend on there
      being reliable predictive assays of the radiobiological parameters in individual
      patients. The influence of variations in predictive assay accuracy on the
      improved outcomes are assessed. RESULTS: Clinical trials, which have been
      preceded by modeling simulation, offer potentially substantial improvements in
      the results of cancer treatment by radiotherapy. These exceed the usual gains
      found in standard clinical trials. CONCLUSION: Future preclinical trial design
      should include modeling assessments that indicate how best to structure the
      trial.

PMID- 10924998
TI  - Commissioning an image-guided localization system for radiotherapy.
AB  - PURPOSE: To describe the design and commissioning of a system for the treatment
      of classes of tumors that require highly accurate target localization during a
      course of fractionated external-beam therapy. This system uses image-guided
      localization techniques in the linac vault to position patients being treated for
      cranial tumors using stereotactic radiotherapy, conformal radiotherapy, and
      intensity-modulated radiation therapy techniques. Design constraints included
      flexibility in the use of treatment-planning software, accuracy and precision of
      repeat localization, limits on the time and human resources needed to use the
      system, and ease of use. METHODS AND MATERIALS: A commercially marketed,
      stereotactic radiotherapy system, based on a system designed at the University of
      Florida, Gainesville, was adapted for use at the University of Washington Medical
      Center. A stereo pair of cameras in the linac vault were used to detect the
      position and orientation of an array of fiducial markers that are attached to a
      patient's biteblock. The system was modified to allow the use of either a
      treatment-planning system designed for stereotactic treatments, or a general,
      three-dimensional radiation therapy planning program. Measurements of the
      precision and accuracy of the target localization, dose delivery, and patient
      positioning were made using a number of different jigs and devices. Procedures
      were developed for the safe and accurate clinical use of the system. RESULTS: The
      accuracy of the target localization is comparable to that of other treatment
      planning systems. Gantry sag, which cannot be improved, was measured to be 1.7
      mm, which had the effect of broadening the dose distribution, as confirmed by a
      comparison of measurement and calculation. The accuracy of positioning a target
      point in the radiation field was 1.0 +/- 0.2 mm. The calibration procedure using
      the room-based lasers had an accuracy of 0.76 mm, and using a floor-based
      radiosurgery system it was 0.73 mm. Target localization error in a phantom was
      0.64 +/- 0.77 mm. Errors in positioning due to couch rotation error were reduced
      using the system. CONCLUSION: The system described has proven to have acceptable
      accuracy and precision for the clinical goals for which it was designed. It is
      robust in detecting errors, and it requires only a nominal increase in setup time
      and effort. Future work will focus on evaluating its suitability for use in the
      treatment of head-and-neck cancers not contained within the cranial vault.

PMID- 10924999
TI  - The role of proton therapy in the treatment of large irradiation volumes: a
      comparative planning study of pancreatic and biliary tumors.
AB  - PURPOSE: The purpose of this study was to examine the potential benefit of proton
      therapy for abdominal tumors. Extensive comparative planning was conducted
      investigating the most up-to-date photon and proton irradiation technologies.
      METHODS AND MATERIALS: A number of rival plans were generated for four patients:
      two inoperable pancreatic tumors, one inoperable and one postoperative biliary
      duct tumor. The dose prescription goal for these large targets was 50 Gy,
      followed by a boost dose up to 20 Gy to a smaller planning target volume (PTV).
      Photon plans were developed using "forward" planning of coplanar and noncoplanar
      conformal fields and "inverse" planning of intensity-modulated (IM) fields.
      Proton planning was simulated as administered using the so called spot-scanning
      technique. Plans were evaluated on the basis of normal tissues' dose-volume
      constraints (Emami B, Lyman J, Brown A, et al. Tolerance of normal tissue to
      therapeutic irradiation. Int J Radiat Oncol Biol Phys 1990;21:109-122) and
      coverage of treatment volumes with prescribed doses. RESULTS: For all cases, none
      of the forward calculated photon plans was able to deliver 50 Gy to large PTVs at
      the same time respecting the dose-volume constraints on all critical organs. Nine
      evenly spaced IM fields achieved or nearly achieved all maximum dose constraints
      to critical structures for two out of three inoperable patients. IM plans also
      obtained good results for the postoperative patient, even though the dose to the
      liver was very close to the maximum allowed. In all cases, photon irradiation of
      large PTV1s to 50 Gy followed by a 20 Gy boost entailed a risk very close to or
      higher than 5% for serious complications to the kidneys, liver, or bowel. Simple
      arrangements of 2, 3, and 4 proton fields obtained better dose conformation to
      the target, allowing the delivery of planned doses including the boost to all
      patients, without excessive risk of morbidity. Dose homogeneity inside the
      targets was also superior with protons. CONCLUSION: For the irradiation of large
      PTVs located in the abdominal cavity, where multiple, parallel structured organs
      surround the target volumes, proton therapy, delivered with a sophisticated
      isocentric technique, has the potential to achieve superior dose distributions
      compared with state-of-the-art photon irradiation techniques. IM photon plans
      obtain better results in the postoperative case, because the reduced volume
      lessens the effect of the unavoidable increase of integral dose to surrounding
      tissues.

PMID- 10925000
TI  - An off-line strategy for constructing a patient-specific planning target volume
      in adaptive treatment process for prostate cancer.
AB  - PURPOSE: To improve the efficacy of dose delivery and dose escalation for
      external beam radiotherapy of prostate cancer, an off-line strategy for
      constructing a patient-specific planning target volume is developed in the
      adaptive radiotherapy process using image feedback of target location and patient
      setup position. MATERIALS AND METHODS: We hypothesize that a patient-specific
      confidence-limited planning target volume (cl-PTV), constructed using an initial
      sequence of daily measurements of internal target motion and patient setup error,
      exists and ensures that the clinical target volume (CTV) in the prostate cancer
      patient receives the prescribed dose within a predefined dose tolerance. A
      patient-specific bounding volume to correct for target location and compensate
      for target random motion was first constructed using the convex hull of the first
      k days of CT measurements. The bounding volume and the initial days of CT
      measurements were minimized based on a predefined dosimetric criterion. The
      hypothesis was tested using multiple daily CT images by mimicking the actual
      treatment of both conventional 4-field-box and intensity-modulated radiotherapy
      (IMRT) on each of 30 patients with prostate cancer. For each patient, a patient
      specific setup margin was also applied to the bounding volume to form the final
      cl-PTV. This margin was determined using the random setup error predicted from
      the initial days of portal imaging measurements and the residuals after
      correcting for the systematic setup error. RESULTS: The bounding volume
      constructed using daily CT measurements in the first week of treatment are
      adequate for the conventional beam delivery to achieve maximum dose reduction in
      the CTV of 2% or less of the prescription dose, for at least 80% of patients (p =
      0.08), and 4.5% or less for 95% of patients (p = 0.1). However, for IMRT
      delivery, 2 weeks of daily CT measurements are required to achieve a similar
      level of the dosimetric criterion, otherwise the maximum dose reduction of 7%, on
      average, in the CTV is expected. Furthermore, the patient-specific setup margin
      required for the IMRT treatment is at least twice larger than that for the
      conventional treatment, to maintain the same dosimetric criterion. As compared to
      the conventional PTV, the volume of cl-PTV is significantly reduced, while
      maintaining the same dosimetric criterion. CONCLUSION: The cl-PTV for prostate
      treatment can be constructed within the first week of treatment using the
      feedback of imaging measurements. The cl-PTV has the capability to exclude the
      systematic variation and compensate for the patient-specific random variation on
      target location and patient setup position. This implies that in the current off
      line image feedback adaptive treatment process, a single plan modification can be
      performed within the second week of treatment to improve the efficacy of dose
      delivery and dose escalation for external beam therapy of prostate cancer.

PMID- 10925002
TI  - Two new diterpenoids from Salvia triloba.
AB  - Two new diterpenoids, trilobic acid (1) and trilobiol (2), have been isolated
      from the methanolic extract of Salvia triloba. Their structures were elucidated
      with the aid of NMR spectroscopy including two-dimensional-NMR techniques.

PMID- 10925003
TI  - Caffeic and coumaric acid esters from Calystegia soldanella.
AB  - Esters of trans-4-hydroxycinnamic acid, cis-4-hydroxycinnamic acid and trans-3,4
      dihydroxycinnamic acid with long-chain alcohols (n=15-20), were isolated from the
      stems of Calystegia soldanella.

PMID- 10925004
TI  - Diterpenoids from Isodon lophanthoides.
AB  - A new diterpenoid was isolated from the leaves of Isodon lophanthoides, together
      with two known diterpenoids, lophanic acid and 8(17),12,14-labdatriene-19-oic
      acid. The structure of the new compound was determined to be 11 beta
      hydroxyisopimara-8,15-diene-3-one (1) on the basis of spectroscopic evidence.

PMID- 10925005
TI  - Isoflavonoid production by callus cultures of Maackia amurensis.
AB  - Callus cultures were established from the different parts of Maackia amurensis
      plants and analyzed for isoflavonoids. The isoflavones daidzein, retuzin,
      genistein and formononetin and the pterocarpans maakiain and medicarpin were
      found to be produced by these cultures. The content of isoflavones and
      pterocarpans was essentially the same in cultures derived from leaf petioles,
      inflorescences and apical meristems of the plant. The maximal yield of
      isoflavones and pterocarpans in calluses was 20.8 mg/g cell dry wt.,
      approximately four times higher than the content of the heartwood of M. amurensis
      plants. Unlike wild-growing plants, none of the cell cultures had the ability to
      accumulate stilbenes.

PMID- 10925006
TI  - Sesquiterpene lactones from Pulicaria crispa.
AB  - The investigation of Pulicaria crispa gave a new guaianolide identified as 1
      beta,4 beta-dihydroxy-5 alpha (H)-guaia-10(14),11(13)-dien-8 alpha,12-olide (5).

PMID- 10925007
TI  - Flavonolignan production from Silybum marianum transformed and untransformed root
      cultures.
AB  - Explants from seeds of Silybum marianum were used to produce either transformed
      ('hairy') or untransformed root cultures. Silybin, isosilybin, silychristin and
      silydianin were found in untransformed root cultures, by means of TLC and HPLC.
      In contrast, only isosilybin and traces of silychristin and silydianin were
      identified in the 'hairy' root cultures.

PMID- 10925008
TI  - Preliminary toxicity study on the individual and combined effects of Citrullus
      colocynthis and Nerium oleander in rats.
AB  - The toxicity of diet containing 10% of Citrullus colocynthis fruits or 10% of
      Nerium oleander leaves or their 1:1 mixture (5%+5%) for rats treated for 6 weeks
      was determined. Dullness, ruffled hair, decreased body weight gains and feed
      efficiency, and enterohepatonephropathy characterised treatment with C.
      colocynthis and N. oleander given alone. Diarrhoea was a prominent sign of C.
      colocynthis poisoning. Organ lesions were accompanied by leucopenia, anaemia and
      alterations in serum AST, ALT and ALP activities and concentrations of total
      protein, albumin, urea, bilirubin and other serum constituents. Feeding the
      mixture of C. colocynthis and N. oleander caused more marked effects and death of
      rats.

PMID- 10925009
TI  - A new prenylated flavanone glycoside from the seeds of Glircidia maculata.
AB  - A new flavanone glycoside, 5,4'-dihydroxy-6-prenylflavanone 4'-O-beta-D
      xylopyranosyl-(1-->2)-alpha-L-rhamnopyranoside (1), was isolated from the seeds
      of Glircidia maculata.

PMID- 10925010
TI  - In vitro studies on the selective cytotoxic effect of crocetin and quercetin.
AB  - Crocetin (5-20 microg/ml), quercetin (10-40 microg/ml), and cisplatin (60-180
      microg/ml) used as a positive control drug, were tested against human
      rhabdomyosarcoma (RD) cells and African green monkey kidney (Vero) cells. The
      cell viability, morphological changes, and lactate dehydrogenase activity were
      assessed. RD cell growth was found to be inhibited dose dependently by the three
      tested compounds. Morphological observation by phase contrast microscopy revealed
      that both crocetin and quercetin caused intense damage only on the malignant (RD)
      cells, whereas mild toxic effect was seen with cisplatin also on normal (Vero)
      cells.

PMID- 10925011
TI  - A new isoflavanone from the stem bark of Erythrina latissima.
AB  - Two isoflavonoids--including the new compound 5,7-dihydroxy-2',4',5'
      trimethoxyisoflavanone (1)--six flavanones and a feruloyl ester were isolated
      from the stem bark of Erythrina latissima.

PMID- 10925012
TI  - Medicinal plants used for peptic ulcer in the Bangangte region, western Cameroon.
AB  - Thirty-nine plant species, traditionally used to treat peptic ulcers in the
      Bangangte region, Western Cameroon, are reported.

PMID- 10925013
TI  - A new flavonoid from the aerial parts of Chrysanthemum viscidehirtum.
AB  - From the aerial parts of Chrysanthemum viscidehirtum, a new flavonoid, 2"
      glucosyl-8-C-glucosyl-4'-O-methylapigenin (1) was isolated.

PMID- 10925014
TI  - A new ent-kaurane diterpenoid from Isodon phyllostachys.
AB  - A new ent-kaurane diterpenoid, phyllostachysin C (1), together with five known
      compounds, sculponeatins B and C, nodosin, ursolic acid and 2 alpha
      hydroxyursolic acid, were isolated from the leaves of Isodon phyllostachys. The
      structure of 1 was elucidated on the basis of its spectral properties.

PMID- 10925015
TI  - A new secoiridoid glycoside from Lonicera angustifolia.
AB  - A new secoiridoid glycoside, 6'-O-beta-apiofuranosylsweroside (1), together with
      the known compounds sweroside, loganin, beta-sitosterol, oleanolic acid, ursolic
      acid and methyl-4-hydroxy benzoate have been identified from the leaves of
      Lonicera angustifolia. The structure of the new compound has been elucidated on
      the basis of spectroscopic and chemical evidence.

PMID- 10925016
TI  - An antioxidant sinapic acid ester isolated from Iberis amara.
AB  - The isolation of 6-O-sinapoyl sucrose (1) from Iberis amara seeds and an
      evaluation of its antioxidative properties in comparison with sinapic acid and
      ascorbic acid are reported.

PMID- 10925017
TI  - Antibacterial activity of some medicinal plants from San Juan, Argentina.
AB  - The antibacterial activities and preliminary phytochemical screening of 13 plants
      used as folk medicine in San Juan, Argentina, are reported.

PMID- 10925018
TI  - Antimicrobial activity of Pterocarpus osun stems.
AB  - Phytochemical and antimicrobial screening of extractives from Pterocarpus osun
      elder stems showed significant activities due to different classes of new
      isolated constituents.

PMID- 10925019
TI  - Antibacterial activity of Alchornea cordifolia stem bark.
AB  - The results of a preliminary antimicrobial screening of the petroleum ether,
      acetone, ethanol and methanol successive extracts of Alchornea cordifolia stem
      bark are reported.

PMID- 10925020
TI  - Antibacterial activity of Litsea glutinosa bark.
AB  - The methanol extract of the bark of Litsea glutinosa showed antibacterial
      activity, comparable to chloramphenicol, against all 16 tested microorganisms.

PMID- 10925021
TI  - Antibacterial activity of Piliostigma thonningii stem bark.
AB  - Piliostigma thonningii stem bark 60% methanolic extract exhibited activity
      against six out of eight bacterial isolates at a concentration of 20 mg/ml.

PMID- 10925022
TI  - Hypoglycaemic activity of Ocimum gratissimum in rats.
AB  - The hypoglycaemic effect of the methanolic extract of Ocimum gratissimum leaves
      was evaluated in normal and alloxan-induced diabetic rats. Intraperitoneal
      injection of the extract (400 mg/kg) significantly reduced plasma levels both in
      normal and diabetic rats by 56 and 68%, respectively.

PMID- 10925023
TI  - Antibacterial activity of Alangium salviifolium flowers.
AB  - The methanol extract of Alangium salviifolium flowers showed a wide spectrum of
      antibacterial activity against both gram-positive and gram-negative bacteria.

PMID- 10925024
TI  - Antibacterial activity of linoleic and oleic acids isolated from Helichrysum
      pedunculatum: a plant used during circumcision rites.
AB  - The antibacterial activity-guided fractionation of the dichloromethane extract of
      leaves of Helichrysum pedunculatum resulted in the isolation of linoleic and
      oleic acids. Linoleic acid inhibited the growth of all the Gram-positive
      bacterial species tested with the minimum inhibitory concentration (MIC) varying
      between 0.01 and 1.0 mg/ml. Oleic acid was active against three of the five Gram
      positive bacteria at a MIC of 1.0 mg/ml. Both compounds were inactive against the
      Gram-negative species tested. A synergistic effect between the two fatty acids
      was observed against Staphylococcus aureus and Micrococcus kristinae.

PMID- 10925025
TI  - Antimicrobial activity of the essential oil of Lantana camara.
AB  - The essential oil of Lantana camara, tested against seven bacteria and eight
      fungi, showed a wide spectrum of antibacterial and antifungal activities.

PMID- 10925026
TI  - Phytoecdysteroids from Atriplex nummularia.
AB  - A bioassay for ecdysteroid agonists/antagonists and ecdysteroid-specific
      radioimmunoassays, together with a photo-diode-array detector-monitored high
      performance liquid chromatography, have been used to analyse a methanol extract
      of the seeds of Atriplex nummularia. This yielded two phytoecdysteroids, 20
      hydroxyecdysone (1) and polypodine B (2).

PMID- 10925027
TI  - Quercetin 3-O-(6"-caffeoyl)-beta-D-galactopyranoside from Polygonum viscosum.
AB  - The methanol extract of the whole plant parts of Polygonum viscosum has yielded a
      flavonol glycoside, 3-O-(6"-caffeoyl)-beta-D-galactopyranoside (1), the structure
      of which has been determined unambiguously by UV and a series of one- and two
      dimensional NMR experiments, notably, (1)H, (13)C, DEPT, COSY45, HMBC and HMQC.

PMID- 10925028
TI  - Julocrotine, a glutarimide alkaloid from Croton membranaceus.
AB  - The isolation and spectral data of julocrotin (1), a glutarimide alkaloid from
      Croton membranaceus are reported.

PMID- 10925029
TI  - Quercetin 3-arabinopyranoside, a major flavonoid compound from Alchemilla
      xanthochlora.
AB  - Quercetin 3-O-alpha-L-arabinopyranoside (1) was isolated from the aerial parts of
      Alchemilla xanthochlora and characterized by spectroscopic analysis.

PMID- 10925030
TI  - Second Workshop of Italian Society of Phytochemistry (SIF) on 'Polyphenols in
      Food'. March 20--21, 2000-Florence (Italy).

PMID- 10925031
TI  - Gating or switching? Gating is a better model of prospective timing (a response
      to 'switching or gating?' by Lejeune).
AB  - Lejeune (1998) (Switching or gating? The attentional challenge in cognitive
      models of psychological time. Behav. Process. 44, 127-45) analyzed and compared
      two models of prospective timing: the classical switching model and the
      attentional-gate model. Lejeune argued that a modified switch notion, which can
      be opened and closed in a frequency which reflects the amount of attentional
      resources allocated for timing can provide a satisfactory explanation for the
      impact of attention on prospective timing, and therefore the notion of an
      'attentional switch' is favored over adding an 'attentional gate.' In the present
      analysis, the two competing models are compared in terms of correspondence with
      the nature of attentional processes, as well as in terms of logical analysis and
      explanatory power. Based on this comparison, it is argued that gating is a better
      model of prospective timing than switching.

PMID- 10925032
TI  - Risk-sensitive foraging in rats: the effects of response-effort and reward-amount
      manipulations on choice behavior.
AB  - The literature on risk-sensitive foraging theory provides several accounts of
      species that fluctuate between risk-averse and risk-prone strategies. The daily
      energy budget rule suggests that shifts in foraging strategy are precipitated by
      changes in the forager's energy budget. Researchers have attempted to alter the
      organism's energy budget using a variety of techniques such as food deprivation,
      manipulation of ambient temperatures, and delays to food reward; however,
      response-effort manipulations have been relatively neglected. A choice
      preparation using a wheel-running response and rats examined risk-sensitive
      preferences when both response effort and reward amounts were manipulated.
      Concurrently available reinforcement schedules (FI/60 and VI/60) yielded
      equivalent food amounts per unit time in all treatments. Two levels of response
      effort (20 or 120 g tangential resistance) and two levels of reward amount (three
      or nine pellets) were combined to form four distinct response-effort/reward
      amount pairings. Increasing reward amounts significantly shifted choice toward
      the FI schedule in both response-effort conditions. The incidence of choice
      preference and the magnitude of shifts in choice were greater for the high
      response-effort conditions than for the low response-effort conditions.
      Implications of the significant interaction between response effort and reward
      amount are discussed in terms of a general energy-budget model.

PMID- 10925033
TI  - The role of environmental familiarization in novel-object preference.
AB  - The experiments in this report examined the behavioral variables modulating novel
      object preference in a widely used 'object recognition' preparation. This
      preparation takes advantage of the tendency of rats to interact more with a novel
      than a familiar 'sample' object in a free-choice situation. Experiment 1 examined
      the interaction between environmental familiarization and the duration of sample
      object exposure in the development of a novel-object preference. Interaction with
      the sample object during sample-object exposure was increased when rats were
      given time in the environment prior to presentation of the sample object. Also,
      provided that the sample-object exposure was greater than 2 min, rats given
      environmental familiarization time prior to sample-object exposure displayed a
      novel-object preference. Rats that received the same amount of sample-object
      exposure without prior exposure to the environment alone did not discriminate
      between the sample and novel object. In Experiments 2 and 3, sample-object
      exposure occurred in a different environment than the novel-object test. Novel
      object preference was not affected regardless of whether that testing environment
      was familiar or novel. This result differs from previous work that finds that an
      object recovers some novelty when moved to a new spatial location.

PMID- 10925034
TI  - Trophic egg laying in the spider, Amaurobius ferox: mother-offspring interactions
      and functional value.
AB  - Offspring of the spider Amaurobius ferox (Araneae, Amaurobiidae) were provided
      with trophic eggs of their mother the day after their emergence from the egg sac.
      This precisely timed egg laying followed after a series of mother-offspring
      interactions involving specific behaviors. Experiments showed that the trophic
      egg laying of the mother (providing she is in the appropriate reproductive
      condition) necessitated not only their presence, but also the stimulating
      behavior of the spiderlings. By stimulating their mother the spiderlings actually
      inhibited the normal maturation of the second generation of maternal eggs and
      prompted the release. Comparing to the trophic egg-deprived clutches, the
      clutches provided with the trophic eggs developed with higher body mass, earlier
      moulting and matriphagy. More offspring survived at the matriphagy with the
      mother normally provisioning the first clutch with trophic eggs rather than with
      the mother that did not produced the trophic eggs for her first clutch but for
      her second clutch. By turning her potential second generation into food, the
      mother increases her reproductive success.

PMID- 10925035
TI  - Training history affects magnitude of spontaneous recovery from extinction of
      appetitive conditioned responding.
AB  - Three experiments examined spontaneous recovery from extinction of appetitive
      conditioned responding (CR) as a function of training history. Rats first
      received reinforced and non-reinforced conditioning trials. Groups of rats were
      equated for total number of reinforced trials but differed in the number of non
      reinforced trials, or in the order of reinforced and non-reinforced trials. CR
      was then extinguished in all groups. Subsequently, the extent of recovery of CR
      was assessed in a test session performed either 1 or 17 days after the last
      extinction session. After a 17-day delay, rats that had received all reinforced
      trials immediately prior to the first extinction session showed stronger recovery
      than did rats having received all reinforced trials at the beginning of training,
      or interspersed among non-reinforced trials. No significant spontaneous recovery
      was observed after a 1-day test delay. These results, which may be of clinical
      relevance with respect to relapse after therapy, are explained in terms of the
      training schedules generating differences in strength of inhibitory associations,
      and a relatively long, but not a short, test delay attenuating these
      associations.

PMID- 10925036
TI  - Airborne transmission of bovine herpesvirus 1 infections in calves under field
      conditions.
AB  - A small scale transmission experiment was performed with bovine herpesvirus 1
      (BHV1) in a cattle population under field conditions. 10 calves were housed under
      strict hygienic conditions, with a distance of 4m between each calf. Five calves
      were experimentally infected with BHV1, two calves with strain Harberink and
      three with strain Lam, respectively. Experimentally infected calves were placed
      at 4 m distance from five susceptible sentinel calves. Airborne transmission to
      sentinel calves was detected using virus isolation and BHV1 specific polymerase
      chain reactions in samples of nasal fluids, and BHV1 specific antibodies in serum
      samples. Strain Harberink was hardly transmitted to sentinel calves, whereas
      strain Lam was transmitted to all sentinels. Estimating the rate of transmission
      per day, the total number of calves infected by one (strain Lam) infected calf
      was 1.18. Comparing this estimated transmission ratio between cattle at a
      distance of 4 m to the estimated transmission ratio R of BHV1 in susceptible
      commingled cattle reported before, the effect of the factor distance on the
      transmission ratio could be calculated. Extrapolating these results, a distance
      of 4.4 m between cattle populations would be necessary to reduce transmission for
      this strain to R<1.

PMID- 10925037
TI  - Rapid detection of porcine reproductive and respiratory syndrome viral nucleic
      acid in blood using a fluorimeter based PCR method.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus
      recognised world wide as an important cause of reproductive failure and pneumonia
      in pigs. American and European strains of PRRSV, differentiated antigenically and
      genomically, have been reported. PRRSV infections are currently diagnosed using
      serology, virus isolation and/or immunocytochemistry. In order to overcome
      various drawbacks associated with these techniques, conventional, block-based RT
      PCR methods for the detection of PRRSV nucleic acid in clinical samples have been
      described. These methods require gel electrophoresis for analysis of PCR products
      and present high risk of DNA carry-over contamination between the samples tested.
      We describe the detection of PRRSV RNA in serum samples and in blood impregnated
      filter disks (FDs), obtained from experimentally inoculated pigs, using a closed
      tube, fluorimeter-based PCR assay. The assay eliminates the use of gel
      electrophoresis, and is as sensitive and specific as the conventional block-based
      PCR assay, detecting positive samples as early as 1 day post-inoculation. We also
      report a rapid fluorimeter based PCR method for differentiating American and
      European strains of PRRSV.

PMID- 10925038
TI  - Antimicrobial susceptibility of Mycoplasma hyorhinis.
AB  - A broth microdilution technique was used to determine the antimicrobial
      susceptibility of 15 field isolates of Mycoplasma hyorhinis to 10 antimicrobial
      agents, representative of different classes, and contrasting newer agents to
      existing ones. For the macrolides, the MIC(90) for tylosin and tilmicosin was 1
      and 4 microg/ml, respectively, but was > or = 16 microg/ml for erythromycin.
      Tetracycline, lincomycin and enrofloxacin each had an MIC(90) of 2 microg/ml. The
      mycoplasma had similar levels of susceptibility to the aminoglycoside and
      aminocyclictol classes exhibiting an MIC(90) of 4 microg/ml for gentamicin and 2
      microg/ml for spectinomycin. The isolates exhibited high MICs to
      trimethoprim/sulfamethoxazole with an MIC(90) > or = 16/304 microg/ml. In
      summary, M. hyorhinis isolates from the US had low MICs against a variety of
      antimicrobials tested, with the exception of erythromycin and
      trimethoprim/sulfamethoxazole.

PMID- 10925039
TI  - A nested PCR assay for the detection of Mycoplasma hyopneumoniae in
      tracheobronchiolar washings from pigs.
AB  - A nested polymerase chain reaction (PCR) was developed for the detection of
      Mycoplasma hyopneumoniae, the etiological agent of enzootic pneumonia, in
      tracheobronchiolar washings from live pigs. Two nested pairs of oligonucleotide
      primers were designed from the sequence of a specific DNA probe (I 141; accession
      number U02537). The primer combination was Hp1/Hp3 for the first step PCR while
      the nested primers (Hp4/Hp6) allowed amplification of a 706 bp fragment. All
      strains of M. hyopneumoniae tested in this study could be detected by the nested
      PCR. DNA from other bacterial species isolated from the respiratory tract of pigs
      or from other mycoplasmal species were not amplified. The detection limit was
      estimated to be 1 fg, corresponding approximately to one organism, while in the
      one step PCR previously described 4 x 10(2) organisms were required. The nested
      PCR was evaluated on 362 tracheobronchiolar lavages collected from pigs at 2, 4
      and 6 months of age in eight herds chronically infected with M. hyopneumoniae.
      The nested PCR was compared to a blocking ELISA performed with sera collected
      from the same pigs at the same ages, and to an immunofluorescence test at
      slaughter on 65 lungs from 6-month old pigs. The comparison indicated that the
      nested PCR was significantly (p<0.05) more sensitive (157 positive results of 362
      samples) than ELISA (118 positive results of 362 samples) for detection of M.
      hyopneumoniae infection. Nested PCR was also significantly more sensitive (54
      positive results of 65 samples) than immunofluorescence (29 positive results of
      65 samples) for detection of M. hyopneumoniae in pig lungs at slaughter.
      Moreover, the nested PCR was used to confirm the absence of the mollicute in a
      pig herd without any history of M. hyopneumoniae infection. Thus, nested PCR
      appears to be a useful test to assess M. hyopneumoniae infection on pig farms.

PMID- 10925040
TI  - Purification and characterization of the fimbria F18ac (2134P) isolated from
      enterotoxigenic Escherichia coli (ETEC).
AB  - The adhesin F18ac purified on Sepharose CL 4B column chromatography and SDS-PAGE
      stained with Coomassie Blue and Western blotting using specific anti-F18ac serum
      presented one band of approximately 17kDa. Gold immunolabeling revealed that the
      adhesin F18ac has a fimbrial structure on the bacterial surface. The first 27
      amino acid residues of the N-terminal portion of the adhesin F18ac, showed 92.5%
      homology (25 amino acids) with the F107 (F18ab) fimbriae.

PMID- 10925042
TI  - Strain discrimination of a novel serotype of Salmonella from harbour porpoises
      (Phocoena phocoena) by molecular techniques.
AB  - The relatedness of 41 isolates of Salmonella of a novel serotype (antigenic
      formula 4,12:a:-) of serogroup B, obtained from harbour porpoises (Phocoena
      phocoena) stranded at various sites around the coastline of Scotland, was
      assessed by two molecular typing methods. Ribotyping showed that these isolates
      belonged to seven EcoRI (E) ribotypes and 11 PstI (P) ribotypes that were, in
      each case, distinct but closely related. Combined ribotyping data identified 15
      different E/P ribotypes, the most common of which, E1/P1, was represented by 15
      isolates from 14 animals stranded on both east and west coastlines. Strain
      discrimination achieved by E/P ribotyping was high (D=0.84). IS200 profiling
      revealed only three different fingerprints and strain discrimination by this
      method alone was poor (D=0.39). When E/P ribotyping and IS200 profiling were used
      together, they revealed the existence of 17 different types among the 41 isolates
      which formed two distinct, but related, groups of Salmonella serotype 4,12:a:-.
      This information should prove helpful in future studies examining the mode of
      transmission of this novel salmonella serotype and its association with disease
      in harbour porpoises.

PMID- 10925041
TI  - Pathogenic characteristics of Escherichia coli strains isolated from newborn
      piglets with diarrhea in Brazil.
AB  - Ninety-one Escherichia coli isolates obtained from diarrheic and normal feces of
      newborn piglets (0-11 days of age) from three states of Brazil were assessed for
      phenotypic and genotypic characteristics associated with pathogenic processes.
      These isolates expressed fimbriae F18ac and type 1, but not fimbriae K88, K99,
      987P or F41. Genes for toxins (LT-I, STa, SLT-I, SLT-II, SLT-IIv) either
      individually or combined were found to be present in most of the diarrheic
      strains (65.7%) and in 42.8% of the non-diarrheic ones. The eaeA gene was present
      in 25.7% of the diarrheic isolates and in 9.5% of the non-diarrheic ones.
      Colicin, hemolysin and aerobactin were also found to be produced by some strains
      from both sources. Because of the great variety of biological characteristics
      associated with different illness processes, we suggest that, in Brazil, pigs may
      act as a reservoir for transmission of Escherichia coli strains to other animals.

PMID- 10925043
TI  - Pathogenicity of Rhodococcus equi expressing a virulence-associated 20 kDa
      protein (VapB) in foals.
AB  - Rhodococcus equi strains of intermediate virulence (IMV) for mice possess a 20kDa
      protein designated Virulence Associated Protein B (VapB) and a virulence plasmid
      of 79-100kb, and can be recovered from the submaxillary lymph nodes of pigs. The
      pathogenicity of such R. equi strains for foals is unknown. In this study, two
      foals, 42 and 43 days of age, were infected intratracheally with 10(6) and 10(9)
      cells of R. equi IMV strain A5, respectively. The foal infected with 10(9) cells
      of strain A5 became clinically ill, with the onset of illness (pyrexia and
      depression) occurring 21 days after inoculation. R. equi was isolated from the
      feces and tracheal washings of the foal from 14 to 28 days after inoculation. The
      foal infected with 10(6) cells of A5 showed no clinical signs, and no R. equi was
      isolated from any of the samples of feces or tracheal washings during the 28 days
      of observation. Two foals of 45 and 50 days of age were infected with 10(5) or
      10(6) of virulent R. equi ATCC 33701 having 15-17kDa surface proteins designated
      VapA. Both exhibited severe clinical signs (pyrexia, depression and anorexia) at
      12 and 13 days after inoculation. Histopathological examination revealed that
      strain A5 caused focal granulomatous pneumonia in the foals. R. equi IMV strain
      A5 was isolated from lung lesions of both foals and from the contents of the
      intestinal tracts of the foal infected with 10(9) bacteria. These results suggest
      that IMV R. equi having VapB is less virulent than virulent R. equi having VapA
      in foals. This finding supports our previous results on the pathogenicities of R.
      equi strains having these virulence-associated antigens assessed by mouse
      pathogenicity tests.

PMID- 10925046
TI  - Editorial.

PMID- 10925045
TI  - Production and evaluation of a panel of monoclonal antibodies against Haemophilus
      paragallinarum.
AB  - We report on the production and characterisation of monoclonal antibodies (MAbs)
      against Haemophilus paragallinarum, the causative agent of infectious coryza. A
      bank of 8 MAbs were produced by traditional techniques - four against the
      reference strain for Page serovar A (0083) and four against the reference strain
      for Page serovar C (Modesto). Seven of the eight MAbs were shown to be IgG(1)
      with one being nontypable. None of the MAbs had HI activity and none gave any
      detectable reaction when examined by Western blotting. None of the MAbs gave a
      positive reaction in the indirect ELISA with any of the eight type strains of
      Pasteurella species or sub-species. None of our 8 MAbs gave serovar specific
      reactions when used in an indirect ELISA format. There was a trend for the
      serovar A MAbs to give a higher titre with serovar A isolates/strains and a
      similar trend for the serovar C MAbs to give higher titres with the serovar C
      isolates/strains.

PMID- 10925044
TI  - Attenuation and immunogenicity of a Brucella abortus htrA cycL double mutant in
      cattle.
AB  - PHE1 is a htrA cycL double gene deletion mutant of virulent Brucella abortus
      strain 2308 (S2308) which has previously been evaluated in the murine and caprine
      models of bovine brucellosis. This report describes the results of studies
      conducted with this mutant in the natural bovine host. Six sexually mature, non
      gravid heifers were inoculated via the conjunctival sac with 1 x 10(10) colony
      forming units (CFU) of either the parental S2308 or the htrA cycL gene deletion
      mutant, PHE1. At 4, 7 and 11 days post-inoculation, PHE1 was found to colonize
      the bovine host at lower levels than S2308. In a second experiment, eight heifers
      in mid-gestation were infected with 1 x 10(7) CFU of either strain via the
      conjunctival sac. The virulent S2308 caused abortions or weak calves in 4/4 cows,
      while all four cows infected with PHE1 had healthy calves. Furthermore, PHE1
      exhibited decreased resistance to killing by cultured bovine neutrophils and
      macrophages compared to the parental strain. These studies demonstrate that the
      B. abortus htrA cycL gene deletion mutant PHE1 is highly attenuated in the bovine
      host when compared to the virulent parental S2308.

PMID- 10925047
TI  - Editorial: focus on quality assurance research development.

PMID- 10925049
TI  - Bacterial contamination of cellular blood products: the Canadian perspective.

PMID- 10925048
TI  - Cytokine accumulation in stored red cell concentrates: effect of buffy-coat
      removal and leucoreduction.
AB  - The accumulation of cytokines in stored red blood cell concentrates (RCCs) has
      been implicated as a potential cause of transfusion reactions associated with the
      use of such products. At present, it is unclear whether there is any link between
      residual leukocyte and/or platelet content with cytokine levels in various RCCs.
      In this study, we have therefore assessed cytokine levels of leukocyte (e.g.,
      IL8) and platelet (e.g., RANTES, TGF-beta1) origin in supernatants of RCCs
      prepared by the plasma reduced method or by depletion of the buffy coat. We have
      also assessed whether the Duffy antigen receptor (DARC, a promiscuous receptor
      for some chemokines) has any role in the diminution of cytokine levels in stored
      blood components by comparing cytokine levels in stored plasma reduced RCCs
      derived from both DARC +ve and DARC -ve individuals. In addition, comparison of
      filtered and non-filtered products of the same origin has also been conducted.
      Results showed that supernatants from DARC -ve concentrates contained higher
      levels of IL-8 up to days 14/15 of storage compared with DARC +ve RCCs. However,
      at later time points, similar levels of IL-8 were observed in RCCs regardless of
      their Duffy receptor status. For TGF-beta1 and RANTES, no significant difference
      in the levels of these cytokines was detected between DARC +ve and DARC -ve
      concentrates. Removal of leukocytes and platelets by conventional leukocyte
      filtration significantly reduced the accumulation of cytokines. Buffy coat
      reduced RCCs contained minimal amounts of IL-8 and TGF-beta1 but no RANTES. We
      conclude therefore, that the levels of cytokines in the supernatants of RCCs
      stored at 4 degrees C are related mainly to their leucocyte and platelet content.

PMID- 10925050
TI  - Detection of nucleic acid sequences from bacterial species with molecular genetic
      methods.
AB  - While blood products become more safe in terms of viral contamination, the risk
      of transfusion-related bacterial infection has re-emerged to one of the major
      hazards in transfusion medicine. In recent prospective studies the rate of
      contaminated platelets ranged from 0.04 to 0.5%, and a rate of transfusion
      reactions between 0.007% and 0.046%. It is generally agreed that most of the
      organisms isolated from donated blood originate from the normal skin flora or
      from the environment. As it is unlikely that antiseptic methods can achieve
      absolute sterilization of the skin before venepuncture, blood banks have to rely
      on laboratory tests to detect contaminated blood products before release. But
      most of the currently available methods detecting bacterial contaminations do not
      have the potential to be sensitive and fast enough for a routine contamination
      screening in transfusion services. Here we present two alternative strategies
      based on molecular genetic techniques (Real-Time-PCR and Haystack processing)
      that detect or semi-quantify bacterial rRNA gene sequences for the majority of
      bacterial species. In addition we discuss some aspects on target selection,
      routine preparation and residual 16S-rDNA-contamination of enzymes.

PMID- 10925051
TI  - White cell subsets in filtered red blood cell concentrates.

PMID- 10925052
TI  - New plasma-reduced synthetic media, Fukushima cocktails, for the storage of
      platelets for transfusion.
AB  - BACKGROUND: Donor plasma proteins are associated with non-hemolytic allergic
      reactions, such as urticaria or laryngeal edema, in platelet-transfusion
      recipients. Replacement of plasma with synthetic media from platelet concentrates
      (PCs) is considered to be effective in preventing such reactions. However,
      platelets preserved in media depleted of less than 10% plasma are reported to
      have functions inferior to those preserved in plasma. METHODS: Fukushima
      Cocktails (FCs) contain glycerol (25, 50 or 100mM), sodium acetate, glucose and
      other components. To test the effect and determine the most suitable
      concentration of glycerol for platelet preservation, functions of platelets
      including aggregation, hypotonic shock response and swirling pattern and released
      biochemicals were measured with platelets preserved in Fukushima Cocktails. The
      effects of residual plasma on platelet functions were also evaluated. Autologous
      platelets stored for 3 days in solution containing 50 mM glycerol were transfused
      into healthy volunteer donors to evaluate their safety and survival. RESULTS: The
      functions (aggregation and hypotonic shock response) of platelets preserved in
      Fukushima Cocktails with 10% residual plasma were preserved for 5-7 days as well
      as plasma controls, whereas platelets stored for 9 days in a medium lacking
      glycerol became swollen and beta-thromboglobulin and thromboxane B(2) increased.
      When the residual plasma was more than 5%, platelet functions including
      aggregation, hypotonic shock response and swirling pattern were well preserved
      for 7 days. The in vivo platelet survival rates at 24 and 48 h after transfusion
      of platelets stored for 3 days in Fukushima Cocktail were 77% and 60%,
      respectively, which were not less than autologous plasma-stored platelets.
      CONCLUSION: Glycerol at a concentration of around 50 mM has a beneficial effect
      on platelet preservation for more than 7 days. The results of these experiments
      indicate that platelets stored in Fukushima Cocktail should be useful clinically.

PMID- 10925053
TI  - IgM alloantibody detection by M-MPHA, a new solid-phase assay system.
AB  - New IgM alloantibody detection system that uses anti-human IgM-antibody
      sensitized magnetic particles mixed passive hemagglutination (IgM-M-MPHA) has
      been developed. IgM antibodies are well detected by direct agglutination using
      the saline tube test. Anti-IgM using IgM antibody detection is not used
      routinely. In our evaluation, IgM-M-MPHA showed good detection of IgM
      alloantibodies. When IgM-M-MPHA is used together with IgG-M-MPHA (anti-human IgG
      antibody-sensitized magnetic particles mixed passive hemagglutination),
      alloantibodies can be distinguished easily whether it is IgG, IgM or both.

PMID- 10925054
TI  - A pilot study of large volume apheresis of red blood cells and plasma during one
      donation by allogeneic blood donors.
AB  - As a pilot study, we assessed large volume apheresis of red blood cells (RBC) and
      plasma. The protocol was as follows: (a) 3-RBC group: 3 units (240 ml) of RBC
      were drawn, (b) RBC+P group: 2 units (160 ml) of RBC and 400 ml of plasma were
      drawn during one apheresis procedure, and (c) CONTROL GROUP: 400 ml of whole
      blood was drawn by a manual method. Each group contained 7 healthy male donors of
      body weight 54-65 kg. We were able to perform these apheresis procedures without
      serious complications. Recovery of RBC for the donors of the 3-RBC group was
      delayed, but the level returned to the pre-donation level within nine weeks. The
      decreased total protein and albumin in the RBC+P group recovered within one week.
      The apheresed RBCs demonstrated the same quality as the manually collected RBC.
      These findings suggest that this apheresis approach may be applicable for routine
      donation.

PMID- 10925055
TI  - Clinical and laboratory factors that affect the post-transfusion platelet
      increment.
AB  - Transfusion of platelet concentrates (PC) reduced the incidence of fatal
      hemorrhages in several thrombocytopenic conditions. Unfortunately, long-term
      platelet supportive care may be complicated by the development of a state of
      refractoriness, resulting in inadequate recovery of functional platelets. PC
      handling, clinical conditions of the patients and alloimmunization are the main
      factors affecting refractoriness. We evaluated the post-transfusion platelet
      increase in 25 patients (M=6, F=19) with hypomegakaryocytic thrombocytopenia
      receiving random ABO-compatible PC within 24 h after collection. Quality of PC
      was assessed by platelet count, pH measuring, LDH release, glycocalicin levels,
      CD-62 and CD-42b expression. Besides history, clinical status and therapy, we
      searched for the presence of anti-HLA class 1 and anti-HPA 1-4-5 antibodies. Only
      six patients (24%) were refractory to PC transfusion, as assessed by a corrected
      count increment (CCI)<5000. Four of such six patients (67%) had anti-HLA
      antibodies, as compared to zero of 19 responders (P<0.02). No other investigated
      clinical or laboratory feature was significantly different in refractory and
      responsive patients. Although post-transfusion bleeding time was shorter in
      responders than in refractory patients (297.33+/-249.95 versus 673.33+/-409.96;
      P<0.02), it did not significantly change even in patients with adequate correct
      count increment. Our data confirm the importance of anti-HLA antibodies in
      determining adequate post-transfusion recovery or refractoriness.

PMID- 10925056
TI  - Utility of red blood cell apheresis in autologous blood donation.
AB  - Although autologous blood donation is an alternative to allogeneic transfusion,
      some authors had questioned its cost-effectiveness. New techniques, like red
      blood cell apheresis could improve the cost-effectiveness of autologous blood
      transfusion, therefore we have valued the efficiency of this procedure in
      autologous blood donation. MATERIALS AND METHODS: We studied 131 patients
      undergoing different types of surgery who entered the preoperative autologous
      blood donation program over a one year period. Apheresis was performed with the
      MCS 3p from Haemeonetics. RESULTS: We were able to collect 304 red blood cell
      units from 131 patients. The average yield per procedure was two units (88 cases,
      67.2%). In 41 patients (31.3%), we collected 3 units and, in two cases, 4 units
      were collected. The mean volume of the units was 255 (191-280). 18 (13.7%
      patients had an adverse reaction. Most of these were mild. Only in one case was
      it necessary to stop the procedure. 202 units (66.4%) were transfused to 97
      patients (74%). 12 (9.2%) patients also used allogeneic transfusions (mean units:
      0.18+/-0.05 with a range 1-5). CONCLUSION: Red blood cell apheresis is a useful
      procedure in autologous blood donation.

PMID- 10925057
TI  - Assessment of perioperative blood transfusion in cardiac surgery using
      administrative data.
AB  - We have analysed the blood transfusion requirements in 288 consecutive adult
      patients undergoing cardiac surgery using data from the discharge reports, coded
      in accordance with the international disease classification. 114 patients were
      transfused (39.6%). The transfusion rate was higher in patients with a principal
      diagnosis of two valve disorders, acute/subacute ischemic heart disease,
      congenital anomalies, tumour and injuries. All of these had a transfusion rate
      greater than 50%. Controlling the confounding effects by multivariate logistic
      regression analysis, there was an adjusted association of the transfusion rate
      only with the principal diagnosis and with sex, not with type of admission,
      preoperative anemia, surgical procedure or age.

PMID- 10925058
TI  - Pre-separation storage of whole blood: the effect of temperature on red cell 2,3
      diphosphoglycerate and myeloperoxidase in plasma

PMID- 10925059
TI  - Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1
      diabetes. Incidence and predictors.
AB  - The pathogenesis of diabetic neuropathy is poorly understood. In this prospective
      study, we investigated the incidence rate and potential predictors for
      cardiovascular autonomic neuropathy (CAN) in a cohort of childhood-onset type 1
      diabetic patients. Subjects from the Epidemiology of Diabetes Complications Study
      were examined at baseline and then biennially. CAN was diagnosed by abnormal
      (</=1. 1) expiration/inspiration ratio during deep breathing. During the 4. 7
      year mean follow-up period, CAN developed in 104 patients from the 373 subjects
      who were free of CAN at baseline and provided follow-up data, an incidence
      density of 5.9 cases/100 person-years. Cox proportional hazard modeling showed
      age (relative risk [RR]=2.15, p=0.0001), HbA1 (RR=1.50, p=0.0002) and nephropathy
      (albumin excretion >200 ug/min) (RR=2.46, p=0.0001) to be significant independent
      predictors. Hypertension was, however, predictive if nephropathy was not included
      in the model. We conclude that beyond age and poor glycemic control, nephropathy
      is a significant risk factor for CAN and this association may explain some of the
      increased mortality seen in CAN.

PMID- 10925060
TI  - Assessing cardiovascular autonomic neuropathy in diabetes mellitus: how many
      tests to use?
AB  - The aim was to evaluate the relative importance of an established battery of five
      function tests used in the assessment of cardiovascular autonomic neuropathy
      (CAN) in diabetes employing spectral analysis of heart rate variability (HRV) as
      the reference test. In a population-based sample of 178 diabetic persons and 194
      non-diabetic controls, five function tests (E/I ratio, Valsalva, 30:15 ratio,
      Orthostatic-BP, and sustained Handgrip) and power spectral analysis of a 24-h
      Holter recording were carried out. The high-frequency power during nighttime
      (LnHF(NIGHT)) was taken to express the parasympathetic function and the daytime
      low-frequency power (LnLF(DAY)) to express the sympathetic function. The readings
      were log transformation when appropriate, age-corrected, and standardized to
      units of standard deviation. Combinations of the three mainly parasympathetic
      tests and the two mainly sympathetic tests were computed by averaging the
      standardized readings. A high value of the mean sum of squares in LnHF(NIGHT) or
      LnLF(DAY) - explained in regression analysis - was assumed to represent the
      better test or combination of tests. The three parasympathetic function tests
      each correlated significantly to LnHF(NIGHT). The E/I ratio had a correlation to
      LnHF(NIGHT) similar to the combination of the three parasympathetic tests and the
      combination of all five function tests, whereas Valsalva and 30:15 ratio had a
      significantly poorer association. Sustained Handgrip-correlated significantly
      poorer to LnLF(DAY) compared to Orthostatic BP and the combination of the two
      sympathetic tests explained a significantly smaller part of the variation in
      LnLF(DAY) and LnHF(NIGHT) than did the combination of all five tests. This study
      indicates that: (1) no information is gained by adding the sympathetic function
      tests to the parasympathetic tests, (2) the most informative test is the E/I
      ratio, (3) and knowledge about the degree of CAN as defined by reduced HRV is not
      significantly increased when the four other function tests assessed are added to
      the E/I ratio.

PMID- 10925061
TI  - Type IV collagen as an early marker for diabetic nephropathy in non-insulin
      dependent diabetes mellitus.
AB  - We measured urinary albumin (U-Alb) and type IV collagen (uIV.C) in spot urine
      collected from 82 patients with non-insulin-dependent diabetes mellitus (NIDDM)
      and 205 controls. Eighty-two NIDDM patients that had no increased excretion of
      either U-Alb or uIV.C were observed for 6 months. Prevalence of increased
      excretion of U-Alb and uIV.C at 6 months in these patients were 32.9%, and 62.2%,
      respectively. Increased excretion of uIV.C was detected in 27 patients without
      microalbuminuria. chi(2) analysis suggested that uIV.C was more sensitive than U
      Alb, and that hypertension enhanced increased excretion of both U-Alb and uIV.C.
      uIV.C was significantly correlated (P<0.01) with U-Alb but not glycosylated
      hemoglobin A1C (HbA1C) in NIDDM patients. Taken together, uIV.C may be a useful
      marker for early diabetic nephropathy.

PMID- 10925062
TI  - Quality of life associated with diabetes mellitus in an adult population.
AB  - To ascertain the quality of life associated with the health state of diabetes
      mellitus using utility value analysis. Consecutive adult patients with diabetes
      mellitus for at least 1 year and a mean age of 61.7 years (range 21-85 years)
      were interviewed in a cross-sectional fashion using standardized research
      methodology. Utility analysis values were obtained employing the time tradeoff
      method and were correlated with clinical parameters of the sample group, as well
      as with co-morbidities using the heteroscedastic Student's t-test and
      multivariate linear regression. The chi(2) distribution to test for independence
      was used to compare sample subgroups. With a sample of 292 patients, the mean,
      patient-preference-based, time tradeoff utility value associated with the health
      state of diabetes mellitus was 0.88 (standard deviation (SD)=0.17; 95% confidence
      interval (CI), 0.86-0.90). Repeat analysis confirmed the reproducibility of the
      data. Thus, the average diabetic was willing to trade away 12% of his or her
      remaining life in return for a diabetic-free health state. Factors associated
      with a significant decrease in diabetic-associated quality of life included: (1)
      the requirement for insulin (p=0.05), (2) the presence of depression (p=0.01),
      (3) the presence of diabetic retinopathy (p=0.03) and the presence of co
      morbidities in general (p=0.01). The health state of diabetes mellitus has a
      significant effect upon patient, preference-based quality of life. The presence
      of diabetic co-morbidities and dependence upon insulin appear to decrease quality
      of life. The utility value associated with the health state of diabetes mellitus
      is of substantial importance for use in the calculation of cost-effective
      analyses.

PMID- 10925063
TI  - The quality of life of elderly diabetic patients.
AB  - The objective of this study was to evaluate the health-related quality of life
      (HRQoL) of elderly diabetic patients. A cross-sectional, questionnaire survey of
      diabetic subjects aged 65-84 years (n=177 respondents) from three community
      health centers in Stockholm County. The HRQoL was assessed by the Swedish Health
      Related Quality of Life Survey (SWED-QUAL), a generic HRQoL questionnaire adapted
      from the Medical Outcomes Study (MOS) and consisting of 67 items covering broad
      aspects of the HRQoL. Diabetic subjects were compared with age- and gender
      matched controls from a random standard population sample (SPS) of the Swedish
      population. Medical data on the diabetic subjects were extracted from medical
      records. The HRQoL, as regarded 7 of the 13 scales, was poorer in diabetic
      subjects than in the SPS controls. These scales were "general health
      perceptions," "physical functioning," "satisfaction with physical health," "role
      limitations due to physical health," "pain," "sleep problems," and "role
      limitations due to emotional health." Atheromatous complications and nonvascular
      disease were significant predictors of a poor HRQoL. "Cognitive functioning" was
      the only HRQoL scale on which diabetic subjects with high levels of HbA(1c)
      (HbA(1c)>7.0%) scored worse than those with acceptable levels (HbA(1c)<7.0%). In
      our study, elderly diabetic subjects had a poorer HRQoL than the general
      population, especially regarding physical health. Poor metabolic control was
      associated with reduced cognitive function.

PMID- 10925064
TI  - Responsiveness of the SF-36 among veterans with diabetes mellitus.
AB  - To examine the responsiveness of the Medical Outcomes Study 36-Item Short Form
      (SF-36) to the development of diabetes complications over time. We studied a
      cohort of 331 diabetic veterans participating in a prospective study of risk
      factors for foot complications. Eight SF-36 scales [general health (GH), physical
      functioning (PF), social functioning (SF), mental health (MH), physical role
      (RP), emotional role (RE), bodily pain (BP), and vitality (VT)] and 25 diabetes
      complications characteristics (DCC) from history and symptom questionnaires and
      physical exam findings were compared over a mean interval of 3.1 years. The
      subjects were mostly married, white males with a mean age of 63.5 years, with
      primarily type 2 diabetes (91%) and a mean diabetes duration of 9.7 years at
      baseline. There was a statistically significant interval decrease in the GH scale
      of 6.1 points (effect size [ES] 0.24), PF decreased 9.7 (ES 0.38), SF decreased
      5.8 (ES 0.19), PR decreased 14.7 (ES 0.38), BP decreased 4. 0 (ES0.14), VT
      decreased 4.5 (ES 0.16), total DCC increased by 1.8 (ES 0.53), and hemoglobin
      A(1c) declined 1.3% (ES 0.48). An increase of >1 DCC was associated with an
      average loss of 7.2 to 11.8 points on six SF-36 scales (GH, PF, SF, RP, BP, VT).
      The development of any renal complication was related to decrements in five SF-36
      scales (GH, PF, SF, RP, VT) while the appearance of any neuropathy complication
      was associated with a decline in four SF-36 scales (GH, PF, PR, VT). These
      results imply that six of the SF-36 scales are responsive to the development of
      diabetes complications over time among elderly veterans, supporting their use in
      longitudinal research. Renal and neuropathy complications have the greatest
      effects on the SF-36.

PMID- 10925065
TI  - Insulin resistance in diabetic microangiopathies.
AB  - To investigate whether insulin resistance is associated with diabetic
      microangiopathies in type 2 diabetes mellitus, insulin sensitivity was measured
      in 133 type 2 diabetic subjects with or without diabetic retinopathy and/or
      nephropathy. Insulin sensitivity was measured by steady-state plasma glucose
      method or euglycemic glucose clamp method. Regarding retinopathy, in the insulin
      resistant group, advanced retinopathy (preproliferative and proliferative
      retinopathy) was more frequently observed compared with the insulin-sensitive
      group (significance: p<0.02). Similarly, as for nephropathy, the occurrence of
      continuous proteinuria in the insulin-resistant group was significantly (p<0.01)
      more frequent compared with the insulin-sensitive group. Insulin sensitivity
      expressed as glucose utilization and glucose clearance was significantly (p<0.05)
      lower in diabetic subjects with retinopathy (without nephropathy) compared with
      subjects without the microangiopathies after adjustment for age, body mass index
      (BMI), fasting blood glucose (FBS), and diabetic duration. Similarly, insulin
      sensitivity in subjects with nephropathy (without retinopathy) was significantly
      (p<0.05) decreased compared with those without microangiopathies. Furthermore,
      insulin resistance was significantly (p<0.01) severe in the subjects with both
      retinopathy and nephropathy than in those without the two microangiopathies.
      Insulin resistance of type 2 diabetes is closely associated with the progression
      of microangiopathies, and causal relationship between insulin resistance and
      microangiopathies has remained to be solved.

PMID- 10925066
TI  - Increased tubuloglomerular feedback reactivity is associated with increased NO
      production in the streptozotocin-diabetic rat.
AB  - The characteristics of the tubuloglomerular feedback (TGF) mechanism were
      examined in streptozotocin-diabetic rats. This model is known to induce damage in
      the distal tubular system and thus Tamm-Horsfall protein (THP) secretion. Three
      groups of male Sprague-Dawley rats were studied: (A) diabetic rats with blood
      glucose levels (BG)<19 mmol/l, (B) with BG>/=19 mmol/l, and (C) control rats.
      After 50 days, the diabetic rats had higher arterial blood pressure and increased
      TGF reactivity (delta P(SF)) than control rats. The proximal tubular free-flow
      pressure (P(T)) and stop-flow pressure (P(SF)) were reduced, while the glomerular
      filtration was normal. This indicates that the diabetic animals of this study
      were severely vasoconstricted. Inhibition of renal nitric oxide synthase (NOS)
      resulted in a greater increase of TGF reactivity in diabetic rats than in control
      rats. Diabetic rats also showed increased excretion rates of albumin and THP. The
      excretion rate of THP was associated with P(SF) (r=-0.88, p<0.01). In conclusion,
      diabetes mellitus was associated with an increased blood pressure and an
      increased TGF reactivity, which indicates that the diabetic rats were
      vasoconstricted. NOS inhibition increased the reactivity of TGF to greater extent
      in diabetic animals than in controls, indicating that the renal vasoconstriction
      was compensated for by an increased NO production.

PMID- 10925069
TI  - Preliminary in vitro toxicological evaluation of a series of 2
      pyridylcarboxamidrazone candidate anti-tuberculosis compounds: II(1).
AB  - The in vitro toxicity of two amidrazones I [N(1)-(3-benzyloxy-4
      methoxybenzylidene)-pyridine-2-carboxamidrazone] and II [N(1)-(4-benzyloxy-3
      methoxybenzylidene)-pyridine-2-carboxamidrazone] and their precursors PI (3
      benzyloxy-4-methoxybenzaldehyde) and PII (4-benzyloxy-3-methoxybenzaldehyde) was
      determined using a rat liver metabolism system with human mononuclear leucocytes
      (MNL) as target cells. The minimum inhibitory concentration for I and II was
      determined to be between 4 and 8 ug/ml against Mycobacteria fortuitum. In direct
      contact with human MNL at three concentrations, only II and isoniazid (INH) were
      significantly more toxic compared with control at 100 and 200 uM. With rat
      microsomes, INH and PII at 50 uM showed significant toxicity. In the two
      compartment system without a metabolising system, INH and II were significantly
      more toxic compared with control and I. In the presence of the metabolising
      system, INH and PI were more toxic than control and INH was more toxic compared
      with I. II was not significantly more toxic than control. INH caused more cell
      death in the presence of the metabolising system compared with its absence. Less
      toxic compared with INH, compound I has shown promise for future development as
      an antituberculosis drug.

PMID- 10925070
TI  - Fumonisin toxicity in a transgenic mouse model lacking the mdr1a/1b P
      glycoprotein genes.
AB  - The toxicity of fumonisin B(1) (FB(1)) was investigated in male mdr1a/1b double
      knockout (MDRK) mice, lacking the drug-transporting P-glycoproteins. These
      transgenic animals are deficient in their blood:brain barrier and accumulate
      different drugs in brain and other tissues. The MDRK and their wild-type
      counterparts, FVB mice, were injected subcutaneously with 2.25 mg/kg per day of
      FB(1) for 5 days and sampled one day after the last treatment in a protocol that
      has resulted in marked hepatic and renal damage in other strains. FB(1) caused
      liver enlargement in both FVB and MDRK. Hematological parameters were not
      affected in either strain. Plasma levels of alanine aminotransferase and
      aspartate aminotransferase, measures of liver damage, were increased by FB(1) in
      both FVB and MDRK mice. Histopathological evaluation of liver corroborated this
      finding. Kidney lesions were induced by FB(1) in both types of mice.
      Concentrations of free sphingosine and sphinganine increased in liver and kidney
      of both strains after the FB(1) treatment, although the increase in liver
      sphingoid bases was half as much in MDRK as compared to FVB. The levels of
      sphinganine-containing complex sphingolipids were increased in kidney. The levels
      of sphingosine-containing complex sphingolipids in kidney were unaffected by
      FB(1) treatment but were significantly lower in control MDRK than in FVB mice.
      The levels of neurotransmitters and their metabolites were similarly affected in
      both strains by FB(1), suggesting no influence of disrupted blood:brain barrier
      on FB(1)-induced neurotoxicity. In both strains, the liver mRNA for tumor
      necrosis factor alpha was increased; however, the increase was statistically
      significant only in FVB. It was apparent that mice deficient in P-glycoprotein do
      not exhibit greater sensitivity to FB(1), the cellular or brain transport of
      FB(1) appears to be independent of this multidrug transporting system.

PMID- 10925067
TI  - Octreotide administration in diabetic rats: effects on renal function and
      morphology.
AB  - The effects of synthetic somatostatin analogue, octreotide, on fractional kidney
      weight (FKW), urinary protein excretion (UPE), creatinine clearance (Cl(cre)) and
      renal morphological changes were studied in alloxan-diabetic and non-diabetic
      rats comparatively. Diabetic rats were treated with twice daily s.c. injections
      of octreotide (2x2.5 microg) for 90 days. Untreated diabetic and non-diabetic
      animals were used as reference. The body weights and blood glucose levels of the
      animals were followed-up throughout the study period. After 90 days, FKW and
      renal morphology were evaluated. When compared to octreotide-treated diabetic
      group (O-D: 1.96+/-0. 23), normal control rats (NC: 1.24+/-0.05) showed a lower
      FKW (P<0. 05) and the FKW value of non-treated diabetic controls (DC: 2.74+/-0.
      17) were significantly higher (P<0.05). Cl(cre) values were calculated at 45th
      and 90th days. At the 45th day, Cl(cre) values (ml/min) of O-D group (0.75+/
      0.06) and NC group (0.56+/-0.09) were significantly lower than non-treated DC
      group (1.05+/-0.1) (P<0.05). However, at the 90th day no significant difference
      in Cl(cre) was observed. At the 45th day, UPE (mg/dl/day) was significantly
      higher in non-treated DC group (1000.45+/-392.38) when compared to NC group
      (236+/-36.59) (P<0.005) and UPE levels of O-D group were only slightly lower than
      that of non-treated diabetic group. At the 90th day, no significant beneficial
      effect of octreotide on UPE was observed. Octreotide did not prevent the
      histopathological changes related to diabetes. In conclusion, 5 microg/day
      octreotide administrations to diabetic rats for 90 days prevented renal weight
      increase but this treatment were insufficient to decrease the histopathological
      changes, UPE and increased Cl(cre).

PMID- 10925068
TI  - Suicidal insulin overdose in a type 1 diabetic patient: relation of serum insulin
      concentrations to the duration of hypoglycemia.
AB  - We present a case of a 31-year-old Type 1 diabetic woman who self-administered
      2400 units of insulin mixture (70% NPH human insulin and 30% Regular human
      insulin) as a suicidal attempt. The subsequent hypoglycemia was prolonged
      probably due to delayed absorption of the subcutaneous insulin, but it was not
      very difficult to control despite the administration of large amounts of insulin.
      Although the estimated serum insulin level was not well correlated with the
      severity of hypoglycemia, the hypoglycemia subsided when the serum insulin level
      returned to the physiological level. Therefore, the study of insulin
      pharmacokinetics after insulin overdose may be useful to know the necessary
      duration of exogenous glucose administration required to manage the medical
      emergency of severe insulin intoxication in future cases.

PMID- 10925071
TI  - Deltamethrin induces delayed apoptosis and altered expression of p53 and bax in
      rat brain.
AB  - Our previous work indicates that deltamethrin induces degeneration and apoptosis
      in rat brain at 24 and 48 h after treatment. To determine whether molecular
      characteristics of apoptosis is involved in neurodegeneration in rat brain after
      deltamethrin treatment, we investigated the effects of deltamethrin on the mRNA
      expression of p53 and bax and their correlation with deltamethrin-induced
      apoptotic cell death in rat brain. Hematoxylin-eosin and cresyl violet staining
      revealed numerous degenerative cells in cortex and hippocampus at 5 and 24 h
      after deltamethrin treatment. Apoptotic cells were detected in cortex and
      hippocampus of treated rats at 24 h by in situ end labeling, whereas no apoptotic
      cells were observed in the same brain regions at 5 h after treatment. By using in
      situ hybridization, it was demonstrated that the increase of p53 and bax mRNA
      levels appeared at 5 and also at 24 h after treatment. The alterations in mRNA
      expression of p53 and bax preceded the occurrence of delayed apoptotic cell death
      in the same brain regions after deltamethrin treatment. These results indicate
      that (1) deltamethrin induces delayed apoptotic cell death, which may play an
      important role in deltamethrin-elicited neurodegeneration; (2) deltamethrin leads
      to the persistent increase of p53 and bax mRNA levels, which may contribute to
      delayed apoptosis in rat brain following deltamethrin treatment.

PMID- 10925072
TI  - Cytogenetic toxicity of methotrexate in mouse bone marrow.
AB  - Methotrexate (MTX), a widely used anticancer drug, was tested for its cytogenetic
      toxicity in mouse bone marrow after a single intraperitoneal treatment with three
      different doses i.e. at the rate of 2, 10 and 20 mg/kg b.w. of mice. The end
      points selected were chromosomal aberrations and mitotic index study at 24-h post
      treatment and micronucleus (MN) test at 30-h post-treatment. The induction of
      statistically significant number of chromosomal aberrations, percentage of
      aberrant metaphases and highly significant number of MN per thousand
      polychromatic erythrocytes by all the doses of MTX indicated it as highly
      clastogenic. MTX was found more clastogenic in male mice than the females and the
      intermediate dose tested (10 mg/kg) was found more effective than the other
      doses. In mitotic index study, none of the doses of MTX inhibited cell
      proliferation during the first post-treated cell cycle. The results were compared
      with the earlier reports on the clastogenicity and cell proliferation inhibition
      of MTX only after multiple treatments. The possible mechanism of the cytogenetic
      effects of MTX has been discussed.

PMID- 10925073
TI  - Effect of fumonisin B(1) on rat hepatic P450 system.
AB  - The effects of the mycotoxin fumonisin B(1) (FB(1)) on the hepatic cytochrome
      P450 system were investigated in male rats dosed daily by oral gavage with 3 mg
      FB(1) per kg body weight for 9 consecutive days. FB(1) treatment resulted in a
      reduced weight gain. At the same time, CYP2E activity was increased, which is
      considered to mark the metabolic changes inherent to growth retardation in young
      rats. Treatment with FB(1) also resulted in a selective inhibition of CYP2C11 and
      to a lesser extent, CYP1A2 in liver microsomes obtained from treated animals,
      whereas it did not affect significantly the activity of CYP2A1/2A2, CYP2B1/2B2,
      CYP3A1/3A2 and CYP4A. The significant inhibition of CYP2C11 is considered to
      reflect a suppressed activity of protein kinase activity resulting from the
      inhibition of sphingolipid biosynthesis caused by FB(1).

PMID- 10925074
TI  - Pharmacological property of tributyltin in vivo and in vitro.
AB  - Tributyltin (TBT), an assumed endocrine-disrupting chemical, is widely known to
      show harmful effects in invertebrates including the dioecious snails. As for
      mammals, there are several reports concerning TBT toxicology, but few indications
      about general pharmacology of TBT. In the present study, we comprehensively
      examined the pharmacological effects of TBT both in vivo and in vitro. TBT (0.3
      or 1.0 mg/kg) attenuated the small intestinal propulsive activity measured by the
      charcoal method in vivo, and caused concentration-dependent relaxation of
      isolated guinea-pig ileum in vitro (1.0x10(-8)-3.0x10(-6) M). TBT induced
      concentration-dependent relaxation of guinea-pig trachea, which was not inhibited
      by pre-treatment with a beta-adrenoceptor antagonist. TBT caused a concentration
      dependent contraction of rat aortae, and also evoked endothelium-dependent
      relaxation in the presence of an alpha-adrenoceptor antagonist. The relaxation
      was inhibited by a muscarinic receptor antagonist. TBT reduced the electrically
      evoked, sympathetic contractile responses of rat vas deferens, which were
      slightly prevented by an alpha(2)-adrenoceptor antagonist. These results suggest
      that TBT possesses diverse pharmacological properties in mammalian organs.

PMID- 10925075
TI  - Integrative urology: a spectrum of complementary and alternative therapy.

PMID- 10925076
TI  - Incidental renal tumors.

PMID- 10925077
TI  - Laparoscopic and percutaneous radiofrequency ablation of the kidney: acute and
      chronic porcine study.
AB  - OBJECTIVES: The chronic effects of renal radiofrequency ablation are unknown.
      Herein, we investigate the anatomic and physiologic sequelae of laparoscopic and
      percutaneous renal radiofrequency ablation in acute and chronic porcine models.
      METHODS: Our study comprised two phases-an acute phase and a chronic phase. In
      the acute phase, bilateral laparoscopic renal radiofrequency ablation was
      performed in 6 animals (12 renal units), which were euthanized immediately after
      surgery. In the chronic study, bilateral percutaneous renal radiofrequency
      ablation was performed in 5 animals (10 renal units). One animal each was
      euthanized at postoperative day 3, 7, 14, 30, and 90. RESULTS: Ultrasound
      monitored laparoscopic (n = 12) and percutaneous (n = 10) radiofrequency
      ablations of the lower pole of the kidney were technically successful in each
      instance. No intraoperative complications occurred. In the survival experiments,
      the radiolesions showed gradual spontaneous resorption and ultimate renal
      autoamputation, while maintaining pelvocalyceal integrity as confirmed by ex vivo
      retrograde ureteropyelogram. Serum creatinine and hematocrit remained stable in
      all survival animals. Postoperative complication occurred in 1 chronic animal
      with nonobstructive small bowel dilation at autopsy. CONCLUSIONS: Laparoscopic
      and percutaneous renal radiofrequency ablation are technically feasible. The
      anatomic and physiologic sequelae of renal radiosurgery are favorable. Improved
      techniques of real-time monitoring of the evolving renal radiolesion are
      necessary.

PMID- 10925078
TI  - Assessment of health-related quality of life in renal transplant and hemodialysis
      patients using the SF-36 health survey.
AB  - OBJECTIVES: To determine whether the health-related quality of life (HQOL) for
      renal transplant patients improved using SF-36 survey scores and to examine which
      clinical measures after renal transplantation are connected to aspects of their
      HQOL. METHODS: A total of 117 renal transplant patients and 114 hemodialysis
      patients, including 49 awaiting transplantation and 65 not awaiting
      transplantation, were included in this study. The scale scores of the SF-36
      survey concerning HQOL were compared between the two groups of patients. The
      relationships of the clinical episode and complications with the scale scores
      were examined. RESULTS: The renal transplant patients had significantly higher
      scores in the physical functioning, bodily pain, general health, and social
      functioning scales than did the hemodialysis patients. The role-physical
      functioning, bodily pain, and social functioning scales of the transplant
      patients were significantly higher than those of the hemodialysis patients not
      awaiting transplantation. In contrast, the scores, except for that of general
      health, of the transplant patients were not significantly different from those of
      the hemodialysis patients awaiting transplantation. Multiple regression analysis
      demonstrated that the scale scores of physical functioning, general health, and
      vitality were significantly dependent on the serum level of creatinine in the
      renal transplant patients (P <0.05). The scores of physical functioning and
      general health of the patients with a creatinine level >2 mg/dL were
      significantly lower than those of the patients with 1 mg/dL < creatinine level
      </=1.5 mg/dL or a creatinine level </=1 mg/dL (P <0.05). An episode of
      hospitalization was not related to the scale scores, but an instance of rejection
      had an effect on the scores of social functioning and role-emotional functioning.
      CONCLUSIONS: The SF-36 health survey is a short but comprehensive scale for
      evaluating a patient's HQOL. The renal transplant patients' HQOL improved
      compared with that of the hemodialysis patients. The most important factor
      affecting HQOL was the serum creatinine level at the time of testing with the SF
      36 survey.

PMID- 10925079
TI  - Microbiologic aerobic studies on normal male urethra.
AB  - OBJECTIVES: To carefully collect samples from the external urethral orifice,
      navicular fossa, and penile urethra and perform a semiquantitative evaluation and
      identification of gram-positive and gram-negative bacteria present in the normal
      male urethra. METHODS: Thirty uncircumcised male patients 18 to 40 years old
      without any inflammatory and/or infectious urethral processes were enrolled in
      this study. Samples were collected from the external urethral orifice, navicular
      fossa, and penile urethra with sterile alginate swabs that were immediately
      transferred to tubes containing buffered phosphate solution. Inoculation was done
      by spreading 0.01 mL of the buffered solutions on sheep blood agar plates and
      MacConkey agar plates; the plates were then incubated at 36.5 degrees C for 24
      hours. After this period, the quantification and identification of each type of
      colony was performed. RESULTS: Among the 30 patients studied, 12 (40%) had
      bacteria isolated from the three segments, 10 (33.3%) had bacterial colonization
      in two segments, and 8 (26.7%) had colonization in only one segment (external
      urethral orifice). Staphylococcus coagulase-negative species, group viridans
      alpha-hemolytic streptococci, Corynebacterium species, and Enterococcus species
      were the bacteria more frequently isolated from these three segments.
      CONCLUSIONS: From the findings in this study, it was clear that the bacterial
      urethral flora was abundant, not evenly distributed, concentrated in the external
      urethral orifice and navicular fossa, and basically consisted of gram-positive
      aerobic bacteria.

PMID- 10925080
TI  - Renal cell carcinoma metastatic to the pancreas: a single-institution series and
      review of the literature.
AB  - OBJECTIVES: To present a series of 5 patients with solitary metastatic renal cell
      carcinoma (RCC) to the pancreas after radical nephrectomy at our institution and
      review the published reports of this rare event. METHODS: A retrospective review
      of the records of 5 patients with histologically confirmed RCC metastatic to the
      pancreas after radical nephrectomy was performed. A total of 5 patients (4 men, 1
      woman) with a median age of 56 years (range 54 to 68) underwent radical
      nephrectomy for primary RCC. The pathologic stage was Robson I (n = 3) or Robson
      III (n = 2), with a left-sided tumor occurring in 3 patients and a right-sided
      tumor in 2 patients. The median interval from nephrectomy to the diagnosis of the
      pancreatic metastasis was 12 years (range 4 to 15). All patients were symptomatic
      at presentation, including weight loss (n = 3), abdominal pain (n = 3), early
      satiety (n = 1), steatorrhea (n = 1), and/or hemosuccus pancreaticus (n = 1).
      RESULTS: All pancreatic metastases were hypervascular on imaging studies, and
      surgical removal was accomplished by pancreaticoduodenectomy (n = 3), partial
      pancreatectomy (n = 1), or subtotal pancreatectomy (n = 1). One patient died of
      disseminated disease 12 months after pancreatic resection. Two other patients had
      recurrences in the lung (n = 1) at 5 months or the pancreas/liver (n = 1) at 48
      months. Both of these patients underwent a second resection and were disease free
      at 2 and 12 months afterward. The two remaining patients were disease free at 7
      and 24 months after pancreatic resection. CONCLUSIONS: RCC is an unpredictable
      tumor that may demonstrate very late metastases even from early-stage lesions.
      Aggressive surgical management of isolated pancreatic lesions offers a chance of
      long-term survival.

PMID- 10925081
TI  - Continuous antegrade infusion of adriamycin as adjuvant therapy for upper tract
      urothelial malignancies.
AB  - OBJECTIVES: To evaluate the feasibility, efficacy, and toxicity of antegrade
      chemotherapy delivered continuously as adjuvant treatment for patients with upper
      tract transitional cell carcinoma. METHODS: During a 6-year interval, 12 patients
      with upper tract transitional cell malignancies underwent continuous antegrade
      intraluminal infusion chemotherapy (CAIIC) with adriamycin. After placement of
      percutaneous access and surgical treatment of the primary lesion, patients
      received 5-day cycles of CAIIC. Patients received between two and four treatment
      cycles at 2-week intervals. After therapy, patients with no evidence of residual
      disease were then monitored long-term with retrograde pyelography and upper tract
      cytology. RESULTS: Twelve patients underwent a total of 35 5-day cycles of CAIIC.
      No patient experienced hematologic and/or local/regional toxicity during or after
      drug infusion. Three patients were treated for upper tract carcinoma in situ, and
      9 patients had discrete exophytic tumors. Two patients died (treatment unrelated)
      before a final assessment of therapeutic outcome, leaving 10 patients available
      for evaluation of the therapeutic response. One patient with carcinoma in situ
      and 5 of 7 patients with discrete upper tract tumors remained disease free after
      surgery and adjuvant therapy. Both patients with discrete tumors in whom therapy
      failed had residual gross disease after primary surgical treatment. CONCLUSIONS:
      CAIIC using adriamycin was well tolerated for periods of up to 5 days over
      multiple cycles. Early data suggest a limited efficacy in treating patients with
      gross residual disease. The efficacy of this approach in preventing the
      recurrence of upper tract disease after surgical ablation awaits further
      assessment.

PMID- 10925082
TI  - Sexual function after vaginal surgery for stress incontinence: results of a
      mailed questionnaire.
AB  - OBJECTIVES: To address the issue of sexual dysfunction after vaginal surgery for
      incontinence based on responses to a mailed questionnaire. METHODS: A sexual
      function questionnaire was mailed to 93 women who underwent anterior vaginal wall
      suspension for stress urinary incontinence alone (group 1) or in conjunction with
      a concomitant posterior repair (group 2) at least 1 year previously. RESULTS: A
      total of 56 (60%) women responded. Following surgery, 10 (37%) women in group 1
      reported themselves as sexually active and 12 (41%) in group 2, which was similar
      to preoperative values. Only 1 woman in group 1 and 3 women in group 2 attributed
      their sexual inactivity to their own lack of desire or inability to have
      intercourse. Overall, 20% of women noted pain during intercourse, a finding
      slightly lower than the preoperative incidence (29%). No difference in the
      incidence of dyspareunia was noted between groups. Still, several women (18%)
      reported intercourse to be worse following surgery. Women who were either
      premenopausal or on hormone replacement therapy were more likely to be sexually
      active following surgery (46%) than those not on hormone replacement (17%).
      CONCLUSIONS: Overall, the percentage of women who were sexually active did not
      appear to be affected by a vaginal suspension procedure for incontinence.
      Symptomatic vaginal narrowing was rare, even among women undergoing simultaneous
      posterior repair. Still, nearly 20% of women considered intercourse to be worse
      postoperatively, although not all women reported dyspareunia. The possible causes
      for postoperative sexual dysfunction require further investigation.

PMID- 10925083
TI  - Comparison of two qualitative assays, the UBC rapid test and the BTA stat test,
      in the diagnosis of urothelial cell carcinoma of the bladder.
AB  - OBJECTIVES: To compare the diagnostic value of two rapid tests, the bladder tumor
      antigen (BTA stat) test and the newly developed urinary bladder cancer (UBC)
      Rapid test, in patients having symptoms suggestive of urothelial cell carcinoma
      (UCC) and patients being followed up after transurethral resection. METHODS: One
      hundred eighty patients with a mean age of 65.8 years (range 22 to 92) were
      included in the present study. The tests were performed on voided urine samples.
      Fifty-seven patients had symptoms suggestive of UCC and 123 patients were being
      followed up after complete transurethral resection of UCC. The voided urine was
      evaluated by the BTA stat and UBC Rapid test, which detects cytokeratins 8 and
      18. All patients underwent subsequent cystoscopic evaluation and biopsy of any
      suspicious lesion. RESULTS: In 53 patients with histologically proved UCC, the
      BTA stat had a sensitivity of 52.8% and the UBC Rapid test of 66%. According to
      the histologic stage, the sensitivity of the BTA stat was 42.8% in pTa tumors,
      61.5% in pT1, and 70% in pT2 or higher tumors. The sensitivity of the UBC test
      was 60.7% in pTa, 69. 2% in pT1, and 80% in pT2 or higher tumors. For histologic
      grades 1 to 3, the sensitivity was 38.8%, 52.6%, and 68.7% for the BTA stat and
      44.4%, 78.9%, and 75% for the UBC Rapid test, respectively. The specificity was
      70% and 90% for the BTA stat and UBC Rapid test, respectively. CONCLUSIONS: The
      UBC Rapid test was superior to the BTA stat in both sensitivity and specificity.
      Both assays are simple office procedures and require no special knowledge.
      However, they cannot replace, but only lower, the number of cystoscopies during
      the follow-up of patients with previous UCC of the bladder.

PMID- 10925084
TI  - Pilot study of the tolerability and toxicity of intravesical valrubicin
      immediately after transurethral resection of superficial bladder cancer.
AB  - OBJECTIVES: To assess in a pilot study the safety, tolerability, and technical
      feasibility of administering intravesical valrubicin immediately after
      transurethral resection of bladder tumors (TURBT) in patients with superficial
      bladder cancer and to evaluate the optimal dose of valrubicin and its systemic
      absorption. METHODS: Twenty-two patients with recurrent or newly diagnosed Stage
      Ta or T1 transitional cell tumors received a single dose of 400 mg, 600 mg, or
      800 mg of intravesical valrubicin immediately after TURBT. Four patients thought
      to be at high risk of recurrence were followed up with five additional doses of
      800 mg valrubicin, given weekly. RESULTS: The use of valrubicin after TURBT was
      generally well tolerated. Little evidence was found to suggest a direct
      relationship among the dose of valrubicin, the time between the end of TURBT and
      drug instillation, and the occurrence of most bladder symptoms. The most commonly
      reported adverse events included dysuria (77%), hematuria (59%), and
      urgency/frequency (23%). Pharmacokinetic analyses revealed that the mean systemic
      exposure to valrubicin and its metabolites depended on the extent of the TURBT
      and the damage to the bladder wall. CONCLUSIONS: The results of this study
      indicated that administration of valrubicin immediately after TURBT is feasible.

PMID- 10925085
TI  - Long-term assessment of serum vitamin B(12) concentrations in patients with
      various types of orthotopic intestinal neobladder.
AB  - OBJECTIVES: Vitamin B(12) deficiency is an important long-term problem after
      urinary diversion using an intestinal segment. In this study, we examined serum
      vitamin B(12) concentrations in patients with neobladders constructed from
      various intestinal segments to determine the anatomic factors important for
      avoiding vitamin B(12) deficiency. METHODS: Twenty-two patients (19 men and 3
      women) had an ileal neobladder (modified Studer type); 9 men had an ascending
      colonic neobladder (Goldwasser type); 30 patients (24 men and 6 women) had a
      sigmoid neobladder (modified Reddy type); and 18 (15 men and 3 women) had an
      ileocolic neobladder (Mainz type). The postoperative follow-up ranged from 3
      months to 11 years (mean +/- SD, 3.4 +/- 2.8 years). The serum vitamin B(12)
      concentration was determined at several points after surgery. RESULTS: No patient
      with a neobladder fashioned from ascending or sigmoid colon developed a low
      vitamin B(12) concentration. Of the 18 patients with an ileocolic neobladder, 3
      (16.6%) developed decreased serum vitamin B(12) concentrations after 5 to 6
      years. Of the 22 patients with an ileal neobladder, 3 (13.6%) developed a low
      serum concentration of vitamin B(12) between 9 months and 3 years after surgery.
      No patient developed megaloblastic anemia or neurologic symptoms. CONCLUSIONS:
      Preservation of the terminal 15 cm of ileum is not sufficient to ensure adequate
      vitamin B(12) absorption, and thus, preserving the ileal length is important. Use
      of colonic segments to construct neobladders appears to be preferable to ileal
      segments to preserve vitamin B(12) absorption.

PMID- 10925086
TI  - Incidental appendectomy during radical cystectomy: an interdepartmental survey
      and review of the literature.
AB  - OBJECTIVES: To survey and review the incidence of appendectomy performed during
      radical cystectomy and urinary diversion. We were interested in the reasons
      behind the decision and if continent diversions have changed the policy. METHODS:
      We performed a selective survey among urologists in academic centers throughout
      the United States regarding their practice of incidental appendectomy during
      radical cystectomy. We also reviewed the literature regarding the rationale for
      incidental appendectomy in general and during radical cystectomy in particular.
      RESULTS: Among the 13 departments and 26 urologists replying to the survey, 9
      (69%) departments and 20 (77%) individual clinicians are not performing routine
      incidental appendectomy. In 2 departments, it is considered a matter of choice,
      and, in 4 (31%) departments, appendectomy is performed routinely. Many believe
      that the low risk of subsequent appendicitis does not justify the procedure and
      that the appendix may be useful for future reconstruction. A review of the
      literature suggests that incidental appendectomy during radical cystectomy is not
      necessary. CONCLUSIONS: Incidental appendectomy during radical cystectomy is not
      necessary and is no longer being performed in many academic centers. The risk of
      subsequent appendicitis is extremely low. The decision may depend on the form of
      urinary diversion planned.

PMID- 10925087
TI  - Prevalence of urinary incontinence among institutionalized patients: a cross
      sectional epidemiologic study in a midsized city in northern Italy.
AB  - OBJECTIVES: To determine the prevalence of urinary incontinence among
      institutionalized elderly people. METHODS: A cross-sectional study was conducted
      on 839 subjects, resident in 14 residential or nursing homes. A questionnaire was
      administered to the study population and their clinical records were reviewed.
      RESULTS: The overall prevalence of urinary incontinence was 54.5%, higher in
      women (59.8%) than in men (39.2%). The prevalence increased significantly with
      age, from 26.5% in subjects 65 years old or younger to 73.7% in subjects 95 years
      old or older; with worsening of mental status, from 36.2% in well-oriented
      subjects to 76.7% in poorly oriented subjects; and with worsening of mobility,
      from 23.8% in self-sufficient subjects to 82.1% in bedridden patients. The
      prevalence was significantly associated with parity, from 54.1% in nulliparous
      women to 65.4% in multiparous women. Urinary incontinence was also associated
      with urinary tract infection, constipation, and fecal incontinence. CONCLUSIONS:
      The results of our study are in accordance with other similar studies. That more
      than one half of the elderly residents of nursing and residential homes have
      urinary incontinence shows the relevance of this condition. We believe that
      urinary incontinence in institutionalized elderly people can be managed
      essentially by measures of tertiary prevention, aimed at reducing the
      handicapping conditions and at slowing down the process of self-sufficiency
      impairment.

PMID- 10925088
TI  - Questionnaire-based assessment of bladder dysfunction in patients with mild to
      moderate Parkinson's disease.
AB  - OBJECTIVES: To assess the lower urinary tract symptoms (LUTS) in men and women
      with mild to moderate Parkinson's disease (PD) using validated symptom
      questionnaires. METHODS: Eighty men and 39 women with mild to moderate PD (Hoehn
      and Yahr score less than 3) were mailed LUTS questionnaires to complete and
      return. Men received the American Urological Association Symptom Index and women
      received the Urogenital Distress Inventory-6. Patients not responding by mail
      were called and asked to complete the survey over the telephone. Control
      populations of both symptomatic and asymptomatic men and women (without PD) were
      identified for comparison. RESULTS: The overall response rate was 78%. Men with
      early-stage PD had higher American Urological Association Symptom Index scores
      than age-matched controls (total score of 12.0 versus 7.7, P <0.05) and scores
      similar to those reported for men with symptomatic benign prostatic hyperplasia
      (12.5). Specific items noted to be higher among the men with PD included
      questions regarding frequency and urgency. Women with PD had higher scores on the
      Urogenital Distress Inventory-6 than non-age-matched controls (total score of 4.8
      versus 2.1, P <0.05), but lower scores than an age-matched group of
      neurologically intact women presenting for urologic evaluation of LUTS (6.9, P
      <0.05). CONCLUSIONS: On the basis of the responses to the validated symptom
      indexes, the development of LUTS appears to occur at an earlier stage of PD than
      was once appreciated. Prompt evaluation and treatment of patients with lower
      urinary tract complaints in the setting of PD may identify bladder dysfunction at
      an earlier, more treatable stage.

PMID- 10925090
TI  - Can prostate epithelial content predict response to hormonal treatment of
      patients with benign prostatic hyperplasia?
AB  - OBJECTIVES: There are large interindividual differences in response to medical
      therapy for men with benign prostatic hyperplasia. Selection of patients for
      alpha-blocker versus hormonal treatment is often based more on assumptions than
      on well-documented knowledge. A more scientifically based decision of therapy has
      a potential for economical savings and increased effectiveness. METHODS: We
      performed morphometry on prostate biopsy specimens and determined the amount of
      stroma, epithelium, and glandular lumen (pretreatment characteristics) in 34 men
      with benign prostatic hyperplasia before 24 weeks of androgen suppressive
      therapy. Androgen suppressive therapy consisted of either the luteinizing hormone
      releasing hormone agonist leuprolide depot (3.75 mg intramuscularly every 28
      days) or the nonsteroidal antiandrogen bicalutamide (50 mg/day orally). The
      evaluation of the clinical response (effectiveness parameters) was based on
      changes in prostate volume, peak urinary flow rate, symptom score, and bladder
      outlet obstruction. RESULTS: A large prostate volume before treatment was
      associated with more pronounced symptom score improvement, but neither prostate
      specific antigen nor any of the parameters of tissue composition used (percentage
      of epithelium, epithelial volume, and stromal/epithelial ratio) predicted a
      favorable response to hormonal treatment. CONCLUSIONS: The pretreatment variables
      that are readily available at present have a limited role in helping clinicians
      to decide the optimal medical treatment for patients with benign prostatic
      hyperplasia.

PMID- 10925089
TI  - Comparison of percent free PSA, PSA density, and age-specific PSA cutoffs for
      prostate cancer detection and staging.
AB  - OBJECTIVES: Various methods have been proposed to increase the specificity of
      prostate-specific antigen (PSA), including age-specific PSA reference ranges, PSA
      density (PSAD), and percent free PSA (%fPSA). In this multicenter study, we
      compared these methods for their utility in cancer detection and their ability to
      predict pathologic stage after radical prostatectomy in patients with clinically
      localized, Stage T1c cancer. METHODS: Seven hundred seventy-three men (379 with
      prostate cancer, 394 with benign prostatic disease), 50 to 75 years old, from
      seven medical centers were enrolled in this prospective blinded study. All
      subjects had a palpably benign prostate, PSA 4.0 to 10.0 ng/mL, and a
      histologically confirmed diagnosis. Hybritech's Tandem PSA and free PSA assays
      were used. RESULTS: %fPSA and age-specific PSA cutoffs enhanced PSA specificity
      for cancer detection, but %fPSA maintained significantly higher sensitivities.
      Age-specific PSA cutoffs missed 20% to 60% of cancers in men older than 60 years
      of age. %fPSA and PSAD performed equally well for detection (95% sensitivity) if
      cutoffs of 25% fPSA or 0.078 PSAD were used. The commonly used PSAD cutoff of
      0.15 detected only 59% of cancers. %fPSA and PSAD also produced similar results
      for prediction of the post-radical prostatectomy pathologic stage. Patients with
      cancer with higher %fPSA values (greater than 15%) or lower PSAD values (0.15 or
      less) tended to have less aggressive disease. CONCLUSIONS: The results of this
      study demonstrated that cancer detection (sensitivity) is significantly higher
      with %fPSA than with age-specific PSA reference ranges. %fPSA and PSAD provide
      comparable results, suggesting that %fPSA may be used in place of PSAD for biopsy
      decisions and in algorithms for prediction of less aggressive tumors since the
      determination of %fPSA does not require ultrasound.

PMID- 10925091
TI  - The fundamental concept, that interindividual differences among prostate glands
      can explain varying responses to treatment, remains intact. A simple test to
      pinpoint those differences remains the challenge.

PMID- 10925092
TI  - Determination of prostate-specific antigen complexed to alpha(2)-macroglobulin in
      serum increases the specificity of free to total PSA for prostate cancer.
AB  - OBJECTIVES: To determine whether prostate-specific antigen (PSA) complexed to
      alpha(2)-macroglobulin (A2M) increases the specificity of free PSA (fPSA) and
      total PSA (tPSA) for the diagnosis of prostate cancer (PCa). METHODS: In a series
      of 73 patients with PCa and 58 with benign prostatic hyperplasia (BPH), fPSA,
      tPSA, and PSA complexed with A2M (PSA-A2M) in serum were determined by specific
      immunoassays. The assay for PSA-A2M was based on the immunoadsorption of
      immunoreactive PSA in serum and the measurement of the PSA immunoreactivity
      released by denaturation of PSA-A2M at pH 11.4. RESULTS: The median proportion of
      PSA-A2M [ %PSA-A2M=PSA-A2M/(tPSA+PSA-A2M)] and that of fPSA ( %fPSA=fPSA/tPSA)
      were significantly lower in patients with PCa (8.2% and 12.4%, respectively) than
      in patients with BPH (11.6% and 22.5%, P = 0.0014 and P <0.0001, respectively).
      The median sum of %PSA-A2M and %fPSA was 22.4% in PCa and 38.2% in BPH (P
      <0.0001). When the sum of %PSA-A2M and %fPSA was used as a diagnostic test for
      PCa, 57% of patients with "falsely" elevated PSA concentrations (4 to 10 ng/mL)
      caused by BPH could be correctly identified without missing patients with PCa
      compared with 18% of the patients with BPH but not PCa using %fPSA alone.
      CONCLUSIONS: Measurement of the sum of %PSA-A2M and %fPSA in serum significantly
      improves the cancer specificity of the PSA test compared with the use of tPSA and
      %fPSA.

PMID- 10925093
TI  - Calculated volume of prostate cancer identifies patients with clinical stage T1C
      disease at high risk of biochemical recurrence after radical prostatectomy: a
      preliminary study.
AB  - OBJECTIVES: To evaluate whether the calculated volume of prostate cancer (cVca)
      in patients with clinical Stage T1c prostate cancer who were treated surgically
      was a good predictor of biochemical disease-free prostate-specific antigen (PSA)
      recurrence. METHODS: Between 1990 and 1996, patients with prostate cancer who
      were surgically treated for clinical Stage T1c at Brigham and Women's Hospital
      were retrospectively evaluated, and 188 patients (median PSA 6.9 ng/mL) were
      included in this study. cVca (determined by cancer-specific PSA, prostate volume,
      and Gleason grade), pathologic stage, and time to PSA failure were assessed.
      RESULTS: cVca correlated strongly with the preoperative PSA level (P <0.00001,
      chi-square test), Gleason grade (P <0.00001), and pathologic stage (P <0.00001).
      Kaplan-Meier curves for PSA disease-free survival were constructed for patients
      with cVca less than 0.5 cm(3) (group 1), cVca of 0.5 to 4.0 cm(3) (group 2), and
      cVca greater than 4.0 cm(3) (group 3). The 2-year PSA disease-free survival rate
      was 100%, 81%, and 36% for groups 1, 2, and 3, respectively (P <0.0001). Cox
      multiple regression analysis demonstrated that cVca was superior to PSA and
      Gleason score for determination of serologic PSA failure after surgery.
      CONCLUSIONS: Our results demonstrated that cVca is a good predictor of
      biochemical recurrence in patients with clinical Stage T1c prostate cancer.
      Perhaps, after validation by others, cVca can serve as a tool in choosing various
      treatment options for prostate cancer.

PMID- 10925094
TI  - Usefulness of age-specific reference range of prostate-specific antigen for
      Japanese men older than 60 years in mass screening for prostate cancer.
AB  - OBJECTIVES: To investigate the age-specific reference range of prostate-specific
      antigen (PSA) in Japanese men older than 60 years of age by analyzing the
      receiver operating characteristic (ROC) curve. Several reports have noted that
      many clinically serious cancers are missed by raising the cutoff value of the age
      specific PSA reference range for men older than 60 years. METHODS: We studied
      6744 individuals who had undergone mass screening for prostate cancer in Gunma
      Prefecture from 1994 to 1998. PSA determination was the first step of the mass
      screening in all subjects. Digital rectal examination and transrectal
      ultrasonography (TRUS) were performed in all except in a fraction of patients.
      Subjects with an abnormal PSA level or abnormal digital rectal examination or
      TRUS findings underwent TRUS-guided systematic sextant biopsies. Patients older
      than 60 years of age were grouped according to their age at 5-year intervals, and
      the cutoff value of the age-specific PSA reference range was calculated for each
      age group by analyzing the ROC curve. RESULTS: The diagnostic efficiency of the
      age-specific PSA reference range was optimal with cutoff values of 3.0, 3.5, 4.0,
      4.0, and 7.0 ng/mL in subjects 60 to 64, 65 to 69, 70 to 74, 75 to 79, and older
      than 80 years of age, respectively. By using the age-specific PSA reference range
      as determined by the ROC curve, the sensitivity, specificity, and efficiency
      increased to 92.4%, 91.2%, and 84.3%, respectively. When the standard PSA
      reference range was used for the diagnosis, the sensitivity, specificity, and
      efficiency was 89.1%, 92.4%, and 82.3%, respectively. All of the cases of
      prostate cancer detected by using the age-specific PSA reference range with the
      cutoff point based on the ROC curves were clinically significant. CONCLUSIONS:
      The age-specific PSA reference range cutoff value in this setting demonstrated
      better diagnostic efficiency than the standard cutoff value of PSA and the age
      specific PSA reference range determined by the 95% confidence interval. It
      appears likely to be a useful diagnostic index for the first step of mass
      screening in Japanese men.

PMID- 10925095
TI  - Adenocarcinoma of the prostate invading the seminal vesicle: prognostic
      stratification based on pathologic parameters.
AB  - OBJECTIVES: To stratify the prognosis of lymph node-negative, seminal vesicle
      positive tumors in men with prostate cancer after radical retropubic
      prostatectomy. METHODS: Sixty cases were analyzed for multiple parameters and
      correlated with postoperative biochemical (prostate-specific antigen)
      progression. Variables included Gleason score, primary Gleason pattern,
      percentage of Gleason pattern 4, any presence of Gleason pattern 5, method of
      seminal vesicle invasion (SVI), margin positivity, SVI extent, SVI bilaterality,
      vascular invasion, extent of extraprostatic extension, length of tumor extending
      along the seminal vesicles, presence of intraductal carcinoma within the
      prostate, bladder neck margin positivity, and tumor volume. RESULTS: We were able
      to stratify the prognosis based on the combination of a variation of the Gleason
      score and margin status and vascular invasion status. Using this stratification,
      a few patients had an excellent long-term prognosis, with most patients split
      into two groups, one experiencing rapid and the other slower progression.
      CONCLUSIONS: SVI is not associated with a uniformly poor prognosis. Rather,
      tumors can be substratified by pathologic parameters into groups with differing
      prognoses based on routine histologic examination.

PMID- 10925096
TI  - Long-term neoadjuvant hormone therapy prior to radical prostatectomy: evaluation
      of risk for biochemical recurrence at 5-year follow-up.
AB  - OBJECTIVES: To assess the effects of 8 months of neoadjuvant therapy on
      pathologic stage and biochemical recurrence rates. METHODS: One hundred fifty-six
      men with clinically localized prostate cancer were treated with neoadjuvant
      combined androgen withdrawal therapy for 8 months prior to radical prostatectomy.
      Preoperative clinical stage, Gleason score, and serum prostate-specific antigen
      (PSA) levels were compared with treatment outcome (pathologic stage and PSA
      recurrence). RESULTS: PSA at diagnosis was 10 microg/L or higher in 36% with a
      mean of 11.5 microg/L. Clinical stage was T1c in 18%, T2 in 74%, and T3a in 8%.
      Gleason score was 6 or lower in 76% and 7 or higher in 24%. Pathologic stage was
      T0 in 13%, T2 in 66%, T3 (specimen confined) in 13%, T3 (margin positive) in 6%,
      and TxN+ in 2%. Incidence of positive margins increased with clinical stage T3a
      versus organ-confined disease (25% versus 4%, P <0.05), pretreatment Gleason
      scores 7 or higher versus Gleason scores 6 or lower (11% versus 4%, P = NS), and
      pretreatment PSA levels higher than 10 microg/L compared with PSA levels lower
      than 10 microg/L (15% versus 0%, P <0.01). Overall PSA recurrence rate was 12.2%
      after a mean postoperative follow-up of 54 months. Risk of PSA recurrence
      increased with clinical stage (25% T3 versus 11% organ confined, P <0.01),
      pretreatment PSA (7% if PSA lower than 10 microg/L versus 21% if 10 microg/L or
      higher, P <0.02), Gleason score (9% if 6 or lower versus 22% if 7 or higher, P
      <0.02), and pathologic stage (6% of pT2, 24% of pT3M-, and 56% of pT3M+, P
      <0.01). PSA recurrences occurred in 6% of patients with no adverse preoperative
      risk factors, 12% with any one of the high-risk factors, and 29% with any two of
      the high-risk factors. CONCLUSIONS: Risk of PSA recurrence after 8 months of
      neoadjuvant therapy is low after 5 years of follow-up and remains proportional to
      the presence of adverse preoperative risk factors. Prospective randomized studies
      are required to determine whether longer duration of neoadjuvant therapy reduces
      the risk of biochemical recurrence after radical prostatectomy.

PMID- 10925097
TI  - Prostate cancer detection, characterization, and clinical outcomes in men aged 70
      years and older referred for transrectal ultrasound and prostate biopsies.
AB  - OBJECTIVES: To evaluate the diagnostic findings and treatment options chosen in
      men aged 70 years and older referred for prostate biopsy. METHODS: Age, prostate
      specific antigen (PSA), biopsy pathology, clinical stage, treatment pursued, and
      treatment outcome were analyzed in 210 men age 70 years and older referred for
      transrectal ultrasound and prostate biopsies. All patients were followed for a
      mean of 46.9 months (range 28 to 63). RESULTS: Cancer was found in 120 (56.8%) of
      the patients. The cancer detection rate was significantly higher (81.0%) in
      patients aged 80 years and older than those younger than 80 years. Cancer
      patients aged 80 years and older had a higher rate of poorly differentiated
      cancer (64.7%) compared with the 70 to 74-year-olds (33.3%) and 75 to 79-year
      olds (32.1%). The patients aged 80 years and older also had a larger proportion
      of high-stage cancer. The patients younger than 80 years had a significantly
      higher incidence of stable/falling PSA with treatment compared with the older
      patients. Of the 210 patients, 41 (19.4%) died within 5 years of the diagnostic
      procedure; 3 died of prostate cancer. The death rate was not significantly
      different among the three age groups evaluated. None of the patients aged 80
      years and older died of prostate cancer. CONCLUSIONS: Patients aged 80 years and
      older who are diagnosed with prostate cancer are less likely to respond well to
      treatment and usually die of unrelated causes. Aggressive diagnosis, staging, and
      treatment in octogenarians should be guided by the patients' symptoms, overall
      health, and personal preferences.

PMID- 10925098
TI  - Modifiable risk factors and erectile dysfunction: can lifestyle changes modify
      risk?
AB  - OBJECTIVES: To prospectively examine whether changes in smoking, heavy alcohol
      consumption, sedentary lifestyle, and obesity are associated with the risk of
      erectile dysfunction. METHODS: Data were collected as part of a cohort study of a
      random sample of men 40 to 70 years old, selected from street listings in the
      Boston Metropolitan Area, Massachusetts. In-home interviews were completed by
      1709 men at baseline in 1987 to 1989 and 1156 men at follow-up in 1995 to 1997
      (average follow-up 8.8 years). Analyses included 593 men without erectile
      dysfunction at baseline, who were free of prostate cancer, and had not been
      treated for heart disease or diabetes. The incidence of moderate to complete
      erectile dysfunction was determined by discriminant analysis of responses to a
      self-administered sexual function questionnaire. RESULTS: Obesity status was
      associated with erectile dysfunction (P = 0.006), with baseline obesity
      predicting a higher risk regardless of follow-up weight loss. Physical activity
      status was associated with erectile dysfunction (P = 0.01), with the highest risk
      among men who remained sedentary and the lowest among those who remained active
      or initiated physical activity. Changes in smoking and alcohol consumption were
      not associated with the incidence of erectile dysfunction (P >0.3). CONCLUSIONS:
      Midlife changes may be too late to reverse the effects of smoking, obesity, and
      alcohol consumption on erectile dysfunction. In contrast, physical activity may
      reduce the risk of erectile dysfunction even if initiated in midlife. Early
      adoption of healthy lifestyles may be the best approach to reducing the burden of
      erectile dysfunction on the health and well-being of older men.

PMID- 10925099
TI  - Conservative treatment of phimosis in children using a topical steroid.
AB  - OBJECTIVES: From 1997 through 1998, we conducted a prospective study to evaluate
      the long-term outcome of using topical steroids in the treatment of childhood
      phimosis. METHODS: Both the parents and their children were instructed to apply
      0.05% betamethasone cream topically twice a day for 1 month and to retract the
      prepuce after the fifth day of treatment. Results were evaluated at the end of
      the treatment and 6 months later. RESULTS: One hundred thirty-seven boys were
      evaluated. The median age was 5.4 years. At initial presentation, 61 boys had a
      phimotic but retractable prepuce, 37 had a nonretractable phimotic ring, and 39
      had a pinpoint opening. Patients with a history of previous forcible foreskin
      retractions were considered to have secondary phimosis. By 6 months following
      treatment, 90% (124 children) had an easily retractable prepuce without a
      phimotic ring. No differences were seen in the response rate between those with
      primary and secondary phimosis. In all cases, the treatment was well tolerated
      without local or systemic side effects. All the patients with persistent or
      recurrent phimosis were found to be noncompliant with the suggested daily
      foreskin care. CONCLUSIONS: Topical steroid for the treatment of phimosis is a
      safe, simple, and inexpensive procedure that avoids surgery and its associated
      risks. It is effective both in primary and in secondary phimosis. We emphasize
      the importance of proper and regular foreskin care and hypothesize on the
      mechanism of action of the steroids.

PMID- 10925100
TI  - Increased urinary transforming growth factor-beta(1) excretion in children with
      posterior urethral valves.
AB  - OBJECTIVES: Patients with posterior urethral valves (PUV) are at significant risk
      for progression to end-stage renal disease, despite early correction of the
      obstruction. Experimental models of urinary obstruction demonstrate increased
      renal expression of the profibrotic inflammatory mediator, transforming growth
      factor-beta(1) (TGF-beta(1)). Urinary TGF-beta(1) excretion is elevated in
      certain glomerular diseases, but has not been well studied in patients with
      obstructive lesions. The objective of this study was to examine urinary TGF
      beta(1) excretion in children with PUV. METHODS: Fourteen patients with PUV, aged
      3.2 to 14.5 years, with estimated glomerular filtration rates (GFRs) of 12.8 to
      139 mL/min/1.73 m(2) were enrolled. Sixteen normal subjects (9 male, 7 female),
      aged 4.3 to 20.5 years, served as controls. Total urinary TGF-beta(1)
      concentration was assayed by enzyme-linked immunoabsorbent assay, and expressed
      as a ratio to urinary creatinine concentration. RESULTS: Urinary TGF-beta(1)
      excretion was significantly greater in patients with PUV (range 0 to 0.063,
      median 0.019 ng/mg urine creatinine) compared with that of healthy controls
      (range 0 to 0.022, median 0.005 ng/mg urine creatinine) (P <0.01). There was no
      correlation between urinary TGF-beta(1) excretion and estimated GFR, past urinary
      diversion surgery, or bladder wall thickening. Among healthy controls, urinary
      TGF-beta(1) was not correlated with age or gender. CONCLUSIONS: Results from this
      study suggest that TGF-beta(1) may contribute to progressive renal insufficiency
      in patients with PUV. Further studies are indicated to determine if agents that
      affect TGF-beta(1) expression, such as angiotensin-converting enzyme inhibitors,
      can slow the progression of renal disease in PUV.

PMID- 10925101
TI  - Although tremendous advances are being made in our understanding of the specific
      factors responsible for regulating pathologic changes in organ injury, using this
      information to answer clinical diagnostic and prognostic questions in urology
      often remains difficult.

PMID- 10925102
TI  - A new suprapubic cystostomy trocar system.
AB  - We describe a newly developed suprapubic catheterization set with a defined
      sigmoidal, geometrically and functionally tripartite tip and grooved trocar
      shaft. The device was designed to enhance the handling and safety features of the
      current commercially available sets to promote the broader application of
      suprapubic catheterization.

PMID- 10925103
TI  - Retrograde perfusion sphincterometry with a flexible cystoscope: method of
      troubleshooting the AMS 800.
AB  - We developed the technique of retrograde perfusion sphincterometry to
      troubleshoot the AMS 800 device. We implanted artificial urinary sphincters in
      men who were incontinent after prostatectomy and performed intraoperative
      retrograde perfusion sphincterometry. Retrograde perfusion sphincterometry using
      a flexible cystoscope is simple and allows early recognition of intraoperative
      urethral injury and mechanical malfunction.

PMID- 10925104
TI  - Transvaginal repair of postcystectomy peritoneovaginal fistulae.
AB  - To our knowledge, peritoneovaginal fistula is a complication of cystectomy that
      has not been reported before. We describe 2 patients in whom a transvaginal
      approach using a Martius flap was utilized to repair persistent vaginal leakage
      after cystectomy. At a mean follow-up of 20 months, both patients are free from
      vaginal leakage and have no evidence of recurrent fistula. This approach offers a
      safe and effective way to repair a peritoneovaginal fistula in a cystectomy
      patient.

PMID- 10925105
TI  - Percutaneous endopyelotomy.
AB  - OBJECTIVES: During the past 10 years, numerous reports around the world have
      documented the safety and success rate of antegrade endopyelotomy. We describe
      the classic endopyelotomy in conjunction with some new alternatives for making
      the incision. TECHNICAL CONSIDERATIONS: Antegrade endopyelotomy is performed
      through the 0.5-in. incision of the percutaneous nephrostomy created by way of an
      upper or middle calix. Using the hook-shaped cold knife, an endopyelotome is
      positioned, and the entire procedure can be performed under direct vision, which
      determines the exact position, depth, and extent of the incision. The
      ureteropelvic junction (UPJ) obstruction is incised in a posterolateral position,
      and the hook is withdrawn from the proximal ureter. Using nephroscopic scissors,
      a small full-thickness puncture is made into the renal pelvis and then the
      scissors is opened, under constant visual control, until it reaches the
      peripelvic space. The section of the pelvic wall is completed with the scissors
      running through the UPJ, without any interchange of the nephroscope. A holmium
      laser has been also used, with the 365-microm fiber introduced through a stent
      pusher. Under direct vision, the UPJ is incised with fiber, permitting
      observation and coagulation of bleeding from small vessels. After the procedure,
      either a 14-8.2F endopyelotomy stent or a 14-7F tapered endoureterotomy stent is
      placed over the guidewire. CONCLUSIONS: Percutaneous antegrade endopyelotomy is a
      safe and effective treatment of UPJ obstruction for most patients, regardless of
      the method used to perform the incision.

PMID- 10925107
TI  - Marjolin's ulcer of the suprapubic cystostomy site infiltrating the urinary
      bladder: a rare occurrence.
AB  - We report a case of a 40-year-old man who had presented with a spontaneous
      suprapubic urinary leak from a well-healed suprapubic cystostomy tract scar, 20
      years following a successful scrotal tube substitution urethroplasty done for a
      post-traumatic urethral stricture. Preoperative contrast studies suggested a
      recurrent bulbomembranous urethral stricture. Excision biopsy of the suprapubic
      fistulous tract revealed scar cancer infiltrating the bladder wall. Of 3 similar
      cases reported in the past, only 1 had bladder involvement. Ours is the second
      such case with bladder involvement.

PMID- 10925106
TI  - Prostatic laceration associated with blunt pelvic trauma.

PMID- 10925108
TI  - Abdominal wall hernia: an uncommon complication of in utero vesicoamniotic shunt
      placement.
AB  - Three cases are reported in which placement of a vesicoamniotic shunt in utero
      for the treatment of obstructive uropathy led to the rare complication of
      abdominal wall hernia. All 3 patients underwent vesicoamniotic shunt placement
      for severe oligohydramnios and a markedly dilated bladder in an effort to
      preserve renal function and to prevent pulmonary hypoplasia. All three shunts
      were initially placed at or above the umbilicus. The abdominal wall hernias were
      closed postnatally at the time of temporary vesicostomy for urethral obstruction.
      All 3 patients had sufficient pulmonary development, but 2 of 3 had renal
      failure, requiring dialysis. Management and potential etiology of this rare
      complication are discussed.

PMID- 10925109
TI  - Hematospermia as the presenting symptom of metastatic malignant melanoma of
      unknown primary origin.
AB  - The presence of blood in the ejaculate is alarming to patients and may arise from
      many sources in the genitourinary tract. Fortunately, hematospermia is rarely due
      to underlying malignancy and only necessitates further evaluation with continued
      symptoms. We report a case of persistent hematospermia in a man with human
      immunodeficiency virus caused by metastatic malignant melanoma to both seminal
      vesicles. The evaluation included pelvic magnetic resonance imaging and
      transrectal ultrasound-guided biopsy. Metastases to the brain were subsequently
      discovered, but a primary source for the melanoma could not be identified. This
      is the first reported case of isolated involvement of the seminal vesicles with
      malignant melanoma and underscores the potential for serious disease presenting
      as hematospermia.

PMID- 10925110
TI  - Tricuspid valve metastasis from testicular carcinoma: a case report and review of
      the literature.
AB  - A 20-year-old man with Stage II nonseminomatous germ cell tumor underwent
      chemotherapy and multiple surgical resections of recurrent abdominal and
      supradiaphragmatic mature teratomas. Evaluation of a new heart murmur led to the
      diagnosis of tricuspid valve teratoma, which required complete valve excision and
      replacement. We present our experience with the first discrete tricuspid valve
      metastasis from testicular carcinoma and review the literature regarding cardiac
      metastases from germ cell neoplasms.

PMID- 10925111
TI  - Metastatic osteomyelitis after pubovaginal sling using bone anchors.
AB  - We report a case of osteomyelitis with metastasis to the T10 vertebra related to
      bone anchor use with pubovaginal sling. The morbidity was significant: long-term
      intravenous antibiotics, multiple surgeries to correct the problem, and
      subsequent chronic pelvic pain. Given that this complication is unheard of after
      standard fascia or allograft sling, consideration should be given before bone
      anchor use in women at risk for wound infection (diabetes, obesity, or
      reoperation). Minimally, patients should be told of the possibility of this
      severe complication in the informed consent with bone anchor use.

PMID- 10925112
TI  - Duplicated exstrophy in one of identical twins.
AB  - The characteristic of duplicated exstrophy is the presence of a patch of
      exstrophic bladder mucosa in the infraumbilical region with a low-set umbilicus,
      in addition to the normal bladder. Musculoskeletal defects, diastasis pubis, and
      rectus abdominis can also be found in these patients. We report the first case of
      a female twin baby with appearance of a low-set umbilicus and diastasis pubis
      associated with a pubic sinus. The external genitalia and urinary continence were
      normal. Duplicated exstrophic mucosal remnant was excised, and the
      histopathologic study of the specimen confirmed urothelium.

PMID- 10925113
TI  - Petroleum jelly lipogranuloma of the penis treated with excision and native skin
      coverage.
AB  - Penile augmentation by injection of petroleum jelly is still performed by
      nonmedical practitioners abroad and causes foreign body reactions with resultant
      scarring, deformity, and ulceration. Surgical treatment involves removal of the
      foreign material and granuloma, followed by scrotal flaps, inguinal flaps, free
      flaps, or split-thickness skin grafts. We present the use of native penile skin
      for coverage after resection of oleogranuloma in the first case of which we are
      aware. Local penile skin coverage allows for an excellent surgical result, with
      many potential advantages over flaps or skin grafts.

PMID- 10925114
TI  - Evidence for elevated telomerase activity in small cell carcinoma of the bladder.
AB  - Telomerase activity was found to be elevated using a quantitative assay on snap
      frozen protein extracts of exfoliated cells in urine and bladder washings and
      tumor tissue obtained from a male patient with small cell carcinoma of the
      bladder. To the best of our knowledge, this is the first demonstration of
      elevated values of telomerase activity in genitourinary small cell carcinoma and
      is in keeping with the findings in primary lung locations.

PMID- 10925116
TI  - Spermatic cord rhabdomyoma.
AB  - A 67-year-old man presented with a scrotal swelling. Intraoperatively, this
      swelling was found to arise from the spermatic cord structures and was completely
      excised. Histopathology revealed a rhabdomyoma arising from the cord. The patient
      has had no evidence of recurrence in the past 24 months. We present the various
      types of rhabdomyomas and discuss the differential diagnosis for a spermatic cord
      swelling.

PMID- 10925115
TI  - Molecular diagnosis of metastatic origin in a patient with metachronous multiple
      cancers of the renal pelvis and bladder.
AB  - It is not uncommon for patients with urothelial cancer to have synchronous and
      metachronous multifocal invasive tumors of the bladder and upper urinary tract.
      If a metastatic lesion becomes evident in such a patient, the origin of the
      metastasis is often not determinable using conventional histopathologic
      examination of the surgical or autopsy specimen. Here, we report a patient in
      whom the clonal relationship among the histologically undistinguishable
      multifocal urothelial cancers and metastatic tumors could be clarified by
      molecular genetic analysis. Furthermore, the potential role for each genetic
      alteration in the multifocal and metastatic tumor development and the treatment
      efficacy for each multifocal tumor were also clearly demonstrated.

PMID- 10925117
TI  - Unilateral hydronephrosis resulting from intraluminal obstruction of the ureter
      by adenosquamous endometrioid carcinoma arising from disseminated endometriosis.
AB  - A case of adenosquamous carcinoma arising in the background of disseminated
      pelvic endometriosis presented as unilateral hydronephrosis and a polypoid
      intraluminal ureteral mass. This is the first case of a malignancy arising in
      endometriosis presenting as an obstructive ureteral mass. The patient had a
      history of total hysterectomy and bilateral salpingo-oophorectomy 5 years earlier
      because of an endometriotic cyst, and had since been under unopposed estrogen
      replacement therapy. An analysis of the case and related literature is presented.
      Possible pathogenic mechanisms are discussed.

PMID- 10925118
TI  - Synergistic chemosensitization and inhibition of tumor growth and metastasis by
      adenovirus-mediated P53 gene transfer in human bladder cancer model.
AB  - OBJECTIVES: To determine whether an adenovirus-mediated p53 gene (Ad5CMV-p53)
      transfer enhances cisplatin cytotoxicity in vitro and whether Ad5CMV-p53 and
      cisplatin synergistically inhibit growth and metastasis in vivo using human
      bladder cancer KoTCC-1 cells. METHODS: MTT assays and DNA fragmentation assays
      were used to examine the effects of treatment with Ad5CMV-p53 and/or cisplatin on
      growth inhibition and induction of apoptosis, respectively, in KoTCC-1 cells. The
      efficacies of combined Ad5CMV-p53 and/or cisplatin therapy against growth and
      metastasis of KoTCC-1 tumors were assessed using subcutaneous and orthotopic
      tumor cell injection models. RESULTS: Ad5CMV-p53 substantially enhanced cisplatin
      chemosensitivity in a dose-dependent manner, reducing the median IC(50) by more
      than 50%. Characteristic apoptotic DNA laddering was induced by the combination
      of sublethal doses of Ad5CMV-p53 and cisplatin, but not by either agent alone.
      Furthermore, combined Ad5CMV-p53 and cisplatin therapy synergistically inhibited
      growth of subcutaneous KoTCC-1 tumors and the incidence of metastasis after
      orthotopic injection. CONCLUSIONS: These findings illustrate that combined
      treatment with Ad5CMV-p53 and cisplatin could be an attractive strategy for
      inhibiting progression of bladder cancer through effective induction of
      apoptosis.

PMID- 10925119
TI  - Relationship between flow cytometric DNA ploidy and nuclear grade with endocrine
      dysfunction in adrenal cortical adenomas.
AB  - OBJECTIVES: To determine the relationship among the DNA ploidy, histopathologic
      features, and clinical syndrome in adrenal cortical adenomas, because the cells
      often show variability in nuclear size and configuration. METHODS: Our study
      included 44 adenomas associated with primary aldosteronism and 23 adenomas
      associated with Cushing syndrome. Normal adrenal glands from patients with renal
      carcinoma served as the controls. Paraffin-embedded tissues were examined for DNA
      content by flow cytometry. The mean percentage of G(2)/M (4C%) of the control
      samples was 3.8%. Tetraploid was represented by a histogram with both a 4C peak
      greater than 9% (mean + 2.4 SD of control samples) and a small 8C peak. RESULTS:
      Flow cytometric analysis revealed diploidy in 30, tetraploidy in 27, and
      aneuploidy in 8 of the 67 adenomas; 2 adenomas could not be classified. All 17
      normal adrenal glands showed diploidy. A significant relationship was noted
      between DNA ploidy and the clinical syndrome (ie, a larger proportion of adenomas
      with primary aldosteronism had a tetraploid DNA histogram compared with adenomas
      with Cushing syndrome, P <0. 0001). Adenomas with primary aldosteronism had a
      significantly higher nuclear grade (III or IV) than did tumors with Cushing
      syndrome (P = 0.033). A significant relationship was also observed between DNA
      ploidy and nuclear grade in 57 euploid tumors, with tetraploid tumors often
      showing the highest nuclear grade (P = 0. 037). CONCLUSIONS: Our results have
      demonstrated that adrenal cortical adenomas associated with primary aldosteronism
      often reveal severe nuclear pleomorphism, indicating that nuclear pleomorphism
      might be due to a tetraploid stemline.

PMID- 10925120
TI  - Analysis of the mechanism of discrepant nuclear morphometric results comparing
      preoperative biopsy and prostatectomy specimens.
AB  - OBJECTIVES: To explore the mechanism for the differing nuclear morphometric
      results between needle biopsy and surgical specimens of the prostate. METHODS: In
      experiment 1, a comparison of mean nuclear area (MNA), volume-weighted mean
      nuclear volume (MNV), and form factor (FF) for prostatic epithelial cells was
      performed between preoperative needle biopsy and prostatectomy specimens from 5
      patients with benign prostatic hyperplasia (BPH). In experiment 2, a scheduled,
      sequential ex vivo needle sampling from the enucleated prostates (at 0, 2, 6, and
      24 hours after surgical resection) was also performed for 7 patients with BPH.
      The prostatectomy specimens were left unfixed for 2 hours until the second needle
      sampling was done. Nuclear morphometric parameters were measured on the needle
      sampled as well as on the prostatectomy specimens. RESULTS: MNA, MNV, and FF of
      BPH cells measured on preoperative biopsy specimens were smaller than those of
      surgical specimens in all 5 of the cases. The results of nuclear morphometry on
      the materials obtained by ex vivo needle sampling of prostates before and during
      fixation revealed that the MNA, MNV, and FF for BPH cells of 0-hour specimens
      were significantly smaller than those for needle samples at 2, 6, and 24 hours
      after surgical resection as well as those for prostatectomy specimens.
      CONCLUSIONS: The present study provided further evidence that the ischemic damage
      caused by delayed fixation could result in a substantial change of the nuclear
      morphology of prostate cells. An immediate start, as well as a rapid completion,
      of the fixation procedure seems critical for an accurate nuclear morphometry of
      prostatectomy specimens.

PMID- 10925121
TI  - Modulation of apoptotic and inflammatory genes by bioflavonoids and angiotensin
      II inhibition in ureteral obstruction.
AB  - OBJECTIVES: Ureteral obstruction results in an injury response that can progress
      to irreversible renal fibrosis and tubular atrophy by apoptosis. The molecular
      events leading to apoptosis from obstruction are not well understood. We
      investigated the effect of bioflavonoids and angiotensin II inhibition on
      apoptotic and inflammatory gene expression in a model of unilateral ureteral
      obstruction (UUO). METHODS: Complete UUO was produced in rats by ureteral
      ligation. The rats were treated with dimethyl sulfoxide (control), enalapril,
      losartan, curcumin, or quercetin. The animals were killed on day 7 and both
      obstructed and contralateral unobstructed kidneys were harvested. Expression of
      the inflammatory chemokine monocyte chemotactic protein-1, apoptosis effector
      genes Fas and Fas ligand, and oxidative stress gene HO-1 was evaluated by reverse
      transcriptase-polymerase chain reaction. RESULTS: Ureteral obstruction was
      associated with a 6.3-fold increase in monocyte chemotactic protein-1 expression
      compared with sham-operated rats (P = 0.01). Monocyte chemotactic protein-1
      expression was severely attenuated in all other treatment groups (P <0.05).
      Similarly, Fas and Fas ligand expression were increased in control UUO kidneys
      compared with sham-operated ones (P <0.05). Fas gene expression was significantly
      inhibited by quercetin but not enalapril, losartan, or curcumin compared with the
      control. The induction of Fas ligand was attenuated in all treatment groups (P
      <0.05). HO-1 was expressed at low levels in both unobstructed and obstructed
      kidneys. Treatment with curcumin increased HO-1 expression fourfold (P <0.05).
      CONCLUSIONS: The expression of apoptotic and chemokine genes is significantly
      upregulated in UUO. Bioflavonoids and angiotensin inhibitors are able to
      attenuate the expression of these genes and thus may be beneficial in renal
      protection.

PMID- 10925124
TI  - The electrostability and electrically assisted delivery of an organophosphate
      pretreatment (physostigmine) across human skin in vitro.
AB  - Physostigmine is a tertiary carbamate that is utilised as a pretreatment against
      organophosphate intoxication. Oral delivery of physostigmine is not practical due
      to high first pass metabolism and short elimination half life. Transdermal
      administration of physostigmine may circumvent such problems. The aim of this
      study was to assess the electrostability of physostigmine and the feasibility of
      electrically assisted transdermal drug delivery of physostigmine through isolated
      human skin in vitro. Buffered solutions of physostigmine (free base, salicylate
      and sulphate) were electrostable under conditions of iontophoresis and
      electroporation as measured by HPLC, although instability of the chloridised
      silver electrodes was observed. Physostigmine sulphate was chosen for further
      study as it appeared to prevent degradation of the electrodes. Under conditions
      of iontophoresis (0.8 mA cm(-2), applied for 5- or 2.5-min durations for a
      maximum period of 45 min over 8 h), the total quantity of physostigmine sulphate
      that penetrated was 6.5+/-2.3% and 3.9+/-1.7% (pH 5.0 and pH 5.5) of the total
      applied dose (2 mg). Physostigmine did not penetrate the skin when electroporated
      at a frequency of 0.1 Hz or 10 Hz (100 V, 1 ms pulse width, duration 1 s,
      repetition 5-10 s), but significant amounts were delivered at a frequency of 100
      Hz, being 11.3+/-2.9% and 5.8+/-2.5% of the applied dose (pH 5.0 and pH 5.5,
      respectively). These data indicate that iontophoretic and electroporative drug
      delivery of physostigmine sulphate was buffer-dependent, an effect tentatively
      attributed to a combination of co-ion competition, mono/di-cation ratio and
      applied charge effects.

PMID- 10925123
TI  - Nifedipine controlled delivery by sandwiched osmotic tablet system.
AB  - The sandwiched osmotic tablet system (SOTS), which is composed of a sandwiched
      osmotic tablet core surrounded by a cellulose acetate membrane with two orifices
      on both side surfaces, has been successfully prepared with the purpose of
      delivering nifedipine. The sandwiched osmotic tablet core consists of a middle
      push layer and two attached drug layers. Influences of tablet formulation
      variables, orifice size and membrane variables on nifedipine release of SOTS have
      been studied. It was found that potassium chloride amount of push layer and
      polyethylene oxide amount of drug layer had markedly positive effects on
      nifedipine release. A push layer/drug layer co-controlled osmotic delivery
      mechanism and the optimal core formulation have been proposed. The appropriate
      orifice size was observed in the range of 0.50-1.41 mm. It was also found that
      the drug release rate of SOTS could be increased by incorporating hydrophilic
      plasticizer in the membrane, whereas it decreased with hydrophobic plasticizer.
      It has been observed that the SOTS gives fairly comparable in vitro release
      features as that of commercialized push-pull osmotic tablet system, such as an
      approximately constant rate up to 24 h and independence of release media and
      agitation rate. Exempting side identification before drilling, it is easier to
      prepare the SOTS than the push-pull osmotic tablet system.

PMID- 10925125
TI  - Drug release characteristics of unimolecular polymeric micelles.
AB  - Biodegradable, unimolecular polymeric micelles possess several features that are
      attractive for drug delivery applications: Thermodynamic stability, ability to
      encapsulate and solubilize a hydrophobic guest molecule, biodegradability, as
      well as size and surface characteristics that prevent rapid clearance by the RES.
      Here we investigate the potential of these unimolecular polymeric micelles to
      release a drug for an extended time. Lidocaine was used as a model drug for in
      vitro studies using a horizontal diffusion cell and cellulose membrane that
      prevented polymer transport from the source to the receiver compartment. The
      transport of free lidocaine from source to receiver under sink conditions was
      zero-order and complete within 8 h. The transport of lidocaine initially
      encapsulated in polymer was zero-order for the first 14 h, and 96% of the
      lidocaine was detected within 24 h.

PMID- 10925126
TI  - Formula optimization of theophylline controlled-release tablet based on
      artificial neural networks.
AB  - Formulation of the controlled-release tablet containing theophylline was
      optimized based on the simultaneous optimization technique in which an artificial
      neural network (ANN) was incorporated. As model formulations, 16 kinds of
      theophylline tablets were prepared. The amounts of Controse, the mixture of
      hydroxypropylmethyl cellulose with lactose, cornstarch and compression pressure
      were selected as causal factors. The release profiles of theophylline were
      characterized as the sum of the fast and slow release fractions. The initial
      weight, the rate constant in the fast release fraction and the rate constant in
      the slow release fraction were estimated as release parameters. A set of release
      parameters and causal factors were used as tutorial data for ANN and analyzed
      using a computer. Based on the plasma concentration profiles of theophylline
      predicted by the pharmacokinetic analysis in humans, a desirable set of release
      parameters was provided. The simultaneous optimization was performed by
      minimizing the generalized distance between the predicted values of each response
      and the desirable one that was optimized individually. The optimization technique
      incorporating ANN showed a fairly good agreement between the observed values of
      release parameters and the predicted results.

PMID- 10925127
TI  - A novel nonviral vector based on vesicular stomatitis virus.
AB  - Here we report a simple and efficient method for nonviral gene transfer using
      liposomes which have envelope protein of vesicular stomatitis virus (VSV) on
      their surface (VSV-liposomes). We prepared VSV-liposome by fusing simple
      liposomes with VSV particles. The density of VSV-liposome fusion products was
      intermediated between that of liposomes and that of VSV particles. Furthermore,
      VSV-liposome fusion products included both viral proteins and lipids from
      liposomes, and were confirmed to be fusion products, but not adsorptive products,
      by the resonance energy transfer fusion assay. To evaluate whether these
      particles can efficiently introduce their internal contents into the cytoplasm of
      mammalian cells, we examined the delivery of fragment A of diphtheria toxin (DTA)
      by VSV-liposomes into the cytoplasm of FL cells. We found that VSV-liposomes
      encapsulating DTA were highly cytotoxic to the cells, while empty VSV-liposomes
      and plain liposomes encapsulating DTA were not, suggesting that VSV-liposomes
      delivered DTA into cytoplasm. Consistent with this, the cells cultured with
      plasmid DNA entrapped in VSV-liposomes and coding for firefly luciferase showed
      significant luciferase expression, whereas cells culture with plasmid DNA in
      plain liposomes and plasmid DNA-cationic liposomes complex did not. Thus, VSV
      liposomes function as a simple and efficient nonviral vector for the delivery of
      DNA.

PMID- 10925128
TI  - Polymer coating of liposomes with a modified polyvinyl alcohol and their systemic
      circulation and RES uptake in rats.
AB  - The objective of this study was to evaluate the in vivo characteristics of
      liposomes coated with a polyvinyl alcohol having a long alkyl chain at the end of
      the molecule (PVA-R) as an injectable drug carrier for passive targeting of
      drugs. A fluorescence marker, cholesteryl-anthracene-9-carboxylate, was
      incorporated into the liposomes to detect their concentration in the plasma and
      organs. The small unilamellar liposomes (100 nm in diameter) with various lipid
      compositions, such as the different cholesterol contents or the different
      charges, were prepared by the hydration method followed by sonication and coated
      with PVA or PVA-R by just mixing the resultant liposomal suspensions with the
      polymer solutions. The circulation and distribution of the liposomes were tested
      with their intravenous administration in rats. The PVA-R-coated liposomes showed
      significantly higher circulation compared to that of non-coated ones in any
      liposomal formulation tested. The prolonged circulation of PVA-R-coated liposomes
      was attributed to their fewer uptake in liver and spleen. The extent in
      improvement in the in vivo characteristics were well interpreted by the
      hydrophobicity of liposomes and their coating amount of PVA-R. It was also
      demonstrated that the liposomes having a positive and a negative charge, which
      showed the completely different circulating profiles, showed almost the same
      profile by coating with PVA-R. When the liposomes were coated with PVA the
      improvement in blood circulation was much less in any cases, although coating
      layer of PVA was detected. These results confirm that not only the hydrophilic
      property but the sterically stabilizing effect of the coating layer is important
      to prolong the circulation of the particulate drug carriers with less RES uptake,
      and the PVA-R having a hydrophobic moiety at the end of the molecule of PVA is a
      suitable material for the coating of liposomes.

PMID- 10925129
TI  - Scintigraphic evaluation in rabbits of nasal drug delivery systems based on
      carbopol 971p((R)) and carboxymethylcellulose.
AB  - The residence time of apomorphine mucoadhesive preparations incorporating 99mTc
      labeled colloidal albumin in rabbit nasal cavity was evaluated by gamma
      scintigraphy. This technique was used to compare the nasal clearance of
      preparations based either on Carbopol 971P((R)) or lactose (control), each with
      and without apomorphine, or carboxymethylcellulose with apomorphine. The planar 1
      min images showed an excipient-dependent progressive migration of radioactivity
      with time from the nasal cavity to the stomach and intestine. Thirty minutes post
      insufflation, the percentages of the formulations cleared from the nasal cavity
      were 47% for lactose, 26% for lactose/apomorphine, 10% for Carbopol 971P((R)),
      and 3% for both Carbopol 971P((R))/apomorphine and
      carboxymethylcellulose/apomorphine. Three hours post insufflation, the
      percentages of the formulations cleared from the nasal cavity were 70% for
      lactose, 58% for lactose/apomorphine, 24% for Carbopol 971P((R)), 12% for
      Carbopol 971P((R))/apomorphine, and 27% for carboxymethylcellulose/apomorphine.
      Apomorphine inhibited nasal mucociliary clearance since migration of the
      radioactivity administered with apomorphine containing preparations was in all
      cases slower than that of the corresponding powder without apomorphine. The peak
      plasma concentration of apomorphine was attained while all the formulations were
      still within the nasal cavity. The use of mucoadhesive polymers such as Carbopol
      971P((R)) or carboxymethylcellulose in nasal dosage forms increases their
      residence time within the nasal cavity and provides the opportunity for sustained
      nasal drug delivery.

PMID- 10925130
TI  - Studies on applicability of press-coated tablets using hydroxypropylcellulose
      (HPC) in the outer shell for timed-release preparations.
AB  - Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet
      and coated with hydroxypropylcellulose (HPC) as the outer shell, were examined
      for applicability as timed-release tablets with a predetermined lag time and
      subsequent rapid drug release phase. Various types of press-coated tablets were
      prepared using a rotary tabletting machine and their DIL dissolution behavior was
      evaluated by the JP paddle method. The results indicated that tablets with the
      timed-release function could be prepared, and that the lag times were prolonged
      as the viscosity of HPC and the amount of the outer shell were increased. The lag
      times could be controlled widely by the above method, however, the compression
      load had little effect. Two different kinds of timed-release press-coated tablets
      that showed lag times of 3 and 6 h in the in vitro test (denoted PCT(L3) and
      PCT(L6), respectively) were administered to beagle dogs. DIL was first detected
      in the plasma more than 3 h after administration, and both tablets showed timed
      release. The lag times showed a good agreement between the in vivo and in vitro
      tests in PCT(L3). However, the in vivo lag times were about 4 h in PCT(L6) and
      were much shorter than the in vitro lag time. The dissolution test was performed
      at different paddle rotation speeds, and good agreement was obtained between the
      in vivo and in vitro lag times at 150 rpm. This suggested that the effects of
      gastrointestinal peristalsis and contraction should also be taken into
      consideration for the further development of drug delivery systems.

PMID- 10925131
TI  - Design of fusogenic liposomes using a poly(ethylene glycol) derivative having
      amino groups.
AB  - As a novel fusogenic liposome, we designed liposomes modified with poly(glycidol)
      having beta-alanine residues, which is a poly(ethylene glycol) derivative with
      positively charged groups. The polymer-modified liposomes of egg yolk
      phosphatidylcholine (EYPC) and dioleoylphosphatidylethanolamine (DOPE) were
      prepared by reverse phase evaporation. Fusion of the polymer-modified liposomes
      with anionic liposomes consisting of phosphatidic acid and DOPE was investigated.
      Fusion ability of the polymer-modified liposomes increased with increasing amount
      of the polymer fixed on the liposome. Also, inclusion of DOPE was necessary for
      the generation of the fusion ability of the polymer-modified liposomes. CV1 cells
      treated with the polymer-modified DOPE/EYPC liposomes containing calcein
      displayed diffuse fluorescence, suggesting that calcein was introduced into the
      cytoplasm. In contrast, only punctual fluorescence was observed in the cells
      treated with the polymer-modified EYPC liposomes containing calcein, indicating
      that calcein remained in the endosome and/or lysosome. In addition, COS1 cells
      were transfected efficiently by treatment with the polymer-modified EYPC/DOPE
      liposomes containing pSV2cat plasmid, whereas the transfection was not induced by
      treatment with the polymer-modified EYPC liposomes. Close correlation between
      fusion ability of the polymer-modified liposomes and their ability to deliver
      their contents to the cytoplasm implies that membrane fusion plays an important
      role in the liposome-mediated cytoplasmic delivery.

PMID- 10925133
TI  - Ultrasound-facilitated transport of silver chloride (AgCl) particles in fish
      skin.
AB  - Electron-dense nano-particles in aqueous suspension were administered by
      immersion into the epidermis of fish using ultrasound in the therapeutic range.
      Enhanced permeability of the tissues to the particles was achieved by acoustic
      cavitation, which induced a controlled level of necrosis in the outer cell
      layers, and by non-cavitational exposures, which widened intercellular spaces of
      non-necrosed tissue in deeper regions of the epidermis. Both particle
      concentration and penetration depth were quantified using transmission electron
      microscopy. While cavitation-induced perforation was necessary for particles to
      penetrate into the tissues, non-cavitational exposures during immersions
      increased the particle flux towards the skin surface, as well as the diffusion
      rate of the particles within the epidermis and their depth of penetration. The
      technique described above may potentially be applied for non-stressful, mass
      administration of substances into aquatic animals, as well as the relatively new
      field of ultrasound-facilitated delivery in moist epithelial tissues in humans.

PMID- 10925132
TI  - Liposomes as carriers for DNA-PNA hybrids.
AB  - Peptide nucleic acids (PNAs) are DNA mimics composed of N-(2-aminoethyl)glycine
      units. This structure gives to PNAs (a) resistance to DNases and proteinases, (b)
      capacity to hybridize with high affinity to complementary sequences of single
      stranded RNA and DNA, and (c) capacity to form highly stable (PNA)(2)-RNA
      triplexes with RNA targets. Furthermore, DNA-PNA hybrid molecules are capable to
      reversibly interact with DNA-binding proteins, being therefore of interest for
      studies on regulation of gene expression by the decoy approach. The major
      conclusion of this paper is that cationic liposomes are able to efficiently
      complexate DNA-PNA hybrid molecules and mediate their binding to target cells.
      Our results are of some interest, since, unlike commonly used nucleic acids
      analogs, PNA oligomers are not taken up spontaneously into the cells. In
      addition, they are not suitable for an efficient delivery with commonly used
      liposomal formulations. Transfection of PNA-DNA hybrid molecules to in vitro
      cultured cells could be of great interest to determine the applications of these
      new reagents to experimental alteration of gene expression.

PMID- 10925134
TI  - Long-term sustained release of ganciclovir from biodegradable scleral implant for
      the treatment of cytomegalovirus retinitis.
AB  - The previous scleral implant composed of poly(D, L-lactide-co-glycolide) with
      ganciclovir (GCV) had some disadvantages such as the second burst in the late
      phase of release. In this study, the GCV release rate from scleral implants was
      modified by blending poly(D,L-lactide) (PLA) of two different molecular weights.
      The scleral implants were prepared by blending PLA-70000 (molecular weight:
      70000) and PLA-5000 (molecular weight: 5000) or PLA-130000 (molecular weight:
      130000) and PLA-5000 at weight ratios of 100/0, 95/5, 90/10, 80/20, and 0/100. In
      vitro release tests were performed in 0.1 M phosphate-buffered solution (pH 7.4)
      at 37 degrees C. An increase in the blended amount of PLA-5000 clearly
      accelerated the GCV release and the onset of the second burst in the late phase
      of release tended to delay. The two implants both prepared at a blend ratio of
      80/20 successfully prevented the second burst and the GCV release profiles
      followed the pseudozero-order kinetics after the initial burst as resulting from
      a diffusional mechanism following Higuchi's equation. Duration of the sustained
      GCV release could be controlled by changing the blending ratio of high and low
      molecular weight PLA. The 25% GCV-loaded scleral implants composed of PLA-70000
      and PLA-5000 with a blending ratio of 80/20 were implanted in pigmented rabbit
      eyes. The GCV concentrations in the vitreous after implantation of PLA-70000/PLA
      5000 scleral implant with a blending ratio of 80/20 were maintained in the range
      of effective level for 6 months without a significant burst. Our results suggest
      that the blended implants are promising for the intraocular controlled drug
      delivery over a period of several months to one year to treat cytomegalovirus
      retinitis.

PMID- 10925135
TI  - Evaluation of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)
      (PEO-PPO-PEO) gels as a release vehicle for percutaneous fentanyl.
AB  - The primary objective of this study was to investigate the feasibility of PEO-PPO
      PEO copolymer gel as a release vehicle for percutaneous administration of
      fentanyl in vitro and in vivo. A cellulose membrane and nude mouse skin with
      series concentrations of PEO-PPO-PEO block copolymers were used to examine the
      sustained-release pattern and permeation of fentanyl. The in vivo percutaneous
      absorption was examined using rabbits to evaluate the preliminary
      pharmacokinetics of fentanyl with 46% PEO-PPO-PEO copolymer formulation patches.
      The micelle formation ability of this block copolymer and the penetration ability
      of PEO-PPO-PEO copolymer over time were also studied by pyrene fluorescence probe
      methods and the dynamic light scattering test. At a concentration of 46% at 37
      degrees C, PEO-PPO-PEO copolymers formed a gel and showed a pseudo-zero-order
      sustained-release profile. With increasing concentration of copolymer in the
      cellulose membrane transport, the apparent release flux of fentanyl (200
      microgram/ml) decreased to 1. 09+/-0.19 microgram cm(-2) h(-1). Assessment of the
      effect of the copolymer on nude mouse skin also showed a decrease in the apparent
      permeability coefficient [(P(H(2)O))=2.24+/-0.47x10(-6) cm s(-1) vs. (P(46% block
      copolymer))=0.93+/-0.23x10(-7) cm s(-1)]. The preliminary pharmacokinetics of the
      fentanyl patch was shown to be in steady state within 24 h, and this was
      maintained for at least 72 h with an elimination half-life (t(1/2)) of 10.5+/-3.4
      h. A fluorescence experiment showed polymeric micelle formation of PEO-PPO-PEO
      copolymers at 0.1% (w/w) within 50 nm micelle size and the PEO-PPO-PEO copolymers
      were able to penetrate nude mouse skin within 24 h. Thus, it appears that
      fentanyl preparations based on PEO-PPO-PEO copolymer gel might be practical for
      percutaneous delivery.

PMID- 10925136
TI  - Investigation of the role of macrophages on the cytotoxicity of doxorubicin and
      doxorubicin-loaded nanoparticles on M5076 cells in vitro.
AB  - Doxorubicin-loaded PACA nanoparticles have been shown to be more efficient than
      free drug in mice bearing hepatic metastasis of the M5076 tumour. Due to the high
      phagocytic activity of Kupffer cells in the liver, it may be that these cells
      played a role of drug reservoir after nanoparticle phagocytosis. Therefore, the
      objective of this study was to assess the role of macrophages in mediating the
      cytotoxicity of doxorubicin-loaded nanoparticles on M5076 cells. The growth
      inhibition of tumour cells was evaluated in two ways: firstly, the cells were
      incubated in a coculture system consisting of special wells with two compartments
      separated by a porous membrane. M5076 cells were seeded into the lower
      compartment and the macrophages J774.A1 were introduced into the upper part. The
      macrophages were activated or not by IFN-gamma. The drug preparations were added
      only in the macrophage insert. Secondly, growth inhibition was also assessed in
      the conventional way, i.e. in direct contact with the tumour cells to serve as a
      reference. After direct contact, free doxorubicin (Dox) and doxorubicin-loaded
      nanoparticles (NP-Dox) had the same efficacy against M5076 cell growth. The
      coculture experiments led to a 5-fold increase in the IC(50) for both Dox and NP
      Dox. The activation of macrophages by IFN-gamma in coculture significantly
      decreased the IC(50) values. In conclusion, after phagocytosis of doxorubicin
      loaded nanoparticles, J774.A1 cells were able to release active drug, allowing it
      to exert its cytotoxicity against M5076 cells. Drug efficacy was potentiated by
      the activation of macrophages releasing cytotoxic factors such as NO, which
      resulted in increased tumour cell death. Thereby, the coculture system permitted
      us to investigate the macrophage-mediated cytotoxicity of colloidal carriers
      loaded with an anticancer drug, which is of great interest when further i.v.
      administration is envisaged.

PMID- 10925137
TI  - Oral bioavailability of a poorly water soluble HIV-1 protease inhibitor
      incorporated into pH-sensitive particles: effect of the particle size and
      nutritional state.
AB  - The new chemical entity CGP 70726, a very poorly water-soluble HIV-1 protease
      inhibitor, was incorporated into pH-sensitive nanoparticles and microparticles
      made of the poly(methacrylic acid-co-ethylacrylate) copolymer Eudragit((R)) L100
      55. The particles were characterized in terms of morphology, size distribution,
      drug loading, production yield and dispersion state of the drug inside the
      polymeric matrices. Aqueous dispersions of the particles were administered orally
      to Beagle dogs against a suspension of free drug (control formulation) all at a
      dose of 100 mg/kg. Oral administration was conducted in the absence and presence
      of food. Plasma concentrations and pharmacokinetic parameters were determined
      within 8 h post-dose. While no measurable absorption of the drug resulted after
      administration of the control formulation, substantial systemic exposure to the
      compound was obtained with both kinds of pH-sensitive formulations. The selective
      release of CGP 70726 in a highly dispersed/amorphous state and creation of high
      concentrations close to its absorption site was thought to account for this
      positive result. The largest areas under the plasma concentration-time curve
      (AUC) were obtained in the fasted state, with slightly better performance of the
      microparticles over the nanoparticles, in both nutritional states (7.8+/-1.5
      versus 5.8+/-0. 8 micromol.h/l in the fasted state; 4.4+/-1.4 versus 2.00+/-0.5
      micromol.h/l in the fed state). With these results, the potential of pH-sensitive
      particles for the oral delivery of HIV-1 protease inhibitors with low water
      solubility was confirmed.

PMID- 10925139
TI  - Nucleus-specific expression of ionotropic glutamate receptor subunit mRNAs and
      binding sites in primate thalamus.
AB  - Thalamic afferents and efferents utilize glutamate as their primary
      neurotransmitter. There are four families of glutamate receptors that can
      transduce this activity, as well as regulate glutamate release from thalamic
      relay neurons. The three ionotropic subtypes are of particular importance,
      because subunit composition confers variability in functional properties of each
      subtype. We have quantified the expression of NMDA, AMPA and kainate receptors in
      the thalamus of the macaque using receptor autoradiography and in situ
      hybridization. NMDA receptors are multimeric associations of NR1 and NR2A-NR2D
      subunits that form ligand-gated ion channels. Particular subunits are associated
      with modulatory binding sites that affect receptor activity. NR1 was the most
      abundant subunit mRNA; NR2A, NR2B, and NR2D subunit mRNAs were also present, but
      were expressed in nucleus-specific patterns. Very high levels of [3H]ifenprodil
      binding to the polyamine site of the NMDA complex were detected in a fairly
      homogeneous distribution. Binding of the ion channel ligand [3H]MK-801 was also
      abundant, and limbic nuclei expressed higher levels than motor nuclei or the
      reticular nucleus. [3H]CGP39653 binding to the glutamate site of the NMDA
      receptor was the least abundant of the NMDA receptor binding sites. There was
      variability in the stoichiometric relationships of binding sites across nuclei,
      suggesting that there is heterogeneity in the pharmacological properties of NMDA
      receptors expressed in the thalamus. AMPA and kainate are also multimeric
      associations of specific subunits that form ligand-gated ion channels. These
      subunits are encoded by specific genes: gluR1-gluR4 for AMPA receptors, and gluR5
      gluR7 and KA1-KA2 for kainate receptors. GluR4 and gluR6 mRNAs were, respectively
      the most abundant of the AMPA and kainate receptor subunit transcripts. Both AMPA
      and kainate receptor subunit transcripts were expressed in a nucleus-specific
      pattern. The binding of [3H]kainate was higher than that of [3H]AMPA throughout
      the thalamus, but AMPA subunit mRNA levels were three to five orders of magnitude
      higher than those encoding the kainate receptor subunits. The mismatch between
      the levels of expression of kainate receptor subunit transcripts and binding
      sites is suggestive of a presynaptic localization of kainate receptors on
      thalamic afferents. These results suggest that ionotropic glutamate receptors are
      heterogeneously expressed in the thalamus of the primate, and that their
      differential expression is both subunit- and nucleus-specific.

PMID- 10925140
TI  - Post-transcriptional inhibition of lipopolysaccharide-induced expression of
      inducible nitric oxide synthase by Go6976 in murine microglia.
AB  - Glia in the brain respond to various toxins with an increased expression of
      inducible nitric oxide synthase (iNOS) and an increased production of nitric
      oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of
      iNOS was down-regulated post-transcriptionally through the destabilization of
      iNOS mRNA by the indolocarbazole compound, Go6976, in murine microglia. This
      Go6976 effect is specific for iNOS since tumor necrosis factor alpha was
      unaffected by the compound. Interestingly, the post-transcriptional effects
      ascribed to Go6976 were not observed with other inhibitors of protein kinase A, C
      (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect
      the iNOS/NO system at the transcriptional level. In the past, Go6976 has been
      reported to be a rather specific inhibitor of PKC in vitro. Results from our
      experiments, through prolonged treatment with phorbol esters and with the various
      PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest
      that the Go6976-mediated post-transcriptional regulation of iNOS gene expression
      and NO production in microglia is not mediated through its reputed effects on PKC
      activity. Since the effects of various neurotoxins and certain neurodegenerative
      diseases may be manifested through alterations in the iNOS/NO system, post
      transcriptional control of this system may represent a novel strategy for
      therapeutic intervention.

PMID- 10925141
TI  - The indolocarbazole Go6976 protects neurons from lipopolysaccharide/interferon
      gamma-induced cytotoxicity in murine neuron/glia co-cultures.
AB  - The expression of inducible nitric oxide synthase (iNOS) and the production of
      nitric oxide (NO) after exposure to endotoxins has been implicated in immune
      mediated neurotoxicity. The indolocarbazole compound Go6976, which has been
      described as a selective protein kinase C (PKC) inhibitor in vitro, rescued
      neurons from lipopolysaccharide/interferon-gamma (LPS/IFNgamma)- or interleukin
      1alpha/tumor necrosis alpha/IFNgamma (IL-1alpha/TNFalpha/IFNgamma)-induced
      cytotoxicity in murine primary neuron-glia co-cultures. Other compounds known to
      inhibit PKC, Ro31-8220, GF109203X, Go7874, H7, staurosporine and H89, failed to
      rescue neurons from the LPS/IFNgamma-induced cytotoxicity. These results suggest
      that the neuroprotection by Go6976 from the LPS/IFNgamma-induced neuronal cell
      death is not mediated through its reputed effects on PKC activity. The
      neuroprotection paralleled the inhibition of iNOS gene expression and NO
      production. However, further analyses correlating NO production with the extent
      of neurotoxicity suggested that additional mechanism(s) besides the inhibition of
      the iNOS/NO system may be responsible for the neuroprotective effects of Go6976.
      An understanding of the mechanism underlying the neuroprotective effect of Go6976
      may provide key insights into potential interventions for immune-mediated
      neurodegenerative diseases.

PMID- 10925142
TI  - Up-regulation of tyrosine hydroxylase mRNA in a sub-population of A10 dopamine
      neurons in Parkinson's disease.
AB  - Neuronal injury has been consistently found in A10 midbrain dopamine neurons in
      Parkinson's disease (PD). To assess changes in neurotransmitter-related gene
      transcription, in these neurons in PD, tyrosine hydroxylase (TH) mRNA expression
      was examined in the ventral tegmental area (VTA) of seven PD cases and seven
      control subjects, using in situ hybridization histochemistry (ISHH). In controls,
      TH mRNA expression was found in both melanised and non-melanised neurons in the
      VTA. Neither population expressed dopamine beta-hydroxylase (DBH). Of the
      melanised neurons, 99% were TH mRNA positive. The level of the TH mRNA signal
      (expressed as grain density per cell) was similar in the two populations
      (melanised: 0.129+/-0.004 (mean+/-S.E.M.), n=142 vs. non-melanised: 0.138+/
      0.006, n=89, P>0.05, Student's t-Test). In PD cases there was no significant
      change in TH mRNA expression in melanised neurons (0.138+/-0.003, n=196), and the
      proportion of positively labeled melanised neurons was 98%. However, non
      melanised neurons showed significantly higher TH mRNA (0.163+/-0.006, n=87) than
      non-melanised neurons in control subjects (P<0.005) and melanised neurons in the
      PD cases (P<0.0005). This up-regulation of TH mRNA expression in non-melanised
      neurons may suggest the existence of a compensatory mechanism at presynaptic
      level.

PMID- 10925143
TI  - Mutation of tyrosine 318 (Y318F) in the delta-opioid receptor attenuates tyrosine
      phosphorylation, agonist-dependent receptor internalization, and mitogen
      activated protein kinase activation.
AB  - Opioid receptors are known for their ability to activate diverse second messenger
      systems. Previously, we showed that selective delta-opioid agonists were able to
      induce the rapid tyrosine phosphorylation of delta-opioid receptors (delta-ORs)
      through Src. Src-dependent tyrosine phosphorylation of delta-ORs appears to be
      important for activation of the mitogen-activated protein kinase cascade and for
      receptor sequestration into clathrin-coated endosomes, as the Src antagonist,
      PP1, inhibited both. In an attempt to clarify the role of tyrosine
      phosphorylation in delta-OR signalling and regulation, we constructed a mutant
      receptor in which the tyrosine located in the conserved NPXXY motif of the C
      terminus was replaced by a phenylalanine (Y318F-delta-OR). Mutation of Y318
      resulted in a receptor that was comparable to the wild type in its expression
      level in HEK-293 cells and in its affinity for opioid ligands. Both receptors
      showed effective coupling to G proteins and were capable of inhibiting forskolin
      stimulated cAMP accumulation with similar potencies. However, the mutant receptor
      was able to stimulate (35)S-GTPgammaS binding with a lower EC(50) than the wild
      type receptor. The stimulation of tyrosine phosphorylation in delta-ORs by [D
      Thr(2)]-Leu-enkephalin-Thr (DTLET) was significantly less in cells expressing the
      Y318F-delta-OR than in cells expressing the wild type. In addition, both rapid
      receptor internalization and down-regulation were markedly attenuated in the
      mutant. Finally, the mutant receptor was unable to induce a robust activation of
      the MAPK pathway, suggesting that tyrosine phosphorylation of the delta-OR
      protein is important for this signalling pathway. These findings implicate
      tyrosine phosphorylation of Y318 in receptor signalling and agonist-mediated
      regulation.

PMID- 10925144
TI  - Pituitary adelylate cyclase-activating peptide is an activator of vasoactive
      intestinal polypeptide gene transcription in human neuroblastoma cells.
AB  - In many ganglia, the neuropeptide pituitary adenylate cyclase-activating peptide
      (PACAP) innervates nerve cell bodies containing the homologous neuropeptide
      vasoactive intestinal polypeptide (VIP). We therefore investigated whether PACAP
      affected the VIP gene expression and elucidated the molecular mechanisms using
      the human neuroblastoma cell line NB-1. A concentration dependent induction of
      the VIP mRNA level was found upon PACAP stimulation. Five nM PACAP mediated
      transient elevation of the VIP mRNA being evident after 2 h, the maximal 65-fold
      induction was reached after 6-8 h and hereafter the level decreased rapidly. In
      cell extracts, the concentration of immunoreactive VIP was elevated four-fold
      upon PACAP stimulation for 8 h, and it remained elevated during the next 40 h. In
      conditioned medium, a stable 20-fold VIP increase was seen after 8-24 h.
      Experiments with the translational inhibitor cycloheximide showed a direct effect
      of PACAP on the VIP mRNA level, and nuclear run-on assays revealed a three- to
      four-fold enhancement of the VIP gene transcription rate after PACAP stimulation.
      The VIP mRNA induction was abolished by transcriptional inhibition with the
      actinomycin D, and PACAP did not seem to mediate any changes in the VIP mRNA half
      life. However, the VIP mRNA level seemed very stable during the transcriptional
      cessation. Reporter gene constructs were used to evaluate involvement of the VIP
      CRE site in the PACAP mediated induction of the VIP gene transcription. Mutation
      of the CRE site did not abolish the induction suggesting it to be of minor if any
      importance for the induction. In conclusion, the PACAP mediated induction of the
      VIP gene expression suggests that PACAP released from nerve terminals could
      influence the function of VIP'ergic neurons in target tissues.

PMID- 10925145
TI  - alpha-actinin-2 in rat striatum: localization and interaction with NMDA glutamate
      receptor subunits.
AB  - Alpha-actinin (alpha-actinin-2) is a protein which links the NR1 and NR2B
      subunits of N-methyl-D-aspartate (NMDA) glutamate receptors to the actin
      cytoskeleton. Because of the importance of NMDA receptors in modulating the
      function of the striatum, we have examined the localization of alpha-actinin-2
      protein and mRNA in striatal neurons, and its biochemical interaction with NMDA
      receptor subunits present in the rat striatum. Using an alpha-actinin-2-specific
      antibody, we found intense immunoreactivity in the striatal neuropil and within
      striatal neurons that also expressed parvalbumin, calretinin and calbindin.
      Conversely, alpha-actinin-2 immunoreactivity was not detected in neurons
      expressing choline acetyltransferase and neuronal nitric oxide synthase. Dual
      label in situ hybridization revealed that the highest expression of alpha-actinin
      2 mRNA is in substance P-containing striatal projection neurons. The alpha
      actinin-2 mRNA is also present in enkephalinergic projection neurons and
      interneurons expressing parvalbumin, choline acetyl transferase and the 67-kDa
      isoform of glutamic acid decarboxylase, but was not detected in somatostatin
      expressing interneurons. Immunoprecipitation of membrane protein extracts showed
      that alpha-actinin-2 is present in heteromeric complexes of NMDA subunits, but is
      not associated with AMPA receptors in the striatum. A subunit-specific anti-NR1
      antibody co-precipitated major fractions of NR2A and NR2B subunits, but only a
      minor fraction of striatal alpha-actinin-2. Conversely, alpha-actinin-2 antibody
      immunoprecipitated only modest fractions of striatal NR1, NR2A and NR2B subunits.
      These data demonstrate that alpha-actinin-2 is a very abundant striatal protein,
      but exhibits cellular specificity in its expression, with very high levels in
      substance-P-containing projection neurons, and very low levels in somatostatin
      and neuronal nitric oxide synthase interneurons. Despite the high expression of
      this protein in the striatum, only a minority of NMDA receptors are linked to
      alpha-actinin-2. This interaction may identify a subset of receptors with
      distinct anatomical and functional properties.

PMID- 10925146
TI  - Differential changes of bax, caspase-3 and p21 mRNA expression after transient
      focal brain ischemia in the rat.
AB  - Recent studies of transient focal ischemia have focused interest on apoptotic
      mechanisms of neuronal cell death involving constitutive pro-apoptotic proteins.
      The finding of specific patterns of novel gene expression might indicate the
      activation of pro-apoptotic genes in previously ischemic areas. Thus, we
      investigated gene expression for the pro-apoptotic regulators, Bax and caspase-3,
      after transient focal brain ischemia, together with the p53-regulated cell cycle
      inhibitor, p21/WAF1/CIP1. Reversible occlusion of the middle cerebral artery for
      2 h was carried out in halothane-anesthetized rats using the poly-L-lysine coated
      filament method. In situ hybridization was performed at 0, 1, 3, 6 h and 1, 3 and
      7 d of recirculation and in sham controls. Radioactive antisense probes served
      for detection of bax, p21 and caspase-3 mRNAs on brain sections, and quantitative
      film autoradiography was combined with image-averaging techniques. Bax mRNA
      tended to decline after focal brain ischemia within 1 d. p21 mRNA was upregulated
      with a perifocal pattern at 3 h and 1 d after ischemia whereas the ischemic
      regions themselves failed to show significant upregulation. Caspase-3 mRNA was
      elevated in the resistant dorsomedial cortex at 1 d. A pro-apoptotic pattern of
      novel gene expression, involving Bax and caspase-3, was not observed after
      transient focal brain ischemia. Rather, the perifocal expression of p21 and
      caspase-3 mRNAs observed at 1 d after ischemia points to reactive changes in
      resistant brain areas.

PMID- 10925148
TI  - Perinatal asphyxia induces region-specific long-term changes in mRNA levels of
      tyrosine hydroxylase and dopamine D(1) and D(2) receptors in rat brain.
AB  - To study the effects of neonatal asphyxia on gene expression of the dopaminergic
      systems, we determined quantitatively the mRNA levels of tyrosine hydroxylase,
      dopamine transporter, dopamine D(1) and D(2) receptors in substantia
      nigra/ventral tegmental area, striatum and limbic area. The mRNA levels were
      determined at one and 4 weeks after asphyxia by a quantitative reverse
      transcription polymerase chain reaction method. Spontaneously and Caesarean
      section born rats showed similar mRNA levels with the exception of an increase of
      tyrosine hydroxylase mRNA levels in the limbic area of 4-week-old animals. Five
      min of asphyxia did not change the mRNA levels in any region compared to that in
      the spontaneously born rats. Fifteen and twenty min of asphyxia induced region
      specific alterations in mRNA levels. In SN/VTA an increase of tyrosine
      hydroxylase mRNA levels in the 1-week-old rats and in striatum an increase of
      D(1) and D(2) dopamine receptor mRNA levels in the 4-week-old rats were observed.
      Fifteen min of asphyxia induced a selective increase of D(1) and D(2) dopamine
      receptor mRNA levels in the limbic area of 4-week-old rats. These observations
      indicate that neonatal asphyxia triggers a cascade of gene expressions for
      tyrosine hydroxylase and D(1) and D(2) dopamine receptors. In 1-week-old rats,
      the gene expression of tyrosine hydroxylase increased in the cell body region
      substantia nigra/ventral tegmental area. This change may increase the D(1) and
      D(2) dopamine receptor expression in the target regions striatum and limbic area
      during further development.

PMID- 10925147
TI  - Acute stress increases neuropeptide Y mRNA within the arcuate nucleus and hilus
      of the dentate gyrus.
AB  - The effects acute restraint stress on neuropeptide Y (NPY) mRNA expression were
      determined within the dentate gyrus and arcuate nucleus, where the effects of
      adrenal steroid action were previously reported. Adult male rats were exposed to
      1 h of restraint stress and then sacrificed immediately, 6 h, or 24 h later.
      Controls were undisturbed. Stress increased NPY mRNA levels in both the arcuate
      nucleus and in the hilar region of the hippocampus with different time courses.
      NPY mRNA increased in the arcuate at 24 h, but not earlier, as determined by film
      autoradiography. Single cell grain analysis was performed in the dentate gyrus
      hilus because the NPY mRNA was heterogeneously distributed and revealed that the
      number of cells expressing NPY mRNA increased 6 h after stress, returning to
      control levels within 24 h. These results fit with previously reported effects of
      adrenal steroids modulating arcuate nucleus NPY expression through the adrenal
      steroid Type II receptors. In the hilus where adrenal steroid Type I receptors
      have been reported to suppress NPY mRNA levels, the effect of stress is in the
      opposite direction to that of adrenal steroid action and a more complex
      regulation of NPY expression is indicated.

PMID- 10925149
TI  - Down syndrome cell adhesion molecule DSCAM mediates homophilic intercellular
      adhesion.
AB  - Down Syndrome (DS) caused by trisomy 21 is the most common birth defect
      associated with mental retardation. Recently, a novel gene named, DSCAM, has been
      identified in the DS critical region. DSCAM is predicted to be a transmembrane
      protein with a very high structural and sequence homology to Ig superfamily of
      cell adhesion molecules and is expressed in the developing nervous system with
      the highest level in fetal brain. Diverse glycoproteins of cell surfaces and
      extracellular matrices operationally termed as 'adhesion molecule' are important
      in the specification of cell interactions during development, maintenance and
      regeneration of the nervous system. To understand the cellular function of DSCAM
      protein, we transfected human DSCAM cDNA into mouse fibroblast L cells and
      analysed its expression. On Western blot analysis, antibodies raised against
      recombinant DSCAM-Ig3 recognized a 198 kDa protein band in the membrane fraction
      of DSCAM transfected L cells. Stable transformants expressing DSCAM showed
      uniform surface expression. DSCAM-expressing transfectants exhibited enhanced
      adhesive properties, aggregating with faster kinetics and forming aggregates in a
      homophilic manner. Divalent cations are not required for this cell aggregation.
      These results demonstrate that DSCAM is a cell adhesion molecule that can mediate
      cation-independent homophilic binding activity between DSCAM expressing cells.

PMID- 10925150
TI  - Transcriptional regulation of gene expression of sec6, a component of mammalian
      exocyst complex at the synapse.
AB  - Sec6, an essential component of the mammalian brain exocyst complex, is believed
      to function in synapse formation and synaptic plasticity. During neuronal
      development, the expression of the Sec6 gene correlates temporally with neurite
      outgrowth and synaptogenesis. To understand the mechanisms that regulate the Sec6
      gene expression, we have cloned and characterized the 5'-terminal region of the
      murine Sec6 gene. We have shown that the 5'-untranslated region of the murine
      Sec6 gene is encoded by two exons that are separated by a 1560-bp intron. Primer
      extension analysis demonstrates that Sec6 gene transcription is initiated from a
      unique site. The Sec6 promoter is embedded in a CpG island and lacks canonical
      TATA or CAAT boxes. Sequence analysis of the 5'-flanking region and the first
      intron reveals the presence of a number of binding sites for transcription
      factors AP-1, AP-2, AP-4, ATF, C/EBPbeta, GATA-1, Oct 1, SP1, STAT, and NRSF.
      Transfection experiments using Sec6-luciferase fusion genes demonstrate that the
      5'-flanking sequence functions as a strong promoter in neuronal but not in
      nonneuronal cells. Deletion analysis reveals the presence of a core promoter
      between nucleotide position -139 and +53, and two enhancer and four silencer
      elements within the 5'-flanking region and the first intron sequence. These
      results indicate that neuronal expression of the Sec6 gene involves a relatively
      specific core promoter and interplay between multiple positive and negative
      regulatory elements.

PMID- 10925151
TI  - Chronic DeltaFosB expression and increased AP-1 transcription factor binding are
      associated with the long term plasticity changes in epilepsy.
AB  - NMDA receptor activation during status epilepticus (SE) has previously been shown
      to be required for epileptogenesis as well as the persistent upregulation of
      serum response factor (SRF) in the in vivo pilocarpine model of epilepsy. SRF is
      established as a regulator of the FosB gene which expresses FosB and DeltaFosB
      components of the AP-1 transcription factor complex. Therefore we investigated
      whether DeltaFosB expression and AP-1 DNA binding were also persistently elevated
      in pilocarpine-treated rats which chronically displayed spontaneous seizures.
      Using hippocampal nuclear extracts, DeltaFosB expression and AP-1 DNA binding
      were significantly elevated for up to one year in the epileptic animals. The
      expression of other fos and jun proteins was not persistently altered in
      epilepsy. Neuronal upregulation of DeltaFosB was correlated with regions of the
      brain that were involved in seizure generation and propagation. The increase in
      AP-1 DNA binding was shown to be dependent on NMDA receptor activation during SE.
      Hippocampal DeltaFosB immunostaining was seen predominately in the neuronal
      nuclei as opposed to other cell types. The data indicate that recurrent seizures
      which persistently occur in this model were not responsible for the increased
      DeltaFosB expression. Chronic DeltaFosB expression in epilepsy may be playing a
      role in the altered expression of other genes in this model and may be involved
      in some of the neuronal plasticity changes associated with epileptogenesis.

PMID- 10925152
TI  - Transient increase of brain derived neurotrophic factor mRNA expression in
      substantia nigra reticulata after partial lesion of the nigrostriatal
      dopaminergic pathway.
AB  - By using non-isostopic in situ hybridization we have demonstrated a transient
      increase of BDNF mRNA in the lateral subregion of the substantia nigra pars
      reticulata 1 week after intrastriatal application of 6-OH-DA. These changes
      correlate with a partial reduction of dopamine (DA) content in the striatum but
      with a normal tyrosine hydroxylase immunoreactivity in substantia nigra pars
      compacta. Our data suggest that non-DA, BDNF expressing cells in substantia nigra
      pars reticulata may play a role in neuronal protection after partial lesions of
      the DA nigrostriatal pathway.

PMID- 10925153
TI  - IL-1beta induced changes in hypothalamic IL-1R1 and IL-1R2 mRNA expression in the
      rat.
AB  - Interleukin-1 receptor (IL-1R1 and IL-1R2) mRNA expression was detected within
      the rat hypothalamus, a primary site of IL-1 action, using RT-PCR. Levels of
      expression were unchanged by cardiac saline-perfusion. However,
      intracerebroventricular (i.c.v.) administration of IL-1beta caused changes in
      receptor mRNA expression in non-perfused animals that were profoundly different
      to those observed in their saline-perfused counterparts. This study demonstrates
      the importance of perfusing tissue to remove blood cells when determining changes
      in IL-1 receptor mRNA expression.

PMID- 10925154
TI  - Control of mu opioid receptor expression by modification of cDNA 5'- and 3'
      noncoding regions.
AB  - Removal of a 712 base pair (bp) sequence following the coding region of a human
      micro opioid receptor (hmuOR) cDNA unexpectedly increased expression of the
      receptor protein. A series of 3'-noncoding region deletion mutants revealed that
      at least three discrete regions following the stop codon influenced receptor
      expression levels. Deletion of the 205-bp 5'-noncoding region immediately
      preceding the Kozak sequence doubled receptor expression relative to wild type,
      and simultaneous deletion of 5'- and 3'-noncoding regions increased expression
      several fold. The hmuOR noncoding regions may participate in a regulatory
      mechanism that controls the number of cell surface receptors.

PMID- 10925155
TI  - Changes in 5-HT(7) serotonin receptor mRNA expression with aging in rat brain.
AB  - We examined 5-HT(7) receptor mRNA expression with in situ hybridization
      histochemistry in the brains of young (3 months), middle-aged (12 months) and old
      rats (24 months). In the ventral CA3 area of the hippocampus 5-HT(7) mRNA
      expression is reduced by approximately 30% between young and middle age without
      further decline between middle and old age. In other brain areas 5-HT(7) mRNA
      expression is unaffected by age.

PMID- 10925156
TI  - 10 kD mitochondrial matrix heat shock protein mRNA is induced following global
      brain ischemia in the rat.
AB  - Heat shock proteins (HSP's) are a family of highly conserved proteins whose
      expression is increased by stress. The expression of many HSP's is induced in
      neurons by ischemia; however, the response of the 10 kDa mitochondrial matrix HSP
      (HSP10) is less well characterized. To address this issue, asphyxial cardiac
      arrest was induced in 28 male Sprague-Dawley rats. Northern blot analysis
      revealed that hsp10 mRNA was increased 2.7-fold in asphyxiated rats compared to
      sham-operated controls. In situ hybridization demonstrated increased mRNA in the
      cortex, septal nuclei, hippocampus, thalamic nuclei, purkinje cell layer of the
      cerebellum, and isolated brainstem nuclei of asphyxiated rats. The increase of
      mRNA was most robust 8 h after the injury but remained increased for 72 h. These
      results show that hsp10 mRNA is increased following asphyxial cardiac arrest in
      rats and suggest that hsp10 could be another determinate of neuronal survival
      after ischemia.

PMID- 10925157
TI  - Effects of chronic ethanol administration on expression of BDNF and trkB mRNAs in
      rat hippocampus after experimental brain injury.
AB  - Previous evidence indicates that both chronic alcohol treatment and traumatic
      brain injury modulate expression of certain neurotrophins and neurotrophin
      receptors in cortical tissue. However, the combined effects of chronic alcohol
      and brain trauma on expression of neurotrophins and their receptors have not been
      investigated. In the present study, we examined the effects of 6 weeks of chronic
      ethanol administration on lateral fluid percussion (FP) brain injury-induced
      alterations in expression of mRNAs for the neurotrophin brain-derived
      neurotrophic factor (BDNF) and its high affinity receptor, trkB, in rat
      hippocampus. In both the control- (pair-fed isocaloric sucrose) diet and the
      chronic ethanol-diet groups, unilateral FP brain injury induced a bilateral
      increase in levels of both BDNF and trkB mRNAs in the dentate gyrus granule cell
      layer, and of BDNF mRNA in hippocampal region CA3. However, no significant
      differences in expression were found between the control-diet and ethanol-diet
      groups, in either the sham-injured or FP-injured animals. These findings suggest
      that 6 weeks of chronic ethanol administration does not alter the plasticity of
      hippocampal BDNF/trkB expression in response to experimental brain injury.

PMID- 10925158
TI  - Roles of Sox4 in central nervous system development.
AB  - The transcription factor-encoding gene, Sox4, is expressed in a wide range of
      tissues and has been shown to be functionally involved in heart, B-cell and
      reproductive system development. Sox4 shows a high degree of sequence homology
      with another group C Sox gene, Sox11, which is predominantly expressed in the
      CNS. Since the expression of Sox4 in the CNS has not been described we have
      carried out such a study. Sox4 and Sox11 expression increased simultaneously in
      the same early differentiating cells of the developing CNS except in the external
      granule layer of the cerebellum where Sox11 expression preceded that of Sox4. As
      development proceeded, their expression always appeared to relate to the
      maturational stage of the cell population, with Sox11 expression more transient
      than Sox4, except in the spinal cord where the reverse was true. Sox4 knock-out
      mice have been shown to die of a heart defect half way through gestation with no
      observable CNS phenotype. Our more detailed analysis showed no abnormality in the
      spatial restriction of expression of Sox2, Sox11, Mash1, neurogenin1 or
      neurogenin2, although the level of expression of Sox11 and Mash1 appeared a
      little different from the wild-type, implying that Sox4 might indeed have a
      functional role in CNS development. However, since Sox4 and Sox11 expression is
      so similar, we propose that Sox11 might compensate for the loss of Sox4 function
      in the CNS such that the phenotype is extremely mild in the Sox4 null mutant.

PMID- 10925160
TI  - Neuronal oxidative hypometabolism in the brainstem of the epaulette shark
      (Hemiscyllium ocellatum) in response to hypoxic pre-conditioning.
AB  - Reduced oxidative demand or neuronal hypometabolism is a neuroprotective strategy
      used by several anoxia and hypoxia-tolerant species. The epaulette shark,
      Hemiscyllium ocellatum inhabits shallow reef platforms that can become hypoxic.
      Hypoxic pre-conditioning (eight cycles of 0.34 mg O(2)/l for 120 min, 12 h apart)
      was used to determine whether a reduction in oxidative metabolism could be
      elicited in the epaulette shark brain. Hypoxic pre-conditioning resulted in a
      significant overall reduction in oxidative activity in coronal sections of the
      brainstem, but key nuclei displayed heterogeneous levels of oxidative metabolism.
      Motor nuclei had significantly lower levels of oxidative activity while sensory
      nuclei did not. The epaulette shark's ability to enter this state of
      hypometabolism in response to hypoxic pre-conditioning revealed a neuroprotective
      mechanism, which would not only reduce neuronal damage during hypoxic exposure
      but also minimise re-oxygenation injury.

PMID- 10925159
TI  - Two trans-acting rat-brain proteins, MARTA1 and MARTA2, interact specifically
      with the dendritic targeting element in MAP2 mRNAs.
AB  - Different isoforms of the microtubule-associated protein 2 (MAP2) are
      somatodendritic components of neurons that seem to regulate the stability of the
      dendritic cytoskeleton. MAP2 localization into dendrites appears to be a complex
      multicausal mechanism that involves the specific recruitment of MAP2 mRNAs into
      dendritic compartments. Recently, we have functionally characterized a 640
      nucleotide dendritic targeting element (DTE) in the 3' untranslated region (3'
      UTR) of MAP2 transcripts that mediates extrasomatic mRNA localization in primary
      neurons (Blichenberg et al. , 1999). In analogy to molecular mechanisms
      regulating cytoplasmic RNA translocation in other cell systems, we propose that,
      in vivo, the cis-acting MAP2-DTE interacts with specific protein factors present
      in neurons. To identify putative trans-acting DTE-binding proteins, we performed
      in vitro ultraviolet crosslinking assays. Using this experimental system, two 90
      kDa and 65-kDa MAP2-RNA trans-acting proteins, MARTA1 and MARTA2, were identified
      in rat-brain extracts. Both MARTAs bind with high affinity to the MAP2-DTE, but
      not to other investigated regions of MAP2 transcripts or the somatically
      restricted alpha-tubulin mRNA. Moreover, MARTA1 and MARTA2 do not bind
      significantly to other dendritically localized transcripts encoding vasopressin
      and arg3.1, nor to a dendritic trafficking element from the mRNA encoding the
      alpha-subunit of the Ca(2+)/calmodulin-dependent protein kinase II. Binding of
      MARTA1 and MARTA2 to the MAP2-DTE occurs with an affinity in the nanomolar range.
      Whereas MARTA1 is clearly detectable in crude lysates, cytosolic and ribosomal
      salt-wash fractions, and in nuclear extracts, MARTA2 is preferentially found in
      the ribosomal salt-wash preparation. Neither MARTA is restricted to rat brain,
      and both are present in a number of other rat tissues. Thus, both proteins may be
      involved in a variety of nuclear and cytoplasmic events that regulate RNA
      metabolism in different cell types.

PMID- 10925161
TI  - Successful generation of peripheral neuropathy with onion-bulb formation in the
      macrophage scavenger receptor classA knockout mouse treated with isoniazid.
AB  - We previously reported successful generation of many onion-bulbs (OBs) and
      formation of oxidized phosphatidylcholine after compression injury to the
      peripheral nerve of mice deficient of macrophage scavenger receptor classA (MSR
      A). In the present study, we employed chemical injury with isoniazid to the
      peripheral nerve of the MSR-A knockout mice to investigate the role of the MSR-A
      in toxic neuropathy. Peripheral neuropathy has not previously been generated with
      isoniazid in mice. In the present study, we also noted little histological change
      after isoniazid administration not only to control littermates but also to the
      A/J strain mice known to be slow acetylators. Surprisingly, however, we were
      successful in generating peripheral neuropathy with isoniazid in the MSR-A
      knockout mice. Histologically, the predominant feature was the presence of many
      thinly myelinated fibers with some OBs, which have not been observed in rats with
      isoniazid neuropathy. Deficiency of the MSR-A appears to have played an important
      role in generation of peripheral neuropathy with isoniazid in mice.

PMID- 10925162
TI  - Potassium channel openers prevent beta-amyloid toxicity in bovine vascular
      endothelial cells.
AB  - There is increasing evidence that the cerebrovasculture may be involved in the
      pathology of Alzheimer's disease. Here, we report that potassium channel openers
      (KCOs) inhibit dose and time dependent necrosis induced by beta-amyloid (Abeta)
      in cultured vascular endothelial cells. Cell proliferation rate was assayed by a
      colorimetric method. Abeta cytotoxicity and inhibition by the K(ATP) channel
      opener diazoxide and the K(Ca) channel opener NS1619 was correlated with changes
      in nitric oxide (NO) production. The protective effects were partly blocked by
      potassium channel blockers. Toxicity of Abeta and KCO protection was verified by
      histological examination of endothelial cells with scanning electron microscopy.
      eNOS levels in endothelial cells were not changed by any of the treatments. The
      results suggest that disruption of K(+) channels function may be a critical step
      in Abeta-induced cytotoxicity in endothelial cells by alteration of NO release.

PMID- 10925163
TI  - Improvement of presurgical patient evaluation by generation of functional
      magnetic resonance risk maps.
AB  - Recent functional magnetic resonance imaging (FMRI) replication studies show a
      high variability of active voxels within subjects and across runs - a potentially
      harmful situation for clinical applications. We tried to reduce these
      uncertainties inherent in current presurgical FMRI. For this, a new high quality
      head fixation device was used to detect reliably activated voxels over repeated
      measurements. In addition high correlation thresholds were applied to define the
      areas with highest probability of activation. The results show a focussing of
      such functional high risk areas to only a few voxels which localized close to
      intraoperative cortical stimulation. The generation of such FMRI risk maps may
      improve validity of clinical localization and facilitate the development of
      currently missing standards for maximized but still safe tumor resection.

PMID- 10925164
TI  - Ultrastructure and function of the amoeboid microglial cells in the
      periventricular white matter in postnatal rat brain following a hypoxic exposure.
AB  - The ameboid microglial cells (AMC), located in the periventricular white matter,
      were examined ultrastucturally in neonatal rats following a hypoxic exposure. For
      10 min to 1 day, following the hypoxic exposure, a large number of glial cells
      with nuclear chromatin condensation, undergoing degeneration, were observed in
      the white matter. Such cells were often being phagocytosed by the AMC. At 3-7
      days after the hypoxic exposure, the cytoplasm of many AMC contained a number of
      phagosomes whereas at 14-28 days a large amount of lipid accumulation was
      observed in them. AMC were labeled intensely with horseradish peroxidase (HRP)
      administered intraperitoneally following the hypoxic exposure. The phagocytosis
      of degenerating cells by the AMC and uptake of HRP by them indicates that these
      cells efficiently remove the degenerating cells/debris from the neonatal white
      matter following hypoxia in an attempt to protect it from any harmful substances
      that may be secreted by the degenerating cells or from serum derived substances
      that may enter the brain through blood circulation.

PMID- 10925165
TI  - Effects of a traditional Chinese medicine, Qing Nao Yi Zhi Fang, on glutamate
      excitotoxicity in rat fetal cerebral neuronal cells in primary culture.
AB  - Qing Nao Yi Zhi Fang (QNYZ), a traditional Chinese medicine, has been developed
      as a drug to be used for the prevention and treatment of vascular dementia.
      However, the mechanisms by which this drug affects vascular dementia remain
      unknown. We examined the effects of QNYZ serum on glutamate excitotoxicity in rat
      fetal cerebral neuronal cells in primary culture. Exposure of neuronal cells to
      glutamate leads to a decrease in the activities of cholinesterase, superoxide
      dismutase, and streptoavidin peroxidase, and an increase in lactate dehydrogenase
      release. These enzyme activities were restored to the levels in untreated cells
      by the addition of QNYZ serum. QNYZ serum suppressed the increased nitric oxide
      production induced by glutamate and prevented glutamate-mediated apoptosis. QNYZ
      serum also improved mitochondrial energy metabolism after glutamate exposure.
      These findings suggest that QNYZ has protective effects against glutamate
      mediated excitotoxicity in neuronal cells during ischemic brain injury.

PMID- 10925166
TI  - Protein kinase A activity is required for depolarization-induced proline-rich
      tyrosine kinase 2 and mitogen-activated protein kinase activation in PC12 cells.
AB  - Protein kinase A (PKA) plays an essential role in the depolarization-induced c
      fos expression in PC12 cells although the exact mechanism is unknown. Here we
      demonstrate that PKA is required for depolarization-induced activation of both
      extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein
      (MAP) kinase in PC12 cells. In addition, we have found that the depolarization
      induced tyrosine phosphorylation of proline-rich tyrosine kinase (PYK) 2, a key
      calcium-sensitive upstream mediator of MAP kinase activation, is profoundly
      blocked by PKA inhibition. In contrast to the depolarization-induced signaling,
      the ERK and PYK2 activation by bradykinin (1 microM), a G-protein coupled
      receptor agonist, was not blocked by PKA inhibition. These findings suggest that
      PKA inhibition prevents depolarization-induced PYK2/MAP kinase pathway
      activation, thereby inhibiting the early gene expression.

PMID- 10925167
TI  - Long-term treatment with haloperidol decreases the mRNA levels of complexin I,
      but not complexin II, in rat prefrontal cortex, nucleus accumbens and ventral
      tegmental area.
AB  - The effect of long-term treatment with haloperidol on gene expression of the
      presynaptic protein complexins was investigated in the discrete brain regions of
      rats, using reverse transcription-polymerase chain reaction. Four-week-treatment
      with haloperidol decanoate (25 mg eq/kg) produced a significant decrease in the
      mRNA levels of complexin I in the medial prefrontal cortex, nucleus accumbens and
      ventral tegmental area, but not in the striatum and substantia nigra. No
      significant changes in complexin II mRNA levels were observed in any brain region
      examined here. The reduced expression of complexin I may be associated with the
      haloperidol-induced depolarization block of mesocorticolimbic dopamine neurons.

PMID- 10925168
TI  - Repeated administration of high dose levodopa enhances hydroxyl radical
      production in the rat striatum denervated with 6-hydroxydopamine.
AB  - We examined whether levodopa (L-DOPA) might increase production of hydroxyl
      radicals in intact and dopamine-denervated rat striatum. Salicylate trapping
      combined with in vivo microdialysis provided measurements of 2,3-dihydroxybenzoic
      acid (2,3-DHBA) as a marker of hydroxyl radical production. Acute administration
      of high-dose L-DOPA (200, 500 mg/kg, i.p.) did not alter 2,3-DHBA levels in
      intact striatum or in striatum denervated with 6-hydroxydopamine. On the other
      hand, L-DOPA administration (200 mg/kg, i.p.) transiently increased 2,3-DHBA in
      dopamine-denervated striatum of rats after repeated administration of L-DOPA (200
      mg/kg, i.p., once daily for 16 days). The results indicated that repeated
      administration of high dose L-DOPA increased production of hydroxyl radicals in
      dopamine-denervated striatum.

PMID- 10925169
TI  - Dynorphin modulates dopamine D1-receptor mediated turning behavior in 6
      hydroxydopamine-lesioned rats.
AB  - We investigated if the potentiated turning response to a challenge with the
      partial dopamine D1 receptor agonist SKF-38393, as seen after priming with L
      dihydroxyphenylalanine (DOPA) of unilaterally 6-hydroxydopamine-lesioned rats,
      can be modulated by infusion of dynorphin A (1-17) in the striatum. Seventeen
      days after the 6-hydroxydopamine lesion, rats received intrastriatal dynorphin
      (0. 08 or 3.85 microg) followed by L-DOPA (50 mg/kg i.p.) and were challenged 3
      days later with SKF-38393 (3.0 mg/kg s.c.). Compared to controls, the lower dose
      of dynorphin caused an earlier onset of turning, while the higher dose decreased
      the response to SKF-38393. These findings suggest a dose-dependent modulatory
      role for striatal dynorphin in L-DOPA-priming of a D1-mediated behavioral
      response.

PMID- 10925170
TI  - Accumulation of human alpha-synuclein in different cytoskeletons in Lewy bodies
      in brains of dementia with Lewy bodies.
AB  - We investigated the origin of alpha-synuclein-immunoreactive components in Lewy
      bodies (LB) in brains of dementia with Lewy bodies (DLB) using
      immunohistochemistry and immunoelectron microscopy with anti-alpha-synuclein
      antibodies and anti-cytoskeleton antibodies. alpha-Synuclein-positive LB light
      microscopically consisted of phosphorylated neurofilament (PN)-positive LB,
      tubulin-positive LB and LB that were negative for both stains. Immunoelectron
      microscopically, PN-positive LB were composed of PN-positive and alpha-synuclein
      positive filamentous components, suggesting that these filamentous components
      originate from neurofilaments with partially reduced immunoreactivity and alpha
      synuclein accumulation. However, tubulin-positive LB were composed of tubulin
      positive and alpha-synuclein-positive tubular components, suggesting that these
      tubular components originate from microtubules with diffusely reduced
      immunoreactivity and alpha-synuclein accumulation. The results of the present
      study suggest that alpha-synuclein accumulates in different cytoskeletons in the
      LB in DLB brains presumably due to a blockage of axonal transport.

PMID- 10925171
TI  - Inhibition of the central heme oxygenase-carbon monoxide pathway increases 2
      deoxy-D-glucose-induced hypothermia in rats.
AB  - The present study was designed to test the hypothesis that carbon monoxide (CO)
      plays a role in 2-deoxy-D-glucose (2-DG)-induced hypothermia. The body
      temperature (T(b)) of awake, unrestrained rats was measured before and after
      systemic administration of 2-DG (50 mg/kg) and intracerebroventricular
      administration of zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG, a heme-oxygenase
      inhibitor, 200 nmol/4 microl). We observed a significant reduction in body
      temperature after 2-DG injection. ZnDPBG alone caused no significant change in
      body temperature. When the two treatments were combined, 2-DG-induced hypothermia
      was significantly increased. The data indicate that heme oxygenase-carbon
      monoxide pathway plays a key role in 2-DG-induced hypothermia, inhibiting 2-DG
      induced hypothermia.

PMID- 10925173
TI  - Independence of force production by digits of the human hand.
AB  - The hypothesis that handedness stems from a greater ability to produce
      independent forces in the digits of the preferred than the non-preferred hand was
      investigated in 20 right-handed males who made a sustained isometric flexion of
      the distal phalanx of a single digit (the instructed digit). Instructed flexion
      forces were accompanied by non-instructed forces in all other digits. Mean non
      instructed force was least when the thumb was the instructed digit, and increased
      progressively when the index, middle, ring, and little finger was the instructed
      digit. Both flexion and extension were recorded in non-instructed digits. There
      was no asymmetry in production of non-instructed force, and hence no evidence for
      greater independence of force production in the digits of the preferred than the
      non-preferred hand.

PMID- 10925172
TI  - An antisense investigation of the role of the gamma-aminobutyric acidB1 receptor
      subunit in Ca2+ channel modulation in rat sensory neurones.
AB  - Activation of gamma-aminobutyric acid(B) (GABA(B)) receptors in dorsal root
      ganglion (DRG) neurones leads to inhibition of calcium (Ca(2+)) channels. The
      role of the GABA(B1) receptor subunit was assessed by its depletion achieved by
      microinjection of DRG neurones with an antisense (A/S) oligodeoxynucleotide
      (ODN). Control neurones were injected with a scrambled version of the A/S ODN
      (missense) or were not injected. Patch clamp recordings of Ca(2+) channel current
      were made two to four days after injection. GABA(B1) A/S substantially reduced
      the current inhibition induced by baclofen, a GABA(B) agonist. Therefore, most,
      if not all, native GABA(B) receptors which couple to Ca(2+) channels contain
      GABA(B1). Moreover, if native receptors are heterodimers of GABA(B1) and
      GABA(B2), then GABA(B2), in isolation, is unable to sustain coupling to Ca(2+)
      channels.

PMID- 10925174
TI  - Topical acetyl salicylate and dipyrone attenuate neurogenic protein extravasation
      in rat skin in vivo.
AB  - The effect of topically applied acetyl salicylic acid (ASA) and dipyrone on
      capsaicin-evoked protein extravasation was investigated by dermal microdialysis
      in rat. After a baseline of 75 min, capsaicin (1%) was applied epicutaneously
      under occlusion for 75 min above the capillaries. Topical capsaicin stimulation
      induced neurogenic protein extravasation with a mean increase of protein
      concentration in the perfusate of 165+/-27% (mean+/-SEM; n=15), whereas in sham
      stimulated sites protein concentration decreased to 73+/-7% of the prestimulation
      value (n=6). ASA (2-200 mg/ml) and dipyrone (3-300 mg/ml) dose-dependently
      reduced the capsaicin induced protein extravasation to 118+/-23% (ASA, 200 mg/ml;
      n=8) and 72+/-9% (dipyrone, 300 mg/ml; n=8) of the prestimulation value. ASA and
      dipyrone antagonized the excitatory effects of capsaicin on skin nociceptors and
      thus suppressed the neurogenic protein extravasation.

PMID- 10925175
TI  - Brain activation profiles in dyslexic children during non-word reading: a
      magnetic source imaging study.
AB  - The purpose of the study was to identify spatiotemporal brain activation profiles
      associated with phonological decoding in dyslexic children using magnetic source
      imaging. For this purpose maps of regional cerebral activation were obtained from
      eleven children diagnosed with dyslexia and ten children without reading problems
      during engagement in a pseudoword rhyme-matching task. All dyslexic children
      showed aberrant activation maps consisting of reduced activity in temporoparietal
      areas in the left hemisphere (including the posterior part of the superior
      temporal, angular and supramarginal gyri) and increased activity in the right
      homotopic region. In contrast, the two groups of children did not differ in the
      degree of activity in basal temporal areas that typically precedes
      temporoparietal activation. This is the first study to demonstrate the existence
      of distinct activation profiles associated with phonological decoding in
      individual dyslexic children.

PMID- 10925176
TI  - Effects of spectral complexity and sound duration on automatic complex-sound
      pitch processing in humans - a mismatch negativity study.
AB  - The pitch of a spectrally rich sound is known to be more easily perceived than
      that of a sinusoidal tone. The present study compared the importance of spectral
      complexity and sound duration in facilitated pitch discrimination. The mismatch
      negativity (MMN), which reflects automatic neural discrimination, was recorded to
      a 2. 5% pitch change in pure tones with only one sinusoidal frequency component
      (500 Hz) and in spectrally rich tones with three (500-1500 Hz) and five (500-2500
      Hz) harmonic partials. During the recordings, subjects concentrated on watching a
      silent movie. In separate blocks, stimuli were of 100 and 250 ms in duration. The
      MMN amplitude was enhanced with both spectrally rich sounds when compared with
      pure tones. The prolonged sound duration did not significantly enhance the MMN.
      This suggests that increased spectral rather than temporal information
      facilitates pitch processing of spectrally rich sounds.

PMID- 10925177
TI  - Regulation and immunhistochemical localization of nitric oxide synthases and
      soluble guanylyl cyclase in mouse spinal cord following nociceptive stimulation.
AB  - The localization and regulation of neuronal nitric oxide synthase (nNOS),
      inducible nitric oxide synthase (iNOS) and soluble guanylyl cyclase (sGC) were
      assessed in the spinal cord of mice stimulated by an intraplantar injection of
      zymosan. Both, nNOS and iNOS were upregulated in the dorsal horns of the spinal
      cord in response to the zymosan challenge. While nNOS was found in neurons of
      superficial laminae iNOS occurred in astrocytes. Thus, astrocytes might be
      involved in the processing of nociceptive stimuli. Expression of sGC was not
      affected by zymosan treatment. It was found exclusively in nerve fibers
      suggesting that it was predominantly localized to the presynaptic neuron. This
      supports the hypothesis that nitric oxide (NO) acts as retrograde messenger in
      spinal nociceptive processing.

PMID- 10925180
TI  - Corrigendum to 'Protection against ischemic injury in primary cultured mouse
      astrocytes by bis(7)-tacrine, a novel acetylcholinesterase inhibitor'

PMID- 10925181
TI  - Forty years in burns research - the postburn inflammatory response.

PMID- 10925179
TI  - Mechanical and thermal hypersensitivity develops following kainate lesion of the
      ventral posterior lateral thalamus in rats.
AB  - Damage to the ventral-posterior lateral nucleus (VPL) of the thalamus or its
      afferent pathways can produce moderate to severe on-going pain and pain in
      response to normally innocuous stimuli (allodynia) and hypersensitivity to mildly
      noxious stimuli (hyperalgesia). The present study measured the responses to
      mechanical and thermal stimuli before and 2, 8, 24 and 48 h after a kainate
      induced lesion of the VPL in male rats. Compared with control animals,
      hypersensitivity to mechanical stimulation of the hindpaw was apparent by 24 h
      post-lesion. At 48 h, the frequency of mechanical response increased from a
      baseline response frequency of 17+/-4.7 to 46+/-11.6%. Thermal withdrawal
      latencies 48 h after the lesion decreased from a baseline latency of 9.9+/-1.8 to
      5.3+/-0.4 s. It is concluded that a neurotoxic lesion of the VPL results in a
      delayed onset of mechanical and thermal hyperalgesia. This study suggests a
      potential model for studying the basic mechanisms and potential therapies for
      central pain syndrome.

PMID- 10925178
TI  - mRNA expression of kidney-specific ClC-K1 chloride channel in single-cell reverse
      transcription-polymerase chain reaction analysis of outer hair cells of rat
      cochlea.
AB  - Outer hair cells (OHCs) of cochlea have been suggested to have Cl(-) channels
      sensitive to an ototoxic diuretic, furosemide. We therefore examined whether
      kidney-specific chloride channels (ClC-K1 and ClC-K2) and ClC-5 are also
      expressed in OHCs of rat cochlea, assuming that these channels might be the
      targets of oto-nephrotoxic drugs, by single-cell reverse transcription-polymerase
      chain reaction (RT-PCR) technique. Single-cell RT-PCR revealed the presence of
      transcripts of ClC-K1 in OHCs which was verified by DNA sequencing, while ClC-K2
      and ClC-5 were not detected. The possible roles of ClC-K1 in OHCs are discussed.

PMID- 10925182
TI  - Domestic burns prevention and first aid awareness in and around Jamshedpur,
      India: strategies and impact.
AB  - This article highlights the strategy for awareness creation regarding burns
      prevention and first aid and its impact in and around the steel-producing city of
      Jamshedpur, India. This is a joint venture of the Burns Centre and the Medico
      Social Welfare Unit of the Tata Main Hospital, Jamshedpur in collaboration with
      the Social Service Division of Tata Steel and city schools. The first phase of 5
      years has been devoted to general awareness building in the population through
      two main programmes, namely "Community Awareness Programmes" for the target group
      of ladies and teenage girls and "School Education Programmes" for the target
      group of school children of Standard 8 in the steel-producing city. These
      programmes include audio-visual presentations as well as face to face
      interactions regarding structure and arrangements in the kitchen, floor level
      cooking, clothing while cooking, careful use of electrical appliances, pressure
      stoves, etc. The discussions also include suicidal and homicidal burns prevention
      strategies. Various competitions for the target group provide feedback on
      programmes. The growing awareness about burns prevention among school children
      and community members, and steady increase in the number of patients who use
      water as first aid, speak about the success of the strategies.

PMID- 10925183
TI  - The effect of a tissue engineered bilayered living skin analog, over meshed split
      thickness autografts on the healing of excised burn wounds. The Apligraf Burn
      Study Group.
AB  - The potential of Apligraf(R) (Graftskin) (Organogenesis Inc., Canton, MA), to
      improve cosmetic and functional outcomes when applied over meshed split thickness
      autografts was evaluated in a multicenter, randomized within patient controlled
      clinical trial. Experimental treatment sites had Apligraf(R) placed over meshed
      autograft while control sites were treated with meshed autograft covered with
      meshed allograft, or meshed autograft not covered by a biologic dressing. Forty
      patients were entered into this study of which 38 were evaluable. There was no
      difference in the percent take of autograft in the presence or absence of
      Apligraf(R) or in the median number of days to greater than 75% take of
      autograft. At the completion of the study 22 (58%) of the Apligraf(R) sites were
      rated superior to the control sites by the investigators, 10 (26%) were rated
      equivalent to the control and six (16%) were rated worse than control (p=0.
      0037). Pigmentation, in the Apligraf(R) group was significantly better than
      control and by month 24, 17 (45%) Apligraf(R) sites had normal pigmentation
      compared with five (13%) control sites (p=0. 0005). Similarly by month 24, 18
      (47%) patients had normal vascularity at the Apligraf(R) site compared with six
      (16%) patients at the control site. Improvements in pliability were observed with
      Apligraf(R) over control treatment within the first week of treatment. At month
      24, 23 (61%) patients had normal height at the Apligraf(R) site compared to 14
      (37%) with normal height at the control site (p=0.0117). Vancouver burn scar
      scores were shown to be statistically better at Apligraf(R) sites compared to
      control at all time points from week 1 to month 24. These results indicate that
      Apligraf(R) is a suitable and clinically effective treatment for burn wounds when
      applied over meshed autografts. Furthermore, cosmetic and functional advantages
      with Apligraf(R) were demonstrated when applied over meshed autograft compared to
      the current standard treatments of meshed autografts.

PMID- 10925184
TI  - Cutaneous herpetic infections complicating burns.
AB  - Many people harbor herpes simplex virus, often with a known history of "cold
      sores". During the relatively immunosuppressed state associated with a serious
      burn, recrudescence of such infections can occur. We report four adults and two
      children who developed severe herpetic ulceration, over the face and neck in five
      patients and in a partial thickness wound in one patient. Herpetic infection was
      diagnosed by culture and direct immunofluorescence testing and treatment was
      immediately instituted with systemic and topical Acylovir(R) (Zovirax, Glaxo
      Wellcome). Ulceration healed under treatment and did not leave visible scarring
      in any of the patients. Although these infections are rapidly progressive, they
      respond to prompt treatment with antiviral chemotherapy. Rapidly progressive
      vesicles and ulceration appearing on the face or in the wounds of burn patients
      should prompt immediate evaluation for herpetic infection.

PMID- 10925185
TI  - A toddler with burns, stomatitis, and skin graft loss.
AB  - The authors report on a healthy 21-month-old toddler with 13% TBSA deep scald
      burns who was successfully grafted (take 100%). In the immediate postoperative
      phase, the patient developed classical aphthous stomatitis and subsequent herpes
      viremia leading to severe viral "graftitis". Although immediately administered
      intravenous acyclovir therapy appeared to be effective, one third of grafts were
      lost and had to be replaced. The lesson from this case is 2-fold: Herpes
      infection may threaten even perfectly engrafted fresh skin transplants, and,
      freshly grafted or soon to be grafted burn patients should be given intravenous
      antiviral therapy as soon as a herpes infection is diagnosed.

PMID- 10925186
TI  - The axial bilobed flap for burn contractures of the axilla.
AB  - The axial bilobed flap, based on the transverse and descending branches of the
      circumflex scapular artery, was used to successfully reconstruct burn
      contractures of the axilla. The main advantages of this flap are that the donor
      site is closed primarily, it provides an adequate amount of healthy and pliable
      skin with an excellent blood supply and no chance of contraction, and it is an
      easy technique. In this paper, two cases are presented.

PMID- 10925187
TI  - Heparin-free hemodialysis in the treatment of hypernatremia in severely burned
      patients.
AB  - BACKGROUND: Hypernatremia in severely burned patients is associated with high
      morbidity and mortality rates. As the causes of hypernatremia in major burn
      patients are still not clear, hemodialysis is the method of choice for the
      treatment. While hemodialysis is effective for the control of hypernatremia, it
      can cause bleeding complications that may be fatal for burn patients with
      extensive wounds and potential gastro-intestinal mucosal damage. CLINICAL DATA:
      In the present study heparin-free hemodialysis in which the heparin is firmly
      absorbed to the haemofiltration membrane, hemophan, dispensed with systemic use
      of heparin. In two extensively burned patients with burn area of 100% TBSA and
      98% TBSA respectively and hypernatremia with serum sodium concentration as high
      as 169 and 158 mmol/l respectively, heparin-free hemodialysis was performed five
      times and three times each. RESULTS: Hypernatremia was satisfactorily corrected
      with no interference to the coagulation system in the two patients as indicated
      by clinical observation and biochemical analysis. The patient with burn area of
      98% TBSA survived and the patient with burn area of 100% TBSA died of wound
      coverage failure 6 weeks after injury because of non-availability of autograft.
      CONCLUSION: Heparin-free hemodialysis is an effective and safe method in the
      treatment of hypernatremia in extensively burned patients.

PMID- 10925188
TI  - Veno-venous continuous renal replacement therapy for burned patients with acute
      renal failure.
AB  - From 1995 to 1998, 12 burned patients with acute renal failure (ARF) were treated
      by veno-venous continuous renal replacement therapy (CRRT) at the Burn Unit of
      Hotel-Dieu de Montreal. Their mean (+/-SD) age was 51+/-12 years, and the mean
      burned surface covered 48.6+/-15.8% of total body surface area. All patients were
      mechanically ventilated and presented evidence of sepsis. The mean delay before
      occurrence of ARF was 15+/-6 days and ARF was mainly related to sepsis and
      hypotension. Main reasons for CRRT initiation were azotemia and fluid overload. A
      total of 15 CRRT modalities were applied (12 continuous veno-venous
      hemodiafiltration, CVVHDF; two continuous veno-venous hemofiltration, CVVH; and
      one continuous veno-venous hemodialysis, CVVHD) over 14+/-13 days. For CRRT, nine
      patients received heparin and three were not anticoagulated. Mean values for
      dialysate and reinjection flow rates were 1134+/-250 ml/h and 635+/-327 ml/h,
      respectively. Admission weight was 78.8+/-12.7 kg with a mean weight gain before
      CRRT initiation of 10.0+/-5.8 kg and a mean weight loss during CRRT of 8.9+/-5.5
      kg. Nine patients received enteral plus parenteral nutrition, and three,
      parenteral nutrition only; the total caloric intake was 31.5+/-7.0 kcal/kg/day
      and protein intake, 1.8+/-0.4 g/kg/day. The normalized protein catabolic rate
      (nPCR) was evaluated at 2.28+/-0.78 g/kg/day during CRRT. The mortality rate was
      50%. The six survivors all recovered normal renal function with four of them
      requiring intermittent hemodialysis for short periods. In conclusion, veno-venous
      CRRT is particularly well suited for this selected population allowing smooth
      fluid removal and aggressive nutritional support.

PMID- 10925190
TI  - Pediatric burns induced by psoralens in Saudi Arabia.
AB  - Over a 5-year period, three children with psoralen-induced burns were seen. All
      children were on treatment for vitiligo with a psoralen oil and burns were
      sustained from unsupervised sun exposure while playing outdoors. The burn wound
      was partial thickness and involved 6-40% of the total body surface area. All
      wounds healed without infection or contracture with topical silver sulfadiazine.
      However, the previously normal skin in phototoxic areas became significantly
      hyperpigmented while the areas with vitiligo remained hypopigmented. Differences
      between psoralen-induced burns and other second degree sunburns unrelated to
      psoralens are discussed.

PMID- 10925191
TI  - A small contact burn injury requiring upper limb amputation.
AB  - An elderly, demented, man was referred with a fairly small contact burn to the
      medial side of his left arm and forearm. The thermal injury had caused ischaemia
      of the forearm and hand. Thrombosis of the underlying brachial artery was
      suspected, and the only surgical option was amputation. This is an unusual but
      devastating complication of a contact burn. Those particularly at risk of this
      injury include the demented, elderly, epileptics and neuropathics, who may lie
      helpless or unaware of prolonged contact with warm objects.

PMID- 10925189
TI  - Artificial skin, split-thickness autograft and cultured autologous keratinocytes
      combined to treat a severe burn injury of 93% of TBSA.
AB  - Despite refinements in burn shock resuscitation, improvements in surgical
      techniques, advances in intensive care medicine and the presence of very expert
      surgeons, the treatement of patients with severe burns exceeding 60% TBSA remains
      a big challenge. A major problem in the treatment of severe burn injuries is the
      lack of autologous skin. In selected cases cultured epidermal autograft (CEA) may
      be used. However, they are available only 2-3 weeks after biopsy, thus requiring
      a temporary wound closure after necrosectomy. A new option is Integra(TM), an
      artificial skin consisting of a bilayer membrane system. The three-dimensional
      porous matrix from bovine tendon collagen and a glycosaminoglycan layer is
      covered by a silicon sheet. The latter prevents fluid loss from the wounds and
      serves as a barrier against germ invasion. After adequate vascularisation of the
      dermal template, the silicon layer is removed and replaced by a thin autograft.
      We present a 26-year old male who sustained a 93% TBSA burn injury (60% full
      thickness burn, 33% partial-thickness burn). He was treated with artificial skin,
      split-thickness autograft and CEA in combination. The clinical history and the
      follow-up of approx. 1 year are presented and the results discussed. We consider
      the survival of this patient being a result of the therapeutic progress of the
      recent decades.

PMID- 10925192
TI  - A high voltage electrical burn of lung parenchyma.
AB  - High voltage electrical trauma may cause severe visceral injuries. We report a
      case of direct electrical injury to the lung parenchyma, without evidence of any
      thoracic wall contact injury, in an electrician who sustained a 20 kV-electrical
      shock while working in a substation cubicle. The diagnosis of a true electrical
      burn of the left lower lobe was suggested early on by imaging and then confirmed
      by surgical exploration, histological findings and the significant improvement of
      the patient's condition following resection of the infarcted lobe. All possible
      causes of bronchial and pulmonary pathologies in such a context were ruled out.
      The fatal outcome of two previous similar cases and the generally high mortality
      of any electrical visceral injury support early surgical management as the only
      rational life-saving treatment. Current pathophysiological knowledge
      substantiates the theory of an isolated visceral injury located far away from the
      contact wounds. However, the pathogenesis of such severe injuries is not entirely
      understood.

PMID- 10925194
TI  - Hyperemia of the intraperitoneal organs associated with scald burn.
AB  - A 65-year-old man with a history of cerebral infarction sustained scald burns
      over 54% of the body surface. In spite of adequate fluid therapy, respiratory
      management with an artificial ventilator, and continuous hemodiafiltration, the
      patient died on day 5 post-admission. Autopsy revealed necrotic change on the
      surface of the liver, and necrosis and perforation of the ileum. Histologic
      examination showed necrosis of the hepatocytes lining the surface and necrosis of
      the hepatocytes and congestion in the central area of the liver. We speculated
      that systemic responses to the extensive burn resulted in hyperemia of the
      intraperitoneal organs, thereby inducing acute liver failure and the subsequent
      development of multiple organ failure.

PMID- 10925193
TI  - Abdominoperineal electrical injury involving urogenital organs.
AB  - Although the incidence of electrical burns is not very high this incidence is
      rising in India. The residual effects of electrical burns are sometimes very
      severe and long lasting, if not managed properly. This case report is of a
      patient who sustained severe electrical burns over his left arm, lower abdomen
      and perineal area. The injuries were so severe that life-saving disarticulation
      of the limb together with excision of the involved pubic bone and genitalia and
      suprapubic urinary diversion was done. During follow up an unusual finding was
      noticed. There was a peritubal leak with no drainage from the catheter and on
      removal of the catheter, a manual examination of the urinary bladder revealed a
      stone which was removed at the same time. Following removal of the stone two
      ureteric openings with the trigone were seen and it was concluded that the
      granulating tissue was actually the posterior wall of the bladder. This was then
      mobilized and reposited into the abdomen. The deficient lower abdomen was
      reconstructed with a tensor fascia lata flap. A penile reconstruction for the
      patient is under consideration.

PMID- 10925196
TI  - An unusual iatrogenic burn from a heated dental instrument.
AB  - The following report describes an unusual iatrogenic contact burn from a heated
      dental instrument. The potential hazard of inflicting a contact burn using a
      glass bead sterilizer must be kept in mind.

PMID- 10925195
TI  - Diathermy and alcohol skin preparations - a potential disastrous mix.
AB  - Disinfectant solutions with high concentrations of alcohol are used in many
      operating theatres as skin preparation. We present two cases of burns as a result
      of accidental ignition of the solution and list precautionary measures for the
      use of these solutions.

PMID- 10925197
TI  - Replication of UV-damaged DNA: new insights into links between DNA polymerases,
      mutagenesis and human disease.

PMID- 10925198
TI  - DNA sequence analysis of the complete mitochondrial genome of the green alga
      Scenedesmus obliquus: evidence for UAG being a leucine and UCA being a non-sense
      codon.
AB  - The complete DNA sequence of the mitochondrial genome of the chlorophyceen alga
      Scenedesmus obliquus was determined. The circular genome of 42781bp contains a
      basic set of 13 mitochondrial genes, which are conserved among plant or algal
      chondriomes. In addition, two scrambled rRNA and 27 tRNA genes are present,
      together with four intronic sequences (group I and II) and five open reading
      frames (ORFs), which show no significant homology to other ORFs from organellar
      genomes. The comparison with deduced amino acid sequences from 13 conserved
      mitochondrial genes gives rise to the conclusion that two deviations from the
      standard genetic code must be present in S. obliquus mitochondria: (i) UAG codes
      for leucine as was already found in some other algal mitochondria; (ii) UCA is a
      stop codon, which seems unique for mitochondrial genomes. This was supported by
      our finding that a tRNA-Leu gene possesses a UCA anticodon and by a missing tRNA
      serine, able to decode the UCA codon. Consistent with these data is the absence
      of any UCA codon from conserved mitochondrial ORFs. This codon occurs only close
      to the end of all ORFs, while UAA or UGA codons are found at some distance from
      any conserved ORF. Codon changes by RNA editing can be excluded, since RT-PCR
      analysis does not reveal any evidence for post-transcriptional RNA modifications
      of the primary transcript.

PMID- 10925199
TI  - Characterization of the structure and expression of a highly conserved ribosomal
      protein gene, L9, from pea.
AB  - The eukaryotic ribosomal protein (RP) L9 is highly conserved in nature, and its
      gene is expressed to high levels in the actively growing tissues of pea. The
      transcriptional activity of the gene is highest in root, cambial and shoot
      meristems and immature tissues of the plant. Promoter deletion analysis using
      constructs employing the reporter gene gus were stably transferred into tobacco
      and revealed that the fully functional promoter is found in the first 316bp
      upstream from the start codon. Transgenic pea plants carrying one of these
      constructs show that translational efficiency mirrors gene transcription; gene
      expression appears to be developmentally regulated at the level of transcription.
      The coding region of the gene shares 80% amino acid homology with Arabidopsis and
      76% homology with rice. Comparisons of the gene structure to that of the human,
      fruit fly, yeast, and Arabidopsis homologues reveal a close relationship in both
      promoter structure and intron insertion sites with the Arabidopsis gene. A
      nucleotide sequence alignment of the pea gene with other plant RP genes revealed
      that a sequence, -TTAGGGTTTT-, was commonly found in the forward and/or the
      inverted orientation at or near the TATA boxes of the promoters of these genes
      and may have a role in regulating the coordinate production of the RP genes in
      plants.

PMID- 10925200
TI  - The LAMB1 gene from the clubmoss, Lycopodium annotinum, is a divergent MADS-box
      gene, expressed specifically in sporogenic structures.
AB  - Transcription factors encoded by the large MADS-box gene family have important
      developmental functions in angiosperms, the flowering plants. Mutations in
      certain MADS-box genes are known to cause homeotic alterations in floral organ
      identity, and the establishment of floral organ identity is the most well-studied
      developmental process in which MADS-box genes are known to function. Our interest
      is in the potential connection between the duplication history of this gene
      family and the evolutionary origin of the structures that the different MADS-box
      genes developmentally regulate in plants. Previous studies have demonstrated that
      the origin of the MADS-box genes that control floral organ identity predate the
      evolutionary origin of the flower itself, since gymnosperms have genes that are
      orthologous to angiosperm floral homeotic MADS-box genes, whereas ferns appear to
      lack such genes. Here we report on the isolation of a MADS-box gene from
      Lycopodium annotinum, which belongs to the clubmosses, the phylogenetic sister
      group to other vascular plants. The gene, LAMB1, in the sporophyte is expressed
      exclusively in the reproductive structure, the strobilus, during sporogenesis.
      LAMB1 is similar to other plant MADS-box genes in that it contains a MADS-box as
      well as a second conserved element, a K-box. However, it differs in length and in
      exon/intron structure in the region between the MADS- and K-box, and also in the
      length and structure of the C-terminal region. A phylogenetic analysis indicates
      that LAMB1 is not closely related to other plant-type MADS-box genes, and may
      represent one of the basal branches in the phylogenetic tree of plant MADS-box
      genes.

PMID- 10925201
TI  - Sequence and expression analysis of a surface antigen gene family of the
      rickettsia Anaplasma marginale.
AB  - The tick-borne rickettsial organism, Anaplasma marginale, causes a disease in
      cattle of world-wide economic significance. This disease, anaplasmosis, is
      characterized by severe hemolytic anemia, high levels of rickettsemia and, often,
      death in animals over 3years of age. Animals that survive acute infection remain
      carriers, with continuous sub-microscopic cycles of rickettsemia that can persist
      for the lifetime of the animal. In the search for potential recombinant
      immunogens, it was discovered that several surface proteins of A. marginale
      encode polymorphic multigene families. Despite the small size of the genome
      (approx. 1250kb), these surface antigen gene families comprise greater than 2% of
      the genome. We present here a mapping, sequencing and expression analysis of five
      complete or partial genes encoding MSP1b in a Florida strain of A. marginale. Two
      genes are complete; they encode mRNA that is translated into polypeptide
      products. Three genes are incomplete and appear to be derived from the complete
      genes by a series of segmental intragenic recombinations. In two of the
      incomplete genes, 5' sequence in the incomplete genes is 3' sequence in the
      complete genes. Recombination within these gene families may generate diversity
      in surface antigens through combinatorial rearrangements. This could contribute
      to persistence in the chronic infections caused by A. marginale and related
      rickettsiae.

PMID- 10925203
TI  - Construction and application of mycobacterial reporter transposons.
AB  - The transposon Tn5367, which is a derivative of the mycobacterial insertion
      sequence IS1096, was modified by introducing novel genes to produce reporter
      transposons which can be used to generate transposon insertion libraries
      containing mycobacterial gene or operon fusions. A plasmid that is temperature
      sensitive for replication in mycobacteria was used to deliver promoterless lacZ
      or aph reporter genes to Mycobacterium smegmatis as transcriptional (lacZ), or
      translational ('aph) fusions. Mutants containing lacZ produced varying
      intensities of blue colour on indicator media. This reporter activity could be
      used as a quantitative measure of promoter strength. Mutants displaying varying
      levels of resistance to kanamycin were obtained by transpositional insertion of
      the 'aph reporter lacking a promoter, ribosome binding site and start codon to
      form functionally active translational fusions. Finally, inclusion of the
      R6Kgamma origin within Tn5367 allowed transposon insertions to be rescued in an
      Escherichia coli host strain permissive for the replication of this origin. This
      study demonstrates that transcriptional and translational reporter derivatives of
      Tn5367 are functional, and they supplement the growing range of molecular tools
      available for the study of mycobacteria.

PMID- 10925202
TI  - Sequence diversity of intervening sequences (IVSs) in the 23S ribosomal RNA in
      Salmonella spp.
AB  - Intervening sequences (IVSs) occur sporadically in the rrl (ribosomal RNA large)
      genes for 23S ribosomal RNA (rRNA) at helix-25 (base pair 550) and helix 45 (base
      pair 1170) in several bacterial genera, including Salmonella, Yersinia, Proteus,
      and Providencia, representing the Enterobacteriaceae, but are missing from other
      genera such as Escherichia. These sequences are transcribed, but later excised
      without re-ligation during RNaseIII processing of the rRNA, resulting in
      fragmented 23S rRNA. The IVSs from 22 strains of the SARB (Salmonella Reference
      Collection B) set were amplified by PCR and sequenced.IVSs with 90% or more
      sequence identity were placed in the same family; Salmonella has three families
      of IVSs in helix-25 (A, B, and C) and two in helix-45 (M and O). The rRNA
      secondary structure for the IVSs predicted from the mfold program reveals a
      primary stem of about 14bp, which is the postulated RNaseIII cleavage site, and a
      secondary region of stems and loops. The primary stem is considerably well
      conserved, with a high rate of compensatory mutations (positional covariants),
      confirming the reality of the secondary structure and indicating that removal of
      the IVSs exerts a positive selective pressure to retain the secondary structure.
      The pattern of possession and presence of families of IVSs was diverse and could
      not be related to the proposed ancestry of the strains as revealed by the multi
      locus enzyme electrophoresis pattern of the strains, suggesting that the IVSs are
      transferred between strains by lateral transfer. Helix-25 IVSs from families A,
      B, and C of Salmonella and D of Proteus, which share almost identical primary
      stems, are placed in superfamily I, while the primary stems of other IVSs from
      Proteus and Providencia are unrelated to superfamily I and are thus placed into
      superfamily II; this indicates lateral transfer of members of superfamily I
      between Proteus and Salmonella, but an independent origin of IVSs of superfamily
      II in Proteus and Providencia.

PMID- 10925204
TI  - Identification of genes in the genome of the archaeon Methanosarcina mazeii that
      code for homologs of nuclear eukaryotic molecules involved in RNA processing.
AB  - A 2.6kb fragment of chromosomal DNA from the archaeon Methanosarcina mazeii was
      sequenced and analyzed, and it was found to contain coding regions for three
      proteins that were 321, 234, and 193 amino acids (aa) in length. Homologs of the
      321-aa protein were found in all archaeal genomes examined, but not in eukaryotic
      or bacterial genomes, with one exception in the latter. The protein with 234aa
      (named PrpM) was most similar to the putative protein Prp31p from
      Methanobacterium thermoautotrophicum, while the 193-aa protein (named FibM) was
      identified as an archaeal fibrillarin homolog. Prp and fibrillarin proteins are
      involved in RNA processing in eukaryotes, but their functions in archaea are not
      yet understood. The M. mazeii PrpM was also similar to three proteins from
      Saccharomyces cerevisiae: Prp31p, Nop56p, and Nop58p. Prp31p is a pre-mRNA
      processing protein, while Nop56p and Nop58p are involved in rRNA processing and
      interact with fibrillarin. No homologs of either protein were found in bacteria.
      The archaeal fibrillarin was shorter than its eukaryotic counterpart because it
      lacked the N-terminal glycine-arginine-rich (GAR) domain, present in most
      eukaryal homologs. The archaeal prp and fibrillarin gene homologs were found
      adjacent to each other, whereas in eukarya these genes are on separate
      chromosomes. Sequence signatures typical of the eukaryal molecules were
      identified in the M. mazeii and the other archaeal molecules studied. The close
      proximity of the prp and fib genes raises the possibility of a Prp-fibrillarin
      interaction in archaea.

PMID- 10925205
TI  - Isolation and characterization of a novel PDGF-induced human gene.
AB  - Using a differential display RT-PCR strategy to identify novel growth-factor
      induced transcripts, we cloned and characterized the human homolog of yeast
      NOP5/NOP58, whose gene product has been implicated in the execution of early pre
      rRNA processing steps. Human NOP5 cDNA was isolated from an M426 fibroblast cDNA
      library. Determination of the cDNA nucleotide sequence revealed an open reading
      frame of 1587 nucleotides encoding a predicted gene product of 529 amino acids
      and mass of 59554Da. The yeast and human NOP5 gene products were found to share
      63% homology and 46% identity. NOP5 mRNA was induced within 2h of platelet
      derived growth factor (PDGF) treatment of human M426 fibroblasts. Pretreatment
      with cycloheximide enhanced, while actinomycin blocked induction of the NOP5
      transcript. In vitro translational analysis of the cDNA revealed a 60kDa species,
      consistent with the predicted molecular weight of the gene product. Ubiquitous,
      but differential NOP5 mRNA expression was revealed after Northern blot analysis
      of total RNA from several human tissues. Moreover, NOP5 mRNA expression was also
      demonstrated in cell lines of fibroblast, epithelial, and myeloid origin. A
      highly charged carboxy terminal domain and consensus phosphorylation sites were
      identified. The presence of potential regulatory elements, together with growth
      factor induction and widespread expression is consistent with the hypothesis that
      the NOP5 gene product may play a role in fundamental cellular growth processes.

PMID- 10925206
TI  - Structural similarities and evolutionary relationships in chloride-dependent
      alpha-amylases.
AB  - The alpha-amylase sequences contained in databanks were screened for the presence
      of amino acid residues Arg195, Asn298 and Arg/Lys337 forming the chloride-binding
      site of several specialized alpha-amylases allosterically activated by this
      anion. This search provides 38 alpha-amylases potentially binding a chloride ion.
      All belong to animals, including mammals, birds, insects, acari, nematodes,
      molluscs, crustaceans and are also found in three extremophilic Gram-negative
      bacteria. An evolutionary distance tree based on complete amino acid sequences
      was constructed, revealing four distinct clusters of species. On the basis of
      multiple sequence alignment and homology modeling, invariable structural elements
      were defined, corresponding to the active site, the substrate binding site, the
      accessory binding sites, the Ca(2+) and Cl(-) binding sites, a protease-like
      catalytic triad and disulfide bonds. The sequence variations within functional
      elements allowed engineering strategies to be proposed, aimed at identifying and
      modifying the specificity, activity and stability of chloride-dependent alpha
      amylases.

PMID- 10925207
TI  - Human dbl proto-oncogene in 85 kb of xq26, and determination of the transcription
      initiation site.
AB  - The dbl oncogene is generated by substitution of the 5' portion of its normal
      counterpart with an unrelated human sequence. To analyze the genomic structure
      and transcriptional regulation of the dbl proto-oncogene, we have isolated human
      genomic clones containing the entire human proto-dbl gene, localized in Xq26.
      Restriction mapping of a 600kb YAC clone (yWXD311) placed proto-dbl about 50kb
      telomeric to the coagulation Factor IX gene. The genomic DNA fragment containing
      the 5' end of proto-dbl was subcloned into plasmid vectors and the nucleotide
      sequences of exon 1, the flanking intronic region and genomic DNA 5' of the first
      codon were determined. Sequence analysis of 85119bp from the region revealed the
      genomic structure of proto-dbl. It contains 25 exons coding for a 4.7kb
      transcript including large 5'- and 3'- (1218bp and 701bp, respectively)
      untranslated regions (UTRs). RNase protection and primer extension assays on RNA
      from medullary thyroid carcinoma (TT) cells, which normally express dbl, revealed
      a transcription start site 1218bp upstream of the ATG of the first exon. A 1.6kb
      genomic 5' of the translation start sites drives the expression of a CAT-reporter
      in transient transfections in the TT cell line, though lacking TATA or CAAT
      boxes.

PMID- 10925208
TI  - Androgen binding profiles of two distinct nuclear androgen receptors in Atlantic
      croaker (Micropogonias undulatus).
AB  - In the present study, the binding affinities of 28 androgens for two nuclear
      androgen receptors (AR), termed AR1 and AR2, in Atlantic croaker (Micropogonias
      undulatus) brain and ovarian tissues, respectively, were determined using
      competitive binding assays. The 5alpha-reduction of steroids, in general,
      increased the metabolite's binding affinity for AR2 while decreasing it for AR1.
      In addition, few androgens bound to AR1 with high affinity and modifications to
      the basic 3-ketone,4-ene,17beta-hydroxy structure of testosterone usually reduced
      its binding affinity for AR1. However, androgens with ketone groups at the 3- and
      17-position bound with high affinity to AR1 provided that the androgen had either
      a 5alpha-reduced A-ring or a third ketone group at the 11-position. This suggests
      that there may be several high affinity conformations that AR1 can occupy
      depending upon whether an androgen possesses a ketone or a hydroxyl group at the
      17-position. The binding of androgens to AR2 showed a more predictable pattern,
      5alpha-reduced steroids bound better than 4-ene steroids and any changes to the
      basic 3-keto,17-hydroxy motif of 5alpha-dihydrotestosterone lowered the binding
      affinity of a steroid. However, these structural changes often caused only minor
      decreases in binding affinity, such that AR2 has a broader affinity for androgens
      and a greater affinity than AR1 for structurally diverse androgens. Widely
      different androgen binding affinities of AR1 and AR2 suggest that these two
      nuclear androgen receptors may mediate the physiological actions of different
      androgens in teleosts.

PMID- 10925209
TI  - Synergistic anticancer activity of 1,25-dihydroxyvitamin D(3) and immune
      cytokines: the involvement of reactive oxygen species.
AB  - It was previously shown that 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3))
      enhances the cytotoxic activity of tumor necrosis factor alpha (TNFalpha),
      doxorubicin and menadione. A feature shared by these anticancer agents is the
      involvement of reactive oxygen species (ROS) in their action. In this work we
      found that 1, 25(OH)(2)D(3) acted synergistically with interleukin 1 beta (IL
      1beta) or interleukin 6 (IL-6) to inhibit the proliferation of MCF-7 breast
      cancer cells. The extent of the synergism was maximal at 1 nM, a concentration at
      which 1,25(OH)(2)D(3), acting singly, only marginally reduced the cell number.
      The thiol antioxidant, N-acetylcysteine (NAC) abolished the synergism between IL
      1beta or IL-6 and 1,25(OH)(2)D(3), but had only a small protective effect when
      the cytokines acted alone. NAC and reduced glutathione (GSH) protected MCF-7
      cells from cytotoxicity induced both by TNFalpha alone and by TNFalpha and
      1,25(OH)(2)D(3). A two-day exposure to TNFalpha caused a 27.7+/-3.1% (mean +/-
      SEM) reduction in GSH content. This effect increased to 46.4+/-5.5% by co
      treatment with 1, 25(OH)(2)D(3) which did not affect GSH levels on it own. We
      conclude that 1,25(OH)(2)D(3) can act synergistically with anticancer cytokines
      present in the tumor milieu and that ROS plays a mediatory role in this
      interaction.

PMID- 10925210
TI  - Steroid sulfatase inhibitor alters blood pressure and steroid profiles in
      hypertensive rats.
AB  - Our hypothesis is that the steroid sulfatase gene (Sts) may indirectly contribute
      to the modulation of blood pressure (BP) in rats with genetic hypertension. The
      steroid sulfatase enzyme (STS) catalyzes the conversion of estrone sulfate,
      dehydroepiandrosterone sulfate, cholesterol sulfate and glucocorticoid sulfates
      to their active nonconjugated forms. This causes the elevation of biologically
      active steroids, such as glucocorticoids, mineralcorticoids as well as
      testosterone, which may lead to increased BP. The main objective was to examine
      the effects of a steroid sulfatase inhibitor on blood pressure and steroid levels
      in rats with hypertensive genetic backgrounds. Three treatment groups, 5-15 weeks
      of age were used: controls, estrone and STS inhibitor (estrone-3-O-sulfamate),
      (n=8 per group). BP was taken weekly by tail cuff, and serum testosterone (T),
      estrogens (E), and plasma corticosterone (C) levels were measured by
      radioimmunoassay. BP was significantly reduced by the STS inhibitor in the
      strains with genetically elevated BP. Also the inhibitor alone significantly
      reduced plasma corticosterone in all strains compared to estrone treatment with a
      concomitant as well as significant rise in estrogens and reduction in
      testosterone and body weight.

PMID- 10925211
TI  - The role of IGF-I, cAMP/protein kinase A and MAP-kinase in the control of steroid
      secretion, cyclic nucleotide production, granulosa cell proliferation and
      preimplantation embryo development in rabbits.
AB  - The aim of this study was to investigate the actions of insulin-like growth
      factor I (IGF-I) on the secretory and proliferative functions of rabbit ovarian
      cells and on early embryogenesis. It was found that addition of IGF-I at a lower
      concentration (1 ng/ml) stimulated progesterone secretion by cultured rabbit
      granulosa cells, whilst higher concentrations of IGF-I (10, 100 ng/ml) were
      inhibitory. IGF-I had no effect on estradiol secretion. Cyclic AMP secretion was
      slightly increased after addition of IGF-I at 10 ng/ml, but not by higher
      concentrations. Cyclic GMP secretion was stimulated by IGF-I at 100 ng/ml only. A
      blocker of protein kinase A, Rp-cAMPS, did not alter progesterone and estradiol
      secretion but did prevent the action of IGF-I on progesterone secretion. An
      immunocytochemical study demonstrated that IGF-I significantly increased the
      proportion of proliferating cell nuclear antigen-positive (PCNA-positive) cells.
      Rp-cAMP did not change cell proliferation but partially prevented the
      proliferation-stimulating effect of IGF-I. IGF-I (100 ng/ml) significantly
      increased the proportion of divided zygotes and the number of embryos reaching
      the morula/blastocyst stage. Blockers of PKA, Rp-cAMPS and KT5720, reversed the
      effects of IGF-I on zygote cleavage and embryo development. Addition of IGF-I
      (100 ng/ml) significantly increased MAPK within the cells (proportion showing
      immunoreactivity to ERK-1 and ERK-3 antibodies and intensity of a 42 kDa band
      related to ERK-2). Rp-cAMPS suppressed the basal ERK-2 immunoreactivity but not
      that of ERK-1 or ERK-3. It completely inhibited the IGF-I-induced activation of
      ERK-3 but not that of ERK-1 or ERK-2. This in vitro study demonstrates that IGF-I
      is a potent stimulator of ovarian secretion, proliferation and embryogenesis in
      rabbit. Its effects are mediated by cAMP/PKA- and, probably by, MAPK-dependent
      intracellular mechanisms.

PMID- 10925212
TI  - Subunits of neurosteroid sulfatase from bovine brain.
AB  - We have purified the neurosteroid sulfatase (NSS) from Triton X-100 solubilized
      microsomes of bovine brain about 100-fold. The purified enzyme is composed of two
      catalytic units (MW: 57 kDa) and two regulatory units (MW: 38 kDa), making it an
      alpha(2)beta(2) heterotetramer, whose apparent molecular weight was 180 kDa by
      gel filtration in the presence of Triton X-100.

PMID- 10925213
TI  - Elevated steroid sulfatase expression in breast cancers.
AB  - In situ estrogen synthesis makes an important contribution to the high estrogen
      concentration found in breast cancer tissues. Steroid sulfatase which hydrolyzes
      several sulfated steroids such as estrone sulfate, dehydroepiandrosterone
      sulfate, and cholesterol sulfate may be involved. In the present study, we
      therefore, assessed steroid sulfatase mRNA levels in breast malignancies and
      background tissues from 38 patients by reverse transcription and polymerase chain
      reaction. The levels in breast cancer tissues were significantly increased at
      1458.4+/-2119.7 attomoles/mg RNA (mean +/- SD) as compared with 535.6+/-663.4
      attomoles/mg RNA for non-malignant tissues (P<0.001). Thus, increased steroid
      sulfatase expression may be partly responsible for local overproduction of
      estrogen and provide a growth advantage for tumor cells.

PMID- 10925214
TI  - Steroid-inducible transcription of the 3beta/17beta-hydroxysteroid dehydrogenase
      gene (3beta/17beta-hsd) in Comamonas testosteroni.
AB  - The expression of the Comamonas testosteroni gene, encoding 3beta/17beta
      hydroxysteroid dehydrogenase enzyme (3beta/17beta-HSD), was analyzed at the
      transcriptional level. Northern blot analysis detected a 1 kb transcript in
      bacterial cells grown in minimum media supplemented with Casamino acids and
      testosterone. Also this transcript was observed when cells were grown in presence
      of 1-dehydrotestosterone, androstenedione and 1,4-androstadien-3, 17dione, but
      not in presence of acetate, citrate, cholic acid, cholesterol, and cortisol. In
      addition, this effect was dependent on the presence of another carbon source in
      the growth medium used, revealing catabolite repression.

PMID- 10925215
TI  - Altered corticosterone status impairs steroidogenesis in the granulosa and thecal
      cells of Wistar rats.
AB  - Hypo- and hyper-corticosteronisms have adverse effects on ovarian endocrine and
      exocrine functions. In the present study, the mechanism by which corticosterone
      in excess or insufficiency impairs steroidogenesis in granulosa and thecal cells
      was investigated in adult albino Wistar rats. In this regard, rats were
      administered with corticosterone-21-acetate (2 mg/100 g b.wt., s.c., twice daily)
      or metyrapone (11beta-hydroxylase blocker) (10 mg/100 g b.wt., s.c., twice daily)
      for 15 days and a group of corticosterone/metyrapone treated rats was withdrawn
      of treatment and maintained for another 15 days and killed during their diestrus
      phase. Administration of corticosterone-21-acetate while elevated the serum
      corticosterone levels, metyrapone diminished the same. Administration of
      metyrapone reduced the serum levels of LH and estradiol; corticosterone reduced
      the levels of FSH in addition to LH and estradiol. In vitro production of
      progesterone and estradiol by the granulosa and thecal cells was decreased due to
      altered corticosterone status. Whereas administration of corticosterone
      significantly reduced the activity of 3beta-hydroxysteroid dehydrogenases (3beta
      HSD) in granulosa and thecal cells, it reduced the activity of 17beta-HSD only in
      granulosa cells. While metyrapone treatment reduced the activity of 17beta-HSD in
      granulosa as well as thecal cells, it reduced the activity of 3beta-HSD only in
      thecal cells. The findings of the present investigation clearly demonstrate that
      excess or insufficiency in corticosterone affects steroidogenic process in the
      ovary. This is achieved by decreasing the levels of gonadotropins probably by
      their diminished synthesis and secretion and by interfering at the signal
      transduction process of these gonadotropins.

PMID- 10925216
TI  - Modulation of NADPH-diaphorase and glial fibrillary acidic protein by
      progesterone in astrocytes from normal and injured rat spinal cord.
AB  - Progesterone (P4) can be synthesized in both central and peripheral nervous
      system (PNS) and exerts trophic effects in the PNS. To study its potential
      effects in the spinal cord, we investigated P4 modulation (4 mg/kg/day for 3
      days) of two proteins responding to injury: NADPH-diaphorase, an enzyme with
      nitric oxide synthase activity, and glial fibrillary acidic protein (GFAP), a
      marker of astrocyte reactivity. The proteins were studied at three levels of the
      spinal cord from rats with total transection (TRX) at T10: above (T5 level),
      below (L1 level) and caudal to the lesion (L3 level). Equivalent regions were
      dissected in controls. The number and area of NADPH-diaphorase active or GFAP
      immunoreactive astrocytes/0.1 mm(2) in white matter (lateral funiculus) or gray
      matter (Lamina IX) was measured by computerized image analysis. In controls, P4
      increased the number of GFAP-immunoreactive astrocytes in gray and white matter
      at all levels of the spinal cord, while astrocyte area also increased in white
      matter throughout and in gray matter at the T5 region. In control rats P4 did not
      change NADPH-diaphorase activity. In rats with TRX and not receiving hormone, a
      general up-regulation of the number and area of GFAP-positive astrocytes was
      found at all levels of the spinal cord. In rats with TRX, P4 did not change the
      already high GFAP-expression. In the TRX group, instead, P4 increased the number
      and area of NADPH-diaphorase active astrocytes in white and gray matter
      immediately above and below, but not caudal to the lesion. Thus, the response of
      the two proteins to P4 was conditioned by environmental factors, in that NADPH
      diaphorase activity was hormonally modulated in astrocytes reacting to trauma,
      whereas up-regulation of GFAP by P4 was produced in resting astrocytes from non
      injured animals.

PMID- 10925218
TI  - 3D-structure of human estrogenic 17beta-HSD1: binding with various steroids.

PMID- 10925217
TI  - Progesterone effect on cell growth, ultrastructural aspect and estradiol
      receptors of normal human breast epithelial (HBE) cells in culture.
AB  - The stimulating effect of estradiol (E2) on breast cell growth is well
      documented. However, the actions of progesterone (P) and its derivatives remain
      controversial. Additional information is therefore necessary. On a culture system
      of normal human breast epithelial (HBE) cells, we observed an inhibitory effect
      on cell growth of a long-term P treatment (7 days) in the presence or absence of
      E2, using two methods: a daily cell count providing a histometric growth index,
      and [3H]-thymidine incorporation during the exponential phase of cell growth. A
      scanning electron microscopy study confirmed these results. Cells exhibited a
      proliferative appearance after E2 treatment, and returned to a quiescent
      appearance when P was added to E2. In both studies, P proved to be as efficient
      as the synthetic progestin R5020. Moreover, the immunocytochemical study of E2
      receptors indicated that E2 increases its own receptor level whereas P and R5020
      have the opposite effect, thus limiting the stimulatory effect of E2 on cell
      growth. In the HBE cell culture system and in long-term treatment, P and R5020
      appear predominantly to inhibit cell growth, both in the presence and absence of
      E2.

PMID- 10925219
TI  - Presentation of the International Nomenclature for Congenital Heart Surgery. The
      long way from nomenclature to collection of validated data at the EACTS.
AB  - An International Nomenclature for Congenital Heart Surgery was officially adopted
      at the Annual Meeting of the EACTS in Glasgow, UK on September 6, 1999. This
      nomenclature was achieved following 1 year's work of the International
      Nomenclature and Data Base Committee for Congenital Heart Surgery of the Society
      of Thoracic Surgeons. This international group included members from the STS,
      AATS, AHA and EACTS and associated surgeons and cardiologists from United States,
      Canada, Australia and Europe. The Nomenclature includes a minimal data set of 21
      items and lists of 150 diagnoses, 200 procedures, 32 complications and 28 extra
      cardiac anomalies and preoperative risk factors. It will serve as a basis for the
      Pediatric European Cardiac Surgical Registry (http://www.pediatric. ecsur.org).
      The outcome of such an International Nomenclature represents an important event
      for the medical community in charge of treating patients with congenital heart
      diseases. It will allow scientific exchanges on an international scale and
      promote multicenter evaluation of congenital heart surgery. Nevertheless, this
      Nomenclature is only the first step. Further collection of validated data at the
      Pediatric ECSUR Data Base requires ethical belief, time consumption and financial
      resources. Comparison of results, according to pathologies, across centers and
      countries will help define, in the future, official European standards of Quality
      of Care available for health care organizations, public scrutiny and governmental
      agencies.

PMID- 10925220
TI  - Surgical treatment of primary sarcoma of the lung.
AB  - OBJECTIVE: To study the results of surgical treatment of primary lung sarcoma.
      METHODS: Between 1982 and 1998, we performed 18 macroscopically complete
      resections for primary sarcomas of the lung. The records of all patients were
      reviewed, as were pathological slides. Presence of symptoms, tumour size (more or
      less than 5 cm), complete resection, TNM stage and histology grade were analyzed
      for predictors of survival. RESULTS: Patients comprised 11 women and seven men
      whose age ranged from 19 to 73 years (mean 50 years). Mean tumour diameter was
      8.05 cm (range 2.5-15 cm) There were one grade 1, eight grade 2 and nine grade 3
      tumours. Tumours in two patients were unresectable at first presentation, and
      another was of doubtful resectability according to computed tomography scan.
      These three patients received pre-operative chemotherapy, with a partial response
      in the two unresectable patients allowing macroscopically complete resection in
      both cases. We performed 12 lobectomies (extended to the chest wall in two cases
      and to the diaphragm in two cases) and six pneumonectomies (extended to the chest
      wall in one case and the superior vena cava in one case). Operative and 30 days
      post-operative mortality were nil. Resection margins were invaded in two cases.
      Six patients received post-operative chemo- or radiotherapy and three others
      underwent repeat resections for pulmonary sarcoma recurrence. No patients were
      lost to follow-up. Pulmonary sarcomas recurred in eight patients (44%) leading to
      death in five cases after a mean period of 17 months. Overall median survival was
      48 months, and actuarial 5-year survival 43%. Only TNM stage correlated with
      significantly increased survival. CONCLUSION: As complete resection is the best
      therapeutic option for obtaining an acceptable survival rate in primary pulmonary
      sarcoma, pre-operative chemotherapy can be a useful adjunct in increasing the
      resectability of these tumours.

PMID- 10925221
TI  - The long-term morbidity of pleuroperitoneal shunts in the management of recurrent
      malignant effusions.
AB  - OBJECTIVE: Over the last 15 years we have managed patients with malignant pleural
      effusion, using a single procedure with thoracoscopy and talc pleurodesis or
      shunt as appropriate. Talc pleurodesis remains our primary treatment option but
      in those patient shown to have the 'trapped lung syndrome', in whom pleurodesis
      would fail, we have been using a pleuroperitoneal shunt. METHODS: This
      retrospective review was undertaken to evaluate the mortality and morbidity of
      pleuroperitoneal shunts in the management of malignant pleural effusions and to
      assess their long-term results. Three hundred and sixty patients were treated for
      malignant effusions during the period 1983-1998, 160 (44.4%) of whom had a
      pleuroperitoneal shunt inserted. There were no intraoperative deaths and the
      hospital mortality was three patients (1.87%). Follow up was available for 88.1%
      of patients. The median survival of all malignant cases was 7.7 months (range 1
      72 months). Mesothelioma patients survived somewhat longer with a median survival
      of 10.1 months. RESULTS: Shunt complication occurred in 21 patients (14.8%).
      Twelve patients developed shunt occlusion, requiring revision in five and
      replacement in seven. The shunt was removed in eight patients due to skin erosion
      in one patient and infection in seven patients. The distal limb of shunt was
      broken in one patient and the shunt was replaced. One patient developed malignant
      seeding along the chest wall at the site of shunt insertion but there were no
      incidences of peritoneal deposits. Effective palliation was achieved in 95% of
      patients. CONCLUSIONS: Pleuroperitoneal shunt insertion provides effective and
      safe palliation for malignant pleural effusion when associated with the 'trapped
      lung syndrome'. There are however complications which require revision or shunt
      removal. There is no evidence that peritoneal deposits result from
      pleuroperitoneal shunting.

PMID- 10925222
TI  - Surgery for non-small cell lung cancer: postoperative survival based on the
      revised tumor-node-metastasis classification and its time trend.
AB  - OBJECTIVE: To clarify results of surgery for non-small cell lung cancer (NSCLC)
      based on the new tumor-node-metastasis (TNM) classification revised in 1997 and
      its time trend. METHODS: A total of 921 patients operated from 1980-1994 were
      retrospectively reviewed. For analysis of time trend, they were grouped into
      three periods by the year of operation (period (1): 1980-1984, period (2): 1985
      1989, and period (3): 1990-19-94). RESULTS: Concerning patients' characteristics,
      recent increase in the ratio of patients whose tumor was discovered at mass
      screening (31% in period (1), 40% in period (2), and 50% in period (3)), and
      increase in the ratio of p-stage IA patient (16, 20, and 29%, respectively) were
      marked. Decrease in the ratio of operation-related death and the ratio of
      exploratory thoracotomy was significant. Concerning level of operation, decrease
      in the ratio of pneumonectomy, increase in the ration of sublober resection and
      that of tracheal or bronchoplastic procedures were significant. Postoperative
      survival for all patients was significantly better in period (2) or (3) than that
      in period (1); no significant difference was demonstrated between period (2) and
      (3) (5-year survival rates: 35% for period (1), 56% for period (2), and 56% for
      period (3)). Stratified p-stage, improvement of postoperative survival in recent
      years was demonstrated in p-stage IIA, IIB, IIIA, and IIIB diseases. CONCLUSIONS:
      Postoperative survival for all NSCLC patients has been improved with significant
      increase of early-stage (p-stage IA) patients. Concerning level of resection,
      recent increase in patients who underwent sublobar resection and bronchoplastic
      procedures was marked.

PMID- 10925223
TI  - Long-term outcome after resection for bronchial carcinoid tumors.
AB  - OBJECTIVES: We sought to determine the long-term survival of patients treated for
      bronchial carcinoid tumors and whether lesser resections have had an effect on
      outcomes. METHODS: We conducted a retrospective, multi-institutional review of
      patients treated surgically for primary bronchial carcinoid tumors since 1980.
      Operative approach, pathologic stage, histology, surgical complications, tumor
      recurrence, and long-term survival were assessed. RESULTS: There were 50 men and
      89 women with a mean age of 52.2+/-17.4 and 58.9+/-13.3 years, respectively
      (P=0.021). Men were more likely to be current or former smokers than were women.
      Operations included lobectomy or bilobectomy in 110, pneumonectomy in four, wedge
      resection in 22, and bronchial sleeve resection only in three patients; resection
      was performed thoracoscopically in six patients. One patient died
      postoperatively. Stages were I, 121; II, nine; III, six; and IV, three. Typical
      carcinoid tumors were stage I in 100 and more advanced (stages II-IV) in nine,
      whereas atypical carcinoid tumors were stage I in 18 and more advanced in eight
      (P=0. 002). Median follow-up was 43 months (range 1-149) during which 21 (15%)
      patients died (four from recurrent cancer) and 19 patients (14%) were lost to
      follow-up. Recurrent cancer developed in 2/98 patients with typical and 5/25
      patients with atypical subtypes (P<0. 001; log-rank test). The likelihood of
      recurrence was related to histological subtype (relative risk 7.9 for atypical
      carcinoid; 95% confidence interval 1.4-43.5). Five-year survival was 88% for
      stage I patients and was 70% for patients with more advanced stages. When
      stratified by stage, survival was related to age (relative risk=1.9 for a 10 year
      increase in age; 95% confidence interval 1.2-2.9) and possibly to the
      histological subtype, but not to patient gender, year of operation, or type of
      operation performed. CONCLUSIONS: Either major lung resection or wedge resection
      is appropriate treatment for patients with early stage typical bronchial
      carcinoid tumors. Survival is favorable for early stage tumors regardless of
      histological subtype. Local recurrence is more common among patients with
      atypical subtypes, suggesting that a formal resection may improve long-term
      outcome.

PMID- 10925224
TI  - Single-clamp technique for aneurysms of the descending thoracic aorta: report of
      132 consecutive cases.
AB  - OBJECTIVE: To determine the efficacy of a single-clamp technique in preventing
      spinal cord ischemia during repair of aneurysms of the descending thoracic aorta.
      PATIENTS AND METHODS: From January 1989 to May 1999, 132 consecutive patients (91
      men and 41 women, aged 31-86 years), with aneurysms of the descending thoracic
      aorta underwent repair using a single-clamp technique and temporary partial
      distal exsanguination. The diseased aortic segment was replaced with a Dacron
      graft. Blood was re-infused from an auto-transfusion device, and the segmental
      vessels were over-sewn but not implanted into the graft. RESULTS: The average
      aortic cross-clamp time was 26.4 min (range, 11-67 min) for the overall group and
      37.4 min for patients who had spinal cord complications. An average of 2066 ml of
      blood was auto-transfused (range, 450-6100 ml). During the first 30 postoperative
      days, 17 patients (12.9 %) died. Eleven patients (8.3%) had spinal cord
      dysfunction, six patients (4.5%) had lower-extremity paraparesis, and five
      patients (3.8%) had paraplegia. Nine patients (6.8%) had renal failure
      necessitating hemodialysis. Other complications included bleeding in 15 cases
      (11.4%), respiratory failure in 12 cases (9.1%), wound-related sequelae in five
      cases (3.8%), distal embolism in five cases (3.8%), and bowel ischemia in two
      cases (1.5%). CONCLUSION: The single-clamp technique yielded an acceptable
      complication rate, and the mortality was comparable to that seen after the use of
      more complex methods. For satisfactory results, the cross-clamp time should not
      exceed 30 min.

PMID- 10925225
TI  - Eight years clinical experience with the replacement of the ascending aorta using
      composite xenopericardial conduit.
AB  - OBJECTIVE: The evaluation of early and late results after ascending aorta
      replacement with composite glutaraldehyde-treated xenopericardial valved conduit.
      METHODS: From December 1989 to May 1999 the ascending aorta was replaced with 148
      composite xenopericardial conduits aorta in 145 patients. Biological valves were
      inserted in 28 conduits, mechanical valves - in 116. The age of 40 female (28%)
      and 105 male (72%) patients ranged from 10 to 60 years (mean, 38.7+/-12 years).
      The original diseases were: atherosclerosis in 51 (35%), cystic media necrosis in
      50 (35%), Marfan syndrome in 35 (24%), syphilis in three (2%), non-specific
      aortitis in one (0.7%), Turner syndrome in one and infective endocarditis in four
      cases. Aortic dissection was found in 67 patients (46%): type I in 14 (23%) and
      type II in 53 (77%). Twenty-one patients (15%) were operated on during the acute
      phase of the dissection. The Bentall-DeBono technique was used in 144 operations,
      in four cases (2.7%) supracoronary resection was performed. Associated procedures
      included: mitral valve repair (five), CABG (four), resection of the coarctation
      (two), MV replacement (two). Biological tissues condition was assessed using TTE
      TEE and computed tomography (CT) scanning technique. RESULTS: Hospital mortality
      was 8.3 % (12 patients). The death was caused by: low cardiac output (three),
      arrhythmia (two), neurological complications (one), sepsis (one), polyorgan
      failure (four), bleeding (one). Non-lethal complications included: bleeding
      (four), heart failure (two), persisting A-V block (two), polyorgan failure
      (three), cerebral (two), mediastinitis (three), and early prosthetic endocarditis
      in three patients. All three patients with endocarditis were successfully re
      operated and conduit replaced with the same type of the device. Late follow-up
      ranged from 2 months to 8 years (mean, 51 months) and complete in 87% of the
      discharged patients (115 patients). There were four valve-related deaths due to
      thrombembolia and five deaths non related to the valve and/or conduit. Clinical
      and instrumental evaluation did not reveal any signs of tissue degeneration at
      the conduit and biovalves' cusps. CONCLUSIONS: The xenopericardial valved conduit
      is an effective and acceptable device for the replacement of ascending aorta in
      almost all cases, it provides good early and late results. It's pliability and
      elasticity are especially attractive in situations with frail tissues and high
      risk of bleeding.

PMID- 10925226
TI  - Ischemic spinal cord injury induced by aortic cross-clamping: prevention by
      riluzole.
AB  - OBJECTIVE: Recent studies confirmed the deleterious role of glutamate in the
      pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We
      investigated the effect of riluzole, an anti-glutamate drug, in a rat model of
      spinal cord ischemia. MATERIALS AND METHODS: Spinal cord ischemia was induced in
      normothermia for 14 min in Sprague-Dawley rats using direct aortic arch plus left
      subclavian artery cross-clamping through a limited thoracotomy. Experimental
      groups were as follows: sham-operation (n=15), control (n=15) receiving only
      vehicle, riluzole (n=15) receiving riluzole (4 mg/kg) before clamping and at the
      onset of reperfusion. Separate animals were used for monitoring physiologic
      parameters in the sham-operation (n=3), control (n=5), and riluzole (n=5) groups.
      Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were
      randomly killed at 24, 48, or 96 h (n=5 for each time). Spinal cords were
      harvested for histopathology, immunohistochemistry for microtubule-associated
      protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose
      gel electrophoresis. RESULTS: All sham-operated rats had a normal neurologic
      outcome, whereas all control rats suffered severe and definitive paraplegia.
      Riluzole-treated rats had significantly better neurologic function compared to
      the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray
      matter of control rats, whereas riluzole-treated rats suffered usually mild to
      moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2
      immunoreactivity was completely lost in control rats, whereas it was preserved
      either completely or partly in riluzole-treated rats. TUNEL staining revealed
      numerous apoptotic neurons scattered within the whole gray matter of control
      rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in
      treated rats. DNA extracted from lumbar spinal cords of sham-operated and
      riluzole-treated rats exhibited no laddering, whereas spinal cords from control
      rats showed DNA laddering with fragmentation into approximately 180 multiples of
      base pairs. CONCLUSIONS: Riluzole may protect the spinal cord in a setting of
      severe ischemia by preventing neuronal necrosis and apoptosis. This drug may
      therefore be considered for clinical use during 'high risk' surgical procedures
      on the thoracoabdominal aorta.

PMID- 10925227
TI  - Endocardial and epicardial radiofrequency ablation in the treatment of atrial
      fibrillation with a new intra-operative device.
AB  - OBJECTIVE: Atrial fibrillation has been a difficult problem to solve in many
      surgical patients, especially in those with mitral valve pathology. This study
      evaluates the results of endocardial and epicardial radiofrequency ablation with
      a new intra-operative device in the treatment of atrial fibrillation. METHODS: We
      operated on 65 patients with atrial fibrillation, 58 of which had concomitant
      mitral surgery. Atrial fibrillation was chronic (over 1 year) in 46 patients
      (group A) and paroxysmal or recent onset in 12 (group B). Group C had lone atrial
      fibrillation (two), concomitant coronary artery disease (four) or a sarcoma
      (one). Bilateral pulmonary vein isolation with a new intra-operative device was
      performed through multiple dry lesions in all patients. Groups A and B had
      endocardial applications at 70 degrees C during 60 s and group C had epicardial
      applications at 75 degrees C. Three group C patients had epicardial applications
      off pump. Atrial wall biopsies were performed in nine patients from groups A and
      B. RESULTS: There were no serious post-operative complications. At 1 month follow
      up 54% of all patients were out of atrial fibrillation and 34% were in normal
      sinus rhythm with bilateral atrial contraction (Santa Crus Score 4). At 6 months
      follow-up, in spite of some crossover of patients among groups, similar results
      were obtained. The success of the procedure was 69% (Santa Crus scores 3 and 4)
      in mitral patients with a left atrial volume smaller than 200 cm(3). Preliminary
      data on the transmurality of the lesions is presented. The patients submitted to
      epicardial radiofrequency ablation (group C) have satisfactory results at 1 month
      (six out of seven were out of AF). CONCLUSIONS: Both endocardial and epicardial
      RF applications are simple and quick to perform and do not pose an additional
      risk for most patients. Furthermore we believe that it is possible to perform
      bilateral epicardial radiofrequency ablation of the pulmonary veins without
      cardiopulmonary bypass. Further refinements of the technique are needed to assure
      transmurality of all lesions and better results.

PMID- 10925228
TI  - Significance of right bundle branch block in the diagnosis of myocardial ischemia
      in patients undergoing coronary artery bypass grafting.
AB  - BACKGROUND: Perioperative diagnosis of myocardial ischemia following cardiac
      surgical procedures remains a challenging problem. Particularly, the role of new
      conduction disturbances as markers of postoperative ischemia is still
      questionable. The goal of this study was to elucidate the diagnostic significance
      of new postoperative right bundle branch block (RBBB) for the detection of
      perioperative myocardial ischemia in patients undergoing elective coronary artery
      bypass grafting (CABG). METHODS: In 169 consecutive patients, three-channel
      Holter monitoring and serial assessment of serum enzymes were performed for 48 h,
      and 12-lead ECG repeated for up to 5 days postoperatively. Postoperative events
      were classified as either myocardial infarction (MI), transient ischemic events
      (TIE) or various conduction disturbances. RESULTS: Transient (n=9) or permanent
      (n=4) RBBB occurred in 13 patients (8%); 14 patients (8%) showed signs of
      perioperative MI and 18 patients (11%) evidence of TIE. Peak activity of creatine
      kinase (CK, 561+/-135 vs. 316+/-19, P<0.05) and CK-MB (22.7+/-3.2 vs. 13.4+/-0.8,
      P<0.01) were higher in patients with RBBB than in patients without perioperative
      ischemic events. Peak CK-MB levels were significantly higher in patients with MI
      as compared to those with RBBB (33.4+/-7.6 vs. 22.7+/-3.2, P<0. 05). Patients
      with TIE had similar perioperative enzyme levels as patients with no events.
      CONCLUSION: It is concluded that the combined assessment of repeated 12-lead ECG,
      continuous Holter monitoring and enzyme analysis allows a reliable diagnosis of
      perioperative myocardial ischemia and conduction disturbances. The occurrence of
      new RBBB following elective CABG is indicative of perioperative myocardial
      necrosis and thus serves as a valuable tool for the diagnosis of new,
      perioperative ischemic events.

PMID- 10925229
TI  - Post infarction ventricular septal defect - can we do better?
AB  - OBJECTIVE: To identify predictors of early and late outcome among 117 consecutive
      patients who underwent postinfarction ventricular septal defect (VSD) repair over
      a period of 12 years. METHODS: A retrospective analysis of clinical data was
      performed. Mean age was 65.5+/-7.8. There were 43 females. Full data were
      obtained in 110 patients. Of these, 76 patients presented with anterior and 34
      with posterior VSD. Thirty-three patients were operated in cardiogenic shock.
      Mean time between myocardial infarction (MI) and VSD development was 5.6+/-7.8
      days (median 4) and from VSD to surgery 9. 0+/-28.1 (median 2). Sixty-six
      patients had intraaortic balloon pump (IABP) inserted, and 15 were ventilated
      preoperatively. Logistic regression and Cox regression were used for multivariate
      analysis. RESULTS: Thirty days mortality was 37%. Among 110 patients, in whom
      complete analysis was possible, 38 died within 30 days (35%). Mortality in the
      posterior VSD group was 35% and in the anterior VSD group 34% (NS). In 44
      patients (40%) a residual shunt was found on postoperative echocardiography. This
      required reoperation in 13 patients (four deaths). Cardiogenic shock prior to
      surgery adversely influenced early survival - odds ratio (OR) 5.7 (confidence
      interval (CI) 2.1-16.0) (P=0.0008). Deterioration of haemodynamic status in
      between admission and surgery was stronger predictor of mortality than shock on
      admission - OR 6.0 (CI 1.6-22.6) (P=0.008) vs. 3.1 (CI 1.0-9.3) (P=0.049). A
      longer time between MI and surgery favoured survival - OR 0.1 (CI 0.03-0.4)
      (P=0.002). The time period from the infarct to the septal rupture, but not from
      the rupture to surgery, appeared to be a significant predictor of survival - OR
      0.2 (CI 0. 05-0.6) (P=0.008). Five years survival was 46+/-5%. Preoperative
      cardiogenic shock affected late survival - OR 2.7 (CI 1.5-4.9) (P=0. 001). Of 72
      patients who survived 30 postoperative days, 12 (17%) were in New York Heart
      Association (NYHA) class III or IV and five (6.9%) in Canadian Cardiovascular
      Soceity (CCS) class III or IV at the last follow-up. CONCLUSIONS: Preoperative
      cardiogenic shock and early postinfarction septal rupture carry a grave
      prognosis. Achieving haemodynamic stability prior to surgery may be beneficial
      but prolonged attempts to improve patients' cardiovascular state are hazardous.

PMID- 10925230
TI  - Factors influencing early outcome of Norwood procedure for hypoplastic left heart
      syndrome.
AB  - OBJECTIVE: [corrected] The operative outcome of the Norwood procedure for
      hypoplastic left heart syndrome is still not satisfactory. Conflicting reports
      concern factors associated with early Norwood procedure mortality and the reasons
      for the instability after surgery are not sufficiently understood. The purpose of
      this study was to determine some perioperative factors influencing early (30
      days) outcome. METHODS: We retrospectively analyzed a group of 30 consecutive
      children with hypoplastic left heart syndrome (aged 5-39 days) who underwent
      Norwood procedure in 1997 and 1998. The following factors were considered and
      statistically analyzed: operative age, birth weight, operative weight, serum
      level of bilirubin, aminotransferases, creatinine, urea, arterial blood gasses,
      anatomic subgroups, ascending aorta and arch size, systemic to pulmonary modified
      right Blalock-Taussig shunt size, cardiopulmonary circulatory arrest time,
      cardiopulmonary bypass time, and delayed chest closure. Eighteen patients
      underwent hemi-Fontan procedure with one late death and the modified Fontan
      operation was performed in 16 of them (one late death). RESULTS: The early
      mortality was 37%. Seven deaths (64%) occurred during the first 24 h after
      operation. There was a significant difference between survivals and non-survivals
      in: birth weight (P=0.047), operative age (P=0.016), preoperative serum level of
      bilirubin (P=0.044), and cardiopulmonary circulatory arrest time (P=0.006). The
      other assessed factors were not found to be predictors of early mortality. All 16
      survivals followed up are in New York Heart Association class I or II.
      CONCLUSIONS: Anatomic and functional status of the patient, as well as procedural
      factors are related to Norwood operation early mortality. High mortality in
      hypoplastic left heart syndrome after stage I surgery indicates the necessity of
      assessing all factors which may determine further improvement in the outcome.

PMID- 10925231
TI  - Influence of coronary anatomy and reimplantation on the long-term outcome of the
      arterial switch.
AB  - BACKGROUND: Abnormal coronary artery anatomy is reported to have a significant
      influence on the outcome of the arterial switch operation. This study examines
      the impact of coronary anatomy and the occurrence of late coronary obstruction on
      left ventricular (LV) function and long-term outcome. METHODS: Coronary artery
      anatomy, of 170 patients after arterial switch operation (1977-1999), was
      determined based on operative reports and pre-operative aortograms. Current
      status was evaluated using ECGs, echocardiograms, scintigraphy, and post
      operative coronary angiograms. RESULTS: In 133/170 patients, coronary artery
      anatomy consisted of an anterior descending (LAD) and circumflex artery (Cx) from
      the left sinus and the right coronary artery (RCA) from the right or posterior
      sinus. The left coronary had an intramural initial course in two of these
      patients. Fifteen patients had the LAD from the left and Cx and RCA from the
      right sinus; eight had LAD and RCA from one sinus and Cx from the other; four had
      single ostium; and three had three separate ostia. Four patients had complex
      patterns and four patients had a supra commissural coronary. To date, follow-up
      angiography was performed in 59 patients. Surgical coronary sequellae were found
      in five patients. Two patients had an occluded left ostium. Initially, they were
      asymptomatic but showed polymorphic ventricular extrasystoles on ECG and moderate
      LV dysfunction with large irreversible perfusion defects on scintigraphy. Both
      patients developed ventricular fibrillation at the age of 14 years. One patient
      did not survive. The other patient required implantation of a defibrillator. One
      patient has an occluded RCA, one patient has stenosis of the right ostium and one
      patient has multiple tortuous collaterals without obstruction of a major branch.
      In the latter three patients, coronary sequellae were not suspected on ECG, echo,
      or scintigraphy and were only found on follow-up angiography. Retrograde
      collateral flow was noted in all three occluded coronaries. LV dysfunction, with
      normal coronaries, was noted in three patients. All, of these patients, had peri
      operative ischaemia suggesting failure of myocardial protection. Two are now
      asymptomatic with mild LV dysfunction. One patient continues to have severe
      myocardial dysfunction and secondary aortic insufficiency. A Ross-like procedure
      was performed placing the original aortic valve in the neo-aortic root. Coronary
      artery anatomy did not influence early survival or late coronary sequellae.
      CONCLUSION: Abnormal coronary anatomy was not a determinant of outcome in our
      study. Surgical coronary obstruction is independent of original anatomy. It can
      be almost silent and is potentially fatal. Follow-up angiography must be
      considered in all patients after the arterial switch operation.

PMID- 10925232
TI  - Results of modified Norwood's operation for hypoplastic left heart syndrome.
AB  - OBJECTIVE: The aim of the study was to analyze intermediate results of treatment
      of the hypoplastic left heart syndrome based on selective indication criteria.
      METHODS: Between February 1997 and May 1999 38 patients with hypoplastic left
      heart syndrome (n=35), or with functional variant of hypoplastic left heart
      syndrome (n=3) were admitted to our department. Contraindications for surgery
      were birth weight <2500 g, diameter of ascending aorta <2 mm, severe tricuspid
      regurgitation persisting after initial stabilization, pulmonary regurgitation
      more than mild, dysfunction of the systemic right ventricle and failure to
      effectively resuscitate circulation before surgery. RESULTS: Based on these
      criteria surgery was not indicated in 17 patients. Twenty-one infants were
      operated on by modified Norwood's procedure using only autologous great vessel
      tissue for reconstruction of systemic outflow. Overall hospital mortality was 14%
      (three patients). Eighteen survivors (86%) were discharged with well-balanced
      circulation. There was one late death (5%). Thirteen patients had already
      undergone the second stage (bi-directional Glenn) with no death. The mean follow
      up was 13. 2+/-9.1 months (range 4-32 months). Considering both early and late
      events the probability of survival for the whole group (n=21) from the time of
      surgery was 86% at 1 month, 80% at 12 months, and it remained unchanged at 18 and
      24 months of follow-up. CONCLUSIONS: Only a limited number of European countries
      offer surgical treatment of hypoplastic left heart syndrome. Promising
      intermediate results (80% survival rate after stage I and II) achieved at our
      department do not only reflect overcoming the learning curve but also a selective
      approach to indication for surgery as well. In a country with limited resources
      selective approach to the patients with hypoplastic left heart syndrome is
      justified.

PMID- 10925233
TI  - Long-term mechanical circulatory support with the wearable Novacor left
      ventricular assist system.
AB  - OBJECTIVE: As of July 1st 1999, 36 European patients have lived for more than 1
      year supported by the Novacor wearable electric left ventricular assist system
      (LVAS). All were unresponsive to maximum medical therapy, prior to implantation.
      These patients offer an unique opportunity to evaluate the feasibility of long
      term ambulatory mechanical circulatory support as a therapeutic option for
      patients in profound cardiac failure. METHODS: Data was obtained from the Novacor
      European Registry. RESULTS: At the time of implantation, median age was 55 (18
      67) years. Aetiology was ischemic (9, 25%) or idiopathic (26, 72%)
      cardiomyopathy, and myocarditis (1, 3%). Median duration of LVAS support was 1.49
      (1. 03-4.10) years. Eight recipients had LVAS support times >2 years, of which
      two were >3 years and one >4 years. The median time spent outside the hospital
      was 1.27 (0.58-3.83) years, representing 82% of the duration of LVAS support. No
      mechanical failure was observed during the entire observation period. One pump
      was replaced electively after 3.67 years due to pump driver wear-out. Twelve
      patients (33%) are currently on support while 17 were transplanted (14, 39%) or
      weaned (3, 8%). Seven (19%) patients died after a median of 1.24 years
      circulatory support. CONCLUSIONS: Experience with long-term Novacor LVAS
      recipients has demonstrated effective rehabilitation in this group of patients
      with refractory advanced heart failure. This suggests that LVAS therapy may offer
      a safe and realistic option for patients for whom no other effective therapy is
      available. The patient sub-population that would benefit most from this therapy
      remains to be defined.

PMID- 10925234
TI  - Disruption of the silver and non-silver coated sewing cuff of a new generation
      bileaflet valve prosthesis during aortic valve replacement: report on four cases.
AB  - OBJECTIVES: New generation bileaflet valve prostheses with a silver-coated sewing
      cuff like the St Jude Medical (SJM((R)) Regent) model are designed to offer a
      larger valvular orifice as well as a better resistance to postoperative
      prosthetic endocarditis, at the expense of a smaller sewing cuff. METHODS AND
      RESULTS: We report on four cases of aortic valve replacement where during the
      implantation procedure the fixation cuff disrupted, leading to the exchange of
      all four valve prostheses. This happened three times with silver- coated sewing
      cuffs and after withdrawal of the silver- coated cuff prostheses from the market,
      once with a non silver- coated sewing cuff. This was due to the arbitrary cutting
      of the cuff fixation suture at the ventricular side of the prosthesis, although
      the implantation was performed according to the recommendations of the company.
      This problem didn't occur previously, using other models of the same
      manufacturer, although the sewing cuff had been fixed in the same technique.
      CONCLUSION: Fixation of smaller sewing cuffs of mechanical valve prostheses with
      a critically exposed fixation suture at the ventricular side of the prosthesis
      represents a significant risk for disruption during the implantation process
      through cut off by chance. We recommend meticulous inspection of the sewing cuff
      for signs of disruption before seating the valve into position. During follow-up
      particular attention should be paid to valve dislodgement and leakage. The
      company was informed and advised by us to modify the fixation of the prosthetic
      annulus of the SJM((R)) Regent valve, which has led to an alternative cuff
      design, called the SJM Flex cuff.

PMID- 10925235
TI  - Cannulation of the cardiac lymphatic system in swine.
AB  - OBJECTIVE: Cardiac lymph is the most direct medium for analyzing metabological
      changes in the myocardial cell. Currently, dogs are the animals used for
      investigation of myocardial lymphatic function. However, questions arise when
      comparing and interpreting the human system to the experimental model, since the
      dog coronary anatomy is different from human anatomy and pulmonary lymph
      contamination is found in up to 81% of the cases. Swine, having similar coronary
      anatomy to humans, are a proven model for cardiovascular research. The purpose of
      this study was to investigate the cardiac lymphatic anatomy of the swine and to
      develop a reliable cannulation technique to collect the lymph. METHODS AND
      RESULTS: The lymphatic anatomy of 60 pigs was studied and classified and a new
      technique for lymphatic cannulation was developed. The cannulation success rate
      was 55%. In addition, no pulmonary lymph contamination was found at the
      cannulation site. CONCLUSION: We conclude that porcine myocardial lymphatics can
      be successfully cannulated for the investigation of myocardial lymphatic
      function.

PMID- 10925236
TI  - Improved myocardial preservation with short hyperthermia prior to cold
      cardioplegic ischemia in immature rabbit hearts.
AB  - OBJECTIVE: Recent observations have been shown that the induction and
      accumulation of heat shock proteins (HSPs) by short exposure to nonlethal whole
      body hyperthermia with normothermic recovery are closely associated with
      transient resistance to subsequent ischemia-reperfusion challanges. Here, this
      study was performed to investigate whether a shortly heat shock pretreatment
      affects the left ventricular (LV) function after cold cardioplegic ischemia in
      reperfused neonatal rabbit hearts. METHODS: Hearts from neonatal New Zealand
      White rabbits were isolated perfused (working heart preparation) and exposed to 2
      h of cold cardioplegic ischemia followed by reperfusion for 60 min. To induce the
      heat shock response neonatal rabbits (n=5, HT-group) were subjected to whole-body
      hyperthermia at 42.0-42.5 degrees C for 15 min, followed by a normothermic
      recovery period of 60 min, before harvesting and the onset of global hypothermic
      cardioplegic arrest. Another set of hearts (n=5, control group) without a heat
      treatment underwent a similar perfusion and ischemia protocol served as control.
      The postischemic recovery was assessed by measuring several parameters of LV
      function. LV biopsies from all control and heat treated animals were taken before
      ischemia and at the end of reperfusion to examine myocardial HSP levels by
      Western blot analysis. RESULTS: At 60 min of reperfusion the HT-group showed
      significant better recovery of ventricular function such as LV developed pressure
      (DP) (74.6+/-10 vs. 52.1+/-8.5%, P<0.05), LV positive dP/dt (910+/-170 vs. 530+/
      58 mmHg/s, P<0.01) and LV end-diastolic pressure (LVEDP) (8+/-2 vs. 18.4+/-5
      mmHg, P<0.05) than control. Myocardial oxygen consumption (MVO(2)) was
      significantly higher in the HT-group compared with control (0.054+/-0.006 vs.
      0.041+/-0.002 ml/g per min, P<0.05). Significant postreperfusion lower level in
      lactate production was observed in the HT-group (0.83+/-0.11 vs. 1.67+/-0.8
      mmol/l, P<0.05). Also, the recovery of hemodynamic parameters such as aortic
      flow, coronary flow and cardiac output was significantly superior (P<0.05) in the
      HT-group. Furthermore, high expression of HSP72(+)/73(+) were detected in the
      myocardial tissue samples of heat-treated rabbits by immunoblotting, appearing
      even at 60 min of normothermic recovery after heat stress. CONCLUSIONS: These
      data in the immature rabbit heart indicate that previous shortly heat treatment
      with high level expression of heat shock proteins (HSP72(+)/73(+)) before
      hypothermic cardioplegic ischemia provides transient tolerance against myocardial
      injury and could be an improvement for the postischemic functional recovery of
      neonatal hearts.

PMID- 10925237
TI  - The action of diaspirin cross-linked haemoglobin blood substitute on human
      arterial bypass conduits.
AB  - BACKGROUND: Immediately available blood substitutes could transform medicine. In
      coronary artery surgery, vasoconstriction induced by some of these agents could
      have serious implications. We have examined some of the vasoactive effects of one
      of these blood substitute, diaspirin cross-linked haemoglobin (DCLHb), on
      isolated rings of human arterial conduits. METHODS: Sections of human left
      internal mammary artery (LIMA) and radial artery (RA) were cut into 3-mm rings,
      mounted in individual organ baths containing aerated (95% O(2)/5% CO(2)) Krebs
      Heinseleit solution at 37 degrees C and attached to isometric strain gauge for
      measurements of tension. All rings were tested for the presence of endothelium by
      addition of carbachol to rings pre-contracted with phenylephrine. The relative
      importance of nitric oxide (NO) in contraction mediated by the addition of DCLHb
      was studied. RESULTS: Carbachol relaxed phenylephrine precontracted LIMA by
      72.3+/-1.7% and RA by 97+/-0.7% confirming the presence of a functional
      endothelium. Sodium nitroprusside (SNP) caused complete relaxation of LIMA with
      an EC(50) value of 2.0+/-0.1x10(-8) M and RA with an EC(50) value of 1. 9+/
      0.1x10(8) M. In the presence of DCLHb (10(-7) M), carbachol-induced relaxation
      was significantly reduced to 46.3+/-0. 7% (P<0.01) and the BC(50) value for SNP
      relaxation increased to 1. 2+/-0.1x10(-7) M (P<0.01). DCLHb caused rings to
      contract in the absence of phenylephrine with EC(50) values of 1.6+/-0.1x10(-7) M
      (LIMA) and 1.8+/-0.1x10(-7) M (RA). Presence of L-NAME (300 microM) caused no
      alteration in DCLHb-induced contraction. CONCLUSION: In this study of isolated
      rings of human vessels, DCLHb causes a significant reduction in relaxation
      mediated by carbachol and SNP, which is likely to be due to its ability to bind
      NO. However, it is possible that other mechanisms might contribute to the
      vasoconstrictor effects of DCLHb and these might be amenable to anti-vasospastic
      strategies.

PMID- 10925238
TI  - A novel modification of elephant trunk technique using a single four-branched
      arch graft for extensive thoracic aortic aneurysm.
AB  - Surgical repair for the extensive thoracic aortic aneurysm remains
      unsatisfactory, especially in elderly patients. We developed a total arch
      replacement with modified elephant trunk technique under moderately hypothermic
      cardiopulmonary bypass and selective brain perfusion, in which a 4-branched arch
      graft with a sewing 'collar' enabled the distal anastomosis just proximal to the
      innominate artery with open distal method and a long 'elephant trunk' was
      inserted into the descending aorta by the forceps catheter via the femoral
      artery. This modification is easy and less invasive, and reduces the risk of
      postoperative complications.

PMID- 10925239
TI  - Aortic valve replacement for the calcified ascending aorta in homozygous familial
      hypercholesterolemia.
AB  - A 72-year-old woman who had been diagnosed as homozygous familial
      hypercholesterolemia was admitted for chest discomfort. Computed tomography and
      cardiac catheterization revealed severe calcification of the aortic root and a
      high grade stenosis of the proximal right coronary artery. Aortic valve
      replacement concomitant with coronary artery bypass was done using temporary
      hypothermic circulatory arrest. This is preferred method when dealing the
      calcified aorta.

PMID- 10925240
TI  - Coexistent true and false left ventricular aneurysms.

PMID- 10925241
TI  - Can we produce a human corneal equivalent by tissue engineering?
AB  - Tissue engineering is progressing rapidly. Bioengineered substitutes are already
      available for experimental applications and some clinical purposes such as skin
      replacement. This review focuses on the development of reconstructed human cornea
      in vitro by tissue engineering. Key elements to consider in the corneal
      reconstruction, such as the source for epithelial cells and keratocytes, are
      discussed and the various steps of production are presented. Since one
      application of this human model is to obtain a better understanding of corneal
      wound healing, the mechanisms of this phenomenon as well as the function played
      both by membrane-bound integrins and components from the extracellular matrix
      have also been addressed. The analysis of integrins by immunohistofluorescence
      labelling of our reconstructed human cornea revealed that beta(1), alpha(3),
      alpha(5), and alpha(6) integrin subunits were expressed but alpha(4) was not.
      Laminin, type VII collagen and fibronectin were also detected. Finally, the
      future challenges of corneal reconstruction by tissue engineering are discussed
      and the tremendous applications of such tissue produced in vitro for experimental
      as well as clinical purposes are considered.

PMID- 10925242
TI  - A model of retinal cell differentiation in the chick embryo.
AB  - This article presents an overview of retinal cell differentiation in the chick
      embryo, in the context of a hypothetical model based on information generated
      during the last several years. The model proposes that: (1) most (if not all)
      proliferating neuroepithelial cells have the potential to give rise to a progeny
      comprising two or more different cell types; (2) the time at which cells undergo
      their terminal mitosis does not determine their differentiated fate; (3) many
      postmitotic precursor cells remain plastic (i.e., uncommitted) for some time
      after terminal mitosis, during which they encounter position-dependent signals as
      they migrate toward their definitive laminar position within the retina; (4) as a
      consequence of these inductive stimuli, precursor cells that migrate to different
      retinal layers express different transcriptional regulators; (5) morphologically
      undifferentiated precursor cells are committed to cell type-specific, complex
      patterns of differentiation, which they can express even when isolated from their
      normal microenvironment, and (6) even after precursor cells become committed to a
      specific identity, additional inductive signals are necessary for the cells to
      complete the development of a fully mature phenotype. The article presents a
      summary of the supportive evidence, as well as a critical evaluation of the
      model, and concludes with an overview of unanswered questions regarding retinal
      cell differentiation and a brief evaluation of the prospects for further progress
      in this field.

PMID- 10925243
TI  - Axonal regeneration of retinal ganglion cells: effect of trophic factors.
AB  - A variety of neurotrophic factors can influence the cell functions of the
      developing, mature and injured retinal ganglion cells. The discovery that retinal
      ganglion cell loss can be alleviated by neurotrophic factors has generated a
      great deal of interest in the therapeutic potential of these molecules. Recently,
      evidence has provided valuable information on the receptors that mediate these
      events and the intracellular signaling cascades after the binding of these
      ligands. Signaling by neurotrophic factors does not seem to restrict to
      retrograde messenger from the target but also includes local interactions with
      neighbouring cells along the axonal pathways, anterograde signaling from the
      afferents and autocrine signaling. More insight into the mechanisms of action of
      neurotrophic factors and the signal transduction pathway leading to the
      protection and regeneration of retinal ganglion cells may allow the design of new
      therapeutic strategies.

PMID- 10925244
TI  - Restoration of the retinofugal pathway.
AB  - In a relatively short period of time covering the last 2 decades, regeneration of
      retinofugal axons has become one of most prominent experimental models in
      restorative neurobiology. There is now a significant knowledge both on the
      mechanisms governing retinal ganglion cell responses to transection of the optic
      nerve, and the subsequent cell-cell interactions accumulating in death of the
      neurons. In addition, retinofugal axons served as an excellent model to examine
      whether, and to conclude that these axons have remarkable abilities for re
      growth. This last issue was of invaluable importance, because axons could
      regenerate in vivo, into peripheral nerve grafts, and last but not least within
      the white matter of the cut optic nerve. As it stands to date, the extremely
      complex aspects of axonal regeneration will probably be understood within the
      retinofugal pathway. Final elucidation of this delicate system will essentially
      lead to some revision of our knowledge concerning neurotraumatology and CNS
      repair.

PMID- 10925246
TI  - Primate retina: cell types, circuits and colour opponency by D.M. Dacey. Progress
      In retinal eye research 18 (1999), 737-763

PMID- 10925245
TI  - Assessing retinal function with the multifocal technique.
AB  - With the multifocal technique, as developed by Erich Sutter and colleagues,
      scores of focal electroretinogram (ERG) responses can be obtained in a matter of
      minutes. Although this technique is relatively new, it has already provided
      insights into the mechanisms of retinal disease. However, because it is new,
      there also remain questions about how it works and what it measures. This chapter
      considers some of these insights and some of these questions. The first part
      (Section 2) describes how the multifocal ERG (mERG) is recorded and considers its
      relationship to the full-field ERG. The mERG responses are shown to be from
      relatively local regions of the retina and are comprised of the same components
      as the full-field ERG. The diagnostic advantage of the mERG as compared to the
      full-field ERG is also illustrated. In Section 3, the effects of damage to
      different cell layers of the retina are shown to affect the mERG differently, and
      these changes are summarized within a conceptual framework. It is argued, for
      example, that when diseases of the receptor outer segment, like retinitis
      pigmentosa, result in small, depressed mERG responses, then the damage is, as
      expected, at the outer segment. However, when these diseases result in mERG
      responses that are reasonably large but very delayed, then the damage is beyond
      the outer segment, probably in the outer plexiform layer. The implicit time of
      the mERG, not amplitude, is the more sensitive measure of damage in degenerative
      diseases of the receptors. On the other hand, diseases, like glaucoma, which act
      on the ganglion axon, do not result in easily identified changes to the mERG
      unless inner retinal damage is involved as well. Inner retinal damage changes the
      waveform of the mERG and decreases the naso-temporal variation normally observed.
      Finally, diseases, like diabetes, that act on more than one layer of the retina
      can have a range of effects. In Section 4, recent work with the monkey mERG is
      reviewed, with emphasis on the relevance to human diseases. For example, blocking
      the sodium-based action potentials produced by ganglion and amacrine cells
      eliminates the naso-temporal variation in the monkey mERG and these altered mERG
      responses resemble those from some patients with diabetes or glaucoma. Finally,
      in Section 5 the second-order kernel is described. The presence of a second-order
      kernel has important implications for understanding the shape of the mERG
      response (first-order kernel). Full-field simulations of the mERG paradigm
      illustrate that the first-order kernel is comprised of responses with different
      waveforms. Further, it is argued that the nonlinear, adaptive mechanisms that
      produce the second-order kernel are involved in shaping the time course of the
      response. Patients with large, but abnormally delayed mERG responses (first-order
      kernel), do not have a detectable second-order kernel. It is speculated that a
      markedly diminished second-order kernel is diagnostic of outer plexiform layer
      damage, not inner plexiform layer damage as is commonly assumed.

PMID- 10925247
TI  - Cutting edge: cutting edge commentary: a Copernican revolution? Doubts about the
      danger theory.
AB  - The immune system is often said to function by "self-nonself" discrimination.
      Recently, some have argued that it actually detects "danger" or "strangers".
      There are problems with all of these points of view. Given that the immune system
      has been cobbled together throughout evolution and uses a diverse array of innate
      and adaptive defense mechanisms, it may not be possible to account for immunity
      within one "paradigm" or another.

PMID- 10925248
TI  - Cutting edge: contribution of NK cells to the homing of thymic CD4+NKT cells to
      the liver.
AB  - In contrast to peripheral lymphoid organs, in the liver a high proportion of T
      cells are CD4+NKT cells. We have previously reported that LFA-1 plays a pivotal
      role in the homing of thymic CD4+NKT cells to the liver. In the present study, we
      further assessed which cell type participates in the homing of thymic CD4+NKT
      cells to the liver. The accumulation of donor thymocyte-derived CD4+NKT cells in
      the liver of SCID mice that had been reconstituted with thymocytes from C57BL/6
      mice was severely impaired by in vivo depletion of NK cells, but not Kupffer
      cells in recipients. These results suggest that NK cells participate in the
      homing of thymic CD4+NKT cells to the liver. We assume that LFA-1 expressed on NK
      cells is involved in this mechanism.

PMID- 10925249
TI  - Cutting edge: naive T cells masquerading as memory cells.
AB  - This study shows that naive CD8 T cells can acquire characteristics of memory T
      cells in the absence of stimulation with specific Ag simply by the process of
      homeostatic proliferation under lymphopenic conditions. This Ag-independent T
      cell differentiation pathway did not result in up-regulation of early activation
      markers (CD69, CD25, CD71), but expression of several memory markers (CD44,
      CD122, Ly6C) increased progressively with successive divisions. These markers
      were then stably expressed, and these cells also became more responsive
      functionally to specific Ag. Thus, all "memory" phenotype T cells in an
      individual may not be true Ag-experienced cells and may include naive cells
      masquerading as memory cells. These findings are specially relevant in cases of
      disease or treatment-induced lymphopenia such as in HIV-infected individuals or
      transplant recipients. In addition, this study may have implications for
      autoimmunity because homeostatic proliferation of naive T cells requires
      interaction with self peptide plus MHC molecules.

PMID- 10925250
TI  - Cutting edge: essential role of phospholipase C-gamma 2 in B cell development and
      function.
AB  - Cross-linking of the B cell Ag receptor (BCR) induces the tyrosine
      phosphorylation of multiple cellular substrates, including phospholipase C (PLC)
      gamma 2, which is involved in the activation of the phosphatidylinositol pathway.
      To assess the importance of PLC-gamma 2 in murine lymphopoiesis, the PLC-gamma 2
      gene was inducibly ablated by using IFN-regulated Cre recombinase. Mice with a
      neonatally induced loss of PLC-gamma 2 function displayed reduced numbers of
      mature conventional B cells and peritoneal B1 cells and defective responses in
      vitro to BCR stimulation and in vivo to immunization with thymus-independent type
      II Ags. In contrast, T cell development and TCR-mediated proliferation were
      normal. Taken together, PLC-gamma 2 is a critical component of BCR signaling
      pathways and is required to promote B cell development.

PMID- 10925251
TI  - The NF-kappa B cascade is important in Bcl-xL expression and for the anti
      apoptotic effects of the CD28 receptor in primary human CD4+ lymphocytes.
AB  - We explored the role of the NF-kappa B pathway in the survival of primary human
      CD4+ T lymphocytes during CD28 costimulation. Transduction of proliferating CD4+
      T cells with a tetracycline-regulated retrovirus encoding for a dominant
      interfering, degradation-resistant I-kappaBalpha (inhibitor of kappa B alpha
      factor) mutant induced apoptosis. Using DNA arrays, we show that Bcl-xL features
      as a prominent anti-apoptotic member among a number of early CD28-inducible
      genes. A 1.2-kb segment of the proximal Bcl-xL promoter, linked to a luciferase
      reporter, responded to CD3/CD28 stimulation in Jurkat cells. Mutation of an NF
      kappa B site around -840 decreased, while ectopic expression of I-kappa B kinase
      beta (IKK beta) enhanced reporter gene activity. Na+-salicylate and
      cyclopentenone PGs, direct inhibitors of IKK beta, interfered in the activation
      of the Bcl-xL promoter and induced apoptosis in CD28-costimulated CD4+ T cells.
      Moreover, salicylate blocked nuclear localization of NF-kappa B factors that bind
      to the NF-kappa B binding site in the Bcl-xL promoter, as well as the expression
      of Bcl-xL protein. HuT-78, a lymphoblastoid T cell line with constitutive NF
      kappa B activity, contained elevated levels of Bcl-xL protein and, similar to
      proliferating CD4+ T cells, was resistant to apoptotic stimuli such as anti-Fas
      and TNF-alpha. In contrast, the same stimuli readily induced apoptosis in a
      Jurkat T cell clone with no detectable Bcl-xL expression. Jurkat BMS2 cells also
      differed from HuT-78 in collapse of mitochondrial membrane potential and
      superoxide generation in the mitochondrium. Taken together, these data
      demonstrate that CD3/CD28-induced activation of IKK beta and expression of Bcl-xL
      promote the survival of primary human CD4+ T lymphocytes.

PMID- 10925252
TI  - Infection of CD4+ memory T cells by HIV-1 requires expression of
      phosphodiesterase 4.
AB  - Using PCR to monitor HIV-1 RNA genome reverse transcription and nuclear import of
      preintegration complexes, we found that memory, but not naive, CD4+ T cells could
      support transport of HIV-1 DNA to nuclei upon TCR/CD3 and IL-2 stimulation.
      Moreover, memory CD4+ T cells, unlike naive CD4+ T cells, express high levels of
      phosphodiesterase 4 (PDE4) constitutively. Selective blocking of PDE4 activity
      inhibited IL-2R expression and thereby led to abolishing HIV-1 DNA nuclear import
      in memory T cells; however, full-length viral DNA synthesis was not affected.
      Thus, blocking PDE4 prevents initiation of HIV-1 DNA circle formation in T cells.
      The fact that PDE4 is expressed constitutively at higher levels in memory vs
      naive CD4+ T cells may help HIV-1 readily infect memory T cells.

PMID- 10925253
TI  - Defective Th function induced by a dominant-negative cAMP response element
      binding protein mutation is reversed by Bcl-2.
AB  - cAMP response element binding protein (CREB) is a critical regulator of diverse
      stimulus-dependent transcriptional events. Following TCR stimulation, CREB is
      rapidly induced in CD4+ Th cell precursors, but not in effector Th cells.
      However, its role in mature T cell function is incompletely defined. Transgenic
      mice expressing a CREB dominant-negative (dn) mutation in the T cell lineage
      exhibited normal T cell development in the thymus, normal T cell homeostasis in
      the periphery, and normal T cell clonal expansion following Ag challenge.
      However, this mutation caused selective inhibition of Th cell function in vitro
      and in vivo, and increased susceptibility of Th cells to activation-induced cell
      death. Th cells expressing the CREB-dn mutation contained reduced levels of the
      inhibitor of programmed cell death, BCL-2; overexpression of BCL-2 in transgenic
      mice reversed both susceptibility to activation-induced cell death in CREB-dn T
      cells and the defect in effector cytokine production. Thus, CREB plays a critical
      role in Th cell function and development of Th cell-mediated adaptive immune
      responses, at least in part, by inhibiting stimulus-dependent cell death.

PMID- 10925254
TI  - Ly-49P activates NK-mediated lysis by recognizing H-2Dd.
AB  - Little is known regarding the ligand specificity of Ly-49 activating receptor
      subfamily members expressed by NK cells. A new Ly-49 activating receptor related
      to Ly-49A in its extracellular domain, designated Ly-49P, was recently cloned
      from 129 strain mice. We independently cloned an apparent allele of Ly-49P
      expressed by nonobese diabetic and nonobese diabetes-resistant mouse strain NK
      cells. We found it to be reactive with the A1 Ab thought to recognize a
      polymorphic epitope expressed only by the Ly-49A inhibitory receptor of the
      C57BL/6 strain. Rat RNK-16 cells transfected with Ly-49P mediated reverse Ab
      dependent cellular cytotoxicity of FcR-positive target cells, indicating that Ly
      49P can activate NK-mediated lysis. We determined that RNK-16 lysis of Con A
      blasts induced by Ly-49P was MHC dependent, resulting in efficient lysis of H-2Dd
      bearing targets. We found that the Dd alpha1/alpha2 domain is required for Ly-49P
      mediated RNK-16 activation, as determined by exon shuffling and transfection.
      Thus, Ly-49P is the second activating Ly-49 receptor demonstrated to induce NK
      cytotoxicity by recognizing a class I MHC molecule.

PMID- 10925255
TI  - Differential role of p38 and c-Jun N-terminal kinase 1 mitogen-activated protein
      kinases in NK cell cytotoxicity.
AB  - The serine-threonine mitogen-activated protein kinase (MAPK) family includes
      extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and
      p38 kinases. In NK cells, spontaneous or Ab-mediated recognition of target cells
      leads to activation of an ERK-2 MAPK-dependent biochemical pathway(s) involved in
      the regulation of NK cell effector functions. Here we assessed the roles of p38
      and JNK MAPK in NK cell-mediated cytotoxicity. Our data indicate that p38 is
      activated in primary human NK cells upon stimulation with immune complexes and
      interaction with NK-sensitive target cells. FcgammaRIIIA-induced granule
      exocytosis and both spontaneous and Ab-dependent cytotoxicity were reduced in a
      dose-dependent manner in cells pretreated with either of two specific inhibitors
      of this kinase. Target cell-induced IFN-gamma and FcgammaRIIIA-induced TNF-alpha
      mRNA accumulation was similarly affected under the same conditions. Lack of
      inhibition of NK cell cytotoxicity in cells overexpressing an inactive form of
      JNK1 indicates that this kinase, activated only upon FcgammaRIIIA ligation, does
      not play a significant role in cytotoxicity. These data underscore the
      involvement of p38, but not JNK1, in the molecular mechanisms regulating NK cell
      cytotoxicity.

PMID- 10925256
TI  - Response of murine gamma delta T cells to the synthetic polypeptide poly
      Glu50Tyr50.
AB  - Random heterocopolymers of glutamic acid and tyrosine (pEY) evoke strong,
      genetically controlled immune responses in certain mouse strains. We found that
      pE50Y50 also stimulated polyclonal proliferation of normal gamma delta, but not
      alpha beta, T cells. Proliferation of gamma delta T cells did not require prior
      immunization with this Ag nor the presence of alpha beta T cells, but was
      enhanced by IL-2. The gamma delta T cell response proceeded in the absence of
      accessory cells, MHC class II, beta 2-microglobulin, or TAP-1, suggesting that Ag
      presentation by MHC class I/II molecules and peptide processing are not required.
      Among normal splenocytes, as with gamma delta T cell hybridomas, the response was
      strongest with V gamma 1+ gamma delta T cells, and in comparison with related
      polypeptides, pE50Y50 provided the strongest stimulus for these cells. TCR gene
      transfer into a TCR-deficient alpha beta T cell showed that besides the TCR, no
      other components unique to gamma delta T cells are needed. Furthermore,
      interactions between only the T cells and pE50Y50 were sufficient to bring about
      the response. Thus, pE50Y50 elicited a response distinct from those of T cells to
      processed/presented peptides or superantigens, consistent with a mechanism of Ig
      like ligand recognition of gamma delta T cells. Direct stimulation by ligands
      resembling pE50Y50 may thus selectively evoke contributions of gamma delta T
      cells to the host response.

PMID- 10925257
TI  - Defective thymocyte development and perturbed homeostasis of T cells in STAT
      induced STAT inhibitor-1/suppressors of cytokine signaling-1 transgenic mice.
AB  - Previous experiments have shown that STAT-induced STAT inhibitor-1 (SSI-1; also
      named suppressors of cytokine signaling-1 (SOCS-1) or Janus kinase binding
      protein) is predominantly expressed in lymphoid organs and functions in vitro as
      a negative regulator of cytokine signaling. To determine the function of SOCS-1
      in vivo, we generated SSI-1 transgenic mice using the lck proximal promoter that
      drives transgene expression in T cell lineage. In thymocytes expressing SSI-1
      transgene, tyrosine phosphorylation of STATs in response to cytokines such as IFN
      gamma, IL-6, and IL-7 was inhibited, suggesting that SSI-1 suppresses cytokine
      signaling in primary lymphocytes. In addition, lck-SSI-1 transgenic mice showed a
      reduction in the number of thymocytes as a result of the developmental blocking
      during triple-negative stage. They also exhibited a relative increase in the
      percentage of CD4+ T cells, a reduction in the number of gammadelta T cells, as
      well as the spontaneous activation and increased apoptosis of peripheral T cells.
      Thus, enforced expression of SSI-1 disturbs the development of thymocytes and the
      homeostasis of peripheral T cells. All these features of lck-SSI-1 transgenic
      mice strikingly resemble the phenotype of mice lacking common gamma-chain or
      Janus kinase-3, suggesting that transgene-derived SSI-1 inhibits the functions of
      common gamma-chain-using cytokines. Taken together, these results suggest that
      SSI-1 can also inhibit a wide variety of cytokines in vivo.

PMID- 10925258
TI  - T cell reactivity with allergoids: influence of the type of APC.
AB  - The use of allergoids for allergen-specific immunotherapy has been established
      for many years. The characteristic features of these chemically modified
      allergens are their strongly reduced IgE binding activity compared with the
      native form and the retained immunogenicity. T cell reactivity of chemically
      modified allergens is documented in animals, but in humans indirect evidence of
      reactivity has been concluded from the induction of allergen-specific IgG during
      immunotherapy. Direct evidence of T cell reactivity was obtained recently using
      isolated human T cells. To obtain further insight into the mechanism of action of
      allergoids, we compared the Ag-presenting capacity of different APC types,
      including DC and macrophages, generated from CD14+ precursor cells from the blood
      of grass pollen allergic subjects, autologous PBMC, and B cells. These APC were
      used in experiments together with Phl p 5-specific T cell clones under
      stimulation with grass pollen allergen extract, rPhl p 5b, and the respective
      allergoids. Using DC and macrophages, allergoids exhibited a pronounced and
      reproducible T cell-stimulating capacity. Responses were superior to those with
      PBMC, and isolated B cells failed to present allergoids. Considerable IL-12
      production was observed only when using the DC for Ag presentation of both
      allergens and allergoids. The amount of IL-10 in supernatants was dependent on
      the phenotype of the respective T cell clone. High IL-10 production was
      associated with suppressed IL-12 production from the DC in most cases. In
      conclusion, the reactivity of Th cells with allergoids is dependent on the type
      of the APC.

PMID- 10925259
TI  - Recirculatory and sessile CD4+ T lymphocytes differ on CD45RC expression.
AB  - CD4+ T cell subsets are unequally distributed in rat secondary lymphoid organs.
      Those with the memory phenotype CD45RClow Thy-1- L-selectin- are present at a
      higher frequency in Peyer's patches (PP) than in lymph nodes and spleen, and
      increase in numbers with age in all three tissues, particularly in the PP. Homing
      experiments revealed that CD4+ T cells that recirculate through secondary
      lymphoid organs are mainly CD45RChigh. It was also apparent that the ability of
      recirculating cells to enter different lymphoid organs varies; less cells enter
      PP than the spleen or lymph nodes. Our results also reveal the existence of a
      nonrecirculating population of CD4+ T cells in secondary lymphoid organs, which
      are predominantly, if not exclusively, CD45RClow. Our results show that secondary
      lymphoid organs differ in their CD4+ T cell subset composition as a consequence
      of having different ratios of recirculatory:nonrecirculatory CD4+ T cells, and
      these cells display a different CD45RC phenotype.

PMID- 10925260
TI  - Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced
      tolerance.
AB  - Hapten sensitization through UV-exposed skin induces hapten-specific tolerance
      that can be adoptively transferred by injecting T lymphocytes into naive
      recipients. The exact phenotype of T cells responsible for inhibiting the immune
      response and their mode of action remain unclear. Evidence exists that CTLA-4
      negatively regulates T cell activation. We addressed whether CTLA-4 is involved
      in the transfer of UV-induced tolerance. Injection of lymph node cells from mice
      that were sensitized with dinitrofluorobenzene (DNFB) through UV-irradiated skin
      inhibited induction of contact hypersensitivity against DNFB in the recipient
      animals. When CTLA-4+ cells were depleted, transfer of suppression was lost.
      Likewise, significantly fewer lymphocytes enriched for CTLA-4+ cells were
      necessary to transfer suppression than unfractionated cells. Expression of CTLA-4
      appears to be functionally relevant, since in vivo injection of a blocking anti
      CTLA-4 Ab was able to break UV-induced tolerance and inhibited transfer of
      suppression. Upon stimulation with dendritic cells in the presence of the water
      soluble DNFB analogue, DNBS, CTLA-4+ T cells from DNFB-tolerized mice secreted
      high levels of IL-10, TGF-beta, and IFN-gamma; low levels of IL-2; and no IL-4,
      resembling the cytokine pattern of T regulatory 1 cells. Ab blocking of CTLA-4
      resulted in inhibition of IL-10 release. Accordingly, transfer of tolerance was
      not observed when recipients were treated with an anti-IL-10 Ab. Hence we propose
      that T cells, possibly of the T regulatory 1 type, transfer UV-mediated
      suppression through the release of IL-10. Activation of CTLA-4 appears to be
      important in this process.

PMID- 10925261
TI  - Early ontogeny of thymocytes in pigs: sequential colonization of the thymus by T
      cell progenitors.
AB  - Successive colonization of the thymus by waves of thymocyte progenitors has been
      described in chicken-quail chimeras and suggested from studies in mice. In swine,
      we show that the first CD3epsilon-bearing thymocytes appear on day 40 of
      gestation (DG40). These early thymocytes were CD3epsilonhigh and belonged to the
      gammadelta T cell lineage. Mature CD3epsilonhigh alphabeta thymocytes were
      observed 15 days later (DG55), and their occurrence was preceded by the
      appearance of CD3epsilonlow thymocytes (DG45). Thereafter, we observed transient
      changes in thymocyte subset composition (DG56-DG74), which can be explained by a
      gap in pro-T cell delivery to the thymus. This delivery gap corresponds with the
      expression of the pan-leukocyte CD45 and pan-myelomonocytic SWC3a markers in
      fetal liver and bone marrow and is probably caused by shifting of primary
      lymphopoiesis between these organs. Therefore, we conclude that the embryonic
      thymus is colonized by at least two successive waves of hemopoietic progenitors
      during embryogenesis and that the influx of thymocyte progenitors is
      discontinuous. Surface immunophenotyping and cell cycle analysis of thymocyte
      subsets allowed us to compare thymocyte differentiation in pigs with that
      described for rodents and humans and to propose a model for T cell lymphopoiesis
      in swine. We also observed that the porcine IL-2Ralpha (CD25), a typical
      differentiation marker of pre-T cells in mice and humans, was not expressed on
      thymocyte precursors in pigs and could only be found on mature thymocytes.
      Finally, we observed a subset of TCRgammadelta+ thymocytes that were cycling late
      during their development in the thymus.

PMID- 10925262
TI  - Differential splicing of antigen-encoding RNA reduces endogenous epitope
      presentation that regulates the expansion and cytotoxicity of T cells.
AB  - The activation of CTLs is dependent on the recognition of MHC-bound peptide
      present on the surface of APCs. We give evidence in this study that differential
      splicing of Ag-encoding RNA can decrease the antigenic dose in APCs and regulate
      the recall of human memory CTLs. Differential splicing of RNA that encoded an
      immunodominant HLA-B8-restricted CTL epitope of EBV reduced the functional
      presentation of this epitope, and consequently the in vitro expansion and
      activity of CTLs, as measured by MHC/peptide-tetramer staining and cytotoxicity
      assays. The reduced activity of the stimulated CTLs was not only due to lower
      numbers of Ag-specific CTLs but, surprisingly, was also characterized by
      decreased cytotoxicity of the CTLs to target cells presenting limiting amounts of
      the peptide epitope. As indicated by TCR repertoire analysis, the reduction in
      CTL activity was not caused by stimulation of distinct populations of TCR
      clonotypes. This study demonstrates how a common eukaryotic posttranscriptional
      mechanism of gene regulation can modulate the endogenous presentation of Ag and
      ultimately contribute to the fine tuning of immunological memory cells, which are
      important in the fight against pathogens and tumors and in autoimmunity.

PMID- 10925263
TI  - Cytokine production and killer activity of NK/T-NK cells derived with IL-2, IL
      15, or the combination of IL-12 and IL-18.
AB  - NK cell populations were derived from murine splenocytes stimulated by IL-2, IL
      15, or the combination of IL-12 and IL-18. Whereas NK cells derived with the
      latter cytokines consisted of an homogeneous population of NK cells (DX5+CD3-),
      those derived with IL-2 or IL-15 belonged to two different populations, namely NK
      cells (DX5+CD3-) and T-NK cells (DX5+CD3+). Among NK cells, only those derived
      with IL-12/IL-18 produced detectable levels of cytokines, namely IFN-gamma, IL
      10, and IL-13 (with the exception of IL-13 production by NK cells derived with IL
      2). As for T-NK cells, IL-2-stimulated cells produced a wide range of cytokines,
      including IL-4, IL-5, IL-9, IL-10, and IL-13, but no IFN-gamma, whereas IL-15
      derived T-NK cells failed to produce any cytokine. Switch-culture experiments
      indicated that T-NK cells derived in IL-2 and further stimulated with IL-12/IL-18
      produced IFN-gamma and higher IL-13 levels. Next, we observed that NK/T-NK cell
      populations exerted distinct effects on Ig production by autologous splenocytes
      according to the cytokines with which they were derived. Thus, addition of NK
      cells derived in IL-12/IL-18 inhibited Ig production and induced strong
      cytotoxicity against splenocytes, whereas addition of NK or T-NK cells grown in
      IL-2 or IL-15 did not. Experiments performed in IFN-gammaR knockout mice
      demonstrated that IFN-gamma was not involved in the killer activity of IL-12/IL
      18-derived NK cells. The hypothesis that their cytotoxic activity was related to
      the induction of target apoptosis was confirmed on murine A20 lymphoma cells.
      Experiments performed in MRL/lpr mice indicated that IL-12/IL-18-derived NK cells
      displayed their distinct killer activity through a Fas-independent pathway.
      Finally, perforin was much more expressed in IL-12/IL-18-derived NK cells as
      compared with IL-2- or IL-15-derived NK cells, an observation that might explain
      their unique cytotoxicity.

PMID- 10925264
TI  - Distinct molecular mechanisms of Fas resistance in murine B lymphoma cells.
AB  - A panel of murine B lymphoma cell lines, which express different levels of Fas,
      was extensively studied for sensitivity to Fas-mediated death signals via an anti
      Fas mAb and Fas ligand-bearing cell lines. Expression of the Fas receptor on the
      B lymphoma cell lines did not correlate with their capacity to undergo Fas
      mediated apoptosis. Moreover, Fas-associated death domain protein recruitment to
      the death-inducing signaling complex (DISC) complex occurred in all cell lines
      expressing Fas, regardless of whether they were sensitive to Fas-mediated death.
      Interestingly, the protein synthesis inhibitor, cycloheximide, and protein kinase
      C inhibitors, such as bisindolylmaleimide, rendered one of the resistant cell
      lines, CH33, sensitive to signals from the Fas receptor, although the levels of
      Fas were unchanged. This suggests that constitutive PKC activation plays a role
      in Fas resistance, perhaps by up-regulating NF-kappaB or Bcl-2 family members.
      Interestingly, CH33 demonstrated caspase 8 activity upon engagement of the Fas
      receptor in the absence of pharmacological manipulation, suggesting that the
      block in apoptosis is downstream of the DISC complex. In contrast, the fact that
      Fas-associated death domain protein was recruited to the DISC complex in other
      resistant lines, such as WEHI-231, with no caspase 8 activation indicates that
      these cells may be blocked within the DISC complex. Indeed, Western blot analysis
      showed that WEHI-231 expressed an isoform of FLICE-like inhibitory protein
      (cFLIPL), an antiapoptotic protein within the DISC. These studies provide
      evidence that murine B lymphoma cells utilize different molecular mechanisms
      along the Fas-signaling cascade to block apoptosis.

PMID- 10925265
TI  - Oligosaccharides of hyaluronan are potent activators of dendritic cells.
AB  - The extracellular matrix component hyaluronan (HA) exists physiologically as a
      high m.w. polymer but is cleaved at sites of inflammation, where it will be
      contacted by dendritic cells (DC). To determine the effects of HA on DC, HA
      fragments of different size were established. Only small HA fragments of tetra-
      and hexasaccharide size (sHA), but not of intermediate size (m.w. 80, 000
      200,000) or high m.w. HA (m.w. 1,000,000-600,000) induced immunophenotypic
      maturation of human monocyte-derived DC (up-regulation of HLA-DR, B7-1/2, CD83,
      down-regulation of CD115). Likewise, only sHA increased DC production of the
      cytokines IL-1beta, TNF-alpha, and IL-12 as well as their allostimulatory
      capacity. These effects were highly specific for sHA, because they were not
      induced by other glycosaminoglycans such as chondroitin sulfate or heparan
      sulfate or their fragmentation products. Interestingly, sHA-induced DC maturation
      does not involve the HA receptors CD44 or the receptor for hyaluronan-mediated
      motility, because DC from CD44-deficient mice and wild-type mice both responded
      similarly to sHA stimulation, whereas the receptor for hyaluronan-mediated
      motility is not detectable in DC. However, TNF-alpha is an essential mediator of
      sHA-induced DC maturation as shown by blocking studies with a soluble TNFR1.
      These findings suggest that during inflammation, interaction of DC with small HA
      fragments induce DC maturation.

PMID- 10925266
TI  - Transgenic expression of Ly49A on T cells impairs a specific antitumor response.
AB  - Inhibitory MHC receptors determine the reactivity and specificity of NK cells.
      These receptors can also regulate T cells by modulating TCR-induced effector
      functions such as cytotoxicity, cytokine production, and proliferation. Here we
      have assessed the capacity of mouse T cells expressing the inhibitory MHC class I
      receptor Ly49A to respond to a well-defined tumor Ag in vivo using Ly49A
      transgenic mice. We find that the presence of Ly49A on the vast majority of
      lymphocytes prevents the development of a significant Ag-specific CD8+ T cell
      response and, consequently, the rejection of the tumor. Despite minor alterations
      in the TCR repertoire of CD8+ T cells in the transgenic lines, precursors of
      functional tumor-specific CD8+ T cells exist but could not be activated most
      likely due to a lack of appropriate CD4+ T cell help. Surprisingly, all of these
      effects are observed in the absence of a known ligand for the Ly49A receptor as
      defined by its ability to regulate NK cell function. Indeed, we found that the
      above effects on T cells may be based on a weak interaction of Ly49A with Kb or
      Db class I molecules. Thus, our data demonstrate that enforced expression of a
      Ly49A receptor on conventional T cells prevents a specific immune response in
      vivo and suggest that the functions of T and NK cells are differentially
      sensitive to the presence of inhibitory MHC class I receptors.

PMID- 10925267
TI  - IL-4 is a mediator of IL-12p70 induction by human Th2 cells: reversal of
      polarized Th2 phenotype by dendritic cells.
AB  - IL-12 is a key inducer of Th1-associated inflammatory responses, protective
      against intracellular infections and cancer, but also involved in autoimmune
      tissue destruction. We report that human Th2 cells interacting with monocyte
      derived dendritic cells (DC) effectively induce bioactive IL-12p70 and revert to
      Th0/Th1 phenotype. In contrast, the interaction with B cells preserves polarized
      Th2 phenotype. The induction of IL-12p70 in Th2 cell-DC cocultures is prevented
      by IL-4-neutralizing mAb, indicating that IL-4 acts as a Th2 cell-specific
      cofactor of IL-12p70 induction. Like IFN-gamma, IL-4 strongly enhances the
      production of bioactive IL-12p70 heterodimer in CD40 ligand-stimulated DC and
      macrophages and synergizes with IFN-gamma at low concentrations of both
      cytokines. However, in contrast to IFN-gamma, IL-4 inhibits the CD40 ligand
      induced production of inactive IL-12p40 and the production of either form of IL
      12 induced by LPS, which may explain the view of IL-4 as an IL-12 inhibitor. The
      presently described ability of IL-4 to act as a cofactor of Th cell-mediated IL
      12p70 induction may allow Th2 cells to support cell-mediated immunity in chronic
      inflammatory states, including cancer, autoimmunity, and atopic dermatitis.

PMID- 10925268
TI  - In vitro and in vivo transfection of p21 gene enhances cyclosporin A-mediated
      inhibition of lymphocyte proliferation.
AB  - Cyclosporine has potent antiproliferative properties, some of which may be via
      the induction of the cyclin inhibitor p21. In this study, we describe the effects
      of in vitro and in vivo transfection of p21 in lymphoid and nonlymphoid cells.
      For in vitro studies, p21 sense plasmid DNA was transfected in A-549 cells (lung
      adenocarcinoma cell line) and Jurkat cells (human lymphoid cell line). This in
      vitro transfection of p21 resulted in the inhibition of spontaneous and mitogen
      induced cellular proliferation ([3H]thymidine uptake) and also augmented the
      antiproliferative effects of cyclosporine. In vivo transfection of p21 was
      accomplished in mice via the i.m. injection of p21 sense plasmid DNA complexed
      with cationic lipids. As was the case in the cell lines, p21 mRNA was augmented
      in heart, lung, liver, and spleen 7 days after i.m. injection of p21 sense
      plasmid DNA. The mitogen (anti-CD3)-induced proliferation of splenocytes from p21
      overexpressing mice was significantly decreased, and again this effect was
      augmented by cotreatment with cyclosporine. These novel findings demonstrate the
      potential of targeting the cell cycle directly to inhibit alloimmune activation
      in organ transplantation. This may serve as an alternate strategy to induce
      immunosuppression, perhaps with less toxicity than that which is seen with
      conventional immunosuppressive agents.

PMID- 10925269
TI  - Opening a window on thymic positive selection: developmental changes in the
      influence of cosignaling by integrins and CD28 on selection events induced by TCR
      engagement.
AB  - How TCR and non-TCR signals are integrated by thymocytes to generate a decision
      to undergo either positive or negative selection remains incompletely understood.
      Recent evidence suggests that TCR signal transduction changes its quality during
      thymocyte maturation, but whether the contributions of various cosignaling or
      costimulatory pathways to thymocyte selection also are modified during
      development is unclear. Questions also remain about the possible selective roles
      of specific costimulatory pathways in induction of differentiation vs death among
      thymocytes at any given stage of maturity. To address these issues, a
      quantitative in vitro analysis of initiation of CD4+CD8+ thymocyte
      differentiation as measured by CD69 up-regulation/coreceptor down-modulation was
      conducted in parallel with an analysis of induction of death. Using transfected
      cells varying in their surface display of ICAM-1 or B7.1 along with antibody
      blocking experiments, we demonstrate here that ICAM-1 provides a selective boost
      to signaling for differentiation without substantially affecting induction of
      death among CD4+CD8+ cells, a property that is lost as thymocytes mature further.
      In contrast, B7 engagement enhances both cell activation and death in parallel.
      Based on these data, we propose that the high level of ICAM-1 on cortical
      epithelial cells plays a special role in opening a window between TCR signaling
      for differentiation vs death, permitting efficient initiation of positive
      selection on epithelial ligands. In contrast, late CD28-dependent cosignaling on
      hemopoietic cells in the medulla would help enforce negative selection by
      augmenting the effects of TCR engagement by low levels of high affinity ligands.

PMID- 10925270
TI  - Alpha beta TCR+ cells are a minimal fraction of peripheral CD8+ pool in MHC class
      I-deficient mice.
AB  - MHC class I molecules play a role in the maintenance of the naive peripheral CD8+
      T cell pool. The mechanisms of the peripheral maintenance and the life span of
      residual CD8+ cells present in the periphery of beta 2-microglobulin-deficient
      (beta 2m-/-) mice are unknown. We here show that very few CD8+ cells in beta 2m-/
      mice coexpress CD8 beta, a marker of the thymus-derived CD8+ T cells. Most of
      the CD8 alpha+ cells express CD11c and can be found in beta 2m/RAG-2 double
      deficient mice, demonstrating that these cells do not require rearranged Ag
      receptors for differentiation and survival and may be of dendritic cell lineage.
      Rare CD8 alpha+CD8 beta+ cells can be detected following in vivo alloantigenic
      stimulation 2 wk after the adult thymectomy. Selective MHC class I expression by
      bone marrow-derived cells does not lead to an accumulation of CD8 beta+ cells in
      beta 2m-/- mice. These findings demonstrate that 1) thymic export of CD8+ T cells
      in beta 2m-/- mice is reduced more severely than previously thought; 2) non-T
      cells expressing CD8 alpha become prominent when CD8+ T cells are virtually
      absent; 3) at least some beta 2m-/- CD8+ T cells have a life span in the
      periphery comparable to wild-type CD8+ cells; and 4) similar ligands induce
      positive selection in the thymus and survival of CD8+ T cells in the periphery.

PMID- 10925271
TI  - CD81 and CD28 costimulate T cells through distinct pathways.
AB  - We have examined the role of CD81 in the activation of murine splenic alphabeta T
      cells. Expression of the CD81 molecule on T cells increases following activation,
      raising the possibility of a role for this molecule in progression of the
      activation process. Using an in vitro costimulation assay, we show that CD81 can
      function as a costimulatory molecule on both CD4+ and CD8+ T cells. This
      costimulation functions independently of CD28, and unlike costimulation through
      CD28, is susceptible to inhibition by cyclosporin A. Strikingly, the pattern of
      cytokine production elicited by costimulation via CD81 is unique. IL-2 production
      was not up-regulated, whereas both IFN-gamma and TNF-alpha expression
      significantly increased. Together our results demonstrate an alternate pathway
      for costimulation of T cell activation mediated by CD81.

PMID- 10925273
TI  - Helicobacter pylori urease binds to class II MHC on gastric epithelial cells and
      induces their apoptosis.
AB  - Infection by Helicobacter pylori leads to injury of the gastric epithelium and a
      cellular infiltrate that includes CD4+ T cells. H. pylori binds to class II MHC
      molecules on gastric epithelial cells and induces their apoptosis. Because urease
      is an abundant protein expressed by H. pylori, we examined whether it had the
      ability to bind class II MHC and induce apoptosis in class II MHC-bearing cells.
      Flow cytometry revealed the binding of PE-conjugated urease to class II MHC+
      gastric epithelial cell lines. The binding of urease to human gastric epithelial
      cells was reduced by anti-class II MHC Abs and by staphylococcal enterotoxin B.
      The binding of urease to class II MHC was confirmed when urease bound to HLA-DR1
      transfected COS-1 (1D12) cells but not to untransfected COS-1 cells. Urease also
      bound to a panel of B cell lines expressing various class II MHC alleles.
      Recombinant urease induced apoptosis in gastric epithelial cells that express
      class II MHC molecules, but not in class II MHC- cells. Also, Fab from anti-class
      II MHC and not from isotype control Abs blocked the induction of apoptosis by
      urease in a concentration-dependent manner. The adhesin properties of urease
      might point to a novel and important role of H. pylori urease in the pathogenesis
      of H. pylori infection.

PMID- 10925272
TI  - Cytolytic mechanisms and expression of activation-regulating receptors on
      effector-type CD8+CD45RA+CD27- human T cells.
AB  - Circulating CD8+ T cells with a CD45RA+CD27- phenotype resemble cytolytic
      effector cells because they express various cytolytic mediators and are able to
      execute cytotoxicity without prior stimulation in vitro. We here demonstrate that
      CD8+CD45RA+CD27- T cells can use both granule exocytosis and Fas/Fas ligand
      pathways to induce apoptosis in target cells. The availability of these cytolytic
      mechanisms in circulating T cells suggests that the activity of these cells must
      be carefully controlled to prevent unwanted tissue damage. For this reason, we
      analyzed the expression of surface receptors that either enhance or inhibit T
      cell function. Compared with memory-type cells, effector cells were found to
      express normal levels of CD3epsilon and TCRzeta and relatively high levels of
      CD8. CTLA-4 was absent from freshly isolated effector cells, whereas a limited
      number of unstimulated memory cells expressed this molecule. In line with recent
      findings on CD8+CD28- T cells, CD45RA+CD27- T cells were unique in the abundant
      expression of NK cell-inhibitory receptors, both of Ig superfamily and C-type
      lectin classes. Binding of NK cell-inhibitory receptors to classical and
      nonclassical MHC class I molecules may inhibit the activation of the cytolytic
      machinery induced by either Ag receptor-specific or nonspecific signals in
      CD8+CD45RA+CD27- T cells.

PMID- 10925274
TI  - Regulation of gene expression of murine MD-1 regulates subsequent T cell
      activation and cytokine production.
AB  - The immunoadhesin (OX2:Fc) comprising the extracellular domain of murine OX2
      linked to IgG2aFc, inhibits production of IL-2 and IFN-gamma by activated T cells
      and increases allograft and xenograft survival in vivo. Increased expression of
      OX2 on dendritic cells (DC) in vivo following preimmunization via the portal vein
      is also associated with elevated expression of MD-1. We have used antisense
      oligodeoxynucleotides (ODNs) to MD-1 to investigate the effect of inhibition of
      expression of MD-1 by DC on their function as allostimulatory cells. We also
      investigated by FACS analysis the cell surface expression of OX2, CD80, and CD86
      on DC incubated with ODN-1 blocking MD-1 expression. Blocking MD-1 gene
      expression inhibits surface expression of CD80 and CD86, but not of OX2. DC
      incubated with ODN-1 to MD-1 did not stimulate IL-2 or IFN-gamma production, but
      generated cells able to suppress, in a second culture of fresh DC plus allogeneic
      T cells, production of IL-2 and IFN-gamma. This inhibition was blocked by anti
      OX2 mAb. Infusion of DC preincubated with ODN-1 prolonged renal allograft
      survival, an effect also reversed by anti-OX2 mAb. By FACS, incubation of DC with
      anti-MD-1 Ab to promote capping eliminated cell surface expression of MD-1 and
      CD14 without altering DEC205, DC26, CD80, CD86, or OX2 expression. Thus OX2 and
      MD-1 are independent surface molecules on DC that may reciprocally regulate T
      cell stimulation. MD-1 is linked to CD14, a "danger receptor complex," and
      activation of this complex can regulate cell surface expression of CD80/CD86,
      which signal T cells.

PMID- 10925275
TI  - IFN-alpha and IL-12 induce IL-18 receptor gene expression in human NK and T
      cells.
AB  - IL-18 is a proinflammatory cytokine that enhances innate and specific Th1 immune
      responses. During microbial infections, IL-18 is produced by activated
      macrophages. IL-18 exerts its effects in synergy with IFN-alpha or IL-12 to
      induce IFN-gamma. Here we show that in human NK and T cells IFN-alpha and IL-12
      strongly up-regulate mRNA expression of the IL-18R components, accessory protein
      like (AcPL) and IL-1R-related protein (IL-1Rrp). In addition, IFN-alpha enhanced
      the expression of MyD88, an adaptor molecule involved in IL-18 signaling.
      Pretreatment of T cells with IFN-alpha or IL-12 enhanced IL-18-induced NF-kappaB
      activation and sensitized the cells to respond to lower concentrations of IL-18.
      AcPL and IL-1Rrp genes were strongly expressed in T cells polarized with IL-12,
      whereas in IL-4-polarized cells these genes were expressed at very low levels,
      indicating that AcPL and IL-1Rrp genes are preferentially expressed in Th1 cells.
      In conclusion, the results suggest that IFN-alpha and IL-12 enhance innate as
      well as Th1 immune response by inducing IL-18R expression.

PMID- 10925276
TI  - Loss of IL-6 receptor expression in cervical carcinoma cells inhibits autocrine
      IL-6 stimulation: abrogation of constitutive monocyte chemoattractant protein-1
      production.
AB  - IL-6 is synthesized in human papilloma virus (HPV)-transformed cervical carcinoma
      cell lines and is supposed to stimulate these cells in an autocrine manner. We
      studied IL-6 production and responsiveness in nonmalignant HPV-transformed
      keratinocytes and cervical carcinoma cells in detail. IL-6 was detected in
      cervical carcinomas in situ. Correspondingly, HPV-positive carcinoma cell lines
      expressed high IL-6 levels. However, these carcinoma cell lines showed low
      responsiveness to IL-6 as revealed by low constitutive STAT3 binding activity,
      which was not further enhanced by exogenous IL-6. In contrast, in vitro
      transformed nonmalignant keratinocytes without endogenous IL-6 production
      strongly responded to exogenous IL-6 with activation of STAT3. STAT3 protein
      expression levels were comparable in both responsive and nonresponsive cell
      lines. Also, gp130, the upstream signal-transducing receptor subunit conveying IL
      6 signals into the cell, was expressed in all tested cell lines. However, the IL
      6 binding subunit gp80 was lost in the malignant cells. Addition of soluble gp80
      was sufficient to restore IL-6 responsiveness in carcinoma cells as shown by
      enhanced activation of STAT3 binding activity. As a consequence of the restored
      IL-6 responsiveness, carcinoma cells strongly produced the chemokine monocyte
      chemoattractant protein-1 (MCP-1). Our data demonstrate that cervical carcinoma
      cells producing high amounts of IL-6 only weakly respond to IL-6 in an autocrine
      manner due to limited gp80 expression. While production of IL-6 might contribute
      to a local immunosuppressive effect, silencing an autocrine IL-6 response
      prevents constitutive production of the mononuclear cell-attracting chemokine MCP
      1. Both mechanisms might help the tumor to escape the immune system.

PMID- 10925277
TI  - Nondepleting anti-CD4 has an immediate action on diabetogenic effector cells,
      halting their destruction of pancreatic beta cells.
AB  - The induction of tolerance in a primed immune system is a major aim for therapy
      in autoimmunity and transplant rejection. In this paper, we investigate the
      action of the nondepleting anti-CD4 Ab, YTS 177. Although this Ab is
      nondepleting, we have demonstrated a direct action in vivo on activated effector
      cells. We show that the Ab inhibits transfer of insulin-dependent diabetes
      mellitus by the CD4+ Th1 clone BDC2.5 to nonobese diabetic mice. Furthermore, we
      show that this Ab acts directly on diabetogenic effector cells because it
      prevented BDC2.5-induced insulin-dependent diabetes mellitus in nonobese diabetic
      scid recipients in the absence of other T cells. The Ab halts the diabetic
      process even when it is administered after the BDC2.5 cells have infiltrated the
      pancreas and destruction of islets is already underway. This is accompanied by an
      immediate decrease in proinflammatory cytokine production with cessation of beta
      cell destruction and disappearance of infiltrating cells from the pancreas,
      leaving any remaining beta cells intact. These data suggest that Abs such as this
      may be effective not only because they induce regulatory T cells but also because
      they are able to directly prevent effector cell function.

PMID- 10925278
TI  - Transduction of dendritic cells with Bcl-xL increases their resistance to
      prostate cancer-induced apoptosis and antitumor effect in mice.
AB  - We have shown that prostate cancer (PCa) causes apoptosis of dendritic cells
      (DC), which might block the development of specific antitumor immune responses.
      Analysis of murine prostatic carcinoma tissues revealed the significant decrease
      in intratumoral DC number during tumor progression. We demonstrated that the
      cytokine-mediated increase in DC survival was accompanied by an elevated
      expression of the anti-apoptotic protein Bcl-xL. Next, we evaluated the
      resistance to tumor-induced apoptosis and the antitumor efficiency of genetically
      engineered DC overexpressing Bcl-xL. DC were transduced with an adenoviral vector
      encoding the murine Bcl-xL gene and injected intratumorally. Data analysis
      revealed that treatment of PCa-bearing mice with Bcl-xL-transduced DC resulted in
      significant inhibition of tumor growth compared with the administration of
      nontransduced DC. Thus, our data suggest that the protection of DC from PCa
      induced apoptosis might significantly increase the efficacy of DC-based therapies
      in cancer even in the absence of available tumor-specific Ags.

PMID- 10925279
TI  - CD11c+ eosinophils in the murine thymus: developmental regulation and recruitment
      upon MHC class I-restricted thymocyte deletion.
AB  - Eosinophils are bone marrow-derived cells released into the circulation during
      hypersensitivity reactions and parasitic infections. Under normal conditions most
      eosinophils are tissue bound, where their physiologic role is unclear. During in
      situ analysis of the thymic microenvironment for CD11c+ dendritic cell
      subpopulations (APC critical in the process of thymic negative selection) a
      discrete population of CD11b/CD11c double-positive cells concentrated in the
      cortico-medullary region of young mice was detected. Thymic CD11c+ cells were
      isolated, and the CD11b+ subpopulation (CD44high, class IIlow, CD11cint) was
      identified as mature eosinophils based on: scatter characteristics, major basic
      protein mRNA expression, and eosinophilic granules. They are hypodense, release
      high levels of superoxide anion, and express CD25, CD69, and mRNA for IL-4 and IL
      13, but not GM-CSF or IL-5, suggesting a distinct state of activation. Thymic
      eosinophils are preferentially recruited during the neonatal period; absolute
      numbers increased 10-fold between 7-14 days to reach parity with dendritic cells
      before diminishing. In a model of acute negative selection, eosinophil numbers
      were increased 2-fold 6 h after cognate peptide injection into MHC class I
      restricted female H-Y TCR transgenic mice. In both peptide-treated female and
      negatively selecting male H-Y TCR mice, clusters of apoptotic bodies were
      associated with eosinophils throughout the thymus. Our data demonstrate a
      temporal and spatial association between eosinophil recruitment and class I
      restricted selection in the thymus, suggesting an immunomodulatory role for
      eosinophils under nonpathological conditions.

PMID- 10925280
TI  - Normal thymic architecture and negative selection are associated with Aire
      expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis
      ectodermal dystrophy (APECED).
AB  - T cell development is tightly controlled by thymic stromal cells. Alterations in
      stromal architecture affect T cell maturation and the development of self
      tolerance. The monogenic autoimmune syndrome APECED (autoimmune
      polyendocrinopathy-candidiasis-ectodermal dystrophy) is characterized by the loss
      of self-tolerance to multiple organs. Although mutations in the autoimmune
      regulator (AIRE) gene are responsible for this disease, the function of AIRE is
      not known. Here we report on the spatial and temporal pattern of murine Aire
      expression during thymic ontogeny and T cell selection. Early during development,
      thymic Aire transcription is critically dependent on RelB and occurs in
      epithelial cells in response to lymphocyte-mediated signals. In adult tissue,
      Aire expression is confined to the medulla and the corticomedullary junction,
      where it is modulated by thymocytes undergoing negative selection. Aire may
      determine thymic stromal organization and with it the induction of self
      tolerance.

PMID- 10925281
TI  - Macrophages present pinocytosed exogenous antigen via MHC class I whereas antigen
      ingested by receptor-mediated endocytosis is presented via MHC class II.
AB  - Macrophages present exogenous Ag either via MHC class I or MHC class II
      molecules. We investigated whether the mode of hemagglutinin (HA) uptake
      influences the class of MHC molecule by which this Ag is presented. Normally, HA
      is ingested by receptor-mediated endocytosis, but this may be switched to
      macropinocytosis and pinocytosis by adding phorbol esters to the cells. This
      switch resulted in altered intracellular routing of ingested Ag and a transition
      from Ag presentation via MHC class II molecules to presentation via MHC class I
      molecules. Similarly, inhibition of receptor-mediated HA endocytosis, by treating
      the cells with the HA receptor destroying enzyme neuraminidase, abrogated Ag
      presentation via MHC class II molecules and induced presentation via MHC class I
      molecules. If, however, under these conditions, receptor-mediated uptake of HA
      was restored, by virtue of HA/anti-HA Ab interaction and subsequent uptake of HA
      via the Fc receptor, presentation via MHC class II was restored as well, whereas
      presentation of HA via MHC class I molecules was no longer detectable. We
      conclude that in macrophages the mode of Ag uptake is decisive in determining via
      which class of MHC molecules Ag is presented: pinocytosis and macropinocytosis
      produce exclusive presentation of exogenous Ag via MHC class I molecules whereas
      receptor-mediated endocytosis leads exclusively to presentation via class II
      molecules.

PMID- 10925282
TI  - Antitumor effects of the mouse chemokine 6Ckine/SLC through angiostatic and
      immunological mechanisms.
AB  - Mouse 6Ckine/SLC (secondary lymphoid tissue chemokine) is a chemotactic factor
      for dendritic cells, T cells, and NK cells in vitro. In addition, mouse
      6Ckine/SLC interacts with the chemokine receptor CXCR3, as do several chemokines
      with antiangiogenic properties. These dual properties of mouse 6Ckine/SLC were
      tested for the induction of an antitumor response by transducing the C26 colon
      carcinoma tumor cell line with a cDNA encoding mouse 6Ckine/SLC. The C26-6CK
      transduced cells showed reduced tumorigenicity in immunocompetent or in nude
      mice. Part of this effect was likely due to angiostatic mechanisms as shown by
      immunohistochemistry and Matrigel assay. C26-6CK tumors were also heavily
      infiltrated with leukocytes, including granulocytes, dendritic cells, and CD8+ T
      cells. In vivo, anti-CD8 treatment increased the tumorigenicity of the C26-6CK
      tumor cells, and tumor-infiltrating CD8+ T cells had the phenotype of memory
      effector cells, suggesting the induction of cytotoxic tumor-specific T
      lymphocytes. On the other hand, anti-asialo-GM1 depletion also increased the
      tumorigenicity of C26-6CK cells, supporting the participation of NK cells.
      Finally, tumor-infiltrating dendritic cells had the phenotype and functional
      features of immature dendritic cells. Overall, these results suggest that mouse
      6Ckine/SLC has strong antitumor effects by inducing both angiostatic, CD8+ T cell
      mediated, and possibly NK-mediated tumor resistance mechanisms.

PMID- 10925283
TI  - Frequent contribution of T cell clonotypes with public TCR features to the
      chronic response against a dominant EBV-derived epitope: application to direct
      detection of their molecular imprint on the human peripheral T cell repertoire.
AB  - In an attempt to provide a global picture of the TCR repertoire diversity of a
      chronic T cell response against a common Ag, we performed an extensive TCR
      analysis of cells reactive against a dominant HLA-A2-restricted EBV epitope
      (hereafter referred to as GLC/A2), obtained after sorting PBL or synovial fluid
      lymphocytes from EBV-seropositive individuals using MHC/peptide multimers.
      Although TCR beta-chain diversity of GLC/A2+ T cells was extensive and varied
      greatly from one donor to another, we identified in most cell lines several
      recurrent Vbeta subsets (Vbeta2, Vbeta4, and Vbeta16 positive) with highly
      conserved TCRbeta complementarity-determining region 3 (CDR3) length and
      junctional motifs, which represented from 11 to 98% (mean, 50%) of GLC/A2
      reactive cells. While TCR beta-chains expressed by these subsets showed limited
      CDR1, CDR2, and CDR3 homology among themselves, their TCR alpha-chains comprised
      the same TCRAV region, thus suggesting hierarchical contribution of TCR alpha
      chain vs TCR beta-chain CDR to recognition of this particular MHC/peptide
      complex. The common occurrence of T cell clonotypes with public TCR features
      within GLC/A2-specific T cells allowed their direct detection within unsorted PBL
      using ad hoc clonotypic primers. These results, which suggest an unexpectedly
      high contribution of public clonotypes to the TCR repertoire against a dominant
      epitope, have several implications for the follow-up and modulation of T cell
      mediated immunity.

PMID- 10925284
TI  - Intestinal microflora and diversification of the rabbit antibody repertoire.
AB  - The rabbit establishes its primary Ab repertoire by somatically diversifying an
      initial repertoire that is limited by restricted VH gene segment usage during VDJ
      gene rearrangement. Somatic diversification occurs in gut-associated lymphoid
      tissue (GALT), and by about 1-2 mo of age nearly all Ig VDJ genes are somatically
      diversified. In other species that are known to establish their primary Ab
      repertoire by somatic diversification, such as chicken, sheep, and cattle,
      diversification appears to be developmentally regulated: it begins before birth
      and occurs independent of exogenous factors. Because somatic diversification in
      rabbit occurs well after birth in GALT, the diversification process may not be
      developmentally regulated, but may require interaction with exogenous factors
      derived from the gut. To test this hypothesis, we examined Ab repertoire
      diversification in rabbits in which the appendix was ligated shortly after birth
      to prevent microbial colonization and all other organized GALT was surgically
      removed. We found that by 12 wk of age nearly 90% of the Ig VDJ genes in PBL were
      undiversified, indicating that intestinal microflora are required for somatically
      diversifying the Ab repertoire. We also examined repertoire diversification in
      sterilely derived remote colony rabbits that were hand raised away from contact
      with conventional rabbits and thereby acquired a different gut microflora. In
      these remote colony rabbits, GALT was underdeveloped, and 70% of the Ig VDJ genes
      in PBL were undiversified. We conclude that specific, currently unidentified
      intestinal microflora are required for Ab repertoire diversification.

PMID- 10925285
TI  - Antigen triggering selectively increases TCRBV gene transcription.
AB  - When the TCR binds Ag it is phosphorylated, internalized, and degraded. We wished
      to examine whether this process was accompanied by a specific concomitant
      increase in TCR mRNA levels. To do this, PBMC and a T cell clone were cultured
      with a series of superantigens and an alloantigen. Only T cells specifically
      responding to an antigenic stimulus had increased levels of TCR beta-chain
      variable (TCRBV)-specific mRNA. This response was apparent after 48 h, peaked
      around 72 h, and was still elevated after 7 days. Increased gene transcription
      appeared to be driven solely by Ag as specific Ag depletion prevented culture
      supernatants transferring this effect. The level of TCRBV mRNA elevation was not
      influenced by the stimulating Ag, but appeared dependent on the gene encoding the
      stimulated TCR. Reporter gene assays, using cloned TCRBV gene promoters,
      confirmed both that TCR gene transcription rises after stimulation and that basal
      and stimulated levels of TCR transcription vary between different TCRBV genes.
      These data conclusively demonstrate that there is no direct relationship between
      TCRBV mRNA and T cell number, and that future repertoire studies must take both
      factors into account.

PMID- 10925286
TI  - Differentiation of monocytes to macrophages switches the Mycobacterium
      tuberculosis effect on HIV-1 replication from stimulation to inhibition:
      modulation of interferon response and CCAAT/enhancer binding protein beta
      expression.
AB  - HIV-1 replication is inhibited in uninflamed lung macrophages and is stimulated
      during tuberculosis. Attempts to recapitulate activation of HIV-1 replication in
      primary monocytes and macrophages ex vivo and in the untreated and PMA-treated
      THP-1 cell line model in vitro have produced opposite results depending on the
      state of differentiation of the cells. After infection with Mycobacterium
      tuberculosis, monocytes enhanced HIV-1 replication and produced a stimulatory 37
      kDa CCAAT/enhancer binding protein beta (C/EBPbeta) transcription factor, whereas
      macrophages suppressed HIV-1 replication and produced an inhibitory 16-kDa
      C/EBPbeta transcription factor. IFN-beta induced inhibitory 16-kDa C/EBPbeta in
      macrophages, but had no effect on C/EBPbeta expression in monocytes. Macrophages,
      but not monocytes, were able to activate IFN-stimulated gene factor-3 (ISGF-3), a
      transcription factor composed of STAT-1, STAT-2, and IFN regulatory factor (IRF)
      9, after infection with M. tuberculosis or stimulation with type I IFN.
      Macrophages expressed IRF-9 DNA-binding activity, but monocytes did not, and
      addition of the IRF-9 component reconstituted ISGF-3 in extracts of IFN-treated
      monocytes. Modulation of IFN responsiveness upon differentiation occurred at
      least in part through a post-transcriptionally regulated increase in IRF-9
      expression. Both monocytes and macrophages maintained IFN responsiveness,
      activating STAT-1 homodimer formation and transcription of the STAT-1 gene after
      IFN stimulation. In addition, both monocytes and macrophages were able to
      activate NF-kappaB upon infection with M. tuberculosis. These results show that
      induction of ISGF-3, expression of the inhibitory 16-kDa C/EBPbeta, and
      suppression of HIV-1 replication via a transcriptional mechanism are macrophage
      specific responses to infection with M. tuberculosis.

PMID- 10925287
TI  - Identification of T cell ligands in a library of peptides covalently attached to
      HLA-DR4.
AB  - While T cells have been clearly implicated in a number of disease processes
      including autoimmunity, graft rejection, and atypical immune responses, the
      precise Ags recognized by the pathogenic T cells have often been difficult to
      identify. This has particularly been true for MHC class II-restricted CD4+ T
      cells. Although such cells can be demonstrated to have undergone clonal expansion
      at sites of pathology, they are frequently difficult to establish as stable T
      cell clones. Furthermore, in general, larger peptides in higher concentrations
      are required to stimulate CD4+ T cells than CD8+ T cells, which makes some of the
      techniques developed to identify CD8+ T cell Ags impractical. To circumvent some
      of these problems, we developed a model system consisting of two parts. The first
      part involves the construction of an indicator T cell hybridoma expressing a
      chimeric TCR comprised of murine constant regions and human variable regions
      specific for influenza hemagglutinin 307-319 presented by DR4. The second part
      consists of a library of fibroblasts each expressing multiple peptides as amino
      terminal covalent extensions of the beta-chain of HLA-DR4 (DRA1*0101, DRB1*0401).
      Using this model system, we screened approximately 100, 000 peptides and
      identified three novel peptides stimulatory for the HA1.7 TCR. While there is
      some convergence at residues known to be important for T cell recognition, all
      three peptides differ markedly from each other and bear little resemblance to
      wild-type hemagglutinin 307-319.

PMID- 10925288
TI  - The cleavage of two C1s subunits by a single active C1r reveals substantial
      flexibility of the C1s-C1r-C1r-C1s tetramer in the C1 complex.
AB  - The activation of the C1s-C1r-C1r-C1s tetramer in the C1 complex, which involves
      the cleavage of an Arg-Ile bond in the catalytic domains of the subcomponents, is
      a two-step process. First, the autolytic activation of C1r takes place, then
      activated C1r cleaves zymogen C1s. The Arg463Gln mutant of C1r (C1rQI) is
      stabilized in the zymogen form. This mutant was used to form a C1q-(C1s-C1rQI-C1r
      C1s) heteropentamer to study the relative position of the C1r and C1s subunits in
      the C1 complex. After triggering the C1 by IgG-Sepharose, both C1s subunits are
      cleaved by the single proteolytically active C1r subunit in the C1s-C1rQI-C1r-C1s
      tetramer. This finding indicates that the tetramer is flexible enough to adopt
      different conformations within the C1 complex during the activation process,
      enabling the single active C1r to cleave both C1s, the neighboring and the
      sequentially distant one.

PMID- 10925289
TI  - Human lymphocyte-specific protein 1, the protein overexpressed in neutrophil
      actin dysfunction with 47-kDa and 89-kDa protein abnormalities (NAD 47/89), has
      multiple F-actin binding domains.
AB  - Human lymphocyte-specific protein 1 (LSP1) is an F-actin binding protein, which
      has an acidic N-terminal half and a basic C-terminal half. In the basic C
      terminal half, there are amino acid sequences highly homologous to the actin
      binding domains of two known F-actin binding proteins: caldesmon and the villin
      headpieces (CI, CII, VI, VII). However, the exact numbers and locations of the F
      actin binding domains within LSP1 are not clearly defined. In this report, we
      utilized 125I-labeled F-actin ligand blotting and high-speed F-actin
      cosedimentation assays to analyze the F-actin binding properties of truncated
      LSP1 peptides and to define the F-actin binding domains. Results show that LSP1
      has at least three and potentially a fourth F-actin binding domain. All F-actin
      binding domains are located in the basic C-terminal half and correspond to the
      caldesmon and villin headpiece homologous regions. LSP1 181-245 and LSP1 246-295,
      containing sequences homologous to caldesmon F-actin binding site I and II,
      respectively (CI, CII), binds F-actin; similarly, LSP1 306-339 can bind F-actin
      and contains two inseparable villin headpiece-like F-actin binding domains (VI,
      VII). Although LSP1 1-305, which does not contain VI and VII regions, retains F
      actin binding activity, its binding affinity for F-actin is much weaker than that
      of full-length LSP1. Site-directed mutagenesis of the basic amino acids in the
      KRYK (VI) or KYEK (VII) sequences to acidic amino acids create mutants that bind
      F-actin with lower affinity than full-length wild-type LSP1. High KCl
      concentrations decrease full-length LSP1 binding to F-actin, suggesting the
      affinity between LSP1 and F-actin is mainly through electrostatic interaction.

PMID- 10925290
TI  - The MHC class II molecule I-Ag7 exists in alternate conformations that are
      peptide dependent.
AB  - Insulin-dependent diabetes mellitus is an autoimmune disease that is genetically
      linked to the HLA class II molecule DQ in humans and to MHC I-Ag7 in nonobese
      diabetic mice. The I-Ag7 beta-chain is unique and contains multiple
      polymorphisms, at least one of which is shared with DQ alleles linked to insulin
      dependent diabetes mellitus. This polymorphism occurs at position 57 in the beta
      chain, in which aspartic acid is mutated to a serine, a change that results in
      the loss of an interchain salt bridge between alphaArg76 and betaAsp57 at the
      periphery of the peptide binding groove. Using mAbs we have identified
      alternative conformations of I-Ag7 class II molecules. By using an invariant
      chain construct with various peptides engineered into the class II-associated
      invariant chain peptide (CLIP) region we have found that formation of these
      conformations is dependent on the peptide occupying the binding groove. Blocking
      studies with these Abs indicate that these conformations are present at the cell
      surface and are capable of interactions with TCRs that result in T cell
      activation.

PMID- 10925291
TI  - Essential role of CD8 palmitoylation in CD8 coreceptor function.
AB  - To investigate the molecular basis that makes heterodimeric CD8alphabeta a more
      efficient coreceptor than homodimeric CD8alphaalpha, we used various CD8
      transfectants of T1.4 T cell hybridomas, which are specific for H-2Kd, and a
      photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS
      252-260 (SYIPSAEKI). We demonstrate that CD8 is palmitoylated at the cytoplasmic
      tail of CD8beta and that this allows partitioning of CD8alphabeta, but not of
      CD8alphaalpha, in lipid rafts. Localization of CD8 in rafts is crucial for its
      coreceptor function. First, association of CD8 with the src kinase p56lck takes
      place nearly exclusively in rafts, mainly due to increased concentration of both
      components in this compartment. Deletion of the cytoplasmic domain of CD8beta
      abrogated localization of CD8 in rafts and association with p56lck. Second, CD8
      mediated cross-linking of p56lck by multimeric Kd-peptide complexes or by anti
      CD8 Ab results in p56lck activation in rafts, from which the abundant phosphatase
      CD45 is excluded. Third, CD8-associated activated p56lck phosphorylates CD3zeta
      in rafts and hence induces TCR signaling and T cell activation. This study shows
      that palmitoylation of CD8beta is required for efficient CD8 coreceptor function,
      mainly because it dramatically increases CD8 association with p56lck and CD8
      mediated activation of p56lck in lipid rafts.

PMID- 10925292
TI  - Impaired CTL recognition of cells latently infected with Kaposi's sarcoma
      associated herpes virus.
AB  - Kaposi's sarcoma-associated herpes virus (KSHV) is a recently identified human
      gamma2-herpesvirus associated with Kaposi's sarcoma, primary effusion lymphoma,
      and Castleman's disease. We reasoned that CTL responses may provide host defense
      against this virus, and consequently, KSHV may have evolved strategies to evade
      the CTL-mediated immune surveillance. In this study six B cell lines latently
      infected with KSHV were found to express reduced levels of HLA class I surface
      molecules compared with B cell lines transformed by the related gamma-herpesvirus
      EBV. KSHV-infected cells also required higher concentrations of soluble peptides
      to induce efficient CTL-mediated lysis than control cell lines and were unable to
      process and/or present intracellularly expressed Ag. Incubation of the KSHV
      infected cell lines with high concentrations of soluble HLA class I binding
      peptides did not restore the deficient HLA class I surface expression. To assess
      the underlying mechanisms of these phenomena, TAP-1 and TAP-2 gene expression was
      analyzed. While no attenuation in TAP-2 expression was observed, TAP-1 expression
      was significantly reduced in all KSHV cell lines compared with that in controls.
      These results indicate that KSHV can modulate HLA class I-restricted Ag
      presentation to CTL, which may allow latently infected cells to escape CTL
      recognition and persist in the infected host.

PMID- 10925293
TI  - Recombinant attenuated Toxoplasma gondii expressing the Plasmodium yoelii
      circumsporozoite protein provides highly effective priming for CD8+ T cell
      dependent protective immunity against malaria.
AB  - The protozoan parasite Toxoplasma gondii elicits strong cell-mediated immunity
      against itself as well as nonspecific resistance against other pathogens and
      tumors. For this reason, we asked whether recombinant Toxoplasma could be
      utilized as an effective vaccine vehicle for inducing immunity against
      heterologous microbial infections. The circumsporozoite protein (PyCSP) of
      Plasmodium yoelii was engineered into a T. gondii temperature-sensitive strain
      (ts-4), a mutant that induces complete protection against virulent Toxoplasma
      challenge. When administered to mice in a single dose, a recombinant ts-4 (CSC3)
      that both secretes and expresses surface PyCSP induced strong anti-CSP Ab
      responses, with an isotype distribution pattern similar to that stimulated by the
      T. gondii carrier. When challenged with P. yoelii sporozoites during the first
      month after CSC3 vaccination, these animals displayed substantial levels of
      nonspecific resistance attributable entirely to the T. gondii carrier.
      Nevertheless, after the nonspecific protection had waned, high levels (up to 79%)
      of specific immunity against sporozoite challenge were achieved by boosting the
      animals with recombinant vaccinia virus expressing PyCSP. These CSC3-primed PyCSP
      vaccinia-boosted mice displayed high frequencies of splenic PyCSP-specific IFN
      gamma-producing cells, as well as CD8+ T cell-dependent cytolytic activity. In
      vivo depletion of CD8+ lymphocytes at the time of challenge completely ablated
      protective immunity in the T. gondii-primed/vaccinia-boosted animals, while
      neutralization of IFN-gamma or IL-12 caused a partial but significant reduction
      in resistance. Together these findings establish the efficacy of recombinant
      attenuated Toxoplasma as a vaccine vehicle for priming CD8+-dependent cell
      mediated immunity.

PMID- 10925294
TI  - Distinct pathways of mannan-binding lectin (MBL)- and C1-complex autoactivation
      revealed by reconstitution of MBL with recombinant MBL-associated serine protease
      2.
AB  - Mannan-binding lectin (MBL) plays a pivotal role in innate immunity by activating
      complement after binding carbohydrate moieties on pathogenic bacteria and
      viruses. Structural similarities shared by MBL and C1 complexes and by the MBL-
      and C1q-associated serine proteases, MBL-associated serine protease (MASP)-1 and
      MASP-2, and C1r and C1s, respectively, have led to the expectation that the
      pathways of complement activation by MBL and C1 complexes are likely to be very
      similar. We have expressed rMASP-2 and show that, whereas C1 complex
      autoactivation proceeds via a two-step mechanism requiring proteolytic activation
      of both C1r and C1s, reconstitution with MASP-2 alone is sufficient for
      complement activation by MBL. The results suggest that the catalytic activities
      of MASP-2 split between the two proteases of the C1 complex during the course of
      vertebrate complement evolution.

PMID- 10925295
TI  - Expression of intracellular IFN-gamma in HSV-1-specific CD8+ T cells identifies
      distinct responding subpopulations during the primary response to infection.
AB  - Cutaneous infection in the footpads of C57BL/6 mice with HSV-1 results in an
      accumulation of activated (CD44high CD25+) CD8+ T cells within the draining
      popliteal lymph node (PLN). These studies were undertaken to evaluate the
      frequency and phenotype of the CD8+ T cell population within the PLN, recognizing
      the single immunodominant HSV-1 epitope derived from the viral envelope
      glycoprotein, glycoprotein B (gB), using an intracellular IFN-gamma-staining
      assay. It revealed that approximately 6% of the CD8+ T cells were specific for
      the gB epitope. Phenotypic analysis of the IFN-gamma-producing gB-specific CD8+ T
      cells generated in the PLN during the course of the acute infection expressed the
      CD44high CD25+ phenotype on days 3-5 postinfection. Surprisingly, IFN-gamma
      producing CD8+ T cells expressed the CD44high CD25- phenotype on days 5-8
      postinfection, in contrast to expectations for a CD8+ effector T cell. IFN-gamma
      producing CD25- CD8+ T cells were detected in the PLN on day 21 postinfection,
      long after infectious virus had been cleared. Throughout the response, the spleen
      was found to be the major reservoir of gB-specific CD8+ T cells, even during the
      peak of the response. In contrast to the gB-specific CD8+ T cell population
      within the PLN, the entire gB-specific CD8+ T cell population within the spleen
      was CD25-. Collectively, these results suggest the generation of subpopulations
      of virus-specific CD8+ T cells, distinguished by the expression of CD25, during
      the acute phase of the primary response to a localized viral infection.

PMID- 10925296
TI  - Enhanced antiviral and opsonic activity of a human mannose-binding lectin and
      surfactant protein D chimera.
AB  - The carbohydrate recognition domains (CRDs) of human serum mannose-binding lectin
      (MBL) and pulmonary surfactant protein D (SP-D) have distinctive monosaccharide
      binding properties, and their N-terminal and collagen domains have very different
      quaternary structures. We produced a chimeric protein containing the N terminus
      and collagen domain of human SP-D and the neck region and CRD of human MBL (SP
      D/MBLneck+CRD) to create a novel human collectin. The chimera bound to influenza
      A virus (IAV), inhibited IAV hemagglutination activity and infectivity, and
      induced aggregation of viral particles to a much greater extent than MBL.
      Furthermore, SP-D/MBLneck+CRD caused much greater increases in neutrophil uptake
      of, and respiratory burst responses to, IAV than MBL. These results indicate that
      pathogen interactions mediated by the MBL CRD are strongly influenced by the N
      terminal and collagen-domain backbone to which it is attached. The presence of
      the CRD of MBL in the chimera resulted in altered monosaccharide binding
      properties compared with SP-D. As a result, the chimera caused greater
      aggregation and neutralization of IAV than SP-D. Distinctive functional
      properties of collectin collagenous domains and CRDs can be exploited to generate
      novel human collectins with potential for therapy of influenza.

PMID- 10925297
TI  - Regulation of neutrophil adhesion by pituitary growth hormone accompanies
      tyrosine phosphorylation of Jak2, p125FAK, and paxillin.
AB  - Neutrophil adhesion is fundamentally important during the onset of inflammatory
      responses. The adhesion signaling pathways control neutrophil arrest and
      extravasation and influence neutrophil shape and function at sites of
      inflammation. In the present study the intracellular signaling pathways for the
      adhesion of human neutrophils by pituitary growth hormone (GH) were examined.
      Pituitary GH triggered the tyrosine phosphorylation of Janus kinase 2 (Jak2) and
      STAT3 in neutrophils. In addition, pituitary GH treatment resulted in the
      morphological changes and the tyrosine phosphorylation of focal adhesion kinase
      (p125FAK) and paxillin. Preincubation with genistein, a tyrosine kinase
      inhibitor, blocked the GH-stimulated adhesion and Jak2, STAT3, p125FAK, and
      paxillin phosphorylation. Confocal microscopy revealed that pituitary GH
      stimulates the focal localization of p125FAK, paxillin, phosphotyrosine, and
      filamentous actin filament into the membrane rufflings and uropods of human
      neutrophils. Immunoprecipitation experiments revealed a physical association of
      Jak2 with p125FAK via STAT3 in vivo. Also an in vitro kinase assay showed an
      augmentation of p125FAK autophosphorylation as a result of pituitary GH
      treatment. These results suggest that pituitary GH modulates neutrophil adhesion
      through tyrosine phosphorylation of Jak2, p125FAK, and paxillin and actin
      polymerization.

PMID- 10925298
TI  - Deficient in vitro and in vivo phagocytosis of apoptotic T cells by resident
      murine alveolar macrophages.
AB  - Apoptotic lymphocytes are readily identified in murine lungs, both during the
      response to particulate Ag and in normal mice. Because apoptotic lymphocytes are
      seldom detected in other organs, we hypothesized that alveolar macrophages
      (AMphi) clear apoptotic lymphocytes poorly. To test this hypothesis, we compared
      in vitro phagocytosis of apoptotic thymocytes by resident AMphi and peritoneal
      macrophages (PMphi) from normal C57BL/6 mice. AMphi were deficient relative to
      PMphi both in percentage containing apoptotic thymocytes (19.1 +/- 1% vs 96 +/-
      2.6% positive) and in phagocytic index (0.23 +/- 0.02 vs 4.2 +/- 0.67). This
      deficiency was not due to kinetic differences, was seen with six other inbred
      mouse strains, and was not observed using carboxylate-modified polystyrene
      microbeads. Annexin V blockade indicated that both Mphi types cleared apoptotic T
      cells by a mechanism involving phosphatidylserine expression. By contrast,
      neither mAb blockade of a variety of receptors (CD11b, CD29, CD51, and CD61)
      known to be involved in clearance of apoptotic cells, nor the tetrapeptide RGDS
      (arginine-glycine-aspartic acid-serine) blocked ingestion by either type of
      macrophage. To confirm these studies, apoptotic thymocytes were given
      intratracheally or i.p. to normal mice, and then AMphi or PMphi were recovered 30
      240 min later. Ingestion of apoptotic thymocytes by AMphi in vivo was
      significantly decreased at all times. Defective ingestion of apoptotic
      lymphocytes may preserve AMphi capacity to produce proinflammatory cytokines in
      host defense, but could contribute to development of autoimmunity by failing to
      eliminate nucleosomes.

PMID- 10925299
TI  - The involvement of tyrosine kinases, cyclic AMP/protein kinase A, and p38 mitogen
      activated protein kinase in IL-13-mediated arginase I induction in macrophages:
      its implications in IL-13-inhibited nitric oxide production.
AB  - In macrophages, L-arginine can be used by NO synthase and arginase to form NO and
      urea, respectively. Therefore, activation of arginase may be an effective
      mechanism for regulating NO production in macrophages through substrate
      competition. Here, we examined whether IL-13 up-regulates arginase and thus
      reduces NO production from LPS-activated macrophages. The signaling molecules
      involved in IL-13-induced arginase activation were also determined. Results
      showed that IL-13 increased arginase activity through de novo synthesis of the
      arginase I mRNA and protein. The activation of arginase was preceded by a
      transient increase in intracellular cAMP, tyrosine kinase phosphorylation, and
      p38 mitogen-activated protein kinase (MAPK) activation. Exogenous cAMP also
      increased arginase activity and enhanced the effect of IL-13 on arginase
      induction. The induction of arginase was abolished by a protein kinase A (PKA)
      inhibitor, KT5720, and was down-regulated by tyrosine kinase inhibitors and a p38
      MAPK inhibitor, SB203580. However, inhibition of p38 MAPK had no effect on either
      the IL-13-increased intracellular cAMP or the exogenous cAMP-induced arginase
      activation, suggesting that p38 MAPK signaling is parallel to the cAMP/PKA
      pathway. Furthermore, the induction of arginase was insensitive to the protein
      kinase C and p44/p42 MAPK kinase inhibitors. Finally, IL-13 significantly
      inhibited NO production from LPS-activated macrophages, and this effect was
      reversed by an arginase inhibitor, L-norvaline. Together, these data demonstrate
      for the first time that IL-13 down-regulates NO production through arginase
      induction via cAMP/PKA, tyrosine kinase, and p38 MAPK signalings and underline
      the importance of arginase in the immunosuppressive activity of IL-13 in
      activated macrophages.

PMID- 10925300
TI  - E-selectin-dependent signaling via the mitogen-activated protein kinase pathway
      in vascular endothelial cells.
AB  - E-selectin, a cytokine-inducible adhesion molecule, supports rolling and stable
      arrest of leukocytes on activated vascular endothelium. Previous studies have
      suggested that this transmembrane protein can also transduce signals into the
      endothelial cell. We now demonstrate activation of the mitogen-activated protein
      kinase (MAPK) signaling cascade in cultured HUVEC in response to E-selectin
      dependent leukocyte adhesion and Ab-mediated cross-linking of cell surface E
      selectin. Adhesion of increasing numbers of HL60 cells to IL-1beta-activated
      HUVEC stimulated robust increases in MAPK activity that were abrogated by an E
      selectin blocking Ab. Cross-linking of cell surface E-selectin with Abs, as a
      mimic of multivalent ligand engagement, strongly stimulated MAPK/extracellular
      signal-related kinase (ERK) kinase (MEK)-dependent MAPK activation and
      concomitant up-regulation of mRNA for c-fos, an immediate early response gene,
      whereas Ab cross-linking of HLA class I molecules (present at comparable density)
      failed to do so. Coimmunoprecipitation documented Ras, Raf-1 and, phospho-MEK
      complex formation. Unactivated HUVEC transduced with a full-length adenoviral E
      selectin construct also exhibited cross-link-induced MAPK activation,
      macromolecular complex formation, and c-fos up-regulation, whereas HUVEC
      transduced with a cytoplasmic domain deletion mutant failed to respond. These
      observations indicate that E-selectin can transduce an activating stimulus via
      the MAPK cascade into the endothelial cell during leukocyte adhesion.

PMID- 10925301
TI  - Oncostatin M stimulates the growth of dermal fibroblasts via a mitogen-activated
      protein kinase-dependent pathway.
AB  - Oncostatin M (OSM), a member of the hemopoietic cytokine family, has been
      implicated in the process of fibrosis and dermal wound healing. As a part of an
      ongoing study of the mechanisms of fibrosis and dermal wound healing, we have
      investigated the mechanism of the growth regulation of dermal fibroblasts by OSM.
      OSM stimulates the mitogenesis of dermal fibroblasts in a dose-dependent manner.
      This effect was completely blocked by anti-OSM IgG, but not by anti-IL-6 IgG.
      Furthermore, OSM induction was abolished by genistein, a tyrosine kinase
      inhibitor, or by PD98059, a specific mitogen-activated protein (MAP) kinase
      pathway inhibitor, but not by calphostin C, a protein kinase C inhibitor.
      Immunoblotting analysis using a specific Ab against phosphorylated MAP kinase
      (Thr202/Tyr204) showed that OSM induces phosphorylation of MAP kinase in dermal
      fibroblasts. Furthermore, transient transfection of the dominant-negative mutant
      MAP kinase into dermal fibroblasts abolished the OSM induction. These results
      strongly suggest that OSM stimulates the growth of dermal fibroblasts via a MAP
      kinase-dependent pathway.

PMID- 10925302
TI  - Human galectin-3 is a novel chemoattractant for monocytes and macrophages.
AB  - Galectin-3 is a beta-galactoside-binding protein implicated in diverse biological
      processes. We found that galectin-3 induced human monocyte migration in vitro in
      a dose-dependent manner, and it was chemotactic at high concentrations (1.0
      microM) but chemokinetic at low concentrations (10-100 nM). Galectin-3-induced
      monocyte migration was inhibited by its specific mAb and was blocked by lactose
      and a C-terminal domain fragment of the protein, indicating that both the N
      terminal and C-terminal domains of galectin-3 are involved in this activity.
      Pertussis toxin (PTX) almost completely blocked monocyte migration induced by
      high concentrations of galectin-3. Galectin-3 caused a Ca2+ influx in monocytes
      at high, but not low, concentrations, and both lactose and PTX inhibited this
      response. There was no cross-desensitization between galectin-3 and any of the
      monocyte-reactive chemokines examined, including monocyte chemotactic protein-1,
      macrophage inflammatory protein-1alpha, and stromal cell-derived factor-1alpha.
      Cultured human macrophages and alveolar macrophages also migrated toward galectin
      3, but not monocyte chemotactic protein-1. Finally, galectin-3 was found to cause
      monocyte accumulation in vivo in mouse air pouches. These results indicate that
      galectin-3 is a novel chemoattractant for monocytes and macrophages and suggest
      that the effect is mediated at least in part through a PTX-sensitive (G protein
      coupled) pathway.

PMID- 10925303
TI  - TNF-Induced shedding of TNF receptors in human polymorphonuclear leukocytes: role
      of the 55-kDa TNF receptor and involvement of a membrane-bound and non-matrix
      metalloproteinase.
AB  - A down-modulation of both the 55-kDa (TNF-R55) and the 75-kDa (TNF-R75) TNF
      receptors is observed in neutrophils exposed to a variety of stimuli. Proteolytic
      cleavage of the extracellular region of both receptors (shedding) and, with TNF,
      internalization of TNF-R55 and shedding of TNF-R75 are the proposed mechanisms.
      We have characterized the TNF-induced shedding of TNF receptors in neutrophils
      and determined the nature of the involved proteinase. Neutrophils exposed to TNF
      release both TNF receptors. A release of TNF receptors comparable to that
      observed with TNF was induced with TNF-R55-specific reagents (mAbs and a mutant
      of TNF) but not with the corresponding TNF-R75-specific reagents. A hydroxamic
      acid compound (KB8301) almost completely inhibited shedding of TNF-R55 and to a
      lesser degree shedding of TNF-R75. KB8301 also inhibited FMLP-induced shedding to
      a similar extent. Shedding was also inhibited by 1,10-phenanthroline, but this
      effect was considered nonspecific as the compound, at variance with KB8301,
      almost completely inhibited TNF and FMLP-induced PMN activation.
      Diisopropylfluorophosphate partially inhibited shedding of TNF-R75, suggesting
      the contribution of a serine proteinase to the release of this receptor. Shedding
      activity was not affected by matrix metalloproteinases inhibitors nor was it
      released in the supernatants of FMLP-stimulated neutrophils. These results
      suggest that TNF induces release of its receptors, that such a release is
      mediated via TNF-R55, and that a membrane-bound and non-matrix metalloproteinase
      is involved in the process. The possibility that ADAM-17, which we show to be
      expressed in neutrophils, might be the involved proteinase is discussed.

PMID- 10925304
TI  - Colitis induced by enteric bacterial antigen-specific CD4+ T cells requires CD40
      CD40 ligand interactions for a sustained increase in mucosal IL-12.
AB  - C3H/HeJBir is a mouse substrain that is highly susceptible to colitis. Their CD4+
      T cells react to Ags of the commensal enteric bacteria, and the latter can
      mediate colitis when activated by these Ags and transferred to histocompatible
      scid recipients. In this study, multiple long-term C3H/HeJBir CD4+ T cell (Bir)
      lines reactive to commensal enteric bacterial Ags have been generated. All these
      were Ag specific, pauciclonal, and Th1 predominant; most induced colitis
      uniformly after transfer to scid recipients. Lesions were focal and marked by
      increased expression of IL-12p40 and IFN-gamma mRNA and protein. Pathogenic Bir T
      cell lines expressed CD40 ligand (CD40L) when cultured with Ag-pulsed APCs in
      vitro. Production of IL-12 was also increased in such cultures, an effect that
      was Ag- and T cell-dependent and required costimulation by CD40, but not by B7.
      The two Bir T cell lines that did not induce lesions after transfer failed to
      significantly express CD40L or increase IL-12 when cultured with Ag-pulsed APCs.
      Administration of anti-CD40L blocked disease expression induced by pathogenic T
      cells. We conclude that interactions in the colon mucosa between CD40L-expressing
      Bir Th1 cells with APCs endogenously loaded with commensal bacterial Ags are
      critical for sustained increases in local IL-12 production and progression to
      colitis.

PMID- 10925305
TI  - Requirements for C5a receptor-mediated IL-4 and IL-13 production and leukotriene
      C4 generation in human basophils.
AB  - Anaphylatoxin derived from the fifth complement component (C5a) in the presence
      of IL-3 induces continuous leukotriene C4 generation and IL-4 and IL-13
      expression in human basophils for a period of 16-18 h. This indicates that the G
      protein-coupled C5a receptor (C5aR) can induce long-lasting cellular responses.
      Using anti-N-terminal C5aR Abs, C-terminal C5a hexapeptide analogs, and pertussis
      toxin, we demonstrate that the putative activation site of the C5aR is both
      necessary and sufficient for these late cellular responses. Furthermore,
      continuous pertussis toxin-sensitive G protein-coupled receptor activation and
      receptor-ligand interaction is ongoing and required during the entire period of
      product release. However, the late basophil responses have a more stringent
      requirement for optimal receptor activation. Leukotriene C4 generation appears to
      be influenced mostly by the way the receptor is activated, because the most
      active hexapeptide is a superagonist for this response. By contrast, C5adesarg,
      lacking the C-terminal arginine, induces minimal lipid mediator formation but is
      fully active to induce IL-4 production and is even a superagonist for IL-13
      release. Nevertheless, IL-4/IL-13 synthesis in response to C5adesarg could be
      blocked by both C-terminal antagonistic peptide as well as anti-N-terminal C5aR
      Abs, indicating only minor differences of ligand-receptor interactions between
      C5a and C5adesarg. Taken together, our data demonstrate that long-lasting and
      continuous signaling occurs through a limited activation domain of the C5aR,
      which can differentially promote separate basophil functions.

PMID- 10925306
TI  - Requirement of hydrogen peroxide generation in TGF-beta 1 signal transduction in
      human lung fibroblast cells: involvement of hydrogen peroxide and Ca2+ in TGF
      beta 1-induced IL-6 expression.
AB  - Stimulation of human lung fibroblast cells with TGF-beta1 resulted in a transient
      burst of reactive oxygen species with maximal increase at 5 min after treatment.
      This reactive oxygen species increase was inhibited by the antioxidant, N-acetyl
      l -cysteine (NAC). TGF-beta1 treatment stimulated IL-6 gene expression and
      protein synthesis in human lung fibroblast cells. Antioxidants including NAC,
      glutathione, and catalase reduced TGF-beta1-induced IL-6 gene expression, and
      direct H2O2 treatment induced IL-6 expression in a dose-dependent manner. NAC
      also reduced TGF-beta1-induced AP-1 binding activity, which is involved in IL-6
      gene expression. It has been reported that Ca2+ influx is stimulated by TGF-beta1
      treatment. EGTA suppressed TGF-beta1- or H2O2-induced IL-6 expression, and
      ionomycin increased IL-6 expression, with simultaneously modulating AP-1 activity
      in the same pattern. PD98059, an inhibitor of mitogen-activated protein kinase
      (MAPK) kinase/extracellular signal-related kinase kinase 1, suppressed TGF-beta1-
      or H2O2-induced IL-6 and AP-1 activation. In addition, TGF-beta1 or H2O2
      increased MAPK activity which was reduced by EGTA and NAC, suggesting that MAPK
      is involved in TGF-beta1-induced IL-6 expression. Taken together, these results
      indicate that TGF-beta1 induces a transient increase of intracellular H2O2
      production, which regulates downstream events such as Ca2+ influx, MAPK, and AP-1
      activation and IL-6 gene expression.

PMID- 10925307
TI  - The differential role of extracellular signal-regulated kinases and p38 mitogen
      activated protein kinase in eosinophil functions.
AB  - The activation of eosinophils by cytokines is a major event in the pathogenesis
      of allergic diseases. We have investigated the activation of mitogen-activated
      protein (MAP) kinases and their functional relevance in eosinophil
      differentiation, survival, degranulation, and cytokine production. IL-5 induced
      phosphorylation and activation of extracellular signal-regulated kinases (ERK)
      and p38 MAP kinases in eosinophils. PD98059, a MAP/ERK kinase inhibitor, blocked
      phosphorylation of ERK1/2 in a dose-dependent manner. SB202190, a p38 inhibitor,
      blocked p38-dependent phosphorylation of activating transcription factor-2. To
      study the importance of the MAP kinases on eosinophil differentiation, we
      cultured mouse bone marrow cells with IL-3 and IL-5 in the presence of the
      inhibitors. SB202190 dramatically inhibited eosinophil differentiation by 71%.
      PD98059 was less potent and reduced eosinophil differentiation by 28%. Both
      inhibitors marginally inhibited eosinophil survival only at the highest doses.
      Prolonged incubation of eosinophils with IL-5 induced significant eosinophil
      derived neurotoxin release. Both PD98059 and SB202190 nearly completely inhibited
      (87% and 100% inhibition, respectively) IL-5-stimulated eosinophil-derived
      neurotoxin release in a dose-dependent manner. Next, we examined the effect of
      the MAP kinase inhibitors on eosinophil production of the cytokine macrophage
      inflammatory protein (MIP)-1alpha. PD98059 blocked C5a- but not ionomycin-induced
      MIP-1alpha production (59% inhibition at 50 microM concentration). In contrast,
      SB202190 nearly completely inhibited (99%) C5a-induced MIP-1alpha production.
      Further, it blocked ionomycin-stimulated production by 66%. Our results suggest
      that both p38 and ERK1/2 MAP kinases play an important role in eosinophil
      differentiation, cytokine production, and degranulation. The p38 MAP kinase plays
      a greater role than ERK1/2 in eosinophil differentiation and cytokine production.

PMID- 10925308
TI  - Inducible expression of a Th2-type CC chemokine thymus- and activation-regulated
      chemokine by human bronchial epithelial cells.
AB  - CCR4 is now known to be selectively expressed in Th2 cells. Since the bronchial
      epithelium is recognized as an important source of mediators fundamental to the
      manifestation of respiratory allergic inflammation, we studied the expression of
      two functional ligands for CCR4, i.e., macrophage-derived chemokine (MDC) and
      thymus- and activation-regulated chemokine (TARC), in bronchial epithelial cells.
      The bronchial epithelium of asthmatics and normal subjects expressed TARC
      protein, and the asthmatics showed more intense expression than the normal
      subjects. On the other hand, MDC expression was only weakly detected in the
      asthmatics, but the intensity was not significantly different from that of normal
      subjects. Combination of TNF-alpha and IL-4 induced expression of TARC protein
      and mRNA in bronchial epithelial A549 cells, which was slightly up-regulated by
      IFN-gamma. The enhancement by IFN-gamma was more pronounced in bronchial
      epithelial BEAS-2B cells, and a maximum production occurred with combination of
      TNF-alpha, IL-4, and IFN-gamma. On the other hand, MDC was essentially not
      expressed in any of the cultures. Furthermore, expressions of TARC protein and
      mRNA were almost completely inhibited by glucocorticoids. These results indicate
      that the airway epithelium represents an important source of TARC, which
      potentially plays a role via a paracrine mechanism in the development of allergic
      respiratory diseases. Furthermore, the beneficial effect of inhaled
      glucocorticoids on asthma may be at least in part due to their direct inhibitory
      effect on TARC generation by the bronchial epithelium.

PMID- 10925309
TI  - Proinflammatory and Th2-derived cytokines modulate CD40-mediated expression of
      inflammatory mediators in airway epithelia: implications for the role of
      epithelial CD40 in airway inflammation.
AB  - Cytokines produced by activated macrophages and Th2 cells within the lung play a
      key role in asthma-associated airway inflammation. Additionally, recent studies
      suggest that the molecule CD40 modulates lung immune responses. Because airway
      epithelial cells can act as immune effector cells through the expression of
      inflammatory mediators, the epithelium is now considered important in the
      generation of asthma-associated inflammation. Therefore, the goal of the present
      study was to examine the effects of proinflammatory and Th2-derived cytokines on
      the function of CD40 in airway epithelia. The results show that airway epithelial
      cells express CD40 and that engagement of epithelial CD40 induces a significant
      increase in expression of the chemokines RANTES, monocyte chemoattractant protein
      (MCP-1), and IL-8 and the adhesion molecule ICAM-1. Cross-linking epithelial CD40
      had no effect on expression of the adhesion molecule VCAM-1. The proinflammatory
      cytokines TNF-alpha and IL-1beta and the Th2-derived cytokines IL-4 and IL-13
      modulated the positive effects of CD40 engagement on inflammatory mediator
      expression in airway epithelial cells. Importantly, CD40 ligation enhanced the
      sensitivity of airway epithelial cells to the effects of TNF-alpha and/or IL
      1beta on expression of RANTES, MCP-1, IL-8, and VCAM-1. In contrast, neither IL-4
      nor IL-13 modified the effects of CD40 engagement on the expression of RANTES,
      MCP-1, IL-8, or VCAM-1; however, both IL-4 and IL-13 attenuated the effects of
      CD40 cross-linking on ICAM-1 expression. Together, these findings suggest that
      interactions between CD40-responsive airway epithelial cells and CD40 ligand+
      leukocytes, such as activated T cells, eosinophils, and mast cells, modulate
      asthma-associated airway inflammation.

PMID- 10925310
TI  - IL-11 selectively inhibits aeroallergen-induced pulmonary eosinophilia and Th2
      cytokine production.
AB  - IL-11 is a pleiotropic cytokine that induces tissue remodeling with subepithelial
      fibrosis when expressed in the airway. Its effects on the Th2-dominated airway
      inflammation that is characteristic of asthma, however, are poorly understood. To
      characterize the effects of IL-11 on Th2 tissue inflammation, we compared the
      inflammatory responses elicited by OVA in sensitized mice in which IL-11 is
      overexpressed in a lung-specific fashion (CC10-IL-11) with that in transgene-
      wild-type littermate controls. Transgene- and CC10-IL-11 transgene+ mice had
      comparable levels of circulating Ag-specific IgE after sensitization. OVA
      challenge of sensitized transgene- mice caused airway and parenchymal
      eosinophilic inflammation, Th2 cell accumulation, and mucus hypersecretion with
      mucus metaplasia. Exaggerated levels of immunoreactive endothelial cell VCAM-1,
      mucin (Muc) 5ac gene expression and bronchoalveolar lavage and lung IL-4, IL-5,
      and IL-13 protein and mRNA were also noted. In contrast, OVA challenge in CC10-IL
      11 animals elicited impressively lower levels of tissue and bronchoalveolar
      lavage inflammation, eosinophilia, and Th2 cell accumulation, and significantly
      lower levels of VCAM-1 and IL-4, IL-5, and IL-13 mRNA and protein. IL-11 did not
      cause a comparable decrease in mucus hypersecretion, Muc 5ac gene expression, or
      the level of expression of RANTES, monocyte chemoattractant protein-2, or
      monocyte chemoattractant protein-3. In addition, IL-11 did not augment IFN-gamma
      production demonstrating that the inhibitory effects of IL-11 were not due to a
      shift toward Th1 inflammation. These studies demonstrate that IL-11 selectively
      inhibits Ag-induced eosinophilia, Th2 inflammation, and VCAM-1 gene expression in
      pulmonary tissues.

PMID- 10925311
TI  - Central nervous system-initiated inflammation and neurotrophism in trauma: IL-1
      beta is required for the production of ciliary neurotrophic factor.
AB  - Injury to the CNS results in the production and accumulation of inflammatory
      cytokines within this tissue. The origin and role of inflammation within the CNS
      remains controversial. In this paper we demonstrate that an acute trauma to the
      mouse brain results in the rapid elevation of IL-1beta. This increase is
      detectable by 15 min after injury and significantly precedes the influx of
      leukocytes that occurs hours after. To confirm that IL-1beta up-regulation is
      initiated by cells within the CNS, in situ hybridization for cytokine transcript
      was combined with cell type immunohistochemistry. The results reveal parenchymal
      microglia to be the sole source of IL-1beta at 3 h postinjury. A role for CNS
      initiated inflammation was addressed by examining the expression of the
      neurotrophic factor, ciliary neurotrophic factor (CNTF). Analysis of their
      temporal relationship suggests the up-regulation of CNTF by IL-1beta, which was
      confirmed through three lines of evidence. First, the application of IL-1
      receptor antagonist into the lesion site attenuated the up-regulation of CNTF.
      Second, the examination of corticectomized animals genetically deficient for IL
      1beta found no CNTF up-regulation. Third, the lack of CNTF elevation in IL-1beta
      null mice was rescued through exogenous application of IL-1beta into the lesion
      site. These findings provide the first evidence of the requirement for IL-1beta
      in the production of CNTF following CNS trauma, and suggest that inflammation can
      have a beneficial impact on the regenerative capacity of the CNS.

PMID- 10925312
TI  - Inhibition of keratinocyte apoptosis by IL-15: a new parameter in the
      pathogenesis of psoriasis?
AB  - Keratinocytes (KC) are important source of and targets for several cytokines.
      Although KC express IL-15 mRNA, the functional effects of IL-15 on these
      epithelial cells remain to be dissected. Investigating primary human foreskin KC
      and HaCaT cells, we show here by semiquantitative RT-PCR and flow cytometric
      analysis that both translate IL-15 and IL-15R mRNA and express IL-15 and IL
      15Ralpha protein on the cell surface, suggesting that human KC can employ IL-15
      for juxtacrine signaling. While IL-15 exerted no significant effect on KC
      proliferation and IL-6 or IL-8 secretion, IL-15 inhibited both anti-Fas and
      methylcellulose-induced KC apoptosis in vitro. This is in line with the
      recognized potent anti-apoptotic effects of IL-15. IL-2, whose receptor shares
      two components with the IL-15R, failed to inhibit KC apoptosis. Together with the
      role of IL-15 in sustaining chronic immune reactions, this invited the question
      of whether a reduction of KC apoptosis by IL-15 may be involved in the
      pathogenesis of psoriasis, a chronic hyperproliferative inflammatory skin disease
      characterized by abnormally low KC apoptosis in the epidermis. Remarkably,
      compared with nonlesional psoriatic skin and skin of healthy volunteers, lesional
      psoriatic epidermis showed high IL-15 protein expression in the epidermis and
      enhanced binding activity for IL-15. Therefore, antagonizing the inhibitory
      effects of IL-15 on KC apoptosis deserves exploration as a novel therapeutic
      strategy in psoriasis management.

PMID- 10925313
TI  - Autoantigen-specific CD4+CD28low T cell subset prevents autoimmune exocrinopathy
      in murine Sjogren's syndrome.
AB  - Organ-specific autoimmune exocrinopathy resembling Sjogren's syndrome (SS) that
      spontaneously develops in NFS/sld mutant mice thymectomized 3 day after birth is
      dependent on Th1-type CD4+ T cells. We previously reported that a cleavage
      product of 120-kDa alpha-fodrin may be an important autoantigen in the
      pathogenesis of SS in both an animal model and the patients. We demonstrate that
      in an animal model of SS with overt exocrinopathy, a unique CD4+ T cell subset
      expressing CD28low is dramatically increased in spleen cells before the disease
      onset, but that the CD4+ T cells of diseased mice were virtually all CD28high. We
      found that the spleen cells in these mice before the disease onset showed a
      significant increase in autoantigen-specific T cell proliferation. Analysis of in
      vitro cytokine production by spleen cells indicated, before the disease onset,
      severely impaired production of IL-2 and IFN-gamma in the animal model, whereas
      high levels of IL-4 were observed. Expression of cytokine genes, including IL-4,
      IL-10, and TGF-beta, was detected in FACS-sorted CD4+CD28low T cells by RT-PCR
      analysis. Transfer of CD4+CD28low T cells into the animal model actually
      prevented the development of autoimmune lesions including autoantibody
      production. These results suggest that a CD4+CD28low T cell subset that is
      continuously activated by an organ-specific autoantigen may play a regulatory
      role in the development of organ-specific autoimmune disease in an animal model
      of SS.

PMID- 10925314
TI  - Monocyte tissue factor induction by activation of beta 2-glycoprotein-I-specific
      T lymphocytes is associated with thrombosis and fetal loss in patients with
      antiphospholipid antibodies.
AB  - Antiphospholipid (aPL) syndrome (APS) is characterized by thromboembolic events,
      thrombocytopenia, or recurrent miscarriage associated with aPL Abs with
      specificity for beta2-glycoprotein-I (beta2GPI). We recently reported that at
      least 44% of patients with the APS possess circulating type 1 (Th1) CD4+ T cells
      that proliferate and secrete IFN-gamma when stimulated with beta2GPI in vitro. In
      this study, we show that stimulation of PBMCs from 20 APS patients with beta2GPI
      induced substantial monocyte tissue factor (TF) (80 +/- 11 TF stimulation index
      (TF-SI)), whereas no induction was observed using PBMCs from 13 patients with aPL
      Abs without APS (6 +/- 1 TF-SI) or 7 normal and 7 autoimmune controls (5 +/- 1
      and 3 +/- 1 TF-SI, respectively) (p < 0.0001). TF induction on monocytes by
      beta2GPI was dose dependent and required CD4+ T lymphocytes and class II MHC
      molecules. Because monocyte TF induction by beta2GPI was observed in all patients
      with APS, but not in any patient with aPL Abs without APS, this response is a
      potentially useful predictor for APS in patients with aPL Abs, as well as
      providing mechanistic insight into thrombosis and fetal loss in these patients.

PMID- 10925315
TI  - Proteolytic cleavage of a self-antigen following xenobiotic-induced cell death
      produces a fragment with novel immunogenic properties.
AB  - The heavy metal mercury elicits a genetically restricted autoantibody response in
      mice that targets the nucleolar autoantigen fibrillarin. HgCl2-induced cell death
      of macrophages resulted in the proteolytic cleavage of fibrillarin. A prominent
      feature of mercury-induced cell death was the generation of a 19-kDa fragment of
      fibrillarin that was not found following apoptotic or nonapoptotic cell death
      induced by stimuli other than mercury. Proteolysis of fibrillarin lacking
      cysteines, and therefore unable to bind mercury, also produced the 19-kDa
      fragment, suggesting that a mercury-fibrillarin interaction was not necessary for
      the unique cleavage pattern of this self-Ag. In contrast to immunization with
      full-length fibrillarin, the 19-kDa fragment produced anti-fibrillarin Abs with
      some of the properties of the HgCl2-induced anti-fibrillarin response. We propose
      that cell death following exposure to an autoimmunity-inducing xenobiotic can
      lead to the generation of novel protein fragments that may serve as sources of
      antigenic determinants for self-reactive T lymphocytes.

PMID- 10925316
TI  - NF-kappa B as a central mediator in the induction of TGF-beta in monocytes from
      patients with idiopathic myelofibrosis: an inflammatory response beyond the realm
      of homeostasis.
AB  - Immune-mediated mechanisms have been implicated in the etiology of idiopathic
      bone marrow fibrosis (IMF). However, the mechanism remains poorly defined.
      Compared with healthy controls, IMF monocytes are overactivated, with increased
      production of TGF-beta and IL-1. TGF-beta is central to the progression of
      fibrosis in different organs. In the lung, fibrosis is associated with up
      regulation of TGF-beta-inducible genes. Because IL-1 and TGF-beta have pro- and
      antiinflammatory properties and neither appears to regulate the high levels of
      each other in IMF, we studied the mechanism of this paradigm. We focused on the
      role of RelA, a subunit of the transcription factor, NF-kappaB that is associated
      with inflammatory responses. We transiently knocked out RelA from IMF monocytes
      with antisense oligonucleotides and showed that RelA is central to IL-1 and TGF
      beta production and to the adhesion of IMF monocytes. Because the NF-kappaB
      family comprises subunits other than RelA, we used aspirin and sodium salicylate
      to inhibit kinases that activate NF-kappaB and showed effects similar to those of
      the RelA knockout system. It is unlikely that RelA could be interacting directly
      with the TGF-beta gene. Therefore, we determined its role in TGF-beta production
      and showed that exogenous IL-1 could induce TGF-beta and adherence of IMF
      monocytes despite the depletion of NF-kappaB. The results indicate that IL-1 is
      necessary for TGF-beta production in IMF monocytes, but NF-kappaB activation is
      required for the production of endogenous IL-1. Initial adhesion activates NF
      kappaB, which led to IL-1 production. Through autocrine means, IL-1 induces TGF
      beta production. In total, these reactions maintain overactivation of IMF
      monocytes.

PMID- 10925317
TI  - CD4 and CD8 T cells have redundant but not identical roles in virus-induced
      demyelination.
AB  - A chronic demyelinating disease results from murine infection with the
      neurotropic strain JHM of mouse hepatitis virus (MHV-JHM). Demyelination is
      largely immune mediated. In this study, the individual roles of CD4 and CD8 T
      cells in MHV-induced demyelination were investigated using recombination
      activating gene 1-/- (RAG1-/-) mice infected with an attenuated strain of MHV
      JHM. These animals develop demyelination only after adoptive transfer of
      splenocytes from mice previously immunized to MHV. In this study, we show that,
      following adoptive transfer, virus-specific CD4 and CD8 T cells rapidly
      infiltrate the CNS of MHV-JHM-infected RAG1-/- mice. Adoptive transfer of CD4 T
      cell-enriched donors resulted in more severe clinical disease accompanied by less
      demyelination than was detected in the recipients of undepleted cells. Macrophage
      infiltration into the gray matter of CD4 T cell-enriched recipients was greater
      than that observed in mice receiving undepleted splenocytes. In contrast, CD8 T
      cell-enriched recipients developed delayed disease with extensive demyelination
      of the spinal cord. MHV-JHM-infected RAG1-/- mice receiving donors depleted of
      both CD4 and CD8 T cells did not develop demyelination. These results demonstrate
      that the development of demyelination following MHV infection may be initiated by
      either CD4 or CD8 T cells. Furthermore, they show that CD4 T cells contribute
      more prominently than CD8 T cells to the severity of clinical disease, and that
      this correlates with increased macrophage infiltration into the gray matter.

PMID- 10925318
TI  - Status of activation of circulating vaccine-elicited CD8+ T cells.
AB  - Selective blunting of the status of activation of circulating tumor-specific T
      cells was invoked to explain their paradoxical coexistence with unhampered tumor
      growth. By analogy, lack of tumor regression in the face of observable melanoma
      vaccine-induced T cell responses might be attributed to their status of
      activation. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine
      elicited T cell precursor frequency directly in PBMC of patients with melanoma
      undergoing vaccination with the HLA-A*0201-associated gp100:209-217(210 M)
      epitope (g209-2 M). Furthermore, we tested by intracellular (IC)-FACS analysis
      and quantitative real-time PCR (qRT-PCR) the ability of postvaccination PBMC to
      produce cytokine in response to challenge with vaccine-related epitopes or
      vaccine-matched (HLA-A*0201) melanoma cells. Vaccine-induced enhancement of T
      cell precursor frequency could be detected with tHLA in PBMC from six of eight
      patients studied at frequencies ranging between 0.3 and 2.3% of the total CD8+
      population. Stimulation with vaccine-related epitopes induced IFN-gamma
      expression detectable by IC-FACS or qRT-PCR, respectively, in five and six of
      these patients. Furthermore, down-regulation of tHLA staining was noted upon
      cognate stimulation that could be utilized as an additional marker of T cell
      responsiveness. Finally, we observed in six patients an enhancement of reactivity
      against vaccine-matched tumor targets that was partly independent of documented
      vaccine-specific immune responses. A strong correlation was noted between tHLA
      staining of postvaccination PBMC and IFN-gamma expression by the same samples
      upon vaccine-relevant stimulation and assessed either by IC-FACS or qRT-PCR.
      Thus, blunting of the status of T cell activation on itself cannot easily explain
      the lack of clinical responses observed with vaccination.

PMID- 10925319
TI  - B and T cell responses to the spliceosomal heterogeneous nuclear
      ribonucleoproteins A2 and B1 in normal and lupus mice.
AB  - Autoantibodies directed against spliceosomal heterogeneous nuclear
      ribonucleoproteins (hnRNPs) are a typical feature of rheumatoid arthritis,
      systemic lupus erythematosus, and mixed-connective tissue disease. With the aim
      of investigating a potential pathogenic role of these Abs, we have studied the Ab
      response to A2/B1 hnRNPs in different murine models of lupus. The specificity of
      anti-A2/B1 Abs was tested with a series of 14 overlapping synthetic peptides
      covering the region 1-206 of A2 that contains most of the epitopes recognized by
      patients' Abs. A major epitope recognized very early during the course of the
      disease by Abs from most of MRL lpr/lpr mice but not from other lupus mice and
      from mice of different MHC haplotypes immunized against B1 was identified in
      residues 50-70. This peptide contains a highly conserved sequence RGFGFVTF also
      present in other hnRNPs and small nuclear ribonucleoproteins. Abs reacting with a
      second A2 epitope identified in residues 35-55 were detectable several weeks
      later, suggesting an intramolecular B cell epitope spreading during the course of
      the disease. We identified several T cell epitopes within the region 35-175 that
      generated an effective Th cell response with IL-2 and IFN-gamma secretion in
      nonautoimmune CBA/J mice sharing the same MHC haplotype H-2k as MRL/lpr mice.
      None of the peptides stimulated T cells primed in vivo with B1. Because Abs to
      peptide 50-70 were detected significantly earlier than Abs reacting with other A2
      peptides and the protein itself, it is possible that within the protein, this
      segment contains residues playing an initiator role in the induction of the anti
      A2/B1 and antispliceosome Ab response.

PMID- 10925320
TI  - Development of streptococcal pyrogenic exotoxin C vaccine toxoids that are
      protective in the rabbit model of toxic shock syndrome.
AB  - Streptococcal pyrogenic exotoxin C (SPE C) is a superantigen produced by many
      strains of Streptococcus pyogenes that (along with streptococcal pyrogenic
      exotoxin A) is highly associated with streptococcal toxic shock syndrome (STSS)
      and other invasive streptococcal diseases. Based on the three-dimensional
      structure of SPE C, solvent-exposed residues predicted to be important for
      binding to the TCR or the MHC class II molecule, or important for dimerization,
      were generated. Based on decreased mitogenic activity of various single-site
      mutants, the double-site mutant Y15A/N38D and the triple-site mutant
      Y15A/H35A/N38D were constructed and analyzed for superantigenicity, toxicity
      (lethality), immunogenicity, and the ability to protect against wild-type SPE C
      induced STSS. The Y15A/N38D and Y15A/H35A/N38D mutants were nonmitogenic for
      rabbit splenocytes and human PBMCs and nonlethal in two rabbit models of STSS,
      yet both mutants were highly immunogenic. Animals vaccinated with the Y15A/N38D
      or Y15A/H35A/N38D toxoids were protected from challenge with wild-type SPE C.
      Collectively, these data indicate that the Y15A/N38D and Y15A/H35A/N38D mutants
      may be useful as toxoid vaccine candidates.

PMID- 10925321
TI  - Carotid Doppler high-intensity transient signals in dilated cardiomyopathy.
AB  - BACKGROUND: Thromboembolism is an infrequent but serious complication in dilated
      cardiomyopathy (DCM), and the role of primary preventive antithrombotic or
      anticoagulation therapy is undetermined. High-intensity transient signals (HITS)
      by Doppler ultrasound representing microemboli have been described in various
      clinical settings associated with increased risk of stroke. This study assessed
      the feasibility, reproducibility, and prevalence of HITS in patients with DCM.
      METHODS: Thirty patients with severely reduced left ventricular ejection fraction
      (< or = 35%, mean 25%) and New York Heart Association class II to III who were
      not receiving antithrombotic or anticoagulant therapy and 20 age-matched normal
      subjects were prospectively examined. Patients with atrial fibrillation,
      significant cardiac valvular heart disease, a history of cerebrovascular disease,
      and those who otherwise required antithrombotic or anticoagulation therapy were
      excluded. One-hour pulsed-wave Doppler recordings over the common carotid artery
      (CCA) were performed on 3 separate days in each subject by a single, experienced,
      blinded sonographer with a 4-MHz probe (TC-2000, Nicolet/EME) with a specially
      designed probe holder. Studies were read in a blinded, random fashion by 2
      independent, experienced HITS Doppler recording readers. RESULTS: HITS in the CCA
      were detected in 6 (20%) of 30 patients with DCM and in 3 (15%) of 20 volunteers.
      This difference was not statistically significant. Intrareader and interreader
      reproducibility were high (kappa = 0.91 and 0.84, respectively; P <.001), whereas
      intrasubject reproducibility over the 3 visits was moderate to low (kappa =
      0.22). There was no significant difference between HITS characteristics, that is,
      intensity and duration, in patients versus controls. CONCLUSIONS: The prevalence
      of CCA HITS in patients with clinically stable heart failure who are not
      receiving anticoagulation/antithrombotic therapy and are not in atrial
      fibrillation is low and not significantly different from normal patients. These
      data suggest that HITS monitoring is not a viable surrogate marker for increased
      thromboembolic risk in such patients with DCM.

PMID- 10925328
TI  - Cardiovascular implications of the factor V Leiden mutation.

PMID- 10925329
TI  - Association between week of the month and death from acute myocardial infarction
      in Washington state, 1988 to 1997.
AB  - BACKGROUND: Deaths caused by substance abuse, circulatory disorders, and external
      causes such as suicide, homicide, and accidents are more likely to occur during
      the first week of the month than the last week of the preceding month. The
      purpose of this report is to determine if death caused by acute myocardial
      infarction occurs more often in the first 7 days of the month than in the last 7
      days of the preceding month. METHODS AND RESULTS: This study used computerized
      death records for Washington state from 1988 to 1997. There were 401,314 deaths,
      of which 33,436 (8.3%) had an underlying cause of acute myocardial infarction.
      The week of the month during which death occurred was defined as occurring during
      the first 7 days of the month or the last 7 days of the preceding month. R, the
      ratio of the number of deaths during the first 7 days of the month to the number
      of deaths in the last 7 days of the preceding month multiplied by 100, was
      calculated, as were 95% confidence intervals. R values for other cardiac causes
      and substance abuse-related causes were also calculated. Deaths caused by acute
      myocardial infarction occurred more often in the first week of the month than in
      the last week of the previous month (R = 104.4, 95% confidence interval 101. 7
      107.8). This pattern of death was most apparent for individuals > or =75 years of
      age (R = 107.3, 95% confidence interval 102.1-111.1) and was not evident for
      other cardiac causes, including congestive heart failure or myocardial ischemia.
      By comparison, substance abuse-related deaths occurred much more frequently
      during the first week of the month (R = 117.6, 95% confidence interval 110.0
      125.8). CONCLUSIONS: This pattern of death for acute myocardial infarction may be
      in part caused by stressful events associated with the first week of the month.

PMID- 10925330
TI  - Electrocardiographic presentation of blacks with first myocardial infarction does
      not explain race differences in thrombolysis administration.
AB  - BACKGROUND: Previous studies have suggested that thrombolysis is used less often
      in blacks than in whites. However, whether the greater prevalence of
      contraindications or less specific electrocardiographic manifestations of
      myocardial infarction (MI) account for this difference is unclear. METHODS AND
      RESULTS: We studied 498 consecutive patients (32% blacks) with first MI. Initial
      electrocardiograms were analyzed, blinded to race and outcome, for ST-segment
      deviation and bundle branch block to determine eligibility for thrombolysis. The
      relation of electrocardiographic eligibility for thrombolysis and actual use of
      thrombolysis in both races was explored. Among blacks, 45% received thrombolysis
      compared with 66% of whites (P <.001). A similar proportion of blacks and whites
      were eligible for thrombolysis (59% and 66% respectively, P =. 116), but 62% of
      electrocardiography-eligible blacks were treated with thrombolysis compared with
      75% of whites (P =.016). After accounting for eligibility for electrocardiography
      and other clinical variables likely to affect the decision to administer
      thrombolysis by means of conditional logistic regression, blacks were still less
      likely to receive thrombolysis (relative risk 0.73; 95% confidence interval 0.55
      to 0.97). CONCLUSIONS: We conclude that the differences in thrombolysis
      administration to blacks and whites are not accounted for by differences in
      electrocardiographic presentation or other measured variables. Unmeasured
      differences in clinical presentation of MI may explain racial differences in
      thrombolysis and merits further study.

PMID- 10925331
TI  - Thrombocytopenia complicating treatment with intravenous glycoprotein IIb/IIIa
      receptor inhibitors: a pooled analysis.
AB  - BACKGROUND: Despite the increasingly prevalent role of platelet glycoprotein (GP)
      IIb/IIIa receptor inhibitors in acute coronary syndromes and percutaneous
      coronary interventions, the incidence and clinical relevance of thrombocytopenia
      occurring with their use remain unclear. METHODS: We identified 8 placebo
      controlled, randomized, large trials of GP IIb/IIIa receptor inhibitors reporting
      the incidence of thrombocytopenia, grouped by severity. The clinical courses of
      42 patients with GP IIb/IIIa-related thrombocytopenia in these studies and other
      case reports were reviewed for bleeding complications. RESULTS: Abciximab
      increased mild thrombocytopenia compared with placebo (4.2% vs 2.0%; P <.001;
      odds ratio 2.14) and increased severe thrombocytopenia compared with placebo
      (1.0% vs 0.4%; P =.01; odds ratio 2.48). Small-molecule IIb/IIIa inhibitors did
      not significantly increase mild or severe thrombocytopenia compared with placebo.
      Mild thrombocytopenia occurred more frequently in acute coronary syndrome trials
      than in coronary intervention trials, even in patients not receiving any IIb/IIIa
      inhibitors. No major bleeding sequelae were reported in 23 patients with severe
      thrombocytopenia or in 19 patients with profound thrombocytopenia. CONCLUSIONS:
      Abciximab, but not eptifibatide or tirofiban, increases the incidence of
      thrombocytopenia compared with placebo in patients also treated with heparin.
      Thrombocytopenia associated with GP IIb/IIIa inhibition does not routinely lead
      to severe bleeding complications.

PMID- 10925332
TI  - Low intracellular magnesium levels promote platelet-dependent thrombosis in
      patients with coronary artery disease.
AB  - BACKGROUND: Although reduced intracellular levels of magnesium have been
      described in patients with acute myocardial infarction, its significance as a
      regulator of thrombosis remains unknown. METHODS AND RESULTS: To determine
      whether reduced intracellular levels of magnesium enhance platelet-dependent
      thrombosis, we evaluated 42 patients with coronary artery disease (CAD) by
      exposing porcine aortic media to their flowing unanticoagulated venous blood for
      5 minutes by using an ex vivo perfusion (Badimon) chamber. Baseline analysis
      demonstrated significant associations between intracellular levels of magnesium,
      platelet-dependent thrombosis (P =.02), and platelet P-selectin (CD62P)
      expression (P <.05). Patients were divided into 2 groups: below (n = 22) and
      above (n = 20) the median intracellular levels of magnesium (1.12 microg/mg
      protein). There were no significant differences in age, body mass index, serum
      lipids, fibrinogen, platelet count, or serum magnesium levels between the two
      groups. Platelet-dependent thrombosis was significantly higher in patients with
      intracellular levels of magnesium below compared with above median (150 +/- 128
      vs 45 +/- 28 microm(2)/mm, P <.004). Neither platelet aggregation nor CD62P
      expression was significantly different between the two groups. CONCLUSIONS:
      Platelet-dependent thrombosis was significantly increased in patients with stable
      CAD with low intracellular levels of magnesium, suggesting a potential role for
      magnesium supplementation in CAD.

PMID- 10925333
TI  - Underutilization of oral anticoagulant therapy for stroke prevention in elderly
      patients with heart failure.
AB  - BACKGROUND: Oral anticoagulant therapy is the most effective prophylaxis against
      stroke in atrial fibrillation. Relatively few studies have examined the use of
      oral anticoagulant therapy for stroke prevention in a large cohort of elderly
      patients with heart failure. To examine the use of stroke prevention therapy, we
      studied elderly patients with heart failure admitted to 30 hospitals in northeast
      Ohio between 1992 and 1994. METHODS AND RESULTS: The sample consisted of 12,911
      Medicare-insured patients > or =65 years of age who were consecutively admitted
      with a principal diagnosis of heart failure between 1992 and 1994. Baseline
      demographic and clinical characteristics for patients with the diagnosis of
      atrial fibrillation were calculated. Bivariate associations between receiving
      anticoagulant therapy and select demographic and clinical variables were
      calculated. In our cohort of patients with heart failure, 2093 had atrial
      fibrillation (16%). Only 414 (20%) of the patients with atrial fibrillation
      received oral anticoagulant therapy. Older age and history of gastrointestinal
      bleeding were significantly negatively associated with receiving oral
      anticoagulant therapy. History of stroke or transient ischemic attack was
      positively associated with receiving oral anticoagulant therapy. CONCLUSIONS:
      Atrial fibrillation is common in older patients with heart failure; oral
      anticoagulant therapy for stroke prevention, which has been shown to be
      effective, is underutilized in this patient population.

PMID- 10925334
TI  - Strict reliance on a computer algorithm or measurable ST segment criteria may
      lead to errors in thrombolytic therapy eligibility.
AB  - BACKGROUND: There is accumulating evidence that thrombolytic therapy is underused
      among eligible patients with acute myocardial infarction. We sought to determine
      whether potential errors in electrocardiographic diagnosis might be a
      contributing factor. METHODS: Seventy-five electrocardiograms were interpreted on
      2 separate occasions by 3 cardiologists. Two criteria were compared for
      thrombolysis eligibility: (1) measurement of > or =1 mm ST-segment elevation in 2
      contiguous leads (measured) and (2) criterion 1 plus the subjective opinion that
      the changes represented acute transmural injury (interpretive). The results were
      compared with computerized interpretations by the Marquette 12SL system. RESULTS:
      Raw agreement and agreement corrected for chance between raters for both criteria
      were excellent and tended to be better for interpretive compared with measured
      criteria (kappa = 0.89 vs 0.78, respectively). Strict reliance on measured
      electrocardiographic criteria alone would have resulted in overuse of
      thrombolysis among all 3 raters. Based on the consensus opinion, the absolute
      overuse of thrombolysis would have been approximately 15% (P <.0034). The
      computer algorithm had a specificity of 100% and a sensitivity of 61.5%. Reliance
      on the computerized interpretation alone would have lead to underuse of
      thrombolytic therapy compared with consensus opinion (21.3% vs 34. 6%; P <.005).
      CONCLUSION: Agreement for suspected acute myocardial infarction tended to be
      better when the appearance of the ST segments was added to measurable ST
      elevation criteria. Strict reliance on measurable criteria may lead to the
      inappropriate overuse of thrombolysis. Although the Marquette 12SL system has
      excellent specificity, it has poor sensitivity for the diagnosis of thrombolysis
      eligible AMI. Reliance on computerized electrocardiographic interpretation would
      lead to the inappropriate underuse of thrombolytic therapy in situations in which
      qualifying electrocardiographic criteria are actually met.

PMID- 10925335
TI  - Balloon angioplasty in infants with aortic obstruction after the modified stage I
      Norwood procedure.
AB  - BACKGROUND: The incidence of coarctation after stage I Norwood procedure varies
      between 11% and 37%, and it contributes to late death after this operation. We
      describe the incidence and report the results of percutaneous balloon angioplasty
      of neoaortic arch obstruction in patients after the modified Norwood procedure
      for hypoplastic left heart syndrome (HLHS). METHODS: During a period of 5 years,
      136 patients (94 male, 42 female) underwent a first stage modified Norwood
      procedure for HLHS. All 95 survivors (69.8%) underwent cardiac catheterization
      before the second stage. Neoaortic arch obstruction was diagnosed on
      documentation of a peak systolic gradient of >10 mm Hg across the arch associated
      with angiographic evidence of localized narrowing of the aortic lumen. RESULTS:
      Twenty-one (22.1%) of the 95 survivors were documented to have neoaortic arch
      obstruction. Seventeen patients underwent percutaneous balloon angioplasty for
      the relief of the neoaortic arch obstruction. The predilatation peak gradient
      across the arch was reduced significantly by angioplasty from 28.6 +/- 16.9 mm Hg
      (range 10 to 73 mm Hg) to 5.3 +/- 5.2 mm Hg (range 0 to 19 mm Hg) (P <.001). A
      final gradient <10 mm Hg or <70% of the starting gradient was considered a
      success. CONCLUSION: The absence of serious sequelae after the procedure or need
      for reintervention, as shown by our study, makes balloon angioplasty an effective
      technique and the treatment of choice for the relief of recoarctation of the
      neoaortic arch in patients with staged palliation of HLHS.

PMID- 10925336
TI  - Current perspectives on the management of hypertriglyceridemia.
AB  - BACKGROUND: Observational studies have demonstrated that triglycerides are an
      independent risk factor for coronary heart disease. Atherothrombosis may be
      mediated by uptake and incorporation of triglyceride-rich lipoproteins by
      macrophages and through an association with small, dense LDL and HDL particles.
      There are considerable data that lowering LDL cholesterol reduces cardiovascular
      events. However, the importance of triglyceride lowering remains elusive.
      METHODS: A summary of major arteriographic and clinical end point trials is
      reviewed. Studies evaluating various strategies, including dietary and hygienic
      measures as well as pharmacologic therapies, are discussed. RESULTS: Dietary
      reduction of saturated fat, coupled with aerobic activity, reduces triglyceride
      levels approximately 20% to 24%. Omega-3 fatty acids may also reduce triglyceride
      levels appreciably. Effective pharmacologic therapies that lower triglyceride
      levels include nicotinic acid (20% to 40%), fibrates (20% to 55%), and statins
      (10% to 30%). Nevertheless, an independent benefit of triglyceride lowering on
      coronary event rate has not been demonstrated. CONCLUSIONS: There are little data
      that triglyceride reduction improves cardiovascular event rate. In contrast,
      lowering LDL cholesterol and, more recently, raising HDL cholesterol are proven
      therapies in coronary heart disease prevention. As such, these modalities remain
      the top priority in the management of dyslipidemia with triglyceride reduction as
      an adjunctive consideration.

PMID- 10925337
TI  - Long-distance air travel soon after an acute coronary syndrome: a prospective
      evaluation of a triage protocol.
AB  - BACKGROUND: An increasing number of patients have an acute coronary syndrome
      while abroad. Such an event may entail significant emotional and financial
      stress, and patients are usually anxious to return home as soon as possible. The
      safety of long-distance air travel soon after an acute coronary syndrome is,
      however, uncertain, and few data exist regarding the evaluation of such patients,
      the proper timing and conditions of the flight, and short-term complications.
      METHODS AND RESULTS: We prospectively evaluated 21 tourists who had an acute
      coronary syndrome in Jerusalem. Patients at high risk were offered angiography;
      others underwent stress testing. Telephone interviews were conducted a few weeks
      after the patients returned home, and follow-up information was obtained.
      Patients flew home 18.2 +/- 11 days (mean +/- SD) after the acute event. Flight
      duration was substantial (12.5 +/- 3 hours). No patient had cardiac symptoms en
      route. At follow-up (21.3 +/- 13 days), all but 2 patients were alive and free of
      cardiac symptoms. CONCLUSIONS: A long-distance flight within 2 to 3 weeks after
      an acute coronary syndrome is reasonably safe, provided significant ischemia is
      excluded or treated.

PMID- 10925338
TI  - Increased plasma level of soluble E-selectin in acute myocardial infarction.
AB  - BACKGROUND: E-selectin, also known as endothelial cell leukocyte adhesion
      molecule-1, is a member of the selectin family of adhesion molecules and is
      expressed on vascular endothelial cells in inflammatory reactions. The induction
      of surface E-selectin expression by endothelial cells is considered a marker of
      activation. METHODS AND RESULTS: We examined the plasma soluble E-selectin (sE
      selectin) level in 41 patients within 6 hours after the onset of acute myocardial
      infarction (AMI) and in 37 patients with stable exertional angina and 27 control
      patients. Blood samples were obtained on admission, after reperfusion therapy,
      and at 4 hours, 8 hours, 12 hours, 24 hours, 48 hours, 3 days, 5 days, 1 week,
      and 2 weeks after admission in the AMI group. In this group, 21 patients had a
      history of prodromal unstable angina before infarction and 20 had sudden onset of
      infarction. The plasma sE-selectin level (ng/mL) on admission was higher in the
      AMI group than in the stable exertional angina group and control group (38.5 +/-
      3.1 vs 28.5 +/- 1.5, P <.01, 26.0 +/- 1.8, P <.01, respectively). In addition,
      plasma sE-selectin levels were higher in the patients with AMI with prodromal
      unstable angina than in those with a sudden onset of infarction on admission
      (44.7 +/- 5.4 vs 32.0 +/- 2.1, P <.05). The plasma sE-selectin level decreased
      slowly during the chronic phase both in patients with AMI with prodromal unstable
      angina (from 44.7 +/- 5.4 to 33.8 +/- 3.4, P <.01) and those with a sudden onset
      of infarction (from 32.0 +/- 2.1 to 24.9 +/- 2.4, P <.01). CONCLUSIONS: These
      results suggest that an increase of sE-selectin may reflect enhanced endothelial
      cell activation in patients with AMI. The higher sE-selectin level in patients
      with AMI with prodromal unstable angina may have been associated with repeated
      episodes of myocardial ischemia and reperfusion.

PMID- 10925339
TI  - Effect of atorvastatin on blood lipid levels in the first 2 weeks of treatment: a
      randomized, placebo-controlled study.
AB  - BACKGROUND: The rate and degree of LDL cholesterol reduction, in the first 2
      weeks of therapy, may relate to the early benefit of hydroxymethyl glutaryl
      coenzyme A reductase inhibitor therapy. In patients with similar baseline LDL
      cholesterol levels as in the Cholesterol and Recurrent Events (CARE) trial, we
      report the results of a 2-week placebo-controlled, double-blind investigation of
      10 mg/day atorvastatin. METHODS AND RESULTS: The 22 participants were non
      Hispanic whites younger than age 72 (average age 47 years) who were modestly
      overweight and had normal blood pressure. There were no significant baseline
      lipid and lipoprotein differences. By day 5, there were significant (P <.01)
      reductions in total cholesterol and LDL levels. The total cholesterol level fell
      by 25% (226 mg/dL to 169 mg/dL) and LDL cholesterol fell 35% by day 14 (P <.001).
      Triglyceride levels declined by 24% (from 137 mg/dL to 104 mg/dL) by day 14, but
      this was not statistically significant. There was no significant difference in
      HDL cholesterol. The total/HDL level dropped from 4.54 (day 0) to 3.32 (day 14),
      and the LDL/HDL level dropped from 2.92 to 1.88; both results were highly
      significant (P <. 001). CONCLUSION: The rapid lipid reduction observed with
      atorvastatin may benefit the vascular endothelium.

PMID- 10925340
TI  - Epidemiologic study of use of resources in patients with unstable angina: the
      EARISA registry. On behalf on the EARISA Investigators (Epidemiologia
      dell'Assorbimento di Risorse nell'Ischemia, Scompenso e Angina).
AB  - AIM: The EARISA Registry was designed to describe diagnostic and therapeutic
      resources used in Italian cardiology centers for patients with the
      epidemiologically most relevant cardiac diseases. This article focuses on
      patients with unstable angina; characteristics associated with invasive
      procedures were specifically analyzed. METHODS AND RESULTS: Information was
      collected over a 2-week period on 1420 patients with unstable angina discharged
      from 308 cardiology centers. The mean length of stay was 9 +/- 6 days; 51% of
      patients were admitted to a coronary care unit (mean length of stay, 4 +/- 3
      days). Noninvasive procedures included echocardiography (64%), Holter monitoring
      (25%), exercise stress testing (24%), and echocardiographic stress testing or
      nuclear imaging (7%). Invasive procedures were coronary angiography (39%) and
      percutaneous transluminal coronary angioplasty or coronary artery bypass grafting
      (13%). Unstable angina had a greater impact on invasive procedures than acute
      myocardial infarction. Variables independently associated with a higher rate of
      coronary angiographic procedures were younger age, higher technologic level of
      the hospital, and need for intravenous therapy. CONCLUSION: In Italy,
      approximately half the patients with unstable angina are admitted to hospitals
      without catheterization laboratories or cardiac surgery facilities. This fact
      supports the concept that treatments that can be administered in all types of
      hospitals are more likely to affect the outcome of patients with unstable angina.
      Overall, the rates of coronary angiography and revascularization procedures
      appeared low, and the setting where cardiologists practice, rather than patient
      characteristics, is the major determinant of the care given to patients with
      unstable angina.

PMID- 10925341
TI  - A randomized comparison of elective high-pressure stenting with balloon
      angioplasty: six-month angiographic and two-year clinical follow-up. On behalf of
      AS (Angioplasty or Stent) trial investigators.
AB  - BACKGROUND: Previous randomized trials have shown beneficial effects of coronary
      stenting on restenosis and event-free survival rates. However, it has not yet
      been fully established if routine high-pressure stenting with an antiplatelet
      regimen can show similar results. METHODS: We compared the 6-month angiographic
      restenosis rate and 2-year event-free survival rate in 400 patients randomly
      assigned to stent or angioplasty. Aspirin and ticlopidine were prescribed in both
      groups. RESULTS: The procedural success rate did not significantly differ between
      the stent and angioplasty groups (97.92% vs 97.45%, P = not significant). No
      stent thrombosis was found. The 6-month restenosis rate was lower in the stent
      group (18. 18% vs 24.87%, P =.055). At 2 years target lesion revascularization
      rate was 17.19% in the stent group and 25.51% in the angioplasty group (P =.02,
      33% reduction). No significant differences with regard to death and myocardial
      infarction were observed. Event-free survival rate at 6, 12, and 24 months was
      86.77% vs 78.84%, 84.13% vs 76.70%, and 83.07% vs 73.54% for stent and
      angioplasty groups, respectively (P =.0172). CONCLUSIONS: The 6-month
      angiographic and 2-year clinical outcomes were better in patients who received
      stent than in those after balloon angioplasty. The difference in 2-year event
      free survival rate was explained by a reduction in target lesion
      revascularization rate in the stent group.

PMID- 10925342
TI  - Homocysteine, lipoprotein(a), and restenosis after percutaneous transluminal
      coronary angioplasty: a prospective study.
AB  - BACKGROUND: Restenosis complicates 30% to 40% of angioplasty procedures and may
      be unrelated to traditional coronary risk factors. Homocysteine, lipoprotein(a),
      and methylenetetrahydrofolate reductase (MTHFR 677T) (a genetic determinant of
      plasma homocysteine concentrations) are novel risk factors for coronary artery
      disease. Their roles in restenosis are unclear, and the potential synergism
      between homocysteine and lipoprotein(a) has not previously been studied. The
      objective of this study was to determine the relations among homocysteine,
      lipoprotein (a), MTHFR 677T, and restenosis after percutaneous transluminal
      coronary angioplasty. METHODS: This prospective study enrolled patients with
      successful elective percutaneous transluminal coronary angioplasty or stenting of
      a single, de novo, native coronary lesion. Fasting blood was drawn the morning of
      the procedure for homocysteine, lipoprotein(a), and MTHFR 677T. Follow-up
      angiography was performed 6 months after the procedure or earlier if clinically
      indicated. All cineangiograms were analyzed quantitatively. RESULTS: A total of
      144 (92%) of 156 eligible patients underwent follow-up coronary angiography. The
      overall angiographic restenosis rate (residual stenosis >50%) was 31%. Mean
      homocysteine concentration was 10.1 +/- 3.7 micromol/L. Plasma homocysteine
      concentrations were not significantly different in patients with or without
      angiographic restenosis (9.6 +/- 3.3 vs 10.3 +/- 3.8 micromol/L; P =.31). Mean
      lipoprotein(a) concentration was 21.2 +/- 20.1 mg/dL. Plasma lipoprotein(a)
      concentrations were not significantly different in patients with or without
      restenosis (21.9 +/- 21.8 vs 20.9 +/- 19.5 mg/dL). Homozygosity for MTHFR 677T
      was present in 6.5% and was not associated with increased restenosis. No
      interaction between homocysteine and lipoprotein(a) was detected. CONCLUSIONS:
      Homocysteine, lipoprotein(a), and MTHFR 677T are not associated with restenosis
      after percutaneous transluminal coronary angioplasty.

PMID- 10925343
TI  - Cardiac tamponade in the "new device" era: evaluation of 6999 consecutive
      percutaneous coronary interventions.
AB  - BACKGROUND: The incidence of cardiac perforation and pericardial tamponade
      appears to be increasing in the era of new coronary interventional devices
      compared with coronary balloon angioplasty. METHODS AND RESULTS: We reviewed 6999
      consecutive percutaneous coronary interventions performed during 1994 to 1996 in
      a single urban university hospital catheterization laboratory. Data had been
      collected prospectively as part of an ongoing quality assurance program. Fifteen
      patients had cardiac tamponade within 36 hours of the procedure. Only 6 of these
      occurred during the interventional procedure; the others occurred 2 to 36 hours
      later. The median patient age was 72 years. Nine (60%) patients were female.
      Three patients received abciximab. Five perforations were at the target coronary
      artery site, 3 were caused by a guide wire tip in the distal part of the target
      artery, and 7 represented right ventricular perforations caused by a temporary
      pacemaker wire. Five of the 7 right ventricular perforations occurred during
      rotational atherectomy procedures. Diagnosis was aided by immediate
      echocardiography. Treatment was medical, including pericardiocentesis, in 6
      cases. The other 9 patients required surgical drainage and repair. All patients
      survived the index hospitalization. At 18-month follow-up, 1 patient had died,
      and all others were without apparent sequelae. CONCLUSIONS: Tamponade after
      percutaneous coronary intervention is not rare in the "new device" era (overall
      incidence 0.2%); tamponade after percutaneous coronary intervention is often
      delayed and may occur outside the catheterization suite; patients are more likely
      to be female and elderly; immediate echocardiography is an essential aid to
      diagnosis and prompt treatment; and the use of temporary right ventricular pacing
      catheters must be reexamined.

PMID- 10925344
TI  - Echocardiographic determinants of left ventricular ejection fraction after acute
      myocardial infarction.
AB  - OBJECTIVE: This study was performed to determine if factors other than the size
      of regional dysfunction influence the global left ventricular ejection fraction
      after acute myocardial infarction. BACKGROUND: Left ventricular ejection fraction
      is an important prognostic variable after acute myocardial infarction. Although
      infarct size is known to affect the subsequent global left ventricular ejection
      fraction, it remains unclear whether other factors such as site or severity of
      the wall motion abnormality influence the ejection fraction after acute
      myocardial infarction. METHODS: Sixty-nine consecutive patients (mean age 61 +/-
      14 years, 46 [67%] male) who did not receive thrombolytic therapy or undergo
      early revascularization were studied by echocardiography 1 week after Q-wave
      myocardial infarction. The absolute size of the region of abnormal wall motion
      (AWM) and the percentage of the endocardium involved (%AWM) were quantitated
      along with the wall motion score. A severity index was then derived as the mean
      wall motion score within the region of AWM. Site of myocardial infarction was
      classified as either anterior or inferior from the endocardial map. Left
      ventricular ejection fraction was measured by Simpson's method with 2 apical
      views. RESULTS: Twenty-nine (42%) patients had anterior and 40 had inferior
      myocardial infarction. The mean left ventricular ejection fraction was
      significantly lower in anterior than in inferior myocardial infarction (44.8% +/-
      11.5% vs 53% +/- 8.6%; P =. 001). The mean %AWM was greater in anterior than in
      inferior myocardial infarction (32.1 +/- 15.5 vs 22.4 +/- 14.1; P =.01). The mean
      wall motion score was greater in anterior than in inferior myocardial infarction
      (9.8 +/- 6.4 vs 6.4 +/- 4.4; P =.01). The mean severity index did not differ by
      site. Multiple regression analysis demonstrated that, in descending order of
      importance, %AWM, extent of apical involvement, and site of myocardial infarction
      were independent determinants of global left ventricular ejection fraction.
      CONCLUSIONS: For myocardial infarctions of similar size, left ventricular
      ejection fraction is lower when apical involvement is extensive and the site of
      infarction is anterior. This site-dependent difference may be related to
      characteristics specific to the apex.

PMID- 10925345
TI  - Contrast echocardiography is superior to tissue harmonics for assessment of left
      ventricular function in mechanically ventilated patients.
AB  - BACKGROUND: Assessment of left ventricular function by echocardiography is
      frequently challenging in mechanically ventilated patients. We evaluated the
      potential value of contrast-enhanced imaging and tissue harmonic imaging over
      standard fundamental imaging for endocardial border detection (EBD) in these
      patients. METHODS AND RESULTS: Fifty patients underwent standard transthoracic 2D
      echocardiography and were imaged in fundamental and tissue harmonic modes and
      subsequently with intravenous contrast (Optison). Two echocardiographers reviewed
      all studies for ease of visualization of endocardial border segments and scoring
      of wall motion. EBD for each wall segment was graded from 1 to 4 (1 = excellent
      EBD). Wall motion was scored by a standard 16-segment model and 1 to 5 scale.
      Studies were categorized as nondiagnostic if 4 of 6 segments in the apical 4
      chamber view were either poorly seen or not seen (EBD score 3 or 4).
      Quantification of ejection fraction was independently performed offline.
      Visualization of 68% of all segments improved with contrast echocardiography
      versus 17% improvement with tissue harmonics compared with fundamental mode.
      Significant improvement (poor/not seen to good/excellent) occurred in 60% of
      segments with contrast echocardiography versus 18% with tissue harmonics. A total
      of 850 segments were deemed poor/not seen, 78% of which improved to
      good/excellent with contrast echocardiography versus 23% with tissue harmonics.
      Interobserver agreement on EBD was 64% to 70%. Conversion of nondiagnostic to
      diagnostic studies occurred in 85% of patients with contrast echocardiography
      versus 15% of patients with tissue harmonics. Scoring of wall motion with
      fundamental mode, tissue harmonics, and contrast echocardiography was possible in
      61%, 74%, and 95% of individual segments, respectively (P <.001). Wall motion
      scoring was altered in 17% of segments with contrast echocardiography and in 8%
      with tissue harmonics. Interobserver agreement on wall motion scoring was 84% to
      88%. Contrast echocardiography permitted measurement of ejection fraction 45% (P
      =.003) more often over fundamental mode versus a 27% (P =.09) increase with
      tissue harmonics. CONCLUSIONS: Contrast echocardiography is superior to tissue
      harmonic imaging for EBD, wall motion scoring, and quantification of ejection
      fraction in mechanically ventilated patients.

PMID- 10925346
TI  - Dilation and reduced distensibility of carotid artery in patients with abdominal
      aortic aneurysms.
AB  - BACKGROUND: Although patients with abdominal aortic aneurysms (AAA) frequently
      have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is
      the opposite of the occlusion characteristic of atherosclerotic disease. It has
      been suggested that this dilatative disease is caused by an alteration in
      connective tissue metabolism in systemic arterial wall. Such a condition might
      alter systemic arterial diameter and wall behavior. We investigated arterial
      characteristics in AAA patients, including morphologic changes and wall mechanics
      in the carotid artery. METHODS AND RESULTS: Atherosclerotic intimal changes such
      as intima-media thickness (IMT), plaque formation, diameter, and wall elasticity
      of the carotid artery were determined ultrasonographically in patients with AAA
      (n = 102) and compared with age-matched patients with the atherosclerotic
      diseases arteriosclerosis obliterans (ASO, n = 115) and coronary artery disease
      (CAD, n = 123) and with age-matched healthy control patients (CTL, n = 45).
      Intimal disease in AAA was significantly milder than in ASO, at the same level as
      CAD, and more severe than in CTL. Although end-diastolic luminal diameters (mm)
      in AAA (7.05 +/- 1.08), ASO (6.74 +/- 0.18), and CAD (6.66 +/- 0.83) were
      significantly higher than in CTL (5.97 +/- 0.93), they were also excessively
      increased compared with the equivalent diameters seen in ASO (P <.01) and CAD (P
      <.01). Luminal distensibility (x 10(-6) cm(2). dyne(-1)) in AAA (0.83 +/- 0.48)
      was excessively decreased compared not only with CTL (1.70 +/- 1.11, P <.01) but
      also with ASO (1.12 +/- 0.47, P <.01) and CAD (1.18 +/- 0.59, P <. 01). These
      relations remained true when adjusted for blood pressure and luminal diameter.
      Intra-AAA group analysis showed that distensibility in ruptured cases (n = 14)
      was significantly lower than in nonruptured cases (n = 88) (0.58 +/- 0.24 vs 0.88
      +/- 0.50, P <.05). CONCLUSIONS: Excessive arterial dilation and reduced
      distensibility without severe intimal disease were found in the carotid arteries
      of patients with AAA. This suggests that these patients may be subject to
      systemic arterial alterations, including structural and functional abnormalities.

PMID- 10925347
TI  - Structural and compliant anatomy of the patent foramen ovale in patients
      undergoing transcatheter closure.
AB  - BACKGROUND: Most current intracardiac closure devices target the atrial septal
      defect. However, defects such as the patent foramen ovale (PFO) have unique
      structural features that may influence rational device design. With mounting
      interest in transcatheter techniques for closure of PFO in patients with
      cryptogenic stroke, a clearer understanding of these features is warranted.
      METHODS: Retrospectively, we reviewed angiograms obtained at the time of
      transcatheter closure of PFOs with a non-self-centering device in a group of 21
      patients with a history of stroke. RESULTS: The PFO appeared as a tunnel of
      varying length (2.4 to 19.5 mm, mean 9.1 +/- 4.7 mm) bounded by septum secundum
      and septum primum. The potential area of the defect was as small as 12.2 mm(2)
      and as large as 121.1 mm(2). With device placement, the tunnel length shortened
      or disappeared (0.5 +/- 1.6 mm) by inferior displacement of the more compliant
      septum primum. CONCLUSIONS: In patients with PFO referred for transcatheter
      closure, the defect most commonly appeared as a tunnel-like defect between a
      thicker, less compliant septum secundum and a thinner, more compliant septum
      primum. Although the length of the undisturbed tunnel varied widely, the tunnel
      was shortened or eliminated by placement of a non-self-centering device. The
      observation that PFO anatomy can be predictably altered by some devices may have
      an impact on device design or implantation technique.

PMID- 10925348
TI  - Effect of sex, hemodynamics, body size, and other clinical variables on the
      corrected thrombolysis in myocardial infarction frame count used as an assessment
      of coronary blood flow.
AB  - BACKGROUND: Compared with the conventional Thrombolysis In Myocardial Infarction
      (TIMI) flow grade system, the corrected TIMI frame count (CTFC) quantifies
      coronary blood flow in a more reproducible fashion. The purpose of this study was
      to determine if the CTFC is affected by sex, body size, hemodynamics, or other
      selected clinical variables. METHODS AND RESULTS: CTFC was measured in 534
      coronary arteries from 200 consecutive patients referred for coronary
      angiography. CTFC in each artery was related to patient variables (sex, age,
      race, and body surface area), clinical variables (cardiac rhythm, medication use,
      diabetes, hypertension, hypercholesterolemia, smoking, and left ventricular
      hypertrophy), angiographic variables (wall motion abnormality in each coronary
      artery distribution, left ventricular ejection fraction, percent stenosis in the
      artery, and presence of collaterals), and hemodynamic variables (aortic systolic
      and diastolic blood pressure and left ventricular end-diastolic pressure). By
      multivariate analysis, CTFC in all arteries was significantly associated with
      aortic systolic and diastolic pressures and body surface area. In addition, there
      were significant associations between CTFC and age and sex in some but not all
      arteries. Although significant, the absolute change in CTFC associated with these
      variables was small. CONCLUSIONS: CTFC provides a quantitative assessment of
      coronary blood flow that varies only a small amount in association with body
      size, systemic arterial pressure, age, and sex.

PMID- 10925349
TI  - Lack of clinically significant cardiac dysfunction during intermediate dobutamine
      doses in long-term childhood cancer survivors exposed to anthracyclines.
AB  - BACKGROUND: Long-term survivors of childhood cancer treated with anthracyclines
      may have subclinical cardiac dysfunction undetectable at a baseline evaluation.
      Dobutamine stress echocardiography has been proposed as a more sensitive
      screening test, but results of previous studies were influenced by selection
      criteria, infusion protocols, and side effects. METHODS: We applied a modified
      dobutamine stress test (from 5 to 10 to 15 microg/kg, infused over a 5-minute
      period) and evaluated the influence on stress test results of reported risk
      factors for late cardiac toxicity (female sex, younger age at treatment, higher
      dose of anthracycline, and longer duration of follow-up). Seventy-one patients
      (46 male, mean age 15 +/- 5 years) treated with anthracyclines (median dose 240
      mg/m(2)) 1 to 16.5 years before and 20 controls (patients' siblings: 12 male,
      mean age 19 +/- 4 years) were studied. RESULTS: No major side effects were
      recorded. One patient was unable to perform the test because of anxiety. Limiting
      side effects were infrequent (3%) and occurred at a dobutamine dose of > or =10
      microg/kg, when significant changes of hemodynamic and echocardiographic
      parameters were detectable in all cases. Rest systolic and mean blood pressure
      and left ventricular fractional shortening were significantly lower in patients
      than in controls (P <.05), but no differences were found in any of the other
      indexes of cardiac function between the 2 groups at rest and during each
      dobutamine infusion step. A similar increase of global left ventricular function
      (percent of fractional shortening +45% vs +32%) and a decrease of end-systolic
      stress (-33% vs -29%) were documented. Left ventricular relaxation, early
      filling, and both relaxation and compliance improved. In all but one patient with
      reduced global left ventricular function at baseline, time-dependent patterns of
      hemodynamic and echocardiographic responses to dobutamine were similar.
      Previously described risk factors for cardiac toxicity did not influence the time
      changes of the echocardiographic parameters in response to dobutamine.
      CONCLUSIONS: Compared with controls, most of our asymptomatic childhood cancer
      survivors, studied an average of 7 years after treatment with anthracyclines,
      showed normal baseline cardiac function. Our stress test was feasible and safe.
      Compared with modalities used in other studies, shorter infusion periods with
      higher dobutamine doses allowed a higher stress intensity to be reached without
      reducing patient compliance. At dobutamine stress test the response was
      comparable in patients and controls except for one patient. Previously reported
      risk factors for cardiac toxicity had no significant influence on stress test
      results.

PMID- 10925350
TI  - Prognostic value of C-reactive protein levels within six hours after the onset of
      acute myocardial infarction.
AB  - BACKGROUND: Inflammation is an important feature of atherosclerotic lesions, and
      the vulnerability of coronary lesions in acute myocardial infarction (AMI) at the
      time of onset may be related to blood levels of C-reactive protein (CRP) on
      admission, before CRP levels are affected by myocardial damage. METHODS: A total
      of 234 patients with AMI in whom plasma CRP was measured within 6 hours after
      onset were studied. They were divided into 2 groups: group 1 (n = 49) with
      elevated CRP (>/=0.3 mg/dL) on admission within 6 hours after onset and group 2
      (n = 185) with normal CRP (<0.3 mg/dL) within 6 hours after onset. All were
      treated by primary percutaneous transluminal coronary angioplasty with
      provisional stenting. RESULTS: There were no significant differences in baseline
      characteristics between the 2 groups. In-hospital adverse coronary events,
      including coronary reocclusion, reinfarction, target vessel revascularization,
      and death, were significantly more frequent in group 1 (22.4%) than in group 2
      (4.3%, P <.005), and bailout stenting was performed significantly more frequently
      in group 1 (61. 2%) than in group 2 (37.8%, P <.005). In contrast, there were no
      significant differences between the 2 groups in parameters that represent
      myocardial damage, including peak creatine kinase and left ventricular ejection
      fraction. CONCLUSION: CRP levels within 6 hours after the onset of AMI reflect
      the vulnerability of culprit coronary lesions and predict adverse coronary events
      after primary PTCA/stenting.

PMID- 10925351
TI  - Different beta-adrenergic regulation of myocardial contraction and relaxation
      between apical and nonobstructive hypertrophic cardiomyopathy.
AB  - BACKGROUND: The impaired adrenergic control of both inotropic and lusitropic
      reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM)
      but not in those with apical HCM (APH). OBJECTIVES: We examined the influence of
      increases in heart rate and adrenergic stimulation on inotropic and lusitropic
      reserves in HCM and APH with normal resting left ventricular (LV) systolic
      function. METHODS: We evaluated LV isovolumic contraction and relaxation during
      atrial pacing and during supine leg exercise in 7 patients with APH and in 8
      patients with HCM. RESULTS: Heart rate was significantly correlated with LV
      isovolumic contraction and relaxation during pacing and exercise in all patients.
      In all patients with APH, the increase in LV isovolumic contraction was greater
      during exercise (101%) than pacing alone (27%) for similar increase in heart
      rate. In 5 patients with HCM, the increase in LV isovolumic contraction was
      greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with
      HCM the increase in LV isovolumic contraction was similar between during exercise
      (25%) and during pacing alone (22%). In all patients with APH, relaxation was
      shorter during exercise (39%) than pacing alone (16%). Conversely, in patients
      with HCM relaxation was similarly shortened between during pacing alone (20%) and
      during exercise (19%). CONCLUSIONS: The force-frequency and the relaxation
      frequency relations were well-preserved in all patients. In patients with HCM,
      the adrenergic enhancement of force-frequency relation and/or relaxation
      frequency relation was impaired. In patients with APH, however, adrenergic
      control of both force-frequency and relaxation-frequency relations was well
      preserved, which may indicate a preserved beta-adrenergic signaling pathway.

PMID- 10925352
TI  - Left ventricular diastolic filling pattern predicts cardiopulmonary determinants
      of functional capacity in patients with congestive heart failure.
AB  - BACKGROUND: Abnormalities of diastolic function are an important determinant of
      exercise intolerance in patients with heart failure. However, the relation
      between left ventricular filling pattern and cardiopulmonary exercise performance
      has not been adequately studied. METHODS: Thirty-one patients with idiopathic (n
      = 14) or ischemic (n = 17) dilated cardiomyopathy, demonstrated by coronary
      angiography, and radionuclide ejection fraction 30.5% +/- 9% underwent
      cardiopulmonary exercise testing with a modified Naughton protocol and a complete
      echocardiographic study. Patients were subdivided into restrictive and
      nonrestrictive groups according to their Doppler transmitral flow pattern. Gas
      exchange data were measured during exercise testing. The relation of left
      ventricular filling pattern to cardiopulmonary parameters was assessed in both
      groups. RESULTS: Exercise duration was similar in the restrictive and
      nonrestrictive groups but significant differences were found in oxygen
      consumption (VO(2)) at peak exercise (14.3 +/- 2.4 vs 20.4 +/- 4.7 mL/kg per
      minute; P <.001) and at the anaerobic threshold (VO(2AT)) (13 +/- 2.2 vs 17.3 +/-
      3 mL/kg per minute; P <.001). Simple linear regression analysis revealed that
      both peak VO(2) and VO(2AT) were significantly correlated with the ratio of peak
      early (E wave) to late (A wave) transmitral filling velocity, early filling
      deceleration time, atrial filling fraction, and A-wave velocity but not with left
      ventricular ejection fraction. Multivariate regression analysis gave only the
      peak A-wave velocity as an independent predictor for both peak VO(2) and VO(2AT).
      CONCLUSIONS: In patients with heart failure, abnormalities of diastolic function
      are the most important determinant of exercise intolerance. A restrictive
      transmitral flow pattern by Doppler echocardiography is a marker of diminished
      cardiopulmonary exercise performance in these patients.

PMID- 10925353
TI  - Intracellular P-glycoprotein expression is associated with the intrinsic
      multidrug resistance phenotype in human colon adenocarcinoma cells.
AB  - The 2 clones, LoVo 5 and LoVo 7, derived from untreated LoVo WT human colon
      adenocarcinoma cells and exhibiting different sensitivity to doxorubicin (DOX),
      were compared in order to identify possible determinants of intrinsic drug
      resistance. A multidrug resistant variant cell line, selected from LoVo WT cells
      by continuous exposure to DOX (LoVo DX), was also included in the study. Analysis
      of the expression and organization of cytoskeletal elements by flow cytometry and
      fluorescence microscopy evidenced a positive correlation between vimentin
      expression and DOX resistance in LoVo 7 and LoVo DX cells, whereas differences in
      actin, tubulin or cytokeratin did not seem to relate to drug response. The
      expression and localization of different drug transporters commonly implicated in
      drug resistance, i.e., the MDR1 gene product P-glycoprotein (P-gp), the multidrug
      resistance-related protein MRP and the lung resistance-related protein LRP were
      also investigated by means of flow cytometry and fluorescence microscopy,
      following labeling with specific monoclonal antibodies. Surface expression of P
      gp was only detected in LoVo DX cells, which also exhibited increased MRP and LRP
      protein levels. However, significant amounts of P-gp were found at intracellular
      sites in the intrinsically resistant LoVo 7 clone. Modulation of P-gp function by
      cyclosporin A was found to alter DOX accumulation and efflux in LoVo 7 cells,
      indicating that intracellular P-gp plays a functional role in drug trafficking
      and suggesting possible implications in determining the intrinsic resistance
      displayed by this clone.

PMID- 10925354
TI  - Apoptotic activity of ursolic acid may correlate with the inhibition of
      initiation of DNA replication.
AB  - Ursolic acid (UA), a pentacyclic triterpene acid, has been reported to exhibit
      anti-tumor activity. In this study, we investigated the pro-apoptotic effect of
      UA on HepG2 human hepatoblastoma cells. Treatment with UA decreased the viability
      of HepG2 cells in a concentration- and time-dependent manner. Furthermore, 30
      microM of UA induced DNA fragmentation and subdiploid cells and enhanced the
      release of cytochrome c and the activation of caspase-3. These results suggest
      that UA induces cell death through apoptosis, which may be mediated by cytochrome
      c-dependent caspase-3 activation. In addition, cell-cycle analysis revealed that
      UA-treated cells were arrested predominantly in the G(0) and G(1) phases with a
      concomitant decrease in the cell population of S phase. Moreover, expression of
      p21(WAF1), a cell-cycle regulator, was increased by UA, indicating that p21(WAF1)
      might mediate UA-induced cell-cycle arrest. However, UA markedly inhibited SV40
      DNA replication in the initiation stage in vitro and significantly reduced the
      DNA cleaving of topoisomerase I and the ssDNA binding activity of replication
      protein A. These results indicate that the inhibition of DNA replication by UA
      may result from blockade of the establishment of the replication fork during
      initiation stage, consequently contributing to UA-induced cell-cycle arrest.
      Taken together, we suggest that UA-induced cell-cycle arrest may be mediated by
      inhibition of DNA replication and the increase of p21(WAF1) expression, which
      induces the release of cytochrome c and the activation of caspase-3, leading to
      apoptosis of HepG2 cells.

PMID- 10925355
TI  - Androgen receptor exon 1 CAG repeat length and risk of ovarian cancer.
AB  - Epidemiological studies indicate that ovarian cancer is an endocrine-related
      tumour. We conducted a case-control comparison to assess the androgen receptor
      (AR) exon 1 polymorphic CAG repeat length (CAG(n)) as a risk factor for
      epithelial ovarian cancer. AR CAG(n) was determined for 319 case subjects with
      ovarian adenocarcinoma and 853 unaffected control subjects (comprising 300
      unrelated adult female monozygotic twins, and 553 adult females sampled randomly
      from the population using the electoral rolls). The CAG(n) distributions of case
      subjects and control subjects were compared as a continuum, and by dichotomising
      alleles according to different CAG(n) cut-points. Logistic regression was used to
      calculate age-adjusted odds ratio (OR) estimates. Analyzed as a continuous
      variable, there was no difference between case subjects and control subjects for
      the smaller, larger or average allele sizes of the CAG(n) genotype, before or
      after adjusting for age. The mean (95% CI) for the average CAG(n) was 22.0 (21.8
      22.2) for case subjects and 22.0 (21.9-22.1) for control subjects (p>.9).
      Analysis of CAG(n) as a dichotomous variable showed no difference between case
      subjects and control subjects for the median cutpoint (>/= 22), or for another
      cut-point previously reported to act as a modifier of breast cancer risk (>/=
      29). Our data provide no evidence for an association between ovarian cancer risk
      and the genotype defined by the AR exon 1 CAG(n) polymorphism, although we cannot
      exclude small effects, or threshold effects in a small subgroup.

PMID- 10925357
TI  - Novel mutations of the von hippel-lindau tumor-suppressor gene and rare DNA
      hypermethylation in renal-cell carcinoma cell lines of the clear-cell type.
AB  - Renal-cell carcinoma (RCC) is the most common neoplasm of the kidney, accounting
      for about 3% of all adult malignancies. Histopathologically, 80% of all cases can
      be classified as clear-cell RCC. Of these, approximately 55% to 70% are
      associated with mutations in the von Hippel-Lindau (VHL) tumor-suppressor gene.
      Here, new mutations of the VHL gene were defined by the use of temperature
      gradient gel electrophoresis and subsequent sequencing. In addition, DNA
      hypermethylation, an alternative mechanism of VHL gene silencing, was evaluated
      by methylation-specific PCR. Twenty-six clear-cell, 3 chromophilic, and 2
      chromophobic RCC cell lines were analyzed. Among the clear-cell RCC cell lines
      tested, 12 (47%) contained 13 mutations overall: 8 (62%) in exon 1, 3 (23%) in
      exon 2, and 2 (15%) in exon 3. Ten of these mutations have thus far not been
      described. All single base pair changes were transversions. Six mutations led to
      alteration of a single amino acid. Seven mutations generated a frameshift or a
      stop codon. One cell line contained a complex duplication of 36 bp. All cell
      lines with mutations showed loss of heterozygosity in the VHL gene. No mutations
      could be detected in the chromophilic or chromophobic RCC samples. Significant
      hypermethylation was not observed in any of the cell lines. These data provide
      further evidence that distinct mutations in the VHL gene are a characteristic
      feature of clear-cell RCC. In contrast, hypermethylation of the gene is probably
      a rare event. The high frequency of transversion mutations suggests a role for
      exogenous carcinogens in the etiology of clear-cell RCCs.

PMID- 10925356
TI  - u-PA and c-MET mRNA expression is co-ordinately enhanced while hepatocyte growth
      factor mRNA is down-regulated in human hepatocellular carcinoma.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) is one of the most important
      humoral mediators of liver regeneration. It is potentially related to molecular
      mechanisms of hepatocarcinogenesis via a paracrine system involving its cellular
      receptor, c-met. In this study, the expression patterns of HGF and c-met were
      evidenced by multiplex RT-PCR in different specimens of human hepatic tissues (n
      = 71). A significant increase of c-met mRNA expression was detected in hepatitis
      (P = 0.001), cirrhosis (P = 0.006), and hepatocellular carcinoma (HCC) tissue (P
      = 0.003) compared with normal parenchyma and steatosis. HGF mRNA expression was
      significantly higher only in hepatitis (P = 0.01). Over-expression of c-met mRNA
      and under-expression of HGF mRNA were detected in the HCCs compared with the
      corresponding peri-tumoral tissues. Neither HGF nor c-met expression was related
      to age, sex, tumor size, grading, presence of pseudocapsula, and proliferative
      activity of the malignant hepatocytes. A significant inverse correlation was
      found between c-met mRNA expression level and survival (in months) of patients (P
      = 0.007), as previously shown for urokinase-type plasminogen activator (u-PA)
      mRNA (P = 0.027). In addition, c-met mRNA expression was strictly associated with
      u-PA mRNA level in HCC samples (P = 0.001). These data show that a loss of
      balance concerning HGF, c-met, and u-PA mRNA expression occurs during
      hepatocarcinogenesis. Particularly, up-regulation of c-met and u-PA mRNA
      transcription appears to be coordinately regulated, and their levels of
      expression are inversely correlated with survival; they must therefore play an
      important role in the development and progression of human HCC and may also be
      relevant prognostic markers.

PMID- 10925358
TI  - Alterations and hypermethylation of the p14(ARF) gene in gastric cancer.
AB  - p14(ARF), generated through an alternative splicing process that replaces the
      first exon, 1alpha, of p16(INK4a) with exon 1beta, located >15 kb upstream of
      exon 1alpha, has been shown to function as a growth suppressor. We examined 11
      gastric cancer cell lines for mRNA expression, homozygous deletion, mutation, and
      promoter methylation of the p14(ARF) gene. No mRNA expression was detected in 5
      of the 7 diffuse-type cell lines. All intestinal cell lines displayed normal
      levels of expression except for one with a low level of expression. Of the 5 cell
      lines without expression, 3 (MKN45, NUGC-2, and NUGC-4) and 1 (KATO III)
      displayed homozygous deletion and methylation of the p14(ARF) gene, respectively.
      No mutation was found in the whole coding region of the p14(ARF) gene in 8 cell
      lines without homozygous deletion. Our results indicate that the p14(ARF) gene is
      more frequently inactivated by homozygous deletion or methylation in diffuse-type
      gastric cancer cell lines (5/7, 71.4%) than in intestinal ones (0/4, P = 0.022).
      When we also analyzed 62 primary gastric cancers for the methylation status of
      the p14(ARF) promoter region, the methylation frequency tended to be higher in
      diffuse-type gastric cancers (15/33, 45.5%) than in intestinal ones (7/28, 25%).
      Thus, p14(ARF) alterations might be involved in diffuse-type gastric
      carcinogenesis.

PMID- 10925359
TI  - High frequencies of circulating melanoma-reactive CD8+ T cells in patients with
      advanced melanoma.
AB  - To determine whether circulating tumor-reactive T cells are present in melanoma
      patients, unstimulated T cells from peripheral blood were tested for recognition
      of HLA-A2- or HLA-A1-matched melanoma cell lines using the ELISPOT assay. Eleven
      out of 19 patients with metastatic melanoma had a T-cell response with up to
      0.81%, 0.78%, 0. 53%, 0.12%, 0.10%, 0.09%, 0.07%, 0.06%, 0.06%, 0.04%, and 0.04%
      of peripheral blood mononuclear cells (PBMC) secreting IFNgamma upon exposure to
      various HLA-A2- or HLA-A1-matched melanoma cell lines. These T-cell responses
      were mediated by CD8+ T cells and could specifically be blocked by an anti-HLA-A2
      antibody in HLA-A2-positive patients. Separation experiments performed in one
      melanoma patient showed tumor-reactive T cells in both the CD8+ effector T cell
      (CD45RA+/IFNgamma+) as well as the CD8+ memory T-cell compartment
      (CD45RO+/IFNgamma+). In 3 out of 5 patients, in whom autologous cell lines were
      available, similar frequencies of T cells in response to HLA-A1- or HLA-A2
      matched allogeneic and autologous tumor cells were observed, while 2 patients had
      a T-cell response restricted to either the autologous or the allogeneic cell
      lines. These results give evidence for the presence of tumor-reactive CD8+ T
      cells in more than half of melanoma patients tested. Although some of these
      patients have clinical evidence for an immunological-mediated tumor control,
      several patients have growing tumors suggesting presence of escape mechanisms.

PMID- 10925360
TI  - Spleen-derived dendritic cells engineered to enhance interleukin-12 production
      elicit therapeutic antitumor immune responses.
AB  - The major goal in cancer immunotherapy is the induction of tumor-specific T
      lymphocytes capable of killing tumor cells. As both dendritic cells (DCs) and
      interleukin-12 (IL-12) can play immunostimulatory roles in vivo, the use of a
      combination of these has become a promising approach. In the present study, we
      used a murine tumor model to examine whether spleen-derived DCs transduced with
      the IL-12 gene could elicit tumor-specific immune responses. BALB/c mice injected
      peritumorally with adenovirus-mediated IL-12 gene-transduced antigen-unpulsed DCs
      inhibited the growth of day 5-established subcutaneous CT26 tumors. Splenocytes
      from treated mice responded specifically to parental tumor cells and showed
      increased production of interferon gamma (IFN-gamma) and antitumor cytotoxic T
      lymphocyte (CTL) activity. Increased numbers of both CD4(+) and CD8(+) T cells
      were detected in the treated tumors. The inhibition of tumor growth was
      significantly greater in mice injected with IL-12 gene-transduced DCs than in
      those injected with IL-12 gene-transduced fibroblasts or the IL-12 gene-encoding
      adenovirus itself. Taken together, these results indicate that DCs transduced
      with the IL-12 gene by a recombinant adenovirus are effective in inducing tumor
      specific Th1 and CTL responses that inhibit the growth of established
      subcutaneous tumors.

PMID- 10925361
TI  - Transfer of IFNgamma-depleted CD4(+) T cells together with CD8(+) T cells leads
      to rejection of murine kidney sarcoma in mice.
AB  - In the murine kidney sarcoma, vaccination with the tumor-specific large T antigen
      induces protective immunity against the tumor. Immunity is dependent both on
      CD8(+) cytotoxic T cells and on CD4(+) T-helper cells. We analyzed whether the
      cytokine phenotype of induced CD4(+) T-effector cells might determine whether or
      not the tumor is successfully rejected. By intracytoplasmic staining of CD4(+)
      cells, IFNgamma-producing (Th1), IL-4-producing (Th2), and IL-10-expressing cells
      could be identified in vaccinated and non-vaccinated animals responding to tumor
      growth. Vaccinated mice rejecting the tumor showed an increase in the percentage
      of IL-4-producing (Th2) cells. In contrast, in non-vaccinated mice succumbing to
      the tumor, the immunosuppressive IL-10-producing cells became more abundant and
      the frequency of IFNgamma-expressing cells dropped at later time points. Yet,
      dominance by either a Th1 or a Th2 response could not be observed. To further
      clarify the relevance of these subsets, Th1 cells were enriched by cell sorting
      according to IFNgamma surface expression. Enriched Th1 and depleted cells, mainly
      consisting of the Th2 phenotype, were transferred together with CD8(+) T cells.
      Surprisingly, immunity could be transferred either with Th1 or Th2 cells, but Th2
      cells were slightly more efficient. This suggests that, at least in the effector
      phase, a Th1 phenotype is not crucial for the rejection. Our findings support the
      view that the Th1/Th2 dichotomy is not central in T-cell-mediated tumor
      rejection.

PMID- 10925362
TI  - Tumor-specific CD4(+) suppressor T-cell clone capable of inhibiting rejection of
      syngeneic sarcoma in A/J mice.
AB  - Elimination of CD4(+) T cells by anti-CD4 antibody caused regression of a
      methylcholanthrene-induced S713a sarcoma growing in syngeneic A/J mice, and the
      tumor regression was essentially required for CD8(+) T cells. A CD4(+) T-cell
      clone, designated T595B1, was established to elucidate the characteristics of
      CD4(+) suppressor T cells. T595B1 expressed CD3, T-cell receptor (TCR)beta, TCR
      Vbeta2, CD4, CD25, CD45RB, CD44, LFA-1, and ICAM-1 molecules on its cell surface
      and showed MHC class II I-E(k)-restricted tumor antigen-specific proliferation.
      T595B1 cells specifically suppressed in vitro CTL induction of S713a in a dose
      dependent manner. Furthermore, culture supernatant of T595B1 cells also
      suppressed in vitro CTL induction, but its suppressive activity was not specific.
      Cytokine analyses revealed that T595B1 cells secreted IL-4, IL-5, IL-6, and IL-10
      but not IFN-gamma, IL-2, TNF, or TGFbeta, indicating that this clone belongs to
      the so-called T helper 2 (Th2) type. However, the suppressive activity of the
      culture supernatant to the in vitro CTL induction was not abrogated by any
      neutralizing antibody to IL-4, IL-5, IL-6, IL-10, or TGF-beta. Repeated adoptive
      transfer of T595B1 cells into syngeneic immune mice entirely impaired their
      capacity to reject S713a sarcoma, resulting in progressive tumor growth in these
      mice.

PMID- 10925363
TI  - Spontaneous mammary carcinomas fail to induce an immune response in syngeneic
      FVBN202 neu transgenic mice.
AB  - FVBN202 mice, which are transgenic for the rat neu gene, spontaneously develop
      mammary carcinomas between 6 and 7 months of age. We investigated whether these
      spontaneous tumors (spontaneous breast carcinoma cells, SBCC) could elicit an
      immune response in naive 6- to 8-week-old FVBN202 transgenic and FVBN
      nontransgenic mice. After s.c. injection of SBCC, the recently activated T cells,
      which were identified by their reduced expression of CD62L (L-selectin), were
      isolated from the draining lymph nodes, expanded with anti-CD3 and IL-2, and
      their cytokine response to tumor cells in vitro was analyzed. Tumor-vaccine
      draining lymph node lymphocytes (TVDLN) from transgenic mice failed to make IFN
      gamma in response to the tumor cells. However, TVDLN from the nontransgenic mice
      exhibited a tumor-specific IFN-gamma response against the SBCC. This indicates
      that the SBCC are immunogenic. The lack of response in transgenic mice could not
      be attributed to cytokine immune deviation or T-cell signaling defects. Although
      transgenic mice were tolerant to their own tumors, their immune competence was
      established by their ability to respond in an allogeneic mixed lymphocyte
      reaction, to reject an allogeneic breast carcinoma cell line, and to produce a
      tumor-specific IFN-gamma response against a syngeneic cancer cell line. This
      transgenic mouse model provides the opportunity to investigate the immune
      response against a primary tumor cell culture rather than cell lines or clones
      and should prove useful for developing immunotherapies that overcome tolerance to
      self-tumor antigens.

PMID- 10925364
TI  - Breaking tolerance to a tumor-associated viral superantigen as a basis for graft
      versus-leukemia reactivity.
AB  - A major goal in tumor immunotherapy consists of breaking potential tumor-specific
      T-cell unresponsiveness (tolerance), which may explain tumor growth in cancer
      patients. We report that immunological tolerance to a tumor-associated viral
      superantigen (SAg) is overcome in a mouse lymphoma model by transfer of
      allogeneic T cells expressing SAg-reactive Vbeta6 T-cell receptor chains.
      Surprisingly, upon contact with SAg-expressing lymphoma cells, Vbeta6 T cells
      became activated rather than tolerized (as reported previously). They also
      developed SAg-specific cytotoxic T-lymphocyte activity and secreted IL-2 and IFN
      gamma. The grafted T cells infiltrated liver metastases, formed close contact
      with SAg-expressing tumor cells, and caused significant graft-vs. -leukemia (GvL)
      effects. Selection for tumor resistance among the progeny from a cross between
      SAg-negative donor and SAg- positive recipient strains revealed a strict
      correlation between loss of the endogenous SAg tolerogen, rescue of Vbeta6 T
      cells from SAg-mediated deletion, and leukemia resistance. These findings suggest
      that immune responses to SAg can be exploited to break tolerance and augment
      immune responses to tumors.

PMID- 10925365
TI  - Thrombin induces apoptosis in human tumor cells.
AB  - Thrombin is a serine protease that is produced during the coagulation process and
      plays an essential role for hemostasis, thrombosis and wound healing. It is a
      potent activator of platelets, induces proliferation of a wide variety of normal
      and malignant human cells, and enhances their invasiveness and metastatic
      potential. We studied the effect of thrombin on the proliferation of a wide
      variety of human tumor cells and report here that, at low concentrations,
      thrombin induces proliferation of these cells. However, at higher concentrations,
      thrombin inhibited their proliferation. We show that this inhibition of cell
      proliferation was due to apoptosis of the tumor cells. The thrombin-mediated
      apoptosis was inhibited significantly by its specific inhibitor, hirudin.
      Furthermore, no consistent pattern of induction and/or modulation of p53, p21 and
      bcl-2 was observed in the thrombin-mediated apoptosis. To our knowledge, this is
      the first report to describe the pro-apoptotic effects of thrombin on human tumor
      cells and may have implications for chemotherapy in cancer patients and for the
      pathogenesis of AIDS as well.

PMID- 10925368
TI  - Interplay between dietary inducers of GST and the GSTM-1 genotype in colon
      cancer.
AB  - The purpose of this study is to determine if cruciferous vegetables and coffee,
      two dietary inducers of glutatione-S-transferases, interact with GSTM-1 genotype
      to alter risk of colon cancer. Data were available on 1579 incident cases of
      adenocarcinoma of the colon and 1898 population-based controls. Intake of
      cruciferous vegetables, specific types of cruciferous vegetable, and coffee were
      not associated with colon cancer; GSTM-1 genotype did not modify these
      associations. However, age at diagnosis and cigarette smoking appeared to be
      important effect modifiers of the associations between GSTM-1, cruciferous
      vegetables and colon cancer. Among GSTM-1 null individuals, <55 years at
      diagnosis, we observed an inverse association between colon cancer and high
      levels of cruciferous vegetable intake relative to people who did not eat
      cruciferous vegetables (ORs 0.23 95% CI 0.10-0.54); broccoli was the cruciferous
      vegetable associated with the strongest inverse association (OR 0.30 95% CI 0.13
      0.70). Among younger individuals who were GSTM-1 present (relative to those with
      GSTM-1 null), we observed an inverse association with colon cancer regardless of
      level of cruciferous vegetable intake (OR 0.74 95% CI 0.30-1.79 for no intake; OR
      0.44 95% CI 0.21-0.92 for <4 servings/week; and OR 0. 44 95% CI 0.19-0.99 for
      >/=4 servings/week). These associations were further modified by cigarette
      smoking. People <65 years of age who smoked had a greater reduction in risk of
      colon cancer from consumption of cruciferous vegetables than non-smokers at the
      same age. In summary, although cruciferous vegetables do not appear to modify
      colon cancer risk in the total population, there are subgroups of the population
      for whom these vegetables may be important. These subgroups are defined mostly by
      age and smoking status.

PMID- 10925366
TI  - In vivo therapy of malignant melanoma by means of antagonists of alphav
      integrins.
AB  - Integrin alphavbeta3 (vitronectin receptor) has been implicated in human
      malignant melanoma progression and angiogenesis as a receptor that provides
      survival signals. However, little is known about the therapeutic potential of
      antagonists of alphavbeta3. In this report, we characterize the activities of 2
      antagonists of alphavbeta3 integrins: a human specific monoclonal antibody (MAb),
      17E6, and a cyclic RGD peptide that blocked cell adhesion and induced detachment
      of previously substrate-attached cells in vitro. In vivo, alphavbeta3 antagonists
      behaved as anti-tumor drugs in a dose- and time-dependent manner. Moreover,
      different therapeutic treatments proved to be effective even in the therapy of
      established macroscopic tumor masses, thus supporting the use of these
      antagonists in clinical therapy. Using a panel of 6 human melanomas and 5
      carcinomas, MAb 17E6 efficiently blocked the in vivo tumor growth of melanomas
      expressing alphavbeta3 as xenografts but did not affect the alphavbeta3-negative
      (although alphav integrin-positive) tumors. This demonstrated that alphavbeta3 is
      a pivotal integrin for the growth of human melanomas. Furthermore, since MAb 17E6
      does not recognize murine alphavbeta3, the effect is due only to the direct anti
      tumor activity and not to the well-known anti-angiogenic activity of alphav
      integrin antagonists. Taken together, our results confirm the essential role of
      alphavbeta3 integrin in the growth of human malignant melanoma in vivo and
      provide strong evidence of the therapeutic potential of alphav-integrin
      antagonists for the treatment of such tumors.

PMID- 10925367
TI  - Gemcitabine, ifosfamide, cisplatin (GIP) for the treatment of advanced non-small
      cell lung cancer: a phase II study of the italian oncology group for clinical
      research (GOIRC).
AB  - The purpose of this study was to evaluate the activity and the toxicity of the
      combination of gemcitabine with ifosfamide and cisplatin (GIP) in chemonaive
      patients with advanced non small cell lung cancer (NSCLC). Eighty chemonaive
      patients with Stage IIIB-IV NSCLC were treated with the combination of
      gemcitabine 1 g/m(2) on Days 1 and 8, ifosfamide 2 g/m(2) on Day 1 and cisplatin
      80 mg/m(2) on Day 2. Cycles were administered on an outpatient basis every 3
      weeks. Hematologic toxicity was the main side effect; Grade III-IV
      thrombocytopenia was observed in 54 (67%) patients and Grade III-IV leucopenia in
      44 (55%) patients, with 4 episodes of febrile neutropenia and 1 toxic death.
      Thirteen patients received platelet transfusions and 38 were transfused with
      packed red cells. All patients were evaluable for response. The overall response
      rate was 54% (95% confidence interval 43 to 65%) with 1 complete response. In
      patients with Stage IIIB and IV disease, response rates were 58% and 52%,
      respectively. Median time to progression was 40 weeks (range 0-114) and median
      overall survival was 12 months (16.6 months for stage IIIB and 10.4 months for
      stage IV). Median and minimum follow-up were 19 and 12 months, respectively. The
      GIP combination shows a response rate and overall survival of clinical interest.
      Hematologic toxicity was the main toxic effect, especially in patients with low
      performance status. This regimen will be tested in a Phase III randomized trial.

PMID- 10925369
TI  - Role of alcohol dehydrogenase 3 and cytochrome P-4502E1 genotypes in
      susceptibility to cancers of the upper aerodigestive tract.
AB  - Alcohol is a recognized risk factor for upper aerodigestive tract (UAT) cancers,
      but the mechanism by which alcohol causes cancer remains obscure. Ethanol is
      oxidized to acetaldehyde (the suspected carcinogenic agent in alcohol) by alcohol
      dehydrogenases (ADHs) and cytochrome P-4502E1 (CYP2E1), both of which exhibit
      great inter-individual variability in activity. The hypothesis that these
      polymorphisms influence susceptibility to alcohol-related cancers remains poorly
      documented. We investigated whether ADH(3) and CYP2E1 DraI and RsaI genotypes
      modified the risk of UAT cancers among 121 oral cavity/pharyngeal cancer
      patients, 129 laryngeal cancer patients, and 172 controls, all French Caucasians.
      Cancer risks and gene-alcohol interactions were analyzed by unconditional
      logistic regression, accounting for potential confounders. ADH(3) genotype was
      not associated with UAT cancer. In contrast, a 2-fold risk of oral
      cavity/pharyngeal (OR = 2.0, 95% CI 1.0-3.9) and laryngeal (OR = 1.8, 95% CI 1.0
      3.5) cancers was observed for carriers of the CYP2E1 DraI C variant allele
      compared with other individuals. The risk associated with the CYP2E1 RsaI c2
      variant allele also increased for oral cavity/pharyngeal cancer (OR = 2.6, 95% CI
      1.0-6. 6). The effects of ADH(3) or CYP2E1 genotype and alcohol or tobacco were
      independent. The highest risk of oral cavity/pharyngeal cancer was observed among
      the heaviest drinkers (>80 g/day) with the CYP2E1 DraI C allele (OR = 5.8, 95% CI
      1.9-18.2) or the CYP2E1 RsaI c2 allele (OR = 7.2, 95% CI 1.4-38.2) compared with
      lighter drinkers with other genotypes. Our study suggests that CYP2E1 genotype
      modifies the risk of UAT cancers, but due to the low frequency of CYP2E1 variant
      alleles, large-scale studies are needed to confirm our findings.

PMID- 10925370
TI  - Effect of interferon therapy on the incidence of hepatocellular carcinoma and
      mortality of patients with chronic hepatitis C: a retrospective cohort study of
      738 patients.
AB  - The effect of interferon on the long-term clinical outcome of patients with
      chronic hepatitis C remains unclear. This study included 594 patients with
      chronic hepatitis C who received interferon-alpha therapy (Interferon group) and
      144 patients with chronic hepatitis C who did not receive interferon (Control
      group). The patients in the Interferon group were classified into the following
      three groups based on the response of the serum aminotransaminase level of the
      patient during and after completion of the therapy protocol: sustained responders
      (n = 175), transient responders (n = 165), and non-responders (n = 254). The age,
      sex, serum aminotransaminase level, platelet count, histological staging,
      hepatitis C virus (HCV) subtype, and HCV concentration at baseline were adjusted
      with the Cox proportional hazards model. The length of follow-up for assessment
      of the risk for developing hepatocellular carcinoma (HCC) was 57.2 +/- 13.9
      months in the Interferon group and 67.7 +/- 28.7 months in the Control group.
      Multivariate analysis showed that interferon therapy decreased the risk for
      developing HCC by 48% compared with that in the Control group (P = 0.064). The
      older the age, being male, having a low platelet count, and higher histological
      stage were independent factors associated with the development of HCC. The hazard
      rate ratio for development of HCC in the sustained responders, transient
      responders, and non-responders was 0.16 (95% confidence interval [CI]: 0.04
      0.62), 0.27 (95% CI: 0. 09-0.79), and 0.74 (95% CI: 0.37-1.48), respectively.
      During follow-up, 18 patients in the Interferon group died (10 from liver-related
      diseases) and 17 patients in the Control group died (10 from liver-related
      diseases). No sustained responder or transient responder in the Interferon group
      died of liver-related disease. The cumulative survival rates of the Interferon
      and Control groups were nearly identical during the first 5 years following
      diagnosis. Thereafter, the cumulative survival rate of the Control group
      declined, resulting in an 8-year survival rate in the Interferon and Control
      groups of 97% and 81%, respectively (P = 0. 061). Similar trends were seen in the
      survival analysis of those who had died of liver disease: the 8-year survival
      rates of the Interferon and Control groups were 98% and 88%, respectively (P = 0.
      32). Our study demonstrated that interferon therapy significantly lowered the
      incidence of HCC among patients with chronic hepatitis C who showed sustained
      normalization and among patients who showed transient normalization of the serum
      aminotransferase level after completion of interferon therapy. The survival
      analyses and determination of cause of death suggested that interferon therapy
      improves the long-term survival of chronic hepatitis C patients who respond to
      this therapy, possibly by decreasing mortality from liver-related diseases.

PMID- 10925372
TI  - Hereditary cancer, creativity and peer review.

PMID- 10925371
TI  - Antioxidants and cancers of the esophagus and gastric cardia.
AB  - Antioxidant vitamins have attracted considerable attention in previous studies of
      esophageal squamous-cell carcinoma, but dietary studies of adenocarcinoma of the
      esophagus and gastric cardia remain sparse. Treating these tumors as distinct
      diseases, we studied intakes of vitamin C, beta-carotene and alpha-tocopherol in
      a nationwide population-based case-control study in Sweden, with 185, 165, and
      258 cases of esophageal adenocarcinoma, esophageal squamous-cell carcinoma, and
      gastric cardia adenocarcinoma, respectively, and 815 controls. Subjects with a
      high parallel intake of vitamin C, beta-carotene, and alpha-tocopherol showed a
      40-50% decreased risk of both histological types of esophageal cancer compared
      with subjects with a low parallel intake. Antioxidant intake was not associated
      with the risk of gastric cardia adenocarcinoma. Separately, vitamin C and beta
      carotene reduced the risk of esophageal cancers more than alpha-tocopherol. We
      found that antioxidant intake is associated with similar risk reductions for both
      main histological types of esophageal cancer. Our findings indicate that
      antioxidants do not explain the diverging incidence rates of the 2 histological
      types of esophageal cancer. Moreover, our data suggest that inverse associations
      with esophageal squamous-cell carcinoma and adenocarcinoma may be stronger among
      subjects under presumed higher oxidative stress due to smoking or
      gastroesophageal reflux, respectively. Our results may be relevant for the
      implementation of focused, cost-effective preventive measures.

PMID- 10925373
TI  - Reply to fusaro

PMID- 10925374
TI  - Seventh Japanese-German workshop on molecular and cellular aspects of
      carcinogenesis.

PMID- 10925375
TI  - Klippel-Trenaunay syndrome.

PMID- 10925376
TI  - Kallmann syndrome in three unrelated women and an association with femur-fibula
      ulna dysostosis in one case.
AB  - We describe three unrelated women with hypogonadotropic hypogonadism and anosmia;
      that is, Kallmann syndrome. Absence of olfactory bulbs and tracts and different
      degrees of asymmetric dysplasia of olfactory sulci were demonstrated by MRI. Both
      the father of Case 1 and the maternal aunt of Case 3 had anosmia, thus autosomal
      dominant inheritance seems to be likely. Patient 2 had Kallmann syndrome and FFU
      (femurfibula-ulna) dysostosis as a sporadic occurrence in her family.

PMID- 10925377
TI  - Early death in two sisters with Hennekam syndrome.
AB  - We report on two sisters with facial anomalies, protein-losing enteropathy, and
      intestinal lymphangiectasia consistent with the diagnosis of Hennekam syndrome.
      Both patients had a number of other anomalies not previously described in this
      autosomal recessive disorder, i.e., primary hypothyroidism, hypertrophic pyloric
      stenosis, and an early fatal outcome. These cases support the autosomal recessive
      transmission and the expansion of the phenotype of the Hennekam syndrome.

PMID- 10925378
TI  - Mutations in the KCNQ4 K+ channel gene, responsible for autosomal dominant
      hearing loss, cluster in the channel pore region.
AB  - The DFNA2 locus for autosomal dominant nonsyndromic hearing impairment on
      chromosome 1p34 contains at least 2 genes responsible for hearing loss, GJB3 and
      KCNQ4. GJB3 is a member of the connexin gene family and KCNQ4 is a voltage-gated
      potassium channel. KCNQ4 mutations were first found in a French family, and later
      also in a Belgian, an American and two Dutch families. Here we present the
      analysis of the GJB3 and KCNQ4 genes in a third Dutch family linked to DFNA2. No
      mutation was found in GJB3, but a missense mutation changing a conserved Leu
      residue into His (L274H) was found in the coding region of the KCNQ4 gene in all
      patients of this DFNA2 family. Examination of the position of all known KCNQ4
      mutations showed a clustering of mutations in the pore region of the KCNQ4 gene,
      responsible for the ion selectivity of the channel. The clustering of mutations
      in this domain confirms its importance.

PMID- 10925379
TI  - Periconceptional intake of vitamin supplements and risk of multiple congenital
      anomalies.
AB  - Numerous studies have reported reduced risks for a variety of single congenital
      anomaly phenotypes associated with maternal periconceptional use of vitamin
      supplements containing folic acid. Here we investigated whether periconceptional
      use of vitamin supplements containing folic acid by women altered their risk for
      delivering infants with multiple congenital anomalies (MCAs). Data were derived
      from a case-control study representing deliveries (fetal deaths and infants) from
      2 California counties between January 1993 and July 1996. MCAs were defined as 2
      or more congenital anomalies affecting more than one organ system or a major
      anomaly in combination with 2 minor anomalies. Controls were randomly selected
      from nonmalformed live-born infants. Telephone interviews were conducted with 112
      (73.7% of eligible) case and 195 (78.0% of eligible) control mothers. Compared to
      women who did not use multivitamin supplements containing folic acid in the
      period 3 months before through 3 months after conception, women who used in this
      time period were observed to have an elevated risk to deliver fetuses or infants
      with MCAs, odds ratio = 2.6 (95% confidence interval 1.1-6.2). This elevated risk
      was not substantially altered (adjusted odds ratio = 2.9 [0.8-10.3]) by adjusting
      for maternal race/ethnicity, education, gravidity, body mass index, alcohol
      consumption, and cigarette smoking. No particular organ system seemed to be
      uniquely represented among the MCA fetuses and infants whose mothers used vitamin
      supplements. The observed elevated risk associated with maternal vitamin use is
      considered to be preliminary and needs to be replicated in other populations.

PMID- 10925380
TI  - Autosomal recessive multiple pterygium syndrome: a new variant?
AB  - Multiple pterygium syndromes include at least 15 different entities characterized
      by multiple pterygia or webs of the skin and multiple congenital anomalies. We
      describe a female infant who presented with a distinct constellation of multiple
      anomalies consisting of pterygia of the inguinal, intercrural and popliteal
      areas, flexion contractures and arthrogryposis of some joints, craniofacial
      anomalies including ectropion, medial canthal web, blepharophimosis, hypoplasia
      of nose, oral and nasopharyngeal cavities, vocal cords and tongue, micrognathia,
      orolabial synechiae secondary to pterygia, low set ears, alopecia, sad and
      expressionless face, short neck, asymmetric nipples, anal stenosis, rectal polyp,
      hypoplastic labia majora, complete syndactyly of all fingers and toes, pes
      equinovarus, bandlike web between feet, and absence of the nails and phalangeal
      palmar creases. Radiological examination showed synostosis, absence or hypoplasia
      of metacarpal, metatarsal and phalangeal bones on feet and hands, and hypoplasia
      of pelvic bones and scapulae. This pattern of anomalies does not fit entirely any
      of the known multiple pterygium syndromes. Autosomal recessive inheritance is
      most likely due to the presence of three similarly affected siblings and normal
      parents.

PMID- 10925382
TI  - Population screening for cystic fibrosis: a research agenda for the next 10
      years.

PMID- 10925381
TI  - Population screening for cystic fibrosis in Western Australia: community
      response.
AB  - We measured acceptance of carrier testing for cystic fibrosis in the community
      when offered in a primary care setting, determined variables influencing
      acceptance, and assessed knowledge of cystic fibrosis 3-6 months later. A total
      of 5,102 individuals age 18-50 years attending general practices or a family
      planning clinic in Western Australia completed questionnaires about knowledge of
      cystic fibrosis and the State Anxiety Inventory. Testing for the delta F508 gene
      was offered. After 3-6 months, carriers, a sample of consenting participants who
      were not tested, and a sample of test-negative participants were sent a further
      questionnaire; 43.5% of participants chose to be tested for cystic fibrosis
      carrier status. Women, younger people, people with higher education, people
      without children, and people planning to have children were more likely to be
      tested. After 3-6 months, carriers gave correct responses to questions about
      cystic fibrosis more frequently than those who tested negative or were not
      tested; 82.2% of carriers knew that they were definitely a carrier and 31.1% of
      test-negative individuals believed they were definitely not carriers. Thus,
      population carrier screening for cystic fibrosis offered in a community setting
      in Western Australia was acceptable to almost half of those offered testing,
      particularly younger people and those planning to have children, for whom
      knowledge of carrier status could be useful in making reproductive decisions.
      There was evidence that tested individuals recalled information in a way that
      minimised their risk of being a carrier.

PMID- 10925383
TI  - Complete maternal isodisomy of chromosome 8 in an individual with an early-onset
      ileal carcinoid tumor.
AB  - Uniparental disomy (UPD) is a condition in which diploid individuals possess a
      chromosome pair from a single parent. In some instances, UPD causes an abnormal
      phenotype due to imprinting effects, reduction to homozygosity at recessive
      disease loci, or trisomy mosaicism. Here we report the first account of an
      individual with apparently nonmosaic complete maternal isodisomy of chromosome 8.
      This individual was identified during routine genotyping in a genomewide search
      for type 2 diabetes susceptibility genes, although he does not have diabetes. He
      is of normal appearance, stature, and intelligence, but there is an unusual
      history of early onset ileal carcinoid. The discovery of other maternal UPD 8
      cases will be necessary to define whether this condition causes a distinct
      phenotype.

PMID- 10925384
TI  - Compound heterozygous patient with glycogen storage disease type III:
      identification of two novel AGL mutations, a donor splice site mutation of
      Chinese origin and a 1-bp deletion of Japanese origin.
AB  - Glycogen storage disease type III (GSD III) is an autosomal recessive disorder
      caused by deficiency of glycogen-debranching enzyme (AGL). We studied a 2-year
      old GSD III patient whose parents were from different ethnic groups. Nucleotide
      sequence analysis of the patient showed two novel mutations: a single cytosine
      deletion at nucleotide 2399 (2399delC) in exon 16, and a G-to-A transition at the
      +5 position at the donor splice site of intron 33 (IVS33+5G>A). Analysis of the
      mRNA produced by IVS33+5G>A showed aberrant splicing: skipping of exon 33 and
      activation of a cryptic splice site in exon 34. Mutational analysis of the family
      revealed that the 2399delC was inherited from her father, who is of Japanese
      origin, and the IVS33+5G>A from her mother, who is of Chinese descent,
      establishing that the patient was a compound heterozygote. To our knowledge, this
      is the first report of a mutation identified in a GSD III patient from the
      Chinese population.

PMID- 10925385
TI  - Third Prader-Willi syndrome phenotype due to maternal uniparental disomy 15 with
      mosaic trisomy 15.
AB  - We report on a boy with mosaicism for trisomy 15 and Prader-Willi syndrome (PWS)
      due to maternal isodisomy for chromosome 15. His phenotype is consistent with PWS
      and trisomy 15 mosaicism. Although our patient is unusual in having maternal
      isodisomy rather than the more common maternal heterodisomy, we think that his
      more severe PWS phenotype is due to his trisomy 15 mosaicism rather than to
      homozygosity for deleterious chromosome 15 genes. We propose that individuals
      with PWS have one of three similar but distinctive phenotypes depending on the
      cause of their condition. Patients with paternal deletions have the typical PWS
      phenotype, patients with maternal UPD have a slightly milder phenotype with
      better cognitive function, and those with maternal UPD and mosaic trisomy 15 have
      the most severe phenotype with a high incidence of congenital heart disease.
      These phenotype-genotype differences are useful to guide the work-up of patients
      with suspected PWS and to provide prognostic counseling for families.

PMID- 10925386
TI  - Cardio-facio-cutaneous syndrome phenotype in an individual with an interstitial
      deletion of 12q: identification of a candidate region for CFC syndrome.
AB  - We report on a 19-month-old girl who presented with the phenotype of cardio
      faciocutaneous (CFC) syndrome including characteristic minor facial anomalies,
      cardiac defect, ectodermal anomalies, and developmental delay. Cytogenetic
      analysis showed the presence of an interstitial deletion of one chromosome 12,
      del(12)(q21.2q22), confirmed by fluorescence in situ hybridization with
      chromosome band specific probes. Controversy exists as to whether CFC and Noonan
      syndrome (NS) are distinct disorders, a contiguous gene syndrome, or allelic
      variants. The identification of the del(12) in this patient, in a region distinct
      from the putative NS locus, supports the view that CFC is a genetically distinct
      condition from NS. In addition, this implicates the region 12q21.2-->4q22 as a
      candidate region for the gene(s) causing CFC syndrome.

PMID- 10925387
TI  - Novel assay for Roberts syndrome assigns variable phenotypes to one
      complementation group.
AB  - Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by
      heterogeneous clinical features, the most notable being tetraphocomelia, cleft
      lip, and cleft palate. Cells derived from most RS patients exhibit abnormal
      cytogenetic and cellular phenotypes that include the premature separation of para
      and pericentromeric heterochromatin visible on C-banded metaphase chromosomes, a
      phenomenon referred to as heterochromatic splaying. Previously, it was shown that
      these abnormal phenotypes can be complemented following somatic cell
      hybridization between RS cells and control cells. In the current study, a
      permanent cell line was established from a new RS patient with a more severe
      phenotype than represented by previously established cells in culture. With a
      newly developed assay designed to facilitate rapid evaluation of in vitro
      complementation, we assigned this new patient to the same genetic complementation
      group defined by other, less severely affected patients. The results demonstrate
      that a single complementation group defines RS patients with heterochromatic
      splaying regardless of clinical severity.

PMID- 10925388
TI  - Case of 45,X/46,XY mosaicism with non-mosaic discordance between short-term villi
      (45,X) and cultured villi (46,XY).
AB  - We report on a prenatally detected case of discordant non-mosaic karyotypes
      following chorionic villus sampling. A 45,X karyotype was found in
      cytotrophoblast cells and a 46,XY karyotype in mesenchymal core cells. A
      subsequent amniocentesis showed a true 45,X/46,XY mosaicism. Confirmatory
      studies, including fluorescence in situ hybridization (FISH) in various fetal and
      placental tissues as well as in the original villi preparations changed the
      presumed condition of generalized mosaicism with culture confined normality to
      that of generalized mosaicism with absolute concordance. This case underscores
      the importance of the investigation of both short-term and cultured villi
      preparations, the implementation of prenatal FISH studies, and the need for
      thorough follow-up investigation in cases of discrepant results.

PMID- 10925389
TI  - Multiple meningiomas, craniofacial hyperostosis and retinal abnormalities in
      Proteus syndrome.
AB  - Because clinical evidence suggests that Proteus syndrome may be caused by a
      somatic mutation during early development, resulting in mosaicism, the possible
      types of abnormalities and their clinical distributions are highly variable.
      Here, we report on an unusual patient with Proteus syndrome. Manifestations
      included multiple meningiomas, polymicrogyria, and periventricular heterotopias.
      Both eyes had epibulbar cystic lesions. The retina showed diffuse disorganization
      with nodular gliosis, retinal pigmentary abnormalities, chronic papilledema, and
      optic atrophy. Other abnormalities included progressive cranial, mandibular,
      maxillary, and auditory canal hyperostoses, epidermal nevi, and mental
      deficiency. The limbs were proportionate, and the hands and feet were normal.

PMID- 10925390
TI  - Candidate region for Coffin-Siris syndrome at 7q32-->34.
AB  - Coffin-Siris syndrome is characterized by intrauterine growth retardation, mental
      deficiency, coarse face, hypoplastic fifth fingers and nails, hirsutism, and
      initial difficulties with feeding. The etiology of this syndrome is unknown. We
      report on an 11-year-old girl with Coffin-Siris syndrome and a de novo,
      apparently balanced reciprocal translocation between chromosomes 7 and 22
      [t(7;22)(q32;q11.2)]. The 7q breakpoint in our patient is very similar to the
      breakpoint reported in a previous case [McPherson et al., 1997: Am J Med Genet
      71:430-433] with a balanced t(1;7)(q21.3;q34). Together, these patients provide
      evidence that the region 7q32-->34 is a candidate region for the gene responsible
      for Coffin-Siris syndrome.

PMID- 10925391
TI  - Further evidence for autosomal dominant inheritance and ectodermal abnormalities
      in Kabuki syndrome.
AB  - Most cases with Kabuki syndrome (KS) were reported sporadically. Recently, a few
      familial cases of KS were reported. This report provides further evidence that
      the KS is inherited as a dominant trait with variable expressivity. The proposita
      is an 18-month-old girl with facial findings characteristic of Kabuki syndrome,
      prominent fingertip-pads, a midsagittal cleft of vertebral body D4, hypotonia,
      and psychomotor retardation. Her mother had a similar facial appearance,
      prominent, cup-shaped ears, an abnormal dentition, early breast development, and
      low-normal intelligence. Because mother and daughter both had evident Kabuki
      syndrome, we conclude that KS in this family is inherited as a dominant trait.
      Further family history supports this finding. Microscopic examination of the hair
      of the proposita shows abnormalities consisting of trichorrhexis nodosa, twisting
      of the hairshafts, and irregularity of the diameter of the hair, as was described
      recently in a patient with KS. This could be another occasional finding in this
      syndrome, but further studies are required. The presence of abnormal hair, nails,
      and the commonly described tooth abnormalities in KS further suggest ectodermal
      involvement in this syndrome.

PMID- 10925392
TI  - Severe hypodontia and oral xanthomas in Alagille syndrome.

PMID- 10925393
TI  - Maternal caffeine and its effect on the fetus.

PMID- 10925394
TI  - A review of antimycobacterial natural products.
AB  - Tuberculosis is a chronic infectious disease caused by several species of
      mycobacteria. Due to multi-drug resistant strains of mycobacteria and to a high
      prevalence of tuberculosis in patients who have acquired human immunodeficiency
      syndrome (AIDS), the number of patients infected with the disease is increasing
      worldwide. Thus there is an urgent need for new effective antimycobacterial
      agents to replace those currently in use. In this instance, the plant kingdom is
      undoubtedly a valuable source for new anti-tuberculosis agents. The present
      review article reports the findings from an extensive literature search of all
      plants that have been assessed for antimycobacterial/antitubercular activity over
      the past 20-30 years. An attempt has been made to summarize the information in
      order to highlight those promising plant species which are worthy of further
      investigation as leads for drug development. Over 350 plant species from a wide
      range of families and origins, containing various chemical classes of compounds,
      have been screened for such activity. A review of the relevant in vitro assays
      using different species of pathogenic and non-pathogenic mycobacteria is also
      included.

PMID- 10925395
TI  - Antioxidant activity of Nigella sativa essential oil.
AB  - The essential oil of black cumin seeds, Nigella sativa L., was tested for a
      possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC
      screening methods, showed that thymoquinone and the components carvacrol, t
      anethole and 4-terpineol demonstrated respectable radical scavenging property.
      These four constituents and the essential oil possessed variable antioxidant
      activity when tested in the diphenylpicrylhydracyl assay for non-specific
      hydrogen atom or electron donating activity. They were also effective.OH radical
      scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes
      and the deoxyribose degradation assay. GC-MS analysis of the essential oil
      obtained from six different samples of Nigella sativa seeds and from a commercial
      fixed oil showed that the qualitative composition of the volatile compounds was
      almost identical. Differences were mainly restricted to the quantitative
      composition.

PMID- 10925396
TI  - Detection of antifungal activity in Portulaca oleracea by a single-cell bioassay
      system.
AB  - The antifungal activity of Portulaca oleracea extracts against hyphal growth of
      various fungi was evaluated in real time using an automatic single-cell bioassay
      system. Target organisms were the filamentous fungi Aspergillus and Trichophyton
      and the yeast Candida. A colony of test fungi was in contact with the assay
      medium, or assay medium containing plant extract, in sequence. The antifungal
      activity of each fraction of P. oleracea was evaluated based on the dynamic
      hyphal growth response curves of test fungi. A crude sample obtained by EtOAc
      extract showed a specific and marked activity against dermatophytes of the genera
      Trichophyton.

PMID- 10925397
TI  - A phase I trial of andrographolide in HIV positive patients and normal
      volunteers.
AB  - A phase I dose-escalating clinical trial of andrographolide from Andrographis
      paniculata was conducted in 13 HIV positive patients and five HIV uninfected,
      healthy volunteers. The objectives were primarily to assess safety and
      tolerability and secondarily to assess effects on plasma virion HIV-1 RNA levels
      and CD4(+) lymphocyte levels. No subjects used antiretroviral medications during
      the trial. Those with liver or renal abnormalities were excluded. The planned
      regimen was 5 mg/kg bodyweight for 3 weeks, escalating to 10 mg/kg bodyweight for
      3 weeks, and to 20 mg/kg bodyweight for a final 3 weeks. The trial was
      interrupted at 6 weeks due to adverse events including an anaphylactic reaction
      in one patient. All adverse events had resolved by the end of observation. A
      significant rise in the mean CD4(+) lymphocyte level of HIV subjects occurred
      after administration of 10 mg/kg andrographolide (from a baseline of 405
      cells/mm(3) to 501 cells/mm(3); p = 0.002). There were no statistically
      significant changes in mean plasma HIV-1 RNA levels throughout the trial.
      Andrographolide may inhibit HIV-induced cell cycle dysregulation, leading to a
      rise in CD4(+) lymphocyte levels in HIV-1 infected individuals.

PMID- 10925398
TI  - Protective effects of boldine against free radical-induced erythrocyte lysis.
AB  - Boldine, an aporphine alkaloid extracted from the leaves and bark of boldo
      (Peumus boldus Mol.), has been shown to exhibit strong free-radical scavenger and
      antioxidant properties. Here, we report the in vitro ability of boldine to
      protect intact red cells against the haemolytic damage induced by the free
      radical initiator 2, 2'-azobis-(2-amidinopropane) (AAPH). Boldine concentration
      dependently prevented the AAPH-induced leakage of haemoglobin into the
      extracellular medium. Substantial and similar cyto-protective effects of boldine
      were observed whether the antioxidant was added 1 h prior to, or simultaneously
      with, the azo-compound. The delayed addition of boldine, by 1 h relative to AAPH,
      diminished but did not abolish its cytoprotective effect. However, negligible
      effects of boldine were observed after its addition to erythrocytes previously
      incubated with AAPH for 2 h. The data presented demonstrate that, in addition to
      its well-established antioxidant effects, boldine also displays time-dependently
      strong cytoprotective properties against chemically induced haemolytic damage.

PMID- 10925399
TI  - Screening for the antidepressant activity of some species of Hypericum from South
      Brazil.
AB  - The crude methanol extracts of three species of the genus Hypericum (H.
      brasiliense, H. caprifoliatum and H. myrianthum) native to South Brazil were
      evaluated for the antidepressant activity according to the forced swimming test,
      a classical animal model for antidepressant drug screening. Among the species
      studied, only H. caprifoliatum showed activity. Thus, this plant was fractionated
      with solvents in increasing polarity (petroleum ether; petroleum ether:
      chloroform (1:1); chloroform and methanol). The petroleum ether fraction was the
      only one which demonstrated antidepressant activity at a dose of 270 mg/kg/day
      (i.p.). The chemical analyses showed that this fraction is rich in phenolic
      compounds, mainly of the phloroglucinol type.

PMID- 10925401
TI  - Stabilization of lysosomal membrane and cell membrane glycoprotein profile by
      Semecarpus anacardium linn. nut milk extract in experimental hepatocellular
      carcinoma.
AB  - Semecarpus anacardium Linn. nut milk extract administered orally at a dose of 200
      mg/kg/day for 14 days exerted an in vivo stabilizing effect on lysosomal membrane
      and glycoprotein content in rat hepatocellular carcinoma. This was demonstrated
      in normal rats and in animals whose biomembranes were rendered fragile by
      induction of hepatocellular carcinoma with aflatoxin B(1) and subsequent
      treatment with Semecarpus anacardium nut extract. In this condition, the
      discharge of lysosomal enzymes increased significantly with a subsequent increase
      in glycoprotein components. The nut extract administration reversed these adverse
      changes to near normal in treated animals. The possible reason for this reversal
      is discussed. Such stabilization of biomembranes by Semecarpus anacardium nut
      extract may have a beneficial effect in the treatment of hepatocellular carcinoma
      and other cancers involving abnormal fragility of lysosomes and glycoprotein
      content providing the extract demonstrates safety in a full toxicity study.

PMID- 10925400
TI  - Chemopreventive activity of quercetin during carcinogenesis in cervix uteri in
      mice.
AB  - The chemopreventive action of quercetin was examined during 20-methyl
      cholanthrene induced cervical neoplasia in virgin Swiss albino mice. The effects
      were evaluated on the basis of histopathological observation of the cervical
      epithelium, micronucleus frequency in vaginal exfoliated cells and some
      biochemical parameters in the host liver. Quercetin was found to arrest or
      reverse the progression of cervical neoplasia. The micronucleus frequency was
      reduced following its administration. The potential anti-carcinogenic effect of
      quercetin noted in this study is attributed to its antioxidant property which was
      reflected in the lipid peroxides and their role in the host detoxification
      system, as expressed in liver glutathione level, glutathione-S-transferase,
      glutathione peroxidase, catalase and superoxide dismutase activity. As an
      integral part of the diet quercetin may offer protection to the epithelium from
      the damaging effects of carcinogenic chemicals.

PMID- 10925402
TI  - Antiplasmodial and antiamoebic activities of medicinal plants from Sierra Leone.
AB  - Crude ethanol extracts of 18 medicinal plants from Sierra Leone, West Africa were
      examined for antiplasmodial activity against Plasmodium falciparum, using an in
      vitro microtest. Eleven of these extracts were also screened for in vitro
      antiamoebic activity against Entamoeba histolytica. Only one plant extract,
      Triclisia patens (Menispermaceae) showed significant antiplasmodial activity
      (IC(50) = 8 microg/mL). None of the plant extracts was effective against
      Entamoeba histolytica.

PMID- 10925403
TI  - Acute and subacute toxicity of Cochlospermum regium (Mart. & Schr.) pilger.
AB  - The toxicity of a hydroethanol extract of the subterranean part of Cochlospermum
      regium was evaluated in mice and rats. The extract had moderate acute toxicity
      when administered intraperitoneally and low toxicity upon oral administration. A
      subacute toxicity test revealed that the extract is well tolerated by these
      animals.

PMID- 10925404
TI  - Free radical scavenging and membrane protective effects of methanol extracts from
      Anthriscus cerefolium L. (Hoffm.) and Petroselinum crispum(Mill.) nym. ex A.W.
      Hill.
AB  - The antilipoperoxidant activity of Anthriscus cerefolium L. (Hoffm.), chervil,
      Petroselinum crispum (Mill.) Nym. ex A. W. Hill., parsley extracts were evaluated
      with ascorbic acid induced lipid peroxidation on rat brain homogenates. These
      results are completed by the antiradical potential of these extracts against a
      solution of OH. radical. In all cases luteolin-7-O-glucoside was used as a
      reference material.

PMID- 10925405
TI  - Molluscicidal properties of glycoalkaloid extracts from Moroccan solanum species.
AB  - The glycoalkaloid extracts of seeds and leaves of Solanum sodomaeum and berries
      of Solanum elaeagnifolium were shown to have molluscicidal activity against
      Bulinus truncatus.

PMID- 10925406
TI  - Evaluation of the antimicrobial property of the stem bark of Picralima nitida
      (Apocynaceae).
AB  - The basic fraction (BF) of the methanol extract of the stem bark of Picralima
      nitida (family Apocynaceae) exhibited significant antimicrobial activity against
      a wide range of Gram-positive bacteria and fungi, but limited activity against
      Gram-negative bacteria. The BF had a similar minimum inhibitory concentration
      (MIC) for S. aureus to the control drug ampicillin, and lower MIC values against
      A. flavus and A. niger than those of tiaconazole. Values of the minimum
      bactericidal concentration (MBC) of the BF against microorganisms tested were
      generally much higher than those for the control drugs ampicillin and gentamicin.
      The results suggest that some constituents of the stem bark could be isolated and
      developed into effective antimicrobial agents.

PMID- 10925407
TI  - Antimicrobial constituents of the leaves of Acalypha wilkesiana and Aacalypha
      hispida.
AB  - An activity directed fractionation of a 50% aqueous ethanol extract of A.
      wilkesiana and A. hispida leaves resulted in the isolation of gallic acid,
      corilagin and geraniin as the compounds responsible for the observed
      antimicrobial activity. Quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside
      were also isolated from the inactive fraction of A. hispida. The structures were
      established by permethylation, 2D - NMR ((1)H and (13)C) and MS data.

PMID- 10925408
TI  - The ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine
      induced amnesia in rats.
AB  - Ameliorating effects were investigated of the cognitive-enhancing Chinese herbs
      administered orally for 1 week-Panax ginseng (PG), Panax notoginseng (PNG),
      Dioscorea opposita (DO), Gastrodia elata (GE), Salvia miltiorrhiza (SM), Acorus
      gramineus (AG), Coptis chinensis (CC), Polygonum multiflorum (PM), Cyperus
      rotundus (CR) and Psoralea corylifolia (PC)-on the scopolamine (SCOP)-induced
      amnesia by using a passive avoidance task in rats. Of ten Chinese herbs, only PG,
      PNG, GE and CC prolonged the SCOP-shortened STL. These results revealed that PG,
      PNG GE and CC administered orally for 1 week improved the SCOP-induced learning
      and memory deficit in rats.

PMID- 10925409
TI  - Antiulcerogenic effects of Tylophora conspicua in male rats.
AB  - Studies were undertaken on the effect of a crude (TC) and an alkaloid fraction
      (TA) of the leaf extracts of Tylophora conspicua on indomethacin-induced gastric
      ulceration and gastric acid secretion in male albino rats. Both the TC and TA
      produced a dose-dependent inhibition of gastric ulceration. At a dose level of 40
      mg/kg TC and TA were more effective (TA being more potent) than propranolol in
      inhibiting gastric ulceration. The highest dose of the extracts used (80 mg/kg)
      completely inhibited gastric ulceration. Intravenous administration of the TC and
      TA significantly decreased acid output at low dose (20 mg/kg), medium dose (40
      mg/kg) and high dose (80 mg/kg) from the peak basal of 0.54 +/- 0.02 mEq/L/min to
      0. 49 +/- 0.02 mEq/L/min, 0.35 +/- 0.01 mEq/L/min and 0.21 +/- 0.02 Meq/L/min
      respectively. 80 mg/kg of TC and TA significantly reduced the histamine (1 mg/kg)
      induced gastric acid secretion. The results suggest that the antiulcer activity
      of Tylophora conspicua might be produced by gastric acid inhibition.

PMID- 10925410
TI  - Evaluation of antidiarrhoeal profile of Jussiaea suffruticosa linn. extract in
      rats.
AB  - The antidiarrhoeal potential of a methanol extract of the aerial parts of
      Jussiaea suffruticosa Linn. (MEJS) was studied with several experimental models
      of diarrhoea in rats. MEJS treated rats showed significant inhibitory activity
      against castor oil induced diarrhoea and PGE(2) induced enteropooling. It also
      showed a significant reduction in gastrointestinal motility following a charcoal
      meal in rats. The extract exhibited significant antidiarrhoeal potential at doses
      of 100,200 and 300 mg/kg in all the animal models and thus established the
      efficacy of MEJS as a potent antidiarrhoeal agent.

PMID- 10925411
TI  - Effect of Salvia leriifolia leaf extract on morphine dependence in mice.
AB  - The effect of Salvia leriifolia leaf extract on morphine dependence was
      investigated in mice. Dependence was induced using subcutaneous injections of
      morphine daily for 3 days. On day 4, morphine was injected 2 h before the
      intraperitoneal injection of naloxone. The number of episodes of jumping during
      the 30 min after injection of naloxone was considered as the intensity of the
      withdrawal syndrome. The ethanol extract reduced the number of jumping episodes
      dose-dependently. The extract at a dose of 500 mg/kg was as effective as a dose
      of 5 mg/kg of diazepam in reducing the number of jumping episodes. The effect of
      the extract was blocked by aminophylline (20 mg/kg), a non-selective antagonist
      of adenosine receptors. It is concluded that the ethanol extract of S. leriifolia
      leaves could diminish the withdrawal syndrome of morphine.

PMID- 10925413
TI  - Patents alert

PMID- 10925414
TI  - Selected bibliography

PMID- 10925412
TI  - Guava leaf extract and topical haemostasis.
AB  - The effects of guava leaf extract on the bleeding time and the three main
      mechanisms of haemostasis: vasoconstriction, platelet aggregation and blood
      coagulation, were investigated. The water extract of guava leaves did not shorten
      bleeding times in rats. Guava leaf extract potentiated the vascular muscle
      contraction induced in rabbits by phenylephrine, and when given alone it
      stimulated human platelet aggregation in vitro in a dose-dependent manner. On the
      other hand, it significantly prolonged blood coagulation; activated partial
      thromboplastin time (APTT) test (p < 0.05). The higher the concentration of the
      extract, the longer APTT was observed. Thus, a water extract of guava leaves
      showed ambiguous effects on the haemostatic system. Guava leaf extract did not
      affect bleeding times, it stimulated vasoconstriction and platelet aggregation
      but it inhibited blood coagulation. Therefore, guava leaf extract is not
      recommended as a haemostatic agent.

PMID- 10925415
TI  - Erratum. H.M. Shaheen, B.H. Ali, A.A. Alqarawi and A.K. Bashir. 'Effect Of
      psidium guajava leaves on some aspects of the central nervous system in mice'.
      Phytotherapy research 14(2) 2000, 107-111
AB  - The original article to which this Erratum refers was published in Phytotherapy
      Research 14(2) 2000, 107-111. Following publication of this paper in the March
      2000 issue of Phytotherapy Research (14(2), 107-111), it has come to our
      attention that Figure 3 was printed incorrectly. The correct Figure 3 appears
      below. The publishers would like to apologise for any confusion caused.

PMID- 10925416
TI  - Lateral canthal surgery.

PMID- 10925417
TI  - The lateral transorbital canthopexy for correction and prevention of ectropion:
      report of a procedure, grading system, and outcome study.
AB  - BACKGROUND: There are numerous approaches to correcting laxity of the lateral
      canthal tendon, each with advantages and drawbacks. Critical evaluation of these
      techniques is not possible, however, as there is no grading system currently in
      use to describe this condition or to report outcomes, and prospective trials are
      lacking. OBJECTIVES: To report and assess a new procedure for repair of the
      lateral canthus (lateral transorbital canthopexy) and to describe the Ectropion
      Grading Scale (EGS), with a prospective outcome analysis of their use. DESIGN:
      Prospective outcome study of 15 consecutive patients (16 procedures). SETTING:
      Tertiary referral center in Zurich, Switzerland. PATIENTS: Consecutive sample of
      patients referred for treatment of ectropion of various causes. INTERVENTIONS:
      Preoperative and postoperative EGS grades were recorded, a preoperative and
      postoperative patient-based questionnaire was administered, and lateral
      transorbital canthopexy was performed. MAIN OUTCOME MEASURES: Outcome was
      determined by improvement in EGS grade and results of the patient-based symptom
      questionnaire. RESULTS: There were no surgical failures or complications in the
      study. An average of 83% reduction in patient-reported discomfort was achieved.
      Two patients with facial paralysis needed medial canthal repositioning. The EGS
      allowed clear recording of lower eyelid position before and after lateral
      transorbital canthopexy, and the procedure was uncomplicated to perform.
      CONCLUSIONS: Lateral transorbital canthopexy is an effective technique for the
      correction of lower eyelid laxity and appears to allow refined, durable
      adjustment of the lateral canthus. Self-reported patient satisfaction confirmed
      the high rate of success of the procedure in this study. The EGS permits critical
      evaluation and reporting of results and may assist in predicting which patients
      will need concomitant correction of the medial canthus. Arch Facial Plast Surg.
      2000;2:9-15

PMID- 10925418
TI  - Transconjunctival sub-orbicularis oculi fat (SOOF) pad lift blepharoplasty: a new
      technique for the effacement of nasojugal deformity.

PMID- 10925419
TI  - Lower blepharoplasty is not about removing skin and fat.

PMID- 10925420
TI  - Decreased splatter in dermabrasion.
AB  - OBJECTIVE: To compare a new dermabrasion instrument equipped with a metal shield
      and hydration-suction apparatus with the standard instrument, with specific
      attention to the exposure of operating room personnel to potentially hazardous
      particles. DESIGN: A surgical trial with each of the instruments was performed
      with a skin model. The splatter caused by the 2 instruments was evaluated and
      compared statistically and graphically. SUBJECTS: Female hairless guinea pigs
      (450 g) were used as a skin model. INTERVENTIONS: Ten guinea pigs were treated
      with the standard dermabrading instrument, and 10 were treated with a shielded
      suction-irrigating dermabrader. The splatter was analyzed by counting the number
      of particles landing on strategically placed glass slides. Evaluations of
      histologic cross-sections of the dermabraded skin were compared in a blinded
      fashion. RESULTS: Statistical and graphic analysis showed the number of
      potentially hazardous particles generated by the suction dermabrader to be
      significantly less than that generated by the standard dermabrader. Histologic
      sections showed no difference between the 2 subsets. CONCLUSION: The new shielded
      suction-irrigating dermabrader provides comparable surgical results while
      significantly decreasing exposure to potentially hazardous splatter particles.
      Arch Facial Plast Surg. 2000;2:23-26

PMID- 10925421
TI  - Modulation of tissue ingrowth into porous high-density polyethylene implants with
      basic fibroblast growth factor and autologous blood clot.
AB  - OBJECTIVE: To investigate the effect of direct application of biologic materials
      normally present in wounds (basic fibroblast growth factor [bFGF] and autologous
      blood clot [ABC]) to accelerate the bony and soft tissue ingrowth into porous
      high-density polyethylene implants. METHODS: We conducted a prospective, blinded
      animal histological study. Disks made of porous high-density polyethylene
      impregnated with bFGF or ABC were implanted into adult Sprague-Dawley rats in
      both subcutaneous and subperiosteal locations. Animals were killed and implants
      were harvested at 2, 4, and 10 weeks postimplantation and examined histologically
      for fibroblast invasion, collagen deposition, and inflammatory reaction.The
      results were compared with control (untreated) implants. RESULTS: As a group, the
      histological results showed significantly more fibroblasts within the ABC-treated
      implants than control implants or bFGF-treated implants. This difference in the
      number of fibroblasts between ABC-treated implants and bFGF-treated and control
      implants was also statistically significant 2 weeks after implantation.
      CONCLUSIONS: At the concentration of bFGF of 1 microg/10 microL, no acceleration
      of tissue ingrowth into porous high-density polyethylene implants was noted.
      However, when porous high-density polyethylene implants were treated with ABC,
      the implants were invaded to a greater degree by soft tissue, particularly in the
      early postoperative period (first 2 weeks). Bioactive substances associated with
      the coagulation and platelet cascades present in the ABC may be responsible for
      this accelerated incorporation of the porous implant and may have clinical
      implications. Arch Facial Plast Surg. 2000;2:27-33

PMID- 10925422
TI  - Suture contouring of the nasal tip.
AB  - Scoring, morselizing, and resecting the alar cartilages in an attempt to modify
      the position and shape of the nasal tip may lead to postoperative distortions of
      the lobule. Contour grafts have the disadvantage of asymmetries, visible
      irregularities, and absorption. For these reasons, surgeons have adopted suture
      techniques as the primary method of recontouring the alar cartilages. My
      philosophy in dealing with mild to moderate tip deformities consists of the
      following principles: (1) limited or no resection of cartilages; (2) no scoring
      or morselization of alar cartilages, which produces irreversible change and
      unpredictable results; (3) use of support grafts in the form of columellar struts
      and lateral crural battens to supplement structure and correct intrinsic alar
      cartilage weaknesses; (4) reliance primarily on the use of sutures to recontour
      and position the tip; and (5) limited use of contour grafts for situations that
      cannot be corrected with sutures and support grafts. Arch Facial Plast Surg.
      2000;2:34-42

PMID- 10925423
TI  - Modified Z-epicanthoplasty in the Asian eyelid.
AB  - OBJECTIVE: To propose a new technique for eliminating the medial epicanthal fold
      of the Asian upper eyelid. DESIGN: A retrospective review of the Z
      epicanthoplasty and modified Z-epicanthoplasty procedures performed during 1995
      through 1999. SETTING: Facial plastic surgery private practice. PATIENTS: Four
      hundred seventy-five Korean American patients from 9 midwestern states with type
      2 or type 3 medial epicanthal folds. CONCLUSIONS: The majority of the East Asian
      population has type 2 or 3 medial epicanthal folds. Most surgeons avoid
      epicanthoplasty because of the fear of visible scar formation. Modified Z
      epicanthoplasty is a safe and effective technique for eliminating the epicanthal
      fold during double-eyelid operations. Scarring of the medial canthal area has not
      been a problem with this technique. Arch Facial Plast Surg. 2000;2:43-47

PMID- 10925424
TI  - Autologous collagen dispersion (Autologen) as a dermal filler: clinical
      observations and histologic findings.
AB  - OBJECTIVE: To assess the histologic behavior and clinical efficacy of autologous
      collagen dispersion (Autologen) in augmenting human dermis. SUBJECTS: Adult
      patients of the Facial Plastic Surgery Clinic at The New York Eye and Ear
      Infirmary who were undergoing facial aesthetic surgery with skin excision.
      METHODS: Five patients were injected intradermally with Autologen in one
      postauricular area and bovine cross-linked collagen (Zyplast) on the
      contralateral side. Patients were examined clinically for signs of infection,
      skin necrosis, or implant rejection/allergy 2, 4, and 12 weeks postinjection.
      Impressions and photographs of all implant sites were taken at all follow-up
      visits. Biopsy specimens of each implant were taken 4 and 12 weeks after
      injection and examined histologically for signs of integration, rejection, and
      resorption. RESULTS: All implants were well tolerated. No identifiable
      differences were noted in the clinical persistence of Zyplast vs Autologen.
      Histologically, there was more variability in the degree of fibroblast
      infiltration of Autologen vs Zyplast deposits. CONCLUSIONS: Our trial suggests
      that autologous collagen dispersion may represent a viable alternative to bovine
      collagen. Clinical persistence and histologic behavior of Autologen appear to be
      at least as favorable as those of Zyplast, and Autologen obviates the need for
      allergy testing and eliminates the possibility of disease transmission. Arch
      Facial Plast Surg. 2000;2:48-52

PMID- 10925425
TI  - Reconstruction of total lower lip and chin defects using the composite radial
      forearm--palmaris longus tendon free flap.
AB  - BACKGROUND: Functional and aesthetic restoration of total lip and chin defects
      can be achieved using the composite radial forearm-palmaris longus tendon free
      flap. OBJECTIVE: To present the technique we use and our experience with this
      form of reconstruction in 10 consecutive patients with total lip and chin defects
      who were surgically treated between 1992 and 1998. METHODS: The palmaris longus
      tendon acting as a sling over which the flap is draped is responsible for long
      term maintenance of vertical lip height and lip support. The factors responsible
      for this are the long-term maintenance of vertical lip height and lip support and
      the transfer of facial muscle activity to the neolip. RESULTS: All patients were
      satisfied with their final reconstructive result. Oral competence for deglutition
      and speech was achieved in all patients in our case series, with no incidence of
      drooling. CONCLUSION: We recommend the use of the composite radial forearm
      palmaris longus tendon free flap for this type of reconstructive surgery. Arch
      Facial Plast Surg. 2000;2:53-56

PMID- 10925426
TI  - Aesthetic otoplasty with remodeling of the antihelix for the correction of the
      prominent ear: criteria and personal technique.
AB  - A brief account of some important aspects of the embryological formation of the
      external ear is presented. Family and patient motivations to correct the
      aesthetic aspect of the prominent ear caused by the lack of development of the
      antihelix are discussed. The criteria for the selection of the patients and the
      ideal age for the surgical procedure are analyzed. The objectives of otoplasty
      for the correction of this deformity and the personal technique of the author are
      described. Emphasis is placed on the author's original contributions to this
      procedure and the results. The possible postoperative complications are
      discussed. Arch Facial Plast Surg. 2000;2:57-61

PMID- 10925427
TI  - Editor's comment

PMID- 10925428
TI  - The Food and Drug Administration: an agency to protect the patient and the
      physician.

PMID- 10925429
TI  - Bringing a new medical device to market.

PMID- 10925430
TI  - Review of the course titled "Latest advances in cosmetic surgery of the face,"
      given in Newport Beach, Calif, August 1999.

PMID- 10925431
TI  - Perspective: assuring the safety of facial plastic surgery patients.

PMID- 10925432
TI  - Robert Abbe, MD.

PMID- 10925433
TI  - Lady Hamilton as "Nature".

PMID- 10925434
TI  - Microvascular free flap reconstructive options in patients with partial and total
      maxillectomy defects.
AB  - OBJECTIVE: To evaluate and discuss the free flap reconstructive options for
      patients with partial and total maxillectomy defects. DESIGN: Retrospective
      review of cases. SETTING: Two tertiary referral centers. PATIENTS: Fifty-one
      patients had partial or total maxillectomy defects resulting from oncologic
      surgical resection, and 7 had partial maxillectomy defects resulting from trauma.
      Inferior or partial maxillectomy defects included 10 anterior arch and hemipalate
      defects and 12 subtotal or total palate defects. Total maxillectomy defects with
      and without orbital exenteration included 36 maxilla defects with hemipalate and
      malar eminence. INTERVENTION: There were 11 fibula, 14 rectus abdominis, 9
      scapular, 10 radial forearm, 5 latissimus dorsi, and 13 combination latissimus
      dorsi and scapular flaps. MAIN OUTCOME MEASURES: Separation of the oral cavity
      from the sinonasal cavities, diet, type of dental restoration, type of orbital
      restoration, speech intelligibility, and complications. RESULTS: Only 1 flap
      failure was reported. There was loss of bone in 2 flaps and loss of the skin
      paddle in 1 flap. All palatal defects were sealed by the separation of the oral
      and sinonasal cavities. Thirty-eight patients were able to eat a regular diet
      while the remaining patients maintained a soft diet. All patients conversed on
      the telephone without difficulty in intelligibility. Eight patients had an
      implant-borne dental prosthetic, and 30 patients had a conventional partial
      prosthetic. Orbit restoration was achieved in 2 patients with an implant-borne
      prosthetic, and 6 patients retained a standard orbit prosthetic. CONCLUSIONS:
      Free flap reconstruction of the maxilla creates reproducible permanent separation
      of the oral and sinonasal cavities in a single-stage procedure. In addition,
      there exists the potential for dental rehabilitation with restoration of
      masticatory and phonatory function. Free flap reconstruction also provides a good
      cosmetic result, which improves patients' outlook and contributes to their
      overall well-being. Reconstructive flaps are designed to fit specific maxillary
      defects and patient needs to provide optimally functional and cosmetic results.

PMID- 10925435
TI  - Hemangiomas in infants and children. An algorithm for intervention.
AB  - Considerable confusion exists with the diagnosis and management of vascular
      birthmarks. For this article we reviewed charts for the diagnosis and recommended
      management of 208 new patients with vascular birthmarks presenting to the Albany
      Medical Center Vascular Malformation Clinic, Albany, NY, over a 26-month period
      from October 1995 through December 1997. Based on our patient population, data
      available, and the current literature, we concluded that an early evaluation and
      an accurate diagnosis in infants with a vascular birthmark are important.
      Furthermore, intervention by way of systemic steroids, laser therapy, or surgical
      debulking is appropriate and safe in a select group of patients presenting with a
      proliferating hemangioma and in patients with an involuting but disfiguring
      hemangioma. Also in this article we present an algorithm to assist the clinician
      with the management of the pediatric patient with a diagnosis of a hemangioma.

PMID- 10925436
TI  - Comparison of the aesthetic facial proportions of southern Chinese and white
      women.
AB  - OBJECTIVE: To compare the aesthetic facial proportions of southern Chinese women
      with published average and ideal values for white women. DESIGN: One hundred
      Chinese women between the ages of 18 and 40 years who had not undergone previous
      facial surgery were chosen at random, and their aesthetic facial proportions were
      measured from 5 x 7-in photographs. Comparisons were made with similar reported
      measurements for the white face, and the surgical relevance of the differences
      observed is discussed. RESULTS: The major facial differences observed in the
      Chinese face were the wider intercanthal distance, the wider nasal base, a
      different profile of the lower face, and differences in the eyelids. The Chinese
      nose was less prominent, the alae were more flared, the nostrils were more
      horizontally oriented, the alar-columellar relationships were different, and the
      nasal tip was less defined. CONCLUSIONS: Although the general principles of
      facial plastic surgery apply to both white and Chinese faces, the aesthetic goals
      are different. The aim is to retain the ethnicity and natural appearance of the
      face.

PMID- 10925437
TI  - Cost considerations of converting to digital photography.
AB  - OBJECTIVES: To provide the practicing surgeon with data to make an informed
      economic decision regarding conversion from analog to digital photography.
      METHODS: A cost analysis of photography based on 35-mm vs digital platforms (low
      , medium-, and high-cost hardware). RESULTS: Break-even thresholds for the
      investment in a digital platform of low, medium, and high costs were 3674,
      15,789, and 34,000 images, respectively. CONCLUSION: Given the current excellent
      image quality and ongoing refinements in digital photography, a digital
      photography platform may be cost-effective for a busy facial plastic surgery
      practice.

PMID- 10925438
TI  - Reconstruction of the frontal sinus and frontofacial skeleton with hydroxyapatite
      cement.
AB  - OBJECTIVE: To evaluate the efficacy of a newly developed biomaterial,
      hydroxyapatite cement, for use in frontal sinus and anterior craniofacial
      skeletal reconstruction. DESIGN: A nonrandomized patient cohort that was compared
      with historical controls of standard treatment with methyl methacrylate implants.
      SETTING: Craniofacial reconstructive surgery services at 3 referral health care
      centers. Eligible patients had frontal-cranial defects limited to a maximum size
      of 25 cm2. Patients were randomly selected volunteers with preexistent, acute
      traumatic or acute surgically induced defects of the frontal sinus and anterior
      craniofacial skeleton. All patients provided informed consent, and the study was
      approved by the 3 institutional review boards. Forty patients underwent
      reconstruction of defects of the anterior craniofacial region, and 38 of these
      patients were evaluable at 24 months. MAIN OUTCOME MEASURES: Hydroxyapatite
      cement was used to reconstruct full-thickness anterior craniofacial skull
      defects. Standard surgical techniques were used to place all implants. The
      primary outcome measurement was maintenance of implant volume determined at 24
      months by computed tomography and clinical examination. Secondary outcome
      measures included incidence of complications and infections necessitating implant
      removal. RESULTS: Of the 38 evaluable patients, 31 had successful reconstructions
      at the end of the study, for an overall success of 82% for frontal sinus and
      frontofacial region reconstruction. Seven patients underwent explantation, 5 for
      surgical access to the site. Two implants were removed because of infection in
      the wound, for an overall incidence of approximately 5%. Explant biopsy specimens
      confirmed implant osseointegration and vascularization. CONCLUSIONS:
      Hydroxyapatite cement successfully reconstructs full-thickness defects of the
      frontal sinus and frontofacial region at 24 months. Hydroxyapatite cement appears
      to be superior to acrylic implants for frontal-cranial reconstruction and by
      allowing implant osseointegration with improved biocompatibility.

PMID- 10925439
TI  - Evaluation of acellular dermal graft in sheet (AlloDerm) and injectable
      (micronized AlloDerm) forms for soft tissue augmentation. Clinical observations
      and histological analysis.
AB  - OBJECTIVES: To evaluate the histological and clinical properties of (1)
      subdermally implanted acellular dermal graft (AlloDerm) sheets vs intradermal
      bovine collagen and (2) subdermally or intradermally injected micronized AlloDerm
      vs type I bovine collagen cross-linked with glutaraldehyde (Zyplast). PATIENTS:
      Twenty-five adult patients testing nonallergic to bovine collagen. METHODS: (1)
      Stacked disks of AlloDerm were implanted subdermally behind one ear, and bovine
      collagen was injected intradermally behind the other. The soft tissue
      augmentation caused by the implants was measured by digital photography at 1, 4,
      and 12 weeks, and biopsy specimens of each implant type were examined at 3 months
      after implantation. (2) Micronized AlloDerm was injected intradermally and
      subdermally in 2 different locations behind one ear, and bovine collagen was
      injected in the same manner behind the other. The soft tissue augmentation caused
      by the implants was measured by digital photography at the time of implantation
      and at 1 and 4 weeks after implantation. All implants were examined 1 month after
      implantation. RESULTS: All patients tolerated both implants well. (1) AlloDerm
      implants retained a higher percentage of the original implant volume than Zyplast
      at 1 and 3 months after implantation. Histologically, AlloDerm implants were
      extensively invaded by host fibroblasts without any foreign body reaction. (2)
      Intradermally injected micronized AlloDerm implants retained a higher percentage
      of the original implant volume at 1 month after implantation than intradermal
      Zyplast. Histologically, micronized AlloDerm implants were extensively invaded by
      host fibroblasts without any foreign body reaction. No significant differences
      were noted between subdermally injected micronized AlloDerm and Zyplast.
      CONCLUSIONS: The macroscopic and microscopic behavior of subdermally implanted
      AlloDerm sheets and subdermally and intradermally injected micronized AlloDerm
      was compared with intradermally injected Zyplast. AlloDerm sheet volume persisted
      to a significantly (P < .001) greater degree than bovine collagen during the
      first 3 months after placement. Clinically, intradermally injected micronized
      AlloDerm volume persisted to a significantly (P = .01, .04, and .01,
      respectively) greater degree than intradermal Zyplast or subdermal micronized
      AlloDerm or Zyplast. Histologically, micronized AlloDerm and AlloDerm are well
      tolerated at 1 and 3 months, respectively. Host tissue incorporation with
      fibroblast in-growth and collagen deposition is seen in both materials. AlloDerm
      and micronized AlloDerm hold promise for use in facial soft tissue augmentation.

PMID- 10925440
TI  - Carbon dioxide laser abrasion. Is it appropriate for all regions of the face?
AB  - OBJECTIVES: To evaluate the effectiveness of the carbon dioxide laser for
      treatment of facial acne scarring and to determine if certain regions of the face
      would respond more favorably to carbon dioxide laser resurfacing than other areas
      of the face. METHODS: Twenty-five patients with facial acne scarring were treated
      with the carbon dioxide laser with the flash-scanning attachment. Physician and
      patient evaluations were performed at postoperative follow-up. The face was
      evaluated for improvement by 5 anatomic regions: medial and lateral cheeks,
      perioral region, temple, and forehead. SETTING: Office ambulatory surgery center.
      RESULTS: Patients demonstrated overall improvement with the carbon dioxide laser.
      However, certain areas, such as the lateral cheek and temple, responded less
      favorably than other areas, such as the medial cheek, perioral region, and
      forehead. These findings were found to be statistically significant (P < .001)
      for physician and patient assessments. No long-term complications were reported.
      CONCLUSIONS: The carbon dioxide laser is an effective modality for the treatment
      of facial acne scarring. Physician and patient satisfaction is high.
      Nevertheless, multiple treatments may be necessary to achieve improvement,
      especially in the temple and lateral cheek areas; these anatomic sites respond
      less favorably to laser resurfacing than the medial cheek, perioral region, and
      forehead.

PMID- 10925441
TI  - The extended Abbe flap in the reconstruction of complex midfacial defects.
AB  - The Abbe flap is most commonly used to repair full-thickness defects of the lip
      that do not involve the commissure. This well-perfused axial flap is based on the
      labial branches of the facial artery. The inferior labial vessels have been shown
      to support a cutaneous territory, including the entire lower lip, chin, and
      submental skin. Defects extending beyond the confines of the upper lip may be
      reconstructed with an extended lip switch flap that is based on the inferior
      labial artery. This "extended" Abbe flap allows functional and cosmetically
      acceptable repair of the upper lip, medial cheek, columella, and nasal sill. Case
      presentations illustrate the technique and outcome.

PMID- 10925442
TI  - Combined tongue and pharyngeal flaps for reconstruction of large recurrent
      palatal fistulas.

PMID- 10925444
TI  - Irving B. Goldman, MD (1898-1975): Master Rhinoplasty Surgeon.

PMID- 10925443
TI  - Ectopic hair growth after flap reconstruction of the head and neck.

PMID- 10925445
TI  - Eugene Bortnick, MD.

PMID- 10925446
TI  - Continuing Medical Education.

PMID- 10925447
TI  - Portrait of a Man in a Red Cap.

PMID- 10925448
TI  - Reprocessing of endoscopic accessories reusable, disposable, or reposable.

PMID- 10925449
TI  - High prevalence of hepatitis C virus infection in Belgian intravenous drug users
      and potential role of the "cotton-filter" in transmission: the GEMT Study.
AB  - AIMS: To estimate viral seroprevalences for HCV, HBV and HIV among belgian
      intravenous (IVDU) and non intravenous (non-IVDU) drug users; to assess risk
      factors for HCV infection in IVDU; to assess feasibility of chronic hepatitis C
      follow-up in this population. DESIGN: Cross-sectional study. Demographic and
      behavioural characteristics were obtained by a standardized questionnaire. Serum
      samples were tested for HCV, HBV and HIV. SUBJECTS AND SETTING: 329 patients (244
      IVDU and 85 non-IVDU) attending ten general practitioners in 1995. RESULTS: HCV
      seroprevalence was 78.3%; it was 35.7% for HBV and 0.9% for HIV in IVDU, vs 2.4%,
      8.3% and 0%, respectively, in non-IVDU. In logistic regression analysis,
      independent risk factors for HCV infection were: 1/sharing of syringes and/or of
      "cottons" used as filters (adjusted prevalence odds ratio [POR] = 31.7; 95%
      confidence interval [CI] = 9.8-102.5), 2/duration of injecting upper than one
      month (adjusted POR = 8.6; CI = 3.0-24.7) and 3/age (adjusted POR = 1.2 by year
      of difference; CI = 1.0-1.3). A biochemical follow-up was obtained in 70% of HCV
      seropositive users; 79.5% of them had chronic hepatitis C (mean value of ALT =
      3.5 times upper normal value, range 1.1-23.0). Among these, 24.7% went through
      liver biopsy during the three years follow-up period of the study. CONCLUSIONS:
      HCV seroprevalence is very high among belgian IVDU. Prevention strategies have to
      focus on neophytes injectors. They must be urgently revisited for what concern
      needles/syringes exchange programs: "cottons" must be included. Follow-up and
      treatment of chronic hepatitis C seem to be poorly effective among drug users.

PMID- 10925450
TI  - Evaluation of the role of human papillomavirus in oesophageal squamous cell
      carcinoma in Belgium.
AB  - OBJECTIVE: To evaluate the putative role of human papillomavirus (HPV) in the
      aetiology of oesophageal squamous cell carcinoma (OSCC) in Belgium. METHODS: The
      frequency of HPV infection was determined using HPV DNA PCRamplification with L1
      consensus primers MY09-MY11, able to recognise about 40 different HPV types, on
      twenty-one formalin-fixed and paraffin-embedded oesophageal squamous cells
      carcinomas. Nineteen samples of histologically normal epithelium from the
      surgical margins of the OSCC specimens and five samples from normal oesophagus
      obtained at autopsy served as negative controls. RESULTS: We found only one HPV
      positive tumour (4.8%) out of the 21 OSCC cases. All the normal epithelium
      controls remained negative. CONCLUSIONS: Our data are in agreement with those
      previously published, suggesting that HPV infection only plays a minor role in
      the pathogenesis of oesophageal squamous cells carcinoma in West-European
      countries.

PMID- 10925451
TI  - The coeliac iceberg: a consensus in paediatrics.

PMID- 10925452
TI  - Percutaneous treatment of liver metastases.

PMID- 10925453
TI  - Stenting of upper and lower GI tract obstruction.

PMID- 10925454
TI  - Hepatic chemoembolization: clinical and experimental correlation.
AB  - Chemoembolization has become the preferred treatment for patients with
      inoperable, hypervascular hepatic malignancies in the Far East, but controversial
      elsewhere. In vivo microscopy in addition to other experimental procedures are
      used in this presentation to better understand the mechanisms involved in
      chemoembolization. In chemoembolization Lipiodol acts as a contrast material, a
      vehicle for chemotherapy and an embolic agent. Although not optimal, Lipiodol
      injected into the hepatic artery, traverses the peribiliary plexus to the portal
      veins resulting in a dual embolization. Chemoembolization creates ischemia, slows
      arterial flow and increases the contact time between the infusate and the
      neoplasms, increasing the tumor cell kill. However, the vascular occlusion also
      produces infarction and fibrosis compounding the already existing cirrhosis
      frequently associated with hepatocellular carcinoma. Lipiodol/ethanol (3:1)
      injected into the segmental or lobar hepatic artery supplying the neoplasm also
      gains access to the associated portal venous branches causing focal ablation.
      This preoperative approach is easier to perform than direct portal vein
      occlusion, with less parenchymal damage and comparable hypertrophy of the remnant
      liver frequently necessary for adequate hepatic function following resection.
      Polymer-drug conjugates, e.g. PG-TXL, have considerable potential for intra
      arterial delivery especially with the dramatic increase in concentration of the
      drug in the tumor and its efficacy. Using in vivo microscopy especially with
      green fluorescent protein (GFP) gene as an efficient and non-toxic tumor cell
      marker, the events leading to hepatic metastases can be documented which will
      serve to better evaluate these varied techniques of chemoembolization.

PMID- 10925455
TI  - T.I.P.S.: follow-up imaging and revision procedure.
AB  - TIPS patency can be assessed by different imaging techniques: angiography, color
      Doppler sonography, CT angiography, scintigraphy. Percutaneous angiography with
      measurement of the portocaval pressure gradient is the gold standard in the
      diagnosis of shunt failure, but, because its invasive nature and the necessity of
      frequent control of the shunt function, a noninvasive procedure is preferable for
      routine checkup. Color Doppler sonography in intervals of 3 to 6 months, with the
      use of different criteria, is considered as an accurate imaging technique with a
      high degree of sensitivity and specificity to evaluate TIPS patency. Angiography
      is indicated when CDS is not successful or in each clinical recurrence. Revision
      procedure may restore shunt efficiency and is indicated when the TIPS patency is
      compromised.

PMID- 10925456
TI  - Hepatitis B virus receptor: the role of human annexin V.

PMID- 10925457
TI  - S gene variation of HBV.

PMID- 10925458
TI  - An overview on a novel adjuvanted prophylactic hepatitis B vaccine.

PMID- 10925459
TI  - Treatment for chronic hepatitis B: interferon what we have learned after so many
      years?

PMID- 10925460
TI  - Treatment of chronic hepatitis B: lamivudine.

PMID- 10925461
TI  - New nucleoside analogues for chronic hepatitis B.

PMID- 10925462
TI  - Immune therapy of hepatitis B virus (HBV) chronic infection. European experience.

PMID- 10925463
TI  - Hepatitis B virus and liver transplantation.

PMID- 10925464
TI  - Hepatitis C: virology, clinical aspects and the relation to cryoglobulinemia.

PMID- 10925465
TI  - HCV, HDV and autoimmunity.

PMID- 10925466
TI  - Treatment of chronic hepatitis C with interferon in combination with other
      compounds.

PMID- 10925467
TI  - Prognostic factors determining the outcome of treatment in chronic hepatitis C.
AB  - After a brief introduction in terminology and a distinction between predictors
      and determinants or response to therapy in chronic hepatitis C, a review of the
      wide literature on this topic is presented. None of the pretreatment variables or
      combination of them can be used as an absolute predictor of response in
      individual patients. Prognostic factors can help in clinical practice for
      informing and counseling patients of the likelihood of response. Information on
      pretreatment HCV RNA levels and HCV genotype can improve the cost benefit of
      therapy. Predictors of response should be properly evaluated in terms of positive
      predictive value, negative predictive value and accuracy. The strongest hitherto
      predictor of sustained response to any therapeutic regimen in chronic hepatitis
      is the clearance of HCV RNA during treatment. Recent data suggest that sequencing
      of several regions of the HCV genome may provide important prognostic information
      on the outcome of therapy. In complex and difficult to treat subsets of patients
      with chronic HCV infection, available data on predictors and determinants of the
      outcome of treatment are limited.

PMID- 10925468
TI  - Development of novel anti-HCV therapies: HCV protease, helicase, and polymerase
      as therapeutic targets.

PMID- 10925469
TI  - In vitro assays for drug testing: continuous cell lines.

PMID- 10925470
TI  - Infectious synthetic HCV transcripts.

PMID- 10925471
TI  - Hepatitis C virus and transplantation.

PMID- 10925472
TI  - Hepatitis D: virology, clinical and epidemiological aspects.

PMID- 10925473
TI  - New agent to cause acute fulminant hepatitis?

PMID- 10925474
TI  - Epidemiology of hepatocellular carcinoma and its viral risk factors.

PMID- 10925475
TI  - HCV-infection and hepatocellular carcinoma.

PMID- 10925476
TI  - Non-surgical treatment of hepatocellular carcinoma (HCC).

PMID- 10925477
TI  - Perforated gastric ulcer complicating corticosteroid therapy in acute rheumatic
      fever.
AB  - We report an 11-year-old boy with acute rheumatic fever who presented with
      gastric perforation while treated with corticosteroids (CS). He had been treated
      initially with acetylsalicylic acid for 11 days, CS replaced the treatment with
      acetylsalicylic acid due to deterioration of carditis. The possible pathogenesis
      is discussed.

PMID- 10925478
TI  - Lymphangioma of the colon: a case report and review of the Japanese literature.
AB  - Intraabdominal lymphangiomas are rare, although these lesions can occur in the
      mesentery, omentum, retroperitoneum, or gastrointestinal tract wall. Here we
      report a case of lymphangioma of the transverse colon and review the other cases
      reported in the Japanese literature. Our patient presented with lower abdominal
      pain and barium enema revealed a filling defect in the transverse colon.
      Colonoscopy disclosed a submucosal tumor, which changed shape with alteration the
      patient's position and showed the cushion sign. This lesion was covered with
      normal-looking mucosa. A correct diagnosis was made from these findings.
      Knowledge of these endoscopic features may help physicians to provide appropriate
      diagnosis and treatment of colonic lymphangioma.

PMID- 10925479
TI  - The inferior oilvary complex.
AB  - Although many studies have established the connections of the inferior olivary
      complex, there have been relatively few studies on the morphology of this nuclear
      complex. On the base of the similar topographic relations and connections with
      the cerebellum, the inferior olivary complex is regarded as homologous in all
      vertebrates. We present comprehensive light microscopical qualitative and
      quantitative analysis of the inferior olivary complex in different
      representatives of submammilian and mammilian vertebrates, including human. A
      detailed comparison was made at the structural level. Cytoarchitecture and
      cellular morphology of the inferior olivary complex have been studied in several
      submammilian (carp, frog, lizard, tortoise, pigeon) and mammilian species (rat,
      cat, and for the first time ground squirrel Citellus citellus L), including
      human.

PMID- 10925480
TI  - [The future of surgical cellular biology].

PMID- 10925481
TI  - [Management of pain in pancreatic cancer].
AB  - Pain remains an indicator of progression of cancer of the pancreas. Regular pain
      evaluation combined with early analgesic treatment improves the duration and
      quality of life. New modes of morphine administration and specific chemotherapy
      can improve this management. Neurolysis is more effective in the case of recent
      pain, previously controlled by anti-inflammatory drugs. The endoscopic ultrasound
      (EUS)-guided technique allows celiac block during EUS examination for local
      staging. Early introduction of palliative surgery and analgesic procedures can
      reduce the morbidity and mortality of these procedures. A graduated
      multidisciplinary pain management program allows optimal pain control.

PMID- 10925482
TI  - [Perineal gangrene: new bacteriologic approach. Results of medico-surgical
      treatment (81 cases)].
AB  - STUDY OBJECTIVE: The objective of this retrospective study was to report the
      results of a series of 81 cases of perineal gangrene treated in the same center.
      PATIENTS AND METHODS: From 1988 to 1998, 81 patients (64 males, 17 females, mean
      age: 58 years) with perineal gangrene were treated by a medico-surgical team, by
      means of a protocol combining appropriate intensive care measures based on a new
      bacteriologic concept of infectious agents, extensive excisions and drainage of
      the infraperitoneal region and hyperbaric oxygen therapy. RESULTS: The mortality
      rate was 24.7%. Mean duration of intensive care stay was 19 days, mean duration
      of hospital stay was 31 +/- 4 days (range: 6 to 60 days). Risk factors were: age
      > 68 years (p = 0.001), shock (p = 0.83), subcutaneous crepitation (p = 0.25) and
      severity index > 10 (p = 0.003). Sequelae were anal incontinence (n = 3) and
      permanent colostomy (n = 5). Secondary plastic reconstruction was necessary in
      four patients. There were no urologic or genital sequelae. CONCLUSION: Perineal
      gangrene is still a very serious disease. The time to treatment, the simplified
      severity index and consideration of bacteriologic combinations are the main
      prognostic factors.

PMID- 10925483
TI  - [Nuclear magnetic resonance cholangiography in biliary disease. Prospective study
      in 60 patients].
AB  - PURPOSE: The aim of this prospective study was to evaluate a new MR
      cholangiography sequence, with thick slices, single shot fast spin echo (SSFSE)
      in biliary obstructive diseases. PATIENTS AND METHODS: This study included 60
      patients (36 males and 24 females, mean age: 69 years) with cholestatic syndrome
      and suspected bile duct obstruction. All patients were prospectively investigated
      with MR cholangiography using SSFSE sequence with thick slices. The gold standard
      was ERCP (n = 47), per cutaneous cholangiography (n = 1), and surgical
      intervention (n = 12). According to this gold standard, 22 patients had
      obstructive gallstones, 23 had neoplastic obstruction, eight had inflammatory or
      postoperative stenosis and 7 had normal bile ducts. RESULTS: The sensitivity and
      specificity of MR cholangiography were 100 and 94% in the diagnosis of
      obstructive gallstones, and 95 and 97% in the diagnosis of neoplastic
      obstruction, respectively. A good agreement was observed between MR
      cholangiography and the gold standard, regardless of the site of obstruction
      (range of kappa value: 0.79-1). CONCLUSION: MR cholangiography with SSFSE
      sequence is an effective and easy technique. Acquisition of thick slices in a
      very short time (< 2 sec) limits cardiorespiratory artefacts and eliminates the
      need for post-processing.

PMID- 10925484
TI  - [Hepatic portal venous gas].
AB  - STUDY OBJECTIVE: Hepatic portal venous gas is a radiological symptom associated
      with a poor prognosis (75% to 90% mortality). The aim of this retrospective study
      was to report 7 cases observed over a 2-year period. PATIENTS AND METHOD: From
      June 1997 to November 1999, hepatic portal venous gas was diagnosed in 6 patients
      by CT scan and in one patient by echosonography. It was not detected in any case
      by plain abdominal X-rays. Three patients had small bowel obstruction with
      necrosis, three had extensive superior mesenteric infarction and one had
      preperforative necrosis of the colon. RESULTS: One patient with extensive
      intestinal infarction and a metastatic head and neck cancer was not operated. Two
      patients were operated, but the extensive mesenteric infarction was not amenable
      to surgical management. Three of the 7 patients died, while the other four
      patients survived after resection of the necrotic small intestine (n = 3) and
      left colectomy extended to the transverse colon (n = 1). CONCLUSION: Hepatic
      portal venous gas was associated with intestinal necrosis in the seven cases of
      this series. The severity of portal venous gas is only correlated with the
      severity of the disease causing portal venous gas.

PMID- 10925485
TI  - [Hand-sewn intra-abdominal anastomosis performed via video laparoscopy during
      colorectal surgery].
AB  - STUDY OBJECTIVE: Laparoscopic colectomies have been recently shown to be feasible
      and safe, with the use of stapling devices to fashion the anastomosis. The aim of
      this study was to evaluate the feasibility and safety of laparoscopic intra
      abdominal hand-sewn anastomosis. PATIENTS AND METHODS: Seven patients (four males
      and three females, mean age 48 years) were included. There were two ileocolic
      resections for recurrence of Crohn's disease, two right colectomies (one for
      Crohn's disease and one for carcinoid tumor of the appendix), two left
      colectomies for diverticulitis and one segmental colectomy for sigmoid volvulus.
      There were: four side-to-side anastomoses, two side-to-end anastomoses and one
      end-to-end anastomosis. Anastomoses were fashioned with interrupted single layer
      sutures in four cases (two ileo-colic and two colorectal anastomoses) and with
      single layer running sutures in three cases (two ileo-colic and one colo-colic
      anastomoses). The specimens were retrieved by means of a plastic bag through a 3
      to 5 cm long minilaparotomy in five cases and through the rectum in two cases.
      RESULTS: Mean additional time to perform hand-sewn intra-corporeal anastomosis
      was 90 +/- 15 min. There was no operative mortality and no intraoperative
      complications. Postoperative course was uneventful in six patients. Patients were
      started on an oral fluid diet on day 2 and discharged on day 5, except for one
      patient with Crohn's disease who had a severe anastomotic bleeding on
      postoperative day 2 and who required laparotomy for hemostasis through a service
      colotomy with a single suture. He was discharged on day 8. CONCLUSION: Intra
      abdominal hand-sewn anastomoses are feasible and seem reliable. This represents a
      new step making laparoscopic procedures even closer to conventional techniques.
      This technique must be evaluated in larger series.

PMID- 10925486
TI  - [Conization with positive margins: what strategy should be adopted?].
AB  - OBJECTIVE: To define recommended treatment in cases of positive margins on cone
      biopsy specimens. PATIENTS AND METHODS: This single-center retrospective study
      concerned 220 conizations performed between January 1996 and June 1998. The
      results of 70 conizations (31.8%) with positive margins were analysed. There were
      32 cold knife conizations (mean age: 43 years) and 38 conizations by the loop
      electrosurgical excision procedure (mean age: 33 years). RESULTS: Mean depth of
      conization was 15.94 mm for cold knife conization and 10.08 mm for loop
      electrosurgical conization. Fifteen patients were excluded (5 with invasive
      cancer and 10 were lost to follow-up). This study included 55 patients with a
      mean 12-month follow-up. Six underwent hysterectomy for mini-invasion on the
      specimen or advanced age. Eleven underwent a second conization (followed by
      hysterectomy in 2 cases). The other 38 patients were submitted to simple
      surveillance with cervico-vaginal cytology and colposcopic examination. The rate
      of residual lesions (cervical intra-epithelial neoplasia: CIN 3) after conization
      with positive margin was 14.5% (n = 8). CONCLUSION: Residual persistent dysplasia
      is not present in all patients after conization with positive margins. Cytology
      and colposcopy allow detection of dysplasia, indicating the need for a second
      conization. In women with no desire for further pregnancy, systematic repeat
      surgery must be recommended.

PMID- 10925487
TI  - [Inframalleolar bypass in limb salvage. Late results].
AB  - STUDY OBJECTIVE: The objective of this retrospective study was to report the long
      term results of distal revascularization at the ankle in patients with critical
      ischemia. PATIENTS AND METHODS: From January 1989 to November 1999, 50
      inframalleolar bypasses were performed in 49 patients (35 males and 14 females
      with a mean age of 75 years [range: 51 to 95 years]). Twenty-five patients (50%)
      were diabetics. All patients presented with critical ischemia of the lower limb.
      Distal anastomosis was performed at the retromalleolar posterior tibial artery in
      28 cases (56%), pedal artery in 20 cases (40%) and distal fibular artery in two
      cases (4%). Bypasses were performed using a greater saphenous vein (n = 38), a
      cryopreserved arterial allograft (n = 9), or a PTFE graft (n = 2). A composite
      graft with greater saphenous vein and arterial allograft was performed in two
      cases. RESULTS: There were two early postoperative deaths. One patient presented
      a blow-out of the distal anastomosis that required bypass ligation and subsequent
      leg amputation. Early thrombosis of the graft occurred in four cases, leading to
      major amputation in three cases. No patients were lost to follow-up and mean
      follow-up was 26.7 months (range: 1 to 86 months). Graft thrombosis occurred in
      15 patients and led to amputation in 6 cases. Bypass graft patency rate was 72%
      and 61% at 1 year and 3 years, respectively, yielding a 80% limb salvage rate at
      3 years. The 3-year actuarial survival rate was 53%. CONCLUSION: Inframalleolar
      bypasses are a valuable tool in patients with critical ischemia. The lower limb
      salvage rate is satisfactory in this elderly population. Based on this
      experience, angiography with good run-off and, when necessary, a surgical
      approach to verify patency of the arteries at the ankle should always be
      performed before undertaking a major amputation.

PMID- 10925488
TI  - [Treatment of parathyroid adenomas with ethanol injection under ultrasonographic
      guidance].
AB  - STUDY OBJECTIVE: The objective of this retrospective study was to report the
      results of ethanol injection in parathyroid adenomas. PATIENTS AND METHOD: Since
      1988, 31 patients with inoperable primary hyperthyroidism have been treated by
      ultrasound-guided percutaneous ethanol injection into the adenoma. The main
      surgical contraindications were heart failure (n = 12) and age over 85 years (n =
      11). Plasma calcium and PTH were measured 48 hours after ethanol injection and
      during subsequent follow-up. RESULTS: Patients had one to three ethanol
      injections. With a mean 5-year follow-up, total success with normal plasma
      calcium and PTH levels was achieved in 20 patients (64.5%), 4 of whom underwent
      another ethanol injection after 1 to 3 years. Partial success with correction of
      plasma calcium only was achieved in 9 patients (29%) resulting in an obvious
      clinical benefit. Failure was observed in 2 patients (6.5%) with nodular goiter,
      probably due to incorrect localization of the adenoma. Treatment was always well
      tolerated and no major side effect was observed. CONCLUSION: Ultrasound-guided
      percutaneous ethanol injection of parathyroid adenoma is effective in most cases
      of hyperparathyroidism and very useful in patients with a high surgical risk. The
      need for precise ultrasound localization of the adenoma is the main limitation of
      this treatment.

PMID- 10925489
TI  - [Chemotherapy by isolated liver perfusion with endovascular occlusion catheter:
      preliminary experience in pigs].
AB  - Very high concentrations of cytotoxic drug may be obtained with chemotherapy
      performed with vascular exclusion. OBJECTIVE: To study the pharmacokinetics and
      toxicity of melphalan during in situ isolated liver perfusion, and to test an
      endovascular occlusion catheter. METHODS: Isolated liver perfusion with melphalan
      (15 mg bolus) was performed in 6 pigs (50-60 kg) for 30 min, with non-oxygenated
      Ringer's solution. Hepatic outflow, collected by a double balloon catheter
      inserted into the retrohepatic inferior vena cava, was pumped into the
      gastroduodenal artery, while the common hepatic artery and portal vein were
      clamped. RESULTS: A maximum concentration of 30,000 ng/mL was obtained in the
      circuit before an exponential decrease, while the concentration in systemic blood
      was less than 500 ng/mL (n = 3). Before closing the abdomen, melphalan
      concentrations were about 2,000 ng/mg in the liver, and undetectable in the
      muscle. Postoperative course (2 weeks, n = 2) was uneventful with minor
      alterations in blood tests and hepatic histology. CONCLUSION: This method of
      local chemotherapy with melphalan appears to be safe with minor leakage and
      minimal toxicity.

PMID- 10925490
TI  - [Evaluation of the Ultracision ultrasonic dissector in thyroid surgery.
      Prospective randomized study].
AB  - STUDY OBJECTIVE: This prospective randomized study was designed to evaluate the
      efficacy, safety and cost of the ultrasonic hook in thyroid surgery, in
      comparison with conventional hemostasis. METHODS: Thirty-four consecutive
      euthyroid patients with multinodular goiter undergoing total thyroidectomy were
      randomly assigned to either group I, Ultracision or group II, conventional
      hemostasis. Preoperative, intraoperative and postoperative biochemical, clinical,
      surgical and economic variables were compared in each group. RESULTS: Use of the
      ultrasonic hook resulted in a significant reduction in operating time (70.7 +/-
      18.3 versus 96.5 +/- 28.9 minutes), blood loss (74.5 +/- 50.9 g versus 134.6 +/-
      108.42 g), and postoperative analgesic consumption (paracetamol (mg): 700 +/- 722
      versus 1888 +/- 978), and may also reduce the incidence of transient
      hypoparathyroidism (5.8% versus 23.5%). The ultrasonic hook was no more expensive
      than conventional hemostasis, as long as a minimum of 15 patients shared the
      initial unit cost of the device. CONCLUSION: Although the use of the ultrasonic
      dissector does not allow a major cost-saving in total thyroidectomy, the
      essential advantages were a significant reduction of intraoperative blood loss,
      length of operating time and postoperative analgesic consumption.

PMID- 10925491
TI  - [Atypical metastatic sites in rectal cancer].
AB  - We report the case of a 48-year-old woman operated on for rectal carcinoma and
      subsequently for metastasis located in three unusual sites (i.e., laryngeal,
      muscular and cutaneous). Three months after the last surgery, the patient was
      still alive, without any detectable metastasis.

PMID- 10925492
TI  - [Portal vein aneurysm].
AB  - In a 72-year-old female patient suffering from non specific and vague abdominal
      pain, an aneurysm of the portal vein was discovered. In the absence of
      complication, and because the risk of operation appeared too high, the decision
      was to abstain from surgery. With more than 3 years of regular follow-up, the
      patient was free of symptoms, and the portal vein aneurysm was unchanged. Sixty
      cases including this one are reviewed.

PMID- 10925493
TI  - [Organization of surgery in Germany].

PMID- 10925494
TI  - [Gaspard II Bartholin and the vulvovaginal gland].
AB  - Born in 1655 in Copenhagen to a renowned family, Gaspard Bartholin had the good
      fortune during his stay in Paris to meet Joseph Guichard du Verney, a French
      anatomist who had discovered the glandula vestibuloris major. Back in Copenhagen
      he was appointed professor of anatomy at the age of 21 described the physiology
      of the glandula vestibuloris major, later known as Batholin's gland. Ennobled,
      laden with honours, he was later appointed personal physician to the king of
      Denmark until his death in 1738.

PMID- 10925495
TI  - [Stomal recurrence of rectal adenocarcinoma. Resection-transposition of colostomy
      without laparotomy].

PMID- 10925496
TI  - [Segmental idiopathic infarction of the greater omentum: a case report].

PMID- 10925497
TI  - [Duodenojejunal Crohn's disease. Contribution of Jordan's method: report of a
      case].

PMID- 10925498
TI  - [Rupture of a hydatic cyst of the diaphragm in the pleura: a case report].

PMID- 10925499
TI  - [Solitary bulky biliary cyst in an infant treated by laparoscopy].

PMID- 10925500
TI  - [A right abdominodiaphragmatic wound by zebu goring].

PMID- 10925501
TI  - Preventive dentistry for the general dental practitioner.
AB  - Although the prevalence of dental caries has decreased gradually in the past
      three decades in the Australian population, dental caries remains the primary
      reason for tooth loss in Australia. At the community level, total health
      expenditure on the treatment of dental caries (and its consequences) is
      substantial. Accordingly, caries prevention is an important focus at both the
      individual and community levels. This paper outlines the principles upon which
      modern caries prevention is based and stresses the importance of manipulating the
      oral environment (in terms of salivary parameters, ions, pH and the oral flora)
      as a major strategy for effective long-term caries prevention. Practical advice
      is provided on the correct home use of preventive agents, including chewing gums,
      chlorhexidine, fluorides, bicarbonate rinses and phosphopeptides.

PMID- 10925502
TI  - Localised enamel hypoplasia of human deciduous canines: genotype or environment?
AB  - A discrete area of defective enamel formation that appears on the labial surface
      of the crowns of deciduous canine teeth has been described in both recent and
      prehistoric human populations, with reported frequencies varying from 1 to 45 per
      cent. Suggestions about the aetiology of this localized hypoplasia range from
      genotypic factors to environmental conditions and systemic effects. The major
      aims of this study were to describe the frequency of occurrence and pattern of
      expression of the lesion in Australian Aboriginal and Caucasian ethnic groups,
      and to clarify the role of genetic factors by examining a sample of twins. The
      study sample consisted of dental casts of 181 pairs of Australian Caucasian
      twins, 215 Aborigines and 122 Caucasian singletons, together with 253 extracted
      deciduous canines. Examination of dental casts and extracted teeth was undertaken
      under 2x magnification with emphasis being placed upon location and expression of
      the lesion. The defect was observed in 49 per cent of twins and 44 per cent of
      Aborigines, but only 36 per cent of singletons. The percentages of affected teeth
      in each group were: 18 per cent in twins, 17 per cent in Aborigines and 13 per
      cent in Caucasians. A significant proportion of the defects occurred on the
      mesial aspect of the labial surface, in the middle area incisocervically, with
      the majority in the lower jaw. A number of significant differences in frequency
      were observed between groups, sexes, arches and sides. The results confirm some
      of the findings of previous studies, but also suggest that none of environmental,
      genetic or systemic factors can be ruled out as being involved in aetiology of
      the defect. The higher incidence of the lesion occurring on the mesial aspect of
      the labial surface is suggestive of physical trauma. Also, the vulnerability of
      the prominent developing mandibular canine, with its thin or missing labial
      covering of bone, would be expected to lead to higher prevalence of the lesion in
      the lower jaw. Although not definitive, the results of concordance analyses in
      twins were suggestive of a possible genetic predisposition in the formation of
      the lesion. Further research with a greater clinical orientation and emphasis on
      determining specific aetiological factors within any given environment in
      different ethnic groups may provide better insight into the ambiguous aetiology
      of the hypoplastic enamel defect.

PMID- 10925503
TI  - Restoring the vertical dimension of mandibular incisors with bonded ceramic
      restorations.
AB  - Mandibular incisors are difficult to restore with conventional anterior crowns
      due to their small axial diameters. Crown preparation risks pulp exposure and
      results in a thin core of dentine. An experiment was designed to determine if
      increasing the thickness of ceramic to restore incisal edges affects the load at
      the point of restoration failure. Forty-eight mandibular incisors were randomly
      divided into four groups. The incisal edges of the teeth in three groups were
      reduced so that the coronal height was 7.5 mm (Group A), 6.5 mm (Group B), and
      5.5 mm (Group C). Group D was designated as the experimental control. A fifth
      group (Group E), independent of the random sample, was introduced to the study
      for discussion purposes and was characterized by each of the incisors having an
      intact incisal edge of enamel. Groups A, B and C were prepared in a standard
      fashion for ceramic veneer restorations that were constructed to restore the
      vertical height of each tooth to 8.5 mm. Prior to cementation, the preparation
      surfaces were analysed and the relative surface areas of enamel and dentine were
      calculated. The ceramic restorations were cemented using a resin luting agent.
      The teeth were then thermocycled prior to loading at 135 degrees C until failure.
      The mean fracture load was 305 N (SD 134 N) for Group A, 403 N (SD 101 N) for
      Group B, 515 N (SD 296 N) for Group C, 587 N (SD 187 N) for Group D and 395 N (SD
      129 N) for Group E. As determined by analysis of variance followed by a Sheffe
      multiple comparison test there was a significant difference (p < or = 0.01)
      between Group A and Group D. There were no significant correlations of load at
      failure with the percentage of exposed dentine, enamel surface area, total
      preparation surface area, and the incisal surface area. The patterns of failure
      of the fractured specimens were also analysed. There were significantly (p < or =
      0.05) greater fractures of the ceramic restorations when they were bonded with
      the minimum incisal thickness of ceramic.

PMID- 10925504
TI  - Studies of dental root surface caries. 2: The role of cementum in root surface
      caries.
AB  - Artificial caries lesions were produced in roots of teeth using an acetate buffer
      system, when the layer of cementum was either normal in thickness, excessively
      thickened by hypercementosis, or had been removed completely. The rates of lesion
      progression were measured in each case using polarized light microscopy to
      measure lesion depth. Analysis of calcium (Ca) and phosphorus (P) loss during the
      demineralizing process was carried out. The removal of cementum was found to
      significantly increase the initial rate of penetration of the lesion into the
      root, although this rate progressively reduced to a level consistent with that
      found in normal roots after seven days of demineralization. The overall depth
      remained consistently greater than that observed in normal roots, or when lesions
      were produced entirely within hyperplastic cementum. Chemical analysis also
      showed removal of cementum resulted in an initial doubling of the Ca and P lost
      from the root surface. Prior direct exposure of segments of normal roots to the
      oral environment was found not to significantly alter the rate of artificial
      lesion progression, in comparison with that in the originally protected segment
      of the root surface. It was concluded that an intact cementum layer has the
      intrinsic ability to protect the underlying dentine of exposed tooth roots
      against acidic demineralization and that prior exposure to the oral environment
      does not significantly alter this ability.

PMID- 10925506
TI  - Hepatitis C infection and associated oral health problems.
AB  - Hepatitis C infection is widespread throughout the community. This study aimed to
      assess the status of oral health of persons infected with hepatitis C. DMFT and
      CPITN indices were recorded at a clinic providing priority dental care for people
      with hepatitis C infection. The data were compared with information from an
      existing survey of general dental patients. Social impact was assessed using a
      modified Oral Health Impact Profile questionnaire. The DMFT index differed
      significantly between hepatitis C and general patients. The number of decayed and
      missing teeth was greater in those infected with hepatitis C for all patients
      aged between 25 and 50 years. Although there was no significant difference in
      CPITN categories for subjects evaluated, a marked trend for poor periodontal
      health was noted for those individuals with hepatitis C. Salivary flow was
      reduced in 50 per cent of hepatitis C infected subjects. Social impact was
      significantly affected with 71 per cent of hepatitis C subjects reporting painful
      aching in the mouth and 56 per cent having difficulty in relaxing. In conclusion,
      the results from the project strongly indicate an urgent need for priority
      delivery of dental care for people with hepatitis C infection.

PMID- 10925505
TI  - Fracture strength of all-ceramic crowns with varying core elastic moduli.
AB  - The aim of this study was to investigate the fracture strength of aluminous
      porcelain jacket crowns on core structures with different elastic moduli. Forty
      standardized aluminous porcelain jacket crowns were fabricated and divided into
      four groups. Each crown was luted with zinc phosphate cement onto a master die
      with a known elastic modulus, and loaded until failure occurred. The fracture
      load was shown to increase with increasing elastic modulus of the core. Analysis
      of data by ANOVA revealed a significant difference (p < 0.05) between the four
      groups. The results suggested that core elastic modulus may have an influence on
      the fracture resistance of aluminous porcelain jacket crowns, and it may be
      appropriate to recommend the use of high modulus metals for core placement on
      teeth to be restored with all-ceramic crowns.

PMID- 10925507
TI  - Clinical evaluation of EBS dentine bonding agent: one year results.
AB  - There are numerous dentine bonding agents currently on the market, the majority
      of which adhere by means of infiltration of a hydrophilic polymerizable
      diacrylate into dentinal collagen exposed by acid treatment. The purpose of the
      present study was to evaluate the clinical performance of one such product, EBS
      dentine bonding, in non-undercut caries-free cervical lesions. Forty cavities
      were restored in eight patients of mean age 53 years. The manufacturer's
      instructions were followed, which involved essentially etching the enamel and
      dentine for 20 seconds with 32 per cent phosphoric acid, application and
      evaporation of EBS Primer, followed by placement and curing of EBS Bond, and
      restoring the cavity with Pertac II (ESPE) hybrid resin composite. Restorations
      were photographed at base line and one year for evaluation of marginal
      discolouration on a continuous linear rating scale. At six months, one patient
      with four restorations was not available; the remaining 36 restorations were all
      present. At one year, one restoration was missing, giving a cumulative retention
      rate of over 97 per cent. One of the 36 restorations exhibited very mild marginal
      discolouration.

PMID- 10925508
TI  - The surface effect of dentifrices.
AB  - The aim of this study was to evaluate clinically three commercially available
      dentifrices and to determine any surface effects on tooth or gingival surfaces.
      Sixty-four participants were included in this study and were allocated randomly
      to one of four treatment groups by an independent person to ensure the
      investigators were unaware of the brushing material used. All toothbrushes and
      dentifrices were distributed by this independent person. The treatment groups
      were: Group 1--brush with water; Group 2--brush with Colgate (Baking Soda and
      Peroxide); Group 3--brush with Macleans (Whitening); Group 4--brush with Colgate
      (Sensation Whitening). All participants were requested to brush both morning and
      evening in their customary fashion using only the designated toothpaste, or
      water, for four weeks. All participants were required to use the same toothbrush
      type. No other oral hygiene products such as mouth rinses or dental floss were
      used during the trial period. Prior to commencement of the brushing period, all
      participants received a full clinical examination recording the status of the
      soft and hard tissues including a gingival index (Loe and Silness) to record
      gingival condition. A polyvinyl siloxane impression was taken of the six anterior
      teeth and gingival tissues at the commencement of the trial. After four weeks, a
      second full clinical examination was made and further silicone impressions were
      taken of the anterior teeth. All impressions were cast in epoxy resin for
      investigation with light and electron microscopy. Participants were also asked to
      answer a questionnaire relating to the toothpaste used. The results of this study
      indicated that no significant clinical differences were recorded for any
      dentifrice or water and there was no significant difference in gingival index
      scores over the four week period. Patient responses to each dentifrice varied
      according to individual patient preferences and expectations and no consistent
      findings could be determined. Light and electron microscopy indicated that tooth
      and gingival surface changes that occurred over the four week period with any of
      the dentifrices were similar to, and not significantly different from, changes
      seen with the use of water alone. These results indicate that none of the
      dentifrices tested was harmful to teeth or soft tissues.

PMID- 10925509
TI  - Clinical assessment in dental education: a new method.
AB  - Among the many challenges that face modern dental schools is the development of
      appropriate assessment systems. The more litigious nature of modern education
      makes it important that the systems developed are transparent and can withstand
      the processes of legal challenge. Coupled with this demand for robust assessment
      is a growing demand from universities and health providers for dental schools to
      keep rigorous records of student clinical productivity. This brief review
      outlines a system developed at the School of Oral Health Sciences at the
      University of Western Australia. The system integrates both qualitative and
      quantitative assessment and uses criterion-based assessment as its foundation.
      Detailed analysis and real-time reporting mechanisms using a suite of personally
      written software tools is now possible. The system provides both students and
      staff with effective data to enhance the learning process.

PMID- 10925510
TI  - Temporary uniocular blindness and ophthalmoplegia associated with a mandibular
      block injection. A case report.
AB  - A mandibular block injection produced temporary uniocular blindness, total
      ophthalmoplegia, mydriasis, and ptosis of the eyelid, with diplopia developing as
      the sight returned. These effects lasted 25-30 minutes. The explanation offered
      as to the cause of the anaesthetic phenomenon is an intra-arterial injection into
      the maxillary artery with backflow of anaesthetic solution into the middle
      meningeal artery. The instantaneous blindness results from the anaesthetic agent
      being carried into the central artery of the retina through an anastomosis of the
      ophthalmic and middle meningeal arteries via the recurrent meningeal branch of
      the lacrimal artery. Although of short duration, the symptoms mimic a more
      serious carotid artery embolus occluding the ophthalmic artery. Complications of
      mandibular blocks have been reported in the literature, however total blindness
      and ophthalmoplegia are extremely rare. This case report highlights an event
      where individual anatomical variation of the maxillary and middle meningeal
      arteries has allowed anaesthetic solution to be delivered to an ectopic site.

PMID- 10925511
TI  - Getting the most from rotational panoramic radiographs.
AB  - Rotational panoramic radiographs have become an invaluable tool in modern
      dentistry. To use the full potential of this resource the entire radiograph must
      be examined in a systematic way to extract the great wealth of information
      available. This paper provides the framework for the development of a systematic
      method to examine panoramic radiographs. The essential elements are that all
      areas of the radiograph should be examined and that there are a number of high
      yield areas with regard to pathology that require special attention.

PMID- 10925512
TI  - Temporomandibular joint arthroscopy.

PMID- 10925513
TI  - [Results of the German investigation in the EU Project "Salmonella in Pork
      (Salinpork)"--2. Investigations in a slaughterhouse].
AB  - In 1997 bacteriological examinations for the distribution of Salmonella in
      slaughterhouses were carried out in Germany within the framework of an
      international study "Salmonella in Pork (Salinpork)". During 6 days, 1,200 swab
      and water samples from slaughtered pigs and the environment were taken. 4.4% of
      the samples (n = 53) were Salmonella positive. S. typhimurium was isolated mainly
      (69.8%; n = 37), and 6 phagetypes were differentiated. In addition, S. derby and
      S. panama could be demonstrated. The resistance pattern of the different isolated
      S. typhimurium-phagetypes are presented. The phagetype DT 104 was multiresistant
      to ampicillin, spectinomycin, streptomycin, sulphonamide and tetracycline. In
      comparison with the serological prevalence of 7.3% of the fattening pigs in the
      farms (Part 1), only 1.0% of the samples taken from the surface of the carcass
      were Salmonella-positive. Swabs taken from the liver were in 2.7% positive and
      samples from the tongue gave in 5.3% of the cases Salmonella-positive results. In
      the examination of the environment Salmonella was demonstrated mainly from the
      water outlets, whereas Salmonella could not be isolated from water of the
      scalding tank. There was only one case (0.7%) in which Salmonella could be
      isolated from the hands of the personnel, and also only one swab of the polishing
      machine was positive (1.1%). But 6.7% samples of the saw were Salmonella
      positive. A comparison of repeated, at intervals taken samples showed that the
      number of Salmonella-positive samples was higher in the last examination round of
      the particular slaughter days. The reason is suspected in the increasing number
      of slaughtered pigs and supplying farms, which may increase the probability of
      bringing in Salmonella.

PMID- 10925514
TI  - [Sensitivity of bovine and equine streptococci to beta-lactam antibiotics
      (benzylpenicillin, ampicillin, oxacillin, cefotaxime) in the agar diffusion and E
      test].
AB  - 368 streptococcal strains from udder secretions of cattle (Sc. agalactiae, Sc.
      dysgalactiae, Sc. uberis) and 191 streptococcal isolates from horse specimens
      (Sc. equi ssp. zooepidemicus, Sc. equi ssp. equi) originating from different
      agricultural regions in Germany (Lower Saxony, in particular the region of Weser
      Ems, Bavaria, Altmark) were investigated for their sensitivity to 4 beta-lactam
      antibiotics (benzylpenicillin, ampicillin, oxacillin, cefotaxime). Two different
      test methods were applied: the agar diffusion test for determination of the
      diameter of the zone of inhibition and the E-test for determination of the
      minimal inhibitory concentration (MIC). According to the evaluation code of DIN
      58,940, 98% to 100% of the isolates from the cow udder as well as of the
      Streptococcus strains from horses were sensitive to the four antibiotics tested.
      Only Sc. uberis was less sensitive to benzylpenicillin (79.7%) and Oxacillin
      (83.2%). The strains from different agricultural regions did not differ from each
      other concerning their sensitivity to beta-lactams. The results of the two
      methods of sensitivity testing were in satisfactory agreement: Compared to the
      MIC reference values, misclassifications occurred in the agar diffusion test only
      at an error rate of between 1.62% (for ampicillin) and 5.21% (for
      benzylpenicillin).

PMID- 10925516
TI  - [Occurrence of various immunoglobulin isotopes in horses with equine recurrent
      uveitis (ERU)].
AB  - We investigated 30 healthy eyes and 41 eyes with ERU from 57 horses. The total
      immunoglobulin titers and titers of IgGa, IgGb, IgM were measured in aqueous
      humour, vitreous and serum using different ELISA techniques. Every sample
      investigated contained detectable amounts of immunoglobulins. Compared to control
      eyes significantly increased titers were found in the aqueous humour and vitreous
      of the ERU eyes for all immunoglobulin isotypes studied (p < or = 0.01). While
      IgM was detected in only 2 out of thirty aqueous humour and in none of the thirty
      vitreous samples of healthy eyes, 79.6% of samples of ERU eyes revealed
      considerable IgM titers. Changes of the IgGa/IgGb ratio in the eye as compared to
      that in the autologous serum was more frequent in affected than in healthy eyes.
      In contrast to the intraocular immunoglobulins there were no significant
      differences in immunoglobulin serum titers in healthy horses and those affected
      with ERU (p > 0.05). In conclusion, the results argue for a physiological
      appearance of immunoglobulins in the healthy eye. The increased titers of
      immunoglobulins in eyes stricken with ERU might be signs either of a local ocular
      production of antibodies and/or an increased permeability of intraocular
      barriers.

PMID- 10925515
TI  - [A new live Salmonella enteritidis vaccine for chickens--experimental evidence of
      its safety and efficacy].
AB  - Within the works for the registration of a new live Salmonella Enteritidis
      vaccine for layers, safety and efficacy of the vaccine strain were tested by
      experimental studies. After oral administration of the single and the tenfold
      dose, no incompatibility reactions were seen in day-old chicks. The laying
      performance and the egg weight were not affected by the vaccination of the
      chickens during the laying period. There was only a limited period in which the
      excretion of the vaccine strain and its persistency in organs were seen. Even
      after the threefold oral vaccination the vaccine strain could not be isolated
      from eggs and internal organs of slaughtered chickens. Moreover, a high safety
      for non-target animals (cattle, pigs) could be established. Studies with BALB/c
      mice proved that a cell-mediated immunity and the development of complement
      fixing antibodies is induced by the vaccine. Efficacy studies in target animals
      were carried out by a proved dependable oral challenge system that reproduces a
      latent infection with marked S. Enteritidis strains and by means of the seeder
      bird method. The test results demonstrate that the vaccination is capable to
      avert or to reduce an infection significantly.

PMID- 10925517
TI  - [Multifunctional testing of PTCA balloon catheters].
AB  - New in vitro measuring methods for balloon catheters used for percutaneous
      transluminal coronary angioplasty (PTCA) and their verification in a complex test
      device are presented. This system can mimic all relevant application situations.
      The central element of the test device is a coronary vessel model matching the
      physiological situation in terms of geometrical structure and frictional
      properties. Reactive force sensors are used to measure the application-relevant
      forces exerted by the catheter on the model vessel walls and accessories, such as
      guide wire and guiding catheter. To generate a kink-free advancement of the
      catheter and permit measurement of the active forces, an alternating drive unit
      has been specially developed. The testing and application of the newly developed
      methods revealed statistically significant differences between various types of
      catheter. The test device closes a gap between complex but subjective clinical
      tests, and individual objective, but application-removed in vitro test setups for
      PTCA catheters. While the initial prototype had shortcomings with regard to the
      reproducibility of measurements, successor systems developed for industrial use
      are now in production. The properties of these measuring systems developed for
      the benefit of manufacturer and reprocessor of PTCA catheters are discussed.

PMID- 10925518
TI  - [A simple model for describing pressure-volume curves in free balloon dilatation
      with reference the dynamics of inflation hydraulic aspects].
AB  - We propose a simple model to describe pressure-time and pressure-volume curves
      for the free balloon (balloon in air) of balloon catheters, taking into account
      the dynamics of the inflation device. On the basis of our investigations of the
      flow rate-dependence of characteristic parameters of the pressure-time curves,
      the appropriateness of this simple model is demonstrated using a representative
      example. Basic considerations lead to the following assumptions: (1) the flow
      within the shaft of the catheter is laminar, and (ii) the volume decrease of the
      liquid used for inflation due to pressurization can be neglected if the liquid is
      carefully degassed prior to inflation, and if the total volume of the liquid in
      the system is less than 2 ml. Taking into account the dynamics of the inflation
      device used for pumping the liquid into the proximal end of the shaft during
      inflation, the inflation process can be subdivided into the following three
      phases: initial phase, filling phase and dilatation phase. For these three
      phases, the transformation of the time into the volume coordinates is given. On
      the basis of our model, the following parameters of the balloon catheter can be
      determined from a measured pressure-time curve: (1) the resistance to flow of the
      liquid through the shaft of the catheter and the resulting pressure drop across
      the shaft, (2) the residual volume and residual pressure of the balloon, and (3)
      the volume compliance of the balloon catheter with and without the inflation
      device.

PMID- 10925519
TI  - Haemocompatibility of coronary catheters.
AB  - BACKGROUND: Unwanted side-effects like thrombotic-thromboembolic processes
      accompany the intravascular use of catheters. The influence of the physico
      chemical properties of the catheter materials on these processes is not
      completely understood. METHODS: The haemocompatibility of angiography-catheters
      (n = 10) (Super Torque Plus, CORDIS, Johnson & Johnson company) was examined in a
      perfusion-model filled with platelet-rich plasma and either compared to a non
      thrombogenic (silicon-tube) or to a thrombogenic surface (glass). As test
      parameters the number of single circulating thrombocytes, of circulating platelet
      aggregates, of circulating activated thrombocytes (CD62) and the thrombin
      generation (thrombin antithrombin III-complexes) were evaluated. RESULTS: None of
      the test-parameters showed differences between the non-thrombogenic control
      system and the angiography-catheters. Both systems, however, differed
      significantly and relevantly from the system filled with the glass-beads (the
      thrombogenic control-systems). CONCLUSION: With respect to the platelet
      reactivity angiography-catheters of the examined type can therefore be regarded
      as non-thrombogenic or haemocompatible.

PMID- 10925520
TI  - [Legal aspects of reuse and re-sterilization of disposable products in the
      hospital].
AB  - What consequences may follow if the hospital administration decides to introduce
      recycling and resterilisation of disposable medical products? While some consider
      the chief executive administrators and doctors to be seriously endangered by the
      legal implications of the German Medical Products Act (MPG), others consider
      recycling and resterilisation to be clearly admissible. A closer look at what
      constitutes an offence as described in sec. 43, para 1 No. 1 of the MPG reveals
      that mere presumptions do not suffice to incur the respective penalties; rather,
      a concrete, scientifically sound basis for assuming an endangerment of safety or
      health are required for penal measures to be justified. The manufacturer's
      designation "for once-only use" may not be considered "intended purpose" as
      stipulated in sec. 4, para 1 No. 1 of the MPG. If recycling or resterilisation be
      confined to self-made disposables, there is no necessity for CE marking.
      Information of the patient and individual documentation must be extended to cover
      the use of recycled or resterilised disposable products only if the use of the
      latter may constitute a significant additional danger to the patient.

PMID- 10925521
TI  - [Reuse of instruments for minimal invasive surgery--status and prospects].
AB  - The development of instruments for minimal invasive surgery (MIS) is moving in
      the direction of the miniaturization of mechanical components, a combination of
      multiple functions in a single instrument, and the introduction of new
      techniques, in particular those reducing bleeding and thermal damage when cutting
      blood vessels. These tendencies have consequences for the reprocessability of the
      instruments, usually making reprocessing more difficult. In particular cleaning-
      the removal of contaminations from tiny lumina, joints, etc., is highly
      demanding. In addition, proof of successful cleaning is difficult, and no
      standardised method of doing this in practice is currently available. An overview
      of the problems associated with the reprocessing of instruments for minimal
      invasive surgery is given, and a numbers of possible solutions are discussed.

PMID- 10925522
TI  - [Therapeutics for future treatment of uveitis].
AB  - The increased knowledge in immunology and the progresses of pharmacology have
      improved our treatment of autoimmune diseases. The main anti-inflammatory effects
      of corticosteroids are an attenuation of the hypersensibility reactions, a
      sequestration of intravascular lymphocytes and an inhibition of the production of
      cytokines and eicosanoids. The non-steroidal anti-inflammatory drugs (NSAID's)
      form another group of medications particularly useful for the treatment of
      chronic uveitis. Several Cox-2 inhibitory medications are at the moment under
      clinical investigation and some are commercially available. One of their
      characteristics is to present less of the most undesirable side effects seen with
      conventional NSAID's like irritation of the gastro-intestinal tractus and
      platelets aggregation inhibition. Agents like cyclophosphamide, leukeran, imuran,
      methotrexate and cyclosporin have been used extensively for the treatment of
      severe uveitis. Because of its efficacy and safety, methotrexate is the best
      immunosuppressive agent to be tried for the treatment of chronic uveitis.
      However, immunosuppressive treatments and corticosteroids have many side effects
      and are not very selective. To improve our therapeutic arsenal, other treatments
      are being investigated for the treatment of severe uveitis. Manipulations of
      cytokines expression by Th1 lymphocytes will be one of then.

PMID- 10925523
TI  - The combined IOP and CCT measurement in glaucoma screening.
AB  - In a prospective study we measure the intra-ocular pressure (IOP) by means of a
      pneumotonometer and the central corneal thickness (CCT) in 245 healthy emmetropic
      or ametropic eyes consulting in a private practice. There is a linear relation
      between IOP measurement and CCT. The same measurements are done in 30
      glaucomatous eyes and in 16 eyes with ocular hypertension. The mean CCT is
      similar in normal and glaucomatous eyes (554 mu). In eyes with ocular
      hypertension there is a manifest elevated CCT.

PMID- 10925524
TI  - The correlation between IOP measurement, central corneal thickness and corneal
      curvature.
AB  - In a prospective study we measured the intraocular pressure (IOP), the central
      corneal thickness (CCT) and the central corneal curvature in 172 myopic eyes
      before and after LASIK treatment. We find a significant decrease in intraocular
      pressure. Statistical evaluation reveals a linear correlation between the IOP
      decrease and the amount of stromal ablation. The IOP and corneal curvature are
      measured in 21 hyperopic eyes before and after LASIK treatment. We do not find a
      change in the IOP. In a retrospective study of 47 myopic eyes before and after
      RADIAL KERATOTOMY we find no change in IOP. We conclude that CCT is important in
      evaluating the IOP and that corneal curvature has little effect on IOP
      measurement.

PMID- 10925525
TI  - [An alternative treatment for amblyopic strabismus: optical penalization].
AB  - The aim of this study is to demonstrate the efficacy of the systematic
      prescription of an overcorrection of +2 to +2.5 D in 89 patients with a
      persisting pathological dominance of fixation after treatment by prisms and
      calibrated filters. The second criterion of prescription was the absence of any
      short term surgical plan. The percentage of compliance was 89% but 93.5% of the
      patients achieved a visual acuity > or = to 7/10. Besides the visual result, this
      method improved the motor instability in 68% of strabismic patients with a
      deviation of 10 to 20 PD. Two cases recovered a normal retinal correspondence and
      a stereoacuity of 60" measured at the TNO test. The mean age of the optical
      penalization is 5.2 years (range: 2 to 10.5 y.) and the mean duration 2.3 y.
      (range: 0.5 to 4.5 y.). The minimal age of evaluation was 7 y. This method is
      simple and efficient and appears to be the best way to the long term success of
      strabismic functional amblyopia.

PMID- 10925526
TI  - [Vitrectomy for diabetic macular edema associated with hyaloid posterior
      traction].
AB  - The vitreomacular relationship has been demonstrated to play a role in the
      physiopathology of the diabetic macular edema. We review the functional and
      anatomic results of vitrectomy performed on four eyes of three patients with
      diabetic cystoid macular edema unresolved by photocoagulation. The preoperative
      visual acuity was "finger counting" at one meter to 1/20. After surgery, for
      three eyes, the visual acuity raised between 2/10 and 4/10. There was no change
      for one eye, which presented a subretinal fibrosis. The macular edema resolved in
      three eyes and improved in one eye. The mean postoperative follow-up is 13
      months. The vitrectomy may be effective in cases of diabetic macular traction and
      edema without posterior vitreous detachment.

PMID- 10925527
TI  - Spontaneous corneal perforation and endophthalmitis in Pseudomonas aeruginosa
      infection in a ventilated patient: a case report.
AB  - We report a case of Pseudomonas keratitis and endophthalmitis after inoculation
      from the respiratory tract in a mechanically ventilated patient. In these
      (semi)comatose and more vulnerable patients, colonisation of the upper
      respiratory tract by Pseudomonas occurs frequently, and this can lead to
      inoculation of the eyes. Emphasis lies on careful prevention of ocular
      inoculation and aggressive therapy as soon as keratitis is noticed.

PMID- 10925528
TI  - [Non perforating trabecular surgery with reticulated hyaluronic acid implant].
AB  - Non perforating trabecular surgery (NPTS) with reticulated hyaluronic acid
      implant (Skgel) allows aqueous humor to leave anterior chamber through a thin
      trabeculo-Descemet's membrane into a sclerocorneal space filled with Skgel
      implant and then via the outflow physiological channels. Good IOP results are
      obtained with less or without external filtration decreasing the incidence of per
      and postoperative complications described after trabeculectomy. This surgery is
      actually only indicated for primary open angle glaucoma, the trabeculectomy still
      remaining the gold standard procedure for the other glaucoma cases.

PMID- 10925529
TI  - Effect of non-steroidal anti-inflammatory drugs (NSAID) on the rabbit corneal
      epithelium studied by scanning electron microscopy.
AB  - We investigated the effect of 6 commercially available non-steroidal anti
      inflammatory drug (NSAID) eye drops on the normal corneal epithelium of rabbits.
      Each drug was instilled into both eyes of 2 rabbits, 5 times a day, for 5
      consecutive days. Two additional corneas of one rabbit, without any treatment,
      served as control. After treatment, the corneas were excised and processed for
      scanning electron microscopic evaluation. The epithelial changes induced by the
      drugs were graded by an empirical score system. All test compounds caused
      alterations in the cell membranes and surface microvilli, or even exfoliation and
      necrosis of surface cells. The extent of cell damage appeared to be related to
      the active ingredient in the eye drops, the pH of the solution, and the
      constituents of the vehicle, especially the type of preservative used.

PMID- 10925530
TI  - No efficacious treatment for age-related macular degeneration.
AB  - PURPOSE: The purpose of this paper is to explain that many trials have been done
      unsuccessfully to improve age-related macular degeneration. METHODS: Different
      trials that have been done to improve this degeneration and that have been
      published in a peer reviewed journal are discussed. RESULTS: There is not yet a
      preventive therapy that has a significant impact on blindness due to age-related
      maculopathy. There is no therapy for geographic atrophy. There are limited forms
      of therapy with the objective of destroying new vessels arising in the choroid
      and of limiting the visual loss. CONCLUSION: There is a need for more efforts to
      find ways that influence the survival of the complex photoreceptor--retinal
      pigment epithelium--Bruch's membrane in the aging population.

PMID- 10925532
TI  - In vitro activity of quinupristin/dalfopristin against gram-positive bacteria
      Haemophilus influenzae and Branhamella catarrhalis in Taiwan.
AB  - BACKGROUND: Over the past decade, resistance of Gram-positive cocci to common
      antibiotics has steadily increased. New antibacterial agents that are active
      against multidrug-resistant pathogens are urgently needed for the treatment of
      these pathogens. We conducted an in vitro study on the activity of
      quinupristin/dalfopristin and other antibiotics against common clinical isolates
      of the gram-positive cocci, Haemophilus influenzae and Branhamella catarrhalis.
      METHODS: The agar dilution method described by the National Committee for
      Clinical Laboratory Standards was used to determine the minimum inhibitory
      concentrations (MICs) of bacterial isolates from clinical specimens obtained from
      patients in a medical center. RESULTS: All Staphylococcus aureus isolates were
      inhibited by quinupristin/dalfopristin (< or = 2 micrograms/ml). The MIC90s were
      1 mg/ml for both methicillin-sensitive and -resistant S aureus.
      Quinupristin/dalfopristin inhibited streptococci at a concentration of 1
      microgram/ml or less. The MIC90s were 1 microgram/ml for Streptococcus
      pneumoniae, S pyogenes and viridans streptococci. Ampicillin-resistant
      Enterococcus faecium was inhibited by quinupristin/dalfopristin at 0.5 to 4
      micrograms/ml, with an MIC90 of 1 microgram/ml. H influenzae was inhibited by
      quinupristin/dalfopristin at 0.25 to 8 micrograms/ml, with an MIC90 of 4
      micrograms/ml. B catarrhalis was inhibited by quinupristin/dalfopristin at 0.25
      to 1 microgram/ml, with an MIC90 of 1 microgram/ml. CONCLUSIONS: We found that
      quinupristin/dalfopristin showed good in vitro activity against staphylococci,
      streptococci and B catarrhalis but less in vitro activity against H influenzae.

PMID- 10925531
TI  - Multifocal intraocular lens implantation in patients with presenile unilateral
      primary and secondary cataract.
AB  - Multifocal intraocular lens implantation was studied in 6 eyes with a unilateral
      cataract due to ocular trauma. Two patients had an uncomplicated traumatic
      cataract, two patients had a complicated traumatic cataract and two patients had
      a unilateral primary presenile cataract. Postoperative visual acuity for distance
      and for near vision, with and without additional spectacle correction, as well as
      the presence of postoperative binocular vision was evaluated. Additionally, we
      looked for pre- and postoperative parameters, assuming these criteria determine
      the success ratio of a multifocal intraocular lens implantation: presence of a
      stereoscopic vision pre-operatively, or absence of a pre-operative strabismus;
      rather good visual prognosis (no retinal damage in the traumatic cases and no
      amblyopia in the primary cases); normal functioning of the pupillary sphincter.

PMID- 10925533
TI  - Significance of specific IgG subclass antibodies to house dust mites in asthmatic
      children.
AB  - BACKGROUND: Dermatophagoides pteronyssinus (Dp) and Dermatophagoides farinae
      (Df), the major components of house dust, are considered to be etiologic factors
      of extrinsic asthma. The relationships between immunoglobulin (Ig) G subclass
      antibodies specific for Dp (or Df) were compared in specific IgE-positive and 
      negative asthmatic children. METHODS: Serum levels of IgG and IgE subclass
      antibodies specific for Dp and Df were studied in 52 children (age, 3-13 years;
      mean age, 8.4 years) with asthma using enzyme-linked immunosorbent assays. The
      skin prick test was also used in diagnosis of the reactivity of allergic disease.
      RESULTS: The levels of serum-specific IgG1 and IgG2 to Dp and Df in mite-specific
      IgE-(or skin-test) positive asthmatic children were significantly higher than
      those in mite-specific IgE- (or skin test) negative children (p < 0.01).
      Significant correlations between the level of the specific IgE and IgG1 (r =
      0.6067; p = 0.0001) or IgG2 (r = 0.5851; p = 0.0002) to Dp, and IgG1 (r = 0.3823;
      p = 0.0214) or IgG2 (r = 0.5057; p = 0.0017) to Df were found. The specific IgE
      level and skin test reactivity showed a high correlation of greater than 96%
      (50/52). CONCLUSIONS: The levels of mite-specific IgG subclasses were partially
      compatible to specific IgE levels and skin test reactivity. We conclude that
      house dust mite allergy is significantly associated with specific IgG1, IgG2 and
      IgE responses.

PMID- 10925534
TI  - Obliterated processus vaginalis diagnosed by intraoperative laparoscopy is
      unlikely to develop into a clinical hernia.
AB  - BACKGROUND: This study was conducted to evaluate if a subsequent inguinal hernia
      would occur in the contralateral obliterated processus vaginalis shown by
      intraoperative laparoscopic examination. METHODS: From July, 1993 to February,
      1994, 120 patients with a unilateral inguinal hernia were identified as
      obliterated processus vaginalis by intraoperative laparoscopic examination of the
      contralateral internal ring when they received unilateral herniorrhaphy. A five
      year follow-up of the contralateral side to determine the rate of subsequent
      inguinal hernia was carried out during an outpatient clinic check-up or by
      telephone contact. RESULTS: One patient, among the first few patients having
      laparoscopic examinations, had a subsequent contralateral inguinal hernia. Two
      patients had hydroceles and each of the operative findings was a communicating
      hydrocele that could not possibly develop into a clinical hernia. CONCLUSIONS: It
      is unlikely for an obliterated processus vaginalis indicated by intraoperative
      laparoscopic examination to become a clinical inguinal hernia.

PMID- 10925535
TI  - Surgical treatment of full thickness rotator cuff tear in patients younger than
      40 years.
AB  - BACKGROUND: Full thickness tear of the rotator cuff is a well-known entity in the
      middle-aged and elderly population and the results of surgical repair are well
      documented. Rotator cuff tear in patients under the age of 40 years is unusual
      and the cause and treatment are not well established. The present study reports
      12 young patients with full thickness tear of the rotator cuff treated
      surgically. METHODS: Open anteroinferior acromioplasty and cuff repairs were
      performed on every patient after failure of nonsurgical treatment. The average
      follow-up was 59.5 months (range, 36-100 months). RESULTS: The average patient
      age at the time of surgery was 30.2 years (range, 17-39 years). Symptoms included
      pain and dysfunction in all patients and weakness in eight patients. The duration
      of symptoms before surgery ranged from 6 to 60 months (average, 22.8 months). Ten
      patients were able to return to their preinjury status within an average of 4.5
      months (range, 3-9 months) after surgery. Three athletes were able to return to
      previous levels of competition. Nine patients had excellent functional results
      with regard to pain, motion, strength, function and satisfaction. Eleven patients
      were satisfied with the operation and had significant pain reduction compared
      with their preoperative status. CONCLUSIONS: An acute traumatic event was the
      etiology of the rotator cuff tears in this study. The results of surgical
      treatment in this younger group of patients were satisfactory and were comparable
      to the outcomes reported for surgical treatment of rotator cuff tears in older
      patients and athletes.

PMID- 10925536
TI  - Treatment of non-small-cell lung cancer: the Chinese experience in a general
      teaching hospital.
AB  - BACKGROUND: It has been reported that combination chemotherapy and radiotherapy
      prolongs locally advanced stage IIIB non-small-cell lung cancer (NSCLC) patient
      survival and cisplatin-based chemotherapy prolongs survival in stage IV disease.
      This study was aimed at investigating whether this conclusion also applies to
      Chinese patients. METHODS: We retrospectively reviewed the medical records of
      NSCLC patients diagnosed at the Taipei Veterans General Hospital covering a
      period from 1990 to 1996 to examine the effect of treatment regimen on survival.
      RESULTS: There were 3,925 cases of NSCLC diagnosed during this period. The stage
      at diagnosis was stage III or IV in the majority (76.6%) of cases. Surgery
      followed by chemotherapy with or without radiotherapy conferred a survival
      benefit of more than two years in stage IIIA patients. For stage IIIB patients,
      chemotherapy in combination with radiotherapy yielded a median survival of 13
      months, compared to only seven months for radiotherapy alone. For stage IV
      patients, cisplatin-based chemotherapy prolonged median survival for more than
      two months compared with palliative radiotherapy alone or supportive care only.
      Survival was improved in stage IV patients who received chemotherapy during 1990
      to 1996 compared with those who received chemotherapy during 1985 to 1989. This
      improvement was most likely due to improvements in supportive care because the
      treatment regimen was constant during the study period. CONCLUSIONS: Cisplatin
      based chemotherapy prolonged survival of Chinese patients with metastatic NSCLC.
      Combination chemotherapy and radiotherapy also prolonged survival of Chinese
      patients with locally advanced NSCLC.

PMID- 10925537
TI  - Effects of glucose-free maintenance solution on plasma glucose during anesthesia
      in patients undergoing long neurologic surgery.
AB  - BACKGROUND: Using glucose-free solution as fluid maintenance is widely advocated
      during neurosurgery because of concerns about hyperglycemia aggravating cerebral
      ischemia. This study evaluated the alterations in plasma glucose concentrations
      in both adult and pediatric patients undergoing lengthy neurologic surgery,
      during which they were given glucose-free solutions. METHODS: This study included
      154 patients (ASA class II, aged 3 months-75 years) undergoing elective
      neurosurgical procedures. They were divided into two groups: group A (15-75 years
      of-age) and group P (3 months-14 years-of-age). Groups A (n = 126) and P (n = 28)
      were further divided into five subgroups, respectively, based on the duration of
      surgery: 5, 6, 7, 8 and 9 hours. Anesthesia was maintained with isoflurane,
      fentanyl and vecuronium. Blood sampling was undertaken every hour throughout
      surgery. RESULTS: Adult patients differed significantly in body weight (61.5 +/-
      10.9 vs 25.6 +/- 14.9 kg), age (58.9 +/- 15.7 vs 7.5 +/- 4.3 years), use of
      preoperative beta-blocking agents (33/126 vs 1/28) and the need for blood
      transfusion (58/126 vs 24/28). Neither group had elevated glucose levels.
      Compared with pediatric patients, the incidence of intraoperative hypoglycemia
      was statistically higher in adult patients, with a rate that peaked in the eighth
      (25.9%, group A vs 0% group P) and ninth hours (27.3%, group A vs 0% group P) of
      surgery. There were no differences in glucose concentrations at other points in
      time. CONCLUSIONS: In contrast to pediatric patients, intraoperative hypoglycemia
      occurred more often in adult patients during prolonged neurosurgical procedures
      when glucose-free solution was used for fluid maintenance. Therefore, frequent
      determination of plasma glucose concentrations is mandatory, especially in
      patients undergoing long-lasting neurosurgical anesthesia.

PMID- 10925538
TI  - High resolution MRI of adrenal glands in patients with primary aldosteronism.
AB  - BACKGROUND: We studied the role of high-resolution magnetic resonance imaging
      (MRI) of the adrenal glands using a surface coil in patients with primary
      aldosteronism to differentiate aldosterone-producing adenomas (APA) from
      idiopathic hyperplasia of the adrenal gland (IHA). The data obtained were used to
      decide on surgical or nonsurgical treatment for patients. METHODS: High
      resolution MRI with SE T1WI, FSE T2WI and paired in- and out-phase images of the
      adrenal glands of 41 patients with clinically documented primary aldosteronism
      were collected. The images were reviewed in comparison with other differentiating
      tests. RESULTS: Nineteen of the 41 patients were diagnosed with APA on MRI.
      Surgical and pathologic proof of APA was obtained in 10 cases and solitary
      macronodular hyperplasia was found in one case. Among these 11 cases, there were
      no false positive findings on MRI, while correct detectability of high-resolution
      computerized tomography (CT) was 62.5% (5/8); for adrenal venous sampling, it was
      37.5% (3/8); and for NP-59 adrenal scanning, it was 42.9% (3/7). In eight cases
      with biochemically favored APA and no surgical proof, MRI and CT showed the same
      lesion detection rate, while there was no concordance with venous sampling, and
      concordance of only 33.3% (2/6) for adrenal scanning. In the remaining 22
      patients without focal lesions on MRI, there was poor concordance among the four
      test modalities, with frequently conflicting results. CONCLUSIONS: In patients
      with definitive results of noninvasive biochemical tests for APA, and positive
      findings of unilateral, focal adrenal lesion on MRI or CT, unilateral
      adrenalectomy may be justified without further tedious and invasive examinations.
      CT should still be the first screening test; however, high-resolution MRI is a
      useful diagnostic supplement for patients with strong clinical evidence of APA
      and negative or equivocal findings on CT.

PMID- 10925539
TI  - Cecal volvulus: report of seven cases and literature review.
AB  - BACKGROUND: Cecal volvulus is an abdominal emergency and delay in its diagnosis
      and treatment can result in severe complications. We reviewed these cases in
      order to increase the understanding of cecal volvulus (CV) to promote early
      diagnosis and better management. METHODS: In this retrospective study of seven
      patients (all male; mean age +/- standard deviation, 63.4 +/- 17.3 years) over a
      16-year period, we reviewed radiographs, for diagnostic accuracy, and the results
      of surgical procedures for better future management. RESULTS: The symptoms of CV
      related to obstruction had a mean of duration of 6.85 days (range, 2-20 days).
      The preoperative diagnosis rate was 57.1%. Three types of CV (bascule, clockwise
      and counterclockwise) were found. There were three treatment failures resulting
      in two deaths. There were two cases of metachronous volvulus, one in the sigmoid
      colon and one in the small intestine. CONCLUSIONS: Resection is indicated for
      gangrene or perforation and is highly suggested in underlying bowel disease or
      recurrent operative procedures. For uncomplicated viable CV, cecopexy provides
      fair results. Metachronous volvulus should always be considered when obstruction
      recurs.

PMID- 10925540
TI  - Parkinson's disease with recurrent pulmonary embolism.
AB  - A patient with Parkinson's disease was admitted because of recurrent chest pain
      and dyspnea. Based on high clinical suspicion and a high-probability lung scan,
      the diagnosis of pulmonary embolism was made. Anticoagulation therapy was
      administered and the patient remained free of symptoms during the follow-up
      period of two years. Pulmonary embolism is reported as a possible adverse
      reaction to levodopa therapy and a frequent, but under-recognized cause of death
      in patients with parkinsonism. Clinicians should think of pulmonary embolism, a
      common yet difficult diagnosis, when a parkinsonian patient presents with chest
      pain and dyspnea.

PMID- 10925541
TI  - Malignant meningioma with rhabdoid transformation.
AB  - We report a rare case of recurrent meningioma with malignant change and rhabdoid
      transformation in a 54-year-old woman who presented with severe headache and
      progressive weakness of the right extremities. The patient had a history of
      atypical meningioma and had undergone a craniotomy to remove a tumor nine years
      earlier. We discuss the distinctive morphologic, immunohistochemical staining and
      ultrastructural features of a recurrent malignant meningioma. A meningioma with
      rhabdoid transformation may indicate aggressive biologic and clinical behavior of
      the tumor.

PMID- 10925542
TI  - Primary antiphospholipid syndrome manifested as venous stasis retinopathy.
AB  - Primary antiphospholipid syndrome is a condition in which antiphospholipid
      antibodies may be present without any associated medical disorder. Thrombosis is
      the hallmark of this syndrome. We report the case of a 22-year-old female with
      the chief complaint of floating spots in the right eye for two months. No
      underlying connective tissue disease or systemic disease was noted. Ophthalmic
      examination revealed retinal hemorrhage, retinal vein engorgement and optic disk
      swelling in the right eye only, and normal visual acuity in both eyes. Retinal
      fluorescein angiography showed venous stasis and branch vein leakage in the right
      eye. An antibody profile revealed the presence of immunoglobulin G
      anticardiolipin antibodies, which confirmed the diagnosis of primary
      antiphospholipid syndrome.

PMID- 10925543
TI  - Postcallosotomy seizure outcome in hemiconvulsion-hemiatrophy-epilepsy syndrome.
AB  - Recently, three patients with hemiconvulsion-hemiplegia-epilepsy syndrome who
      underwent callosotomy were monitored for more than four years. All patients had
      atrophy of the right brain hemisphere with left hemiparesis and seizures. Two
      cases were probably the result of traumatic intracranial hemorrhage and one was
      due to an unknown cause. Wada tests were done in cases 1 and 2, which showed
      spared motor function of the atrophic hemisphere, supporting the choice of
      callosotomy instead of hemispherectomy. Patient 1 had atypical absence seizures
      and asymmetric generalized tonic seizures before surgery, the latter of which
      decreased by about 60% after callosotomy. Patient 2 had simple partial seizures
      of the motor type and complex partial seizures, the latter of which were also
      induced by touch (somatosensory-induced reflex epilepsy). This patient's complex
      partial seizures disappeared completely, but the simple partial seizures remained
      unchanged. Patient 3 had generalized tonic seizures, simple partial seizures of
      the sensory type and complex partial seizures. After surgery, the frequency of
      the generalized tonic seizures decreased more than 90%. The simple partial
      seizures of the sensory type remained unchanged. There were two new types of
      seizures after surgery, simple partial seizures of the motor type and brief
      generalized myoclonic jerks. All patients had significant reductions in numbers
      of seizures of more than 50%.

PMID- 10925544
TI  - [The official pharmacy: present and future].

PMID- 10925545
TI  - [The development of hospital pharmacy in Belgium (1975-1998): from the buyer
      retailer to dispenser of drugs, adapting to the needs of the patient].

PMID- 10925546
TI  - [European drugs: Europe faces the future].

PMID- 10925547
TI  - [Problems of pharmacy in Africa].

PMID- 10925548
TI  - [Polyalkylcyanoacrylate microspheres: a hepatic vector or a "furtive" vector].

PMID- 10925549
TI  - Effectiveness of an organ-sharing program in providing zero HLA-A,B,DR mismatched
      kidneys for transplantation in Taiwan.
AB  - PURPOSE: This study evaluated the effects of organ sharing on the allocation of
      kidneys from cadaveric donors to uremic patients from National Cheng Kung
      University Hospital (CKUH) and National Taiwan University Hospital (NTUH) who
      were waiting for kidney transplantation. METHODS: Standard complement-dependent
      microcytotoxicity assays were used. Human leukocyte antigen (HLA)-A,B,C typing
      was performed on nylon-wool-enriched T lymphocytes. HLA-DR typing was performed
      on either nylon-wool-separated B cells or Dynabeads. Isolation of class II
      positive cells was performed with commercial typing trays. RESULTS: Organs were
      allocated from a total of 88 cadaveric donors to 320 patients treated at CKUH and
      179 patients treated at NTUH. Cadaveric kidneys could be allocated with an A,B,DR
      mismatch to 6.9% of CKUH patients and to 4.7% of NTUH patients. When CKUH and
      NTUH patients were pooled, the total number of kidneys that could be allocated
      with 0-A,B,DR mismatch increased to 13.3% (p < 0.004). However, when allocation
      was assessed using 10,000 potential bone marrow donors instead of the 88
      cadaveric donors, kidneys could have been allocated with 0-A,B,DR mismatch to 12%
      (p = 0.64) of patients. No significant benefit was found when allocation
      estimates from the 10,000 potential bone marrow donors were compared with those
      for the 88 cadaveric donors. Use of epitope matching resulted in a 0-A,B cross
      reactive epitope group, and a 0-DR mismatch allocation rate of 36.4% in CKUH
      patients and 31.8% in NTUH patients. This rate increased to 54.6% (p < 0.001)
      when the patients from these hospitals were pooled. CONCLUSION: The results of
      this study demonstrate that the pooling of patients among regional transplant
      centers in Taiwan can significantly enhance the benefits of an organ donation
      program through better HLA matching.

PMID- 10925550
TI  - Risk factors for renal allograft survival in patients receiving cyclosporine
      immunosuppression.
AB  - BACKGROUND AND PURPOSE: Although cyclosporine (CsA) has been widely used in renal
      transplantation for more than 10 years, no large series of renal transplant
      patients has been studied in southern Taiwan. The purpose of this retrospective
      cohort study was to investigate the risk factors for graft survival in renal
      transplant recipients. METHODS: From August 1987 to January 1998, 101 primary
      cadaveric renal transplantations were performed. The minimum follow-up period was
      1 year. CsA and prednisolone were initially used as immunosuppressive agents in
      all patients. Use of lower doses of CsA to reduce CsA trough level (50-99 ng/mL)
      in hepatitis B surface antigen (HBsAg)-positive recipients was attempted at 6
      months after transplantation. RESULTS: Graft actuarial survival rates at 1, 5,
      and 10 years posttransplantation were 89%, 75%, and 57%, respectively. Acute
      rejection and increased recipient age were found to be significant risk factors
      (p < 0.05) affecting graft survival, with hazard ratios of 5.20 and 1.74,
      respectively, by multivariate analysis using a Cox proportional hazards model.
      Hepatitis B and/or hepatitis C infection had no influence on graft survival.
      CONCLUSIONS: In this series of cadaveric renal allograft patients, the risk
      factors affecting allograft survival were acute rejection and recipient age.

PMID- 10925551
TI  - Percutaneous epididymal sperm aspiration versus microsurgical epididymal sperm
      aspiration for irreparable obstructive azoospermia--experience with 100 cases.
AB  - PURPOSE: This study investigated the sperm retrieval success rates, fertilization
      rates, pregnancy rates, and complications of percutaneous epididymal sperm
      aspiration (PESA) and microsurgical epididymal sperm aspiration (MESA) in cases
      of irreparable obstructive azoospermia. METHODS: During a period of 36 months,
      100 men with irreparable obstructive azoospermia underwent 109 cycles of sperm
      retrieval procedures and intracytoplasmic sperm injection (ICSI). We routinely
      performed PESA first in each retrieval cycle; MESA and/or testicular sperm
      extraction (TESE) were performed if PESA failed. The sperm retrieval success
      rates, mean fertilization rates, and pregnancy rates of PESA and MESA were
      evaluated. RESULTS: PESA was performed in all 109 retrieval cycles with a
      successful sperm retrieval rate of 61%. When PESA failed to retrieve a sufficient
      number of viable sperm, MESA was subsequently performed with a sperm retrieval
      rate of 93%. Three cases, which had failed retrieval with both the PESA and MESA
      procedures, received TESE successfully. The rates of fertilization and pregnancy
      were 56% and 39% in the 66 PESA-ICSI cycles, respectively, and 47% and 45% in the
      40 MESA-ICSI cycles. No significant differences were found in fertilization rates
      or pregnancy rates among the various sperm retrieval methods and obstruction
      etiologies. The overall mean fertilization rate and pregnancy rate were 51% and
      41%, respectively. CONCLUSION: Both PESA and MESA can be used successfully to
      obtain sufficient sperm for ICSI. PESA cannot replace MESA in some cases as some
      epididymal pathologies prevent its success. The results of this study indicate
      that PESA should be the treatment of choice for patients with ductal obstruction
      distal to the epididymis, owing to its higher initial success rate. In contrast,
      patients with irreparable epididymal obstruction might achieve better success
      rates with MESA.

PMID- 10925552
TI  - Thermographic study of palmar and facial skin temperature of hyperhidrosis
      patients before and after thoracic sympathectomy.
AB  - PURPOSE: The purpose of this study was to investigate the roles of the second
      thoracic sympathetic segment in the sympathetic innervation of the hands and
      face, and to compare skin temperature changes in the palms, fingers, face, and
      neck of palmar hyperhidrosis (PH) patients before and after endoscopic thoracic
      sympathectomy. METHODS: Twenty-two patients, 14 women and eight men, with severe
      PH were treated with endoscopic ablation of the T2 segment. The skin temperatures
      of the hands, neck, and face were assessed by infrared thermography both before
      and after operation. RESULTS: All obtained satisfactory relief of PH. Before
      sympathectomy, thermography revealed that the palmar skin temperature (PST) was
      significantly lower than the facial temperature by 1.3 degrees C (paired t-test,
      p < 0.005). After sympathectomy, thermography showed significant elevations in
      temperature mainly of the thenars, palms, digits, and nose, but not of the
      forehead, mandible, or neck (ANOVA, p < 0.05 with Bonferroni t-test). The
      variations in PST among PH patients were much greater preoperatively than
      postoperatively. More prominent postoperative PST elevation was found in PH
      patients with lower preoperative PST (r = 0.898, p < 0.001). CONCLUSIONS: These
      findings demonstrate that the T2 segment is the key source of sympathetic
      innervation to the hand and that the T2 segment contributes only trivial
      sympathetic innervation to the face. The results of the present thermography
      studies offer descriptive information about the autonomic innervation of the
      upper thoracic sympathetic trunk.

PMID- 10925553
TI  - Modified Bankart procedure for recurrent anterior shoulder dislocation.
AB  - BACKGROUND AND PURPOSE: Recurrent anterior shoulder dislocation is a serious
      condition, for which the Bankart procedure is a standard treatment. Having made
      three modifications to the original procedure, we examined the efficacy of this
      modified Bankart procedure in the treatment of patients with recurrent anterior
      shoulder dislocation. PATIENTS AND METHODS: The medical records of 21 patients
      who received a modified Bankart procedure for recurrent anterior shoulder
      dislocation during the period from 1989 through 1998 were retrospectively
      analyzed. The average age at initial dislocation was 22 +/- 5 years. The average
      postoperative follow-up period was 41 +/- 16 months. Three of the patients
      complained of mild shoulder pain before their operation. RESULTS: The
      postoperative loss of external rotation and abduction compared with the
      nonoperated side was 9 +/- 4 degrees and 5 +/- 4 degrees, respectively. There
      were no limitations in daily activities during follow-up. No patient had shoulder
      pain after surgery. Redislocation occurred in one patient during the follow-up
      period. Patient satisfaction was rated as excellent by 20 (96%) patients and poor
      by one. CONCLUSION: This modified Bankart procedure is a technically easy
      operation with a low complication rate, a high rate of patient satisfaction, and
      a low redislocation rate. It is a procedure of choice for the management of
      traumatic recurrent anterior shoulder dislocation.

PMID- 10925554
TI  - Gender differences in the patterns of coronary angiography and PTCA use in a
      university hospital in Taiwan.
AB  - BACKGROUND AND PURPOSE: Coronary artery angiography (CAG) and percutaneous
      transluminal coronary angioplasty (PTCA) are important procedures for the
      diagnosis and treatment of patients with coronary artery disease. However, long
      term trends in the frequency of CAG and PTCA use and their relation to gender
      have not been clearly determined in the Asian population. The purpose of this
      study was to investigate gender differences in the patterns of CAG and PTCA use
      in a university hospital in Taiwan during the period of 1983 through 1996.
      METHODS: We studied the monthly data of all patients who underwent CAG or PTCA in
      a university hospital in Taipei from 1983 through 1996. A time series analysis
      was used to estimate gender differences in the patterns of CAG and PTCA use.
      RESULTS: The frequency of CAG and PTCA increased significantly during this
      period. Before 1990, only a small number of patients underwent PTCA. However,
      this number increased steadily after 1990. Men were more likely to undergo CAG
      and PTCA than women. A time series analysis with fitted models was used to create
      an integrated moving average model. For CAG, the value of the estimated intercept
      for men was 2.5 times greater than that for women. In the PTCA series, the value
      of the intercept in men was 4.4 times greater than that in women. The patterns of
      trend change showed greater increases in men than in women, and a greater
      increase in the PTCA than in the CAG series. By transfer function modeling and
      intervention analysis, we found that the effect of CAG on the frequency of PTCA
      in men was 1.8 times greater than its effect in women. The estimated influence of
      the use of a new catheterization room (added in 1993) was 2.8 times greater in
      men than in women. The fitted model correlated well with the observed values in
      the next 12 months for both genders. CONCLUSIONS: We concluded that women had
      fewer CAG and PTCA procedures than men, and the influence of CAG on the PTCA
      series was significantly higher in men than in women.

PMID- 10925555
TI  - Efficiency and effectiveness of stroke rehabilitation after first stroke.
AB  - PURPOSE: To investigate predictive variables of rehabilitation efficiency and
      achievement of rehabilitation potential following stroke rehabilitation. METHODS:
      We prospectively studied 110 first-stroke patients consecutively admitted to the
      inpatient rehabilitation department of our university hospital from 1 January to
      31 December 1997. Functional recovery was measured as improvement in the ability
      to perform the Functional Independence Measure (FIM) instrument. Major medical
      (side of paralysis, stroke etiology, risk factors, Brunnstrom motor recovery
      stage, etc.), rehabilitative (initial FIM subscore, interval from stroke onset to
      rehabilitation commencement, rehabilitation stay, etc.), and demographic (age,
      years of education, occupation, marital and living status, care-giver, etc.)
      variables were examined. RESULTS: The mean FIM score was 57.7 +/- 24.5 at
      admission and 77.3 +/- 26.3 at discharge. The mean rehabilitation efficiency (0.7
      +/- 0.7) and effectiveness (30.6 +/- 24.0%) of stroke rehabilitation were
      determined. Rehabilitation efficiency and rehabilitation effectiveness were
      significantly predicted by length of stay and arm motor recovery stage, and by
      age and arm motor recovery stage, respectively. The variance explained only 21%
      of the rehabilitation efficiency and 24% of the achievement of rehabilitation
      potential. CONCLUSIONS: The results of this study suggest that the large
      proportion of the unexplained variance in rehabilitation efficiency and
      effectiveness is due to nonmedical factors influencing the selection of patients
      for rehabilitation.

PMID- 10925556
TI  - Effects of bombesin on gut mucosal immunity in rats after thermal injury.
AB  - BACKGROUND AND PURPOSE: Severe burns induce a disruption in gastrointestinal
      mucosal integrity and facilitate bacterial translocation (BT). Bombesin (BBS), a
      tetradecapeptide analogous to mammalian gastrin-releasing peptide, can induce the
      release of all gut hormones except secretin. This study examined the effects of
      BBS on mucosal immunity in rats after thermal injury. METHODS: Forty-two Sprague
      Dawley rats were divided into one sham control group and six burn groups. Burn
      groups were subjected to 35% total body surface area burn injury. One to 6 days
      after the injury, six animals (one from each group) were killed every 24 hours.
      Biliary secretory immunoglobulin A (SIgA), jejunal mucosal height, intestinal
      permeability, and BT to the mesenteric lymph nodes (MLNs), liver, and spleen were
      examined. In a second experiment, three groups of rats (6 in each) received
      either sham treatment and saline injection, or thermal injury and saline
      injection, or thermal injury and BBS injection. Twenty-four hours after burns or
      sham treatment, six animals (1 from each group) were killed. The biliary SIgA,
      jejunal mucosal height, and BT to the MLNs, liver, and spleen were examined.
      RESULTS: The biliary SIgA decreased to one-seventh of normal levels 1 day after
      burn injury, and increased thereafter. The jejunal mucosal height decreased
      significantly to two-thirds of the normal value 1 day after burn injury. The
      intestinal mucosal permeability increased significantly to three times the normal
      level 2 days after the burn injury, and decreased thereafter. BBA significantly
      reduced the BT incidence and significantly increased the biliary SIgA and jejunal
      mucosal height 1 day after burn injury. CONCLUSIONS: The results of this study
      show that, in rats, the intestinal permeability increased, the gut mucosal
      barrier failed, and the gut immunity deteriorated in the first few days after
      burn injury. BBS therapy helped to restore the postburn gut mucosal barrier in
      rats, by increasing biliary SIgA levels and the jejunal mucosal height.

PMID- 10925557
TI  - Bone marrow transplantation from an HLA-matched unrelated donor for treatment of
      Chediak-Higashi syndrome.
AB  - Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease
      characterized by partial albinism and large granules in all granule-containing
      cells. It is also associated with recurrent pyogenic infections secondary to
      impaired leukocyte function. Most patients with CHS enter an accelerated phase
      that leads to repeated infections and bleeding complications, often resulting in
      death. The first accelerated phase may occur shortly after birth or several years
      later. There are no curative treatments, and bone marrow transplantation (BMT) is
      the treatment of choice. Here, we report the case of a boy with CHS. The
      diagnosis was made at the age of 1 month, on the basis of the characteristic
      clinical findings and family history. He received BMT from an HLA-matched
      unrelated donor. After BMT, fluorescent cytometric analysis of polymorphonuclear
      leukocytes showed normalized cellular granularity and a normal increase in CD11b
      expression on N-formylmethionyl-leucyl-phenylalanine stimulation. The accelerated
      phase did not develop during 27 months of follow-up. Without BMT, CHS is usually
      fatal before the age of 10 years. BMT from an unrelated donor may be an effective
      treatment option for those who lack sibling donors. In addition to the
      characteristic leukocytic dysfunctions, fluorescent cytometric analysis of
      cellular granularity and surface molecules offer useful diagnostic information.

PMID- 10925558
TI  - Nephrotic syndrome in a bone marrow transplant recipient without chronic graft
      versus-host disease.
AB  - A 5-year-old girl developed severe proteinuria and microscopic hematuria 17
      months after allogeneic bone marrow transplantation (BMT) for chronic myeloid
      leukemia. These nephrotic symptoms occurred during cyclosporin tapering, in the
      absence of other signs of chronic graft-versus-host disease (GVHD). A renal
      biopsy revealed focal segmental glomerulosclerosis. After methylprednisolone
      therapy, the proteinuria gradually decreased. The altered or disordered immune
      regulation that occurred after BMT may have resulted in the development of
      nephrotic syndrome.

PMID- 10925559
TI  - Complete myocardial revascularization using only pedicled arterial conduits in
      Kawasaki disease.
AB  - A 16-year-old boy with Kawasaki disease suffered from progressive angina and
      exercise intolerance for 1 year. Coronary angiography showed 60% stenosis of the
      left main coronary artery, a calcified aneurysm with total occlusion at the
      proximal left anterior descending artery (LAD), and another aneurysm with total
      occlusion at the middle portion of the right coronary artery. Aortocoronary
      bypass was done with the left internal mammary artery (IMA) anastomosed to the
      first obtuse marginal branch, the right IMA to the distal LAD, and the right
      gastroepiploic artery to the posterior descending artery. Graft patency was
      documented by follow-up coronary angiography 1 month after surgery. During follow
      up, his rapid improvement led to an upgrade from New York Heart Association
      functional class III to class I. The results of the present case suggest that
      complete myocardial revascularization using arterial conduits in patients with
      Kawasaki disease with coronary artery occlusion is safe and effective.

PMID- 10925560
TI  - Mini-laparoscopic reduction of intussusception for children.
AB  - The success of mini-laparoscopic cholecystectomy and splenectomy has encouraged
      the application of this new technique in children with non-complicated
      intussusception. Here, we report on the use of this technique in two children,
      aged 21 and 24 months, respectively, who had failed saline enema reduction of
      ileocolic intussusception. Under a 2-mm videoscopic visualization, the
      intussuscepted bowel was identified and reduced with the assistance of a 2-mm
      working port placed at the right lower abdominal area and a 5- to 10-mm working
      port placed at the supraumbilical area. An intussuscepted lymph node at the
      ileocecal area, as the lead point, was removed at the time of the procedure in
      one child. Both patients experienced relief of symptoms the day after operation
      and resumed a regular diet on the first post-operative day. No recurrence or
      complications, including abscess and wound infection, occurred. These findings
      suggest that mini-laparoscopic reduction is a safe procedure for children with
      uncomplicated intussusception. Moreover, the procedure provides better cosmesis
      than conventional laparoscopic techniques.

PMID- 10925561
TI  - Management of pleural effusions.
AB  - This review summarizes current strategies in the treatment of patients with
      pleural effusion. To determine whether a patient has a transudative or exudative
      pleural effusion, Light's criteria should be applied to measure the
      concentrations of protein and lactate dehydrogenase (LDH) in the pleural fluid
      and serum. If the effusion is transudative, therapy should be directed toward the
      underlying congestive heart failure, cirrhosis, or nephrosis. Consideration
      should be given to pleurodesis with a sclerosant if patients with recurrent
      transudative effusion have severe dyspnea due to their effusion. If the effusion
      is exudative, attempts should be made to define the etiology. The diagnosis of
      pleural malignancy is most easily established via pleural fluid cytology. If this
      is negative and the patient is suspected of having pleural malignancy,
      thoracoscopy is indicated. The concentrations of adenosine deaminase and gamma
      interferon in pleural fluid are useful in the diagnosis of pleural tuberculosis.
      Patients with pneumonia and pleural effusion should undergo therapeutic
      thoracentesis; the pleural fluid should be Gram-stained and cultured, and the
      differential cell count, glucose and LDH concentration, and pH should be
      determined. Indicators of a poor prognosis include the presence of frank pus, a
      positive Gram-stain, a pleural glucose concentration of less than 2.2 mmol/L, a
      pH less than 7.00, the presence of pleural loculations, and an LDH concentration
      greater than three times the upper limit of normal in serum. If the pleural fluid
      cannot be completely evacuated because of loculations, intrapleural thrombolytic
      therapy should be considered. If thrombolytics are ineffective, thoracoscopy or
      thoracotomy with decortication should be performed. Dyspneic patients with
      malignant pleural effusions whose dyspnea is relieved with therapeutic
      thoracentesis should be considered for pleurodesis using a tetracycline
      derivative. Talc is not recommended because it induces acute respiratory distress
      syndrome in about 5% of patients, with an overall mortality of 1%.

PMID- 10925562
TI  - Hospital arrival time after onset of different types of stroke in greater Taipei.
AB  - BACKGROUND AND PURPOSE: The effectiveness of stroke treatment is highly dependent
      on the post-onset time of treatment. Recent reports have established the
      importance of aggressive medical or surgical intervention in the hyperacute
      stage. In order to design an appropriate treatment program for acute stroke
      patients, we studied the arrival time after onset of different types of stroke at
      a tertiary medical center serving the greater Taipei area. METHODS: This was a
      prospective study of acute stroke patients admitted to the emergency department
      (ED) during a 1-year period (1997). There were 842 patients with accurate records
      of hospital arrival time who were either directly or indirectly admitted to the
      ED during the study period. Each stroke patient had a diagnosis of either
      cerebral infarction (CI), cerebral hemorrhage (CH), subarachnoid hemorrhage
      (SAH), or transient ischemic attack (TIA). CI was further divided into five
      subtypes: large artery atherothrombosis, lacunae, cardioembolism, other specific
      causes, and undetermined cause. The arrival time after stroke onset was
      stratified into seven different time intervals: 0 to 3, 3 to 6, 6 to 12, and 12
      to 24 hours, and 1 to 3, 3 to 7, and more than 7 days. RESULTS: Stroke patients
      who came directly to the ED arrived much sooner after onset than those who came
      via an indirect route (80.5% vs 36.5% in the first 24 hours). Of the 617 patients
      in the direct group, the percentage of patients arriving at the ED within 3 hours
      after onset was significantly greater among CH (66.2%), SAH (68.4%), and TIA
      (57.9%) patients than among CI (27.4%) patients. The percentage of CI patients
      who arrived early (0 to 3 hours) was significantly higher in those with
      cardioembolism (56.3%) than in those with large artery atherothrombosis (24.5%),
      lacunae (15.3%), other specific causes (13.6%), or undetermined cause (23.2%).
      CONCLUSIONS: These results show that direct transportation to the ED after stroke
      onset resulted in shorter treatment delay; hospital arrival time varied
      significantly among the different types of stroke and subtypes of CI. Patients
      with hemorrhagic stroke (CH and SAH) and cardioembolism were sent to the ED with
      the shortest delay. These results may be useful in strategic planning for stroke
      management.

PMID- 10925563
TI  - Clinical spectrum of acute respiratory distress syndrome in a tertiary referral
      hospital: etiology, severity, clinical course, and hospital outcome.
AB  - BACKGROUND AND PURPOSE: The clinical picture of patients with acute respiratory
      distress syndrome (ARDS) in Taiwan has seldom been reported, although new
      definitions of ARDS have been introduced over the past years. The purpose of this
      study was to investigate the clinical characteristics, modalities of management,
      and outcomes in patients with ARDS treated in a tertiary referral hospital.
      METHODS: Case records were selected through a computerized search of diagnosis
      codified at discharge during the period from January 1995 to June 1997. Patients
      who met the criteria of the American-European Consensus Conference definition of
      ARDS were included and their medical records were retrospectively reviewed.
      RESULTS: A total of 145 patients (91 men, 54 women; mean age, 58 years) who
      fulfilled the criteria for ARDS were identified. Malignancy (n = 53) and diabetes
      mellitus (n = 23) were the most common co-morbid conditions. Pneumonia (n = 90),
      including community-acquired pneumonia in 45 (31%) patients, was the most common
      risk factor. The lung injury score at the time of ARDS diagnosis was 2.89 +/-
      0.40 (mean +/- standard error, SE). The worst value of PaO2/FIO2 was 86.8 +/- 3.8
      mm Hg (mean +/- SE). Among the 145 patients, 130 (90%) received mechanical
      ventilation and 118 (81%) were treated in the intensive care unit. In-hospital
      mortality was 87%. Seventy (48%) patients received intensive treatment for ARDS,
      among whom 52 (74%) died; the most common causes of death were multiple organ
      failure (54%) and respiratory failure (23%). CONCLUSIONS: The mortality in
      patients with ARDS was high in this tertiary referral institution. Our findings
      suggest that aggressive ventilatory, pharmacologic, and supportive therapy may be
      important to achieve a higher survival rate.

PMID- 10925564
TI  - Clinical features of and risk factors for fungal peritonitis in peritoneal
      dialysis patients.
AB  - BACKGROUND AND PURPOSE: Fungal peritonitis (FP) is a serious complication for
      peritoneal dialysis (PD) patients and can result in technical failure and
      mortality. Catheter removal remains the mainstay of treatment. This study sought
      to identify the risk factors for FP in order to facilitate the prevention of this
      catastrophic complication. METHODS: A total of 246 patients who received long
      term PD from 1985 to 1998 were included in this retrospective study. Twenty
      episodes of FP occurred in 19 patients. The clinical characteristics, pathogens,
      treatment modalities, and outcomes of the FP episodes were retrospectively
      reviewed. The FP incidence in various demographic and clinical groups, classified
      according to sex, age, education, and underlying cause of uremia, were compared
      with the Poisson test. RESULTS: Thirteen episodes of FP were caused by yeast, and
      the remaining episodes were caused by Aspergillus spp. Age, sex, and education
      did not affect the FP incidence. Lupus patients (969 patient-months) had a higher
      incidence of FP than patients with other underlying diseases (p < 0.05). The 19
      FP patients also had a higher incidence of bacterial peritonitis than other PD
      patients (p < 0.01). Among the 20 FP episodes, 14 (70%) were preceded by
      antibiotic use, and eight (40%) developed during hospitalization. Steroids were
      used at the time of FP in five of six lupus patients. Seven patients (37%) died
      within 1 month after diagnosis of FP. Five patients were able to remain on PD
      after FP, but only three patients were able to maintain catheter placement.
      CONCLUSION: The risk factors for FP identified in this study include the use of
      antibiotics and steroids, underlying lupus, frequent occurrence of bacterial
      peritonitis, and hospitalization. Antifungal therapy may allow the catheter to be
      kept in place in a few patients, but catheter removal should be considered in
      patients whose FP is refractory to medical treatment.

PMID- 10925565
TI  - Effects of epidural fentanyl on labor pain during the early period of the first
      stage of induced labor in nulliparous women.
AB  - BACKGROUND AND PURPOSE: It is generally accepted that epidural injection with
      local anesthetics and narcotics administered when the cervix has dilated to a
      diameter exceeding 4 cm can adequately control labor pain. However, many
      nulliparous women still suffer from labor pain for a few hours prior to the
      administration of epidural analgesia. This study examined the effectiveness of
      relief of labor pain obtained by injection of narcotics epidurally once the labor
      pain begins and the subject requests analgesia. METHODS: Subjects scheduled for
      induced labour were divided into three groups: Group A (n = 60) received 5 x 10(
      4)% fentanyl (10-20 mL) administered epidurally to relieve early first-stage
      labor pain. Group B (n = 60) received no analgesic in the early first stage of
      labor. For groups A and B, when cervical dilatation exceeded 4 cm, 10 to 15 mL of
      5 x 10(-2)% bupivacaine and 2 x 10(-4)% fentanyl were injected epidurally and a
      continuous low dosage was maintained until full dilatation of the cervix
      resulted. Group C (n = 198) received no analgesic during the entire labor course.
      RESULTS: There were no significant differences in the duration of the early
      period of the first stage of labor, the duration of the late period of the first
      stage, the duration of the second stage, the Apgar score, or the arterial blood
      gas of neonates among the three groups. However, group C had a significantly
      higher cesarean section rate (28.8%) than group A (16.7%) or group B (15%). Pain
      scores assessed with the Visual Analog Scale (VAS) throughout the entire labor
      course, were lower in group A than in group B; particularly during the early
      period of the first stage. The VAS scores in both groups A and B were
      significantly lower than those in group C during the late period of the first
      stage of labor. CONCLUSIONS: The results indicate that once labor pain begins and
      the subject requests analgesia, epidural injection with fentanyl alone can
      relieve labor pain during the early period of the first stage. The analgesia does
      not cause adverse effects to the mothers or neonates. In addition, the labor
      course and the method of delivery are not affected.

PMID- 10925566
TI  - Effect of magnolol on coronary vascular resistance in rabbits: measurement with
      pulsed Doppler velocimetry.
AB  - BACKGROUND AND PURPOSE: Magnolol is an active component purified from Magnolia
      officinalis that has been reported to protect the myocardium against infarction
      and reperfusion injury. The purpose of this study was to investigate the effect
      of magnolol on the coronary circulation and to determine whether a change in
      coronary vascular resistance could be the mechanism underlying its myocardial
      protective effect. METHODS: Male New Zealand white rabbits were anesthetized. A 3
      mm suction-type pulsed Doppler velocimetry probe was applied to the proximal part
      of the left anterior descending coronary artery after median sternotomy. The 39
      rabbits received intravenous injection of either vehicle (n = 5), magnolol (10(
      6) g/kg, n = 6; 10(-5) g/kg, n = 5; 10(-4) g/kg, n = 5), or nitroglycerin (10(-5)
      g/kg, n = 6; 10(-4) g/kg, n = 6; 10(-3) g/kg, n = 6). The effects of magnolol and
      nitroglycerin on coronary vascular resistance were compared. RESULTS: Magnolol
      did not change blood pressure or coronary blood flow velocity. However, at a dose
      of 10(-4) g/kg, it decreased coronary vascular resistance significantly more than
      vehicle (88 +/- 1% vs 95 +/- 1% of baseline coronary vascular resistance, p <
      0.001). Nitroglycerin increased coronary blood flow velocity and decreased
      coronary vascular resistance in a dose-dependent manner (p < 0.01). CONCLUSIONS:
      Magnolol reduced coronary vascular resistance in anesthetized, open-chest rabbits
      only at a high concentration. Its effect was modest compared with that of
      nitroglycerin. Since magnolol protects the myocardium at relatively low doses,
      coronary vasodilatation is unlikely to be the underlying mechanism responsible
      for its myocardial protective effects.

PMID- 10925567
TI  - Evaluation of optic disc changes in severe myopia.
AB  - PURPOSE: To evaluate the changes in the optic nerve head in highly myopic
      subjects by means of confocal laser scanning opthalmoscope. METHODS: Using laser
      scanning and a three-dimensional image analysis system, we studied 114 young
      (21.4 +/- 1.4 years), highly myopic subjects with refractive errors greater than 
      8.0 D and a control group of 29 subjects (18.9 +/- 1.2 years) with myopia of -3.0
      D or less. Measurements included cycloplegic refraction, corneal curvature,
      biometric axial length, and morphometric values of the optic disc obtained with a
      laser scanning disc analyzer. RESULTS: The optic disc area in highly myopic eyes
      was similar to that in mildly myopic eyes. However, regression analysis revealed
      that the optic disc area increased with axial length in subjects with severe
      myopia. The cup/disc ratio, the disc depth, the neuroretinal rim area, and the
      tilting of the disc were not significantly different between the severe and mild
      myopia groups. CONCLUSIONS: These findings may be useful in further
      investigations of myopic progression and of the mechanisms responsible for the
      development of myopic complications.

PMID- 10925568
TI  - Novel cystic fibrosis mutation (2215insG) in two adolescent Taiwanese siblings.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder that is rarely found in
      Asians. Only four cases of CF from four different families have been reported in
      Taiwan. We report two cases of CF involving two teenage siblings. Both presented
      with repeated airway infections, poor weight gain, clubbing of the fingers,
      hypoxemia, and obstructive ventilatory impairment. Multiple focal bronchiectases
      and emphysema were demonstrated on high-resolution computed tomography. Sweat
      chloride concentrations, as measured using the modified sweat chloride test in a
      closed space with a heater, were 327 mmol/L and 276 mmol/L, respectively. To
      confirm the CF diagnosis, DNA mutation analysis was performed. All 27 exons of
      the CF transmembrane conductance regulator (TR) gene and their flanking intron
      sequences were screened for nucleotide sequence alterations, and the mutations
      were then identified by direct DNA sequence analysis. Both siblings carried 1898
      + 5G-->T; a mutation previously identified in Taiwan. In addition, the mutation
      analysis identified a new single-base-insertion mutation in exon 13 on the second
      CFTR allele of these patients. This mutation, named 2215insG, is expected to
      cause a significant disruption of CFTR function. The 1898 + 5G-->T/2215insG
      genotype is thus consistent with the CF diagnosis. A new missense mutation,
      S895N, in exon 15 of the CFTR gene, which cosegregated with 2215insG, was also
      identified in both of these patients.

PMID- 10925569
TI  - Chronic focal encephalitis (Rasmussen's syndrome) in an adult.
AB  - Chronic focal encephalitis in adults is rare. Here we report a case of chronic
      focal encephalitis with epilepsy in a man. A 53-year-old man was admitted to our
      hospital because of right-sided focal seizures and epilepticus partialis
      continua. Brain imaging studies demonstrated progressive, focal, left cerebral
      atrophy. Prominent degenerative changes including neuronal loss and astrocytic
      gliosis were found on brain biopsy. Although the characteristics were typical of
      Rasmussen's encephalitis, unlike chronic focal encephalitis in children, his
      seizures were easily controlled by traditional antiepileptic therapy.

PMID- 10925570
TI  - Thoracic cord compression due to gout: a case report and literature review.
AB  - An 82-year-old man developed progressive weakness of both legs 1 month prior to
      admission. He reported no previous history of trauma. Spine radiography revealed
      marked thoracic and lumbar spondylosis. Magnetic resonance imaging of the spine
      disclosed segmental stenosis with cord compression at T10-11 due to an extradural
      soft tissue lesion. Based on a diagnosis of thoracic spondylosis with cord
      compression, decompression laminectomy was performed. During the operation,
      fragile chalky-white material was noted over the epidural space, compressing the
      thoracic cord. The granular lesion was meticulously removed until the dura was
      identified and the cord was decompressed. Histologic examination of the surgical
      specimen revealed deposits of needle-like crystals that were consistent with
      monosodium urate, demonstrating that a gouty lesion of the thoracic spine had
      caused the cord compression. The patient had previously experienced several
      attacks of gouty arthritis of his feet. The postoperative serum uric acid
      concentration was 8.5 mg/dL. After surgery, he was treated with benzbromarone 100
      mg per day. He was able to walk 3 months after the operation. A high index of
      suspicion of gouty involvement of the spine is necessary in patients with gout.
      Surgical decompression followed by regular administration of antigout drugs can
      provide satisfactory results.

PMID- 10925572
TI  - Treatment of painful heels using extracorporeal shock wave.
AB  - BACKGROUND AND PURPOSE: Shock wave therapy has been shown to improve many
      tendinopathies at the tendon-bone junction. The purpose of this study was to
      investigate the safety and effectiveness of extracorporeal shock wave therapy for
      the treatment of painful heels. METHODS: Sixty-six patients, including 45 women
      and 21 men with an average age of 47.70 years (range, 19-75 years), were included
      in the study. Each patient received 1,000 impulses of shock waves at a 14-kV
      generator voltage at the affected site under local anesthesia. Twelve patients
      received a second treatment, and two patients received a third treatment.
      RESULTS: Of 58 patients with 6 weeks' follow-up, five (9%) were complaint-free,
      21 (37%) were significantly better, 27 (47%) were slightly better, and five (9%)
      were unchanged. Of 41 patients with 12 weeks' follow-up, 11 (27%) were complaint
      free, 22 (54%) were significantly better, seven (17%) were slightly better, and
      one (2%) was unchanged. The results at 12 weeks were much better than those at 6
      weeks. The effect of shock waves on painful heels continued between 6 and 12
      weeks. Twelve patients who did not respond favorably to the first treatment
      showed significantly better results after a second treatment. Two patients who
      had a third treatment also achieved satisfactory results. There were no device
      related problems or systemic or local complications. CONCLUSIONS: Extracorporeal
      shock wave therapy is a new modality that is safe and effective in the treatment
      of painful heel spurs.

PMID- 10925571
TI  - Control of idiopathic ventricular fibrillation by implantable cardioverter
      defibrillator in a child who survived sudden death.
AB  - Idiopathic ventricular fibrillation (VF) is extremely rare in children who have
      not previously undergone cardiac surgery. Patients resuscitated from idiopathic
      VF remain at risk for recurrence. The use of an implantable cardioverter
      defibrillator (ICD) effectively prevents such recurrences. We report the case of
      a 12-year-old girl who had a history of recurrent syncope and had survived an
      episode of VF. Serial studies after prolonged but successful resuscitation,
      including echocardiography, an electrocardiogram (ECG), and coronary angiography
      failed to reveal abnormal cardiac structures responsible for VF. No abnormal
      conduction pathways or abnormal early or late after depolarization were found on
      electrophysiologic study. The ST segments of the 12-lead ECG remained normal
      after procainamide challenge. The patient underwent ICD implantation 2 weeks
      after admission and syncope did not recur during a follow-up of 14 months. This
      report emphasizes that idiopathic VF may be responsible for syncope in children.
      ICD therapy prevents the recurrence of idiopathic VF and the associated risk of
      sudden death.

PMID- 10925573
TI  - [Antibiotic prophylaxis in gastrointestinal surgery. Peroral preparations are
      often better and cheaper than intravenous prophylaxis].

PMID- 10925574
TI  - [How dangerous are mobile phones?].

PMID- 10925575
TI  - [Schwann cells promote development and repair of nerve cells].
AB  - During early development Schwann cells have trophic effects on neurons with
      outgrowing axons. Later these cells are responsible for myelination and formation
      of nodes of Ranvier in the peripheral nervous system, a developmental process
      with considerable functional significance. In adult nerves, Schwann cells and
      axons cooperate closely. After nerve injuries, axons degenerate while Schwann
      cells proliferate and dedifferentiate. The stimulating effects these cells have
      on axonal regeneration are exploited clinically through the use of nerve grafts
      for repair. Schwann cells are used experimentally to enhance regeneration of
      axons in the central nervous system. Tomorrow this may be used clinically--an
      exciting development.

PMID- 10925577
TI  - [A guide to critical reading of clinical articles].

PMID- 10925576
TI  - [Peroral antibiotic prophylaxis in upper gastrointestinal surgery. A study of
      biological availability].
AB  - Sixteen patients undergoing elective upper gastrointestinal surgery with presumed
      normal gastrointestinal function received peroral trimethoprim-sulfamethoxazole
      (TMP/SMZ 160/800 mg) and metronidazole (2 g) in the morning regardless of what
      time the operation was to be started. The concentration of SMZ in plasma was
      measured before and after the operation. Only 37 per cent of the patients were
      found to have adequate levels of SMZ concentration. Patients with grave obesity
      or malignant disease of the liver, biliary tract or pancreas had concentrations
      below the minimal inhibitory concentrations for species of Enterobacteriacae.
      Peroral antibiotic prophylaxis is therefore not suitable in all types of upper
      gastrointestinal surgery.

PMID- 10925578
TI  - [Significance of Cochrane collaboration for evidence-based medicine].

PMID- 10925579
TI  - [Outreach visit and its effect on clinical practice and benefits for the
      patients. A Cochrane review on outreach visits].

PMID- 10925580
TI  - [Scandinavian guidelines for management of head injuries. Evidence-based
      management of minimal, mild and moderate head injuries].
AB  - The Scandinavian Neurotrauma Committee (SNC) was created by the Scandinavian
      Neurosurgical Society in order to develop evidence-based guidelines for improved
      care of neurotrauma patients. A MEDLINE search identified 475 papers dealing with
      the management of minimal, mild and moderate head injuries. Forty-two studies
      presenting Class II evidence on the initial management of such injuries were
      reviewed, and management guidelines were developed. Implementation of the Head
      Injury Severity Scale is advocated. Patients with Minimal injuries (no loss of
      consciousness (LOC), Glasgow Coma Scale (GCS) score 15) can be safely discharged.
      Routine early computerized tomography (CT) scan is recommended in cases with Mild
      injuries (history of LOC, GCS 14-15) and patients with normal scans may be
      discharged. CT scan and admission is mandatory in Moderate injuries (GCS 9-13).
      All patients with additional risk factors should be scanned and admitted. A flow
      chart for clinical decision making and a Head Injury Instruction card is
      introduced. The SNC suggests guidelines that should be safe and cost-effective
      for the initial management of minimal, mild and moderate head injuries.

PMID- 10925581
TI  - [Medical science, medicine and the Janus face of concept or risk. A conversation
      about the medical profession].

PMID- 10925582
TI  - ["Sound and unsound around the Sound". A congress report on health differences
      between Denmark and Sweden].
AB  - During the past 10 years, researchers on both sides of The Sound in the so-called
      Oresund region have worked together to analyze the causes of the observed
      differences in life expectancy between Denmark and Sweden. The region includes
      Copenhagen and North Zealand and the county of Scania in southern Sweden, with
      Malmo as its largest city. Both Denmark and Sweden held top rankings among OECD
      countries in 1970 regarding life expectancy at birth. In 1990 Denmark had fallen
      to a bottom ranking, while Sweden was still at the top. At a scientific meeting
      in Malmo on January 26-27, 2000, some 60 presentations were made concerning
      differences and similarities in health measures on the two sides of the sound
      which divides the two countries. On the Swedish side, life expectancy is 3-4
      years longer than on the Danish side. Paramount among explanations are higher
      mortality figures due to smoking and alcohol-related diseases on the Danish side,
      both in men and women (most pronounced). Minor contributions to the differences
      are suicides and traffic accidents. Historically, Denmark and Sweden have much in
      common. Until 1658, Scania, the Swedish county to the east of The Sound was part
      of Denmark. During the past 150 years rather impressive cultural differences have
      developed. Smoking prevalence and alcohol consumption are more than twice as high
      on the Danish side of the sound. In coming years, researchers, representatives
      for the health service systems and others will work together in order to prevent
      disease and promote health in the Oresund region. The conference was arranged by
      the Medicon Valley Academy, an EU-supported enterprise seeking to stimulate
      research and development within the health sector in the Oresund region (also
      known as Medicon Valley).

PMID- 10925583
TI  - [Don't let misunderstandings about PET kill the interest in a valuable
      technique].

PMID- 10925584
TI  - [Can the SBU conduct critical scrutiny of the scientific literature?].

PMID- 10925585
TI  - [Pro-ANF--a diagnostic tool after all?].

PMID- 10925586
TI  - [Natriuretic peptides in heart failure in primary health care patients].

PMID- 10925587
TI  - [A comment: Pro-ANF was not the main aspect of our study].

PMID- 10925588
TI  - [With optimal diagnosis of enterovirus infections can Sweden be proclaimed free
      from polio in the long run].

PMID- 10925589
TI  - [Thyroid gland--time for new reference values?].

PMID- 10925590
TI  - [How are we to support the sick and their relatives and how are we to give
      difficult information?].

PMID- 10925591
TI  - [Introduction of the concept of neuropsychiatry is no contribution].

PMID- 10925592
TI  - [American top meeting on "science and technology policy" was mostly a fair].

PMID- 10925593
TI  - [The flesh, the devil and freedom. Editorial by J.D. Vincent, Professor of
      Neurophysiology at the Institut Universitaire de France].

PMID- 10925594
TI  - [Ludwig's angina].
AB  - Ludwig's angina is a rare infectious condition originating in the oropharyngeal
      region, most commonly from the teeth. The principal symptoms consist of cervical
      pain, dyspnea, dysphagia, symmetrical neck swelling and fever. Serious
      complications include respiratory collapses, mediastinitis, pleural empyema,
      pericarditis and pericardial tamponade, and may result in the death of the
      patient. The most useful investigations in patients with suspected Ludwig's
      angina are clinical assessment, a cervico-thoracic CT-scan to determine the
      extent of the lesions, microbiological examination and panoramic radiography to
      detect possible dental focuses of infection. Treatment consists of ensuring
      adequate ventilation by securing the upper airways, broad spectrum antibiotic
      therapy, eradication of the source of infection, and often early surgical
      decompression may be necessary. Rapid diagnosis and appropriate treatment can
      reduce the mortality rate to 10%.

PMID- 10925595
TI  - [Prosthesis-related infections].
AB  - Long-term prosthetic devices are rapidly recovered by host proteins which
      increase bacterial adhesion. The bacteria can also produce extracellular
      polysaccharide material, which in combination of host proteins, produce a
      biofilm. This one decreases the host defense mechanisms, antibiotics penetration
      and efficacy, increasing infectivity of the pathogens. Most often, the device is
      contaminated in the perioperative period by commensal flora. It can also be
      infected by hematogenous seeding or by contiguous infection. Various clinical
      presentations of infected devices are described depending on the type of
      prosthesis, its anatomical localisation and the time elapsed since insertion.
      Postoperative acute sepsis, insidious infectious signs or isolated device
      malfunction without signs of infection have all been described. The prosthetic
      infection rate is low, but when it occurs, the consequences are catastrophic.
      Excepted in some selected cases, the classical treatment combines the removal of
      the prosthesis and a long-term appropriate antibiotic therapy. If infection is
      suspected, it's crucial to establish the diagnosis accurately often by using
      invasive diagnostic methods (CT-scan guided biopsy, etc.) to obtain adequate
      samples which detailed microbiological analysis should be carefully interpreted.

PMID- 10925596
TI  - [Cardiac complications of type 2 diabetes].
AB  - Diabetic patients have a higher prevalence of hypertension, dyslipidemia and
      obesity. However, diabetes is by itself a major independent risk factor for
      cardiovascular disease. About two-thirds of total mortality are due to diabetic
      macroangiopathy. It is characterised by accelerated atherosclerosis, with more
      severe, more extensive and more diffuse lesions, as compared with nondiabetic
      patients. Patients with diabetes present more frequently acute pulmonary oedema
      despite similar infarct sizes than do nondiabetic patients. They are more
      frequently at risk for ventricular dysfunction, for ventricular aneurysm and for
      congestive heart failure. At the time of diagnosis of type 2 diabetes, more than
      50% of patients have pre-existing coronary heart disease, probably related to
      painless ischemia, caused by an autonomic denervation of the heart in diabetic
      patients. International recommendations suggest that all diabetic patients should
      be evaluated at least annually for the development or progression of risk factors
      that would prompt cardiac testing. The standard bicycle exercise test should be
      chosen in an asymptomatic patient with only one other risk factor and with a
      normal resting ECG. For all other diabetic patients, stress echocardiography or
      stress myocardial perfusion imaging should be preferably chosen.

PMID- 10925597
TI  - [Giant cystadenoma of the ovary in an adolescent: clinical case and review of the
      literature].
AB  - We report a case of a young adolescent girl presenting a giant ovarian cyst. We
      believe that this is one of the biggest ovarian cysts reported in the literature
      until now. About this observation, a literature review concerning diagnosis and
      treatment of ovarian mucinous cystadenoma in the young girl is done.

PMID- 10925598
TI  - [Serotonin syndrome secondary to the use of sertraline and metoclopramide].
AB  - The authors report the case of a patient who developed a serotonin syndrome after
      taking sertraline and metoclopramide. The symptoms included malaise, cardiac
      arrhythmia, sudation, hyperreflexia, sialosis, diarrhea and were improved by
      cyproheptadine. The authors review the physiological bases of the serotonin
      syndrome, its incidence, clinical manifestations and treatment.

PMID- 10925599
TI  - [Bilateral breast masses].
AB  - A 76 year old woman is hospitalized for bilateral breast masses and neurological
      impairment. Her medical history is marked by rheumatoid arthritis treated with
      gold salts and methylprednisolone. Blood tests reveal pancytopenia; the MRI scan
      of the brain is suggestive of a CNS lymphoma. The pathologic examination of a
      breast mass specimen confirms the lymphoid nature of the neoplasm. This case
      report highlights the multifocal or systemic nature of non hodgkin's lymphoma and
      the diagnostic pitfalls of breast lymphomas. Rheumatoid arthritis and its medical
      management are reviewed for their possible roles in oncogenesis.

PMID- 10925600
TI  - [Comparison of angiotensin receptor antagonists and angiotensin converting enzyme
      inhibitors in arterial hypertension].
AB  - By blocking the renin-angiotensin system, angiotensin converting enzyme
      inhibitors and more recently introduced angiotensin II receptor antagonists are
      two important classes of antihypertensive drugs. Whether one class is superior to
      the other is presently unknown. Their antihypertensive efficacy is comparable.
      Angiotensin II receptor antagonists are particularly well tolerated but the
      converting enzyme inhibitors have broader indications. The results of the large
      studies with morbidity and mortality end-points are awaited to better define the
      place of the angiotensin II antagonists in monotherapy and in combination.

PMID- 10925601
TI  - [The edemas. Nephrotic syndrome].

PMID- 10925602
TI  - [Idiopathic edema].

PMID- 10925603
TI  - [Albert Hustin (1882-1967) and the first blood transfusion].

PMID- 10925604
TI  - [The emphasis on psychiatry in primary health care--a house without foundation
      wall?].

PMID- 10925605
TI  - [The authorship criteria are changed].

PMID- 10925606
TI  - [Oral anticoagulation--a good prophylaxis requiring check up].

PMID- 10925607
TI  - [Boxing: reprehensible--and fascinating].

PMID- 10925608
TI  - [Big fetus--big problems?].

PMID- 10925609
TI  - [Large fetus--a retrospective study].
AB  - BACKGROUND: Large foetus is associated with increased risk of complications
      during labour and delivery. MATERIAL AND METHODS: Data on deliveries and outcome
      of 504 macrosomic newborns (> or = 4,500 g) born 1995-97 at Rogaland Central
      Hospital, Norway. RESULTS: 74% of the mothers were multiparae. Mean weight
      increase during pregnancy was 17.6 kg. In 76% of the pregnancies delivery
      occurred after term. There were large margins of error both in terms of
      measurement of fundal height and after estimation with ultrasound. 12% of the
      newborns had shoulder dystocia. Six children were diagnosed with a brachial
      plexus injury; three injuries were still present three months after birth.
      Induction of labour did not increase the Apgar score or diminish the frequency of
      shoulder dystocia, but it did increase the frequency of operative deliveries and
      transfer to the neonatal unit. INTERPRETATION: The study confirms that large
      foetus is associated with risk of complications.

PMID- 10925610
TI  - [Time delay in the thrombolytic treatment of myocardial infarction].
AB  - INTRODUCTION: Thrombolytic treatment is central in the treatment of patients with
      myocardial infarction. MATERIAL AND METHODS: A cross-sectional study was
      conducted to determine the time delay incurred in thrombolytic treatment of
      patients with myocardial infarction in Ostfold Hospital, Fredrikstad, Norway.
      Over a seven-month period, 317 patients were diagnosed as having myocardial
      infarction. 80 patients (25%) received thrombolytic therapy, 68 of whom (85%)
      were eligible for the study. 12 patients were excluded either because of not
      meeting the inclusion criteria or because of incomplete data. RESULTS: The
      following median times were recorded: from onset of chest pain till first contact
      with the health care services, 59 minutes; from first contact till arrival at
      hospital, 32 minutes; from hospital arrival till initiation of treatment, 40
      minutes; from onset of chest pain till initiation of treatment, 147 minutes. 38%
      of the patients received thrombolysis within 120 minutes of pain onset, and 35%
      received treatment within 30 minutes of arrival in hospital. There was no
      difference in time delay before contacting health care services among patients
      with or without a previous history of coronary heart disease, except for those
      who took nitroglycerine at onset of symptoms. They had the longest time delay.
      INTERPRETATION: In order to reduce time delay, doctors should give better
      instructions to patients with a previous history of coronary heart disease and
      conduct regular training programmes for hospital interns and nurses. It is
      further assumed that prehospital ECG and direct admission to the coronary care
      unit, or initiation of thrombolysis in the emergency department or in the
      ambulance, would result in a considerable reduction in time delay.

PMID- 10925611
TI  - [Rewarming of patients with accidental hypothermia with the help of heart-lung
      machine].
AB  - BACKGROUND: Different techniques have been used for treatment of victims with
      accidental hypothermia. We have used cardiopulmonary bypass (CPB) for rewarming
      hypothermic patients with circulatory failure or cardiac arrest. This report
      summarises our experiences with this patient group. MATERIAL AND METHODS: 23
      patients, submersions (n = 15), avalanche (n = 1) and primary hypothermia
      (immersion/air cooling) (n = 7), were rewarmed using extracorporeal circulation
      with standard equipment for open-heart surgery. RESULTS: On a clinical basis, two
      patient populations could be identified; one group for whom asphyxia was probably
      present prior to and during cooling, and another group for whom asphyxia was
      unlikely. In the first group, one of 13 patients survived compared to the latter
      group where six out of ten survived. A search for laboratory and other variables
      that with certainty could contribute to the prediction of prognosis was
      unsuccessful. INTERPRETATION: Due to lack of safe prognostic predictors, all
      accidental hypothermic victims with circulatory failure should be rewarmed by
      cardiopulmonary bypass before further therapeutic decisions are made.

PMID- 10925613
TI  - [Laminectomy for degenerative spinal stenosis].
AB  - BACKGROUND: Our aim was to find quality indicators like frequency of
      complications and reoperations in addition to post-operative status and patient
      satisfaction. MATERIAL AND METHODS: 57 patients underwent a follow-up after 5.8
      years on average. Most were female and mean age at operation was 60.8 years.
      Information was obtained from patient records and questionnaires returned by
      88.7% of 53 remaining patients. RESULTS: The perioperative complication rate was
      15.8%. Most were light and there was no mortality. Six out of ten patients were
      satisfied, whereas one of three was not. One out of eight regretted the
      procedure. Postoperatively three out of five reported a persistent but usually
      light back problem; the majority of these patients were satisfied. One out of
      four had changed to less strenuous work; near half of the patients had qualified
      for a permanent disability pension. Three patients had been reoperated.
      INTERPRETATION: Our results compare well with other studies, which are reported
      and briefly discussed.

PMID- 10925612
TI  - [UV-B comb versus betamethasone solution in scalp psoriasis].
AB  - BACKGROUND: The aim of the study was to assess the effectiveness of a UV-B-comb
      on scalp psoriasis versus betamethasone valerate solution. MATERIAL AND METHODS:
      Of 44 adult patients with scalp psoriasis, 22 were treated with a dermalight 80
      psoracomb and 22 with betamethasone valerate solution, five times a week for
      three weeks. RESULTS: No difference in effect was found at the end of treatment.
      Two weeks after end of treatment a higher proportion of patients treated with UV
      B-comb (7/22) had remained in remission than those treated with betamethasone
      valerate solution (3/22; p < 0.05). INTERPRETATION: Treatment with a UV-B-comb
      offers a good alternative to topical corticosteroids for patients with scalp
      psoriasis.

PMID- 10925614
TI  - [Troponins and other biochemical cardiac markers--time for a change].
AB  - BACKGROUND: During the last ten years new, more sensitive and specific cardiac
      markers in blood for detection of acute myocardial injuries have been
      characterised and clinically evaluated. Of practical importance is also the fact
      that rapid and robust methods and equipments suitable for emergency service have
      been developed. MATERIAL AND METHODS: Based on literature study and on own
      experiences we give a survey of the most promising cardiac markers with emphasis
      on the troponin T and troponin I. RESULTS: Methodological and pathobiochemical
      aspects are discussed. The diagnostic characteristics and advantages of the new
      markers are in focus, especially with respect to early detection of acute
      myocardial injuries. Finally, we discuss their potential use for stratification
      of patients with acute coronary syndromes with respect to optimal treatment,
      resource-saving monitoring, and more precise prognostication. INTERPRETATION: It
      is recommended that one of the troponins, either I or T, should be included in
      the diagnostic regime for detecting acute coronary syndromes in Norwegian
      hospitals. CKMB, determined as mass and not as activity, ought to be retained, at
      least until more clinical experience with the troponins have been gained by the
      hospital. Myoglobin may only be of interest if early exclusion of myocardial
      injuries has practical consequences. In this connection the transaminases and LDH
      are no longer of any interest.

PMID- 10925615
TI  - [Radiotherapy of skeletal metastases].
AB  - INTRODUCTION: Patients with skeletal metastases represent a large cohort in
      clinical oncology, and the single most frequent indication for palliative
      radiotherapy. Patients with cancer of the breast, lung, prostate and those with
      myelomatosis, constitute approximately 80% of this group. MATERIAL AND METHODS:
      This paper summarizes data from relevant published clinical trials employing
      external irradiation for painful skeletal metastases. More recent randomised
      trials support the view that a single radiation dose of 8-10 Gy is equally
      efficient as ten treatments of 3 Gy delivered over two weeks. However, some still
      believe that fractioned regimes to a higher total dose provide better pain relief
      of a longer duration than a single fraction. RESULTS: We review the current
      diagnosis and treatment of patients with skeletal metastases and discuss some
      aspect of tumour biology. The etiology of pain and the pathogenesis of tumour
      cells affecting bone tissue, resulting in osteolysis and/or osteosclerosis, are
      discussed. Associated leukocyte-derived osteoclast-activating cytokines that
      stimulate pain receptors locally, can in part explain why radiotherapy gives such
      rapid pain relief. INTERPRETATION: The aims of radiotherapy must be assessed in
      relation to the life expectancy of the patient. Based on actual publications and
      own experiences, we suggest treatment with 8 Gy x 1 for the majority of patients,
      and reserve 3 Gy x 10 for patients with longer life expectancy. Both regimes
      allow retreatment, if and when pain eventually reoccur in previously irradiated
      areas.

PMID- 10925616
TI  - [New diagnostic criteria for diabetes mellitus--why?].
AB  - In 1997, the diagnostic criteria for diabetes mellitus were changed in the USA;
      the WHO has also proposed changes in its criteria. The main difference from the
      previous set of WHo criteria is a lowering of the cut-off level of fasting plasma
      glucose to > or = 7.0 mmol/l. This article discusses the implications of new
      diagnostic criteria and recommends that the level of fasting plasma glucose for
      diagnosing diabetes is decreased to > or = 7.0 mmol/l in Norway as well.

PMID- 10925617
TI  - [Fetus with hydrops in a woman from Vietnam].

PMID- 10925618
TI  - [Migraine patients and oral contraceptives].

PMID- 10925619
TI  - [Is the Internet of any help for persons with serious mental disorders?].
AB  - BACKGROUND: Information and communication technology may represent unique
      opportunities as well as challenges for persons who are socially isolated due to
      serious mental disorders. MATERIAL AND METHODS: In order to explore how such
      persons use and experience Internet technology, a pilot project was conducted in
      collaboration with eight subjects. These accepted a PC with Internet access in
      their homes for a period of one year. The experiences reported are based on self
      reports, and observations made by clinical and project personnel. RESULTS: Three
      of the eight subjects reported little or no use of the Internet. For the five
      active users, Internet opened up for social contact and support without provoking
      the same degree of social anxiety as face-to-face interaction. Four of the five
      subjects wish to use e-mail contact as a supplement to face-to-face contact with
      their therapist. INTERPRETATION: Internet can represent a lifeline to society for
      persons isolated due to mental disorders. Electronic based interaction between
      patients and health care professionals will provide unique opportunities as well
      as challenges in efforts towards improving the quality of and access to health
      care services.

PMID- 10925620
TI  - [Teledermatology--experiences from Northern Norway].
AB  - BACKGROUND: Distant diagnosing by two-way interactive motion video
      (videoconference) appeared in the 1980s, the last four years with weekly
      teleconsultations to Hammerfest and Kirkenes. MATERIAL AND METHODS: Patients are
      mostly referred from general practitioners. A physician with a 20% position is
      responsible for organising the videoconferences and participates in the
      consultation. A close-up camera is used for detailed examination of skin lesions.
      Photographs of skin areas may be transmitted directly to the specialist screen
      (still images). The studio physician writes prescriptions and sick leave notes.
      The specialist writes a reply to the referring physician. Referrals using still
      images are as yet at a pilot stage. RESULTS: Patients view early diagnosis, time
      saved, reduced costs, and less need for leave from work as important advantages
      with videoconferences. Patient satisfaction is high, although 10% are
      dissatisfied. Having a physician in the studio makes patients feel safer, and
      they understand the specialist better. This is a new role for the specialist; the
      doctor/patient relationship is often taken care of by the studio physician.
      Comparisons between videoconference and face-to-face consultations have shown up
      to 90% diagnostic agreement. A pilot study using still image referrals showed
      similar results. INTERPRETATION: Videoconferences are well suited in everyday
      dermatology, when follow-up by specialist is necessary, and for patients in
      regular treatment at local clinics for skin disease. Still image referral seems
      promising. The studio physician's diagnostic abilities are enhanced. Many
      patients are not suited for teleconsultation, but telemedical solutions will have
      a role in the years to come.

PMID- 10925621
TI  - [Experiences with teleradiology in general practice in Oppland].
AB  - BACKGROUND: Our aim was to evaluate one year of operation of a newly established
      teleradiology service for people in Mid- and North Gudbrandsdalen (30,000
      inhabitants). In Otta, one radiographer works with digital pictures (phosphorus
      plate technology). Pictures are sent to the local hospital in Lillehammer (115
      kilometres away) by a broadband network (for health services only) for
      radiological evaluation. MATERIAL AND METHODS: We have measured the scope of the
      service, patient satisfaction, management stability and efficiency, and financial
      aspects (the latter are not included in this article). RESULTS: Over one year we
      have examined 3,081 persons (skeleton, thorax, sinuses). A majority of patients
      (90%) thought it was better for them to be examined at Otta. Waiting time was
      short, rarely more than one week. No re-examinations due to insufficient picture
      quality were required. Some expected and some unexpected problems occurred.
      Pictures from 37 patients were lost and could not be radiologically evaluated.
      The lead time from when pictures were taken to when the requisitioning doctor
      received the report, was too long (one to three weeks). The digital pictures are
      not easily available to hospital physicians. Copies must be made on film.
      INTERPRETATION: Our experience is positive. Most problems will be solved by
      storing copies at Otta, by better organisation of the radiologic service, and by
      establishing a digital picture archiving and communication system (PACS) at the
      hospital.

PMID- 10925622
TI  - [Use of information technology in quality development of diabetic care].

PMID- 10925623
TI  - [Why is cardiovascular mortality declining?].

PMID- 10925624
TI  - [What are we supposed to do with more handling programs?].

PMID- 10925625
TI  - [On radiology and radiologic method--cooperation between clinician and
      radiologist].

PMID- 10925626
TI  - [A virus in the vestibular nerve].

PMID- 10925627
TI  - [The basis of psychiatric treatment--from belief to science].

PMID- 10925629
TI  - [Terminal care, not life help].

PMID- 10925628
TI  - [Screening for ovarian cancer].

PMID- 10925630
TI  - [Prevention of ischemic heart disease by changing diet and anticholesteremic
      agents. Risk hysteria or evidence-based work of physicians?].

PMID- 10925632
TI  - [Economic aspects of implementation of the mechanical heart, "HeartMate"].
AB  - This economic evaluation was performed to assess the economic consequences for
      society and for the Danish health care sector of replacing the traditional
      treatment with Biomedicus assist device with The Mechanical Heart, HeartMate, as
      a bridge to transplantation for patients with severe cardiac failure. A cost
      effectiveness analysis showed that the use of HeartMate is more cost-effective
      than the use of Biomedicus assist device. Using HeartMate one life-year gained
      costs DKK 225,000. Using Biomedicus one life-year gained costs DKK 270,000. The
      use of HeartMate results in an additional expenditure of DKK 615,000 per patient.
      By this additional expenditure the patients gain 3.6 extra life-years on average.
      The marginal expenditure by replacing the Biomedicus treatment with HeartMate is
      DKK 170,000 per extra life-year gained.

PMID- 10925631
TI  - [Circulatory support with the mechanical heart, "HeartMate"].
AB  - Treatment with the mechanical heart, HeartMate, has been introduced in Denmark.
      Short-term circulatory support can be obtained by intraaortic balloon
      counterpulsation, an external centrifugal pump and the total artificial heart.
      Long-term circulatory support can be established by treatment with the HeartMate.
      The principle of the mechanical heart is simple--a pump is implanted in parallel
      to the existing heart and connected to external, portable batteries. The patient
      quickly improves and is brought in an optimal state for transplantation. A few
      patients have been able to omit the subsequent heart transplantation. The
      patient's own heart improved during the treatment and the native heart functioned
      again after the system was explanted. The main complications during treatment are
      bleeding, infection, thromboembolic events and systemic failure. Permanent, fully
      implantable mechanical circulatory pumps are under development--which may herald
      the beginning of a whole new era for treatment of cardiac failure.

PMID- 10925633
TI  - [Significance of genetic and environmental factors for asthma. A population-based
      study of 11.688 Danish twin pairs].
AB  - The aim of this study was to estimate the relative influence of genetic and
      environmental factors on the aetiology of asthma. The classic twin study design
      was used to analyse data on self-reported asthma obtained by a questionnaire
      mailed to 34,076 individuals, aged 12-41 yrs and originating from the Danish Twin
      Register. The cumulative incidence proportion was 6.2% in the pooled sample. No
      overall sex or zygosity difference was observed. Substantially higher concordance
      rate, odds ratio and correlation for asthma were estimated in monozygotic than
      dizygotic twin pairs. Using biometric modelling, a model including additive
      genetic and non-shared environmental effects provided the best fit to the data.
      According to this model, 73% of the variation in liability to asthma was
      explained by genetic effects. The results emphasize a major genetic component in
      the aetiology of asthma.

PMID- 10925634
TI  - [Acute pancreatitis caused by Ascaris lubricoides].
AB  - Ascaris lumbricoides as the etiology to acute pancreatitis has never been
      described in Denmark, whereas in India it is a common cause. In most cases
      symptoms lead to investigations with high diagnostic sensitivity end specificity.
      Treatment with antihelminthics and ERCP is efficient. A case of a 25 years-old
      pregnant woman with acute pancreatitis caused by Ascaris lumbricoides is
      reported.

PMID- 10925635
TI  - [Granulosa cell tumors in children].
AB  - Juvenile granulosa cell tumours (JGCT) are rare. They may develop in ovarian or
      testicular tissue. In childhood a special histological type called juvenile
      granulosa cell tumour (JGCT) is seen. Four cases are described: Congenital JGCT
      in a child with sex chromosomal abnormity (45 XO/46 XdicYq) and tumour arising
      from immature testicular tissue, JGCT in the testis of a four month old boy, JGCT
      associated with a hypothalmic hamartoma in a 18 month-old girl, and JGCT in an
      eight year-old girl. In all cases the tumours were benign.

PMID- 10925636
TI  - [Preventive bilateral mastectomy--future treatment of women with high risk of
      breast cancer].

PMID- 10925637
TI  - [Screening for lung cancer--are we to use resources for that?].

PMID- 10925638
TI  - [Ticks or bugs?].

PMID- 10925639
TI  - [Diagnosis of Helicobacter pylori infections--how, when and in whom?].
AB  - Recognition of Helicobacter pylori (Hp) as the major cause of peptic ulcer
      disease has profoundly changed treatment and prognosis of this disease. The
      diagnostic tests are invasive (i.e. via the endoscopy) or non-invasive. The
      invasive tests are: urease test, histology, culture and PCR. Non invasive tests
      are: breath test, serology and Hp-antigens in faeces. The performance of the
      tests are almost similar. Sensitivities and specificities usually are > 90%,
      however the sensitivities and specificities of serological tests may be lower.
      Choice of diagnostic test depends on the clinical situation, sensitivity and
      specificity of test and the prevalence of Hp. Patients who should be examined for
      Hp: 1. The peptic ulcer patient who has used ASA/NSAID (urease test). 2. MALT
      lymphoma, (histology). 3: The young (< 45 years) dyspeptic patient with no alarm
      symptoms and not taking NSAID/ASA (breath test). 4. Recurrence of upper dyspepsia
      after former eradication of Hp in peptic ulcer patients (if malignancy is not
      suspected breath test is first choice). 5. Verification of Hp eradication is
      necessary only in patients with MALT-lymphoma (histology) or patients with
      complicated peptic ulcer. Breath test will be the first choice in patients with
      complicated peptic ulcer when endoscopy is not performed. When endoscopy is
      performed, the urease test is the first choice. Diagnosis of Hp status not
      indicated: 1. There is no documentation that Hp eradication is of benefit in
      patients with non organic dyspepsia. Therefore, there is no indication for
      diagnosis of Hp. 2. Although there is some association between Hp positivity and
      chronic active gastritis and carcinoma of the stomach, there is at present no
      indication for diagnosis of Hp, as treatment of the infection has not proved
      effective in reversing atrophy or dysplasia. 3. The relationship between Hp and
      ASA/NSAIDs in peptic ulcer disease is far from clear. There is no indication for
      diagnosis and treatment of the infection prior to treatment with these
      medications. 4. For patients treated with longterm proton pump inhibitors there
      is no indication for diagnosis and treatment.

PMID- 10925640
TI  - [Parasitologic diagnosis. Ascaris lumbricoides].

PMID- 10925641
TI  - [NSAID and development of ulcer. Are there risk differences between the different
      preparations when it comes to the development of upper dyspepsia and ulcer?].

PMID- 10925642
TI  - [Mushrooms--not always a happy acquaintance].

PMID- 10925643
TI  - [Distal fractures of the femur].

PMID- 10925644
TI  - [Distal fractures of the femur].
AB  - Supracondylar femoral fractures still present a challenge to the treating
      surgeon. The incidence of delayed and non-unions is reduced due to the minimally
      invasive plating techniques, but establishing a correct axis and good function is
      still a problem. During the last few years new implants have been developed to
      allow less difficult operative techniques in minimally invasive surgery. The Less
      Invasive Stabilization System (LISS) is a percutaneous plating system with
      monocortical self-drilling screws. The screws are inserted with an aiming guide
      and form a stable angle with the plate. The distal femoral nail allows placement
      of a spiral blade in the nail, thereby enhancing the interlocking stability.

PMID- 10925645
TI  - [Treatment results after primary and secondary resection of the radial head].
AB  - Apart from comminuted fractures of the radial head the indication for resection
      of the radial head is discussed controversially. To evaluate our own results, the
      hospital notes of 113 patients treated between 1.1.1984-31.12.1994 in our clinic
      by posttraumatic primary or secondary radial head resection were examined
      retrospectively. 79 patients were controlled by clinical and radiological
      examination with an average follow-up of 37.8 months. We examined at 46 patients
      the influence of additional lesions of the elbow joint on the functional outcome.
      In 33 patients follow up was done with special regard to the time of resection.
      Poor results due to the score from Radian and Riseborough especially followed
      secondary radial head resection (> 14 days after trauma) and in case of
      additional elbow lesions. We could not observe problems of the wrist joint after
      radial head resection as described by other authors. According to our own
      experience primary resection is recommended in case of doubtful reconstruction of
      the radial head. In these fracture types radial head resection should not be seen
      as an alternative treatment because of the worse results following secondary
      resection.

PMID- 10925646
TI  - [Treatment of per- and subtrochanteric femoral fractures by gamma nails and
      modular hip prostheses. Differential indications and results].
AB  - From January 1997 to August 1998 all stable and nonstable trochanteric femoral
      fractures (n = 72) were treated routinely by gamma nail using the correct
      operative technique. Patients showing additional osteoarthritis of the hip in
      radiographs hip replacement was performed by a cementless modular femoral hip
      prostheses from January 1996 to August 1998 (n = 28). Follow up period was 6 to
      18 months. Operation time and blood loss were higher using the prostheses.
      However complications and lethality (< 5%) were not different during
      postoperative course. In each group three operative technical complications
      occurred. Using a modified Harris Hip Score (without range of motion,
      contractions) the score was decreased non significant comparing both groups first
      of all in unstable fractures until follow up. In each group one revision
      (loosening of prostheses, excessive shortening of femoral neck) was necessary.
      Using the correct operative technique, the gamma nail proved to be a save device
      with good outcome. Outcome using modular prostheses is comparable to gamma nail.
      Therefore the use of modular prostheses is justified in case of osteoarthrosis
      and in some cases of very unstable fracture.

PMID- 10925647
TI  - [Healing of autologous cancellous bone transplants and hydroxylapatite ceramics
      in tibial segment defects. Value of ultrasonic follow up].
AB  - The aim of this study was to develop and test a scoring system based on real-time
      ultrasonography (US), which is able to predict the healing of a bone defect
      filled with a bone graft substitute or cancellous bone graft. We implanted porous
      hydroxy-apatite (HA) ceramic blocks into a segmental defect in the tibia of 51
      sheep; 14 sheep received autologous bone graft from the iliac crest. Follow-up
      times were 3, 6 and 12 months. With the exception of the 12-month animals, there
      was a minimum of 6 animals in each group. At the end of follow-up the tibiae were
      tested in torsion to failure. These results were correlated with radiographic and
      ultrasound scores measured on the same specimens. With the scoring system it was
      possible to describe the osseous integration of the HA ceramic or mineralisation
      of the cancellous bone graft. Sheep with ceramic implant that developed non
      unions showed a significantly lower score than sheep with a sufficient implant
      integration. A significant correlation between these scores and the biomechanical
      results was found. We were able to define a cut-off within the scoring system
      which made the prediction of instability/non-union possible. In our model we were
      able to predict the osseous integration of HA ceramics and autologous cancellous
      bone grafts with the use of real-time ultrasound.

PMID- 10925648
TI  - [The macroscopic aspect of rotator cuff tears in traumatic and nontraumatic
      rupture cases].
AB  - The decision whether a rotator cuff tear has a traumatic or degenerative origin
      still causes some controversy. Especially in medical expert appraisals the
      etiology of the rotator cuff tear plays an important role referring to insurance
      services for the patient. The purpose of this paper is to compare the
      intraoperative pathomorphologic shape of the cuff tear in traumatic and
      degenerative cases. This study reports of 56 patients with rotator cuff tears
      which were divided in primarily acute, subacute traumatic and degenerative study
      groups referring to their history of present illness. We considered the location
      of the tear, the shape and the size. Furthermore the grade of retraction of the
      supraspinatus tendon, its quality and the shape of the long head of biceps were
      examined. The results showed that in general the shape of the tear gives only in
      some cases significant information whether the etiology is traumatic or not. The
      isolated rupture of the subscapularis muscle and the hematoma at the edge of the
      tendon is significant for the trauma. In comparison with the degenerative study
      group the tenosynovitis and the dislocation of the long head of biceps is in our
      study significant for traumatic tears.

PMID- 10925649
TI  - [Transplant fixation by anterior cruciate ligament reconstruction. Metal vs.
      bioabsorbable polyglyconate interference screw. A prospective randomized study of
      40 patients].
AB  - To overcome some of the potential problems (e.g. hardware removal during revision
      surgery) of metal interference screws used for patellar tendon anterior cruciate
      ligament reconstruction, bioabsorbable screws have recently been introduced.
      Forty patients who underwent endoscopic ACL reconstruction using patella tendon
      autograft were included in the study, they were randomized intraoperatively to
      either Group A (femoral bone block fixation: polyglyconate screw; tibial: metal
      screw) or Group B (both bone blocks fixed with metal interference screws). The
      patients were evaluated clinically preoperatively as well as 6 weeks, 3 months 12
      months and 24 months post op. Lysholm Score at 24 months was 98.1 +/- 2.3 for
      Group A and 97.7 +/- 3.0 for Group B. Tegner Score was 7.4 +/- 1.1 for Group A
      and 7.5 +/- 0.8 for Group B. Two years post op overall IKDC-Score for group A was
      5.6% normal, 88.8% nearly normal and 5.6% abnormal. The result for group B was
      11.1%, 77.8% and 11.1%, respectively. KT-1000 (at 89 N) at two years revealed a
      side to side difference of 1.5 +/- 0.3 mm (Group A) and 1.6 +/- 0.7 (Group B).
      The results of the two groups did not show significant differences at any stage
      of follow up. In our study polyglyconate interference screw fixation for patellar
      tendon grafts has not found to be associated with increased clinical
      complications. It provided equivalent fixation and clinical results compared to
      metal screws.

PMID- 10925650
TI  - [Is a general pharmacologic thromboembolism prophylaxis necessary in ambulatory
      treatment by plaster cast immobilization in lower limb injuries?].
AB  - Selected patients with minor lower limb injuries and low risk for deep vein
      thrombosis (DVT), who required cast immobilizing and did not receive medical
      thrombosis prophylaxis, were included in a prospective study. The decision to
      give not medical thrombosis prophylaxis depended on an concept of individualised
      prophylaxis for patients at risk for thromboembolism. From March 1994 to March
      1996 in 178 outpatients (118 men, 60 women, mean age 25.8 [16-39] years) a
      clinical examination and a colour-coded duplex sonography were performed after
      removal of the cast for detection of DVT of the lower limb. A phlebography was
      performed when thrombosis was suspected. Two patients developed a one bundle
      thrombosis of the calf. Clinical appearance of lung embolism was not observed.
      These results suggest, that low risk patients with minor injuries of the lower
      limb and plaster cast immobilisation do not need a medical thrombosis
      prophylaxis.

PMID- 10925651
TI  - [Benign tenosynovial giant cell tumor in the region of the upper ankle joint. A
      rare differential diagnosis of a soft tissue tumor of the foot].
AB  - The giant cell synovioma is a benign neoplasia classically located in the
      fingers. It mostly rises from tendon sheaths, sometimes from the synovia. Other
      locations than the fingers are rare. Making a differential diagnosis to lipomas,
      gangliomas or even malignant soft tissue tumors can be very difficult especially
      in rare locations. We report the case of a 21 years old man suffering from a
      giant cell synovioma in the area of the right ankle joint. The clinical,
      radiological and patho-morphological findings are documented. The tumor was
      excised totally, other foci were not found. The problems of making the right
      diagnosis are described.

PMID- 10925652
TI  - [Finger and metacarpal fractures. Surgical and nonsurgical treatment procedures.
      I].

PMID- 10925653
TI  - [Lactic acidosis: a complication of spinal cord injury in multiple trauma].
AB  - Large-dose methylprednisolone has been advocated to lessen neurologic deficits in
      spinal cord injury for nearly a decade despite confounding statistical results in
      the Second National Acute Spinal Cord Injury Study (NASCIS-2). Recent
      retrospective studies found lack of significant functional improvement, increases
      in the incidence of infectious complications and an increase in ventilated and
      intensive care days in steroid-treated groups. We report on five cases with
      severe hyperglycemia and nonketotic metabolic acidosis in otherwise non-diabetic
      patients with multiple blunt injuries and an associated spinal cord injury. Those
      adverse effects were induced by epinephrine and aggravated by methylprednisolone.
      We conclude that high-dose methylprednisolone should be avoided in multiple
      injured or otherwise compromised patients potentially needing catecholamine
      support.

PMID- 10925654
TI  - [Calcaneus pseudarthrosis: a clinical rarity].
AB  - The calcaneus pseudoathrosis is rarely seen in clinical workday and we couldn't
      find any case be reported. In two cases the authors present the diagnosis and
      therapy of a non-union after a calcaneus fracture. The authors point especially
      at anatomical characteristics and biomechanical reasons and their meaning for
      aetiology of pseudoathrosis after a calcaneus fracture.

PMID- 10925655
TI  - [Traumatic dislocation of the tibialis posterior tendon].
AB  - Traumatic dislocations of the tibialis posterior tendon are a rare entity
      compared to other injuries of the ankle joint. It should be considered if the
      patient presents with the mechanism of an ankle sprain in combination with severe
      pain in the region of the internal malleolus. We report of two cases of a
      traumatic dislocation of the tibialis posterior tendon and discuss the clinical
      image and the operative treatment.

PMID- 10925656
TI  - [Post-traumatic metatarsalgia. Early results of treatment with a new insole].
AB  - Injuries of the forefoot are a challenge for orthopaedic surgeons. After healing
      of bone and soft tissue damage, posttraumatic metatarsalgia can persist. The
      paper presents a therapy algorithm with newly designed insoles, which consist of
      the common orthopaedic adaptations like a rocker bottom and a stiffening of the
      sole. The therapy is shown on two cases. With these orthotics adequate is
      possible and pain relief realistic.

PMID- 10925657
TI  - [The dilatation technique with the novel trocar 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- 10925658
TI  - [Experience and practical aspects of establishing a quality management system in
      a hospital].

PMID- 10925659
TI  - [The correction of the subcellular postradiation changes in the hypothalamus and
      parathyroid gland by using low-intensity laser radiation (an experimental
      study)].
AB  - The exposure of the rat adrenals 30 days after radiation (1 Gy) to low-intensity
      infrared laser radiation arrests development of ultrastructural disorders in the
      cells of hypothalamus and parathyroid gland, enhances subcellular manifestations
      of adaptation and rehabilitation processes.

PMID- 10925660
TI  - [A comparative analysis of the efficacy of rehabilitative treatment after a
      surgical intervention in ischemic heart disease patients at a rehabilitation
      center and under home conditions].
AB  - Early 12-week combined rehabilitation of IHD patients after surgery enhances
      physical performance, diminishes the damage of IHD risk factors, raises quality
      of life. Physical performance and cardiorespiratory functional reserve improve in
      a greater degree in patients undergoing rehabilitation according to the
      individual program in the rehabilitation center. Home rehabilitation also
      provides positive results but it is less effective.

PMID- 10925661
TI  - [Changes in lipoprotein metabolism during the rehabilitation of ischemic heart
      disease patients after aortocoronary bypass at a health resort in the foothills].
AB  - 284 patients with IHD after coronary artery bypass operation have undergone
      rehabilitation at low-mountain health resort Kislovodsk. The study of lipoprotein
      metabolism has detected a positive trend in this metabolism as shown by lowering
      of blood cholesterol, low density lipoproteins, phospholipids and triglycerides,
      elevated levels of high density lipoproteins.

PMID- 10925662
TI  - [The use of low-frequency magnetotherapy and EHF puncture in the combined
      treatment of arterial hypertension in vibration-induced disease].
AB  - Combination of EHF therapy + magnetotherapy + drugs results in faster and
      persistent hypotensive and analgetic effect compared to standard drug therapy,
      potentiates action of vascular drugs on cerebral and peripheral circulation,
      reduces dose of hypotensive drugs in patients with arterial hypertension and
      vibration disease.

PMID- 10925663
TI  - [The methodological aspects of assessing treatment efficacy at a health resort].
AB  - The paper provides analysis of the existing system of assessing short-term
      results of sanatorium treatment for nonspecific respiratory diseases. It is
      inferred that the system is unsatisfactory and requires revision. Methodological
      approaches are described which could guide in construction of a new system of
      deciding about the effectiveness of sanatorium treatment effectiveness.

PMID- 10925664
TI  - [The effect of different types of weather on external respiratory function in
      children ill with bronchial asthma].
AB  - Questioning of 70 children with bronchial asthma aged 9 to 14 has identified high
      percent (71.4%) of meteolabile patients who respond to unfavourable weather with
      changed function of the external respiration. Reduction of pulmonary ventilation
      led to clinical deterioration.

PMID- 10925665
TI  - [The optimization of an early rehabilitation program for cerebral stroke
      patients: the use of different methods of magneto- and laser therapy].
AB  - Magnetotherapy and laser therapy were used in complex and complex-combined
      regimens in 75 patients after cerebral ischemic or hemorrhagic stroke starting on
      the poststroke week 4-5. Clinico-neurologic, neurophysiological and
      cerebrohemodynamic findings evidence for the highest effectiveness of
      neurorehabilitation including complex magneto-laser therapy in hemispheric
      ischemic and hemorrhagic stroke of subcortical location in the absence of marked
      clinico-tomographic signs of dyscirculatory encephalopathy. Complex-combined
      magneto-laser therapy is more effective for correction of spastic dystonia.
      Mutual potentiation of magnetotherapy and laser therapy results in maximal
      development of collateral circulation and cerebral hemodynamic reserve (84% of
      the patients). Complex effects manifest in arteriodilating and venotonic effects.
      Complex magneto-laser therapy is accompanied by reduction of hyperthrombocythemia
      and hyperfibrinogenemia.

PMID- 10925666
TI  - [The syndrome of posttraumatic deregulation of the neuroendocrine-immune system
      and the tasks of health-resort therapy].
AB  - Examination of 150 patients with syndrome of immunoendocrinonervous system
      dysregulation (SIENDR) caused in 70% of cases by trauma has shown that this
      syndrome is characterized by hormonal disorders, immunodeficiency followed by
      visceral pathology (gynecological and gastroenterological, in particular).
      Anatomical substrate of the syndrome is impairment of
      hypothalamohypophyseoadrenal complex. Recognition of SIENDR is important for
      physiotherapist as it allows to treat combined diseases with mineral baths,
      drinking mineral water and inhalations.

PMID- 10925667
TI  - [The comparative efficacy of methods for the cryo-electropulse therapy of
      osteoarthrosis patients].
AB  - Comparative trials of two methods of cryoelectroimpulse therapy in combination
      with kinesitherapy and massage performed in 132 patients with osteoarthritis (OA)
      demonstrated that both methods relieve pain syndrome, improve peripheral
      circulation, condition of the neuromuscular system. Overall course effectiveness
      of parallel use of cryotherapy and transcutaneous electroneurostimulation (cryo
      TCENS) combined with exercise and massage was found less than that of cryotherapy
      and sinusoidal modulated currents (cryoamplipulsetherapy). However, the effect of
      a single cryo-TCENS procedure was rather high. This may be explained by a labile
      technique which allows impact on the most painful (trigger) zones in OA patients.
      Thus, cryo-TCENS should be applied in short courses (maximum 6 procedures) or in
      single impacts in severe OA pain while cryoamplipulstherapy is more effective in
      courses consisting of 10-12 procedures.

PMID- 10925668
TI  - [Low-intensity laser radiation in the treatment of patients with rheumatoid
      arthritis].

PMID- 10925669
TI  - [Laser therapy in the treatment of the discogenic neurological manifestations of
      spinal osteochondrosis].
AB  - Traction is one of the methods in pathogenetic therapy of spinal osteochondrosis
      (SO), but not all the traction techniques can be applied in the acute stage: the
      antalgic posture, impaired motor activity create difficulties for conducting
      procedures while the acute process endangers paradoxical reaction to the
      treatment. Adjuvant laser therapy reduces pain syndrome and enhances functional
      capacities of the neuromotor system thus providing favourable conditions for
      spinal traction.

PMID- 10925670
TI  - [The physical rehabilitation of patients with lumbar osteochondrosis living close
      to the Semipalatinsk nuclear proving grounds].

PMID- 10925672
TI  - [In Process Citation]

PMID- 10925671
TI  - [The iron carbonate waters of the Maritime Territory].
AB  - Balneological and experimental examinations were made of physiological properties
      of carbonate iron mineral waters of the Primorskiy Territory. The waters were
      found perspective as a source of ecologically healthy water, to prevent diseases,
      to raise nonspecific resistance of the body.

PMID- 10925673
TI  - [The work organization of a department (office) of physiotherapy in a psychiatric
      hospital].

PMID- 10925674
TI  - [Methods of physical rehabilitation in fibromyalgia].

PMID- 10925676
TI  - [The effect of moderate physical loading on the course of allergic reactions in
      an experiment].

PMID- 10925675
TI  - [The effect of sanatorium-health resort treatment using air baths on the
      bronchial patency indices in chronic nonspecific respiratory organ diseases in
      children].

PMID- 10925677
TI  - [Cancer diagnosis using microarray technologies].
AB  - Recently, functional genomics has developed through the use of using microarray
      technologies. These microarray technologies enable us to analyze the expression
      level of numerous genes in various aspects. These systems are suitable for
      understanding the complex nature of the biology of all living things, including
      human beings. They are especially useful for cancer diagnosis, drug screening and
      prediction of toxicity in clinical oncology.

PMID- 10925678
TI  - [Recent advances in surgical treatment for primary lung cancer].
AB  - In the last 10 years, the treatment of primary lung cancer have remarkably
      changed and advanced. Concerning surgical treatment we have seen the introduction
      of thoracoscopic surgery; intentional limited resection of peripheral small lung
      cancer; increased number of reoperation cases for recurrence and second primary
      tumors in resected lung cancer; as well as developments and improvements in new
      anticancer drugs and their adoption to adjuvant therapy and surgical treatments.
      Now, we'll report four points of recent changes and advances in surgical
      treatment for lung cancer.

PMID- 10925679
TI  - [Sentinel lymph node biopsy and axillary lymph node dissection].
AB  - Sentinel lymph node (SLN) biopsy is a useful way of assessing axillary status and
      obviating axillary dissection in patients with node-negative breast cancer. A
      combination of dye- and gamma probe-guided methods can identify SLN more
      accurately and easily than either of these techniques alone. On the other hand,
      SLN biopsy is highly accurate and sensitive in patients with small tumors, and no
      false-negative SLN biopsy has been reported for a breast cancer < 1.0-1.5 cm.
      Moreover, extensive intraoperative examination of SLNs using frozen sections can
      attain a sensitivity comparable to that obtained by histologic examination on the
      permanent sections. In practice, therefore, axillary dissection can be avoided in
      patients with small tumors in whom the SLNs are negative.

PMID- 10925680
TI  - [Current trends in surgical treatment of esophageal cancer].
AB  - Esophagectomy with cervical, mediastinal and abdominal lymph-node dissection has
      contributed to the improved survival of patients with esophageal cancer. However,
      surgery alone cannot provide more satisfactory survival, and new strategies are
      needed to progress survival. For patients in the advanced stage, combined
      therapy, such as chemoradiation followed by surgery, is attempted to improve
      their survival. Three-field lymph node dissection causes a huge surgical stress
      and it is not necessary for all patients. The optimal fields for lymph-node
      dissection should be selected according to the depth of the tumor invasion and
      the location of the primary lesion. Thoracoscopic and/or laparoscopic methods
      have been adopted over recent years adopted to reduce surgical stress.

PMID- 10925681
TI  - [The latest surgical treatment for gastric carcinoma, aiming both at cure and
      postoperative quality of life].
AB  - Based on the progress in both medical techniques and tools, in addition to the
      evaluation of accumulated cases, some new surgical treatments for gastric
      carcinoma have been attempted which aim both at cure and postoperative quality of
      life. Sentinel node navigation surgery, autonerve-preserving gastrectomy,
      laparoscopic surgery and extended surgery combined with neo-adjuvant chemotherapy
      are reviewed as the treatments promising further development. While it is true
      that many problems remain to be settled in each treatment, the advantages of
      these new treatments are greater than those of the standard one. A prudent
      attitude toward the indications and detailed study of the outcome, therefore,
      will be required for these treatments to become standard in the future.

PMID- 10925682
TI  - [Recent advances in colorectal cancer surgery].
AB  - Recent advances in colorectal cancer surgery have been made in improving the cure
      rate after surgery, the preservation of postoperative function, and the
      development of minimally invasive procedures. Indication for wide lymph node
      dissection in rectal cancer surgery is now limited to a smaller number of cases.
      Functional outcome is being improved thanks to the introduction of autonomic
      nerve preserving operations as well as the increasing number of sphincter
      preserving operations. Laparoscopic colectomy for cancer has been practiced for 7
      8 years, and the advantages and disadvantages of this procedure are being
      clarified. Transanal endoscopic microsurgery (TEM) is a minimally invasive
      surgery for rectal tumors in early stages. The procedure is now overtaking the
      posterior surgical approach, which is used less and less in recent years. Future
      goals in colorectal cancer surgery are further improvements in the cure rate and
      the functional results. Minimally invasive surgery may become the established
      procedure after a careful assessment of its cure rate compared to the open
      surgical procedure.

PMID- 10925683
TI  - [Treatment of liver cancer: current status and future prospectives].
AB  - The most common liver cancers are hepatocellular carcinoma (HCC),
      cholangiocellular carcinoma (CCC), and metastatic colorectal cancer. In HCC
      patients, the extent of the surgical resection is limited due to the functional
      status of the underlying cirrhotic liver. Limited resection, transarterial
      catheter embolization, ethanol injection, and microwave coagulation have been
      applied to treat the patients with liver hypofunction; however, the intrahepatic
      recurrence rate was relatively high in those patients. Therefore, liver
      transplantation is the only radical treatment to remove HCC and cirrhotic livers
      with viral infections. Recent advances in anti-viral agents promise to improve
      the outcome after liver transplantation in patients with HCC. On the other hand,
      CCC is outside the indications for liver transplantation because of the broad
      extension of lymph node and nerve plexus. In liver metastasis from colorectal
      cancer, overall survival is not greatly improved, although arterial chemotherapy
      reduces mortality related to liver metastasis. Surgical resection including
      repeated hepatectomy indicates better survival in patients with liver metastases.
      In the future, both CCC and metastatic liver cancer could be candidates for gene
      therapy. For the 21 century, a new therapeutic strategy incorporating clinical
      evidence, molecular biology, and organ replacement needs to be established for
      the treatment of liver cancer.

PMID- 10925684
TI  - [Randomized comparative study of CMF (cyclophosphamide, methotrexate and 5
      fluorouracil) and UFT-tamoxifen regimens as adjuvant chemotherapy after surgery
      for breast cancer: Tochigi Prefectural Study Group for Post-Breast Cancer
      Adjuvant Chemotherapy].
AB  - This prospective randomized study aimed at establishing the optimal postoperative
      adjuvant chemotherapy regimen for premenopausal n+ breast cancer patients. The
      treatments were Regimen A, comprising 6 courses of CMF (cyclophosphamide, 100
      mg/body on days 1-14; methotrexate, 40 mg/m2 on days 1 and 8; and 5-fluorouracil,
      500 mg/m2 on days 1 and 8), and Regimen B, consisting of UFT (300 mg/day) and
      tamoxifen (30 mg/day) administered orally each day for 2 years. Telephone
      registration allocated the patients to the treatment groups by the minimization
      method in relation to the T category, number of n+ lesions and estrogen receptor
      status. Forty-five patients were registered, and 44 of them were eligible (22
      cases each to Regimen A and Regimen B). The principal background factors showed
      no biases between the groups. The adverse reaction incidence was significantly
      higher with Regimen A (90.9% vs 22.7%). The 5-year survival rate was 89.8% with
      Regimen A and 100% with Regimen B, while the 5-year disease-free rates were 64.5%
      and 76.3%, showing no statistical significance. Regimen B showed a better QOL
      rating after 6 months of therapy in relation to nausea-vomiting and hair loss,
      and after 24 months in relation to appetite, sleep, performance status,
      happiness, anorexia and hair loss.

PMID- 10925685
TI  - [Significance of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase
      (DPD) activity in breast cancer tissue].
AB  - TS, DPD, uridine phosphorylase and thymidine phosphorylase are enzymes involved
      in the metabolism of the anticancer drug pyrimidine fluoride. In this study,
      levels of these enzymes were measured in 47 women with primary breast cancer.
      These enzyme levels were then compared to levels determined from breast cancer
      patients who received either preoperative chemotherapy or nothing, in order to
      determine whether they might predict clinical outcome. The TS inhibition rate was
      significantly higher (p < 0.05) in patients receiving preoperative chemotherapy
      (20.4 +/- 13.3%) than in the untreated group (11.4 +/- 9.8%). No other
      significant differences in activity were noted between the treated and untreated
      groups for any of the other enzymes studied. The activity of each enzyme at the
      tumor site and the tumor/normal (T/N) ratio were also compared between patients
      with and without recurrence. The TS inhibition rate at the tumor site was lower
      in recurring cases than in non-recurring cases, and the T/N ratio tended to be
      higher for DPD in patients with recurrences. These findings indicate that the TS
      inhibition rate and DPD activity may be useful predictors for early recurrence of
      breast cancer following surgery.

PMID- 10925686
TI  - [Comparative clinical study on 5-FU concentrations for oral HCFU and i.v. 5-FU].
AB  - Using the cross-over method, the same patients were administered continuous
      intravenous injections of 5-FU and HCFU, an oral derivative of 5-FU widely used
      for breast and colon cancer in Japan. The pharmacokinetics of 5-FU in blood of
      both drugs were then compared. The AUC of the 5-FU concentration in blood of the
      HCFU 100 mg group tended to be higher than that in the 5-FU 250 mg group and
      lower than that in the 5-FU 500 mg group. There was, however, no statistically
      significant difference between the HCFU and 5-FU 250 mg groups (p = 0.3274), or
      between the HCFU and 5-FU 500 mg groups (p = 0.1921).

PMID- 10925687
TI  - [Correlation between pyrimidine nucleoside phosphorylase (PyNPase) and
      clinicopathological factors in patients with gastric cancer].
AB  - Pyrimidine nucleoside phosphorylase (PyNPase) is a general term for enzymes which
      phosphorolyse pyrimidine class nucleosides; convert 5'-deoxy-5-fluorouridine (5'
      DFUR), a fluoropyrimidine class anticancer drug, to an active type of 5
      fluorouracil (5-FU); and demonstrate higher concentrations in tumor tissue. These
      findings have attracted attention from the standpoint of drug delivery systems.
      With regard to immunohistochemical staining studies, PyNPase expression
      correlated with cancer proliferation and metastasis. However, few have shown a
      relation between PyNPase assay and prognosis. We measured PyNPase value in tumor
      tissue of operative specimens from 60 gastric cancer patients. The results showed
      that the PyNPase value in tumor tissue was significantly higher (1.9 times) than
      in normal mucosa. There was no correlation between the PyNPase level in tumor
      tissue and clinicopathologic factors. However, many patients with relatively
      early gastric cancer had high enzyme levels, indicating that PyNPase may
      influence cancer proliferation and metastasis as well as prognosis. By detecting
      such a factor as PyNPase, and clinically applying the results, 5'-DFUR is
      promising for the treatment of patients with respect to prognosis.

PMID- 10925689
TI  - [Preoperative bronchial arterial infusion of docetaxel for squamous cell
      carcinoma of the lung--clinical evaluation and correlation between anti-tumor
      effect and apoptosis].
AB  - As an induction therapy for advanced lung cancer, a patient received bronchial
      arterial infusion of 30 mg/m2 of docetaxel (TXT). Two weeks after infusion,
      although the tumor size was not reduced, the central necrotic area was
      significantly increased. There were no adverse effects. Nineteen days after
      infusion, we performed a right lower lobectomy and lymph nodal dissection. The
      resected specimen was examined by immunohistochemistry and biochemistry. The anti
      tumor effects were evaluated clinically and the correlation between arterial TXT
      infusion therapy and apoptosis was studied. Hematoxylin and eosin staining
      demonstrated moderately differentiated squamous cell carcinoma associated with
      central necrosis, and cells with chromatin condensation scattered in both the
      necrotic areas and the margin of this area. It is thought that these findings
      were the result of this therapy, rather than just the self-necrosis seen in an
      untreated group.

PMID- 10925688
TI  - [Clinical evaluation of granisetron hydrochloride for nausea and vomiting induced
      by oral anticancer drugs].
AB  - We investigated the antiemetic effect, safety and usefulness of granisetron
      hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs
      used in chemotherapy for gastric cancer and colorectal cancer. In the present
      trial, oral administration of granisetron hydrochloride was performed during 5
      days after nausea or vomiting. 1) Clinically, the effective rate of granisetron
      hydrochloride (the percentage of cases in which the drug was assessed as
      "Remarkably effective" or "Effective") was more than 75% on each day of
      administration. There were no adverse events or abnormal laboratory tests. 2) In
      terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or
      "Useful" in 17 out of 23 cases (78.2%). The above results have shown that
      granisetron hydrochloride tablets, administrated orally once daily at a dose of 2
      mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

PMID- 10925690
TI  - [An successful case of combined daily oral administration of UFT and low-dose
      etoposide for multiple metastases of lung cancer].
AB  - The authors treated a 49-year old female patient, who had multiple metastases of
      lung cancer, by combined daily oral administration of UFT and low-dose ETP. She
      was admitted to our hospital due to complaints of cough and dyspnea, and multiple
      nodular shadows were seen in both lungs on chest X-rays. The pulmonary lesion was
      diagnosed as pulmonary metastasis of lung cancer (squamous cell car) by lung
      biopsy under CT-guide. She also had bone metastasis of the ribs and cerebellar
      metastasis from the lung cancer. Combination chemotherapy of UFT 300 mg/body
      daily and etoposide 25 mg/body daily was performed for 13 months. The pulmonary
      metastatic tumors were reduced significantly. No side effects of the
      carcinostatic agents were noted. She is now doing well. Combined daily oral
      administration of UFT and low-dose etoposide is considered to be safe and
      effective, and the treatment useful for recovering QOL in advanced lung cancer
      patients.

PMID- 10925691
TI  - [A patient with multiple pulmonary metastases from colonic cancer who survived
      for 5 years by effectual administration of 5'-DFUR].
AB  - The patient was a 69-year-old woman who had been diagnosed with a bowel
      obstruction due to colonic cancer, with simultaneous multiple pulmonary
      metastases. The primary lesion was resected and 5'-DFUR was administered for 2
      years at an out-patient clinic. During those 2 years, there was no change in CEA
      value and the pulmonary lesions were fading on the roentogenograms. It then
      became doubtful whether the pulmonary shadows were real metastases or not, and 5'
      DFUR administration was discontinued. After stopping the medication, her CEA
      value rose and the tumor shadows increased in intensity. 5'-DFUR was therefore re
      administrated and her CEA value declined. Afterwards, a re-elevation in CEA value
      was seen, and low-dose FP therapy was added on an out-patient basis. Anti-cancer
      chemotherapy of 5'-DFUR (oral) and low-dose FP (i.v.) was contributed to her 5
      year survival.

PMID- 10925692
TI  - [A case of advanced breast cancer associated with humoral hypercalcemia that
      responded to medroxyprogesterone acetate and docetaxel].
AB  - A 67-year-old woman with a left advanced breast cancer was admitted to our
      hospital. Chest CT revealed a parasternal lymph nodal metastasis invading into
      the sternum, an axillary lymph nodal metastasis, and a lung metastasis. The
      clinical stage of the patient was i.v. (T4bN2M1). Laboratory examination showed
      humoral hypercalcemia. After controlling the hypercalcemia with alendronate,
      sodium hydrate she received chemoendocrine therapy with medroxyprogesterone
      acetate (MPA) (800 mg/day) and docetaxel (60 mg/body once every three weeks). A
      complete response was obtained in the primary and metastatic lesions after 3
      cycles of docetaxel. This case suggests the efficacy of the combined therapy with
      MPA and docetaxel on advanced breast cancers.

PMID- 10925693
TI  - [A case of head metastases of breast cancer successfully treated with radiation
      therapy and docetaxel].
AB  - A 68-year-old female underwent radical mastectomy for left breast cancer in
      April, 1995. She was treated with conventional combination chemotherapy (CEF)
      before and after surgery as an adjuvant therapy. She was treated with oral
      tamoxifen (TAM) and/or medroxyprogesterone (MPA) and doxifluridine daily after
      surgery. In May, 1998, she was found to have developed a subcutaneous tumor of
      the head and skull-bone, and a meningeal metastasis. We treated her with 80 mg
      docetaxel (TXT) one time with radiation (total dose 50 Gy), and with 70 mg two
      times. After the combination therapy, she achieved partial remissions of the
      metastases and a decrease in serum CEA. Adverse reactions to TXT were grade 3
      alopecia, grade 3 to 4 neutropenia, grade 2 to 3 stomatitis, and grade 2
      diarrhea. All were tolerable and reversible. The combination therapy of radiation
      and TXT may be a good strategy for recurrent breast cancer.

PMID- 10925694
TI  - [Chemotherapy with mitoxantrone for the treatment of recurrent breast cancer].
AB  - Two cases of recurrent breast cancer are reported in which chemotherapy with
      mitoxantrone proved remarkably effective. Case 1 was a 61-year-old postmenopausal
      female. At 32 postoperative months, multiple metastases of lung and bone were
      found. Following unsuccessful treatment with anthracyclin and an antiestrogenic
      agent, we used MVP modified therapy (mitoxantrone (MIT) 16 mg and vincristine
      (VCR) 1.6 mg once per 4 weeks and medroxyprogesterone acetate (MPA) 1,200 mg/day)
      and 5'-deoxy-5-fluorouridine (5'-DFUR) 800 mg/daily. After 12 cycles were
      performed, the patient showed a partial response (PR) (nearly complete response
      (CR)) on a chest X-ray and bone scintigram. Case 2 was a 49-year-old
      premenopausal female. At 42 postoperative months, a local recurrence was found
      and resection was performed. However, after endocrine therapy with goserelin
      acetate (ZOL) and chemotherapy with CAF (cyclophosphamide, adriamycin and 5-FU)
      and UFT, local recurrence and pleural effusion were found 6 months after surgical
      operation. We then used MVP modified chemotherapy and endocrine therapy with ZOL.
      The patient showed a PR at 9 cycles after therapy. MVP modified chemotherapy is
      considered an effective treatment for recurrent breast cancer, especially for
      adriamycin or epirubicin resistant breast cancer.

PMID- 10925695
TI  - [Pamidronate therapy for lung cancer patients with bone metastasis].

PMID- 10925696
TI  - [Prevention of arthralgia and myalgia from paclitaxel and carboplatin combination
      chemotherapy with Shakuyaku-kanzo-to].

PMID- 10925697
TI  - [Antitumor activity of 1-hexylcarbamoyluracil which is carmofur substituted
      fluorine for hydrogen].

PMID- 10925698
TI  - [Pharmacokinetically guided dose-escalation (PGDE) strategy].
AB  - When a phase I clinical trial is conducted, the dose escalation strategy is most
      critical. According to the results of preclinical trials, a rapid and safe dose
      escalation is necessary. In this regard, a pharmacokinetically guided dose
      escalation (PGDE) strategy has been developed. An accelerated dose escalation is
      conducted by PGDE until reaching 40% target AUC. To determine the MTD of target
      anti-cancer agents, PGDE appears to be useful.

PMID- 10925699
TI  - Phosphatase inhibitors and premature chromosome condensation in human peripheral
      lymphocytes at different cell-cycle phases.
AB  - The cytogenetical reaction of human peripheral lymphocytes to okadaic acid and
      calyculin A was examined. Calyculin A could induce PCC about 20 times more
      effectively than okadaic acid. Their mechanisms of PCC induction were judged
      similar by their dose-dependent manner and chromosome morphology. Contrary to
      earlier studies suggesting that chemicals could not induce PCC in G1 cells where
      little cyclin B is present, the present study showed that calyculin A could
      induce PCC in lymphocytes not only at S and G2/M but also at the second G1 phase
      after PHA stimulation in vitro. PCC was induced slightly in lymphocytes both at
      G0 and the first in vitro G1 phase even when the calyculin A concentration
      increased one hundred fold. It was found that calcium ionophore A23187 increased
      frequencies of G0-PCC induced by calyculin A, although a further refinement is
      necessary to obtain a suitable morphology of G0-PCC for cytogenetic studies.

PMID- 10925701
TI  - Influence of DNA delivery method on gene targeting frequencies in human cells.
AB  - Gene targeting can be used for genetic studies of human cell lines and has
      significant potential for somatic cell gene therapy. These applications are
      however restricted by the low frequency of homologous recombination in higher
      eukaryotes compared to the relatively efficient nonhomologous integration of
      transfected DNA into the genome. As part of our attempts to overcome this
      problem, we compared two widely used transfection methods for their efficiency in
      gene targeting. To our surprise we found that, for conditions that render similar
      frequencies of nonhomologous integrants, lipofection is much less efficient than
      electroporation in generating targeted clones. This suggests that nonhomologous
      and homologous recombination have different requirements for DNA delivery in
      human cells.

PMID- 10925700
TI  - A combination of genetic suppressor elements produces resistance to drugs
      inhibiting DNA replication.
AB  - Many anticancer drugs inhibit DNA replication. To investigate the mechanism of
      permanent growth inhibition after transient arrest of DNA replication, we
      selected genetic suppressor elements (GSEs) conferring resistance to replication
      inhibitor Aphidicolin. Starting from a retroviral expression library carrying
      normalized fragments of human cell cDNA, we isolated four GSEs which, when
      introduced as a combination, produced resistance to Aphidicolin, doxorubicin and
      hydroxyurea in HT1080 fibrosarcoma cells. The four GSEs were derived from ORFX
      bromodomain protein gene, WIZ zinc finger protein gene, the gene for subunit 3 of
      cytochrome c oxidase, and the gene corresponding to an EST with no known
      function. A cell line carrying all four GSEs showed a weaker induction of the
      senescence-like phenotype after treatment with Aphidicolin or doxorubicin; the
      resistance of this cell line was not associated with decreased doxorubicin
      accumulation. These results indicate that combined effects of GSEs derived from
      these four genes increase cellular resistance to replication-inhibiting drugs,
      possibly by inhibiting drug-induced senescence.

PMID- 10925702
TI  - The human RNA helicase A (DDX9) gene maps to the prostate cancer susceptibility
      locus at chromosome band 1q25 and its pseudogene (DDX9P) to 13q22, respectively.
AB  - RNA helicase A is the homolog of the Drosophila maleless protein, an essential
      factor involved in dosage compensation, and plays a crucial role in early
      development in mammals. Here, we have mapped the human RNA helicase A (DDX9) gene
      to the major susceptibility locus for prostate cancer at chromosome band 1q25,
      and its pseudogene (DDX9P) to the band 13q22 by fluorescence in situ
      hybridization, somatic cell hybrid analysis, and assignment of YAC clones,
      respectively.

PMID- 10925703
TI  - Determination of the genotype of a panel of human tumor cell lines for the human
      homologues of yeast cell cycle checkpoint control genes: identification of cell
      lines carrying homoallelic missense base substitutions.
AB  - A number of human homologues of yeast cell cycle checkpoint control genes have
      been identified recently. In this study, the sequence alterations in six of such
      novel human genes (hRAD1, hRAD9, hRAD17, hHUS1, CHK1 and CHES1) were analyzed by
      PCR-single-strand conformational polymorphism (PCR-SSCP) method on a panel of 25
      human tumor cell lines in an attempt to search for possible in vivo cases where
      any of the checkpoint-related genes are altered in human systems. For hRAD9,
      hHUS1 or CHK1, no SSCP variant was detected in any of the cell lines tested,
      indicating a high stability of these genes in human cancer. Most of the SSCP
      variants found in the other three genes were due to single nucleotide base
      substitutions. Two cell lines were found to be homozygous for missense-type base
      substitutions, i.e., Saos-2 was homoallelic for 1637T-->G in hRAD17; and
      COLO320DM for 1189G-->A in CHES1, indicating a possible use of these cell lines
      for further study. The former nucleotide change in hRAD17, which causes a change
      of amino acid from arginine to lysine at codon 546, was supposed to be
      polymorphic. Considering that lysine, but not arginine, is the amino acid that is
      well conserved among fission yeast, mouse and monkey at the corresponding
      position, coexistence of both alleles in human may have a functional or
      selectional implication.

PMID- 10925704
TI  - Introduction of plasmid DNA and oligonucleotides into lung epithelial cells by
      the hemagglutinating virus of Japan (HVJ)-liposome method.
AB  - The hemagglutinating virus of Japan (HVJ) fused with liposomes provides a unique
      transfection vehicle with characteristics of both virus vector and liposome. Here
      we investigate the efficiency and safety of the HVJ-liposome technique in
      delivering foreign genes and oligonucleotides into the lung of the Wistar rat. A
      plasmid vector containing the Escherichia coli beta-galactosidase (beta-gal) gene
      and the chicken beta-actin promoter was transfected via the trachea using the HVJ
      liposome method. Cytochemical staining showed expression of exogenous beta-gal
      activity in airway epithelial cells, alveolar macrophages, and alveolar type II
      cells. This activity persisted at least 28 days after administration of the
      genes. FITC-labeled oligonucleotides also were introduced into the same types of
      lung cells as those expressing beta-gal. After instillation of HVJ-liposome, anti
      HVJ antibodies were detected in the sera of the rats, but even after repeated
      administration of HVJ-liposome, no marked histopathologic change was observed
      while exogenous beta-gal expression was detected in pulmonary cells.

PMID- 10925705
TI  - Impairments of attention following childhood traumatic brain injury.
AB  - Attentional deficits are commonly reported following traumatic brain injury (TBI)
      in adults, although the occurrence of such problems is less well documented in
      young children. This study aimed to investigate residual attentional abilities
      associated with TBI during childhood, by examining a number of aspects of
      attention including sustained, focussed, and divided attention, attentional
      shift, and response inhibition. Eighteen children with a history of TBI, aged
      between 8 and 14 years and 18 non-injured matched controls participated in the
      study. Results show that attentional skills may be differentially impaired after
      TBI, with children who have sustained moderate-to-severe TBI exhibiting
      significant deficits on the following attentional domains: sustain, focus, and
      response inhibition. These findings support the view that attentional impairments
      following pediatric TBI, while not global, may be more generalized than those
      reported for adult samples, perhaps reflecting the relative immaturity of
      attentional skills at the time of injury.

PMID- 10925706
TI  - Latent structure of the Wisconsin Card Sorting Test after pediatric traumatic
      head injury.
AB  - The performance of 80 pediatric patients with traumatic head injury (THI) on the
      Wisconsin Card Sorting Test (WCST; Heaton, Chelune, Talley, Kay, & Curtiss, 1993)
      was examined to determine the underlying latent structure. Exploratory factor
      analysis with oblique rotation identified three factors: response accuracy,
      failure to self-monitor, and learning. The response accuracy factor was directly
      affected by both age and length of coma. Level of performance on this factor also
      covaried with post-injury psychometric intelligence. It is concluded that
      interpretation of the WCST results of children with THI should consider the
      multifactorial nature of the instrument in combination with injury severity
      characteristics and demographic variables.

PMID- 10925707
TI  - Neuropsychological, learning and psychosocial profile of primary school aged
      children with the velo-cardio-facial syndrome (22q11 deletion): evidence for a
      nonverbal learning disability?
AB  - In this exploratory study, the neuropsychological and learning profile of nine
      primary school age children with velo-cardio-facial syndrome (VCFS) was studied
      by systematic neuropsychological testing. In five out of nine children, the
      following profile was found: a VIQ-PIQ discrepancy (in favor of the VIQ),
      significantly better scores (.05 level) for reading (decoding) and spelling
      compared to arithmetic, deficient tactile-perceptual skills (difficulties mainly
      on the left side of the body), weak but not deficient visual-perceptual
      abilities, deficient visual-spatial skills, extremely poor psychomotor skills
      (gross motor skills more deficient than fine motor skills), problems with
      processing of new and complex material, poor visual attention, good auditory
      memory and relatively good language skills. These findings correspond to the
      pattern of neuropsychological assets and deficits that has been described for the
      syndrome of nonverbal learning disabilities (NLD) (Rourke, 1987, 1988, 1989,
      1995). The psychosocial profile of all nine children with VCFS also correspond to
      that of children with NLD. Further studies on the relationship between cognitive
      function, behavior, psychiatric disorder and abnormalities in brain anatomy in
      young people with VCFS will be needed. In clinical practice, it is worthwhile
      exploring in greater depth the neuropsychological functions of children with VCFS
      to rule out NLD, since they may benefit from specific remediation following the
      learning principles of the NLD-treatment.

PMID- 10925708
TI  - Quantitative analyses of schooling effects on executive function in young
      children.
AB  - Developmental studies have demonstrated the utility of select executive function
      (EF) tasks for the early diagnosis of specific learning-related problems (e.g.,
      Snow, 1998). However, previous data demonstrating schooling effects on EF
      measures suggests potential pitfalls in clinical interpretation. In the present
      study three common EF measures, (Wisconsin Card Sort, Thurstone Word Fluency, and
      a mazes task) in addition to a VIQ estimating task, were administered to a cross
      section of 115 children aged 7 to 9. Using a school-entrance cut-off design the
      unique contributions of formal schooling versus age-related changes to
      performance on the EF measures were examined. Schooling effects were both task
      and age-dependent supporting the conclusion that the proper use of EF measures
      with children in this age range depends upon consideration of factors beyond that
      usually depicted in net-effect models.

PMID- 10925709
TI  - Attentional skills in the acute phase following pediatric traumatic brain injury.
AB  - Only a limited number of studies have investigated attention following pediatric
      head-injury. The present study examined sustained attention and processing speed
      in a group of children who had sustained a mild (n = 27), moderate (n = 33) or
      severe (n = 16) traumatic brain injury (TBI). No significant differences were
      evident between the TBI groups on reaction time measures. Results did show that
      the severe TBI group exhibited greater deficits in the area of sustained
      attention, in comparison to children with mild and moderate injuries, in the
      acute stage following traumatic brain injury. This difficulty may impact on the
      future development of skills dependent on intact attentional capacity.

PMID- 10925710
TI  - Acquired procedural dyscalculia associated to a left parietal lesion in a child.
AB  - We report the case of an 11-year-old boy who developed an anarithmetia in
      association with a left temporo-parietal tumor. His oral and written language
      were normal as well as his ability to judge magnitudes, process numbers, read
      operation signs and retrieve number facts. He had a specific difficulty in
      performing the procedures of subtraction, especially when it involved borrowing.
      These skills had been mastered before the present illness. This case shows that
      the components of calculation can be dissociated by brain lesions sustained
      during childhood, while arithmetic abilities are being acquired, thus reinforcing
      findings from developmental dyscalculias, that suggest a modular organisation of
      those skills during development.

PMID- 10925711
TI  - Biological response to endovascular treatment of abdominal aortic aneurysms.

PMID- 10925712
TI  - Spinal cord stimulation in critical limb ischemia. A review.
AB  - This paper reviews the actual clinical experience and alleged working mechanisms
      of spinal cord stimulation (SCS) in the treatment of non-reconstructable critical
      leg ischaemia. SCS appears to be beneficial particularly for relief of pain and
      healing of ischaemic ulcers. The evidence available as to limb salvage is still
      dubious, because most of the studies performed so far are non-randomised, and
      different causes for peripheral ischaemia are studied simultaneously.
      Investigation of the local skin microcirculation, in particular by means of
      transcutaneous oxygen pressure measurements, appears important to select those
      patients that will benefit most of SCS treatment, to predict limb survival and to
      further elucidate the working mechanism of SCS.

PMID- 10925713
TI  - Endoscopic treatment of the carpal tunnel syndrome: review of the recent
      literature.
AB  - The carpal tunnel syndrome is a common pathology, recognized since one and half
      century. Its surgical treatment, median nerve neurolysis, has only been
      popularized 30 years ago. Despite improvement of the surgical technique, two main
      problems remain unsolved: lack of grip strength and "pillar" pain, which can last
      several weeks after surgery. Endoscopy, in a same way as knee meniscectomy or
      cholecystectomy, has contributed to minimize drawbacks of conventional surgery.
      Ten years of experience have improved the material and the technique, the most
      recent series reporting very low complication rates. In experimented hands, and
      with correct indications, endoscopic treatment of carpal tunnel syndrome offers a
      clinical benefit for the patient and an economical one for the Society.

PMID- 10925714
TI  - Phonosurgery in gender dysphoria.
AB  - A particular type of phonosurgery is voice change surgery in cases of gender
      dysphoria. This paper presents a review of the surgical techniques available for
      raising or lowering speaking fundamental frequency. A cricothyroid approximation
      to raise the vocal pitch is the most common procedure. This procedure results in
      an increase of about one octave immediately postoperatively and about half an
      octave after stabilization of the voice.

PMID- 10925715
TI  - The inferior non recurrent laryngeal nerve: a major surgical risk during
      thyroidectomy.
AB  - It is now widely established that systematic intraoperative location and diligent
      dissection of the recurrent inferior laryngeal nerve during thyroidectomy are the
      keystones to assure its anatomic and functional preservation. The possibility of
      abnormal routes, like a non-recurrent cervical course of the inferior laryngeal
      nerve is an additional major argument for its systematic identification to avoid
      surgical damage. In 2517 cervicotomies performed between 1992 and 1997 for at
      least right thyroid lobe excision or parathyroid glands exploration, 20 cases of
      non recurrent laryngeal nerve were identified (0.79%). The embryological nature
      of such a nervous anatomical variation results originally from a vascular
      disorder, named arteria lusoria in which the fourth right aortic arch is
      abnormally absorbed, being therefore unable to drag the right recurrent laryngeal
      nerve down when the heart descends and the neck elongates during embryonic
      development. The surgeon must be aware of the possibility of a non recurrent
      laryngeal nerve, which arises directly from the cervical vagus and therefore
      represents a severe potential pitfall during thyroidectomy. Given the absence of
      reliable clinical symptoms and signs or investigations indicating preoperatively
      the possibility of a non recurrent nerve, guidelines are given to prevent
      intraoperatively this major surgical risk.

PMID- 10925716
TI  - Tailgut cysts: rare retrorectal tumours.
AB  - Two patients presented with tailgut cysts. The first patient complained of pain
      and pressure in the sacrococcygeal region. The second patient had developed a
      cystic mass superficial to the coccyx. Pelvic CT scans of both patients
      demonstrated a retrorectal mass. Both tumours were excised through a posterior
      para-sacrococcygeal approach with resection of the coccyx.

PMID- 10925717
TI  - Isolated colonic injury following blunt abdominal trauma.
AB  - A case of delayed diagnosis of colonic injury after blunt abdominal trauma
      leading to faecal peritonitis is presented. Diagnostic problems and possibilities
      as well as treatment of these injuries are reviewed. The key to diagnosis remains
      the serial clinical and ultrasound examinations.

PMID- 10925718
TI  - Rupture of a thoracic aneurysm in the left bronchus.
AB  - Aortobronchic fistula is a very unusual complication of thoracic aneurysm. We
      report the case of a 71-year old man with rupture of a thoracic aortic aneurysm
      in the left main bronchus. The patient had suffered a car crash fifteen years
      ago, without any evidence of aortic rupture at the time. Thereafter, he developed
      an aortic isthmic dilation (36 mm in diameter). The patient suffered from long
      standing pulmonary insufficiency and emphysema and was admitted several times on
      an urgent basis for acute dyspnea. During an hospitalization for respiratory
      distress, he presented haemoptysis and left lung hyperinflation secondary to
      partial fistulization and extrinsic compression of the main left bronchus.
      Isthmic aortic resection and prosthetic grafting was performed and the left main
      bronchus was closed by an autologous pericardial patch. Ten days later, following
      an air-leak from the bronchial closure, a transposed latissimus dorsi flap was
      used by the plastic surgeon to repair the defect. Nevertheless, the patient died
      from multisystemic failure six weeks later.

PMID- 10925719
TI  - What means: educating a surgical trainee into a fully responsible surgeon?

PMID- 10925720
TI  - What are the current criteria to evaluate a surgical trainee?

PMID- 10925721
TI  - Junior surgical trainee: assistant or pupil?

PMID- 10925722
TI  - [Acute liver failure by diphenylhydantoin].
AB  - Diphenylhydantoin is a anticonvulsivant and antiarrhythmic drug. We reported a
      less frequent case of diphenylhydantoin associated acute hepatotoxicity in a 18
      year old woman who immediately after child birth presented generalized tonic
      clonic seizures secondary to arachnoid cyst in the left temporal-lobe. The
      patient developed a mononucleosis like coinciding with previous descriptions.
      Histological features observed in the liver biopsy specimen showed compatible
      changes with toxic acute liver failure (ALF). In the few cases published of ALF
      for Diphenylhydantoin is not specifically pointed out the absence of hepatic
      encephalopathy as it happened to our patient.

PMID- 10925723
TI  - [Clinic-epidemiological significance of drug hepatotoxicity in liver disease
      consultation].
AB  - To assess epidemiological and clinical significance of drug hepatotoxicity in the
      setting of liver diseases consultation, ten thousand and three hundred forty two
      prospectively designed clinical records from patient cared for in our Liver Unit
      in the period 1988-1998 were incorporated into the study; 58 out of 10,342
      (prevalence = 5.6%) fulfilled at least the first three of the following causality
      requirements: 1.--Liver injury associated in time to drug exposition; 2.-
      Negative evaluation of more common other etiologies; (alcohol, viruses,
      immunologic, metabolic, etc) 3.--Favourable response to drug withdrawal (ALT <
      50% of baseline in 8 to 30 days in acute hepatitis type, and alkaline phosphatase
      and/or total bilirubin < 50% of baseline up to 6 months, in acute cholestasis) 4.
      -Inadverted or rarely prescribed positive challenge. Acute hepatitis type of
      injury were considered when serum ALT rise 8 times or more above normal superior
      level with alkaline phosphatase (APh) below 3 times; "pure" cholestasis when APh
      rise 3 times or more above normal with ALT below 8 times; mixed acute injury or
      cholestatic hepatitis when both ALT and APh were elevated above 8 and 3 times
      respectively, and indeterminate type when both enzymes were below the referred
      levels. Chronic injury were considered when six or more month of evolution and
      compatible liver histology happens. Clinical severity were expressed as mild
      (absence of major clinical complications, serum bilirubin < 5 mg/dl and
      prothrombin concentration > 75%), moderate (presence of clinical complications,
      bilirubin > 5 mg/dl and prothrombin concentration between 50-75%), and severe
      (major clinical complications with bilirubin > 5 mg/dl and prothrombin
      concentration < 50%). Female/male ratio was 1.4:1, with age average 39 years (R =
      15-77) and major concentration of cases above 40. More than 50% of cases received
      2 or more drugs. Jaundice was present in 60.4%, and systemic manifestations of
      hypersensibility (fever, adenomegalies, rush, mononucleosis like syndrome,
      eosinophilia) in 29.3%. Acute injury represented 91.4% of the cases: 41.4% acute
      hepatitis, 15.5% "pure" cholestasis, 24.1% cholestatic hepatitis, and 10.3%
      indeterminate type. Four patients (4.5% of acute injury cases) were presented as
      severe acute liver failure, leading to liver transplant in one of them, drug
      association (INH-rifampicin and carbamazepine-phenobarbital) and inadverted
      challenge (sulphonamides and pemoline) were associated to clinical severity.
      Chronic injury were found in five patient (8.6%), four of them associated to
      chronic hepatitis and the other one to a ductopenic syndrome. Six drugs
      represented 53.4% of our cases; oral contraceptives (7 cases), INH alone or
      combined with rifampicin (6 cases), sulfonamides and clorpropamida (5 cases
      each), carbamazepine and amiodarone (4 cases each). Normalization of liver
      enzymes after drug suppression took 2 to 8 weeks in acute hepatitis type (X = 4
      weeks), 4 to 20 in "pure" cholestasis (X = 12 weeks) and 8 to 24 weeks in
      cholestatic hepatitis or mixed type (X = 16 weeks). Two cases of chronic
      hepatitis normalize the histological activity index in 20 and 18 month
      respectively, one case remains as chronic hepatitis at 10 month and the other one
      progress to cirrhosis; the ductopenic syndrome normalize histology in 19 months
      receiving urso-deoxicolic acid, 10 mg/k/day.

PMID- 10925724
TI  - Quantification of fecal neutrophils by MPO determination (myeloperoxidase) in
      patients with invasive diarrhea. Cuantificacion de neutrofilos fecales mediante
      la determinacion de MPO (Mieloperoxidasa) en pacientes con diarrea invasiva.
AB  - Myeloperoxidase (MPO), a specific polymorphonuclear leukocyte enzyme, has been
      used previously to quantify the number of neutrophils in tissue. MPO activity was
      found to be linearly related to the number of neutrophil cells. In an attempt to
      use this method in leukocytes measuring in stool, fecal MPO was solubilized with
      hexadecyltrimethylammonium bromide and the MPO activity was measured by a
      dianisidine-H2O2 assay. Stools from 10 normal subjects and 39 patients with
      diarrhea produced by enteropathogenic bacteria were examined for leukocytes by
      MPO activity as well as microscopically using methylene blue stain, MPO activity
      was positive in 36 patients (92%) and leukocytes were present by microscopic
      observation in 30 (77%). Fecal leukocytes were not found in healthy controls and
      the MPO activity was undectable. Stool MPO activity had a range of from 1.6 to
      2,830.0 x 10(3) UMPO per gram of feces (median 460.0). The number of neutrophils
      obtained through MPO activity had a range of 6.0 to 13,216.0/ mm3 (median
      1,261.0). Fecal MPO activity is a simple biochemical assay for the detection and
      quantification of fecal leukocytes.

PMID- 10925725
TI  - [Esophageal radiology in the patient with dysphagia: review in 333 patients].
AB  - The authors presents a retrospective analysis from the results of radiologic
      examinations in patients with dysphagia in a private clinic. They were 333
      patients studied with conventional and digital radiology, using conventional
      technic to perform the examines. The special technique (barium/crushing-ice) was
      used to provoke the possible motility disorders. The results were normal in 105
      patients (31.5%) and pathologic in 228 patients (68.5%).

PMID- 10925726
TI  - [Anti-HCV in patients transfused, in a health area attended by a family
      physician. Medical Office 19 de Abril].
AB  - The infection by the virus the hepatitis C (VHC) constitutes a health problem at
      world level. This situation has resulted in numerous researchers developing and
      using different means of diagnosis in order to know the actual prevalence of the
      virus. The main way of VHC transmission is blood and/or haemoderivates
      transfusion. It has been estimated that 90% of post-transfusional hepatitis are
      VHC. This situation motivated us to make a descriptive and transversal study in
      order to screen VHC in a group of patients who had been transfused with blood
      and/or haemoderivates. The patients came from the medical doctor's office N(o) 36
      belonging the polyclinic "19 de April", in the city of Havana. The objective was
      to study the prevalence of the virus in our area and also to precise the main
      causes of the transfusion and the relationship between their number and the
      presence of anti-HVC. We found 35 patients who had been transfused (5.3%) in the
      population (653), and from these, three patients (8.5%) were anti-HVC positive.
      The main cause for having been transfused was anemia, being sicklemia the entity,
      which reported more patients with anti VHC positive. We also conclude that the
      probability of having an anti-HVC positive increases proportionally to the number
      of transfusions; these were significant differences between the groups who
      received a greater and a smaller number of transfusions.

PMID- 10925727
TI  - [Is there pancreatic regeneration? Morphological and functional certification
      after a corporocaudal splenopancreatectomy/].
AB  - INTRODUCTION: The process of pancreatic regeneration, well known and accepted, is
      less known than the hepatic and includes different mechanisms and factors.
      Pancreatic regeneration is better known in acute pancreatitis. After an extensive
      pancreatic necrosis, the morphological and functional regeneration is assessed by
      dynamic computed tomography associated with normalization of glycemia and the
      exocrine function. Different groups identified and evaluated experimentally and
      clinically the actions of multiple factors involved in the process of pancreatic
      regeneration. Even difficult to assess, pancreatic regeneration after partial
      pancreatectomy is well documented and of capital importance. CASE REPORT: A 57
      year-old woman with discomfort in the upper-left abdominal quadrant. CT scans
      showed a tumor in the body and tail of the pancreas adherent to the spleen.
      Preoperative CA 19-9 was normal. She was operated on and the tumor resected en
      bloc with the spleen. Only the head of the pancreas was preserved. Intraoperative
      pathological examination of the specimen showed a mucinous cistoadenoma with no
      malignant degeneration. Postoperative course was uneventful and discharged at
      p.o. day 10, with ongoing diabetes. Four month later she presented pain in the
      upper-left quadrant with hyperamylasemia. CT scans showed a normal body and tail
      with an image of pseudocyst at the top of the pancreatic tail. One year after the
      initial surgery she remained asymptomatic, without diabetes and with no dietary
      restrictions. Further CT controls showed images of the entire regeneration of the
      body and tail of the pancreas. DISCUSSION: Several phenomena are well known and
      accepted to be associated with the regeneration of the pancreas. In 1965,
      Tiscornia et al demonstrated the restoration of the pancreatic exocrine function
      after 6 weeks of selective occlusion of the pancreatic duct. The authors proposed
      pancreatic regeneration as responsible of morphological, histological and
      functional changes observed in operated patients where the pancreatic duct was
      decompressed by an anastomosis to the small bowel and constitutes the rational
      basis for surgical treatment of chronic pancreatitis. Several humoral factors
      seems to be involved in pancreatic regeneration acting by a specific receptors
      mechanisms, like Bombesin, Octeotride, FGF (Fibroblast Growth Factor) and TGF
      (Transforming Growth Factor). Friess et al demonstrated increased levels of TGF
      in acute pancreatitis and considered it to be responsible of the pancreatic
      regeneration. Waguri et al experimentally demonstrated a double mechanism
      involved in the regeneration of B-cells: cellular and humoral ways could vary
      according to different situations. Less evident are the mechanisms involved after
      surgical pancreatic resection. Kato et al demonstrated the importance of zinc
      after partial pancreatic resection in dogs. Up to now, there are no other
      associations experimentally nor in humans. Our case showed in several CT scans
      control the presence of a normal pancreatic body and tails after a
      splenopancreatectomy, with restoration of endocrine and exocrine functions.
      Probably, several mechanisms were involved in this case. Further investigations
      will elucidate the answered. CONCLUSIONS: Pancreatic regeneration was confirmed
      by CT scans images and also functionally after an extensive resection. Future
      similar findings could be of great clinical importance.

PMID- 10925728
TI  - [Simultaneous digestive tumors].
AB  - Synchronous and metachronous gastrointestinal tumors are well know entities,
      describing malignant tumors placed in the same organ, at the time of initial
      diagnosis or during the follow-up control. I would like to present two cases of
      malignant tumors placed in different organs of the digestive tube, at the time of
      diagnosis, coining the name simultaneous for these entities, stating laboratory
      finding and signo-symptomatologic interpretation difficulties, and proposing
      endoscopic approach as a valid diagnostic method.

PMID- 10925729
TI  - [Hepatic rupture in pregnancy: report of a case and review of the literature].
AB  - A hepatic rupture case in a pregnancy is reported. A bibliographic revision
      during the last fifteen years has been carried out in which: epidemiology, risk
      factors, etiopatogenia, clinic, complementary exams, presage and treatment.

PMID- 10925730
TI  - [Barrett s epithelium: clinical review].
AB  - In this paper we review the literature about regarding etiology, natural history,
      methods of study and treatment of Barrett's esophagus. Likewise we review our
      personal experience as well as the one at national level.

PMID- 10925731
TI  - [Hepatotoxicity produced by drugs].

PMID- 10925732
TI  - [Epidemiology of hepatitis C].

PMID- 10925733
TI  - Factors affecting levodopa effects in Parkinson's disease.
AB  - Levodopa is the gold standard for the treatment of Parkinson's disease (PD)
      because of its outstanding clinical efficacy. However, the majority of patients
      experience various adverse reactions, including the wearing-off phenomenon, the
      on-off phenomenon, dyskinesia and psychiatric symptoms. The response to levodopa
      depends not only on the intrinsic responsiveness of the patients, but also on
      various other important factors including the type of levodopa preparation, its
      absorption/metabolism, the blood-brain barrier, age at onset of disease and
      concomitant use of anti-parkinsonian drugs. This review summarizes factors which
      influence the effects of levodopa in PD. To minimize levodopa-induced adverse
      reactions and to relieve long-term parkinsonian symptoms, levodopa therapy should
      be conducted by taking these factors into consideration.

PMID- 10925734
TI  - Heat shock protein 72 expression in the right ventricle of patients undergoing
      congenital cardiac surgery.
AB  - While heat shock protein (HSP) 72 is known as a stress protein, there have been
      no reports of HSP 72 expression in patients who have undergone surgery for
      congenital heart disease. Fourteen patients (7 males and 7 females) who had
      undergone surgery for congenital heart disease were studied. The ages of the
      patients ranged from 2 months to 43 years old (mean 6.5 +/- 10.8 years old;
      median 3.0 years old). The diagnoses were Tetralogy of Fallot in seven, pulmonary
      atresia with ventricular septal defect (VSD) in three, complex anomalies in
      three, and VSD in one patient. Histological study and HSP analysis using Western
      blots and immunostaining with anti-HSP 72 monoclonal antibody were performed for
      right ventricular muscle samples resected during the surgery. The histological
      findings showed hypertrophic changes of ventricular cardiomyocytes in all samples
      studied. Western blots detected HSP 72 expression of various degrees in all
      specimens. Immunostaining using monoclonal antibody against HSP 72 showed that
      the protein was present in the nuclei and cytoplasm of cardiomyocytes. In
      conclusion, although it is difficult to determine the cause of the "stress" that
      triggers HSP 72 expression in cardiomyocytes, low O2 saturation and pressure
      overload might act as a "stress", and the only common factor that induced HSP 72
      in every sample was hypertrophy.

PMID- 10925735
TI  - The perineuronal proteoglycan surface coat in the adult rat brain, with special
      reference to its reactions to Gomori's ammoniacal silver.
AB  - The present study showed that many neurons in the adult rat brain possessed a
      perineuronal sulfated proteoglycan surface coat which reacted to cationic iron
      colloid and aldehyde fuchsin. This surface coat was stained supravitally with
      Ehrlich's methylene blue and doubly stained with Ehrlich's methylene blue and
      aldehyde fuchsin. The surface coat was also stained with Gomori's ammoniacal
      silver and doubly stained with Gomori's ammoniacal silver and cationic iron
      colloid. The surface coat was usually expressed together with a nerve cell
      surface glycoprotein net detectable with lectin Wisteria floribunda agglutinin.
      These findings indicate that the perineuronal proteoglycan surface coat is
      identical to Cajal's superficial reticulum and contains some collagenous
      elements. It was further demonstrated that collagenase digestion erased Gomori's
      ammoniacal silver impregnation within the perineuronal proteoglycan surface coat.

PMID- 10925736
TI  - Prognostic value of vascular endothelial growth factor expression in primary lung
      carcinoma.
AB  - To investigate whether an association exists between vascular endothelial growth
      factor (VEGF) expression and tumor prognosis in primary lung carcinoma, we used
      immunohistochemical techniques to analyze microvessel density and VEGF expression
      in lung carcinoma tissue from 98 patients. Tissue had been fresh-frozen at the
      time of operation and preserved for more than 5 years. The results indicated that
      VEGF expression was positive for 50 of the 98 patients (51.0%), with 27 (27.6%)
      being weakly positive and 23 (23.5%) being strongly positive. The microvessel
      density in tissue showing weakly positive and strongly positive VEGF expression
      was significantly higher than that in VEGF-negative tumor tissue (P < 0.05:
      negative vs. weakly positive, P < 0.01: negative vs. strongly positive), we
      showed demonstrating that VEGF expression was significantly associated with
      intratumoral microvessel density. The 5-year survival rates were 8.7% for
      strongly VEGF-positive patients, 43.9% for weakly VEGF-positive patients and
      79.2% for VEGF-negative patients, respectively (P < 0.01: negative vs. weakly
      positive or strongly positive). Furthermore, multivariate analysis employing
      multiple regression analysis indicated that VEGF expression correlates highly
      with the overall survival rates of patients with primary lung carcinoma. Two
      variables, N status and VEGF expression, were found to be significant prognostic
      factors (P < 0.01). The results of this study suggest that VEGF expression is
      associated with intratumoral microvessel density. VEGF expression may constitute
      important independent prognostic evidence that can help us in predicting the
      outcomes of patients with primary lung carcinomas.

PMID- 10925737
TI  - Effects of medical education on attitudes towards mental illness among medical
      students: a five-year follow-up study.
AB  - In order to clarify the effects of medical education on attitudes towards mental
      illness among medical students, a follow-up study was conducted. All 100 students
      entering Kochi Medical School in 1988 were subjects. The initial questionnaire
      survey was conducted in 1988, and followed up in 1993. Response rate was 69% in
      the initial survey, and 83% in the follow-up study. By the time of the follow-up,
      all of the students had completed their medical education, including courses in
      psychiatry and mental health. Results were as follows: At the follow-up study, 1)
      a significantly higher percentage of students replied that they accepted the
      mentally ill as co-workers; 2) significantly favorable changes were observed in
      attitudes towards psychiatric services; 3) optimism about the effectiveness of
      treatment for mental illness at an early stage and prevention of mental illness
      had decreased; and 4) no change was observed in attitudes toward human rights of
      the mentally ill, except in the case of one item stating that the mentally ill
      should not have children in order to avoid hereditary handicaps, with which a
      lower percentage agreed. Conclusively, medical education can play an important
      role in attitudes towards mental illness.

PMID- 10925738
TI  - Clinical significance and frequency of Blastocystis hominis in Turkish patients
      with hematological malignancy.
AB  - The effect of Blastocystis hominis (B. hominis) in both immunocompetent and
      immunocompromised subjects has been the subject of debate in recent years, mostly
      in response to its unknown pathogenicity and frequency of occurrence. We
      performed a non-randomised, open labelled, single institute study in our hospital
      in order to investigate the clinical significance and frequency of B. hominis in
      patients suffering from hematological malignancy (HM) who displayed symptoms of
      gastrointestinal diseases during the period of chemotherapy-induced neutropenia.
      The presence and potential role of other intestinal inclusive of parasites were
      also studied. At least 3 stool samples from each of 206 HM patients with
      gastrointestinal complaints (the HM group) were studied. These were compared with
      stool samples from a control group of 200 patients without HM who were also
      suffering from gastrointestinal complaints. Samples were studied with saline
      lugol, formalin-ether, and trichome staining methods. Groups were comparable in
      terms of gender, age and type of gastrointestinal complaints. In the HM group,
      the most common parasite was B. hominis. In this group, 23 patients (13%) had B.
      hominis, while in the control group only 2 patients (1%) had B. hominis. This
      difference was statistically significant (P < 0.05). Symptoms were non-specific
      for B. hominis or other parasites in the HM group. The predominant symptoms in
      both groups were abdominal pain (87-89.5%), diarrhea (70-89.5%), and flatulence
      (74-68.4%). Although all patients with HM were symptom-free at the end of
      treatment with oral metranidazol (1,500 mg per day for 10 days) 2 patients with
      HM had positive stool samples containing an insignificant number of parasites (<
      5 cells per field). In conclusion, it appears that B. hominis is not rare and
      should be considered in patients with HM who have gastrointestinal complaints
      while being treated with chemotherapy. Furthermore, metranidazol appears to be
      effective in treating B. hominis infection.

PMID- 10925739
TI  - High prevalence of hepatitis C in patients with thalassemia and patients with
      liver diseases in Myanmar (Burma).
AB  - We conducted Myanmar-Japan cooperation studies on hepatitis B and hepatitis C
      virus markers in patients with thalassemias and those with liver diseases. Among
      the 102 patients with liver diseases, 92% had a history of hepatitis B virus
      infection (antibody to hepatitis B core antigen positive), 35% were hepatitis B
      surface antigen positive, 39% were positive for anti-HCV. Among 28 patients with
      hepatocellular carcinoma, 46% had hepatitis B surface antigen, 21.4% had antibody
      to hepatitis C virus, and 7% were positive for both hepatitis B surface antigen
      and anti hepatitis C virus. The history of HCV infection among blood recipients
      at the Haematology Department of the Yangon General Hospital and at the Yangon
      Children's Hospital was found to be 55.5% and 46.7%, respectively, which is
      comparable to the history of hepatitis B infection (66.7% and 46.7%,
      respectively). This preliminary survey also encountered 2 cases positive for anti
      HCV among 34 voluntary blood donors. This survey is the first one to report that
      hepatitis C is at the epidemic stage in Myanmar. As there is no effective
      treatment for hepatitis C in this country, a screening program for blood used in
      transfusion should be started immediately.

PMID- 10925740
TI  - Uncommon noninflammatory osteoarticular disorders. Introduction.

PMID- 10925741
TI  - Bone disorders: a radiological approach.
AB  - The radiological interpretation of bone and joint disease has emerged as a
      subspecialty in its own right. This chapter offers simple guidelines for the
      approach to a plain film examination that has been taken in a patient with a non
      inflammatory arthritis. It does not discuss what films should be taken or when.
      Instead, it focuses on what to look for and where. Emphasis is placed on unusual
      features that may trigger the thought 'This doesn't look like ordinary
      osteoarthritis.' One does not know, of course, that the patient has an unusual
      cause of arthritis until the radiograph has been taken. Hence the radiographs of
      all patients deserve to be analysed properly, for only then will the unusual not
      become the undiagnosed.

PMID- 10925742
TI  - Non-inflammatory enthesopathies of the spine: a diagnostic approach.
AB  - Ankylosing vertebral hyperostosis, or hyperostotic disease, is an ossification of
      the entheses, the regions of insertion of tendons, ligaments or joint capsules
      into the bone. These ossifications create intervertebral bridges (ossifications
      of the common anterior, lateral and posterior intervertebral ligaments as well as
      of the ligamentum flavum), which are responsible for the potential signs of the
      disease: back and neck pain and stiffness, spinal cord compression at the
      cervical level and lumbar canal stenosis at the lumbar level. The bony epiphyses
      are the sites of bony appositions, or enthesophytes, which may compromise joint
      mobility and increase the risk of secondary osteoarthritis, causing hip and knee
      disorders in particular. These degenerative joint diseases may eventually
      necessitate total replacement. In this case, the risk of re-ossification around
      the prosthesis must be averted by the immediate postoperative prescription of
      anti-inflammatory medication for 1-2 weeks.

PMID- 10925743
TI  - Hereditary disorders mimicking and/or causing premature osteoarthritis.
AB  - Osteoarthritis is the most common joint disease, causing considerable disability
      and impairment of quality of life. Hereditary osteochondrodysplasias and some
      inborn errors of metabolism may mimic or cause premature osteoarthritis.
      Osteochondrodysplasias usually cause joint deformities, such as coxa vara or genu
      varum, which can cause abnormal biomechanics. In most of these disorders, the
      articular cartilage is originally defective as a result of genetically determined
      collagen or matrix protein abnormalities, or the deposition of
      mucopolysaccharides. In the case of inborn errors of metabolism, the pathological
      process affects healthy articular structures, causing secondary osteoarthritis.
      In alkaptonuria, the pathological deposition of polymerized homogenistic acid
      causes defective changes in cartilage, articular capsule and tendons. In Wilson's
      disease, the premature osteoarthritis might be caused by the copper deposition.
      It is worth paying attention to these rare disorders, even when they are mild or
      incomplete, because early diagnosis can lead to prevention and effective
      treatment. In addition, research is discovering the specific gene defects and
      molecular abnormalities that are responsible for disease expression. This may in
      turn lead to opportunities for prenatal diagnosis; thus, genetic counselling and
      gene replacement therapy may be a realistic possibility in the near future.

PMID- 10925744
TI  - Osteoarticular disorders of endocrine origin.
AB  - Endocrine diseases may present with musculoskeletal complaints, and their
      outcome, even after endocrine control, can be impaired by bone and joint
      disorders. All musculoskeletal structures, including bone, cartilage, synovium,
      tendons and ligaments, can be involved by some processes triggered by the
      endocrine disorder and its related disturbances of homeostasis, including that of
      growth factors. Endocrine disorders may account for 20-30% of all cases of
      osteopenia or osteoporosis in adults, the main causes being central and
      peripheral hypogonadism, endogenous and exogenous hypercorticism or
      hyperthyroidism, and primary hyperparathyroidism. The physician should be aware
      of these identifiable and treatable causes of bone loss when interpreting bone
      mineral density measurements. It is also valuable to evaluate bone status in
      patients diagnosed with these endocrine disorders. Specific bone therapeutic
      measures could be discussed. Other frequent musculoskeletal features include
      myopathy and joint and soft tissue involvement. Endocrine myopathy is frequent in
      most of the endocrine disorders and is non-specific since proximal painless
      muscle weakness associated with normal serum enzyme levels and an uncommonly
      encountered electromyogram myopathic pattern are present in these diseases. Soft
      tissue involvement is also a frequent consequence of acromegaly, hypothyroidism
      and diabetes mellitus. There is also a risk of nerve entrapment syndromes in
      these conditions. Specific arthropathies are the hallmark of acromegaly at the
      spinal and peripheral joints. Neuroarthropathies are a severe complication of
      diabetes mellitus as a result of infection, neuropathy and vasculopathy. In all
      these settings, the physician should be aware that endocrine disorders are part
      of the differential diagnosis and, conversely, that these articular and peri
      articular lesions should be managed independently of the control of the
      underlying endocrine condition, a specific outcome being borne in mind.

PMID- 10925745
TI  - Haemochromatosis.
AB  - Arthropathy is a prominent but still underappreciated aspect of haemochromatosis.
      Clinical descriptions have characterized typical features, including involvement
      of the 2nd-3rd metacarpophalangeal joints with an osteoarthritic-like picture.
      Virtually any joint can be involved and can be a presenting clue to the
      underlying disease. The recent demonstration of the HFE gene on chromosome 6 with
      characteristic mutations should encourage further investigation. However, the
      pathogenesis of the arthropathy is not yet well understood. Treatment is also
      empirical and often unsatisfactory. Phlebotomies, although valuable to treat or
      prevent other features, do not predictably benefit the arthropathy.

PMID- 10925746
TI  - Osteoarticular disorders of renal origin: disease-related and iatrogenic.
AB  - Osteoarticular disorders significantly limit the quality of long-term survival
      with chronic renal failure. beta 2M amyloidosis is a complication of chronic
      renal failure that has been recognized mostly in patients receiving long-term
      haemodialysis. Patients with beta 2M amyloidosis typically present with the triad
      of shoulder periarthritis, carpal tunnel syndrome, and flexor tenosynovitis of
      the hands. Other musculoskeletal manifestations of beta 2M amyloidosis include
      destructive spondyloarthropathy, cervico-occipital pseudotumours, bone cysts, and
      pathological fractures. At present, only renal transplantation may slow or halt
      the progession of beta 2M amyloidosis. Crystal-induced arthropathy, most commonly
      caused by basic calcium phosphate crystals, is an important cause of acute joint
      inflammation in the patient with renal failure. The incidence of bone and joint
      infection is increased in patients undergoing dialysis. Haemodialysis and
      peritoneal dialysis are also associated with an erosive or destructive
      arthropathy of finger joints, which is not explained by local amyloid deposition.

PMID- 10925747
TI  - Osteoarticular disorders of haematological origin.
AB  - Clinical abnormalities of the musculoskeletal system may be the first
      manifestation of sickle haemoglobinopathies, leukaemias, lymphomas and
      haemophilia. In addition to this, known patients with these diseases exhibit a
      variety of osteoarticular features. The painful crisis is the most common
      manifestation of sickle cell disorders, but avascular necrosis, osteomyelitis and
      various forms of arthritides are also common. In haematological malignancies,
      bone pain and arthritis may occur at any stage of the disease. The diagnosis must
      be confirmed by the presence of malignant cells on histological examination of
      various samples. Haemarthrosis is the main symptom of haemophilia. It needs early
      treatment to avoid damage to the joints. The availability of new safe coagulation
      factors has improved the prognosis of haemophilia.

PMID- 10925748
TI  - Musculoskeletal problems of neurogenic origin.
AB  - A number of neurological disorders can manifest as isolated pain or as joint,
      muscle or bone alterations. These manifestations can raise significant diagnostic
      challenges when they occur early, before the development of neurological and/or
      radiological abnormalities. This chapter discusses neuropathic
      osteoarthropathies, neurofibromatosis, Parkinson's disease, multiple sclerosis
      and the complications of central nervous system lesions.

PMID- 10925749
TI  - Heritable disorders of connective tissue.
AB  - This chapter seeks to draw readers' attention to the importance of the heritable
      disorders of connective tissue in clinical practice. It describes the principal
      features of the Marfan and Ehlers-Danlos syndromes, osteogenesis imperfecta and
      benign joint hypermobility syndrome, their clinical and prognostic similarities
      and differences, and their distinguishing features. Recently revised
      international classifications drawing on advances in molecular genetics are
      described in detail. Wherever possible, patients' symptoms are explained on the
      basis of the altered biomechanics of genetically aberrant connective tissue
      matrix proteins. Finally, the chapter draws attention to the often unrecognized
      burden of chronic pain borne by patients with these conditions, a feature of
      which many rheumatologists seem unaware, and sets out a rational and holistic
      approach to treatment and management that is based on the best currently
      available evidence.

PMID- 10925751
TI  - Fibrous dysplasia of bone.
AB  - Fibrous dysplasia of bone is a disease that can involve one or several bones and
      is characterized by bone deformities, pain and iterative fractures. Some patients
      can present with endocrine dysfunction (generally precocious puberty) and
      cutaneous cafe-au-lait spots. Some complications, such as nerve compression and
      malignant transformation, are uncommon. Many patients can, however, be
      asymptomatic. Diagnosis relies on X-ray examination and pathology. Prognosis is
      assessed by X-rays and markers of bone remodelling. Several breakthroughs in the
      understanding of the pathophysiology have been made in the past 10 years. It is
      now recognized that fibrous dysplasia is caused by a somatic activating mutation
      of the Gs alpha subunit of protein G, resulting in an increased cAMP
      concentration and thus in abnormalities of osteoblast differentiation, these
      osteoblasts producing abnormal bone. There is also an increase in interleukin-6
      induced osteoclastic bone resorption, which is the rationale for treating these
      patients with bisphosphonates. In the past 10 years, the bisphosphonate
      pamidronate has been used by infusion for fibrous dysplasia (two courses per
      year), with good results with respect to pain and, in about 50% of patients, the
      refilling of osteolytic lesions.

PMID- 10925750
TI  - Synovial neoformations and tumours.
AB  - An important group of soft tissue tumours and tumour-like lesions originates from
      the synovium of the joints, bursae and tendon sheaths. These include synovial
      chondromatosis, diffuse articular lipomatosis (lipoma arborescens), villonodular
      synovitis, synovial haemangioma, synovial chondroma and fibroma (intracapsular
      and peri-articular), primary chondrosarcoma originating from the synovium and
      synovial sarcoma. The main clinical symptoms of these tumours, such as pain,
      swelling, effusion and joint locking, are not specific, so the diagnosis can
      easily be missed in clinical practice. The most important clinical
      characteristics and the differential diagnostic clues for synovial tumours and
      tumour-like lesions are described in this chapter. In addition, the new results
      of genetic and histological studies are discussed, together with a summary of the
      available evidence-base for therapy.

PMID- 10925752
TI  - Osteonecrosis.
AB  - Osteonecrosis (avascular necrosis, aseptic necrosis or subchondral avascular
      necrosis) is not a specific disease entity but the final common pathway of a
      number of conditions leading to bone death. The main predisposing factors
      (trauma, glucocorticosteroids, alcoholism and connective tissue disorders) should
      be carefully sought, but osteonecrosis can also be idiopathic in origin. Its most
      common localization is to the femoral head, followed by the humeral head, the
      knee and the small bones of the wrist and foot. New imaging techniques,
      especially magnetic resonance imaging, have improved the early diagnosis of
      osteonecrosis as radiographs may be normal in the initial stages. The outcome for
      the patient is influenced by many factors, the size and localization of the bone
      necrosis being of primary importance. Early intervention (both surgical and non
      surgical) has definitively improved the outcome, but still nearly 50% of cases of
      femoral head osteonecrosis necessitate arthroplasty. In this chapter, we shall
      concentrate on patients at high risk of osteonecrosis, on evidence-based
      diagnosis, especially in the early stages, and on evidence-based treatment suited
      to the staging system of osteonecrosis.

PMID- 10925753
TI  - New Canadian hypertension recommendations. So what?

PMID- 10925754
TI  - Nothing to whine about.

PMID- 10925755
TI  - To spank or not to spank.

PMID- 10925756
TI  - New approach to treating Escherichia coli O157:H7?

PMID- 10925757
TI  - Pharmacologic or behavioural therapy for elderly people's insomnia. Which is
      better?

PMID- 10925758
TI  - Queen's University alternative funding plan. Effect on patients, staff, and
      faculty in the Department of Family Medicine.
AB  - OBJECTIVE: To determine the effect of the Queen's University alternative funding
      plan (AFP) on the Department of Family Medicine in terms of patient, staff, and
      faculty satisfaction; patient encounter logistics; clinical volume; and academic
      activity. DESIGN: Before-after study. SETTING: Department of Family Medicine at
      Queen's University of Kingston, Ont. PARTICIPANTS: Patients, faculty, and staff
      of the Department of Family Medicine's Family Medicine Centre. INTERVENTIONS: The
      AFP of Queen's University. MAIN OUTCOME MEASURES: Patient satisfaction, staff and
      faculty job satisfaction, patient waiting time, time spent with patients, patient
      volume, number of publications, and amount of research funding obtained by
      faculty members. These outcomes were measured before the AFP began (time 0), 1
      year post-AFP (time 1), and 2.5 years post-AFP (time 2). RESULTS: In some
      categories patients' satisfaction decreased at time 1, but in all cases it was
      either unchanged or improved at time 2. Staff and faculty job satisfaction did
      not change over time. Patients spent less time in the waiting room at time 2 than
      at time 0. Patient volume dropped about 10% between time 0 and time 2.
      Publication rate did not change, but external research funding increased
      significantly during the study period. CONCLUSION: The AFP has improved academic
      productivity, decreased patient volume by 10%, and improved patient flow during
      clinics. No negative effects on patient satisfaction or on job satisfaction of
      staff or faculty are apparent.

PMID- 10925759
TI  - Falling through the cracks. Women's experiences of ineligibility for genetic
      testing for risk of breast cancer.
AB  - OBJECTIVE: To describe experiences of women seeking information about their risk
      of hereditary breast cancer who fail to meet strict eligibility criteria for
      genetic counseling and testing. DESIGN: Qualitative descriptive study. SETTING:
      Hereditary cancer program in western Canada. PARTICIPANTS: Women who had received
      notification of their ineligibility for referral for hereditary breast cancer
      risk assessment (n = 20) and some of their referring physicians (n = 10). Of 28
      attempted contacts, five women had moved, one declined the invitation to
      participate, and two could not be interviewed because of scheduling conflicts.
      Ten of 20 physicians declined the invitation to participate. METHOD: In-depth,
      open-ended telephone interviews were conducted. Transcribed interviews were
      systematically analyzed to identify salient themes. MAIN FINDINGS: Three themes
      emerged. The first theme, "It's always on your mind," points to the profound
      concern about breast cancer that underlies women's experiences in seeking genetic
      testing. The second theme, "A test is a test," reflects women's beliefs that the
      test was relatively simple and similar to other medical tests in that it would
      provide a definitive answer. The third theme, "Falling through the cracks,"
      captures the experience of ineligibility. Women reacted with a range of emotional
      responses and were left frustrated in their search for more specific information
      about their personal risk for breast cancer. Although women were encouraged to
      contact their physicians, few did. CONCLUSION: These findings point to the
      psychological consequences in women who seek genetic testing for risk of breast
      cancer when they are told they are ineligible and they are not given adequate
      information and support.

PMID- 10925760
TI  - Necrotizing fasciitis secondary to group A streptococcus. Morbidity and mortality
      still high.
AB  - OBJECTIVE: To update physicians on Group A streptococcal necrotizing fasciitis,
      including current methods of diagnosis and treatment. QUALITY OF EVIDENCE:
      Current literature (1990-1998) was searched via MEDLINE using the MeSH headings
      necrotizing fasciitis, toxic shock syndrome, and Streptococcus. Articles were
      selected based on clinical relevance and design. Most were case reports, case
      series, or population-based surveys. There were no randomized controlled trials.
      MAIN MESSAGE: The hallmark of clinical diagnosis of necrotizing fasciitis is pain
      out of proportion to physical findings. Suspicion of underlying soft tissue
      infection should prompt urgent surgical examination. Therapy consists of
      definitive excisional surgical debridement in conjunction with high-dose
      intravenous penicillin G and clindamicin. Risk factors for mortality include
      advanced age, underlying illness, hypotension, and bacteremia. CONCLUSION:
      Necrotizing soft tissue infections due to Group A streptococcus might be
      increasing in frequency and aggression. Overall mortality remains high (20% to
      34% in larger series). Clinical diagnosis requires a high level of suspicion and
      should prompt urgent surgical referral.

PMID- 10925761
TI  - Practical management of hair loss.
AB  - OBJECTIVE: To describe an organized diagnostic approach for both nonscarring and
      scarring alopecias to help family physicians establish an accurate in-office
      diagnosis. To explain when ancillary laboratory workup is necessary to confirm
      the diagnosis. QUALITY OF EVIDENCE: Current diagnostic and therapeutic
      interventions for hair loss are based on randomized controlled studies,
      uncontrolled studies, and case series. MEDLINE was searched from January 1966 to
      December 1998 with the MeSH words alopecia, hair, and alopecia areata. Articles
      were selected on the basis of experimental design, with priority given to the
      most current large multicentre controlled studies. Overall global evidence for
      therapeutic intervention for hair loss is quite strong. MAIN MESSAGE: The most
      common forms of nonscarring alopecias are androgenic alopecia, telogen effluvium,
      and alopecia areata. Other disorders include trichotillomania, traction alopecia,
      tinea capitis, and hair shaft abnormalities. Scarring alopecia is caused by
      trauma, infections, discoid lupus erythematosus, or lichen planus. Key to
      establishing an accurate diagnosis is a detailed history, including medication
      use, systemic illnesses, endocrine dysfunction, hair-care practices, and family
      history. All hair-bearing sites should be examined. A 4-mm punch biopsy of the
      scalp is useful, particularly to diagnose scarring alopecias. Once a diagnosis
      has been established, specific therapy can be initiated. CONCLUSIONS: Diagnosis
      and management of hair loss is an interesting challenge for family physicians. An
      organized approach to recognizing characteristic differential features of hair
      loss disorders is key to diagnosis and management.

PMID- 10925763
TI  - Rapid HIV screening. "We must prevent potential misuses".

PMID- 10925762
TI  - Diagnosis and treatment of high blood pressure. New directions and new
      approaches: 1999 Canadian recommendations for management of hypertension.

PMID- 10925764
TI  - Understanding reentry to out-of-home care for reunified infants.
AB  - Although many children placed in out-of-home care are reunified with their
      families of origin, a significant portion reenter care, reflecting continued
      family problems and weaknesses within the child welfare system. For infants, the
      stability of reunification is particularly crucial, given their developmental
      stage. This study reviewed the case records of 88 randomly selected infants who
      had been reunified with their families. Thirty-two percent of those infants
      reentered care within four to six years of their reunification. The
      identification of factors predictive of reentry into care has both policy and
      practice implications.

PMID- 10925765
TI  - The role of friends, in-laws, and other kin in father-perpetrated child physical
      abuse.
AB  - Thirty-five physically abusive fathers were matched with a comparison sample to
      test multiple systemic explanations for child physical abuse, using an ecological
      perspective, and to show the relationship between the structure of social ties
      and the function of those ties. The physically abusive fathers were found to have
      received significantly fewer emotional and instrumental supports from their
      friends, in-laws, and other kin than the comparison fathers, and were only weakly
      linked to members of their social networks--members who might have discouraged
      the fathers' aggressive impulses or provided additional support to them and to
      their families.

PMID- 10925766
TI  - Toward building a typology for the evaluation of services in family support
      programs.
AB  - This article briefly reviews the history, philosophy, practice principles, and
      foci of family support programs, examines the typologies currently in use to
      classify these programs, and discusses the difficulties these classifications
      pose for program evaluators. The authors introduce a new typology that
      deconstructs family support programs into their component services and discuss
      the potential of this typology for evaluation of family support services.

PMID- 10925767
TI  - The role of medication and sugars in pediatric dental patients.
AB  - It is now widely accepted that sugar-containing medicines are a cause of dental
      caries in chronically sick children. The increase of prescribed medicine intake
      and of self-medication in developed countries exposes a growing number of
      children to medication caries, which can be considered a public health problem.
      Health workers should first of all be informed. The second step consists of
      involving each country's institutional structures in charge of public health to
      ensure that they modify the legislation on medicine manufacture and sale,
      following the exemplary action of Great Britain. The third step is to pressurize
      manufacturers so that they decide to produce all liquid pediatric medicine in
      sugared and nonsugared forms. This step can be accomplished only if prescribers
      preferentially prescribe sugar free medicines and promote sugar free medicines to
      their patients.

PMID- 10925768
TI  - Craniofacial growth.
AB  - Craniofacial growth represents a complex enlargement and differentiation of hard
      and soft tissues, characterized by cephalocaudal and allometric patterns. The
      cranial base matures earlier than the face and is used cephalometrically as a
      relatively stable reference area. The maxilla, although intimately associated
      with the cranium, exhibits some independent growth, particularly in the vertical
      dimension. The mandible, hanging in a sling of muscles and articulating only at
      the temporomandibular fossae and with the opposing dentition, is purportedly able
      to adapt its shape and position in space to some extent as a function of condylar
      growth.

PMID- 10925769
TI  - Behavior management of children in the dental office.
AB  - One of the first conclusions offered by this article was that behavior management
      has been a pertinent theme in literature addressing clinical pediatric dentistry.
      This has been true for much of the twentieth century. Another conclusion stated
      that this literature generally focuses on the preschool child after the child has
      acquired sufficient development and maturity that he or she can be communicated
      to in conversation. It was also pointed out that most general approaches to the
      subject of behavior management deal with the normal child, which for the purposes
      of this article can be construed as a cognitively, sociologically, and
      psychologically developed child with no unusual circumstances. The usual age of a
      child being approachable in language was determined to be approximately around
      the third birthday. An analysis of patient management in two previous issues of
      Dental Clinics of North America written almost 35 years apart revealed that there
      were many more similarities than differences. One conclusion derived from the
      present article was that all North American dental practitioners have lived in a
      culture that assumed that the behavior management of normal children 3 years of
      age and older can generally be regarded as achievable through linguistic
      techniques. This comparison of the two issues showed that the topics of informed
      consent and risk management in behavioral pediatric dentistry grew considerably
      in the last decades of the twentieth century, pharmacologic techniques became
      more sophisticated, and the linguistic domain remained important to most dentists
      who sought to treat preschool children. Regarding this last point, it was offered
      that a lot of the success of a clinician within the linguistic domain may be
      determined as much by the thoughts, feelings, and nonverbal acts of communication
      of the clinician as by any other factor. These include the many factors that
      describe a child's possibilities of success during the dental experience, such as
      fear status, allegiance to a misdirected goal of childhood, and learned
      helplessness. Because of the importance of the linguistic domain to most
      practitioners treating children, this domain was focused on, including how
      further mastery might be obtained for the clinician seeking more competence here.
      A method of the clinician examining his or her own effectiveness to refine a
      strategy for addressing the potential for more powerful linguistic interactions
      with children was briefly outlined. For the practitioner wishing more specific
      information, the reference list should provide a didactic base for further
      intellectual distinctions and assessments.

PMID- 10925770
TI  - Infant oral health.
AB  - According to the United Nations' Convention on "The Rights of the Child,"
      articles 2 and 24, all children should have the same rights and have right to
      health and medical service. Early childhood caries is a lifestyle disease with
      biologic, behavioral, and social determinants. An early screening of all children
      at around 1 year of age is an excellent opportunity for early detection of risk
      factors and risk indicators that may increase the possibilities for its
      prevention. The caries risk evaluation should form the base for appropriate
      recommendations of preventive measures. The preventive care must be coordinated
      with an eventual operative care and should be based on education of prospective
      and new parents as well as professional and home-based measures. The various
      interventions must be developed further and evaluated in prospective studies in
      terms of effectiveness and efficiency for this specific age group. This is an
      urgent task for dental professionals and all societies with the ambition of
      providing good dental care for all young children.

PMID- 10925771
TI  - Principles of diagnosis and treatment of high-caries-risk subjects.
AB  - The aim of this article is to highlight the main goals and to describe the
      clinical impact of the procedures used for the identification of high-caries-risk
      subjects. The techniques for the correction of caries risk level and their
      influence on restorative treatment are also described to enable the dental team
      to offer patients the most appropriate and successful treatment, and to meet an
      up-to-date and high-quality dental care standard.

PMID- 10925772
TI  - Resin-based composites and compomers in primary molars.
AB  - Resin-based composite resins and polyacid-modified resin-based composites
      (compomers) have become popular for the restoration of primary anterior and
      posterior teeth. In some European countries, resin-based composites or glass
      ionomers are the materials of choice for primary teeth because of the controversy
      over dental amalgam and its alleged adverse health effects resulting from the
      release of mercury, although a clear correlation between amalgam restorations and
      health has not been determined. Another reason for the worldwide increased use of
      resin-based composites and glass-ionomers in pediatric dentistry could be
      attributed to the growing demand from parents to provide esthetic restorations to
      their children. More conservative preparations can be performed maintaining more
      tooth structure because of the adhesive properties of the composites and
      compomers. The most conservative treatment planning and meticulous care in the
      placement of the resin-based composites and compomers would produce long-term
      satisfactory results. These restorations should be placed in patients with low-to
      moderate caries risk, and after placement the restorations should be monitored
      carefully to avoid complications mainly produced by recurrent caries and wear.

PMID- 10925773
TI  - Pulp therapy for the primary and young permanent dentitions.
AB  - This article describes the pulp reactions to caries and operative procedures and
      emphasizes the importance of a clinical diagnosis to evaluate the most
      appropriate pulp treatment. Conservative and radical treatments are described,
      stressing the differences between primary and young permanent dentitions.

PMID- 10925774
TI  - Treatment of trauma to the primary and young permanent dentitions.
AB  - An overview of the various possibilities for trauma to the primary and young
      permanent dentition has been presented. Appropriate treatment procedures have
      been described. Advances in dental science have been great, and dental materials
      have become superior to what they were just a few years ago. The dentist must
      never forget the variabilities of human responses to any of the treatment
      techniques, however, and the dentist must never be dogmatic in approach. The
      dentist should be able to diagnose, interpret, and alter any of the treatment
      techniques as more scientific evidence is obtained.

PMID- 10925776
TI  - The evaluation and treatment of pediatric oral habits.
AB  - Oral habits continue to be a common problem in pediatric dentistry. This article
      briefly describes the most common oral habits and presents treatment options for
      resulting problems.

PMID- 10925775
TI  - Periodontal diseases in children and adolescents.
AB  - The predominant form of periodontal disease in children and adolescents is
      gingivitis, which is a nonspecific inflammatory reaction of the marginal gingiva.
      The inflammatory reaction in the tissue, initiated by dental plaque accumulation,
      starts early during infancy and reflects the bacterial challenge to the host. In
      most children, the process of gingival inflammation remains superficial. In some
      cases, however, the balance between the microbial challenge and the host response
      is disrupted, leading to an inflammatory process that may result in loss of
      attachment. Genetic factors that modify the host response to the bacterial
      challenge are major determinants of susceptibility to the development of EOP, and
      many systemic diseases have been reported to predispose children and adolescents
      to periodontal disease. It is important to take a complete medical history of the
      patient and assess if there is a hereditary trend for periodontitis within the
      family. Dental professionals should rely on clinical and radiographic criteria of
      the disease for early identification of children at risk, with special focus on
      the presence of subgingival calculus. Children with overt gingival inflammation,
      subgingival calculus, or early signs of alveolar bone loss should be considered
      as periodontitis-risk patients and should be included in a preventive program as
      early as possible.

PMID- 10925777
TI  - Treatment approaches to common symptomatic oral lesions in children.
AB  - A variety of oral mucosal lesions can be symptomatic in children. This article
      describes the classic clinical appearance of the most common oral diseases and
      provides treatment recommendations that are tailored to the pediatric age group.
      When possible, more than one drug alternative is given for each of the different
      oral conditions for an improved success rate. It is essential for the clinician
      to understand that this article should be used as a guide for managing oral and
      perioral lesions in children and adolescents. Specific dosages and formularies of
      drugs may require modification in the young child. Consultation with a primary
      care physician and pharmacist often is needed to ensure the best possible
      outcome, especially when immunosuppressive drugs are indicated. Most importantly,
      oral lesions that do not respond to therapeutic protocols should be referred to
      the appropriate specialist for definitive diagnosis and treatment.

PMID- 10925778
TI  - Practice management in pediatric dentistry.
AB  - Good practice management in the pediatric dental office is not piecemeal,
      sporadic, or a series of random, uncoordinated activities. Instead, it
      encompasses the philosophy of the practice; is centered around the patient; and
      is a fluid, consistent management function. It begins with the pediatric dentist
      as the leader and continues in all phases of daily activity. It is a well
      developed, highly functioning system. It results in staff and patient loyalty and
      high patient satisfaction. It is an ongoing, continuously active, evolutionary
      process. It permits a positive attitude of professional growth for the entire
      pediatric dental staff team.

PMID- 10925779
TI  - Peritumoral administration of antigen-unstimulated bone marrow-derived dendritic
      cells inhibits tumour growth.
AB  - Murine BM cells from B6 mice were grown in vitro in medium supplemented with GM
      CSF and IL-4 to differentiate DC from DC precursors. After 10 days of culture,
      approximately 20% of the cell population exhibited the characteristic morphology
      of BMDC. In cytofluorometric analysis the morphological changes of cells were
      accompanied by upregulation of the expression of the MHC class II, CD11c, CD80,
      and CD86 molecules. The BMDC were pulsed with a lysate of syngeneic MK16
      carcinoma cells and used for in vitro activation of SC. Co-cultivation of the
      carcinoma lysate-pulsed BMDC with SC induced a proliferative response of the
      syngeneic SC. Priming of the proliferative responses was more efficient when the
      BMDC were grown in the presence of GM-CSF and IL-4 for 10 days than for 7 days.
      The in vivo effect of mature, tumour lysate-unstimulated BMDC was examined in
      mice carrying syngeneic MK16 carcinoma transplants. It has been found that local
      pretreatment with BMDC inhibits growth of a subsequent challenge inoculum of the
      MK16 cells. Similarly, treatment of mice carrying small MK16 tumours and of those
      with MK16 surgical minimal residual disease performed with BMDC significantly
      inhibited tumour growth. It can be concluded from these results that local
      concentration of mature BMDC at the tumour site can control the development and
      growth of the transplanted tumour inoculum.

PMID- 10925780
TI  - Rat inbred PD/cub strain as a model of dyslipidemia and insulin resistance.
AB  - Genome scan and metabolic profile of the PD/Cub rat inbred strain in comparison
      with SHR and BN strains is presented. The PD/Cub strain has been bred by brother
      sister mating for more than 60 generations since 1969. Its highly inbred status
      has been confirmed by PCR genotyping with more than 170 microsatellite markers.
      No case of residual heterozygosity has been recorded. Accordingly, the values
      obtained by the analysis of metabolic phenotypes are homogeneous with low
      variance. The PD/Cub strain has significantly higher triglyceride levels and
      epididymal fat weight as compared to both SHR and BN strains. The PD strain also
      displays the lowest incorporation of 14C-U glucose into the epididymal adipose
      tissue. The data on glucose metabolism clearly indicate that the PD/Cub strain is
      insulin resistant. Genetic homogeneity and reproducibility of experimental
      results qualify the PD/Cub rats as an animal model for analysis of the syndrome
      X.

PMID- 10925781
TI  - Perichondrial chondrogenesis and periosteal osteogenesis by localized graft-vs
      host reaction in mice.
AB  - Localized GvH reaction produced by the subcutaneous injection of parental
      lymphoid cells into the ear lobe of F1 recipient mice results in local activation
      of perichondrial chondrogenesis. Similarly, when the GvH reaction was elicited in
      shanks, the periosteal membranes at the site of immune reaction were stimulated
      to proliferate and to produce new bone. However, syngeneic lymphocytes activated
      in vivo by Con A and untreated syngeneic spleen and bone marrow cells
      administered locally produced similar response of bone and cartilage. Thus the
      lymphocytes activated either in the course of GvH reaction or syngeneic
      lymphocytes grafted into heterotopic sites presumably release mediators capable
      to stimulate periosteal/perichondrial membranes.

PMID- 10925782
TI  - Synthetic hydrogel capacity to induce formation of foreign-body giant
      multinucleate cells differs in vivo and in vitro.
AB  - The granulomatous reaction accompanied with MGC formation represents the most
      striking feature of the non-favourable biological tolerance of implanted devices.
      We compared MGC formation in the course of the granulomatous reaction in vitro
      and in vivo employing three types of hydrogels whose biocompatibility had been
      well studied earlier. The efficiency of the in vitro assay for the granulomatous
      reaction, including MGC formation, was verified employing the nematode
      Nippostrongylus brasiliensis, a well-known inductor of MGC formation in vitro.
      The in vitro results demonstrated a very low level of MGC formation in reaction
      against all three types of hydrogels without polymer-specific differences in
      comparison with the nematode experiment characterized by a high extent of MGC
      formation. On the other hand, the extent of MGC formation was implant type
      specific in vivo: pHEMA-co-DMAEMA > pHEMA > pHEMA-co-NaMA. These results indicate
      that in the in vitro assay it was not possible to discriminate among the types of
      polymers used in the experiment in comparison with the animal experiment. They
      also indicate potential differences between granuloma formation induced by
      parasites and by foreign bodies.

PMID- 10925783
TI  - Phenotype, immunological reactivity and cytokine production profile of Peyer's
      patch cells from mice immunized orally with allogeneic cells.
AB  - Mice of inbred strain BALB/c were immunized orally for 10 consecutive days with
      fresh spleen cells from allogeneic C57BL/10 (B10) donors. The immunized mice
      displayed significant allotransplantation immunity in vivo as demonstrated by
      resistance to the growth of allogeneic tumours induced by high doses of tumour
      cells. No significant changes in the proportion of the major T cell subsets in PP
      of immunized mice were found 1 or 7 days after the last immunization dose.
      However, PP cells from orally immunized mice displayed stronger proliferative
      response after stimulation with cells used for oral immunization than the cells
      from control animals. Similarly, after stimulation in vitro with specific
      alloantigens, PP cells from orally immunized mice produced more IFN-gamma than
      the cells from control recipients. On the contrary, the production of IL-4 was
      significantly decreased in the immunized mice. The production of IL-2 by PP cells
      after oral immunization was not significantly changed and IL-10 was only slightly
      increased. The results thus show that oral immunization with allogeneic cells
      induces systemic transplantation immunity which can be demonstrated already in
      Peyer's patches by increased cell proliferation after immunization with specific
      alloantigens and by changes in cytokine production.

PMID- 10925784
TI  - Novel point mutations in mitochondrial 16S rRNA gene of Chinese hamster cells.
AB  - To know the nature and mechanisms of spontaneous mutations in mitochondrial DNA
      (mtDNA), we determined, by direct cycle sequencing, the nucleotide sequence of
      the 3' terminal region of the mitochondrial 16S rRNA gene from chloramphenicol
      resistant (CAP-R) mutants isolated in Chinese hamster V79 cells. Four different
      base substitutions were identified in common for the six CAP-R mutants. All
      mutations were heteroplasmic. One A to G transition was mapped at a site within
      the putative peptidyl transferase domain, the target region for chloramphenicol,
      and one G to A transition and two T to G transversions were located within the
      two different segments which form the stems of the hairpin loop structures
      attached to this key domain in the predicted secondary structure of 16S rRNA. The
      mutations detected in this study do not map to the same sites where CAP-R
      mutations were found previously in mammalian cells. Allele specific-PCR analyses
      revealed that all four mutations occurred on a single mutant-DNA molecule, but
      not on several ones independently. Together with the other previous reports, our
      data suggest that spontaneous mtDNA mutations may not be caused exclusively by
      oxidative DNA damage at least in 16S rRNA gene.

PMID- 10925785
TI  - New transposable elements identified as insertions in rice transposon Tnr1.
AB  - Tnr1 (235 bp long) is a transposable element in rice. Polymerase chain reactions
      (PCRs) done with a primer(s) that hybridizes to terminal inverted repeat
      sequences (TIRs) of Tnr1 detected new Tnr1 members with one or two insertions in
      rice genomes. Six identified insertion sequences (Tnr4, Tnr5, Tnr11, Tnr12, Tnr13
      and RIRE9) did not have extensive homology to known transposable elements, rather
      they had structural features characteristic of transposable elements. Tnr4 (1767
      bp long) had imperfect 64-bp TIRs and appeared to generate duplication of a 9-bp
      sequence at the target site. However, the TIR sequences were not homologous to
      those of known transposable elements, indicative that Tnr4 is a new transposable
      element. Tnr5 (209 bp long) had imperfect 46-bp TIRs and appeared to generate
      duplication of sequence TTA like that of some elements of the Tourist family.
      Tnr11 (811 bp long) had 73-bp TIRs with significant homology to those of Tnr1 and
      Stowaway and appeared to generate duplication of sequence TA, indicative that
      Tnr11 is a transposable element of the Tnr1/Stowaway family. Tnr12 (2426 bp long)
      carried perfect 9-bp TIRs, which began with 5'-CACTA- -3' from both ends and
      appeared to generate duplication of a 3-bp target sequence, indicative that Tnr12
      is a transposable element of the En/Spm family. Tnr13 (347 bp long) had 31-bp
      TIRs and appeared to generate duplication of an 8-bp target sequence. Two
      sequences, one the transposon-like element Crackle, had partial homology in the
      Tnr13 ends. All five insertions appear to be defective elements derived from
      autonomous ones encoding the transposase gene. All had characteristic tandem
      repeat sequences which may be recognized by transposase. The sixth insertion
      sequence, named RIRE9 (3852 bp long), which begins with 5'-TG- -3' and ends with
      5'- -CA-3', appeared to generate duplication of a 5-bp target sequence. These and
      other structural features indicate that this insertion is a solo LTR (long
      terminal repeat) of a retrotransposon. The transposable elements described above
      could be identified as insertions into Tnr1, which do not deleteriously affect
      the growth of rice cells.

PMID- 10925786
TI  - Sequence variation and structural conservation in the D-loop region and flanking
      genes of mitochondrial DNA from Japanese pond frogs.
AB  - The nucleotide sequences of the D-loop region and its flanking genes of the
      mitochondrial DNA (mtDNA) from Japanese pond frogs were determined by the methods
      of PCR, cloning, and sequencing. The frogs belonged to two species, one
      subspecies, and one local race. The gene arrangements adjacent to the D-loop
      region were analyzed. The frogs shared a unique mitochondrial gene order that was
      found in Rana catesbeiana; i.e., cyt b--D-loop region--tRNA(Leu(CUN))--tRNA(Thr)-
      tRNA(Pro)--tRNA(Phe)--12S rRNA. The arrangements of the three tRNA genes of these
      frogs were different from those of X. laevis, a species which has the same
      overall structure as in mammals. Highly repetitive sequences with repeat units
      (16-bp or 17-bp sequence specific for each taxon) were found in the D-loop
      region. The length of repetitive sequences varied from 0.6 kbp to 1.2 kbp, and
      caused the extensive size variation in mtDNA. Several short sequence elements
      such as putative TAS, OH, CSB-1, and CSB-2 were found in the D-loop region of
      these frogs. The sequences of these short regulatory elements were conserved in
      R. catesbeiana, X. laevis, and also in human. The comparison of sequence
      divergences of the D-loop region and its adjacent genes among various taxa
      revealed that the rates of nucleotide substitutions depend on genes. The
      nucleotide sequences of the 3'-side segment of the D-loop region were the most
      variable among taxa, whereas those of the tRNA and 12S rRNA genes were the most
      conservative.

PMID- 10925787
TI  - Identification and genetic mapping of RAPD markers linked to the densonucleosis
      refractoriness gene, nsd-2, in the silkworm, Bombyx mori.
AB  - In the silkworm, Bombyx mori, nonsusceptibility to B. mori densonucleosis virus
      type-2 (BmDNV-2) is controlled by a recessive gene, nsd-2 (nonsusceptibility to
      DNV-2). We investigated the genetic linkage between two random-amplified
      polymorphic DNA (RAPD) markers and the +nsd-2 gene. Initially, we constructed the
      JSD-2 strain (nsd-2/+), which is congenic to strain J137 (nsd-2/nsd-2) with
      respect to the chromosome containing the +nsd-2 gene, starting with a female of
      strain J137 and a male of strain C137 (+nsd-2/+nsd-2). Genomic DNAs were compared
      between infected individuals of the JSD-2 strain and J137 by a polymerase chain
      reaction (PCR) with 700 arbitrary 10-mer primers. Two RAPD markers (OPH19R and
      OPP01R) linked to the +nsd-2 gene were found. For the crossing-over experiment, a
      female of J137 was crossed with a male (nsd-2/+) of JSD-2. Segregation analysis
      showed that the most closely linked RAPD marker (OPP01R) was mapped 4.7 cM
      distant from +nsd-2.

PMID- 10925788
TI  - Seasonal fluctuation in susceptibility to insecticides within natural populations
      of Drosophila melanogaster: empirical observations of fitness costs of
      insecticide resistance.
AB  - To investigate genetic variation and seasonal fluctuation in susceptibility to
      insecticides, natural populations of Drosophila melanogaster were collected from
      Katsunuma in mid summer and late fall for two consecutive years. After isofemale
      lines of each population collected in each season had been established in a
      laboratory, the susceptibility of each line to five insecticides, including
      permethrin, malathion, prothiophos, fenitrothion, and DDT, was examined. Lines of
      each population exhibited the broad ranges of variation in susceptibility to all
      chemicals. Comparison between populations in different seasons indicated that
      genetic variation in susceptibility to organophosphates fluctuated in consistency
      with the population size, in which the susceptibility increased in fall. In
      addition, highly significant correlations were observed among responses to
      organophosphates, and the correlations also fluctuated with seasons. On the other
      hand, genetic variation in susceptibility to permethrin and DDT was less
      fluctuated. These results suggest that not only a common resistance factor for
      organophosphate resistance but also different resistance factor(s) for each
      insecticide could be involved within a natural population, and that the
      fluctuation observed in the susceptibility to organophosphates could be
      associated with fitness costs of organophosphate resistance factor(s).

PMID- 10925789
TI  - Characterization of early follicular cDNA library suggests evidence for genetic
      polymorphisms in the inbred strain C108 of Bombyx mori.
AB  - Recent work towards the completion of a saturated molecular genetic linkage map
      for the lepidopteran silkworm, Bombyx mori (n = 28), has provided evidence for
      existing polymorphisms in the inbred strain C108. Two inbred parental strains,
      p50 and C108, were crossed to produce the F1 (P/C) hybrid offspring. The
      populations used in this project were comprised of a combination of 29 F2 (F1 x
      F1) and 31 reciprocal backcross (P/C x C/C, P/C x P/P) progeny. All restriction
      fragment length polymorphisms (RFLPs) for the initial analysis were hybridized
      with anonymous probes derived from a random early follicular cDNA (Rcf) library
      from Bombyx. A total of 19 Rcf probes were selected as showing scorable
      codominant polymorphic patterns when screened against F2 and backcross DNAs
      digested with the restriction enzymes EcoRI, HindIII, or PstI, and Southern
      blotted to nylon membranes for hybridization. Of the newly reported Rcf probes, 7
      (37%) were characterized as producing 'simple' polymorphic patterns, while 12
      (63%) were characterized as producing 'complex' polymorphic patterns. Further
      characterization of the complex patterns subdivided this group into two general
      classes: polymorphisms that contained an additional allele, and multiple bands
      that contained an easily scored two banded polymorphism. Because the extra allele
      class was limited to the (P/C x C/C) backcross progeny, it is suggested that the
      inbred parental strain C108 harbors polymorphic loci that are inherited in a
      simple Mendelian fashion. A genetic analysis discussing plausible origins and
      maintenance of these polymorphisms is presented.

PMID- 10925790
TI  - High frequency of microsatellites in Drosophila pseudoobscura.
AB  - Using 30,000 bp of anonymous sequence data, we note that dinucleotide repeat
      arrays appear to be much more common in Drosophila pseudoobscura than in D.
      melanogaster or D. simulans. Repeat arrays bearing five or more units are
      situated on average once every 3000 bp in D. pseudoobscura, and repeat arrays
      bearing ten or more units are situated on average once every 7500 bp. We did not
      detect an association between microsatellite presence and GC-content of flanking
      regions.

PMID- 10925791
TI  - Copepod predation on Anopheles quadrimaculatus larvae in rice fields.
AB  - Cyclopoid copepods and mosquito larvae were surveyed in southwestern Louisiana
      rice fields. Almost every rice field had a natural population of Mesocyclops
      ruttneri, Acanthocylops vernalis, or Macrocyclops albidus. Judging from the
      abundance of pupae, 29% of the fields were responsible for virtually all
      Anopheles quadrimaculatus production, apparently because larval mortality
      suppressed production in the other fields. Mesocyclops ruttneri had the strongest
      negative association of naturally occurring copepod populations with An.
      quadrimaculatus larvae, though a few fields with M. ruttneri had substantial
      Anopheles production. Macrocyclops albidus, M. ruttneri, Mesocyclops edax, and
      Mesocyclops longisetus were introduced to experimental rice field plots. It took
      two months for the introduced copepods to build up their numbers; Anopheles
      larvae then disappeared from all treated plots while larvae continued to be
      present in the adjacent control field. Copepods were observed to kill the
      following number of first instar An. quadrimaculatus larvae in the laboratory:
      Mesocyclops ruttneri (36 larvae/day), Macrocyclops albidus (23 larvae/day),
      Mesocyclops longisetus (24 larvae/day), and Acanthocyclops vernalis (15
      larvae/day). It is concluded that introducing select species of copepods and
      encouraging their populations offer possibilities for contributing to Anopheles
      control in rice fields.

PMID- 10925792
TI  - Natural control of Culex quinquefasciatus larvae in residential ditches by the
      copepod Macrocyclops albidus.
AB  - Natural populations of three larvivorous copepod species live in residential
      roadside ditches in Louisiana: Macrocyclops albidus, Acanthocyclops vernalis, and
      Megacyclops latipes. Macrocyclops is most common and killed an average of 27
      first-instar Culex quinquefasciatus larvae/copepod/day in the laboratory.
      Although severe pollution from septic tank effluent in some parts of the ditches
      creates havens for Cx. quinquefasciatus production by excluding predatory
      copepods and fish (Gambusia affinis), Macrocyclops and the fish substantially
      reduce Cx. quinquefasciatus larval survival when present where pollution is not
      so severe. At natural abundance, Macrocyclops reduced the survival of Cx.
      quinquefasciatus larvae (during their first four days) to 2.6%, compared with 46%
      survival in controls without Macrocyclops. During one year of field observation,
      Macrocyclops was common in the spring but disappeared during the summer when fish
      (which prey on copepods) appeared in many ditches, reduced water flows led to
      more severe pollution, and water temperatures in very shallow water were
      sometimes higher than Macrocyclops could survive. Macrocyclops reappeared in many
      ditches during autumn and winter, when water temperatures and pollution declined
      and fish disappeared. Introduction of Macrocyclops to ditches in October
      accelerated its reappearance during autumn and winter and reduced the number of
      sites with Cx. quinquefasciatus larvae to one-quarter the number in control
      ditches. The most effective way to control Cx. quinquefasciatus is to eliminate
      pollution so predators like fish and copepods can live throughout the ditches,
      but timely introduction of fish and copepods could also contribute to control.
      More experience will be necessary to ascertain whether copepod introductions are
      cost effective.

PMID- 10925793
TI  - A mark-release-recapture study on the spatial distribution of host-seeking
      anophelines in northern Thailand.
AB  - A mark-release-recapture experiment was conducted at Mae Taeng, Chiangmai,
      Thailand, in November 1990 to examine the movement of released host-seeking
      mosquitoes in a heterogeneous environment. A total of 1,848 mosquitoes of nine
      anopheline species was field-collected, marked with fluorescent dye, and
      released. Adult collections were made for four nights after the release at five
      collection sites surrounding the release site. Three different attractants, dry
      ice (5 kg/site/night), human, and cow bait were used to collect a large number
      and a wide variety of adult mosquitoes. The recapture rate of released mosquitoes
      differed among species, ranging from 0 to 7.5%. The species composition was
      significantly different among collection sites and collection methods, and
      samples from dry ice collection showed intermediate species composition between
      those from human and cow bait collections. The spatial distribution of released
      mosquitoes was not significantly different from that of unmarked mosquitoes.
      Different behavioral responses to heterogeneous environments by different species
      of host-seeking mosquitoes was suggested as the underlying mechanism of species
      specific spatial distribution of mosquitoes in the study area.

PMID- 10925794
TI  - Winter ectoparasites of mammals in the northeastern piedmont area of Georgia.
AB  - Twenty-three species of ectoparasites were recovered from 10 species of mammals
      (89 individuals) in Mistletoe State Park, Columbia County, Georgia, during three
      winter months of 1998. The collection consisted of 9 species of fleas, 6 mites, 4
      sucking lice, 3 ticks, and 1 mammal-associated beetle. Some rarely-collected
      arthropods were recorded including the ctenophthalmid fleas, Doratopsylla
      blarinae C. Fox and Epitedia cavernicola Traub, the laelapid mite, Echinonyssus
      blarinae (Herrin) (first records from Georgia for these three ectoparasites), and
      the leptinid beetle, Leptinus orientamericanus Peck (second record for Georgia).
      Varying degrees of host-specificity were exhibited by the 23 species of
      ectoparasites. Because relatively few mammal ectoparasite surveys are completed
      during the winter months, some seemingly rare species may, in reality, be more
      common at this time of year.

PMID- 10925795
TI  - Use of water drums by humans and Aedes aegypti in Trinidad.
AB  - This report documents the results of a countrywide survey by county for Aedes
      aegypti (L.) mosquitoes found breeding in drums in Trinidad, West Indies. The
      island-wide mean number of positive drums was 8.1 +/- 2.9 per county and the mean
      number of positive drums per house was 3.0 +/- 0.7 and ranged from 1.6 in St.
      George East to 4.9 in St. Andrew/St. David. The Breteau index varied from 6.2 in
      St. Andrew/St. David to 52.5 in Victoria East, with the median figure of 29.5.
      The most common location of drums was under the eaves of houses (71.4%) in eight
      out of nine counties surveyed, and a high proportion (82.3%) was positive for Ae.
      aegypti at this location. Water stored in drums was used primarily for washing
      clothing (57.5%), with 6.6% for drinking, 12.9% for bathing, and 23.0% for
      miscellaneous purposes. An average of 68.4% of all drums at the nine sites were
      uncovered and were located under the eaves of houses, with 76.2% being filled
      under the eaves by rainfall. Tanks were the main potable water storage container
      found in all nine counties, with a mean number of 1.4 +/- 0.6 per county. In our
      survey, all water drums were treated as if they were for potable use, but this
      had virtually no correspondence with the actual findings in each county per
      household. We conclude that vector control strategies based on insecticide
      treatment and source reduction need to be revised in light of the current
      findings.

PMID- 10925796
TI  - Susceptibility of geographically distinct Aedes aegypti L. from Florida to
      Dirofilaria immitis (Leidy) infection.
AB  - In the present study, five geographically distinct populations of Aedes aegypti
      L. from various regions of Florida were compared for their susceptibilities to
      Dirofilaria immitis (Leidy) infection. The populations were from Gainesville
      (North Central), Jacksonville (North Eastern), Naples (South Western), Sarasota
      (West Central), and Vero Beach (East Central). Mosquitoes of all the populations
      had fewer parasites in their Malpighian tubules 6 and 13 days after blood feeding
      compared to the number of microfilariae initially ingested. There was no
      significant difference in the mean number of the total parasites per female 6 and
      13 days after taking an infectious blood meal. In comparison, significantly
      larger numbers of the microfilariae completed development in the laboratory
      selected Vero Beach susceptible strain. Females excreted microfilariae within 72
      hr. of engorgement on an infected dog and the Gainesville, Jacksonville, Naples,
      and Sarasota populations had 20-23% females that lacked ovarian development six
      days after blood feeding. Out of these, in 16-22% of the females from the
      Jacksonville, Naples, and Sarasota populations, parasite development was arrested
      mostly as moribund prelarvae and only few developing larvae were observed. All
      females of the Gainesville population that did not develop eggs (20%) also lacked
      parasites. In the Jacksonville population, 23% of the females that matured eggs
      had no infection. Eight percent of the females from the Sarasota population
      exhibited a similar response. Low survivorship was observed at 6 and 13 days
      after imbibing an infectious blood meal. Females showed melanization of
      microfilariae in the Malpighian tubules, on the midgut wall, and in the hemocoel.
      Cellular melanization response was observed in the hemocoel, whereas, a humoral
      melanization response was observed in the Malpighian tubules. The Vero Beach
      susceptible strain showed maximum vector efficiency and lowest survival at 13
      days post-blood meal compared to the Jacksonville and the Gainesville
      populations.

PMID- 10925797
TI  - A probability model of vector behavior: effects of DDT repellency, irritancy, and
      toxicity in malaria control.
AB  - A probability model of how DDT residues may function within a malaria control
      program is described. A step-wise organization of endophagic behaviors culminates
      in a vector acquiring a human blood meal inside the house. Different vector
      behaviors are described, epidemiologically defined, temporally sequenced, and
      quantified with field data. Components of vector behavior and the repellent,
      irritant, and toxic actions of insecticide residues are then assembled into a
      probability model. The sequence of host-seeking behaviors is used to partition
      the total impact of sprayed walls according to the three chemical actions.
      Quantitatively, the combined effect of repellency and irritancy exert the
      dominant actions of DDT residues in reducing man-vector contact inside of houses.
      These relationships are demonstrated with published and unpublished data for two
      separate populations of Anopheles darlingi, for Anopheles gambiae and Anopheles
      funestus in Tanzania, and Anopheles punctulatus in New Guinea.

PMID- 10925798
TI  - A comparison study of house entering and exiting behavior of Anopheles
      vestitipennis (Diptera: Culicidae) using experimental huts sprayed with DDT or
      deltamethrin in the southern district of Toledo, Belize, C.A.
AB  - An investigation of the house entering and exiting behavior of Anopheles
      vestitipennis Dyar and Knab was undertaken in the Toledo District of Belize,
      Central America, between March and December of 1998. Three untreated experimental
      huts were either fitted with exit or entrance interception traps or used as a
      control for human landing collections. Human landing collections showed that An.
      vestitipennis exhibited a high level of biting activity shortly after sunset and
      continued biting at high levels throughout the night. Under unsprayed conditions,
      the use of exit and entrance interception traps demonstrated that doors, windows,
      and eaves were the primary mode of entry; whereas, cracks in the walls served a
      secondary role. The peak entrance time for An. vestitipennis occurred between
      6:45 P.M. and 9:45 P.M. and a peak exit time occurred between 11:45 P.M. and 4:45
      A.M. Additional trials were conducted after spraying one of the huts with DDT and
      another with deltamethrin. The excito-repellent properties of deltamethrin did
      not affect entrance times but did result in a peak exiting behavior that was five
      hours earlier than under pre-spray conditions. Deltamethrin also exhibited a
      repellency effect, showing 66% fewer An. vestitipennis entering the hut two weeks
      post-spray. DDT had an even more powerful repellency effect resulting in a 97%
      post-spray reduction of An. vestitipennis females entering the hut up to two
      weeks post-spray. The control hut showed only a 37% reduction in An.
      vestitipennis as compared to pre-spray conditions.

PMID- 10925799
TI  - Insecticide resistance status, esterase activity, and electromorphs from mosquito
      populations of Culex quinquefasciatus Say (Diptera: Culicidae), in Houston
      (Harris County), Texas.
AB  - Culex quinquefasciatus Say is a vector of St. Louis encephalitis (SLE) in Texas.
      This disease is endemic and prevalent in the Houston area. Disease prevention
      through mosquito control is mainly targeted against adults by application of a
      resmethrin-piperonyl butoxide formulation (Scourge). Immature mosquitoes were
      collected from eight areas in Harris County during 1998. The susceptibility
      status of these populations to Scourge, malathion, and resmethrin, the latter
      alone or with an esterase inhibitor as a synergist, was determined using a bottle
      assay with females. The population structure was investigated by electrophoretic
      analysis of esterases and their activity. Individual females were also analyzed
      for esterase activity by plate assay and for isoenzyme pattern by native PAGE.
      Bioassays indicated high levels of resistance to malathion in all areas. In
      addition, the effectiveness of Scourge in mosquitoes from area 51 deteriorated
      throughout the season. A localized, distinctive esterase pattern and activity
      level was observed in mosquitoes from different areas. Overall, the frequency of
      esterases Est alpha 2 (A2)/Est beta 2 (B2) was higher than that of Est beta 1
      (B1). Altogether, these results indicate the onset of a fragile situation for
      mosquito control that should be further analyzed to effectively maintain the SLE
      prevention program for Harris County.

PMID- 10925800
TI  - Isolations of enteric pathogens from synanthropic flies trapped in downtown Kuala
      Lumpur.
AB  - Four species of synanthropic flies were trapped in downtown Kuala Lumpur:
      Chrysomya megacephala, Chrysomya rufifacies, Musca domestica, and Musca sorbens.
      Burkholderia pseudomallei, the organism causing melioidosis, was the dominant
      bacteria isolated from Chrysomya megacephala. Klebsiella oxytoca, commonly
      associated with nosocomial infections, was commonly isolated from Chrysomya
      megacephala, Musca domestica, and Musca sorbens. Aeromonas hydrophila, the
      bacteria causing gastroenteritis, was predominantly isolated from Chrysomya
      megacephala and also from Musca domestica and Musca sorbens. A total of 18
      bacterial species was isolated from the synanthropic flies trapped. Burkholderia
      pseudomallei had been reported for the first time.

PMID- 10925801
TI  - Field evaluation of deltamethrin/S-bioallethrin/piperonyl butoxide and cyfluthrin
      against dengue vectors in Malaysia.
AB  - Deltacide (S-bioallethrin 0.71% w/v, deltamethrin 0.5% w/v, piperonyl butoxide
      8.9% w/v excipients to 100% w/v) and Solfac UL 015 (cyfluthrin 1.5% w/v) were
      evaluated against the sentinel sugar-fed adults and 4th-instar larvae of Aedes
      aegypti at 17 storey high-rise apartments in Malaysia using ULV applications. The
      impact of both insecticides on field populations of Ae. aegypti and Ae.
      albopictus larvae was monitored weekly using bottle containers. Both Deltacide
      and Solfac UL 015 showed adulticidal and larvicidal effects. This was the first
      field trial using Deltacide against dengue vectors in Malaysia and showed its
      potential for use in dengue vector control programs.

PMID- 10925802
TI  - The effects of flea egg consumption on larval cat flea (Siphonaptera: Pulicidae)
      development.
AB  - Cat flea larvae feeding on the feces of adult fleas that were maintained on cats
      and were provided with frozen flea eggs ad libitum each consumed an average of
      21.7 +/- 3.9 eggs and developed rapidly with 100% adult emergence. In contrast,
      93.4% of larvae held individually and provided with only flea feces did not
      survive to the adult stage. Developing larvae consumed eggs in the presence of
      yeast and rearing diet. In a second experiment, larvae provided with flea feces
      and eggs and maintained at 55% RH consumed 26.9 +/- 2.7 eggs per larva, compared
      to larvae maintained at 75% RH that consumed 20.4 +/- 1.9 eggs per larva.

PMID- 10925803
TI  - A state-by-state survey of ticks recorded from humans in the United States.
AB  - Based on tick specimens accessioned into the U.S. National Tick Collection, the
      species of ticks recorded as ectoparasites of humans are documented and compared
      for 49 U.S. states. A total of 44 tick species was recorded as parasites of
      humans, consisting of 11 species of soft ticks (Argasidae) and 33 species of hard
      ticks (Ixodidae). Four of the hard tick species are not native to the U.S. and
      were removed from travelers returning from foreign destinations. Therefore, we
      record 40 of the 84 species of U.S. ticks as ectoparasites of humans.
      Predictably, in the southern U.S. and Atlantic states, all active stages of the
      lone star tick, Amblyomma americanum (L.), were common ectoparasites of humans.
      Also, in the eastern U.S., adults of the American dog tick, Dermacentor
      variabilis (Say), and all active stages (especially adults) of the blacklegged
      tick, Ixodes scapularis (Say), were commonly recorded. In certain Rocky Mountain
      and western states, all active stages of the Rocky Mountain wood tick,
      Dermacentor andersoni (Stiles), predominated, whereas, in most far western
      states, adults of the western blacklegged tick, Ixodes pacificus Cooley and
      Kohls, were relatively common parasites of humans. Parasitism by Ornithodoros
      spp. soft ticks was mainly recorded in the western U.S. These findings, together
      with records of human parasitism by other tick species in the U.S., are briefly
      discussed with respect to tick-borne disease risk.

PMID- 10925804
TI  - Musca domestica as a mechanical carrier of bacteria in Chiang Mai, north
      Thailand.
AB  - The common house fly, Musca domestica L., was assessed for its potential as a
      mechanical carrier of bacteria in urban areas of Chiang Mai province, north
      Thailand. Sixty-one specimens (61.0%) were found to carry bacteria, with each
      harboring 1-5 bacteria. No significant difference between the sex of flies for
      carrying bacteria was found. A total of 21 bacteria was isolated, of which the
      most common was coagulase negative staphylococci (n = 38), followed by Viridans
      streptococci (n = 9). The highest bacterial load for all bacteria isolated was
      10(3)-10(4) (67%), followed by > 10(4) (26%) colonies per fly. It is recommended
      that fly control management measures, including sanitation improvement, should be
      implemented.

PMID- 10925806
TI  - Infection and seroconversion of cats exposed to cat fleas (Ctenocephalides felis
      Bouche) infected with Rickettsia felis.
AB  - Cats with no prior exposure to cat fleas were exposed to fleas infected with
      Rickettsia felis and monitored monthly for seroconversion via an indirect
      fluorescent assay (IFA). Each of 12 cats continually infested with fleas,
      seroconverted by four months post-exposure. Three of six cats fed on by 50 fleas
      for 15 minutes once per week also seroconverted by month four. Rickettsia felis
      DNA was detected by PCR in the blood of five of the 16 cats.

PMID- 10925805
TI  - Autogeny in Culex pipiens quinquefasciatus say.
AB  - Autogeny was observed in a laboratory colony of Culex pipiens quinquefasciatus
      Say originating from Hyderabad, India. In a strain selected for an autogeny for
      15 generations, all females, both mated and unmated, were able to mature eggs
      although the unmated females were unable to oviposit them. Ingesting glucose had
      little effect on the expression of autogeny and on the number of eggs in rafts in
      the laboratory experiments. Most autogenous females can ingest blood during first
      gonotrophic cycle, if the host is available. The blood feeding that occurred
      during the first cycle to initiate the second cycle was not confirmed, however,
      we cannot exclude this possibility.

PMID- 10925807
TI  - "Time given freely to worthwhile causes:" Anna S. Espenschade's contributions to
      physical education.

PMID- 10925808
TI  - Understanding physical activity intention in Canadian school children and youth:
      an application of the theory of planned behavior.
AB  - The purpose of this study was to investigate the efficacy of the theory of
      planned behavior in predicting physical activity intention in a nationwide sample
      of Canadian children and youth. The study sample consisted of participants from
      Grades 3, 5, 8, and 11 from schools across Canada. School participation was
      determined by means of a randomly stratified sample design. Results show that the
      direct measures of the theory of planned behavior explained 47% of the
      variability in the measure of physical activity intention. In addition, notable
      differences in the relative contributions of the predictor variables of attitude,
      subjective norm, and perceived behavioral control were found across grade and
      grade-by-gender subgroups. The present study provides evidence that in a
      population of children and youth the determinants display a pattern of change
      developmentally.

PMID- 10925809
TI  - Validation of criterion-referenced standards for the mile run and progressive
      aerobic cardiovascular endurance tests.
AB  - The purpose of this study was to validate criterion-referenced standards for
      cardiovascular endurance tests using the criterion-groups validation model.
      Adolescent boys and girls assigned to either untrained or trained groups were
      administered the mile run and Progressive Aerobic Cardiovascular Endurance Run
      (PACER) tests. Selection of optimal criterion standards was based on finding a
      cutting score that minimized the probability of misclassification errors and
      maximized the probability of making correct decisions based on participation in
      physical activity. The results of this study suggest that recent changes in
      FITNESSGRAM standards are appropriate, especially for the PACER test. While
      modifications of standards have corrected somewhat for disparities in passing
      rates between the mile run and the PACER, especially for girls, further study of
      standards is necessary.

PMID- 10925810
TI  - Learning and remembering strategies of novice and advanced jazz dancers for skill
      level appropriate dance routines.
AB  - This study examined the influence of the challenge level of to-be-learned
      stimulus on learning strategies in novice and advanced dancers. In Study 1, skill
      level appropriate dance routines were developed for novice and advanced jazz
      dancers. In Study 2, 8 novice and 9 advanced female jazz dancers attempted to
      learn and remember the two routines in mixed model factorial design, with one
      between-participants factor: skill level (novice or advanced) and two within
      participants factors: routine (easy or difficult) and performance (immediate or
      delayed). Participants were interviewed regarding the strategies used to learn
      and remember the routines. Results indicated that advanced performers used
      atypical learning strategies for insufficiently challenging stimuli, which may
      reflect characteristics of the stimuli rather than the performer. The qualitative
      data indicate a clear preference of novice and advanced performers for spatial
      compatibility of stimuli and response.

PMID- 10925811
TI  - A review of the literature on the application of blood ammonia measurement in
      sports science.
AB  - This article summarizes previous studies on blood ammonia levels in relation to
      exercise. The dynamics of blood ammonia were reviewed with consideration to its
      production, removal, and distribution in various tissue compartments. During
      intense exercise, the primary source of ammonia is adenosine monophosphate
      deamination. Catabolism of branched-chain amino acids becomes important during
      submaximal exercise. Ammonia response to various types of exercise was also
      compared to lactate response. A comprehensive summary on factors affecting blood
      ammonia levels is provided. These reveal the possibility of applying blood
      ammonia measurement in monitoring and prescribing exercise, indirect measurement
      of muscle fiber composition, and muscle glycogen levels. However, more studies
      need to be conducted to evaluate these possibilities before blood ammonia
      measurement can be widely used.

PMID- 10925812
TI  - Physical fitness of adults with an intellectual disability: a 13-year follow-up
      study.
AB  - The purpose of this study was to describe the change in physical fitness of
      middle-aged adults with an intellectual disability over a period of 13 years.
      Participants were 32 adults who worked in a supported work environment in
      Montreal and had been participants in a physical fitness study in 1983. Using the
      Canadian Standardized Test of Fitness, the participants were evaluated for
      cardiovascular endurance, muscular strength, muscular endurance, flexibility, and
      body composition. A home visit prior to the testing session refamiliarized the
      participants with the test procedures. Two forms of analysis were used to
      describe the change in fitness over 13 years. First, a 2 x 2 (Group x Time)
      analysis of variance for each dependent variable assessed change over time.
      Second, effect sizes were calculated to measure the magnitude of change in
      fitness over the 13-year period in comparison to those without an intellectual
      disability. As expected, the physical fitness levels of the participants were low
      when compared to those without a disability and declined over the 13 years. In
      addition, the magnitude of change over the 13 years, as compared to those without
      a disability, was greater for male and female participants for body mass index
      and percentage of body fat and for female participants for cardiovascular
      endurance and sit-ups. It appears that adults with an intellectual disability may
      be particularly at risk for declining health associated with aging and low
      physical fitness.

PMID- 10925813
TI  - The effect of a psyching strategy on neuromuscular activation and force
      production in strength-trained men.
AB  - Force and electromyographic (EMG) activity of the biceps and triceps brachii were
      measured in 15 strength-trained men during maximal isometric action of the
      forearm flexors, with the elbow at 90 degrees, following 20-s periods of psyching
      (PSY), reading aloud (RA), and mental arithmetic (MA). Perceived arousal and
      attentional focus ratings for PSY were greater than those obtained for RA and MA,
      which were undifferentiated. Perceived effort, biceps and triceps EMG, and
      maximal force did not differ across conditions. Therefore, in highly trained men
      under conditions of brief exertion, when the biomechanics of the muscular action
      were controlled, psyching resulted in a perception of enhanced readiness but did
      not influence force or muscular activation differently from psychological states
      that were preceded by distraction.

PMID- 10925814
TI  - Testing relationships from the hierarchical model of intrinsic and extrinsic
      motivation using flow as a motivational consequence.
AB  - The purpose of this study was to test a motivational model based on Vallerand's
      (1997) Hierarchical Model of Intrinsic and Extrinsic Motivation. This model
      incorporates situational and contextual motivational variables, and was tested
      using a time-lagged design. Master's level swimmers (N = 104) completed a
      questionnaire on two separate occasions. At Time 1, situational social factors
      (perceptions of success and perceptions of the motivational climate), situational
      motivational mediators (perceptions of autonomy, competence, and relatedness),
      situational motivation, and flow were assessed immediately following a swim
      practice. Contextual measures of these same variables were assessed at Time 2, 1
      week later, with the exception of flow. Results of a path analysis supported
      numerous links in the hypothesized model. Findings are discussed in light of
      research and theory on motivation and flow.

PMID- 10925815
TI  - Influence of arm position and lung volume on the center of buoyancy of
      competitive swimmers.

PMID- 10925816
TI  - Which should it be called: convergent validity or discriminant validity?

PMID- 10925817
TI  - Adaptation in the timing of catching under changing environmental constraints.

PMID- 10925818
TI  - Male and female differences and the specificity of fatigue on skill acquisition
      and transfer performance.

PMID- 10925819
TI  - Assessment of physical activity by self-report: status, limitations, and future
      directions.

PMID- 10925820
TI  - Reliability, validity, and methodological response to the assessment of physical
      activity via self-report.

PMID- 10925821
TI  - Objective monitoring of physical activity using motion sensors and heart rate.
AB  - Although neither motion sensors nor heart rate are perfect markers of physical
      activity, they certainly eliminate subjectivity of obtaining physical activity
      information. The objective method of choice depends on how the measurement will
      be used. For example, if walking behavior is the desired outcome, then a
      pedometer may be sufficient. If patterns and intensity of activity over longer
      periods of times such as a week or longer are needed, then an accelerometer with
      large memory capacity should be selected. In the future, efforts should be
      directed towards developing an objective motion sensor as inexpensive as a
      pedometer but with the data acquisition capabilities of the CSA or Tritrac
      accelerometer. Providing simultaneous heart rate with motion is also recommended
      to further verify that elevated heart rate does in fact represent a physical
      activity response. As the cost of the electronic components continues to
      decrease, these activity monitor configurations may become possible.

PMID- 10925822
TI  - Validity and reliability issues in objective monitoring of physical activity.
AB  - Major technical advances have occurred within the last 10 years in the field of
      physical activity monitoring. The biggest one is real-time data acquisition, and
      the development of computer microchips that allow vast amounts of information to
      be stored and later recalled. It is evident that no single motion sensor will
      provide an accurate estimate of energy expenditure across all activities. Future
      directions for research include the use of combined instruments such as an
      accelerometer plus questionnaire, multiple motion sensors, or dual HR-motion
      sensor technology.

PMID- 10925823
TI  - Issues in the assessment of physical activity in women.

PMID- 10925824
TI  - Comment on issues in the assessment of physical activity in women.

PMID- 10925825
TI  - Ethnic and cultural issues in assessing physical activity.
AB  - Although the physical activity questionnaire, in general, is the most common
      measure of physical activity levels in minority subgroups, additional measures
      may be needed to supplement the information collected by questionnaire alone. The
      most frequent types of physical activities performed in many of these minority
      groups are often lower intensity activities. However, when assessing activity by
      questionnaire, we know that lower intensity activities like walking and housework
      tend to be less reproducible than higher intensity activities such as many of the
      organized sports (Kriska et al., 1990; Sallis et al., 1985). Therefore, the
      activity questionnaire alone may not be the best way to quantify these lower
      intensity, variable frequency, life-style activities. As Figure 3 reminds us,
      measurement of lower intensity activities may require the use of more objective
      measures. One feasible approach may be to use a simple, inexpensive, objective
      measure of activity like an activity monitor or a pedometer. Step monitors are
      now successfully being used to estimate levels of movement expressed as "daily
      steps taken throughout the day" and to document activity changes in intervention
      efforts. However, activity monitors also have their own set of limitations such
      as the inability of capturing cycling, swimming, and upper body movement.
      Likewise, monitors certainly are not as practical as physical activity
      questionnaires in assessing activity in population studies. It is likely that a
      combination of the two methods of activity assessment would work best.
      Individuals who have scored low on the activity questionnaire could be given a
      step monitor to further evaluate their physical activity levels. Although
      promising, much more work needs to be done in this area.

PMID- 10925826
TI  - Reliability, validity, and methodological issues in assessing physical activity
      in a cross-cultural setting.
AB  - In summary, to complement the issues raised in Dr. Kriska's paper, this paper
      identified a number of methodological issues that researchers need to address
      before valid cross-cultural comparisons can be performed (see summary of issues
      and proposed actions for researchers in Table 1). In addition, this paper
      cautions us to interpret published findings in light of the methodological issues
      that were raised in this paper. This paper selectively addressed some
      methodological issues and leaves ample room for other researchers to think of
      other important issues. Many of the issues raised in this paper are related to
      the use of questionnaires to make cross-cultural comparisons. However, many of
      the methodological issues presented in this paper apply to other methods of
      assessing physical activity behaviors. As a final remark, I do want to
      acknowledge that other methods used to measure physical activity (including
      activity monitor) provide valuable but different information than questionnaires.
      It remains that in large-scale epidemiological studies, questionnaires are often
      the most practical instrument to use, and given the errors associated with
      questionnaires, we need to consider whether questionnaires are better at
      measuring physical activity behaviors at the group level or individual level.

PMID- 10925827
TI  - Measurement issues in the assessment of physical activity in children.
AB  - This paper reviewed the nature of children's physical activity patterns and how
      the unique nature of children can impact the assessment of physical activity. To
      accurately assess children's activity patterns, an instrument must be sensitive
      enough to detect, code, or record sporadic and intermittent activity. Care also
      must be used to select criterion measures that reflect appropriate physical
      activity guidelines for children. A number of different measurement approaches
      have been described for assessing children's activity, but no specific method can
      be identified as the best option for all studies. Selection of an appropriate
      instrument depends on the specific research question being addressed as well as
      the relative importance of accuracy and practicality (Baranowski & Simons-Morton,
      1991). For example, accurate measures of energy expenditure using doubly-labeled
      water, indirect calorimetry, or heart rate calibration equations may be needed
      for certain clinical studies, but the cost and inconvenience would make them
      impractical for field-based assessments on larger samples. The "accuracy
      practicality" trade-off presents a more challenging predicament with children
      than for adults. In adults, a number of self-report instruments have been found
      useful for large epidemiological studies or interventions where less precision is
      needed. Because of developmental differences, especially in ability to think
      abstractly and perform detailed recall (Going et al., 1999; Sallis, 1991),
      children are less likely to make accurate self-report assessment than adults.
      Though self-report methods are still likely to be a principal source of
      information for many studies, other approaches (or the use of combined measures)
      may be needed to better characterize children's activity levels. While objective
      instruments (e.g., direct observation or activity monitoring) require more time
      and resources than self-report, there are options available to simplify data
      collection. One approach may be to focus assessments on key times or places that
      allow children to be active. The time after school, for example, appears to be a
      critical period that defines their propensity for physical activity (Hager,
      1999). Monitoring of entire groups for discrete periods of time (e.g., recess or
      physical education) may also be useful to understand variability in activity
      patterns since children would all be exposed to the same stimulus or opportunity
      to be active. Proxy measures may also be useful in studying activity in children.
      For example, several studies (Baranowski, Thompson, DuRant, Baranowski, & Puhl,
      1993; Sallis et al., 1993) have demonstrated that time spent outside is strongly
      predictive of activity in children. Involvement in community sports programs may
      also be a useful proxy measure as sports programs have been found to account for
      approximately 55-65% of children's moderate to vigorous activity (Katzmarzyk &
      Malina, 1999). Another option for improving assessments in children is to employ
      multiple measures of physical activity. A number of studies (Coleman, Saelens,
      Wiedrich-Smith, Finn, & Epstein, 1997; McMurray et al., 1998; Sallis et al.,
      1998; Simons-Morton et al., 1994) have reported differences in levels of activity
      when activity monitors were compared with self-report data. The method of
      measurement has also been shown to influence the results of studies on the
      determinants of physical activity in children (Epstein, Paluch, Coleman, Vito, &
      Anderson, 1996). While we do not currently know which measure is most accurate,
      reporting the results with different instruments provides a more complete
      description of children's activity and permit a triangulation of outcomes. In
      summary, there remains no single way of obtaining a highly accurate account of
      physical activity or energy expenditure in children. The nature of children's
      movement patterns, the various types of activities engaged in, and the inherent
      limitations of each assessment tool limit the ultima

PMID- 10925828
TI  - How many days was that? Intra-individual variability and physical activity
      assessment.

PMID- 10925829
TI  - Assessment of physical activity in older adults.

PMID- 10925830
TI  - Reliability, validity, and methodological issues in assessing physical activity
      in older adults.

PMID- 10925831
TI  - Public health surveillance of physical activity.
AB  - There is a clear public health need to measure and track physical activity
      behavior. Surveillance systems should be flexible enough to keep up with
      scientific advances in identifying dose-response relationships and in developing
      new assessment techniques, and new ways to assess community indicators associated
      with physical activity. Having a strong public health surveillance system that
      produces data that can be used to plan, guide, and evaluate programs is essential
      for increasing the prevalence of an important health-related behavior: physical
      activity.

PMID- 10925832
TI  - Reliability and validity issues concerning large-scale surveillance of physical
      activity.
AB  - The BRFSS is our major source of population-based information on physical
      activity in the United States. The top priority for the immediate future should
      be to make sure that the information obtained from the BRFSS in its current form
      is both reliable and valid. As outlined in this report, this task could be
      completed in relatively short time frame and at reasonable cost in terms of both
      financial and human resources. The development of an additional module to assess
      light-to-moderate activity and strength is currently underway with support from
      the CDC. As suggested in this report, this task may prove to be extremely
      difficult, or it may be difficult to develop an instrument of this type given the
      constraints of a population based telephone survey. The current focus on the
      health benefits of moderate activity and the interest in tracking this type of
      activity behavior on a population basis as it relates to national physical
      activity objectives both argue in favor of developing a physical activity
      assessment instrument that provides a valid and reliable measurement of moderate
      activity. Given the complexity and uncertainty of this task it is important to
      develop a procedure that will allow for periodic evaluation of progress and the
      potential for success to minimize the risk of making a considerable financial
      investment in an instrument that may be of limited utility.

PMID- 10925833
TI  - Assessment of physical activity: an international perspective.

PMID- 10925834
TI  - Score equivalence is at the heart of international measures of physical activity.

PMID- 10925835
TI  - New approaches to determining reliability and validity.

PMID- 10925836
TI  - Future possibilities in electronic monitoring of physical activity.

PMID- 10925837
TI  - Measuring the determinants of physical activity in the community: current and
      future directions.

PMID- 10925838
TI  - 1,3-butadiene: cancer, mutations, and adducts. Part I: Carcinogenicity of 1,2,3,4
      diepoxybutane.
AB  - Reports in the literature suggest that one reason for the greater sensitivity of
      mice to the carcinogenicity of 1,3-butadiene (BD) is that exposed mice metabolize
      much more of the BD to 1,2,3,4-diepoxybutane (BDO2) than do exposed rats. The
      purpose of this study was to determine the tumorigenicity of BDO2 in rats and in
      mice exposed to the same concentration of the agent. Female B6C3F1 mice and
      Sprague-Dawley rats, 10 to 11 weeks old, 56 per group, were exposed by inhalation
      to 0, 2.5, or 5.0 ppm BDO2, 6 hours/day, 5 days/week for 6 weeks. Preliminary
      dosimetry studies in rodents exposed for 6 hours to 12 ppm BDO2 indicated that
      blood levels would be expected to be approximately 100 and 200 pmol/g at the two
      exposure concentrations in the rat and twice those levels in the mouse. During
      the 6-week exposure, the mice at the high exposure level showed signs of labored
      breathing during the last week, and four mice died. In the others, however, the
      respiratory symptoms disappeared after exposure ended. Rats showed no clinical
      signs of toxicity during exposure but developed labored breathing after the end
      of the exposure leading to the death of 13 rats within 3 months. At the end of
      the exposure, some animals (8 per group) were evaluated for the acute toxicity
      resulting from the BDO2 exposure. The remaining exposed rats and mice were held
      for 18 months for observation of tumor development. At the end of the exposure,
      rats had no biologically significant alteration in standard hematological
      parameters, but mice had a dose-dependent increase in neutrophils and decrease in
      lymphocytes. In both species the significant histopathologic lesions were in the
      nose, concentrated around the main airflow pathway. Necrosis, inflammation, and
      squamous metaplasia of the nasal mucosa, as well as atrophy of the turbinates,
      were all present at the end of exposure to 5.0 ppm. Within 6 months, necrosis and
      inflammation subsided, but squamous metaplasia remained in the mice. In rats that
      died after exposure, squamous metaplasia was seen in areas of earlier
      inflammation and, in other rats, extended beyond those areas with time. The
      metaplasia was severe enough to restrict and occlude the nasopharyngeal duct.
      Later, keratinizing squamous cell carcinomas developed from the metaplastic foci
      in rats but not mice. At the end of 18 months, the only significant increase in
      neoplasia in the exposed rats was a dose-dependent increase in neoplasms of the
      nasal mucosa (0/47, 12/48, and 21/48 for the control, 2.5 ppm, and 5.0 ppm
      exposures, respectively). Neoplasia of the nasal mucosa did not increase
      significantly in the mice; neoplastic lesions in the mice were observed in
      reproductive organs, lymph nodes, bone, liver, Harderian gland, pancreas, and
      lung. The only significant increase in neoplasms in a single organ in the mice
      was in the Harderian gland (0/40, 2/42, and 5/36 for the control, 2.5 ppm, and
      5.0 ppm exposures, respectively). This tumor accounts for the apparent trend
      toward an increase in total neoplastic lesions in mice as a function of dose
      (10/40, 7/42, and 16/36 for control, 2.5 ppm, and 5.0 ppm exposures,
      respectively). These findings indicate that the metabolite of BD, BDO2, is
      carcinogenic in the respiratory tract of rats. An increase in respiratory tract
      tumors was not observed in similarly exposed mice despite the fact that
      preliminary studies indicated mice should have received twice the dose to tissue
      compared with the rats. High cytosolic activity of detoxication enzymes in the
      mouse may account, in part, for the differences in response.

PMID- 10925840
TI  - 1,3-butadiene: cancer, mutations, and adducts. Part III: In vivo mutation of the
      endogenous hprt genes of mice and rats by 1,3-butadiene and its metabolites.
AB  - 1,3-Butadiene (BD), an important chemical used mainly in the production of
      synthetic rubber, is a potent carcinogen in mice, a weak carcinogen in rats, and
      a suspected carcinogen in humans. To provide a better understanding of the
      mutagenic mechanisms involved in interspecies differences in BD-induced
      carcinogenesis, studies were conducted in rodents to test two hypotheses: (a) the
      mutagenic potency of BD at the hypoxanthine-guanine phosphoribosyltransferase
      (hprt) locus of T lymphocytes (T cells) can be used to quantify interspecies
      differences in BD-induced carcinogenicity in exposed rodents and (b) comparison
      of the mutagenic potency and specificity of BD and racemic mixtures of two epoxy
      metabolites, 1,2-epoxy-3-butene (BDO) and 1,2,3,4-diepoxybutane (BDO2), at the
      hprt locus of T cells can be used to define the relative contribution of each
      intermediate to observed BD mutagenicity in each species. The first hypothesis
      was investigated by determining the effects of exposure duration and elapsed time
      after exposures on hprt mutant frequencies (MFs) in T cells from thymus and
      spleen of female B6C3F1 mice and F344 rats (4 to 5 weeks old). In this study,
      rodents were exposed by inhalation to 0 or 1,250 parts per million (ppm) BD for
      up to 2 weeks, or to 0 or 625 ppm BD for up to 4 weeks (with all exposures 6
      hours/day, 5 days/week). The second hypothesis was examined by defining the
      effects of exposure concentration and elapsed time after exposures on the hprt
      MFs in splenic T cells from mice and rats exposed by inhalation to BD (0, 20,
      62.5, or 625 ppm), BDO (0, 2.5, or 25 ppm), or BDO2 (0, 2, or 4 ppm) for 4 weeks
      (all exposures 6 hours/day, 5 days/week). The hprt MFs were measured weekly or
      biweekly using the T cell cloning assay for up to 10 weeks after the last
      exposure. The mutagenic potency of BD (represented by the difference in the areas
      under the mutant T cell "manifestation" curves [or the "change in MFs over time"]
      of exposed versus control animals) was significantly greater in mice (4.4-fold)
      than in rats following 2 weeks of exposure to 1,250 ppm BD. Mutagenic potency in
      mice was 8.5-fold greater than that in rats following 4 weeks of exposure to 625
      ppm BD. These hprt MF data provide the first evidence that BD is mutagenic in the
      rat, albeit the mutagenic response was significantly less than that observed in
      similarly exposed mice. In addition, the MF data from the two exposure-duration
      studies indicate that both exposure concentration and exposure duration are
      important in determining the magnitude of the mutagenic response to BD. The
      relative contribution of BDO versus BDO2 to overall BD mutagenicity was evaluated
      by exposing mice and rats to carefully chosen concentrations of BD and racemic
      mixtures of BDO and BDO2 (that is, 62.5, 2.5, and 4.0 ppm, respectively) and
      comparing the mutagenic potency of each compound when comparable blood levels of
      metabolites were achieved. The resulting MF data indicate that (+/-)-BDO2 is a
      major contributor to the mutagenicity of BD in mice at lower BD exposure levels
      (< or = 62.5 ppm), whereas other metabolites and stereochemical configurations
      are responsible for mutations in BD-exposed rats and for the incremental
      mutagenic effects at higher exposure levels in mice. Molecular analysis of hprt
      cDNA from expanded T cell clones from control and BD-exposed mice demonstrated an
      increased frequency of large deletions in exposed animals (p = 0.016), presumably
      associated with in situ formation of (+/-)-BDO2, meso-BDO2, or both. Results of
      these mutagenicity experiments, along with data from collaborative studies of DNA
      adducts from the same animals, should provide a better understanding of the
      interspecies variation in carcinogenic response to BD and improve the
      extrapolation of rodent data to the estimation of cancer risk in exposed persons.

PMID- 10925839
TI  - 1,3-butadiene: cancer, mutations, and adducts. Part II: Roles of two metabolites
      of 1,3-butadiene in mediating its in vivo genotoxicity.
AB  - 1,3-Butadiene (BD) is carcinogenic in mice and rats, with mice being more
      susceptible than rats to its carcinogenic effects. 1,3-Butadiene is mutagenic in
      the bone marrow and spleen cells of B6C3F1 lacI transgenic mice. The goal of this
      research was to assess the roles of two BD metabolites, 1,2-epoxy-3-butene (BDO)
      and 1,2,3,4-diepoxybutane (BDO2), in the mutagenicity and mutational spectrum of
      the parent compound BD by determining the mutagenicity and mutational spectra of
      BDO and BDO2 in human and rodent cells in vitro and in vivo. In human TK6
      lymphoblastoid cells (TK6 cells), BDO exposure increased the frequency of G.C-
      >A.T transitions and A.T-->T.A transversions (Fisher exact test; p < 0.05). The
      most striking difference in the type of base-substitution mutations between BDO
      exposed and BDO-unexposed TK6 cells was the 19-fold increase in A.T-->T.A
      transversions. 1,2,3,4-Diepoxybutane increased the frequency of A.T-->T.A
      transversions (Fisher exact test; p < 0.05) and the frequency of deletions in
      exposed TK6 cells compared with unexposed controls. Exposure of Rat2 lacI
      transgenic fibroblasts (Rat2 cells) to BDO increased the frequency of three types
      of base-substitution mutations: G.C-->A.T transitions, G.C-->T.A transversions,
      and A.T-->T.A transversions. Exposure of Rat2 cells to BDO2-induced dose
      dependent increases in micronuclei at exposure levels that apparently did not
      induce mutagenicity at the lacI transgene. The lack of detectable mutagenicity at
      the lacI transgene in Rat2 cells exposed to BDO2 probably reflects the poor
      recovery of large deletions by this lambda phage-based mutagenicity assay.
      Inhalation exposure of B6C3F1 lacI transgenic mice (lacI mice) and F344 lacI
      transgenic rats (lacI rats) to BDO (29.9 parts per million [ppm]; 6 hours/day; 5
      days/week for 2 weeks) did not increase the lacI mutant frequency (MF) in bone
      marrow or spleen cells of mice and rats, but in the cells of mouse lung (a tumor
      target organ for BD), significant mutagenicity was observed. An increased lacI MF
      was also observed in the bone marrow cells of rats exposed to BDO. Inhalation
      exposure of lacI mice and lacI rats to BDO2 (3.8 ppm; 6 hours/day; 5 days/week
      for 2 weeks) did not increase the lacI MF in bone marrow or spleen cells of mice
      or in the spleen cells of rats. An increased lacI MF was observed in the bone
      marrow cells of rats exposed to BDO2. In the present study, BDO specifically
      induced G.C-->A.T and A.T-->T.A transversions in vitro at both the endogenous
      hypoxanthine phosphoribosyltransferase (hprt) gene and the lacI transgene in Rat2
      cells. It also induced an increased frequency of G.C-->T.A transversions in Rat2
      cells. These types of mutations also occur at an increased frequency in mice
      exposed to the parent compound, BD. This finding demonstrates the induction of
      consistent mutational types across biological systems by BDO and indicates that
      BDO, but not BDO2, probably has a role in mediating the mutations recovered at
      the lacI transgene in animals exposed to the parent compound, BD. Therefore, it
      is apparent that in mice exposed to BD at carcinogenic levels, BDO and BDO2 act
      in concert to mediate the range of genotoxic responses. These data demonstrate
      that certain DNA adducts (guanine or adenine) may be useful biomarkers for BD
      genetic effects. However, other DNA lesions that can account for BDO2-induced
      deletions and chromosomal alterations also need to be considered as biomarkers
      for BD-induced genotoxicity.

PMID- 10925841
TI  - 1,3-butadiene: cancer, mutations, and adducts. Part IV: Molecular dosimetry of
      1,3-butadiene.
AB  - Analysis of N7-guanine adducts derived from 1,3-butadiene (BD) was conducted with
      use of liquid chromatography-mass spectrometry (LC-MS) in combination with stable
      isotope methods. The N7-guanine adducts were shown to undergo spontaneous
      depurination from DNA in vitro in both calf-thymus DNA and TK6-cell DNA. A
      comparison was made between BD-derived N7-guanine adduct concentrations both in
      liver DNA and urine of rats and mice exposed to BD. This has provided insight
      into the exposure of the animals to 1,2-epoxy-3-butene (BDO), 1,2,3,4
      diepoxybutane (BDO2), and 1,2-dihydroxy-3,4-epoxybutane (BDO-diol), the three
      oxidative metabolites of BD thought to be responsible for BD-mediated
      carcinogenesis. The liver DNA of mice contained more of the two N7-guanine
      adducts of BDO--N7-2-hydroxy-3-butenyl-1-guanine (2HB1G) and N7-1-hydroxy-3
      butenyl-2-guanine (1HB2G)--than the amounts in rats during the 10-day BD exposure
      and the 6 days after exposure that were monitored. An excess of 1HB2G over 2HB1G
      by a factor of approximately 10 in the rat liver and a factor of approximately 5
      in the mouse liver was also observed. This regioselective difference was apparent
      during both the 10-day exposure and the 6 days after exposure. The half-lives of
      2HB1G and 1HB2G were estimated as 4.3 days and 3.5 days, respectively, in the DNA
      of BD-exposed mice and rats. Higher amounts of 2HB1G and 1HB2G appeared in rat
      urine compared with mouse urine after the 10-day exposure to 1,250 ppm BD.
      Analysis of liver DNA for N7-guanine adducts derived from BDO2 revealed the
      presence of two diastereomeric forms of N7-(2,3,4-trihydroxybutyl)-1-guanine
      (THBG). One of the diastereomers [(+/-)-THBG] was formed by reaction of DNA with
      (+/-)-BDO2 or BDO-diol, and the other diastereomer (meso-THBG) was formed by
      reaction of DNA with meso-BDO2 or BDO-diol. There was more (+/-)-THBG and meso
      THBG in liver DNA of mice compared with amounts in rats during the 10 days of BD
      exposure and the 6 days after exposure. A twofold excess of (+/-)-THBG over meso
      THBG in rat liver was found at all of the time points monitored. After 10 days of
      exposure to BD, (+/-)-THBG in mouse liver was also present in an almost twofold
      excess over meso-THBG. At 6 days after exposure to BD, however, (+/-)-THBG and
      meso-THBG were present in almost equal amounts in mouse liver. Furthermore,
      amounts of the two THBG diastereomers in mouse liver 6 days after exposure to BD
      were almost fivefold greater than amounts in rat liver. The half-lives of (+/-)
      THBG and meso-THBG appeared to be longer in mouse liver (4.1 days and 5.5 days,
      respectively) than in rat liver (3.6 days and 4.0 days, respectively). Higher
      amounts of (+/-)-THBG were excreted in rat urine compared with mouse urine. It is
      noteworthy that each of the N7-guanine adducts derived from BD was present in
      higher concentrations in the liver DNA of mice exposed to 1,250 ppm BD than in
      the liver DNA of rats exposed to the same dose. Conversely, each of the adducts
      was present in higher concentrations in the urine of rats compared with the urine
      of mice after exposure to 1,250 ppm BD.

PMID- 10925842
TI  - 1,3-butadiene: cancer, mutations, and adducts. Part V: Hemoglobin adducts as
      biomarkers of 1,3-butadiene exposure and metabolism.
AB  - 1,3-Butadiene (BD) is an important chemical used largely in the manufacture of
      synthetic rubber and thermoplastic resins. In addition, it has been identified in
      cigarette smoke, automobile exhaust, and gasoline vapor. The objective of this
      research was to develop highly sensitive and specific assays for the detection
      and quantitation of hemoglobin adducts of three BD metabolites: 1,2-epoxy-3
      butene (BDO), 1,2,3,4-diepoxybutane (BDO2), and 1,2-dihydroxy-3,4-epoxybutane
      (BDO-diol). We have successfully developed an assay for both N-(2-hydroxy-3
      butenyl)valine (HBVal) and N-(2,3,4-trihydroxybutyl)valine (THBVal) in
      hemoglobin. The six adducts measured were the two diastereomers (isomers I and
      II) of HBVal and the four diastereomers of THBVal (isomers I through IV, which
      were eluted as three peaks, 1, 2, and 3). HBVal and THBVal were measured in
      control and exposed B6C3F1 mice and Sprague-Dawley rats (1,000 ppm BD for 13
      weeks at 6 hours/day, 5 days/week). In a second set of animal exposures, total
      THBVal was determined in B6C3F1 female mice (n = 5) exposed to 1,250 ppm BD for
      1, 5, or 10 days (6 hours/day, 5 days/week). THBVal adducts were also monitored
      in occupationally exposed Chinese workers and nonoccupationally exposed U.S.
      laboratory workers. This study utilized the modified Edman degradation method of
      Tornqvist and colleagues (1986). Briefly, the samples were subjected to Edman
      degradation, Centricon-30 ultrafiltration, washing on C18 columns, and
      acetylation for isomers of THBVal only, followed by gas chromatography-mass
      spectrometry (GC-MS) quantitation. For the HBVal assay, an authentic internal
      standard globin alkylated with [2H6]BDO was used; for the THBVal assay, a
      synthesized external standard, THB[13C5]Val, was used after Edman degradation.
      The mean +/- SD amounts of total HBVal measured in exposed mice (in pmol/g
      globin) were 16,560 +/- 3,910 for female mice (n = 4) and 12,400 +/- 2,030 for
      male mice (n = 5). The corresponding values for rats were 8,690 +/- 930 for
      female rats (n = 5) and 5,480 +/- 2,880 for male rats (n = 3). The total amount
      of THBVal (eluted peaks 1, 2, and 3) in male mice (n = 5) was 78,900 +/- 13,700;
      and in females (n = 2) was 56,100 +/- 100. In male rats (n = 3), the detected
      value was 9,650 +/- 1,620 and in females (n = 3) the value was 21,600 +/- 6,780.
      In control male mice (n = 4), the total level of THBVal isomers was approximately
      27 pmol/g globin. In a control male rat, total THBVal was approximately 15 pmol/g
      globin. In the time course study, the amount of THBVal adducts increased linearly
      with exposure, resulting in values of 4,200 +/- 830, 19,760 +/- 1,780, and 35,940
      +/- 3,460 pmol/g globin following 1, 5, or 10 days of exposure to 1,250 ppm BD,
      respectively. Detection of HBVal in human samples was difficult due to low
      concentrations of adducts and a high background in the chromatograms. In a pooled
      sample from 4 individuals, we performed multiple separations with high-pressure
      liquid chromatography (HPLC) of the derivatized adducts and detected 4.6 pmol/g
      globin (that is, 2.7 and 1.9 pmol/g globin for isomers I and II, respectively).
      We measured the amounts of THBVal in both nonoccupationally exposed U.S.
      laboratory workers and occupationally exposed workers from a polybutadiene plant
      in China. The mean total amount of THBVal among the U.S. laboratory workers was
      36 +/- 23 pmol/g globin for nonsmokers (n = 7) and 40 +/- 9 for smokers (n = 4),
      compared with a mean total amount of 39 +/- 13 pmol/g globin in a control set of
      Chinese workers (n = 25). These control values are overestimations of the true
      values because the amounts of THBVal in globin samples from other unexposed
      individuals (15 of 51) were below our limit of detection. BD-exposed Chinese
      workers had a total amount of 88 +/- 59 pmol/g globin THBVal. The difference
      between smokers and nonsmokers was not significant, whereas the difference
      between control and exposed Chinese workers was highly significant (p < 0.001).

PMID- 10925843
TI  - [Insulin-like growth factor II (IGF-II)--regulator peptide from the insulin
      superfamily].

PMID- 10925844
TI  - [Comparative study of effect of free and chelated cadmium cation on the activity
      of glutathione-S-transferase, growth, and endocytosis in infusoria Tetrahymena
      pyriformis culture].

PMID- 10925845
TI  - [Lipid peroxidation in embryos and larva of sea urchin Strongylocentrotus
      intermedius].

PMID- 10925846
TI  - [The role of cysteine sulfhydryl groups in activation of the adenylate cyclase
      signal system by biogenic amines in mollusk and rat tissues].

PMID- 10925848
TI  - [Glucose-6-phosphate dehydrogenase activity in erythrocytes from the Black sea
      fishes].

PMID- 10925847
TI  - [Kinetic analysis of the 'substrate protective effect' for cholinesterases of
      various origin].

PMID- 10925849
TI  - [Na, K-Pump activation by isoproterenol, methylxanthines, and iodoacetate in
      erythrocytes of the frog Rana temporaria].

PMID- 10925850
TI  - [Effect of arginine vasotocin on water and ion release by the kidney in the
      lamprey Lampetra fluviatilis].

PMID- 10925851
TI  - [Effect of uni- and bilateral lesions in the caudate nucleus by kainic acid on
      the electroencephalogram in the cycle wakefulness-sleep in Wistar rats].

PMID- 10925852
TI  - [Effect of selection for behavior on the hypophyseal-adrenal function in the gray
      rats Rattus norvegicus during postnatal ontogenesis].

PMID- 10925853
TI  - [Response of the mink reproduction system to the hormonal stimulation in October
      as the prognostic parameter in folliculogenesis and fertility].

PMID- 10925854
TI  - [Effect of acetazolamide on the salivary excretion of mineral ions in sheep].

PMID- 10925855
TI  - [Mechanism of the sonar detection of the echolocation target speed and
      acceleration by the dolphin Tursiops truncatus].

PMID- 10925856
TI  - [Immunohistochemical detection of the regulator cells in the leech digestive
      system].

PMID- 10925857
TI  - [Cerebral regions of the snail chemosensor systems: structural basis of the
      intersensory integration].

PMID- 10925858
TI  - [Functional classification of regulator peptides. Divergent and convergent
      evolution of regulator peptides].

PMID- 10925859
TI  - [Characteristics of deformation properties of erythrocytes from the sheep Ovis
      domesticus].

PMID- 10925860
TI  - [Ida Gavrilovna Karmanova. On the 50th anniversary of her scientific activities].

PMID- 10925861
TI  - [Vibrio cholerae O139 isolated from humans and the water from open reservoirs: a
      comparative genotyping].
AB  - The comparative study of the genomes of V. cholerae O139 isolated from humans and
      from water of surface reservoirs was carried out with the use of single- and
      double-primer polymerase chain reaction (PCR). The profiles of polymorphic DNA
      fragments obtained in this study made it possible to find out differences between
      groups of strains, as well as the individual features of some of them. The
      comparison of strains isolated from humans and from water in single-primer PCR
      revealed that they, in spite of the general similarity of their genomes,
      essentially differed, which was probably due to changes in the genome of this
      infective agent. Strains of aqueous origin lacked genes ctx and tcpA, which made
      them epidemiologically unimportant.

PMID- 10925862
TI  - [The expression of the pathogenic properties of the Vibrio cholerae O139
      serogroup in vitro].
AB  - Cholera toxin, hemolysin, dermonecrotic and proteolytic factors have been
      detected and identified in V. cholerae O139. The production of these substances
      has been found to depend on the conditions of the cultivation of vibrios, and the
      types of proteases have been determined.

PMID- 10925863
TI  - [The APUD-system function of the intestines and the morphological changes in the
      internal organs of adult rabbits infected with toxigenic Vibrio cholerae].
AB  - V. cholerae infection with clearly pronounced diarrhea was reproduced in adult
      rabbits with the use of the RITARD system. The state of the APUD system of the
      intestine of the animals and morphological changes in internal organs in
      experimental cholera were described. As noted in this study, the manifestation of
      changes in the intestine and other organs, as well as the reaction of apudocytes
      to V. cholerae infection, were linked with the intensity of diarrhea and the time
      of the death of the animals.

PMID- 10925864
TI  - [The properties of the cellular surface of Yersinia pestis strain EV and its
      achromogenic variants].
AB  - The comparative study of the properties of the surface of vaccine strain Y.
      pestis EV and its achromogenic variants (AV) differing from the initial strain by
      decreased immunogenicity and by the morphology of colonies, has been made. The
      achromogenicity of Y. pestis colonies has been shown to correlate with the loss
      of the outer membrane protein with a molecular weight 22 kD. The synthesis of
      this protein is determined by chromosomal genes. AV have been found to have
      different sensitivity to bacteriophages. The analysis of the electrokinetic
      potential of Y. pestis EV and its AV has revealed that in the latter have surface
      charge is considerably greater (1.4- to 1.5-fold). As shown in this study, the
      hemagglutinating activity of AV with respect to red blood cells of humans with
      blood group I (O) and guinea pigs is decreased by 1-2 orders and these strains do
      not agglutinate with sheep red blood cells. The low activity of the initial stage
      of the phagocytosis of AV by mouse macrophages has been shown. The possible role
      of the 22 kD proteins as an adhesion factor is discussed.

PMID- 10925865
TI  - [Listeria bacterial carriage: a method for sanative treatment].
AB  - 1.6% of clinically healthy women active in certain professions have been found to
      be carriers of pathogenic species of Listeria. The study of the sensitivity of 73
      strains of Listeria spp. to the preparations of Chlorophyllipt has revealed that
      in usual therapeutic concentrations Chlorophyllipt produces a pronounced
      antibacterial effect on these organisms. The use of Chlorophyllipt for the
      sanitation of carriers of pathogenic Listeria is proposed.

PMID- 10925866
TI  - [The action of a preparation of Escherichia coli M-17 growth autostimulants
      (Actoflor) on the growth of pure and mixed bacterial cultures].
AB  - The effect of the preparation of E. coli M-17 low-molecular exometabolites
      (Actoflor), containing growth autostimulators, on the growth of pure cultures of
      E. coli M-17 E. coli K-12, Salmonella enteritidis, Serratia marcescens and
      Bifidobacterium adolescentis MC-42 was studied. This preparation was shown to
      stimulate the growth of all above-mentioned bacteria. The addition of Actoflor
      also led to the acceleration of growth in the cultivation of mixed cultures of E.
      coli M-17 with E. coli K-12 (or S. enteritidis), the producer strain (E. coli M
      17) showing the highest degree of acceleration. Moreover, the action of Actoflor
      led to the elimination of competitor strains and to the increase of the
      antagonistic activity of E. coli M-17. Actoflor may be supposedly used as a
      therapeutic or prophylactic remedy.

PMID- 10925867
TI  - [The effect of heterologous bacilli on the infectious process in anthrax in an
      experiment].
AB  - The possibility of the survival of guinea pigs after the simultaneous
      administration of different doses of Bacillus anthracis virulent strain 81/1 in
      combination with both B. anthracis vaccine strain STI and heterologous bacilli
      (B. subtilis strain PAC) has been experimentally shown. On the basis of the
      results of these experiments suggestion has been made that the "survival
      phenomenon" is the process involving the lysosomal systems of polymorphonuclear
      and mononuclear phagocytes.

PMID- 10925868
TI  - [The antilysozyme activity of Mycobacterium tuberculosis L forms].
AB  - The method for the detection of antilysozyme activity (ALA) in M. tuberculosis L
      forms was developed. The level of ALA in M. tuberculosis L forms isolated from
      patients with different clinical forms of the disease varied within 1-5
      micrograms. M. tuberculosis L forms with the ALA level > 4 micrograms were
      isolated from patients with the progressing course of the disease. The method for
      the prognostication of the course of the tuberculous process in the lungs by the
      results of the antilysozyme test was proposed.

PMID- 10925869
TI  - [The development and testing of dried nutrient media for the demonstration of
      ureaplasmas].
AB  - The results of the development of new culture media for the indication of
      ureaplasmas are presented. The media have been developed on the basis of the
      dried nutrient broth produced by the Research and Production Amalgamation
      "Nutrient Media". The composition of the media includes Russian-made ingredients
      ensuring the growth of ureaplasmas. The physico-chemical and biological
      characteristics of the media have been perfected. The clinical trial of the newly
      developed media has been carried out in the process of the examination of 280
      pregnant women with the normal course of pregnancy, with the threat of pregnancy
      interruption and with complications of pregnancy.

PMID- 10925870
TI  - [The prevalence of helicobacteriosis in regions of Siberia based on serological
      study data].
AB  - 687 adults in 5 regions of Siberia and 79 children and young persons in
      Novosibirsk were examined. IgG antibodies to H. pylori in their blood sera were
      determined with the use the enzyme immunoassay. The detection rate of antibodies
      among the adult population varied within 70-87%, depending on the region, being
      somewhat lower among the population north of latitude 60 degrees (75%) in
      comparison with the population residing south of this latitude (86%, p < 0.001).
      In Novosibirsk the number of seropositive persons was found to be unrelated to
      sex, age and clinical manifestations of digestive tract diseases. A high
      detection rate of antibodies to H. pylori was registered in persons aged 25-34
      years with a minor increase in older age groups. In children the detection rate
      increased with age: 29% in children of 5-10 years old and 56% in children 11-14
      years old. By the age of 15 more than a half of the children had antibodies.

PMID- 10925871
TI  - [Morbidity and mortality in acute viral hepatitides in a hyperendemic region. The
      role of viral hepatitis E].
AB  - Official annual statistical data on morbidity in acute viral hepatitides (AVH),
      including the number of lethal cases, for 1985-1995 were analyzed. Mortality
      rates per 100,000 of the population at the period of 11 years were calculated for
      different age groups, sex and the place of residence. 396 and 99 patients were
      examined for the presence of serological markers of hepatitides A, B and E,
      respectively, at the periods of epidemic rises in morbidity and satisfactory
      epidemic situation. In the course of 11 years AVH caused the death of 22,405
      persons. In 1985-1987 the average mortality level (ML) reached 12.3-17.8 per
      100,000 of the population (with morbidity being 1,200-1,400 and was essentially
      higher among the rural population in comparison with the urban population. During
      these years the highest ML, was registered among children aged 0-2 years (190-50
      per 100,000) and, among adults, mainly among women aged 20-29 years (21.4-19.6
      per 100,000). During the years when the epidemic of AVH was absent, ML among
      these groups was essentially lower: 40-20 among children aged 0-2 years and 4-5
      among women aged 20-29 years. In 1987 in the Fergana Valley hepatitis E was
      detected in 72.2% of all examined patients, and in the southern areas of the
      country in 68.7%. A sharp rise on mortality among women of the productive age at
      the period of the epidemic rise of AVH morbidity in the endemic region indicated
      that this epidemic was linked with hepatitis E. High ML among young children may
      be indicative of a highly unfavorable course of hepatitis E in the group of
      infants, which had never been registered before. This newly established
      regularity may be used for the retrospective diagnostics of the outbreak of
      hepatitis E.

PMID- 10925872
TI  - [The colonization of plants by Yersinia pestis EV in an experiment].
AB  - The penetration of Y. pestis (strain EV) into the stem of Impatiens walleriana
      via its roots, submerged into microbial suspension, was observed under
      experimental conditions. This was indicative of the colonization of plants by Y.
      pestis, thus confirming the possibility of their preservation in plants during
      periods between epizootics at the territories of natural foci.

PMID- 10925873
TI  - [The protective role of postvaccinal immunity in mumps in children].
AB  - The immunological study of children with infectious parotitis (IP) without
      complications and with such complications as pancreatitis, meningitis or orchitis
      in the glandular form was carried out. In accordance with the previously proposed
      principle, 4 types of immune response (IR) were established on the basis of
      differences in initial resistance and the IR profile: cell-mediated immunity
      (types I and III) and humoral immunity (types II and IV). The patients included
      nonvaccinated children, as well as children vaccinated on epidemic indications, 3
      6, 7-9, 10 and more years before infection. The comparative analysis of the
      number of IP cases with and without complications in the groups of children,
      divided according to their immunization history and the type of IR, revealed that
      postvaccinal immunity in children vaccinated on epidemic indications (less than a
      month ago) or 3-6 years before infection had protective potential, sufficient for
      the prevention of complicated forms of IP. Immunity obtained 7-9 years ago was
      effective for the protection from IP complications only in cell-mediated, but not
      humoral IR. Postvaccinal immunity obtained more than 10 years ago did not ensure
      the decrease in the occurrence of complicated forms of IP (in comparison with
      that in nonvaccinated patients) in children with any type of IR.

PMID- 10925874
TI  - [Strains of Vibrio cholerae serogroups O1 and O139 that produce the basic
      protective antigens].
AB  - To find out stable and effective producers of major protective antigens intended
      for use as components of cholera chemical vaccine against V. cholerae strains of
      serogroups O and O139, the comparative analysis of the production of cholera
      toxin, toxin-coregulated pili (TCP), antigens O1 and O139, polysaccharide capsule
      and outer membrane protein OmpU in different V. cholerae strains groups O1 and
      O139 has been made. V. cholerae strain KM68, serogroup O1, has been found capable
      of the production of antigen O1, serovar Ogawa, protein OmpU at a sufficiently
      high level and the hyperproduction of cholera toxin and TCP, and thus suitable
      for use in the manufacture of cholera bivalent vaccine as the source of these
      antigens. Specially selected alysogenic noncapsular strain KM137 of serogroup
      O139, characterized by a high and stable level of the biosynthesis of this
      somatic antigen when grown in both laboratory and production conditions, may
      serve as the produces of antigen O139.

PMID- 10925875
TI  - [The goals of the World Health Organization in the vaccinal prophylaxis of
      measles and rubella].

PMID- 10925876
TI  - [The characteristics of the development of immunity with a primary immunization
      complex using adsorbed DTP vaccine].
AB  - The intensity of immunity, depending on immune response variants characterized by
      the definite composition of the T and B lymphocyte subpopulation in peripheral
      blood, was studied in 70 practically healthy young children after the primary
      complex of immunization with adsorbed DPT vaccine. The most stable immune
      reaction was shown to appear in children with the hyperergic and normoergic
      variants of immune response to diphtheria and tetanus toxoids, while the reaction
      to pertussis antigen was essentially weaker both after the second vaccination and
      after the first revaccination. In children with the hypoergic variant of immune
      response to all components of adsorbed DPT vaccine the resulting immune reaction
      was 2.5-3 times weaker than in children of other groups.

PMID- 10925877
TI  - [Antibodies to meningococcal antibodies in the sera of patients and donors].
AB  - The comparative study of sera taken from healthy persons (pooled sera of 100
      donors, 6 individual serum specimens) and sera taken from patients with
      meningococcal meningitis (pooled sera of 10 patients with meningococcal
      infection, group A, and 6 individual serum specimens from patients with
      meningococcal infection, groups A, B, C) was carried out by the method of
      immunoblotting. All proteins from healthy donors were found to contain antibodies
      to meningococcal iron-regulated protein (IRP) of 85 kD, designated as TbpB. In
      30% of donor sera the presence of antibodies to meningococcal IRP of 34 kD (FbpA)
      was registered. Moreover, donor sera were found to contain antibodies to
      meningococcal IRP of 45 kD. The sera taken from convalescents were found to have
      the increased content of antibodies to IRP of 70 and 85 kD and somewhat lesser
      content of antibodies to proteins of 98, 44 and 34 kD. As regards other (non iron
      regulated) proteins, in the process of convalescence the most intensive antibody
      production was observed with respect to minor protein with a molecular weight of
      50 kD, as well as proteins of class 5, characterized by molecular weights of 30
      kD and less.

PMID- 10925878
TI  - [The use of monoclonal antibodies for detecting the common antigenic determinants
      of Brucella spp. and Yersinia enterocolitica O:9].
AB  - Monoclonal antibodies (McAb) 2AH10, specifically reacting with protein
      preparations having mol. wt. of 18 and 38 kD and not interacting with brucellar
      lipopolysaccharide (LPS) and protein-polysaccharide antigen, have been obtained.
      As shown with the use of McAb 2AH10, Brucella spp. and Yersinia enterocolitica
      O:9 possess common antigenic determinants, localized not only in the area of
      their LPS, which is generally known, but also in the area of their outer cell
      wall proteins with mol. wt. 18 and 38 kD. The sensitivity of the solid-phase
      enzyme immunoassay and the latex agglutination test with the use of McAb 2AH10 is
      essentially higher in the detection of B. abortus and B. suis, than B. melitensis
      and B. rangiferi, as well as Y. enterocolitica O:9. Essential differences
      observed in the detected concentrations of different Brucella species and Y.
      enterocolitica O:9 are seemingly linked with different expression of specific
      antigenic determinants, detected with the use of McAb 2AH10 in the corpuscular
      antigens under study.

PMID- 10925879
TI  - [An allergen from Blattella germanica cockroaches and its immunological
      properties].
AB  - The optimum method for obtaining allergenic preparation with high specific
      activity and stable physico-chemical characteristics from cockroaches of the
      species B. germanica was developed. The quantitative content of cockroach
      allergens Bla g1 and Bla g2 was determined in experimental batches. The age
      structure of sensitization to cockroaches in 124 bronchial asthma patients (50
      adults and 74 children) was studied. Specific IgE antibodies to B. germanica were
      detected in 34% of the examined adults and 63.5% of the children.

PMID- 10925880
TI  - [The possibility of using the data on the content of volatile fatty acids for the
      indirect demonstration of the causative agents of suppurative-inflammatory
      diseases in the pathological material].
AB  - The use of the quantitative content of volatile fatty acids as marker for the
      indication of the causative agents of pyo-inflammatory diseases in material taken
      from wounds is proposed. Thus, in 71% of cases the detection of acetic acid in a
      purulent wound coincided with the bacteriological isolation of monocultures, as
      well as associations, of facultative anaerobic bacteria. The analysis of
      isobutyric, butyric, isovaleric, valeric and acetic acids permitted the rapid
      detection of associations of obligate and facultative anaerobic bacteria in an
      individual patient. Changes in the quantitative content of volatile fatty acids
      in pathological material integrally reflected the dynamics of the causative
      agents of purulent infections and the effectiveness of the prescribed therapy.

PMID- 10925881
TI  - [Changes in the cell size of Escherichia coli M-17 during induced destruction].
AB  - The autolysis of E. coli, induced by their deprivation of nutrition in
      combination with the action of oleic acid and a temperature of 45 degrees C, was
      studied. The study revealed that an increase in the number of cells during 4
      hours after the induction of the process was accompanied by a decrease in their
      size and an increase in the surface/volume ratio. Changes in the size of bacteria
      in the course of induced destruction resulting from their deprivation of
      nutrition in combination the action of oleic acid and a temperature of 45 degrees
      C were found to occur in two phases: (1) a decrease in size with an increase in
      the surface/volume ratio; (2) an increase in size with a decrease in the
      surface/volume ratio.

PMID- 10925882
TI  - [The role of capsule formation in Burkholderia mallei for its persistence in
      vivo].
AB  - When studied in vivo (in guinea pigs) with the use of electron microscopy, B.
      mallei (strains C-5, 10230) were found to form a capsule. In the subacute course
      of infection, the encapsulated forms of B. mallei parasitized mainly in the cells
      of the system of mononuclear phagocytes in the liver, the spleen and the lungs.
      The capsule formed by B. mallei was shown to be one of the factors facilitating
      its persistence in the body.

PMID- 10925883
TI  - [The efficacy of immunizing children who are forced migrants against diphtheria
      and tetanus based on the results of serological studies].
AB  - The results of the serological study of 2,352 children aged 1-6 years who had
      arrived to the territory of the region without any documents on past immunization
      revealed that most of these children had sufficiently pronounced specific
      immunity to diphtheria (66.4%) and tetanus (83.6%) Thus the tactics of the
      prophylactic immunization of children having no relevant documents must be worked
      out with due regard to the results of serological studies.

PMID- 10925884
TI  - [The possible role of alpha 2-macroglobulin in regulating the immune components
      of the brain in tick-borne encephalitis].
AB  - In tick-borne encephalitis certain immunopathological reactions develop in the
      tissues of the central nervous system; alpha 2-macroglobulin may serve as the
      marker of the activity of these reactions. The dynamic study of liquor taken from
      16 patients with the meningeal and focal forms of tick-borne encephalitis (TBE),
      8 patients with severe craniocerebral traumas accompanied by meningitis and 10
      patients with osteochondrosis was made. As revealed in this study, in TBE
      patients the level of alpha 2-macroglobulin increases 3.5-fold and remains stable
      during the acute period of the disease.

PMID- 10925885
TI  - [The clinical immunogenetics of viral hepatitis C in a Caucasoid population of
      western Siberia].
AB  - The analysis of the immunogenetic studies on hepatitis C patients among the
      Caucasoid population of western Siberia has revealed a significant increase in
      the detection rate of antigens HLA-A10 and HLA-DR5, the combinations of DR2-DR5,
      DR5-DR7, DR1-B27 and the complete absence of antigen HLA-DR4, which is indicative
      of the fact that susceptibility and resistance to the development of the disease
      is associated with the genes of the main histocompatibility complex. In hepatitis
      of mixed etiology, B and C, a significant increase in the occurrence of HLA
      antigens: -A1, -B8, -DR1 and -DR3, as well as the combinations of A1-DR1, A1-DR3,
      A3-DR3, A9-A10, DR1-DR3, B8-DR3 is noted; at the same time a decrease in the
      occurrence of antigen DR4 and its combination with antigen HLA-A2 is observed.

PMID- 10925886
TI  - [The results of a 5-year study of listeriosis in Ukraine].
AB  - Data on the isolation of Listeria spp. cultures on the territory of Ukraine, the
      frequency of Listeria contamination of alimentary raw materials and foodstuffs,
      the level of listeriosis morbidity, the clinical forms of the manifestation of
      this disease, as well as the occurrence of asymptomatic carriership among
      clinically healthy persons of epidemiologically significant professions, are
      given. The results of the study of the biological properties of 73 strains of
      Listeria spp., their sensitivity to antibiotics and Chlorophyllipt are presented.

PMID- 10925887
TI  - [The characteristics of biological preparations and food additives for functional
      nutrition and the correction of the intestinal microflora].

PMID- 10925888
TI  - [The ecological and medical aspects of the symbiosis between Escherichia coli and
      man].
AB  - In this work different variants of the symbiosis of E. coli with a human body are
      analyzed, and the symbiotic relationships between them are shown to follow the
      type mutualism, commensalism, parasitism and habitation. The authors emphasize
      that the multiplicity of variants of bacteria-host relationships is based on the
      phenotypic polymorphism of E. coli clones (clone lines). Taking into account
      their ecological (symbiotic) features and biomedical importance, all E. coli
      clones are divided into 4 groups (clusters): mutualists as nonpathogenic
      organisms; commensals as potential pathogens (causing extraintestinal E. coli
      infections); parasites as real pathogens (causing acute intestinal infections);
      "occasional" symbionts of man. The proposition on the cluster structure of E.
      coli as a species is formulated.

PMID- 10925889
TI  - [Variants of Yersinia pestis resistant to a diagnostic bacteriophage and the
      problems related to them].
AB  - The data of literature on the pleiotropic variability of the resistance of Y.
      pestis mutants to diagnostic phage are presented. The conditions of reversion to
      the initial phenotype are characterized. The mechanisms of the appearance of such
      variability of Y. pestis, as well as problems arising in connection with this
      variability and linked with the pathogenic activity of Y. pestis, low
      effectiveness of the diagnostic methods used in the inspection of the natural
      foci of plaque, the reservation of microbes in nature during the periods between
      epidemics, are discussed.

PMID- 10925890
TI  - [The epidemiology of acute intestinal infections complicated by the development
      of the hemolytic-uremic syndrome in Tula Province].

PMID- 10925892
TI  - [An analysis of tick-borne borreliosis morbidity in the city of Ul'ianovsk during
      1996-1998].

PMID- 10925893
TI  - [Viral hepatitis B as an occupational disease of medical workers].

PMID- 10925894
TI  - [Epidemic parotitis: the outlook for decreasing its morbidity].

PMID- 10925895
TI  - [The managers of the epidemic-control service at the fronts and in the fleets in
      World War II (on the 55th anniversary of the Great Victory)].

PMID- 10925891
TI  - [The etiology, clinical picture and epidemiology of a group respiratory infection
      in the children of Khabarovsk Territory].

PMID- 10925896
TI  - Pregnancy and the impact of inherited thrombophilias.

PMID- 10925897
TI  - The management of endometrial carcinoma.

PMID- 10925898
TI  - Future trends in human reproduction.

PMID- 10925900
TI  - The detection, investigation and management of hypertension in pregnancy: full
      consensus statement.

PMID- 10925899
TI  - The detection, investigation and management of hypertension in pregnancy:
      executive summary.

PMID- 10925901
TI  - Uptake of Down syndrome screening in an Australian Vietnamese population.
AB  - It has been previously shown that the uptake of prenatal diagnosis by Victorian
      women of a non-English speaking background is significantly lower than that of
      comparable English speaking women. To explore this further we have examined the
      uptake of Down syndrome screening and diagnosis by Vietnamese women attending a
      community-based antenatal clinic in metropolitan Melbourne over a two year
      period. Of the 207 women studied, 161 (78%) were offered screening or diagnosis
      and of these women 139 (86%, 95%CI 81-92%) accepted the offer, representing 67%
      (95%CI 61-74%) of the entire population. Of the 127 women who had screening,
      rather than diagnosis, 12 (9%) had an 'increased risk' result. Eleven of these
      women accepted diagnosis. We also explored the reasons why 45 (22%) of women were
      not offered screening. Almost half (44%) of these women first attended the clinic
      at a too advanced stage of gestation but in 25 women there were no obvious
      reasons. These results are discussed in the context of current prenatal screening
      and diagnostic practice in Victoria and simple recommendations made.

PMID- 10925902
TI  - Development of a customised birthweight standard for ethnic Chinese subjects.
AB  - A model to establish customised birthweight standards for the Chinese population
      was developed, using data from a cohort of 1564 Chinese women with normal
      singleton pregnancies. Multiple regression analysis was performed using maternal
      height, weight, parity, gestation at delivery and fetal sex as independent
      (predictor) variables. From this, a customised ideal birthweight for each baby
      can be estimated, and the normality of the actual birthweight can be evaluated
      according to this, rather than from population standards. The results of this
      study show that birthweights are strongly influenced by maternal characteristics,
      confirming conclusions from similar studies in other ethnic populations. The
      overall mean birthweight at 280 days of gestation was 3252 g, which was smaller
      than that of the Caucasian population. Birthweight increased with maternal height
      (5.1 g/cm), maternal booking weight (10.2 g/kg) and gestation at delivery (18.3
      g/day from 280 days). Babies from women who had two previous deliveries weighed
      145.2 g more than the nulliparous. Male babies were 84.8 g heavier than females.
      Adjustment using these results produces a customised ideal birthweight for each
      baby. When compared with population based standards, customised birthweight
      standards identified significantly fewer small for gestational age (SGA -
      birthweight below 10th centile, McNemar Chi square = 19.1, p < 0.01) and fewer
      large for gestational age (LGA - birthweight above 90th centile, McNemar Chi
      square = 23.7, p < 0.01) cases.

PMID- 10925903
TI  - Patterns of medication use during and prior to pregnancy: the MAP study.
AB  - We interviewed 140 pregnant women of any gestational age attending antenatal
      clinics at the Women's and Children's Hospital in Adelaide during September
      October 1999 to elicit information about their patterns of medication use during
      and in the 3 months prior to their current pregnancy. Demographic information,
      information on women's prescribed, non-prescribed, and non-medicinal drug use
      during and in the 3 months prior to pregnancy, and information about both their
      general sources of information on medication use and their specific reasons for
      medication uptake/cessation during pregnancy were obtained. The women used an
      average of 0.7 0.8 prescribed and 2.3-2.6 non-prescribed medications (total 3.1
      3.3) in the 3 pregnancy trimesters, compared with 1.0 prescribed and 2.2 non
      prescribed prior to pregnancy. Use of a prescribed or non-prescribed medication
      was 96-97% across trimesters. Simple analgesics, vitamin/mineral supplements, and
      antacids were the most commonly taken medications. Antibiotics were the most
      commonly prescribed medication. Use of class A medications increased during
      pregnancy while use of non-class A medications decreased. Peri-conceptional
      folate supplementation was 31%. Alcohol consumption and cigarette smoking
      decreased after diagnosis of pregnancy. Both prescribed and non-prescribed
      medication use is common during all trimesters of pregnancy. However, overall use
      changes little compared with pre-pregnancy values. Rates of peri-conceptional
      folate supplementation are low.

PMID- 10925904
TI  - Sources of advice on medication use in pregnancy and reasons for medication
      uptake and cessation during pregnancy.

PMID- 10925905
TI  - Investigation and management of fetomaternal alloimmune thrombocytopenia.

PMID- 10925906
TI  - Estimation of fetal weight by ultrasound prior to 33 weeks gestation.
AB  - The aim of this study was to develop an accurate formula for the ultrasonic
      prediction of fetal weight for infants < 33 weeks gestational age and < or = 1500
      g birthweight. The subjects comprised live births free of lethal malformations or
      chromosomal anomalies, < 33 weeks gestational age and with birthweights +/- 1500
      g born in the Royal Women's Hospital between January 1990 and March 1996. All
      subjects had accurate gestational age confirmed by ultrasound prior to 20 weeks
      gestation and ultrasound measurements within 72 hours of birth of biparietal
      diameter (BPD), femur length (FL) and abdominal circumference (AC). A formula
      with the highest explained variance was computed by linear regression analysis
      using the three fetal variables in various combinations from 54 infants born
      between January 1990 and December 1993. The optimal formula was:
      Log(10)birthweight = 0.714627 + 0.077362.AC + 0.058758.BPD + 0.287037.FL -
      0.011274.AC.FL. The new formula was more accurate compared with existing formulae
      when tested in a separate cohort of 39 infants born between January 1994 and
      March 1996.

PMID- 10925907
TI  - Factor V Leiden as a risk factor for miscarriage and reduced fertility.
AB  - The Leiden mutation is a recent discovery. It is the main cause of inherited
      thrombophilia and has been found in 20-60% of deep vein thrombosis cases. More
      recently it has been found in a significant number of cases of obstetric
      complications attributable to placental thrombosis. Current patient management
      practice for dealing with the Leiden mutation is based mainly on information
      about deep vein thrombosis because there is little information on pregnancy
      complications. There are no prospective studies examining the risk of developing
      pregnancy complications for Leiden mutation carriers. The aim of this study is to
      do that by comparing the frequency of unfavourable pregnancy outcomes among
      carriers with those among controls. The number of women developing miscarriages,
      intrauterine deaths, or infertility problems among 128 Leiden mutation carriers
      was compared with the number among 461 controls. The risk of having at least one
      miscarriage or infertility problems was 1.5 times greater for Leiden mutation
      carriers than controls. This result was statistically significant (95% CI 1.2,
      2.7). The risk of having at least two miscarriages or infertility problems was
      2.5 times greater for Leiden mutation carriers than controls. This was also
      statistically significant (95% CI 1.2, 5.13).

PMID- 10925908
TI  - Endometrial adenocarcinoma--presenting pathology is a poor guide to surgical
      management.
AB  - We aimed to evaluate the correlation between the histological grade of
      endometrial cancer diagnosed on endometrial biopsy or curettage, with the
      definitive grade and stage of lesion as determined by surgery and
      histopathological examination and to make recommendations about the suitability
      of conservative surgery based on pre-operative determination of the grade of
      endometrial adenocarcinoma. A retrospective review of all patients with
      endometrial adenocarcinoma presenting to the Queensland Centre for Gynaecological
      Cancer from 1 January 1996 to 31 December 1998 was undertaken. Clinical and
      pathological data was abstracted from medical records and case notes of 460
      patients. All histological specimens were prospectively reviewed by a panel
      consisting of gynaecologic pathologists, gynaecologic oncologists and other
      doctors involved in the treatment of patients with gynaecological malignancies.
      The percentage of patients whose management would have been optimised by full
      surgical staging at the time of initial surgery was calculated. Only 60%, 71%,
      and 84 % of the patients with a presenting diagnosis of grade 1, 2 and 3
      endometrial adenocarcinomas respectively had this confirmed on final
      histopathology. Furthermore, using established criteria, 30%, 46% and 100% of
      patients presenting with grade 1, 2 and 3 endometrial adenocarcinoma required
      full surgical staging at the time of their primary surgery There is poor
      correlation between the pre-operative grade of endometrial cancer and the grade
      as determined on analysis of the resected uterus. The correlation is poorest with
      grade 1 endometrial adenocarcinoma, where strongest consideration is given to
      conservative surgery and the avoidance of subspecialty referral. There is a
      strong argument that all patients with a diagnosis of endometrial cancer made on
      endometrial biopsy or curettage, regardless of grade of malignancy, should be
      offered surgery where the option to perform concurrent comprehensive surgical
      staging is available.

PMID- 10925909
TI  - Knowledge and attitudes about vaginal birth after Caesarean section in Australian
      hospitals. VBAC Study Group. Vaginal Birth After Caesarean.
AB  - A survey of staff attitudes and knowledge about vaginal birth after Caesarean
      section (VBAC) was undertaken in Australian hospitals. There was a high response
      rate (67%), and over 900 responses were analysed. Generally, there was a high
      level of awareness about outcomes and the relative importance of many issues in
      considering VBAC. Registrars, consultants and midwives differed significantly in
      some aspects of their knowledge and attitudes to VBAC. There was also a wide
      range of opinion within each group. Approximately half (53%) of respondents
      believed patients should be actively encouraged to consider VBAC, whereas 47%
      felt it should be simply presented as an option.

PMID- 10925910
TI  - Successful pregnancy outcome following first trimester pelvic inflammatory
      disease.
AB  - Pelvic inflammatory disease rarely complicates pregnancy. Although few in number,
      most of the previously reported cases have resulted in spontaneous abortion or
      intrauterine fetal demise. At 5 weeks gestation, a 20 year old gravida 2 para 1
      underwent uterine curettage and diagnostic laparoscopy for a suspected ectopic
      gestation. Seventeen days later, she presented with severe bilateral lower
      abdominal pain, cervical motion tenderness, uterine tenderness, and bilateral
      adnexal tenderness. After 84 hours of intravenous cefazolin, gentamycin, and
      clindamycin, the patient had resolution of all symptoms. She then completed 14
      days of outpatient antibiotic therapy with oral cephalexin. At 39 weeks
      gestation, she delivered a 3611 g male fetus via spontaneous vaginal delivery.
      Successful pregnancy outcome can occur after first trimester pelvic inflammatory
      disease.

PMID- 10925911
TI  - Multiple obstetric complications of factor V Leiden mutation.

PMID- 10925912
TI  - Urachal abscess and infected bladder diverticulum.
AB  - Urachal abscess is an uncommon condition with protean features and often presents
      a diagnostic challenge to clinicians. This case report describes a 41-year-old
      woman with severe multiple sclerosis who was referred to a gynaecological
      oncology service with the presumed diagnosis of advanced ovarian cancer. A
      diagnosis of urachal abscess and infected bladder diverticulum was made by a
      combination of imaging modalities and a percutaneous biopsy. It is important to
      be aware of this entity, as the presentation varies widely and when diagnosed
      early the condition may be treated appropriately by relatively minor surgical
      intervention.

PMID- 10925913
TI  - Spontaneous uterine perforation from uterine infarction: a rare case of acute
      abdomen.
AB  - A case of spontaneous uterine perforation from uterine infarction is presented.
      The authors believe that this is the first reported case.

PMID- 10925914
TI  - Isolated torsion of the Fallopian tube.

PMID- 10925915
TI  - Partial mole, triploidy and proteinuric hypertension: two case reports.
AB  - We present two cases of proteinuric hypertension in the early second trimester of
      pregnancy, associated with partial mole and triploidy karyotyping. This
      demonstrates the complementary nature of ultrasound in the diagnosis and
      management of this rare association.

PMID- 10925916
TI  - Vesicocervical fistula: an unusual presentation.
AB  - A rare case is presented of vesicocervical fistula that occurred in a woman who
      sought help for continuous dribbling of urine for nine years. The aetiological
      implications of her obstetric history are discussed in the context of previous
      reports in the literature. The management and outcome of this case is discussed.

PMID- 10925917
TI  - Ovarian cancer developing in the ovarian remnant syndrome. A case report and
      literature review.

PMID- 10925918
TI  - Advanced stage of dysgerminoma in testicular feminisation: is radical surgery
      necessary?

PMID- 10925919
TI  - Relative safety of vacuum extraction vs Kielland forceps delivery.

PMID- 10925920
TI  - Current obstetric training programs are unlikely to provide registrars with
      sufficient skill in the safe use of Kielland forceps.

PMID- 10925921
TI  - The practice of instrumental delivery at Kandang Kerbau Hospital in Singapore.

PMID- 10925922
TI  - Double standards on Caesareans and abortions for non-medical indications.

PMID- 10925923
TI  - The misplace of litigation in medical practice.

PMID- 10925924
TI  - Label fusion.

PMID- 10925925
TI  - Prolonged actions of short-acting drugs: local anesthetics and chronic pain.

PMID- 10925926
TI  - Interscalene block: the truth about twitches.

PMID- 10925927
TI  - How should we handle epidural solutions? One view.

PMID- 10925928
TI  - Why are postdural puncture headaches still a problem?

PMID- 10925930
TI  - Interscalene block with a nerve stimulator: a deltoid motor response is a
      satisfactory endpoint for successful block.
AB  - BACKGROUND AND OBJECTIVES: The interscalene brachial plexus block (ISB) is an
      effective and well-established anesthetic technique for shoulder surgery. Using
      nerve stimulation as an aid in block placement, a motor response (twitch) in the
      biceps or a more distal upper limb muscle has been recommended to indicate
      accurate needle placement. Our clinical experience, as well as anatomic
      reasoning, suggests that a deltoid twitch may be just as effective as one in the
      biceps for predicting successful block. This prospective clinical study was
      undertaken to compare a deltoid with a biceps twitch with respect to onset and
      success of motor block. METHODS: A total of 160 patients scheduled for shoulder
      surgery were studied prospectively. Interscalene blocks were performed using
      neurostimulation according to our standard technique. Twitches of the deltoid or
      biceps or both, whichever appeared first, were accepted and used as the endpoint
      for needle placement and injection of local anesthetic. Motor block success,
      i.e., patient inability to lift the arm against gravity, and minutes to motor
      block onset were recorded. RESULTS: There was 1 failed motor block in the deltoid
      group and none in the other groups (not a statistically significant difference).
      When the same local anesthetic was used, there were no statistically significant
      differences in onset times between the biceps, deltoid, or biceps/deltoid groups.
      CONCLUSIONS: A deltoid twitch is as effective as a biceps twitch in determining
      accurate needle placement for ISB and in predicting successful motor block.
      Acceptance of a deltoid twitch during ISB eliminates the need for further probing
      and may translate into better patient acceptance and in a smaller risk of needle
      induced nerve damage.

PMID- 10925929
TI  - EMLA reduces acute and chronic pain after breast surgery for cancer.
AB  - BACKGROUND AND OBJECTIVES: A significant percentage of women undergoing breast
      surgery for cancer may develop neuropathic pain in the chest, and/or ipsilateral
      axilla and/or upper medial arm, with impairment in performing daily occupational
      activities. We designed this study to determine if the perioperative application
      of EMLA (eutectic mixture of local anesthetics; AstraZeneca) cream in the breast
      and axilla area reduces analgesic requirements, as well as the acute and chronic
      pain after breast surgery. METHODS: Forty-six female patients scheduled for
      breast surgery received randomly 5 g of EMLA or placebo on the sternal area 5
      minutes before surgery, and 15 g on the supraclavicular area and axilla at the
      end of the operation. Treatment with EMLA cream (20 g) or placebo was also
      applied daily on the 4 days after surgery. In the postanesthesia care unit
      (PACU), 3, 6, 9, and 24 hours after surgery, and on the second to sixth day
      postoperatively, pain was assessed by visual analogue scale (VAS) at rest and
      after movement, and postoperative analgesic requirements were recorded. Three
      months later, patients were asked if they had pain in the chest wall, axilla
      and/or medial upper arm, decreased sensation, if they required analgesics at
      home, and for the intensity of pain. RESULTS: Acute pain at rest and with
      movement did not differ between the EMLA and control groups, and the analgesics
      consumed during the first 24 hours were the same for the EMLA and control groups.
      However, time to the first analgesia requirement was longer (P = .04), and
      codeine and paracetamol consumption during the second to fifth days was less (P =
      .001, and P = .004, respectively) in the EMLA versus the control group. Three
      months postoperatively, pain in the chest wall, axilla, and the total incidence
      and the intensity of chronic pain were significantly less in the EMLA versus the
      control group (P = .004, P = .025, P = .002 and P = .003, respectively). The use
      of analgesics at home and abnormal sensations did not differ between the 2
      groups. CONCLUSIONS: The application of EMLA to patients undergoing breast
      surgery for cancer reduced the postoperative analgesic requirements and the
      incidence and intensity of chronic pain.

PMID- 10925931
TI  - Epidural catheter tip cultures: results of a 4-year audit and implications for
      clinical practice.
AB  - BACKGROUND AND OBJECTIVES: The aims of this study were to evaluate the clinical
      relevance of routine microbiological culture of epidural catheter tips after use
      in acute pain management, and to identify patterns of culture result with respect
      to both indications for, and duration of, epidural catheterization. METHODS: The
      Acute Pain Service (APS) reviews all patients under its care at least daily and
      keeps detailed records on each. Over a 4-year period, when APS protocol required
      epidural catheter tips to be sent for microbiological culture on removal, the APS
      saw 1,810 patients who had received epidural analgesia. The records of these
      patients were reviewed. RESULTS: Culture results were available for 1,443 (79.7%)
      patients: 1,027 catheter tips (71.2%) were sterile, while 416 (28.8%) were
      positive for at least 1 type of microorganism. Clinically, no epidural space
      infections were identified. The highest positive culture rates were found from
      epidural catheters used in the treatment of pain from fractured ribs or fractured
      pelves, while the lowest incidences occurred in elective orthopedic and thoracic
      surgery. The proportion of epidural catheters with positive culture results
      steadily increased with the duration of catheterization, but there were no
      clinically significant differences for catheters left in situ for either 3 or 4
      days. CONCLUSIONS: We concluded that a significant proportion of epidural
      catheter tips may be "culture positive" after removal. It is suggested that this
      probably represents colonization of the skin at the catheter insertion site and
      subsequent contamination of the catheter tip on removal of the catheter. The
      large number of "culture positive" tips in the absence of clinically identifiable
      epidural space infection suggests that routine culture of epidural catheter tips
      is clinically irrelevant in the vast majority of cases, and that it is not a good
      predictor of the presence of an epidural space infection.

PMID- 10925932
TI  - Sterility of epidural solutions--recommendations for cost-effective use.
AB  - BACKGROUND AND OBJECTIVES: Specific recommendations or guidelines for duration of
      use or "hangtime" for epidural solutions have not been established. Presently,
      most hospital policies limit expiration dating of these solutions to 24 hours at
      room temperature. Extending expiration dating would reduce or eliminate the
      manipulation of the epidural system during the course of therapy. The objective
      of this study was to assess the bacteriologic status over time of pharmacy
      prepared epidural solutions to determine if longer expiration dating could be
      safely instituted. METHODS: Samples from both previously administered and
      nonadministered bags of epidural infusate solutions were retrieved for
      bacteriologic testing and maintained at room temperature. These solutions were
      tested every 5 to 7 days beginning 24 to 48 hours after preparation. RESULTS:
      Samples of 54 infusion bags were tested for a median duration of 63 days. One
      hundred fifteen samples were tested. Only 5 samples of 4 solutions reported
      positive cultures; no growth was reported for multiple subsequent cultures of
      these solutions. CONCLUSIONS: Samples of pharmacy-prepared epidural solutions
      remained sterile for greater than 42 days. A change from epidural solution
      expiration dating of 24 hours to 48 or 72 hours would translate into a cost
      savings of $36,375 to $48,450 at our institution.

PMID- 10925933
TI  - Neurotoxicity of intrathecally administered tetracaine commences at the posterior
      roots near entry into the spinal cord.
AB  - BACKGROUND AND OBJECTIVES: Neurotoxicity of intrathecally administered local
      anesthetics is generating increased interest. This study was designed to examine
      the histopathologic effects of intrathecally administered tetracaine. METHODS:
      Sixty Wistar rats randomly received either 20%, 10%, 5%, 3%, 1%, 0.5%, or 0%
      tetracaine dissolved in 10% glucose solution or no solution via a chronically
      implanted intrathecal catheter. The spinal cord at L1, posterior and anterior
      roots and cauda equina were excised 5 days later, sectioned, processed, and
      prepared for light and electron microscopic examinations. RESULTS: Rats treated
      with tetracaine at 10% or 20% developed lesions in the posterior white matter and
      posterior roots. Rats injected with 3% or 5% tetracaine developed lesions, which
      began in the posterior roots close to the spinal cord and extended to the
      posterior white matter. The lesions were characterized by axonal degeneration.
      Injections of < or =1% of tetracaine did not cause any pathological changes.
      CONCLUSIONS: Our results suggest that the initial target of intrathecal
      tetracaine neurotoxicity may be the posterior roots at their entry into the
      spinal cord, where the axons are devoid of myelin sheath and thus representing a
      sensitive area for neurotoxic change.

PMID- 10925934
TI  - Respiratory gas exchange and hemodynamics during lumbar epidural anesthesia:
      effects of lidocaine with and without epinephrine.
AB  - BACKGROUND AND OBJECTIVES: Epinephrine modifies the hemodynamic response to
      epidural local anesthetic; effects on respiratory gas exchange are not known. We
      hypothesized that epidural epinephrine would increase oxygen consumption and
      carbon dioxide production. METHODS: Twelve healthy patients (age, 22 to 46 years)
      undergoing surgery on the knee were randomly assigned to receive either 2%
      lidocaine (group L) or 2% lidocaine with epinephrine 5 microg x mL(-1) (group E),
      approximately 20 mL, over 10 minutes via lumbar epidural catheter. Total-body
      oxygen consumption (VO2) and carbon dioxide production (VCO2) were determined by
      indirect calorimetry; hemodynamic measurements were obtained by noninvasive
      thoracic electrical bioimpedance. Values of VO2, VCO2, heart rate (HR), cardiac
      index (CI), and mean arterial blood pressure (MAP) were determined every minute
      and averaged every 5 minutes for 30 minutes. Comparisons were made with analysis
      of variance (ANOVA) (within groups) and t-tests (between groups). Differences
      were considered statistically significant if P < .05. RESULTS: VO2 did not change
      in either group, while VCO2 increased significantly by 22% at 20 minutes in group
      E. Increases in HR were apparent in both groups, with significantly greater
      increases in group E (group L, 13%; group E, 21%). CI did not change in group L,
      but increased by 41% in group E. MAP decreased significantly by 11% in group E,
      but did not change in group L. CONCLUSIONS: The addition of epinephrine, 5 microg
      x mL(-1), to the epidural injection of 2% lidocaine is associated with changes
      not only in hemodynamics, but also in respiratory gas exchange.

PMID- 10925935
TI  - Generating a learning curve for pediatric caudal epidural blocks: an empirical
      evaluation of technical skills in novice and experienced anesthetists.
AB  - BACKGROUND AND OBJECTIVES: Learning curves for anesthesia procedures in adult
      patients have been determined, but no data are available on procedures in
      pediatric anesthesia. The aim of this study was to assess the number of caudal
      blocks needed to guarantee a high success rate in performing caudal epidural
      analgesia in children. METHODS: At a teaching hospital, the technical skills of 7
      residents in anesthesiology who performed caudal blocks were evaluated during 4
      months using a standardized self-evaluation questionnaire. At the start of the
      study period, the residents had no prior experience in pediatric anesthesia or in
      performing caudal epidural blocks. All residents entered the pediatric rotation
      after a minimum of 1 year of training in adult general and regional anesthesia.
      The blocks were rated using a binary score. For comparison, the success rates of
      8 experienced staff anesthesiologists were collected during the same period using
      the same self-evaluation questionnaire. Statistical analyses were performed by
      generating individual and institutional learning curves using the pooled data.
      The learning curves were calculated with the aid of a least-square fit model and
      95% confidence intervals were estimated by a Monte Carlo procedure with a
      bootstrap technique. RESULTS: The success rate of residents was 80% after 32
      procedures (95% confidence interval of 0.59 to 1.00). The pooled success rate of
      the staff anesthesiologists was 0.73 (mean) with a standard deviation of 0.45,
      which was not statistically different from the success rate of the residents.
      CONCLUSION: High success rates in performing caudal anesthesia in pediatric
      patients can be acquired after a limited number of cases. Success rates of
      residents learning this procedure are comparable to the results of staff
      anesthesiologists.

PMID- 10925936
TI  - The bilateral effect of stellate ganglion block on the facial skin blood flow.
AB  - BACKGROUND AND OBJECTIVES: It is our hypothesis that stellate ganglion block
      increases regional blood flow on the blocked side, but does not change cardiac
      output, suggesting that the corresponding regional blood flow on the
      contralateral side may decrease, which would be disadvantageous for patients with
      bilateral sympathetically-maintained pain. The aim of this study is to examine
      the effect of stellate ganglion block on facial skin blood flow. METHODS: Skin
      blood flow on the right and left forehead was measured by a laser blood flowmeter
      before stellate ganglion block and 15 minutes after the block. The block was
      performed for 8 outpatients with acute or chronic pain in the head or neck using
      a 24-gauge needle, 5 mL of 1% mepivacaine, and a paratracheal approach at the C6
      transverse process. Time control without the block was obtained with 9 healthy
      volunteers. RESULTS: All the patients developed the Horner's syndrome on the
      blocked side, but not on the contralateral side. The facial skin blood flow
      increased from 7.5 +/- 1.1 mL/min/100 g to 14.5 +/- 1.4 mL/min/100 g on the
      blocked side (P < .01) and from 8.8 +/- 1.2 mL/min/100 g to 12.8 +/- 1.7
      mL/min/100 g on the contralateral side (P < .05). The healthy volunteers without
      the block showed no significant change (from 10.1 +/- 0.8 mL/min/100 g to 10.3 +/
      0.7 mL/min/100 g). CONCLUSIONS: Our study suggests that stellate ganglion block
      may increase the contralateral regional skin blood flow.

PMID- 10925937
TI  - An in vitro study of dural lesions produced by 25-gauge Quincke and Whitacre
      needles evaluated by scanning electron microscopy.
AB  - BACKGROUND AND OBJECTIVES: A study using scanning electron microscopy showed that
      although the laminas forming the dura mater are concentric and parallel to the
      surface of the medulla, the fiber layers' orientations are different in each sub
      lamina, dispelling the conventional knowledge that all the fibers of the dura are
      arranged in a parallel direction. Thus, this study evaluated the dural lesions
      produced by Whitacre and Quincke spinal needles in the external and internal
      surface of the dura mater of the lower spine area in an attempt to gain more
      insight into the pathophysiology of postdural puncture headaches (PDPH). METHODS:
      The T11-L4 dural membranes from 5 fresh (immediately after extraction of organs
      for transplantation), male patients declared brain dead, ages 23, 46, 48, 55, and
      60 years, were excised by anterior laminectomy. Morphologic orientation of the
      membrane and normal pH were maintained with an apparatus designed for this
      purpose. One hundred punctures (20 on each sample) at 90-degree angles were done
      with a new needle each time, 50 with 25-gauge Whitacre and 50 with 25-gauge
      Quincke needles. Half of the punctures with the Quincke needles were done with
      the bevel in parallel direction to the axis of the spinal cord, and the rest with
      the bevel perpendicular to it. Fixation in solutions of 2.5% glutaraldehyde
      phosphate buffer, followed by dehydration with acetone, was done 15 minutes after
      the punctures. After acetone was removed at ideal conditions of temperature and
      pressure, the specimens were then metallized with carbon followed by gold and
      inspected under a scanning electron microscope. RESULTS: Twenty-five of the
      Whitacre and 23 of the Quincke punctures were found for evaluation. There were no
      differences in the cross-sectional area of the punctures produced by the Whitacre
      or Quincke needles on the dura. The area of the dural lesions produced by 25
      gauge Quincke needles, 15 minutes after they have been withdrawn, was 0.023 mm2
      (confidence interval [CI] 95%, 0.015 to 0.027) in the external aspect (epidural
      surface) and 0.034 mm2 (CI 95%, 0.018 to 0.051) in the internal aspect (arachnoid
      surface) of the dural sac. The area of the lesions produced by the 25-gauge
      Whitacre needles was 0.026 mm2 (CI 95%, 0.019 to 0.032) and 0.030 mm2 (CI 95%,
      0.025 to 0.036) in the external and internal surfaces of the dural sac,
      respectively. There were no significant differences in the cross-sectional areas
      of the punctures produced by the 25-gauge Whitacre or 25-gauge Quincke needles.
      Moreover, with Quincke needles the dural lesions closed in an 88.3% (CI 95%, 86.3
      to 92.4) and 82.7% (CI 95%, 74.1 to 90.9) of their original sizes in the epidural
      and arachnoid surfaces, respectively. With Whitacre needles, the closure occurred
      in an 86.8% (CI 95%, 83.8 to 90.3) and 84.8% (CI 95% 81.7 to 87.3) in the dural
      and arachnoid surfaces, respectively. However, there were differences in the
      morphology of the lesions. The Whitacre needles produced coarse lesions with
      significant destruction in the dura's fibers while the Quincke needles produced a
      'U'-shaped lesion (flap) that mimics the opened lid of a tin can, regardless of
      the tip's direction. CONCLUSIONS: The needles produced lesions in the dura with
      different morphology and characteristics. Lesions with the Quincke needles
      resulted in a clean-cut opening in the dural membrane while the Whitacre needle
      produced a more traumatic opening with tearing and severe disruption of the
      collagen fibers. Thus, we hypothesized that the lower incidence of PDPH seen with
      the Whitacre needles may be explained, in part, by the inflammatory reaction
      produced by the tearing of the collagen fibers after dural penetration. This
      inflammatory reaction may result in a significant edema which may act as a plug
      limiting the leakage of cerebrospinal fluid.

PMID- 10925938
TI  - Tip-holed spinal needle: a new design concept.
AB  - Dura-arachnoid puncture for spinal anesthesia is associated with several
      complications. Postdural puncture headache (PDPH) and needle bending are
      significant among these. The incidence of PDPH has been reduced significantly
      with the advent of pencil-point needles. However, these needles also have their
      limitations, such as obstruction of the delivery port by tissues affecting both
      cerebrospinal fluid flash back and drug delivery. Increasing the size of the
      lateral hole has led to mechanical complications, such as tip bending. A new
      spreading beveled spinal needle tip has been designed to overcome the
      disadvantages of all the currently used spinal needles. To assess the
      feasibility, a 26-gauge Quincke spinal needle (B. Braun, Melsungen, Germany) has
      been modified manually. The new tip-holed design seems to be sound both from
      theoretical and practical point of view. Searching Medline Plus through their
      Internet Web site (www.nlm.nih.com) did not reveal the existence of any such
      spinal needle.

PMID- 10925939
TI  - Nocistatin--a new antinociceptive peptide.

PMID- 10925940
TI  - Computed tomography and the anatomy of celiac plexus block.

PMID- 10925941
TI  - Use of computed tomography for maxillary nerve block in the treatment of
      trigeminal neuralgia.
AB  - BACKGROUND AND OBJECTIVES: Maxillary nerve block has traditionally been performed
      by using external anatomic landmarks. However, the classic approach to the nerve
      may be confounded because of anatomic variability. We describe a technique for
      the block using the suprazygomatic route guided by computed tomography (CT). CASE
      REPORT: A 90-year-old woman had a 30-year history of episodic pain in her right
      maxillary region. We attempted to block the maxillary nerve with classic
      technique, but we could not identify the nerve by eliciting paresthesia. In
      addition, bleeding was noted after repeated attempts. To minimize complications
      and confirm the correct position of the needle tip, we planned the block with a
      suprazygomatic approach using CT guidance. The needle was inserted without
      paresthesia. The CT scan showed the needle tip was placed at the entrance of the
      pterygopalatine fossa and the distribution of contrast medium spread
      appropriately around the pterygopalatine fossa. After confirming the clinical
      effect and lack of complications of the block using the local anesthetic, 0.5 mL
      of 7% phenol was injected. This technique resulted in complete sensory loss in
      the area innervated by the maxillary nerve, and did so without complications.
      CONCLUSIONS: A maxillary nerve block guided by a CT imaging is an alternative to
      classic techniques.

PMID- 10925942
TI  - Computed tomography-guided pudendal nerve block. A new diagnostic approach to
      long-term anoperineal pain: a report of two cases.
AB  - OBJECTIVE: To show the value of computed tomography (CT) in selectively blocking
      the pudendal nerve in patients with long-term anogenital pain of uncertain
      etiology. We report a technique to selectively block the pudendal nerve using CT
      guidance in 2 patients with long-term anogenital pain. CASE REPORT: In 1 patient,
      a competitive cyclist, the diagnosis of pudendal neuralgia was substantiated by
      blocking the nerve under CT. The procedure relieved the pain for approximately 24
      hours. In the other patient, pudendal nerve block produced perineal analgesia but
      no pain relief. Superior hypogastric plexus block relieved the pain significantly
      for about 4 weeks on 2 separate occasions, suggesting sympathetically maintained
      pain. CONCLUSION: The use of CT to guide the procedure allowed precision in
      performing the procedure and in making a differential diagnosis.

PMID- 10925943
TI  - Circumcision supplemented by dorsal penile nerve block with 0.75% ropivacaine: a
      complication.
AB  - BACKGROUND AND OBJECTIVES: Dorsal penile nerve block is a common procedure and
      can provide effective analgesia after penile surgery. Ischemic complications are
      rare and generally result from trauma or inadvertent administration of
      vasoconstrictive solutions. CASE REPORT: We describe a period of temporary
      ischemia of the glans penis occurring 40 minutes after dorsal penile nerve block
      with 0.75% ropivacaine. This was successfully treated with an intravenous
      infusion of iloprost (a PGI2 analogue), and at 43 hours appearances were normal.
      CONCLUSION: Theoretical concerns over the vasoconstrictive properties of
      ropivacaine may be sufficient to avoid its use where the potential for ischemia
      to end organs is present.

PMID- 10925945
TI  - Are there metallic microparticles in every epidural needle?

PMID- 10925944
TI  - Epidural abscess: case report and literature review.
AB  - OBJECTIVE: To report a case of spinal epidural abscess complicating epidural
      analgesia, and to heighten awareness of the condition and the importance of early
      recognition and treatment. CASE REPORT: A 72-year-old woman underwent
      adrenalectomy and groin dissection for recurrent malignant melanoma under
      combined general and epidural anesthesia. On the fourth postoperative day, she
      developed signs of localized infection at the epidural site and a band of reduced
      sensation. Further neurological signs developed before the diagnosis was made by
      magnetic resonance imaging scan. She subsequently underwent emergency laminectomy
      and drainage of epidural abscess. CONCLUSION: Delayed diagnosis allowed the
      development of significant morbidity before neurosurgical intervention and
      antibiotics were instituted.

PMID- 10925946
TI  - Use of contrast before percutaneous neurolytic block.

PMID- 10925947
TI  - Left ventricular contractility is impaired following myocardial infarction in the
      pig and rat: assessment by the end systolic pressure-volume relation using a
      single-beat estimation technique and cine magnetic resonance imaging.
AB  - The end systolic pressure-volume relation (ESPVR) has been shown to be a
      relatively load independent measure of left ventricular (LV) contractility.
      Recently, several single-beat ESPVR computation methods have been developed,
      enabling the quantification of LV contractility without the need to alter
      vascular loading conditions on the heart. Using a single-beat ESPVR method, which
      has been validated previously in humans and assumes that normalized elastance is
      constant between individuals of a species, we studied the effects of myocardial
      infarction on LV contractility in two species, the rat and the pig. In our
      studies, LV pressure was acquired invasively and LV volume determined
      noninvasively with magnetic resonance imaging, at one week postinfarction in pigs
      and at 12 weeks postinfarction in rats. Normalized systolic elastance curves in
      both animal species were not statistically different from that of humans. Also,
      the slope of the ESPVR (Ees) decreased significantly following infarction in both
      species, while the volume-axis intercept (V0) was unaffected. These results
      indicate that a single-beat ESPVR method can be used to measure the inotropic
      response of the heart to myocardial infarction, and that the basis for this
      method (i.e., constant normalized elastance) is applicable to a variety of
      mammalian species.

PMID- 10925948
TI  - Staged growth of optimized arterial model trees.
AB  - There is a marked difference in the structure of the arterial tree between epi-
      and endocardial layers of the human heart. To model these structural variations,
      we developed an extension to the computational method of constrained constructive
      optimization (CCO). Within the framework of CCO, a model tree is represented as a
      dichotomously branching network of straight cylindrical tubes, with flow
      conditions governed by Poiseuille's law. The tree is grown by successively adding
      new terminal segments from randomly selected points within the perfusion volume
      while optimizing the geometric location and topological site of each new
      connection with respect to minimum intravascular volume. The proposed method of
      "staged growth" guides the generation of new terminal sites by means of an
      additional time-dependent boundary condition, thereby inducing a sequence of
      domains of vascular growth within the given perfusion volume. Model trees
      generated in this way are very similar to reality in their visual appearance and
      predict diameter ratios of parent and daughter segments, the distribution of
      symmetry, the transmural distribution of flow, the volume of large arteries, as
      well as the ratio of small arterial volume in subendocardial and subepicardial
      layers in good agreement with experimental data. From this study we conclude that
      the method of CCO combined with staged growth reproduces many characteristics of
      the different arterial branching patterns in the subendocardium and the
      subepicardium, which could not be obtained by applying the principle of minimum
      volume alone.

PMID- 10925949
TI  - Physiological relevance of uniform elastic tube-models to infer descending aortic
      wave reflection: a problem of identifiability.
AB  - A uniform, frictional elastic tube terminating in a pure resistor (model A), was
      compared with a uniform, frictionless elastic tube, terminating in a first-order
      low-pass filter load (model B). The aim was to address an identifiability problem
      in uniqueness of parameter estimates and to evaluate the physiological meaning of
      tube-length estimates obtained from these models applied to the descending aortic
      circulation. Measurements of high descending aortic pressure and flow were taken
      from three anaesthetized, open-chest dogs and used to estimate the model
      parameters. A simultaneous measurement of terminal aortic pressure was used to
      estimate the foot-to-foot pulse wave velocity. A flow-fitting procedure yielded a
      multiplicity of equivalent solutions for the wave transit time across the
      transmission tubes (tau(ai), for model A and tau(bi) for model B,
      i=0,1,2,...,N,...) and the related tube-lengths d(ai) and d(bi), respectively.
      The tube length represents the distance to an effective reflection site
      (effective length) of the descending aortic circulation. Assuming that this
      length should be no longer than the dimensions of the body, the lowest estimates
      (i=0) of wave transit time and tube length (average +/- SE: tau(ao)=85.7+/-10.8
      ms and d(ao)=53.4+/-3.7 cm for model A; tau(bo)=46.6+/-6.7 ms and d(bo)= 29.1+/
      3.5 cm for model B) were identifiable as unique and acceptable solutions. Model A
      located the effective reflection site a few centimeters below the terminal aortic
      region. This location is inconsistent with the use of a pure resistor as a tube's
      terminal load. Further, relatively high estimates of longitudinal frictional
      losses violated the assumption of small losses across the transmission path and
      yielded an unphysiological mean-pressure drop of 7.1+/-2.3 mmHg. The estimates of
      d(bo) provided by model B located the effective reflection site near the origin
      of the renal arteries. The model-predicted pressure wave at this location
      approximated the measured pressure. Thus, model B represents a significant
      improvement over model A as a tool to infer wave travel and reflection in the
      descending aortic circulation.

PMID- 10925950
TI  - An in vitro study of the hinge and near-field forward flow dynamics of the St.
      Jude Medical Regent bileaflet mechanical heart valve.
AB  - The most widely implanted prosthetic valve is the mechanical bileaflet. Recent
      clinical experiences suggest that some designs are more prone to thromboembolic
      episodes than others. This study evaluated the hinge flow and near-field forward
      flow of the new St. Jude Medical Regent bileaflet mechanical heart valve. Laser
      Doppler velocimetry measurements were conducted within the hinge and near-field
      forward flow regions of the Regent valve. These pulsatile flow velocity
      measurements were animated in time to visualize the flow fields throughout the
      cardiac cycle. During forward flow, a recirculation region developed in the
      inflow pocket of the Regent hinge but was subsequently abolished by strong
      backflow during valve closure. Leakage velocities in the hinge region reached
      0.72 m/s and Reynolds shear stresses reached 2,600 dyn/cm2. Velocities in the
      near-field region were highest in the lateral orifice jet, reaching 2.1 m/s.
      Small regions of separated flow were observed adjacent to the hinge region.
      Leaflet motion through the Regent hinge creates a washout pattern which restricts
      the persistence of stagnation zones in its hinge. Based upon the results of these
      studies, the hematological performance of the Regent series should be at least
      equivalent to the performance of the Standard series.

PMID- 10925951
TI  - Directional wall strength in saccular brain aneurysms from polarized light
      microscopy.
AB  - The aneurysm wall, which must withstand arterial blood pressure, is composed of
      layered collagen. Wall strength is related to both collagen fiber strength and
      orientation. When the aneurysm enlarges, the amount and organization of the
      collagen fibers change, potentially increasing the risk of rupture. We studied
      the directional organization and molecular strength of the collagen fibers layer
      by layer across the walls of four aneurysms in order to measure their mechanical
      integrity. The technique incorporates the birefringent properties of collagen,
      enabling us to use linearly polarized light for measuring the orientation of the
      fibers, and the Senarmont compensator to measure the birefringence and thus
      mechanical strength. Intact aneurysms were obtained at autopsy, fixed at
      physiological pressure, sectioned at 4 microm, and stained with 0.05% picrosirius
      red. By combining birefringence and orientation data we estimated tensile
      strength as a function of direction on the aneurysmal wall. The average breaking
      strength of the wall ranged from 0.73 to 1.9 MPa. Comparing the weakest to the
      strongest direction, the breaking strength varied by a factor of up to 2X,
      implying a significant degree of mechanical anisotropy.

PMID- 10925952
TI  - "Artificial lymphatic system": a new approach to reduce interstitial hypertension
      and increase blood flow, pH and pO2 in solid tumors.
AB  - A mechanical drainage system, the "artificial lymphatic system" (ALS), consisting
      of a vacuum source and drain, is evaluated for its ability to aspirate the
      interstitial fluids responsible for the elevated interstitial fluid pressure
      (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured
      before and after aspiration using wick-in-needle (WIN) probes, needle pH and
      oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal
      changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN
      probe and IFP profile data were analyzed using numerical simulation and
      distributed mathematical models, respectively. The model parameter, P(E),
      reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma
      and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration.
      The simulation demonstrated that spatial averaging inherent in WIN measurements
      reduced the calculated magnitude of the model parameter changes. IFP was
      significantly lower (p<0.05), especially in regions surrounding the drain, and
      BFR was significantly higher (p<0.05) following 25 and 45 min of aspiration,
      respectively; pH and pO2 profiles increased following aspiration. The
      experimental and mathematical findings suggest that ALS aspiration may be a
      viable way of reducing IFP and increasing BFR, pO2, and pH and should enhance
      solid tumor chemo and radiation therapy.

PMID- 10925953
TI  - Enhancing the uptake of chemotherapeutic drugs into tumors using an "artificial
      lymphatic system".
AB  - This paper presents findings from uptake studies to evaluate the ability of an
      "artificial lymphatic system" (ALS) to enhance large and small molecular weight
      drug transport into solid tumors and the therapeutic effect of the additional
      drug on their growth. These studies also served to test the effectiveness of an
      implantable multidrain ALS. Walker 256, Neuroblastoma, and Sarcoma dual-tumor
      models were used to evaluate the effect of ALS aspiration on the uptake of 3F8
      monoclonal antibody, and doxorubicin. A tumor shrinkage experiment using Walker
      256 dual tumors was used to evaluate the efficacy of an implantable ALS with
      cyclophosphamide chemotherapy. Drug uptake significantly increased in all
      aspirated tumors; 3F8 uptake was enhanced 37.4% in the Walker and 93.1% in the
      Neuroblastoma tumor lines (p<0.05). Doxorubicin uptake increased 23.2% in Sarcoma
      tumor (p<0.05). The shrinkage study demonstrated that one-drain aspirated tumors
      shrank 90% faster (p<0.01) than control tumors, while three-drain aspirated
      tumors shrank 123% faster than control tumors (p<0.01).

PMID- 10925954
TI  - A computational fluid dynamic model of antigen-antibody surface adsorption on a
      piezoelectric immunosensor.
AB  - A novel computational fluid dynamic model describing the antigen-antibody binding
      on an electrode surface is presented. It was assumed that the adsorption rate of
      the antibody sample is dependent upon the flow field in the vicinity of the
      electrode. Numerical solution of the steady flow in a two-dimensional triangular
      cell using the Navier-Stokes equations was carried out for predicting mass
      adsorption on the surface of the crystal. The relationships between the mass
      adsorbed over the area surface of the electrode, the kinetics of the binding
      process, and the flow field were determined. The effect of the inlet conditions
      (location, velocity magnitude, and direction) on the time constant of the mass
      adsorption process was investigated. It was found that the time constant was
      decreased by moving the inlet near the edge of the crystal or increasing the
      normal to the boundary component of the velocity. These changes may significantly
      reduce the time needed to conduct the test.

PMID- 10925955
TI  - Prototype neural semicircular canal prosthesis using patterned electrical
      stimulation.
AB  - The design of a prototype semicircular canal prosthesis is presented along with
      preliminary results. This device measures angular velocity of the head (+/-500
      degrees/s) using a piezoelectric vibrating gyroscope. With a digital filter this
      velocity is filtered to match the dynamic characteristics of the semicircular
      canals, which are the physiological rotation sensors of the vestibular system.
      This digitally filtered signal is used to modulate the pulse rate of electrical
      stimulation. The pulse rate is varied between 50 and 250 Hz via a sigmoidal
      lookup table relating pulse rate to angular velocity; the steady-state rate is
      150 Hz. A current source utilizes these timing pulses to deliver charge balanced,
      cathodic-first, biphasic, current pulses to the nerves innervating the
      semicircular canal via platinum electrodes. Power is supplied via lithium
      batteries. dc/dc converters are used to generate regulated +/-5 V supplies from
      the batteries. All of the components are contained in a small, lightweight, Nylon
      box measuring roughly 43 mm x 31 mm x 25 mm, which can be mounted on the top of
      an animal's head. This device has been tested in guinea pigs having surgically
      implanted platinum electrodes, and the results show that the prosthesis can
      provide a rotational cue to the nervous system.

PMID- 10925956
TI  - Entrainment of intestinal slow waves with electrical stimulation using
      intraluminal electrodes.
AB  - The aim of this study was to investigate whether the intestinal stimulation would
      be feasible using a less invasive method: intraluminal electrodes. The study was
      performed in nine healthy hound dogs (15-26 kg). Four pairs of electrodes were
      implanted on the serosa of the jejunum at an interval of 5 cm with the most
      proximal pair 35 cm beyond the pylorus. An intestinal fistula was made 20 cm
      beyond the pylorus. Simultaneous recordings of intestinal myoelectrical activity
      were made for 2 h in the fasting state from both intraluminal and serosal
      electrodes. Various pacing parameters were tested. The frequency of the
      intestinal slow wave recorded from the intraluminal electrodes was identical to
      that from the serosal electrodes (18.78+/-0.3 cpm vs 18.75+/-0.3 cpm, r=0.99, p
      <0.001), and so was the percentage of normal 17-22 cycles/ min waves (95.83+/
      3.9% vs 98.16+/-1.33%, r=0.96, p<0.01). A complete entrainment of the intestinal
      slow wave was achieved in every dog with electrical stimulation using
      intraluminal ring electrodes. The effective pacing parameters were pulse width of
      70 ms, amplitude of 4 mA and frequency of 1.1 IF (intrinsic frequency). The time
      required for the entrainment of the intestinal slow wave with intraluminal pacing
      was 25.0+/-2.1 s. The maximum driven frequency was found to be 1.43+/-0.01 IF.
      The results reveal that intraluminal pacing is an effective and efficient method
      for the entrainment of intestinal slow waves. It may become a potential approach
      for the treatment of intestinal motor disorders associated with myoelectrical
      abnormalities.

PMID- 10925957
TI  - Idiopathic recurrent pancreatitis: the ERCP luddites are at the door.

PMID- 10925958
TI  - The problem of gas in irritable bowel syndrome.

PMID- 10925959
TI  - Long-term treatment of Crohn's disease with methotrexate, or, why's a nice drug
      like you still a wannabe in the treatment of inflammatory bowel disease?

PMID- 10925960
TI  - Doubling time of flat and polypoid colorectal neoplasms: defining the adenoma
      carcinoma sequence.

PMID- 10925961
TI  - Putting rectal 5-aminosalicylic acid in its place: the role in distal ulcerative
      colitis.
AB  - Oral aminosalicylates such as sulfasalazine and mesalamine are widely prescribed
      for the treatment of mild or moderately active distal ulcerative colitis.
      However, a critical review of the literature demonstrates that rectal 5
      aminosalicylic acid (5-ASA) is the optimal therapy for this disease. Meta
      analyses of published trials show that rectally delivered 5-ASA is superior to
      placebo and to conventional rectal corticosteroids in inducing remission of
      distal ulcerative colitis, whereas the combination of rectal 5-ASA with a rectal
      corticosteroid or oral aminosalicylate is superior to rectal 5-ASA alone. For
      maintaining remission of distal ulcerative colitis, rectal 5-ASA is significantly
      better than placebo and at least as effective as oral 5-ASA. The dosage forms
      available for rectal delivery include suppositories, foams, and liquid enemas,
      and selection among these preparations should be guided by the proximal extent of
      disease and patient preference. The efficacy of rectal 5-ASA is complemented by
      its low rate of reported adverse effects, which may reflect its reduced potential
      for systemic absorption. This review summarizes the evidence supporting the role
      of rectal 5-ASA as a first-line therapy for mild or moderately active distal
      ulcerative colitis, and offers guidelines for its use.

PMID- 10925962
TI  - Placebos: a review of the placebo response.
AB  - Placebos have been a component of healing since the beginning. Whether
      consciously or unconsciously given, they are largely responsible for the success
      of medicine before randomized trials. Yet, even in this era of "evidence-based
      medicine," placebos remain enigmatic, and elicit mixed attitudes from divers
      disciplines. However, our ignorance is not total. There are a few facts to cling
      to and old myths to dispel. The effect of placebos seems to encompass such
      disparate elements as anxiety, conditioning, expectation, the healer's persona,
      and the attachment of meaning to illness. Placebos may obscure as well as
      illuminate the truth about treatment effectiveness. Moreover, it is easy to
      confuse their effect with the natural progression of the disease being treated.
      Those engaged in treatment trials must recognize and manage the reality of
      placebos rather than attempt to eliminate or disparage them. Factors that might
      influence the placebo effect such as age, gender, and social circumstances need
      prospective study. Meanwhile doctors, through honest and compassionate
      interactions with patients, should strive to maximize their treatments' benefits.
      This implies confident reassurance and the provision of some meaning to the
      person's symptoms.

PMID- 10925963
TI  - Bone marrow micrometastases and gastrointestinal cancer detection and
      significance.
AB  - Accurate staging of cancer is important, as the presence or absence of systemic
      spread determines treatment. The sensitivity of current imaging and biochemical
      techniques is suboptimal for the detection of minimal residual disease and latent
      metastases. This results in understaging and potential undertreatment. To improve
      detection of disseminated epithelial malignancy, immunohistochemical and
      molecular methods have been employed that search for epithelial cell-specific
      proteins in nonepithelial tissue. Bone marrow is mesenchymal tissue (that does
      not normally express epithelial cell components) and represents an accessible
      window for detection of micrometastatic carcinoma cells. Detection methods for
      epithelial cell components (cytokeratins, epithelial membrane antigen,
      carcinoembryonic antigen) include immunohistochemistry, flow cytometry, reverse
      transcriptase polymerase chain reaction (rt-PCR), and enzyme linked immunoassay
      (ELISA). Micrometastatic cells in bone marrow are viable, capable of
      proliferation, resistant to immune attack, and insensitive to s-phase
      chemotherapeutic agents. Patients with carcinomas of the lung, breast, prostate,
      or gastrointestinal tract and in whom bone marrow micrometastases are detected
      have a foreshortened interval to recurrence and impaired survival. Detection of
      micrometastases deserves serious consideration in treatment protocols, and
      standardization of methods is now required.

PMID- 10925964
TI  - The potential role of the esophageal pre-epithelial barrier components in the
      maintenance of integrity of the esophageal mucosa in patients with endoscopically
      negative gastroesophageal reflux disease.
AB  - OBJECTIVE: Patients with gastroesophageal reflux disease (GERD) accompanied by
      erosive reflux esophagitis (RE) exhibit an impairment within the esophageal pre
      epithelial barrier protective components that may facilitate the development
      and/or progression of the mucosal injury. Little is known, however, whether such
      impairment is a general phenomenon affecting all patients with GERD or whether
      this is a characteristic feature only of patients with erosive RE. We therefore
      studied the rate of secretion of esophageal inorganic and organic protective
      factors in patients with endoscopically negative [E (-)] GERD and compared these
      results with the corresponding values in asymptomatic volunteers (CTRL). METHODS:
      The study was conducted on 33 white asymptomatic volunteers and 10 white patients
      with a long history of GERD confirmed by 24-h pH monitoring and a grossly
      negative upper endoscopy. Esophageal secretion was collected during mucosal
      exposure to NaCl, HCl, HC/pepsin and NaCl using the esophageal perfusion
      catheter. In collected samples all investigated parameters were measured.
      RESULTS: The pH of esophageal secretion and its content of bicarbonate, EGF, and
      PGE2 in patients with E (-) GERD and asymptomatic volunteers were similar.
      Unexpectedly, the rate of esophageal glycoconjugate (predominantly mucin)
      secretion was significantly higher in patients with E (-) GERD than in controls
      during perfusion with HCl (p < 0.05). Furthermore, secretion of protein in
      patients with E (-) GERD was significantly higher than in the control group
      during the mucosal exposure to HCl/Pepsin (p < 0.05). The nonbicarbonate buffer
      secretion during perfusion with HCl and HCl/Pepsin as well as the rate of
      esophageal TGFalpha output during infusion of final saline in patients with E (-)
      GERD were significantly lower than in CTRL group (p < 0.05). CONCLUSIONS: Our
      data indicate that patients with E (-) GERD have an esophageal secretory
      potential, in terms of glycoconjugate and protein, higher than that in
      asymptomatic controls. This phenomenon in patients with E (-) GERD may, by
      enhancing the quantity of the esophageal pre-epithelial barrier, help to prevent
      the development of erosive esophagitis. A significantly lower esophageal
      secretory response in patients with E (-) GERD in terms of nonbicarbonate buffers
      and TGFalpha may facilitate the development of GERD symptoms and histological
      changes of GERD, respectively.

PMID- 10925965
TI  - High power setting argon plasma coagulation for the eradication of Barrett's
      esophagus.
AB  - OBJECTIVE: The term Barrett's esophagus refers to a premalignant condition that
      is characterized by the replacement of the esophageal squamous mucosa by a
      columnar-lined one. Preliminary studies have demonstrated reversal of Barrett's
      mucosa after endoscopic coagulation with different techniques associated with
      acid inhibition. However, most of these studies have shown that residual
      Barrett's glands are found underneath the new squamous epithelium in up to 40% of
      patients. The goal of our study is to verify whether complete restoration of
      Barrett's mucosa can be achieved by the combination of high power setting argon
      plasma coagulation and omeprazole. METHODS: A total of 33 patients (mean age:
      55.2 yr, range: 21-84 yr; 21 men and 12 women) with histologically demonstrated
      Barrett's esophagus (mean length: 4.05 cm, range: 0.5-7 cm) were treated.
      Fourteen cases presented with low-grade dysplasia and one with high-grade
      dysplasia. All of the extent, or until a maximum of 4 cm, of the Barrett's mucosa
      was cauterized in each session using argon beam coagulation at a power setting of
      65-70 W. All patients received 60 mg omeprazole during the treatment period.
      RESULTS: Complete restoration of squamous mucosa was obtained in all 33 cases
      after a mean of 1.96 sessions (range, 1-4). Endoscopic results were
      histologically confirmed. Nineteen (57.5%) patients experienced moderate to
      severe chest pain and odyno-dysphagia lasting for 3-10 days after the procedure.
      Five of these cases experienced high fever and a small volume of pleural
      effusion, and three patients developed esophageal strictures that needed to be
      dilated. Another patient developed pneumomediastinum and subcutaneous emphysema
      without evidences of perforation. After a mean follow-up of 10.6 months there was
      one endoscopic, as well as histological, recurrence of Barrett's mucosa in a
      patient with an ineffective laparoscopic fundoplication. CONCLUSIONS: High power
      setting argon plasma coagulation combined with intensive acid suppression is an
      effective treatment for the total endoscopic ablation of Barrett's esophagus, at
      least in the short term. Long-term follow-up of treated patients in whom
      gastroesophageal reflux is surgically or medically alleviated seems mandatory
      before drawing definitive conclusions about this therapy.

PMID- 10925967
TI  - Long-term follow-up of intestinal metaplasia of the gastric cardia.
AB  - OBJECTIVE: Recent studies have found a relatively high prevalence of gastric
      cardia intestinal metaplasia in individuals presenting for elective upper
      endoscopy. It has been hypothesized that this lesion may be a precursor of
      gastric cardia cancer. Our objective was to identify the incidence of dysplasia
      in patients with gastric cardia intestinal metaplasia. METHODS: Twenty-eight
      patients who had previously been identified with cardia intestinal metaplasia had
      follow-up examinations performed. None of the patients had dysplasia at the time
      of diagnosis. All had an examination at 1 yr, and 20 patients had an examination
      at 3 yr after diagnosis. During follow-up examinations all patients underwent
      vital staining with methylene blue to help identify areas of intestinal
      metaplasia in the cardia. Two to four biopsies were taken from blue-stained
      mucosa. Histological specimens were stained using a combination of hematoxylin
      and eosin with Alcian blue at pH 2.5. RESULTS: There were 27 men and one woman
      with a mean age of 69.8 yr (range, 48-83 yr). The mean length of follow-up was
      2.5 yr (range, 12-46 months). Only one patient was diagnosed with dysplasia (low
      grade) during the study, for an incidence of 1.4% per yr. CONCLUSIONS: The
      prevalence (0%) and incidence (1.4%/yr) of dysplasia in cardia intestinal
      metaplasia are low. Although further studies are needed, screening and
      surveillance for gastric cardia intestinal metaplasia is unlikely to be
      clinically useful for the prevention of gastric cardia cancer.

PMID- 10925966
TI  - Predictors of progression to cancer in Barrett's esophagus: baseline histology
      and flow cytometry identify low- and high-risk patient subsets.
AB  - OBJECTIVE: Barrett's esophagus develops in 5-20% of patients with
      gastroesophageal reflux disease and predisposes to esophageal adenocarcinoma. The
      value of endoscopic biopsy surveillance is questioned because most patients do
      not develop cancer. Furthermore, observer variation in histological diagnosis
      makes validation of surveillance guidelines difficult because varying
      histological interpretations may lead to different estimated rates of
      progression. Thus, objective biomarkers need to be validated for use with
      histology to stratify patients according to their risk for progression to cancer.
      METHODS: We prospectively evaluated patients using a systematic endoscopic biopsy
      protocol with baseline histological and flow cytometric abnormalities as
      predictors and cancer as the outcome. RESULTS: Among patients with negative,
      indefinite, or low-grade dysplasia, those with neither aneuploidy nor increased
      4N fractions had a 0% 5-yr cumulative cancer incidence compared with 28% for
      those with either aneuploidy or increased 4N. Patients with baseline increased
      4N, aneuploidy, and high-grade dysplasia had 5-yr cancer incidences of 56%, 43%,
      and 59%, respectively. Aneuploidy, increased 4N, or HGD were detected at baseline
      in all 35 patients who developed cancer within 5 yr. CONCLUSIONS: A systematic
      baseline endoscopic biopsy protocol using histology and flow cytometry identifies
      subsets of patients with Barrett's esophagus at low and high risk for progression
      to cancer. Patients whose baseline biopsies are negative, indefinite, or low
      grade displasia without increased 4N or aneuploidy may have surveillance deferred
      for up to 5 yr. Patients with cytometric abnormalities merit more frequent
      surveillance, and management of high-grade dysplasia can be individualized.

PMID- 10925968
TI  - Reduced risk of upper gastrointestinal ulcer complications with celecoxib, a
      novel COX-2 inhibitor.
AB  - OBJECTIVE: The aim of this study was to assess the rate of upper gastrointestinal
      (UGI) ulcer complications (bleeding, perforation, or gastric outlet obstruction)
      associated with celecoxib, a specific COX-2 inhibitor, compared with the rate
      associated with nonspecific, nonsteroidal anti-inflammatory drugs (NSAIDs).
      METHODS: A pooled analysis was conducted of 14 multicenter, double-blind,
      randomized, controlled trials (RCTs) and a separate analysis of one long-term
      open label trial that assessed the efficacy and safety of celecoxib for
      symptomatic treatment of arthritis. The RCTs enrolled 11,008 patients with
      osteoarthritis or rheumatoid arthritis treated for 2-24 wk; the long-term open
      label trial enrolled 5,155 patients receiving celecoxib for a maximum of 2 yr. In
      the RCTs, patients were randomly assigned to receive placebo (n = 1,864; 208
      patient-years), celecoxib 25-400 mg b.i.d. (n = 6,376; 1,020 patient-years), or a
      comparator NSAID (n = 2,768; 535 patient-years); NSAIDs were naproxen 500 mg
      b.i.d., diclofenac 50 or 75 mg b.i.d., or ibuprofen 800 mg t.i.d.). In the long
      term, open-label trial, patients received celecoxib 100-400 mg b.i.d. for up to 2
      yr (n = 5,155; 5,002 patient-years). The principal outcome measure of this
      analysis was development of a UGI ulcer complication, which was prospectively
      defined as bleeding, perforation, or gastric outlet obstruction. Ulcer
      complications were assessed and adjudicated by persons blinded to the patient's
      treatment assignment or the study in which the patient participated. RESULTS: In
      the RCTs, UGI ulcer complications occurred in no placebo patients (0 of 1,864
      patients), in 2 of 6,376 celecoxib patients (0.03%), and in 9 of 2,768 patients
      receiving an NSAID (0.33%), corresponding to annual incidences of 0.20% for
      celecoxib (p > 0.05 vs placebo) and 1.68% for NSAIDs (p = 0.002 vs celecoxib and
      placebo). In the long-term open-label trial, nine UGI ulcer complications
      occurred, for an incidence of 0.17% and an annualized incidence of 0.18%.
      CONCLUSIONS: The incidence of UGI ulcer complications associated with celecoxib
      was 8-fold lower than with nonspecific NSAIDs. The incidence of ulcer
      complications observed in celecoxib-treated patients was similar to that in
      patients receiving placebo in the RCTs, and to that in non-NSAID users reported
      in the literature.

PMID- 10925969
TI  - The cost-effectiveness of diagnostic testing strategies for Helicobacter pylori.
AB  - OBJECTIVE: Several noninvasive methods are now available for diagnosing
      Helicobacter pylori infection. Because the prevalence of H. pylori infection is
      variable in patients requiring testing, the optimal testing strategies may vary
      under different conditions. The aim of this study was to evaluate the cost
      effectiveness of competing diagnostic strategies for H. pylori in patients with
      varying H. pylori prevalence. METHODS: A decision analysis was performed
      comparing the costs per number of correct diagnoses achieved by alternative
      sequential testing strategies. Estimates of H. pylori prevalence and test
      characteristics were derived from a systematic review of the MEDLINE
      bibliographic database. Cost estimates were derived from the 2000 Medicare Fee
      Schedule. RESULTS: The enzyme-linked immunosorbent assay (ELISA) test had the
      lowest cost per correct diagnosis at low (30%), intermediate (60%), and high
      (90%) prevalence ($90-$95/correct diagnosis), but its diagnostic accuracy was low
      (80-84%). At low and intermediate prevalence the stool test was more accurate
      (93%), with an average cost of $126-$127 per correct diagnosis. Additional
      confirmatory testing of positive or negative tests increased the diagnostic
      accuracy of the stool test, but had high incremental costs. ELISA testing was
      preferable when prevalence rates were very high (90%), and using a confirmatory
      urea breath test for negative ELISA tests increased the diagnostic accuracy to
      96%, with modest incremental costs. If the cost of the breath test was <$50 or if
      the cost of the stool test is >$82, breath testing became preferable to stool
      testing. If the cost of the stool test fell to <$20, it became preferable to
      ELISA. Similarly, if the cost of the ELISA serology was >$39 then stool testing
      became preferable at all prevalence rates. Fingerstick whole blood tests were not
      cost-effective. CONCLUSIONS: The choice of an initial test for H. pylori
      detection depends on the prevalence of H. pylori infection and the value placed
      on increased diagnostic accuracy. Although ELISA results in the lowest cost
      effectiveness ratios, in patients at low-intermediate pretest probability of
      infection, the stool test provides increased accuracy, with modest incremental
      costs.

PMID- 10925970
TI  - Prospective blinded trial of a fecal antigen test for the detection of
      Helicobacter pylori infection.
AB  - OBJECTIVE: We prospectively studied an FDA-approved stool test for the diagnosis
      of Helicobacter pylori infection based on the detection of antigens shed in
      stool. METHODS: We studied 108 patients undergoing endoscopy. Stool samples were
      collected on the day of the endoscopy and read in a blinded manner by a
      technician who was unaware of the findings of the endoscopy. The results of stool
      testing were compared to those of the rapid urease test (Pyloritek). RESULTS:
      There were 51 patients infected with H. pylori by rapid urease testing and 57 who
      were not. The sensitivity of the stool test was 86% (95% confidence interval: 77
      96%), the specificity was 91% (81-97%), with a positive predictive value of 89%
      (77-96%) and a negative predictive value of 88% (81-97%). The likelihood ratio
      for a positive test was 10.18 and the likelihood ratio for a negative test was
      0.11. CONCLUSIONS: The stool test was sensitive and specific for the detection of
      H. pylori in a U.S. population.

PMID- 10925971
TI  - Idiopathic recurrent pancreatitis: long-term results after ERCP, endoscopic
      sphincterotomy, or ursodeoxycholic acid treatment.
AB  - OBJECTIVE: In about 30% of cases, the etiology of acute recurrent pancreatitis
      remains unexplained, and the term "idiopathic" is currently used to define such
      disease. We aimed to evaluate the long-term outcome of patients with idiopathic
      recurrent pancreatitis who underwent endoscopic cholangiopancreatography (ERCP)
      followed by either endoscopic biliary (and seldom pancreatic) sphincterotomy or
      ursodeoxycholic acid (UDCA) treatment, in a prospective follow-up study. METHODS:
      A total of 40 consecutive patients with intact gallbladder entered the study
      protocol after a 24-month observation period during which at least two episodes
      of pancreatitis occurred. All patients underwent diagnostic ERCP, followed by
      biliary or minor papilla sphincterotomy in cases of documented or suspected bile
      duct microlithiasis and sludge, type 2 sphincter of Oddi dysfunction, or pancreas
      divisum with dilated dorsal duct. Patients with no definite anatomical or
      functional abnormalities received long-term treatment with UDCA. After biliary
      sphincterotomy, patients with further episodes of pancreatitis underwent main
      pancreatic duct stenting followed by pancreatic sphincterotomy if the stent had
      proved to be effective. RESULTS: ERCP found an underlying cause of pancreatitis
      in 70% of cases. Patients were followed-up for a period ranging from 27 to 73
      months. Effective therapeutic ERCP or UDCA oral treatment proved that occult bile
      stone disease and type 2 or 3 sphincter of Oddi dysfunction (biliary or
      pancreatic segment) had been etiological factors in 35 of the 40 cases (87.5%)
      After therapeutic ERCP or UDCA, only three patients still continued to have
      episodes of pancreatitis. CONCLUSIONS: Diagnostic and therapeutic ERCP and UDCA
      were effective in 92.5% of our cases, over a long follow-up, indicating that the
      term "idiopathic" was justified only in a few patients with acute recurrent
      pancreatitis.

PMID- 10925972
TI  - The clinical and economic impact of alternative staging strategies for
      adenocarcinoma of the pancreas.
AB  - OBJECTIVE: Several innovative imaging modalities, including endoscopic
      ultrasound, have increased the number of available preoperative staging methods
      in patients with adenocarcinoma of the pancreas. Our goal was to estimate the
      clinical outcomes and cost-effectiveness of alternative staging strategies for
      pancreatic adenocarcinoma. METHODS: Decision analysis was used to simulate
      alternative staging strategies. Cost inputs were based on Medicare
      reimbursements; clinical inputs were obtained from the available literature.
      Model endpoints of interest were cost per curative resection and appropriateness
      of treatment allocation based on pathological stage. RESULTS: Endoscopic
      ultrasound followed by laparoscopy yielded the lowest cost per curative resection
      ($37,600) and minimized the number of unnecessary surgical explorations (5.4 per
      100 patients staged). Requiring angiographic confirmation when endoscopic
      ultrasound demonstrated an unresectable tumor yielded an intermediate cost
      effectiveness ratio and virtually eliminated the risk of overstaging. Laparoscopy
      alone maximized the resection rate, but each additional resection would cost
      approximately $2 million relative to a strategy employing both endoscopic
      ultrasound and angiography. CONCLUSIONS: Staging strategies incorporating
      endoscopic ultrasound may improve treatment allocation and are cost-effective
      relative to angiography-based strategies. A staging protocol that does not
      incorporate an imaging modality to detect vascular invasion dramatically
      increases the cost per additional curative resection compared with more
      comprehensive staging protocols.

PMID- 10925973
TI  - Hemorrhoid banding using videoendoscopic anoscopy and a single-handed ligator: an
      effective, inexpensive alternative to endoscopic band ligation.
AB  - OBJECTIVE: We evaluated a technique of hemorrhoid banding using videoscopic
      anoscopy and a single-handed ligator that offers substantial cost savings over
      endoscope-mounted devices. METHODS: Patients with rectal bleeding from grade
      II/III hemorrhoids had videoscopic anoscopy, which provided a magnified view,
      allowing accurate localization of the hemorrhoids and the dentate line before
      banding, and a photographic record, if required. Banding was performed using a
      suction ligator that could be operated by one hand, allowing the other to control
      the anoscope. RESULTS: Of 39 patients with second- and third-degree hemorrhoids,
      34 (87%) had no further bleeding after a single banding session and a further
      three had no recurrence after a second session. The only complications were pain
      (one patient) and infection (one patient). CONCLUSIONS: This method is convenient
      and effective, costing per procedure less than one-tenth of endoscope-mounted
      band ligators. We recommend its use in preference if magnified views and a
      photographic record are required. However, its cost and complexity, compared with
      traditional hemorrhoid banding, may mean that the latter is preferred in the
      office setting.

PMID- 10925974
TI  - Effect and outcomes of the ASGE guidelines on the periendoscopic management of
      patients who take anticoagulants.
AB  - OBJECTIVE: In December 1997, the American Society of Gastrointestinal Endoscopy
      (ASGE) issued guidelines regarding periendoscopic management of patients who take
      anticoagulants. They recommended that physicians substitute heparin for warfarin
      in their patients who have highly thrombotic conditions (e.g., a mechanical valve
      in the mitral position), and who will undergo high-risk procedures (e.g.,
      polypectomy). The purpose of this study was to assess whether patient outcomes
      and anticoagulant management changed after the publication of the 1997
      guidelines. METHODS: We collected utilization data on all 104 patients at the
      Veterans Affairs Palo Alto Health Care System who were taking chronic warfarin
      therapy and who underwent endoscopic procedures during the study period (1996
      1999). These patients underwent 99 colonoscopies, 63 upper endoscopies, and nine
      endoscopic retrograde cholangiopancreatographies. According to the ASGE
      guidelines, 18 of these patients had highly thrombotic conditions, whereas the
      remaining 86 patients had relatively low thrombotic conditions. We calculated
      their costs for intravenous or subcutaneous heparin therapy from the perspective
      of society. We followed-up all patients for 3 months, to determine the incidence
      of thrombotic and hemorrhagic outcomes. RESULTS: No patient suffered a
      thromboembolism or a hemorrhage; thus, the adverse-event rate (95% confidence
      interval) was 0% (0-3%). As recommended by the ASGE guidelines, all five (100%)
      patients who had highly thrombotic conditions had heparin substituted for
      warfarin before undergoing high-risk procedures. This strategy was also followed
      in 44 (27%) of the 166 procedures in other patients: 16 high-risk procedures in
      low-risk patients, and 28 low-risk procedures (in 20 low-thrombotic patients and
      in eight high-thrombotic patients). There was no significant difference between
      the management of any patients before and after the publication of the
      guidelines. The average cost per course of heparin therapy (typically 2 days
      intravenous heparin preprocedure, and 3 days heparin administered subcutaneously
      postendoscopy) was $1684. In all, 44 (90%) of 49 courses of heparin substituted
      for warfarin therapy were not recommended by the guidelines. CONCLUSIONS:
      Patients treated by the ASGE guidelines had the same 0% rate of thrombosis as
      patients who received periendoscopic heparin outside of the guidelines. Following
      the ASGE guidelines in all patients would have reduced the use of heparin therapy
      by 90%, for a net savings of $74,100.

PMID- 10925975
TI  - Role of flexible endoscopy in the evaluation of possible esophageal trauma after
      penetrating injuries.
AB  - OBJECTIVE: In urban medical centers, penetrating injuries of the chest, neck, and
      head are frequently encountered due to the use of firearms and sharp weapons.
      Successful management of esophageal injury requires a high index of suspicion and
      prompt diagnosis. The role of flexible endoscopy, a readily available modality,
      has not been studied extensively in the management of potential esophageal
      injuries due to trauma. METHODS: A retrospective chart review of 55 patients who
      underwent emergent flexible endoscopy for the evaluation of suspected penetrating
      esophageal injuries was performed to determine if endoscopy was safe and if it
      yielded information that altered patient management. RESULTS: Flexible endoscopy
      was performed safely in all patients. It yielded a sensitivity of 100%,
      specificity of 92.4%, a negative predictive value of 100%, and a positive
      predictive value of 33.3% for detecting an esophageal injury. Although positive
      findings (prevalence, 3.6%) are infrequent, no esophageal injuries were missed.
      Endoscopy altered patient management in 38 (69.1%) patients. CONCLUSIONS:
      Emergent flexible endoscopic examination of the esophagus is a safe and useful
      diagnostic tool in the early evaluation of penetrating injuries. Flexible
      endoscopy resulted in four negative surgical explorations, which was deemed
      acceptable by the Trauma Service, as the consequences of a missed esophageal
      injury is likely to be devastating.

PMID- 10925976
TI  - Methotrexate in Crohn's disease: long-term efficacy and toxicity.
AB  - OBJECTIVE: A 16-wk, placebo-controlled trial has recently shown weekly low-dose
      methotrexate to be an effective treatment for patients with chronically active
      Crohn's disease. The long-term efficacy and safety of this antimetabolite drug,
      however, are not yet well established and are assessed in this study. METHODS: A
      total of 49 patients with Crohn's disease who were treated with methotrexate for
      > or =6 months were studied. All patients had been chronically treated with
      steroids; but at the time of initiation, only 27 were still on steroids. Of the
      49 patients, 42 had previously taken azathioprine but were no longer on this drug
      because of intolerance or failure. Clinical remission was defined as a Harvey
      Bradshaw index of <4. RESULTS: In all, 41 patients achieved complete clinical
      remission and were maintained on methotrexate for a median of 18 months (range, 7
      59 months). In these patients the probabilities of relapse were 29%, 41%, and 48%
      at 1, 2, and 3 yr, respectively. A higher rate of relapse was observed in women
      and in patients with ileocolitis. Adverse reactions were recorded in 24 patients,
      requiring discontinuation of methotrexate in five. A liver biopsy was performed
      in 11 patients; a mild steatosis was found in five, a slight dilation of the
      sinusoids in one, a granulomatous hepatitis with a mild portal fibrosis in one,
      and a slight periportal fibrosis in one patient. CONCLUSIONS: This study suggests
      a long-term benefit of maintenance treatment with methotrexate in patients with
      chronically active Crohn's disease, with side effects that are usually only
      moderate.

PMID- 10925977
TI  - Quantitative analysis of bowel gas using plain abdominal radiograph in patients
      with irritable bowel syndrome.
AB  - OBJECTIVE: Ideally, the diagnosis of irritable bowel syndrome (IBS) would be
      achieved using a minimal number of procedures. It is presumed that bowel gas is
      related to IBS, and it is easily visualized by plain abdominal radiograph. In the
      present study, to clarify the relationship between IBS and the quantity of bowel
      gas, the measured bowel gas volume using plain abdominal radiographs was compared
      with the pathology of IBS. METHODS: Plain abdominal radiographs were digitized
      and transmitted to a computer (computed radiography) in 30 IBS patients and 30
      normal controls. The quantity of bowel gas, determined as the pixel value on
      images and standardized by physique, was defined as the gas volume score (GVS).
      Using the mean +/- 2SD of GVS in the control group as the normal score, IBS
      patients were divided into three groups: high, normal, and low. To examine the
      sequential reproducibility of a similar quantity of bowel gas, a second plain
      abdominal radiography was performed about 2 months later, and the GVS were
      compared. The colonic transit time was determined using radiopaque markers.
      RESULTS: There was a strong correlation between the quantities of bowel gas
      measured by two independent gastroenterologists. The mean GVS of IBS patients was
      significantly higher than that in the control group (p < 0.001). The sequential
      reproducibility was recognized in all 10 IBS patients. There was no significance
      between colonic transit time and GVS, nor between symptoms and GVS. CONCLUSIONS:
      Abdominal gas was analyzed objectively by using GVS, and GVS was considered to
      represent a useful tool for the diagnosis of IBS.

PMID- 10925978
TI  - Importance of gluten in the induction of endocrine autoantibodies and organ
      dysfunction in adolescent celiac patients.
AB  - OBJECTIVE: It is well known that a high number of celiac patients may develop
      autoantibodies against endocrine glands, but it has not yet been clarified if
      this increased autoimmune response and the impaired organ function that can
      develop may be related to the presence or absence of gluten in the diet. The aim
      of the present study was to evaluate the effect of gluten on the autoimmunity and
      function of the endocrine glands in adolescent celiac patients. METHODS: To
      clarify this aspect we investigated 44 patients (28 females), aged 11-20 yr
      (15.21+/-2.7 yr): 25 (mean age, 15.1+/-2.2 yr) on a gluten-free diet (treated
      patients) and 19 (mean age 15.4+/-2.9 yr) with a diet containing gluten
      (untreated patients). Forty adolescent subjects, aged 14-19 yr (mean age, 14.9+/
      2.7 yr), of whom 20 were females, were studied as controls. Antibodies against
      the thyroid, adrenal, and pancreas were evaluated. Thyroid-stimulating hormone
      FT3, FT4, T3, T4, dehydroepiandrosterone sulphate, 17-OH progesterone, and
      cortisol, analyzed basally and 60 min after intravenous ACTH stimulation, were
      assayed to evaluate thyroid and adrenal function. The fasting glycemia level was
      used to evaluate the endocrine pancreas function. An ultrasonogram of the thyroid
      gland was performed on all patients. HLA class II typing for DR3 and DQB1 was
      performed in 32 of 44 patients. RESULTS: Seven of 44 (15.9%) patients were
      positive for antibodies against peroxidase. Six of 44 (13.6%) were positive for
      antibodies against thyreoglobulin and four of them also showed positive
      antibodies against peroxidase. Therefore, in nine of 44 at least one antibody
      directed against thyroid tissue was positive. Seven of 44 (15.9%) were positive
      for antibodies against islet cell, one of 44 (2.3%) positive for antibodies
      against glutamic acid decarboxilase, one of 44 (2.3%) positive for antibodies
      against insulin, and none for antibodies against islet cell- 512bdc. In 15 of 44
      (34%) at least one antibody against an endocrine tissue was positive. The
      genotype DR3 was found in 21 of 32 (65.6%) celiac patients (10 in the untreated
      and 11 in the treated group, respectively) and the genotype DQB1*02 (DQ2) was
      found in 30 of 32 (93.8%) patients (16 in the treated and 14 in the untreated
      group, respectively). DHA-S values were significantly lower in the untreated
      (30.5+/-28.5 microg/dl) than in the treated group (61.3+/-59.4 microg/dl, p <
      0.05), and both showing significantly (p < 0.01) lower levels with respect to the
      controls (161+/-52 microg/dl). One patient showed diabetes, another one clinical
      hypothyroidism (thyroid-stimulating hormone > 6), and two patients showed
      preclinical hypothyroidism. Interestingly, at least one antibody was positive in
      10 of 19 untreated patients (52.6%) but only in five of 25 treated patients
      (20%), with a significantly different distribution (p < 0.001) between the two
      groups and without differences in the HLA genotype. The ultrasonographic
      evaluation of the thyroid resulted in a pathological score in six patients of the
      44 examined (13.6%), suggesting the presence of thyropathy. CONCLUSIONS: The main
      results of this study are the high incidence of thyroid and pancreatic
      antibodies, and the possible role of gluten in the induction of the antibodies as
      well as, in few cases, the consequent organ dysfunction.

PMID- 10925979
TI  - Long-term use of mesalamine (Rowasa) suppositories in remission maintenance of
      ulcerative proctitis.
AB  - OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a
      single nightly 500-mg Rowasa (mesalamine) suppository as maintenance therapy for
      patients with ulcerative proctitis in remission. METHODS: In this 24-month,
      multicenter, double-blind trial, 65 patients with ulcerative proctitis in
      clinical and endoscopic remission were randomized to receive either a single
      nightly 500-mg rectal mesalamine (Rowasa) suppository or matching placebo as sole
      therapy. Efficacy was assessed by time to relapse (defined as rectal bleeding or
      increase in stool frequency for > or =1 wk and active inflammation upon
      endoscopy). RESULTS: Mean time to relapse was 453.4 days for mesalamine-treated
      patients and 158.0 days for placebo-treated patients. Survival analysis
      demonstrated that time to relapse was significantly greater for mesalamine
      treated patients than for placebo-treated patients (p < 0.001). In addition, at
      both 12 and 24 months, the proportion of placebo-treated patients (86% at 12
      months and 89% at 24 months) who relapsed was significantly (p < or = 0.001)
      greater than mesalamine-treated patients (32% and 46%, respectively). No
      statistically significant differences occurred between treatment groups in the
      reporting of any particular adverse event or the number of patients reporting
      adverse events. CONCLUSIONS: The results demonstrate that mesalamine
      suppositories are efficacious, well tolerated, and safe for the long-term
      maintenance of remission of ulcerative proctitis.

PMID- 10925980
TI  - Psychological disorders in patients with evacuation disorders and constipation in
      a tertiary practice.
AB  - OBJECTIVE: We aimed to evaluate the prevalence of psychological impairment in
      patients with rectal evacuation disorders and the influence of psychological
      disorder on the early outcome of behavioral treatment. METHODS: We
      retrospectively reviewed the medical records of patients with rectal evacuation
      disorders referred for biofeedback retraining at a tertiary referral center. The
      psychological disorder was classified using the DSM IV criteria. Outcome of
      biofeedback treatment of evacuation at 2 wk was based on symptoms or on the
      ability to spontaneously expel a balloon placed in the rectum. Improvements in
      the groups without versus with a psychological disorder or an eating disorder
      were compared by Fisher's exact test. RESULTS: In the 60 patients (55 women; 5
      men; mean age, 38 yr), psychological disorders were identified in 39 (65%); also
      noted were eating disorder (n = 5), rumination syndrome (n = 3), pain disorder (n
      = 6), anxiety-depression (n = 10), a combination of depression and pain disorder
      (n = 3), and a combination of eating disorder with anxiety-depression and pain
      disorder (n = 12). There was an association between psychological status and
      outcome at 2 wk of behavioral treatment for evacuation disorder (p = 0.03). The
      coexistence of eating disorder and psychological disorder resulted in an
      unfavorable outcome (p = 0.02), compared with those without psychological
      disorder. CONCLUSION: Psychological impairment was identified in 65% of the
      patients with evacuation disorder and constipation in a tertiary care practice,
      and has a significant negative impact on the outcome of behavioral treatment.
      These data reinforce the importance of a multidisciplinary approach in the
      management of these patients.

PMID- 10925981
TI  - Colonic motility after surgery for Hirschsprung's disease.
AB  - OBJECTIVE: Years after surgery for Hirschsprung's disease, many children continue
      to suffer from fecal incontinence or constipation. The purpose of the present
      investigation was to define the physiology underlying the persistent symptoms in
      children after surgery for Hirschsprung's disease, and to determine the outcome
      of interventions based on the results of the motility testing. METHODS: We
      studied 46 symptomatic patients (5.5+/-3.3 yr old, 35 male) >10 months after
      surgery for Hirschsprung's disease. We performed a colonic manometry with a
      catheter placed with the tip in the proximal colon. We used a structured
      questionnaire and phone interview to follow up the patients an average of 34
      months after the manometry. RESULTS: We identified four motility patterns: 1)
      high-amplitude propagating contractions (HAPCs) migrating through the neorectum
      to the anal sphincter, associated with fecal soiling (n = 18); 2) normal colonic
      manometry associated with fear of defecation and retentive posturing (n = 9); 3)
      absence of HAPCs or persistent simultaneous contractions over two or more
      recording sites (n = 15), associated with constipation (n = 13); and 4) normal
      colonic motility and a hypertensive internal anal sphincter (>80 mm Hg) (n = 4).
      We based treatment on results of the motility studies. There was improvement in
      global health (mean score, 3.9+/-1.1 vs 2.8+/-1.3 at the time of initial
      evaluation, p < 0.001) and emotional health (3.8+/-1.1 vs 2.6+/-1.1, p < 0.0001).
      Improvement in the number of bowel movements occurred in 72% of children.
      Resolution or decreased abdominal pain was reported in 80%. CONCLUSIONS: Colonic
      manometry clarifies the pathophysiology and directs treatment in symptomatic
      children after surgery for Hirschsprung's disease.

PMID- 10925982
TI  - TT virus infection during chronic hepatitis C.
AB  - OBJECTIVE: The pathogenic role of TT virus (TTV) is not well known, especially
      during chronic hepatitis C virus (HCV) infection. We retrospectively investigated
      the presence of TTV DNA in the plasma of patients with chronic HCV infection and
      compared the characteristics of TTV-DNA-positive and -negative groups. METHODS:
      Between November 1996 and November 1998, 234 patients were included. Inclusion
      criteria were persistently elevated serum alanine aminotransferase (ALT) levels,
      anti-HCV and HCV-RNA positivity, and seronegativity for hepatitis B virus and
      human immunodeficiency virus markers. TTV DNA was amplified in nested polymerase
      chain reaction with TTV-specific primers, and products were analyzed by agarose
      gel electrophoresis. Data were analyzed using the chi2, Fisher's exact test, or
      Mann-Whitney test, as appropriate. RESULTS: TTV DNA was detected in 19 (8.1%; 95%
      confidence interval: 4.6-11.6%) patients. TTV-DNA-positive and TTV-DNA-negative
      patients did not differ statistically for age, gender ratio, source of HCV
      infection, HCV disease duration, biological parameters, histological grade, HCV
      RNA load, or HCV genotype. Although nonsignificant (p = 0.21), there was a trend
      for a higher prevalence of TTV DNA in patients with an unknown cause of HCV
      infection (4/22, 18.2%) than in intravenous drug users (4/84; 4.8%), in those
      exposed to potential risk factors (4/49; 8.2%), or in those having received blood
      transfusion (7/79; 8.9%). CONCLUSIONS: Because the rates of HCV replication and
      the severity of liver lesions in TTV-DNA-negative and -positive patients were
      similar, the hepatic pathogenicity of TTV in chronic hepatitis C patients is
      questionable.

PMID- 10925983
TI  - Patients with ascites have higher variceal pressure and wall tension than
      patients without ascites.
AB  - OBJECTIVE: It has been suggested that ascites is a risk factor for variceal
      bleeding. Recently, it has been demonstrated that total paracentesis decreases
      variceal pressure. However, no data are available showing the basal variceal
      pressure in patients with and without ascites. METHODS: We studied 76 cirrhotic
      patients, 49 with and 27 without ascites. Variceal pressure was measured by
      direct puncture. Variceal size, variceal pressure gradient, and variceal wall
      tension were also obtained. RESULTS: No demographic differences were observed
      between the groups. Child score was higher (9.7+/-1.5 vs 7.8+/-2.1, p < 0.001)
      and serum albumin lower (2.6+/-0.6 vs 3.0+/-0.7 mg %, p < 0.02) in ascitic than
      in nonascitic patients, respectively. Variceal pressure and variceal pressure
      gradient were significantly higher in patients with ascites than in those without
      ascites (25.0+/-6 vs 20.4+/-4.6 mm Hg, p < 0.001 and 18.75+/-4.7 vs 13.70+/-4.1
      mm Hg, p < 0.0001, respectively). The variceal wall tension was significantly
      higher in patients with ascites (71.0+/-25.1 mm Hg/mm) than in those without
      ascites (55.1+/-22.1 mm Hg/mm, p < 0.03). No relationship was observed between
      variceal pressure gradient and liver function. Ascites patients included in Child
      Pugh grade A+B presented a similar variceal pressure to Child C patients (18.5+/
      4.2 vs 19.3+/-5.7 mm Hg, respectively, p = ns). In addition, no relationship was
      observed between variceal pressure gradient and etiology of cirrhosis.
      CONCLUSION: Our results demonstrate that patients with ascites have significantly
      higher variceal pressure and wall tension than patients without ascites. These
      results suggest that patients with ascites may be at risk for variceal bleeding.

PMID- 10925984
TI  - Clinical implications of TT virus superinfection in patients with chronic
      hepatitis C.
AB  - OBJECTIVE: TT virus (TTV) has been identified as a candidate agent of non-A-E
      hepatitis virus. We investigated superinfection of TTV in patients with chronic
      hepatitis C and studied the susceptibility to interferon (IFN) treatment and its
      association with liver disease caused by hepatitis C virus (HCV). METHODS: TTV
      DNA was examined using the seminested polymerase chain reaction (PCR), and its
      virus level was measured by the real-time fluorometric PCR. RESULTS: TTV DNA was
      detected in 20 of 102 (19.6%) patients examined. There was no significant
      difference in the alanine aminotransferase (ALT) level between patients with or
      without TTV DNA. Quantitative analysis of HCV RNA and TTV DNA revealed no
      correlation between virus levels in HCV/TTV-coinfected patients. Both TTV and HCV
      were sensitive to IFN therapy. Complete response to IFN with a sustained loss of
      viremia for 24 wk after completion of IFN treatment was found in 11 of 20 (55%)
      patients with respect to TTV DNA and in five of 20 (25%) patients with respect to
      HCV RNA. The mean pretreatment HCV RNA level was significantly lower in the
      complete-response cases than in the no-response cases, but there was no
      significant difference in the pretreatment TTV DNA levels between them. ALT
      normalization resulting from IFN therapy was not attributable to the eradication
      of TTV DNA but was attributable to that of HCV RNA. Superinfection by TTV did not
      influence the effect of IFN against HCV. No specific TTV genotype correlating
      with IFN sensitivity was found. CONCLUSIONS: These results suggest that TTV
      infection stands independent of HCV infection, with no influence on liver injury
      as a result of HCV infection.

PMID- 10925985
TI  - Mutations in interferon sensitivity-determining region of hepatitis C virus: its
      relation to change in viral load.
AB  - OBJECTIVE: Interferon sensitivity-determining region (ISDR) in nonstructural
      region 5A of hepatitis C virus (HCV) genotype-1b has been reported to be
      associated with viral load. Viral load is usually small in the patients with
      mutant type (four or more amino acid substitutions, compared with HCV-J) and
      large in those with wild (identical to HCV-J) or intermediate type (from one to
      three amino acid substitutions). A possible correlation was investigated between
      mutations in ISDR and alterations of viral load during the course of disease.
      METHODS: The sequences of ISDR were determined in eight patients with significant
      changes of viral load and in 11 patients without changes. RESULTS: In two of the
      eight patients with significant alterations of viral load, ISDR sequences changed
      significantly. In one patient whose viral load increased after a course of
      interferon therapy, the number of substitutions, compared with HCV-J, decreased
      from five to zero or one; the type of ISDR converted from mutant type to wild or
      intermediate type. In one patient whose viral load decreased significantly after
      two courses of interferon therapy, the number of substitutions increased from one
      to six; ISDR changed from intermediate type to mutant type. In the remaining six
      patients with changes of viral load and in the other 11 patients without changes,
      the sequences of ISDR did not change significantly. CONCLUSIONS: The mutations in
      ISDR are one of the viral factors involved in the changes in viral load during
      the course of disease, although the majority of other factors involved are still
      unknown.

PMID- 10925986
TI  - Histological evaluation of iron in liver biopsies: relationship to HFE mutations.
AB  - OBJECTIVE: Hepatic iron overload is observed in many forms of chronic liver
      disease. Hereditary hemochromatosis (HH) results in hepatic iron overload and is
      associated with 2 missense mutations in the HFE gene. The aim of this study was
      to define the usefulness of the histological pattern of iron deposition in
      determining the probability of an iron-loaded patient having HFE-related iron
      overload. METHODS: This study assessed liver biopsies containing stainable iron
      from 103 patients with various liver diseases; clinical information included
      hepatic iron concentration and HFE genotype (C282Y, H63D). The biopsies were
      evaluated using a reproducible histological scoring system for iron deposition.
      Three separate components of histological iron deposition were recorded: 1)
      pattern (primarily hepatocellular with a zonal gradient, or reticuloendothelial
      without an obvious zonal gradient), 2) pattern score to denote the extent of iron
      within the acinus, and 3) quantitation grade of iron granules within affected
      hepatocytes. RESULTS: The predominantly hepatocellular pattern (HH pattern) was
      observed in 72 biopsies of which only 42 were from patients homozygous for the
      C282Y mutation, indicating that this pattern alone cannot be used as a surrogate
      marker for HH genotype. The predominantly reticuloendothelial pattern (non-HH
      pattern) was observed in the remaining 31 patients, none of whom was compound
      heterozygous or homozygous for the C282Y mutation (negative predictive value:
      100%). Thus, the non-HH, reticuloendothelial pattern reliably predicts the
      absence of homozygosity for the C282Y mutation. CONCLUSIONS: The use of
      histological evaluation for iron deposition is simple, assists in expanding
      information communicated from histopathologic observations, and may be clinically
      useful in determining the necessity of further evaluation of HFE genotype in
      subjects with histological evidence of hepatic iron overload.

PMID- 10925987
TI  - Retrospective radiographic analysis of nonpedunculated colorectal carcinomas with
      special reference to tumor doubling time and morphological change.
AB  - OBJECTIVE: Our aim was to characterize the development of nonpedunculated
      colorectal carcinomas by retrospective radiographic analysis, with special
      reference to tumor doubling time and morphological change. METHODS: Eleven
      colorectal carcinomas, which were observed for >6 months by barium enema
      examinations, were collected and retrospectively reviewed. There were five early
      and six advanced carcinomas, including submucosally invasive, superficial
      depressed carcinomas. RESULTS: Mean diameter of lesions at initial barium enema
      examination was 13.5 mm (early, 10.4 mm; advanced, 16.0 mm) and that at final
      barium enema examination was 30.9 mm (early, 18.2 mm; advanced, 41.5 mm). Initial
      morphology of the lesions was superficial in three, sessile in seven, and
      semipedunculated in 1. There was no pedunculated lesion. Macroscopic morphology
      of the five early carcinomas was superficial depressed (IIc) in two cases, mostly
      depressed but partly elevated (IIc+IIa) in one case, and superficial elevated
      with a depressed component (IIa+IIc) in two cases; all of the advanced carcinomas
      were of the ulcerated type. Mean doubling time was 6.8 months (early, 9.4 months;
      advanced, 4.7 months). Early carcinomas had significantly longer doubling times
      than advanced carcinomas (p = 0.017, Wilcoxon's text). The lesions with the
      longest doubling times were superficial depressed lesions. CONCLUSIONS: Early
      carcinomas have longer doubling times than advanced carcinomas. Most
      nonpedunculated colorectal carcinomas grow without significant morphological
      changes. Superficial depressed type tumors grow slowly, maintaining their
      macroscopic morphology.

PMID- 10925988
TI  - Cost-utility of one-time colonoscopic screening for colorectal cancer at various
      ages.
AB  - OBJECTIVE: One-time colonoscopy has been recommended as a possible colorectal
      cancer (CRC) screening strategy. Because the incidence of colorectal neoplasia
      increases with age, the effectiveness and cost of this strategy depend on the age
      at which screening occurs. The purpose of this study was to investigate the age
      dependent cost-utility of one-time colonoscopic screening. METHODS: We
      constructed a computer simulation model of the natural history of colorectal
      neoplasia. This model was used to compare the cost-utility of no screening and
      age-based strategies employing one-time colonoscopic screening (age ranges
      evaluated: 45-49, 50-54, 55-59, and 60-64 yr). RESULTS: We determined that one
      time colonoscopic screening in men age <60 yr and in women age <65 yr dominates
      never screening and screening at older ages. For both sexes, one-time
      colonoscopic screening between 50 and 54 yr of age is associated with a marginal
      cost-utility of less than $10,000 per additional quality-adjusted life-year
      compared to screening between 55 and 60 yr of age. One-time colonoscopic
      screening between 45 and 49 yr of age is either dominated (women) or associated
      with a marginal cost-utility of $69,000/per quality-adjusted life-year (men)
      compared to screening between 50 and 54 yr of age. The marginal cost-utility of
      one-time colonoscopic screening is relatively insensitive to plausible changes in
      the cost of colonoscopy, the cost of CRC treatment, the sensitivity of
      colonoscopy for colorectal neoplasia, the utility values representing the
      morbidity associated with the CRC-related health states, and the discount rate.
      CONCLUSIONS: One-time colonoscopic screening between 50 and 54 yr of age is cost
      effective compared to no screening and screening at older ages in both men and
      women. Screening in men between 45 and 49 yr of age may be cost-effective
      compared to screening between 50 and 54 yr of age depending on societal
      willingness to pay.

PMID- 10925989
TI  - Outcome of patients with chronic abdominal pain referred to chronic pain clinic.
AB  - OBJECTIVE: We determined the outcome of patients with chronic abdominal pain of
      unknown etiology referred by gastroenterologists to a chronic pain clinic.
      METHODS: A retrospective chart review of 43 consecutive patients seen by a
      university-based gastroenterology group was referred to our Chronic Pain Clinic
      for evaluation and treatment. Pain character and location, the referring
      diagnosis, and initial Chronic Pain Clinic diagnosis was compared between
      responders and nonresponders. Early and long-term pain relief was scored by
      standard questionnaire. RESULTS: Of the 43 patients with chronic abdominal pain
      of undetermined etiology, 70% reported complete or substantial pain relief by the
      end of chronic pain management. Pain character and location and the referring
      diagnosis were not predictors of pain relief. Long-term pain relief was reported
      by 35% of patients. CONCLUSION: A substantial group of patients with chronic
      abdominal pain of unknown etiology benefited from Chronic Pain Clinic services.

PMID- 10925990
TI  - Suppository mold.

PMID- 10925991
TI  - Scintigraphic long-term follow-up of a patient with metastatic glucagonoma.
AB  - Two years after resection of a pancreatic glucagonoma, scintigraphy with
      111indium-labeled octreotide revealed hepatic metastases in a 48-yr-old man.
      Hepatic metastases were also visualized by CT, whereas an additional lesion in
      the chest was seen only by scintigraphy. A total of 11 follow-up examinations
      over 46 months proved somatostatin receptor scintigraphy to monitor reliably
      somatostatin receptor expression, growth and dissemination of glucagonoma
      metastases, and to indicate therapeutic readjustment if necessary. The survival
      time of the patient is now >75 months, in comparison with a mean survival time of
      59 months reported for metastatic glucagonoma.

PMID- 10925992
TI  - Infected pancreatic pseudocysts with colonic fistula formation successfully
      managed by endoscopic drainage alone: report of two cases.
AB  - Fistulization of pancreatic pseudocysts into surrounding viscera is a well-known
      phenomenon and usually requires surgical management. We report two cases of
      pancreatic pseudocysts that developed spontaneous fistulas to the colon with
      resulting fever and abdominal pain. The patients were managed nonoperatively with
      a combination of endoscopic drainage and antibiotics, and their pseudocysts and
      fistulas resolved. The patients have remained symptom-free for a mean of 14
      months of follow-up.

PMID- 10925993
TI  - Giant fundic polyp complicating attenuated familial adenomatous polyposis.
AB  - This case details the development of a rapidly growing polypoid mass in the
      proximal stomach in a patient with known attenuated familial adenomatous
      polyposis. Surgical resection was required and histology showed hyperplasia with
      extensive areas of dysplastic adenomatous change. This case illustrates that
      patients with the attenuated form of familial adenomatous polyposis are at risk
      for multiple neoplasia distinct from those patients with the classic form of
      familial adenomatous polyposis.

PMID- 10925994
TI  - Lamivudine and hepatitis B: is the bloom already fading?

PMID- 10925995
TI  - Crohn's disease related diarrhea--new answers?

PMID- 10925996
TI  - Is it time for yet another tool to evaluate gastrointestinal bleeding?

PMID- 10925997
TI  - Re: Irwin editorial--cough and GERD.

PMID- 10925998
TI  - Succeeding onset of hepatic, splenic, and renal infarction in polyarteritis
      nodosa.

PMID- 10925999
TI  - Anti-inflammatory effect of rebamipide enema on proctitis type ulcerative
      colitis: a novel therapeutic alternative.

PMID- 10926000
TI  - Are Turkish Helicobacter pylori strains gaining resistance against
      clarithromycin?

PMID- 10926001
TI  - Long-term prognosis of interferon nonresponder children with hepatitis B.

PMID- 10926002
TI  - Herniation of the liver through the rectus muscle presenting as persistent
      abdominal pain.

PMID- 10926003
TI  - Repeated hepatic arterial chemoembolization therapy for management of a patient
      with metastatic carcinoid tumors of the liver.

PMID- 10926004
TI  - Mild pancreatitis in leptospirosis infection.

PMID- 10926005
TI  - Re: A look back--discovery of anesthesia.

PMID- 10926006
TI  - Intestinal metaplasia in an interposed colonic segment in distal esophagus.

PMID- 10926007
TI  - Abnormal activation of transcription factor NF-kappaB involved in steroid
      resistance in chronic inflammatory bowel disease.

PMID- 10926008
TI  - Psoriasis, portal hypertension, and octreotide.

PMID- 10926009
TI  - Cirrhosis associated with heterozygous alpha-1-antitrypsin deficiency preceded by
      a remote history of panniculitis.

PMID- 10926010
TI  - Resveratrol inhibits the growth of Helicobacter pylori in vitro.

PMID- 10926011
TI  - Re: marker of inflammatory bowel disease.

PMID- 10926012
TI  - Appendectomy and the development of ulcerative colitis.

PMID- 10926013
TI  - Peptic ulcer or inflammatory gastric disease?

PMID- 10926014
TI  - Enriching the case history.

PMID- 10926015
TI  - Am I alone?

PMID- 10926016
TI  - Further debate on PubMed Central.

PMID- 10926017
TI  - Reviving patient-oriented research.

PMID- 10926018
TI  - The role of institutional support in protecting human research subjects.
AB  - Institutional review boards (IRBs) and the federal "assurance" procedures play
      critical roles in the current research and regulatory environments for clinical
      research in academic medical centers and other institutions. The author focuses
      on what institutions can and ought to do to create an infrastructure that assures
      the protection of human subjects. Specifically, an institution should (1) create
      an ethics infrastructure in which both IRBs and the function of protecting human
      subjects are respected; (2) assure that adequate resources (space, staff,
      equipment) are available; (3) support IRB members with appropriate recognition
      and time, since their IRB workloads can be heavy; and (4) provide adequate and
      appropriate education for IRB administrators, members, and staff, and for
      investigators and research staff. Academic medical centers should also use their
      expertise in analyzing the current system and developing means of improving it.
      Nevertheless, providing adequate resources for proper research conduct will be
      challenging, given the current financial limitations within academic medical
      centers.

PMID- 10926019
TI  - The primary care specialties working together: a model of success in an academic
      environment.
AB  - In today's environment of decreasing resources and increasing competition among
      clinical delivery systems, survival and ultimate success require
      interdisciplinary cooperation and, if possible, integration. Academic leaders at
      the University of California, Irvine (UCI), have developed a collaborative model
      in which faculty in family medicine, general internal medicine, and general
      pediatrics cooperate extensively in education, research, and patient care.
      Generalist faculty jointly administer and teach both a four-year "doctoring"
      curriculum for medical students and an array of integrated curricula for primary
      care residents, including a communication skills course. Several primary faculty
      jointly developed a collaborative unit for health policy and research, now an
      active locus for multidisciplinary research. Other faculty worked together to
      develop a primary care medical group that serves as a model for interdisciplinary
      practice at UCI. Recently, the university recruited an associate dean for primary
      care who leads the new UCI Primary Care Coalition, reflecting and promoting this
      interspecialty cooperation. This coalition does not represent a step toward a
      generic primary care specialty; UCI's generalist disciplines have preserved their
      individual identities and structures. Yet interdisciplinary collaboration has
      allowed primary care faculty to share educational resources, a research
      infrastructure, and clinical systems, thus avoiding duplicative use of valuable
      resources while maximizing collective negotiating abilities and mutual success.

PMID- 10926020
TI  - A taxonomy of community-based medical education.
AB  - The authors propose a classification of community-based education (CBE) as it is
      implemented all over the world. To create this taxonomy, they used reports in the
      literature of 31 active programs in many locations. A CBE program is an
      instructional program carried out in a community context, outside the academic
      hospital. The authors distinguish between programs that are developed primarily
      to provide services to an underserved community; programs that have a research
      focus; and programs that have as their primary goal the (clinical) training of
      students. These three major types can be subdivided in six minor types, among
      them community development programs, health intervention programs, and simple
      community-exposure programs. The ultimate goal of creating the taxonomy is to
      contribute to the development of a theory of CBE and provide a more systematic
      way to study CBE. In addition, the proposed taxonomy clearly demonstrates the
      various ways in which medical schools, their staffs, and their students can
      become involved with the communities served. CBE is not a unitary concept but a
      set of attempts to contribute to the quality of life in a particular community
      and, at the same time, create conditions for students to acquire hands-on
      understanding of the nature of the problems to be faced in future professional
      practice, and to develop relevant skills. The taxonomy also enables those
      involved in the development of CBE programs in their medical schools to see
      alternative approaches, which will help them choose the approaches that fit their
      particular educational goals. Last, it demonstrates the intricacies involved in
      the implementation of CBE, in particular the complexity of building a learning
      environment that is productive for students and, at the same time, responsive to
      community needs.

PMID- 10926021
TI  - Transforming practice organizations to foster lifelong learning and commitment to
      medical professionalism.
AB  - Practice organizations will increasingly engage in activities that are the
      functional equivalents of continuing medical education. The authors maintain that
      if these activities are properly structured within practice organizations, they
      can become powerful engines of socialization to enhance physicians' lifelong
      learning and commitment to medical professionalism. They propose that this
      promise can be realized if new or reformed practice organizations combine
      education and service delivery and institutionalize processes of individual and
      collective reflection. The resulting "institutions of reflective practice" would
      be ones of collegial, experiential, reflective lifelong learning concerning the
      technical and normative aspects of medical work. They would extend recent methods
      of medical education such as problem-based learning into the practice setting and
      draw on extant methods used in complex organizations to maximize the advantages
      and minimize the disadvantages that practice organizations typically present for
      adult learning. As such, these institutions would balance the potentially
      conflicting organizational needs for, on the one hand, (1) self-direction, risk
      taking, and creativity; (2) specialization; and (3) collegiality; and, on the
      other hand, (4) organizational structure, (5) coordination of division of labor,
      and (6) hierarchy. Overall, this institutionalization of reflective practice
      would enrich practice with education and education with practice, and accomplish
      the ideals of what the authors call "responsive medical professionalism." The
      medical profession would both contribute and be responsive to social values, and
      medical work would be valued intrinsically and as central to practitioners' self
      identity and as a contribution to the public good.

PMID- 10926022
TI  - Improving the protection of human research subjects.

PMID- 10926023
TI  - The need for a community-based, integrated system of care.

PMID- 10926024
TI  - Medicine and the arts. Doc in a Box.

PMID- 10926025
TI  - Latino physician supply in California: sources, locations, and projections.
AB  - PURPOSE: To determine the number of Latino physicians in California, identify the
      schools and countries where they were educated, determine the percentage located
      in Latino areas, and project the supply of Latino physicians to 2020. METHOD:
      From a 1999 list of 74,345 licensed physicians, the authors identified Latino
      U.S. medical graduates (USMGs) by "heavily Hispanic" surnames and Latino
      international medical graduates (IMGs) by country and school of graduation. The
      1999 license addresses of all physicians in Los Angeles County were analyzed
      against 1998 Latino-population data by zip code. A baseline projection of the
      supply of Latino physicians was based on the ten-year (1986 to 1995) average
      annual production of Latino physicians educated in California, out of state, and
      in Latin America. A worst-case projection assumed the continuation of recent
      trends: a 32% decrease in California-educated Latino USMGs, a 19% decrease in out
      of-state Latino USMGs, and a reduction of Latino IMGs to five per year. RESULTS:
      In 1999, 3,578 Latino physicians comprised 4.8% of all Californian physicians. In
      contrast, Latinos made up 30.4% of the state's population. Latino physicians were
      more likely than non-Latinos to have addresses in a heavily Latino zip code. In
      the baseline projection, while the overall supply of Latino physicians will
      increase by nearly 30% by 2020, that growth will be dwarfed by the 74% growth in
      the Latino population over the same time. In the worst-case projection, the
      actual number of Latino physicians will decrease from the 1999 figure of 3,578 to
      3,448 by 2020, while the Latino population continues to grow. CONCLUSIONS: (1)
      The Latino USMG supply must be markedly increased in the number of first-year
      matriculants in both California and out-of-state schools. (2) The issue of Latino
      IMGs requires special attention, and may provide a temporary solution to the
      Latino physician shortfall. (3) Non-Latino physicians need to be prepared to be
      culturally effective with a large and growing Latino patient population.

PMID- 10926026
TI  - The influence of task formats on the accuracy of medical students' self
      assessments.
AB  - PURPOSE: Accurate self-assessment is an essential skill for the self-directed
      learning activities and appropriate patient referral decisions of practicing
      physicians. However, many questions about the characteristics of self-assessment
      remain unanswered. One is whether self-assessment is a generalizable skill or
      dependent on the characteristics of the task. This study examines the self
      assessment skills of medical students across two task formats: performance-based
      and cognitive-based. METHOD: In 1997 and 1998, fourth-year medical students at
      the University of Michigan assessed their own performances on ten stations of a
      clinical examination. The examination used two formats: performance tasks (the
      examination or history taking of standardized patients) and cognitive tasks
      (interpreting vignettes or test results and then answering paper-and-pencil
      questions). Three measures of self-assessment accuracy were used: a bias index
      (average difference between the students' estimates of their performances and
      their actual scores), a deviation index (average absolute difference between
      estimate and actual score), and an actual score-estimate-of-performance
      correlation (the correlation between the estimate and actual scores). RESULTS:
      The student bias and deviation indices were similar on the cognitive and the
      performance tasks. The correlations also indicated similarity between the two
      types of tasks. CONCLUSION: The results indicate that the format of the task does
      not influence students' abilities to self-assess their performances, and that
      students' self-assessment abilities are consistent over a range of skills and
      tasks. The authors also emphasize the importance of sampling tasks while
      conducting self-assessment research.

PMID- 10926027
TI  - Interns' self-evaluations compared with their faculty's evaluations.
AB  - The accuracy with which individuals evaluate and judge their knowledge and skills
      is an important component of adult and life-long learning. This study compared
      the evaluations that interns made of themselves with those made by their faculty.

PMID- 10926028
TI  - The ability of a medical school admission process to predict clinical performance
      and patients' satisfaction.
AB  - PURPOSE: The authors evaluated the ability of a two-step admission process to
      predict clinical performance and patients' satisfaction on a third-year objective
      structured clinical examination (OSCE). METHOD: Subjects were three matriculating
      classes (1993, 1994, 1995) at one medical school. Data for the classes were
      analyzed separately. Independent variables were the Academic Profile (AP), an
      initial ranking of applicants based on grade-point ratio and MCAT scores, and the
      Selection Profile (SeP), an average of three interview scores. Interviews were
      offered based on AP rank, and admission was offered based on SeP rank. Dependent
      variables were total score on the faculty-graded portion of the OSCE and
      patients' satisfaction scores completed by the OSCE standardized patients. The
      authors evaluated the correlations between AP and OSCE performance and between
      SeP and OSCE performance. The authors also compared the OSCE performances of
      students whose ranks changed after interviews (SeP rank < AP rank or SeP rank >
      AP rank). The level of significance was adjusted for the number of comparisons
      (Bonferroni method). RESULTS: Complete data were available for 91% of eligible
      students (n = 222). No class showed a significant correlation between either AP
      or SeP rankings and OSCE performance (p > .01). Likewise, there was no difference
      in OSCE performance for students whose ranks changed after the interview.
      CONCLUSIONS: The admission ranking and interview process at this medical school
      did not predict clinical performance or patients' satisfaction on this OSCE.

PMID- 10926029
TI  - Stress management in medical education: a review of the literature.
AB  - PURPOSE: To review systematically clinical studies providing empirical data on
      stress-management programs in medical training. METHOD: The authors searched
      Medline and PSYCHINFO from 1966 to 1999. Studies were included if they evaluated
      stress-management programs for medical trainees (medical students, interns, or
      residents); reported empirical data; and had been conducted at allopathic medical
      schools. RESULTS: Although the search yielded over 600 articles discussing the
      importance of addressing the stress of medical education, only 24 studies
      reported intervention programs, and only six of those used rigorous scientific
      method. Results revealed that medical trainees participating in stress-management
      programs demonstrated (1) improved immunologic functioning, (2) decreases in
      depression and anxiety, (3) increased spirituality and empathy, (4) enhanced
      knowledge of alternative therapies for future referrals, (5) improved knowledge
      of the effects of stress, (6) greater use of positive coping skills, and (7) the
      ability to resolve role conflicts. Despite these promising results, the studies
      had many limitations. CONCLUSION: The following considerations should be
      incorporated into future research: (1) rigorous study design, including
      randomization and control (comparison) groups, (2) measurement of moderator
      variables to determine which intervention works best for whom, (3) specificity of
      outcome measures, and (4) follow-up assessment, including effectiveness of future
      patient care.

PMID- 10926030
TI  - Scientific publications at a Turkish medical school.
AB  - The authors studied the scientific publishing trend for 1991 to 1998 at Turkey's
      Marmara University School of Medicine. Although publications increased both in
      real numbers and in ratios per faculty member, most were not original, peer
      reviewed articles. Mere quantity of publications cannot accurately reflect a
      school's research reputation.

PMID- 10926031
TI  - Introducing residents to a career in management: the Physician Management
      Pathway.
AB  - To prepare their students and residents for the practice of medicine in a rapidly
      changing environment, medical educators must teach the business of medicine as
      well as the science and art of medicine. Recognizing the value of and demand for
      physician leaders, the authors sought to introduce residents to diverse aspects
      of medical administration within the context of an academically rigorous internal
      medicine residency program. The Physician Management Pathway (PMP) was developed
      in 1997 to expose interested residents to the management concepts employed by
      physician managers; to help physician trainees begin to develop the leadership
      and technical skills they will use as physician managers; to provide career
      mentoring; to provide experiences that enrich the resident's training in clinical
      medicine; to enhance resident-directed educational activities; and to produce
      physicians who can successfully work in any health care environment. The PMP
      curriculum consists of a monthly seminar series, a preceptorship experience in
      the second year of residency, and a supervised project in the third year. The
      program was not designed to provide competency in management, but rather is
      intended to provide an opportunity for new physicians to explore options in this
      exciting and changing profession.

PMID- 10926032
TI  - Using literature to help physician-learners understand and manage "difficult"
      patients.
AB  - Despite significant clinical and research efforts aimed at recognizing and
      managing "difficult" patients, such patients remain a frustrating experience for
      many clinicians. This is especially true for primary care residents, who are
      required to see a significant volume of patients with diverse and complex
      problems, but who may not have adequate training and life experience to enable
      them to deal with problematic doctor-patient situations. Literature--short
      stories, poems, and patient narratives--is a little-explored educational tool to
      help residents in understanding and working with difficult patients. In this
      report, the authors examine the mechanics of using literature to teach about
      difficult patients, including structuring the learning environment, establishing
      learning objectives, identifying teaching resources and appropriate pedagogic
      methods, and incorporating creative writing assignments. They also present an
      illustrative progression of a typical literature-based teaching session about a
      difficult patient.

PMID- 10926033
TI  - Group process: the black box of studies on problem-based learning.
AB  - A considerable number of medical schools worldwide have implemented, at least in
      part, a problem-based learning (PBL) approach in their curricula. Research to
      date has largely neglected the issue of the actual activities and learning
      processes that mediate and moderate the relationship between these programs and
      their cognitive outcomes. In this essay the authors discuss the few studies that
      have empirically investigated what students actually do in PBL tutorials, which
      arguably is the pivotal mediating process. These studies demonstrate that it is
      possible to observe, identify, and describe group activities (such as
      brainstorming and the joint identification of learning issues) that promote
      interactionally shared and achieved cognition. However, such studies have been
      confined to case studies in which isolated fragments of tutorials have been
      analyzed and described. Future studies need to provide a broader description and
      analysis of actually performed cognitive activities in all relevant phases of the
      entire PBL process.

PMID- 10926034
TI  - Screening applicants for a rural medical education program.
AB  - The goal of the Rural Medical Education (RMED) Program of the University of
      Illinois College of Medicine at Rockford is to train rural family physicians.
      This article describes the screening instrument developed by RMED to identify
      appropriate candidates.

PMID- 10926035
TI  - Prevention for the 21st century: setting the context through undergraduate
      medical education.
AB  - The generation of medical students now being taught will be practicing into the
      middle of the next century. They will be expected to provide an expanding array
      of clinical preventive services and be responsible for the health and well-being
      of entire populations and communities. Although prevention principles are being
      taught in many contexts, most medical schools do not have adequate curriculum
      tracking systems that allow them to track the delivery of education and training
      in disease prevention and health promotion. The Bureau of Health Professions of
      the Health Resources and Services Administration (HRSA) and the Association of
      Teachers of Preventive Medicine have worked on several projects that have
      culminated in the development of a set of core competencies in preventive
      medicine for undergraduate medical education. In 1997 they convened a task force
      of medical educators from a broad array of basic science and clinical disciplines
      representing major U.S. medical teaching societies. The task force reviewed and
      updated the 1984 Inventory of Knowledge and Skills Relating to Disease Prevention
      and Health Promotion so that it would be relevant to faculty in diverse specialty
      areas and could be integrated throughout the medical curriculum. They then
      created a list of competencies that are essential from the perspective of each
      discipline and all disciplines. The article gives the context for teaching
      preventive medicine, presents the core competencies, and serves as the
      introduction to a supplement to Academic Medicine on teaching preventive medicine
      throughout the undergraduate medical curriculum.

PMID- 10926036
TI  - Prevention education and evaluation in U.S. medical schools: a status report.
AB  - The Prevention Curriculum Assistance Program (PCAP) was initiated to help U.S.
      medical schools examine the extent to which they are evaluating the learning of
      medical students about disease prevention/health promotion. A survey was sent to
      all 144 allopathic and osteopathic medical schools, with an overall response rate
      of 68%. The results revealed more emphasis on teaching and evaluating the
      learning of medical students in the areas of clinical preventive services and
      quantitative methods, and less emphasis on the community dimensions of medical
      practice and health services organization and delivery. Written tests and
      unstructured observation are the most common methods of evaluation. Fewer than
      half of all respondents were satisfied with the quality of their assessment of
      student achievement in any of the four domains of prevention education. More than
      30% expressed a desire to receive assistance with designing curricula and/ or
      evaluation methods in each of the four content areas examined. Several indicated
      their willingness to assist colleagues who want to improve their prevention
      curricula and/or measurement strategies. This study identified a need for more
      attention and support for prevention education and evaluation programs.
      Curriculum leaders can help by designating prevention a priority area and
      appointing faculty to be responsible for monitoring the content and quality of
      prevention teaching throughout the curriculum. Resources such as the Internet can
      be utilized to establish a network whereby medical schools can collaborate to
      improve their educational programs and evaluation methods in prevention.

PMID- 10926037
TI  - Preventive medicine 2000: changing contexts and opportunities.
AB  - The teaching of preventive medicine in the medical school curriculum occurs both
      in independent and in interdisciplinary courses and units. A survey was conducted
      to examine the changes in preventive medicine context, content, and allotted
      hours that have occurred in the transition from the traditional Flexnerian
      curriculum to the more interdisciplinary, centrally controlled curriculum. Data
      on medical school curricula for 1990-91, 1993-94, 1995-96, and 1998-99 were
      examined for the 126 U.S. and 16 Canadian medical schools. By 1998-99, 35 schools
      moving to the new interdisciplinary format had retained preventive medicine
      teaching as a separate course, although the courses usually had incorporated
      topics that went beyond the traditional ones. In another 35 schools, preventive
      medicine hours had been lost in the transition; but in 25 of these new courses it
      was clear that preventive medicine played a very significant role. It can be
      assumed that the lost hours were more than replaced as preventive medicine
      concepts permeated these courses. Of greatest importance were the hallmark
      courses of the six nontraditional curricula that had designated preventive
      medicine a major-theme course. However, at ten schools, preventive medicine
      listings disappeared in the move to nontraditional curricula. Preventive medicine
      educators must step forward to use curricular restructuring to expand the role of
      preventive medicine in the curricula of their institutions, whether in stand
      alone or in interdisciplinary courses. The goal, as always, is to provide future
      physicians with the knowledge and skills they need to provide proper care to
      their patients.

PMID- 10926038
TI  - Evaluation methods for prevention education.
AB  - The knowledge, skills, and attitudes associated with prevention cut across
      clinical disciplines. Thus, they are often subsets of disciplines not otherwise
      present in the traditional curriculum (e.g., epidemiology or statistics) or
      considered the province of many disciplines (e.g., risk reduction or cancer
      screening). Evaluation of elements of prevention education can often become lost
      in the myriad other outcomes that are assessed in students, or they are
      intermingled with other content and skills. This article highlights the value of
      assessing students' competence in prevention knowledge, skills, and attitudes,
      provides general guidance for programs interested in evaluating their prevention
      instructional efforts, and gives specific examples of possible methods for
      evaluating prevention education. While it is important to tailor assessment
      methods to local institutional objectives, it is possible to share assessment
      methods and materials regionally and nationally. Sharing problems, as well as
      successes, encountered in developing appropriate assessment methods will advance
      the field of evaluation of prevention curricula.

PMID- 10926039
TI  - Faculty development and support needed to integrate the learning of prevention in
      the curricula of medical schools.
AB  - Comprehensive coverage of prevention-related topics in the curricula of medical
      schools is important for the training of future physicians; however, the changes
      needed in educational programs to include such topics are likely to challenge
      many institutions. Faculty members are central to the successful adoption of any
      new curricular paradigm, yet many of the impediments to change are also likely to
      be found within the faculty ranks. Achieving major curricular change requires
      institution leaders to define a new vision and allocate sufficient resources to
      support faculty efforts. Appropriate steps should be taken to actively involve
      the faculty early in the process of change and to recruit stakeholders from
      within the faculty ranks to play prominent roles. The educational models should
      be based on educationally and scientifically sound underpinnings that will
      facilitate acceptance of the models by the faculty, and faculty members must be
      offered appropriate opportunities to develop the skills to successfully implement
      the models. A school-wide faculty development program should address
      organizational development, instructional development, and personal development.
      The expertise needed to design and implement these activities may be secured from
      within or outside the institution. Individuals who have played key roles in the
      curricular change process must be rewarded and given appropriate recognition for
      their contributions. These steps will help in the successful integration of
      prevention-related topics into the curriculum, which will add a much-needed
      dimension, resulting in students' being better prepared to address the needs of
      their patients and the community.

PMID- 10926040
TI  - Communication skills for preventive interventions.
AB  - Effective communication relevant to preventive services and practices has at its
      basis the physician's skills in not only basic history taking and data collection
      but also relationship building, facilitation, negotiation, and partnership. These
      skills, fundamental to doctor-patient communication, are now routinely and
      systematically taught in many U.S. medical schools. This article defines and
      examines a communication model for enhancing the provision and adoption of
      preventive practices in the primary care setting and discusses teaching that
      model in the medical school context. Within the office visit, broad areas for
      communication tasks important to providing preventive services are defined as:
      (1) the medical interview and preventive counseling; (2) working with patients to
      change unhealthy behaviors, promote healthy behaviors, and enhance adherence; and
      (3) communication related to office procedures for screening and prevention.
      Within each of these areas, communication and counseling skills and approaches
      are defined, and examples of associated prevention activities are provided.
      Methods for integrating communication skills for prevention into the medical
      school curriculum are discussed, and examples at Dartmouth, Brown, and MCP
      Hahnemann medical schools are presented.

PMID- 10926041
TI  - Integrating prevention education into the medical school curriculum: the role of
      departments of family medicine.
AB  - Departments of family medicine--including departments of family and community
      medicine, departments of family and preventive medicine, and departments of
      family practice-at U.S. medical schools regularly participate in teaching
      prevention principles to students, using a variety of formats and methods.
      Required clinical experiences (i.e., clerkships and preceptorships), required
      nonclinical courses, and electives frequently include prevention content.
      Collaborative interdisciplinary clerkships, interdisciplinary nonclinical
      courses, and courses directed by other departments also enable family medicine
      faculty to teach prevention principles. This article describes examples of
      innovative educational programs in which family medicine faculty teach prevention
      content to medical students. Directions for future educational efforts by family
      medicine faculty in the prevention area are proposed.

PMID- 10926042
TI  - Teaching prevention in internal medicine clerkships.
AB  - The teaching of prevention to students in internal medicine has come into much
      sharper focus in the past decade or so, and the ongoing development of a strong
      scientific base for clinical preventive services has led to broad acceptance of
      the principles and practice of prevention in internal medicine. This article
      reviews the rationale for including prevention in the clinical medicine
      clerkship, summarizes current guidelines, presents examples of curricula in
      several medical schools, and proposes a future direction for more fully
      integrating prevention teaching in the internal medicine clerkship into the rest
      of the medical school curriculum. Internal medicine clerkships present many
      opportunities for teaching and learning about the broad scope of prevention, from
      individual preventive services to improving the health of groups of patients. But
      individual clinical clerkships cannot do the job in isolation from each other.
      More attention should be directed to coordinating the teaching of prevention
      among the clinical disciplines and across the entire four-year medical school
      curriculum, so that students graduating from medical school will leave with the
      thorough understanding they need to contribute to the health of the public in the
      health care system of the future.

PMID- 10926043
TI  - Teaching prevention in pediatrics.
AB  - Pediatrics has attempted to inculcate the "culture of prevention" into practice,
      both through anticipatory guidance in well-child care and through behavioral
      interventions in sick care. The effectivenesses of many components of well-child
      care have not been conclusively demonstrated, particularly in health education,
      counseling, and anticipatory guidance, nor has teaching prevention in pediatrics
      been thoroughly evaluated. This article reviews methods of teaching prevention in
      pediatrics and highlights innovative programs. Teaching programs use the wide
      range of approaches now common in medical education, in a variety of inpatient
      and outpatient sites. Programs across the country are trying new approaches to
      teaching traditional topics or are introducing new topics into their curricula.
      Examples of specific programs are given, organized by the themes of the programs.
      The field needs to develop in three major directions. First, there is a need to
      develop competencies and curricula in prevention issues of contemporary
      importance, including the new morbidities, cross-cultural issues, cost
      effectiveness, quality of care, and practice in managed care and other community
      settings. Second, further work is needed to evaluate programs and measure
      educational outcomes. This feedback must in turn be used to redefine
      competencies, curricula, and programs, Third, there needs to be an accessible
      clearinghouse, and educational tools need to be disseminated. To be effective, a
      curriculum for prevention in pediatrics cannot stand alone, but must be part of a
      vertically and horizontally integrated curriculum. Further, creating horizontally
      and vertically integrated curricula in prevention teaching across disciplines
      should be the standard.

PMID- 10926044
TI  - Integrating prevention into obstetrics/gynecology.
AB  - Obstetricians and gynecologists play an important role in preventive medicine. A
      great deal of obstetrics and gynecology is dependent on the principles of
      preventive medicine, such as understanding populations, risk profiling,
      epidemiology, and statistics as they pertain to screening programs and
      prevention. Thus, it is reasonable that an ob-gyn clerkship be an integral part
      of a program to teach preventive medicine in a medical school. This article
      presents information about formats used to teach preventive medicine in ob-gyn,
      illustrated by specific programs at medical schools across the country. It also
      provides information about publications that are useful for designing and
      creating programs in introduce and/or integrate preventive medicine into ob-gyn
      clerkships and other parts of the undergraduate medicine curriculum.
      Obstetricians and gynecologists spend the majority of their time in the office,
      and most of their patient visits can be classified as preventive medicine visits.
      Medical students' education needs to reflect that focus. Among other things, ob
      gyn must develop training directed toward students who do not intend to become
      obstetricians. A rotation in ob-gyn may be the only exposure a student has to
      health care that is specifically for women. Therefore, that clerkship must focus
      on preventive medicine for women as well as on treatment.

PMID- 10926045
TI  - Teaching prevention in surgery--is it an oxymoron?
AB  - Although surgery is not often thought of as the optimal pathway to health, it
      nonetheless can play a key role in many facets of medical student education
      involving disease prevention. This article defines the scope of the surgeon's
      involvement in teaching disease prevention and health promotion to medical
      students, enumerates possible learning objectives that may be (and often already
      are) incorporated into their surgical education, and describes seven examples of
      programs that have used innovative methods to include prevention teaching in
      their surgery curricula. There should be specific educational standards regarding
      prevention within the curriculum of each clinical specialty, and educational
      programs should be evaluated with outcome measures. Prevention teaching should
      not be performed differently and apart from current interventional teaching, but
      needs to be incorporated within it. Medical education occurs increasingly in
      outpatient settings. Even in the surgical disciplines, outpatient surgery and
      office hours are being incorporated increasingly into the clerkship experience.
      The resulting exposures to large numbers of patients with mostly early stages of
      surgical disorders afford excellent opportunities for surgeons to emphasize to
      both patients and students many of the important aspects of prevention.

PMID- 10926046
TI  - Teaching prevention through electives.
AB  - The Liaison Committee on Medical Education (LCME) accreditation standards affirm
      that the medical school curriculum should include elective courses to supplement
      the required courses and provide opportunities for students to pursue individual
      academic interests. The breadth of opportunities in preventive medicine and
      population health is extensive as students seek rotations at health departments,
      rural and urban community health centers, community agencies, occupational health
      sites, schools, and abroad. A growing number of students choose to participate in
      MD/MPH dual-degree programs. This article describes four prototypes that foster
      student learning in preventive medicine: population health, international health,
      American Medical Student Association opportunities, and public health degree
      programs. These four types of electives enable students to participate in the
      front lines of preventive services through experiential learning in: community
      and population health both at home and abroad, continuous quality improvement,
      organization and behavioral change, interprofessional teamwork, and health care
      policy. For those with particular interests in population health and preventive
      medicine, an increasing number of medical schools offer dual MD/MPH programs,
      either in conjunction with schools of public health or in graduate programs in
      public health.

PMID- 10926048
TI  - Resources for teaching and learning prevention.

PMID- 10926047
TI  - Putting it all together: building a four-year curriculum.
AB  - A four-year curriculum in preventive medicine would require planning, but all the
      components are already available. This article outlines a four-part plan: develop
      the desired objectives or competencies; present the basics in years one and two
      of the curriculum; in years three and four make health promotion/disease
      prevention (HPDP) and the population perspective relevant to the practice of
      medicine; and, finally, develop a mechanism to track the curriculum and then
      improve it. Core competencies have already been developed, through joint
      activities of the Association of Teachers of Preventive Medicine (ATPM) and the
      Bureau of the Health Professions of the Health Resources and Services
      Administration (HRSA), and articles about teaching preventive medicine in
      multiple disciplines throughout the curriculum are published elsewhere in this
      supplement. Schools across the United States and Canada have innovative programs
      in place that can serve as models, and there are feasible approaches to
      monitoring the programs.

PMID- 10926049
TI  - Pharmacologic characteristics of ideal antidepressants in the 21st century.
AB  - The availability of drugs for use as antidepressants has expanded greatly in the
      past 2 decades. Not only has the number of drugs increased but so has the
      diversity in associated pharmacologic effects. Drug development for central
      nervous system agents is proceeding at an accelerated pace. The coming decades
      hold the promise for the introduction of newer antidepressants that have novel
      mechanisms of action, improved adverse event profiles, and expanded indications.
      Unfortunately, the ideal antidepressant is yet to be formulated. Pharmacologic
      characteristics for desirable improvements are discussed relative to the
      currently available drugs.

PMID- 10926051
TI  - Enhancing pharmacologic effects in the treatment of depression in women.
AB  - The prevalence of depressive disorders in women is twice that in men. This gender
      difference emerges around the time of puberty and persists through the
      childbearing years. Reproductive events and psychosocial factors are important
      influences on depression in women. Women often present with atypical depressive
      symptoms and comorbid disorders that can complicate both diagnosis and treatment.
      Sex differences in pharmacokinetics have been noted, as well as differences in
      antidepressant treatment response. While sleep disturbances, sexual dysfunction,
      and weight gain may be part of the constellation of depressive symptoms, they are
      also important considerations in selecting a treatment option for depressed
      women.

PMID- 10926050
TI  - New indications for antidepressants.
AB  - The second and third generation of antidepressants, i.e., the selective serotonin
      reuptake inhibitors, nefazodone, venlafaxine, and mirtazapine, are proving to be
      useful in a variety of seemingly diverse disorders, including most anxiety
      disorders. In addition to receiving approval from the U.S. Food and Drug
      Administration (FDA) for major depressive disorder, some of the newer
      antidepressants have received FDA approval for other disorders, e.g., generalized
      anxiety disorder (venlafaxine), bulimia nervosa (fluoxetine), obsessive
      compulsive disorder (fluvoxamine, paroxetine, sertraline, and fluoxetine), social
      phobia (paroxetine), panic disorder (sertraline, paroxetine), and posttraumatic
      stress disorder (sertraline). In controlled studies, these agents have also shown
      usefulness in premenstrual dysphoric disorder, borderline personality disorder,
      obesity, smoking cessation, and alcoholism. This article describes the new and
      potential indications for recently developed antidepressants and the studies that
      suggested these indications.

PMID- 10926052
TI  - Sexual side effects of antidepressants.
AB  - Patients with depressive disorders frequently have concurrent sexual problems.
      The sexual dysfunction is often masked by the mood disorder, and many patients
      have difficulty discussing these problems openly. Thus, sexual dysfunction often
      is detectable only by careful inquiry. The relationship between sexual
      dysfunction and depressive disorders is further complicated by antidepressant
      therapy, which itself may cause sexual dysfunction, increasing the risk of
      noncompliance and relapse. This article reviews studies indicating that
      antidepressants may cause 30% to 40% of patients who take them to develop some
      degree of sexual dysfunction. Management strategies for alleviating sexual
      dysfunction as a complication of antidepressant treatment are discussed in terms
      of supporting research studies as well as practicality. Spontaneous resolution of
      antidepressant-induced sexual dysfunctions rarely occurs, and dose reductions may
      jeopardize the antidepressant effect. Antidotes, drug holidays, and timing sexual
      relations with respect to antidepressant dose are effective for some patients,
      but only a few of these strategies have been studied with double-blind paradigms.
      Switching to antidepressants that cause sexual dysfunction at lower rates and
      data comparing rates of sexual dysfunction among antidepressants are discussed.

PMID- 10926053
TI  - Weight gain and antidepressants.
AB  - Weight gain during antidepressant treatment can be either a sign of improvement
      in patients who have weight loss as a symptom of depression or a residual symptom
      in patients who overeat when depressed. However, significant weight gain during
      the acute phase of treatment or weight gain that continues despite achieving full
      remission of depressive symptoms is likely to be a side effect of antidepressant
      treatment. Weight gain is a relatively common problem during both acute and long
      term treatment with antidepressants, and it is an important contributing factor
      to noncompliance. This article will review the literature with regard to the
      relative risk for weight gain of antidepressants. It appears that tricyclic
      antidepressants (TCAs) and perhaps monoamine oxidase inhibitors (MAOIs) may be
      more likely to cause weight gain than the selective serotonin reuptake inhibitors
      (SSRIs) or the newer antidepressants, with the exception of mirtazapine, which
      may be placed between the SSRIs and the TCAs in terms of relative risk for weight
      gain. Paroxetine may be more likely to cause weight gain than the other SSRIs
      during long-term treatment, and bupropion and nefazodone may be less likely to
      cause weight gain than the SSRIs in the long term, although more studies are
      necessary to confirm these impressions.

PMID- 10926054
TI  - New strategies for treating chronic depression.
AB  - This article provides an update on the diagnosis of chronic depression subtypes,
      the clinical and public health significance of chronic depression, and a review
      of what is known about its treatment. The efficacy of antidepressant medications
      for pure dysthymia and double depression has been established, yet fewer than 50%
      of patients have achieved full remission with a single agent. Traditional
      antidepressant psychotherapies appear to have limited effectiveness for chronic
      depression. In one recent study, a combination of cognitive behavioral analysis
      system of psychotherapy and a newer antidepressant, nefazodone, yielded the
      highest response and remission rates ever reported in this population (73%
      response rate, 48% remission rate in an intent-to-treat sample). This combination
      merits further study for treatment of chronic depression.

PMID- 10926055
TI  - Treatment issues related to sleep and depression.
AB  - In the management of depression, the role of sleep and sleep disturbances is
      important for several reasons. The same neurotransmitter systems that regulate
      mood, interest, energy, and other functions that may be disturbed in depression
      also regulate sleep. Sleep disturbances may be responsive to treatment with some
      antidepressants and may be worsened during treatment with other antidepressants.
      Serotonergic neurons play a critical role in modulating the onset and maintenance
      of sleep, and it is thought that insomnia in depression is caused by dysfunction
      of serotonergic systems. For a significant minority, SSRIs can have negative
      effects on sleep patterns resulting in insomnia that requires concomitant
      sedatives or anxiolytics. By contrast, agents that block the serotonin type 2 (5
      HT2) receptor have beneficial effects on depressive insomnia. For example, a
      recent 8-week study comparing the effects of nefazodone and fluoxetine on sleep
      disturbances in outpatients with nonpsychotic depression and insomnia found that
      fluoxetine was associated with approximately a 30% increase in the number of
      nocturnal awakenings whereas nefazodone was associated with about a 15% decrease,
      a net difference of 45%. Long-term studies must be conducted to determine whether
      sleep benefits provided by the newer antidepressants will continue past the acute
      treatment phase.

PMID- 10926056
TI  - Inner city disadvantage and family functioning.
AB  - The co-existence of types of social, environmental and family disadvantage and
      domains of family dysfunction is explored through individual interviews and use
      of the Family Assessment Device in a cross-sectional study of 143 inner city
      families. The dependence upon social welfare by the family and the overall degree
      of disadvantage experienced both correlate significantly with all forms of family
      dysfunction. Marital disruption, poor physical care of the home or of the
      child(ren) and poor quality of mothering correlate significantly with
      difficulties both in role allocation and in affective involvement. Those families
      suffering more types of environmental disadvantage are more likely also to be
      dysfunctional in each domain of family life. Some possible mechanisms for these
      associations are highlighted and their implications for planning of effective
      interventions discussed.

PMID- 10926057
TI  - War trauma and psychopathology in Bosnian refugee children.
AB  - This paper describes the pattern of psychopathology in a sample of 95 children of
      8-13 years, who had experienced war in Bosnia. The children were assessed with a
      battery of standardised measures during a psychosocial support programme in
      Northern Greece. They either came from refugee families (44%) or had suffered
      significant family loss (a parent had been killed in 28% and the father was
      injured or absent in 27% of cases). Children recalled a substantial number of war
      traumatic experiences. According to previously established cut-off scores on self
      report measures, 45 children (47%) scored within the clinical range on the
      Depression Self-Rating Scale for Children, 28 (23%) on the Revised Children's
      Manifest Anxiety Scale, and 65 (28%) on the Impact of Event Scale (IES) measuring
      PTSD reactions. There was a significant association between the number of war
      traumatic experiences and the intrusion and avoidance scores on the IES. The
      findings are discussed in relation to setting up intervention programmes for
      children victims of war and their families.

PMID- 10926058
TI  - The peer relations of disruptive children with reference to hyperactivity and
      conduct disorder.
AB  - Literature reviews indicate that children with disruptive behaviour disorders
      have peer relationship problems, but little information is available concerning
      the differential effects of hyperactivity and conduct disorder on peer
      relationships. Using a database from North of England research, this paper uses
      standard frequency analysis complemented by multivariate analyses to explore the
      independent effects of pervasive hyperactivity and conduct disorder on the
      sociometry of peer relations among 7- to 8- and 11- to 12-year-olds. The findings
      suggest that (a) social isolation in 7-8-year-olds shows no significant
      association with hyperactivity. However there is a significant association with
      conduct disorder in 11-12-year-olds. (b) Rejection is not significantly
      associated with hyperactivity alone nor with conduct disorder alone in 7-8-year
      olds. However, it is associated with a combination of hyperactivity and conduct
      disorder. In 11-12-year-olds rejection is associated with conduct disorder alone
      and with conduct disorder and hyperactivity in combination. It is also associated
      with low cognitive ability alone and in combination with conduct disorder.
      Overall, these findings provide some limited evidence of adverse sociometric
      responses to both hyperactivity and below average cognitive ability. However, in
      the at-risk samples analysed here, conduct disorder emerges as the most powerful
      independent predictor of isolation and rejection, and this is especially so among
      older children.

PMID- 10926059
TI  - Recommended care for young people (15-19 years) after suicide attempts in certain
      European countries.
AB  - Data on recommended care for young people aged 15-19 years after attempted
      suicide from nine European research centres during the period 1989-1992 were
      analysed in terms of gender, history of previous suicide attempt and methods
      used. Altogether 438 suicide attempts made by 353 boys and 1,102 suicide attempts
      made by 941 girls were included. Analyses of the total data from all centres
      showed that young people with a history of previous suicide attempt and those
      using violent methods had significantly higher chance of being recommended
      aftercare than first-time attempters or those choosing self-poisoning. There were
      no significant differences of being recommended care between genders. Logistic
      regression analyses of the material were performed and the results were similar.
      Both having previous attempted suicide (odds ratio 2.0, 95% CI 1.53-2.61) and
      using "hard" methods (odds ratio 1.71, 95% CI 1.49-1.96) were significantly
      associated with increased possibility of being recommended aftercare. When
      individual centres were analysed, large disparities of recommended care after
      suicide attempts were found and there were no uniform criteria of recommending
      care for young suicide attempters in Europe.

PMID- 10926061
TI  - Early psychopathological signs in bulimia nervosa. A retrospective comparison of
      the period of puberty in bulimic and control girls.
AB  - While bulimia nervosa (BN) typically begins in girls during late adolescence,
      puberty and associated developmental changes have been linked to negative body
      image and onset of a variety of psychological problems. This study aimed to
      identify early psychopathological signs, which could have marked the period of
      puberty in subjects whom later developed BN. In a case control study, we compared
      49 girls with BN according to DSM-IV, aged between 18 and 20 years, to 49 girls
      of the same age, who were free of any past or current psychiatric diagnosis.
      Psychiatrists or clinical psychologists, using a semi-structured clinical
      interview including retrospective assessment of the emotional and behavioural
      changes that had occurred in puberty evaluated both groups. Before the onset of a
      clinical eating disorder, the subjects with BN presented significantly more often
      than controls weight related concerns, attitudes of withdrawal and social
      isolation, and negative changes in their body image and self-image, as well as in
      their relationships with siblings and peers. The results suggest that early
      psychological distress precedes the onset of an eating disorder in many cases,
      and that prevention efforts should be directed towards peripubertal
      psychopathology.

PMID- 10926060
TI  - Young children with Velo-Cardio-Facial syndrome (CATCH-22). Psychological and
      language phenotypes.
AB  - This is the first clinical description of a detailed psychological, speech, and
      language phenotype of four young children (< 5 years) with Velo-Cardio-Facial
      syndrome (VCFS) due to a deletion on chromosome 22 (22q11.2). The reported
      elevated risk of developing schizophrenia or bipolar disorder in adolescence for
      individuals with this chromosomal deletion led us to examine the psychiatric and
      cognitive status of young children with VCFS. Our observations suggest a
      phenotype comprised of a borderline to mildly retarded level of intellectual
      functioning, a language delay, a general deficit in social initiation,
      difficulties with attention/concentration, and a perturbed train of thought.

PMID- 10926062
TI  - Social competence and emotional/behavioural problems in children of psychiatric
      inpatients.
AB  - The social competence and emotional/behavioural problems among 80 5-16-year-old
      children of 46 inpatients with various psychiatric disorders were assessed by the
      parents using a Swedish version of the Child Behavior Checklist (CBCL). The
      ratings of these children were compared to a normative sample of school children,
      but also whether type of psychiatric disorder among the parents was related to
      psychosocial functioning in their children. Fifty percent of the parents had a
      psychotic disorder; other common diagnoses were depressive, neurosis or
      personality disorders. Overall, children of psychiatric inpatients were perceived
      by the parents to be less socially competent and to have more emotional/
      behavioural problems than school children in the same age groups. However, 25% of
      the children of psychiatric parents were rated as having more severe problems
      (corresponding to the 90th percentile of the normative sample). About 15% of the
      children had total problem levels comparable to child psychiatric samples, but
      only 5% did actually receive ongoing help from the child psychiatric service.
      Parents with a depressive disorder or a crisis reaction also regarded their
      children to be more anxious/depressed, and to have more social problems than
      those of parents with other psychiatric disorders. Four CBCL items were found to
      be strong predictors of being a child of a psychiatric parent or parent in the
      normative sample. We suggest that the CBCL might be a valuable clinical tool in
      the screening and identification of those children of psychiatrically ill
      parents, who show more extreme problem scores and therefore might need help
      because of psychological problems.

PMID- 10926063
TI  - Predicting type of psychiatric disorder from Strengths and Difficulties
      Questionnaire (SDQ) scores in child mental health clinics in London and Dhaka.
AB  - A computerised algorithm was developed to predict child psychiatric diagnoses on
      the basis of the symptom and impact scores derived from Strengths and
      Difficulties Questionnaires (SDQs) completed by parents, teachers and young
      people. The predictive algorithm generates "unlikely", "possible" or "probable"
      ratings for four broad categories of disorder, namely conduct disorders,
      emotional disorders, hyperactivity disorders, and any psychiatric disorder. The
      algorithm was applied to patients attending child mental health clinics in
      Britain (N = 101) and Bangladesh (N = 89). The level of chance-corrected
      agreement between SDQ prediction and an independent clinical diagnosis was
      substantial and highly significant (Kendall's tau b between 0.49 and 0.73; p <
      0.001). A "probable" SDQ prediction for any given disorder correctly identified
      81-91% of the children who definitely had that clinical diagnosis. There were
      more false positives than false negatives, i.e. the SDQ categories were over
      inclusive. The algorithm appears to be sufficiently accurate and robust to be of
      practical value in planning the assessment of new referrals to a child mental
      health service.

PMID- 10926064
TI  - Very early onset seasonal affective disorder: a case study.
AB  - A four year old boy was referred from Scotland, with a seasonal pattern of
      depressive symptoms dating back to infancy and meeting criteria for Major
      Depressive Disorder with Seasonal Pattern by the age of three years. There was
      consistency in reports between informants and across contexts and significant
      improvement with light therapy.

PMID- 10926065
TI  - Survey on undergraduate teaching of child and adolescent psychiatry in European
      medical schools.

PMID- 10926066
TI  - The Cochrane Anaesthesia Review Group.

PMID- 10926067
TI  - Can computer-based assessment help us understand children's pain?
AB  - Good measures for self-report of pain in children are important, particularly as
      other informants tend to underestimate children's pain. This paper describes the
      development of a new computer-assisted approach to assessment of pain in
      children. The child can represent a range of different types of pains on body
      maps, and use two scales to indicate the size of the pain and the 'throb' or
      intensity. Facial expressions of associated emotions can also be incorporated
      into the figure. A series of 'pain pages' is included in the program. The pages
      allow changes in pain to be tracked over time, building up a cumulative record.
      The child can also report on different experiences and give retrospective
      accounts. Potential applications are suggested, for example in facilitating
      communication with children who find it difficult to give a clear verbal account
      of their pain, due to emotional difficulties, language or disability. Research
      directions are outlined.

PMID- 10926068
TI  - Effects of isoflurane on bacterial growth.
AB  - Anaesthetic agents have been implicated in the development of postoperative
      pneumonia, but the direct effect of volatile anaesthetics on bacterial growth has
      given contradictory results. The effects of isoflurane on the growth of
      Staphylococcus aureus and Escherichia coli were investigated under conditions
      similar to those of clinical practice, using standardized microbiological
      methods. An open anaesthetic circuit was adjusted to the normal ventilatory
      settings of an adult patient. A spray, installed on the inspiratory side of the
      circuit, ensured the delivery of isoflurane at 1.5 minimal alveolar
      concentration. The bacterial strains studied were both wild-type and reference
      strains. Bacterial inoculums were prepared to obtain a bacterial exponential
      growth of 10(3) colony-forming units per mL in 10 mL of nutritive broth. Each
      strain was studied with and without exposure to isoflurane and measured by the
      usual criteria of bacterial growth, and by bacterial regrowth after exposure to
      isoflurane. Under experimental conditions close to clinical practice, exposure to
      isoflurane did not alter bacterial growth of S. aureus and E. coli, or their
      bacterial regrowth when isoflurane exposure is over.

PMID- 10926069
TI  - Intra-articular clonidine analgesia after knee arthroscopy.
AB  - Recently, it was suggested that peripherally-mediated analgesia can be
      accomplished by the intra-articular delivery of the mu-opioid morphine or of the
      a2-agonist clonidine. This clinical study assesses the potential peripheral
      analgesic effect of the combination of morphine and clonidine after intra
      articular administration. Sixty patients (American Society of Anesthesiologists
      status I or II) undergoing arthroscopic repair of the knee during general
      anaesthesia were randomized to receive after operation, in a double-blind manner,
      either 1 mg morphine intra-articularly (group 1); 150 microg clonidine intra
      articularly (group 2); or 1 mg morphine + 150 microg clonidine intra-articularly
      (group 3); or normal saline intra-articularly (group 4) in a volume of 30 mL,
      respectively. Visual analogue pain scores (VAS), duration of analgesia as defined
      by first demand for supplemental analgesics, subsequent 24 h consumption of
      postoperative supplementary analgesics, and patient satisfaction were evaluated.
      Co-administration of morphine + clonidine (group 3) resulted in a significant VAS
      reduction at 2 h after injection compared with the other groups. There was a
      tendency towards a lower need for supplementary rescue analgesia and towards a
      more prolonged analgesia in group 3 (211 min +/- 224 min SD) compared with group
      1 (173 min +/- 197 min SD) and group 4 (91 min +/- 21 min SD). More patients were
      very satisfied with the postoperative analgesic regimen receiving the combination
      of morphine and clonidine (group 3) at 24 h postoperatively. Thus we conclude,
      that the peripheral co-delivery of an opioid and an a2-agonist will result in
      improved postoperative pain relief, when compared with each single agent given
      alone.

PMID- 10926070
TI  - Effects of pneumoperitoneum and reverse Trendelenburg position on cardiopulmonary
      function in morbidly obese patients receiving laparoscopic gastric banding.
AB  - We prospectively evaluated the effects of pneumoperitoneum and reverse
      Trendelenburg position on cardiopulmonary function in 20 ASA physical status II
      III morbidly obese patients (body mass index > 35 kg m(-2)) undergoing
      laparoscopic gastric banding. After general anaesthesia was induced, patients'
      lungs were ventilated using intermittent positive pressure ventilation (at
      measurement times, the following parameters were used: tidal volume 12 mL kg(-1)
      ideal body weight, respiratory rate of 12 bpm, an inspiratory to expiratory time
      ratio of 1:2). Haemodynamic variables, blood gas parameters, and lung/chest
      compliance were recorded: in the supine position, after induction of general
      anaesthesia (T0, baseline) and induction of pneumoperitoneum (T1); after placing
      the patient in a 25 degree reverse Trendelenburg position (T2); during the
      surgical time (T3); before deflating the abdomen (T4); after pneumoperitoneum
      resolution (T5), and before the end of anaesthesia, with the patient supine (T6).
      The PaO2, PaO2/FiO2 ratio, and lung/chest compliance decreased during the study.
      After the pneumoperitoneum had been resolved, lung/chest compliance but not
      oxygenation parameters returned to baseline values. The arterial to end-tidal CO2
      tension difference progressively increased from 0.38+/-0.3 kPa (2.85+/-2.25 mmHg)
      (T0) to 0.63+/-0.3 kPa (4.73+/-2.25 mmHg) (T6). In morbidly obese patients,
      undergoing laparoscopic gastric banding, a CO2 pneumoperitoneum markedly affected
      gas exchange and lung/chest compliance, while positioning the patient in a 25
      degree reverse Trendelenburg position had no beneficial effects.

PMID- 10926071
TI  - Can we improve the estimate of arterial PCO2 from end-tidal PCO2?
AB  - To use end-tidal PCO2 as a non-invasive estimate of arterial PCO2, one adds a
      nominal value, representing the arterial-end-tidal PCO2 difference. How much does
      one add? We hypothesized that, halving the ventilator rate and simultaneously
      doubling tidal volume, the immediate change in end-tidal PCO2 would be
      proportional to the original arterial-end-tidal PCO2 difference. We ventilated 31
      patients at 20 breaths per minute (bpm), sampled arterial blood, and changed the
      rate to 10 bpm. The change in end-tidal PCO2 was, as hypothesized, positively
      correlated to the original arterial-end-tidal difference at 20 bpm (r=0.64). End
      tidal PCO2 increased in 23 patients. Thus, in theory, this method could offer
      some improvement in the estimate of arterial PCO2 from end-tidal. However,
      because of the considerable spread of values, a separate study is needed for
      verification.

PMID- 10926072
TI  - Comparison of the effects of inhalational anaesthetic agents on sympathetic
      activity in rabbits.
AB  - The effects of inhalational anaesthetic agents on renal sympathetic nerve
      activity (RSNA) were compared in anaesthetized rabbits. Concentrations of 6%
      desflurane, 1.2% isoflurane, and 2.4% enflurane increased mean RSNA up to 32, 36
      and 44% while higher concentrations, of 12, 2.4 and 3.2% depressed it by 42, 83
      and 5%, respectively. For halothane RSNA was unchanged up to 0.8% and decreased
      by 36% at 1.6% concentration. Nitrous oxide increased RSNA up to 28% at 50%
      concentration. Maximum reductions in mean arterial pressure (MAP) were 60% for
      both 2.4% isoflurane and 3.2% enflurane, 50% for 12% desflurane and 1.6%
      halothane, while 70% nitrous oxide increased MAP by 22%. In conclusion, unlike
      the entirely depressive effects of halothane, the effects of desflurane,
      isoflurane and enflurane were biphasic involving excitation at lower
      concentrations and depression of RSNA and a reduction in MAP at higher
      concentrations. Nitrous oxide caused increases in both RSNA and MAP.

PMID- 10926073
TI  - Effect of pre-emptive analgesia on self-reported and biological measures of pain
      after tonsillectomy.
AB  - This prospective, double-blind, randomized study assessed effect of pre-emptive
      peritonsillar block in 30 ASA-I children, aged 6-12 years, of both sexes,
      scheduled for tonsillectomy. Patients were divided into three groups: those in
      group I received a sham block, whereas peritonsillar blocks with bupivacaine
      0.25% were given to the children before tonsillectomy (group II) or immediately
      after surgery had been completed (group III). Constant pain, pain on swallowing,
      blood glucose, serum epinephrine and norepinephrine concentrations were measured
      immediately after surgery and 4h after operation. Patients in group I experienced
      more pain (P< 0.05) than those in groups II and III, both in the immediate
      postoperative period and over the next 4 h. Patients in groups II and III
      experienced similar pain (P> 0.05). The pain experienced when water was swallowed
      was similar to that of the constant pain. The rise of serum norepinephrine
      concentration in group II was significantly less (P< 0.05) compared to groups I
      and III. We found both pre-emptive and postoperative block to be equally
      effective in treating postoperative pain, with pre-emptive block being more
      effective in preventing the rise in norepinephrine concentration.

PMID- 10926074
TI  - Combination of balanced and regional anaesthesia for minimally invasive surgery
      in a patient with myasthenia gravis.
AB  - A 45-year-old man with cryptorchism, who was known to suffer from generalized
      myasthenia gravis, was admitted to hospital for surgical treatment using
      laparoscopy. Such minimally invasive surgery requires good muscle relaxation.
      However, the use of neuromuscular blocking agents in patients with myasthenia
      gravis may lead to prolonged apnoea after operation, thus necessitating
      mechanical ventilation of the lungs. We used a combination of general anaesthesia
      (with desflurane), and epidural anaesthesia (with the amide local anaesthetic
      ropivacaine) to obtain excellent abdominal relaxation during surgery. Tracheal
      extubation was possible immediately after the operation and no adverse effects
      were observed. The patient was discharged from hospital on the second day after
      operation. The combination of regional and general anaesthesia for minimally
      invasive surgery in this patient permitted safe anaesthetic management.

PMID- 10926075
TI  - Combined spinal-epidural anaesthesia for Caesarean section in a paraplegic woman:
      difficulty in obtaining the expected level of block.
AB  - We describe the satisfactory use of combined spinal epidural (CSE) anaesthesia in
      the management of a 29-year-old paraplegic woman, with a spinal cord lesion at
      the T7 level, suffering from episodes of autonomic hyper-reflexia, during
      elective Caesarean section.

PMID- 10926076
TI  - Recurarization in the recovery room.

PMID- 10926077
TI  - Bradycardia, hypotension and cerebral dysfunction after spinal anaesthesia.

PMID- 10926078
TI  - Induction and maintenance of anaesthesia with sevoflurane in comparison to high
      dose opioid during coronary artery bypass surgery.

PMID- 10926079
TI  - Prediction of locoregional extension and metastatic disease in prostate cancer: a
      review.
AB  - Despite efforts to enhance the accuracy of prediction of extraprostatic disease,
      approximately 40% of the men undergoing radical prostatectomy are found at
      surgery to have non-organ-confined cancer. Predictive algorithms based on
      multivariate regression analysis and neural networks are widely available and are
      superior to our standard empirical methods of clinical staging. These algorithms
      have been validated in diverse and well-characterized patient groups. For
      enhancement of the predictive value, data input must be standardized and improved
      input variables must be incorporated. In addition to the three "classic" staging
      parameters, i.e., pretreatment prostate-specific antigen (PSA), biopsy pathology,
      and digital rectal examination, new variables now show promise in predicting
      disease extent and may be integrated in future predictive models. This review
      focuses on our present methods for prediction of locoregional spread and distant
      metastases in men with clinically localized prostate cancer.

PMID- 10926080
TI  - Outcome profiles of locoregional disease after radical prostatectomy and
      radiotherapy.
AB  - The purpose of the present study was to examine the outcome profiles of a large
      number of patients with locally advanced adenocarcinoma of the prostate following
      radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of
      1662 men who underwent RPP performed by a single surgeon between January 1972 and
      January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have
      extracapsular disease on pathological evaluation. The extent of disease was
      categorized as either specimen-confined (n = 355) or margin-positive (n = 337).
      The histological grade of the cancer was characterized using the Gleason score.
      Time to biochemical failure, defined as a prostate-specific antigen (PSA) level
      of > or = 0.5 ng/ml, and cancer-associated survival were the end points of our
      outcome analysis using the Kaplan-Meier product-limit method. The median time to
      cancer-associated death for patients with specimen-confined and margin-positive
      disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the
      patients with specimen-confined and margin-positive disease, respectively, had
      PSA failure. Prostate cancer patients with a Gleason score of 5-6, 7, and 8-10
      experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5
      years, respectively. A subset of patients undergoing adjunctive radiation therapy
      (XRT) relapsed biochemically after a median period of approximately 18 months.
      RPP provides a substantial disease-control benefit in patients with specimen
      confined cancer. The time to biochemical failure and the time to cancer
      associated death are significantly influenced by the biology of the underlying
      disease, necessitating long-term follow-up in the outcome analysis of any
      modality of treatment for prostate cancer. A benefit of early adjunctive XRT for
      local failure remains to be determined.

PMID- 10926081
TI  - Neoadjuvant and adjuvant hormone therapy for prostate cancer.

PMID- 10926082
TI  - Intermittent endocrine treatment.
AB  - Intermittent endocrine treatment or cyclic therapy of prostate cancer aims at
      prolonging survival by delaying progression to androgen independence and at
      improving quality of life by avoiding the side effects of continuous androgen
      ablation. In this paper we first review the available experimental data
      suggesting the clinical application of this therapeutic strategy and interpret
      them with caution. We then examine the published reports of phase II clinical
      studies showing the feasibility of this approach. Intermittent endocrine
      treatment is capable of inducing multiple apoptotic regressions; improvement in
      the sense of well-being and quality of life - including sexual function - is
      regularly reported. A period of 6-9 months on therapy is usually recommended; the
      mean off-therapy interval approaches 50% of the duration of the treatment cycle.
      The mean time to disease progression was 32 months. The definitive answer to the
      important question of prolonged survival awaits the completion of ongoing
      randomized studies.

PMID- 10926083
TI  - Current concepts in androgen deprivation therapy--is there a "best" endocrine
      treatment?
AB  - Androgen deprivation therapy has become the mainstay treatment for locally
      advanced and metastatic prostate cancer. Castrate testosterone levels can be
      achieved by a multitude of treatments. We performed a medline literature search
      to answer the question, is there a "best" endocrine treatment? In conclusion we
      found that the "best" endocrine therapy for advanced prostate cancer is complete
      androgen blockade (CAB) with a luteinizing hormone-releasing hormone (LHRH)
      agonist and a nonsteroidal antiandrogen.

PMID- 10926084
TI  - Management of locally advanced prostate cancer. 1. Staging, natural history, and
      results of radical surgery.
AB  - Prostate cancer presents clinically as T3 disease in about 20-25% of cases. With
      repeated screening of large parts of the male population, this proportion may
      drop in the future. Correct staging of T3 prostate cancer is difficult to
      achieve. Rectal examination and ultrasonography produce similar results.
      Overstaging in the presence of pT2 disease and understaging (pT4 or pN+ disease)
      are common and present a dilemma for proper treatment decisions. The optimal
      management of T3 prostate cancer is not known at this time. Radical prostatectomy
      for locally advanced disease can be carried out with acceptable morbidity and
      mortality and is especially beneficial in patients who have been downstaged to
      pT2 (17-30%) and in those with moderately or well-differentiated disease. In this
      group of men, historical comparison suggests that radiotherapy alone is inferior
      to surgery. These comparisons, however, are heavily biased by differences in the
      distribution of prognostic factors for which a correction is impossible. Surgery
      alone is clearly not useful in patients presenting with poorly differentiated
      disease or with prostate-specific antigen (PSA) values exceeding 10-20 microg/ml.
      Adjuvant treatment is desirable. Considering the high prevalence of lymph node
      metastases in this group of patients (25-50%), lymphadenectomy is mandatory prior
      to surgery, radiotherapy, or any type of combination treatment.

PMID- 10926085
TI  - Management of locally advanced prostate cancer. 2. Radiotherapy, neoadjuvant
      endocrine treatment, update 1997-1999.
AB  - Part 2 of this review identifies the need for effective adjuvant treatment in
      patients with T3 disease and poor prognostic factors identifiable after surgery.
      A large volume of information has become available from randomized neoadjuvant
      and adjuvant studies using endocrine treatment in association with either surgery
      or radiotherapy. It is well documented that such therapy delays progression in
      prostate cancer of any stage. This must be taken into account in the
      interpretation of adjuvant studies of endocrine treatment. Unfortunately,
      although it leads to volume reduction and downstaging of the primary tumor,
      neoadjuvant endocrine treatment prior to surgery has not been shown to improve
      rates of biochemical or clinical progression and/or survival. Neoadjuvant and
      adjuvant approaches combined with external beam radiotherapy seem to be more
      effective. Recent data show significant improvements in the time to progression
      as well as in disease-specific and overall survival following radiotherapy alone
      as compared with neoadjuvant and/or adjuvant endocrine treatment in addition to
      radiotherapy. At this time, however, it remains unclear whether endocrine
      treatment alone might not produce a similar effect. Studies confirming the value
      of adding radiotherapy to endocrine treatment for T3 disease are urgently needed.

PMID- 10926086
TI  - Contemporary chemotherapeutic approaches for the treatment of hormone-refractory
      prostate carcinoma.
AB  - The medical management of hormone-refractory prostate cancer remains difficult
      and largely palliative. The development of effective antineoplastic agents has
      been frustrated by difficulty in the establishment of satisfactory objective
      response criteria for clinical trials. Nevertheless, recent trials indicate that
      mitoxantrone and spindle toxins such as docetaxel do show activity. Estramustine
      based regimens have also been promising, and such combination regimens are now
      being explored rigorously. Benefiting from new molecular-biologic insights into
      the pathobiology of prostate cancer, novel strategies targeting new molecular
      pathways of cell regulation and cell-cell interaction (such as angiogenesis) are
      also being actively pursued.

PMID- 10926087
TI  - The history of endocrine therapy of benign and malignant diseases of the
      prostate.
AB  - The discovery of endocrine therapy of diseases of the prostate can be regarded as
      one of the most important events in the history of medicine and in urology in
      particular. This article delivers an overview about scientists and clinicians
      involved in this work during the last 200 years. A close historical relation
      between the endocrine therapy of benign prostatic hyperplasia and prostate cancer
      can be recognized. The historical framework between the work of John Hunter in
      the late eighteenth century, that of Charles Brenton Huggins in the late 1930s,
      and that of Andrew Schally in the 1970s has been assembled herein. With respect
      to all the other men who contributed greatly to this medical achievement, e.g.,
      Edward L. Keyes and Russell S. Ferguson, with their first report on
      radioorchiectomy for the treatment of metastatic prostate cancer in 1936, this
      historical vignette is intended to make them part of the historical record.

PMID- 10926088
TI  - Systemic and cavernous plasma levels of endothelin 1 in healthy males during
      different functional conditions of the penis.
AB  - The role of the sympathetic adrenergic nerves in mediating the constant tone of
      penile flaccidity and returning the erect penis to its flaccid state is fairly
      well established. However, it is not yet known whether additional nonadrenergic
      transmitters might be involved in this process. Endothelin 1 (ET-1), a 21-amino
      acid peptide with potent and long-lasting vasoconstrictor activity, may be one of
      the factors contributing to such control. The present study was undertaken to
      determine whether plasma levels of ET-1 changed during flaccidity, tumescence,
      rigidity, and detumescence. We determined plasma levels of ET-1 in the peripheral
      and cavernosal blood of 32 potent adult male volunteers, in whom penile
      tumescence and erection were elicited by exposure to visual and tactile erotic
      stimuli. Whole blood was aspirated from the corpus cavernosum and the cubital
      vein, and ET-1 was quantified in plasma aliquots obtained from the blood samples.
      Using the organ bath technique, we evaluated the contractile effects of ET-1 and
      norepinephrine (NE) on isolated human corpus cavernosum musculature. No
      significant change in ET-1 levels was observed in the peripheral or cavernosal
      blood in the process of developing erection, rigidity, or detumescence. The mean
      plasma level of ET-1 was 0.2-0.7 fmol/ml. In the organ bath, ET-1 elicited
      concentration-dependent contractions of isolated human corpus cavernosum, which
      were much more pronounced than those evoked by the adrenergic agonist NE. Our
      data indicate that despite the in vitro efficacy of ET-1 in stimulating
      contractile activity in isolated human cavernous smooth muscle, the peptide may
      not be of ultimate importance for the mechanism of flaccidity and detumescence in
      healthy males. Nevertheless, the exact role of ETs in the control of penile
      smooth muscle tone remains to be established.

PMID- 10926089
TI  - Ectopic refluxing ureter entering a seminal vesicle cyst associated with
      ipsilateral renal dysplasia.
AB  - The unusual case of a 10-month-old infant with an ectopic refluxing ureter
      entering into a seminal vesical cyst associated with ipsilateral renal dysplasia
      is described. The embryology, differential diagnosis, and therapy are discussed.

PMID- 10926090
TI  - Altered expression of insulin-like growth factor-1 and insulin like growth factor
      binding proteins-2 and 5 in the mouse mutant Hypodactyly (Hd) correlates with
      sites of apoptotic activity.
AB  - Insulin-like growth factor-I (IGF-I) mediated signalling has been implicated to
      be of significant importance during vertebrate embryonic development. IGF-I
      signalling has also been shown to be modulated by a number of IGF binding
      proteins that are thought to act as either agonists or antagonists of IGF
      activity. IGF-I has been implicated in a number of cellular processes, including
      cell division and programmed cell death (apoptosis). We have used the mouse
      mutant Hypodactyly (Hd) as a tool to determine the role of IGF-I and two key IGF
      binding proteins (IGFBP-2 and IGFBP-5) during embryonic development. The Hd
      mutant is a good model with which to study developmental cascades, since it has a
      distinct phenotype in the limb where cellular and molecular circuits have been
      thoroughly investigated. The distinctive pointed limb buds observed in Hd mutant
      embryos have been shown to be the result of a massive increase in apoptosis. We
      show that all three genes, IGF-1, IGFBP-2 and IGFBP-5, display restricted
      expression patterns during limb development. Indeed, IGFBP-5 shows a remarkable
      similarity to the expression of Engrailed-1, which is the vertebrate homologue of
      the Drosophila selector gene Engrailed. We show that there is downregulation in
      the expression of IGFBP-2 in the entire apical ectodermal ridge (AER) in
      homozygous Hd/Hd limb buds, whereas IGFBP-5 is downregulated in specific regions
      in the mutant AER. IGF-I expression is downregulated in Hd limb buds in regions
      undergoing high levels of cell death, consistent with its proposed role as an
      anti-apoptotic factor, while IGFBP-5 is found at higher levels in regions of cell
      death, consistent with reports of its association with apoptosis in adult
      tissues. We propose that these three components of the IGF axis could be involved
      in the manifestation of the mutant phenotype in Hypodactyly, and that this is
      probably a result of their ability to regulate cell survival and cell death.

PMID- 10926091
TI  - The term cell epitope PG-2 is expressed in primordial germ cells and in hypoblast
      cells of the gastrulating rabbit embryo.
AB  - Rapid progress in the functional analysis of germline segregation has been made
      recently using the mouse as an experimental and molecular model. However,
      comparative vertebrate embryology suggests that the time point and mode of
      germline segregation may vary between mammalian species to a greater extent than
      hitherto suspected. Therefore, we started to make use of the monoclonal antibody
      PG-2 specific for primordial germ cells (PGCs) of the rabbit as an opportunity to
      investigate the early phases of germ cell formation in a mammalian species other
      than the mouse. Using immunohistochemistry on whole mount preparations and frozen
      sections we describe the typical mitochondrial labelling of PGCs in the posterior
      part of the primitive streak at 7.0 days post conception (d.p.c.) and the
      subsequent distribution of labelled PGCs at early somite stages (8 d.p.c.) within
      a bilobed area that flanks the posterior margin of the embryo. At these later
      stages, PGCs were found close to, and within, the yolk sac epithelium but they
      were still within the confines of the embryo as defined by the peripheral margin
      in the epiblast/ectoderm layer. Interestingly, cells expressing the PG-2 epitope
      in an atypical, finely granulated intracellular pattern were found in the
      hypoblast layer, but not in the epiblast, at the primitive streak stage. This
      atypical expression pattern may be interpreted as a sign of cells gradually
      losing the PG-2 epitope and this, in turn, may indicate that PGC progenitors are
      allocated to the hypoblast layer before appearing in the mesoderm compartment of
      the primitive streak. These results raise the question as to whether the germline
      in the rabbit is separated during early blastocyst stages, i.e. rather earlier
      than in the mouse.

PMID- 10926092
TI  - Twisted plywood structure of an alternating lamellar pattern in cellular cementum
      of human teeth.
AB  - Human cellular cementum was examined by scanning electron microscopy to elucidate
      the manner of the alternate lamellar pattern forming the cellular cementum.
      Specimens were demineralized, trimmed with a freezing microtome, and treated by
      NaOH-maceration. This procedure was chosen to avoid artifacts in the fibril
      arrangement, and to study the fibrous architecture in detail. For comparison, non
      demineralized, polished and HCl-etched specimens were also prepared. In the NaOH
      macerated specimens, the lamellar pattern of the cellular cementum conformed to
      the twisted plywood principle of bone lamellation with a periodic rotation of
      matrix fibrils resulting in an alternating lamellar pattern. In contrast, matrix
      fibrils were irregularly arranged without indication of rotation of matrix
      fibrils in the polished and etched specimens. Our results suggest that polishing
      and etching procedures cause damage to fibrils and fibril arrangement.

PMID- 10926093
TI  - Expression of major bone extracellular matrix proteins during embryonic
      osteogenesis in rat mandibles.
AB  - It is not known how bone proteins appear in the matrix before and after
      calcification during embryonic osteogenesis. The present study was designed to
      investigate expressions of the five major bone extracellular matrix proteins-
      i.e. type I collagen, osteonectin, osteopontin, bone sialoprotein and osteocalcin
      -during osteogenesis in rat embryonic mandibles immunohistochemically, and their
      involvement in calcification demonstrated by von Kossa staining. Wistar rat
      embryos 14 to 18 days post coitum were used. Osteogenesis was not seen in 14-day
      rat embryonic mandibles. Type I collagen was localized in the uncalcifed bone
      matrix in 15-day mandibles, where no other bone proteins showed immunoreactivity.
      Osteonectin, osteopontin, bone sialoprotein and osteocalcin appeared almost
      simultaneously in the calcified bone matrix of 16-day mandibles and accumulated
      continuously in 18-day mandibles. The present study suggested that type I
      collagen constitutes the basic framework of the bone matrix upon which the
      noncollagenous proteins are oriented to lead to calcification, whereas the
      noncollagenous proteins are deposited simultaneously by osteoblasts and are
      involved in calcification cooperatively.

PMID- 10926094
TI  - Roles of beta-catenin in inner ear development in rat embryos.
AB  - We studied the roles of beta-catenin in inner ear development in rat embryos
      using immunostaining and antisense experiments. High levels of beta-catenin
      appeared transiently in the otic cup during inner ear development. While beta
      catenin accumulation was not yet observed in the thickened surface ectoderm at
      the otic placode, it became to be detected at the apical surface of the otic cup.
      Then it disappeared from the otocyst. When embryos were treated with the beta
      catenin antisense oligodeoxynucleotide (ODN), accumulation of beta-catenin in the
      otic cup was suppressed and the beta-catenin protein level was significantly less
      in treated embryos than in controls. The number of cells in the otic cup in
      treated embryos was smaller than in control embryos. Cells that incorporated
      bromodeoxyuridine (BrdU) in the otic placode were fewer in number in treated
      embryos than in controls. In control embryos, acoustic neurons were detected by
      2H3 (anti-neurofilament 165 kDa antibody) staining within the acoustic neural
      crest complex, while only a little staining of 2H3 was observed in the complex of
      the treated embryos. These results suggested that beta-catenin plays a role in
      cell proliferation in the otic placodes and in differentiation of acoustic
      neurons within the acoustic neural crest complex.

PMID- 10926095
TI  - Lectin cytochemical localisation of glycoconjugates in the olfactory system of
      the lizards Lacerta viridis and Podarcis sicula.
AB  - To investigate the presence of defined carbohydrate moieties on the cell surface
      of the olfactory and vomeronasal receptor cells and the projections of the latter
      into the olfactory bulbs, a lectin binding study was performed on the olfactory
      system of the lizards: Lacerta viridis and Podarcis sicula. Both lizards showed a
      high lectin binding for N-acetyl-glucosamine in the sensory neurons. The lectin
      binding patterns in Lacerta indicated that the main olfactory system possessed a
      moderate density of N-acetyl-galactosamine residues and detectable levels of
      galactose ones. The vomeronasal system on the other hand contained a high density
      of N-acetyl-galactosamine moieties and a moderate density of glucosamine ones. In
      Podarcis the main olfactory system and vomeronasal organ contained respectively
      detectable and moderate levels of galactose residues. The expression of specific
      glycoconjugates may be associated with outgrowth, guidance and fasciculation of
      olfactory and vomeronasal axons.

PMID- 10926096
TI  - Intussusceptive microvascular growth in the lung of larval Xenopus laevis Daudin:
      a light microscope, transmission electron microscope and SEM study of
      microvascular corrosion casts.
AB  - The remodeling of the uniform wide, plexus-like capillary bed of the lung of
      metamorphosing tadpoles of the South African clawed toad Xenopus laevis (Daudin)
      is studied from developmental stages 54 to 65 by scanning electron microscopy
      (SEM) of microvascular corrosion casts (VCCs), light microscopy (LM) and
      transmission electron microscopy (TEM). VCCs reveal that the remodeling of the
      existing uniform, plexus-like lung capillary bed into well-defined alveolar
      capillary meshworks starts in the caudal lung and then gradually proceeds
      cranially. Vascular remodeling is entirely by intussusceptive microvascular
      growth through insertion and enlargement of new and fusion of pre-existing
      capillary meshes. Analyses of lung tissue serial sections at the LM and TEM level
      confirm the presence of intracapillary cushions and tissue posts and correlate
      these structures in respect of size and location to the round to slit-like
      imprints and tiny "holes" found in VCCs. Additionally, SEM of VCCs give clear
      evidence that intussusceptive microvascular growth is also involved in the
      remodeling and maturation of alveolar arterioles and venules.

PMID- 10926097
TI  - Glucose-regulated protein 78 (GRP78) is elevated in embryonic mouse heart and
      induced following hypoglycemic stress.
AB  - This study investigates the distribution and heart levels of glucose regulated
      protein (GRP) 78 during normal development and in response to hypoglycemia in the
      mouse. Results demonstrate that GRP78 is strongly expressed with in the heart,
      neural tube, gut endoderm, somites, and surface ectoderm of mouse embryos during
      early organogenesis, and GRP78 staining remains prominent in the heart from
      gestational days 9.5 through 13.5. Cardiac myocytes are the primary site of GRP78
      expression within the heart. GRP78 levels are highest in the heart during early
      organogenesis and levels decrease significantly by the fetal period. GRP78
      expression is increased after 24 h of hypoglycemia in the early organogenesis
      stage heart. Considering the tissue specific pattern of GRP expression and
      changes during development of the heart, GRPs may play significant roles in the
      normal differentiation and development of cardiac tissue. GRP induction may also
      be involved in hypoglycemia-induced cardiac dysmorphogenesis.

PMID- 10926098
TI  - Restorative surgery of the central nervous system by means of tissue engineering
      using NeuroGel implants.
AB  - A novel approach aimed at restoring tissue structure and function and enhancing
      axonal recovery in damaged parts of the central nervous system is described. In
      contrast to contemporary neurotransplantation technologies which focus on tissue
      reconstruction of neural parenchyma by cell replacement, this approach is based
      on repair by tissue engineering. The technique involves the implantation of a 3
      dimensional polymer hydrogel into the site of injury. The physical properties of
      the hydrogel induce the organisation of migrating wound-healing cells and
      regenerating axons within its 3-dimensional structure. Two complementary
      approaches are described and illustrated using results obtained in vivo and in
      vitro: (1) implantation into the brain and spinal cord of the polymer hydrogel
      NeuroGel, which has a defined macromolecular structure that enhances tissue
      building capabilities, and the implantation of advanced hydrogel derivatives
      carrying biologically active molecules to promote selective cell interactions,
      and (2) biohybrid hydrogels that contain entrapped developing neural tissue
      cells, embryonic carcinoma-derived neurons, or genetically modified cells which
      secrete neurotrophic factors. These techniques create bioartificial tissues with
      neural tissue specificity. The potential of this biomaterial-based approach to
      neural tissue engineering for restorative neurosurgery is discussed.

PMID- 10926099
TI  - Pure lesionectomy versus tailored epilepsy surgery in treatment of cavernous
      malformations presenting with epilepsy.
AB  - Cerebral cavernous malformations (CM) are well-circumscribed vascular
      malformations that often present with epileptic seizures. Although patients may
      initially benefit from antiepileptic drugs, surgical treatment may become
      necessary due to medically intractable seizures. However, it is unclear whether
      lesionectomy alone or tailored epilepsy surgery with previous invasive monitoring
      is the optimal strategy in such cases. We report two patients with epileptic
      seizures due to CM. One patient with few seizures prior to surgery became seizure
      free following resection of the CM and the surrounding tissue. In the second
      patient with long-lasting epilepsy, lesionectomy was performed because of the
      proximity to a functioning left hippocampus. This limited resection failed and
      the patient still had seizures. Subsequently, invasive monitoring with
      intracranial depth and strip electrodes was performed in order to localize the
      epileptogenic area and determine whether the left hippocampus could be spared.
      The invasive study showed the seizure origin in the tissue around the former CM
      but no epileptic discharges in the hippocampus. In a second operation, an
      anterior temporal resection was performed with removal of the epileptogenic
      surrounding tissue and the patient became seizure-free without cognitive
      deficits. The optimal surgical strategy for CM presenting with epileptic seizures
      must take into account various factors such as underlying mechanisms and duration
      of epilepsy, and location of the lesion.

PMID- 10926100
TI  - Temporal lobe epilepsy: a clinicopathological study with special reference to
      temporal neocortical changes.
AB  - The number of patients undergoing surgical treatment for pharmacoresistant
      temporal lobe epilepsy is rapidly increasing. While there have been many
      clinicopathological studies concerning the medial structures of the temporal lobe
      in temporal lobe epilepsy, its lateral structures have received little attention.
      To examine the nature and frequency of lateral temporal lobe abnormalities that
      occur in temporal lobe epilepsy, 22 patients who underwent standard anterior
      temporal lobectomy with hippocampectomy for intractable temporal lobe epilepsy
      were studied. The mean ages at the onset of seizure and at surgery were 15.9
      years and 27.7 years, respectively. The electroclinically determined
      epileptogenic zones were the medial structures of the temporal lobe in 16
      patients and the lateral in six. There was histologic evidence of hippocampal
      sclerosis in 12 of the 16 patients with medial onset seizures and in three of the
      six patients with lateral onset seizures. The lateral structures of the temporal
      lobe showed variable degrees of histological abnormalities in 21 patients. Among
      these abnormalities, heterotopic white matter neurons were observed in six of the
      16 medial patients and in all the lateral patients. Glial changes were also
      common abnormalities, and often glial fibrillary acidic protein (GFAP)-positive
      astrocytes were present over the entire temporal lobe. In addition to hippocampal
      sclerosis, cerebral microdysgenesis and gliosis in the lateral structures of the
      temporal lobe may have a significant role in epileptogenesis of temporal lobe
      epilepsy.

PMID- 10926101
TI  - Sonic detection system for cervical and intracranial vascular disease.
AB  - A sonic analysis system was developed for the detection of cervical and
      intracranial vascular disease (CVD). In this study, sound signals detected
      through the patient's forehead were analyzed using a short-time Fourier
      transformation method, and data were evaluated according to the intensity of
      spectra. A total of 49 patients with CVD and 34 control subjects were studied and
      classified into four grades according to the intensity of the spectra. The true
      positive rate was 83.7% in patients with CVD, and the true negative rate was
      94.1% in the control group. The sensitivity and specificity of this analysis
      system were 83.7% and 5.9%, respectively. The true positive rates for cerebral
      stenosis/occlusion, cerebral aneurysm, and arteriovenous malformation/fistula
      were 85.7%, 73.7%, and 100%, respectively. The future goal is clinical
      application as a mass-screening test for brain disease. This system shows
      potential for this purpose, and further development will continue.

PMID- 10926102
TI  - Brain tissue pO2 related to SjvO2, ICP, and CPP in severe brain injury.
AB  - The aim of this report is to present first experience in comparing the course of
      brain tissue oxygen pressure values (PtiO2) to changes in jugular vein oxygen
      saturation (SjvO2), intracranial pressure (ICP), and cerebral perfusion pressure
      (CPP) after severe brain injury. PtiO2 monitoring was done using a polarographic
      Clark type microcatheter (LICOX pO2 probe) (GMS, Kiel, Germany) with a diameter
      of 0.5 mm and a sensitive area 7.9 mm long inserted in a right frontal position.
      The microcatheter was connected to a LICOX pO2 device. A fiber-optic catheter was
      used to measure SjvO2 and placed into the right internal jugular vein. The ICP
      monitoring was performed with a fiber-optic intraparenchymal device (Camino
      Laboratories, San Diego, Calif.) inserted in a left frontal position. Consistent
      correlations could be noticed between reduced PtiO2 and higher ICP and lower CPP
      levels. However, the absolute value of a single SjvO2 data point seemed to be
      less relevant diagnostically than its trend over a period of time. Owing to their
      experience, the authors suppose that PtiO2 monitoring will be a very important
      and reliable tool in the treatment of brain injury in the future, especially in
      its correlation to ICP and CPP.

PMID- 10926103
TI  - Subependymoma of the lateral ventricles.
AB  - Four subependymomas of the lateral ventricle were reviewed with regard to
      clinical presentation, neuroimaging features, treatment, histopathological
      features, and long-term follow-up. There were two male and two female patients
      ranging in age from 27 to 60 years (mean 48.3 years). While two patients
      presented with symptoms and signs of raised intracranial pressure, two others
      were found incidentally during neuroimaging investigations to have
      intraventricular tumors. Neuroimaging characteristics of these tumors included no
      paraventricular extension, iso- or hypodensity with minimal enhancement on
      computerized tomography (CT), or iso- or hypointensity on T1-weighted and
      hyperintensity on T2-weighted magnetic resonance images (MRI). The usual finding
      on MRI was of no or scarce contrast enhancement, but one case showed
      heterogeneous enhancement. Three patients underwent total resection of the tumor
      and one underwent partial resection. No patients received postoperative radiation
      therapy. All patients have been doing well 4.8 to 15.4 years (mean 8.8 years),
      after surgery. Although there are no absolutely specific features to distinguish
      these tumors from other intraventricular tumors preoperatively, subependymoma
      should be kept in mind for differential diagnosis, as this tumor may safely be
      removed without sacrificing contiguous normal tissue and with good long-term
      results.

PMID- 10926104
TI  - Tuberculosis of the skull. A case report and review of the literature.
AB  - A case of tuberculosis of frontal, ethmoid, and sphenoid bones with intracranial
      extension is presented. The patient had presented with a history of painless left
      frontal swelling for the previous 7 months. A diagnosis of tubercular etiology
      was established with the histopathology of the biopsy specimen. The patient was
      kept on antitubercular treatment for 18 months. She responded well, with a marked
      resolution of symptoms and radiologic findings. At the end of treatment, there
      was no clinical or radiological evidence of disease. At 6-month and 1-year follow
      ups, there was no evidence of recurrence or reactivation of the disease.

PMID- 10926105
TI  - Spinal aspergillosis in nonimmunocompromised host mimicking Pott's paraplegia.
AB  - The aim of this report is to highlight the less-known aspergillus spondylitis
      (AS) that may completely mimic Pott's paraplegia, leading to occasional but
      expensive diagnostic error, as the chemotherapeutic management of the two is
      different. A case of a patient with the diagnosis of Pott's paraplegia who turned
      out to have aspergillus spondylitis is described. Issues and difficulties
      regarding the differentiation between these two forms of spine infection and
      their therapeutic implications are discussed. We conclude that differential
      diagnosis of spinal tuberculosis (TB) should include aspergillus spondylitis, as
      cure of spinal aspergillosis, especially in early stages, is possible with
      surgery and/or antifungal agents, and morbidity and mortality are high in
      neglected cases.

PMID- 10926106
TI  - Lymphocytic adenohypophysitis mimicking a pituitary macroadenoma.
AB  - A 24-year-old woman developed headache and rapidly progressive visual
      disturbances during the last trimester of her first pregnancy. Magnetic resonance
      tomography (MRI) of the brain documented an intra- and suprasellar mass lesion.
      For preservation of vision, transsphenoidal microsurgical decompression was
      performed. Immediately postoperatively, visual acuity improved and hemianopia
      resolved. Histological examination yielded the diagnosis of primary lymphocytic
      adenohypophysitis. This is a rare inflammatory pituitary disease. There are no
      typical clinical, laboratory, or radiological findings that allow precise
      preoperative diagnosis. Even though this autoimmune disorder is principally
      steroid-responsive, an improvement of visual disturbances under steroid therapy
      cannot be predicted. Therefore, surgery is justified not only to establish the
      diagnosis, but also to restore vision by decompression of the optic nerves and
      the chiasm.

PMID- 10926107
TI  - Screening and preventive health practices for the end-stage renal disease
      patient.
AB  - The population of end-stage renal disease (ESRD) patients continues to grow and
      to age. The nephrologist often is the sole or principal physician responsible for
      the total management of these patients. In this role, the nephrologist must
      address issues of routine health maintenance. Screening tests and preventive care
      should be continued to detect, prevent, or minimize comorbid conditions that
      could affect quality of life or survival. Effective primary and secondary
      prevention requires understanding the principles of screening tests and their
      appropriate use. Screening and counseling procedures recommended for healthy
      adults should be continued, although certain screening tests may appropriately be
      discontinued if the expected survival is 5 years or less. Secondary prevention
      for cardiovascular disease is particularly important in ESRD patients, in whom
      accelerated atherosclerosis is often the cause of morbidity and death. Aggressive
      counseling in smoking cessation and in management of hyperlipidemia should be
      undertaken, in the hopes of limiting this common comorbidity.

PMID- 10926108
TI  - The primary care of women with chronic renal disease.
AB  - Nephrologists are often responsible for the primary care of their female patients
      with chronic renal disease. As such, they must be cognizant of medical issues
      that are unique to women. Awareness and implementation of routine health care
      maintenance and cancer screening recommendations are essential. The provision of
      reproductive health services, which includes menstrual history assessment,
      contraception counseling, and services relating to child bearing and sexual
      functioning, is also necessary. Menopausal health concerns and hormone
      replacement therapy are frequently overlooked and need to be addressed. In
      general, the primary care of women with chronic renal disease is similar to that
      of women without renal disease and should adhere to current standards of
      preventive care.

PMID- 10926109
TI  - Cardiac complications of end-stage renal disease.
AB  - Cardiovascular disease is the leading cause of death in patients receiving
      dialysis. This is attributed in part to the shared risk factors of cardiovascular
      disease and end-stage renal disease. The risk factors for coronary artery disease
      include the classic cardiac risk factors of diabetes mellitus, hypertension,
      dyslipidemia, and smoking. Also in this population, hyperparathyroidism,
      hypoalbuminemia, hyperhomocysteinemia, elevated levels of apolipoprotein (a), and
      the type of dialysis membrane may play a role. Management begins with risk factor
      modification and medical therapy including aspirin, beta blockers, angiotensin
      converting enzyme (ACE) inhibitors, and lipid-lowering agents. Revascularization
      is often important, and coronary artery bypass grafting appears to be preferable
      to percutaneous transluminal coronary angioplasty. This is especially true for
      those with multivessel disease, impaired left ventricular function, severe
      symptoms, or ischemia. Congestive heart failure is another common problem in
      dialysis patients. The management includes correction of underlying
      abnormalities, optimal dialysis, and medical therapy. Data obtained from the
      general population indicate obvious benefits from ACE inhibitors and beta
      blockers, and these agents would be considered the therapies of choice.
      Erythropoetin is also an essential component of therapy, but the ideal hemoglobin
      concentration has yet to be determined. Peritoneal dialysis may be helpful in
      severe cases of heart failure. Pericarditis is seen in less than 10% of dialysis
      patients and is best diagnosed by clinical examination and echocardiography.
      Intensive dialysis is often the best initial therapy. Pericardiocentesis is
      reserved for the setting of pericardial tamponade, but a pericardial window is
      more definitive.

PMID- 10926110
TI  - Gastrointestinal and hepatic disorders in end-stage renal disease and renal
      transplant recipients.
AB  - Gastrointestinal and hepatic disorders are commonly associated with end-stage
      renal disease, hemodialysis, and renal transplantation. Recent studies indicate
      that the prevalence of dyspepsia, ulcer disease, and Helicobacter pylori
      gastritis is not significantly different from the general population. Bleeding
      from angiodysplasia, however, is more common in chronic renal failure, as is
      gastroparesis. The prevalence of chronic hepatitis B has been dramatically
      reduced among hemodialysis patients since the advent of universal precautions.
      Response rates to hepatitis B vaccine in noninfected patients, however, are lower
      in these individuals. Chronic hepatitis C is found in 20% to 25% of HD patients
      worldwide and accounts for approximately 1% of all infected individuals. Levels
      of alanine aminotransferase and aspartase aminotransferase are often within
      normal limits but may be elevated compared with a patient's preinfection levels.
      Dialysis has been shown to reduce the level of hepatitis C virus viremia.
      Treatment is similar to non-renal failure patients, although interferon is
      generally not used in renal transplant recipients owing to concerns of graft
      failure.

PMID- 10926111
TI  - Psychiatric considerations in the primary medical care of the patient with renal
      failure.
AB  - The adequate primary care of patients with renal failure, from the choice of the
      modality of treatment down to the everyday answering of questions of patients,
      relatives, and staff, requires a knowledge of the major psychological stresses of
      the illness and the psychiatric complications resulting from these stresses and
      their treatment. Among the major stresses of dialysis are the procedure itself,
      the overall medical treatment which includes medications and diet, and dependency
      independence issues arising from the unique and almost abject dependency of
      patients on a machine, a procedure, and a group of medical professionals. As a
      result of these physical and psychological stresses, the disorders seen include
      delirium, depression, anxiety, suicide, uncooperative behavior, sexual
      dysfunctions, and psychosis. In their treatment, one should first consider what
      prophylactic steps should be taken to avoid their occurrence. It is best that a
      behaviorally trained professional be involved in the initial evaluation of all
      prospective patients. Ideally this should be a consultation-liaison psychiatrist.
      Such involvement may help in the selection of a modality of treatment best suited
      for the psychosocial background of the patient and help identify those most
      susceptible to psychiatric symptoms and disorders. Patients should be told of the
      possibility of complications such as sexual dysfunctions and, in the case of
      dialysis patients, that they may at some point in the course of their treatment
      consider voluntary withdrawal from it. Medications have an important role in the
      treatment of anxiety, insomnia, depression, psychosis, and sexual dysfunctions.
      Concerning the latter, behavioral techniques of Masters and Johnson have been
      found to be useful. Talking therapies seem to be of value for only to a limited
      number of motivated patients.

PMID- 10926112
TI  - Immunizations for pediatric dialysis patients.
AB  - Children maintained on chronic dialysis are at high risk for infection, and
      although the burden of vaccine-preventable disease in this population has not
      been fully documented, primary care of these patients should include careful
      compliance with the routine childhood immunization schedule. There have been
      considerable changes in this schedule in recent years, and an update is provided.
      In addition the supplemental vaccines for pneumococcal and influenza vaccines are
      discussed. Where available, data regarding vaccine response in children on
      dialysis are presented.

PMID- 10926113
TI  - Advanced practice nurses in nephrology.
AB  - With the growing shortage of nephrologists and the increasing number of end-stage
      renal disease patients, collaborative practice arrangements between nephrologists
      and advanced practice nurses (APNs) are becoming more common. This report
      addresses both the credentials and scope of practice of nephrology APNs. Because
      the APN role in nephrology is multifaceted, role responsibilities in the
      nephrology office, chronic dialysis unit, and acute care setting are outlined.
      Nephrologists and APNs have overlapping scopes of practice, and practicing
      collaboratively allows each health care professional to use their strengths
      maximally. Barriers to practice and reimbursement issues are discussed.
      Documentation needed to enter into collaborative practice is delineated. This
      includes collaborative practice agreements, scope of practice statements,
      prescribing protocols, hospital credentialing, and dialysis facility
      credentialing. The goal of the collaborative practice model is to improve
      traditional patient care and delivery of services. The APN's role complements
      that of the nephrologist and offers a unique, holistic approach to the quality of
      patient care that is needed in the current health care environment.

PMID- 10926114
TI  - Patients' perspective of factors affecting modality selection: a National Kidney
      Foundation patient survey.
AB  - The National Kidney Foundation undertook a survey of individuals with chronic
      renal failure to assess factors that may have influenced their treatment
      selection. Areas examined included demographic data, patient education, movement
      between modalities, patient satisfaction with treatment, and sense of well-being.
      The results point to a need for additional patient education and assurance that
      every ESRD patient is informed about all treatment options that are not medically
      contraindicated. There is an additional need for enhanced treatment decision
      making that involves both the patient and the nephrologist. Respondents were
      highly satisfied with their current treatment modality although 17% had
      previously changed treatment owing to personal dissatisfaction. Center
      hemodialysis patients identified staff performance of treatment and dialyzing
      only 3 times weekly as the main advantages of that modality. Those on peritoneal
      dialysis identified its flexibility that allows control over one's personal
      schedule as important. Transplant recipients stressed the importance of living a
      more normal life than that afforded by dialysis. Most respondents expressed a
      positive sense of well-being. While transplant patients expressed a higher sense
      of well-being than individuals on dialysis, it is important to note that
      approximately 70% of those on dialysis reported a positive sense of well-being.

PMID- 10926115
TI  - Dissecting the molecular mechanism of nuclear receptor action: transcription
      coactivators and corepressors.

PMID- 10926116
TI  - Murine pro-tumor necrosis factor expressed in Saccharomyces cerevisiae HF7c
      localizes to membrane/particulate.
AB  - Tumor necrosis factor (TNF) is a cytokine that is produced by immune cells in
      response to bacterial and viral stimuli and plays important roles in various
      inflammatory diseases. TNF is produced as a membrane-bound precursor, which is
      then cleaved to release soluble mature protein. We expressed murine pro-TNF in
      Saccharomyces cerevisiae and examined processing and cellular localization of the
      recombinant protein. Yeast cells were transformed with an expression construct
      carrying the pro-TNF gene under the control of alcohol dehydrogenase promoter.
      Immunoblotting analysis of cell homogenate revealed expression of 26 kD pro-TNF
      in transformed cells. Upon centrifugation, pro-TNF transformed cells fractionated
      into the membrane/particulate. In a clone that expresses a high level of pro-TNF,
      mature 17 kD TNF was detected in the culture medium, although the amount was far
      smaller than that of cell-associated pro-TNF. Flow cytometric analysis of yeast
      spheroplasts demonstrated the presence of TNF on the cell surface. Our results
      show that pro-TNF expressed in yeast mainly resides in the cellular membrane with
      an orientation similar to that of pro-TNF produced in mammalian cells. Our data
      suggest that the transformed yeast cells can be used for the genetic analysis of
      pro-TNF processing machinery in immune cells.

PMID- 10926117
TI  - Major house dust mite allergen, Der p I, activates phospholipase D in human
      peripheral blood mononuclear cells from allergic patients: involvement of protein
      kinase C.
AB  - The major house-dust-mite allergen, Der p I, stimulates the phospholipase D (PLD)
      in peripheral blood mononuclear cells (PBMC) from allergic patients with maximal
      responses after 30 min exposure. At 30 min, Der p I stimulated PLD activity by
      1.4-fold in mild, 1.6-fold in moderate and 2-fold in severe allergic patients
      over control values (p < 0.05). When the cells were pretreated for 24 h with
      phorbol myristate acetate to down-regulate protein kinase C (PKC), PLD
      stimulation by Der p I was largely abolished. These results indicate that in PBMC
      from allergic patients, Der p I can stimulate PLD activity, and that PKC
      activation is involved in this stimulation.

PMID- 10926118
TI  - The mucosal adjuvanticity of two nontoxic mutants of Escherichia coli heat-labile
      enterotoxin varies with immunization routes.
AB  - Escherichia coli heat-labile enterotoxin (LT), which causes a characteristic
      diarrhea in humans and animals, is a strong mucosal immunogen and has powerful
      mucosal adjuvant activity towards coadministered unrelated antigens. Here we
      report the different mucosal adjuvanticity of nontoxic LT derivatives, LTS63Y and
      LTdelta110/112, generated by immunizing through two different mucosal routes.
      Intragastric (IG) immunization with Helicobacter pylori urease alone resulted in
      poor systemic IgG and IgA responses and no detectable local secretory IgA, but IG
      co-immunization with urease and LTdelta110/112 induced high titers of urease
      specific local secretory IgA and systemic IgG and IgA, comparable to those
      induced by wild-type LT. LTS63Y showed far lower adjuvant activity towards urease
      than LTdelta110/112 in IG immunization, but was more active than LTdelta110/112
      in inducing immune responses to urease by intranasal (IN) immunization.
      LTdelta110/112 predominantly enhanced the induction of urease-specific IgG1
      levels following IG immunization, whereas LTS63Y induced high levels of IgG1,
      IgG2a and IgG2b following IN immunization. In addition, quantitative H. pylori
      culture of stomach tissue following challenge with H. pylori demonstrated a 90
      95% reduction (p < 0.0002) in bacterial burden in mice immunized intranasally
      with urease using either mutant LT as an adjuvant. These results indicate that
      the mechanism(s) underlying the adjuvant activities of mutant LTs towards
      coadmnistered H. pylori urease may differ between the IN and IG mucosal
      immunization routes.

PMID- 10926119
TI  - Mutation and expression of the p27KIP1 and p57KIP2 genes in human gastric cancer.
AB  - Cyclin-dependent kinase inhibitors (CDKI) are negative regulators of cell cycle
      progression by binding the cyclin-CDK complex and inhibiting the CDK activity.
      Genetic alteration in the CDKI genes has been implicated for carcinogenesis. To
      test the genetic alteration in the p27 and p57 genes, KIP family CDKI genes, 30
      gastric tumor-normal pairs and 8 gastric cancer cell lines were analyzed for
      mutations by polymerase chain reaction-single strand conformational polymorphism
      (PCR-SSCP). No mutation was detected in these genes although length polymorphisms
      in the proline-alanine repeat of the p57 gene were detected. When the p27 and p57
      mRNAs were analyzed in gastric cancer cell lines by RT-PCR, the p27 mRNA was
      expressed considerably high in tumor cells but expression of the p57 mRNA was
      much low in gastric cancer cell lines compared to that of normal cells. The
      result suggests that inactivation of gene expression rather than mutations in the
      p57 gene accounts possibly for the involvement of this gene in tumorigenesis of
      gastric cancer. However, expression of the p27 gene seems to be essential for
      cell survival.

PMID- 10926121
TI  - Dose-dependent effect of resveratrol on proliferation and apoptosis in
      endothelial and tumor cell cultures.
AB  - Experimental data suggest that Resveratrol, a compound found in grapes and other
      fruits may influence cell proliferation and apoptosis. The aim of our experiments
      was to study the effect of Resveratrol on tumor cell cultures and an endothelial
      cell culture in order to examine the effect of various doses of this compound on
      active cell death and cell proliferation. Human tumor (HT-29, SW-620, HT-1080)
      and endothelial (HUV-EC-C) cells were treated with various doses of (0.1 to 100.0
      microg/ml) Resveratrol in vitro. Cell number, apoptotic and mitotic index was
      measured 24, 48 and 72 h after treatment. Low doses (0.1-1.0 microg/ml) of
      Resveratrol enhance cell proliferation, higher doses (10.0-100.0 microg/ml)
      induce apoptosis and decrease mitotic activity, which is reflected in changes of
      cell number. Resveratrol influences dose dependently the proliferative and
      apoptotic activity of human tumor and endothelial cells. The possible role of
      formaldehyde in the mechanism of action of Resveratrol is discussed.

PMID- 10926120
TI  - Increased levels of multiple forms of dihydrofolate reductase in peripheral blood
      leucocytes of cancer patients receiving haematopoietic colony-stimulating
      factors: interim analysis.
AB  - The precise mechanism whereby granulocytes proliferate when haematopoietic colony
      stimulating factors (CSFs) are used in neutropenic cancer patients is poorly
      understood. The purpose of this study was to investigate whether these cytokines
      bring about leucocyte proliferation by increasing the levels of multiple forms of
      dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer
      patients (25 males and 11 females) with chemotherapy-induced neutropenia. One
      sample of blood from each patient was obtained before therapy either with CSF,
      such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage
      colony stimulating factor (GM-CSF) or with placebo, and another one at the time
      of resolution of neutropenia. Peripheral blood leucocytes in these blood samples
      were counted, separated and lysed. From lysates, cytoplasmic samples were
      prepared and analyzed for active DHFR by a methotrexate-binding assay and for
      total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase
      in total leucocyte count (TLC) was most prominent (P < 0.005) in the CSF group
      and less so (P < 0.05) in the placebo group. The mean +/- SD concentration values
      of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/-
      0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group
      treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein,
      respectively. This increase in active DHFR after stimulation with CSF was
      statistically significant (P < 0.05). Similarly, concentration values of
      immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein
      and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115
      +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after
      stimulation with G-CSF. This increase in concentration of IRE after stimulation
      with GM-CSF or G-CSF was statistically significant (P < 0.005). In the control
      group, there was an increase in the concentration of both active DHFR and IRE
      after treatment with placebo. However, this was not statistically significant.
      Resolution of neutropenia was quicker in the groups treated with CSF compared to
      the control group. Results of this study indicate that colony stimulating factors
      (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of
      multiple forms of DHFR.

PMID- 10926122
TI  - Properties of GST-CALM expressed in E. coli.
AB  - Clathrin-coated vesicles (CCVs) are involved in protein and lipid trafficking
      between intracellular compartments in eukaryotic cells. CCVs are composed of
      clathrin and assembly proteins. The clathrin assembly protein lymphoid myeloid
      leukemia (CALM) gene, encodes a homologoue of the neuronal clathrin assembly
      protein AP180. In this study, we characterized the properties of the CALM
      expressed in E. coli. The molecular weight of bacterially expressed GST-CALM
      fusion protein was approximately 105 kD on SDS-PAGE. The CALM protein could
      promote clathrin triskelia into clathrin cages and could bind the preformed
      clathrin cage. However, 33 kD N-terminal domain of CALM could not bind pre
      assembled clathrin cages, but assemble clathrin triskelia into clathrin cages.
      The CALM protein was bound to SH3 domain through N-terminal domain1, in vitro.
      The CALM protein is proteolyzed by caspase 3, caspase 8 and calpain through C
      terminal domain.

PMID- 10926123
TI  - The effect of question format on measured HIV/AIDS knowledge: detention center
      teens, high school students, and adults.
AB  - This study examines the effect of question format on HIV/AIDS knowledge assessed
      in teens in a detention center, public high school students, and adults. Multiple
      choice items were taken from a Red Cross questionnaire and were transformed into
      open-ended and true/false/don't know formats. Each respondent received an open
      ended and a structured version of the test (consisting of multiple-choice and
      true/false/don't know items). Format effects varied by group and order of
      presentation: High school students and adults performed better on the open-ended
      questions if they had answered the structured versions first-suggesting that the
      structured questions provided these respondents with unintended cues. Detention
      center youths did not benefit from having answered the structured items, and
      scored especially low on the open-ended questions. However, they did almost as
      well as the other groups with the true/false/don't know format. Implications are
      discussed for measuring HIV/AIDS knowledge and evaluating educational programs
      for different target audiences.

PMID- 10926124
TI  - A comparison of the reliability of self-reported drug use and sexual behaviors
      using computer-assisted versus face-to-face interviewing.
AB  - The purpose of this study was to assess the reliability of responses to HIV risk
      behavior questions obtained using a voice-enhanced, computer-administered self
      interview (audio-CASI) system with touch-screen response compared with those
      obtained via face-to-face interviews administered by trained and experienced
      interviewers. Additionally, the study assessed bias that may be attributable to
      an audio-CASI data collection format. The design of the study was a four-group
      crossover design with random assignment to one of four study conditions: (a)
      audio-CASI interview at both intake and retest, (b) face-to-face interview at
      both intake and retest, (c) audio-CASI interview at intake and face-to-face
      interview at retest, and (d) face-to-face interview at intake and audio-CASI
      interview at retest. The study was conducted with a sample of drug users at risk
      for HIV infection interviewed in nonclinical settings. Data were collected at
      intake and 48 hours after intake. Analyses show that data obtained using voice
      enhanced computer interviewing with touch-screen response are reliable and are
      comparable to data obtained using interviewer administered face-to-face
      interviews. However, bias was found to be associated with data collection format
      and may be partially attributable to the complexity of the questionnaire.

PMID- 10926125
TI  - The readability of HIV/AIDS education materials.
AB  - Health care providers use printed materials to educate patients and their
      families about their particular health condition. For the target audience to be
      able to read and understand health brochures, they should be written at or about
      the eighth-grade level and incorporate variables that facilitate comprehension.
      The purpose of this study was to analyze brochures related to HIV/AIDS to
      determine (a) if they were written at a level appropriate for the target audience
      and (b) the extent to which they incorporated variables identified in the
      research literature as facilitating comprehension. The results showed that the
      brochures were written beyond the reading grade level recommended for the target
      audience. Further, although the brochures incorporated a large number of
      variables that facilitate comprehension, many were not used to the extent
      necessary to ensure that readers would be able to read and understand them. The
      results indicated the need for HIV/AIDS-related health brochures to be written in
      such a way that they can be read and understood by the target audience.

PMID- 10926126
TI  - The effect of tailoring a model HIV prevention program for local adolescent
      target audiences.
AB  - In five U.S. sites (Nashville, Tennessee; Newark, New Jersey; northern Virginia;
      Phoenix, Arizona; and Sacramento, California), HIV risk-reduction workshops were
      mounted as a part of the Prevention Marketing Initiative (PMI). In four of the
      five sites, the workshop curriculum was a version of Be Proud! Be Responsible!
      (Jemmott, Jemmott, & McCaffree, 1996) that had been tailored to fit the needs of
      local target audiences. This article describes the evaluation of the PMI
      workshops. Protective effects on several behavioral determinants and behavioral
      outcome measures were observed 1 month after the workshops. Based on the overall
      pattern of results, it was concluded that the PMI workshops reduced the
      likelihood of unprotected sex among participants. The intervention developed by
      Jemmott and colleagues appears to have retained its effectiveness after it was
      tailored to meet perceived local needs.

PMID- 10926127
TI  - The impact of new antiretroviral treatments on college students' intention to use
      a condom with a new sexual partner.
AB  - The aim of this study was to evaluate possible changes in predisposing factors in
      sexual preventive behaviors that could result from the availability of an
      efficient new antiretroviral therapy. A total of 136 young adults were randomly
      assigned a vignette to read describing AIDS as a lethal or chronic disease. After
      reading the vignette, the participants completed a self-administered
      questionnaire assessing the psychosocial determinants of intention to use a
      condom with a new sexual partner. The variables were measured according to
      Ajzen's (1985, 1988, 1991) theory of planned behavior and Triandis's (1977)
      theory of interpersonal behavior. The experimental manipulation was more
      successful when the disease was described as lethal (66 of the 68 subjects)
      rather than chronic (30 of the 68 subjects). For the 96 participants who
      correctly identified the expected outcome of the disease presented in the
      vignette, a significant difference in intention was found between the two
      experimental situations (p < .05). Regression of intention to use condoms on the
      psychosocial variables yielded an adjusted R2 of .62. Perceived behavioral
      control, social norms, personal normative belief and anticipated affective
      reaction were the significant variables explaining this intention. The results
      suggest that intention to use condoms with a new sexual partner is likely to be
      modified by the expected outcome of the disease, that is, whether lethal or
      chronic. Thus, it is suggested that interventions aimed at young adults take into
      account the impacts the new antiretroviral treatments are likely to have on
      preventive behaviors.

PMID- 10926128
TI  - Prenatal HIV prevention practices in a low seroprevalence state.
AB  - The purpose of this study was to build understanding of prenatal HIV counseling
      and testing practices in low seroprevalence states. Responses from a 1998
      population-based survey of Kentucky prenatal care providers (67% response; 312
      analyzed) were compared with findings from patient focus groups. Sixty-two
      percent of clinicians said they routinely counsel prenatal patients with risk
      factors, but only 46% routinely counsel patients without risk factors. The
      proportions routinely offering HIV testing to patients with and without risk
      factors were 94% and 84%, respectively. Prenatal patients identified "fear of a
      positive test result" as the major barrier to test acceptance. This fear was
      fueled by lack of knowledge regarding the benefits of early detection. The study
      concludes that achieving universal prenatal HIV testing will require new
      strategies, such as the distribution of a standardized protocol, that address
      clinicians' concerns about "time burdens" without depriving patients of the
      opportunity to receive individualized counseling.

PMID- 10926129
TI  - Influence of abuse and partner hypermasculinity on the sexual behavior of
      Latinas.
AB  - This study investigated whether abuse and partner hypermasculinity influenced
      sexual behavior change among 46 Latinas (mean age = 34.5 years) who participated
      in an HIV prevention study. After completing a baseline interview, women were
      randomized to either an HIV prevention intervention or a health promotion
      control. Three months later, they took part in follow-up interviews, including an
      assessment of relationship characteristics. The majority (93%) of participants
      reported psychological abuse from their sexual partner during the study period,
      and over two fifths experienced physical abuse. Contrary to expectations, sexual
      behavior change was not related to abuse or partner hypermasculinity. However,
      women in the HIV prevention condition who gave their partner higher
      hypermasculinity ratings reported fewer conversations regarding condoms.
      Moreover, most of the sexual risk reduction observed at follow-up was the result
      of abstinence rather than consistent condom use. The findings provide insight
      into the reality that characterizes the relationships of many Latinas.

PMID- 10926130
TI  - Legal and ethical aspects of vital organ substitution.

PMID- 10926131
TI  - The medical silicones. 1964.

PMID- 10926132
TI  - Plasmapheresis by using secondary membrane filters: twelve years of experience.
AB  - Over 1,600 plasmapheresis procedures have been performed by using secondary on
      line membrane plasma filters in 62 patients over the past 12 years in our
      institution. The disease categories treated include cryoprotein induced diseases
      such as cryoglobulinemia, immune mediated disorders, and familial type II-A
      hypercholesterolemia (FHC). Depending upon the molecular size of the offending
      agent, we used plasma filters (PF) with different pore sizes ranging from 0.02
      microm to 0.04 microm or the cryoglobulin filter (CF) with an average pore size
      of 4.3 microm to remove cryoprecipitable proteins. One plasma volume was
      processed in each treatment. The results of treating 25 patient in over 550
      procedures by using PF show it is safe and effective in treating immune mediated
      disorders and FHC. PF selectively removes macromolecules according to pore size
      and are more specific for the treatment of immune mediated diseases and FHC than
      plasma exchange. The results of treating 37 patients in over 1,100 procedures by
      using CF show it is safe and effective in selectively removing cryoproteins, and
      it is very specific for the treatment of cryoprotein induced diseases. Both PF
      and CF are biocompatible, with no complement activation. Unlike plasma exchange,
      secondary membrane plasma filters do not cause deficiency syndromes and do not
      require albumin or fresh frozen plasma as replacement fluid, making them more
      cost effective than plasma exchange.

PMID- 10926133
TI  - Ex vivo cardiac allograft preservation by continuous perfusion techniques.
AB  - The current technique of cardiac preservation for clinical transplantation by
      infusion of cold cardioplegia and immersion of the heart in an isotonic saline
      bath at 4 degrees C limits safe tissue preservation time to 4 to 6 hours. The
      myriad of benefits to be gained by extending cardiac preservation time has
      prompted the search for alternatives to hypothermic immersion of the heart, the
      most promising of which involves techniques of coronary artery perfusion.
      Countless studies have shown the benefits of long-term storage of donor hearts by
      perfusion rather than the immersion technique. Continuous perfusion preservation
      has three basic advantages over simple immersion. Perfusion preservation with
      oxygen carrying solutions has the advantage of preventing ischemia, anaerobic
      metabolism, and reperfusion injury. Second, nutritional supplementation and
      provision of substrate can be more effectively delivered to myocardial cells.
      Third, continuous perfusion preservation effects the clearance of metabolic waste
      products from the coronary circulation. The composition of the ideal perfusion
      solution and optimal preservation conditions remain incompletely defined.

PMID- 10926134
TI  - Long-term culture of fetal liver cells using a three-dimensional porous polymer
      substrate.
AB  - To develop a bioartificial liver, long-term culture of fetal liver cells over a
      month's time was performed under three different culture conditions, i.e.,
      stationary cultures and shaken-flask cultures, both by using a substratum made of
      porous polyvinyl formal (PVF) resin and conventional monolayer dish cultures as
      controls. Time course changes in cell numbers and albumin secretion were
      evaluated in cultures using Williams' E medium (WE) or minimum essential medium
      alpha (aMEM) supplemented with serum and hormones. In the WE medium, the numbers
      of fetal liver cells in all culture conditions gradually decreased with time, and
      albumin secretion rates rapidly decreased. In the stationary cultures using PVF,
      however, a significant increase in albumin secretion was observed after two weeks
      of culture. When cells were cultured in aMEM, the fetal liver cells exhibited
      sufficient proliferation in stationary and monolayer cultures, although albumin
      secretion rates per single cell were lower than those in WE. On the basis of
      these results, another series of culture experiments were performed, in which
      aMEM was used for the first 10 days to encourage cell proliferation, and the
      medium was changed to WE afterward. In these cultures, albumin secretion rates in
      the stationary cultures dramatically increased after the medium exchanges and
      were maintained at these high levels throughout the remaining culture period.

PMID- 10926135
TI  - Hemoglobin substitute and cardiopulmonary bypass.
AB  - The effects of diaspirin crosslinked hemoglobin (DCLHb, Baxter Health Care Corp.,
      Round Lake, IL) on oxygen exchange in the setting of cardiopulmonary bypass (CPB)
      are unknown. Six calves (71.2 +/- 1.3 kg) were connected to CPB by jugular venous
      and carotid arterial cannulation for 5 hours. Each 1 hour period included 45 min
      of partial CPB (mean flow rate of 50 ml/kg per min) followed by 15 min without
      CPB, at the end of which 500 ml of blood were substituted for with either 500 ml
      of hydroxyethyl starch (Haes; n = 3) or 500 ml of DCLHb (n = 3). A total of 2
      liters of blood was, thus, exchanged (28 ml/kg of blood substitute). Values are
      expressed as mean +/- 1 SD. Analysis of variance for repeated measurements was
      used. The cardiac output (CO) values at 1 h, 3 h, and 5 h were in the Haes group:
      5.7 +/- 2, 6.7 +/- 2.5, and 7.7 +/- 2.5L/min, and in the DCLHb group: 5.7 +/-
      0.6, 4 +/- 1, and 4.7 +/- 1.2 L/min, respectively. The arteriovenous oxygen
      content difference (Ca-Cvo2) values at 1 h, 3 h, and 5 h were in the Haes group:
      4.6 +/- 1, 3.3 +/- 1.5, and 3.5 +/- 1.5 ml/dl, and in the DCLHb group: 4.9 +/-
      0.6, 7.4 +/- 0.7, and 6.6 +/- 0.6 ml/dl, respectively. The oxygen consumption
      (Vo2) values at 1 h, 3 h, and 5 h were in the Haes group: 244 +/- 29, 198 +/- 58,
      and 249 +/- 42 ml/min, and in the DCLHb group: 273 +/- 28, 296 +/- 75, and 306 +/
      65 ml/min, respectively. CO and Ca-Cvo2 showed a significant difference (p <
      0.01), whereas Vo2 did not (p = 0.52). In the DCLHb group of this CPB animal
      model, the cardiac output is lower and the arteriovenous oxygen content
      difference higher than in the Haes group, allowing for preserved oxygen
      consumption.

PMID- 10926136
TI  - Use of a new elastin patch and glue for repair of a major duodenal injury.
AB  - Major duodenal injury with significant tissue loss causes high morbidity and
      mortality. Our new elastin based heterograft combined with small intestinal
      submucosa (SIS) and biodegradable glue could be used for repair of such defects.
      Twenty-four domestic pigs were anesthetized and underwent celiotomy. A 2 cm
      circular defect was created at the second portion of the duodenum with scissors,
      excising one-half of its circumference. Our elastin patch, combined with SIS, was
      applied to cover the defect using biodegradable cyanoacrylate glue and a few
      sutures. It was then covered with omentum. Animals were followed by weight gain,
      endoscopic evaluation, and upper GI barium studies. After 2-5 months, animals
      were sacrificed to obtain specimens. One failed in 3 days due to a technical
      problem, and one failed in 20 days due to an abdominal abscess. The other 22
      animals (22/24, 91.7%) did well, gaining weight. Early endoscopic studies (5-14
      d) showed an intact patch. Upper GI studies showed varying degrees of stenosis at
      the repair site at 3-4 months. Sacrifice after 2-5 months showed complete healing
      of the defect and a dissolved patch. Our new elastin patch material provides a
      reliable barrier for repair of duodenal injury, and the biodegradable glue
      provides quick and easy watertight tissue fusion for our patch.

PMID- 10926137
TI  - Use of a newly developed artificial nerve conduit to assist peripheral nerve
      regeneration across a long gap in dogs.
AB  - There is now considerable evidence that peripheral nerves have the potential to
      regenerate if an appropriate microenvironment is provided. However, there are
      only a few reports of the successful use of artificial nerve conduits to repair
      major nerve defects more than 30 mm in length. In this study, we examined nerve
      regeneration across a long gap in the dog peroneal nerve using a novel artificial
      nerve conduit developed by our group. The conduit consists of a polyglycolic acid
      (PGA) collagen tube filled with laminin coated collagen fibers. In 12 dogs, the
      nerve conduit was implanted across an 80 mm gap in the left peroneal nerve. Three
      months after surgery, compound muscle action potentials (CMAPs) and somatosensory
      evoked potentials (SEPs) were detected. Evaluation of locomotor function revealed
      obvious limping for up to 3 months, but no marked difficulty in walking by 6
      months. Microscopic observation of the regenerated nerve segment at 12 months
      showed numerous myelinated nerve fibers, which were smaller in diameter and
      enclosed in a thinner myelin sheath than normal axons. These results suggest that
      our artificial nerve conduit has potential usefulness in enhancing peripheral
      nerve regeneration, even across large gaps.

PMID- 10926138
TI  - Collagen coated Y-shaped prosthesis for carinal replacement promotes regeneration
      of the tracheal epithelium.
AB  - Carinal reconstruction has the highest operative mortality rate in pulmonary
      surgery, and high tension at the anastomoses is one of the reasons. We have
      reported previously that a new Y-shaped artificial trachea gives acceptable short
      term results. Here, we report our long-term observations and histologic findings.
      A Y-shaped Marlex mesh tube reinforced by a polypropylene spiral was coated with
      collagen, which was extracted from porcine skin, to increase the biocompatibility
      and airtightness of the prosthesis. Replacement of the carina was performed in 20
      beagle dogs. The prosthesis was covered by the omental pedicle in all dogs. Six
      of the 20 dogs survived past 6 months, and 4 were in good condition when they
      were killed. The other 13 dogs died within 11 days of the operation. The main
      cause of death was air leakage from the prosthesis. Bronchoscopic examination of
      the surviving dogs 12 months after surgery revealed that the prosthesis was
      covered with regenerated tissue, and neither stenosis nor dehiscence was
      recognized; 15 months after implantation microscopic examination showed the
      growth of ciliated epithelial cells over the lumen of the prosthesis. These
      results suggest that our Y-shaped artificial trachea might be useful for
      reconstruction of the carina with tissue regrowth, although some improvement of
      the prosthesis is necessary.

PMID- 10926139
TI  - Preclinical evaluation of a hollow fiber silicone membrane oxygenator for
      extracorporeal membrane oxygenator application.
AB  - A silicone membrane hollow fiber oxygenator applicable for use as an
      extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory.
      This silicone hollow fiber displays astonishing mechanical stability, is barely
      compressible or stretchable, and assembles easily while maintaining good gas
      permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This
      study evaluated the gas transfer performances and biocompatibility of the
      oxygenator under ECMO and CPB conditions. In vitro studies that were performed at
      a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35
      +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The
      commercially available Kolobow (Avecor 1500) oxygenator was used as the control,
      and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/-
      2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH)
      was measured according to American Society of Testing and Materials (ASTM)
      standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and
      0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1
      L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2
      transfer rate of the oxygenators were well maintained. This indicates that this
      preclinical silicone membrane hollow fiber oxygenator has superior efficiency,
      less blood trauma, and is smaller when compared with the only clinically
      available Kolobow oxygenator.

PMID- 10926140
TI  - Controlled release from a composite silicone/hydrogel membrane.
AB  - To enhance the drug uptake and release capacity of silicone rubber (SR), N
      isopropylacrylamide (NIPA) hydrogel particles have been incorporated into a SR
      membrane. The NIPA particles were thoroughly blended with uncured SR with a
      certain ratio at room temperature. The mixture was then cast in a Petri dish to 1
      mm thickness and cured 10 hours at 90 degrees C. The SR/NIPA composite gel can
      absorb water approximately equal to its dry weight. Brilliant blue, used as a
      mock drug, was loaded into the composite gel. Drug release increased
      exponentially to a final value that is temperature dependent: low at T> =34
      degrees C, and high at T< 34 degrees C. This finding is because the
      hydrophobicity of NIPA changes with temperature. Pulsed release in response to
      temperature switching between 20 and 39 degrees C has been achieved. Drug uptake
      and release capability strongly depends upon the structure of the composite gel.
      The optimal range of NIPA composition is between 75 and 87% by volume. In the
      cited range, the NIPA particles form an interconnected network that provides a
      channel for diffusion of drug solution. The SR/NIPA composite gel has promising
      attributes as a wound dressing and other uses.

PMID- 10926141
TI  - Low molecular weight protamine: a potent but nontoxic antagonist to heparin/low
      molecular weight protamine.
AB  - To avoid bleeding complications, protamine is routinely used after cardiovascular
      surgery to neutralize the anticoagulant function of heparin. However, its
      clinical use is associated with adverse and sometimes fatal reactions. Based on
      literature review of the mechanism of heparin neutralization and protamine
      induced immunologic toxicity, we propose the following hypothesis: If a chain
      shortened low molecular weight protamine (LMWP) containing the heparin
      neutralizing domain could be derived from native protamine, it could be a potent
      and yet nontoxic heparin antagonist. In this study, we present results to
      validate this hypothesis. LMWP fragments containing an intact arginine sequence
      and an average molecular weight of approximately 1,100 daltons were successfully
      prepared by enzymatic digestion of protamine with thermolysin. In vitro studies
      show that such LMWP fragments completely neutralized the anticoagulant functions
      of heparin and LMWH, based on the anti-Xa chromogenic and aPTT clotting time
      assays. In vivo results reveal that although injection of protamine to mice led
      to obvious production of anti-protamine antibodies, injection of LMWP did not
      elicit any detectable immunogenic responses. In addition, these LMWP fragments
      exhibited a markedly reduced antigenicity and cross-reactivity toward the mice
      anti-protamine antibodies.

PMID- 10926142
TI  - Improved blood compatibility of DLC coated polymeric material.
AB  - There is currently an increasing interest in the use of DLC (diamond like carbon)
      films in biomedical applications. These investigations making use of DLC in the
      biomedical area indicate its attractive properties. In this study, we succeeded
      in depositing DLC on polymer substrates and found the best conditions and method
      for this application. We evaluated the blood compatibility of polycarbonate
      substrates coated by DLC (PC-DLC) under different conditions by using
      epifluorescent video microscopy (EVM) combined with a parallel plate flow
      chamber. Segmented polyurethane (SPU), which has been used to fabricate medical
      devices including an artificial heart, and proven to have acceptable blood
      compatibility, was compared with polycarbonate substrates coated with DLC film.
      The EVM system measured platelet adhesion on the surface of the DLC, by using
      whole human blood containing Mepacrine labeled platelets perfuse at a wall shear
      rate of 100 s(-1) at 1 min intervals for a period of 20 min. PC-DLC demonstrated
      that Tecoflex showed higher complement activation than PC-DLC. There were
      significant differences between the PC-DLC substrates. On the basis of these
      results, it is recommended for use as a coating material in implantable blood
      contacting devices such as artificial hearts, pacemakers, and other devices. This
      DLC seems to be a promising candidate for biomaterials applications and merits
      further investigation.

PMID- 10926143
TI  - Pyrogen retention by the Asahi APS-650 polysulfone dialyzer during in vitro
      dialysis with whole human donor blood.
AB  - The purpose of this study was to test the pyrogen permeability of the new Asahi
      polysulfone APS 650 (APS) dialyzer membrane with a high permeability for middle
      molecules (up to 40 kDa) in comparison with the high-flux Fresenius polysulfone
      F60S (F60S) membrane. Dialyzers were tested in parallel in vitro dialysis
      experiments with whole human donor blood in the blood compartment and
      contaminated bicarbonate dialysate in the dialysate compartment. Dialysate was
      contaminated by a filtrate (0.45 microm) of a Pseudomonas aeruginosa culture in
      bicarbonate dialysate. The production of interleukin-1beta (IL-1beta) and tumor
      necrosis factor alpha (TNFalpha) in whole blood samples taken from the in vitro
      dialysis system was used to detect the passage of cytokine inducing bacterial
      substances derived from P. aeruginosa across the two highflux polysulfone
      membranes. Compared with a sterile control period at the beginning of each
      experiment (n = 5), the TNFalpha inducing activity in the dialysate increased
      from (mean +/- SEM) 42 +/- 12 pg/ml to 1,288 +/- 356 pg/ml with F60S dialyzers
      and from 37 +/- 10 pg/ml to 928 +/- 249 pg/ml with APS dialyzers 30 minutes after
      the dialysate was contaminated. The IL-1beta inducing activity in the dialysate
      increased similarly. In the presence of this significant contamination in the
      dialysate, whole blood circulating in the blood compartments for 60 minutes was
      not stimulated to produce increased amounts of TNFalpha or IL-1beta with neither
      of the two tested membranes. We conclude that F60S and APS membranes are equal in
      their ability to prevent the passage of cytokine inducing bacterial substances
      from highly contaminated dialysate into the patients' blood during hemodialysis.

PMID- 10926144
TI  - Can cytokines be removed by hemofiltration or hemoadsorption?
AB  - To study the removability of pro-inflammatory cytokines by hemofiltration (HF),
      we performed experimental HF with various high-flux membranes (HFM) using a
      closed circuit system filled with monocyte-free human plasma, which contained
      TNFalpha, IL-1beta, and IL-6. Plasma and filtrate samples were taken before and
      1, 2, 3, and 4 hours after the initiation of HF, and each cytokine was determined
      by enzyme-linked immunosorbent assay. IL-1beta was well removed through
      filtration during experimental HF using HFM (PAN>CTA>PMMA>PS). TNFalpha and IL-6
      were only minimally filtered out by HF using HFM. TNFalpha was removed to some
      extent by using PS, and IL-6 was partially removed by using PMMA during
      experimental HF through other mechanisms, such as adsorption, than the
      filtration. IL-1beta and IL-6 were effectively removed by HA using charcoal
      adsorbent column, especially during the first 2 hours, while TNFalpha was only
      partly removed.

PMID- 10926145
TI  - Variation of intra-access flow early and late into hemodialysis.
AB  - Intra-access flow (Qac), measured by ultrasound dilution, is a reliable method
      for screening for access dysfunction. Because of a reduced circulating volume and
      a relative decrease in blood pressure at the end of hemodialysis (HD), we
      hypothesized that Qac could be significantly reduced when measured late into HD.
      Fifty patients were prospectively evaluated for variation in Qac early and late
      into HD. There were 33 native fistulae and 17 synthetic grafts. Six separate
      measures of Qac were performed for each patient by ultrasound dilution (Transonic
      HD01 hemodialysis monitor; Transonic Systems, Inc., Ithaca, NY): three within the
      first 30 minutes and three within the last 30 minutes of HD. Session time was 3.5
      or 4 hours, and mean net ultrafiltration was 3.3 +/- 0.9 L/HD. Early and late
      into HD, mean arterial pressure (MAP) decreased from 100.0 +/- 14.6 to 92.8 +/-
      17.8 mm Hg, heart rate from 73 +/- 11 to 79 +/- 15 bpm, and hematocrit increased
      from 34 +/- 3 to 38 +/- 4%. For the whole group, mean Qac decreased from 1,101.7
      +/- 566.7 to 972.5 +/- 515.6 ml/min (p = NS); when Qac was corrected for a MAP of
      100 mm Hg, the reduction remained nonsignificant (from 1,101.7 to 1,048.0
      ml/min). When considering native and synthetic fistulae separately, the drop in
      Qac was still nonsignificant (from 1,098.9 +/- 613.4 to 983.2 +/- 593.2 for
      native fistulae versus 1,107.2 +/- 480.5 to 999.8 +/- 379.8 ml/min for grafts, p
      = NS). Overall, the percent reduction in Qac early versus late into HD was 11.7%,
      whereas it reached only 4.9% when access flows corrected for MAP were considered.
      We conclude that variation in Qac during HD is relatively small, especially when
      values are corrected for MAP. Therefore, according to our results, Qac measures
      by using the ultrasound dilution method made at any time during HD should be
      reliable for most patients.

PMID- 10926146
TI  - Effects of internal filtration on the solute removal efficiency of a dialyzer.
AB  - To improve solute removal efficiency, several types of dialyzers with enhanced
      internal filtration were introduced for clinical application. In these dialyzers,
      enhanced internal filtration increased convective transport of the solute, in
      addition to diffusive transport. In this study, the effects of internal
      filtration on solute removal efficiency were examined by both analytic and
      experimental studies. Internal filtration is affected by blood (Q(B)) and
      dialysate (Q(D)) flow rates; the patient's hematocrit and plasma level of total
      protein; and the effective length (L(eff)), inner diameter (D), and density ratio
      (DR) of the hollow fibers. An analytic model was introduced for the estimation of
      the changes in mass and momentum along the dialyzer. It clarified the effects of
      these parameters on maximum internal filtration flow rate (Q(IF)) and clearance
      (K) of urea (60 daltons), vitamin B(12) (1,355), and myoglobin (17,000). As a
      result of the analytic study, Q(IF) was increased, resulting in a smaller D, a
      longer L(eff), and a larger DR value. Several types of dialyzers with the same
      cellulose triacetate membrane, produced by Toyobo Co, Ltd., Ohtsu, Japan, and
      Nissho Corporation, Kusatsu, Japan, were used for the experimental study. An in
      vitro evaluation using myoglobin solution showed the same trends as found in the
      analytic study. For example, a dialyzer with 150 microm of D has a 72.0 ml/min
      myoglobin K value, much higher than that of 53.7 ml/min for a dialyzer with 200
      microm of D under constant Q(B) (300 ml/min) and DR (50%) values. Development of
      a dialyzer with enhanced internal filtration, however, should take the patient's
      safety into account, and hemolysis and endotoxin invasion from the dialysate to
      the patient should be avoided.

PMID- 10926147
TI  - Efficacy of a continuous syringe extraction method for monitoring hemodialysis
      ultrafiltrate.
AB  - The evaluation of hemodialysis ultrafiltrate is essential for the assessment of
      uremic toxins, dialyzer net performance, protein catabolic rate, and safety and
      environmental protection. Total dialysate collection (TDC), however, is
      technically far from the daily procedure used. In the present study, use of a
      continuous syringe extraction method (CSEM) as a substitute for TDC was tested to
      determine its comparative effectiveness. Measurements of urea nitrogen,
      creatinine, phosphate, beta2-microglobulin, and albumin were simultaneously
      obtained by both TDC and CSEM in 20 dialysis sessions. CSEM showed an extremely
      significant correlation with TDC for these values. The correlation coefficients
      were >0.97 for these indicators and the value of Fisher's r to z were all <0.001.
      Taken together, these data indicate that CSEM is an effective substitute for TDC.
      With use of CSEM, the evaluation of spent dialysate could become as a daily
      procedure.

PMID- 10926148
TI  - Introduction of a switch that can reverse blood flow direction on-line during
      hemodialysis.
AB  - In several circumstances in hemodialysis, the regular direction of blood flow has
      to be reversed or changed, such as in access dysfunction or insufficient blood
      flow being obtained through the arterial port, as well as to measure actual
      access blood flow in fistulas or grafts by using the formula Qa = Qb((1-R)/R),
      where R represents recirculation in the reversed line configuration. We invented
      a disposable switch device made from standard blood line tubing that can be
      introduced into the dialysis circuit and allows for on-line reversal of lines,
      without needing to manually disconnect and reconnect tubing or interrupt the
      hemodialysis procedure. Over a period of eight months, 16 patients (8
      arteriovenous fistula, 8 PTFE) underwent 193 hemodialysis sessions with the
      switch in place. Circuit pressures, pump, and actual blood flows measured with
      ultrasound dilution were monitored before and after reversing the lines.
      Switching was accomplished within 1-2 seconds. Arterial circuit (r = 0.99),
      venous circuit pressures (r = 0.6), and actual pump flow (364 +/- 56 vs. 350 +/-
      57 ml/min; r = 0.73) correlated very well preswitching and postswitching (p <
      0.0001). Dialysis circuit flow measured with an ultrasound dilution technique
      decreased from 364 +/- 56 (230-480) ml/min preswitching to 350 +/- 57 (220-490)
      ml/min postswitching (p < 0.001). No difficulties or complications were observed.
      This switch device is a useful addition to the technology of hemodialysis in that
      it greatly facilitates the procedure of reversing the lines in an extracorporeal
      circuit while not significantly interfering with circuit pressures and
      connections.

PMID- 10926149
TI  - Kinetics and dose response of the effects of heated glucose peritoneal dialysis
      fluids on the respiratory burst of rat peritoneal leukocytes.
AB  - Heat sterilization of glucose containing peritoneal dialysis (PD) fluids induces
      the production of cytotoxic glucose degradation products (GDPs), some of which
      are still unidentified. The present study was performed to characterize the
      kinetics and the dose-response of the respiratory burst inhibition of GDPs and to
      compare different fluids in this respect. The zymosan-induced respiratory burst
      of rat peritoneal neutrophils and macrophages was measured by chemiluminescence
      (CL) after incubation in vitro for 1, 2, and 4 hours in different homemade and
      commercially available PD fluids, followed by one hour of recovery in Hanks'
      buffer. Heat sterilized fluids were compared with their filter sterilized
      equivalents at two different pH levels. The results revealed that the inhibitory
      effect of heat sterilized fluids on the respiratory burst of peritoneal
      neutrophils is additive to that of low pH, but more fast-acting and, in contrast
      to the pH effect, similar in magnitude to its in vivo equivalent. The effect
      developed within 1 hour and had a linear dose response. The low GDP fluid
      Gambrosol-Bio was less toxic than the conventional fluid Gambrosol, but the
      difference was smaller than expected in relation to measured concentrations of
      known GDPs. Macrophages were less sensitive than neutrophils to the GDP effect.

PMID- 10926150
TI  - Age related skeletal muscle response to electrical stimulation.
AB  - We hypothesized that the conditioned muscles of elderly and growing organisms
      have different responses to electrical stimulation from that of young adult
      organisms. Five day old lambs, 1 year old sheep, and 8 year old elderly sheep
      were used for this investigation. The latissimus dorsi muscle (LDM) was partially
      mobilized and left in situ. Two electrodes were implanted and electrical
      stimulation (ES) was begun for 8 weeks; it was then stopped for 2 weeks. Biopsies
      were taken before ES, after 8 weeks of ES, and after the 2 week delay period. The
      LDM of old sheep has less fatigue resistance than the LDM of younger animals.
      Conditioned LDM of the lamb continued to be fatigue resistant after a 2 week
      delay compared with adult sheep. In all animals, lactate dehydrogenase (LDH)
      fraction five decreased and LDH-1 + 2 fractions increased after ES. After a 2
      week delay, the data returned to baseline values only in adult animals. The
      percentage area occupied by mitochondria in old sheep was less after ES than in
      younger animals. In all animals, the mitochondrial area increased after ES and
      reverted to baseline values after the delay. The number of nuclei and fibers
      considerably increased after ES. Only in the lamb did the number of nuclei and
      fibers continue to be elevated after the delay. There are more changes in young
      skeletal muscle than in adult (1 year or 8 year old) muscle during ES, and they
      "remember" these properties. Elderly skeletal muscle does not convert to a
      fatigue resistant state as completely as adult skeletal muscle during a
      conventional 8 week ES protocol. It is necessary to change and prolong the ES
      protocol for elderly patients.

PMID- 10926151
TI  - Evaluation of a skeletal muscle energy convertor in a chronic animal model.
AB  - A device is under development for powering cardiac assist devices with skeletal
      muscle contracting in a linear configuration by converting muscle work to
      hydraulic energy. Prototype devices are being implanted in goats to study device
      performance and associated muscle mechanics. Percutaneous hydraulic lines provide
      the means to control muscle load and evaluate muscle performance during an
      electrical conditioning protocol. Chronic implant durations ranged from 36 to 87
      days in 7 goats. The latissimus dorsi muscle (LDM) insertion was reconnected to
      the device with a tendon loop. A sternal plate attached with bone screws, and a
      rib clamp secured the device. A new modular sternal mount design was implemented
      to eliminate plate loosening that complicated early implants. Extensive bone
      remodeling around the rib clamp was observed. The tendon attachment demonstrated
      sufficient initial strength; however, in five implants, efforts to repair the
      tendon were required. Device encapsulation was observed, but the device continued
      to cycle freely and no tethering adhesions to the device were found. Interactions
      between the capsule wall and LDM seemed to limit LDM movement in some cases.
      Development of a long-term animal model for energy convertor evaluations is an
      important step toward skeletal muscle powered cardiac assist.

PMID- 10926152
TI  - Numerical studies of blood shear and washing in a continuous flow ventricular
      assist device.
AB  - The third prototype of a continuous flow ventricular assist device (CF3) is being
      developed and tested for implantation in humans. The blood in the pump flows
      through a fully shrouded four bladed impeller (supported by magnetic bearings)
      and through small clearance regions on either side of the impeller. Computational
      fluid dynamics (CFD) solutions for this flow have been obtained by using
      TascFlow, a software package available from AEA Technology, UK. These flow
      solutions have been used to estimate the shear stresses on the blood in the pump
      and, hence, to minimize hemolysis. In addition, the solutions are informative for
      achieving a design that will provide good washing of the blood to minimize the
      possibility of stagnation points that can lead to thrombosis. This study presents
      numerical studies of these phenomena in the CF3. The calculated shear rate
      results are compared with values published in the open literature. The
      comparisons indicate that hemolysis will not be a problem with CF3, which is in
      agreement with preliminary experimental measurements. Flow studies are being
      conducted to determine the optimal size of the clearance regions.

PMID- 10926153
TI  - Miniature circulatory support power transformer.
AB  - Direct power delivery to intracorporeal circulatory support devices risks
      infection. Electrical transformers spanning the integument (skin or mucosa) have
      long been attractive means of circumventing this risk. Yet all existing skin
      surface transformers leak substantial magnetic flux, with an intrinsic risk of
      battery draining cross-coupling by any nearby conductor, requiring strict control
      of surroundings. In a progression of designs, we have used the walls of a small
      pouch, surgically formed from ileum, rather than skin, as a barrier. Previously,
      we reported a torroidal design with complete magnetic circuits, having zero flux
      leakage and unmatched heat dissipation in a 2 week canine trial. This work was in
      three parts: (1) Devices were placed in eight dogs for 9-12 weeks to document
      performance of the existing design. (2) Based on these results, the device was
      further miniaturized. Iterative computational modeling was applied to material
      selection and design. Simultaneously, practical techniques for surgically
      constructing tiny accommodating ileal pouches were explored in cadavers, by using
      polymer "mock-ups" of potential designs. (3) The final design was tested by acute
      implantation in a live 52 kg goat and by in vitro testing of electrical transfer
      function. IN VIVO TRIALS: The earlier design demonstrated 97.2% AC/AC and 84.2%
      DC/DC efficiency with contiguous tissue warming of 0.1 degrees C. DESIGN AND
      PERFORMANCE: A transformer with a Square Permalloy torroidal core (6 cm3, 23
      grams, both coils eight turns) was designed, by using human cadaver trials to
      optimize geometry. Input and output were 6 V, 12W at 9.2 kHz with AC-AC
      efficiency 96%. OPERATIVE PLACEMENT TRIAL: The primary coil easily fit into an
      isolated, vascularized, but otherwise disconnected "blind" ileal pouch < 2 cm
      long with a slender extension to a miniature stoma. With secondary turns, the
      pouch and transformer fit easily into the abdominal wall. This tiny system seems
      compatible with near "forgettable" power delivery allowing unprecedented freedom
      of environment and activity in circulatory support dependent people.

PMID- 10926154
TI  - Results of animal experiments using an undulation pump total artificial heart:
      analysis of 10 day and 19 day survival.
AB  - An undulation pump is a special rotary blood pump in which rotation of a
      brushless DC motor is transformed to an undulating motion by a disc in the pump
      housing attached by means of a special link mechanism. In the blood pump, a
      closed line between the disc and housing moves from the inlet to the outlet by
      this undulating disc motion, which sucks and pushes the blood from the inlet to
      the outlet. Because the same phenomena occurs at both sides of the disc, a
      continuous flow is obtained when the motor rotational speed is constant. The pump
      flow pattern can be easily changed from continuous flow to pulsatile flow by
      controlling the motor drive current pattern. A seal membrane made of segmented
      polyurethane protects the blood from invading the link mechanism as well as the
      motor. UPTAH is fabricated with two undulation pumps and two brushless DC motors.
      Its size is 75 mm in diameter and 80 mm long, and it has one of the great
      advantage of no compliance chamber required in the system. UPTAHs were implanted
      under cardiopulmonary bypass (CPB) into the chest cavities of 16 goats, each
      weighing between 41 and 72 kg. No anticoagulant and antiplatelet agent was used
      after the surgery. The left atrial pressure was automatically controlled to
      prevent its elevation and sucking of the atrial wall into the atrial cuff. The
      following results were obtained: (1) UPTAHs fit well into all the goats; (2) the
      longest survival was 19.8 days, the cause of death was bleeding from the aortic
      anastomosis; (3) No thrombus was observed in the blood pump despite no
      anticoagulant use. Hemolysis depended upon the length of CPB during surgery. When
      CPB time was within 2 hours, hemolysis level returned to baseline within a few
      days of the surgery. UPTAH is a promising implantable TAH, because of its small
      size and easy controllability.

PMID- 10926155
TI  - Polyacrylonitrile membrane interposition between a xenograft and a patient in
      fulminant liver failure: the concept of xenohemodiafiltration in clinical
      practice.
AB  - Fulminant hepatic failure is an important cause of morbidity and mortality in
      intensive care units. Conventional therapies are not sufficiently effective.
      Liver transplantation may be life saving, but a "bridge therapy" is needed until
      transplantation is performed. Hepatic extracorporeal xenohemodiafiltration (XHDF)
      is aimed at the transitory support of a patient with fulminant hepatic failure.
      The first clinical case of XHDF is presented. The system consisted of cross
      circulation between a porcine liver and a patient with fulminant liver failure
      through a polyacrylonitrile membrane. The procedure lasted for 5 hours and
      produced hemodynamic, biochemical, and metabolic improvements. Intracranial
      pressure decreased from 34 to 5 cm H2O, serum ammonia fell from 673 to 370 ng/dl,
      lactic acid from 11 to 5.3 mmol/L, and bilirubin from 7.4 to 2.5 mg/dl.
      Hemodynamic values were maintained stable throughout the procedure. The patient
      was able to undergo transplantation and remains alive 11 months later. XHDF is a
      clinical experimental method that can constitute an alternative clinical therapy
      to support patients with fulminant hepatic failure until an organ is available
      for transplantation.

PMID- 10926156
TI  - Management of a high-output postoperative enterocutaneous fistula with a vacuum
      sealing method and continuous enteral nutrition.
AB  - A postoperative enterocutaneous fistula is one of the most complex medical
      problems. Its treatment may become long-lasting, wearisome, and its outcome often
      is disappointing. Here, we describe the use of a novel device to treat a 67-year
      old patient with a postoperative, high-output enterocutaneous fistula. A
      semipermeable barrier was created over the fistula by vacuum packing a synthetic,
      hydrophobic polymer covered with a self-adherent surgical sheet. To set up the
      system, we constructed a vacuum chamber equipped with precision instruments that
      supplied subatmospheric pressures between 350 and 450 mm Hg. The intestinal
      content was, thus, kept inside the lumen, restoring bowel transit and physiology.
      The fistula output was immediately reduced from a median of 800 ml/day (range,
      400-1,600 ml/day), to a median of 10 ml/day (range, 0-250 ml/day), which was
      readily collected by the apparatus. Oral feeding was reinitiated while both
      parenteral nutrition and octreotide were withdrawn. No septic complications
      occurred, and the perifistular skin stayed protected from irritating intestinal
      effluents. Both the fistula orifice and the wound defect fully healed after 50
      days of treatment. We believe this method may serve as a useful tool to treat
      selected cases of high-output enterocutaneous fistulas without the need for
      octreotide or parenteral nutrition.

PMID- 10926157
TI  - Ontogeny of intestinal nutrient transport.
AB  - Children born prematurely lack the ability to digest and to absorb nutrients at
      rates compatible with their nutritional needs. As a result, total parenteral
      nutrition may need to be given. While this nutritional support may be lifesaving,
      the baby who receives this therapy is exposed to the risks of possible sepsis,
      catheter dysfunction, and liver disease. The rodent model of postnatal
      development provides a useful framework to investigate some of the cellular
      features of human intestinal development. The up-regulation of intestinal gene
      expression and precocious development of intestinal nutrient absorption can be
      achieved by providing growth factor(s) or by modifying the composition of the
      maternal diet during pregnancy and nursing or the weaning diet of the infant.
      Accelerating the digestive and absorptive functions of the intestine would
      thereby allow for the maintenance of infant nutrition through oral food intake,
      and might possibly eliminate the need for, and risks of, total parenteral
      nutrition. Accordingly, this review was undertaken to focus on the adaptive
      processes available to the intestine, to identify what might be the signals for
      and mechanisms of the modified nutrient absorption, and to speculate on
      approaches that need to be studied as means to possibly accelerate the adaptive
      processes in ways which would be beneficial to the newborn young.

PMID- 10926158
TI  - Late gestational changes in sympathomimetic sensitivity in primagravid rabbit
      ligaments.
AB  - The adrenoceptor profile of blood vessels supplying the medial collateral
      ligament (MCL) of virgin and primagravid (day 29 of pregnancy) rabbit knees was
      examined. Topical bolus administration of the alpha1-adrenoceptor agonists
      methoxamine and phenylephrine, and the alpha2-adrenoceptor agonist clonidine, to
      exposed knee joints resulted in a dose-dependent vasoconstriction of ligamentous
      vessels. The rank order of potency for the alpha-agonists was found to be
      phenylephrine > methoxamine > clonidine. Dobutamine, which acts on beta1
      adrenoceptors, and ritodrine, which is a beta2-agonist, imparted a mild
      vasodilatatory effect on MCL blood vessels with the efficacy of ritodrine being
      greater than that of dobutamine. In primagravid rabbits, the constrictor effects
      of methoxamine and phenylephrine were significantly attenuated compared with
      virgin control animals (P < 0.0001), whereas clonidine-mediated vasoconstriction
      was unaltered in the gravid animal (P = 0.3957). With respect to beta
      adrenoceptor activity, the dilatational effect of dobutamine was the same as in
      controls (P = 0.5294), while ritodrine vasoactivity was completely abolished in
      primagravid knees (P < 0.005). These findings suggest that the adrenergic control
      of rabbit MCL blood flow is predominantly mediated by postjunctional alpha1 and
      beta2-adrenoceptors. Pregnancy leads to either downregulation and (or)
      desensitisation of alpha1 and beta2-adrenoceptors in the ligament which could
      disrupt normal joint homeostasis.

PMID- 10926159
TI  - A role for calcitonin gene-related peptide in rabbit knee joint ligament healing.
AB  - Knee joint ligament healing has been shown to be improved when the torn ligament
      ends remain in contact, however, the rationale for these effects is unknown. The
      sensory neuropeptide calcitonin gene related peptide (CGRP) has potent trophic
      and vasodilatatory properties and as such is thought to be advantageous in wound
      repair. In ascertaining a role for CGRP in rabbit medial collateral ligament
      healing, the present study examined changes in CGRP-like immunoreactivity (CGRP
      LI) and CGRP-mediated vasomotor responses in gap injured (non-contact), Z-plasty
      apposed (contact), and sham operated control medial collateral ligaments. At 6
      weeks post-trauma, CGRP-LI decreased in the healing zone of gap injured and Z
      plasty apposed medial collateral ligaments compared with controls, and non
      contact ligament nerve fibres exhibited an abnormal morphology. Topical
      administration of CGRP (10(-13) to 10(-9) mol) caused a dose-dependent increase
      in ligament perfusion in each experimental group of knees. The CGRP-mediated
      vasodilatation associated with gap injured ligaments was not significantly
      different from controls (P = 0.06), whereas apposed medial collateral ligaments
      showed an augmented response to the peptide (P < 0.0005). These findings indicate
      that the beneficial effects of ligament interposition post-trauma may be related
      to an enhanced responsiveness to CGRP in conjunction with a more typical re
      innervation profile. Conversely, the aberrant characteristics of CGRP-LI nerves
      occurring in gap injured tissue is suggestive of impaired CGRP release which may
      explain the poor functional recovery associated with these ligaments.

PMID- 10926160
TI  - Prolonged exercise following diuretic-induced hypohydration: effects on
      cardiovascular and thermal strain.
AB  - To examine the role of a reduction in plasma volume (PV) on the cardiovascular
      and thermoregulatory responses to submaximal exercise, ten untrained males (VO2
      peak = 3.96 +/- 0.14 L x min(-1); mean +/- SE) performed 60 min of cycle exercise
      at -61% of VO2 peak while on a diuretic (DIU) and under control (CON) conditions.
      Participants consumed either Novotriamazide (100 mg triameterene + 50 mg
      hydrochlorothiazide, a diuretic) or a placebo, in random order, for 4 days prior
      to the exercise. Diuretic resulted in a calculated 14.6% reduction (P < 0.05) in
      resting PV. Heart rate was higher (P < 0.05) at rest and throughout exercise for
      DIU compared with CON. No differences were observed for cardiac output (Qc) and
      stroke volume (SV) at rest for the two conditions, but during exercise both Qc
      and SV were lower (P < 0.05) with DIU. Exercise VO2 (L x min(-1)) for CON and DIU
      at 30 min (2.39 +/- 0.09 vs 2.43 +/- 0.08) and 60 min (2.56 +/- 0.08 vs 2.53 +/-
      0.12) were similar between conditions. Whole body a-vO2 difference was
      significantly greater (P < 0.05) for DIU both at rest and during exercise as
      compared with CON. Rectal temperature (Tre) was significantly higher (P < 0.05)
      during DIU from 15 min to the end of exercise. Blood concentrations of
      norepinephrine were higher (P < 0.05) with DIU compared to CON at 15 min of
      exercise and beyond. For blood epinephrine, no differences were observed between
      DIU and CON. These results suggest that reductions in PV led to greater
      circulating concentrations of norepinephrine which likely resulted from increased
      cardiac and thermoregulatory stresses. In addition, reductions in PV do not
      appear to increase cardiovascular instability during prolonged dynamic exercise.

PMID- 10926161
TI  - Effect of dietary cardiac glycosides on blood pressure regulation in rats.
AB  - To investigate the possible physiological significance of dietary cardiac
      glycosides in blood pressure regulation, the blood pressure of normal Sprague
      Dawley rats raised on a regular diet, which naturally contains large amounts of
      Na+-pump inhibitors, was compared with that of rats on a purified synthetic diet,
      which contains no Na+-pump specific inhibitors, and with that of rats on a
      synthetic diet supplemented with 10 microg x mL(-1) ouabain or 10 microg x mL-
      convallatoxin in the drinking water. After 6 weeks on the synthetic diet, the
      systolic blood pressure in the synthetic diet group was significantly elevated
      (145 +/- 5 vs. 128 +/- 4 mmHg, P < 0.05). At 10 weeks it reached a plateau (154
      +/- 3 vs. 122 +/- 3 mmHg, P < 0.05). Plasma renin activity and Na+ level were
      significantly higher in animals fed synthetic diets than in the regular diet
      group (P < 0.01). Administration of either losartan or lisinopril or a switch to
      a low salt synthetic diet (0.03% sodium) normalized the synthetic diet-induced
      high blood pressure. Supplementation of the synthetic diet with the cardiac
      glycosides delayed the onset of the increase in blood pressure for 4 weeks.
      Plasma aldosterone levels were approximately doubled in the cardiac glycoside
      treated groups. Higher plasma Na+ levels and hematocrit values present in the
      synthetic diet group were normalized by the glycoside supplements. These results
      suggest that supplemental dietary cardiac glycosides exert bidirectional effects
      on blood pressure regulation through actions that modulate extracellular fluid
      and electrolyte balance.

PMID- 10926162
TI  - Skeletal and heart muscle protein turnover during long-term exposure to high
      environmental temperatures in young rats.
AB  - A study was undertaken to determine the long-term effects of a hot environment on
      protein turnover in skeletal and cardiac muscles of young homeothermic animals.
      Three groups of 36 male 28 day old rats were housed at 35 degrees C (hot group),
      25 degrees C (control group), or 25 degrees C but pair-fed to the intake of the
      hot group (pair-fed group). Rates of protein synthesis and degradation were
      measured in vivo on days 5, 10, 15, and 20. By day 20, soleus and gastrocnemius
      (skeletal muscle) protein masses were 7 and 14% lower in the hot group and 31 and
      21% lower in the pair-fed group compared with the control group (P < 0.05). The
      fractional rate of protein synthesis (k(syn)) was on average 11% lower (P < 0.05)
      in the hot group compared with control rats and was not different from pair-fed
      rats. The fractional rate of skeletal muscle protein degradation (k(deg)) in hot
      rats was slightly lower than in control rats; k(deg) was on average 18% higher (P
      < 0.05) in the pair-fed group compared with the hot group and this difference
      appeared to be most prominent on day 5. In heart, by day 20, protein mass was 30%
      lower in the hot group and 40% lower in the pair-fed group compared with control
      rats (P < 0.05). k(syn) was on average 19% lower (P < 0.05) in the hot group
      compared with the control group, but not different from pair-fed rats. In the
      heart there were no differences in k(deg) among treatments. Plasma
      triiodothyronine (T3) concentration was lower in the hot group, but not in the
      pair-fed group, compared with controls. In conclusion, chronic exposure to hot
      environments was associated with lower skeletal and cardiac muscle mass and
      protein turnover; lower protein mass in this tissue was due to decreased k(syn);
      this is consistent with lower plasma T3 concentrations. In pair-fed rats, k(syn)
      was also reduced, but interestingly k(deg) was not, resulting in a greater loss
      of skeletal muscle mass. These results suggest that heat exposure invokes
      physiological adaptations to preserve skeletal muscle mass despite decreased food
      intake. In the heart, loss of protein was a result of decreased k(syn), which can
      be primarily ascribed to lower food intake.

PMID- 10926163
TI  - Plasma homocysteine is decreased in the hypothyroid rat.
AB  - Recent clinical studies have indicated that plasma homocysteine was significantly
      increased in hypothyroid patients. Since hyperhomocysteinemia is an independent
      risk factor for cardiovascular disease we investigated homocysteine metabolism in
      hypothyroid rats. Hypothyroidism was induced in one study by addition of
      propylthiouracil (PTU) to the drinking water for 2 weeks. In a second study,
      thyroidectomized and sham-operated rats were used with thyroid hormone
      replacement via mini-osmotic pumps. Unlike the human hypothyroid patients, both
      groups of hypothyroid rats exhibited decreased total plasma homocysteine (30% in
      PTU rats, 50% in thyroidectomized rats) versus their respective controls. Thyroid
      replacement normalised homocysteine levels in the thyroidectomized rat. Increased
      activities of the hepatic trans-sulfuration enzymes were found in both models of
      hypothyroidism. These results provide a possible explanation for the decreased
      plasma homocysteine concentrations. The hypothyroid rat cannot be used as a model
      to study homocysteine metabolism in hypothyroid patients.

PMID- 10926164
TI  - Effect of maternal nutrient restriction in early to mid gestation and
      thyrotrophin-releasing hormone on lamb survival following Caesarean section
      delivery near to term.
AB  - We investigated the influence of restricted maternal nutrition between 28 and 77
      days gestation on survival and thermoregulatory adaptation following Caesarean
      section delivery near to term. This study was designed to examine the hypothesis
      that adaptation after birth would be compromised in those lambs born to nutrient
      restricted ewes. We further hypothesised that this would be due in part to
      inadequate hypothalamic-pituitary-thyroidal function. Lambs born to nutrient
      restricted ewes were untreated (RU) or treated with thyrotrophin-releasing
      hormone (TRH; RT) immediately prior to umbilical cord clamping. Single bearing
      ewes consumed either 6.60 MJ x day(-1) (controls, n = 4) or 3.00 MJ x day(-1)
      (nutrient restricted, n = 15) from 28-77 days gestation, after which all ewes
      consumed 7.20 MJ x day(-1). All lambs born to control ewes commenced continuous
      breathing and began to shiver following Caesarean section delivery and survived
      to 6 h after birth. Only 4 out of 9 RU lambs established continuous breathing and
      survived to 6 h after birth compared with all RT lambs. Six hours after birth, RT
      lambs possessed perirenal brown adipose tissue with a higher thermogenic activity
      than 6 h old RU or control lambs. Lamb birth weight was similar in all groups. In
      conclusion, near-term lambs born to ewes nutrient restricted in early to mid
      gestation are at increased risk of death following Caesarean section delivery.
      Survival after birth can be significantly enhanced if TRH is administered to the
      lambs immediately before delivery.

PMID- 10926165
TI  - Use of recombinant human ferrochelatase as a sensitive bioassay for N
      alkylprotoporphyrin IX formed after interaction of porphyrinogenic xenobiotics
      with rat liver microsomes.
AB  - Several porphyrinogenic xenobiotics elicit mechanism-based inactivation of
      cytochrome P450 (CYP) isozymes, leading to the formation of N-alkylprotoporphyrin
      IX (N-alkylPP), a potent inhibitor of ferrochelatase, the terminal enzyme in heme
      biosynthesis. Recognizing their role in experimental porphyria, our long term
      objective is the establishment of an appropriate in vitro system for the
      detection and quantification of N-alkylPPs, formed in human liver after the
      administration of potential porphyrinogenic compounds. In a previous study, we
      used a combination of thin-layer chromatography and UV-visible spectrophotometry
      to isolate and identify N-alkylPPs after incubating porphyrinogenic compounds
      with rat liver microsomes. However, the overall yield of N-alkylPPs was low, and
      it was concluded that in vitro systems, such as human lymphoblastoid microsomal
      preparations containing single cDNA-expressed human cytochrome P450 (CYP)
      isozymes, do not contain sufficient CYP for in vitro studies designed to isolate
      N-alkylPP. In the present study we demonstrate that purified recombinant human
      ferrochelatase (FC) provides an extremely sensitive bioassay system for N
      alkylPPs and is capable of detecting N-alkylPP in the 10(-6) nmol range.
      Therefore, we propose that this bioassay system might allow the use of human
      lymphoblastoid microsomal preparations containing single cDNA-expressed human CYP
      isozymes to detect N-alkylPP produced after mechanism-based (catalysis-based) CYP
      inactivation. If this is found to be correct it will facilitate identification of
      potentially porphyrinogenic drugs prior to administration to humans.

PMID- 10926166
TI  - Identification of a respiratory related area in the rat insular cortex.
AB  - The aim of this study was to map areas within the rat insular cortex from which
      respiratory responses originate and compare those sites with gastrointestinal
      control regions. The insular cortex was systematically microstimulated and
      histological location of responsive sites determined. Increased inspiratory
      airflow and decreased respiratory cycle duration were considered to be
      respiratory excitatory responses. The responses were localized in dysgranular and
      agranular insular cortex at levels caudal to the joining of the anterior
      commissure. More rostrally, respiratory inhibitory responses were elicited: these
      were manifested as a decrease in inspiratory airflow without a significant
      alteration in respiratory cycle duration. Respiratory inhibitory responses were
      usually accompanied by changes in gastric motility. These results suggest that
      the respiratory area in the rat insular cortex consist of two distinct zones
      which overlap a region modulating the gastrointestinal activity.

PMID- 10926167
TI  - Cellular and molecular mediators in common pathway mechanisms of chronic renal
      disease progression.
AB  - Injury mechanisms activated by the hemodynamic adaptations to nephron loss are
      considered to represent a final common pathway that underlies the progressive
      nature of chronic renal disease. In this article, we review experimental evidence
      that the induction of cell adhesion molecule, cytokine and profibrotic growth
      factor gene expression and the resultant renal infiltration by inflammatory
      cells, especially macrophages, are important components of these common pathway
      mechanisms. Interventions aimed at inhibiting these mechanisms may offer new
      treatments for slowing or arresting the progression of chronic renal disease.

PMID- 10926168
TI  - Epithelial calcium channel: gate-keeper of active calcium reabsorption.
AB  - The epithelial calcium channel present in the apical membrane of 1,25
      dihydroxyvitamin D3-responsive nephron segments represents the first member of a
      new family of calcium channels. This review covers the distinctive properties of
      this highly calcium-selective channel and highlights the implications for our
      understanding of the process of calcium reabsorption.

PMID- 10926169
TI  - The role of calbindin and 1,25dihydroxyvitamin D3 in the kidney.
AB  - The identification of a putative apical Ca++ channel in 1,25dihydroxyvitamin D3
      responsive epithelia (proximal intestine and the distal nephron) as well as
      recent studies using calbindin-D28k knock-out mice indicating the first direct in
      vivo evidence for a role for this calcium-binding protein in renal calcium
      absorption suggest mechanisms, which had remained incomplete, related to the
      control of renal calcium absorption.

PMID- 10926170
TI  - Renal cell-urinary crystal interactions.
AB  - Crystals of calcium oxalate and calcium phosphate bind to anionic molecules on
      the apical surface of renal collecting duct cells. Atomic arrays on crystal faces
      interact stereospecifically with cell-surface anions to bind crystals that
      nucleate in tubular fluid, or those that nucleate directly on the plasma
      membrane. The internalization of adherent crystals, changes in gene expression,
      and secretion of specific proteins ensue, and appear to be important processes in
      crystal retention and kidney stone pathogenesis.

PMID- 10926171
TI  - Parathyroid hormone-related peptide and Indian hedgehog.
AB  - Normal endochondral bone development requires temporal and spatial coordination
      of various cell types. Parathyroid hormone-related peptide and Indian hedgehog
      interact with each other and form a feedback loop that plays a major role in this
      coordination. Defects in the signalling of either of the two molecules cause
      severe bone malformations.

PMID- 10926172
TI  - Is aplastic osteodystrophy a disease of malnutrition?
AB  - Adynamic bone disease is emerging as a major type of renal osteodystrophy in
      chronic dialysis patients. Relative hypoparathyroidism is one of the important
      abnormalities underlying this disease. Recently, several reports have suggested
      that hypoparathyroidism reflects, at least in part, a state of malnutrition and
      contributes to the poor prognosis of patients on hemodialysis and chronic
      ambulatory peritoneal dialysis. Such a risk of survival may result not only from
      the malnutritional state, but also from unknown mechanisms resulting from
      parathyroid hormone (PTH) deficiency, or from other abnormalities that suppress
      PTH secretion. Another major abnormality underlying adynamic bone disease is the
      skeletal resistance to PTH in patients with uremia. Owing to the recent research
      on bone turnover at the molecular level, several new mechanisms for this
      abnormality have been elucidated. Correction of this 'skeletal resistance to PTH'
      will lead to the optimal management of parathyroid function and bone turnover in
      the future.

PMID- 10926173
TI  - The effects of acid on bone.
AB  - Metabolic acidosis induces calcium efflux from bone and in the process buffers
      the additional hydrogen ions. Initially metabolic acidosis stimulates
      physicochemical mineral dissolution and then cell-mediated bone resorption.
      Acidosis increases activity of the bone resorbing cells, the osteoclasts, and
      decreases activity of the bone forming cells, the osteoblasts. Osteoblastic
      immediate early response genes are inhibited as are genes controlling matrix
      formation.

PMID- 10926174
TI  - A better understanding of the kidney in health and disease: what will it take?

PMID- 10926175
TI  - The pathogenesis of autosomal dominant polycystic kidney disease: an update.
AB  - The identification of PKD1 and PKD2, the two major genes responsible for
      autosomal dominant polycystic kidney disease, are the seminal discoveries upon
      which much of the current investigation into the pathogenesis of this common
      heritable disease is based. A major mechanistic insight was achieved with the
      discovery that autosomal dominant polycystic kidney disease occurs by a two-hit
      mechanism requiring somatic inactivation of the normal allele in individual
      polarized epithelial cells. Most recent advances are focused on the function of
      the respective protein products, polycystin-1 and polycystin-2. Indirect evidence
      supports an interaction between polycystin-1 and -2, albeit it is unlikely that
      they work in concert in all tissues and at all times. They associate in yeast two
      hybrid and cotransfection assays and there is a striking similarity in the renal
      and pancreatic cystic phenotypes of Pkd2-/- and Pkd1del34/del34 mice. Also, the
      respective homologues of both proteins are expressed in the same sensory neuronal
      cells in the nematode and the human disease phenotypes remain completely
      overlapping with the major difference being in relative severity. Mounting
      evidence supports the hypothesis that polycystin-1 is a cell surface receptor. A
      close homologue in the sea urchin sperm mediates the acrosome reaction in
      response to contact with egg-jelly, the nematode homologue functions in mechano-
      or chemosensation, and the solution structure of the repeated extracellular
      polycystic kidney disease domains reveals a beta-sandwich fold commonly found in
      surface receptor molecules. Indirect evidence also supports the initial
      hypothesis that polycystin-2 is a calcium channel subunit. Several closely
      related homologues retain the calcium channel signature motif but differ in their
      predicted interaction domains, and one of these homologues has been shown to be a
      calcium regulated cation channel. Several important distinctions in polcystin-1
      and -2 function have also been discovered. Polycystin-2 has a role in cardiac
      development that polcystin-1 does not. High level polycystin-2 expression in
      renal epithelial cells coincides with maturation and elongation of tubules and,
      unlike polycystin-1, persists into adulthood. In cells in tissue culture,
      polycystin-2 is expressed exclusively in the endoplasmic reticulum whilst the
      cellular expression of polycystin-1 remains unknown. Overall, the difficult task
      of understanding the autosomal dominant polycystic disease process is proceeding
      apace.

PMID- 10926176
TI  - Hepatocyte growth factor in renal regeneration, renal disease and potential
      therapeutics.
AB  - Hepatocyte growth factor (HGF) has mitogenic, motogenic, morphogenic, and anti
      apoptotic activities on renal cells and is a potential renotropin for renal
      protection and repair. In chronic renal failure/fibrosis, HGF in the kidney
      declines in a reciprocal manner to the increase in transforming growth factor
      beta (TGF-beta). Neutralization of HGF by the antibody leads to acceleration of
      renal failure/fibrosis while HGF administration leads to remarkable attenuation,
      thus indicating the importance of HGF versus TGF-beta counterbalance in both
      pathogenesis and therapeutics in cases of chronic renal failure. HGF is being
      strongly considered for potential treatment of acute and chronic renal failure.

PMID- 10926177
TI  - Theoretical basis and clinical evidence for differential effects of angiotensin
      converting enzyme inhibitors and angiotensin II receptor subtype 1 blockers.
AB  - Drugs that block the renin-angiotensin system have multiple mechanisms of action
      that may be beneficial in stabilizing or delaying progression of renal disease.
      The most important of these actions is the simultaneous control of both systemic
      and glomerular capillary hypertension. Angiotensin-converting enzyme (ACE)
      inhibitors are a class of drugs that have proven antihypertensive and
      antiproteinuric effects, with a demonstrated ability to delay progression of
      renal disease in conjunction with the ability to reduce systemic blood pressure.
      The mechanism of action for these drugs remains poorly described, but depends in
      part on an ability to reduce plasma angiotensin II levels and increase plasma
      bradykinin levels. Angiotensin II receptor subtype 1 (AT1) blockers differ in
      their mechanism of action from the ACE inhibitors. These drugs primarily block
      the binding of angiotensin II to its type 1 site. In so blocking the type 1
      binding site, however, greater levels of circulating angiotensin II result, and
      the resultant biologic activity of angiotensin II or its metabolites such as
      angiotensin(1-7) and angiotensin(3-8) may be more directed to other angiotensin
      binding sites. AT1 blockers have similar antihypertensive and antiproteinuric
      effects to those of ACE inhibitors and they may prove to be as useful as ACE
      inhibitors in delaying progression of renal disease. Because ACE inhibitors and
      AT1 blockers inhibit the renin-angiotensin system by different mechanisms, there
      is a possibility that combining them in clinical practice may prove efficacious
      for lowering blood pressure and for providing target organ protection.

PMID- 10926178
TI  - Fibrosis and angiogenesis.
AB  - Research during the past few years has contributed vastly to a better
      understanding of fibrosis and angiogenesis. Although studies to understand the
      molecular processes associated with fibrosis and angiogenesis were performed
      independently of each other, some common parallels have emerged. Translation of
      these observations into potential therapeutic possibilities needs further
      exploration.

PMID- 10926179
TI  - Fetal origins of adult hypertension: a renal mechanism?
AB  - It is well-recognized that the etiology of cardiovascular disease includes at
      least two components: a genetic component and a 'lifestyle' or environmental
      component. However, epidemiological evidence accumulating over the past decade
      has provided an increasingly strong case for the important involvement of a third
      component, that of environmental conditions during development (i.e. before
      birth), in contributing to an individual's overall cardiovascular risk. Factors
      in the prenatal environment to which a baby is exposed can cause permanent
      changes in the structure and function of specific tissues in the body. Although
      perhaps valuable in the short term in that they allow survival until birth, these
      changes are maladaptive in the long term because they predispose the individual
      to an array of adult diseases. Experimental data elucidating the possible
      physiological and morphological mechanisms by which this perinatal 'programming'
      for adult cardiovascular disease occurs are only just now becoming available.
      However, it appears that the renin-angiotensin system, and the important role it
      plays in renal development, may be central in setting the trajectory that leads
      to cardiovascular disease, and in particular hypertension.

PMID- 10926180
TI  - Cell biology and molecular mechanisms of injury in ischemic acute renal failure.
AB  - The pathogenesis of acute renal failure has been attributed to persistent
      vasoconstriction and leukocyte-endothelial interactions, resulting in
      inflammation and compromise of local blood flow to the outer medulla, the loss of
      tubular epithelial cell polarity with multiple functional sequelae, necrosis or
      apoptosis of epithelial cells, and the de-differentiation, migration and
      proliferation of surviving cells. In this paper, the authors present their views
      of pathophysiology of ischemic acute renal failure.

PMID- 10926182
TI  - Bibliography. Current world literature. Mineral metabolism.

PMID- 10926181
TI  - Renal tubular effects of endothelin-B receptor signaling: its role in
      cardiovascular homeostasis and extracellular volume regulation.
AB  - The role of the endothelin-B receptor in vascular homeostasis is controversial
      because the receptor has both pressor and depressor effects in vivo. One
      potential depressor mechanism of endothelin-B activation is through the promotion
      of natriuresis and diuresis in the renal tubule. Recent studies demonstrate that
      rodents genetically deficient for the endothelin-B exhibit sodium-dependent
      hypertension due to an absence of tonic inhibition of the epithelial sodium
      channel in the distal nephron. These studies suggest that the predominant role of
      endothelin-B receptors in the basal physiologic state may be to regulate renal
      sodium excretion relative to the level of oral salt intake.

PMID- 10926183
TI  - Bibliography. Current world literature. Renal pathophysiology.

PMID- 10926184
TI  - Web and PACS: heralding the new age of imaging in the health care community.

PMID- 10926185
TI  - Update on digital image management and PACS.
AB  - Information technology is becoming a vital component of all health care
      enterprises, from managed care services to large hospital networks, that provides
      the basis of electronic patient records and hospital-wide information. The
      rationale behind such systems is deceptively simple: physicians want to sit down
      at a single workstation and call up all information, both clinical data and
      medical images, concerning a given patient. Picture archiving and communication
      systems (PACS) are responsible for solving the problem of acquiring,
      transmitting, and displaying radiologic images. The major benefit of PACS resides
      in its ability to communicate images and reports to referring physicians in a
      timely and reliable fashion. With the changes in economics and the shift toward
      managed and capitated care, the teleradiology component of PACS is rapidly
      gaining momentum. In allowing remote coverage of multiple sites by the same
      radiologists and remote consultations and expert opinion, teleradiology is in
      many instances the only option to maintain economically viable radiologic
      settings. The technical evolution toward more integrated systems and the shift
      toward Web-based technology is rapidly merging the two concepts of PACS and
      teleradiology in global image management and communication systems.

PMID- 10926186
TI  - Data and image processing for abdominal imaging.
AB  - Modern imaging techniques allow information from within the human body to be
      obtained by using noninvasive or minimally invasive means. This article is
      intended as a summary of the tools used for processing and displaying such
      datasets, with a focus on abdominal imaging. Although these tools and their
      applications are permanently evolving, their use for clinic and research is
      already recognized as essential. As an insight into the near future, advanced
      protocols such as multidimensional and multimodality diagnostic and therapy
      planning are also demonstrated with a few clinical examples.

PMID- 10926187
TI  - Virtual colonoscopy and colorectal cancer screening.
AB  - Colorectal cancer (CRC) is the leading cause of cancer related death in the
      United States. Virtual colonoscopy is a new method for imaging the colon and has
      produced promising early results for polyp and cancer detection. The challenge
      remains to reproduce these favorable results in clinical practice and to evaluate
      the use of virtual colonoscopy in a purely screening population. Virtual
      colonoscopy may dramatically improve population participation in screening
      programs and play a major role in minimizing the impact of CRC.

PMID- 10926188
TI  - Value of barium studies for predicting primary versus secondary non-Hodgkin's
      gastrointestinal lymphoma.
AB  - BACKGROUND: To determine the predictive value of a single lesion versus
      multifocal disease for differentiating primary and secondary gastrointestinal
      (GI) lymphoma on barium studies. METHODS: Our study group consisted of 90 cases
      of non-Hodgkin's GI lymphoma from the radiologic archives of the Armed Forces
      Institute of Pathology in which barium studies had been performed. Each of those
      studies was reviewed jointly by two of the authors to determine in a blinded
      fashion whether the patients had a single lesion or multifocal disease (defined
      as two or more discrete lesions). Medical and pathologic records were then
      reviewed to determine whether these patients had primary (defined as lymphoma
      arising in the GI tract) or secondary (defined as disseminated lymphoma with
      associated GI tract involvement) GI lymphoma. The final clinical diagnosis was
      then correlated with the radiographic findings to test the hypothesis that a
      single lesion is more likely to be associated with primary GI lymphoma and that
      multifocal disease is more likely to be associated with secondary GI lymphoma.
      RESULTS: Sixty-eight patients had a single lesion in the GI tract on barium
      studies; 52 (76%) of these patients had primary GI lymphoma and 16 (24%) had
      secondary GI lymphoma. Another 22 patients had multifocal disease on barium
      studies; 20 (91%) of these patients had secondary GI lymphoma and two (9%) had
      primary GI lymphoma. CONCLUSION: The predictive value of a single lesion for
      primary GI lymphoma on barium studies was 76%, and the predictive value of
      multifocal disease for secondary GI lymphoma was 91%. Thus, our data suggest that
      it is often possible to differentiate these two forms of GI lymphoma on the basis
      of the radiographic findings.

PMID- 10926190
TI  - Gastrointestinal hemorrhage in hepatocellular carcinoma: management with
      transheptic arterioembolization.
AB  - Gastrointestinal hemorrhage in patients with hepatocellular carcinoma is common
      and a major contributor to mortality. These patients tend to have a very poor
      prognosis. This report describes five such cases in which gastrointestinal
      bleeding was one of the presenting problems and required urgent management. The
      causes of massive intermittent gastrointestinal bleeding were variceal (two
      cases), direct invasion of the duodenum (one case), transverse colon (one case),
      and stomach (one case). All five patients were inoperable because of locally
      advanced disease, poor general condition, or comorbid disorders and were managed
      with angioembolization. After transcatheter embolization, the bleeding stopped
      completely in two patients and was reduced significantly in the remaining three.
      We report the role of transhepatic arterioembolization in the management of
      gastrointestinal bleed in such patients, and we recommend its use more often in
      similar situations.

PMID- 10926189
TI  - Perforation of the alimentary tract: evaluation with computed tomography.
AB  - BACKGROUND: To assess the value of computed tomography (CT) in the diagnosis of
      perforation of the alimentary tract (AT). METHODS: During a 4-year period 76
      patients with proven AT perforation underwent CT within 1 week before surgery or
      endoscopy. We retrospectively reviewed these CT scans to determine the signs of
      AT perforation. There were 41 men and 35 women (28-90 years old). Our goal was to
      establish the diagnosis of AT perforation and, if this was possible, to identify
      the site and cause of the AT wall rupture. The CT diagnosis of perforation was
      based on (a) direct findings of extraluminar air or gastrografin and (b) indirect
      findings of an abscess or an inflammatory mass surrounding an enterolith in the
      region of appendix or a bowel wall-related phlegmon or abscess with fluid in the
      mesentery or surrounding radiopaque foreign body. RESULTS: There were 65 true
      positive and 11 false-negative cases. Levels of perforation were the esophagus
      (two), stomach (five), duodenum (12), small bowel (15), appendix (six), and colon
      (36). Causes were peptic ulcer (11), foreign body (five), trauma (seven),
      iatrogenic (nine), appendicitis (six), diverticulitis (21), Crohn disease (five),
      AT carcinoma (eight), and ischemia (four). Level and cause were correctly
      predicted in 55 and 51 instances, respectively. The sensitivity was estimated to
      85.5%. CONCLUSION: CT is a valuable method in the diagnosis of AT perforation.
      The diagnosis can be established rapidly, without patient preparation and with a
      high sensitivity.

PMID- 10926191
TI  - Cavernous transformation of the portal vein secondary to tumor thrombosis of
      hepatocellular carcinoma: spiral CT visualization of the collateral vessels.
AB  - BACKGROUND: We investigated the constituting collateral vessels in cavernous
      transformation of the portal vein (CTPV) caused by tumor thrombosis of
      hepatocellular carcinoma (HCC) by using contrast-enhanced spiral computed
      tomographic (CT) examination. METHODS: Fifty-four histopathologically proven HCC
      patients with tumor thrombosis-induced CTPV were retrospectively included and
      assigned to cirrhosis negative (n = 31) and positive (n = 23) groups. Another 15
      cirrhotic patients with portal hypertension but no HCC and CTPV were used for
      comparison. Standardized dual-phase contrast-enhanced spiral CT was performed for
      all patients. CT appearances of the collateral vessels of CTPV were observed, and
      their visualization rates were analyzed. RESULTS: Biliary (cystic and
      paracholedochal veins) and gastric (left and right gastric veins) branches of the
      portal vein were the most frequently visualized collateral vessels of CTPV. There
      was a marked difference in CT visualization rates for biliary branches between
      patients with and without CTPV (83-94% vs. 0). No difference existed in
      visualization rates for gastric branches across the three groups (77-87% for left
      gastric, 58-61% for right gastric vein). CONCLUSIONS: Biliary and gastric
      branches of the portal vein are the major collateral vessels of CTPV. The
      intergroup differences in CT visualization rates may provide clues to the roles
      that they might play in the hemodynamic adaptation process of CTPV.

PMID- 10926192
TI  - Adult right-sided Bochdalek hernia facilitated by coexistent hepatic hypoplasia.
AB  - An adult case of right-sided Bochdalek hernia complicating intrathoracic
      intestinal strangulation is presented. Formation of this rare right-sided
      diaphragmatic hernia was facilitated by coexistent hypoplasia of the medial
      segment of left hepatic lobe. Computed tomography showed characteristic findings
      such as dilated small intestine with convergence of mesenteric folds in the
      thorax, which was highly diagnostic of intestinal strangulation due to
      diaphragmatic hernia.

PMID- 10926193
TI  - Chilaiditi syndrome: sonographic findings.
AB  - BACKGROUND AND METHODS: Sonographic (US) findings of Chilaiditi syndrome have
      been rarely reported in the literature. We reviewed 18 cases of Chilaiditi
      syndrome to pinpoint its US pattern. RESULTS: (1) US showed gas echoes of
      different sizes superimposed over the entire liver in two cases and over the
      right hepatic lobe in six cases, leading to a high suspicion of Chilaiditi
      syndrome. (2) US showed a small gas echo in the hepatodiaphragmatic space,
      mimicking pneumoperitoneum in eight cases. In this instance, altering the
      patient's position allowed for confirmation of the lack of a change in the
      location of the gas echo, unlike cases of pneumoperitoneum. (3) The hepatic
      surface appeared as a hyperechoic mass in two cases. CONCLUSION: Knowledge of US
      patterns of Chilaiditi syndrome helps avoid confusion with pneumoperitoneum or
      hepatic masses.

PMID- 10926194
TI  - Fascioliasis: US, CT, and MRI findings with new observations.
AB  - BACKGROUND: The purpose of this study is to describe the ultrasonographic (US),
      computed tomographic (CT), and magnetic resonance imaging (MRI) findings in
      fascioliasis and to emphasize the impact of radiology in diagnosis. METHODS:
      Radiologic findings in 23 consecutive patients with fascioliasis were
      prospectively recorded. All patients had at least one US and CT examination, and
      10 of them were studied by MRI. All diagnoses were confirmed by serologic
      methods. In the first three cases, initial diagnosis was reached by microscopic
      demonstration of the parasites' eggs in bile obtained by US-guided gallbladder
      aspiration. RESULTS: In the hepatic phase of fascioliasis, multiple, confluent,
      linear, tractlike, hypodense, nonenhancing hepatic lesions were detected by CT.
      On US, the parasites could be clearly identified in the gallbladder or common
      bile duct as floating and nonshadowing echogenic particles. MRI showed the
      lesions as hypo- or isointense on T1-weighted images and as hyperintense on T2
      weighted images. CONCLUSIONS: CT findings in the hepatic phase and US findings in
      the biliary phase are characteristic of fascioliasis. Because clinical and
      laboratory findings of fascioliasis may easily be confused with several diseases,
      radiologists should be familiar with the specific radiologic findings of the
      disease to shorten the usual long-lasting diagnostic process.

PMID- 10926195
TI  - Gadopentetate dimeglumine as an oral negative gastrointestinal contrast agent for
      MRCP.
AB  - BACKGROUND: We investigated the feasibility of using intravenous magnetic
      resonance (MR) contrast agent as a gastrointestinal oral negative contrast agent
      to null the bowel signal during MR cholangiopancreatography (MRCP). METHODS: In
      the first part of the study, a phantom study was performed to select the optimal
      concentration of MR contrast agent to be used as an oral negative contrast agent
      in MRCP. In the second part of the study, 23 consecutive patients suffering from
      different pancreaticobiliary diseases were imaged with a single-shot fast spin
      echo pulse sequence. The data acquisition was started without oral contrast agent
      and then repeated with oral contrast agent. From the MR images taken with and
      without oral contrast agent, the gallbladder, cystic duct, common bile duct, and
      pancreatic duct were assessed and graded by two radiologists. RESULTS: The oral
      contrast agent was tolerated well by all patients. In all patients the high
      signal intensity from the intestinal fluid was completely suppressed. The
      depictions of the gallbladder and cystic duct were slightly and moderately
      improved, respectively, whereas the depictions of the common bile duct and
      pancreatic duct were markedly improved by the oral contrast agent administration.
      CONCLUSION: Diluted intravenous MR contrast agent can be an effective and safe
      oral negative contrast agent in eliminating signal intensity of the
      gastrointestinal tract, thus improving the depiction of the biliary system in
      MRCP.

PMID- 10926196
TI  - Atypical exocrine and endocrine pancreatic tumors (anaplastic, small cell, and
      giant cell types): CT and pathologic features in 14 patients.
AB  - BACKGROUND: Our purpose was to review a series of 14 patients with atypical
      exocrine and endocrine pancreatic tumors to derive characteristic computed
      tomographic and pathologic features that might allow better diagnosis,
      categorization, and management of these patients. METHODS: Medical records from
      several university medical centers were reviewed retrospectively. RESULTS: We
      identified three separate types of pancreatic tumors that had substantially
      different morphologic and prognostic features. Among these rare tumors,
      anaplastic carcinoma was the most common (nine of 14 cases), and these tumors
      were large, partly necrotic, locally invasive, and invariably metastatic (lymph
      nodes and/or liver) at the time of diagnosis. Three patients with poorly
      differentiated (small cell) carcinoma had a confluent pancreatic mass and
      lymphadenopathy but no ductal obstruction, closely resembling lymphoma or
      metastatic disease. Two patients with giant cell (osteoclastlike) carcinoma had a
      large, encapsulated multicystic tumor with hemorrhage, and these tumors were
      resectable for cure. CONCLUSION: Although a specific diagnosis may not be
      possible in some cases, we believe that knowledge of certain pathologic and
      computed tomographic features should lead to optimal diagnosis, therapy, and
      prognosis.

PMID- 10926197
TI  - Adenosquamous carcinoma of the pancreas: report of two cases.
AB  - Adenosquamous carcinoma (ASqC) of the pancreas is a rare tumor. We analyzed the
      radiologic findings and clinical manifestations in two such cases. In both cases
      (a 51-year-old woman and a 67-year-old man), the portal system was selectively
      and largely invaded, the superior mesenteric vein in one and the splenic vein in
      the other, without arterial invasion. Thus, peripancreatic vessels should be
      carefully observed in patients with ASqC of the pancreas. One case showed an
      unusual mode of spread. Only a huge metastatic lesion was initially detected,
      leading to the misdiagnosis of primary malignant mesenteric tumor. Such an
      unusual growth pattern is also worth noting.

PMID- 10926198
TI  - Imaging evaluation of renal trauma.
AB  - The kidney is the most commonly injured genitourinary organ. The diagnosis and
      treatment depend on the mechanism of injury (blunt or penetrating trauma), the
      clinical presentation, and the extent of the lesions. Knowledge of the different
      appearances of the posttraumatic kidney on imaging studies is essential for
      prompt and effective treatment of patients. This pictorial essay reviews the
      imaging evaluation and principal imaging findings associated with blunt and
      penetrating renal trauma. The role of computed tomography is emphasized because
      it is a very sensitive, specific, and accurate modality in detecting the presence
      or absence of injury and defining its extent.

PMID- 10926199
TI  - Spontaneous rupture of adrenal myelolipoma: spiral CT appearance.
AB  - We report the helical computed tomographic findings of a symptomatic giant (11
      cm) adrenal myelolipoma with spontaneous extracapsular hemorrhage. Narrow
      collimation (3 mm) imaging and three-dimensional reconstructions were useful to
      fully characterize the components and location of the lesion. A literature search
      showed a striking male and right-sided predominance for spontaneously hemorrhagic
      myelolipomas.

PMID- 10926200
TI  - Complications after laparoscopic gynecologic procedures: CT findings.
AB  - Laparoscopic gynecologic surgery has gained worldwide popularity in the past few
      years, but complications of this new technique do occur. We encountered three
      patients who developed major complications after laparoscopic gynecologic
      procedures including perforation of the sigmoid colon, urinary bladder, and
      ureter. We report the computed tomographic findings of these cases and the
      diagnostic dilemmas they posed.

PMID- 10926201
TI  - Complications of hip arthroplasty simulating pelvic or bladder pathology:
      sonographic and radiographic findings.
AB  - BACKGROUND: The purpose of this paper was to describe the imaging features of
      intrapelvic complications of total hip arthroplasty. METHODS: The clinical
      presentation, ultrasound, and radiographic findings of three cases were reviewed.
      RESULTS: Intrapelvic extrusion of cement or medial migration of prosthetic
      hardware caused extrinsic compression of the bladder. CONCLUSION: Intrapelvic
      complications due to the mechanical effects of total hip arthroplasty are rare
      but may simulate intrinsic pelvic or bladder pathology on sonography. Plain
      radiographs and contrast studies provide clues to the correct diagnosis.

PMID- 10926202
TI  - Retroperitoneal bronchogenic cyst: CT and MR imaging.
AB  - Retroperitoneal bronchogenic cysts are extremely rare congenital anomalies that
      represent malformations of the embryonic foregut and are morphologically
      expressed as maldevelopments of the respiratory system. Because of the low
      prevalence of these tumors, their imaging features have seldom been described. We
      present the computed tomographic and magnetic resonance imaging findings of a
      case of retroperitoneal bronchogenic cyst.

PMID- 10926203
TI  - Selective induction of the monocyte-attracting chemokines MCP-1 and IP-10 in
      vesicular stomatitis virus-infected human monocytes.
AB  - It is characteristic of viral infections that monocytes/macrophages and
      lymphocytes infiltrate infected tissue, and neutrophils are absent. CC and non
      ELR CXC chemokines predominantly attract mononuclear leukocytes, whereas the ELR
      motif-expressing CXC chemokines primarily act on neutrophils. To investigate the
      general role of chemokines in viral diseases, we determined their release and
      expression patterns after infection of human monocytes with vesicular stomatitis
      virus (VSV). Human monocytes were productively infected by VSV. Surprisingly, VSV
      did not induce the release of the proinflammatory cytokines tumor necrosis factor
      alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. In contrast, we found
      a strong induction of the CC chemokine monocyte chemotactic protein-1 (MCP-1) and
      the non-ELR CXC chemokine interferon-gamma (IFN-gamma) inducible protein-10 (IP
      10) by VSV on the gene and protein level. The expression and release of the
      neutrophil chemoattractants IL-8 and growth-related oncogene-alpha (GRO-alpha)
      remained unaffected after VSV infection. Our results indicate that the typical
      monocyte and lymphocyte-dominated leukocyte infiltration of virus-infected tissue
      is based on a selective induction of mononuclear leukocyte-attracting chemokines.

PMID- 10926204
TI  - An indoleamine 2,3-dioxygenase-negative mutant is defective in stat1 DNA binding:
      differential response to IFN-gamma and IFN-alpha.
AB  - We have previously reported the isolation of mutant cell lines from the human
      carcinoma line ME180 that are resistant to the antiproliferative effect of
      interferon-gamma (IFN-gamma). These cell lines were defective in the induction of
      indoleamine 2,3-dioxygenase (IDO), a key enzyme of tryptophan catabolism. One of
      these cell lines, 3B6A, was chosen for further study. This cell line was also
      defective in the ability of IFN-gamma to protect against vesicular stomatitis
      virus (VSV) infection. However it maintained a normal antiviral response to IFN
      alpha. A promoter-chloramphenicol acetyltransferase (CAT) construct containing
      the promoter region of IDO, which includes IFN-gamma activation site (GAS), IFN
      stimulated response element-1 (ISRE-1), and ISRE-2 regions, was not expressed in
      3B6A in the presence of IFN-gamma, indicating that the defect was likely to be in
      either Stat1 or IFN regulatory factor-1 (IRF-1), transcription factors known to
      bind to these cis-acting sequences. The induction of other IFN-gamma-inducible
      genes, such as tryptophanyl-tRNA synthetase (hWRS), was also affected.
      Electrophoretic mobility shift assays (EMSA) comparing nuclear extracts from
      parental and mutant cells indicated that Stat1 from the mutant did not bind to
      GAS sequences. However, Western blot analysis indicated that Stat1 protein was
      present. This IDO-negative phenotype can be reversed by transfection with a Stat1
      expression vector. DNA sequencing of the Stat1 cDNA from wild-type and 3B6A cells
      indicated that an amino acid change occurred in the Stat1 protein of the mutant
      at W573, a tryptophan conserved in all known Stat proteins. We hypothesize that a
      change in this region of the Stat protein affects the response to IFN-gamma but
      not to IFN-alpha.

PMID- 10926205
TI  - An unusual adverse effect of interferon: hypertrichosis of the eyelashes.
AB  - Hypertrichosis of the eyelashes is a rare adverse effect of interferon-alpha
      treatment. We present a 21-year-old man with chronic renal failure and hepatitis
      B virus (HBV) infection who developed hypertrichosis of the eyelashes as a
      complication of IFN-alpha therapy. The patient was a candidate for living related
      renal transplantation and was given IFN-alpha 15 million units per week for HBV
      DNA positivity. After 6 months of therapy, HBV DNA positivity persisted, and the
      dose of IFN was increased to 30 million units per week. At the end of the first
      half of the second 6 months of therapy, the patient suffered from bilateral
      hypertrichosis of the eyelashes.

PMID- 10926206
TI  - Characterization of RNABP, an RNA binding protein that associates with RNase L.
AB  - The 2',5'-oligoadenylate (2-5A)/RNase L pathway is one of several enzymatic
      pathways induced by interferons (IFN). RNase L is a latent endoribonuclease that
      is activated on its binding by 2-5A and inhibited by the ribonuclease L inhibitor
      (RLI). We have shown previously by coimmunoprecipitation that RNase L may be
      associated with a 90-kDa RNA binding protein (RNABP), identified with a
      monoclonal antibody (mAb) raised against an RNase L complex purified under native
      conditions on 2-5A-sepharose. Here we confirm, by gel-filtration and pull-down
      analysis, the association of RNase L and RNABP, and we demonstrate that this
      association is significantly increased in the presence of 2-5A. Moreover, we
      found that RNABP protein levels decrease during terminal differentiation in
      various cell lines but do not vary during vesicular stomatitis virus (VSV) or
      encephalomyocarditis virus (EMCV) infection or following IFN-alpha/beta
      treatment. In this latter case, although total cellular RNABP levels do not vary,
      the amount of RNABP found in the cytoplasm increases in comparison to that found
      in the nucleus, indicating a cytoplasmic localization of RNABP after IFN
      alpha/beta treatment. Finally, we demonstrate the interaction between RNase L and
      RNABP in intact cells. Microinjection of an mAb against RNABP into HeLa cells
      inhibits RNase L antiviral activity and partially inhibits the IFN-alpha/beta
      induced antiviral activity.

PMID- 10926207
TI  - IFN-gamma enhances osteoclast generation in cultures of peripheral blood from
      osteopetrotic patients and normalizes superoxide production.
AB  - Interferon-gamma (IFN-gamma) treatment increases osteoclastic bone resorption in
      vivo in patients with malignant osteopetrosis (OP). The treatment effect was
      studied in vitro in osteoclasts generated by culturing peripheral white blood
      cells (PWBC) from OP patients and normal human control subjects. Osteoclasts were
      treated with or without IFN-gamma prior to the end of the culture period.
      Osteoclasts from normal subjects were large in size (161 +/- 18 microm in
      diameter) with >10 nuclei per osteoclast. These cells showed intense staining for
      tartrate-resistant acid phosphatase (TRAP), expressed abundant calcitonin
      receptors (CTR), and formed numerous resorption pits on bovine bone slices,
      indicative of authentic osteoclasts. In contrast, similarly cultured osteoclasts
      from OP patients were smaller in size (18 +/- 3 microm in diameter), with 2-3
      nuclei per osteoclast, and stained lightly for TRAP. However, IFN-gamma treatment
      of osteoclasts from OP patients resulted in the formation of larger osteoclasts
      (171 +/- 33 microm in diameter) with >10 nuclei per cell, similar in appearance
      to osteoclasts from normal subjects. IFN-gamma stimulation increased the
      intensity of TRAP staining (p < 0.0001) to levels near that of the normal
      osteoclasts. Unstimulated osteoclasts from 6 OP patients had a significantly
      lower baseline level of superoxide production, as measured by nitroblue
      tetrazolium reduction (p < 0.0001), compared with normal osteoclasts. IFN-gamma
      markedly increased (p < 0.0001) superoxide production. Whereas there was a 3-fold
      increase in superoxide generation in OP patients' osteoclasts, osteoclasts from
      control subjects had only a small and insignificant increase in superoxide
      production after IFN-gamma treatment.

PMID- 10926208
TI  - Effect of deficiency of the double-stranded RNA-dependent protein kinase, PKR, on
      antiviral resistance in the presence or absence of ribonuclease L: HSV-1
      replication is particularly sensitive to deficiency of the major IFN-mediated
      enzymes.
AB  - Control of viral replication by interferon (IFN) is thought to be principally
      mediated by the 2',5'-oligoadenylate synthetase (OAS)/RNAse L, double-stranded
      dependent protein kinase (PKR), and myxovirus resistance protein (Mx) pathways.
      In this study, we monitored the constitutive and IFN-induced antiviral activity
      in mouse embryo fibroblasts lines derived from mice with targeted disruption of
      either PKR or PKR/RNAse L genes. At high multiplicity of infection (moi = 10),
      the absence of PKR had no effect on replication of vesicular stomatitis virus
      (VSV) but moderately enhanced encephalomyocarditis virus (EMCV) growth and
      greatly increased replication of herpes simplex virus-1 (HSV-1). Replication of
      EMCV, HSV-1, and VSV was modestly higher in PKR-/- RNAse L-/- fibroblasts when
      compared with control cells. Although the antiviral action of IFN-alpha was
      unaffected by the absence of PKR, IFN action was significantly impaired in the
      double knockout cells but was dependent on the stage of the virus cycle. At early
      stages, it appeared that anti-EMCV and anti-HSV-1 action of IFN-alpha was
      significantly compromised, although weak residual antiviral activity was seen.
      The action of IFN-alpha against VSV was specifically compromised at a late stage
      of virus replication. The results showed that PKR is an important mediator in
      constitutive resistance against HSV-1 and that RNAse L is also necessary for the
      full antiviral activity of IFN against a variety of viruses. These results
      supported the existence of novel pathways aimed toward specific stages of the
      virus life cycle.

PMID- 10926209
TI  - Chromosomal localization of human GRIM-19, a novel IFN-beta and retinoic acid
      activated regulator of cell death.
AB  - Apoptosis is a tightly regulated mechanism that controls the proliferation of
      cells in metazoans. In mammals, multiple genes are required to regulate cell
      death. We have employed a gene expression knockout technique to isolate cell
      death-related genes. One such gene, gene associated with retinoid-interferon
      induced mortality-19 (GRIM-19), is essential for tumor cell death induced by
      interferon-beta (IFN-beta) and retinoic acid (RA). Here, we describe the
      localization of GRIM-19 to human chromosome 19p13.2. This region is essential for
      prostate tumor suppression. Together with its death-inductive role in the IFN
      retinoid-regulated pathways and the tumor-suppressive function of this locus, the
      data suggest that GRIM-19 may be a novel tumor suppressor.

PMID- 10926211
TI  - On the trail of CrO2Cl2 in its reactions with organic compounds
AB  - The simple metal oxo compound chromyl chloride, CrO2Cl2, displays a very complex
      reactivity with respect to alkanes, olefins, alcohols, and epoxides. Synergetic
      investigations applying various techniques and methods have only recently led to
      an understanding of the key steps in the corresponding mechanisms, which are
      representative for more complex systems. Product formation seems to be largely
      determined by radical reactions initiated by this d0-metal compound.

PMID- 10926210
TI  - In vivo neutrophil recruitment by granulocyte chemotactic protein-2 is assisted
      by gelatinase B/MMP-9 in the mouse.
AB  - Granulocyte chemotactic protein-2 (GCP-2) of the mouse is a potent neutrophil
      chemotactic and activating factor in vitro and in vivo. Gelatinase B/matrix
      metalloproteinase-9 is released from neutrophils within 1 h after stimulation
      with GCP-2. In vitro neutrophil chemotaxis by GCP-2 was not impaired by specific
      inhibitory monoclonal antibodies (mAb) against gelatinase B, indicating that
      gelatinase B is not involved in chemotaxis of neutrophils through polycarbonate
      filters. To investigate if gelatinase B degranulation is involved in in vivo cell
      migration toward GCP-2, experiments were performed with gelatinase B knockout
      mice. When mouse GCP-2 was injected intradermally in mice, a dose-dependent
      neutrophil chemotactic response was observed, and this cell migration was
      significantly impaired in young mice by genetic gelatinase B knockout. In adult
      vs. young gelatinase B-deficient mice, such compensatory mechanisms as higher
      basal neutrophil counts and less impairment of chemotaxis toward local GCP-2
      injection were observed. These experiments prove the concept that gelatinase B
      release under pressure of GCP-2 is a relevant, but not exclusive, effector
      mechanism of neutrophil chemotaxis in vivo and that known mechanisms, other than
      the release of gelatinase B, allow for a full-blown chemotactic response and
      compensate for gelatinase B deficiency in adult life in the mouse.

PMID- 10926212
TI  - Catalytic antibodies as magic bullets.
AB  - A reagent capable of detecting and selectively destroying tumor cells while
      leaving healthy cells intact would be a powerful tool for cancer therapy. This
      concept of the magic bullet has been approached by a number of strategies. Here
      we present a recent approach based on catalytic antibodies.

PMID- 10926213
TI  - Programmed chemical systems: multiple subprograms and multiple
      processing/expression of molecular information
AB  - Programmed chemical systems rest on the structural information stored in a
      molecular framework and on its reading and processing through non-covalent
      interactional algorithms to yield specific supramolecular entities. Beyond single
      code self-assembly, which generates exclusively a single, specific
      superstructure, several codes may be implemented in the same overall program,
      thus opening the possibility to perform multiprogramming. Furthermore, the
      reading and processing of the same structural information through different
      interactional algorithms may lead to several different output entities, amounting
      to multiple expression of molecular information. Such features are revealed in
      the formation of double helicates, the assembly of metallosupramolecular
      architectures, and the differential reading of hydrogen bonding patterns in a
      molecular strand. They open novel perspectives within the framework of programmed
      chemical systems, concerning multiple processing capacity, and have intriguing
      implications from the biological point of view.

PMID- 10926214
TI  - Multiple expression of molecular information: enforced generation of different
      supramolecular inorganic architectures by processing of the same ligand
      information through specific coordination algorithms
AB  - The multisubunit ligand 2 combines two complexation substructures known to
      undergo, with specific metal ions, distinct self-assembly processes to form a
      double-helical and a grid-type structure, respectively. The binding information
      contained in this molecular strand may be expected to generate, in a strictly
      predetermined and univocal fashion, two different, well-defined output inorganic
      architectures depending on the set of metal ions, that is, on the coordination
      algorithm used. Indeed, as predicted, the self-assembly of 2 with eight CuII and
      four CuI yields the intertwined structure D1. It results from a crossover of the
      two assembly subprograms and has been fully characterized by crystal structure
      determination. On the other hand, when the instructions of strand 2 are read out
      with a set of eight CuI and four MII (M = Fe, Co, Ni, Cu) ions, the architectures
      C1-C4, resulting from a linear combination of the two subprograms, are obtained,
      as indicated by the available physico-chemical and spectral data. Redox
      interconversion of D1 and C4 has been achieved. These results indicate that the
      same molecular information may yield different output structures depending on how
      it is processed, that is, depending on the interactional (coordination) algorithm
      used to read it. They have wide implications for the design and implementation of
      programmed chemical systems, pointing towards multiprocessing capacity, in a one
      code/ several outputs scheme, of potential significance for molecular computation
      processes and possibly even with respect to information processing in biology.

PMID- 10926215
TI  - Hydrogen-bonding clusters leading to formation of supramolecular dimers of
      metalloporphyrin receptors: modulation of Lewis acidity by pi-pi interactions
AB  - Two remarkable crystal structures are reported of a cyclic receptor 1, containing
      two metalloporphyrin units. The overall crystal structure of 1 provides the first
      direct evidence that pi-stacking between two metalloporphyrins reduces the Lewis
      acidity of the metal ion and thereby dramatically reduces the affinity of zinc
      for external ligands; this effect was previously suggested indirectly by solution
      state binding studies. In addition, crystallising 1 from a different combination
      of solvents and the ability of 1 to distort its structure leads to the remarkable
      observation of a supramolecular dimer of inter-penetrating macrocycles, 4, held
      together by clusters of hydrogen-bonded methanol molecules.

PMID- 10926216
TI  - Evidence for a dinuclear mechanism in alkyne hydrogenations catalyzed by
      pyrazolate-bridged diiridium complexes
AB  - The products obtained from the sequential reaction of [Ir2(mu-H)(mu
      Pz)2H3(NCCH3)(PiPr3)2] (1) with diphenylacetylene and their subsequent reactions
      with hydrogen have been investigated in order to deduce the mechanisms operating
      in the hydrogenation reactions catalyzed by 1. The reaction of 1 with an excess
      of diphenylacetylene gives cis-stilbene and [Ir2(mu-H)(mu-Pz)2-[eta1-C6H4-2-[eta1
      (Z)-C=CHPh]]((Z)-C(Ph) =CHPh](NCCH3)(PiPr3)2] (2), the structure of which has
      been determined by X-ray diffraction. The formation of 2 involves the
      intermediate species [Ir2(mu-H)(mu-Pz)2H2((Z)-C(Ph)=CHPh](NCCH3)
      (PiPr3)2](3),[Ir2(mu-H)(mu-Pz)2H[(Z)-C(Ph)=CHPh]2(NCCH3)(PiPr3)2] (4), and
      [Ir2(mu-H)(mu-Pz)2H[eta1-C6H4-2-[eta1-(Z)-C=CHPh](NCCH3)(PiPr3)2] (5), which have
      been isolated and characterized. These three complexes react with hydrogen to
      give cis-stilbene and 1 and are possible intermediates of the diphenylacetylene
      hydrogenation under catalytic conditions. Nevertheless, the rate of formation of
      5 is very slow compared with the rate of catalytic hydrogenation, which excludes
      its participation during catalysis. Compound 2 also reacts with hydrogen in
      benzene, but in this case the hydrogenation gives 1,2-diphenylethane as the sole
      organic product. The course of this reaction in acetone has been investigated,
      and deuteration experiments were carried out. The formation of [Ir2(mu-H)(mu
      Pz)2H[eta1-C6H4-2-[eta1-(Z)-C=CHPh]](OC(CD3)2)(PiPr3)2] (6) and [Ir2(mu-H)(mu
      Pz)2H[eta1-C6H4-2-[eta1-(Z)-C-CHPh]](NCCH3)(PiPr3)2] (7) was observed under these
      conditions. The experimental evidence obtained supports two alternative
      mechanisms for the alkyne hydrogenation catalyzed by 1, one of them being
      dinuclear and the other mononuclear. The experimental data suggest that the
      former is favored.

PMID- 10926217
TI  - Chiroptical properties of an optically pure dicopper(I) trefoil knot and its
      enantioselectivity in luminescence quenching reactions
AB  - Chiroptical spectroscopy is used to investigate the properties of an optically
      pure dinuclear copper(I) trefoil knot. For the metal-to-ligand charge tranfer
      (MLCT) transition in the visible region (520 nm), the electric and magnetic
      transition dipole moments are determined from absorption and circular dichroism
      spectra: 2.8 Debye and 0.5 Bohr magneton (muB). Circular polarization in the
      luminescence (CPL) of the knot is determined and this allows the electric and
      magnetic transition dipole moments in emission to be calculated: 0.02 Debye and
      0.003 muB. The large difference between the moments in absorption and emission
      shows that the emission observed does not originate directly from the 1MLCT
      state. Given the low probability for radiative decay we assign the long-lived
      emitting excited state to a 3MLCT state. The copper(I) trefoil knot is found to
      quench the emission from TbIII and EuIII(dpa)3(3)-(dpa = pyridine-2,6
      dicarboxylate) with a bimolecular rate constant of 3.2 and 3.3 x 10(7)M(-1)S(-1),
      respectively, at room temperature in water-acetonitrile (1:1 by volume).
      Experimental results indicate that the (lambda)-knot preferentially quenches the
      lambda enantiomer of the lanthanide complex with an enantioselectivity (ratio of
      quenching rate constants for lambda and lambda: kqlambda/kqdelta) of 1.012+/
      0.002 for EuIII and 1.0180+/-0.003 for TbIII.

PMID- 10926219
TI  - Ab initio study of bonding trends among cyanamidophosphates (
AB  - Ab initio calculations on the experimentally known anions [POn(NCN)4-n]3- are
      used to show that intramolecular forces are sufficient to determine their
      existence and structure. Structures are predicted for the analogous
      cyanamidosulphates and perchlorates. If one of the oxygens of the XO4q group is
      replaced by nitrogen or fluorine, further new anions are obtained. An example is
      NSO3(3)-. Remarkably, the NArO3- anion is predicted to have strong inner bonding
      and is, together with ArO4, a candidate for an argon species.

PMID- 10926218
TI  - Rigidified calixarenes bearing four carbamoylmethylphosphineoxide or
      carbamoylmethylphosphoryl functions at the wide rim
AB  - Conformationally rigidified tetraCMPO derivatives have been prepared from
      calix[4]arene bis(crown ether) 4a in which adjacent oxygens are bridged at the
      narrow rim by two diethylene glycol links. Acylation of the tetraamine 4c with
      the CMPO-active ester 5b gave the tetraphosphine oxide 6a, while the
      tetraphosphinate 6b and the tetraphosphonate 6c were obtained by Arbuzov reaction
      of tetrabromoacetamido derivative 7 with PhP(OEt)2 or P(OEt)3. The extraction
      ability of these CMPO derivatives was checked for selected lanthanides and
      actinides and compared with the analogous compounds 1b, 10b and 10d derived from
      calix[4]arene tetrapentyl ether. All rigidified bis(crown ether) ligands are more
      effective extractants than their pentyl ether counterparts and require only 1/10
      of the concentration (cL= 10 4M) to obtain the same distribution coefficients,
      while with CMPO itself a 2,000-fold concentration is necessary. This could be a
      consequence of a better preorganisation of the ligating functions owing to the
      rigidity which on the other hand did not change the observed selectivity for
      americium (DAm/DEu=9-19) and for light lanthanides over heavy ones. NMR
      relaxivity titration curves show that the complex of Gd3+ with ligand 6a is
      highly oligomerised in anhydrous acetonitrile over a large range of ligand:metal
      concentration ratios. Nuclear magnetic relaxation dispersion (NMRD) profiles also
      showed that large oligomers were formed, and their mean tumbling times were
      deduced from the Solomon-Bloembergen-Morgan equations. The NMR spectra of dia-
      and paramagnetic lanthanide complexes with 6a agreed with the presence of two
      conformers with an elongated calix[4]arene skeleton in which the distances
      between opposite methylene groups are different. Contrary to what was observed
      with ligand 2a, the addition of nitrate ions does not labilize the metal
      complexes, presumably because of the rigidification effect of the ether bridges.
      Single-crystal X-ray structures were obtained for the active ester 5b and for
      diphenylphosphorylacetic acid 5a.

PMID- 10926220
TI  - Catalytic oxidation with a non-heme iron complex that generates a low-spin
      Fe(III)OOH intermediate
AB  - The antitumor drug bleomycin (BLM) is proposed to act via a low-spin iron(III)
      hydroperoxide intermediate called "activated bleomycin". To gain more insight
      into the mechanistic aspects of catalytic oxidation by these intermediates we
      have studied the reactivity of [(N4Py)Fe(CH3CN)](ClO4)2 (1) (N4Py = N,N-bis(2
      pyridylmethyl)-N-bis(2-pyridyl)methylamine) with excess H2O2. Under these
      conditions a transient purple species is generated, [(N4Py)FeOOH]2- (2), which
      has spectroscopic features and reactivity strongly reminiscent of activated
      bleomycin. The catalytic oxidation of alkanes such as cyclohexane, cyclooctane,
      and adamantane by 1 with H2O2 gave the corresponding alcohols and ketones in up
      to 31% yield. It was concluded, from the O2 sensitivity of the oxidation
      reactions, the formation of brominated products in the presence of methylene
      bromide, and the nonstereospecificity of the oxidation of cis- or trans
      dimethylcyclohexane, that long-lived alkyl radicals were formed during the
      oxidations. Oxidation of alkenes did not afford the corresponding epoxides in
      good yields but resulted instead in allylic oxidation products in the case of
      cyclohexene, and cleavage of the double bond in the case of styrene. Addition of
      hydroxyl radical traps, such as benzene and acetone, led to only partial
      quenching of the reactivity. The kinetic isotope effects for cyclohexanol
      formation, ranging from 1.5 in acetonitrile to 2.7 in acetone with slow addition
      of H2O2, suggested the involvement of a more selective oxidizing species in
      addition to hydroxyl radicals. Monitoring the UV/Vis absorption of 2 during the
      catalytic reaction showed that 2 was the precursor for the active species. On the
      basis of these results it is proposed that 2 reacts through homolysis of the O-O
      bond to afford two reactive radical species: [(N4Py)Fe(IV)O]2+ and *OH. The
      comparable reactivity of 1 and Fe-BLM raises the possibility that they react
      through similar mechanistic pathways.

PMID- 10926221
TI  - The carbenoid approach to peptide synthesis.
AB  - A different approach to the synthesis of dipeptides is described based on the
      formation of the NHCHR1CONH-CHR2CO bond by carbenoid N-H insertion, rather than
      the formation of the peptide bond itself. Thus decomposition of triethyl
      diazophosphonoacetate catalysed by rhodium(II) acetate in the presence of N
      protected amino acid amides 8 gives the phosphonates 9. Subsequent Wadsworth
      Emmons reaction of 9 with aldehydes in the presence of DBU gives dehydro
      dipeptides 10. The reaction has been extended to a simple two-step procedure,
      without the isolation of the intermediate phosphonate, for conversion of a range
      of amino acid amides 11 into dehydro dipeptides 12 and to an N-methylamide 11 h,
      and for conversion of a dipeptide to tripeptide (13-->14). Direct conversion, by
      using methyl diazophenylacetate, of amino acid amides to phenylglycine-containing
      dipeptides 19 proceeds in good chemical yield, but with poor
      diastereoselectivity.

PMID- 10926222
TI  - Synthesis of unsymmetrically substituted subphthalocyanines
AB  - A series of new unsymmetrically substituted subphthalocyanines containing iodo or
      octylthioether substituents on the outer aromatic rings have been synthesized.
      The statistical reaction of one equivalent of 1,2-dicyano-3-iodobenzene whether
      with two equivalents of 1,2-dicyano-4-octylthiobenzene or with two equivalents of
      1,2dicyano-4,5-dioctylthiobenzene in the presence of boron trichloride in 1
      chloronaphthalene yielded in both cases all the possible expected unsymmetrically
      substituted subphthalocyanines, which were separated by column chromatography on
      silica gel. All compounds were identified by FAB mass spectrometry and then
      characterized by HR-LSIMS spectrometry. The unambiguous characterization of each
      constitutional isomer was made possible by careful examination of the symmetry
      environment experienced by each proton on their 1H-NMR spectra.

PMID- 10926223
TI  - Crystalline self-assembly into monolayers of folded oligomers at the air-water
      interface
AB  - Insertion of the 1,3-bis(ethynylene)benzene unit as a rigid spacer into a linear
      alkyl chain, thus separating the two resulting stems by 9 A. induces chain
      folding at the air-water interface. These folded molecules self-assemble into
      crystalline monolayers at this interface, with the plane of the folding unit
      almost perpendicular to the water surface, as determined by synchrotron grazing
      incidence X-ray diffraction. Three distinct molecular shapes, of the types U,
      inverted U, and M, were obtained in the two-dimensional crystalline state,
      depending upon the number of spacer units, and the number and position of the
      hydrophilic groups in the molecule. The molecules form ribbons with a higher
      crystal coherence in the direction of stacking between the molecular ribbons, and
      a lower coherence along the ribbon direction. A similar molecule, but with a
      spacer unit that imposes a 5 A separation between alkyl chains, yields the
      conventional herringbone arrangement.

PMID- 10926224
TI  - Selective electrolytic removal of bis(alkoxycarbonyl)methano addends from C60 bis
      adducts and electrochemical stability of C70 derivatives
AB  - The novel mixed bis-adducts of C60, (+/-)-4-(+/-)-8 and 9, with a
      bis(ethoxycarbonyl)methano addend (Bingel addend) and a second addend
      ([1,2]benzeno, but[2]eno, methaniminomethano, or diarylmethano) bridging 6,6
      closed bonds of the carbon sphere were synthesized in two-step reactions. Each
      bis-adduct was exhaustively electrolyzed at the potential of the second fullerene
      centered reduction step, resulting in the selective removal of the Bingel addend
      (retro-Bingel reaction) to produce the corresponding mono-adducts, which were
      isolated in yields of over 60%. These results open up the possibility of using
      the Bingel addend as a temporary protecting and directing group in the
      construction of multiple adducts of C60 with unusual addition patterns. The
      Bingel-type mono-adduct of C70 10 and the constitutionally isomeric bis-adducts
      11, (+/-)-12, and (+/-)-13 were also included in this investigation. A large
      difference in the electrochemical behavior between C70 bis-adducts and the
      corresponding C60 derivatives was observed. Thus, the intramolecular "walk-on-the
      sphere" isomerization which occurs readily with Bingel-type bis-adducts of C60
      under the conditions of two-electron controlled potential electrolysis (CPE) is
      only a minor reaction pathway in the series of C70 derivatives. The latter
      preferentially undergo retro-Bingel reaction.

PMID- 10926225
TI  - An unsymmetrical tripodal ligand with an N2OS donor set: coordination chemistry
      with nickel(II)ions and aerial oxidation to the sulfinate complex
AB  - The synthesis of the previously unknown tripodal ligand H4-1 is reported. The
      tetradentate ligand is equipped with a completely unsymmetrical N2OS donor set.
      It reacts with Ni(OAc)2. 4H2O or Ni(ClO4)2.6H2O to give the multinuclear
      nickel(II) complexes [Ni(H-1-Imin)(OAc)]2 (2) (which contains a coordinated
      Schiff base obtained by reation of the primary amine with the acetone solvent)
      and [Ni3(H3-1)(H2-1)2]-ClO4.H2O.3 MeCN (3), respectively. A solution of 3 in DMF
      is readily oxidized upon exposure to air or by aqueous H2O2 to yield [Ni(H2-1
      sulfinate)]2. 2MeOH (4). The molecular structures of 2-4 have been determined by
      X-ray diffraction. Complex 2 exhibits a strongly distorted, octahedral
      coordination geometry around each nickel(II)ion. The primary amino group of the
      ligand in this case reacted with the solvent acetone to yield a Schiff base which
      is coordinated to the metal center. The molecular structure of the trinuclear
      complex cation in 3 consists of two subunits: a nickel atom with a square-planar
      N2S2 coordination geometry and two other nickel atoms with a trigonal-bipyramidal
      N2O2S coordination environment. The dinuclear complex 4 shows distorted
      octahedral geometry around each nickel(II) ion. The thiolato groups of the
      ligands are oxidized to sulfinato groups which are O,O-bound to the nickel
      center. This coordination mode is unusual for nickel sulfinate complexes.

PMID- 10926226
TI  - Highly chemoselective hydrogenation with retention of the epoxide function using
      a heterogeneous Pd/C-ethylenediamine catalyst and THF
AB  - In general, palladium-carbon (Pd/C) catalyzed hydrogenation of epoxides affords
      the corresponding primary and secondary alcohols as a mixture. It has been found
      that the catalytic activity of a Pd/C -ethylenediamine complex catalyst
      [Pd/C(en)] in the hydrogenolysis of epoxide functions is drastically reduced.
      Herein we describe a mild and chemoselective method for the hydrogenation of
      olefin, nitro, and azide functions with retention of the epoxide function. The
      chemoselectivity was accomplished by using a combination of 5% Pd/C(en) and THF
      as solvent. A significant drop in the chemoselectivity of the hydrogenation is
      observed with 5% Pd/C(en) in MeOH. These results reinforce the utility of
      epoxides as important precursors of alcohols in synthetic chemistry.

PMID- 10926227
TI  - Detection of nitrobenzene, DNT, and TNT vapors by quenching of porous silicon
      photoluminescence
AB  - The detection of nitroaromatic molecules in air by the quenching of the
      photoluminescence of porous silicon (porous Si) films has been explored.
      Detection is achieved by monitoring the photoluminescence (PL) of a
      nanocrystalline porous Si film on exposure to the analyte of interest in a
      flowing air stream. The photoluminescence is quenched on exposure to the
      nitroaromatic, presumably by an electron-transfer mechanism. Detection limits of
      500 parts-per-billion (ppb), 2 ppb, and 1 ppb were observed for nitrobenzene, 2.4
      dinitrotoluene (DNT), and 2,4,6-trinitrotoluene (TNT), respectively (exposure
      times of 5 min for each, in air). Specificity for detection is achieved by
      catalytic oxidation of the nitroaromatic compound. A platinum oxide (PtO2) or
      palladium oxide (PdO) catalyst at 250 degrees C. placed in the carrier gas line
      upstream of the porous Si detector, causes oxidation of all the nitroaromatic
      compounds studied. The catalyst does not oxidize benzene vapor, and control
      experiments show no difference in the extent of PL quenching by benzene with or
      without an upstream catalyst. The PL quenching by NO2, released in the catalytic
      oxidation of nitroaromatic compounds, is less efficient than the quenching of the
      intact nitroaromatic compound. This provides a means to discriminate nitro
      containing molecules from other organic species.

PMID- 10926228
TI  - Reactive-site design in folded-polypeptide catalysts--the leaving group pKa of
      reactive esters sets the stage for cooperativity in nucleophilic and general-acid
      catalysis.
AB  - The second-order rate constants for the hydrolysis of nitrophenyl esters
      catalysed by a number of folded designed polypeptides have been determined, and
      1900-fold rate enhancements over those of the 4-methylimidazole-catalysed
      reactions have been observed. The rate enhancements are much larger than those
      expected from the pKa depression of the nucleophilic His residues alone. Kinetic
      solvent isotope effects were observed at pH values lower than the pKa values of
      the leaving groups and suggests that general-acid catalysis contributes in the pH
      range where the leaving group is predominantly protonated. In contrast, no
      isotope effects were observed at pH values above the pKa of the leaving group. A
      Hammett rho value of 1.4 has been determined for the peptide-catalysed hydrolysis
      reaction by variation of the substituents of the leaving phenol. The
      corresponding values for the imidazole-catalysed reaction is 0.8 and for phenol
      dissociation is 2.2. There is therefore, very approximately, half a negative
      charge localised on the phenolate oxygen in the transition state in agreement
      with the conclusion that transition-state hydrogen-bond formation may contribute
      to the observed catalysis. The elucidation at a molecular level of the principles
      that control cooperativity in the biocatalysed ester-hydrolysis reaction
      represents the first step towards a level of understanding of the concept of
      cooperativity that may eventually allow us to design tailor-made enzymes for
      chemical reactions not catalysed by nature.

PMID- 10926229
TI  - Oligomerisation of ethylene by bis(imino)pyridyliron and -cobalt complexes
AB  - A series of bis(imino)pyridyliron and -cobalt complexes [[2,6-(CR=NAr)2C5H3N]MX2]
      (R=H, Me; M=Fe, Co; X=Cl, Br) 8-16 containing imino-aryl rings (Ar) with at least
      one small ortho substituent, as well as Ar=biphenyl and Ar=naphthyl, has been
      synthesised. Crystallographic analyses of complexes 9 (Ar = 2,3-dimethylphenyl),
      13 and 14 (Ar= biphenyl; X= Cl or Br, respectively) reveal a distorted trigonal
      bipyramidal geometry in the solid state. These complexes, in combination with
      methyl aluminoxane (MAO), are active catalysts for the oligomerisation of
      ethylene, yielding >99% linear alpha-olefin mixtures that follow a Schulz-Flory
      distribution. Iron ketimine (R = Me) precatalysts give the highest activities and
      a greater alpha-value than their aldimine (R = H) analogues. Cobalt precatalysts
      follow a similar trend, though their activities are almost two orders of
      magnitude lower than those of the corresponding iron catalysts. Ethylene pressure
      studies on cobalt precatalyst 15 reveal a first-order dependence on ethylene for
      both the rate of propagation and the rate of chain transfer, and a pressure
      independence of the alpha value.

PMID- 10926230
TI  - Crossed-beam study of Co+(3F4)+propane: experiment and density functional theory
AB  - A pulsed beam of Co+(3F4) crosses a pulsed beam of C3H8 or C3D8 gas under single
      collision conditions at collision energies of 0.01 eV and 0.21 eV. After a
      variable time delay t(ext) = 1-8 micros a fast high voltage pulse extracts
      product ions into a field-free flight tube for mass analysis. Consistent with
      earlier work, we observe prompt CoC3H6+ +H2 elimination products in 3:1 excess
      over CoC2H4+ +CH4 products at 0.21 eV on a 2-10 micros time scale. Long-lived
      CoC3H8+ complexes fragment predominantly back to Co+ +C3H8 reactants and to H2
      elimination products on a 6-24 micros time scale. Density functional theory
      (B3LYP) calculations provide energies, geometries, and harmonic vibrational
      frequencies at key stationary points for use in a statistical rate model of the
      reaction. By adjusting two key multicenter transition state (MCTS) energies
      downward by 4-7 kcal mol(-1), we obtain good agreement with our decay time
      results and with the cross section versus collision energy of Armentrout and co
      workers from 0.1-1.0 eV. B3LYP theory succeeds in finding relative energies of
      the MCTSs leading to CH4 and H2 in the proper order to explain the different
      product branching ratio for Co+ (which favors H2 over CH4) compared with its
      nearest neighbors Fe+ and Ni+ (which favor CH4 over H2).

PMID- 10926231
TI  - Photomagnetic properties in a series of spin crossover compounds
AB  - The spin crossover (SC) compounds [Fe(PM-AzA)2(NCX)2] and [Fe(PM-FIA)2(NCX)2]
      (with PM-AzA = N-2'-pyridylmethylene-4-(phe-nylazo)aniline, PM-FIA = N-2'
      pyridylmethylene-4-(2-amino)fluorene, and X = S, Se) have been prepared. The SC
      regimes have been deduced from variable-temperature magnetic susceptibility data.
      The enthalpy and entropy changes associated with the SC have been evaluated from
      DSC measurements. A cooperativity factor, C, has been defined, and its values for
      the different compounds have been deduced from the spin crossover curves. At 10
      K, the light-induced excited spin state trapping (LIESST) effect has been
      observed within the cavity of the SQUID magnetometer. The critical temperatures
      Tc(LIESST) have been determined for [Fe(PM-AzA)2(NCS)2] and [Fe(PM-F1A)2(NCX)2],
      and the role of cooperativity has been analyzed. A linear correlation has been
      found between the Tc(LIESST) and C values. The kinetics of HS-->LS relaxation
      have been investigated; a thermally activated mechanism at elevated temperatures
      and a nearly temperature independent relaxation behavior at low temperatures have
      been found. Finally, the magnetic behavior recorded under light irradiation in
      the warming and cooling modes has revealed the occurrence of the light-induced
      thermal hysteresis (LITH) effect.

PMID- 10926232
TI  - A new route into single-crystalline partially oxidized cobalt compounds:
      reactions with zintl-type hexaselenodistannate(III) K6Sn2Se6 as mild oxidant
AB  - Reactions of K6Sn2Se6 (1) with [Cp*CoCl]2 were investigated in order to probe the
      stability of the formal +3 oxidation state at Sn and possible ligand properties
      of heteroatomic zintl-type anion "Sn2Se6(6)- ". From these experiments, we
      obtained the following compounds that are oxidized to different extent as a
      result of the reaction with SnIII: [Cp2*Co][Cl2Co(mu2-Cl)2Li(thf)2] (2),
      [(Cp*Co)3(mu-Se)2] (3), [(Cp*Co)3(mu3-Se)2][Cl2Co(mu2-Cl)2Li(thf)2] (4), and
      [(Cp*Co)4(mu3-Se)4] (5). These compounds were structurally characterized by
      single-crystal X-ray diffractometry. It shows that the reaction conditions
      strongly affect the type and oxidation state of the isolated product. Two of the
      observed compounds, 3 and 4, are closely related both structurally and
      electronically; this is discussed and further illustrated by cyclovoltammetric
      measurements. The choice of the terminal Cp* ligand attached to the transition
      metal in the reactand complex is assumed to be basically dependent for the
      alignment of unexpected structural details when compared with known compounds of
      similar compositions. In conclusion, 1 is observed to act as mild oxidant as well
      as selenide donor, but is not in the position to keep its Sn-Se framework under
      the given reaction conditions.

PMID- 10926233
TI  - Self-complementary
AB  - Three [3]catenanes with cavities large enough to accommodate aromatic guests have
      been designed and synthesized (yields = 5-20 %) by means of kinetically
      controlled self-assembly processes. The X-ray structural analysis of one of three
      [3]catenanes confirmed the presence of a rectangular cavity (dimensions = 7 x 11
      A) lined by pi-electron-rich recognition sites and hydrogen-bond acceptor groups.
      In spite of their apparently ideal recognition features, none of these
      [3]catenanes bind guests incorporating a pi-electron-deficient bipyridinium unit.
      However, the template-directed syntheses of the [3]catenanes also produce, in
      yields of 2-23%, [2]catenanes incorporating a 1,5-dioxynaphtho[38]crown-10
      interlocked with a bipyridinium-based tetracationic cyclophane. The X-ray
      structural analyses of two of these [2]catenanes revealed that a combination of
      [pi...pi] and [C-H...pi] interactions is responsible for the formation of
      supramolecular homodimers in the solid state. 1H NMR spectroscopic investigations
      of the four [2]catenanes demonstrated that supramolecular homodimers are also
      formed (Ka= 17-31M(-1), T= 185 K) in (CD3)2CO solutions. Dynamic 1H NMR
      spectroscopy revealed that the 1,5-dioxynaphtho[38]crown-10 and tetracationic
      cyclophane components in the four [2]catenanes and in the three [3]catenanes
      circumrotate (deltaGc(not equal to) = 9-14 kcal mol(-1)) through each other's
      cavity in (CD3)2CO. Similarly, the 1,5-dioxynaphthalene and the bipyridinium ring
      systems rotate (deltaGc(not equal to) =10-14 kcal mol(-1)) about their [O...O]
      and [N...N] axes, respectively, in solution.

PMID- 10926234
TI  - The influence of macrocyclic polyether constitution upon ammonium ion/crown ether
      recognition processes
AB  - Secondary dialkylammonium (R2NH2+) ions are bound readily by dibenzo[24]crown-8
      (DB24C8) to form threaded complexes, namely [2]pseudo-rotaxanes. The effect of
      replacing one or both of the catechol rings in DB24C8 with resorcinol rings upon
      the crown ether's ability to bind R2NH2+ ions has now been investigated. When
      only one aromatic ring is changed from catechol to resorcinol, a crown ether with
      a [25]crown-8 constitution is created-namely benzometaphenylene[25]crown-8
      (BMP25C8). A [2]pseudorotaxane is formed in the solid state when BMP25C8 is co
      crystallized with dibenzylammonium hexafluorophosphate, as evidenced by its X-ray
      crystal structure. Furthermore, this crown ether has been shown to bind R2NH2+
      ions in solution, an observation which has been exploited in the synthesis of the
      first BMP25C8-containing [2]rotaxane. The methodology employed to generate this
      [2]rotaxane--the reaction of an amine with an isocyanate to form a urea--was
      tested initially on a system incorporating DB24C8 and was shown to work
      efficiently. Both [2]rotaxanes have been fully characterized by 1H and 13C NMR
      spectroscopies, FAB mass spectrometry and X-ray crystallography. Interestingly,
      the unsymmetrical nature of the dumbbell-shaped component in each of the two
      [2]rotaxanes renders each face of the encircling macrocyclic polyether
      diastereotopic, a feature that is apparent upon inspection of their 1H NMR
      spectra. The resonances associated with the diastereotopic protons on each face
      of the macrorings are well enough resolved to enable the faces of the crown
      ethers to be readily identified with respect to their protons by 1H NMR
      spectroscopy. Unambiguous assignments can be made as a result of the fact that
      the protons on each face of the macrocyclic polyether experience a unique set of
      through-space interactions, as evidenced by T-ROESY experiments. Additionally,
      the two-dimensional NMR analyses are in agreement with the X-ray crystallographic
      studies performed on these [2]rotaxanes, indicating that the crown ethers are
      located intimately around the NH2+ centers as expected. Replacement of both
      catechol rings in the DB24C8 constitution with resorcinol rings results in a
      crown ether with a [26]crown-8 constitution--namely bismetaphenylene[26]crown-8
      (BMP26CS). All the evidence to date points to the fact that this further change
      in constitution results in a crown ether that does not bind R2NH2+ ions in either
      the solution or solid states.

PMID- 10926235
TI  - A molecular dynamics study of the structure and evolution of the 4,4'
      bis(diphenylhydroxymethyl)biphenyl/acetone host-guest system
AB  - The 4,4'-bis(diphenylhydroxymethyl)biphenyl/acetone (DHMB-Ac) system was studied
      by NPT molecular dynamics (MD) calculations; the study was prompted by the
      availability of X-ray single-crystal diffraction and calorimetric data (L.
      Johnson, L. Nassimbeni, E. Weber and K. Skobridis, J. Chem. Soc. Perkin Trans. 2,
      1992, 2131). Potential energies were calculated by using the UNI-FF or the OPLS
      all-atom force fields. The kinetics of formation of hydrogen-bonded aggregates
      between the DHMB molecule and acetone was sampled, and the persistence and
      fluxionality of the O-H...O=C hydrogen bond are clearly revealed. Extensive MD
      runs at variable temperature on the inclusion compound in its crystalline state
      allow a description of the thermal motion and eventual reorientation within its
      cavity of the acetone molecule; the host crystalline matrix does not survive when
      guests are removed. The dynamic evolution of a slab of 60 DHMB and 120 acetone
      molecules. which has the experimental crystal structure, was also simulated at
      the temperature experimentally observed for guest desorption, and the loss of
      solvent molecules was monitored. Crystalline order is very quickly lost; then,
      guest molecules can easily diffuse away from the surface without a noticeable
      swelling of the material. The molecular reorganization of the remaining host
      liquid back to the crystal structure of one of the two polymorphs of pure DHMB
      could not be observed, owing to the short simulation times and to the smallness
      of the computational sample.

PMID- 10926236
TI  - Open reduction and augmentation of internal fixation with an injectable skeletal
      cement for the treatment of complex calcaneal fractures.
AB  - OBJECTIVES: To describe the surgical handling, potential complications, and
      remodeling of an injectable, osteoconductive calcium phosphate cement (Norian
      SRS) for joint depression-type calcaneal fractures in humans, and to illustrate
      the clinical efficacy of this cement with special reference to early
      postoperative full weight bearing. DESIGN: Prospective cohort study. SETTING:
      Level I trauma centers in Bochum and Leipzig, Germany. INTERVENTION: Thirty-six
      joint depression type calcaneal fractures in thirty-two patients were augmented
      with the calcium phosphate cement after standard open reduction with internal
      fixation. Postoperative full weight bearing was allowed progressively earlier,
      and as the study progressed, the last patients were bearing full weight as early
      as three weeks postoperatively. Biopsies for histologic analysis were performed
      at time of hardware removal after one year (seven biopsies) or in case of
      infection at time of debridement (five biopsies). MAIN OUTCOME MEASURES: Clinical
      outcome was evaluated according to a calcaneal scoring system. Data were compared
      and statistically analyzed between patients with postoperative full weight
      bearing after eight to twelve weeks and three to six weeks, respectively.
      Histologic findings are described. RESULTS: Cement injection averaged ten cubic
      centimeters and could easily be performed under fluoroscopic control.
      Progressively earlier full weight-bearing was achieved without loss of reduction.
      There was no statistical difference in clinical outcome scores in patients with
      full weight bearing before or after six weeks postoperatively. The infection rate
      was 11 percent, possibly related to the skin incisions. The biopsies from
      clinically satisfactory cases showed nearly complete bone apposition, areas of
      vascular penetration, and reversal lines illustrating progressive cycles of
      resorption and new bone formation. Biopsy specimens from infected cases showed
      bone and cement surrounded by either fibrous tissue or acute inflammation without
      extensive bone apposition. CONCLUSIONS: Calcium phosphate cement augmentation of
      standard open reduction with internal fixation in joint-depression type calcaneal
      fractures allows postoperative full weight bearing as early as three weeks
      postoperatively. The injectable bone cement can easily be handled surgically
      under fluoroscopic control and has proved to be remodelable.

PMID- 10926237
TI  - Biomechanical evaluation of the dynamic hip screw with two- and four-hole side
      plates.
AB  - OBJECTIVES: To determine the biomechanical strength and stiffness of a dynamic
      hip screw (DHS; Synthes USA, Paoli, PA, U.S.A.) with a two-hole side-plate as
      compared with a four-hole side-plate design for the reconstruction of unstable
      three-part intertrochanteric fractures. DESIGN: Eight matched pairs of embalmed
      human femurs were tested in two modes: (a) 2,000 cycles of simulated physiologic
      loading; (b) test to failure. SETTING: Laboratory. Simulated single leg stance
      using a simulated pelvic loading mechanism with abductor loading. Strain and
      displacement sensors were used to measure fragment shear and distraction and
      surface strain in the proximal side plate. SPECIMENS: Eight pairs of skeletonized
      embalmed cadaveric specimens were selected on the basis of femoral neck angle and
      absence of old fracture, anatomic anomaly, or pathology. INTERVENTION: The
      specimens were divided into two groups: (a) left femurs received the two-hole
      side-plate design; (b) right femurs received the four-hole side-plate design. All
      fractures were reconstructed by the same surgeon using the manufacturer's
      instructions. MAIN OUTCOME MEASUREMENTS: Implant placement was verified by
      radiographic measurement of tip-to-apex distance. In cyclic testing, the amount
      of femoral neck fragment migration in both distraction and shear was quantified.
      Strain magnitude in the side plate was measured in both cyclic and failure
      testing. The peak load withstood by the reconstruction was quantified in the
      failure test. RESULTS AND CONCLUSIONS: Peak load in the failure test was not
      found to be statistically different between the two-hole and four-hole designs.
      In cyclic testing, the two-hole configuration exhibited statistically smaller
      fragment migration in both shear and distraction than the four-hole design (p <
      0.05). The strain magnitude in the side plate was not statistically different in
      the cyclic or failure tests. The femurs with a greater neck angle failed by
      crushing of the bone in the neck. The femurs with a lesser neck angle failed due
      to bending of the hardware. The results of this investigation revealed that the
      two-hole DHS is biomechanically as stable as the four-hole DHS in cyclic and
      failure loads under the conditions tested. These results, in concert with
      clinical experience, can be used to support the use of the two-hole DHS for the
      reconstruction of intertrochanteric fractures without a diaphyseal extension.

PMID- 10926238
TI  - Intertrochanteric-subtrochanteric fractures: treatment with the long Gamma nail.
AB  - OBJECTIVE: To evaluate the outcome of the treatment of intertrochanteric
      subtrochanteric fractures (subtrochanteric fractures with extension into the
      greater trochanter and the piriformis fossa) using the long Gamma nail. DESIGN:
      Prospective, consecutive. SETTING: Multicenter (private clinics). PATIENTS: Fifty
      two closed intertrochanteric-subtrochanteric fractures in nonpathologic bone in
      fifty-two consecutive patients with a mean age of forty-five years (range, 18 to
      91 years). INTERVENTION: Closed reduction and internal fixation with the long
      Gamma nail. MAIN OUTCOME MEASUREMENTS: Analysis of clinical and radiologic
      results with emphasis on the incidence of complications. Outcome assessment
      comparing the preinjury status of every patient with the status at a minimum
      follow-up of twelve months. RESULTS: At one year, seven patients had died and two
      other patients were lost to follow-up. Thus, forty-three of the fifty-two
      patients completed a prospective follow-up averaging sixteen months (range, 12 to
      31 months). All fractures united within an average of 4.3 months (range, 3 to 6.5
      months). Mechanical complications (breakage of the distal locking bolts) occurred
      in one fracture. Two patients had more than 5 degrees but less than 10 degrees of
      deformity in varus and more than one but less than 2.5 centimeters of shortening;
      two had more than 5 degrees of deformity in varus; and two had up to one
      centimeter of shortening. Two patients had other severe injuries that influenced
      the end result. Thirty-four of the remaining forty-one patients (82.9 percent)
      were restored to their preinjury status. There was no direct relationship between
      the radiologic and the functional results: an excellent radiologic result was not
      uniformly associated with an excellent functional outcome. CONCLUSIONS: Closed
      reduction and long Gamma nailing of intertrochanteric-subtrochanteric fractures
      enables the orthopaedic surgeon to treat these fractures with a minimally
      invasive procedure and a negligible rate of mechanical complications. The rate of
      union was 100 percent in this series. The rate of restitution to the preinjury
      status was high.

PMID- 10926239
TI  - Effect of previous cerebrovascular accident on outcome after hip fracture.
AB  - OBJECTIVE: To evaluate the effect of previous cerebrovascular accident on outcome
      after hip fracture. STUDY DESIGN: Prospective, consecutive. PATIENTS: From July
      1987 to March 1997, 862 community-dwelling patients sixty-five years of age or
      older who had sustained an operatively treated femoral neck or intertrochanteric
      fracture were prospectively followed. INTERVENTION: All patients had operative
      fracture treatment. MAIN OUTCOME MEASUREMENTS: Postoperative complications, in
      hospital mortality, hospital length of stay, hospital discharge status, one-year
      mortality and place of residence, and return to preinjury ambulatory level, basic
      and instrumental activities of daily living status. RESULTS: Sixty-three patients
      (7.3 percent) had a history of cerebrovascular accident; the fracture was on the
      hemiplegic side in forty-six (86.8 percent) of the fifty-three patients with
      hemiplegia. Patients who had a history of cerebrovascular accident were more
      likely to be male and have an American Society of Anesthesiologists (ASA) rating
      of III or IV. They were also more likely to have three or more comorbidities, be
      a home ambulator, and be dependent on basic and instrumental activities of daily
      living before hip fracture. Hospital length of stay was significantly higher for
      patients who had a history of cerebrovascular accident. There were no differences
      in the incidence of hospital mortality or one-year mortality between patients who
      did and did not have a history of cerebrovascular accident before hip fracture.
      In addition, at one-year follow-up, when controlling for prefracture level of
      function, there were no differences in the rate of functional recovery between
      the two groups of patients. CONCLUSIONS: The functional recovery of elderly hip
      fracture patients who had a prior cerebrovascular accident was similar to that of
      patients who had no history of a prior cerebrovascular accident.

PMID- 10926240
TI  - Failure of exchange reamed intramedullary nails for ununited femoral shaft
      fractures.
AB  - OBJECTIVE: To determine the effectiveness of exchange reamed nails for treatment
      of aseptic femoral delayed unions and nonunions. DESIGN: Retrospective chart
      review. PATIENTS: Nineteen patients admitted to the Carolinas Medical Center
      Level I trauma center from 1990 to 1996 for repair of femoral shaft fracture
      nonunion following contemporary locked nailing performed at least six months
      previously. These patients showed no radiographic evidence of progression of
      fracture healing for three months and had clinical symptoms of nonunion.
      INTERVENTION: Exchange reamed nails to treat ununited femoral shaft fracture.
      MAIN OUTCOME MEASUREMENTS: Radiographic and clinical evidence of union of the
      fracture or of the necessity for additional procedures. RESULTS: In 53 percent of
      the patients the secondary procedure resulted in fracture union, whereas in 47
      percent, one or more additional procedures were required. Eight of the nine
      fractures that did not unite with exchange nailing united after a subsequent
      procedure (bone grafting, compression plating, or nail dynamization). Neither the
      type of nonunion, the location of the shaft fracture, the use of static versus
      dynamic cross-locking, nor the use of tobacco products was statistically
      predictive of the need for additional procedures. CONCLUSIONS: Reevaluation of
      routine exchange nailing as the recommended treatment for aseptic femoral delayed
      union or nonunion may be required. A significant number of patients who undergo
      reamed exchange nailing will require additional procedures to achieve fracture
      healing.

PMID- 10926241
TI  - Treatment of complex (Schatzker Type VI) fractures of the tibial plateau with
      circular wire external fixation: retrospective case review.
AB  - OBJECTIVE: To determine the effectiveness of circular wire external fixation in
      the treatment of complex (Schatzker Type VI) fractures of the tibial plateau.
      DESIGN: Retrospective case series. SETTING: Fifty-seven complex (Schatzker Type
      VI) fractures of the tibial plateau were treated with circular wire external
      fixation at a Level 1 trauma center. PATIENTS: Thirty-five fractures were closed,
      and twenty-two were open. INTERVENTION: Closed indirect reduction by
      ligamentotaxis was attempted in all fractures; limited open reduction was
      performed in seven. Conventional Ilizarov frames using wire fixation were used in
      thirty-two fractures. The remaining twenty-five fractures were treated with
      hybrid Ilizarov fixators, which differed from conventional Ilizarov frames only
      in the use of cortical bone pins rather than wires through the distal rings for
      fixation of the diaphysis. MAIN OUTCOME MEASUREMENT: The results were graded
      according to the Knee Society rating system. Follow-up ranged from 16 to 90
      months and averaged 42 months. RESULTS: All fractures united at an average of 173
      days (range, 50 to 415 days). Forty-five fractures with anatomic reduction had an
      average knee score of eighty-three and an average functional score of sixty-nine.
      In nine fractures with nonanatomic reduction, the average knee score was fifty
      two, and the functional score was nineteen. CONCLUSIONS: Results perhaps would
      have been improved by more frequent open reduction, bone grafting, and internal
      fixation of fractures with severely depressed articular fragments. However, the
      use of circular external fixation obtained results comparable with other series,
      and we believe it is appropriate for treatment of these complex tibial fractures,
      especially those with a poor soft-tissue envelope.

PMID- 10926242
TI  - Tibial tubercle-medial malleolar distance in determining tibial nail length.
AB  - OBJECTIVE: To assess the accuracy of a previously undescribed method of
      determining tibial nail length based on anatomic landmarks. DESIGN: Cadaveric
      study. METHODS: Four methods of tibial nail length determination were compared.
      Nail lengths for each of fourteen cadaveric lower extremities were determined
      using full-length scanograms, spotograms, acrylic template overlays, and the
      distance between the tibial tubercle and the medial malleolus (TMD). Each tibia
      was then nailed. The accuracy of each method was then evaluated. RESULTS: The
      full-length scanogram method resulted in incorrect nail lengths in eleven of
      fourteen (79 percent) cases. Six of fourteen (43 percent) incorrect nail lengths
      resulted from the use of spotograms. All measurements made with the Template
      technique yielded nails that were too short (100 percent). The TMD method
      rendered four of fourteen (29 percent) nails of incorrect size. CONCLUSION: The
      tibial tubercle-medial distance (TMD) proved an easy, inexpensive, and accurate
      method of preoperative nail assessment.

PMID- 10926243
TI  - Closed interlocking nailing of humeral shaft fractures with the Russell-Taylor
      nail.
AB  - OBJECTIVE: To assess the role of the Russell-Taylor humeral nail in the treatment
      of humeral shaft fractures. STUDY DESIGN: Retrospective with a mean radiologic
      and clinical follow-up at thirty-two months. SETTING: University teaching
      hospital. PATIENTS: Total of thirty-seven patients treated with the Russell
      Taylor humeral nail. INTERVENTION: All patients were treated with the Russell
      Taylor humeral nail inserted in an antegrade fashion. OUTCOME MEASURES:
      Radiologic union and shoulder function in terms of pain, power, range of
      movement, and activities of daily living. RESULTS: There were four established
      nonunions and four cases of delayed union (time to union > four months). Age of
      patient was the only predictor of nonunion. There was one infection and one
      intraoperative fracture. Two prominent proximal screws required removal, and one
      nail was removed after union because of impingement. Three patients required
      manipulation under anesthesia to improve shoulder movement. At review, six
      patients had residual poor shoulder function as per Constant score, four
      attributable to shoulder stiffness and two to residual pain. CONCLUSION: The
      authors' findings indicate a significant rate of delayed or nonunion in the
      elderly patient. When the high rate of union with conservative treatment is
      considered, the indications and rationale for intramedullary humeral nailing
      should be clearly defined.

PMID- 10926244
TI  - Results of acute excision of the radial head in elbow radial head fracture
      dislocations.
AB  - OBJECTIVES: To evaluate the results of radial head excision for the treatment of
      elbow fracture-dislocations with an unsalvageable comminuted radial head fracture
      and no other associated fractures. DESIGN: Retrospective study. SETTING:
      University Hospital. PATIENTS AND INTERVENTION: Ten elbow fracture-dislocations
      with a comminuted radial head fracture treated with radial head excision in our
      institution between 1990 and 1996 and followed a mean of 4.62 years. MAIN OUTCOME
      MEASUREMENTS: Clinical results were graded using the Mayo index and the
      Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire. Radiographs
      were evaluated for proximal radius migration, elbow angulation, degenerative
      changes, and ectopic bone. RESULTS: Final clinical results were excellent in four
      patients, good in five patients, and fair in one patient. Pain was absent in six
      patients, mild in three patients, and moderate in one patient. Mean flexion arc
      was 7.5 to 140 degrees, and mean pronation and supination were 85.5 and 83.5
      degrees, respectively. Average strength loss was 15 percent. No elbow was
      unstable. The raw DASH score ranged from 39 to 62 points (normalized values, 0.66
      to 15,79 points). On average, the carrying angle increased 5.4 degrees.
      Degenerative changes were absent in two, Grade I in four, and Grade II in four
      patients. Ectopic bone, mainly residual fracture fragments, was evident in four
      patients. Proximal migration of the radius averaged 1.6 millimeters; the two
      patients with over four millimeters of migration had mild wrist pain.
      CONCLUSIONS: Acute radial head excision for the treatment of elbow fracture
      dislocations provides satisfactory short-term clinical results when there are no
      other associated intraarticular fractures. However, the long-term significance of
      the early degenerative changes is not known.

PMID- 10926245
TI  - Evaluation of the syndesmotic screw in low Weber C ankle fractures.
AB  - OBJECTIVE: To determine the functional and radiographic outcome of low Weber C
      ankle fractures and to evaluate the contribution of the syndesmotic screw in
      their outcome. DESIGN: Prospective evaluation of a consecutive series. SETTING:
      Level I trauma center. PATIENTS: Forty-five patients divided into two groups
      matched for age, sex, and severity of injury. Twenty-six patients were treated
      with open reduction, internal fixation, and a supplemental syndesmotic screw, and
      nineteen patients were treated without a syndesmotic screw. Minimum time to
      follow-up was three years. METHODS: A subjective, objective, and radiographic
      ankle scoring system was used. Logistical regression analysis was performed to
      determine whether the presence or absence of a syndesmotic screw was a predictor
      of a poor outcome. The likelihood ratio test was used to evaluate the
      significance of each variable in both univariate and multivariate analyses.
      RESULTS: There was no statistically significant difference between either group,
      either using subjective outcome criteria (p = 0.86) or in ankle range of motion
      (p = 0.94). Logistical regression analysis indicated that fracture dislocation
      could be used as a predictor of a poor outcome for either group. Inadequate
      reduction and advancing age were also found to be significant predictors of a
      poorer outcome regardless of the use of a syndesmotic screw (p = 0.003, p =
      0.004). CONCLUSIONS: Judicious fixation of Weber C type injuries within five
      centimeters of the ankle joint, with or without a syndesmotic screw, gives
      similar results. Obligatory fixation of these fractures with syndesmotic screws
      appears to have no benefit and creates the need for an additional procedure.

PMID- 10926246
TI  - Retrograde nailing of femoral fractures distal to previous osteosynthesis.
AB  - As the proportion of elderly in the population grows, the incidence of femoral
      fractures distal to previous proximal osteosynthesis is increasing. When the gap
      between two rigid load-bearing fixations consists of osteopenic bone, the risk of
      further fractures increases. Herein the authors describe a load-sharing device
      that stabilizes the fracture and eliminates the osteopenic gap, allowing early
      mobilization and rapid return to the preinjury level of activity.

PMID- 10926247
TI  - Atlanto-occipital dislocation: a report of three patients and a review.
AB  - Traumatic atlanto-occipital dislocation is usually instantaneously fatal when it
      occurs. Survival is possible with minimal remaining neurologic deficits if
      diagnosed quickly and treated appropriately. The authors present three reports of
      patients who survived the incident, and they review the anatomy of the atlanto
      occipital joint, clinical presentation, diagnosis, and treatment of this
      traumatic injury.

PMID- 10926248
TI  - Flexor surface material.

PMID- 10926249
TI  - Multicenter trials.

PMID- 10926250
TI  - Acetabular fractures.

PMID- 10926251
TI  - External quality assessment survey for hematological laboratories in China.
AB  - To evaluate the feasibility of improving external quality assessment (EQA), we
      set up an experimental EQA survey that included 465 participants in China. During
      the period of this survey, we checked the quality of the EQA samples, divided the
      participants into different groups, each laboratory's result was assessed by
      calculation standard deviation index (SDI). The reference values were determined
      to evaluate the accuracy for peer groups. The data showed that the stability of
      the EQA samples was acceptable. Except for WBC count of the Abbott group, the
      mean, median and reference values for each parameter were very close. We found
      that the main reason affecting the performance of the participants was not using
      the reagents. calibrator and QC material recommended by manufacturer. From this
      survey, we obtain a good reference for future improvement.

PMID- 10926252
TI  - Country report: Clinical chemistry in Indonesia.
AB  - Seven hundred clinical laboratories in all over 27 provinces in Indonesia
      participated the Indonesian External Quality Assurance Scheme (Program Nasional
      Pemantapan Kualitas Laboratorium Kesehatan bidang Kimia Klinik). Among those
      laboratories, the government laboratory account for 288 (41%), and the rest 412
      (59%) are private laboratories. Automatic analyzer was used by approximately 22%
      of the participating laboratories. Seventeen analytes were included in the
      program: bilirubin, cholesterol, creatinine, glucose, total protein, urea, uric
      acid, triglycerides, AST, ALT, calcium, albumin, alkaline phosphatase, gamma-GT,
      sodium, potassium, and chloride. Using WHO scoring system, median overall VIS of
      128 was obtained. It means that the all over performance was fairly good .
      Bilirubin got the best median VIS (33). Sodium (median VIS 177), potassium (162)
      and chloride (209) got the worst VIS compared to the other parameters.

PMID- 10926253
TI  - Country report: the Indonesian NEQAS on hematology. National External Quality
      Assessment Scheme.
AB  - Around six hundred clinical laboratories in all the province of Indonesia
      participated the Indonesian National External Quality Assessment Scheme (NEQAS)
      on Hematology (Program Nasional Pemantapan Kualitas Laboratorium Klinik bidang
      Hematologi). Automated analyzer gave better results compared to the manual
      method. For hemoglobin, the CV of automated analyzer and manual method were 2.8%
      and 9.1%, respectively. The CV of automated analyzer and manual method for
      leukocyte count were 8.3% and 32.3%; for erythrocyte count were 9.7% and 80.8%;
      and for thrombocyte count were 10.3% and 45.9%. We observe no significant
      improvement of the overall performance from 1986 to 1998. Quality control
      material for NEQAS on hematology is still a problem. The artificial particles
      seem not behave exactly like the human cells (leukocytes, thrombocytes).

PMID- 10926254
TI  - Country reports from Japan: external quality assessment scheme in Japan.
AB  - Several external quality assessment schemes (EQAS) have been conducted in Japan.
      Results obtained from nation-scale EQAS reveal the current quality of laboratory
      testing in each laboratory. The largest nation-scale EQAS in Japan is that
      conducted by the Japan Medical Association. The numbers of participants and of
      items evaluated have increased in EQAS by JMA over its history of 32 years.
      Improvement in inter-laboratory differences has been observed for most items in
      EQAS in recent decades. In 1998, about 2,500 laboratories from throughout the
      country participated in this surveillance, and 47 items were evaluated. The
      coefficient of variations for the group of all participants was less than 5% for
      about one third of all test items. On the other hand, very high variations over
      20% were observed for 6 items. Also, inter-method differences exist for many
      items, which may be or may not be related to matrix effects. Retrospective
      evaluation of all EQAS data suggests that there is still room for improvement in
      inter-laboratory differences.

PMID- 10926255
TI  - Incidence of abnormalities in laboratory tests found in surveillance of adults
      over 40 years of age.
AB  - National health check-up systems have been used for 5 years in Japan for adults
      who are over 40 years of age. As part of a national project, Osaka prefecture is
      also conducting a program for health check-up testing and cancer screening for
      this age group. This surveillance revealed that incidence of obesity,
      hypertension, cholesterolemia, albuminuria, or abnormal ECG was high. Analysis of
      surveillance results should contribute to understanding the present status and
      recent trends in diseases in the aged. With continuation of this surveillance for
      a number of years, trends in life-style related diseases in Japan should be
      detectable.

PMID- 10926256
TI  - Twenty-years of experiences in external quality assurance in Korea.
AB  - The Korean External Quality Assurance Scheme (KEQAS) was set up by a voluntary
      organization, the Korean Society of Quality Control in Clinical Pathology (KSQC)
      in 1976. The KSQC was reorganized as the Korean Association of Quality Assurance
      for Clinical Laboratories (KAQACL) in 1991. The KAQACL is a government authorized
      organization. With the growing popularity of the KEQAS, its coverage has expanded
      to include ten disciplines, and the number of participants has grown to 470
      clinical laboratories by the end of 1998. The ten programs are: clinical
      chemistry, clinical microbiology, diagnostic hematology, diagnostic immunology.
      blood bank, urinalysis, immunoassay, TDM (therapeutic drug monitoring), inborn
      errors of metabolism and diagnostic genetics. KAQACL membership accreditation is
      based on the QAP return rate, of which the minimum criterion for acceptability is
      50%. Membership in KAQACL is highly regarded by the Inspection and Accreditation
      Program of the Korean Hospital Association and is an essential requirement for
      outreach services of commercial laboratories. While monitoring the quality of
      laboratory performances during the last two decades, the KEQAS has provided
      information on reliability of laboratory performances regarding methods,
      manufacturers and laboratory groups. The inter-laboratory coefficient variations
      (CVs) and the variance index score (VIS) have gradually decreased over the years,
      particularly during the 1990s. The participants who achieved good performances
      (less than 100 VIS) in clinical chemistry tests have gradually increased in
      number up to 83.2% of all participants.

PMID- 10926257
TI  - External quality assurance in Malaysia.
AB  - An activity supportive of the MOH QA Programme, the National EQAS for clinical
      chemistry monitors for analytical performance in core routine biochemical testing
      by the pathology laboratories, with unsatisfactory performance scores serving to
      alert against deficiencies or problems and the scores in subsequent challenges
      providing the feedback of effectiveness of remedial actions taken. While
      unacceptable individual analyte performance score (variance index score, VIS)
      indicated problems in instruments, reagent and calibrators, or the use of
      inherently poorer methods, repeated occurrence of unsatisfactory OMRVIS was
      traceable to generally poor laboratory management of usually inadequately
      equipment small laboratories. The outcome has been one of slow but gradual
      improvement in the overall performance of participating laboratories, with a move
      towards methods upgrading and standardization to achieve greater concordance of
      results. Presently, the programme is limited to 61 government and 4 private
      hospital laboratories in the country for 12 commonly assayed clinical
      biochemistry analytes. It is hoped that the NEQAS could be extended to the other
      private laboratories and that of academic institutions. However, this is
      dependent to a large extent on the manpower and financial support obtainable by
      the organizing body of the programme in the future. Belk and Sunderman, 1947
      demonstrated that laboratories participating in an quality assessment scheme
      could rapidly and dramatically improve their analytical performance. In some
      countries, participation has become mandatory, and acceptable performance is a
      requirement in laboratory accreditation. The need and value of the NEQAP is,
      therefore, evident. While there may be limitations in the national programme.
      efforts are being made at improving the programme within the means and resources
      of the organising body. The goals of the NEQAP are not just to monitor
      performance but also to educate. On this, matters related to and supportive of
      these goals have also been pursued. The annual workshop/forum on quality controls
      had allowed exchange of information between representatives of participating
      laboratories and the organising body. Recently in the 1997 MOH Quality
      Improvement evaluation, Quality Control has been evaluated together with the
      other 17 such activities. The study on knowledge, attitude and practice has
      provided the necessary feedback and will be used for future planning in making
      efforts at increasing the effectiveness and benefits of the all QC activities
      including this NEQAP for clinical chemistry. In addition, there is a need to look
      into areas such as selection of methods and test systems, and improvement of
      continuing education, training as well as research in quality improvement as
      suggested by the Quality Improvement evaluation.

PMID- 10926258
TI  - Quality assessment in clinical chemistry: a Thailand experience.
AB  - A Thailand quality assessment program called "The External Quality Assessment in
      Clinical Chemistry, EQAC" was found in 1986. Ablind lyophilized control serum is
      monthly-cycle distributed to the participants and the returned test-report values
      are evaluated by a computed program. Evaluated report Variance Index Scores (VIS)
      and grades of test and mean score of all tests are posted back to the
      participants including a back of "The Newsletter of the EQAC". The development
      has been indicated by an increasing number of active participants and an
      improvement due to decreasing Variance Index Scores. In 1998 the program was
      applied by 324 laboratory participants of which 59% of general hospital and
      community health hospital laboratory, 29% of private hospital laboratory
      including polyclinics, and 12% of the others. By now as many as 144 trials of 23
      biochemistry tests at different methods were assessed from the EQAC program.
      Participant communication, knowledge update and enhanced quality encouragement
      have been managed by mean of participants' VIS from 120 to 93 during 1987-1998.

PMID- 10926259
TI  - Effects of non-analytical factors on the quality of laboratory results.
AB  - The quality of clinical laboratory measurement is comprised of 2 phases, the
      analytical and non-analytical phases. Nowadays, a well established quality
      control system has been applied. However, the non-analytical phase is a state of
      the art that must be paid attention to. We studied the non-analytical (pre- and
      post-) factors. A questionnaire was distributed to 298 hospital laboratories whom
      participated in the External Quality Assessment Scheme in Clinical Chemistry
      (EQAC) program of Faculty of Medical Technology, Mahidol University. The
      respondent rate was 71%. Most of the responder was female with a bachelor degree
      in medical technology or equivalent, who was the chief of the laboratory. Results
      shows that patient preparation, patient identification, specimen acquisition,
      specimen handling, and documentary system (specimen recording and result
      reporting) were important consideration factors. The turnaround time was also a
      main issue. Verification of test results was an important process too. Finally,
      as a good laboratory practice, one must has the strategies to detect and
      eliminate the non-analytical errors.

PMID- 10926260
TI  - Thai clinical laboratory responsible to economic crisis.
AB  - Nowadays, Thailand encounters a serious economic crisis. A clear consensus has
      been made that a cost-saving system must be the important tool. Both private and
      government organizations are engaged in this situation. We studied the cost
      saving in the clinical laboratory. A questionnaire was distributed to 45 hospital
      laboratories located in Bangkok. Results showed that efforts to control the cost
      are the essential policy. There was a variety of factors contributing to the cost
      saving process. The usage of public utility, non-recycle material and unnecessary
      utility were reconsidered. Besides, capital cost (wages and salary) personnel
      incentive are assessed. Forty three of the 45 respondents had attempted to reduce
      the cost via curtailing the unnecessary electricity. Eliminating the needless
      usage of telephone-call. water and unnecessary material was also an effective
      strategy. A reduction of 86.9%, 80 % and 80.0% of the mentioned factors
      respectively, was reported. An inventory system of the reagent, chemical and
      supplies was focused. Most of the laboratories have a policy on cost-saving by
      decreased the storage. Twenty eight of the 45 laboratories considered to purchase
      the cheaper with similar quality reagents instead. And some one would purchase a
      bulky pack when it is the best bargain. A specific system "contact reagent with a
      free rent instrument" has been used widely (33.3%). Finally, a new personnel
      management system has been chosen. Workload has rearranged and unnecessary extra
      hour work was abandoned.

PMID- 10926261
TI  - A diversity of blood smear examination system of Thai public hospital.
AB  - A good laboratory practice is the heart of clinical laboratory quality. One must
      establish a standard system in order to achieve the quality. However, standard
      system is not only the technical but also a state of the art. The socioeconomic
      and culture are the influence factors. At present, technique of reporting the
      blood smear examination is still a nation controversy. We surveyed the blood
      smear examination reporting system of the public hospital in Thailand. There were
      77 hospitals participated in this study. A questionnaire comprised of 23
      questions was distributed to 105 clinical laboratory staffs of the public health
      hospitals. Results showed that there was a diversity of blood smear examination
      reporting system. Generally, there were 2 ways of blood smear review. Every
      smeared slide and only abnormal slides were re-examined by the conventional
      technique. When an abnormal white blood cell blood picture was observed. The
      presence of either blast cell or atypical lymphocyte has clinical significance. A
      majority of laboratory would report in form "counting number of abnormal cell
      within 100% of the differential count". For other abnormalities of white blood
      cell; i.e. the neutrophils with toxic granules, most of laboratory reported as
      "presence". Interestingly, the red blood cell reporting system varied from
      laboratory to laboratory. There was a total of nine reporting patterns. Results
      indicated that pattern 4 (few or some, 1+,2+,3+,4+ are 5-10%, 11-25%, 26-50%, 51
      75% and 51-100% cell/oil field, respectively) was the most popular one in
      reporting anisocytosis and poikilocytosis. However, the reporting pattern on red
      blood cell staining was difference. Pattern 4 and pattern 7 (grading by the size
      of central pallor) obtained a same popularity on the consideration of
      hypochromia. But the pattern 9 (few or some, 1+,2+,3+ are 0-1, 1-3, 4-6 and >6
      cell/oil field, respectively) was the most frequently used in reporting of
      polychromasia. Fortunately we found that the reporting system for platelet was
      not complicated. A majority of laboratory chose the qualitative pattern
      (reporting as adequate, increased and decreased). Our study indicated that Thai
      clinical laboratory encounter a diversity of blood smear reporting system. Every
      clinical laboratory should pay a great attention to this circumstance. Since a
      good laboratory practice is a knot of the knot-bolt system of healthcare service,
      therefore, a nation standard system must be established in the near future.

PMID- 10926262
TI  - External quality control study of lymphocyte subset tests in Japan.
AB  - We have evaluated external quality assurance of lymphocytes subset tests in
      Japan. The data suggest: 1) Values of lymphocyte subsets were variable at each
      medical laboratory in Japan. 2) Value of CD3 did not varied so much, but that of
      CD 19/20 or NK marker was widely varied. 3) Values of CD4 and CD8 varied in small
      extension. 4) CV of values was relatively low when analysis was carried out in
      commercial laboratories or when antibodies and instrument of Ortho-Clinical
      Diagnostics were used. 5) In some cases, CV was also relatively low if number of
      cell washing times was low or if self made lytic agents were used for cell
      lysing.

PMID- 10926263
TI  - Quality control in a manual and an automated leukocyte differential count.
AB  - Quality control (QC) has been introduced in laboratories, and QC surveys in
      leukocyte differential count to enhance quality have been performed by College of
      American Pathologists, Japanese Association of Medical Technologists, Osaka
      Medical Association and manufacturers. The results of QC survey in a manual
      leukocyte differential count indicated problems on the differentiation of
      segmented neutrophils and band neutrophils and the detection of pathological
      blood cells on blood smear. While the results of QC survey in an automated
      leukocyte differential count performed by same manufacturer with an automated
      blood cell counter were satisfactory, however, there was a difference in
      leukocyte differential cell counts among laboratories with other manufacturer's
      instruments because the synthetic blood material used in QC is an exclusive item
      for an instrument. It is necessary to further reeducate the medical technologists
      in order to improve morphological performance, and to standardize the synthetic
      blood material for compatibility with various automated blood cell counters.

PMID- 10926264
TI  - Quality control and quality assurance of platelet counting.
AB  - The accuracy and precision of platelet counting using new automated blood cell
      analyzers is satisfactory. However, there are several errors in automated
      platelet counting. Careful review of blood cell histograms and peripheral blood
      films is necessary to avoid false platelet counts as well as to ensure a good
      quality control regimen.

PMID- 10926265
TI  - Standardization of coagulation tests.
AB  - A lot of attempts have been made to standardise both activated partial
      thromboplastin time (APTT) and prothrombin time (PT). Only the standardization of
      PT has been successfully implemented while the standardization of APTT is still
      underway. The PT test is a common method for monitoring oral anticoagulant
      therapy. Owing to the variable response of the thromboplastins and the different
      ways of reporting, PT results obtained from patients treated with oral
      anticoagulants have not been interchangeable between laboratories. In 1977, the
      World Health Organization (WHO) designed a batch of human brain thromboplastin as
      the first international reference preparation (IRP) for thromboplastin and a
      calibration system was proposed in 1982, based on the assumption that a linear
      relationship exists between the logarithm of the PT obtained with the IRP and
      test thromboplastins. This calibration model is used to standardize the reporting
      of the PT by converting the PT ratio observed with the local thromboplastin into
      an International Normalized Ratio (INR). The INR system is being adopted by an
      increasing number of hospitals in many countries. With the increasing use of the
      INR system, a number of problems have been identified with the INR system. The
      most serious one is that the ISI of a thromboplastin depends on the coagulometer
      used. Besides, a number of investigators have noted that the ISI value provided
      by the manufacturer for each new batch of thromboplastin reagent may be incorrect
      and the use of inappropriate control plasma can lead to erroneous INR
      calculations. Four solutions have been proposed to solve the problems of the INR
      system as follows: (a) the local system calibration with lyophilized plasma
      calibrants with assigned manual PT determined in terms of the relevant IRP for
      thromboplastin; (b) the use of a mean normal prothrombin time (MNPT) obtained
      with the coagulometer to derive the prothrombin ratio: (c) PT standardization by
      means of the procedure using plasma calibrants: and (d) selection of sensitive
      thromboplastin with low ISI values. The INR system has been adopted in Thailand
      since 1984. There are 3 steps in the implementation as follows: (a) preparation
      of National Reference Thromboplastin; (b) selection of high sensitive
      thromboplastin; and (c) optimal therapeutic range for Thai patients. The
      anticoagulant effect of heparin is usually monitored by the APTT, a test that is
      sensitive to the inhibitory effects of heparin on thrombin, factor Xa. and factor
      IXa. However, the type of clot detection system, the contact activator; and the
      phospholipid composition of the reagent affect the APTT response. In 1995.
      ISTH/ICSH proposed a calibration model for APTT standardization. As the problem
      showed a great similarity to PT standardization, the same model of calibration
      was applied but no international reference preparation for the APTT is yet
      available. In 1998. van den Besselaar et al proposed a lyophilized APTT reagent
      comprising synthetic phospholipids and colloidal silica as a candidate IRP for
      the APTT.

PMID- 10926266
TI  - Hemostatic alterations in beta-thalassemia/hemoglobin E patients.
AB  - To search for evidence of coagulation activation ex vivo, the levels of human
      prothrombin fragment 1+2 (F1+2) were examined in 69 beta-thalassemia/Hb E
      patients. Levels of protein C inhibitor (PCI) and activated protein C - PCI
      (APC:PCI) complex were also determined in 9 of the above patients in conjunction
      with protein C (PC) antigen and activity, in an attempt to detect increased
      consumption of PC. In mean level of F1+2, there was a statistically significant
      difference between normal control and post-splenectomized patients (p < 0.05) but
      not between normal control and non-splenectomized patients (p > 0.05). The mean
      levels of PC activity and PC antigen in the patients were much lower than in
      normal controls. However, the mean levels of PCI and the mean level of APC:PCI
      complex in the patients were not significantly different from those in normal
      controls (p > 0.05). The high level of F1+2 in post-splenectomized patients found
      in this study agreed well with clinical and other laboratory findings. The normal
      level of PC inhibitor and APC:PCI complex found in this study provided no
      evidence of increased consumption of protein C in thalassemia patients.

PMID- 10926267
TI  - Standardization on laboratory diagnosis of thalassemia and abnormal hemoglobin.
AB  - Thalassemia is one of the most common single gene disorders. The geographic
      distribution of thalassemia and abnormal hemoglobin has been known for many
      years. A worldwide significant spread of these abnormal genes, especially from
      Southeast Asia, occurred in the last two decades. This has resulted in a dramatic
      increase of Hb E disorders and various Southeast Asian thalassemia genotypes,
      which means that requests for hemoglobinopathy investigations are likely to
      increase in many laboratories worldwide. Hemoglobinopathy screening and diagnosis
      may need to be undertaken antenatally, neonatally and in certain hematological
      situations. The introduction of automation for hemoglobinopathy screening,
      including the automated cell counting and HPLC system, is an important advance in
      technology for hematology laboratories. The instruments need to be calibrated and
      standardized to get an accurate data for interpretation. Internal and external
      control samples are also needed. Combination of test results is usually required
      to achieve a proper diagnosis, which in turn, provide a self-check for each
      laboratory test.

PMID- 10926268
TI  - Current status of liver function tests in Japan.
AB  - Inter-laboratory variations in data obtained from surveillance in Japan were
      studied. The items evaluated were related to liver function and were as follows:
      total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase
      (ALT), gamma-glutamyltransferase (gamma-GT), cholinesterase (CHE), lactate
      dehydrogenase (LD), alkaline phosphatase (ALP) and hepatitis markers. Inter
      laboratory coefficients of variations for bilirubin, AST and ALT were acceptable,
      being less than 10%. but higher variations were found for thle other enzyme
      assays. Detection of hepatitis markers was acceptable. However. even for
      parameters with lower inter-laboratory variation, differences in obtained values
      among different reagents or methods still existed. Thus, standardization will be
      needed for laboratory data in Japan, and this will contribute to international
      standardization in laboratory medicine in the future.

PMID- 10926269
TI  - External quality control results for hormones, tumor markers and CRP testing.
AB  - Most hormones, tumor markers, C-reactive protein, and rheumatoid factor (RF) are
      measured immunologically. Immunological methods based on the antigen-antibody
      reaction have certain specific problems, including their principle of
      determination, character of antibodies used, reaction conditions, and others.
      Free thyroxine (FT4) and thyroid stimulating hormone (TSH), as well as alpha
      fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate antigen,
      carcinoantigen 19-9 (CA 19-9), and CA 125 are very commonly measured in the
      routine medical laboratory. Authentic materials can be obtained for hormones and
      CRP, and efforts to improve quality control and standardization have been made
      for years. Results of surveillance for FT4, TSH, and AFP were not poor, but inter
      laboratory differences for CEA, CA 19-9, and RF were not insignificant.

PMID- 10926270
TI  - Quality control, quality assessment of laboratory tests, lipid profile.
AB  - The first external quality control survey implemented by the Japan Medical
      Association was performed in 1967, and now. 2.400 or more laboratories are
      participating in this survey. The survey for total cholesterol was performed from
      the first survey, triglyceride survey was started in 1973, and survey of HDL
      cholesterol was started in 1981. CVs of results for above items in the surveys
      were greatly improved after the 1980's. CVs in the 1970's were 8 to 10 per cent.
      but from the middle of the 1980's they were about 3 per cent or less. The main
      reason for this improvement is the introduction of automated analyzers in
      laboratories. An additional reason for this improvement is the requirement for
      accuracy of cholesterol determination by physicians, because the Japan Society of
      Atherosclerosis decided the consensus value of cholesterol for the initiation of
      treatment in 1987. Supply of standard material for cholesterol since 1995 is also
      a reason for this improvement. In 1995. CVs of cholesterol assays by were less
      than 3% when using most determination kits. Two determination kits, however, were
      found to give very high CVs. Both of them used dry chemistry, and the reason for
      these discrepancies was matrix effects of the survey material.

PMID- 10926271
TI  - Quality control, quality assessment of laboratory tests, HbA1c.
AB  - HbA1c level is known to be highly correlated with blood sugar level for a while
      after the maximum blood sugar level was observed, and is now considered more
      reliable than blood sugar as a long-term index of blood sugar control in diabetic
      patients. The Diabetes Control and Complication Trial in United States of America
      reported that mean HbA1c was the dominant predictor of retinopathy progression
      and that 10% lower HbA1c (e.g., 8 vs. 7.2 %) is associated with a 43 % to 45 %
      lower risk of progression of retinopathy. This report indicated that only a 1%
      difference in HbA1c level has a critical effect on progression of diabetic
      retinopathy. It also indicates the need for high precision and accuracy of
      hemoglobin A1c determination for control of diabetes patients. There are various
      methods to measure HbA1c. but now most laboratories use the high-performance
      liquid chromatography (HPLC) method; immunoassay is the second most popular,
      followed by affinity chromatography. It has been reported that each of these
      methods has its own characteristics, and that their results can vary
      considerably. In addition, there are two types of HbA1c, one a stable component
      and the other a labile component, and the measured HbA1c values were influenced
      by the contents of labile component included in the sample. The Japan Diabetes
      Society took a leading role and organized a committee on inter-laboratory
      standardization of HbA1c Determination in 1994. The HPLC method, which eliminates
      labile components, is used in most laboratories. Also, the number of laboratories
      using the immunoassay has gradually increased, while use of the other methods has
      rapidly decreased. In conclusion, since the proposal of a reference method and
      initiation of supply of reference materials by the Japan Diabetes Society, inter
      laboratory differences in measured values have become much smaller, mainly due to
      the methods used for measurements. We need to continue efforts toward further
      standardization of HbA1c determination.

PMID- 10926272
TI  - Compact dry chemistry instruments.
AB  - Compact dry chemistry instruments are designed for use in point-of-care-testing
      (POCT). These instruments have a number of advantages, including light weight,
      compactness, ease of operation, and the ability to provide accurate results in a
      short time with a very small sample volume. On the other hand, reagent costs are
      high compared to liquid method. Moreover, differences in accuracy have been found
      between dry chemistry and the liquid method in external quality assessment
      scheme. This report examines reagent costs and shows how the total running costs
      associated with dry chemistry are actually lower than those associated with the
      liquid method. This report also describes methods for minimizing differences in
      accuracy between dry chemistry and the liquid method. Use of these measures is
      expected to increase the effectiveness of compact dry chemistry instruments in
      POCT applications.

PMID- 10926273
TI  - Quality of dry chemistry testing.
AB  - Since the development of the qualitative test paper for urine in 1950s, several
      kinds of dry-state-reagents and their automated analyzers have been developed.
      "Dry chemistry" has become to be called since the report on the development of
      quantitative test paper for serum bilirubin with reflectometer in the end of
      1960s and dry chemistry has been world widely known since the presentation on the
      development of multilayer film reagent for serum biochemical analytes by Eastman
      Kodak Co at the 10th IFCC Meeting in the end of 1970s. We have reported test
      menu, results in external quality assessment, merits and demerits, and the future
      possibilities of dry chemistry.

PMID- 10926274
TI  - Quality control in urinalysis.
AB  - Quality control (QC) has been introduced in laboratories, and QC surveys in
      urinalysis have been performed by College of American Pathologist, by Japanese
      Association of Medical Technologists, by Osaka Medical Association and by
      manufacturers. QC survey in urinalysis for synthetic urine by the reagent strip
      and instrument made in same manufacturer, and by an automated urine cell analyser
      provided satisfactory results among laboratories. QC survey in urinalysis for
      synthetic urine by the reagent strips and instruments made by various
      manufacturers indicated differences in the determination values among
      manufacturers, and between manual and automated methods because the reagent
      strips and instruments have different characteristics, respectively. QC photo
      survey in urinalysis on the microscopic photos of urine sediment constituents
      indicated differences in the identification of cells among laboratories. From the
      results, it is necessary to standardize a reagent strip method, manual and
      automated methods, and synthetic urine.

PMID- 10926275
TI  - Reference methods in clinical chemistry.
AB  - For the measurements of analyses such as glucose, creatinine etc, in clinical
      chemistry, definitive methods and standard reference materials are available. On
      the other hand, for the measurements of the catalytic activity concentration of
      enzymes, various methods have been developed and those methods have generated a
      variety of results and reference ranges, difficulties in the interpretation of
      results, and difficulties in external quality assessment programs. Therefore, for
      the measurement of the catalytic activity of an enzyme, reference method is very
      important as the first start to obtain an accurate and precise result. We report
      the present situation of standardization for the measurement of the catalytic
      activity of enzymes and the comparison of reference methods including standards
      or consensus methods for the representative enzymes recommended by International
      Federation of Clinical Chemistry and the representative societies of clinical
      chemistry, and the survey results produced by Japan Medical Association.

PMID- 10926276
TI  - Specimen collection and handling.
AB  - Pre-analytical factors should be known and standardized to obtain reliable
      laboratory test result. If they could not be standardized they should be
      recognized. The specimen should be representative, properly collected, preserved,
      and labeled. It is also important to prevent any infection to the patients, the
      phlebotomists and the environment. The ideal is to get the right sample for the
      right test at the right time.

PMID- 10926277
TI  - Laboratory accreditation: quality in management and analysis and the input-output
      control.
AB  - An attempt to overcome the uncertainties and errors of all processes in clinical
      laboratory has been done in systematic ways. To reach the stage of laboratory
      accreditation, quality and standard criteria in the laboratory must be developed.
      Two aspects of quality are considered as management and analysis. Input-output
      control is proposed to handle the process from the beginning of laboratory design
      until post analytical phase or the control at the outcome. The model of ten Ms
      including model, material, machine, man, mind, money, method, mechanism,
      measurement and menace and one O or outcome, is elaborated to cover pre
      analytical, analytical and post-analytical phases. Laboratory accreditation is
      then an integral part of hospital accreditation with total quality management.

PMID- 10926278
TI  - Icsh activities and Asia.
AB  - The International Council for Standardization in Haematology (ICSH), an
      international organization promoting international agreement on hematological
      testing, is now restructuring to strengthen its activities. In Asia, a diversity
      of testing methods exists and the resulting testing levels make it difficult to
      compare test results internationally among Asian countries. Fortunately, the ICSH
      is considering regionalizing its organization to 5 sub-societies to increase its
      activity, and we have been able to establish a new society, ICSH-Asia, under the
      ICSH umbrella.

PMID- 10926279
TI  - Plan and process for hematology laboratory standard in Thailand.
AB  - In Thailand, there are around 2,000 clinical laboratories in private and
      government hospitals, By the end of year 2004, all of these laboratories are
      required to use the same or comparable standard nationwide. Many laboratories are
      in the process of starting ISO/IEC Guide 25 for the fulfillment of laboratory
      accreditation. To run the standard system of hematology laboratories in Thailand,
      we have considered three main aspects: standard in process, method selection and
      academic interpretation. Because of the wide spectrum of blood diseases in
      Thailand: thalassemia, iron deficiency anemia and G6PD deficiency hemolytic
      disease, the analysis and interpretation of laboratory results using different
      technology are of great importance. National plan has thus set up in two
      direction, one for standard process and another for academic approach.

PMID- 10926280
TI  - Field evaluation of who hemoglobin color scale in West Java.
AB  - The results obtained with a WHO hemoglobin (Hb) colour scale were evaluated in a
      field study in Chibubur district in Java island by comparison with hemoglobin
      values obtained by an automated blood cell analyzer K-800 (Sysmex. Kobe, Japan).
      When the color scale test was performed following the instructions for use. Hb
      values observed were usually higher than the values obtained by the analyzer.
      Thirty microl blood was loaded on the filter paper and an 60 sec waiting period
      was used. The sensitivity of results obtained with the color scale was 23.3%
      (14/60), and specificity was 96.6% (58/60). We propose an additional testing
      method based on our results.

PMID- 10926281
TI  - Hematology laboratory standardization: a plan for harmonization in Asia.
AB  - Hematology laboratory is generally required in the hospital. At the macroscale,
      hematology laboratories have served a large number of population. In Asia, more
      than 3,000 million people are potentially to use the hematology laboratory
      service, particularly the complete blood count. Since 1970s, automated technology
      has been introduced to Asia and as years passed by, technology diversity is
      increasing. However, there are considerable number of hematology laboratories
      that have no automated machine. They are still relied on manual technology which
      is still variable in spectrophotometer for hemoglobin determination, centrifuge
      for hematocrit and diluting pipet for cell counting. In particular, blood smear
      preparation and interpretation are very difficult to control for standardization
      from person to person and laboratory to laboratory. Different methodology and a
      large population in the huge geographical area in Asia, the agreement of standard
      criteria is greatly important. This report has shown strategy and action plan to
      reach the goal of hematology laboratory standardization in Asia.

PMID- 10926282
TI  - Cooperative work in medical testing between Thailand and Japan.
AB  - In order to exchange information on laboratory quality control, I was sent to
      Thailand for 74 days, as a representative of the Japan International Medical
      Technology Foundation in 1994. I visited Ayutthaya, Northern Thailand, Southern
      Thailand, Patthaya, and Bangkok and discussed quality control of laboratory
      testing with Thai laboratory staff. Information exchange has since continued
      between us.

PMID- 10926283
TI  - Genetic Predisposition to Neural Tube Defects?

PMID- 10926284
TI  - Erythropoietin therapy for premature infants: cost without benefit?

PMID- 10926285
TI  - Perinatal iron deficiency and the developing brain.

PMID- 10926286
TI  - Sudden infant death syndrome: a failure of compensatory cerebellar mechanisms?
AB  - The mechanisms underlying failure in sudden infant death syndrome may involve
      inadequate compensatory motor responses to a hypotensive challenge; the insult
      may result from a shock-like sequence, or from a ventilatory challenge that leads
      to a hypotensive event. Structures ordinarily not considered in mediating
      breathing or cardiovascular control, especially cerebellar-related structures,
      may play a critical role in compensatory responses, and underlie the position
      dependent risk for SIDS. Dysfunction in affected brain areas appears to arise
      prenatally from a compromised fetal environment, with a nicotinic component
      contributing to the deficient mechanism. Physiologic characteristics of infants
      who later succumb to SIDS, and cardiovascular events associated with the fatal
      scenario suggest a failure of interaction between somatomotor and autonomic
      control mechanisms in infants at risk for the syndrome. A failure of compensatory
      motor actions to overcome a profound hypotension, perhaps mediated by cerebellar
      mechanisms that regulate blood pressure, may underlie-the fatal event.

PMID- 10926287
TI  - Functional mitochondrial heterogeneity in heteroplasmic cells carrying the
      mitochondrial DNA mutation associated with the MELAS syndrome (mitochondrial
      encephalopathy, lactic acidosis, and strokelike episodes).
AB  - Most mitochondrial DNA (mtDNA) alterations associated with human disorders are
      heteroplasmic, i.e. mutant mtDNA molecules coexist with normal ones within the
      cell. We addressed the possibility of intermitochondrial exchanges through
      histologic analyses of cybrid clones with increasing proportion of the MELAS
      (A3243G) mtDNA transfer RNA point mutation. MtDNA-dependent cytochrome c oxidase
      activity and protein composition as well as mitochondrial membrane potential
      appeared heterogeneous in individual cells from clonal heteroplasmic cell
      populations on the basis of confocal and electron microscopy. The number of
      defective cells increased with increasing mutation load. We conclude that in the
      presence of a heteroplasmic mtDNA mutation in the cell type that we studied,
      intermitochondrial molecular exchanges cannot provide an efficient even
      distribution of the complementing molecules such as wild-type mtDNA, transfer
      RNA, or protein. Mitochondria in these heteroplasmic cells cannot, therefore, be
      considered a single functional unit.

PMID- 10926288
TI  - Heterozygosity for the common LCHAD mutation (1528g>C) is not a major cause of
      HELLP syndrome and the prevalence of the mutation in the Dutch population is low.
AB  - Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal
      recessive disorder of mitochondrial fatty acid oxidation. Apart from life
      threatening metabolic derangement with hypoketotic hypoglycemia, patients often
      show liver disease, cardiomyopathy, and neuropathy. A common mutation (1528G>C)
      in the gene coding for the alpha-subunit of the mitochondrial trifunctional
      protein harboring LCHAD activity is found in 87% of the alleles of patients.
      LCHAD is considered a rare disorder with only 63 patients reported in the
      literature. Whether this is due to a truly low prevalence of the disorder or
      because many patients remain unrecognized as a result of aspecific symptomatology
      is not clear. A remarkable association between LCHAD deficiency and the
      hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which is a
      severe complication of pregnancy, has been reported. Because of this, we studied
      the frequency of the common LCHAD mutation in the Dutch population by analyzing
      2,047 Guthrie cards and 113 women who had suffered from HELLP syndrome. To be
      able to perform this large-scale study in dried bloodspots, we developed a new
      sensitive PCR-restriction fragment length polymorphism method. The carrier
      frequency for the common LCHAD mutation in the Dutch population was found to be
      low (1:680), consistent with the observed low incidence of the disorder. In the
      group of women with a history of HELLP syndrome, the prevalence of the common
      LCHAD mutation was also low (1:113). We conclude that LCHAD deficiency is,
      indeed, a rare disorder and that heterozygosity for the common mutation is not a
      major cause of the HELLP syndrome.

PMID- 10926289
TI  - Effects of dexamethasone treatment on bone and collagen turnover in preterm
      infants with chronic lung disease.
AB  - Dexamethasone is used commonly in the treatment of chronic lung disease of
      prematurity, but there are concerns about possible deleterious effects on growth
      and bone. Our aim in this study was to examine the effects of dexamethasone
      treatment on bone and collagen turnover in preterm infants. Bone-specific
      alkaline phosphatase, the C-terminal propeptide of type I collagen (PICP,
      reflecting whole-body type I collagen synthesis), and the N-terminal propeptide
      of type III procollagen (P3NP, reflecting soft tissue collagen turnover),
      together with the C-terminal telopeptide of type I collagen (ICTP), urinary
      pyridinoline (Pyd), and deoxypyridinoline (all markers of collagen breakdown)
      were measured at weekly intervals over the first 12 wk of life in 14 preterm
      infants with chronic lung disease treated with dexamethasone. Results were
      expressed as SD scores relative to preterm control infants not treated with
      dexamethasone. PICP, P3NP, ICTP, and Pyd all showed marked decreases (-2.1 to 
      3.7 SD scores) during the first week of treatment (p < 0.001), returning to
      pretreatment levels after stopping dexamethasone. In the group as a whole, these
      collagen markers were negatively correlated with dexamethasone dose (p < 0.0001);
      negative correlations were also seen in most individual babies, although the
      slopes of individual regression lines varied by a factor of 2. Weight gain at 12
      wk was correlated with PICP, expressed as the mean SD score over 12 wk for each
      baby, (r = 0.69, p < 0.01) but not with other markers or cumulative dose of
      dexamethasone. We conclude that dexamethasone markedly suppressed collagen
      turnover in preterm infants in a dose-dependent fashion, although some babies
      were more affected than others. The degree of suppression of type I collagen
      synthesis was a strong independent predictor of overall weight gain over the
      first 12 wk of life.

PMID- 10926290
TI  - Proliferative response of different human osteoblast-like cell models to
      proinflammatory cytokines.
AB  - Children with inflammatory bowel disease are known to be at risk of osteopenia.
      The cause of this osteopenia is likely to be multifactorial, but the inflammatory
      process with its characteristic overproduction of cytokines has been implicated.
      To investigate this possible contribution of the disease activity to the
      development of osteopenia, we performed in vitro assays of the proliferation of
      osteoblast-like cells of differing origins in response to the inflammatory
      cytokines tumor necrosis factor-alpha and IL-1/beta. Osteoblast-like cells
      derived from pediatric bone explants, adherent stromal cells derived from bone
      marrow (osteoprogenitors), MG-63 osteosarcoma cells, and SV-40 virally
      transformed osteoprogenitor cells (HCC1) were studied. Tumor necrosis factor
      alpha stimulated the proliferation of cells in primary cultures (i.e. from
      explants and marrow samples) in a linear, dose-dependent manner. In contrast,
      inhibition of proliferation was observed with the established cell lines (MG-63
      and HCC1). IL-1beta stimulated proliferation of all cells apart from the
      immortalized human bone marrow cell line, HCC1, in which case potent inhibition
      was observed. We conclude that proinflammatory cytokines are potent regulators of
      osteoblast-like cell proliferation, and that the responses are specific to cell
      type. The opposite results obtained with established cell lines compared with the
      primary cultures suggest that careful consideration should be given to choosing
      the most suitable cell line for in vitro studies relating to in vivo mechanisms
      predisposing to osteopenia.

PMID- 10926291
TI  - Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in
      selected regions of neonatal rat brain.
AB  - Intrauterine growth retardation and diabetes mellitus during human gestation
      result in significant losses of fetal and neonatal brain iron. Brain iron
      deficiency is associated with impaired cognitive processes including memory and
      attention. The regional distribution of iron staining and cytochrome c oxidase
      (CytOx) activity have not been mapped in the iron-sufficient or -deficient
      neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative
      phosphorylation; its activity reflects neuronal metabolism. We hypothesized that
      neonatal brain iron deficiency differentially decreases iron and CytOx activity
      in brain regions, with more pronounced losses in structures involved in
      recognition memory. Pregnant Sprague Dawley rats were fed either an iron
      deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron
      staining and CytOx activity of 20 brain structures were mapped histochemically in
      25 rats from each group. Brain iron staining was reduced from 75% to 100% and
      CytOx staining was decreased from 0% to 42% in the iron deficient group (p <
      0.001). Areas with significantly reduced CytOx activity (p < 0.001) included all
      measured subareas of the hippocampus (CA1: 42%, CA3ab: 34%, CA3c: 33%, and
      dentate gyrus: 32%), the piriform cortex (17%), the medial dorsal thalamic
      nucleus (28%), and the cingulate cortex (41%). In contrast, the anterior thalamic
      nucleus, the lateral amygdaloid nucleus, and the medial habenula, areas not
      involved in higher cognitive functions, did not have significantly reduced CytOx
      activity (0%, 10%, and 16%, respectively). We conclude that perinatal iron
      deficiency differentially reduces neuronal metabolic activity, specifically
      targeting areas of the brain involved in memory processing.

PMID- 10926292
TI  - Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the
      rat brain.
AB  - Maternal caffeine intake has been suggested to influence the offspring. We have
      studied the effects of maternal caffeine intake on adenosine and GABA receptors,
      targets for caffeine, during development of the rat brain. Caffeine (0.3 g/L) was
      added to the drinking water of rat dams during pregnancy and early postnatal
      life. Adenosine A1 and A2A and GABAA receptor development was studied using
      receptor autoradiography and in situ hybridization. Pups were examined on
      embryonic d 14 (E14), E18, E21, 2 h after birth (P2h), P24h, postnatal d 3 (P3),
      P7, P14, and P21. Adenosine A, receptor mRNA was detected at E14 and receptors at
      E18. A1 mRNA levels increased from the level reached at E18 between P3 and P14
      (maximally a doubling), whereas A, receptors, studied by [3H]-1,3-dipropyl-8
      cyclopentyl xanthine binding, increased later and to a much larger extent (about
      10-fold) postnatally. Caffeine treatment had no significant effect on adenosine
      A1 receptors or on A1 receptor mRNA. A2A mRNA had reached adult levels by E18,
      whereas receptor levels were low or undetectable before birth and increased
      dramatically until P14. Caffeine did not influence A2A receptors or A2A receptor
      mRNA at any stage during development. [3H]-flunitrazepam binding, representing
      GABAA receptors, showed large regional variations during ontogeny, but there were
      no clear differences between the caffeine-exposed and the nonexposed pups. Thus,
      exposure to a low dose of caffeine during gestation and postnatal life had only
      minor effects on development of adenosine A, and A2A receptors and GABAA
      receptors in the rat brain.

PMID- 10926293
TI  - A human epithelium-specific vector optimized in rat pneumocytes for lung gene
      therapy.
AB  - Gene therapy vectors based on mammalian promoters offer the potential for
      increased cell specificity and may be less susceptible than viral promoters to
      transcription attenuation by host cytokines. The human cytokeratin 18 (K18) gene
      is naturally expressed in the lung epithelia, a target site for gene therapies to
      treat certain genetic pediatric lung diseases. Our original vector based on the
      promoter and 5' control elements of K18 offered excellent epithelial cell
      specificity but relatively low expression levels compared with viral promoters.
      In the present study, we found that adding a stronger SV40 poly(A) signal boosted
      primary rat lung epithelial cell expression but greatly reduced cell specificity.
      Addition of a 3' portion of the K18 gene to our vector as a 3' untranslated
      region (UTR) improved epithelial cell-specific expression by reducing expression
      in lung fibroblasts. The effect of the 3' UTR was not related to gross
      differences in cell-specific splicing. A deletion variant of this UTR further
      increased lung epithelial cell expression while retaining some cell specificity.
      These data illustrate the possibilities for using 3' UTR to regulate cell
      specific transgene expression. Our improved K18 vector should prove useful for
      pediatric lung gene therapy applications.

PMID- 10926294
TI  - Metabolic and functional response of neonatal pig hearts to the development of
      ischemic contracture: is recovery possible?
AB  - The potential for functional and metabolic recovery in neonatal hearts after the
      development of ischemic contracture remains controversial and undefined. This
      study documents post-ischemic recovery of metabolism and function in the in vivo
      neonatal heart after the development of onset and peak ischemic contracture. In
      piglets on cardiopulmonary bypass, hearts were reperfused after the development
      of either onset (TICo) or peak (TICp) ischemic contracture. Systolic (developed
      and systolic function, contractility) and diastolic (diastolic function,
      relaxation) performance was assessed throughout reperfusion. Biopsies were
      obtained at end-ischemia or end-reperfusion to assess metabolism. By end
      ischemia, the metabolic profiles of both TICo and TICp hearts confirmed energy
      store depletion and purine degradation that was quantitatively greater in TICp
      hearts. Hearts reperfused at TICo had consistent moderate impairment of developed
      function, contractility, diastolic function, and relaxation, whereas hearts
      reperfused at TICp had much more profound functional impairment. Diastolic
      function showed the worst functional recovery. In contrast, systolic function was
      not significantly altered in either study group and, thus, did not reflect the
      actual extent of injury. In addition, TICo hearts either did not further deplete
      or partially regenerated energy stores during reperfusion, whereas TICp hearts
      had further energy-store depletion and lactate accumulation. In summary, neonatal
      hearts reperfused after TICo maintained or partially restored energy stores and
      had significant but incomplete functional recovery. In contrast, further
      metabolic deterioration and profound functional impairment occurred with
      reperfusion after TICp, potentially indicating ongoing mitochondrial injury and
      compromised oxidative phosphorylation.

PMID- 10926295
TI  - Evidence of a role for local complement expression in a murine model of
      progressive glomerulonephritis.
AB  - C57/B6 mice received intraperitoneal horse spleen apoferritin (4 mg) with
      lipopolysaccharide (0.05 mg); control mice received 0.15 M NaCl. Control and
      treated animals were killed weekly for 6 wk; blood and urine specimens were
      obtained, and tissue samples were secured. Treated animals showed evidence of
      significant chronic disease, with proteinuria, hematuria, and uremia. A mild
      glomerulonephritis was present at 2 wk, with significant proliferative
      glomerulonephritis at 4 wk, progressing to chronic disease with
      tubulointerstitial changes at 6 wk. Changes at each time period were uniform
      between animals. C3 mRNA was first detected by in situ hybridization at 3 wk.
      Message was restricted to proximal tubular and periglomerular epithelial cells.
      Presence of C3 message preceded the development of interstitial inflammation and
      fibrosis by 1-2 wk, and its location and intensity paralleled the evolving
      interstitial disease. Although extensive mesangial C3 protein deposits appeared
      early, there was never C3 message in glomeruli or infiltrating cells. Before C3
      message became apparent, two cytokines known to up-regulate C3 transcription in
      vitro, IL-1 and IL-6, were detected by immunohistochemistry. The temporal
      sequence in this model is consistent with our hypothesis that local synthesis and
      activation of C3 in tubular epithelium is important to the interstitial component
      of chronic glomerulonephritis. The process is independent of the deposition of
      circulating complement in the glomerulus, but may be triggered by glomerular
      cytokines.

PMID- 10926296
TI  - Ontogeny of Na+/H+ antiporter activity in rat proximal convoluted tubules.
AB  - Neonates have a lower serum bicarbonate level than adults, which is caused by a
      lower renal threshold for bicarbonate. Eighty percent of bicarbonate reabsorption
      occurs in the proximal tubule, in which proton secretion is predominantly
      mediated by a luminal Na+/H+ antiporter. Previous studies have demonstrated that
      there is a maturational increase in apical membrane rabbit proximal convoluted
      tubule Na+/H+ antiporter activity. However, in rat brush border membrane
      vesicles, Na+/H+ activity was higher in neonates than that in adult rats. To
      examine the maturation of Na+/H+ antiporter activity in rat proximal convoluted
      tubules, we perfused rat proximal convoluted tubules in vitro. Na+/H+ antiporter
      activity was assayed as the proton secretory rate on luminal sodium removal.
      Na+/H+ antiporter activity was 121.2 +/- 18.4 pmol/mm x min in neonatal and 451.8
      +/- 40.6 pmol/mm x min in adult proximal convoluted tubules (p < 0.001). We next
      examined whether the increase in Na+/H+ antiporter activity was associated with
      changes in renal cortical NHE3 mRNA and brush border membrane NHE3 protein
      abundance. Adult renal cortical NHE3 mRNA abundance was 10-fold greater than that
      in 1-d-old neonates (p < 0.001). There was a comparable developmental increase in
      renal brush border membrane vesicle NHE3 protein abundance (p < 0.001). In
      summary, this study demonstrates that there is a maturational increase in rat
      apical membrane Na+/H+ antiporter activity, renal cortical NHE3 mRNA, and brush
      border membrane vesicle NHE3 protein abundance.

PMID- 10926297
TI  - Galactose metabolism by the mouse with galactose-1-phosphate uridyltransferase
      deficiency.
AB  - The ability of mice deficient in galactose-1-phosphate uridyltransferase (GALT)
      to metabolize galactose was determined in animals weaned to a mouse chow diet for
      a 4-wk period. When given [14C]galactose intraperitoneally, these animals slowly
      oxidized the sugar, excreting only 5.5% of the dose as 14CO2 in 4 h, whereas
      normal animals excreted 39.9%. These results mimic those seen in human
      galactosemic patients given isotopic galactose. When given 10 micromol of [1
      13C]galactose, normal animals excrete small amounts of labeled galactose and
      galactonate but no galactitol in urine whereas GALT-deficient mice excrete
      significant amounts of all of these as labeled compounds in urine. When
      challenged with galactose, only about 20% of the dose is excreted in urine, and
      even on the chow diet, significant amounts of galactose, galactonate, and
      galactitol are excreted in urine. These compounds are also found to be present in
      liver, kidney, and brain, except that galactonate is not found in brain.
      Galactose-1-phosphate accumulates in red blood cells to levels found in humans
      exposed to large amounts of galactose, and galactose-1-phosphate is found in
      increased amounts in liver, kidney, and brain of GALT-deficient animals. There
      was no difference in the hepatic concentration of uridine diphosphate galactose
      and uridine diphosphate glucose between normal and GALT-deficient mice. The
      explanation for the presence of galactose and its conversion products in tissues
      and urine of affected mice appears to be related to the presence of approximately
      1.75% of galactose-containing carbohydrates in the chow, which becomes
      bioavailable to mice. Despite the presence of galactose and its metabolites in
      tissues and urine and impaired ability to oxidize the sugar, the GALT-deficient
      animals are indistinguishable from normal animals and do not exhibit the
      phenotype of humans with GALT-deficiency galactosemia.

PMID- 10926298
TI  - Autonomic nervous system dysfunction in adolescents with postural orthostatic
      tachycardia syndrome and chronic fatigue syndrome is characterized by attenuated
      vagal baroreflex and potentiated sympathetic vasomotion.
AB  - The objective was to determine the nature of autonomic and vasomotor changes in
      adolescent patients with orthostatic tachycardia associated with the chronic
      fatigue syndrome (CFS) and the postural orthostatic tachycardia syndrome (POTS).
      Continuous electrocardiography and arterial tonometry was used to investigate the
      heart rate and blood pressure responses before and 3-5 min after head-up tilt in
      22 adolescents with POTS and 14 adolescents with CFS, compared with control
      subjects comprising 10 healthy adolescents and 20 patients with simple faint.
      Heart rate and blood pressure variability, determined baroreceptor function using
      transfer function analysis, and measured cardiac vagal and adrenergic autonomic
      responses were calculated using timed breathing and the quantitative Valsalva
      maneuver. Two of 10 healthy controls and 14 of 20 simple faint patients
      experienced vasovagal syncope during head-up tilt. By design, all CFS and POTS
      patients experienced orthostatic tachycardia, often associated with hypotension.
      R-R interval and heart rate variability were decreased in CFS and POTS patients
      compared with control subjects and remained decreased with head-up tilt. Low
      frequency (0.05-0.15 Hz) blood pressure variability reflecting vasomotion was
      increased in CFS and POTS patients compared with control subjects and increased
      further with head-up tilt. This was associated with depressed baroreflex transfer
      indicating baroreceptor attenuation through defective vagal efferent response.
      Only the sympathetic response remained. Heart rate variability declined
      progressively from normal healthy control subjects through syncope to POTS to CFS
      patients. Timed breathing and Valsalva maneuver were most often normal in CFS and
      POTS patients, although abnormalities in select individuals were found. Heart
      rate and blood pressure regulation in POTS and CFS patients are similar and
      indicate attenuated efferent vagal baroreflex associated with increased vasomotor
      tone. Loss of beat-to-beat heart rate control may contribute to a destabilized
      blood pressure resulting in orthostatic intolerance. The dysautonomia of
      orthostatic intolerance in POTS and in chronic fatigue are similar.

PMID- 10926299
TI  - Further evidence for genetic heterogeneity in familial hemophagocytic
      lymphohistiocytosis (FHLH).
AB  - Familial hemophagocytic lymphohistiocytosis (FHLH; MIM #267700) is an autosomal
      recessive disorder of immune regulation characterized by fever,
      hepatosplenomegaly, and cytopenia that is fatal without bone marrow
      transplantation. Recent studies have suggested the existence of FHLH loci at
      9q21.3-22 and t0q21-22 in Asian and European/African/Australian families,
      respectively. We studied two unrelated Canadian families in which first cousins
      were affected with FHLH. In an effort to localize the causative gene, we
      completed a genome-wide screen for homozygosity by descent by using an automated
      system to genotype 400 highly polymorphic dinucleotide repeat markers covering
      the genome with an average resolution of 10 centiMorgans (cM). We identified a
      total of three candidate loci that met the combined criteria for homozygosity by
      descent in one family and shared maternal alleles in the other family. One of
      these, D9S1690, had a cytogenetic localization (9q22.33) proximal to a previously
      reported inversion of chromosome 9 in an FHLH patient. However, additional
      closely linked flanking markers within 1-2 cM of all three candidates did not
      conform to the criteria for linkage in either family. Similarly, we excluded the
      linked 9q21.3-q22 and 10q21-22 regions recently reported in Asian and
      European/African/Australian families, respectively. The two families were then
      analyzed independently to encompass the possibility that they were segregating
      separate genes. Six additional candidate loci were identified on the basis of
      homozygosity for the same allele in all affected members of one family, but
      further analysis of closely linked flanking markers did not demonstrate similar
      homozygosity. Our data provide further evidence of genetic heterogeneity in FHLH
      and suggest the existence of at least a third locus for this disease.

PMID- 10926300
TI  - Glucosylsphingosine accumulation in mice and patients with type 2 Gaucher disease
      begins early in gestation.
AB  - Gaucher disease, the most common of the sphingolipidoses, results from the
      inherited deficiency of the enzyme glucocerebrosidase (EC 3.2.1.45). Although
      type 2 (acute neuronopathic) Gaucher disease is associated with rapidly
      progressive and fatal neurologic deterioration, the pathophysiologic mechanisms
      leading to the neurologic symptoms and early demise remain uncharacterized. While
      the pathology encountered in Gaucher disease has been attributed to
      glucocerebroside storage, glucosylsphingosine (Glc-sph), a cytotoxic compound,
      also accumulates in the tissues. Elevations of brain Glc-sph have been reported
      in patients with types 2 and 3 Gaucher disease. In this study, Glc-sph levels
      were measured using HPLC in tissues from mice with type 2 Gaucher disease created
      with a null glucocerebrosidase allele. Compared with unaffected littermates,
      homozygous mice with type 2 Gaucher disease had approximately a 100-fold
      elevation of Glc-sph in brain, as well as elevated levels in other tissues. This
      accumulation was detected in utero by E 13 and increased progressively throughout
      gestation. Similarly, elevated Glc-sph levels were seen in human fetuses with
      type 2 Gaucher disease, indicating that therapy initiated after birth may be too
      late to prevent the sequelae of progressive neurologic damage that begins early
      in gestation. These findings suggest that the accumulation of Glc-sph may be
      responsible for the rapid demise of mice with type 2 Gaucher disease and the
      devastating clinical course seen in patients with type 2 Gaucher disease.

PMID- 10926301
TI  - Comparative response in growth and bone status to three dexamethasone treatment
      regimens in infant piglets.
AB  - The objectives of this study were 1) to determine whether a zenith in bone
      formation (indicated by circulating osteocalcin) existed at night in early life,
      and 2) to compare the effects of three different dexamethasone (DEX) treatment
      regimens on bone turnover, bone mineral content, and growth. Three DEX treatment
      regimens were tested in 8-d-old piglets (n = 8/group): 1) low evening dose of DEX
      (0.5 mg/kg/d) as 70% in the morning and 30% in the evening for 10 d; 2) tapering
      course of DEX (0.5, 0.3, and 0.2 mg/kg/d) as 50% in the morning and 50% in the
      evening for 14 d; and 3) constant dose of DEX (0.5 mg/kg/d) as 50% in the morning
      and 50% in the evening for 10 d. Oral water placebo groups were tested with the
      same time courses. At pretreatment, plasma osteocalcin was significantly higher
      (p < 0.05) at 0100 than at 0900 and 1700. At necropsy, measures for DEX groups
      were calculated as Z-scores using values from the placebo groups. The low evening
      DEX dose led to a significantly lower reduction in plasma osteocalcin compared
      with the tapered and constant dosing regimens (p < 0.05). The significant weight.
      reduction in the DEX group occurred at d 9 in the low evening dose regimen but at
      d 7 in the constant dosing regimen, compared with the placebo group. Bone mineral
      content Z-score was reduced similarly in all DEX-treated groups across the three
      dosing regimens. We conclude that a plasma osteocalcin zenith at night exists in
      early life. A high DEX dose in the morning and low DEX dose in the evening may
      partially attenuate corticosteroid-induced suppression of bone formation and
      growth restriction.

PMID- 10926302
TI  - Circulating GH isoforms and GH bioactivity in preterm neonates.
AB  - Among the molecular variants of human GH, the monomeric 22-kD is the predominant
      isoform, whereas the 20-kD is the second most abundant isoform. Because little is
      known on the pattern of human GH isoforms in the early postnatal period, we
      evaluated serum levels of 22-kD GH by an immunofluorometric assay and of 20-kD GH
      by an ELISA using an anti-20-kD antibody, and measured GH bioactivity with the
      Nb2 cell bioassay in 19 preterm neonates (gestational age, 32 +/- 0.5 wk; mean +/
      SEM) on the fourth and 15th days of life. As control subjects, we studied 19
      full-term neonates (gestational age, 39 +/- 0.3 wk) on the fourth day of life and
      20 healthy adults, aged 20 +/- 0.3 y. Four-day-old preterm neonates showed
      significantly higher serum values of 20-kD GH (0.99 - 0.14 ng/mL) than full-term
      neonates (0.33 +/- 0.07 ng/mL; p < 0.001) and adults (0.09 +/- 0.02; p < 0.0001).
      Likewise, 22-kD GH and GH levels by Nb2 cell bioassay were also significantly
      higher (p < 0.001) in preterm than in full-term neonates and young adults. A
      significant decrease (p < 0.01) in 20-kD, 22-kD, and Nb2-determined GH was
      observed in preterm neonates on the 15th day of life The percentage of the 20-kD
      isoform was similar in the preterm infants at the fourth and 15th day, in full
      term-infants, and in adults (2.7%, 2.7%, 2.8%, and 3.16%, respectively). Our
      results indicate that 20-kD GH serum levels change throughout life as regards
      total amount, but not as regards percentage.

PMID- 10926303
TI  - Increased plasma beta-hydroxybutyrate, preserved cerebral energy metabolism, and
      amelioration of brain damage during neonatal hypoxia ischemia with dexamethasone
      pretreatment.
AB  - Dexamethasone (DEX) pretreatment has been shown to be neuroprotective in a
      neonatal rat model of hypoxia ischemia (HI). The exact mechanism of this
      neuroprotection is still unknown. This study used 31P nuclear magnetic resonance
      spectroscopy to monitor energy metabolism during a 3-h episode of HI in 7-d-old
      rat pups in one of two groups. The first group was pretreated with 0.1 mL saline
      (i.p.) and the second group was treated with 0.1 mL of 0.1mg/kg DEX (i.p.) 22 h
      before HI. Animals pretreated with DEX had elevated nucleoside triphosphate and
      phosphocreatine levels during HI when compared with controls. Saline-treated
      animals had significant decreases in nucleoside triphosphate and phosphocreatine
      and increases in inorganic phosphate over this same period. 31P nuclear magnetic
      resonance data unequivocally demonstrate preservation of energy metabolism during
      HI in neonatal rats pretreated with DEX. Animals pretreated with DEX had little
      or no brain damage following 3 h of HI when compared with matched controls, which
      experienced severe neuronal loss and cortical infarction. These same pretreated
      animals had an increase in blood beta-hydroxybutyrate levels before ischemia,
      suggesting an increase in ketone bodies, which is the neonate's primary energy
      source. Elevation of ketone bodies appears to be one of the mechanisms by which
      DEX pretreatment provides neuroprotection during HI in the neonatal rat.

PMID- 10926304
TI  - Abnormalities in zinc homeostasis in young infants with cystic fibrosis.
AB  - Low plasma zinc concentrations have been reported in approximately 30% of young
      infants with cystic fibrosis identified by newborn screening. The objective of
      this study was to examine zinc homeostasis in this population by application of
      stable isotope methodology. Fifteen infants with cystic fibrosis (9 male, 6
      female; 7 breast-fed, 8 formula-fed) were studied at a mean (+/-SD) age of 1.8 +/
      0.7 mo. On d 1, 70Zn was administered intravenously, and 67Zn was quantitatively
      administered with all human milk/formula feeds during the day. Three days later,
      a 3-d metabolic period was initiated, during which time intake was measured and
      complete urine and fecal collections were obtained. Fractional zinc absorption,
      total absorbed zinc, endogenous fecal zinc, and net absorbed zinc were measured;
      fecal fat excretion was also determined. Fractional absorption was significantly
      higher for the breast-fed infants (0.40 +/- 0.21) compared with the formula-fed
      group (0.13 +/- 0.06) (p = 0.01), but with the significantly higher dietary zinc
      intake of the formula-fed group, total absorbed zinc was higher for those
      receiving formula (p = 0.01). In 1 infants with complete zinc metabolic data,
      excretion of endogenous zinc was twofold greater for the formula-fed infants (p <
      0.05); net absorption (mg zinc/d) was negative for both feeding groups: -0.04 +/-
      0.52 for breast-fed; -0.28 +/- 0.57 for formula-fed. Endogenous fecal zinc losses
      correlated with fecal fat excretion (r = 0.89, n = 9, p = 0.001), suggesting
      interference with normal conservation of endogenously secreted zinc. These
      findings indicate impaired zinc homeostasis in this population and suggest an
      explanation for the observations of suboptimal zinc status in many young infants
      with cystic fibrosis prior to diagnosis and treatment.

PMID- 10926305
TI  - Heroin overdose deaths--Multnomah County, Oregon, 1993-1999.
AB  - In the United States, heroin use is increasing and was implicated in 3805 deaths
      in 1993 (1). Multnomah County is Oregon's most populous county (1998 estimated
      population: 641,900); three fourths of county residents live in Portland. In
      1999, in response to community concerns, the Multnomah County Health Department
      analyzed medical examiner (ME) data for 1993-1999 and interviewed heroin users to
      characterize heroin overdose deaths (HODDs) in the county. This report summarizes
      the findings of these studies, which indicate that HODDs in the county more than
      doubled from 1993 to 1999 (from 46 to 111), and that interviews with users helped
      identify possible public health interventions.

PMID- 10926306
TI  - Unintentional opiate overdose deaths--King County, Washington, 1990-1999.
AB  - Heroin and other opiates are central nervous system depressants; in an opiate
      overdose, respiration slows, potentially resulting in hypoxia, coma, or death. In
      1998, 140 deaths from unintentional opiate overdoses occurred in King County
      (which includes Seattle). To characterize these deaths, public health staff
      analyzed medical examiner data during 1990-1999. This report summarizes the
      results of that analysis, which indicate that the annual number of opiate
      overdoses increased 134% (from 47 to 110) and the county population increased
      11.3% (1998 estimated population: 1.7 million).

PMID- 10926307
TI  - West Nile virus activity--New York and New Jersey, 2000.
AB  - In late August 1999, an outbreak of encephalitis caused by West Nile virus (WNV)
      was detected in New York City and subsequently identified in neighboring counties
      (1). In response, an extensive mosquito-control and risk-reduction campaign was
      initiated, including aerial and ground applications of mosquito adulticides
      throughout the affected areas. No human WNV infections were found in New York
      City with an onset date after the campaign was completed. Cases continued to
      occur among humans in surrounding counties that did not undertake mosquito
      control efforts until later, suggesting that the campaign may have reduced human
      risk. In May 2000, CDC issued guidelines to direct national surveillance,
      prevention, and control efforts (2) and provided funds to support these efforts
      in 19 state and local health departments where WNV transmission had occurred or
      where transmission would probably occur based on known bird migration patterns.
      This report presents the findings of surveillance activities.

PMID- 10926308
TI  - Update: expanded availability of thimerosal preservative-free hepatitis B
      vaccine.
AB  - Thimerosal, a mercury-based compound, is no longer used as a preservative in any
      of the pediatric hepatitis B vaccines licensed in the United States. On March 28,
      2000, SmithKline Beecham Biologicals (Rixensart, Belgium) received approval from
      the Food and Drug Administration of a supplement to its hepatitis B license to
      include the manufacture of single-antigen, preservative-free hepatitis B vaccine
      (Engerix-B, pediatric/adolescent); distribution of this product has begun. A
      single-antigen, preservative-free hepatitis B vaccine (Recombivax HB, pediatric)
      from Merck Vaccine Division (West Point, Pennsylvania) had earlier received
      similar approval (1). A preservative-free Haemophilus influenzae type b
      (Hib)/hepatitis B combination vaccine (Comvax) from Merck Vaccine Division also
      is available. An adequate supply of preservative-free hepatitis B vaccine is
      available for all infant and childhood vaccinations. Thimerosal preservative
      containing hepatitis B vaccines may continue to be used for vaccination of
      adolescents and adults as recommended (2).

PMID- 10926309
TI  - Clinical efficacy of new thiazolidinediones and glinides in the treatment of type
      2 diabetes mellitus.
AB  - A central finding of the UKPDS was that in type 2 diabetic patients, tight
      glycemic control with HbA1c targets as close to the normal range as possible must
      be achieved to further reduce diabetes related-complications, -mortality, and 
      cardiovascular disease, highlighting the need for new, optimized treatment
      strategies. With a focus on clinical efficacy, this paper discusses the results
      from the 20 major therapeutical trials published in the years 1997-1999, that
      evaluated the new insulinsensitizing thiazolidinediones Rosiglitazone and
      Pioglitazone and the new insulin-releasing potassium channel blockers Repaglinide
      and Nateglinide. While for Nateglinide, promising, but only preliminary data is
      available at current, Rosiglitazone, Pioglitazone, and Repaglinide have been
      shown appropriate for both mono- and combination therapy with current standard
      drug treatment of type 2 diabetes. Similar to the known, older antidiabetic
      drugs, the new agents discussed have comparable blood glucose lowering potentials
      with a dose-related capacity of 0.5 to 1.5% HbA1c reduction. These beneficial
      effects were both seen in drug-naive patients previously treated with diet only
      and in combination therapies where patients had previous antidiabetic standard
      drug treatment suggesting effectiveness of glitazones and glinides also in more
      advanced stages of the disease. Problems with adverse effects appeared minor
      although long-range implications of weight gain, edema, lowering of hemoglobin,
      increase of total cholesterol for the glitazones, and hypoglycemia for glinides
      warrant further consideration. What becomes clear from the variety of most recent
      mono- and combination treatment studies with as much as five different classes of
      antidiabetic drugs is that individually tailored therapies that recognize quality
      of life parameters and target the predominant features of metabolic pathology
      (such as early postprandial versus fasting hyperglycemia, degree of insulin
      resistance, progressive loss of 1-cell function) may become a feasible goal in
      the future.

PMID- 10926310
TI  - Serum levels of substance P are decreased in patients with type 1 diabetes.
AB  - Morphological and immunohistochemical studies in diabetic subjects have shown a
      depletion of the neuropeptide substance P (SP) in the central and peripheral
      nervous system. This is the first study investigating serum levels of substance P
      in type 1 diabetes patients (n=50) and controls (n=75) by means of an enzyme
      immunoassay. The serum level of SP was significantly decreased in the diabetic
      group compared to the control group (10.12+/-0.29 vs. 12.25+/-0.38 pg/ml;
      p<0.0001). In diabetic patients, there was no correlation of substance P levels
      with age, serum creatinine, albuminuria, total cholesterol, HDL- or LDL
      cholesterol, triglycerides, HbA1c, type or duration of diabetes and gender.
      Furthermore, there was no difference in serum levels of SP in patients with or
      without retinopathy, but SP was significantly decreased in patients with
      neuropathy (9.59+/-0.48 vs. 10.78+/-0.83 pg/ml; p=0.04). These data show that SP
      is decreased in serum of type 1 diabetes patients, especially in those with
      diabetic neuropathy. Subsequent and already ongoing prospective studies in well
      validated diabetic patients with neuropathy may characterize the impact of this
      neurogenic marker in the course of diabetic neuropathy.

PMID- 10926311
TI  - Effects of alpha-lipoic acid on microcirculation in patients with peripheral
      diabetic neuropathy.
AB  - Diabetic polyneuropathy is a serious complication in patients with diabetes
      mellitus. In addition to the maintenance of a sufficient metabolic control, alpha
      lipoic acid (ALA) (Thioctacid, Asta Medica) is known to have beneficial effects
      on diabetic polyneuropathy although the exact mechanism by which ALA exerts its
      effect is unknown. In order to study the effect of ALA on microcirculation in
      patients with diabetes mellitus and peripheral neuropathy one group of patients
      (4 female, 4 male, age 60+/-3 years, diabetes duration 19+/-4 years, BMI 24.8+/
      1.3 kg/m2) received 1200 mg ALA orally per day over 6 weeks (trial 1). A second
      group of patients (5 female, 4 male, age 65+/-3 years, diabetes duration 14+/-4
      years, BMI 23.6+/-0.7 kg/m2) was studied before and after they had received 600
      mg ALA or placebo intravenously over 15 minutes in order to investigate whether
      ALA has an acute effect on microcirculation (trial 2). Patients were investigated
      by nailfold video-capillaroscopy. Capillary blood cell velocity was examined at
      rest and during postreactive hyperemia (occlusion of the wrist for 2 minutes, 200
      mmHg) which is a parameter of the perfusion reserve on demand. The oral therapy
      with ALA resulted in a significant decrease in the time to peak capillary blood
      cell velocity (tpCBV) during postocclusive hyperemia (trial 1: 12.6+/-3.1 vs
      35.4+/-10.9 s, p<0.05). The infusion of ALA also decreased the tpCBV in patients
      with diabetic neuropathy (trial 2: before: 20.8+/-4,5, ALA: 11.74+/-4.4, placebo:
      21.9-5.0 s, p<0.05 ALA vs both placebo and before infusions) indicating that ALA
      has an acute effect on microcirculation. Capillary blood cell velocity at rest
      (rCBV), hemodynamic parameters, hemoglobinA1c and local skin temperature remained
      unchanged in both studies. These results demonstrate that in patients with
      diabetic polyneuropathy ALA improves microcirculation as indicated by an
      increased perfusion reserve on demand. The observed effects are apparently acute
      effects. With the restriction of the pilot character of this investigation the
      findings support the assumption that ALA might exert its beneficial effects at
      least partially by improving microcirculation which is likely to occur also at
      the level of the vasa nervorum.

PMID- 10926312
TI  - Increased intracellular generation of reactive oxygen species in mononuclear
      leukocytes from patients with diabetes mellitus type 2.
AB  - Since increased cellular production of reactive oxygen species is a source of
      oxidative stress and thus may contribute to the development of diabetic
      complications, the baseline and stimulated concentrations of intracellular
      reactive oxygen species were measured in 16 patients with diabetes mellitus type
      2 and 19 healthy control subjects. Reactive oxygen species and cytosolic calcium
      were monitored spectrophotometrically using dihydrorhodamine-123 and fura-2,
      respectively, in a suspension of mononuclear leukocytes. Measurements were made
      in the presence or absence of superoxide dismutase, sodium azide, genistein, or
      bisindolylmaleimide 1. Baseline reactive oxygen species concentrations were
      significantly higher in diabetic patients compared with control (p<0.001).
      Activation of mononuclear leukocytes by formyl-Met-Leu-Phenylalanine and
      phytohemagglutinin significantly increased reactive oxygen species in diabetic
      patients compared with control (p<0.05). The formyl-Met-Leu-Phenylalanine-induced
      increases were unchanged in the presence of superoxide dismutase, but dropped
      significantly in the presence of sodium azide by 80% and 73% in diabetic patients
      and control, respectively (each p<0.01). The formyl-Met-Leu-Phenylalanine-induced
      responses were significantly inhibited by genistein and bisindolylmaleimide 1
      (p<0.01), suggesting the involvement of tyrosine kinase and protein kinase C.
      Resting calcium (p<0.05) and stimulated calcium were significantly greater in
      diabetic patients than in control. The results show that patients with diabetes
      mellitus type 2 generate increased reactive oxygen species under stimulated
      conditions, suggesting increased risk for oxidative stress and associated
      complications.

PMID- 10926313
TI  - Autoantibodies against autonomic nervous tissues in type 2 diabetes mellitus: no
      association with cardiac autonomic dysfunction.
AB  - There is evidence that autoimmune factors contribute to the pathogenesis of
      cardiac autonomic dysfunction in Type 1 Diabetes mellitus (DM). To evaluate the
      presence of autoantibodies against autonomic nervous tissues in Type 2 DM, 127
      patients were studied for complement-fixing sympathetic and parasympathetic
      ganglia (CF-SG and CF-PSG) autoantibodies with an indirect immunofluorescence
      technique. Five cardiac reflex tests were performed to investigate cardiac
      autonomic neuropathy. QTc interval was assessed in all patients. As a control
      group, 60 healthy non-diabetic subjects were also tested for CF-SG and CF-PSG
      autoantibodies. CF-SG autoantibodies were detected in 11 (9%) and CF-PSG
      autoantibodies were observed in 7 (6%) Type 2 DM patients, whereas in control
      subjects, the frequency was 1 (2%) and 0 (0%) respectively (ns vs. Type 2 DM
      patients). In Type 2 DM patients with cardiac autonomic neuropathy (n=31, 24%),
      CF-SG autoantibodies and CF-PSG autoantibodies were detected in 3 (10%) patients,
      respectively, compared to 8 (8%) and 4 (4%) in Type 2 DM patients without cardiac
      autonomic neuropathy (n=96, 76%, ns v. Type 2 DM with cardiac autonomic
      neuropathy). Both CF-SG autoantibodies and CF-PSG autoantibodies were observed in
      2 (7%) Type 2 DM patients with cardiac autonomic neuropathy and 3 (3%) Type 2 DM
      patients without cardiac autonomic neuropathy. Type 2 DM patients with cardiac
      autonomic neuropathy demonstrated a longer QTc-interval (446+/-42 ms) than Type 2
      DM patients without cardiac autonomic neuropathy (413+/-45 ms, p=0.0001). In Type
      2 DM patients with a prolonged QTc-interval (>440 ms: n=29, 23%), 2 (7%) patients
      presented with CF-SG and 3 (10%) had CF-PSG autoantibodies. In Type 2 DM, CF-SG
      and CF-PSG autoantibodies are not frequently observed. The results do not give
      evidence, that immunological factors--like in Type 1 DM--play a role in the
      pathogenesis of cardiac autonomic dysfunction in Type 2 DM.

PMID- 10926314
TI  - Major depression and impaired glucose tolerance.
AB  - Hypercortisolism is a frequent endocrine sign in major depression and cortisol is
      a well-known anti-insulinergic hormone. Impaired oral glucose tolerance has
      already been described in major depression. However, thus far no information is
      available on spontaneous, circadian insulin secretion in patients. We studied 26
      depressed inpatients along with 33 age- and sex-matched controls. Blood samples
      were collected at 30-minute intervals over a period of 26 hours (h) for
      estimation of cortisol, insulin and glucose. No differences in 24 h mean-insulin
      and glucose concentrations were detectable despite significantly reduced caloric
      consumption in patients. At the second morning a strictly standardized test meal
      of 2125 kjoule was given. Insulin and glucose responses to the test meal were
      significantly increased in hypercortisolemic patients compared to controls.
      Hence, patients with major depression have an impaired insulin sensitivity.

PMID- 10926315
TI  - Glucose metabolism of the thyroid in autonomous goiter measured by F-18-FDG-PE.
AB  - The radiolabeled glucose analogue F-18-Fluoro-Deoxyglucose (F-18-FDG) and
      Positron Emission Tomography (PET) were used to measure glucose metabolism of the
      thyroid in vivo. We evaluated patients with autonomous goitre before therapy with
      radioiodine in comparison to patients with normal thyroids. 30 patients with
      autonomous goitre underwent scanning the day before radioiodine therapy. 19
      patients with head or brain tumours and normal thyroids were the controls.
      Overall F-18-FDG uptake was determined for all thyroids and proved to be
      significantly higher in autonomy patients compared to controls and in
      disseminated autonomous goitre slightly but not significantly higher than in
      focal autonomy. In autonomy patients F-18-FDG uptake increased with increasing
      radioiodine uptake and shorter radioiodine half-life. These results indicate that
      glucose metabolism is enhanced in the thyroids of patients with focal and
      disseminated autonomy. The negative correlation of radioiodine half-life and
      glucose metabolism as well as the positive correlation of radioiodine uptake and
      glucose metabolism suggest connections of glucose metabolism and iodine-dependent
      hormone synthesis in thyroid cells.

PMID- 10926316
TI  - Continuous rise of urinary iodine excretion and drop in thyroid gland size among
      adolescents in Mecklenburg-West-Pomerania from 1993 to 1997.
AB  - Improved legislation (1989, 1993), as well as education of the public, are likely
      to improve the iodine supply for the German population. Children and adolescents
      will be the first to profit. We investigated thyroid size and urinary iodine
      excretion in a total of 2906 students aged 10 to 18 in Mecklenburg-West-Pomerania
      in 1993, 1995, and 1997. The median urinary iodine excretion rose from 73
      microg/g creatinine in 1993 to 133 microg/g in 1997. The prevalence of goiter,
      according to the reference range of Gutekunst, dropped from 33% to 10% over the
      same interval, and the median thyroid size declined from 11 ml to 6 ml. While
      only 6% of the test subjects excreted more than 150 microg iodine per g
      creatinine in 1993, this figure rose to 33% in 1997. The improved alimentary
      iodine supply is due to the increased use of iodine enriched salt by the food
      industry, food factories and in common food supply services.

PMID- 10926317
TI  - Interleukin-6 is inhibited by glucocorticoids and stimulates ACTH secretion and
      POMC expression in human corticotroph pituitary adenomas.
AB  - Interleukins and their receptors are expressed intrinsically in the anterior
      pituitary and regulate hormone production and cell proliferation. It has
      previously been shown that interleukin-6 (IL-6) regulates hormone secretion in
      normal pituitary cells and cell lines. Here we examined the effects of IL-6 on
      propiomelanocortin (POMC) expression and ACTH production in corticotroph adenoma
      cells in vitro. We found that IL-6 stimulates both ACTH secretion and POMC gene
      expression in corticotroph adenoma cell cultures. This first demonstration of the
      stimulatory action of IL-6 on human corticotroph adenoma cell function provides
      further evidence for a direct action of IL-6 on corticotroph pituitary cells. We
      have confirmed previous reports of IL-6 production by corticotroph adenoma cells
      and in addition, demonstrated for the first time that the synthetic
      glucocorticoid dexamethasone is a potent suppressor of intratumoral IL-6
      production. This intratumoral produced IL-6 may be in part responsible, in an
      autocrine manner, for the stimulation of ACTH synthesis and secretion. Our
      results suggest that IL-6 might play a role in the pathogenesis of Cushing's
      disease. However, elevated glucocorticoid levels in patients with Cushing's
      disease may prevent excessive action of IL-6 on ACTH production and tumor
      progression of corticotroph adenomas in vivo.

PMID- 10926318
TI  - Determinants of within-subject variation of fasting serum leptin concentrations
      in healthy subjects.
AB  - The hormone leptin is considered to contribute to body weight regulation through
      modulation of feeding behavior and energy expenditure. The aim of the present
      study was 1) to assess the day-to-day within-subject variation (biovariability)
      of serum leptin concentrations in healthy subjects and 2) to investigate whether
      this variation is associated with food intake, exercise, anthropometric
      measurements or various metabolic covariates (insulin, C-peptide and glucagon,
      glucose, lactate, 3-hydroxybutyrate (3-OHB), triglycerides, non-esterified-fatty
      acids and glycerol). Serum leptin levels were taken daily on 12 consecutive days
      after an overnight fast in 12 healthy subjects with a mean (SD) age of 22.7 (1.5)
      yr. and a BMI of 22.8 (1.6) kg/m2. Food intake, exercise, anthropometric
      measurements and various metabolic covariates were also determined during this
      period. The overall mean of serum leptin concentration was 33.3 pmol/L with a
      within-subject SD range of 27-41 pmol/L and a between-subject SD range of 18-61
      pmol/L. The within-subject variance of serum leptin as a proportion of total
      variance was 9.5%. Within-subject variation of serum leptin concentrations is
      small in relation to between-subject variation in healthy, normal weight
      subjects. This has implications for the power of interventional or prospective
      studies. In men, 6.7% of the variation in serum leptin concentration was
      associated with body weight measured on the same day (p= 0.037). In women,
      however, 66% of the variation was negatively associated with 3-OHB measured on
      both the same and the previous day (p=0.0003 and 0.002), and positively
      associated with triglyceride concentration measured on the previous day
      (p=0.0017) and insulin measured on the same day (p=0.0002). Within-subject
      associations in women could be due to phasic changes in unmeasured variables,
      possibly related to the menstrual cycle or might suggest that energy balance may
      exert a delayed influence on serum leptin levels, with plasma 3-OHB and
      triglycerides acting as markers for the state of the fat stores that regulate
      leptin secretion. The differences between the genders remain unexplained,
      however.

PMID- 10926319
TI  - Effect of four cGMP analogues with different mechanisms of action on hormone
      release by porcine ovarian granulosa cells in vitro.
AB  - The aim of our in-vitro experiments was to examine the role of cGMP-dependent
      intracellular mechanisms in control of ovarian hormone secretion, as well as to
      understand, whether cGMP effect on the ovary may be mediated by either protein
      kinase G (PKG), cGMP-gated ion channels (CGI) or cGMP-specific phosphodiesterases
      (PDE). We compared the effects of the cGMP analogues 8-pCPT-cGMP, an activator of
      PKG 1-alpha, 1-beta and type II and of CGI, but not of PDE: Rp-8-pCPT-cGMPS and
      Rp-8-Br-cGMPS, inhibitors of PKG, stimulators of CGI with no effect of PDE, and
      Rp-8-Br-PET-cGMPS, an inhibitor of both, PKG and CGI and stimulator of PDE (all
      at 0.01, 0.1, 1, 10 or 100 nM), on the release of oxytocin (OT) and progesterone
      (P) by cultured porcine granulosa cells. It was observed, that Rp-8-pCPT-cGMPS
      significantly (p<0.05) suppressed OT release when given at 1 or 10 nM. Rp-8-Br
      cGMPS increased OT output, when given at 1-10 nM too, but decreased it at 100 nM.
      Rp-8-Br-PET-cGMPS inhibited OT release at 1 nM. No influence of 8-pCPT-cGMP on OT
      output was found. 8-pCPT-cGMP stimulated P release at 0.1, 10 or 100 nM. All
      other cGMP analogues studied suppressed P release at all doses used. The present
      observations suggest the involvement of cGMP-dependent intracellular mechanisms
      in control of ovarian steroid and nonapeptide hormone release. The lack of
      association between patterns of influence of cGMP analogues on CGI and PDE, and
      the coincidence of the majority of effects of cGMP analogues on P, OT and PKG may
      indirectly indicate that cGMP action on release of ovarian hormones is mediated
      mainly by PKG, but not by CGI or PDE.

PMID- 10926320
TI  - Age-related differences in the effects of bacterial endotoxin (LPS) upon the
      release of LHRH, gonadotropins and hypothalamic inhibitory amino acid
      neurotransmitters measured in tissues explanted from intact male rats.
AB  - In adult rats, bacterial endotoxin (lipopolysaccharide or LPS) is known to
      diminish the activity of the reproductive axis, mainly by inhibiting luteinizing
      hormone-releasing hormone (LHRH) secretion; until now, this effect has not been
      studied in immature rats. The aim of the present study was to evaluate the effect
      of LPS 1) on LHRH output (and associated changes in the release of inhibitory
      amino acid neurotransmitters such as gamma-aminobutyric acid (GABA) and taurine)
      by superfused hypothalamic fragments, and 2) on gonadotropin secretion by
      incubated hemipituitaries, obtained from young adult (60-day-old) and
      peripubertal (30-day-old) intact male rats. In adult animals, LPS induced a
      significant inhibition (50% of basal values) of LHRH release, accompanied by an
      increase in GABA and taurine output. In juvenile rats the inhibition of LHRH
      secretion by LPS attained 90% of basal values (p<0.0001 versus adult rats), and
      the concurrent increase in GABA release was significantly greater (p<0.0001
      versus adult rats). LPS did not affect in vitro gonadotropin secretion in adult
      animals. Conversely, the release of these hormones was significantly (p<0.001 and
      <0.02 for LH and FSH, respectively) reduced in 30-day-old rats. Our results
      demonstrate the existence of age-related differences in the effect of LPS on LHRH
      and gonadotropin secretion. These differences might well be attributed to an
      increased activity of the hypothalamic GABAergic system. Furthermore, the
      participation of other factors known to play a role in immune-neuroendocrine
      relationships (e.g., corticotropin-releasing hormone, testosterone) is discussed.

PMID- 10926321
TI  - Changes in distribution of androgen receptor during maturation of rat ovarian
      follicles.
AB  - Sequential changes in androgen receptor (AR) distribution were investigated in
      rat ovarian follicles during their physiological development. Mature female
      Wistar rats, exhibiting a regular 4-day oestrous cycle, were killed in succession
      on the day of oestrus, metoestrus, dioestrus, and pro-oestrus. Excised ovaries
      were submitted to immunohistochemical procedure in which polyclonal androgen
      receptor antibody, avidin-biotin-peroxidase complex, and DAB were used. Strong AR
      immunostaining was located predominantly in the nuclei of the granulosa layer of
      preantral and very early antral follicles, present in the ovaries at all stages
      of the oestrous cycle. At early oestrus a decline in AR was noted in the mural
      granulosa cells of presumably recruited early antral follicles. The decline
      involved the area of appearing pseudostratification. During metoestrus and
      dioestrus AR decline proceeded towards the antrum, but the antral regions
      connected with COC by strings of granulosa cells or lying in close proximity to
      COC were always strongly AR-positive. It was only on the day of pro-oestrus that
      AR was confined to COCs and a few antral cells bordering the antrum. These
      findings indicate that during the oestrous cycle AR decline starts in the mural
      granulosa cells of oestrous antral follicles beginning to differentiate and is
      completed at pro-oestrus, but even before ovulation it does not extend to COC.
      The persistence of AR immunostaining in the latter region suggests that androgens
      can play here a paracrine role especially before ovulation. Atretic follicles
      showed a different pattern of AR distribution, dependent on their stage of
      development and the advancement of this process.

PMID- 10926322
TI  - Leucine 7 to proline 7 polymorphism in the neuropeptide y gene is associated with
      retinopathy in type 2 diabetes.
AB  - In this study we tested the hypothesis that the Leu7Pro7 polymorphism in prepro
      neuropeptide Y (NPY) gene could be a risk marker for the development of diabetic
      retinopathy and analyzed a well characterized cohort of patients with Type 2
      diabetes followed-up for 10 years from the time of diagnosis. The frequency of
      Leu7/Pro7-polymorphism was 9.3% (8 out of 86). At baseline, the frequency of
      retinopathy in patients with the Leu7/Pro7-polymorphism was 25% (2 out of 8) and
      in those without it 6.4% (5 out of 78) (p=0.126). At 10-year the respective
      figures were 88% and 50% (p=-0.040). The odds ratio for Leu7/Pro7-polymorphism in
      logistic regression analysis adjusted for age, gender and HbA1c was 8.97 (95%
      confidence intervals 1.09-98.0; p=0.049). Our finding based on elderly Finnish
      Type 2 diabetic subjects suggests that the Leu7Pro7-genotype in preproNPY gene is
      associated with the development of diabetic retinopathy.

PMID- 10926323
TI  - Decreased melatonin secretion in a phenotypically male 46,XX patient with classic
      21-hydroxylase deficiency.
AB  - The possible role of gonadal steroids and gonadotropins in regulating melatonin
      secretion has been suggested in clinical syndromes of the hypothalamic-pituitary
      gonadal axis. We describe the results of melatonin secretion in a 37-year old
      male patient who presented with azoospermia. The patient was an XX male, had
      classic simple virilizing form of 21-hydroxylase deficiency, which led to a
      masculine phenotype. He was ovariectomized at the age of three years and reared
      as a male. Melatonin production (aMT6s) was determined at baseline and during 12
      months of replacement therapy. Results were compared with those obtained in age
      matched male controls. Pretreatment aMT6s values were decreased (14.3 microg/24 h
      vs. 29.0+/-5.5 in controls). Dexamethasone replacement was associated with an
      increase in aMT6s values (19.3-20.9 microg/24 h). The addition of testosterone to
      dexamethasone replacement resulted in normalization of aMT6s (27.6-33.1 microg/24
      h) and serum 17OH progesterone, testosterone and estradiol levels. The present
      data indicate that androgen excess due to 21 hydroxylase deficiency is associated
      with decreased melatonin secretion. These results support the hypothesis that sex
      steroids modulate melatonin secretion.

PMID- 10926324
TI  - Immunohistochemical analysis of drug resistance-associated proteins in ovarian
      carcinomas.
AB  - Loss of function of the tumor suppressor gene p53, increased expression of
      glutathione-S-transferase pi (GST7pi) and the major vault protein are involved in
      drug resistance of ovarian carcinomas. However, a study comparing these factors
      has not yet been performed. Therefore, paraffin-embedded material of 213 ovarian
      tumors with well-documented follow-up was used for immunohistochemical analysis
      of p53 protein, GSTpi, and major vault protein (antibodies LRP-56, LMR-5). Forty
      six percent of the cases showed nuclear p53 accumulation. Strong immunoreactivity
      for GSTpi, LRP-56, and LMR-5 was seen in 50%, 36%, and 47%, respectively. p53
      positivity was most often found in serous carcinomas (p < 0.05). Strong GSTpi
      expression was the only factor that correlated with clinical resistance to
      chemotherapy (p = 0.04). In the whole group, as well as in FIGO III cases
      stratified for residual disease < or = and >2 cm, p53 and GSTpi correlated with
      an adverse outcome (p = 0.01 for p53 and p = 0.04 for GSTpi). Strong LRP-56 or
      LMR-5 staining was associated with a tendency towards poorer prognosis, without
      reaching statistical significance. In multivariate analysis for FIGO III, only
      residual disease and p53 proved to be independent prognostic factors. Our
      observations confirm the prognostic significance of p53 accumulation in ovarian
      carcinomas. Only GSTpi immunoreactivity was significantly correlated with drug
      resistance.

PMID- 10926325
TI  - Simultaneously occurring liver metastases of pheochromocytoma and medullary
      thyroid carcinoma--a diagnostic pitfall with clinical implications for patients
      with multiple endocrine neoplasia type 2a.
AB  - Malignant pheochromocytoma is an exceptional complication in patients with
      Multiple Endocrine Neoplasia Type 2a (MEN2a). In this paper, we report on a 53
      year-old male patient with an evident RET gene germline mutation, who
      simultaneously developed hepatic metastases of medullary thyroid carcinoma (MTC)
      and pheochromocytoma. Comprehensive immunohistochemical investigations were
      performed to elaborate markers which could be useful for differentiating between
      MTC metastases and pheochromocytoma, respectively. Calcitonin and CEA, in
      particular cytokeratins and trefoil factor family 1 (TFF1), were detectable
      exclusively in MTC, whereas all the other markers revealed a comparable
      expression in both MTC and pheochromocytoma. The only clues that could indicate a
      potential malignant course were size, a lack of sustentacular cells and hyaline
      globules, and a focal spindle cell pattern in pheochromocytoma. Owing to a wide
      agreement in cellular differentiation and a lack of specific, routinely
      applicable markers for pheochromocytomas, a comprehensive and goal-directed
      immunohistochemistry is required to rule out pheochromocytoma metastasis in
      patients with MEN2a. A misinterpretation could lead to harmful clinical
      complications, as shown in the present case.

PMID- 10926326
TI  - Correlation between histological grade, MIB-1, p53, and recurrence in 69
      completely resected primary intracranial meningiomas with a 6 year mean follow
      up.
AB  - Sixty-nine intracranial, totally excised meningiomas were immunostained for MIB-1
      and p53 protein expression. According to the 1993 WHO criteria, revised by Perry
      et al., the 69 meningiomas were classified into: grade I = 54 benign meningiomas,
      grade II = 10 atypical meningiomas, grade III = 5 malignant meningiomas. The
      patients were followed until death or for an average of 6.7 years. The 69
      meningiomas were divided into two groups, according to the absence (n = 42) or
      presence (n = 27) of recurrences. In the last group we included 3 patients who
      died of meningioma recurrence. According to the percentage of MIB-1 positively
      stained cells, meningiomas were divided into three groups: <1% (n = 36), 1-10% (n
      = 28), >10% (n = 5). We found the MIB-1 labeling index (LI) <1% in 33 grade I
      (61%) and in 3 grade II (30%) meningiomas. On the other hand, 7 grade II (70%)
      and all grade III (100%) meningiomas presented a MIB-1 LI >1%. Correlation
      between histological grade and MIB-1 LI was statistically significant (p =
      0.0006). The correlation between MIB-1 LI and follow-up was also highly
      significant (p < 0.001): the majority of meningiomas which did not recur (32/42
      equal to 76%) were characterized by a low (<1%) MIB-1 LI. In the recurrence group
      MIB-1 LI was significantly higher than in the disease-free patients' group.
      Moreover, MIB-1 appeared to be a prognostic parameter not strongly related to the
      histological grade. In fact, it was significantly higher in recurrent
      histologically benign meningiomas, as compared with benign meningiomas without
      recurrence (p = 0.0006). Positive p53 protein expression (>1%) was shown in 26/45
      meningiomas (57%), with an LI of 1-10% in 18 (40%) and an LI of >10% in 8 (17%)
      meningiomas. Although the p53 LI tended to be higher in atypical and malignant
      meningiomas, no significant correlation was found between the p53 expression and
      the recurrence (p = 0.05). The authors conclude that quantitative MIB-1 labeling
      is a useful technique in the routine diagnostic assessment of meningiomas, and
      helpful in obtaining more information about prognosis and thereby in planning the
      most suitable treatment.

PMID- 10926327
TI  - Clinical relevance of immunohistochemical expression of p53-targeted gene
      products mdm-2, p21 and bcl-2 in breast carcinoma.
AB  - The present study was designed to investigate the clinical/prognostic relevance
      of immunohistochemical expression of p53-targeted genes mdm-2, p21WAF1 and bcl-2
      alone and in combination with p53 for the indirect assessment of p53 gene status
      in breast cancer. 141 archival breast carcinomas were immunostained, and the
      putative mutational status of the p53 gene was defined in 21 of them, as a
      control for immunohistochemistry, using the polymerase chain reaction single
      strand conformational polymorphism (PCR-SSCP) analysis. Genetic changes of p53
      correlated significantly with p53 protein overexpression (p = 0.01) but did not
      do so with any of the related molecules. Immunohistochemical p53 status was
      directly correlated with mdm-2 (p = 0.0001), p21 (p = 0.0004) and inversely with
      bcl-2 (p = 0.005) expression. bcl-2 proved to be an independent marker of
      prognosis, p53 only in the group of node-positive carcinomas, whereas bcl-2-/p53+
      tumours revealed the worst prognosis. Mdm-2 and p21 expression was of prognostic
      significance neither alone nor in combination. We conclude that the detection of
      down-stream regulators of p53 does not increase the efficacy of
      immunohistochemistry in assessing the functional status of p53 in breast cancer;
      however, their combined analysis may help to select subgroups of patients at the
      extremes of risk for recurrence, or those with greater chances for survival.

PMID- 10926328
TI  - Merkel cell (neuroendocrine) carcinoma of the vulva. A case report with
      immunohistochemical and ultrastructural findings and review of the literature.
AB  - A new case of primary Merkel cell carcinoma (MCC) of the vulva is reported and
      the literature reviewed for noting its clinical presentation, microscopic,
      immunohistochemical and ultrastructural features, as well as for establishing the
      role of immunohistochemistry in the ultimate diagnosis of this uncommon and
      aggressive tumor. The lesion occurred in a 79 year old patient. Histologically,
      the tumor was composed of intradermal small cells with high mitotic index and
      frequent apoptosis. The immunohistochemical study showed positivity for wide
      spectrum and low molecular weight cytokeratins, epithelial membrane antigen,
      neurofilaments, neuron specific enolase and chromogranin A. Electron microscopy
      revealed intermediate filaments in a typical globular paranuclear arrangement.
      The coexpression of cytokeratins (including cytokeratin 20) and neurofilaments,
      both in typical globular paranuclear arrangement, made possible the diagnosis of
      MCC, differentiating it from other malignant small cell tumors such as
      neuroendocrine metastatic carcinoma.

PMID- 10926329
TI  - Carcinosarcoma of the parotid gland: cytological, clinicopathological and
      immunohistochemical study of a case.
AB  - Manifesting a putative origin from a pleomorphic adenoma, carcinosarcoma of the
      salivary gland is a heterologous neoplasm in which a sarcomatous and a
      carcinomatous component coexist. We present a parotid gland carcinosarcoma in a
      77-year-old man with peculiar morphological findings. Fine-needle aspiration
      cytology allowed a preoperative diagnosis of poorly differentiated carcinoma. At
      histologic examination, the tumor showed biphasic differentiation with an
      epithelial component made up of well-differentiated keratinizing squamous
      carcinoma and ductal-type adenocarcinoma, and a mesenchymal component, revealing
      focal areas of osteosarcoma and myoepithelial malignant proliferation.
      Carcinosarcoma is a very rare malignant neoplasm, accounting for 0.16% of
      malignant salivary gland tumors: only 60 cases have been reported, some of which
      arose "de novo", i.e., without clinico-pathologic evidence of a pre- or co
      existing pleomorphic adenoma.

PMID- 10926330
TI  - Primary alveolar soft part sarcoma of the stomach: a case report and review.
AB  - Alveolar soft part sarcoma (ASPS) is a rare tumor typically located in skeletal
      muscles and muscolofascial planes. Isolated cases of ASPS have been described as
      arising in the viscera. We report a mesenchymal tumor of the stomach in a 54-year
      old Italian woman without evidence of primary neoplasm elsewhere ten years
      following the initial diagnosis. The histologic, histochemical,
      immunohistochemical, and electron microscopic findings were all consistent with
      the diagnosis of ASPS and allowed differentiating it from morphologically similar
      and more common tumors, such as metastatic renal cell carcinoma and
      paraganglioma. The patient is alive and well ten years following the initial
      presentation.

PMID- 10926331
TI  - Calcifying fibrous pseudotumor involving the neck of a five-week-old infant.
      Presence of factor XIIIa in the lesional cells.
AB  - Calcifying fibrous pseudotumor is an uncommon lesion characterized by hyalinized
      collagen, psammomatous or dystrophic calcifications, and a predominantly
      lymphoplasmacytic infiltrate. Although the pathogenesis is unclear, a possible
      relationship with other inflammatory "pseudotumors" has been proposed. We
      describe the pathology of two right neck calcifying fibrous pseudotumors present
      in a five-week-old female infant. The masses had many of the pathologic features
      of calcifying fibrous pseudotumor. The presence of a florid, mixed infiltrate,
      and the occurrence of more than one lesion in the same patient, favor the
      proposal that calcifying fibrous pseudotumor may be a sclerosing end stage of
      inflammatory myofibroblastic tumor. However, the presence of a previously
      undescribed participation of Factor XIIIa-positive cells suggests that the tumor
      may be of dermal dendrocyte origin.

PMID- 10926332
TI  - Inhaled corticosteroids and the hypothalamic-pituitary-adrenal (HPA) axis: do we
      understand their interaction?

PMID- 10926333
TI  - A ten year review of colomycin.

PMID- 10926334
TI  - Measuring lung function in infancy.
AB  - Although the earliest reliable lung function tests in infants were performed as
      long as 40 years ago, there has only recently been a growth in this area, as
      simpler methods and better equipment and IT resources have been developed.
      Exciting information is accumulating about the normal physiology and pathology of
      the infant lung. Many basic questions are still unanswered and the ability to
      perform these tests remains confined to a few specialized centres. To co-ordinate
      the development of ILFT and establish standardization in a number of areas
      including measurement conditions, equipment specifications, methodology protocols
      and data analysis, international collaboration is necessary between the teams
      working in this field (Table 5). Collaborative groups are currently addressing
      these issues and are also developing recommendations regarding the design of
      randomized clinical trials, multi-centre studies and research agendas. Infant
      lung function testing remains primarily a research tool. Our aim should be not
      only to refine and develop the techniques of physiological measurement but to
      apply ILFT to the objective study of respiratory illness in infants in the
      clinical setting so as to aid in the prevention and treatment of these common,
      debilitating and costly diseases.

PMID- 10926335
TI  - Tuberculosis preventive therapy: perspective from a multi-ethnic community.
AB  - This study explores the knowledge, attitudes and perception of tuberculosis (TB)
      and how they affect adherence to preventive treatment. A qualitative study of 24
      subjects taking preventive therapy for TB was undertaken. Interviews were
      conducted in English using a structured questionnaire in a private room adjoining
      the outpatient clinic before the subject's appointment. The questionnaire
      included; (i) demographic details; (ii) background information on TB; (iii)
      knowledge and perception of TB and chemoprophylaxis. Data was analysed
      descriptively and thematically and subjected to statistical evaluation where
      appropriate. Outcome was assessed >6 months after the start of preventive
      treatment. The sample was representative of the ethnic mix of those attending the
      clinic. Knowledge of TB-was gained outside the family and covered transmission
      but few symptoms of active TB were recognized. The perceived threat from TB was
      high, although the estimated risk was low. Knowledge of preventive therapy
      exceeded the general knowledge of TB, although the latter was associated with
      better adherence. Most denied knowledge of the risk of hepatitis from isoniazid.
      Defaulters failed to attend their first appointment, attributed more side effects
      to isoniazid and perceived a longer waiting time in clinic. Adherence is better
      with a general knowledge of TB and attendance at the first appointment and could
      be improved by a single daily tablet, warnings about dizziness and discussion of
      the difficulties of taking a 6 month course of treatment.

PMID- 10926336
TI  - Erythromycin inhibits beta2-integrins (CD11b/CD18) expression, interleukin-8
      release and intracellular oxidative metabolism in neutrophils.
AB  - Macrolides have therapeutic benefits on chronic inflammatory airway diseases.
      Thus, macrolides are supposed to have variable biological effects apart from
      antimicrobial activity. Neutrophil adherence and influx with oxidants and
      cytokines production implicates involvement in airway inflammation. To
      investigate whether erythromycin (EM) affects neutrophil activity in vitro,
      lipopolysaccharide (LPS)-treated neutrophils were continuously incubated for 4 h
      in the absence or presence of increasing doses of EM from 1 microg ml(-1) to 100
      microg ml(-1) in the last 2 h. Leukocyte adhesion molecules Mac-1 and
      intracellular H2O2(DCFH) were determined by flowcytometric assay. IL-8 and
      TNFalpha in supernatant was measured by ELISA method. The expression of Mac-1 and
      mean intracellular DCF fluorescence intensity (DCFH) of neutrophils significantly
      increased after stimulation with LPS. Pretreatment with EM significantly
      decreased LPS induced Mac-1 expression on neutrophils compared with LPS
      stimulation only. EM alone (100 microg ml(-1)) also decreased Mac-1 expression on
      neutrophils. EM significantly reduced the LPS-increased DCFH. EM alone (100
      microg ml(-1)) also caused a decrease in DCFH. Increasing doses of EM also
      significantly decreased the IL-8 released by LPS-stimulated neutrophils. In
      conclusion, EM exerts a direct effect on the neutrophils by downregulating the
      expression of beta2-integrin on neutrophils, thus leading to a decrease in the
      intracellular H2O2, as well as the production of IL-8. Our conclusion provides an
      explanation for the clinical efficacy of erythromycin in neutrophil-mediated
      airway inflammation.

PMID- 10926337
TI  - Formoterol via Turbuhaler gave better protection than terbutaline against
      repeated exercise challenge for up to 12 hours in children and adolescents.
AB  - We aimed to compare the protective effect of single doses of 4.5 and 9 microg of
      formoterol fumarate (F), 0.5 mg terbutaline sulphate (T) and placebo (P), all via
      Turbuhaler, against exercise-induced bronchoconstriction (EIB) in children.
      Twenty-seven asthmatic children, showing a fall of > or =20% in FEV1 after a
      standardized exercise challenge test (ECT) combined with cold air (-10 degrees C)
      inhalation, were randomized in this cross-over, double-blind study. They had a
      mean age of 12.6 years (range 8-17 years), mean baseline FEV1 90% (73.9-105.6%)
      of predicted normal value. Seventeen children used inhaled glucocorticosteroids
      (120-750 microg day(-1)). ECTs were performed 15 min and 4, 8, and 12 h after
      drug administration. F significantly reduced the fall in FEV1 after ECT to 5.4%
      (15 min), 5.2% (4 h), 8.2% (8 h) and 9.3% (12 h) after 4.5 microg, and 2.5%,
      3.0%, 5.0% and 5.4% after 9 microg, compared with a fall of 18.4%, 15.7%, 15.6%
      and 16.5% in FEV1 after P. The fall after T was 3.3%, 11.6%, 14.4% and 19.1%
      after 15 min, 4, 8 and 12 h respectively. The difference between F and T was
      statistically significant from 4 h and onward (P-value for all comparisons <
      0.05). Children using a single dose of either formoterol Turbuhaler 4.5 or 9
      microg had significantly better bronchoprotection against repeated exercise
      challenge up to 12 h compared with placebo and from 4 h onward compared with
      terbutaline Turbuhaler 0.5 mg.

PMID- 10926338
TI  - Trends in bronchial hyperresponsiveness, respiratory symptoms and lung function
      among adults: West and East Germany. INGA Study Group. Indoor Factors and
      Genetics in Asthma.
AB  - Previous studies have shown higher prevalences of bronchial hyperresponsiveness
      (BHR), respiratory symptoms and atopic sensitization among adults in Western
      Germany than in Eastern Germany. One of the aims of the joint project INGA
      (INdoor Factors and Genetics in Asthma) is to assess incidence, prevalence and
      trends for asthma, BHR and atopic diseases over a time period of 11 years (1990
      2001) in the former West (Hamburg) and East Germany (Erfurt), with special
      reference to indoor exposure. INGA was designed as a case-control study following
      a cross-sectional study performed from 1990 to 1992 within the European Community
      Respiratory Health Survey (ECRHS). The database consisted of 1159 subjects in
      Hamburg and 731 subjects in Erfurt from the ECRHS (age 20-44). In 1995-1996, 107
      cases (diagnosed asthma, positive specific serum IgE, positive skin prick or
      PD20FEV1< or =2.0 mg methacholine at ECRHS) and 106 controls (none of the
      previous findings) participated in Hamburg (115 cases and 109 controls in
      Erfurt). The methodology was identical to the ECRHS and dose-response slopes
      (DRS) of the methacholine challenge were calculated as an index of
      responsiveness. In the control group, median values of DRS were 0.028% mg(-1)
      (1990-1992) and 0.044 (1995-1996) (P<0.01) in Erfurt. Corresponding values for
      Hamburg were 0.028 and 0.022 (NS). Corresponding values within the case groups
      were 0.041 and 0.049 (NS) for Erfurt, and 0.069 and 0.052 (P<0.05) for Hamburg.
      Thus, 4 years after the first survey, we found an increased BHR in the Erfurt
      control group while the bronchial responsiveness remained unchanged for the
      Hamburg group. These trends in BHR, which indicate the expected converging
      tendency between East and West Germany, have to be confirmed within the next INGA
      survey in 2000-2001.

PMID- 10926339
TI  - Comparison of high and low dose of the inhaled steroid, budesonide, as an initial
      treatment in newly detected asthma.
AB  - The importance of early initiation of inhaled steroids even in mild asthma has
      been documented in several studies. It is not, however, clear whether the
      treatment should be started with a high or a low dose of the inhaled steroid. We
      have compared the effects of high and low dose inhaled steroid, budesonide, in
      patients with newly detected asthma. We studied 101 adult patients with newly
      detected bronchial asthma who were without inhaled steroid or any regular
      pharmacological treatment for their asthma. The patients were randomly allocated
      to two treatment groups: one to receive 800 microg inhaled budesonide per day and
      the other to receive 200 microg inhaled budesonide per day. The drugs were given
      with a Turbuhaler dry powder inhaler. During the 3-month treatment period, no
      significant differences between the treatment groups were noted in morning or
      evening PEF values, in spirometric parameters, in asthmatic symptoms or in the
      use of rescue beta2-agonists. The decrease in bronchial hyperresponsiveness was,
      however, more marked in the high dose budesonide group, reaching a borderline
      significance (P=0.10 high vs. low dose budesonide). In addition, in serum markers
      of asthmatic inflammation significant differences were shown between the
      treatment groups. The decrease in the number of blood eosinophils during the
      treatment was more marked in the high dose budesonide group (P=0.02; high vs. low
      dose budesonide). In serum ECP no change was observed in the low dose budesonide
      group, but a marked decrease in the high-dose budesonide group (P=0.008; high vs.
      low dose budesonide). The change was even more marked with regard to serum EPX
      (P=0.005; high vs. low dose budesonide). Our results support the view that the
      treatment of newly detected asthma should be started with a high dose of inhaled
      steroid. The low dose may not be enough to suppress asthmatic inflammation
      despite good clinical primary response.

PMID- 10926341
TI  - Maximal inspiratory mouth pressures (PIMAX) in healthy subjects--what is the
      lower limit of normal?
AB  - BACKGROUND: Maximal inspiratory mouth pressures are suitable for non-invasive
      evaluation of respiratory muscle function. Different studies on PIMAX give
      predicted normal values and their relation to anthropometric data. Due to a large
      inter-subject variation of PIMAX, predicted values, however, maximal inspiratory
      mouth pressures are not suitable to define the individual expected normal PIMAX.
      What is the lower limit of the normal range? METHODS: PIMAX has been
      prospectively measured in a representative sample of 504 healthy volunteers (248
      males and 256 females) between 18 and 82 years of age with normal lung function.
      Age, height, weight, body mass index (BMI) and smoking status were recorded and
      incorporated stepwise in a multiple regression analysis to determine prediction
      equations. Lower limits of the normal range were defined as the fifth percentile
      of the residuals derived from the regression model. RESULTS: Mean values of PIMAX
      were 9.95 kPa for men and 7.43 kPa for women. Significant correlations were found
      with height, weight, BMI, FEV1, PEF and FVC (P<0.01). The strongest correlation
      appeared with sex and age (P<0.001). Smoking status and smoked pack-years were
      not independent predictors of inspiratory pressures. Lower limits of normal were
      59% for women and 60% for men of the predicted PIMAX. CONCLUSIONS: In the
      interpretation of maximal inspiratory mouth pressures, normal values should
      represent the lower limit of the normal range derived from the regression model
      in order to avoid false pathological results. Prediction equations as well as
      lower limits of normal resulting from a study cohort of healthy 18-82-year-olds
      are given and are recommended to be used by pulmonary function laboratories in
      young and old patients.

PMID- 10926340
TI  - A study to investigate the ability of subjects with chronic lung diseases to
      provide evidential breath samples using the Lion Intoxilyzer 6000 UK breath
      alcohol testing device.
AB  - The Lion Intoximeter 3000 has been used for evidential breath testing in the U.K.
      for some years. Some individuals with lung diseases have difficulty in providing
      evidential breath samples using the device. This study describes an investigation
      that we have carried out on a newer instrument--the Lion Intoxilyzer 6000UK-
      which is now in use in the U.K. The study was designed to investigate the ability
      of subjects with a variety of lung diseases to provide evidential breath samples
      using this device. The 40 adult subjects investigated comprized 10 normal
      controls, 10 with asthma, 10 with chronic obstructive pulmonary disease (COPD)
      and 10 with restrictive lung disease. After baseline spirometry, subjects were
      given alcohol to drink, the quantity based upon body weight. After a gap of at
      least 20 min, subjects were asked to provide evidential breath samples in
      accordance with.the test procedure built into the Lion Intoxilyzer 6000UK. The
      results showed that two asthmatic subjects, four with COPD and three with
      restrictive lung disease failed to provide evidential breath samples even after
      four attempts. Despite the device requiring a minimum sample volume of 1.2 l,
      eight of the nine subjects who failed had a forced vital capacity (FVC) of more
      than 1.5 l. Seven of these nine subjects had a forced expiratory volume in 1 sec
      (FEV1) of less than 1.0 l. In conclusion, this study has shown that some subjects
      with lung diseases may have difficulty in providing evidential breath samples
      using the Lion Intoxilyzer 6000 UK.

PMID- 10926342
TI  - Airway obstruction and chronic exertional dyspnoea in patients with persistent
      bronchial asthma.
AB  - In patients with COPD, flow limitation (FL) predicts chronic exertional dyspnoea
      (CED) better than routine spirometry. Whether, and to what extent, FL and CED are
      overlapping quantities in chronic asthma has not yet been defined. Forty
      consecutive clinically stable asthmatic patients without smoking history or
      cardiopulmonary disorders, were studied. In each subject respiratory function,
      including static and dynamic pulmonary volumes, was evaluated; maximal (MEFV) and
      partial (PEFV) expiratory V'-V curves and isovolumic partial to maximal flow
      ratio (M/P). FL was assessed in a seated patient by comparing tidal and PEFV
      curves; FL was detected when tidal flows were superimposed or exceeded those
      obtained during PEFV curves, and was expressed as a percentage of the expired
      control tidal volume (V(T)) affected by flow limitation (FL% VT). Dyspnoea was
      assessed by both MRC scale and Baseline Dyspnoea Index (BDI) focal score. Half of
      the patients were found to have FL. They were older, more dyspnoeic and more
      obstructed (P<0.03 - P<0.000005) than the non-FL group. FEV1, vital capacity
      (VC), age, body mass index, FL and M/P ratio were all related to dyspnoea scores.
      FL was significantly related to FEV1 (r = - 0.59). Multiple regression analysis
      showed that FEV1 (P=0.003, r2= 15-3% and P = 0.004, r2= 20.3%) and age (P =
      0.0006, r2 = 26.8% and P = 0.016, r2 = 11%) independently predicted a part of the
      variance of MRC (P = 0.0001, r2 = 42.1%) and BDI (P = 0.0008, r2 = 31.3%),
      respectively. With dyspnoea scale being the gold standard, diagnostic accuracy
      (sensitivity and specificity) by ROC (receiver operating characteristics)
      analysis was similar for FEV1 and FL. The results indicate that FL may be present
      in this subset of asthmatics. CED may not be easily explained by abnormalities of
      routine spirometry or FL, the largest part of the CED variance remained
      unexplained. Thus, routine spirometry, FL and CED in patients with bronchial
      asthma are only partially overlapping quantities which need to be assessed
      separately.

PMID- 10926344
TI  - Inhaled nebulized adrenaline improves lung function in infants with acute
      bronchiolitis.
AB  - Beta2-agonists have questionable symptomatic effect in infants with acute
      bronchiolitis, whereas inhaled, nebulized racemic adrenaline, commonly used in
      Norway, appears (clinically) to be effective. Limited lung function observations
      during acute bronchiolitis exists, and less for assessing possible effects
      inhaled adrenaline. In this preliminary study, tidal flow-volume loops were
      measured in 16 infants with acute bronchiolitis and seven healthy controls (mean
      age 7.9 and 4.4 months, respectively), with repeated measurements 15 min after
      inhaled nebulized racemic adrenaline (4 mg diluted in 2 ml saline) in nine
      bronchiolitis patients. The ratio of time to reach peak tidal expiratory flow to
      total expiratory time (tPTEF/tE) was significantly reduced in children with acute
      bronchiolitis (mean, 95% CI) (0.08, 0.05-0.10) compared to controls (0.31, 0.18
      0.43), with significant improvement after inhaled racemic adrenaline 0.19 (0.13
      0.25), parallel with significant clinical improvement. Lung function (tPTEF/tE)
      was reduced in infants with acute bronchiolitis and improved significantly after
      inhaled racemic adrenaline. Inhaled racemic adrenaline is potentially an
      important alternative for treating infants with acute bronchiolitis.

PMID- 10926343
TI  - Bronchiolitis obliterans-organizing pneumonia: an Italian experience.
AB  - The purpose of this study was to describe the clinical features at onset and
      outcome and the diagnostic approach in subjects with bronchiolitis obliterans
      organizing pneumonia (BOOP). Over a 7-year period we observed 78 cases of biopsy
      proven bronchiolitis obliterans-organizing pneumonia, in which well documented
      clinical and radiographic data were available. The final diagnosis of BOOP was
      validated when patients presented: (i) negative microbiological analysis on BAL
      fluid; (ii) a well documented improvement either spontaneous, or after steroid
      treatment or (iii) cases with progressive respiratory failure and increasing
      radiographic shadows, an open lung biopsy or autopsy that excluded other
      entities. There were 42 males and 36 females; the mean age was 61+/-12 years
      (range 12-85 years). Forty-two (54%) patients were current smokers, 25 (32%) had
      never smoked and 11 (14%) were ex-smokers. The clinical pattern at presentation
      of BOOP was more frequently similar to classical acute or sub-acute infectious
      pneumonia. Fever (63%), dyspnoea (58%) and dry cough (53%) were the typical
      symptoms on admission. A flu-like syndrome preceeding BOOP was observed in 21
      cases (27%). Inspiratory crackles (78%) were the most typical finding at physical
      examination. However, 13% of the patients were asymptomatic and an abnormal chest
      X-ray film was the reason for seeking medical attention. Radiographically the
      most frequent pattern of BOOP was a unilateral consolidation (44%) with lower
      field predominance. A migratory behaviour was present in 22% of the cases. High
      resolution computed tomographic (HR-CT) scan when performed, was more sensitive
      in detecting ground glass infiltrates, sub-pleural or peri-bronchovascular
      distribution or the presence of nodules or cavitation. Most patients (68%) were
      classified as having idiopathic BOOP. However, the same clinical-roentgenological
      pattern was observed in patients after radiotherapy for ductal breast carcinoma
      (6%), in collagen-vascular diseases (6%), related to drugs (9%), to infections
      serologically documented (4%), and to graft vs. host disease (4%). Four patients
      (all of whom had idiopathic BOOP) presented a rapid progressive respiratory
      failure needing mechanical ventilation. In another two cases respiratory failure
      appeared after a long period during which patients experienced exertional
      dyspnoea and low grade fever. BAL profile was characterized by lymphocytosis with
      a reduction of the CD4/CD8 ratio, associated with a slight increase of
      neutrophils and eosinophils and scattered mast cells. However in two cases we had
      an increased CD4/CD8 ratio and in one case the presence of a significant 12% of
      polyclonal B cells. In a few cases atypical (cytokeratin-positive cells)
      epithelial cells were detected: these cells were constantly present in the BAL
      fluid of patients with rapidly progressive respiratory failure. From the
      diagnostic point of view this series documents that transbronchial lung biopsy
      (coupled with BAL) can be the first diagnostic step. However, therapy can be
      started on the basis of BAL data (when a characteristic morphological and
      phenotypical profile is evident) in cases in which the clinical presentation is
      suggestive and a biopsy cannot be made. Most patients showed a rapid and good
      response to steroid therapy. However, three patients died (4%) in spite of
      steroid therapy (two cases) and steroid and cyclophosphamide therapy (one case).
      In conclusion, although clinical findings, chest X-ray film and CT Scan findings
      usually suggest the diagnosis a definite confirmation requires transbronchial
      lung biopsy and BAL and, less frequently, open lung biopsy.

PMID- 10926345
TI  - Salmeterol/fluticasone propionate combination therapy 50/250 microg twice daily
      is more effective than budesonide 800 microg twice daily in treating moderate to
      severe asthma.
AB  - Three hundred and fifty-three asthmatic patients who remained symptomatic despite
      treatment with budesonide 800-1200 microg day(-1) (or equivalent) were randomized
      to a new combination therapy comprising salmeterol 50 microg and fluticasone
      propionate 250 microg (Seretide, Advair, Viani 50/250 microg) twice daily or
      budesonide 800 microg twice daily for 24 weeks. Patients kept daily records of
      their morning and evening peak expiratory flow (PEF), daytime and night-time
      symptom scores and daytime and night-time use of rescue salbutamol. Mean morning
      PEF increased by 451 min(-1) (baseline 361 l min(-1)) in the
      salmeterol/fluticasone propionate combination (SFC) group and by 19 l min(-1)
      (baseline 358 l min(-1)) in the budesonide group over the 24 weeks. The adjusted
      mean morning PEF over weeks 1 to 24 was significantly greater in the SFC group,
      despite the > three-fold lower corticosteroid dose (406 vs. 380 l min(-1); P <
      0.001). A significantly greater improvement in evening PEF was also seen in the
      SFC group (adjusted mean 416 vs. 398 l min(-1); P<0.001). SFC also provided
      significantly better control of daytime symptoms and a significantly greater
      reduction in the requirement for rescue salbutamol compared with budesonide.
      These results demonstrate that SFC 50/250 microg twice daily is superior to
      budesonide 800 microg twice daily in the management of patients with moderate to
      severe asthma who are symptomatic on their existing dose of corticosteroid.

PMID- 10926346
TI  - Cost-effectiveness of salmeterol/fluticasone propionate combination product
      50/250 microg twice daily and budesonide 800 microg twice daily in the treatment
      of adults and adolescents with asthma. International Study Group.
AB  - Despite a good understanding of the disease and its treatments, asthma continues
      to place a large economic burden on healthcare systems. As such, it is important
      to consider the economic impact of alternative therapeutic options for the
      treatment of this condition to ensure that scarce resources are used in the most
      efficient manner possible. Thus, the aim of asthma management from an economic
      perspective is to reduce the burden of this disease through maximizing health
      gain with available resources. A prospective economic analysis was conducted as
      part of a multicentre, randomized, double-blind, comparative trial of
      salmeterol/fluticasone propionate combination product (SFC) 50/250 microg twice
      daily vs. budesonide (800 microg twice daily) in adults and adolescents with
      asthma who were symptomatic despite treatment with inhaled corticosteroids at
      doses of 800-1200 microg day(-1). Treatment effectiveness was measured in terms
      of successfully-treated weeks, defined as a > or =5% improvement in morning peak
      expiratory flow, episode-free days (a day without the need for rescue medication,
      no nocturnal awakening or adverse events) and symptom-free days. Cost
      effectiveness analyses were performed using direct healthcare and drug costs,
      from the perspective of the Swedish healthcare system (1998 prices), with
      appropriate sensitivity analyses to test the robustness of the findings. Overall,
      SFC produced significantly higher (P<0.001) proportions of successfully-treated
      weeks, episode-free days and symptom-free days. Direct asthma management costs
      were similar between the two groups [SEK19.6 ($US2.4) for SFC vs. SEK18.5
      (SUS2.2) for budesonide]. The cost per successfully-treated week was lower for
      SFC than for budesonide [SEK204 ($US24.8) vs. SEK300 ($US36.4) per week], as were
      the costs per episode-free day [SEK51.1 ($US6.2) vs. SEK75.1 ($US9.1) per day]
      and symptom-free day [SEK42.2 ($US5.1) vs. SEK53.0 ($US6.4) per day]. Incremental
      cost-effectiveness ratios showed that the additional costs to achieve additional
      benefits with SFC were minimal. Costs per additional successfully-treated week,
      symptom-free day and episode-free day with SFC were SEK31.6 ($US3.9), SEK9.2
      ($US1.1) and SEK7.7 ($US0.9), respectively, relative to budesonide. Sensitivity
      analysis showed that the results were stable over a wide range of assumptions.
      The results suggest that SFC is a more cost-effective treatment than budesonide
      in the management of moderate to severe asthma.

PMID- 10926347
TI  - Sustained release drug delivery to the lungs: an option for the future.
AB  - There are potential therapeutic advantages in administering drugs as sustained
      release formulations to the lungs. This presents the challenges of controlling
      drug release from particles within the lung environment while overcoming the
      natural clearance mechanisms. Approaches being adopted involve the administration
      of particles of small aerodynamic diameter to the alveoli and avoiding
      phagocytosis by high phospholipid content or large geometric particle size.
      Studies in animals have demonstrated the utility of such formulations.

PMID- 10926349
TI  - Clinical pharmacokinetics of goserelin.
AB  - Goserelin is a synthetic decapeptide analogue of luteinising hormone-releasing
      hormone (LHRH). For experimental purposes it has been administered subcutaneously
      as an aqueous solution, but for therapeutic use it is formulated as subcutaneous
      depots releasing goserelin over periods of 1 (3.6 mg) or 3 (10.8 mg) months.
      Pharmacokinetic data have been generated using a specific radioimmunoassay. When
      administered as a solution, goserelin is rapidly absorbed and eliminated from
      serum with a mean elimination half-life (t1/2beta) of 4.2 hours in males and 2.3
      hours in females. The shapes of the observed serum goserelin profiles following
      administration of the depots are primarily determined by the rate of goserelin
      release from the biodegradable lactide-glycolide copolymer matrix over periods of
      1 or 3 months. There is no clinically relevant accumulation of goserelin during
      multiple administration of these depots. Goserelin is extensively metabolised
      prior to excretion. Its pharmacokinetics are unaffected by hepatic impairment,
      but the mean t1/2beta increases to 12.1 hours in patients with severe renal
      impairment. This suggests that the total renal clearance (renal metabolism and
      unchanged drug) is decreased in patients with renal dysfunction. It is
      unnecessary to adjust the dose or administration interval when the depot
      formulations are administered to elderly patients or to those with impaired renal
      or hepatic function. Administration of a goserelin 3.6 mg or 10.8 mg depot
      results in an initial increase of luteinising hormone (LH) levels and in
      increases of serum testosterone or oestradiol levels in males and females,
      respectively. This is followed by a decrease in serum LH levels and suppression
      of testosterone or oestradiol to within the castrate or menopausal range,
      respectively. Subsequently, throughout treatment with goserelin depots, serum
      testosterone or oestradiol levels remain suppressed. Clinical outcomes following
      treatment of patients with prostate cancer, breast cancer and benign
      gynaecological conditions with goserelin are described briefly.

PMID- 10926351
TI  - Pharmacokinetics of quinupristin/ dalfopristin in patients with severe chronic
      renal insufficiency.
AB  - OBJECTIVE: To compare the pharmacokinetic profile of a single intravenous
      injection of quinupristin/dalfopristin, a new injectable streptogramin, in
      healthy young individuals and patients with severe chronic renal insufficiency. A
      secondary objective was to assess the relative tolerability of this dose in these
      patients compared with healthy individuals. PATIENTS AND PARTICIPANTS: 13
      patients with severe chronic renal insufficiency (creatinine clearance 6 to 28
      ml/min/1.73m2) were individually matched for gender, bodyweight and age to a
      healthy volunteer. METHODS: Participants received a single dose of
      quinupristin/dalfopristin 7.5 mg/kg bodyweight as a continuous 1-hour intravenous
      infusion, followed by serial blood sampling. RESULTS: The disposition profile of
      unchanged quinupristin was similar in the 2 groups. However, the elimination of
      quinupristin derivatives in patients with renal impairment tended to be
      decreased: mean peak plasma drug concentration (Cmax) and area under the
      concentration-time curve from zero to infinity (AUCinfinity) of quinupristin plus
      its active derivatives were about 1.4 times higher in the patients with renal
      impairment compared with healthy volunteers. The mean Cmax and AUCinfinity of
      both unchanged dalfopristin and dalfopristin plus its active derivatives were
      about 1.3 times higher in renally impaired patients than in healthy volunteers.
      Adverse events were generally mild and transient. No severe or serious adverse
      events were reported and no participants prematurely discontinued the study.
      Venous tolerability tended to be better in healthy volunteers than in the
      patients with renal impairment. CONCLUSION: These results suggest that no formal
      reduction in the dosage of quinupristin/dalfopristin is necessary in patients
      with severe chronic renal impairment.

PMID- 10926348
TI  - Clinical pharmacokinetics of nucleoside analogues: focus on haematological
      malignancies.
AB  - This review establishes the pharmacokinetic characteristics of the major
      nucleoside analogues with cytotoxic activity. Cytarabine, pentostatin,
      fludarabine, cladribine and gemcitabine are all prodrugs whose plasma
      pharmacokinetics do not fully reflect their therapeutic activity; after cellular
      uptake, these compounds undergo phosphorylation by deoxycytidine kinase before
      their incorporation into DNA results in cell death. Cytarabine is principally
      active in the S phase of the cell cycle and is most toxic to replicating cells,
      whereas pentostatin, fludarabine and cladribine are incorporated into DNA during
      the process in which strand breaks are repaired and are therefore cytotoxic to
      slowly replicating cells (although the action of pentostatin results from its
      inhibition of adenosine deaminase). Gemcitabine is unusual in being highly
      metabolised in solid tumour cells. The cytotoxic activity of pentostatin,
      fludarabine and cladribine against the clonal cells of lymphoproliferative
      disorders is accompanied by damage to normal lymphoid cells, which results in
      significant and long-lasting immunosuppression. Useful interactions between
      nucleoside analogues have been defined. Cells that are primed by exposure to
      fludarabine or cladribine exhibit enhanced accumulation of cytarabine
      triphosphate (the cytotoxic nucleotide of cytarabine) and an improved therapeutic
      effect against acute myeloid leukaemia and chronic lymphocytic leukaemia can be
      achieved by clinical schedules that exploit this effect. Combinations of
      alkylating agents and fludarabine or cladribine are also synergistic in producing
      significantly enhanced activity against refractory lymphoid malignancies, but at
      the cost of increased haematological toxicity. Developments in the clinical
      administration of gemcitabine are concentrating on efforts to extend the duration
      of exposure to the drug as a means of counteracting its rapid catabolism in the
      circulation. Future developments with this group of agents will further explore
      the use of fludarabine-based combination therapies to produce a transient period
      of myelosuppression and immunosuppression that is sufficient to permit the
      engraftment of allogeneic haemopoietic stem cells and also exploit the
      immunological benefits of graft-versus-tumour reactions. In addition, the
      clinical spectrum of activity of gemcitabine is also being extended by combining
      the drug with other active chemotherapeutic agents, such as cisplatin, and by
      early studies of its role as a radiosensitiser.

PMID- 10926352
TI  - Remifentanil in the horse: identification and detection of its major urinary
      metabolite.
AB  - Remifentanil (4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1
      piperidinepropionic acid methyl ester) is a mu-opioid receptor agonist with
      considerable abuse potential in racing horses. The identification of its major
      equine urinary metabolite, 4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1
      piperidinepropionic+ ++ acid, an ester hydrolysis product of remifentanil is
      reported. Administration of remifentanil HCl (5 mg, intravenous) produced clear
      cut locomotor responses, establishing the clinical efficacy of this dose. ELISA
      analysis of postadministration urine samples readily detected fentanyl
      equivalents in these samples. Mass spectrometric analysis, using solid-phase
      extraction and trimethylsilyl (TMS) derivatization, showed the urine samples
      contained parent remifentanil in low concentrations, peaking at 1 h. More
      significantly, a major peak was identified as representing 4-methoxycarbonyl-4
      [(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid, arising from ester
      hydrolysis of remifentanil. This metabolite reached its maximal urinary
      concentrations at 1 h and was present at up to 10-fold greater concentrations
      than parent remifentanil. Base hydrolysis of remifentanil yielded a carboxylic
      acid with the same mass spectral characteristics as those of the equine
      metabolite. In summary, these data indicate that remifentanil administration
      results in the appearance of readily detectable amounts of 4-methoxycarbonyl-4
      [(1-oxopropyl)phenylamino]-1-piperidinepropionic+ ++ acid in urine. On this
      basis, screening and confirmation tests for this equine urinary metabolite should
      be optimized for forensic control of remifentanil.

PMID- 10926353
TI  - Determination of lidocaine in hair of drug fatalities by headspace solid-phase
      microextraction.
AB  - The local anesthetic lidocaine was determined in hair by hydrolysis of the
      samples with 4% NaOH in the presence of excessive Na2SO4 and subsequent headspace
      solid-phase microextraction with a 65-microm Carbowax/divinylbenzene fiber, and
      gas chromatography-mass spectrometry measurement with etidocaine as the internal
      standard. The calibration curve was linear between 0.1 and 1000 ng/mg. The
      detection and quantitation limits were 0.1 and 0.4 ng/mg, respectively. The
      method was applied to hair samples of 49 drug fatalities, and positive results
      were obtained in 32 cases with lidocaine concentrations between 0.4 and 400 ng/mg
      and 675 ng/mg in one extreme case. For comparison, morphine, 6-acetylmorphine,
      codeine, dihydrocodeine, methadone, cocaine, and benzoylecgonine were also
      determined by usual methods. From segmental investigations in four of the cases
      and from comparison with the hair concentrations of the other drugs, it follows
      that lidocaine was consumed for a longer period of time as an adulterant of
      cocaine and heroin preparations.

PMID- 10926354
TI  - An assay evaluation of the methylene blue method for the detection of anionic
      surfactants in urine.
AB  - Adding detergent to urine intended for drug testing is one of many ways to
      adulterate the specimen. This modified methylene blue procedure allows the
      detection and quantitation of anionic surfactants in urine. One-hundred urine
      specimens that exhibited normal foaming when shaken gave anionic surfactant
      values lower than 36 microg/mL with a mean of 8.73 microg/mL. Most of the
      suspected adulterated specimens and spiked samples with only 100 microL of
      detergent in 60 mL of urine had values greater than 750 microg/mL. Based on the
      analysis of negative samples, a urine specimen with an anionic surfactant level
      of 100 microg/mL or greater could be considered adulterated and most likely will
      have levels greater than 800 microg/mL.

PMID- 10926355
TI  - Determination of methyl mercury in whole blood by ethylation-GC-CVAFS after
      alkaline digestion-solvent extraction.
AB  - A method for the determination of methyl mercury in whole blood samples based on
      ethylation-gas chromatography-cold vapor atomic fluorescence spectrometry after
      alkaline digestion-solvent extraction is described. The extraction procedure and
      conditions were optimized, and the matrix interference after extraction was
      critically investigated. The storage stability of MeHg in blood samples and a
      series of extracts was determined. The method detection limit was found to be
      approximately 0.02 ng/g for a 0.5-g blood sample with relative standard
      deviations of less than 10%. The accuracy and precision were evaluated by
      summarizing the quality-control (QC) data generated over a one and one half year
      period. Appropriate procedures for sample collection, transportation, and storage
      were adapted to the method. Using this method accompanied by explicit QC
      protocols and procedures, background levels of MeHg and total mercury in blood
      for 150 8-10-year-old Portuguese children with nonoccupational and nonamalgamal
      exposure were determined and reported with summarized QC data.

PMID- 10926356
TI  - Comparison of serum and salivary cotinine measurements by a sensitive high
      performance liquid chromatography-tandem mass spectrometry method as an indicator
      of exposure to tobacco smoke among smokers and nonsmokers.
AB  - Exposure to tobacco smoke, both from active smoking and from passive exposure to
      environmental tobacco smoke, can be monitored by measuring cotinine, a metabolite
      of nicotine, in a variety of biological sources including blood, urine, and
      saliva. Previously, a sensitive atmospheric-pressure ionization, tandem mass
      spectrometric (LC-API-MS-MS) method for cotinine measurements in serum was
      developed in support of a large, recurrent national epidemiologic investigation.
      The current study examined the application of this LC-API-MS-MS method to both
      serum and saliva cotinine measurements in a group of 200 healthy adults,
      including both smokers and nonsmokers. The primary objective of this study was to
      evaluate the relationship between serum and saliva cotinine concentrations to
      facilitate the linking of results from epidemiologic studies using salivary
      cotinine measurements to existing national data based on serum cotinine analyses.
      The results indicate that a simple, linear relationship can be developed to
      describe serum and saliva cotinine concentrations in an individual, and the
      expression describing this relationship can be used to estimate with reasonable
      accuracy (approximately +/- 10%) the serum cotinine concentration in an
      individual given his or her salivary cotinine result. It was further confirmed
      that saliva cotinine samples are generally quite stable during storage after
      collection, even at ambient temperatures, and this sample matrix appears to be
      well-suited to the requirements of many epidemiologic investigations.

PMID- 10926357
TI  - Screening procedure for detection of antidepressants of the selective serotonin
      reuptake inhibitor type and their metabolites in urine as part of a modified
      systematic toxicological analysis procedure using gas chromatography-mass
      spectrometry.
AB  - A gas chromatographic-mass spectrometric (GC-MS) screening procedure was
      developed for detection of selective serotonin reuptake inhibitors (SSRIs) in
      urine as part of a systematic toxicological analysis procedure. After acid
      hydrolysis of one aliquot of urine, another aliquot was added. The mixture was
      then liquid-liquid extracted at pH 8-9, acetylated, and GC separated. Using mass
      chromatography with the ions m/z 58, 72, 86, 173, 176, 234, 238, and 290, the
      possible presence of SSRIs and/or their metabolites could be indicated. The
      identity of positive signals in such mass chromatograms was confirmed by
      comparison of the peaks underlying full mass spectra with the reference spectra
      recorded during this study. The overall recoveries of citalopram, sertraline, and
      paroxetine ranged between 60 and 80%, and those of fluoxetine and fluvoxamine,
      which were destroyed during acid hydrolysis, were between 40 and 45%. The
      coefficients of variation were less than 10-20%, and the limit of detection was
      at least 100 ng/mL (signal-to-noise ratio = 3). This method allowed the detection
      of therapeutic concentrations of citalopram, fluoxetine, fluvoxamine, paroxetine,
      and sertraline in human urine samples.

PMID- 10926358
TI  - Distribution of Aconitum alkaloids in body fluids and tissues in a suicidal case
      of aconite ingestion.
AB  - A case involving a suicidal ingestion of Aconitum tubers is presented. A 40-year
      old woman in Hokkaido, Japan ingested ground aconite and died of aconite
      intoxication about 4 h after ingestion. The Aconitum alkaloids were quantitated
      using gas chromatography-selected ion monitoring from extracts of the body fluids
      and organs. The blood and urine concentrations of jesaconitine, the main alkaloid
      of the aconite in this case, were 69.1 ng/mL and 237.8 ng/mL, respectively.
      Higher values of the alkaloid were demonstrated in the kidneys, the liver, and in
      the bile rather than other organs or serum, suggesting the alkaloids were
      eliminated by the liver and kidneys. In the gastrointestinal tract, the highest
      value of jesaconitine (471.3 ng/g) was in the ileal contents. These findings show
      that Aconitum alkaloids were found in the liver and kidneys in much higher
      concentrations than in serum and suggest that they were eliminated not only via
      urine but also in feces. Feces may be useful to detect Aconitum alkaloid if other
      biological samples are not available.

PMID- 10926350
TI  - Drug interactions with cisapride: clinical implications.
AB  - Cisapride, a prokinetic agent, has been used for the treatment of a number of
      gastrointestinal disorders, particularly gastro-oesophageal reflux disease in
      adults and children. Since 1993, 341 cases of ventricular arrhythmias, including
      80 deaths, have been reported to the US Food and Drug Administration. Marketing
      of the drug has now been discontinued in the US; however, it is still available
      under a limited-access protocol. Knowledge of the risk factors for cisapride
      associated arrhythmias will be essential for its continued use in those patients
      who meet the eligibility criteria. This review summarises the published
      literature on the pharmacokinetic and pharmacodynamic interactions of cisapride
      with concomitantly administered drugs, providing clinicians with practical
      recommendations for avoiding these potentially fatal events. Pharmacokinetic
      interactions with cisapride involve inhibition of cytochrome P450 (CYP) 3A4, the
      primary mode of elimination of cisapride, thereby increasing plasma
      concentrations of the drug. The macrolide antibacterials clarithromycin,
      erythromycin and troleandomycin are inhibitors of CYP3A4 and should not be used
      in conjunction with cisapride. Azithromycin is an alternative. Similarly, azole
      antifungal agents such as fluconazole, itraconazole and ketoconazole are CYP3A4
      inhibitors and their concomitant use with cisapride should be avoided. Of the
      antidepressants nefazodone and fluvoxamine should be avoided with cisapride. Data
      with fluoxetine is controversial, we favour the avoidance of its use. Citalopram,
      paroxetine and sertraline are alternatives. The HIV protease inhibitors
      amprenavir, indinavir, nelfinavir, ritonavir and saquinavir inhibit CYP3A4.
      Clinical experience with cisapride is lacking but avoidance with all protease
      inhibitors is recommended, although saquinavir is thought to have clinically
      insignificant effects on CYP3A4. Delavirdine is also a CYP3A4 inhibitor and
      should be avoided with cisapride. We also recommend avoiding coadministration of
      cisapride with amiodarone, cimetidine (alternatives are famotidine, nizatidine,
      ranitidine or one of the proton pump inhibitors), diltiazem and verapamil (the
      dihydropyridine calcium antagonists are alternatives), grapefruit juice,
      isoniazid, metronidazole, quinine, quinupristin/dalfopristin and zileuton
      (montelukast is an alternative). Pharmacodynamic interactions with cisapride
      involve drugs that have the potential to have additive effects on the QT
      interval. We do not recommend use of cisapride with class Ia and III
      antiarrhythmic drugs or with adenosine, bepridil, cyclobenzaprine, droperidol,
      haloperidol, nifedipine (immediate release), phenothiazine antipsychotics,
      tricyclic and tetracyclic antidepressants or vasopressin. Vigilance is advised if
      anthracyclines, cotrimoxazole (trimethoprim-sulfamethoxazole), enflurane,
      halothane, isoflurane, pentamidine or probucol are used with cisapride. In
      addition, uncorrected electrolyte disturbances induced by diuretics may increase
      the risk of torsade de pointes. Patients receiving cisapride should be promptly
      treated for electrolyte disturbances.

PMID- 10926359
TI  - Discrimination of dimethylamphetamine and methamphetamine use: simultaneous
      determination of dimethylamphetamine-N-oxide and other metabolites in urine by
      high-performance liquid chromatography-electrospray ionization mass spectrometry.
AB  - A simple and sensitive method by high-performance liquid chromatography
      electrospray ionization mass spectrometry (LC-ESI-MS) has been investigated for
      the simultaneous determination of dimethylamphetamine (DMA), its specific yet
      labile main metabolite dimethylamphetamine-N-oxide (DMAO), and other metabolites,
      methamphetamine (MA) and amphetamine (AP), in urine. A combination of Bond Elut
      SCX columns for the solid-phase extraction of urine and a semi-micro SCX column
      for LC separations provided satisfactory results. The use of acetonitrile/5mM
      ammonium acetate buffer adjusted to pH 4 (65:35, v/v) as the mobile phase at a
      flow rate of 0.2 mL/min was found to be the most effective. The detection limits
      were 5 ng/mL for DMAO, 10 ng/mL for DMA and MA, and 50 ng/mL for AP in the SIM
      mode.

PMID- 10926360
TI  - Enhanced selectivity in the determination of delta9-tetrahydrocannabinol and two
      major metabolites in serum using ion-trap GC-MS-MS.
AB  - Cannabinoids were extracted from serum with C18 SPE cartridges and analyzed as
      their trimethylsilyl (TMS) derivatives. A benchtop gas chromatography-tandem mass
      spectrometry (GC-MS-MS) system based on an ion trap with external ionization was
      used. Quantitation was done in relation to trideuterated internal standards in
      dual MS-MS mode. Confirmation of the identity for the three compounds of
      interest, delta9-tetrahydrocannabinol (THC), 11-hydroxy-delta9
      tetrahydrocannabinol (11-OH-THC), and 11-nor-9-carboxy-delta9
      tetrahydrocannabinol (THCCOOH), was achieved by registering the daughter spectra
      in full scan mode. It was possible to identify the three compounds at
      concentrations down to 0.25 microg/L for THC, 0.5 microg/L for 11-OH-THC, and <
      2.5 microg/L for THCCOOH by comparison with reference spectra. The limits of
      quantitation are better than 2 microg/L for THC, 5 microg/L for 11-OH-THC, and 8
      microg/L for THCCOOH. The within-run and day-to-day precision for the three
      analytes were very similar and ranged from 4.2 to 10.4%.

PMID- 10926361
TI  - Rapid multimethod for verification and determination of toxic pesticides in whole
      blood by means of capillary GC-MS.
AB  - A rapid and single multimethod was developed to determine substances of different
      pesticide classes in whole blood in the event of acute human intoxications, as
      required by EU Commission Directive 96/46. The method was validated by an in
      house and an independent laboratory validation. Whole blood is hemolyzed and then
      deproteinized. After extraction of the supernatant, blood levels are determined
      by gas chromatography-mass spectrometry. The method, which can be performed
      within 120 min, covers 15 active substances (8 organophosphate pesticides, 2
      carbamates, 3 pyrethroids, 1 azole, and 1 organochlorine pesticide) classified as
      toxic or very toxic. These compounds can be identified down to concentrations
      between 100 and 1000 ng/mL by comparison of their mass spectra to those in a
      commercial pesticide mass spectra library. Using the standard addition method,
      they can be quantitated down to concentrations between 30 and 200 ng/mL. These
      limits of quantitation are considered to be sufficient in comparison to
      respective LD50 values.

PMID- 10926362
TI  - Rapid analysis of halothane in biological samples using headspace solid-phase
      microextraction and gas chromatography-mass spectrometry--a case of a double
      homicide.
AB  - A simple, rapid, and sensitive method for the analysis of halothane in biological
      samples was developed. The procedure describes the extraction of halothane from
      blood, liver, kidney, brain, urine, bile, and stomach contents by headspace solid
      phase microextraction (HS-SPME) followed by capillary gas chromatography coupled
      with mass spectrometry (GC-MS). The recovery in blood samples after addition of
      ammonium sulfate and sulfuric acid was 72% compared to a sample prepared in water
      (100%). Linearity was established over a concentration range of 0.1-100 mg/kg of
      spiked blood samples with an excellent coefficient of correlation (0.996) and a
      limit of detection of 0.004 mg/kg. The time for analysis was approximately 40 min
      per sample including the extraction step. The procedure was used for quantitation
      of halothane in various samples in a case of a double homicide. HS-SPME in
      combination with GC-MS was an effective method for the determination and
      quantitation of halothane in biological material.

PMID- 10926363
TI  - Attempted suicide by ingestion of methoxychlor.
AB  - A rare case involving an attempt to commit suicide by ingestion of a commercially
      available product containing methoxychlor as the active ingredient is presented.
      Clinical symptoms exhibited by the patient included no response to stimuli, pale
      skin, and profuse sweating. A serum sample collected at the time of admission to
      the hospital was found to contain 0.67 microg/mL of methoxychlor. The
      determination of methoxychlor was performed using gas chromatography-mass
      spectrometry.

PMID- 10926364
TI  - Ephedrine abuse for doping purposes as demonstrated by hair analysis.

PMID- 10926365
TI  - Elevated GHB in citrate-buffered blood.

PMID- 10926366
TI  - Structural and functional characterization of insulin receptor substrate proteins
      and the molecular mechanisms of their interaction with insulin superfamily
      tyrosine kinase receptors and effector proteins.
AB  - The literature data on the role of IRS1/IRS2 proteins, endogenous substrates for
      insulin receptor tyrosine kinase, in transduction of signals generated by insulin
      superfamily peptides (insulin, insulin-like growth factor) were analyzed. The
      molecular mechanisms of the functional coupling of IRS proteins with peptide
      receptors possessing a tyrosine kinase activity and SH2 domain-containing
      proteins (phosphatidylinositol 3-kinase, Grb2 adaptor protein, protein
      phosphotyrosine phosphatase) were discussed. The structural and functional
      properties of IRS proteins (distribution of functional domains and sites for
      tyrosine phosphorylation; conservatism of amino acid sequences) were
      characterized. The data on the alternative pathways of transduction of signals
      which are generated by insulin and related peptides and do not involve IRS
      proteins were analyzed. These pathways are realized through Shc proteins or via
      direct interaction between receptors and SH2 proteins. Amino acid sequences of
      IRS proteins and insulin superfamily tyrosine kinase receptors were compared. The
      homologous regions in IRS proteins and receptors, which can be responsible for
      their coupling with phosphatidylinositol 3-kinase and protein phosphotyrosine
      phosphatases, were identified.

PMID- 10926367
TI  - On the influence of pigment-protein interactions on energy transfer processes in
      photosynthetic membrane structures. 3. The FMO complex of Chlorobium tepidum at
      high pressure.
AB  - The low-temperature absorption spectra of the Chlorobium tepidum FMO
      bacteriochlorophyll-protein complex at various pressures have been calculated
      within the framework of mini-exciton theory. The dependences of the Qy transition
      energies of the monomeric pigments on pressure have been found by means of
      functional minimization. This functional includes the parameters of both
      theoretical and experimental absorption spectra at low temperatures and various
      pressures. The dependences obtained are compared with those derived for the
      exciton transition energies, which have been obtained by deconvoluting absorption
      spectra with seven Gaussian components at each pressure. The pressure increase
      has been shown to result in the increased coupling energy between both the
      pigment molecules themselves and pigments and amino acid residues. The pigment
      molecules capable of binding histidines and water molecules have been shown to
      have the greatest and smallest responses to increased pressure, respectively. The
      couplings of Bchl molecules with the surrounding amino acid residues have been
      shown to change both the exciton delocalization index and the exciton
      distribution between the pigment molecules within the protein subunit; the
      increased pressure does not change these parameters significantly.

PMID- 10926368
TI  - Reduction of the Ca2+ transport systems in mouse young brown fat cells.
AB  - Principal differences in the kinetics and amplitude of Ca2+ response to
      norepinephrine were found between freshly isolated young differentiated brown fat
      cells. An increase in the Ca2+ concentration in the cytoplasm ([Ca2+]i) in the
      young cells was unusually slow (A[Ca2+]i = 0.03 nM/s) in comparison with that in
      the differentiated cells, and the Ca2+ influx from the outside was not induced by
      Ca2+ mobilization agents, such as thapsigargin and ionomycin. Ionomycin increased
      [Ca2+]i up to 150 nM in a Ca2+-free medium and up to 270 nM in the normal medium.
      This results in that the intracellular Ca2+ stores in freshly isolated young
      cells are rather poor, and the mechanism of capacitive calcium entry does not
      virtually function. The data on chemical modification of Ca2+ channels in the
      plasma membrane by thimerosal suggest that the conductance of these channels is
      low and/or their number in young brown fat cells is insignificant.

PMID- 10926369
TI  - Relationship between formate hydrogen lyase and proton-potassium pump under
      heterolactic fermentation in Escherichia coli: functional multienzyme
      associations in the cell membrane.
AB  - Anaerobically grown glucose-fermenting E. coli cells produce molecular hydrogen,
      acidify the medium and uptake potassium ions. It was shown that the H2 release
      and the proton-potassium exchange with the fixed (2H+/K+) stoichiometry of the
      initial DCC-sensitive fluxes were lost in mutants with the deleted fdhF gene or
      the hycA-H operon responsible for the biosynthesis of formate dehydrogenase H
      (FDH,H) or hydrogenase 3 (H3), respectively, which are the main components of the
      formate hydrogen lyase FHL(H). However, both processes occurred in mutants with
      the deleted hycE, hycF or hycG genes encoding the major and minor components of
      H3, respectively. The K+ uptake was sensitive to the osmotic shock resulting from
      glucose addition to the medium and decreased significantly in the presence of
      valinomycin. The H2 release and the 2H+/K+ exchange were absent in the mutant
      with the deleted hycB gene encoding the corresponding minor component of H3. This
      mutant acidified the medium and uptook K+ with Km typical for TrkA, but the
      stoichiometry of the DCC-inhibited fluxes was variable, and the K+ gradient
      between the cytoplasm and the medium in this mutant was lower than in the mutants
      lacking other minor components of H3. The results obtained suggest that the hycB
      gene product, FdhF and HycE, form probably the FHL(H) complex that directly
      interacts with the H+-ATPase complex F0F1 and the TrkA(H) system of K+ uptake.
      Such a multienzyme association is responsible for the H2 production and 2H+/K+
      exchange. The major and other minor components of H3 have probably no direct role
      in the H2 production and 2H+/K+ exchange. H2 production by precursor's or hycE
      mutant's protoplasts treated with toluene was shown to occur upon addition of the
      thiol reagent dithiothreitol to the medium containing ATP, potassium ions, NAD+,
      and NADH. H2 production was inhibited by DCC. The quantity of available thiol
      groups in membrane vesicles of the precursor or the hycE, hycF or hycG mutants,
      in which the H2 production and 2H+/K+ exchange were observed, was larger than in
      other mutants. The number of SH groups decreased in the presence of DCC. These
      results indicate a significance of the thiol groups for the function of the
      proposed association.

PMID- 10926370
TI  - Effects of fluoride and vanadate on K+ transport across the erythrocyte membrane
      of Rana temporaria.
AB  - K-Cl cotransport activity in frog erythrocytes was estimated as a Cl- -dependent
      component of K+ efflux from cells incubated in Cl- - or NO3- -containing medium
      at 20 degrees C. Decreasing the osmolality of the medium resulted in an increase
      in K+ efflux from the cells in a Cl- medium but not in an NO3- medium. Treatment
      of red cells with 5 mM NaF caused a significant decrease (approximately 50%) in
      K+ loss from the cells in iso- and hypotonic Cl- media but only a small decrease
      in K+ loss in isotonic NO3- medium. Addition of 1 mM vanadate to an isotonic Cl-
      medium also led to a significant reduction in K+ efflux. Similar inhibitory
      effects of NaF and vanadate on K+ efflux in a Cl- medium, but not in an NO3-
      medium were observed when the incubation temperature was decreased from 20 to 5
      degrees C. Thus, under various experimental conditions, NaF and vanadate
      inhibited about 50% of Cl- -dependent K+ efflux from frog red cells probably due
      to inhibition of protein phosphatases. Cl- -dependent K+ (86Rb) influx into frog
      erythrocytes was nearly completely blocked (approximately 94%) by 5 mM NaF. In a
      NO3- medium, K+ influx was mainly mediated by the Na+,K+ pump and was unchanged
      in the presence of 5 mM NaF, 0.03 mM Al3+ or their combination. These data
      indicate that G proteins or cAMP are not involved in the regulation of Na+,K+
      pump activity which is activated by catecholamines and phosphodiesterase blockers
      in these cells.

PMID- 10926371
TI  - Hypochlorous acid and human blood low density lipoproteins modified by
      hypochlorous acid increase erythrocyte adhesion to endothelial cells.
AB  - The ability of hypochlorous acid (HOCl) (anion form - hypochlorite, OCl-) and
      HOCl/OCl- -modified human blood low density lipoproteins (HOCl-LDLs) to stimulate
      erythrocyte adhesion to endothelial cell monolayers was studied. LDLs were
      modified by incubating at different HOCl/OC- concentrations. This led to a damage
      of proteins and lipids. We found (1) a more than 20-fold decrease of LDL
      fluorescence intensity (extinction at 285 nm, emission at 340 nm), (2)
      accumulation of secondary (TBA-reactive substances) and final (Schiff bases)
      products of lipid peroxidation, and (3) increase in the electrophoretic mobility
      of LDLs. Preincubation of endothelial cells (ECs) with HOCI/OCl- (up to 50
      microM) enhanced erythrocyte adhesion to the EC monolayer. Preincubation of ECs
      with HOCl-LDLs (up to 250 microM of HOCI//OCl- during LDL modification) (1)
      caused an increase in the cholesterol/phospholipid molar ratio in EC and (2)
      enhanced adhesion of erythrocytes to endothelium. Application of HOCl/OCl- at
      concentrations above 50 microM or treatment of LDLs with 500 microM HOCl resulted
      in the cytotoxic effect on ECs and led to a decrease in the molar
      cholesterol/phospholipid ratio in ECs and adhesion of erythrocytes to
      endothelium. The results suggest that HOCl/OCl- at physiological concentrations
      stimulates the adhesion of blood cells to the endothelium and cholesterol
      accumulation in the vessel wall ECs either directly or due to LDL modification.
      Both effects could be important in the development of many vascular diseases.

PMID- 10926372
TI  - Estimation of surface area in very low density human serum lipoproteins.
AB  - The surface area of very low density lipoproteins (VLDL) from the serum of 15
      healthy donors and the surface area of artificial lipid particles have been
      estimated. The artificial particles were prepared as a mixture of egg
      phosphatidylcholine and triolein. Two fluorescent probes - energy donor and
      acceptor - were placed on the surface, and Forster's nonradiative energy transfer
      was measured; the transfer efficiency is a function of surface area. The
      fluorescent probe K-68 (4-[5-(phenyloxazolyl-2)-1-pentadecyl)pyridinium) was used
      as a donor, and DSP-12 (dimethylamino)styryl-N-dodecylpyridinium) was used as an
      acceptor. The specific surface area of the artificial lipid particles was
      estimated to be 0.585 +/- 0.015 nm2 per phosphatidylcholine molecule, which is
      15% less than in lipid bilayers. The specific area of VLDL particles was 259 +/-
      65 m2 per g of total VLDL. This value is close to the specific area of low
      density lipoproteins (LDL), and corresponds to the area of a spherical particle
      10-12 nm in radius. However, VLDL are assumed to be much larger particles as
      compared with LDL. Therefore, the new data of the VLDL surface area raise a
      problem of revision of the existing VLDL models.

PMID- 10926373
TI  - The role of reactive oxygen species in membrane potential changes in macrophages
      and astrocytes.
AB  - Involvement of reactive oxygen species (ROS) in changes of the plasma membrane
      potential of mouse peritoneal macrophages and astrocytes (U118 cell line) under
      the action of different agents has been studied. Membrane potential was measured
      using the voltage-dependent fluorescent oxonol dye DiBAC4(3). Agonists which
      stimulate macrophages to release ROS (the fMLP peptide and platelet activating
      factor) caused prolonged hyperpolarization. Experiments with the fluorescent
      probe 2',7'-dichlorofluorescein diacetate have shown that astrocytes release ROS
      upon the action of C5a complement anaphylatoxin (but not C3a). The effect of C5a
      was accompanied with hyperpolarization of the astrocyte plasma membrane.
      Treatment of the cells with agents which do not induce ROS generation (C3a,
      lipopolysaccharide, interferon-gamma) depolarized the plasma membrane.
      Hyperpolarization of both cell types was significantly decreased in the presence
      of superoxide dismutase (but not catalase). Moreover, the O2- -generating system
      caused a marked hyperpolarization of both cell types. The data obtained suggest
      that O2- is involved in the macrophage and astrocyte hyperpolarization response.

PMID- 10926374
TI  - Hemagglutinin-induced fusion of HAb2 and PLC cells: dynamics of fusion pore
      conductance.
AB  - Infection of cells with influenza virus is mediated by the virus envelope protein
      hemagglutinin (HA) which induces fusion of viral and target membranes. Earlier we
      showed using fluorescent microscopy that HAb2 cells expressing HA on their plasma
      membranes fused with PLC cells when pH of the external medium was decreased to 
      5. In the present work we used double whole-cell recording to monitor the
      intercellular conductance in HAb2/PLC cell pairs during fusion. In approximately
      40% of cell pairs the pH drop induced the intercellular conductance, which we
      interpret as the formation of a fusion pore. The following stages of the
      conductance growth were distinguished: initial fluctuations near zero (flicker),
      a subsequent slow increase up to 1-4 nS and a final rapid increase up to 10-100
      nS (complete fusion). The first detectable intercellular conductance change
      (opening of a fusion pore) was accompanied by an increase in the conductances of
      both HAb2 and PLC cell membrane. This observation suggests that the early pore
      complex should be leaky. The dynamics of the intercellular conductance appeared
      to depend upon the voltage difference between the fusing HAb2 and PLC cells:
      voltages higher than 40 mV facilitated the conductance growth.

PMID- 10926375
TI  - Stalk dynamics and lipid flow upon membrane hemifusion.
AB  - A hydrodynamic theory describing the stalk dynamics and lipid flows upon BLM
      hemifusion was developed. The value of intermonolayer viscosity, etar, for
      membranes formed from azolectin mixed with lysophosphatidylcholine (7.10(-4)
      mg/ml) in n-decane, etar approximately 10(-9) g/s, was determined from comparison
      of the theoretical calculations and literature data. For membranes formed in
      squalene, the values etar approximately 10(-7) g/s for phosphatidylethanolamine
      and etar approximately 2-10(-7) g/s for azolectin were obtained. The calculated
      values are close to the published results of independent experiments which shows
      that the developed theory describes well the stalk growth and lipid flow.

PMID- 10926376
TI  - Bronchodilation in mechanically ventilated patients: how much is enough and how
      best to deliver?

PMID- 10926377
TI  - Bronchodilator therapy with metered-dose inhaler and spacer versus nebulizer in
      mechanically ventilated patients: comparison of magnitude and duration of
      response.
AB  - OBJECTIVE: Four-hour comparison of the bronchodilator response of albuterol
      administered via metered-dose inhaler (MDI) with spacer versus small-volume
      nebulizer (SVN) to mechanically ventilated patients with chronic obstructive
      pulmonary disease (COPD). DESIGN: Prospective randomized clinical trial. SETTING:
      Medical intensive care unit in a university hospital. PATIENTS: Thirteen
      mechanically ventilated COPD patients. INTERVENTION: Albuterol administration of
      4 puffs (0.4 mg) or 10 puffs (1.0 mg) via MDI with spacer or 2.5 mg via SVN to
      mechanically ventilated patients in order to assess the bronchodilator response
      over 4 hours. MEASUREMENTS AND RESULTS: Mechanically ventilated patients were
      enrolled in a randomized crossover study wherein one group received 4 puffs (0.4
      mg) or 2.5 mg of albuterol and another group received 10 puffs (1.0 mg) or 2.5 mg
      of albuterol on separate days. Respiratory mechanics measurements were obtained
      over 4 hours. Total airway resistance declined by 14.4 +/- 3.8% after 4 MDI
      puffs, 18.3 +/- 1.8% after 10 MDI puffs, or 13.7 +/- 2.6% after 2.5 mg via SVN,
      compared to baseline (p < 0.01). After albuterol delivery, airway resistance
      remained improved for 90-120 minutes (p < 0.05) and returned to baseline by 4
      hours with all treatments. CONCLUSION: The airway response to albuterol
      administration via MDI and SVN to mechanically ventilated patients was similar in
      magnitude and duration, returning to baseline by 240 minutes. In stable,
      mechanically ventilated COPD patients, albuterol may be administered via MDI with
      spacer or via SVN every 4 hours.

PMID- 10926378
TI  - New horizons in respiratory care: the pharmacology of inhaled aerosol drug
      therapy.

PMID- 10926379
TI  - The fate of inhaled drugs: the pharmacokinetics and pharmacodynamics of drugs
      administered by aerosol.
AB  - Prior to a drug achieving its effects (ie, pharmacodynamics), there are numerous
      events within the body that determine its ultimate fate. The effects of the "body
      on the drug" has been referred to as pharmacokinetics-how the favorable lung-to
      systemic effects predicted from this exercise translate into practice. Inhaled
      drugs have enjoyed the major feature of having "local" effects on the target
      organ of the lung. Broadly, lower doses can be used and adverse effects are often
      less than with oral or parenteral administration. Nevertheless, key features of
      respiratory drugs and their administration can impact their fate and ultimate
      utility. This review has provided some relevant examples of basic
      pharmacokinetics principles as related to inhaled products, with emphasis on
      those factors that help to partition lung-to-systemic effects.

PMID- 10926380
TI  - Inhalable drugs for systemic therapy.
AB  - Although oral and injectable drug formulations still dominate the market,
      interest in pulmonary delivery has been rising steadily. Given patients' desire
      for an alternative to injections, and recent advances in aerosol science and
      pulmonary medicine, the potential for improved disease management outcomes by
      using aerosols for systemic drug delivery should lead the way for a shift to
      inhalables.

PMID- 10926381
TI  - Inhaled antimicrobial therapy: from cystic fibrosis to the flu.
AB  - Recent controlled clinical trials have confirmed the usefulness of aerosolized
      tobramycin in cystic fibrosis and have emphasized the importance of ensuring
      adequate lung delivery of inhaled antimicrobials. For purulent tracheobronchitis
      associated with prolonged mechanical ventilation it has recently been established
      that it is possible to deliver substantial and measurable doses of medications to
      the airway via aerosolization, but controlled studies are needed to determine the
      efficacy and safety of inhaled antibiotic therapy in this setting. However,
      prophylactic aerosolized antibiotic therapy in an intensive care unit setting may
      be counterproductive. Aerosolized pentamidine continues to provide prophylaxis
      against PCP in a substantial minority of subjects with human immunodeficiency
      virus infection who are intolerant of oral agents. The effectiveness of
      aerosolized amphotericin B as prophylaxis against aspergillosis in neutropenic
      patients needs to be evaluated in a large clinical trial. Zanamivir, an inhibitor
      of neuraminidase, delivered via inhalation, shows promise in the treatment of
      uncomplicated influenza infection, but more data are needed on its effectiveness
      and safety in patients with preexisting respiratory disease. The development of
      new chemical entities, more efficient delivery systems, and more precise
      measurement of dose-response and regional pulmonary drug distribution of inhaled
      antimicrobials suggest that this somewhat neglected topic in therapeutics may be
      about to receive an increased degree of attention.

PMID- 10926382
TI  - Comparing inhaled corticosteroids.
AB  - There are currently available 5 different inhaled corticosteroids, in a variety
      of different inhalation delivery devices. In the near future there will certainly
      be more inhaled corticosteroids in newer inhalation delivery devices available in
      the United States. Tremendous amounts of information will be made available about
      the relative advantages and disadvantages of these new products. Most of this
      information will relate to measures of potency, pharmacokinetic profiles, and
      technical issues about the ease of use. The respiratory care practitioner should
      be aware that estimating the clinical benefits from the topical anti-inflammatory
      effects of these newer products will be difficult to determine from this
      information. Also difficult to understand will be the effects of easier to use
      inhalation delivery devices on patient adherence to prescribed inhaled
      corticosteroid dosing regimens. Information from well designed clinical trials
      should be the basis for comparing presently available and newly developed inhaled
      corticosteroids.

PMID- 10926383
TI  - Inhaled adrenergic bronchodilators: historical development and clinical
      application.
AB  - The adrenergic bronchodilators that have been developed for oral inhalation
      represent successive refinement in terms of receptor specificity and duration of
      action. Beta agonist bronchodilators have durations of 4-6 hours, or, in the case
      of salmeterol, of up to 12 hours, offering convenient dosing. Inhalation of the
      aerosol formulations targets the lung directly. The release of levalbuterol now
      provides an agent with a single isomer active on beta-2 receptors. The currently
      available agents offer clinicians and patients with reversible obstructive lung
      disease a choice of sophisticated drugs for airway smooth muscle relaxation.
      Although improvements in the drugs have reduced adverse effects and beta agonists
      are considered safe, concerns persist about the effect of beta agonists in
      asthma. An improved understanding of asthma pathophysiology may lead to more
      appropriate use of beta agonists in asthma.

PMID- 10926384
TI  - Clinical aspects of inhaled anticholinergic therapy.
AB  - Anticholinergic therapy is directed toward muscarinic receptors within the lung.
      Inhaled quaternary muscarinic antagonists are used because they cause less
      systemic adverse effects than other types of antimuscarinic drugs. Of the 5
      possible muscarinic receptors, the lung contains three: M1, M2, and M3.
      Antagonism of the M1 and M3 receptors results in bronchodilation, primarily in
      the larger airways. The efficacy of the antimuscarinic bronchodilators cannot be
      entirely explained by this mechanism, and there is probably peripheral activity
      as well. The use of inhaled antimuscarinic drugs is well tolerated, and the
      efficacy is maintained with chronic use. Although ipratropium is the first-line
      therapy for symptomatic COPD, it and other similar drugs can also be used to
      treat other obstructive diseases. Ipratropium is available in an MDI, in solution
      for small-volume nebulizer, and in combination with albuterol in an MDI. Newer
      antimuscarinic agents are being developed that are more selective for the M1 and
      M3 sites and last longer. Research is continuing to better understand the sites
      of action of these agents as well as to develop even more effective drugs.

PMID- 10926385
TI  - Evaluating the efficacy of mucoactive aerosol therapy.
AB  - The aerosol route is attractive for the delivery of mucoactive medications.
      Mucoactive medications include mucolytics, which depolymerize polymers of mucin
      (classic mucolytics) or DNA/actin (peptide mucolytics), mucokinetic agents, which
      increase cough clearance, mucoregulatory medications, which decrease abnormal
      mucus secretion, and expectorants and ion channel modifiers. Despite the
      widespread use of these medications, there are few well conducted studies and
      thus few data clearly supporting (or failing to support) their use. This will
      change as our understanding of mucociliary physiology and pharmacology increases
      and as well designed and well powered clinical trials are conducted with
      appropriate outcome measurements. Effective mucoactive therapy should make a
      profound impact on the care of patients with chronic bronchitis, asthma, cystic
      fibrosis, and inflammatory airways disease, and will be essential for the
      effective delivery of gene therapy vectors and bioactive peptides to the airway
      epithelium.

PMID- 10926386
TI  - Aerosol device selection: evidence to practice.
AB  - Therapeutic aerosols are generated by pneumatic jet nebulizers, ultrasonic
      nebulizers, pressurized metered-dose inhalers, and dry powder inhalers. Some of
      the drug preparations used in these devices are formulated to work with specific
      devices. Although design improvements in aerosol devices have led to improved
      lung deposition, decreased oropharyngeal deposition, decreased waste of drug,
      greater ease of use, and lower environmental impact, optimizing the use of
      aerosol devices requires patient and caregiver instruction, in combination with
      proper device use and maintenance. Optimizing aerosol delivery requires knowledge
      of a number of technical details, and caregivers should stay abreast of the
      continuing advancement of technologies and techniques associated with aerosol
      delivery, especially in light of emerging devices and formulations.

PMID- 10926387
TI  - Evidence of nosocomial Stenotrophomonas maltophilia cross-infection in a
      neonatology unit analyzed by three molecular typing methods.

PMID- 10926388
TI  - Hospital characteristics associated with colonization of water systems by
      Legionella and risk of nosocomial legionnaires' disease: a cohort study of 15
      hospitals.

PMID- 10926389
TI  - Respiratory syncytial virus in a general hospital and the need for extensive
      measures.

PMID- 10926390
TI  - Selecting protective apparel for the degree of exposure anticipated.

PMID- 10926391
TI  - Using electronic media to conduct an emergency infection control committee vote.

PMID- 10926392
TI  - Using alcohol for hand antisepsis: dispelling old myths.

PMID- 10926393
TI  - Skin irritation and dryness associated with two hand-hygiene regimens: soap-and
      water hand washing versus hand antisepsis with an alcoholic hand gel.
AB  - OBJECTIVE: To compare the frequency of skin irritation and dryness associated
      with using an alcoholic-hand-gel regimen for hand antisepsis versus using soap
      and water for hand washing. DESIGN: Prospective randomized trial with crossover
      design. Irritation and dryness of nurses' hands were evaluated by self-assessment
      and by visual assessment by a study nurse. Epidermal water content of the dorsal
      surface of nurses' hands was estimated by measuring electrical capacitance of the
      skin. SETTING: Miriam Hospital, a 200-bed university-affiliated teaching
      hospital. PARTICIPANTS: Thirty-two nurses working on three hospital wards
      participated in the trial, which lasted 6 weeks. RESULTS: Self-assessment scores
      of skin irritation and dryness decreased slightly during the 2 weeks when nurses
      used the alcoholic-hand-gel regimen (mean baseline score, 2.72; mean final score,
      2.0; P=.08) but increased substantially during the 2 weeks when nurses used soap
      and water (mean baseline score, 2.0; mean final score, 4.8; P<.0001). Visual
      assessment scores by the study nurse of skin irritation and dryness did not
      change significantly when the alcoholic-hand-gel regimen was used (mean baseline
      and final scores were both 0.55), but scores increased substantially when nurses
      used soap and water (baseline score, 0.59; mean final score, 1.21; P=.05).
      Epidermal water content of the dorsal surface of nurses' hands changed little
      when the alcoholic-hand-gel regimen was used (mean+/-standard deviation baseline
      electrical capacitance reading, 24.8+/-6.8; mean final reading, 25.7+/-7.3), but
      decreased significantly (skin became dryer) with soap-and-water hand washing
      (mean baseline, 25.9+/-7.5; mean final reading, 20.5+/-5.4; P=.0003).
      CONCLUSIONS: Hand antisepsis with an alcoholic-hand-gel regimen was well
      tolerated and did not result in skin irritation and dryness of nurses' hands. In
      contrast, skin irritation and dryness increased significantly when nurses washed
      their hands with the unmedicated soap product available in the hospital. Newer
      alcoholic hand gels that are tolerated better than soap may be more acceptable to
      staff and may lead to improved hand-hygiene practices.

PMID- 10926394
TI  - An outbreak of influenza A in a neonatal intensive care unit.
AB  - OBJECTIVES: Investigation of an outbreak of influenza A in a neonatal intensive
      care unit (NICU) with examination of risk factors for infection and outcomes.
      DESIGN: Retrospective cohort study of infants admitted to the unit during the
      outbreak period. Prospective survey of NICU staff and mothers of infants in the
      cohort study. SETTING: Level III nursery in a university-affiliated tertiary
      referral center. RESULTS: Nineteen infants in the NICU were infected with
      influenza A There were six symptomatic cases and one death who had evidence of
      virus-associated hemophagocytic syndrome at autopsy. Amantadine prophylaxis was
      offered to the NICU staff, and amantadine therapy was given to five of the six
      symptomatic infants. Mechanical ventilation, gestational age, birth weight,
      Clinical Risk Index for Babies score, and twin pregnancy were associated with
      acquisition of influenza A on univariate analysis. Mechanical ventilation (odds
      ratio [OR], 6.2; P=.02) and twin pregnancy (OR, 7.0; P=.04) remained as
      significant risk factors for infection on multiple logistic regression analysis.
      Only 15% of respondents to the NICU staff survey were vaccinated against
      influenza. There was no association between a history of an influenza-like
      illness during pregnancy and acquisition of influenza A by infants of mothers who
      responded to the maternal survey (OR, 0.91; P=1.0). CONCLUSIONS: Influenza A is
      an important pathogen in the neonatal population and is readily transmissible in
      the NICU setting.

PMID- 10926395
TI  - Association of antibiotic utilization measures and control of multiple-drug
      resistance in Klebsiella pneumoniae.
AB  - OBJECTIVE: To study the association of antibiotic-utilization measures and
      control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two
      hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae
      at two hospitals were compared before and after acute interventions, including
      emphasis on Contact Precautions and education in antibiotic utilization.
      Antipseudomonal beta-lactam antibiotic use was measured before and after the
      interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell
      DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination
      was the major mechanism of emergence at hospital A; emergence was polyclonal at
      hospital B. Antibiotic-utilization interventions at both institutions included
      physician education regarding the association of ceftazidime use and MDR K.
      pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the
      preintervention period, to 1,248 g in the postintervention period. Piperacillin
      tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K.
      pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates
      (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77
      (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from
      6,533 g in the preintervention period to 4,792 g in the postintervention period.
      Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime
      resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of
      383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%)
      of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed
      continued decrease in piperacillin-tazobactam resistance despite increased use at
      both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly
      important for control of MDR K. pneumoniae, whether emergence is clonal or
      polyclonal.

PMID- 10926396
TI  - The epidemiology of mupirocin resistance among methicillin-resistant
      Staphylococcus aureus at a Veterans' Affairs hospital.
AB  - OBJECTIVE: To describe the clinical and molecular epidemiology of mupirocin
      resistant (MR) and mupirocin-susceptible (MS) methicillin-resistant
      Staphylococcus aureus (MRSA) at a Veterans' Affairs hospital and to assess risk
      factors associated with the acquisition of MR MRSA. DESIGN: All clinical MRSA
      isolates for the period October 1990 through March 1995 underwent susceptibility
      testing to mupirocin. Mupirocin resistance trends were measured, and MS MRSA and
      MR MRSA isolates underwent typing by pulsed-field gel electrophoresis (PFGE). A
      retrospective case-control study was conducted to evaluate risk factors for
      having MR versus MS MRSA. SETTING: The James H. Quillen Veterans' Affairs Medical
      Center in Mountain Home, Tennessee, included a 324-bed acute-care hospital, a 120
      bed nursing home, and a 525-bed domiciliary. Colonizations and infections with
      MRSA were endemic, and mupirocin ointment was commonly used. PATIENTS: Inpatients
      and outpatients at the facility. RESULTS: MS MRSA was recovered from 506 patients
      and MR MRSA from 126. Among MR MRSA isolates, 58% showed low-level mupirocin
      resistance (minimum inhibitory concentration [MIC] > or = 4 to 256 microg/mL),
      and 42% showed high-level mupirocin resistance (MIC > or = 512 microg/mL). A
      significant increase (P=.002) in the number of high-level MR isolates occurred
      during the 1993 to 1995 period. A case-control study showed that presence of a
      decubitus ulcer correlated with high-level resistant isolates (P<.05). The
      distribution of PFGE patterns did not differ for MR and MS MRSA CONCLUSIONS: Use
      of mupirocin ointment in a program aimed at managing endemic MRSA infection or
      colonization resulted in a significant increase in the recovery of high-level MR
      MRSA isolates. These isolates appeared to emerge from our existing MRSA pool. A
      case-control study provided few clues concerning patients likely to harbor MR
      MRSA. We confirmed the position that the extended use of mupirocin ointment
      should be avoided in settings where MRSA is endemic.

PMID- 10926398
TI  - A pseudo-outbreak of Aureobasidium species lower respiratory tract infections
      caused by reuse of single-use stopcocks during bronchoscopy.
AB  - OBJECTIVE: To investigate and control an apparent outbreak of lower respiratory
      tract infections due to Aureobasidium species. DESIGN: Outbreak investigation.
      SETTING: University-affiliated medical center. PATIENTS: Nine patients who
      underwent bronchoscopy between June and August 1998. RESULTS: Ten bronchoalveolar
      lavage (BAL) fluid cultures from nine patients grew Aureobasidium species during
      the outbreak period; whereas, respiratory specimens from only two patients grew
      Aureobasidium species during the preceding 6 years. No patient was judged to have
      true infection due to Aureobasidium species either before or after bronchoscopy.
      Nine of the 10 bronchoscopies that yielded Aureobasidium species were performed
      in the outpatient bronchoscopy suite. The Aureobasidium isolates were not
      associated with any one bronchoscope. Observation of bronchoscopy procedure
      revealed that plastic stopcocks labeled for single use were reused on different
      patients during BAL. There was no record of how many times each stopcock was
      being reused. After each use, the stopcocks were placed in an automated
      disinfection machine designed for bronchoscopes. Culture of the stopcocks after
      they had been "disinfected" yielded a heavy growth of Aureobasidium species,
      while culture of fluid from the automated disinfection machine was negative.
      Reuse of the stopcocks was halted, and, during the following 6-month period,
      Aureobasidium species were not isolated from any BAL specimen. CONCLUSIONS: Reuse
      of medical equipment labeled for single use is potentially hazardous, especially
      if no quality control system is in place to monitor sterility and function after
      reprocessing.

PMID- 10926397
TI  - A heterogeneous outbreak of Enterobacter cloacae and Serratia marcescens
      infections in a surgical intensive care unit.
AB  - OBJECTIVE: To investigate an outbreak of invasive disease due to Enterobacter
      cloacae and Serratia marcescens in a surgical intensive care unit (ICU). DESIGN:
      Pulsed-field gel electrophoresis (PFGE) analysis of restriction fragments was
      used to characterize the outbreak isolate genotypes. A retrospective cohort study
      of surgical ICU patients was conducted to identify risk factors associated with
      invasive disease. Unit staffing data were analyzed to compare staffing levels
      during the outbreak to those prior to and following the outbreak. SETTING: An
      urban hospital in San Francisco, California. PATIENTS: During the outbreak
      period, December 1997 through January 1998, there were 52 patients with a minimum
      ICU stay of > or = 72 hours. Of these, 10 patients fit our case definition of
      recovery of E. cloacae or S. marcescens from a sterile site. RESULTS: PFGE
      analysis revealed a highly heterogeneous population of isolates. Bivariate
      analysis of patient-related risk factors revealed duration of central lines,
      respiratory colonization, being a burn patient, and the use of gentamicin or
      nafcillin to be significantly associated with invasive disease. Both respiratory
      colonization and duration of central lines remained statistically significant in
      a multivariate analysis. Staffing data suggested a temporal correlation between
      understaffing and the outbreak period. CONCLUSIONS: Molecular epidemiological
      techniques provided a rapid means of ruling out a point source or significant
      cross-contamination as modes of transmission. In this setting, patient-related
      risk factors, such as respiratory colonization and duration of central lines, may
      provide a focus for heightened surveillance, infection control measures, and
      empirical therapy during outbreaks caused by common nosocomial pathogens. In
      addition, understaffing of nurses may have played a role in this outbreak,
      highlighting the importance of monitoring staffing levels.

PMID- 10926400
TI  - Tax one orthopedists.

PMID- 10926399
TI  - Neonatal group B streptococcal disease: how infection control teams can
      contribute to prevention efforts.
AB  - Group B streptococcal (GBS) disease is a leading cause of morbidity and mortality
      among newborns. Many cases of newborn GBS disease can be prevented by the
      administration of intrapartum antibiotic prophylaxis. Current consensus
      guidelines for prevention of perinatal GBS disease have led to substantial
      declines in the incidence of GBS disease occurring in newborns <7 days of age
      (early-onset disease). Despite declines in the incidence of early-onset disease,
      approximately 20% of pregnant women are colonized with GBS at the time of labor
      and thus have the risk of transmitting the bacteria to their newborns.
      Consequently, continued and improved implementation of prevention efforts is
      essential. Infection control teams can contribute uniquely to prevention of
      perinatal GBS disease by serving as hospital champions of GBS disease prevention.
      In particular, teams can coordinate with administration and staff to encourage
      establishment and effective implementation of GBS prevention policies; facilitate
      improved laboratory processing of prenatal GBS screening specimens; monitor any
      adverse consequences of increased use of intrapartum antibiotics within the
      hospital; and investigate GBS cases that occur to determine whether they could
      have been prevented. By spearheading efforts to improve implementation of
      perinatal GBS disease prevention at the hospital level, hospital epidemiologists
      and infection control practitioners can play an important role in reducing the
      burden of early-onset GBS disease.

PMID- 10926401
TI  - Thoracolumbar pseudarthrosis.
AB  - Pseudarthrosis is the leading cause of failed spine fusion and is of paramount
      concern to surgeons attempting fusion procedures. Thus, it is essential to
      understand this complication to direct efficient and intelligent management. A
      review of various modalities in the identification and diagnosis of a
      pseudarthrosis is presented. In addition, its histologic features and
      classification system are discussed. Not all pseudarthroses need treatment. When
      treatment is considered, however, there are both nonoperative and operative
      strategies. Operative alternatives include posterolateral, anterior, or anterior
      posterior combined fusions.

PMID- 10926402
TI  - Segmental limb reconstruction after tumor resection.
AB  - Limb salvage of large segmental and osteoarticular defects after tumor resection
      has become the standard of care for most patients with musculoskeletal tumors
      because overall survival is the same when compared with that seen in amputation
      patients. This study examines limb salvage for the surgical management of large
      segmental defects in terms of local recurrence, complications, and functional
      outcome in both primary and metastatic lesions. We retrospectively identified 32
      patients with benign or malignant tumors of bone who underwent resection and limb
      salvage reconstruction by means of a custom or modular metal implant between 1985
      and 1995. The most common tumor sites were the proximal femur (41%), distal femur
      (37.5%), and proximal humerus (12.5%). Primary bone lesions accounted for 18
      patients (56%); metastatic disease accounted for 14 patients (44%). Osteosarcoma
      (n = 11) and chondrosarcoma (n = 3) were the most frequent primary tumors. The
      overall limb salvage rate (91%) was high, yet complications (28%) were common.
      Except for 3 patients who underwent amputation after prosthetic failure, all
      surviving patients were independent with or without assistive devices at latest
      follow-up. In patients with advanced metastatic disease, average survival was 7.6
      months. No cases of aseptic loosening or implant breakage were observed in
      patients followed up for 2 years or more. Treatment after tumor resection with a
      limb salvage prosthetic reconstruction has shown good functional outcomes with an
      acceptable complication rate. This modality, therefore, offers patients a more
      favorable functional outcome with a more energy-efficient gait when compared with
      limb amputation.

PMID- 10926403
TI  - Evaluation of tendon-to-bone reattachment: a rabbit model.
AB  - Two different tendon-to-bone reattachment methods were compared to assess tensile
      strength and histologic repair. After sharp dissection, rabbit Achilles tendons
      were reattached to the calcaneus by one of two methods: to abraded cortical bone
      (group 1) or into a cancellous bone tunnel (group 2). After surgery, each rabbit
      had its long-leg hip spica-cast in plantar flexion for 3 weeks. The rabbits'
      tendon-bone junctions were harvested 1, 2, 4, 6, and 12 weeks after surgery.
      Three rabbits were used for each repair method at each point in time: 2 for
      strength testing and 1 for histologic analysis. After this preliminary study,
      tensile strength was tested with another 14 rabbits 2 weeks after surgery. At
      each advancing point in time, in both groups, increasing tendon-bone strength was
      found. Ultimate tensile strength was equivalent for test rabbits (both methods
      after 6 weeks) and control rabbits. There was no significant difference between
      methods at any point in time. Blinded pathologic evaluation reported similar
      healing with both methods over time. With both methods, healing occurred with
      Sharpey fibers attached to the superficial cortex, with tendon resorption
      occurring in the bone tunnel. The simple method of cortical reattachment was
      shown to be equal to the more complex bone-tunnel reattachment.

PMID- 10926404
TI  - Monoarticular acromioclavicular joint gout: a case report.
AB  - Acromioclavicular joint gout is extremely rare. The case presented represents the
      first case of monoarticular acromioclavicular joint gout reported. It is also the
      first reported case of acromioclavicular joint gout in an immunosuppressed
      patient. The diagnostic pitfalls inherent in the evaluation of acute
      monoarticular arthritis in an immunosuppressed patient are illustrated.
      Furthermore, the case demonstrates one of the atypical presentations of gout that
      may occur in renal transplant patients taking cyclosporin A.

PMID- 10926405
TI  - Rapidly destructive hip disease: a case report and review of the literature.
AB  - Rapidly destructive hip disease (RDHD) is an arthropathy of unknown cause that
      involves rapid and total deterioration of both the acetabular and femoral aspects
      of the hip joint. We report a case in which radiographs taken 6 weeks apart
      vividly and poignantly demonstrate the rapidity of the disease. Because there is
      little in the orthopedic literature regarding RDHD, we would like orthopedic
      surgeons to be aware of the condition and the importance of repeat radiographs
      for patients with continued severe hip pain without an apparent cause.

PMID- 10926406
TI  - Familial Mediterranean fever.
AB  - Familial Mediterranean fever (FMF) is an inherited multisystem disease manifested
      by painful, febrile attacks affecting the chest, abdomen, joints, and skin. No
      simple studies confirm the presence of FMF, contributing to the difficulty in
      diagnosis. A 10-year-old boy initially presented with a diffuse rash and
      complaints of bilateral joint pain of the hips, knees, and ankles and pain of the
      right shoulder. The child responded to daily naproxen. One year later, he
      continued to complain of hip, knee, ankle, and bilateral wrist pain. He also
      reported mild to moderate recurrent abdominal discomfort. Omeprazole provided
      intermittent relief. The patient continued to experience episodes of joint and
      abdominal pain. Two and a half years after he first presented, FMF was
      considered. In the second case, a 51-year-old man presented to the emergency
      department with complaints of fever, cough, and abdominal and joint pain. Fever,
      joint pain, and swelling decreased during the next few days. The patient was
      maintained on colchicine, with complete resolution of joint pain complaints
      during the next few days. Colchicine, 1 to 2 mg per day taken continuously during
      flare and quiescent periods, is the treatment of choice for FMF. Colchicine
      reduced the severity and frequency of attacks and may also delay or prevent
      secondary amyloidosis.

PMID- 10926407
TI  - Cervical motion after adding a posterior pad to the halo vest.
AB  - Investigators have shown that significant segmental motion occurs in patients
      immobilized in halo vests. One cadaver study showed that this is decreased with a
      posterior pad added to the construct. To improve nonoperative care of patients
      with cervical trauma, segmental cervical motion was evaluated in normal
      volunteers immobilized in a halo vest with and without a posterior pad. Two
      commonly used methods to measure sagittal angulation were used. Thirty normal
      volunteers were placed in halo vests by using positioning pins on the cranium. A
      sphygmomanometer attached to the posterior uprights of the vest inflated to 40 mm
      Hg was used as a posterior pad at the greatest visible lordosis. Lateral
      radiographs of the cervical spine were taken with volunteers in the upright and
      supine positions with and without the posterior pad inflated. Radiographs were
      randomly sorted and were each read twice by 3 readers. Measurements of the
      posterior atlantodental interval, sagittal displacement, and sagittal rotation
      were recorded using 2 different methods: the Buetti-Bauml method, which uses
      lines drawn along the posterior vertebral bodies, and the method of White and
      colleagues, which uses lines drawn along the inferior vertebral bodies. Inflation
      status of the pad showed no statistically significant difference in any of the
      measured variables. This was true for both methods of measurement. Application of
      a posterior pad to the halo vest did not show any change in the segmental motion
      of the cervical spine in normal volunteers.

PMID- 10926408
TI  - A simple and useful method of follow-up after diagnostic and therapeutic
      injections.
AB  - Accurate follow-up after diagnostic and therapeutic injections is extremely
      important in orthopedic surgery. We describe a simple, inexpensive, and
      convenient method of obtaining such follow-up in a precise and easy-to-interpret
      way. A case example is given in which this information was useful to the
      physician and patient.

PMID- 10926409
TI  - Stress fracture.

PMID- 10926410
TI  - The pathophysiology of chronic heart failure.
AB  - Although the reduction in cardiac function is the cause and central abnormality
      of heart failure, there is clearly a very wide range of abnormalities in other
      systems that contribute to both the symptoms and progression of the syndrome of
      CHF. We must be aware of these changes to use the available therapeutic options
      to maximal effect, as well as being aware that more effective novel treatment
      strategies await a better understanding of the cause and effect of these
      noncardiac abnormalities that constitute the syndrome of CHF.

PMID- 10926411
TI  - Surgery for heart failure: options and outcomes.

PMID- 10926412
TI  - Blood pumps for circulatory support.

PMID- 10926413
TI  - Device selection in mechanical circulatory support.

PMID- 10926414
TI  - New implantable blood pumps for medium and long-term circulatory support.

PMID- 10926415
TI  - Complications of circulatory assist.

PMID- 10926416
TI  - Immunoadsorption as a new treatment option for patients with idiopathic dilated
      cardiomyopathy.

PMID- 10926417
TI  - The Medos ventricular assist device system.

PMID- 10926418
TI  - HeartMate family of left ventricular assist systems.

PMID- 10926419
TI  - The Novacor electrical implantable left ventricular assist system.

PMID- 10926420
TI  - The Thoratec ventricular assist device system.

PMID- 10926421
TI  - The Abiomed BVS 5000 biventricular support system.

PMID- 10926422
TI  - Left ventricular assist devices in the community.

PMID- 10926423
TI  - To pump or not to pump?

PMID- 10926424
TI  - Surgical alternatives to mechanical support.

PMID- 10926425
TI  - The 'Berlin Heart' assist device.

PMID- 10926426
TI  - Orthodontic faculty--a modest proposal.

PMID- 10926427
TI  - Re: epithelial-mesenchymal transformation, palatogenesis and cleft palate.

PMID- 10926428
TI  - Does bite-jumping damage the TMJ? A prospective longitudinal clinical and MRI
      study of Herbst patients.
AB  - The aim of this prospective longitudinal study of 62 consecutively treated Class
      II malocclusions was to determine whether bite-jumping causes temporomandibular
      disorders (TMD). The function of the temporomandibular joint (TMJ) was assessed
      anamnestically, clinically, and by means of magnetic resonance images (MRIs)
      taken before (T1), after (T2), and 1 year after (T3) Herbst treatment. Average
      treatment time with the Herbst appliance was 7.2 months. In all subjects, Herbst
      treatment resulted in a Class I or overcorrected Class I dental arch
      relationship. Thereafter, treatment was continued with a multibracket appliance.
      The condyle was positioned significantly forward during treatment but returned to
      its original position after removal of the Herbst appliance. A temporary
      capsulitis of the inferior stratum of the posterior attachment was induced during
      treatment. Over the entire observation period from before treatment to 1 year
      after treatment, bite-jumping with the Herbst appliance: (1) did not result in
      any muscular TMD; (2) reduced the prevalence of capsulitis and structural
      condylar bony changes; (3) did not induce disc displacement in subjects with a
      physiologic pretreatment disc position; (4) resulted in a stable repositioning of
      the disc in subjects with a pretreatment partial disc displacement with
      reduction; and (5) could not recapture the disc in subjects with a pretreatment
      total disc displacement with or without reduction. A pretreatment total disc
      displacement with or without reduction did not, however, seem to be a
      contraindication for Herbst treatment. In conclusion, bite-jumping using the
      Herbst appliance does not have a deleterious effect on TMJ function and does not
      induce TMD on a short-term basis.

PMID- 10926429
TI  - A comparative study of two methods of quantifying the soft tissue profile.
AB  - One of the most important components of orthodontic diagnosis is the evaluation
      of the patient's soft tissue profile. There have been many attempts to quantify
      the soft tissue profile based on the lateral cephalogram. Yet, the methodology
      used to evaluate the profile varies widely among studies, and there has been no
      consistency in the way straight lines are constructed in the analysis of the soft
      tissue contours. The purpose of the current study was to compare the values
      obtained by 2 drawing methods (tangent line and anatomic points) of constructing
      angles, and to assess the intraobserver and interobserver reproducibility for
      both methods. There were statistically significant differences between the 2
      methods for 9 of the 10 measurements evaluated. In the comparison of
      reproducibility assessed by Pearson correlation analysis, both methods showed
      statistically significant correlations between repeated measurements. The
      anatomic point method, however, showed greater reproducibility by means of a
      paired t-test. In the analysis of intraobserver reproducibility, 2 measurements
      showed significant differences with the anatomic point method and 4 measurements
      demonstrated significant differences when the tangent line method was used. In
      the analysis of interobserver reproducibility, 5 measurements showed significant
      differences in the anatomic point method, while 6 measurements represented
      significant differences in the tangent line method. Our results indicate that a
      precise description of the methodology used in the analysis of the soft tissue
      must be provided because of the differences between methods. In the analysis of
      soft tissue contours, the construction of lines with the anatomic point method is
      more reproducible than the tangent line method.

PMID- 10926430
TI  - Long-term profile changes associated with successfully treated extraction and
      nonextraction Class II Division 1 malocclusions.
AB  - This study was undertaken to compare the post-treatment and long-term soft tissue
      profiles of successfully managed and stable Class II, division 1 malocclusions
      treated with either 4 first premolar extractions or nonextraction therapy. It was
      hypothesized that, if sound extraction decisions were made according to accepted
      treatment objectives and successful treatment outcomes were achieved, there
      should be no differences between groups in soft tissue profiles post-treatment
      and long-term post-retention. The sample consisted of 63 Caucasian adolescents
      (23 extraction, 40 nonextraction). Correction of the malocclusion was achieved
      using a combination of cervical headgear concurrent with mandibular growth and
      maxillary incisor retraction. Pretreatment, post-treatment, and long-term post
      retention lateral cephalometric radiographs were evaluated. The soft tissue
      facial profiles of the extraction and nonextraction samples were the same
      following active treatment and long-term post-retention. Progressive flattening
      of the facial profile was observed in both samples. This flattening was
      attributed to the maturational changes associated with continued mandibular
      growth and nasal development and was not influenced by whether or not teeth were
      removed. Long-term lip positions were more retrusive than the ideals suggested by
      Ricketts and Steiner, but close to the values reported for normal, untreated
      adults of similar ages. The pretreatment position and thickness of the lower lip
      as well as the initial maxillomandibular skeletal relationship may be predictors
      of post-treatment or long-term lower lip position.

PMID- 10926431
TI  - Long-term prognosis of BSSO mandibular relapse and its relation to different
      facial types.
AB  - The bilateral sagittal split osteotomy (BSSO) has evolved into an effective and
      preferred surgical procedure for mandibular setbacks. As with all surgical
      procedures designed to setback the mandible, relapse occasionally occurs after
      BSSO procedures. Several factors have been suggested to play a contributory role
      in this relapse. The present study was performed to determine the stability of
      the mandibular position over the course of long-term observation. Different
      facial patterns that could potentially be used as predictors of relapse were
      examined. The study included cases of skeletal mandibular prognathism, with the
      patient in each case having undergone surgical correction involving a BSSO at
      least 5 years prior to the study. Lateral cephalograms were analyzed in order to
      classify facial patterns. Angular and linear cephalometric measurements,
      consisting of SN-Pogonion angle, SN-occlusal plane angle, and Pogonion depth and
      height, were compared at 1 year postoperatively and at the long-term follow-up. A
      significant correlation between facial type and relapse pattern was confirmed at
      the long-term assessment of prognosis.

PMID- 10926432
TI  - External apical root resorption following orthodontic treatment.
AB  - This study investigated the association of appliance type and tooth extraction
      with the incidence of external apical root resorption (EARR) of posterior teeth
      following orthodontic treatment. Pre- and posttreatment orthopantomograms were
      compared for 97 patients and a 4-grade ordinal scale used to measure EARR. The
      incidence of EARR was positively associated with tooth position (P < .001),
      appliance type (P = .038), and extractions (P = .001). This was observed in an
      overall analysis mutually adjusted for the effects of age at start of treatment,
      pretreatment overbite and overjet, use of headgear, tooth extraction, and type of
      appliance. The incidence of EARR was 2.30 times higher for Begg appliances
      compared with edgewise, and it was 3.72 times higher where extractions were
      performed.

PMID- 10926434
TI  - The influence of orthodontic adhesive properties on the quality of orthodontic
      attachment.
AB  - The objective of this study was to determine the resilience, glass transition
      temperature (Tg), ultimate flexural strength (UFS), and penetration coefficient
      of 3 composite adhesives (Concise, Transbond, and Right On) and a glass ionomer
      cement (Fuji Ortho LC). For 25 minutes after initial set, the composite materials
      were significantly more resilient than Fuji Ortho LC (P = .000). Resilience
      values for all materials increased for up to 90 minutes after initial set,
      reflecting a continuation of their setting reaction. Right On remained the most
      resilient material at 90 minutes after initial set (P < or = .01). At 120
      minutes, there was no significant difference in the resilience of Concise, Right
      On, and Fuji Ortho LC. However, Transbond was significantly less resilient than
      these materials (P < or = .01). The composite materials recorded significantly
      higher glass transition values (89-123 degrees C) than Fuji Ortho LC (54 degrees
      C). The composite materials were also significantly stronger (61-68 MPa) than
      Fuji Ortho LC (35 MPa) in flexion. The penetration coefficients of Concise and
      Transbond were significantly higher (P < or = .001) than Right On and Fuji Ortho
      LC. However, the relative penetration coefficients of the materials studied did
      not appear to influence the degree of bracket base penetration achieved by the
      cements. In conclusion, Fuji Ortho LC offered a reduced energy-absorbing capacity
      immediately after bracket placement and reduced cohesive and mechanical adhesive
      strength. In addition, the glass transition temperature of Fuji Ortho LC was low;
      this may result in compromised attachment at temperatures above 60 degrees C.
      Significant differences in the penetration coefficient of the materials studied
      have been recorded. However, the penetration of the 4 cements into a range of
      bracket base morphologies was uniformly good. Therefore, the differences in
      penetration coefficient recorded should not influence the quality of the bracket
      cement interface provided.

PMID- 10926433
TI  - A comparative clinical trial of a compomer and a resin adhesive for orthodontic
      bonding.
AB  - The study aimed to compare the survival time and cariostatic potential of a
      compomer to that of a resin adhesive when used to bond stainless steel
      orthodontic brackets to labial segment teeth only. The effect of the patients'
      sex, age at the start of treatment and presenting malocclusion on bracket
      survival time was assessed also. Forty-five consecutive patients who attended for
      fixed appliance therapy were randomly selected. Four hundred twenty-six brackets
      were bonded (213 with compomer and 213 with resin adhesive) with a split mouth
      design; the right or left side allocation of compomer in either arch was
      alternated. Color transparencies of the maxillary incisors, mandibular incisors,
      or both, and transparencies of the canines, were taken before treatment. At the
      debond stage, the transparencies were projected (20x) and assessed by an
      experienced examiner, who used a caries index. The survival time distributions
      for brackets bonded with each bonding agent were not significantly different (P =
      .74, paired Prentice-Wilcoxon test; P = .75, Akritas test), with bracket failure
      rates of 17% and 20% recorded for compomer and resin adhesive, respectively.
      Neither the patients' sex (P = .85) nor malocclusion (P = .26) appear to affect
      significantly bracket survival, but patient age was identified as a useful
      prognostic indicator of bracket survival (P < .001). On average, there was more
      decalcification related to brackets bonded with resin adhesive than with compomer
      (P = .0075). Survival time distributions of brackets bonded with compomer or
      resin adhesive appear comparable, but decalcification was reduced significantly
      by bonding with compomer.

PMID- 10926435
TI  - Case report: orthodontic and dentofacial orthopedic considerations in Apert's
      syndrome.
AB  - Apert's syndrome is a developmental malformation characterized by:
      craniosynostosis, a cone-shaped calvarium, midface hypoplasia, pharyngeal
      attenuation, ocular manifestations, and syndactyly of the hands and feet. The
      prodromal characteristic for the typical craniofacial appearance is early
      craniosynostosis of the coronal suture, the cranial base, and an agenesis of the
      sagittal suture. These craniofacial characteristics predispose the patient to
      maxillary transverse and sagittal hypoplasia with concomitant dental crowding, a
      maxillary pseudocleft palate, and a skeletal and dental anterior open bite. This
      is a case report of an Apert's syndrome patient with a discussion of the
      orthodontic and dentofacial orthopedic considerations that influenced the
      treatment plan.

PMID- 10926436
TI  - Osseointegrated implants as an adjunct to facemask therapy: a case report.
AB  - Branemark Implants were placed in the zygomatic buttresses of the maxilla in a 12
      year and 1-month-old female patient with a Class III malocclusion caused by
      maxillary growth retardation secondary to repair of a unilateral cleft lip and
      palate defect. The implants were left to integrate for 6 months followed by
      placement of customized abutments that projected into the buccal sulcus. Elastic
      traction (400 g per side) was applied from a facemask to the implants at 30
      degrees to the occlusal plane for 14 hours per day for 8 months (ages 12 years
      and 10 months to 13 years and 6 months). The maxilla moved downward and forward 4
      mm rotating anteriorly as it was displaced. The change in the maxillary occlusal
      plane resulted in a secondary opening of the mandible. There was a 2 degrees
      increase in the SN-mandibular plane angle and an increase in nasion to menton
      distance of 9 mm. Clinically, this resulted in an increase in fullness of the
      infraorbital region and correction of the pretreatment mandibular prognathism.
      There was an increase in nasal prominence as the maxilla advanced. This
      contributed to the increase in facial convexity. The secondary dental change
      frequently seen in standard facemask therapy was avoided. The displacement of the
      maxilla was stable 1 year beyond cessation of facemask therapy. The patient's
      midface profile was improved by age of 13 years and 6 months. Details of the
      clinical procedure and treatment changes are presented.

PMID- 10926437
TI  - Prophylaxis and treatment of fungal infections associated with haematological
      malignancies.
AB  - Patients with haematological malignancies form one of the most susceptible host
      groups for microbial infection, especially during neutropenia. The incidence of
      invasive fungal infections has increased in recent years, highlighting the need
      for better diagnosis and more effective antifungal therapies. Amphotericin B is
      the drug of choice for many fungal infections, although toxicity and the need for
      intravenous infusion restrict its use. When possible, oral administration of
      antifungal agents is preferable but intravenous administration is often needed
      and current oral agents have their limitations: fluconazole because of a narrow
      spectrum of activity; itraconazole capsules because of erratic absorption. In
      this review, prophylactic and treatment options for systemic fungal infections
      are discussed. The specific needs of patients with different types of leukaemia
      and the benefits of new amphotericin B and itraconazole formulations are
      examined.

PMID- 10926438
TI  - Antibiotic treatment for acute otitis media.
AB  - The major problems encountered in the antibiotic therapy of acute otitis media
      (AOM) are the tremendous increase in the resistance to antibiotics of its main
      pathogens and the lack of tight criteria (taking into consideration, as a major
      determinant, the eradication of the pathogens from the middle ear fluid) in the
      selection of the appropriate antibiotic drugs for the treatment of this disease.
      Future drugs for the treatment of AOM will have to be approved only after their
      in vivo microbiological efficacy for each major pathogen is documented. This
      documentation will be provided by more antibiotic studies with bacteriological
      outcome using the double-tympanocentesis method and stratifying the AOM patients
      by age and initial clinical severity. Judicious use of antibiotics for the
      treatment of AOM will have a major impact on society, leading to a less frequent
      but more skilled administration of the most effective drugs.

PMID- 10926439
TI  - Sir Edward Abraham's contribution to the development of the cephalosporins: a
      reassessment.
AB  - This paper is based on an invited lecture given at the 21st International
      Congress of Chemotherapy in July 1999, as part of a Symposium entitled '50 years
      of cephalosporins: their use the next 50 years', (Hamilton-Miller JMT,
      Cephalosporins: from mould to drug. Sardinia to Oxford and beyond, J Antimicr
      Chemother 1999;44(A):26). Celebration of this Golden Anniversary was made more
      poignant by the death of the last major participant, Sir Edward Abraham, in May
      1999. This history has been told before, but mainly by Sir Edward, who being a
      very modest man (to which his obituaries graphically attest) consistently
      underplayed the role that he and Newton had in the discovery of cephalosporin C,
      that led to all the cephalosporins now in use. I had the privilege of working at
      the Dunn School from 1967 to 1970, with Abraham and Newton, where I met Brotzu,
      Florey and Dorothy Hodgkin, all of whom had important roles in this story. Other
      workers at the Dunn School at that time, e.g. Heatley, Sanders and Jennings (who
      became Lady Florey), helped develop penicillin. Such a galaxy of stars of the
      antibiotic firmament will never again be assembled. "Let us now praise famous
      men... these were honoured in their generation, and were the glory of their
      times" - Ecclesiasticus XLIV. vv 1.7.

PMID- 10926440
TI  - Population pharmacokinetics of tobramycin in hospitalized patients receiving once
      daily dosing regimen.
AB  - The population pharmacokinetics of tobramycin was investigated in a group of 327
      adult hospitalized patients receiving once-daily administration of tobramycin at
      a dose of 7 mg kg(-1). The patients had an average age of 57+/-18 y and an
      average weight of 65+/-14 kg; 153 of the patients were female. Data, comprised of
      575 serum concentrations, were analyzed using a nonlinear mixed-effect model
      (NONMEM) with a first-order conditional estimation method and were best described
      with a one-compartment model. The patient covariates including body weight,
      gender, age and creatinine clearance (CL(CR)) were added in a stepwise fashion to
      identify their potential influences on tobramycin pharmacokinetics. Results
      showed that tobramycin clearance (CL) was linearly correlated with CL(CR)
      (proportionality constant: 0.066+/-0.002 x CL(CR) (ml min(-1))) and the volume of
      distribution (Vd) was linearly related to body weight (proportionality constant:
      0.40+/-0.024 x body weight (1 kg(-1))). The mean population estimates for CL and
      Vd were 4.53 l h(-1) and 27.3 l, respectively. The half-life of tobramycin was
      estimated to be 4.2 h. The inter-individual variability in CL and Vd were 37.0
      and 28.5%, respectively. The residual error was 1.2 mg l(-1). Based on the
      results, optimal dosing intervals for renal impaired patients were calculated and
      were comparable with the intervals derived from the previous established
      nomogram.

PMID- 10926441
TI  - Modification of acquired immunity in BALB/c mice by aztreonam.
AB  - Recent studies have suggested that antibiotics may act as biological response
      modifiers. In this study we investigated the effect of aztreonam, a monobactam
      antibiotic, on different parameters of acquired immunity in BALB/c mice.
      Different dosages of aztreonam injected into mice induced an increase in the
      lymphoproliferative response to specific mitogens and in the production of
      interleukin-2 by splenic cells, as well as a decreased response of this immune
      population to sheep erythrocytes lower total blood cell counts and a lower
      percentage of monocytes than in untreated mice. These results show a modulatory
      action of aztreonam on different immune parameters, which is independent of its
      antimicrobial activity and that could be of interest in human therapy.

PMID- 10926442
TI  - Uptake and intracellular activity of ofloxacin isomers in human phagocytic and
      non-phagocytic cells.
AB  - The penetration and intracellular activity of ofloxacin and its isomers
      (levofloxacin and D-ofloxacin) into human polymorphonuclear leucocytes (PMN),
      human peritoneal macrophages (PMphi) and tissue cultured epithelial cells (McCoy)
      were evaluated. The cellular to extracellular concentration (C/E) values of the
      three fluoroquinolones were higher than 3.6 and 2.6 in PMN and PMphi,
      respectively. The C/E ratios in McCoy cells were lower than those in PMN, but
      still higher than 2.0. The uptake of ofloxacin and its isomers was rapid, non
      saturable and reversible. All quinolones (extracellular concentrations: 2, 5 and
      10 mg/l) produced a significant reduction of viable intraphagocytic
      Staphylococcus aureus in phagocytic cells. We concluded that ofloxacin and its
      isomers reach high intracellular concentrations in phagocytic and non phagocytic
      cells while remaining active in the former.

PMID- 10926443
TI  - Influence of a prophylactic single dose of ciprofloxacin on the level of
      resistance of Escherichia coli to fluoroquinolones in urology.
AB  - During the years 1991-1996 an increase in fluoroquinolone-resistant Escherichia
      coli was observed at the Urological Department of the Municipal Hospital in
      Straubing, Germany. A prospective study was undertaken to investigate the
      influence of single-dose prophylaxis (SDP) using 500 mg ciprofloxacin orally on
      the level of resistance to ciprofloxacin of faecal E. coli. One hundred and five
      patients were recruited to the study: E. coli resistance to ciprofloxacin before
      prophylaxis was 3% (3/91) in contrast to 12% (5/42) after prophylaxis (P =
      0.052). In 31 isolates no major change in the low MIC values before and after SDP
      was observed. PFGE showed clonal diversity in about half of the cases. Three
      isolates showed low-level resistance and three isolates high-level resistance to
      ciprofloxacin both before and after SDP. PFGE showed clonal identity in all
      cases. All patients had previously been treated with fluoroquinolones (FQ). In
      two isolates emergence of high-level resistance to ciprofloxacin after SDP
      occurred. PFGE showed clonal diversity in both cases. We conclude that after SDP
      with 500 mg ciprofloxacin there is a shift to gram-positive bacteria in the
      faeces and an increase in the rate of FQ resistance. Since selection of highly
      resistant E. coli is possible, a careful risk-benefit evaluation of prophylaxis
      with FQ is indicated.

PMID- 10926444
TI  - In vitro activity of 19 antimicrobial agents against 3513 nosocomial pathogens
      collected from 48 Canadian medical centres. The Canadian Antimicrobial Study
      Group.
AB  - Antimicrobial resistance is a global concern. Differentiation between
      susceptibility rates for nosocomial versus community pathogens is important
      epidemiologically because it impacts on the appropriate empirical selection of
      antimicrobial therapy for infected patients. We studied resistance rates for 3513
      nosocomial pathogens from 48 Canadian medical centres tested against 19
      antimicrobial agents. The following are percent susceptibility for ceftazidime,
      ceftriaxone, ciprofloxacin, imipenem, netilmicin, and ticarcillin/clavulanic
      acid, respectively: Enterobacteriaceae 95, 95, 97, 99 98, 89; Escherichia coli,
      all 99 except ticarcillin/clavulanic acid (91); Enterobacter spp. 78, 78, 96, 99,
      99, 71; Citrobacter spp. 79, 80, 89, 100, 94, 73; Proteus spp. 99, 88, 99, 88,
      99, 98; Pseudomonas aeruginosa 88, 20, 82, 88, 81, 36; Staphylococcus aureus, all
      > 95; Enterococcus spp. 4, 9, 62, 95, 43, 38. Susceptibility rates for other
      species of microorganisms and agents tested varied considerably. Some
      institutions had higher than average resistance rates for some pathogens (i.e. P.
      aeruginosa) and some agents. Detection and continued surveillance of
      antimicrobial resistance amongst nosocomial pathogens is vital to patient care
      and health care resources. The control of antimicrobial resistance can help
      maintain antibiotic usage and costs associated with the use of ever more potent
      drugs and the treatment of increasingly resistant infections.

PMID- 10926445
TI  - Aminoglycoside-modifying enzymes in high-level streptomycin and gentamicin
      resistant Enterococcus spp. in Spain.
AB  - Aminoglycoside resistance was evaluated in 690 enterococcus strains isolated from
      different clinical sources originating from patients at the University Clinic
      Hospital of Zaragoza (Spain). The enterococci obtained from clinically
      significant samples (blood, urine, or exudates) showed more high-level resistance
      to gentamicin and streptomycin (65 and 42%, respectively) than those isolated
      from faecal samples (49 and 23%, respectively). Aminoglycoside-modifying enzymes
      (AME) from 119 of these high-level gentamicin and streptomycin resistant
      enterococcus strains were studied. The most frequent AMEs found were APH(3') and
      AAC(6')-APH(2"). More than one enzyme was detected in 71% of the strains (four
      different enzymes in 5% of the strains). Three Enterococcus faecalis strains had
      ANT(4')(4") enzymatic activity. Different enzymatic expressions of the
      bifunctional enzyme AAC(6')-APH(2") were demonstrated in strains in which the
      complete aac(6')-aph(2") gene was detected by PCR and hybridization: (i) AAC(6')
      + APH(2") activity; (ii) AAC(6') only; (iii) APH(2") only; and (iv) no activity
      of AAC(6') or APH(2").

PMID- 10926446
TI  - Evaluation of gemifloxacin (SB-265805, LB20304a): in vitro activity against over
      6000 gram-positive pathogens from diverse geographic areas.
AB  - Gemifloxacin (GEMI), formerly SB-265805 and LB20304, is a newer fluoroquinolone
      with broad-spectrum activity against a wide variety of bacterial pathogens. The
      present investigation extended earlier observations by sampling an additional
      6790 gram-positive organisms from more than 50 medical centres on three
      continents. The reference broth microdilution method with recommended medium
      supplements was used throughout. Selected results (number strains tested; MIC90
      for GEMI/trovafloxacin in mg/l; % < or = 1 mg/l for GEMI/trovafloxacin) were:
      Staphylococcus aureus (3672; 2/2; 86/85), S. epidermidis (404; 1/>4; 92/71),
      Enterococcus faecalis (630; 4/>4; 76/66), E. faecium (216; > 4/>4; 15/11),
      Streptococcus pneumoniae (300; 0.06/0.25; 100/97), beta-haemolytic streptococci
      (150; 0.06/0.25; 100/100) and viridans group streptococci (150; 0.12/0.25;
      99/97). Gemifloxacin appeared equal or superior to trovafloxacin in its overall
      gram-positive spectrum of activity pending a choice of the susceptible breakpoint
      concentration. Continued in vitro, pharmacodynamic and clinical investigations of
      gemifloxacin appear warranted.

PMID- 10926447
TI  - Antimicrobial resistance of Streptococcus pneumoniae, Haemophilius influenzae and
      Moraxella catarrhalis isolated in Hawaii.

PMID- 10926448
TI  - Systemic chlorellosis, an emerging infection in humans caused by algae.
AB  - One hundred and eight cases of human protothecosis occurring over 25 years are
      reviewed. The most common species isolated was Prototheca wickerhamii, The algae
      have been isolated from a large number of sites but seem to have low virulence.
      In the majority of systemic infections there have been few symptoms. Cutaneous
      manifestations may vary from patient to patient but infections of
      immunosuppressed patients tend to be more florid. Most cases have been
      successfully treated by excising the lesion or with antifungals. Most strains are
      sensitive to 5-fluorocytosine, amphotericin B and the azoles but resistance does
      occur.

PMID- 10926450
TI  - Rifampicin sub-inhibitory concentrations reduce the expression of haemolysin in
      Aeromonas spp.

PMID- 10926449
TI  - Treatment of Chlamydia pneumoniae.

PMID- 10926454
TI  - Polyhalogenated monoterpenes from a tasmanian collection of the red seaweed
      plocamium cartilagineum

PMID- 10926453
TI  - Vinylfurans revisited A new sesquiterpene from euryspongia deliculata

PMID- 10926455
TI  - Bioactive compounds from combretum erythrophyllum

PMID- 10926456
TI  - Morphology and Luminescence of(GdY)(2)O(3):Eu Particles Prepared by Colloidal
      Seed-Assisted Spray Pyrolysis.
AB  - (Gd(x)Y(1-x))(2)O(3):Eu [x=0, 0.25, 0.5, 0.75, 1.0] phosphor particles with 6
      at.% Eu dopant of total concentration were prepared using spray pyrolysis. The
      effects of composition on the morphology, crystallinity, and photoluminescence
      characteristics of composite particles were investigated. The morphological
      control of (Gd(x)Y(1-x))(2)O(3):Eu particles in spray pyrolysis was also
      attempted by using colloidal and aqueous solutions. The particles prepared from
      colloidal solutions containing small amounts of Gd or Y hydroxy carbonate sol as
      seed material had spherical and filled morphology after the post-treatment at
      high temperature. On the other hand, the (Gd(x)Y(1-x))(2)O(3):Eu particles
      prepared from aqueous solutions were hollow and porous after post-treatment in
      all compositions. Particles prepared from colloidal solutions had
      photoluminescence emission intensities higher than those of particles prepared
      from aqueous solutions. Copyright 2000 Academic Press.

PMID- 10926457
TI  - Characterization of a Polydisperse Depletion-Flocculated Emulsion.
AB  - The addition of nonadsorbing polymer to an alkane-in-water emulsion causes the
      droplets to flocculate into a space-spanning, stress-bearing network. We report
      rheological measurements of an emulsion of 1-bromohexadecane-in-water flocculated
      by hydroxy-ethylcellulose. Small-deformation oscillatory measurements allowed
      characterization of the structure during formation and an indication of the
      strength of the resulting network. Emulsions without polymer, and polymer
      solutions alone, showed essentially viscous behavior, with dominant viscous
      modulus over the whole frequency range (0.01-10 Hz). However, the emulsion
      containing polymer demonstrated a significant elastic modulus, dependent on the
      oil and polymer concentrations, attributable to interdroplet depletion
      interactions. Power-law relationships were observed between the elastic modulus,
      elastic strain limit, and oil volume fraction, but the indices were lower than
      those predicted by fractal models, giving unrealistic fractal dimensionalities.
      The modulus increased exponentially with polymer concentration, but the elastic
      strain limit was independent of added polymer. The rate of formation of the
      network was not consistent with diffusion-controlled aggregation. Copyright 2000
      Academic Press.

PMID- 10926458
TI  - Aggregation Properties of Sodium Hyaluronate with Alkanediyl-alpha,omega
      bis(dimethylalkylammonium Bromide) Surfactants in Aqueous Sodium Chloride
      Solution.
AB  - Aggregation properties of sodium hyaluronate (NaHA) with alkanediyl-alpha,omega
      bis(dimethylalkylammonium bromide) surfactants (referred to as dimeric
      surfactants) in aqueous sodium chloride solutions have been studied as a function
      of surfactant chemical structure. Surface tension measurements indicate the
      unusual parabolic dependence of surface tension vs log surfactant concentration
      with a surface tension minimum at concentration c(min). The increase of surface
      tension above c(min) may be related to the formation of clusters consisting of
      NaHA chain and dimeric surfactants at the air-water interface and in the bulk.
      From light scattering measurements, molecular weight, hydrodynamic radius, and
      second virial coefficient have been calculated. The simple calculation of the
      ratio of positive charge of dimeric surfactant unit per one negatively charged
      hyaluronate disaccharidic unit in NaHA-surfactant complex reveals that there is a
      slight excess of positive surfactant charges per one negatively charged
      disaccharidic unit in the region around c(min) and the NaHA-surfactant complex is
      not far from electroneutrality. The nonlinear behavior of viscosity vs surfactant
      concentration in the NaHA-dimeric surfactant system depends on surfactant
      chemical structure. The behavior is concerned with the size increase due to
      complex growth and with the size shrinkage above c(min). A model describing the
      behavior of NaHA-surfactant complex in the bulk and at the interface is
      suggested. Copyright 2000 Academic Press.

PMID- 10926459
TI  - Substrate Morphology and Particle Adhesion in Reacting Systems.
AB  - This paper describes an effort to measure and model changes in the adhesion of
      micron-scale particles to substrates in systems in which chemical reactions are
      occurring. Contact interactions between polystyrene latex spheres and silicon
      substrates (with surface oxide) immersed in aqueous KNO(3) solutions were
      studied. Two important results were obtained. First, it was shown that the AFM
      can be employed to monitor, in situ, changes in adhesive interactions induced by
      surface chemical reactions in this system. Second, the morphology of the
      interacting surfaces plays a controlling role in particle adhesion. In
      particular, for this system, changes in roughness of the substrate changed the
      interaction force by nearly 90%. Copyright 2000 Academic Press.

PMID- 10926460
TI  - Characteristics of Nonafluorobutyl Methyl Ether (NFE) Adsorption onto Activated
      Carbon Fibers and Different-Size-Activated Carbon Particles.
AB  - The characteristics of adsorption of 1,1,1,2,2,3,3,4,4-nonafluorobutyl methyl
      ether (NFE), a chlorofluorocarbon (CFC) replacement, onto six different activated
      carbon; preparations (three activated carbon fibers and three different-sized
      activated carbon particles) were investigated to evaluate the interaction between
      activated carbon surfaces and NFE. The amount of NFE adsorbed onto the three
      activated carbon fibers increased with increasing specific surface area and pore
      volume. The amount of NFE adsorbed onto the three different-sized-activated
      carbon particles increased with an increase in the particle diameter of the
      granular activated carbon. The differential heat of the NFE adsorption onto three
      activated carbon fibers depended on the porosity structure of the activated
      carbon fibers. The adsorption rate of NFE was also investigated in order to
      evaluate the efficiency of NFE recovery by the activated carbon surface. The
      Sameshima equation was used to obtain the isotherms of NFE adsorption onto the
      activated carbon fibers and different-sized-activated carbon particles. The rate
      constant k for NFE adsorption onto activated carbon fibers was larger for
      increased specific surface area and pore volume. The rate of NFE adsorption on
      activated carbons of three different particle sizes decreased with increasing
      particle diameter at a low initial pressure. The adsorption isotherms of NFE for
      the six activated carbons conformed to the Dubinin-Radushkevich equation; the
      constants BE(0) (the affinity between adsorbate and adsorbent) and W(0) (the
      adsorption capacity) were calculated. These results indicated that the
      interaction between the activated carbon and NFE was larger with the smaller
      specific surface area of the activated carbon fibers and with the smaller
      particle diameter of the different-sized-activated carbon particles. The degree
      of packing of NFE in the pores of the activated carbon fibers was greater than
      that in the pores of the granular activated carbons. Copyright 2000 Academic
      Press.

PMID- 10926461
TI  - Thermodynamics of the Laminar Donnan System.
AB  - Thermodynamic quantities of a polyelectroyte immersed in salt solution are
      derived modeling the polyelectrolyte by a sequence of charged parallel flat
      plates. The starting point for the analysis is the derivation of the Gibbs free
      enthalpy in its canonic variables pressure (p) and temperature (T), i.e., as a
      thermodynamic potential. From this, further thermodynamic quantities such as
      Helmoltz free energy, entropy, internal energy, compressibility, isobar and
      isochor heat capacities, and expansive force are derived in analytical
      expressions by differentiation. All these formulas contain the parameter plate
      surface charge density (sigma) that provides a measure of the discontinuity of
      the polymer charge distribution that can be used to fit the theory to
      experimental data. Thermodynamic quantities are also known from the classical
      Donnan equilibrium that treats the polyelectroyte charge network as a charge
      continuum. A limiting process is used to perform the transition from the laminar
      Poisson- Boltzmann model to the continuous Donnan equilibrium. In general, the
      expressions of the Donnan system are recovered for plate charge density sigma-
      >0, number of plates Z-->infinity, and sigma Z=constant. Copyright 2000 Academic
      Press.

PMID- 10926462
TI  - Modeling of Copper(II), Cadmium(II), and Lead(II) Adsorption on Red Mud from
      Metal-EDTA Mixture Solutions.
AB  - The adsorption of toxic heavy metal cations, i.e., Cu(II), Cd(II), and Pb(II),
      from metal-EDTA mixture solutions on a composite adsorbent having a heterogeneous
      surface, i.e., bauxite waste red mud, has been investigated and modeled with the
      aid of a modified surface complexation approach in respect to pH and complexant
      dependency of heavy metal adsorption. EDTA was selected as the modeling ligand in
      view of its wide usage as an anthropogenic chelating agent and abundance in
      natural waters. The adsorption experiments were conducted for metal salts
      (nitrates), metal-EDTA complexes alone, or in mixtures containing (metal+metal
      EDTA). The adsorption equilibrium constants for the metal ions and metal-EDTA
      complexes were calculated. For all studied cases, the solid adsorbent phase
      concentrations of the adsorbed metal and metal-EDTA complexes were found by using
      the derived model equations with excellent compatibility of experimental and
      theoretically generated adsorption isotherms. The model was useful for metal and
      metal-EDTA mixture solutions either at their natural pH of equilibration with the
      sorbent, or after pH elevation with NaOH titration up to a certain pH. Thus
      adsorption of every single species (M(2+) or MY(2-)) or of possible mixtures
      (M(2+)+MY(2-)) at natural pH or after NaOH titration could be calculated by the
      use of simple quadratic model equations, once the initial concentrations of the
      corresponding species, i.e., [M(2+)](0) or [MY(2-)](0), were known. The
      compatibility of theoretical and experimental data pairs of adsorbed species
      concentrations was verified by means of nonlinear regression analysis. The
      findings of this study can be further developed so as to serve environmental risk
      assessment concerning the expansion of a heavy metal contaminant plume with
      groundwater move ment in soil consisting of hydrated-oxide type minerals.
      Copyright 2000 Academic Press.

PMID- 10926463
TI  - Interactions of Pyrene-Labeled Silica Particles.
AB  - Silica spheres were prepared by the Stober method, and the method of labeling
      with pyrene, using aminopropylysilane as the linking agent, was optimized.
      Excimers between particles were formed when high concentrations of label were
      used. Both surfactant and polyelectrolyte addition were able to cause floc
      formation when added to suspensions of the silica, but only the surfactant
      changed the I(1)/I(3) ratio and diminished excimer formation. Copyright 2000
      Academic Press.

PMID- 10926464
TI  - Preparation and Characterization of Uniform Needle-like Particles of Nickel Basic
      Sulfate.
AB  - Needle-like particles (maximum length, approximately 2 um) of nickel basic
      sulfate (Ni(OH)(1.4)(SO(4))(0.3)) were prepared by forced hydrolysis at 100
      degrees C for 2 days of aqueous solutions containing nickel(II) nitrate,
      nickel(II) sulfate, and sodium acetate in the appropriated concentrations. The
      needles were characterized in terms of their composition, crystal structure, and
      electrokinetic behavior. Their structural and compositional evolutions with
      temperature were also studied. It was found that a dehydroxylation process took
      place on heating at 500 degrees C after which the particles consisted of a
      mixture of crystalline NiO and an amorphous nickel sulfate. This compound
      decomposed at a higher temperature (800 degrees C) yielding NiO. The particles
      lost the needle-like shape after calcination at 500 degrees C. Copyright 2000
      Academic Press.

PMID- 10926465
TI  - Dynamics of Capillary Rise.
AB  - An overview and detailed analysis of the classical theory of capillarity is
      presented. A number of known equations of capillary rise dynamics are shown to be
      different limiting cases of one rather general equation. Some internal
      inconsistencies of the classical equations are pointed out. The role of nonlinear
      dissipation and flow pattern effects in the front zone of the liquid column and
      near the capillary entrance is discussed. Numerical simulations and experimental
      data demonstrating some characteristic types of dynamic behavior predicted by the
      theory are reported. Special attention is paid to the capillary rise of
      surfactant solutions. As applied to this special case, the existing theory is
      substantially elaborated by setting up a closed system of equations describing
      the surfactant transport and relaxation processes in the adsorption layer. A
      simplified relation for the capillary rise dynamics in the case of strong
      depletion of the interfacial region is obtained, which is in qualitative
      agreement with the experimental behavior. Copyright 2000 Academic Press.

PMID- 10926466
TI  - Modeling of the Permeate Flux during Microfiltration of BSA-Adsorbed Microspheres
      in a Stirred Cell.
AB  - A study on the variation of the permeate flux was performed in a stirred cell
      charged with microspheres, to investigate the effects of the stirrer speeds (300,
      400, and 600 rpm) and the BSA concentration (0.1, 0.2, 0.4, and 0.8 g/L) under
      constant pressure. The permeate flux increased over time before the saturation
      point, but it began to decrease after that point. An increase of the BSA
      concentration and the stirrer speed resulted in the rapid increase of the
      permeate flux. This is contrary to the observation of the conventional filtration
      experiments using a stirred cell. A resistance-in-series model was employed for
      the modeling of the permeate flux. The cake resistance (R(c), induced by the
      concentration polarization of microspheres) and the fouling resistance (R(f),
      induced by the adsorption of BSA inside the membrane pore) must be considered
      simultaneously for the modeling. These modeling results were in good agreement
      with the experimental data. These can be applied to the special system
      considering both R(c) and R(f) as well as the general filtration systems using a
      stirred cell. Copyright 2000 Academic Press.

PMID- 10926467
TI  - Substituent Distribution in Cellulose Acetates: Its Control and the Effect on
      Structure Formation in Solution.
AB  - Architecture-regulated cellulose derivatives were prepared by regioselective
      substitution of C-2, -3, and -6 position hydroxyls in cellulose by O-acetyls or
      trityls. Their dynamic structures formed in polar solvents were compared with
      those by the commercial cellulose acetates where the distribution of hydroxyls
      and O-acetyls was nearly random in the chain. It was found that the difference in
      the chain architecture induces a large difference in the chain conformation, the
      solubility, and the clustering mechanism and structures; i.e., they changed with
      solvent quality, concentration, temperature, strength of external field, and so
      on. Copyright 2000 Academic Press.

PMID- 10926468
TI  - Effect of Fiber-Polymer Interactions on Fracture Toughness Behavior of Carbon
      Fiber-Reinforced Epoxy Matrix Composites.
AB  - The effect of anodic oxidation on high-strength polyacrylonitrile-based carbon
      fibers has been studied in terms of fiber surface energetics and fracture
      toughness of the composites. According to contact angle measurements based on the
      wicking rate of a test liquid, anodic oxidation leads to an increase in surface
      free energy, mainly due to the increase of its specific (or polar) component. For
      the carbon-fiber-reinforced epoxy resin matrix system, a direct linear
      relationship is shown between the specific component and the critical stress
      intensity factor measured by the single edge notched beam fracture toughness
      test. From a surface-energetic point of view, the anodic treatment may be
      suitable for carbon fibers incorporated in a polar organic matrix, resulting in
      an increased specific component of the surface free energy. Good wetting plays an
      important role in improving the degree of adhesion at interfaces between fibers
      and matrices of the resulting composites. Copyright 2000 Academic Press.

PMID- 10926469
TI  - Permeation of Liquids through Inorganic Nanofiltration Membranes.
AB  - Inorganic nanofiltration membranes were prepared using silica-zirconia composite
      sols by the sol-gel method and applied for the permeation experiments of
      nonaqueous solutions. Pure solvent permeabilities of methanol, ethanol, and 1
      propanol were measured at temperatures from 25 to 60 degrees C. For membranes
      having pore sizes as large as 70 nm, the permeation mechanism of alcohols obeys
      the viscous flow mechanism irrespective of types of alcohols. On the other hand,
      the permeation mechanism through porous silica-zirconia membranes having pore
      diameters of 1 to 5 nm was found to be different from the viscous flow mechanism;
      small molecules showed larger permeabilities than large molecules. Activation
      energies of solvent permeability were found to be larger for large molecules and
      for membranes of smaller pore size. Copyright 2000 Academic Press.

PMID- 10926470
TI  - Adsorption of Ethyl(hydroxyethyl)cellulose onto Silica Particles: The Role of
      Surface Chemistry and Temperature.
AB  - The adsorption characteristics of an ethyl(hydroxyethyl)cellulose (EHEC) polymer
      onto colloidal silica particles from aqueous solution have been investigated. The
      influence of solution temperature and the silica surface chemistry on EHEC
      adsorption isotherms and adsorbed layer thicknesses have been determined in an
      attempt to elucidate the mechanisms of adsorption. As the hydrophobicity of the
      silica particles are increased by physical and chemical treatment, the plateau
      EHEC adsorbed amount increased, while the corresponding adsorbed layer thickness
      decreased. The estimated free energy of adsorption (DeltaG(o)(ads)) was shown to
      be dependent on the silica surface chemistry, but did not correlate directly with
      silica's advancing water contact angle and suggests that EHEC adsorption is not
      directly controlled by hydrophobicity alone. As the solution temperature
      increased from 18 to 37 degrees C, the plateau coverage of EHEC increased while
      the layer thickness generally decreased, this concurred with a reduction in the
      solvency. For hydrophilic and dehydrated silica particles, DeltaG(o)(ads)
      decreased in magnitude with increasing temperature, whereas for chemically
      treated silica, DeltaG(o)(ads) increased with temperature. These findings are
      discussed with respect to the specific interactions between EHEC segments and
      surface sites, which control the adsorption mechanisms of cellulose polymers.
      Copyright 2000 Academic Press.

PMID- 10926471
TI  - Influence of Anionic Layer Structure of Fe-Oxyhydroxides on the Structure of Cd
      Surface Complexes.
AB  - The nature of crystallographic reactive sites on the lepidocrocite (gammaFeOOH)
      surface has been determined by atomic force microscopy (AFM) and extended X-ray
      absorption fine structure (EXAFS) spectroscopy and compared to the surface
      bonding properties of goethite. To this end, the specific surface areas of
      lepidocrocite particles, and of their crystal faces, were calculated from the
      size and shape of individual particles determined by AFM, and the structure of Cd
      surface complexes was determined from Cd-Fe EXAFS distances. The combined results
      show that Cd forms solely mononuclear surface complexes, even at 100% surface
      coverage, and that hydrated Cd octahedra sorb on basal {010} and lateral {hk0},
      {h0l} faces of lepidocrocite platelets by sharing edges with surface Fe
      octahedra. The absence, or scarcity, of corner-sharing linkage between Fe and Cd
      octahedra on the surface of lepidocrocite is in contrast to goethite
      (alphaFeOOH), where this type of complex is predominant. The explanation for the
      observed difference of Cd sorption mechanism on these two polymorphs lies not in
      the shape and relative surface area of their crystallographic faces, but in their
      different bulk structures and, specifically, in the stacking mode of anion layers
      (O(2-), OH(-)) which is hexagonal in alphaFeOOH and cubic in gammaFeOOH. This
      study demonstrates that the stacking mode of anions in the sorbent solid is a key
      factor in determining the structure of surface complexes on mineral surfaces.
      Copyright 2000 Academic Press.

PMID- 10926472
TI  - Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Poly(lactide) at
      Hydrophilic Silica from Aqueous Solution.
AB  - The adsorption of a series of amphiphilic poly(ethylene oxide)-poly(DL-lactide)
      (PEO-PL) diblock copolymers at the water/silica interface was investigated by
      ellipsometry and reflectometry. For all copolymers, a much higher saturation
      adsorption is found compared to that of the PEO homopolymers, indicating the
      importance of the PL block for the adsorption. The copolymers display a
      saturation adsorption that increases with increasing hydrophobic content of the
      polymer, and decreases with increasing hydrophilic content of the polymer.
      Despite this, however, the layer thickness observed is rather similar for all
      polymers, regardless of the length and composition of the copolymers. Moreover,
      the layer thicknesses were significantly higher than what would be expected for
      the unperturbered copolymer dimensions. The initial adsorption kinetics of the
      different copolymers are comparable. The initial adsorption rate increases
      cooperatively with concentration and is slower than that expected for diffusion
      controlled adsorption. Moreover, the adsorption increases only slightly over a
      concentration the range from 20 to 50 degrees C. Furthermore, pH titrations show
      that all polymers exhibit a critical desorption pH of 8-9, which is lower than
      the corresponding value of pH 10.5 observed for the PEO homopolymer. These
      results are discussed in terms of the adsorption mechanism and the adsorbed layer
      structure and formation. Copyright 2000 Academic Press.

PMID- 10926473
TI  - Adsorption of Diblock Copolymers of Poly(ethylene oxide) and Polylactide at
      Hydrophobized Silica from Aqueous Solution.
AB  - The adsorption of a series of amphiphilic diblock copolymers of poly(ethylene
      oxide) (PEO) and poly(DL-lactide) (PL) at hydrophobized silica from aqueous
      solution was studied using time-resolved ellipsometry and reflectometry. The
      adsorbed amounts only display a weak dependence on the copolymer composition in
      both water and phosphate-buffered solution. For the short copolymers, the layer
      thickness decreases slightly with increasing length of the hydrophobic block.
      Furthermore, in comparison with the short copolymers, the layer thickness of the
      long copolymers is substantially higher. Upon degradation of the PL block, the
      adsorbed amount is found to decrease and approach that of the corresponding PEO
      homopolymer. Protein rejection studies indicate that the adsorption of fibrinogen
      is inhibited by copolymer preadsorption. The protein rejection is enhanced with
      increasing surface coverage of the preadsorbed copolymer, but largely independent
      of the length of the PL block and the PEO block. For all polymers investigated,
      essentially complete protein rejection is obtained above a critical surface
      coverage that is significantly lower than the saturation coverage of the
      copolymers. Removing the copolymer from bulk solution after preadsorption causes
      a partial desorption, resulting in reduced protein rejection. However, the
      protein rejection capacity with and without copolymer in the bulk solution is
      found to be similar at a given surface coverage. Contrary to the behavior of the
      intact copolymers, fibrinogen adsorption is found to be significant at surfaces
      pretreated with an extensively degraded copolymer and, in fact, quantitatively
      comparable to that at the hydrophobic surface in the absence of preadsorption.
      This finding, together with that of the effect of the copolymer composition on
      protein rejection, suggests that an efficient protein rejection is maintained
      until only a few L units remain in the copolymer, i.e., until nearly completed
      degradation. Copyright 2000 Academic Press.

PMID- 10926474
TI  - Dual Fluorescence of 2-(4'-N,N-dimethylaminophenyl)pyrido
AB  - The spectral characteristics of 2-(4'-N,N-dimethylaminophenyl)-pyrido[3,4
      d]imidazole (DMAPPI) have been studied in a TritonX-100 (TX-100)/n-hexanol/water
      reverse micelle in cyclohexane as a function of water (w(0)), surfactant,
      cosurfactant, pH, and trifluoroacetic acid. Under the neutral conditions, dual
      fluorescence (normal and twiste intramolecular charge transfer) is observed, even
      at w(0)=0, suggesting that the TICT state is stabilized by the hydrogen bonding
      from n-hexanol. These studies indicate that DMAPPI molecules are present near the
      interface of the water pool and the micellar phase toward the micellar side, and
      the changes observed in the spectral characteristics with change of w(0) are due
      to the formation of the reverse micelles and the alignment of cosurfactant around
      DMAPPI. Variation of pH in the range 3-10 has no effect on the spectral
      characteristics of DMAPPI, suggesting that the protons do not penetrate the
      reverse micelles, whereas the trifluoroacetic acid protonates DMAPPI to form
      monocations (MCs). At w(0)=0, MC2 and MC3 (see Scheme 1) are the MCs present both
      in the S(0) and S(1) states, whereas with an increase in w(0), the MC2 shifts
      toward MC1. Biprotonic phototautomerism is observed in MC1, which leads to the
      formation of MC2 in the S(1) state. Copyright 2000 Academic Press.

PMID- 10926475
TI  - Removal of Solid Organic Films from Rotating Disks Using Emulsion Cleaners.
AB  - Measurements have been made of the rate of removal of a solid organic film
      (phenanthrene) from the surface of a rotating disk using emulsions containing
      water, the nonionic surfactant Tween 20, and d-limonene as the organic phase. The
      results show that phenanthrene removal initially occurs by the uptake of
      phenanthrene into the emulsion drops as small aggregates. Simultaneously, the
      organic phase penetrates into the phenanthrene film, diminishing the adhesive
      force between the film and the substrate. After sufficient time, the phenanthrene
      film detaches from the rotating disk surface as a solid. This detachment
      mechanism accounts for the vast majority of the phenanthrene removal (
      approximately 90%). Initial solubilization rates were analyzed using two
      solubilization models. Both models assume that phenanthrene removal occurs via a
      mass transfer limited removal of phenanthrene-laden emulsion drops from the
      phenanthrene film surface into the bulk solution. One model treats the emulsion
      as homogeneous while the other accounts for the finite size of the emulsion
      droplets. The latter model was also used to relate the flux of organic phase
      impacting the phenanthrene film to the detachment times. Copyright 2000 Academic
      Press.

PMID- 10926476
TI  - Crystal Nucleation Rates for Particles Experiencing Short-Range Attractions:
      Applications to Proteins.
AB  - A kinetic model for the nucleation of a crystalline phase consisting of particles
      experiencing short-range attractions is developed. Of particular significance is
      the proximity of the metastable fluid/fluid phase boundary. The model
      incorporates self-consistent thermodynamics, changes in gradient diffusivity, and
      density fluctuations in the vicinity of the critical point. Density fluctuations
      associated with the spinodal of this metastable phase transition greatly enhance
      nucleation rates, suggesting that experimental conditions may be found where
      rapid nucleation and slow crystal growth can be achieved by moving the metastable
      critical point relative to the solubility boundary. Copyright 2000 Academic
      Press.

PMID- 10926477
TI  - pH-Dependent Surface-Enhanced Raman Scattering of 8-Hydroxy Quinoline Adsorbed on
      Silver Hydrosol.
AB  - Surface-enhanced Raman scattering (SERS) of 8-hydroxy quinoline (HQ) adsorbed on
      silver hydrosols are compared with the FTIR and normal Raman spectrum in the bulk
      and in solution. Definite evidence of the charge transfer interaction to the
      overall contribution in the SER enhancement has been reported. The excitation
      profile study also supports the evidence of a charge transfer interaction. The
      effect of pH variation on the SER band intensity is explained in terms of
      chemisorption of the molecule on bare and chlorinated silver surfaces. The
      apparent enhancement factor calculations of the principal Raman bands indicate
      that in the surface-adsorbed state, an HQ molecule is oriented neither flat nor
      vertical to the silver surface but is tilted. Copyright 2000 Academic Press.

PMID- 10926478
TI  - Structural Interpretations of Static Light Scattering Patterns of Fractal
      Aggregates.
AB  - A method based on static light scattering by fractal aggregates is introduced to
      extract structural information. In this study, we determine the scattered
      intensity by a fractal aggregate calculating the Structure and the Form factors
      noted, respectively, S(q) and F(q). We use the approximation of the mean field
      Mie scattering by fractal aggregates (R. Botet, P. Rannou, and M. Cabane, appl.
      opt. 36, 8791, 1997). This approximation is validated by a comparison of the
      scattering and extinction cross sections values calculated using, on the one
      hand, Mie theory with a mean optical index n) and, on the other hand, the mean
      field approximation. Scattering and extinction cross sections values differ by
      about 5%. We show that the mean environment of primary scatterers characterized
      by the optical index n(s) must be taken into account to interpret accurately the
      scattering pattern from fractal aggregates. Numerical simulations were done to
      evaluate the influence of the fractal dimension values (D(f)>2) and of the radius
      of gyration or the number of primary particles within the aggregates (N=50 to
      250) on the scatterers' mean optical contrast (n(s)/n). This last parameter plays
      a major role in determining the Form factor F(q) which corresponds to the primary
      particles' scattering. In associating the mean optical index (n) to structural
      characteristics, this work provides a theoretical framework to be used to provide
      additional structural information from the scattering pattern of a fractal
      aggregate (cf. Part II). Copyright 2000 Academic Press.

PMID- 10926479
TI  - Structural Interpretations of Static Light Scattering Patterns of Fractal
      Aggregates.
AB  - Information on the size and structure of aggregates is critical in predicting the
      formation kinetics, settling velocities, and reactivity of particle aggregates.
      For some systems, however, accessing this information may be very difficult.
      Light scattering measurements are among the most useful techniques for accessing
      such information. In the case of large primary particles forming aggregates, the
      common Rayleigh approximation is not valid. Instead, Mie scattering must be used
      and multiple scattering must be accounted for. Moreover, size polydispersity and
      structure of aggregates are combined in the scattered intensity measurements.
      This work presents an experimental validation of a new theoretical approach for
      extracting information on both aggregate structure and size when multiple
      scattering cannot be neglected. The chemically controlled aggregation of 0.8-um
      latex particles demonstrates the following: (1) Polydispersity effects prevent
      the interpretation of data to obtain structural information from the Structure
      factor S(q). (2) The calculated optical contrast decreasing during the
      aggregation can be correlated with the structural changes in the growing
      aggregates independently of size polydispersity. We have shown that a strict
      correlation can be obtained between the fractal dimension D(f) and the
      scatterers' mean optical contrast calculated at large scattering angles. (3) The
      changes in the Form factor (F(q)) due to multiple scattering when particles are
      close together yield a predicted structure that is in agreement with expected
      fractal dimension values and therefore S(q) can be described in term of both
      structure and size polydispersity. Copyright 2000 Academic Press.

PMID- 10926480
TI  - Electrofiltration of Aqueous Suspensions.
AB  - Electrofiltration of hydrosols in fixed-bed filters was studied experimentally.
      The experimental variables examined included media type, electric field strength,
      and suspension pH values. The extent of particle removal was found to improve
      with the application of the electric field, and lower pH values favor particle
      collection. The filtrate quality displayed the transient behavior of increasing
      particle concentration with time. A simple model which assumes that the filter
      coefficient decreases linearly with the extent of deposition was developed and
      found capable of predicting the observed behavior. Copyright 2000 Academic Press.

PMID- 10926481
TI  - The Molecular Spreading of Nonpolar Perfluoropolyether Films on Amorphous Carbon
      Surfaces.
AB  - The spreading mechanism of nonpolar perfluoropolyether films on carbon surfaces
      is examined in the mesoscopic regime, including both submonolayer and multilayer
      films. For the submonolayer film, adsorption-desorption is a main mechanism for
      spreading, and the surface diffusion coefficients increase as the film thickness
      increases. The driving force for the spreading in the submonolayer regime is the
      gradient of the disjoining pressure, which is described by the two-dimensional
      virial equation. For the multilayer film regime, the spreading characteristics
      are determined by the molecular weight and the disjoining pressure gradient,
      which is assumed to be purely van der Waals in nature. We adopt a partial slip
      boundary condition to analyze the multilayer film, which qualitatively explains
      the dependence of the surface diffusion coefficient on film thickness. Copyright
      2000 Academic Press.

PMID- 10926482
TI  - Novel On-Line Sedimentation Analyzer.
AB  - The design and development of a novel vibrating reed technique for on-line
      measurement of the sedimentation kinetics of two-phase dispersions is described.
      The feasibility of operation of the analyzer has been successfully verified in
      conjunction with a variety of model and industrially relevant systems. The former
      include mono- and polydisperse glass ballotini/water mixtures with solids
      particle sizes and concentration ranges of 55-200 um and 1.75-2.81% (v/v),
      respectively. Measured settling velocities are in good accord with those obtained
      from direct visual observation of suspension-clear liquid interfaces. The
      industrially relevant systems include agglomerated kaolin/water suspensions with
      solids concentrations as high as 20% (v/v) and oil/water emulsions with light
      phase concentrations in the range 30-50% (v/v). Copyright 2000 Academic Press.

PMID- 10926483
TI  - Electrical Conductivity and Dielectric Dispersion Phenomena of Concentrated
      TiO(2) Suspensions.
AB  - The complex conductivity of concentrated TiO(2) suspensions (up to 50 vol%) was
      measured over a large frequency range (1 MHz-1.8 GHz), as a function of grain
      volume content. These measurements highlight relaxation phenomena in the
      intermediate frequency range, which are associated with the dispersed powder.
      These phenomena were previously noted in O'Brien's theoretical developments. A
      quantitative data analysis was made, in terms of time constant distribution,
      using the CONTIN software, from Provencher. As a result, a complex process is
      highlighted, including two main mechanisms in different ranges of time constants.
      Particularly, we showed good agreement between the higher frequency mechanism and
      the O'Brien theory. From Dukhin's lambda ratios, which are ratios of grain
      surface to bulk electrolyte conductances, we calculated the electrolyte
      conductivity as a function of powder concentrations. At higher powder
      concentrations, these values are different from those measured with centrifuged
      liquids. Copyright 2000 Academic Press.

PMID- 10926484
TI  - Direct Quantification of Aspergillus niger Spore Adhesion in Liquid Using an
      Atomic Force Microscope.
AB  - An atomic force microscope has been used to quantify directly the adhesion
      between single Aspergillus niger spores and freshly cleaved mica surfaces. The
      measurements used "spore probes" constructed by immobilizing a single spore at
      the apex of a tipless AFM cantilever. Adhesion was quantified from force-distance
      data for the retraction of the spore from the surface. Studies in NaCl solutions
      over a range of pH and electrolyte concentration showed that the decrease of long
      range electrostatic repulsion with decreasing pH provided a contribution in
      increasing the overall adhesion, but the variation of such repulsion with ionic
      strength did not correlate with changes in the magnitude of adhesion. Specific
      interactions between appendages and protusions on the spore surface must play an
      important role in adhesion. The AFM spore probe technique provides a useful new
      method for evaluating the interactions of spores and surfaces. It has the
      potential to become a powerful asset for both fundamental studies and the
      assessment of new materials with low adhesion properties. Copyright 2000 Academic
      Press.

PMID- 10926485
TI  - A Simple Experimental Way of Measuring the Hamaker Constant A(11) of Divided
      Solids by Immersion Calorimetry in Apolar Liquids.
AB  - Recent progress in interpretation of immersion calorimetry has shown the link
      between the immersion enthalpy (Delta(imm)H) value in apolar liquid and the
      Lifshitz-van der Waals contribution to surface energy (gamma(LW)(S)) of divided
      solids. In this work we show that a simple relationship can be established
      between the Hamaker constant (A(11)) of a solid and its immersion enthalpy in a
      pure apolar solvent. The results are satisfying compared to those already
      available in the scientific literature. The main interest of this method is the
      measurement of the Hamaker constants of solids for which contact angle
      measurements are impossible to carry out and for those for which the complexity
      of the solid structure hampers the ab initio calculation. Values are given for
      some clay minerals. Copyright 2000 Academic Press.

PMID- 10926486
TI  - In Situ FTIR Studies of an Oxidation Product from Protein Adsorption at the
      Platinum Electrode.
AB  - The subtractively normalized interfacial Fourier transform infrared spectroscopy
      (SNIFTIRS) has been used to examine an oxidation product from adsorption of the
      enzyme, ribonuclease A, at the platinum electrode. At potentials of 600 mV (SCE),
      a negative going peak due to the formation of the oxidation product CO(2) was
      clearly visible with both s- and p-polarized IR beams. This gives evidence that
      adsorption of the protein occurs through the carboxylate groups of the acidic
      residues of the protein at anodic potentials with subsequent oxidation occurring
      by a decarboxylation mechanism. Copyright 2000 Academic Press.

PMID- 10926488
TI  - Liquid crystalline ordering of procollagen as a determinant of three-dimensional
      extracellular matrix architecture.
AB  - The precise molecular mechanisms that determine the three-dimensional
      architectures of tissues remain largely unknown. Within tissues rich in
      extracellular matrix, collagen fibrils are frequently arranged in a tissue
      specific manner, as in certain liquid crystals. For example, the continuous twist
      between fibrils in compact bone osteons resembles a cholesteric mesophase, while
      in tendon, the regular, planar undulation, or "crimp", is akin to a
      precholesteric mesophase. Such analogies suggest that liquid crystalline
      organisation plays a role in the determination of tissue form, but it is hard to
      see how insoluble fibrils could spontaneously and specifically rearrange in this
      way. Collagen molecules, in dilute acid solution, are known to form nematic,
      precholesteric and cholesteric phases, but the relevance to physiological
      assembly mechanisms is unclear. In vivo, fibrillar collagens are synthesised in
      soluble precursor form, procollagens, with terminal propeptide extensions. Here,
      we show, by polarized light microscopy of highly concentrated (5-30 mg/ml)
      viscous drops, that procollagen molecules in physiological buffer conditions can
      also develop long-range nematic and precholesteric liquid crystalline ordering
      extending over 100 microm(2) domains, while remaining in true solution. These
      observations suggest the novel concept that supra-fibrillar tissue architecture
      is determined by the ability of soluble precursor molecules to form liquid
      crystalline arrays, prior to fibril assembly.

PMID- 10926487
TI  - Characterisation of the newly identified human Ump1 homologue POMP and analysis
      of LMP7(beta 5i) incorporation into 20 S proteasomes.
AB  - Biogenesis of mammalian 20 S proteasomes occurs via precursor complexes
      containing alpha and unprocessed beta subunits. A human homologue of the yeast
      proteasome maturation factor Ump1 was identified in 2D gels of 16 S precursor
      preparations and designated as POMP (proteasome maturation protein). We show that
      POMP is detected only in precursor fractions and not in fractions containing
      mature 20 S proteasome. Northern blot experiments revealed that expression of
      POMP is induced after treatment with interferon gamma. To analyse the role of the
      beta 5 propeptide for proper maturation and incorporation of the beta 5 subunit
      into the complex, human T2 cells, which highly express derivatives of the beta 5i
      subunit (LMP7), were studied. In contrast to yeast, the presence of the beta 5
      propeptide is not essential for incorporation of LMP7 into the proteasome
      complex. Mutated LMP7 subunits either carrying the prosequence of beta 2i (LMP2)
      or containing a mutation in the active threonine site are incorporated like wild
      type LMP7, while a LMP7 derivative lacking the prosequence completely is
      incorporated to a lesser extent. Although the absence of the prosequence does not
      affect incorporation of LMP7, its deletion leads to delayed proteasome maturation
      and thereby to an accumulation of precursor complexes. As a result of the
      precursor accumulation, an increased amount of the POMP protein can be detected
      in these cells.

PMID- 10926489
TI  - Crystal structure of the beta-apical domain of the thermosome reveals structural
      plasticity in the protrusion region.
AB  - The crystal structure of the beta-apical domain of the thermosome, an archaeal
      group II chaperonin from Thermoplasma acidophilum, has been determined at 2.8 A
      resolution. The structure shows an invariant globular core from which a 25 A long
      protrusion emanates, composed of an elongated alpha-helix (H10) and a long
      extended stretch consisting of residues GluB245-ThrB253. A comparison with
      previous apical domain structures reveals a large segmental displacement of the
      protruding part of helix H10 via the hinge GluB276-ValB278. The region comprising
      residues GluB245-ThrB253 adopts an extended beta-like conformation rather than
      the alpha-helix seen in the alpha-apical domain. Consequently, it appears that
      the protrusions of the apical domains from group II chaperonins might assume a
      variety of context-dependent conformations during an open, substrate-accepting
      state of the chaperonin. Sequence variations in the protrusion regions that are
      found in the eukaryotic TRiC/CCT subunits may provide different structural
      propensities and hence serve different roles in substrate recognition.

PMID- 10926490
TI  - Prediction of transcription terminators in bacterial genomes.
AB  - This study describes an algorithm that finds rho-independent transcription
      terminators in bacterial genomes and evaluates the accuracy of its predictions.
      The algorithm identifies terminators by searching for a common mRNA motif: a
      hairpin structure followed by a short uracil-rich region. For each terminator, an
      energy-scoring function that reflects hairpin stability, and a tail-scoring
      function based on the number of U nucleotides and their proximity to the stem,
      are computed. A confidence value can be assigned to each terminator by analyzing
      candidate terminators found both within and between genes, and taking into
      account the energy and tail scores. The confidence is an empirical estimate of
      the probability that the sequence is a true terminator. The algorithm was used to
      conduct a comprehensive analysis of 12 bacterial genomes to identify likely
      candidates for rho-independent transcription terminators. Four of these genomes
      (Deinococcus radiodurans, Escherichia coli, Haemophilus influenzae and Vibrio
      cholerae) were found to have large numbers of rho-independent terminators. Among
      the other genomes, most appear to have no transcription terminators of this type,
      with the exception of Thermotoga maritima. A set of 131 experimentally determined
      E. coli terminators was used to evaluate the sensitivity of the method, which
      ranges from 89 % to 98 %, with corresponding false positive rates of 2 % and 18
      %.

PMID- 10926491
TI  - The internal head protein Gp16 controls DNA ejection from the bacteriophage T7
      virion.
AB  - A wild-type T7 virion ejects about 850 bp of the 40 kb genome into the bacterial
      cell by a transcription-independent process. Internalization of the remainder of
      the genome normally requires transcription. Inhibition of transcription
      independent DNA translocation beyond the leading 850 bp is not absolute but the
      time taken by a population of phage genomes in overcoming the block averages
      about 20 minutes at 30 degrees C. There are additional blocks to transcription
      independent translocation and less than 20 % of infecting DNA molecules
      completely penetrate the cell cytoplasm after four hours of infection. Mutant
      virions containing an altered gene 16 protein either prevent the blocks to
      transcription-independent DNA translocation or effect rapid release from blocking
      sites and allow the entire phage DNA molecule to enter the cell at a constant
      rate of about 75 bp per second. This rate is likely the same at which the leading
      850 bp is ejected into the cell from a wild-type virion. All mutations fall into
      two clusters contained within 380 bp of the 4 kb gene 16, suggesting that a 127
      residue segment of gp16 controls DNA ejection from the phage particle. We suggest
      that this segment of gp16 acts as a clamp to prevent transcription-independent
      DNA translocation.

PMID- 10926492
TI  - The role of the central zinc fingers of transcription factor IIIA in binding to 5
      S RNA.
AB  - In the nine-zinc finger Xenopus transcription factor TFIIIA the central group of
      fingers, fingers 4 to 7, have been shown to bind to 5 S RNA. In this study, we
      have attempted to assess the role of this region of the TFIIIA molecule in more
      detail than hitherto. High-resolution footprinting by RNases A and CV1 has been
      used to probe the binding to 5 S RNA of three TFIIIA peptides Tf(1-6), Tf(4-6)
      and Tf(4-7), consisting of fingers 1 to 6, 4 to 6, and 4 to 7, respectively, and
      of full-length TFIIIA. The results pinpoint the outer margins of binding of the
      central fingers within helices IV and II of TFIIIA. A comparison of the
      footprints reveals that the presence of finger 7 affords protection at positions
      C19 and U55, the distal portion of helix II and the proximal portion of loop B.
      In addition, our footprints suggest that the central fingers bind in the same
      manner, whether in an isolated group or in the intact TFIIIA molecule. In a
      companion study, we have determined the binding affinities of Tf(4-6) and Tf(4-7)
      for full-length and three truncated 5 S RNA molecules, the latter selected on the
      basis of the regions of the 5 S RNA molecule known to be important in the binding
      of TFIIIA. The analysis uses only fully active protein involved in the binding
      and the results are consistent with the corresponding footprinting results. This
      is the first time that a detailed study of the binding site of one particular
      zinc finger to RNA has been reported; the results should be of use in the design
      of 5 S RNA molecules and TFIIIA peptides for structural studies of the
      interaction between zinc fingers and RNA.

PMID- 10926493
TI  - Biochemical characterization of a clamp-loader complex homologous to eukaryotic
      replication factor C from the hyperthermophilic archaeon Sulfolobus solfataricus.
AB  - Here we report the isolation and characterization of a clamp-loader complex from
      the thermoacidophilic archaeon Sulfolobus solfataricus (SsoRFC). SsoRFC is a
      hetero-pentamer composed of polypeptides of 37 kDa (small subunit) and 46 kDa
      (large subunit), which possess primary structure similarity with human
      replication factor C p40 and p140 subunits, respectively. The two SsoRFC
      polypeptides were co-expressed in Escherichia coli and purified as a complex
      (SsoRFC-complex) that was demonstrated to possess a native M(r) of about 200 kDa
      and a 4:1 (small to large) subunit stoichiometric ratio. The small subunit was
      individually expressed in E. coli, purified, and found to form a homo-tetramer
      (SsoRFC-small; native M(r) 156 kDa), which was also characterized. The SsoRFC
      complex, but not SsoRFC-small, highly stimulated the synthetic activity of S.
      solfataricus B1-type DNA polymerase in reactions containing primed M13mp18 DNA,
      ATP, and either of the two poliferating cell nuclear antigen-like processivity
      factors of S. solfataricus (039p and 048p). Both SsoRFC-small and -complex were
      able to hydrolyze ATP, but only the ATPase activity of the holo-enzymatic
      assembly was activated by primed DNA templates, such as poly(dA)-oligo(dT). As
      measured by nitrocellulose filter binding assays, SsoRFC-complex bound poly(dA)
      oligo(dT), but not the unprimed homopolymer, whereas SsoRFC-small was devoid of
      any DNA-binding activity. The peculiar properties of this archaeal clamp-loader
      complex and their significance for the understanding of the DNA replication
      process in Archaea are discussed.

PMID- 10926494
TI  - Microbial genome analyses: comparative transport capabilities in eighteen
      prokaryotes.
AB  - Here, we present a comprehensive analysis of solute transport systems encoded
      within the completely sequenced genomes of 18 prokaryotic organisms. These
      organisms include four Gram-positive bacteria, seven Gram-negative bacteria, two
      spirochetes, one cyanobacterium and four archaea. Membrane proteins are analyzed
      in terms of putative membrane topology, and the recognized transport systems are
      classified into 76 families, including four families of channel proteins, four
      families of primary carriers, 54 families of secondary carriers, six families of
      group translocators, and eight unclassified families. These families are analyzed
      in terms of the paralogous and orthologous relationships of their protein
      members, the substrate specificities of their constituent transporters and their
      distributions in each of the 18 organisms studied. The families vary from large
      superfamilies with hundreds of represented members, to small families with only
      one or a few members. The mode of transport generally correlates with the primary
      mechanism of energy generation, and the numbers of secondary transporters
      relative to primary transporters are roughly proportional to the total numbers of
      primary H(+) and Na(+) pumps in the cell. The phosphotransferase system is less
      prevalent in the analyzed bacteria than previously thought (only six of 14
      bacteria transport sugars via this system) and is completely lacking in archaea
      and eukaryotes. Escherichia coli is shown to be exceptionally broad in its
      transport capabilities and therefore, at a membrane transport level, does not
      appear representative of the bacteria thus far sequenced. Archaea and spirochetes
      exhibit fewer proteins with multiple transmembrane segments and fewer net
      transporters than most bacteria. These results provide insight into the relevance
      of transport to the overall physiology of prokaryotes.

PMID- 10926495
TI  - Selection of peptidic mimics of digoxin from phage-displayed peptide libraries by
      anti-digoxin antibodies.
AB  - Since the initial report of the development of methodology to generate high
      affinity digitalis-specific (digoxin) antibodies, these antibodies have proven
      extremely useful tools to monitor digoxin levels in digitalized patients and, as
      Fab fragments, to reverse toxic digoxin effects in life-threatening digoxin
      overdoses. These antibodies (both digoxin-specific and ouabain-specific) have
      been used extensively by investigators for the identification and
      characterization of putative endogenous digitalis-like factors. In this study, we
      used two well-characterized mouse anti-digoxin monoclonal antibodies (mAbs),
      designated 26-10 and 45-20, as binding templates with which to select short
      bacteriophage-displayed (pIII protein inserted) peptides that are capable of
      binding to these mAbs and mimicking the conformational structure of digoxin.
      Selective enrichment from two phage-displayed random peptide libraries enabled us
      to isolate and identify distinct 15 and 26 amino acid residue peptide inserts
      that bind with high avidity and idiotypic specificity to the selecting mAbs.
      Among these displayed inserts a subset was identified whose mAb binding is
      inhibited by digoxin and whose corresponding synthetic peptides inhibit phage
      binding. They, therefore, appear to bind at the mAbs digoxin-binding sites. These
      data provide the first clear evidence that short polypeptides can serve as
      surrogates for the low molecular mass hapten digoxin.

PMID- 10926496
TI  - 2.8 A crystal structure of the malachite green aptamer.
AB  - Previous in vitro selection experiments identified an RNA aptamer that recognizes
      the chromophore malachite green (MG) with a high level of affinity, and which
      undergoes site-specific cleavage following laser irradiation. To understand the
      mechanism by which this RNA folds to recognize specifically its ligand and the
      structural basis for chromophore-assisted laser inactivation, we have determined
      the 2.8 A crystal structure of the aptamer bound to tetramethylrosamine (TMR), a
      high-affinity MG analog. The ligand-binding site is defined by an asymmetric
      internal loop, flanked by a pair of helices. A U-turn and several non-canonical
      base interactions stabilize the folding of loop nucleotides around the TMR. The
      aptamer utilizes several tiers of stacked nucleotides arranged in pairs, triples,
      and a novel base quadruple to effectively encapsulate the ligand. Even in the
      absence of specific stabilizing hydrogen bonds, discrimination between related
      fluorophores and chromophores is possible due to tight packing in the RNA binding
      pocket, which severely limits the size and shape of recognized ligands. The site
      of laser-induced cleavage lies relatively far from the bound TMR ( approximately
      15 A). The unusual backbone conformation of the cleavage site nucleotide and its
      high level of solvent accessibility may combine to allow preferential reaction
      with freely diffusing hydroxyl radicals generated at the bound ligand. Several
      observations, however, favor alternative mechanisms for cleavage, such as
      conformational changes in the aptamer or long-range electron transfer between the
      bound ligand and the cleavage site nucleotide.

PMID- 10926497
TI  - A two-stranded template-based approach to G.(C-A) triad formation: designing
      novel structural elements into an existing DNA framework.
AB  - We have designed a DNA sequence, d(G-G-G-T-T-C-A-G-G), which dimerizes to form a
      2-fold symmetric G-quadruplex in which G(syn). G(anti).G(syn).G(anti) tetrads are
      sandwiched between all trans G. (C-A) triads. The NMR-based solution structural
      analysis was greatly aided by monitoring hydrogen bond alignments across N-H...N
      and N-H...O==C hydrogen bonds within the triad and tetrad, in a uniformly
      ((13)C,(15)N)-labeled sample of the d(G-G-G-T-T-C-A-G-G) sequence. The solution
      structure establishes that the guanine base-pairs with the cytosine through
      Watson-Crick G.C pair formation and with adenine through sheared G.A mismatch
      formation within the G.(C-A) triad. A model of triad DNA was constructed that
      contains the experimentally determined G.(C-A) triad alignment as the repeating
      stacked unit.

PMID- 10926498
TI  - Crystal structure of the amino-terminal coiled-coil domain of the APC tumor
      suppressor.
AB  - Coiled coils serve as dimerization domains for a wide variety of proteins,
      including the medically important oligomeric tumor suppressor protein, APC.
      Mutations in the APC gene are associated with an inherited susceptibility to
      colon cancer and with approximately 75 % of sporadic colorectal tumors. To define
      the basis for APC pairing and to explore the anatomy of dimeric coiled coils, we
      determined the 2.4 A resolution X-ray crystal structure of the N-terminal
      dimerization domain of APC. The peptide APC-55, encompassing the heptad repeats
      in APC residues 2-55, primarily forms an alpha-helical, coiled-coil dimer with
      newly observed core packing features. Correlated asymmetric packing of four core
      residues in distinct, standard rotamers is associated with a small shift in the
      helix register. At the C terminus, the helices splay apart and interact with a
      symmetry-related dimer in the crystal to form a short, anti-parallel, four-helix
      bundle. N-terminal fraying and C-terminal splaying of the helices, as well as the
      asymmetry and helix register shift describe unprecedented dynamic excursions of
      coiled coils. The low stability of APC-55 and divergence from the expected coiled
      coil fold support the suggestion that the APC dimerization domain may extend
      beyond the first 55 residues.

PMID- 10926499
TI  - Crystallographic and energetic analysis of binding of selected anions to the
      yellow variants of green fluorescent protein.
AB  - The fluorescence emission of yellow fluorescent proteins (YFPs) has been shown to
      respond rapidly and reversibly to changes in the concentration of some small
      anions such as halides; this allows for the use of YFPs as genetically encodable
      Cl(-) sensors that may be targeted to specific organelles in living cells.
      Fluorescence is suppressed due to protonation of the chromophore upon anion
      binding, with a stronger level of interaction at low pH values. At pH 6.0, the
      apparent dissociation constant (K(app)) for Cl(-) is 32 mM for YFP and 22 mM for
      YFP-H148Q, whereas at pH 7.5, K(app) is 777 mM and 154 mM, respectively. In the
      cytosol, YFP-H148Q appears most promising as a halide sensor due to its high
      degree of sensitivity towards I(-) (K(app)=23 mM at pH 7.5). To aid in the design
      of variants with improved levels of specificity and affinity for Cl(-), we solved
      apo and I(-)-bound crystal structures of YFP-H148Q to 2.1 A resolution. The
      halide-binding site is found near van der Waals contact with the chromophore
      imidazolinone oxygen atom, in a small buried cavity adjacent to Arg96, which
      provides electrostatic stabilization. The halide ion is hydrogen bonded to the
      phenol group of T203Y, consistent with a mutational analysis that indicates that
      T203Y is indispensible for tight binding. A series of conformational changes
      occurs in the amphiphilic site upon anion binding, which appear to be propagated
      to the beta-bulge region around residue 148 on the protein surface. Anion binding
      raises the chromophore pK(a) values, since delocalization of the phenolate
      negative charge over the chromophore skeleton is suppressed. Extraction of
      microscopic binding constants for the linked equilibrium between anion and proton
      binding indicates that anion selectivity by YFP is related to hydration forces.
      Specific suggestions to improve Cl(-) binding to YFP-H148Q based on size and
      hydration energy are proposed.

PMID- 10926500
TI  - HMMSTR: a hidden Markov model for local sequence-structure correlations in
      proteins.
AB  - We describe a hidden Markov model, HMMSTR, for general protein sequence based on
      the I-sites library of sequence-structure motifs. Unlike the linear hidden Markov
      models used to model individual protein families, HMMSTR has a highly branched
      topology and captures recurrent local features of protein sequences and
      structures that transcend protein family boundaries. The model extends the I
      sites library by describing the adjacencies of different sequence-structure
      motifs as observed in the protein database and, by representing overlapping
      motifs in a much more compact form, achieves a great reduction in parameters. The
      HMM attributes a considerably higher probability to coding sequence than does an
      equivalent dipeptide model, predicts secondary structure with an accuracy of 74.3
      %, backbone torsion angles better than any previously reported method and the
      structural context of beta strands and turns with an accuracy that should be
      useful for tertiary structure prediction.

PMID- 10926501
TI  - Formation of cytoplasmic turns between two closely spaced transmembrane helices
      during membrane protein integration into the ER membrane.
AB  - The helical hairpin, two closely spaced transmembrane helices separated by a
      short turn, is a recurring structural element in integral membrane proteins, and
      may serve as a compact unit that inserts into the membrane en bloc. Previously,
      we have determined the propensities of the 20 natural amino acids, when present
      in the middle of a long hydrophobic stretch, to induce the formation of a helical
      hairpin with a lumenally exposed turn during membrane protein assembly into the
      endoplasmic reticulum membrane. Here, we present results from a similar set of
      measurements, but with the turn placed on the cytoplasmic side of the membrane.
      We find that a significantly higher number of turn-promoting residues need to be
      present to induce a cytoplasmic turn compared to a lumenal turn, and that, in
      contrast to the lumenal turn, the positively charged residues Arg and Lys are the
      strongest turn-promoters in cytoplasmic turns. These results suggest that the
      process of turn formation between transmembrane helices is different for lumenal
      and cytoplasmic turns.

PMID- 10926502
TI  - Sequence conservation provides the best prediction of the role of proline
      residues in p13suc1.
AB  - The unique nature of the proline side-chain imposes severe constraints on the
      polypeptide backbone, and thus it seems likely that it plays a special structural
      or functional role in the architecture of proteins. We have investigated the role
      of proline residues in suc1, a member of the cyclin-dependent kinase (cks) family
      of proteins, whose known function is to bind to and regulate the activity of the
      major mitotic cdk. The effect on stability of mutation to alanine of all but two
      of the eight proline residues is correlated with their conservation within the
      family. The remaining two proline residues are located in the hinge loop between
      two beta-strands that mediates a domain-swapping process involving exchange of a
      beta-strand between two monomers to form a dimer pair. Mutation of these proline
      residues to alanine stabilises the protein. cdk binding is unaffected by these
      mutations, but dimerisation is altered. We propose, therefore, that the double
      proline motif is conserved for the purpose of domain swapping, which suggests
      that this phenomenon plays a role in the function of cks proteins. Thus, the
      conservation of the proline residues is a good indicator of their roles in suc1,
      either in the stabilisation of the native state or in performing functions that
      are as yet unknown. In addition, the strain resulting from two of the proline
      residues was relieved successfully by mutation of the preceeding residue to
      glycine, suggesting a general method for designing more stable proteins.

PMID- 10926503
TI  - Substitutions at the P(1) position in BPTI strongly affect the association energy
      with serine proteinases.
AB  - The role of the S(1) subsite in trypsin, chymotrypsin and plasmin has been
      examined by measuring the association with seven different mutants of bovine
      pancreatic trypsin inhibitor (BPTI); the mutants contain Gly, Ala, Ser, Val, Leu,
      Arg, and Trp at the P(1) position of the reactive site. The effects of
      substitutions at the P(1) position on the association constants are very large,
      comprising seven orders of magnitude for trypsin and plasmin, and over five
      orders for chymotrypsin. All mutants showed a decrease of the association
      constant to the three proteinases in the same order: Ala>Gly>Ser>Arg>Val>Leu>Trp.
      Calorimetric and circular dichroism methods showed that none of the P1
      substitutions, except the P1-Val mutant, lead to destabilisation of the binding
      loop conformation. The X-ray structure of the complex formed between bovine beta
      trypsin and P(1)-Leu BPTI showed that the P(1)-Leu sterically conflicts with the
      side-chain of P(3)-Ile, which thereby is forced to rotate approximately 90
      degrees. Ile18 (P(3)) in its new orientation, in turn interacts with the Tyr39
      side-chain of trypsin. Introduction of a large side-chain at the P1' position
      apparently leads to a cascade of small alterations of the trypsin-BPTI interface
      that seem to destabilise the complex by it adopting a less optimized packing and
      by tilting the BPTI molecule up to 15 degrees compared to the native trypsin-BPTI
      complex.

PMID- 10926504
TI  - On the role of the N-terminal group in the allosteric function of glucosamine-6
      phosphate deaminase from Escherichia coli.
AB  - Glucosamine-6-phosphate deaminase (EC 3.5.99.6) from Escherichia coli is an
      allosteric enzyme of the K-type, activated by N-acetylglucosamine 6-phosphate. It
      is a homohexamer and has six allosteric sites located in clefts between the
      subunits. The amino acid side-chains in the allosteric site involved in phosphate
      binding are Arg158, Lys160 and Ser151 from one subunit and the N-terminal amino
      group from the facing polypeptide chain. To study the functional role of the
      terminal amino group, we utilized a specific non-enzymic transamination reaction,
      and we further reduced the product with borohydride, to obtain the corresponding
      enzyme with a terminal hydroxy group. Several experimental controls were
      performed to assess the procedure, including reconditioning of the enzyme samples
      by refolding chromatography. Allosteric activation by N-acetylglucosamine 6
      phosphate became of the K-V mixed type in the transaminated protein. Its kinetic
      study suggests that the allosteric equilibrium for this modified enzyme is
      displaced to the R state, with the consequent loss of co-operativity. The
      deaminase with a terminal hydroxy acid, obtained by reducing the transaminated
      enzyme, showed significant recovery of the catalytic activity and its allosteric
      activation pattern became similar to that found for the unmodified enzyme. It had
      lost, however, the pH-dependence of homotropic co-operativity shown by the
      unmodified deaminase in the pH range 6-8. These results show that the terminal
      amino group plays a part in the co-operativity of the enzyme and, more
      importantly, indicate that the loss of this co- operativity at low pH is due to
      the hydronation of this amino group.

PMID- 10926505
TI  - 3-Deoxy-D-manno-octulosonate-8-phosphate synthase from Escherichia coli. Model of
      binding of phosphoenolpyruvate and D-arabinose-5-phosphate.
AB  - The crystal structure of 3-deoxy-d-manno-octulosonate-8-phosphate synthase
      (KDOPS) from Escherichia coli was determined by molecular replacement using
      coordinates given to us by Radaev and co-workers prior to publication. The KDOPS
      crystals reported by Radaev et al. were grown in the presence of 1.4 M
      (NH(4))(2)SO(4) and 0.4 M (K/H)(3)PO(4). They are in the cubic space group I23
      (a=228.6 A) with a tetramer in the asymmetric unit; the structure has been
      refined with data to 2.4 A. Our crystals of E. coli KDOPS, grown in 24 % (w/v)
      polyethylene glycol (PEG) 1500 in the presence of the substrates, 2
      phosphoenolpyruvate (PEP) and d-arabinose-5-phosphate (A5P), are also in space
      group I23 (a=118.2 A), with one subunit in the asymmetric unit. The medium of
      crystallization, 1.8 M SO(4)/PO(4) versus 24 % PEG, does not significantly affect
      the conformation of KDOPS. The inter-monomer contacts in both structures are the
      same. The beta(8)/alpha(8) loop (residues 246 to 251) situated near the entrance
      to the active site is not seen in the 229 A structure but can be traced in the
      118 A structure. Most significantly, Radaev et al. interpreted two SO(4)/PO(4)
      sites in the 229 A structure as marking the phosphate positions of the
      substrates, PEP and A5P, after the precedent of DAHPS. In the 118 A structure the
      inner of these two SO(4)/PO(4) peaks is present at the same position as in the
      229 A structure of KDOPS. The outer phosphate peak in the 118 A KDOPS is 3.7 A
      from the outer SO(4)/PO(4) peak in the 229 A structure and is within hydrogen
      bonding distance of Arg63 of the same subunit and Arg120 of another subunit.
      Based on the precedent of the d-erythrose-4-phosphate (E4P) modeled in the active
      site of DAHPS, we have modeled PEP and A5P in KDOPS and compared the coordination
      of PEP and A5P in KDOPS with that of PEP and E4P in DAHPS.

PMID- 10926507
TI  - Ensemble modulation as an origin of denaturant-independent hydrogen exchange in
      proteins.
AB  - Native state hydrogen exchange (HX) has become a powerful tool for the analysis
      of conformational states that exist under native conditions. However, the
      interpretation of HX data in terms of conformational fluctuations is still
      controversial. In particular, it has been shown that many residues display
      exchange behavior that is independent of denaturant concentration. It has been
      postulated that this lack of denaturant dependence results from local
      fluctuations that do not expose appreciable amounts of buried surface area. Here,
      we use a general thermodynamic description of HX to explore the different
      possibilities for this behavior. We find that the denaturant dependence seen in
      HX experiments under native conditions is not a de facto indication of the amount
      of surface area exposure required for exchange. Instead, this behavior results
      from the relatively homogenous character of the conformational ensemble that
      exists under native conditions and the non-specific nature of denaturant effects.
      Furthermore, a comparison of the HX behavior from a stabilized mutant of
      Staphylococcal nuclease (SNase) with that predicted for the wild-type SNase from
      the COREX algorithm suggests that denaturant-independent exchange of many
      residues is consistent with significant (approximately 10 %) surface area
      exposure for this protein.

PMID- 10926506
TI  - Crystal structure of a phage library-derived single-chain Fv fragment complexed
      with turkey egg-white lysozyme at 2.0 A resolution.
AB  - The three-dimensional structure of the single-chain Fv fragment 1F9 in complex
      with turkey egg-white lysozyme (TEL) has been determined to a nominal resolution
      of 2.0 A by X-ray diffraction. The scFv fragment 1F9 was derived from phage
      display libraries in two steps and binds both hen and turkey egg-white lysozyme,
      although the level of binding affinity is two orders of magnitude greater for the
      turkey lysozyme. The comparison of the crystal structure with a model of the
      single-chain Fv fragment 1F9 in complex with hen egg-white lysozyme (HEL) reveals
      that in the latter a clash between Asp101 in lysozyme and Trp98 of the
      complementarity determining region H3 of the heavy chain variable domain occurs.
      This is the only explanation apparent from the crystal structure for the better
      binding of TEL compared to HEL. The binding site topology on the paratope is not
      simply a planar surface as is usually found in antibody-protein interfaces, but
      includes a cleft between the light chain variable domain and heavy chain variable
      domain large enough to accommodate a loop from the lysozyme. The scFv fragment
      1F9 recognizes an epitope on TEL that differs from the three antigenic
      determinants recognized in other known crystal structures of monoclonal
      antibodies in complex with lysozyme.

PMID- 10926508
TI  - Enhanced cleavage of RNA mediated by an interaction between substrates and the
      arginine-rich domain of E. coli ribonuclease E.
AB  - Endonucleolytic cutting by the essential Escherichia coli ribonuclease RNaseE has
      a central role in both the processing and decay of RNA. Previously, it has been
      shown that an oligoribonucleotide corresponding in sequence to the single
      stranded region at the 5' end of RNAI, the antisense regulator of ColE1-type
      plasmid replication, is efficiently cut by RNaseE. Combined with the knowledge
      that alteration of the structure of stem-loops within complex RNaseE substrates
      can either increase or decrease the rate of cleavage, this result has led to the
      notion that stem-loops do not serve as essential recognition motifs for RNaseE,
      but can affect the rate of cleavage indirectly by, for example, determining the
      single-strandedness of the site or its accessibility. We report here, however,
      that not all oligoribonucleotides corresponding to RNaseE-cleaved segments of
      complex substrates are sufficient to direct efficient RNaseE cleavage. We provide
      evidence using 9 S RNA, a precursor of 5 S rRNA, that binding of structured
      regions by the arginine-rich RNA- binding domain (ARRBD) of RNaseE can be
      required for efficient cleavage. Binding by the ARRBD appears to counteract the
      inhibitory effects of sub-optimal cleavage site sequence and overall substrate
      conformation. Furthermore, combined with the results from recent analyses of E.
      coli mutants in which the ARRBD of RNase E is deleted, our findings suggest that
      substrate binding by RNaseE is essential for the normal rapid decay of E. coli
      mRNA. The simplest interpretation of our results is that the ARRBD recruits
      RNaseE to structured RNAs, thereby increasing the localised concentration of the
      N-terminal catalytic domain, which in turn leads to an increase in the rate of
      cleavage.

PMID- 10926510
TI  - The 3'-tail of a forked-duplex sterically determines whether one or two DNA
      strands pass through the central channel of a replication-fork helicase.
AB  - DnaB helicase is a ring-shaped hexamer that unwinds DNA at a replication fork. To
      understand how this protein interacts with DNA during unwinding, DnaB from
      Thermus aquaticus was incubated with chemically modified forked-duplex DNA
      substrates and the unwinding rates were measured. Unwinding was inhibited by
      modifications made to the 5'-tail, but not the 3'-tail, suggesting that the
      helicase interacts with the 5'-tail but not the 3'-tail during unwinding. Using
      oligonucleotides of mixed polarity, it was confirmed that DnaB translocates in
      the 5' to 3' direction as it unwinds DNA. A substrate was synthesized that
      contained two duplexes in tandem. Experiments involving various modifications of
      this tandem duplex demonstrated that when the 3'-tail is short, two stands of DNA
      pass through the central channel of DnaB with no resultant unwinding. Thus, the
      role of the 3'-tail in stimulating unwinding has been elucidated. The 3'-tail
      does not bind to DnaB during unwinding, but sterically determines whether one or
      two DNA strands pass through the central channel of DnaB. Furthermore, a new
      substrate for DnaB locomotion has been discovered. DnaB may actively translocate
      in the 5' to 3' direction along single-stranded DNA, even when a complementary
      strand is also present within the protein's central channel. This new mode of
      action may regulate DnaB activity by inhibiting unwinding at regions of DNA that
      are not forked. Furthermore, this new function for DnaB may coordinate abortion
      of leading and lagging strand replication if a nick is encountered on the leading
      strand.

PMID- 10926509
TI  - Function of tyrosyl-tRNA synthetase in splicing group I introns: an induced-fit
      model for binding to the P4-P6 domain based on analysis of mutations at the
      junction of the P4-P6 stacked helices.
AB  - We used an Escherichia coli genetic assay based on the phage T4 td intron to test
      the ability of the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (CYT
      18 protein) to suppress mutations that cause structural defects around its
      binding site in the P4-P6 domain of the group I intron catalytic core. We
      analyzed all possible combinations of nucleotides at either P4 bp-1 or P6 bp-1,
      which together form the junction of the P4-P6 stacked helices, and looked for
      synergistic effects in double mutants. Most mutations at either position inhibit
      self-splicing, but can be suppressed by CYT-18. CYT-18 can compensate efficiently
      for mutations that disrupt base-pairing at either P4 bp-1 or P6 bp-1, for
      mutations at P6 bp-1 that disrupt the base-triple interaction with J3/4-3, and
      for nucleotide substitutions at either position that are predicted to be
      suboptimal for base stacking, based on the analysis of DNA four-way junctions.
      However, CYT-18 has difficulty suppressing combinations of mutations at P4 bp-1
      and P6 bp-1 that simultaneously disrupt base-pairing and base stacking. Thermal
      denaturation and Fe(II)-EDTA analysis showed that mutations at the junction of
      the P4-P6 stacked helices lead to grossly impaired tertiary-structure formation
      centered in the P4-P6 domain. CYT-18-suppressible mutants bind the protein with
      K(d) values up to 79-fold higher than that for the wild-type intron, but in all
      cases tested, the k(off) value for the complex remains within twofold of the wild
      type value, suggesting that the binding site can be formed properly and that the
      increased K(d) value reflects primarily an increased k(on) value for the binding
      of CYT-18 to the misfolded intron. Our results indicate that the P4/P6 junction
      is a linchpin region, where even small nucleotide substitutions grossly disrupt
      the catalytically-active group I intron tertiary structure, and that CYT-18
      binding induces the formation of the correct structure in this region, leading to
      folding of the group I intron catalytic core.

PMID- 10926511
TI  - A comparison of the yeast and rabbit 80 S ribosome reveals the topology of the
      nascent chain exit tunnel, inter-subunit bridges and mammalian rRNA expansion
      segments.
AB  - Protein synthesis in eukaryotes is mediated by both cytoplasmic and membrane
      bound ribosomes. During the co-translational translocation of secretory and
      membrane proteins, eukaryotic ribosomes dock with the protein conducting channel
      of the endoplasmic reticulum. An understanding of these processes will require
      the detailed structure of a eukaryotic ribosome. To this end, we have compared
      the three-dimensional structures of yeast and rabbit ribosomes at 24 A
      resolution. In general, we find that the active sites for protein synthesis and
      translocation have been highly conserved. It is interesting that a channel was
      visualized in the neck of the small subunit whose entrance is formed by a deep
      groove. By analogy with the prokaryotic small subunit, this channel may provide a
      conserved portal through which mRNA is threaded into the decoding center. In
      addition, both the small and large subunits are built around a dense tubular
      network. Our analysis further suggests that the nascent chain exit tunnel and the
      docking surface for the endoplasmic reticulum channel are formed by this network.
      We surmise that many of these features correspond to rRNA, based on biochemical
      and structural data. Ribosomal function is critically dependent on the specific
      association of small and large subunits. Our analysis of eukaryotic ribosomes
      reveals four conserved inter-subunit bridges with a geometry similar to that
      found in prokaryotes. In particular, a double-bridge connects the small subunit
      platform with the interface canyon on the large subunit. Moreover, a novel bridge
      is formed between the platform and the base of the L1 domain. Finally, size
      differences between mammalian and yeast large subunit rRNAs have been correlated
      with five expansion segments that form two large spines and three extended
      fingers. Overall, we find that expansion segments within the large subunit rRNA
      have been incorporated at positions distinct from the active sites for protein
      synthesis and translocation.

PMID- 10926512
TI  - Domain rotations between open, closed and bullet-shaped forms of the thermosome,
      an archaeal chaperonin.
AB  - Three conformations of the thermosome, an archaeal group II chaperonin, have been
      determined by cryo-electron microscopy (EM). We describe an open form of the
      double-ring oligomer, a closed form and a bullet-shaped form with one ring open
      and the other closed. Domain movements have been deduced by docking atomic
      coordinates into the EM maps. The subunit apical domains, bearing the putative
      substrate binding sites, rotate about 30 degrees upwards and twist in the plane
      of the ring from the closed to the open conformation. The closed rings have their
      nucleotide binding pockets closed by the intermediate domains, but in the open
      rings, the pocket is accessible.

PMID- 10926513
TI  - The effects of ligand binding on the backbone dynamics of the kringle 1 domain of
      human plasminogen.
AB  - The internal motions of the backbone nitrogen atoms of the kringle 1 domain of
      human plasminogen (K1(Pg)) were examined in the absence and presence of the
      ligand, epsilon-aminocaproic acid. These dynamic properties were determined from
      (15)N NMR relaxation data in terms of the extended model-free parameters. The
      model of isotropic reorientation was found sufficient to account for overall
      molecular tumbling for both apo and EACA-bound K1(Pg). The global rotational
      correlation time (tau(m)) for apo-K1(Pg) was 5.87(+/-0.01) ns, while the tau(m)
      for ligand-bound K1(Pg) was 5.20(+/-0.01) ns, suggesting that perhaps some small
      degree of aggregation occurred in the apo form of the kringle module.
      Complexation of K1(Pg) with ligand mainly reduced those internal motions that
      occurred on a 100 ps to 5 ns time-scale. The magnitude of the chemical exchange
      was also attenuated upon ligand binding. These data are consistent with studies
      employing other approaches that suggest that the binding pocket is preformed in
      K1(Pg).

PMID- 10926514
TI  - A role for upstream RNA structure in facilitating the catalytic fold of the
      genomic hepatitis delta virus ribozyme.
AB  - Hepatitis delta virus (HDV) has a circular RNA genome that replicates by a double
      rolling-circle mechanism. The genomic and antigenomic versions of HDV contain a
      ribozyme that undergoes cis-cleavage, thereby processing the transcript into unit
      length monomers. A genomic HDV transcript containing 30 nucleotides immediately
      upstream of the cleavage site was found to have attenuated self-cleavage.
      Structure mapping and site-directed mutagenesis revealed an inhibitory stretch
      consisting of upstream nucleotides -24 to -15 that forms a long-range pairing,
      termed Alt 1, with the 3' strand of P2 (P2(3')) located at the very 3'-end of the
      ribozyme. Two other alternative pairings were found, Alt 2, which involves
      upstream nucleotide-ribozyme interactions, and Alt 3, which involves ribozyme
      ribozyme interactions. Self-cleavage was rescued 2700 to 20,000-fold by adding
      DNA oligomers, which sequester the -24/-15 inhibitory stretch in trans.
      Surprisingly, co-transcriptional self-cleavage occurs when the number of upstream
      nucleotides is increased to 54. Computer prediction and structure mapping support
      the existence of an unusually stable upstream hairpin involving nucleotides -54
      to -18, termed P(-1)/L(-1), which sequesters the majority of the -24/-15
      inhibitory stretch in cis. This hairpin is followed by a stretch of single
      stranded pyrimidine-rich nucleotides, termed J(-1/1). Sequence comparison
      suggests that the P(-1)/L(-1)/J(-1/1) motif is conserved among known genomic HDV
      isolates, and that the J(-1/1) stretch is conserved among antigenomic HDV
      isolates. Lastly, the secondary structure of the Alt 1-containing ribozyme
      provides insight into possible folding intermediates of the ribozyme.

PMID- 10926515
TI  - Three-dimensional fold of the human AQP1 water channel determined at 4 A
      resolution by electron crystallography of two-dimensional crystals embedded in
      ice.
AB  - Here, we present a three-dimensional (3D) density map of deglycosylated, human
      erythrocyte aquaporin 1 (AQP1) determined at 4 A resolution in plane and
      approximately 7 A resolution perpendicular to the bilayer. The map was calculated
      by analyzing images and electron diffraction patterns recorded from tilted (up to
      60 degrees ), ice-embedded, frozen-hydrated 2D crystals of AQP1 in lipid bilayer
      membranes. This map significantly extends the findings related to the folding of
      the AQP1 polypeptide chain determined by us at a lower, 7 A by approximately 20
      A, resolution. The solvent-accessible volume within a monomer has a vestibular
      architecture, with a narrow, approximately 6.5 A diameter constriction near the
      center of the bilayer, where the location of the water-selective channel is
      postulated to exist. The clearly resolved densities for the transmembrane helices
      display the protrusions expected for bulky side-chains. The density in the
      interior of the helix barrel (putative NPA box region) is better resolved
      compared to our previous map, suggesting clearer linkage to some of the helices,
      and it may harbor short stretches of alpha-helix. At the bilayer extremities,
      densities for some of the inter-helix hydrophilic loops are visible. Consistent
      with these observed inter-helix connections, possible models for the threading of
      the AQP1 polypeptide chain are presented. A preferred model is deduced that
      agrees with the putative locations of a group of aromatic residues in the amino
      acid sequence and in the 3D density map.

PMID- 10926516
TI  - Structure of 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase from
      Escherichia coli: comparison of the Mn(2+)*2-phosphoglycolate and the Pb(2+)*2
      phosphoenolpyruvate complexes and implications for catalysis.
AB  - The crystal structure of the phenylalanine-regulated 3-deoxy-D-arabino
      heptulosonate-7-phosphate synthase (DAHPS) from Escherichia coli in complex with
      Mn(2+) and the substrate analog, 2-phosphoglycolate (PGL), was determined by
      molecular replacement using X-ray diffraction data to 2.0 A resolution.
      DAHPS*Mn*PGL crystallizes in space group C2 (a=210.4 A, b=53.2 A, c=149.4 A,
      beta=116.1 degrees ) with its four (beta/alpha)(8) barrel subunits related by non
      crystallographic 222 symmetry. The refinement was carried out without non
      crystallographic symmetry restraints and yielded agreement factors of R=20.9 %
      and R(free)=23.9 %. Mn(2+), the most efficient metal activator, is coordinated by
      the same four side-chains (Cys61, His268, Glu302 and Asp326) as is the poorly
      activating Pb(2+). A fifth ligand is a well-defined water molecule, which is
      within hydrogen bonding distance to an essential lysine residue (Lys97). The
      distorted octahedral coordination sphere of the metal is completed by PGL, which
      replaces the substrate, 2-phosphoenolpyruvate (PEP), in the active site. However,
      unlike PEP in the Pb*PEP complex, PGL binds the Mn(2+) via one of its carboxylate
      oxygen atoms. A model of the active site is discussed in which PEP binds in the
      same orientation as does PGL in the DAHPS*Mn*PGL structure and the phosphate of
      E4P is tethered at the site of a bound sulfate anion. The re face of E4P can be
      positioned to interact with the si face of PEP with only small movement of the
      protein.

PMID- 10926517
TI  - The crystal structure of yeast phenylalanine tRNA at 2.0 A resolution: cleavage
      by Mg(2+) in 15-year old crystals.
AB  - We have re-determined the crystal structure of yeast tRNA(Phe) to 2. 0 A
      resolution using 15 year old crystals. The accuracy of the new structure, due
      both to higher resolution data and formerly unavailable refinement methods,
      consolidates the previous structural information, but also reveals novel details.
      In particular, the water structure around the tightly bound Mg(2+) is now clearly
      resolved, and hence provides more accurate information on the geometry of the
      magnesium-binding sites and the role of water molecules in coordinating the metal
      ions to the tRNA. We have assigned a total of ten magnesium ions and identified a
      partly conserved geometry for high-affinity Mg(2+ )binding. In the electron
      density map there is also clear density for a spermine molecule binding in the
      major groove of the TPsiC arm and also contacting a symmetry-related tRNA
      molecule. Interestingly, we have also found that two specific regions of the tRNA
      in the crystals are partially cleaved. The sites of hydrolysis are within the D
      and anticodon loops in the vicinity of Mg(2+).

PMID- 10926518
TI  - Sensory mechanism of oxygen sensor FixL from Rhizobium meliloti:
      crystallographic, mutagenesis and resonance Raman spectroscopic studies.
AB  - FixL of Rhizobium meliloti (RmFixL) is a sensor histidine kinase of the two
      component system, which regulates the expression of the genes related to nitrogen
      fixation in the root nodule in response to the O(2) levels. The crystal structure
      of the sensor domain of FixL (RmFixLH), which contains a heme (Fe-porphyrin) as a
      sensing site, was determined at 1.4 A resolution. Based on the structural and
      spectroscopic analyses, we propose the O(2) sensing mechanism that differs from
      the case proposed in BjFixLH as follows; conformational changes in the F/G loop,
      which are induced by steric repulsion between the bent-bound O(2) and the Ile209
      side-chain, would be transmitted to the histidine kinase domain. Interaction
      between the iron-bound O(2) and Ile209 was also observed in the resonance Raman
      spectra of RmFixLH as evidenced by the fact that the Fe-O(2) and Fe-CN stretching
      frequencies were shifted from 575 to 570 cm(-1) (Fe-O(2)), and 504 to 499 cm(-1),
      respectively, as the result of the replacement of Ile209 with an Ala residue. In
      the I209A mutant of RmFixL, the O(2) sensing activity was destroyed, thus
      confirming our proposed mechanism.

PMID- 10926519
TI  - The crystal structure of adenylosuccinate lyase from Pyrobaculum aerophilum
      reveals an intracellular protein with three disulfide bonds.
AB  - Adenylosuccinate lyase catalyzes two separate reactions in the de novo purine
      biosynthetic pathway. Through its dual action in this pathway, adenylosuccinate
      lyase plays an integral part in cellular replication and metabolism. Mutations in
      the human enzyme can result in severe neurological disorders, including mental
      retardation with autistic features. The crystal structure of adenylosuccinate
      lyase from the hyperthermophilic archaebacterium Pyrobaculum aerophilum has been
      determined to 2.1 A resolution. Although both the fold of the monomer and the
      architecture of the tetrameric assembly are similar to adenylosuccinate lyase
      from the thermophilic eubacterium Thermotoga maritima, the archaebacterial lyase
      contains unique features. Surprisingly, the structure of adenylosuccinate lyase
      from P. aerophilum reveals that this intracellular protein contains three
      disulfide bonds that contribute significantly to its stability against thermal
      and chemical denaturation. The observation of multiple disulfide bonds in the
      recombinant form of the enzyme suggests the need for further investigations into
      whether the intracellular environment of P. aerophilum, and possibly other
      hyperthermophiles, may be compatible with protein disulfide bond formation. In
      addition, the protein is shorter in P. aerophilum than it is in other organisms.
      This abbreviation results from an internal excision of a cluster of helices that
      may be involved in protein-protein interactions in other organisms and may relate
      to the observed clinical effects of human mutations in that region.

PMID- 10926520
TI  - Crystal structure of glycosyltrehalose trehalohydrolase from the
      hyperthermophilic archaeum Sulfolobus solfataricus.
AB  - The crystal structure of glycosyltrehalose trehalohydrolase from the
      hyperthermophilic archaeum Sulfolobus solfataricus KM1 has been solved by
      multiple isomorphous replacement. The enzyme is an alpha-amylase (family 13) with
      unique exo-amylolytic activity for glycosyltrehalosides. It cleaves the alpha-1,4
      glycosidic bond adjacent to the trehalose moiety to release trehalose and
      maltooligo saccharide. Unlike most other family 13 glycosidases, the enzyme does
      not require Ca(2+) for activity, and it contains an N-terminal extension of
      approximately 100 amino acid residues that is homologous to N-terminal domains
      found in many glycosidases that recognize branched oligosaccharides.
      Crystallography revealed the enzyme to exist as a homodimer covalently linked by
      an intermolecular disulfide bond at residue C298. The existence of the
      intermolecular disulfide bond was confirmed by biochemical analysis and
      mutagenesis. The N-terminal extension forms an independent domain connected to
      the catalytic domain by an extended linker. The functionally essential Ca(2+)
      binding site found in the B domain of alpha-amylases and many other family 13
      glycosidases was found to be replaced by hydrophobic packing interactions. The
      enzyme also contains a very unusual excursion in the (beta/alpha)(8) barrel
      structure of the catalytic domain. This excursion originates from the bottom of
      the (beta/alpha)(8) barrel between helix 6 and strand 7, but folds upward in a
      distorted alpha-hairpin structure to form a part of the substrate binding cleft
      wall that is possibly critical for the enzyme's unique substrate selectivity.
      Participation of an alpha-beta loop in the formation of the substrate binding
      cleft is a novel feature that is not observed in other known (beta/alpha)(8)
      enzymes.

PMID- 10926521
TI  - Crystals of the urokinase type plasminogen activator variant beta(c)-uPAin
      complex with small molecule inhibitors open the way towards structure-based drug
      design.
AB  - Urokinase is a serine protease involved in cancer growth and metastasis. Here we
      present the first urokinase crystal structure in complex with reversible
      inhibitors at 2.1 and 2.6 A resolution. These inhibitor complex structures have
      been obtained from crystals of engineered urokinase type plasminogen activator
      designed to obtain a crystal form open for inhibitor soaking. The mutant C122S
      loses its flexible A-chain upon activation cleavage and crystallizes in the
      presence of benzamidine, which was later displaced by the desired inhibitor. This
      new soakable crystal form turned out to be of great value in the process of
      structure-based drug design. The evaluated binding mode of amiloride, and UKI-1D
      revealed a new subsite of the primary specificity pocket of urokinase that will
      be employed in the future ligand optimisation process.

PMID- 10926522
TI  - Solution conformation and amyloid-like fibril formation of a polar peptide
      derived from a beta-hairpin in the OspA single-layer beta-sheet.
AB  - A 23-residue peptide termed BH(9-10) was designed based on a beta-hairpin segment
      of the single-layer beta-sheet region of Borrelia OspA protein. The peptide
      contains a large number of charged amino acid residues, and it does not follow
      the amphipathic pattern that is commonly found in natural beta-sheets. In aqueous
      solution, the peptide was highly soluble and flexible, with a propensity to form
      a non-native beta-turn. Trifluoroethanol (TFE) stabilized a native-like beta-turn
      in BH(9-10). TFE also decreased the level of solubility of the peptide, resulting
      in peptide precipitation. The precipitation process accompanied a conformational
      conversion to a beta-sheet structure, as judged with circular dichroism
      spectroscopy. The precipitate was found to be fibrils similar to those associated
      with human amyloid diseases. The fibrillization kinetics depended on peptide and
      TFE concentrations, and had a nucleation step followed by an assembly step. The
      fibrillization was reversible, and the dissociation reaction involved two phases.
      TFE appears to induce the fibrils by stabilizing a beta-sheet conformation of the
      peptide that optimally satisfies hydrogen bonding and electrostatic
      complementarity. This TFE-induced fibrillization is quite unusual, because most
      amyloidogenic peptides form fibrils in aqueous solution and TFE disrupts these
      fibrils. Nevertheless, the BH(9-10) fibrils have similar structure to other
      fibrils, supporting the emerging idea that polypeptides possess an intrinsic
      ability to form amyloid-like fibrils. The high level of solubility of BH(9-10),
      the ability to precisely control fibril formation and dissociation, and the high
      resolution structure of the same sequence in the beta-hairpin conformation in the
      OspA protein provide a tractable experimental system for studying the fibril
      formation mechanism.

PMID- 10926523
TI  - NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi
      RNA packaging signal. Implications for genome recognition.
AB  - The RNA genome of the human immunodeficiency virus type-1 (HIV-1) contains a
      approximately 120 nucleotide Psi-packaging signal that is recognized by the
      nucleocapsid (NC) domain of the Gag polyprotein during virus assembly. The Psi
      site contains four stem-loops (SL1-SL4) that possess overlapping and possibly
      redundant functions. The present studies demonstrate that the 19 residue SL2 stem
      loop binds NC with affinity (K(d)=110(+/-50) nM) similar to that observed for NC
      binding to SL3 (K(d)=170(+/-65) nM) and tighter than expected on the basis of
      earlier work, suggesting that NC-SL2 interactions probably play a direct role in
      the specific recognition and packaging of the full-length, unspliced genome. The
      structure of the NC-SL2 complex was determined by heteronuclear NMR methods using
      (15)N,(13)C-isotopically labeled NC protein and SL2 RNA. The N and C-terminal
      "zinc knuckles" (Cys-X(2)-Cys-X(4)-His-X(4)-Cys; X=variable amino acid) of HIV-1
      NC bind to exposed guanosine bases G9 and G11, respectively, of the G8-G9-U10-G11
      tetraloop, and residues Lys3-Lys11 of the N-terminal tail forms a 3(10) helix
      that packs against the proximal zinc knuckle and interacts with the RNA stem.
      These structural features are similar to those observed previously in the NMR
      structure of NC bound to SL3. Other features of the complex are substantially
      different. In particular, the N-terminal zinc knuckle interacts with an A-U-A
      base triple platform in the minor groove of the SL2 RNA stem, but binds to the
      major groove of SL3. In addition, the relative orientations of the N and C
      terminal zinc knuckles differ in the NC-SL2 and NC-SL3 complexes, and the side
      chain of Phe6 makes minor groove hydrophobic contacts with G11 in the NC-SL2
      complex but does not interact with RNA in the NC-SL3 complex. Finally, the N
      terminal helix of NC interacts with the phosphodiester backbone of the SL2 RNA
      stem mainly via electrostatic interactions, but does not bind in the major groove
      or make specific H-bonding contacts as observed in the NC-SL3 structure. These
      findings demonstrate that NC binds in an adaptive manner to SL2 and SL3 via
      different subsets of inter and intra-molecular interactions, and support a genome
      recognition/packaging mechanism that involves interactions of two or more NC
      domains of assembling HIV-1 Gag molecules with multiple Psi-site stem-loop
      packaging elements during the early stages of retrovirus assembly.

PMID- 10926525
TI  - A view of dynamics changes in the molten globule-native folding step by
      quasielastic neutron scattering.
AB  - In order to understand the changes in protein dynamics that occur in the final
      stages of protein folding, we have used neutron scattering to probe the
      differences between a protein in its folded state and the molten globule states.
      The internal dynamics of bovine alpha-lactalbumin (BLA) and its molten globules
      (MBLA) have been examined using incoherent, quasielastic neutron scattering
      (IQNS). The IQNS results show length scale dependent, pico-second dynamics
      changes on length scales from 3.3 to 60 A studied. On shorter-length scales, the
      non-exchangeable protons undergo jump motions over potential barriers, as those
      involved in side-chain rotamer changes. The mean potential barrier to local jump
      motions is higher in BLA than in MBLA, as might be expected. On longer length
      scales, the protons undergo spatially restricted diffusive motions with the
      diffusive motions being more restricted in BLA than in MBLA. Both BLA and MBLA
      have similar mean square amplitudes of high frequency motions comparable to the
      chemical bond vibrational motions. Bond vibrational motions thus do not change
      significantly upon folding. Interestingly, the quasielastic scattering
      intensities show pronounced maxima for both BLA and MBLA, suggesting that
      "clusters" of atoms are moving collectively within the proteins on picosecond
      time scales. The correlation length, or "the cluster size", of such atom clusters
      moving collectively is dramatically reduced in the molten globules with the
      correlation length being 6.9 A in MBLA shorter than that of 18 A in BLA. Such
      collective motions may be important for the stability of the folded state, and
      may influence the protein folding pathways from the molten globules.

PMID- 10926524
TI  - Solution structure of the catalytic domain of human collagenase-3 (MMP-13)
      complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with
      stromelysin-1 and collagenase-1.
AB  - The full three-dimensional structure of the catalytic domain of human collagenase
      3 (MMP-13) complexed to a potent, sulfonamide hydroxamic acid inhibitor (CGS
      27023) has been determined by NMR spectroscopy. The results reveal a core domain
      for the protein consisting of three alpha-helices and five beta-sheet strands
      with an overall tertiary fold similar to the catalytic domains of other matrix
      metalloproteinase family members. The S1' pocket, which is the major site of
      hydrophobic binding interaction, was found to be a wide cleft spanning the length
      of the protein and presenting facile opportunity for inhibitor extension deep
      into the pocket. Comparison with the reported X-ray structure of collagenase-3
      showed evidence of flexibility for the loop region flanking the S1' pocket in
      both NMR and X-ray data. This flexibility was corroborated by NMR dynamics
      studies. Inhibitor binding placed the methoxy phenyl ring in the S1' pocket with
      the remainder of the molecule primarily solvent-exposed. The binding mode for
      this inhibitor was found to be similar with respect to stromelysin-1 and
      collagenase-1; however, subtle comparative differences in the interactions
      between inhibitor and enzyme were observed for the three MMPs that were
      consistent with their respective binding potencies.

PMID- 10926526
TI  - Tissue inhibitor of metalloproteinases-1 undergoes microsecond to millisecond
      motions at sites of matrix metalloproteinase-induced fit.
AB  - The N-terminal, matrix metalloproteinase (MMP)-inhibitory fragment of
      recombinant, human tissue inhibitor of metalloproteinases (TIMP-1) exhibits
      varied backbone dynamics and rigidity. Most striking is the presence of chemical
      exchange in the MMP-binding ridge reported to undergo conformational change upon
      MMP binding. Conformational exchange fluctuations in microseconds to milliseconds
      map to the sites of MMP-induced fit at residues Val29 through Leu34 of the AB
      loop and to the Ala65 and Cys70 "hinges" of the CD loop of TIMP-1. Slow chemical
      exchange is also present at the type I turn of the EF loop at the base of the MMP
      binding ridge. These functional slow motions and other fast internal motions are
      evident from backbone (15)N spin relaxation at 500 and 750 MHz, whether
      interpreted by the model-free formalism with axial diffusion anisotropy or by the
      reduced spectral density approach. The conformational exchange is confirmed by
      its deviation from the trend between R(2) and the cross-correlation rate eta. The
      magnetic field-dependence indicates that the chemical exchange broadening in the
      AB and CD loops is fast on the time-scale of chemical shift differences. The
      conformational exchange rates for most of these exchanging residues, which can
      closely approach MMP, appear to be a few thousand to several thousand per second.
      The slow dynamics of the TIMP-1 AB loop contrast the picosecond to nanosecond
      dynamics reported in the longer TIMP-2 AB loop.

PMID- 10926527
TI  - Is polyproline II helix the killer conformation? A Raman optical activity study
      of the amyloidogenic prefibrillar intermediate of human lysozyme.
AB  - The amyloidogenic prefibrillar partially denatured intermediate of human
      lysozyme, prepared by heating the native protein to 57 degrees C at pH 2.0, was
      studied using Raman optical activity (ROA). A positive band in the room
      temperature ROA spectrum of the native protein at approximately 1345 cm(-1),
      assigned to a hydrated form of alpha-helix, is not present in that of the
      prefibrillar intermediate, where a new strong positive band at approximately 1318
      cm(-1) appears instead that is assigned to the poly(l-proline) II (PPII)-helical
      conformation. A sharp negative band at approximately 1241 cm(-1) in the native
      protein, assigned to beta-strand, shows little change in the ROA spectrum of the
      prefibrillar intermediate. The disappearance of a positive ROA band at
      approximately 1551 cm(-1) assigned to vibrations of tryptophan side-chains
      indicates that major conformational changes have occurred among the five
      tryptophan residues present in human lysozyme, four of which are located in the
      alpha-domain. The various ROA data suggest that a substantial loss of tertiary
      structure has occurred in the prefibrillar intermediate and that this is located
      more in the alpha-domain than in the beta-domain. There is no evidence for any
      increase in beta-structure. The ROA spectrum of hen lysozyme, which does not form
      amyloid fibrils so readily, remains much more native-like on heating to 57
      degrees C at pH 2.0. The thermal behaviour of the alanine-rich alpha-helical
      peptide AK21 in aqueous solution was found to be similar to that of human
      lysozyme. Hydrated alpha-helix therefore appears to readily undergo a
      conformational change to PPII structure on heating, which may be a key step in
      the conversion of alpha-helix into beta-sheet in the formation of amyloid fibrils
      in human lysozyme. Since it is extended, flexible, lacks intrachain hydrogen
      bonds and is fully hydrated in aqueous solution, PPII helix has the appropriate
      characteristics to be implicated as a critical conformational element in many
      conformational diseases. Disorder of the PPII type may be a sine qua non for the
      formation of regular fibrils; whereas the more dynamic disorder of the random
      coil may lead only to amorphous aggregates.

PMID- 10926528
TI  - Crystal structure of rhodopsin: A G protein-coupled receptor.
AB  - Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors
      (GPCRs) respond to a variety of different external stimuli and activate G
      proteins. GPCRs share many structural features, including a bundle of seven
      transmembrane alpha helices connected by six loops of varying lengths. We
      determined the structure of rhodopsin from diffraction data extending to 2.8
      angstroms resolution. The highly organized structure in the extracellular region,
      including a conserved disulfide bridge, forms a basis for the arrangement of the
      seven-helix transmembrane motif. The ground-state chromophore, 11-cis-retinal,
      holds the transmembrane region of the protein in the inactive conformation.
      Interactions of the chromophore with a cluster of key residues determine the
      wavelength of the maximum absorption. Changes in these interactions among
      rhodopsins facilitate color discrimination. Identification of a set of residues
      that mediate interactions between the transmembrane helices and the cytoplasmic
      surface, where G-protein activation occurs, also suggests a possible structural
      change upon photoactivation.

PMID- 10926529
TI  - Ferromagnetism stabilized by lattice distortion at the surface of the p-wave
      superconductor Sr(2)RuO(4)
AB  - Ferromagnetic (FM) spin fluctuations are believed to mediate the spin-triplet
      pairing for the p-wave superconductivity in Sr(2)RuO(4). Our experiments show
      that, at the surface, a bulk soft-phonon mode freezes into a static lattice
      distortion associated with an in-plane rotation of the RuO(6) octahedron. First
      principle calculations confirm this structure and predict a FM ground state at
      the surface. This coupling between structure and magnetism in the environment of
      broken symmetry at the surface allows a reconsideration of the coupling mechanism
      in the bulk.

PMID- 10926530
TI  - Radiation tolerance of complex oxides
AB  - The radiation performance of a variety of complex oxides is predicted on the
      basis of a material's propensity to accommodate lattice point defects. The
      calculations indicate that a particular class of oxides possessing the fluorite
      crystal structure should accept radiation-induced defects into their lattices far
      more readily than a structurally similar class of oxides based on the pyrochlore
      crystal structure. Preliminary radiation damage experiments substantiate the
      prediction that fluorites are inherently more radiation resistant than
      pyrochlores. These results may permit the chemical durability and radiation
      tolerance of potential hosts for actinides and radioactive wastes to be tailored.

PMID- 10926531
TI  - Aggregation-based crystal growth and microstructure development in natural iron
      oxyhydroxide biomineralization products.
AB  - Crystals are generally considered to grow by attachment of ions to inorganic
      surfaces or organic templates. High-resolution transmission electron microscopy
      of biomineralization products of iron-oxidizing bacteria revealed an alternative
      coarsening mechanism in which adjacent 2- to 3-nanometer particles aggregate and
      rotate so their structures adopt parallel orientations in three dimensions.
      Crystal growth is accomplished by eliminating water molecules at interfaces and
      forming iron-oxygen bonds. Self-assembly occurs at multiple sites, leading to a
      coarser, polycrystalline material. Point defects (from surface-adsorbed
      impurities), dislocations, and slabs of structurally distinct material are
      created as a consequence of this growth mechanism and can dramatically impact
      subsequent reactivity.

PMID- 10926532
TI  - A cyclic carbanionic valence isomer of a carbocation: diphosphino analogs of
      diaminocarbocations
AB  - Diaminocarbocations (or amidinium salts) feature a three-center 4pi electron
      system with an open planar structure. Their 2pi electron three-membered cyclic
      valence isomers, in which the carbon atom bears a negative charge, are predicted
      to be about 541 kilojoules per mole higher in energy than the open form. This
      isomer has not been identified yet. In contrast, the attempted synthesis of a
      diphosphorus analog of amidinium salts leads to the cyclic carbanionic form.
      There is no precedent for such a transformation of a carbocationic center into a
      carbanionic center, but with the help of heavier main-group elements, numerous
      examples can be imagined. This approach will enable the preparation of many
      unknown structural moieties that are difficult or even impossible to access in
      the corresponding carbon and nitrogen series.

PMID- 10926533
TI  - Atmospheric influence of Earth's earliest sulfur cycle
AB  - Mass-independent isotopic signatures for delta(33)S, delta(34)S, and delta(36)S
      from sulfide and sulfate in Precambrian rocks indicate that a change occurred in
      the sulfur cycle between 2090 and 2450 million years ago (Ma). Before 2450 Ma,
      the cycle was influenced by gas-phase atmospheric reactions. These atmospheric
      reactions also played a role in determining the oxidation state of sulfur,
      implying that atmospheric oxygen partial pressures were low and that the roles of
      oxidative weathering and of microbial oxidation and reduction of sulfur were
      minimal. Atmospheric fractionation processes should be considered in the use of
      sulfur isotopes to study the onset and consequences of microbial fractionation
      processes in Earth's early history.

PMID- 10926534
TI  - Phosphate depletion in the western North Atlantic Ocean.
AB  - Surface waters of the subtropical Sargasso Sea contain dissolved inorganic
      phosphate (DIP) concentrations of 0.2 to 1.0 nanomolar, which are sufficiently
      low to result in phosphorus control of primary production. The DIP concentrations
      in this area (which receives high inputs of iron-rich dust from arid regions of
      North Africa) are one to two orders of magnitude lower than surface levels in the
      North Pacific (where eolian iron inputs are much lower and water column
      denitrification is much more substantial). These data indicate a severe relative
      phosphorus depletion in the Atlantic. We hypothesize that nitrogen versus
      phosphorus limitation of primary production in the present-day ocean may be
      closely linked to iron supply through control of dinitrogen (N2) fixation, an
      iron-intensive metabolic process. Although the oceanic phosphorus inventory may
      set the upper limit for the total amount of organic matter produced in the ocean
      over geological time scales, at any instant in geological time, oceanic primary
      production may fall below this limit because of a persistent insufficient iron
      supply. By controlling N2 fixation, iron may control not only nitrogen versus
      phosphorus limitation but also carbon fixation and export stoichiometry and hence
      biological sequestration of atmospheric carbon dioxide.

PMID- 10926535
TI  - The response of two contrasting limestone grasslands to simulated climate change.
AB  - Two different UK limestone grasslands were exposed to simulated climate change
      with the use of nonintrusive techniques to manipulate local climate over 5 years.
      Resistance to climate change, defined as the ability of a community to maintain
      its composition and biomass in response to environmental stress, could be
      explained by reference to the functional composition and successional status of
      the grasslands. The more fertile, early-successional grassland was much more
      responsive to climate change. Resistance could not be explained by the particular
      climates experienced by the two grasslands. Productive, disturbed landscapes
      created by modern human activity may prove more vulnerable to climate change than
      older, traditional landscapes.

PMID- 10926536
TI  - CikA, a bacteriophytochrome that resets the cyanobacterial circadian clock.
AB  - The circadian oscillator of the cyanobacterium Synechococcus elongatus, like
      those in eukaryotes, is entrained by environmental cues. Inactivation of the gene
      cikA (circadian input kinase) shortens the circadian period of gene expression
      rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset
      of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The
      CikA protein sequence reveals that it is a divergent bacteriophytochrome with
      characteristic histidine protein kinase motifs and a cryptic response regulator
      motif. CikA is likely a key component of a pathway that provides environmental
      input to the circadian oscillator in S. elongatus.

PMID- 10926537
TI  - Cloning of the Arabidopsis clock gene TOC1, an autoregulatory response regulator
      homolog.
AB  - The toc1 mutation causes shortened circadian rhythms in light-grown Arabidopsis
      plants. Here, we report the same toc1 effect in the absence of light input to the
      clock. We also show that TOC1 controls photoperiodic flowering response through
      clock function. The TOC1 gene was isolated and found to encode a nuclear protein
      containing an atypical response regulator receiver domain and two motifs that
      suggest a role in transcriptional regulation: a basic motif conserved within the
      CONSTANS family of transcription factors and an acidic domain. TOC1 is itself
      circadianly regulated and participates in a feedback loop to control its own
      expression.

PMID- 10926538
TI  - Pif1p helicase, a catalytic inhibitor of telomerase in yeast.
AB  - Mutations in the yeast Saccharomyces cerevisiae PIF1 gene, which encodes a 5'-to
      3' DNA helicase, cause telomere lengthening and a large increase in the formation
      rate of new telomeres. Here, we show that Pif1p acts by inhibiting telomerase
      rather than telomere-telomere recombination, and this inhibition requires the
      helicase activity of Pif1p. Overexpression of enzymatically active Pif1p causes
      telomere shortening. Thus, Pif1p is a catalytic inhibitor of telomerase-mediated
      telomere lengthening. Because Pif1p is associated with telomeric DNA in vivo, its
      effects on telomeres are likely direct. Pif1p-like helicases are found in diverse
      organisms, including humans. We propose that Pif1p-mediated inhibition of
      telomerase promotes genetic stability by suppressing telomerase-mediated healing
      of double-strand breaks.

PMID- 10926539
TI  - Pol kappa: A DNA polymerase required for sister chromatid cohesion.
AB  - Establishment of cohesion between sister chromatids is coupled to replication
      fork passage through an unknown mechanism. Here we report that TRF4, an
      evolutionarily conserved gene necessary for chromosome segregation, encodes a DNA
      polymerase with beta-polymerase-like properties. A double mutant in the redundant
      homologs, TRF4 and TRF5, is unable to complete S phase, whereas a trf4 single
      mutant completes a presumably defective S phase that results in a failure of
      cohesion between the replicated sister chromatids. This suggests that TRFs are a
      key link in the coordination between DNA replication and sister chromatid
      cohesion. Trf4 and Trf5 represent the fourth class of essential nuclear DNA
      polymerases (designated DNA polymerase kappa) in Saccharomyces cerevisiae and
      probably in all eukaryotes.

PMID- 10926540
TI  - Cell-cell signaling and movement by the floral transcription factors LEAFY and
      APETALA1.
AB  - LEAFY (LFY) and APETALA1 (AP1) encode unrelated transcription factors that
      activate overlapping sets of homeotic genes in Arabidopsis flowers. Sector
      analysis and targeted expression in transgenic plants were used to study whether
      LFY and AP1 can participate in cell-cell signaling between and within different
      layers of the floral meristem. LFY signaled equally well from all layers and had
      substantial long-range action within layers. Nonautonomous action of LFY was
      accompanied by movement of the protein to adjacent cells, where it directly
      activated homeotic target genes. In contrast, AP1 had only limited nonautonomous
      effects, apparently mediated by downstream genes because activation of early
      target genes by AP1 was cell-autonomous.

PMID- 10926541
TI  - Role of adenine nucleotide translocator 1 in mtDNA maintenance.
AB  - Autosomal dominant progressive external ophthalmoplegia is a rare human disease
      that shows a Mendelian inheritance pattern, but is characterized by large-scale
      mitochondrial DNA (mtDNA) deletions. We have identified two heterozygous missense
      mutations in the nuclear gene encoding the heart/skeletal muscle isoform of the
      adenine nucleotide translocator (ANT1) in five families and one sporadic patient.
      The familial mutation substitutes a proline for a highly conserved alanine at
      position 114 in the ANT1 protein. The analogous mutation in yeast caused a
      respiratory defect. These results indicate that ANT has a role in mtDNA
      maintenance and that a mitochondrial disease can be caused by a dominant
      mechanism.

PMID- 10926542
TI  - Involvement of cellular caveolae in bacterial entry into mast cells.
AB  - Caveolae are subcellular structures implicated in the import and transcytosis of
      macromolecules and in transmembrane signaling. To date, evidence for the
      existence of caveolae in hematopoietic cells has been ambiguous. Caveolae were
      detected in the microvilli and intracellular vesicles of cultured mouse bone
      marrow-derived mast cells (BMMCs). CD48, a receptor for FimH-expressing (type 1
      fimbriated) Escherichia coli, was specifically localized to plasmalemmal caveolae
      in BMMCs. The involvement of caveolae in bacterial entry into BMMCs was indicated
      because caveolae-disrupting and -usurping agents specifically blocked E. coli
      entry, and markers of caveolae were actively recruited to sites of bacterial
      entry. The formation of bacteria-encapsulating caveolar chambers in BMMCs
      represents a distinct mechanism of microbial entry into phagocytes.

PMID- 10926543
TI  - G(s) protein dysfunction in allergen-challenged human isolated passively
      sensitized bronchi.
AB  - We studied the intracellular mechanisms of allergen-induced beta(2)-adrenoceptor
      dysfunction in human isolated passively sensitized bronchi. Sensitization was
      obtained by overnight incubation of bronchial rings with serum containing a high
      specific IgE level to Dermatophagoides but a low total IgE level. Allergen
      challenge was done by incubation with a Dermatophagoides mix. The G(s) protein
      stimulant cholera toxin (2 microg/ml) displaced the carbachol (CCh) concentration
      response curves of control and sensitized but not of challenged rings to the
      right. Cholera toxin (10 microg/ml) displaced the concentration-response curves
      to CCh of control, sensitized, and challenged rings to the right, but this effect
      was less in challenged rings. The effects of the G(i) protein inhibitor pertussis
      toxin (250 ng/ml or 1 microg/ml) on salbutamol concentration-relaxation curves
      did not differ significantly between challenged and sensitized rings. The
      adenylyl cyclase activator forskolin and the Ca(2+)-activated K(+)-channel opener
      NS-1619 relaxed CCh-contracted bronchial rings without significant differences
      between control, sensitized, and challenged rings. Neither G(i) nor G(s) alpha
      subunit expression differed between control, sensitized, and challenged tissues.
      We conclude that G(s) protein dysfunction may be a mechanism of allergen-induced
      beta(2)-adrenoceptor dysfunction in human isolated passively sensitized bronchi.

PMID- 10926544
TI  - Surfactant protein A enhances mycobacterial killing by rat macrophages through a
      nitric oxide-dependent pathway.
AB  - Surfactant-associated protein A (SP-A) is involved in surfactant homeostasis and
      host defense in the lung. We have previously demonstrated that SP-A specifically
      binds to and enhances the ingestion of bacillus Calmette-Guerin (BCG) organisms
      by macrophages. In the current study, we investigated the effect of SP-A on the
      generation of inflammatory mediators induced by BCG and the subsequent fate of
      ingested BCG organisms. Rat macrophages were incubated with BCG in the presence
      and absence of SP-A. Noningested BCG organisms were removed, and the release of
      tumor necrosis factor-alpha (TNF-alpha) and nitric oxide were measured at varying
      times. TNF-alpha and nitric oxide production induced by BCG were enhanced by SP
      A. In addition, SP-A enhanced the BCG-induced increase in the level of inducible
      nitric oxide synthase protein. Addition of antibodies directed against SPR210, a
      specific macrophage SP-A receptor, inhibited the SP-A-enhanced mediator
      production. BCG in the absence of SP-A showed increased growth over a 5-day
      period, whereas inclusion of SP-A dramatically inhibited BCG growth. Inhibition
      of nitric oxide production blocked BCG killing in the presence and absence of SP
      A. These results demonstrate that ingestion of SP-A-BCG complexes by rat
      macrophages leads to production of inflammatory mediators and increased
      mycobacterial killing.

PMID- 10926545
TI  - Beta(1)-integrins are involved in migration of human fetal tracheal epithelial
      cells and tubular morphogenesis.
AB  - Development of human fetal airways requires interaction of the respiratory
      epithelium and the extracellular matrix through integrins. Nevertheless, the
      specific roles of beta(1)-integrins during development and tubular morphogenesis
      are still unknown. To analyze beta(1)-integrin localization and influence during
      migration, we developed a model of human fetal tracheal explants growing on
      collagen and overlaid with a second layer of collagen to form a sandwich. In this
      configuration, cord and tubule formation proceeded normally but were inhibited by
      incubation with anti-beta(1)-integrin subunit antibodies. On a collagen matrix,
      beta(1)-integrins were immunolocalized on the entire plasma membrane of migrating
      epithelial cells and almost exclusively on the basal plasma membrane of
      nonmigratory epithelial cells. In a sandwich configuration, beta(1)-integrins
      became detectable in the cytoplasm of epithelial cells. Coating cultures with
      collagen transiently altered the morphology of migrating cells and their speed
      and direction of migration, whereas incubation with anti-beta(1)-integrin subunit
      antibodies irreversibly altered these parameters. These observations suggest that
      the matrix environment, by modulating beta(1)-integrin expression patterns, plays
      a key role during tubular morphogenesis of human fetal tracheal epithelium,
      principally by modulating epithelial cell migration.

PMID- 10926546
TI  - P2Y(2) receptor-stimulated phosphoinositide hydrolysis and Ca(2+) mobilization in
      tracheal epithelial cells.
AB  - Extracellular nucleotides have been implicated in the regulation of secretory
      function through the activation of P2 receptors in the epithelial tissues,
      including tracheal epithelial cells (TECs). In this study, experiments were
      conducted to characterize the P2 receptor subtype on canine TECs responsible for
      stimulating inositol phosphate (InsP(x)) accumulation and Ca(2+) mobilization
      using a range of nucleotides. The nucleotides ATP and UTP caused a concentration
      dependent increase in [(3)H]InsP(x) accumulation and Ca(2+) mobilization with
      comparable kinetics and similar potency. The selective agonists for P1, P2X, and
      P2Y(1) receptors, N(6)-cyclopentyladenosine and AMP, alpha,beta-methylene-ATP and
      beta, gamma-methylene-ATP, and 2-methylthio-ATP, respectively, had little effect
      on these responses. Stimulation of TECs with maximally effective concentrations
      of ATP and UTP showed no additive effect on [(3)H]InsP(x) accumulation. The
      response of a maximally effective concentration of either ATP or UTP was additive
      to the response evoked by bradykinin. Furthermore, ATP and UTP induced a cross
      desensitization in [(3)H]InsP(x) accumulation and Ca(2+) mobilization. These
      results suggest that ATP and UTP directly stimulate phospholipase C-mediated
      [(3)H]InsP(x) accumulation and Ca(2+) mobilization in canine TECs. P2Y(2)
      receptors may be predominantly mediating [(3)H]InsP(x) accumulation, and,
      subsequently, inositol 1,4,5-trisphosphate-induced Ca(2+) mobilization may
      function as the transducing mechanism for ATP-modulated secretory function of
      tracheal epithelium.

PMID- 10926548
TI  - Heparin-like molecules inhibit pulmonary vascular pericyte proliferation in
      vitro.
AB  - Proliferation of vascular pericytes (PCs), smooth muscle-like cells found in the
      distal microvasculature, contributes to vascular remodeling in pulmonary
      hypertension. The factors controlling lung PC quiescence in normal states are
      poorly understood. We demonstrate that exogenous heparin and heparan sulfate
      proteoglycans inhibit rat lung PC proliferation in vitro as does pulmonary
      vascular subendothelial matrix, particularly its heparan sulfate component.
      Heparin inhibits the intracellular alkalinization essential to proliferation, and
      we show that inhibition of alkalinization by 5-(N, N-dimethyl)amiloride also
      reduces PC proliferation. As shown by DNA staining and fluorescence-activated
      cell sorting analysis, heparin does not induce apoptosis in PCs. However, heparin
      maintains lung PCs in the G(0)/G(1) growth phase. Heparin induces production of
      p21, a potent inhibitor of cyclin-dependent kinases, thereby potentially
      identifying a fundamental mechanism by which heparin inhibits proliferation in
      smooth muscle-like cells. These studies establish additional similarities between
      lung PCs and smooth muscle cells and provide further understanding of growth
      control in the lung microvasculature. They also further support the rationale
      that heparin-like molecules might be therapeutically beneficial in pulmonary
      hypertension.

PMID- 10926547
TI  - K(+) channel inhibition, calcium signaling, and vasomotor tone in canine
      pulmonary artery smooth muscle.
AB  - We investigated the role of K(+) channels in the regulation of baseline
      intracellular free Ca(2+) concentration ([Ca(2+)](i)), alpha-adrenoreceptor
      mediated Ca(2+) signaling, and capacitative Ca(2+) entry in pulmonary artery
      smooth muscle cells (PASMCs). Inhibition of voltage-gated K(+) channels with 4
      aminopyridine (4-AP) increased the membrane potential and the resting [Ca(2+)](i)
      but attenuated the amplitude and frequency of the [Ca(2+)](i) oscillations
      induced by the alpha-agonist phenylephrine (PE). Inhibition of Ca(2+)-activated
      K(+) channels (with charybdotoxin) and inhibition (with glibenclamide) or
      activation of ATP-sensitive K(+) channels (with lemakalim) had no effect on
      resting [Ca(2+)](i) or PE-induced [Ca(2+)](i) oscillations. Thapsigargin was used
      to deplete sarcoplasmic reticulum Ca(2+) stores in the absence of extracellular
      Ca(2+). Under these conditions, 4-AP attenuated the peak and sustained components
      of capacitative Ca(2+) entry, which was observed when extracellular Ca(2+) was
      restored. Capacitative Ca(2+) entry was unaffected by charybdotoxin,
      glibenclamide, or lemakalim. In isolated pulmonary arterial rings, 4-AP increased
      resting tension and caused a leftward shift in the KCl dose-response curve. In
      contrast, 4-AP decreased PE-induced contraction, causing a rightward shift in the
      PE dose-response curve. These results indicate that voltage-gated K(+) channel
      inhibition increases resting [Ca(2+)](i) and tone in PASMCs but attenuates the
      response to PE, likely via inhibition of capacitative Ca(2+) entry.

PMID- 10926549
TI  - Effects of hypoxia in porcine pulmonary arterial myocytes: roles of K(V) channel
      and endothelin-1.
AB  - Effects of acute hypoxia on intracellular Ca(2+) concentration ([Ca(2+)](i)) and
      cell length were recorded simultaneously in proximal and distal pulmonary
      (PASMCs) and femoral (FASMCs) arterial smooth muscle cells. Reducing PO(2) from
      normoxia to severe hypoxia (PO(2) < 10 mmHg) caused small but significant
      decreases in length and a reversible increase in [Ca(2+)](i) in distal PASMCs and
      a small decrease in length in proximal PASMCs but had no effect in FASMCs, even
      though all three cell types contracted significantly to vasoactive agonists.
      Inhibition of voltage-dependent K(+) (K(V)) channel with 4-aminopyridine produced
      a greater increase in [Ca(2+)](i) in distal than in proximal PASMCs. In distal
      PASMCs, severe hypoxia caused a slight inhibition of K(V) currents; however, it
      elicited further contraction in the presence of 4-aminopyridine. Endothelin-1
      (10(-10) M), which itself did not alter cell length or [Ca(2+)](i), significantly
      potentiated the hypoxic contraction. These results suggest that hypoxia only has
      small direct effects on porcine PASMCs. These effects cannot be fully explained
      by inhibition of K(V) channels and were greatly enhanced via synergistic
      interactions with the endothelium-derived factor endothelin-1.

PMID- 10926550
TI  - Gene expression and function of adenosine A(2A) receptor in the rat carotid body.
AB  - The present study was undertaken to determine whether rat carotid bodies express
      adenosine (Ado) A(2A) receptors and whether this receptor is involved in the
      cellular response to hypoxia. Our results demonstrate that rat carotid bodies
      express the A(2A) and A(2B) Ado receptor mRNAs but not the A(1) or A(3) receptor
      mRNAs as determined by reverse transcriptase-polymerase chain reaction. In situ
      hybridization confirmed the expression of the A(2A) receptor mRNA.
      Immunohistochemical studies further showed that the A(2A) receptor is expressed
      in the carotid body and that it is colocalized with tyrosine hydroxylase in type
      I cells. Whole cell voltage-clamp studies using isolated type I cells showed that
      Ado inhibited the voltage-dependent Ca(2+) currents and that this inhibition was
      abolished by the selective A(2A) receptor antagonist ZM-241385. Ca(2+) imaging
      studies using fura 2 revealed that exposure to severe hypoxia induced elevation
      of intracellular Ca(2+) concentration ([Ca(2+)](i)) in type I cells and that
      extracellularly applied Ado significantly attenuated the hypoxia-induced
      elevation of [Ca(2+)](i). Taken together, our findings indicate that A(2A)
      receptors are present in type I cells and that activation of A(2A) receptors
      modulates Ca(2+) accumulation during hypoxia. This mechanism may play a role in
      regulating intracellular Ca(2+) homeostasis and cellular excitability during
      hypoxia.

PMID- 10926551
TI  - Early abnormalities of pulmonary vascular development in the Fawn-Hooded rat
      raised at Denver's altitude.
AB  - The Fawn-Hooded rat (FHR) is a genetic strain that has been extensively studied
      as a model of primary pulmonary hypertension in adult rats. Based on our recent
      observations that alveolar number and pulmonary arterial density are reduced in
      FHRs raised at Denver's altitude, we hypothesized that early abnormalities in
      pulmonary vascular development contribute to the progression of pulmonary
      hypertension in the FHR. We found that endothelial nitric oxide synthase (eNOS)
      protein content was lower in the lungs of fetal, 1- and 7-day-old, 3-week-old,
      and adult FHRs compared with that in the normal Sprague-Dawley (SDR) and Fischer
      rat strains, all raised at Denver's altitude. In contrast, lung expression of the
      endothelial proteins kinase insert domain-containing receptor/fetal liver kinase
      1 (KDR/Flk-1) and platelet endothelial cell adhesion molecule-1 (CD31) was not
      different between strains. Barium arteriograms showed that pulmonary arterial
      density was reduced in 3-week-old FHRs compared with SDRs. Perinatal treatment of
      FHRs with mild hyperbaria to simulate sea-level alveolar PO(2) improved lung eNOS
      content and pulmonary vascular growth and reduced right ventricular hypertrophy.
      We conclude that the development of pulmonary hypertension in Denver-raised FHRs
      is characterized by reductions in lung eNOS expression and abnormal pulmonary
      vascular growth during the fetal, neonatal, and postnatal periods.

PMID- 10926552
TI  - Expression of N-deacetylase/sulfotransferase and 3-O-sulfotransferase in rat
      alveolar type II cells.
AB  - Basal laminae beneath alveolar type I cells are suggested to contain highly
      sulfated heparan sulfate-containing proteoglycans (PGs), and cultured type II
      cells accumulate highly sulfated matrices. To characterize the regulation of PG
      synthesis during the transition from type II cells to type I cells, we examined
      mRNA expression of N-deacetylase/sulfotransferase (NST) and 3-O-sulfotransferase
      (3-OST), two enzymes specific for heparan sulfate synthesis. We found that both
      freshly isolated and cultured type II cells expressed NST and 3-OST as shown by
      in situ hybridization. Expression of surfactant-associated protein A, B, and C
      mRNAs, determined by semiquantitative PCR, decreased during culture. Expression
      of type I cell marker T1alpha mRNA increased except in cells cultured on an
      Engelbrecht-Holm-Swarm gel. Expression of NST was dependent on cell density and
      matrix and was intense in conditions where cells spread fully, whereas 3-OST
      expression was unchanged in the conditions examined. The PG sulfation inhibitor
      sodium chlorate significantly inhibited cultured type II cell spreading, and this
      inhibition was reversed by sodium sulfate. These results suggest that highly
      sulfated PGs modified by NST are necessary for the spreading of cells during
      transdifferentiation of type II cells to mature type I cells.

PMID- 10926553
TI  - Activation of NF-kappaB induced by H(2)O(2) and TNF-alpha and its effects on ICAM
      1 expression in endothelial cells.
AB  - Reactive oxygen species have been proposed to signal the activation of the
      transcription factor nuclear factor (NF)-kappaB in response to tumor necrosis
      factor (TNF)-alpha challenge. In the present study, we investigated the effects
      of H(2)O(2) and TNF-alpha in mediating activation of NF-kappaB and transcription
      of the intercellular adhesion molecule (ICAM)-1 gene. Northern blot analysis
      showed that TNF-alpha exposure of human dermal microvascular endothelial cells
      (HMEC-1) induced marked increases in ICAM-1 mRNA and cell surface protein
      expression. In contrast, H(2)O(2) added at subcytolytic concentrations failed to
      activate ICAM-1 expression. Challenge with H(2)O(2) also failed to induce NF
      kappaB-driven reporter gene expression in the transduced HMEC-1 cells, whereas
      TNF-alpha increased the NF-kappaB-driven gene expression approximately 10-fold.
      Gel supershift assay revealed the presence of p65 (Rel A), p50, and c-Rel in both
      H(2)O(2)- and TNF-alpha-induced NF-kappaB complexes bound to the ICAM-1 promoter,
      with the binding of the p65 subunit being the most prominent. In vivo
      phosphorylation studies, however, showed that TNF-alpha exposure induced marked
      phosphorylation of NF-kappaB p65 in HMEC-1 cells, whereas H(2)O(2) had no effect.
      These results suggest that reactive oxygen species generation in endothelial
      cells mediates the binding of NF-kappaB to nuclear DNA, whereas TNF-alpha
      generates additional signals that induce phosphorylation of the bound NF-kappaB
      p65 and confer transcriptional competency to NF-kappaB.

PMID- 10926554
TI  - Dexamethasone enhances ras-recision gene expression in cultured murine fetal
      lungs: role in development.
AB  - We have shown that dexamethasone (Dex) accelerates maturation and differentiation
      of cultured fetal murine lungs (Cilley RE, Zgleszewski SE, Krummel TM, and Chinoy
      MR. Surg Forum 47: 692-695, 1996). We now demonstrate that although Dex inhibits
      thinning of acinar walls and secondary septa formation, it does, however, promote
      lung growth. CD-1 murine fetal lungs were cultured for 7 days in the presence and
      absence of 10 nM Dex. Dex-modulated genes were investigated and identified by
      differential display of mRNAs performed with specific anchor primer H-T(11)G and
      24 arbitrary primers. Thirty-five differentially expressed cDNAs were isolated,
      subcloned, sequenced, and identified through BLAST searches. One of these cDNAs,
      termed Dex2, with enhanced expression in Dex-treated lungs, had 100% similarity
      with ras-recision gene (rrg), also known as the lysyl oxidase (LOX) gene that
      encodes lysyl oxidase. LOX gene is very highly conserved, with significant
      sequence similarity among mouse, rat, and human. Two other cDNAs, termed Dex1 and
      Dex4, were also identified as rrg, with 92 and 97% sequence similarity with the
      existing data bank sequence of rrg. LOX enzyme is known to downregulate p21(ras)
      protein and play a central role in the maturation of collagen and elastin in the
      extracellular matrix as well as modulate the cytoskeletal elements. Thus LOX may
      be important in lung developmental processes involving epithelial-mesenchymal
      interactions.

PMID- 10926555
TI  - TNF-alpha increases transcription of Galpha(i-2) in human airway smooth muscle
      cells.
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has an
      important role in the regulation of airway smooth muscle tone and reactivity. We
      have shown previously that TNF-alpha upregulates the expression of Galpha(i-2)
      protein without significantly increasing G(s)alpha protein and enhances adenylyl
      cyclase inhibition by carbachol in cultured human airway smooth muscle cells
      (Hotta K, Emala CW, and Hirshman CA. Am J Physiol Lung Cell Mol Physiol 276: L405
      L411, 1999). The present study was designed to investigate the molecular
      mechanisms by which TNF-alpha upregulates Galpha(i-2) protein in these cells. TNF
      alpha pretreatment for 48 h increased the expression of Galpha(i-2) protein
      without significantly altering the Galpha(i-2) protein half-life (41.0 +/- 8.2 h
      for control and 46.8 +/- 5.2 h for TNF-alpha-treated cells). Inhibition of new
      protein synthesis by cycloheximide blocked the increase in Galpha(i-2) protein
      induced by TNF-alpha. Furthermore, TNF-alpha treatment for 12-24 h increased the
      steady-state level of Galpha(i-2) mRNA without significantly altering Galpha(i-2)
      mRNA half-life (9.0 +/- 0.75 h for control and 8.9 +/- 1.1 h for TNF-alpha
      treated cells). The transcription inhibitor actinomycin D blocked the increase in
      Galpha(i-2) mRNA induced by TNF-alpha. These observations indicate that the
      increase in Galpha(i-2) protein induced by TNF-alpha is due to an increased rate
      of Galpha(i-2) protein synthesis, most likely as a consequence of the
      transcriptional increase in the steady-state levels of its mRNA.

PMID- 10926556
TI  - Quantitative trait locus mapping of genes regulating pulmonary PKC activity and
      PKC-alpha content.
AB  - Strain A/J mice, which are predisposed to experimentally induced asthma and
      adenocarcinoma, have the lowest pulmonary protein kinase (PK) C activity and
      content among 22 inbred mouse strains. PKC in neonatal A/J mice is similar to
      that in other strains, so this difference reflects strain-dependent postnatal
      regulation. PKC activity is 60% higher in C57BL/6J (B6) than in A/J lungs, and
      the protein and mRNA concentrations of PKC-alpha, the major pulmonary PKC
      isozyme, are two- to threefold higher in B6 mice. These differences result from
      more than a single gene as assessed in F(1), F(2), and backcross progeny of B6
      and A/J parents. Quantitative trait locus (QTL) analysis of 23 AxB and BxA
      recombinant inbred strains derived from B6 and A/J progenitors indicates a major
      locus regulating lung PKC-alpha content that maps near the Pkcalpha structural
      gene on chromosome 11 (D11MIT333; likelihood ratio statistic = 12.5) and a major
      locus controlling PKC activity that maps on chromosome 3 (D3MIT19; likelihood
      ratio statistic = 15.4). The chromosome 11 QTL responsible for low PKC-alpha
      content falls within QTLs for susceptibilities to lung tumorigenesis and ozone
      induced toxicity.

PMID- 10926557
TI  - CFTR modulates lung secretory cell proliferation and differentiation.
AB  - We have permanently reversed the lethal phenotype in the cystic fibrosis (CF)
      transmembrane conductance regulator (CFTR)-deficient (knockout) mouse after in
      utero gene therapy with an adenovirus containing the cftr gene. The gene transfer
      targeted somatic stem cells in the developing lung and intestine, and these
      epithelial surfaces demonstrated permanent developmental changes after treatment.
      The survival statistics from the progeny of heterozygote-heterozygote matings
      after in utero cftr gene treatment demonstrated an increased mortality in the
      homozygous normal pups, indicating that overexpression during development was
      detrimental. The lungs of these pups revealed accelerated secretory cell
      proliferation and differentiation. The extent of proliferation and
      differentiation in the secretory cells of the lung parenchyma after in utero
      transfer of the cftr gene was evaluated with morphometric and biochemical
      analyses. These studies provide further support of the regulatory role of the
      cftr gene in the development of the secretory epithelium.

PMID- 10926558
TI  - Determinants of surfactant function in acute lung injury and early recovery.
AB  - Relationships between lung function and surfactant function and composition were
      examined during the evolution of acute lung injury in guinea pigs. Lung mechanics
      and gas exchange were assessed 12, 24, or 48 h after exposure to nebulized
      lipopolysaccharide (LPS). Bronchoalveolar lavage (BAL) fluid was processed for
      phospholipid and protein contents and surfactant protein (SP) A and SP-B levels;
      surfactant function was measured by pulsating bubble surfactometry. Lung
      elastance, tissue resistance, and arterial-alveolar gradient were moderately
      elevated by 12 h after LPS exposure and continued to increase over the first 24 h
      but began to recover between 24 and 48 h. Similarly, the absolute amount of
      30,000 g pelleted SP-A and SP-B, the phospholipid content of BAL fluid, and
      surfactant function declined over the first 24 h after exposure, with recovery
      between 24 and 48 h. BAL fluid total protein content increased steadily over the
      first 48 h after LPS nebulization. In this model of acute lung injury, the intra
      alveolar repletion of surfactant components in early recovery led to improved
      surfactant function despite the presence of potentially inhibitory plasma
      proteins.

PMID- 10926559
TI  - Mice that overexpress Cu/Zn superoxide dismutase are resistant to allergen
      induced changes in airway control.
AB  - Within the respiratory epithelium of asthmatic patients, copper/zinc-containing
      superoxide dismutase (Cu/Zn SOD) is decreased. To address the hypothesis that
      lung Cu/Zn SOD protects against allergen-induced injury, wild-type and transgenic
      mice that overexpress human Cu/Zn SOD were either passively sensitized to
      ovalbumin (OVA) or actively sensitized by repeated airway exposure to OVA.
      Controls included nonsensitized wild-type and transgenic mice given intravenous
      saline or airway exposure to saline. After aerosol challenge to saline or OVA,
      segments of tracheal smooth muscle were obtained for in vitro analysis of neural
      control. In response to electrical field stimulation, wild-type sensitized mice
      challenged with OVA had significant increases in cholinergic reactivity.
      Conversely, sensitized transgenic mice challenged with OVA were resistant to
      changes in neural control. Stimulation of tracheal smooth muscle to elicit
      acetylcholine release showed that passively sensitized wild-type but not
      transgenic mice released more acetylcholine after OVA challenge. Function of the
      M(2) muscarinic autoreceptor was preserved in transgenic mice. These results
      demonstrate that murine airways with elevated Cu/Zn SOD were resistant to
      allergen-induced changes in neural control.

PMID- 10926560
TI  - Role of ras-dependent ERK activation in phorbol ester-induced endothelial cell
      barrier dysfunction.
AB  - The treatment of endothelial cell monolayers with phorbol 12-myristate 13-acetate
      (PMA), a direct protein kinase C (PKC) activator, leads to disruption of
      endothelial cell monolayer integrity and intercellular gap formation. Selective
      inhibition of PKC (with bisindolylmaleimide) and extracellular signal-regulated
      kinases (ERKs; with PD-98059, olomoucine, or ERK antisense oligonucleotides)
      significantly attenuated PMA-induced reductions in transmonolayer electrical
      resistance consistent with PKC- and ERK-mediated endothelial cell barrier
      regulation. An inhibitor of the dual-specificity ERK kinase (MEK), PD-98059,
      completely abolished PMA-induced ERK activation. PMA also produced significant
      time-dependent increases in the activity of Raf-1, a Ser/Thr kinase known to
      activate MEK ( approximately 6-fold increase over basal level). Similarly, PMA
      increased the activity of Ras, which binds and activates Raf-1 ( approximately
      80% increase over basal level). The Ras inhibitor farnesyltransferase inhibitor
      III (100 microM for 3 h) completely abolished PMA-induced Raf-1 activation. Taken
      together, these data suggest that the sequential activation of Ras, Raf-1, and
      MEK are involved in PKC-dependent endothelial cell barrier regulation.

PMID- 10926561
TI  - Expression and regulation of vascular endothelial growth factor in human
      pulmonary epithelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent endothelial cell growth and
      permeability factor highly expressed in rodent alveolar epithelium after injury
      and repair. To investigate VEGF synthesis in human lung epithelial cells, we
      examined VEGF expression by cultured cells under basal conditions and after
      cytokine treatment or oxidative stress. Basal VEGF expression was detected in
      transformed human epithelial cell lines (A549 and 1HAEo-) and in primary human
      bronchial epithelial cells with RT-PCR, Western blot, and immunocytochemistry.
      Among the cytokines tested, only transforming growth factor-beta1 increased the
      levels of excreted VEGF(165) as measured by ELISA. Under hypoxia (0% O(2) for 24
      h), the VEGF(165) level increased fivefold, and this effect was O(2)
      concentration dependent. VEGF concentrations in the medium of all the cell types
      studied reached values similar to those found in bronchoalveolar lavage fluids
      from normal patients. Endothelial cells (human umbilical vein endothelial cells)
      exposed to conditioned medium from primary bronchial epithelial cell cultures
      showed an increased growth rate, which was inhibited in the presence of a
      specific neutralizing antibody to VEGF. These results suggest that lung
      epithelial cells participate in the endothelial repair and angiogenesis that
      follow lung injury through the synthesis of VEGF.

PMID- 10926563
TI  - Dietary glycine blunts lung inflammatory cell influx following acute endotoxin.
AB  - Mortality associated with endotoxin shock is likely mediated by Kupffer cells,
      alveolar macrophages, and circulating neutrophils. Acute dietary glycine prevents
      mortality and blunts increases in serum tumor necrosis factor-alpha (TNF-alpha)
      following endotoxin in rats. Furthermore, acute glycine blunts activation of
      Kupffer cells, alveolar macrophages, and neutrophils by activating a glycine
      gated chloride channel. However, in neuronal tissue, glycine rapidly
      downregulates chloride channel function. Therefore, the long-term effects of a
      glycine-containing diet on survival following endotoxin shock were investigated.
      Dietary glycine for 4 wk improved survival after endotoxin but did not improve
      liver pathology, decrease serum alanine transaminase, or effect TNF-alpha levels
      compared with animals fed control diet. Interestingly, dietary glycine largely
      prevented inflammation and injury in the lung following endotoxin. Surprisingly,
      Kupffer cells from animals fed glycine for 4 wk were no longer inactivated by
      glycine in vitro; however, isolated alveolar macrophages and neutrophils from the
      same animals were sensitive to glycine. These data are consistent with the
      hypothesis that glycine downregulates chloride channels on Kupffer cells but not
      on alveolar macrophages or neutrophils. Importantly, glycine diet for 4 wk
      protected against lung inflammation due to endotoxin. Chronic glycine improves
      survival by unknown mechanisms, but reduction of lung inflammation is likely
      involved.

PMID- 10926562
TI  - Transgenic overexpression of beta(2)-adrenergic receptors in airway epithelial
      cells decreases bronchoconstriction.
AB  - Airway epithelial cells express beta(2)-adrenergic receptors (beta(2)-ARs), but
      their role in regulating airway responsiveness is unclear. With the Clara cell
      secretory protein (CCSP) promoter, we targeted expression of beta(2)-ARs to
      airway epithelium of transgenic (CCSP-beta(2)-AR) mice, thereby mimicking agonist
      activation of receptors only in these cells. In situ hybridization confirmed that
      transgene expression was confined to airway epithelium, and autoradiography
      showed that beta(2)-AR density in CCSP-beta(2)-AR mice was approximately twofold
      that of nontransgenic (NTG) mice. Airway responsiveness measured by whole body
      plethysmography showed that the methacholine dose required to increase enhanced
      pause to 200% of baseline (ED(200)) was greater for CCSP-beta(2)-AR than for NTG
      mice (345 +/- 34 vs. 157 +/- 14 mg/ml; P < 0.01). CCSP-beta(2)-AR mice were also
      less responsive to ozone (0.75 ppm for 4 h) because enhanced pause in NTG mice
      acutely increased to 77% over baseline (P < 0.05) but remained unchanged in the
      CCSP-beta(2)-AR mice. Although both groups were hyperreactive to methacholine 6 h
      after ozone exposure, the ED(200) for ozone-exposed CCSP-beta(2)-AR mice was
      equivalent to that for unexposed NTG mice. These findings show that epithelial
      cell beta(2)-ARs regulate airway responsiveness in vivo and that the
      bronchodilating effect of beta-agonists results from activation of receptors on
      both epithelial and smooth muscle cells.

PMID- 10926564
TI  - Metabolism of phosphatidylglycerol by alveolar macrophages in vitro.
AB  - In whole animal studies, it has been shown that turnover of surfactant
      dipalmitoylphosphatidylglycerol (DPPG) is faster than that of
      dipalmitoylphosphatidylcholine (DPPC). The goal of this investigation was to
      characterize the metabolism of DPPG by alveolar macrophages and to determine
      whether they contribute to the faster alveolar clearance of DPPG. Isolated rat
      alveolar macrophages were incubated with liposomes colabeled with [(3)H]DPPG and
      [(14)C]DPPC. Macrophages internalized both lipids in a time- and temperature
      dependent manner. The uptake of both lipids was increased by surfactant protein
      (SP) A and by adherence of the macrophages to plastic slides. The isotope ratio
      of DPPC to DPPG internalized by macrophages in suspension in the absence of SP-A
      was significantly lower than the isotope ratio in liposomes, suggesting that
      macrophages preferentially internalize DPPG when SP-A is absent. Phospholipase
      activity in macrophage homogenate was higher toward sn-2-labeled DPPG than toward
      sn-2-labeled DPPC. These studies show that alveolar macrophages play an important
      role in catabolizing surfactant lipids and may be partially responsible for the
      relatively faster clearance of DPPG from the lung.

PMID- 10926565
TI  - Free radical production in hypoxic pulmonary artery smooth muscle cells.
AB  - This study used an inexpensive and versatile environmental exposure system to
      test the hypothesis that hypoxia promoted free radical production in primary
      cultures of rat main pulmonary artery smooth muscle cells (PASMCs). Production of
      reactive species was detected by fluorescence microscopy with the probe 2', 7'
      dichlorodihydrofluorescein, which is converted to the fluorescent
      dichlorofluorescein (DCF) in the presence of various oxidants. Flushing the
      airspace above the PASMC cultures with normoxic gas (20% O(2), 75% N(2), and 5%
      CO(2)) resulted in stable PO(2) values of approximately 150 Torr, whereas
      perfusion of the airspace with hypoxic gas (0% O(2), 95% N(2), and 5% CO(2) ) was
      associated with a reduction in PO(2) values to stable levels of approximately 25
      Torr. Hypoxic PASMCs became increasingly fluorescent at approximately 500% above
      the normoxic baseline after 60 min. Hypoxia-induced DCF fluorescence was
      attenuated by the addition of the antioxidants dimethylthiourea and catalase.
      These findings show that PASMCs acutely exposed to hypoxia exhibit a marked
      increase in intracellular DCF fluorescence, suggestive of reactive oxygen or
      nitrogen species production.

PMID- 10926566
TI  - Moving tobacco control beyond "the tipping point".

PMID- 10926567
TI  - Protecting children from passive smoking.

PMID- 10926568
TI  - Improving the treatment of tobacco dependence.

PMID- 10926569
TI  - The Engle verdicts and tobacco litigation.

PMID- 10926570
TI  - The truth about big tobacco in its own words.

PMID- 10926572
TI  - The NHS plan.

PMID- 10926571
TI  - WHO faces up to its tobacco links.

PMID- 10926573
TI  - Tony Blair launches radical NHS plan for England.

PMID- 10926574
TI  - Elderly people will get free nursing care.

PMID- 10926576
TI  - In brief

PMID- 10926575
TI  - Plan leaves england "with third division" health service

PMID- 10926577
TI  - Tobacco companies mounted "dirty tricks" campaign against WHO.

PMID- 10926578
TI  - Smoking in parents increases meningococcal disease risk

PMID- 10926579
TI  - Liz hurley sucks to stop smoking

PMID- 10926580
TI  - Vaccination in utero may cut vertical transmission

PMID- 10926581
TI  - G8 countries accused of ignoring debt relief.

PMID- 10926582
TI  - Drug firms use legal loopholes to safeguard brand names.

PMID- 10926584
TI  - Islet cell transplantation more successful than previously thought

PMID- 10926583
TI  - Surgeon sacked for "misconduct and misjudgment".

PMID- 10926585
TI  - A $145bn verdict and a "roar of moral outrage".

PMID- 10926586
TI  - Smoking, smoking cessation, and lung cancer in the UK since 1950: combination of
      national statistics with two case-control studies.
AB  - OBJECTIVE AND DESIGN: To relate UK national trends since 1950 in smoking, in
      smoking cessation, and in lung cancer to the contrasting results from two large
      case-control studies centred around 1950 and 1990. SETTING: United Kingdom.
      PARTICIPANTS: Hospital patients under 75 years of age with and without lung
      cancer in 1950 and 1990, plus, in 1990, a matched sample of the local population:
      1465 case-control pairs in the 1950 study, and 982 cases plus 3185 controls in
      the 1990 study. MAIN OUTCOME MEASURES: Smoking prevalence and lung cancer.
      RESULTS: For men in early middle age in the United Kingdom the prevalence of
      smoking halved between 1950 and 1990 but the death rate from lung cancer at ages
      35-54 fell even more rapidly, indicating some reduction in the risk among
      continuing smokers. In contrast, women and older men who were still current
      smokers in 1990 were more likely than those in 1950 to have been persistent
      cigarette smokers throughout adult life and so had higher lung cancer rates than
      current smokers in 1950. The cumulative risk of death from lung cancer by age 75
      (in the absence of other causes of death) rose from 6% at 1950 rates to 16% at
      1990 rates in male cigarette smokers, and from 1% to 10% in female cigarette
      smokers. Among both men and women in 1990, however, the former smokers had only a
      fraction of the lung cancer rate of continuing smokers, and this fraction fell
      steeply with time since stopping. By 1990 cessation had almost halved the number
      of lung cancers that would have been expected if the former smokers had
      continued. For men who stopped at ages 60, 50, 40, and 30 the cumulative risks of
      lung cancer by age 75 were 10%, 6%, 3%, and 2%. CONCLUSIONS: People who stop
      smoking, even well into middle age, avoid most of their subsequent risk of lung
      cancer, and stopping before middle age avoids more than 90% of the risk
      attributable to tobacco. Mortality in the near future and throughout the first
      half of the 21st century could be substantially reduced by current smokers giving
      up the habit. In contrast, the extent to which young people henceforth become
      persistent smokers will affect mortality rates chiefly in the middle or second
      half of the 21st century.

PMID- 10926587
TI  - Smoking reduction with oral nicotine inhalers: double blind, randomised clinical
      trial of efficacy and safety.
AB  - OBJECTIVES: To determine whether use of an oral nicotine inhaler can result in
      long term reduction in smoking and whether concomitant use of nicotine
      replacement and smoking is safe. DESIGN: Double blind, randomised, placebo
      controlled trial. Four month trial with a two year follow up. SETTING: Two
      university hospital pulmonary clinics in Switzerland. PARTICIPANTS: 400 healthy
      volunteers, recruited through newspaper advertisements, willing to reduce their
      smoking but unable or unwilling to stop smoking immediately. INTERVENTION: Active
      or placebo inhaler as needed for up to 18 months, with participants encouraged to
      limit their smoking as much as possible. MAIN OUTCOME MEASURES: Number of
      cigarettes smoked per day from week six to end point. Decrease verified by a
      measurement of exhaled carbon monoxide at each time point compared with
      measurement at baseline. RESULTS: At four months sustained reduction of smoking
      was achieved in 52 (26%) participants in the active group and 18 (9%) in the
      placebo group (P<0.001; Fisher's test). Corresponding figures after two years
      were 19 (9.5%) and 6 (3.0%) (P=0.012). CONCLUSION: Nicotine inhalers effectively
      and safely achieved sustained reduction in smoking over 24 months. Reduction with
      or without nicotine substitution may be a feasible first step towards smoking
      cessation in people not able or not willing to stop abruptly.

PMID- 10926588
TI  - Effect of restrictions on smoking at home, at school, and in public places on
      teenage smoking: cross sectional study.
AB  - OBJECTIVE: To determine the relation between extent of restrictions on smoking at
      home, at school, and in public places and smoking uptake and smoking prevalence
      among school students. DESIGN: Cross sectional survey with merged records of
      extent of restrictions on smoking in public places. SETTING: United States.
      PARTICIPANTS: 17 287 high school students. MAIN OUTCOME MEASURES: Five point
      scale of smoking uptake; 30 day smoking prevalence. RESULTS: More restrictive
      arrangements on smoking at home were associated with a greater likelihood of
      being in an earlier stage of smoking uptake (P<0.05) and a lower 30 day
      prevalence (odds ratio 0.79 (95% confidence interval 0.67 to 0.91), P<0.001).
      These findings applied even when parents were smokers. More pervasive
      restrictions on smoking in public places were associated with a higher
      probability of being in a earlier stage of smoking uptake (P<0.05) and lower 30
      day prevalence (0.91 (0.83 to 0.99), P=0.03). School smoking bans were related to
      a greater likelihood of being in an earlier stage of smoking uptake (0.89 (0.85
      to 0.99), P<0.05) and lower prevalence (0. 86 (0.77 to 0.94), P<0.001) only when
      the ban was strongly enforced, as measured by instances when teenagers perceived
      that most or all students obeyed the rule. CONCLUSIONS: These findings suggest
      that restrictions on smoking at home, more extensive bans on smoking in public
      places, and enforced bans on smoking at school may reduce teenage smoking.

PMID- 10926589
TI  - Effect of counselling mothers on their children's exposure to environmental
      tobacco smoke: randomised controlled trial.
AB  - OBJECTIVE: To test the efficacy of behavioural counselling for smoking mothers in
      reducing young children's exposure to environmental tobacco smoke. DESIGN:
      Randomised double blind controlled trial. SETTING: Low income homes in San Diego
      county, California. PARTICIPANTS: 108 ethnically diverse mothers who exposed
      their children (aged <4 years) to tobacco smoke in the home. INTERVENTION:
      Mothers were given seven counselling sessions over three months. MAIN OUTCOME
      MEASURES: Children's reported exposure to environmental tobacco smoke from
      mothers in the home and from all sources; children's cotinine concentrations in
      urine. RESULTS: Mothers' reports of children's exposure to their smoke in the
      home declined in the counselled group from 27.30 cigarettes/week at baseline, to
      4.47 at three months, to 3.66 at 12 months and in the controls from 24.56, to
      12.08, to 8.38. The differences between the groups by time were significant
      (P=0.002). Reported exposure to smoke from all sources showed similar declines,
      with significant differences between groups by time (P=0.008). At 12 months, the
      reported exposure in the counselled group was 41.2% that of controls for mothers'
      smoke (95% confidence interval 34.2% to 48.3%) and was 45.7% (38.4% to 53.0%)
      that of controls for all sources of smoke. Children's mean urine cotinine
      concentrations decreased slightly in the counselled group from 10.93 ng/ml at
      baseline to 10.47 ng/ml at 12 months but increased in the controls from 9.43
      ng/ml to 17.47 ng/ml (differences between groups by time P=0.008). At 12 months
      the cotinine concentration in the counselled group was 55.6% (48.2% to 63.0%)
      that of controls. CONCLUSIONS: Counselling was effective in reducing children's
      exposure to environmental tobacco smoke. Similar counselling in medical and
      social services might protect millions of children from environmental tobacco
      smoke in their homes.

PMID- 10926590
TI  - My cuban experience

PMID- 10926591
TI  - Children's exposure to passive smoking in England since the 1980s: cotinine
      evidence from population surveys.
AB  - OBJECTIVE: To determine whether children's exposure to passive smoking has
      changed since the late 1980s. DESIGN: Cross sectional surveys of nationally
      representative samples of secondary school children carried out between 1988 and
      1998 by Office for National Statistics. SETTING: England. SUBJECTS: Secondary
      school children aged 11-15. MAIN OUTCOME MEASURES: Salivary cotinine
      concentrations in non-smoking children. RESULTS: Cotinine concentrations in all
      non-smoking children almost halved between 1988 and 1998, from a geometric mean
      of 0.96 (95% confidence interval 0.83 to 1.11) ng/ml in 1988 to 0.52 (0.43 to
      0.62) ng/ml in 1998. This reduction was largely due to reductions in exposure in
      children from non-smoking households and to decreases in the percentage of
      parents who smoked. Children living with mothers or fathers who smoked
      experienced little reduction in exposure. CONCLUSIONS: Exposure to passive
      smoking among children in England has approximately halved since the late 1980s.
      This reduction is partly explained by the fall in the percentage of both mothers
      and fathers who smoke and is also likely to reflect reductions of smoking in
      public places. However, there is only limited evidence that children from smoking
      households have experienced a reduction in exposure through parents' avoidance of
      smoking in their presence.

PMID- 10926592
TI  - Decreasing prevalence of cigarette smoking in the middle income country of
      Mauritius: questionnaire survey.
AB  - OBJECTIVES: To describe changes in the prevalence of cigarette smoking in the
      middle income country of Mauritius from 1987 to 1998, and to relate these changes
      to legislative and health promotion efforts over the same period. DESIGN:
      Questionnaire survey. SETTING: Mauritius, an island in the Indian Ocean with a
      population of about 1.2 million (about 70% south Asian, 2% Chinese, and 28%
      Creole). PARTICIPANTS: Data were obtained from 5072 participants in 1987, 6573 in
      1992, and 6281 in 1998. MAIN OUTCOME MEASURES: Prevalence of current smoking in
      1987, 1992, and 1998, sales of cigarettes in Mauritius, and information on
      activities for control of tobacco. RESULTS: Self reported cigarette smoking has
      been decreasing in Mauritius since 1987, with the largest decrease between 1987
      and 1992. From 1987 to 1998 smoking prevalence decreased by 23% in men and 61% in
      women. Smoking decreased across all age and ethnic groups and across different
      levels of income and education. Sales of cigarettes also decreased in line with
      smoking prevalence. CONCLUSIONS: The introduction of cigarette taxes, a limited
      health promotion programme, and the absence of massive promotional campaigns by
      the sole tobacco company on Mauritius have led to a striking and continued
      decrease in smoking prevalence and cigarette consumption on the island.

PMID- 10926593
TI  - Increased mortality among Danish women: population based register study.

PMID- 10926594
TI  - In favour of the weed

PMID- 10926596
TI  - Targeting the kids

PMID- 10926595
TI  - Impact of the Massachusetts tobacco control programme: population based trend
      analysis.
AB  - OBJECTIVE: To assess the impact of the Massachusetts tobacco control programme,
      which, since its start in January 1993, has spent over $200m-"the highest per
      capita expenditure for tobacco control in the world"-funded by an extra tax of 25
      cents per pack of cigarettes. DESIGN: Population based trend analysis with
      comparison group. SUBJECTS: Adult residents of Massachusetts and other US states
      excluding California. MAIN OUTCOME MEASURES: Per capita consumption of cigarettes
      as measured by states' sales tax records; prevalence of smoking in adults as
      measured by several population-based telephone surveys. RESULTS: From 1988 to
      1992, decline in per capita consumption of cigarettes in Massachusetts (15%) was
      similar to that in the comparison states (14%), corresponding to an annual
      decline of 3-4% for both groups. During 1992-3, consumption continued to decline
      by 4% in the comparison states but dropped 12% in Massachusetts in response to
      the tax increase. From 1993 onward, consumption in Massachusetts showed a
      consistent annual decline of more than 4%, whereas in the comparison states it
      levelled off, decreasing by less than 1% a year. From 1992, the prevalence of
      adult smoking in Massachusetts has declined annually by 0.43% (95% confidence
      interval 0.21% to 0.66%) compared with an increase of 0. 03% (-0.06% to 0.12%) in
      the comparison states (P<0.001). CONCLUSIONS: These findings show that a strongly
      implemented, comprehensive tobacco control programme can significantly reduce
      tobacco use.

PMID- 10926597
TI  - Effectiveness of interventions to help people stop smoking: findings from the
      Cochrane Library.

PMID- 10926598
TI  - The economics of global tobacco control.

PMID- 10926599
TI  - Everest and the therapeutic cigarette

PMID- 10926600
TI  - Do candy cigarettes encourage young people to smoke?

PMID- 10926601
TI  - A day in the life of an advertising man: review of internal documents from the UK
      tobacco industry's principal advertising agencies.

PMID- 10926602
TI  - "Operation Berkshire": the international tobacco companies' conspiracy.

PMID- 10926603
TI  - Religious challenge by shareholder actions: changing the behaviour of tobacco
      companies and their allies.

PMID- 10926605
TI  - Smoking in british popular culture 1800-2000

PMID- 10926604
TI  - Obituaries

PMID- 10926606
TI  - Denial & delay: the political history of smoking and health 1951-1964,
      scientists, government and industry as seen in the papers at the public records
      office

PMID- 10926607
TI  - Blood and smoke

PMID- 10926608
TI  - Stopping smoking

PMID- 10926610
TI  - Is general practice being consigned to history?

PMID- 10926609
TI  - Bookcase

PMID- 10926612
TI  - Widespread smoking cessation has halved UK lung cancer mortality

PMID- 10926611
TI  - Happy birthday, Ma'am

PMID- 10926614
TI  - Smoking bans at home and in public places cut teenage smoking

PMID- 10926613
TI  - Smoking reduction can help the recalcitrant smoker

PMID- 10926615
TI  - Counselling smoking mothers protects their children from passive smoking

PMID- 10926616
TI  - Parents who smoke are still exposing their children to passive smoking in the
      home

PMID- 10926617
TI  - Tobacco control is successful in mauritius

PMID- 10926618
TI  - Medical officer in the royal naval reserve

PMID- 10926619
TI  - Controversies in physiology

PMID- 10926620
TI  - Opposing views on the alveolar surface, alveolar models, and the role of
      surfactant.

PMID- 10926621
TI  - A new ventilator for monitoring lung mechanics in small animals.
AB  - Researchers investigating the genetic component of various disease states rely
      increasingly on murine models. We have developed a ventilator to simplify
      respiratory research in small animals down to murine size. The new ventilator
      provides constant-flow inflation and tidal volume delivery independent of
      respiratory parameter changes. The inclusion of end-inspiratory and end
      expiratory pauses simplifies the measurement of airway resistance and compliance
      and allows the detection of dynamic hyperinflation (auto-positive end-expiratory
      pressure). After bench testing, we performed intravenous methacholine challenge
      on two strains of mice (A/J and C57bl/bj) known to differ in their responses by
      using the new ventilator. Dynamic hyperinflation and a decrease in compliance
      developed during methacholine challenge whenever respiratory rates of 60-120
      breaths/min were employed. In contrast, if dynamic hyperinflation was prevented
      by lengthening expiratory time, (respiratory rate = 20 breaths/min), static
      compliance remained constant. More importantly, the coefficient of variation of
      the results decreased when lung volume shifts were prevented. In conclusion,
      airway challenge studies have greater precision when dynamic hyperinflation is
      prevented.

PMID- 10926622
TI  - Myogenic and scalp signals evoked by midinspiratory airway occlusion.
AB  - A somatosensory potential that is evoked by transient added inspiratory load has
      previously been described (Davenport PW, Friedman WA, Thompson FJ, and Franzen O.
      J Appl Physiol 60: 1843-1848, 1986). This evoked potential is novel because it
      arises in response to a stimulus that also evokes a muscle response, and so this
      potential could contain myogenic components. The present study was undertaken to
      define the relationship between the scalp response and other physiological
      responses that are evoked by airway occlusion. Evoked signals were recorded from
      the scalp, scalenus anterior, masseter, and electrooculogram. Responses to a 200
      ms midinspiratory occlusion were recorded in 12 healthy volunteers. Evoked
      responses were reliably recorded at C(3)-C(Z) and C(4)-C(Z) and from the skin
      overlying the scalenus anterior in 11 of these subjects. The onset latencies were
      15.7 +/- 3.1 at C(3)-C(Z), 15.9 +/- 2.1 at C(4)-C(Z), and 17.6 +/- 5.5 ms at
      scalenus anterior. In nine subjects, the masseter response appeared to coincide
      with the mouth pressure trace, and this was interpreted as movement artifact. No
      consistent electrooculogram or frontal electroencephalogram response was
      recorded. Because of the similarity in onset latency at C(3)-C(Z), C(4)-C(Z), and
      scalenus anterior, it was concluded that the myogenic signal may contribute to
      the scalp response and should be viewed as a potential source of artifact in
      experiments of this nature.

PMID- 10926624
TI  - Differential cardiorespiratory control elicited by activation of ventral
      medullary sites in mice.
AB  - We studied the respiratory and blood pressure responses to chemical stimulation
      of two regions of the ventral brainstem in mice: the rostral and caudal
      ventrolateral medulla (RVLM and CVLM, respectively). Stimulation of the RVLM by
      microinjections of the excitatory amino acid L-glutamate induced increases in
      diaphragm activity and breathing frequency, elevation of blood pressure (BP), and
      a slight increase in heart rate (HR). However, activation of the CVLM induced a
      decrease in breathing frequency, mainly due to prolongation of expiratory time
      (TE), and hypotension associated with a slight slowing of HR. Because adrenergic
      mechanisms are known to participate in the control of respiratory timing, we
      examined the role of alpha(2)-adrenergic receptors in the RVLM region in
      mediating these inhibitory effects. The findings demonstrated that blockade of
      the alpha(2)-adrenergic receptors within the RVLM by prior microinjection of SKF
      86466 (an alpha(2)-adrenergic receptor blocker) significantly reduced changes in
      TE induced by CVLM stimulation but had little effect on BP responses. These
      results indicate that, in mice, activation of the RVLM increases respiratory
      drive associated with an elevation of BP, but stimulation of CVLM induces
      prolongation of TE via an alpha(2)-adrenergic signal transduction pathway.

PMID- 10926623
TI  - Effects of short-term oral salbutamol administration on exercise endurance and
      metabolism.
AB  - The present study examined whether oral short-term administration of salbutamol
      (Sal) modifies performance and selected hormonal and metabolic variables during
      submaximal exercise. Eight recreational male athletes completed two cycling
      trials at 80-85% peak O(2) consumption until exhaustion after either gelatin
      placebo (Pla) or oral Sal (12 mg/day for 3 wk) treatment, according to a double
      blind and randomized protocol. Blood samples were collected at rest, after 5, 10,
      and 15 min, and at exhaustion to determine growth hormone (GH), cortisol,
      testosterone, triiodothyronine (T(3)), C peptide, free fatty acid (FFA), blood
      glucose, lactate, and blood urea values. Time of cycling was significantly
      increased after chronic Sal intake (Sal: 30.5 +/- 3.1 vs. Pla: 23.7 +/- 1.6 min,
      P < 0.05). No change in any variable was found before cycling except a decrease
      in blood urea concentration and an increase in T(3) after Sal that remained
      significant throughout the exercise test (P < 0.05). Compared with rest, exercise
      resulted in a significant increase in GH, cortisol, testosterone, T(3), FFAs, and
      lactate and a decrease in C peptide after both treatments with higher exercise
      FFA levels and exhaustion GH concentrations after Sal (P < 0.05). Sal but not Pla
      significantly decreased exercise blood glucose levels. From these data, short
      term Sal intake did appear to improve performance during intense submaximal
      exercise with concomitant increase in substrate availability and utilization, but
      the exact mechanisms involved need further investigation.

PMID- 10926625
TI  - Effects of inertial load and countermeasures on the distribution of pulmonary
      blood flow.
AB  - We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the
      countermeasures of anti-G suit and positive pressure breathing during G (PBG),
      specifically during +G(z), on regional pulmonary blood flow distribution.
      Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z),
      and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force
      Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force
      of the Earth, that is, the dorsal-to-ventral inertial force, was present for all
      runs). Fluorescent microspheres were injected into the pulmonary vasculature as a
      marker of regional pulmonary blood flow. Lungs were excised, dried, and diced
      into approximately 2-cm(3) pieces, and the fluorescence of each piece was
      measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from
      cranial and hilar regions toward caudal and peripheral regions of the lung. This
      redistribution shifted back toward cranial and hilar regions as anti-G suit
      inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased
      with +G(z) stress and decreased at the higher anti-G suit pressures. The
      distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated
      anatomic structure as the major determinant of pulmonary blood flow.

PMID- 10926626
TI  - Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial
      infarction.
AB  - To investigate the secretion of the plasma levels of atrial natriuretic peptide
      (ANP) in patients with acute myocardial infarction (AMI), we evaluated the
      relationship between plasma levels of ANP and pulmonary capillary wedge pressure
      (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately
      12 h after the attack) (group 1) and compared data with those obtained after 1 mo
      (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated
      with PCWP. The slope of the linear regression line between the PCWP and ANP in
      group 1 was significantly lower, by about one-third, than that in group 2. In
      addition, we examined changes in ANP levels and left ventricular end-diastolic
      pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into
      the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after
      AMI were significantly higher than those before; however, despite the persistent
      high LVEDP during the 180 min after AMI, ANP levels decreased gradually and
      significantly to 63% of the peak level at 150 min. These findings suggest that
      the secretion of ANP during the acute phase of myocardial infarction may be
      insufficient relative to the chronic phase.

PMID- 10926627
TI  - Estimation of skeletal muscle mass by bioelectrical impedance analysis.
AB  - The purpose of this study was to develop and cross-validate predictive equations
      for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis
      (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared
      with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86
      yr, at two different laboratories. Within each laboratory, equations for
      predicting SM mass from BIA measurements were derived using the data of the
      Caucasian subjects. These equations were then applied to the Caucasian subjects
      from the other laboratory to cross-validate the BIA method. Because the equations
      cross-validated (i.e., were not different), the data from both laboratories were
      pooled to generate the final regression equation SM mass (kg) = [(Ht<SUP>2</SUP>/
      <IT>R</IT> x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is
      height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women
      = 0; and age is in years. The r(2) and SE of estimate of the regression equation
      were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was
      applicable to Hispanics and African-Americans, but it underestimated SM mass in
      Asians. These results suggest that the BIA equation provides valid estimates of
      SM mass in healthy adults varying in age and adiposity.

PMID- 10926628
TI  - Influence of cholesterol status on blood lipid and lipoprotein enzyme responses
      to aerobic exercise.
AB  - To compare postexercise changes in plasma lipids and lipoprotein enzymes in 13
      hypercholesterolemic (HC) and 12 normocholesterolemic men [total cholesterol (TC)
      252 +/- 5 vs. 179 +/- 5 mg/dl], fasting blood samples were obtained 24 h before,
      immediately, 24, and 48 h after a single bout of treadmill walking (70% peak O(2)
      consumption, 500 kcal expenditure). Significant findings (P < 0.05 for all) for
      plasma volume-adjusted lipid and enzyme variables were that TC, low-density
      lipoprotein cholesterol, and cholesterol ester transfer protein activity were
      higher in the HC group but did not influence the lipid responses to exercise.
      Across groups, TC was transiently reduced immediately after exercise but returned
      to baseline levels by 24 h postexercise. Decreases in triglyceride and increases
      in high-density-lipoprotein cholesterol (HDL-C) and HDL(3)-C were observed 24 h
      after exercise and lasted through 48 h. Lipoprotein lipase activity was elevated
      by 24 h and remained elevated 48 h after exercise. HDL(2)-C, cholesterol ester
      transfer protein activity, hepatic triglyceride lipase, and lecithin: cholesterol
      acyltransferase activities did not change after exercise. These data indicate
      that the exercise-induced changes in HDL-C and triglyceride are similar in HC and
      normocholesterolemic men and may be mediated, at least in part, by an increase in
      lipoprotein lipase activity.

PMID- 10926629
TI  - Effects of inspiratory flow on diaphragmatic motor output in normal subjects.
AB  - Increasing inspiratory flow (V) has been shown to shorten neural inspiratory time
      (TI(n)) in normal subjects breathing on a mechanical ventilator, but the effect
      of V on respiratory motor output before inspiratory termination has not
      previously been studied in humans. While breathing spontaneously on a mechanical
      ventilator, eight normal subjects were intermittently exposed to 200-ms-duration
      positive pressure pulses of different amplitudes at the onset of inspiration.
      Based on the increase in V above control breaths (DeltaV), trials were grouped
      into small, medium, and large groups (mean DeltaV: 0.51, 1.11, and 1.65 l/s,
      respectively). We measured TI(n), transdiaphragmatic pressure (Pdi), and
      electrical activity (electromyogram) of the diaphragm (EMGdi). Transient
      increases in V caused shortening of TI(n) from 1.34 to 1.10 (not significant),
      1.55 to 1.11 (P < 0.005), and 1.58 to 1.17 s (P < 0. 005) in the small, medium,
      and large DeltaV groups, respectively. EMGdi measured at end TI(n) of the pulse
      breaths was 131 (P < 0.05), 142, and 155% (P < 0.05) of the EMGdi of the control
      breaths at an identical time point in the small, medium, and large trials,
      respectively. The latency of the excitation was 126 +/- 42 (SD) ms, consistent
      with a reflex effect. Increasing V had two countervailing effects on Pdi: 1) a
      depressant mechanical effect due primarily to the force-length (11.2 cmH(2)O/l)
      relation of the diaphragm, and 2) an increase in diaphragm activation. For the
      eight subjects, mean peak Pdi did not change significantly, but there was
      significant intersubject variability, reflecting variability in the strength of
      the excitation reflex. We conclude that increasing inspiratory V causes a graded
      facilitation of EMGdi, which serves to counteract the negative effect of the
      force-length relation on Pdi.

PMID- 10926630
TI  - Increased vasoconstrictor sensitivity in obstructive sleep apnea.
AB  - We studied vasoconstrictor sensitivity and cholinergic responsiveness of the
      forearm vasculature in 10 male patients with obstructive sleep apnea (OSA) and 10
      healthy controls. Subjects with regular medication, known arterial hypertension,
      diabetes mellitus, or dyslipidemia were not included in this study. Age, body
      mass index, blood pressure, blood glucose, serum lipids, and baseline forearm
      vascular conductance (derived from venous occlusion plethysmography and intra
      arterial blood pressure measurement) did not differ significantly between these
      two groups. With use of three dosage steps each, angiotensin II and acetylcholine
      were successively infused into the brachial artery. During infusion of
      angiotensin II, mean conductance was 39.6% lower (P = 0.002) in the OSA patients
      compared with that in the control subjects. Vascular responsiveness to increasing
      dosages of acetylcholine was not significantly altered in the OSA group. These
      findings suggest an enhanced vasoconstrictor sensitivity in the forearm
      vasculature in OSA. The hypothesis that endothelial function in OSA is impaired
      independently of other cardiovascular risk factors is not supported by the
      present results.

PMID- 10926631
TI  - Hemodynamic effects of 15-microm-diameter microspheres on the rat pulmonary
      circulation.
AB  - The microsphere method has been used extensively to measure regional blood flow
      in large laboratory animals. A fundamental premise of the method is that
      microspheres do not alter regional flow or vascular tone. Whereas this assumption
      is accepted in large animals, it may not be valid in the pulmonary circulation of
      smaller animals. Three studies were performed to determine the hemodynamic
      effects of microspheres on the rat pulmonary circulation. Increasing numbers of
      15-microm-diameter microspheres were injected into a fully dilated, isolated-lung
      preparation. Vascular resistance increased 0.8% for every 100,000 microspheres
      injected. Microspheres were also injected into an isolated-lung preparation in
      which vascular tone was increased with hypoxia. Microspheres did not induce
      vasodilatation, as reported in other vascular beds. Fluorescent microspheres were
      injected via tail veins into awake rats, and the spatial locations of the
      microspheres were determined. Regional distributions remained highly correlated
      when microspheres of one color were injected after microspheres of another color.
      This indicates that the initial injection did not alter regional perfusion. We
      conclude that, when used in appropriate numbers, 15-microm-diameter microspheres
      do not alter regional flow or vascular tone in the rat pulmonary circulation.

PMID- 10926632
TI  - Mechanism of reduced maximal expiratory flow with aging.
AB  - To investigate the determinants of maximal expiratory flow (MEF) with aging, 17
      younger (7 men and 10 women, 39 +/- 4 yr, mean +/- SD) and 19 older (11 men and 8
      women, 69 +/- 3 yr) subjects with normal pulmonary function were studied. For
      further comparison, we also studied 10 middle-aged men with normal lung function
      (54 +/- 6 yr) and 15 middle-aged men (54 +/- 7 yr) with mild chronic airflow
      limitation (CAL; i.e., forced expiratory volume in 1 s/forced vital capacity = 63
      +/- 8%). MEF, static lung elastic recoil pressure (Pst), and the minimal pressure
      for maximal flow (Pcrit) were determined in a pressure-compensated, volume
      displacement body plethysmograph. Values were compared at 60, 70, and 80% of
      total lung capacity. In the older subjects, decreases in MEF (P < 0.01) and Pcrit
      (P < 0.05), compared with the younger subjects, were explained mainly by loss of
      Pst (P < 0.05). In the CAL subjects, MEF and Pcrit were lower (P < 0.05) than in
      the older subjects, but Pst was similar. Thus decreases in MEF and Pcrit were
      greater than could be explained by the loss of Pst and appeared to be related to
      increased upstream resistance. These data indicate that the loss of lung recoil
      explains the decrease in MEF with aging subjects, but not in the mild CAL
      patients that we studied.

PMID- 10926633
TI  - Treadmill economy in girls and women matched for height and weight.
AB  - We investigated differences in walking (80 m/min) and running (147 m/min) economy
      [submaximal oxygen consumption (VO(2) (submax))] between adolescent girls (n =
      13; age = 13.3 +/- 0.9 yr) and young women (n = 23; age = 21.0 +/- 1.5 yr).
      Subjects were matched for height (158.7 +/- 2.9 cm) and weight (52.1 +/- 3.0 kg).
      Anthropometric measures (height, weight, breadths, skinfolds) and preexercise
      oxygen consumption were obtained on all subjects before submaximal and maximal
      treadmill exercise. Anthropometric measures were similar between groups, as was
      maximal oxygen consumption (girls, 47.7 +/- 5.2; women, 47.5 +/- 5.7 ml. kg(-1).
      min(-1)). VO(2) (submax) was significantly greater (P < 0.0002) in girls compared
      with women during both walking (16.4 +/- 1.7 vs. 14.4 +/- 1. 1 ml. kg(-1). min(
      1)) and running (38.1 +/- 3.7 vs. 33.9 +/- 2.4 ml. kg(-1). min(-1)). Preexercise
      oxygen consumption (4.4 vs. 3.9 ml. kg(-1). min(-1)) accounted for only a
      fraction of the differences found in exercise economy. Although heart rate and
      respiratory frequency were greater in the girls in both walking (118 +/- 11 vs.
      104 +/- 12 beats/min and 31 +/- 3 vs. 25 +/- 4 breaths/min, respectively; P <
      0.002) and running (180 +/- 15 vs. 163 +/- 17 beats/min and 47 +/- 11 vs. 38 +/-
      8 breaths/min; P < 0.005), this did not likely account for a large part of the
      difference in VO(2) (submax) between groups.

PMID- 10926634
TI  - Effects of high myoplasmic L-lactate concentration on E-C coupling in mammalian
      skeletal muscle.
AB  - The effects of high myoplasmic L-lactate concentrations (20-40 mM) at constant pH
      (7.1) were investigated on contractile protein function, voltage-dependent Ca(2+)
      release, and passive Ca(2+) leak from the sarcoplasmic reticulum (SR) in
      mechanically skinned fast-twitch (extensor digitorum longus; EDL) and slow-twitch
      (soleus) fibers of the rat. L-Lactate (20 mM) significantly reduced maximum
      Ca(2+)-activated force by 4 +/- 0.5% (n = 5, P < 0.05) and 5 +/- 0.4% (n = 6, P <
      0.05) for EDL and soleus, respectively. The Ca(2+) sensitivity was also
      significantly decreased by 0.06 +/- 0. 002 (n = 5, P < 0.05) and 0.13 +/- 0.01 (n
      = 6, P < 0.001) pCa units, respectively. Exposure to L-lactate (20 mM) for 30 s
      reduced depolarization-induced force responses by ChCl substitution by 7 +/- 3%
      (n = 17, P < 0.05). This inhibition was not obviously affected by the presence of
      the lactate transport blocker quercetin (10 microM), or the chloride channel
      blocker anthracene-9-carboxylic acid (100 microM). L-Lactate (20 mM) increased
      passive Ca(2+) leak from the SR in EDL fibers (the integral of the response to
      caffeine was reduced by 16 +/- 5%, n = 9, P < 0.05) with no apparent effect in
      soleus fibers (100 +/- 2%, n = 3). These results indicate that the L-lactate ion
      per se has negligible effects on either voltage-dependent Ca(2+) release or SR
      Ca(2+) handling and exerts only a modest inhibitory effect on muscle
      contractility at the level of the contractile proteins.

PMID- 10926635
TI  - Role of K(ATP)(+) channels and adenosine in the control of coronary blood flow
      during exercise.
AB  - The present study was designed to examine the role of ATP-sensitive potassium
      (K(ATP)(+)) channels during exercise and to test the hypothesis that adenosine
      increases to compensate for the loss of K(ATP)(+) channel function and adenosine
      inhibition produced by glibenclamide. Graded treadmill exercise was used to
      increase myocardial O(2) consumption in dogs before and during K(ATP)(+) channel
      blockade with glibenclamide (1 mg/kg iv), which also blocks adenosine mediated
      coronary vasodilation. Cardiac interstitial adenosine concentration was estimated
      from arterial and coronary venous values by using a previously tested
      mathematical model (Kroll K and Stepp DW. Am J Physiol Heart Circ Physiol 270:
      H1469-H1483, 1996). Coronary venous O(2) tension was used as an index of the
      balance between O(2) delivery and myocardial O(2) consumption. During control
      exercise, myocardial O(2) consumption increased approximately 4-fold, and
      coronary venous O(2) tension fell from 19 to 14 Torr. After K(ATP)(+) channel
      blockade, coronary venous O(2) tension was decreased below control vehicle values
      at rest and during exercise. However, during exercise with glibenclamide, the
      slope of the line of coronary venous O(2) tension vs. myocardial O(2) consumption
      was the same as during control exercise. Estimated interstitial adenosine
      concentration with glibenclamide was not different from control vehicle and was
      well below the level necessary to overcome the 10-fold shift in the adenosine
      dose-response curve due to glibenclamide. In conclusion, K(ATP)(+) channel
      blockade decreases the balance between resting coronary O(2) delivery and
      myocardial O(2) consumption, but K(ATP)(+) channels are not required for the
      increase in coronary blood flow during exercise. Furthermore, interstitial
      adenosine concentration does not increase to compensate for the loss of K(ATP)(+)
      channel function.

PMID- 10926636
TI  - Hemodynamic effects of pressures applied to the upper airway during sleep.
AB  - The increase in systemic blood pressure after an obstructive apnea is due, in
      part, to sympathetically mediated vasoconstriction. We questioned whether upper
      airway (UA) receptors could contribute reflexly to this vasoconstriction. Four
      unanesthetized dogs were studied during wakefulness and non-rapid-eye-movement
      (NREM) sleep. The dogs breathed via a fenestrated tracheostomy tube sealed around
      the tracheal stoma. The snout was sealed with an airtight mask, thereby isolating
      the UA when the fenestration was closed and exposing the UA to negative
      inspiratory intrathoracic pressure when it was open. The blood pressure response
      to three UA perturbations was studied: 1) square-wave negative pressures
      sufficient to cause UA collapse with the fenestration closed during a mechanical
      hyperventilation-induced central apnea; 2) tracheal occlusion with the
      fenestration open vs. closed; and 3) high-frequency pressure oscillations (HFPO)
      with the fenestration closed. During NREM sleep, 1) blood pressure response to
      tracheal occlusion was similar with the fenestration open or closed; 2)
      collapsing the UA with negative pressures failed to alter blood pressure during a
      central apnea; and 3) application of HFPO to the UA during eupnea and resistive
      loaded breaths increased heart rate and blood pressure. However, these changes
      were likely to be secondary to the effects of HFPO-induced reflex changes on
      prolonging expiratory time. These findings suggest that activation of UA pressure
      sensitive receptors does not contribute directly to the pressor response
      associated with sleep-disordered breathing events.

PMID- 10926637
TI  - Pyruvate ingestion for 7 days does not improve aerobic performance in well
      trained individuals.
AB  - The purposes of the present studies were to test the hypotheses that lower
      dosages of oral pyruvate ingestion would increase blood pyruvate concentration
      and that the ingestion of a commonly recommended dosage of pyruvate (7 g) for 7
      days would enhance performance during intense aerobic exercise in well-trained
      individuals. Nine recreationally active subjects (8 women, 1 man) consumed 7, 15,
      and 25 g of pyruvate and were monitored for a 4-h period to determine whether
      blood metabolites were altered. Pyruvate consumption failed to significantly
      elevate blood pyruvate, and it had no effect on indexes of carbohydrate (blood
      glucose, lactate) or lipid metabolism (blood glycerol, plasma free fatty acids).
      As a follow-up, we administered 7 g/day of either placebo or pyruvate, for a 1-wk
      period to seven, well-trained male cyclists (maximal oxygen consumption, 62.3 +/-
      3.0 ml. kg(-1). min(-1)) in a randomized, double-blind, crossover trial. Subjects
      cycled at 74-80% of their maximal oxygen consumption until exhaustion. There was
      no difference in performance times between the two trials (placebo, 91 +/- 9 min;
      pyruvate, 88 +/- 8 min). Measured blood parameters (insulin, peptide C, glucose,
      lactate, glycerol, free fatty acids) were also unaffected. Our results indicate
      that oral pyruvate supplementation does not increase blood pyruvate content and
      does not enhance performance during intense exercise in well-trained cyclists.

PMID- 10926638
TI  - Strength loss after eccentric contractions is unaffected by creatine
      supplementation.
AB  - This study's objective was to determine whether 14 days of dietary creatine
      supplementation preceding an injurious bout of eccentric contractions affect the
      in vivo strength loss of mouse anterior crural muscles. Three groups of nine mice
      each were fed a meal diet for 14 days, one group at each of three levels of
      creatine supplementation (i.e., 0, 0.5, and 1% creatine). Electrically stimulated
      concentric, isometric, and eccentric contraction torques produced about the ankle
      were measured both before and after a bout of 150 eccentric contractions.
      Tibialis anterior muscle creatine concentration was significantly increased by
      the supplementation, being 12% higher in the mice fed the 1% creatine diet
      compared with control mice. After the bout of eccentric contractions, the
      reductions in torque (i.e., 46-58%) were similar for the isometric contraction,
      all eccentric contractions, and the slow (i.e., </=200 (o)/s) concentric
      contractions; above 200 (o)/s, the percent reduction in concentric torque
      increased progressively to 85-88% at 1,000-1,200 (o)/s. However, there was no
      effect of creatine supplementation on the isometric torque loss or on the torque
      loss at any eccentric or concentric angular velocity (P >/= 0.62). In conclusion,
      a moderate increase in muscle creatine concentration induced by dietary
      supplementation in mice does not affect the strength loss after eccentric
      contractions.

PMID- 10926639
TI  - Phrenic motoneuron morphology during rapid diaphragm muscle growth.
AB  - In the adult rat, there is a general correspondence between the sizes of
      motoneurons, motor units, and muscle fibers that has particular functional
      importance in motor control. During early postnatal development, after the
      establishment of singular innervation, there is rapid growth of diaphragm muscle
      (Dia(m)) fibers. In the present study, the association between Dia(m) fiber
      growth and changes in phrenic motoneuron size (both somal and dendritic) was
      evaluated from postnatal day 21 (D21) to adulthood. Phrenic motoneurons were
      retrogradely labeled with fluorescent tetramethylrhodamine dextran (3,000 MW),
      and motoneuron somal volumes and surface areas were measured using three
      dimensional confocal microscopy. In separate animals, phrenic motoneurons
      retrogradely labeled with choleratoxin B-fragment were visualized using
      immunocytochemistry, and dendritic arborization was analyzed by camera lucida.
      Between D21 and adulthood, Dia(m) fiber cross-sectional area increased by
      approximately 164% overall, with the growth of type II fibers being
      disproportionate to that of type I fibers. There was also substantial growth of
      phrenic motoneurons ( approximately 360% increase in total surface area), during
      this same period, that was primarily attributable to an expansion of dendritic
      surface area. Comparison of the distribution of phrenic motoneuron surface areas
      between D21 and adults suggests the establishment of a bimodal distribution that
      may have functional significance for motor unit recruitment in the adult rat.

PMID- 10926640
TI  - Duodenal vs. gastric administration of labeled leucine for the study of
      splanchnic metabolism in humans.
AB  - Low-rate (6 ml/h) intragastric infusion of stable, isotope-labeled amino acids is
      commonly used to assess the splanchnic handling of amino acids in humans.
      However, when used in the postabsorptive state, this method yields unreliable
      plasma isotopic enrichments, with a coefficient of variation >10%. In this
      metabolic condition, we confirmed in six subjects that an intragastric infusion
      of L-[(2)H(3)]leucine at 6 ml/h yields an unreliable isotopic steady state in
      plasma amino acids with a coefficient of variation of 43 +/- 12% (mean +/- SD).
      In five additional subjects, we assessed the effects of 1) increasing the rate of
      delivery of a leucine tracer in an isotonic plasmalike solution at 240 ml/h into
      the gastric site, and 2) changing the site of infusion from gastric to duodenal
      with this same high rate of delivery. In contrast to the gastric route, and
      regardless of the rate of delivery, only the intraduodenal route allowed 1)
      isotopic plasma steady state (i.e., coefficients of variation were <10%: 5 +/-
      3%), and 2) reproducible leucine extraction coefficients (22 +/- 5%). We conclude
      that an infusion site that bypasses the gastric emptying process, i.e., the
      duodenal route, along with delivery of a plasmalike solution, is necessary to
      reach isotopic steady state in plasma when labeled leucine is infused into the
      gastrointestinal tract in the postabsorptive state.

PMID- 10926641
TI  - Response-time enhancement of a clinical gas analyzer facilitates measurement of
      breath-by-breath gas exchange.
AB  - Tidal ventilation gas-exchange models in respiratory physiology and medicine not
      only require solution of mass balance equations breath-by-breath but also may
      require within-breath measurements, which are instantaneous functions of time.
      This demands a degree of temporal resolution and fidelity of integration of gas
      flow and concentration signals that cannot be provided by most clinical gas
      analyzers because of their slow response times. We have characterized the step
      responses of the Datex Ultima (Datex Instrumentation, Helsinki, Finland) gas
      analyzer to oxygen, carbon dioxide, and nitrous oxide in terms of a Gompertz four
      parameter sigmoidal function. By inversion of this function, we were able to
      reduce the rise times for all these gases almost fivefold, and, by its
      application to real on-line respiratory gas signals, it is possible to achieve a
      performance comparable to the fastest mass spectrometers. With the use of this
      technique, measurements required for non-steady-state and tidal gas-exchange
      models can be made easily and reliably in the clinical setting.

PMID- 10926642
TI  - Influence of posture and breathing route on neural drive to upper airway dilator
      muscles during exercise.
AB  - Our purpose was to determine the influence of posture and breathing route on
      electromyographic (EMG) activities of nasal dilator (NDM) and genioglossus (GG)
      muscles during exercise. Nasal and oral airflow rates and EMG activities of the
      NDM and GG were recorded in 10 subjects at rest and during upright and supine
      incremental cycling exercise to exhaustion. EMG activities immediately before and
      after the switch from nasal to oronasal breathing were also determined for those
      subjects who demonstrated a clear switch point (n = 7). NDM and GG EMG activities
      were significantly correlated with increases in nasal, oral, and total
      ventilatory rates during exercise, and these relationships were not altered by
      posture. In both upright and supine exercise, NDM activity rose more sharply as a
      function of nasal inspired ventilation compared with total or oral inspired
      ventilation (P < 0.01), but GG activity showed no significant breathing-route
      dependence. Peak NDM integrated EMG activity decreased (P = 0.008), and peak GG
      integrated EMG activity increased (P = 0.032) coincident with the switch from
      nasal to oronasal breathing. In conclusion, 1) neural drive to NDM and GG
      increases as a function of exercise intensity, but the increase is unaltered by
      posture; 2) NDM activity is breathing-route dependent in steady-state exercise,
      but GG activity is not; and 3) drive to both muscles changes significantly at the
      switch point, but the change in GG activity is more variable and is often
      transient. This suggests that factors other than the breathing route dominate
      drive to the GG soon after the initial changes in the configuration of the
      oronasal airway are made.

PMID- 10926643
TI  - Evaluation of a new body composition phantom for quality control and cross
      calibration of DXA devices.
AB  - This study evaluated a new body composition phantom and its use for quality
      control and cross-calibration of dual-energy X-ray absorptiometry (DXA)
      instruments for measurements of body composition. We imaged the variable
      composition phantom (Lunar, Madison, WI) on eight different DXA devices.
      Deviations of up to 7% fat were observed when we compared the percent fat values
      measured by the different devices with the nominal values provided by the
      manufacturer. Absolute precision error of percent fat measurements for the
      phantom ranged from 0.6 to 0.8%. The phantom's percent fat values were also
      compared with whole body composition measurements from 130 female and male
      volunteers. The phantom detected differences in percent fat values that were
      similar to those found by comparing in vivo measurements with values from
      different DXA scanner models from the same manufacturer. When comparing different
      models of scanners from different manufacturers, such as the Hologic QDR-4500 and
      the Lunar DPX-IQ, the phantom showed a different relationship than was seen for
      patients. Therefore, corrections or comparisons based on the phantom data alone
      would be incorrect. In conclusion, the Lunar variable composition phantom is
      capable of accurately measuring the fat calibration of DXA devices and may be
      suitable for cross-sectional cross-calibration between scanners from the same
      manufacturer; however, for comparison of DXA scanners from different
      manufacturers, in vivo cross-calibration is still the only accurate method. The
      phantom may be used in longitudinal quality control to verify an instrument's
      temporal stability.

PMID- 10926644
TI  - A physiological level of clenbuterol does not prevent atrophy or loss of force in
      skeletal muscle of old rats.
AB  - Supraphysiological levels of clenbuterol (CL) reduce muscle degradation in both
      young and old animals; however, these pharmacological levels induce side effects
      that are unacceptable in the elderly. In this study, we tested the hypothesis
      that a "physiological" dose of CL (10 microg. kg(-1). day(-1)) would attenuate
      the loss of in situ isometric force and mass in muscles of senescent rats during
      hindlimb suspension (HS). Adult (3 mo) and senescent (38 mo) Fischer 344 x Brown
      Norway rats received CL or a placebo during 21 days of normal-weight-bearing or
      HS conditions (8 rats/age group). HS reduced soleus muscle weight-to-body weight
      ratio by 31%, muscle cross-sectional area by 37%, and maximal isometric tetanic
      force (P(o)) by 76% in senescent rats. CL attenuated the loss of P(o) and muscle
      weight by 17 and 8%, respectively, in the soleus of senescent rats relative to
      HS+placebo conditions, but it did not improve muscle weight normalized for body
      weight. CL did not reduce the decrease in soleus P(o) or mass after HS in adult
      rats. CL failed to reduce the loss of plantaris weight (-20%) and P(o) (-46%) in
      senescent rats after HS. Our data support the conclusion that physiological
      levels of CL do not improve fast muscle atrophy and only modestly reduce slow
      muscle atrophy, and, therefore, it is largely an ineffective countermeasure for
      preventing muscle wasting from HS in senescent rats.

PMID- 10926645
TI  - Body composition techniques and the four-compartment model in children.
AB  - The purpose of this study was to compare the accuracy, precision, and bias of fat
      mass (FM) as assessed by dual-energy X-ray absorptiometry (DXA), hydrostatic
      weighing (HW), air-displacement plethysmography (PM) using the BOD POD body
      composition system and total body water (TBW) against the four-compartment (4C)
      model in 25 children (11.4 +/- 1.4 yr). The regression between FM by the 4C model
      and by DXA deviated significantly from the line of identity (FM by 4C model =
      0.84 x FM by DXA + 0.95 kg; R(2) = 0.95), as did the regression between FM by 4C
      model and by TBW (FM by 4C model = 0. 85 x FM by TBW - 0.89 kg; R(2) = 0.98). The
      regression between FM by the 4C model and by HW did not significantly deviate
      from the line of identity (FM by 4C model = 1.09 x FM by HW + 0.94 kg; R(2) = 0.
      95) and neither did the regression between FM by 4C (using density assessed by
      PM) and by PM (FM by 4C model = 1.03 x FM by PM + 0.88; R(2) = 0.97). DXA, HW,
      and TBW all showed a bias in the estimate of FM, but there was no bias for PM. In
      conclusion, PM was the only technique that could accurately, precisely, and
      without bias estimate FM in 9- to 14-yr-old children.

PMID- 10926646
TI  - Does gender influence human cardiovascular and renal responses to water
      immersion?
AB  - We hypothesized that women and men exhibit similar cardiovascular and renal
      responses to thermoneutral water immersion (WI) to the neck. Ten women and nine
      men underwent two sessions in random order: 1) seated nonimmersed for 5.5 h
      (control) and 2) WI for 3 h, with subjects seated nonimmersed for 1.5 h pre- and
      1 h postimmersion. We measured left atrial diameter, heart rate, arterial
      pressure, urine volume and osmolality, and urinary endothelin, urodilatin,
      sodium, and potassium excretion. No significant difference existed between groups
      in cardiovascular responses. The groups also exhibited mostly similar renal
      responses to immersion after adjustment for body mass. However, female urodilatin
      excretion per kilogram during immersion was over twofold that of men, and the
      female kaliuretic response to immersion was delayed and less pronounced relative
      to that in men. Men may excrete more potassium than women during immersion
      because men possess greater lean body mass (potassium per kilogram). Results
      obtained in men during WI may be cautiously extrapolated to women, yet urodilatin
      and potassium responses exhibit gender differences.

PMID- 10926647
TI  - Exercise-dependent growth hormone release is linked to markers of heightened
      central adrenergic outflow.
AB  - To test the hypothesis that heightened sympathetic outflow precedes and predicts
      the magnitude of the growth hormone (GH) response to acute exercise (Ex), we
      studied 10 men [age 26.1 +/- 1.7 (SE) yr] six times in randomly assigned order
      (control and 5 Ex intensities). During exercise, subjects exercised for 30 min
      (0900-0930) on each occasion at a single intensity: 25 and 75% of the difference
      between lactate threshold (LT) and rest (0.25LT, 0.75LT), at LT, and at 25 and
      75% of the difference between LT and peak (1.25LT, 1.75LT). Mean values for peak
      plasma epinephrine (Epi), plasma norepinephrine (NE), and serum GH concentrations
      were determined [Epi: 328 +/- 93 (SE), 513 +/- 76, 584 +/- 109, 660 +/- 72, and
      2,614 +/- 579 pmol/l; NE: 2. 3 +/- 0.2, 3.9 +/- 0.4, 6.9 +/- 1.0, 10.7 +/- 1.6,
      and 23.9 +/- 3.9 nmol/l; GH: 3.6 +/- 1.5, 6.6 +/- 2.0, 7.0 +/- 2.0, 10.7 +/- 2.4,
      and 13.7 +/- 2.2 microg/l for 0.25, 0.75, 1.0, 1.25, and 1.75LT, respectively].
      In all instances, the time of peak plasma Epi and NE preceded peak GH release.
      Plasma concentrations of Epi and NE always peaked at 20 min after the onset of
      Ex, whereas times to peak for GH were 54 +/- 6 (SE), 44 +/- 5, 38 +/- 4, 38 +/-
      4, and 37 +/- 2 min after the onset of Ex for 0.25-1.75LT, respectively. ANOVA
      revealed that intensity of exercise did not affect the foregoing time delay
      between peak NE or Epi and peak GH (range 17-24 min), with the exception of
      0.25LT (P < 0.05). Within-subject linear regression analysis disclosed that, with
      increasing exercise intensity, change in (Delta) GH was proportionate to both
      DeltaNE (P = 0.002) and DeltaEpi (P = 0.014). Furthermore, within-subject
      multiple-regression analysis indicated that the significant GH increment
      associated with an antecedent rise in NE (P = 0.02) could not be explained by
      changes in Epi alone (P = 0.77). Our results suggest that exercise intensity and
      GH release in the human may be coupled mechanistically by central adrenergic
      activation.

PMID- 10926648
TI  - Racial differences in visceral adipose tissue but not anthropometric markers of
      health-related variables.
AB  - This study sought to determine whether visceral adipose tissue (VAT) and/or its
      anthropometric surrogates could significantly predict health-related variables
      (HRV) in overweight Caucasian (CC) (n = 36) and African-American (AA) (n = 30)
      women. With the use of magnetic resonance imaging, findings showed significantly
      higher volume and area of VAT (P < 0.0001 for both) as well as higher
      triacylglycerol (P = 0.009) in CC compared with AA women. Furthermore, VAT
      volume, race, and VAT volume x race interaction could significantly predict
      triacylglycerol (P = 0.0094), high-density lipoprotein cholesterol (P = 0.0057),
      insulin (P = 0.0002), and insulin resistance (P < 0. 0001). Additionally, the VAT
      volume x race interaction for insulin (P = 0.040) and insulin resistance (P =
      0.003) was significant. In a separate analysis, waist circumference and race
      predicted the identical variables. Our results support the use of volume or area
      of VAT in predicting HRV in CC women; however, its use in AA women appears
      limited. In contrast, waist circumference can provide a suitable VAT alternative
      for both CC and AA women; however, VAT clearly represents the more powerful
      predictor.

PMID- 10926649
TI  - Tolerance of SP-A-deficient mice to hyperoxia or exercise.
AB  - Mice carrying a null mutation of the surfactant-associated protein A (SP-A) gene
      have normal respiratory function, but their surfactant lacks tubular myelin, is
      sensitive to protein inactivation in vitro, and contains decreased pool sizes of
      the biophysically active large-aggregate surfactant. We hypothesized that SP-A
      deficient mice would be more susceptible to exercise-induced stress and O(2)
      induced lung injury. SP-A-(-/-) and SP-A-(+/+) mice tolerated 1 h of swimming or
      45 min of running on a treadmill at 15 m/min equivalently, without alterations of
      the amount of alveolar saturated phosphatidylcholine. After 3 days of hyperoxia,
      SP-A-(-/-) mice had increased alveolar protein, but pressure-volume curves were
      not different between groups. Alveolar protein concentration was similarly
      increased in SP-A-(-/-) and SP-A-(+/+) mice after 4 days of exposure to
      hyperoxia. Survival rates were similar after 4 days of hyperoxia. SP-A-(-/-) mice
      were equally tolerant to exercise and 4 days of hyperoxia, indicating that the SP
      A-dependent alterations in surfactant did not result in functional deficits.

PMID- 10926650
TI  - Supine lower body negative pressure exercise simulates metabolic and kinetic
      features of upright exercise.
AB  - Exercise within an artificial gravity environment may help prevent microgravity
      induced deconditioning. We hypothesized that supine lower body negative pressure
      (LBNP) exercise simulates physiological and biomechanical features of upright
      exercise. Walking (4.5 +/- 0.3 km/h) and running (8.0 +/- 1.0 km/h) while supine
      within a LBNP exerciser were compared with walking and running while upright.
      Eight healthy subjects exercised for 5 min at each of the four posture/gait
      conditions. LBNP of 52 +/- 4 mmHg generated one body weight of supine ground
      reaction force (GRF). Gait parameters and GRFs were measured during the third
      minute of exercise, and heart rate and oxygen consumption were measured during
      the fifth minute. Oxygen consumption during supine LBNP treadmill exercise
      [walking: 14.6 +/- 0.9; running: 32.2 +/- 1.6 (SE) ml. min(-1). kg(-1)] was
      similar to that during upright treadmill exercise (walking: 15.1 +/- 0.9;
      running: 34.0 +/- 1.9 ml. min(-1). kg(-1)). Heart rate for supine LBNP exercise
      (grand mean: 133 +/- 11 beats/min) was also similar to that for upright exercise
      (136 +/- 11 beats/min). Footward forces integrated over each stride (330.5 +/-
      34.4 vs. 319. 1 +/- 29.6 N. s) and rate of force generation (26,483 +/- 4,310 vs.
      25,634 +/- 4,434 N/s) were similar for upright and LBNP exercise, respectively.
      Our collective results indicate that supine exercise within LBNP can simulate the
      physiological stress and GRFs that are generated during upright gait.

PMID- 10926651
TI  - Changes in respiratory control in humans induced by 8 h of hyperoxia.
AB  - In humans, 8 h of isocapnic hypoxia causes a progressive rise in ventilation
      associated with increases in the acute ventilatory responses to hypoxia (AHVR)
      and hypercapnia (AHCVR). To determine whether 8 h of hyperoxia causes the
      converse of these effects, three 8-h protocols were compared in 14 subjects: 1)
      poikilocapnic hyperoxia, with end-tidal PO(2) (PET(O(2))) = 300 Torr and end
      tidal PCO(2) (PET(CO(2))) uncontrolled; 2) isocapnic hyperoxia, with PET(O(2)) =
      300 Torr and PET(CO(2)) maintained at the subject's normal air-breathing level;
      and 3) control. Ventilation was measured hourly. AHVR and AHCVR were determined
      before and 0.5 h after each exposure. During isocapnic hyperoxia, after an
      initial increase, ventilation progressively declined (P < 0.01, ANOVA). After
      exposure to hyperoxia, 1) AHVR declined (P < 0.05); 2) ventilation at fixed
      PET(CO(2)) decreased (P < 0.05); and 3) air-breathing PET(CO(2)) increased (P <
      0.05); but 4) no significant changes in AHCVR or intercept were demonstrated. In
      conclusion, 8 h of hyperoxia have some effects opposite to those found with 8 h
      of hypoxia, indicating that there may be some "acclimatization to hypoxia" at
      normal sea-level values of PO(2).

PMID- 10926652
TI  - Total body water and ECFV measured using bioelectrical impedance analysis and
      indicator dilution in horses.
AB  - The purposes of this study were 1) to determine the compartmentation of body
      water in horses by using indicator dilution techniques and 2) to simultaneously
      measure bioelectrical impedance to current flow at impulse current frequencies of
      5 and 200 kHz to formulate predictive equations that could be used to estimate
      total body water (TBW), extracellular fluid volume (ECFV), and intracellular
      fluid volume (ICFV). Eight horses and ponies weighing from 214 to 636 kg had
      catheters placed into the left and right jugular veins. Deuterium oxide, sodium
      thiocyanate, and Evans blue were infused for the measurement of TBW, ECFV, and
      plasma volume (PV), respectively. Bioelectrical impedance was measured by using a
      tetrapolar electrode configuration, with electrode pairs secured above the knee
      and hock. Measured TBW, ECFV, and PV were 0.677 +/- 0.022, 0.253 +/- 0.006, and
      0.040 +/- 0.002 l/kg body mass, respectively. Strong linear correlations were
      determined among measured variables that allowed for the prediction of TBW, ECFV,
      ICFV, and PV from measures of horse length or height and impedance. It is
      concluded that bioelectrical impedance analysis (BIA) can be used to improve the
      predictive accuracy of noninvasive estimates of ECFV and PV in euhydrated horses
      at rest.

PMID- 10926653
TI  - Relationship of interstitial fluid volume to alveolar fluid clearance in mice:
      ventilated vs. in situ studies.
AB  - Our recent report (Garat C, Carter EP, and Matthay MA. J Appl Physiol 84: 1763
      1767, 1998) described a new method to measure alveolar fluid clearance (AFC) in
      an in situ mouse preparation. However, in vivo preparations may be more suitable
      for studying alveolar fluid transport under some pathological conditions.
      Therefore, we developed a ventilated mouse model and compared AFC in the
      ventilated and the in situ mouse models. After 15 min, AFC was similar in both
      groups, but, after 30 min, AFC was 38% slower in the in situ mice (P < 0.05).
      Bilateral adrenalectomy and propranolol did not inhibit AFC after 15 min.
      Amiloride inhibited 90% of AFC in both groups. To evaluate the mechanism for the
      slower AFC in the in situ mouse preparation, we measured the extravascular lung
      water and calculated interstitial fluid volume. Extravascular lung water and
      interstitial fluid volume were greater in the in situ mice than in the ventilated
      mice at 30 min (P < 0.05). These results indicate that mouse AFC is fast, highly
      amiloride sensitive, and independent of endogenous catecholamines during the
      first 15 min. Accumulation of interstitial fluid probably plays an important role
      in slowing AFC in the in situ mouse lung model at later time intervals. These
      mouse models will be useful to quantify alveolar epithelial fluid transport under
      pathological conditions.

PMID- 10926654
TI  - Effects of desferrioxamine on serum erythropoietin and ventilatory sensitivity to
      hypoxia in humans.
AB  - In cell culture, hypoxia stabilizes a transcriptional complex called hypoxia
      inducible factor-1 (HIF-1) that increases erythropoietin (Epo) formation. One
      hallmark of HIF-1 responses is that they can be induced by iron chelation. The
      first aim of this study was to examine whether an infusion of desferrioxamine
      (DFO) increased serum Epo in humans. If so, this might provide a paradigm for
      identifying other HIF-1 responses in humans. Consequently a second aim was to
      determine whether an infusion of DFO would mimic prolonged hypoxia and increase
      the acute hypoxic ventilatory response (AHVR). Sixteen volunteers undertook two
      protocols: 1) continuous infusion of DFO over 8 h and 2) control. Epo and AHVR
      were measured at fixed times during and after the protocols. The results show
      that 1) compared with control, Epo increased in most subjects at 8 h [52.8 +/-
      57.7 vs. 6.9 +/- 2.5 (SD) mIU/ml, for DFO = 4 g/70 kg body wt, P < 0.05] and 12 h
      (63.7 +/- 76.3 vs. 7.3 +/- 2.5 mIU/ml, P < 0.001) after the start of DFO
      administration and 2) DFO had no significant effect on AHVR. We conclude that,
      whereas infusions of DFO mimic hypoxia by increasing Epo, they do not mimic
      prolonged hypoxia by augmenting AHVR.

PMID- 10926655
TI  - Effects of exercise training and ACE inhibition on insulin action in rat skeletal
      muscle.
AB  - Our laboratory has demonstrated (Steen MS, Foianini KR, Youngblood EB, Kinnick
      TR, Jacob S, and Henriksen EJ, J Appl Physiol 86: 2044-2051, 1999) that exercise
      training and treatment with the angiotensin-converting enzyme (ACE) inhibitor
      trandolapril interact to improve insulin action in insulin-resistant obese Zucker
      rats. The present study was undertaken to determine whether a similar interactive
      effect of these interventions is manifest in an animal model of normal insulin
      sensitivity. Lean Zucker (Fa/-) rats were assigned to either a sedentary,
      trandolapril-treated (1 mg. kg(-1). day(-1) for 6 wk), exercise-trained
      (treadmill running for 6 wk), or combined trandolapril-treated and exercise
      trained group. Exercise training alone or in combination with trandolapril
      significantly (P < 0.05) increased peak oxygen consumption by 26-32%. Compared
      with sedentary controls, exercise training alone or in combination with ACE
      inhibitor caused smaller areas under the curve for glucose (27-37%) and insulin
      (41-44%) responses during an oral glucose tolerance test. Exercise training alone
      or in combination with trandolapril also improved insulin-stimulated glucose
      transport in isolated epitrochlearis (33-50%) and soleus (58-66%) muscles. The
      increases due to exercise training alone or in combination with trandolapril were
      associated with enhanced muscle GLUT-4 protein levels and total hexokinase
      activities. However, there was no interactive effect of exercise training and ACE
      inhibition observed on insulin action. These results indicate that, in rats with
      normal insulin sensitivity, exercise training improves oral glucose tolerance and
      insulin-stimulated muscle glucose transport, whereas ACE inhibition has no
      effect. Moreover, the beneficial interactive effects of exercise training and ACE
      inhibition on these parameters are not apparent in lean Zucker rats and,
      therefore, are restricted to conditions of insulin resistance.

PMID- 10926656
TI  - Maximum specific force depends on myosin heavy chain content in rat diaphragm
      muscle fibers.
AB  - In the present study, myosin heavy chain (MHC) content per half sarcomere, an
      estimate of the number of cross bridges available for force generation, was
      determined in rat diaphragm muscle (Dia(m)) fibers expressing different MHC
      isoforms. We hypothesize that fiber-type differences in maximum specific force
      [force per cross-sectional area (CSA)] reflect the number of cross bridges
      present per CSA. Studies were performed on single, Triton X-100-permeabilized rat
      Dia(m) fibers. Maximum specific force was determined by activation of single
      Dia(m) fibers in the presence of a high-calcium solution (pCa, -log Ca(2+)
      concentration of 4.0). SDS-PAGE and Western blot analyses were used to determine
      MHC isoform composition and MHC content per half sarcomere. Differences in
      maximum specific force across fast MHC isoforms were eliminated when controlled
      for half-sarcomere MHC content. However, the force produced by slow fibers
      remained below that of fast fibers when normalized for the number of cross
      bridges available. On the basis of these results, the lower force produced by
      slow fibers may be due to less force per cross bridge compared with fast fibers.

PMID- 10926657
TI  - Transcriptional and translational regulation of heat shock proteins in leukocytes
      of endurance runners.
AB  - Heat shock proteins (HSP) represent cell-protective and antioxidant systems that
      may be induced by reactive oxygen species, cytokines, and hyperthermia. In the
      present study, we evaluated the influence of heavy endurance exercise and
      training on HSP27 and HSP70 in peripheral leukocytes of 12 athletes (before and
      at 0, 3, and 24 h after a half-marathon) and 12 untrained controls on protein and
      mRNA levels by flow cytometry and RT/PCR, respectively. HSP transcripts increased
      significantly immediately after acute exertion accompanied by elevated levels of
      corresponding proteins. HSP protein expression remained high until 24 h
      postexercise. Significant increases of plasma interleukin-8, myeloperoxidase, and
      creatine kinase occurred after exercise. Basal HSP expression was usually lower
      in trained compared with untrained subjects. Applying in vitro heat shock to
      resting blood samples of all subjects significantly stimulated HSP mRNA, showing
      higher increases in trained individuals. The exercise-induced alterations
      indicate that immunocompetent cells became activated. In addition to heat stress,
      other exercise-associated stress agents (oxidants, cytokines) may have also
      participated in stimulation of HSP expression in leukocytes. The expression
      pattern of HSP due to training status may be attributed to adaptive mechanisms.

PMID- 10926658
TI  - Potent bronchoprotective effect of deep inspiration and its absence in asthma.
AB  - In the absence of deep inspirations, healthy individuals develop
      bronchoconstriction with methacholine inhalation. One hypothesis is that deep
      inspiration results in bronchodilation. In this study, we tested an alternative
      hypothesis, that deep inspiration acts as a bronchoprotector. Single-dose
      methacholine bronchoprovocations were performed after 20 min of deep breath
      inhibition, in nine healthy subjects and in eight asthmatics, to establish the
      dose that reduces forced expiratory volume in 1 s by >15%. The provocation was
      repeated with two and five deep inspirations preceding methacholine. Additional
      studies were carried out to assess optimization and reproducibility of the
      protocol and to rule out the possibility that bronchoprotection may result from
      changes in airway geometry or from differential spasmogen deposition. In healthy
      subjects, five deep inspirations conferred 85% bronchoprotection. The
      bronchoprotective effect was reproducible and was not attributable to increased
      airway caliber or to differential deposition of methacholine. Deep inspirations
      did not protect the bronchi of asthmatics. We demonstrated that bronchoprotection
      is a potent physiologic function of lung inflation and established its absence,
      even in mild asthma. This observation deepens our understanding of airway
      dysfunction in asthma.

PMID- 10926660
TI  - In situ localization of cholesterol in skeletal muscle by use of a monoclonal
      antibody.
AB  - A common perception is that cholesterol, the major structural lipid found in
      mammalian membranes, is localized nearly exclusively to the plasma membrane of
      living cells and that it is found in much smaller quantities in internal
      membranes. This perception is based almost exclusively on cell fractionation
      studies, in which density gradient centrifugation is used for purification of
      discrete subcellular membrane fractions. Here we describe a monoclonal antibody,
      MAb 2C5-6, previously reported to detect purified cholesterol in synthetic
      membranes (Swartz GM Jr, Gentry MK, Amende LM, Blanchette-Mackie EJ, and Alving
      CR. Proc Natl Acad Sci USA 85: 1902-1906, 1988), that is capable of detecting
      cholesterol in situ in the membranes of skeletal muscle sections. Localization of
      cholesterol, the dihydropyridine receptor of the T tubule, and the Ca(2+)-ATPase
      of the sarcoplasmic reticulum (SERCA2) by means of double and triple
      immunostaining protocols clearly demonstrates that cholesterol is primarily
      localized to the sarcoplasmic reticulum membranes of skeletal muscle rather than
      the sarcolemmal or T tubule membranes. The availability of this reagent and its
      ability to spatially localize cholesterol in situ may provide a greater
      understanding of the relationship between membrane cholesterol content and
      transmembrane signaling in skeletal muscle.

PMID- 10926659
TI  - Pulmonary gas exchange during exercise in women: effects of exercise type and
      work increment.
AB  - Exercise-induced arterial hypoxemia (EIAH) has been reported in male athletes,
      particularly during fast-increment treadmill exercise protocols. Recent reports
      suggest a higher incidence in women. We hypothesized that 1-min incremental
      (fast) running (R) protocols would result in a lower arterial PO(2) (Pa(O(2)))
      than 5-min increment protocols (slow) or cycling exercise (C) and that women
      would experience greater EIAH than previously reported for men. Arterial blood
      gases, cardiac output, and metabolic data were obtained in 17 active women [mean
      maximal O(2) uptake (VO(2 max)) = 51 ml. kg(-1). min(-1)]. They were studied in
      random order (C or R), with a fast VO(2 max) protocol. After recovery, the women
      performed 5 min of exercise at 30, 60, and 90% of VO(2 max) (slow). One week
      later, the other exercise mode (R or C) was similarly studied. There were no
      significant differences in VO(2 max) between R and C. Pulmonary gas exchange was
      similar at rest, 30%, and 60% of VO(2 max). At 90% of VO(2 max), Pa(O(2)) was
      lower during R (mean +/- SE = 94 +/- 2 Torr) than during C (105 +/- 2 Torr, P <
      0.0001), as was ventilation (85.2 +/- 3.8 vs. 98.2 +/- 4.4 l/min BTPS, P <
      0.0001) and cardiac output (19.1 +/- 0.6 vs. 21.1 +/- 1.0 l/min, P < 0.001).
      Arterial PCO(2) (32.0 +/- 0.5 vs. 30.0 +/- 0.6 Torr, P < 0.001) and alveolar
      arterial O(2) difference (A-aDO(2); 22 +/- 2 vs. 16 +/- 2 Torr, P < 0.0001) were
      greater during R. Pa(O(2)) and A-aDO(2) were similar between slow and fast. Nadir
      Pa(O(2)) was </=80 Torr in four women (24%) but only during fast-R. In all
      subjects, Pa(O(2)) at VO(2 max) was greater than the lower 95% prediction limit
      calculated from available data in men (n = 72 C and 38 R) for both R and C. These
      data suggest intrinsic differences in gas exchange between R and C, due to
      differences in ventilation and also efficiency of gas exchange. The Pa(O(2))
      responses to R and C exercise in our 17 subjects do not differ significantly from
      those previously observed in men.

PMID- 10926661
TI  - Pulmonary blood flow remains fractal down to the level of gas exchange.
AB  - The spatial distribution of pulmonary blood flow is increasingly heterogeneous as
      progressively smaller lung regions are examined. To determine the extent of
      perfusion heterogeneity at the level of gas exchange, we studied blood flow
      distributions in rat lungs by using an imaging cryomicrotome. Approximately
      150,000 fluorescent 15-microm-diameter microspheres were injected into tail veins
      of five awake rats. The rats were heavily anesthetized; the lungs were removed,
      filled with an optimal cutting tissue compound, and frozen; and the spatial
      location of every microsphere was determined. The data were mathematically
      dissected with the use of an unbiased random sampling method. The coefficients of
      variation of microsphere distributions were determined at varying sampling
      volumes. Perfusion heterogeneity increased linearly on a log-log plot of
      coefficient of variation vs. volume, down to the smallest sampling size of 0.53
      mm(3). The average fractal dimension, a scale-independent measure of perfusion
      distribution, was 1.2. This value is similar to that of other larger species such
      as dogs, pigs, and horses. Pulmonary perfusion heterogeneity increases
      continuously and remains fractal down to the acinar level. Despite the large
      degree of perfusion heterogeneity at the acinar level, gases are efficiently
      exchanged.

PMID- 10926662
TI  - Aging reduces adaptive capacity and stress protein expression in the liver after
      heat stress.
AB  - A decline in an organism's ability to cope with stress through acute response
      protein expression may contribute to stress intolerance with aging. We
      investigated the influence of aging on stress tolerance and the capacity to
      synthesize the 70-kDa heat shock protein (HSP70) in young and old rats exposed to
      an environmental heating protocol. Livers were assessed for injury and HSP70
      expression after heat stress by use of immunohistochemical and immunoblotting
      techniques. The inducible HSP70 response in the cytoplasm and nucleus was
      markedly reduced with age at several time points over a 48-h recovery period,
      although senescent rats were able to strongly express HSP70 early in recovery.
      Older animals had extensive zone-specific liver injury, which corresponded to the
      diminished HSP70 response observed in these regions, and a significant reduction
      in thermotolerance compared with their young counterparts. These data highlight
      the regional nature of stress-induced injury and HSP70 expression in the liver
      and the impact of aging on these responses. Furthermore, the results suggest a
      functional link between the age-related decrements in the expression of inducible
      HSP70 and the pathophysiological responses to heat stress.

PMID- 10926663
TI  - Vagal feedback in the entrainment of respiration to mechanical ventilation in
      sleeping humans.
AB  - We studied the capacity of four "normal" and six lung transplant subjects to
      entrain neural respiratory activity to mechanical ventilation. Two transplant
      subjects were studied during wakefulness and demonstrated entrainment
      indistinguishable from that of normal awake subjects. We studied four normal
      subjects and four lung transplant subjects during non-rapid eye movement (NREM)
      sleep. Normal subjects entrained to mechanical ventilation over a range of
      ventilator frequencies that were within +/-3-5 breaths of the spontaneous
      respiratory rate of each subject. After lung transplantation, during which the
      vagi were cut, subjects did demonstrate entrainment during NREM sleep; however,
      entrainment only occurred at ventilator frequencies at or above each subject's
      spontaneous respiratory rate, and entrainment was less effective. We conclude
      that there is no absolute requirement for vagal feedback to induce entrainment in
      subjects, which is in striking contrast to anesthetized animals in which vagotomy
      uniformly abolishes entrainment. On the other hand, vagal feedback clearly
      enhances the fidelity of entrainment and extends the range of mechanical
      frequencies over which entrainment can occur.

PMID- 10926664
TI  - Central histamine contributed to temperature-induced polypnea in mice.
AB  - Breathing pattern is influenced by body temperature. However, the central
      mechanism for changing breathing patterns is unknown. Central histamine is
      involved in heat loss mechanisms in behavioral studies, but little is known about
      its effect on breathing patterns. We examined first the effect of body
      temperature on breathing patterns with increasing hypercapnia in conscious mice
      and then that of the depletion of central histamine by S(+)-alpha
      fluoromethylhistidine hydrochloride (alpha-FMH) (100 mg/kg ip), a specific
      inhibitor of histidine decarboxylase, at normal and raised body temperatures. A
      raised body temperature increased respiratory frequency with reductions in both
      inspiratory and expiratory time and decreased tidal volume. On the other hand,
      alpha-FMH lowered respiratory frequency with a prolongation of expiratory time at
      the raised temperature; however, this was not observed at a normal temperature.
      These results indicate that central histamine contributes to an increase in
      respiratory frequency as a result of a reduction in expiratory time when body
      temperature is raised.

PMID- 10926666
TI  - Volume-timing relationships during cough and resistive loading in the cat.
AB  - The relationship between pulmonary volume-related feedback and inspiratory (CTI)
      and expiratory (CTE) phase durations during cough was determined. Cough was
      produced in anesthetized cats by mechanical stimulation of the intrathoracic
      tracheal lumen. During eupnea, the animals were exposed to single-breath
      inspiratory and expiratory resistive loads. Cough was associated with large
      increases in inspiratory volume (VI) and expiratory volume (VE) but no change in
      phase durations compared with eupnea. There was no relationship between VI and
      CTI during coughing. A linear relationship with a negative slope existed between
      VI and eupneic inspiratory time during control and inspiratory resistive loading
      trials. There was no relationship between VE and CTE during all coughs. However,
      when the first cough in a series or a single cough was analyzed, the VE/CTE
      relationship had a positive slope. A linear relationship with a negative slope
      existed between VE and eupneic expiratory time during control and expiratory
      resistive loading trials. These results support separate ventilatory pattern
      regulation during cough that does not include modulation of phase durations by
      pulmonary volume-related feedback.

PMID- 10926665
TI  - Preservation of neural function in the perinate by high PGE(2) levels acting via
      EP(2) receptors.
AB  - Despite increasingly frequent and longer lasting hypoxic episodes during
      progressive labor, the neonate is alert and vigorous at birth. We investigated
      whether high levels of PGs during the perinatal period assist in preserving
      neural function after such "stressful" hypoxic events. Visual evoked potentials
      (VEPs) and electroretinograms (ERGs) were recorded before and 45 min after mild
      moderate asphyxic hypoxia (two 4-min asphyxic-hypoxic periods induced by
      interrupting ventilation at 8-min intervals) in newborn piglets <12 h old treated
      or not treated with inhibitors of PG synthase (ibuprofen or diclofenac) with or
      without PG analogs. At 45 min after the hypoxic episode, P2 and b-wave amplitudes
      were slightly decreased and latencies were delayed. These changes in the VEP and
      ERG returned to near normal by 120 min. Ibuprofen and diclofenac decreased brain
      and retinal PG levels and markedly intensified 45 min after hypoxia-induced
      changes in VEP and ERG, but cerebral and retinal blood flows improved. Combined
      treatment with PG synthase inhibitor in combination with 16,16-dimethyl-PGE(2) (a
      PGE(2) analog), but not with PGI(2) and PGF(2alpha) analogs, and in combination
      with the EP(2) receptor agonist butaprost (but not EP(1) or EP(3) agonists),
      prevented ibuprofen- and diclofenac-aggravated postasphyxia electrophysiological
      changes. In conclusion, high levels of PGE(2) in nervous tissue, via actions on
      EP(2) receptors, seem to contribute to preservation of neural function in the
      perinate subjected to frequent hypoxic events.

PMID- 10926667
TI  - Natural history of severe decompression sickness after rapid ascent from air
      saturation in a porcine model.
AB  - We developed a swine model to describe the untreated natural history of severe
      decompression sickness (DCS) after direct ascent from saturation conditions. In a
      recompression chamber, neutered male Yorkshire swine were pressurized to a
      predetermined depth from 50-150 feet of seawater [fsw; 2.52-5.55 atmospheres
      absolute (ATA)]. After 22 h, they returned to the surface (1 ATA) at 30 fsw/min
      (0.91 ATA/min) without decompression stops and were observed. Depth was the
      primary predictor of DCS incidence (R = 0.52, P < 0.0001) and death (R = 0.54, P
      < 0.0001). Severe DCS, defined as neurological or cardiopulmonary impairment,
      occurred in 78 of 128 animals, and 42 of 51 animals with cardiopulmonary DCS died
      within 1 h after surfacing. Within 24 h, 29 of 30 survivors with neurological DCS
      completely resolved their deficits without intervention. Pretrial Monte Carlo
      analysis decreased subject requirement without sacrificing power. This model
      provides a useful platform for investigating the pathophysiology of severe DCS
      and testing therapeutic interventions. The results raise important questions
      about present models of human responses to similar decompressive insults.

PMID- 10926668
TI  - Exercise in the heat is limited by a critical internal temperature.
AB  - We examined whether fatigue during exertional heat stress occurred at a critical
      internal temperature independent of the initial temperature at the start of
      exercise. Microwaves (2.1 GHz; 100 mW/cm(2)) were used to rapidly (3-8 min) heat
      rats before treadmill exercise to exhaustion. In a repeated-measures design, food
      restricted male Sprague-Dawley rats (n = 11) were preheated to three levels (low,
      medium, and high). In addition, two sham exposures, Sham 1 and Sham 2, were
      administered at the beginning and end of the study, respectively. At the
      initiation of exercise, hypothalamic (T(hyp)) and rectal (T(rec)) temperatures
      ranged from 39.0 degrees C to 42.8 degrees C (T(hyp)) and 42.1 degrees C
      (T(rec)). The treadmill speed was 17 m/min (8 degrees grade), and the ambient
      temperature during exercise was 35 degrees C. Each treatment was separated by 3
      wk. Run time to exhaustion was significantly reduced after preheating. There was
      a significant negative correlation between run time and initial T(hyp) and T(rec)
      (r = 0.73 and 0.74, respectively). The temperatures at exhaustion were not
      significantly different across treatments, with a range of 41.9-42.2 degrees C
      (T(hyp)) and 42.2-42.5 degrees C (T(rec)). There were no significant differences
      in run time in the sham runs administered at the start and end of the
      investigation. No rats died as a result of exposure to any of the treatments, and
      body weight the day after each treatment was unaffected. These results support
      the concept that a critical temperature exists that limits exercise in the heat.

PMID- 10926669
TI  - Continuous intracellular recording from mammalian neurons exposed to hyperbaric
      helium, oxygen, or air.
AB  - We developed a hyperbaric chamber for intracellular recording in rat brain stem
      slices during continuous compression and decompression of the tissue bath with
      the inert gas helium. Air, rather than helium, was also used as the compression
      medium in some cases to increase tissue nitrogen levels. An important feature is
      the chamber door, which opens or closes rapidly at 1 atmosphere absolute (ATA)
      for increased accessibility of the microelectrode. The door also closes and seals
      smoothly without disrupting the intracellular recording. Hyperbaric oxygen was
      administered during helium compression using a separate pressure cylinder filled
      with perfusate equilibrated with 2. 3-3.3 ATA oxygen. Measurements of tissue/bath
      PO(2) and pH confirmed that the effects of compression using helium or air could
      be differentiated from those due to increased PO(2). One hundred and thirteen
      neurons were studied during 375 compression cycles ranging from 1 to 20 ATA (mode
      3.0 ATA). We conclude that it is technically feasible to record intracellularly
      from the same mammalian neuron while changing ambient pressure over a
      physiologically important range. These techniques will be useful for studying how
      various hyperbaric environments affect neurophysiological mechanisms.

PMID- 10926670
TI  - Physiology of a microgravity environment invited review: microgravity and
      skeletal muscle.
AB  - Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force
      and power; and, in the first few weeks, a preferential atrophy of extensors over
      flexors. The atrophy primarily results from a reduced protein synthesis that is
      likely triggered by the removal of the antigravity load. Contractile proteins are
      lost out of proportion to other cellular proteins, and the actin thin filament is
      lost disproportionately to the myosin thick filament. The decline in contractile
      protein explains the decrease in force per cross-sectional area, whereas the thin
      filament loss may explain the observed postflight increase in the maximal
      velocity of shortening in the type I and IIa fiber types. Importantly, the
      microgravity-induced decline in peak power is partially offset by the increased
      fiber velocity. Muscle velocity is further increased by the microgravity-induced
      expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and
      by the increased expression of fast type II fiber types. SF increases the
      susceptibility of skeletal muscle to damage, with the actual damage elicited
      during postflight reloading. Evidence in rats indicates that SF increases
      fatigability and reduces the capacity for fat oxidation in skeletal muscles.
      Future studies will be required to establish the cellular and molecular
      mechanisms of the SF-induced muscle atrophy and functional loss and to develop
      effective exercise countermeasures.

PMID- 10926672
TI  - commentary

PMID- 10926671
TI  - Invited review: what do we know about the effects of spaceflight on bone?
AB  - This review of the peer-reviewed literature focuses on the effects of spaceflight
      on bone. Studies performed in humans and laboratory animals have revealed
      abnormalities in bone and mineral metabolism that suggest that long-duration
      spaceflight will have detrimental effects on the skeleton. However, because of
      large gaps in our knowledge, it is not presently possible to estimate the
      magnitude of the health risk, individual variations in risk, effective
      countermeasures, or mechanism(s) of action. Specific recommendations are made for
      future research to ascertain risk and develop appropriate countermeasures.

PMID- 10926673
TI  - Physiology of a microgravity environment selected contribution: effects of
      spaceflight during pregnancy on labor and birth at 1 G.
AB  - The events of parturition (labor, delivery, maternal care, placentophagia, and
      onset of nursing) were analyzed in female Norway rats (Rattus norvegicus) flown
      on either 11- or 9-day-long spaceflights beginning at the approximate midpoint of
      their pregnancies. Each space shuttle flight landed on the 20th day of the rats'
      pregnancies, just 48-72 h before parturition. After spaceflight, dams were
      continuously monitored and recorded by time-lapse videography throughout the
      completion of parturition and onset of nursing (days 22 and 23). Analyses of
      parturition revealed that, compared with ground controls, flight dams displayed
      twice the number of lordosis contractions, the predominant labor contraction type
      in rats. The number of vertical contractions (those that immediately precede
      expulsion of a pup from the womb), the duration of labor, fetal wastage, number
      of neonates born, neonatal birth weights, placentophagia, and maternal care
      during parturition, including the onset of nursing, were comparable in flight and
      ground control dams. Our findings indicate that, with the exception of labor
      contractions, mammalian pregnancy and parturition remain qualitatively and
      quantitatively intact after spaceflight during pregnancy.

PMID- 10926674
TI  - Selected contribution: PKC activation inhibits Ca(2+) signaling in tracheal
      epithelial cells kept in simulated microgravity.
AB  - Microgravity has been shown to alter protein kinase C (PKC) activity; therefore,
      we investigated whether microgravity influences mechanically stimulated Ca(2+)
      signaling and ATP-induced Ca(2+) oscillations, both of which are modulated by
      PKC. Rabbit tracheal epithelial outgrowth cultures or suspended epithelial sheets
      were rotated in bioreactors to simulate microgravity. Mechanical stimulation of a
      single cell increased the cytosolic Ca(2+) concentration in 35-55 cells of both
      outgrowth cultures and epithelial sheets kept at unit gravity (G) or in simulated
      microgravity (smicroG). In outgrowth cultures, 12-O-tetradecanoylphorbol-13
      acetate (TPA; 80 nM), a PKC activator, restricted Ca(2+) "waves" to about 10
      cells in unit G and to significantly fewer cells in smicroG. TPA only slightly
      reduced the spread of Ca(2+) waves in epithelial sheets kept in smicroG but did
      not inhibit Ca(2+) waves of sheets kept in unit G. In both cell preparations from
      both conditions, TPA inhibited ATP-induced Ca(2+) oscillations; however, the
      effect was more pronounced in cells kept in smicroG. These results suggest that
      PKC activation is more robust in cells subjected to smicroG.

PMID- 10926675
TI  - Thermodynamics of fatty acid transfer.
AB  - There is continuing controversy about the mechanism for transfer of fatty acids
      (FA) between plasma and the interior of cells and vice versa. One view is that
      this is a spontaneous process. The generally accepted view is that each step of
      the process is facilitated by a specialized protein. Whether uptake is
      spontaneous or facilitated, the components of the uptake system, e.g., albumin,
      water, FA, plasma membrane, and putative transport proteins of the plasma
      membrane, must behave according to the rules of the physical chemistry of the
      system. We review these features to illustrate the constraints they impose on the
      design of experiments to adduce the mechanism of uptake. Analysis of the
      literature in the context of the physical chemistry of the uptake system
      indicates that arguments for a facilitated mechanism of uptake for FA are not
      supported by any data extant. By contrast, comparison of the rates for individual
      steps of the pathway traversed by FA moving from albumin to the inside of a cell
      (or vesicles of a model system) with rates of uptake of FA of tissues in the
      steady state shows that the rates of the former are sufficient to account for the
      rate of the latter.

PMID- 10926676
TI  - Glycoside binding and translocation in Na(+)-dependent glucose cotransporters:
      comparison of SGLT1 and SGLT3.
AB  - Using cotransporters as drug delivery vehicles is a topic of continuing interest.
      We examined glucose derivatives containing conjugated aromatic rings using two
      isoforms of the Na(+)/glucose cotransporter: human SGLT1 (hSGLT1) and pig SGLT3
      (pSGLT3, SAAT1). Our studies indicate that there is similarity between SGLT1 and
      SGLT3 in the overall architecture of the vestibule leading to the sugar-binding
      site but differences in translocation pathway interactions. Indican was
      transported by hSGLT1 with higher affinity (K(0.5) 0.06 mm) and 2-naphthylglucose
      with lower affinity (K(0.5) 0. 5 mm) than alpha-methyl-d-glucopyranoside (alpha
      MDG, 0.2 mm). Both were poorly transported (maximal velocities, I(max), 14% and
      8% of alpha MDG). Other compounds were inhibitors (K(i)s 1-13 mm). In pSGLT3,
      indican and 2-naphthylglucose were transported with higher affinity than alpha
      MDG (K(0.5)s 0.9, 0.2 and 2.5 mm and relative I(max)s of 80, 25 and 100%).
      Phenylglucose and arbutin were transported with higher I(max)s (130 and 120%) and
      comparable K(0. 5)s (8 and 1 mm). Increased affinity of indican relative to
      alphaMDG suggests that nitrogen in the pyrrole ring is favorable in both
      transporters. Higher affinity of 2-naphthylglucose for pSGLT3 than hSGLT1
      suggests more extensive hydrophobic/aromatic interaction in pSGLT3 than in
      hSGLT1. Our results indicate that bulky hydrophobic glucosides can be transported
      by hSGLT1 and pSGLT3, and discrimination between them is based on steric factors
      and requirements for H-bonding. This provides information for design of
      glycosides with potential therapeutic value.

PMID- 10926677
TI  - Analysis of the structure and electrophysiological actions of halitoxins: 1,3
      alkyl-pyridinium salts from Callyspongia ridleyi.
AB  - We have chemically characterized a preparation of halitoxins, (1,3 alkyl
      pyridinium salts) isolated from the marine sponge Callyspongia ridleyi. At
      concentrations of 50 and 5 microg/ml the halitoxin preparation caused
      irreversible membrane potential depolarization, decreased input resistance and
      inhibited evoked action potentials when applied to cultured dorsal root ganglion
      neurones. Under whole cell voltage clamp the halitoxins produced an increase in
      cation conductance that was attenuated by replacing sodium with N-methyl-d
      glucamine. Fura-2 fluorescence ratiometric calcium imaging was used to directly
      measure calcium flux into neurones after exposure to halitoxins. Calcium influx,
      evoked by the halitoxins, persisted when the neurones were bathed in medium
      containing the voltage-activated calcium channel antagonists cadmium and nickel.
      Experiments on undifferentiated F-11 cells showed little or no calcium influx in
      response to depolarizing concentrations of potassium and indicated that
      halitoxins evoked massive calcium influx in the absence of voltage-activated
      calcium channels. The halitoxins also produced transient increases in
      intracellular calcium when F-11 cells were bathed in calcium-free medium
      suggesting that the toxins could release calcium from intracellular stores. The
      pore-forming action of the halitoxins was identified when the toxins were applied
      to artificial lipid bilayers composed of phosphatidylcholine and cholesterol.
      Halitoxins evoked channel-like activity in the lipid bilayers, with estimated
      unitary conductances of between 145pS and 2280pS, possibly indicating that
      distinct channels could be produced by the different components in the
      preparation of halitoxins.

PMID- 10926679
TI  - Cleavage of disulfide bonds leads to inactivation and degradation of the type
      IIa, but not type IIb sodium phosphate cotransporter expressed in Xenopus laevis
      oocytes.
AB  - Tris(2-carboxyethyl)phosphine (TCEP) reduces (cleaves) disulfide bonds of the
      renal proximal tubule type IIa Na/Pi- cotransporter (rat NaPi IIa) and thereby
      inhibits its function. We tested the effect of TCEP on the murine type IIa
      Na/P(i)-cotransporter and the corresponding IIb intestinal isoform both expressed
      in Xenopus laevis oocytes. After incubation with TCEP the function of NaPi IIa
      was inhibited and protein amount was decreased. Injection of the lysosomal
      inhibitor leupeptin prevented degradation of the protein. Exposure of oocytes to
      TCEP at 0 degrees C led to a reduction in transport function without concomitant
      loss in Na/Pi IIa protein. In contrast to NaPi type IIa, the type IIb isoform was
      neither inhibited, nor degraded after incubation with TCEP. These results suggest
      that cleavage of disulfide bonds led to changes within the confirmation of the
      type IIa transporter that result in (i) inhibition of the transport activity and
      (ii) internalization and subsequent lysosomal degradation of transporter protein.
      Sequence comparisons suggest the involvement/presence of different disulfide
      bonds in type IIa and type IIb Na/P(i)-cotransporters.

PMID- 10926678
TI  - Cysteine residues and the structure of the rat renal proximal tubular type II
      sodium phosphate cotransporter (rat NaPi IIa).
AB  - The rat renal Na/P(i) cotransporter type IIa (rat NaP(i) IIa) is a 637 amino acid
      protein containing 12 cysteine residues. We examined the effect of different
      cysteine modifying methanethiosulfonate (MTS)-reagents and the disulfide bond
      reducing agent tris(2-carboxyethyl)phosphine (TCEP) on the transport activity of
      wild-type and 12 single cysteine substitution mutants of rat NaPi IIa expressed
      in Xenopus laevis oocytes. The transport activity of the wild-type protein was
      resistant to three membrane impermeant MTS-reagents (MTSEA, MTSET and MTSES). In
      contrast, membrane permeant methyl methanethiosulfonate (MMTS) and TCEP inhibited
      the transport activity of both the wild-type, as well as all the single mutant
      proteins. This indicated the existence of more than one functionally important
      cysteine residue, not accessible extracellularly, and at least 2 disulfide
      bridges. To identify the disulfide bridges, three double mutants lacking 2 of the
      3 cysteine residues predicted to be extracellular in different combinations were
      examined. This led to the identification of one disulfide bridge between C306 and
      C334; reconsideration of the topological model predictions suggested a second
      disulfide bridge between C225 and C520. Evaluation of a fourth double mutant
      indicated that at least one of two disulfide bridges (C306 and C334; C225 and
      C520) has to be formed to allow the surface expression of a functional
      cotransporter. A revised secondary structure is proposed which includes two
      partially repeated motifs that are connected by disulfide bridges formed between
      cysteine pairs C306-C334 and C225-C520.

PMID- 10926680
TI  - Water permeability in rat oocytes at different maturity stages: aquaporin-9
      expression.
AB  - Important functional and structural modifications occur in mammalian oocytes
      during their arrival to maturity. In this process, oocytes switch from a high
      activity level, implying an important metabolic rate and a coordinated movement
      of water and solutes, to a lower functional state. The aim of this work was to
      study the mechanisms involved in water movements during oocyte arrival to
      maturity. Volume changes, induced by an osmotic gradient, were followed by video
      microscopy in rat oocytes. The water osmotic permeability (P(osm)) of immature
      oocytes (proestrus) was sensitive to HgCl(2) and phloretin. In contrast, mature
      oocytes (estrus) had a reduced P(osm) that was not sensitive to these compounds.
      When proestrus oocytes were incubated in vitro at 37 degrees C they spontaneously
      arrived at maturity and its P(osm) decreased between four and six hours of
      incubation. RT-PCR experiments were performed using specific primers for all rat
      aquaporins that had been cloned. We found that aquaporin-9 transcript (AQP9) is
      present in proestrus oocytes but not in estrus oocytes. AQP9 has been recently
      described as a "broad selective channel" responsible for solute and water
      transfers in highly active cells. Our experiments showed that proestrus oocytes,
      but not estrus, are permeable to mannitol. It is concluded that during the
      process of maturation, P(osm) decreases and AQP9 transcripts disappear. We report
      here the first study correlating water permeability and aquaporin mRNA expression
      in mammalian oocytes.

PMID- 10926681
TI  - The conserved motif in hydrophilic loop 2/3 and loop 8/9 of the lactose permease
      of Escherichia coli. Analysis of suppressor mutations.
AB  - The major facilitator superfamily (MFS) of transport proteins, which includes the
      lactose permease of Escherichia coli, contains a conserved motif G-X-X-X-D/E-R/K
      X-G-R/K-R/K in the loops that connect transmembrane segments 2 and 3, and
      transmembrane segments 8 and 9. In three previous studies (Jessen-Marshall, A.E.,
      & Brooker, R.J. 1996. J. Biol. Chem. 271:1400-1404; Jessen-Marshall, A.E.,
      Parker, N., & Brooker, R.J. 1997. J. Bacteriol. 179:2616-2622; and Pazdernik, N.,
      Cain, S.M., & Brooker, R.J. 1997. J. Biol. Chem. 272:26110-26116), suppressor
      mutations at twenty different sites were identified which restore function to
      mutant permeases that have deleterious mutations in the conserved loop 2/3 or
      loop 8/9 motif. In the current study, several of these second-site suppressor
      mutations have been separated from the original mutation in the conserved motif.
      The loop 2/3 suppressors were then coupled to a loop 8/9 mutation (P280L) and the
      loop 8/9 suppressors were coupled to a loop 2/3 mutation (i.e., G64S) to
      determine if the suppressors could restore function only to a loop 2/3 mutation,
      a loop 8/9 mutation, or both. The single parent mutations changing the first
      position in loop 2/3 (i.e., G64S) and loop 8/9 (i.e., P280L) had less than 4%
      lactose transport activity. Interestingly, most of the suppressors were very
      inhibitory when separated from the parent mutation. Two suppressors, A50T and
      G370V, restored substantial transport activity when individually coupled to the
      mutation in loop 2/3 and also when coupled to the corresponding mutation in loop
      8/9. In other words, these suppressors could alleviate a defect imposed by
      mutations in either half of the permease. From a kinetic analysis, these
      suppressors were shown to exert their effects by increasing the V(max) values for
      lactose transport compared with the single G64S and P280L strains. These results
      are discussed within the context of our model in which the two halves of the
      lactose permease interact at a rotationally symmetrical interface, and that
      lactose transport is mediated by conformational changes at the interface.

PMID- 10926682
TI  - Increased activity of calcium leak channels caused by proteolysis near
      sarcolemmal ruptures.
AB  - Dystrophin, a 427 kD membrane-associated structural protein in muscle cells, is
      thought to confer strength to the myofiber sarcolemma and protect the membrane
      from rupture during the stresses of contraction. Dystrophin is absent in muscle
      cells from Duchenne muscular dystrophy (DMD) patients and mdx mice, a DMD model.
      Dystrophic muscle membranes undergo more frequent transient, nonlethal tears than
      normal cell membranes, especially during exercise. In addition, the mean open
      probability of a background ("leak") calcium channel is higher in dystrophic
      muscle cells, which leads to higher intracellular free calcium levels. Because
      elevated calcium levels may contribute to the eventual necrosis of muscle cells
      in DMD, we examined the possibility that the history of sarcolemmal rupture at a
      specific location on the membrane affects the open probability of nearby calcium
      leak channels. Membrane ruptures left by the excision of cell-attached patch
      clamp electrodes were used to mimic natural tears. Patches made within 5 microns
      of excision sites contained channels with a fourfold greater mean open
      probability than channels in patches 50 microm away from ruptures. The increased
      leak channel activity near ruptures was seen continuously through the duration of
      the recordings and was not seen if the rupture was made in the presence of the
      protease inhibitor leupeptin. Calcium background channels proteolytically
      activated near ruptures, perhaps in a calcium-dependent manner, may thus be the
      lasting consequence of the weaker dystrophic sarcolemma, leading to chronically
      raised intracellular free calcium, increased calcium-dependent proteolysis and,
      eventually, necrosis.

PMID- 10926683
TI  - Lysophosphatidylcholine induces taurine release from HeLa cells.
AB  - The putative role of lysophospholipids in activation and regulation of the volume
      sensitive taurine efflux was investigated in HeLa cells using tracer technique.
      Lysophosphatidylcholine (LPC, 10 microm) with oleic acid increased taurine efflux
      during hypotonic and isotonic conditions. Substituting palmitic or stearic acid
      for oleic acid enhanced taurine release during isotonic conditions, whereas
      ethanolamine, serine or inositol containing lysophospholipids were ineffective.
      High concentrations of LPC (25 microm) induced Ca(2+) influx, loss of adenosine
      nucleotides, taurine and the Ca(2+)-sensitive probe Fura-2, and thus reflected a
      general breakdown of the membrane permeability barrier. Low concentrations of LPC
      (5-10 microm) solely induced taurine efflux. The LPC-induced taurine release was
      unaffected by anion channel blockers (DIDS, MK196) and the 5-lipoxygenase
      inhibitor ETH 615-139, which all blocked the volume sensitive taurine efflux.
      Furthermore, LPC-induced taurine release was reduced by antioxidants (NDGA,
      vitamin E) and the protein tyrosine kinase inhibitor genistein. The swelling
      induced taurine efflux was in the absence of LPC unaffected by vitamin E, blocked
      by genistein, and increased by H(2)O(2) and the protein tyrosine phosphatase
      inhibitor vanadate. It is suggested that low concentrations of LPC permeabilizes
      the plasma membrane in a Ca(2+)-independent process that involves generation of
      reactive oxygen species and tyrosine phosphorylation, and that LPC is not a
      second messenger in activation of the volume sensitive taurine efflux in HeLa
      cells.

PMID- 10926684
TI  - The morphology of quasicrystals, incommensurate composite crystals and modulated
      crystals derived from the broken-bond model.
AB  - The broken-bond model for the surface free energy of crystals is considered. The
      consequences are derived for the morphology of periodic crystals, quasicrystals,
      incommensurately modulated crystals and intergrowth compounds. It is found that
      low-index facets on periodic crystals and quasicrystals are the result of finding
      an optimized position along the vector normal to the surface of the surface
      plane. The same principle explains the normal facets on modulated crystals and
      intergrowth crystals. The so-called satellite facets are the result of surface
      pinning of the phase of the modulated wave. On intergrowth compounds, facets may
      be found that are stabilized by a combination of both mechanisms. It is shown
      that the most stable facets on intergrowth crystals are the normal facets that
      are common to the subsystems, independent of the details of the structure.

PMID- 10926685
TI  - Theory of moire fringes on X-ray diffraction topographs of bicrystals.
AB  - The theory of moire fringes on X-ray diffraction topographs of bicrystals is
      derived from the dynamical theory of X-ray diffraction for the reflection (Bragg)
      and the transmission (Laue) case. The influence on the moire fringes of the
      diffraction geometry, of the geometry of the sample, of its optical properties
      and of the topographic method is investigated. The perfect-crystal theory is also
      expanded to weakly deformed bicrystals.

PMID- 10926686
TI  - X-ray diffraction moire topography as a means to reconstruct relative
      displacement fields in weakly deformed bicrystals.
AB  - X-ray diffraction topographs of wafers produced by separation by implanted oxygen
      (SIMOX) show moire fringes in both reflection and transmission geometry. These
      fringes reveal deformations of the order of 10(-6) to 10(-8) between the layer
      and the substrate of the SIMOX material. A new method for a quantitative analysis
      of moire fringes is developed and allows reconstruction with a high sensitivity
      of the three components of the relative displacement field between layer and
      substrate directly from a set of topographs. This method is used for the
      interpretation of moire topographs of entire 4 in SIMOX wafers and of regions
      around crystal defects. Finally, the capabilities of an analysis of moire fringes
      are compared with those of the usual diffraction topo-graphy.

PMID- 10926687
TI  - Small-angle scattering by dislocations.
AB  - It is shown that the small-angle scattering of X-rays or neutrons by dislocations
      within a deformed metal, which are partially ordered into wall-like structures,
      is characterized by several factors. Principally these are associated with: (i) a
      single dislocation or dipole; (ii) the dislocation configuration in the plane of
      the wall; and (iii) the distribution of dislocations across the wall thickness.
      With the assumption of isotropic elasticity, small-angle scattering will be
      sensitive only to the edge components of the dislocations. The scattered
      intensity is dominated by scattering from dislocations that lie perpendicular to
      the scattering vector, q, and reaches a maximum when q is normal to the slip
      plane of these dislocations. Above a particular |q|, the scattered intensity is
      sensitive only to the total edge dislocation content of the scattering
      dislocations (i.e. scattering is incoherent), while, below this value, the
      scattering is dominated by how the dislocations are distributed in walls. For
      walls normal to their slip planes, the configuration factor will reflect the
      dislocation distribution in the plane of the wall, while, for walls parallel to
      their slip planes, the distribution in the thickness direction will be visible.
      Therefore, even though a deformed material is composed of complicated dislocation
      structures, only those segments conforming to these rather strict prescriptions
      will be singled out for scattering, and, by adjusting the beam/slip system
      geometry, many parameters of the microstructure can be determined experimentally.

PMID- 10926688
TI  - Three-wave grazing-incidence X-ray diffraction from thin crystal surface layers:
      determination of triplet phase invariants.
AB  - Numerical calculation of the angular and spectral distributions of the
      intensities of the specularly diffracted waves in the case of three-wave grazing
      incidence X-ray diffraction is carried out using the dynamical theory. The
      angular and spectral distributions are shown to be uniquely and continuously
      dependent upon the value of the triplet phase invariant. A method of determining
      the value of the triplet phase invariant for thin crystal surface layers is
      developed, based on the comparison of experimentally measured three-wave peak
      profiles with the profiles calculated for different values of the triplet phase
      invariant. An analysis scheme of the phase sensitivity of the reflection
      coefficients is proposed taking into account the interference of the directly
      excited and the 'Umweg'-excited specularly diffracted waves.

PMID- 10926689
TI  - About new applications of parametric X-radiation for crystallography.
AB  - A theoretical analysis of the parametric X-radiation (PXR) produced by the
      nonrelativistic electrons in an X-ray tube with a monocrystalline anode is
      presented. It is shown that PXR can be considered as a source of quasi
      monochromatic X-radiation for laboratory dif-fraction experiments. The intensity
      of the PXR is comparable with the intensity of the characteristic radiation, but
      the frequency of the former can be varied in a wide range. Possible applications
      of the phenomenon for crystallography are discussed.

PMID- 10926690
TI  - Quantitative zone-axis convergent-beam electron diffraction (CBED) studies of
      metals. I. Structure-factor measurements.
AB  - The zone-axis CBED pattern-matching technique ZAPMATCH [Bird & Saunders (1992).
      Ultramicroscopy, 45, 241-251] has been applied to low-order structure-factor
      measurements in nickel and copper. Considerable disagreement exists between
      previously published results obtained with a variety of solid-state theories and
      experimental techniques. The nickel ZAPMATCH results confirm previous electron
      diffraction critical-voltage measurements and are in excellent agreement with
      FLAPW (full-potential linearized augmented plane-wave) theory calculations. This
      is further proof of the accuracy achievable with ZAPMATCH analysis. For copper,
      however, while the results support the findings of previous experimental
      measurements, they are consistently higher than those given by a range of solid
      state theories, perhaps demonstrating some limitation in the existing theory. Two
      extensions to the ZAPMATCH technique are also considered. First, rules are
      developed to determine the number of structure factors that can be refined
      accurately from a given CBED pattern. Second, the imaginary potential generally
      introduced to account for the effects of thermal diffuse scattering (TDS) is also
      refined. It is shown that, while the widely used Einstein model is a useful
      approximation, the refined values are consistently higher than the model
      predicts. In addition, the importance of a second-order (real) TDS correction
      arising from the Einstein model is investigated. Although its effects are limited
      in this instance, it may prove to be more significant at lower beam energies or
      for materials of higher atomic number.

PMID- 10926691
TI  - Quantitative zone-axis convergent-beam electron diffraction (CBED) studies of
      metals. II. Debye-Waller-factor measurements.
AB  - Quantitative CBED techniques, such as the ZAPMATCH zone-axis pattern-matching
      method [Bird & Saunders (1992). Ultramicroscopy, 45, 241-251], have been applied
      with great success to the accurate refinement of low-order structure factors. The
      major limitation on the accuracy of the structure-factor measurements is
      uncertainty in the Debye-Waller factors describing the temperature-dependent
      atomic vibrations. While X-ray and neutron diffraction tech-niques are both
      capable of accurate measurements of Debye-Waller factors, the frequent use of
      liquid-nitrogen-cooled samples in CBED experiments means that previous
      measurements are rarely available at the temperatures required. This has prompted
      attempts to determine Debye-Waller factors from electron diffraction data
      obtained under experimental conditions that match those used for the quantitative
      CBED work. In this paper, the possibility of extracting accurate Debye-Waller
      factors from the low-order reflections of a zone-axis CBED pattern is
      investigated. In this way, the Debye-Waller factors and structure factors could
      be obtained from the same data set. With this new approach, it is shown that
      errors lower than +/-0.02 A(2) can be obtained for the measurement of Debye
      Waller factors from room- and liquid-nitrogen-temperature nickel and copper <110>
      zone-axis data. The results obtained are compared with previous measurements and
      theoretical predictions.

PMID- 10926692
TI  - X-ray phase determination by the principle of minimum charge.
AB  - When the electron density in a crystal or a quasicrystal is reconstructed from
      its Fourier modes, the global minimum value of the density is sensitively
      dependent on the relative phases of the modes. The set of phases that maximizes
      the value of the global minimum corresponds, by positivity of the density, to the
      density having the minimum total charge that is consistent with the measured
      Fourier amplitudes. Phases that minimize the total electronic charge (i.e. the
      average electron density) have the additional property that the lowest minima of
      the electron density become exactly degenerate and proliferate within the unit
      cell. The large number of degenerate minima have the effect that density maxima
      are forced to occupy ever smaller regions of the unit cell. Thus, by minimization
      of the electronic charge, the atomicity of the electron density is enhanced as
      well. Charge minimization applied to simulated crystalline and quasicrystalline
      diffraction data successfully reproduces the correct phases starting from random
      initial phases.

PMID- 10926693
TI  - The use of multiple-scattering data to enhance small-angle neutron scattering
      experiments.
AB  - Multiple scattering of neutrons by the inhomogeneities responsible for small
      angle neutron scattering (SANS) during the passage of the beam through the
      specimen can be used to provide valuable information about the shape of the
      objects and the absolute value of the contrast between the scattering particles
      and the matrix. The neutrons emerging from the specimen are classified into those
      that have been scattered n times. The index n ranges from zero to infinity. The
      remnant of the incident beam is the group of neutrons for which n equals zero.
      Each group contributes separately to the scattering profile. The small-angle
      scattering cross section is independent of the neutron wavelength for n = 1 only.
      Thus collection of data as a function of specimen thickness and of neutron
      wavelength will provide a number of different profiles describing the same
      physical situation. Simultaneous analysis of these profiles provides absolute
      values of the cross section for scattering into the small-angle region and of the
      cross section for removal of neutrons from the small-angle region. So that the
      method can be used generally, a profile function that is a very good
      approximation to those in the literature is introduced. The implications for time
      of-flight SANS are discussed.

PMID- 10926694
TI  - Quasiperiodic patterns generated by mixing lattices derived from a dodecahedral
      star and an icosahedral star.
AB  - A 3D quasiperiodic pattern by projection from an nD lattice can be defined by an
      orthonormal n x n lattice matrix which produces basis vectors in pattern space
      with a prescribed arrangement and basis vectors in perpendicular or test space
      satisfying the quasicrystallographic condition. A 16 x 16 lattice matrix is
      derived which produces basis vectors in pattern space as a combination or mixing
      of dually positioned dodecahedral star and icosahedral star. It is shown that the
      mixed star constitutes a eutactic star. Since the module generated by the mixed
      eutactic star is totally irrational, patterns generated by projection using the
      lattice matrix are quasicrystallographic and the equilateral pattern is generated
      for 1:1 mixing.

PMID- 10926695
TI  - The joint probability distribution function of structure factors with rational
      indices. IV. The P1 case.
AB  - The method of the joint probability distribution functions of structure factors
      has been extended to reflections with rational indices. The most general case,
      space group P1, has been considered. The positional parameters are the primitive
      random variables of our probabilistic approach, while the reflection indices are
      kept fixed. Quite general joint probability distributions have been considered
      from which conditional distributions have been derived: these proved applicable
      to the accurate estimation of the real and imaginary parts of a structure factor,
      given prior information on other structure factors. The method is also discussed
      in relation to the Hilbert-transform techniques.

PMID- 10926696
TI  - The joint probability distribution function of structure factors with rational
      indices. V. The estimates.
AB  - The probabilistic formulae [Giacovazzo, Siliqi & Fernandez-Castano (1999). Acta
      Cryst. A55, 512-524] relating standard and half-integral index reflections are
      modified for practical applications. The experimental tests prove the reliability
      of the probabilistic relationships. The approach is further developed to explore
      whether the moduli of the half-integral index reflections can be evaluated in the
      absence of phase information; i.e. by exploiting the moduli of the standard
      reflections only. The final formulae indicate that estimates can be obtained,
      even though the reliability factor is a constant.

PMID- 10926697
TI  - Moire patterns in electron microscopy with atomic focuser crystals.
AB  - The periodic array of very fine cross-overs formed at the exit face of a thin
      'atomic focuser' crystal, illuminated by a parallel electron beam, may be used to
      form moire patterns with a specimen crystal such that the structure of the
      specimen crystal may be derived with a resolution of better than 0.5 A. Computer
      simulations of the moire pattern formation have been made for the simple
      idealized case of two parallel gold-like lattices having a 10% difference in
      lattice constant. Moire images are shown for the case of a small objective
      aperture in the viewing electron microscope such that the individual crystal
      lattices are not resolved and for a larger objective aperture for which the
      individual crystal lattices are resolved and the intensity is measured at the
      positions of the atoms of the atomic focuser crystal. The latter case confirms
      the viability of the scheme for ultra-high-resolution imaging of general
      specimens by use of a thin-crystal periodic atomic focuser, as previously
      proposed.

PMID- 10926698
TI  - On the geometry of a modern imaging diffractometer.
AB  - The geometry of a modern imaging diffractometer is discussed in detail. A method
      to find all relevant instrument parameters from the control single-crystal
      measurement data is proposed and the limitations of such a procedure are
      indicated. Optimization of the instrument parameters by the least-squares method
      is presented.

PMID- 10926699
TI  - Positive-definite conditions of elastic constants of two-dimensional
      quasicrystals with noncrystallographic symmetries.
AB  - In the present work, the positive-definite conditions of the elastic constants of
      two-dimensional (2D) quasicrystals with non-crystallographic symmetries have been
      derived. These results are necessary for studying elastic and mechanical
      properties of two-dimensional quasicrystals both in theory and in experiment.
      Project supported by the National Natural Science Foundation of China.

PMID- 10926700
TI  - A simple view of the spherical wave in dynamical theory.
AB  - The results of the Kato spherical-wave approach to the dynamical theory for
      perfect crystals are obtained by a simple and straightforward method based on the
      multiple-scattering expansion.

PMID- 10926702
TI  - International Union of Crystallography Report of the Executive Committee for
      1997.

PMID- 10926701
TI  - Solving crystal structures without Fourier mapping. I. Centrosymmetric case.
      Erratum.
AB  - Unfortunately, some printing errors escaped our attention in the proof-reading of
      our paper [Pilz & Fischer (1998). Acta Cryst. A54, 273-282]. As some of them may
      cause inconvenience or confusion to readers, they are corrected here: p. 275,
      equation (6a) should read: Q(i) = [ summation operator(j = 0)(i-1) (-1)(i-j-1)P(i
      j)Q(j)]/i. p. 277 (right column), third line after equation (12) should read:
      Using D(1) [from (10a)] ellipsis. p. 277 (right column), second line after
      equation (13) should read: ellipsis namely 2(m+n-1). p. 279 (right column), lines
      10 and 11 in second paragraph should read: ellipsis sigma(g(h)) = 0.05g(h) (or
      0.1g(h), respectively) for ellipsis. p. 279 (right column), fifth line from
      bottom should read: ellipsis example I (Table 2) ellipsis. p. 280 (right column),
      third line before Section 3.2 should read: E.g. one of them systematically
      ellipsis.

PMID- 10926703
TI  - Epidemiology of bacteriuria caused by vancomycin-resistant enterococci--a
      retrospective study.
AB  - BACKGROUND: The epidemiology of vancomycin-resistant enterococcal (VRE)
      bacteriuria has not been previously described. Our objectives are to describe the
      frequency of VRE bacteriuria, to use strict definitions to distinguish
      symptomatic urinary tract infection (UTI) versus urine colonization without
      pyuria versus asymptomatic bacteriuria with pyuria, and to describe the outcomes
      of each group. METHODS: We used a retrospective analysis of patients with VRE
      bacteriuria in an academic medical center. RESULTS: During the 18-month study
      period, 98 of the 107 patients (92%) with urine cultures positive for VRE
      (23/10,000 admissions), had charts that were available for review. In 94 of 98
      patients, the organism was Enterococcus faecium, and in only 4 was Enterococcus
      faecalis recovered. Thirty-seven patients were colonized with VRE; 21 patients
      had asymptomatic bacteriuria, and the status of 27 patients was not
      ascertainable. Thirteen patients had VRE UTIs with two associated bacteremias and
      one death. Patients with UTI versus patients without UTI were more likely to have
      an underlying malignancy (39% vs 9%, P =.014). CONCLUSION: The majority of urine
      cultures yielding VRE do not represent true infection, rather colonization or
      asymptomatic bacteriuria.

PMID- 10926704
TI  - Risk factors for acquisition of vancomycin-resistant enterococci among patients
      on a renal ward during a community hospital outbreak.
AB  - BACKGROUND: During an outbreak of vancomycin-resistant enterococcal (VRE)
      infection and colonization at a community hospital in Indianapolis, Indiana, we
      performed a case-control study of patients on the hospital's renal unit to
      determine risk factors for acquisition of VRE among this potentially high-risk
      patient population. METHODS: Twenty-four renal patients with VRE
      colonization/infection (ie, case-patients) were compared by univariate and
      multivariate analyses with 29 renal patients with nosocomially acquired
      vancomycin-susceptible enterococcal infection and colonization (ie, controls).
      RESULTS: Age and length of hospitalization were similar between the VRE case
      patients and the vancomycin-susceptible enterococcal control-patients, but case
      patients had higher Acute Physiology and Chronic Health Evaluation II scores and
      received significantly greater numbers of antimicrobials and significantly more
      days of antimicrobials during the 60 days preceding the first positive
      enterococcal culture. In an assessment of the appropriateness of vancomycin use,
      one third of vancomycin orders were found to be inappropriate in both patient
      groups. CONCLUSIONS: Our data show that among renal patients, those who are
      severely ill and receive multiple and prolonged courses of antimicrobials are at
      greatest risk for acquiring VRE infection or colonization. The Centers for
      Disease Control and Prevention recommends that hospitals develop a comprehensive
      plan to prevent and control infection and colonization of patients with VRE. This
      plan should include prompt identification of affected patients, initiation of
      isolation precautions to prevent patient-to-patient transmission of VRE, and
      prudent use of antimicrobials, including vancomycin.

PMID- 10926705
TI  - Failure of systemic antibiotics to eradicate gram-negative bacilli from the
      airway of mechanically ventilated very low-birth-weight infants.
AB  - BACKGROUND: Gram-negative bacillary (GNB) airway colonization in mechanically
      ventilated newborns is associated with morbidity and mortality, which may be
      reduced if systemic antimicrobial therapy eradicates GNB from the airway. Efforts
      to do so in adults have met with variable success; similar experiences in
      newborns have not been reported. METHODS: From 1991 through 1998, 531 very low
      birth-weight infants were mechanically ventilated longer than 2 weeks. The study
      group was 106 infants with GNB airway colonization. Sixty-four other neonates in
      whom GNB nosocomial bloodstream infections developed served as antibiotic
      treatment outcome control. RESULTS: Isolated from the airway were enteric (70
      cases) and environmental (36 cases) GNB. Gentamicin alone or with ceftazidime
      (79), ceftazidime (11), piperacillin in combination with tazobactam or tobramycin
      (8), and tobramycin, in combination with ampicillin/sulbactam or mezlocillin (8)
      were the antimicrobials selected. Systemic antibiotics failed to eradicate GNB
      colonization in 97% of the cases. Six of the 106 infants with airway colonization
      died for reasons unrelated to infection. Sixty-four infants experienced 67
      bloodstream infections as a result of enteric (53) and environmental (14) GNB.
      Gentamicin alone (23), with ceftazidime (26), or with clindamycin or
      ampicillin/sulbactam (9), piperacillin with tazobactam or tobramycin (3) and
      ceftazidime alone (6) were the antimicrobials selected. Survival occurred in 84%
      of the 67 nosocomial bloodstream infections. CONCLUSIONS: Systemic antibiotics do
      not consistently eradicate GNB from the airway of mechanically ventilated
      newborns, therefore its empirical use for prophylaxis or treatment of airway
      colonization should be discouraged.

PMID- 10926706
TI  - Prospective surveillance for antibiotic-resistant organisms in patients with
      spinal cord injury admitted to an acute rehabilitation unit.
AB  - BACKGROUND: The objective of this study was to evaluate the epidemiology of
      antibiotic-resistant organisms among patients with spinal cord injury admitted to
      an acute rehabilitation unit for the first time. METHODS: After informed consent,
      63 patients with spinal cord injury admitted to an acute rehabilitation unit
      between January 1997 and July 1998 had surveillance cultures (nares, urine,
      wounds or ulcers, and perineum) done on admission and every 2 weeks thereafter
      until discharge or as long as 6 weeks after admission. RESULTS: Of the 4
      surveillance sites, perineal cultures most commonly grew one or more potential
      pathogens; however, antibiotic-resistant organisms were most often isolated from
      wounds or ulcers and least often in urine cultures. Staphylococcus aureus
      (methicillin-sensitive plus methicillin-resistant) and enterococci represented
      44% of all organisms isolated in surveillance cultures. Methicillin-resistant S
      aureus was the most common resistant organism isolated. Less than 30% of the gram
      negative bacilli isolated were considered antibiotic-resistant strains.
      Nosocomial infection as a result of any resistant organism was infrequent. After
      adjusting for various confounding factors in a logistic regression model, only
      the presence of a pressure ulcer predicted carriage of any resistant organism on
      admission to the rehabilitation unit. Acquisition of a resistant organism after
      admission to the unit at one or more surveillance sites occurred in 8 (22%) of 36
      patients not colonized on admission. CONCLUSIONS: Methicillin-resistant S aureus
      was the most common resistant organism colonizing patients with spinal cord
      injury at the time of admission to an acute rehabilitation unit and throughout
      their stay. However, acquisition of any resistant organism after admission was
      uncommon on this unit, which used Standard Precautions in the routine care of
      patients. These findings have implications for the type of isolation procedures
      on acute rehabilitation units. The low rate of acquisition and infection with
      MRSA after admission argues against attempts at eradication as a method of
      control.

PMID- 10926707
TI  - Bacteriology and antimicrobial choice in hepatolithiasis.
AB  - BACKGROUND AND AIMS: Hepatolithiasis is prevalent in southeast Asia and presents
      a difficult management problem. Acute repeated episodes of cholangitis are
      frequently manifested in patients with hepatolithiasis. Without proper treatment,
      such infection can lead to liver abscess, secondary biliary cirrhosis, portal
      hypertension, and death from sepsis or hepatic failure. In addition to clearance
      of the stones and relief of bile stasis either by surgery or by interventional
      radiologic manipulation, effective antimicrobial therapy also plays a crucial
      role in the treatment of patients with hepatolithiasis. The aim of this study is
      to clarify the bacteriology in hepatolithiasis and to provide the information for
      an appropriate antimicrobial choice. METHODS: From July 1993 to June 1996, 150
      patients with hepatolithiasis underwent surgical intervention. Bile specimens
      were routinely obtained by syringe aspiration from common bile duct. The syringe
      was immediately capped, and the bile was subsequently cultured for both aerobes
      and anaerobes. RESULTS: Bacteria were present in the bile of all patients. The
      bacteria most frequently found were gram-negative bacteria such as Klebsiella sp,
      Escherichia coli, and Pseudomonas sp, and the gram-positive Enterococcus sp.
      Bacteroides sp were the most frequently found anaerobes. CONCLUSIONS: This study
      demonstrated the close relationship between acute cholangitis in hepatolithiasis
      and enteric bacteria and also displayed the detailed antibiotic sensitivity
      results. Armed with this fruitful information, we believe the antibiotic
      treatment for acute cholangitis in hepatolithiasis should first aim at enteric
      bacteria and be adjusted later according to the results of bacteriologic cultures
      and clinical situation to achieve an effective microbial control.

PMID- 10926708
TI  - Double-blind, randomized trial of scheduled use of a novel barrier cream and an
      oil-containing lotion for protecting the hands of health care workers.
AB  - CONTEXT: Many health care workers suffer severe hand irritation, with cracking
      and bleeding, as a consequence of frequent handwashing and glove use.
      Integumentary breakdown has major implications for nosocomial infection control
      and promotes the spread of bloodborne viruses. The potential benefits of
      scheduled use of hand-care agents-lotions or creams-in health care workers has
      not been established by controlled trial. OBJECTIVE: To compare the value of an
      oil-containing lotion with a novel barrier skin cream in health care workers with
      severe hand irritation. DESIGN: Prospective, randomized, double-blind trial.
      SETTING: University medical center. PARTICIPANTS: Fifty-four health care workers
      from multiple departments with severe hand irritation, 74% with one or more full
      thickness cracks or other integumentary breaks. MAIN OUTCOME MEASURES: Objective
      and subjective parameters for scaling, cracking, weeping, bleeding, and pain were
      scored by two blinded investigators weekly for 4 weeks, and the hands of subjects
      were cultured quantitatively at the onset and after 2 weeks and 4 weeks. RESULTS:
      Subjects in both groups experienced marked improvement in overall hand condition
      (each, P <.02), particularly in scaling, cracking, and pain. Persons randomized
      to use of the oil-containing lotion showed greater improvement (mean score, from
      6.5 to 2.7 vs 6.8 to 4. 7, P =.006). In 18 (69%) of 26 persons who used the
      control lotion, all full-thickness integumentary breaks were healed and pain was
      totally resolved, compared with 14 (52%) of 27 persons who used the barrier cream
      (P =.26). Use of the two agents in a scheduled fashion had no effect on the
      levels or profile of the transient hand flora. However, by the fourth week of
      use, handwashing frequency was 50% higher in subjects randomized to use the
      control lotion than it was in subjects randomized to use the barrier cream (17.8
      vs 11.7 times per day, P =.04). CONCLUSION: Use of an oil-containing lotion or a
      barrier cream on a scheduled basis can substantially protect the hands of
      vulnerable health care workers against drying and chemical irritation, preventing
      skin breakdown and promoting more frequent handwashing.

PMID- 10926709
TI  - Persistent contamination of fabric-covered furniture by vancomycin-resistant
      enterococci: implications for upholstery selection in hospitals.
AB  - Vancomycin-resistant enterococci (VRE) have emerged as important nosocomial
      pathogens in hospitals throughout the United States. An increasing concern with
      respect to VRE dissemination is survival on, and potential transmission from,
      environmental surfaces within health care institutions. Therefore, we assessed
      survival of VRE on fabric chairs in an attempt to determine the optimal
      upholstery for the health care setting. VRE was identified on 3 of 10 seat
      cushions sampled, including 2 chairs in a room of a patient with known VRE. After
      performing simulated contamination experiments, all samples were positive at 72
      hours and 1 week after inoculation. Contamination of the upholstery could be
      prevented by placing a sheet folded 4 times or a bath blanket folded in half on
      the seat cushion. In conclusion, VRE are capable of prolonged survival on fabric
      seat cushions and can be transferred to hands. Environmental surfaces such as
      chairs may serve as a potential reservoir for nosocomial transmission of VRE, and
      an easily cleanable, nonporous material is the preferred upholstery in hospitals.

PMID- 10926710
TI  - Statistical process control geometric Q-chart for nosocomial infection
      surveillance.
AB  - Several authors have proposed the use of statistical process control charting
      methods for the surveillance of endemic rates of nosocomial infections. The
      principal goal of such a charting program is to recognize any increase of the
      endemic rate to an epidemic rate as soon as possible after the change occurs.
      However, many of the statistical process control charting methods that have been
      proposed are based on classical charting principles that are effective largely
      for processes for which sufficient historical data are available. These methods
      require that a fairly large data set, taken while the infection rate was stable
      at a low endemic value, must be available to begin the charting process. These
      data are used both to confirm the appropriateness of the probability distribution
      and to make a control chart for the infection process based on the distribution.
      However, such data sets are often not available. The purpose of this article is
      to inform and demonstrate to readers that recent research in statistics has
      developed modern statistical process control methods that can be used effectively
      with or without such prior data. These methods make possible much more effective
      nosocomial infection surveillance programs that will give timely warnings of the
      onsets of epidemics or evidence of the effectiveness of infection control
      initiatives. These warnings will permit earlier correction initiatives and thus
      avoid much liability.

PMID- 10926711
TI  - VA's role in bioterrorism preparations.

PMID- 10926712
TI  - Re: patient hazards of needleless systems.

PMID- 10926713
TI  - Alcohol gel artifact.

PMID- 10926715
TI  - Faucet aerators: a source of patient colonization with Stenotrophomonas
      maltophilia.

PMID- 10926717
TI  - Managing waste via source reduction.

PMID- 10926718
TI  - When clusters occur: an illustrative example and a statistical dilemma.

PMID- 10926719
TI  - Environmental lead contamination and pediatric lead intoxication in an Andean
      Ecuadorian village.
AB  - Environmental lead (Pb) contamination was measured in samples of soil and locally
      grown food produce in a remote Ecuadorian village where Pb glazing of ceramics is
      the local cottage industry. The Pb concentration levels of local soil samples
      collected at varying distances from a cluster of backyard Pb baking kilns were
      29,213 ppm (microg/g) at 0.001 km, 172 ppm at 0.005 km, 81 ppm at 0.01 km, 55 ppm
      at 1 km, 19 ppm at 2 km, and 1.4 ppm at 6 km, significantly higher than levels in
      control soil samples from non-Pb-glazing reference areas. Samples of locally
      grown food produce were also found to be Pb contaminated. Venous blood samples
      from 166 schoolchildren (ages 4 months to 15 years) in the study area and 56
      children in the reference area showed mean blood lead levels of 40.0 microg/dl
      (SD: 24.5; range: 6.2. - 119.1 microg/dL) and 6.6 microg/dL (SD: 3.4; range: 1.9 
      18.1 microg/dL), respectively, which were significantly different (p = 0.0001).
      The Pb levels in milk from breastfeeding mothers ranged from 1.44 to 39 ng/g.
      Lead isotope ratios of the children's blood and of samples of village soil
      revealed a common Pb source or "fingerprint."

PMID- 10926720
TI  - Predictors of blood lead levels in agricultural villages practicing wastewater
      irrigation in Central Mexico.
AB  - To investigate whether the agricultural use of untreated wastewater (i.e. crop
      irrigation) was associated with elevated blood lead levels in a farming
      population in the Mezquital Valley and which risk factors, other than exposure to
      untreated wastewater, were associated with elevated blood lead levels, lead
      levels were measured in venous blood obtained from 735 individuals. Blood samples
      were analyzed by atomic absorption spectrophotometry. Food habits and dietary
      intake were gathered by interview, using a semi-quantitative food-frequency
      questionnaire. The average blood lead level was 7.8 microg/dL (SD 4.66 microg/dL;
      range 1.2-36.7 microg/dL). 23% of the study population had blood lead levels
      exceeding 10 microg/dL. The use of lead-glazed ceramics (LGC) was significantly
      associated with elevated lead levels (p = < 0.001). Other significant variables
      included age, gender (males), and non-farming-related occupations (e.g.,
      technicians, factory workers). p = 0.005, 0.08, and 0.001, respectively. When the
      analysis was stratified by the use of LGC for food preparation, an inverse
      relationship between higher daily calcium intake and blood lead level was
      detected (beta = - 0.040, p = < 0.05). Thus, blood lead levels were positively
      associated with the use of LGC. Calcium intake showed a protective effect, maybe
      by decreasing absorption of lead in the gastrointestinal tract. No association
      between occupational exposure to untreated wastewater or crop consumption and
      blood lead levels was detected. Further environmental and health surveillance is
      recommended.

PMID- 10926721
TI  - Re-emergence of lead poisoning from contaminated flour in a West Bank Palestinian
      village.
AB  - Although contaminated flour was first described as an important source of endemic
      lead poisoning in the Middle East almost 20 years ago, the use of lead in
      community flour mills has not been eliminated and continues to represent a
      significant environmental risk. The authors describe an outbreak of lead
      poisoning in a West Bank Palestinian family and draw attention to this unusual
      but important source of lead exposure. All 13 members of the family (two children
      and 11 adults), were found to have lead poisoning following hospitalization for
      "gastroenteritis," headache, joint pain, weight loss, and vision difficulties.
      Seven females had low hemoglobin levels. Blood lead concentrations ranged from 42
      to 84 microg/dL. Household flour samples obtained from a stone mill, previously
      closed because of lead contamination, contained 2,000 ppm lead. Flour from
      traditional stone mills reinforced with lead joints remains a potential source
      for lead poisoning.

PMID- 10926722
TI  - Cancer in radar technicians exposed to radiofrequency/microwave radiation:
      sentinel episodes.
AB  - Controversy exists concerning the health risks from exposures to
      radiofrequency/microwave irradiation (RF/MW). The authors report exposure-effect
      relationships in sentinel patients and their co-workers, who were technicians
      with high levels of exposure to RF/MW radiation. Information about exposures of
      patients with sentinel tumors was obtained from interviews, medical records, and
      technical sources. One patient was a member of a cohort of 25 workers with six
      tumors. The authors estimated relative risks for cancer in this group and latency
      periods for a larger group of self-reported individuals. Index patients with
      melanoma of the eye, testicular cancer, nasopharyngioma, non-Hodgkin's lymphoma,
      and breast cancer were in the 20-37-year age group. Information about work
      conditions suggested prolonged exposures to high levels of RF/MW radiation that
      produced risks for the entire body. Clusters involved many different types of
      tumors. Latency periods were extremely brief in index patients and a larger self
      reported group. The findings suggest that young persons exposed to high levels of
      RF/MW radiation for long periods in settings where preventive measures were lax
      were at increased risk for cancer. Very short latency periods suggest high risks
      from high-level exposures. Calculations derived from a linear model of dose
      response suggest the need to prevent exposures in the range of 10-100
      microw/cm(2).

PMID- 10926723
TI  - Cancer mortality among males in relation to exposures assessed through a job
      exposure matrix.
AB  - To identify potential associations between workplace exposures and cancer
      mortality risks, job titles collected from 1965 to 1971 for 58,678 men (a subset
      of a large representative sample of the Canadian workforce) were transformed into
      probable chemical exposures using a job-exposure matrix developed in Montreal.
      Mortality follow-up was determined through computerized record linkage with the
      National Mortality Database in Canada for 1965-1991. Cancer mortality risk was
      evaluated at two levels of exposure, any and substantial, using Poisson
      regression controlling for age, calendar period, and social class. Among the
      58,678 men, 3,160 died of cancer. Using a liberal reporting criterion, relative
      risk (RR) >1.0, five or more exposed cancer deaths, p < or = 0.100, several
      potential associations were identified, including: lung cancer and any exposure
      to abrasives dust (RR = 2.84), prostate cancer and any exposure to calcium
      carbonate (RR = 2.46), and prostate cancer and substantial exposure to metallic
      dust (RR = 2.13).

PMID- 10926724
TI  - Posttraumatic stress disorder in co-workers following exposure to a fatal
      construction accident in China.
AB  - To assess the mental disturbances induced by accidents at work, 41 male workers
      who had witnessed a fatal work accident were evaluated utilizing the criteria for
      posttraumatic stress disorder (PTSD) from the ICD-10 Classification of Mental and
      Behavioral Disorders. The Hamilton Depression Rating Scale (HDRS) was also
      administered to the exposed workers, as well as to 47 non-exposed construction
      worker controls. The two groups were well matched with respect to age, years of
      employment, and years of education. They were all of Han sect; and lifestyles,
      incomes, and living conditions were similar. The exposed workers had a high rate
      of PTSD: 11 of 41 (26.8%) at one month and five of 39 (12.9%) four months after
      the fatal accident. The exposed groups' scores for depressive symptoms were
      significantly higher than those of the controls, including: 1) depressed mood, 2)
      guilt, 3) initial insomnia, 4) middle insomnia, 5) delayed insomnia, 6) decreased
      interest in work and other activities, 7) anxiety, 8) somatization, and 9)
      gastrointestinal symptoms (p < 0.05, p < 0.01, p < 0.001). Fatal work accidents,
      a major hazard in the construction industry, affect not only the victims but also
      the mental health of other workers. PTSD and associated emotional disorders
      related to exposure to serious work accidents deserve more attention for clinical
      and research purposes.

PMID- 10926726
TI  - Silicosis and tuberculosis: a proposed radiographic classification of
      tuberculosis to accompany the ILO international classification of radiographs of
      pneumoconioses.
AB  - A significant proportion of workers exposed to silica dust are at risk of
      developing tuberculosis (TB). The higher the International Labor Organization
      (ILO) category of silicosis, the greater the TB risk. Subtle radiographic
      presentations of TB may be the initial manifestation of TB, particularly in the
      absence of sputum identification of TB bacilli. A proposed TB x-ray-reading form
      in addition to the ILO categorization of silicosis is offered. The implementation
      of a standardized TB x-ray-reading approach should alert the clinician to
      indolent TB lesions.

PMID- 10926725
TI  - Psychosocial conditions and access to an occupational health service among
      farmers.
AB  - To determine whether membership in an occupational health service program varies
      with correlation with psychosocial risk factors, this study was carried out among
      farmers in connection with a larger investigation of salutogenic factors. The
      study was based on information collected via questionnaires (answered on
      location) and standardized interviews. The material consists of 364 farmers or
      persons engaged in agriculture who had occupational health care and 548 without
      it. There were clear differences in psychosocial patterns between the groups.
      Those with occupational health care were less often single and had more education
      and more social contacts than did those without such care. Eating times were more
      regular and meals were better in those with occupational health care. Karasek
      Theorell's indices for psychological demands and decision latitude at work were
      also higher in this group. Better-educated farmers and those with larger farms
      were more often members of an occupational health care program. In addition, this
      group had fewer psychosocial risk factors.

PMID- 10926727
TI  - Selecting high-priority hazardous chemicals for tri-national control: a maximum
      utility method applied to Mexico.
AB  - The dispersion of persistent, bioaccumulative toxic chemicals poses risks to
      human health and the integrity of the ecosystem on a continental scale. Mexico,
      the United States, and Canada sought to add two pollutants to an existing list of
      four subject to North American Regional Action Plans (chlordane, DDT, mercury,
      PCBs). Mexican negotiators used results from an internal selection process,
      applying 14 criteria in five categories-physicochemical, health-endpoint, data
      quality/quantity, exposure potential, and control feasibility-to a baseline group
      of over 4,700 substances. Using policy analysis by the multiattribute maximum
      utility method, progressive application of criteria and weighting algorithms
      acted like successive filters to identify priority lists of 15 and 7
      substances/substance groups for Mexico. The 15 are: 1) benzo-a-pyrene (1 other
      PAHs); 2) cadmium; 3) heptachlor; 4) hexachlorobenzene; 5) lead; 6) lindane (+
      other HCH isomers); 7) 2,3, 7,8-tetrachlorodibenzo-p-dioxin (&plus other PCDDs);
      8) aldrin; 9) arsenic; 10) chromium; 11) carbon tetrachloride; 12) 3-3'
      dichlorobenzidine; 13) dieldrin; 14) nickel; and 15) toxaphene. The first seven
      are the priority list of seven.

PMID- 10926729
TI  - Environmental health consequences of land mines.
AB  - This article reviews the literature on the environmental effects of anti
      personnel land mines globally. Land mines represent an immediate environmental
      health problem. Between 60 and 70 million land mines are currently in place in
      over 70 countries. Designed to kill or main humans, including civilians, they
      injure an estimated 1, 200 persons and kill another 800 every week. Land-mine
      injuries tend to be serious; an estimated 300,000 persons worldwide have been
      disabled by them. The problem, politically very controversial, can be resolved
      only by preventing the further placement of mines, by demining of areas already
      mined, and by coping with the personal and environmental devastation that they
      have already caused. Environmental health personnel should be involved in
      promoting awareness of the problem, in improving services for land-mine victims,
      and in promoting political efforts to ban further use of land mines.

PMID- 10926728
TI  - Urinary excretion of hippuric acid after consumption of nonalcoholic beverages.
AB  - To investigate the types and quantities of beverages that increase urinary
      hippuric acid (HA) excretion, the authors recruited 137 healthy medical students
      and divided them into quintiles according to consumption of benzoic acid (BA) in
      beverages. Using chromatography, urinary HA before and 1.5 hours and 3 hours
      after consumption of various beverages and BA consumption in the beverages were
      measured. The mean age of the group was 24.2 years; 21 were female. The range of
      BA in 13 beverages was 0-1.02 mg/mL. The geometric means of urinary HA before
      consuming them in five groups were 0.276, 0.270, 0.207, 0.262, and 0.316 g/L,
      respectively (p = 0. 567); 1.5 hours after consuming the beverages, they were
      0.210, 0. 603, 1.026, 1.066, and 1.688 g/L, respectively, and significantly
      increased after adjustment for urinary HA before ingestion (p < 0. 001). Three
      hours after ingestion, the geometric means were 0.160, 0. 232, 0.306, 0.287, and
      0.337 g/L, respectively (p < 0.001). The authors estimate that beverages that
      contain more than 100 mg BA could increase urinary HA excretion significantly, up
      to 1.12 g/L without toluene exposure. Checking dietary and beverage-intake
      histories is essential in the interpretation of urinary HA concentrations in
      population studies.

PMID- 10926730
TI  - Liability of multinational corporations: a crucial issue.

PMID- 10926731
TI  - Lead mining must be stopped.

PMID- 10926732
TI  - Rebuttal from the Health and Safety Executive.

PMID- 10926733
TI  - Topical cidofovir: a novel treatment for recalcitrant molluscum contagiosum in
      children infected with human immunodeficiency virus 1.

PMID- 10926734
TI  - Green tea and skin.
AB  - OBJECTIVE: To discuss the current knowledge of polyphenolic compounds present in
      green tea as anti-inflammatory, antioxidant, and anticarcinogenic in skin. DATA
      SOURCES: References identified from bibliographies of pertinent articles,
      including our work in related fields. STUDY SELECTION AND DATA EXTRACTION:
      Articles were selected based on the use of green tea or its polyphenolic
      constituents for prevention against inflammation and cancer in the skin. Also
      discussed is the possible use of green tea to treat various inflammatory
      dermatoses. DATA SYNTHESIS: The polyphenolic compounds from green tea were tested
      against chemical carcinogenesis and photocarcinogenesis in murine skin. These
      green tea polyphenols were found to afford protection against chemical
      carcinogenesis as well as photocarcinogenesis in mouse skin. A few experimental
      studies were conducted in human skin in our laboratory. Analysis of published
      studies demonstrates that green tea polyphenols have anti-inflammatory and
      anticarcinogenic properties. These effects appear to correlate with antioxidant
      properties of green tea polyphenols. CONCLUSIONS: The outcome of the several
      experimental studies suggests that green tea possess anti-inflammatory and
      anticarcinogenic potential, which can be exploited against a variety of skin
      disorders. Although more clinical studies are needed, supplementation of skin
      care products with green tea may have a profound impact on various skin disorders
      in the years to come. Arch Dermatol. 2000;136:989-994

PMID- 10926735
TI  - Safety and efficacy of 1 year of tacrolimus ointment monotherapy in adults with
      atopic dermatitis. The European Tacrolimus Ointment Study Group.
AB  - OBJECTIVE: To investigate the safety and efficacy of using 0.1% tacrolimus
      ointment for long-term treatment of atopic dermatitis. DESIGN: Open-label,
      noncomparative study with 6 to 12 months of follow-up. SETTINGS: Outpatient
      departments in 30 study centers in 11 European countries. PATIENTS: We enrolled
      316 patients aged 18 years and older with moderate to severe atopic dermatitis,
      200 for 6 months and 116 for 12 months; 77.5% of patients completed the study.
      INTERVENTION: Twice-daily application of 0.1% tacrolimus ointment on all affected
      skin. Visits were scheduled on day 1; after 1, 2, and 4 weeks of treatment; and
      monthly thereafter. MAIN OUTCOME MEASURES: Safety assessments included monitoring
      of adverse events, clinical laboratory values, and tacrolimus blood
      concentrations. Efficacy end points included a combined score (modified Eczema
      Area and Severity Index) and an investigator's global assessment. RESULTS: Local
      irritation, adverse events such as burning sensation (47% of patients), pruritus
      (24% of patients), and erythema (12% of patients) were common but tended to occur
      only when initiating treatment. Laboratory values showed no marked changes over
      time. Systemic absorption was minimal, with the maximum tacrolimus blood
      concentration being less than 1 ng/mL in 76% of patients. All efficacy end points
      showed improvement. The mean (SD) modified Eczema Area and Severity Index score
      was 23.7 (12.6) at day 1, 13.5 (11.3) at week 1, 6.1 (9.2) at month 6, and 6.1
      (8.1) at month 12. Marked or excellent improvement or clearance of disease was
      reported in 54%, 81%, and 86% of patients at week 1, month 6, and month 12,
      respectively. CONCLUSION: Up to 1 year of tacrolimus ointment use was safe and
      effective in patients with atopic dermatitis. Arch Dermatol. 2000;136:999-1006

PMID- 10926736
TI  - Therapeutic ionizing radiation and the incidence of basal cell carcinoma and
      squamous cell carcinoma. The New Hampshire Skin Cancer Study Group.
AB  - OBJECTIVE: To estimate the relative risk of developing basal cell carcinoma (BCC)
      and squamous cell carcinoma (SCC) after receiving therapeutic ionizing radiation.
      DESIGN: Population-based case-control study. SETTING: New Hampshire. PATIENTS: A
      total of 592 cases of BCC and 289 cases of SCC identified through a statewide
      surveillance system and 536 age- and sex-matched controls selected from
      population lists. MAIN OUTCOME MEASURES: Histologically confirmed BCC and
      invasive SCC diagnosed between July 1, 1993, through June 30, 1995, among New
      Hampshire residents. RESULTS: Information regarding radiotherapy and other
      factors was obtained through personal interviews. An attempt was made to review
      the radiation treatment records of subjects who reported a history of
      radiotherapy. Overall, an increased risk of both BCC and SCC was found in
      relation to therapeutic ionizing radiation. Elevated risks were confined to the
      site of radiation exposure (BCC odds ratio, 3. 30; 95% confidence interval, 1.60
      6.81; SCC odds ratio, 2.94; 95% confidence interval, 1.30-6.67) and were most
      pronounced for those irradiated for acne exposure. For SCC, an association with
      radiotherapy was observed only among those whose skin was likely to sunburn with
      sun exposure. CONCLUSIONS: These results largely agree with those of previous
      studies on the risk of BCC in relation to ionizing radiation exposure. In
      addition, they suggest that the risk of SCC may be increased by radiotherapy,
      especially in individuals prone to sunburn with sun exposure. Arch Dermatol.
      2000;136:1007-1011

PMID- 10926737
TI  - Surface microscopy of pigmented basal cell carcinoma.
AB  - OBJECTIVES: To describe the relevant morphologic features and to create a simple
      diagnostic method for pigmented basal cell carcinoma (BCC) using in vivo
      cutaneous surface microscopy (ie, dermoscopy, dermatoscopy, or oil
      epiluminescence microscopy). DESIGN: Pigmented skin lesions were photographed in
      vivo using immersion oil (surface microscopy). All pigmented skin lesions were
      excised and reviewed for histological diagnosis. Photographs of 142 pigmented
      BCCs, 142 invasive melanomas, and 142 benign pigmented skin lesions were randomly
      divided into 2 equally sized training and test sets. Images from the training set
      were scored for 45 surface microscopy features. From this a model was derived and
      tested on the independent test set. SETTING: All patients were recruited from the
      primary case and referral centers of the Sydney Melanoma Unit, Sydney, Australia,
      and the Skin and Cancer Unit, Skin and Cancer Associates, Plantation, Fla.
      PATIENTS: A random sample (selected from a larger database) of patients whose
      lesions were excised. MAIN OUTCOME MEASURES: Sensitivity and specificity of the
      model for diagnosis of pigmented BCCs. RESULTS: The following model was created.
      For a pigmented BCC to be diagnosed it must not have the negative feature of a
      pigment network and must have 1 or more of the following 6 positive features:
      large gray-blue ovoid nests, multiple gray-blue globules, maple leaflike areas,
      spoke wheel areas, ulceration, and arborizing "treelike" telangiectasia. On an
      independent test set the model had a sensitivity of 97% for the diagnosis of
      pigmented BCCs and a specificity of 93% for the invasive melanoma set and 92% for
      the benign pigmented skin lesion set. CONCLUSION: A robust surface microscopy
      method is described that allows the diagnosis of pigmented BCCs from invasive
      melanomas and benign pigmented skin lesions. Arch Dermatol. 2000;136:1012-1016

PMID- 10926738
TI  - Further evidence for an association of HLA-DR7 with basal cell carcinoma on the
      tropical island of Saba.
AB  - OBJECTIVE: To establish the association of HLA alleles (ie, HLA-DR1, HLA-DR4, and
      HLA-DR7) with individuals with skin cancer on the tropical island of Saba. This
      island was chosen because most of the white population has fair skin and
      excessive exposure to sunlight, which results in a high prevalence of skin
      cancer. DESIGN: HLA typing was performed in 124 white individuals with
      histologically proven basal cell and/or squamous cell carcinoma and in control
      subjects. Skin type, the presence of freckling, and the number of actinic
      keratoses were determined. SETTING: Population-based study. SUBJECTS: Inhabitants
      of Saba with and without skin cancer. MAIN OUTCOME MEASURE: Presence of HLA-DR1,
      HLA-DR4, and HLA-DR7 alleles. RESULTS: Associations of HLA alleles with basal
      cell and squamous cell carcinoma have been reported. The presence of the HLA-DR7
      allele was positively associated with the development of basal cell carcinoma
      (odds ratio, 3.8; 95% confidence interval, 1.1-13.4). Adjustment for skin type,
      which is a potentially confounding factor for the association between HLA alleles
      and skin cancer, did not substantially alter this association. No other
      associations between HLA alleles and skin cancer were found, possibly because of
      the small size of the study population. CONCLUSION: This study presented further
      evidence for an association between HLA-DR7 and basal cell carcinoma. Arch
      Dermatol. 2000;136:1019-1022

PMID- 10926739
TI  - gamma delta T-cell lymphoma of the skin: a clinical, microscopic, and molecular
      study.
AB  - BACKGROUND: Only a few cases of primary gamma delta cutaneous T-cell lymphoma
      (CTCL) have been reported. We encountered 3 cases of this rare condition.
      OBJECTIVES: To characterize gamma delta CTCL by clinical, microscopic, and
      molecular methods and to investigate the role of Epstein-Barr virus (EBV)
      infection in its pathogenesis. DESIGN: Patients were evaluated by clinical
      examination, and biopsy specimens of lesional skin were examined by light
      microscopy and immunohistochemistry. Polymerase chain reaction amplification for
      T-cell receptor gamma gene rearrangements and in situ hybridization for EBV were
      performed on 3 biopsy specimens. SETTING: National Institutes of Health, a
      tertiary referral center. PATIENTS: Individuals with a clinical and histologic
      diagnosis of primary gamma delta CTCL. OUTCOME MEASURES: Clinical, light
      microscopic, and immunohistochemical features, and the presence of T-cell
      rearrangement and EBV RNA in biopsy specimens. RESULTS: Patients exhibited
      multiple plaques, tumors, and/or subcutaneous nodules primarily distributed over
      the extremities. Individuals exhibited an aggressive clinical course with
      resistance to multiagent chemotherapy and radiation. Microscopic examination
      revealed epidermotropism in 2 cases, a dermal infiltrate in all 3 cases, and
      subcutaneous involvement in 1 case. Immunohistochemical studies showed the
      presence of CD3(+)TCR delta(+) in 3 patients, CD8(+)in 1, and CD4(+), CD20(+),
      CD56(+), and beta F1(+) in none. All 3 cases exhibited an activated cytotoxic T
      cell phenotype positive for T-cell intracellular antigen 1, perforin, and
      granzyme B. A clonal T-cell receptor gamma chain gene rearrangement was detected
      in all 3 cases by polymerase chain reaction. In situ hybridization was negative
      for EBV sequences in all 3 cases. CONCLUSION: gamma delta Cutaneous T-cell
      lymphomas are EBV-negative lymphomas that express a mature cytotoxic phenotype
      and have an aggressive clinical behavior. Arch Dermatol. 2000;136:1024-1032

PMID- 10926740
TI  - Lupus erythematosus tumidus--a neglected subset of cutaneous Lupus erythematosus:
      report of 40 cases.
AB  - BACKGROUND: Lupus erythematosus tumidus (LET) is characterized clinically by
      erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas.
      Results of histological examination show perivascular and periadnexal lymphocytic
      infiltration and interstitial mucin deposition. The main differential diagnoses
      are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin,
      reticular erythematous mucinosis, and pseudolymphoma. Since its first description
      in 1930, LET has been documented rarely in the literature, and its clinical
      importance has not been fully appreciated. OBSERVATIONS: We characterized 40
      patients with clinical and histological features of LET observed at our
      department from 1984 through 1998. The onset of the disease clustered in summer
      because of sun exposure, and 28 (70%) of the patients showed a remarkable
      photosensitivity confirmed by results of provocative phototesting. A complete
      resolution of the skin lesions was seen after systemic therapy with antimalarials
      and, in some cases, with local corticosteroids or spontaneously without any
      treatment. In 4 (10%) of the patients, antinuclear antibodies were detected;
      however, there was no evidence of underlying systemic involvement in any of the
      patients. CONCLUSIONS: Our data constitute the largest number of patients with
      LET collected until now. The clinical picture, extreme photosensitivity,
      histological findings, and effective treatment with antimalarials are so
      characteristic that LET should be considered as a separate entity and
      differentiated from other variants of cutaneous LE. Arch Dermatol. 2000;136:1033
      1041

PMID- 10926741
TI  - Questions answered and a $1 million question raised concerning lupus
      erythematosus tumidus: is routine laboratory surveillance testing during
      treatment with hydroxychloroquine for skin disease really necessary.

PMID- 10926742
TI  - Green tea: what's brewing?

PMID- 10926743
TI  - Cutaneous gamma delta T-cell lymphomas--how and why should they be recognized?

PMID- 10926744
TI  - Recurrent pustular rash in a pregnant woman.

PMID- 10926746
TI  - Multiple unilateral persistent pigmented patches on the lower extremities.

PMID- 10926745
TI  - A generalized itchy flexural eruption in a 7-year-old boy.

PMID- 10926747
TI  - Widespread pea-sized papules and gooseflesh plaques in a 44-year-old woman.

PMID- 10926748
TI  - Terminology in dermatology: logical or arbitrary?

PMID- 10926749
TI  - Contact allergy from temporary tattoos.

PMID- 10926750
TI  - Long-term efficacy of tacrolimus ointment for recalcitrant facial erythema
      resistant to topical corticosteroids in adult patients with atopic dermatitis.

PMID- 10926751
TI  - Pregnancy and Behcet disease.

PMID- 10926752
TI  - Curly hair and lipodystrophy as a result of highly active antiretroviral
      treatment?

PMID- 10926753
TI  - The involvement of axonin-1/SC2 in mediating notochord-derived chemorepulsive
      activities for dorsal root ganglion neurites.
AB  - Previous studies have suggested that the developing notochord secretes diffusible
      axon guidance molecules that repel dorsal root ganglion (DRG) neurites (R. Keynes
      et al., 1997, Neuron 18, 889-897; K. Nakamoto and T. Shiga, 1998, Dev. Biol. 202,
      304-314). Neither notochord-derived chemorepellents nor their receptors on DRG
      neurites are, however, known. Here we investigated whether cell adhesion
      molecules (CAMs) of the immunoglobulin/fibronectin type III subfamily present on
      DRG neurites, including axonin-1/SC2, N-CAM, Ng-CAM, and Nr-CAM, are required for
      mediating the notochord-derived chemorepulsion. Using collagen gel cocultures of
      DRGs and notochord explants, we found that an antibody against axonin-1/SC2
      diminished the effects of the chemorepulsive activity from the notochord, whereas
      antibodies against N-CAM, Ng-CAM, and Nr-CAM had no effect. We further showed
      that the removal of glycosylphosphatidylinositol-anchored cell surface molecules,
      including axonin-1/SC2, from DRG neurites diminished the effects of the notochord
      derived chemorepulsive activity to an extent similar to that of treatment with
      the anti-axonin-1/SC2 antibody. These results suggest that axonin-1/SC2 expressed
      on DRG neurites may be involved in mediating the notochord-derived chemorepulsive
      activity.

PMID- 10926754
TI  - MyoD(-/-) satellite cells in single-fiber culture are differentiation defective
      and MRF4 deficient.
AB  - MyoD-deficient mice are without obvious deleterious muscle phenotype during
      embryogenesis and fetal development, and adults in the laboratory have grossly
      normal skeletal muscle and life span. However, a previous study showed that in
      the context of muscle degeneration on a mdx (dystrophin null) genetic background,
      animals lacking MyoD have a greatly intensified disease phenotype leading to
      lethality not otherwise seen in mdx mice. Here we have examined MyoD(-/-) adult
      muscle fibers and their associated satellite cells in single myofiber cultures
      and describe major phenotypic differences found at the tissue, cellular, and
      molecular levels. The steady-state number of satellite cells on freshly isolated
      MyoD(-/-) fibers was elevated and abnormal branched fiber morphologies were
      observed, the latter suggesting chronic muscle regeneration in vivo. Single-cell
      RNA coexpression analyses were performed for c-met, m-cadherin, and the four
      myogenic regulatory factors (MRFs.) Most mutant satellite cells entered the cell
      cycle and upregulated expression of myf5, both characteristic early steps in
      satellite cell maturation. However, they later failed to normally upregulate
      MRF4, displayed a major deficit in m-cadherin expression, and showed a
      significant diminution in myogenin-positive status compared with wildtype. MyoD(
      /-) satellite cells formed unusual aggregate structures, failed to fuse
      efficiently, and showed greater than 90% reduction in differentiation efficiency
      relative to wildtype. A further survey of RNAs encoding regulators of growth and
      differentiation, cell cycle progression, and cell signaling revealed similar or
      identical expression profiles for most genes as well as several noteworthy
      differences. Among these, GDF8 and Msx1 were identified as potentially important
      regulators of the quiescent state whose expression profile differs between mutant
      and wildtype. Considered together, these data suggest that activated MyoD(-/-)
      satellite cells assume a phenotype that resembles in some ways a developmentally
      "stalled" cell compared to wildtype. However, the MyoD(-/-) cells are not merely
      developmentally immature, as they also display novel molecular and cellular
      characteristics that differ from any observed in wild-type muscle precursor
      counterparts of any stage.

PMID- 10926755
TI  - Embryonic origins of auditory brain-stem nuclei in the chick hindbrain.
AB  - The auditory nuclei of the chick brain stem have distinct morphologies and highly
      specific synaptic connectivity. Nucleus magnocellularis (NM) and nucleus
      angularis receive tonotopically ordered cochlear input. NM in turn projects
      tonotopically to nucleus laminaris (NL), maintaining binaural specificity with
      projections to either dorsal or ventral NL dendrites. NM and NL arise from a
      common anlage, which differentiates as the cells migrate and acquire their mature
      morphologies. NM and NL cells are closely associated during embryogenesis and
      synapse formation. However, the morphologies of the nuclei and of the cells
      within the nuclei differ greatly between NM and NL. While later maturation of
      these nuclei has been described in considerable detail, relatively little is
      known about the early embryonic events that lead to the formation of these
      nuclei. We examined the embryonic origins of cells in brain-stem auditory nuclei
      with particular emphasis on NM and NL. Lipophilic dyes were injected into small
      regions of the embryonic hindbrain prior to the birth and migration of cells that
      contribute to these nuclei. We found that NM arises from rhombomeres r5, r6, and
      r7, and NL arises mostly from r5 with a few cells arising from r6. NM and NL thus
      have partially overlapping rhombomeres of origin. However, we found that the
      precursors for NM and NL are found in distinct regions within rhombomere 5, with
      NM precursors in medial regions and NL precursors in lateral regions. Our results
      do not support a lineage relationship between NM and NL cells and they suggest
      that NM and NL are specified prior to migration of precursors to the auditory
      anlage.

PMID- 10926756
TI  - Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing
      coreceptor MAdCAM-1 in specialized endothelial cells of the viscera.
AB  - Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid
      organ development, immune surveillance, and inflammatory responses. We report
      here that mice deficient in the homeobox gene Nkx2-3, expressed in developing
      visceral mesoderm, show a complex intestinal malabsorption phenotype and striking
      abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged
      leukocyte homing. Mutant Peyer's patches were reduced in number and size,
      intestinal villi contained few IgA(+) plasma cells, and mutant spleens were small
      and often atrophic, showing fused periarterial lymphoid sheaths, partially merged
      T and B cell zones, an absent marginal zone, and a dearth of macrophages in red
      pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down
      regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in
      endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of
      the immunoglobulin superfamily, acting as an endothelial cell ligand for
      leukocyte homing receptors L-selectin and alpha4beta7 integrin. Our data suggest
      a role for a homeodomain factor in establishing the developmental and positional
      cues in endothelia that regulate leukocyte homing through local control of
      cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3.

PMID- 10926757
TI  - Genes expressed in the amphioxus notochord revealed by EST analysis.
AB  - The notochord cell of the cephalochordate amphioxus adult is unique due to the
      occurrence of myofilaments in the cytoplasm. The present EST (expressed sequence
      tag) analysis targeted mRNAs of the amphioxus notochord to determine genes that
      are expressed there. Notochord cells were isolated from Branchiostoma belcheri
      adults, from which a cDNA library was constructed. Analysis of a set of 257 ESTs
      (both 5' and 3' ends) showed that about 11% of the cDNAs are related to muscle
      genes, while 9% of them are genes for extracellular matrix proteins associated
      with formation of the notochordal sheath. The muscle-related genes included
      actin, tropomyosin, troponin I, myosin regulatory light chain, myosin light chain
      kinase, myosin heavy chain, calmodulin, calponin, calcium vector protein,
      creatine kinase, muscle LIM protein, and SH3-binding glutamate-rich protein,
      suggesting that vertebrate skeletal and smooth muscle-type genes are
      simultaneously expressed in the amphioxus notochord. Nucleotide sequences of
      cDNAs for actin, tropomyosin, troponin I, and a few others were completely
      determined to substantiate the conclusions. The chordate muscle-type actin is
      distinguishable from the cytoplasmic-type actin by the usage of amino acid
      residues at 20 diagnostic positions. Interestingly, analysis of the usage of
      amino acid residues at these positions showed that the "amphioxus notochord
      actin" is a unique intermediate between muscle-type and cytoplasmic-type actins.
      These results strongly suggest that the notochord of adult amphioxus is a
      mechanical swimming organ and its role is quite different from the role of the
      vertebrate embryonic notochord, which functions as a source of signals required
      for body plan formation.

PMID- 10926758
TI  - VEGF regulates cell behavior during vasculogenesis.
AB  - Prominent among molecules that control neovascular processes is vascular
      endothelial growth factor (VEGF). The VEGF ligands comprise a family of well
      studied mitogens/permeability factors that bind cell surface receptor tyrosine
      kinases. Targets include VEGF receptor-1/Flt1 and VEGF receptor-2/Flk1. Mice
      lacking genes for VEGF ligand or VEGF receptor-2 die early in gestation, making
      it difficult to determine the precise nature of underlying endothelial cellular
      behavior(s). To examine the effect(s) of VEGF signaling on cell behavior in
      detail, we conducted loss-of-function studies using avian embryos. Injection of
      soluble VEGFR-1 results in malformed vascular networks and the absence of large
      vessels. In the most severe cases embryos exhibited vascular atresia. Closely
      associated with the altered phenotype was a clear endothelial cell response-a
      marked decrease in cell protrusive activity. Further, we demonstrate that VEGF
      gain of function strikingly increased cell protrusive activity. Together, our
      data show that VEGF/VEGF receptor signaling regulates endothelial cell protrusive
      activity, a key determinant of blood vessel morphogenesis. We propose that VEGF
      functions as an instructive molecule during de novo blood vessel morphogenesis.

PMID- 10926759
TI  - IGFs, insulin, Shh, bFGF, and TGF-beta1 interact synergistically to promote
      somite myogenesis in vitro.
AB  - Studies from our group and others have shown that in vitro somite myogenesis is
      regulated by neural tube and notochord factors including Wnt, Sonic hedgehog
      (Shh), and basic fibroblast growth factor (bFGF) together with transforming
      growth factor-beta1 (TGF-beta1). In this study we report that insulin and insulin
      like growth factors I and II (IGF-I and -II) also promote myogenesis in explant
      cultures containing single somites or somite-sized pieces of segmental plate
      mesoderm from 2-day (stage 10-14) chicken embryos and that the combination of
      insulin/IGFs with bFGF plus TGF-beta1 promotes even higher levels of myogenesis.
      We also found that Shh promotes myogenesis in this in vitro system and that Shh
      interacts synergistically with insulin/IGFs to promote high levels of myogenesis.
      RT-PCR analysis detected insulin, IGF-II, insulin receptor, and IGF receptor
      mRNAs in both the neural tube and the somites, whereas IGF-I transcripts were
      detected in entire embryos but not in the neural tube or somites. Treatment of
      somite-neural tube cocultures with anti-insulin, anti-IGF-II, anti-insulin
      receptor, or anti-IGF receptor blocking antibodies caused a significant decrease
      in myogenesis. These results are consistent with the hypothesis that systemic IGF
      I as well as insulin and IGF-II secreted by the neural tube act as additional
      early myogenic signals during embryogenesis. Further studies indicate that
      insulin, IGFs, bFGF, and Shh also stimulate somite cell proliferation and
      influence apoptosis.

PMID- 10926760
TI  - Tracing the progeny of the aortic hemangioblast in the avian embryo.
AB  - A population of hematopoietic progenitors becomes committed within the embryo
      proper in the floor of the aorta (P-Sp/AGM in the mouse). In birds, this first
      aspect of intraembryonic hematopoiesis is prominent during embryonic day 3 (E3)
      as endothelium-associated "intra-aortic clusters." Between E6 and E8, diffuse
      hematopoiesis then occurs as "para-aortic foci" located in the dorsal mesentery
      ventral to the aorta. These foci are not associated with endothelium. Whether
      these two hematopoietic cell populations arise from distinct or common
      progenitors is not known. We could recently trace back the origin of intra-aortic
      clusters in the avian embryo by labeling aortic endothelial cells (EC) in vivo
      with acetylated low-density lipoproteins. This approach established the
      derivation of early intraembryonic hemopoietic cells from the endothelium, but
      did not indicate how long during ontogeny such a relationship may exist, since
      the progeny of EC labeled at E2 could be traced for 1-2 days at most. Here we
      report that, when E2 aortic ECs were infected prior to the formation of intra
      aortic clusters with a nonreplicative LacZ-bearing retroviral vector, numerous
      cells were labeled in the para-aortic foci at E6. In contrast, when the
      retroviral vector was inoculated at E4 rather than E2, that is, after the
      disappearance of intra-aortic clusters, no cells in the para-aortic foci were
      labeled. Taken together, our results demonstrate that ECs from the aortic floor
      seed the two aspects of aorta-associated hemopoiesis and that these ECs with
      hemangioblastic potential are present only transiently in the aorta.

PMID- 10926761
TI  - Relationship between gene expression domains of Xsnail, Xslug, and Xtwist and
      cell movement in the prospective neural crest of Xenopus.
AB  - The markers Xslug, Xsnail, and Xtwist all are expressed in the presumptive neural
      folds and are thought to delineate the presumptive neural crest. However, their
      interrelationship and relative spatiotemporal distributions are not well
      understood. Here, we present a detailed in situ hybridization analysis of the
      relative patterns of expression of these transcription factors from gastrulation
      through neurulation and post-neural crest migration. The three genes mark the
      prospective neural crest and roof plate, coming on sequentially, with Xsnail
      preceding Xslug preceding Xtwist. By combining gene expression analysis with a
      fate map of the same region using DiI labeling, we determined the correspondence
      between early and late domains of gene expression. At the beginning of
      gastrulation, Xsnail is present in a unique domain of expression in a lateral
      region of the embryo in both superficial and deep layers of the ectoderm, as are
      Xslug and Xtwist. During gastrulation and neurulation, the superficial layer
      moves faster toward the dorsal midline than the deep layer, producing a relative
      shift in these cell populations. By early neurula stage, the Xsnail domain is
      split into a medial domain in the superficial ectoderm (fated to become the roof
      plate) and a lateral domain in the deep layer of the ectoderm (fated to become
      neural crest). Xsnail is down-regulated in the most anterior neural plate and up
      regulated in the posterior neural plate. Our results show that changes in the
      expression of Xsnail, Xslug, and Xtwist are a consequence of active cell movement
      in some regions coupled with dynamic changes in gene expression in other regions.

PMID- 10926762
TI  - BMP signaling is required for heart formation in vertebrates.
AB  - In these studies, we have taken advantage of a transient transgenic strategy in
      Xenopus embryos to demonstrate that BMP signaling is required in vivo for heart
      formation in vertebrates. Ectopic expression of dominant negative Type I (tALK3)
      or Type II (tBMPRII) BMP receptors in developing Xenopus embryos results in
      reduction or absence of heart formation. Additionally, blocking BMP signaling in
      this manner downregulates expression of XNkx2-5, a homeobox gene required for
      cardiac specification, prior to differentiation. Notably, however, initial
      expression of XNkx2-5 is not affected. Mutant phenotypes can be rescued by co
      injection of mutant with wild-type receptors or co-injection of mutant receptors
      with XSmad1, a downstream mediator of BMP signaling. Whole-mount in situ analyses
      indicate that ALK3 and XSmad1 are coexpressed in cardiogenic regions. Together,
      our results demonstrate that BMP signaling is required for maintenance of XNkx2-5
      expression and heart formation and suggest that ALK3, BMPRII, and XSmad1 may
      mediate this signaling.

PMID- 10926763
TI  - Altered retinoic acid sensitivity and temporal expression of Hox genes in
      polycomb-M33-deficient mice.
AB  - The Polycomb group genes are required for the correct expression of the homeotic
      complex genes and segment specification during Drosophila embryogenesis and
      larval development. In mouse, inactivation studies of several Polycomb group
      genes indicate that they are also involved in Hox gene regulation. We have used
      our previously generated M33 mutants to study the function of M33, the mouse
      homologue of the Polycomb gene of Drosophila. In this paper, we show that in the
      absence of M33, the window of Hoxd4 retinoic acid (RA) responsiveness is opened
      earlier and that Hoxd11 gene expression is activated earlier in development This
      indicates that M33 antagonizes the RA pathway and has a function in the
      establishment of the early temporal sequence of activation of Hox genes. Despite
      the early activation, A-P boundaries are correct in later stages, indicating a
      separate control mechanism for early aspects of Hox regulation. This raises a
      number of interesting issues with respect to the roles of both Pc-G proteins and
      Hox regulatory mechanisms. We propose that a function of the M33 protein is to
      control the accessibility of retinoic acid response elements in the vicinity of
      Hox genes regulatory regions by direct or indirect mechanisms or both. This could
      provide a means for preventing ectopic transactivation early in development and
      be part of the molecular basis for temporal colinearity of Hox gene expression.

PMID- 10926764
TI  - Local inhibition of cortical rotation in Xenopus eggs by an anti-KRP antibody.
AB  - The dorsal-ventral axis of amphibian embryos is specified by the "cortical
      rotation," a translocation of the egg cortex relative to the vegetal yolk mass.
      The mechanism of cortical rotation is not understood but is thought to involve an
      array of aligned, commonly oriented microtubules. We have demonstrated an
      essential requirement for kinesin-related proteins (KRPs) in the cortical
      rotation by microinjection beneath the vegetal cortex of an antipeptide antibody
      recognising multiple Xenopus egg KRPs. Time-lapse videomicroscopy revealed a
      striking local inhibition of the cortical rotation around the injection site,
      indicating that KRP-mediated translocation of the cortex is generated by forces
      acting across the vegetal subcortical region. Anti-tubulin immunofluorescence
      showed that the antibody disrupted both formation and maintenance of the aligned
      microtubule array. Direct examination of rhodamine-labelled microtubules by
      confocal microscopy showed that the anti-KRP antibody provoked striking three
      dimensional flailing movement of the subcortical microtubules. In contrast,
      microtubules in antibody-free regions undulated only within the plane of the
      cortex, a significant population exhibiting little or no net movement. These
      findings suggest that KRPs have a critical role during cortical rotation in
      tethering microtubules to the cortex and that they may not contribute
      significantly to the translocation force as previously thought.

PMID- 10926765
TI  - Patterning the embryonic heart: identification of five mouse Iroquois homeobox
      genes in the developing heart.
AB  - We isolated cDNAs of mouse Iroquois-related homeobox genes Irx1, -2, -3, -4, and 
      5 and characterized their patterns of expression in the developing heart. Irx1
      and Irx2 were found to be expressed specifically in the ventricular septum from
      the onset of its formation onward. In fetal stages, the expression of both genes
      appeared to gradually become confined to the myocardium of the atrioventricular
      bundle and bundle branches of the forming ventricular conduction system. Irx3 was
      found to be expressed specifically in the trabeculated myocardium of the
      ventricles. Irx4 expression was observed in a segment of the linear heart tube
      and the atrioventricular canal and ventricular myocardium including the inner
      curvature after looping, resembling the pattern of MLC2V. Transcripts for Irx5
      were detected specifically in the endocardium lining the ventricular and atrial
      working myocardium that also expressed von Willebrand factor, but were absent
      from the endocardium of the endocardial cushions, i.e., the atrioventricular
      canal, inner curvature, and outflow tract. The spatiodevelopmental pattern of
      Irx5 matched that of ANF, a marker for the forming working myocardium of the
      chambers. Taken together, all members of the Irx gene family were found to be
      expressed in highly specific patterns in the developing mouse heart, suggesting a
      critical role in the specification of the distinct components of the four
      chambered heart.

PMID- 10926766
TI  - Patterning the early zebrafish by the opposing actions of bozozok and vox/vent.
AB  - Fish and frog embryos are patterned along the dorsal-ventral axis during the
      gastrula stage by opposing gradients of Bmps and Bmp inhibitory proteins. Three
      transcriptional repressors with partially overlapping expression domains have
      been proposed to be important mediators of Bmp function in Xenopus. We find that
      two related factors are expressed in the early zebrafish embryo. Although these
      factors are considerably divergent from the related Xenopus genes, they are
      expressed in domains similar to those of their Xenopus relatives throughout
      embryogenesis. Both of the zebrafish genes, which we have named vox and vent, are
      potent ventralizing factors in both zebrafish and Xenopus embryos. Using mutants
      in the Bmp pathway, we find that there are Bmp-dependent and Bmp-independent
      domains of vox expression, whereas vent is mostly dependent upon Bmp signaling.
      We show that ectopic vox or vent negatively regulates expression of the early
      dorsal gene bozozok (boz) and that ectopic boz eliminates vox and vent
      expression. Moreover, the normal exclusion of vox and vent from the organizer
      region is lost in boz mutant embryos. Our results show that boz and vox/vent are
      mutually antagonistic and indicate that the early establishment of the size of
      the organizer domain is dependent on an interplay between these early expressed
      transcriptional repressors.

PMID- 10926767
TI  - Lemon encodes an unusual receptor protein-tyrosine kinase expressed during
      gametogenesis in Hydra.
AB  - In a screen for receptor protein-tyrosine kinase (RTK) genes expressed during
      gametogenesis in the cnidarian Hydra vulgaris, we isolated a cDNA encoding Lemon,
      an RTK with unusual features. Lemon is orthologous to Drosophila Dtrk, chicken
      Klg, and human colon carcinoma kinase-4. These genes constitute an RTK class
      characterized by a conserved transmembrane sequence, the presence of
      extracellular immunoglobulin-like repeats, and the absence of the DFG motif in
      the kinase domain. We provide evidence that Lemon is a component of an unusual
      RTK signal transduction mechanism that may involve transmembrane domain-mediated
      interactions and may not be dependent on its own catalytic activity. Lemon
      transcription is dynamically regulated in interstitial cells during asexual
      budding and gametogenesis. Transcriptional up-regulation occurs early in
      spermatogenesis and oogenesis concurrent with the local accumulation of
      interstitial cells in the body column of sexual polyps.

PMID- 10926768
TI  - Disruption of gastrulation and heparan sulfate biosynthesis in EXT1-deficient
      mice.
AB  - Mutations in the EXT1 gene are responsible for human hereditary multiple
      exostosis type 1. The Drosophila EXT1 homologue, tout-velu, regulates Hedgehog
      diffusion and signaling, which play an important role in tissue patterning during
      both invertebrate and vertebrate development. The EXT1 protein is also required
      for the biosynthesis of heparan sulfate glycosaminoglycans that bind Hedgehog. In
      this study, we generated EXT1-deficient mice by gene targeting. EXT1 homozygous
      mutants fail to gastrulate and generally lack organized mesoderm and
      extraembryonic tissues, resulting in smaller embryos compared to normal
      littermates. RT-PCR analysis of markers for visceral endoderm and mesoderm
      development indicates the delayed and abnormal development of both of these
      tissues. Immunohistochemical staining revealed a visceral endoderm pattern of
      Indian hedgehog (Ihh) in wild-type E6.5 embryos. However, in both EXT1-deficient
      embryos and wild-type embryos treated with heparitinase I, Ihh failed to
      associate with the cells. The effect of the EXT1 deletion on heparan sulfate
      formation was tested by HPLC and cellular glycosyltransferase activity assays.
      Heparan sulfate synthesis was abolished in EXT1 -/- ES cells and decreased to
      less than 50% in +/- cell lines. These results indicate that EXT1 is essential
      for both gastrulation and heparan sulfate biosynthesis in early embryonic
      development.

PMID- 10926770
TI  - Oocyte development in Hydra involves selection from competent precursor cells.
AB  - We have investigated oocyte development in Hydra vulgaris, a member of one of the
      oldest metazoan phyla. We show that oocyte determination involves a mechanism
      that establishes a subset of precursor interstitial cells competent to
      differentiate into oocytes. The oocyte is singled out from this subset and the
      competence of the remaining cells to become oocytes dramatically decreases as
      they adopt the alternative nurse cell fate. Progression through the nurse cell
      differentiation program requires the presence of the oocyte. When the oocyte is
      removed from the egg field, nurse cells abort their differentiation program,
      undergo apoptosis, and are phagocytosed and degraded by somatic epithelial cells.
      However, in the presence of the oocyte, nurse cells differentiate and enter an
      unusual apoptosis program where they are phagocytosed by the oocyte, but are not
      degraded. We show that the oocyte is able to induce this unusual apoptosis
      program in immature nurse cells that have not completed differentiation. A new
      model for oocyte development in Hydra is discussed.

PMID- 10926769
TI  - Role of hyaluronan and CD44 in in vitro branching morphogenesis of ureteric bud
      cells.
AB  - Mutual interaction between the metanephric mesenchyme (MM) and the ureteric bud
      (UB) in the developing kidney leads to branching morphogenesis and the formation
      of the ureteric tree. A UB-derived cell line, stimulated by conditioned medium
      derived from an embryonic MM cell line (or, similarly, by 10% fetal calf serum),
      forms branching tubules under three-dimensional culture conditions (H. Sakurai et
      al., 1997, Proc. Natl. Acad. Sci. USA 94, 6279-6284). The formation of branching
      tubules in this simple in vitro system for early nephrogenesis is highly
      sensitive to the matrix environment, a key component of which is the
      glycosaminoglycan hyaluronan (HA). Consistent with this, we found that HA in the
      extracellular environment markedly stimulated the formation of cellular processes
      and multicellular cords (early steps in branching morphogenesis) and also acted
      as a cell survival factor. Inhibition of HA binding to the cells by addition of
      blocking antibodies to CD44, the principal cell surface receptor for HA, or
      degradation of HA by the addition of Streptomyces hyaluronidase resulted in
      decreased cell survival and diminished morphogenesis, indicating that the HA-CD44
      axis plays a central role in in vitro branching morphogenesis. Analysis of the
      expression of a large number of genes displayed on a cDNA array revealed that
      significant changes in gene expression in cells undergoing morphogenesis in the
      presence of HA were limited to a small subset of genes regulating apoptosis,
      proliferation, and morphogenesis. This included upregulation by HA of its
      receptor, CD44, which was found to largely localize to the tips of branching
      cellular processes. In the embryonic kidney, HA was found near the developing
      ureteric tree and CD44 was expressed basolaterally in UB-derived structures. In
      addition, both UB and MM appear to express HA synthase, suggesting their ability
      to secrete HA. We propose that HA promotes branching morphogenesis by creating a
      positive feedback loop that results in (1) enhanced interaction of HA-CD44 at
      branching tips (possibly leading to localization of HA binding morphoregulatory
      factors at the tips) and (2) an activated transcriptional program favoring cell
      survival/proliferation and migration/morphogenesis of cells through matrix by the
      expression of key morphoregulatory molecules. Furthermore, since HA,
      hyaluronidase, and CD44 have been functionally implicated in branching
      morphogenesis in this model, and since HA, CD44, and HA synthase are all
      expressed in an appropriate spatiotemporal fashion in the developing kidney, we
      propose that these molecules may, together, constitute a morphoregulatory pathway
      that plays a key role in sequential cycles of branching morphogenesis in the UB.

PMID- 10926771
TI  - Leech segmental repeats develop normally in the absence of signals from either
      anterior or posterior segments.
AB  - We have investigated whether the development of segmental repeats is autonomous
      in the embryo of the leech Helobdella robusta. The segmental tissues of the
      germinal band arise from progeny of five stem cells called teloblasts. Asymmetric
      divisions of the teloblasts form chains of segment founder cells (called primary
      blast cells) that divide in a stereotypical manner to produce differentiated
      descendants. Using two distinct techniques, we have looked for potential
      interactions between neighboring blast cell clones along the anterior-posterior
      axis. In one technique, we prevented the birth of primary blast cells by
      injection of DNase I into the teloblast, thereby depriving the last blast cell
      produced before the ablation of its normal posterior neighbors. We also ablated
      single blast cells with a laser microbeam, which allowed us to assess potential
      signals acting on either more anterior or more posterior primary blast cell
      clones. Our results suggest that interactions along the anterior-posterior axis
      between neighboring primary blast cell clones are not required for development of
      normal segmental organization within the blast cell clone. We also examined the
      possibility that blast cells receive redundant signals from both anterior and
      posterior neighboring clones and that either is sufficient for normal
      development. Using double blast cell laser ablations to isolate a primary blast
      cell clone by removal of both its anterior and its posterior neighbor, we found
      that the isolated clone still develops normally. These results reveal that the
      fundamental segmental repeat in the leech embryo, the primary blast cell clone,
      can develop normally in the apparent absence of signals from adjacent repeats
      along the anterior-posterior axis.

PMID- 10926772
TI  - A molecular basis for estrogen-induced cryptorchidism.
AB  - Male sexual differentiation relies upon testicular secretion of the hormones
      testosterone, Mullerian inhibiting substance, and insulin-3 (Insl3). Insl3 is
      responsible for testicular descent through virilization and outgrowth of the
      embryonic gubernaculum. In mouse, prenatal exposure to 17beta-estradiol and the
      nonsteroidal synthetic estrogen diethylstilbestrol (DES) disturbs the endocrine
      balance, causing demasculinizing and feminizing effects in the male embryo,
      including impaired testicular descent (cryptorchidism). In the current study, we
      show that maternal exposure to estrogens, including 17alpha- and beta-estradiol,
      as well as DES, specifically down regulates Insl3 expression in embryonic Leydig
      cells, thereby providing a mechanism for cryptorchidism. These experiments may
      have implications for the widespread use of estrogenic substances in agriculture
      and the environment.

PMID- 10926773
TI  - Convergence of dorsal, dpp, and egfr signaling pathways subdivides the drosophila
      neuroectoderm into three dorsal-ventral columns.
AB  - An important question in neurobiology is how different cell fates are established
      along the dorsoventral (DV) axis of the central nervous system (CNS). Here we
      investigate the origins of DV patterning within the Drosophila CNS. The earliest
      sign of neural DV patterning is the expression of three homeobox genes in the
      neuroectoderm-ventral nervous system defective (vnd), intermediate neuroblasts
      defective (ind), and muscle segment homeobox (msh)-which are expressed in
      ventral, intermediate, and dorsal columns of neuroectoderm, respectively.
      Previous studies have shown that the Dorsal, Decapentaplegic (Dpp), and EGF
      receptor (Egfr) signaling pathways regulate embryonic DV patterning, as well as
      aspects of CNS patterning. Here we describe the earliest expression of each DV
      column gene (vnd, ind, and msh), the regulatory relationships between all three
      DV column genes, and the role of the Dorsal, Dpp, and Egfr signaling pathways in
      defining vnd, ind, and msh expression domains. We confirm that the vnd domain is
      established by Dorsal and maintained by Egfr, but unlike a previous report we
      show that vnd is not regulated by Dpp signaling. We show that ind expression
      requires both Dorsal and Egfr signaling for activation and positioning of its
      dorsal border, and that abnormally high Dpp can repress ind expression. Finally,
      we show that the msh domain is defined by repression: it occurs only where Dpp,
      Vnd, and Ind activity is low. We conclude that the initial diversification of
      cell fates along the DV axis of the CNS is coordinately established by Dorsal,
      Dpp, and Egfr signaling pathways. Understanding the mechanisms involved in
      patterning vnd, ind, and msh expression is important, because DV columnar
      homeobox gene expression in the neuroectoderm is an early, essential, and
      evolutionarily conserved step in generating neuronal diversity along the DV axis
      of the CNS.

PMID- 10926774
TI  - Characterization of Hoxa-10/Hoxa-11 transheterozygotes reveals functional
      redundancy and regulatory interactions.
AB  - Hox genes show related sequences and overlapping expression domains that often
      reflect functional redundancy as well as a common evolutionary origin. To
      accurately define their functions, it has become necessary to compare phenotypes
      of mice with single and multiple Hox gene mutations. Here, we focus on two Abd-B
      type genes, Hoxa-10 and Hoxa-11, which are coexpressed in developing vertebrae,
      limbs, and reproductive tracts. To assess possible functional redundancy between
      these two genes, Hoxa-10/Hoxa-11 transheterozygotes were produced by genetic
      intercrosses and analyzed. This compound mutation resulted in synergistic defects
      in transheterozygous limbs and reproductive tracts, but not in vertebrae. In the
      forelimb, distal radial/ulnar thickening and pisiform/triangular carpal fusion
      were observed in 35 and 21% of transheterozygotes, respectively, but were
      effectively absent in Hoxa-10 and Hoxa-11 +/- forelimbs. In the hindlimb, distal
      tibial/fibular thickening and loss of tibial/fibular fusion were observed in >80%
      of transheterozygotes but in no Hoxa-10 or Hoxa-11 +/- hindlimbs, and all
      transheterozygotes displayed reduced medial patellar sesamoids, compared to
      modest incidences in Hoxa-10 and Hoxa-11 +/- mutants. Furthermore, while the
      reproductive tracts of Hoxa-10 and Hoxa-11 single heterozygous mutants of both
      sexes were primarily unaffected, male transheterozygotes displayed cryptorchidism
      and abnormal tortuosity of the ductus deferens, and female transheterozygotes
      exhibited abnormal uterotubal junctions and narrowing of the uterus. In addition
      we observed that the targeted mutations of Hoxa-10 and Hoxa-11 each affected the
      expression of the other gene in the developing prevertebra and reproductive
      tracts. These results provide a measure of the functional redundancy of Hoxa-10
      and Hoxa-11 and a deeper understanding of the phenotypes resulting in the single
      mutants and help elucidate the regulatory interactions between these two genes.

PMID- 10926775
TI  - A role for cyclin A1 in the activation of MPF and G2-M transition during meiosis
      of male germ cells in mice.
AB  - Cell-cycle transition at G2-M is controlled by MPF (M-phase-promoting factor), a
      complex consisting of the Cdc2 kinase and a B-type cyclin. We have shown that in
      mice, targeted disruption of an A-type cyclin gene, cyclin A1, results in a block
      of spermatogenesis prior to the entry into metaphase I. The meiotic arrest is
      accompanied by a defect in Cdc2 kinase activation at the G2--M transition,
      raising the possibility that a cyclin A1-dependent process dictates the
      activation of MPF. Here we show that like Cdc2, the expression of B-type cyclins
      is retained in cyclin A1-deficient spermatocytes, while their associated kinases
      are kept at inactive states. Treatment of arrested germ cells with the protein
      phosphatase type-1 and -2A inhibitor okadaic acid restores the MPF activity and
      induces entry into M phase and the formation of normally condensed chromosome
      bivalents, concomitant with hyperphosphorylation of Cdc25 proteins. Conversely,
      inhibition of tyrosine phosphatases, including Cdc25s, by vanadate suppresses the
      okadaic acid-induced metaphase induction. The highest levels of Cdc25A and Cdc25C
      expression and their subcellular localization during meiotic prophase coincide
      with that of cyclin A1, and when overexpressed in HeLa cells, cyclin A1
      coimmunoprecipitates with Cdc25A. Furthermore, the protein kinase complexes
      consisting of cyclin A1 and either Cdc2 or Cdk2 phosphorylate both Cdc25A and
      Cdc25C in vitro. These results suggest that in normal meiotic male germ cells,
      cyclin A1 participates in the regulation of other protein kinases or phosphatases
      critical for the G2-M transition. In particular, it may be directly involved in
      the initial amplification of MPF through the activating phosphorylation on Cdc25
      phosphatases.

PMID- 10926776
TI  - The Drosophila PAR domain protein 1 (Pdp1) gene encodes multiple differentially
      expressed mRNAs and proteins through the use of multiple enhancers and promoters.
AB  - Transcription factors are often expressed at several times and in multiple
      tissues during development and regulate diverse sets of downstream target genes
      by varying their combinatorial interactions with other transcription factors. The
      Drosophila Tropomyosin I (TmI) gene is regulated by a complex of proteins within
      the enhancer that synergistically interacts with MEF2 to activate TmI
      transcription as muscle cells fuse and differentiate. One of the components of
      this complex is PDP1 (PAR domain protein 1), a basic leucine zipper transcription
      factor that is highly homologous to three vertebrate genes that are members of
      the PAR domain subfamily. We have isolated and describe here the structure of the
      Pdp1 gene. The Pdp1 gene is complex, containing at least four transcriptional
      start sites and producing at least six different mRNAs and PDP1 isoforms. Five of
      the PDP1 isoforms differ by the substitution or insertion of amino acids at or
      near the N-terminal of the protein. At least three of these alternately spliced
      transcripts are differentially expressed in different tissues of the developing
      embryo in which PDP1 expression is correlated with the differentiation of
      different cell types. A sixth isoform is produced by splicing out part of the PAR
      and basic DNA binding domains, and DNA binding and transient transfection
      experiments suggest that it functions as a dominant negative inhibitor of
      transcription. Furthermore, two enhancers have been identified within the gene
      that express in the somatic mesodermal precursors to body wall muscles and fat
      body and together direct expression in other tissues that closely mimics that of
      the endogenous gene. These results show that Pdp1 is widely expressed, including
      in muscle, fat, and gut precursors, and is likely involved in the transcriptional
      control of different developmental pathways through the use of differentially
      expressed PDP1 isoforms. Furthermore, the similarities between Pdp1 and the other
      PAR domain genes suggest that Pdp1 is the homologue of the vertebrate genes.

PMID- 10926777
TI  - Neurotrophin-3 promotes the survival of a limited subpopulation of cutaneous
      sensory neurons.
AB  - In the chick embryo, exogenous neurotrophin-3 (NT3) is sufficient to promote the
      differentiation of proprioceptive afferents even in the absence of limb muscle
      targets. To determine if NT3 can promote the differentiation of this phenotype in
      afferents with cutaneous targets, we analyzed the effects of chronic NT3 on
      cutaneous and muscle sensory neurons that express trkC, a receptor for NT3. In
      normal embryos, retrograde labeling and immunohistochemistry showed that about
      75% of large-diameter muscle afferents express trkC, whereas only about 7% of
      large-diameter cutaneous afferents express this protein. After chronic treatment
      with NT3 during the cell death period, both populations of trkC(+) neurons were
      increased approximately twofold. Because this treatment is known to block cell
      death in sensory neurons, these results indicate that NT3 can promote the
      survival of both proprioceptive afferents and cutaneous afferents. To examine the
      phenotype of the cutaneous afferents rescued by NT3, we analyzed their
      projections and connections using transganglionic labeling and
      electrophysiological recording. The results indicate that exogenous NT3 neither
      altered the pattern of spinal projections nor caused cutaneous afferents to form
      monosynaptic connections with motor neurons. These results demonstrate that
      selective cell death does not contribute to the modality-specific pattern of
      spinal innervation and suggest that proprioceptive afferents may innervate muscle
      selectively.

PMID- 10926778
TI  - Development and control of tissue separation at gastrulation in Xenopus.
AB  - During Xenopus gastrulation, the internalizing mesendodermal cell mass is brought
      into contact with the multilayered blastocoel roof. The two tissues do not fuse,
      but remain separated by the cleft of Brachet. This maintenance of a stable
      interface is a precondition for the movement of the two tissues past each other.
      We show that separation behavior, i.e., the property of internalized cells to
      remain on the surface of the blastocoel roof substratum, spreads before and
      during gastrulation from the vegetal endoderm into the anterior and eventually
      the posterior mesoderm, roughly in parallel to internalization movement.
      Correspondingly, the blastocoel roof develops differential repulsion behavior,
      i.e., the ability to specifically repell cells showing separation behavior. From
      the effects of overexpressing wild-type or dominant negative XB/U or EP/C
      cadherins we conclude that separation behavior may require modulation of cadherin
      function. Further, we show that the paired-class homeodomain transcription
      factors Mix.1 and gsc are involved in the control of separation behavior in the
      anterior mesoderm. We present evidence that in this function, Mix.1 and gsc may
      cooperate to repress transcription.

PMID- 10926779
TI  - Cyclopamine inhibition of Sonic hedgehog signal transduction is not mediated
      through effects on cholesterol transport.
AB  - Cyclopamine is a teratogenic steroidal alkaloid that causes cyclopia by blocking
      Sonic hedgehog (Shh) signal transduction. We have tested whether this activity of
      cyclopamine is related to disruption of cellular cholesterol transport and
      putative secondary effects on the Shh receptor, Patched (Ptc). First, we report
      that the potent antagonism of Shh signaling by cyclopamine is not a general
      property of steroidal alkaloids with similar structure. The structural features
      of steroidal alkaloids previously associated with the induction of
      holoprosencephaly in whole animals are also associated with inhibition of Shh
      signaling in vitro. Second, by comparing the effects of cyclopamine on Shh
      signaling with those of compounds known to block cholesterol transport, we show
      that the action of cyclopamine cannot be explained by inhibition of intracellular
      cholesterol transport. However, compounds that block cholesterol transport by
      affecting the vesicular trafficking of the Niemann-Pick C1 protein (NPC1), which
      is structurally similar to Ptc, are weak Shh antagonists. Rather than supporting
      a direct link between cholesterol homeostasis and Shh signaling, our findings
      suggest that the functions of both NPC1 and Ptc involve a common vesicular
      transport pathway. Consistent with this model, we find that Ptc and NPC1
      colocalize extensively in a vesicular compartment in cotransfected cells.

PMID- 10926780
TI  - Tyrosine kinase-dependent activation of phospholipase Cgamma is required for
      calcium transient in Xenopus egg fertilization.
AB  - In a previous study (K.-I. Sato et al., 1999, Dev. Biol. 209, 308-320), we
      presented evidence that a Src-related protein-tyrosine kinase (PTK), named Xyk,
      may act upstream of the calcium release in fertilization of the Xenopus egg. In
      the present study, we examined whether PTK activation of phospholipase Cgamma
      (PLCgamma) plays a role in the fertilization-induced calcium signaling.
      Immunoprecipitation studies show that Xenopus egg PLCgamma is tyrosine
      phosphorylated and activated within a few minutes after fertilization but not
      after A23187-induced egg activation. Consistently, we observed a fertilization
      induced association of PLCgamma with Xyk activity that was not seen in A23187
      activated eggs. A Src-specific PTK inhibitor, PP1, blocked effectively the
      fertilization-induced association of PLCgamma with Xyk activity and up-regulation
      of PLCgamma, when microinjected into the egg. In addition, a PLC inhibitor, U
      73122, inhibited sperm-induced inositol 1,4,5-trisphosphate production and the
      calcium transient and subsequent calcium-dependent events such as cortical
      contraction, elevation of fertilization envelope, and tyrosine dephosphorylation
      of p42 MAP kinase, all of which were also inhibited by PP1. On the other hand,
      A23187 could cause the calcium response and calcium-dependent events in eggs
      injected with PP1 or U-73122. These results support the idea that Xenopus egg
      fertilization requires Src-family PTK-dependent PLCgamma activity that acts
      upstream of the calcium-dependent signaling pathway.

PMID- 10926782
TI  - The isolation of two juvenile hormone-inducible genes in Drosophila melanogaster.
AB  - Juvenile hormone (JH) is an important regulator of both insect development and
      reproductive maturation. Although the molecular mechanism of JH action is not yet
      known, there is growing circumstantial evidence that JH directly regulates gene
      expression. In the absence of a JH target gene, however, this suggestion has
      remained speculative. Cultured Drosophila S2 cells have been used to identify
      genes whose expression is regulated by JH. Employing differential display we
      identified several genes whose transcripts accumulate in cells treated with the
      JH agonist methoprene. Two of the genes-JhI-1 and JhI-26-were cloned and
      characterized in detail. For both genes, transcripts showed rapid and specific
      induction in the presence of either methoprene or JHIII, but not in the presence
      of other biologically inactive compounds of similar chemical structure.
      Accumulation of JhI-1 and JhI-26 RNAs requires continuous hormone presence. The
      developmental expression of the two JH-inducible genes corresponds to the
      abundance profile of JH in vivo. Furthermore, topical methoprene application to
      pupae leads to the ectopic accumulation of JhI-1 and JhI-26 transcripts.

PMID- 10926781
TI  - Xlim-1 and LIM domain binding protein 1 cooperate with various transcription
      factors in the regulation of the goosecoid promoter.
AB  - The homeobox genes Xlim-1 and goosecoid (gsc) are coexpressed in the Spemann
      organizer and later in the prechordal plate that acts as head organizer. Based on
      our previous finding that gsc is a possible target gene for Xlim-1, we studied
      the regulation of gsc transcription by Xlim-1 and other regulatory genes
      expressed at gastrula stages, by using gsc-luciferase reporter constructs
      injected into animal explants. A 492-bp upstream region of the gsc promoter
      responds to Xlim-1/3m, an activated form of Xlim-1, and to a combination of wild
      type Xlim-1 and Ldb1, a LIM domain binding protein, supporting the view that gsc
      is a direct target of Xlim-1. Footprint and electrophoretic mobility shift assays
      with GST-homeodomain fusion proteins and embryo extracts overexpressing FLAG
      tagged full-length proteins showed that the Xlim-1 homeodomain or Xlim-1/Ldb1
      complex recognize several TAATXY core elements in the 492-bp upstream region,
      where XY is TA, TG, CA, or GG. Some of these elements are also bound by the
      ventral factor PV.1, whereas a TAATCT element did not bind Xlim-1 or PV.1 but did
      bind the anterior factors Otx2 and Gsc. These proteins modulate the activity of
      the gsc reporter in animal caps: Otx2 activates the reporter synergistically with
      Xlim-1 plus Ldb1, whereas Gsc and PV.1 strongly repress reporter activity. We
      show further, using animal cap assays, that the endogenous gsc gene was
      synergistically activated by Xlim-1, Ldb1, and Otx2 and that the endogenous otx2
      gene was activated by Xlim-1/3m, and this activation was suppressed by the
      posterior factor Xbra. Based on these data, we propose a model for gene
      interactions in the specification of dorsoventral and anteroposterior differences
      in the mesoderm during gastrulation.

PMID- 10926783
TI  - sem-4 promotes vulval cell-fate determination in Caenorhabditis elegans through
      regulation of lin-39 Hox.
AB  - Vulval cell-fate determination in Caenorhabditis elegans requires the action of
      numerous gene products, including components of the Ras/Raf/MAPK signaling
      cascade and the hox gene lin-39. sem-4 encodes a zinc finger protein with
      previously characterized roles in fate specification of sex myoblasts,
      coelomocytes, and multiple neuronal lineages in C. elegans (M. Basson and R.
      Horvitz, 1996, Genes Dev. 10, 1953-1965). By characterizing three new alleles of
      sem-4 that we identified in a screen for vulval-defective mutants, we determined
      that loss of sem-4 activity results in abnormal specification of the secondary
      vulval cell lineages. We analyzed sem-4 interactions with other genes involved in
      vulval differentiation and determined that sem-4 does not function directly in
      the Ras-mediated signal transduction pathway but acts in close association with
      and upstream of lin-39 to promote vulval cell fate. We demonstrate that sem-4
      regulates lin-39 expression and propose that sem-4 is a regulator of lin-39 in
      the vulval cell-fate determination pathway that may act to link lin-39 to
      incoming signals.

PMID- 10926784
TI  - Is there a role for surgical cytoreduction in stage IV endometrial cancer?

PMID- 10926785
TI  - Stage IVB endometrial carcinoma: the role of cytoreductive surgery and
      determinants of survival.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of cytoreductive
      surgery and survival determinants in patients with Stage IVB endometrial
      carcinoma. METHODS: All patients with Stage IVB endometrial carcinoma diagnosed
      between 1/1/90 and 12/31/98 were identified from tumor registry databases.
      Individual patient data were collected retrospectively. Survival analyses and
      comparisons were performed using the Kaplan-Meier method and the log-rank test.
      The Cox proportional hazards model was used to identify independent variables
      associated with survival. RESULTS: Sixty-five patients underwent surgery as
      primary therapy for Stage IVB endometrial carcinoma (median survival 14.8
      months). The median age of the population was 65 years (range 29-85 years); 89.2%
      of patients were postmenopausal, and 21.5% were nulliparous. The most common
      histologic subtypes were endometrioid (33.8%), serous (32.3%), and mixed (16.9%).
      Optimal cytoreductive surgery (residual tumor < or =1 cm in maximal diameter) was
      accomplished in 36 patients (55.4%), while 29 patients (44.6%) were left with >1
      cm residual disease. The median survival rate of patients undergoing optimal
      surgery was 34.3 months, a statistically significant advantage compared to
      patients with >1 cm residual tumor (11.0 months, P = 0.0001). Among those with
      optimal surgery, patients with only microscopic residual disease survived
      significantly longer than patients with optimal but macroscopic residual tumor.
      Higher performance status, age < or = 58 years, and adjuvant chemotherapy
      followed by radiation therapy were also significantly associated with superior
      survival on univariate analysis. On multivariate analysis, residual disease (P =
      0.0001), performance status (P = 0.043), and age (P = 0.023) were independent
      predictors of survival. CONCLUSIONS: The amount of residual disease after
      cytoreductive surgery, age, and performance status appear to be important
      determinants of survival in patients with Stage IVB endometrial carcinoma.
      Maximal cytoreduction should be the goal at the time of primary surgery for
      advanced disease. For selected patients, combined postoperative chemotherapy and
      radiation therapy may provide some therapeutic benefit.

PMID- 10926787
TI  - The rising incidence of adenocarcinoma relative to squamous cell carcinoma of the
      uterine cervix in the United States--a 24-year population-based study.
AB  - OBJECTIVE: The aim of this study was to compare the age-adjusted incidence and
      survival for invasive adenocarcinoma and squamous cell carcinoma of the uterine
      cervix using population-based data. METHODS: The SEER database was used to
      identify all cases of cervical cancer registered between 1973 and 1996. Stage was
      defined as localized, regional, or distant. Age-adjusted incidence rates were
      analyzed statistically using the Jonchkeere-Terpstra exact test for trends.
      Relative and observed survival rates, respectively, were compared using z tests
      and log-rank tests. RESULTS: The age-adjusted incidence rates per 100,000 for all
      invasive cervical cancers decreased by 36.9% over 24 years [12.35 (1973-1977) vs
      7.79 (1993-1996)]. Similarly, the age-adjusted incidence rates for squamous cell
      carcinoma declined by 41.9% [9.45 (1973-1977) vs 5.49 (1993-1996)]. In contrast,
      the age-adjusted incidence rates for adenocarcinoma increased by 29.1% [1.34
      (1973-1977) vs 1.73 (1993-1996)]. The proportion of adenocarcinoma increased
      107.4% relative to all cervical cancer, 95.2% relative to squamous cell
      carcinoma, and 49.3% relative to the population of women at risk [10. 8% vs 22.4%
      (P < 0.001), 12.4% vs 24.0% (P < 0.001), and 1.40 vs 2. 09 per 100,000 women (P <
      0.001), respectively]. Observed survival rates for adenocarcinoma vs squamous
      cell carcinoma were poorer for regional (P = 0.04), but not localized or distant
      disease. CONCLUSIONS: Over the past 24 years, the incidence of all cervical
      cancer and squamous cell carcinoma has continued to decline. However, the
      proportion of adenocarcinoma relative to squamous cell carcinoma and to all
      cervical cancers has doubled, and the rate of adenocarcinoma per population at
      risk has also increased. These results suggest that current screening practices
      in the United States are insufficient to detect a significant proportion of
      adenocarcinoma precursor lesions.

PMID- 10926786
TI  - Guidelines for the stratification of patients recruited to trials of therapy for
      low-risk gestational trophoblastic tumor.
AB  - OBJECTIVE: The aim of the study was to initiate a search for factors which might
      independently predict the need for salvage therapy in patients with low-risk
      gestational trophoblastic tumor. METHODS: The independent effect of six factors
      on the need for salvage chemotherapy was assessed in patients with low-risk
      gestational trophoblastic tumor who were treated with low-dose methotrexate and
      folinic acid. The accuracies of World Health Organization and Charing Cross
      Hospital scores were also compared. RESULTS: Age, pretreatment beta hCG,
      antecedent pregnancy-treatment interval, and the presence of chest metastases
      detected on chest X ray were not significantly predictive. The size of tumor (P =
      0.001) and the presence of chest metastases on chest computerized tomography (P =
      0. 00028) had independent, statistically significant predictive power, and a
      simple prognostic index was derived from these variables. The World Health
      Organization score was found to be significantly better than the Charing Cross
      Hospital score. The accuracy of the simple prognostic index was slightly greater
      than that of the World Health Organization score, although this was not
      statistically significant. CONCLUSIONS: These results confirm that patients
      entered into studies of different therapies for low-risk gestational
      trophoblastic tumor should be stratified and that a simple score, derived from
      the results of tumor size and chest computerized tomography, is potentially as
      good as the World Health Organization score for predicting the need for salvage
      therapy.

PMID- 10926788
TI  - Expression of matrix metalloproteinases and related tissue inhibitors in the cyst
      fluids of ovarian mucinous neoplasms.
AB  - OBJECTIVES AND METHODS: The growth of an ovarian cystic neoplasm often involves
      its invasion into and destruction of the extracellular matrix. We examined
      neoplastic cysts of ovarian mucinous tumors for the presence of matrix
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) using zymography
      (in situ zymography, gelatin zymography, and casein zymography) and enzyme-linked
      immunosorbent assay. RESULTS: Matriolytic activity was detected within the cystic
      contents and cytoplasm of the lining epithelial cells of the cyst by in situ
      zymography. This intracystic matriolytic activity was thought to originate mainly
      in the epithelial cells. The activated form of MMP-9 was seen in all carcinoma
      and borderline fluids and in 7 of 15 adenomas. The concentration of MMP-9 was
      higher in carcinoma fluids than in borderline and adenoma fluids (P < 0.05). TIMP
      1, which specifically binds to MMP-9, was also higher in carcinoma and borderline
      fluids than in adenoma fluids (P < 0.05). MMP-2 activity was nearly ubiquitously
      present in all cyst fluids, irrespective of the fluid's histologic category. The
      amount of MMP-2 was highest in the carcinoma category, although not to a
      statistically significant degree. TIMP-2, a specific inhibitor for MMP-2, was
      significantly lower in the borderline category than in the adenoma category. The
      molar ratios of TIMP-1/MMP-9 (not significant) and TIMP-2/MMP-2 (P < 0.05) were
      higher in the adenoma category. Expressions of trypsin, MMP-7, and MMP-9 were
      generally higher in carcinoma and borderline fluids than in adenoma fluids.
      CONCLUSIONS: These observations indicate the importance of ovarian cystic fluids
      for analyzing tumor-associated matriolytic activities. The findings suggest that
      these matriolytic enzymes, together with the presence of their inhibitors, play
      an important role in the growth of ovarian mucinous tumors.

PMID- 10926789
TI  - Endocervical cancer is associated with an increase in the ligands and receptors
      for transforming growth factor-beta and a contrasting decrease in p27(Kip1).
AB  - OBJECTIVE: The aim of this study was to investigate the relationship between the
      expression of the TGF-beta ligands and TGF-beta receptors to the expression of
      p27(Kip1), a TGF-beta-regulated gene, in endocervical cancer. METHODS: To examine
      the expression of TGF-beta and p27(Kip1) in malignant transformation of the
      uterine endocervix, a panel of 23 formalin-fixed and paraffin-embedded human
      cervical specimens, including 8 with benign endocervical glands, 8 with cervical
      adenocarcinoma in situ, and 7 with cervical adenocarcinomas, was used. Tissues
      were immunostained with polyclonal antibodies that react specifically with TGF
      beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF-beta RII, and p27(Kip1).
      RESULTS: Immunostaining for TGF-beta 1, TGF-beta 2, TGF-beta 3, TGF-beta RI, TGF
      beta RII, and p27(Kip1) was detected in normal endocervix, with the TGF-betas
      showing weak cytoplasmic staining, while p27(Kip1) showed strong nuclear
      staining. Expression of TGF-beta increased significantly upon neoplastic
      transformation with the TGF-beta ligands and receptors showing strong cytoplasmic
      staining in adenocarcinoma in situ compared to normal endocervix. Interestingly,
      expression of TGF-beta was lower in adenocarcinoma than in adenocarcinoma in
      situ, but still significantly higher than in normal endocervix. TGF-beta 2 and
      TGF-beta 3 showed higher levels of immunostaining than TGF-beta 1 in
      adenocarcinomas. In contrast, p27(Kip1) protein expression decreased with
      progressive malignancy, with lower p27(Kip1) protein levels detected in
      adenocarcinoma than in adenocarcinoma in situ, while normal endocervix showed the
      highest level of p27(Kip1) protein expression. CONCLUSION: Elevated expression of
      the TGF-beta ligands and receptors is found in both cervical adenocarcinoma in
      situ and adenocarcinoma compared to normal endocervix. In contrast, a progressive
      decrease in p27(Kip1) occurs upon neoplastic transformation of the normal
      endocervix to cervical adenocarcinoma. These results suggest that neoplastic
      transformation of the endocervix may be related to dysregulation of TGF-beta and
      p27(Kip1) seen as an elevation of TGF-beta and a reduction of p27(Kip1)
      expression that may lead to loss of cell cycle control.

PMID- 10926790
TI  - Placebo-controlled trial of indole-3-carbinol in the treatment of CIN.
AB  - OBJECTIVE: Most precancerous lesions of the cervix are treated with surgery or
      ablative therapy. Chemoprevention, using natural and synthetic compounds, may
      intervene in the early precancerous stages of carcinogenesis and prevent the
      development of invasive disease. Our trial used indole-3-carbinol (I-3-C)
      administered orally to treat women with CIN as a therapeutic for cervical CIN.
      METHODS: Thirty patients with biopsy proven CIN II-III were randomized to receive
      placebo or 200, or 400 mg/day I-3-C administered orally for 12 weeks. If
      persistent CIN was diagnosed by cervical biopsy at the end of the trial, loop
      electrocautery excision procedure of the transformation zone was performed. HPV
      status was assessed in all patients. RESULTS: None (0 of 10) of the patients in
      the placebo group had complete regression of CIN. In contrast 4 of 8 patients in
      the 200 mg/day arm and 4 of 9 patients in the 400 mg/day arm had complete
      regression based on their 12-week biopsy. This protective effect of I-3-C is
      shown by a relative risk (RR) of 0.50 ((95% CI, 0. 25 to 0.99) P = 0.023) for the
      200 mg/day group and a RR of 0.55 ((95% CI, 0.31 to 0.99) P = 0.032) for the 400
      mg/day group. HPV was detected in 7 of 10 placebo patients, in 7 of 8 in the 200
      mg/day group, and in 8 of 9 in the 400 mg/day group. CONCLUSIONS: There was a
      statistically significant regression of CIN in patients treated with I-3-C orally
      compared with placebo. The 2/16 alpha-hydroxyestrone ratio changed in a dose
      dependent fashion.

PMID- 10926791
TI  - Biomarker conservation in primary and metastatic epithelial ovarian cancer.
AB  - PURPOSE: The aim of this study was to compare the overexpression of specific
      biomarkers in primary advanced and recurrent epithelial ovarian cancers. METHODS:
      Biomarker expression by epithelial ovarian cancer specimens from primary and
      metastatic sites was examined by immunohistochemistry and flow cytometry.
      Biomarker expression by subpopulations of tissues consisting of matched pairs of
      synchronous and metachronous lesions was also studied. RESULTS: A total of 3173
      epithelial ovarian cancer specimens were retrieved from women with FIGO Stage
      III/IV disease. These included lesions from 1036 primary and 2137 metastatic
      sites. The percentages of biomarker expression for primary and metastatic
      lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%;
      EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately
      73% of both primary and metastatic specimens were aneuploid, and approximately
      57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were
      found to be significantly different between the primary and metastatic tumors (P
      < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid
      primary lesions were associated with aneuploid metastases. Similarly, the
      distributions for MDR1, HER2, and p53 expression did not vary significantly
      between primary and metastatic sites. Pairings of metachronous cases (n = 66)
      revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their
      aneuploid status at the time of relapse. Furthermore, there were no significant
      changes in MDR1, p53, or HER2 expression at relapse. CONCLUSIONS: With the
      exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in
      this study probably does not play a significant role in imparting clinical
      heterogeneity during the advanced and recurrent stages of epithelial ovarian
      cancer. These particular genes likely undergo alterations early in the
      tumorigenesis process before metastases have become established.

PMID- 10926792
TI  - The significance of thrombocytosis in patients with locally advanced cervical
      carcinoma: a Gynecologic Oncology Group study.
AB  - OBJECTIVE: The aim of this study was to determine the incidence of thrombocytosis
      and its possible impact on survival probability among women with locally advanced
      cervical carcinoma. METHODS: The database of 294 patients with Stages IIB-IVA
      cervical carcinoma without periaortic node metastasis who were treated with
      standardized radiation therapy and concurrent hydroxyurea or misonidazole was
      analyzed. Pretreatment platelet counts were available for 291 patients who are
      the subject of this study. RESULTS: Thrombocytosis (platelet count >400 x
      10(9)/liter) was present in 86 (29.6%) of the 291 patients. A multivariate Cox
      proportional hazards model showed that patients without extrapelvic disease and
      with thrombocytosis had a 55% greater chance of dying than those without
      thrombocytosis (relative risk = 1.55, 95% confidence interval 1.08-2.21).
      Patients with thrombocytosis had larger tumors and more frequently had bilateral
      parametrial involvement, tumor fixation to the sidewall, and positive pelvic
      lymph nodes than patients without thrombocytosis. Thrombocytosis was not found to
      be a prognostic factor in patients with positive pelvic nodes. However, in
      patients with negative pelvic nodes, the presence or absence of thrombocytosis
      was related to survival. CONCLUSION: Thrombocytosis is a frequent finding among
      patients with advanced cervical carcinoma and seems to be related to tumor
      burden. Among patients with locally advanced cervical carcinoma who had negative
      pelvic nodes, those with thrombocytosis had a poorer survival.

PMID- 10926793
TI  - Phase II study of liposomal doxorubicin in advanced gynecologic cancers.
AB  - OBJECTIVE: Pegylated liposomal doxorubicin (Doxil) may have enhanced therapeutic
      efficacy and reduced toxicity compared with the parent compound. This phase II
      study further evaluates the activity of Doxil in patients with ovarian cancer and
      explores activity in other gynecologic cancers. METHODS: Sixty-three patients
      were treated with Doxil 50 mg/m(2) infused over 1 h; 44 were evaluable. Forty
      eight had epithelial ovarian cancer and all received prior treatment with
      cisplatin and paclitaxel: 27 received two to six prior regimens, 44 were platinum
      resistant, 21 patients had measurable disease, and 27 had evaluable disease only.
      RESULTS: The overall survival of these patients was 10 months (range, 0.25-33);
      progression-free survival was 3 months (range, 0.25-18). The response rate among
      those with measurable disease was 19%, with a median duration of 4.5 months
      (range, 3-12). The response rate of 22 patients with elevated CA-125 was 59%;
      median duration was 3.5 months (range, 1-12). Also, 27% achieved prolonged
      stabilization of disease for a median of 7 months (range, 5-18). Overall,
      treatment was well tolerated in this heavily pretreated population. Grade 3 and 4
      toxic effects were: 5 grade 3 stomatitis, 3 grade 3 skin, 1 each grade 4
      neutropenia and thrombocytopenia, 5 admits for infection, and no neutropenic
      fever; nausea and vomiting were uncommon in 204 cycles to ovarian cancer
      patients. CONCLUSION: This study demonstrates the activity of Doxil in heavily
      pretreated patients with ovarian cancer and poor prognostic features and confirms
      the prolonged responses and favorable toxicity profile. Encouraging findings were
      also observed in the patients with nonovarian gynecologic cancers.

PMID- 10926795
TI  - Intratumoral genetic heterogeneity and progression of endometrioid type
      endometrial adenocarcinomas.
AB  - OBJECTIVES: Development of genetic heterogeneity is one mechanism whereby tumors
      may acquire increasing aggressiveness during neoplastic progression. In this
      study we relate development of intratumoral genetic heterogeneity to invasion and
      metastatic spread of sporadic endometrioid (type I) endometrial adenocarcinomas.
      METHODS: Microsatellite unstable adenocarcinomas underwent detailed
      microsatellite allelotype mapping with reconstruction of neoplastic lineages
      using maximum parsimony analysis. RESULTS: Within individual patients, tumor
      allelotypes sometimes varied between regions of histologically identical tumor,
      indicating that genotypic variation may reflect differences inapparent by
      histology. Comparison of noninvasive (surface/luminal) with invasive (myometrial
      invasion or metastasis) carcinoma showed highly related genotypes in 3/8 cases in
      which the invasive component can be recognized as evolved from the superficial
      tumor lineage by progressive clonal selection. In 3/8 cases superficial and
      invasive genotypes independently evolved different sets of altered
      microsatellites, indicating either divergence at an early stage in tumor
      evolution or independent selection events. A total of 2/8 cases had random
      patterns of marker distribution between sampled areas that were not informative
      in delineating systematic relationships between surface and invasive tumor.
      CONCLUSIONS: We conclude from these results that endometrial tumor progression
      may occur through physical extension of existing clones or through creation of
      new subclones with altered growth properties. The latter occurs in about half of
      cases, where myometrial invasion may select for particular clones that are poorly
      represented on the luminal surface.

PMID- 10926794
TI  - Founder BRCA 1 and 2 mutations among a consecutive series of Ashkenazi Jewish
      ovarian cancer patients.
AB  - OBJECTIVE: The purpose of this study was to describe the incidence of the three
      Ashkenazi Jewish founder genetic BRCA 1 and 2 mutations among an unselected,
      consecutive group of Ashkenazi Jewish ovarian cancer patients. MATERIALS AND
      METHODS: From 7/30/96 to 4/12/99, 92 Ashkenazi Jewish patients with
      histologically confirmed epithelial ovarian cancer had surgery. All of these
      patients had DNA extracted from 5-microm sections of their paraffin-embedded
      surgical specimen tissue blocks using the Qiagen QIAamp tissue extraction kit. A
      multiplex (triplex) polymerase chain reaction was performed to amplify fragments
      for the 185delAG, 5382insC, and 6174delT mutations. The products were hybridized
      with normal and mutant probes for each of the three mutations. All clinical data
      were collected retrospectively and statistical significance was evaluated using
      the chi(2) test or a two-tailed Fisher's exact test, depending on the sample
      size. RESULTS: There were 23 patients positive for one of the three founder BRCA
      mutations. Fourteen patients were positive for the 185delAG mutation, 2 patients
      were positive for the 5382insC mutation, and 7 patients were positive for the
      6174 delT mutation (61, 9, and 30%, respectively). This represented a 25%
      incidence (95% CI: 16-34%) of one of the three founder BRCA mutations among our
      92 Ashkenazi Jewish ovarian cancer patients. None of the patients was positive
      for more than one mutation. There was no statistically significant difference in
      parity, histology, grade, or stage between the BRCA founder mutation positive and
      negative patients. The difference between the percentage of mutation carriers
      among patients with one affected first-degree relative (13/22 or 59%) compared to
      those without at least one affected first-degree relative (10/70 or 14%) was
      highly significant (P = 0.001). CONCLUSIONS: Ashkenazi Jewish ovarian cancer
      patients represent a group with a high likelihood of being carriers of BRCA 1 and
      2 genetic mutations, regardless of family history. As a result, all ovarian
      cancer patients who are of Ashkenazi Jewish descent should be counseled regarding
      BRCA 1 and 2 genetic screening, as well as the potential implications of these
      results for the patient as well as her relatives in terms of prognosis,
      screening, chemoprevention, and consideration of prophylactic surgical
      procedures.

PMID- 10926796
TI  - Hepatocyte growth factor promotes in vitro scattering and morphogenesis of human
      cervical carcinoma cells.
AB  - OBJECTIVE: Hepatocyte growth factor (HGF) enhances cell dissociation and
      morphogenesis in many forms of carcinomas including some, but not all, cervical
      carcinomas. In this study, we examined the effects of HGF on two cervical cancer
      cell lines, derived from the same tumor, with different growth patterns in vivo
      and in vitro. METHODS: Two cell lines, derived from the same cervical carcinoma,
      express spinous (C-4I) and basal (C4-II) squamous cell differentiation,
      respectively. A cell scattering assay was used to determine whether HGF would
      stimulate cell dissociation and motility. The morphogenetic capacity of HGF was
      assessed in collagen gel cultures, expression of the HGF receptor c-Met by
      Western blot analysis, and cadherin expression by immunofluorescence microscopy.
      RESULTS: HGF-induced cell scattering was intense in C-4II, but limited in C-4I
      cultures. In collagen gels, C-4I cells formed large, spherical compact colonies
      with necrotic centers while C-4II cells formed small, irregular colonies with no
      necrosis. HGF induced proliferation and branching morphogenesis in both lines,
      but more prominently in C-4II cultures. There was no difference in c-Met or E-
      and P-cadherin expression between C-4I and C-4II cultures, but the lines differed
      in their signal transduction responses to HGF. The scatter response was mediated
      primarily by phosphatidylinositol 3-kinase in line C-4I, but by mitogen-activated
      protein kinase in line C-4II. HGF induced collagen gel contraction by C-4 cells,
      demonstrating for the first time that HGF has the capacity to induce this
      function. CONCLUSIONS: The HGF-induced cell dispersion, morphogenesis, and
      collagen gel contraction in two cervical carcinoma cell lines were greatly
      influenced by differences between the lines in differentiation-associated
      properties. These properties, which include variations in extracellular matrix,
      junctional proteins, and signal transduction, may also modulate HGF action in
      vivo and thus determine patterns of invasiveness and growth of cervical
      carcinomas.

PMID- 10926797
TI  - Comparative study of ovarian cancer histopathology by registry pathologists and
      referral pathologists: a study by the Gilda Radner Familial Ovarian Cancer
      Registry.
AB  - OBJECTIVE: The aim of this study was to evaluate whether there is a significant
      difference in the pathology diagnoses of women in the Gilda Radner Familial
      Ovarian Cancer Registry between the two expert Registry pathologists and the
      referral pathologist. Inaccuracies in verification that ovarian cancer did occur
      in family members could lead to unnecessary prophylactic surgery or genetic
      testing. METHODS: A retrospective review was performed of (1) site of malignancy;
      (2) histopathology of malignancy; (3) grade of malignancy; and (4) the presence
      or absence of malignancy between the Registry and referral pathologists. RESULTS:
      There was 95.3% complete agreement between the Registry and the referral
      pathologist on site of origin with a major difference in only 1.0% of the cases.
      In comparison of histopathology, there was a 61.7% complete agreement, and only
      1.0% were considered major differences. There was 68.8% complete agreement in
      grade of the malignancy, whereas 2.3% were considered major differences.
      CONCLUSION: When constructing a family pedigree, it is important to obtain
      pathology reports to confirm the index case diagnosis of the presence or absence
      of ovarian cancer. However, because of the small percentage of major differences
      in diagnosis between the two Registry pathologists and the multiple referral
      pathologists, we believe genetic counselors and treating physicians can rely, in
      most instances, on the original histopathology report of verification of ovarian
      cancer without review of the original histopathology slides when recommending
      surveillance, genetic testing, and/or prophylactic surgery.

PMID- 10926799
TI  - Complete cytoreduction: is epithelial ovarian cancer confined to the pelvis
      biologically different from bulky abdominal disease?
AB  - OBJECTIVES: The aim of this study was to determine whether site and size of tumor
      masses prior to complete surgical cytoreduction affect outcome survival. METHODS:
      A retrospective review was performed of 53 women with stage II and III epithelial
      ovarian cancer following complete surgical cytoreduction. RESULTS: Fifteen cases
      (28%) were classified as stage II and the remaining 38 cases (72%) as stage III.
      The overall median survival was 58 months with overall 2- and 5-year survivals of
      76 and 42%, respectively. On univariate analysis, women with well differentiated
      tumors did significantly better than those with moderately or poorly
      differentiated tumours (P = 0.0009). FIGO stage did not reach statistical
      significance (P = 0.066). On multivariate analysis, comparing patient's age,
      previous history of pelvic surgery, previous history of malignancy, performance
      of lymphadenectomy for visibly/palpably enlarged nodes, performance of bowel
      resection, presence of concomitant tumors, positive pelvic and/or para-aortic
      lymph nodes, histological type, histological grade, and FIGO stage, only
      histological grade remained an independent variable affecting outcome survival (P
      = 0.0004; FIGO stage, P = 0.22) (hazard ratio = 6.5: well versus poor
      differentiation, 95% confidence interval, 1.7-25.5). CONCLUSION: When surgical
      cytoreduction to no visible disease has been achieved in women with stage II and
      III epithelial ovarian cancer, FIGO stage, i.e., site and size of tumor masses
      prior to surgical cytoreduction, does not appear to influence outcome survival.
      The aggressiveness of the remaining microscopic disease would seem to be
      determined largely by histological grade. Bearing in mind the retrospective
      nature of this study and the relatively small cohort of patients, the results
      would appear to suggest that it is unlikely that there are any other significant
      parameters (hidden factors) affecting tumor biology which are independent of
      tumor grade in these patients. A possible implication of this result is that
      complete surgical cytoreduction confers a survival benefit by producing a
      biologically more homogeneous tumor.

PMID- 10926798
TI  - Optimal cytoreductive surgery is an independent prognostic indicator in stage IV
      epithelial ovarian cancer with hepatic metastases.
AB  - OBJECTIVES: The aim of this study was to determine the value of optimal
      cytoreduction in stage IV epithelial ovarian cancer. METHODS: A retrospective
      review was performed of 37 women with stage IV epithelial ovarian cancer treated
      by radical surgery. RESULTS: Optimal surgery to less than 2 cm tumor deposits was
      performed in 16 of the 37 cases (43%) and tumor debulking to less than 1 cm tumor
      deposits in 6 cases (16.2%). Twenty-three cases (62%) were designated stage IV
      because of the presence of liver metastases alone. Although no patients died
      within 2 weeks of surgery, 7 of the 37 cases (22%) failed to survive more than 50
      days after primary surgery. The overall median survival was 11 months with
      overall 2- and 5-year survivals of 23 and 9%, respectively. On multivariate
      analysis comparing age, histological type, tumor grade, place of surgery,
      secondary surgical procedure, performance of bowel surgery, presence of liver
      metastases, and optimal cytoreduction, only optimal surgery and residual tumor
      deposits of less than 2 cm, or less than 1 cm, remained highly significant (P =
      0.0029 and 0.0086, respectively). Even when assessing only the 27 cases who were
      designated as having stage IV disease because of the presence of liver
      metastases, by multivariate analysis, only optimal surgery and residual tumor
      deposits of less than 2 cm, or less than 1 cm, remained significant (P = 0.023
      and 0.036, respectively). Site of metastases designating stage IV status was not
      associated with a reduced likelihood of achieving optimal debulking (P = 0.18).
      CONCLUSION: Optimal cytoreduction in women with stage IV epithelial ovarian
      cancer with or without hepatic metastases is associated with a more favorable
      outcome survival.

PMID- 10926800
TI  - Endometrial histopathology in 700 patients treated with tamoxifen for breast
      cancer.
AB  - OBJECTIVE: The aim of this study was the evaluation of endometrial
      histopathologic findings from 700 patients treated with tamoxifen (Tx) for breast
      cancer from two medical centers (United States and France). METHODS: A
      retrospective review of data including histologic slides from 134 hysterectomies
      and 566 endometrial biopsies from Tx-treated patients who presented with abnormal
      vaginal bleeding and/or abnormal sonograms was performed. Analysis of histologic
      characteristics included inactive/atrophic and functional endometria, endometrial
      polyps, hyperplasia and metaplasia, and endometrial cancer. Duration of Tx
      therapy was recorded when available, and its correlation with endometrial
      pathology was assessed. RESULTS: The only statistically significant difference
      between the data from the United States and France was the number of
      hysterectomies, which was almost double in France (27% vs 13.7%). Nonpathologic
      endometria made up 61.14% (inactive/atrophic 46%, functional 15.14%). Pathologic
      changes were found in 39.86% cases, of which polyps were 23.14%, glandular
      hyperplasia 8%, and metaplasia 3%; endometrial cancer made up 4.71% (33 cases).
      Nine cancers were well-differentiated endometrioid adenocarcinomas, and 24 were
      moderately or poorly differentiated, of which 13 had nonendometrioid components
      (serous, clear cell, MMMT). Fifteen cancers were found in endometrial polyps; 12
      were invasive to the myometrium and 4 to blood vessels. The weight of the uteri
      exceeded 300 g in 15 cases, with 4 exceeding 900 g. The average age of all
      patients was 60.91 years and of the cancer patients alone it was 69.26 years. The
      shortest average duration of Tx therapy (2.5 years) was found in patients with
      inactive/atrophic endometria and the longest (6.8 years) in patients with
      endometrial cancer. Patients with endometrial polyps and cancer presented more
      often with abnormal vaginal bleeding than those with inactive/atrophic
      endometrium. CONCLUSIONS: Most Tx-treated patients had no pathologic endometrial
      changes. Endometrial polyps, hyperplasia, and metaplasia, consistent with an
      estrogen-agonist effect of Tx, were found in roughly one-third of all patients.
      The endometrial cancers were often high-grade and invasive tumors. Patients with
      endometrial pathology were more often symptomatic than patients with
      inactive/atrophic endometria.

PMID- 10926801
TI  - Posttherapy surveillance of women with cervical cancer: an outcomes analysis.
AB  - OBJECTIVE: The aim of this study was to develop a surveillance program that
      optimizes clinical outcome following primary treatment of women with cervical
      cancer. METHODS: The records of 1096 patients with FIGO stage IB cervical cancer
      treated from 1983 to 1993 were retrospectively reviewed. Recurrence was analyzed
      by site, presence or absence of symptoms, method of detection, and survival.
      Univariate and multivariate analyses using a Cox proportional hazards model were
      performed. RESULTS: One hundred thirty-three patients (13%) developed recurrent
      disease. Of these, 114 were symptomatic and 19 were asymptomatic at the time of
      recurrence. Thirty-seven patients recurred in the central pelvis, 21 each in the
      lung or pelvic wall, 22 in nodes, and 35 in other sites. The median disease-free
      interval was 17 months for symptomatic patients and 16 months for asymptomatic
      patients. The median survival from initial diagnosis was 31 months for
      symptomatic and 83 months for asymptomatic patients (P = 0.001). The median
      survival from recurrence was 11 months for symptomatic and 42 months for
      asymptomatic patients (P < 0.001). Multivariate analysis revealed that symptom
      status at time of recurrence was a significant predictor of survival, even when
      known prognostic factors were considered (P < 0.001). All asymptomatic pelvic
      recurrences were diagnosed by pelvic exam; all asymptomatic pulmonary recurrences
      were detected by chest radiographs. Pap smears did not detect a single
      asymptomatic recurrence. CONCLUSIONS: Posttherapy surveillance programs are
      directed toward asymptomatic patients in whom early detection of recurrence may
      impact survival. These data indicate that a subset of women may benefit from
      surveillance. A model for surveillance is proposed.

PMID- 10926802
TI  - Luteinizing hormone-releasing hormone agonist triptorelin and antagonist
      cetrorelix inhibit EGF-induced c-fos expression in human gynecological cancers.
AB  - OBJECTIVES: Spontaneous and epidermal growth-factor-induced proliferation of
      human gynecological cancer cell lines is dose- and time-dependently reduced by
      treatment with the luteinizing hormone-releasing hormone (LHRH) agonist
      triptorelin and antagonist Cetrorelix. This antiproliferative activity is
      probably directly mediated through the LHRH receptors expressed by the tumor
      cells interacting with growth-factor-dependent mitogenic signal transduction. We
      have examined whether epidermal growth-factor (EGF)-induced expression of the
      early response gene c-fos is reduced by LHRH analogs. METHODS: Human endometrial
      (Ishikawa, Hec-1A), ovarian (EFO-21, EFO-27, SK-OV-3), and breast cancer cell
      lines (MCF-7) were rendered quiescent by incubation (72 h) in the absence of
      fetal calf serum and phenol red. This was followed by a 15-min incubation in the
      absence or presence of the LHRH agonist triptorelin (100 nM) or the antagonist
      Cetrorelix (100 nM) before the cells were stimulated for 10 min with EGF (100
      nM). C-fos mRNA expression was determined by semi-quantitative RT-PCR using a
      synthetic DNA fragment as internal standard. C-Fos protein synthesis was
      determined by SDS-PAGE and semi-quantitative Western blotting. RESULTS: In cells
      derived from endometrial and ovarian cancer, maximal c-fos mRNA expression (seven
      to ninefold over basal level) was obtained 30 min after EGF stimulation. In the
      breast cancer cell line MCF-7 this effect was obtained 60 min after EGF
      treatment. In all of the lines expressing LHRH receptor, EGF-induced c-fos mRNA
      expression as well as c-Fos protein synthesis was dose-dependently reduced by
      treatment with LHRH agonists and antagonists. At 100 nM concentrations of the
      LHRH analogs, c-fos expression was reduced to baseline levels. No effect of LHRH
      analogs on EGF-induced c-fos expression was observed in the ovarian cancer cell
      line SK-OV-3, which does not express the LHRH receptor. CONCLUSIONS: These
      results suggest that the binding of LHRH agonists and antagonists to their
      receptors inhibits the mitogenic signal transduction pathway of the EGF receptor
      in endometrial, ovarian, and breast cancer cell lines. The coupling of both
      signal transduction systems mediates the antiproliferative effect of LHRH
      analogs.

PMID- 10926803
TI  - Stage 3B adenocarcinoma of the endometrium: a clinicopathologic study.
AB  - OBJECTIVE: The aims of this study were to evaluate the management of Stage IIIB
      adenocarcinoma of the endometrium (EAC) and to determine the utility of the FIGO
      classification as it applies to patients with this category of disease and make
      recommendations on management. METHODS: A retrospective review was undertaken of
      the database of the Queensland Centre for Gynaecological Cancer (QCGC) from
      January 1982 to December 1996. The records of all patients recorded as having
      Stage IIIB EAC were retrieved. After validation of the designated staging, the
      contemporary disease status was determined and clinicopathological details were
      extracted from case notes. RESULTS: Of a total of 1940 patients with EAC treated
      by QCGC over the 15-year study period, 14 (0.7%) patients met the inclusion
      criteria. Nine patients (64%) presented with postmenopausal bleeding and the
      remaining patients presented with a variety of symptoms. There was no
      statistically significant difference in age between the study group and other
      patients with advanced stage EAC ranging from Stage IIIA to Stage IVB disease.
      Survival of patients with Stage IIIB disease was statistically significantly
      worse than that of patients with Stage IIIA disease, but was not statistically
      significantly different from patients with Stage IIIC, IVA, or IVB. While all
      patients had the unifying characteristic of metastatic disease in the vagina, the
      true extent of disease could not be determined by a full surgical staging
      procedure. Such optimal surgery was contraindicated in all patients because of
      the presence of significant coexisting medical conditions. Consequently,
      treatment was highly individualized. CONCLUSIONS: Stage IIIB adenocarcinoma of
      the endometrium is an uncommon condition. Similar to other substages of advanced
      disease, it is associated with a poor prognosis and requires individualized
      management. The argument is presented that this substage could be eliminated and
      included with Stage IIIC disease.

PMID- 10926804
TI  - Continent urinary diversion and low-rectal anastomosis in patients undergoing
      exenterative procedures for recurrent gynecologic malignancies.
AB  - OBJECTIVE: The aim of this study was to review the complications associated with
      continent urinary diversion and associated procedures in patients with
      gynecologic malignancies. METHODS: We retrospectively reviewed the medical
      records of all patients who underwent construction of a continent urinary conduit
      between October 1991 and October 1998 on the Gynecology Service at Memorial Sloan
      Kettering Cancer Center. RESULTS: Thirty-three patients were identified, of whom
      22 underwent total pelvic exenteration, 8 underwent anterior exenteration, and 3
      underwent urinary diversion procedures only. Complications associated with the
      urinary diversion procedure included ureteral strictures (2), pouch leakage (2),
      mild hydronephrosis, (6), pyelopnephritis (2), nocturnal incontinence (5), and
      difficulty with self-catheterization (2). Additional procedures performed
      concomitantly with continent urinary diversion and exenteration included pelvic
      reconstruction (18), low-rectal anastomosis (13), and intraoperative radiation
      therapy (9). The most significant morbidity was seen in patients undergoing
      concomitant low-rectal anastomosis, in whom the rate of anastomotic leaks was 54%
      (7 of 13 patients). CONCLUSIONS: Continent urinary diversion can successfully be
      accomplished at the time of exenteration in patients with recurrent gynecologic
      malignancies. The rate of major complications related to the urinary diversion is
      small and most complications can be managed nonsurgically. The greater than 50%
      rate of anastomotic leaks in patients undergoing concomitant low-rectal
      anastamosis suggests that such anastomosis should not be undertaken in this group
      of patients.

PMID- 10926806
TI  - Prospective management of stage IA(1) cervical adenocarcinoma by conization alone
      to preserve fertility: a preliminary report.
AB  - OBJECTIVE: Microinvasive cervical adenocarcinoma has an excellent prognosis and
      emerging data support the hypothesis that it should be treated in the same way as
      its squamous counterpart. We report our preliminary experience prospectively
      treating stage IA(1) cervical adenocarcinoma by conization alone in women who
      strongly desired to preserve their fertility. METHODS: Since May 1998, all
      patients with stage IA(1) cervical adenocarcinoma who expressed a strong desire
      to preserve fertility have been offered cold knife conization (CKC) and careful
      surveillance without hysterectomy. Women with lesions identifiable only
      microscopically, up to 3 mm invasive depth, up to 7 mm tumor width, and a
      conization specimen including the entire lesion with negative margins were
      eligible for conservative management. Postconization surveillance consisted of a
      Pap smear and endocervical curettage every 4 months. Medical records were
      reviewed for clinical data, follow-up, and disease status. RESULTS: Five women
      ages 26-33 elected CKC and surveillance. Four were nulliparous and one
      primiparous. Four tumors were endocervical cell type; one was adenosquamous.
      Three were grade 1, one was grade 2, and one grade 3. None had lymph-vascular
      space invasion. None of the patients has developed recurrent disease after 6-20
      months of follow-up. CONCLUSIONS: Our preliminary data suggest that patients with
      FIGO stage IA(1) cervical adenocarcinoma who strongly desire to preserve their
      fertility may be treated by conization alone if they are fully informed of the
      unknown risks for disease recurrence and are carefully followed. A multicenter
      trial is the next logical step to test the efficacy of this approach.

PMID- 10926805
TI  - A phase II trial of anastrozole in advanced recurrent or persistent endometrial
      carcinoma: a Gynecologic Oncology Group study.
AB  - BACKGROUND: Some endometrial cancers are hormonally dependent. A principal source
      of circulating estrogen is conversion of adrenal androstenedione by aromatase.
      Anastrozole (Arimidex) is an oral nonsteroidal aromatase inhibitor which is
      active in recurrent breast cancer. This Phase II study was undertaken to evaluate
      anastrozole in recurrent endometrial carcinoma. METHODS: Patients with advanced
      or recurrent endometrial cancer not curable with either surgery or radiation
      therapy and with measurable disease, a GOG (Zubrod) performance status of < or =
      2, no more than one prior hormonal therapy regimen, and no prior chemotherapy
      were eligible. Anastrozole was administered at a dose of 1 mg/day orally for at
      least 28 days. RESULTS: Twenty-three patients were entered on this trial. On
      central pathology review, 9 of them had grade 2 and 14 had grade 3 tumors. One to
      24 courses (median: 1) of therapy were administered. Two partial responses were
      noted (9%; 90% confidence interval 3 to 23%). Two additional patients had short
      term stable disease. With the exception of 1 case of venous thrombosis, the
      toxicity profile was mild. Median durations of progression-free survival and
      overall survival are 1 and 6 months, respectively. CONCLUSIONS: Anastrozole has
      minimal activity in an unselected population of patients with recurrent
      endometrial cancer.

PMID- 10926807
TI  - Safety and efficacy of adjuvant single-agent ifosfamide in uterine sarcoma.
AB  - PURPOSE: The role of adjuvant therapy for completely resected uterine sarcoma
      continues to be debated. Previous chemotherapy trials have shown little, if any,
      advantage over surgery alone, with significant added toxicity. To our knowledge,
      the current study is the first to evaluate adjuvant ifosfamide in completely
      resected uterine sarcomas. METHODS: Between 1992 and 1999, 13 consecutive
      patients with completely resected moderate- to high-grade uterine sarcoma
      received three cycles of adjuvant ifosfamide (1.5 g/m(2)/day x 3 days, repeated
      every 28 days). Mesna was given 30 min prior to infusion. Postinfusion mesna was
      administered to 10 of the patients in the outpatient setting utilizing a
      subcutaneous infusion pump. The remaining 3 patients received traditional
      intravenous mesna at 4 and 8 h after infusion. RESULTS: The median follow-up of
      the patient population was 26 months. For early-stage patients (n = 10), the 2
      year progression-free survival was 60%, with a median of 26 months. The 2-year
      overall survival was 100%, dropping to 67% at 3 years. Early-stage patients
      showed an advantage in both progression-free and overall survival. Early-stage
      patients with mixed mullerian tumor (MMT) had a significantly longer time to
      progression that those with leiomyosarcoma (LMS) (2-year progression-free
      survival of 100% versus 33%; P = 0.019). Three patients required dose reduction
      secondary to grade 2-3 toxicities (neutropenia x2, nausea and vomiting x1). All
      significant toxicity was eliminated with dose reduction. CONCLUSIONS: Adjuvant
      ifosfamide appears to be safe and well tolerated in patients with completely
      resected uterine sarcoma. It can easily be given in the outpatient setting if
      mesna is administered via a subcutaneous pump. Our data, consistent with previous
      studies in advanced sarcoma, suggest a potentially greater role for ifosfamide in
      MMT than in LMS.

PMID- 10926808
TI  - A phase II and pharmacokinetic study of weekly 72-h topotecan infusion in
      patients with platinum-resistant and paclitaxel-resistant ovarian carcinoma.
AB  - BACKGROUND: As suggested by preclinical trials, prolonged administration of
      topotecan, a reversible inhibitor of topoisomerase-I, may have a therapeutic
      advantage. Following a phase I trial of weekly 72-h topotecan infusion, we
      performed a phase II trial utilizing this schedule in ovarian carcinoma. METHODS:
      Eligibility included platinum-/paclitaxel-resistant ovarian carcinoma, measurable
      disease, and adequate hematologic, renal, and hepatic function. A dose of 2.0
      mg/m(2) of topotecan was administered as a 72-h infusion weekly via an ambulatory
      pump. Plasma topotecan concentrations were determined prior to and at the
      completion of each weekly course. RESULTS: Twenty-four patients were entered and
      23 patients were evaluable for toxicity and response. Two hundred eighteen weekly
      courses of therapy were administered (median 7 weeks, range 4-46 weeks). Toxicity
      was mild with grade 3 leukopenia, neutropenia, and anemia occurring in 13, 13,
      and 17% of patients, respectively. Two of 23 patients (9.1%) (CI 1-28%) had
      partial responses of 2 and 3 months' duration and 6 had stable disease. Steady
      state plasma topotecan lactone concentrations were a median of 1.2 ng/ml (range
      0.4-8.00 ng/ml) following the first week of infusion. Steady state topotecan
      lactone concentrations after the first week of infusion were highest in 2
      patients with partial responses. Mean steady state plasma topotecan lactone
      concentrations after the first week of infusion were 4.6, 2.0, and 1.3 ng/ml for
      partial response, stable disease, and progressive disease, respectively. An
      analysis of variance of steady state plasma topotecan concentrations after the
      first week of infusion over all administered cycles demonstrated a significant
      difference in steady state plasma topotecan lactone concentrations between
      patients with partial response and stable disease and between partial response
      and no response (significant at the 0.05 level after adjustment for multiple
      comparisons). Controlling for cycle number, steady state topotecan lactone
      concentrations are significantly greater for patients with responding or stable
      disease than those with progressive disease (P = 0.0003) and have a lower bound
      of > or = 1.9 ng/ml (95% confidence level). CONCLUSION: Steady state topotecan
      lactone concentrations are associated with responding or stable disease in
      platinum- and paclitaxel-resistant ovarian cancer. Steady state topotecan
      concentrations could potentially be utilized to modify tumor exposure and
      response.

PMID- 10926809
TI  - Cavitational ultrasonic surgical aspiration for the treatment of vaginal
      intraepithelial neoplasia.
AB  - OBJECTIVE: The aim of this study is to determine whether cavitational ultrasonic
      surgical aspiration (CUSA) is effective and safe for treating vaginal
      intraepithelial neoplasia (VAIN). METHODS: We conducted a retrospective chart
      review of 46 patients who were treated with CUSA for VAIN in a single gynecologic
      oncology practice between 1981 and 1999. RESULTS: At initial presentation, 39% of
      treated patients had grade I VAIN, 20% had grade II, and 41% had grade III. The
      mean duration of follow-up from initial CUSA treatment was 21 months. Twenty-nine
      patients (63%) were initially treated with CUSA, 7 patients (15%) with laser
      vaporization, 7 patients (15%) with surveillance by Papanicolaou smear, 1 patient
      (2%) with partial vaginectomy, 1 patient (2%) with 5-fluorouracil, and 1 patient
      (2%) with loop excision. Patients initially treated with CUSA had a higher
      percentage of grade III VAIN at diagnosis (48%) than did patients initially
      treated with other methods (29%). A significantly greater proportion of patients
      initially treated with CUSA had no recurrence of VAIN (66%) compared with
      patients initially treated with other methods (0%) (P < 0.0001). A significantly
      greater proportion of patients who were treated for recurrent disease with CUSA
      had no further recurrence (52%) compared with patients treated for recurrent
      disease with other methods (9%) (P < 0.001). No patient treated with CUSA
      reported adverse effects; 7 patients treated with other methods reported dysuria,
      burning, and pain. CONCLUSION: These initial data suggest that CUSA is a safe and
      effective method for treating VAIN and may be an appropriate treatment for many
      patients.

PMID- 10926810
TI  - Benign mullerian inclusions in pelvic and paraaortic lymph nodes.
AB  - OBJECTIVE: This study was undertaken to determine the incidence and distribution
      of the location of benign mullerian inclusions in pelvic and paraaortic lymph
      nodes. METHODS: A total of 114 patients operated on for gynecologic malignancy
      between 1995 and 1998 underwent surgery including systematic pelvic (n = 114) or
      pelvic and paraaortic (n = 70) lymphadenectomy. The lymph node material was
      labeled according to anatomic origin, immediately fixed en bloc, embedded in
      paraffin, and processed as step-serial sections at intervals of 400 microm. The 5
      microm-thick sections were stained with hematoxylin and eosin. RESULTS: Overall,
      26 of 114 patients (23%) had benign mullerian inclusions. Inclusions were most
      common in the paraarotic (34%), external iliac (12%), and common iliac (9%)
      regions (P > 0.05). Multiple anatomic sites were involved in 14 of 26 patients
      (54%). Two women had paraaortic inclusions and negative pelvic nodes. Benign
      mullerian inclusions were seen in 13 of 51 patients (24%) with ovarian carcinoma,
      11 of 47 (23%) with cervical carcinoma, 1 of 9 (11%) with endometrial carcinoma,
      and 1 of 2 with ovarian serous borderline tumor, (P > 0.05). CONCLUSIONS: Benign
      mullerian inclusions occur in approximately one-fifth of patients with
      gynecologic malignancies in all anatomic regions of pelvic and paraaortic lymph
      nodes. They must be distinguished from metastatic deposits.

PMID- 10926811
TI  - Significance of atypical glandular cells of undetermined significance on ThinPrep
      Papanicolaou smears.
AB  - OBJECTIVE: The aim of this study was to assess the incidence and risk factors
      predictive of significant histopathologic findings among women with atypical
      glandular cells of undetermined significance (AGCUS) on ThinPrep Papanicolaou
      smears. METHODS: ThinPrep smears with AGCUS obtained between 1997 and 1999 were
      reviewed. Patients' charts were reviewed and patients' characteristics, follow-up
      information, and colposcopy and biopsy results were recorded. Pathologic slides
      were reviewed. The demographic features of women with favor reactive smears were
      compared with those with favor neoplasia and risk factors predictive of
      significant histopathologic findings (high-grade squamous intraepithelial lesion,
      endometrial hyperplasia, and cervical or endometrial cancers) were calculated.
      RESULTS: The rate of diagnosis of AGCUS was 0.65%. Eighty-four patients with
      follow-up information were identified. The demographic features of women with
      smears favor neoplasia (n = 43) were similar to those with smears favor reactive
      (n = 41). The rates of incidence of any dysplasia or cancer and significant
      histopathologic findings were 32.1 and 22.6%, respectively, and were higher among
      women with smears favor neoplasia than among women with smears favor reactive
      (41.9% versus 22.0%, P = 0.051, and 34.9% versus 9.8%, P = 0.006, respectively).
      The subtype of cytology was the only factor that predicted significant
      histopathologic findings (odds ratio = 5.0, 95% confidence interval 1.6, 15.6, P
      < 0.010). CONCLUSIONS: In women with AGCUS on ThinPrep smears, significant
      histopathologic findings were found in 34.9% versus 9.8%, depending on the
      subtype of the smear (favor neoplasia vs reactive). Further studies are needed to
      validate the cytologic criteria for subtyping AGCUS smears and base management of
      women with AGCUS cytology on the subtype of the smear.

PMID- 10926812
TI  - Langerhans' cell histiocytosis on the vulva.
AB  - BACKGROUND: Langerhans' cell histiocytosis (LCH) affecting the vulva alone is
      rare. At present, there are 51 published cases of LCH affecting the genital area.
      Of these, only 7 had LCH located in the genital area alone; in these cases, there
      was no subsequent systemic spread of the disease. A report of the 8th such case
      is presented with a review of the previous 7 cases. CASE: A 40-year-old white
      woman presented with a several-month history of pruritic and ulcerous lesions on
      the vagina which had then spread to the vulva. No tiredness, general malaise, or
      associated temperature was observed. Physical examination disclosed an
      erythematous plaque on the labia minora, which was bilateral and slightly
      infiltrated. The rest of the physical examination brought no other disorders of
      interest to light. Histological findings were characteristic of LCH. Four cycles
      of iv vincristine (2 mg/m cycle) 15 days apart did not obtain objective or
      symptomatic improvement in the vulvar lesions. Therefore, a local and partial
      extirpation of both labia minora was performed. Eighteen months after surgery,
      the patient has no symptoms or signs of local recurrence or systemic spread.
      CONCLUSIONS: Although the occurrence of LCH on the vulva is very unusual, we must
      bear this possibility in mind when a woman presents atypical chronic lesions on
      the genital mucosa. In such cases, it is necessary to perform a biopsy on the
      mucosa, rule out the possibility of systemic disease, and review the patient
      periodically in order to forestall a possible spread of the disease at any time.

PMID- 10926813
TI  - Jejunal adenocarcinoma presenting as a primary ovarian carcinoma.
AB  - OBJECTIVE: The aim of this case report was to evaluate the impact of
      immunohistochemical markers in diagnosing the primary site of adenocarcinoma in
      the abdominopelvic region. METHODS: Surgicopathologic data were obtained from
      laparotomy and necropsy. Paraffin-embedded tissue from the ovary and jejunum was
      stained with hematoxylin and eosin, as well as with immunohistochemical stains
      for cytokeratin 20 and cytokeratin 7. RESULTS: A 53-year-old African American
      woman underwent an emergency laparotomy due to small bowel obstruction. During
      the operation, in addition to a complex adnexal mass as the cause of obstruction,
      a small solid jejunal tumor was also identified. Pathologic evaluation of the two
      sites demonstrated an infiltrating moderately to poorly differentiated
      adenocarcinoma with mucinous features. The malignant cells from both intestinal
      and ovarian sites showed immunoreactivity for cytokeratin 20 and revealed
      negative staining for cytokeratin 7. These results confirmed the diagnosis of
      intestinal primary with ovarian metastasis, which was initially misdiagnosed as
      an ovarian primary. CONCLUSION: Given the potential difficulty in determining the
      primary site of these tumors, immunohistochemistry proved to be a useful tool in
      reaching the correct diagnosis.

PMID- 10926814
TI  - Docetaxel extravasation causing significant delayed tissue injury.
AB  - PURPOSE: Docetaxel is a relatively new taxane that has not been associated with
      significant tissue injury after extravasation. We present a case of a patient who
      had grade 4 tissue toxicity after extravasation of docetaxel infused through a
      peripheral intravenous site. CASE REPORT: A 71-year-old female was being treated
      for recurrent ovarian cancer with docetaxel and carboplatin. Shortly after the
      docetaxel infusion began, she experienced docetaxel extravasation into the dorsum
      of her left hand. The infusion was halted, and then the administration was
      continued in a peripheral intravenous site in the other upper extremity. Erythema
      was noted by the patient on the dorsum of her left hand 6 days after
      infiltration. The following day, the patient noted severe pain, decreased
      function, and blistering along with increased erythema. The patient presented to
      the gynecology oncology clinic 11 days after the extravasation injury occurred.
      Conservative management was undertaken, and over the next 4 weeks the patient had
      resolution of the skin changes and full return of function. CONCLUSION: Docetaxel
      can cause significant delayed tissue injury if extravasation occurs.

PMID- 10926815
TI  - Limits to the "benefits" from our oncologic interventions: a case report.
AB  - PURPOSE: The aim of this study was to discuss the potential implications of
      prolonged and aggressive treatment of long-term survivors of ovarian cancer.
      METHODS: A case report of a patient with ovarian cancer extensively treated with
      platinum-based chemotherapy and aggressive surgery is presented. RESULTS: A woman
      with a >15-year history of ovarian cancer experienced severe neurotoxicity
      (peripheral neuropathy, hearing loss), underwent aggressive resection of
      asymptomatic and long-standing metastatic disease in the liver (with tumor
      recurrence <1 year after surgery), and subsequently died of secondary acute
      leukemia. CONCLUSION: It is critical that oncologists remember that the
      theoretical benefits of available anti-neoplastic interventions must be carefully
      and constantly weighted against the potential harm they may cause.

PMID- 10926817
TI  - Reply

PMID- 10926816
TI  - Fallopian tube cancer as a feature of BRCA1-associated syndromes.

PMID- 10926818
TI  - Weekly carboplatin as a strategy to prevent severe treatment-related emesis.

PMID- 10926820
TI  - Reply

PMID- 10926819
TI  - Endodermal sinus tumor in pregnancy.

PMID- 10926823
TI  - The influence of secretory-protein charge on late stages of secretion from the
      Gram-positive bacterium Bacillus subtilis.
AB  - Following their secretion across the cytoplasmic membrane, processed secretory
      proteins of Bacillus subtilis must fold into their native conformation prior to
      translocation through the cell wall and release into the culture medium. The rate
      and efficiency of folding are critical in determining the yields of intact
      secretory proteins. The B. subtilis membrane is surrounded by a thick cell wall
      comprising a heteropolymeric matrix of peptidoglycan and anionic polymers. The
      latter confer a high density of negative charge on the wall, endowing it with ion
      exchange properties, and secretory proteins destined for the culture medium must
      traverse the wall as the last stage in the export process. To determine the
      influence of charge on late stages in the secretion of proteins from this
      bacterium, we have used sequence data from two related alpha-amylases, to
      engineer the net charge of AmyL, an alpha-amylase from Bacillus licheniformis
      that is normally secreted efficiently from B. subtilis. While AmyL has a pI of
      7.0, chimaeric enzymes with pI values of 5.0 and 10.0 were produced and
      characterized. Despite the engineered changes to their physico-chemical
      properties, the chimaeric enzymes retained many of the enzymic characteristics of
      AmyL. We show that the positively charged protein interacts with the cell wall in
      a manner that influences its secretion.

PMID- 10926821
TI  - Signal-dependent membrane targeting by pleckstrin homology (PH) domains.
AB  - Pleckstrin homology (PH) domains are small protein modules of around 120 amino
      acids found in many proteins involved in cell signalling, cytoskeletal
      rearrangement and other processes. Although several different protein ligands
      have been proposed for PH domains, their only clearly demonstrated physiological
      function to date is to bind membrane phosphoinositides. The PH domain from
      phospholipase C-delta(1) binds specifically to PtdIns(4,5)P(2) and its headgroup,
      and has become a valuable tool for studying cellular PtdIns(4,5)P(2) functions.
      More recent developments have demonstrated that a subset of PH domains recognizes
      the products of agonist-stimulated phosphoinositide 3-kinases. Fusion of these PH
      domains to green fluorescent protein has allowed dramatic demonstrations of their
      independent ability to drive signal-dependent recruitment of their host proteins
      to the plasma membrane. We discuss the structural basis for this 3
      phosphoinoistide recognition and the role that it plays in cellular signalling.
      PH domains that bind specifically to phosphoinositides comprise only a minority
      (perhaps 15%) of those known, raising questions as to the physiological role of
      the remaining 85% of PH domains. Most (if not all) PH domains bind weakly and non
      specifically to phosphoinositides. Studies of dynamin-1 have indicated that
      oligomerization of its PH domain may be important in driving membrane
      association. We discuss the possibility that membrane targeting by PH domains
      with low affinity for phosphoinositides could be driven by alteration of their
      oligomeric state and thus the avidity of their membrane binding.

PMID- 10926822
TI  - RGS14 is a novel Rap effector that preferentially regulates the GTPase activity
      of galphao.
AB  - In an attempt to elucidate the physiological function(s) of the Ras-related Rap
      proteins, we used the yeast two-hybrid system and isolated a cDNA encoding a
      protein that interacts with both Rap1 and Rap2, but not with Ras; the use of Rap2
      mutants showed that this interaction is characteristic of a potential Rap
      effector. This protein was identified as RGS14, a member of the recently
      discovered family of RGS ('regulators of G-protein signalling') proteins that
      stimulate the GTPase activity of the GTP-binding alpha subunit of heterotrimeric
      G-proteins (Galpha). Deletion analysis, as well as in vitro binding experiments,
      revealed that RGS14 binds Rap proteins through a domain distinct from that
      carrying the RGS identity, and that this domain shares sequence identity with the
      Ras/Rap binding domain of B-Raf and Raf-1 kinases. RGS14 is distinguished from
      other RGS proteins by its marked preference for Galpha(o) over other Galpha
      subunits: RGS14 binds preferentially to Galpha(o) in isolated brain membranes,
      and also interacts preferentially with Galpha(o) (as compared with Galpha(i1)) to
      stimulate its GTPase activity. In adult mice, RGS14 expression is restricted to
      spleen and brain. In situ hybridization studies showed that it is highly
      expressed only in certain areas of mouse brain (such as the CA1 and CA2 regions
      of the hippocampus), and that this pattern closely resembles that of Rap2, but
      not Rap1, expression. Double in situ hybridization experiments revealed that
      certain cells in the hippocampus express both RGS14 and Galpha(o), as well as
      both RGS14 and Rap2, showing that the interaction of RGS14 with Galpha(o) and
      Rap2 is physiologically possible. Taken together, these results suggest that
      RGS14 could constitute a bridging molecule that allows cross-regulation of
      signalling pathways downstream from G-protein-coupled receptors involving
      heterotrimeric proteins of the G(i/o) family and those involving the Ras-related
      GTPase Rap2.

PMID- 10926824
TI  - Band 3 mutations, renal tubular acidosis and South-East Asian ovalocytosis in
      Malaysia and Papua New Guinea: loss of up to 95% band 3 transport in red cells.
AB  - We describe three mutations of the red-cell anion exchangerband 3 (AE1, SLC4A1)
      gene associated with distalrenal tubular acidosis (dRTA) in families from
      Malaysia and Papua NewGuinea: Gly(701)-->Asp (G701D), Ala(858)-->Asp(A858D) and
      deletion of Val(850) (DeltaV850). The mutationsA858D and DeltaV850 are novel; all
      three mutations seem to berestricted to South-East Asian populations. South-East
      Asianovalocytosis (SAO), resulting from the band 3 deletion of residues400-408,
      occurred in many of the families but did not itselfresult in dRTA. Compound
      heterozygotes of each of the dRTA mutationswith SAO all had dRTA, evidence of
      haemolytic anaemia and abnormal red-cell properties. The A858D mutation showed
      dominant inheritance and therecessive DeltaV850 and G701D mutations showed a
      pseudo-dominantphenotype when the transport-inactive SAO allele was also present.
      Red-cell and Xenopus oocyte expression studies showed that theDeltaV850 and A858D
      mutant proteins have greatly decreased aniontransport when present as compound
      heterozygotes (DeltaV850/A858D,DeltaV850/SAO or A858D/SAO). Red cells with
      A858D/SAO had only 3% ofthe SO(4)(2-) efflux of normal cells, thelowest anion
      transport activity so far reported for human red cells. The results suggest dRTA
      might arise by a different mechanism for eachmutation. We confirm that the G701D
      mutant protein has an absoluterequirement for glycophorin A for movement to the
      cell surface. Wesuggest that the dominant A858D mutant protein is possibly mis
      targetedto an inappropriate plasma membrane domain in the renal tubular cell,and
      that the recessive DeltaV850 mutation might give dRTA because ofits decreased
      anion transport activity.

PMID- 10926825
TI  - Red-cell glycophorin A-band 3 interactions associated with the movement of band 3
      to the cell surface.
AB  - We have examined the mechanism by which glycophorin A (GPA) facilitates the
      movement of the human red-cell anion exchanger (band 3, AE1) to the cell surface.
      GPA itself forms stable dimers in membranes and detergent solution. Four mutants
      of human GPA with impaired dimerization were prepared (L75I, I76A, G79L and
      G83L). All four GPA mutants enhanced band 3 translocation to the Xenopus oocyte
      plasma membrane in the same way as wild-type GPA, showing that the GPA monomer is
      sufficient to mediate this process. Cell-surface expression of the natural band 3
      mutant G701D has an absolute requirement for GPA. GPA monomers also rescued the
      cell-surface expression of this mutant band 3. Taking into account other
      evidence, we infer that the site of GPA interaction with band 3 is located
      outside the GPA dimerization interface but within the GPA transmembrane span. The
      results of examination of the cell-surface expression of GPA and band 3 in
      different K562 erythroleukaemia cell clones stably transfected with band 3 are
      consistent with the movement of GPA and band 3 to the cell surface together. We
      discuss the pathways by which band 3 moves to the cell surface in the presence
      and the absence of GPA, concluding that GPA has a role in enhancing the folding
      and maturation of band 3. We propose that GPA functions in erythroid cells to
      assist with the incorporation of large amounts of properly folded band 3 into the
      membrane within a limited time span during erythroid maturation.

PMID- 10926826
TI  - Malonyl-CoA metabolism in cardiac myocytes.
AB  - (1) Malonyl-CoA is thought to play a signalling role in fuel-selection in cardiac
      muscle, but the rate at which the concentration of this potential signal can be
      changed has not previously been investigated. (2) Rapid changes in cellular
      malonyl-CoA could be observed when rat cardiac myocytes were incubated in glucose
      free medium followed by re-addition of 5 mM glucose, or when cells were
      transferred from a medium containing glucose to a glucose-free medium. On
      addition of glucose, malonyl-CoA increased by 62% to a new steady-state level, at
      a rate of at least 0.4 nmol/g dry wt. per min. The half-time of this change was
      less than 3 min. After removal of glucose the malonyl-CoA content was estimated
      to decline by 0.43-0.55 nmol/g dry wt. per min. (3) Malonyl-CoA decarboxylase
      (MDC) is a possible route for disposal of malonyl-CoA. No evidence was obtained
      for a cytosolic activity of MDC in rat heart where most of the activity was found
      in the mitochondrial fraction. MDC in the mitochondrial matrix was not accessible
      to extramitochondrial malonyl-CoA. However, approx. 16% of the MDC activity in
      mitochondria was overt, in a manner that could not be explained by mitochondrial
      leakage. It is suggested that this, as yet uncharacterized, overt MDC activity
      could provide a route for disposal of cytosolic malonyl-CoA in the heart. (4) No
      activity of the condensing enzyme for the fatty acid elongation system could be
      detected in any heart subcellular fraction using two assay systems. A previous
      suggestion [Awan and Saggerson (1993) Biochem. J. 295, 61-66] that this could
      provide a route for disposal of cytosolic malonyl-CoA in heart should therefore
      be abandoned.

PMID- 10926827
TI  - Mutagenesis studies on the sensitivity of Escherichia coli acetohydroxyacid
      synthase II to herbicides and valine.
AB  - Acetohydroxyacid synthase (EC 4.1.3.18, also known as acetolactate synthase)
      isoenzyme II from Escherichia coli is inhibited by sulphonylurea and
      imidazolinone herbicides, although it is much less sensitive than the plant
      enzyme. This isoenzyme is also unusual in that it is not inhibited by valine.
      Mutating S100 (Ser(100) in one-letter amino acid notation) of the catalytic
      subunit to proline increases its sensitivity to sulphonylureas, but not to
      imidazolinones. Mutating P536 to serine, as found in the plant enzyme, had little
      effect on the properties of the enzyme. Mutating E14 of the regulatory subunit to
      glycine, either alone or in combination with the H29N (His(29)-->Asn) change, did
      not affect valine-sensitivity.

PMID- 10926828
TI  - Characterization of derivatives of the high-molecular-mass penicillin-binding
      protein (PBP) 1 of Mycobacterium leprae.
AB  - Mycobacterium leprae has two high-molecular-mass multimodular penicillin-binding
      proteins (PBPs) of class A, termed PBP1 and PBP1* [Lepage, Dubois, Ghosh, Joris,
      Mahapatra, Kundu, Basu, Chakrabarti, Cole, Nguyen-Disteche and Ghuysen (1997) J.
      Bacteriol. 179, 4627-4630]. PBP1-Xaa-beta-lactamase fusions generated periplasmic
      beta-lactamase activity when Xaa (the amino acid of PBP1 at the fusion junction)
      was residue 314, 363, 407, 450 or 480. Truncation of the N-terminal part of the
      protein up to residue Leu-147 generated a penicillin-binding polypeptide which
      could still associate with the plasma membrane, whereas [DeltaM1-R314]PBP1 (PBP1
      lacking residues Met-1 to Arg-314) failed to associate with the membrane,
      suggesting that the region between residues Leu-147 and Arg-314 harbours an
      additional plasma membrane association site for PBP1. Truncation of the C
      terminus up to 42 residues downstream of the KTG (Lys-Thr-Gly) motif also
      generated a polypeptide that retained penicillin-binding activity. [DeltaM1
      R314]PBP1 could be extracted from inclusion bodies and refolded under appropriate
      conditions to give a form capable of binding penicillin with the same efficiency
      as full-length PBP1. This is, to the best of our knowledge, the first report of a
      soluble derivative of a penicillin-resistant high-molecular-mass PBP of class A
      that is capable of binding penicillin. A chimaeric PBP in which the penicillin
      binding (PB) module of PBP1 was fused at its N-terminal end with the non
      penicillin-binding (n-PB) module of PBP1* retained pencillin-binding activity
      similar to that of PBP1, corroborating the finding that the n-PB module of PBP1
      is dispensable for its penicillin-binding activity.

PMID- 10926829
TI  - Effects of modification of the hydrophobic C-1-C-16 segment of tautomycin on its
      affinity to type-1 and type-2A protein phosphatases.
AB  - Among the naturally occurring toxins that are known to have specific inhibitory
      effects on type-1 and type-2A protein phosphatases (PP1 and PP2A), tautomycin
      (TM) is unique in that it exhibits significantly higher affinity to PP1 than to
      PP2A. The ratio of the dissociation constant for the PP1-TM interaction to that
      for the PP2A-TM interaction (the PP1/PP2A ratio) is 0.01-0.03. The aim of the
      present study was to evaluate the possible contributions of the C-1-C-16 segment
      of TM to the affinity characteristics of the toxin. The relatively hydrophobic
      segment contains a spiroketal motif whose enantiomeric form is present in okadaic
      acid (OA), which exhibits exceedingly higher affinity to PP2A than to PP1. We
      therefore synthesized two TM analogues: TM1 in which the side chains of the
      spiroketal motif of TM were removed but its absolute configuration was retained,
      and TM2 in which the spiroketal motif of TM1 was replaced with its enantiomeric
      form. The effects of TM, TM1 and TM2 on the activities of the native catalytic
      subunits of PP1 (PP1C) and PP2A and a recombinant gamma isoform of PP1 (PP1gamma)
      were examined. The PP1/PP2A ratio determined thereby was 0.2-0.5 for TM1 and 5-10
      for TM2. Both the presence of the side chains and the stereochemistry of the
      spiroketal moieties may be major determining factors for the affinity
      characteristics of TM. We also show that a monoclonal antibody raised against OA
      binds to TM2 albeit with much lower affinity than to OA, whereas it exhibits no
      measurable affinities to TM and TM1.

PMID- 10926830
TI  - Mutation of threonine-241 to proline eliminates autocatalytic modification of
      human carbonyl reductase.
AB  - Carbonyl reductase catalyses the reduction of steroids, prostaglandins and a
      variety of xenobiotics. An unusual property of human and rat carbonyl reductases
      is that they undergo modification at lysine-239 by an autocatalytic process
      involving 2-oxocarboxylic acids, such as pyruvate and 2-oxoglutarate. Comparison
      of human carbonyl reductase with the pig enzyme, which does not undergo
      autocatalytic modification, identified three sites, alanine-236, threonine-241
      and glutamic acid-246, on human carbonyl reductase that could be important in the
      reaction of lysine-239 with 2-oxocarboxylic acids. Mutagenesis experiments show
      that replacement of threonine-241 with proline (T241P) in human carbonyl
      reductase eliminates the formation of carboxyethyl-lysine-239. In contrast, the
      T241A mutant has autocatalytic activity similar to wild-type carbonyl reductase.
      The T241P mutant retains catalytic activity towards menadione, although with one
      fifth the catalytic efficiency of wild-type carbonyl reductase. Replacement of
      threonine-241 with proline is likely to disrupt the local structure near lysine
      239. We propose that integrity of this local environment is essential for
      chemical modification of lysine-239, but not absolutely required for carbonyl
      reductase activity.

PMID- 10926831
TI  - Peroxisome-proliferator-activated receptor delta mediates the effects of long
      chain fatty acids on post-confluent cell proliferation.
AB  - Nutritional long-chain fatty acids control adipose tissue mass by regulating the
      number and the size of adipocytes. It is now established that peroxisome
      proliferator-activated receptors (PPARs) play crucial functions in the control of
      gene expression and the level of cell differentiation. PPARgamma, which is
      activated by specific prostanoids, is a key factor in activating terminal
      differentiation and adipogenesis. We have recently demonstrated that PPARdelta,
      once activated by fatty acids, drives the expression of a limited set of genes,
      including that encoding PPARgamma, thereby inducing adipose differentiation. Thus
      far, the mechanism of action of fatty acids in the control of preadipocyte
      proliferation has remained unknown. We show here that PPARdelta is directly
      implicated in fatty acid-induced cell proliferation. Ectopic expression of
      PPARdelta renders 3T3C2 cells capable of responding to treatment with long-chain
      fatty acids by a resumption of mitosis, and this effect is limited to a few days
      after confluence. This response is restricted to PPARdelta activators and, for
      fatty acids, takes place within the range of concentrations found to trigger
      differentiation of preadipocytes both in vitro and in vivo. Furthermore, the use
      of a mutated inactive PPARdelta demonstrated that transcriptional activity of the
      nuclear receptor is required to mediate fatty acid-induced proliferation. These
      data demonstrate that PPARdelta, as a transcription factor, is directly
      implicated in fatty acid-induced proliferation, and this could explain the
      hyperplastic development of adipose tissue that occurs in high-fat-fed animals.

PMID- 10926832
TI  - The cytosolic C-terminus of the glucose transporter GLUT4 contains an acidic
      cluster endosomal targeting motif distal to the dileucine signal.
AB  - The insulin-responsive glucose transporter GLUT4 is targeted to a post-endocytic
      compartment in adipocytes, from where it moves to the cell surface in response to
      insulin. Previous studies have identified two cytosolic targeting motifs that
      regulate the intracellular sequestration of this protein: FQQI(5-8) in the N
      terminus and LL(489,490) (one-letter amino acid notation) in the C-terminus. In
      the present study we show that a GLUT4 chimaera in which the C-terminal 12 amino
      acids in GLUT4 have been replaced with the same region from human GLUT3 is
      constitutively targeted to the plasma membrane when expressed in 3T3-L1
      adipocytes. To further dissect this domain it was divided into three regions,
      each of which was mutated en bloc to alanine residues. Analysis of these
      constructs revealed that the targeting information is contained within the
      residues TELEYLGP(498-505). Using the transferrin-horseradish peroxidase
      endosomal ablation technique in 3T3-L1 adipocytes, we show that mutants in which
      this C-terminal domain has been disrupted are more sensitive to chemical ablation
      than wild-type GLUT4. These data indicate that GLUT4 contains a targeting signal
      in its C-terminus, distal to the dileucine motif, that regulates its sorting into
      a post-endosomal compartment. Similar membrane-distal, acidic-cluster-based
      motifs are found in the cytosolic tails of the insulin-responsive aminopeptidase
      IRAP (insulin-regulated aminopeptidase) and the proprotein convertase PC6B,
      indicating that this type of motif may play an important role in the endosomal
      sequestration of a number of different proteins.

PMID- 10926833
TI  - Responsiveness of the state of O-linked N-acetylglucosamine modification of
      nuclear pore protein p62 to the extracellular glucose concentration.
AB  - O-linked N-acetylglucosamine (O-GlcNAc) modification has been described in many
      proteins, including nuclear pore glycoproteins. In the present study we
      investigated the effect of extracellular glucose on the level of modification of
      nuclear pore protein p62 by O-GlcNAc. We found that exposure of cells to a high
      concentration of glucose caused an increased level of modification of p62 with O
      GlcNAc, whereas the modification of other proteins did not change detectably. The
      increased O-GlcNAc modification of p62 in response to glucose required the
      metabolism of glucose to glucosamine. The exposure of the cells to glucosamine
      itself also caused increased O-GlcNAc modification, whereas mannosamine and
      galactosamine did not. Furthermore, changes in glucose concentrations within the
      physiological range induced the O-GlcNAc modification in p62 in rat aortic smooth
      muscle cells, indicating that this modification of p62 might occur in an intact
      animal. These results imply that the ambient glucose concentration has an impact
      on the level of O-GlcNAc modification of proteins such as p62, and that
      functional changes in some of these proteins might ensue.

PMID- 10926834
TI  - cAMP attenuates interleukin-1-stimulated macrophage colony-stimulating factor (M
      CSF) expression.
AB  - Macrophage colony-stimulating factor (M-CSF) is a multifunctional cytokine
      attributed with key biological functions beyond the first discovered role in
      promoting proliferation of myeloid cell lineage. The human pancreatic cancer cell
      line MIA PaCa-2, from which the M-CSF gene was originally cloned, was used to
      study regulation of M-CSF expression. Expression of M-CSF was inducible by
      interleukin-1alpha (IL-1alpha), lipopolysaccharide (LPS) and PMA as demonstrated
      by a biological activity assay, Northern-blot analysis and reverse transcriptase
      (RT) PCR. Treatment of the cells with forskolin or dibutyryl-cAMP attenuated the
      expression of M-CSF induced by IL-1alpha or LPS, but not by PMA. Electromobility
      shift assays showed that IL-1alpha predominantly activated nuclear factor kappaB
      (NF-kappaB), while PMA preferentially activated activator protein-1 (AP-1). The
      activation of NF-kappaB, but not AP-1, could be attenuated by cAMP elevation.
      Relative RT-PCR demonstrated that the expression of a 1.6-kb M-CSF mRNA
      transcript was more effectively induced by IL-1alpha than a 4.0-kb transcript. By
      and large the induced expression of both mRNA transcripts could be attenuated by
      cAMP. M-CSF promoter-driven luciferase reporter-gene assays revealed that cAMP
      elevation attenuated the IL-1-induced transcription activation of the M-CSF
      promoter, but it had no effect on PMA-induced transcription. Our findings suggest
      that cAMP regulates M-CSF gene expression at the transcriptional level and that
      its inhibitory effect involves NF-kappaB signalling pathway.

PMID- 10926835
TI  - A natural sequence consisting of overlapping glucocorticoid-responsive elements
      mediates glucocorticoid, but not androgen, regulation of gene expression.
AB  - Cytosolic aspartate aminotransferase (cAspAT) is regulated by glucocorticoids in
      rat liver and kidney. Part of this regulation is mediated by an unusual
      glucocorticoid-responsive element (GRE)-like sequence called GRE A. GRE A is
      composed of two overlapping imperfect GREs, each comprising a conserved half-site
      (half-sites 1 and 4 respectively) and a poorly conserved half-site (half-sites 2
      and 3 respectively). The sequence binds co-operatively two dimers of the
      glucocorticoid receptor (GR) and mediates efficient glucocorticoid regulation of
      gene expression. Analysis of deletions of the cAspAT gene promoter and subcloning
      of GRE A upstream of the thymidine kinase promoter indicate that this sequence is
      responsive to glucocorticoids, but not to androgens. Electrophoretic mobility
      shift assays indicate that the GRE A unit does not bind the androgen receptor
      (AR). The modification of three nucleotides in the poorly conserved half-sites 2
      and 3, converting GRE A into two overlapping high-affinity GREs (ov-cGRE),
      resulted in co-operative binding of the AR. Furthermore, ov-cGRE efficiently
      mediated androgen regulation of the thymidine kinase promoter. A single base
      modification in half-site 2 or 3 in GRE A allowed the binding of the AR as one or
      two dimers respectively, and restored transcriptional activation by androgens
      only in the latter case. Thus the poor affinity of the AR for half-sites 2 and 3
      prevented its binding to GRE A, indicating that the overlapping GRE A sequence of
      the cAspAT gene promoter discriminates a glucocorticoid-mediated from an androgen
      mediated response.

PMID- 10926837
TI  - Kinetic and structural analysis of the ultrasensitive behaviour of cyanobacterial
      ADP-glucose pyrophosphorylase.
AB  - The kinetic and (supra)molecular properties of the ultrasensitive behaviour of
      ADP-glucose pyrophosphorylase (AGPase) from Anabaena PCC 7120 (a cyanobacterium)
      were exhaustively studied. The response of the enzyme toward the allosteric
      activator 3-phosphoglycerate (3PGA) occurs with ultrasensitivity as a consequence
      of the cross-talk with the inhibitor P(i). Molecular 'crowding' renders AGPase
      more sensitive to the interplay between the allosteric regulators and,
      consequently, enhances the ultrasensitive response. In crowded media, and when
      orthophosphate is present, the activation kinetics of the enzyme with 3PGA
      proceed with increased co-operativity and reduced affinity toward the activator.
      Under conditions of ultrasensitivity, the enzyme's maximal activation takes place
      in a narrow range of 3PGA concentrations. Moreover, saturation kinetics of the
      enzyme with respect to its substrates, glucose 1-phosphate and ATP, were
      different at low or high 3PGA levels in crowded media. Only under the latter
      conditions did AGPase exhibit discrimination between low or high levels of the
      activator, which increased the affinity toward the substrates and the maximal
      activity reached by the enzyme. Studies of fluorescence emission of tryptophan
      residues, fourth-derivative spectroscopy and size-exclusion chromatography
      indicated that the ultrasensitive behaviour is correlated with intramolecular
      conformational changes induced in the tertiary structure of the homotetrameric
      enzyme. The results suggest a physiological relevance of the ultrasensitive
      response of AGPase in vivo, since the enzyme could be subtly sensing changes in
      the levels of allosteric regulators and substrates, and thus determining the flux
      of metabolites toward synthesis of storage polysaccharides.

PMID- 10926838
TI  - Stimulation of fructose transport across the intestinal brush-border membrane by
      PMA is mediated by GLUT2 and dynamically regulated by protein kinase C.
AB  - Perfusion of rat jejunum in vitro with PMA increased fructose transport by 70%
      compared with control values and was blocked by the protein kinase C (PKC)
      inhibitor chelerythrine. The brush-border membrane contained both the fructose
      transporters GLUT5 and GLUT2; the presence of the latter was confirmed by luminal
      biotinylation. PMA increased the GLUT2 level 4-fold within minutes, so that the
      level was comparable with that of the basolateral membrane, but had no effect on
      GLUT5 level. GLUT2 was functional, accessible to luminal fructose and could be
      inhibited selectively by phloretin to permit determination of GLUT2- and GLUT5
      mediated transport components. The 4-fold increase in GLUT2 level induced by PMA
      was matched by a 4-fold increase in GLUT2-mediated transport: there was a
      compensatory fall in the GLUT5-mediated rate. The pattern of dynamic trafficking
      was seen only for GLUT2, not GLUT5 or SGLT1, implying that GLUT2 trafficks to the
      brush-border membrane by a different pathway. Trafficking of GLUT2 to the brush
      border membrane correlated with activation of PKC betaII, implying that this
      isoenzyme is likely to control trafficking. Since PKC is activated by endogenous
      hormones, GLUT2 levels in vivo are 3-4-fold those in vitro; moreover, because PKC
      is inactivated as soon as intestine is excised, GLUT2 is lost from the brush
      border within minutes in vitro. It is therefore difficult to detect GLUT2 in most
      in vitro preparations and its role in intestinal sugar absorption across the
      brush-border membrane has accordingly been overlooked.

PMID- 10926836
TI  - Tumour necrosis factor-alpha and interferon-gamma synergistically activate the
      RANTES promoter through nuclear factor kappaB and interferon regulatory factor 1
      (IRF-1) transcription factors.
AB  - Inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha) and
      interferon-gamma (IFN-gamma) synergistically activate expression of the RANTES
      (regulated upon activation, normal T-cell expressed and secreted) gene, which
      plays a crucial role in the chemoattraction of leukocytes during the inflammatory
      response. To understand at the molecular level the mechanism by which the two
      cytokines activate RANTES gene expression, we determined the requirement of cis
      acting elements in the RANTES promoter and trans-acting factors. The murine
      RANTES promoter contained one putative interferon regulatory factor, IRF, and
      three putative nuclear factor kappaB (NF-kappaB) binding sites. Specific
      destruction of the IRF binding site and one of the three NF-kappaB binding sites
      abolished the inducibility of promoter activity by IFN-gamma and TNF-alpha,
      respectively. In contrast, mutation of the other two putative NF-kappaB binding
      sites did not affect RANTES promoter activity significantly. In addition, the
      RANTES promoter was stimulated by co-transfection of plasmids that expressed
      either p65, an NF-kappaB family protein, or the IRF-1 transcription factor.
      RANTES promoters with mutations in the NF-kappaB or IRF binding sites were not
      stimulated by p65 or IRF-1 expression, respectively. In electrophoretic mobility
      shift and immunologic assays, we showed that IRF-1 was induced after cells were
      treated with IFN-gamma and that NF-kappaB was activated by TNF-alpha treatment.
      These results demonstrate that both NF-kappaB and IRF-1 transcription factors
      mediate the induction of RANTES expression via their cognate cis-acting elements
      when cells are stimulated by TNF-alpha and IFN-gamma.

PMID- 10926840
TI  - Regulation of GLUT5, GLUT2 and intestinal brush-border fructose absorption by the
      extracellular signal-regulated kinase, p38 mitogen-activated kinase and
      phosphatidylinositol 3-kinase intracellular signalling pathways: implications for
      adaptation to diabetes.
AB  - We have investigated the role of the extracellular signal-regulated kinase (ERK),
      p38 and phosphatidylinositol 3-kinase (PI 3-kinase) pathways in the regulation of
      intestinal fructose transport. Different combinations of anisomycin, PD98059 and
      wortmannin had very different effects on fructose transport in perfused isolated
      loops of rat jejunum. Transport was stimulated maximally by anisomycin (2 microM)
      and blocked by SB203580 (20 microM), confirming involvement of the p38 pathway.
      PD98059 (50 microM) alone had little effect on fructose transport. However, it
      had a dramatic effect on stimulation by anisomycin, diminishing the K(a) 50-fold
      from 1 microM to 20 nM to show that the ERK pathway restrains the p38 pathway.
      The K(a) for diabetic jejunum was 30 nM and PD98059 had no effect. Transport in
      the presence of anisomycin was 3.4-fold that for anisomycin plus PD98059 plus
      wortmannin. Transport was mediated by both GLUT5 and GLUT2. In general, GLUT2
      levels increased up to 4-fold within minutes and with only minimal changes in
      GLUT5 or SGLT1 levels, demonstrating that GLUT2 trafficks by a rapid trafficking
      pathway distinct from that of GLUT5 and SGLT1. GLUT2 intrinsic activity was
      regulated over a 9-fold range. It is concluded that there is extensive cross-talk
      between the ERK, p38 and PI 3-kinase pathways in their control of brush-border
      fructose transport by modulation of both the levels and intrinsic activities of
      GLUT5 and GLUT2. The potential of the intracellular signalling pathways to
      regulate short-term nutrient transport during the assimilation of a meal and
      longer-term adaptation to diabetes and hyperglycaemia is discussed.

PMID- 10926839
TI  - The diffusive component of intestinal glucose absorption is mediated by the
      glucose-induced recruitment of GLUT2 to the brush-border membrane.
AB  - We have investigated the mechanism responsible for the diffusive component of
      intestinal glucose absorption, the major route by which glucose is absorbed. In
      perfused rat jejunum in vivo, absorption was strongly inhibited by phloretin, an
      inhibitor of GLUT2. The GLUT2 level at the brush-border membrane increased some 2
      fold when the luminal glucose concentration was changed from 0 to 100 mM. The
      phloretin-sensitive or diffusive component of absorption appeared superficially
      linear and consistent with simple diffusion, but was in fact carrier-mediated and
      co-operative (n=1.6, [G(1/2)]=56 mM; where [G(1/2)] is the glucose concentration
      at half V(max)) because of the glucose-induced activation and recruitment of
      GLUT2 to the brush-border membrane. Diffusive transport by paracellular flow was
      negligible. The phloretin-insensitive, SGLT1-mediated, component of glucose
      absorption showed simple saturation kinetics with [G(1/2)]=27 mM: the activation
      of protein kinase C (PKC) betaII, the isoenzyme of PKC that most probably
      controls GLUT2 trafficking [Helliwell, Richardson, Affleck and Kellett (2000)
      Biochem. J. 350, 149-154], also showed simple saturation kinetics, with
      [G(1/2)]=21 mM. We conclude that the principal route for glucose absorption is by
      GLUT2-mediated facilitated diffusion across the brush-border membrane, which is
      up to 3-fold greater than that by SGLT1; the magnitude of the diffusive component
      at any given glucose concentration correlates with the SGLT1-dependent activation
      of PKC betaII. The implications of these findings for the assimilation of sugars
      immediately after a meal are discussed.

PMID- 10926842
TI  - Catabolism of aggrecan, decorin and biglycan in tendon.
AB  - We have examined the catabolism of the proteoglycans aggrecan, decorin and
      biglycan in fresh tendon samples and in explant cultures of tissue from the
      tensional and compressed regions of young and mature bovine tendons. A panel of
      well-characterized antibodies that recognize glycosaminoglycan or protein (linear
      or neoepitope) sequences was used to detect proteoglycans and proteoglycan
      degradation products that were both retained within the tissue and released into
      the culture medium. In addition, a reverse-transcriptase-mediated PCR analysis
      was used to examine the mRNA expression patterns of tendon proteoglycans and
      aggrecanases. The results of this study indicate a major role for aggrecanase(s)
      in the catabolism of aggrecan in bovine tendon. The study also provides a
      characterization of glycosaminoglycan epitopes associated with the proteoglycans
      of tendon, illustrating age-related changes in the isomers of chondroitin
      sulphate disaccharides that remain attached to the core protein glycosaminoglycan
      linkage region after digestion with chondroitinase ABC. Evidence for a rapid
      turnover of the small proteoglycans decorin and biglycan was also observed,
      indicating additional molecular pathways that might compromise the integrity of
      the collagen matrix and potentially contribute to tendon dysfunction after injury
      and during disease.

PMID- 10926841
TI  - Substrates of semicarbazide-sensitive amine oxidase co-operate with vanadate to
      stimulate tyrosine phosphorylation of insulin-receptor-substrate proteins,
      phosphoinositide 3-kinase activity and GLUT4 translocation in adipose cells.
AB  - It has been shown that the combination of benzylamine or tyramine and low
      concentrations of vanadate markedly stimulates glucose transport in rat
      adipocytes by a mechanism that requires semicarbazide-sensitive amine oxidase
      (SSAO) activity and H(2)O(2) formation. Here we have further analysed the insulin
      like effects of the combination of SSAO substrates and vanadate and we have
      studied the signal-transduction pathway activated in rat adipocytes. We found
      that several SSAO substrates (benzylamine, tyramine, methylamine, n-decylamine,
      histamine, tryptamine or beta-phenylethylamine), in combination with low
      concentrations of vanadate, stimulate glucose transport in isolated rat
      adipocytes. Furthermore, SSAO substrates together with vanadate stimulated the
      recruitment of GLUT4 to the cell surface in isolated rat adipocytes. Benzylamine
      plus vanadate also stimulated glucose transport and GLUT4 translocation in 3T3-L1
      adipocytes. Benzylamine or tyramine in combination with vanadate potently
      stimulated the tyrosine phosphorylation of both insulin receptor substrate (IRS)
      1 and IRS-3. In contrast, benzylamine and vanadate caused only a weak stimulation
      of insulin receptor kinase. Benzylamine or tyramine in combination with vanadate
      also stimulated phosphoinositide 3-kinase activity; wortmannin abolished the
      stimulatory effect of benzylamine and vanadate on glucose transport in adipose
      cells. Furthermore, the administration of benzylamine and vanadate in vivo caused
      a rapid lowering of plasma glucose levels, which took place in the absence of
      alterations in plasma insulin. On the basis of these results we propose that SSAO
      activity regulates glucose transport in adipocytes. SSAO oxidative activity
      stimulates glucose transport via the translocation of GLUT4 carriers to the cell
      surface, resulting from a potent tyrosine phosphorylation of IRS-1 and IRS-3 and
      phosphoinositide 3-kinase activation. Our results also indicate that substrates
      of SSAO might regulate glucose disposal in vivo.

PMID- 10926843
TI  - Identification of domains responsible for signal recognition and transduction
      within the QUTR transcription repressor protein.
AB  - QUTR (qutR-encoded transcription-repressing protein) is a multi-domain repressor
      protein active in the signal-transduction pathway that regulates transcription of
      the quinic acid utilization (qut) gene cluster in Aspergillus nidulans. In the
      presence of quinate, production of mRNA from the eight genes of the qut pathway
      is stimulated by the activator protein QUTA (qutA-encoded transcription
      activating protein). Mutations in the qutR gene alter QUTR function such that the
      transcription of the qut gene cluster is permanently on (constitutive phenotype)
      or is insensitive to the presence of quinate (super-repressed phenotype). These
      mutant phenotypes imply that the QUTR protein plays a key role in signal
      recognition and transduction, and we have used deletion analysis to determine
      which regions of the QUTR protein are involved in these functions. We show that
      the QUTR protein recognizes and binds to the QUTA protein in vitro and that the N
      terminal 88 amino acids of QUTR are sufficient to inactivate QUTA function in
      vivo. Deletion analysis and domain-swap experiments imply that the two C-terminal
      domains of QUTR are mainly involved in signal recognition.

PMID- 10926844
TI  - Cloning and characterization of a novel human histone deacetylase, HDAC8.
AB  - Histone deacetylases (HDACs) are a growing family of enzymes implicated in
      transcriptional regulation by affecting the acetylation state of core histones in
      the nucleus of cells. HDACs are known to have key roles in the regulation of cell
      proliferation [Brehm, Miska, McCance, Reid, Bannister and Kouzarides (1998)
      Nature (London) 391, 597-600], and aberrant recruitment of an HDAC complex has
      been shown to be a key step in the mechanism of cell transformation in acute
      promyelocytic leukaemia [Grignani, De Matteis, Nervi, Tomassoni, Gelmetti, Cioce,
      Fanelli, Ruthardt, Ferrara, Zamir et al. (1998) Nature (London) 391, 815-818;
      Lin, Nagy, Inoue, Shao, Miller and Evans (1998), Nature (London) 391, 811-814].
      Here we present the complete nucleotide sequence of a cDNA clone, termed HDAC8,
      that encodes a protein product with similarity to the RPD3 class (I) of HDACs.
      The predicted 377-residue HDAC8 product contains a shorter C-terminal extension
      relative to other members of its class. After expression in two cell systems,
      immunopurified HDAC8 is shown to possess trichostatin A- and sodium butyrate
      inhibitable HDAC activity on histone H4 peptide substrates as well as on core
      histones. Expression profiling reveals the expression of HDAC8 to various degrees
      in every tissue tested and also in several tumour lines. Mutation of two adjacent
      histidine residues within the predicted active site severely decreases activity,
      confirming these residues as important for HDAC8 enzyme activity. Finally,
      linkage analysis after radiation hybrid mapping has localized HDAC8 to
      chromosomal position Xq21.2-Xq21.3. These results confirm HDAC8 as a new member
      of the HDAC family.

PMID- 10926845
TI  - Phosphoinositide 3-kinase-dependent Ras activation by tauroursodesoxycholate in
      rat liver.
AB  - Ursodesoxycholic acid, widely used for the treatment of cholestatic liver
      disease, causes choleretic, anti-apoptotic and immunomodulatory effects. Here the
      effects on choleresis of its taurine conjugate tauroursodesoxycholate (TUDC),
      which is present in the enterohepatic circulation, were correlated with the
      activation of important elements of intracellular signal transduction in cultured
      rat hepatocytes and perfused rat liver. TUDC induced a time- and concentration
      dependent activation of the small GTP-binding protein Ras and of phosphoinositide
      3-kinase (PI 3-kinase) in cultured hepatocytes. Ras activation was dependent on
      PI 3-kinase activity, without the involvement of protein kinase C- and genistein
      sensitive tyrosine kinases. Ras activation by TUDC was followed by an activation
      of the mitogen-activated protein kinases extracellular-signal-regulated kinase-1
      (Erk-1) and Erk-2. In perfused rat liver, PI 3-kinase inhibitors largely
      abolished the stimulatory effect of TUDC on taurocholate excretion, suggesting an
      important role for a PI 3-kinase/Ras/Erk pathway in the choleretic effect of
      TUDC.

PMID- 10926846
TI  - Peroxidation of proteins before lipids in U937 cells exposed to peroxyl radicals.
AB  - This study provides the first report of the formation of protein hydroperoxides
      in cells attacked by reactive oxygen species. U937 cells exposed to peroxyl
      radicals generated by the thermal decomposition of a water-soluble azo compound
      gradually accumulated hydroperoxide (-OOH) groups. In an incubation for 22 h, 1.2
      mM peroxyl radicals was generated and each cell acquired 1.5x10(8) -OOH groups.
      These groups were located on the cell proteins; no lipid peroxidation was
      detected. The extent of protein peroxidation was proportional to the rate of
      generation of the peroxyl radicals. There was no lag period before the onset of
      peroxidation, indicating that cell antioxidants could not protect the proteins.
      The half-life of protein hydroperoxides in cell suspensions was approx. 4 h at 37
      degrees C. Our results suggest that protein hydroperoxides might have a
      significant role as intermediates in the development of biological damage
      initiated by reactive oxygen species.

PMID- 10926847
TI  - The low-affinity monocarboxylate transporter MCT4 is adapted to the export of
      lactate in highly glycolytic cells.
AB  - Transport of lactate and other monocarboxylates in mammalian cells is mediated by
      a family of transporters, designated monocarboxylate transporters (MCTs). The
      MCT4 member of this family has recently been identified as the major isoform of
      white muscle cells, mediating lactate efflux out of glycolytically active
      myocytes [Wilson, Jackson, Heddle, Price, Pilegaard, Juel, Bonen, Montgomery,
      Hutter and Halestrap (1998) J. Biol. Chem. 273, 15920-15926]. To analyse the
      functional properties of this transporter, rat MCT4 was expressed in Xenopus
      laevis oocytes and transport activity was monitored by flux measurements with
      radioactive tracers and by changes of the cytosolic pH using pH-sensitive
      microelectrodes. Similar to other members of this family, monocarboxylate
      transport via MCT4 is accompanied by the transport of H(+) across the plasma
      membrane. Uptake of lactate strongly increased with decreasing extracellular pH,
      which resulted from a concomitant drop in the K(m) value. MCT4 could be
      distinguished from the other isoforms mainly in two respects. First, MCT4 is a
      low-affinity MCT: for L-lactate K(m) values of 17+/-3 mM (pH-electrode) and 34+/
      5 mM (flux measurements with L-[U-(14)C]lactate) were determined. Secondly,
      lactate is the preferred substrate of MCT4. K(m) values of other monocarboxylates
      were either similar to the K(m) value for lactate (pyruvate, 2-oxoisohexanoate, 2
      oxoisopentanoate, acetoacetate) or displayed much lower affinity for the
      transporter (beta-hydroxybutyrate and short-chain fatty acids). Under
      physiological conditions, rat MCT will therefore preferentially transport
      lactate. Monocarboxylate transport via MCT4 could be competitively inhibited by
      alpha-cyano-4-hydroxycinnamate, phloretin and partly by 4, 4'-di
      isothiocyanostilbene-2,2'-disulphonic acid. Similar to MCT1, monocarboxylate
      transport via MCT4 was sensitive to inhibition by the thiol reagent p
      chloromercuribenzoesulphonic acid.

PMID- 10926848
TI  - Identification of amino acid residues important in the cyclization reactions of
      chalcone and stilbene synthases.
AB  - Chalcone synthase (CHS) and stilbene synthase (STS) catalyse condensation
      reactions of p-coumaroyl-CoA and three C(2) units from malonyl-CoA up to a common
      tetraketide intermediate but then catalyse different cyclization reactions to
      produce naringenin chalcone and resveratrol respectively. On the basis of
      sequence alignment with other condensing enzymes including 3-ketoacyl-(acyl
      carrier protein) synthases of polyketide and fatty-acid synthases, site-directed
      mutagenesis was performed on the active-site G(372)FGPG loops in CHS and STS. The
      CHS-P375G mutant showed a 6-fold decrease in overall condensing activity with
      selectively increased production of p-coumaroyltriacetic acid lactone (CTAL, the
      derailment product of the tetraketide intermediate). Meanwhile, resveratrol
      production by STS-P(375)G strongly decreased to give various products in the
      order CTAL> resveratrol approximately bisnoryangonin>naringenin. As a result,
      naringenin production (cross-reaction) by STS-P(375)G was close to 30% of
      resveratrol production. Both G(374)L mutants of CHS and STS showed no condensing
      activity with residual malonyl-CoA decarboxylase activity. These results
      suggested that the G(372)FGPG loop in CHS and STS contribute to a determination
      of the outcome during cyclization reactions by serving as a part of the active
      site scaffold on which the stereochemistry of cyclization is performed. These
      observations provide the first biochemical indication that cyclization reactions
      are modulated by active-site geometry. The implications for the evolutionary
      relationship of these enzymes are also discussed.

PMID- 10926849
TI  - Kinetics of a self-amplifying substrate cycle: ADP-ATP cycling assay.
AB  - A kinetic study of an ATP-ADP amplification cyclic system involving the enzymes
      adenylate kinase, pyruvate kinase and L-lactate dehydrogenase has been made. The
      stoichiometry of the cycle is 2:1, because two molecules of ADP are synthesized
      from one each of ATP and AMP, and one molecule of ADP is converted back into one
      of ATP at each turn of the cycle. This results in a continuous exponential
      increase in the concentrations of ATP and ADP in the reaction medium, according
      to the equations obtained. This is therefore a substrate cycle that amplifies
      itself, the cycling rate increasing continuously with time. The background signal
      of the reagent was reduced by using apyrase to degrade ATP and ADP in the
      reagent, permitting detection limits as low as 16 pmol of ATP and/or ADP in a
      continuous spectrophotometric assay.

PMID- 10926850
TI  - Effect of heparin and liver heparan sulphate on interaction of HepG2-derived
      transcription factors and their cis-acting elements: altered potential of
      hepatocellular carcinoma heparan sulphate.
AB  - Proteoglycan assembly in malignant tumours is subject to profound changes. The
      significance of these alterations is not well understood; especially, their role
      in nuclear regulation is a topic for debate. The capacity of heparin and liver
      carcinoma heparan sulphate (HS) to alter DNA-transcription factor interactions
      has been studied to provide further evidence concerning the regulatory potential
      of glycosaminoglycan (GAG) in the nucleus. Experiments both in vitro and in vivo
      indicated that heparin and HS are capable of inhibiting the interaction of
      transcription factors with their consensus oligonucleotide elements. Among five
      transcription factors studied, AP-1, SP-1, ETS-1 and nuclear factor kappaB proved
      to be sensitive to heparin and heparan sulphate, whereas TFIID was hardly
      inhibited in either in vitro or in vivo systems. Interestingly, HS from
      peritumoral liver was five times more effective than heparin. Liver carcinoma HS
      was less effective than liver HS, but its activity was comparable with that of
      heparin. These results indicate that the structural differences of GAG chains
      strongly influence their biological behaviour. The loss of their recognized
      functional activity in malignant tumours might promote the development of
      uncontrolled growth and gene expression favouring the neoplastic process.

PMID- 10926851
TI  - Structural basis for the functional difference between Smad2 and Smad3 in FAST-2
      (forkhead activin signal transducer-2)-mediated transcription.
AB  - Smad2 and Smad3 are signalling proteins that are involved in mediating the
      transcriptional regulation of target genes downstream of transforming growth
      factor-beta and activin receptors. Although they are structurally very similar,
      Smad2 and Smad3 have some functional differences in transducing signals for these
      receptors. In FAST-2 (forkhead activin signal transducer-2)-mediated
      transcriptional regulation using the activin-responsive element derived from
      Xenopus Mix.2 promoter as a reporter, Smad3 but not Smad2 alone was able to
      stimulate the transcription. In addition, Smad3 was able to inhibit the
      transactivation of the promoter induced by co-expression of Smad2, Smad4 and an
      active activin type-I receptor. We used a series of chimaeras between Smad1 and
      Smad3 and found that the Mad homology 1 (MH1) domain of Smad3 was indispensable
      for the dual regulatory function of Smad3. However, this Smad3-specific function
      could not be manifested in Smad2 mutants that were devoid of the two amino acid
      insertions (at the MH1 domain) that comprise the major structural difference
      between Smad2 and Smad3, indicating that other structural motifs are involved in
      determining the regulatory activity of Smad3. By using chimaeras between Smad2
      and Smad3, we found that the most N-terminal portion of Smad3 was crucial for its
      function. Taken together, these results suggest that, as compared with Smad2, the
      unique function of Smad3 in modulating the FAST-2-mediated transcription is
      contributed to by a subtle difference in the structural features at the MH1
      domain.

PMID- 10926852
TI  - Expression of escherichia coli otsA in a Saccharomyces cerevisiae tps1 mutant
      restores trehalose 6-phosphate levels and partly restores growth and fermentation
      with glucose and control of glucose influx into glycolysis.
AB  - The TPS1 gene, encoding trehalose-6-phosphate synthase (TPS), exerts an essential
      control on the influx of glucose into glycolysis in the yeast Saccharomyces
      cerevisiae. The deletion of TPS1 causes an inability to grow on glucose because
      of a hyperaccumulation of sugar phosphates and depletion of ATP and phosphate. We
      show that expression of the Escherichia coli homologue, otsA, in a yeast tps1
      mutant results in high TPS activity. Although the trehalose 6-phosphate (Tre6P)
      level during exponential growth on glucose was at least as high as in a wild-type
      yeast strain, growth on glucose was only partly restored and the lag phase was
      much longer. Measurement of the glycolytic metabolites immediately after the
      addition of glucose showed that in spite of a normal Tre6P accumulation there was
      still a partial hyperaccumulation of sugar phosphates. Strong elevation of the
      Tre6P level by the additional deletion of the TPS2 gene, which encodes Tre6P
      phosphatase, was not able to cause a strong decrease in the sugar phosphate
      levels in comparison with the wild-type strain. In addition, in chemostat
      experiments the short-term response to a glucose pulse was delayed, but normal
      metabolism was regained over a longer period. These results show that Tre6P
      synthesis from a heterologous TPS enzyme can to some extent restore the control
      of glucose influx into glycolysis and growth on glucose in yeast. However, they
      also indicate that the yeast TPS enzyme, as opposed to the E. coli otsA gene
      product, is able to increase the efficiency of the Tre6P control on glucose
      influx into yeast glycolysis.

PMID- 10926853
TI  - Fine mapping of the alpha-actinin binding site within cysteine-rich protein.
AB  - The cysteine-rich proteins (CRPs) are a family of highly conserved LIM (an
      acronym derived from the three gene products lin-11, isl-1 and mec-3) domain
      proteins that have been implicated in muscle differentiation. All CRP family
      members characterized so far have been shown to interact with the filamentous
      actin cross-linker alpha-actinin. The region of CRP required for this interaction
      has previously been broadly mapped to the molecule's N-terminal half. Here we
      report that the alpha-actinin-binding region of CRP, which we have mapped by
      using a combination of blot overlay and Western immunoblot techniques, is
      confined to an 18-residue sequence occurring within the protein's N-terminal
      glycine-rich repeat. A site-directed mutagenesis analysis of the binding region
      has revealed the critical importance of a single lysine residue (lysine 65 in
      human CRP1). Alterations at this site lead to a 10-fold decrease in alpha-actinin
      binding in comparison with wild-type CRP. The critical lysine residue localizes
      within a short alpha-helix, raising the possibility that mutagenesis-induced
      alterations in alpha-actinin-binding capacity might be attributed to the
      disruption of a key structural element.

PMID- 10926854
TI  - Membrane pore architecture of a cytolytic toxin from Bacillus thuringiensis.
AB  - To investigate the membrane pore structure of Cyt2Aa1 toxin from Bacillus
      thuringiensis, 14 single-cysteine substitutions of the toxin were constructed.
      Five of these mutants (L172C, V186C, L189C, E214C and L220C) yielded
      characteristic products when processed by proteinase K; other mutants were
      degraded by this enzyme. Mutants that yielded characteristic proteolysed products
      and wild-type toxin were labelled with polarity-sensitive acrylodan (6-acryloyl-2
      dimethylaminonaphthalene) at the thiol group of cysteine residues. A green-blue
      shift in the emission spectra was observed with all labelled toxins on transfer
      from an aqueous solution into a solution containing membranes or liposomes from
      red blood cells. These results suggested that the label moved into the
      hydrophobic environment of the membrane or became buried within hydrophobic
      regions of the protein oligomers. Digestion of membrane-bound labelled toxin with
      proteinase K did not cause a significant decrease in emission intensity from any
      of the labelled mutants. This suggests that L172C, V186C, L189C, E214C and L220C
      are inserted into the membrane and are therefore protected from proteolysis. In
      contrast, a marked decrease in emission intensity was observed when membrane
      bound labelled wild-type toxin was digested with proteinase K. This suggests that
      Cys-19 does not insert into the membrane. Fluorimetric analysis of delipidated
      pore complexes suggests that L172C, V186C, L189C and E214C point towards the
      lipid in the membrane, whereas L220C is either within the hydrophobic environment
      of the protein oligomers or exposed to the membrane lipids. Most of the Cys-19
      from wild-type molecules is enclosed within the hydrophobic pockets of the
      protein oligomers.

PMID- 10926856
TI  - Thrombospondin 1 does not activate transforming growth factor beta1 in a
      chemically defined system or in smooth-muscle-cell cultures.
AB  - The cytokine transforming growth factor beta1 (TGF-beta1) is secreted in a latent
      form that has no known biological activity. The conversion of latent TGF-beta1
      into its biologically active 25 kDa form is thought to be an important step in
      the regulation of TGF-beta activity both in cell culture and in vivo.
      Thrombospondin (TSP)-1, a 360 kDa platelet alpha-granule and extracellular matrix
      protein, has been shown to participate in TGF-beta1 activation. We have used a
      chemically defined system to examine the mechanism of TSP-1-mediated TGF-beta1
      activation. However, the addition of two different preparations of TSP-1 to
      recombinant small latent TGF-beta1 in the test tube resulted in only a very small
      increase in the proportion of the TGF-beta1 able to bind to the TGF-beta type II
      receptor: from 0.1% to a maximum of 0.4%. This small effect was not specific for
      TSP-1: matrix metalloproteinase 2, tissue inhibitor of matrix metalloproteinase 2
      and active plasminogen activator inhibitor 1, but not transglutaminase, human
      serum albumin or immunoglobulin, had quantitatively similar effects on latent TGF
      beta1. Furthermore, no change in the activity associated with small latent TGF
      beta1 was noted in either mink lung epithelial cell or rat aortic smooth-muscle
      cell culture systems in the presence of TSP-1 (or TSP-1-derived peptides). We
      conclude that TSP-1, either alone or in the presence of cultured smooth-muscle
      cells (a cell type known to activate latent TGF-beta in vitro and in vivo) is
      unable to activate latent TGF-beta1. Any TSP-mediated activation of TGF-beta1
      must depend on additional factor(s) not present in our systems.

PMID- 10926855
TI  - Interaction of the collagen-like tail of asymmetric acetylcholinesterase with
      heparin depends on triple-helical conformation, sequence and stability.
AB  - The collagen-like tail of asymmetric acetylcholinesterase (AChE) contains two
      heparin-binding domains (HBDs) that interact with heparan sulphate proteoglycans,
      determining the anchoring of the enzyme at the basal lamina and its specific
      localization at the neuromuscular junction. Both HBDs are characterized by a
      cluster of basic residues containing a core with the BBXB consensus sequence
      (where B represents a basic residue and X a non-basic residue). To study the
      interaction of such HBDs with heparin we have used synthetic peptides to model
      the N-terminal and C-terminal sites. CD spectroscopy showed that all peptides are
      triple-helical at low temperatures, and undergo trimer-to-monomer transitions.
      Displacement assays of asymmetric AChE bound to heparin were performed using the
      peptides in both monomeric and triple-helical states. In the monomeric
      conformation, all the peptides were able to displace low levels of AChE depending
      on the basic charge content. In the triple-helical conformation, peptides
      containing the consensus sequence showed a large increase in the ability to
      displace bound AChE. Results suggest that the specific binding of the collagen
      like-tail peptides to heparin depends both on the presence of the core sequence
      and on the triple-helical conformation. Moreover, BBXB-containing peptides that
      are less stable are more effective in displacing AChE, suggesting that the
      interaction region needs a significant amount of structural flexibility to better
      accommodate the ligand.

PMID- 10926857
TI  - Differential regulation of Ca2+/calmodulin-dependent enzymes by plant calmodulin
      isoforms and free Ca2+ concentration.
AB  - Multiple calmodulin (CaM) isoforms are expressed in plants, but their biochemical
      characteristics are not well resolved. Here we show the differential regulation
      exhibited by two soya bean CaM isoforms (SCaM-1 and SCaM-4) for the activation of
      five CaM-dependent enzymes, and the Ca(2+) dependence of their target enzyme
      activation. SCaM-1 activated myosin light-chain kinase as effectively as brain
      CaM (K(act) 1.8 and 1.7 nM respectively), but SCaM-4 produced no activation of
      this enzyme. Both CaM isoforms supported near maximal activation of CaM-dependent
      protein kinase II (CaM KII), but SCaM-4 exhibited approx.12-fold higher K(act)
      than SCaM-1 for CaM KII phosphorylation of caldesmon. The SCaM isoforms showed
      differential activation of plant and animal Ca(2+)-ATPases. The plant Ca(2+)
      ATPase was activated maximally by both isoforms, while the erythrocyte Ca(2+)
      ATPase was activated only by SCaM-1. Plant glutamate decarboxylase was activated
      fully by SCaM-1, but SCaM-4 exhibited an approx. 4-fold increase in K(act) and an
      approx. 25% reduction in V(max). Importantly, SCaM isoforms showed a distinct
      Ca(2+) concentration requirement for target enzyme activation. SCaM-4 required 4
      fold higher [Ca(2+)] for half-maximal activation of CaM KII, and 1.5-fold higher
      [Ca(2+)] for activation of cyclic nucleotide phosphodiesterase than SCaM-1. Thus
      these plant CaM isoforms provide a mechanism by which a different subset of
      target enzymes could be activated or inhibited by the differential expression of
      these CaM isoforms or by differences in Ca(2+) transients.

PMID- 10926859
TI  - Oxygen and haem regulate the synthesis of peroxisomal proteins: catalase A, acyl
      CoA oxidase and Pex1p in the yeast Saccharomyces cerevisiae; the regulation of
      these proteins by oxygen is not mediated by haem.
AB  - Saccharomyces cerevisiae genes related to respiration are typically controlled by
      oxygen and haem. Usually the regulation by these factors is co-ordinated; haem is
      indicated as the oxygen sensor. However, the responsiveness of peroxisome
      functions to these regulatory factors is poorly understood. The expression of
      CTA1, POX1 and PEX1 genes encoding the peroxisomal proteins catalase A, acyl-CoA
      oxidase and Pex1p peroxin respectively was studied under various conditions: in
      anaerobiosis, in the absence of haem and in respiratory incompetence caused by
      the lack of a mitochondrial genome (rho(0)). The influence of haem deficiency or
      rho(0) on peroxisomal morphology was also investigated. Respiratory incompetence
      has no effect on the expression of CTA1 and POX1, whereas in the absence of haem
      their expression is markedly decreased. The synthesis of Pex1p is decreased in
      rho(0) cells and is decreased even more in haem-deficient cells. Nevertheless,
      peroxisomal morphology in both these types of cell does not differ significantly
      from the morphology of peroxisomes in wild-type cells. The down-regulating effect
      of anoxia on the expression of CTA1 and POX1 is even stronger than the effect of
      haem deficiency and is not reversed by the addition of exogenous haem or the
      presence of endogenous haem. Moreover, neither of these genes responds to the
      known haem-controlled transcriptional factor Hap1p. In contrast with the other
      two genes studied, PEX1 is up-regulated in anaerobiosis. The existence of one or
      more novel mechanisms of regulation of peroxisomal genes by haem and oxygen,
      different from those already known in S. cerevisiae, is postulated.

PMID- 10926858
TI  - Interleukin 1 induces hypoxia-inducible factor 1 in human gingival and synovial
      fibroblasts.
AB  - Rheumatoid arthritis and periodontitis are inflammatory diseases modulated by
      proinflammatory cytokines [e.g. interleukin (IL-1) 1 and tumour necrosis factor
      alpha], which activate local fibroblasts to do the following: (1) proliferate,
      (2) induce gene expression and (3) produce destructive metalloproteinases.
      Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor
      (composed of HIF-1alpha and HIF-1beta/aryl hydrocarbon receptor nuclear
      transporter) that is modulated by hypoxia. HIF-1 binds to and induces several
      genes containing an HIF-1 consensus-binding site, including vascular endothelial
      growth factor and several glycolytic enzymes. Through differential screening of a
      human synovial fibroblast cDNA library, we identified HIF-1alpha as a clone up
      regulated by IL-1. The mRNA for HIF-1alpha subunit was increased 3-4-fold by
      Northern blot analysis after cells had been incubated for 3 h in the presence of
      IL-1. In addition, IL-1 increased the binding of the heterodimer HIF-1 to the HIF
      consensus sequence. These results suggest that HIF-1 might have a role in
      inflammation, possibly in attempting to re-establish homoeostasis.

PMID- 10926860
TI  - Purification and characterization of Ak.1 protease, a thermostable subtilisin
      with a disulphide bond in the substrate-binding cleft.
AB  - Ak.1 protease, a thermostable subtilisin isolated originally from Bacillus st.
      Ak.1, was purified to homogeneity from the Escherichia coli clone PB5517. It is
      active against substrates containing neutral or hydrophobic branched-chain amino
      acids at the P(1) site, such as valine, alanine or phenylalanine. The K(m) and
      k(cat) of the enzyme decrease with decreasing temperature, though not to the same
      degree with all substrates, suggesting that specificity changes with temperature.
      The protease is markedly stabilized by Ca(2+) ions. At 70 degrees C, a 10-fold
      increase in Ca(2+) concentration increases the half-life by three orders of
      magnitude. Ak.1 protease is stabilized by Ca(2+) to a greater extent than is
      thermitase. This may be due, in part, to the presence of an extra Ca(2+)-binding
      site in Ak.1 protease. Other metal ions, such as Sr(2+), increase the
      thermostability of the enzyme, but to a significantly lower degree than does
      Ca(2+). The structure of the protease showed the presence of a disulphide bond
      located within the active-site cleft. This bond influences both enzyme activity
      and thermostability. The disulphide bond appears to have a dual role: maintaining
      the integrity of the substrate-binding cleft and increasing the thermostability
      of the protease. The protease was originally investigated to determine its
      usefulness in the clean-up of DNA at high temperatures. However, it was found
      that this protease has a limited substrate specificity, so this application was
      not explored further.

PMID- 10926862
TI  - Call for papers : circulation research reports

PMID- 10926861
TI  - The analysis of intermolecular interactions in concentrated hyaluronan solutions
      suggest no evidence for chain-chain association.
AB  - Confocal fluorescence recovery after photobleaching (confocal-FRAP) was used to
      examine the influence of electrolytes (NaCl, KCl, MgCl(2), MnCl(2) and CaCl(2))
      on the network and hydrodynamic properties of fluoresceinamine-labelled
      hyaluronan (FA-HA) at concentrations up to 10 mg/ml. Self and tracer lateral
      diffusion coefficients showed that in Ca(2+) and Mn(2+), FA-HA (830 kDa) was more
      compact than in Mg(2+), Na(+) or K(+). These results were correlated with changes
      in the hydrodynamic radius of HA, determined by multi-angle laser-light
      scattering analysis in dilute solution, which was smaller in CaCl(2) (36 nm) than
      in NaCl (43 nm). The permeability of more concentrated solutions of HA (<10
      mg/ml) to FITC-dextran tracers (2000 kDa) was higher in CaCl(2). The properties
      of HA in urea (up to 6 M) were investigated to test for hydrophobic interactions
      and also in ethanol/water (up to 62%, v/v). In both, there was reduced
      hydrodynamic size and increased permeability to FITC-dextran, suggesting
      increased chain flexibility, but it did not show the changes predicted if chain
      chain association was disrupted by urea, or enhanced by ethanol. Oligosaccharides
      of HA (HA(20-26)) also had no effect on the self diffusion of high-molecular-mass
      FA-HA (830 kDa) solutions, or on dextran tracer diffusion, showing that there
      were no chain-chain interactions open to competition by short-chain segments. The
      results suggest that the effects of electrolytes and solvent are determined
      primarily by their effect on HA chain flexibility, with no evidence for
      association between chain segments contributing significantly to the major
      properties.

PMID- 10926863
TI  - Physiological effects of peroxynitrite: potential products of the environment.

PMID- 10926864
TI  - Myosin light chain phosphatase: a Cinderella of cellular signaling.

PMID- 10926865
TI  - Fibroblast growth factor-1 stimulates branching and survival of myocardial
      arteries: a goal for therapeutic angiogenesis?

PMID- 10926866
TI  - Oxidant signaling in vascular cell growth, death, and survival : a review of the
      roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic
      and apoptotic signaling.
AB  - Reactive oxygen species (ROS) have been traditionally regarded as toxic
      byproducts of aerobic metabolism. However, ROS can also act as intracellular
      signaling molecules in vascular cells. ROS can mediate phenotypes in vascular
      endothelial and smooth muscle cells that may be considered both physiological and
      pathophysiological. Among these are growth, apoptosis, and survival. The specific
      response elicited by reactive oxygen intermediaries is determined by their
      specific intracellular target(s). This, in turn, is dependent on the species of
      oxidant(s) produced, the source and therefore subcellular localization of the
      oxidant(s), the kinetics of production, and the quantities produced. A fuller
      understanding of how ROS regulate mitogenesis and apoptosis in vascular smooth
      muscle and endothelial cells will permit the development of novel strategies to
      modify or prevent vascular diseases in which these phenotypes predominate.

PMID- 10926867
TI  - Vascular cell apoptosis in remodeling, restenosis, and plaque rupture.

PMID- 10926868
TI  - Opioid peptide gene expression primes cardiogenesis in embryonal pluripotent stem
      cells.
AB  - Zinc finger-containing transcription factor GATA-4 and homeodomain Nkx-2.5 govern
      crucial developmental fates and have been found to promote cardiogenesis in
      embryonic cells exposed to the differentiating agent DMSO. Nevertheless,
      intracellular activators of these transcription factors are largely unknown. In
      this study, pluripotent P19 cells expressed the prodynorphin gene, an opioid gene
      encoding for the dynorphin family of opioid peptides. P19 cells were also able to
      synthesize and secrete dynorphin B, a biologically active end product of the
      prodynorphin gene. DMSO-primed GATA-4 and Nkx-2.5 gene expression was preceded by
      a marked increase in prodynorphin gene expression and dynorphin B synthesis and
      secretion. The DMSO effect occurred at the transcriptional level. In the absence
      of DMSO, dynorphin B triggered GATA-4 and Nkx-2.5 gene expression and led to the
      appearance of both alpha-myosin heavy chain and myosin light chain-2V
      transcripts, two markers of cardiac differentiation. Moreover, dynorphin B
      exposed cells were positively stained in the presence of MF 20, a mouse
      monoclonal antibody raised against the alpha-myosin heavy chain. Opioid receptor
      antagonism and inhibition of opioid gene expression by a prodynorphin antisense
      phosphorothioate oligonucleotide blocked DMSO-induced cardiogenesis, suggesting
      an autocrine role of an opioid gene in developmental decisions.

PMID- 10926869
TI  - Involvement of Rho-kinase-mediated phosphorylation of myosin light chain in
      enhancement of cerebral vasospasm.
AB  - Subarachnoid hemorrhage (SAH) often induces a long-term narrowing of the cerebral
      artery called cerebral vasospasm. Myosin light chain (MLC) in the spastic basilar
      artery was reported previously to be phosphorylated by Ca(2+)/calmodulin
      dependent MLC kinase. Because Rho-kinase, which is activated by the small GTPase
      Rho, phosphorylates not only MLC but also myosin phosphatase at its myosin
      binding subunit (MBS), thus inactivating myosin phosphatase, we examined whether
      Rho-kinase is involved in the development of vasospasm. Cerebral vasospasm was
      produced in the canine basilar artery by a 2-hemorrhage method, and
      vasocontractions were induced by topical application of 80 mmol/L KCl or 0.5
      micromol/L serotonin to the canine basilar artery exposed transclivally. The
      phosphorylation of MLC in the basilar artery was increased concurrently with an
      enhancement in the intensity of vasospasm with the passage of time after SAH. In
      addition, Rho-kinase in the basilar artery was activated concurrently with an
      increase in the phosphorylation of MBS at Ser854 in vasospasm. The Rho-kinase
      activation levels in vasospasm on days 0 and 2 were comparable to those in KCl-
      and serotonin-induced sustained vasocontraction, respectively, and those in
      vasospasm on day 7 were markedly high. The topical application of Y-27632, a
      specific inhibitor of Rho-kinase, to the exposed spastic basilar artery on day 7
      induced a dose-dependent dilation, and the intensities of vasospasm and the
      phosphorylation of MBS and MLC were simultaneously decreased by 10 micromol/L Y
      27632, although the decrease in MBS phosphorylation was more marked than the
      decrease in MLC phosphorylation. These results indicate that the activation of
      Rho-kinase and the phosphorylation of MLC and MBS occur concomitantly during
      vasospasm induced by SAH and suggest that Rho-kinase is involved in the
      enhancement of cerebral vasospasm in addition to Ca(2+)/calmodulin-dependent MLC
      kinase by increasing the phosphorylation of MLC directly or indirectly as a
      result of the inhibition of myosin phosphatase by its phosphorylation.

PMID- 10926870
TI  - Evidence for Ca(2+) activation and inactivation sites on the luminal side of the
      cardiac ryanodine receptor complex.
AB  - We have used tryptic digestion to determine whether Ca(2+) can regulate cardiac
      ryanodine receptor (RyR) channel gating from within the lumen of the sarcoplasmic
      reticulum (SR) or whether Ca(2+) must first flow through the channel and act via
      cytosolically located binding sites. Cardiac RyRs were incorporated into
      bilayers, and trypsin was applied to the luminal side of the bilayer. We found
      that before exposure to luminal trypsin, the open probability of RyR was
      increased by raising the luminal [Ca(2+)] from 10 micromol/L to 1 mmol/L, whereas
      after luminal trypsin exposure, increasing the luminal [Ca(2+)] reduced the open
      probability. The modification in the response of RyRs to luminal Ca(2+) was not
      observed with heat-inactivated trypsin, indicating that digestion of luminal
      sites on the RyR channel complex was responsible. Our results provide strong
      evidence for the presence of luminally located Ca(2+) activation and inhibition
      sites and indicate that trypsin digestion leads to selective damage to luminal
      Ca(2+) activation sites without affecting luminal Ca(2+) inactivation sites. We
      suggest that changes in luminal [Ca(2+)] will be able to regulate RyR channel
      gating from within the SR lumen, therefore providing a second Ca(2+)-regulatory
      effect on RyR channel gating in addition to that of cytosolic Ca(2+). This
      luminal Ca(2+)-regulatory mechanism is likely to be an important contributing
      factor in the potentiation of SR Ca(2+) release that is observed in cardiac cells
      in response to increases in intra-SR [Ca(2+)].

PMID- 10926871
TI  - Transgenic myocardial overexpression of fibroblast growth factor-1 increases
      coronary artery density and branching.
AB  - Fibroblast growth factor (FGF)-1 plays important roles during myocardial and
      coronary morphogenesis. FGF-1 is also involved in the physiological response of
      the adult heart against ischemia, which includes cardiomyocyte protection and
      vascular growth. In the present study, we have generated transgenic mice with
      specific myocardial overexpression of the gene. Transgene expression was verified
      by Northern blot, and increased FGF-1 protein content was assessed by Western
      blot and immunoconfocal microscopy. Anatomic, histomorphological, and
      ultrastructural analyses revealed no major morphological or developmental
      abnormalities of transgenic hearts. Capillary density was unaltered, whereas the
      density of coronary arteries, especially arterioles, was significantly increased,
      as was the number of branches of the main coronary arteries. In addition, the
      coronary flow was significantly enhanced in transgenic mice ex vivo. These
      differences in the anatomic pattern of the coronary vasculature are established
      during the second month of postnatal life. The present findings demonstrate an
      important role of FGF-1 in the differentiation and growth of the coronary system
      and suggest that it is a key regulatory molecule of the differentiation of the
      arterial system.

PMID- 10926872
TI  - 1 alpha,25-dihydroxyvitamin D(3) inhibits angiogenesis in vitro and in vivo.
AB  - Modulation of angiogenesis is now a recognized strategy for the prevention and
      treatment of pathologies categorized by their reliance on a vascular supply. The
      purpose of this study was to evaluate the effect of 1 alpha,25-dihydroxyvitamin
      D(3) [1, 25(OH)(2)D(3)], the active metabolite of vitamin D(3), on angiogenesis
      by using well-characterized in vitro and in vivo model systems. 1,25(OH)(2)D(3)
      (1 x 10(-9) to 1 x 10(-7) mol/L) significantly inhibited vascular endothelial
      growth factor (VEGF)-induced endothelial cell sprouting and elongation in vitro
      in a dose-dependent manner and had a small, but significant, inhibitory effect on
      VEGF-induced endothelial cell proliferation. 1, 25(OH)(2)D(3) also inhibited the
      formation of networks of elongated endothelial cells within 3D collagen gels. The
      addition of 1, 25(OH)(2)D(3) to endothelial cell cultures containing sprouting
      elongated cells induced the regression of these cells, in the absence of any
      effect on cells present in the cobblestone monolayer. Analysis of nuclear
      morphology, DNA integrity, and enzymatic in situ labeling of apoptosis-induced
      strand breaks demonstrated that this regression was due to the induction of
      apoptosis specifically within the sprouting cell population. The effect of
      1,25(OH)(2)D(3) on angiogenesis in vivo was investigated by using a model in
      which MCF-7 breast carcinoma cells, which had been induced to overexpress VEGF,
      were xenografted subcutaneously together with MDA-435S breast carcinoma cells
      into nude mice. Treatment with 1,25(OH)(2)D(3) (12.5 pmol/d for 8 weeks) produced
      tumors that were less well vascularized than tumors formed in mice treated with
      vehicle alone. These results highlight the potential use of 1,25(OH)(2)D(3) in
      both the prevention and regression of conditions characterized by pathological
      angiogenesis.

PMID- 10926873
TI  - Role for G(12)/G(13) in agonist-induced vascular smooth muscle cell contraction.
AB  - Receptor-induced vascular smooth muscle cell contraction is mediated by dual
      regulation of myosin light chain (MLC(20)) phosphorylation through Ca(2+)
      dependent stimulation of myosin light chain kinase and Rho/Rho-kinase-mediated
      inhibition of myosin phosphatase. Although myosin light chain kinase regulation
      is initiated by the coupling of receptors to G proteins of the G(q) family, G(q)
      and G(11), it is not known how receptors regulate the Rho/Rho-kinase-mediated
      pathway. In vascular smooth muscle cells, receptor-mediated MLC(20)
      phosphorylation and cell contraction was blocked by inhibitors of each of the
      pathways. Receptors of various vasocontractors were found to couple to G(q)/G(11)
      and G(12)/G(13), and constitutively active forms of G alpha(12) and G alpha(13)
      induced a pronounced contraction of vascular smooth muscle cells that could be
      blocked by C3 exoenzyme, by inhibition of Rho-kinase, and by stable analogues of
      cGMP and cAMP. Receptor-mediated smooth muscle cell contraction was strongly
      inhibited by dominant-negative forms of G alpha(12) and G alpha(13). These data
      indicate that a G(12)/G(13)-mediated Rho/Rho-kinase-dependent pathway operates in
      smooth muscle cells and that dual regulation of MLC(20) phosphorylation by
      vasocontractors is initiated by the dual coupling of their receptors to G
      proteins of the G(q) and G(12) families.

PMID- 10926874
TI  - Stretch-dependent modulation of contractility and growth in smooth muscle of rat
      portal vein.
AB  - Increased intraluminal pressure of the rat portal vein in vivo causes hypertrophy
      and altered contractility in 1 to 7 days. We have used organ cultures to
      investigate mechanisms involved in this adaptation to mechanical load. Strips of
      rat portal vein were cultured for 3 days, either undistended or loaded by a
      weight. Length-force relations were shifted toward longer length in stretched
      cultured veins compared with freshly dissected veins, whereas the length-force
      relations of unstretched cultured veins were shifted in the opposite direction.
      This occurred after culture either with or without 10% FCS to promote growth. The
      wet weight of loaded veins increased by 56% in the presence of FCS, whereas that
      of undistended control veins increased by 24%. No weight increase was seen in
      serum-free culture. The dry/wet weight ratio decreased during culture with FCS
      but was not affected by stretch. Electron microscopy revealed increased cell
      cross-sectional area in stretched relative to unstretched veins, and protein
      contents were greater, as were [(3)H]thymidine and [(3)H]leucine incorporation
      rates. Growth responses were associated with the activation of stretch-sensitive
      extracellular signal-regulated kinases 1 and 2 and were inhibited by herbimycin A
      and PD 98059, inhibitors of extracellular signal-regulated kinases 1 and 2. The
      results demonstrate that by culture of whole vascular tissue, smooth muscle cells
      are maintained in the contractile phenotype and respond to stretch with a
      physiological adaptation involving hypertrophy/hyperplasia and remodeling of the
      contractile system, similar to that in vivo. Mechanical stimulation and growth
      factors are both required for functionally significant growth.

PMID- 10926875
TI  - Alterations in the determinants of diastolic suction during pacing tachycardia.
AB  - In cardiomyocytes, generation of restoring forces (RFs) responsible for elastic
      recoil involves deformation of the sarcomeric protein titin in conjunction with
      shortening below slack length. At the left ventricular (LV) level, recoil and
      filling by suction require contraction to an end-systolic volume (ESV) below
      equilibrium volume (Veq) as well as large-scale deformations, for example,
      torsion or twist. Little is known about RFs and suction in the failing ventricle.
      We undertook a comparison of determinants of suction in open-chest dogs
      previously subjected to 2 weeks of pacing tachycardia (PT) and controls. To
      assess the ability of the LV to contract below Veq, we used a servomotor to clamp
      left atrial pressure and produce nonfilling diastoles, allowing measurement of
      fully relaxed pressure at varying volumes. We quantified twist with
      sonomicrometry. We also assessed transmural ratios of N2B to N2BA titin isoforms
      and total titin to myosin heavy chain (MHC) protein. In PT, the LV did not
      contract below Veq, even with marked reduction of volume (end-diastolic pressure
      [EDP], 1 to 2 mm Hg), whereas in controls ESV was less than Veq when EDP was less
      than approximately 5 mm Hg. In PT, both systolic twist and diastolic untwisting
      rate were reduced, and there was exaggerated transmural variation in titin
      isoform and titin-to-MHC ratios, consistent with the more extensible N2BA being
      present in larger amounts in the subendocardium. Thus, in PT, determinants of
      suction at the level of the LV are markedly impaired. The altered transmural
      titin isoform gradient is consistent with a decrease in RFs and may contribute to
      these findings.

PMID- 10926876
TI  - Peroxynitrite is a major contributor to cytokine-induced myocardial contractile
      failure.
AB  - Proinflammatory cytokines depress myocardial contractile function by enhancing
      the expression of inducible NO synthase (iNOS), yet the mechanism of iNOS
      mediated myocardial injury is not clear. As the reaction of NO with superoxide to
      form peroxynitrite markedly enhances the toxicity of NO, we hypothesized that
      peroxynitrite itself is responsible for cytokine-induced cardiac depression.
      Isolated working rat hearts were perfused for 120 minutes with buffer containing
      interleukin-1 beta, interferon-gamma, and tumor necrosis factor-alpha. Cardiac
      mechanical function and myocardial iNOS, xanthine oxidoreductase (XOR), and
      NAD(P)H oxidase activities (sources of superoxide) were measured during the
      perfusion. Cytokines induced a marked decline in myocardial contractile function
      accompanied by enhanced activity of myocardial XOR, NADH oxidase, and iNOS.
      Cardiac NO content, myocardial superoxide production, and perfusate nitrotyrosine
      and dityrosine levels, markers of peroxynitrite, were increased in cytokine
      treated hearts. The peroxynitrite decomposition catalyst FeTPPS (5,10,15, 20
      tetrakis-[4-sulfonatophenyl]-porphyrinato-iron[III]), the NO synthase inhibitor
      N(G)-nitro-L-arginine, and the superoxide scavenger tiron each inhibited the
      decline in myocardial function and decreased perfusate nitrotyrosine levels.
      Proinflammatory cytokines stimulate the concerted enhancement in superoxide and
      NO-generating activities in the heart, thereby enhancing peroxynitrite
      generation, which causes myocardial contractile failure.

PMID- 10926877
TI  - Accelerated atherosclerosis by placement of a perivascular cuff and a cholesterol
      rich diet in ApoE*3Leiden transgenic mice.
AB  - Intimal hyperplasia after vascular injury is usually studied in animal models
      with healthy, normocholesterolemic animals. Here, we assess the effect of diet
      induced hypercholesterolemia on the induction of intimal hyperplasia in
      ApoE*3Leiden mice. A nonconstrictive polyethylene cuff was placed around the
      femoral artery of ApoE3*Leiden mice fed a highly cholesterol-rich diet, a mildly
      cholesterol-rich diet, or a chow diet for 4 weeks. Diets were continued after
      cuff placement until euthanization. At several time points (1 to 14 days), mice
      were euthanized and the intimal hyperplasia in the cuffed arteries was analyzed.
      In mice fed a chow diet, a 2- to 4-cell-layer-thick intima, predominantly
      consisting of alpha smooth muscle cell actin-positive cells, was observed after
      14 days. A mildly cholesterol-rich diet (mean plasma-cholesterol level, 10.5
      mmol/L) resulted in a 2.7-fold increase of total intimal area, and a highly
      cholesterol-rich diet (mean plasma cholesterol level 28. 6 mmol/L), in a 7.8-fold
      increase. In the high-cholesterol group, the intima consisted predominantly of
      lipid-loaded foam cells and alpha smooth muscle cell actin-positive cells. Foam
      cell accumulation could be observed by as early as 3 days, resulting in a near
      total occlusion of the lumen after 14 days. Hypercholesterolemia resulted in a
      rapid, cholesterol-dependent induction of foam cell-rich intimal hyperplasia in
      cuffed femoral arteries of ApoE*3Leiden mice. In conclusion, the present data
      show that the combination of a local (cuff placement) and a systemic
      (hypercholesterolemic) risk factor of atherosclerosis results in a rapid
      induction (within 14 days) of atherosclerotic-like lesions in ApoE*3Leiden mice.

PMID- 10926878
TI  - beta(2)-Integrin blockade driven by E-selectin promoter prevents neutrophil
      sequestration and lung injury in mice.
AB  - Interaction of CD11/CD18 beta(2) integrins on polymorphonuclear leukocytes (PMNs)
      with their counterreceptor, intercellular adhesion molecule-1, on the surface of
      vascular endothelial cells is a critical event mediating stable PMN adhesion and
      migration across the pulmonary vascular endothelial barrier. Neutrophil
      inhibitory factor (NIF), a 41-kDa glycoprotein isolated from the canine hookworm
      (Ancylostoma caninum), binds to the I domain of CD11a and CD11b and inhibits
      beta(2) integrin-dependent PMN adhesion. We describe a novel strategy using the
      endothelial cell-specific E-selectin promoter to induce NIF expression in an
      inflammation-specific manner in pulmonary vascular endothelial cells. A construct
      containing NIF cDNA driven by the inducible endothelial cell-specific E-selectin
      promoter (pESNIF) was transfected into human pulmonary artery endothelial cells
      (HPAECs). Lipopolysaccharide challenge (known to activate E-selectin) resulted in
      NIF mRNA and protein expression in transfected HPAECs. NIF expression induced by
      the E-selectin promoter prevented PMN adhesion to the activated HPAECs, whereas
      PMNs adhered avidly to activated HPAECs in the absence of NIF expression. To
      address the utility of this approach in conditionally preventing in vivo PMN
      sequestration, we injected mice intravenously with cationic liposomes containing
      the pESNIF construct. Analysis of lung tissue showed that intraperitoneal
      challenge of Escherichia coli resulted in NIF expression. Inflammation-specific
      NIF expression induced by the E-selectin promoter prevented lung PMN
      sequestration and vascular injury induced by E coli challenge. These studies
      suggest the feasibility of conditionally blocking beta(2) integrin function at
      sites where the endothelium is activated and thereby of locally preventing PMN
      activation and migration responses that lead to tissue inflammation.

PMID- 10926880
TI  - Molecular testing of urine: catching DNA on the way out.

PMID- 10926879
TI  - Interferences in immunoassay--still a threat.

PMID- 10926881
TI  - Evidence-based laboratory medicine: supporting decision-making.
AB  - There is an implicit acceptance that an evidence-based culture underpins the
      practice of laboratory medicine, in part because it is perceived as the
      scientific foundation of medicine. However, several reviews of specific test
      procedures or technologies have shown that the evidence base is limited and in
      many cases flawed. One of the key deficiencies in the scientific literature on
      diagnostic tests often is the absence of an explicit statement of the clinical
      need, i.e., the clinical or operational question that the use of the test is
      seeking to answer. Several reviews of the literature on specific procedures have
      also demonstrated that the experimental methodology used is flawed with, in some
      cases, significant bias being introduced. Despite these limitations it is
      recognized that a more evidence-based approach will help in the education and
      training of health professionals, in the creation of a research agenda, in the
      production of guidelines, in the support of clinical decision-making, and in
      resource allocation. Furthermore, as knowledge and technologies continue to be
      developed, an evidence-based strategy will be critical to harnessing these
      developments.

PMID- 10926882
TI  - Genotyping of factor V G1691A (Leiden) without the use of PCR by invasive
      cleavage of oligonucleotide probes.
AB  - BACKGROUND: The factor V G1691A Leiden (FVL) mutation is the most common known
      hereditary risk factor for venous thrombosis. METHODS: Third Wave Technologies,
      Inc. (Madison, WI) has developed a new microtiter plate-based assay that does not
      require PCR, restriction digestion, or gel electrophoresis. This technology
      system, termed the Invader(TM) assay, utilizes a 5' "invading" oligonucleotide
      and a partially overlapping 3' "signal" oligonucleotide, which together form a
      specific structure when bound to a complementary genomic DNA template. A
      thermostable flap endonuclease cleaves this structure, releasing the 5' flap from
      the signal oligonucleotide. Increased temperature and an excess of the signal
      probe enable multiple probes to be cleaved for each target sequence present
      without temperature cycling. The cleaved probes then direct cleavage of a
      secondary probe, which is 5' end-labeled with fluorescein but is quenched by an
      internal dye. Upon cleavage, the fluorescein-labeled product is detected using a
      standard fluorescence plate reader. Genotypes are determined by net wild
      type/mutant signal ratio. RESULTS: Complete concordance was observed, after
      resolution of four discordances, when 1369 individuals (1264 wild type, 102
      heterozygous, 3 homozygous) were FVL genotyped by both the Invader assay and by
      allele-specific PCR. CONCLUSION: We conclude that FVL genotyping using invasive
      cleavage of oligonucleotide probes is a rapid and reliable alternative to
      genotyping by more traditional PCR-based methods.

PMID- 10926883
TI  - Flow cytometric analysis of reverse transcription-PCR products: quantification of
      p21(WAF1/CIP1) and proliferating cell nuclear antigen mRNA.
AB  - BACKGROUND: Reverse transcription-PCR (RT-PCR) is a powerful tool in clinical
      diagnostics for analyzing even small amounts of RNA, but sensitive assays for
      quantifying the amplification products are time-consuming or expensive. Here we
      describe a novel flow cytometry-based assay for rapid and sensitive determination
      of relative amounts of RT-PCR products. METHODS: For flow cytometric
      quantification, PCR products were labeled with both digoxigenin and biotin during
      amplification. Subsequently, amplicons were simultaneously bound to anti
      digoxigenin microparticles and fluorescently labeled with streptavidin-R
      phycoerythrin. Fluorescence intensity per bead was determined by flow cytometry.
      To study this assay, we examined the expression of the p21(WAF1/CIP1) gene and
      the proliferating cell nuclear antigen (PCNA) gene in ultraviolet irradiation
      exposed human keratinocytes lacking functional p53. RESULTS: Fluorescence was
      linear with 60-10 000 pg of PCR product. As little as 0.4 fmol (40 pg of a 163-bp
      amplicon) of PCR product could be distinguished from background. The between-run
      CV of the fluorescent signal for 10 ng of p21 cDNA was 12% (n = 10). The
      fluorescence-template curve was sigmoidal. p21(WAF1/CIP1) mRNA was decreased
      after ultraviolet irradiation of keratinocytes, whereas PCNA mRNA was markedly
      increased. CONCLUSION: The flow cytometric assay permits rapid (25 min) and
      reproducible identification of changes in mRNA abundance.

PMID- 10926884
TI  - Riboflavin as a determinant of plasma total homocysteine: effect modification by
      the methylenetetrahydrofolate reductase C677T polymorphism.
AB  - BACKGROUND: Plasma total homocysteine (tHcy) is a risk factor for cardiovascular
      disease. tHcy concentrations are partly determined by folate, cobalamin, and
      vitamin B(6) status, and methylenetetrahydrofolate reductase (MTHFR) and other
      flavoenzymes are important for the biotransformation of these vitamins. This
      motivates the investigation of the possible relationship between riboflavin
      status and tHcy. METHODS: The study had a cross-sectional design and included 423
      healthy blood donors, ages 19-69 years. We determined plasma tHcy, serum folate,
      serum cobalamin, serum creatinine, and MTHFR C677T genotype. In addition, we
      measured riboflavin and its two coenzyme forms, flavin mononucleotide and flavin
      adenine dinucleotide, in EDTA plasma by capillary electrophoresis and laser
      induced fluorescence detection. RESULTS: Riboflavin determined tHcy independently
      in a multiple linear regression model with adjustment for sex, age, folate,
      cobalamin, creatinine, and MTHFR genotype (P = 0.008). tHcy was 1.4 micromol/L
      higher in the lowest compared with the highest riboflavin quartile. The
      riboflavin-tHcy relationship was modified by genotype (P = 0.004) and was
      essentially confined to subjects with the C677T transition of the MTHFR gene.
      CONCLUSIONS: Plasma riboflavin is an independent determinant of plasma tHcy.
      Studies on deficient populations are needed to evaluate the utility of riboflavin
      supplementation in hyperhomocysteinemia.

PMID- 10926885
TI  - Rapid detection of the CYP2D6*3, CYP2D6*4, and CYP2D6*6 alleles by tetra-primer
      PCR and of the CYP2D6*5 allele by multiplex long PCR.
AB  - BACKGROUND: Interindividual differences in CYP2D6 activity range from total
      absence of metabolism of certain drugs to ultrafast metabolism and can produce
      adverse effects or lack of therapeutic effect under standard therapy. Several
      mutations have been described in the CYP2D6 gene that abolish CYP2D6 activity.
      However, four mutations explain the majority of the poor metabolizers. We
      describe four single-tube assays to detect these mutations. METHODS: Three tetra
      primer PCR assays were developed to detect the mutations in the CYP2D6*3, *4, and
      *6 alleles. In these single-tube assays, the CYP2D6 locus is amplified directly,
      followed by the allele-specific amplification on this new template. In addition,
      a multiplex long PCR was developed to genotype the CYP2D6*5 allele. Two long PCR
      amplifications for detection of the deletion of CYP2D6 (*5) and for detection of
      the CYP2D6 gene region were combined in one tube. RESULTS: Analysis of 114
      alleles showed no CYP2D6*3 allele, and allele frequencies of 28.1% for CYP2D6*4,
      2.6% for CYP2D6*5, and 0. 9% for CYP2D6*6. Re-analysis of the DNA samples by
      restriction fragment length polymorphism and sequencing analysis confirmed these
      results. Furthermore, re-analysis of sequenced genomic DNA by tetra-primer PCR
      analysis (7-11 times) always showed identical results. CONCLUSIONS: Our set of
      single-tube assays allows rapid and reproducible genotyping of the majority of
      CYP2D6 poor metabolizers.

PMID- 10926886
TI  - Genetic analysis of DNA excreted in urine: a new approach for detecting specific
      genomic DNA sequences from cells dying in an organism.
AB  - BACKGROUND: Cell-free DNA from dying cells recently has been discovered in human
      blood plasma. In experiments performed on animals and humans, we examined whether
      this cell-free DNA can cross the kidney barrier and be used as a diagnostic tool.
      METHODS: Mice received subcutaneous injections of either human Raji cells or
      purified (32)P-labeled DNA. DNA was isolated from urine and analyzed by
      measurement of radioactivity, agarose gel electrophoresis, and PCR. In humans,
      the permeability of the kidney barrier to polymeric DNA was assessed by detection
      in urine of sequences that were different from an organism bulk nuclear DNA.
      RESULTS: In the experiments on laboratory animals, we found that approximately
      0.06% of injected DNA was excreted into urine within 3 days in a polymeric form
      and that human-specific ALU: sequences that passed through the kidneys could be
      amplified by PCR. In humans, male-specific sequences could be detected in the
      urine of females who had been transfused with male blood as well as in DNA
      isolated from urine of women pregnant with male fetuses. K-ras mutations were
      detected in the urine of patients with colon adenocarcinomas and pancreatic
      carcinomas. CONCLUSIONS: The data suggest that the kidney barrier in rodents and
      humans is permeable to DNA molecules large enough to be analyzed by standard
      genetic methodologies.

PMID- 10926887
TI  - Analytical quality of near-patient blood cholesterol and glucose determinations.
AB  - BACKGROUND: Screening for diabetes and hypercholesterolemia is widely advocated,
      and extra-laboratory testing could play a major role in cost-effective population
      screening. We wished to assess the analytical quality and interchangeability of
      capillary blood cholesterol and glucose assays as performed on near-patient
      devices in pharmacies in Pretoria, South Africa. METHODS: Accuracy of near
      patient and laboratory analyzers was assessed by analyses of human-serum-based
      reference material. To assess interchangeability in routine use, six volunteers
      visited each of 12 randomly selected pharmacies consecutively during a 3-week
      period to have their fasting blood glucose and cholesterol concentrations
      determined. For comparison purposes, a similar procedure was followed to evaluate
      the eight clinical chemistry laboratories servicing Pretoria and surroundings.
      RESULTS: The analytical performances in our laboratory of a single point-of-care
      instrument and of a laboratory analyzer compared well. Nevertheless, between
      pharmacy analytical variation was larger than between-laboratory variation (11%
      vs 6.1% for cholesterol; 10% vs 7.6% for glucose). For glucose measurements, near
      patient testing in pharmacies demonstrated a bias of -48.1% to 16.2%, whereas
      bias for laboratory measurements was -1.0% to 7.4%. Cholesterol assays showed a
      bias of -5.6% to 16.6% in pharmacies compared with -10.6% to 3.7% in
      laboratories. The percentage of closeness to the homeostatic set point for a
      single glucose and cholesterol determination done in any pharmacy was 24.6% and
      23.6%, respectively. The corresponding values for laboratories were 16.9% and
      15.6%, respectively. CONCLUSIONS: Although modern point-of-care instruments allow
      high-quality blood analyses under ideal conditions, performance goals often are
      not achieved in practice as indicated by a higher uncertainty of cholesterol and
      glucose blood results when determined in pharmacies. Nonuniformity of calibration
      procedures, deficiencies in training, a lack of internal quality control, and the
      absence of an external quality assessment program may all contribute to the
      current state of affairs.

PMID- 10926888
TI  - Opportunistic discovery of occult disease by use of test panels in new,
      symptomatic primary care outpatients: yield and cost of case finding.
AB  - BACKGROUND: Diagnostic test panels have been advocated by the Japan Society of
      Clinical Pathology for evaluation of presenting complaints of new outpatients in
      primary care medicine. The tests have additional potential utility for
      opportunistic finding of asymptomatic diseases, but data are lacking on the
      number of new conditions identified by the test panels and on the cost per
      identified case. METHODS: We studied 540 new, symptomatic patients at the
      Comprehensive Medicine Clinics of National Defense Medical College during 1991
      1997. All underwent testing with the "Essential Laboratory Tests" panel (2)
      [ELT(2) panel]. This panel includes hematologic tests, urinalysis, total protein,
      C-reactive protein, albumin, cholesterol, triglycerides, glucose, urea nitrogen,
      creatinine, uric acid, serum protein fractionation, six enzymes, and optional
      tests, including x-rays, electrocardiogram, and fecal occult blood. RESULTS: The
      ELT(2) panel uncovered 276 additional diagnoses of asymptomatic disease or
      abnormal health status. The most frequent occult condition was hyperlipidemia
      (100 cases) followed by liver dysfunction (53 cases). Clinical efficiency of the
      panel (occult diseases/patient) varied depending on the category of tentative
      initial diagnosis, with the highest efficiency in patients with cardiovascular
      disease. We created smaller panels by combining 11 basic tests [called the ELT(1)
      baseline panel] with one or more additional tests from the ELT(2) and analyzed
      their cost-effectiveness. Addition of four tests (total cholesterol, alanine
      aminotransferase, glucose, and uric acid) improved both clinical efficiency (0.41
      occult disease/patient) and economic efficiency [ 2372 yen (approximately $22.50
      US)/occult disease] at a cost-effectiveness of 177 yen per incremental case of
      occult disease. Addition of further tests decreased cost-effectiveness.
      CONCLUSIONS: Although the ELT(2) panel has supplemental utility for opportunistic
      screening of some significant, occult diseases and conditions, universal
      utilization of the full panel is not supported by the cost-effectiveness found in
      this study.

PMID- 10926889
TI  - Quantification and characterization of pregnancy-associated complexes of
      angiotensinogen and the proform of eosinophil major basic protein in serum and
      amniotic fluid.
AB  - BACKGROUND: The proform of eosinophil major basic protein (ProMBP) exists in
      serum from pregnant women complexed with a variable fraction of angiotensinogen
      (Ang). A subfraction further binds complement C3dg in a 2:2:2 complex. The
      function, physiology, and clinical importance of ProMBP complexes are unknown,
      and the specific quantification of these complexes has not been possible.
      METHODS: We developed an ELISA for the ProMBP/Ang complexes, using a monoclonal
      antibody against ProMBP for capture and a chicken anti-human Ang antiserum for
      detection. Calibrators were standardized with WHO IRP 78/610 for pregnancy
      proteins in the assay range 0.95-15.6 mIU/L. RESULTS: The concentrations of
      ProMBP/Ang complexes in serum of nonpregnant blood donors (n = 79) were log
      normally distributed with a central 95th interval of 985-3655 mIU/L. In
      pregnancy, mean serum concentrations were increased from week 7, and the
      concentrations reached term concentrations in week 18. ProMBP/Ang complexes
      eluted in gel filtration as a broad peak with a molecular mass of approximately
      230 kDa. The concentration of ProMBP/Ang/C3dg increased during blood coagulation,
      suggesting that the ProMBP/Ang/C3dg complex may be a marker of complement
      activation. CONCLUSIONS: ProMBP/Ang complexes are present in serum from
      nonpregnant persons as well as pregnant women, and the direct assays described
      here will make it possible to study the biochemistry and the clinical
      significance of different ProMBP complexes in pathological conditions and
      pregnancy.

PMID- 10926890
TI  - Description of a computer program to assess cancer antigen 15.3, carcinoembryonic
      antigen, and tissue polypeptide antigen information during monitoring of
      metastatic breast cancer.
AB  - It is time-consuming to process and compare the clinical and marker information
      registered during monitoring of breast cancer patients. To facilitate the
      assessment, we developed a computer program for interpreting consecutive
      measurements. The intraindividual biological variation, the analytical precision
      profile, the cutoff limit, and the detection limit for each marker are entered
      and stored in the program. The assessment procedure for marker signals considers
      the analytical and biological variation of the applied markers. The software
      package contains a database that can store the interpretation of the measurements
      as evaluation codes together with patient demographics, information about
      treatment type, dates for treatment periods, control periods, and evaluation
      codes for clinical activity of disease. The consecutive concentrations for a
      patient are imported temporarily into the program from outside sources and
      presented graphically. Marker concentrations to be compared are selected with the
      computer mouse and the significance of the difference is calculated by the
      program. The program has an option for calculating the lead time of marker
      signals vs clinical information. The program facilitates the monitoring of
      individual breast cancer patients with tumor marker measurements. It may also be
      implemented in trials investigating the utility of potential new markers in
      breast cancer as well as in other malignancies.

PMID- 10926891
TI  - Prognostic significance of low serum cholesterol after cardiothoracic surgery.
AB  - BACKGROUND: The precise prognostic significance of critically low cholesterol
      concentrations in patients undergoing cardiothoracic surgery is unknown. METHODS:
      In a retrospective case-control study, we analyzed the database of 2074 patients,
      of whom 87 died postoperatively in hospital. All patients underwent
      cardiothoracic surgery using a heart-lung machine. Age, sex, body mass index,
      preoperative ejection fraction, smoking, diabetes mellitus, type of operation,
      emergency surgery, renal deficiency, pulmonary hypertension, and endocarditis
      were considered together with serum concentrations of cholesterol, C-reactive
      protein, alanine aminotransferase, and triglycerides. The statistics included
      sensitivity, specificity, predictive value, odds ratio, and the ROC curve.
      RESULTS: Cholesterol decreased sharply immediately after surgery in both the
      deceased and the survivors. In the deceased, the mean cholesterol concentration
      (+/- SE) remained rather low between days 4 and 7 after surgery [2.46 +/- 0.16
      mmol/L (95 +/- 6 mg/dL)]. In the survivors at that time, the mean cholesterol
      concentration was significantly (P <0.001) higher [4.37 +/- 0.03 mmol/L (169 +/-
      1 mg/dL)]. The positive predictive value of a critically low cholesterol
      concentration [<3.10 mmol/L (<120 mg/dL)] was 25.4%, increasing to 66.6% at a
      cutoff value of 1.55 mmol/L (60 mg/dL). The odds ratio under those circumstances
      was 15.5, and the area under curve (C-statistic) was 0.90. CONCLUSIONS: The
      cholesterol concentration between days 4 and 7 after cardiothoracic surgery
      possesses a high prognostic significance in terms of in-hospital mortality.

PMID- 10926892
TI  - Analytical and clinical evaluation of two homogeneous assays for LDL-cholesterol
      in hyperlipidemic patients.
AB  - BACKGROUND: LDL-cholesterol (LDL-C) concentrations are the primary basis for
      treatment guidelines established for hyperlipidemic patients. LDL-C
      concentrations are commonly monitored by means of the Friedewald formula, which
      provides a relative estimation of LDL-C concentration when the triglyceride
      concentration is <2000 mg/L and there are no abnormal lipids. The Friedewald
      formula has several limitations and may not meet the current total error
      requirement of <12% in LDL-C measurements. METHODS: We evaluated the analytical
      and clinical performance of two direct methods (Roche and Wako) by analyzing 313
      fresh serum samples obtained from dyslipidemic patients in a lipid clinic and
      comparing them with modified beta-quantification. RESULTS: Both homogeneous
      assays displayed excellent precision (CV <2%). The Roche method showed a mean
      total error of 7.72%, and the Wako method showed a mean total error of 4.46% over
      a wide range of LDL-C concentrations. The Roche method correlated highly with the
      modified beta-quantification assay (r = 0.929; y = 1.052x - 168 mg/L; n = 166)
      and showed a bias of -4. 5% as a result of the assigned standard value. The Wako
      method also correlated highly with beta-quantification (r = 0.966; y = 0.9125x +
      104.8 mg/L; n = 145) without significant bias. The Roche method correctly
      classified 97% of patients with triglycerides <2000 mg/L, 75% of patients with
      type IIb hyperlipemia (HPL), and 84% of patients with type IV HPL based on the
      cutpoints of 1300 and 1600 mg/L, compared with 98%, 78.4%, and 89%, respectively,
      for the Wako method. In dysbetalipoproteinemic patients, both methods have a 30%
      mean positive bias compared with beta-quantification. CONCLUSIONS: Both direct
      methods can be a useful alternative when ultracentrifugation is not available for
      the diagnosis and control of lipid-lowering medication for patients with mixed
      HPL, but not for patients with type III hyperlipidemia.

PMID- 10926893
TI  - Evidence-based implementation of free phenytoin therapeutic drug monitoring.
AB  - BACKGROUND: The majority of laboratories measure total phenytoin concentration
      for therapeutic drug monitoring. However, there are substantial interindividual
      variations in free phenytoin concentrations, the pharmacologically active
      component. METHODS: We describe the process and data used to implement monitoring
      of free phenytoin only in an urban medical center. Over a 6-week period, total
      and free phenytoin concentrations were measured, clinical charts reviewed, and
      indications for alterations in the percentage of free phenytoin fraction were
      determined. RESULTS: Of the 189 phenytoin requests from 139 patients, 136 data
      points were analyzed. Free phenytoin concentrations were 6.8-35.3%, with 50%
      outside the expected range of 8-12%. Clinical indications likely responsible for
      variations were hypoalbuminemia, drug interactions, uremia, pregnancy, and age.
      Overall, 30% of patients demonstrated a discrepancy between therapeutic,
      subtherapeutic, or supratherapeutic concentrations between free and total
      phenytoin concentrations. The largest discordance (53%) occurred in the patient
      group with free phenytoin <8% or >12%. CONCLUSIONS: This study supports previous
      clinical findings that monitoring total phenytoin is not as reliable as free
      phenytoin as a clinical indicator for therapeutic and nontherapeutic
      concentrations. Thus, we recommend that therapeutic monitoring should use free
      phenytoin concentrations only.

PMID- 10926894
TI  - Space flight is associated with rapid decreases of undercarboxylated osteocalcin
      and increases of markers of bone resorption without changes in their circadian
      variation: observations in two cosmonauts.
AB  - BACKGROUND: Microgravity induces bone loss by mechanism(s) that remain largely
      unknown. METHODS: We measured biochemical markers related to bone remodeling in
      two cosmonauts before, during, and after 21- and 180-day space flights,
      respectively. RESULTS: During both flights, type I procollagen propeptide and
      bone alkaline phosphatase decreased as early as 8 days after launch.
      Undercarboxylated osteocalcin percentage increased early and remained high during
      both flights. Vitamin K supplementation restored carboxylation of osteocalcin
      during the long-term flight. Urinary and serum C-telopeptide of type I collagen
      (CTX) increased as early as day 8 of the flights; the increase was greater in
      serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide
      increased less than CTX during the short-term space flight. The circadian rhythm
      of bone resorption assessed by urine CTX and free deoxypyridinoline was not
      altered by microgravity. CONCLUSION: Vitamin K metabolism or action and bone
      remodeling may be altered in cosmonauts.

PMID- 10926895
TI  - Glyceraldehyde preserves glucose concentrations in whole blood specimens.
AB  - BACKGROUND: Glucose concentrations decrease in blood specimens during
      transport/processing, primarily because of continuing metabolism (glycolysis) by
      erythrocytes. Several means to reduce the loss of glucose in blood specimens have
      been developed, but all have major drawbacks. Glyceraldehyde, which has
      antiglycolytic activity, was assessed for potential in preserving glucose in
      blood specimens. METHODS: Heparinized blood from volunteers was treated with
      glyceraldehyde and other agents. After incubation for various times, plasma
      concentrations of glucose and other common analytes were determined with
      prevalent commercial analyzers. RESULTS: The racemic mixture of glyceraldehyde
      (D,L-GA) preserved glucose concentrations for up to 8 h at room temperature. Half
      maximal effect was attained with 0.9 mmol/L D,L-GA. Trials of the D and L
      stereoisomers individually indicated that the L isomer (L-GA) was responsible for
      all or most of the antiglycolytic activity of the racemic mixture. Other related
      compounds were ineffective. Measurements of most common clinical laboratory
      analytes were unaffected by the presence of D,L-GA or L-GA. CONCLUSIONS:
      Glyceraldehyde (D,L-GA or L-GA) effectively preserves glucose concentrations in
      whole blood specimens for up to 8 h. Specimens collected with D,L-GA or L-GA are
      suitable for analysis of many analytes commonly comeasured with glucose.

PMID- 10926896
TI  - Evaluation of novel assays in clinical chemistry: quantification of plasma total
      homocysteine.
AB  - BACKGROUND: There is a need for systematic evaluation of methods before their
      release to the market. We addressed this problem in novel homocysteine assays as
      part of an European Demonstration Project involving six centers in four
      countries. METHODS: Two immunological methods for measurement of plasma total
      homocysteine (P-tHcy), the fluorescence polarization immunoassay (FPIA) and the
      enzyme immunoassay (EIA), were compared with two comparison methods, HPLC and gas
      chromatography-mass spectrometry (GC-MS). All laboratories performed the
      following procedures: (a) familiarization; (b) determination of linearity and
      precision by analyzing five plasma samples with interrelated concentrations for
      20 days; (c) correlation using patients' samples; and (d) assessment of long-term
      performance. RESULTS: Both immunological methods were linear for P-tHcy between 5
      and 45 micromol/L. The intralaboratory imprecision (CV) was <5% for FPIA and <9%
      for EIA used with a sample processor. The bias was -2% to 3% for FPIA and 2-4%
      for EIA used with a sample processor. CONCLUSIONS: The immunological methods
      provide results with little bias compared with HPLC and GC-MS. The imprecision of
      the assays must be considered in the context of their intended use(s).

PMID- 10926897
TI  - An IgM lambda antibody to Escherichia coli produces false-positive results in
      multiple immunometric assays.
AB  - BACKGROUND: Interferences in immunometric assays as a result of human anti
      immunoglobulin antibodies frequently have been described in the literature. The
      etiology of these interfering antibodies is usually not known but has been
      associated with rheumatoid factors in some assays. It is known that
      microorganisms in experimental settings can induce anti-immunoglobulin
      antibodies. METHODS: Following Escherichia coli septicemia, a 56-year-old male
      patient had increased immunoassay results for cardiac troponin I, thyrotropin,
      human chorionic gonadotropin, alpha-fetoprotein, and CA-125 that were consistent
      with myocardial infarction, hyperthyroidism, and pregnancy, and suggestive of an
      occult neoplasm such as hepatic or ovarian cancer. None of these diagnoses were
      consistent with the rest of his medical exam. In addition, the patient had a
      restricted IgM lambda paraprotein by immunofixation. Plasma from the patient was
      incubated with Sepharose-conjugated protein A, irrelevant murine monoclonal
      antibodies, and formalin-killed E. coli organisms from his infection to determine
      whether these immunoassay values were falsely increased. RESULTS: Incubation of
      the patient's plasma with irrelevant murine monoclonal antibodies or the E. coli
      organism produced normal immunoassay values and removed the IgM lambda
      paraprotein. CONCLUSIONS: The patient produced a very restricted IgM lambda
      antibody response to the E. coli infection that had anti-immunoglobulin activity
      and caused falsely increased values in numerous immunometric assays.
      Microorganism-induced anti-immunoglobulin antibodies are discussed in the context
      of this patient.

PMID- 10926899
TI  - Bone lead concentrations assessed by in vivo X-ray fluorescence.
AB  - The assessment of past chronic lead exposure is difficult. Chronic lead burden is
      not always correctly assessed using laboratory-based tests that are useful for
      acute or recent exposures. We describe a case of suspected chronic lead exposure
      that illustrated the need for improved and possibly noninvasive methods to
      determine cumulative lead body burden. X-Ray fluorescence (XRF) is discussed as a
      method to obtain in vivo bone lead measurements. We discuss the potential of such
      measurements as accurate biomarkers of cumulative exposure and whether XRF can be
      used for retroactive exposure assessment or to predict risk of future health
      problems.

PMID- 10926898
TI  - Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without
      affecting plasma antioxidant vitamin and carotenoid concentrations.
AB  - BACKGROUND: Antioxidant enrichment of LDL can increase its resistance to
      oxidation and hence reduce its atherogenicity. The objective of the present study
      was to investigate whether in vivo supplementation with nonalcoholic red wine
      extract and quercetin can increase the oxidative resistance of LDL, and also
      whether the supplementation has any effect on other antioxidative micronutrients
      present in the blood. METHODS: Twenty-one male subjects were supplemented with a
      placebo drink for 2 weeks and randomized into two groups. One group (n = 11)
      received the red wine extract (1 g/day, equivalent to 375 mL of red wine) and the
      other group (n = 10) quercetin (30 mg/day) for 2 weeks, followed by a 5-week
      washout period. RESULTS: In the red wine extract-supplemented group, ex vivo
      copper-initiated oxidation of LDL (lag phase, mean +/- SD) was 40 +/- 11 min at
      the baseline, and increased significantly to 47 +/- 6 min [P <0.05 compared with
      placebo (38 +/- 4 min) and the washout values (40 +/- 5 min)]. In the quercetin
      supplemented group, the lag phase was 44 +/- 11 and 40 +/- 5 min for the baseline
      and placebo, respectively, and increased significantly to 51 +/- 7 min [P <0.05
      compared with placebo and washout (41 +/- 9 min)] after supplementation. Plasma
      lipids (triglycerides, total cholesterol, LDL- and HDL-cholesterol) did not
      change during the study period. Supplementation with red wine extract or
      quercetin had no effect on plasma vitamin C and E, retinol, and carotenoid
      concentrations. CONCLUSIONS: Alcohol-free red wine extract and one of its
      components, quercetin, can inhibit LDL oxidation after in vivo supplementation;
      such "inhibition" is unrelated to changes in antioxidant vitamin and carotenoid
      concentrations.

PMID- 10926900
TI  - Validation of an assay for routine monitoring of sirolimus using HPLC with mass
      spectrometric detection.

PMID- 10926901
TI  - Identification of two LDL-receptor mutations causing familial
      hypercholesterolemia in Indian subjects by a simplified rapid PCR-heteroduplex
      method.

PMID- 10926902
TI  - Does iron concentration in a liver needle biopsy accurately reflect hepatic iron
      burden in beta-thalassemia?

PMID- 10926903
TI  - Agreement study of methods based on the elimination principle for the measurement
      of LDL- and HDL-cholesterol compared with ultracentrifugation in patients with
      liver cirrhosis.

PMID- 10926904
TI  - Rapid single-tube genotyping of the factor V Leiden and prothrombin mutations by
      real-time PCR using dual-color detection.

PMID- 10926905
TI  - Colorimetric microwell plate detection of the factor V Leiden mutation.

PMID- 10926906
TI  - Ischemic exercise testing in suspected McArdle disease.

PMID- 10926907
TI  - A simple PCR-heteroduplex screening method for detection of a common mutation of
      the catalase gene in Hungary.

PMID- 10926908
TI  - Stability of several biochemical markers of bone metabolism.

PMID- 10926909
TI  - LDL particle size by gradient-gel electrophoresis cannot be estimated by LDL
      cholesterol/apolipoprotein B ratios.

PMID- 10926910
TI  - Does trisialo-transferrin provide valuable information for the laboratory
      diagnosis of chronically increased alcohol consumption by determination of
      carbohydrate-deficient transferrin?

PMID- 10926911
TI  - Plasma cystatin C is superior to 24-h creatinine clearance and plasma creatinine
      for estimation of glomerular filtration rate 3 months after kidney
      transplantation.

PMID- 10926913
TI  - Compiled by david E. Bruns, editor (dbruns@aacc.org)

PMID- 10926912
TI  - Falsely increased values for rabbit immunoglobulin-based nephelometric
      immunoassays attributable to human anti-rabbit antibodies.

PMID- 10926914
TI  - Advances in clinical laboratory hematology. The twenty-third arnold O. Beckman
      conference in clinical chemistry

PMID- 10926915
TI  - The CBC at the turn of the millennium: an overview.
AB  - This review offers a birds-eye view of the state of automated hematology at the
      turn of the millennium. Despite its shortcomings (mainly flaggings and labor
      intensive demands for confirmation), instrument-driven hematology provides much
      accurate and precise data to clinicians. Advances in technology over the next few
      decades will undoubtedly improve on the categorization of currently ambiguous
      mononuclear cells and even introduce channels for the detection and
      subclassification of poikilocytes. Until then, familiarity with the morphology of
      blood cell variants will be mandatory for technologists attending to the demands
      of flagging.

PMID- 10926916
TI  - Flow cytometry: principles and clinical applications in hematology.
AB  - The use of flow cytometry in the clinical laboratory has grown substantially in
      the past decade. This is attributable in part to the development of smaller, user
      friendly, less-expensive instruments and a continuous increase in the number of
      clinical applications. Flow cytometry measures multiple characteristics of
      individual particles flowing in single file in a stream of fluid. Light
      scattering at different angles can distinguish differences in size and internal
      complexity, whereas light emitted from fluorescently labeled antibodies can
      identify a wide array of cell surface and cytoplasmic antigens. This approach
      makes flow cytometry a powerful tool for detailed analysis of complex populations
      in a short period of time. This report reviews the general principles in flow
      cytometry and selected applications of flow cytometry in the clinical hematology
      laboratory.

PMID- 10926917
TI  - Understanding and identifying monoclonal gammopathies.
AB  - Monoclonal gammopathies reflect conditions in which abnormal amounts of
      immunoglobulins are produced by a clone that developed from a single pro-B germ
      cell. The condition may reflect a disease process or be benign. The primary
      purpose of this review is to emphasize routine clinical laboratory techniques
      that currently are recommended for use in identifying monoclonal gammopathies
      from serum and urine. Selection of the preferred technique and correct
      interpretation often is dependent on an understanding of the immunological basis
      and clinical sequelae associated with these conditions. For this reason, we first
      briefly discuss the structure, production, and nature of immunoglobulins, and
      then describe important features of the associated diseases. Finally, we discuss
      strengths and weaknesses of the techniques and make reference to current
      recommendations to facilitate optimal testing. We discuss in detail high
      resolution electrophoresis, methods for quantifying immunoglobulins,
      immunofixation electrophoresis, problems associated with analysis of urine
      immunoglobulins, and identification of cryoglobulins and immune complexes.

PMID- 10926918
TI  - Bone marrow and peripheral blood hematopoietic stem cell transplantation: focus
      on autografting.
AB  - This review focuses on certain of the principles involved in high-dose
      chemotherapy and radiation therapy along with autologous hematopoietic stem cell
      transplantation for the treatment of certain malignancies. In addition, the
      evidence, wherever possible based on randomized data, for the application of this
      approach in certain malignancies is reviewed. The malignancies highlighted
      include acute myeloid leukemia, acute lymphoblastic leukemia, non-Hodgkin
      lymphoma, Hodgkin disease, and breast cancer.

PMID- 10926919
TI  - Multifaceted approach to the diagnosis and classification of acute leukemias.
AB  - Until recently, the diagnosis and classification of acute myeloid (AML) and acute
      lymphoblastic (ALL) leukemias was based almost exclusively on well-defined
      morphologic criteria and cytochemical stains. Although most cases can be
      diagnosed by these methods, there is only modest correlation between morphologic
      categories and treatment responsiveness and prognosis. The expansion of
      therapeutic options and improvement in remission induction and disease-free
      survival for both AML and ALL have stimulated emphasis on defining good and poor
      treatment response groups. This is most effectively accomplished by a
      multifaceted approach to diagnosis and classification using immunophenotyping,
      cytogenetics, and molecular analysis in addition to the traditional methods.
      Immunophenotyping is important in characterizing morphologically poorly
      differentiated acute leukemias and in defining prognostic categories of ALL.
      Cytogenetic and molecular studies provide important prognostic information and
      are becoming vitally important in determining the appropriate treatment protocol.
      With optimal application of these techniques in the diagnosis of acute leukemias,
      treatment strategies can be more specifically directed and new therapeutic
      approaches can be evaluated more effectively.

PMID- 10926920
TI  - Coagulation and bleeding disorders: review and update.
AB  - Hemostasis is initiated by injury to the vascular wall, leading to the deposition
      of platelets adhering to components of the subendothelium. Platelet adhesion
      requires the presence of von Willebrand factor and platelet receptors (IIb/IIIa
      and Ib/IX). Additional platelets are recruited to the site of injury by release
      of platelet granular contents, including ADP. The "platelet plug" is stabilized
      by interaction with fibrinogen. In this review, I consider laboratory tests used
      to evaluate coagulation, including prothrombin time, activated partial
      thromboplastin time, thrombin time, and platelet count. I discuss hereditary
      disorders of platelets and/or coagulation proteins that lead to clinical bleeding
      as well as acquired disorders, including disseminated intravascular coagulation
      and acquired circulating anticoagulants.

PMID- 10926921
TI  - Transfusion medicine: an overview and update.
AB  - The discovery of AIDS in the 1980s and its rapid evolution as a major concern for
      physicians and their patients have led to many questions about the safety of the
      blood supply. The attention placed on AIDS has led to new discoveries and
      technologies to reduce the risk of other transfusion complications such as
      hepatitis, bacterial contamination, and transfusion-associated graft-vs-host
      disease. Concerns about blood safety have focused much attention on alternative
      blood transfusion strategies such as autologous blood, viral inactivation, and
      artificial blood substitutes. This review describes the transfusion medicine
      delivery system in the United States, with special emphasis on evolving
      developments and their implications for the discipline of chemical pathology.

PMID- 10926922
TI  - Cobalamin and folate evaluation: measurement of methylmalonic acid and
      homocysteine vs vitamin B(12) and folate.
AB  - Vitamin B(12) and folate are two vitamins that have interdependent roles in
      nucleic acid synthesis. Deficiencies of either vitamin can cause megaloblastic
      anemia; however, inappropriate treatment of B(12) deficiency with folate can
      cause irreversible nerve degeneration. Inadequate folate nutrition during early
      pregnancy can cause neural tube defects in the developing fetus. In addition,
      folate and vitamin B(12) deficiency and the compensatory increase in homocysteine
      are a significant risk factor for cardiovascular disease. Laboratory support for
      the diagnosis and management of these multiple clinical entities is controversial
      and somewhat problematic. Automated ligand binding measurements of vitamin B(12)
      and folate are easiest to perform and widely used. Unfortunately, these tests are
      not the most sensitive indicators of disease. Measurement of red cell folate is
      less dependent on dietary fluctuations, but these measurements may not be
      reliable. Homocysteine and methylmalonic acid are better metabolic indicators of
      deficiencies at the tissue level. There are no "gold standards" for the diagnosis
      of these disorders, and controversy exists regarding the best diagnostic
      approach. Healthcare strategies that consider the impact of laboratory tests on
      the overall costs and quality of care should consider the advantages of including
      methylmalonic acid and homocysteine in the early evaluation of patients with
      suspected deficiencies of vitamin B(12) and folate.

PMID- 10926923
TI  - Laboratory investigation of hemoglobinopathies and thalassemias: review and
      update.
AB  - Structural hemoglobin (Hb) variants typically are based on a point mutation in a
      globin gene that produce a single amino acid substitution in a globin chain.
      Although most are of limited clinical significance, a few important subtypes have
      been identified with some frequency. Homozygous Hb C and Hb S (sickle cell
      disease) produce significant clinical manifestations, whereas Hb E and Hb D
      homozygotes may be mildly symptomatic. Although heterozygotes for these variants
      are typically asymptomatic, diagnosis may be important for genetic counseling.
      Thalassemia, in contrast, results from quantitative reductions in globin chain
      synthesis. Those with diminished beta-globin chains are termed beta-thalassemias,
      whereas those with decreased alpha-chain production are called alpha
      thalassemias. Severity of clinical manifestations in these disorders relates to
      the amount of globin chain produced and the stability of residual chains present
      in excess. The thalassemia minor syndromes are characterized clinically by mild
      anemia with persistent microcytosis. Thalassemia intermedia (i.e., Hb H disease)
      is typified by a moderate, variably compensated hemolytic anemia that may present
      with clinical symptoms during a period of physiologic stress such as infection,
      pregnancy, or surgery. The thalassemia major syndromes produce severe, life
      threatening anemia. alpha-Thalassemia major usually is incompatible with
      extrauterine life; beta-thalassemia major presents in infancy and requires life
      long transfusion therapy and/or bone marrow transplantation for successful
      control of the disease. Double heterozygosity for certain structural variants
      and/or thalassemia syndromes may also lead to severe clinical disease. Several
      guidelines have been published that outline the required steps for
      hemoglobinopathy and thalassemia investigation. The availability of HPLC has
      streamlined many of these requirements, allowing an efficient stepwise diagnostic
      strategy for these complex disorders.

PMID- 10926924
TI  - Activation of extracellular signal-regulated kinase 1/2 inhibits type I collagen
      expression by human skin fibroblasts.
AB  - Treatment with the lipid second messenger, ceramide, activates extracellular
      signal-regulated kinase-1/2 (ERK1/2), c-Jun N-terminal kinase, and p38 in human
      skin fibroblasts and induces their collagenase-1 expression (Reunanen, N.,
      Westermarck, J., Hakkinen, L., Holmstrom, T. H., Elo, I., Eriksson, J. E., and
      Kahari, V.-M. (1998) J. Biol. Chem. 273, 5137-5145). Here we show that C(2)
      ceramide inhibits expression of type I and III collagen mRNAs in dermal
      fibroblasts, suppresses proalpha2(I) collagen promoter activity, and reduces
      stability of type I collagen mRNAs. The down-regulatory effect of C(2)-ceramide
      on type I collagen mRNA levels was abrogated by protein kinase C inhibitors H7,
      staurosporine, and Ro-31-8220 and potently inhibited by a combination of MEK1,2
      inhibitor PD98059 and p38 inhibitor SB203580. Activation of ERK1/2 by adenovirus
      mediated expression of constitutively active MEK1 resulted in marked down
      regulation of type I collagen mRNA levels and production in fibroblasts, whereas
      activation of p38 by constitutively active MAPK kinase-3b and MAPK kinase-6b
      slightly up-regulated type I collagen expression. These results identify the
      ERK1/2 signaling cascade as a potent negative regulatory pathway with respect to
      type I collagen expression in fibroblasts, suggesting that it mediates inhibition
      of collagen production in response to mitogenic stimulation and transformation.

PMID- 10926925
TI  - Inhibition of Akt and its anti-apoptotic activities by tumor necrosis factor
      induced protein kinase C-related kinase 2 (PRK2) cleavage.
AB  - Akt is stimulated by several growth factors and has a major anti-apoptotic role
      in the cell. Therefore, we hypothesized that a pathway leading to the inhibition
      of Akt might be utilized in the process of apoptosis. Accordingly, we used a
      yeast two-hybrid screening assay to identify the proteins that interact with and
      possibly inhibit Akt. We found that the C-terminal region of protein kinase C
      related kinase 2 (PRK2), containing amino acids 862 to 908, specifically binds to
      Akt in yeast and mammalian cells. During early stages of apoptosis, the C
      terminal region of PRK2 is cleaved from the inhibitory N-terminal region and can
      bind Akt. The protein-protein interaction between Akt and the PRK2 C-terminal
      region specifically down-modulates the protein kinase activities of Akt by
      inhibiting phosphorylation at threonine 308 and serine 473 of Akt. This
      inhibition of Akt leads to the inhibition of the downstream signaling of Akt in
      vivo. The PRK2 C-terminal fragment strongly inhibits the Akt-mediated
      phosphorylation of BAD, a pro-apoptotic Bcl-2 family protein, and blocks the anti
      apoptotic activities of Akt in vivo. These results provide direct evidence that
      the products of protein cleavage during apoptosis inhibit pro-survival
      signalings, leading to the amplification of pro-apoptotic signalings in the cell.

PMID- 10926927
TI  - Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by
      arresting the G protein activation switch.
AB  - Signaling by D(2)-dopamine receptors in neurons likely proceeds in the presence
      of Ca(2+) oscillations. We describe here the biochemical basis for a cross-talk
      between intracellular Ca(2+) and the D(2) receptor. By activation of calmodulin
      (CaM), Ca(2+) directly inhibits the D(2) receptor; this conclusion is based on
      the following observations: (i) The receptor contains a CaM-binding motif in the
      NH(2)-terminal end of the third loop, a domain involved in activating G(i/o). A
      peptide fragment encompassing this domain (D2N) bound dansylated CaM in a Ca(2+)
      dependent manner (K(D) approximately 0.1 micrometer). (ii) Activation of purified
      Galpha(i1) by D2N, and D(2) receptor-promoted GTPgammaS (guanosine 5'-(3-O
      thio)triphosphate) binding in membranes was suppressed by Ca(2+)/CaM (IC(50)
      approximately 0.1 micrometer). (iii) If Ca(2+) influx was elicited in D(2)
      receptor-expressing HEK293 cells, agonist-dependent inhibition of cAMP formation
      decreased. This effect was not seen with other G(i)-coupled receptors (A(1)
      adenosine and Mel(1A)-melatonin receptor). (iv) The D(2) receptor was retained by
      immobilized CaM and radiolabeled CaM was co-immunoprecipitated with the receptor.
      Specifically, inhibition by CaM does not result from uncoupling the D(2) receptor
      from its cognate G protein(s); rather, CaM directly targets the D(2) receptor to
      block the receptor-operated G protein activation switch.

PMID- 10926928
TI  - Inhibitory effects of MLDG-containing heterodimeric disintegrins reveal distinct
      structural requirements for interaction of the integrin alpha 9beta 1 with VCAM
      1, tenascin-C, and osteopontin.
AB  - The integrin alpha9beta1 is expressed on epithelial cells, smooth muscle cells,
      skeletal muscle, and neutrophils and recognizes at least three distinct ligands:
      vascular cell adhesion molecule 1 (VCAM-1), tenascin-C, and osteopontin. The
      alpha9 subunit is structurally similar to the integrin alpha4 subunit, and
      alpha9beta1 and alpha4beta1 both recognize VCAM-1 as a ligand. We therefore
      examined whether the disintegrin EC3, which we have recently shown specifically
      inhibits the binding of alpha4 integrins to ligands, would also be a functional
      inhibitor of alpha9beta1. EC3 and a novel heterodimeric disintegrin that we
      identified, EC6, both were potent inhibitors of alpha9beta1-mediated adhesion to
      VCAM-1 and of neutrophil migration across tumor necrosis factor-activated
      endothelial cells. A peptide containing a novel MLDG motif shared by both of
      these disintegrins also inhibited alpha9beta1- and alpha4beta1-mediated adhesion
      to VCAM-1. Surprisingly though, concentrations of EC3 that completely inhibited
      adhesion of alpha9-transfected cells to VCAM-1 had little or no effect on
      adhesion to either of the other alpha9beta1 ligands, osteopontin and tenascin-C.
      Furthermore, peptides AEIDGIEL and SVVYGLR, which we have previously shown
      inhibit binding of alpha9beta1-expressing cells to tenascin-C and osteopontin,
      respectively, had no effect on adhesion to VCAM-1. These data suggest that there
      are structurally distinct requirements for interactions of the alpha9beta1
      integrin with VCAM-1 and the extracellular matrix ligands osteopontin and
      tenascin-C.

PMID- 10926929
TI  - Regulation of expression of phospholipase D1 and D2 by PEA-15, a novel protein
      that interacts with them.
AB  - Phospholipase D (PLD), a signal-transducing membrane-associated enzyme, is
      implicated in diverse processes including apoptosis, ERK activation, and glucose
      transport. Prior studies have identified specific PLD activators and repressors
      that directly regulate its enzymatic activity. Using two-hybrid screens, we have
      identified PEA-15 as a PLD interactor that unexpectedly functions to alter its
      level of expression. PEA-15 is a widely expressed death effector domain
      containing phosphoprotein involved in signal transduction, apoptosis, ERK
      activation, and glucose transport. The PLD1-interacting site on PEA-15 consists
      of part of the death effector domain domain plus additional C-terminal flanking
      sequences, whereas the PEA-15-interacting site on PLD1 overlaps the previously
      identified RhoA-interacting site. PEA-15 did not affect basal or stimulated in
      vitro PLD1 enzymatic activation. However, co-expression of PEA-15 increased
      levels of PLD1 activity. This increased activation correlated with higher PLD1
      protein expression levels, as marked by faster accumulation and longer
      persistence of PLD1 when PEA-15 was present. PEA-15 similarly increased protein
      expressions level of PLD2 and co-immunoprecipitated with it. These results
      suggest that PEA-15 may stabilize PLD or act as a PLD chaperone. The common
      involvement of PEA-15 and PLD in apoptosis, ERK activation, and glucose transport
      additionally suggests functional significance.

PMID- 10926930
TI  - Engagement of the CrkL adapter in interleukin-5 signaling in eosinophils.
AB  - Interleukin-5 (IL-5) drives the terminal differentiation of myeloid progenitors
      to the eosinophil lineage; blocks eosinophil apoptosis; and primes eosinophils
      for enhanced functional activities in allergic, parasitic, and other eosinophil
      associated diseases. Here we describe a novel signaling pathway activated by the
      IL-5 receptor in eosinophils involving the CrkL adapter protein. We determined
      whether IL-5 induces activation of CrkL and STAT5 in eosinophils using both the
      human eosinophil-differentiated AML14.3D10 cell line and purified peripheral
      blood eosinophils from normal donors. Stimulation of AML14.3D10 cells or blood
      eosinophils with IL-5 induced rapid tyrosine phosphorylation of the CrkL adapter
      and STAT5 and the association of CrkL and STAT5 in vivo as evidenced by the
      detection of STAT5 in anti-CrkL immunoprecipitates. The resulting CrkL.STAT5
      complexes translocated to the nucleus and bound STAT5 consensus DNA-binding sites
      present in the promoters of IL-5-regulated genes, as shown in gel mobility and
      antibody supershift assays. IL-5 also induced marked activity of an 8X-GAS
      (interferon gamma-activated site)-luciferase reporter construct in transient
      transfections of AML14.3D10 eosinophils, demonstrating that these complexes play
      a functional role in IL-5 signaling. CrkL was also found to interact, via its N
      terminal SH3 domain, with C3G, a guanine exchange factor for the small G-protein
      Rap1, which was also rapidly activated in an IL-5-dependent manner in these
      cells, establishing that CrkL mediates downstream activation of at least two
      signaling cascades in IL-5-stimulated eosinophils. Thus, the CrkL adapter plays
      an important role in IL-5 signaling in the eosinophil, acting as a nuclear
      adapter for STAT5 and as an upstream regulator of the C3G-Rap1 signaling pathway.

PMID- 10926931
TI  - Processing, stability, and receptor binding properties of oligomeric envelope
      glycoprotein from a primary HIV-1 isolate.
AB  - The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) is
      thought to exist on the virion surface as a trimer of non-covalently associated
      gp120/gp41 molecules. We expressed trimeric envelope glycoprotein from three
      primary, macrophage tropic HIV-1 isolates in baby hamster kidney cells and
      analyzed the furin-mediated cleavage, stability, and receptor binding properties
      of the oligomers. The envelope glycoprotein was secreted in a soluble form
      deleted of its transmembrane anchor and the intracytoplasmic domain (gp140). A
      mixture of trimers, dimers, and monomers of gp140 as well as monomeric gp120 was
      detected on polyacrylamide gels. Analysis by sucrose gradient centrifugation
      revealed that trimers and dimers were essentially composed of uncleaved gp140,
      whereas most of the gp120 was found in the monomeric fraction. To analyze the
      effect of the cleavage of gp140 to gp120/Delta41 on trimerization, we co
      expressed the furin protease along with gp140. Surprisingly, furin expression
      changed the subcellular localization of the envelope glycoprotein, which became
      in majority sequestered in the major furin compartment, the trans-Golgi network,
      as judged by confocal laser microscopy. The envelope glycoprotein secreted from
      furin-co-expressing cells was almost completely cleaved to gp120 and Deltagp41,
      but gp120 was found exclusively in the monomeric fraction, with a few residual
      oligomers being composed of uncleaved gp140. Secreted uncleaved gp140 trimers
      were purified to homogeneity and analyzed for their capacity to interact with
      cellular receptors CD4 and CC chemokine receptor 5 (CCR5). Receptor binding was
      analyzed on CD4- and CCR5-expressing cells as well as on peripheral blood
      mononuclear cells. Trimers showed greatly reduced binding to CD4 as compared with
      monomers. Neither monomers nor trimers bound directly to CCR5. In conclusion, our
      results show that the cleaved form of the envelope glycoprotein does not form
      stable trimers, suggesting that gp120/gp41 oligomers on the virion surface might
      be stabilized by a yet to be identified mechanism and that the virion might
      attach to CD4 via a monomeric form of gp120. These results are relevant to the
      development of an envelope-based vaccine against AIDS.

PMID- 10926932
TI  - Mutation of arginine 44 of GAT-1, a (Na(+) + Cl(-))-coupled gamma-aminobutyric
      acid transporter from rat brain, impairs net flux but not exchange.
AB  - The gamma-aminobutyric acid (GABA) transporter GAT-1 is a prototype of a large
      family of neurotransmitter transporters that includes those of dopamine and
      serotonin. GAT-1 maintains low synaptic concentrations of neurotransmitter by
      coupling GABA uptake to the fluxes of sodium and chloride. Here we identify a
      stretch of four amino acid residues predicted to lie in the juxtamembrane region
      prior to transmembrane domain 1 in the cytoplasmic amino-terminal tail of GAT-1,
      which is critical for its function. Two residues, arginine 44 and tryptophan 47,
      are fully conserved within the transporter family, and their deletion abolishes
      GABA transport in the HeLa cell expression system used. Tryptophan 47 can be
      replaced only by aromatic residues without loss of activity. Arginine 44 is
      essential for activity. Only when it is replaced by lysine, low activity levels
      (around 15% of those of the wild type) are observed. Using a reconstitution
      assay, we show that mutants in which this residue is replaced by lysine or
      histidine exhibit sodium- and chloride-dependent GABA exchange similar to the
      wild type. This indicates that these mutants are selectively impaired in the
      reorientation of the unloaded transporter, a step in the translocation cycle by
      which net flux and exchange differ. The high degree of conservation in the
      consensus sequence RXXW suggests that this region may influence the reorientation
      step in related transporters as well.

PMID- 10926933
TI  - An extended conformation of calmodulin induces interactions between the
      structural domains of adenylyl cyclase from Bacillus anthracis to promote
      catalysis.
AB  - The edema factor exotoxin produced by Bacillus anthracis is an adenylyl cyclase
      that is activated by calmodulin (CaM) at resting state calcium concentrations in
      infected cells. A C-terminal 60-kDa fragment corresponding to the catalytic
      domain of edema factor (EF3) was cloned, overexpressed in Escherichia coli, and
      purified. The N-terminal 43-kDa domain (EF3-N) of EF3, the sole domain of edema
      factor homologous to adenylyl cyclases from Bordetella pertussis and Pseudomonas
      aeruginosa, is highly resistant to protease digestion. The C-terminal 160-amino
      acid domain (EF3-C) of EF3 is sensitive to proteolysis in the absence of CaM. The
      addition of CaM protects EF3-C from being digested by proteases. EF3-N and EF3-C
      were expressed separately, and both fragments were required to reconstitute full
      CaM-sensitive enzyme activity. Fluorescence resonance energy transfer experiments
      using a double-labeled CaM molecule were performed and indicated that CaM adopts
      an extended conformation upon binding to EF3. This contrasts sharply with the
      compact conformation adopted by CaM upon binding myosin light chain kinase and
      CaM-dependent protein kinase type II. Mutations in each of the four calcium
      binding sites of CaM were examined for their effect on EF3 activation. Sites 3
      and 4 were found critical for the activation, and neither the N- nor the C
      terminal domain of CaM alone was capable of activating EF3. A genetic screen
      probing loss-of-function mutations of EF3 and site-directed mutations based on
      the homology of the edema factor family revealed a conserved pair of aspartate
      residues and an arginine that are important for catalysis. Similar residues are
      essential for di-metal-mediated catalysis in mammalian adenylyl cyclases and a
      family of DNA polymerases and nucleotidyltransferases. This suggests that edema
      factor may utilize a similar catalytic mechanism.

PMID- 10926934
TI  - c-Crk, a substrate of the insulin-like growth factor-1 receptor tyrosine kinase,
      functions as an early signal mediator in the adipocyte differentiation process.
AB  - Differentiation of 3T3-L1 preadipocytes into adipocytes is induced by a
      combination of inducers, including a glucocorticoid, an agent that elevates
      cellular cAMP, and a ligand of the insulin-like growth factor-1 receptor.
      Previous studies have implicated protein-tyrosine phosphatase (PTPase) HA2, a
      homologue of PTPase 1B, in the signaling cascade initiated by the differentiation
      inducers. Vanadate, a potent PTPase inhibitor, blocks adipocyte differentiation
      at an early stage in the program, but has no effect on the mitotic clonal
      expansion required for differentiation. Exposure of preadipocytes to vanadate
      along with the inducing agents led to the accumulation of pp35, a phosphotyrosyl
      protein that is a substrate for PTPase HA2. pp35 was purified to homogeneity and
      shown by amino acid sequence and mass analyses of tryptic peptides to be c-Crk, a
      known cytoplasmic target of the insulin-like growth factor-1 receptor tyrosine
      kinase. Transfection of 3T3-L1 preadipocytes with a c-Crk antisense RNA
      expression vector markedly reduced c-Crk levels and prevented differentiation
      into adipocytes. Studies with C3G, a protein that binds to the SH3 domain in c
      Crk, showed that phosphorylation of c-Crk rendered the SH3 domain inaccessible to
      C3G. Taken together, these findings indicate that locking c-Crk in the
      phosphorylated state with vanadate prevents its participation in the signaling
      system that initiates adipocyte differentiation.

PMID- 10926935
TI  - GATA-1- and FOG-dependent activation of megakaryocytic alpha IIB gene expression.
AB  - FOG is a multitype zinc finger protein that is essential for megakaryopoiesis,
      binds to the amino-terminal finger of GATA-1, and modulates the transcription of
      GATA-1 target genes. Presently investigated are effects of FOG and GATA-1 on the
      transcription of the megakaryocytic integrin gene, alpha IIb. In GATA-1-deficient
      FDCER cells (in the presence of endogenous FOG), ectopically expressed GATA-1
      activated transcription 3-10-fold both from alpha IIb templates and the
      endogenous alpha IIb gene. The increased expression of FOG increased reporter
      construct transcription 30-fold overall. Unexpectedly, alphaIIb gene
      transcription also was stimulated efficiently upon the ectopic expression in of
      FOG per se. This occurred in the absence of any detectable expression of GATA-1
      and was observed in multiple independent sublines for both the endogenous alpha
      IIb gene and transfected constructs yet proved to depend largely upon conserved
      GATA elements 457 and 55 base pairs upstream from the transcriptional start site.
      In 293 cells, FOG plus GATA-1 but not FOG alone only moderately stimulated alpha
      IIb transcription, and no direct interactions of FOG with the alpha IIb promoter
      were detectable. Thus, FOG acts in concert with GATA-1 to stimulate alpha IIb
      expression but also can act via a GATA-1-independent route, which is proposed to
      involve additional hematopoietic-restricted cofactors (possibly GATA-2).

PMID- 10926936
TI  - Deposition of laminin 5 by keratinocytes regulates integrin adhesion and
      signaling.
AB  - Deposition of laminin 5 over exposed dermal collagen in epidermal wounds is an
      early event in repair of the basement membrane. We report that deposition of
      laminin 5 onto collagen switches adhesion and signaling from collagen-dependent
      to laminin 5-dependent. Ligation of laminin 5 by integrin alpha(6)beta(4)
      activates phosphoinositide 3-OH-kinase (PI3K) signaling. This activation allows
      for adhesion and spreading via integrin alpha(3)beta(1) on laminin 5 independent
      of RhoGTPase, a regulator of actin stress fibers. In contrast, adhesion and
      spreading on collagen via alpha(2)beta(1) is Rho-dependent and is inhibited by
      toxin B, a Rho inhibitor. Deposition of laminin 5 and ligation of alpha(6)beta(4)
      increases PI3K-dependent production of phosphoinositide di- and triphosphates,
      PI3K activity, and phosphorylation of downstream target protein c-Jun NH(2)
      terminal kinase. Conversely, blocking laminin 5-deposition with brefeldin A, an
      inhibitor of vesicle transport, or with anti-laminin 5 monoclonal antibodies
      abolishes the PI3K-dependent spreading mediated by alpha(3)beta(1) and
      phosphorylation of c-Jun NH(2)-terminal kinase. Studies with keratinocytes
      lacking alpha(6)beta(4) or laminin 5 confirm that deposition of laminin 5 and
      ligation by alpha(6)beta(4) are required for PI3K-dependent spreading via
      alpha(3)beta(1). We suggest that deposition of laminin 5 onto the collagen
      substratum, as in wound repair, enables human foreskin keratinocytes to interact
      via alpha(6)beta(4) and to switch from a RhoGTPase-dependent adhesion on collagen
      to a PI3K-dependent adhesion and spreading mediated by integrin alpha(3)beta(1)
      on laminin 5.

PMID- 10926937
TI  - Cerebrovascular monitoring during carotid endarterectomy.

PMID- 10926938
TI  - Intracranial hemorrhage associated with thrombolytic therapy for elderly patients
      with acute myocardial infarction: results from the Cooperative Cardiovascular
      Project.
AB  - BACKGROUND AND PURPOSE: Intracranial hemorrhage is a serious complication of
      thrombolytic therapy for acute myocardial infarction, especially among the
      elderly, but little information exists on estimating risk. Better estimation of
      risk in individual patients may allow for withholding or using alternate
      therapies among those at highest risk. METHODS: To quantify the risk and identify
      predictors of intracranial hemorrhage associated with thrombolytic therapy, we
      performed a retrospective cohort study using data from medical charts. The study
      involved nearly all acute-care hospitals in the United States. All Medicare
      patients discharged with a principal diagnosis of acute myocardial infarction
      during a 9-month period in 1994 to 1995 were included. The main outcome measure
      was intracranial hemorrhage among those treated with thrombolytic therapy.
      RESULTS: The rate of intracranial hemorrhage was 1.43% (455 of 31 732). In a
      logistic model, age > or =75 years, female, black race, prior stroke, blood
      pressure > or =160 mm Hg, tissue plasminogen activator (versus other thrombolytic
      agent), excessive anticoagulation (international normalized ratio > or =4 or
      prothrombin time > or =24), and below median weight (< or =65 kg for women; < or
      =80 kg for men) were independent predictors. A risk stratification scale was
      developed on the basis of these factors: with none or 1 of the factors (n=6651),
      the rate of intracranial hemorrhage was 0.69%; with 2 factors (n=10 509), 1.02%;
      with 3 factors (n=9074), 1.63%; with 4 factors (n=4298), 2.49%; and with > or =5
      factors (n=1071), 4. 11% (Mantel-Haenszel; P<0.001). CONCLUSIONS: The rate of
      intracranial hemorrhage in older patients after treatment with thrombolytic
      therapy exceeds 1%. Readily available factors can identify elderly patients with
      acute myocardial infarction at high and low risk for intracranial hemorrhage
      associated with thrombolytic therapy.

PMID- 10926939
TI  - Timing of recanalization after tissue plasminogen activator therapy determined by
      transcranial doppler correlates with clinical recovery from ischemic stroke.
AB  - BACKGROUND: The duration of cerebral blood flow impairment correlates with
      irreversibility of brain damage in animal models of cerebral ischemia. Our aim
      was to correlate clinical recovery from stroke with the timing of arterial
      recanalization after therapy with intravenous tissue plasminogen activator (tPA).
      METHODS: Patients with symptoms of cerebral ischemia were treated with 0.9 mg/kg
      tPA IV within 3 hours after stroke onset (standard protocol) or with 0.6 mg/kg at
      3 to 6 hours (an experimental institutional review board-approved protocol).
      National Institutes of Health Stroke Scale (NIHSS) scores were obtained before
      treatment, at the end of tPA infusion, and at 24 hours; Rankin Scores were
      obtained at long-term follow-up. Transcranial Doppler (TCD) was used to locate
      arterial occlusion before tPA and to monitor recanalization (Marc head frame,
      Spencer Technologies; Multigon 500M, DWL MultiDop-T). Recanalization on TCD was
      determined according to previously developed criteria. RESULTS: Forty patients
      were studied (age 70+/-16 years, baseline NIHSS score 18.6+/-6.2). A tPA bolus
      was administered at 132+/-54 minutes from symptom onset. Recanalization on TCD
      was found at the mean time of 251+/-171 minutes after stroke onset: complete
      recanalization occurred in 12 (30%) patients and partial recanalization occurred
      in 16 (40%) patients (maximum observation time 360 minutes). Recanalization
      occurred within 60 minutes of tPA bolus in 75% of patients who recanalized. The
      timing of recanalization inversely correlated with early improvement in the NIHSS
      scores within the next hour (polynomial curve, third order r(2)=0.429, P<0.01) as
      well as at 24 hours. Complete recanalization was common in patients who had
      follow-up Rankin Scores if 0 to 1 (P=0.006). No patients had early complete
      recovery if an occlusion persisted for >300 minutes. CONCLUSIONS: The timing of
      arterial recanalization after tPA therapy as determined with TCD correlates with
      clinical recovery from stroke and demonstrates a 300-minute window to achieve
      early complete recovery. These data parallel findings in animal models of
      cerebral ischemia and confirm the relevance of these models in the prediction of
      response to reperfusion therapy.

PMID- 10926940
TI  - Association of intraoperative transcranial doppler monitoring variables with
      stroke from carotid endarterectomy.
AB  - BACKGROUND AND PURPOSE: The outcomes of carotid endarterectomy (CEA) are, in
      addition to patient baseline characteristics, highly dependent on the safety of
      the surgical procedure. During the successive stages of the operation,
      transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) was
      used to assess the association of cerebral microembolism and hemodynamic changes
      with stroke and stroke-related death. METHODS: By use of data pooled from 2
      hospitals in the United States and the Netherlands, including 1058 patients who
      underwent CEA, the association of various TCD emboli and velocity variables with
      operative stroke and stroke-related death was evaluated by univariable and
      multivariable logistic regression analyses in combination with receiver operating
      characteristic (ROC) curve analyses. The impact of basic patient characteristics,
      such as age, sex, preoperative cerebral symptoms, and ipsilateral and
      contralateral internal carotid artery stenosis, on the prediction of operative
      stroke was also evaluated. RESULTS: We observed 31 patients with ischemic and 8
      patients with hemorrhagic operative strokes. Four of these patients died. Emboli
      during dissection (odds ratio [OR] 1.5, 95% CI 0.8 to 2.9) and wound closure (OR
      2.3, 95% CI 1.2 to 4.4) as well as > or =90% decrease of MCA peak systolic
      velocity at cross-clamping (OR 3.3, 95% CI 1.3 to 8.5) and > or =100% increase of
      the pulsatility index of the Doppler signal at clamp release (OR 7.1, 95% CI 1.4
      to 35.7) were independently associated with stroke. The ROC area of this model
      was 0.69. Of the patient characteristics, only preoperative cerebral ischemia (OR
      1.9, 95% CI 1.0 to 3.7) and > or =70% ipsilateral internal carotid artery
      stenosis (OR 0.5, 95% CI 0.2 to 0.9) were associated with stroke. Adding these
      patient characteristics to the model, the area under the ROC curve increased to
      0.73. CONCLUSIONS: In CEA, TCD-detected microemboli during dissection and wound
      closure, > or =90% MCA velocity decrease at cross-clamping, and > or =100%
      pulsatility index increase at clamp release are associated with operative stroke.
      In combination with the presence of preoperative cerebral symptoms and > or =70%
      ipsilateral internal carotid artery stenosis, these 4 TCD monitoring variables
      reasonably discriminate between patients with and without operative stroke. This
      supports the use of TCD as a potential intraoperative monitoring modality to
      alter the surgical technique by enhancing a decrease of the risk of stroke during
      or immediately after the operation.

PMID- 10926941
TI  - Silent cerebral ischemia detected by diffusion-weighted MRI after carotid
      endarterectomy.
AB  - BACKGROUND AND PURPOSE: Small emboli arising from a friable plaque during carotid
      endarterectomy (CEA) constitute an important risk of perioperative ischemic
      complications. To evaluate the incidence and significance of silent cerebral
      ischemic lesions of embolic origin after CEA, we prospectively examined a series
      of surgical patients with high-grade carotid stenosis by using diffusion-weighted
      MRI (DWI). We also tried to correlate postoperative ischemic lesions with the
      occurrence of sonographic cerebral embolic signals, the presence of plaque
      ulcerations, and the use of intraoperative shunting. METHODS: Of a consecutive
      series of 53 patients undergoing elective CEA for high-grade carotid stenosis, 48
      patients with unchanged postoperative neurological status were prospectively
      studied with DWI of the brain the day before and the day after the operation. The
      magnetic resonance images were analyzed by 2 neuroradiologists blinded to the
      clinical result of the operation. Any new hyperintense signal was interpreted as
      a postoperative ischemic lesion. RESULTS: Forty-six (95.8%) of 48 patients had
      unchanged postoperative brain DWI. In 2 patients (4.2%), a new single
      asymptomatic hyperintense signal was observed on the side of the operation. Both
      lesions were small and presumably of embolic origin. They were not related to
      sonographic embolic signals, plaque ulcerations, or intraoperative shunting.
      CONCLUSIONS: These results suggest that the incidence of silent ischemic brain
      lesions of embolic origin after CEA is low and does not correlate with the
      occurrence of intraoperative sonographic microemboli. They confirm that CEA is a
      safe procedure that carries a low risk of postoperative cerebral events.

PMID- 10926942
TI  - Fluoxetine in early poststroke depression: a double-blind placebo-controlled
      study.
AB  - BACKGROUND AND PURPOSE: Early poststroke depression (PSD) is a frequent and
      specific entity that impairs the rehabilitation and functional recovery of
      hemiplegic patients. This trial was designed to study the efficacy and tolerance
      of fluoxetine (FLX) in the treatment of early PSD. METHODS: This was a
      multicenter, double-blind, placebo-controlled study. Recent hemiplegic patients
      (<3 months) suffering from major depressive disorder (determined by International
      Classification of Diseases, 10th Revision, and Montgomery-Asberg Depression
      Rating Scale [MADRS] >19) were randomized to receive either 20 mg/d fluoxetine
      (FLX) or placebo for 6 weeks. Patients were evaluated by use of the Motricity
      Index, Mini-Mental State Examination, Functional Independence Measure, and MADRS.
      Statistical analysis was performed by using an intent-to-treat approach comparing
      the 2 groups at day 0 (baseline) and days 15, 30, and 45 (end point). RESULTS: Of
      121 patients screened, 31 were included in the study, 16 in the FLX group and 15
      in the placebo group. There were no significant differences in baseline
      characteristics among the 2 groups. The FLX-treated patients compared with
      placebo-treated patients demonstrated significant improvement in mean MADRS
      scores at end point (11.8+/-6. 7 [mean+/-SD] versus 18.7+/-10.0, respectively;
      P=0.05). FLX-treated patients compared with placebo-treated patients also
      demonstrated greater response rate (62.5% versus 33.3%, respectively) and greater
      mean decrease of MADRS (16.6 versus 8.4, respectively; P=0.02). There were no
      differences in motor, cognitive, or functional improvement and no significant
      side effects after FLX treatment, except for a patient with a moderate and
      transient increase of transaminases. CONCLUSIONS: FLX is an efficacious and well
      tolerated treatment for early PSD. Further research is needed to evaluate the
      efficacy and safety of long-term treatment in this population.

PMID- 10926943
TI  - Sex differences and similarities in the management and outcome of stroke
      patients.
AB  - BACKGROUND AND PURPOSE: Previous studies have documented sex differences in the
      management and outcome of patients with cardiovascular disease. However, little
      data exist on whether similar sex differences exist in stroke patients. We
      conducted a study to determine whether sex differences exist in patients with
      acute stroke admitted to Ontario hospitals. METHODS: Using linked administrative
      databases, we performed a population-based cohort study. The databases contained
      information on all 44 832 patients discharged from acute-care hospitals in
      Ontario between April 1993 and March 1996 with a most responsible diagnosis of
      acute stroke. The main outcomes measured consisted of sex differences in
      comorbidities, the use of rehabilitative services, the use of antiplatelet
      therapy and anticoagulants (in elderly stroke survivors aged > or =65 years
      only), discharge destination, and mortality. RESULTS: Male stroke patients were
      more likely than female stroke patients to have a history of ischemic heart
      disease (18.1% versus 15.3%, respectively; P<0.001) and diabetes mellitus (20.1%
      versus 18. 7%, respectively; P<0.001), whereas female patients were more likely
      than male patients to have hypertension (33.8% versus 30.0%, respectively;
      P<0.001) and atrial fibrillation (12.9% versus 10.2%, respectively; P<0.001).
      There were no sex differences in the usage of in-hospital rehabilitative
      services. The overall 90-day postdischarge use of aspirin and ticlopidine was
      similar in stroke survivors aged 65 to 84 years. However, among stroke survivors
      aged > or =85 years, men were more likely than women to receive aspirin (36. 0%
      versus 30.7%, respectively; P<0.001) and ticlopidine (9.2% versus 6.8%,
      respectively; P=0.007). Use of warfarin was similar for the two sexes. Men were
      more likely than women to be discharged home (50. 6% versus 40.9%, respectively;
      P<0.001) and less likely to be discharged to chronic care facilities (16.8%
      versus 25.2%, respectively; P<0.001). The risk of death 1 year after stroke was
      somewhat lower in women than men (adjusted odds ratio 0.939, 95% CI 0.899 to
      0.980; P=0.004). The mortality differences were greatest among elderly stroke
      patients. CONCLUSIONS: Elderly men are more likely than elderly women to receive
      aspirin and ticlopidine and equally like to receive warfarin after a stroke.
      Despite these differences, elderly women have a better 1-year survival after a
      stroke.

PMID- 10926944
TI  - Vascular cell components of the medullary arteries in Binswanger's disease
      brains: a morphometric and immunoelectron microscopic study.
AB  - BACKGROUND AND PURPOSE: It has been hypothesized that fibrohyalinosis of the
      medullary arteries may cause white matter lesions in Binswanger's disease (BD).
      However, previous reports have been inconsistent on the pathological alterations
      of the cellular components, which may vary in terms of vessel sizes. We therefore
      quantitatively examined vasculopathy in the medullary arteries of a defined
      caliber in BD brains with a quantitative technique. METHODS: A total of 20 brains
      were examined: 10 from patients with BD and 10 from age-matched nonneurological
      control patients. The alterations in the vascular cell components were examined
      with quantitative immunohistochemistry and immunoelectron microscopy for collagen
      and smooth muscle actin. RESULTS: The nonneurological control patients showed no
      white matter lesions. In contrast, the patients with BD invariably had marked
      white matter lesions, as well as fibrohyalinosis of the medullary arteries. The
      ratio of the area immunolabeled for collagen type I and type IV to the cross
      sectional area was 2-fold higher in the BD patients than in the control patients,
      regardless of the vessel caliber (P<0.005). Although the ratio for smooth muscle
      actin in the BD brains was increased in arteries of <100 microm (P<0.0001), there
      was no corresponding increase in the arteries of >100 microm. However, in the
      ultrastructure of these vessels, the cell bodies immunolabeled for smooth muscle
      actin were hypertrophic and segregated from each other by proliferated fibrils.
      The basal lamina appeared multilayered, and the endothelial cells were swollen.
      Collagen type I and type IV immunoreactive fibrils also proliferated in the
      pericapillary space of the BD brains. CONCLUSIONS: The proliferation of collagen
      fibrils in the media and adventitia of the blood vessels in BD brains was not
      specific to small arteries and arterioles but also occurred in the pericapillary
      spaces. Pericapillary sclerosis, smooth muscle cell proliferation in the terminal
      arterioles, and their morphological transformation in the proximal arteries may
      alter the shear rates and thus cause profound microcirculatory disturbances in BD
      brains.

PMID- 10926945
TI  - Epidemiology of aneurysmal subarachnoid hemorrhage in Australia and New Zealand:
      incidence and case fatality from the Australasian Cooperative Research on
      Subarachnoid Hemorrhage Study (ACROSS).
AB  - BACKGROUND AND PURPOSE: More data on the epidemiology of subarachnoid hemorrhage
      (SAH) are required to increase our understanding of etiology and prevention. This
      study sought to determine the incidence and case fatality of SAH from 4
      prospective, population-based registers in Australia and New Zealand. METHODS: We
      identified all cases of "aneurysmal" SAH from November 1995 to June 1998 in
      Adelaide, Hobart, Perth (Australia), and Auckland (New Zealand), a total
      population of approximately 2.8 million, using standard diagnostic criteria and
      uniform community-wide surveillance and data extraction procedures. RESULTS: A
      total of 436 cases of SAH were registered, including 432 first-ever events and 4
      recurrent events. The mean age of cases was 57 years (range, 16 to 94 years), and
      62% were female. From the 400 first-ever events registered over whole years, the
      crude annual incidence for the total population was 8.1 per 100 000 (95% CI, 7.4,
      9.0), with rates higher for females (9. 7; 95% CI, 8.6, 11.0) than for males
      (6.5; 95% CI, 5.5, 7.6). Age-specific rates showed a continuous upward trend with
      age, although the shape and strength of this association differed between the
      sexes. Standardized annual incidence of SAH varied across centers, being highest
      in Auckland largely because of the high rate in Maori and Pacific people. The 28
      day case fatality rate for the total population was 39% (95% CI, 34%, 44%), with
      little variation in ratios across centers. CONCLUSIONS: There is variation in the
      incidence of SAH in Australia and New Zealand, but the rates are consistently
      higher for females. A monotonic increase in incidence with age suggests that
      exposures with cumulative effects and long induction times may be less relevant
      in the etiology of SAH.

PMID- 10926946
TI  - Serum gamma-glutamyl transferase, self-reported alcohol drinking, and the risk of
      stroke.
AB  - BACKGROUND AND PURPOSE: There is still conflicting evidence regarding a link
      between alcohol drinking and the risk of stroke. In most prospective studies, the
      assessment of the alcohol drinking has been based on self-reporting, which may be
      unreliable. The aim of the present study was to examine the relationship between
      stroke and both the self-reported alcohol drinking and the serum gamma-glutamyl
      transferase (GGT) concentration, which was regarded as a biological marker of
      alcohol drinking. METHODS: A prospective cohort study of 14 874 Finnish men and
      women aged 25 to 64 years who participated in a cardiovascular risk-factor survey
      in 1982 or 1987. The following risk factors, determined at baseline, were
      included in data analyses: self-reported alcohol drinking, GGT, smoking, blood
      pressure, serum cholesterol, and body mass index. The cohorts were followed until
      the end of 1994. Stroke events were identified through the national death
      registry and hospital discharge registry by computerized record linkage. RESULTS:
      Serum GGT concentration was associated with the risk of total and ischemic stroke
      in both genders. There was also a significant association among men between GGT
      and the risk of intracerebral hemorrhage and among women between GGT and the risk
      of subarachnoid hemorrhage. The relationships remained statistically significant
      also after adjustment for other risk factors. Self-reported alcohol drinking did
      not associate with any type of stroke. CONCLUSIONS: These results support the
      hypothesis that excessive alcohol drinking is related to an increased risk of
      stroke. Biological markers of alcohol drinking, such as serum GGT level, are
      useful for the assessment of risks related to alcohol drinking.

PMID- 10926947
TI  - Hemostatic markers in patients at risk of cerebral ischemia.
AB  - BACKGROUND: Increased levels of markers of hemostasis may assist in the
      determination of the extent of carotid occlusive disease and the identification
      of neurologically intact individuals at increased risk of ischemic events.
      METHODS: We conducted a prospective study of 304 subjects, including 82 with a
      recent (< or =7 days) transient ischemic attack (TIA), 157 asymptomatic
      individuals with a cervical bruit, and 65 control subjects. Baseline evaluation
      included a neurological assessment, ECG, cervical ultrasonography, and cerebral
      CT and/or MRI. Levels of markers of coagulation and fibrinolytic activity were
      also determined. Results were analyzed in relation to the degree of carotid
      disease and the subsequent occurrence of cerebral and cardiac ischemic events.
      RESULTS: Over a mean follow-up period of 2.8 years (SD, 1.3 years), 114 ischemic
      events occurred. Survival analyses showed that prothrombin fragment 1.2 (F(1.2))
      was a predictor of time to cerebral and cardiac ischemic events in the combined
      TIA and asymptomatic bruit group (relative risk [RR], 1.46; 95% CI, 1.18 to 1.81)
      as well as in the asymptomatic bruit group separately (RR, 1.70; 95% CI, 1.14 to
      2.53). In the TIA group, both F(1.2) (RR, 2.36; 95% CI, 1.19 to 4.68) and severe
      (> or =80%) carotid stenosis (RR, 3.53; 95% CI, 1.19 to 10.51) were predictive of
      time to ischemic stroke, myocardial infarction, or vascular death. CONCLUSIONS:
      In patients with TIAs and in asymptomatic individuals with cervical bruits,
      F(1.2) levels were found to be independent predictors of subsequent cerebral and
      cardiac ischemic events. Our results are consistent with an active role of the
      coagulation system through upregulation of thrombin in carotid disease
      progression and in the pathogenesis of ischemic events in patients at risk.

PMID- 10926948
TI  - Serial measurement of vascular endothelial growth factor and transforming growth
      factor-beta1 in serum of patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Both vascular endothelial growth factor (VEGF) and
      transforming growth factor-beta1 (TGF-beta1) are expressed in higher than normal
      concentrations in the penumbra of patients after ischemic stroke. Because both
      cytokines are central to the processes of angiogenesis, tissue inflammation, and
      fibrosis, we performed serial measurements of these cytokines in patients with
      cerebral infarction and determined their relationship to stroke etiology and
      volume. METHODS: We serially (at days 0, 1, 3, 7, and 14) measured the serum
      levels of VEGF and active TGF-beta1 in 29 patients with acute ischemic stroke.
      Age-matched healthy subjects (n=26) were used as controls. RESULTS: Expression of
      VEGF was significantly increased in the majority of patients after acute stroke
      at each of the time points compared with normal controls. Highest expression
      occurred at day 7 (588+/-121 pg/mL; P=0.005), and it remained significantly
      elevated at 14 days after stroke. Expression of VEGF correlated with infarct
      volume, clinical disability (Scandinavian Stroke Scale), and peripheral
      leukocytosis and was significantly higher in patients with atherothrombotic large
      vessel disease and ischemic heart disease (P<0.05 in all cases). In contrast,
      expression of active TGF-beta1 was not significantly different from control
      patients at any of the measured time points. When the mean concentration of TGF
      beta1 from each patient (pooled time points) was compared with the control mean,
      a significant increase was found in only 2 patients, whereas levels decreased in
      12 patients (P<0.05). There was no correlation between circulating active TGF
      beta1 and VEGF expression, leukocytosis, stroke subtype, or patient disability as
      assessed by Scandinavian Stroke Scale score. CONCLUSIONS: VEGF but not TGF-beta1
      showed a dramatic increase in serum of stroke patients. Correlation between
      stroke severity and VEGF concentration suggests it could be involved in the
      subsequent repair processes resulting in partial recovery after stroke.
      Correlation between VEGF expression and peripheral leukocytosis suggests that
      these changes may also reflect the immunologic status of the patient. VEGF may
      play an important role in the pathophysiology of acute ischemic stroke and could
      be of value in future treatment strategies.

PMID- 10926949
TI  - Prediction of mortality by ultrasound screening of a general population for
      carotid stenosis: the Tromso Study.
AB  - BACKGROUND AND PURPOSE: The extensive use of ultrasound examination of carotid
      arteries has revealed stenosis in many asymptomatic subjects, and clinical
      studies have shown that carotid stenosis is a risk factor for cardiovascular
      disease and death. However, information on stenosis as detected in a general
      population and its relation to mortality is scarce. The purpose of this
      population-based study was to assess whether carotid stenosis is a predictor of
      death. METHODS: In 1994 to 1995, 248 subjects with suspected carotid stenosis
      were identified among 6727 men and women 25 to 84 years of age who were examined
      with ultrasound. These subjects and 496 age- and sex-matched control subjects
      were followed up for 4.2 years, and the number and causes of deaths were
      registered. RESULTS: The unadjusted relative risk for death was 2.72 (95% CI,
      1.57 to 4.75) for subjects with stenosis compared with control subjects.
      Adjusting for cardiovascular risk factors increased the relative risk to 3.47
      (95% CI, 1.47 to 8.19). The adjusted relative risk in persons with stenosis and
      no cardiovascular disease or diabetes was 5.66 (95% CI, 1.53 to 20.90), which was
      higher than in subjects with stenosis and self-reported disease (1.79; 95% CI,
      0.75 to 4.27). There was a dose-response relationship between degree of stenosis
      and risk of death (P=0.002 for linear trend). Carotid stenosis was a stronger
      predictor of death than self-reported cardiovascular disease or diabetes.
      CONCLUSIONS: Carotid stenosis is a strong and independent predictor of death.

PMID- 10926950
TI  - Behavioral risk factor prevalence and lifestyle change after stroke: a
      prospective study.
AB  - BACKGROUND AND PURPOSE: Stroke patients have a 15-fold increased risk of
      recurrent stroke, and those with > or =1 risk factor have a further increased
      risk of recurrence. Previous work found management of physiological risk factors
      after stroke to be unsatisfactory, but there is little information on behavioral
      risks within the stroke population. This study estimates behavioral risk factor
      prevalence after stroke and explores lifestyle change. METHODS: The study used
      data from the population-based South London Stroke Register, collected
      prospectively between 1995 and 1998. Main measures included smoking status,
      alcohol use, and obesity. Logistic regression was used to determine
      sociodemographic differences in these measures. RESULTS: At 1 year after stroke,
      22% of patients still smoked, 36% of patients were obese, and 4% drank
      excessively. Younger patients, whites, and men were more likely to smoke, and
      younger whites were more likely to drink excessively. Women and nonwhites were
      more likely to be obese. Those living in hospital, nursing home, or residential
      care and nonwhites were more likely to give up smoking, but there were no other
      associations between lifestyle change and the sociodemographic characteristics of
      patients. CONCLUSIONS: Different behavioral risk factors were associated with
      specific sociodemographic groups within the stroke population. After stroke, high
      risk groups should continue to be targeted to prevent stroke recurrence. However,
      the relationship between sociodemographic characteristics and lifestyle change
      remains unclear; more research is needed into the process of change to find out
      how best to intervene to improve secondary prevention.

PMID- 10926951
TI  - HDL-Cholesterol, total cholesterol, and the risk of stroke in middle-aged British
      men.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to examine the relation
      between serum HDL cholesterol and total cholesterol and risk of stroke. METHODS:
      We carried out a prospective study in 7735 men, 40 to 59 years of age, drawn from
      1 group practice in each of 24 British towns. Men with history of stroke were
      excluded (n=52). RESULTS: During the mean follow-up period of 16.8 years, there
      were 343 stroke cases (fatal and nonfatal) in the 7683 men with no history of
      stroke. Higher levels of HDL cholesterol were associated with a significant
      decrease in risk of stroke even after adjustment for potential confounders (top
      fifth versus lowest fifth: adjusted relative risk=0.68, 95% CI 0.46 to 0.99). The
      inverse relation was seen only for nonfatal strokes (adjusted relative risk=0.59,
      95% CI 0.39 to 0.90; top fifth versus lowest fifth). Total cholesterol showed no
      graded association with fatal strokes, but men with levels > or =8.1 mmol/L (top
      5% of the distribution) showed increased risk of nonfatal stroke, although this
      was not statistically significant after adjustment (adjusted RR=1.46, 95% CI 0.91
      to 2.32). The beneficial effects of elevated HDL cholesterol on nonfatal stroke
      were seen in both smokers and nonsmokers and were more evident in men with
      hypertension than in normotensives. In hypertensive men, elevated HDL cholesterol
      (top fifth) was associated with a significant 50% reduction in risk of nonfatal
      strokes compared with men in the lowest fifth. CONCLUSIONS: Higher levels of HDL
      cholesterol were associated with a significant decrease in risk of nonfatal
      stroke. In contrast, elevated total cholesterol showed a weak positive
      association with nonfatal strokes. The marked inverse association between HDL
      cholesterol and stroke seen in hypertensives emphasizes the importance of those
      modifiable risk factors for stroke known to lower the concentrations of HDL
      cholesterol.

PMID- 10926952
TI  - Oxidative stress in the context of acute cerebrovascular stroke.
AB  - BACKGROUND AND PURPOSE: Free radical generation and consequent oxidative stress
      in thrombotic cerebrovascular stroke have a distinctive role in the pathogenesis
      of ischemic brain injury. One of the potential injurious effects of
      homocyst(e)ine in occlusive vascular diseases is free radical generation. In the
      current study, we investigated the status of oxidant stress in the acute phase of
      thrombotic cerebrovascular stroke and the possible role of homocyst(e)ine.
      METHODS: We determined levels of plasma homocyst(e)ine, lipid peroxide, ascorbic
      acid, superoxide dismutase, and nitric oxide in 30 patients with thrombotic
      cerebrovascular stroke within 2 days of the onset of the attack as well as in 22
      healthy volunteers of comparable age and gender. RESULTS: Statistically
      significant elevation of homocyst(e)ine (P<0. 001), lipid peroxide (P<0.001), and
      nitric oxide (P<0.001) plasma levels were observed in stroke patients compared
      with healthy controls. On the other hand, the antioxidant ascorbic acid plasma
      levels were significantly lower in the patient group compared with healthy
      control subjects (P<0.001). Meanwhile, superoxide dismutase plasma levels were
      not statistically different in either groups. The study also revealed a
      significant and strong positive correlation between homocyst(e)ine and lipid
      peroxide (r=0.85, P<0.001). Ascorbic acid plasma levels were significantly
      negatively correlated with both homocyst(e)ine (r=-0.875, P<0.001) and lipid
      peroxide (r=-0.576, P<0.001). The nitric oxide level was positively correlated
      with superoxide dismutase (r=0.396, P<0.05). CONCLUSIONS: We conclude that
      hyperhomocyst(e)inemia is a possible causal factor in free radical generation
      during the acute phase of thrombotic cerebrovascular stroke. Pharmacological
      intervention could potentially be beneficial in this setting and warrants further
      evaluation.

PMID- 10926953
TI  - Comparison of risk factors for stroke incidence and stroke mortality in 20 years
      of follow-up in men and women in the Renfrew/Paisley Study in Scotland.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to relate risk factors in
      middle-aged men and women to stroke incidence (defined by having a hospital
      discharge with a main diagnosis of stroke) and compare this with the associations
      between risk factors and stroke mortality. METHODS: In the early to mid-1970s,
      when they were 45 to 64 years of age, 7052 men and 8354 women from the
      Renfrew/Paisley prospective cohort study in Scotland were screened. Risk factors
      measured included blood pressure, blood cholesterol and glucose, respiratory
      function, cardiothoracic ratio, smoking habit, height, body mass index,
      preexisting coronary heart disease, and diabetes. These were related to stroke
      incidence over 20 years of follow-up. RESULTS: Diastolic and systolic blood
      pressure, smoking, cardiothoracic ratio, preexisting coronary heart disease, and
      diabetes were positively related to stroke incidence for men and women, whereas
      adjusted FEV(1) (forced expiratory volume in 1 second) and height were negatively
      related. Cholesterol was not related to stroke. Glucose for nondiabetic subjects
      had a U-shaped relationship with stroke. Body mass index was not clearly related
      to stroke, although participants with the highest body mass index had the highest
      stroke rate. Former smokers had similar stroke rates to never-smokers. Tests
      between the associations of risk factors and stroke incidence revealed these were
      not statistically different from the associations with stroke mortality.
      CONCLUSIONS: The risk factors had a similar effect on stroke incidence as on
      stroke mortality. Epidemiological studies with information on stroke mortality
      are likely to give results applicable to stroke incidence.

PMID- 10926954
TI  - Dynamic regulation of middle cerebral artery blood flow velocity in aging and
      hypertension.
AB  - BACKGROUND AND PURPOSE: Although aging and hypertension may predispose
      hypertensive elderly subjects to cerebral hypoperfusion during orthostatic
      stress, their effects on the acute cerebral autoregulatory response to
      hypotension are not known. METHODS: Continuous middle cerebral artery blood flow
      velocity (BFV) (transcranial Doppler ultrasound) and mean arterial pressure (MAP,
      Finapres) were measured in response to (1) acute hypotension during standing, (2)
      steady-state sitting and standing, and (3) hypercarbia during CO(2) rebreathing
      in 10 healthy young subjects (age 24+/-1 years), 10 healthy elderly subjects (age
      72+/-3 years), and 10 previously treated hypertensive elderly (age 72+/-2 years)
      subjects. CO(2) reactivity was computed as the slope of cerebrovascular
      conductance (CVC=BFV/MAP) versus end-expiratory CO(2). Coherence, transfer
      magnitudes, and phases between low-frequency MAP and BFV signals were computed
      from their autospectra during 5 minutes of sitting and standing. RESULTS: MAP
      fell to a similar extent in all groups by an average of 21 to 26 mm Hg (22% to
      26%) within 30 seconds of standing. Mean BFV also fell in all subjects but
      significantly less in the older subjects (-4.7+/-0. 7 cm/s in hypertensives and 
      5.3+/-1.2 cm/s in normotensives, P=NS) compared with younger subjects (-10.1+/
      1.1 cm/s, P<0.05). CO(2) reactivity was greater in the young subjects (0.19+/
      0.01) compared with normotensive (0.14+/-0.01, P<0.05) and hypertensive elderly
      subjects (0.11+/-0.02, P<0.05) (P=NS between elderly groups). Fewer hypertensive
      subjects had coherence between MAP and BFV signals; for subjects with coherence,
      there were no significant group differences in phase or transfer magnitudes in
      either sitting or standing positions. CONCLUSIONS: Despite reduced CO(2)
      reactivity, elderly normotensive and previously treated hypertensive subjects
      retain cerebral autoregulatory capacity in response to acute orthostatic
      hypotension.

PMID- 10926955
TI  - Cerebral hemodynamics in CADASIL before and after acetazolamide challenge
      assessed with MRI bolus tracking.
AB  - BACKGROUND: White matter lesions in cerebral autosomal dominant arteriopathy with
      subcortical infarcts and leukoencephalopathy (CADASIL) are underlaid by severe
      ultrastructural changes of the arteriolar wall. Although chronic ischemia is
      presumed to cause the tissue lesions, the pattern of perfusion abnormalities and
      hemodynamic reserve in CADASIL, particularly within the white matter, remains
      unknown. METHODS: We used the MRI bolus tracking method in 15 symptomatic
      patients with CADASIL (5 with dementia) and 10 age-matched control subjects
      before and 20 minutes after the intravenous injection of acetazolamide (ACZ, 17
      mg/kg). Cerebral blood flow (CBF), blood volume (CBV), and mean transit time
      (MTT) were calculated both in the cortex and in the white matter according to the
      singular value decomposition technique. Perfusion parameters were obtained in
      regions of hyperintensities and within the normal-appearing white matter as
      observed on T2-weighted images. Analysis was performed with both absolute and
      relative (region/whole brain) values. RESULTS: A significant reduction in
      absolute and relative CBF and CBV was found within areas of T2 hyperintensities
      in white matter in the absence of significant variations of MTT. This reduction
      was more severe in demented than in nondemented patients. No significant change
      in absolute CBF and CBV values was observed in the cortex of patients with
      CADASIL. A decrease in relative CBF and CBV values was detected in the occipital
      cortex. After ACZ administration, CBF and CBV increased significantly in both the
      cortex and white matter of affected subjects, but the increase in absolute CBF
      was lower within areas of increased signal on T2-weighted images in patients than
      in the white matter of control subjects. CONCLUSIONS: In CADASIL, both basal
      perfusion and hemodynamic reserve are decreased in areas of T2 hyperintensities
      in the white matter. This hypoperfusion appears to be related to the clinical
      severity. The significant effect of ACZ on CBF and CBV suggests that cerebral
      perfusion might be increased using pharmacological vasodilation in CADASIL.

PMID- 10926956
TI  - A longitudinal study of collateral flow patterns in the circle of Willis and the
      ophthalmic artery in patients with a symptomatic internal carotid artery
      occlusion.
AB  - BACKGROUND AND PURPOSE: The purpose of the present study was to assess whether
      the direction of flow via the circle of Willis and the ophthalmic artery (OphA)
      changed over time in patients with a symptomatic occlusion of the internal
      carotid artery (ICA) who did not experience recurrent cerebral ischemic symptoms.
      METHODS: Sixty-two patients with a symptomatic ICA occlusion were investigated
      within 6 months after symptoms occurred. The investigations were repeated after 6
      and 12 months. The directions of flow in the A1 segment and the posterior
      communicating artery (PCoA), both on the side of the symptomatic ICA occlusion,
      were assessed with the use of magnetic resonance angiography. The pattern of
      collateral flow via the circle of Willis was categorized as via the A1 segment
      only, via the PCoA only, via the A1 segment plus the PCoA, or no collateral flow
      via the circle of Willis. The direction of flow in the OphA was investigated with
      transcranial Doppler sonography. CO(2) reactivity was determined with
      transcranial Doppler sonography to investigate whether changes in flow patterns
      were accompanied by changes in cerebrovascular reactivity. RESULTS: There were no
      statistically significant changes over time in the direction of blood flow in the
      A1 segment and the PCoA or in the pattern of collateral flow via the circle of
      Willis. On average, 72% of patients with a unilateral ICA occlusion (n=41) had
      willisian collateral flow compared with 37% of patients with a bilateral ICA
      occlusion (n=21; P<0.05). Patients with a unilateral ICA occlusion tended to a
      lower prevalence of reversed flow via the OphA over time. CO(2) reactivity did
      not change significantly in any patient group. In patients with a unilateral ICA
      occlusion, decreased CO(2) reactivity was associated with a higher prevalence of
      absent willisian collateral flow and a lower prevalence of collateral flow via
      the A1 segment plus the PCoA. CONCLUSIONS: The absence of recurrent cerebral
      ischemic symptoms in patients with a symptomatic ICA occlusion is not associated
      with an improvement in collateral flow via the circle of Willis or the OphA
      during 1.5-year follow-up.

PMID- 10926957
TI  - An objective characterization of atherosclerotic lesion: an alternative method to
      identify unstable plaque.
AB  - BACKGROUND AND PURPOSE: The aim of this study was to evaluate a computer-assisted
      technique to characterize atherosclerotic plaque. METHODS: In 9 subjects (7 men,
      2 women; mean age 33 years), known anatomic areas (carotid, fat, muscle,
      iliotibial tract, and tibia) were scanned with an Acuson duplex ultrasound
      machine with 72 machine settings. The ultrasound images of these anatomic areas
      were recorded on magneto-optical disks. Echo amplitude statistics were obtained,
      and the mean pixel value (MPV) was used to assess the level of echogenicity. The
      ideal settings of this particular scanner for optimal discrimination between
      these tissues types were identified by the Heuristic Index of Discrimination.
      With these settings, carotid artery scanning was performed on 17 patients (15
      men, 2 women; mean age 65 years), and the image analysis of their ultrasound
      carotid plaques was compared with their histological findings. RESULTS: In this
      study, discrimination between the selected tissues was found to be optimal when
      the controls were set at log 40 dB, 0/2/0, and gain of -5 dB. The MPV of the
      carotid specimens scanned at this setting correlated significantly with the
      histological findings (Spearman correlation, P=0.002). CONCLUSIONS: Computer
      assisted image analysis to give the MPV is a technique that may be used to
      identify unstable atherosclerotic plaques reliably.

PMID- 10926958
TI  - Activation of emergency medical services for acute stroke in a nonurban
      population: the T.L.L. Temple Foundation Stroke Project.
AB  - BACKGROUND AND PURPOSE: Activating emergency medical services (EMS) is the most
      important factor in reducing delay times to hospital arrival for stroke patients.
      Determining who calls 911 for stroke would allow more efficient targeting of
      public health initiatives. METHODS: The T.L.L. Temple Foundation Stroke Project
      is an acute stroke surveillance and intervention project in nonurban East Texas.
      Prospective case ascertainment allowed chart abstraction and structured
      interviews for all hospitalized stroke patients to determine if EMS was
      activated, and if so, by whom. RESULTS: Of 429 validated strokes, 38.0% activated
      EMS by calling 911. Logistic regression analysis comparing those who called 911
      with those who did not activate EMS found that individuals who were employed were
      81% less likely to have EMS activated (OR 0.19, 95% CI 0.04 to 0.63). Of the 163
      cases in which 911 was called, the person activating EMS was: self (patient),
      4.3%; family member of significant other, 60. 1%; paid caregiver, 18.4%; and
      coworker or other, 12.9%. Significant associations between the variables age
      group (P=0.02), insurance status (P=0.007), and living alone (P=0.05) with who
      called 911 was found on chi(2) analysis. CONCLUSIONS: Educational efforts
      directed at patients themselves at risk for stroke may be of low yield. To
      increase the use of time dependent acute stroke therapy, interventions may wish
      to concentrate on family, caregivers, and coworkers of high-risk patients. Large
      employers may be good targets to increase utilization of EMS services for acute
      stroke.

PMID- 10926959
TI  - Randomized controlled trial of integrated (managed) care pathway for stroke
      rehabilitation.
AB  - BACKGROUND AND PURPOSE: Integrated Care Pathway (ICP) is an organized, goal
      defined, and time-managed plan that has the potential of facilitating timely
      interdisciplinary coordination, improving discharge planning, and reducing length
      of hospital stay. METHODS: An ICP for stroke rehabilitation based on evidence of
      best practice, professional standards, and existing infrastructure was developed.
      Its effectiveness was tested in 152 stroke patients undergoing rehabilitation who
      were randomized to receive ICP care coordinated by an experienced nurse (n=76) or
      conventional multidisciplinary care (n=76). RESULTS: The age, sex, premorbid
      functional ability, and stroke characteristics of the 2 groups were comparable.
      There were no differences in mortality rates (10 [13%] versus 6 [8%]),
      institutionalization (10 [13%] versus 16 [21%]), or length of hospital stay (50+/
      19 versus 45+/-23 days) between patients receiving ICP or multidisciplinary care.
      Patients receiving conventional multidisciplinary care improved significantly
      faster between 4 and 12 weeks (median change in Barthel Activities of Daily
      Living Index 6 versus 2; P<0.01) and had higher Quality of Life scores at 12
      weeks (65 versus 59; P=0.07) and 6 months (72 versus 63; P<0.005). There were no
      significant differences in the mean duration of physiotherapy (42.8+/-41.2 versus
      39.4+/-36.4 hours) or occupational therapy (8.5+/-7.5 versus 8.0+/-7.5 hours)
      received between the 2 groups. CONCLUSIONS: ICP management offered no benefit
      over conventional multidisciplinary care on a stroke rehabilitation unit.
      Functional recovery was faster and Quality of Life outcomes better in patients
      receiving conventional multidisciplinary care.

PMID- 10926960
TI  - Mutations in the tropoelastin gene (ELN) were not found in patients with
      spontaneous cervical artery dissections.
AB  - BACKGROUND AND PURPOSE: The majority of patients with spontaneous cerebral artery
      dissection show ultrastructural alterations in dermal collagen and elastic
      fibers. METHODS: We studied the gene encoding tropoelastin (ELN) by reverse
      transcription-polymerase chain reaction and subsequent sequence analysis in 10
      patients with abnormalities in their elastic fibers. RESULTS: No mutations were
      found in the whole coding region of the ELN gene. The simultaneous visualization
      and quantification of ELN splice variants by gene scanning enabled the analysis
      of the regulation of alternative splicing of ELN mRNA. No differences could be
      detected between fibroblast cultures of the patients and a control subject.
      CONCLUSIONS: Neither mutations in the ELN gene nor dysregulation of its activity
      appears to be the cause of the connective tissue disorder that is found in most
      patients with spontaneous dissections.

PMID- 10926961
TI  - Cognitive deficits after focal cerebral ischemia in mice.
AB  - BACKGROUND AND PURPOSE: The interpretation of cognitive data in many experimental
      stroke studies is problematic because middle cerebral artery occlusion (MCAO) is
      associated with sensorimotor alterations that may become confounding factors in
      cognitive testing. The purpose of the current study was to determine if it is
      possible to measure MCAO-induced cognitive deficits by using short durations of
      ischemia that do not result in alterations in sensorimotor behavior in mice.
      METHODS: Male C57/Bl6 mice were subjected to 60 or 90 minutes of intraluminal
      MCAO or sham surgery. In the first cohort of animals (n=12/group), locomotor
      activity, balance, and coordination were evaluated 2 weeks after surgery. In a
      second cohort of animals (n=10/group), the effects of 60 minutes of MCAO on
      subsequent learning and memory were assessed with a step-down passive avoidance
      task beginning 1 week after surgery. In a third cohort of animals (n=8 to
      10/group), training in a passive avoidance task was completed before 60 minutes
      of MCAO, then retention of the task was assessed 1 week after surgery. In all
      animals, infarction size was determined after 14 days of reperfusion with use of
      cresyl violet staining and quantitative image analysis. RESULTS: There was no
      significant difference in infarction volume in the cerebral cortex or
      caudoputamen after 60 versus 90 minutes of MCAO. However, there was a significant
      increase in latency to move 1 body length in the 90-minute MCAO group compared
      with the 60-minute MCAO and sham groups. In 2 additional cohorts of animals, 60
      minute MCAO was associated with a deficit in the acquisition and retention of a
      passive avoidance task regardless of whether the task training occurred before or
      after MCAO. CONCLUSIONS: Long-term cognitive deficits can be induced in mice by
      using a short duration of MCAO (60 minutes) that does not result in concomitant
      sensorimotor deficits.

PMID- 10926962
TI  - White matter injury in spinal cord ischemia: protection by AMPA/kainate glutamate
      receptor antagonism.
AB  - BACKGROUND AND PURPOSE: Spinal cord ischemia is a serious complication of surgery
      of the aorta. NMDA receptor activation secondary to ischemia-induced release of
      glutamate is a major mechanism of neuronal death in gray matter. White matter
      injury after ischemia results in long-tract dysfunction and disability. The
      AMPA/kainate receptor mechanism has recently been implicated in white matter
      injury. METHODS: We studied the effects of AMPA/kainate receptor blockade on
      ischemic white matter injury in a rat model of spinal cord ischemia. RESULTS:
      Intrathecal administration of an AMPA/kainate antagonist, 6-nitro-7-sulfamoyl-(f)
      quinoxaline-2, 3-dione (NBQX), 1 hour before ischemia reduced locomotor deficit,
      based on the Basso-Beattie-Bresnahan scale (0=total paralysis; 21=normal) (sham:
      21+/-0, n=3; saline: 3.7+/-4.5, n=7; NBQX: 12. 7+/-7.0, n=7, P<0.05) 6 weeks
      after ischemia. Gray matter damage and neuronal loss in the ventral horn were
      evident after ischemia, but no difference was noted between the saline and NBQX
      groups. The extent of white matter injury was quantitatively assessed, based on
      axonal counts, and was significantly less in the NBQX as compared with the saline
      group in the ventral (sham: 1063+/-44/200x200 microm, n=3; saline: 556+/-104,
      n=7; NBQX: 883+/-103, n=7), ventrolateral (sham: 1060+/-135, n=3; saline: 411+/
      66, n=7; NBQX: 676+/-122, n=7), and corticospinal tract (sham: 3391+/-219, n=3;
      saline: 318+/-23, n=7; NBQX: 588+/-103, n=7) in the white matter on day 42.
      CONCLUSIONS: Results indicate severe white matter injury in the spinal cord after
      transient ischemia. NBQX, an AMPA/kainate receptor antagonist, reduced ischemia
      induced white matter injury and improved locomotor function.

PMID- 10926963
TI  - Dehydroepiandrosterone sulfate is neuroprotective in a reversible spinal cord
      ischemia model: possible involvement of GABA(A) receptors.
AB  - BACKGROUND AND PURPOSE: Dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS)
      may function as neurotrophic or neuroprotective factors to protect central
      nervous system (CNS) neurons against a variety of insults, including
      excitotoxicity. The present study evaluated the pharmacological effects of DHEAS
      in a reversible spinal cord ischemia model. METHODS: DHEAS was administered (50
      mg/kg IV) 5 or 30 minutes after the start of occlusion to groups of rabbits
      exposed to ischemia induced by temporary (15 to 60 minutes) occlusion of the
      infrarenal aorta. The group P(50) represents the duration of ischemia (in
      minutes) associated with 50% probability of resultant permanent paraplegia.
      RESULTS: The P(50) of the vehicle-treated control group, when behavioral analysis
      was assessed 18 hours after aortal occlusion, was 28.8+/-2.0 minutes.
      Neuroprotection was demonstrated if a drug significantly prolonged the P(50)
      compared with the vehicle-treated control group. Treatment with DHEAS at 5
      minutes significantly (P<0.05) prolonged the P(50) of the group to 36.8+/-3.9
      minutes. In addition, the DHEAS effect appeared durable, because a significant
      difference between the control and DHEAS-treated groups was still measurable at
      the 4-day time point. At 4 days, the P(50) of the control group was 26.1+/-2.2
      minutes, whereas the P(50) for the DHEAS-treated group was 38.6+/-5. 9 minutes.
      DHEAS was not neuroprotective if administered 30 minutes after occlusion. In
      addition, the GABA(A) antagonist bicuculline abolished the neuroprotective effect
      of DHEAS. CONCLUSIONS: The present study suggests that neurosteroids may have
      substantial therapeutic benefit for the treatment of ischemic stroke.

PMID- 10926964
TI  - Cerebral blood flow and blood volume measured by magnetic resonance imaging bolus
      tracking after acute stroke in pigs: comparison with [(15)O]H(2)O positron
      emission tomography.
AB  - BACKGROUND AND PURPOSE: Early and accurate assessments of cerebral ischemia allow
      therapy to be tailored to individual stroke patients. We examined the feasibility
      of using a novel method for measuring cerebral blood flow (CBF) of ischemic
      tissue based on MRI after middle cerebral artery occlusion (MCAO). Moreover, the
      regional correlations between CBF and cerebral blood volume (CBV) were
      investigated in the regions with acute ischemic stroke. METHODS: CBF and CBV were
      measured before and after MCAO or reperfusion by positron emission tomography
      (PET) in 13 pigs. Just after the PET scans, CBF and CBV were measured by MR bolus
      tracking and were compared with results obtained by PET at 6 hours after
      permanent MCAO or reperfusion. The infarction was verified histologically.
      RESULTS: The MR method yielded parametric CBF and CBV maps with tissue contrast
      in good agreement with parametric PET images, which demonstrated hypoperfused and
      hyperperfused areas after MCAO or reperfusion. Both MRI and PET technology showed
      that CBF values below 60% of the contralateral value induced a reduction of CBV,
      which committed the tissue to infarction. CONCLUSIONS: The novel MR method
      provides accurate measurement of CBF and CBV in acute stroke and hence gives
      useful information for planning the appropriate therapeutic intervention.

PMID- 10926965
TI  - Serial MRI after transient focal cerebral ischemia in rats: dynamics of tissue
      injury, blood-brain barrier damage, and edema formation.
AB  - BACKGROUND AND PURPOSE: With the advent of thrombolytic therapy for acute stroke,
      reperfusion-associated mechanisms of tissue injury have assumed greater
      importance. In this experimental study, we used several MRI techniques to monitor
      the dynamics of secondary ischemic damage, blood-brain barrier (BBB)
      disturbances, and the development of vasogenic edema during the reperfusion phase
      after focal cerebral ischemia in rats. METHODS: Nineteen Sprague-Dawley rats were
      subjected to transient middle cerebral artery occlusion of 30 minutes, 60
      minutes, or 2.5 hours with the suture occlusion model. MRI, including diffusion
      weighted imaging (DWI), T2-weighted imaging, perfusion-weighted imaging, and T1
      weighted imaging, was performed 5 to 15 minutes before reperfusion, as well as
      0.5, 1.5, and 2.5 hours and 1, 2, and 7 days after withdrawal of the suture.
      Final infarct size was determined histologically at 7 days. RESULTS: In the 30
      minute ischemia group (and partially also after 60 minutes), DWI abnormalities
      reversed transiently during the early reperfusion period but recurred after 1
      day, probably due to secondary ischemic damage. After 2.5 hours of ischemia, DWI
      abnormalities no longer reversed, and signal intensity on both DWI and T2
      weighted images increased rapidly in the previously ischemic region due to BBB
      damage (enhancement on postcontrast T1-weighted images) and edema formation.
      Early BBB damage during reperfusion was found to be predictive of relatively
      pronounced edema at subacute time points and was probably related to the
      increased mortality rates in this experimental group (3 of 7). CONCLUSIONS:
      Reperfusion after short periods of ischemia (30 to 60 minutes) appears to be
      mainly complicated by secondary ischemic damage as shown by the delayed
      recurrence of the DWI lesions, whereas BBB damage associated with vasogenic edema
      becomes a dominant factor with longer occlusion times (2.5 hours).

PMID- 10926967
TI  - Effects of delayed intraischemic and postischemic hypothermia on a focal model of
      transient cerebral ischemia in rats.
AB  - BACKGROUND AND PURPOSE: Intraischemic mild hypothermia has been shown to be
      neuroprotective in reducing cerebral infarction in transient focal ischemia. As a
      more clinical relevant issue, we investigated the effect of delayed intraischemic
      and postischemic hypothermia on cerebral infarction in a rat model of reversible
      focal ischemia. We also examined the effect of hypothermia on the inflammatory
      response after ischemia-reperfusion to assess the neuroprotective mechanism of
      brain hypothermia. METHODS: Rats were subjected to 2 hours of middle cerebral
      artery occlusion followed by 22 hours of reperfusion under the following
      protocols: (1) rats were treated with normothermia (37.0 degrees C, 4 hours) and
      then housed in room temperature (25 degrees C, 18 hours) and (2) rats were
      treated with hypothermia (33.0 degrees C, 4 hours, brain temperature modulation
      was started 30 minutes before the reperfusion) and then housed in cold
      temperature (5 degrees C, 18 hours). Animals were killed 24 hours after the onset
      of ischemia. The infarct volume was examined with 2,3,5-triphenyl-tetrazolium
      chloride staining. The accumulation of polymorphonuclear leukocytes (PMNLs) and
      the expression of intercellular adhesion molecule-1 mRNA were evaluated in both
      groups. RESULTS: A significant reduction (P<0.05) in infarct volume was found in
      the hypothermia group compared with the normothermia group. Compared with the
      normothermia group, hypothermic treatment also significantly reduced the
      accumulation of PMNLs (P<0.01) and inhibited the overexpression of intercellular
      adhesion molecule-1 mRNA at 22 hours of reperfusion after 2 hours of ischemia.
      CONCLUSIONS: Ischemic brain damage can be reduced with delayed intraischemic and
      prolonged postischemic hypothermia in a focal model of transient cerebral
      ischemia in rats. The neuroprotective mechanism of hypothermia may be mediated by
      suppression of PMNL-mediated inflammatory response after ischemia-reperfusion in
      this model.

PMID- 10926966
TI  - Role of endothelial nitric oxide generation and peroxynitrite formation in
      reperfusion injury after focal cerebral ischemia.
AB  - BACKGROUND AND PURPOSE: Reperfusion injury is one of the factors that unfavorably
      affects stroke outcome and shortens the window of opportunity for thrombolysis.
      Surges of nitric oxide (NO) and superoxide generation on reperfusion have been
      demonstrated. Concomitant generation of these radicals can lead to formation of
      the strong oxidant peroxynitrite during reperfusion. METHODS: We have examined
      the role of NO generation and peroxynitrite formation on reperfusion injury in a
      mouse model of middle cerebral artery occlusion (2 hours) and reperfusion (22
      hours). The infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride
      staining; blood-brain barrier permeability was evaluated by Evans blue
      extravasation. Nitrotyrosine formation and matrix metalloproteinase-9 expression
      were detected by immunohistochemistry. RESULTS: Infarct volume was significantly
      decreased (47%) in animals treated with the nonselective nitric oxide synthase
      (NOS) inhibitor N(omega)-nitro-L-arginine (L-NA) at reperfusion. The specific
      inhibitor of neuronal NOS, 7-nitroindazole (7-NI), given at reperfusion, showed
      no protection, although preischemic treatment with 7-NI decreased infarct volume
      by 40%. Interestingly, prereperfusion administration of both NOS inhibitors
      decreased tyrosine nitration (a marker of peroxynitrite toxicity) in the ischemic
      area. L-NA treatment also significantly reduced vascular damage, as indicated by
      decreased Evans blue extravasation and matrix metalloproteinase-9 expression.
      CONCLUSIONS: These data support the hypothesis that in addition to the
      detrimental action of NO formed by neuronal NOS during ischemia, NO generation at
      reperfusion plays a significant role in reperfusion injury, possibly through
      peroxynitrite formation. Contrary to L-NA, failure of 7-NI to protect against
      reperfusion injury suggests that the source of NO is the cerebrovascular
      compartment.

PMID- 10926968
TI  - Superoxide generation links nociceptin/orphanin FQ (NOC/oFQ) release to impaired
      N-methyl-D-aspartate cerebrovasodilation after brain injury.
AB  - BACKGROUND AND PURPOSE: Although activation of the N-methyl-D-aspartate (NMDA)
      receptor is thought to contribute to altered cerebrovascular regulation after
      traumatic brain injury, the effects of such injury on the vascular response to
      NMDA itself has been less well appreciated. The newly described opioid
      nociceptin/orphanin FQ (NOC/oFQ) elicits pial artery dilation, at least in part,
      in a prostaglandin-dependent manner and is released into cerebrospinal fluid
      after fluid percussion brain injury (FPI). Generation of superoxide anion (O(2)(
      )) occurs after FPI, and a byproduct of cyclooxygenase metabolism is the
      generation of O(2)(-). This study was designed to determine whether NOC/oFQ
      generates O(2)(-), which in turn could link NOC/oFQ release to impaired NMDA
      induced pial artery dilation after FPI. METHODS: Injury of moderate severity (1.9
      to 2.1 atm) was produced by the lateral FPI technique in anesthetized newborn
      pigs equipped with a closed cranial window. Superoxide dismutase-inhibitable
      nitroblue tetrazolium (NBT) reduction was determined as an index of O(2)(-)
      generation. RESULTS: Under non-brain injury conditions, topical NOC/oFQ (10(
      )(10) mol/L, the concentration present in cerebrospinal fluid after FPI)
      increased superoxide dismutase-inhibitable NBT reduction from 1+/-1 to 20+/-3
      pmol/mm(2) but had no effect itself on pial artery diameter. Indomethacin (5
      mg/kg IV) blunted such NBT reduction (1+/-1 to 6+/-2 pmol/mm(2)), whereas the
      NOC/oFQ receptor antagonist [F/G] NOC/oFQ (1-13) NH(2) (10(-)(6) mol/L) blocked
      NBT reduction. [F/G] NOC/oFQ (1-13) NH(2) and indomethacin also blunted the NBT
      reduction observed after FPI (1+/-1 to 15+/-1 versus 1+/-1 to 4+/-1 versus 1+/-1
      to 4+/-1 pmol/mm(2) for sham, NOC/oFQ antagonist, and indomethacin-treated
      animals, respectively). NMDA (10(-)(8) and 10(-)(6) mol/L)-induced pial artery
      dilation was reversed to vasoconstriction after FPI, and [F/G] NOC/oFQ (1-13)
      NH(2) attenuated such vasoconstriction (sham 9+/-1% and 16+/-1% versus FPI -7+/
      1% and -12+/-1% versus FPI-[F/G] NOC/oFQ (1-13) NH(2)-pretreated animals -2+/-1%
      and -3+/-1%). Indomethacin and the free radical scavengers polyethylene glycol
      superoxide dismutase and catalase also partially restored NMDA-induced
      vasodilation. CONCLUSIONS: These data show that NOC/oFQ, in concentrations
      present in cerebrospinal fluid after FPI, increased O(2)(-) production in a
      cyclooxygenase-dependent manner and contributes to such production after FPI.
      These data show that NOC/oFQ contributes to impaired NMDA-induced pial artery
      dilation after FPI. Therefore, these data suggest that cyclooxygenase-dependent
      O(2)(-) generation links NOC/oFQ release to impaired NMDA-induced
      cerebrovasodilation after brain injury.

PMID- 10926969
TI  - Brain stem stroke causing baroreflex failure and paroxysmal hypertension.
AB  - BACKGROUND: Paroxysmal neurogenic hypertension has been associated with a variety
      of diseases affecting the brain stem but has only rarely been reported after
      brain stem stroke. The mechanism is thought to involve increased sympathetic
      activity and baroreflex dysfunction. We undertook microneurographic recordings of
      muscle sympathetic nerve activity (MNSA) during beat-to-beat blood pressure (BP)
      monitoring to investigate this hypothesis. CASE DESCRIPTION: We investigated a 75
      year-old woman who developed paroxysmal hypertension (BP 220/110 mm Hg) after a
      large left-sided medullary infarct. The paroxysms were triggered by changes in
      posture and were accompanied by tachycardia, diaphoresis, and headache. Serum
      catecholamines were substantially increased (norepinephrine level, 23.9 nmol/L 9
      days after stroke; normal level, <3.8 nmol/L), and heart rate variability,
      measured by spectral analysis, was decreased in both low- and high-frequency
      domains (0.04 and 0.06 ms(2), respectively; normal level, 0.14+/-0.02 ms(2)).
      MNSA was increased in frequency (61 bursts per minute; normal level, 34+/-18
      bursts per minute), and the burst amplitude was not inversely related to
      diastolic BP. BP and MNSA responses to cold pressor and isometric handgrip
      stimuli were intact. CONCLUSIONS: Extensive unilateral infarction of the brain
      stem in the region of the nucleus tractus solitarius may result in partial
      baroreflex dysfunction, increased sympathetic activity, and neurogenic paroxysmal
      hypertension.

PMID- 10926970
TI  - An uncommon cause of recurrent strokes: Tropheryma whippelii endocarditis.
AB  - BACKGROUND: Cardiac involvement in Whipple's disease is not an uncommon
      phenomenon in autopsies, but its clinical occurrence is often overshadowed by
      gastrointestinal symptoms. We report a very atypical manifestation of this
      disorder. SUMMARY OF REPORT: An extraordinary presentation of an extremely long
      lasting, culture-negative endocarditis caused by Tropheryma whippelii is
      described, the clinical consequence of which has become apparent in recurrent
      strokes. CONCLUSIONS: Cardiac involvement of Whipple's disease should always be
      considered in culture and serologically negative endocarditis. The polymerase
      chain reaction technique may be a useful tool to confirm a presumed diagnosis of
      T whippelii endocarditis and consequently to apply an effective treatment
      regimen.

PMID- 10926971
TI  - Evaluation of measures used to assess quality of life after stroke.
AB  - BACKGROUND AND PURPOSE: Assessment of quality of life (QOL) after stroke is
      becoming common with the recognition that evaluation of treatment should include
      quality as well as quantity of survival. This article will outline the main
      conceptual and methodological issues in QOL assessment, highlight advantages and
      disadvantages of measures used in stroke QOL research, and discuss some
      unresolved issues. SUMMARY OF REVIEW: We undertook a MEDLINE search using the
      keywords "stroke" and "quality of life" and reviewed 3 key texts on QOL
      measurement in stroke. Fifteen generic and 10 condition-specific measures used to
      assess QOL in stroke were identified and evaluated with the following criteria:
      reliability, validity, responsiveness, precision, acceptability, suitability for
      proxy respondents, mode of administration, and use of patient-centered approaches
      in development. Domains covered and level of comprehensiveness varied widely
      between generic and stroke-specific measures. No stroke-specific instruments used
      patient-centered approaches in their development. Four stroke-specific measures
      (Frenchay Activities Index, Niemi QOL scale, Ferrans and Powers QOL Index-Stroke
      Version, and Stroke-Adapted Sickness Impact Profile [SA-SIP30]) provided evidence
      of reliability and validity. CONCLUSIONS: The need remains for a patient
      centered, psychometrically robust, stroke-specific QOL measure. Patients should
      be involved in each stage of instrument development. Caution is needed in the
      selection of an instrument to measure QOL after stroke. Although the Ferrans and
      Powers QOL Index-Stroke Version, Niemi QOL scale, SA-SIP30, and Sickness Impact
      Profile come closest to satisfying many of the criteria outlined in this article,
      the selection of any individual instrument depends on the specific goals and
      constraints of a particular study.

PMID- 10926972
TI  - Posterior circulation ischemia: then, now, and tomorrow. The Thomas Willis
      Lecture-2000.

PMID- 10926973
TI  - Clototripsy?

PMID- 10926974
TI  - Contrast-enhanced transcranial color-coded sonography in acute cerebral
      infarction.

PMID- 10926976
TI  - Abstracts of literature

PMID- 10926975
TI  - Measurement of cerebral blood flow volume in healthy adults using color duplex
      sonography.

PMID- 10926977
TI  - Disk hemorrhage is a significantly negative prognostic factor in normal-tension
      glaucoma.
AB  - PURPOSE: We investigated the relationship between disk hemorrhage in normal
      tension glaucoma and the progression of visual field defects and, additionally,
      whether hemorrhage plays a role in the pathogenic process of the chronic disease.
      METHODS: We retrospectively reviewed the charts of 70 patients with normal
      tension glaucoma (mean follow-up, 5.6 years) who were not medicated for glaucoma,
      and we applied a regression analysis of survival data based on the Cox
      proportional hazards model. Several clinical factors were investigated to find a
      possible association with the progression of glaucomatous visual field defined by
      two different definitions: one by mean deviation change and the other by glaucoma
      change probability analysis. RESULTS: Disk hemorrhage, corrected-pattern standard
      deviation, age, systolic blood pressure, and pulse rate had a significant
      influence on the visual field defect. The cumulative probability of progression
      of visual field loss was significantly greater for patients with disk hemorrhage
      than for patients without disk hemorrhage by either criterion for progression (P
      </=.0008, logrank test). All eyes that had at least two occurrences of disk
      hemorrhage showed progression, whereas only three of nine eyes showed progression
      in the nonrecurrent disk hemorrhage group by the glaucoma change probability
      analysis. The difference was statistically significant (P <.0001, Fisher's exact
      probability test). Furthermore, there was a significant relationship between the
      location of the disk hemorrhage and the area of the progression of visual field
      loss in 65.4% of progressive patients with disk hemorrhage. CONCLUSIONS: Several
      clinical factors other than intraocular pressure are significantly associated
      with the progression of visual field loss during the natural course of normal
      tension glaucoma. Among these, disk hemorrhage is a significantly negative
      prognostic factor in patients with normal-tension glaucoma and may be a sign of
      progressive damage of the retinal nerve fiber layer, leading to functional
      deterioration of the visual field.

PMID- 10926978
TI  - Effect of corneal polarization axis on assessment of retinal nerve fiber layer
      thickness by scanning laser polarimetry.
AB  - PURPOSE: Scanning laser polarimetry uses an anterior segment compensating device
      that assumes a fixed axis of corneal birefringence, which we call the corneal
      polarization axis. The purpose of this investigation was to establish the
      distribution of corneal polarization axes among a population of normal eyes and
      to evaluate the relationship between corneal polarization axis and posterior
      segment retardation. METHODS: We constructed a noninvasive slit lamp-mounted
      device incorporating two crossed linear polarizers and an optical retarder in
      order to measure the slow axis of corneal birefringence. Normal subjects
      underwent corneal polarization axis measurement. A subset of eyes underwent
      scanning laser polarimetry of the peripapillary retinal nerve fiber layer (n =
      32) and macula (n = 29), and retardation measurements were evaluated in each
      group. RESULTS: One hundred eighteen eyes of 63 normal subjects (35 female, 28
      male) underwent corneal polarization axis measurement (mean age, 45.5 +/- 17.1
      years). Six eyes (5.1%) demonstrated unmeasurable corneal polarization. In the
      remaining 112 eyes, the mode of the corneal polarization axis distribution was 10
      to 20 degrees nasally downward (range, 90 degrees nasally downward to 54 degrees
      nasally upward). A significant (P <.0001) correlation was observed between fellow
      eyes (R(2) =.52), with a mean difference of 11.2 +/- 10.5 degrees (range, 0-52
      degrees). Corneal polarization axis was significantly associated (R(2) =.52-.84)
      with retinal nerve fiber layer and macula summary retardation parameters (average
      thickness, ellipse average, superior and inferior average, superior and total
      integral; P <.0001 for all groups). CONCLUSIONS: The mean corneal polarization
      axis among normal corneas is nasally downward; however, considerable
      intraindividual and interindividual variability exists. The linear relationship
      between corneal polarization axis and posterior segment retardation parameters is
      responsible, in part, for the wide distribution of retinal nerve fiber layer
      thickness data generated by scanning laser polarimetry.

PMID- 10926979
TI  - Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce
      intraocular pressure.
AB  - PURPOSE: To evaluate the efficacy and safety of brimonidine compared with
      dorzolamide given three times daily as monotherapy in patients with primary open
      angle glaucoma or ocular hypertension. METHODS: In a double-masked, multicenter,
      crossover comparison in 40 patients, qualified patients were washed out from
      their previous medication and randomized to dorzolamide 2% or brimonidine 0.2%
      for the first 6-week treatment period. Patients then were washed out for 2 weeks
      and started on the opposite medication for the second 6-week period. RESULTS:
      Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 +/- 2.0 mm
      Hg. This study found that the 8:00 AM trough intraocular pressure after 6 weeks
      of therapy for dorzolamide was 20. 7 +/- 3.1 mm Hg and for brimonidine 20.8 +/-
      3.2 mm Hg (P =.99). The peak intraocular pressure (2 hours after dosing) for
      dorzolamide was 18.6 +/- 3.4 mm Hg and for brimonidine 17.8 +/- 2.7 mm Hg (P =.10
      ). Dorzolamide caused more stinging upon instillation (P <.01) and brimonidine
      more itching (P =.01). No statistical differences existed between groups for
      systemic adverse events. Six patients, all on brimonidine, were discontinued from
      a treatment period early. Of these, two were discontinued for inadequate pressure
      control, two with dizziness and fatigue, one with ocular pain, and one for
      lifestyle reasons (P =.07). CONCLUSIONS: This study found similar efficacy and
      safety between monotherapy treatment with dorzolamide or brimonidine when each
      was given three times daily to patients with ocular hypertension or primary open
      angle glaucoma.

PMID- 10926980
TI  - Interocular difference in progression of glaucoma correlates with interocular
      differences in retrobulbar circulation.
AB  - PURPOSE: To evaluate the correlation between interocular difference in
      progression of glaucomatous damage and interocular differences in retrobulbar
      blood flow. METHODS: On the basis of a retrospective analysis of visual fields,
      progressive damage was identified in 20 patients with primary open-angle
      glaucoma. As a parameter of interocular difference in progression of visual field
      damage, the angle (gamma) between the regression lines of the visual field index
      mean defect over time per eye was calculated for each subject. The relationship
      between the angle gamma and interocular differences in intraocular pressure and
      retrobulbar color Doppler imaging parameters was analyzed by a multiple linear
      regression analysis in a stepwise forward approach. RESULTS: With larger
      interocular differences in progression of glaucomatous damage, lower mean blood
      flow velocities in the ophthalmic artery (partial r = -.69; P <. 0016), higher
      resistivity indices in the central retinal artery (partial r =.48; P <.0456), and
      higher peak systolic velocities in the ophthalmic artery (partial r =.52; P
      <.0285) were noted in the eyes with more marked progression of damage (multiple r
      =.71; P <. 0099). Interocular differences in progression of visual field damage
      were not related to intraocular pressure or extent of visual field damage.
      CONCLUSION: Independent of the extent of the interocular difference in
      glaucomatous damage and intraocular pressure, interocular difference in
      progression of glaucomatous visual field damage correlates with interocular
      difference in retrobulbar hemodynamic parameters.

PMID- 10926981
TI  - Measurement of microcirculation in the optic nerve head by laser speckle
      flowgraphy and scanning laser Doppler flowmetry.
AB  - PURPOSE: To evaluate and compare blood flow measurements by laser speckle
      flowgraphy and scanning laser Doppler flowmetry in the optic nerve head of normal
      volunteers. METHODS: This prospective study included 60 eyes of 60 normal
      volunteers (50.0 years; range, 21 to 77 years). Measurements were taken at the
      temporal neuroretinal rim away from visible vessels. The square blur rate, a
      quantitative index of relative blood velocity, was measured by laser speckle
      flowgraphy. Using scanning laser Doppler flowmetry, volume, flow, and velocity
      were measured at the same neuroretinal rim locations. RESULTS: The average square
      blur rate, volume, flow, and velocity were 7.11 +/- 1.65, 7.74 +/- 3.19, 151.85
      +/- 70.63, and 0.53 +/- 0. 23 arbitrary units, respectively (n = 60). Square blur
      rate correlated significantly with flow and velocity (r =.361, P =.005; r =.359,
      P =.005, respectively). However, there was no significant correlation between
      square blur rate and volume (r =.101, P =.441). Although square blur rate
      decreased significantly with increasing age (r = -.375, P =.003), volume, flow,
      or velocity showed no significant correlation with age (r = -.249, P =.054; r = 
      .166, P =. 205; r = -.143, P =.275, respectively). Square blur rate also
      decreased significantly with mean blood pressure (r = -.315, P =. 014), but
      volume, flow, or velocity showed no significant correlation with mean blood
      pressure (r = -.159, P =.225; r = -.059, P =.654; r = -.043, P =.742,
      respectively). CONCLUSION: We found only a weak correlation between the blood
      flow indexes, as measured by laser speckle flowgraphy and scanning laser Doppler
      flowmetry because of basic differences in the principles of measurement.

PMID- 10926982
TI  - Accuracy of glaucoma detection with frequency-doubling perimetry.
AB  - PURPOSE: To determine the accuracy of glaucoma detection by frequency-doubling
      perimetry. METHODS: Stereoview optic nerve photographs, visual field examination,
      intraocular pressure measurements, medical and ocular history, and a screening
      and full threshold frequency-doubling perimetry examination were performed in a
      prospective study of consecutive subjects. Inclusion criteria included age of 45
      years or older, absence of ocular disease other than glaucoma, cataract, or mild
      drusen, and Snellen visual acuity of 20/60 or better. A total of 125 eyes in 102
      glaucoma subjects and 95 eyes of 95 normal subjects were included. Each eye was
      classified as "normal," "glaucoma," or "uncertain" by each of three
      ophthalmologists on the basis of all available clinical information with the
      exception of frequency-doubling perimetry results. Those in the glaucoma group
      were subclassified as having early (n = 51), moderate (n = 42), or severe (n =
      32) glaucoma on the basis of automated Humphrey visual field criteria. In the
      glaucoma group, two eyes from a subject were allowed to be included (23 of 102
      subjects) if they differed in level of damage because they were never analyzed
      within the same statistical analysis. RESULTS: Several diagnostic algorithms were
      evaluated. Algorithms based on the most depressed single point, pair of adjacent
      points, and cluster of three points performed nearly identically. For the
      screening test, if any abnormality was identified, specificity was 95%, whereas
      sensitivity was 39%, 86%, and 100% for early, moderate, and severe glaucoma,
      respectively. For the full threshold test, with at least one point depressed to
      the P < 0.5% level, specificity measured 91%, whereas sensitivity was 35%, 88%,
      and 100% for early, moderate, and severe glaucoma, respectively. The two global
      indices, mean deviation and pattern standard deviation, were also evaluated and
      were generally less accurate. CONCLUSION: Frequency-doubling perimetry, which is
      rapid and easily administered, is effective at detecting moderate and severe
      disease and appears well suited for glaucoma screening.

PMID- 10926983
TI  - Epithelial ingrowth after laser in situ keratomileusis.
AB  - PURPOSE: To report the incidence and risk factors for clinically significant
      epithelial ingrowth after laser in situ keratomileusis as well as the recurrence
      rate and visual outcomes after its treatment. METHODS: We defined clinically
      significant epithelial ingrowth as that which required surgical removal. From a
      cohort of 3, 786 eyes that underwent primary laser in situ keratomileusis from
      February 1996 to August 1998 and its derivative of 480 eyes that later underwent
      enhancement laser in situ keratomileusis by one surgeon (R.K.M.), we identified
      all eyes with clinically significant epithelial ingrowth. RESULTS: The incidence
      of significant epithelial ingrowth after primary treatment was 35 (0.92%) of
      3,786 eyes. The incidence after enhancement treatment was eight (1.7%) of 480
      eyes (p = NS). Fourteen of 43 eyes had a postoperative epithelial defect
      associated with subsequent development of epithelial ingrowth. Six of 43 eyes had
      loose epithelium intraoperatively, suggesting epithelial basement membrane
      dystrophy. Epithelial ingrowth was treated by lifting the flap, scraping the bed
      and the posterior surface of the flap, and replacing the flap without the use of
      caustic agents. In 42 of 43 eyes, the epithelial ingrowth under the flap was
      continuous with the surface epithelium. Clinically significant ingrowth recurred
      in 10 of 43 eyes after the initial surgical removal. CONCLUSIONS: Clinically
      significant epithelial ingrowth is an infrequent complication of laser in situ
      keratomileusis. We hypothesize that epithelial ingrowth is secondary to
      postoperative invasion under the flap by surface epithelial cells rather than
      intraoperative implantation of epithelial cells. Treatment should consist of
      complete mechanical removal of epithelium from the posterior surface of the
      corneal flap and keratectomy bed and ensuring tight apposition of the flap with
      the bed.

PMID- 10926984
TI  - Quantitative topographic irregularity as a predictor of spectacle-corrected
      visual acuity after refractive surgery.
AB  - PURPOSE: To evaluate a new topographic index called topographic irregularity as a
      quantitative predictor of corrected vision after refractive surgery. METHODS: We
      defined topographic irregularity as the summed difference at all points between a
      topographic refractive corneal power map and its best-fit spherocylinder. We
      prospectively studied 107 eyes of 107 patients 3 months after a variety of
      refractive procedures. Topographic irregularity was calculated from topographic
      maps, and the correlation between topographic irregularity and spectacle
      corrected visual acuity was determined using both high-contrast and low-contrast
      acuity charts. This correlation was compared with correlations for the surface
      regularity index and the surface asymmetry index. Next, we analyzed 54 of these
      topographic maps to create a regression scale relating surface regularity index,
      surface asymmetry index, and topographic irregularity to predict spectacle
      corrected visual acuity. This scale was then used to predict spectacle-corrected
      visual acuity on the remaining 53 postoperative patients. RESULTS: The
      correlation of topographic irregularity with spectacle-corrected visual acuity
      (R(2) =.36) was comparable to the correlation for the surface regularity index
      (R(2) =.36) and stronger than for the surface asymmetry index (R(2) =.11) when
      spectacle-corrected visual acuity was measured with high-contrast eye charts.
      Topographic irregularity correlated more strongly with spectacle-corrected visual
      acuity (R(2) =.42) than either the surface regularity index (R(2) =.28) or the
      surface asymmetry index (R(2) =.14) when spectacle-corrected visual acuity was
      measured with low-contrast eye charts. Using the regression scale, prediction of
      high-contrast and low-contrast spectacle-corrected visual acuity from topographic
      irregularity was superior to or comparable to predictions using the surface
      regularity index and the surface asymmetry index. CONCLUSIONS: Topographic
      irregularity has a closer correlation with spectacle-corrected visual acuity than
      existing topographic indexes. Topographic irregularity is also an accurate
      predictor of spectacle-corrected visual acuity and may be a more sensitive tool
      for evaluating postoperative visual performance than current topographic
      measures.

PMID- 10926985
TI  - Prediction of letter contrast sensitivity using videokeratographic indices.
AB  - PURPOSE: To analyze the relationship between corneal topography and letter
      contrast sensitivity. METHOD: Experiments were conducted on 59 eyes of 51
      patients who had best spectacle-corrected visual acuity of 20/20 or better and no
      ocular pathology except for the corneal shape. Thirty-nine eyes had an abnormal
      topographic pattern resulting from keratoconus, and the other 20 eyes showed a
      normal topographic pattern. Videokeratography was performed with the TMS-2
      videokeratoscope, and the surface regularity index, surface asymmetry index, and
      coefficient of variation of power were obtained for each subject. Letter contrast
      sensitivity was measured with the CSV-1000LV with spectacle correction. The
      correlation between the number of correct letters and topographic indices was
      calculated. RESULTS: The abnormal topography group had a significantly greater
      loss of letter contrast sensitivity (median = 20 letters) than the normal control
      (median = 23 letters; P =.0001). There were statistically significant
      correlations between number of correct letters and the coefficient of variation
      of power (r = -.77; P =. 001), number of correct letters and surface regularity
      index (r = -. 76, P =.001), and the number of correct letters and surface
      asymmetry index (r = -.64; P =.001). The linear regression equation between
      number of correct letters and the coefficient of variation of power was the
      number of correct letters = -0.05 x the coefficient of variation of power + 23.2.
      CONCLUSIONS: Our results suggest that subtle visual deteriorations, which are
      barely detected by contrast sensitivity testing, can be predicted objectively by
      the corneal topographic indices.

PMID- 10926986
TI  - Immunomodulatory therapy for chronic tubulointerstitial nephritis-associated
      uveitis.
AB  - PURPOSE: To describe the clinical course and treatment with immunomodulatory
      agents in patients with tubulointerstitial nephritis and uveitis syndrome.
      METHODS: Retrospective analysis of the charts of six patients with
      tubulointerstitial nephritis and uveitis syndrome. RESULTS: The mean (+/-SD) age
      was 24.3 (+/-16.5) years, range 13 to 49 years. Four patients were children, and
      two were adults. Three were men, and three were women. Five of the six patients
      had anterior uveitis, and one had panuveitis. All patients had several relapses
      despite treatment with topical, regional, and oral steroids and methotrexate in
      one case. The introduction or modification of immunosuppressants (methotrexate,
      azathioprine, or cyclosporin A) achieved control of the uveitis and prevented
      relapses over a mean (+/-SD) follow-up period of 19.66 (+/-10.01) months, range 6
      to 34 months. No treatment-related side effects were observed. CONCLUSIONS:
      Tubulointerstitial nephritis and uveitis syndrome is a distinct disease entity in
      which the nephritis typically resolves, but the uveitis often becomes chronic and
      is treatment resistant. Immunomodulatory agents can achieve control of the
      inflammation and prevent relapses.

PMID- 10926987
TI  - Internal limiting membrane removal in the management of full-thickness macular
      holes.
AB  - PURPOSE: To determine the effectiveness of removal of the internal limiting
      membrane in the treatment of full-thickness macular holes. METHODS: Data were
      reviewed from a prospective study on 47 consecutive eyes with full-thickness
      macular holes undergoing vitrectomy, internal limiting membrane maculorhexis, and
      fluid-gas exchange. No eye underwent repeat macular hole surgery. A meta-analysis
      was performed to compare the outcomes of different surgical techniques in the
      treatment of full-thickness macular holes. RESULTS: The outcome measures were
      disappearance of the submacular fluid and the change in best-corrected visual
      acuity. The surgery was anatomically successful in 44 of the 46 eyes (96%) and 39
      of the eyes (85%) showed an improvement of at least two Snellen lines. Best
      corrected final vision was 20/40 in 18 (39%) eyes. No permanent complications
      specifically caused by the removal of the macular internal limiting membrane were
      detected; the minor hemorrhages and retinal edema seen in most eyes resolved
      spontaneously. Retinal detachment developed and was successfully treated in three
      eyes (7%). A meta-analysis on 1,654 eyes from published reports showed that
      internal limiting membrane maculorhexis appears to significantly (P <.0001)
      increase the anatomical and functional success rates in macular hole surgery.
      CONCLUSIONS: Internal limiting membrane removal is an important development in
      the evolving field of macular hole surgery. A randomized, prospective,
      multicenter clinical trial should be performed to determine which surgical
      technique is the most beneficial in patients with full-thickness macular holes.

PMID- 10926988
TI  - Bacterial subretinal abscess: a case report and review of the literature.
AB  - PURPOSE: To report a case of Klebsiella subretinal abscess with a successful
      visual outcome with treatment and to review the literature pertaining to focal
      intraocular infection in bacterial endophthalmitis. METHODS: Clinical data
      including medical history, findings on physical examination, blood cultures, and
      an abdominal computed tomographic scan were collected in a 32-year-old man with
      Klebsiella sepsis, liver abscesses, and a focal subretinal abscess. Ocular data
      including visual acuity, fundus photographs, fluorescein angiography, and
      ultrasound were evaluated, as were results of culture and histopathologic
      studies. RESULTS: Despite immediate intervention, including vitreous tap and
      intravitreal antibiotics, the eye deteriorated, with enlargement of the abscess.
      A pars plana vitrectomy was performed in which the subretinal abscess material
      was removed after an extensive retinectomy of the involved area in association
      with an endophotocoagulative barrier and intravitreal amikacin without gas or oil
      tamponade. Culture confirmed Klebsiella subretinal infection. A retinal
      detachment occurred 1 month postoperatively and was successfully repaired. Visual
      acuity was 20/30 and has remained stable for 14 months. CONCLUSION: Klebsiella
      endophthalmitis with subretinal abscess formation is a rare but devastating
      ocular condition. In the present case, prompt intervention with extensive
      retinectomy, complete abscess excision, and intravitreal antibiotic therapy
      resulted in unprecedented visual recovery.

PMID- 10926989
TI  - Optic disk and retinal nerve fiber layer damage after transient central retinal
      artery occlusion: an experimental study in rhesus monkeys.
AB  - PURPOSE: To evaluate the retinal tolerance time to acute ischemic insult in
      middle-aged or elderly rhesus monkeys with pre-existing atherosclerosis and
      arterial hypertension. METHODS: In 39 eyes of 39 middle-aged and elderly rhesus
      monkeys with a mean age of 19.5 +/- 2. 8 years, occlusion of the central retinal
      artery was produced by temporary clamping of the central retinal artery at its
      site of entry into the dural sheath of the optic nerve for 97 to 300 minutes.
      Stereoscopic color fundus photography and fluorescein fundus angiography were
      performed before central retinal artery occlusion and serially thereafter.
      Retinal nerve fiber layer damage and optic disk changes were assessed by
      comparing morphometric evaluation of the color fundus photographs taken before
      central retinal artery occlusion and color fundus photographs taken at the end of
      the study. RESULTS: There was a significant correlation between duration of
      central retinal artery occlusion and decreased visibility of retinal nerve fiber
      layer (P =.018) and increasing optic disk pallor (P =. 014), and a trend between
      residual retinal circulation and decreased visibility of retinal nerve fiber
      layer (P =.085) and optic disk pallor (P =.162). However, there was a marked
      interindividual variation between the length of central retinal artery occlusion
      and degree of increased optic disk pallor and decreased visibility of the retinal
      nerve fiber layer, even among eyes with similar duration of central retinal
      artery occlusion. Complete or almost total optic nerve atrophy and nerve fiber
      damage were present in all eyes in which the duration of central retinal artery
      occlusion was 240 minutes or more. CONCLUSIONS: The findings of this study,
      compared with our previous study in young healthy rhesus monkeys, indicate that
      in middle-aged or elderly atherosclerotic and arterial hypertensive rhesus
      monkeys, central retinal artery occlusion for less than 100 minutes produced no
      apparent morphometric evidence of optic nerve damage; however, central retinal
      artery occlusion of 105 minutes but less than 240 minutes produced a variable
      degree of damage; central retinal artery occlusion for 240 minutes or more
      produced total or almost total optic nerve atrophy and nerve fiber damage.

PMID- 10926990
TI  - Hemorrhage of the optic disk in normal-tension glaucoma.

PMID- 10926991
TI  - Tubulointerstitial nephritis and uveitis syndrome: recognizing the importance of
      an uncommon disease.

PMID- 10926992
TI  - Nd:YAG laser corneal disruption as adjuvant treatment for infectious crystalline
      keratopathy.
AB  - PURPOSE: To report on the use of the Nd:YAG laser corneal disruption in the
      treatment of infectious crystalline keratopathy. METHOD: Case report. A 52-year
      old woman with infectious crystalline keratopathy unresponsive to topical
      antibiotics was treated with an Nd:YAG laser to the intrastromal crystals.
      RESULTS: After Nd:YAG laser treatment, the infiltrate completely cleared within 4
      weeks. CONCLUSIONS: Nd:YAG laser treatment may be effective in disrupting the
      protective glycocalyx matrix within the intrastromal crystals, rendering the
      bacteria susceptible to topical antibiotics. This treatment should be considered
      for patients with infectious crystalline keratopathy clinically resistant to
      topical antibiotics.

PMID- 10926993
TI  - Removal of corneal foreign bodies that project into the anterior chamber: use of
      a suture needle.
AB  - PURPOSE: To describe and illustrate a simple and reliable technique for removing
      penetrating corneal foreign bodies. METHODS: A 6-mm needle was placed through the
      cornea beneath the corneal foreign body to provide support and illumination
      posteriorly. RESULTS: In eight eyes of eight patients all penetrating corneal
      foreign bodies were removed completely without severe complications. CONCLUSIONS:
      The use of a suture needle during removal of penetrating corneal foreign bodies
      is simple, effective, reliable, and inexpensive.

PMID- 10926995
TI  - Increased eyelid pigmentation associated with use of latanoprost.
AB  - PURPOSE: To report increased eyelid pigmentation as an adverse side effect
      associated with topical latanoprost. METHOD: Case report. A 62-year-old Korean
      woman with normal-tension glaucoma developed bilateral increased eyelid skin
      pigmentation 4 months after beginning treatment with latanoprost in both eyes.
      Clinical examinations were performed, and external photographs were taken.
      RESULT: Latanoprost was discontinued. Periodic examinations revealed that the
      eyelid skin pigmentation gradually diminished 1 month after the cessation of the
      drug, and decrease in pigmentation continued over 4 months of follow-up.
      CONCLUSION: An increase in eyelid skin pigmentation is a possible complication of
      topical latanoprost therapy, and the cessation of the drug can result in loss of
      induced pigmentation in humans.

PMID- 10926994
TI  - Aspergillus flavus keratitis after laser in situ keratomileusis.
AB  - PURPOSE: To report a case of fungal keratitis caused by Aspergillus flavus after
      laser in situ keratomileusis surgery. METHODS: Case report. A 24-year-old woman
      developed pain, redness, decreased vision, and an infiltrate posterior to the
      corneal flap in her right eye 3 days after laser in situ keratomileusis. On
      referral, approximately 3 weeks after laser in situ keratomileusis, examination
      of the right eye revealed light perception vision, a large full-thickness corneal
      infiltrate, and hypopyon. Corneal scrapings were taken for direct microscopic
      examination and culture. RESULTS: Corneal scraping revealed the presence of
      fungal filaments in smears and in culture. The fungus was identified as A.
      flavus. Intensive topical natamycin and systemic ketoconazole therapy was
      initiated. Despite intensive medical treatment, the infiltrate progressed and the
      patient was subjected to a therapeutic penetrating keratoplasty. There was no
      recurrence of infection after surgery. At last follow-up 4 months after surgery,
      the eye was quiet with graft edema. CONCLUSION: Fungal keratitis is a rare
      complication of laser in situ keratomileusis surgery. In a case that does not
      respond to medical treatment, early surgical intervention must be considered.

PMID- 10926996
TI  - Posterior subcapsular cataract in Degos disease.
AB  - PURPOSE: To report an association of posterior subcapsular cataract with Degos
      disease. METHOD: Case report of a 42-year-old man. RESULTS: A posterior
      subcapsular cataract developed in the patient's left eye at age 43 years, 1 year
      before his death. The diagnosis of Degos disease was confirmed pathologically by
      skin biopsy and at necropsy. CONCLUSION: Posterior subcapsular cataract may be
      associated with Degos disease in addition to previously reported findings,
      including visual field defects, third cranial nerve palsies, blepharoptosis, and
      optic atrophy.

PMID- 10926997
TI  - Tubulointerstitial nephritis and uveitis with bilateral multifocal choroiditis.
AB  - PURPOSE: To report a case of bilateral multifocal choroiditis secondary to
      tubulointerstitial nephritis and uveitis. METHODS: Case report. A 16-year-old
      women with an 11-month history of tubulointerstitial nephritis and uveitis and
      bilateral anterior uveitis developed bilateral multifocal choroiditis. After
      initial unsuccessful treatment with topical steroids, treatment was augmented by
      a 2-week course of systemic prednisone. RESULTS: Intensive steroid treatment
      resulted in steroid-induced glaucoma, which required bilateral trabeculectomies,
      but the uveitis became inactive. Two years after uveitis onset, bilateral
      intraocular pressure was normal, there were occasional (12+) anterior chamber
      cells, and inactive depigmented chorioretinal lesions on topical steroid drops.
      See also pp. 764-768, 798-799. CONCLUSIONS: Tubulointerstitial nephritis and
      uveitis usually involves only the anterior uvea, although a few cases of
      posterior uveitis have been described. This article reports a case of multifocal
      choroiditis associated with tubulointerstitial nephritis and uveitis. It is
      important for ophthalmologists to be aware of possible posterior uveal
      involvement in tubulointerstitial nephritis and uveitis so they can choose the
      most appropriate immunosuppressive therapy for the uveitis.

PMID- 10926998
TI  - Zoster sine herpete with bilateral ocular involvement.
AB  - PURPOSE: To report a case of zoster sine herpete with bilateral ocular
      involvement. METHOD: Case report. RESULTS: A 65-year-old man showed bilateral
      iridocyclitis with sectoral iris atrophy and elevated intraocular pressure
      unresponsive to steroid treatment. No cutaneous eruption was manifest on the
      forehead. A target region of varicella-zoster virus DNA sequence was amplified
      from the aqueous sample from the left eye by polymerase chain reaction. Bilateral
      iridocyclitis resolved promptly after initiation of systemic and topical
      acyclovir treatment. Secondary glaucoma was well controlled by bilateral
      trabeculectomy. CONCLUSIONS: Zoster sine herpete should be considered and
      polymerase chain reaction performed on an aqueous sample to detect varicella
      zoster virus DNA for rapid diagnosis whenever anterior uveitis accompanies the
      characteristic iris atrophy, even in the case of bilateral involvement.

PMID- 10926999
TI  - Intravitreal antiviral injections as adjunctive therapy in the management of
      immunocompetent patients with necrotizing herpetic retinopathy.
AB  - PURPOSE: To report the use of intravitreal antiviral injections as adjunctive
      therapy in the management of three immunocompetent patients with necrotizing
      herpetic retinopathy. METHOD: Case series. RESULTS: Three patients with
      necrotizing herpetic retinopathy received intravitreal antiviral injections for
      treatment of progressive retinitis, despite standard intravenous acyclovir
      therapy. The retinitis resolved and visual acuity improved after a minimum of 6
      months of follow-up in each case. CONCLUSION: Intravitreal antiviral injections
      may be a safe and efficacious adjunctive therapy in the management of patients
      with necrotizing herpetic retinopathy.

PMID- 10927000
TI  - Alcaligenes xylosoxidans and Propionibacterium acnes postoperative
      endophthalmitis in a pseudophakic eye.
AB  - PURPOSE: To report a case of persistent polymicrobial postoperative
      endophthalmitis caused by Alcaligenes xylosoxidans and Propionibacterium acnes in
      a pseudophakic eye. A. xylosoxidans is a gram-negative bacteria resistant to most
      antibiotics. METHODS: Case report. RESULTS: A 72-year-old man presented with
      clinical signs of endophthalmitis on the first postoperative day after a
      phacoemulsification procedure with posterior chamber intraocular lens, left eye.
      Initial treatment included topical, subconjunctival, and oral antibiotics. After
      initial clearing, there was recrudescence of infection on postoperative day 37
      that prompted referral of the patient to the Cullen Eye Institute. Treatment at
      that time included anterior chamber and vitreous taps with intravitreal
      antibiotic injections. Complete pars plana vitrectomy and intraocular lens
      explantation were eventually required because of persistent infection with a
      resistant organism. Cultures from the first procedure grew A. xylosoxidans and P.
      acnes. Cultures from the vitrectomy grew only A. xylosoxidans. At the final
      follow-up visit 6 months after the initial procedure. The eye was without
      inflammation with best-corrected visual acuity of 20/40. CONCLUSION: Both A.
      xylosoxidans and P. acnes can cause chronic progressive endophthalmitis after
      cataract extraction often resistant to corrective antibiotic therapy. Successful
      intervention may require complete vitrectomy with intraocular lens and capsule
      removal.

PMID- 10927002
TI  - Central retinal artery occlusion in a patient homozygous for factor V Leiden.
AB  - PURPOSE: To report an association between central retinal artery occlusion and
      homozygosity for factor V Leiden. METHOD: Case report. RESULTS: A 48-year-old
      woman with sudden loss of visual acuity in her right eye caused by a central
      retinal artery occlusion showed abnormal resistance to activated protein C and
      was homozygous for the factor V Leiden gene. CONCLUSION: Activated protein C
      resistance may be a risk factor for central retinal artery occlusion in young
      adults.

PMID- 10927001
TI  - Visual hallucinations immediately after macular photocoagulation.
AB  - PURPOSE: To evaluate the incidence of visual hallucinations after macular
      photocoagulation for choroidal neovascularization. METHODS: After macular
      photocoagulation for choroidal neovascularization, 60 consecutive patients were
      asked to respond to an orally administered questionnaire. RESULTS: Twenty-seven
      patients (45%) described photopsias, flashing lights of various colors. Ten
      additional patients (16.6%) also described structured hallucinations, including
      known or unknown faces, flowers, and geometric patterns, which occurred hours or
      a few days after photocoagulation. Patients with structured hallucinations were
      older (P =.04) and more often had subfoveal choroidal neovascularization (P
      =.005) and severe macular disease in both eyes or at least in the treated eye (P
      =.01). CONCLUSIONS: Visual hallucinations appear to be a frequent, albeit
      unrecognized, side effect of macular photocoagulation of choroidal
      neovascularization. The provision of proper information to patients may avoid
      concern about a psychiatric origin of their hallucinations.

PMID- 10927003
TI  - Rhegmatogenous retinal detachment in retinoblastoma patients undergoing
      chemoreduction and cryotherapy.
AB  - PURPOSE: To report the development of rhegmatogenous retinal detachment, with the
      retinal break adjacent to a cryotherapy scar, in three patients undergoing
      systemic chemotherapy for intraocular retinoblastoma. METHOD: Case series.
      RESULTS: Three patients with intraocular retinoblastoma were referred after poor
      response to systemic chemotherapy and local cryotherapy; three eyes of these
      three patients were noted to have rhegmatogenous retinal detachment and active
      retinoblastoma, with retinal breaks adjacent to cryotherapy scars. CONCLUSION:
      Rhegmatogenous retinal detachment may result from retinal necrosis associated
      with cryotherapy in the setting of intraocular retinoblastoma treated with
      systemic chemotherapy and local cryotherapy.

PMID- 10927004
TI  - Choroidal rupture associated with forceps delivery.
AB  - PURPOSE: To report a case of choroidal rupture associated with forceps delivery.
      METHOD: Case report. RESULTS: We examined a 4-year-old boy with a history of a
      retinal scar in the right eye. The child was delivered with forceps and had
      bitemporal ecchymoses at birth. There was no other history of trauma.
      Ophthalmoscopic examination of the right eye with a vision of counting fingers
      revealed linear scars from choroidal rupture in the posterior pole, including one
      through the macula. Anterior segment examination was normal. Examination of the
      left eye was completely normal. CONCLUSION: Ocular trauma associated with forceps
      delivery may rarely result in choroidal ruptures, even in the absence of external
      signs of injury, such as breaks in Descemet membrane.

PMID- 10927006
TI  - Idiopathic intracranial hypertension. Relationship To depression, anxiety, and
      quality of life. Neurology 2000;54:319-324

PMID- 10927005
TI  - Congenital ocular motor apraxia with autosomal dominant inheritance.
AB  - PURPOSE: To document congenital ocular motor apraxia in five first-degree
      relatives. METHODS: Case series. Five family members with a history of horizontal
      head thrusting had neuro-ophthalmologic evaluation. Magnetic resonance imaging of
      the brain was obtained in the proband. RESULTS: Four siblings (one boy and three
      girls) had congenital ocular motor apraxia. The father had head thrusting as a
      child and displayed residual signs of the disorder. Magnetic resonance imaging
      disclosed no central nervous system abnormalities in the father. CONCLUSION:
      Congenital ocular motor apraxia can be inherited as an autosomal dominant trait.

PMID- 10927008
TI  - Optic nerve damage in shaken baby syndrome. Detection By beta-amyloid precursor
      protein immunohistochemistry. Arch pathol lab med 2000;124:251-256

PMID- 10927007
TI  - The therapy of amblyopia: an analysis comparing the results of amblyopia therapy
      utilizing two pooled data sets. Trans Am ophthalmol soc 1999;97:373-390

PMID- 10927009
TI  - Retinopathy progression and visual outcomes after phacoemulsification in patients
      with diabetes mellitus. Trans Am ophthalmol soc 1999;97:435-445

PMID- 10927011
TI  - Vision and quality-of-life. Trans Am ophthalmol soc 1999;97:473-511

PMID- 10927010
TI  - Transpupillary thermotherapy as primary treatment for small choroidal melanomas.
      Trans Am ophthalmol soc 1999;97: 407-427

PMID- 10927012
TI  - Collagen type I and III synthesis by Tenon's capsule fibroblasts in culture:
      individual patient characteristics and response to mitomycin C, 5-fluorouracil,
      and ascorbic acid. Trans Am ophthalmol soc 1999;97: 513-543

PMID- 10927014
TI  - Combined exfoliation and pigment dispersion: an overlap syndrome. Trans Am
      ophthalmol soc 1999;99:297-314

PMID- 10927013
TI  - Juvenile retinoschisis: a model for diagnostic testing of x-linked ophthalmic
      disease. Trans Am ophthalmol soc 1999;97:451-464

PMID- 10927015
TI  - Achieving success with the silicone expander for overacting superior obliques.
      Trans Am ophthalmol soc 1999;97:333-342

PMID- 10927016
TI  - Mutations in a new photoreceptor-pineal gene on 17p cause leber congenital
      amaurosis. Nat gen 2000;24:79-83

PMID- 10927017
TI  - Large eyeballs in diving ichthyosaurs. Nature 1999;402:747

PMID- 10927018
TI  - Lipid metabolism as a target for potassium channel effectors.
AB  - K(+) channel effectors are widely used in the treatment of various diseases,
      including diabetes mellitus type II, hypertension, and cardiac arrhythmia. In
      addition, a constantly growing body of literature reveals that some of these
      substances, despite their direct effect on K(+) channels, may influence cellular
      lipid metabolism. As a result, membrane lipid content and cellular concentrations
      of lipid messengers are changed. Due to the dependence of K(+) channel activity
      on membrane lipids, these observations seem to be of particular importance not
      only to characterize secondary effects of K(+) channel effectors but also to
      understand the long-term effects of these agents on K(+) channel activity.

PMID- 10927019
TI  - Effects of cocaine and its oxidative metabolites on mitochondrial respiration and
      generation of reactive oxygen species.
AB  - Cocaine is capable of producing severe hepatocellular necrosis in laboratory
      animals and humans. The mechanism of cocaine hepatotoxicity is not well
      understood, but appears to result from the actions of one or more N-oxidative
      metabolites of cocaine. Mitochondria have been proposed as critical cellular
      targets for cocaine toxicity, and previous studies have found depressed
      mitochondrial respiration and increased mitochondrial generation of reactive
      oxygen species (ROS) in animals treated with cocaine. To examine the potential
      role of cocaine N-oxidative metabolites in these effects, mitochondrial
      respiration and ROS generation were examined in isolated mouse mitochondria
      treated with cocaine and its N-oxidative metabolites-norcocaine, N
      hydroxynorcocaine, and norcocaine nitroxide. Cocaine, in concentrations of 0.25
      or 0.5 mM, had no effect on state 3 respiration, state 4 respiration, respiratory
      control ratio (RCR), or ADP/O ratio. Norcocaine (0.5 mM) inhibited state 3
      respiration, and N-hydroxynorcocaine (0.5 mM) inhibited both state 3 and state 4
      respiration. Norcocaine nitroxide had the greatest effect on mitochondrial
      respiration; the lower concentration (0.25 mM) completely inhibited both state 3
      and state 4 respiration. Preincubation of mitochondria with cocaine or
      metabolites increased the inhibitory effect of norcocaine and N
      hydroxynorcocaine, but not cocaine. Cocaine, norcocaine, and N-hydroxynorcocaine
      (0.1 mM) had no effect on ROS generation during state 3 respiration, and cocaine
      and norcocaine decreased ROS generation under state 4 conditions. Norcocaine
      nitroxide interfered with the fluorescence ROS assay and could not be assessed.
      The results suggest that the effects of cocaine on mitochondrial respiration are
      due to its N-oxidative metabolites. Inhibition of mitochondrial respiration by
      the N-oxidative metabolites of cocaine may be the underlying cause for observed
      ATP depletion and subsequent cell death.

PMID- 10927020
TI  - Role of NADPH:cytochrome P450 reductase in the hypoxic accumulation and
      metabolism of BRU59-21, a technetium-99m-nitroimidazole for imaging tumor
      hypoxia.
AB  - Nitroimidazoles labeled with technetium-99m are being investigated as non
      invasive markers of tumor hypoxia. They are bioreductive compounds that require
      enzymatic reduction for retention in hypoxic cells, but little is known about the
      cellular factors affecting their accumulation in hypoxic cells. If the absolute
      accumulation of hypoxia markers is affected by enzyme levels, an inaccurate
      assessment of the hypoxic cell fraction in tumors may occur. BRU59-21, (99m)Tc
      oxo[[3,3,9, 9-tetramethyl-6-[(2-nitro-1H-imidazol-1-yl)methyl]5-oxa-4, 8
      diazadioximato]-(3-)-N,N',N",N"'] technetium (V), a technetium-99m-nitroimidazole
      that is being studied as a potential marker of tumor hypoxia, was used in the
      present study to evaluate the effect of NADPH:cytochrome P450 reductase (EC
      1.6.2.4) levels on BRU59-21 accumulation and metabolism. Metabolism of BRU59-21
      in hypoxic cellular lysates derived from Chinese hamster ovary cells
      overexpressing NADPH:cytochrome P450 reductase was 8-fold greater than in control
      cells. This effect required the presence of exogenous NADPH. The increased
      metabolism of BRU59-21 in lysates overexpressing NADPH:cytochrome P450 reductase
      was inhibited at 4 degrees and by the addition of NADPH:cytochrome P450 reductase
      inhibitors. The addition of inhibitors of other nitroreductase enzymes had no
      effect on BRU59-21 metabolism in these lysates. When the accumulation and
      metabolism of BRU59-21 were studied in stirred suspension cultures, it was found
      that cells overexpressing NADPH:cytochrome P450 reductase exhibited about a 3
      fold increase in both the hypoxic metabolism and the accumulation of BRU59-21.
      These findings suggest that NADPH:cytochrome P450 reductase is an important
      enzyme in BRU59-21 metabolism in model systems of tumor hypoxia.

PMID- 10927021
TI  - Suppression of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated aryl
      hydrocarbon receptor transformation and CYP1A1 induction by the
      phosphatidylinositol 3-kinase inhibitor 2-(4-morpholinyl)-8-phenyl-4H-1-
      benzopyran-4-one (LY294002).
AB  - Numerous flavonoids are ligands of the aryl hydrocarbon receptor (AHR) and
      function as AHR antagonists and/or agonists. LY294002 [2-(4-morpholinyl)-8-phenyl
      4H-1-benzopyran-4-one] is a widely used inhibitor of phosphatidylinositol 3
      kinase (PI 3-kinase), and is structurally related to members of the flavonoid
      family. Concentrations of LY294002 >/= 10 microM were cytostatic, but not
      cytotoxic, to cultures of the immortalized human breast epithelial cell line
      MCF10A-Neo. Treatment of MCF10A-Neo cultures with the AHR ligand 2,3,7,8
      tetrachlorodibenzo-p-dioxin (TCDD) stimulated the transcriptional activation of
      CYP1A1, as monitored by measurements of steady-state CYP1A1 mRNA. Pretreatment of
      cultures with >/= 10 microM LY294002 suppressed the TCDD activation of CYP1A1
      (IC(50) approximately 10 microM). Electrophoretic mobility shift assays employing
      rat liver cytosol demonstrated that concentrations of LY294002 </= 400 microM did
      not transform the AHR into a DNA-binding species. However, the addition of
      LY294002 to cytosol just prior to TCDD addition completely suppressed AHR
      transformation by TCDD (IC(50) approximately 35 microM). The PI 3-kinase
      inhibitor Wortmannin was weakly cytostatic, but not cytotoxic to MCF10A-Neo
      cultures at concentrations </= 500 nM. Exposure of cultures to Wortmannin (10-500
      nM) did not suppress TCDD activation of CYP1A1. Analyses of the phosphorylation
      status of Akt-1, an in vivo substrate of PI 3-kinase, demonstrated that
      concentrations of LY294002 >/= 50 microM and Wortmannin >/= 10 nM completely
      suppressed PI 3-kinase activity. Hence, the ability of LY294002 to suppress TCDD
      dependent activation of CYP1A1 is unrelated to PI 3-kinase inhibition. Instead,
      this activity reflects LY294002 functioning as an AHR antagonist. Furthermore,
      most of the cytostatic activity of LY294002 towards MCF10A-Neo cells is unrelated
      to the inhibition of PI 3-kinase.

PMID- 10927022
TI  - Specific induction of glutathione S-transferase GSTM2 subunit expression by
      epigallocatechin gallate in rat liver.
AB  - The antitumor effect of green tea polyphenols has been well characterized in
      numerous papers. However, the mechanism of their action is still poorly defined.
      In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea
      extract, was studied for its effect on the expression of glutathione S
      transferases (GSTs) in rat liver to examine the mechanism of action. Liver
      samples were collected from Sprague-Dawley rats treated with EGCG in H(2)O by
      portal vein perfusion and examined for total GST activity and GST expression. The
      results showed that the induction of GST activity by EGCG was dose- and time
      dependent. GST activity was increased about 28-fold at 12 hr after treatment.
      Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for
      changes in protein level affected by EGCG (1 mg/kg weight). Only GSTM2 revealed a
      significant time-dependent increase, with a maximal induction of approximately
      2.0-fold. The differential effect of EGCG on GST subunit expression was also
      verified by immunocytochemical examination and showed strong induction of the
      GSTM2 (but not the GSTA1/2 and GSTM1) level in liver section. This induction
      occurred as early as 3 hr after treatment and extended gradually outward from the
      hepatic veins as treatment time increased. The change in the GSTM2 protein level
      was accompanied by a corresponding alteration in mRNA quantity ( approximately
      2.0-fold of control). Our report is the first to demonstrate a specific induction
      of the GSTM2 subunit by a chemopreventor and suggests a primary influence of EGCG
      on GSTM2 gene expression.

PMID- 10927023
TI  - Inhibition of glucose transport and direct interactions with type 1 facilitative
      glucose transporter (GLUT-1) by etomidate, ketamine, and propofol: a comparison
      with barbiturates.
AB  - Ketamine, etomidate, propofol, and pentobarbital were compared for effects on and
      interactions with the type 1 facilitative glucose transporter (GLUT-1). Fluxes of
      radiolabeled hexoses were used to determine the effects of anesthetics on GLUT-1
      function. Hypotonic hemolysis of human erythrocytes was used to assess
      perturbations of membrane integrity. Quenching of intrinsic protein fluorescence
      was used to assess the direct interactions of anesthetics with purified GLUT-1.
      Pentobarbital, ketamine, etomidate, and propofol inhibited glucose transport in
      murine fibroblasts with IC(50) values of 0.8, 1. 6, 0.1, and 0.4 mM,
      respectively. Pentobarbital, ketamine, etomidate, and propofol also inhibited
      sugar transport in human erythrocytes. The IC(50) values for pentobarbital and
      ketamine exhibited substrate dependence for equilibrium exchange but not
      unidirectional effluxes. This was not observed for etomidate. Propofol did not
      inhibit equilibrium exchange but did inhibit unidirectional efflux with little
      substrate dependence. Pentobarbital protected against hemolysis, whereas
      etomidate and ketamine promoted hemolysis of erythrocytes. Propofol had no effect
      on membrane integrity. Pentobarbital, ketamine, and etomidate all interacted
      directly with GLUT-1, with apparent K(d) values of 2.2, 0.8, and 0.5 mM,
      respectively. Like barbiturates, ketamine, etomidate, and propofol inhibited GLUT
      1 at concentrations near to those used pharmacologically. Inhibition of GLUT-1 by
      these intravenous general anesthetics was complex, exhibiting differential
      kinetic effects on equilibrium exchange versus unidirectional fluxes and
      contrasting substrate dependencies. Like barbiturates, ketamine and etomidate
      bound to GLUT-1 with affinities that paralleled inhibition of glucose transport.
      As a class, intravenous general anesthetics, in contrast to inhalation
      anesthetics, inhibit GLUT-1-mediated glucose transport.

PMID- 10927024
TI  - Site-directed mutagenesis studies of human A(2A) adenosine receptors: involvement
      of glu(13) and his(278) in ligand binding and sodium modulation.
AB  - To provide insights into interactions between ligands and A(2A) adenosine
      receptors, site-directed mutagenesis was used to test the roles of a glutamic
      acid residue in the first transmembrane domain (Glu13) and a histidine residue in
      the seventh transmembrane domain (His278). The two residues, which have been
      suggested to be closely linked in molecular modeling studies, were mutated to
      glutamine (E13Q) and tyrosine (H278Y), respectively. Saturation experiments
      revealed that [(3)H]ZM241385 (4-2-[7-amino-2-(2-furyl)-1,2, 4-triazolo[1,5
      a][1,3,5]triazin-5-yl-amino]ethylphenol) bound wild-type and mutant receptors in
      membranes from COS-7 cells expressing human A(2A) adenosine receptors with high
      affinity and low non-specific binding. It was found from the competition
      experiments that the affinity of the A(2A) adenosine receptor agonists for the
      mutant receptors was 3- to 200-fold lower than for the wild-type receptor. Among
      antagonist competitors of binding at E13Q and H278Y mutant receptors, there was
      variation in the affinity depending on their different structures, although
      changes were relatively minor (<3-fold) except in the case of theophylline, whose
      affinity was decreased approximately 20 times on the H278Y mutant. The possible
      involvement of the two residues in sodium ion regulation was also tested. The
      agonist competition curves for [(3)H]ZM241385 were shifted to the right in both
      wild-type and mutant receptors in the presence of 1 M sodium ions, but the extent
      of shift (2- to 27-fold) in wild-type receptor was generally larger than for the
      mutant receptors. Sodium ions also decreased [(3)H]ZM241385 dissociation from
      both wild-type and mutant receptors, being more influential on the former than
      the latter. The results suggest that the two closely linked residues Glu13 and
      His278 in A(2A) adenosine receptor are most important for agonist recognition and
      are partly responsible for the allosteric regulation by sodium ions.

PMID- 10927025
TI  - Allosteric modulation of A(2A) adenosine receptors by amiloride analogues and
      sodium ions.
AB  - Allosteric regulation of rat A(2A) adenosine receptors by amiloride, amiloride
      analogues, and sodium ions was studied by investigating their ability to
      influence the dissociation of [(3)H]4-2-[7-amino-2-(2-furyl)-1,2,4-triazolo[1,5
      a][1,3, 5]triazin-5-yl-amino]ethylphenol ([(3)H]ZM241385) from receptors in rat
      striatal membranes. Both amiloride and its analogues accelerated the
      dissociation, the analogues being more potent than amiloride itself. In contrast,
      sodium ions decreased the rate of [(3)H]ZM241385 dissociation in a concentration
      dependent manner, and this rate was not influenced by guanosine triphosphate, N
      ethylmaleimide, suramin, or the selective A(2A) adenosine receptor antagonist, 5
      amino-2-(2-furyl)-7(2-phenylethyl)pyrazolo[4,3-e]-1,2, 4-triazolo[1,5
      c]pyrimidine (SCH58261). The effect of competition between the amiloride analogue
      5-(N,N-hexamethylene)amiloride (HMA) and sodium ions on [(3)H]ZM241385
      dissociation was also explored. The addition of sodium ions resulted in a
      concentration-dependent rightward shift of the HMA response curve. The slopes of
      the HMA concentration-response curves in the presence and absence of sodium ions
      were not significantly different, which suggests that sodium ions and amiloride
      analogues act at a common allosteric site on the A(2A) adenosine receptor. There
      was a lack of correlation between the displacement of ligand binding and the
      allosteric potencies of the amiloride analogues.

PMID- 10927026
TI  - Induction of apoptosis by a novel intestinal metabolite of ginseng saponin via
      cytochrome c-mediated activation of caspase-3 protease.
AB  - Ginseng saponins exert various important pharmacological effects with regard to
      the control of many diseases including cancer. The novel intestinal bacterial
      metabolites of ginseng protopanaxadiol saponins have recently been found and
      isolated after the oral administration of ginseng extract in human and rats. 20-O
      (beta-D-Glucopyranosyl)-20(S)-protopanaxadiol (IH-901) formed from ginsenosides
      Rb1, Rb2, and Rc is of particular interest in cancer chemoprevention and
      treatment. We investigated the effects of IH-901 on the human myeloid leukemia
      cell line HL-60 in terms of inhibition of proliferation and induction of
      apoptosis. IH-901 showed a significant cytotoxic activity in HL-60 cells (IC(50)
      = 24. 3 microM) following a 96-hr incubation. Treatment of HL-60 cells with IH
      901 resulted in the formation of internucleosomal DNA fragments. The dose- and
      time-dependent induction of apoptosis by IH-901 was demonstrated in sandwich
      enzyme immunoassay and the results were confirmed by flow cytometric analysis.
      Morphological examination of IH-901-treated samples showed cells with chromatin
      condensation, cell shrinkage, and nuclear fragmentation, all typical
      characteristics of apoptotic cells. The treatment of HL-60 cells with IH-901
      caused activation of caspase-3 protease and subsequent proteolytic cleavage of
      poly(ADP-ribose) polymerase. IH-901 did not affect the expression of
      antiapoptotic protein Bcl-2 but did cause a release of mitochondrial cytochrome c
      into cytosol. In conclusion, our results demonstrate that IH-901 dramatically
      suppresses HL-60 cell growth by inducing programed cell death through activation
      of caspase-3 protease, which occurs via mitochondrial cytochrome c release
      independently of Bcl-2 modulation. These results may provide a pivotal mechanism
      for the use of IH-901 in the prevention and treatment of leukemia.

PMID- 10927027
TI  - Effect of administration of 5-(phenylselenenyl)acyclouridine, an inhibitor of
      uridine phosphorylase, on the anti-tumor efficacy of 5-fluoro-2'-deoxyuridine
      against murine colon tumor C26-10.
AB  - The effect of co-administration of 5-(phenylselenenyl)acyclouridine (PSAU), a new
      uridine phosphorylase (UrdPase, EC 2.4.2.3) inhibitor, on the efficacy of 5
      fluoro-2'-deoxyuridine (FdUrd) was tested against murine colon C26-10 tumor
      xenografts. In contrast to our previous results with human tumors, co
      administration of PSAU with FdUrd decreased instead of increasing the efficacy of
      FdUrd against tumor growth. However, co-administration of PSAU with FdUrd (300
      mg/kg/day) protected the mice completely from the 83% mortality induced by the
      same dose of FdUrd alone. Enzyme studies indicated that UrdPase in colon C26-10
      tumors is responsible for the catabolism of FdUrd to 5-fluorouracil (FUra), as
      colon C26-10 tumors do not have thymidine phosphorylase (dThdPase, EC 2.4.2.4).
      In contrast, colon C26-10 tumors had extraordinarily high UrdPase activity (300
      micromol/min/mg protein), which was at least 200-fold higher than the highest
      UrdPase activity in any of the human xenografts we tested previously.
      Furthermore, the activities of UrdPase and orotate phosphoribosyltransferase
      (OPRTase, EC 2.4.2.10) were 192- and 2-fold higher, respectively, while that of
      dihydrouracil dehydrogenase (EC 1.3.1.2) was 1000-fold lower in the tumor than in
      the host liver. It is suggested that FdUrd exerts its anticancer effects against
      colon C26-10 tumors mainly through the catabolism of FdUrd to FUra by UrdPase,
      which then could be anabolized to 5-fluorouridine 5'-monophosphate (FUMP) by
      OPRTase and ultimately to other toxic 5-fluorouridine nucleotides, hence inducing
      the observed FdUrd toxic effects. Co-administration of PSAU with FdUrd inhibited
      UrdPase and the catabolism of FdUrd to FUra. This would result in the observed
      reduction of the antitumor efficacy of FdUrd. In addition, the increase in plasma
      uridine concentration induced by PSAU as well as the catabolism of FUra by the
      high dihydrouracil dehydrogenase activity in the liver also may have circumvented
      any residual FUra toxic effects against the host. These results clearly
      demonstrate that the anticancer efficacy of the combination of UrdPase inhibitors
      and FdUrd is not general and is dependent largely on the type of tumor under
      treatment and the mode of FdUrd metabolism in these tumors.

PMID- 10927028
TI  - Inhibition of neuronal nitric oxide synthase activity by 3-[2-[4-(3-chloro-2
      methylphenyl)- 1-piperazinyl]ethyl]-5, 6-dimethoxy-1-(4-imidazolylmethyl)-1H
      indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel neuroprotective agent,
      in vitro and in cultured neuroblastoma cells in situ.
AB  - DY-9760e, 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5, 6-dimethoxy-1
      (4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate, a novel calmodulin
      (CaM) antagonist, possesses neuroprotective activity. In the current study, we
      examined the effects of DY-9760e on nitric oxide synthase (NOS) activities in
      vitro and on calcium ionophore-induced NO production in situ. DY-9760e inhibited
      both neuronal NOS and endothelial NOS activities without affecting inducible NOS
      activity. It also inhibited purified neuronal NOS activity with a potency similar
      to that seen for purified CaM kinase II activity in vitro. Furthermore, DY-9760e
      significantly inhibited Ca(2+) ionophore (A23187)-induced NO production in mouse
      N1E-115 neuroblastoma cells, at a concentration of less than 1 microM. In
      contrast, no apparent inhibitory effect on Ca(2+)/CaM-dependent protein kinase II
      activity was observed in cultured hippocampal neurons up to 5 microM. These
      results suggest that the inhibitory effect of DY-9760e on CaM-dependent NOS
      activities underlies neuroprotective effects of the agent.

PMID- 10927029
TI  - Comparison of the relative effects of 1,24-dihydroxyvitamin D(2) [1, 24
      (OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25
      dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on selected vitamin D-regulated events
      in the rat.
AB  - The present experiments were conducted to compare the relative hypercalciuric and
      hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24
      dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25
      (OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for
      7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the
      three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D
      24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite
      levels, and on the capacity to evoke modification in the vitamin D
      receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma
      calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25
      (OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was
      elevated significantly (relative to controls) in all groups. The order of
      hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24
      (OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was
      elevated to a similar extent in all groups relative to controls. Duodenal 24
      hydroxylase mRNA was elevated in all groups relative to controls; however, the
      elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25
      (OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24
      hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25
      (OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats.
      Recombinant human vitamin D receptor (hVDR) extracts were incubated with
      saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25
      (OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay
      (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24
      (OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24
      (OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR
      conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as
      either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria
      in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological
      responses similar to the vitamin D(3) sterols. These different responses may be
      related to the alterations in conformation state of the hVDR/hRXR heterodimer.

PMID- 10927030
TI  - Antioxidant activity of the monoamine oxidase B inhibitor lazabemide.
AB  - Free radical-induced damage to lipid and protein constituents of neuronal
      membranes contributes to the pathophysiology of neurodegenerative diseases,
      including Alzheimer's disease (AD). The development of an effective inhibitor of
      oxidative stress represents an important goal for the treatment of AD. In this
      study, the intrinsic antioxidant activity of lazabemide, a potent and reversible
      inhibitor of monoamine oxidase B (MAO-B), was tested in a membrane-based model of
      oxidative stress. Under physiologic-like conditions, lazabemide inhibited lipid
      peroxidation in a highly concentration-dependent manner. At low, pharmacologic
      levels of lazabemide (100.0 nM), there was a significant (P < 0.001) and
      catalytic reduction in lipid peroxide formation, as compared with control
      samples. The antioxidant activity of lazabemide was significantly more effective
      than that of either vitamin E or the MAO-B inhibitor, selegiline. The ability of
      lazabemide to inhibit oxidative damage is attributed to physico-chemical
      interactions with the membrane lipid bilayer, as determined by small angle x-ray
      diffraction methods. By partitioning into the membrane hydrocarbon core,
      lazabemide can inhibit the propagation of free radicals by electron-donating and
      resonance-stabilization mechanisms. These findings indicate that lazabemide is a
      potent and concentration-dependent inhibitor of membrane oxy-radical damage as a
      result of inhibiting membrane lipid peroxidation, independent of MAO-B
      interactions.

PMID- 10927031
TI  - Inhibition of nuclear factor-kappab activation in mouse macrophages and the RAW
      264.7 cell line by a synthetic adenyl carbocyclic nucleoside.
AB  - Adenyl carbocyclic nucleosides have potent anti-inflammatory effects on a number
      of cell types. Notable in this regard is their ability to inhibit the production
      of tumor necrosis factor-alpha (TNF-alpha) by mouse macrophages that have been
      activated with bacterial lipopolysaccharide (LPS). Because the transcriptional
      activation of the mouse TNF-alpha gene is highly dependent on kappaB enhancers,
      the present study determined whether the synthetic carbocyclic nucleoside 9
      [(1S,3R)-cis-cyclopentan-3-ol]adenine (cPA) inhibited LPS-induced nuclear factor
      kappaB (NF-kappaB) activation in these cells. Stimulation of either mouse
      peritoneal macrophages or RAW 264. 7 macrophage-like cells with LPS led to the
      appearance of four distinct kappaB-binding nucleoprotein complexes detected by
      gel mobility shift assays. Cells treated with 100 microM cPA showed significantly
      reduced levels of NF-kappaB activation as evidenced by measurements of
      nucleoprotein kappaB-binding activity and diminished kappaB-dependent
      transcriptional activation. However, both the LPS-induced degradation of the
      cytoplasmic NF-kappaB inhibitor IkappaBalpha and the nuclear translocation of the
      NF-kappaB p50, p65, and c-Rel peptides were unaffected by treatment of the cells
      with the nucleoside. These findings suggest that certain adenyl carbocyclic
      nucleosides inhibit the activation of NF-kappaB/Rel complexes by a novel
      mechanism that results in an inhibition of their DNA-binding activities, without
      blocking their dissociation from IkappaBalpha or their nuclear translocation.

PMID- 10927032
TI  - Inhibition of C5a-induced neutrophil chemotaxis and macrophage cytokine
      production in vitro by a new C5a receptor antagonist.
AB  - A cyclic peptide, Phe-[Orn-Pro-D-Cyclohexylalanine-Trp-Arg] (F-[OPdChaWR]), was
      recently shown in vitro to antagonise the binding of C5a to its receptor (CD88)
      on human polymorphonuclear leukocytes (PMNs) and in vivo to inhibit the
      neutropenia associated with septic shock induced by lipopolysaccharide (LPS) in
      rats. The aim of this study was to investigate whether F-[OPdChaWR] inhibits C5a
      mediated chemotaxis of human PMNs using a modified Boyden chamber and C5a
      stimulated release of cytokines from human monocytes in vitro. Approximately 50%
      of the chemotactic activity induced by 10 nM C5a was inhibited by 76 nM F
      [OPdChaWR]. This correlated with inhibition of C5a-induced polarisation of PMNs
      by F-[OPdChaWR]. C5a alone failed to induce release of the inflammatory cytokines
      interleukin(IL)-1beta, tumour necrosis factor (TNF)-alpha, and IL-6 from human
      monocytes at concentrations up to 100 nM. However, in the presence of low
      concentrations of LPS (50 ng/mL), both IL-1beta and TNF-alpha were stimulated by
      1 nM C5a. This co-stimulation was inhibited by F-[OPdChaWR] with IC(50)s of 0.8
      and 6.9 nM for release of TNF-alpha and IL-1beta, respectively. No agonist
      activity was detected for F-[OPdChaWR] in either the chemotaxis or cytokine
      release assays at concentrations up to 50 microM. These results show that F
      [OPdChaWR] inhibits several important inflammatory activities of C5a and suggest
      that C5a receptor antagonists may be effective in the treatment of inflammatory
      diseases mediated by C5a.

PMID- 10927033
TI  - Use of fibrinolytic agents in the prevention of postoperative adhesion formation.
AB  - OBJECTIVE: To review the events leading to the formation of adhesions, to
      describe the development of fibrinolytic agents, to review more than a century of
      research on the use of fibrinolytic agents in adhesion prevention, and to look at
      future aspects of adhesion prevention. RESULTS: A better understanding of the
      pathogenesis of adhesion formation has resulted in the use of fibrinolytic agents
      in their prevention. Fibrinolytic agents promote fibrinolytic activity during the
      early period after peritoneal trauma during which an increased formation of
      fibrin is seen in combination with a deficiency of endogenous fibrinolytic
      activity. Initially, chemical attacks on fibrin (fibrolysin and hypertonic
      glucose), foreign digestive ferments (pepsin, trypsin, and papain), and
      stimulation of intraperitoneal leukocytosis (amniotic fluid) were used.
      Development of new thrombolytic agents was soon followed by experiments in animal
      adhesion models and clinical studies to examine their antiadhesion properties.
      Plasmin preparations (plasmin, actase, and fibrinolysin) and plasmin activators
      (streptokinase, urokinase, and tissue-type plasminogen activator) were found to
      be efficacious in preventing adhesion formation in the greater part of reviewed
      animal and clinical studies. CONCLUSION(S): From the current literature, it can
      be concluded that postoperative intraperitoneal administration of thrombolytic
      agents can significantly decrease adhesion formation. Given the large number of
      experimental studies in animals, future studies should focus on the clinical use
      of fibrinolytic agents in the prevention of postsurgical adhesion formation.

PMID- 10927034
TI  - Disposition of extra embryos.

PMID- 10927035
TI  - Necrospermia and chronic spinal cord injury.
AB  - OBJECTIVE: To determine whether improvement in quality of semen over 4
      consecutive days of electroejaculation in men with chronic spinal cord injury
      (SCI) was consistent with epididymal necrospermia. DESIGN: Prospective study of a
      random sample of men with SCI. SETTING: A southeastern Australian SCI management
      center in collaboration with the specialist andrology service of a university
      based department of obstetrics and gynecology in a tertiary referral hospital.
      PATIENT(S): Nine men with chronic spinal cord injury. INTERVENTION(S): Semen
      samples were obtained by using electroejaculation, and testicular biopsy samples
      were obtained by using fine-needle tissue aspiration. MAIN OUTCOME MEASURE(S):
      Semen analysis was performed according to World Health Organization criteria.
      Testicular biopsy and electron microscopy were done by using standard techniques.
      RESULT(S): During up to 4 days of consecutive-day electroejaculation, sperm
      motility and viability in semen obtained from men with chronic SCI increased by
      an average of 23% on days 2 and 3. The severity of the degenerative changes and
      the numbers of spermatozoa affected on day 1 became less marked by day 4. The
      changes were not present in late spermatids obtained from testicular biopsies.
      CONCLUSION(S): The asthenospermia of chronic SCI is similar to epididymal
      necrospermia and can be improved by consecutive-day electroejaculation.

PMID- 10927036
TI  - Evaluation of meiotic impairment of azoospermic men by fluorescence in situ
      hybridization.
AB  - OBJECTIVE: To identify predictive criteria for the existence of spermatogenesis
      in nonobstructive azoospermic men. DESIGN: Prospective study. SETTING: Andrology
      laboratory at a teaching hospital. PATIENT(S): Twenty-two azoospermic men were
      divided into three groups by qualitative testicular histopathology and the
      presence of spermatozoa in minced biopsies. INTERVENTION(S): Testicular biopsies
      evaluation. MAIN OUTCOME MEASURE(S): The presence of spermatozoa and/or mature
      spermatids, the percentage of sex vesicle formation (X and Y chromosomes in
      proximity), and the pairing of the two 18 homologous chromosomes. RESULT(S):
      Spermatozoa and mature spermatids were found in 17 study patients. Whenever few
      mature spermatids and/or spermatozoa were found, the rates of X-Y and 18
      bivalents were significantly higher (mean +/- SD, 73% +/- 13. 3% and 91% +/-
      7.1%) than those in cases of spermatocyte maturation arrest (23% +/- 8.0% and 60%
      +/- 11.8%, respectively). CONCLUSION(S): Pairing of chromosomes during meiosis is
      apparently related to the progression of spermatogenesis. Consequently, high
      rates of bivalent formation increase the prospect of focal spermatogenesis in the
      testis, despite the failure to identify mature spermatids in the specific
      testicular biopsy under examination.

PMID- 10927037
TI  - Serum inhibin B levels in males with gonadal dysfunction.
AB  - OBJECTIVE: To determine whether inhibin B levels are reflective of the etiology
      of gonadal dysfunction. DESIGN: Institutional study. SETTING: A tertiary care
      university-affiliated infertility clinic. PATIENT(S): Forty-four men: 16 with
      primary testicular failure, 10 with partial idiopathic hypogonadotropic
      hypogonadism (IHH), 8 with primary germ cell failure, one with iatrogenic
      hypogonadotropic hypogonadism, one with untreated Kallmann's syndrome, and 8
      healthy fertile controls. INTERVENTION(S): Three individuals (one each with IHH,
      hypogonadotropic hypogonadism [HH], and Kallmann's syndrome) underwent treatment
      with human chorionic gonadotropin. MAIN OUTCOME MEASURE(S): Baseline serum
      inhibin B, FSH, LH, total testosterone and estradiol levels, and sperm
      concentrations were measured. RESULT(S): Serum inhibin B concentrations were
      significantly higher in fertile controls (255 +/- 59 pg/mL) than in men
      presenting with primary testicular failure (75 +/- 46 pg/mL, P<.0001) or in those
      presenting with primary germ cell failure (73 +/- 31 pg/mL, P<.0001). Inhibin B
      levels were also lower in males with partial IHH (187 +/- 112 pg/mL, P<.05). The
      patient with iatrogenic HH had a level of 184 pg/mL, whereas the patient with
      Kallmann's syndrome had nondetectable levels (<10 pg/mL). Serum inhibin B levels
      correlated positively with sperm concentration (P=.0001), and negatively with FSH
      levels (P=.01) and LH levels (P<.05). Human chorionic gonadotropin therapy
      altered inhibin B levels. CONCLUSION(S): Inhibin B plays an important role as an
      endocrine regulator of FSH secretion, whereas gonadotropins are involved in the
      regulation of inhibin B secretion.

PMID- 10927038
TI  - Human testicular mast cells contain tryptase: increased mast cell number and
      altered distribution in the testes of infertile men.
AB  - OBJECTIVE: To determine whether human testicular mast cells contain the potent
      fibroblast growth factor tryptase and to examine changes in mast cell morphology
      and intratesticular distribution in testes with normal spermatogenesis versus
      abnormal spermatogenesis. DESIGN: Retrospective evaluation of testicular biopsies
      with the use of immunohistochemistry, morphometry, and electron microscopy.
      SETTING: University research and clinical institutes. PATIENT(S): Infertile men
      (total of 24) with severe hypospermatogenesis, germ cell arrest syndrome, or
      Sertoli cell only syndrome, and men without pathologies. INTERVENTION(S):
      Diagnostic testicular biopsy. MAIN OUTCOME MEASURE(S): Location, number, and
      distribution of testicular mast cells. RESULT(S): All groups showed tryptase
      positive mast cells. In specimens with normal spermatogenesis, mast cells were
      round and located mainly in the interstitial spaces close to Leydig cells. In
      germ cell arrest syndrome, a 2-fold increase was evident, and in Sertoli cell
      only syndrome, a >3-fold increase of tryptase-immunoreactive mast cells became
      evident. Moreover, there was a statistically significant shift of the cells from
      the interstitium to the tubular walls in Sertoli cell only syndrome and germ cell
      arrest syndrome. Mast cells in specimens of Sertoli cell only syndrome and germ
      cell arrest syndrome were heterogeneous, with rounded or elongated shapes and
      signs of degranulation. The thickness of the tubular walls was doubled in
      specimens of germ cell arrest syndrome and Sertoli cell only syndrome in
      comparison with normal specimens, and this increase was positively correlated
      with the number of mast cells in these patients. CONCLUSION(S): Our results
      suggest that mast cell products, including the potent fibroblast growth factor
      tryptase, are involved in the thickening of the tubular wall and other changes in
      infertile testes.

PMID- 10927039
TI  - Measuring apoptosis in human spermatozoa: a biological assay for semen quality?
AB  - OBJECTIVE: [1] To determine whether apoptosis can be measured in ejaculated
      spermatozoa by flow cytometry using the Annexin V assay, which measures
      expression of phosphatidylserine on the outer leaflet of the cell membrane, or
      the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP [deoxy-uridine
      triphosphate] nick end labeling) assay, which measures occurrence of DNA strand
      breaks and [2] to correlate the outcome with routine semen variables and the
      hypoosmotic swelling (HOS) test. DESIGN: Pilot study and clinical trial. SETTING:
      Large teaching hospital and fertility center. PATIENT(S): Men whose semen was
      studied for various reasons. MAIN OUTCOME MEASURE(S): Percentage of apoptotic
      spermatozoa by two different assays, percentage of necrotic spermatozoa,
      concentration and motility of spermatozoa, and outcome of the HOS test.
      RESULT(S): Apoptosis can be measured in spermatozoa by flow cytometry using the
      Annexin V assay and the TUNEL assay. Twenty percent of spermatozoa were apoptotic
      according to both assays. A significant inverse correlation was seen between
      phosphatidylserine expression (Annexin V assay) and sperm concentration (r = 
      0.389; P<.05) and motility (r = -0.289; P<.05). A highly significant inverse
      correlation was seen between DNA double-strand breaks (TUNEL assay) and sperm
      concentration (r = -0.629; P<.0001). CONCLUSION(S): Flow cytometry can easily and
      reliably detect phosphatidylserine expression on the outer leaflet of the cell
      membrane and DNA strand breaks, both of which are hallmarks of apoptosis. About
      20% of ejaculated spermatozoa are apoptotic, and the concentration of spermatozoa
      is lower in men with more apoptotic spermatozoa.

PMID- 10927040
TI  - Role of mitotic control in spermatogenesis.
AB  - OBJECTIVE: To study the correlation between the incidence of sex chromosome
      aneuploidies in the somatic cells and spermatozoa in karyotypically normal
      infertile men and fertile donors. DESIGN: A prospective, phase two, controlled
      study. SETTING: A teaching Hospital Reproductive Medicine and Medical Genetics
      Units. PATIENT(S): Ten patients with idiopathic oligozoospermia and 10 sperm
      donors with proven fertility, all with a normal karyotype 46, XY.
      INTERVENTION(S): Multicolor fluorescence in situ hybridization (FISH) of
      peripheral blood lymphocytes and spermatozoa using a probe cocktail containing
      the alpha satellite DXZ1 for the X centromere, DYZ1 for the heterochromatic
      region of the long arm of the Y, and cosmids D21S259, D21S341, and D21S342 for
      Down syndrome critical region of chromosome 21. MAIN OUTCOME MEASURE(S): The
      incidence of chromosome X, Y, and 21 aneuploidies in peripheral lymphocytes and
      spermatozoa in both groups. RESULT(S): The incidence of aneuploidies related to
      chromosomes X, Y, and 21 were significantly higher in peripheral lymphocytes and
      spermatozoa of infertile men compared with donors. There was a positive
      correlation between the incidence of chromosome aneuploidies in the somatic cells
      and sperm in all men. CONCLUSION(S): These findings provide suggestive evidence
      for the importance of mitosis in spermatogenesis and the role of mitotic
      instability in unexplained oligozoospermia.

PMID- 10927041
TI  - Platelet-activating factor content in human spermatozoa and pregnancy outcome.
AB  - OBJECTIVE: To determine whether platelet-activating factor (PAF) content in human
      spermatozoa from an isolated population is related to fertilization and pregnancy
      outcome. DESIGN: Prospective analysis of PAF content in human spermatozoa after a
      Percoll gradient wash and its relation to fertilization and pregnancy outcome.
      SETTING: University-based reproductive genetics laboratory. SUBJECT(S): Couples
      undergoing assisted reproduction. INTERVENTION(S): Lipids extracted from Percoll
      gradient spermatozoa were quantitated for PAF content by a specific
      radioimmunoassay. MAIN OUTCOME MEASURE(S): The relation between spermatozoa
      derived PAF levels and motility, concentration, morphology, and fertilization and
      pregnancy rates were determined by using regression analysis and the Student t
      test. RESULT(S): Radioimmunoassay and regression analysis showed a significant
      and positive relation between PAF content in human spermatozoa and concentration
      and motility indices and implantation rate. Patients who became pregnant had a
      significantly higher PAF content in the spermatozoa used (7.285 pmol/10(6) cells)
      than did patients who did not become pregnant (2.990 pmol/10(6) cells).
      CONCLUSION(S): The PAF content in human spermatozoa has a significant and
      positive relation with motility and concentration indices and implantation rate.
      Pregnancy rates but not fertilization rates may be predicted by measuring PAF
      levels in an isolated subpopulation of human spermatozoa.

PMID- 10927042
TI  - Hormone replacement therapy reverses the decrease in natural killer cytotoxicity
      but does not reverse the decreases in the T-cell subpopulation or interferon
      gamma production in postmenopausal women.
AB  - OBJECTIVE: To investigate the immunologic deviations of postmenopausal women
      before and after hormone replacement therapy (HRT). DESIGN: Prospective study.
      SETTING: University teaching hospital. PATIENT(S): Seventeen postmenopausal women
      (study group) and 17 women of reproductive age (control group). INTERVENTION(S):
      Continuous usage of E(2) valerate 2 mg/d and medroxyprogesterone acetate 5 mg/d
      in postmenopausal women in the study group. MAIN OUTCOME MEASURE(S):
      Immunophenotyping with flow cytometry, cytokine production with and without
      mitogen stimulation of the peripheral mononuclear cells, and a natural killer
      (NK) cell cytotoxicity test against K562 target cells by the (51)Cr-release assay
      were performed in the control group and in the study group before, 1 month after,
      and 6 months after HRT. RESULT(S): NK cytotoxicity, interferon-gamma production,
      and the T-cell subpopulation were significantly decreased, and the subpopulations
      of CD3(+)CD25(+) and CD3(+)HLA-DR(+) were increased in the study group before HRT
      when compared with those in the control group. After HRT was given for 6 months,
      however, the NK cytotoxicity increased significantly in the postmenopausal women
      to a value similar to that of the control group. CONCLUSION(S): Women after
      menopause are prone to impaired immune responses. Nevertheless, some of the
      impairment can be restored after HRT.

PMID- 10927043
TI  - Venous endothelial function in postmenopausal women who are receiving long-term
      estrogen and progestagen therapy.
AB  - OBJECTIVE: To test venous endothelial function during long-term hormone
      replacement therapy (HRT) and after treatment withdrawal. DESIGN: Measurement of
      dorsal hand-vein diameter by venous occlusion plethysmography during infusion of
      norepinephrine, bradykinin, NG-monomethyl L-arginine, and sodium nitroprusside.
      SETTING: Plethysmography and menopause units, University Hospital Marques de
      Valdecilla, Santander, Spain. PATIENT(S): Twenty postmenopausal women, of whom 10
      were assigned to receive no hormone replacement therapy (HRT) for 6 months after
      plethysmography (group A) and 10 were assigned to receive HRT for 6 months (group
      B). After 6 months, HRT was administered to group A and withdrawn from group B
      for another 6 months. INTERVENTION(S): Plethysmography at baseline and at 6 and
      12 months. MAIN OUTCOME MEASURE(S): Dorsal hand-vein diameter measured by venous
      occlusion plethysmography during infusion of norepinephrine, bradykinin, NG
      monomethyl L-arginine, or sodium nitroprusside. RESULT(S): At 6 months, the
      maximum dilation obtained with bradykinin was 48.8 +/- 7.58% in group A and 76.7
      +/- 12.9% in group B. At 12 months, maximum bradykinin dilation increased to 74.3
      +/- 14.2% in group A and decreased to 54.0 +/- 15.9% in group B. CONCLUSION(S):
      Long-term HRT with estrogen plus progestin improves endothelium-dependent
      vasodilation, but this effect is lost in a relatively short time. Endothelial
      function in dorsal hand veins is an easy-to-use plethysmography model that can be
      used in serial studies.

PMID- 10927044
TI  - New look at endometrial echogenicity: objective computer-assisted measurements
      predict endometrial receptivity in in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To determine whether endometrial echogenicity, assessed objectively by
      a computer-assisted system on the day of hCG administration, predicts endometrial
      receptivity in controlled ovarian hyperstimulation (COH) cycles for IVF-ET.
      DESIGN: Prospective analysis. SETTING: Assisted reproduction unit, Clamart,
      France. PATIENT(S): Two hundred twenty-one women (aged <38 years with a normal
      uterus and >/=2 grade A or B embryos transferred) undergoing 228 GnRH agonist and
      FSH/hCG cycles for IVF-ET. INTERVENTION(S): On the day of hCG administration,
      uterine ultrasound scans were digitized with an image analysis system.
      Endometrial echogenicity was assessed as the ratio of the extent of the
      hyperechogenic transformation over the whole endometrial thickness. According to
      this, cycles were sorted arbitrarily into six groups: <30% (n = 34), 31%-40% (n =
      37), 41%-50% (n = 37), 51%-60% (n = 55), 61%-70% (n = 37), and >70% (n = 28).
      MAIN OUTCOME MEASURE(S): Pregnancy and implantation rates. RESULT(S): The groups
      were similar in regard to population characteristics, ovarian response to COH,
      and embryology data. Pregnancy rates (59%, 57%, 35%, 20%, 16%, and 11%,
      respectively) and implantation rates (35%, 23%, 17%, 6%, 7%, and 3%,
      respectively) fell progressively and significantly from the low-echogenicity
      group to the high-echogenicity group. CONCLUSION(S): The present results confirm
      and extend previous observations that advanced hyperechogenic transformation of
      the endometrium is associated with poor IVF-ET outcome.

PMID- 10927045
TI  - Blastocyst quality affects the success of blastocyst-stage embryo transfer.
AB  - OBJECTIVE: To determine the relationship between blastocyst quality and the
      results of embryo transfer at the blastocyst stage. DESIGN: Retrospective case
      analysis. SETTING: Tertiary care private hospital IVF center. PATIENT(S): A total
      of 350 blastocyst-stage embryo transfer cycles. INTERVENTION(S): In vitro culture
      to the blastocyst stage was undertaken in 350 ICSI cycles where four or more
      cleavage-stage embryos were available on day 3. MAIN OUTCOME MEASURE(S):
      Relationship between blastocyst quality and implantation and clinical and
      multiple pregnancy rates. RESULT(S): Transfer of at least one grade 1 or grade 2
      blastocyst or one hatching blastocyst was associated with very high implantation
      and pregnancy rates. However, transfer of grade 3 blastocysts yielded very low
      implantation and pregnancy rates. CONCLUSION(S): There appears to be a strong
      correlation between blastocyst quality and success of blastocyst transfer.

PMID- 10927046
TI  - Does assisted hatching pose a risk for monozygotic twinning in pregnancies
      conceived through in vitro fertilization?
AB  - OBJECTIVE: To examine the association between assisted hatching and monozygotic
      (MZ) twinning. DESIGN: Case-control. SETTING: Population-based sample of IVF-ET
      cycles initiated in U.S. clinics, 1996. PATIENT(S): The IVF-ET (n = 35,503)
      cycles and 11,247 resultant pregnancies. INTERVENTION(S): Use of an assisted
      hatching procedure on embryos transferred. MAIN OUTCOME MEASURE(S): Cases were
      pregnancies for which number of fetal hearts observed on ultrasound exceeded
      number of embryos transferred. These pregnancies were considered to contain at
      least one MZ set of twins. Cases were compared with two control groups: other
      multiple-gestation pregnancies (>/=2 fetal hearts but number of fetal hearts </=
      number of embryos transferred); and singleton pregnancies (1 fetal heart).
      RESULT(S): Women with a case pregnancy were more likely to have received embryos
      treated with assisted hatching procedures than were women in either control
      group. After adjustment for patient age, number of embryos transferred, prior
      cycles, infertility diagnosis, intracytoplasmic sperm injection, and whether
      embryos from the current cycle were cryopreserved for later use, odds ratios and
      95% CIs for use of assisted hatching were 3.2 (1.2-8.0), compared with other
      multiple-gestation pregnancies, and 3.8 (1.8-9.8), compared with singleton
      pregnancies. CONCLUSION(S): Assisted hatching may pose a risk for MZ twinning.

PMID- 10927047
TI  - Nuclear status and cytogenetics of embryos derived from in vitro-matured oocytes.
AB  - OBJECTIVE: To analyze embryos after in vitro maturation by investigating their
      nuclear status and cytogenetic constitution. DESIGN: Prospective randomized
      laboratory study. SETTING: Reproductive medicine unit in an academic hospital.
      PATIENT(S): Patients with male and tubal factor infertility undergoing fertility
      treatment. INTERVENTION(S): Denuded immature oocytes (n = 75) were matured in
      vitro for 24-30 hours, and intracytoplasmic sperm injection was performed 30
      hours after oocyte retrieval. Fluorescence in situ hybridization was performed on
      the produced embryos. MAIN OUTCOME MEASURE(S): Blastomere content of the total
      embryo. RESULT(S): The in vitro-matured oocytes showed a similar fertilization
      rate as the in vivo-matured oocytes, but with a higher incidence of noncleavage
      (21.0%). In addition, 26.7% of these embryos arrested at the first mitotic
      division. Thirty embryos were processed for fluorescence in situ hybridization;
      only 6.7% had all mononuclear blastomeres, 30.0% had at least one binuclear
      blastomere, 43.3% had at least one multinuclear blastomere, and 56.6% contained
      anuclear cells. The chromosomal constitution was analyzed in 14 embryos, and
      chromosomal anomalies were found in 11 (78.5%). CONCLUSION(S): Germinal vesicle
      oocytes retrieved from superovulated patients and cultured in vitro for a short
      time had the ability to resume meiosis and achieve fertilization. However, arrest
      of embryo development was common. These embryos showed a high incidence of
      multinuclear blastomeres and aneuploidy, suggesting abnormal cytokinesis or
      genetic abnormalities.

PMID- 10927048
TI  - A crossover study of triptorelin and leuprorelin acetate.
AB  - OBJECTIVE: To compare the potency, side effects, and duration of action of
      triptorelin and leuprorelin acetate after i.m. injections. DESIGN: Prospective,
      double-blind crossover clinical study. SETTING: A teaching hospital. PATIENT(S):
      Fifty-four patients with pelvic endometriosis. INTERVENTION(S): Twenty-seven
      patients had three doses of i.m. triptorelin (3.75 mg) followed by three doses of
      i.m. leuprorelin acetate at 4-week intervals. Twenty-one patients had three doses
      of i.m. leuprorelin acetate (3.75 mg) followed by three doses of i.m.
      triptorelin, also at 4-week intervals. MAIN OUTCOME MEASURE(S): Menopausal
      symptoms, time taken for menstruation to return, serum E(2), FSH, LH levels,
      lipid profiles, and liver function tests. RESULT(S): The potencies of triptorelin
      and leuprorelin acetate in lowering the serum E(2), FSH, and LH levels were
      comparable. The severity of menopausal symptoms, changes in the lipid profile and
      liver function parameters were similar after triptorelin and leuprorelin acetate.
      The resurgence of ovarian activities and the spontaneous return of menstruation
      occurred significantly earlier after leuprorelin acetate than triptorelin.
      CONCLUSION(S): Both drugs are equally potent in down-regulating the pituitary
      ovarian function, and their side effects are similar. Triptorelin has a longer
      duration of drug action and can be administered over a longer interval period.

PMID- 10927049
TI  - Early-stage endometriosis: adhesion and growth of human menstrual endometrium in
      nude mice.
AB  - OBJECTIVE: To evaluate the implantation of menstrual endometrium and the early
      stages of evolution of endometriotic lesions. DESIGN: Experimental prospective
      study. SETTING: An academic research environment. ANIMALS: Ten nude mice.
      INTERVENTION(S): A minilaparotomy was performed to place fresh human menstrual
      endometrial samples in the peritoneal cavity. Removal of the transplants was
      performed successively on days 1, 3, and 5 by laparotomy. MAIN OUTCOME
      MEASURE(S): Adhesion of endometrial fragments and early stages of endometrial
      lesions was morphologically and immunohistochemically studied. RESULT(S): As
      early as day 1, stromal cells were found to be attached to the mesothelium. A
      progressive reorganization of epithelial and stromal cells into endometrial
      glands was observed. On day 5, cystic endometriotic lesions were characterized by
      more extensive proliferative activity in glandular cells and a higher VEGF score
      in stromal cells than that observed in previously removed transplants.
      CONCLUSION(S): Menstrual human endometrium is able to implant on intact
      mesothelium and to reorganize itself into structured glands and stroma under the
      influence of unknown factors. We suggest that stromal and glandular cells have
      two distinct roles: stromal cells are involved in the attachment process and
      glandular cells in the growth of the endometriotic lesion.

PMID- 10927050
TI  - Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium
      in endometriosis and adenomyosis.
AB  - OBJECTIVE: To determine the expression of glutathione peroxidase (GPx) in the
      eutopic and ectopic endometria during the menstrual cycle in endometriosis and
      adenomyosis. DESIGN: Immunohistochemical identification of GPx in endometrial
      tissues identified using the polyclonal antibody. SETTING: Department of
      obstetrics and gynecology in a university hospital. PATIENT(S): One hundred
      fourteen women divided into three groups: 33 patients with endometriosis, 34
      patients with adenomyosis, and 47 fertile control subjects. INTERVENTION(S):
      Endometrium biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S):
      Endometrial cells: semiquantitative immunostaining (evaluation nomogram) score.
      RESULT(S): The analyses revealed phase-dependent changes of GPx expression in the
      surface and glandular epithelia in the eutopic endometrium during the menstrual
      cycle in the fertile controls, i.e., the expression was weak in the early
      proliferative phase, gradually increased, was most marked in the early secretory
      phase, and decreased thereafter. The expression of GPx in the eutopic endometrium
      in endometriosis lost the variation during the menstrual cycle. The expression of
      GPx in adenomyosis was persistently marked over the control levels throughout the
      menstrual cycle. CONCLUSION(S): The aberrant expression of GPx in the eutopic
      endometrium throughout the cycle suggests a pathological role in endometriosis
      and adenomyosis.

PMID- 10927051
TI  - The alternating-sequence design (or multiple-period crossover) trial for
      evaluating treatment efficacy in infertility.
AB  - OBJECTIVE: To determine whether a constant-sequence or an alternating-sequence
      design is better for the evaluation of infertility treatment efficacy when
      multiple cycles of treatment are undertaken. DESIGN: A simulation exercise using
      analytical methods. SETTING: University medical center. PATIENT(S): A
      hypothetical, heterogeneous population of infertile patients participating in a
      randomized trial comparing an experimental treatment, with effectiveness of 2.0,
      to no treatment. INTERVENTION(S): Comparison of a constant-sequence design in
      which the subject receives the same intervention or the alternating-sequence
      design in which experimental and control treatments are crossed over after each
      successive cycle. MAIN OUTCOME MEASURE(S): Relative risks of pregnancy per cycle
      and overall after a maximum of five cycles of treatment. RESULT(S): With both
      designs, the pregnancy rates in experimental and control groups showed a
      consistent decrease with each successive cycle. The overall effectiveness in the
      constant-sequence design was underestimated at 1.83, whereas in the alternating
      sequence design it was overestimated at 2.06. However, by restricting the
      analysis in the latter design only to the odd-numbered cycles, the relative risk
      was precisely correct at 2.00. CONCLUSION(S): When multiple cycles of treatment
      are undertaken to evaluate the efficacy of infertility therapy, the alternating
      sequence design with restriction of the analysis to only the odd-numbered
      treatment cycles provides an unbiased estimation of the treatment effect.

PMID- 10927052
TI  - Peritoneal fluid interleukin-6 in women with chronic pelvic pain.
AB  - OBJECTIVE: To determine the relationship between peritoneal fluid concentrations
      of interleukin-6 (IL-6) and chronic pelvic pain symptomatology in women with
      adhesions, endometriosis, or no obvious intraperitoneal pathology. DESIGN:
      Clinical research study. SETTING: Healthy volunteers in an academic research
      environment. PATIENT(S): Reproductive-aged women undergoing laparoscopy for the
      diagnosis of pelvic pain, infertility, or sterilization were selected.
      INTERVENTION(S): Peritoneal fluid was collected at the time of the laparoscopy
      and later assayed for IL-6. Subjects completed a pelvic pain questionnaire, and
      operative reports were used to obtain the underlying diagnosis. MAIN OUTCOME
      MEASURE(S): Interleukin-6 concentrations. RESULT(S): No correlation between the
      presence or absence of pelvic pain, findings of adhesions or endometriosis, and
      the concentration of peritoneal fluid IL-6 was observed. CONCLUSION(S): The
      cytokine IL-6 does not seem to play a role in the genesis of chronic pelvic pain
      in women with adhesions or endometriosis.

PMID- 10927053
TI  - Adrenocortical hyperresponsivity to adrenocorticotropic hormone: a mechanism
      favoring the normal production of cortisol in 21-hydroxylase-deficient nonclassic
      adrenal hyperplasia.
AB  - OBJECTIVE: To test the hypothesis that patients with nonclassic adrenal
      hyperplasia (NCAH) exhibit a generalized exaggeration in their response to ACTH
      stimulation that favors the normal production of F. Patients with 21-hydroxylase
      (21-OH)-deficient NCAH do not demonstrate cortisol (F) deficiency. DESIGN:
      Prospective controlled study. SETTING: Tertiary university clinic. PATIENT(S):
      Twenty-four untreated patients with NCAH diagnosed by a 17 alpha
      hydroxyprogesterone (17-HP) level of >30.3 nmol/L (>10 ng/mL), and 37 age- and
      body mass-matched healthy eumenorrheic nonhirsute controls. INTERVENTION(S): All
      study subjects underwent a 60 minute acute stimulation using 0.25 mg of ACTH-(1
      24) i.v. MAIN OUTCOME MEASURE(S): Basal and stimulated serum levels of
      pregnenolone (PREG), 17-hydroxypregnenolone (17-HPREG), dehydroepiandrosterone
      (DHA), progesterone (P4), 17-HP, androstenedione (A4), 11-deoxycortisol (S), and
      cortisol (F). RESULT(S): The median basal (i.e., Steroid(0)) or ACTH-stimulated
      (i. e., Steroid(60)) serum levels of PREG, 17-HPREG, DHA, P4, 17-HP, A4 and, most
      importantly, S were higher in NCAH patients than in controls. In contrast, the
      levels of F at either 0 minute or 60 minutes of stimulation were similar between
      NCAH and control women. The proportion of NCAH patients with stimulated steroids
      levels of >the 95th percentile of controls were as follows: 84.21% for PREG(60),
      87.5% for 17-HPREG(60), 95.8% for DHA(60), 89.5% for P4(60), 100% for 17-HP(60),
      91.7% for A4(60), 29.2% for S(60), and 4. 1% for F(60). CONCLUSION(S): A
      generalized adrenocortical hyperresponsivity to ACTH stimulation seems to be
      present in patients with 21-OH-deficient NCAH, with an exaggerated production of
      S evident in approximately 30%. The excess production of S in these NCAH patients
      may, in part, account for their normal F production.

PMID- 10927054
TI  - Do women with unexplained recurrent pregnancy loss have higher day 3 serum FSH
      and estradiol values?
AB  - OBJECTIVE: To determine the potential role of diminished ovarian reserve in
      unexplained habitual abortion. DESIGN: Retrospective comparative analysis.
      SETTING: University-based practice. PATIENT(S): Fifty-seven women who presented
      for evaluation of recurrent pregnancy loss (RPL). INTERVENTION(S): The test group
      (n = 36) comprised women with unexplained RPL. The control group (n = 21)
      comprised women with a known cause of RPL. Mean age, parity, day 3 serum FSH and
      E(2) levels, and presence or absence of a history of infertility were compared
      between groups. MAIN OUTCOME MEASURE(S): Day 3 serum FSH and E(2) levels.
      RESULT(S): Both day 3 FSH and E(2) levels were elevated in the unexplained group
      compared with the control group. When combined, FSH or E(2) levels, or both, were
      elevated in 58% of the unexplained RPL group and 19% of the control group (odds
      ratio, 5.95 [95% CI, 1.7-21.3]; P<.004). Age, parity, and presence of infertility
      did not differ between groups. CONCLUSION(S): Women with unexplained RPL have a
      greater incidence of elevated day 3 serum FSH and E(2) levels than do women with
      a known cause of RPL. Therefore, diminished ovarian reserve may contribute to
      recurrent pregnancy loss and should be considered part of the work-up for RPL.

PMID- 10927055
TI  - Histochemical localization of endometrial insulin-like growth factor binding
      protein-1 and -3 during the luteal phase in controlled ovarian hyperstimulation
      cycles: a controlled study.
AB  - OBJECTIVE: To determine if controlled ovarian hyperstimulation (COH) affects the
      endometrial expression of IGFBP-1 and IGFBP-3. DESIGN: Prospective, controlled
      study. SETTING: Tertiary infertility clinic. PATIENT(S): Eighteen oocyte donors
      undergoing COH cycles and 17 natural cycle controls. INTERVENTION(S): Controlled
      ovarian hyperstimulation, endometrial biopsies. MAIN OUTCOME MEASURE(S):
      Immunohistochemical scoring of endometrial IGFBP-1 and -3 expression,
      morphological endometrial dating, and serum estradiol (E(2)), LH, and
      progesterone (P(4)) concentrations. RESULT(S): No statistically significant
      difference was observed between natural and stimulated cycles in change in IGFBP
      1 or -3 over standardized cycle days throughout the window of embryo implantation
      (days 17-24). The IGFBP-1 and -3 expression was zero or near zero for both the
      natural and COH cycles until day 12-13. Both IGFBPs showed increased production
      throughout the secretory phase. Advanced endometrial histology (>/=1 day) in
      glands and stroma was noted in COH cycles. Significant positive correlations of
      E(2) and P(4) were noted with IGFBP-1 and -3 but not with advanced endometrial
      morphology in the COH cycles. CONCLUSION(S): The COH cycles have no significantly
      increased endometrial IGFBP-1 or -3 expression throughout the implantation phase
      of the luteal cycle compared with normal menstrual cycles. Both IGFBPs were
      absent in the proliferative phase and increased throughout the secretory portion
      of the embryo implantation window.

PMID- 10927056
TI  - Type VI collagen expression during growth of human ovarian follicles.
AB  - OBJECTIVE: To identify type VI collagen expression in human ovarian follicles
      during follicular growth. DESIGN: In vitro experiment. SETTING: Department of
      Obstetrics and Gynecology, Wakayama Medical College, Japan. PATIENT(S): Regularly
      cycling women who underwent adnexectomy. INTERVENTION(S): Immunohistochemistry
      and in situ hybridization for human type VI collagen. MAIN OUTCOME MEASURE(S):
      Expression of type VI collagen. RESULT(S): Expression of type VI collagen was
      observed in the theca cell layers during folliculogenesis, whereas no expression
      of type VI collagen was observed in the granulosa cell layers at the mRNA and
      protein levels. As the follicles grew, immunostaining for type VI collagen became
      intense in the theca cell layers, especially the theca externa. In preovulatory
      follicles, however, weak, fragmented, or discontinuous immunostaining of the
      theca cell layers was observed. This fragmented or discontinuous immunostaining
      was evident predominantly in the apical area of preovulatory follicles rather
      than in the basal area. CONCLUSION(S): Type VI collagen is present in the theca
      cell layers of follicles during folliculogenesis and plays an important role in
      interactions between the theca cells and extracellular matrix. These interactions
      may lead to changes in the shape, proliferation, migration, or differentiation of
      follicular cells during follicular development, maturation, and ovulation.

PMID- 10927057
TI  - Analysis of follicular fluid hormone concentrations and granulosa cell mRNA
      levels for the inhibin-activin-follistatin system: relation to oocyte and embryo
      characteristics.
AB  - OBJECTIVE: To explore the potential roles of inhibin, activin, and follistatin in
      human oocyte development by quantifying their intrafollicular biosynthesis.
      DESIGN: Prospective, nonrandomized study. SETTING: An IVF unit and academic
      research laboratory. PATIENT(S): Thirty one patients undergoing IVF.
      INTERVENTION(S): Human menopausal gonadotropins or human FSH (or both) were
      administered. Single-follicle aspirates (n = 110) were collected for analysis.
      MAIN OUTCOME MEASURE(S): Concentrations of dimeric, total and pro-alphaC inhibin
      forms; activin A; follistatin; estradiol; and progesterone were measured in
      follicular fluids. Granulosa-cell mRNA was analyzed for alpha, beta A, and beta B
      inhibin and activin subunits; follistatin; activin receptors; and beta-actin.
      Hormone concentrations and mRNA levels were correlated with oocytes or embryos
      from the same follicles. RESULT(S): Levels of progesterone and follistatin were
      significantly greater in follicles containing MI or MII oocytes than in those
      containing GV oocytes. Inhibin alpha-subunit mRNA levels were significantly
      higher in follicles containing maturing oocytes, the highest-quality oocytes, and
      oocytes that were subsequently fertilized. In contrast, inhibin alpha-subunit
      mRNA levels were significantly lower in follicles from which higher-quality
      embryos were obtained. CONCLUSION(S): Inhibin alpha-subunit biosynthesis is
      associated with normal oocyte and follicle maturation, but excessive alpha
      inhibin is associated with poor embryo quality. None of the hormones analyzed
      were associated with oocyte or embryo quality.

PMID- 10927058
TI  - Effect of particle size on the prolonged action of subcutaneous danazol in male
      and female rats.
AB  - OBJECTIVE: To investigate the effects of two different particle sizes of danazol
      in male and female rats. DESIGN: Prospective, vehicle-controlled study. SETTING:
      Undergraduate college research facility and medical research laboratory. ANIMALS:
      18 castrated male rats and 18 cycling female rats. INTERVENTION(S): Preparations
      of danazol with particle sizes of 2.05 microm or 5.2 microm were administered as
      a single subcutaneous injection of 400 mg/kg to castrated male rats or estrus
      cycling females. MAIN OUTCOME MEASURE(S): Serum LH level in males and estrous
      cycle length in females. RESULT(S): In males, both preparations significantly
      (P<. 001) suppressed serum LH by day 5 of treatment. Gonadotropin levels remained
      low throughout the 35-day study in rats that received the larger-particle
      danazol, whereas LH levels began to increase after 25 days in rats that received
      smaller-particle danazol. In females, the normal 4- to 5-day estrous cycle
      interval was prolonged to 38.7 days (P<.001) in those that received the larger
      particle danazol and 25.5 days in those that received the smaller-particle
      danazol. CONCLUSION(S): The results demonstrate the prolonged effectiveness of a
      single subcutaneous dose of danazol and indicate that one might be able to
      predict the effective duration of activity by changing the particle size of the
      danazol administered.

PMID- 10927059
TI  - Depletion of Raf-1 protooncogene by geldanamycin causes apoptosis in human
      luteinized granulosa cells.
AB  - OBJECTIVE: To investigate the hypothesis that epidermal growth factor (EGF)
      signaling in luteinized granulosa cells works through Raf-1 and mitogen-activated
      protein (MAP) kinases and that depletion of Raf-1 by geldanamycin will inhibit
      the signaling pathway and cause apoptosis. DESIGN: Laboratory study. SETTING:
      University of Minnesota. PATIENT(S): Human luteinized granulosa cells from IVF
      patients. INTERVENTION(S): The cells were treated with vehicle (DMSO), 0.5 microM
      of geldanamycin, 10 ng/mL of EGF, and geldanamycin + EGF. MAIN OUTCOME
      MEASURE(S): Radiochemical MAP kinase assay, Western blotting, confocal
      microscopy, and flow cytometry. RESULT(S): Geldanamycin treatment depleted Raf-1
      and lowered MAP kinase activity in luteinized granulosa cells. EGF treatment
      increased MAP kinase phosphorylation and translocation of the phosphorylated MAP
      kinase to the nucleus. Geldanamycin blocked this effect. Cleavage of caspase-3,
      the executioner protein in apoptosis, into an active 17 kD fragment was observed
      by Western blotting in geldanamycin-treated cells. Finally, by flow cytometry we
      observed significantly increased percentages of subdiploid apoptotic nuclei in
      geldanamycin-treated cells. CONCLUSION(S): In human luteinized granulosa cells,
      EGF works through Raf-1, and MAP kinase and depletion of Raf-1 by geldanamycin
      resulted in decreased MAP kinase activity, increased activated caspase-3, and,
      ultimately, apoptosis.

PMID- 10927060
TI  - Follicular development in transplanted fetal and neonatal mouse ovaries is
      influenced by the gonadal status of the adult recipient.
AB  - OBJECTIVE(S): To investigate the pattern of follicular development in
      transplanted fetal and neonatal mouse ovaries in the presence or absence of the
      recipient's own ovaries. DESIGN: Controlled experiment. SETTING: Academic
      research laboratory, Department of Physiology, Monash University, Clayton,
      Australia. INTERVENTION(S): Mouse ovaries from 16-day-old fetuses, 3-day-old
      neonates, and 10-day-old neonates were transplanted under the kidney capsule of
      adult female mice, which either retained their own ovaries in situ or were
      bilaterally ovariectomized. MAIN OUTCOME MEASURE(S): Histologic analysis.
      RESULT(S): By 4 weeks after transplantation, fetal and neonatal ovaries
      transplanted to ovariectomized recipients displayed a pattern of follicular
      development similar to that observed in in situ adult mouse ovaries. In contrast,
      follicular development did not progress beyond the early antral stage in fetal
      and 3-day-old ovaries transplanted to recipients that retained their in situ
      ovaries. However, 10-day-old ovaries transplanted to recipients that retained
      their in situ ovaries displayed full follicular development and corpora lutea
      formation by 8 weeks after transplantation. CONCLUSION(S): Follicular development
      in transplanted immature ovarian tissue is influenced by the age of the donor
      ovary and gonadal status of the recipient. (Fertil Steril(R) 2000;74:000-00.
      Copyright2000 by American Society for Reproductive Medicine.)

PMID- 10927061
TI  - Modified hysterosalpingography during infertility work-up: use of contrast medium
      and saline to investigate mechanical factors.
AB  - OBJECTIVE: To evaluate the effectiveness of modified hysterosalpingography using
      <3 mL amount of contrast medium followed by injection of saline to minimize the
      adverse effects associated with the procedure. DESIGN: For modified
      hysterosalpingography, 1-2 mL of water-soluble contrast medium were injected to
      visualize the uterine cavity, followed by injection of 10 mL of saline to check
      tubal patency and spillage. A control group of patients underwent
      hysterosalpingography with undiluted contrast medium. SETTING: Teaching hospital.
      PATIENT(S): Seventy-eight infertile women [study (n = 40)/control (n = 38)
      groups]. INTERVENTION(S): Modified and standard hysterosalpingography. MAIN
      OUTCOME MEASURE(S): Assessment of uterine cavity, tubal patency, and sensation of
      pain during modified hysterosalpingography was compared with that during standard
      hysterosalpingography. RESULT(S): Uterine cavity and tubal patency were properly
      visualized during modified hysterosalpingography. Saline pushed the contrast
      medium successfully from the uterine cavity through the open fallopian tubes and
      into the pelvic cavity. The study group reported significantly less pain than did
      the control group. Between-group differences were statistically significant when
      pain perception (no pain vs. minimal pain vs. severe pain; no pain vs. any kind
      of pain) was analyzed by type of adnexal pathology (bilateral passage or
      unilateral passage). CONCLUSION(S): Modified hysterosalpingography was sufficient
      to diagnose tubal and pelvic mechanical factors. The procedure was associated
      with a significant reduction in self-reported pain and no medical complications.

PMID- 10927063
TI  - Testicular sperm extraction by Trucut needle and milking of seminiferous tubules:
      a technique with high yield and patient acceptability.
AB  - OBJECTIVE: To assess the sperm yield and patient acceptability of Trucut needle
      testicular biopsy followed by seminiferous tubule milking. DESIGN: Prospective
      case analysis. SETTING: The Regional Fertility Center, Royal Maternity Hospital,
      Belfast, Northern Ireland, United Kingdom. PATIENT(S): Forty-one males with
      obstructive azoospermia (normal testicular volume and FSH and LH levels).
      INTERVENTION(S): Trucut needle testicular biopsies under local anesthetic with
      milking of the seminiferous tubules. MAIN OUTCOME MEASURE(S): Quantitation of
      sperm retrieved per biopsy core and patient follow-up by questionnaire.
      RESULT(S): A mean of 105,634 sperm (range, 5,000-427,800) were retrieved, and the
      mean biopsy weight was 9.17 mg. Twenty-six subjects found the biopsy painless and
      15 were pain-free after biopsy. CONCLUSION(S): The Trucut needle can be used in
      combination with seminiferous tubule milking to obtain large numbers of sperm in
      men with obstructive azoospermia.

PMID- 10927062
TI  - Minilaparoscopic ovarian drilling under local anesthesia in patients with
      polycystic ovary syndrome.
AB  - OBJECTIVE: To assess pain control in patients with polycystic ovary syndrome
      (PCOS) who are undergoing ovarian drilling during minilaparoscopy under local
      anesthesia and conscious sedation and to evaluate the efficacy of this protocol
      compared with the traditional approach in terms of operative and discharge times,
      subsequent ovulation, and pregnancy. DESIGN: Prospective randomized study.
      SETTING: University hospitals and private day-surgery unit. PATIENT(S): Sixty-two
      infertile women with PCOS. INTERVENTION(S): Group A underwent minilaparoscopic
      ovarian drilling under local anesthesia and conscious sedation. Group B (control
      group) was treated with traditional ovarian drilling by laparoscopy under general
      anesthesia. MAIN OUTCOME MEASURE(S): Intraoperative pain score in group A.
      Hormonal profile before and after surgery, operative and discharge times,
      postoperative analgesic requirements, and reproductive follow-up in both groups.
      RESULT(S): Group A showed a good intraoperative pain score. The hormonal profile
      after surgery did not differ between groups A and B. Operative times were also
      similar for both groups. The number of patients discharged within 2 hours after
      surgery was significantly higher in group A. The need for postoperative
      analgesics was significantly higher in group B. No statistically significant
      differences were noted between the groups in terms of pregnancy and ovulation
      rates. CONCLUSION(S): Intraoperative and postoperative local anesthesia plus
      conscious sedation allows outpatient bilateral ovarian drilling by
      minilaparoscopy to be performed without general anesthesia. The high pregnancy
      rates, the simplicity of the method, and the faster discharge time offer a new
      option for patients with PCOS who are resistant to clomiphene citrate. Moreover,
      ovarian cauterization can be performed simultaneously with a diagnostic
      minilaparoscopy and integrated into the infertility workup of these patients.

PMID- 10927064
TI  - Laparoscopic creation of a neovagina in patients with Rokitansky syndrome:
      analysis of 52 cases.
AB  - OBJECTIVE: To evaluate the surgical feasibility and the long-term anatomic and
      functional results of a new procedure that uses the endoscopic approach to treat
      uterovaginal agenesis, known as Rokintansky syndrome. DESIGN: Evaluation of
      surgical feasibility and recording of clinical data over a 12-month follow-up.
      SETTING: Tertiary referral center for the treatment of female genital
      malformations. PATIENT(S): Fifty-two patients with vaginal agenesis.
      INTERVENTION(S): The laparoscopic version of the Vecchietti method was used to
      create a neovagina. MAIN OUTCOME MEASURE(S): Anatomic success was defined as a
      neovagina >/=6 cm long, allowing easy introduction of two fingers, within 6
      months after corrective surgery. Functional success was considered achieved if
      the patient reported satisfactory sexual intercourse starting from 6 months after
      surgery. RESULT(S): The surgical procedure was performed with no major
      complications and with 100% anatomic success; functional success was obtained in
      98.1% of the study population. CONCLUSION(S): In patients with Rokitansky
      syndrome, the laparoscopic approach for creating a neovagina by the Vecchietti
      method is simple, safe, and effective.

PMID- 10927065
TI  - Zygote intrafallopian transfer in patients with tubal factor infertility after
      repeated failure of implantation with in vitro fertilization-embryo transfer.
AB  - OBJECTIVE: To evaluate the efficacy of zygote intrafallopian transfer (ZIFT) in
      terms of implantation and pregnancy rates in patients with tubal factor
      infertility and repeated implantation failure in IVF-ET cycles. DESIGN:
      Retrospective analysis of ZIFT cycles. SETTING: An IVF unit in a university
      hospital. PATIENT(S): Criteria for patient selection for ZIFT included at least
      four failures of implantation in IVF-ET cycles in which at least 3 embryos were
      replaced per transfer and a cause of infertility diagnosed as male, unexplained,
      or tubal factor with proof of one patient tube. INTERVENTION(S): Four to six
      zygotes were transferred by laparoscopy into the fallopian tube 24-26 hours after
      oocyte retrieval. MAIN OUTCOME MEASURE(S): Implantation and pregnancy rates were
      determined in 112 ZIFT cycles performed in 81 patients with repeated failure of
      implantation. Results were further stratified for patients with tubal factor (n =
      15) and patients without tubal factor (n = 66). RESULT(S): The pregnancy and
      implantation rates for all ZIFT cycles were 35.1% and 11.1%, respectively.
      Pregnancy and implantation rates per cycle in patients with tubal factor versus
      patients without tubal factor were 26.6% versus 37.1% and 9.4% versus 11.4%,
      respectively. CONCLUSION(S): ZIFT can be considered as a mode of treatment for
      patients with repeated failure of implantation in IVF-ET and with tubal factor
      with proved patency of one tube.

PMID- 10927066
TI  - Polycystic ovary syndrome, infertility, familial thrombophilia, familial
      hypofibrinolysis, recurrent loss of in vitro fertilized embryos, and miscarriage.
AB  - OBJECTIVE: To study reversible determinants of infertility and recurrent loss of
      transferred embryos after failure of 7 of 10 embryo transfers, 1 live birth, and
      2 miscarriages. DESIGN: Measures of thrombophilia, hypofibrinolysis, reproductive
      hormones, and androgenic steroids before and after metformin therapy. SETTING:
      Outpatient clinical research center. PATIENT(S): A 32-year-old amenorrheic,
      infertile woman with polycystic ovary syndrome (PCOS) who had 7 of 10 embryo
      transfers fail, 1 premature live birth, and 2 miscarriages at 8 and 17 weeks.
      INTERVENTION(S): Metformin (2.55 g/d) was given to ameliorate the endocrinopathy
      of PCOS. MAIN OUTCOME MEASURE(S): Coagulation, insulin, reproductive hormones,
      and androgenic steroids. RESULT(S): The propositus had thrombophilia (familial
      protein S deficiency [free protein S 32%; normal >/=65%]). She also had familial
      hypofibrinolysis with 4G4G polymorphism of the plasminogen activator inhibitor
      (PAI-1) gene and high PAI-1 activity (PAI-Fx), 42.5 U/mL, normal <21.1.
      Polycystic ovary syndrome was characterized by amenorrhea, polycystic ovaries,
      high fasting serum insulin (39 microU/mL, normal <20), androstenedione (763
      ng/dL, normal <250), and testosterone (229 ng/dL, normal <83). After she received
      metformin for 4 months, PAI-Fx normalized (12.4 U/mL), as did insulin (12
      microU/mL), androstenedione (185 ng/dL), and testosterone (39 ng/dL); weight fell
      from 109 to 91.3 kg (16%). CONCLUSION(S): Metformin reversed the endocrinopathy
      of PCOS. Familial thrombophilia and hypofibrinolysis may lead to thrombosis
      mediated uteroplacental vascular insufficiency, failure to achieve pregnancy
      after embryo transfer, and miscarriage.

PMID- 10927067
TI  - Infertility is a symptom, not a disease.

PMID- 10927068
TI  - Absence of Y-chromosome microdeletions in patients with isolated hypospadias.

PMID- 10927069
TI  - The low responder female IVF patient with hypogonadotropic hypogonadism: do not
      give up!

PMID- 10927070
TI  - A case of spontaneous ovarian hyperstimulation syndrome with a potential mutation
      in the hCG/LH receptor gene.

PMID- 10927071
TI  - Massive retroperitoneal bleeding: a complication of transvaginal ultrasonography
      guided oocyte retrieval for in vitro fertilization-embryo transfer.

PMID- 10927072
TI  - Laparoscopic cornual excision in a viable large interstitial pregnancy without
      blood flow detected by color Doppler ultrasonography.

PMID- 10927073
TI  - A full-term pregnancy in a patient with a severe mullerian duct anomaly with
      obstruction.

PMID- 10927074
TI  - Novel conservative medical therapy for uterine adenomyosis with a danazol-loaded
      intrauterine device.

PMID- 10927075
TI  - Lack of effect of topical finasteride suggests an endocrine role for
      dihydrotestosterone.

PMID- 10927076
TI  - Retrograde ejaculation: can sperm retrieval be simpler and noninvasive?

PMID- 10927077
TI  - A novel method (FotoMaster) of documenting endoscopic surgical procedures.

PMID- 10927078
TI  - The challenge of meta-analysis and the need to register clinical trials.

PMID- 10927079
TI  - The challenge of meta-analysis and the need to register clinical trials.

PMID- 10927081
TI  - A European perspective on Neospora caninum.
AB  - Since the identification of Neospora caninum in 1984 as a parasite separate from
      Toxoplasma gondii by Bjerkas et al., and its subsequent characterization and
      classification in 1988 by Dubey and co-workers, this parasite has attracted
      increasing attention, primarily as an important causative agent of abortion in
      cattle and neuromuscular disease in dogs, but also as a complementary model
      system to T. gondii for investigating the basic biology of intracellular
      parasitism. During November 11-14, 1999, the COST 820 Annual meeting (Vaccines
      against coccidioses) took place in Interlaken, Switzerland. Almost half of the
      papers presented at that meeting were on N. caninum and neosporosis, reflecting
      the increasing awareness of the importance of this parasite on part of the
      scientific community in Europe. On the occasion of the meeting, participants in
      this COST Action involved in Neospora research in Europe were asked to
      participate in this invited review in order to document the growing interest in
      N. caninum and the disease it causes. Thus, this paper is a unique collection of
      contributions provided by several European experts in the field. It is comprised
      of 10 reviews or original papers on different aspects of Neospora research
      including epidemiology, immunology, application and development of serological
      tools, and molecular characterisation of the parasite currently carried out
      throughout Europe. In addition, two distinguished invited speakers from overseas
      (Milton McAllister and John Ellis) provided valuable contributions. This invited
      review demonstrates that the COST 820 Action has brought together scientists from
      all over Europe and other parts of the world, and has laid the basis for many
      fruitful collaborations. The studies described here will contribute in assessing
      the relevance of neosporosis as a potential risk factor not only for animals, but
      also for human health.

PMID- 10927082
TI  - Characterisation of proteases involved in egg hatching of the sheep blowfly,
      Lucilia cuprina.
AB  - A number of proteases were identified in the egg shell washings (ESW) collected
      during the egg hatching of Lucilia cuprina (sheep blowfly). Characterization of
      these proteases indicated a pH optima in a similar pH range that was optimal for
      L. cuprina egg hatching. Mechanistic characterization of these proteases
      indicated that they were predominantly of the serine class. Several protease
      inhibitors were tested for their ability to inhibit L. cuprina egg hatching in
      vitro. Egg hatching was significantly (P<0.05) inhibited by PMSF (61%), 1,10
      Phenanthroline (42%) and Pepstatin (29%). The inhibition of egg hatching by PMSF
      showed a strong concentration dependence, with its effects ranging from
      inhibition at high concentrations to enhancement of egg hatching at low
      concentrations. Addition of ESW to unhatched eggs, significantly (P<0.05)
      enhanced their rate of hatching above untreated control eggs. This enhancement of
      egg hatching was significantly (P<0.05) reversed by the protease inhibitors
      Elastatinal (40%), 1,10-Phenanthroline (40%) and PMSF (38%). These studies
      indicate a role for serine and/or metallo-proteases in facilitating L. cuprina
      egg hatch.

PMID- 10927083
TI  - Mitochondrial DNA polymorphism within and among species of Capillaria sensu lato
      from Australian marsupials and rodents.
AB  - The nucleotide variation in a mitochondrial DNA (mtDNA) fragment within and among
      species of Capillaria sensu lato from Australian marsupials and rodents was
      analyzed using a mutation scanning/sequencing approach. The fragment of the
      cytochrome c oxidase subunit I (COI) was amplified by PCR from parasite DNA, and
      analysed by single-strand conformation polymorphism (SSCP) and sequencing. There
      was no significant variation in SSCP profiles within a morphospecies from a
      particular host species, but significant variation existed among morphospecies
      originating from different host species. The same morphospecies was found to
      occur in 1-3 tissue habitats within one host individual or within different
      individuals of a particular species of host from the same or different
      geographical areas, and morphospecies appeared to be relatively host specific at
      the generic level. The results indicated that the species of Capillaria sensu
      lato examined, although highly variable in their host and tissue specificity, may
      exhibit the greatest degree of specificity at the level of host genus.

PMID- 10927084
TI  - The small subunit ribosomal RNA sequence of Strongyloides stercoralis.
AB  - The published small subunit rRNA (ssrRNA) gene sequences for Strongyloides ratti
      and Strongyloides stercoralis are remarkably divergent, particularly in the 5'
      400 bases of the approximately 1700 base pair (bp) sequences. This level of
      divergence between species nominally in the same genus was unprecedented. We have
      redetermined the ssrRNA sequence of S. stercoralis and find that the published
      sequence is a chimaera of parasite and fungal segments. The true sequence for S.
      stercoralis ssrRNA is very similar to that of S. ratti.

PMID- 10927085
TI  - Molecular characterisation of the Theileria buffeli/orientalis group.
AB  - Benign bovine Theileria parasites known as either Theileria buffeli, Theileria
      orientalis or Theileria sergenti are classified on basis of their morphology,
      vector specificity, pathogenicity and 18S small subunit ribosomal RNA or major
      piroplasm protein (MPSP) sequences. Since most isolates have been characterized
      on only some of these criteria and the existing confusion in nomenclature, an
      analysis was performed on eight different isolates to combine 18S rRNA data with
      MPSP data and the results were compared with available biological parameters. A
      polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)
      approach for both genes was used in combination with reverse line blot
      hybridisation for the 18S rRNA gene. Both MPSP and 18S rRNA genes were cloned and
      sequenced from parasites displaying aberrant MPSP RFLP profiles. Phylogeny based
      on published and determined 18S rRNA and MPSP sequences did correlate within the
      same isolate but there was no obvious correlation between molecular and
      biological data. Based on these findings, we suggest that the appropriate name
      for all these parasites is Theileria buffeli. A more specific nomenclature should
      be assigned when new molecular markers may become available.

PMID- 10927086
TI  - Comparison of hepatic and renal drug-metabolising enzyme activities in sheep
      given single or two-fold challenge infections with Fasciola hepatica.
AB  - The activity of drug-metabolising enzymes was compared in liver and kidneys of
      adult sheep given single or two-fold fluke infection. Fascioliasis was induced by
      oral administration of 200 metacercariae of Fasciola hepatica to female sheep
      either 10 or 20 weeks (mono-infections) or 10 and 20 weeks (bi-infection) before
      killing. The parasitic pathology was ascertained at autopsy and by clinical
      observation of animals. In the liver of both mono- and bi-infected animals,
      significant decreases (P<0.05) (17-44%) were observed in the microsomal content
      of cytochrome P450 and in the two measured P450-dependent monooxygenase
      activities, benzphetamine and ethylmorphine N-demethylations. Moreover, Western
      blot analysis of microsomes demonstrated a decrease in the expression of
      cytochrome P4503A subfamily correlative with that of its presumed corresponding
      activity ethylmorphine N-demethylase. By contrast, the conjugation of chloro
      dinitrobenzene to glutathione remained unchanged in liver cytosolic fractions
      prepared from all these animals. In kidneys, a significant decrease (P<0.05)
      (30%) in microsomal cytochrome P450 level of 10-week mono-infected sheep was
      observed whereas there was no change in the other groups of animals. The
      inflammatory origin and the consequences in terms of pathology and animal
      productivity of the fascioliasis-induced decreases in tissue-oxidative drug
      metabolism are discussed, particularly in the case of adult sheep suffering
      repetitive infections.

PMID- 10927087
TI  - Efficacy of Droncit Spot-on (praziquantel) 4% w/v against immature and mature
      Echinococcus multilocularis in cats.
AB  - The causative agent of alveolar hydatidosis in humans, the fox tapeworm
      Echinococcus multilocularis, is extending its geographical range in Europe and
      has been found in domestic cats in some areas. A dermally applied cestocidal
      treatment for domestic cats has been developed and the efficacy of this treatment
      is reported. Thirty purpose-bred cats were experimentally infected each with
      10000 protoscoleces of Echinococcus multilocularis. Ten days later one group of
      ten cats was treated with Droncit(R) Spot-on (Praziquantel) 4% w/v dermally in
      one place on the dorsal aspect of the neck at a dose of 8 mg/kg. Eleven days
      later (21 days p.i.) a second group of ten cats was also treated with Droncit(R)
      Spot-on the same way. One group of ten cats was left untreated as controls.
      Twenty three days after infection the cats were examined for the presence of E.
      multilocularis tapeworms. No E. multilocularis were recovered from any of the
      cats in either of the treated groups. Echinococcus multilocularis were recovered
      from eight of the ten cats left untreated as controls. The worm burdens in the
      untreated cats were 0, 0, 5, 15, 75, 110, 220, 815, 2635, and 3045 worms per cat.
      The worms ranged in development from the three to four segment stage. Many of the
      E. multilocularis with four segments contained unshelled eggs in the terminal
      segment. This study indicates that Droncit(R) Spot-on (Praziquantel) 4% w/v
      applied dermally at 8 mg/kg is highly effective in removing E. multilocularis
      from the small intestine of cats infected with immature and mature (prepatent)
      infections of E. multilocularis. In the cats with the mature infections all
      tapeworms were absent from the small intestine within 2 days of treatment.

PMID- 10927110
TI  - Why we need reading-glasses before a zimmer-frame.
AB  - Accommodative loss represents the fastest human biological decrement. Why? To
      examine this, the shape of the eye-lens during accommodation or its relaxation is
      analysed with special reference to age-related changes. The capsule is viewed as
      a force transmitter: the distribution of forces along centripetal capsular arcs
      and the resulting stresses and strains are calculated. The effect of zonular
      'shifts' is considered. Age-related accommodative loss can be modelled
      successfully if changes in mechanical properties are linked to those in
      lenticular and capsular shape.

PMID- 10927111
TI  - Visual pigment reconstitution in intact goldfish retina using synthetic
      retinaldehyde isomers.
AB  - A protocol has been developed for reconstituting visual pigments in intact
      retinae by delivering synthetic isomers of retinal incorporated in phospholipid
      vesicles. Calibration curves have been constructed relating the lambda(max) of
      the native porphyropsins (visual pigments based on 11-cis 3-dehydroretinal) of
      the rods and four spectral classes of cone in the goldfish, and the equivalent
      photosensitive pigments regenerated from 11-cis retinal (rhodopsins) and the
      commercially available isomer, 9-cis retinal (isorhodopsins). The relationship
      between the lambda(max) of rhodopsins and isorhodopsins appears to be linear,
      such that the difference in lambda(max) changes sign at about 380 nm. We
      therefore conclude that the protocol for reconstituting visual pigments with 9
      cis retinal is suitable for all classes of vertebrate opsin-based photopigments.

PMID- 10927112
TI  - Modulation of constant light effects on the eye by ciliary ganglionectomy and
      optic nerve section.
AB  - Our previous studies have shown that an environment of constant light (CL) can
      lead to development of high degree of hyperopia in newborn chicks by inducing
      severe corneal flattening, and compensatory growth of the vitreous chamber. We
      wish to know whether the abnormal eye growth and progressive hyperopia under CL
      conditions is accomplished by a mechanism that uses the visual processing
      pathways of the central nervous system (CNS) or by a mechanism located in the
      eye. Thirty white leghorn chicks (Cornell K-strain) were raised under 12 h
      light/12 h dark (12L/12D) for either optic nerve section (ONS) or ciliary
      ganglion section (CGS). Another 30 chicks were raised under CL for ONS or CGS.
      Refractive states and corneal curvatures were measured by infrared (IR)
      photoretinoscopy and IR keratometry, respectively. The axial lengths of the
      ocular components were measured by A-scan ultrasonography. Both ONS and CGS
      surgery produced dilated pupils and accommodative paralysis. Four weeks after
      surgery, CGS eyes exhibited a hyperopic defocus, flatter cornea, and shorter
      vitreous chamber depth under both CL and normal conditions, whereas ONS eyes
      showed a smaller radius of corneal curvature and shallow vitreous chamber only in
      the normal light cycle group. CGS eyes of CL chicks showed significantly deeper
      vitreous chambers than did fellow control eyes. Our results indicate that optic
      nerve section does not seem to influence CL effects. Thus, local mechanisms may
      play a major role in the ocular development of chicks. The ciliary nerve is
      necessary for the normal corneal and anterior chamber growth, and prevents CL
      effects. The progressively increasing vitreous chamber depth under CL may be
      influenced by both local and central mechanisms.

PMID- 10927113
TI  - Phi is not beta, and why Wertheimer's discovery launched the Gestalt revolution.
AB  - Max Wertheimer (1880-1943), the founder of the Gestalt School of Psychology,
      published a monograph on the perception of apparent motion in 1912, which
      initiated a new direction for a great deal of subsequent perceptual theory and
      research. Wertheimer's research was inspired by a serendipitous observation of a
      pure apparent movement, which he called the phi-phenomenon to distinguish it from
      optimal apparent movement (beta), which resembles real movement. Wertheimer
      called his novel observation 'pure' because it was perceived in the absence of
      any object being seen to change its position in space. The phi-phenomenon, as
      well as the best conditions for seeing it, were not described clearly in this
      monograph, leading to considerable subsequent confusion about its appearance and
      occurrence. We review the history leading to the discovery of the phi-phenomenon,
      and then describe: (i) a likely source for the confusion evident in most
      contemporary research on the phi-phenomenon; (ii) the best conditions for seeing
      the phi-phenomenon; (iii) new conditions that provide a particularly vivid phi
      phenomenon; and (iv) two lines of thought that may provide explanations of the
      phi-phenomenon and also distinguish phi from beta.

PMID- 10927114
TI  - Neither occlusion constraint nor binocular disparity accounts for the perceived
      depth in the 'sieve effect'.
AB  - Current notions of binocular depth perception include (1) neural computations
      that solve the correspondence problem and calculate retinal positional disparity,
      and (2) recovery of ecologically valid occlusion relationships. The former
      framework works well for stimuli with unambiguous interocular correspondence, but
      less so for stimuli without well-defined disparity cues. The latter framework has
      been proposed to account for the phenomenon of perceived depth in stimuli without
      interocular correspondence, but its mechanism remains unclear. In order to obtain
      more insight into the mechanism, we studied the depth percept elicited by a
      family of stereograms - 'sieve' stimuli, adapted from Howard (1995) [Perception,
      24, 67-74] - with interocular differences but no well-defined positional
      disparity cue. The perceived depth was measured by comparison to references at
      various depths established by standard retinal disparity and was consistently
      found to lie behind the fixation plane. Moreover, the magnitude of the depth
      percept depended on both the horizontal and vertical spatial characteristics of
      the stimulus in ways that were at odds with constraints of occlusion geometry. In
      comparison to the depth percept elicited by stimuli with well-defined disparity
      cues, the precision of the percept from the sieve stimuli was 10-20 times worse,
      suggesting that a different underlying computation was involved. Thus, neither of
      the above frameworks accounts for the depth percept arising from these stimuli.
      We discuss implications of our results for physiologically based computations
      underlying binocular depth perception.

PMID- 10927115
TI  - Exploring the dynamics of light adaptation: the effects of varying the flickering
      background's duration in the probed-sinewave paradigm.
AB  - In the probed-sinewave paradigm, threshold for detecting a probe is measured at
      various phases with respect to a sinusoidally-flickering background. Here we vary
      the duration of the flickering background before (and after) the test probe is
      presented. The adaptation is rapid; after approximately 10-30 ms of the
      flickering background, probe threshold is the same as that on a continually
      flickering background. It is interesting that this result holds at both low (1. 2
      Hz) and middle (9.4 Hz) frequencies because at middle frequencies (but not at
      low) there is a dc-shift, i.e. probe threshold is elevated at all phases relative
      to that on a steady background (of the same mean luminance). We compare our
      results to predictions from Wilson's model [Wilson (1997), Visual Neuroscience,
      14, 403-423; Hood & Graham (1998), Visual Neuroscience, 15, 957-967] of light
      adaptation. The model predicts the rapid adaptation, and the dc-shift, but not
      the detailed shape of the probe-threshold-versus-phase curve at middle
      frequencies.

PMID- 10927116
TI  - Coincidence detectors: visual processing of a pair of lines and implications for
      shape discrimination.
AB  - The psychophysical data reported here bear on how the boundaries of an object's
      retinal image are processed in early vision. We propose that the visual system
      contains a mechanism sensitive to four relationships between two local stimuli
      some distance apart and that the output of this hypothetical mechanism encodes
      and labels orthogonally the four relationships. We measured the just-noticeable
      difference in the orientation difference between two test lines as well as the
      just-noticeable differences in their mean orientation, mean location, and
      separation. A pair of noise lines was located between the two test lines. By
      arranging that trial-to-trial variations in the orientation difference, mean
      orientation, mean location and separation of the test lines had zero correlation
      with each other and with trial-to-trial variations in the corresponding variables
      for the two noise lines we could demonstrate that psychophysical responses were
      based on the task-relevant variable and that, for each of the four task-relevant
      variables, all task-irrelevant variables were ignored. The finding that responses
      to the test lines were unaffected by the noise lines implies that discriminations
      were not influenced by first-stage spatial filters with strictly local receptive
      fields that responded to both test lines. Because these findings held for a
      presentation duration of 20 ms we can exclude the possibility that observers
      compared the two test lines by shifting either fixation or attention. We propose
      that, rather than by attending to two different locations, the test lines were
      selected by attending to the output of the long-distance comparator whose
      'separation' label signaled the largest magnitude. The above proposals can
      account for several previously reported phenomena. More generally, an array of
      the proposed long-distance comparators constitutes a system that may be capable
      of specifying the shape, size, location and implicit orientation of an object's
      retinal image.

PMID- 10927117
TI  - Detecting disorder in spatial vision.
AB  - In normal foveal vision, visual space is accurately mapped from retina to cortex.
      However, the normal periphery, and the central field of strabismic amblyopes have
      elevated position discrimination thresholds, which have often been ascribed to
      increased 'intrinsic' spatial disorder. In the present study we evaluated the
      sensitivity of the human visual system (both normal and amblyopic) to spatial
      disorder, and asked whether there is increased 'intrinsic' topographical disorder
      in the amblyopic visual system. Specifically, we measured thresholds for
      detecting disorder (two-dimensional Gaussian position perturbations) either in a
      horizontal string of N equally spaced samples (Gabor patches), or in a ring of
      equally spaced samples over a wide range of feature separations. We also
      estimated both the 'equivalent intrinsic spatial disorder' and sampling
      efficiency using an equivalent noise approach. Our results suggest that both
      thresholds for detecting disorder, and equivalent intrinsic disorder depend
      strongly on separation, and are modestly increased in strabismic amblyopes.
      Strabismic amblyopes also show markedly reduced sampling efficiency. However,
      neither amblyopic nor peripheral vision performs like ideal or human observers
      with added separation-independent positional noise. Rather, the strong separation
      dependence suggests that the 'equivalent intrinsic disorder' may not reflect
      topographic disorder at all, but rather may reflect an abnormality in the
      amblyopes' Weber relationship.

PMID- 10927118
TI  - Seeing circles: what limits shape perception?
AB  - Humans are remarkably adept at judging shapes and discriminating forms. Forms and
      shapes are initially sampled by discrete localized visual filters (or receptive
      fields) in 'early' stages of visual processing. However, more complex higher
      level filters which integrate or pool information from many local filters may be
      needed to discern shapes. In order to understand the mechanisms that limit shape
      perception we asked observers to detect distortions in the shape of briefly
      presented circles constructed out of samples (Gabor patches, which are well
      matched to the early visual filters), and varied the radius of the circle, and
      the number and orientation of the samples. Our results show that shape perception
      is determined by two factors: the primary determinant is the separation between
      the samples; however, the orientation of the samples can modulate performance. At
      small separations, performance is best when the samples are aligned with the
      global shape, poorer when they are orthogonal, and intermediate when they are all
      horizontal or vertical. At larger separations these contextual differences
      disappear; however at all separations, performance is reduced when the
      orientations of the samples are mixed (i.e. each sample is randomly either
      aligned or orthogonal, or randomly either horizontal or vertical.). These results
      suggest an important role for sample separation in shape perception for sampled
      shapes and suggest that the mechanisms involved in feature binding may modulate
      the responses of the mechanisms underlying shape perception.

PMID- 10927119
TI  - The use of an implicit standard for measuring discrimination thresholds.
AB  - We measured thresholds for comparing the separation between lines, using either
      the method of constant stimuli (MCS) or the method of single stimuli (MSS). In
      the MCS an explicit standard is presented on each trial, whereas in the MSS the
      standard is the mean of the set. The thresholds for the MSS procedure were nearly
      identical to those with the MCS procedure, whether or not feedback was used. A
      statistical model is presented showing how the threshold error estimated by MSS
      varies according to the number of past stimuli used by the observer to calculate
      the mean of the set. If the model is an accurate representation of human
      processing, our observers were averaging over the last 10-20 trials to estimate
      the implicit standard. Our results show that the explicit standard in the MCS
      procedure is generally superfluous. Provided that the test range is small, and
      that the observer is given some practice trials, thresholds measured with MSS
      procedure are just as precise as those measured with the traditional MCS
      procedure.

PMID- 10927120
TI  - Location cue validity affects inhibition of return of visual processing.
AB  - Inhibition-of-return is the process by which visual search for an object
      positioned among others is biased toward novel rather than previously inspected
      items. It is thought to occur automatically and to increase search efficiency. We
      examined this phenomenon by studying the facilitative and inhibitory effects of
      location cueing on target-detection response times in a search task. The results
      indicated that facilitation was a reflexive consequence of cueing whereas
      inhibition appeared to depend on cue informativeness. More specifically, the
      inhibition-of-return effect occurred only when the cue provided no information
      about the impending target's location. We suggest that the results are consistent
      with the notion of two levels of visual processing. The first involves rapid and
      reflexive operations that underlie the facilitative effects of location cueing on
      target detection. The second involves a rapid but goal-driven inhibition
      procedure that the perceiver can invoke if doing so will enhance visual search
      performance.

PMID- 10927121
TI  - Effect of visual background on saccade adaptation in monkeys.
AB  - The brain maintains saccade accuracy by modifying saccades that are consistently
      inaccurate (e.g. hypermetric). To determine whether this adaptation is influenced
      by the visual background we used several different target and background
      movements to elicit changes in saccade gain. In almost all cases, the target spot
      drove gain changes. The background had no effect on, or slightly reduced,
      adaptation. We conclude that the saccade adaptation mechanism is driven almost
      entirely by stimuli on or near the fovea and is affected very little by visual
      stimuli falling more peripherally.

PMID- 10927122
TI  - Changes in blood-retinal barrier permeability in form deprivation myopia in tree
      shrews.
AB  - To study the correlation between blood-retinal barrier (BRB) permeability and
      development of form deprivation (FD) myopia, FD was induced in tree shrews. The
      refractive error and the axial dimensions of the optical elements were measured.
      Ocular fluorescence was measured before and after fluorescein-Na injection. The
      inward permeability (P(in)) of the BRB was measured before and 15, 30, and 45
      days after FD was induced. FD eyes became significantly myopic 15 days after FD
      was induced (P<0.01), and myopia progressed 45 days after FD was induced compared
      with untreated controls. Neither anterior chamber length nor lens thickness
      changed significantly. The vitreous chamber in FD eyes, however, was
      significantly elongated from 15 days after FD was induced (P<0.01) compared with
      controls. The P(in) ratio (P(in) [FD eye]/P(in) [untreated control]), increased
      significantly 45 days after FD was induced (P<0.05). In FD myopia in tree shrews,
      the BRB permeability increases abnormally. Impaired BRB function might be a
      secondary effect of myopia development rather than the cause of myopia.

PMID- 10927123
TI  - Detection of the genotoxicity of air pollutants in and around the city of Sao
      Paulo (Brazil) with the Tradescantia-micronucleus (Trad-MCN) assay.
AB  - Tradescantia pallida cv. purpurea, a popular garden plant in Brazil, was used for
      the Tradescantia micronucleus (Trad-MCN) assay. In situ monitoring of the
      genotoxicity of air pollutants was carried out by sentinel approach, using the
      plant grown in the field or using the plants in pots which were carried to the
      monitoring sites. Two highly polluted sites, in Sao Paulo city (Cerqueira Cesar
      and Congonhas) and two rural sites (the cities of Pirassununga, 200 km and
      Caucaia do Alto, 50 km from Sao Paulo, respectively) were chosen for this study,
      in order to determine the gradient difference of the air pollution levels.
      Sentinel plants in Congonhas site presented the highest frequency of micronuclei
      (4.4%), in comparison with 2.2 and 2.3% found in plants from Pirassununga and
      Cerqueira Cesar sites, respectively (Kruskal-Wallis; P<0.020). Significant
      increases (F test; P<0.0001) in the frequency of micronuclei were observed in
      plants exposed in the polluted urban sites (Cerqueira Cesar: 5.7%; Congonhas:
      7.1% and Caucaia do Alto: 2.3%). The increase in the frequency of micronuclei
      observed indicates the potential risk of mutagenicity in presence of high
      concentrations of pollutants.

PMID- 10927124
TI  - Uptake kinetics of 99Tc in common duckweed.
AB  - The uptake of the nuclear waste product technetium-99 was studied in common
      duckweed (Lemna minor). In addition to measurements, a model involving two
      compartments in duckweed with different chemical forms of technetium was derived.
      The model was tested by chemical speciation, i.e. differentiating between reduced
      Tc-compounds and Tc(VII)O(4)(-). The TcO(4)(-) concentrations measured were in
      good agreement with those predicted by the model. Two processes determine
      technetium uptake: (1) transport of Tc(VII)O(4)(-) across the cell membrane, and
      (2) reduction of Tc(VII). The TcO(4)(-) concentration in duckweed reaches a
      steady state within 2 h while reduced Tc-compounds are stored, as a result of
      absence of release or re-oxidation processes. Bioaccumulation kinetic properties
      were derived by varying 99Tc concentration, temperature, nutrient concentrations,
      and light intensity. The reduction of technetium in duckweed was highly
      correlated with light intensity and temperature. At 25 degrees C the maximum
      reduction rate was observed at light intensities above 200 umol m(-2) s(-1) while
      half of the maximum transformation rate was reached at 41 umol m(-2) s(-1).
      Transport of TcO(4)(-) over the cell membrane requires about 9.4 kJ mol(-1),
      indicating an active transport mechanism. However, this mechanism behaved as
      first-order kinetics instead of Michaelis-Menten kinetics between 1x10(-14) and
      2.5x10(-5) mol l(-1) TcO(4)(-). Tc uptake could not be inhibited by 10(-3) mol l(
      1) nitrate, phosphate, sulphate or chloride.

PMID- 10927125
TI  - The impact of season of harvest and duration of pre-measurement storage impact
      hydraulic conductance of stem samples for Acer rubrum L. x saccharinum L. and
      Fraxinus americana L.
AB  - The influence of pre-measurement storage length and season of harvest of stem
      segment samples on hydraulic conductance and percentage embolism was determined
      for two tree species because no published guidelines exist concerning storage.
      Stem sections from Fraxinus americana L. 'Autumn Applause' (white ash) and Acer
      rubrum L. x saccharinum L. 'Autumn Blaze' (hybrid red maple) were collected from
      well-established trees in fall 1995 (October), spring 1996 (April), and summer
      1996 (July). Ends of stem sections collected in the fall were either covered with
      wax or left exposed. Entire sections from all dates were placed in closed plastic
      bags to prevent desiccation during transport and subsequent storage. Stem
      sections were either analyzed immediately (0 storage) or held at 2 degrees C for
      2 or 4 days. Hydraulic conductance before embolisms were cleared with positive
      pressure (initial k(h)), hydraulic conductance after embolisms were cleared
      (maximum k(h)), and percentage embolism were similar for all pre-embolism
      measurement storage lengths within each of the three seasonal sampling periods
      for hybrid red maple and spring- and summer-collected white ash. Fall-collected
      white ash samples with 0 storage had higher initial k(h), and percentage embolism
      increased if samples were stored. Embolism was greatest for summer-collected
      samples and lowest for spring-collected samples for hybrid red maple, but values
      were similar for white ash. Stem covering did not influence measured parameters.
      Our data indicate that hybrid red maple stem segments can be stored without
      significant loss of hydraulic conductance for up to 4 days, but white ash should
      not be stored in the fall. Unless maximum levels of native embolism have been
      reached, as determined from laboratory analysis, stem segments of species on
      which storage data are not available should be processed as soon as possible.

PMID- 10927126
TI  - Leaf gas exchange and solute accumulation in the halophyte Salvadora persica
      grown at moderate salinity.
AB  - The domestication of halophytes has been proposed as a strategy to expand
      cultivation onto unfavorable land. However, halophytes mainly have been
      considered for their performance in extremely saline environments, and only a few
      species have been characterized in terms of their tolerance and physiological
      responses to moderately high levels of salinity. Salvadora persica is an
      evergreen perennial halophyte capable of growing under extreme conditions, from
      very dry environments to highly saline soils. It possesses high potential
      economic value as a source of oil and medicinal compounds. To quantify its
      response to salinity, S. persica seedlings were exposed to 200 mM NaCl for 3
      weeks, and growth, leaf gas exchange and solute accumulation were measured. The
      presence of NaCl induced a 100% increase in fresh weight and a 30% increase in
      dry weight, relative to non-salinized controls. Increases in fresh weight and dry
      weight were not associated with higher rates of net CO(2) assimilation, however.
      Analysis of ion accumulation revealed that S. persica leaves accumulated Na(+) as
      a primary osmoticum. The concentration of Na(+) in leaves of salinized plants was
      approximately 40-fold greater than that measured in non-salinized controls, and
      this was associated with significant reductions in leaf K(+) and Ca(2+)
      concentrations. In addition, a significant accumulation of proline, probably
      associated with osmotic adjustment and protection of membrane stability, occurred
      in roots of salinized plants.

PMID- 10927127
TI  - Growth responses to ozone in plant species from wetlands.
AB  - Ten wet grassland species were fumigated with four concentrations of ozone
      (charcoal-filtered air, non-filtered air and non-filtered air plus 25 or 50 nl l(
      1) ozone) in open-top chambers during one growing season to investigate the long
      term effect of this air pollutant on various growth variables. Only Eupatorium
      cannabinum showed ozone-related foliar injury, while five species reacted with
      significantly ozone-enhanced senescence. Premature senescence was paralleled by a
      significant ozone-induced reduction of green leaf area in Achillea ptarmica, E.
      cannabinum and Plantago lanceolata. At the intermediate harvest performed after
      28 days shoot weights were significantly decreased by ozone in A. ptarmica and
      increased in Molinia caerulea. At the final harvest performed at the end of the
      growing season two other species, Cirsium dissectum and E. cannabinum had a
      significantly reduced shoot weight due to ozone. Root biomass was determined only
      at the intermediate harvest. The root:shoot ratio (RSR) was significantly reduced
      in C. dissectum, while it increased in M. caerulea. Seven of the species
      developed flowers during the experiment. While no significant ozone effects on
      flowering date and flower numbers were detected, flower weights were
      significantly reduced in E. cannabinum and P. lanceolata.

PMID- 10927128
TI  - Fungicides cytotoxicity expressed in male gametophyte development in Brassica
      campestris after in vitro application of converted field doses.
AB  - A simple method to determine the toxicity of fungicides on male gametophyte in
      Brassica campestris subsp. oleiferae is described. The calculation of fungicide
      concentration used in the test is derived from doses used in field application.
      The expression of regression curves and calculation of regression equations
      require the logarithmic transformation of fungicide concentration. The range of
      the sensitivity of the method is very wide. The minimal concentration detected as
      significantly different from control ranges from 1.7 to 7.0 pg of the active
      compound. Fungicides declared as non-toxic for plants in field tests were
      cytotoxic for male gametophyte development. The synergistic action of more than
      one active compound resulted in higher toxicity.

PMID- 10927129
TI  - Effect of kinetin concentration and methods of application on seed germination,
      yield components, yield and fiber properties of the Egyptian cotton (Gossypium
      barbadense).
AB  - Two field experiments in 1993 and 1994 as well as a laboratory germination
      experiment were conducted on the Egyptian cotton cultivar Giza 75 (Gossypium
      barbadense) to determine the effect of six concentrations of kinetin (6
      furfurylaminopurine) ranging from 0 to 10.0 mg l(-1) and three different methods
      of application: (A) seeds were soaked for 24 h before germination (laboratory
      experiment) or sowing (field experiment) in solutions of different kinetin
      concentration, (B) cotton plants were sprayed twice with different kinetin
      concentrations at 60 and 75 days after sowing (DAS) during the square initiation
      and the beginning of bolling stages, at volume solution of 480 l ha(-1). (C)
      Seeds were soaked in kinetin solutions before sowing as method A. In addition
      cotton plants were sprayed twice as method B with the same kinetin
      concentrations. Kinetin application improved seed viability and seedling vigour
      as shown by lengths of the hypocotyl, radicle and the entire seedling, as well as
      seedling fresh weight. Moreover, significant increases were recorded in the
      number of open bolls/plant, boll weight, lint and seed indices, seed cotton
      yield/plant, and seed cotton and lint yields/plot. The highest means were
      obtained at 5 mg kinetin l(-1) concentration and under method C of application.
      Treatments generally, had no significant effects on lint percentage, yield
      earliness and fiber properties. These results show that, the use of kinetin at 5
      mg l(-1) for pre-soaking seeds before planting and spraying cotton plants at 60
      and 75 DAS with the same concentration could improve cotton germination, seed
      cotton and lint yields.

PMID- 10927130
TI  - Impacts of urban levels of ozone on Pinus halepensis foliage.
AB  - Between May and September, 1996, seedlings of Pinus halepensis were placed at a
      site adjacent to an automated air pollution monitoring station within the urban
      area of Florence. Additional 'control' plants were placed in chambers ventilated
      with charcoal/Purafil(R)-filtered air. All trees were well watered throughout the
      whole experimental period. During the exposure period, ambient levels of sulphur
      dioxide were very low, whilst the accumulated hourly exposure to ozone above 40
      ppb (i.e. AOT40) exceeded 20000 ppb h(-1) - peak hourly ozone concentrations
      rising to levels above 100 ppb. Trees exposed to ambient levels of air pollution
      exhibited typical symptoms of ozone damage (chlorotic mottle) on previous year
      needles toward the end of the summer. Similar symptoms were not observed on
      equivalent trees exposed to filtered-air, nor were visible symptoms accompanied
      by insect or pest infestation. Anatomical and ultrastructural observations made
      on symptomatic needles revealed degeneration in mesophyll cells bordering sub
      stomatal cavities and alterations in chloroplast ultrastructure (fat
      accumulation, starch and tannin pattern modifications). These observations are
      consistent with the known effects of air pollutants (namely ozone) recorded in
      the literature. Findings are discussed in relation to the impacts of ozone on P.
      halepensis in the Mediterranean region.

PMID- 10927131
TI  - Changes of reliability and efficiency of micronucleus bioassay in Vicia faba
      after exposure to metal contamination for several generations.
AB  - Mitotic root micronucleus (MCN) frequency in Vicia faba as a bioassay, is
      primarily based on the extent of the sentinel Vicia response in terms of
      cytogenetic damage quantitatively or qualitatively to indicate the presence of
      mutagenic contaminants. This paper describes an investigation designed to assess
      changes in MCN frequencies of Vicia faba from three generation plants obtained,
      respectively from a reference site (RS) and a metal-contaminated experimental
      field (EF) in the bioassay of mutagenic Cd(2+) and NaN(3). The background value,
      dose-response to Cd(2+) and to NaN(3) in three generation (F(1), F(2) and F(3))
      plants of the EF and the initial (F(0)) plants were determined in terms of MCN
      frequencies. With more generations of growing Vicia plants in the EF, a higher
      background value of MCN frequency, a lower slope value in the regression
      equation, a smaller ratio of MCN frequency between the control and treatment in
      the same generation and larger perturbation values were observed. This denotes
      that the decreased reliability and efficiency are represented in Vicia plants
      from the EF if the plants are used as sentinels in the bioassay of mutagenic
      Cd(2+) and NaN(3). It was concluded that the Vicia MCN bioassay should be used as
      an endpoint biomarker acceptable in biomonitoring environmental mutagens when the
      sentinel plants were collected from clean areas. Because no place is absolutely
      without pollutants, it is suggested that several seed stock centers should be
      established for providing sentinel Vicia if Vicia MCN bioassay is used as a
      biomarker to identify the global environmental status.

PMID- 10927132
TI  - Selection and delineation of lymph node target volumes in head and neck conformal
      radiotherapy. Proposal for standardizing terminology and procedure based on the
      surgical experience.
AB  - The increasing use of 3D treatment planning in head and neck radiation oncology
      has created an urgent need for new guidelines for the selection and the
      delineation of the neck node areas to be included in the clinical target volume.
      Surgical literature has provided us with valuable information on the extent of
      pathological nodal involvement in the neck as a function of the primary tumor
      site. In addition, few clinical series have also reported information on
      radiological nodal involvement in those areas not commonly included in radical
      neck dissection. Taking all these data together, guidelines for the selection of
      the node levels to be irradiated for the major head and neck sites could be
      proposed. To fill the missing link between these guidelines and the 3D treatment
      planning, recommendations for the delineation of these node levels (levels I-VI
      and retropharyngeal) on CT (or MRI) slices have been proposed using the
      guidelines outlined by the Committee for Head and Neck Surgery and Oncology of
      the American Academy for Otolarynology-Head and Neck Surgery. These guidelines
      were adapted to take into account specific radiological landmarks more easily
      identified on CT or MRI slices than in the operating field.

PMID- 10927133
TI  - Target volumes in radiotherapy for high-grade malignant glioma of the brain.
AB  - Delineation of the clinical target volume (CTV) in radiation treatment planning
      of high-grade glioma is a controversial issue. The use of computerized tomography
      (CT) and magnetic resonance imaging (MRI) has greatly improved the accuracy of
      tumor localization in three-dimensional planning. This review aims at critically
      analyzing available literature data in which tumor extent of high-grade glioma
      has been assessed using CT and/or MRI and relating this to postmortem
      observations. Attention is given to the pattern of tumor spread at initial
      presentation and to tumor recurrence pattern after external beam irradiation.
      Special emphasis is given to the site of tumor regrowth after radiation treatment
      in relation to the boundaries of the CTV. Guidelines for delineating CTV will be
      inferred from this information, taking data on radiation effects on the normal
      brain into account.

PMID- 10927134
TI  - The impact of three-dimensional radiation on the treatment of non-small cell lung
      cancer.
AB  - PURPOSE: Non-small cell lung cancer (NSCLC) patients with locally advanced
      unresectable disease have a grim prognosis. Radiotherapeutic strategies are
      necessary to improve the permanent eradication of thoracic disease. The poor
      results achieved with conventional external beam radiation therapy reflect in
      part, the inadequacy of such therapy in achieving its primary objective of
      achieving local control. The impact of three-dimensional conformal radiation
      therapy (3-DCRT) on local disease eradication and its potential role in improving
      survival is assessed. DESIGN: This review addresses aspects of the software and
      hardware technology of 3-DCRT, the clinical and technical aspects of target
      volume definition, the use of 3-DCRT to predict radiation pneumonitis, strategies
      for dose escalation in NSCLC, and analyses the clinical results to date. RESULTS:
      Initially investigators compared the best treatment techniques devised with
      conventional planning techniques to those devised with 3-DCRT. These analyses
      showed that 3-DCRT had the potential to deliver high dose radiation (>70 Gy) with
      minimal underdosing and with a concomitant relative sparing of normal tissues.
      This technical demonstration of enhanced therapeutic ratio is the basis for the
      evolving clinical utilization of 3-DCRT for NSCLC. Software and hardware
      developments continue to develop and have the potential to solve evolving
      clinical issues. Dose-volume-histograms have been used to accurately quantify
      lung dose and derived parameters have the potential to predict the risk of
      pneumonitis for individual patients before treatment. Initial clinical results
      have been promising and strategies for further dose escalation are emerging.
      CONCLUSION: Preliminary experience has resulted in promising survival following
      three-dimensional conformal radiation therapy alone for locally advanced NSCLC.
      More follow-up and experience will determine late toxicity, maximum dose, and
      efficacy of dose escalation with three-dimensional conformal radiation therapy.
      Strategies should be developed to integrate this modality into the combined
      treatment of locally advanced non-small cell lung cancer.

PMID- 10927135
TI  - Combined chemoradiotherapy with daily low-dose cisplatin in locally advanced
      inoperable non-small cell lung cancer.
AB  - Sixty-one consecutive patients with locally advanced inoperable non-small-cell
      lung cancer were treated with chemoradiation with 60 Gy and concomitant daily low
      dose cisplatin (6 mg/m(2)) in a single uninterrupted course. Toxicity was mild,
      80% of patients were treated as outpatients. The median survival of 70 weeks
      compares favorably to the literature.

PMID- 10927136
TI  - Effect of pentoxifylline on radiation response of non-small cell lung cancer: a
      phase III randomized multicenter trial.
AB  - PURPOSES: The objectives of this prospective clinical trial were to determine
      whether pentoxifylline improves the radiation response and survival in patients
      with non-small cell lung cancer. MATERIALS AND METHODS: From July 1993 through
      October 1994, 64 patients with histologically confirmed Stage I, II and III non
      small cell lung cancer were randomly divided into pentoxifylline
      (Pento)+Radiotherapy (RT) group and RT alone group. Out of the 64 patients, only
      47 patients who had measurable tumors on chest X-ray views were analyzed and
      divided into Pento+RT group (n=27) and RT alone group (n=20). Total tumor dose of
      65-70 Gy was delivered as conventional fractionated radiation schedules. Pento
      was given to the patients 3 x 400 mg/day with a daily dose of 1200 mg during RT.
      RESULTS: Complete response (CR), partial response (PR), and stable in Pento+RT
      group were three (11%), 13 (48%), and 11 (41%), respectively, as compared with
      corresponding values of three (15%), 13 (65%), and four (20%) in the RT alone
      group. The median time to relapse in the Pento+RT group was 11 months which was 2
      months longer than for the RT alone group (P>0.05). All the patients in both
      groups showed lower than or equal to grade 2 dysphagia, odynophagia, pulmonary
      fibrosis, and pneumonitis. The median survival was 18 months in the Pento+RT
      group and 7 months in the RT alone group. The 1-year survival rate was 60% in the
      Pento+RT group and 35% in the RT alone group, the 2-year survival rate was 18% in
      the Pento+RT group and 12% in the RT alone group. But these differences were not
      statistically significant (P>0.05). CONCLUSION: We concluded that Pento is a
      modestly effective radiation response modifier and provide benefit in the
      treatment of non-small cell lung cancer.

PMID- 10927137
TI  - Beam intensity modulation for penumbra enhancement and field length reduction in
      lung cancer treatments: a dosimetric study.
AB  - BACKGROUND AND PURPOSE: In a recent treatment planning study, a previously
      published technique for superior-inferior field length reduction for prostate
      cancer patients, based on penumbra enhancement using static beam intensity
      modulation (BIM) with a multileaf collimator, was investigated for lung cancer
      treatments. For the patient group studied, the field lengths could be reduced by
      1.4 cm and an average dose escalation of 6 Gy (maximum 16 Gy) appeared to be
      possible without any increase in the calculated risk of radiation pneumonitis.
      However, this planning study was performed with a treatment planning system that
      does not correctly account for the increased lateral secondary electron transport
      in lung tissue, resulting in too steep beam penumbrae. Therefore, prior to
      clinical implementation, an extensive dosimetric study was performed to evaluate
      and optimize BIM for penumbra enhancement and superior-inferior field length
      reduction in lung cancer treatments. MATERIALS AND METHODS: Film dosimetry was
      performed in several phantoms consisting of water equivalent and lung equivalent
      materials, both for a 6 and a 10 MV photon beam. Measured dose distributions were
      used to (i) adapt the BIM technique to properly account for increased lateral
      secondary electron transport, (ii) compare BIM dose distributions in lung
      material with dose distributions of standard treatment fields, and (iii)
      investigate the use of our treatment planning system for the design of BIM plans
      for lung cancer patients. RESULTS: Compared with our treatment planning study the
      superior and inferior boost fields, used in the BIM technique for penumbra
      enhancement, had to be longer and of a higher weight to compensate for the
      increased lateral secondary electron transport in lung tissue. With these
      modifications in the BIM technique, field lengths could indeed be reduced by 1.4
      cm compared with treatment with standard fields, without the appearance of
      underdosages in the most superior and inferior target areas, whilst better
      sparing the healthy lung tissue. Practical rules were derived to use our
      treatment planning system for the design of BIM treatment plans. CONCLUSIONS: In
      spite of the increased lateral secondary electron transport in lung tissue,
      static BIM with a multileaf collimator may effectively be used for penumbra
      enhancement and superior-inferior field length reduction in lung cancer
      treatments.

PMID- 10927138
TI  - The treatment results of 40 patients with localized endobronchial cancer with
      external beam irradiation and intraluminal irradiation using low dose rate
      (192)Ir thin wires with a new catheter.
AB  - BACKGROUND AND PURPOSE: While bronchial intraluminal irradiation is valued highly
      as a useful palliative treatment for lung cancer, its role as a curative
      treatment is unclear. The treatment results of 40 localized enbobronchial tumors
      (including tracheal cancer) who underwent external beam irradiation (EBR) and
      intraluminal irradiation (IR) as a curative treatment is reported, and the role
      of combined EBR and IR as a curative potential treatment is examined. MATERIALS
      AND METHODS: Forty patients, including 22 with roentgenographically occult lung
      cancer (ROLC), 14 (18 lesions) with postoperative recurrent lung cancer (PORLC)
      and four with tracheal cancer, who underwent EBR and IR from February 1987 to
      August 1996, were studied. IR was conducted using low dose rate (1.48 GBq)
      (192)Ir thin wires at a bronchial mucosal dose of 4-6 Gy per fraction, with a
      total dose of 10-57 Gy (median 28 Gy). All patients were also given combined
      external Linac X-ray irradiation for a total dose of 30-77 Gy (median 52 Gy).
      RESULTS: As for the primary effect, complete response (CR) was obtained in all 22
      ROLC cases; CR was obtained in 12 (16 lesions), partial response (PR) in one and
      minor response (MR) in one of the PORLC cases; and CR was obtained in three and
      PR in one of the tracheal cancer cases. The 3-year and 5-year local control rate
      by Kaplan-Meier method was 75 and 65%, respectively. Twenty-two patients survived
      for 3 years or longer. Complications included one case each of fatal tracheal
      hemorrhage, bronchial mucosal ulcer and bronchial stenosis. CONCLUSIONS: Combined
      EBR and IR is useful as a curative potential treatment, and long-term survival
      can be expected in ROLC, tracheal cancer and a portion of PORLC cases.

PMID- 10927139
TI  - Cell proliferation and apoptosis in stage III inoperable non-small cell lung
      carcinoma treated by radiotherapy.
AB  - PURPOSE: The purpose of this study was to assess the prognostic value of the
      expression of p53 and bcl-2, the apoptotic index and the expression of
      topoisomerase II alpha in patients with inoperable non-small cell lung cancer
      (NSCLC) treated with high dose radiotherapy. PATIENTS AND METHODS: A number of
      161 patients with inoperable NSCLC treated with high dose radiotherapy (60 Gy)
      were included. Immunohistochemical analysis was used to assess the expression of
      nuclear p53-protein, topoisomerase II alpha and cytoplasmatic expression of bcl
      2, while spontaneous apoptosis was assessed using in situ labeling. The minimal
      follow up period was 2 years. RESULTS: Local control did not only depend on the
      presence of p53 expression, but also on the proportion of p53 positive cells. The
      most important prognostic factor was the apoptotic index. A high apoptotic index
      was associated with worse local control, more distant metastases and a
      significantly worse overall survival. No association was noted between the
      expression of bcl-2 and topoisomerase II alpha with any of the endpoints.
      CONCLUSION: This study indicates that p53 expression and the apoptotic index are
      prognostic factors with regard to local control in patients with inoperable NSCLC
      treated with radiotherapy and by combining these 2 factors, a clinically relevant
      estimation of the local control probability can be made. The apoptotic index
      turned out to be the only factor significantly related to survival.

PMID- 10927140
TI  - Radiation techniques for head and neck tumors.
AB  - PURPOSE: A technique that combines some advantages of conforming techniques for
      advanced oro- and hypopharyngeal carcinomas is proposed. The aim is to increase
      the dose homogeneity in the target volume relative to lateral opposed fields.
      METHODS AND MATERIALS: This publication compares conforming radiation techniques
      based on standard equipment, standard linear accelerator setup and commercially
      available planning software with lateral opposed fields. More advanced conformal
      techniques reported in the literature are taken into account in a semi
      quantitative manner. Our standard method uses an arc rotation, sparing the spinal
      cord. In contrast to earlier methods of this type, the resulting dose deficit in
      the vicinity of the spine is compensated by static lateral wedged fields. Dose
      distributions for 25 consecutive patients were planned. RESULTS: The conforming
      techniques were found to produce more homogeneous dose distributions than lateral
      opposed fields. In the planning target volume (PTV) (mean: 940 cm(3)) a standard
      deviation of dose of 4.6% was achieved. Ninety-five percent of the PTV were
      enclosed by the 90% isodose. The maximal spinal cord dose was limited to 45 Gy.
      The dose distributions of these techniques could compete with literature data on
      advanced techniques (the published dose-volume histogram (DVHs) of PTVs were
      evaluated). At the linear accelerator time for realization took 14 min on
      average. The planning time is 1-4 h (mean: less than 2 h). CONCLUSION: A
      rotational technique applicable with standard equipment is presented. Dose
      coverage of target volumes is improved, while the spinal cord is spared.

PMID- 10927141
TI  - The role of radiotherapy in treating squamous cell carcinoma of the external
      auditory canal, especially in early stages of disease.
AB  - PURPOSE: Our intent was to investigate the role of radiotherapy in treating
      external auditory canal squamous cell carcinoma, especially in early stages of
      disease. MATERIALS AND METHODS: The treatment results for 20 patients treated
      between 1980 and 1998 were retrospectively analyzed. Radiotherapy was used as an
      initial treatment without surgery in eight patients and with surgery in 12
      patients. The patients treated by radiotherapy alone received 65 Gy in 26
      fractions over 6.5 weeks. The patients treated with radiotherapy perioperatively
      received 30-75 Gy in 12-30 fractions. The follow-up period for survivors
      including patients died of intercurrent disease ranged from 7 to 205 months
      (mean: 71 months). RESULTS: The 5-year survival rate calculated by the Kaplan
      Meier method for all patients was 59%. According to Stell classification
      (Laryncol. Otol. 99 (1985) 847), the 5-year survival rates for eight patients
      with T1 disease and eight with T2 disease were 100 and 38%, respectively. In the
      eight patients with T1 disease, disease control was 100%. Local control with
      hearing preservation was achieved in five patients with T1 disease by
      radiotherapy alone. No late complications related to radiotherapy were observed.
      CONCLUSIONS: A precise diagnosis of the disease in terms of whether or not it has
      invaded the bone is important in order to predict the treatment outcome.
      Radiotherapy with or without surgery is the treatment of choice for patients with
      T1-stage disease. Surgery with radiotherapy is recommended as standard care for
      tumors with bony invasion.

PMID- 10927142
TI  - Conformal three-dimensional photon radiotherapy for paranasal sinus tumors.
AB  - BACKGROUND: Tumors in the nasal cavity and paranasal sinus are difficult to treat
      with radiotherapy. Usually, in addition to a two- or three-field photon
      technique, an interorbital electron field is required. This may result, however,
      in severe over- or underdosage, the latter being especially detrimental when
      occurring in the main tumor bulk. METHODS AND RESULTS: We present a conformal
      three-dimensional treatment technique that provides sufficient interorbital dose
      with photons only while sparing the eyes, optic nerves and chiasm, and may be
      considered for selected tumors in this region.

PMID- 10927143
TI  - Accelerated hyperfractionated radiotherapy in supratentorial malignant
      astrocytomas.
AB  - PURPOSE: To determine the safety and effectiveness of accelerated
      hyperfractionated radiotherapy in the treatment of supratentorial malignant
      astrocytomas. MATERIALS AND METHODS: Between June 1995-July 1997, 75 patients
      were enrolled to a prospective phase II study. A total dose of 60 Gy was
      delivered in 2 Gy b.i.d. fractions with an interval of 6-8 h, 5 days per week, in
      an overall time of 3 weeks. The treatment protocol was planned to give 40 Gy to a
      treatment volume covering the contrast-enhancing lesion and oedema (+ 3-cm
      margin) and additional 20 Gy to the volume encompassing the contrast-enhancing
      lesion alone with a 1-cm margin based on preoperative magnetic resonance imaging
      and/or CT findings. The patients had a median age of 46 years and a median
      Karnofsky performance status score of 80. Histology consisted of anaplastic
      astrocytoma (AA) in 16 (21%) and glioblastoma multiforme (GBM) in 59 (79%)
      patients. RESULTS: Median survival was 11 months for all patients; 10 months for
      GBM patients and 40 months for AA patients. Survival rates at 1 and 3 years were
      41%, 11% for all patients; 62, 37% for AA patients and 35, 6% for GBM patients,
      respectively. Multivariate analysis revealed significant impact of age, histology
      and neurological functional class on survival. The incidence of grade 3 or worse
      late neurological toxicity was 5.3%. CONCLUSIONS: Although accelerated
      hyperfractionated radiotherapy showed no significant advantage on survival, it
      shortened the treatment period from 6 to 3 weeks. Radiotherapy was well tolerated
      and the incidence of late toxicity is acceptable.

PMID- 10927144
TI  - Can p53 alterations be used to predict tumour response to pre-operative chemo
      radiotherapy in locally advanced rectal cancer?
AB  - PURPOSE: To examine whether p53 tumour suppressor gene alterations can be used to
      predict tumour response to pre-operative chemo-radiation in locally advanced
      rectal cancer in terms of reduction in tumour size and local failure. METHODS:
      p53 alterations were studied in pre-treatment biopsy specimens of rectal
      carcinomas from 48 patients by immunohistochemistry (IHC) and polymerase chain
      reaction/single strand conformation polymorphism (PCR-SSCP) gene mutation
      analysis. Pre-operative pelvic radiotherapy was delivered with four fields, 45 Gy
      to the ICRU point in 25 fractions over 5 weeks. A radio-sensitising dose of 5
      fluorouracil (500 mg/m(2)) was delivered concurrently for 6 days of the 5-week
      schedule (days 1, 2, 3 and days 22, 23 and 24). Total meso-rectal excision was
      planned 4 to 6 weeks from completion of pre-operative treatment. Response to
      therapy was assessed by macroscopic measurement of the surgical specimen by a
      pathologist who was unaware of the pre-treatment tumour size or of the p53
      status. RESULTS: IHC evidence of p53 protein accumulation was found in 40% of
      tumours, p53 gene mutation in 35% and p53 alteration (either or both changes) in
      46%. The average reduction in tumour size was 53% in the group with 'wild-type'
      p53 (IHC-/SSCP-) and 63% in the group with altered p53 (either IHC+ or SSCP+;
      P=0.18). No significant differences in tumour size reduction or local failure
      were observed in the groups with p53 overexpression or p53 mutation compared with
      normal. CONCLUSIONS: p53 alteration detected by IHC or SSCP analysis is not a
      clinically useful predictor of local response to pre-operative adjuvant therapy
      in advanced rectal carcinoma.

PMID- 10927145
TI  - Effects of mitomycin C on the oxygenation and radiosensitivity of murine and
      human tumours in mice.
AB  - BACKGROUND AND PURPOSE: Mitomycin C was one of the first chemotherapeutic agents
      to be shown to have preferential cytotoxicity toward hypoxic cells in vitro.
      Consequently, it has been used clinically with radiotherapy, and has stimulated
      considerable interest for analogue development. More recent studies also
      suggested a possible role for the drug in enhancing tumour blood flow; we
      therefore undertook a comprehensive examination of mitomycin C as a potential
      radiosensitizer in murine and human tumours growing in mice. MATERIALS AND
      METHODS: Two dissimilar human tumour xenograft systems, SiHa and WiDr cells, were
      used as was the murine SCCVII line. Effects of mitomycin C treatment on the
      regional and microregional blood flow in these tumours was evaluated, and cell
      sorting based on dye perfusion techniques was used to study the cytotoxicity of
      mitomycin C as a single agent or in combination with radiation in the xenograft
      systems. RESULTS: Contrary to our expectations, no preferential killing of less
      well oxygenated tumour cells in situ was observed, nor were any consistent
      effects on tumour blood flow found. The inclusion of mitomycin C with radiation
      did, however, produce a modest increase in cell killing in the hypoxic
      subpopulations of the xenograft system with the largest hypoxic fraction.
      CONCLUSIONS: Our results indicate that combined treatment with mitomycin C and
      radiation cannot be rationalized on the expectation of either complementary
      cytotoxicity of the modalities, or of drug-induced improvement in tumour
      oxygenation.

PMID- 10927146
TI  - The effect of nicotinamide on spontaneous and induced activity in smooth and
      skeletal muscle.
AB  - BACKGROUND AND PURPOSE: Nicotinamide (NA) is currently undergoing clinical trials
      as a tumour radiosensitizer. The dose that can be administered is currently 80
      mg/kg per day, but this may be restricted to 60 mg/kg per day by the high
      incidence of nausea and vomiting. To investigate some of NA's underlying
      mechanisms of action, we have used an ex vivo system to study the direct effect
      of this drug, over a wide range of concentrations, on isolated spontaneously
      active rat ileum. Effects on the gut were compared with the action of NA on
      skeletal and vascular smooth muscle. MATERIALS AND METHODS: Isolated rat ileum
      rings were perfused with oxygenated Krebs' solution in an organ bath. NA (1
      microM to 10 mM) was introduced to the perfusate and the change in amplitude of
      spontaneous peristaltic activity recorded. Dissected frog sartorius muscle was
      bathed in modified oxygenated Ringer's solution in an organ bath. The muscle was
      electrically stimulated to generate isometric contractions. Tension was then
      measured before and after the addition of a range of NA concentrations (8.2-24.6
      mM) to the organ bath. RESULTS: NA inhibited peristalsis in the ileum in a dose
      dependent manner. At a drug concentration of 1 mM the amplitude of contractions
      was reduced to <50% of the initial control value. NA had no effect on the
      electrically induced contractions in the isolated frog sartorius muscle.
      CONCLUSIONS: Gut smooth muscle is highly sensitive to the relaxant effect of NA
      producing 50% relaxation at a concentration approximately 10 fold lower than that
      required in rat arterial smooth muscle, while having no effect on non-mammalian
      skeletal smooth muscle. This may provide explanations for the occurrence of
      emesis in patients undergoing combined nicotinamide therapies and highlight
      possible alternatives available to counter this unwanted side-effect.

PMID- 10927148
TI  - Radiosensitivity of human pancreatic cancer cells in vitro and in vivo, and the
      effect of a new hypoxic cell sensitizer, doranidazole.
AB  - BACKGROUND AND PURPOSE: A clinical study of the new 2-nitroimidazole nucleoside
      analogue doranidazole (PR-350) in combination with intraoperative radiotherapy is
      ongoing in Japan for localized unresectable pancreatic cancer. However, few data
      have been reported on the radiosensitivity and hypoxic fraction of human
      pancreatic cancers, and the efficacy of doranidazole against them. This study was
      undertaken to address these issues. MATERIALS AND METHODS: In vitro, four
      established human pancreatic cancer cell lines (SUIT-2, PANC-1, MIA PaCa-2 and
      BxPC-3) and murine SCCVII tumor cells (for comparison) were used. These cells
      were treated with 0.4 or 1 mM doranidazole for 45 mm prior to and during aerobic
      or hypoxic irradiation, and the cell survival was determined using the colony
      assay. In vivo, Balb/c nude mice bearing the pancreatic cancers (about 200 mg) on
      their backs received whole-body irradiation either after cervical dislocation,
      without physical restraint or anesthesia, or 20 min after intravenous injection
      of 100 mg/kg (0.4 mmol/kg) or 250 mg/kg (1 mmol/kg) of doranidazole. Following
      irradiation, the in vivo-in vitro assay was performed. The hypoxic fraction was
      estimated by the paired survival curve method. RESULTS: Regarding in vitro
      radiosensitivity, there were no characteristics common to the four pancreatic
      cancer cell lines. In vitro, doranidazole had no sensitizing effect under aerobic
      conditions, but under hypoxic conditions, its sensitizer enhancement ratio (SER)
      was 1.25-1.3 at 0. 4 mM and 1.4-1.55 at 1 mM against the four pancreatic cancer
      cell lines. These SERs were similar to those obtained in SCCVII cells. In vivo,
      the hypoxic fraction was 20% (95% CI, 11-38%) in SUIT-2, 14% (6.5-28%) in PANC-1,
      10% (5.9-16%) in MIA PaCa-2, and 27% (15-46%) in BxPC-3 tumors. The SER of
      doranidazole was 1.15-1.3 at the dose of 100 mg/kg and 1.35-1.45 at 250 mg/kg.
      CONCLUSIONS: The four xenografted human pancreatic cancers had hypoxic fractions
      of 10-27% (mean: 18%). Doranidazole had definite in vitro and in vivo effects on
      all pancreatic cancer cell lines.

PMID- 10927149
TI  - An automatic method for the evaluation of xenobiotic toxicity on haematopoietic
      progenitors.
AB  - Culture of haematopoietic progenitors is used in toxicology to evaluate the
      effects of xenobiotic contaminants on humans. One of the most important parts of
      this analysis is the quantification of cell aggregates in the culture. These
      aggregates can have different sizes and shapes, which reflect the category of
      cells (granulocyte or monocyte), and the growth percentage reflects the toxic
      effect of the contaminant. A proposal for an automatic method based on image
      analysis is described in this work. Algorithms able to solve the basic problems
      are proposed and tested, and the problem concerning a tridimensional analysis is
      exposed and discussed.

PMID- 10927147
TI  - Influence of dose per fraction and overall treatment time on the response of
      pulmonary micrometastases of the R1H-tumour to fractionated irradiation.
AB  - BACKGROUND AND PURPOSE: Macroscopic subcutaneously growing R1H-tumours have been
      shown to respond almost independently of the dose per fraction when treated under
      ambient conditions. In addition decelerated repopulation during fractionated
      irradiation has been shown for this experimental tumour. The aim of the present
      study was to investigate whether this is also the case for pulmonary
      micrometastases which are assumed to be fully oxygenated or whether differences
      in the oxygenation status of the tumour possibly alters its response to
      fractionation. The influence of the dose per fraction and overall treatment time
      on the response of micrometastases to fractionated irradiation was studied.
      MATERIALS AND METHODS: Pulmonary metastases were induced by i.v. injection of
      viable tumour cells. Treatment was started 14 days later, when metastases reached
      an average size of four cells. Total doses of 16 to 28 Gy were administered
      within an overall treatment time of 11 or 25 days, using doses per fraction of 1,
      2, or 4 Gy. Tumour response was quantified by metastatic control (MCD(37%)).
      RESULTS: Fractionation had a significant influence on local control (P=0.009).
      After application of 1, 2, or 4 Gy and an overall treatment time of 11 days the
      MCD(37%) was 25.4 (95% C.I.: 21.5-32.0) Gy, 20.7 (17. 0-24.0) Gy, and 18.5 (14.9
      21.6) Gy, respectively. When overall treatment time was prolonged to 25 days the
      MCD(37%) increased to 25. 5 (21.3-33.5) Gy when fractions of 2 Gy where applied,
      but this difference was not significant (P=0.13). The doubling time of 12.8 days
      determined for the metastatic clonogenic tumour cells during fractionated
      irradiation was significantly longer than the 4.1 days observed for untreated
      metastases (P=0.006). CONCLUSIONS: The results show a strong influence of
      fractionation on treatment outcome and a decelerated repopulation during
      fractionated irradiation treatment for well oxygenated pulmonary metastases of
      the R1H-tumour.

PMID- 10927151
TI  - Mann-Whitney/Wilcoxon's nonparametric cumulative probability distribution.
AB  - It is demonstrated how complete nonparametric, cumulative probability
      distributions for Mann-Whitney/Wilcoxon's nonparametric, two-sample test can be
      constructed based on algorithms published earlier in this journal. These
      procedures provide cumulative probabilities for all possible rank sums in the
      nonparametric two-sample test. Separate programs for MS(PC)-DOS and Macintosh
      computers are offered.

PMID- 10927150
TI  - Construction and visualisation of three-dimensional facial statistics.
AB  - This paper presents a new method for the construction of three-dimensional (3D)
      probabilistic facial averages and demonstrates the potential for applications in
      clinical craniofacial research and patient assessment. Averages are constructed
      from a database of registered laser-range scans and photographic images using
      feature based image warping. Facial features are extracted using a template of
      connected contours, adapted to each subject interactively using snakes. Each
      subject's images are warped to the average template shape and the mean depth,
      colour and covariance matrix is found at each point. Statistical comparison of
      individuals with an average or between two averages is visualised by converting
      the probabilities to a coloured texture map.

PMID- 10927152
TI  - Lumped parameter estimation for the embryonic chick vascular system: a time
      domain approach using MLAB.
AB  - We have evaluated several lumped parameter analog models for the early chick
      embryonic vascular system that may be used to infer loading characteristics of
      the developing heart. We measured dorsal aortic pressure and flow simultaneously
      with a servo-null pressure system and a pulsed Doppler velocimeter. Four
      different analog circuit models were chosen for comparisons. We formulated the
      time-domain differential equations specifying the relations between pressure and
      flow in the models, and then estimated the lumped parameters that produced the
      best fit. The MLAB mathematical modeling software was used for solving
      differential equations, and for minimizing the difference between model-predicted
      values and experimental data. The traditional three-element Windkessel model with
      an added inductance term was most often the best-fitting model. This is
      compatible with the previous study using a frequency-domain approach. The
      procedures developed for the current study are adaptable for the study of a
      variety of nonlinear models, and distributed parameter models for mammalian
      cardiovascular development with mechanically, pharmacologically, or genetically
      altered conditions.

PMID- 10927154
TI  - Simulation of axonal excitability using a Spreadsheet template created in
      Microsoft Excel.
AB  - The objective of this present study was to implement an established simulation
      protocol (A.M. Brown, A methodology for simulating biological systems using
      Microsoft Excel, Comp. Methods Prog. Biomed. 58 (1999) 181-90) to model axonal
      excitability. The simulation protocol involves the use of in-cell formulas
      directly typed into a spreadsheet and does not require any programming skills or
      use of the macro language. Once the initial spreadsheet template has been set up
      the simulations described in this paper can be executed with a few simple
      keystrokes. The model axon contained voltage-gated ion channels that were modeled
      using Hodgkin Huxley style kinetics. The basic properties of axonal excitability
      modeled were: (1) threshold of action potential firing, demonstrating that not
      only are the stimulus amplitude and duration critical in the generation of an
      action potential, but also the resting membrane potential; (2) refractoriness,
      the phenomenon of reduced excitability immediately following an action potential.
      The difference between the absolute refractory period, when no amount of stimulus
      will elicit an action potential, and relative refractory period, when an action
      potential may be generated by applying increased stimulus, was demonstrated with
      regard to the underlying state of the Na(+) and K(+) channels; (3) temporal
      summation, a process by which two sub-threshold stimuli can unite to elicit an
      action potential was shown to be due to conductance changes outlasting the first
      stimulus and summing with the second stimulus-induced conductance changes to
      drive the membrane potential past threshold; (4) anode break excitation, where
      membrane hyperpolarization was shown to produce an action potential by removing
      Na(+) channel inactivation that is present at resting membrane potential. The
      simulations described in this paper provide insights into mechanisms of axonal
      excitation that can be carried out by following an easily understood protocol.

PMID- 10927153
TI  - Homogeneity of kappa statistics in multiple samples.
AB  - The measurement of intra-observer agreement when the data are categorical has
      been the subject of several investigators since Cohen first proposed the kappa
      (kappa) as a chance-corrected coefficient of agreement for nominal scales.
      Subsequent procedures have been developed to assess the agreement of several
      raters using a dichotomous classification scheme, assess majority agreement among
      several raters using a polytomous classification scheme, and the use of kappa as
      an indicator of the quality of a measurement. Further developments include
      inference procedures for testing the homogeneity of k>/=2 independent kappa
      statistics. An executable FORTRAN code for testing the homogeneity of kappa
      statistics (kappa(h)) across multiple sites or studies is given. The FORTRAN
      program listing and/or executable programs are available from the author on
      request.

PMID- 10927156
TI  - Using SAS to calculate the Kent and O'Quigley measure of dependence for Cox
      proportional hazards regression model.
AB  - Kent and O'Quigley (1988) apply the concept of information gain to define a
      measure of dependence (R-squared measure) between explanatory variables and a
      censored response variable within the framework of the Cox model. Two SAS macros
      to calculate this measure are presented. The first one is based on a Newton
      Raphson search and makes use of the SAS IML procedure. The second one is a simple
      grid search using SAS DATA steps and Base-SAS procedures.

PMID- 10927155
TI  - Nuclear-labeling index analysis (NLIA), a software package used to perform
      accurate automation of cell nuclear-labeling index analysis on
      immunohistochemically stained rat liver samples.
AB  - The nuclear labeling index (labeled nuclei/100 nuclei) and the apoptotic index
      (apoptotic cells/100 cells) are important parameters of cell growth and death.
      Automatic counting of labeled nuclei is desirable since manual counting is
      tedious, time-consuming, and with a greater potential for inaccuracies. A nuclear
      labeling index analysis (NLIA) software package was developed in this laboratory
      to perform the counting process automatically and accurately. This software
      package consists of an application program NLIA and a set of macros for obtaining
      nuclear data that is used in Scion Image. It is designed to work cooperatively
      with Scion Image, Adobe Photoshop, and Microsoft Office. NLIA has two basic
      functions: building nuclear data files and analyzing nuclear data. A color image
      captured from an immunohistochemically stained or autoradiographic sample is
      loaded into NLIA. Nuclear data can be entered into the program manually,
      automatically, or in combination. In the manual data entering mode, NLIA acts as
      an object-counting tool, while in the automatic mode it acts as a data picker:
      picking up the data generated by Scion Image into memory. A method to enter
      nuclear data (both labeled nuclei and unlabeled nuclei) in the automatic mode is
      described. The color image is processed in Adobe Photoshop, where the interested
      color ranges are selected and separated. These are then analyzed in Scion Image
      with the help of the macros for obtaining nuclear data. Since the advanced
      particle analysis function is used, the counting process is automatic and rapid.
      Data from thousands of nuclei can be obtained within seconds. To ensure the
      accuracy of the analysis, a nuclear data checking and edit feature is employed in
      NLIA: results of computer-generated counting can be compared with the original
      color image by overlaying the plot of counting results onto the original color
      image. In this way any computer counting mistakes can be easily discovered and
      corrected by the operator. Corrected nuclear data (including nuclear size,
      location, shape) are then stored in data files. These data files can be used in
      NLIA to obtain cell density and nuclear labeling indices. Because criteria for
      obtaining nuclear data (truncation diameter, shape factor) can be set by the
      operator in NLIA, nuclear size distribution and shape variation can be analyzed.
      This method provides a fast and accurate way to determine cell nuclear-labeling
      indices. Currently, Scion Image is a freeware on the internet, and NLIA software
      package is available from our lab home page. Methods presented here expand the
      Scion Image ability to analyze color images by using color separation techniques
      in a commercial graphic application. The instrumentation required can be
      relatively inexpensive, and the methods described may be useful in studies of
      cell kinetics, lesion growth, and tumor therapy.

PMID- 10927157
TI  - MRI characterization of tumors and grading angiogenesis using macromolecular
      contrast media: status report.
AB  - Magnetic resonance imaging (MRI) enhanced with a macromolecular contrast medium
      (MMCM) has been applied successfully to assay tumor microvascular
      characteristics. These MRI-assayed characteristics correlate closely with
      histologic microvascular density, an established surrogate of tumor angiogenesis,
      and with pathologic tumor grade. The utility of MMCM-enhanced MRI for tumor
      characterizations has been established experimentally in a range of cancer types
      including breast, ovary, fibrosarcoma, and prostate. The MMCM-enhanced MRI
      technique can also be applied to monitor changes in tumor vessels that result
      from administration of an angiogenesis inhibitor, antibody against vascular
      endothelial growth factor (VEGF). Suppression of microvascular permeability (up
      to 98%) induced by this inhibitor of angiogenesis was detected and quantified as
      soon as 24 h after initiation of therapy. Thus, MRI assays of tumor microvascular
      characteristics, particularly macromolecular permeability, provide a means to non
      invasively characterize tumors for prognostication, for individualization and
      optimization of treatment, and for monitoring therapeutic response. Pending
      successful completion of drug trials, now in progress, the availability of MMCM
      should permit the immediate application of these powerful techniques in clinical
      practice.

PMID- 10927158
TI  - New approaches for imaging in gene therapy.
AB  - Gene therapy is increasingly used experimentally and clinically to replace
      defective genes and/or impart new functions to cells and tissues. With the recent
      advances in vector design, improvements in transgene and prodrug activation
      strategies, gene therapy has been applied to a wide variety of diseases, tissues
      and organ systems. It is now clear that our specialty will play a critical role
      in gene therapy research and its clinical applications. Three aspects of gene
      therapy are of particular interest to imaging. The first is in delivering genes
      and vector products by minimally invasive interventional techniques. The second
      is in quantitating gene and DNA deliveries, for example, by nuclear imaging.
      Finally, imaging can be used to monitor the levels of transgene expression in
      vivo. A variety of imaging techniques including PET imaging, nuclear imaging, MR
      imaging and optical imaging can potentially be used to achieve the latter. This
      brief introductory overview is intended to summarize current strategies and
      illustrate the role that radiology will play in this field.

PMID- 10927159
TI  - Neuroimaging: do we really need new contrast agents for MRI?
AB  - The use of exogenous contrast media in magnetic resonance imaging of the brain
      has brought dramatic improvement in the sensitivity of detection and delineation
      of pathological structures, such as primary and metastatic brain tumors,
      inflammation and ischemia. Disruption of the blood brain barrier leads to
      accumulation of the intravenously injected contrast material in the extravascular
      space, leading to signal enhancement. Magnetic resonance angiography benefits
      from T(1)-shortening effects of contrast agent, improving small vessel depiction
      and providing vascular visualization even in situations of slow flow. High speed
      dynamic MRI after bolus injection of contrast media allows tracer kinetic
      modeling of cerebral perfusion. Progressive enhancement over serial post-contrast
      imaging allows modeling of vascular permeability and thus quantitative estimation
      of the severity of blood brain barrier disruption. With such an array of
      capabilities and ever improving technical abilities, it seems that the role of
      contrast agents in MR neuroimaging is established and the development of new
      agents may be superfluous. However, new agents are being developed with prolonged
      intravascular residence times, and with in-vivo binding of ever-increasing
      specificity. Intravascular, or blood pool, agents are likely to benefit magnetic
      resonance angiography of the carotid and cerebral vessels; future agents may
      allow the visualization of therapeutic drug delivery, the monitoring of, for
      example, gene expression, and the imaging evaluation of treatment efficacy. So
      while there is a substantial body of work that can be performed with currently
      available contrast agents, especially in conjunction with optimized image
      acquisition strategies, post processing, and mathematical analysis, there are
      still unrealized opportunities for novel contrast agent introduction,
      particularly those exploiting biological specificity. This article reviews the
      current use of contrast media in magnetic resonance neuroimaging, discusses some
      of the developing strategies for new applications of imaging with these agents
      and finally offers some views and indications for contrast agents currently under
      development, as well as some speculation on unsolved problems in neuroimaging,
      and opportunities for novel contrast agents.

PMID- 10927160
TI  - MR contrast media for myocardial viability, microvascular integrity and
      perfusion.
AB  - Cardiovascular imaging requires an appreciation of rapidly evolving MR imaging
      sequences as well as careful utilization of intravascular, extracellular and
      intracellular MR contrast media. At the present time, clinical studies are
      restricted to the use of extracellular MR contrast media. MR imaging has the
      potential to noninvasively measure multiple parameters of the cardiovascular
      system in a single imaging session. Recent advances in fast and ultrafast MR
      imaging have considerably enhanced the capability of this technique, beyond the
      assessment of left ventricular wall motion and morphology into visualization of
      the coronary arteries and measurement of blood flow. During the course of the
      last several years, multiple strategies for imaging viable myocardium have been
      developed and validated using MR contrast media. Contrast enhanced dynamic MR
      imaging provides information regarding microvascular integrity and perfusion.
      Because these information can be provided noninvasively by MR imaging, repeated
      measurements can be performed in longitudinal studies to monitor the progression
      or regression of myocardial injury. Similar studies are needed to examine the
      effects of newly developed cardioprotective therapeutics. Development of suitable
      intravascular MR contrast medium may be essential for visualization of the
      coronary arteries and interventional therapies. MR imaging may emerge as one-stop
      shop for evaluating the heart and coronary system. This capability will make MR
      imaging cost-effective in the first decade of this millennium.

PMID- 10927161
TI  - Contrast-enhanced MRI of the lung.
AB  - The lung has long been neglected by MR imaging. This is due to unique intrinsic
      difficulties: (1) signal loss due to cardiac pulsation and respiration; (2)
      susceptibility artifacts caused by multiple air-tissue interfaces; (3) low proton
      density. There are many MR strategies to overcome these problems. They consist of
      breath-hold imaging, respiratory and cardiac gating procedures, use of short
      repetition and echo times, increase of the relaxivity of existing spins by
      administration of intravenous contrast agents, and enrichment of spin density by
      hyperpolarized noble gases or oxygen. Improvements in scanner performance and
      frequent use of contrast media have increased the interest in MR imaging and MR
      angiography of the lung. They can be used on a routine basis for the following
      indications: characterization of pulmonary nodules, staging of bronchogenic
      carcinoma, in particular assessment of chest wall invasion; evaluation of
      inflammatory activity in interstitial lung disease; acute pulmonary embolism,
      chronic thromboembolic pulmonary hypertension, vascular involvement in malignant
      disease; vascular abnormalities. Future perspectives include perfusion imaging
      using extracellular or intravascular (blood pool) contrast agents and ventilation
      imaging using inhalation of hyperpolarized noble gases, of paramagnetic oxygen or
      of aerosolized contrast agents. These techniques represent new approaches to
      functional lung imaging. The combination of visualization of morphology and
      functional assessment of ventilation and perfusion is unequalled by any other
      technique.

PMID- 10927162
TI  - Contrast-enhanced magnetic resonance imaging of the breast.
AB  - Contrast-enhanced magnetic resonance (MR) imaging is increasingly used as a
      complementary diagnostic modality in breast imaging. The sensitivity of MR
      imaging of the breast for malignancy has consistently been reported to be
      excellent. The specificity has been rather variable. Study methods and imaging
      techniques are not standardized and there is still a great deal of uncertainty
      about MR imaging's place in clinical practice. Nevertheless, radiologists should
      be familiar with the current technique and the varying MR appearance of breast
      tumors to improve the accuracy of this method. This paper reviews the techniques
      for breast MR imaging, the pathopysiologic basis of contrast enhancement in
      breast tumors, and the current knowledge about detection and differentiation of
      breast tumors. In addition, future directions for breast MR imaging are
      discussed.

PMID- 10927163
TI  - MRI of the female and male pelvis: current and future applications of contrast
      enhancement.
AB  - Magnetic resonance imaging (MRI) of the pelvis has proven to be a most valuable
      diagnostic tool to examine pathologies of various organ systems in the pelvis.
      For most conditions MRI was found to be superior to other imaging modalities,
      like ultrasound and computed tomography. Controversy still exists on the value of
      intraluminal and intravenous contrast enhancement. This article gives an overview
      on currently available intraluminal and intravenous contrast agents. The
      techniques and results for contrast-enhanced MRI in the female and male pelvis
      are discussed based on a review of the literature. New developments and upcoming
      techniques, such as lymph node specific contrast agents and breathhold volumetric
      MRI, are described and initial results are presented.

PMID- 10927164
TI  - Bone and soft tissue tumors: the role of contrast agents for MR imaging.
AB  - Magnetic resonance imaging is an important modality for the imaging evaluation of
      musculoskeletal tumors. Although there is general agreement on the value of
      unenhanced MR in detection, diagnosis and staging, intravenous use of gadolinium
      contrast media (gd-CM) is indicated in selected cases. The purpose of this
      article is to review the basic pharmacokinetic principles and imaging techniques
      for static and dynamic contrast-enhanced MR imaging and to highlight the most
      important indications for administration of gd-CM in patients with
      musculsokeletal tumors and tumor-like lesions: adding specificity in tissue
      characterization, staging of local extent and biopsy planning, monitoring
      preoperative chemotherapy and detection of recurrence.

PMID- 10927165
TI  - MR-angiography: the role of contrast agents.
AB  - Contrast-enhanced 3D MR angiography (MRA) permits comprehensive assessment of the
      supraaortic arteries as well as the arterial system in the chest, abdomen and
      lower extremities. 3D MRA combines intravenous injection of a non-nephrotoxic,
      paramagnetic, extracellular contrast agent that increases the signal intensity of
      blood by shortening its T1 value with the acquisition of a fast 3D data set. High
      contrast between the vascular lumen and surrounding tissues, inherent three
      dimensionality and the ability to collect image data in the chest and abdomen
      under apnea conditions all contribute to excellent image quality. This review
      provides clinical applications of 3D MRA in the chest, abdomen and lower
      extremities based upon the available literature and several clinical examples.

PMID- 10927166
TI  - Iron oxide-enhanced MR lymphography: initial experience.
AB  - The detection of nodal metastases is of utmost importance in oncologic imaging.
      Ultrasmall superparamagnetic iron oxide particles (USPIO) are novel contrast
      agents specifically developed for MR lymphography. After intravenous
      administration, they are taken up by the macrophages of the lymph nodes, where
      they accumulate. They reduce the signal intensity (SI) of normally functioning
      nodes on postcontrast T2-and T2*-weighted images through the magnetic
      susceptibility effects on iron oxide. Metastatic nodes, in which macrophages are
      replaced by tumor cells, show no significant change in SI on postcontrast T2-and
      T2*-weighted images. Early clinical experience suggests that USPIO-enhanced MR
      lymphography improves the sensitivity and specificity for the detection of nodal
      metastases. It also suggests that micrometastases could be detected in normal
      sized nodes. This article reviews the physiochemical properties of USPIO contrast
      agents, their enhancement patterns, and early clinical experience.

PMID- 10927167
TI  - Forum on therapeutic applications of reactive oxygen and nitrogen species in
      human disease.

PMID- 10927168
TI  - Interaction of peroxynitrite with selenoproteins and glutathione peroxidase
      mimics.
AB  - Peroxynitrite is an oxidant generated under inflammatory conditions, acting in
      defense against invading microorganisms. There is a need for protection of the
      organism from damage inflicted by peroxynitrite. Selenium-containing compounds,
      notably ebselen, have a high second-order reaction rate constant (approx. 2 x
      10(6) M(-1) s(-1)), which makes them candidates for efficient protection. This
      applies also for selenium in proteins, occurring as selenocysteine or
      selenomethionine residues. Glutathione peroxidases, thioredoxin reductase, and
      selenoprotein P have been shown to play a potential role in protection against
      peroxynitrite. Tellurium-containing compounds also react with peroxynitrite.

PMID- 10927169
TI  - Reactive oxygen species, cell signaling, and cell injury.
AB  - Oxidative stress has traditionally been viewed as a stochastic process of cell
      damage resulting from aerobic metabolism, and antioxidants have been viewed
      simply as free radical scavengers. Only recently has it been recognized that
      reactive oxygen species (ROS) are widely used as second messengers to propagate
      proinflammatory or growth-stimulatory signals. With this knowledge has come the
      corollary realization that oxidative stress and chronic inflammation are related,
      perhaps inseparable phenomena. New pharmacological strategies aimed at
      supplementing antioxidant defense systems while antagonizing redox-sensitive
      signal transduction may allow improved clinical management of chronic
      inflammatory or degenerative conditions, including Alzheimer's disease.
      Introduction of antioxidant therapies into mainstream medicine is possible and
      promising, but will require significant advances in basic cell biology,
      pharmacology, and clinical bioanalysis.

PMID- 10927170
TI  - Diazeniumdiolates: pro- and antioxidant applications of the "NONOates".
AB  - Diazeniumdiolates are compounds containing the X-[N(O)NO](-) structural unit that
      as a class offer many advantages as tools for probing the roles of nitric oxide
      (NO) in biological redox processes. Available examples in which X is a secondary
      amine group spontaneously generate up to two molecules of NO per [N(O)NO](-) unit
      when dissolved in aqueous media; their half-lives range from 2 s (for X = L
      prolyl) to 20 h [for X = (H(2)NCH(2)CH(2))(2)N] at pH 7. 4 and 37 degrees C, and
      are in general relatively little influenced by medium effects or metabolism. When
      X = O(-) (Angeli's salt), first-order dissociation produces NO(-) rather than NO,
      but the ion becomes an NO source on 1-electron oxidation; diazeniumdiolate
      derived NO can also be used to generate reactive nitrogen/oxygen species with
      higher nitrogen oxidation states (+3 and +4) in the presence of selected
      oxidizing agents. The advantages of diazeniumdiolates in biomedical research are
      briefly illustrated with examples from the recent literature probing NO's role in
      inhibiting oxidative drug metabolism, radical-induced lipid oxidation, the
      cytotoxicity of reactive oxygen species, and ischemia-induced vascular
      reoxygenation injury. Future work with this compound class should provide further
      insight into the mechanisms of NO's involvement in pro- and antioxidant
      processes, and may well lead to important medicinal advances, including reversal
      of cerebral vasospasm and radiosensitization of hypoxic tumors.

PMID- 10927171
TI  - Discovery and development of neuronal nitric oxide synthase inhibitors.
AB  - The role of neuronally derived nitric oxide (NO) in neurotransmission and neural
      injury remains an area of active investigation. NO generation has been postulated
      to be involved in the deleterious events surrounding ischemia/reperfusion injury
      either directly or via the production of more reactive oxidants such as
      peroxynitrite. In our search for novel therapeutics for the treatment of a
      variety of neurological diseases including stroke, we have discovered novel,
      potent, and selective inhibitors of the neuronal nitric oxide synthase (nNOS)
      isoform. These compounds have proven to be effective in models of
      ischemia/reperfusion supporting the role of nNOS in these processes. The effects
      of these compounds as well as additional aspects critical to their development
      will be presented.

PMID- 10927172
TI  - Biological chemistry and clinical potential of S-nitrosothiols.
AB  - S-Nitrosothiols are endogenous metabolites of nitric oxide that have been
      detected in extra- and intracellular spaces. Many biological functions of S
      nitrosothiols have been described that can be categorized as being due to one or
      more of the following: (i) nitric oxide release, (ii) transnitrosation, (iii) S
      thiolation, and (iv) direct action. This emphasizes the fact that S-nitrosothiols
      are more than simply nitric oxide donors. Many of the biological functions that
      have been described for S-nitrosothiols have clinical correlates. This review
      describes the biological chemistry, biological actions, and clinical potential of
      these compounds.

PMID- 10927173
TI  - Peroxynitrite scavenging by metalloporphyrins and thiolates.
AB  - The rate constant for the reaction of nitric oxide with superoxide virtually
      assures that peroxynitrite will be formed to some extent in any cell or tissue
      where both radicals exist simultaneously. The precise biological targets for
      peroxynitrite and the nature of the modification of those targets vary
      dramatically depending on their relative concentrations and the rates and
      duration of peroxynitrite formation. Thus, peroxynitrite may have physiological
      functions in addition to pathological ones. Peroxynitrite scavenger compounds may
      prove to be therapeutic by effectively intercepting higher levels of
      peroxynitrite and thereby preventing injurious oxidative modifications of
      cellular components. Thiols and thiolates comprise a class of sacrificial
      scavengers that react with peroxynitrite anion with rate constants ranging from 2
      x 10(3) M(-1) s(-1) to 2 x 10(8) M(-1) s(-1), depending on the microenvironment
      of the thiol. Several Mn and Fe porphyrins have been shown to react quite rapidly
      with peroxynitrite (10(6) to 10(7) M(-1) s(-1)) and decompose it in a catalytic
      manner; Mn porphyrins require exogenous reductants for complete cycling whereas
      Fe porphyrins do not. Sacrificial thiol/thiolate scavengers effectively quench
      the total oxidative yield of peroxynitrite, whereas the catalytic porphyrins
      redirect it and can, under some conditions, enhance total nitration and oxidative
      yield.

PMID- 10927174
TI  - Nitric oxide (NO)-related pharmaceuticals: contemporary approaches to therapeutic
      NO modulation.
AB  - The biologically important gaseous radical, nitric oxide (NO), is a versatile
      chemical entity that enters into regulatory, protective, and adverse interactions
      with biomolecules and cells, in some cases through NO-derived nitrogen oxide
      species. Both excess tissue NO and its insufficiency have been implicated in the
      genesis or evolution of several important disease states. The associated medical
      needs and commercial opportunities have fostered attempts to modulate tissue NO
      tone for symptomatic benefit or therapeutic gain. State-of-the-art strategies for
      NO modulation in contemporary drug discovery and development encompass sexual
      dysfunction, cardiovascular, and antiinflammatory indications. Increased
      understanding of NO's physiological chemistry and ways to target its pharmacology
      appear critical to the successful clinical exploitation of NO's diverse
      properties. Integration of research on both the basic science of NO's mechanistic
      biology and the applied science of drug discovery and development represents a
      millennium mandate to the pharmaceutical industry in the area of NO-related
      therapeutics.

PMID- 10927175
TI  - Pyridoxalated hemoglobin polyoxyethylene: a nitric oxide scavenger with
      antioxidant activity for the treatment of nitric oxide-induced shock.
AB  - Hemoglobins modified for therapeutic use as either hemoglobin-based oxygen
      carriers or scavengers of nitric oxide are currently being evaluated in clinical
      trials. One such product, pyridoxalated hemoglobin polyoxyethylene conjugate
      (PHP), is a human-derived and chemically modified hemoglobin that has yielded
      promising results in Phase II clinical trials, and is entering a pivotal Phase
      III clinical trial for the treatment of shock associated with systemic
      inflammatory response syndrome (SIRS). Shock associated with SIRS is a NO-induced
      shock. PHP, a new mechanism-based therapy, has been demonstrated in clinical
      trials to have the expected hemodynamic activity of raising blood pressure and
      reducing catecholamine use, consistent with its mechanism of action as a NO
      scavenger. PHP is conjugated with polyoxyethylene, which results in a surface
      decorated molecule with enhanced circulation time and stability as well as in
      attachment of soluble red blood cell enzymes, including catalase and superoxide
      dismutase. PHP thus contains an antioxidant profile similar to the intact red
      blood cell and is therefore resistant to both initial oxidative modification by
      oxidants such as hydrogen peroxide and subsequent ferrylhemoglobin formation.
      These studies suggest both that the redox activity of modified hemoglobins can be
      attenuated and that modified hemoglobins containing endogenous antioxidants, such
      as PHP, may have reduced pro-oxidant potential. These antioxidant properties, in
      addition to the NO-scavenging properties, may allow the use of PHP in other
      indications in which excess NO, superoxide, or hydrogen peroxide is involved,
      including ischemia-reperfusion injury and hemorrhagic shock.

PMID- 10927176
TI  - Biochemical aspects of the reaction of hemoglobin and NO: implications for Hb
      based blood substitutes.
AB  - The role of Hemoglobin (Hb) on nitric oxide (NO) biology has received much
      attention. Until recently, the reaction between erythrocytic Hb and NO was
      generally considered in the context of mechanisms that safely detoxify NO.
      However, recent insights suggest that properties associated with the red blood
      cell limit NO-Hb interactions under physiological conditions, and provide some
      resolution to the question of how NO functions in the presence of blood.
      Furthermore, Hb-dependent mechanisms that preserve, not destroy NO bioactivity in
      vivo have also been proposed. The emerging picture suggests that the interplay
      between NO and erythrocytic Hb is important in regulating the functions of both
      these molecules in vivo. However, Hb-dependent scavenging and loss of NO function
      is significant when this heme protein is present outside the red blood cell. This
      can occur during hemolysis or administration of Hb-based blood substitutes.
      Scavenging of NO is a significant problem that limits the use of Hb-based blood
      substitutes in the clinic, and development of Hb molecules that do not
      efficiently react with NO remains an important area of investigation. In this
      article, the reactions between NO and erythrocytic Hb or cell-free Hb are
      described and the effects on NO and Hb function in vivo and development of blood
      substitutes discussed.

PMID- 10927177
TI  - Cerebral ischemia: gene activation, neuronal injury, and the protective role of
      antioxidants.
AB  - A large number of gene products appear after an ischemic insult making it
      difficult to decipher which genes are involved in tissue injury. Reactive oxygen
      species (ROS) can influence gene expression and have a role in the events that
      lead to neuronal death. In global cerebral ischemia the oxidative responsive
      transcription factor, NF-kappa B, is persistently activated in neurons that are
      destined to die. There are several potential routes through which NF-kappa B can
      act to induce neuronal death, including production of death proteins and an
      aborted attempt to reenter the cell cycle. NF-kappa B is only transiently
      activated in neurons that survive. Persistent NF-kappa B activation can be
      blocked by antioxidants, which suggests that the neuroprotective effect of
      antioxidants may be due to inhibiting activation of NF-kappa B.

PMID- 10927178
TI  - Dithiocarbamates: effects on lipid hydroperoxides and vascular inflammatory gene
      expression.
AB  - Dithiocarbamates are a well-defined family of antioxidants that may have
      therapeutic uses such as in treatment of inflammation and atherosclerosis. A
      critical event in the pathogenesis of atherosclerosis is the infiltration of
      inflammatory cells into the vessel wall. Vascular cell adhesion molecule-1 (VCAM
      1) plays a pivotal role in this process by mediating leukocyte binding to
      endothelial cells. VCAM-1 expression is stimulated by oxidized polyunsaturated
      fatty acids such as 13-hydroperoxy-octadecadienoic acid (13-HPODE), and this
      lipid hydroperoxide has been proposed to be a second messenger for induction of
      VCAM-1 gene expression. Pyrrolidine dithiocarbamate (PDTC) markedly represses
      cytokine-induced VCAM-1 gene expression in cultured human endothelial cells;
      however, its effects on the oxidative second messenger pathway are unknown. Using
      a lipoxygenase (LO) inhibition assay in tandem with a colorimetric assay for
      lipid peroxides, we determined that PDTC does not inhibit the enzymatic oxidation
      of linoleic acid to 13-HPODE by LO, but directly interacts with and chemically
      reduces 13-HPODE. We hypothesize that dithiocarbamates may intercept the
      oxidative second-messenger-induced expression of VCAM-1 and other redox-regulated
      genes important in inflammation and atherosclerosis.

PMID- 10927179
TI  - Phenolic antioxidants: a rationale for design and evaluation of novel antioxidant
      drug for atherosclerosis.
AB  - With increasing evidence that shows the involvement of active oxygen and nitrogen
      species in a variety of disorders, cancer, and aging, the role of antioxidant
      against oxidative stress has received renewed attention. In this review article,
      a rationale for design of lipophilic, radical-scavenging antioxidant is presented
      and the potency of a novel antioxidant, 2,3-dihydro-5-hydroxy-2,2-dipentyl-4, 6
      di-tert-butylbenzofuran (BO-653), as an inhibitor of LDL oxidation was evaluated
      by considering various factors such as reactivity toward radicals, localization,
      and mobility in the lipoprotein, and fate of its radical. The anti-atherogenic
      activity of BO-653 was compared with those of alpha-tocopherol, probucol, and its
      metabolites. Furthermore, a novel function of phenolic antioxidants such as cell
      regulation and induction of phase II defense antioxidants are also discussed.

PMID- 10927180
TI  - Mitochondrially targeted antioxidants and thiol reagents.
AB  - Mitochondrial oxidative damage and dysfunction contributes to a number of cell
      pathologies. To investigate how this damage affects cell function we have
      developed mitochondrially targeted antioxidants and thiol reagents by covalently
      linking them to lipophilic cations. The cation drives the selective accumulation
      of these reagents into mitochondria within cells where the antioxidants decrease
      oxidative damage and the thiol reagents enable measurement of the redox status of
      thiol proteins. In conjunction with cell and animal models of apoptosis,
      oxidative damage, and nitric oxide signaling, these molecules may provide new
      insights into the roles of mitochondria in human pathologies.

PMID- 10927181
TI  - Reactions of pholasin with peroxidases and hypochlorous acid.
AB  - The ability of myeloperoxidase (MPO) and horseradish peroxidase (HRP) to induce
      chemiluminescence (CL) in Pholasin (Knight Scientific, Plymouth, UK), the
      photoprotein of the Common Piddock Pholas dactylus, was studied. The oxidation of
      Pholasin by compound I or II of HRP induced an intense light emission, whereas
      native HRP showed only a small effect. The luminescence observed upon incubation
      of Pholasin with native MPO was diminished by preincubation with catalase.
      Considering the high instability of diluted MPO, it is concluded that traces of
      hydrogen peroxide in water converted MPO to its active forms, compound I and/or
      II, which are able to oxidize Pholasin. Indeed, the addition of hydrogen peroxide
      to a mixture of MPO and Pholasin induced an intense burst of light. This emission
      was enhanced in degree and duration in the absence of chloride. Hypochlorous
      acid, the reaction product of Cl(-) and compound I of MPO, was itself able to
      elicit a luminescent response in Pholasin and this luminescence was strongly
      inhibited by methionine and taurine. However, both of these HOCl scavengers only
      slightly reduced the light emission induced by MPO/H(2)O(2) in both the presence
      or absence of chloride. Thus, hypochlorous acid produced by the MPO/H(2)O(2)/Cl(
      ) system, under the conditions described in this study, did not contribute to
      Pholasin luminescence. The Pholasin luminescence elicited by formyl-leucyl
      methionyl-phenylalanine (fMLP)-stimulated neutrophils depends both on superoxide
      anion radicals and higher oxidation states of myeloperoxidase (but not on
      hypochlorous acid). This is shown by the inhibition of luminescence with
      superoxide dismutase and potassium cyanide, together with the lack of effect of
      both methionine and taurine. The luminescence response is about eight times
      greater in cells stimulated with fMLP/cytochalasin B than with fMLP alone.

PMID- 10927182
TI  - Carnosine reacts with a glycated protein.
AB  - Oxidation and glycation induce formation of carbonyl (CO) groups in proteins, a
      characteristic of cellular aging. The dipeptide carnosine (beta-alanyl-L
      histidine) is often found in long-lived mammalian tissues at relatively high
      concentrations (up to 20 mM). Previous studies show that carnosine reacts with
      low-molecular-weight aldehydes and ketones. We examine here the ability of
      carnosine to react with ovalbumin CO groups generated by treatment of the protein
      with methylglyoxal (MG). Incubation of MG-treated protein with carnosine
      accelerated a slow decline in CO groups as measured by dinitrophenylhydrazine
      reactivity. Incubation of [(14)C]-carnosine with MG-treated ovalbumin resulted in
      a radiolabeled precipitate on addition of trichloroacetic acid (TCA); this was
      not observed with control, untreated protein. The presence of lysine or N-(alpha)
      acetylglycyl-lysine methyl ester caused a decrease in the TCA-precipitable
      radiolabel. Carnosine also inhibited cross-linking of the MG-treated ovalbumin to
      lysine and normal, untreated alpha-crystallin. We conclude that carnosine can
      react with protein CO groups (termed "carnosinylation") and thereby modulate
      their deleterious interaction with other polypeptides. It is proposed that,
      should similar reactions occur intracellularly, then carnosine's known "anti
      aging" actions might, at least partially, be explained by the dipeptide
      facilitating the inactivation/removal of deleterious proteins bearing carbonyl
      groups.

PMID- 10927184
TI  - Preface.

PMID- 10927183
TI  - Overexpression of copper/zinc superoxide dismutase does not prevent neonatal
      lethality in mutant mice that lack manganese superoxide dismutase.
AB  - There are two types of intracellular superoxide dismutases: the mitochondrial
      manganese SOD (MnSOD) and the cytoplasmic copper/zinc SOD (CuZnSOD). Mutant mice
      that lack MnSOD die shortly after birth because of cardiomyopathy and
      mitochondrial injury. In order to verify if CuZnSOD could compensate for MnSOD
      deficiency, a new mutant mouse that overexpresses CuZnSOD but is deficient in
      MnSOD was generated by crossing MnSOD knockout mice with CuZnSOD transgenic mice.
      CuZnSOD activity was significantly increased in the blood, brain, liver, and
      heart of MnSOD knockout, CuZnSOD transgenic mice when compared with nontransgenic
      mice. However, overexpression of CuZnSOD did not prevent neonatal lethality in
      mice that lack MnSOD, nor did it prevent oxidative aconitase inactivation, nor
      did it rescue MnSOD-deficient astrocytes in culture. Based on our findings, which
      emphasize the strong enzymatic compartmentalization of CuZnSOD and MnSOD,
      therapeutic antioxidant strategies should consider the final intracellular
      localization of the antioxidant used, especially when those strategies are
      directed against mitochondrial diseases.

PMID- 10927185
TI  - Detection and a possible mechanism of magnetic field effect on the crystal growth
      of sedimentary calcium carbonate.
AB  - Sedimentary calcium carbonate was grown at a physiological pH6.8 from a mixture
      of equivolume of 70 mM Ca(NO(3))(2) and 70 mM NaHCO(3) aqueous solution. The
      kinetics of the crystal growth was monitored by means of turbidity measurement.
      The apparent absorption is gradually increased with the elapsed time after the
      mixing and reaches its maximum at t(max). The average t(max) is significantly
      decreased from <t(max)>=467 s (for n=13 runs) to 408 s (n=13) by application of
      the static magnetic field (SMF) of H=400 mT to the precipitating solution. The
      application of SMF at 120 s later the mixing shows the same <t(max)>=396 s (n=9)
      as that of 408 s. It has been thus detected that the application of SMF is
      ineffective in the stage of the nucleation or the earlier stage of the crystal
      growth but effective in the Ostwald ripening stage of the growth nucleus or the
      later stage of the crystal growth where large numbers of the growing crystalline
      particles seem greater than a few hundred nanometers. A possible mechanism for
      the SMF effect is as follows. An ion escaping from the growing crystal surface
      with a certain 'migration velocity' due to a random walk process has significant
      probability to drift onto the identical surface or at least the identical crystal
      by means of Lorentz force, because the translational displacement of the crystal
      during a cycle of the cyclotron motion of the ion is smaller than the size of the
      growing crystal. This type of drift results in the suppression of re-dissolution
      of the ions on the growing surface and in the acceleration of the growth in the
      later stage of the crystal growth. The undetected SMF effect in the earlier stage
      of the crystal growth can be partly attributed to the re-dissolution due to the
      thermodynamic instability of the small nuclei which predominates over the
      presumable SMF effect. This can be partly ascribed to the large translational
      displacement of the small particle. The application of this mechanism to an
      oscillating magnetic field will predict the presence of a window for the
      frequency of the oscillating magnetic field.

PMID- 10927186
TI  - An idea for a relation between the frequency and intensity of the optimal
      oscillating magnetic field for the magnetic effects.
AB  - An idea for a relation between the frequency and intensity of the optimal
      oscillating magnetic field for the magnetic effects has been presented. An
      estimated optimal frequency is about 150 Hz for a system containing ions of
      effective molecular weight of M approximately 100 under a square pulsing magnetic
      field of intensity H=1 mT.

PMID- 10927187
TI  - Effects of static magnetic field on dissolved oxygen levels in aqueous solutions
      containing copper(II), iron(II), and heme iron(III) complexes.
AB  - Trace metal ions like copper and iron play important roles such as binding,
      transport, and storage of molecular dioxygen in a wide variety of living systems.
      The effects of static magnetic fields on the dissolved oxygen (DO) levels in
      aqueous solutions containing copper(II), iron(II), and their bioligand complexes
      were investigated. The DO levels in aqueous solutions containing the stable
      copper(II) complexes such as Cu(II)-Arg, His, GGH and BSA systems increased when
      the applied magnetic field increased. However, the magnetic field-dependent
      changes of DO levels were not observed by the unstable Cu(II) complexes such as
      Cu(II)-Lys, Gly, Gly-His and Hb systems. Especially, DO levels in aqueous
      solutions containing Cu(II)-His or BSA complexes increased 1.1-fold to those of
      the control levels at 200 mT of the applied magnetic field. In contrast, DO
      levels in aqueous solutions containing iron(II) decreased significantly when the
      magnetic field increased, which in turn promoted the Fe(II)-induced
      lipidperoxidation in liposomes. DO levels in aqueous solutions containing Fe(II)
      His complex decreased 0.9-fold to those of the control levels at 200 mT of the
      magnetic field for 30 min. While, the magnetic field-dependent changes of DO
      levels increased significantly in aqueous solutions containing heme iron(III)
      complexes, suggesting that heme iron(III) is reduced to heme iron(II) under
      exposure of the magnetic field and thus the incorporation of molecular dioxygen
      in aqueous solutions is enhanced. These results indicate that the effect of the
      magnetic fields on DO levels in aqueous solutions must be discussed in terms of a
      concept: formation of intermediate complexes consisting of molecular dioxygen
      copper or iron and bioligands under physiological conditions and the following
      enhancement of incorporation of molecular dioxygen by the complexes, that in turn
      activate the molecular dioxygen.

PMID- 10927188
TI  - The magnetic field effect affecting on the metallic chemical components of egg
      shell as demonstrated for breeding chicken.
AB  - The chickens were raised under fixation of the permanent magnet (80 mT) and the
      effect of extra magnetic field, which affects on the content of the several
      inorganic chemical elements of egg shell, was investigated by X-ray fluorescence
      spectroscopy. From 3 days after fixing the magnet, the relative concentration of
      Ca begun to increase. After 10 days, the relative contents of Ca were decreased,
      while conversely the contents of K were increased. Though there was a linear
      relationship between Ca content and P content in inner layer of chicken egg
      shell, the relationship was greatly hindered by applying the static magnetic
      field. The experimental result suggests that both Ca and K ion transport can be
      perturbed by addition of extra magnetic field in the incubation processes of
      chicken egg, and that Ca, P and K ions play the important role in egg shell
      formation.

PMID- 10927189
TI  - Age and magnetic effects on ectopic bone formation induced by purified bone
      morphogenetic protein.
AB  - A mixture of heparin-Sepharose-purified bovine bone morphogenetic protein (BMP)
      and type I atellocollagen was implanted in the subcutaneous tissues of 4-week, 10
      month and 18-month-old rats. The implants were removed at 7, 14 and 21 days after
      implantation. The effects of rat age on ectopic bone formation were evaluated on
      the explants using H&E staining, morphometric analysis, alkaline phosphatase
      (ALP) activity and calcium (Ca) content determination, as well as
      immunohistochemical staining of type IV collagen present in the basement membrane
      of blood vessels. On day 14 and 21, bone was observed in 4-week and 10-month-old
      rats but the amount of bone formed in the later was less than in the former. In
      18-month-old rats, bone was first found focally in very limited regions of the
      explants on day 21 and the amount of bone was much less than in 4-week-old rats.
      At all periods ALP activity was higher in younger rats. On day 7, there were more
      blood vessels in the explants of 4-week-old rats than in those of 10- or 18-month
      old rats. On day 14 and 21, more blood vessels were found in the central regions
      of the explants in 4-week-old rats than in the same regions in 10- or 18-month
      old rats. The findings in the present study indicated that the rate and quantity
      of ectopic bone formation were reduced, and that the difference in blood vessel
      distribution might be related to the reduction in ectopic bone formation in aged
      rats, and suggest that the difference in blood vessel distribution is related to
      ectopic bone formation. Magnetism can stimulate ectopic bone formation induced by
      BMP.

PMID- 10927190
TI  - Effects of an in vivo 60 Hz magnetic field on monoamine levels in mouse brain.
AB  - We studied the effects of electromagnetic fields (EMF) on mouse brain monoamine
      levels in models of (1) chronic exposure (7 days) of EMF (60 Hz, 10 Gauss) to
      mice in a vertical orientation, (2) prolonged chronic exposure (84 days) of EMF
      (60 Hz, 10 Gauss) to mice in a horizontal mode, (3) acute exposure (6 h) of EMF
      (60 Hz, 10 Gauss) to senescence accelerated mice (SAM-P8) at ages 1, 3, 6, 9 and
      12 months in the horizontal mode, and (4) acute exposure (1 h) of EMF (60 Hz, 1,
      3.3 and 10 Gauss) to restrained mice in the horizontal mode. No model except the
      restrained one changed their monoamine or metabolite levels by exposure to EMF.
      In the restrained group, dihydroxyphenylacetic acid (DOPAC) was significantly
      increased in the hippocampus (HP) and hypothalamus (HY), homovanillic acid (HVA)
      was significantly increased in HY, and 5-hydroxyindolacetic acid (5-HIAA) was
      significantly increased in HP and thalamus-midbrain (TM). None of these monoamine
      metabolite levels were changed when the mouse was restrained without EMF
      exposure. These results suggest that monoamine metabolism is influenced by EMF
      only when the exposure is in the same direction as the mouse position. Another
      possibility is that EMF enhances the restraint stress since stress is known to
      increase monoamine metabolism.

PMID- 10927191
TI  - Alternate magnetic fields potentiate monoamine oxidase activity in the brain.
AB  - Catecholamines and serotonin, which act as neurotransmitters and regulate blood
      circulation, are degraded by monoamine oxidase (MAO) [EC 1.4.3.4.] which exists
      two iso-enzymes named MAO-A and MAO-B. In this study, the effects of magnetic
      fields on MAO activity in the rat brain were examined. MAO-A activity was not
      changed in static magnetic fields (0.1-340 mT) or in 10-500 mT/s of alternate
      isosceles triangular magnetic fields (AITMF) (50 Hz). MAO-B activity was not
      changed in static magnetic fields (0.1-340 mT) and in 10, 34, 340, 95, 105, 110,
      and 340 mT/s of AITMF. However, it was increased to 114% in the 100 mT/s of
      AITMF. In 100 mT/s, Michaelis constant (K(m)) significantly decreased to 72%,
      suggesting that the affinity of the substrate to the enzyme also increased. These
      results indicate that only MAO-B was influenced by AITMF with 'active window'
      phenomenon, and suggest that AITMF might affect neural activity and hemodynamics
      by altering MAO-B.

PMID- 10927192
TI  - Pulsed magnetic fields enhance nitric oxide synthase activity in rat cerebellum.
AB  - The effect of pulsed magnetic fields on nitric oxide synthase (NOS) activity in
      the rat brain was investigated. Sprague-Dawley rats (male, 200-250 g body weight)
      brain were dissected regionally, and the crude enzyme solutions were treated with
      pulsed DC, AC or static DC magnetic fields at 0 degrees C for 1 h. After
      exposure, NOS activity was measured as nitrite and nitrate levels generated from
      incubation with arginine, CaCl(2) and beta-nicotinamide adenine dinucleotide
      phosphate. Under these experimental conditions, neither AC nor static DC field
      treatment showed any significant change in NOS activity. A significant increase
      in NOS activity was observed in the cerebellum (111.2+/-2.0%, P<0.05, five
      separate experiments) for a 1 Gauss (0.1 mT) pulsed DC field. Under the same
      experimental condition, only a slight change or no effect was observed in the
      hippocampus, cortex, medulla oblongata, hypothalamus, striatum and midbrain.
      These studies suggest that pulsed magnetic fields result in a different effect on
      NOS activity in the cerebellum of the rats.

PMID- 10927194
TI  - Magnetic fields and lipoic acid influence the respiratory burst in activated rat
      peritoneal neutrophils.
AB  - When rat (Sprague-Dawley, male) peritoneal neutrophils are exposed to 60 Hz, 1
      Gauss, magnetic fields and activated by phorbor 12-myristate 13-acetate they
      undergo an enhanced respiratory burst (S. Roy, Y. Noda, V. Eckert, M.G. Traber,
      A. Mori, R.P. Liburdy, L. Packer, The phorbol 12-myristate 13-acetate (PMA)
      induced oxidative burst in rat peritoneal neutrophils is increased by a 0. 1 mT
      (60 Hz) magnetic field, FEBS Lett. 376 (1996) 164-6). In the present study, the
      reproducibility of these previous findings was confirmed using a new dual
      monochrometer exposure system; a 1 Gauss, 60 Hz magnetic field enhanced the
      production of fluorescence during the respiratory burst. Dose-response studies
      employed static DC magnetic fields of up to 20 Gauss. Both static DC fields (2.5
      and 20 Gauss) showed enhancement of fluorescence production during the
      respiratory burst. Pre-treatment of neutrophil cells for 10 min at 37 degrees C
      with an antioxidant, lipoic acid (1-100 uM), significantly elevates fluorescence
      production in a dose-response manner. The combination of lipoic acid pre
      treatment and DC field (2.5 Gauss) exposure further enhanced fluorescence.

PMID- 10927193
TI  - Enhancement of nitric oxide generation by low frequency electromagnetic field.
AB  - Oxidative stress is implicated in the intracellular signal transduction pathways
      for nitric oxide synthase (NOS) induction. The electromagnetic field (EMF) is
      believed to increase the free radical lifespan [S. Roy, Y. Noda, V. Eckert, M.G.
      Traber, A. Mori, R. Liburdy, L. Packer, The phorbol 12-myristate 13-acetate (PMA)
      induced oxidative burst in rat peritoneal neutrophils is increased by a 0.1 mT
      (60 Hz) magnetic field, FEBS Lett. 376 (1995) 164-6; F.S. Prato, M. Kavaliers,
      J.J. Carson, Behavioural evidence that magnetic field effects in the land snail,
      Cepaea nemoralis, might not depend on magnetite or induced electric currents,
      Bioelectromagnetics 17 (1996) 123-30; A.L. Hulbert, J. Metcalfe, R. Hesketh,
      Biological response to electromagnetic fields, FASEB 12 (1998) 395-420]. We
      tested the effects of EMF on endotoxin induced nitric oxide (NO) generation in
      vivo. Male BALB/C mice were injected with lipopolysaccharide (LPS)
      intraperitoneously (i.p.), followed by the exposure to EMF (0.1 mT, 60 Hz). Five
      hours and 30 min after the LPS administration, mice were administered with a NO
      spin trap, ferrous N-methyl-D-glucaminedithiocarbamate (MGD-Fe). Thirty minutes
      later, mice were sacrificed, and their livers were removed. The results were
      compared to three control groups: group A (LPS (-) EMF(-)); group B (LPS(-)
      EMF(+)); group C (LPS(+) EMF(-)). The ESR spectra of obtained livers were
      examined at room temperature. Three-line spectra of NO adducts were observed in
      the livers of all groups. In groups A and B very weak signals were observed, but
      in groups C and D strong spectra were observed. The signal intensity of the NO
      adducts in Group D was also significantly stronger than that in Group C. EMF
      itself did not induce NO generation, however, it enhanced LPS induced NO
      generation in vivo.

PMID- 10927195
TI  - Effect of static magnetic fields on bacteria: Streptococcus mutans,
      Staphylococcus aureus, and Escherichia coli.
AB  - Biological effect of static magnetic field was investigated by using ferrite
      magnets to conduct a magnetic field exposure experiment on three species of
      bacteria: Streptococcus mutans, Staphylococcus aureus, and Escherichia coli. The
      effects were evaluated by culturing the bacteria and determining their growth
      rate, the maximum numbers of bacteria, and [3H]-thymidine incorporation. The
      results showed that the ferrite magnet caused strength-dependent decreases in the
      growth rate and growth maximum number of bacteria for S. mutans and S. aureus
      when cultured under anaerobic conditions, but that their growth was not inhibited
      under aerobic conditions. In addition, [3H]-thymidine was added after culturing
      each of the species of bacteria for 18 h. After that, culture was continued until
      24 h, and changes in [3H]-thymidine incorporation were investigated. But no
      effect of the magnetic fields was detected. These findings suggested that oxygen
      related to growth the cases of S. mutans, S. aureus. However, no growth effects
      were detected on E. coli cultures.

PMID- 10927196
TI  - Effects of a magnetic fields on the various functions of subcellular organelles
      and cells.
AB  - Magnetic fields (MF) are widely distributed in environment and their effects are
      increasing by the development of electrical machines. Several investigators
      reported that the MF might affect various functions of cells. However, an
      acceptable hypothesis has not yet been proposed. Thus, we studied the effects of
      weak MFs on various biological functions of cells, such as mitochondrial
      functions, stimulation dependent signal transduction of neutrophils, cell growth
      and transformation of HL-60 cells, H(2)O(2)-induced apoptosis and the expression
      of apoptotic genes in HL-60 cells. As a result of the study, a weak MF has
      scarcely any effects on various biological functions of cells. We also studied
      the direct effect of a static strong MF (SSMF, 600-2000 G) on the functions of
      cells or on Fe(2+)-induced lipid peroxidation and on reactive oxygen species
      (ROS) generation in oral polymorphonuclear leukocytes (OPMN) without stimulation
      using Ferrite magnets. The generation of ROS from OPMN was slightly inhibited but
      Fe(2+)-induced lipid peroxidation of biological membrane was slightly stimulated
      by exposure to the SSMF. At present, however, conclusive results have been
      neither obtained experimentally nor any acceptable idea proposed.

PMID- 10927197
TI  - Challenging the culture of sport and alcohol.

PMID- 10927198
TI  - Cocaine misuse treatment in England.
AB  - Three methods were used to identify the treatments given to cocaine misusers in
      England, and to make a preliminary assessment of effectiveness. First, a postal
      survey of all known drug misuse treatment services ascertained approximate
      numbers of cocaine misusers presenting and receiving a specified range of
      treatments. Secondly, staff at selected services were interviewed regarding
      treatment policies, and asked to subjectively rate short-term and long-term
      effectiveness. Thirdly, a cohort of individuals in treatment were studied
      prospectively to assess changes in drug usage and associated problems. Fifty
      percent of services responded to the survey, but there was known to be
      significant duplication in service listings and it is considered that a
      representative pattern of clinical activity has been detected. Approximately half
      those services had recently treated cocaine misusers, mainly using counselling,
      residential rehabilitation, and pharmacological treatments, in which 32 different
      medications were identified. Acupuncture was prominent in a minority of services.
      Staff interviews suggested several principles in managing cocaine misusers, while
      all treatments were rated as being more effective in short-term relief of
      withdrawal features than in enabling longer-term abstinence. The treatment cohort
      were mostly in residential rehabilitation, and marked reductions in drug use and
      related clinical and social problems were demonstrated.

PMID- 10927199
TI  - How the media do drugs: quality control and the reporting of drug issues in the
      UK print media.
AB  - Exaggeration, distortion, inaccuracy, sensationalism; each of these labels has
      been consistently applied to the reporting of drug related issues in the print
      and other media over the last 40 years and beyond. This research sought to
      understand what quality control mechanisms are employed by the UK print media in
      relation to issues related to illicit drugs to ensure accurate, informed and
      appropriate reporting. It was found that the print media in the UK employ almost
      no quality control mechanisms to ensure that such reporting takes place and that
      they predominately rely on the demonstrably insufficient qualities of the 'good
      reporting' skills that journalists bring to their research and writing. What
      concerns did exist regarding accuracy related predominately to protecting the
      publication from being sued for libel and no specific journalistic expertise of
      drug issues was considered necessary. A discussion of these issues is undertaken
      followed by the recommendation for the production of a negotiated media guide.

PMID- 10927200
TI  - Involvement of community pharmacists in the care of drug misusers: pharmacy-based
      supervision of methadone consumption.
AB  - This article examines the feasibility and acceptability of a supervised
      consumption of methadone service from local community pharmacies. It builds upon
      the British Department of Health's recommendations to increase the involvement of
      community pharmacists in the care of addicted drug users and to expand the range
      of services they offer to drug users. The article also takes up the ongoing
      debate on regulating the structure of prescribing and dispensing of methadone and
      the Department of Health's suggestion to consider methods to reduce the diversion
      of methadone, for example via supervised consumption of methadone. The pharmacy
      based supervised self-administration of methadone scheme (SSA) at the Camden and
      Islington Community Health Services Trust Substance Misuse Services (CTDS) in
      London has been found to be valuable by clients, pharmacists and keyworkers. All
      pharmacists involved regarded the project as workable and expressed their
      willingness to continue with the provision of supervised dispensing of methadone
      in the future. Clients stated as main advantages: local access, which saved them
      time and travelling, and the longer opening hours enabled them flexibility in
      managing their time. The main negative comments were related to lack of privacy
      when drinking their methadone within the pharmacy. Most keyworkers welcomed the
      SSA scheme as another dispensing option available. The fact that another
      responsible and accountable health professional was involved was positively
      perceived by the key workers. The Camden and Islington pilot project of providing
      a supervised consumption of methadone service from local community pharmacies has
      successfully put into practice the Department of Health's recommendations to
      increase the involvement of community pharmacists in the care of addicted drug
      users and to expand the involved health range of services they offer to drug
      users. This suggests a positive future for the practice and implementation of
      pharmacy-based self-administered provision of methadone.

PMID- 10927201
TI  - Ibiza uncovered: changes in substance use and sexual behaviour amongst young
      people visiting an international night-life resort.
AB  - Background: Each year more young people travel to international resorts where
      levels of substance use, sex and associated health risks are unknown. This study
      measures changes in levels of substance use and sexual behaviour of young people
      from the UK when on holiday in a youth orientated international resort, Ibiza.
      Methods: Data were collected through a cross-sectional survey collecting matched
      information on individuals' behaviour in the UK and abroad. Questionnaires were
      administered to 846 individuals aged between 15 and 35 at Ibiza Airport prior to
      their returning to the UK. Results: Young visitors to Ibiza significantly alter
      patterns of drug, alcohol and tobacco use. For ecstasy, in the UK 2.9% of users
      (9/313) used 5 or more days a week, while in Ibiza this rises to 42.6% (127/298).
      Fewer individuals use amphetamine, ketamine, cannabis, LSD, cocaine and GHB
      (gamma-hydroxybutyrate) in Ibiza although those continuing to use in Ibiza
      consume at substantially higher rates than when in the UK (P<0.001). Using
      multiple drugs over a 1 or 2 week stay was common (31.9%). Most individuals
      (53.8%) had sex while in Ibiza; 26.2% had sex without a condom and 23.2% had more
      than one sexual partner. Overall, 7.3% of individuals went to hospital or to see
      a doctor while in Ibiza with male (P<0.001), older (P<0.05) and staying for
      shorter times (P<0.005) being the key risk factors. Conclusions: While the
      potential for substance related ill health is dramatically elevated in Ibiza,
      harm minimisation measures in such resorts remain scarce. Equally, although
      holiday companies attract a sexually active cohort, safe sex messages are either
      absent or ineffective. Coordinated information campaigns to protect the health of
      young people are urgently needed and will require European cooperation across
      both public and private organisations.

PMID- 10927203
TI  - Blood management in total knee arthroplasty.

PMID- 10927202
TI  - The Knee - a little progress.

PMID- 10927204
TI  - Towards a better understanding of osteoarthritis of the knee joint.

PMID- 10927205
TI  - Imaging in osteoarthritis: a guide to requesting plain X-rays of the degenerate
      knee.

PMID- 10927206
TI  - The efficacy of autologous blood transfusion in bilateral total knee
      arthroplasty.
AB  - A controlled, randomised, prospective study was undertaken to assess the efficacy
      of the use of a blood re-infusion device in the reduction of allogenic blood
      requirements of patients undergoing bilateral simultaneous total knee
      replacements. Thirty-three consecutive patients were randomised to receive
      allogenic blood only, or a combination of collected and re-infused blood. An
      average of 1000 ml of drainage blood was salvaged in the study group, resulting
      in a significant reduction in allogenic blood requirements from 6.3 to 3.8 units
      in total (P value=0.002). No patients suffered transfusion reactions. We conclude
      that autologous re-infusion is a safe and effective method of reducing allogenic
      blood requirements, and as a result, reducing the risks of transmission of
      infection, and the rate of post-operative infection.

PMID- 10927207
TI  - Uncemented total knee replacement - the favourable influence of low over high
      pressure drainage.
AB  - The post-operative blood loss following an uncemented total knee replacement is
      substantial and can be affected by the vacuum pressure in the suction drains. One
      hundred and nine patients undergoing 122 uncemented total knee replacements were
      monitored to ascertain the influence of high or low vacuum drains on blood loss.
      Low volume drains produced a statistically significant reduction in blood loss
      compared to high vacuum drains [mean 1364 ml vs. mean 1695 ml (P<0.0062)]. Our
      findings revealed that high suction pressure drains are not necessary, and may be
      detrimental when used following uncemented total knee replacement.

PMID- 10927208
TI  - How much blood is really lost in total knee arthroplasty?. Correct blood loss
      management should take hidden loss into account.
AB  - In total knee arthroplasty (TKA) the total blood loss is composed of 'visible'
      blood loss from the surgical field and wound drainage, and blood loss into the
      tissues which is hidden. Blood management should be aimed at addressing the total
      blood loss. The measured loss is generally an underestimation of the 'true' loss,
      which can be calculated. Sixty-three TKAs were prospectively studied at the Avon
      Orthopaedic Centre, Bristol, UK. All but two TKAs were performed under a
      tourniquet. Thus the intraoperative blood loss was usually zero. Reinfusion of
      drained blood was carried out when appropriate. The drainage and volume reinfused
      were recorded. None of the patients studied received a bank blood transfusion.
      All patients had FBC including haematocrit (Hct) pre- and post-operatively. Each
      patients height and weight were recorded pre-operatively. The true total blood
      loss was calculated using height, weight and pre- and post-op Hct. Subtracting
      the visible loss gives the hidden loss. As the object of the study was to
      determine the proportion of blood loss that is hidden, rather than document blood
      loss in general, seven patients with very large blood losses were excluded from
      the study to minimise the effect of haemodilution on our calculation. The
      threshold chosen was 1.5 l. In TKA, the mean total calculated blood loss was 1474
      ml. The mean hidden loss was 735 ml. It can be seen that the hidden loss is 50%
      of the total loss, making the true loss following TKA twice the volume usually
      recorded. This is due to bleeding into the tissues and haemolysis when reinfusion
      is carried out. It is concluded that when planning blood management after TKA,
      account should be taken of the probable substantial hidden blood loss.

PMID- 10927209
TI  - Patient satisfaction needs as related to knee stability and objective findings
      after ACL reconstruction using the LARS artificial ligament.
AB  - The purposes of this study are to compare patient satisfaction with the objective
      measurement of knee stability and assess early complications following ACL
      reconstruction using a LARS artificial ligament. Forty-seven patients were
      reviewed 8-45 months after surgery. Assessment was made by the Knee and
      Osteoarthritis Outcome Score for patient satisfaction, a modified International
      Knee Documentation Committee form for clinical knee stability, and a Telos stress
      radiography for PA stability. Complications were assessed at interview and were
      double-checked with charts. The LARS artificial ligament may be a safe device to
      reconstruct an ACL tear. Documenting mechanical stability of the knee is
      inadequate when reporting follow-up studies and a questionnaire assessing patient
      satisfaction should be added to provide a better picture of the outcome and
      results.

PMID- 10927210
TI  - Treatment of supracondylar femoral fracture above total knee replacement by
      custom made hinged prosthesis.
AB  - A supracondylar fracture above a total knee arthroplasty (TKA) is a devastating
      complication for both the patient and surgeon. Various methods of treatment are
      available. We have treated seven cases of displaced supracondylar fractures above
      a total knee replacement with custom made implants. This technique allows rapid
      post-operative recovery and gives a good functional outcome.

PMID- 10927211
TI  - Infected knee treated by total knee arthroplasty.
AB  - The perceived wisdom in orthopaedics precludes insertion of implants in cases of
      post-recent active joint sepsis. However, revision knee surgery after infected
      arthroplasty has now been recognised to be safe and efficacious in specialised
      centres. We illustrate the concept of using principles of revision surgery to
      successfully treat knees destroyed by primary staphylococcal septic arthritis.

PMID- 10927212
TI  - Long-term results of the Accord total knee replacement in the Countess of Chester
      Hospital.
AB  - Between 1985 and 1996, 74 knees in 61 patients were replaced with a cemented
      Accord total knee arthroplasty at the Countess of Chester Hospital. This
      prosthesis is of an unconstrained meniscal-bearing design. At the time of study,
      16 patients with 20 knees had died, six knees were lost to follow-up and one knee
      had become infected. Twenty-five knees had been revised or undergone further
      surgery (including four knees in deceased patients); these were classed as
      failures. Twenty-four patients with 26 knees still in situ were reviewed between
      July and September 1998. They were assessed clinically according to the Knee
      Society Scoring system and radiographically with weight-bearing antero-posterior
      and lateral films. The mean knee score was 60, and the mean function score was
      42. Of the 25 knees that had failed, 19 had been revised for instability.
      Survivorship was 58% at 10 years with an average follow-up of 5 years 4 months.
      These results are poor compared with those reported on more conventional total
      knee replacements. The authors urge that new implants should be viewed critically
      because of the absence of long-term results, no matter how good their theoretical
      advantages appear to be.

PMID- 10927214
TI  - Wear debris-induced pseudotumour in a cemented total knee replacement.
AB  - We present a case of wear debris-induced osteolysis around the tibial component
      of a cemented total knee replacement associated with an expansile pseudotumour in
      the head of the fibula.

PMID- 10927215
TI  - Stress fracture of the medial tibial condyle.
AB  - Although stress fractures of the tibial diaphysis are common among athletes, the
      proximal tibial metaphysis is an unusual location for such injuries. In addition,
      their proximity to the knee joint can obscure the diagnosis. We present a case of
      a stress fracture of the medial tibial condyle in a long-distance runner, aiming
      to increase awareness about this uncommon and interesting differential diagnostic
      problem. A change in running conditions preceded the fracture and should always
      raise suspicion of overuse injuries. MRI scan has proved very sensitive for
      diagnosing stress fractures and provided a definite diagnosis in our case.

PMID- 10927213
TI  - Resection of degenerate menisci - is it useful?
AB  - Forty-three symptomatic patients, with a pre-operative MRI diagnosis of an
      isolated degenerate tear of the meniscus, treated by Arthroscopic resection were
      reviewed after a minimum follow up of 6 years post-surgery. Pre-operatively there
      was no clinical or radiological evidence of arthroses, but at surgery 65% of
      patients were noted to have varying degrees of articular cartilage changes,
      ranging from Grade I to Grade III according to Outerbridge's classification. Six
      and a half years (range 6-8 years) following Arthroscopic resection of these
      degenerate tears 50% of the patients had moderate to severe pain in the operated
      knee. Their mean Lysholm score was 61.9 (range 11-100, S.D. 27.3) and the median
      current Tegner activity score was 3 (range 0-7, S.D. 1.65) with 86% patients
      having dropped their levels of activities by two grades (1-7) (P=0.0001). The SF
      36 questionnaire revealed a significant difference in the mean scores for Role
      Physical, Role Emotional, Mental Health, Vitality and Bodily Pain categories when
      compared with the mean scores of the general population of similar age and sex
      range. This suggests that the differences arose due to knee symptoms as there was
      no significant difference in the mean General Health Scores for the two
      populations. We conclude that although Arthroscopic resection of these lesions
      may provide relief in the short-term, these benefits are not long lasting.

PMID- 10927216
TI  - Surgical technique tip: prevention of splashback when using pulsed lavage during
      total knee replacement.

PMID- 10927218
TI  - Report of the Executive Committee for 1998.

PMID- 10927222
TI  - Expansion of scalar validation criteria to three dimensions: the R tensor.
      Erratum.
AB  - In the paper by Parkin [Acta Cryst. (2000), A56, 157-162], an incorrect
      correspondence e-mail address is given. The correct address is given above.

PMID- 10927225
TI  - Nonsymmetrical X-ray diffraction in a perfect rectangular t x l crystal.
      Extinction and absorption.
AB  - A theoretical investigation of diffraction in a rectangular t x l crystal for
      nonsymmetrical coplanar scattering has been undertaken. The asymmetry in the
      scattering geometry, measured by an angle gamma, causes different weights for the
      mixed Laue-Bragg contributions to the integrated power. Primary extinction and
      ordinary absorption are only moderately affected when the value of the
      geometrical parameter zeta = (t/l)tanstraight theta(oh) < 1, straight theta(oh)
      being the Bragg angle. For increasing values of zeta and gamma the surface
      integration set-up for the Laue and Bragg regions is extensively changed, leading
      to pronounced effects. Analytical results for the normal absorption factor are
      presented.

PMID- 10927226
TI  - Temperature-dependent X-ray dynamical diffraction: Darwin theory simulations.
AB  - Thermal vibrations destroy the perfect crystalline periodicity generally assumed
      by dynamical diffraction theories. This can lead to some difficulty in deriving
      the temperature dependence of X-ray reflectivity from otherwise perfect crystals.
      This difficulty is overcome here in numerical simulations based on the extended
      Darwin theory, which does not require periodicity. Using Si and Ge as model
      materials, it is shown how to map the lattice vibrations derived from measured
      phonon dispersion curves onto a suitable Darwin model. Good agreement is observed
      with the usual Debye-Waller behavior predicted by standard theories, except at
      high temperatures for high-order reflections. These deviations are discussed in
      terms of a possible breakdown of the ergodic hypothesis for X-ray diffraction.

PMID- 10927227
TI  - Resonant X-ray diffraction in incommensurately modulated crystals. Symmetry
      consideration of anisotropic anomalous scattering.
AB  - Symmetry restrictions on the intensities and polarization properties of main
      reflections and their satellites are found for incommensurately modulated
      crystals in the case of anisotropic anomalous X-ray diffraction near absorption
      edges. It is shown that the modulation becomes a source of additional anisotropy
      for each resonant scatterer and induces a modulated behaviour of the
      susceptibility tensor. The four-dimensional approach is used to calculate the set
      of possible reflections. It is found that additional ('forbidden') reflections
      may appear both in the system of main reflections and in the system of
      satellites. The anisotropy also results in complex azimuthal and polarization
      properties of each reflection. The displacive modulation is discussed in detail.
      The ATS reflections corresponding to the resonant X-ray diffraction near the K
      edge of iron in pyrrhotite-5.5C are considered.

PMID- 10927228
TI  - Influence of intermolecular interactions on multipole-refined electron densities.
AB  - This work examines the effect of intermolecular interactions on molecular
      properties derived from simulated X-ray diffraction data. Model X-ray data are
      computed from a superposition of ab initio molecular electron densities in the
      crystal, as well as from periodic crystal Hartree-Fock electron densities, for
      the hydrogen-bonded systems ice VIII, formamide and urea, as well as the weakly
      bound acetylene. The effects of intermolecular interactions on the electron
      density are illustrated at both infinite and finite data resolution, and it is
      concluded that multipole models are capable of quantitative retrieval of the
      interaction density, despite the known shortcomings of the radial functions in
      the model. Multipole refinement reveals considerable enhancement of the molecular
      dipole moment for hydrogen-bonded crystals, and negligible change in molecular
      second moments. Electric field gradients at H nuclei are significantly reduced in
      magnitude upon hydrogen bonding, and this change is also faithfully represented
      by the rigid pseudoatom model.

PMID- 10927229
TI  - The periodic average structure of particular quasicrystals.
AB  - The non-crystallographic symmetry of d-dimensional (dD) quasiperiodic structures
      is incompatible with lattice periodicity in dD physical space. However, dD
      quasiperiodic structures can be described as irrational sections of nD (n > d)
      periodic hypercrystal structures. By appropriate oblique projection of particular
      hypercrystal structures onto physical space, discrete periodic average structures
      can be obtained. The boundaries of the projected atomic surfaces give the maximum
      distance of each atom in a quasiperiodic structure from the vertices of the
      reference lattice of its average structure. These maximum distances turn out to
      be smaller than even the shortest atomic bond lengths. The metrics of the average
      structure of a 3D Ammann tiling, for instance, with edge lengths of the unit
      tiles equal to the bond lengths in elemental aluminium, correspond almost exactly
      to the metrics of face-centred-cubic aluminium. This is remarkable since most
      stable quasicrystals contain aluminium as the main constitutent. The study of the
      average structure of quasicrystals can be a valuable aid to the elucidation of
      the geometry of quasicrystal-to-crystal transformations. It can also contribute
      to the derivation of the physically most relevant Brillouin (Jones) zone.

PMID- 10927230
TI  - Minimal surfaces with self-intersections along straight lines. I. Derivation and
      properties.
AB  - A special kind of three-periodic minimal surface has been studied, namely
      surfaces that are generated from disc-like-spanned skew polygons and that
      intersect themselves exclusively along straight lines. A new procedure for their
      derivation is introduced in this paper. Several properties of each such surface
      may be deduced from its generating polygon: the full symmetry group of the
      surface, its orientability, the symmetry group of the oriented surface, the
      pattern of self-intersections, the branch points of the surface, the symmetry and
      periodicity of the spatial subunits demarcated by the surface, and the Euler
      characteristics both of the surface and of the spatial subunits. The
      corresponding procedures are described and illustrated by examples.

PMID- 10927231
TI  - Comments on the characteristics of incommensurate modulation in quartz:
      discussion about a neutron scattering experiment.
AB  - From analysis of the elastic neutron scattering data of Dolino et al. [J. Phys.
      (Paris) (1984), 45, 361-371], it is shown that, besides the well identified
      components u(x) and u(y) of the acoustic displacements in the incommensurate (IC)
      phase of quartz, there also exists a strong component of the u(z) vector of the
      modulation. The existence of the large u(z) is not consistent with the currently
      accepted model for the IC transition in quartz, since the long-period IC
      modulation observed in quartz cannot induce any noticeable acoustic component
      u(z). The need for a new model is keenly felt in order to understand the origin
      of the IC modulation in quartz.

PMID- 10927232
TI  - A multisolution method of phase determination by combined maximization of entropy
      and likelihood. VI. The use of error-correcting codes as a source of phase
      permutation and their application to the phase problem in powder, electron and
      macromolecular crystallography.
AB  - The use of error-correcting codes as a source of efficient designs of phase
      permutation schemes is described. Three codes are used, all taken from the
      Bricogne BUSTER program [Bricogne (1993). Acta Cryst. D49, 37-60]: the Hamming
      [7, 4, 3], the Nordstrom-Robinson (16, 256, 6) and the Golay [24, 12, 8] or its
      punctured [23, 12, 7] form. These are used in a maximum-entropy-likelihood
      phasing environment to carry out phase permutation of basis-set reflections
      instead of the usual quadrant permutation or magic integer approaches. The use of
      codes in this way inevitably introduces some errors in the phase choices, but for
      most structures this is not significant especially when the gain in sampling
      efficiency is considered. For example, the Golay [24, 14, 8] allows the
      permutation of 24 centric phases in such a way that only 4096 phase sets are
      produced instead of 2(24) = 16777216, and one of these sets has, at most, only
      four wrong phases. The method is successfully applied to three powder diffraction
      data sets of increasing complexity, and with increasing degrees of overlap
      {Mg(3)BN(3), Sigma-2 ([Si(64)O(128)].4C(10)H(17)N) and the NU-3 zeolite}, a
      sparse electron diffraction data set for buckminsterfullerene, C(60), and the
      small protein molecule crambin at 3 A resolution where 42 reflections are phased
      with a Uweighted mean phase error of 58.5 degrees.

PMID- 10927236
TI  - International Union of Crystallography Acta Crystallographica Section A Notes for
      Authors.

PMID- 10927233
TI  - On the prediction of crystal morphology. III. Equilibrium and growth behaviour of
      crystal faces containing multiple connected nets.
AB  - In this paper, the equilibrium and growth behaviour of faces (hkl) with more than
      one connected net is studied. It is shown that for these types of orientation
      different surface phases exist under equilibrium conditions as a function of
      temperature. Depending on the exact bonding topology at the surface, flat, rough
      or disordered flat phases are found. Moreover, the growth rate R(hkl) of such
      faces can differ significantly from the usually calculated relative growth rates
      based on the attachment energy. Monte Carlo simulations confirm the results from
      the Hartman-Perdok analyses and offer a tool for the prediction of the crystal
      habit as a function of supersaturation.

PMID- 10927237
TI  - International Union of Crystallography Transfer of Copyright Agreement.

PMID- 10927238
TI  - Professor Alexander F. Moodie 75 years.

PMID- 10927239
TI  - Retrieval of the projected potential by inversion from the scattering matrix in
      electron-crystal scattering.
AB  - The retrieval of a unique crystal potential from the scattering matrix S in high
      energy transmission electron diffraction is discussed. It is shown that, in
      general, data taken at a single orientation are not sufficient to determine all
      the elements of S. Additional measurements with tilted incident beam are required
      for the determination of the whole S matrix. An algorithm for the extraction of
      the crystal potential from the S matrix measured at a single energy and thickness
      is presented. The limiting case of thin crystals is discussed. Several examples
      with simulated data are considered.

PMID- 10927240
TI  - Dynamic inversion by the method of generalized projections.
AB  - A new approach to the inversion problem of dynamical transmission electron
      diffraction is described, based on the method of generalized projections in set
      theory. An algorithm is described that projects between two sets of constrained
      scattering matrices. This iterative process can be shown to converge, giving the
      required structure factors (for some choice of origin) if the sets are convex.
      For the dynamical inversion problem, the set topology is that of an N(2) torus,
      the sets are not convex, and traps are therefore sometimes encountered. These can
      be distinguished from solutions, allowing the algorithm to be restarted until a
      solution is found. Examples of successful inversion from simulated multiple
      scattering data are given, which therefore solve the phase problem of electron
      diffraction for centrosymmetric or noncentrosymmetric crystal structures. The
      method may also be useful for the three-beam X-ray diffraction problem.

PMID- 10927241
TI  - Simulations for imaging with atomic focusers.
AB  - The basis has been explored for the possible application of the various schemes
      that have been proposed for making use of the focusing properties of single heavy
      atoms, or rows of atoms extending through thin crystals in axial directions, for
      the attainment of ultra-high resolution in electron microscopy. Calculations are
      reported for the form of 200 keV electron beams channeled along rows of atoms
      through crystals and propagated in the vacuum beyond the crystals. The conditions
      for forming beams less than 0.05 nm in diameter have been established.
      Simulations of images having resolutions of this order are reported for the case
      that the specimen is placed at the Fourier image position beyond the exit face of
      a thin crystal and the transmission of the periodic array of ultra-fine beams,
      translated laterally by tilting the incident beam, may be observable using a
      conventional transmission-electron-microscopy (TEM) instrument.

PMID- 10927242
TI  - A study of Li2TiOSiO4 and Li2TiOGeO4 by X-ray powder and electron single-crystal
      diffraction, 17O MAS NMR andO K-edge and Ti L2,3-edge EELS.
AB  - X-ray powder and electron single-crystal diffraction of crystals of
      Li(2)TiOSiO(4) and Li(2)TiOGeO(4) showed them to be tetragonal, space group
      P4/nmm unit-cell parameters a = 6.4379(2), c = 4.40032(2) A for Li(2)TiOSiO(4)
      and a = 6.6110(8), c = 4.4372(6) A for Li(2)TiGeO(4). The compounds are
      isostructural with their sodium analogues but are considerably compressed along
      the c axis owing to the smaller size of lithium compared with sodium atoms.
      Square-pyramidal TiO(5) groups are joined in these compounds by tetrahedral
      SiO(4) and GeO(4) groups, respectively. (17)O nuclear magnetic resonance spectra
      of the two compounds, isotopically enriched with (17)O, showed peaks due to the
      apical titanyl, Ti-O, and basal, bridging, Ti-O-Si or Ti-O-Ge, oxygen atoms of
      the title compounds. By comparison with reference spectra, oxygen K edges and
      titanium L(2,3) edges of electron energy-loss spectra were tentatively assigned.

PMID- 10927243
TI  - Real-space Green's-function approach within RHEED.
AB  - Green's-function techniques are used to obtain a real-space series solution for
      the elastic reflection high-energy electron diffraction (RHEED) from a
      crystalline surface. A renormalized perturbation expansion due to potential self
      scattering is developed for the local real-space Green's function. With the Pt
      (111) surface as an example, numerical results are obtained for reflection
      coefficients and intensities. In particular, calculations are performed to obtain
      the local density of states at and near the surface region. Total density-of
      states calculations are also performed. These provide a basis for a discussion of
      the form of resonant electronic Green's functions that can be used to describe
      the surface resonance phenomenon within RHEED.

PMID- 10927244
TI  - High-resolution electron-microscope images of crystals with correlated atomic
      displacements.
AB  - A coordinate-space multislice description of the scattering of high-energy
      electrons is constructed from consecutions of differential operators acting upon
      atomic potentials. It is used to find expressions for the intensity distribution
      in high-resolution electron-microscope images of crystals whose atoms are
      periodically displaced relative to a reference lattice according to a modulation
      wave. Both static correlated displacements, such as occur in modulated
      structures, and time-dependent correlated displacements, as are generated by
      phonons, are considered. Two aspects of the image are examined in detail; its
      translational symmetry and its dependence upon the correlations between the
      atomic displacements. It is shown that the intensity distribution due to
      scattering from static correlated displacements has the translational symmetry of
      the modulated structure in that projection, as determined by the component of the
      modulation wavevector perpendicular to the incident beam, whereas that due to
      scattering from phonons has the translational symmetry of the reference lattice
      in that projection. The former is a consequence of higher-order Laue-zone
      interactions. The intensity distribution due to scattering from static
      displacements depends upon the absolute phase of the displacement at each
      scattering atomic site whereas that due to scattering from phonons depends only
      upon the relative phase of the displacements between different scattering sites,
      both within the same atomic column parallel to the beam and in adjacent columns.
      In both cases, the influence of the component of the correlation wavevector
      parallel to the incident beam is different to that perpendicular to the beam; the
      former affects the intensity mostly at the atomic sites whilst the latter affects
      the intensity mostly between the atomic sites. It is also observed that, as a
      consequence of the periodic nature of the polarization-vector function, the
      interference terms are small, both relative to the non-interference term and in
      an absolute sense, particularly for phonon scattering. For this reason, the
      contribution to the image due to scattering from correlated atomic displacements
      will have greater and sharper atomic contrast than that due to scattering from
      the reference structure without displacements. In addition, this component of the
      intensity distribution will not exhibit strong contrast reversal when the
      objective-lens defocus is changed.

PMID- 10927245
TI  - Schemes to determine the crystal potential under dynamical conditions using
      voltage variation.
AB  - Charge densities and crystal structures can be determined routinely from X-ray
      diffraction as X-ray scattering is relatively weak and single scattering can be
      assumed. The strong dynamical diffraction of high-energy electrons has prevented
      electron diffraction from being used in the same way. Dynamical diffraction
      describes both the propagation of the Bragg diffracted wave in the crystal and
      the scattering by the crystal potential. The balance between these two processes
      changes as a function of voltage due to relativistic effects. The difference in
      diffracted intensities recorded at two voltages is shown to be directly
      proportional to the crystal potential. This is confirmed by calculations using
      first-order perturbation theory which show negligible differences compared to
      exact calculation. It should therefore be possible to use differences in
      intensity measured as a function of voltage to determine the crystal potential
      directly. If the full complex wave function is available, then there is a
      particularly simple procedure to recover the potential, even under dynamical
      conditions.

PMID- 10927246
TI  - Boron nitride cones: structure determination by transmission electron microscopy.
AB  - A form of turbostratic boron nitride containing a large percentage of micrometre
      size conically shaped particles was investigated by transmission electron
      microscopy. Electron diffraction patterns revealed the presence of correlations
      between adjacent boron nitride layers. The diffraction patterns were also used to
      determine the cone apex angle of many cone-like objects. The apex angles
      exhibited a broad distribution from 84 to 130 degrees with an ill defined peak in
      the 92-95 degrees region. These results could be accounted for by a structure
      model in which conical boron nitride layers are helically wound about a
      disclination axis, according to overlap angles that correspond to high densities
      of coincidental lattice sites between successive layers. The clustering of the
      apex angles near 93 degrees was attributed to the formation of a square ring
      during the nucleation stage. This appears to be specific to the boron nitride
      system.

PMID- 10927247
TI  - Experimental and theoretical characterization of structure in thin disordered
      films.
AB  - The electron microscope provides an ideal environment for the structural analysis
      of small volumes of amorphous and polycrystalline materials by enabling the
      collection of scattering information as a function of energy loss and momentum
      transfer. The scattered intensity at zero energy loss can be readily processed to
      a reduced density function, providing information on nearest-neighbour distances
      and bond angles. A method for collecting and processing the scattered intensity,
      which allows for the collection of an energy-loss spectrum for a range of
      momentum transfers, is discussed. A detailed structural determination from a
      reduced density function alone is difficult and it is shown that a more detailed
      structural model can be obtained by combining the experimental reduced density
      function with model structures obtained from molecular dynamics based on first
      principles quantum mechanics. This method is applied to tetrahedral amorphous
      carbon, as an example of a monatomic network, and to aluminium nitride, as a
      prototype for a binary amorphous alloy.

PMID- 10927248
TI  - Three-phase structure invariants and structure factors determined with the
      quantitative convergent-beam electron diffraction method.
AB  - Quantitative convergent-beam electron diffraction is used to determine structure
      factors and three-phase structure invariants. The refinements are based on centre
      disc intensities only. An algorithm for param-eter-sensitive pixel sampling of
      experimental intensities is implemented in the refinement procedure to increase
      sensitivity and computer speed. Typical three-beam effects are illustrated for
      the centrosymmetric case. The modified refinement method is applied to determine
      amplitudes and three-phase structure invariants in noncentrosymmetric InP. The
      accuracy of the results is shown to depend on the choice of the initial
      parameters in the refinement. Even unrealistic starting assumptions and incorrect
      temperature factor lead to stable results for the structure invariant. The
      examples show that the accuracy varies from 1 to 10 degrees in the electron three
      phase invariants determined and from 0.5 to 5% for the amplitudes. Individual
      phases could not be determined in the present case owing to spatial intensity
      correlations between phase-sensitive pixels. However, for the three-phase
      structure invariant, stable solutions were found.

PMID- 10927249
TI  - A 'three-beam' analysis of resonance scattering in reflection high-energy
      electron diffraction.
AB  - Enhanced reflection of fast electrons from a crystal surface and a decrease in
      the depth of penetration of the primary beam occurs when diffraction conditions
      are such as to set up a wave travelling just beneath the crystal surface. This is
      the surface resonance condition for reflection high-energy electron diffraction
      (RHEED). Quantitative prediction of these effects can be achieved by assuming
      that only the primary and two diffracted beams are significant. Expressions for
      the coefficient of reflection and the depth of penetration in terms of a few
      Fourier coefficients of an effective potential are derived. These coefficients
      depend sensitively on incident-beam direction and are significantly different
      from the values for the bulk crystal. In particular, the mean potential
      experienced by the electrons in the resonance state is increased. It can be
      estimated using Bethe's perturbation approach. Predictions of the position,
      height and width of the peak in reflectivity resulting from resonance scattering
      from the (111) surface of platinum are in reasonable agreement with the values
      obtained from many-beam computations. The three-beam approach gives insight into
      resonance scattering using the standard formalism of diffraction theory.

PMID- 10927250
TI  - Divergent-beam technique used in a SEM to measure the cell parameters of
      isotopically distinct samples of LiF over the temperature range approximately 15
      375 K.
AB  - The cell parameters for LiF containing 90.4% (6)Li and 50.2% (6)Li were
      determined from a series of divergent-beam photographs taken at approximately 25
      K intervals in the approximately 15 to 375 K range. The divergent-beam
      photographs were generated in a Stereoscan S4 scanning electron microscope fitted
      with a liquid-helium cold finger and a Dingley Kossel camera. Lattice parameters
      can be determined from the ratios of lines joining conic intersections, and such
      data, measured on films taken at known temperatures, were correlated with
      equivalent data from computer-generated divergent-beam patterns using appropriate
      cell parameters; our cell parameters at 298 K are (6)Li(90.4%) = 4.0272(2) and
      (6)Li(50.2%) = 4.0266(2) A. If it is assumed that the stated isotopic
      compositions are correct, linear extrapolation to end-member cell parameters
      gives (6)Li(100%) = 4.0273 (2) and (6)Li(0%) = 4.0259(2) A. Since for a cubic
      crystal only one lattice-parameter measurement is required from each photograph,
      the usefulness of the ratio approach was tested by comparing values of the
      lattice parameter deduced from many such ratios obtained from photographs with no
      symmetry and with mirror symmetry.

PMID- 10927251
TI  - Towards an exit wave in closed analytical form.
AB  - A simple but sufficiently accurate expression is obtained for the exit wave of a
      crystal in zone-axis orientation. The exit wave at each atom column can be
      parametrized with only one parameter, which is a function of the projected
      'weight' of the column.

PMID- 10927252
TI  - The role of projection operators in the theory of N-beam diffraction and the
      inversion of three-beam elastic scattering intensities.
AB  - Commencing from a projection-operator description of N-beam diffraction, the
      mathematical basis for the recovery of phase and amplitude information from a
      three-beam convergent-beam electron diffraction pattern is given for both the
      centrosymmetric and noncentrosymmetric cases. The algebra is available in
      Mathematica Notebook form from the URL
      ftp://ftp.physics.uwa.edu.au/pub/EMC/3BeamAlgebra.nb.

PMID- 10927253
TI  - Disorder, superlattice canting and chiral domains in zirconia-niobia ceramic
      alloys.
AB  - The structures of the zirconia-based ceramic oxide superlattice alloy phases
      Nb(2)Zr(x-2)O(2x+1) (x approximately 7-12) are reviewed. It is noted that recent
      investigations into the alloys' structure suggest they are not strictly
      crystalline, with consequences for their diffraction properties. It is suggested
      that several aspects of their behaviour may be interpreted as proper to a
      frustrated two-dimensional XY model, where the distinctive planes of oxygen atoms
      in the alloys form a lattice of planar XY 'spins'. Evidence is presented for the
      existence of frustration, which produces superlattice canting in the model
      including electron-microscope evidence for the existence of domains of staggered
      Ising-type chirality in the alloys, as predicted for the frustrated two
      dimensional XY model by Villain [J. Phys. C (1977), 10, 1717-1734].

PMID- 10927254
TI  - A two-phase charge-density real-space-pairing model of high-Tc superconductivity.
AB  - It is usually assumed that high-T(c) superconductors have a periodic band
      structure and a periodic charge density, although amorphous low-T(c)
      superconductors are known. In this paper, it is suggested that the CuO(2)
      conduction planes of cuprate superconductors consist of regions of two different
      charge densities which do not normally repeat periodically. It is suggested that
      the pairing of holes occurs in real space in cuprate superconductors. It is
      proposed that the hole-pairing mechanism is magnetic exchange coupling and the
      pairing force is strong, the pairing energy being greater than kT at room
      temperature. The bound hole pair is essentially a bipolaron. A real-space model
      is very tentatively suggested in which the CuO(2) planes of YBa(2)Cu(3)O(7)
      contain nanodomains of a 3 x 3 hole lattice surrounded by interfaces one unit
      cell wide in which the holes are paired. In the superconducting state in this
      model, the existing hole pairs condense and move coherently and collectively
      around the insulating nanodomains, like trams running around blocks of houses,
      with one hole on each tramline. The hole pairs move in an elegant manner with
      hole pairs hopping from oxygen to oxygen via adjacent copper sites. The model
      explains the superconducting current being in the ab plane and it also explains
      the very short coherence lengths. Because the pairing force is strong, the model
      suggests that room-temperature superconductivity might be possible in carefully
      designed new oxide materials.

PMID- 10927255
TI  - Decoherence in electron backscattering by kinked dislocations.
AB  - A model is proposed that explains the origin of the bright contrast of
      dislocation walls consisting of edge dislocation dipoles in electron channelling
      contrast images (ECCI) of fatigued crystals, when the incident beam is parallel
      to the edge dislocations. The model is based on the assumption that the contrast
      arises from the dislocation segments terminating the dipoles. These are modelled
      as screw-type kinks which scatter electrons. Scattering by randomly distributed
      kinks leads to the randomization of phase of transmitted and diffracted beams and
      suppresses the anomalous transmission of electrons. The predicted behaviour of
      electron-channeling contrast images agrees well with experimental
      observations.With apologies for using two beams instead of three!

PMID- 10927256
TI  - X-ray multislice computation using the Moodie-Wagenfeld equations: divergent-beam
      pattern simulation in three-beam and six-beam Laue cases.
AB  - Pattern simulations for three-beam and six-beam X-ray diffraction are presented
      using multislice calculations based on Moodie & Wagenfeld's formulation of the X
      ray equations, which factorize Maxwell's equations into Dirac format, using
      circular-polarization bases. The results are presented in three forms: one
      dimensional rocking curves, Pendellosung thickness fringes, and
      convergent/divergent-beam patterns of single-diffraction orders, using experience
      gained from CBED (convergent-beam electron diffraction) and LACBED (large-angle
      CBED) techniques developed for high-voltage electron diffraction transmission
      patterns. This latter and quite new technique displays the results in the most
      compact form. The acronym DBXRAD (divergent-beam X-ray diffraction) is used for
      these patterns. The optics required for these patterns has only recently become
      available for radiations up to Mo Kalpha(1) in energy and for limited angular
      divergences, but with capillary focusing currently undergoing rapid development
      these limits are likely to be extended. However, these simulations define
      critical angular ranges within reach of current designs. Simulations for light-
      and heavy-atom structures belonging to the enantiomorphic space-group pair
      P3(1)21 and P3(2)21 provide clear evidence of chiral interaction between
      radiation and structure, highlighting divergences from the use in structure
      analysis of the well studied CBED pattern symmetries. Mo Kalpha(1) and Ta
      Kalpha(1) wavelengths were used to minimize absorption for the two structures
      studied, an important factor owing to the large thicknesses (up to 20 mm)
      required.

PMID- 10927257
TI  - Application of the statistical dynamical theory to gamma-ray diffraction
      experiments on low-dislocation quartz single crystals.
AB  - Highly monochromatic (Deltalambda/lambda = 10(-6)) short-wavelength (lambda =
      0.03 A) gamma radiation has been used in the study of the diffraction processes
      in real single crystals. Dislocation-free silicon crystals and quartz crystals
      with small concentrations of chaotically distributed dislocations were
      investigated. The experimental results were processed with use of statistical
      dynamical theories of diffraction, both fundamental and advanced. It is shown
      that the advanced version is more reliable in both cases. However, the values of
      the average lattice phase E, describing the long-range distortions of the
      lattice, can differ markedly from the value of 1 for quartz crystals, and
      parameter L = -ln(E) has a square dependence on the extinction length.

PMID- 10927258
TI  - X-ray standing wave as a result of only the imaginary part of the atomic
      scattering factor.
AB  - The X-ray standing wave has been studied when the real part of the scattering
      factor is zero. In the symmetric Laue case, the phase of the standing wave
      advances by pi when the deviation parameter W changes from -1 to 1, which is the
      same variation as in the usual symmetric Bragg case when only the real part of
      the scattering factor exists. However, the phase in the former case is different
      from that in the latter by pi/2. By using the standing waves, the origins of the
      anomalous transmission and anomalous absorption effects reported by Fukamachi &
      Kawamura [Acta Cryst. (1993), A49, 384-388] have been analysed. The standing wave
      in the Laue case can give rise to a more accurate method of site determination of
      a specified impurity atom as well as a wider range of applications than a
      conventional standing-wave approach.

PMID- 10927259
TI  - Geometrical effects in diffraction analysis.
AB  - The use of X-ray and neutron scattering as a tool to study phase transitions is
      well established. As techniques improve and experiments are made under
      successively higher resolution, the need to consider the role of both the
      distribution of diffracting length scales and the incident-beam coherence volume
      is emphasized. The interplay of diffracting length scales and the beam coherence
      volume no longer permits calculation of diffraction profiles in terms of the
      sample intensity response convolved with an instrumental resolution function.
      Rather, the probe and sample now enter the calculation on an equal footing at the
      level of the scattering amplitudes. Under these conditions, it is found that the
      summation of coherent scattering amplitudes leads to characteristic profiles in
      wave-vector and, in the case of resonant X-ray scattering, energy space. In this
      latter case, in the vicinity of strong absorption edges, as used for example in
      resonant magnetic X-ray diffraction, the energy dependence of diffraction
      profiles may uniquely allow spatial localization of the scattering volume below
      the sample surface. This observation may considerably augment the range and power
      of resonant X-ray scattering.

PMID- 10927260
TI  - Elastic scattering of partially coherent beams of fast electrons by a crystal
      with a defect.
AB  - Scattering of a quasi-monochromatic electron beam by a crystal with a defect is
      described with the use of the mutual coherency function and the formalism of
      quasi-Bloch waves. An expression correlating the mutual intensity on the exit and
      entrance surfaces of the crystal in terms of the scattering matrix has been
      found. The matrix elements are determined by a system of integro-differential
      equations, which have been obtained without using the column approximation. It
      has been shown that calculations of the matrix elements can be significantly
      simplified when the approximation of the small-angle scattering of quasi-Bloch
      waves by the defect displacement field is satisfied. Such an approximation can be
      applied in many cases, e.g. to a crystal with a dislocation. The mutual intensity
      on the crystal entrance surface has been found for the general case of defocused
      illumination. As an example of applying the new approach, expressions for the
      intensity in convergent-beam electron diffraction (CBED) and large-angle CBED
      (LACBED) patterns have been obtained. The LACBED patterns of a crystal with a
      dislocation have been simulated. It has been shown that the developed approach
      allows a more exact simulation of the LACBED than do the conventional approaches
      using the column approximation and the approximation of independent plane waves
      filling the illumination cone.

PMID- 10927262
TI  - The probability distribution of structure factors with non-integral indices. II.
      The P1; case.
AB  - The probability distribution of the structure factors with non-integral indices
      is derived in P1;. For integral values of at least one of the indices, the
      intensity distribution coincides with that provided by Wilson's statistics, but
      may strongly differ when the indices are (or are close to) half-integers. The
      deviations are stronger when the integral part of the indices is small, and
      increase with the size of the structure. In favourable circumstances, moduli and
      phases of the reflections may be accurately estimated.

PMID- 10927261
TI  - Chemical bonding effects in the determination of protein structures by electron
      crystallography.
AB  - Scattering of electrons is affected by the distribution of valence electrons that
      participate in chemical bonding and thus change the electrostatic shielding of
      the nucleus. This effect is particularly significant for low-angle scattering.
      Thus, while chemical bonding effects are difficult to measure with small-unit
      cell materials, they can be substantial in the study of proteins by electron
      crystallography. This work investigates the magnitude of chemical bonding effects
      for a representative collection of protein fragments and a model ligand for
      nucleotide-binding proteins within the resolution range generally used in
      determining protein structures by electron crystallography. Electrostatic
      potentials were calculated by ab initio methods for both the test molecules and
      for superpositions of their free atoms. Differences in scattering amplitudes can
      be well over 10% in the resolution range below 5 A and are especially large in
      the case of ionized side chains and ligands. We conclude that the use of molecule
      based scattering factors can provide a much more accurate representation of the
      low-resolution data obtained in electron crystallographic studies. The comparison
      of neutral and ionic structure factors at resolutions below 5 A can also provide
      a sensitive determination of charge states, important for biological function,
      that is not accessible from X-ray crystallographic measurements.

PMID- 10927263
TI  - The probability distribution function of structure factors with non-integral
      indices. III. The joint probability distribution in the P1; case.
AB  - The joint probability distribution function method has been developed in P1; for
      reflections with rational indices. The positional atomic parameters are
      considered to be the primitive random variables, uniformly distributed in the
      interval (0, 1), while the reflection indices are kept fixed. Owing to the
      rationality of the indices, distributions like P(F(p1), F(p2)) are found to be
      useful for phasing purposes, where p1 and p2 are any pair of vectorial indices. A
      variety of conditional distributions like P(|F(p1)| | |F(p2)|), P(|F(p1)|
      |F(p2)), P(varphi(p1)| |F(p1)|, F(p2)) are derived, which are able to estimate
      the modulus and phase of F(p1) given the modulus and/or phase of F(p2). The
      method has been generalized to handle the joint probability distribution of any
      set of structure factors, i.e. the distributions P(F(1), F(2),ellipsis, F(n+1)),
      P(|F(1)| |F(2),ellipsis, F(n+1)) and P(varphi(1)| |F|(1), F(2),ellipsis, F(n+1))
      have been obtained. Some practical tests prove the efficiency of the method.

PMID- 10927264
TI  - Enumeration of four-connected three-dimensional nets. I. Conversion of all edges
      of simple three-connected two-dimensional nets into crankshaft chains.
AB  - Various topological approaches to mathematical analysis, classification and
      enumeration of four-connected three-dimensional (3D) nets are listed. Four
      connected 3D nets are being generated systematically by conversion of edges of a
      vertical stack of congruent three-connected two-dimensional (2D) nets into
      chains. This paper describes 57 3D nets obtained by converting into crankshaft
      chains all edges of the simpler 2D nets in the catalog of the Consortium of
      Theoretical Frameworks. Atomic coordinates are given for distance-least-squares
      modeling in the highest space group. Nine nets occur in known structures:
      tridymite, Zn(2)P(2)O(8).organic, aluminophosphates AlPO-5 (International Zeolite
      Association Structure Commission code AFI), AlPO-8 (AEI), AlPO-11 (AEL), AlPO-25
      (ATV), AlPO-41 (AFO), AlPO-54 (VFI) and AlPO-H2 (AHT).

PMID- 10927265
TI  - Enumeration of four-connected three-dimensional nets. II. Conversion of edges of
      three-connected 2D nets into zigzag chains.
AB  - Four-connected three-dimensional (3D) nets were systematically enumerated by
      converting some horizontal edges of a vertical stack of three-connected two
      dimensional (2D) nets into vertical zigzag chains. 77 out of 131 2D nets were
      selected for enumeration, and different arrangements of zigzag edges and
      horizontal edges were investigated. This yielded 138 3D nets of which 19 are
      represented by known structures: cristobalite; tridymite; MAPO-39 (International
      Zeolite Association Structure Commission code ATN); svyatoslavite; Li-A(BW)
      (ABW); cancrinite (CAN); AlPO-31 (ATO); MAPO-36 (ATS); BaFe(2)O(4); 'nepheline
      hydrate' (JBW); bikitaite (BIK); KBGe(2)O(6); CsAlSi(5)O(12) (CAS); UiO-6 (OSI);
      Theta-1 (TON); ZSM-12 (MTW); ZSM-23 (MTT); AlPO-53C; and CIT-5 (CFI).

PMID- 10927266
TI  - Enumeration of four-connected three-dimensional nets. III. Conversion of edges of
      three-connected two-dimensional nets into saw chains.
AB  - A three-repeat saw (s) chain has each vertical edge separated by a tooth composed
      of two tilted edges zig and zag. Some horizontal (h) edges from a parallel stack
      of three-connected two-dimensional (2D) nets can be converted into an s chain.
      Each resulting four-connected vertex in the three-dimensional (3D) net may be
      part of either one, two or three s chains. The first type of (h,s)* 3D net is
      related by a sigma-type mirror plane to a (h,z)* net listed in paper II [Han &
      Smith (1998). Acta Cryst. A55, 342-359]. The second type does not have an (h,z)*
      relative. Using the same three-connected 2D nets as in paper II, 174 four
      connected 3D nets were selected from the first two types, including six in known
      structures: 'nepheline hydrate' (International Zeolite Association Structure
      Commission code JBW), AlPO(4)-12-TAMU (ATT), offretite (OFF), Linde Type L (LTL),
      SUZ-4 (SZF) and ZSM-10 (ZST). The third type with three back-to-back s chains is
      represented by edingtonite (EDI), and systematic enumeration is in progress. The
      geometrical and topological properties of the 3D nets are given. Idealized unit
      cell data and atomic coordinates for tetrahedral bonding were obtained for 40
      selected 3D nets by distance-least-squares (DLS) refinement.

PMID- 10927267
TI  - Algorithms for deriving crystallographic space-group information.
AB  - Algorithms are presented for three-dimensional crystallographic space groups,
      handling tasks such as the generation of symmetry operations, the
      characterization of symmetry operations (determination of rotation-part type,
      axis direction, sense of rotation, screw or glide part and location part), the
      determination of space-group type [identified by the space-group number of the
      International Tables for Crystallography (Dordrecht: Kluwer Academic Publishers)]
      and the generation of structure-seminvariant vectors and moduli. The latter are
      an algebraic description of allowed origin shifts, which are important in crystal
      structure determination methods or for comparing crystal structures. The space
      group type determination produces a change-of-basis matrix which transforms a
      given space-group representation to the standard one according to the
      International Tables for Crystallography. The algorithms were implemented and
      tested using the SgInfo library. The source code is free for non-commercial
      applications.

PMID- 10927268
TI  - Probability distribution of the four-phase structure invariants of isomorphously
      related structure factors and its applications.
AB  - The probability distribution of the four-phase structure invariants (4PSIs)
      involving four pairs of structure factors is derived by integrating the direct
      methods with isomorphous replacement (IR). A simple expression of the reliability
      parameter for 16 types of invariant is given in the case of a native protein and
      a heavy-atom derivative. Test calculations on a protein and its heavy-atom
      derivative using experimental diffraction data show that the reliability for 4PSI
      estimates is comparable with that for the three-phase structure invariants
      (3PSIs), and that a large-modulus invariants method can be used to improve the
      accuracy.

PMID- 10927270
TI  - A feasible set approach to the crystallographic phase problem.
AB  - The connection between the crystallographic phase problem and the feasible set
      approach is explored. It is argued that solving the crystallographic phase
      problem is formally equivalent to a feasible set problem using a statistical
      operator interpretable via a log-likelihood functional, projection onto the non
      convex set of experimental structure factors coupled with a phase-extension
      constraint and mapping onto atomic positions. In no way does this disagree with
      or dispute any of the existing statistical relationships available in the
      literature; instead it expands understanding of how the algorithms work. Making
      this connection opens the door to the application of a number of well developed
      mathematical tools in functional analysis. Furthermore, a number of known results
      in image recovery can be exploited both to optimize existing algorithms and to
      develop new and improved algorithms.

PMID- 10927271
TI  - The Darwin procedure in optics of layered media and the matrix theory.
AB  - The Darwin dynamical theory of diffraction for two beams yields a nonhomogeneous
      system of linear algebraic equations with a tridiagonal matrix. It is shown that
      different formulae of the two-beam Darwin theory can be obtained by a uniform
      view of the basic properties of tridiagonal matrices, their determinants
      (continuants) and their close relationship to continued fractions and difference
      equations. Some remarks concerning the relation of the Darwin theory in the three
      beam case to tridiagonal block matrices are also presented.

PMID- 10927272
TI  - Molecular packing groups and ab initio crystal-structure prediction.
AB  - Ab initio crystal structure prediction can proceed by minimization of the packing
      energy of Z independent molecules per cell, or alternatively by energy
      minimization taking one molecule as independent and Z - 1 molecules as related by
      assumed space-group symmetry. In the former method, a large number of positional
      variables must be considered. In the latter method, a large number of space
      groups must be considered. An alternative, more efficient, procedure is proposed,
      where it is recognized that values of Z and the number of molecules in the
      asymmetric unit, Z', impose restrictions on possible space groups. Examples of
      application of this method to crystal structure prediction are given.

PMID- 10927273
TI  - Polysomatic series in the structures of complex cuprates.
AB  - The modular approach was applied to analyse the structure of complex cuprates.
      The modular series of various types were distinguished in the family of layered
      cuprates making use of the classification scheme in a fragment approximation
      developed earlier. The poly-somatic series were revealed in the groups of
      cuprates which were expected to possess the properties of both salt and oxide.
      The structure of the ladder-type cuprates was analysed in more detail. The
      present study has shown that the polysomatic model can be efficiently applied to
      the structural analysis of complex cuprates.

PMID- 10927274
TI  - Spectral decomposition of the linear elastic tensor for monoclinic symmetry.
AB  - The compliance fourth-rank tensor related to crystalline or other anisotropic
      media belonging to the monoclinic crystal system is spectrally decomposed for the
      first time, and its characteristic values and idempotent fourth-rank tensors are
      established. Further, it is proven that the idempotent tensors resolve the stress
      and strain second-rank tensors into eigentensors, thus giving rise to a
      decomposition of the total elastic strain-energy density into non-interacting
      strain-energy parts. Several examples of representative inorganic crystals of the
      monoclinic system illustrate the results of the theoretical analysis. It is also
      proven that the essential parameters required for a coordinate-invariant
      characterization of the elastic properties of a crystal exhibiting monoclinic
      symmetry are both the six characteristic values of the compliance tensor and
      seven dimensionless parameters. These material constants, referred to as the
      eigenangles, are shown to be accountable for the orientation of the stress and
      strain eigentensors, when represented in a stress coordinate system. Finally, the
      restrictions dictated by the classical thermodynamical argument on the elements
      of the compliance tensor, which are necessary and sufficient for the elastic
      strain-energy density to be positive definite, are investigated for the
      monoclinic symmetry.

PMID- 10927275
TI  - Modified form factors from multiconfiguration Dirac-Fock wave functions for
      neutral atoms with Z = 70-100.
AB  - Tables of modified X-ray scattering factors for neutral elements with Z = 70-100
      have been calculated using multiconfiguration Dirac-Fock wave functions. The
      physical approximation is a next step beyond the usual form-factor approximation
      in calculating elastic scattering photon intensities. Differences as large as 3
      6% compared to previous calculations of the same kind are obtained; differences
      from the usual form factors are much larger.

PMID- 10927276
TI  - Determination of mean inner potential of germanium using off-axis electron
      holography.
AB  - Off-axis electron holography has been used to determine the mean inner potential
      of germanium using cleaved 90 degrees wedge samples, where the wedge thickness
      profiles were checked by weak-beam dark-field extinction fringes. Dynamical
      contributions to the phase of the image were minimized by tilting to weakly
      diffracting conditions, as confirmed by reference to convergent-beam electron
      diffraction patterns. Small residual corrections were determined using multislice
      calculations. From a total of 18 separate measurements, it is concluded that the
      value of the mean inner potential is 14.3(2) V, which agrees with recent
      theoretical calculations to within experimental error.

PMID- 10927277
TI  - Periodic intensity distribution (PID) of mica polytypes: symbolism, structural
      model orientation and axial settings.
AB  - Following a preliminary revisitation of the nomenclatures in use for mica
      polytypes, the properties of the periodic intensity distribution (PID) function,
      which represents the Fourier transform of the stacking sequence, are analysed. On
      the basis of the relative rotations of neighbouring layers, mica polytypes are
      classified into three types; for each type, the PID exists in different subspaces
      of the reciprocal space. A revised procedure to compute the PID, in which further
      restrictions on the structural model orientation are introduced, is presented. A
      unifying terminology based upon the most common symbols used to describe mica
      polytypes (RTW, Z and TS) is derived; these symbols represent the geometrical
      basis for the computation of the PID. Results are presented for up to four layer
      polytypes and are compared with the reflection conditions derived by means of
      Zvyagin's functions. Both the PID values and the reflection conditions are
      expressed in suitable axial settings and compared with previous partial reports,
      revealing some errors in previous analyses. A computer program to compute PID
      from the stacking symbols is available.

PMID- 10927278
TI  - Dynamical calculation of crystal truncation rods for surfaces and interfaces
      using a Cartesian coordinate transformation technique.
AB  - A dynamical calculation scheme that employs Cartesian coordinates with a z axis
      normal to the crystal surface to define polarization unit vectors and wavefields
      is applied to interpret the intensity distribution of crystal truncation rods for
      surfaces and interfaces. A comparison between this calculation scheme and the
      asymptotic iteration approach using the conventional presentation of the
      polarization components of the wavefields, with the sigma and pi components
      perpendicular to the wavevectors, is presented. It is found that the use of
      Cartesian coordinate systems can provide correct boundary conditions in
      determining the wavefield amplitudes, thus leading to a rigorous and general
      calculation scheme for dynamical diffraction from surfaces and interfaces.

PMID- 10927279
TI  - Three-wave X-ray diffraction: an analysis scheme of the sensitivity in
      determining triplet phase invariants.
AB  - A model for analysing the phase sensitivity of the reflection coefficients of a
      diffracted wave in the case of three-wave X-ray diffraction is proposed. This
      model considers three-wave diffraction as the interference of the directly
      excited and the Umweg-excited diffracted waves and seems to account properly for
      the phase sensitivity as well as the behaviour of an involved diffracted wave as
      a function of the triplet phase invariant, the polarization state of the incident
      wave and the diffraction geometry. The practical issues for phase determination
      are also considered.

PMID- 10927280
TI  - Faster calculation of the full matrix for least-squares refinement.
AB  - Equations derived from a statistical model and valid for all space groups give
      estimates of the elements of the matrix for least-squares refinement of atomic
      coordinates and isotropic thermal parameters for a large crystal structure with
      many diffraction data. The elements are functions of the lengths and directions
      of Patterson vectors and the distribution of weights as a function of Bragg
      angle. For a large data set, this matrix, or a portion of it, can be calculated
      in a time that is approximately proportional to the number of elements calculated
      and independent of the number of reflections.

PMID- 10927281
TI  - The efficient calculation of the normal matrix in least-squares refinement of
      macromolecular structures.
AB  - The optimization procedure with the greatest power of convergence is the full
      matrix method. This method has not been utilized to a great extent in
      macromolecular refinement because of the great cost of both calculating and
      inverting the 'normal' matrix. This paper describes an algorithm that can
      calculate this matrix in a relatively short amount of computer time. The
      procedure requires two Fourier transforms, which can be performed with the fast
      Fourier transformation (FFT) algorithm, as well as a large number of simple
      function products.

PMID- 10927282
TI  - Room-temperature and low-temperature structure of Nd1-xCaxMnO3 (0.3 </= x </=
      0.5).
AB  - The structure of the insulating manganites Nd(1-x)Ca(x)MnO(3) (0.3 </= x </= 0.5)
      has been studied against temperature using electron diffraction and neutron
      diffraction. At room temperature, the three compounds with x = 0.3, 0.4 and 0.5
      exhibit the orthorhombic GdFeO(3)-type structure (a approximately 2(1/2)a(p), b
      approximately 2a(p), c approximately 2(1/2)a(p)). Below the charge-ordering
      temperature of approximately 250 K, a doubling of the lattice is observed along
      the a axis which could be interpreted as an ordering of the d(z(2)) Mn(3+)
      orbitals. The low-temperature polymorph has ortho-rhombic symmetry for x = 0.5
      and monoclinic symmetry for x = 0.4 and 0.3. The low-temperature structure of the
      x = 0.4 sample was refined using neutron diffraction data. The HREM study at room
      temperature confirms the average GdFeO(3)-type structure and indicates the
      existence of defective areas with a lower symmetry.

PMID- 10927283
TI  - A new type of constraint in the maximum-entropy method using ambiguous phase
      information from anomalous-scattering powder data.
AB  - Anomalous scattering of X-rays at a synchrotron source can be used for the ab
      initio structure determination of unknown crystal structures using only powder
      diffraction data. For noncentrosymmetric crystals, the phases of structure
      factors can only be determined with a remaining ambiguity, when one chemical
      element is used as resonant scatterer. A corresponding additional constraint
      function has been built into an enhanced version of the program MEED, so that now
      all types of information gained from an anomalous-scattering powder diffraction
      experiment can be used in a maximum-entropy calculation of the electron-density
      distribution: phased reflections, unphased reflections, intensities of groups of
      overlapping reflections, and now also reflections with a remaining ambiguity in
      the phase. This is important for practical use, since a lot of information is
      already lost in the powder diagram compared with single-crystal datasets and it
      is essential to use all remaining information. The new constraint is demonstrated
      with the structure of Cu(5)Zn(8).

PMID- 10927284
TI  - Molecular fragment electric moments derived from the fit of the experimental
      electrostatic potential. Application to the water molecule.
AB  - The electrostatic potential is a multicenter property that can be expressed as a
      sum of the contributions of electric moments located at each atomic site of a
      molecule. Independently of the model used to generate the electrostatic potential
      around the system, these atomic moments can be accurately obtained by the fit of
      this physical property outside the van der Waals envelop. However, the larger the
      system, the greater the number of parameters. In this study a way is proposed to
      reduce the number of centers in the representation of the electrostatic potential
      which becomes a sum of fragment contributions rather than atomic ones. A sample
      of six water molecules in different crystal environments was chosen to discuss
      the derived values of the electric moments referred to the molecular center of
      mass.

PMID- 10927285
TI  - A likelihood-based search for the macromolecular position in the crystalline unit
      cell.
AB  - The goal of this work is to analyse whether the generalized likelihood criterion
      can be used to find the best spherical envelope of a macromolecule in a unit
      cell. A family of spherical envelopes is ranged in accordance with their
      likelihood values calculated by means of a Monte Carlo-type computer procedure.
      Two kinds of envelope families were tested. The first one was composed of
      spherical envelopes of fixed radius but different positions in the unit cell. In
      the second case, the sphere radii were linked to their centre position so that
      the total volume occupied by all symmetry-related spheres was roughly equal to
      the total volume occupied by the real molecule. The experiments showed that when
      using the first type of envelope the level of the signal for the right solution
      is higher than the one obtained with the straightforward R-factor-based single
      Gaussian-atom search, but spurious maxima (usually placed on the symmetry axes)
      may still exist. The use of the second type of envelope family reduces the level
      of the spurious maxima.

PMID- 10927286
TI  - Quasiperiodic packings of fibres with icosahedral symmetry.
AB  - Different icosahedral packings of fibres have been experimentally realized. A
      packing construction with straight fibres of the same circular cross section,
      only parallel to fivefold icosahedral axes and respecting the closest packing
      condition, is reported. Its characteristics of point-group symmetry and related
      two-dimensional tilings are analysed. But for determining unambiguously all the
      fibre positions it appears that a mathematical construction has to be made from
      the cut and projection of a five-dimensional space. Through such a method, the
      volume fraction of fibrous reinforcement in a composite material can be
      calculated. The related two-dimensional tiling can be proved to be different from
      a Penrose tiling. Finally, the characteristics of other icosahedral packings
      where fibres are parallel to threefold axes or to both threefold and fivefold
      axes are briefly discussed and a few further experiments on their elasticity
      properties and photonic band-gap structure are suggested.

PMID- 10927287
TI  - Report of a Subcommittee on the Nomenclature of n-Dimensional Crystallography. I.
      Symbols for point-group transformations, families, systems and geometric crystal
      classes.
AB  - The notation of crystallography in arbitrary dimensions is considered.
      Recommended symbols for point-group transformations, geometric crystal classes,
      families and systems are presented.

PMID- 10927288
TI  - Reverse Monte Carlo modelling of neutron powder diffraction data.
AB  - A new reverse Monte Carlo (RMC) method for modelling both lattice and magnetic
      disorder in powder crystalline materials by direct calculation of the structure
      factor has been developed. The method, the program and the basic theory are
      described in some detail. Initial results from modelling the lattice and magnetic
      structure of MnO around the Neel temperature are also presented.

PMID- 10927289
TI  - Chirality and general aspects of symmetry.
AB  - The phenomenon of chirality is described in terms of symmetry and via symmetry
      operators.

PMID- 10927290
TI  - Structure of the alloy Ti50Ni48.7Co1.3.
AB  - The structure of the R phase of the alloy Ti(50)Ni(48.7)Co(1.3) was determined by
      the crystallogeometric analysis of martensitic transformations in titanium
      nickelide. This analysis is based on the concept of cooperative thermal
      vibrations of the (110)-like planes in the b.c.c. and B2 structures and their
      freezing (transformation to static displacements) at the point of the phase
      transition. The space group of the R phase is trigonal P31m with a hexagonal
      Bravais lattice. The validity of the R-phase structure determination is confirmed
      by an X-ray diffraction pattern that was obtained at room temperature using Cu
      Kalpha radiation. The Rietveld procedure was used to compare the calculated and
      experimental X-ray diffraction patterns. The proposed structural model of the R
      phase agrees satisfactorily with the experimental data.

PMID- 10927291
TI  - Structure characterization and predictability by Voronoi analysis.
AB  - The unique ability of tessellation methods to characterize atomic structures is
      highlighted, with the Voronoi tessellation, by virtue of its freedom from
      constraining assumptions, emphasized as pre-eminent among these methods. It is
      demonstrated how to extract information from an atomic structure by constructing
      its Voronoi tessellation and analysing the results. In so doing, insight is
      gained into the coordination patterns of the atoms and how their positions are
      influenced by neighbours. As an example of such a procedure, typical Voronoi
      volumes are calculated for 72 atom types found in a set of 249 binary
      intermetallic and ionic compounds. Whereas the various atom types have broadly
      characteristic volumes, these are also sensitive to the other atom types with
      which they are combined in a given compound, i.e. whether the latter behaves as a
      metal, semimetal, semiconductor or insulator. Further, smaller variations in
      volume occur for different atom types within these four categories. Thus,
      structural information obtained from the Voronoi tessellation may possibly be
      correlated directly with atomic properties.

PMID- 10927292
TI  - Electron-density-based calculations of intermolecular energy: case of urea.
AB  - The intermolecular interaction energy in crystalline urea has been calculated
      both from diffraction data and from the Hartree-Fock crystalline electron-density
      distribution, using a modified atom-atom approximation scheme. The electrostatic
      part of this energy has been calculated from the atomic multipole moments,
      obtained by adjustment of the multipole model to experimental X-ray and to
      theoretical Hartree-Fock structure amplitudes. To obtain the induction energy,
      multipole moments were calculated from structure amplitudes for the crystalline
      electron density and from those that refer to the electron density of a
      superposition of isolated molecules. This worked well for the calculation of the
      interaction energy from Hartree-Fock data (6% difference from the sublimation
      energy value), but not for the interaction energy from experimental data, where
      the moments of the superposition have to come from Hartree-Fock calculations: the
      two sets of multipole moments are far too different. The uncertainty of the
      phases of the structure amplitudes, combined with systematic errors in the
      theoretical data and noise in the experimental values, may account for the
      discrepancies. The nature of the different contributions to intermol-ecular
      interactions for urea is examined.

PMID- 10927293
TI  - The phase transitions and crystal structures of Ba3RM2O7.5 complex oxides (R =
      rare-earth elements, M = Al, Ga).
AB  - The structures of alpha-Ba(3)RAl(2)O(7.5) and beta-Ba(3)RM(2)O(7.5) complex
      oxides (R = rare-earth elements, M = Al, Ga) have been studied by a combination
      of X-ray diffraction, electron diffraction (ED) and high-resolution electron
      microscopy (HREM). The alpha and beta forms have cell parameters related to the
      perovskite subcell: a = 2a(per), b = a(per)(2)(1/2), c = 3a(per)(2)(1/2),
      however, the alpha form has an ortho-rhombic unit cell whereas the beta form
      adopts monoclinic symmetry. The crystal structure of monoclinic
      Ba(3)ErGa(2)O(7.5) was refined from X-ray powder data (space group P2/c, a =
      7.93617(9), b = 5.96390(7), c = 18.4416(2) A, beta = 91.325(1) degrees, R(I) =
      0.023, R(P) = 0.053), the structure of the alpha form (space group Cmc2(1)) was
      deduced from ED and HREM data. The important feature of the alpha and beta
      structures is the presence of slabs containing strings of vertex-sharing
      tetrahedral Al(2)O(7) pairs. Two almost equivalent oxygen positions within the
      strings can be occupied either in an ordered manner leading to the low
      temperature beta phase or randomly resulting in the high-temperature alpha
      structure. The critical temperature of this order-disorder phase transition was
      determined by high-temperature X-ray diffraction and by differential thermal
      analysis (DTA). In situ ED and HREM observations of the second-order phase
      transition confirmed the symmetry changes and revealed numerous defects (twins
      and antiphase boundaries) formed during the phase transformation.

PMID- 10927294
TI  - X-ray diffraction in perfect t x l crystals. Rocking curves.
AB  - A general formalism, based on the Takagi-Taupin equations, for calculating
      rocking curves in perfect t x l crystals is presented. It includes nonsymmetrical
      scattering, refraction, and ordinary and anomalous absorption. t and l may be
      varied independently. In the limit of a semi-infinite crystal, the standard
      results from the fundamental theory are retrieved. For crystal dimensions less
      than the extinction length, the theory converges to the kinematical limit.
      Simulations for germanium and silicon show significant influence of crystal
      finiteness. When dynamical effects are prominent, the curves exhibit various
      degrees of asymmetry and the full width at half-maximum is generally larger than
      the corresponding Darwin width. This is attributed to combined Laue and Bragg
      contributions which are shifted with respect to each other owing to refraction.

PMID- 10927295
TI  - Diffraction of 100 to 200 keV X-rays from an Si1-xGex gradient crystal:
      comparison with results from dynamical theory.
AB  - In a large Czochralski-grown Si(1-x)Ge(x) (0.02 </= x </= 0.07) gradient crystal,
      diffraction patterns have been measured in symmetrical Laue geometry using
      synchrotron radiation in the energy range 100-200 keV. The experimental data are
      in very good agreement with the results from geometrical optics theory for
      distorted crystals, if the creation of new wavefields for strain gradients larger
      than a critical value is taken into account. In this sense, the crystal behaves
      like an ideal gradient crystal. If the normal absorption is disregarded, for
      reflection 111 and 100 keV energy, the full width at half-maximum values and the
      peak reflectivities of the diffraction patterns range from 14.6" and 97%,
      respectively, to 70.9" and 74%, respectively, for a variation in the Ge
      concentration from 3.5 to 5.3 at.%.

PMID- 10927296
TI  - Wavelength-modulated diffraction: a new method for phase determination.
AB  - A new diffraction method has been developed in which the intensity of Bragg
      reflections is measured while changing continually the wavelength of the
      radiation over a range in the vicinity of the absorption edge of an atom
      contained in the crystal. It is shown that the intensity gradient with respect to
      the wavelength of the hkl reflection is in a simple relation to the real and
      imaginary parts of the structure factor of that reflection and, if the positions
      of the anomalously scattering atoms are known or properly assumed, the phase of
      F(hkl) can be derived by solving simultaneous linear equations. The procedure is
      particularly simple when the crystal is centrosymmetric. The method, called the
      wavelength-modulated diffraction (WMD) method, is free from the problem of
      intensity scaling encountered in other methods of phase determination.
      Synchrotron radiation is most suited to WMD measurements. Suggestions on how to
      measure the intensity gradient are given and the possible errors involved are
      discussed.

PMID- 10927297
TI  - Reduced projection operators and algebraic expressions for the symmetry-adapted
      functions of the icosahedral group.
AB  - The algebraic expressions for the reduced projection operators rho((lambda){?bar
      u})(u) = summation operator(i=1)(4) u(i) ?hat{beta(i)} for the irreducible
      representation (irrep) lambda of the icosahedral group I are found by using the
      double-induced technique and eigenfunction method, where ?hat{beta(i)} are the
      double-coset generators of I with respect to the cyclic subgroup C(5). Simple
      algebraic expressions are derived for the symmetry-adapted functions (SAF's) by
      applying the reduced projection operators rho((lambda){?bar u})(u) to Y(l {?bar
      m}). The SAF's are functions of the angular momentum l, the quantum numbers
      lambda, u of the group chain I superset C(5) and the multiplicity label ?bar m.
      In this way, the SAF problem of the group I is solved once for all instead of for
      one angular momentum l each time.

PMID- 10927298
TI  - Tensor distinction of domain pairs in ferroic crystals.
AB  - A classification of domain pairs in ferroic crystals is given in which all domain
      pairs in each class can be distinguished by the same set of physical property
      tensors. Tabulations are presented giving in which ferroic phase transitions such
      domain pairs arise. Whether a physical property tensor can or cannot distinguish
      between the domains of domain pairs of each class is given for a wide variety of
      physical properties. This material is based on work supported by the National
      Science Foundation under grant No. DMR-9722799.

PMID- 10927299
TI  - Dynamical scattering and electron diffraction from thin polymer lamellar crystals
      - poly(tert-butylethylene sulfide).
AB  - Strong violations of Friedel symmetry are observed in hk0 electron diffraction
      patterns from lamellar crystals of poly(tert-butylethylene sulfide) obtained at
      120 kV. These deviations are largely explained by a multislice dynamical
      scattering calculation based on the crystal structure model. Further improvement
      is found when a secondary scattering component is added, in keeping with a
      perfect crystallite thickness less than that of the lamellar thickness. Despite
      the multiple-scattering perturbations, the frustrated chain packing can still be
      determined by direct methods followed by Fourier refinement. However, the Friedel
      related intensities must be averaged before calculation of normalized structure
      factors.

PMID- 10927300
TI  - Absolute structure and absolute configuration.
AB  - Fundamental notions concerning absolute structure and absolute configuration, and
      their determination from single-crystal diffraction measurements, are presented
      and reviewed. A glossary of terms with definitions useful in this field is
      provided. For absolute structure and its determination, the separate but
      interacting influences of the structure and the inversion-distinguishing power of
      an X-ray diffraction experiment with dispersive scatterers are examined.
      Important experimental and algorithmic details of the current methods used for
      absolute-structure determination are provided. Characterization of crystals for
      absolute-structure determination and of molecules for absolute-configuration
      determination are treated. Attention is given to the analysis of absolute
      structure and absolute configuration in twinned crystals.

PMID- 10927301
TI  - Seminvariant density decomposition and connectivity analysis and their
      application to very low resolution macromolecular phasing.
AB  - A low-resolution Fourier synthesis is thought to show a molecule as a compact
      region of a high electron density. As a consequence, the number of such regions,
      chosen at a proper cut-off level, should be equal to the number of molecules in
      the unit cell. This hypothesis may be used as a basis for selection criteria in
      multisolution ab initio phasing procedures. However, when working with a small
      number of reflections, this hypothesis may break down. The suggested Fourier
      synthesis decomposition explains some reasons for failure and provides a
      connectivity-based procedure for the determination of macromolecular position in
      the crystal unit cell and the phasing of several low-resolution reflections. The
      simplest decomposition consists in separating the reflections into two sets
      according to whether their phases do or do not depend on a permitted origin
      shift. It is shown that the partial Fourier syntheses corresponding to these
      subsets are simply a half-sum and a half-difference of the initial electron
      density distribution with its shifted copy. Therefore, they display the true
      images overlapped with the shifted ones (or with shifted and additionally flipped
      copies for the latter synthesis). The paper generalizes the decomposition for the
      case of a finite subgroup of the group of permitted origin shifts and reveals the
      role of one-phase sem-invariants.

PMID- 10927302
TI  - Parameterization of the temperature dependence of the Debye-Waller factors.
AB  - Parameterization has been made for the temperature dependence of the Debye-Waller
      factors of 68 elemental crystals and 17 compounds with the zinc-blende structure.
      The Debye-Waller factors of 46 elemental crystals were calculated based on the
      available phonon density of states, and those of the remaining 22 elemental
      crystals were estimated using the Debye approximation for the phonon density of
      states. The Debye-Waller factors of the zinc-blende compounds were obtained from
      the 14-parameter shell-model calculations of Reid [Acta Cryst. (1983), A39, 1
      13].

PMID- 10927303
TI  - Quantitative phase determination for macromolecular crystals using stereoscopic
      multibeam imaging.
AB  - Without invoking anomalous dispersion and heavy-atom derivatives, it is
      demonstrated that it is possible to directly determine the phases of a large
      number of reflections collected in a short time from macromolecular crystals
      using a stereoscopic oscillation-crystal imaging technique, in a multibeam
      diffraction geometry, where two crystallographic axes in opposite directions are
      employed as the rotation axes. The intensity profiles (distributions) of the
      diffraction spots versus the varying tilt Bragg angle of the rotation axis in the
      two stereoscopically related images yield quantitative phase information. Many
      multiple diffraction profiles of tetragonal lysozyme and an unknown protein
      structure are obtained at the rate of 100 profiles per 30 min of X-ray exposure.

PMID- 10927304
TI  - Refinement of crystal structural parameters using two-dimensional energy-filtered
      CBED patterns.
AB  - A new method to refine crystal structural parameters using convergent-beam
      electron diffraction (CBED), which is applicable to nanometre-size crystal
      structure analysis, is proposed. This method is based on the fitting between
      theoretical calculations and experimental intensities of energy-filtered two
      dimensional CBED patterns containing higher-order Laue-zone (HOLZ) reflections.
      The use of HOLZ reflections is essential for the method because small
      displacements of atoms can be sensitively detected using HOLZ reflections with
      large reciprocal vectors. For this purpose, a new Omega-filter transmission
      microscope (JEM-2010FEF), which can take energy-filtered CBED patterns up to a
      high angle with a small distortion, and a new analysis program to refine
      structural parameters, which is based on many-beam Bloch-wave calculations and
      nonlinear least-squares fitting, have been developed. As a test example, a
      positional parameter and isotropic and anisotropic Debye-Waller factors of CdS
      have been refined. Two-dimensional CBED patterns calculated with the refined
      parameters show very good agreement with the experimental ones, and the refined
      values of the parameters also agree well with the result of a single-crystal X
      ray diffraction experiment. Important problems of the analysis procedure are
      discussed item by item.

PMID- 10927305
TI  - Tunable X-ray polarization reflector with perfect crystals.
AB  - The possibility of a transmission-type X-ray linear polarizer is investigated
      using a thin Bragg reflector as a polarizing filter. In this device, the
      transmitted beam (rather than the Bragg-reflected beam) is the useful output of
      the device. Consequently, the position and the direction of the transmitted beam
      are unchanged as the energy is changed, or even when the polarization direction
      to be filtered out is changed. Theoretical considerations as well as preliminary
      transmissivity measurements are presented. The use of perfect crystals of silicon
      and diamond is examined. A polarization ratio, defined as I(H)/I(V), higher than
      10(5) was observed in experiments to measure the performance characteristics of
      the proposed X-ray polarizing reflector. The transmission-type X-ray linear
      polarizer is well suited for spectroscopic measurements with polarized X-rays.

PMID- 10927306
TI  - Magnetic subperiodic groups.
AB  - The magnetic subperiodic groups, the 31 magnetic frieze-group types, the 394
      magnetic rod-group types and the 528 magnetic layer-group types, are derived and
      given symbols based on the symbols for the nonmagnetic subperiodic groups in
      Volume E of International Tables for Crystallography. The symbols are constructed
      in analogy to the Opechowski-Guccione symbols for magnetic space groups. Tables
      are given that list one group from each type. Each group is specified not only by
      its symbol but also by explicitly listing the coset representatives of the coset
      decomposition of the group with respect to its translational subgroup.

PMID- 10927307
TI  - On the errors in molecular dipole moments derived from accurate diffraction data.
AB  - The error in the molecular dipole moment as derived from accurate X-ray
      diffraction data is shown to be origin dependent in the general case. It is
      independent of the choice of origin if an electroneutrality constraint is
      introduced, even when additional constraints are applied to the monopole
      populations. If a constraint is not applied to individual moieties, as is
      appropriate for multicomponent crystals or crystals containing molecular ions,
      the geometric center of the entity considered is a suitable choice of origin for
      the error treatment.

PMID- 10927314
TI  - Indexing approximants of icosahedral quasicrystals.
AB  - It is well known that the crystallography of approxi-mants is directly related to
      that of the parent quasicrystal, once its unit-cell vectors are identified as
      parallel projections of certain N-dimensional lattice nodes A(i). Derived here
      are explicit simple relations for calculating the shear matrices varepsilon and
      the related crystallographic properties of the corresponding approximants,
      including diffraction indexing and the determination of the lattice in
      perpendicular space. Applied to low-dimensional approximants, the derivation
      shows that the systematic 'accidental' extinction rules observed in the
      pentagonal phases are generic extinctions that are due to the geometrical
      properties of the projected 1D lattice and are independent of the actual model of
      the quasicrystal.

PMID- 10927315
TI  - The joint probability distribution function of structure factors with rational
      indices. VI. Cases with reduced dimensionality.
AB  - The probabilistic formulas relating standard and mixed type reflections (these
      last show integral and half-integral indices) are derived. It is shown that
      probabilistic estimates can be obtained by using particular sections of the three
      dimensional reciprocal space. The concept of structure invariant is extended to
      define the wider class of structure quasi-invariant. Their statistical behaviour
      is briefly discussed with the help of some practical tests.

PMID- 10927316
TI  - SIR99, a program for the automatic solution of small and large crystal
      structures.
AB  - The moduli and flow diagram of the program SIR99 are described. New phasing
      algorithms are proposed working both in direct and in reciprocal space. Their
      cooperative work is able to solve the structures of both small and large
      molecules. In particular, small proteins can be solved ab initio without any use
      of prior information and any user intervention. The efficiency of the various
      algorithms employed by SIR99 has been tested, and the role of the tangent formula
      clarified. The user is also provided with some practical information concerning
      the computer power needed.

PMID- 10927317
TI  - X-ray intensity patterns from finite perfect crystals.
AB  - A theoretical study dealing with intensity interference patterns from the exit
      surfaces of finite perfect t x l crystals has been undertaken using the Takagi
      Taupin equations and the Riemann-Green technique. Nu-meri-cal simulations have
      been performed for the 220 reflection in diamond allowing for different types of
      amplitude-modulated incoming plane waves. The effects caused by limiting the
      waves by a slit system are also discussed. The results show strong influence of
      the lateral crystal boundaries and are closely related to the geometrical region
      structures formed by the characteristic lines associated with the equations. In
      the limit of a semi-infinite crystal, the Borrmann-Lehmann interference patterns
      are retrieved.

PMID- 10927318
TI  - Lattice dynamics and Debye-Waller factors of some compounds with the sodium
      chloride structure.
AB  - The lattice dynamics of 19 compounds with the sodium chloride structure have been
      investigated using shell models. The models are compared with existing
      experimentally measured phonon-dispersion curves and refined using a
      multidimensional downhill simplex method. Debye-Waller factors for these
      compounds are calculated over the temperature range from 1 to 1000 K where
      appropriate and the results are fitted analytically using polynomial regression.
      The results are compared with experimentally measured room-temperature Debye
      Waller factors and for most of the compounds the agreement is found to be better
      than 10%. At lower temperatures, it is expected that these results would be more
      accurate, since the harmonic approximation, which is crucial to the calculation
      of the Debye-Waller factors, works better. In choosing the models for particular
      applications, it is recommended that the model with the smallest standard error
      sigma is used for fitting the experimentally measured phonon-dispersion curves,
      or the model that shows best agreement with reliable experimental measurements of
      more relevant physical quantities, such as Debye-Waller factors in
      crystallography.

PMID- 10927319
TI  - Anisotropic dispersion of the band structure and formation of ring patterns in
      CBED.
AB  - An off-axis ring pattern was observed in the <1-11> zone-axis CBED pattern of an
      NiO single crystal. The pattern was interpreted as resulting from anisotropic
      dispersion of the band structure of the two most strongly excited free Bloch
      waves and strong absorption of the most tightly bound 1s Bloch state. Comparison
      has also been made with the case of MgO which has the same structure as NiO but
      weaker scattering power. The tightly bound 1s Bloch state in MgO was found to
      play an important role together with a strongly excited free Bloch state and a
      more conventional zone-axis ring pattern similar to that observed in the <001>
      zone-axis CBED pattern of silicon was observed.

PMID- 10927320
TI  - Experimental determination of electric-field-induced differences in structure
      factor phases of the order of 2%
AB  - In order to understand the induced electron-density response of covalently bonded
      materials to an externally applied electric field, the change of structure-factor
      phases of several weak reflections of GaAs has been measured by three-beam
      interferences. Using a modulation technique, phase variations of the order of 1
      degrees for a field strength of 1 kV mm(-1) were determined. Although the
      statistics of these first experiments are rather poor, the experiment verifies
      qualitatively the predictions of a semi-empirical bond-charge model. The measured
      phase variation is the smallest value determined up to now.

PMID- 10927321
TI  - Electron density in ammonium dihydrogen phosphate: non-uniqueness of the
      multipolar model in simple inorganic structures.
AB  - X-ray and neutron diffraction data of a single crystal of ammonium dihydrogen
      phosphate have been used for the determination of the electron density using
      multipolar expansion of the density around each nucleus. As the ammonium group
      was found to be nearly neutral from unconstrained multipole refinement,
      constrained refinements have been performed with the charge of the ammonium group
      ranging from zero to one. On the other hand, the expansion of the radial
      functions of the phosphorus atom was varied. All refinements led to almost the
      same agreement factors and residual densities. The consequences of such
      uncertainties on the topology of the electron density are discussed, namely the
      topology of the P-O bond critical point.

PMID- 10927322
TI  - Algebraic expressions for symmetry-adapted functions of the icosahedral group in
      spinor space.
AB  - Algebraic expressions for projection operators and symmetry-adapted functions
      (SAFs) of the icosahedral group for spinor (double-valued) representations are
      found by using the double-induced technique and eigenfunction method. The SAFs
      are functions of the angular momentum j, the quantum numbers lambda, nu, u of the
      group chain I superset D(5) superset C(5), and the multiplicity label {?bar m}.
      By this procedure, SAFs for the group I are provided once for all instead of one
      j value at a time.

PMID- 10927323
TI  - Dynamical scattering and electron diffraction from thin polymer lamellar crystals
      - poly(tert-butylethylene sulfide). Erratum.
AB  - In the paper by Dorset et al. [Acta Cryst. (1999), A55, 901-907], the last line
      of page 904 should read 'ellipsisthe S atoms. However, the autocorrelation
      functionellipsis'.

PMID- 10927325
TI  - Prices of IUCr journals.

PMID- 10927326
TI  - Structural Science enters the electronic era.

PMID- 10927327
TI  - Graph-set analysis of hydrogen-bond patterns: some mathematical concepts.
      Erratum.
AB  - Owing to a serious printing error, this article [Grell et al. (1999). Acta Cryst.
      B55, 1030-1043] was printed incorrectly. Pages 1029-1044 have thus been reprinted
      and included as a loose insert with this issue of the journal.

PMID- 10927329
TI  - Structure and thermal behavior of the new superprotonic conductor
      Cs2(HSO4)(H2PO4). Erratum.
AB  - Table 2 in the paper by Chisholm & Haile [(1999), Acta Cryst. B55, 937-946] was
      printed incorrectly. The correct version is presented, including H-atom
      coordinates.

PMID- 10927332
TI  - Synchrotron X-ray study of the electron density in RFeO3 (R = Nd, Dy).
AB  - Structure factors for small hydrothermally grown orthorhombic neodymium and
      dysprosium iron oxides RFeO(3) (R = Nd, Dy) were measured with focused lambda =
      0.84 A synchrotron radiation using a fast avalanche photodiode (APD) counter.
      Higher symmetry in the deformation electron density (Deltarho) maps reflects the
      coordination of the magnetic atoms in the structure and implies that Deltarho is
      sensitive to the cation-cation magnetic interactions. Within a given compound the
      local Deltarho topographies around the R and Fe atoms are similar, but differ
      markedly between compounds. The difference in Deltarho near the Nd and Dy atoms
      is associated with the different type of spin reorientation transitions in these
      compounds. The R-Fe magnetic interactions determine the magnetic phase
      transitions and consequently affect the electron distribution. Synchrotron
      radiation diffraction imaging of the electron density provides an additional tool
      for probing the magnetic properties of materials.

PMID- 10927333
TI  - Temperature-dependent neutron powder diffraction evidence for splitting of the
      cationic sites in ferroelectric PbHf0.4Ti0.6O3.
AB  - Temperature-dependent neutron powder diffraction experiments (diffractometer 3T2
      LLB, Saclay, France, lambda = 1.227 A) have been performed on the perovskite-like
      lead hafnate titanate PbHf(0.4)Ti(0.6)O(3). This compound belongs to the solid
      solution denoted PHT, which derives from the well known ferroelectric PZT series.
      It exhibits a ferroelectric-to-paraelectric phase transition around 620 K,
      between the low-temperature tetragonal phase and the high-temperature cubic
      phase. The tetragonal structure of the ferroelectric phase has been refined at 10
      and 300 K using a Rietveld-type method: space group P4mm with Z = 1; a(t) = 3.999
      (1), c(t) = 4.120 (1) A, c/a = 1.030, V = 65.89 A(3) at 10 K; a(t) = 4.012 (1)
      and c(t) = 4.100 (1) A, c/a = 1.022, V = 65.99 A(3) at 300 K. The cubic structure
      of the paraelectric phase has also been refined at 720 K: space group Pm3;m, Z =
      1, a(c) = 4.046 (1) A, V = 66.23 A(3). Cation displacements and oxygen-octahedra
      elongations have been observed as a function of temperature. Evidence for
      peculiar behaviour associated with the relative shifts of the Hf and Ti atoms
      (thought until now to be on the same crystallographic site) was found through an
      anomaly of the mean-square atomic displacements of the Hf/Ti pseudo-nucleus. The
      PDF Nos for PbHf(0.4)Ti(0.6)O(3) are 48-49-9 and 48-49-10.

PMID- 10927334
TI  - Neutron structures of ammonium tetrafluoroberyllate.
AB  - It is thought that hydrogen bonding is responsible for the ferroelectricity in
      ammonium tetrafluoroberyllate, (NH(4))(2)BeF(4). In the past X-ray data have been
      collected, but these did not permit accurate determination of the H-atom
      positions. In order to obtain more accurate information the neutron structures
      have now been determined for the paraelectric and ferroelectric phases. Going
      from the paraelectric to the ferroelectric phase, both the BeF(4)(2-) and the
      NH(4)(+) ions rotate and shift from the mirror planes of the paraelectric phase.
      This results in removal of the mirror-plane symmetry and formation of a
      superlattice with the a axis doubled. Along the polar c axis, the NH(4)(+) ions
      move towards the BeF(4)(2-) ions within chains of molecules and the chains move
      slightly relative to one another. The rotations and translations give rise to
      stronger hydrogen-bonding interactions.

PMID- 10927335
TI  - High-temperature phases of NaNbO3 and NaTaO3.
AB  - The high-temperature phases of the perovskites sodium niobate, NaNbO(3), and
      sodium tantalate, NaTaO(3), have been re-examined using the high-resolution
      powder diffractometer HRPD at the ISIS neutron spallation source; the two
      materials show the same sequence of phases with tilted octahedra. Diffraction
      patterns were measured every 5 K allowing structural changes with temperature
      within a single phase to be determined for the first time. Previous structure
      determinations within one phase had been performed at a single temperature only.
      The octahedra are tilted about pseudocubic <100> directions and are also
      deformed; the magnitude of the deformation is shown to be proportional to the
      square of the angle of tilt as expected from a phenomenological theory applied to
      such transitions. The structures of NaNbO(3) between 753 and 793 K and of
      NaTaO(3) below 758 K are not as reported in the literature.

PMID- 10927336
TI  - Residual short-range order in the heavy fermion compound CeInCu2.
AB  - By using the X-ray diffraction technique, residual short-range order was detected
      in CeInCu(2), cerium dicopper indium, which is known to be a heavy fermion
      compound. In spite of the long-range order of this substance, diffuse scattering
      exhibiting short-range order was observed at room temperature. The correlation
      parameters obtained showed that an incorrectly occupied lattice site has a
      tendency to gather atoms of different species at the neighboring sites along the
      <111> directions. Thus, the disordered region would form a cluster composed of
      several disordered atoms. Furthermore, a chain-type correlation which has a
      period of 20-23 A along the same directions was indicated. The superstructure
      like feature of the disordered atoms hardly increases the residual resistivity.
      It is consistent with the behavior of the residual resistivity under high
      pressure.

PMID- 10927337
TI  - Disorder determined by high-resolution powder diffraction: structure of
      pentamethylcyclopentadienyllithium.
AB  - The crystal structure of pentamethylcyclopentadienyllithium, [Li(C(10)H(15))]
      (LiCp*), has been determined from a high-resolution powder pattern by modelling
      and the maximum entropy method (MEM). The compound crystallizes in space group
      R3m with lattice parameters a = b = 14.7711 (5), c = 3.82206 (6) A and V = 722.19
      (4) A(3) (Z = 3). LiCp* forms polymeric 'multidecker' chains along the c axis.
      The pentamethylcyclopentadienyl anions are coplanar with each other and show
      threefold rotational disorder. The MEM calculations did not only confirm the
      structural model and the type of disorder, but also discovered additional
      symmetry compared with the Rietveld analysis. This is the first solid-state
      structure of a Lewis-base-free alkali metal Cp* compound.

PMID- 10927338
TI  - Electron density study of urea using TDS-corrected X-ray diffraction data:
      quantitative comparison of experimental and theoretical results.
AB  - The electron-density distribution in urea, CO(NH(2))(2), was studied by high
      precision single-crystal X-ray diffraction analysis at 148 (1) K. An experimental
      correction for TDS was applied to the X-ray intensities. R(merge)(F(2)) = 0.015.
      The displacement parameters agree quite well with results from neutron
      diffraction. The deformation density was obtained by refinement of 145 unique low
      order reflections with the Hansen & Coppens [Acta Cryst. (1978), A34, 909-921]
      multipole model, resulting in R = 0.008, wR = 0.011 and S = 1.09. Orbital
      calculations were carried out applying different potentials to account for
      correlation and exchange: Hartree-Fock (HF), density-functional theory/local
      density approximation (DFT/LDA) and density-functional theory/generalized
      gradient approximation (DFT/GGA). Extensive comparisons of the deformation
      densities and structure factors were made between the results of the various
      calculations and the outcome of the refinement. The agreement between the
      experimental and theoretical results is excellent, judged by the deformation
      density and the structure factors [wR(HF) = 0.023, wR(DFT) = 0.019] and fair with
      respect to the results of a topological analysis. Density-functional calculations
      seem to yield slightly better results than Hartree-Fock calculations.

PMID- 10927339
TI  - Crystal and molecular structures of diazapyrenes and a study of pi?cdotspi
      interactions.
AB  - Two diazapyrenes, 5,10-dimethyl-4,9-diazapyrene (1) and novel 2,7-dimethyl-4,9
      diazapyrene (2) have been synthesized. Their crystal structures are reported here
      and are the first representatives of diazapyrenes. Crystal data: (1) monoclinic,
      P2(1)/c, a = 4.0246 (5), b = 15.5147 (5), c = 9.1453 (9) A, beta = 101.23 (1)
      degrees, V = 560.1 (1) A(3), Z = 2, R = 0.043; (2) monoclinic, C2/m, a = 12.4968
      (3), b = 11.4751 (4), c = 3.9615 (5) A, beta = 96.80 (1) degrees, V = 564.09 (5)
      A(3), Z = 2, R = 0.0405. The experimental bond lengths are compared with those
      calculated by molecular mechanics (MM3), semi-empirical methods (MOPAC6.0-PM3,
      AM1, MNDO) and values predicted by valence-bond and variable-electronegativity
      self-consistent field (VESCF) methods. pi.pi interactions in (1), (2) and
      seventeen other pyrene and pyrene-like molecules selected from the Cambridge
      Structural Database [Allen & Kennard (1993). Chem. Des. Autom. News, 8, 131-137]
      have been studied. The following quantitative parameters of pi.pi interactions
      have been calculated: the shortest crystallographic axis, the offset parameter,
      the interplanar angle, the interactive volume and the overlapping surfaces. They
      are used for the classification of crystal-packing motifs; a high predominance of
      beta and a few cases of gamma and sandwich-herringbone types are observed. In
      addition, electronegativity, the sum of partial atomic charges of the ring non-H
      atoms and the number of aromatic skeleton electrons are used as parameters for
      classification. MOPAC-PM3 was used to calculate the partial atomic charges in
      (1), (2) and pyrene analogues. Correlations between geometrical and electronic
      structure parameters reveal an analogy between the beta-type structures and the
      crystal structure of graphite.

PMID- 10927340
TI  - Low-temperature crystallization and structure determination of N
      (trifluoromethyl)formamide, N-(2,2,2-trifluoroethyl)formamide and 2,2,2
      trifluoroethyl isocyanide.
AB  - Crystals of N-(trifluoromethyl)formamide, C(2)H(2)F(3)NO, (I), N-(2,2,2
      trifluoroethyl)formamide, C(3)H(4)F(3)NO, (II), and 2,2,2-trifluoroethyl
      isocyanide, C(3)H(2)F(3)N, (III), were grown in situ on an X-ray diffractometer
      and analysed by single-crystal X-ray diffraction methods at low temperatures.
      Crystal data: (I) orthorhombic, P2(1)2(1)2(1), a = 4.547 (2) A, b = 5.947 (3) A,
      c = 14.731 (9) A, V = 398.3 (4) A(3), Z = 4, M(r) = 113.05, T = 143 K, D(x) =
      1.885 Mg m(-3); (II) monoclinic, P2(1)/n, a = 4.807 (1) A, b = 16.707 (3) A, c =
      6.708 (1) A, beta = 109.90 (1) degrees, V = 506.6 (2) A(3), Z = 4, M(r) = 127.07,
      T = 141 K, D(x) = 1.666 Mg m(-3); (III) orthorhombic, P2(1)2(1)2(1), a = 5.668
      (2) A, b = 9.266 (3) A, c = 8.626 (2) A, V = 453.0 (2) A(3), Z = 4, M(r) =
      109.06, T = 163 K, D(x) = 1.599 Mg m(-3). The results showed that in the crystal
      both formamides (I) and (II) are exclusively present in the form of the Z isomer,
      although measurements of solutions of (I) have shown that the E isomer prevails
      [Lentz et al. (1987). Angew. Chem. 99, 951-953]. In addition ab initio
      calculations for (I) predicted the E isomer to be the more stable one. In
      compound (III) the isocyanide group is staggered with respect to the
      trifluoroethyl group. In the crystal packing of (I) and (II) intermolecular N-H.O
      hydrogen bonds generate infinite chains. In (I), these chains are linked to form
      sheets by C-H.O contacts. In the crystal structure of (III) each isocyanide
      dipole is surrounded by four electronegative F atoms with intermolecular C.F
      contacts between 3.4 and 3.5 A.

PMID- 10927341
TI  - Experimental charge density and electrostatic potential in nicotinamide.
AB  - The accurate crystal structure of nicotinamide, 3-pyridinecarboxamide, was
      determined from X-ray and neutron diffraction experiments: C(6)H(6)N(2)O, M(r) =
      122.13, monoclinic, P2(1)/c, Z = 4. The electron distribution at 150 K was
      determined by the maximum entropy method and the electrostatic potential in the
      crystal was calculated by Fourier convolution of the electron distribution. The
      electrostatic properties of the nicotinamide molecule depend on the molecular
      conformation. The asymmetric electrostatic potential field observed above and
      below the pyridine-ring plane is related to the rotation of the carboxamide group
      with respect to the pyridine plane. The positive potential peak at the C4 atom of
      the pyridine ring extends to the C=O-group side of the plane. The asymmetry of
      the potential on the C4 atom is consistent with the stereospecificity of hydride
      transfer in NAD(+)/NADH oxidoreduction.

PMID- 10927342
TI  - Structures of 2,6-disubstituted naphthalenes.
AB  - The crystal structures of 2,6-naphthalenedicarboxylic acid (NDA) and dimethyl 2,6
      naphthalenedicarboxylate (NDC) have been solved ab initio using a combination of
      X-ray powder diffraction and computational chemistry techniques. These two
      crystal structures, and that of 2,6-dimethylnaphthalene (DMN), have been refined
      by the Rietveld technique. DMN crystallizes in the orthorhombic space group Pbca,
      with a = 7.4544 (4), b = 6.0826 (6), c = 20.0946 (12) A, V = 911.1 (1) A(3) and Z
      = 4. The structure consists of a herringbone stacking parallel to a, resulting in
      loosely bound layers perpendicular to c. NDA crystallizes in the triclinic space
      group P1;, with a = 3.7061 (8), b = 7.4688 (14), c = 8.5352 (22) A, alpha = 86.62
      (2), beta = 85.49 (2), gamma = 87.99 (2) degrees, V = 235.00 (6) A(3) and Z = 1.
      The structure consists of loosely packed hydrogen-bonded chains along [11;1]. NDC
      crystallizes in the monoclinic space group P2(1)/c, with a = 13.41931 (14), b =
      6.14869 (5), c = 7.15257 (5) A, beta = 100.400 (1) degrees, V = 580.47 (1) A(3)
      at 300 K and Z = 2. The structure consists of layers of NDC molecules
      perpendicular to a. The ester group is twisted 20 degrees out of the mean ring
      plane in NDC. The conformations of the carboxyl groups in NDA and NDC differ. MP2
      calculations suggest that the observed twist in NDC corresponds to an increase in
      conformational energy of 9 kJ mol(-1).

PMID- 10927343
TI  - Three conformational polymorphs and order-disorder phase transition in a calix
AB  - Three polymorphs of a calix[4]arene fixed in the 1,3-alternate conformation by
      two bridges, a crown-6 on one side and a crown-6 including a photoisomerizable
      azobenzene unit on the other, 8,11,14,28,31,34,37,40,43,57,60,63-dodecaoxa-2,3
      diazanonacyclo[62.2.2.2(4,7).1(16,45).1(26,55).0(15,20).0(22,27).0(44,49).0(51,56
      ]doheptaconta-1(66),2,4,6,15,17,19,22,24,26,44,46,48,51,53,55,64,67,69
      nonadecene, have been characterized by single-crystal X-ray diffraction. In all
      the polymorphs the azobenzene group is in the more stable trans conformation. The
      polymorphism arises from the high conformational flexibility of the bridges,
      which are arranged differently and are highly disordered in the two monoclinic
      forms (1) and (2a). Form (2a) presents a phase transition near 268 (2) K, leading
      to a triclinic form (2b), differing from the high-temperature form by some
      ordering of the chains and a subsequent reduction in crystallographic site
      multiplicity. The evolution of the cell parameters and peak width with
      temperature has been investigated down to 173 (2) K. Adiabatic calorimetry
      measurements indicate a smooth transition centered at 265.0 (1) K, with a heat
      capacity jump of 60 mJ g(-1) K(-1), suggesting a second-order nature for the
      transition.

PMID- 10927344
TI  - Symmetry, pseudosymmetry and packing disorder in the alcohol solvates of L-leucyl
      L-valine.
AB  - The dipeptide L-Leu-L-Val can crystallize as a hydrate in the hexagonal space
      group P6(5) [Gorbitz & Gundersen (1996). Acta Chem. Scand. 50, 537-543], but
      forms 1:1 solvates when methanol, ethanol and 2-propanol are used as
      precipitating agents. The structures of these complexes can be divided into
      hydrophobic and hydrophilic layers. The alcohol molecules are embedded in the
      hydrophobic layers, but with the hydroxyl groups as crucial parts of the hydrogen
      bonding network. L-Leucyl-L-valine-methanol (1/1) crystallizes in the space group
      P2(1) with Z = 2. L-Leucyl-L-valine-ethanol (1/1) has very special systematic
      absences, and the structure could not be solved with direct methods. Unraveling
      the actual build-up of the crystal was an unusual process involving modeling with
      molecular graphics programs. The solution shows a structure which formally
      belongs to the space group P2(1), with four dipeptide molecules and four solvent
      molecules in the asymmetric unit (Z = 8). Additional non-crystallographic
      symmetry in three dimensions fixes all cell angles, including beta, to 90
      degrees. L-Leucyl-L-valine-2-propanol (1/1) is structurally closely related to
      the ethanol solvate, but owing to a rare type of packing disorder the length of
      the a axis is halved (Z = 4, P2(1)2(1)2(1)). The hydrogen-bonding pattern is
      still the same as in the ethanol solvate, which means that the hydrogen-bond
      periodicity along the a axis in the 2-propanol solvate is two unit-cell lengths.

PMID- 10927345
TI  - Structure of mono-acid even-numbered beta-triacylglycerols.
AB  - The crystal structure of the beta polymorph of tripalmitin (1,2,3
      trihexadecanoylglycerol, beta-PPP) has been determined by single-crystal X-ray
      diffraction. The molecules crystallize in space group P1; in an asymmetric tuning
      fork conformation. This structure and the already-known crystal structures of
      beta-tricaprin (beta-CCC) and beta-trilaurin (beta-LLL) could be matched in an
      overlap model. Apart from a difference in chain length, the three structures are
      almost identical. The overlap model can be used to predict the crystal structure
      of the other members of the C(n)C(n)C(n)-type (n = even) TAG series reasonably
      accurately. This is demonstrated by predicting the crystal structure for beta
      trimyristin (beta-MMM) and successively comparing the experimental and calculated
      X-ray powder diagrams.

PMID- 10927346
TI  - 3,4:9,10-Perylenetetracarboxylic dianhydride (PTCDA) by electron crystallography.
AB  - The crystal structures of the alpha and beta modifications of PTCDA were analyzed
      as projected structures along the a axes by electron crystallography using an
      imaging plate. The results for the alpha modification agree well with the sheet
      and-stack structure obtained by X-ray diffraction by M. L. Kaplan et al. (private
      communication, full set of crystal structure data). Projected onto the (102)
      plane, which is parallel to the molecular sheets, the long molecular axis makes
      an angle of 42 degrees with the b axis and the hexagonal benzene rings appear
      slightly elongated, indicating a slight inclination of the molecular plane from
      the (102) lattice plane. For the beta modification, it was concluded that the
      molecules are aligned in a herringbone packing scheme on the (102) plane similar
      to that of the alpha modification, but with a slightly different angle of the
      long molecular axis with the b axis (38 degrees ).

PMID- 10927347
TI  - Theoretical prediction of bond-valence networks. II. Comparison of the graph
      matrix and resonance-bond approaches. Erratum.
AB  - The correct version of Fig. 2 in the paper by Rutherford [Acta Cryst. (1998),
      B54, 204-210] is given. It shows that, assuming graph-equivalent bonds are equal,
      there are 57 possible bond-length sequences for beta-Ga(2)O(3) within the
      constraints of the Valence-Sum Rule.

PMID- 10927348
TI  - International Union of Crystallography Acta Crystallographica Section B Notes for
      Authors.

PMID- 10927349
TI  - Analysis of the environment of beryllium, magnesium and alkaline earth atoms in
      oxygen-containing compounds.
AB  - About 2100 inorganic and organometallic compounds containing beryllium, magnesium
      and alkaline earth atoms (M) were investigated with Voronoi-Dirichlet polyhedra
      (VDPs). It is shown that the coordination numbers (CNs) of the M atoms in MO(n)
      coordination polyhedra can be determined by means of VDPs without crystal
      chemical radii. The distributions of the M-O distances in the coordination
      spheres of the M atoms are bimodal for M = Be or Mg and monomodal for the other
      alkaline earth metals. Beryllium and magnesium coordination polyhedra containing
      weak M-O contacts were classified by variants of their distortions. It is found
      that the volume of the domains of the Mg, Ca, Sr and Ba atoms is independent of
      their CNs at CN >/= 6 (up to 16 for barium). The possibility of using the model
      of deformable spheres to describe the crystal structure of the compounds
      investigated is suggested.

PMID- 10927350
TI  - Concerning inorganic crystal structure types.
AB  - All representatives of an inorganic crystal structure type can be found
      systematically in the new database SICS (Standardized Inorganic Crystal
      Structures). It is derived from the Inorganic Crystal Structure Database (ICSD)
      by selecting the best determination of each phase. In addition, each entry is
      given in a standardized description and complemented by searchable descriptors
      Delta, which give the difference between all structures of an isopointal set.
      Because of the large number of structures the full information on relationships
      present can only be found by means of the new database itself. Some examples are
      given here in printed form. The limitations and the possibilities of expansion of
      SICS in terms of the concept of 'structure types' are demonstrated.

PMID- 10927351
TI  - Solution and refinement of the crystal structure of Bi7Ta3O18.
AB  - The structure of heptabismuth tritantalum octadecaoxide, Bi(7)Ta(3)O(18), has
      been solved and refined using single-crystal X-ray diffraction data collected at
      a synchrotron source in conjunction with unit-cell and symmetry information
      derived from electron diffraction. The space-group symmetry is triclinic C1 but
      is very close to monoclinic C2/m. A twin component observed during data
      collection was successfully modelled in the refinement. The C2/m prototype fitted
      all the Rietveld-refinable features of a medium-resolution neutron powder
      diffraction pattern. The metal-atom array is approximately face-centred cubic
      (fluorite type), punctuated by regularly spaced displacement faults perpendicular
      to the [111](fluorite) direction every 2.5 fluorite unit cells. The metal-atom
      populations and O-atom positions are fully ordered. The Ta(5+) cations are
      octahedrally coordinated, with TaO(6) octahedra forming columns. The remaining O
      atoms occupy distorted fluorite positions. The Bi(3+) cations occupy octahedral,
      square pyramidal or trigonal prismatic sites within the O-atom array; strain in
      the latter coordination environment appears to be responsible for the lowering of
      symmetry from monoclinic to triclinic.

PMID- 10927352
TI  - Iodo-oxyapatite, the first example from a new class of modulated apatites.
AB  - Iodo-oxyapatite [pentadecacalcium iodide oxide nonaphosphate, Ca(15)(PO(4))(9)IO]
      was synthesized by a flux method and the structure was solved from single-crystal
      X-ray data. The crystal structure was refined in the space group P6(3)/m [a =
      9.567 (1), c = 20.754 (2) A and Z = 2] to wR on F of 0.0459. Iodo-oxyapatite has
      a typical hexagonal apatite structure but the unit cell is tripled along the
      hexad owing to ordering of the iodide and oxide ions along this direction.

PMID- 10927353
TI  - Elucidation of the crystal structure of oxyapatite by high-resolution electron
      microscopy.
AB  - High-resolution electron-microscopy (HREM) images from different hydroxyapatite
      (OHAp) samples showed p3 projection symmetry along [001] instead of the p6
      projection symmetry compatible with the space group P6_3/m of OHAp. Image
      processing was used to establish without ambiguity that threefold symmetry
      dominates the images along [001]. OHAp crystals decompose in the transmission
      electron microscope and it is concluded that the threefold symmetry observed
      corresponds to an early step in the decomposition process, the dehydration of
      OHAp to oxyapatite (OAp). A structural model for OAp where every second O atom
      along the 6(3) axis in OHAp is removed has the maximal space-group symmetry
      P{?bar 6}. This is compatible with the p3 projection symmetry observed. Atomic
      shifts in this OAp model compared to the OHAp structure were estimated using the
      HREM images and geometric optimizations of the atomic structure. No refinements
      of the atomic coordinates against diffraction data were possible but the
      simulated HREM images of this crude model fit well with the experimental images.

PMID- 10927354
TI  - Search for Pnma materials with high-temperature structural phase transitions.
AB  - A systematic search for structures having a high-temperature structural phase
      transition can be carried out through the identification in the structural
      databases of those structures that can be considered pseudosymmetric.
      Pseudosymmetry in a crystal structure indicates the possibility of a similar
      configuration of higher symmetry. If the distortion relating both structures is
      small enough, it can be expected that the crystal acquires the more symmetric
      configuration through a Landau-type phase transition at a higher temperature.
      Here, we present the results of such a search among inorganic structures with
      space group Pnma retrieved from the Inorganic Crystal Structure Database.
      Pseudosymmetry has indeed been detected in those compounds with a known
      (displacive) Landau-type phase transition at higher temperatures. This is
      measured by a parameter Delta, which measures the maximal atomic displacement
      relating the pseudosymmetry-transformed structure and the original one. In most
      of these compounds with a known phase transition, this parameter was smaller than
      1.0 A for at least one minimal supergroup of Pnma. The database contains 144
      additional structures with pseudosymmetry features under the same quantitative
      limit. A comparison of the Delta distributions in both sets of compounds suggests
      a smaller Delta window (with 0.7 A as maximal value) for selecting the materials
      having maximal probability of exhibiting a phase transition at higher
      temperatures. A set of 58 compounds fulfils this criterion.

PMID- 10927355
TI  - Crystallographic disorder in mixed-valent dioxo-bridged MnIII,IV complexes.
AB  - The structure of tetrakis(2,2'-bipyridine)di-u-oxo-dimanganese(3+)
      hexanitratocerate(3-) pentahydrate, [Mn(2)O(2)(bpy)(4)][Ce(NO(3))(6)].5H(2)O, is
      described; M(r) = 1368.88, monoclinic, C2/c, a = 12.940 (3), b = 18.060 (2), c =
      22.54 (1) A, beta = 96.29 (2) degrees, V = 5237 (3) A(3), T = 132 K, Z = 4,
      F(000) = 2752, D(x) = 1.736 Mg m(-3), lambda(Mo Kalpha) = 0.71073 A, u = 1.429
      mm(-1), R(F(2)) = 0.0358, wR(F(2)) = 0.0783 for 4877 reflections with I >
      2sigma(I). The cation does not have crystallographically distinguishable Mn
      atoms. An analysis of the atomic displacement ellipsoids and Mn-N bond
      distortions has been used to develop a model for the disorder in this type of
      mixed-valent complex. The anion, Ce(NO(3))(6)(3-), has a distorted icosahedral
      geometry.

PMID- 10927356
TI  - Charge and momentum densities of cubic tetracyanoethylene and its insertion
      compounds.
AB  - Charge and momentum electron densities provide complementary views of cohesive
      forces in solids. This is particularly true for molecular crystals. The examples
      of cubic tetracyanoethylene (1,1,2,2-ethenetetracarbonitrile) and its alkali
      metal insertion compounds are analyzed from a theoretical point of view. Besides
      the usual deformation density maps and anisotropy of Compton profiles, it is
      shown that interaction charge density and interaction Compton profiles can be
      defined and reveal the subtleties of the intermolecular interactions. It is shown
      that owing to the large cavities in the crystal, alkali-metal atoms can be
      inserted, leading to a strong charge transfer to the molecules and to a metallic
      character; the mechanism of insertion is revealed well by the combination of
      charge and momentum density studies. The combination of the two techniques of X
      ray diffraction and Compton scattering should be of great help in the study of
      rather weak interactions present in molecular solids.

PMID- 10927357
TI  - Conformational behaviour of bridging diphenylphosphido ligands.
AB  - Data retrieved from the Cambridge Structural Database for crystal structures
      containing (u-diphenylphosphido) metal complexes, [M(2){u-PPh(2)}] (where M is a
      d-block element), have been analysed to evaluate the conformational behaviour of
      these species. The observed distribution of torsion angles about the P-C bonds
      has been compared with the potential energy surface (PES) for phenyl rotations in
      a representative species [(AuBr)(2){u-PPh(2)}](-) computed using the universal
      force field. Good agreement was obtained between the low-energy (<8 kJ mol(-1)
      above the global minimum) regions of the PES and the occupied regions of the two
      dimensional P-Ph rotor conformation space. Phenyl ring rotations occur by
      coupled, geared disrotatory and uncoupled conrotatory motions of the phenyl
      groups in this and other classes of PPh(2) rotors.

PMID- 10927358
TI  - Experimental evidence for the amino-group non-planarity in nitroanilines: neutron
      diffraction study of 2-methyl-5-nitroaniline at 100 K.
AB  - An appreciable degree of pyramidalization of the amine N atom is observed in the
      title compound. The existence of polar chains, induced by N-H.O synthons, is
      confirmed. C-H.O interactions, not noted in a previous X-ray study, were found to
      stabilize further the known head-to-tail assembling of the chains. The structure
      can be described as non-polar (101) layers, embodying chains interlinked by
      centrosymmetric dimers, connected by C(aryl)-H.pi interactions. The latter are
      not present in m-nitroaniline, 2-methyl-4-nitroaniline and other related
      compounds with chains built from similar N-H.O synthons and assembled head-to
      head. This finding implies that an obvious relationship between molecular
      recognition patterns and crystal structures should not be assumed.

PMID- 10927359
TI  - Hydrogen-bonding interactions in the crystalline-phase structures of cinnamic
      acid derivatives.
AB  - Secondary interactions responsible for the crystalline-phase structures of
      various cinnamic acids and cinnamic acid esters drawn from the Cambridge
      Structural Database were studied with the help of the Cerius package implemented
      on an SGI workstation. Primarily hydrogen-bonding interactions were sought, but
      deviation from planarity was also measured. For the acids, the main structural
      feature is the strong hydrogen bonding between the carboxyl groups. The dimers
      are interconnected by C-H.O intermolecular hydrogen bonds. In most cases the C
      atom of the C-H unit was a member of the aromatic ring. Intramolecular (olefinic)
      C-H.O bonds were found to be frequent, fixing synperiplanar and antiperiplanar
      C=C-C=O conformations with about the same abundance in the acids and exclusively
      synperiplanar conformations in the esters. The carbonyl group of the ester is
      always involved in C-H.O hydrogen bonding. Here, the C atom of the C-H unit was
      either a member of the aromatic ring or the olefinic group, or was attached to
      the alcoholic O atom of the ester group. The beta-phenyl and the carboxyl or the
      ester groups are almost coplanar. The crystals have a layered structure and in
      the most frequent parallel arrangement the phenyl groups are offset by varing
      amounts (but always to a small extent) in neighbouring layers. The common
      hydrogen bonds are mostly within a layer.

PMID- 10927360
TI  - Interaction of lysine with iodic acid.
AB  - A new compound in the Lys-HIO(3)-H(2)O system (where Lys = lysine), lysine-iodic
      acid (1/3), C(6)H(14)N(2)O(2).3HIO(3), has been discovered. Its crystals display
      nonlinear optical properties. They were investigated by X-ray analysis, IR
      spectroscopy and NQR methods. The parameters of the unit cell are a = 8.360 (2),
      b = 6.330 (1), c = 14.750 (3) A, beta = 92.86 (3) degrees, D(x) = 2.87 Mg m(-3),
      space group P2(1), Z = 2. The three iodate groups in the structure have different
      roles. Interaction of lysine and iodic acid results in a compound containing a
      doubly protonated lysine cation and two counterions, IO(3)(-) and I(2)O(5)OH(-).

PMID- 10927361
TI  - Charge density study of N-acetyl-L-tyrosine ethyl ester monohydrate derived from
      CCD area detector data.
AB  - The crystal structure, thermal vibrations and electron density of the peptide N
      acetyl-L-tyrosine ethyl ester monohydrate, C(13)H(17)NO(4).H(2)O, have been
      analysed using single-crystal X-ray diffraction data collected at 110 K with Mo
      Kalpha radiation to a resolution of (sinstraight theta/lambda)(max) = 1.1 A(-1).
      A CCD area detector was used to collect 98 393 data during one week. A multipolar
      atom density model was fitted against the 10 189 unique data with I > 2sigma(I)
      [R(F) = 0.027, wR(F) = 0.020, g.o.f. = 0.65] in order to map the valence electron
      distribution. These deformation densities compare very well with those obtained
      from conventional diffractometers equipped with scintillation detectors. This
      work shows that area detectors permit charge density studies in a more routine
      way than is possible with conventional diffractometers.

PMID- 10927362
TI  - TEMPO radicals showing magnetic interactions. I. 4-(4-Halobenzylideneamino)TEMPO
      and related compounds.
AB  - X-ray crystal structure analyses of the 4-(4-halobenzylideneamino)TEMPO (TEMPO =
      2,2,6,6-tetramethylpiperidyl-1-oxyl) radicals 4-(4-fluorobenzylideneamino)
      2,2,6,6-tetramethylpiperidyl-1-oxyl, 4-(4-chlorobenzylideneamino)-2,2,6,6
      tetramethylpiperidyl-1-oxyl, 4-(4-bromobenzylideneamino)-2,2,6,6
      tetramethylpiperidyl-1-oxyl and 4-(4-iodobenzylideneamino)-2,2,6,6
      tetramethylpiperidyl-1-oxyl, and other 4-Ar-CH=N-TEMPO [Ar = 4-Ph-Ph, 2,2,6,6
      tetramethyl-4-(4-phenylbenzylideneamino)piperidyl-1-oxyl, 4-Py, 2,2,6,6
      tetramethyl-4-(4-pyridylmethylideneamino)piperidyl-1-oxyl, and 3,5-diCl-Ph, 4
      (3,5-dichlorobenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl] radicals have
      been performed at room temperature. Some of these radicals show intermolecular
      ferromagnetic interactions at extremely low temperatures. X-ray analysis revealed
      that crystals of the 4-I-Ph derivative showed two modifications [(a) and (b)];
      measurements of the magnetic properties of these crystals showed a ferromagnetic
      transition at an extremely low temperature for modification (a) and an
      antiferromagnetic interaction for modification (b). The structural features of
      these TEMPO radical crystals can be classified into three groups: (i) the crystal
      structures of the 4-Cl-Ph, 4-I-Ph(a) and 4-Ph-Ph derivatives, which show a
      ferromagnetic transition; (ii) the structures of the 4-Br-Ph and 4-Py
      derivatives, which show a ferromagnetic interaction (straight theta > 0); (iii)
      miscellaneous: the antiferromagnetic 4-F-Ph and 4-I-Ph(b) derivatives (straight
      theta < 0) and the ferromagnetic 3,5-diCl-Ph (straight theta > 0) derivative.
      Sheet-like arrangements of O atoms and intra-sheet interactions through the CH(2)
      or CH(3) groups of the TEMPO rings are related to the mechanisms of the
      ferromagnetic interactions.

PMID- 10927363
TI  - Identification of a new trace 114R SiC by HREM.
AB  - Using electron diffraction patterns and high-resolution electron microscopy
      (HREM), a trace 114R SiC in commercial alpha-SiC powder (mainly 6H SiC according
      to X-ray diffraction) has been discovered. In a hexagonal unit cell its stacking
      sequence is [(33)(4)(34)(2)](3), the periodicity along the c axis is 286.14 A and
      a = b = 3.073 A. 114R belongs to the structure series of (33)()n34(33)()m34
      predicted theoretically by Pandey & Krishna [Mater. Sci. Eng. (1975), 20, 243
      249] on the basis of the faulted matrix model.

PMID- 10927364
TI  - Energetic study of the disordered solvent in the crystal structure of an
      isoxazole derivative. Erratum.
AB  - An error in printing is reported. In the paper by Pani et al. [Acta Cryst.
      (1998), B54, 872-876] the value of Deltarho(max) is given incorrectly in the last
      sentence on page 874. The sentence should read 'In the last difference Fourier
      map, the highest Deltarho values were found near the Cl atoms (Deltarho(max)
      +0.32 e A(-3)); the final reliability indexes were R(1) = 0.072 over 1762 F(o) >
      4sigma(F(o)) and wR(2) = 0.228 on 4029 F(o)(2) for 245 refined parameters, with a
      goodness-of-fit of 0.96.'

PMID- 10927366
TI  - Crystal lattice and phase transitions in Na4TiP2O9 (NTP) and Na4.5FeP2O8(O,F)
      (NFP) superionic conductors as a function of high pressures and temperatures.
AB  - The lattice dynamics of Na(4)TiP(2)O(9) (tetrasodium titanium diphosphorus
      nonaoxide, NTP) and Na(4.5)FeP(2)O(8)(O,F) (nonasodium diiron tetraphosphorus
      difluoride octadecaoxide, NFP) crystals, which are superionic conductors with
      Na(+)-ion conductivity, were studied under high pressures. Lattice constants as a
      function of hydrostatic pressure were measured on a four-circle diffractometer
      using a high-pressure cell with diamond anvils. At 1.78 +/- 0.15 GPa NTP
      undergoes a reversible phase transition from the modulated monoclinic (pseudo
      orthorhombic) modification which is stable under atmospheric conditions. A
      similar phase transition in NTP is observed at 523 K. For NFP, it may be assumed
      that at least three phase transitions occur when the pressure increases from
      atmospheric to 12 GPa, at 1.39 +/- 0.08, 4.52 +/- 0.32, and 6.02 +/- 0.02 GPa, as
      concluded from the change in the unit-cell parameters and in the color of the
      crystals: the color changes from ginger (dark orange) to pink at ~1.5-2.0 GPa
      pressure and to violet at ~6.0 GPa.

PMID- 10927367
TI  - Cation distribution and crystal chemistry of Y3Al5-xGaxO12 (0 </= x </= 5) garnet
      solid solutions.
AB  - Five single crystals of Y(3)Al(5-x)Ga(x)O(12) (0 </= x </= 5) garnet solid
      solutions with the compositions x = 0.0, 1.0, 2.0, 3.0 and 4.0 were synthesized
      using a flux method. The compositional dependence of the lattice constants of the
      garnet solid solutions shows a large deviation from Vegard's law. Investigation
      of the cation distributions of these garnets using single-crystal X-ray
      diffraction shows that Ga(3+), which is larger than Al(3+), preferentially
      occupies the tetrahedral (four-coordinate) site rather than the octahedral (six
      coordinate) site. On the basis of the results obtained from structure
      refinements, geometric analyses of the polyhedral distortions were carried out.
      The results imply that the cation-cation repulsive force across the polyhedral
      shared edges decreases with increasing substitution of Ga(3+). Moreover, the
      proportion of covalent bonding in the cation-oxygen bonds was estimated from the
      bond strength; the results indicate that the covalency of the Ga-O bond is
      greater than that of the Al-O bond. The peculiar cation distributions observed in
      the Y(3)Al(5-x)Ga(x)O(12) garnet solid solutions are most probably caused by the
      strong covalency of the Ga-O bond and also simultaneously induced by the need to
      decrease the cation-cation repulsive force. Crystal data: cubic, Ia3;d, Z = 8, Mo
      Kalpha, lambda = 0.71069 A; at x = 0.0 (triyttrium pentaaluminium dodecaoxide):
      a(0) = 12.0062 (5) A, V = 1730.7 (2) A(3), D(x) = 4.56 Mg m(-3), M(r) = 593.613,
      u = 21.21 mm(-1), F(000) = 2224, R = 0.029 for 294 reflections; at x = 1.0
      (triyttrium tetraaluminium gallium dodecaoxide): a(0) = 12.0432 (7) A, V = 1746.7
      (3) A(3), D(x) = 4.84 Mg m(-3), M(r) = 636.351, u = 24.09 mm(-1), F(000) = 2368,
      R = 0.022 for 124 reflections; at x = 2.0 (triyttrium trialuminium digallium
      dodecaoxide): a(0) = 12.0926 (9) A, V = 1768.3 (4) A(3), D(x) = 5.10 Mg m(-3),
      M(r) = 679.089, u = 26.85 mm(-1), F(000) = 2512, R = 0.018 for 144 reflections;
      at x = 3.0 (triyttrium dialuminium trigallium dodecaoxide): a(0) = 12.1552 (6) A,
      V = 1795.9 (3) A(3), D(x) = 5.34 Mg m(-3), M(r) = 721.827, u = 29.43 mm(-1),
      F(000) = 2656, R = 0.018 for 184 reflections; at x = 4.0 (triyttrium aluminium
      tetragallium dodecaoxide): a(0) = 12.2123 (8) A, V = 1821.3 (4) A(3), D(x) = 5.58
      Mg m(-3), M(r) = 764.565, u = 31.97 mm(-1), F(000) = 2800, R = 0.014 for 159
      reflections.

PMID- 10927368
TI  - Electron density distribution and Madelung potential in alpha-spodumene,
      LiAl(SiO3)2, from two-wavelength high-resolution X-ray diffraction data.
AB  - The electron density distribution in alpha-spodumene, LiAl(SiO(3))(2), was
      derived from high-resolution X-ray diffraction experiments. The results obtained
      from both Mo Kalpha- and Ag Kalpha-wavelength data sets are reported. The
      features of the Si-O and Al-O bonds are related to the geometrical parameters of
      the Si-O-Al and Si-O-Si bridges on the one hand and to the O.Li(+) interaction on
      the other. Kappa refinements against the two data sets yielded almost the same
      net charges for the Si (+1.8 e) and O (-1.0 e) atoms in spodumene. However, the
      Al net charge obtained from the Ag Kalpha data (+1.9 e) is larger than the net
      charge derived from the Mo Kalpha data (+1.5 e). This difference correlates with
      a more contracted Al valence shell revealed by the shorter X-ray wavelength
      (kappa = 1.4 for the Ag Kalpha data set). The derived net charges were used to
      calculate the Madelung potential at the spodumene atomic sites. The electrostatic
      energy for the chemical formula LiAl(SiO(3))(2) was -8.60 e(2) A(-1) (-123.84 eV)
      from the net charges derived from the Ag Kalpha data and -6.97 e(2) A(-1) (
      100.37 eV) from the net charges derived from the Mo Kalpha data.

PMID- 10927369
TI  - Single-crystal neutron diffraction study of beta-Cs3(HSO4)2
AB  - The structure of beta-Cs(3)(HSO(4))(2)[H(2-x)(S(x)P(1-x))O(4)] has been examined
      by single-crystal neutron diffraction at 15 K. The compound crystallizes in space
      group C2/c and contains four formula units in the unit cell, with lattice
      parameters a = 19.769 (9), b = 7.685 (2), c = 8.858 (3) A and beta = 100.60 (4)
      degrees. Refinement of P, S and H site occupancies indicated that the value of x
      (in the stoichiometry) is 0.500 (6). This, together with the unit-cell volume of
      1322.8 (14) A(3), implies a density of 3.463 Mg m(-3). The structure contains
      zigzag rows of XO(4) anions, where X = P or S, that alternate, in a checkerboard
      fashion, with zigzag rows of Cs cations. Moreover, there is one proton site,
      H(3), with an occupancy of 0.25 and one X-atom site, X(1), that is occupied by
      0.5 P and 0.5 S. These features are in general agreement with a previous X-ray
      structure determination carried out at 298 K. In contrast to the X-ray study,
      however, it was found that two different structural models adequately fit the
      diffraction data. In the first model, the proton vacancies and the P atoms were
      assumed to be randomly distributed over the H(3) and X(1) sites, respectively,
      and to have no impact on the local structure. In the second model, several atoms
      were assigned split occupancies over two neighboring sites, to reflect the
      presence or absence of a proton vacancy, and the presence of P or S on the X(1)
      site. Refinement assuming the first model, in which anisotropic displacement
      parameters for 12 of 14 atom sites in the asymmetric unit were employed, yielded
      residuals wR(F(2)) = 0.084 and wR(F) = 0.038. For the second model, in which
      anisotropic displacement parameters were utilized for only the five atoms that
      were not split relative to the first model, the residuals were wR(F(2)) = 0.081
      and wR(F) = 0.036.

PMID- 10927370
TI  - Arrangement of C atoms in the SiC-C solid solution.
AB  - The microstructure of a silicon carbide-carbon solid-solution powder (SiC-C),
      obtained from a fine powder of silicon and thermal expansive graphite, is
      investigated by X-ray powder diffraction methods. The microstructure is
      characterized by Williamson-Hall analysis and the strain-field model suggested by
      van Berkum et al. [Acta Cryst. (1996), A52, 730-747]. SiC-C adopts a layered
      structure like the solid solutions formed by compounds possessing a diamond-like
      structure, e.g. SiC-AlN. Superstoichiometric C atoms are located as planar
      defects. The SiC-C solid solution is destroyed on heating in a vacuum in the
      temperature range of graphitization of diamond but is maintained after sintering
      at high pressure (4-8 GPa) and high temperature (1673 and 2073 K). However, at
      the higher temperature (2073 K), it is observed that planar defects formed by C
      atoms decompose to non-correlated point defects accompanied simultaneously by a
      decrease in the lattice parameter from 4.3540 (2) to 4.35234 (5) A.

PMID- 10927371
TI  - Structures of Bi14WO24 and Bi14MoO24 from neutron powder diffraction data.
AB  - The (isomorphous) structures of Bi(14)WO(24), tetradecabismuth tungsten
      tetracosaoxide, and Bi(14)MoO(24), tetradecabismuth molybdenum tetracosaoxide,
      have been solved and refined using neutron powder diffraction data in the space
      group I4/m. The metal-atom array is fully ordered in terms of composition, and in
      terms of atomic positions deviates only slightly from a fluorite-type delta
      Bi(2)O(3)-related parent structure. Three independent O-atom sites (accounting
      for 70 out of 78 O atoms in the unit cell) are also very close to fluorite-type
      parent positions. The remaining two O-atom sites, which coordinate W, exhibit
      partial occupancies and displacive disorder, neither of which could be better
      modelled by lowering of symmetry. The W site is coordinated by four O atoms in
      highly distorted tetrahedral coordination, the tetrahedron necessarily being
      orientationally disordered on that site. Nonetheless, the structure appears to be
      chemically reasonable.

PMID- 10927372
TI  - The crystal structure of Ca7Zr7Ta6O36 refined using synchrotron-radiation data.
AB  - Single-crystal X-ray diffraction data [synchrotron radiation; lambda = 1.2682 (4)
      A] are used to solve and refine the crystal structure of heptacalcium
      hexatantalum heptazirconium hexatriacontaoxide, Ca(7)Zr(7)Ta(6)O(36). The
      structure adopts space group Fddd with cell dimensions a = 36.394 (1), b = 7.3674
      (5), c = 31.006 (2) A. The structure was solved by direct methods. Refinement
      using 1299 unique reflections leads to final values of R = 0.031 and wR = 0.034.
      The refined metal-atom ordering scheme is far from fully ordered and reminiscent
      of the A/B metal-atom ordering characteristic of the pyrochlore structure type.
      Bond-valence sums are calculated to confirm the plausibility of the crystal
      chemistry of Ca(7)Zr(7)Ta(6)O(36).

PMID- 10927373
TI  - Synchrotron X-ray analysis of the electron density in HoFe2.
AB  - Structure factors for a small holmium diiron HoFe(2) Laves crystal were measured
      with focused lambda = 0.75 A synchrotron X-radiation using a fast avalanche
      photodiode (APD) counter. The deformation electron density (Deltarho) maps are
      remarkable for significant excess electron density midway between the Ho atoms,
      which is not dissimilar to the peaks attributed to classic 'covalent bonding' in
      C and Si crystals. These residual electrons accumulate at the centres of the
      kagome net hexagons and form, with the Fe atoms, a triangular lattice which is
      characterized by more stable magnetic order than the kagome net. Similar peaks
      occur along the Ho-Fe and Fe-Fe contacts. These results confirm the hypothesis
      that 5d electrons of the rare-earth atoms are important in the spin-coupling
      mechanism for HoFe(2)-type compounds. The 5d electrons are far less localized
      than the 4f electrons, and considerable 5d-5d and 5d-3d orbital overlap occurs
      between neighbouring atoms. Aspherical electron density near the Ho nuclei can be
      associated with the Ho 4f subshell electrons. Strong depletions of the Deltarho
      near the atoms along the Ho-Ho, Ho-Fe and Fe-Fe vectors are indications of
      exchange repulsion. The effect of anharmonicity on the Deltarho is insignificant.

PMID- 10927374
TI  - Determination of the site of incorporation of cobalt in CoZnPO-CZP by multiple
      wavelength anomalous-dispersion crystallography.
AB  - Data were collected from a crystal of CoZnPO-CZP {sodium cobalt-zinc phosphate
      hydrate, Na(6)[Co(0.2)Zn(0.8)PO(4)](6).6H(2)O} using synchrotron radiation at
      ELETTRA at the inflection point and 'white line' for both the cobalt and zinc K
      edges, and at 1.45 A, a wavelength remote from the K edges of both metals. The
      data were processed using the programs DENZO and SCALEPACK. The CCP4 program
      suite was used for the scaling of data sets and the subsequent calculation of
      dispersive difference Fourier maps. Optimal scaling was achieved by using a
      subset of reflections with little or no contribution from the metal atoms (i.e.
      which were essentially wavelength independent in their intensities) and using
      weights based on the sigma's to obtain an overall scale factor in each case.
      Phases were calculated with SHELXL97 based on the refined structure using a much
      higher resolution and complete Cu Kalpha data set. An occupancy of 100% by zinc
      at the two metal-atom sites was assumed. The dispersive difference Fourier map
      calculated for zinc gave two peaks above the background of similar heights at the
      expected metal-atom sites. The peak height at the Zn1 site was a little higher
      than at the Zn2 site. The dispersive difference Fourier map calculated for cobalt
      gave just one peak above the background, at the Zn1 site, and only a small peak
      at the Zn2 site, thus indicating that incorporation of cobalt takes place mainly
      at one site. Refinement of the zinc occupancies using MLPHARE reinforces this
      conclusion. The chemical environment of each site is discussed.

PMID- 10927375
TI  - Structural investigation of the negative-thermal-expansion material ZrW2O8.
AB  - High-resolution powder diffraction data have been recorded on cubic ZrW(2)O(8) [a
      = 9.18000 (3) A at 2 K] at 260 temperatures from 2 to 520 K in 2 K steps. These
      data have confirmed that alpha-ZrW(2)O(8) has a negative coefficient of thermal
      expansion, alpha = -9.07 x 10(-6) K(-1) (2-350 K). A 'parametric' approach to
      Rietveld refinement is adopted and it is demonstrated that a full anisotropic
      refinement can be performed at each temperature, despite using a data collection
      time of only 5 min. Examination of the resulting structural parameters suggests
      that the origin of the contraction with increasing temperature can be traced
      straightforwardly to the rigid-body transverse librations of bridging O atoms.
      alpha-ZrW(2)O(8) undergoes a phase transition from P2(1)3 to Pa3; at 448 K that
      is associated with the onset of considerable oxygen mobility. The phase
      transition can be described in terms of a simple cubic three-dimensional Ising
      model. Unusual kinetics are associated with this phase transition. Hysteresis in
      the cell parameter through the phase transition is the opposite of that normally
      observed.

PMID- 10927376
TI  - Disparate atomic displacements in skutterudite-type LaFe3CoSb12, a model for
      thermoelectric behavior.
AB  - Mean-square atomic displacements in lanthanum triiron cobalt dodecaantimonide,
      determined as a function of temperature using single-crystal neutron diffraction,
      show that the La atom exhibits an anomalously large displacement at room
      temperature, U(eq) = 0.0196 (9) A(2), because it is too small to fill the atomic
      cage formed by the corner-linked octahedral framework of M(4)Sb(12), M = Fe, Co.
      Site-occupancy refinements show 25% vacancies on the La site and an actual Fe:Co
      ratio of 2.17:1. Analysis of the temperature dependence of the atomic
      displacements identifies a significant temperature-independent component for the
      La atom ascribed to static disorder, which amounts to 19% of the room-temperature
      value. The large-amplitude rattling of the La atom can be effectively linked to
      the dramatic decrease of the lattice contribution to the thermal conductivity,
      which is a key factor for improving the thermoelectric behavior of these
      materials. This structure-property relationship offers a new paradigm for the
      exploration of thermoelectric materials.

PMID- 10927377
TI  - The crystal structure of the B-site ordered complex perovskite Sr(Yb0.5Nb0.5)O3.
AB  - The room-temperature crystal structure of the B-site ordered complex perovskite
      strontium ytterbium niobate, Sr(Yb(0.5)Nb(0.5))O(3) [monoclinic, Z = 2, P2(1)/n
      (set 2), a = 5.79095 (8), b = 5.82210 (7), c = 8.20358 (12) A, beta = 90.126 (1)
      degrees, with final R(wp) = 0.0595, R(Bragg) = 0.0203 for the neutron profile and
      R(wp) = 0.0832, R(Bragg) = 0.0193 for the X-ray profile, respectively], was
      determined by X-ray powder diffraction, high-resolution neutron powder
      diffraction and transmission electron microscopy. This compound shows a slight
      triclinic distortion from the prototype doubled cubic perovskite cell as a result
      of an a(-)a(-)c(+)-type oxygen octahedral tilting distortion. It is also shown
      that the site ordering of the different species of B-site cations, Yb(3+) and
      Nb(5+), inherently leads to a difference between the volumes of the YbO(6) and
      NbO(6) octahedra. This volume difference is shown to inevitably inhibit the rigid
      rotation of octahedra.

PMID- 10927378
TI  - Structure analysis of new homologous compounds Ga2O3(ZnO)m (m = integer) by high
      resolution analytical transmission electron microscopy.
AB  - The crystal structure of a new homologous compound series, Ga(2)O(3)(ZnO)(m) (m =
      integer), is determined by high-resolution lattice imaging and high spatial
      resolution energy-dispersive X-ray spectroscopy (EDS) analysis in a field
      emission analytical transmission electron microscope. This work was carried out
      mainly on the compound with m = 9 (digallium nonazinc dodecaoxide), which belongs
      to the orthorhombic system and has lattice constants a(o) = 0.33, b(o) = 2.0 and
      c(o) = 3.4 nm. From the extinction rules three possible space groups are selected
      and from them a unique space group is assigned as noncentrosymmetric Cmc2(1) (No.
      36) on the basis of structural requirements. Ga(2)O(3)(ZnO)(m) is a layered
      structure consisting of Ga-O and m + 1 Ga/Zn-O layers stacked alternately along
      the c axis. It is shown that the structure of Ga(2)O(3)(ZnO)(m) differs from that
      of M(2)O(3)(ZnO)(m) (M = In, Fe; m = integer) reported previously. In
      Ga(2)O(3)(ZnO)(m) the Ga atoms occupy the tetrahedral sites in the Ga-O layers,
      whereas the M atoms in the M-O layers occupy the octahedral sites in
      M(2)O(3)(ZnO)(m) (M = In, Fe).

PMID- 10927379
TI  - Accurate charge densities in days - use of synchrotrons, image plates and very
      low temperatures.
AB  - Extensive synchrotron (28 K) and conventional sealed-tube (9 K) X-ray diffraction
      data have been collected on tetrakis(dimethylphosphinodithioato-S,S')thorium(IV),
      [Th(S(2)PMe(2))(4)]. The use of very low temperatures, well below those obtained
      with liquid-nitrogen cooling, is crucial for the accuracy of the data. This is
      due to minimization of temperature-dependent systematic errors such as TDS and
      anharmonicity, and extension and intensification of the data in reciprocal space.
      Comparison of structural parameters derived separately from the sealed-tube data
      and the synchrotron data shows good agreement. The synchrotron data are markedly
      superior when comparing refinement residuals, standard uncertainties (s.u.'s) of
      the data and s.u.'s of the derived parameters. However, the study suggests that
      there are still small uncorrected systematic errors in the data. The very large
      extent [(sinstraight theta/lambda)(max) = 1.77 A(-1)] of the synchrotron data and
      the very low temperature at which they were collected makes it possible to
      separate anharmonic effects from electron-deformation effects even with only an X
      ray data set at a single temperature. The electron density shows a large
      polarization of the outer Th core of d-type symmetry. This deformation is
      successfully modelled with contracted multipolar functions, which are only
      slightly correlated with anharmonic expansions in reciprocal space when using the
      full extent of the data. In the data collection more than a factor of 100 in
      speed is gained by use of image-plate area detectors at the synchrotron source
      compared with conventional sequential measurements. Thus accurate, very low
      temperature synchrotron-radiation diffraction data can now be measured within
      days, which makes electron-density studies of compounds beyond the first
      transition series more frequently within reach.

PMID- 10927380
TI  - Thermal vibrations in potassium 3-benzoyl-2-thiophenecarboxylate.
AB  - The atomic thermal displacement parameters at 293 K for the anion in the title
      salt have been analyzed in terms of a body having two rigid segments, namely the
      benzoyl and the 2-thiophenecarboxylate groups. These segments are each nearly
      planar and have a dihedral angle of 80.1 degrees between them. The internal
      torsional libration of the anion is physically correlated with its overall
      external translational and librational motion. Bond distances involving the
      heavier atoms have an s.u. sigma from 0.002 to 0.003 A while librational
      corrections in these distances range up to 4sigma. A short nonbonded intersegment
      C.O distance of 2.817 (2) A becomes 2.831 A after correction, the correction
      being 7sigma. An intermolecular S.O distance of 3.1891 (14) A becomes 3.215 A
      after correction for independent vibration of the two molecules, the correction
      being 18sigma.

PMID- 10927381
TI  - Four-component intergrowth structures of the metal-ion cage complexes fac
      (1,5,9,13,20-pentamethyl-3,7,11,15,18,22-hexaazabicyclo
AB  - The crystal structures of (1,5,9,13,20-pentamethyl-3,7,11,15,18,22
      hexaazabicyclo[7.7.7]tricosane-kappa(6)N,N',N",N"',N"",N""')nickel(II)
      diperchlorate-x(water) (x = 0.530), [Ni(C(22)H(48)N(6))](ClO(4))(2).0.530H(2)O,
      and (1,5,9,13,20-pentamethyl-3,7,11,15,18,22-hexaazabicyclo[7.7.7]tricosane
      kappa(6)N,N',N",N"',N"",N""')zinc(II) diperchlorate-x(water) (x = 0.608),
      [Zn(C(22)H(48)N(6))](ClO(4))(2).0.608H(2)O, are isomorphic and each is described
      as an intergrowth of four substructures, consistent with different modulations of
      an idealized parent structure of space group C2/c. Two substructures correspond
      to alternative orientations of a C1; structure for which x = 0 in the general
      formula [M(C(22)H(48)N(6))](ClO(4))(2).xH(2)O, and two substructures correspond
      to alternative origins of a P2(1)/n structure for which x = 1. Twinning also
      occurs. An analysis of the pseudosymmetry, a description of the refinement and a
      description of the refined structures are presented. The MN(6) coordination
      geometry is essentially octahedral, in contrast to the trigonal-prismatic
      geometry observed for the Cd(II) and Hg(II) complexes of the same ligand.

PMID- 10927382
TI  - Crystal structures of
AB  - The crystal structures of [18]aneN(6)H(2)K[Co(CN)(6)].4H(2)O [potassium
      dihydrogen hexacyanocobaltate-1,4,7,10,13,16-hexaazacyclooctadecane-water
      (1/1/4)], [16]aneN(4)H(2)K[Co(CN)(6)] [potassium dihydrogen hexacyanocobaltate
      1,5,9,13-tetraazacyclohexadecane (1/1)] and [12]aneN(4)H(3)[Co(CN)(6)].2H(2)O
      [trihydrogen hexacyanocobaltate-1,4,7,10-tetraazacyclododecane-water (1/1/2)]
      have been determined. For these supercomplexes, the [Co(CN)(6)](3-) binding with
      protonated polyammonium macrocycles is dominant in the binding competition
      between K(+) and [Co(CN)(6)](3-). It is suggested that the binding of
      [Co(CN)(6)](3-) with protonated polyammonium macrocycles is independent of the
      cavity size of the macrocycle, whereas that of K(+) is size-match selective. For
      [18]aneN(6)H(2)K[Co(CN)(6)].4H(2)O, the formation of a two-dimensional lamella
      may be derived from a chain-like arrangement of four-, five- and eight-membered
      rings in the network through the mutual balance between electrostatic and
      hydrogen-bonding interactions. [16]aneN(4)H(2)K[Co(CN)(6)] is a novel example
      demonstrating the anchoring of cobalticyanide through hydrogen-bonding
      interactions inside a zeolite-type cavity in the three-dimensional network formed
      by K(+) and the macrocycles through Coulombic interactions. Also, a three
      dimensional network was formed mainly through hydrogen-bonding interactions
      between [Co(CN)(6)](3-), protonated macrocycles and water molecules in
      [12]aneN(4)H(3)[Co(CN)(6)].2H(2)O.

PMID- 10927383
TI  - Polynuclear chloromercurate(II) systems in their chloropyridinium salts.
AB  - The chloromercurate(II) salts of 2-, 3- and 4-chloropyridine display a variety of
      anion stoichiometries and structures, including the rare [Hg(3)Cl(10)](4-)
      stoichiometry. 2-Chloropyridinium trichloromercurate(II), (I),
      (C(5)H(5)ClN)[HgCl(3)], monoclinic, P2(1)/n, a = 9.094 (8), b = 18.143 (4), c =
      12.902 (3) A, beta = 106.13 (4) degrees with Z = 8, has the [HgCl(3)](-)
      stoichiometry, but the anions are infinite chains composed of [HgCl(3)](-),
      HgCl(2) and Cl(-) moieties linked by longer Hg.Cl contacts. Hydrogen bonds link
      the cations to the formal Cl(-) ions. Tetrakis(3-chloropyridinium)
      decachlorotrimercurate(II), (II), (C(5)H(5)ClN)(4)[Hg(3)Cl(10)], monoclinic,
      P2(1)/n, a = 7.522 (2), b = 28.046 (3), c = 9.165 (2) A, beta = 105.78 (2)
      degrees with Z = 2, has the rare [Hg(3)Cl(10)](4-) stoichiometry and contains
      infinite one-dimensional double-stranded {([HgCl(4)](2-))(2) [HgCl(2)]}(n)
      anionic chains made up of linear HgCl(2) and distorted [HgCl(4)](2-) entities
      linked together by longer Hg.Cl contacts. The HgCl(2) moieties are joined by
      double [HgCl(4)](2-) bridges. Hydrogen bonds link the cations to the sides of the
      anionic columns. Tetrakis(4-chloropyridinium) decachlorotrimercurate(II), (III),
      (C(5)H(5)ClN)(4)[Hg(3)Cl(10)], triclinic, P1;, a = 9.907 (3), b = 13.226 (2), c =
      7.282 (2) A, alpha = 84.41 (2), beta = 74.81 (2), gamma = 87.34 (2) degrees with
      Z = 1, also has the [Hg(3)Cl(10)](4-) stoichiometry and the same type of
      {([HgCl(4)](2-))(2)[HgCl(2)]}(n) anionic chains that were found in compound (II),
      but the formal HgCl(2) and [HgCl(4)](2-) moieties are more discrete with much
      weaker contacts linking the individual units. Bifurcated hydrogen bonds with the
      cations cross-link the anionic chains to form an infinite two-dimensional
      network. Second forms of the 3- and 4-chloropyridinium salts were also obtained.
      3-Chloropyridinium trichloromercurate(II), (IV), (C(5)H(5)ClN)[HgCl(3)],
      monoclinic, P2(1)/c, a = 7.243 (5), b = 22.145 (8), c = 12.320 (3) A, beta =
      99.52 (3) degrees with Z = 8, has the [HgCl(3)](-) stoichiometry, but the anions
      are infinite chains composed of distorted [Hg(2)Cl(6)](2-) moieties. Bifurcated
      hydrogen bonds from the cations cross-link the anionic chains to form infinite
      two-dimensional layers. Bis(4-chloropyridinium) hexachlorodimercurate(II), (V),
      (C(5)H(5)ClN)(2)[Hg(2)Cl(6)], monoclinic, C2/m, a = 13.447 (3), b = 7.534 (2), c
      = 9.939 (2) A, beta = 97.48 (2) degrees with Z = 2, contains highly symmetrical
      discrete [Hg(2)Cl(6)](2-)anions. Bifurcated hydrogen bonds from the cations
      interconnect the anions to form infinite one-dimensional chains.

PMID- 10927384
TI  - The geometry and structural properties of the 4,8,12-trioxa-4,8,12,12c
      tetrahydrodibenzo
AB  - The geometry of the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrene
      system in the cationic state was established by X-ray structural resolution of
      the salts formed between the cation and various anions. The geometry was found to
      be planar for the 4,8,12-trioxa-4,8,12,12c-tetrahydrodibenzo[cd,mn]pyrenylium and
      2,6,10-tri(tert-butyl)-4,8,12-trioxa-4,8,12,12c
      tetrahydrodibenzo[cd,mn]pyrenylium cations with the monovalent anions I(-),
      BF(4)(-), PF(6)(-), AsF(6)(-), HNO(3).NO(3)(-) and CF(3)SO(3)(-), and the
      divalent anions S(2)O(6)(2-) and Mo(6)Cl(14)(2-). The salts were found to
      crystallize in distinct space groups following a characteristic pattern. Mixed
      cation-anion stacking resulted in space groups with high symmetry: Pbca in three
      cases and R3;c in one; a temperature study of the latter was made at ten
      different temperatures. The formation of dimers of anions and cations resulted in
      lower-symmetry space groups, mainly monoclinic (P2(1)/n, P2(1)/c and C2/c), but
      also P1;.

PMID- 10927385
TI  - Molecular aggregation in crystalline 1:1 complexes of hydrophobic D- and L-amino
      acids. I. The L-isoleucine series.
AB  - The amino acid L-isoleucine has been cocrystallized with seven selected D-amino
      acids including D-methionine [L-isoleucine-D-methionine (1/1),
      C(6)H(13)NO(2).C(5)H(11)NO(2)S, amino-acid side chain R = -CH(2)-CH(2)-S-CH(3)]
      and a homologous series from D-alanine [L-isoleucine-D-alanine (1/1),
      C(6)H(13)NO(2).C(3)H(7)NO(2), R = -CH(3)] through D-alpha-aminobutyric acid [L
      isoleucine-D-alpha-aminobutyric acid (1/1), C(6)H(13)NO(2).C(4)H(9)NO(2), R = 
      CH(2)-CH(3)] and D-norvaline [L-isoleucine-D-norvaline (1/1),
      C(6)H(13)NO(2).C(5)H(11)NO(2), R = -CH(2)-CH(2)-CH(3)] to D-norleucine [L
      isoleucine-D-norleucine (1/1), C(6)H(13)NO(2).C(6)H(13)NO(2), R = -CH(2)-CH(2)
      CH(2)-CH(3)] with linear side chains, and D-valine [L-isoleucine-D-valine (1/1),
      C(6)H(13)NO(2).C(5)H(11)NO(2), R = -CH-(CH(3))(2)] and D-leucine [L-isoleucine-D
      leucine (1/1), C(6)H(13)NO(2).C(6)H(13)NO(2), R = -CH(2)-CH-(CH(3))(2)] with
      branched side chains. All the crystal structures are divided into distinct
      hydrophilic and hydrophobic layers. In the five complexes with amino acids with
      linear side chains the polar parts of the D- and L-amino acids are related by
      pseudo-glide-plane symmetry, and four of them have remarkably similar molecular
      arrangements. The D-valine and D-leucine complexes, on the other hand, are
      structurally quite different with the polar parts of the D- and L-amino acids
      related by pseudo-inversion. Differences in the hydrogen-bond pattern in the two
      molecular arrangements are discussed.

PMID- 10927386
TI  - 3(5),4-Dimethyl- and 3,4,5-trimethylpyrazole at 200 K. X-ray crystallography and
      quantum-chemical analysis.
AB  - The crystal and molecular structures of 3(5),4-dimethylpyrazole, C(5)H(8)N(2),
      (I), and of 3,4,5-trimethylpyrazole, C(6)H(10)N(2), (II), have been determined at
      200 K. In (I) the 4,5-dimethylpyrazole tautomer is present in the solid state and
      the six independent molecules in the asymmetric unit form trimers via NH.N
      hydrogen bonds related by a pseudo centre of symmetry. The asymmetric unit of
      (II) contains one and a half molecules: these exhibit NH proton disorder and are
      hydrogen bonded to each other via their respective NH groups to form chains. Ab
      initio calculations at HF and B3LYP/6-31G** levels indicate that the 3,4
      dimethylpyrazole tautomer is more stable than the 4,5-dimethylpyrazole tautomer
      by only approximately 0.5 kcal mol(-1) (1 kcal mol(-1) = 4.184 kJ mol(-1)).

PMID- 10927387
TI  - Phase-transition-induced twinning in the 1:1 adduct of hexamethylenetetramine and
      azelaic acid.
AB  - The title compound, C(6)H(12)N(4).C(9)H(16)O(4), undergoes several thermotropic
      phase transitions. The crystalline structure is layered, with sheets of azelaic
      acid linked to sheets of hexamethylenetetramine by hydrogen bonds. In the room
      temperature phase, the azelaic acid molecules are disordered. By lowering the
      temperature, this disorder partially disappears. The ordering is clearly observed
      in reciprocal space where on the rods of diffuse scattering, present in the room
      temperature phase, a series of superstructure reflections emerges. This phase
      transition leads to twin-lattice quasi-symmetry (TLQS) twinning. The structure of
      this twinned phase is explored in this paper. There are two orientational domains
      linked by a mirror plane which relates disordered orientations of the acid
      molecules above the phase transition. A single domain has space group P2_1/c. The
      structure has been solved and refined on the complete set of data to R(1) =
      0.0469. The chains remain partially disordered, showing two acid groups with
      unequal population: the major form corresponding to a carboxylic acid and the
      minor to a carboxylate. The ordering of the structure, when going through the
      phase transition, is interpreted in terms of stabilization by C-H.O hydrogen
      bonding. A least-squares estimator of the twinning volume ratio is developed that
      gives an expression for the twinning ratio in terms of the intensities of
      nonoverlapping reflections. The twinning ratio obtained in the structure
      refinement compares very well with that obtained from this estimator.

PMID- 10927388
TI  - Structures des phases paraelectrique et ferroelectrique de Pb2KNb5O15.
AB  - The paraelectric and the ferroelectric/ferroelastic structures of
      Pb(2)KNb(5)O(15) have been refined by the Rietveld method from neutron and X-ray
      powder diffraction data. The paraelectric phase is tetragonal (space group
      P4/mbm) with lattice parameters a(t) = 12.646 (1) and c(t) = 3.9551 (2) A at 790
      K. The Pb- and K-atom distribution has been determined. It was established that
      the Pb atoms situated on the 15-coordinate sites are not on the special position
      (2mm) but are distributed over two disordered positions as in the tetragonal
      phase of Pb(2)KTa(5)O(15). The ferroelectric/ferroelastic phase is orthorhombic.
      The space group of the average structure is Cm2m and the lattice parameters are
      a(o) = 17.779 (2), b(o) = 18.015 (2), c(o) = 3.9209 (4) A at 294 K and a(o) =
      17.756 (1), b(o) = 18.019 (1), c(o) = 3.9141 (2) A at 81 K. It is isostructural
      with the average ferroelectric/ferroelastic structure of PbNb(2)O(6). The
      orthorhombic distortion is of the same order but the Curie temperature is lowered
      by the substitution 2K(+)-Pb(2+). The structures of PbNb(2)O(6), PbTa(2)O(6),
      Pb(2)KNb(5)O(15) and Pb(2)KTa(5)O(15) are compared. The ferroelectric
      polarization of the niobates is due to both the Pb off-site position and the Nb
      displacements, which induce a distortion of the oxygen lattice. In PbTa(2)O(6),
      the oxygen-lattice distortion is very weak. The polarization seems to be due only
      to the Pb atom. In the tantalates the substitution 2K(+)-Pb(2+) should weaken the
      correlations between the Pb atoms and consequently suppress the ferroelectric
      transition. Only a local polarization should take place; this might be the origin
      of the dielectric relaxation observed in this compound.

PMID- 10927389
TI  - Cluster configurations in modulated EuVxMo8+/-yO14 crystals.
AB  - Three orthorhombic crystals of chemical formula Eu(x)V(y)Mo(8+/-z)O(14) were
      investigated by X-ray diffraction (Mo Kalpha radiation, lambda = 0.71073 A). They
      have nearly the same lattice parameters (a approximately 11.3, b approximately
      10.0, c approximately 9.2 A), display one-dimensional incommensurate modulations
      of wavevector q* = gammac* and are characterized by the same superspace group
      Cmca(00gamma)s00. The crystals differ both in their compositions (namely
      Eu(0.976(6))V(1.13(5))Mo(7.10(5))O(14), Eu(0.986(4))V(1.10(3))Mo(7.30(1))O(14)
      and EuMo(7.96(1))O(14)) and in their gamma components [0.195 (2), 0.245 (2) and
      0.286 (3), respectively]. The average structures of these crystals appear closely
      related to the structures of LaMo(7.7)O(14) (not modulated) and LaMo(8)O(14)
      (modulated); however, two main differences are outlined: first, the modulation
      direction is c in the Eu-containing crystals but b in the modulated La-containing
      crystal [q* = (1/3)b*], second, the Eu-containing crystals have centrosymmetric
      structures while the La-containing crystals have polar structures (space group
      C2ca). The Mo (or Mo and V) atoms are stacked to form (001) layers of metallic
      clusters. The density modulation of these structures implies the existence of the
      new types of clusters Mo(9), Mo(10), Mo(6)V(4), Mo(7)V(3) and Mo(8)V(2) besides
      the clusters M(8) (Mo(8), Mo(6)V(2) and Mo(7)V) and M(7) (Mo(7) and Mo(6)V) which
      are already known. Mo(8) units with cis and trans configurations and Mo(6)V(2)
      units with a trans configuration appear as the main cluster types in these
      crystals. The nature of the metallic clusters changes along c, but inside one
      (001) layer it is likely that only one cluster type with a given configuration is
      present. The main structural result is the formation, in some unit cells, of
      strong intercluster Mo-Mo, Mo-V or V-V bonds with distances close to 2.6 A within
      a layer as well as between two neighbouring layers.

PMID- 10927390
TI  - Crystal structure, compressibility and possible phase transitions in
      ?boldvarepsilon-FeSi studied by first-principles pseudopotential calculations.
AB  - An investigation of the relative stability of the FeSi structure and of some
      hypothetical polymorphs of FeSi has been made by first-principles pseudopotential
      calculations. It has been shown that the observed distortion from ideal sevenfold
      coordination is essential in stabilizing the FeSi structure relative to one of
      the CsCl type. Application of high pressure to FeSi is predicted to produce a
      structure having nearly perfect sevenfold coordination. However, it appears that
      FeSi having a CsCl-type structure will be the thermodynamically most stable phase
      for pressures greater than 13 GPa. Fitting of the calculated internal energy vs
      volume for the FeSi structure to a third-order Birch-Murnaghan equation of state
      led to values, at T = 0 K, for the bulk modulus, K(0), and for its first
      derivative with respect to pressure, K(0)', of 227 GPa and 3.9, respectively.

PMID- 10927391
TI  - Systematic prediction of new inorganic ferroelectrics in point group 4.
AB  - The latest release of the Inorganic Crystal Structure Database contains a total
      of 87 entries corresponding to 70 different materials in point group 4. The
      structures reported for 11 materials in space group P4 satisfy the criteria for
      ferroelectricity, as do four in P4(1), one each in P4(2) and P4(3), 12 in I4,
      including seven that form three families, and another three in I4(1). Three
      previously known ferroelectrics were also listed in I4 and one in I4(1). In
      addition, the listing for point group 4 contains 22 entries for nonferroelectric
      materials and three with misassigned space groups. Among the newly predicted
      ferroelectrics in point group 4, assuming the validity of the underlying
      structural reports, are Ce(5)B(2)C(6), modulated NbTe(4), Na(3)Nb(12)O(31)F,
      Ca(2)FeO(3)Cl, K(4)CuV(5)O(15)Cl, TlBO(2), CrOF(3), PbTeO(3),
      VO(HPO(3))(H(2)O).3H(2)O, MgB(2)O(OH)(6), beta-tetragonal boron, CuBi(2)O(4),
      WOBr(4), Na(8)PtO(6), SbF(2)Cl(3), Ba(1.2)Ti(8)O(16), Ni[SC(NH(2))(2)](4)Cl(2),
      Ca(2)SiO(3)Cl(2), the mineral caratiite, NbAs, beta-NbO(2) and Ag(3)BiO(3).

PMID- 10927392
TI  - A TEM study of long-period mica polytypes: determination of the stacking sequence
      of oxybiotite by means of atomic resolution images and Periodic Intensity
      Distribution (PID).
AB  - In this study it is shown that the stacking sequences in long-period mica
      polytypes (including a rare example of a mixed-rotation polytype, with a 36-layer
      long periodicity) can be unambiguously determined using atomic resolution images
      recorded down two zone axes separated by 30 degrees (e.g. [100] and [31;0]) at
      the same area. Uniformity of these stacking sequences in a large area is further
      confirmed by the correspondence between computed and observed Periodic Intensity
      Distributions (PIDs) in electron diffraction patterns. The appearance of long
      period polytypes containing layers with different orientation parity may be
      explained by the coalescence of two small crystals during crystal growth.

PMID- 10927393
TI  - Structure determination of lithium chloroacetate, lithium bromoacetate and
      lithium iodoacetate by powder diffraction.
AB  - Most halogenoacetates of alkali salts readily undergo a thermally induced
      polymerization reaction to poly-(hydroxyacetic acid) in the solid state. The
      lithium salts represent a remarkable exception. The crystal structures of lithium
      chloroacetate, lithium bromoacetate and lithium iodoacetate were determined ab
      initio from synchrotron powder diffraction data. The three compounds are
      isostructural and differ considerably from the structures of sodium chloroacetate
      and silver chloroacetate, two compounds that undergo polymerization. Most likely,
      the strong polarizing effect of the small lithium cation is responsible for the
      unfavorable crystal structure in which each lithium cation is coordinated to four
      O atoms from four different halogenoacetate molecules. Lithium chloroacetate: a =
      9.3882 (9), b = 4.8452 (4), c = 9.0119 (7) A, beta = 94.330 (5) degrees; lithium
      bromoacetate: a = 9.7165 (11), b = 4.8610 (6), c = 9.0228 (11) A, beta = 93.946
      (5) degrees; lithium iodoacetate: a = 10.1812 (10), b = 4.8922 (8), c = 9.0468
      (10) A, beta = 93.251 (5) degrees, all crystallizing in space group P2(1)/c with
      Z = 4.

PMID- 10927394
TI  - Single-crystal structure analysis of a novel aryl phosphinate diglycidyl ether.
AB  - The crystal structure of 10-[2,5-bis(2,3-epoxy-1-propoxy)phenyl]-9-oxa-10
      phosphaphenanthren-10-one has been studied by single-crystal X-ray diffraction.
      The unit cell of C(24)H(21)O(6)P, M(r) = 436.4, is triclinic, P1;, with a = 8.507
      (3), b = 10.613 (4), c = 12.457 (3) A, alpha = 80.05 (3), beta = 71.38 (2), gamma
      = 76.69 (3) degrees, V = 1031.1 (6) A(3), Z = 2, D(x) = 1.406 Mg m(-3) and u(Mo
      Kalpha) = 0.17 mm(-1). The final R (wR) is 0.063 (0.057) {w = 1/[sigma(2)(F) +
      0.0004F(2)]} for 3619 unique reflections measured at 295 K. The aryl phosphinate
      group bonded to the central phenyl ring comes close to one of the two glycidyl
      ether groups, the epoxide ring of which is ordered. The epoxide ring far from the
      aryl phosphinate group is disordered. The NMR chemical shifts of the protons of
      the glycidyl ether group close to the aryl phosphinate group are reduced by the
      'ring-current effect'.

PMID- 10927395
TI  - Packing similarities of three isosteric molecules: 4,5-dichlorophthalic
      anhydride, 4,5-dibromophthalic anhydride and 5,6-dichlorobenzfurazan 1-oxide,
      including three polymorphs of 5,6-dichlorobenzfurazan 1-oxide.
AB  - 4,5-Dichlorophthalic anhydride (CPA) lies on a twofold axis in space group C2/c;
      the molecules pack as stacks of two-dimensional sheets. Polymorph A of 5,6
      dichlorobenzfurazan 1-oxide (CBF; systematic name 5,6-dichloro-2,1,3
      benzoxadiazole 1-oxide) is isomorphous with CPA with disordered CBF molecules
      being pseudo-isosteric with the CPA molecule. Polymorph C of CBF has similar unit
      cell dimensions but the arrangement of the molecules in the cell is different.
      4,5-Dibromophthalic anhydride occurs in space group P1; in a structure derived
      from the CPA structure. The four structures all have similar two-dimensional
      sheets of molecules, but differ, in addition to the disorder of the CBF
      molecules, in the stacking of successive sheets. There are three polymorphs of
      5,6-dichlorobenzfurazan 1-oxide. In all three the molecules are disordered about
      twofold or pseudo-twofold axes. In all three the molecules form chains involving
      similar Cl.O contacts along the direction of the twofold axis. In polymorphs A
      and C these chains form virtually identical two-dimensional sheets with inter
      chain C-H.O, C-H.N and Cl.Cl contacts, but with different stacking arrangements
      between the sheets. In polymorph B the chains are associated in face-to-face
      pairs with the same face-to-face overlap as in A, at an average distance of 3.42
      A compared to an average distance of 3.38 A in A (cf. Table 8); there are no two
      dimensional sheets.

PMID- 10927396
TI  - Modelling the crystal structure of the 2-hydronitronylnitroxide radical (HNN):
      observed and computer-generated polymorphs.
AB  - The crystal structures of two polymorphs of 4,4,5,5-tetramethyl-4,5-dihydro-1H
      imidazol-1-oxyl 3-oxide (the 2-hydronitronylnitroxide radical, HNN) are analyzed
      by packing energy criteria. Other unobserved polymorphic crystal structures are
      generated using a polymorph predictor package and three different force fields,
      one of which is without explicit Coulomb-type terms. The relative importance of
      several structural motifs (hydrogen-bonded dimers, shape-interlocking dimers or
      extended hydrogen-bonded chains) is discussed. As usual, many crystal structures
      within a narrow energy range are generated by the polymorph predictor, confirming
      that ab initio crystal-structure prediction is still problematic. Comparisons of
      powder patterns generated from the atomic coordinates of the X-ray structure and
      from computational crystal structures confirm that although the energy ranking
      depends on the force field used, the X-ray structure of the alpha polymorph was
      found to be among the most stable ones produced by the polymorph predictor, even
      using the chargeless force field.

PMID- 10927397
TI  - Crystal and molecular structures of 2-
AB  - The crystal and molecular structures of 2-[1-(2-aminoethyl)-2
      imidazolidinylidene]-2-nitroacetonitrile [C(7)H(11)N(5)O(2); space group P2(1)/n;
      Z = 4; a = 7.4889 (8), b = 17.273 (2), c = 7.4073 (8) A, beta = 111.937 (6)
      degrees ], (I), and 2,6-diamino-5-hydroxy-3-nitro-4H-pyrazolo[1,5-a]pyrimidin-7
      one monohydrate [C(6)H(6)N(6)O(4).H(2)O; space group P2(1)/n; Z = 4; a = 17.576
      (3), b = 10.900 (2), c = 4.6738 (6) A, beta = 92.867 (8) degrees ], (II), have
      been determined from X-ray, synchrotron and neutron powder diffraction data using
      various methods. The structures were originally solved from Guinier photographs
      with a grid search procedure and the program MRIA using a priori information from
      NMR and mass spectra on the possible geometry of the molecules. Because the
      conformation of molecule (I) changed during the bond-restrained Rietveld
      refinement, solvent water was found in (II) and, moreover, as both Guinier
      patterns were corrupted by texture, high-resolution texture-free synchrotron data
      were collected at the BM16 beamline, ESRF, to confirm the original results. Using
      the set of |F|(2) values derived from the synchrotron patterns after full-pattern
      decomposition procedures, the structures of (I) and (II) were solved by direct
      methods via SHELXS96, SIRPOW.92 and POWSIM without any preliminary models of the
      molecules, and by Patterson search methods via DIRDIF96 and PATSEE with the use
      of rigid fragments from each of the molecules. The neutron patterns allowed (I)
      and (II) to be solved using the grid search procedure and correct initial models
      of the molecules including H atoms. The results obtained from powder patterns
      measured on different devices demonstrate the high level of reproducibility and
      reliability of various powder software and equipment, with a certain preference
      for synchrotron facilities.

PMID- 10927398
TI  - Topological analysis of the electron density in hydrogen bonds.
AB  - Topological analysis of the experimental electron density rho(r) in hydrogen
      bonding regions has been carried out for a large number of organic compounds
      using different multipole models and techniques. Relevant systematic
      relationships between topological properties at the critical points and the usual
      geometric parameters are pointed out. Results involving X-ray data only and joint
      X-ray and neutron data, as well as special hydrogen bonding cases (symmetric,
      bifurcated, peptide bonds, etc.) are included and analysed in the same framework.
      A new classification of hydrogen bonds using the positive curvature of the
      electron density at the critical point [lambda(3)(r(CP))] is proposed.

PMID- 10927399
TI  - Crystal engineering using bisphenols: interwoven ladders, sheet and framework
      structures in the binary adducts of 4,4'-sulfonyldiphenol with pyrazine (2/1),
      4,4'-bipyridyl (1/1), trans-1,2-bis(4-pyridyl)ethene (1/1), 1,2-bis(4
      pyridyl)ethane (1/1) and 4,4'-trimethylenedipyridine (1/1), and in 4,4'
      sulfonyldiphenol-4,4'-trimethylenedipiperidine-water (2/2/1).
AB  - The structures of six hydrogen-bonded adducts of 4,4'-sulfonyldiphenol with
      heteroaromatic amines have been determined. In 4,4'-sulfonyldiphenol-pyrazine
      (2/1) the pyrazine molecules lie across centres of inversion. The bisphenol
      molecules are linked into C(8) chains parallel to [100] by means of O-H.O=S
      hydrogen bonds, and antiparallel pairs of these chains are cross-linked by the
      pyrazine molecules, via O-H.N hydrogen bonds, to form molecular ladders
      containing R(6)(6)(50) rings between the rungs of the ladders. Each ladder is
      interwoven with two neighbouring ladders, thus producing a continuous two
      dimensional sheet. The structure of 4,4'-sulfonyldiphenol-4,4'-bipyridyl (1/1)
      consists of spiral C(2)(2)(21) chains parallel to [010] containing alternating
      bisphenol and bipyridyl molecules linked by O-H.N hydrogen bonds: these chains
      are linked by two types of C-H.O hydrogen bonds which form C(5) chains along
      [001] and C(2)(2)(10) chains along [101], thus generating two interconnected nets
      characterized in the one case by a chequerboard pattern of R(6)(6)(44) and
      R(6)(6)(52) rings, and in the other by a single type of R(6)(6)(46) ring. 4,4'
      Sulfonyldiphenol-trans-1,2-bis(4-pyridyl)ethene (1/1) [systematic name: 4,4'
      sulfonyldiphenol-trans-4,4'-vinylenedipyridine (1/1)] and 4,4'-sulfonyldiphenol
      1,2-bis(4-pyridyl)ethane (1/1) [systematic name: 4,4'-sulfonyldiphenol-trans-4,4'
      ethylenedipyridine (1/1)] are isomorphous: the 1,2-bis(4-pyridyl)ethene component
      exhibits orientational disorder, corresponding approximately to a 180 degrees
      rotation of ca 23% of the molecules about the N.N vector; in each compound the
      structure is built from C(2)(2)(23) chains of alternating bisphenol and
      bis(pyridyl) molecules connected by O-H.N hydrogen bonds, running parallel to
      [112] and generated by translation. The [112] chains are linked by C-H.O hydrogen
      bonds which generate C(2)(2)(12) chains parallel to [101], so forming a two
      dimensional net built from R(6)(6)(50) rings. The structure of 4,4'
      sulfonyldiphenol-4,4'-trimethylenedipyridine (1/1) consists of C(2)(2)(24) chains
      parallel to [100] generated by translation and consisting of alternating
      bisphenol and bis(pyridyl) molecules linked by O-H.N hydrogen bonds. Pairs of
      such chains are coiled together to form double helices, and pairs of such double
      helices, of opposite hand, are linked together by paired C-H.O hydrogen bonds in
      R(2)(2)(10) rings to form pairs of interwoven ladders in which the C(2)(2)(24)
      chains form the uprights and the R(2)(2)(10) rings form the rungs, between which
      are R(6)(6)(50) rings: an R(2)(2)(10) ring belonging to one ladder lies at the
      centre of an R(6)(6)(50) ring belonging to the other. 4,4'-Sulfonyldiphenol-4,4'
      trimethylenedipiperidine-water (2/2/1) is a salt,
      2C(13)H(27)N(2)(+).2C(12)H(9)O(4)S(-).H(2)O, containing two independent singly
      protonated diamine cations, two independent bisphenolate anions, and neutral
      water molecules. The two independent diamine cations are linked by N-H.N hydrogen
      bonds into C(2)(2)(24) chains running parallel to [001] and generated by
      translation, and each type of bisphenolate anion forms an independent spiral
      C(12) chain, also parallel to [001]. The three types of chain are linked by the
      water molecules: the two types of bisphenolate chain are linked by water
      molecules acting as double donors in O-H.O(-) hydrogen bonds in a C(6)(4)(32)
      chain parallel to [100], thus generating a two-dimensional net built from
      R(8)(6)(56) rings; the diamine chains are linked to these nets by means of N-H.O
      hydrogen bonds in which the water molecules act as acceptors and further hydrogen
      bonds, of N-H.O(-) and N-H.O=S types, link these two-dimensional nets into a
      continuous three-dimensional framework.

PMID- 10927400
TI  - Crystal engineering using bisphenols and trisphenols. Complexes with 1,10
      phenanthroline: hydrogen-bonded chains in adducts with 4,4'-biphenol (1/1) and
      4,4'-sulfonyldiphenol (2/3), pi-pi stacked chains in the (1/2) adduct with 4,4'
      thiodiphenol, and pairwise-interwoven nets in 1,1,1-tris(4-hydroxyphenyl)ethane
      1,10-phenanthroline-methanol (1/1/1).
AB  - In 4,4'-biphenol-1,10-phenanthroline (1/1) [systematic name: 4,4'-biphenyldiol
      1,10-phenanthroline (1/1)] the diphenol molecules lie across centres of inversion
      and the phenanthroline molecules lie across twofold rotation axes; the
      phenanthroline molecules act as chain-building units and the molecular components
      are linked into steeply zigzag C(16) chains parallel to [101] by means of O-H.N
      hydrogen bonds. In the structure of 4,4'-thiodiphenol-1,10-phenanthroline (1/2)
      the phenanthroline molecules act as chain-terminating units; the supramolecular
      aggregation is finite, with the bisphenol linked to each phenanthroline molecule
      by means of a single O-H.N hydrogen bond. pi-pi stacking interactions between the
      phenanthroline molecules in neighbouring hydrogen-bonded aggregates serve to link
      these aggregates into a continuous two-dimensional array. The phenanthroline
      molecules in 4,4'-sulfonyldiphenol-1,10-phenanthroline (2/3) play two roles:
      molecules in general positions act as chain-terminating units and are linked to
      the sulfonyldiphenol molecules by means of three-centre O-H.(N)(2) hydrogen
      bonds, while those lying across twofold rotation axes act as chain builders and
      are linked to two different sulfonyldiphenol molecules by means of a two-centre O
      H.N hydrogen bond in each case; the resulting U-shaped five-component aggregates
      are further linked by C-H.O=S hydrogen bonds into a C(3)(3)(17)[R(2)(2)(12)]
      'chain of rings' along [001]. In 1,1,1-tris(4-hydroxyphenyl)ethane-1,10
      phenanthroline-methanol (1/1/1) [systematic name: 4,4',4"-ethylidynetriphenol
      1,10-phenanthroline-methanol (1/1/1)] the phenanthroline molecules again act as
      chain-terminating units: the trisphenol molecules and the methanol molecules are
      linked by O-H.O hydrogen bonds into two-dimensional nets built from R(6)(6)(42)
      rings, and pairs of these nets are interwoven. The formation of each net utilizes
      two hydroxyl groups per trisphenol molecule as hydrogen-bond donors and the
      remaining hydroxyl group acts as donor to the phenanthroline molecule in a three
      centre O-H.(N)(2) hydrogenbond.

PMID- 10927401
TI  - The single-crystal structure of the organic superconductor betaCO-(BEDT-TTF)2I3
      from a powder grain.
AB  - Synchrotron radiation diffraction data have been collected at 200 K on a
      microscopic single crystal (dimensions 12 x 10 x 2 um) of the title compound,
      where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene, C(10)H(8)S(8). The
      quality of the diffraction data allowed a full structure refinement and enabled
      the determination of structural details such as the conformations of the ethylene
      groups as well as the occupancy of the triiodide sites. The compound was found to
      be slightly iodine-deficient and better described as beta(CO)-(BEDT-TTF)(2)I(3-x)
      [x = 0.014 (3)]. One of the ethylene groups of the BEDT-TTF cation is disordered
      at this temperature and exists in two distinct conformations with occupancies
      which are identical within the standard uncertainty.

PMID- 10927402
TI  - Absolute configurations of Emycin D, E and F; mimicry of centrosymmetric space
      groups by mixtures of chiral stereoisomers.
AB  - The crystal structures of Emycin E (1), di-o-bromobenzoyl-Emycin F (2) and o
      bromobenzoyl-Emycin D (3) have been determined by X-ray analysis at low
      temperature. Emycin E and o-bromobenzoyl-Emycin D both crystallize with two
      molecules in a triclinic unit cell. These two structures can be solved and
      refined either in the centrosymmetric space group P1;, with apparent disorder
      localized at or around the expected chiral centre, or in the non-centrosymmetric
      space group P1 as mixtures of two diastereomers without disorder. Only the latter
      interpretation is consistent with the chemical and spectroscopic evidence.
      Refinements in the centrosymmetric and non-centrosymmetric space groups are
      compared in this paper and are shown to favour the chemically correct
      interpretation, more decisively so in the case of the bromo derivative as a
      result of the anomalous dispersion of bromine. Structures (1) and (3) provide a
      dramatic warning of the dangers inherent in the conventional wisdom that if a
      structure can be refined satisfactorarily in both centrosymmetric and non
      centrosymmetric space groups, the former should always be chosen. In these two
      cases, despite apparently acceptable intensity statistics and R factors (5.87 and
      3.55%), the choice of the centrosymmetric space group leads to the serious
      chemical error that the triclinic unit cell contains a racemate rather than two
      chiral diastereomers! The weakest reflections are shown to be most sensitive to
      the correct choice of space group, underlining the importance of refining against
      all data rather than against intensities greater than a specified threshold. The
      use of similar-distance restraints is shown to be beneficial in both P1
      refinements. Di-o-bromobenzoyl-Emycin F crystallizes in the monoclinic space
      group P2(1) with one molecule in the asymmetric unit and so does not give rise to
      these problems of interpretation. The absolute configuration of the two bromo
      derivatives, and hence the Emycins in general, was determined unambiguously as S
      at the chiral centre C3.

PMID- 10927403
TI  - A mediated hydrogen bond in an alpha-hydroxycarboxyl group: X-ray structure of
      (R,R)-N-methyltartramic acid monohydrate and an ab initio study of model systems.
AB  - The crystal structure of (R,R)-N-methyltartramic acid monohydrate is presented
      and compared with that of the parent compound, (R,R)-tartaric acid. Despite some
      conformational differences between the two molecules the packing is very similar,
      as it is dictated by the carboxyl rather than the amide function. Particular
      attention is paid to a mediated three-centre hydrogen bond as one of the packing
      motifs involving the alpha-hydroxycarboxyl moiety. The stability and geometry of
      such structures in the gas phase and in solution are examined via theoretical ab
      initio methods using the RHF/6-311++G** and RHF/6-311++G**/Onsager models,
      respectively. Liquid media, in particular those of high polarity, are found to
      stabilize the structures considerably.

PMID- 10927404
TI  - Anhydrous ammonioguanidinium(2+) and dihydrated bis
AB  - An error in printing is reported. In the paper by Ross et al. [Acta Cryst.
      (1999), B55, 246-254] the length of a bond formed by H3 is given incorrectly in
      the sixth sentence of the first paragraph of section sign3.3 on page 251. The
      sentence should read 'The out-of-plane displacement modifies the hydrogen-bonding
      pattern, allowing an approach of 2.21 (2) A to F2, see Table 4; the resulting
      increase in structural stability supports this model.'

PMID- 10927405
TI  - Structural chemistry of vanadium oxides with open frameworks.
AB  - The present work is dedicated to a crystal-chemical and topographical analysis of
      vanadium oxides with open structures. The review covers, apart from a few
      exceptions, only pure vanadium oxide structures with vanadium in oxidation states
      greater than +3. Purely tetrahedral frameworks are not discussed because of their
      traditional, well known crystal chemistry and only a few examples of cluster
      compounds are provided. Structural classification and notation of vanadium oxide
      frameworks are proposed based on the following scheme: polyhedra --> chain -->
      layer --> three-dimensional framework. Thus, approximately 60 types of vanadium
      oxide frameworks are divided into five classes by type of coordination polyhedra
      present and into 14 subclasses by a more complex structural formation. Details
      are also given of the analysis of vanadium-oxygen coordination polyhedra and
      their metamorphosis: tetrahedron-trigonal bipyramid-square pyramid-octahedron, as
      well as the combinatorial deduction of possible structures for the most common
      framework types.

PMID- 10927406
TI  - Metal arrays in structural units based on anion-centered metal tetrahedra.
AB  - Structural units based on anion-centered metal tetrahedra (XA(4); X = O, N; A =
      metal) are described as eutactic metal fragments with anions in tetrahedral
      interstices. In this respect these units may be subdivided into fluorite
      derivatives and units based on stellae quadrangulae (tetrahedral stars). To
      describe the geometry of the metal arrays a set of tetrahedrally packed metal
      radii, r(tp), is derived for A = Cu, Pb, Bi, and some rare-earth metals from the
      systematic analysis of the A.A distances within (XA(4)) tetrahedra. Analysis of
      these radii and of the structural geometry of the units shows that the insertion
      of anions into tetrahedral interstices of the metal fragment causes its expansion
      and distortions by nonbonded anion-anion repulsions. The main effect is owing to
      the linkage of (XA(4)) tetrahedra via edges, which leads to compression of the
      shared A.A edges and stretching of the unshared edges. The geometry of this
      effect is described by some empirical expressions. It is suggested that the
      eutactic arrangement of metal atoms in structural units based on anion-centered
      metal tetrahedra is caused by the closed-shell metal-metal bonding interactions

PMID- 10927407
TI  - Crystal structure of moganite-type phosphorus oxynitride: relationship to other
      twinned-quartz-based structures.
AB  - The structure of moganite-type phosphorus oxynitride quenched from high-pressure
      high-temperature conditions has been refined using neutron powder diffraction
      data. This moganite-type structure, space group I2/a, Z = 12, is slightly less
      distorted with respect to the Imab aristotype than is moganite (a monoclinic form
      of silica). A close topological relationship has been identified between the
      moganite-type and orthorhombic BeH(2) structures indicating that SiO(2), PON and
      BeH(2) all adopt structures belonging to the twinned-quartz-based group. This
      group represents another possible structure type for systems composed of corner
      sharing AX(4) tetrahedra. Structures of this group are obvious candidates for
      intermediate phases between the cristobalite and quartz types.

PMID- 10927408
TI  - Total neutron diffraction: a route to the correct local structure of disordered
      LaMo2O5 and its application to the model compound Zn2Mo3O8.
AB  - Analysis of Bragg diffraction is the normal route to the structure of crystalline
      materials. Here we demonstrate the use of total neutron diffraction in
      determining the local structure in the disordered lanthanum molybdate
      LaMo(2)O(5). An average structure with space-group symmetry P6(3)/mmc accounts
      for the Bragg scattering and shows that the compound contains the rare Mo(6)O(18)
      cluster and a unique type of Mo-Mo bonded sheet. However, this gives an
      incomplete picture of the structure, since it does not reveal how the sites with
      fractional occupancy are occupied at a local level. Two models describing
      possible local structures are constructed by removing symmetry elements present
      in the average structure. Total correlation functions, T(r), calculated from
      these structures, with space-group symmetry P6(3)mc and P3;m1, are compared with
      the experimental T(r) to show the validity of these local structures. The close
      relationship between the T(r)'s of the component structures gives an insight into
      why disorder occurs in LaMo(2)O(5). The calculated and experimental T(r)'s for a
      model compound, Zn(2)Mo(3)O(8), are compared to show the agreement expected from
      an ordered crystalline material. Remaining discrepancies between our model and
      the experimental T(r) give an insight into the origin of additional disorder in
      LaMo(2)O(5).

PMID- 10927409
TI  - Long-range Coulomb forces and localized bonds.
AB  - The ionic model is shown to be applicable to all compounds in which the atoms
      carry a net charge and their electron density is spherically symmetric regardless
      of the covalent character of the bonding. By examining the electric field
      generated by an array of point charges placed at the positions of the ions in
      over 40 inorganic compounds, we show that the Coulomb field naturally partitions
      itself into localized regions (bonds) which are characterized by the electric
      flux that links neighbouring ions of opposite charge. This flux is identified
      with the bond valence, and Gauss' law with the valence-sum rule, providing a
      secure theoretical foundation for the bond-valence model. The localization of the
      Coulomb field provides an unambiguous definition of coordination number and our
      calculations show that, in addition to the expected primary coordination sphere,
      there are a number of weak bonds between cations and the anions in the second
      coordination sphere. Long-range Coulomb interactions are transmitted through the
      crystal by the application of Gauss' law at each of the intermediate atoms. Bond
      fluxes have also been calculated for compounds containing ions with non-spherical
      electron densities (e.g. cations with stereoactive lone electron pairs). In these
      cases the point-charge model continues to describe the distant field, but
      multipoles must be added to the point charges to give the correct local field.

PMID- 10927410
TI  - Structure of and electron density in RbTiOAsO4 at 9.6 K.
AB  - Structure factors for rubidium titanyl arsenate, RbTiOAsO(4), were measured with
      Mo Kalpha radiation (lambda = 0.71069 A) at 9.6 and 295 K. The data show that
      there is no phase transition between room temperature and 9.6 K. The space group
      is Pna2(1). Unit-cell parameters are a = 13.218 (1), b = 6.6500 (9) and c =
      10.761 (1) A at 9.6 K, and a = 13.261 (2), b = 6.6791 (8) and c = 10.769 (1) A at
      295 K. As the temperature was lowered from 295 to 9.6 K the Rb atoms moved along
      the c axis in the direction of the polarization vector, while no significant
      change was noted for the Ti-O-As network. Strong accumulation and polarization of
      the difference electron density (Deltarho) in exceptionally short covalent Ti-O
      bonds alternates with the depleted density in long Ti-O bonds. The Deltarho near
      the Ti atoms is polarized and aligned in the negative c direction in accordance
      with the ferroelectric properties of this material. However, the electron density
      near the Rb atoms is depleted in this direction and the excess Deltarho is moved
      further away from the nuclei along the c vector.

PMID- 10927411
TI  - Structure refinement of Cu8GeS6 using X-ray diffraction data from a multiple
      twinned crystal.
AB  - The structure of the orthorhombic room-temperature phase of Cu(8)GeS(6) (copper
      germanium sulfide), M(r) = 773.27, has been refined on the basis of X-ray
      diffraction data from a 12-fold twinned crystal applying a six-dimensional twin
      refinement technique. For 1804 unique reflections measured using Mo Kalpha
      radiation, R(F) was 0.083 with 77 structure parameters and 12 scale factors. The
      symmetry operations, the unit cell and other crystal data are (0, 0, 0; (1/2),
      (1/2), 0) + x, y, z; y, x, z; (1/4) - x, (3/4) - y, (1/2) + z; (3/4) - y, (1/4) -
      x, (1/2) + z; a = b = 9.9073 (3) A, c = 9.8703 (4) A, alpha = beta = 90 degrees,
      gamma = 90.642 (4) degrees; V = 968.7 (1) A(3), Z = 4, D(x) = 5.358 Mg m(-3), u =
      21.70 mm(-1). The standard setting of the space group and the reduced unit cell
      are Pmn2(1); a = 7.0445 (3), b = 6.9661 (3), c = 9.8699 (5) A; Z = 2.

PMID- 10927412
TI  - Synchrotron radiation study of yttria-stabilized zirconia, Zr0.758Y0.242O1.879.
AB  - The fluorite-related cubic structure of yttria-stabilized zirconia,
      Zr(0.75)(8)Y(0.24)(2)O(1.87)(9), has been studied by single-crystal X-ray
      diffraction using synchrotron radiation and by EXAFS. Two diffraction data sets
      obtained at X-ray energies of 512 and 10 eV below the Y K edge revealed that in
      the average structure Zr atoms are displaced from the origin of the space group
      Fm3;m along <111> by 0.19 A, while Y atoms reside at the origin. Approximately
      48% of the O atoms occupy the ideal position in the fluorite-type structure,
      while 43% of O atoms are displaced from the ideal position along <001> by 0.31 A.
      The remaining 9% of O atoms are presumably sited at interstitial positions. Local
      structures around Zr and Y are investigated by combining the results of single
      crystal X-ray diffraction and EXAFS studies.

PMID- 10927413
TI  - Correlation between structural parameters of garnet and garnet-like structures.
AB  - Statistical analysis of structural parameters of garnet and garnet-like
      structures retrieved from the Inorganic Crystal Structure Database has revealed
      strong correlations between them. The degree of correlation depends on doping
      site and garnet type. Structural parameters are not equally sensitive to changes
      imposed by doping. The strongest correlation exists between the unit-cell
      parameter and the doping-ion radius. In the case of doping at the dodecahedral
      sites, the most sensitive parameter is the shortest dodecahedral distance.
      Principal component analysis (PCA) clearly shows that the first component
      explains most of the variation of structural data. It has a geometric basis and
      correlates with the effective radii of the doping ion. Partial correlation helps
      to identify the strongest relations between pairs of variables when the influence
      of other structural variables on them is controlled. It appears that in some
      cases partial correlation has a different sign when compared with the results of
      the standard correlation technique.

PMID- 10927414
TI  - Application and comparison of different tests on twinning by merohedry.
AB  - Three different tests on twinning by merohedry from the literature have been
      applied to single-crystal data sets of five different inorganic crystal
      structures. Although the three test procedures differ significantly with regard
      to their efficiency, in both detecting the existence of twinning and estimating
      the volume fractions of the twin individuals, they represent useful tools in the
      early stages of a structure analysis and should be applied routinely in the
      preliminary stage of a structure determination whenever a twinning by merohedry
      is possible.

PMID- 10927415
TI  - Structure of
AB  - The crystal structure of the title compound, dimethylammonium
      tetrachlorocobaltate(II), has been determined at four temperatures between 297
      and 366 K, in order to investigate possible phase transitions at 313 and 353 K
      [Kapustianik, Polovinko & Kaluza et al. (1996). Phys. Status Solidi A, 153, 117
      122]. We found that there is no significant change either in the hydrogen-bonding
      network or in the cell parameters, apart from a linear dilatation with
      temperature. This study reveals that the anomalous variation in electric
      conductivity and some of the other physical properties of the compound cannot be
      explained by structural changes.

PMID- 10927416
TI  - Molecular co-crystals of 2-aminothiazole derivatives.
AB  - A series of molecular adducts of 2-aminothiazole derivatives - 2-aminothiazole, 2
      amino-2-thiazoline and 2-aminobenzothiazole with the carboxylic-acid-substituted
      heterocyclics indole-2-carboxylic acid, N-methylpyrrole-2-carboxylic acid and
      thiophene-2-carboxylic acid - have been prepared and characterized using X-ray
      powder diffraction and in five cases by single-crystal X-ray diffraction methods.
      These five compounds are the adducts of 2-amino-2-thiazolium with indole-2
      carboxylate [(C(3)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], and N-methylpyrrole-2
      carboxylate [(C(3)H(7)N(2)S)(+)-(C(6)H(6)NO(2))(-)], 2-aminobenzothiazolium with
      indole-2-carboxylate [(C(7)H(7)N(2)S)(+)(C(9)H(6)NO(2))(-)], N-methylpyrrole-2
      carboxylate [(C(7)H(7)N(2)S)(+)(C(6)H(6)NO(2))(-)] and thiophene-2-carboxylate
      [(C(7)H(7)N(2)S)(+)(C(5)H(3)O(2)S)(-)]. All complexes involve proton transfer, as
      indicated by IR spectroscopy, while the five crystal structures display similar
      hydrogen-bonding patterns with the dominant interaction being an R(2)(2)(8) graph
      set dimer association between carboxylate groups and the amine/heterocyclic
      nitrogen sites. Futhermore, in each case a subsiduary interaction between an
      amino proton and a carboxylate oxygen completes a linear hydrogen-bonded chain.
      In addition to this, the indole-2-carboxylate molecules in the adduct structure
      with 2-amino-2-thiazolium form associated dimers which add to the hydrogen
      bonding network.

PMID- 10927417
TI  - X-ray and neutron diffraction study of benzoylacetone in the temperature range 8
      300 K: comparison with other cis-enol molecules.
AB  - The crystal structure of benzoylacetone (1-phenyl-1,3-butanedione,
      C(10)H(10)O(2); P2(1)/c, Z = 4) has been determined at 300, 160 (both Mo Kalpha X
      ray diffraction, XRD), 20 (lambda = 1.012 A neutron diffraction, ND) and 8 K (Ag
      Kalpha XRD), to which should be added earlier structure determinations at 300 (Mo
      Kalpha XRD and ND, lambda = 0.983 A) and 143 K (Mo Kalpha XRD). Cell dimensions
      have been measured over the temperature range 8-300 K; a first- or second-order
      phase change does not occur within this range. The atomic displacement parameters
      have been analyzed using the thermal motion analysis program THMA11. The most
      marked change in the molecular structure is in the disposition of the methyl
      group, which has a librational amplitude of approximately 20 degrees at 20 K and
      is rotationally disordered at 300 K. The lengths of the two C-O bonds in the cis
      enol ring do not differ significantly, nor do those of the two C-C bonds, nor do
      these lengths change between 8 and 300 K. An ND difference synthesis (20 K) shows
      a single enol hydrogen trough (rather than two half H atoms), approximately
      centered between the O atoms; analogous results were obtained by XRD (8 K). It is
      inferred that the enol hydrogen is in a broad, flat-bottomed single-minimum
      potential well between the O atoms, with a libration amplitude of approximately
      0.30 A at 8 K. These results suggest that at 8 K the cis-enol ring in
      benzoylacetone has quasi-aromatic character, in agreement with the results of
      high-level ab initio calculations made for benzoylacetone [Schiott et al. (1998).
      J. Am. Chem. Soc. 120, 12117-12124]. Application [in a related paper by Madsen et
      al. (1998). J. Am. Chem. Soc. 120, 10040-10045] of multipolar analysis and
      topological methods to the charge density obtained from the combined lowest
      temperature X-ray and neutron data provides evidence for an intramolecular
      hydrogen bond with partly electrostatic and partly covalent character, and large
      p-delocalization in the cis-enol ring. This is in good agreement with what is
      expected from the observed bond lengths. Analysis of the total available (through
      the Cambridge Structural Database, CSD) population of cis-enol ring geometries
      confirms earlier reports of correlation between the degree of bond localization
      in the pairs of C-C and C-O bonds, but does not show the dependence of bond
      localization on d(O.O) that was reported earlier for a more restricted sample. It
      is suggested that the only reliable method of determining whether the enol
      hydrogen is found in a single or double potential well is by low-temperature X
      ray or (preferably) neutron diffraction.

PMID- 10927418
TI  - On the polymorphism of a sapogenin monohydrate induced by different rotations of
      water molecules.
AB  - The structure of 1beta,3beta,11alpha-trihydroxyspirosta-5,25(27)-diene
      (C(27)H(40)O(5); a steroidal sapogenin) isolated from Helleborus serbicus Adam
      1906 (Ranunculaceae) and crystallized from absolute ethanol as a monohydrate
      (melting point 519-522 K) had been characterized by two symmetry-independent
      binary (steroid-water) layers, cross-linked by hydrogen bonds [Kalman et al.
      (1985). Acta Cryst. C41, 1645-1647]. Recently, a novel monohydrate was
      crystallized again from absolute ethanol (source: Helleborus multifidus
      subspecies serbicus) with a somewhat higher melting point of 525-526 K. X-ray
      analysis of these crystals [Argay et al. (1998). Acta Chim. Hung. 135, 449-456]
      revealed a novel polymorph (hereinafter denoted polymorph B), which is also built
      up by two binary layers of C(27)H(40)O(5) and H(2)O, but in which the relative
      position of these layers differs from that found in the first modification
      (polymorph A). Comparing the two polymorphs, layers of one type are found to be
      similar, displaying identical hydrogen bonding, whereas layers of the second type
      differ with respect to the orientations adopted by the water molecules; these
      orientations also differ from those in the layers of the first type.
      Consequently, by these water rotations, hydrogen bonds, at least partly, are
      reversed. This leads to two different close packings: in form A four consecutive
      layers are cross-linked by two homomolecular (hydroxyl.hydroxyl and water.water)
      hydrogen-bond pairs, while in B there are only heteromolecular hydroxyl.water
      bonds. These hydrogen-bond dissimilarities together with the differences in the
      weak CH.X etc. interactions explain the greater stability of the higher melting
      point form B.

PMID- 10927419
TI  - Molecular structures and conformations of three 3-azabicyclononanes.
AB  - The structure, conformation, molecular geometry and the mode of packing of 7-tert
      butyl-N-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonane (C(25)H(33)N; MTABN), N
      acetyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonane (C(22)H(25)NO; AABN) and N-methyl
      2,4-bis(2-methylphenyl)-3-azabicyclo[3.3.1]nonan-9-ol (C(23)H(29)NO; MHABN) are
      presented. The compounds MTABN and MHABN crystallize in monoclinic space groups,
      whereas AABN is orthorhombic. In each of the three structures, the bicyclic ring
      system adopts a chair-chair conformation and the phenyl rings are in equatorial
      orientation with respect to the piperidine ring. In AABN, apart from the van der
      Waals forces, weak intermolecular C-H.O type interactions are involved in the
      packing.

PMID- 10927420
TI  - Investigation of the structural phase transitions near 190 K in 4,4'
      dichlorobenzophenone.
AB  - X-ray structure studies have been carried out on single crystals of 4,4'
      dichlorobenzophenone at temperatures from 164 to 295 K. The structure determined
      at 164 K is monoclinic I2/c. Crystal data: T = 164 K; a = 24.527 (6), b = 6.064
      (1), c = 7.457 (4) A; beta = 100.10 (2) degrees; V = 1091.9 (6) A(3); Z = 4; d(c)
      = 1.528 g cm(-3); lambda(Mo Kalpha) = 0.71073 A; u = 0.565 mm(-1); F(000) = 512;
      R = 0.04. The temperature dependence of the unit-cell parameters and of the
      intensities of some symmetry-sensitive reflections has been measured over the
      range 164-293 K, both in warm-up and cool-down experiments. It has been
      established that the phase transformation between the C2/c and I2/c structures
      occurs as a sequence of two closely spaced first-order phase transitions. In
      between these phase transitions the crystal is in an intermediate state whose
      structure is different from both C2/c and I2/c. The experimental data give us
      ground to suppose that the intermediate state is disordered, having a primitive
      cell half as large as in the two ordered phases. Within the temperature interval
      where the said intermediate state exists the thermal expansivity along axis c is
      negative.

PMID- 10927421
TI  - Structural metrics relationships in covalently bonded organic azides.
AB  - Geometrical parameters of covalently bonded organic azides have been analysed
      using X-ray structural data retrieved from the Cambridge Structural Database. The
      RNNN fragment geometry shows some important general features: (i) a preference
      for a trans C(s) configuration; (ii) bending of the N-N-N unit; (iii)
      substantially different N-N bond lengths in the azide group. Electron-density
      redistribution within the covalently bonded azide group (relative to that in the
      isolated azide anion) promotes the capacity of the terminal azide N atom to form
      hydrogen bonds.

PMID- 10927423
TI  - Metastructures: homeomorphisms between complex inorganic structures and three
      dimensional nets.
AB  - We propose a general approach to nets and structures in which vertices represent
      stereochemically significant groups or clusters of atoms, and edges represent the
      linkage between these groups. Vertices may be single atoms, dimers, coordination
      polyhedra, clusters of atoms or clusters of coordination polyhedra; edges may be
      single chemical bonds or sets of several chemical bonds. Thus, a single net may
      be the basis for a family of structures that are homeomorphic to that net. The
      coordination of polyhedra or units around a vertex is visualized by connecting
      the centres of the atoms or groups at the vertices connected with the central
      vertex. Thus, the concept of coordination number is extended to include
      coordinating groups. We name a net after a homeomorphic simple structure-type for
      which there is a one-to-one correspondence between the vertices of the net and
      specific atoms of the structure, and between the edges of the net and the
      chemical bonds. We term the resulting more complex structures metastructures in
      order to distinguish them from their corresponding simple structure-types.
      Individual metastructures are referred to as alpha structures similar to a
      particular simple type. Thus, the open complex framework of [V(5)O(9)(PO(4))(2)]
      composition in microporous Na(v)[((V(4+)(4
      w)V(5+)(1+w))O(9))(PO(4))(2)].(PO(4))(x).(OH)(y).zH(2)O is an alpha-NbO structure
      based on the simple net that is homeomorphic to NbO. This approach is effective
      in hierarchically classifying both simple close-packed structures and very
      complicated microporous structures.

PMID- 10927424
TI  - Charge density in NiCl2.4H2O at 295 and 30 K.
AB  - The charge distribution has been determined by multipole refinements against
      single-crystal X-ray diffraction data. In the refinements a comparison was made
      between the densities based on H-atom parameters from X-ray and neutron data,
      respectively. X-ray study: lambda(Mo Kalpha) = 0.71073 A, F(000) = 408; at 30 K:
      R(F) = 0.015 for 6686 reflections; at 295 K: R(F) = 0.022 for 4630 reflections.
      The nickel ion is octahedrally surrounded by four water molecules and two
      chloride ions, forming a locally neutral Ni(H(2)O)(4)Cl(2) complex. Two of the
      water molecules are coordinated to nickel approximately in one of the tetrahedral
      ('lone-pair') directions; the other two are trigonally coordinated. At 30 K one H
      atom in one of the trigonally coordinated water molecules is disordered, with
      equal occupation of two different positions. Owing to the polarizing influence of
      the nickel ion there are two peaks in the lone-pair plane of the water molecules
      when these are tetrahedrally coordinated; for those trigonally coordinated there
      is just one peak. The individual ('partial') charge densities, calculated from
      the deformation functions of only nickel or the separate water molecules, have
      also been calculated to study the effects of superposition of the individual
      densities. In the individual density of nickel an excess is observed in the
      diagonal directions and a deficiency in the ligand directions. However, owing to
      the influence of the whole crystalline environment, the maxima around nickel are
      not found in the planes defined by nickel and the six ligands.

PMID- 10927425
TI  - Determination of the modulated structure of Sr14/11CoO3 through a (3 + 1)
      dimensional space description and using non-harmonic ADPs.
AB  - Sr(14/11)CoO(3) (i.e. Sr(14)Co(11)O(33), tetradecastrontium undecacobalt
      tritriacontaoxide), a new phase in the hexagonal perovskite Sr(x)CoO(3) system,
      has been prepared and its structure solved from single-crystal X-ray data within
      the (3 + 1)-dimensional formalism. Sr(14/11)CoO(3) crystallizes in the trigonal
      symmetry, R3;m(00gamma)0s superspace group with the following lattice parameters:
      a(s) = 9.508 (2), c(s) = 2.5343 (7) A, q = 0.63646 (11)c(*) and V(s) = 198.40
      (13) A(3). With the commensurate versus incommensurate test not being conclusive,
      the structure was considered as commensurate (P32 three-dimensional space group),
      but refined within the (3 + 1)-dimensional formalism to a residual factor R =
      0.0351 for 47 parameters and 1169 independent reflections. Crenel functions were
      used for the oxygen and cobalt description and a Gram-Charlier expansion up to
      the third order of the atomic displacement parameter was employed for one Co
      atom. The structure is similar to that of Sr(6/5)CoO(3), but with a different
      sequence of the octahedra and trigonal prism polyhedra along the [CoO(3)] chains.
      An interesting feature evidenced by the non-harmonic expansion is the
      displacement of the prismatic Co atoms from the site center, towards the prism
      rectangular faces.

PMID- 10927426
TI  - The crystal structure of Tm5Re2O12.
AB  - The crystal structure of Tm(5)Re(2)O(12), pentathulium dirhenium dodecaoxide, was
      determined by synchrotron diffraction on a reticular merohedral twin, revealing
      space group C2/m with a = 12.3717 (7), b = 5.6744 (3), c = 7.4805 (4) A, beta =
      107.816 (2) degrees and Z = 2. Distorted ReO(6) octahedra form chains with
      alternating rhenium-rhenium distances of 2.455 (1) and 3.219 (1) A. Early reports
      on Ln(2)ReO(5) compounds are critically reviewed in the light of our results for
      Tm(5)Re(2)O(12).

PMID- 10927427
TI  - Symmetry classification of the layered perovskite-derived AnBnX3n+2 structures.
AB  - The effects of combinations of octahedral tilts on the symmetries of layered
      A(n)B(n)X(3n+2) structures were considered. Two complementary approaches were
      used to deduce the symmetries. The space groups associated with different tilt
      systems were determined for structures with different layer thicknesses (n
      values) and for structures with different layer stacking arrangements. For the
      most symmetrical tilts about the orthorhombic axes of the A(n)B(n)X(3n+2)
      structure, maximal group/subgroup relations were established. Comparison of these
      results with experimental data available in the literature suggests that the
      symmetries of most observed A(n)B(n)X(3n+2) compounds are fully determined by the
      tilt systems adopted by rigid BX(6) octahedra. The most common tilt system
      observed at room temperature is a combination of an in-phase tilt about an
      orthorhombic axis parallel to the pseudo-fourfold axis of the octahedron with a
      tilt about an orthorhombic axis perpendicular to the layers.

PMID- 10927428
TI  - The use of CCD area detectors in charge-density research. Application to a
      mineral compound: the alpha-spodumene LiAl(SiO3)2.
AB  - X-ray diffraction data sets collected on both Nonius and Siemens (Bruker)
      goniometers equipped with charge-coupled device (CCD) area detectors have been
      tested for the electron-density determination of the aluminosilicate mineral
      compound alpha-spodumene LiAl(SiO(3))(2), aluminium lithium silicon oxide. Data
      collection strategies, reflection intensity peak integration methods and
      experimental error estimates are different for the two instruments. Therefore,
      the consistency and quality of the two types of CCD measurements have been
      carefully compared to each other and to high-resolution data collected on a
      conventional CAD-4 point-detector diffractometer. Multipole density model
      refinements were carried out against the CCD data and the statistical factors
      analysed in terms of experimental weighting schemes based on the standard
      uncertainties of the diffraction intensities derived by the Nonius and Siemens
      software programs. Consistent experimental electron-density features in the Si-O
      Si and Si-O-Al bridges were found from both CCD data sets. The net atomic charges
      obtained from the kappa refinements against each CCD data set are also in good
      agreement and quite comparable with the results of the conventional CAD-4
      experiment.

PMID- 10927429
TI  - Crystal morphology prediction and morphology variation in NaIO4 and NaIO4.3H2O.
AB  - Attachment energies computed with only Coulomb potentials have been utilized to
      predict crystal morphologies for NaIO(4), sodium iodate, and the hydrate
      NaIO(4).3H(2)O, sodium iodate trihydrate [actually Na(H(3)O)(IO(3))(OH)(3)]. As
      with other previously studied water-soluble ionic compounds, these two systems
      exhibit a systematic relationship between the early growth morphology and that of
      mature crystals; this relationship can in each case be reproduced by adjusting
      one attachment energy value. Morphology prediction for these two substances is of
      particular interest because NaIO(4).3H(2)O is a polar crystal and involves
      extensive hydrogen bonding, and because obtaining the observed morphology for
      NaIO(4) involved consideration of solvent desorption at the growing faces.

PMID- 10927430
TI  - Modulated structures of Cs2HgCl4: the 5a superstructure at 185 K and the 3c
      superstructure at 176 K.
AB  - Crystalline dicaesium mercury tetrachloride (Cs(2)HgCl(4)) is isomorphous with
      beta-K(2)SO(4) (space group Pnma, Z = 4) in its normal phase at room temperature.
      On cooling a sequence of incommensurate and commensurate superstructures occurs,
      below T = 221 K with modulations parallel to a*, and below 184 K with modulations
      along c*. The commensurately modulated structures at T = 185 K with q = (1/5)a*
      and at T = 176 K with q = (1/3)c* were determined using X-ray scattering with
      synchrotron radiation. The structure at T = 185 K has superspace group
      Pnma(alpha,0,0)0ss with alpha = 0.2. Lattice parameters were determined as a = 5
      x 9.7729 (1), b = 7.5276 (4) and c = 13.3727 (7) A. Structure refinements
      converged to R = 0.050 (R = 0.042 for 939 main reflections and R = 0.220 for 307
      satellites) for the section t = 0.05 of superspace. The fivefold supercell has
      space group Pn2(1)a. The structure at T = 176 K has superspace group
      Pnma(0,0,gamma)0s0 with gamma = 1/3. Lattice parameters were determined as a =
      9.789 (3), b = 7.541 (3) and c = 3 x 13.418 (4) A. Structure refinements
      converged to R = 0.067 (R = 0.048 for 2130 main reflections, and R = 0.135 for
      2382 satellite reflections) for the section t = 0. The threefold supercell has
      space group P112(1)/a. It is shown that the structures of both low-temperature
      phases can be characterized as different superstructures of the periodic room
      temperature structure. The superstructure of the 5a-modulated phase is analysed
      in terms of displacements of the Cs atoms, and rotations and distortions of
      HgCl(4) tetrahedral groups. In the 3c-modulated phase the distortions of the
      tetrahedra are relaxed, but they are replaced by translations of the tetrahedral
      groups in addition to rotations.

PMID- 10927431
TI  - Renormalization of the phase transition in lead phosphate, Pb3(PO4)2, by high
      pressure: lattice parameters and spontaneous strain.
AB  - The unit-cell parameters of lead phosphate, Pb(3)(PO(4))(2), have been measured
      by single-crystal X-ray diffraction in a diamond-anvil cell under hydrostatic
      conditions to a maximum pressure of 6 GPa. The compound undergoes an improper
      ferroelastic phase transition at 1.81 +/- 0.01 GPa at 298 +/- 1 K from a low
      pressure monoclinic phase (space group C2/c) to a high-pressure trigonal phase.
      The space group of the high-pressure phase is R3;m or R3m and the phase boundary
      is the same as that crossed at ca 450 K at room pressure. The evolution of the
      spontaneous strain components arising from the phase transition is linear with
      pressure, indicating an effective critical exponent for the phase transition of
      beta = 0.50 +/- 0.03. Thus, the application of pressure strongly renormalizes the
      effective critical exponent of the order parameter from the value of 0.236 found
      in high-temperature experiments.

PMID- 10927432
TI  - Charge distribution as a tool to investigate structural details: meaning and
      application to pyroxenes.
AB  - The charge distribution (CD) method, previously introduced as a development of
      the bond-valence (BV) approach, is applied for the first time to mineral
      structures, and specifically to pyroxenes. CD essentially involves the
      distribution of the Effective Coordination Number (ECoN) of a cation among all
      the neighboring anions. This distribution is then interpreted in terms of
      distribution of 'charges', where 'charge' represents the formal oxidation state.
      Differently from BV, the CD description depends upon the geometry of each
      coordination polyhedron, which is characterized through ECoN (a non-integer
      number). The contribution of each cation-oxygen bond to ECoN, labelled 'bond
      weight', corresponds to the bond strength in the BV method, but it is defined in
      terms of bond-length ratio in each polyhedron and not as a function of the cation
      oxygen pair. The ratio q/Q of the formal oxidation number to the computed charge
      can be interpreted as a measure of the correctness of the structure (cation
      ratio) and of the degree of over- or under-bonding (anion ratio). A similar
      interpretation is not possible for the analogous quantities obtained through the
      BV approach. The analysis in terms of CD of the pyroxene chains (from 101
      structures) shows different trends as a function of composition, temperature and
      pressure; in particular it shows a different behaviour of the two
      crystallographically independent chains of orthopyroxenes and of P2(1)/c
      clinopyroxenes.

PMID- 10927433
TI  - Electron density study of KNiF3 by the vacuum-camera-imaging plate method.
AB  - The electron density measurements of KNiF(3), nickel potassium trifluoride, by
      the vacuum-camera-imaging plate (VCIP) method and using a four-circle
      diffractometer with scintillation counter, are performed and compared. In the IP
      (imaging plate) case evacuation allowed the background around peaks to be reduced
      50 times, which significantly increased the accuracy of the data, especially for
      high-angle reflections. A new VIIPP program for visualizing and integration of IP
      data was designed to treat the data, in which the correction for oblique
      incidence was applied. The resulting electron density reproduces all the features
      of the accurate conventional measurement.

PMID- 10927434
TI  - Electron density and electrostatic potential of KNiF3: multipole, orbital and
      topological analyses of vacuum-camera-imaging plate and four-circle
      diffractometer data.
AB  - The electron density and electrostatic potential of KNiF(3), nickel potassium
      trifluoride, were studied using multipole and orbital model treatment of the
      precision X-ray diffraction data measured by vacuum-camera-imaging plate and four
      circle diffractometer methods. Different experimental methods lead to similar
      multipole and atomic displacement parameters and to qualitatively the same
      electron densities. Good agreement was also achieved for the Laplacians of the
      electron density and the electrostatic potentials. Some pitfalls of the vacuum
      camera-imaging plate method that could be improved are discussed.

PMID- 10927435
TI  - P1 or P1;? Or something else?
AB  - The October 1998 release of the Cambridge Structural Database (1992) contains
      structural details (unit-cell dimensions and atom coordinates) for nearly 1300
      distinct entries under space group P1 (No. 1); for 279 of these entries, the
      space-group designation is incorrect. The most common type of error, occurring
      for 157 entries with Z > 1, seems to have resulted from a simple misprint - the
      omission of the 'overline' in the symbol P{?bar 1} as it appears in the original
      publication; in these cases the reported coordinates, when applied to space group
      P{?bar 1} rather than P1, lead to reasonable intermolecular distances and to
      apparently reliable structures. In the remaining 123 cases the space group is
      incorrect for more fundamental reasons and the atom coordinates should be
      revised. In approximately one-third of the structures in which chiral molecules
      crystallize in P1 with Z = 2, the two molecules are related by an approximate
      center of inversion. In some cases this pseudocenter is surprisingly exact, with
      r.m.s. deviations from centrosymmetry as small as 0.1 A, and may result in the
      same sort of refinement difficulties that inevitably arise when truly
      centrosymmetric structures are mistakenly refined in space group P1. It appears
      as though, for typical molecular compounds, standard crystal-structure techniques
      may be unable to distinguish between P1 and P{?bar 1} if the r.m.s. deviation
      from centrosymmetry is less than approximately 0.1 A.

PMID- 10927436
TI  - Structure and thermal behavior of the new superprotonic conductor
      Cs2(HSO4)(H2PO4).
AB  - Ongoing studies of the CsHSO(4)-CsH(2)PO(4) system, aimed at developing novel
      proton conducting solids, resulted in the new compound Cs(2)(HSO(4))(H(2)PO(4))
      (dicesium hydrogensulfate dihydrogenphosphate). Single-crystal X-ray diffraction
      (performed at room temperature) revealed Cs(2)(HSO(4))(H(2)PO(4)) to crystallize
      in space group P2(1)/n with lattice parameters a = 7.856 (8), b = 7.732 (7), c =
      7.827 (7) A, and beta = 99.92 (4) degrees. The compound has a unit-cell volume of
      468.3 (8) A(3) and two formula units per cell, giving a calculated density of
      3.261 Mg m(-3). Six non-H atoms and two H atoms were located in the asymmetric
      unit, with SO(4) and PO(4) groups randomly arranged on the single tetrahedral
      anion site. Refinement using all observed reflections yielded weighted residuals
      of 0.0890 and 0.0399 based on F(2) and F values, respectively. Anisotropic
      temperature factors were employed for all six non-H atoms and fixed isotropic
      temperature factors for the two H atoms. The structure contains zigzag chains of
      hydrogen-bonded anion tetrahedra that extend in the [010] direction. Each
      tetrahedron is additionally linked to a tetrahedron in a neighboring chain to
      give a planar structure with hydrogen-bonded sheets lying parallel to (1;01).
      Thermal analysis of the superprotonic transition in Cs(2)(HSO(4))(H(2)PO(4))
      showed that the transformation to the high-temperature phase occurs by a two-step
      process. The first is a sharp transition at 334 K and the second a gradual
      transition from 342 to 378 K. The heat of transformation for the entire process (
      approximately 330-382 K) is 44 +/- 2 J g(-1). Thermal decomposition of
      Cs(2)(HSO(4))(H(2)PO(4)) takes place at much higher temperatures, with an onset
      of approximately 460 K.

PMID- 10927437
TI  - Preparation and characterization of tetrachlorocobaltates(II) of alpha,omega
      alkylenediammonium. Magnetic and thermal properties. Crystal structure of
AB  - Tetrachlorocobaltates(II) of diprotonated alpha,omega-diaminoalkanes with the
      formula [NH(3)(CH(2))(n)NH(3)]CoCl(4), where n = 5 (cadaverine; 1,5
      pentanediammonium tetrachlorocobaltate), 8 (1,8-octanediammonium
      tetrachlorocobaltate) and 10 (1,10-decanediammonium tetrachlorocobaltate), were
      prepared. The compounds were studied by mass spectrometry, FT-IR and visible
      spectroscopy, magnetic susceptibility techniques and thermal analysis. The
      compounds contain the tetrahedral tetrachlorocobaltate(II) ion and the
      corresponding diprotonated diamine (cadaverine, 1,8-octamethylenediamine and 1,10
      decamethylenediamine). The compound corresponding to cadaverine crystallizes in
      the monoclinic space group P2(1)/c, with lattice parameters a = 7.1633 (7), b =
      15.940 (3), c = 11.137 (2) A, beta = 98.44 (1) degrees and Z = 4. Its crystal
      structure contains slightly distorted tetrahedral CoCl(4)(2-) ions: the largest
      difference in Co-Cl bond lengths is 0.029 A and the largest difference in Cl-Co
      Cl angles is 7.76 degrees. The compound also contains diprotonated cadaverine
      ions. An extensive hydrogen-bonding network connects these ions. The slightly
      positive deviations of the magnetic susceptibility from the Curie-Weiss law are
      in agreement with the (4)A(2) ground state for the tetrachlorocobaltate anion.
      The compounds with eight and ten C atoms show phase transitions in the solid
      state and a greater complexity is observed in their differential scanning
      calorimetry curves. Unfortunately, no suitable single crystals of these could be
      obtained.

PMID- 10927438
TI  - Crystal structure of layered bis(ethylenediamine)nickel hexavanadate as a new
      representative of the V6O14 series.
AB  - A new [Ni(NH(2)CH(2)CH(2)NH(2))(2)](V(6)O(14)) compound has been synthesized
      hydrothermally and was found to crystallize in the monoclinic system. The single
      crystal X-ray data leads to a disordered structure, which can be decomposed into
      two ordered models with different stacking of the V(6)O(14) layers. The structure
      of the layer is the same in both models and represents a new member of the
      V(6)O(14) series. All known structures from this series are constructed from the
      same chain of square pyramids (SP), which share alternatively adjacent or
      opposite edges of their bases. The differences lie in the orientation of the SP
      chains which are joined together by sharing corners with tetrahedra to form the
      layers. Combinatorial analysis of the V(6)O(14) structures was conducted,
      yielding ten possible symmetry groups for the series of V(6)O(14) layers. The
      known structures belong only to the three simplest cases with the highest
      symmetry.

PMID- 10927439
TI  - Intramolecular and intermolecular geometry of thiophenes with oxygen-containing
      substituents.
AB  - The intramolecular and intermolecular geometries of six thiophenes carrying
      oxygen-containing substituents have been determined. Crystals of 2
      methoxythiophene and 3-methoxythiophene were grown in situ on a diffractometer
      from liquid samples. The 2-methoxy group introduces significant distortions to
      the thiophene nucleus and each molecule participates in four S.O contacts leading
      to an infinite bilayer. The extended structure of 3-methoxythiophene comprises
      zigzag chains of molecules linked by S.O contacts. Molecules of 2-acetyl-3
      methoxythiophene are arranged in pairs about inversion centres, with ring
      centroids 3.835 A apart. 5-Cyano-3-hydroxythiophene adopts the hydroxythiophene
      tautomeric form which allows conjugation between the S atom and the nitrile
      group: O-H.N hydrogen bonding leads to chains which are cross-linked by S.O
      contacts to give infinite two-dimensional layers. 5-(Methylthio)thiophen-3(2H)
      one exists exclusively as the thiophen-3(2H)-one form in the solid state,
      allowing maximum conjugative interaction of both the ring heteroatom and the
      substituent with the carbonyl group: each molecule is linked to two of its
      neighbours through pairwise C-H.O interactions, forming ribbons.
      Spiro[cyclohexane-1,2'-2',3'-dihydrothiophen]-3'-one crystallizes with four
      independent molecules in the asymmetric unit with only minor differences between
      these: the five- and six-membered rings in each molecule are approximately
      orthogonal and C-H.O hydrogen bonding generates chains. The last two structures
      differ from the others in that they lack a fully aromatic thiophene system.

PMID- 10927440
TI  - Structure and molecular modelling of protected dipeptide fragment (Boc-Phe-Leu
      OBzl) of enkephalin.
AB  - The conformational characteristics of a flexible totally protected C-terminal
      dipeptide fragment (Boc-Phe-Leu-OBzl) of enkephalin are studied using X-ray data,
      molecular modelling and data retrieved from the Cambridge Structural Database.
      The dipeptide crystallizes with seven conformers in the asymmetric unit.
      C(27)H(36)N(2)O(5), T = 133 K, monoclinic, P2(1), a = 13.706 (3), b = 22.800 (3),
      c = 30.674 (5) A, beta = 97.15 (3) degrees, V = 9511 (3) A(3), Z = 14, D(c) =
      1.145 Mg m(-3). Six of the seven molecules exhibit folded conformations with
      hydrophobic groups disposed at the opposite side of the peptide backbone. The
      characteristic Phi(1) and Psi(1) angles of the Phe residue and Phi(2) of the Leu
      fragment are in the allowed region defined in the Ramachandran diagram. However,
      they do not belong to the family of the lowest energy conformations. In the
      crystal, molecules are interconnected via N-H.O hydrogen bonds of peptide groups
      forming an infinite sheet similar to a parallel beta-sheet. Molecular dynamics
      simulations performed in vacuo reproduce the conformers and rotamers detected in
      the solid state.

PMID- 10927441
TI  - Self-assembly of NH-pyrazoles via intermolecular N-H.N hydrogen bonds.
AB  - The crystal structures of two NH-pyrazole derivatives forming intermolecular N
      H.N hydrogen bonds are reported: 5-methyl-4-(3-methylpyrazol-5-yl)pyrazol-3-ol,
      C(8)H(10)N(4)O (P1), and 3-methyl-5-dihydro-1H-naphtho[1,2-d]pyrazole
      hemihydrochloride, C(12)H(12)N(2).-C(12)H(13)N(2)(+).Cl(-) (P2). 26 other
      structures are surveyed in order to obtain a deeper insight into the ways NH
      pyrazoles self-assemble by means of intermolecular N-H.N hydrogen bonds in
      molecular crystals. A limited number of compounds form chains or dimers via
      homonuclear N(+)-H.N positive-charge-assisted hydrogen bonds, typical of proton
      sponges, which can be remarkably short [e.g. N.N 2.714 (3), N-H 1.09 (3), H.N
      1.63 (3) A, N-H.N 169 (3) degrees in (P2)]. Most pyrazoles, however, pack via
      neutral N-H.N bonds which are formally assisted by resonance (resonance-assisted
      hydrogen bond, RAHB) through the.N=C-C=C-NH. iminoenamine fragment, contained in
      the ring, giving rise to dimers, trimers, tetramers and infinite chains of
      pyrazole molecules. Surprisingly, the resonance does not appear to shorten the N
      H.N bond with respect to the accepted mean value N.N 2.97 (10) A for non-resonant
      N-H.N bonds. It is shown that this is due to the internal pi-delocalization of
      the pyrazole ring, which can be hardly increased by the hydrogen-bond
      interaction, except in symmetrically 3,5-substituted pyrazoles which display N.N
      distances as short as 2.82 A, identical C-C and C-N distances in the two halves
      of the pyrazole molecule, and typical phenomena of N-H.N dynamical proton
      disorder, detectable by (15)N-CP/MAS solid-state NMR.

PMID- 10927442
TI  - Interplay of hydrogen bonding and other molecular interactions in determining the
      crystal packing of a series of anti-beta-ketoarylhydrazones.
AB  - The crystal structures of six anti-beta-ketoarylhydrazones are reported: (a1) (E)
      2-(4-cyanophenylhydrazono)-3-oxobutanenitrile; (a2) (E)-2-(4
      methylphenylhydrazono)-3-oxobutanenitrile; (a3) (E)-2-(4-acetylphenylhydrazono)-3
      oxobutanenitrile; (a4) (E)-2-(2-methoxy-phenylhydrazono)-3-oxobutanenitrile; (a5)
      (E)-2-(2-acetylphenylhydrazono)-3-oxobutanenitrile; (a6) (E)-2-(2
      nitrophenylhydrazono)-3-oxobutanenitrile. All compounds contain the pi-conjugated
      heterodienic group HN-N=C-C=O and could form, at least in principle, chains of
      intermolecular N-H.O hydrogen bonds assisted by resonance (RAHB-inter). Compounds
      (a1) and (a2) form this kind of hydrogen bond though with rather long N.O
      distances of 2.948 (3) and 2.980 (2) A, and compound (a6) undergoes the same
      interaction but even more weakened [N.O 3.150 (1) A] by the intramolecular
      bifurcation of the hydrogen bond donated by the N-H group. The intrinsic weakness
      of the intermolecular RAHB makes possible the setting up of alternative packing
      arrangements that are controlled by an antiparallel dipole-dipole (DD)
      interaction between two C=O groups of the beta-ketohydrazone moiety [compounds
      (a4) and (a5)]. The critical factors that cause the switching between the
      different packings turn out to be the presence of hydrogen bonding accepting
      substituents on the phenyl and, most frequently, the intramolecular N-H.O bond
      with the O atom of the phenyl o-substituent. The crystal packing is widely
      determined by RAHB-inter (three cases) or DD (two cases) interactions. Only
      compound (a3) displays a different packing arrangement, where the DD interaction
      is complemented by a non-resonant hydro-gen bond between a p-acetyl phenyl
      substituent and the hydrazone N-H group [N.O 2.907 (2) A]. Crystal densities
      range from 1.24 to 1.44 Mg m(-3) and are shown to increase with the number of
      intermolecular hydrogen bonds and other non-van der Waals interactions.

PMID- 10927443
TI  - A comparative study of the crystal structures of tetrahalogenated hydroquinones
      and gamma-hydroquinone.
AB  - gamma-Hydroquinone (1) and its tetrafluoro, tetrachloro and tetrabromo
      derivatives (2), (3) and (4) adopt crystal structures that have an almost
      invariant system of O-H.O hydrogen bonds. However, within this O-H.O framework,
      the four structures display variations that are characteristic of the C-H, C-F, C
      Cl and C-Br groups. In the parent compound (1) aromatic rings are packed with a
      herringbone geometry, whilst in the halogenated derivatives (3) and (4),
      polarization-type halogen.halogen contacts are optimized. The fluoro derivative
      (2) is exceptional in that neither of the above possibilities is adopted, even
      though the O-H.O scaffolding does not per se prohibit either of them
      geometrically.

PMID- 10927445
TI  - Graph-set analysis of hydrogen-bond patterns: some mathematical concepts.
AB  - To provide a foundation for further theoretical and software development of the
      application of graph sets to patterns of hydrogen bonding and other
      intermolecular interactions a number of mathematical concepts and tools are
      defined, developed and demonstrated. Following a review of the basic definitions
      and uses of graph sets, the directional properties of hydrogen bonds are now
      included in the treatment. The concepts of a constructor graph and covalent
      distance matrix have been developed to aid in the generation of a qualitative
      descriptor for the straightforward, consistent and ultimately automatic (with
      appropriate software) definition of patterns. An additional mathematical tool,
      the arrowed T-labeling, has been developed to deal with situations in which
      pattern-forming moieties are located on crystallographic special positions. To
      demonstrate the utility and various features of these concepts they are applied
      in detail to two particular structures, polymorphic iminodiacetic acid [N
      (carboxymethyl)glycine] and trans-tetraamminedinitrocobalt(III) acetate. To
      facilitate the application and use of graph sets many of these developments have
      already been incorporated into the software of the Cambridge Structural Database,
      as described in the accompanying paper.

PMID- 10927444
TI  - Order-disorder phenomena determined by high-resolution powder diffraction: the
      structures of tetrakis(trimethylsilyl)methane C
AB  - The compounds tetrakis(trimethylsilyl)methane C[Si(CH(3))(3)](4) (TC) and
      tetrakis(trimethylsilyl)silane Si[Si(CH(3))(3)](4) (TSi) have crystal structures
      with the molecules in a cubic closed-packed (c.c.p.) stacking. At room
      temperature both structures have space group Fm{?bar 3}m (Z = 4) with a = 13.5218
      (1) A, V = 2472.3 (1) A(3) for TSi, and a = 12.8902 (2) A, V = 2141.8 (1) A(3)
      for TC. X-ray scattering data can be described by a molecule with approximately
      sixfold orientational disorder, ruling out a structure with free rotating
      molecules. Upon cooling, TSi exhibits a first-order phase transition at T(c) =
      225 K, as is characterized by a jump of the lattice parameter of Deltaa = 0.182 A
      and by an exothermal maximum in differential scanning calorimetry (DSC) with
      DeltaH = 11.7 kJ mol(-1) and DeltaS = 50.0 J mol(-1) K(-1). The structure of the
      low-temperature phase is refined against X-ray powder data measured at 200 K. It
      has space group P2(1)3 (Z = 4), a = 13.17158 (6) A and V = 2285.15 (2) A(3). The
      molecules are found to be ordered as a result of steric interactions between
      neighboring molecules, as is shown by analyzing distances between atoms and by
      calculations of the lattice energy in dependence on the orientations of the
      molecules. TC has a phase transition at T(c1) = 268 K, with Deltaa(1) = 0.065 A,
      DeltaH(1) = 3.63 kJ mol(-1) and DeltaS(1) = 13.0 J mol(-1) K(-1). A second first
      order phase transition occurs at T(c2) = 225 K, characterized by Deltaa(2) =
      0.073 A, DeltaH(2) = 6.9 kJ mol(-1) and DeltaS(2) = 30.0 J mol(-1) K(-1). The
      phase transition at higher temperature has not been reported previously. New NMR
      experiments show a small anomaly in the temperature dependence of the peak
      positions in NMR to occur at T(c2). Rietveld refinements were performed for the
      low-temperature phase measured at T = 150 K [space group P2(1)3, lattice
      parameter a = 12.609 (3) A], and for the intermediate phase measured at T = 260 K
      [space group Pa{?bar 3}, lattice parameter a = 12.7876 (1) A]. The low
      temperature phase of TC is formed isostructural to the low-temperature phase of
      TSi. In the intermediate phase the molecules exhibit a twofold orientational
      disorder.

PMID- 10927446
TI  - Visualization and characterization of non-covalent networks in molecular
      crystals: automated assignment of graph-set descriptors for asymmetric molecules.
AB  - A method of visualizing intermolecular networks (for example, hydrogen-bonded
      networks) in the crystalline state has been developed, based on the concept of
      link atoms, i.e. those atoms deemed to be in contact with each unique molecule or
      ion in the crystal chemical unit (CCU). Extension of a structure using each of
      these primary links can be achieved, enabling the generation and investigation of
      extended networks. Algorithms have been developed for the automatic assignment of
      graph-set notation for patterns up to second level, i.e. those involving one or
      two crystallographically independent non-covalent bonds, in the absence of
      internal crystallographic symmetry in the unique molecules of the CCU. The self,
      ring, chain and discrete motifs may be displayed by highlighting the atoms and
      bonds comprising the pattern. These methodologies have been implemented in the
      Cambridge Structural Database program PLUTO.

PMID- 10927447
TI  - TEMPO radicals showing magnetic interactions. II. 4-(Benzylideneamino)-TEMPO and
      related compounds.
AB  - X-ray crystal structure analyses were performed on 4-(Ar-methyleneamino)-TEMPO
      radicals at room temperature (TEMPO = 2,2,6,6-tetramethylpiperidyl-1-oxyl): Ar =
      Ph [4-(benzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl], 4-MeS-Ph [2,2,6,6
      tetramethyl-4-(4-methylthiobenzylideneamino)piperidyl-1-oxyl], 4-Me-Ph [4-(4
      methylbenzylideneamino)-2,2,6,6-tetramethylpiperidyl-1-oxyl], 4-PhO-Ph [2,2,6,6
      tetramethyl-4-(4-phenoxybenzylideneamino)piperidyl-1-oxyl], 4-MeSO(2)-Ph [2,2,6,6
      tetramethyl-4-(4-methylsulfonylbenzylideneamino)piperidyl-1-oxyl], 3-Py [2,2,6,6
      tetramethyl-4-(3-pyridylmethylideneamino)piperidyl-1-oxyl] and 2-Naph [2,2,6,6
      tetramethyl-4-(2-naphthylideneamino)piperidyl-1-oxyl]. Structures of Ph and 4-Me
      Ph derivatives were also determined at 100 K. Some of these crystals have been
      revealed to show intermolecular ferromagnetic interactions at an extremely low
      temperature. Structural features of crystals of Ph, 4-MeS-Ph and 3-Py
      derivatives, which show ferromagnetic interactions, are very similar to each
      other. In these crystals, O atoms are arranged to form a sheet. The ferromagnetic
      interactions are considered to be transferred through O.H van der Waals'
      interactions of the beta-H atoms of the neighboring TEMPO rings within the sheet.
      Between O.O sheets, the aryl groups are arranged in a herringbone manner. The
      crystal structure of the 4-Me-Ph derivative, which shows an antiferromagnetic
      interaction, is also pseudo-isostructural with those of Ph, 4-MeS-Ph and 3-Py
      derivatives, while the arrangement of the aryl groups is different. The packing
      mode of the crystals of the 4-MeSO(2)-Ph derivative, of which the Weiss constant
      straight theta is nearly zero, is very different from those of the other
      derivatives showing magnetic interactions. The fact that the crystal structure of
      the paramagnetic 4-MeSO(2)-Ph derivative does not show the O.O sheet structure
      accompanying the O.beta-H interactions indicates that the intermolecular
      ferromagnetic interactions through beta-H atoms within the O.O sheet are
      important for these TEMPO radical crystals.

PMID- 10927448
TI  - 2,4,6-Triisopropylbenzenesulfonamide: Monte Carlo structure solution from X-ray
      powder diffraction data for a molecular system containing four independent
      asymmetric rotors.
AB  - The crystal structure of 2,4,6-triisopropylbenzenesulfonamide, C(15)H(25)NO(2)S,
      has been solved from X-ray powder diffraction data collected at 120 (1) K using
      synchrotron radiation and refined by Rietveld methods. The structure was solved
      by the application of a Monte Carlo method in which trial structures were
      generated by random movement of the molecule in the unit cell and assessed using
      a full-profile-fitting technique. Intramolecular flexibility was introduced into
      the structure solution in the form of four independent asymmetric rotors,
      allowing the isopropyl and sulfonamide groups to rotate freely within the
      molecule. The structure is monoclinic P2(1)/c, a = 16.9600 (6), b = 8.1382 (2), c
      = 11.7810 (2) A, beta = 104.777 (2) degrees with Z = 4. The molecules are linked
      by N-H.O hydrogen bonds, with N.O distances of 2.77 (1) and 2.92 (1) A, into two
      dimensional sheets built from R(2)(2)(8) and R(6)(6)(20) rings.

PMID- 10927449
TI  - Local similarity in organic crystals and the non-uniqueness of X-ray powder
      patterns.
AB  - Two new concepts for molecular solids, 'local similarity' and 'boundary
      preserving isometry', are defined mathematically and a theorem which relates
      these concepts is formulated. 'Locally similar' solids possess an identical short
      range structure and a 'boundary-preserving isometry' is a new mathematical
      operation on a finite region of a solid that transforms mathematically a given
      solid to a locally similar one. It is shown further that the existence of such a
      'boundary-preserving isometry' in a given solid has infinitely many 'locally
      similar' solids as a consequence. Chemical implications, referring to the
      similarity of X-ray powder patterns and patent registration, are discussed as
      well. These theoretical concepts, which are first introduced in a schematic
      manner, are proved to exist in nature by the elucidation of the crystal structure
      of some diketopyrrolopyrrole (DPP) derivatives with surprisingly similar powder
      patterns. Although the available powder patterns were not indexable, the
      underlying crystals could be elucidated by using the new technique of ab initio
      prediction of possible polymorphs and a subsequent Rietveld refinement. Further
      ab initio packing calculations on other molecules reveal that 'local crystal
      similarity' is not restricted to DPP derivatives and should also be exhibited by
      other molecules such as quinacridones. The 'boundary-preserving isometry' is
      presented as a predictive tool for crystal engineering purposes and attempts to
      detect it in crystals of the Cambridge Structural Database (CSD) are reported.

PMID- 10927450
TI  - What is the best crystal size for collection of X-ray data? Refinement of the
      structure of glycyl-L-serine based on data from a very large crystal.
AB  - The dipeptide Gly-L-Ser was crystallized as part of a study on hydrogen-bonding
      patterns in the structures of dipeptides. Hydrogen-bond donors and acceptors have
      been assigned ranks (1 is best, 2 is next best etc.), and the observed hydrogen
      bond connectivity is compared with the hypothetical pattern in which the rank n
      donor associates with the rank n acceptor (n = 1, 2,.), and with the pattern
      observed in the retroanalogue L-Ser-Gly, which contains the same functional
      groups. Crystallization of the title compound produced very bulky crystals.
      Rather than reducing the size of one of these before data collection, three data
      sets with different exposure times were collected with a Siemens SMART CCD
      diffractometer on a very large specimen (2.2 x 2.0 x 0.8 mm). The crystal was
      subsequently shaped into a 0.30 mm-diameter sphere for collection of two
      additional data sets. The discussion of the refinement results focus on the
      effect of absorption correction for the various data sets, and a comparison of
      geometrical and thermal parameters. One advantage of using a large crystal, the
      great speed with which data can be obtained, has been exemplified by collection
      of a complete data set of good quality in less than 25 min.

PMID- 10927451
TI  - Volumetric measure of isostructurality.
AB  - The numerical descriptors of isostructurality are critically reviewed and to
      overcome their limitations a new volumetric measure is proposed. It is defined as
      the percentage ratio of the overlapping volume of molecules in the analyzed
      structures to the average of the corresponding molecular volumes. For the
      calculation of this index a numerical approach is presented, which is also
      capable of treating disordered structures. The use of isostructurality
      calculations is demonstrated using a series of examples. Homologous 9
      alkylthiophenanthrenes are used as simple illustrations of the necessity and
      applicability of the new descriptor. The structural changes in the inclusion
      compounds of 5-methoxysulfadiazine with chloroform, dioxane and tetrahydrofuran
      are analyzed and rationalized with the aid of isostructurality indices. The
      diverse relationships among a series of helical tubuland diols cocrystallized
      with simple phenols are also characterized. The modifications in molecular and
      crystal structures are correlated with the calculated degree of isostructurality.

PMID- 10927452
TI  - Structure refinement of Cu8GeS6 using X-ray diffraction data from a multiple
      twinned crystal. Erratum.
AB  - An error in the figures is reported. In the paper by Onoda et al. [Acta Cryst.
      (1999), B55, 721-725] the figures are given in the wrong order. Fig. 1 on p. 723
      should in fact be Fig. 2 on p. 724 and vice versa. The figure captions are given
      correctly.

PMID- 10927612
TI  - Atrial fibrillation: epidemiology, mechanisms, and management.

PMID- 10927613
TI  - Role of genetic factors in the pathogenesis of osteoporosis.
AB  - Osteoporosis is a common disease with a strong genetic component characterised by
      low bone mass, microarchitectural deterioration of bone tissue and an increased
      risk of fracture. Twin and family studies have shown that genetic factors play an
      important role in regulating bone mineral density and other determinants of
      osteoporotic fracture risk, such as ultrasound properties of bone, skeletal
      geometry and bone turnover. Osteoporosis is a polygenic disorder, determined by
      the effects of several genes, each with relatively modest effects on bone mass
      and other determinants of fracture risk. It is only on rare occasions that
      osteoporosis occurs as the result of mutations in a single gene. Linkage studies
      in man and experimental animals have defined multiple loci which regulate bone
      mass but the genes responsible for these effects remain to be defined. Population
      based studies and case-control studies have similarly identified polymorphisms in
      several candidate genes that have been associated with bone mass or osteoporotic
      fracture, including the vitamin D receptor, oestrogen receptor and collagen type
      IalphaI gene. The individual contribution of these genes to the pathogenesis of
      osteoporosis is small however, reflected by the fact that the relationship
      between individual candidate genes and osteoporosis has been inconsistent in
      different studies. An important aim of future work will be to define how the
      genes which regulate bone mass, bone turnover and other aspects of bone
      metabolism interact with each other and with environmental variables to cause
      osteoporosis in individual patients. If that aim can be achieved then there is
      every prospect that preventative therapy could be targeted to those at greatest
      risk of the osteoporosis, before fractures have occurred.

PMID- 10927614
TI  - IGF-I stimulation of luteinizing hormone secretion, IGF-binding proteins (IGFBPs)
      and expression of mRNAs for IGFs, IGF receptors and IGFBPs in the ovine pituitary
      gland.
AB  - Circulating concentrations of insulin-like growth factor-I (IGF-I) are reduced in
      juvenile sheep during nutritional growth restriction and the associated delay in
      puberty. Since exogenous IGF-I has been shown to stimulate luteinizing hormone
      (LH) secretion, it is postulated that endogenous IGF-I may act as a stimulatory
      metabolic signal to the pubertal ovine hypothalamo-pituitary axis, yet its site
      of action is unknown. Using coronal hypothalamic and pituitary sections from
      pubertal ewe lambs, in vitro autoradiography was used to localise 125I-labelled
      IGF-I binding, and gene expression for components of the IGF system was localised
      by in situ hybridisation using oligonucleotide probes. High concentrations of
      125I-IGF-I binding were seen in the pars tuberalis (PT) and pars distalis (PD) of
      the pituitary, and relatively little in the hypothalamus; binding in the PT but
      not the PD was displaced by excess unlabelled IGF-I. Large amounts of mRNA were
      detected for the type-1 receptor (IGF-1R) and for IGF-binding protein (IGFBP)-5,
      localised to the PT and PD, and less intense specific hybridisation signals were
      obtained with mRNAs for IGF-II, type-2 receptor (IGF-2R) and IGFBP-3. There was
      some evidence for specific hybridisation to IGFBP-4 mRNA in the PT. IGF-I, IGFBP
      1 and IGFBP-2 mRNAs were not detected in PT and PD. None of the genes were
      expressed in hypothalamic tissue. Western-ligand binding on PD extracts from male
      castrates revealed by their molecular weights the likely presence of IGFBPs-2, 
      3, and -5. Finally, cultured PD cells from abattoir-killed sheep were challenged
      with IGF-I (0.1, 1, 10 or 30 nM) or luteinizing hormone-releasing hormone (LHRH,
      10 nM) alone, or both together. Basal LH output was stimulated by 10 nM IGF-I
      (120+/-11.2%, P>0.05), 30 nM IGF-I (148+/-12.8%, P<0.01), and LHRH alone (200+/
      16.1%, P<0.001); there was no additive or subtractive effect of LHRH and IGF-I
      given together. Thus, an intrapituitary IGF system exists in sheep and the
      present results are consistent with an endocrine role for IGF-I in nutritional
      modulation of LH secretion at the level of the pituitary gland.

PMID- 10927615
TI  - Factors affecting production of luciferase and epitope-tagged IGF-I in porcine
      muscle after DNA injection.
AB  - Direct DNA injection into porcine skeletal muscle was investigated as an approach
      for studying roles of locally produced IGF-I on IGF-binding protein (IGFBP)
      production. To determine parameters for maximal reporter gene expression, and to
      investigate the effects of dose, time and weaning on exogenous DNA expression,
      plasmid DNA encoding firefly luciferase under control of a constitutive promoter
      and enhancer was injected in skeletal muscle of pigs. Results indicate that
      injected DNA does not migrate beyond 9 mm from injection sites and that 100
      microg DNA injections resulted in optimal luciferase activity. Maximum amounts of
      recombinant protein were observed 3 days after injection, and were reduced by
      weaning. Using these data, a second DNA injection study was performed using
      plasmid DNA containing a cDNA insert for epitope-tagged insulin-like growth
      factor-I (TIGF-I). Significant quantities of TIGF-I were detected by ELISA and
      confirmed by western blotting. Both IGFBP-2 and IGFBP-2 mRNA were increased in
      treated muscle compared with controls. We conclude that increased expression of
      IGF-I in muscle results in increased IGFBP-2. Furthermore, these data indicate
      that this in vivo approach of gene transfer results in biologically active
      recombinant protein production in porcine skeletal muscle, and provides an
      excellent in vivo model for studying the autocrine and (or) paracrine effects of
      locally produced growth factors in skeletal muscle.

PMID- 10927616
TI  - Primary cultured hepatocytes of the bony fish, Oreochromis mossambicus, the
      tilapia: a valid tool for physiological studies on IGF-I expression in liver.
AB  - In spite of the importance of IGF-I for growth and development, knowledge about
      regulation of its production in submammalian species is rather limited. In order
      to create a tool for investigation of direct regulatory effects on the expression
      of IGF-I in bony fish liver, a primary cell culture of hepatocytes from
      Oreochromis mossambicus, the tilapia, was established. The cells were viable for
      up to 3 days and IGF-I mRNA synthesis was detected by northern blot and
      semiquantitative reverse transcriptase (RT)-PCR. Northern blot analysis of the
      primary cultured hepatocytes revealed four different IGF-I transcripts, 0.5, 1.9,
      3.9 and 6.0 kb in size, which were identical to those in liver tissue. However,
      the expression rate was weaker than that in liver. The direct effects of
      recombinant tilapia (rt) growth hormone (GH) and salmon (s) IGF-I on the
      expression of IGF-I in primary cultured hepatocytes were investigated in time
      course and dose-response experiments. In untreated cultures, IGF-I mRNA decreased
      with time. Hepatocytes treated with 100 nM rtGH resulted in a pronounced
      stimulation of IGF-I mRNA expression throughout the experiment. Treatment with
      rtGH in concentrations ranging from 0.1 nM to 1 microM caused a clear dose
      dependent increase in the amount of IGF-I mRNA. Significant stimulation was
      obtained even with 0.1 nM, reaching a plateau with 10 nM. Neither significant
      inhibitory nor stimulatory effects were detected by adding sIGF-I from 0.1 nM to
      1 microM to the hepataocytes. Our results indicate that the established primary
      cell culture of tilapia hepatocytes is a useful system in which to study direct
      effects of potential regulators of bony fish liver cell function.

PMID- 10927617
TI  - Insulin activation of insulin receptor kinase in erythrocytes is not altered in
      non-insulin-dependent diabetes and not influenced by hyperglycemia.
AB  - Recent studies suggest that high glucose concentrations impair insulin receptor
      phosphorylation and kinase activation in certain cell models. To examine whether
      such an effect of glucose can also be demonstrated in vivo, insulin receptor
      kinase activation was studied in erythrocytes from 11 patients with non-insulin
      dependent diabetes (NIDDM), before and after reduction of hyperglycemia (from
      14.6+/-1.6 to 6.6+/-0.5 mmol/l fasting plasma glucose within 8.6+/-0.6 days). For
      the measurement of receptor kinase activation, cells were incubated with insulin
      (0-400 nmol/l), solubilized and insulin receptors immobilized to microwells
      coated with anti-insulin receptor antibody. Kinase activity towards insulin
      receptor substrate-1 and insulin binding were then measured in these wells.
      Kinase activities (expressed as amol phosphate transferred per min and per fmol
      insulin binding activity) were similar before (2.4+/-0.4 and 32.2+/-2.0 amol/min
      per fmol with 0 and 400 nmol/l insulin, respectively) and after improvement of
      metabolic control (2.4+/-0.5 and 32.0+/-2.3 amol/min per fmol with 0 and 400
      nmol/l insulin, respectively). Moreover, activities were also similar in 22
      hyperglycemic patients with NIDDM (2.1+/-0.3 and 35.1+/-1.4 amol/min per fmol
      with 0 and 400 nmol/l insulin, respectively) compared with those in 21 non
      diabetic control individuals (2.1+/-0.3 and 34.2+/-1.2 amol/min per fmol with 0
      and 400 nmol/l insulin, respectively). We conclude that insulin activation of
      erythrocyte insulin receptor kinase is not impaired in NIDDM and is not
      influenced by hyperglycemia.

PMID- 10927618
TI  - Role of 17beta-estradiol and/or progesterone on insulin sensitivity in the rat:
      implications during pregnancy.
AB  - The mechanism for the development of insulin resistance in normal pregnancy is
      complex and is associated with serum levels of both progesterone and 17beta
      estradiol. However, it remains unclear whether estrogens alone or progestins
      alone can cause insulin resistance, or whether it is a combination of both which
      produces this effect. We attempted to determine the role played by progesterone
      and/or 17beta-estradiol on the phenomena of sensitivity to insulin action that
      take place during pregnancy in the rat. Ovariectomized rats were treated with
      different doses of progesterone and/or 17beta-estradiol in order to simulate the
      plasma levels in normal pregnant rats. A euglycemic/hyperinsulinemic clamp was
      used to measure insulin sensitivity. At days 6 and 11, vehicle (V)- and
      progesterone (P)-treated groups were more insulin resistant than 17beta-estradiol
      (E)- and 17beta-estradiol+progesterone (EP)-treated groups. Nevertheless, at day
      16, the V, EP and E groups were more resistant to insulin action than the P
      group. On the other hand, the V, EP and E groups were more insulin resistant at
      day 16 than at day 6, whereas the P group was more insulin resistant at day 6
      than at day 16. Our results seem to suggest that the absence of female steroid
      hormones gives rise to a decreased insulin sensitivity. The rise in insulin
      sensitivity during early pregnancy, when the plasma concentrations of 17beta
      estradiol and progesterone are low, could be due to 17beta-estradiol. However,
      during late pregnancy when the plasma concentrations of 17beta-estradiol and
      progesterone are high, the role of 17beta-estradiol could be to antagonize the
      effect of progesterone, diminishing insulin sensitivity.

PMID- 10927619
TI  - Two estrogen receptors expressed in the teleost fish, Sparus aurata: cDNA
      cloning, characterization and tissue distribution.
AB  - Estrogen is an essential hormone for many reproductive and non-reproductive
      functions. The function of estrogen in the reproductive cycle of seabream (Sparus
      aurata), a protandrous hermaphrodite teleost fish, is complex but it is
      understood to be involved in sex inversion, a process that occurs in some
      individuals during the second reproductive season. Estrogen action is mediated by
      two estrogen receptor (ER) subtypes designated alpha and beta. As a step to
      understanding the mechanisms of estrogen action during natural and induced sex
      reversal in seabream, we have isolated two cDNAs encoding distinct forms of ER
      homologous to mammalian ERalpha and ERbeta. The seabream ERalpha clone
      (sbERalpha1), which was truncated in the A/B domain, corresponded to a variant
      differing in five amino acids from another recently cloned sbERalpha. The ERbeta
      clone (sbERbeta) encoded a protein 559 amino acids long and showed only 40%
      identity to sbERalpha. Northern blot analysis of liver and ovary mRNA indicated
      the presence of several transcripts of the two receptor subtypes. PCR analysis
      showed that the two receptors differed in their expression pattern. sbERalpha had
      a more restricted distribution, occurring mainly in testis, liver and heart, and
      sbERbeta was present in most tissues, being more abundant in ovary, testis,
      liver, intestine and kidney. The presence in seabream of two ERs with several ER
      transcripts and their pattern of distribution are consistent with the widespread
      effects of estrogen in different tissues.

PMID- 10927620
TI  - Adrenergic influences on coeliac ganglion affect the release of progesterone from
      cycling ovaries: characterisation of an in vitro system.
AB  - The superior ovarian nerve (SON) arrives at the ovary through the suspensory
      ligament and innervates mainly the ovarian stroma. Most neurones from which the
      SON fibres originate are located in the complex coeliac and mesenteric ganglia.
      Taking into account that other ganglia have been shown to have alpha- and beta
      adrenergic receptors, and that the coeliac ganglion receives adrenergic fibres
      from other sympathetic paravertebral and preaortic ganglia, we utilised
      adrenergic agonists and antagonists specific to the ganglion, to analyse the role
      of the alpha and beta receptors in ovarian physiology. To that end, it was
      necessary to develop and standardise an in vitro coeliac ganglion-SON-ovary
      (coeliac ganglion-SON-O) experimental system that would enable study of the
      release of steroids in the ovary in the absence of humoral factors. We
      investigated the effect of adrenergic agents on the liberation of progesterone in
      the different stages of the oestrous cycle. To this end we placed the coeliac
      ganglion and the ovary in different compartments, connected through the SON, to
      produce a system being studied as a whole. Combined neural and hormonal
      (luteinising hormone (LH)) effects were also examined. Non-specific stimulation
      with KCl in the ganglion compartment evoked different responses in terms of
      release of progesterone, depending on the physiological conditions of the cycle;
      this demonstrated the sensitivity and viability of the system. During pro
      oestrus, stimulation of the ganglion compartment with adrenergic agents such as
      the agonist noradrenaline or the beta-adrenergic antagonist propranolol, did not
      modify the release of progesterone. In contrast, the alpha-adrenergic antagonist,
      phentolamine, induced a strong inhibitory response. During the oestrous stage,
      noradrenaline was inactive, but phentolamine and propranolol exerted a strong
      stimulus throughout the experiment. On dioestrus day 1 (D1), both noradrenaline
      and propranolol increased the release of ovarian progesterone, whereas
      phentolamine had the opposite effect. Finally, on dioestrus day 2 (D2), what was
      noteworthy was the pronounced inhibitory effect of noradrenaline, whereas
      phentolamine was inactive and propranolol showed its greatest stimulatory effect.
      In order to compare the combined neural and endocrine effects on the ovarian
      release of progesterone, the experiment was carried out during stages D1 and D2,
      when the corpora lutea are at their peak of activity. Adrenergic agents were
      added to the ganglion and LH in a final concentration of 50 ng/ml was added to
      the ovarian comparment. Different effects were observed indicating a differential
      response to these agents in stimulated and basal conditions. We conclude that the
      in vitro coeliac ganglion-SON-ovary system is a functional entity because it
      possesses its own autonomic tone. This is verified because different basal values
      of progesterone appear in the different stages of the oestrous cycle. In similar
      fashion, variations of progesterone induced via the neural pathway were observed
      under different experimental conditions. In contrast, on D2, noradrenaline added
      to the ganglion compartment had an inhibitory effect on the liberation of ovarian
      progesterone. This would indicate that, during this phase, noradrenaline may not
      be the neurotransmitter released in the ovarian compartment, but that other
      inhibitory molecules might participate in the observed effects. Finally, during
      D2, the neural input would condition the ovarian response to LH, facilitating the
      decrease in progesterone necessary to start a new cycle. The experimental scheme
      is, in our opinion, a valuable tool for the study of peripheral neural
      participation in ovarian physiology.

PMID- 10927621
TI  - Developmental changes in the protein and mRNA content of a p115/transcytosis
      associated protein in the bovine mammary gland.
AB  - We measured the amounts of a vesicular transport factor, p115/transcytosis
      associated protein (p115/TAP) and its mRNA, in mammary glands from cows in which
      lactation was induced hormonally. The highest level of p115/TAP mRNA, determined
      by Northern blotting, was detected in the developing stage. In contrast to the
      mRNA level, the amount of protein, determined by immunoblot analysis using anti
      p115/TAP antibodies raised against a p115/TAP-derived recombinant fusion protein,
      was higher during the lactating stages than at other times. Immunohistochemical
      study showed that p115/TAP was predominantly localized in mammary epithelial
      cells. The p115/TAP was also detected in tissues other than the mammary gland
      but, in contrast to the situation in the mammary gland, the protein and its mRNA
      levels in those tissues were independent of the stage of lactation. The increased
      level of p115/TAP mRNA during the developing stage and the maintenance of
      p115/TAP protein during lactation suggest that the synthesis of p115/TAP is
      regulated during mammary development and differentiation, and also that the
      protein is involved in a function related to lactation.

PMID- 10927622
TI  - Stabilization of cyclin D1 mRNA via the phosphatidylinositol 3-kinase pathway in
      MCF-7 human breast cancer cells.
AB  - Treatment of quiescent MCF-7 human breast cancer cells with either the
      polypeptide growth factors insulin-like growth factor-I (IGF-I) or epidermal
      growth factor (EGF), the steroid hormone estradiol (E2) or the phorbol ester 12-O
      tetradecanoylphorbol-13-acetate (TPA) results in increased steady-state levels of
      cyclin D1 mRNA and protein. Unexpectedly, this elevation of cyclin D1 expression
      by all of these agents is inhibited by the specific phosphatidylinositol 3-kinase
      (PI3-K) inhibitor LY294002. Since transcriptional activation of the cyclin D1
      promoter by EGF, E2 and TPA is independent of PI3-K activity, these findings
      suggest a post-transcriptional role for PI3-K in the regulation of cyclin D1
      expression. Here we show that inhibition of PI3-K by LY294002 decreases the half
      life of the 4.5 kb cyclin D1 mRNA species. In contrast, the stability of the 1.5
      kb cyclin D1 mRNA is not affected by PI3-K inhibition. PI3-K-mediated
      stabilization of mRNA is not a general phenomenon, since other rapidly regulated
      and unstable mRNAs, such as those encoding c-fos, c-jun and c-myc, are not
      stabilized upon activation of the PI3-K signaling pathway.

PMID- 10927624
TI  - Gonadal suppression by a GnRH analogue does not alter somatic growth in rats with
      complete GH deficiency.
AB  - Sexual dimorphism of somatic growth in rats appears to reflect differing actions
      of sex steroids. However, mechanisms of gonadal steroid effects on the
      somatotropic axis are incompletely understood. To evaluate whether GH is involved
      in the effects of long-term gonadal suppression on somatic growth in rats, a GnRH
      agonistic analogue (GnRHa) was administered to normal Sprague-Dawley rats
      (controls) and to a strain of rats with complete growth hormone deficiency (GHD;
      n=4-6 in each group). Subcutaneous injection of GnRHa (2 mg/kg) or saline were
      given within 48 h after birth and repeated every 3 weeks. GnRHa treatment
      significantly reduced serum gonadal steroid levels in rats of both sexes with
      small testes in males and impaired development of internal genitalia in females.
      GnRHa-treated control females became significantly heavier (P<0.01 ANOVA for
      repeated measures) than saline-treated rats beginning at 8 weeks. However, female
      GHD rats with GnRHa treatment did not differ in body weight from rats receiving
      saline. In male rats, GnRHa treatment did not change body weight in either
      control or GHD rats. Serum IGF-I concentrations did not differ between treatment
      groups in GHD and control rats of either sex. Hepatic GH binding was reduced
      significantly by GnRHa treatment in female control rats (P<0.01), but not in
      female GHD rats. These data suggest that sexual dimorphism in body size and its
      modulation by estrogens are independent of circulating IGF-I levels suggesting
      non-endocrine IGF-I-mediated mechanisms, and that GH-induced somatic growth is
      modulated by estrogens, but not androgens, in rats.

PMID- 10927623
TI  - Temporal and hormonal regulation of inhibin protein and subunit mRNA expression
      by post-natal and immature rat ovaries.
AB  - The contribution of specific follicle populations to dimeric inhibin production
      and inhibin subunit mRNA expression by the rat ovary has been investigated in two
      model systems, granulosa cells isolated from 25-day-old diethylstilboestrol (DES)
      treated rats and post-natal rat ovaries, dispersed in culture or whole ovaries,
      using specific two-site immunoassays and 'real time' PCR. Media from FSH
      stimulated granulosa cell cultures fractionated by gel filtration and RP-high
      performance liquid chromatography revealed two predominant peaks of alpha subunit
      activity which were attributed to alpha subunit and 31 k dimeric inhibin-A. The
      corresponding inhibin-B levels were low. FSH stimulation did not alter the ratio
      of inhibin-A:alpha subunit produced by granulosa cells. All three inhibin subunit
      mRNAs were expressed by granulosa cells, with eight-fold more alpha subunit mRNA
      relative to either of the beta subunits. Administration of DES to immature rats
      prior to the isolation of granulosa cells from the ovary led to beta(A) and
      beta(B) mRNA expression being down-regulated in the absence of any significant
      change in alpha subunit expression by the granulosa cells. Inhibin-A, -B and 
      alpha subunit were produced by basal and stimulated cultures of ovarian cells
      prepared from 4-, 8- and 12-day-old rats, indicating that primary, preantral and
      antral follicles contribute to total inhibin production. Consistent with these
      results, follicles within these ovaries expressed all three inhibin subunit
      mRNAs, with maximal expression observed in the ovaries of 8-day-old rats. The
      appearance of antral follicles in the ovary at day 12 led to a decline in the
      mRNA levels of each of the subunits but was most evident for the beta subunits.
      There was a profound influence of secondary preantral follicles on dimeric
      inhibin-A production, with FSH stimulation increasing inhibin-A relative to alpha
      subunit levels in cultures of ovarian cells prepared from 8-day-old rats. Thus,
      preantral follicles exposed to FSH contribute significantly to beta(A) subunit
      production by the ovary. In contrast, primary and preantral follicles did not
      produce inhibin-B in response to FSH stimulation. Transforming growth factor-beta
      (TGF-beta) enhanced, in a time-dependent manner, the production of the inhibin
      forms by ovarian cells in culture, although inhibin-B production was not
      responsive until day 8. The simultaneous treatment of ovarian cell cultures with
      FSH and TGF-beta elicited the greatest increases in production of all the inhibin
      forms. In summary, ovaries of 4-, 8- and 12-day-old rats expressed inhibin
      subunit mRNAs and produced dimeric inhibin-A and -B and free alpha subunit.
      Preantral follicles (day-8 ovarian cell cultures) were particularly sensitive to
      stimulation by FSH and TGF-beta and had a substantial capacity for inhibin
      production. The production of oestrogen by follicles may be instrumental in
      regulating inhibin production given that beta subunit mRNA expression was down
      regulated by DES. The mechanisms by which inhibin-A and inhibin-B are
      individually regulated are likely to be similar during the post-natal period,
      when folliculogenesis is being established, and diverge thereafter, when inhibin
      A becomes the predominant form in the fully differentiated ovary.

PMID- 10927625
TI  - Hormonal regulation of glutathione S-transferase expression in co-cultured adult
      rat hepatocytes.
AB  - Glutathione S-transferases (GSTs) are subject to regulation by thyroid and sex
      hormones and by GH. We have used an in vitro experimental system comprising adult
      rat hepatocytes co-cultured with rat liver epithelial cells of primitive biliary
      origin, to distinguish between direct and indirect effects of various hormones on
      GSTs; to identify the GST subunits affected by individual hormones; and to
      investigate the level at which the hormones act. Tri-iodothyronine (T3),
      thyroxine (T4) and 17beta-oestradiol (OE2) reduced GST activities, whereas
      testosterone, dihydrotestosterone, and human growth hormone (hGH) had little
      effect on total GST activity. HPLC separation of the various GST subunits
      revealed that T3 and T4 reduced total GST content, in particular the abundance of
      subunits M1 and M2. The amount of the Pi-class subunit P1 was reduced by OE2.
      Treatment of the co-cultured cells with this hormone altered the GST subunit
      profile to one that is more similar to that observed in freshly isolated
      hepatocytes. Analysis of mRNAs demonstrated that some of the hormones act at a
      pre-translational level, whereas others act at a translational or post
      translational level to regulate the expression of various GST subunits.

PMID- 10927626
TI  - Interaction between substance P and TRH in the control of prolactin release.
AB  - Substance P (SP) may participate as a paracrine and/or autocrine factor in the
      regulation of anterior pituitary function. This project studied the effect of TRH
      on SP content and release from anterior pituitary and the role of SP in TRH
      induced prolactin release. TRH (10(-7) M), but not vasoactive intestinal
      polypeptide (VIP), increased immunoreactive-SP (ir-SP) content and release from
      male rat anterior pituitary in vitro. An anti-prolactin serum also increased ir
      SP release and content. In order to determine whether intrapituitary SP
      participates in TRH-induced prolactin release, anterior pituitaries were
      incubated with TRH (10(-7) M) and either WIN 62,577, a specific antagonist of the
      NK1 receptor, or a specific anti-SP serum. Both WIN 62,577 (10(-8) and 10(-7) M)
      and the anti-SP serum (1:250) blocked TRH-induced prolactin release. In order to
      study the interaction between TRH and SP on prolactin release, anterior
      pituitaries were incubated with either TRH (10(-7) M) or SP, or with both
      peptides. SP (10(-7) and 10(-6) M) by itself stimulated prolactin release. While
      10(-7) M SP did not modify the TRH effect, 10(-6) M SP reduced TRH-stimulated
      prolactin release. SP (10(-5) M) alone failed to stimulate prolactin release and
      markedly decreased TRH-induced prolactin release. The present study shows that
      TRH stimulates ir-SP release and increases ir-SP content in the anterior
      pituitary. Our data also suggest that SP may act as a modulator of TRH effect on
      prolactin secretion by a paracrine mechanism.

PMID- 10927627
TI  - Effects of infantile thymectomy on ovarian functions and gonadotrophin-induced
      ovulation in prepubertal mice: role of thymulin.
AB  - The effects of thymectomy performed on 10-day-old (Tx-10) mice on spontaneous
      puberty and the ovulatory response induced by gonadotrophin treatment were
      analysed, together with the effects of thymulin replacement from 10 days of age.
      Infantile thymectomy induced a delay of puberty, a decrease in serum 17beta
      oestradiol concentration and a reduced total number of follicles. Injection of
      thymulin (12 ng/g body weight) to Tx-10 mice resulted in an earlier onset of
      puberty, a decrease in the weights of ovaries and uterus, and an increase in
      serum 17beta-oestradiol concentrations. In control and Tx-10 mice, treatment with
      pregnant mare serum gonadotrophin (PMSG) (5 IU) at 25 days of age resulted in
      ovulation and the numbers of ova shed by ovulating animals were similar. When the
      animals were injected with 1 IU PMSG ovulation did not occur. In Tx-10 mice, both
      1 and 5 IU PMSG increased the number of follicles to values similar to those
      observed in the controls. In Tx-10 mice the sequential injection of PMSG (1 IU)
      and human chorionic gonadotrophin (hCG) (3 IU) resulted in ovulation, but the
      number of ova shed was lower than in controls. When these animals were injected
      daily with thymulin, an increase in the number of ova shed and serum 17beta
      oestradiol concentrations was observed. The uterine weight of Tx-10 mice was
      always significantly reduced in response to gonadotrophin treatment. Thymulin
      injection in PMSG-hCG-treated Tx-10 mice provoked a significant increase in
      uterine weight. The results suggest that the presence of the thymus after the
      neonatal period is necessary to normal ovarian development and function. The
      increase in gonadotrophin-induced ovarian response produced by thymulin
      replacement indicates that this peptide has a role in this process as one of the
      connecting signals between thymus and ovaries.

PMID- 10927628
TI  - Effect of adrenomedullin infusion on basal and stimulated aldosterone secretion
      in conscious sheep with cervical adrenal autotransplants.
AB  - In vivo and in vitro studies have shown conflicting effects of adrenomedullin
      (ADM) on the secretion of steroid hormones from the adrenal gland. While some
      investigators report no effect of this peptide on the output of various hormones,
      others have reported both stimulatory and inhibitory roles for ADM. We have shown
      that basal aldosterone secretion rate (ASR), in conscious sheep with cervical
      adrenal autotransplants, did not change when ADM was infused directly into the
      adrenal arterial supply. While not affecting basal ASR, ADM did produce
      pronounced increases in adrenal blood flow (BF). This elevation of BF in
      association with ADM infusion was seen in all subsequent experiments. When
      aldosterone output was acutely stimulated by angiotensin II (AngII), potassium
      chloride (KCl) and adrenocorticotrophic hormone (ACTH), ADM was seen to
      drastically reduce the secretion of aldosterone with all agonists studied. After
      pre-exposure to ADM, all three agonists increased ASR but the magnitude of the
      responses were somewhat blunted. ADM did not have the same effect on cortisol
      secretion stimulated by ACTH, suggesting that the ability of this peptide to
      influence adrenal gland function is limited to the zona glomerulosa. In
      conditions of chronic elevation of aldosterone levels, such as in Na deficiency,
      ADM did not display the same inhibitory abilities seen in the acute stimulation
      experiments. Hence, ADM has been shown to have a direct, inhibitory role on the
      acute stimulation of aldosterone by AngII, KCl and ACTH while not affecting basal
      or chronic aldosterone secretion or cortisol secretion stimulated by ACTH.

PMID- 10927629
TI  - Dehydroepiandrosterone prevents lipid peroxidation and cell growth inhibition
      induced by high glucose concentration in cultured rat mesangial cells.
AB  - The oxidative stress induced by high glucose concentration contributes to tissue
      damage associated with diabetes, including renal injury. Dehydroepiandrosterone
      (DHEA), the major secretory product of the human adrenal gland, has been shown to
      possess a multi-targeted antioxidant activity which is also effective against
      lipid peroxidation induced by high glucose. In this study we evaluated the effect
      of DHEA on the growth impairment which high glucose concentration induces in
      cultured rat mesangial cells. Primary cultures of rat mesangial cells were grown
      for 10 days in media containing either normal (i.e. 5.6 mmol/l) or high (i.e. 30
      mmol/l) concentrations of glucose, without or with DHEA at different
      concentrations. The impairment of cell growth induced by high glucose was
      reversed by 100 nmol/l and 500 nmol/l DHEA, which had no effect on mesangial
      cells cultured in media containing glucose at the normal physiological
      concentration (5.6 mmol/l). In high-glucose cultured mesangial cells, DHEA also
      attenuated the lipid peroxidation, as measured by thiobarbituric acid reactive
      substances (TBARS) generation and 4-hydroxynonenal (HNE) concentration, and
      preserved the cellular content of reduced glutathione as well as the membrane
      Na+/K+ ATPase activity. The data further support the protective effect of DHEA
      against oxidative damage induced by high glucose concentrations, and bring into
      focus its possible effectiveness in preventing chronic complications of diabetes.

PMID- 10927630
TI  - Novel cardiac peptide hormone in several teleosts.
AB  - To find out the significance of the newest member of the natriuretic peptide
      family, salmon cardiac peptide (sCP), we have determined the distribution of the
      peptide and its mRNA as well as the tissue and plasma molecular forms in several
      teleosts. Using probes based on the salmon sCP cDNA in Northern blot analysis we
      found mRNA homologous to that of sCP to be present in the heart of 15 fish
      species representing nine different genera. We developed a specific RIA for the
      salmon 29 amino acid peptide to be able to study the distribution of the peptide
      in the heart and plasma of different fish species. Despite the probable
      interspecies differences in the peptide sequence, large quantities of
      immunoreactive sCP were found in the atrium, ventricle and plasma of most of the
      fish species studied, suggesting that a cardiac hormone homologous to sCP has an
      endocrine function in a large variety of teleost species. The molecular form of
      the hormone secreted and stored in the tissue was determined by gel filtration
      high pressure liquid chromatography. In salmon, as in most of the other fish
      species studied, the predominant immunoreactive sCP in plasma corresponded to the
      low molecular weight form, with a size similar to that of the biologically active
      29 amino acid sCP (sCP-29), whereas the form stored in the heart corresponded to
      the high molecular weight pro-sCP-sized material. The form secreted by isolated
      perfused salmon ventricle, in the basal state as well as when mechanically
      loaded, was the sCP-29-sized peptide, thus ruling out the possibility that the
      conversion from high to low molecular weight material is caused by plasma
      proteases. In conclusion, sCP-like peptides are produced and secreted from the
      heart of a large number of different fish species. Their post-translational
      processing appears to be remarkably similar to that of mammalian atrial
      natriuretic peptide.

PMID- 10927631
TI  - Chronic melanocortin 4 receptor blockage causes obesity without influencing
      sexual behavior in male rats.
AB  - We investigated the effects of continuous intracerebroventricular infusion of a
      melanocortin 4 receptor antagonist HS014 (cyclic [AcCys11, D-Nal14, Cys18, Asp
      NH2(22)]beta-MSH-(11-22)) over 12 days and a subsequent 12-day recovery period on
      food intake, body weight and copulatory behavior in male rats. The results show
      that the food intake increased immediately after the start of the infusion of
      HS014 (0.16 nmol/h) and progressively increased thereafter. No tachyphylaxis was
      observed. When the infusion of HS014 was terminated, the food-intake levels
      dropped. The body weights of the rats had increased by 17% by the end of the
      study, compared with controls. During the recovery period, the body weight
      decreased towards the levels of the control rats. These results indicate that
      overeating and the subsequent increases in body weight caused by blockage of the
      melanocortin 4 (MC4) receptor are reversible when the blockage is ended. We also
      tested the copulatory behavior of vigorous male rats in the presence of female
      rats in estrous. We registered mount latency, the number of mounts, the
      intromission latency, the number of intromissions, the ejaculation latency and
      the post-ejaculatory interval three times during the study and also after acute
      administration of HS014 and alpha-MSH. The sexual behavior of the male rats was
      not affected. These results indicate that the MC receptors, in particular the MC4
      receptor, may not be a major mediator of effects on copulatory behavior in male
      rats.

PMID- 10927632
TI  - alpha-MSH acetylation in the pituitary gland of the sea bream (Sparus aurata L.)
      in response to different backgrounds, confinement and air exposure.
AB  - MSH is a pituitary hormone derived by post-translational processing from POMC and
      involved in stress and background adaptation. N-terminal acetylation of MSH to
      monoacetyl alpha-MSH or diacetyl alpha-MSH increases the bioactivity of the
      peptide. The aim of this study was to characterize alpha-MSH acetylation in the
      sea bream (Sparus aurata L.) pituitary gland in response to the stressors air
      exposure and confinement, as well as in fish adapted for 15 days to a white, gray
      or black background. Pituitary homogenates were purified by reversed-phase HPLC
      (RP-HPLC). The alpha-MSH content of fractions was measured by RIA. Immunoreactive
      RP-HPLC fractions were further analyzed by electrospray mass spectrometry and the
      peptide sequence determined as SYSMEHFRWGKPV-NH2. In the pituitary gland of sea
      bream, des-, mono- and diacetyl alpha-MSH were identified. Then plasma alpha-MSH
      levels were measured in sea bream adapted to different backgrounds. Surprisingly,
      we found the highest plasma alpha-MSH levels in white-adapted as compared with
      black-adapted sea bream with intermediate values for gray-adapted fish. This
      observation is in contrast with results that have been obtained in eel, trout or
      terrestrial vertebrates. Next, des-, mono- and diacetyl alpha-MSH forms were
      measured in homogenates of the pituitary gland and in plasma of sea bream exposed
      to air, to confinement, or to different backgrounds. Monoacetyl alpha-MSH was the
      predominant form in all control and experimental groups. The lowest content of
      monoacetyl alpha-MSH relative to des- and diacetyl alpha-MSH was found in white
      adapted fish. Levels of des- and diacetyl alpha-MSH forms were similar under all
      conditions. We observed that monoacetyl alpha-MSH is the most abundant isoform in
      the pituitary gland after background adaptation, confinement and air exposure, in
      sea bream. These data indicate that the physiologically most potent isoform of
      alpha-MSH may vary from species to species.

PMID- 10927633
TI  - Processing and release of human proinsulin-cleavage products into culture media
      by different engineered non-endocrine cells: a specific assessment by capillary
      electrophoresis.
AB  - The aim of this study was to compare the metabolic pathway to mature insulin
      through the intermediate forms (32-33 split, 65-66 split, des31,32 and des64,65)
      in human or murine cells engineered for the release of wild-type human proinsulin
      and in a genetically mutated one, in the search for a new approach for an insulin
      dependent diabetes mellitus cure by gene therapy. Primary human fibroblasts,
      myoblasts and stabilized cell lines (HepG2 and NIH3T3) were transduced either
      with a retroviral vector coding for wild-type proinsulin or for a genetically
      mutated one, carrying cleavage sites sensitive to furin. The pattern of all the
      proinsulin cleavage products released into the cell culture supernatants was
      analyzed by capillary electrophoresis. All the cells transduced with the wild
      type gene released intact proinsulin. HepG2 released a considerable amount of 65
      66 split and des64,65, while primary myoblasts released all the intermediate
      forms and a limited amount of mature insulin. All the cells transduced with a
      furin-sensitive proinsulin gene released a higher amount of mature insulin (23
      59% conversion yield) than the cells expressing wild-type proinsulin, whereas the
      total insulin was nearly constant. Only primary cells released all the cleavage
      products. Screening a wide variety of non-endocrine cells has revealed a large
      difference in the processing and release of immature and mature insulin forms,
      pointing to human hepatic cells as the most efficacious. Capillary
      electrophoresis provided on-line and in a single run a complete overview of the
      proinsulin metabolic pathway in different cells.

PMID- 10927634
TI  - Expression and regulation of connexin43 in rat Leydig cells.
AB  - Gap junctions are intercellular protein channels which provide a pathway for the
      exchange of ions and small molecules. This exchange of materials allows metabolic
      coupling of cells. Gap junction channels are made up of connexins, integral
      membrane proteins encoded by a multigene family. Rat testes contain mRNAs for at
      least five different connexins: Cx26, Cx32, Cx33, Cx37 and Cx43.
      Immunocytochemical studies have shown that Cx43 assembles gap junctions between
      Leydig cells. The present study investigated the expression and regulation of the
      Cx43 gene in rat Leydig cells. Purified Leydig cells were obtained from 40- to 80
      day-old Sprague-Dawley rats using a combination of arterial perfusion,
      collagenase digestion, centrifugal elutriation and Percoll gradient
      centrifugation. Leydig cells from 20- and 30-day-old rats were isolated without
      arterial perfusion or centrifugal elutriation. Cx43 mRNA was present in 20-day
      old rat Leydig cells, reached a plateau at day 40, and remained at high levels in
      65- and 80-day-old rat Leydig cells. To evaluate the regulation of Cx43 gene
      expression, Leydig cells were cultured overnight and then treated with human
      chorionic gonadotropin (hCG) for variable periods of time. Addition of hCG (10
      ng/ml) increased cytochrome P450 side-chain cleavage and steroidogenic acute
      regulatory protein mRNA levels and testosterone formation. However, Cx43 mRNA
      levels were inhibited by hCG in a time- and dose-dependent manner. Cx43 mRNA
      levels decreased 27% as early as 2 h after the addition of hCG and decreased 60%
      by 24 h. Treatment of Leydig cells with 8-bromo-cAMP (0.1 mM) for 6 and 24 h also
      reduced Cx43 mRNA levels by 36 and 56% respectively. Primary cultured Leydig
      cells stained strongly positive with anti-Cx43 monoclonal antibody. Treatment
      with hCG for 24 h reduced Cx43 signals and caused Cx43 to redistribute to the
      periphery of the cells. To evaluate the regulation of Cx43 in vivo, rats were
      treated with hCG (300 ng i.p.) and testes were removed 24 h later. Frozen section
      of testes revealed that these interstitial cells stained positive for 3beta
      hydroxysteroid dehydrogenase (3beta-HSD) by histochemical staining and were
      positive for Cx43 by immunofluorescence staining. The adjacent seminiferous
      tubules stained only weakly positive for Cx43. Twenty-four hours after hCG
      treatment, 3beta-HSD activity increased while Cx43 immunostaining of Leydig cells
      was reduced. In conclusion, gap junction channels of Leydig cells are regulated
      by hCG both in vivo and in vitro. hCG increased Leydig cell steroidogenesis and
      steroidogenic enzyme mRNA levels but caused a redistribution of Cx43.

PMID- 10927635
TI  - Exclusive androgenic effect of dehydroepiandrosterone in sebaceous glands of rat
      skin.
AB  - In order to analyze the hormonal effects of dehydroepiandrosterone (DHEA) in skin
      sebaceous glands, the precursor steroid was administered to ovariectomized (OVX)
      female Sprague-Dawley rats at a dose of 30 mg applied on the dorsal skin, twice
      daily, for 3, 6 and 12 months. In a parallel experiment, female OVX rats were
      treated with DHEA at the same daily percutaneous dose of 30 mg, alone or in
      combination with the antiandrogen Flutamide or the pure antiestrogen EM-800, for
      12 months, in order to determine the androgenic and/or estrogenic components of
      DHEA action. Treatment of female OVX rats with DHEA resulted in a similar mild to
      moderate hyperplasia of the sebaceous glands of both dorsal (site of application)
      and ventral skin, as illustrated by an increase in the number and size of the
      acini. The above-indicated effects were observed at all time intervals studied,
      beginning at 3 months of treatment, and they were not further increased after
      longer term administration of DHEA (for 6 and 12 months). The addition of
      Flutamide to DHEA treatment completely prevented the DHEA-induced changes in the
      sebaceous glands, whereas the antiestrogen EM-800 had no effect. The present data
      indicate an exclusive androgenic stimulatory action of DHEA on the sebaceous
      glands, thus pointing out the importance of local intracrine DHEA transformation
      into androgens for skin anatomical integrity and function, while showing that
      estrogens, if active in rat skin, do not originate from DHEA.

PMID- 10927636
TI  - Lanosterol 14alpha-demethylase (CYP51), NADPH-cytochrome P450 reductase and
      squalene synthase in spermatogenesis: late spermatids of the rat express proteins
      needed to synthesize follicular fluid meiosis activating sterol.
AB  - Lanosterol 14alpha-demethylase (CYP51) is a cytochrome P450 enzyme involved
      primarily in cholesterol biosynthesis. CYP51 in the presence of NADPH-cytochrome
      P450 reductase converts lanosterol to follicular fluid meiosis activating sterol
      (FF-MAS), an intermediate of cholesterol biosynthesis which accumulates in gonads
      and has an additional function as oocyte meiosis-activating substance. This work
      shows for the first time that cholesterogenic enzymes are highly expressed only
      in distinct stages of spermatogenesis. CYP51, NADPH-P450 reductase (the electron
      transferring enzyme needed for CYP51 activity) and squalene synthase (an enzyme
      preceding CYP51 in the pathway) proteins have been studied. CYP51 was detected in
      step 3-19 spermatids, with large amounts in the cytoplasm/residual bodies of step
      19 spermatids, where P450 reductase was also observed. Squalene synthase was
      immunodetected in step 2-15 spermatids of the rat, indicating that squalene
      synthase and CYP51 proteins are not equally expressed in same stages of
      spermatogenesis. Discordant expression of cholesterogenic genes may be a more
      general mechanism leading to transient accumulation of pathway intermediates in
      spermatogenesis. This study provides the first evidence that step 19 spermatids
      and residual bodies of the rat testis have the capacity to produce MAS sterols in
      situ.

PMID- 10927637
TI  - Increased magnitude of relaxation to oestrogen in aorta from oestrogen receptor
      beta knock-out mice.
AB  - Micromolar concentrations of the biologically active oestrogen 17beta-oestradiol
      reduce agonist-induced force in vascular preparations through an unidentified
      mechanism. The aim of the present study was to investigate the importance of
      oestrogen receptor beta (ERbeta) for oestrogen-induced vascular relaxation.
      17beta-oestradiol was added to aortic rings from ERbeta knock-out (-/-) and wild
      type (+/+) mice precontracted with noradrenaline. 17beta-oestradiol caused a
      concentration-dependent (1-100 microM) relaxation of aortic rings from both -/-
      and +/+ animals of both sexes. Rings from male and female -/- mice were more
      sensitive to 17beta-oestradiol than those from +/+ mice. Medial thickness,
      determined by computerized image analysis, was similar in rings from -/- and +/+
      animals. Endothelium, as determined by immuno-cytochemistry, was present in -/-
      and +/+ aorta. Maximal noradrenaline evoked force and sensitivity to
      noradrenaline were similar in both groups. In summary ERbeta modulates vascular
      relaxation to microM concentrations of oestrogen; lack of ERbeta renders the
      vascular wall supersensitive to 17beta-oestradiol. Lack of ERbeta caused no
      change in vascular wall morphology suggesting that this ER subtype is not
      involved in vascular structure development.

PMID- 10927638
TI  - Picking up the pace of your daily walk.

PMID- 10927639
TI  - Chest pain in women - in the head or in the heart?

PMID- 10927640
TI  - Can walnuts prevent heart disease?

PMID- 10927641
TI  - Have the problems of beta blockers been overrated?

PMID- 10927642
TI  - Ask the doctor. I am 78 years old and have diabetes and a heart murmur from
      narrowing of my aortic valve. My doctor tells me that the narrowing is not so
      severe that I need surgery, but warns me that I may need an operation some day.
      Naturally, I would like to avoid that possibility. Is there anything I can do to
      reduce the risk?

PMID- 10927643
TI  - Ask the doctor. The right ventricle bundle of nerves in my heart is blocked, and
      the doctor I went to did not seem concerned at all. Yet a friend of mine who had
      the same condition almost died when the left bundle shut down. He just happened
      to be in the hospital for another condition when it occurred, and they put a
      pacemaker in. He had some chest pain, but is otherwise OK. Do I need a pacemaker,
      too?

PMID- 10927644
TI  - Genetics. We've read the book, now what does it mean?

PMID- 10927646
TI  - Fatigue. Getting your energy back.

PMID- 10927645
TI  - Nutrition. Can taking vitamins protect your brain?

PMID- 10927647
TI  - Recreation. Keeping safe around the water.

PMID- 10927648
TI  - Pain. MSM: does it work?

PMID- 10927649
TI  - By the way, doctor... I'm 68, and I've been taking Viagra for about a year now.
      The drug is working for me, but I'm always a little scared that I am going to
      give myself a heart attack. Should I be?

PMID- 10927650
TI  - Attention deficient disorder -- part I.

PMID- 10927651
TI  - Cognitive rehabilitation of schizophrenia.

PMID- 10927652
TI  - Placebos and suicide.

PMID- 10927653
TI  - Diagnostic deficiencies.

PMID- 10927654
TI  - What is transcranial magnetic stimulation?

PMID- 10927655
TI  - Strength training.

PMID- 10927656
TI  - Four herbs.

PMID- 10927657
TI  - Treating hypertension: necessary but not sufficient.

PMID- 10927658
TI  - On call. I am 58 years old. I've always been healthy, but my doctor found that my
      cholesterol was 279. He prescribed Mevacor, and my cholesterol came down to 210.
      Do I still need to be on a low-fat diet?

PMID- 10927659
TI  - Obesity: portions out of proportion.

PMID- 10927660
TI  - Stretching for a better golf game.

PMID- 10927661
TI  - Panic: worry in the extreme.

PMID- 10927662
TI  - Hypnosis: en-tranced in the procedure room.

PMID- 10927663
TI  - Treating hot flashes with drugs.

PMID- 10927664
TI  - By the way, doctor. My doctor prescribed Fosamax to me for osteoporosis
      prevention, but it upsets my stomach. Are there any other proven medications for
      osteoporosis prevention?

PMID- 10927665
TI  - The indigenous fisherman divers of Thailand: diving-related mortality and
      morbidity.
AB  - The Urak Lawoi are indigenous fishermen on Thailand's west coast. The population
      includes an estimated 400 divers who dive using surface-supplied compressed air.
      In a cross-sectional survey conducted among the 6 major communities of Urak
      Lawoi, questionnaire-based interviews were administered to active divers, ex
      divers, and families or colleagues of divers who had died in the previous 5
      years. Six deaths resulting from diving-related accidents were identified,
      indicating a diving-related mortality rate of approximately 300 per 100,000
      person-years, while in the same 5-year period 11 divers had been disabled owing
      to diving-related events, indicating a diving-related disabling event rate of
      approximately 550 per 100,000 person-years. Among 342 active divers interviewed,
      one third reported having suffered from decompression illness, although based on
      reported current symptoms over 50% were classified as suffering from recurring
      non-disabling decompression illness. Physical examination conducted on a subset
      of 98 active divers revealed the presence of spinal injury (clonus, raised muscle
      tone, and heightened reflexes) and of joint damage (pain in one or more joint,
      crepitus, or restricted movement) in 24 and 30% respectively. Improved primary
      prevention and medical treatment are needed to reduce mortality and morbidity
      among this population.

PMID- 10927666
TI  - Deposition and retention of ultrafine aerosol particles in the human respiratory
      system. Normal and pathological cases.
AB  - The particle number concentration in ambient air is dominated by nanometer-sized
      particles. Recent epidemiological studies report an association between the
      presence of nanoparticles in inhaled air at the workplace and acute morbidity and
      even mortality in the elderly. A theoretical model of deposition of 20 nm
      particles in the human alveolus was formulated. Gas flow structure and deposition
      rate were calculated for alveoli with different elastic properties of lung
      tissue. Data obtained in the paper show increased convective effects and
      diffusional rate of deposition of nanoparticles for alveoli with higher stiffness
      of the alveolar wall. The retention of deposited particles is also higher in
      these pathological alveoli. Results of our calculations indicate a possibility of
      existence of a positive loop of coupling in deposition and retention of
      nanoparticles in the lung with pathological changes.

PMID- 10927667
TI  - Manual handling injuries in health care workers.
AB  - Nursing aides are particularly susceptible to manual handling injuries because
      they have the primary responsibility for heavy lifting. The aim of this study was
      to determine why a specific group of nursing aides have the highest manual
      handling injury rate in their hospital. The study investigated the adequacy of
      the manual handling training program, knowledge of manual handling, mechanical
      aid availability, and use of mechanical aids. Results indicated that the nursing
      aides' manual handling knowledge was adequate but that they rarely used
      mechanical aids. This lack of use of aids was in part due to an over-reliance on
      their own strength and abilities. This may have been due to a lack of suitable
      mechanical aids on the wards or a lack of familiarity with the available aids.
      This study suggests that neither training alone nor the purchase of equipment
      alone is likely to resolve manual handling problems.

PMID- 10927668
TI  - A model to analyze ergonomics working conditions.
AB  - An ergonomics and safety model to assess and evaluate the most critical
      industrial improvement areas in a developing nation. This study was initiated and
      supported by a Fortune 500 Corporation interested in improving its global
      operations in developing nations. This initiative was also fully supported by an
      emerging nation that was concerned with its ergonomics and safety problems. The
      model was tested and validated in the emerging nation and the results were used
      to further enhance the model so that it can be implemented and adapted to other
      similar work environments. The model provides a practical methodology that
      analyzes and evaluates an emerging nation's current work environments, suggests
      practical solutions, and recommends effective remedies.

PMID- 10927669
TI  - The effects of a change in work organization upon the work environment and
      musculoskeletal symptoms among letter carriers.
AB  - An organizational change among 82 postal workers was studied with the aim of
      evaluating the effects on the work environment, work ability, and musculoskeletal
      complaints. The study was undertaken in 2 suburbs of Stockholm, Sweden.
      Psychological work demands were estimated to be reduced at the 1-year follow-up
      but physical work demands had changed very little. In an observation study in a
      subgroup of older workers, the risk of overexertion at work and musculoskeletal
      complaints was reduced. In spite of that, most of the older participants (>/=35
      years) had unchanged or increased musculoskeletal symptoms. This shows the need
      for early preventive measures.

PMID- 10927670
TI  - The moderating role of hardiness and social support in the relation between job
      stressors and well-being. A lesson from a clerical women sample.
AB  - The study concerns the moderating role of two variables--hardiness and social
      support--in the relation between job stressors and well-being. It was checked if
      there is a connection between hardiness and social support, and if these
      variables are directly related to the level of well-being. It was also
      hypothesized that hardiness and social support buffer the negative influence of
      stressors on well-being. The fact that social support and well-being are
      multidimensional variables was taken into account. The cross-sectional study was
      conducted on a group of 200 women employed as office workers. The results showed
      that hardiness correlates with the indexes of emotional support as well as
      practical support coming from supervisors. The connection, however, was not
      strong. Hardiness and social support were directly connected with the level of
      well-being. Interaction of these two independent variables played a marginal
      role. As far as the buffering role of these variables was concerned, the results
      have shown that hardiness did not play a buffering role and social support did to
      a limited degree only. The results of the study proved that it is justifiable to
      treat social support and well-being as multidimensional variables.

PMID- 10927671
TI  - Occupational accidents of Finnish- and Swedish-speaking workers in Finland: a
      mental model view.
AB  - This article is based on 2 studies. The aim of the first study was to examine the
      differences in occupational accident frequency between the 2 main language groups
      in Finland. Based on 3 independent statistical data sets, it was shown that
      Swedish-speaking workers had about 40% fewer occupational accidents than Finnish
      speaking workers. The aim of the second study was to confirm the difference at
      company level. A field study in the province of Vaasa with 14 small and medium
      sized manufacturing companies revealed that the accident frequency of Swedish
      speaking workers was 21% lower than that of Finnish-speaking workers.

PMID- 10927672
TI  - Evaluation of dermal-epidermal skin equivalents ('composite-skin') of human
      keratinocytes in a collagen-glycosaminoglycan matrix(Integra artificial skin).
AB  - Integra artificial skin (Integra LifeSciences Corp., Plainsboro, NJ, USA) is a
      dermal template consisting of bovine collagen, chondroitin-6-sulphate and a
      silastic membrane manufactured as Integra. This product has gained widespread use
      in the clinical treatment of third degree burn wounds and full thickness skin
      defects of different aetiologies. The product was designed to significantly
      reduce the time needed to achieve final wound closure in the treatment of major
      burn wounds, to optimise the sparse autologous donor skin resources and to
      improve the durable mechanical quality of the skin substitute. The clinical
      procedure requires two stages. The first step creates a self neodermis, the
      second creates a self epidermis on the neodermis. However, it is desirable to
      cover major burn wounds early in a single step by a skin substitute consisting of
      a dermal equivalent seeded in vitro with autologous keratinocytes ('composite
      skin') out of which a full thickness skin develops in vivo.The goal of this
      experimental study was to develop a method to integrate human keratinocytes in
      homogeneous distribution and depth into Integra Artificial Skin. The seeded cell
      matrix composites were grafted onto athymic mice in order to evaluate their
      potential to reconstitute a human epidermis in vivo. We were able to demonstrate
      that the inoculated human keratinocytes reproducibly displayed a homogeneous
      pattern of distribution, adherence, proliferation and confluence. The cell-matrix
      composites grafted in this model exhibited good wound adherence, complete
      healing, minor wound contraction and had the potential to reconstitute an
      elastic, functional and durable human skin. Histologically we were able to show
      that the inoculated human keratinocytes in vivo colonised the matrix in a
      histomorphologically characteristic epidermal pattern (keratomorula, keratinocyte
      bubbling) and developed a persisting, stratified, keratinising epidermis which
      immunohistologically proved to be of human origin. These experimental results
      demonstrate the establishment of an effective cell cultivation process which may
      be suitable for scale-up production of the epidermal component as large-scale
      composite-skin grafts. When seeded into Integratrade mark and grafted onto the
      nude mouse a replacement skin with normal functioning dermal-epidermal components
      was developed. These results encourage the design of a clinical trial to assess
      the function of this composite graft in man.

PMID- 10927673
TI  - An anatomical structure which results in puffiness of the upper eyelid and a
      narrow palpebral fissure in the Mongoloid eye.
AB  - The typical Mongoloid eye differs from the Occidental one in puffiness of the
      upper eyelid and narrowness of the palpebral fissure. We surmised that an
      anatomical structure might exist in the preaponeurotic fat space, which
      determines the features of the Mongoloid eye. The upper eyelids of 720 Japanese
      patients and eight Japanese cadavers were macroscopically investigated, and
      sagittal slices of the central upper eyelid of one patient and nine cadavers were
      microscopically analysed. Another, lower-positioned transverse ligament different
      from the higher-positioned Whitnall's one was identified just above the fusional
      line between the orbital septum and the levator aponeurosis in almost every upper
      eyelid. A robust ligamentous structure was observed in 331 patients (46%) with
      puffier eyelids and a narrower palpebral fissure, a diaphanous retinaculum in 381
      patients (53%) and no transverse ligamentous tissue in eight patients (1%).
      Histological evaluation demonstrated that this ligament was composed of tight
      bundles of collagen fibres containing few elastic fibres. Examination of the
      preaponeurotic fat space indicated that the superficial expansion of the levator
      aponeurosis turned up around this transverse ligament to become the orbital
      septum. When the levator muscle contracts, the deep expansion of the levator
      aponeurosis retracts the tarsus, the middle expansion retracts the pretarsal
      orbicularis oculi muscle and skin, and the superficial expansion retracts the
      preaponeurotic fat against this ligament. This structure thus determines the low
      position of the preaponeurotic fat and restricts the vertical width of the
      palpebral fissure, causing the features of the Mongoloid eye.

PMID- 10927674
TI  - Use of orbicularis oculi muscle flap for undercorrected blepharoptosis with
      previous frontalis suspension.
AB  - The frontalis muscle and its fascia are connected with the orbicularis oculi
      muscle at the level of the eyebrow. Therefore, the superiorly based orbicularis
      oculi muscle flap, when advanced and attached to the tarsal plate, can
      dynamically elevate the upper lid and correct blepharoptosis with previous
      frontalis sling. Six patients with undercorrected blepharoptosis after frontalis
      sling suspension were included in this study. The superiorly based orbicularis
      oculi muscle flap was advanced to the tarsal plate in these patients and the
      redundant portion of the distal flap was resected. Postoperative results were
      satisfactory after 1-year follow-up.

PMID- 10927675
TI  - Left or right hand dominance in children with cleft lip and palate.
AB  - The relationship between unilateral cleft lip, bilateral cleft lip, palatal
      clefting and left-right hand dominance was studied in 337 patients with cleft lip
      and/or palate aged between 3 and 14 years. There was no statistically significant
      difference in the laterality of handedness between different types of cleft nor
      between unilateral left and right sided cleft lip with or without cleft palate.

PMID- 10927676
TI  - Patient satisfaction with Trilucent breast implants.
AB  - We report our findings in a retrospective study of patient satisfaction with
      soybean oil-filled mammary implants. Sixty-two women who had breast augmentation
      with Trilucent breast implants were sent a questionnaire to assess their
      satisfaction with implant placement; 19 of the 62 attended for clinical
      examination. Overall satisfaction with triglyceride implant placement was high:
      very pleased 45% (18/40), pleased 32.5% (13/40), content 12.5% (5/40). The
      majority of women felt that it had enhanced their body image and lifestyle
      (82.5%).

PMID- 10927677
TI  - The use of subatmospheric pressure dressing therapy to close lymphocutaneous
      fistulas of the groin.
AB  - Groin lymphorrhea is an uncommon but serious complication of vascular and cardiac
      surgery as well as interventional procedures that cannulate the femoral vessels.
      Treatment options are somewhat controversial. For lymphocutaneous fistulas, a
      commonly used current modality is early surgical ligation with the assistance of
      blue-dye staining of the lymphatic anatomy. The purpose of this case series is to
      give the first description of a new, less invasive, approach using subatmospheric
      pressure dressing therapy for the treatment of the challenging problem of
      lymphocutaneous fistulas of the groin.

PMID- 10927678
TI  - 'Jumping' cross finger flaps: a useful technique for salvaging parts in
      mutilating hand injuries.
AB  - In multi-digital injuries, soft tissue from non-adjacent injured fingers, which
      would have otherwise been discarded, can be used to cover small defects in
      salvageable digits. This was found useful in the salvage of four digits and one
      thumb. Anticipation of the need for a flap cover, and the possible availability
      of tissue in non-adjacent digits, is of paramount importance during the planning
      process in these injuries. This technique of using 'jumping' cross finger flaps
      is a useful method, when dealing with multiple finger mutilations that need soft
      tissue cover.

PMID- 10927679
TI  - The application of the rotation flap to the dorsum of the hand.
AB  - We have described the application of the rotation flap to the dorsum of the hand.
      This has proved useful for closing certain defects on the dorsum of the hand. The
      flap is designed as a rotation flap and the secondary defect is then closed by
      advancement using the laxity at the dorsal wrist crease. We have reported on 10
      cases. These adhere to the principle of repairing like with like and yield
      results which are both aesthetically and functionally excellent. The preservation
      of the axial elements of the flap theoretically makes it more robust and more
      resistant to infection.

PMID- 10927680
TI  - Large transverse fasciocutaneous leg flap: whole leg flap.
AB  - Large defects of leg and sole often need massive tissue transfer. As an
      alternative to microvascular transfer, we have developed a fasciocutaneous flap
      in which almost the whole of the skin of the opposite leg is transferred based
      just on the septocutaneous perforators of the posterior tibial artery. The flap
      has been used as a cross-leg fasciocutaneous flap with potential for use as a
      free flap by taking a segment of the posterior tibial artery. Our experience with
      11 cases is presented. Two patients suffered marginal necrosis while donor site
      problems were seen in another two patients. We have found this flap to be safe,
      technically easy and with minimal donor-site morbidity.

PMID- 10927681
TI  - Homodigital reverse pedicle island flap for reconstruction of the great toe.
AB  - A new homodigital reverse pedicle island flap is described for the reconstruction
      of the distal part of the great toe. It involves only a single stage procedure
      with minimal donor site morbidity and provides a good cosmetic result. Its use in
      two successful reconstructions is described.

PMID- 10927682
TI  - Effects of silicone gel sheet on the stratum corneum hydration.
AB  - Various groups have reported the efficacy of treatment with topical silicone gel
      sheet (SGS) for keloids and hypertrophic scars. Because its hydrating effect on
      the stratum corneum (SC) has been suggested as a mechanism underlying its
      therapeutic effectiveness, we evaluated it by comparing it with simple plastic
      film occlusion. With biophysical instruments we assessed the water content of the
      skin surface as well as its water evaporation on the flexor aspects of bilateral
      forearms of 10 healthy volunteers for 30min after removal of dressings of SGS or
      a plastic film that were applied either for 1 day or for 7 days. Occlusion with
      SGS or plastic film induced hydration of the skin surface, which was followed by
      an initial quick and later slow process of dehydration when the skin was exposed
      to the ambient atmosphere. The magnitude of the increase in hydration induced by
      SGS was always smaller than that of the plastic film occlusion and, unlike the
      latter treatment, hydration became less with repetition of SGS treatment. On day
      7, the SC hydration quickly reduced to the level of non-treated control skin
      after removal of the dressings. An in vivo test demonstrated that the water
      holding capacity of the SC normalised after 7 days of SGS treatment. SGS probably
      produces a favourable condition for the skin by protecting it from various
      environmental stimuli, while keeping the SC in an adequately but not over
      hydrated condition.

PMID- 10927683
TI  - Prefabrication of an axial bio-synthetic flap for circumferential tracheal defect
      reconstruction.
AB  - The aim of this study was to prefabricate an axial bio-synthetic flap for
      reconstruction of circumferential tracheal defects in a rabbit model. Two series
      of experiments were performed. In the first set of experiments axial island bio
      synthetic flaps were prefabricated. These consisted of an inner island de
      epithelialised fasciocutaneous flap from a rabbit's ear and an outer
      polytetrafluoroethylene vascular graft. The flaps were buried at the base of the
      rabbit's ear for periods of 1, 2 and 3 weeks (groups A, B and C, respectively),
      10 flaps per group. Only one flap in group C failed to survive. Clinical and
      histological assessment, at the completion of each time period, showed that only
      the viable flaps of group C developed all the characteristics needed for a
      tracheal substitute. In the second set of experiments the prefabricated bio
      synthetic flaps were transferred to the rabbit's neck by means of microvascular
      anastomoses. Ten such free flaps were buried at the rabbit's neck for 3 weeks
      (group D). Eight of the flaps remained viable and all the viable flaps had
      characteristics similar to those of group C. These results demonstrate the
      feasibility of creating a prefabricated axial bio-synthetic flap (island or
      free), over a 3-week period, possessing the characteristics needed for a tracheal
      substitute in a rabbit model.

PMID- 10927685
TI  - Trans-osseous passage of head and neck brachytherapy tubes.
AB  - Brachytherapy following surgical resection of head and neck malignancy is a
      useful adjunct if full dose external beam radiotherapy has been performed
      previously. Percutaneous tube placement has been described but accurate placement
      can be technically difficult in certain areas of the head and neck. A case report
      is presented of trans-osseous brachytherapy tube placement through the zygoma
      bone to allow for optimum surgical bed irradiation without kinking of the tubes.
      It is proposed that the trans-osseous placement is a useful technique when siting
      of the tubes is difficult.

PMID- 10927684
TI  - Time course of superoxide anion radicals generation in two ischaemia-reperfusion
      models: comparison between hindlimb replant model and isolated rectus femoris
      muscle model.
AB  - We examined differences in superoxide radical (O(2)(-)) production between a
      hindlimb replant model and isolated rectus femoris muscle model using rabbits.
      Using Japanese white rabbit hindlimbs, we made limb replant models (LR group: n =
      10) and isolated rectus femoris muscle models (IM group: n = 8) by temporary 4-h
      clampings of femoral vessels and nutrient vessels, respectively. For sham control
      subjects, the same surgical procedures with no clampings in both models were done
      (Control-LR: n = 7, Control-IM: n = 6). The measurement of O(2)(-)was performed
      by our chemiluminescence (CLN) method. In both models, reperfused blood samples
      were collected before reperfusion, and 5, 15, 30 and 60 min after reperfusion,
      and CLN was measured. We defined the superoxide index (SI) in each individual
      specimen as post-reperfusion CLN/pre-reperfusion CLN. The time course of SI in
      the Control-LR group was significantly higher than that of SI in the Control-IM
      group (P< 0.05). There was no significant difference between the time course of
      SI in the LR group and that of SI in the IM group. Both the limb replant model
      and isolated muscle model are applicable for the evaluation of radical formation
      in the reperfused stage though there are potential differences between the two
      models caused by the surgical procedures themselves.

PMID- 10927686
TI  - Phenytoin induced rhinophyma treated by excision and full thickness skin
      grafting.
AB  - A 49-year-old man suffering from post-traumatic epilepsy presented with a severe
      rhinophyma probably induced by phenytoin. Initial surgical shaving was soon
      followed by recurrence, formation of intraepidermal cysts and persistent
      infection. Ultimate treatment by full thickness excision and a full thickness
      skin graft resulted in a pleasing cosmetic result. Radical excision of the
      affected skin followed by full thickness skin graft nasal reconstruction should
      be considered for cases of recurrent severe rhinophyma with inclusion cysts to
      eradicate chronic infection and improve cosmesis.

PMID- 10927687
TI  - Successful free flap transfer following venous thrombectomy in recipient vessel.
AB  - We report the case of a 53-year-old male patient who suffered a high velocity
      multiple trauma with bilateral open tibial fractures. At definitive orthopaedic
      and plastic surgical reconstruction 5 days post initial trauma, he was found
      peroperatively to have an existing deep venous thrombosis in his popliteal vein
      on one side. He underwent venous thrombectomy and had subsequent successful
      latissimus dorsi flap transfer using the unblocked popliteal vein as a recipient
      vessel.

PMID- 10927688
TI  - Repair of a giant inguinoscrotal hernia.
AB  - We present a case of a long-standing, giant inguinoscrotal hernia extending to
      the patient's knees, complicated by intestinal obstruction. Initial management
      involved conservative treatment of the intestinal obstruction and optimising the
      patient's general condition. Surgical treatment included debulking the contents
      of the hernia sac by performing a right hemicolectomy and a small bowel
      resection, and reconstruction of the abdominal wall using Marlex mesh and a
      tensor fasciae latae flap. Although abdominal wall reconstruction for massive
      ventral or incisional herniae is well reported, inguinoscrotal herniae of this
      magnitude are much rarer and pose additional problems, which are discussed in
      this paper.

PMID- 10927689
TI  - Combined latissimus dorsi musculocutaneous flap and free superior gluteal artery
      skin flap.
AB  - We used a combined superior gluteal artery skin flap and latissimus dorsi
      musculocutaneous flap to repair a massive tissue defect of the upper limb. This
      combined flap has several advantages in that the length can be more than 60 cm,
      it can be used as an auxilliary muscle (latissimus dorsi) and it can also be used
      as a sensory flap. This combined flap is useful for covering massive skin
      defects.

PMID- 10927690
TI  - The use of the photoplethysmograph to monitor the training of a cross-leg free
      flap prior to division.
AB  - The cross-leg free flap is an important, although rarely used, option in the
      reconstruction of lower limb trauma. We report the use of photoplethysmography in
      the assessment of such a flap's training and the time of pedicle division.

PMID- 10927691
TI  - Sprouting epidermoid cysts.
AB  - Five unusually shaped (i.e. 'sprouting') epidermoid cysts in the upper lip, elbow
      and foot are reported. The tumours seldom produced symptoms. The maximum diameter
      was 25-48 mm. The complete removal including a sprouting bud is necessary.
      Histologically, partial to complete cyst wall rupture was recognised. A pulsion
      diverticulum due to variations in the thickness and strength of the cyst wall, a
      foreign body reaction against inner keratinous mass without obvious bacterial
      infection, and/or outer fibrous band(s) acting as constriction band(s), are
      proposed as possible causes of the 'sprouting'.

PMID- 10927692
TI  - Malignant melanoma and hormone replacement therapy.

PMID- 10927693
TI  - An objective outcome measure in reduction mammaplasty.

PMID- 10927694
TI  - The influence of the helium-neon laser irradiation on the viability of skin flaps
      in the rat.

PMID- 10927695
TI  - Informed consent.

PMID- 10927696
TI  - Meningococcal septicaemia in plastic surgery - a surgery for management.

PMID- 10927697
TI  - Endoscopic assisted otoplasty: a preliminary report.

PMID- 10927699
TI  - Notices

PMID- 10927698
TI  - Reconstruction of perianal skin defect using a V-Y advancement of bilateral
      gluteus maximus musculocutaneous flaps.

PMID- 10927700
TI  - Special selection: minocycline-induced hyperpigmentation of the tongue.

PMID- 10927701
TI  - Depression management programs.

PMID- 10927702
TI  - Depression management programs

PMID- 10927704
TI  - Informed consent for postfertilization effects of hormonal and surgical forms of
      birth control for women

PMID- 10927703
TI  - Informed consent for postfertilization effects of hormonal and surgical forms of
      birth control for women.

PMID- 10927706
TI  - Author's comment

PMID- 10927705
TI  - Health food store recommendations for breast cancer patients.
AB  - CONTEXT: Despite cancer patients' widespread and growing use of complementary and
      alternative medicine, minimal attention has been paid to the role of health food
      stores in the "supply side" of this phenomenon. OBJECTIVE: To gain a better
      understanding of health food store personnel's recommendations for breast cancer
      patient care. DESIGN: Researcher posing as the daughter of a breast cancer
      patient and surveying health food store personnel on their product
      recommendations for cancer care. SETTING: Oahu, Hawaii, summer 1998.
      PARTICIPANTS: All health food stores (N = 40) offering products for cancer
      patients. MAIN OUTCOME MEASURES: Recommended products and services, proposed
      mechanism of action, and costs. RESULTS: Store personnel readily provided
      information and product recommendations, with shark cartilage being the most
      frequent. Suggested mechanisms of action drew on traditional healing, scientific,
      and pseudoscientific rationales. Costs for recommended dosages varied multifold
      across stores and brands. CONCLUSIONS: Retailers supplying supplements can play
      an important role in the network of "authorities" for patients with breast and
      other cancers, as they readily provide advice and recommend products. The reasons
      why patients seek health food store remedies are useful in developing approaches
      to patient education. Physicians and other providers are in a key position to
      assist cancer patients in making informed choices when considering health store
      products.

PMID- 10927708
TI  - Improvement of outcomes in chronic illness.

PMID- 10927707
TI  - Efficacy of nurse telehealth care and peer support in augmenting treatment of
      depression in primary care.
AB  - BACKGROUND: Primary care treatment of depression needs improvement. OBJECTIVE: To
      evaluate the efficacy of 2 augmentations to antidepressant drug treatment.
      DESIGN: Randomized trial comparing usual care, telehealth care, and telehealth
      care plus peer support; assessments were conducted at baseline, 6 weeks, and 6
      months. SETTING: Two managed care adult primary care clinics. PARTICIPANTS: A
      total of 302 patients starting antidepressant drug therapy. INTERVENTIONS: For
      telehealth care: emotional support and focused behavioral interventions in ten 6
      minute calls during 4 months by primary care nurses; and for peer support:
      telephone and in-person supportive contacts by trained health plan members
      recovered from depression. MAIN OUTCOME MEASURES: For depression: the Hamilton
      Depression Rating Scale and the Beck Depression Inventory; and for mental and
      physical functioning: the SF-12 Mental and Physical Composite Scales and
      treatment satisfaction. RESULTS: Nurse-based telehealth patients with or without
      peer support more often experienced 50% improvement on the Hamilton Depression
      Rating Scale at 6 weeks (50% vs 37%; P =.01) and 6 months (57% vs 38%; P =.003)
      and on the Beck Depression Inventory at 6 months (48% vs 37%; P =. 05) and
      greater quantitative reduction in symptom scores on the Hamilton scale at 6
      months (10.38 vs 8.12; P =.006). Telehealth care improved mental functioning at 6
      weeks (47.07 vs 42.64; P =.004) and treatment satisfaction at 6 weeks (4.41 vs
      4.17; P =.004) and 6 months (4.20 vs 3.94; P =.001). Adding peer support to
      telehealth care did not improve the primary outcomes. CONCLUSION: Nurse
      telehealth care improves clinical outcomes of antidepressant drug treatment and
      patient satisfaction and fits well within busy primary care settings.

PMID- 10927710
TI  - Editor's comment: cost-effectiveness of the conventional papanicolaou test with a
      new adjunct to cytological screening for squamous cell carcinoma of the uterine
      cervix and its precursors

PMID- 10927709
TI  - Cost-effectiveness of the conventional papanicolaou test with a new adjunct to
      cytological screening for squamous cell carcinoma of the uterine cervix and its
      precursors.
AB  - OBJECTIVE: To estimate costs and outcomes of conventional annual Papanicolaou
      (Pap) test screening compared with biennial Pap test plus speculoscopy (PPS)
      screening for cervical neoplasms. DESIGN: A Markov model compared cost
      effectiveness and outcomes of annual Pap tests with biennial PPS. The model
      includes direct costs of screening, diagnostic testing, and treatment for
      squamous intraepitheial lesions and invasive cancers; indirect costs (eg, lost
      productivity because of cervical cancer); and newer management practices,
      including human papillomavirus DNA testing. PATIENTS: Women aged 18 to 64 years.
      INTERVENTION: Screening for cervical neoplasms with either annual Pap smear test
      or biennial PPS. MAIN OUTCOME MEASURE: Marginal cost per life-year gained.
      RESULTS: The probability of women having squamous intraepithelial lesions,
      cervical cancer, or death from cervical cancer was lower among women undergoing
      PPS biennially. A total of 12 additional days of life per woman was gained with
      biennial PPS during the 47-year model period. Total average cumulative direct
      medical costs per patient were $1419 for biennial PPS compared with $1489 for
      annual Pap tests. Total costs, including direct medical costs and indirect costs,
      were $2185 for PPS compared with $3179 for Pap tests alone. Increased savings and
      patient outcomes were observed in high-risk populations. CONCLUSION: Our
      simulations indicate that biennial screening with PPS is expected to provide cost
      savings for women older than 18 years compared with annual Pap test screening,
      especially for those in high-risk populations.

PMID- 10927711
TI  - Costs of beta-lactam allergies: selection and costs of antibiotics for patients
      with a reported beta-lactam allergy.
AB  - OBJECTIVE: To evaluate antibiotic selection and the cost effect of reported beta
      lactam allergies. DESIGN: Retrospective medical records review comparing
      antimicrobial selection and costs in patients with a reported beta-lactam allergy
      with a group in which no such allergy had been documented. SETTING: University
      based family medicine clinic. PATIENTS: Patients who were prescribed at least 1
      antibiotic for an upper respiratory tract infection, otitis media, sinusitis,
      and/or a urinary tract infection were eligible. One thousand two hundred one
      patients were identified via ICD-9-CM (International Classification of Diseases,
      Ninth Revision, Clinical Modification) codes. Four hundred sixty-five patients
      were initially identified and an additional 195 family members were eligible for
      inclusion. MAIN OUTCOME MEASURES: Comparison of antimicrobial selection and costs
      (by average wholesale price) between patients with and without a reported beta
      lactam allergy. RESULTS: Of the 660 patients eligible for inclusion, 99 (15%) had
      a documented beta-lactam allergy. Of the patients with a documented allergy, only
      33% had a description of their purported reaction. The mean antibiotic cost for
      patients with a beta-lactam allergy was significantly higher compared with those
      without a beta-lactam allergy ($26.81 vs $16.28, respectively; P =.004). Patients
      with a beta-lactam allergy were more likely to have received a cephalosporin,
      macrolide, or a miscellaneous agent (eg, quinolone, tetracycline, or
      nitrofurantoin) (P =.001). CONCLUSIONS: Patients with a beta-lactam allergy had
      higher antibiotic costs and were more likely to receive a broader-spectrum
      antibiotic. Most patients with a reported allergy did not have a description of
      their reaction. Skin testing may be of use in detecting true beta-lactam
      allergies; however, further study is needed to determine its cost-effectiveness.

PMID- 10927713
TI  - Editor's comment: is caffeine a flavoring agent in cola soft drinks?

PMID- 10927712
TI  - Is caffeine a flavoring agent in cola soft drinks?
AB  - BACKGROUND: Concern has been expressed about the nutrition and health impact of
      high rates of soft drink consumption. Caffeine is an added ingredient in
      approximately 70% of soft drinks consumed in the United States. The soft drink
      manufacturers' justification to regulatory agencies and the public for adding
      caffeine to soft drinks is that caffeine is a flavoring agent. OBJECTIVE: To
      examine the claim that caffeine plays an integral role in the flavor profile of
      soft drinks, by examining the effect of caffeine on the threshold for detection
      of flavor differences in cola beverages. DESIGN: Double-blind crossover study
      starting November 1998 and ending July 1999. SETTING: An academic research
      center. PARTICIPANTS: Twenty-five adult regular consumers of cola soft drinks.
      Based on a screening session, all were able to detect a flavor difference between
      cola containing sugar and diet cola. INTERVENTION: A sensitive version of a
      forced-choice flavor-detection procedure was used to evaluate the effects of a
      wide range of caffeine concentrations (range, 0.05-1.6 mg/mL) on the ability to
      detect flavor differences between caffeinated and caffeine-free cola beverages.
      Repeated tests permitted determination of significant detection at each
      concentration in individual subjects. MAIN OUTCOME MEASURES: Percentage of
      subjects significantly detecting a flavor difference and mean percentage of
      trials correct at each caffeine concentration. RESULTS: Detection of flavor
      differences increased as a function of caffeine concentration. At the 0.1-mg/mL
      concentration, which is the approximate concentration in the majority of cola
      soft drink products, 2 subjects (8%) significantly detected a flavor difference
      and the mean percentage correct (53%) was at chance levels. CONCLUSIONS: The
      finding that only 8% of a group of regular cola soft drink consumers could detect
      the effect of the caffeine concentration found in most cola soft drinks is at
      variance with the claim made by soft drink manufacturers that caffeine is added
      to soft drinks because it plays an integral role in the flavor profile. It is
      valuable for the general public, the medical community, and regulatory agencies
      to recognize that the high rates of consumption of caffeinated soft drinks more
      likely reflect the mood-altering and physical dependence-producing effects of
      caffeine as a central nervous system-active drug than its subtle effects as a
      flavoring agent. Arch Fam Med. 2000;9:727-734

PMID- 10927714
TI  - Management of nasal fractures.
AB  - The nasal bones are the most commonly fractured bones in the body. Accurate
      diagnosis and appropriate surgical intervention are key in the management of
      nasal fractures. While these injuries are not life-threatening, mismanagement of
      nasal fractures can lead to both aesthetic and functional deformities. A thorough
      history and careful physical examination are adequate for the diagnosis of nasal
      fractures. Literature in the field does not support the use of x-ray films to aid
      in the diagnosis. The majority of injuries are seen after significant edema
      becomes present and cannot be accurately reduced at that time. Therefore, with
      the exception of grossly displaced fractures, open fractures, and septal
      hematomas, most nasal fractures should be definitively treated after 3 to 10 days
      once swelling has resolved. This article will review pertinent nasal anatomic
      structure, pathophysiological characteristics of nasal fractures, diagnostic
      techniques, treatment modalities, and common controversies associated with nasal
      fractures.

PMID- 10927715
TI  - Update on the management of hyperthyroidism and hypothyroidism.

PMID- 10927716
TI  - SOAP: solutions to often asked problems. Choice of antihistamines for urticaria.

PMID- 10927718
TI  - Editor's comment: evaluation of Migraineurs' preferences for naratriptan over
      conventional first-line agents

PMID- 10927719
TI  - A pilot study examining patient response to a weight loss workbook designed to Be
      used in a family medicine outpatient setting.
AB  - This study measured patient response to a self-help weight loss workbook designed
      for use in an outpatient, family medicine practice. The primary measures were 2
      follow-up telephone calls, the first at 1 week and the second at 1 month after
      the book was given to the patient. Initially, patients were enthusiastic about
      the book and had read it, and 24 (70%) intended to use it. On the other hand, at
      1 month, only 8 (32%) of those called were actually using the book. Reasons for
      this change are explored.

PMID- 10927717
TI  - Evaluation of migraineurs' preferences for naratriptan over conventional first
      line agents.
AB  - OBJECTIVE: To assess patient satisfaction with and preference for naratriptan
      hydrochloride therapy over previous "nontriptan" therapy for migraines. DESIGN
      AND SETTING: Open-label study conducted at 15 primary care clinics. PATIENTS: One
      hundred forty-three adults meeting International Headache Society diagnostic
      criteria for migraine who were not using triptans as first-line therapy for
      migraines were enrolled; 115 completed the study. INTERVENTION AND OUTCOME
      ASSESSMENTS: At baseline, satisfaction with current migraine therapy was
      assessed. Patients were provided with naratriptan hydrochloride, 2.5 mg, to treat
      3 migraines and diaries to record headache symptoms and response to treatment.
      After treating 3 migraines, satisfaction with naratriptan therapy and preference
      for either previous or naratriptan therapy were assessed. RESULTS: Eighty-nine
      (62%) of 143 patients had previous exposure to triptans, with lack of prescribing
      (55%) as the primary reason for not continuing their use as first-line therapy.
      Medications used for first-line therapy included simple analgesics (59%),
      combination products (46%), and narcotics (13%). After treating 3 migraines with
      naratriptan, satisfaction with migraine therapy increased from 47% to 75%. Sixty
      three percent of patients preferred naratriptan therapy over their previous
      nontriptan therapy, 27% preferred their previous therapy, and 10% had no
      preference. The main reasons for preference for naratriptan therapy were
      "relieves pain effectively" (86%) and "restores ability to function/perform task"
      (81%). CONCLUSION: Naratriptan for first-line migraine therapy was preferred by
      most patients over previous nontriptan therapy.

PMID- 10927720
TI  - Case of the month: what killed the patient-the disease or the experimental
      treatment?

PMID- 10927721
TI  - Is the therapeutic nature of the patient-physician relationship being undermined?
      A primary care physician's perspective.

PMID- 10927722
TI  - The role of hormone replacement therapy in the prevention of postmenopausal heart
      disease.
AB  - Coronary heart disease is the single leading cause of death in women and a
      significant cause of disability. Menopause adversely affects several risk factors
      for coronary heart disease, suggesting that hormones influence the risk of
      coronary heart disease in postmenopausal women. This article reviews the
      observational and clinical trial data evaluating the relation between
      cardiovascular disease and hormone replacement therapy. Biological mechanisms of
      estrogen and the impact of adding progestins are emphasized. Potential risks and
      benefits of therapy are discussed. The relative effects of other estrogen and
      lipid-lowering therapies for preventing coronary heart disease in postmenopausal
      women are highlighted.

PMID- 10927723
TI  - Long-term safety of hepatic hydroxymethyl glutaryl coenzyme A reductase
      inhibitors: the role of metabolism-monograph for physicians.

PMID- 10927724
TI  - Self-reported hypertension treatment practices among primary care physicians:
      blood pressure thresholds, drug choices, and the role of guidelines and evidence
      based medicine.
AB  - BACKGROUND: Primary care physician treatment practices affect the rate of
      hypertension control to the goal of 140/90 mm Hg. Awareness of and agreement with
      national hypertension management guidelines, and grounding in evidence-based
      medicine principles, may be important determinants of practice. METHODS: A 26
      item mail questionnaire was sent to a national sample of 1200 primary care
      physicians. The questionnaire elicited (1) the blood pressure (BP) criteria
      physicians use to initiate and intensify hypertension treatment, (2) first-line
      drug treatment choices, (3) familiarity with the Joint National Committee on
      Detection, Evaluation, and Treatment of High Blood Pressure (JNC) hypertension
      treatment guidelines, and (4) familiarity with research methods used to develop
      evidence-based medicine guidelines. The analysis focused on (1) determining the
      percentage of physicians who reported treatment practices consistent with JNC
      recommendations and (2) the relation between familiarity with JNC guidelines,
      evidence-based medicine methods, and reported treatment practices. RESULTS: The
      overall response rate was 34%, with no important differences in demographic or
      professional training variables between respondents and nonrespondents. For
      middle-aged patients with uncomplicated hypertension, 33% of physicians would not
      start drug therapy unless the diastolic BP was greater than 95 mm Hg, and 43%
      would not start unless the systolic BP was greater than 160 mm Hg. In patients
      without complications who were receiving drug treatment, 25% of physicians would
      not intensify therapy for a persistent diastolic BP of 94 mm Hg, and 33% would
      not intensify therapy for a systolic BP of 158 mm Hg. Physicians were generally
      less aggressive in older patients. Angiotensin-converting enzyme inhibitors were
      the most common first-line drug choice. Forty-one percent of physicians had not
      heard of or were not familiar with the JNC guidelines. In multiple logistic
      regression models, familiarity with the JNC guidelines was associated with lower
      treatment thresholds, and increased familiarity with research methods was
      associated with greater use of diuretics or beta-blockers as first-line agents.
      CONCLUSIONS: Many physicians have higher BP thresholds for the diagnosis and
      treatment of hypertension than the 140/90 mm Hg criterion recommended by the JNC.
      Therefore, further improvements in population hypertension control will require
      physician behavior change. Physician practice is associated with awareness of
      practice guidelines and familiarity with evidence-based medicine methods, but the
      precise nature and extent of this relation requires further study.

PMID- 10927725
TI  - Association of hypertension and sleep-disordered breathing.
AB  - BACKGROUND: To our knowledge, the association between sleep-disordered breathing
      (SDB) and hypertension has not been evaluated in subjects from the general
      population with a wide age range while adjusting for the possible confounding
      factors of age, body mass index, sex, menopause and use of hormone replacement
      therapy, race, alcohol use, and smoking. METHODS: In the first phase of this
      study, we interviewed 4364 men and 12,219 women, aged 20 to 100 years. In the
      second phase of this study, 741 men and 1000 women, previously interviewed, were
      selected based on the presence of risk factors for SDB (snoring, daytime
      sleepiness, obesity, hypertension, and, for women, menopause). Each subject
      selected for the second phase of the study provided a comprehensive history,
      underwent a physical examination, and was evaluated for 1 night in the sleep
      laboratory. In terms of severity of SDB, 4 groups were identified: moderate or
      severe (obstructive apnea/hypopnea index > or =15.0), mild (snoring and an
      obstructive apnea/hypopnea index of 0.1-14.9), snoring, and no SDB, the control
      group. RESULTS: Sleep-disordered breathing was independently associated with
      hypertension when potential confounders were controlled for in the logistic
      regression analysis. The strength of this association decreased with age and was
      proportional to the severity of SDB. In the best-fitted model, neither sex nor
      menopause changed the relationship between hypertension and SDB. CONCLUSIONS: In
      the results of this study, SDB, even snoring, was independently associated with
      hypertension in both men and women. This relationship was strongest in young
      subjects, especially those of normal weight, a finding that is consistent with
      previous findings that SDB is more severe in young individuals.

PMID- 10927726
TI  - Strong and significant relationships between aggregation of major coronary risk
      factors and the acceleration of carotid atherosclerosis in the general population
      of a Japanese city: the Suita Study.
AB  - BACKGROUND: Carotid arterial intimal-medial thickness (IMT) measured by high
      resolution B-mode ultrasonography has come to be used as a noninvasive surrogate
      end point to measure progression of atherosclerosis. However, there are no
      detailed data on the relationship between aggregation of coronary risk factors
      and carotid atherogenesis. METHODS: Cross-sectional assessment of the
      relationship between carotid atherosclerosis detected by high-resolution
      ultrasonography and integration of major coronary risk factors by age and sex.
      Subjects aged 30 to 86 years were randomly selected from Suita, located in Osaka,
      the second largest urban area of Japan, including 1896 men and 2102 women.
      Carotid atherosclerosis was evaluated by using our atherosclerotic indexes of
      IMT, plaque number, plaque score, and percentage of stenosis of the carotid
      artery assessed using ultrasonography by sex and age group classified by number
      of major coronary risk factors (ie, hypertension [diastolic blood pressure > or
      =90 mm Hg and/or systolic blood pressure > or 140 mm Hg or receiving medication],
      smoking [current smoker], and hypercholesterolemia [serum total cholesterol level
      > or =5.68 mmol/L [220 mg/dL] or receiving medication]). RESULTS: The mean
      carotid atherosclerotic index value, especially the mean IMT value, of the
      subjects with 1 major coronary risk factor was on average 0.028 mm (3.2%) higher
      for men and 0.025 mm (2.9%) higher for women than that of the subjects without
      major coronary risk factors; for subjects with 2 risk factors, 0.054 mm (6.3%)
      higher for men and 0.053 mm (6.2%) higher for women; and for high-risk subjects
      with 3 major risk factors, 0.135 mm (15.8%) higher for men and 0.137 mm (15.4%)
      higher for women. The percentage of the subjects with severe stenosis of at least
      50% increased stepwise with increases in the number of coronary risk factors and
      showed a significant difference (P<.05) between men and women, ie, 2.4% vs 0. 6%
      (P =.01) among the subjects with no risk factors; 6.7% vs 1.5% (P<.001), subjects
      with 1 risk factor; 10.7% vs 2.7% (P<.001), subjects with 2 risk factors; and
      18.6% vs 5.0% (P =.01), high-risk subjects. CONCLUSIONS: Aggregation of
      established major coronary risk factors strongly influenced carotid atherogenesis
      in both sexes. There were significant differences between sexes in the
      acceleration or progression of carotid atherosclerosis.

PMID- 10927728
TI  - Risk of hepatitis C transmission from infected medical staff to patients: model
      based calculations for surgical settings.
AB  - CONTEXT: Concern is increasing in both the medical community and among the
      general public about the possible transmission of hepatitis C virus (HCV) from
      infected health care workers to their patients. Until now, no reliable estimates
      for the risk of such transmission exist. OBJECTIVE: To estimate the probability
      of HCV transmission from a surgeon to a susceptible patient during invasive
      procedures. DESIGN: A model consisting of 4 probabilities was used: (A) the
      probability that the surgeon is infected with HCV, (B) the probability that the
      surgeon might contract percutaneous injuries, (C) the probability that an HCV
      contaminated instrument will recontact the wound, and (D) the probability of HCV
      transmission after exposure. Values for the calculations were taken from
      published studies. RESULTS: When the surgeon's HCV status is unknown, the risk of
      HCV transmission during a single operation is 0.00018% +/- 0.00002% (mean +/-
      SD). If the surgeon is HCV RNA positive, this risk equals 0.014% +/- 0.002%. The
      likelihoods of transmission in at least 1 of 5000 invasive procedures performed
      by a surgeon during 10 years are 0.9% +/- 0.1% (HCV status unknown) and 50.3% +/-
      4.8% (HCV RNA positive), respectively. CONCLUSIONS: The calculated risks for HCV
      transmission from a surgeon to a susceptible patient during a single invasive
      procedure are comparable to the chance of acquiring HCV by receiving a blood
      transfusion. These figures could provide a basis for further discussions on this
      controversial subject and might also be relevant for future recommendations on
      the management of HCV-infected health care workers.

PMID- 10927727
TI  - A randomized controlled trial of auricular acupuncture for cocaine dependence.
AB  - BACKGROUND: Partly because of a lack of a conventional, effective treatment for
      cocaine addiction, auricular acupuncture is used to treat this disorder in
      numerous drug treatment facilities across the country for both primary cocaine
      dependent and opiate-dependent populations. OBJECTIVE: To evaluate the
      effectiveness of auricular acupuncture for the treatment of cocaine addiction.
      METHODS: Eighty-two cocaine-dependent, methadone-maintained patients were
      randomly assigned to 1 of 3 conditions: auricular acupuncture, a needle-insertion
      control condition, or a no-needle relaxation control. Treatment sessions were
      provided 5 times weekly for 8 weeks. The primary outcome was cocaine use assessed
      by 3-times-weekly urine toxicology screens. RESULTS: Longitudinal analysis of the
      urine data for the intent-to-treat sample showed that patients assigned to
      acupuncture were significantly more likely to provide cocaine-negative urine
      samples relative to both the relaxation control (odds ratio, 3.41; 95% confidence
      interval, 1.33-8.72; P =. 01) and the needle-insertion control (odds ratio, 2.40;
      95% confidence interval, 1.00-5.75; P =.05). CONCLUSIONS: Findings from the
      current study suggest that acupuncture shows promise for the treatment of cocaine
      dependence. Further investigation of this treatment modality appears to be
      warranted.

PMID- 10927729
TI  - Lying to each other: when internal medicine residents use deception with their
      colleagues.
AB  - BACKGROUND: While lying is morally problematic, physicians have been known to use
      deception with their patients and with third parties. Little is known, however,
      about the use of deception between physicians. OBJECTIVES: To determine the
      likelihood that resident physicians say they would deceive other physicians in
      various circumstances and to examine how variations in circumstances affect the
      likelihood of using deception. METHODS: Two versions of a confidential survey
      using vignettes were randomly distributed to all internal medicine residents at 4
      teaching hospitals in 1998. Survey versions differed by introducing slight
      variations to each vignette in ways we hypothesized would influence respondents'
      willingness to deceive. The likelihood that residents say they would use
      deception in response to each vignette was compared between versions. RESULTS:
      Three hundred thirty surveys were distributed (response rate, 67%). Of those who
      responded, 36% indicated they were likely to use deception to avoid exchanging
      call, 15% would misrepresent a diagnosis in a medical record to protect patient
      privacy, 14% would fabricate a laboratory value to an attending physician, 6%
      would substitute their own urine in a drug test to protect a colleague, and 5%
      would lie about checking a patient's stool for blood to cover up a medical
      mistake. For some of the scenarios, the likelihood of deceiving was influenced by
      variations in the vignettes. CONCLUSIONS: A substantial percentage of internal
      medicine residents report they would deceive a colleague in various
      circumstances, and the likelihood of using deception depends on the context.
      While lying about clinical issues is not common, it is troubling when it occurs
      at any time. Medical educators should be aware of circumstances in which
      residents are likely to deceive, and discuss ways to eliminate incentives to lie.

PMID- 10927730
TI  - Low-molecular-weight and unfractionated heparin for prevention of venous
      thromboembolism in neurosurgery: a meta-analysis.
AB  - BACKGROUND: Venous thromboembolism is a common, life-threatening complication in
      neurosurgery, but prophylaxis with anticoagulant agents has not gained wide
      acceptance because of concern about intracranial bleeding. We performed a meta
      analysis of controlled randomized trials on the efficacy and safety of heparin in
      the prophylaxis of venous thromboembolism in neurosurgery. OBJECTIVE: To review
      the clinical benefit of prophylaxis of venous thromboembolism with heparin in the
      controversial setting of neurosurgery. METHODS: Relevant trials evaluating
      heparin for prophylaxis of venous thromboembolism in neurosurgery were identified
      by a MEDLINE search, scan of meeting abstracts, and scrutiny of the references of
      original articles and reviews. Four controlled randomized studies, 3 of which
      involved low-molecular-weight heparin, were included in the analysis, and 4
      uncontrolled studies are commented on in the article. The outcome measure
      (observed minus expected number of events) and its variance were calculated for
      each single trial and then summed. Two-tailed P values and 95% confidence
      intervals (CIs) were calculated. Efficacy was assessed per protocol and safety by
      intention-to-treat analysis. The homogeneity of the studies was tested with the
      chi(2) statistic. The results were also expressed as number needed for 1 extra
      event. RESULTS: A total of 187 thromboembolic events were recorded in 827
      patients (22.6%). Heparin prophylaxis resulted in a 45% relative risk reduction
      of venous thromboembolic events (odds ratio [OR], 0.48; 95% CI, 0.35-0.66; P<.
      001). Nineteen major bleedings were recorded in 1022 patients. None were fatal.
      Heparin treatment resulted in a 71% relative risk increase of major bleeding (OR,
      1.72; 95% CI, 0.69-4.27; P =.24). The number needed to treat was 7.7 for venous
      thromboembolism and 16 for proximal deep vein thrombosis. The number needed to
      harm was 102 (115 for low-molecular-weight heparin). CONCLUSIONS: Low-molecular
      weight and unfractionated heparin have been shown to be effective for prophylaxis
      of venous thromboembolism in elective neurosurgery without excessive bleeding
      risk.

PMID- 10927731
TI  - Who reports receiving advice to lose weight? Results from a multistate survey.
AB  - BACKGROUND: Overweight and obesity are increasingly prevalent in the United
      States. The prevalence of health care provider advice to lose weight is not
      clear. METHODS: We examined the percentage of individuals who reported being
      advised to lose weight by a health care practitioner in the past year by
      population subgroup. Participants were individuals in the 10 states participating
      in the 1996 Behavioral Risk Factor Surveillance System, which assessed advice to
      lose weight, hypertension awareness, and cholesterol awareness. RESULTS: The
      prevalence of reporting advice to lose weight was most strongly associated with
      body mass index (BMI) (calculated as weight in kilograms divided by the square of
      height in meters) and weight-related comorbidities. In individuals with a BMI of
      25 to 27, only 5.6% of those with no comorbidities and 13.6% of those with
      comorbidities received advice. These rates were increased to 32.4% and 47.3%,
      respectively, in those with a BMI greater than 30. Middle-aged individuals, those
      with more education, and those living in the northeast were also more likely to
      receive advice. Receiving advice to maintain weight was reported by only 2. 5% of
      respondents. Receiving advice to lose weight was strongly associated with trying
      to lose weight, especially in those with a BMI of 25 to 27, where 77.5% who
      received advice reported trying to lose weight vs 33.4% of those who did not
      receive advice. CONCLUSIONS: Advice to lose weight is uncommon and is given
      primarily to those who are already obese, are middle-aged, and have
      comorbidities. Practitioners may be missing important opportunities to counsel
      mildly overweight individuals to lose weight or to maintain their weight and
      thereby prevent comorbidities.

PMID- 10927732
TI  - Oral anticoagulation management in primary care with the use of computerized
      decision support and near-patient testing: a randomized, controlled trial.
AB  - BACKGROUND: There is increased pressure on primary care physicians to monitor
      oral anticoagulation. OBJECTIVE: To test the null hypothesis that oral
      anticoagulation care can be provided at least as well in primary care through a
      nurse-led clinic, involving near-patient testing and computerized decision
      support software, compared with routine hospital management based on a variety of
      clinical outcome measures. METHODS: A randomized, controlled trial in 12 primary
      care practices in Birmingham, England (9 intervention and 3 control). Two control
      populations were used: patients individually randomly allocated as controls in
      the intervention practices (intrapractice controls) and all patients in control
      practices (interpractice controls). Intervention practices' patients were
      randomized to the intervention (practice-based anticoagulation clinic) or control
      (hospital clinic) group. The main outcome measure was therapeutic control of the
      international normalized ratio. RESULTS: Three hundred sixty-seven patients were
      recruited (122 intervention patients, 102 intrapractice control patients, and 143
      interpractice control patients). Standard measures of control of the
      international normalized ratio (point prevalence) showed no significant
      difference between the intervention and control groups. Data on proportion of
      time spent in the international normalized ratio range showed significant
      improvement for patients in the intervention group (paired t test, P =.008).
      CONCLUSIONS: Nurse-led anticoagulation clinics can be implemented in novice
      primary care settings by means of computerized decision support software and near
      patient testing. Care given by this model is at least as good as routine hospital
      follow-up. The model is generalizable to primary health care centers operating in
      developed health care systems.

PMID- 10927733
TI  - Sex inequality in kidney transplantation rates.
AB  - BACKGROUND: Men in the United States undergoing renal replacement therapy are
      more likely than women to receive a kidney transplant. However, the ability to
      pay may, in part, be responsible for this finding. OBJECTIVE: To compare adult
      male and female transplantation rates in a setting in which equal access to
      medical treatment is assumed. METHODS: Using data from the Canadian Organ
      Replacement Register, the rate of first transplantations was computed for the 20,
      131 men and the 13,458 women aged 20 years or older who initiated renal
      replacement therapy between January 1, 1981, and December 31, 1996. Poisson
      regression analysis was used to estimate the male-female transplantation rate
      ratio, adjusting for age, race, province, calendar period, underlying disease
      leading to renal failure, and dialytic modality. Actuarial survival methods were
      used to compare transplantation probability for covariable-matched cohorts of men
      and women. RESULTS: Men experienced 20% greater covariable-adjusted kidney
      transplantation rates relative to women (rate ratio, 1.20; 95% confidence
      interval, 1.13-1.27). The sex disparity was stronger for cadaveric transplants
      (rate ratio, 1.23) compared with those from living donors (rate ratio, 1.10). The
      5-year probability of receiving a transplant was 47% for men and 39% for women
      within covariable-matched cohorts (P<.001). The sex disparity in transplantation
      rates increased with increasing age. The sex effect was weaker among whites and
      Oriental persons (Chinese, Japanese, Vietnamese, Cambodian, Laotian, Filipino,
      Malaysian, Indonesian, and Korean) and stronger among blacks, Asian Indians
      (Indian, Pakistani, and Sri Lankan), and North American Indians (aboriginal).
      CONCLUSION: Since survival probability and quality of life are superior for
      patients who undergo transplantation relative to those who undergo dialysis, an
      increased effort should be made to distribute kidneys available for
      transplantation more equitably by sex among patients undergoing renal replacement
      therapy.

PMID- 10927734
TI  - Bilateral leg edema, obesity, pulmonary hypertension, and obstructive sleep
      apnea.
AB  - BACKGROUND: Pulmonary hypertension is usually due to an underlying cardiac or
      pulmonary condition. An association between unexplained pulmonary hypertension
      and bilateral leg edema in primary care patients was found previously. We
      undertook this study to identify the frequency of obstructive sleep apnea (OSA)
      in ambulatory, adult patients with pulmonary hypertension who initially presented
      with bilateral leg edema. METHODS: Twenty ambulatory adults with bilateral leg
      edema, echocardiocardiographic evidence of pulmonary hypertension (estimated
      pulmonary artery systolic pressure >30 mm Hg) without left ventricular
      dysfunction, and no clinically apparent pulmonary disease [corrected] were
      enrolled from a suburban family practice and an inner-city family practice during
      a 3-year period. Spirometric assessment, pulse oximetry, rheumatologic
      evaluation, polysomnography, and questionnaire information regarding risk factors
      for pulmonary hypertension were obtained for each subject. RESULTS: Fifteen
      patients (75%) completed the study. Almost all of the subjects were obese. Nine
      (60%) of the 15 had OSA. None of the subjects demonstrated an obstructive pattern
      on spirometric evaluation results, but 9 (60%) had a restrictive spirometry
      pattern, consistent with their obesity. None of the subjects had daytime
      hypoxemia. Systemic hypertension was present in two-thirds of the subjects with
      OSA, and was absent in all of the subjects who lacked OSA. CONCLUSIONS: Bilateral
      leg edema in obese primary care patients is associated with both OSA and modest
      pulmonary hypertension. If these findings are generalizable, then bilateral leg
      edema may be an important clinical marker for underlying OSA.

PMID- 10927735
TI  - 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and the risk of
      cancer: a nested case-control study.
AB  - BACKGROUND: During the past 15 years there has been an exponential increase in
      the number of prescriptions for lipid-lowering drugs. Uncertainties remain about
      the long-term impact of these medications on cancer, which is particularly
      bothersome given that the duration of these treatments may extend for several
      decades. OBJECTIVE: To explore the association between 3-hydroxy-3-methylglutaryl
      coenzyme A (HMG-CoA) reductase inhibitors and cancer incidence. METHODS: Using
      the administrative health databases of the Regie de l'Assurance-Maladie du Quebec
      we performed a nested case-control study. We selected a cohort of 6721
      beneficiaries of the health care plan of Quebec who were free of cancer for at
      least 1 year at cohort entry, 65 years and older, and treated with lipid
      modifying agents. Cohort members were selected between 1988 and 1994 and were
      followed up for a median period of 2.7 years. From the cohort, 542 cases of first
      malignant neoplasm were identified, and 5420 controls were randomly selected.
      Users of HMG-CoA reductase inhibitors were compared with users of bile acid
      binding resins as to their risk of cancer. Specific cancer sites were also
      considered. RESULTS: Users of HMG-CoA reductase inhibitors were found to be 28%
      less likely than users of bile acid-binding resins to be diagnosed as having any
      cancer (rate ratio, 0.72; 95% confidence interval, 0.57-0.92). All specific
      cancer sites under study were found to be not or inversely associated with the
      use of HMG-CoA reductase inhibitors. CONCLUSION: The results of our study provide
      some degree of reassurance about the safety of HMG-CoA reductase inhibitors.

PMID- 10927736
TI  - Frequency of major hemorrhage in patients treated with unfractionated intravenous
      heparin for deep venous thrombosis or pulmonary embolism: a study in routine
      clinical practice.
AB  - BACKGROUND: The rate of major hemorrhage during the initial treatment with
      unfractionated heparin (UFH) in patients with deep venous thrombosis (DVT) and
      pulmonary embolism (PE) in routine clinical practice is understudied. In recent
      clinical trials an overall average of 3.8% was reported. However, the incidence
      of this complication in routine patient care might be higher owing to less strict
      patient selection and lack of standardization in the administration of heparin.
      We have determined major bleeding rates during heparin treatment for DVT or PE in
      routine practice and compared these rates with data from clinical trials.
      METHODS: Data on the occurrence of major hemorrhage were retrieved according to
      strict criteria from the records of patients who had received continuous
      intravenous UFH therapy to treat objectively documented DVT or PE in 3 hospitals.
      RESULTS: After exclusion of 29 patients because of lack of objective diagnosis of
      DVT or PE and 25 patients because of initial treatment with low-molecular-weight
      heparin, 424 consecutive patients were available for detailed analysis. Among
      them, 17 patients (4.0%; 95% confidence interval, 2.1%-5.9%) experienced major
      hemorrhage during UFH treatment, which in most patients occurred at the end of
      planned heparin therapy; one of the hemorrhages was fatal. Six patients (1.4%;
      95% confidence interval, 0.3%-2.5%) developed clinically suspected recurrent
      venous thromboembolism (fatal in 1 case) during UFH treatment or within 7 days'
      cessation. CONCLUSIONS: Administration of continuous intravenous UFH in patients
      with DVT or PE in routine clinical practice leads to a major bleeding rate of
      4.0%. This rate is comparable to the rate of major bleeding in patients who
      received UFH in clinical trials. Our findings are relevant to the discussion of
      major bleeding rates in patients with DVT and PE treated in daily clinical
      practice with subcutaneous low-molecular-weight heparin and newer antithrombotic
      drugs.

PMID- 10927737
TI  - Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking.
AB  - BACKGROUND: Legumes have reported benefits in terms of reduced risk for coronary
      heart disease and of colonic health. A novel legume fiber, cocoa bran, also may
      have favorable health effects on serum lipid levels, low-density lipoprotein
      (LDL) cholesterol oxidation, and fecal bulk. METHODS: Twenty-five healthy
      normolipidemic subjects (13 men and 12 women) (mean +/- SEM age, 37 +/- 2 years;
      mean +/- SEM body mass index [calculated as weight in kilograms divided by the
      square of height in meters], 24.6 +/- 0.7) ate cocoa-bran and chocolate-flavored
      low-fiber breakfast cereals for 2-week periods, with 2-week washout, in a double
      blind crossover study. The cocoa-bran cereal provided 25.0 g/d of total dietary
      fiber (TDF). The low-fiber cereal (5.6 g/d TDF) was of similar appearance and
      energy value. Fasting blood samples were obtained at the start and end of each
      period, and 4-day fecal collections were made from days 11 through 14. RESULTS:
      High-density lipoprotein (HDL) cholesterol level was higher (7.6% +/- 2.9%; P
      =.02) and the LDL/HDL cholesterol ratio was lower (6.7% +/- 2.3%; P =.007) for
      cocoa-bran compared with low-fiber cereal at 2 weeks. No effect was seen on LDL
      cholesterol oxidation. Mean fecal output was significantly higher for cocoa-bran
      than for low-fiber cereal (56 +/- 14 g/d; P<.001) and equal to the increase seen
      in the same subjects with wheat fiber in a previous study. CONCLUSIONS: A
      chocolate-flavored cocoa-bran cereal increased fecal bulk similarly to wheat bran
      and was associated with a reduction in the LDL/HDL cholesterol ratio. In view of
      the low-fat, high-fiber nature of the material, these results suggest a possible
      role for this novel fiber source in the diets of normal, hyperlipidemic, and
      constipated subjects.

PMID- 10927738
TI  - Where's the beef? The role of cross-contamination in 4 chain restaurant
      associated outbreaks of Escherichia coli O157:H7 in the Pacific Northwest.
AB  - BACKGROUND: From March through August 1993, outbreaks of Escherichia coli O157:H7
      occurred at 4 separate Oregon and Washington steak and salad bar restaurants
      affiliated with a single national chain. OBJECTIVE: To determine the cause of
      outbreaks of E coli O157:H7 at 4 chain restaurants. METHODS: Independent case
      control studies were performed for each outbreak. Available E coli O157:H7
      isolates were subtyped by pulse-field gel electrophoresis and by phage typing.
      RESULTS: Infection was not associated with beef consumption at any of the
      restaurants. Implicated foods varied by restaurant but all were items served at
      the salad bar. Among the salad bar items, no single item was implicated in all
      outbreaks, and no single item seemed to explain most of the cases at any
      individual restaurant. Molecular subtyping of bacterial isolates indicated that
      the first 2 outbreaks, which occurred concurrently, were caused by the same
      strain, the third outbreak was caused by a unique strain, and the fourth was
      multiclonal. CONCLUSIONS: Independent events of cross-contamination from beef
      within the restaurant kitchens, where meats and multiple salad bar items were
      prepared, were the likely cause of these outbreaks. Meat can be a source of E
      coli O157:H7 infection even if it is later cooked properly, underscoring the need
      for meticulous food handling at all stages of preparation.

PMID- 10927739
TI  - Report of a false-positive HIV test result and the potential use of additional
      tests in establishing HIV serostatus.
AB  - Considering the lifelong implications of a positive human immunodeficiency virus
      (HIV) test result, physicians should be aware of the limitations of tests for
      HIV. A 43-year-old man had a reactive enzyme-linked immunosorbent assay and an
      indeterminate result on Western blot analysis. The results of subsequent enzyme
      linked immunosorbent assay and Western blot tests were interpreted as positive,
      and the patient was informed that he had HIV infection. Persistently undetectable
      plasma HIV-1 RNA, combined with normal physical examination findings, CD4(+) cell
      count, and CD4/CD8 ratio, prompted further testing, which revealed that the
      patient was not infected with HIV. False-positive HIV test results are uncommon,
      but they can occur. In the appropriate clinical setting, follow-up and the use of
      other laboratory tests, such as determination of plasma viral load, may help
      identify such cases.

PMID- 10927740
TI  - Prenatal cocaine exposure and the expanding spectrum of brain malformations.

PMID- 10927741
TI  - Pyoderma gangrenosum induced by acupuncture in a patient with ulcerative colitis.

PMID- 10927742
TI  - Hypertensive crisis following meperidine administration and chemoembolization of
      a carcinoid tumor.

PMID- 10927743
TI  - An immunologic mechanism for the association between obesity and asthma.

PMID- 10927744
TI  - More research needed on the association between diagonal earlobe crease and
      coronary artery disease.

PMID- 10927746
TI  - Tea is good for the heart.

PMID- 10927747
TI  - Pericardial effusion in acquired immunodeficiency disease.

PMID- 10927749
TI  - Tobacco use and chronic fatigue syndrome, fibromyalgia, and temporomandibular
      disorder.

PMID- 10927751
TI  - The use of practitioner education and a warfarin monitoring service to improve
      anticoagulation practices.

PMID- 10927752
TI  - Geriatric assessment and anticoagulation in elderly patients with chronic atrial
      fibrillation.

PMID- 10927753
TI  - Warfarin therapy for atrial fibrillation: the patient's preference is important.

PMID- 10927756
TI  - JAMA 100 years ago: the right of property in medical records

PMID- 10927755
TI  - JAMA 100 years ago: power to regulate sale of cigarettes

PMID- 10927758
TI  - Debating pros and cons of stem cell research.

PMID- 10927757
TI  - JAMA 100 years ago: To what dying declarations must relate

PMID- 10927759
TI  - Vaccine aimed at African HIV to begin trials.

PMID- 10927761
TI  - The world in medicine: ECG limitations

PMID- 10927760
TI  - Calling the shots: IOM report calls for immunization revisions. Institute of
      Medicine.

PMID- 10927762
TI  - The world in medicine: AIDS care in the americas

PMID- 10927763
TI  - The world in medicine: adult asthma rising

PMID- 10927764
TI  - The world in medicine: alcohol deaths in sweden

PMID- 10927765
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927766
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927767
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927768
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927769
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927770
TI  - Estrogen-progestin replacement and risk of breast cancer.

PMID- 10927771
TI  - Methadone maintenance for opioid dependence.

PMID- 10927772
TI  - Methadone maintenance for opioid dependence.

PMID- 10927773
TI  - Methadone maintenance for opioid dependence

PMID- 10927774
TI  - Serologic testing for Lyme disease.

PMID- 10927775
TI  - Serologic testing for lyme disease

PMID- 10927776
TI  - Investment of health insurers and mutual funds in tobacco stocks.

PMID- 10927777
TI  - US college students' use of tobacco products: results of a national survey.
AB  - CONTEXT: Adults aged 18 to 24 years, many of whom are in college, represent the
      youngest legal targets for tobacco industry marketing. Cigarette smoking has been
      described among college students, but little is known about non-cigarette tobacco
      use by college students or cigar use by adults of any age. OBJECTIVES: To assess
      the prevalence of all forms of tobacco use (cigarettes, cigars, pipes, and
      smokeless tobacco) among US college students and to identify student- and college
      level factors associated with use of each product. DESIGN: The Harvard College
      Alcohol Survey, a self-administered survey conducted in 1999. SETTING: One
      hundred nineteen nationally representative US 4-year colleges. SUBJECTS: A total
      of 14,138 randomly selected students (60% response rate). MAIN OUTCOME MEASURES:
      Self-report of current (in the past 30 days), past-year, and lifetime use of
      cigarettes, cigars, pipes, smokeless tobacco, and all tobacco products. RESULTS:
      Nearly half (45.7%) of respondents had used a tobacco product in the past year
      and one third (32.9%) currently used tobacco. Cigarettes accounted for most of
      the tobacco use (28.5% current prevalence), but cigar use was also substantial
      (37.1% lifetime prevalence, 23.0% past-year prevalence, and 8.5% current
      prevalence) and combinations of the 2 were common. Total tobacco use was higher
      in men than in women (37. 9% vs 29.7%; P<.001), despite nearly identical current
      cigarette smoking rates between the sexes (28.5% for women vs 28.4% for men),
      because of greater use of cigars (current prevalence, 15.7% vs 3.9%; P<.001) and
      smokeless tobacco (current prevalence, 8.7% vs 0.4%; P<. 001) by men. Tobacco use
      was significantly higher among white students (P<.001), users of other substances
      (alcohol and marijuana) (P<.001), and students whose priorities were social
      rather than educational or athletic (P<.05). Among students who had used both
      cigars and cigarettes, only 8.9% smoked cigars at an earlier age than they had
      smoked cigarettes. CONCLUSION: Our study indicates that tobacco use is common
      among college students and is not limited to cigarettes. College appears to be a
      time when many students are trying a range of tobacco products and are in danger
      of developing lifelong nicotine dependence. National efforts to monitor and
      reduce tobacco use of all types should expand to focus on college students and
      other young adults. JAMA. 2000;284:699-705

PMID- 10927778
TI  - Smoking vs other risk factors as the cause of smoking-attributable deaths:
      confounding in the courtroom.
AB  - CONTEXT: The surgeon general estimates that more than 400,000 deaths are
      attributable to smoking annually in the United States. The tobacco industry has
      criticized the surgeon general's estimates because they do not control for the
      lower educational and socioeconomic status of modern-day smokers. OBJECTIVE: To
      determine whether controlling for education, occupation, race, alcohol
      consumption, and various dietary factors, in addition to age and sex,
      substantially alters the relative and attributable risk estimates associated with
      tobacco smoking. DESIGN, SETTING, AND PARTICIPANTS: Nationwide American Cancer
      Society prospective cohort study of 974, 150 US adults aged 30 years or older,
      enrolled in 1982 and followed up through 1988. (The same study is used for the
      surgeon general and Centers for Disease Control and Prevention [CDC] estimates of
      smoking-attributable deaths in the United States.) MAIN OUTCOME MEASURES: Death
      from each of the chronic diseases considered in the CDC's estimate of smoking
      attributable mortality (cancers of the lung, oropharynx, larynx, esophagus,
      pancreas, kidney, bladder, and cervix; ischemic heart disease, arterial disease,
      and other heart conditions; stroke; chronic obstructive pulmonary disease; and
      other respiratory conditions). Estimates adjusted for multiple covariates were
      compared with those adjusted for age only among current and former vs never
      smokers. RESULTS: Adjusting for multiple covariates slightly decreased the
      relative and attributable risk estimates for current smoking in both men and
      women, but slightly increased the estimates for former smoking in women.
      Multivariate adjustment decreased the overall estimate of deaths attributable to
      smoking in the United States by approximately 1%, from 401,109 to 396,741 per
      year. CONCLUSIONS: Our study suggests that federal estimates of deaths caused by
      smoking are not substantially altered by adjustment for behavioral and
      demographic factors associated with smoking beyond the current adjustment for age
      and sex. JAMA. 2000;284:706-712

PMID- 10927779
TI  - Smoking cessation and risk of age-related cataract in men.
AB  - CONTEXT: Although cigarette smoking has been shown to be a risk factor for age
      related cataract, data are inconclusive on the risk of cataract in individuals
      who quit smoking. OBJECTIVE: To examine the association between smoking cessation
      and incidence of age-related cataract. DESIGN: Prospective cohort study conducted
      from 1982 through 1997, with an average follow-up of 13.6 years. SETTING AND
      PARTICIPANTS: A total of 20,907 US male physicians participating in the
      Physicians' Health Study I who did not have a diagnosis of age-related cataract
      at baseline and had reported their level of smoking at baseline. MAIN OUTCOME
      MEASURES: Incident age-related cataract defined as self-report confirmed by
      medical record review, diagnosed after study randomization and responsible for
      vision loss to 20/30 or worse, and surgical extraction of incident age-related
      cataract, in relation to smoking status and years since quitting smoking.
      RESULTS: At baseline, 11% were current smokers, 39% were past smokers, and 50%
      were never smokers. Average reported cumulative dose of smoking at baseline was
      approximately 2-fold greater in current than in past smokers (35.8 vs 20.5 pack
      years). Two thousand seventy-four incident cases of age-related cataract and 1193
      cataract extractions were confirmed during follow-up. Compared with current
      smokers, multivariate relative risks (RRs) of cataract in past smokers who quit
      smoking fewer than 10 years, 10 to fewer than 20 years, and 20 or more years
      before the study were 0.79 (95% confidence interval [CI], 0.64-0.98), 0.73 (95%
      CI, 0.61-0.88), and 0.74 (95% CI, 0.63-0.87), respectively, after adjustment for
      other risk factors for cataract and age at smoking inception. The RR for never
      smokers was 0.64 (95% CI, 0.54-0.76). The reduced risk in past smokers was
      principally due to a lower total cumulative dose (RR of cataract for increase of
      10 pack-years of smoking, 1.07; 95% CI, 1.04-1.10). A benefit of stopping smoking
      independent of cumulative dose was suggested in some analyses. Results for
      cataract extraction were similar. CONCLUSION: These prospective data indicate
      that while some smoking-related damage to the lens may be reversible, smoking
      cessation reduces the risk of cataract primarily by limiting total dose-related
      damage to the lens. JAMA. 2000;284:713-716

PMID- 10927780
TI  - Association between household and workplace smoking restrictions and adolescent
      smoking.
AB  - CONTEXT: Recent marked increases in adolescent smoking indicate a need for new
      prevention approaches. Whether workplace and home smoking restrictions play a
      role in such prevention is unknown. OBJECTIVE: To assess the association between
      workplace and home smoking restrictions and adolescent smoking. DESIGN, SETTING,
      AND SUBJECTS: Data were analyzed from 2 large national population-based surveys,
      the Current Population Surveys of 1992-1993 and 1995-1996, which included 17,185
      adolescents aged 15 to 17 years. MAIN OUTCOME MEASURES: Smoking status of the
      adolescents surveyed, compared by presence of home and workplace smoking
      restrictions. RESULTS: After adjusting for demographics and other smokers in the
      household, adolescents who lived in smoke-free households were 74% (95%
      confidence interval [CI], 62%-88%) as likely to be smokers as adolescents who
      lived in households with no smoking restrictions. Similarly, adolescents who
      worked in smoke-free workplaces were 68% (95% CI, 51%-90%) as likely to be
      smokers as adolescents who worked in a workplace with no smoking restrictions.
      Adolescent smokers were 1.80 (95% CI, 1.23-2.65) times more likely to be former
      smokers if they lived in smoke-free homes. The most marked relationship of home
      smoking restrictions to current adolescent smoking occurred in households where
      all other members were never-smokers. Current smoking prevalence among
      adolescents in homes without smoking restrictions approached that among
      adolescents in homes with a current smoker but with smoking restrictions.
      CONCLUSIONS: Parents with minor children should be encouraged to adopt smoke-free
      homes. Smoke-free workplaces can also augment smoking prevention. These findings
      emphasize the importance of tobacco control strategies aimed at the entire
      population rather than at youth alone. JAMA. 2000;284:717-722

PMID- 10927781
TI  - Changes in youth cigarette use and intentions following implementation of a
      tobacco control program: findings from the Florida Youth Tobacco Survey, 1998
      2000.
AB  - CONTEXT: Many states are developing tobacco use prevention and reduction
      programs, and current data on tobacco use behaviors and how these change over
      time in response to program activities are needed for program design,
      implementation, and evaluation. OBJECTIVES: To assess changes in youth cigarette
      use and intentions following implementation of the Florida Pilot Program on
      Tobacco Control. DESIGN, SETTING, AND PARTICIPANTS: Self-administered survey
      conducted prior to program implementation (1998), and 1 and 2 years (1999, 2000)
      later among a sample of Florida public middle school and high school students who
      were classified as never users, experimenters, current users, and former users of
      cigarettes based on survey responses. MAIN OUTCOME MEASURES: Changes in cigarette
      use status, intentions, and behaviors among students over a 2-year period.
      RESULTS: Surveys were completed by 22,540, 20,978, and 23, 745 students attending
      255, 242, and 243 Florida public middle and high schools in 1998, 1999 and 2000,
      respectively. Response rates for the 3 survey years ranged from 80% to 82% and
      72% to 82% for the middle school and high school surveys, respectively. After 2
      years, current cigarette use dropped from 18.5% to 11.1% (P<.001) among middle
      school students and from 27.4% to 22.6% (P =.01) among high school students.
      Prevalence of never use increased from 56.4% to 69. 3% (P<.001) and from 31.9% to
      43.1% (P =.001) among middle school and high school students, respectively.
      Prevalence of experimenting decreased among middle school and high school
      students from 21.4% to 16.2% (P<.001) and from 32.8% to 28.2% (P<.001),
      respectively. Among never users, the percentage of committed nonsmokers increased
      from 67.4% to 76.9% (P<.001) and from 73.7% to 79.3% (P<.001) among middle school
      and high school students, respectively. Among experimenters, the percentage of
      students who said they will not smoke again increased from 30.4% to 42.0%
      (P<.001) in middle school and from 44.4% to 51.0% (P<.001) in high school.
      CONCLUSIONS: Progress toward reduction of youth tobacco use was observed in each
      of the 2 years of Florida's Pilot Program on Tobacco Control. Our results suggest
      that a comprehensive statewide program can be effective in preventing and
      reducing youth tobacco use. JAMA. 2000;284:723-728

PMID- 10927782
TI  - Factors associated with tobacco sales to minors: lessons learned from the FDA
      compliance checks.
AB  - CONTEXT: Tobacco products continue to be widely accessible to minors. Between
      1997 and 1999, the US Food and Drug Administration (FDA) conducted more than
      150,000 tobacco sales age-restriction compliance checks. Data obtained from these
      checks provide important guidance for curbing illegal sales. OBJECTIVE: To
      determine which elements of the compliance checks were most highly associated
      with illegal sales and thereby inform best practices for conducting efficient
      compliance check programs. DESIGN AND SETTING: Cross-sectional analysis of FDA
      compliance checks in 110,062 unique establishments in 36 US states and the
      District of Columbia. MAIN OUTCOME MEASURE: Illegal sales of tobacco to minors at
      compliance checks; association of illegal sales with variables such as age and
      sex of the minor. RESULTS: The rate of illegal sales for all first compliance
      checks in unique stores was 26.6%. Clerk failure to request proof of age was
      strongly associated with illegal sales (uncorrected sales rate, 10.5% compared
      with 89.5% sales when proof was not requested; multivariate-adjusted odds ratio
      [OR], 0.03; 95% confidence interval [CI], 0.03-0.04). Other factors associated
      with increased illegal sales were employment of older minors to make the purchase
      attempt (adjusted ORs for 16- and 17-year-old minors compared with 15-year-olds
      were 1.52 [95% CI, 1.46-1.63] and 2.43 [95% CI, 2.31-2. 59], respectively),
      attempt to purchase smokeless tobacco (adjusted OR, 2.16 [95% CI, 1.90-2.45] vs
      cigarette purchase attempts), and performing checks at or after 5 PM (adjusted
      OR, 1.28 [95% CI, 1. 21-1.35] vs before 5 PM). Female sex of clerk and minor,
      Saturday checks, type of store (convenience store selling gas, gas station,
      drugstore, supermarket and general merchandise), and rural store locations also
      were associated with increased illegal sales. CONCLUSIONS: This analysis found
      that a request for age verification strongly predicted compliance with the law.
      The results suggest several ways in which the process of compliance checks might
      be optimized. JAMA. 2000;284:729-734

PMID- 10927783
TI  - Health risks associated with cigar smoking.
AB  - This article summarizes principal findings from a conference convened by the
      American Cancer Society in June 1998 to examine the health risks of cigar
      smoking. State-of-the-science reports were presented and 120 attendees
      (representing government and private agencies, academia, health educators, and
      tobacco control experts) participated in panels and summary development
      discussions. The following conclusions were reached by consensus: (1) rates of
      cigar smoking are rising among both adults and adolescents; (2) smoking cigars
      instead of cigarettes does not reduce the risk of nicotine addiction; (3) as the
      number of cigars smoked and the amount of smoke inhaled increases, the risk of
      death related to cigar smoking approaches that of cigarette smoking; (4) cigar
      smoke contains higher concentrations of toxic and carcinogenic compounds than
      cigarettes and is a major source of fine-particle and carbon monoxide indoor air
      pollution; and (5) cigar smoking is known to cause cancers of the lung and upper
      aerodigestive tract. JAMA. 2000;284:735-740

PMID- 10927784
TI  - A 36-year-old woman who smokes cigarettes.

PMID- 10927786
TI  - Achieving worldwide tobacco control.

PMID- 10927785
TI  - A 36-year-old woman with endometriosis, pelvic pain, and infertility, 1 year
      later.

PMID- 10927787
TI  - Tobacco control in the 21st century: searching for answers in a sea of change.

PMID- 10927788
TI  - Environmental tobacco smoke exposure among police officers in Hong Kong.
AB  - CONTEXT: Few epidemiological studies have examined the relationship between
      chronic respiratory symptoms and exposure to environmental tobacco smoke (ETS) at
      work in adults, and none have shown clear dose-response relationships. OBJECTIVE:
      To examine the respiratory effects of ETS exposure at home and at work among
      never-smoking adults. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional, self
      administered questionnaire survey conducted in December 1995 and January 1996
      among 4468 male and 728 female police officers in Hong Kong who were never
      smokers. MAIN OUTCOME MEASURES: Respiratory symptoms and physician consultation
      in the previous 14 days for such symptoms by presence and amount of ETS exposure
      at work. RESULTS: Eighty percent of both men and women reported ETS exposure at
      work. Significant odds ratios (ORs) for respiratory symptoms were found among men
      with ETS exposure at work (for any respiratory symptoms, difference in absolute
      rate, 20.4%; OR, 2.33; 95% confidence interval [CI], 1.97-2.75; attributable
      risk, 57%) and physician consultation (difference in absolute rate, 4.5%; OR,
      1.30; 95% CI, 1. 05-1.61; attributable risk, 23%). Trends were similar among
      women for any respiratory symptoms (difference in absolute rate, 15.4%; OR, 1.63;
      95% CI, 1.04-2.56; attributable risk, 39%) and for physician consultation
      (difference in absolute rates, 2.8%; OR, 1.45; 95% CI, 0.87-2.41; attributable
      risk, 31%). Positive dose-response relationships with number of coworkers smoking
      nearby and amount of ETS exposure in the work place were found. CONCLUSIONS: This
      study provides further evidence of the serious health hazards associated with ETS
      exposure at work. The findings support a ban on smoking in the workplace to
      protect all workers in both developed and developing countries. JAMA.
      2000;284:756-763

PMID- 10927789
TI  - Two expanded repeats in the same patient: An effect on phenotype?

PMID- 10927790
TI  - Lice, fleas, and strokes.

PMID- 10927791
TI  - Surgery for Parkinson disease: A critical evaluation of the state of the art.

PMID- 10927792
TI  - Applicability of yeast genetics to neurologic disease.
AB  - As advances in gene mapping technology reveal genes associated with neurologic
      diseases, the need to identify a gene's normal function arises often.
      Experimental genetics is very useful in identifying a gene's function. It relies
      on model organisms both because it is not appropriate in humans, and because many
      processes are remarkably similar among eukaryotes. Many cellular processes have
      evolved once, and species differences are variations on a theme. Molecular
      genetic tools available in the yeast Saccharomyces cerevisiae provide a means to
      more rapidly reach an understanding of gene function, yielding substantial
      insight into the same process in humans. Yeast will never complain of headache or
      "spells," but do have expansions of trinucleotide repeats, prions, and other
      processes very much analogous to those underlying many neurologic diseases. In
      spite of the absence of a nervous system in yeast, yeast genetics has contributed
      substantial insight into neurologic diseases mechanisms. The real strength of
      yeast in studying human disease is in genetic analysis of gene function and in
      providing genetically powerful functional assays. Arch Neurol. 2000;57:1129-1134

PMID- 10927793
TI  - Coexisting causes of ischemic stroke.
AB  - BACKGROUND: Coexistence of multiple potential causes of cerebral infarct (MPCI)
      has been poorly studied. OBJECTIVE: To determine the risk factors, clinical
      findings, and topographical patterns of patients with at least 2 potential causes
      of cerebral infarct. DESIGN: Data analysis from a prospective acute stroke
      registry (the Lausanne Stroke Registry, Lausanne, Switzerland) in a community
      based primary care center. RESULTS: Among 3525 patients with first-ever ischemic
      stroke consecutively admitted to a primary care stroke center, 250 patients (7%)
      had at least 2 MPCIs, with the following subgroups: large artery disease and a
      cardiac source of embolism (LAD + CSE) (43%), small artery disease and CSE (SAD +
      CSE) (34%), LAD + SAD (18%), and LAD + SAD + CSE (5%). Hypertension, cardiac
      ischemia, and a history of atrial fibrillation predominated in the LAD + SAD +
      CSE subgroup (P<.001), while cigarette smoking was more prevalent in the LAD +
      SAD subgroup (P<.05). A decreased level of consciousness and speech disorders
      were more common in the LAD + CSE subgroup (P<.001). Lacunar syndromes
      predominated in the LAD + SAD subgroup. Pure motor stroke was the most frequent
      lacunar syndrome in all subgroups, but sensory motor stroke predominated in the
      LAD + CSE subgroup (P<.05). The outcome at 1 month was worse in the LAD + CSE and
      SAD + CSE subgroups (P<.001). Other stroke characteristics and clinical features
      did not differ significantly between the 4 subgroups of patients with MPCI.
      CONCLUSIONS: Our findings suggest that MPCIs are uncommon. The most frequent
      association is LAD + CSE. Topographical patterns of stroke and clinical
      characteristics in patients with MPCI only rarely allow emphasis of a preeminent
      cause. Arch Neurol. 2000;57:1139-1144

PMID- 10927794
TI  - Contribution of Lewy body inclusions to dementia in patients with and without
      Alzheimer disease neuropathological conditions.
AB  - CONTEXT: Lewy bodies (LBs) are intraneuronal inclusions in the brain that have
      been increasingly recognized as neuropathological lesions with relevance not only
      to Parkinson disease but also to Alzheimer disease. However, the degree to which
      the density of LBs in the brain contributes to the severity of dementia has not
      been clear. OBJECTIVE: To determine the degree to which LB "burden" contributes
      to dementia. DESIGN: Brain specimens were examined from 273 consecutive autopsies
      of elderly subjects residing in a nursing home. The numbers and densities of LBs
      were determined in multiple brain regions, and their correlation with a measure
      of cognition and functional status (Clinical Dementia Rating) during the 6 months
      preceding death was determined. SETTING AND PATIENTS: Postmortem study of nursing
      home residents. RESULTS: The severity of dementia correlated significantly and
      positively with the density of LBs. These correlations were independent of other
      neuropathological disorders commonly associated with dementia, including
      Alzheimer disease. The density of LBs correlated significantly with dementia
      severity whether or not the diagnostic criteria for Alzheimer disease were met
      and after the contribution of classical Alzheimer disease lesions, neuritic
      plaques, and neurofibrillary tangles had been accounted for by partial
      correlation analysis. CONCLUSION: Lewy body inclusions appear to contribute
      significantly to cognitive deficits in the elderly in a manner that is
      independent of other neuropathological disorders. Arch Neurol. 2000;57:1145-1150

PMID- 10927795
TI  - Cytokine gene expression as a function of the clinical progression of Alzheimer
      disease dementia.
AB  - BACKGROUND: Inflammatory cytokines have been linked to Alzheimer disease (AD)
      neurodegeneration, but little is known about the temporal control of their
      expression in relationship to clinical measurements of AD dementia progression.
      DESIGN AND MAIN OUTCOME MEASURES: We measured inflammatory cytokine messenger RNA
      (mRNA) expression in postmortem brain specimens of elderly subjects at different
      clinical stages of dementia and neuropathological dysfunction. SETTING AND
      PATIENTS: Postmortem study of nursing home patients. RESULTS: In brains of
      cognitively normal control subjects, higher interleukin 6 (IL-6) and transforming
      growth factor beta1 (TGF-beta1) mRNA expression was observed in the entorhinal
      cortex and superior temporal gyrus compared with the occipital cortex. Compared
      with age-matched controls, subjects with severe/terminal dementia, but not
      subjects at earlier disease stages, had higher IL-6 and TGF-beta1 mRNA expression
      in the entorhinal cortex (P<.01) and superior temporal gyrus (P<.01). When
      stratified by the Consortium to Establish a Registry for Alzheimer's Disease
      (CERAD) neuropathological criteria, IL-6 mRNA expression in both the entorhinal
      cortex (P<.05) and superior temporal gyrus (P<.01) correlated with the level of
      neurofibrillary tangles but not neuritic plaques. However, in the entorhinal
      cortex, TGF-beta1 mRNA did not correlate with the level of either neurofibrillary
      tangles or neuritic plaques. Interestingly, in the superior temporal gyrus, TGF
      beta1 mRNA expression negatively correlated with neurofibrillary tangles (P<.01)
      and showed no relationship to the pathological features of neuritic plaques.
      CONCLUSIONS: The data are consistent with the hypothesis that cytokine expression
      may differentially contribute to the vulnerability of independent cortical
      regions during the clinical progression of AD and suggest that an inflammatory
      cytokine response to the pathological effects of AD does not occur until the late
      stages of the disease. These findings have implications for the design of anti
      inflammatory treatment strategies. Arch Neurol. 2000;57:1153-1160

PMID- 10927796
TI  - Hemodynamic assessment of acute stroke using dynamic single-slice computed
      tomographic perfusion imaging.
AB  - BACKGROUND: Stroke management would benefit from a broadly available imaging tool
      that detects perfusion deficits in patients with acute stroke. OBJECTIVE: To
      determine the role of dynamic, single-slice computed tomographic (CT) perfusion
      imaging (CTP) in the assessment of acute middle cerebral artery stroke. DESIGN
      AND PATIENTS: Imaging with CTP and CT within the first 6 hours of symptom onset
      and before the start of treatment in a consecutive clinical series of 22 patients
      (mean age, 68.3 years; 14 women; studied within 143 +/- 96 minutes of stroke
      onset). SETTING: A stroke unit in a university hospital. MAIN OUTCOME MEASURES:
      Area of the perfusion deficit (nAP(0)) from time-to-peak maps, hemispheric lesion
      area from follow-up CT (HLA(F)), final infarct volume, and stroke recovery
      (National Institutes of Health Stroke Scale scores). RESULTS: Eighteen patients
      had perfusion deficits in the middle cerebral artery territory and corresponding
      hypoattenuation in follow-up CT. Three patients with normal CTP findings showed
      lacunar infarctions or normal findings on follow-up CT. In 1 patient, CTP did not
      reveal a territorial deficit above the imaging slice. The overall sensitivity and
      specificity of CTP for the detection of perfusion deficits in patients with
      proven territorial infarction (n = 18) on follow-up CT were 95% and 100%,
      respectively. The nAP(0) was significantly correlated with the National
      Institutes of Health Stroke Scale score at admission (P<.003) and the HLA(F)
      (P<.001). Different stroke patterns were identified in patients with follow-up
      CTP (n = 10): (1) initial perfusion deficit and partial nutritional reperfusion
      (nAP(0)>HLA(F); n = 6), (2) initial perfusion deficit and nonnutritional
      reperfusion (nAP( 0)>/=HLA(F); n = 2), and (3) initial perfusion deficit without
      reperfusion (nAP(0)>/=HLA(F); n = 2). CONCLUSIONS: Computed tomographic perfusion
      imaging detects major perfusion deficits in the middle cerebral artery territory.
      Because CTP is broadly available, it may play a role in acute stroke management.
      Arch Neurol. 2000;57:1161-1166

PMID- 10927797
TI  - Clinical features of amyotrophic lateral sclerosis according to the El Escorial
      and Airlie House diagnostic criteria: A population-based study.
AB  - BACKGROUND: The El Escorial and the revised Airlie House diagnostic criteria for
      amyotrophic lateral sclerosis (ALS) classify patients into categories reflecting
      different levels of diagnostic certainty. We conducted a prospective, population
      based study of the natural course of ALS in the Republic of Ireland during a 6
      year period to examine the utility of these ALS diagnostic criteria. METHODS:
      Using data from the Irish ALS Register, we studied the clinical features of all
      patients diagnosed as having ALS in Ireland throughout their illness. RESULTS:
      Between 1993 and 1998, 388 patients were diagnosed as having ALS. Forty percent
      of patients reported bulbar-onset symptoms. Disease progression occurred over
      time: at last follow-up, 75% of all patients had bulbar signs, compared with 59%
      at diagnosis. When the El Escorial criteria were applied, more than half of
      patients (218 [56%]) had definite or probable ALS at diagnosis. Of the 165
      possible and suspected ALS cases at diagnosis (trial ineligible), 110 (67%) were
      trial eligible at last follow-up. Of the 254 patients who had died, 229 (90%) had
      definite or probable ALS, whereas 25 patients (10%) remained trial ineligible at
      death. El Escorial category at diagnosis was not a significant prognostic
      indicator. Use of the Airlie House criteria had no effect on the median time from
      symptom onset to trial eligibility (12.9 vs 12.8 months). CONCLUSIONS: The El
      Escorial and Airlie House diagnostic criteria are excessively restrictive.
      Furthermore, levels of diagnostic certainty cannot be used as prognostic
      indicators. Arch Neurol. 2000;57:1171-1176

PMID- 10927798
TI  - Beta-endorphin concentrations in peripheral blood mononuclear cells of patients
      with multiple sclerosis: effects of treatment with interferon beta.
AB  - CONTEXT: It has been reported that the opioid peptide beta-endorphin (BE) has
      immunosuppressive effects. Interferon beta (IFN-beta) is a well-established
      therapy for multiple sclerosis (MS), but immunological mechanisms underlying its
      beneficial effects in MS are partially undefined. OBJECTIVES: To determine BE
      levels in peripheral blood mononuclear cells (PBMCs) of patients with relapsing
      remitting MS during different phases of disease activity and the possible
      modulating effects of IFN-beta treatment on PBMC BE synthesis in patients with
      MS. DESIGN: We measured BE levels in blood samples collected from 6 patients with
      MS who had not experienced clinical changes during the previous 3 months
      (patients with stable MS) and from 7 patients with MS during a clinical relapse.
      We also surveyed BE levels in PBMC samples from 8 patients with MS before
      treatment and for 6 months after the beginning of IFN-beta administration. The
      control group was 13 healthy subjects. RESULTS: Low PBMC BE levels were detected
      in patients with stable MS and in those entering IFN-beta treatment compared with
      control subjects. Increased BE concentrations were observed in MS patients
      experiencing a clinical relapse compared with patients with stable MS. During IFN
      beta treatment, the levels of BE in PBMC samples from patients with MS increased
      significantly (after 1 month, P =.02; after 3 months, P =.007; and after 6
      months, P =.16). CONCLUSIONS: A reduction of BE levels was present in patients
      with clinically inactive MS. Treatment with IFN-beta seems to induce an increase
      of this opioid in PBMCs of MS patients. The increase of BE concentration during a
      clinical relapse may represent a possible control mechanism aimed at
      counterbalancing the inflammatory phase of the disease. Arch Neurol. 2000;57:1178
      1181

PMID- 10927799
TI  - Changes in activated T cells in the blood correlate with disease activity in
      multiple sclerosis.
AB  - OBJECTIVE: To determine whether changes in activation markers on peripheral blood
      T cells correlate with disease activity in patients with multiple sclerosis.
      DESIGN: In a prospective longitudinal study during 1 year, we analyzed the change
      in percentage of activated T lymphocytes in the peripheral blood of 40 patients
      with multiple sclerosis in relation to clinical findings and changes on brain
      magnetic resonance imaging (MRI) scans. The patients underwent repeated imaging
      of the brain (mean number of MRIs for each patient, 22) at the time blood samples
      were obtained as well as at monthly neurological examinations, and at the time of
      scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and ambulation
      index scale. RESULTS: A change in the percentage of cells expressing the
      activation markers interleukin 2 receptor (CD25), class II major
      histocompatibility complex (MHC) (I3) or surface dipeptidyl peptidase (CD26)
      correlated significantly with a change in lesion volume or a change in number of
      gadolinium-enhancing lesions as detected on MRI. Changes in CD25( +) cells and in
      CD4(+) cells expressing class II MHC also correlated with changes in disability
      as measured by EDSS in patients with relapsing-remitting disease, and changes in
      CD4(+)CD25(+) cells correlated with the occurrence of attacks in patients with
      relapsing-remitting disease. These correlations are dependent on measurement of
      changes between time points sampled at 1- or 2-week intervals. CONCLUSION: There
      is a linkage between peripheral T-lymphocyte activation as measured by cell
      surface markers and disease activity in patients with multiple sclerosis. Arch
      Neurol. 2000;57:1183-1189

PMID- 10927800
TI  - Botulinum toxin in the treatment of tics.
AB  - OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin A (BTX)
      injections in the treatment of tics in patients with Tourette syndrome (TS).
      BACKGROUND: BTX is an effective treatment for an increasing number of conditions
      characterized by abnormal muscle contractions. BTX may improve not only the motor
      component of tics, but also premonitory sensations that precede tics. METHODS:
      Thirty-five patients (30 male, 5 female) were treated with BTX in the sites of
      their most problematic tics. Response to BTX was based on a 0 to 4 clinical
      rating scale (0, no improvement, to 4, marked improvement in both severity and
      function). Questionnaires were administered to evaluate patients' impressions of
      overall efficacy and degree of benefit with premonitory sensations. RESULTS: Mean
      duration of tics prior to initial injection was 15.3 years (range, 1-62 years)
      and mean duration of follow-up was 21.2 months (range, 1. 5-84 months). The mean
      peak effect response in 35 patients treated in 115 sessions was 2.8 (range, 0-4);
      the mean duration of benefit was 14.4 weeks (maximum, 45 weeks); and the mean
      latency to onset of benefit was 3.8 days (maximum, 10 days). Twenty-one (84%) of
      25 patients with premonitory sensations derived marked relief of these symptoms
      (mean benefit, 70.6%). Total mean dose was 502.1 U (range, 15-3550 U); mean
      number of visits, 3.3 (range, 1-16); and mean dose per visit, 119.9 U (range, 15
      273 U). Sites of injections were as follows: cervical or upper thoracic area
      (17), upper face (14), lower face (7), vocal cords (4), upper back and/or
      shoulder (3), scalp (1), forearm (1), leg (1) and rectus abdominis (1).
      Complications included neck weakness (4), dysphagia (2), ptosis (2), nausea (1),
      hypophonia (1), fatigue (1), and generalized weakness (1), which were all mild
      and transient. CONCLUSIONS: Botulinum toxin A injections are an effective and
      well-tolerated treatment of tics. In addition to improving the motor component of
      tics, BTX also provides relief of premonitory sensations. Arch Neurol.
      2000;57:1190-1193

PMID- 10927801
TI  - Clinical subtypes of essential tremor.
AB  - BACKGROUND: There is clinical variability in essential tremor (ET), but it is not
      clear whether this variability is because of the existence of distinct clinical
      subtypes of ET (ie, forms of ET that may differ in their etiology, rate of
      progression, or response to treatment). OBJECTIVES: To examine in a group of ET
      cases the age of onset, anatomic distribution, and rate of progression of tremor,
      and to look for associations between these factors. METHODS: Cases of ET were
      ascertained from a community (n = 60) and a tertiary referral clinic (n = 55) in
      northern Manhattan, New York, NY. All subjects underwent an interview and
      videotaped tremor examination. Rate of progression was estimated based on the
      tremor severity and reported disease duration at the time of evaluation. RESULTS:
      Age of onset was bimodally distributed in clinic cases. There were differences in
      the anatomic distribution of the tremor (arm tremor only vs head and arm tremor
      vs isolated head tremor). Rate of progression was distributed exponentially;
      there was a large cluster of subjects with slower rates of progression, and a
      smaller number who had faster rates. There was an association between age of
      onset and rate of progression (r = 0.46-0.50, P<.002); cases with older age of
      onset (>60 years) progressed more rapidly (P<.001). In addition, upper limb
      tremor progressed more slowly among those with concomitant head tremor (P =.03).
      CONCLUSIONS: Essential tremor is not a homogeneous condition. There are
      differences in age of onset, anatomic distribution of tremor, and rate of
      progression. The ET in several groups of patients in this study (those with age
      of onset >60 years and those without head tremor) progressed more rapidly,
      suggesting that these ET cases may define distinct clinical subtypes. These
      subtypes should be further assessed for etiologic and genetic heterogeneity as
      well as differences in responsiveness to therapeutic agents. Arch Neurol.
      2000;57:1194-1198

PMID- 10927802
TI  - A patient with 2 different repeat expansion mutations.
AB  - BACKGROUND: Many inherited progressive encephalopathies have a poor outcome, and
      some are caused by repeat expansion mutations. How would the presence of 2
      different expansion mutations affect the phenotype? OBJECTIVE: To describe a
      patient who has 2 distinct, rare genetic disorders: myotonic dystrophy (DM, OMIM
      160900) and progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1,
      OMIM 254800). Both conditions are caused by repeat expansion mutations. They
      affect the central nervous system causing mental retardation, but also produce a
      wide spectrum of disabilities in daily living. SETTING: Referral center. METHODS:
      Clinical description with accompanying photographs, electroencephalography and
      magnetic resonance imaging; DNA analysis of both of the mutations and chromosomal
      analysis with prometaphase spreads. RESULTS: The patient had clinical
      characteristics and findings of both myotonic dystrophy and progressive myoclonus
      epilepsy of the Unverricht-Lundborg type. Electroencephalographic recordings over
      a 3-year period showed typical findings for myoclonus epilepsy. The patient had
      no gross anomalies in brain magnetic resonance imaging. She had a normal
      karyotype, and both of the diagnoses were confirmed at the molecular level with
      the direct detection of the mutations. CONCLUSIONS: Despite having 2 different
      progressive inherited disorders affecting the central nervous system, the
      patient, at age 28 years, showed only mild mental retardation with very slow
      progression. However, clear deterioration in activities of daily living has taken
      place during last 3 years. Arch Neurol. 2000;57:1199-1203

PMID- 10927803
TI  - Acute aphasia in multiple sclerosis.
AB  - Acute aphasia is rare in multiple sclerosis. We describe 3 patients with multiple
      sclerosis who had acute exacerbations presenting as aphasias. One patient had a
      mixed transcortical aphasia, 1 had a transcortical motor aphasia, and 1 had a
      Broca aphasia. Magnetic resonance imaging scans of the brain with contrast
      enhancement revealed new white matter lesions in the left hemisphere in all 3
      patients. Two of the 3 patients had a good response to treatment with
      methylprednisolone sodium succinate. Arch Neurol. 2000;57:1207-1209

PMID- 10927804
TI  - A case of Balamuthia mandrillaris meningoencephalitis.
AB  - Balamuthia mandrillaris is a newly described pathogen that causes granulomatous
      amebic encephalitis, an extremely rare clinical entity that usually occurs in
      immunosuppressed individuals. We report a case of pathologically proven
      Balamuthia encephalitis with unusual laboratory and radiologic findings. A 52
      year-old woman with idiopathic seizures and a 2-year history of chronic
      neutropenia of unknown cause had a subacute illness with progressive lethargy,
      headaches, and coma and died 3 months after the onset of symptoms. Cerebrospinal
      fluid (CSF) glucose concentrations were extremely low or unmeasurable, a feature
      not previously described (to our knowledge). Cranial magnetic resonance imaging
      scans showed a single large temporal lobe nodule, followed 6 weeks later by the
      appearance of 18 ring-enhancing lesions in the cerebral hemispheres that
      disappeared after treatment with antibiotics and high-dose corticosteroids. The
      initial brain biopsy specimen and analysis of CSF samples did not demonstate
      amebae, but a second biopsy specimen and the postmortem pathologic examination
      showed Balamuthia trophozoites surrounded by widespread granulomatous
      inflammation and vasculitis. The patient's neutropenia and antibiotic use may
      have caused susceptibility to this organism. Amebic meningoencephalitis should be
      considered in cases of subacute meningoencephalitis with greatly depressed CSF
      glucose concentrations and multiple nodular lesions on cerebral imaging. Arch
      Neurol. 2000;57:1210-1212

PMID- 10927806
TI  - Resolution of migraine with aura caused by an occipital arteriovenous
      malformation.

PMID- 10927805
TI  - The brain lesion responsible for parkinsonism after carbon monoxide poisoning.
AB  - BACKGROUND: Parkinsonism is a common neurological sequela of carbon monoxide (CO)
      poisoning, but its pathophysiological mechanism has yet to be clarified.
      OBJECTIVES: To describe a married couple who were both affected by CO poisoning,
      but only 1 of whom developed CO-induced parkinsonism, and to discuss the possible
      underlying pathophysiological mechanism of CO-induced parkinsonism by comparing
      the neuroimaging findings of these patients. DESIGN AND SETTING: Case report from
      a clinical neurology department. PATIENTS: A married couple experienced CO
      poisoning simultaneously. One month later, only the husband gradually developed
      delayed sequelae, including parkinsonism and intellectual impairment. On detailed
      neurological examination, the husband showed mild but definite rigidity and
      bradykinesia, while no parkinsonian signs were observed in the wife.
      Neuropsychological examination revealed impaired memory and attention in both
      patients, but they were more severe in the husband than in the wife. Magnetic
      resonance imaging scans of the patients' brains disclosed diffuse high-intensity
      white matter signals in both patients and bilateral pallidal necrosis in the
      wife. Dopamine transporter imaging showed that the degree of dopamine neuronal
      loss was comparable between these patients. Magnetic resonance spectroscopy
      revealed more severe white matter damage in the husband than in the wife.
      Thirteen months later, neurological and neuropsychological examinations showed
      complete recovery from parkinsonism as well as intellectual impairment. Follow-up
      magnetic resonance spectroscopy also suggested remarkable improvements in white
      matter damage. CONCLUSION: These results support the role of white matter damage
      in producing parkinsonism after CO poisoning and highlight the possible
      usefulness of magnetic resonance spectroscopy in predicting delayed sequelae in
      patients after CO poisoning. Arch Neurol. 2000;57:1214-1218

PMID- 10927807
TI  - Migraine: the evolution of our knowledge.

PMID- 10927808
TI  - Health-related quality of life in neurology.
AB  - CONTEXT: In a climate of growing concern about costs of health care, professional
      accountability, and the effectiveness and efficiency of treatment, neurologists
      should understand measures of health-related quality of life (HRQoL) and
      appreciate both their values and their limits. OBJECTIVE: To provide a critical
      review of current concepts in the measurement of HRQoL, with particular emphasis
      on those pertaining to neurologic conditions. DESIGN: A selective overview of
      measurement strategies and specific instruments. SETTING: Clinical and research
      settings. PARTICIPANTS: Special attention to people with such conditions as
      multiple sclerosis and Parkinson disease. MAIN OUTCOME MEASURES: The utility and
      relevance to neurologists of available measures of HRQoL. RESULTS: There are both
      generic and condition- or disease-specific measures of HRQoL. Though many
      measures do not elicit response or are even offensive to people with such
      conditions as multiple sclerosis and Parkinson disease, other measures pertain
      directly to their circumstances and needs. CONCLUSIONS: Measures of HRQoL are
      both meaningful and relevant to neurologists. However, they must be refined
      enabled-and used in combinations to address the clinical and existential
      realities of many neurologic conditions. Arch Neurol. 2000;57:1224-1227

PMID- 10927809
TI  - Beneficial effect of bilateral pallidotomy on gait is unproven.

PMID- 10927810
TI  - Beneficial effect of bilateral pallidotomy on gait is unproven

PMID- 10927811
TI  - How dangerous is Viagra?

PMID- 10927812
TI  - Ask the doctor. I am 74 years old, and recently had a chest x-ray. My doctor told
      me it was fine. But I saw the report, and it said that I had calcification of the
      arch of my aorta. Should I be worried?

PMID- 10927813
TI  - Ask the doctor. The package insert with my cholesterol-lowering medication says I
      should take it in the evening, but my doctor says it doesn't matter. Which is
      right?

PMID- 10927814
TI  - Ask the doctor. I am generally healthy, but I had a heart attack last year. At my
      age, 78 years old, I find it hard to take it seriously when my doctor and my
      children tell me that I should be lowering my cholesterol and exercising. It
      seems to me that the idea of trying to prevent "premature" death is silly in
      someone my age. It's not like I feel ready to die, but it's hard for me to
      believe that prevention works in someone who has already gone beyond his "three
      score ten" years.

PMID- 10927815
TI  - By the way, doctor... My blood pressure is high in my doctor's office, but low
      when I take it at home on my blood-pressure monitor. My doctor says that I have
      white-coat hypertension, blood pressure that goes up in a doctor's office. She
      says it isn't medically dangerous, but can that be true?

PMID- 10927816
TI  - DARE: doubtful after 10 years.

PMID- 10927817
TI  - Child abuse and dissociation.

PMID- 10927818
TI  - By the way, doctor. At my last checkup, my doctor told me my blood pressure was
      elevated; it was 160/90. Over six weeks, I was able to get the diastolic pressure
      down to the low 80s through diet and exercise. But I have trouble keeping my
      systolic pressure down. It seems to fluctuate frequently and is especially
      dependent on my emotions. Any suggestions?

PMID- 10927819
TI  - Estrogen-progestin replacement and risk of breast cancer

PMID- 10927820
TI  - [Past, present, and future of "Letter to the editor" as a form of scientific
      communication].

PMID- 10927821
TI  - [Sharing and coordinating patient care between the hospital and primary care:
      some practical proposals].

PMID- 10927822
TI  - [Pediatric emergencies attended at a primary care clinic (I): Analysis of
      demand].
AB  - OBJECTIVES: To study paediatric emergencies in a primary care clinic, evaluating
      how suitable it is and the factors underlying the emergencies. DESIGN: A
      prospective, longitudinal study during the working days of alternate weeks
      between July 1 1996 and June 30 1997. SETTING: Urban paediatrics clinic, on the
      afternoon shift (2 to 9 p.m.), of the Vicente Soldevilla Primary Care Team (PCT)
      in Vallecas (Madrid). PARTICIPANTS: Population registered with the PCT: 2890
      children between 0 and 14. RESULTS: 723 emergencies were attended (consultations
      without prior appointment), which represented 21.1% of all non-scheduled
      consultations. The mean was 5.8 +/- 2.8 emergencies per day (range 0-13). They
      were more common on Mondays (6.8 +/- 2.4), in October (8.2 +/- 1.6) and in Autumn
      (5.8 +/- 2.6). 95% were of children registered with the PCT. Maximum attendance
      was between 4 p.m. and 7 p.m. (59%), coinciding with the on-demand clinic. 6.9%
      of the emergencies were unjustified, 51.3% were justified, and 41.8% could have
      asked for an appointment beforehand. The main reasons for attending as an
      emergency were: the symptoms beginning after the appointments desk had closed
      (43.2%), convenience (16.7%) and importance of the illness (12.4%). CONCLUSIONS:
      Emergencies make up a large proportion of consultations, and distort the
      organisation of the day's activities. 41.8% of cases could have requested a prior
      appointment. It is striking that 16.7% said they attended as an emergency for
      convenience. Children under 6 were those who attended emergencies most.

PMID- 10927823
TI  - [Pediatric emergencies attended at a primary care clinic (II): Epidemiological
      study]  .
AB  - OBJECTIVES: To analyse the reasons for consultation (RC), diagnoses, treatments,
      further tests (FC), whether resolved at PC level, referrals and personal history,
      at a paediatrics emergency clinic. DESIGN: A prospective, longitudinal study,
      during the working days of alternate weeks between July 1 1996 and June 30 1997.
      SETTING: Urban paediatrics clinic, on the afternoon shift (2 to 9 p.m.), of the
      Vicente Soldevilla Primary Care Team (PCT) in Vallecas (Madrid). PARTICIPANTS:
      Population registered with the PCT: 2890 children between 0 and 14. RESULTS: 723
      emergencies were attended. The main RC were: temperature (42.7%), catarrh (18.9%)
      and physical traumas (9.1%). The most common diagnoses were: tonsillitis/ENT
      focus (21.7%), upper passage catarrh (UPC) (15.9%) and acute gastro-enteritis
      (8.3%). 18.8% had some further test (x-rays 44.9% and urine cultures 43.4%). The
      most common treatments were antithermic, analgesic and anti-inflammatory drugs
      (41.8%), antibiotics (19.7%), oral tolerance and/or diets (9.8%) and trauma
      treatment (5.2%). 14.9% were treated at the health centre, 69.5% of which were
      trauma treatments. 95.8% of the consultations were resolved. The most common
      referrals (78.2%) were due to trauma. CONCLUSIONS: Temperature and catarrh
      symptoms were the most common RC in children under 10, and trauma in children
      over 10. Tonsillitis/ENT focus and UPC were the most common diagnoses in the
      under-10s, and trauma in the over-10s. Most requested further tests were X-rays
      and urine cultures. Most commonly prescribed medicines were antithermic,
      analgesic and anti-inflammatory drugs. Mainly trauma treatments were done at the
      health centre. Primary care is an effective filter of hospital emergencies.
      Traumas were the main cause of referrals to hospital.

PMID- 10927824
TI  - [Differences between young and elderly patients in a protocol for the diagnosis
      and follow-up of arterial hypertension]  .
AB  - OBJECTIVE: To determine possible differences between the control of hypertension
      in elderly patients and in young patients. DESIGN: Retrospective observation
      study of the differences between initial and final systolic and diastolic blood
      pressure, of their relationship to inclusion in medical treatment, and of the
      control obtained with different kinds of, and changes in, treatment, of drug
      association, periodic check-ups, vascular disease and risk factors. SETTING: The
      urban Azpilagana Health District in Pamplona. PATIENTS: 389 hypertense patients
      were studied retrospectively: 196 of 70 or over and 193 between 45 and 60. MAIN
      RESULTS: More older patients were treated medically (91.8% vs 84.5%, p = 0.024),
      and received combined two-drug treatment (30.1% vs 19.7%, p < 0.001), although
      the young people received more than two hypertension drugs more often (11.4% vs
      2.5%, p < 0.001). Final control (< 140/90) was achieved more often among young
      people (39.9% vs 26.5%, p = 0.005). In the older patients group initial higher
      diastolic pressure was related to final pressure control. More older patients had
      periodic check-ups at the health centre (73.3% vs 63.7%, p < 0.001), but this
      practice only improved relative control (< or = 140/90) in young people (p =
      0.001). Older patients used more diuretics (p < 0.001) and less beta-blockers (p
      < 0.001), with no differences for other hypertension drugs. CONCLUSIONS: There
      are differences based on age in treatment and control of hypertension patients.
      Older patients with diastolic hypertension are controlled more easily. Altogether
      and in both groups analysed, the percentage of people with normal pressure after
      treatment was higher than in other studies.

PMID- 10927825
TI  - [Minor surgery in primary care: consumer satisfaction].
AB  - OBJECTIVE: To find the satisfaction of patients undergoing minor surgery at
      health centres and describe the processes. DESIGN: Retrospective study of
      population seeking the service. SETTING: Health district. PATIENTS: 160 people
      who had minor surgery during a year. MEASUREMENTS AND MAIN RESULTS: Descriptive
      variables of everyone who had minor surgery were analysed: age, sex, type of
      intervention, pre-surgical diagnosis, anatomical-pathological diagnosis and
      informed consent. Over three weeks the patients were interviewed by phone with
      use of a satisfaction questionnaire. 160 interventions took place, 80% of which
      were then studied histologically, with an 83.16% concordance index. 65% of
      patients were interviewed. 15% had no telephone, 20% were not found, 95.56%
      considered they were well attended and 3.17% badly attended. 92.06% would choose
      the health centre again for procedures of a similar nature. 89.9% thought that
      the explanations they had received were sufficient. 4.4% thought that the room's
      hygiene was poor. CONCLUSIONS: Minor surgery in primary care was favourably
      received by users. Activity at our centre had good anatomical-pathological
      concordance.

PMID- 10927826
TI  - [Validation of the quality of life questionnaire in arterial hypertension (HQALY)
      for its use in Spain. Relationship between clinical variables and quality of
      life. Investigator Group of the HQALY study].
AB  - OBJECTIVE: To evaluate the measurement properties of the Hypertension Quality of
      Life (HQALY) questionnaire, under normal clinical practice conditions, and the
      relationship between quality of life and clinical variables in patients with
      hypertension. DESIGN: Observational, prospective and multi-centred study.
      SETTING: 92 primary care centres in Spain. PARTICIPANTS: 269 patients, of both
      sexes and over 17, with hypertension, stratified by age (18-44, 45-64 and over
      64), sex and organic complaint. 106 individuals over 17 with normal tension were
      chosen at random. INTERVENTIONS: Intensification of treatment in hypertense
      patients. MEASUREMENTS: Administration of the HQALY and the EuroQol-5D at every
      attendance (patients, basal and at a month; controls, basal). In addition, at the
      basal attendance social-demographic and clinical features were recorded, and at
      the attendance at a month the clinical features and changes in health status.
      MAIN RESULTS: Mean time of administration was 28 (23) minutes. VALIDITY: factor
      analysis showed two dimensions, state of mind and somatic manifestations, which
      correlated most closely with the dimensions of anxiety/depression (0.64) and
      pain/discomfort (0.55) on the EQ-5D, respectively. HQALY scores were higher
      (worse quality of life) in patients than in controls without hypertension (p <
      0.01). Reliability: intraclass correlation coefficient was 0.88 in state of mind
      and 0.76 in somatic manifestations. Cronbach's alpha was 0.96 and 0.89,
      respectively. Sensitivity: the "size of the effect" at a month from starting
      treatment for hypertension was 0.40. Hypertension for over 10 years, more organs
      affected, gravity and morbid obesity were associated with worse quality of life,
      especially in the state-of-mind dimension. Cardiac frequency correlated closer
      with state of mind than somatic manifestations. CONCLUSIONS: The HQALY is the
      first specific hypertension questionnaire developed in Spain which has been shown
      valid, reliable and sensitive to changes. However, the number of items on it must
      be reduced for routine use in clinical practice.

PMID- 10927827
TI  - [Intervention of the family physician in the diagnosis of cancer].
AB  - OBJECTIVE: To find the intervention of family doctors (FD) in diagnosing tumour
      pathology. DESIGN: Retrospective descriptive study. SETTING: Urban primary care
      centre. PATIENTS: Patients over 14 diagnosed with cancer. MEASUREMENTS: Selection
      of patients from the computerised records between November 1989 and March 1997.
      Review of clinical histories, analysing: 1. Personal details, 2. Type of cancer,
      3. Intervention of the FD in the diagnosis, 4. Symptom of initial consultation,
      5. Further tests requested by FD, 6. Interval between consultation and diagnosis,
      7. Survival and 8. interval between diagnosis and death. FD intervention in
      diagnosis was evaluated: 1. Impossible intervention, 2. No intervention, with
      suspect signs not valued (SSNV) or with suspect signs valued (SSV), 3. Diagnostic
      intervention, incomplete (Iin) or complete (Ico). RESULTS: 438 tumours were
      detected: in 256 men (59%) and 171 women (41%). The most common kind in men was
      lung cancer (46 cases, 17%), and in women breast cancer (59 cases, 34%). In 233
      cases (53%) the intervention of the FD was impossible. In 29 cases (6.5%) the
      FD's intervention was nil (15 cases with SSNV, 14 cases with SSV). Of the 174
      cases (39.6%) in which the FD intervened, full diagnosis was made in 40% (69
      cases). The mean of the interval between the first consultation and the diagnosis
      was significantly less when FD intervention existed, at 1.95 months (CI, 0.63
      1.06) in Ico and 2.9 months (CI, 0.51-2.19) in Iin, than when there was no
      intervention, with delays of 5.58 months (CI, 1.46-3.53) with SSNV and 10.5
      months (CI, 8.45-12.54) with SSV (p = 0.000). CONCLUSIONS: The family doctor can
      play an important part in cancer diagnosis. His/her active intervention can
      reduce the interval between consultation and diagnosis.

PMID- 10927828
TI  - [Analysis of the claims in a specialist primary care center].
AB  - OBJECTIVE: To analyze the written claims attended at a specialists unit of a
      Primary Health Care Center in Nou Barris, Barcelona. DESIGN: Evaluative
      observational study. SETTING: Health Care District of Nou Barris, with a
      population of 170,849. Period of study covers claims attended between 1-6-1996 to
      31-12-1998. PARTICIPANTS: 220 claims registered at a specialist unit of a primary
      health care center. MEASUREMENTS: Claimer's age and gender, heath care net of
      origin, claim's motive, claimed person or service and health care activity.
      Statistical analyses performed included descriptive techniques and Khi-square
      (chi 2) tests (alpha = 0.05). RESULTS: Cumulative incidence of claims was 4.03
      per 10,000 person-year in 1996, 4.70 in 1997 and 5.88 in 1998 (p = 0.0128). 220
      claims were analyzed, 53.1% of them came from women. Mean age was 51.12 +/- 15.8
      years. 60% of claims came from people using the traditional health care net, and
      40% from reformed health care net. Mean time of response was 12.3 +/- 12.7 days.
      Ophthalmology was the most claimed service (18.64%), followed by "the system"
      (13.64%), and "the center" (13.64%). 64% of claims pointed to specialists, and
      don't adjusted with their health care activity (p = 0.0001). Relative risk of
      being claimed at the specialists unit was 2.91, compared to the rest of the
      primary health care centers of Nou Barris in 1998. CONCLUSIONS: Health care
      user's claims become useful to detect some difficult aspects. However,
      improvements in the methodology of their evaluation are needed.

PMID- 10927829
TI  - [Primary care in mental health: concretizing patient-centered care].

PMID- 10927830
TI  - [The rural environment: a vision looking to the future (I)]. Rural Medicine
      Working Group of the semFYC].

PMID- 10927831
TI  - [The Ottawa ankle rules].

PMID- 10927832
TI  - [Consumption of non-steroidal anti-inflammatory drugs in basic health areas of
      the health region of Girona during 1997].

PMID- 10927833
TI  - [On the inaugural session of the XIX congress of semFYC].

PMID- 10927834
TI  - [Home care services debated].

PMID- 10927835
TI  - Outbreak of Escherichia coli O157:H7 leading to the recall of retail ground beef-
      Winnipeg, Manitoba, May 1999.

PMID- 10927836
TI  - Escherichia coli O157:H7 infections associated with ground beef and their control
      in Canada.

PMID- 10927837
TI  - Statement on immunization for Lyme disease (ACS-3). An Advisory Committee
      Statement (ACS). National Advisory Committee on Immunization (NACI).

PMID- 10927838
TI  - Supplementary statement on hepatitis A vaccine (ACS-4). An Advisory Committee
      Statement (ACS). National Advisory Committee on Immunization (NACI).

PMID- 10927839
TI  - Statement on alternate adolescent schedule for hepatitis B vaccine (ACS-5). An
      Advisory Committee Statement (ACS). National Advisory Committee on Immunization
      (NACI).

PMID- 10927840
TI  - Realigning Health Canada: form before function?

PMID- 10927841
TI  - Fulminant hepatitis A in patients with chronic liver disease.
AB  - Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV)
      infection. We report three cases of fulminant hepatic failure with death due to
      HAV infection in patients with pre-existing chronic liver disease. Data from the
      literature also indicate a high case fatality rate during HAV superinfection in
      patients with chronic hepatitis B, particularly those with cirrhosis, and in
      patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results
      are conflicting with some reports indicating a high fatality rate of HAV
      superinfection and others not, irrespective of the presence or absence of
      cirrhosis. Based on our observations and this review of the literature, we
      suggest that patients with chronic liver disease should be vaccinated against
      hepatitis A.

PMID- 10927842
TI  - The prevalence of intrinsic host risk factors associated with progressive disease
      in patients with chronic hepatitis C viral infections.
AB  - The prevalences of three risk factors that have been identified as important
      predictors of more progressive forms of chronic hepatitis C viral (HCV)
      infections (male gender, transfusion recipients and age greater than 50 years at
      the onset of infection) were documented by a retrospective chart review of 337
      HCV-infected patients attending an urban, hospital-based, viral hepatitis clinic.
      One hundred and ninety-five patients (58%) were male. One hundred and eighteen
      (35%) had received blood or blood product transfusions in the past, 33% of whom
      also gave a history of intravenous drug use. Approximately 5% of patients were
      over the age of 50 years at the estimated time of infection. Twenty percent of
      patients had two and 4% had all three risk factors. In conclusion, intrinsic host
      risk factors associated with progressive HCV infection were common in this
      patient population. If confirmed in other centres, these results suggest that the
      medical and financial demand on the health care system is likely to be
      appreciable unless effective and safe therapies for HCV are identified and
      implemented in the near future.

PMID- 10927843
TI  - [Drugs, Poverty and HIV: results regarding a provincial needle exchange program
      in Point de Reperes, Quebec].
AB  - In this study (n = 200), the characteristics of IDUs participating in a
      provincial needle exchange program (NEP) for more than 2 years (> 2 years) were
      compared with those of IDUs having participated for less than 2 years (< or = 2
      years). Compared to the < or = 2 years, the > 2 years were more often recipients
      of welfare (RC: 4.7), especially among the HIV-positive (RC: 62.0); tried
      quitting drugs more frequently (RC: 3.8); more often recommended the NEP to other
      IDUs (RC: 3.1); and more often requested being given shelter and longer opening
      hours (RC: 3.6). These results highlight the urgent need to improve and develop
      transitional and support services for the > 2 years. Preventive interventions
      that would reach out to the < or = 2 years where they live should also be
      implemented in close collaboration with organizations involved in mental health
      and drug use prevention.

PMID- 10927844
TI  - Government policies as a threat to health: findings from two Toronto community
      quality of life studies.
AB  - Community members, service providers, and elected representatives in two Toronto
      communities were asked to identify community factors influencing the health of
      community members. Many of the identified barriers to health related to
      government policies and actions. Cutbacks in federal transfers to provinces and
      provincial cutbacks in funding for agencies, reductions in social assistance,
      ending of new social housing, and other policy changes were seen as negatively
      impacting the health of the community and its members. These perceptions were
      remarkably consistent with emerging findings concerning the determinants of
      health. Implications for public health practice were considered.

PMID- 10927845
TI  - Gun availability and the use of guns for suicide and homicide in Canada.

PMID- 10927846
TI  - Time trends and sex patterns in Hodgkin's disease incidence in Canada, 1970-1995.
AB  - PURPOSE: To examine time trends and sex patterns in Hodgkin's disease incidence
      in Canada, from 1970 through 1995. METHOD: In addition to analyses of the secular
      trends and sex ratio in incidence rates, age-period-cohort models were fitted to
      estimate the effects on the trends. Age-specific male/female incidence rate
      ratios were examined for the disease and for its two major histologic subtypes.
      RESULTS: The overall age-adjusted incidence rate of Hodgkin's disease decreased
      significantly in males (3.5 per 100,000 in 1970-71 to 2.8 in 1994-95) but only
      slightly in females (2.4 per 100,000 to 2.3). There was a significant increase in
      the incidence among females aged 10-29 and among males aged 10-24, but a dramatic
      decrease among older ages. Age-period-cohort modelling showed that birth cohort
      and period effects were responsible for the observed trends in males and females,
      respectively. CONCLUSION: The risk factors responsible for Hodgkin's disease are
      different in females and males. Reproductive factors are likely to be associated
      with the occurrence of the disease in young women.

PMID- 10927847
TI  - Congenital anomalies ascertained by two record systems run in parallel in the
      Canadian Province of Alberta.
AB  - To assess the quality and appropriateness of Canadian Congenital Anomalies
      Surveillance System (CCASS), a system based on routine hospital
      admission/separation records, we compared the congenital anomalies ascertained by
      CCASS for the period of January 1, 1990 to December 31, 1993 in the province of
      Alberta with corresponding figures obtained from Alberta Congenital Anomalies
      Surveillance System (ACASS), a specific-purpose surveillance program collecting
      information on congenital anomalies from multiple sources with mechanisms to
      evaluate diagnosis. Rates of congenital anomalies estimated by CCASS tended to be
      higher. Agreement between CCASS and ACASS depended on diagnosis: for the
      International Clearinghouse for Birth Defects Monitoring System standard
      categories of congenital anomalies (except for anomalies of abdominal wall),
      agreement usually exceeded 50%; for less clear-cut diagnoses, it was well below
      50%. We conclude that routine medical records can be used for surveillance
      purposes for major congenital anomalies with clear-cut diagnosis.

PMID- 10927848
TI  - Increasing childhood trauma in Canada: findings from the National Population
      Health Survey, 1994/95.
AB  - Age-cohort variation in childhood trauma was examined in the present study. The
      data were taken from the 1994/95 Canadian National Population Health Survey of
      household residents (n = 15,106). Childhood trauma was measured by a seven-item
      index (items reflected physical abuse, fearful experiences, hospitalization,
      being sent away from home, and parental disturbance). Reported prevalence of
      childhood trauma increased with each successively younger age-cohort (range = 31%
      to 60%). Females showed a larger change than males, and age differences grew more
      pronounced as trauma exposure increased. The data suggest that childhood trauma
      has been on the increase over the last few decades. This is in accord with
      findings from other studies which showed that depression and social problems have
      also been on the rise. This suggests that adult psychiatric sequelae of early
      trauma can be expected to show an increase in future years.

PMID- 10927849
TI  - Are child pedestrians at increased risk of injury on one-way compared to two-way
      streets?
AB  - OBJECTIVES: To compare child pedestrian injury rates on one-way versus two-way
      streets in Hamilton, and examine whether the characteristics of child pedestrian
      injuries differ across street types. METHODS: The rates of injury per child
      population, per kilometre, per year were calculated by age, sex and socio
      economic status (SES). Child, environment and driver characteristics were
      investigated by street type. RESULTS: The injury rate was 2.5 times higher on one
      way streets than on two-way streets and 3 times higher for children from the
      poorest neighbourhoods than for those from wealthier neighbourhoods. SES, injury
      severity, number of lanes, collision location and type of traffic control were
      also found to be significantly different across street types. CONCLUSIONS: One
      way streets have higher rates of child pedestrian injuries than two-way streets
      in this community. Future risk factor and intervention studies should include the
      directionality of streets to further investigate its contribution to child
      pedestrian injuries.

PMID- 10927850
TI  - The relationship of pubertal status to body image, social physique anxiety,
      preoccupation with weight and nutritional status in young females.
AB  - The relationship of puberty to body image, social physique anxiety, preoccupation
      with weight and nutritional status was examined in 77 non-obese females (7-16
      years). Results showed that 34% of the pre-pubescent girls, 36% of the early
      pubescent girls and 76% of the post-pubescent girls were dissatisfied with their
      body shape. Social physique anxiety, determined by the SPAS scale, and
      preoccupation with weight, measured by the Eating Disorder Inventory were
      observed in all pubertal groups but were more evident in the early and post
      pubescent groups. No significant difference existed among the maturation groups
      in mean caloric and nutrient intake. The results showed that antecedents for
      developing an eating disorder existed in all maturational groups studied,
      although no health risk behaviours regarding nutritional status were observed.

PMID- 10927852
TI  - Gullible fools or desperate pragmatists? A profile of people who use rejected
      alternative health care providers.
AB  - Much research on alternative medicine seeks to discover why people use practices
      which orthodox medicine rejects as ineffective: rejected alternative medicine.
      However, to obtain a sample large enough for statistical analysis, many studies
      include as alternative health care, practices such as chiropractic or acupuncture
      which most doctors accept as effective for limited purposes: accepted alternative
      medicine. The 1994-95 National Population Health Survey shows Canadians who
      consult rejected alternative health care providers compared with those who
      consult accepted health care providers have similar incomes, more education,
      slightly fewer chronic diseases and slightly more good health habits. For both
      groups, alternative health care supplements orthodox health care rather than
      being an alternative to it. Two major differences emerge: women outnumber men
      more than two to one as opposed to being only a slight majority, and usage peaks
      in Quebec, not Western Canada.

PMID- 10927851
TI  - The health of Cree, Inuit and southern Quebec women: similarities and
      differences.
AB  - Using the data from a number of the surveys conducted over the last 10 years by
      Sante Quebec, this study examines the health characteristics of two populations
      of Aboriginal women of northern Quebec compared to those of women in the rest of
      the province. The northern populations had a larger proportion of young women.
      Aboriginal women have heavier family responsibilities than other Quebec women.
      Inuit women had a much higher prevalence of smoking and drug use. Alcohol
      consumption was less frequent in northern women, but the quantity consumed was
      higher compared to other Quebec women. Cree women tended to be more obese, had
      higher levels of blood glucose and lower levels of cholesterol. Inuit women
      tended to have lower rates of hypertension and higher rates of declared hearing
      problems and mental disorders. The similarities and differences observed among
      these three populations of women can assist decision-makers in setting priorities
      with regards to maintaining and improving their health.

PMID- 10927853
TI  - Do nutrition indicators predict death in elderly Canadians with cognitive
      impairment?
AB  - This study describes the independent association between nutritional risk and
      death in older adults diagnosed with cognitive impairment. Canadian Study of
      Health and Aging participants who completed a clinical exam and were diagnosed
      with cognitive impairment and had complete data for regression analyses were
      included (n = 735). Nutritional risk was defined as the presence of at least one
      abnormal nutrition indicator identified during the clinical exam (history of
      weight loss, abnormal serum albumin, poor appetite, body mass index < 20). Other
      covariates believed to influence mortality were modelled with nutritional risk
      using logistic regression. There were 373 deaths during the five-year follow-up
      period in this sample. Nutritional risk was found to independently increase the
      likelihood of death (OR = 1.6, 95% CI 1.1, 2.2) in these older adults suffering
      from cognitive impairment. Further work is required to determine if interventions
      can improve nutritional status and quality of life of these older adults.

PMID- 10927854
TI  - The health planning context and its effect on a user's perceptions of software
      usefulness.
AB  - This article reports a health planner's experience in using program planning
      software and the contextual factors that influenced her perceptions. The software
      examined (EMPOWER) is designed to support program planning for prevention of
      breast cancer through mammography screening. Use by a health professional in an
      urban hospital was examined through a case study approach. The user was
      interviewed at 3, 6, and 12 months following initial use. Transcripts were coded
      using Roger's characteristics of an innovation as a framework for categorizing
      the user's perceptions. Contextual factors identified as important in influencing
      her perceptions were open-coded and themes identified. The user referred to three
      contextual factors in describing characteristics of the innovation:
      implementation factors, user background, and work and community environment. The
      successful dissemination of software will depend not only on characteristics of
      the innovation, but also on situational circumstances that must be changed by, or
      accommodated in the technology.

PMID- 10927855
TI  - Partnering in and for heart health promotion: findings from a survey of community
      organizations.
AB  - This paper presents the results of a survey conducted with representatives (n =
      283) of community health agencies linked to heart health activity in Ontario in
      order to: 1) describe their levels of involvement in heart health promotion, 2)
      describe the nature and extent of partnering undertaken in the context of
      community-based heart health promotion, and 3) assess the extent to which
      community development approaches vis-a-vis partnering are being employed in
      Ontario heart health promotion. The survey included a series of questions
      regarding level of agency involvement in heart health promotion activities
      organized around four areas: tobacco, nutrition, physical activity and general
      heart health. Respondents were also asked to report the nature and extent of
      partnering that took place. Results indicate that levels of involvement varied
      significantly across activity area and by organization, although every agency
      type reported some level of involvement in each of the four activity areas.
      Overall, agencies surveyed continue to employ traditional settings (i.e., schools
      and community) as well as strategies (i.e., public education) but report a
      substantial amount of partnering and collaboration when undertaking community
      based heart health promotion activities.

PMID- 10927856
TI  - Re: Raphael D, Bryant T. Putting the population into population health.

PMID- 10927857
TI  - Re: Kendall P.R.W., Pearce M. Drug testing in Canadian jails: to what end? Can J
      Public Health 2000;91(1):26-28.

PMID- 10927858
TI  - Two outbreaks of VTEC O157 infection in northern England.

PMID- 10927859
TI  - Sexually transmitted disease quarterly report: anogenital warts and anogenital
      herpes simplex virus infection in England and Wales.

PMID- 10927860
TI  - Nitric oxide: a molecule of the millennium.
AB  - Recognition of Nitric oxide (NO) as the chemical entity of endothelium-derived
      relaxing factor (EDRF) has renewed the interest of the scientific community in
      the last decade. The outcome of research the world over is that the dreaded
      environmental pollutant is found to be a fundamental physiological mediator and
      effector. NO is synthesized endogenously by enzymes nitric oxide synthase (NOS)
      in specialized tissues from its precursor L-arginine. The L-arginine-NO
      biosynthetic pathway is involved in physiological processes such as vasodilation,
      memory, neuroprotection, peristalsis, penile erection, immune defense, various
      endocrine and exocrine secretions in various systems such as cardiovascular, CNS,
      reproductive and immune system. Small quantities of NO produced by constitutive
      enzymes mediate these physiological effects. The expression of inducible enzyme
      or overstimulation of constitutive enzymes leading to production of large
      quantities of NO is implicated in the cytotoxic effects observed in various
      disorders like AIDS, cancer, Alzheimer's, arthritis etc. In conclusion, NO is a
      'double edged sword' and the challenge before the scientific community is to
      develop strategies for using it to our advantage.

PMID- 10927861
TI  - Investigation of signal transduction pathways involved in melanoma cell
      spreading.
AB  - Integrins are a major family of heterodimeric adhesion receptors that are
      responsible for anchoring cells to extracellular matrix and they also can
      initiate intracellular signal pathways. Here parental and alpha 4-expressing
      human malignant melanoma cell lines were used to study the effect of protein
      kinase C (PKC), protein tyrosine kinases (PTKs) and intracellular Ca2+ on alpha 4
      beta 1-mediated cell spreading on VCAM-1. Incubation of melanoma cells with PKC
      inhibitor inhibited alpha 4 beta 1-mediated melanoma cell spreading completely.
      Effect of intracellular Ca2+ on melanoma cell spreading was also investigated by
      non-phorbol ester tumor promotor, thapsigargin, which blocks the ability of the
      endoplasmic reticulum to replenish stocks of calcium which naturally leak out
      into the cytosol leading to a transient increase in concentration of
      intracellular calcium. The results showed that alpha 4 beta 1-mediated spreading
      was also required intracellular calcium involvement. However, in the presence of
      PTKs inhibitor melanoma cells showed long, thin dendiritic projections compared
      to control cells. Previously, data was obtained from immunofluorescense
      experiments showed that after genistein treatment, alpha 4-expressing cells
      exhibited considerable amounts of alpha 4 integrin and PTKs in both the focal
      contact points as well as over the whole cell. PTKs inhibitor did not have any
      effect on alpha 4-expressing cells spreading. This could be related to the amount
      of the PTKs present in these cells.

PMID- 10927862
TI  - 90Sr-90Y biokinetics at incorporation determine the radiation burden to bone
      marrow.
AB  - The decay characteristics of 90Sr-90Y ensure that the mother and daughter
      nuclides exist in radioactive equilibrium, unless they get discriminated on the
      basis of their chemical properties, as it happens during metabolism. Although
      bone is the ultimate organ of deposition, the two nuclides arrive at this target
      organ over different biokinetic pathways. As 90Y is not excreted, it goes through
      transient deposition in the liver before being secondarily deposited in bone.
      This leads to a temporary radioactive excess of 90Y in bone. Since the decay
      energy of 90Y is by a factor of about 4 higher than that of 90Sr, the initial
      radiation burden to the bone marrow is primarily due to 90Y. This was estimated
      in rats by implanting LiF thermoluminescence dosimeters (TLD) in the marrow
      cavity of the femur. By calibrating the TLD against a known source of 90Sr-90Y,
      the absorbed dose rates and cumulative doses were determined as a function of
      time after incorporation. Two routes of administration were employed and their
      influence on the radiation burden is also shown.

PMID- 10927863
TI  - Immunohistochemical localization and correlation of p53 and PCNA expression in
      breast carcinoma.
AB  - The object of the present study is to detect the p53 tumour suppressor gene and
      proliferation cell nuclear antigen (PCNA) expression in breast carcinoma by
      immunohistochemistry and correlate them with the prognostic parameters. Total 35
      cases of primary breast carcinoma were studied and classified histologically.
      Paraffin sections were stained by using monoclonal antibody D07 for p53 protein
      and PC-10 for PCNA. Out of 35 cases, 16 (45.7%) were p53 positive and 25 (71.4%)
      were PCNA positive. The mean PCNA labelling index (PCNA LI +/- SD) was 58.97 +/-
      22.72 in tumors positive for both p53+ and PCNA+ while cases negative for p53-
      and positive for PCNA+ has higher PCNA LI +/- SD (59.24 +/- 18.97). The
      difference in the two groups was not significant. Most cases were positive for
      both p53+ and PCNA+ in the age group < 30 with higher mean PCNA LI +/- SD (62.20
      +/- 27.13) than in the group > 30 (57.88 +/- 18.47). In the pre-menopausal group
      57.1% cases were positive for p53+ with higher PCNA LI +/- SD (59.94 +/- 24.22).
      Maximum p53 and PCNA positivity was observed in grade III tumors (63.2% and
      84.2%). The mean PCNA LI +/- SD was also highest in grade III carcinomas (66.83
      +/- 13.97). No significant correlation was found between p53 and PCNA status with
      morphological type and tumour size except that logistic regression showed a
      positive correlation with tumour grade. Therefore the present study suggests that
      both p53 expression and PCNA are markers of poor differentiation in breast
      cancer.

PMID- 10927864
TI  - Hyperglycaemia in pregnancy: effects on the offspring behaviour with special
      reference to anxiety paradigms.
AB  - Maternal hyperglycemic effect was studied on the offspring behaviour. Offspring
      were obtained from diabetic rats by mating a normal father with a diabetic mother
      (NFDM), diabetic father with normal mother (DFNM) and diabetic father with
      diabetic mother (DFDM). Rats were rendered diabetic by injecting streptozotocin
      (STZ, 50 mg/kg i.p.) in citrate buffer. Offspring were subjected to various
      anxiety parameters including open field exploratory behaviour, elevated plus maze
      and zero maze behaviours, and the social interaction tests at the age of 8 weeks.
      The results indicate that offspring of NFDM and DFDM showed anxiogenic activity
      on the elevated plus maze zero maze and the social interaction test. Offspring of
      NFDM and DFDM exhibited hyper and emotional activity in the open field behaviour
      test. The behavioural alterations observed in the offspring were comparable to
      the behavioural alterations noted in STZ diabetic rat as reported earlier.
      Further offspring of NFDM and DFDM exhibited mild hyperglycaemia. No significant
      behavioural alterations in the offspring of DFNM were observed. It may be
      concluded, that exposure of offspring to diabetic environment in their foetal
      life can lead to anxiogenic/emotional behaviours in adult life.

PMID- 10927865
TI  - Effect of microinjections of 5-hydroxytryptamine and adrenaline in central grey
      on pain responsiveness during acute food deprivation in conscious rats.
AB  - To study the effects of microinjections of 5 hydroxytryptamine and adrenaline in
      central grey on pain responsiveness during acute food deprivation, experiments
      were conducted in nine male rats. Microinjections of 5 HT (10
      micrograms/microliter) and adrenaline (10 micrograms/microliter) were given in
      central grey before and at the end of 6, 12, 18 and 24 hr food deprivation and
      the effects on pain threshold, cardiorespiratory parameters and body temperature
      were noted. Observations showed that 5 HT increased the pain threshold
      (antinociception) significantly (P < 0.05) with no change in cardiorespiratory
      response and body temperature, adrenaline did not alter pain threshold with no
      change in cardiorespiratory response and body temperature. The observations
      suggest the possible existence of two types of monoaminergic receptors or
      pathways in the central grey.

PMID- 10927867
TI  - Effect of acute administration of isoproterenol on submandibular salivary gland
      of female rat.
AB  - The functions of salivary glands are under the regulation of both sympathetic as
      well as parasympathetic nerve fibers. Further, it has also been demonstrated that
      chronic administration of a beta-adrenergic agonist isoproterenol (IPR) results
      in hypertrophy and hyperplasia of submandibular gland [Schneyer C A, Am J
      Physiol, 203 (1962) 232]. Specific purpose of the present attempt was to look for
      metabolic responses of submandibular gland of oestrous female rats at very short
      intervals after 10 min of administration of 5, 10 and 15 micrograms of IPR to
      females in oestrous condition; pharmacological action and clearance time being
      only 8 min. The results indicated significant reduction in case of enzymic
      activities of phosphorylase, total ATPase and Na(+)-K+ ATPase. Cyclic AMP
      specific phosphodiesterase and succinate dehydrogenase activities were suppressed
      only with 5 micrograms dose, but with rising dose levels the effect was not so
      apparent. Protein content of the gland was reduced slightly by administration of
      IPR. Hence, it became clear that submandibular gland responds rapidly to IPR
      administration. Implications of these observations are discussed.

PMID- 10927866
TI  - Differential modulation of nociceptive responses to mu and kappa opioid receptor
      directed drugs by blood glucose in experimentally induced diabetes rats.
AB  - The study has evaluated the effect of diabetes associated hyperglycaemia on
      nociception and antinociception induced by morphine, buprenorphine and
      pentazocine in female albino rats. Rats were allocated into 3 groups of 20 each-
      group I consisted of control having normal blood glucose levels (BGLs), group II
      consisted of streptozotocin-induced diabetics (STZ-D) having hyperglycaemia and
      group III consisted of diabetic rats controlled with insulin treatment.
      Immediately before and 15, 30 min, 1, 2 and 3 hr after injection with test drugs,
      rats were subjected to a thermal noxious stimulus using tail withdrawal from hot
      water and tail-flick latencies (TFL) so generated were recorded. Similarly,
      before and 30, 45 min and 1 hr after injection with drugs rats were subjected to
      abdominal writhing with hypertonic saline and number of writhes were counted per
      90 sec. In STZ-D animals (BGLs 317.95 +/- 3.8 mg/dl) a decreased TFL with an
      increase in the number of writhes compared to control and diabetes controlled
      with insulin treatment was observed. Percent maximum possible effect of morphine
      (5 mg/kg, s.c.) and buprenorphine (2 mg/kg, s.c.) was significantly lower when
      compared to control as well as STZ-D controlled with insulin treatment groups.
      Similarly percent protection from writhing of morphine (0.05 mg/kg, s.c.) and
      buprenorphine (0.01 mg/kg, s.c.) was significantly less in comparison to control
      and STZ-D controlled with insulin treatment group. However, percent maximum
      possible effect of pentazocine (20 mg/kg, s.c.) and percent protection from
      writhing of pentazocine (1 mg/kg, s.c.) was significantly high in STZ-D rats when
      compared to control and STZ-D rats controlled with insulin treatment groups. The
      results suggest that both mu and kappa--opioid receptors may be modulated by
      blood glucose levels possibly involving cellular energetics mediated change in
      potassium (KATP) channels in females rats, albeit differentially.

PMID- 10927868
TI  - Antianaemic properties of ayurvedic drugs, raktavardhak, punarnavasav and navayas
      louh in albino rats during phenylhydrazine induced haemolytic anaemia.
AB  - Single injection of phenylhydrazine[PH] reduced the number of RBC and haemoglobin
      content; decreased myeloid; erythroid cell ratio in bone marrow and increased
      Cathepsin D activity in spleen of rats. Ayurvedic drugs raktavardhak,
      punarnavasav and navayas louh recovered the number of RBC and haemoglobin content
      and raised myeloid: erythroid cell ratio and normalised cathepsin D activities by
      counteracting the action phenyl hydrazine. The results confirm the claims of
      ayurveda that these drugs possess the potency to cure anaemia through protection
      of RBCs from haemolysis and simultaneously lowering cathepsin D activities from
      the spleen.

PMID- 10927869
TI  - Vitamin A mediated limb deformities in the common Indian toad, Bufo melanostictus
      (Schneider).
AB  - Several types of limb deformities were induced by vitamin A in B. melanostictus.
      These ranged from total suppression of all the limbs (ectromelia) to partial
      development of either the forelimb or the hindlimb or both (mesomelia) to
      reduction or absence of digits in either the forelimbs or hindlimbs or both and
      absence of long bones in either the forelimbs or hindlimbs or both (phocomelia)
      or duplication of the hindlimbs (polymelia). All the limb abnormalities were
      induced in the developing limbs of the tail amputated tadpoles of B.
      melanostictus following vitamin A treatment, which is all the more interesting.
      The results suggest that vitamin A induces the above mentioned abnormalities by
      either switching on or over-expressing or disrupting the limb-specific hox genes
      by yet unknown mechanisms.

PMID- 10927870
TI  - Differential C-heterochromatin distribution in two species of freshwater fish,
      Anabas testudineus (Bloch.) and Puntius sarana (Hamilton.).
AB  - Anabas testudineus (2n = 46) had the more conserved pattern of its C
      heterochromatin distributed mainly in the centromeric region, whereas Puntius
      sarana (2n = 50) exhibited a rather unorthodox pattern, many chromosomes showing
      interstitial, some telomeric and a few chromosomes showing centromeric C-band
      localization. Further, lateral asymmetry in distribution of heterochromatin was
      also noted in two pairs of chromosomes in P. sarana. The possible implications of
      the differential distribution noted in these two species has been discussed.

PMID- 10927871
TI  - Micropropagation of sweet orange, Citrus sinensis Osbeck. for the development of
      nucellar seedlings.
AB  - Protocol for micropropagation of elite plants of sweet orange (Citrus sinensis)
      through nucellar embryo culture has been standardized. Three to four nucellar
      embryos and a zygotic embryo could be excised from a single mature seed and
      successfully generated as healthy plants in basal MS medium. MS medium
      supplemented with NAA (1 mg/L) or 2, 4.D (1 mg/L) promoted callus development in
      both nucellar and zygotic embryos. GA3 (1 mg/L) enriched medium induced plantlets
      initiation but their growth was very poor. No significant differences were
      observed between initial growth patterns of nucellar and zygotic seedlings
      developing from the same ovule. Five to six shoots were obtained from collar
      region of both category of embryos in MS medium supplemented with BAP (1 mg/L)
      within 60 days of inoculation. The number of plantlets were almost doubled after
      their transfer in the same medium and culture for another 30 days. Higher doses
      of BAP resulted in initiation of callus directly from the embryos. The
      regenerated shoots (2-3 cm) could be rooted in MS medium supplemented with either
      only NAA (0.75 mg/L) or NAA (0.50 mg/L) and IBA (2.0 mg/L). A number of plantlets
      could be obtained from a nucellar embryo grown shoot within a limited time
      period.

PMID- 10927872
TI  - In vitro multiplication of Nothapodites foetida (Wight.) Sleumer through seedling
      explant cultures.
AB  - In vitro multiplication of Nothapodites foetida (Wight.) Sleumer was achieved
      using axenic seedling explant cultures. Isolated nodes (1.0-1.2 cm) and shoot
      tips (1.0-1.5 cm) cultured in Murashige and Skoog's agar medium containing
      varying concentrations of TDZ, BA and combinations of 2iP and GA3. Single shoot
      (0.8-1.2 cm) was regenerated in each culture after 6 weeks. Axillary shoots were
      then excised and recultured for 8 weeks in medium containing TDZ (0.05 mgL-1)
      which formed shoots (about 4 in no.; 2 cm) from the basal node. Axillary branches
      (2) which formed on 60% of these shoots after 10-12 weeks of culture were
      separated and recultured in the same medium for 8 weeks. Three shoots (0.8-1.0
      cm) per culture were regenerated. Shoots of 0.8-1.8 cm length were subcultured on
      a low cytokinin (0.01 mgL-1 TDZ) regime to induce shoot elongation (2.0-3.5 cm)
      in 4 weeks. Shoot cuttings were rooted (60%) in the medium containing IBA (1.5
      mgL-1). Rooted plantlets established in pots (90%) after hardening resumed normal
      growth in 3 months.

PMID- 10927873
TI  - Hypoglycemic activity of bio-tea in mice.
AB  - Administration of bio-tea (1.71 ml/kg) to normal albino mice caused hypoglycemia
      after 30 min which reached to maximum after 2 hr with a significant decrease in
      blood sugar level (BSL) and became normal beyond 8 hr. In alloxan-induced
      diabetic albino mice, repeated treatments of bio-tea for 3 days (five doses)
      brought about a significant fall in mean BSL. Continuous decrease in BSL was
      observed after 4 hr of administration of last dose of bio-tea. Hypoglycemic
      effect was persistent in alloxan-induced diabetic mice. Effect on glucose
      tolerance test showed a significant fall in BSL of bio-tea treated animals after
      1 hr of glucose treatment indicating hypoglycemic effect of bio-tea.

PMID- 10927874
TI  - Ascorbate induced cross-linking of oxyhemoglobin subunits.
AB  - Ascorbic acid during oxidation in vitro can generate H2O2 which induces non
      disulphide covalent cross-linking of coincubated oxyhemoglobin. The cross-linking
      phenomenon mediated by H2O2 takes place possibly without the involvement of
      hydroxyl radicals as evident from the failure of radical scavengers like mannitol
      and dimethyl sulphoxide as well as metal-chelator, to inhibit the process. This
      pro-oxidant effect of ascorbic acid may have physiological significance in red
      blood cells in vivo.

PMID- 10927875
TI  - Detection of Theileria annulata carrier cattle by PCR.
AB  - A simple method for treating bovine blood samples for direct detection of T.
      annulata in carriers, after polymerase chain reaction (PCR) amplification of
      small subunit ribosomal RNA (SSU rRNA) gene is described. The threshold of
      detection of the PCR-assay was an erythrocytic parasitaemia of 0.00008%
      corresponding to 16 infected bovine erythrocytes. In 50 known carriers, 42 were
      positive in PCR, in which 8 cattle revealed presence of T. annulata in stained
      blood smear under microscope.

PMID- 10927876
TI  - Effect of norepinephrine on growth of Salmonella and its enterotoxin production.
AB  - Salmonella typhimurium was cultured in presence or absence of norepinephrine in
      conditioned media. Two conditioned media containing bovine and pig serum were
      prepared. Supplementation of fresh cultures with norepinephrine (5 x 10(-5) M per
      mL of medium) resulted in ten-fold increase in growth as compared to controls. No
      significant difference in growth of organisms in media containing bovine and pig
      serum was observed. Growth was more in culture incubated under shaking condition
      than in non-shaking condition. Enterotoxin production increased by two to eight
      folds in the medium supplemented with norepinephrine.

PMID- 10927877
TI  - Effect of feed on larvae of Macrobrachium malcolmsonii (H. Milne Edwards) reared
      in synthetic brackishwater.
AB  - Freshwater prawn, Macrobrachium malcolmsonii, has potential for aquaculture.
      Larvae of M. malcolmsonii were reared in synthetic brackishwater using commercial
      salts. Live and artificial feeds were provided to larvae either individually or
      in combination. Survival was significantly higher when larvae were fed with live
      feed only. However, larvae fed with artificial feed showed significantly lower
      survival. Survival was significantly higher when Artemia combined together with
      other feeds. Despite its limitations, synthetic brackishwater can be used for
      freshwater prawn seed production.

PMID- 10927878
TI  - Effect of solvent residues of Vitex negundo Linn. and Cassia fistula Linn. on
      pulse beetle, Callosobruchus maculatus Fab. and its larval parasitoid, Dinarmus
      vagabundus (Timberlake).
AB  - Effect of solvent residues of Vitex negundo L. and Cassia fistula L. leaves (0.5
      and 1%) was studied on egg laying and adult emergence of Callosobruchus maculatus
      Fab. and on percentage of larval parasitism by Dinarmus vagabundus (Timberlake).
      Cowpea seeds treated with methanol and aqueous extract of Vitex, at these
      concentrations (0.5 and 1%), significantly reduced the number of eggs and
      emergence of F1 adults of C. maculatus. Both Vitex and Cassia extracts did not
      affect the percentage of parasitism by D. vagabundus on C. maculatus grubs.

PMID- 10927879
TI  - Protease from Sporosarcina sp. RRLJ 1.
AB  - Protease was isolated from Sporosarcina RRLJ1 which was collected from acid tea
      (Camellia sinensis) plantations. It showed potential for production of the enzyme
      for commercial purposes. The study revealed that optimum pH for growth of the
      organism was 6.5-7 and supplement of casein (1%) in the medium was required for
      production of protease. Enzyme production and enzyme activity was maximum in 72
      hr old broth culture. Maximum activity of the enzyme was found at pH 6.5.

PMID- 10927880
TI  - Regulation of siderophore production by iron Fe(III) in certain fungi and
      fluorescent pseudomonads.
AB  - Regulation of siderophore production in response to iron concentration in the
      medium was examined. Threshold concentration was recorded for twenty fungi and
      three rhizobacterial pseudomonads. Organisms showed difference in threshold
      values at which they stopped siderophore elaboration. In nine fungi (3
      aspergilli, 1 penicillium, N. crassa, F. dimerum and 3 mucors) siderophore
      production was repressed at 3 microM Fe(III). Siderophore production was
      repressed at 27 microM of Fe (III) in 3 aspergilli, 2 penicillia and 3
      pseudomonads. Rest of the fungi had cut off values at 6, 9, 15, 21 microM of
      Fe(III) concentration.

PMID- 10927881
TI  - Spin-trapping detection of superoxides in polymorphonuclear leukocytes stimulated
      with serum-opsonized zymosan.
AB  - To clarify where oxygen radicals are generated in polymorphonuclear leukocytes
      (PMNs) during phagocytosis, superoxides (O2-) from opsonized symosan (OZ)-
      stimulated human PMNs were detected by the ESR and spin-trapping methods. PMNs
      were preactivated with OZ for the indicated periods of time at 37 degrees C. Then
      a spin-trapping agent, 5, 5-dimethyl-1-pyrroline N-oxide (DMPO), was added to
      them, and they were further incubated for 30 sec for ESR observations. The ESR
      spectra consisted of two components due to the DMPO-OOH and DMPO-OH spin adducts.
      To clarify where these spin-adducts were present, cells were separated from
      extracellular fluid by brief centrifugation and resuspended in Hanks' balanced
      salt solution. ESR examination of two fractions showed that the DMPO-OOH adducts
      was present in the cell fraction, whereas the DMPO-OH adducts were present in the
      extracellular fluid. When DMSO was used as a scavenger of hydroxyl radicals
      (.OH), DMPO-CH3 adducts were observed in the fluid fraction but not in the cell
      fraction. Both spin adducts were completely abolished by Cu, Zn-SOD but not
      catalase. These results indicated that O2- were produced inside phagosomes of OZ
      stimulated PMNs and .OH were produced outside them by spontaneous decomposition
      of the DMPO-OOH adducts.

PMID- 10927882
TI  - Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of
      humans, in rats and monkeys.
AB  - To establish a useful animal model of Itai-Itai disease (IID) of humans, we
      conducted the following experiments. Experiment 1: Toxic effects of Cd were
      compared between ovariectomized (OX) and non-OX rats after daily, intravenous
      injection of cadmium (Cd) chloride for 14 days. In this experiment, we
      demonstrated that OX rats were more susceptible to Cd-induced nephrotoxicity and
      hepatotoxicity than non-OX rats. Experiment 2: OX rats were injected with Cd at
      doses of 1.0 and 2.0 mg/kg, 5 days a week, for 13 weeks. The bone Cd content was
      gradually increased for 13 weeks in a dose-dependent manner. Calcium and
      phosphorus contents in the bone and serum levels of parathyroid hormone and
      osteocalcin were not significantly different between Cd-treated and control rats.
      Mild osteomalacic lesions in the cortical bones of the midshaft haversian canals
      as well as chronic nephropathy appeared in the rats of the 2.0 mg/kg group.
      Experiment 3: OX rats were treated with Cd at doses of 0.5 and 0.05 mg/kg for 70
      weeks. The rats of the 0.05 mg/kg group showed slight anemia and mild
      degeneration of tubular epithelium after 50 weeks of treatment. In the 0.5 mg/kg
      group, the rats showed definite osteomalacia of bones and nephrosclerosis. The Cd
      concentration in the bones increased for the first 25 weeks, but was replaced
      gradually with iron at from 50 to 70 weeks of the administration period. Iron
      deficiency anemia appeared in the 0.5 mg/kg group at from 12 to 25 weeks, and
      changed to renal anemia after 50 weeks of administration. The anemia at 50 and 70
      weeks was normocytic and normochromic, and serum erythropoietin levels were not
      elevated in response to the decrease of hemoglobin concentrations of red blood
      cells. Experiment 4: Ten, OX cynomolgus monkeys were given intravenous injections
      of 0, 1.0 or 2.5 mg/kg/day Cd, 2 or 3 days per week, for 13 to 15 months.
      Normocytic and normochromic anemia, renal lesions characterized by tubular
      atrophy and interstitial fibrosis (Cd nephropathy), and bone lesions
      characterized by an increase of osteoid and osteopenia (Cd osteopathy) were
      induced in the monkeys treated with Cd. These results demonstrated that chronic
      cadmium toxicosis similar to IID of humans was reproducible in rats and monkeys
      by repeated intravenous injection of Cd and that a disease entity closely
      resembling IID of humans could be induced in experimental animals by chronic Cd
      toxicosis without participation of malnutrition, vitamin D deficiency, impaired
      absorption at the intestinal mucosa or multiparous birth.

PMID- 10927883
TI  - Isolation of Pseudomonas aeruginosa from Ushubetsu River water in Hokkaido,
      Japan.
AB  - To provide information on the ecology of Pseudomonas aeruginosa in nature,
      bacteriological surveillance was performed in the defined area in Hokkaido,
      Japan. P. aeruginosa was isolated from water samples of Ushubetsu River in the
      down stream from the urban area of Asahikawa. P. aeruginosa was isolated from
      fecal samples of pigs but not from samples of soil of a tomato field, sand of
      sandboxes in vest-pocket parks, fresh vegetables, or feces of wild deer. The
      present results indicate that P. aeruginosa strains isolated from the river water
      is originated from the environment of human activity and not from wild life or
      domestic animals.

PMID- 10927884
TI  - Isolation of fungi from rose bush thorns.
AB  - Rose bush thorns from plants in the Oklahoma City area were cultured to determine
      the prevalence and species of fungi present. One hundred fifty isolates grew from
      thorns on 103 plants. All thorns harbored at least one species, while one thorn
      had five species of fungi. Of the 21 fungal species isolated, all are known human
      pathogens, although most rarely cause disease in immunocompetent individuals.
      Alternarium sp., Bipolaris sp., Aspergillus niger, Curvularia sp., and Fusarium
      sp. were the most common fungi, accounting for 75% of the isolates. Sporothrix
      schenckii, an organism often associated with rose bushes, was found on thorns of
      only two plants. Findings of this study suggest that since fungi are common
      inhabitants of roses, individuals who experience rose-thorn punctures are at
      increased risk of acquiring fungal infections, especially if they are
      immunocompromised.

PMID- 10927885
TI  - Alcohol consumption among the elderly: dispelling the myths.
AB  - Do old people drink? Community surveys suggest that alcohol consumption is lowest
      among elders compared to any other age group, and that patterns of drinking are
      relatively stable across mid-to-late life. But is this an accurate portrayal of
      those individuals seeking medical guidance? In other words, what is the
      likelihood of alcohol abuse or misuse among the typical hospital, outpatient
      clinic, or emergency room patient? How difficult is it to spot potential alcohol
      misuse among the elderly? The purpose of this paper is to address these questions
      and to assist physicians of the medical community in the important function of
      early detection and prevention of alcohol abuse/misuse in patient populations.

PMID- 10927886
TI  - Medschool.com: opportunity or threat?

PMID- 10927887
TI  - Where is self-regulation going?

PMID- 10927888
TI  - Dealing with amalgam waste.

PMID- 10927889
TI  - Dealing with amalgam waste.

PMID- 10927890
TI  - Cosmetic dentistry.

PMID- 10927891
TI  - U.S. Surgeon General report reveals profound disparities in oral health of
      Americans.

PMID- 10927892
TI  - Dealing with fraud and abuse.

PMID- 10927893
TI  - Screening for common oral diseases.

PMID- 10927894
TI  - How dentists can avoid getting into hot water.

PMID- 10927895
TI  - Management of extensive carious lesions in permanent molars of a child with
      nonmetallic bonded restorations--a case report.
AB  - The badly decayed molar teeth of a 12-year-old were restored using resin
      composite and ceramic restorations. The maxillary first left permanent molar,
      which had an extensive carious lesion that had destroyed most of the coronal hard
      tissues of the tooth, was restored to shape and function with a heat-treated
      resin composite onlay restoration. The restoration was followed up for two years.
      The mandibular right first molar had a failing large amalgam restoration with
      extensive recurrent caries. After a three-month period of pulp-capping, the tooth
      was restored with a bonded ceramic onlay restoration. A nine-month follow-up of
      this restoration is provided. The maxillary right first molar, which also had a
      failing large amalgam/resin composite restoration, was restored with a direct
      resin composite restoration. Under traditional treatment regimens, these
      extensive cavities would have been treated using more invasive procedures such as
      pin-retained restorations or elective root canal therapy, post placement, core
      build-up and crowning. Bonded non-metallic restorations avoid the trauma, time
      and cost that accompany such extensive procedures and offer a more conservative
      approach.

PMID- 10927896
TI  - Tobacco-associated lesions of the oral cavity: Part II. Malignant lesions.
AB  - Nonmalignant tobacco-associated lesions of the oral cavity were discussed in the
      first part of this two-part article. Here, we describe malignant lesions
      associated with tobacco use, basic biopsy principles for such lesions and
      intervention strategies that dental professionals may use to reduce the chances
      of their patients developing precancerous lesions or primary malignancies.

PMID- 10927897
TI  - The history of dental programs for older adults.
AB  - Compared with other age groups, the elderly have less access to oral health care
      services and poorer oral health status. Most provinces have no publicly funded
      programs to address these inequities and the volunteer efforts of professionals
      and hospital-based programs have had little effect. In Ontario, two expert
      committees have called for seniors' programs augmented by a strong outreach
      component to be delivered by public health services. Their recommendations have
      not been implemented and, worse, some public health programs have lost the
      capacity to maintain the preventive services they once provided. The development
      of public policy to address the needs of the elderly is thwarted by the narrow
      definition of public health problems, the reluctance of the dental profession to
      lobby for public funding, the bias toward investment in younger groups, and the
      persistence of a "reverse public funding program" whereby the employed, more
      affluent receive dental care as a tax-free benefit and the retired, lower-income
      elderly pay in after-tax dollars.

PMID- 10927898
TI  - Problems of an aging population in an era of technology.
AB  - With the substantially growing number of elderly persons in Canada and the rest
      of the developed world, the need for adequate health and social care will
      increase. Health and social service providers must develop policies and programs
      allowing the elderly to lead rich and independent lives for as long as possible.
      As advances in age-related diseases are made, the elderly will potentially live
      longer and lead more active and fulfilling lives. Society, governments and those
      involved in the care of the elderly must meet the new challenges of this aging
      population in a humane and respectful way.

PMID- 10927899
TI  - Unconventional dentistry: Part I. Introduction.
AB  - This is the first in a series of five articles providing a contemporary overview
      and introduction to unconventional (alternative) dentistry (UD) and correlation
      with unconventional (alternative) medicine (UM). UD is analogous to and
      conceptually inseparable from UM. Dentists should learn about UD and UM and be
      aware of evidence on the safety and effectiveness of treatments and procedures.
      While being skeptical of promotions, dentists should be able to accept and
      encompass science-based advances and reject unproven and disproven methods.
      Incorporating selected unconventional methods with conventional dentistry in
      selected patients for specific purposes may be useful to both patients and
      dentists. Improved education in critical thinking, research, science, medicine,
      behaviour, communication and patient management is needed.

PMID- 10927900
TI  - Percutaneous microcompression of the trigeminal ganglion for elderly patients
      with trigeminal neuralgia and patients with atypical trigeminal neuralgia.
AB  - Percutaneous microcompression of the trigeminal ganglion (PMTG) was performed in
      nine elderly patients (> 70 years) with trigeminal neuralgia and six patients
      with atypical neuralgia under short-acting anesthesia using propofol. Two
      patients had postherpetic neuralgia and two had postoperative neuralgia following
      removal of a posterior fossa neurinoma. Four patients had recurrent neuralgia
      following microvascular decompression (MVD). PMTG provided complete relief in 10
      patients and the other five patients reported at least 50% improvement. No major
      complications occurred. PMTG is effective for typical trigeminal neuralgia in
      elderly patients, patients with atypical trigeminal neuralgia, and patients with
      recurrence after MVD.

PMID- 10927901
TI  - Spinal cord stimulation for cerebral vasospasm as prophylaxis.
AB  - Cervical spinal cord stimulation (SCS) was used to increase cerebral blood flow
      (CBF) in 10 patients with secured cerebral aneurysms in Hunt and Hess grade 3 or
      4 and with Fisher group 3 subarachnoid hemorrhage (SAH). The patients underwent
      preemptive electrical stimulation through a percutaneous lead following aneurysm
      surgery. All patients also received hypervolemic therapy and nicardipine.
      Efficacy of the treatment was evaluated using xenon computed tomography and
      cerebral angiography. The CBF in the distribution of the middle cerebral artery
      significantly increased following SCS (p < 0.05). Four of 10 patients showed
      angiographic vasospasm, but none developed severe sequelae of cerebral vasospasm.
      The overall outcome was good or excellent in seven of the 10 patients. No serious
      adverse effects due to SCS were observed. Fluid management and calcium antagonist
      have a beneficial effect on cerebral vasospasm following SAH, but is not
      tolerated or is ineffective in some patients. SCS as an adjunctive therapy for
      cerebral vasospasm following SAH may have a favorable effect on outcome.

PMID- 10927902
TI  - Traumatic trochlear nerve palsy following minor occipital impact--four case
      reports.
AB  - Four patients presented with transient trochlear nerve palsy following occipital
      impact. The impact was slight in all patients, and neuroimaging found no lesions
      of the nerve. Three patients had delayed onset. Two patients did not complain of
      diplopia, but were only aware of blurred vision. In such patients, the head
      tilting test was useful for diagnosis. Minor occipital impact can cause trochlear
      nerve palsy, which requires careful neurological examinations to identify.

PMID- 10927903
TI  - Sigmoid sinus thrombosis after mild closed head injury in an infant: diagnosis by
      magnetic resonance imaging in the acute phase--case report.
AB  - Intracranial sinus thrombosis following a mild closed head injury without a skull
      fracture or intracranial hematoma is extremely rare. A 23-month-old girl
      presented with vomiting and gait ataxia 1 day after occipital trauma. Computed
      tomography revealed a slightly increased density area in the region of the left
      sigmoid sinus. T1-weighted magnetic resonance (MR) imaging demonstrated an
      isointense area in the left sigmoid sinus and T2-weighted imaging showed a
      hyperintense area reflecting the characteristics of oxyhemoglobin. MR angiography
      and cerebral angiography indicated occlusion of the left sigmoid sinus. After 4
      days of conservative treatment, her symptoms subsided completely. Follow-up MR
      angiography and cerebral angiography showed recanalization of the sigmoid sinus.
      The MR images and MR angiograms were useful for both early diagnosis and follow
      up. Treatment should reflect the severity of individual cases, and early
      diagnosis will help achieve a good outcome.

PMID- 10927904
TI  - Transarterial embolization with HEMA-MMA of variant convexity-superior sagittal
      sinus dural arteriovenous fistula--case report.
AB  - A 62-year-old male presented with a variant dural arteriovenous fistula (DAVF)
      within the wall of the convexity-superior sagittal sinus, fed by branches of the
      bilateral external carotid arteries and only cortical venous drainage despite the
      presence of a patent sinus. Transarterial embolization with poly(2-hydroxyethyl
      methacrylate-co-methyl methacrylate) (HEMA-MMA) was performed, resulting in
      complete obliteration of the DAVF. Embolization with HEMA-MMA is an effective and
      safe procedure for the treatment of DAVF.

PMID- 10927905
TI  - Bilateral simultaneous thalamic hemorrhages--case report.
AB  - A 54-year-old male presented with bilateral simultaneous thalamic hemorrhages
      manifesting as semicoma, tetraplegia, and skew deviation. Magnetic resonance
      imaging and angiography demonstrated no lesions responsible for the bleeding.
      Coagulant factors were within normal ranges. The cause of these hemorrhages was
      considered to be hypertension. Conservative treatment was performed. He was
      discharged with serious neurological deficits.

PMID- 10927906
TI  - Pineal region cavernoma--case report.
AB  - A 45-year-old male presented with a rare pineal region cavernoma. Magnetic
      resonance (MR) imaging confirmed the preoperative diagnosis. The tumor was
      totally excised. The patient was subsequently cured. Analysis of 15 reported
      cases found a slight female preponderance. The second and third decades were the
      most common age group. The course of pineal cavernomas can be complicated by
      hemorrhage, occlusion of cerebrospinal fluid pathways, and focal neurological and
      neuroendocrine symptoms but no specific clinical features. However, MR imaging
      has high sensitivity and the specificity for the diagnosis of pineal cavernoma.
      Total microneurosurgical excision is the treatment of choice, and patients had an
      excellent outcome. Stereotactic biopsy can be potentially dangerous because of
      the risk of hemorrhage. The use of radiosurgery requires evaluation of long-term
      risks and safe dose levels. Total excision of the pineal cavernoma using
      microsurgical techniques is the choice of treatment in young and healthy patients
      since there is an increased risk of recurrent hemorrhage and progressive
      neurological decline. A conservative approach is preferred in older patients.

PMID- 10927907
TI  - Superficially-located oligodendroglioma associated with intratumoral and
      peritumoral cysts--case report.
AB  - A 72-year-old male presented with a superficially-located oligodendroglioma
      associated with intratumoral and peritumoral cysts. Neuroimaging showed the outer
      cyst wall as enhanced but not the inner cyst wall. The outer cyst was removed and
      a biopsy taken of the solid component. The inner cyst wall appeared to consist of
      non-neoplastic tissue. Histological examination showed the tumor was an
      oligodendroglioma with tumor cells in the outer wall. The outer cyst was probably
      the result of blood-brain barrier disruption and intratumoral hemorrhage. The
      inner cyst probably resulted from reactive gliosis or peritumoral edema. Cyst
      formation in intraaxial tumors occurs through similar mechanisms to those of
      extraaxial tumors.

PMID- 10927908
TI  - Pituitary stone--case report.
AB  - A 50-year-old male with acromegalic features presented with a pituitary stone in
      a growth hormone-secreting adenoma. Endocrinological examination showed "low
      growth hormone acromegaly." The serum growth hormone level responded to the
      thyrotropin-releasing hormone test and was not suppressed by oral glucose
      loading. Neuroimaging revealed an adenoma including a large calcification
      (pituitary stone) located in the right lateral wing. The adenoma with stone was
      totally removed by transsphenoidal surgery. The patient regained almost normal
      response of serum growth hormone. Histological examination showed the stone was
      composed of thick calcification surrounded by necrotic adenoma tissue and chronic
      hemorrhage. Large intratumoral pituitary stone is very rare, although
      calcification is sometimes observed in the adenoma capsule. The long history of
      this disease and previous apoplexy within the tumor may have caused the pituitary
      stone in this patient.

PMID- 10927909
TI  - Retro-odontoid massive calcium pyrophosphate crystal deposition--case report.
AB  - An 86-year-old male presented with progressive myelopathy due to retro-odontoid
      massive deposits of calcium pyrophosphate dihydrate (CPPD) crystals. Magnetic
      resonance imaging revealed a non-enhanced isointense extradural mass on the T1
      weighted image and heterogeneously intense mass on the T2-weighted image.
      Computed tomography showed typical punctate and linear calcifications within the
      mass. The mass was resected via a lateral approach resulting in marked
      improvement of the symptoms. Histological examination revealed birefringent
      rhomboid crystals consistent with CPPD. CPPD deposition should be considered in
      the differential diagnosis of retro-odontoid extradural mass because surgical
      therapy is beneficial even for elderly patients.

PMID- 10927910
TI  - A comparison of the MicroCount Digital System to plate count and membrane
      filtration methods for the enumeration of microorganisms in water for
      pharmaceutical purposes.
AB  - The enumeration of microorganisms in water for pharmaceutical purposes using the
      MicroCount Digital System (Millipore Corporation, Bedford, MA) was compared to
      the USP-recommended Pour Plate and Membrane Filtration Count methods. A study,
      using a pure culture of Buckholderia cepacia, ATCC#25416, showed that the
      accuracy, precision, reproducibility and linearity of the MicroCount ATP
      Bioluminescence System was equivalent to or better than the traditional methods.
      When the MicroCount System was used to monitor purified water and water for
      injection taps in a pharmaceutical plant over a month, comparable counts to the
      traditional methods were obtained within 24 hours compared to 48 to 72 hours with
      the other methods. The effectiveness of the memory device used for the isolation
      of colonies for characterization was demonstrated by comparing the number and
      pattern of the positive wells in the MicroCount plates with the isolation of
      colonies on the microbial count agar plates. The recovery on agar plates,
      although slightly higher, was not statistically different to the MicroCount
      plates. The predominated microorganisms isolated using all three methods were
      Ralstonia pickettii, Bacillus sphaericus, Stenotrophomonas maltophia, and a
      Staphylococcus species.

PMID- 10927911
TI  - Pharmaceutical development of a parenteral lyophilized formulation of the novel
      antitumor agent aplidine.
AB  - Aplidine is a naturally occurring cyclic depsipeptide isolated from the
      Mediterranean tunicate Aplidium albicans. Aplidine displays promising in vitro
      and in vivo antitumor activities against various solid human tumor xenografts and
      is therefore developed now for clinical testing. The aim of this study was to
      develop a stable parenteral pharmaceutical dosage form for clinical Phase I
      testing. Aplidine raw material was characterized by using several chromatographic
      and spectrometric techniques. These experiments showed that aplidine exists as
      two isomers. A stability-indicating HPLC assay was developed. Solubility testing
      showed that aplidine exhibits very poor aqueous solubility. Because solubilized
      aplidine showed substantial degradation under heat and light stress testing
      conditions, it was decided to develop a lyophilized dosage form. Freeze-drying
      was carried out with a 500 micrograms/mL solution of aplidine in 40% (v/v) tert
      butanol in Water for Injection (WfI) containing 25 mg/mL D-mannitol as a bulking
      agent. Differential scanning calorimetry was applied to determine the optimal
      freeze-drying cycle parameters. The prototype, containing 500 micrograms aplidine
      and 25 mg D-mannitol per vial, was found to be the optimal formulation in terms
      of solubility, length of lyophilization cycle, and dosage requirements in the
      forthcoming Phase I clinical studies. Quality control of the freeze-dried
      formulation demonstrates that the manufacturing process does not affect the
      integrity of aplidine. The optimal reconstitution solution was found to be
      15/15/70% (v/v/v) Cremophor EL/ethanol/WfI (CEW). Both reconstituted product and
      dilutions of the reconstituted product with normal saline (up to 1:100 v/v)
      appeared to be stable for at least 24 hours after preparation. Shelf-life data,
      available thus far, show that the lyophilized formulation is stable for at least
      1 year when stored at +2-8 degrees C in the dark.

PMID- 10927912
TI  - beta-Propiolactone: viral inactivation in vaccines and plasma products.

PMID- 10927913
TI  - Origin, result and measurement of USP "essentially free" inspection for visible
      contaminating particles.
AB  - The efficient mass production of pharmaceuticals requires scientifically
      replicable measurements. The measurements, in turn, must be capable of
      description in words and terms that can be universally understood and applied
      beyond national, corporate, or measurement laboratory boundaries. A notable
      present exception has been the required evaluation of visible particle
      contamination in injectable products. Beginning in USP23 <788> (1) and continuing
      in USP 24 there is official recognition that the results of the nondestructive
      inspection for "visible" particles cannot be described in simple terms. Although
      the call for injectable products to be free of any visible particle contamination
      has been repeated, variability in the results of the nondestructive inspection
      for contaminating particles has been officially recognized. This recognition is
      expressed in one sentence, "Injectable solutions, including solutions constituted
      from sterile solids intended for parenteral use, should be essentially free from
      particles that can be observed on visual inspection." This phrasing describes a
      probabilistic contaminating particle inspection result. Methodology with which to
      evaluate the effectiveness of the probabilistic manual, semi- or fully-automated
      inspection for contaminating particles in sealed containers has been well tested
      for the last 21 years. This paper provides a brief, nonmathematical review of the
      core concepts that are used.

PMID- 10927914
TI  - Approaches to reducing toxicity of parenteral anticancer drug formulations using
      cyclodextrins.
AB  - Mitomycin C (MMC) is a clinically useful anticancer drug which can cause severe
      dermatological problems upon injection. It can cause delayed erythema and/or
      ulceration occurring either at or distant from the injection site for weeks or
      even months after administration. In an attempt to reduce the skin necrosis,
      complexation of MMC with cyclodextrins was studied in order to help increase
      patient compliance and acceptance. The complexation of MMC with 2
      Hydroxypropylbetacyclodextrin (HPBCD) in the presence and absence of mannitol was
      studied and it was found that the mannitol present in the commercial formulation
      caused an increase in the binding of MMC to HPBCD. Isotonicity adjustment of
      hypotonic MMC formulations by the addition of normal saline did not change the
      degree of complexation with MMC. The complexed formulations were then tested to
      determine their antitumor efficacy using the B-16 melanoma cell model. No
      difference in antitumor activity between the complexed and uncomplexed MMC
      formulations was observed. Different MMC formulations were tested for their
      potential to produce skin irritation and/or toxicity using intradermal injections
      in a BALB/c mouse model in order to find the most suitable formulation. The skin
      ulceration studies indicated that there were no significant differences between
      the isotonic MMC solution and isotonic formulations of MMC complexed with HPBCD.

PMID- 10927916
TI  - Practicalities of setting acceptance criteria for media fill trials.

PMID- 10927915
TI  - Mixed micelle proliposomes for preparation of liposomes containing amphotericin
      B, in-vitro and ex-vivo studies.
AB  - The aim of this work was to produce a form of injectable liposomes containing
      amphotericin B derived from mixed micelle proliposomes. Mixed micelles were
      derived from a mixture of lecithin/sodium cholate in aqueous media. The
      solubility of amphotericin B in proliposomes was studied as a function of lipid
      composition (total lipid concentration, molar ratio of lecithin/sodium cholate),
      and the dispersion media (pH, ionic strength, presence or absence of human serum
      albumin), and the temperature. The data show that micelle-->liposome
      transformation occurs during the dilution of proliposomes containing amphotericin
      B. These transformations could be followed via transmission electron microscopy
      (TEM). Data related to dilution of proliposomes as well, show that under no
      circumstance there occurs any precipitation that might be assigned to the
      decreased solubility of amphotericin B. These indicate that the incorporated drug
      also participates during the transformation of the proliposomes into liposomes.
      It is thus concluded that mixed micelle proliposomes are prime candidates for the
      production of a form of injectable amphotericin B in liposomes.

PMID- 10927917
TI  - Risk and the economics of regulatory compliance.

PMID- 10927918
TI  - Disinfection with flash lamps.
AB  - The analysis of published and new data on a pulsed disinfection is presented. It
      allows the conclusion that the pulsed disinfection mechanism includes both
      germicidal action of UVC light and a rupture of bacteria due to thermal stress,
      caused primarily by all UV components of the light pulse. The role of
      simultaneous cooling and heating of bacteria during a flash lamp pulse has been
      estimated and a direct detection of such a mechanism is proposed. It is suggested
      that an optimum pulsed light source for disinfection must have as much percentile
      content of a broad UV spectrum and a high peak power as is technically justified.
      Two new applications for pharmaceutics and medicine are suggested.

PMID- 10927919
TI  - [Basic trends in State regulation of public health development in the Russian
      Federation for the years 2000-2010].

PMID- 10927920
TI  - [Health status and problems of medical care of public health personnel].
AB  - Presents the data characterizing health status, conditions of life, and life
      style of medical workers in comparison with other population groups. The health
      status of medical workers with regard to many parameters is worse, and they
      experience real difficulties in correction of abnormalities; many of their
      problems are due to poor material status of workers engaged in health service.

PMID- 10927921
TI  - [Demographic processes and dynamics of public health in the Irkutsk region in the
      90-ies].
AB  - The general population regularities and regional features in the formation of
      levels, structure, and tendencies of changes in the demographic characteristics
      and population health in Russia in the 1990's have been studied as exemplified by
      the Irkutsk region. The phenomena and processes observed during this period
      reflect a high degree of ecosocial unsuccessful. The expected social consequences
      of the crisis are evaluated for the nearest and remote future.

PMID- 10927922
TI  - [Structural effectiveness of the therapeutic-preventive care in the 90-ies].
AB  - Structural efficiency of treatment-and-prophylactic care rendered to the
      population of the Russian Federation in the nineties is analyzed. The author
      emphasizes that reformation processes sufficiently well described theoretically
      and reflected in the "Concept of Development of Public Health and Medical Science
      in the Russian Federation" (1997) are realized slowly or absent at all, and the
      structural efficiency of treatment-and-prophylaxis in general is lower than
      expected. Priority trends in structural and functional transformations are
      presented.

PMID- 10927923
TI  - [Attitude of population and physicians to the organization of medical care in a
      city].
AB  - The authors analyze the population self-estimations of the health status and
      opinions on the quality of services rendered at local health centers, attitude to
      medical care, and suggestions on improvement of medical service organization.
      Analysis of interviews with physicians showed their attitude to transfer from
      state public health to medical services with different types of property and
      their opinions on modern situation in public health management. The priority
      problems of public health and potentialities of improving the activities of
      treatment and prophylactic institutions of the city and the quality of services
      rendered to the population have been identified.

PMID- 10927925
TI  - [Several aspects of insurance of professional liability of medical workers].

PMID- 10927924
TI  - [Distribution of resources for rendering medical care to cancer patients in
      hospices].
AB  - Creation of a system of palliative care in the Russian Federation is a pressing
      problem of public health, which at present is going through the first stage of
      development. According to WHO estimations, at least 75% cancer patients need
      palliative care. The system of medical care to cancer patients functioning in
      countries with well-developed economy (United Kingdom, USA, Canada, Australia)
      intends equal distribution of resources between radical treatment and palliative
      care (including analgesia) and reflects the actual requirements of patients. The
      scope of care should be extended from symptomatic treatment to comprehensive
      (medical, psychological, social, and spiritual) care of patients and their
      families.

PMID- 10927926
TI  - [Main Republican Pediatric Rehabilitation Center].

PMID- 10927927
TI  - [Control of resource use at the level of municipal public health].

PMID- 10927928
TI  - [Main trends of research in dissertations on the specialty 14.00.33 "Social
      Hygiene and Public Health Organization" approved by the Higher Attestation
      Committee of Russia in 1999].

PMID- 10927929
TI  - Role of interleukin-8 activity and phenotype in the pathogenesis of antral
      gastritis associated with Helicobacter pylori.

PMID- 10927930
TI  - Pathogenic implications of interleukin-8 activity and bacterial phenotype in
      antral gastritis associated with Helicobacter pylori.
AB  - OBJECTIVE: Helicobacter pylori (Hp) infection is characterized by an intense
      inflammatory infiltrate in the gastric mucosa, which is chemoattracted by
      different cytokines. Interleukin-8 (IL-8) seems to play an important role in the
      recruitment of circulating neutrophils, and modulation of IL-8 secretion seems to
      be a strain marker. This study was designed to examine IL-8 concentrations in the
      gastric mucosa and their relationship with H. pylori phenotype and histologic
      findings. METHODS: Gastric biopsies were obtained from the antrum and corpus in
      106 patients (69 Hp-positive and 37 Hp-negative). IL-8 levels in the gastric
      mucosa were analyzed by ELISA and Hp phenotype was determined with a western blot
      test. RESULTS: 75% of H. pylori strains were CagA+ and 54.2% were VacA+. The
      Houston classification was used for histologic findings. No association between
      gastric atrophy or intestinal metaplasia and Hp phenotype was found. The highest
      IL-8 levels were found in CagA+ infected gastric mucosa, but the difference with
      respect to infection by a VacA+ strain was not statistically significant. IL-8
      levels were highest when neutrophils were the predominant cell in the gastric
      inflammatory infiltrate (p < 0.05). IL-8 levels were higher in patients with
      atrophic gastritis than in patients with nonatrophic gastritis (p < 0.05).
      CONCLUSIONS: In patients with H. pylori infection, IL-8 levels are higher than in
      Hp-negative patients regardless of Hp phenotype. There is an association between
      IL-8 and a neutrophilic infiltrate. Perpetuation of a chronic infiltrate could
      lead to more severe lesions such as atrophic gastritis or intestinal metaplasia,
      as deduced from the IL-8 levels found in these types of lesion.

PMID- 10927931
TI  - Survival of cancer of the pancreas. Bases for new strategies in diagnosis and
      therapy.
AB  - OBJECTIVE: The ominous prognosis of pancreatic carcinoma (PC) has led to a
      nihilistic attitude among physicians, and to the need to develop better tools for
      diagnosis, staging and treatment. The aim of this study was to analyze a series
      of patients with PC in order to determine stage-related survival, and to try to
      improve diagnostic and therapeutic strategies. METHODS: This was a retrospective
      study of 167 patients diagnosed from 1987 to 1993. The diagnosis was based on
      cytological pathology findings or on a clinical course compatible with PC. TNM
      stage and survival were calculated. We also analyzed age, sex, time elapsed until
      diagnosis, diagnostic tests, size and location, cytologic pathology confirmation,
      number of patients undergoing surgery, and procedures used. RESULTS: Age: 67 +/-
      12 years, 82 men and 85 women. Time elapsed until diagnosis: 3 +/- 15.7 months.
      Pathologic diagnosis: 74.8%. LOCATION: head 75%, body 13.9%, tail 7.2%, diffuse
      2.4%, not reported 1.2%. Size: 4.6 +/- 2 cm. TNM staging: stage I 13%; stage II
      25%; stage III 20%; stage IV 42%. Stage-related survival: stage I 14 months;
      stage II 6 months; stage III 4 months; stage IV 1 month. Total survival: 3
      months. Surgery was done in 66.5% and resection in 10%; curative surgery in 6.5%;
      bypass in 81% and diagnostic laparotomy in 9%. In 55% of the patients surgery
      revealed a higher stage of disease than had been diagnosed preoperatively.
      Postoperative mortality was 18%. Survival at 1 and 5 years after curative surgery
      was 80% and 20%, respectively. CONCLUSIONS: Diagnosis was made at a late stage in
      many patients. Few patients were candidates for radical surgery. Early diagnosis,
      preoperative staging and postoperative management should be improved in these
      patients, and surgery should be associated with complementary chemotherapy and/or
      radiotherapy.

PMID- 10927932
TI  - Perforated colonic cancer. Evolution and prognosis.
AB  - OBJECTIVE: The purpose of this study was to determine whether patients with
      perforating colonic cancer, among patients who need emergency surgery, should be
      considered to comprise a group with a worse prognosis. METHODS: We
      retrospectively revised the clinical records for 91 cases of emergency primary
      resection for carcinoma of the colon, of which 22 were perforating (4 Dukes A, 10
      Dukes B and 8 Dukes C) and 69 were obstructive (3 Dukes A, 30 Dukes B and 36
      Dukes C). For purposes of comparison we also analyzed a synchronous series of 112
      patients who underwent elective surgery. RESULTS: There were no recurrences or
      deaths among the 7 patients with Dukes A disease (follow-up from 6 to 90 months),
      so these patients were excluded. In the 84 remaining emergency patients, 38
      showed progression of the disease (13 local recurrence, 17 liver metastases, 4
      lung, 3 peritoneal and 1 bone metastases). There were 26 deaths (6 patients with
      perforating and 20 with obstructive disease). There was no significant difference
      in survival or disease progression between patients with perforating and
      obstructive disease. CONCLUSIONS: These results do not support the classical view
      of considering perforating cancer as a type with an especially ominous prognosis
      among patients who require emergency surgery.

PMID- 10927933
TI  - Economic evaluation of colorectal cancer screening with fecal occult blood
      detection.
AB  - OBJECTIVE: To analyze the cost/benefit (CBA), cost/effectiveness (CEA) and
      cost/utility (CUA) of colorectal cancer (CC) screening through the detection of
      fecal occult blood (FOB). METHODS: A retrospective 10-year study was carried out
      in primary care hospitals to observe the evolution of CC in the study zone;
      subsequently, CC screening with FOB detection was done, and the entire population
      aged 50 to 75 years living in the Casas Ibanez Health Zone was invited to take
      part. When the results had been evaluated, the screening program was evaluated in
      economic terms to determine CBA and to compare screening costs (option A) with
      the cost of allowing CC to develop without intervention (doing nothing),
      according to the previous retrospective study. The CEA calculated the cost of
      each cancer found in an asymptomatic stage, and the CUA calculated the cost of
      each year adjusted to quality of life (QUALY) for both options. RESULTS: The CBA
      showed that screening for CC with FOB detection (option A) produced a savings of
      2,001,067 Spanish pesetas (USD15,310) in comparison with option B (doing
      nothing). The CEA showed that each cancer detected by screening at an
      asymptomatic stage cost 806,025 pesetas (USD6,167). The CUA showed that each
      QUALY for men in option A cost 1,051,185 pesetas (USD8,043), whereas for option B
      each QUALY would cost 4,220,315 pesetas (USD32,290). For women, each QUALY cost
      564,795 pesetas (USD4,321.31) in option A and 2,413,834 pesetas (USD18,469) in
      option B. CONCLUSIONS: Our economic evaluation demonstrates that the
      cost/benefit, cost/effectiveness and cost/utility ratios for CC screening through
      FOB detection with the Hemoccult test are better than for the alternative of
      doing nothing.

PMID- 10927934
TI  - [Quality of life. Can it really be measured?].

PMID- 10927935
TI  - [Lower gastrointestinal hemorrhage and Klippel-Trenaunay syndrome].

PMID- 10927936
TI  - [Intestinal invagination secondary to jejunal lipoma: a new case diagnosed with
      ultrasonography].

PMID- 10927937
TI  - [Amebiasis and intestinal inflammatory disease].

PMID- 10927938
TI  - [Megawirsung and bile duct dilatation caused by pancreatic cancer].

PMID- 10927939
TI  - Lessons from female dystrophinopathy.

PMID- 10927940
TI  - Congenital contractural arachnodactyly (Beals syndrome).
AB  - Congenital contractural arachnodactyly (CCA, Beals syndrome) is an autosomal
      dominant disorder that is phenotypically similar to Marfan syndrome. CCA is
      characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple
      congenital contractures and abnormalities of the external ears. We report here 28
      patients with CCA, in whom a wide range of phenotypic expression is observed.
      These individuals usually have abnormally formed ears, limited extension of
      fingers and toes, arachnodactyly, clinodactyly, delay of developmental milestones
      and psychomotor retardation. Limited extensions of elbows, knees and hips are not
      constant features. With time, those affected individuals experience spontaneous
      improvement of their contractures but the kyphosis, unlike the joint
      contractures, tends to be progressive. No ocular problems were found in all
      patients, but congenital heart defects were detected in 32.2% of them. Atrial
      septal defect and ventricular septal defect are common components in our
      patients. Within the only one family with two multiply affected siblings there is
      little phenotypic variation between the patients.

PMID- 10927941
TI  - Hepatobiliary involvement of Henoch-Schonlein purpura in children.
AB  - Hepatobiliary manifestation and its evolution in children with Henoch-Schonlein
      purpura (HSP) had been scarcely reported. Over a ten-year period between June
      1988 and November 1998, medical charts of 225 children with the diagnosis of HSP
      encountered at Chang Gung Children's Hospital were reviewed. Those with the
      evidence of hepatobiliary involvement were enrolled in the study. The patients
      with hepatobiliary involvement were defined by having an elevated serum alanine
      transaminase (ALT) or gamma-glutamyl transferase (GGT), and the presence of
      abnormal sonographic findings involving liver, biliary system, and gallbladder.
      The patients included 9 boys and 11 girls with range of age from 3 to 11 years.
      The mean age of these patients was 6.5 +/- 3.7 years. Preceding upper respiratory
      tract infection was common in these patients (35%). The main clinical
      manifestation were distinct from typical abdominal symptoms of HSP, and included
      right upper quadrant pain (80%), nausea (45%), lethargy (20%), and vomiting
      (15%). Elevated serum ALT was noted in 15 cases (75%) and GGT in 6 cases (30%).
      Abdominal ultrasonography revealed hepatomegaly (15/20, 75%), and gallbladder
      wall thickening (5/20, 25%). No specific laboratory parameters were correlated
      with the hepatobiliary manifestation of HSP. Fourteen children (70%) received
      steroid therapy and disappearance of symptoms and sonographic resolution of
      hepatobiliary lesion was noted within 3-7 days of steroid therapy. All patients
      recovered completely except for one patient with hepatobiliary recurrence
      manifested as purpuric rash, abdominal pain, elevated GGT, and gallbladder wall
      thickening during 2-year follow-up.

PMID- 10927942
TI  - Carrier detection of Duchenne/Becker muscular dystrophy by using fluorescent
      linkage analysis in Taiwan.
AB  - The mutation analysis of Duchenne/Becker muscular dystrophy (DMD/BMD) is made
      difficult by the size and structure of the gene. The dystrophin gene deletion is
      responsible for 45-58% of DMD/BMD cases in Taiwan. For the others, who have no
      deletions, carrier detection was performed by DNA linkage analysis. To determine
      frequencies of each allele and heterozygosity of each short tandem repeats (STR)
      marker, we analyzed 50 unrelated Taiwanese males and 50 unrelated Taiwanese
      females unaffected by DMD/BMD using ten fluorescently labeled intragenic markers
      (these ten being located in 5' terminus, intron 1, 44, 45, 48, 49, 50, 55-57 and
      3' untranslated region of the human dystrophin gene). The predicted
      heterozygosity frequency is 46.7-88.3% in our study population and these STR
      markers are quite informative for linkage analysis. Using these ten intragenic
      STR markers, we analyzed 14 DMD/BMD families with 62 family members for carrier
      detection. Our retrospective study of DMD/BMD families highlights the informative
      power of STR haplotyping. In summary, STR analysis using (CA)n repeats within the
      human dystrophin gene is well suited for routine use in clinical laboratories
      engaged in linkage studies for carrier detection and prenatal diagnosis in
      DMD/BMD families.

PMID- 10927943
TI  - Chronic lung disease in extremely low birth weight infants: a two-year
      retrospective analysis.
AB  - To determine the incidence and classification of chronic lung disease (CLD) in
      extremely low birth weight (ELBW) infants, a 2-year retrospective analysis was
      performed. From January 1997 to December 1998, 117 infants weighing less than
      1000 g were enrolled. The survival rate beyond 28 days was 60.7% (71/117). CLD
      was defined as a supplemental oxygen requirement at 28 days of age, with symptoms
      of persistent respiratory distress and chest radiograph showing characteristic
      appearance. In addition to the common finding of CLD, infants with
      bronchopulmonary dysplasia (BPD) had history of respiratory distress syndrome
      (RDS), infants with Wilson-Mikity syndrome (WMS) had no RDS but had early
      appearance of bubbly lung on chest x-ray, and infants with chronic pulmonary
      insufficiency of prematurity (CPIP) had only hazy appearance on chest x-ray. The
      incidence of CLD in infants who survived beyond 28 days was 50.7% (36/71). Among
      the 36 infants with CLD, 17 (47%) had BPD, 4 (11%) had WMS and 15 (42%) had CPIP.
      The median (min, max) days of mechanical ventilation were 45 (9, 112), 45.5 (45,
      50) and 7.5 (0, 40) days in BPD, WMS and CPIP groups, respectively. The median
      (min, max) days of oxygen requirement were 73 (28, 120), 149 (70, 211) and 52.5
      (38, 90) days, respectively. The infants still requiring oxygen at post
      conceptional age of 36 weeks are significantly more in BPD (14 (82.4%)) and in
      WMS (4 (100%)) than in CPIP (3 (20%)). Two (1 BPD, 1 WMS) were discharged and
      received oxygen therapy at home. Four infants with BPD died of respiratory
      failure. CLD includes a wide range of conditions, from BPD or WMS with severe
      respiratory morbidity and mortality to no residual problems. Such information is
      important for design of appropriate strategies to prevent CLD.

PMID- 10927944
TI  - Levamisole in steroid-sensitive nephrotic syndrome children with steroid
      dependency and/or frequent relapses.
AB  - The study is to evaluate the effect of levamisole on steroid-sensitive nephrotic
      syndrome (SSNS) children with multiple relapses, from October 1996 through
      December 1998, we prospectively recruited 27 SSNS children. Eight children had
      minimal change nephrotic syndrome and nine had mesangial nephropathy proven by
      renal biopsy. The other 10 children had normal renal function and no secondary
      cause of nephrotic syndrome (NS). Nine were frequent relapsers (FR), (> 4 attack
      per year), nine were steroid-dependent (SD), and another nine were both FR and
      SD. The dosage of levamisole given was 2 to 3 mg/kg daily or every other day,
      depending on the patients' response. All were followed regularly at outpatient
      department. Follow-up items included a routine urinalysis every month, complete
      blood count (CBC) every 3 months and BUN/Cr, AST/ALT every 6 months. After 6 to
      24 (mean 12.2) months of follow-up, the frequency of relapse (FoR) decreased
      (5.74 +/- 3.24 vs 1.91 +/- 2.0/year p < 0.05). Seven (26%) had no relapse at all.
      Nine (33.3%) had less than 1/3 the FoR; four (14.8%) had 1/3 to 1/2 the FoR; and
      seven (26%) still had more than 1/2 FoR as before levamisole. The oral
      prednisolone dosage also decreased (0.62 +/- 0.42 vs 0.21 +/- 0.35 mg/kg/day, p <
      0.05). The levamisole response was independent of the age of NS onset, the
      interval between NS onset and initiation of levamisole, previous number of
      relapse, the FoR, and previous use of cytotoxic drug. There were 7 episodes of
      leukopenia, which returned to normal after discontinuing levamisole for 1 to 2
      weeks in 4 patients. Two (7.5%) had reversible leukopenia for more than 4 weeks.
      No abnormal BUN/Cr, or ALT/AST levels were noted during follow-up. Levamisole is
      an effective and safe drug for children who have SSNS with FR and/or SD. Two
      thirds of patients obtain satisfactory control. The dosage can be 2 to 3 mg/kg
      daily or every other day. The most common side effect is transient leukopenia.

PMID- 10927945
TI  - Midterm results of aortic valve reconstruction for congenital aortic stenosis
      with or without regurgitation.
AB  - Aortic valve is often replaced if valvular stenosis fails to be balloon dilated.
      Aortic valve reconstruction was performed on 4 patients from August 1993 to 1999.
      Their ages ranged from 1 month to 15 years (mean 8.3 years). Unicuspid aortic
      valve was present in three of them and bicuspid in the other one. Two patients
      were associated with a patent arterial duct, one aortic regurgitation, and one
      pulmonary stenosis. Commissurotomy was done in three of them to transform the
      aortic valve into tricuspid except one, in whom bicuspid valve was preserved. In
      one case with unicuspid aortic valve, a piece of tanned autologous pericardium
      was used to augment one myxomatous and retracted leaflet. The sinus of Valsalva
      was molded together with a bulging shape of its aortic leaflet. All four were
      weaned from cardiopulmonary bypass smoothly. Transesophageal echocardiography in
      one case prompted rebypass to decrease the degree of regurgitation from moderate
      to mild by further shaping of the leaflet and sinus of Valsalva. In one patient
      chylopericardium was complicated and subsided in 5 days after conservative
      treatment. All patients were doing well on follow up at 56.8 +/- 34.4 months
      after surgery, with trivial to mild systolic pressure gradient (20 +/- 26 mmHg;
      preoperatively: 88 +/- 36 mmHg) and mild regurgitation. Aortic valve
      reconstruction is feasible in the setting of congenital aortic stenosis in our
      limited experience; repair instead of replacement is recommended even when
      regurgitation is present.

PMID- 10927946
TI  - Secondary erythrocytosis in distal renal tubular acidosis: report of one case.
AB  - The wide spectrum of distal renal tubular acidosis (RTA) has been reported.
      Children with distal RTA can present with failure to thrive, gastrointestinal
      symptoms, nephrocalcinosis, and renal failure, etc. So far, secondary
      erythrocytosis in pediatric patients with distal RTA has not been reported. Here
      we report a case of distal RTA with failure to thrive and nephrocalcinosis
      accompanied by secondary erythrocytosis in a 3-year-old boy. He has been followed
      up for 2 years and is under treatment with NaHCO3 and potassium citrate. The
      treatment contributes to the improvement of metabolic acidosis and his growth.
      There is normal renal function and constant erythrocytosis during the follow-up
      period. Further studies are needed to clarify the relationship between
      erythrocytosis and distal RTA.

PMID- 10927947
TI  - Segmental dilatation of the ileum as an unusual cause of gastrointestinal
      bleeding: report of one case.
AB  - We report a case of segmental dilatation of the ileum in a 10-month-old male
      infant. Intermittent loose black-colored stool passage and normocytic anemia were
      noted at the initial visits to our hospital. There was no symptom or sign of
      intestinal obstruction such as abdominal distention or vomiting. On physical
      examination, he was found to be pale but his abdomen was soft and flat. Digital
      examination revealed brownish stool tinged with black-colored oil-like stool but
      no polyp. Laboratory studies excluded coagulopathy, hemolytic anemia and lead
      poisoning. During hospitalization, he was treated with nothing per mouth,
      intravascular fluids, ranitidine, and transfusion of packed red blood cells. All
      examinations including panendoscopy, Technetium-99m (99mTc)-pertechnetate
      Meckel's diverticulum scan, and double contrast colon series revealed no organic
      lesion except that 99mTc-red blood cell bleeding scans showed abnormal bleeding
      in the small intestine. Because of his persistent gastrointestinal bleeding with
      unknown cause, we did an exploratory laparotomy when the patient was 13 months
      old and idiopathic segmental dilatation of the ileum was confirmed. The dilated
      segment is supposed to be idiopathic because of histologically proven normal
      muscle layers without ectopic tissue. This case suggests that segmental
      dilatation of the ileum can only present as gastrointestinal bleeding without
      intestinal obstruction.

PMID- 10927948
TI  - Pyogenic liver abscess caused by Pseudomonas aeruginosa in a previously healthy
      child: report of one case.
AB  - Pyogenic liver abscess (PLA), a very uncommon liver disease in the normal
      pediatric group is often associated with immunocompromised conditions.
      Pseudomonas aeruginosa has long been regarded as a relatively rare pathogen of
      PLA, especially in patients without underlying problems. A previously healthy one
      year-and-seven-month-old boy who had symptoms of fever, vomiting and diarrhea got
      a liver abscess at right hepatic lobe which was confirmed by abdominal ultrasound
      and computed tomography (CT) diagnoses. Ultrasound-guided percutaneous aspiration
      of liver abscess was done soon after the confirmation. The culture result of
      aspirate grew P. aeruginosa. The patient received a 4-week course of adequate
      antibiotics treatment after the aforementioned aspiration procedure. In addition,
      a series of ultrasounds were performed to follow the resolution of abscess during
      the treatment period. The immune function tests of the patient were within normal
      ranges. Finally, the lesion resolved completely without leaving any complication.

PMID- 10927949
TI  - Papillary cystic neoplasm of the pancreas in children: report of three cases.
AB  - Papillary cystic neoplasm of the pancreas is very rare in children. There were
      only 35 pediatric cases reported in the literature. We herein three children who
      had papillary cystic neoplasm of pancreas. They were female teenagers, and were
      pathologically diagnosed. The major presenting symptoms were abdominal pain and
      abdominal mass. Serum tumor markers of these patients showed normal results. A CT
      scan of these patients showed that this tumor was of pancreatic origin. These 3
      tumors were localized to head, body, and tail, respectively. The mean maximal
      diameter of these tumors was 11.3 +/- 3 cm. Sonography and CT examination showed
      that the tumor was a heterogeneous mass with solid and cystic components.
      Angiography of this tumor showed a hypervascular mass with blood supply mainly
      from pancreatic branch of splenic artery. They all underwent tumor resection. All
      tumors contained some degree of internal hemorrhage or cystic degeneration and
      all were well encapsulated. Histologically, tumor cells generally showed solid
      and pseudopapillary growth around the fibrovascular stalks. No metastasis,
      mortality or recurrence was noted during follow-ups. In conclusion, CT scan helps
      to make a prospective diagnosis of papillary cystic neoplasm of pancreas. Our
      study confirmed that a papillary neoplasm of the pancreas is a low-grade
      malignant tumor. Surgical resection of the tumor is the mainstay of effective
      management.

PMID- 10927950
TI  - Developmental biology: frontiers for clinical genetics.

PMID- 10927951
TI  - Pediatric upper gastrointestinal endoscopy: state of the art.
AB  - Upper gastrointestinal (GI) endoscopy has become a routine procedure in
      pediatrics. It has been proven safe, highly informative and cost effective when
      used in the outpatient setting by experienced endoscopists. This review
      summarizes the experience in pediatric upper GI endoscopy over the last 30 years.
      It is focused on safety issues, indications, choice of sedation, techniques of
      the procedure itself as well as interpretation of endoscopic appearance of the
      most common diseases of the upper GI tract in children. Details of advanced
      procedures such as endoscopic retrograde cholangiopancreatography (ERCP),
      sclerotherapy and ligation of esophageal varices and foreign body removal are
      discussed as well.

PMID- 10927952
TI  - Application of Fluid-Attenuated Inversion Recovery pulse sequence in children
      with tuberous sclerosis.
AB  - To evaluate the application of Fluid-Attenuated Inversion Recovery (FLAIR) pulse
      sequence to increase the sensitivity of detecting tubers in tuberous sclerosis
      patients compared with fast spin-echo T2-weighted (FSET2W) image, we obtained 12
      magnetic resonance (MR) images in 10 patients (mean age = 57.7 months old). Among
      the 12 examinations, 114 cortical and 128 subcortical tubers were revealed on the
      FLAIR images, whereas 54 and 72 tubers were found respectively on the FSET2W
      images. This may be due to the FLAIR pulse sequences remarkably attenuated CSF
      signals in comparison with the FSET2W images. However, FSET2W image delineated
      more subependymal nodules than FLAIR imaging did. Gd-DTPA enhanced T1W image is
      the most suitable pulse sequence to detect giant cell astrocytoma near the
      foramen of Monro. The results in cases of infants and little children were
      similar.

PMID- 10927953
TI  - Comparison of intensive care of injured children between pediatric-based and non
      pediatric-based intensive care units in a university hospital in Taiwan.
AB  - Intensive care management of the injured child requires a multidisciplinary
      approach and meticulous attention to detail. However, the overwhelming majority
      of injured children are cared for by surgeons in surgical intensive care units
      (ICU) that see both adult and pediatric patients. There have been no previous
      reports of studies comparing the outcome in surgical ICUs (SICU) dealing with
      patients of all ages versus the outcome in pediatric ICUs (PICU). This study
      sought to determine differences in the outcome of pediatric intensive care
      between the SICU and PICU of our hospital. From Jan. 1989 to Aug. 1995, 118
      children (68 boys and 50 girls), with an average age of 9.19 years (range: 3
      months to 16 years), were admitted to our SICU. During the same period, 65
      children (42 boys and 23 girls), with an average age of 5.04 years (range: 2
      months to 16 years), were admitted to our PICU. Most of these patients received
      surgical intervention and were exclusively under surgeons' management. The
      decision to admit patient to the SICU or PICU was made by surgeon based on the
      availability of ICU beds. Pediatric risk of mortality (PRISM) score was used as a
      scoring system to assess disease severity in children. The most common cause for
      admission in both ICUs was traffic accidents. The average hospitalization
      duration in the SICU was 4.06 days (range 1 day to 23 days) and 3.34 days (range
      1 day to 17 days) in the PICU. The average PRISM score was 7.87 (range 0-41) in
      the SICU and 6.48 (range 0-35) in the PICU. The overall mortality rate in the
      SICU was 12.7% (15/118) and 7.7% (5/65) in the PICU. There was a significant
      difference in patients' age and operative status but no significant difference in
      admission duration, PRISM score, and mortality rate between the SICU and PICU
      groups. The regression coefficients of the selected predictor variables and the
      impact on outcome showed one more score of PRISM would increase 1.5 fold of risk
      to become poor outcome while operation had lower risk (0.1 fold) to develop poor
      outcome. In conclusion, disease diversity and severity were similar among PICU
      and pediatric SICU patients in this study. The outcome was better in PICU
      patients although the difference was not statistically significant. The PRISM
      score is a useful measure to predict poor outcome in ICU patients after
      adjustment with confounders.

PMID- 10927954
TI  - Analysis of anthropometric growth trends and prevalence of abnormal body status
      in Tainan elementary-school children.
AB  - Objectives of this study were to examine the prevalence of over/underweight or
      obesity in Chinese children and investigate the trend of anthropometric change
      through the years. Cross-sectional measurements on randomly selected 6,373 Tainan
      elementary-school children were conducted in 1997. Anthropometric parameters such
      as height, weight, body mass index (BMI), triceps skinfold thickness (TSF), mid
      arm circumference (MAC) and body-fat percentage (%FAT) were measured. Girls and
      boys had an average of 4.8 cm and 5.1 cm, or 3.7% and 3.9% increase in height,
      and 5.5 kg, 6.2 kg, or 19.9% and 22.2% increase in weight when compared to data
      of nationwide survey in 1986-88. If the height and weight were compared to the
      data of nationwide survey in 1993-1996, Tainan girls and boys would have similar
      height but have averaged 3.4% and 4.7% heavier weight. Mean BMI reached 19.4
      kg/m2 for girls and 19.6 kg/m2 for boys of age 12 to 13. Mean %FAT of girls was
      24.3% and of boys was 23.7%. When using weight-for-length index (WLI) larger than
      1.2, mean weight exceeding 120% of age-and-sex specific mean weight, %FAT
      exceeding 30% to evaluate prevalence of obesity, results would be 42.1%, 17% and
      22.0% respectively. In conclusion, both sexes had faster growth in weight than in
      height in recent 10 years. Boys had significantly higher weight, WLI, BMI, MAC
      than girls, while girls had significantly higher TSF and %FAT than boys.
      Prevalence of obesity is highly method-dependent. Appropriate index and cutoff
      values need to be developed.

PMID- 10927955
TI  - A survey of congenital heart disease in patients with oral clefts.
AB  - The purpose of this study is to determine the prevalence of congenital heart
      disease in patients with cleft lip and/or palate. We undertook a retrospective
      study of 1148 cases, age < 15 years old, with cleft lip and/or palate from
      January 1991 to December 1998, of which congenital heart disease was associated
      in 62 patients. The overall prevalence of congenital heart disease in patients
      with clefts was 5.4%. Of the 62 patients, there were 38 boys and 24 girls. We
      classified clefts into one of three categories; group 1: cleft lip alone; group
      2: cleft lip and palate; group 3: cleft palate alone. The cleft lip and palate
      (group 2) was present in the majority (27 of 62; 44%) of patients with congenital
      heart disease. Twenty-five patients (40%) had cleft palate, and ten patients
      (16%) had cleft lip. Isolated atrial septal defect and ventricular septal defect
      are the two common congenital defects, which presented 23% and 21% of patients,
      respectively. Apart from congenital heart disease and cleft lip or palate, 56%
      (35 of 62 patients) and additional abnormalities. Central nervous system and
      skeletal malformations were the most common associated abnormalities. In our
      study, congenital heart disease was more common in patients of group 2 and group
      3 than of group 1. In addition, there was a significantly greater proportion of
      patients associated with other systemic anomalies in groups 2 and 3 than in group
      1 (chi-square chi 2 = 7.535, p = 0.023), but no significant difference was noted
      between group 2 and group 3. We recommend that it would be appropriate for all
      cleft patients to receive a routine examination for associated anomalies by a
      pediatrician. With the widespread use of echocardiography and/or brain
      sonography, the early diagnosis and treatment of these anomalies are possible.

PMID- 10927956
TI  - Secondary hypertension in children.
AB  - Secondary hypertension is a potentially curable disease. One-hundred-and thirty
      six children was diagnosed as hypertension in the National Taiwan University
      Hospital from January 1992 to June 1998 and they were retrospectively reviewed
      and analysed for the etiological factors, presentation, and clinical outcome. The
      most common cause of hypertension was coarctation of aorta in infants and
      systemic lupus nephritis in adolescents. These children often presented symptoms
      and signs not directly related hypertension (37.5%). Twenty eight children
      (20.6%) died. The hypertension of the survival had been controlled by surgery,
      chronic hemodialysis, or medication.

PMID- 10927957
TI  - Persistent hypertransaminasemia as the presenting findings of muscular dystrophy
      in childhood.
AB  - Prolonged elevation of the serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) is often attributed to hepatic diseases. However, these
      enzymes are also present in a variety of extrahepatic tissues, including skeletal
      muscle. Five children (all boys) were referred to the pediatric department of the
      National Taiwan University Hospital because of persistent elevation of serum
      aminotransferase activities. The ages of these children were between 4 months and
      5.5 years. The neurological findings were all not remarkable. The initial ALT and
      AST values were 114-581 U/L and 183-700 U/L, respectively. Serum creatine kinase
      was checked first after 0 to 30 months follow-up and found to be markedly
      elevated (range, 10,557 U/L to 62,508 U/L). Muscle biopsies in the five cases all
      showed degenerating and regenerating myofibers with interstitial fibrosis. In
      Cases 3, 4 and 5, complete absence of dystrophin immunoreactivity was found.
      Genetic studies showed deletions in the DMD gene (exons 45-48 in case 2 and 49-50
      in case 4). This experience indicates that occult muscle diseases should be taken
      into account in patients with unexplained long-lasting hypertransaminasemia and
      therefore measurement of serum creatine kinase activity and muscle biopsy should
      be done early for the correct diagnosis of muscular dystrophy.

PMID- 10927958
TI  - Characterization of group D1 non-typhoid Salmonella isolates by serotyping and
      pulsed field gel electrophoresis.
AB  - Non-typhoid salmonella infection is not uncommon in immunocompetent patients in
      Taiwan. Bacterial factors may play an important role in the pathogenesis of such
      infections. In a previous study, Salmonella group D1 was found to have the
      tendency to cause bacteremia with a higher frequency than other serotypes. In the
      present study, we prospectively collected 94 Salmonella group D1 isolates for
      serotyping and molecular typing. Salmonella panama and Salmonella dublin seemed
      more invasive than other serotypes. Pulsed field gel electrophoresis was also
      done to characterize of Salmonella enteritidis and Salmonella dublin. PFGE type
      "a" of Salmonella dublin appeared to be more invasive than the other two PFGE
      types. All six Salmonella dublin isolates were Vi antigen negative. Further study
      using a larger number of isolates is needed to identify the tendency to invade
      blood stream of Salmonella dublin and Salmonella panama.

PMID- 10927959
TI  - EEG--a valuable tool in early diagnosis of Angelman syndrome.
AB  - Angelman Syndrome (happy puppet syndrome) is one of the genetic diseases causing
      developmental delay in children. Late diagnosis used to be the rule because of
      delayed appearance of disease markers such as craniofacial dysmorphism, ataxia,
      unprovoked laughter and seizure. However, reports have described characteristic
      EEG changes such as 2-3 Hz large amplitude slow wave paroxysms which appear early
      and are quite specific to the syndrome. With EEG aid, we made very early
      diagnosis in a 9 month-old young infant. And we would like to advocate the use of
      EEG study in cryptogenic psychomotor retardation in children.

PMID- 10927960
TI  - Kimura's disease in a teenage male: report of one case.
AB  - A 14-year-old boy gradually developed several subcutaneous masses over bilateral
      peri-auricular regions, neck, and both upper arms near the elbows over the past 2
      years. The recent development of eyelid puffiness elicited his seeking medical
      attention. Hypereosinophilic syndrome was first considered due to the markedly
      elevated blood eosinophil count without other evidence of allergy or parasite
      infestation, but the absence of organ involvement made this diagnosis
      questionable. The histopathological investigation of the subcutaneous mass in the
      upper arm showed lymph node-like tissue with markedly reactive follicular
      hyperplasia and eosinophilic abscesses associated with granulomatous
      inflammation, thus leading to the final diagnosis of Kimura's disease. Oral
      prednisolone was prescribed successfully. This illness occurs mainly in young
      oriental males. We report this case to introduce it to pediatric clinicians as an
      important differential diagnostic entity in eosinophilia-associated diseases and
      reactive lymphadenopathy.

PMID- 10927961
TI  - Development of acute lymphoblastic leukemia in a child after treatment of
      Langerhans cell histiocytosis: report of one case.
AB  - Langerhans cell histiocytosis (LCH) is a group of poorly understood disorders. To
      our knowledge, LCH is a non-malignant disorder. The association of LCH with a
      secondary neoplasm has not been well assessed, however, a few cases have been
      reported. We report a case of LCH, a localized osteolytic lesion over metaphysis
      of left femur, who was treated with local curettage and chemotherapy with
      vincristine, prednisone and 6-mercaptopurine (6-MP) for eight months from end of
      1991 to August, 1992. Six years later, she had acute lymphoblastic leukemia (ALL)
      in 1998. In review of current literature, only 5 cases of LCH, including our
      case, have preceded ALL. The possible association, a reactive process or a
      therapy-related process, between LCH and acute leukemia is still unclear at
      present and needs to be explored by more studies in the future.

PMID- 10927962
TI  - Agnathia in one of heterozygous twins.
AB  - Agnathia is a rare developmental field complex in humans with the structural
      defects limited to the craniofacial region. This rare complex can occur in
      combination with holoprosencephaly and situs inversus. Here we report on a pair
      of twins. The female infant had characteristic malformation complex of agnathia,
      while her twin brother showed normal appearance eventually. This case is the
      first reported case of isolated agnathia in twins.

PMID- 10927963
TI  - 3-hydroxy-3-methylglutaric aciduria presenting with Reye like syndrome: report of
      one case.
AB  - We report the case of a patient with 3-hydroxy-3-methylglutaric aciduria who
      presented with a repeat attack of Reye like syndrome clinically. Vomiting and
      somnolence, generalized tonic and clonic convulsions with hepatomegaly,
      hyperammonemia, liver function impairment, and mild metabolic acidosis were the
      presenting signs. 3-hydroxyisovaleric, 3-methylglutaric, 3-methylglutaconic and 3
      hydroxy-3-methylglutaric acids were detected in the urine by gas chromatography
      mass spectrometry. 3-methylglutarylcarnitine was also identified in the urine by
      fast atom bombardment and tandem mass spectrometry. Therefore, the possibility of
      metabolic disease should be considered in neonates and infants with repeat
      attacks of Reye like syndrome and a history of similarly affected siblings.

PMID- 10927964
TI  - Steroids used to desensitize penicillamine allergy in Wilson disease.
AB  - Patients with Wilson disease require life-long treatment and penicillamine is the
      drug of choice. We present a 14-year-old boy with Wilson disease who developed
      hypersensitivity reaction 2 days after starting penicillamine therapy. His
      symptoms included fever, maculopapular rash and lip edema. The allergic reaction
      disappeared when penicillamine was discontinued, but relapsed after reinstituting
      penicillamine at a lower dose. Desensitization was attempted by introducing
      steroid therapy, the dose of 0.7 mg per kilogram per day of prednisolone for 2
      days, then penicillamine was successfully tolerated. Subsequent tapering of the
      daily prednisolone dose was performed till it was discontinued one month after
      treatment began. We suggest that concomitant use of steroid and penicillamine
      should be used for the treatment of patients who develop penicillamine
      intolerance.

PMID- 10927965
TI  - Technology in medicine: ontology, epistemology, ethics and social philosophy at
      the crossroads.
AB  - In reference to the different approaches in philosophy (of medicine) of the
      nature of (medical) technology, this article introduces the topic of this special
      issue of Theoretical Medicine and Bioethics, that is, the way the different forms
      of medical technology function in everyday medical practice. The authors
      elaborate on the active role technology plays in shaping our views on disease,
      illness, and the body, whence in shaping our world.

PMID- 10927966
TI  - What diagnostic devices do: the case of blood sugar measurement.
AB  - Diagnostic devices do more than just passively register facts. They intervene in
      the situations in which they are put to use. The question addressed here is what
      this general remark may imply in specific cases. To answer this question a
      specific case is being analysed: that of the blood sugar measurement device that
      people with diabetes may use to monitor their own blood sugar levels. This device
      not only allows the patients concerned to better approach normal blood sugar
      levels, but alters what counts as normal in the first place. Using the device may
      shift people's attention away from their physical sensations towards the numbers
      measured, but it may also help them to increase their own physical self
      awareness. Self-monitoring finally (something that the devices have made
      possible) makes patients less dependent on professionals, but it requires them to
      engage in self-disciplining and binds them to the outcomes of their measurement
      activities: their own blood sugar levels.

PMID- 10927967
TI  - Managing one's body using self-management techniques: practicing autonomy.
AB  - This paper discusses some of the anthropological and philosophical features of
      the use of self-management plans by patients with a chronic disease, focusing on
      patients with asthma. Characteristics of this technologically mediated form of
      self-care are contrasted with the work of Mauss and Foucault on body techniques
      and techniques of self. The similarities and differences between self-management
      of asthma and Foucault's technologies of self highlight some of the ways in which
      self-management contributes to modifications in the definitions of patients and
      physicians. Patients, in measuring their lung function, first come to rely on
      measurements more than on felt disturbances, but next, felt disturbances become
      modified by previous measurements. Physicians, one the other hand, see their role
      changed from expert to being a participant in a joint treatment. It is argued
      that the concept of agency is more appropriate for describing the advantage of
      self-management for patients than autonomy.

PMID- 10927968
TI  - Technology and the management of trust in insurance medicine.
AB  - This article deals with the question how technology contributed to the performing
      of objective assessments of health risks and to the public trust in the insurance
      institution. Many authors have pointed to the relevance of medical or statistical
      technology with regard to the constitution of objectivity, because these
      technologies should be capable of diminishing the influence of social
      interactions--the "human element"--on the process of producing knowledge about
      health risks. However, in this article it is shown that the constitution of
      objective risk assessments and public trust cannot be seen as the product of one
      particular type of technology, but that it is the product of a socio-technical
      network, in which several heterogeneous elements become interrelated and
      interdependant. The historical reconstruction of this network also sheds a new
      light on the role of 'the human element' in the constitution of objectivity and
      trust. It shows that elements in the network which regulate the social
      interaction between the subjects involved are of no less importance to generate
      trust than technologies which tend to abstract from this interaction. In other
      words, objective and subjective elements are intertwined much more than is often
      recognized, and public trust is to a fairly large degree depends on conventions
      in social interaction.

PMID- 10927969
TI  - Multiplying obstetrics: techniques of surveillance and forms of coordination.
AB  - The article argues against the common notion of disciplinary medical traditions,
      i.e. Obstetrics, as macro-structures that quite unilinearily structure the
      practices associated with the discipline. It shows that the various existences of
      Obstetrics, their relations with practices and vice versa, the entities these
      obstetrical practices render present and related, and the ways they are connected
      to experiences, are more complex than the unilinear model suggests. What allows
      participants to go from one topos to another--from Obstetrics to practice, from
      practice to politics, from politics to experience--is not self-evidently induced
      by Obstetrics, but needs to be studied as a surprising range of passages that
      connect (or don't). Techniques and devices to supervise the delivery, to render
      present the fetus during pregnancy, and to monitoring birth, are described in
      order to show that such techniques acquire different roles in connecting and
      creating Obstetrics as a system and obstetrical practices.

PMID- 10927970
TI  - Medical informatics and the concept of disease.
AB  - This paper attempts to address the general question whether information
      technologies, as applied in the area of medicine and health care, have or are
      likely to change fundamental concepts regarding disease and health. After a short
      excursion into the domain of medical informatics I provide a brief overview of
      some of the current theories of what a disease is from a more philosophical
      perspective, i.e. the "value free" and "value laden" view of disease. Next, I
      consider at some length, whether health care informatics is currently modifying
      fundamental concepts of disease. To this question I will answer largely in the
      negative, and I will provide the sketch of some arguments from current research
      programs in medical informatics why I think this is the case. This argumentation
      is supported by a detailed account of how the disease profile for beriberi heart
      disease, used in one of the major medical informatics diagnostic programs, QMR
      (and its ancestor INTERNIST-1), was developed, and why at least this program
      essentially follows received views of traditional medicine. The one main
      exception to the conformity of this program to "received" views of a disease
      occurs when the program's designers need to fine-tune a disease definition. This
      fine-tuning is to comport with the expert's perspective on the disease, including
      his or her epistemic values, as well as the program's other resources for
      diagnosing components of a disease.

PMID- 10927971
TI  - The ethics of assessing health technologies.
AB  - Health technology assessment (HTA) consists of the systematic study of the
      consequences of the introduction or continued use of the technology in a
      particular context, with the explicit objective to arrive at a judgment of the
      value or merit of the technology. Ideally, it is aimed at assessing all aspects
      of a given technology or group of technologies, including non-technical, e.g.
      socio-ethical, aspects. However, methods for assessing socio-ethical implications
      of health technology are relatively undeveloped and few mechanisms exist to take
      action based on the results of such evaluations. Still, the examples of cochlear
      inplants (CI) and other cases illustrate that HTA is not a matter of merely
      collecting the facts about a technology. The facts must be plausible and relevant
      from a particular framework, which is not always shared by different groups. It
      is here that socio-ethical aspects are encountered. If health technology
      assessment aims to enhance the accountability of the decision making process
      regarding funding and use of health technology, it is a major challenge to
      assessors of health technologies to deal adequately with existing value
      pluralism. In this respect interactive evaluation may have something to offer.

PMID- 10927972
TI  - Ethics and cost-effectiveness can raise quality of care.

PMID- 10927973
TI  - Smoking status should be the fifth vital sign.

PMID- 10927974
TI  - Public health funding in Wisconsin.

PMID- 10927976
TI  - Clinical studies in Wisconsin: cancer research at the local level.

PMID- 10927975
TI  - A decade of improvement in areas of chronic disease. Where do we go from here?
AB  - The last decade has seen significant progress in reduction of mortality rates
      from many chronic diseases on both a state and national level. Moreover, in
      general, Wisconsin has achieved levels below the United States for mortality.
      However, as suggested by Figures 1 and 2, preventive efforts in stroke and
      prostate cancer should become high priorities in this state. Additionally, it
      will be important to monitor the stabilization of death rates due to diabetes.
      Turning Point, anti-tobacco efforts by the Tobacco Control Board and the Thomas
      T. Melvin Program, and the upcoming Minority Health Report should reveal
      additional areas for DHFS and its statewide partners to address in the arena of
      chronic disease. Programs such as the Wisconsin Diabetes Control Program and the
      Wisconsin Well Woman Program will also continue to contribute significantly to
      other community and clinical efforts to control chronic diseases.

PMID- 10927977
TI  - Chronic disease in the minority population. Setting goals to eliminate racial
      health care disparities.

PMID- 10927978
TI  - Colorectal cancer in Wisconsin: trends in mortality, prevention, and early
      detection strategies.

PMID- 10927979
TI  - Progress in cancer control in Wisconsin.
AB  - INTRODUCTION: The burden of cancer in Wisconsin is significant, with cancer
      accounting for nearly 25% of all deaths in 1997. State and national trends
      indicate a decline in overall cancer mortality since the early 1990s. This report
      reviews the progress in cancer control in Wisconsin in the past decade and
      assesses progress toward reaching the 2000 cancer objectives outlined in the
      Wisconsin Public Health Agenda. METHODS: Mortality data were abstracted from CDC
      WONDER from 1984-1997 in a manner consistent with the data presented in the
      Wisconsin Public Health Agenda. Overall cancer mortality, as well as site
      specific cancer mortality rates, was analyzed by calculating the percent change
      in the baseline period (1984-1986) versus the most recent available data (1995
      1997). RESULTS: Overall cancer mortality rates in Wisconsin decreased 1% from
      1984-1986 to 1995-1997, decreasing among those under age 65 but increasing among
      those 65 years of age and older. Rates declined in the white population, but
      increased among blacks and other races. Site-specific data indicate a 6% decrease
      in cervical cancer, an 18% decrease in breast cancer, and a 20% decrease in
      colorectal cancer occurred during this time period. Increases were seen in lung
      and prostate cancers, and in malignant melanoma. DISCUSSION: This analysis
      indicates progress in the reduction of overall cancer mortality among persons
      under age 65. Objectives for 2000 will be met in both breast and colorectal
      cancer, with some progress noted in reversing the steady increase in lung cancer
      mortality in the state.

PMID- 10927980
TI  - A cost analysis of community screening for diabetes in the central Wisconsin
      Medicare population (results from the MetaStar pilot project in Wausau).
AB  - CONTEXT: Type 2 diabetes mellitus is often undiagnosed and untreated. OBJECTIVE:
      To estimate the costs and possible savings of screening for Type 2 diabetes
      mellitus in the Wisconsin Medicare population from a population health
      perspective. DESIGN: The costs and benefits of community screening were analyzed
      using various primary and secondary data sources. Data on the community screening
      were obtained by MetaStar, collaborators at the screening site, and published
      material. Results from a Monte Carlo simulation model, developed by the CDC
      Diabetes Cost-Effectiveness Study Group, and recent developments in diabetes
      research were used to estimate the incidence levels of major complications for
      Type 2 diabetes. SETTING AND PARTICIPANTS: Medicare beneficiaries in central
      Wisconsin residing in the Wausau Hospital Service Area, which is composed of 14
      zip codes. RESULTS: Of 826 Medicare patients screened, 32 were diagnosed as
      having diabetes. If we use the same assumptions offered by the CDC Study Group,
      we find that the excess lifetime costs from screening and early treatment ($4850)
      exceed costs saved from preventing complications ($378), costing an average of
      $4471 per diabetic. However, if we alter assumptions on cardiovascular disease
      reduction risk and routine care costs, we find that screening could save an
      average of $619 per diabetic detected. CONCLUSIONS: The costs of community
      screening, using the CDC Study Group's assumptions, are greater than the costs of
      diabetes without screening in this population. However, recent evidence on
      cardiovascular disease risk and routine care costs could alter the results,
      leading to lower costs and greater benefits in the future. More research is
      necessary, particularly in the area of quality of life measures, to more
      accurately reflect the benefits of screening.

PMID- 10927981
TI  - Diabetes mortality trends in Wisconsin, 1979-1997: the increasing gap between
      whites and blacks.
AB  - Diabetes is a leading cause of morbidity and mortality in Wisconsin and the
      United States. We examined mortality trends for diabetes as an underlying cause
      of death for the years 1979-1997 for Wisconsin and the United States. Diabetes
      mortality rates in Wisconsin have increased over the past 18 years, from
      13.5/100,000 in 1979 to 16.7/100,000 in 1997. Much of this increase is
      attributable to a change in the death certificate in 1989. Blacks in Wisconsin
      have a higher rate of diabetes mortality when compared with whites, especially
      among women and persons less than 65 years of age. This disparity has increased
      markedly over the decade. Public health efforts in Wisconsin need to focus on
      reducing diabetes mortality overall and on minimizing disparities in diabetes
      mortality between whites and blacks.

PMID- 10927982
TI  - The Wisconsin Collaborative Diabetes Quality Improvement Project.
AB  - INTRODUCTION: Performance measurement is an important tool for improving the
      quality of diabetes care. In this report we describe the Wisconsin Collaborative
      Diabetes Quality Improvement Project, designed to assess the quality of diabetes
      care among 18 health care organizations in the state. METHODS: Fifteen health
      maintenance organizations, a tribal council, a health care provider, and an
      insurance corporation participated in the project. Each health care organization
      reported the percent of their diabetes population who had received selected
      measures of diabetes preventive care during the reporting year, using HEDIS
      performance indicators. RESULTS: The proportion of the population with diabetes
      receiving preventive care varied by indicator: retinal eye exam (ages > 31 years:
      55%; ages 18-75 years: 48%), annual lipid profile (58%); hemoglobin A1c (81%);
      and nephropathy screening (27%). Rates also varied among health maintenance
      organizations for each indicator, with rates varying three-fold between
      organizations for the retinal eye exam indicator (ages > 31 years). CONCLUSIONS:
      These data demonstrate considerable variability in the delivery of preventive
      services to this population with diabetes. The collaborative group involved in
      this project is currently exploring further collaborative quality improvement
      opportunities.

PMID- 10927983
TI  - Increasing prevalence of overweight among Wisconsin adults, 1989-1998.
AB  - OBJECTIVES: Overweight is an important condition that increases the risk of
      chronic diseases such as diabetes, heart disease, and cancer. We examined trends
      in overweight prevalence among Wisconsin adults from 1989 to 1998 and assessed
      progress in reaching the overweight 2000 goal for Wisconsin. METHODS: We used
      data on the self-reported height, weight, and calculated body mass index from the
      Wisconsin Behavioral Risk Factor Survey to examine overweight prevalence trends
      among Wisconsin adults. RESULTS: The prevalence of overweight has increased over
      40% during the past decade from 23% of adults in 1989, to 34% of adults in 1998.
      The increase occurred in men and women, blacks and whites, and all age groups. In
      1998, 330,000 more adults were overweight in Wisconsin, compared to 1989.
      CONCLUSION: As rates of overweight continue to increase, the incidence and
      prevalence of many chronic diseases will also increase. Effective population
      based efforts are required to reduce caloric intake and increase physical
      activity among Wisconsin adults.

PMID- 10927984
TI  - Too many treatments for Parkinson's disease: how should they be used?
AB  - Surgical ablation for Parkinson's disease was abandoned in the 1970s after
      successful clinical trials of L-DOPA and L-DOPA/decarboxylase inhibitor
      combinations and early dopamine receptor agonists were added to prolong a viable
      therapeutic window beyond 5 years. The development of newer agonists with
      variations in receptor subtype specificity and new enzyme inhibitors with
      combinations of central and peripheral effects have continued to attract
      attention as therapeutic alternatives. Treatment options are now coming full
      circle with a rebirth of stereotactic neurosurgical alternatives to a wide
      variety of pharmacologic paradigms. The authors propose a rationale for selecting
      differing treatment options within historical perspective and modern treatment
      goals using both medical and surgical alternatives.

PMID- 10927985
TI  - Falsely elevated INRs in warfarin-treated patients with the lupus anticoagulant.
AB  - The Lupus Anticoagulant (L.A.) is an antibody that prolongs the clotting time of
      in-vitro laboratory tests by binding phospholipid in the test system. Patients
      with the L.A. are at increased risk for development of venous and arterial
      thrombosis but not hemorrhage. Therefore, many patients with the L.A. are being
      treated with warfarin sodium to prevent reoccurrence of thrombosis. This oral
      anticoagulant therapy is traditionally regulated by periodic determination of the
      Prothrombin Time (PT). This test is usually unaffected by the L.A. However, we
      have recently identified a small series of patients with the L.A. in whom the PT
      is affected by the L.A. This interference is manifest as an artifactually
      increased International Normalized Ratio (INR). These patients were identified by
      failure to achieve significant correction of the PT with addition of an equal
      volume of normal plasma to the patient plasma and a Factor X level discordant
      with the PT INR Interference in determination of the PT by the L.A. was found to
      occur in 6.5% of patients identified with the L.A. by our laboratory. It is
      suggested that patients with this complication of anticoagulant therapy be
      monitored by measurement of Factor X levels rather than the PT INR. Failure to
      recognize this complication may result in inadequate anticoagulation and
      recurrent thrombosis.

PMID- 10927986
TI  - Hypertension in women.
AB  - More women than men eventually develop hypertension in the United States due to
      their higher numbers and longer longevity. The white coat hypertension is also
      more common in women. Alcohol, obesity and oral contraceptives are important
      causes of rise in blood pressure among women. On the other hand, hormone
      replacement therapy may decrease cardiovascular mortality in the postmenopausal
      woman. Women with left ventricular hypertrophy are at a greater risk of death
      than men. Fibromuscular hyperplasia and primary aldosteronism are more common as
      causes of secondary hypertension in women. Nonpharmacologic therapy, such as
      weight reduction, exercise, salt and alcohol reduction, should always be tried
      prior to medical treatment of hypertension and are very useful adjunctive
      measures in controlling hypertension. ACE inhibitors and angiotensin receptor
      blockers are contraindicated in pregnancy and should be avoided in women with
      childbearing potential. Hypertension remains a major public health problem among
      black women. Although the antihypertensive drug therapy seems to benefit white
      women the least, proportionately more of them comply with their antihypertensive
      therapy. Hypertension is the most common chronic medical condition requiring
      visits to the physicians, as well as prescription medications, in the United
      States. The epidemiology, clinical course, response to treatment and ultimate
      outcome of essential hypertension may vary with gender. More women than men
      eventually develop hypertension in the US due to their higher numbers and longer
      longevity.

PMID- 10927987
TI  - Public health strategies to reduce and prevent alcohol-related illness, injury
      and death in Wisconsin and Milwaukee County.
AB  - This paper illustrates the application of a Public Health Model toward
      understanding the nature and extent of alcohol-related problems and, in turn,
      provides examples of strategies targeted at reducing or preventing alcohol
      related illness, injury and death in Wisconsin and Milwaukee County. More
      specifically, data are provided detailing the widespread use and misuse of
      alcohol as well as the medical, behavioral and social problems associated with
      its use. Alcohol use and misuse is the third leading cause of preventable death
      behind only tobacco use and diet/activity patterns, and therefore, warrants the
      implementation of prevention strategies from a public health perspective. In sum,
      the public health model specifies three interrelated factors--the host, the agent
      or vehicle, and the environment--that focus strategies to reduce and/or prevent
      illness, injury and death. The paper concludes with specific examples of alcohol
      related public health strategies targeting the host (e.g., youth and families,
      minority groups), the agent/vehicle (e.g., alcohol content, labeling of
      containers, large containers), and the environment (e.g., motor vehicle operation
      BAC limits, zero tolerance laws, alcohol advertising).

PMID- 10927988
TI  - Integrated health sciences learning: a dream becomes reality.

PMID- 10927989
TI  - MetaStar sets Right Meds, Right Time workshops.

PMID- 10927990
TI  - Endocrine and metabolic disorders in anaesthesia and intensive care.

PMID- 10927991
TI  - Pituitary disease and anaesthesia.

PMID- 10927992
TI  - Thyroid disease.
AB  - In summary, disease of the thyroid gland is common. Anaesthetists will be
      required to manage patients with hypothyroidism and hyperthyroidism and those
      requiring thyroidectomy. Since anaesthesia for thyroidectomy provides many
      challenges of airway management, the anaesthetist should pay particular attention
      to preoperative assessment of the airway and should be able to deal with acute
      airway complications in the perioperative phase.

PMID- 10927993
TI  - Parathyroid disease and calcium metabolism.

PMID- 10927994
TI  - Phaeochromocytoma--recent progress in its management.

PMID- 10927995
TI  - Hormones and the gut.

PMID- 10927996
TI  - Insulin: understanding its action in health and disease.

PMID- 10927997
TI  - Anaesthetic management of patients with diabetes mellitus.

PMID- 10927998
TI  - Obesity in anaesthesia and intensive care.

PMID- 10927999
TI  - The stress response to trauma and surgery.

PMID- 10928000
TI  - Malignant hyperthermia: advances in clinical management and diagnosis.

PMID- 10928001
TI  - Neuroleptic malignant syndrome.

PMID- 10928002
TI  - Metabolic consequences of drug misuse.

PMID- 10928003
TI  - Porphyrias.

PMID- 10928004
TI  - Placement of double lumen tubes--time to shed light on an old problem.

PMID- 10928005
TI  - The Haldane effect--an explanation for increasing gastric mucosal PCO2 gradients?

PMID- 10928006
TI  - The Haldane effect--an explanation for increasing gastric mucosal PCO2 gradients?

PMID- 10928007
TI  - Surgery for fractured femur and elective ICU admission at 113 yr of age.

PMID- 10928008
TI  - Surgery for fractured femur and elective ICU admission at 113 yr of age.

PMID- 10928009
TI  - Increasing isoflurane concentration may cause paradoxical increases in the EEG
      bispectral index in surgical patients.

PMID- 10928010
TI  - Flexiblade and oral trauma.

PMID- 10928011
TI  - Ropivacaine 0.75% for epidural anaesthesia in a patient with severe Takayasu's
      disease.

PMID- 10928012
TI  - Midazolam premedication and thiopental induction of anaesthesia.

PMID- 10928013
TI  - Patient-controlled analgesia in labour.

PMID- 10928014
TI  - Difference in pre-intervention and post-intervention thromboelastography times.

PMID- 10928015
TI  - Separating the treatment effect of atropine from its prophylactic benefits during
      inhalational induction of anaesthesia in young children.

PMID- 10928016
TI  - Side-effects of alcoholic iodine solution (10%)

PMID- 10928017
TI  - Paediatric intensive care.

PMID- 10928018
TI  - The wrong message?

PMID- 10928019
TI  - Innovation in the pharmaceutical industry.

PMID- 10928020
TI  - Urgency of caesarean section: a new classification.
AB  - A new classification for caesarean section was developed in a two-part study
      conducted at six hospitals. Initially, 90 anaesthetists and obstetricians graded
      ten clinical scenarios according to five different classification methods--visual
      analogue scale; suitable anaesthetic technique; maximum time to delivery;
      clinical definitions; and a 1-5 rating scale. Clinical definitions was the most
      consistent and useful, and this method was then applied prospectively to 407
      caesarean sections at the same six hospitals. There was close agreement (86%)
      between anaesthetists and obstetricians for the five-point scale (weighted kappa
      0.89), increasing to 90% if two categories were combined (weighted kappa 0.91).
      We suggest that the resultant four-grade classification system--(i) immediate
      threat to life of woman or fetus; (ii) maternal or fetal compromise which is not
      immediately life-threatening; (iii) needing early delivery but no maternal or
      fetal compromise; (iv) at a time to suit the patient and maternity team--should
      be adopted by multidisciplinary groups with an interest in maternity data
      collection.

PMID- 10928021
TI  - Autism and intellectual disability: diagnostic and treatment issues.

PMID- 10928022
TI  - Health surveys via the Internet: quick and dirty or rapid and robust?

PMID- 10928023
TI  - Nutritional needs of refugee children in the UK.

PMID- 10928024
TI  - Unusual causes of small-bowel obstruction.

PMID- 10928025
TI  - Keeping up: continuing education or lifelong learning?

PMID- 10928026
TI  - Wriggling muscles as a sign of lung carcinoma.

PMID- 10928027
TI  - Unsuccessful treatment with cidofovir and cytarabine in progressive multifocal
      leukoencephalopathy associated with dermatomyositis.

PMID- 10928028
TI  - Symptomless hypercalcaemia: are you sure it's primary hyperparathyroidism?

PMID- 10928030
TI  - Cervical sympathetic chain dysfunction after whiplash injury.

PMID- 10928029
TI  - Autonomic neuropathy with B-cell lymphoma.

PMID- 10928031
TI  - Tracheostomy and tracheal intubation in military history.

PMID- 10928032
TI  - Mrs Starling's leg.

PMID- 10928033
TI  - Why doctors get so cross in Crown Courts.

PMID- 10928034
TI  - A coat of arms for paediatrics and child health.

PMID- 10928036
TI  - Was it a Galeazzi?

PMID- 10928035
TI  - Larva therapy.

PMID- 10928037
TI  - The cause and prevention of puerperal sepsis.

PMID- 10928038
TI  - Living wills.

PMID- 10928039
TI  - A voice for the National Health Service.

PMID- 10928040
TI  - Induction of Th1 response by dendritic cells pulsed with autologous melanoma
      apoptotic bodies.
AB  - BACKGROUND: We hypothesize that dendritic cells (DCs) can process antigens from
      autologous melanoma apoptotic bodies (MABs) and induce effector T cells in
      melanoma patients. MATERIALS AND METHODS: Peripheral blood mononuclear cells were
      obtained from three stage IV melanoma patients and adherent cells were cultured
      in complete medium (CM) containing GM-CSF (800 U/ml) and IL-4 (1000 U/ml) for 7
      days. Autologous MABs from melanoma cells following actinomycin D treatment (0.5
      microgram/ml) for 24 hours, were added to 72 hour DC culture. Autologous effector
      T cells were cultured in CM containing 60 IU/ml of IL-2 and were stimulated by
      MAB-pulsed DCs three times at a weekly interval. Effector T cells were harvested
      at the end of third cycle of DC stimulation. RESULTS: Using ELISPOT, IFN-gamma
      production by effector T cells stimulated by MAB-pulsed DCs was significantly
      higher than that by T cells without DC stimulation. Microscopy demonstrated
      phagocytosis of MABs by DCs. CONCLUSIONS: MAB-pulsed DCs are capable of
      stimulating Th1-directed autologous effector T cells. Pulsing DCs with autologous
      MABs may be a novel approach in future DC-based immunotherapeutic trials.

PMID- 10928041
TI  - Antitumor effect of IL-2, p53, and bax gene transfer in C6 glioma cells.
AB  - The use of interleukin-2 (IL-2) and p53 for immunotherapy and gene therapy for
      cancer has shown promising results. In this study, we examined the efficacy of
      plasmid gene therapy utilizing murine IL-2, the wild-type (wt) human p53 gene,
      the combination of these genes, and the murine bax gene, which are under the
      control of the cytomegalovirus (CMV) immediate-early promoter, in nude mice
      bearing established subcutaneous C6 glioma. In vitro assays and
      immunocytochemical analysis for therapeutic genes demonstrated expression of the
      proteins in C6 transfected cells. In animal studies, significant antitumor
      activity was observed for the IL-2, p53/IL-2, and bax treated groups. However, no
      synergistic effect was observed in the p53/IL-2 combination group. Demonstrating
      for the first time, bax showed a significant reduction of tumor volume when
      compared to p53 (p < 0.02). Thus, our in vivo studies show that delivery of naked
      therapeutic genes is safe and results in significantly slower progression of
      glioma in athymic rodents.

PMID- 10928042
TI  - Translational control of malignancy: the mRNA cap-binding protein, eIF-4E, as a
      central regulator of tumor formation, growth, invasion and metastasis.
AB  - Recent studies have implicated the mRNA cap-binding protein, eIF-4E, as a key
      regulator of malignant progression. Indeed, the major intracellular signaling
      pathways involved in tumor growth and malignancy, the MAP kinase and PI3 kinase
      pathways, induce eIF-4E activity. Furthermore, immunohistochemical analyses have
      revealed that eIF-4E is overexpressed and related to disease progression in human
      cancers of the colon, head and neck, and breast. In experimental tumors,
      manipulation of eIF-4E function profoundly affects not only tumorigenesis but
      also tumor invasion and metastasis. While increasing global protein synthesis
      rates, the increased activity of eIF-4E that typifies both human and experimental
      tumors disproportionately enhances the translation of a specific array of potent
      growth regulatory and malignancy-related proteins, including c-myc, cyclin D1,
      ornithine decarboxylase, vascular endothelial growth factor, basic fibroblast
      growth factor and others. Herein, we review the data supporting the notion that,
      by coordinately upregulating the translation of numerous malignancy-related
      proteins, eIF-4E plays a pivotal role in regulating not only tumor growth, but
      also invasion and metastasis.

PMID- 10928043
TI  - Chemosensitivity testing of irinotecan (CPT-11) in ovarian and endometrial
      carcinomas: a comparison with cisplatin.
AB  - BACKGROUND: The tetrazolium dye (MTT) assay is useful in predicting
      chemosensitivity. MATERIALS AND METHODS: Using an MTT assay, we designed an in
      vitro chemosensitivity test for irinotecan (CPT-11) and compared it with
      sensitivity to cisplatin in gynecologic carcinomas removed from 49 patients.
      RESULTS: The mean tumor inhibition rate (I.R.: %) for irinotecan was relatively
      inferior to the I.R. for cisplatin in both ovarian and endometrial carcinomas
      [40.2 vs 53.2 and 43.5 vs 58.0] (p < 0.05, respectively). In ovarian carcinomas,
      13 (48.1%) of 27 cases were irinotecan-sensitive (I.R. > or = 50%) and 77% of the
      tumors were judged to be irinotecan and/or cisplatin-sensitive. There was no
      significant difference in the I.R. for irinotecan among the various histologic
      subtypes. Comparing in vitro sensitivity to irinotecan with clinical responses in
      8 patients who received irinotecan, the overall accuracy of the MTT assay for
      evaluating clinical effectiveness was 75% (6 out of 8). In endometrial
      carcinomas, we found 9 (40.9%) out of 22 cases to be irinotecan-sensitive. The
      I.R. for irinotecan in G1 carcinomas [33.5] was significantly lower than in G2
      carcinomas [59.3] (p < 0.05). CONCLUSION: Our data suggest that irinotecan
      appears to have moderate antitumor activity in vitro against both ovarian and
      endometrial carcinomas and that differences in irinotecan sensitivity among the
      histologic subtypes were evident in the latter but not in the former.

PMID- 10928044
TI  - Adenovirus-mediated combination suicide and cytokine gene therapy for bladder
      cancer.
AB  - BACKGROUND: The present study tests the hypothesis that adenovirus-mediated
      transfer of murine IL-2 (ADV/RSV-mIL-2) alone or in combination with HSV-tk + GCV
      will improve antitumorigenic response in the murine MBT-2 model. MATERIALS AND
      METHODS: mIL-2 production and toxicity were determined in vitro using an ELISA
      and a cell proliferation assay. Tumor-bearing animals were randomly assigned into
      four treatment groups and directly injected with combinations of ADV/RSV-tk and
      ADV/RSV-mIL-2. In a separate experiment, the above-mentioned groups were followed
      by two subsequent treatments with ADV/RSV-mIL-2. RESULTS: Transduced MBT-2 cells
      were able to express mIL-2 in a time and dose dependent fashion. We could not
      demonstrate any improvement in antitumorigenic response with mIL-2 gene therapy
      alone or in combination with HSV-tk-suicide gene therapy over HSV-tk suicide gene
      therapy alone. CONCLUSIONS: Although ADV/RSV-mIL-2 transduced MBT-2 cells were
      able to produce large amounts of mIL-2 in vitro, we could not demonstrate
      significant tumor growth inhibition by adding mIL-2 gene therapy to suicide gene
      therapy. The growth inhibitory effects of sequential suicide and cytokine gene
      therapy were transient and not superior to single dose suicide and cytokine gene
      therapy.

PMID- 10928045
TI  - Novel synthetic organosulfur compounds induce apoptosis of human leukemic cells.
AB  - It has been well documented that natural organosulfur compounds (OSCs) derived
      from plants such as garlic, onions and mahogany trees possess antiproliferative
      properties; however, the essential chemical features of the active OSC compounds
      remain unclear. To investigate the association between OSC structure and growth
      inhibitory activity, we synthesized novel relatives of dysoxysulfone, a natural
      OSC derived from the Fijian medicinal plant, Dysoxylum richii. In this study, we
      have examined the antiproliferative effects of these novel OSCs on a model human
      leukemic cell system and show that the compounds segregate into three groups.
      Group I, consisting of compounds A, B, G and J, did not affect either cell
      proliferation or the cell cycle profile of the leukemic cell lines. Group II,
      consisting of compounds F and H, induced the cells to undergo apoptosis from the
      G2/M phase of the cell cycle. Group III, consisting of compounds C, D, E and I,
      decreased cell proliferation and induced apoptosis throughout the cell cycle. The
      apoptotic agonists of Group II and III shared a common disulfide moiety,
      essential for leukemic cell cytotoxicity. Interestingly, Group II compounds did
      not affect cell viability of normal human diploid cells, suggesting the regions
      flanking the disulfide group contributes to the specificity of cell killing.
      Thus, we provide evidence that structure-activity analysis of natural products
      can identify novel compounds for the development of new therapeutics that can
      trigger apoptosis in a tumor-specific manner.

PMID- 10928046
TI  - In vitro PET evaluations in lung cancer cell lines.
AB  - One purpose of the study was to explore the PET tracer 11C-L-DOPA for the
      discrimination between small-cell lung cancer (SCLC) and non small-cell lung
      cancer (NSCLC). A further aim was to explore the potential antitumoral effects of
      6-diazo-5-oxy-L-norleucine (DON) and the use of a PET proliferation marker for
      the evaluation. MATERIALS AND METHODS: Four lung cancer and one endocrine tumour
      cell line (BON) were cultured as monolayer. The uptake of 5-[76Br]-bromo-2-fluoro
      deoxyuridine (76Br-BFU), [11C]-L-DOPA (11C-DOPA) and [18F]-fluorodeoxyglucose
      (18FDG) were evaluated. The effects of specific enzyme inhibitors affecting the
      DOPA metabolism were explored. The effect of DON on proliferation and uptake of
      76Br-BFU were assessed. RESULTS: All cell types showed a measurable uptake of 11C
      DORA, with slightly lower values in lung cancer. There were no clear differences
      between SCLC and NSCLC. The addition of COMT inhibitor induced a significantly
      increased uptake of the tracer in BON cells, but not in lung cancer cells. DON
      significantly reduced the proliferation in all cell lines. The 76Br-BFU uptake
      was reduced markedly in all cell lines during DOn treatment. CONCLUSION: 11C-DOPA
      failed to distinguish between SCLC and NSCLC. DON showed strong antiproliferative
      effects which might motivate renewed interest in this drug for clinical cancer
      treatment. PET with 76Br-BFU might be used for treatment evaluation.

PMID- 10928048
TI  - Expression of E-cadherin is associated with squamous differentiation in squamous
      cell carcinomas.
AB  - E-cadherin is a cell surface molecule that mediates cell-cell adhesion in normal
      epithelium. Disabled or aberrant E-cadherin expression increases cell motility
      and promotes the transition of well-differentiated adenoma to invasive carcinoma.
      To evaluate whether E-cadherin could serve as a biomarker of squamous cell
      differentiation, we analyzed its expression by immunohistochemistry in formalin
      fixed, paraffin-embedded tissue sections of 7 head and neck cancer patients, 19
      lung cancer patients, 73 esophageal cancer patients, 19 skin cancer patients, and
      18 cervical cancer patients. E-cadherin was expressed at very high levels (93%
      100%) in adjacent or distant normal squamous epithelia. Likewise, most (75-100%)
      well-differentiated squamous cell carcinomas (SCCs) also expressed E-cadherin. In
      contrast, poorly differentiated SCCs expressed less than 40% of E-cadherin.
      Furthermore, immunohistochemical analysis showed that the differentiation
      inducing agent, all-trans retinoic acid, can up-regulate E-cadherin expression in
      esophageal SCC cells in vitro. Our data demonstrated that E-cadherin expression
      is associated with SCC differentiation and that may serve as a squamous cell
      differentiation marker.

PMID- 10928047
TI  - Bioadhesive peptides as potential anticancer drug carriers: activation via
      isopeptide deblocking by proteases.
AB  - BACKGROUND: Bioadhesive peptides are potentially useful as anticancer drug
      carriers, if the bioadhesivity becomes active only at the tumor site. We propose
      that this function can be achieved by the prodrug strategy using proteases in
      tumors. MATERIALS AND METHODS: A laminin fragment peptide, Ac-AASIKVAVSADR-NH2
      (5), and its derivatives, Ac-AASIK(L) VAVSADR-NH2 (6), Ac-AASIDpm(NH2)VAVSADR-NH2
      (7) and Ac-AASIDpm(L)(NH2)VAVSADR-NH2 (8), were synthesized and tested for their
      bioadhesive activity with 6 cancer cell lines. RESULTS: The strength of the
      binding was in the order of 5 >> 7 > or = 8 > or = 6. The attachment of mouse
      whole blood cells to peptide 6-coated surface was also weaker than to 5-coated
      surface. The Leu isopeptide linkage in 6 was enzymatically cleaved by the cells.
      CONCLUSION: The present results suggest that isopeptide 6, working as a prodrug
      form for the bioadhesive peptide 5, could serve as an anticancer drug carrier for
      tumor targeting.

PMID- 10928049
TI  - Effect of selenium in combination with Adriamycin or Taxol on several different
      cancer cells.
AB  - The anti-neoplastic properties of an Selenium compound were studied in vitro on
      several tumor cell lines: Breast (MCF-7, MCF-10, SKBR-3, BCAP37), Lung (RH2),
      Prostate (LNCap and PC-3), Colon (T84, Caco-2), Small Intestine (HCF8), and Liver
      (HepG2). We also examined additive or synergistic effect of Selenium in
      combination with standard anti-cancer drugs, Adriamycin (Doxorubicin) and Taxol.
      The effect of Selenium was assessed by apoptosis; DNA synthesis; growth rate by
      MTT assay; uptake of amino acid MeAIB by System A; and morphological changes. Our
      results demonstrate that MCF-7 and SKBR-3 showed increase in apoptosis as
      measured by DNA fragmentation and increase in "rounded" cells and membrane
      "blebbing", decrease in MeAIB uptake, and decrease in DNA synthesis. These
      changes were Selenium dose dependent with optimal inhibition at Selenium
      concentration between 4 and 40 ng/ml after 72 hrs of treatment. Similar
      observations were made with RH2, HCF8, Caco-2, and HepG2 cells. In contrast,
      LNCap, PC-3, and T-84 were not significantly affected by Selenium. However,
      addition of Adriamycin or Taxol in combination with Selenium caused small but
      significant inhibition of prostate cancer cells LNCap and PC-3. Addition of
      chemotherapeutic agents either Taxol or Doxorubicin with Selenium caused further
      inhibition of MCF-7, SKBR-3, RH2, HCF8, and HepG2 cells. In conclusion, Selenium
      has a significant anti-neoplastic effect on breast, lung, liver, and small
      intestinal tumor cells. Supplementation of Selenium enhanced chemotherapeutic
      effect of Taxol and Doxorubicin in these cells beyond that seen with the
      chemotherapeutic drugs used alone. These in vitro studies on several cancer cell
      lines suggest a potential benefit of Selenium-enhancement of anticancer effects
      other systems, and therefore offer further relevance to clinical trials efforts.

PMID- 10928050
TI  - Sequence-dependent antagonism between tamoxifen and methotrexate in human breast
      cancer cells.
AB  - High-dose methotrexate (MTX) cytotoxicity is decreased in MCF-7 breast cancer
      cells when the chemoendocrine agent tamoxifen (TAM) is given to cells 24 hours
      prior to MTX (early TAM). However, when breast cancer cells are exposed to TAM 24
      hours after MTX (delayed TAM), MTX cytotoxicity is enhanced by TAM. The growth of
      cells exposed to 10 microM TAM and 10 microM MTX alone or in combination with
      early TAM plus MTX had the following order: TAM > TAM (early) + MTX > MTX. The
      percentages of control rates for TAM, MTX, and TAM (early) + MTX are 74.71 +/-
      1.36%, 22.13 +/- 2.76%, and 38.17 +/- 2.75%, respectively. The inhibitory
      sequence from cells exposed to MTX + TAM (delayed TAM), MTX and TAM alone is MTX
      + TAM (delayed TAM) > MTX > TAM; and the percentages of control rates were 16.87
      87% (MTX + TAM [delayed TAM]), 25.92 +/- 2.14% (MTX), and 54.08 +/- 14.79% (TAM).
      These studies suggest that: (a) the interactions between TAM and MTX are sequence
      dependent; (b) TAM antagonizes the effect of MTX when TAM administration precedes
      MTX; and (c) TAM enhances the effect of MTX when TAM administration follows MTX.

PMID- 10928051
TI  - Expression of focal adhesion kinase (p125 FAK) and proline-rich tyrosine kinase 2
      (PYK2/CAKb) in cerebral metastases, correlation with VEGF-R-, ecNOS III-labelling
      and morphometric data.
AB  - BACKGROUND: Cerebral metastasis occurs in about 20% of all neurosurgical
      patients. Cerebral metastases have a typical spherical morphology with a common
      central necrosis and perifocal oedema. It has been proposed that oedema
      extension, tumour volumes and infiltrative behaviour are partially mediated by
      vascular endothelial growth factor (VEGF) and nitric oxide (NO). In several
      systemic tumour entities NO is suggested as a factor which influences the
      metastatic potential. VEGF has recently been reported to influence the matrix
      related migratory activity by interaction with focal adhesion kinase (p125FAK)
      and proline-rich tyrosine kinase beta (PYK2/CAK beta). Nitric oxide, which is
      produced in metastases by three different NOS isozymes is capable of antagonizing
      the binding of FAK to matrix integrins. NO, VEGF and FAK/PYK 2 are therefore
      considered to be important mediators of the cerebral metastatic incidence,
      growth, infiltration and oedema extension. The aim of our present study was to
      investigate the expression of p125FAK and the coexpression with PYK2/CAK beta,
      VEGF-receptor FLT-1, NOS isozymes NOS I-III, capillary density and the histology
      in 130 specimens of resected cerebral metastatic tumours. A further analysis was
      performed to morphometrically evaluate tumour and oedema volumes and to correlate
      the immunohistochemical data in a subgroup of 40 patients. MATERIALS AND METHODS:
      Cryosections (N = 130) of metastatic resections were investigated
      immunohistologically using a 4-step scoring evaluation for the expression of NOS
      I-III, VEGF-receptor FLT-1, and capillary vessel presence by endothelial Von
      Willebrand-Factor (VWF) staining. Tumour and oedema extension was measured in
      preoperative MRI (N = 40) scans by an image-processing device (Kontron) and the
      ratios of oedema volumes to total tumour volumes were calculated. The data were
      analysed statistically (Spearman rank order correlation and Kruskal-Wallis ANOVA)
      and correlated with the clinical data. RESULTS: FAK immunoexpression was observed
      in 50% of the specimens (31.2% gradings 2 and 3). We observed a significant
      coexpression (p = 0.0001) with PYK 2 labelling which occurred frequently in 74%
      of the specimens (42% gradings 2 and 3). The VEGF receptor FLT-1 could be
      detected in 70% of them, 24% at higher expression values 2 and 3. The expression
      of NO synthase was frequently observed. NOS I was detected in 83.6% of the
      specimens, values 2 and 3 in 40.5%. NOS III, the endothelial isoform, was
      observed in 39.4% of the specimens (gradings 2 and 3) and inducible NOS II in
      29.4% (grading 2 and 3) of them. Coexpressions were statistically significant for
      FAK and NOS III (Spearman p = 0.008) and FAK and VEGF-R (p = 0.03). The
      morphometric evaluation resulted in tumour volumes between 2.0 and 83 cm3 (mean
      22.5 +/- 19.1 SD) with oedema ratios between 0 and 100% (mean 62.2 +/- 22.5 SD).
      FAK expression correlated significantly (p = 0.06) with tumour volumes and
      histology. CONCLUSION: The frequent histotypic occurrence of FAK and PYK2 in
      metastases could be an important factor in the modulation of metastatic capacity
      and infiltrative behaviour and might influence the disease course. Judging from
      its frequent expression PYK2 may generate the more relevant signals. A further
      aspect is the possible interaction with endothelial NOS III and VEGF receptor,
      which could be important for the infiltrative behaviour in a latent hypoxic
      scenery and environment.

PMID- 10928052
TI  - Role of metastatic potential in the adhesion of human breast cancer cells to
      endothelial monolayers.
AB  - To gain further insight into the process of metastasis, adhesion to endothelial
      monolayers was compared for a nonmetastatic and a highly metastatic human breast
      cancer cell line. The parallel plate flow chamber was employed to quantify
      adhesion using an attachment assay. This assay was carried out at several
      physiological shear stresses both with and without endothelial TNF-alpha
      stimulation. At a venular shear stress of 1 dyne cm-2, the nonmetastatic cell
      line was more adhesive to stimulated endothelial monolayers, while no differences
      could be noted for resting monolayers. At a lower shear stress of 0.25 dynes cm
      2, the highly metastatic cell line was more adhesive to stimulated endothelial
      monolayers, while the nonmetastatic cell line was more adhesive to resting
      monolayers. Thus, metastatic potential correlated with attachment only at low
      shear stresses and following endothelial stimulation. These results emphasize the
      importance of studying cancer cell adhesion under multiple physiological flow
      conditions. Furthermore, these results indicate that adhesion of these two cell
      lines may be controlled by two different mechanisms. Antibody blocking
      experiments of adhesion molecules on the endothelial cells confirmed that
      adhesion of the nonmetastatic cell line was mediated by E-selectin expressed on
      the endothelial cells and adhesion of the highly metastatic cell line was
      mediated by both E-selectin and VCAM-1 expressed on the endothelial cells.

PMID- 10928053
TI  - Hypomethylation of cytosine 5-methyltransferase in human neoplasms.
AB  - Cytosine methylation is an epigenetic modification of DNA involved in control of
      gene expression. Neoplastic cells exhibit various alterations both in DNA
      methylation and activity of the enzyme responsible for this modification, 5
      methyltransferase (5-MeTase). As there is little requirement for 5
      methyltransferase expression in normal cells except during mitosis, we argued
      that the gene would be hypermethylated in normal cells. Southern analysis
      revealed almost complete methylation of the gene in genomic DNA from the
      peripheral blood leukocytes of healthy subjects and a primary fibroblast derived
      cell line. In contrast, in DNA from a range of tumour tissues and tumour derived
      cell lines, 5-MeTase exhibited marked hypomethylation. The results of this study
      indicate that dysregulation of the DNA methylating machinery, especially with
      respect to the methylation status of 5-MeTase, is a feature of a wide range of
      neoplasms.

PMID- 10928054
TI  - Antitumor effects of soybean hypocotyls and soybeans on the mammary tumor
      induction by N-methyl-n-nitrosourea in F344 rats.
AB  - BACKGROUND: Soybeans are reported to have cancer inhibitory effects, probably due
      to their isoflavones. Soybean hypocotyls are embryo buds of soybeans and contain
      a higher amount of isoflavones and other factors than soybeans themselves.
      MATERIALS AND METHODS: The effects of soybean protein and soybean hypocotyls as
      diets on the development of N-methyl-n-nitrosourea (MNU) induced tumors were
      examined in female F344 rats. For this trial, 120 animals were used and at 6
      weeks of age, groups of 30 animals were fed diets containing casein, soy protein
      isolate (SPI), 1.5% soybean hypocotyls and 5% soybean hypocotyls. Three weeks
      later all the animals except the control animals received a first dose (37.5
      mg/kg body weight) of MNU by tail vein injection. At 29 weeks of age the animals
      received a second MNU dose (50 mg/kg body weight). Testing was performed 42 weeks
      after the first MNU dose. RESULTS: Analysis of cumulative palpable tumor
      incidence indicated that final tumor development of the SPI diet group and the
      hypocotyl diet groups was less than that of the casein diet group. Tumors were
      detected in one or more sites from 9 out of 24 rats in the casein diet group, 5
      of 20 rats in SPI diet group, 6 out of 24 rats in the 1.5% hypocotyl diet group
      and 6 out of 23 rats in the 5% hypocotyl diet group. Pairwise comparisons
      indicated that the formation of tumors during the experiment was significantly
      less rapid in the SPI diet group and the hypocotyl diet groups than the casein
      group. No difference in tumor promotion was observed between the SPI diet group
      and the soybean hypocotyl diet groups. CONCLUSION: Our results suggest that
      dietary soybeans and soybean hypocotyls are capable of suppressing tumor
      promotion.

PMID- 10928055
TI  - Relationship between apoptosis and immunohistochemical staining for proliferating
      cell nuclear antigen and Ki-67 in non-small cell lung cancer.
AB  - The relationship between apoptosis and cellular proliferative activity in human
      non-small cell lung cancer (25 cases) was investigated using the in situ DNA nick
      end labeling method and immunohistochemistry for both proliferating cell nuclear
      antigen (PCNA) and Ki-67 antigen. Comparison of the distribution of Ki-67
      positive cells to that of apoptotic cells shows an inverse correlation in semi
      serial sections. The PCNA labeling rates were closely correlated with Ki-67
      labeling rates in non-small cell lung cancer. It was concluded that the
      immunostainings of PCNA and Ki-67 were almost equally valuable for assessing the
      proliferative activity in paraffin-embedded tissue from non-small cell lung
      cancer and that apoptosis may be related with the cell cycle in this cancer.

PMID- 10928056
TI  - LEA.135 expression: its comparison with other prognostic biomarkers for patients
      with primary breast carcinoma.
AB  - The purpose of this retrospective study was to examine the prognostic value of
      expression of luminal epithelial antigen (LEA.135) for recurrence and overall
      survival of patients with primary invasive breast carcinoma by both univariate
      and multivariate analyses. The possible prognostic value of LEA.135 was also
      compared with some widely utilized prognostic biomarkers such as c-erbB 2,
      topoisomerase II.alpha (TPII.alpha), MIB 1, estrogen receptor (ER) and
      progesterone receptor (PR), as well as age of the patients and clinicopathologic
      parameters. The study was carried out by immunohistochemical methods on formalin
      fixed/paraffin-embedded tissue sections in a series of 225 patients with median
      follow-up of 8.5 years. Prognostic significance of the biomarkers was determined
      by two-sided p value. In this series of patients, among the age and
      clinicopathologic parameters, only age, was significantly associated with a
      decreased overall survival (logrank p = 0.027). Among the prognostic biomarkers,
      TPII a expression at high (> 50% positive cells) or moderate (6-50% positive
      cells) level was associated with an increased rate of recurrence (logrank p <
      0.001). However, the association of TPII.alpha expression with a decreased
      overall survival failed to reach a statistically significance. Expression of c
      erbB 2 showed a trend of being associated with an increased probability of
      recurrence, but the association did not reach statistical significance. The
      remaining biomarkers were not associated with either the probability of
      recurrence or overall survival. LEA.135 expression was observed in 163 (72.4%) of
      the 225 patients. The patients with high (> 50% positive cells) or moderate (6
      50% positive cells) level of LEA.135-positive cancer cells showed a significantly
      decreased probability of recurrence (logrank p < 0.001) and an increased overall
      survival (logrank p < 0.001) compared with those with LEA.135-negative cancer
      cells. The association remained significant by multivariate analysis for
      recurrence (likelihood ratio test p < 0.001) and overall survival (likelihood
      ratio test p < 0.001) when assessed with other prognostic parameters.
      Furthermore, the combination of LEA.135 with other prognostic biomarkers
      stratified four subgroups of patients with distinct clinical outcome. The
      subgroup of patients who were LEA.135+/TPII.alpha- showed the lowest probability
      of recurrence and the longest overall survival compared with those who were
      LEA.135-/TPII.alpha+ (logrank p < 0.001). Interestingly, the patients whose
      cancer cells were LEA.135+/TPII.alpha+, LEA.135+ MIB.1+ or LEA.135+/c-erbB 2+
      experienced a decreased probability of recurrence and an increased overall
      survival compared with those with LEA.135-/TPII.alpha+, LEA.135- MIB.1+ or
      LEA.135-/c-erbB 2+ (logrank p < 0.001). The results demonstrated that LEA.135 is
      an independent and favorable prognostic biomarker for patients with primary
      invasive breast carcinoma, that the loss of LEA.135 expression is associated with
      aggressive phenotype of cancer cells during the breast cancer progression, and
      that its continued expression seems to override the adverse effects of expression
      of an oncogene or cell proliferation-associated molecules.

PMID- 10928057
TI  - Changes in mRNAs for enzymes of glutamine metabolism in the tumor-bearing mouse.
AB  - Changes in the relative mRNA levels of phosphate-activated glutaminase (PAG) and
      glutamine synthetase (GS) in the liver and kidney of mice bearing a highly
      malignant strain of Ehrlich ascites tumor cells were determined at different days
      after tumor transplantation. Kidney glutaminase mRNA steadily increased, reaching
      maximum values at day 10 of tumor growth, while those of glutamine synthetase did
      not change, resulting in a sustained decrease of the GS/PAG ratio in the kidneys
      of tumor-bearing animals compared with controls. However, the GS/PAG ratio in the
      liver significantly increased, mainly due to a strong decrease in PAG, whereas GS
      mRNA levels remained almost unaffected. These results, combined with those
      previously reported on enzymatic activities and glutamine concentrations in the
      host-tumor system, suggest a long-term regulation of the host glutaminase enzymes
      in order to increase the circulating glutamine levels needed for tumor growth.

PMID- 10928058
TI  - Technetium-99m tetrofosmin mammoscintigraphy findings related to the expression
      of P-glycoprotein mediated multidrug resistance.
AB  - We studied 30 patients with infiltrating ductal breast carcinomas to evaluate the
      relationship between the degree of accumulation of technetium-99m tetrofosmin (Tc
      TETRO) and p-glycoprotein (Pgp) expression in breast tumor tissues. All of the 30
      patients underwent Tc-TETRO mammoscintigraphy to calculate breast tumor uptake of
      Tc-TETRO to background (T/B) ratios before surgery or biopsy. Immunohistochemical
      analysis was performed to determine Pgp expression in the pathological specimens
      of the 30 breast tumors. The T/B ratios were significantly lower for tumors in 12
      patients with positive Pgp expression (Group A) than for those in 18 patients
      with negative expression (Group B) (1.20 +/- 0.12 and 1.94 +/- 0.30, p < 0.05).
      Our results supported the opinion that Tc-TETRO mammoscintigraphy is helpful for
      determining in vivo the presence of multidrug resistance due to Pgp expression in
      breast carcinoma patients.

PMID- 10928059
TI  - Inhibition of histone deacetylases: a new strategy to target epigenetic
      modifications for anticancer treatment.
AB  - The role of epigenetic modifications due to deregulated acetylation of
      nucleosomes with respect to its role in progression and etiology of human cancer
      is discussed. Among the mediators of these phenomena are the histone
      deacetylases, a class of enzymes consisting of at least two subfamilies with a
      total of at least 7 members in mammals. Depending on the cell-type, inhibition of
      HDACs in cancer cells can lead to transcriptional activation and silencing of
      about 2% of human genes, cell-cycle arrest and induction of apoptosis and
      differentiation in vitro and in vivo. This paper discusses several inhibitors of
      HDACs primarily derived from natural sources, their physiological consequences in
      different in vitro and in vivo cancer-related systems, their stage of preclinical
      and clinical development as well as their potential as antineoplastic agents. It
      is of paramount importance to elucidate the molecular mechanisms resulting in
      cell-cycle arrest, apoptosis or differentiation after inhibition of HDACs and to
      investigate the physiological function of the different HDAC isoenzymes and their
      deregulation in human cancers in order to devise optimized therapeutic
      intervention in cancer patients.

PMID- 10928060
TI  - Genetic alternations of p73 are infrequent but may occur in early stage
      hepatocellular carcinoma.
AB  - p73, a structural homologue of the tumor suppressor gene, p53, has recently been
      identified and mapped to chromosome 1p36, where genomic loss of heterozygosity
      (LOH) often occurs in human hepatocellular carcinoma (HCC). To determine whether
      p73 is involved in the development of HCC and whether there is an inverse
      correlation between the mutations of p73 and p53, we examined 22 paired
      tumors/noncancerous liver tissues for allelic expression, LOH and mutation of p73
      and for mutation of p53. p73 was biallelically expressed in noncancerous liver
      tissues and in 7 out of the 8 informative tumors. One tumor tissue expressed only
      a single allele. LOH of p73 was found in 2 out of the 11 (18%) informative cases.
      A tumor-specific five-nucleotide deletion mutation causing a reading
      frameshift/early truncation of p73 DNA-binding domain was found, in which case no
      concomitant mutation in the DNA-binding domain of p53 was identified. Nine out of
      the 22 cases (41%) contained tumor-specific mutations in the DNA-binding domain
      of p53. Two of the three cases with p73 genetic alternations had a tumor size of
      less than 2 centimeters. These results suggest that p73 is a biallelically
      expressed gene in the liver and that allelic loss and mutation of p73 is
      infrequent and may occur early in HCC. p73 is unlikely to be the putative tumor
      suppressor gene located at chromosome 1p36 in HCC.

PMID- 10928061
TI  - Anti-promotion effect of chlorophyllin in DMBA-TPA-induced mouse skin
      carcinogenesis.
AB  - This study aimed to elucidate the inhibitory effects of chlorophyllin (CHL) at
      different promotion stages in a DMBA-TPA-induced mouse skin carcinogenesis model.
      TPA promotion was undertaken for 6, 18 and 24 weeks, respectively. Proliferating
      activity was observed immunohistochemically and the ornithine decarboxylase (ODC)
      mRNA level was analyzed by reverse transcriptase-polymerase chain reaction.
      Messenger RNAs for c-fos, c-jun and jun-B were also observed. CHL treatment
      clearly reduced proliferating activity and the level of ODC mRNA at the 18-week
      promotion stage. When promoted for 24 weeks, CHL was not effective in reducing
      proliferating activity and ODC mRNA expression. These results indicate that the
      promotion stage of each target tissue should be considered in a chemopreventive
      program.

PMID- 10928062
TI  - Microsatellite instability(MSI) in non-small cell lung cancer(NSCLC) is highly
      associated with transforming growth factor-beta type II receptor(TGF-beta RII)
      frameshift mutation.
AB  - BACKGROUND: TGF-beta type II receptor (TGF-beta RII) mutations associated with
      microsatellite instability(MSI) are characteristically frameshift mutations
      within a 10 bp poly-A tract. These frameshift mutations have been reported to be
      common in colorectal and gastric cancers with MSI, though, rarely reported in non
      small cell lung cancer (NSCLC). MATERIALS AND METHOD: In this study, we analysed
      MSI and TGF-beta RII frameshift mutations in 7 NSCLC cell lines and 21 surgically
      resected NSCLC tissues. Determination of MSI in NSCLC was performed using primer
      sets for BAT-25, BAT-26 and BAT-40. In order to examine the presence of the
      frameshift mutations of TGF-beta RII in samples with MSI, sequencing for TGF-beta
      RII poly-A tract was performed. RESULTS: MSI was observed in 5 out of 7 NSCLC
      cell lines and 3 out of 21 NSCLC tissues. Six out of 8 samples with MSI(75%)
      showed frameshift mutations in TGF-beta RII poly-A tract. CONCLUSION: These
      results suggest that MSI is highly associated with TGF-beta RII frameshift
      mutations in NSCLC and further support the hypothesis that TGF-beta RII plays an
      important role in NSCLC carcinogenesis.

PMID- 10928063
TI  - The effect of irradiation on mitotic and apoptotic frequency in head and neck
      cancer cell lines, the correlation to p53 mutations and clonogenic survival.
AB  - It was our intention to enlighten the controversy between the mainstream of
      studies and our previous results showing a correlation between the intrinsic
      radiosensitivity and the p53 allele status of 20 human head and neck squamous
      cell carcinoma (HNSCC) cell lines. In our study cell lines carrying a wild-type
      (WT) p53 allele were significantly more radioresistant than cell lines which
      lacked a WT gene. We observed nine HNSCC cell lines with known intrinsic
      radiosensitivity and p53 allele status with time-lapse video microscopy after
      irradiation with 2 and 3 Gy. We studied the mitotic and apoptotic frequencies and
      scored the apoptoses as to whether they occurred morphologically in mitosis or in
      interphase. Irradiation with 2 or 3 Gy did not induce apoptosis in the cell lines
      studied. As expected the mitotic frequency was reduced by the irradiation. This
      was statistically significant in the cell lines which were radiosensitive when
      measured with a clonogenic assay. p53 allele status did not have an independent
      effect on the cell lines, except that the irradiation favoured the apoptosis in
      mitosis in the cell lines with WT p53 and the apoptosis in the interphase in the
      cell lines with a mutated or non-functional p53 gene. We conclude that although
      the apoptosis is not induced by irradiation with 2 Gy or 3 Gy, the p53 suppressor
      gene seems to influence the process of apoptosis after irradiation in the cell
      lines studied.

PMID- 10928064
TI  - Antimetastatic action of a new analog of dacarbazine in mice bearing Lewis lung
      carcinoma.
AB  - We report the selective antimetastatic properties of 3-(3,3-dimethyl-1-triazenyl)
      5-methyl-4,5-dihydroisoxazole in the murine transplantable tumor model Lewis lung
      carcinoma. The compound verifies a previous study on the correlation of
      antimetastatic, antitumor and cytotoxic properties of aryl- and
      heteroaryltriazenes with their Electron Ionization Mass Spectrometry (EI-MS)
      behavior. The new analog of dacarbazine exhibits a selective antimetastatic
      activity accompanied by limited thymus toxicity. The mechanism of action is
      unclear nevertheless any antiproliferative or cytotoxic effect is excluded.

PMID- 10928065
TI  - Haematological toxicity following different dosing schedules of 5-fluorouracil
      and epirubicin in rats.
AB  - AIM: To study the effects of single and fractionated doses of 5-fluorouracil and
      epirubicin on the leukocyte counts in rats. METHODS: Six different dosing
      patterns of each drug were injected within one day. The leukocytes were followed
      for 11-15 days. Pharmacokinetic models were developed using NONMEM. Quantitative
      and qualitative pharmacokinetic-pharmacodynamic relationships were investigated.
      RESULTS: A one-compartment model with non-linear elimination described 5
      fluorouracil pharmacokinetics and a three-compartment model described epirubicin
      concentration data. Sigmoidal or basic Emax-models quantified the relationships
      between individual AUCs and decreases in leukocytes, for both drugs. Similar
      relationships between AUC and toxicity were found, regardless of whether the
      drugs were given as single or fractionated doses. CONCLUSION: Quantitative
      relationships between AUC and the effect on leukocytes were established for 5
      fluorouracil and epirubicin. However, no schedule dependence was indicated for
      the schedules used in the study.

PMID- 10928066
TI  - Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and
      proliferation in lung cancer.
AB  - Hypoxia-inducible factor 1 (HIF-1) plays an important role in the pleiotropic
      response observed under hypoxia. In this study we examined whether a relationship
      exists between HIF-1 proteins and proliferation and apoptosis in lung cancer. To
      this purpose, we used immunohistochemistry to analyze HIF-1 alpha and HIF-1 beta
      in formalin-fixed, paraffin-embedded, non-small cell lung carcinomas (n = 96) and
      compared the HIF expression with cyclin A protein expression, cell cycle phases,
      the apoptotic index and the expression of caspase 3, Fas and Fas ligand.
      Additionally, we examined whether HIF-1 determinations can improve the prognostic
      information concerning a patient's overall survival. A relationship between HIF-1
      alpha or HIF-1 beta and proliferation could not be observed. However, a
      significant correlation between HIF-1 expression, apoptosis and the pro-apoptotic
      factors caspase-3, Fas, and Fas ligand could be detected. Patients with HIF
      positive carcinomas had significantly longer median survival times than patients
      with HIF-negative carcinomas (HIF-1 alpha: 191 vs. 60 weeks; P = 0.05; HIF-1
      beta: 111 vs. 41 weeks; P = 0.003). Multivariate analyses demonstrated that the
      presence of HIF-1 at a given stage or extent of lymph node involvement is an
      independent prognostic factor for the survival of patients with non-small cell
      lung carcinomas.

PMID- 10928067
TI  - Retinoid receptors: pathways of proliferation inhibition and apoptosis induction
      in breast cancer cell lines.
AB  - In this study we investigated the effects of several selective agonist retinoids
      (specific for RAR alpha, RAR beta, RAR gamma, and RXR alpha, respectively) on the
      proliferation and apoptosis of human breast cancer cell lines. All these
      retinoids inhibit proliferation through apoptosis induction, but with some
      differences among the tested molecules and the three cell lines. In particular,
      estrogen receptor positive (ER+) cells display a higher sensitivity to RARs
      selective compounds, the RAR alpha selective compound being the most effective
      agent, while estrogen receptor negative (ER-) cells show a greater responsiveness
      to the RXR alpha selective retinoid. In all tested cell lines a potent
      antiproliferative and apoptotic effect was also displayed by a high dose of the
      RAR gamma selective compound. The apoptosis induction is associated with bcl-2
      down-regulation, while p53 expression is not modified by any retinoid. Only in
      one cell line (ZR-75.1), after RAR alpha selective retinoid treatment is there an
      induction of RAR beta: therefore not only RAR beta induction but also other
      mechanisms may contribute to the growth inhibitory effect of retinoids in tested
      breast cancer cell lines.

PMID- 10928068
TI  - Gamma-ray induced hepatocarcinogenesis in p53-deficient mice.
AB  - BACKGROUND: Mutations in the p53 gene are frequent genetic alterations in human
      hepatocellular carcinoma (HCC), but, little is known of the molecular genetic
      changes that occur during murine hepatocarcinogenesis. MATERIALS AND METHODS: To
      characterize the properties of constitutive p53 deficiency that contribute to
      liver tumor development, a total of 168 F1 mice of two different strains (C3H,
      which are susceptible to hepatocarcinogenesis and MSM [Mus. M. molossinus] with a
      single null p53 allele) were exposed to a single 3-Gy dose of whole-body gamma
      irradiation at 4 weeks of age and observed for a period of 360 days. The genotype
      of the mice and the p53 spectrum of the tumors were investigated by polymerase
      chain reaction (PCR) analysis. RESULTS: Thirty-five gamma-ray-induced HCCs were
      obtained as a result of this experiment. 11 (40%) of the mice with liver tumor
      were wild-type for p53. All liver tumors examined retained the wild-type p53
      allele, indicating that p53 itself may not be a target for radiation-induced
      alteration. Only two p53-deficient mice in the liver tumor group developed thymic
      lymphomas. The p53-deficient mice showed no significant differences in the
      number, size, or growth rate of HCC or in the apparent development of HCC.
      CONCLUSION: These results indicate that p53 deficiency does not enhance the rate
      of development or degree of malignancy of radiation-induced HCC in mice but may
      instead favor the development of multiple primary cancers.

PMID- 10928069
TI  - Construction and in vivo evaluation of an anti-PSA x anti-CD3 bispecific antibody
      for the immunotherapy of prostate cancer.
AB  - BACKGROUND: Cross-linking of tumor antigens with the T-cell associated CD3
      antigen can be effectively achieved by bispecific monoclonal antibodies and lead
      to an increase in antigen-specific cytotoxicity in T cells. Because of the high
      organ specificity of the prostate specific antigen (PSA), a bispecific antibody
      (BiAb) directed against this antigen and CD3 may be a tool for a highly specific
      immune therapy of prostate cancer. METHODS: For generating BiAb, the quadroma
      technique was used. Binding properties both to CD3 and PSA were shown by flow
      cytometry with the CD3 expressing Jurkat cell line and fluorescein-labeled PSA.
      Specific tumor cell lysis was tested with the PSA expressing prostate carcinoma
      cell line LNCaP as target and interleukin-2 activated human peripheral blood
      lymphocytes as effector cells in a chromium-51-release assay. For in vivo
      evaluation of the BiAb, a nude mouse model was used. The mice were inoculated
      with LNCaP prostate carcinoma cells. Animals with growing tumors were treated
      with 100 micrograms BiAb and 5 x 10(6) effector cells. RESULTS: Three stable
      quadromas producing anti-CD3 x anti-PSA BiAb were established. From the culture
      supernatant of one quadroma, BiAb was separated by affinity chromatography and
      tested in vitro and in vivo for its ability to target effector T lymphocytes
      against appropriate tumor cells. In vitro, a specific lysis of PSA expressing
      prostate carcinoma cells was demonstrated. In vivo, a significant reduction in
      tumor growth (p < 0.05) could be shown in nude mice treated with BiAb and
      effector cells as compared to a group treated only with effector cells and an
      untreated control group. CONCLUSION: In the present study, an anti-CD3 x anti-PSA
      BiAb was demonstrated to be effective against prostate carcinoma cells in vitro
      and in vivo. Therefore this BiAb may be a tool for the immunotherapy of prostate
      cancer.

PMID- 10928070
TI  - Immunization with TGF-beta antisense oligonucleotide-modified autologous tumor
      vaccine enhances the antitumor immunity of MBT-2 tumor-bearing mice through
      upregulation of MHC class I and Fas expressions.
AB  - The major purpose of this study was to define if the immunosuppressive effect of
      a transforming growth factor-beta (TGF-beta)-producing autologous tumor vaccine
      can be abrogated and rendered immunogenic by suppressing its TGF-beta secretion
      with antisense strategy. In this study, using a TGF-beta antisense gene modified
      MBT-2 tumor cell line [MBT-2/TGF-beta(-)#3] which we established by ourselves, we
      first demonstrated that the amounts of TGF-beta produced by irradiated (IR) and
      non-irradiated MBT-2/TGF-beta(-) #3 were both significantly decreased when
      detected after in vitro culture for 48 hours. The result of flow cytometry
      analysis reveals that decreased production of TGF-beta led to the increased
      expressions of MHC class I molecule and Fas on the surface of MBT-2 tumor cells.
      This finding may in part explain why the splenocytes obtained from day 17 tumor
      bearing mice (D17TBM) immunized with IRMBT-2/TGF-beta(-)#3 on day 26 expressed a
      higher in vitro cytotoxic activity against MBT-2 tumor cells and hence ensured a
      better survival of D17TBM when they were rechallenged with a two-fold higher
      amount of wild-type MBT-2 tumor cells, 48 hours after surgical removal of the
      primary tumor. Our result implies that decreasing the amount of TGF-beta secreted
      from the autologous tumor vaccine by antisense strategy may significantly improve
      its immunogenicity through up-regulation of both MHC class I and Fas expressions.
      Therefore, this could provide an alternative approach for future active
      immunotherapy.

PMID- 10928071
TI  - 1-Nitropyrene induces elevated expression of oncogenes and tumor suppressor genes
      24 hours after treatment in CBA/Ca mice.
AB  - In an earlier experiment we found that 1-nitropyrene treatment causes an increase
      in the expression of certain onco/suppressor genes in different organs of CBA/Ca
      mice. In order to further study the kinetics and significance of these gene
      expression changes, we determined the effect of 1-nitropyrene treatment on the
      expression of c-myc, p53, Ha-ras, N-ras, and Ki-ras genes, 24 hours after
      treatment. Expression of the ras family did not change during the studied
      interval, while elevated expression of c-myc and p53 genes was observed in the
      spleen, bone marrow and lymph nodes (only c-myc in the latter). The results
      suggest a different pattern for the involvement of the ras genes in 1-nitropyrene
      caused carcinogenesis, and also underlines the differences in the organ
      specificity of chemical carcinogens in humans and in experimental animals. In the
      present study, we also confirmed the in vivo applicability of early gene
      expression changes as biomarkers of carcinogenic exposure.

PMID- 10928072
TI  - An extract of the fern Polypodium leucotomos (Difur) modulates Th1/Th2 cytokines
      balance in vitro and appears to exhibit anti-angiogenic activities in vivo:
      pathogenic relationships and therapeutic implications.
AB  - In the present study we show the capacity of an extract of the fern Polypodium
      leucotomos (PLE) to partially inhibit the production of cytokines showing a Th1
      pattern (IL-2, IFN-gamma and TNF-alpha) in human PHA-stimulated peripheral blood
      mononuclear cells. The percentage of inhibition was 24% for IL-2, 72% for INF
      gamma and 53% for TNF-alpha. With regard to Th2 cytokines, the addition of PLE
      resulted in a significant increase (33%) in IL-10 production. Surprisingly, the
      production of the inflammatory cytokine IL-6 was completely abolished (100%
      inhibition) by PLE at all doses tested. In a second experiment in vivo we show
      that, the topical application of PLE to the skin of hairless albino mice (Skh-1)
      significantly diminished the mast cell infiltrate as well as the number of blood
      vessels triggered by chronic ultraviolet B (UVB) irradiation. These data show
      that PLE moderately inhibits the immunological Th1 responses, thus explaining the
      immunosuppressive as well as the anti-inflammatory and antioxidant activities
      reported in other studies carried out with PLE. The clear inhibitory effect on
      TFN-alpha and IL-6 production strongly suggest that this may be the mechanism by
      which PLE: (a) inhibits angiogenesis in vivo in the mouse model described here,
      and (b) prevents Langerhans' cells depletion caused by solar irradiation in
      humans. Taken together, these data suggest that PLE works through the induction
      of suppressive/anti-inflammatory cytokines such as IL-10 and/or TGF-beta which in
      turn appear to allow the partial deactivation of macrophages or other accessory
      cells. These features suggest that PLE could be useful in the treatment of
      autoaggressive/inflammatory conditions due to an exacerbation of Th1 responses.

PMID- 10928073
TI  - Interaction between hydroquinone and ascorbic acid derivatives: quenching effect
      of organic solvents.
AB  - The interaction between hydroquinone (HQ) and ascorbic acid analogs was
      investigated. Semiquinone radicals (SQ.) generated by HQ were comparably
      scavenged by ascorbic acid, sodium ascorbate and ascorbate 6-palmitate, but much
      less efficiently by ascorbate 2,6-dipalmitate. Organic solvents, such as
      dimethysulfoxide (DMSO) or ethanol, which are utilized for solubilization of
      water-insoluble analogs, ascorbate 6-palmitate and ascorbate 2,6-dipalmitate,
      also scavenged SQ.. DMSO scavenged the SQ. more efficiently than ethanol. This
      suggests the importance of considering such a quenching effect of organic solvent
      in the study of the interaction between HQ and antioxidants. The involvement of
      the ascorbate radical for cytotoxicity induction is discussed.

PMID- 10928074
TI  - Effect of pre-irradiation with low-dose gamma-rays on chemically induced
      hepatotoxicity and glutathione depletion.
AB  - We examined the elevation of glutathione (GSH) level in mouse liver and HepG2
      cells after low-dose gamma-ray irradiation and its inhibitory effect on
      acetaminophen (AAP)- and cumene hydroperoxide (CHP)-induced hepatotoxicity. The
      liver GSH level in male ddY mice increased 2 hours after irradiation with 50 cGy
      of gamma-rays, reached a maximum at around 4 hours and returned almost to the
      control level by 12 hours. The effect of irradiation at 2 hours before AAP
      treatment on the hepatotoxicity was then investigated in terms of glutamic
      pyruvic transaminase (GPT) activity in serum and lipid peroxide (malondialdehyde,
      MDA) content in the liver. GPT activity and MDA level were markedly increased at
      24 hours post-treatment with AAP. Both increases were significantly suppressed by
      a single low-dose pre-irradiation with gamma-rays (50 cGy). The cellular GSH
      level of HepG2 cells increased about 3 hours after exposure to gamma-rays (50
      cGy), peaked at 12 hours and returned almost to the time 0 value by 48 hours post
      irradiation. Exposure of HepG2 cells to CHP induced time- and dose-dependent
      cytotoxicity, as judged from lactate dehydrogenase activity (LDH) released into
      the medium. Pre-irradiation with gamma-rays (50 cGy) at 6 hours before addition
      of 1 mM CHP to the cells significantly suppressed the elevation of LDH activity
      at 24 hours post-treatment. In both cases, the lowered GSH levels induced by AAP
      and CPH appeared to be restored to the control level by pre-irradiation with a
      low dose of gamma-rays. These results suggest that low-dose gamma-ray irradiation
      might be effective for the prevention of hepatotoxicity involving GSH deficiency.

PMID- 10928075
TI  - Mechanisms involved in the elevation of glutathione in RAW 264.7 cells exposed to
      low doses of gamma-rays.
AB  - We examined the mechanisms of the elevation of glutathione level induced in
      macrophage-like RAW 264.7 cells by low doses of gamma-rays. The level increased
      soon after exposure of the cells to 50 cGy of gamma-rays, peaked between 3 hours
      and 6 hours and returned almost to the time 0 value by 24 hours post-irradiation.
      Doses between 25 and 100 cGy significantly increased the glutathione level at 4
      hours post-irradiation. However, there was no significant elevation at doses of
      more than 100 cGy or less than 25 cGy. When the effect of dose rate was examined
      at a constant absorbed dose of 50 cGy, dose rates of more than 50 cGy/minute
      significantly increased the GSH level at 4 hours post-irradiation. It was also
      shown that the elevation of glutathione level in cells irradiated with low doses
      of gamma-rays followed the induction of mRNA coding for gamma-glutamylcysteine
      synthetase (gamma-GCS), a rate-limiting enzyme of the de novo glutathione
      synthesis pathway. When the cells were exposed to the radiation in the presence
      of genistein, calphostin C or nifedipine, the elevations of glutathione and gamma
      GCS mRNA expression were both mostly blocked. EGTA also strongly inhibited these
      elevations. These results suggest that the tyrosine kinase, calcium channel and
      protein kinase C activities play an essential role in the low-dose-radiation
      induced elevation of cellular glutathione.

PMID- 10928076
TI  - -SH groups and glutathione in cancer patient's blood.
AB  - As reported in previous investigations, erythrocytes are the elements of
      peripheral blood most affected by free radical activity in the pathogenesis of
      cancer. In these studies, the level of sulphydrilic groups and reduced
      glutathione were assayed in the erythrocytes and plasma, while their successful
      scavenger activity against cell membrane oxidation and peroxidation has already
      been established. In subjects with cancer, the levels of -SH groups (p < 0.002)
      and reduced glutathione in both plasma and erythrocytes (p < 0.0001) were shown
      be a statistically significantly decreased compared to healthy controls. These
      differences were related to the defence of the hematic tissue against free
      radical activity. A similar pattern has also been reported when studying vitamin
      A and E content in the peripheral blood of cancer patients. The role of oxido
      reduction phenomena in this disease is discussed, as well as the importance of
      reducing the oxido-peroxidation involvement of tissues and cell elements. The
      study of the GSH/GSSG ratio in order to determine the stage of the disease would
      be useful and might represent a systemic marker for cancerous lesions.

PMID- 10928077
TI  - The measurement of AgNORs in human glioma cells.
AB  - Sixty gliomas obtained by neurosurgical resections were examined. Paraffin blocks
      were retrieved from pathological files of the Second Affiliated Hospital in
      Guangzhou Medical College. The methods of argyrophilic technique for AgNORs
      staining, and Image Analysis System for measurement of AgNORs were used. Six
      parameters, which included hcount, count, narea, agnrea, agpern and agperc were
      used to correlated well with histopathological grades (compared grade 2 & 3,
      grade 3 & 4, and grade 2 & 4, respectively). We concluded that AgNORs is useful
      in evaluating proliferative activity and assessing the malignancy of human
      gliomas. It may also be used as a target for anti-neoplastic drugs in the
      treatment of gliomas.

PMID- 10928078
TI  - Pharmacokinetics of hypotonic cisplatin chemotherapy administered into the
      peritoneal and the pleural cavities in experimental model.
AB  - The pharmacokinetics of intraperitoneal (i.p.) and intrapleural (i.pl.) hypotonic
      cisplatin (CDDP) were compared under the same experimental conditions. The same
      dose of CDDP was administered in hypotonic (62 mOsm/L) and isotonic (308 mOsm/L)
      solutions to the peritoneal and pleural cavities of Ehrlich carcinoma cell
      bearing mice. The intracellular amount of platinum increased for more than 60
      minutes after an i.pl. injection of the hypotonic solution of CDDP, whereas it
      increased for up to 30 minutes after an i.p. injection. Although hypotonic
      conditions augmented the amount of platinum taken-up by Ehrlich cells, the amount
      was significantly greater in the pleural cavity than in the peritoneal cavity. In
      Donryu rats, the levels of platinum in the i.p. and i.pl. fluids decreased
      rapidly after injection of hypotonic solution as compared with isotonic solution.
      The extent of this decrease was greater in the peritoneal cavity than in the
      pleural cavity. In the hypotonic condition, the area under the curve of
      concentration versus time (AUC) for platinum of i.pl. fluid was greater than that
      of i.p. fluid. When i.p. and i.pl. hypotonic CDDP were administered, the
      osmolarity of the fluid returned rapidly to the isotonic level, with
      equilibration in 30 or 180 minutes respectively. The lower osmolarity continued
      for a longer duration in the pleural cavity than in the peritoneal cavity. These
      results indicate that the pleural cavity may require a smaller amount of CDDP to
      achieve the same effect on intracellular uptake of platinum than the peritoneal
      cavity.

PMID- 10928079
TI  - CA 19-9 monosialoganglioside content of human colorectal tumor cells correlates
      with tumor cell-induced platelet aggregation.
AB  - BACKGROUND: Gangliosides are involved in tumor cell-induced platelet aggregation
      (TCIPA). CA 19-9 is a monosialoganglioside detected in colon carcinoma cells.
      Therefore, this study was designed to evaluate whether there was any correlation
      between the CA 19-9 monosialoganglioside content and TCIPA. MATERIALS AND
      METHODS: The CA 19-9 content was determined on gangliosidic extracts of human
      colorectal tumor cells (GEO, WiDr, DLD-1, MIP) in comparison with the degree of
      TCIPA. RESULTS: CA 19-9 was detected in all cell lines, except MIP. The mean CA
      19-9 content was 10.2, 30.2 and 82.6 U/microgram of sialic acid for GEO, DLD-1
      and WiDr, respectively. CA 19-9 content directly correlated with TCIPA (p <
      0.0001). Furthermore, incorporation of exogenous gangliosides in GEO cells
      resulted in an increase of CA 19-9 content, paralleled by a concomitant increase
      of TCIPA. CONCLUSIONS: The CA 19-9 monosialoganglioside may be involved in
      platelet/tumor cell interactions, thus playing an important role in the
      haematogenous metastases of colorectal cancer.

PMID- 10928080
TI  - Evaluation of a possible styrene-induced damage to the haematopoietic tissues in
      the rat.
AB  - The aim of this study was to determine a possible risk of malignancies in the
      haematopoietic tissues of rats treated with styrene, either by injection or by
      inhalation. Two experiments were carried out: in the first (acute treatment), 12
      male rats were treated intraperitoneally with different doses of styrene (40
      mg/Kg/2 ml/die and 400 mg/Kg/2 ml/die) for 3 consecutive days. A control group (6
      rats) was administered corn oil 2 ml/kg/die for the same period of time. In the
      second experiment (chronic treatment), 12 male rats were exposed to styrene
      inhalation (300 ppm/6 hour day/5 days a week for 2 weeks) for 3 weeks and
      sacrificed at the end of the experiment or after 3 weeks. The rats treated with
      the highest doses of styrene by injection (400 mg/kg, acute treatment) showed a
      hyperactivity of the erythropoietic series while the granulocytopoietic series
      was at the normal value. The rats exposed to 300 ppm styrene vapour (chronic
      treatment) showed a statistically significant increase in erythropoietic cells
      (basophilic, polychromatophilic and orthochromatic erythroblasts). A temporary
      block of immature cells of the granulocytopoietic series was also evident. These
      results indicate an alteration of the erythropoietic series independently of
      method of administration. However, these findings do not show a possible risk of
      preleukemic or leukemic disorders in rats exposed or treated with styrene.

PMID- 10928081
TI  - p16INK4 gene mutation and allelic loss of chromosome 9p21-22 in Taiwanese
      hepatocellular carcinoma.
AB  - BACKGROUND: The p16INK4 (MTS1/CDNK2A) gene, located on chromosome 9p21, is an
      inhibitor of cyclin-dependent kinase 4. Various data have shown that it is
      frequently inactivated in several types of cell lines and primary human cancers.
      MATERIALS AND METHODS: Thirty cases with hepatocellular carcinoma were studied
      for possible p16INK4 gene mutation in Taiwan. Homozygous deletion was determined
      using polymerase chain reaction (PCR). The p16INK4 gene mutation was first
      screened by single strand conformation polymorphism, then direct DNA sequencing
      was performed on the cases with mobility shifts. Deletion mapping of chromosome
      9p21-22 was also carried out with two polymorphic microsatellite markers (D9S925
      and D9S168) using PCR. RESULTS: One of the 30 cases had homozygous deletion at
      exon 3 of the p16INK4 gene. Another tumor had altered electrophoresed mobility in
      exon 2 with G to T transversion in the first nucleotide of codon 61 by direct
      sequencing causing a stop codon (GAG-->TAG). At the D9S925 and D9S168 loci, six
      out of 24 (25%) and three out of 19 (16%) informative cases showed loss of
      heterozygosity, respectively. CONCLUSION: Point mutation and homozygous deletion
      of the p16INK4 gene are present in a subset of hepatocellular carcinomas in
      Taiwan. The patterns of the p16INK4 gene alteration are, however, different from
      those from other regions. In addition, allelic loss on chromosome 9p21-22 is not
      an uncommon event in hepatocellular carcinomas. Therefore, the significance of
      chromosome 9p loss deserves to be extensively investigated.

PMID- 10928082
TI  - Effects of cyclocreatine in rat hepatocarcinogenesis model.
AB  - Cyclocreatine (CCr), a substrate analogue of creatine kinase (CK: EC 2.7.3.2.),
      exhibits anti-tumor activity in vitro and in vivo. We examined the effects of CCr
      on the hepatocarcinogenesis of F344 rats caused by treatment with
      diethylnitrosamine (DEN), partial hepatectomy (PH) or 2-acetylaminofluorene (2
      AAF). The rats were given a single intraperitoneal injection of 200 mg of DEN per
      kg in 0.85% NaCl solution at four weeks of age. Two weeks later they were divided
      into two groups. One group was continuously fed a commercial powder diet
      containing 0.02% 2-AAF for 12 weeks and the other was continuously fed a
      commercial powder diet containing 1% CCr plus 0.02% 2-AAF for 12 weeks. A third
      group of rats as a control was given only a normal powder diet for 12 weeks. All
      the groups were subjected to a two-thirds partial hepatectomy (PH) at 3 weeks
      under avertin anesthesia. To elucidate the inhibitory effect of CCr on chemical
      induced hepatocarcinogenesis, we examined not only the distribution of
      glutathione-S-transferase placental form (GST-P) a marker used for tumorigenesis,
      but also the inhibition of the degree of apoptosis. The number (No./cm2) and area
      (mm2/cm2) of GST-P positive liver foci were significantly lower in the 2-AAF +
      CCr treated when compared to the group treated with 2-AAF only. Our data suggest
      that CCr inhibits the degrees of GST-P-positive cells and apoptosis and is active
      against hepatocarcinogenesis in rat models. This result points out the unique
      nature of an anticancer agent that inhibits progression of chemically induced
      hepatocarcinogenesis of rats.

PMID- 10928083
TI  - Beware of contaminating mouse cells in human xenografts from nude mice.
AB  - Human tumor xenografts in nude mice are widely utilized model system for the
      transplantation of human surgical specimens and human established cell lines.
      Gene expression studies are often carried out in these model systems. With an
      increasing use of PCR based analyses, the extreme sensitivity of this technique
      poses a serious challenge with regards to the extent of contaminating host mouse
      cells in the human tumor xenografts. These xenografts are never free of host cell
      contamination. We detected mouse estrogen receptor expression in several human
      tumor xenografts using RT-PCR demonstrating that precaution is necessary when
      utilizing PCR based analyses in human tumor xenografts. A cytologically based
      methodology which distinguishes human versus mouse cells will be more suitable
      for ER expression studies using human xenograft models. Both (1) in situ
      hybridization using human probe and (2) immunocytochemistry using a monoclonal
      antibody directed against human cytokeratin have been used successfully to
      distinguish human cells versus host mouse cells in human xenografts in nude mice.
      Immunostaining of ER can then be utilized to determine the expression pattern of
      ER in the transplanted human cells.

PMID- 10928084
TI  - Helicobacter pylori-induced hyperproliferation: relevance for gastric cancer
      development in connection with mutagenic factors.
AB  - AIMS: Current data on Helicobacter pylori induced regenerative hyperproliferation
      of the antral gastric mucosa and significance in cancer development are still
      under discussion and investigation. An improved method for evaluation of the
      regeneratory process in antral mucosa is introduced and compared with the
      conventional method used for determination of proliferating cells in
      perpendicular sections of the gastric mucosa. METHODS: Using a combination of
      immunohistochemistry and PAS-staining the expression of Ki-67 (MiB1)
      proliferation associated antigen was analyzed in 50 Helicobacter pylori (Hp)
      positive and 35 negative biopsies of the gastric antrum. PAS-staining was
      performed to identify the proliferative zone of the antral gastric glands. The
      degree of inflammation was evaluated by grades on routinely H & E-stained slides.
      RESULTS: Proliferative activity is significantly increased in Hp-positive cases
      (p = 0.00095) compared to negative ones. By using the conventionally applied
      proliferation index, every nucleus has to be counted and the proliferation zone
      is identified by at least one positive stained nucleus. The method presented here
      seems to be easier because the proliferative zone is clearly identified by PAS
      staining of neutral glycoproteins characteristic for the proliferation zone of
      antral glands. The density of labeled nuclei is determined and is expressed as a
      proliferation factor. This factor gives more distinct values, is easier to
      evaluate and shows a better correlation with the helicobacter status and the
      degree of inflammation. These results are discussed in relation to the data from
      the literature and with a view to other relevant factors in the course of
      carcinogenesis, such as growth factors, mainly EGF, p53 mutation and role of
      apoptosis, genetic instability and local production of oxidants. CONCLUSION:
      Helicobacter pylori induces an increase of regenerative proliferation activity.
      Under these conditions the chance of mutation is increased and time for DNA
      repair reduced. This could be at least a part of multiple step carcinogenesis.
      The newly introduced combination of staining procedures (PAS/MiBI) allows a more
      differentiated evaluation of the proliferation zone and its widening. This method
      can be more easily handled in follow-up studies than the method using
      perpendicular sections because in this method heavy irregularities of gland
      pattern induced by accompanying inflammatory processes considerably hinder
      evaluation.

PMID- 10928085
TI  - Synergistic down-regulation of telomerase activity and hTERT mRNA expression by
      combination of retinoic acid and GM-CSF in human myeloblastic leukemia ML-1
      cells.
AB  - Telomerase, the enzyme that synthesizes telomeric DNA, is repressed in normal
      human somatic cells but is activated with in vitro immortalization or during
      tumorigenesis. In this study, we investigated telomerase activity and expression
      of genes involved in telomerase activity in human myeloblastic leukemia ML-1
      cells, differentiated synergistically by treatment with all-trans retinoic acid
      (ATRA) and granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF
      alone was not effective in changing telomerase activity whilst ATRA alone
      slightly decreased the activity. A combination of ATRA and GM-CSF remarkably
      reduced telomerase activity. We also detected remarkable suppression of hTERT
      mRNA expression in ML-1 cells treated with ATRA and GM-CSF. These results
      indicate that a synergistic down-regulation of telomerase activity and hTERT mRNA
      expression is induced by treatment with ATRA and GM-CSF in ML-1 cells.

PMID- 10928086
TI  - Cationic liposome-enhanced adenoviral gene transfer in a murine head and neck
      cancer model.
AB  - The effect of combining adenoviral vector and cationic liposomes on the
      efficiency of gene transfer to head and neck tumor cells was investigated. Two
      human and two murine cell lines were used for the screening of gene transfer
      efficiency using an adenoviral vector. Cationic liposome-enhanced gene transfer
      was checked using a murine squamous carcinoma cell line, SCCVII/SF. A
      considerable difference in the efficiency of gene transduction was observed among
      the cell lines. The combination of DOSPER and adenoviral vector containing human
      alkaline phosphatase showed a remarkable enhancing effect in gene transfer in
      vitro and in vivo, compared to the adenovirus alone or control groups. With an
      improvement in the efficiency of gene transfer, it may be possible not only to
      enhance the expression of transduced genes, but also to deliver a smaller amount
      of virus, as a result, reducing toxicity and the immune response against
      adenovirus.

PMID- 10928087
TI  - Effects of cyclic plasma perfusion on adipocyte apoptosis and lipolytic activity
      in VX2 carcinoma-bearing rabbits.
AB  - BACKGROUND: In an animal model we found that total body fat (TBF) decreased with
      progression of tumors, but that it rebounded after cyclic plasma perfusion (CPP).
      In this study, we investigated changes in adipocyte apoptosis and serum lipolytic
      activity (LA) after CPP. MATERIALS AND METHODS: TBF, LA, and adipocyte apoptotic
      index (AAI) in VX2 carcinoma-bearing rabbits were measured every ten days after
      implantation. CPP was performed every 5 days from post-implantation day (PID) 14.
      RESULTS: TBF decreased as the days passed and reached 43.2 +/- 10.0% on PID 50 in
      the non-CPP group, while it decreased 22.7 +/- 8.8% in the CPP group. LA on PID
      50 was 17.8 +/- 14.0, 33.2 +/- 6.3 mumol glycerol/10(5) adipocytes in the non-CPP
      group, while LA did not increase in the CPP group. AAI was 28.8 +/- 16.4, 27.8 +/
      17.7, 10.3 +/- 9.9 and 0.4 +/- 1.1 on PID 10, 20, 30, and 40, respectively, in
      the non-CPP group. No change was noted in AAI after CPP. CONCLUSIONS: CPP removed
      a humoral factor that possesses TBF-decreasing LA, but it did not suppress
      adipocyte apoptosis.

PMID- 10928088
TI  - Flow cytometric evidence of apoptosis in human pancreatic cancer xenografts
      treated with Sandostatin (octreotide).
AB  - BACKGROUND: The antiproliferative effect of octreotide (Sandostatin) is partly
      attributed to induction of apoptosis in the given tumors. In this work, apoptosis
      was assessed in human pancreatic carcinoma xenografts after a 4-week high-dose
      Sandostatin treatment. MATERIALS AND METHODS: Subcutaneously growing human
      pancreatic cancer xenografts (PZX-5) in immunosuppressed mice were treated with
      500 micrograms/kgb.w. Sandostatin twice a day i.p. for 4 weeks. Apoptosis was
      evaluated by means of conventional histology, Apoptag-immunohistochemistry and
      flow cytometry. RESULTS: The Sandostatin-treatment resulted in a decreased tumor
      volume in 9 out of 16 animals. Immunohistochemical detection of apoptosis by
      Apoptag revealed a 75-fold increase of the positively stained tumorous nuclei
      (210.9 +/- 53.9 per square mm) versus nontreated tumors (2.8 +/- 0.5 per square
      mm). The sub-G1 fraction was 3.61 +/- 0.4% in untreated samples while it doubled
      after treatment (p < 0.001). CONCLUSION: A 4-week octreotide (Sandostatin)
      treatment induced significantly increased apoptosis in human pancreatic carcinoma
      xenografts evidenced by morphological studies and Apoptag-immunohistochemistry,
      and these results were clearly reinforced by flow cytometry.

PMID- 10928089
TI  - In vitro effect of hyperthermia on natural cell-mediated cytotoxicity.
AB  - It is well known that hyperthermia (HY), which is used for the treatment of
      cancer, depresses natural cell-mediated immunity in vitro. Experiments were
      performed to confirm the inhibitory effect of HY (42 degrees C for 1 hour) on
      natural killer (NK) activity and to evaluate the influence of HY on the
      generation and cytotoxic activity of interleukin-2 (IL-2)-activated NK cells.
      Additional experiments were also carried out to evaluate the effect of a
      simultaneous exposure of effector and target cells to HY. The results showed that
      HY profoundly reduced the lytic activity of NK cells and demonstrated that this
      inhibition was transient and not due to an apoptosis-induced reduction of the
      number of effector cells. Moreover, the exposure of mononuclear cells to HY
      before IL-2 stimulation did not affect the generation of IL-2-activated NK cells,
      whereas, the hyperthermic treatment of IL-2-activated NK cells produced a marked
      reduction of their cytotoxic activity. The results also showed that the
      simultaneous exposure of effector and target cells to HY, during the cytotoxicity
      assay, produced a marked reduction of lytic activity of NK and IL-2-activated NK
      cells, and that this impairment was specific for effector cells. In this context,
      heat-exposure of target cells alone, did not substantially modify their
      susceptibility to lysis induced by either NK or IL-2-activated NK cells. These
      results add further evidence of HY-induced inhibition of natural cell-mediated
      immunity, and suggest that, in the course of therapeutic HY, immune response
      could be significantly altered.

PMID- 10928090
TI  - Toxic proteins from European mistletoe (Viscum album L.): increase of
      intracellular IL-4 but decrease of IFN-gamma in apoptotic cells.
AB  - BACKGROUND: Mistletoe lectins (ML), the major biologically active components of
      mistletoe extracts, which are used for adjuvant cancer therapy, induce apoptosis
      in lymphocytes and tumor cells. In addition, ML at toxic concentrations induce
      the release of cytokines, but it remains unclear as to whether dying or activated
      cells are responsible. MATERIALS AND METHODS: By flow cytometry, expression of
      IFN-gamma, IL-4, apoptosis marker Apo2.7 and anti-apoptotic Bcl-2 proteins were
      analyzed in response to ML or viscotoxins (VT) in PBMC from controls and
      plasmocytoma cells (U-266). RESULTS: While ML inhibited PMA/Ca-ionophore/monensin
      co-stimulated IFN-gamma production, they increased IL-4 expression in CD8+ and
      CD4+ T-cells. Thereby, IL-4 was mainly expressed in apoptotic cells with a low
      level of Bcl-2 proteins. In contrast, the cell membrane permeabilising VT induced
      complete loss of Bcl-2 proteins but did not stimulate IL-4 production within 24
      hours, indicating that IL-4 expression is related to apoptosis but not to
      necrosis. CONCLUSION: Despite the role of IL-4 during activation of type2 T
      helper cells, IL-4 expression may play an important yet undefined role during
      apoptosis of normal and tumor cells.

PMID- 10928091
TI  - The expression of angiogenin in tissue samples of different brain tumours and
      cultured glioma cells.
AB  - BACKGROUND: As a potential angiogenetic factor the 14.1 kDa polypeptide
      angiogenin induces neovascularisation. MATERIALS AND METHODS: We investigated the
      angiogenin expression by immunoblotting and an ELISA in 60 tissue specimens (40
      gliomas, 20 other intracranial tumours), in 22 glioma cell cultures and in 4
      supernantants of cultivated glioblastoma cells. RESULTS: We could show that
      angiogenin is detectable in different kinds of intracranial tumours with the
      highest amount in meningiomas and the lowest amount in low grade astrocytomas. In
      tissue specimens, a significantly higher angiogenin expression was measured in
      meningiomas compared to gliomas and metastases. Angiogenin could be detected in
      primary cultivated glioma cells, but not in the permanent cell lines. There was a
      significant correlation to the malignancy within the gliomas with an increase of
      angiogenin concentration according to the higher grade of malignancy.
      CONCLUSIONS: Our data suggest that angiogenin may contribute to the malignant
      transformation of gliomas and could perhaps advise that the physiological role of
      angiogenin is not restricted exclusively to angiogenesis. Based on these findings
      the clinical importance of angiogenin for therapeutic decisions in malignant
      brain tumours remains unclear and further analyses on m-RNA-levels are required.

PMID- 10928092
TI  - Prognostic significance of newly defined ploidy related parameters in melanoma.
AB  - 5c exceeding rate is the parameter, most frequently showing prognostic impact.
      The CAS200 image analyzer makes possible the measurement of additional parameters
      defining single subfractions of cells, as for example the ratios of diploid,
      aneuploid, tetraploid, octaploid and 16-ploid cells. The main objective of this
      study was to define the prognostic significance of these new parameters in 106
      primary melanomas with known survival time. 29 out of 106 melanomas were euploid.
      77 out of 106 showed an aneuploid histogram. Multivariate analysis with Cox
      regression demonstrated that the percentage of aneuploid cells between 2c and 4c
      and the percentage of aneuploid cells between 4c and 8c, but not 5c exceeding
      rate, were able to influence survival time.

PMID- 10928093
TI  - Effects of genistein and 2-methoxyestradiol on matrix metalloproteinases and
      their inhibitors secreted by Ehrlich ascites tumor cells.
AB  - BACKGROUND: Ehrlich ascites tumor is an experimental tumor model very suitable
      for performing comparative studies relating its growth in vitro and in vivo. We
      used this tumor model to study the potential modulatory effects of genistein and
      2-methoxyestradiol, two anti-angiogenic compounds, on the proteolytic balance
      MMP/TIMP. Ehrlich cells grown in vitro secreted MMP-9, MMP-2 and two TIMPs; the
      treatment with either of the anti-angiogenic compounds here tested stimulated all
      these activities, but the increase in TIMPs activities of genistein-treated cells
      were higher than those of MMPs, thus inducing a decrease in the proteolytic
      balance. On the other hand, Ehrlich cells growing in vivo did not produce any
      detectable TIMP activity, but accumulated MMP-9 and MMP-2 during tumor growth.
      Both compounds induced significant decrease of MMPs activity when tumor cells
      were actively proliferating. It was concluded that both genistein and 2
      methoxyestradiol could shift the proteolytic balance MMP/TIMP towards
      antiproteolysis in media or ascitic fluid conditioned by actively growing Ehrlich
      cells.

PMID- 10928094
TI  - The prognostic value of the presence of mutations at the codons 12, 13, 61 of K
      ras oncogene in colorectal cancer.
AB  - The predictive and prognostic value of the c-K-ras mutation is still unequivocal
      despite extensive and intensive studies. Investigation of the occurrence of
      mutations in 88 colorectal cancer patients' specimens using the polymerase chain
      reaction (PCR) is reported: age: 61.9 years (27-80), gender: 48 male, 42 female,
      Dukes' stages: 43 at B, 35 at C, 10 at D, primary of tumour: 52 colon, 36 rectal
      adenocarcinoma. Mutation of one of the three ras-codons was detectable in the 54
      cases, more frequently at the Dukes' stage C (p < 0.05). The ras-mutation
      correlated to a more elevated death-rate in the Dukes' B and C stages (p < 0.01).
      Mean survival time and time to progression were significantly longer at the
      Dukes' stage B if mutation was not detected (p < 0.01). The genetic alteration
      occurred significantly more frequently at tumours of the right-side colon, than
      the left side (p < 0.02) or rectum (p < 0.05). However, in the age group of 41-50
      years, it was more significantly identified in the cases of rectal cancer (p <
      0.01). At the age of 51-60 years mutations were detected in men at a higher rate
      (p < 0.05). The mutation of the codon 13 appeared more frequently in the cases of
      local recurrences (p < 0.05). The occurrence of the ras-oncogene is a sign of an
      extremely malignant potential of tumour. This fact manifested itself in the time
      to progression and mean survival time of patients at the same clinical or
      pathological stage. The higher frequency of genetic alterations at the proximal
      colon may be the reason for more unfavourable prognosis of the disease localised
      to this site. Reconstructing the molecular events, the presence of the ras
      mutation proved to be an important element for prognosis of the disease and
      should be a basis of potentially individualised therapeutic intervention.

PMID- 10928095
TI  - Cyclosporine A inhibition of prolactin-dependent up-regulation of BRCA1 protein
      expression in human breast cell lines.
AB  - BACKGROUND: Previously, we reported experimental evidence that BRCA1, breast and
      ovarian cancer susceptibility gene is up-regulated in response to Prolactin
      stimulation. In this work, we studied the effects of Cyclosporine A and the
      competition with Prolactin on BRCA1 protein expression in vitro. METHODS: The
      expression of BRCA1 was monitored in a human breast cancer cell line (MCF7) by
      comparison with a normal breast epithelial one (MCF10a) treated with Cyclosporine
      A and ovine Prolactin. The amount of BRCA1 protein expression was quantified
      using a strategy of two successive affinity perfusion chromatographies. RESULTS
      AND CONCLUSION: We showed that Prolactin in presence of Cyclosporine A has no
      effect on BRCA1 protein expression in human breast cell lines. This emphasized
      the hypothesis that BRCA1 may be stimulated by Prolactin.

PMID- 10928096
TI  - Glutathione S-transferases and iododeoxyuridine labelling index during
      chemotherapy of gastric cancer.
AB  - BACKGROUND: Resistance to chemotherapeutic agents is a major problem in the
      treatment of patients with gastric cancer. Many factors may play a role in the
      resistance to cytotoxic drugs. The purpose of this study was to investigate the
      significance of glutathione (GSH), glutathione S-transferases (GSTs) and cell
      proliferation as parameters for response and resistance to chemotherapy in
      patients with gastric cancer. METHODS: In endoscopic biopsies of normal and
      malignant gastric tissue from 15 patients with gastric cancer treated by
      chemotherapy, the GSH content, GST activity and levels of GST Alpha, Mu and Pi
      isoenzymes were determined before the start of chemotherapy and after 2 and 6
      cycles. Furthermore, cell proliferation was determined in these biopsies after in
      vivo Iododeoxyuridine (IdU) labelling. RESULTS: None of the above mentioned
      parameters were predictive for response to chemotherapy. After 2 courses of
      chemotherapy there was an increase of median GSH content (367%) in three patients
      with partial response (PR), whereas there was a decrease (43%) in five patients
      with progressive disease (PD) (p < 0.05). Median GST activity increased (257%) in
      patients with PR and declined (31%) in patients with PD (p < 0.05). GST Pi showed
      a median increase of 326% in responding patients and a 59% decrease in
      progressive patients (p < 0.05). There were no significant changes in GST Alpha
      and Mu. In seven patients with stable disease (SD) there were no significant
      changes in GSH/GST parameters. CONCLUSION: GSH/GST parameters and IdU labelling
      index determined before the start of chemotherapy were not predictive for
      response to that chemotherapy. However, the differences of GSH and GST parameters
      between responding and progressive patients suggests a role for the GSH/GST
      system in the susceptibility of gastric tumor cells to chemotherapy.

PMID- 10928097
TI  - Influence of co-medicated drugs on the biotransformation of thioTEPA to TEPA and
      thioTEPA-mercapturate.
AB  - BACKGROUND: The combination of cyclophosphamide, thioTEPA and carboplatin is used
      in our Institute for the treatment of breast or germ cell cancer. ThioTEPA
      inhibits the bioactivation of cyclophosphamide, and platinum drugs are known to
      interfere with the hepatic metabolism of several anticancer drugs. Of the co
      administered drugs to prevent unwanted side effects, some are enzyme inducers,
      cytochrome P450 inhibitors or substrates. The aim of this study was to
      investigate the influence of co-medicated drugs on the biotransformation of
      thioTEPA. METHODS: The possible inhibition of the metabolism of thioTEPA to TEPA
      was investigated in human microsomes. Influences on the conversion of thioTEPA to
      monoglutathionylthioTEPA, was studied by the incubation of thioTEPA with
      glutathione and glutathione S-transferase. RESULTS: No inhibition of the
      metabolism of thioTEPA to form TEPA was observed for cyclophosphamide and
      carboplatin, or any other co-medicated drug (ciproflocaxin, amphotericin B,
      itraconazol, fluconazol, ondansetron, dexamethasone, granisetron, aciclovir,
      ranitidine, lorazepam). The conversion of thioTEPA to monoglutathionylthioTEPA
      was inhibited by cyclophosphamide, itraconazol, amphotericin B and ondansetron
      with IC50 values of 58, 256, 55 and 40 mM, respectively, which are far higher
      than therapeutic drug levels. CONCLUSION: No clinically relevant drug-drug
      interactions occur in the CTC regimen as applied in our Institute.

PMID- 10928098
TI  - Synergistic antitumor effects of a selective proteasome inhibitor and TNF in
      mice.
AB  - The ubiquitin-proteasome pathway is becoming an attractive target in cancer
      therapy. The inhibitors of proteasomes have recently been shown to induce
      apoptosis of tumor cells in vitro and to exert significant antitumor effects in
      murine tumor models in vivo. Proteasome inhibitors, also prevent NF-kappa B
      activation. Since this transcription factor is responsible for counteracting
      apoptosis induced by numerous agents, and proteasome inhibitors have already
      proved efficacious in increasing the proapoptotic activity of TNF in vitro, we
      decided to evaluate the antitumor effects of the combined PSI and TNF treatment
      against a murine C-26 carcinoma. Both agents separately exerted moderate
      antitumor efficacy. However, their combination proved to exert dramatic antitumor
      activity with retardation of tumor growth and prolongation of mice survival time.
      Moreover, 50% of the mice were completely cured by this drug combination.
      Unexpectedly, there was no potentiation of the cytostatic/cytotoxic effects of
      these drugs in in vitro assays which argues against the direct influence on C-26
      cells. Similarly, the influence of these drugs on tumor induced angiogenesis does
      not seem to explain the observed antitumor effects. Further studies are necessary
      to explain the striking antitumor effects of the PSI and TNF combination.

PMID- 10928099
TI  - Synthesis of 4-(acylaminomethyl)benzamides and their evaluation as potential
      anticancer agents.
AB  - 4-(acylaminomethyl)benzamides were prepared in two steps from 4
      aminomethylbenzoic acid and assayed in the NCl's primary anti-cancer screen.
      Eight out of 34 compounds showed interesting antiproliferative activity. From
      these compounds, three were selected for further in vivo testing. In addition,
      all the compounds were tested against farnesyltransferase and the cell cycle
      regulating enzymes cdc2 kinase and cdc25 phosphatase. The compounds proved
      inactive in these assays, as were some selected compounds in an assay searching
      for possible interference with the ras/raf interaction in a yeast two-hybrid
      system.

PMID- 10928100
TI  - Relationship between GAGE-1/-2 expression, EBV infection and interferon-gamma
      expression in undifferentiated carcinoma of nasopharyngeal type.
AB  - GAGE-1/-2 proteins are novel tumour markers, functionally related to tumour
      rejection. The objective of the present study was to identify the existence of a
      relationship between GAGE-1/-2 expression, Epstein Barr Virus (EBV) infection and
      viral infection-induced cytokine expression in cultivated tumour cells and
      archival specimens of undifferentiated carcinoma of nasopharyngeal type (UCNT).
      PCR and in situ hybridization techniques were employed. In cultivated UCNT cells,
      interferon-gamma (IFN-gamma) induced synthesis of GAGE-1/-2 mRNA. In archival
      tumour specimens (n = 10) however, GAGE-1/-2 gene expression was detected in only
      3/8 cases with coincident EBV infection and IFN-gamma expression. In conclusion,
      EBV infection appears to induce IFN-gamma gene expression in most tumors, but
      GAGE-1/-2 expression in only some tumours. The role of IFN-gamma and other
      factors in triggering GAGE-1/-2 gene activation must be elucidated further. The
      relevance of GAGE-1/-2 gene expression and its detection by PCR for future
      immunotherapy is discussed.

PMID- 10928101
TI  - The inhibitory effect of curcumin, genistein, quercetin and cisplatin on the
      growth of oral cancer cells in vitro.
AB  - Epidemiological evidence indicates that plant derived flavonoids and other
      phenolic antioxidants protect against heart disease and cancer. In the current
      investigation utilizing human oral squamous carcinoma cell line (SCC-25), we have
      evaluated the potency of three different plant phenolics, viz., curcumin,
      genistein and quercetin in comparison with that of cisplatin on growth and
      proliferation of SCC-25. Test agents were dissolved in DMSO and incubated in
      triplicates in 25 cm2 flasks in DMEM- HAM's F-12 (50:50)supplemented with 10%
      calf serum and antibiotics in an atmosphere 5% CO2 in air for 72 hours cell
      growth was determined by counting the number of cells in a hemocytometer. Cell
      proliferation was determined by measuring DNA synthesis by the incorporation of
      [3H]-thymidine in nuclear DNA. Cisplatin (0.1, 1.0, 10.0 microM) and curcumin
      (0.1, 1.0, 10.0 microM) induced significant dose-dependent inhibition in both
      cell growth as well as cell proliferation. Genistein and quercetin (1.0, 10.0,
      100.0 microM) had biphasic effect, depending on their concentrations, on cell
      growth as well as cell proliferation. Based on these findings, it is concluded
      that curcumin is considerably more potent than genistein and quercetin, but
      cisplatin is five fold more potent than curcumin in inhibition of growth and DNA
      synthesis in SCC-25.

PMID- 10928102
TI  - Evaluation of the antitumor activity of 1-(3-C-ethynyl-beta-D-ribofuranosyl)
      (PJ272), a recent ribonucleoside analogue.
AB  - The antiproliferative properties of a new ribonucleoside derivative, 1-(3'-C
      ethynyl-beta-D-ribofuranosyl)uracil (PJ 272) that we synthesized a few years ago,
      were investigated in vitro on a variety of tumor cell lines from human and murine
      origins and in vivo, in tumor bearing mice. Using the 3(4,5-dimethylthiazol-2-yl)
      2,5-diphenyltetrazolium bromide (MTT) assay, we showed the ability of this
      compound to depress, at nanomolar concentrations, the growth of leukemia and
      lymphoma cultured cells. In 7 out of 8 tumor cell lines tested concentration of
      50% inhibition (IC50) was found to be less than 25 nM. PJ 272 was also shown to
      present the same cytotoxicity against K562 Adriamycin-resistant cell line, which
      express a multi-drug resistance (MDR) phenotype, and its Adriamycin-sensitive
      parent cell line. Moreover, when injected intraperitoneally at 20 mg/kg every
      three days, PJ 272 was found to significantly increase the survival rate (T/C =
      149%) of DBA/2 mice injected intraperitoneally with L1210 leukemic cells. Taken
      together, these results suggest that PJ 272 could be considered as a potentially
      very active drug against lymphoma and leukemia.

PMID- 10928103
TI  - Overexpression of NM23-1 enhances responsiveness of IMR-32 human neuroblastoma
      cells to differentiation stimuli.
AB  - BACKGROUND: Aggressiveness of neuroblastoma is associated with increased
      expression of the putative metastasis suppressor genes, nm23-1 and nm23-2. These
      genes encode nucleoside diphosphate kinases A and B that form free or bound homo-
      and heteromers, which are distributed between soluble and particulate fractions
      of cells and display catalytic and non-catalytic activities. MATERIALS AND
      METHODS: In order to establish which forms and activities of nm23 proteins are
      operative in neuroblastoma we stably transfected IMR-32 human neuroblastoma cells
      with constructs encoding wild type and catalytically inactive nm23-1 and nm23-2
      proteins. RESULTS: Overexpression of wild type nm23-1 proteins stimulated
      spontaneous neurite outgrowth and enhanced differentiation in response to serum
      starvation and retinoic acid. In contrast, overexpression of the catalytically
      inactive nm23-1T mutant enhanced TPA-mediated inhibition of differentiation.
      CONCLUSION: Our findings suggest that differentiation associated functions of
      nm23 proteins in IMR-32 neuroblastoma cells are carried out by bound nm23-1
      proteins docked in a limited number of nm23-1 specific sites.

PMID- 10928104
TI  - Methylenetetrahydrofolate reductase (MTHFR) polymorphism increases the risk of
      cervical intraepithelial neoplasia.
AB  - Although cervical cancer is a common female cancer, little attention has been
      given to genetic susceptibility factors. The present case-control study was
      undertaken to examine MTHFR polymorphism as a potential molecular marker of
      cervical intraepithelial neoplasia (CIN) susceptibility and to relate the
      findings to smoking, HPV infection, ethnicity, parity and oral contraceptive use,
      which are known risk factors for cervical cancer. A base change from C to T at
      the nucleotide position 677 of the MTHFR gene results in substitution of valine
      (GTC) for alanine (GCC). The homozygous normal (Ala/Ala), homozygous mutant
      (Val/Val), and heterozygous mutant (Ala/Val) genotypes for the MTHFR gene were
      determined in cervical tissues of 64 cases of CIN lesions and 31 controls. The
      genotype frequencies of both Val/Val (17%) and Ala/Val (56%) were significantly
      higher in subjects with CIN lesions compared to controls with Val/Val (10%) and
      Ala/Val (39%), (trend p = 0.03). The results suggested a significantly increased
      CIN risk with an alanine to valine substitution at amino acid 223 of MTHFR with
      an odds ratio of 2.9 (95% confidence interval: 1.2-7.9, p = 0.02). Age,
      ethnicity, smoking and oral contraceptive use were weakly and nonsignificantly
      associated with CIN risk. HPV infection was associated with a statistically
      nonsignificant threefold increase in CIN risk. Parity and MTHFR genotype
      displayed a strong interaction. Neither nulliparous women with MTHFR polymorphism
      nor parous women without the polymorphism were at higher risk than women who did
      not have children and were MTHFR homozygous normal (the reference category).
      Women with mutant MTHFR genotype who had children, however, showed a
      significantly higher risk of CIN, with an odds ratio of 23 (95% confidence
      interval: 2.3-225) as compared to the reference category. No other factors
      displayed such a strong pattern of interaction. Since MTHFR polymorphism and
      pregnancy increases folate requirements and can impair folate status, this
      association could reflect an inadequate response of mutant MTHFR genotype
      carriers to the increased demand for folate imposed by pregnancy. Tissue folate
      deficiency, in turn, could increase the risk of CIN in the affected women.

PMID- 10928105
TI  - Controversies on the prognostic significance of tumor infiltrating leukocytes in
      solid human tumors.
AB  - We have performed immunophenotypical (IP) analyses of tumor infiltrating
      leukocytes (TIL) in both childhood brain tumors (medulloblastomas[MEDs]/primitive
      neuroectodermal tumors [PNETs] and astrocytomas [ASTRs]) and malignant melanomas
      (both primary and metastatic) employing a well-characterized library of
      monoclonal antibodies (MoABs) directed against leukocyte
      differentiation/activation associated antigens. The antigens were detected by an
      indirect, biotinstreptavidin conjugated alkaline phosphatase (AP)
      immunocytochemical technique. Our systematic cell-surface antigen expression
      profile analysis of 76 primary childhood brain tumors (34 MEDs/PNETs and 42
      ASTRs) identified CD8+ CTL in 58/76 brain tumors. CD4+, MHC class II restricted
      helper lymphocytes were present in 65/76 brain tumors and represented 1-10% of
      the observed cells. Macrophages were present in 74/76 childhood brain tumor cases
      observed by us. Leukocyte common antigen (LCA) expression was demonstrated in all
      76 brain tumors studied. MoAB UJ 308 detected the presence of premyelocytes and
      mature granulocytes in 60/76 brain tumors. They were localized perivascularly,
      within the tumor tissue, or close to necrotic regions. Natural killer (NK) cells
      were not defined in the childhood brain tumors observed in this study. The IP
      characteristics of the heterogeneous leukocytic infiltrate of 30 primary (PMs)
      and 10 metastatic melanomas (MMs) was also investigated by us. We established the
      presence of some type of melanoma infiltrating host's immunological effector
      cells in all 40 observed melanoma cases. More specifically, we found NK cells,
      macrophages and granulocytes in 30/30 PMs and 10/10 MMs. These effector cells
      represented the vast majority (> 80%) of the melanoma infiltrating
      immunocompetent cells. T lymphocytes were observed in 20/30 PMs and 6/10 MMs, but
      their numbers represented only between 5% to 10% of the heterogeneous leukocytic
      infiltrate. B cells were found in 22/30 PMs and 8/10 MMs, their numbers
      representing less than 5%. Presence of cells of the dendritic reticulum, involved
      in antigen presentation was not determined in any of the observed PMs and MMs.
      The notion that infiltration of the neoplastically transformed mass of cells by
      TIL is always a prognostically positive phenomenon has changed in recent years as
      research on extracellular matrix remodeling and angiogenesis have identified
      numerous secreted factors which are common to both neoplastically transformed
      cells and infiltrating leukocytes.

PMID- 10928106
TI  - Immunocytochemical detection of the homeobox B3, B4, and C6 gene products in
      childhood medulloblastomas/primitive neuroectodermal tumors.
AB  - The homeobox 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. It has been shown that HOX-B3 and
      HOX-B4 are preferentially expressed in primitive CD34+, lineage-committed
      hematopoietic stem cells (HSCs) in human bone marrow. HOX-B3 overexpression in
      HSCs causes defective lymphoid development and progressive myeloproliferation,
      while HOX-B4 leads to selective expansion of HSCs without altering their
      differentiation. The HOX-C6 gene product leads to cell differentiation in
      neuroblastomas, while also being associated with the neoplastically transformed
      mammary cell phenotype and progression in primary cutaneous lymphomas. The
      expression pattern of these three homeobox gene products (HOX-B3, HOX-B4, and HOX
      C6) was examined immunocytochemically in childhood MEDs/PNETs employing an
      indirect alkaline phosphatase conjugated technique on formalin-fixed, paraffin
      embedded tissue sections. Strong staining intensity (A, B) of HOX-B3 and HOX-B4
      was registered in all MEDs/PNETs, with immunoreactivity in between 50% and 90%
      (+3), but usually over 90% (+4) of the tumor cells. HOX-C6 was detected at medium
      intensity (mostly B) in 50% to 90% (+3) of the MED/PNET cells. This report is the
      first to describe the expression of these three homeobox gene products in
      MEDs/PNETs, and provides further evidence for the role of these proteins in the
      progression of human malignancies. The value of these genes and proteins in the
      early diagnosis and possible treatment of various human neoplasms, including
      childhood brain tumors, should be assessed in further immunocytochemical and
      molecular biological experiments.

PMID- 10928107
TI  - Proliferative activity in the progression of pigmented skin lesions, diagnostic
      and prognostic significance.
AB  - Proliferative compartments of a tumour can be determined cytophotometrically, by
      in situ hybridisation or by immunohistochemical detection of Ki67 antigen. The
      main objective of this study was to analyse the proliferative activity during the
      progression of pigmented skin lesions with respect to differential diagnostic and
      prognostic applications. The material investigated consisted of 209 pigmented
      skin lesions (31 naevi, 30 dysplastic naevi, 106 primary melanomas, 20 lymphatic
      and 22 organ melanoma metastases). Comparison of the ratios of cells in the S
      phase gained by two different methods (cytometry, in situ hybridisation) did not
      show any significant differences. The correlations between Ki67 and S-phase
      indices in every diagnostic group were highly significant. The results of forward
      and backward Cox regression were identical and only Ki67 showed an independent
      prognostic influence (p < 0.001, coefficient in regression 0.02) with change in
      risk 2% and confidence limit ranging between 1.1% and 2.9%.

PMID- 10928108
TI  - Prognostic value of the cyclin-dependent kinase inhibitor p27Kip1 in gastric
      cancer.
AB  - In the present study, the expression and prognostic role of p27 were
      immunohistochemically investigated in 413 curatively resected gastric carcinomas.
      Strong p27 expression in more than 50% of the tumour cells could be detected in
      57.4% (n = 237) whereas 42.6% of the tumours (n = 176) only showed p27 expression
      in less than 50% of the tumour cells. No significant correlation could be
      observed between p27 expression and the prognostic parameters pT category, pN
      category, blood and lymphatic vessel invasion as well as with tumour histology.
      Concerning other cell cycle associated proteins, p27 expression was inversely
      correlated with p21 expression, however, there was no correlation either with
      cyclin D1 and cyclin E or with expression of p53, bcl-2 and tumour cell
      proliferation. Univariate survival analysis revealed a poorer prognostic outcome
      for patients with tumours expressing p27 in more than 50% of the tumour cells (p
      < 0.049). However, by multivariate analysis, this prognostic influence of p27
      could not be verified as independent from the known prognostic parameters of the
      pTNM-system (p < 0.325). The present data on 413 curatively resected gastric
      carcinomas suggest, that expression of p27, analyzed alone or in combination with
      multiple cell cycle regulatory proteins, has no prognostic value in gastric
      cancer.

PMID- 10928109
TI  - Retargeting of a T cell line by anti MAGE-3/HLA-A2 alpha beta TCR gene transfer.
AB  - BACKGROUND: The T cell receptor (TCR) is an heterodimeric protein on the cell
      membrane of cytotoxic T cells (CTLs). In CTLs TCRs mediate the recognition of
      target cells through interaction with specific, MHC class I presented peptides.
      MATERIALS AND METHODS: As a model system to show proof of principle we chose the
      Jurkat/MA cell line and the HLA-A2.1 binding MAGE-3 derived peptide 271-279, as
      target specificity. RESULTS: We show that this cell line can be successfully
      transduced with the dicistronic retroviral vector (LZRS) containing cDNAs
      encoding for the complete alpha and beta chains of the selected TCR. Following
      retroviral transduction, Jurkat/MA cells do express the anti-MAGE-3 TCR on their
      membrane. The transduced TCR is functional as travoductants are successfully
      triggered, upon stimulation with T2 cells or MAGE-3+ melanoma cells loaded with
      the MAGE-3 peptide. CONCLUSION: We conclude that TCR gene transfer is possible
      and it represents a powerful therapeutic tool for the genetical modification of T
      calls of patients sullering from cancer.

PMID- 10928110
TI  - P53 expression in patients with malignant and benign breast diseases.
AB  - Immunohistochemical expression of p53 protein was studied in FNA specimens of 20
      breast ductal carcinomas, 20 fibroadenomas and 20 atypical ductal hyperplasia of
      the breast. Nine cases of breast carcinomas (45%), five fibroadenomas (25%) and
      four atypical ductal hyperplasia (20%) were found to be p53-immuno-positive. A
      statistically significant difference was found among p53 staining index of breast
      carcinomas (mean 72.55%), fibroadenomas (mean 41.2%) and atypical ductal
      hyperplasia (mean 34%). Variations in p53 expression among individual breast
      carcinomas was found, and these variations may correlate with prognosis.

PMID- 10928111
TI  - Cell growth kinetics of the human cell line Colo-205 irradiated with photons and
      astatine-211 alpha-particles.
AB  - Cell growth kinetics following Astatine-211 (211At, alpha-particle emitter) and
      photon irradiation were studied for the human colorectal cell line Colo-205. A
      growth assay using 96-well plates was chosen. The growth kinetics could be
      simulated by assuming certain fractions of cells with various proliferative
      capacities, i.e. from none up to 5 cell doublings, in addition to the defined
      survivors with remaining unlimited clonogenic capacity. No significant difference
      in cell growth characteristics was seen between 211At and photon irradiation. The
      cell doubling time, as calculated from the increment in optical density, was
      compared with the results from BrdU experiments in the early phases of growth
      (Tpot = 18.5 +/- 0.6 h for LDR (low dose rate) photon irradiated and 20.3 +/- 0.8
      hours for sham-irradiated cells 40-45 hours post-irradiation) confirming the
      transient accelerated growth of irradiated cells. No statistically significant
      difference in growth was found between LDR, MDR (medium dose rate) and HDR (high
      dose rate) photon irradiation.

PMID- 10928112
TI  - Soluble levels of CD-95, CD 95-L and various cytokines after exposing human
      leukocytes to ionizing radiation.
AB  - BACKGROUND: Local radiotherapy induces systemic effects and influences the immune
      system. Some of these effects can hardly be explained by direct cellular
      reactions, but might be triggered by humoral factors. MATERIALS AND METHODS: In
      seminoma patients we measured the influence of radiotherapy on various lymphocyte
      subsets by FACS-analysis. We analysed the release of cytokines, CD95 (Apo-1/Fas)
      and CD 95-L (Fas-Ligand) of human blood cells after exposure to ionizing
      radiation in vitro and in vivo by ELISA-technique. RESULTS: Although radiation
      leads to a differential and sustained reduction of all lymphocytes subsets in
      vivo no increase of cytokine levels, or of levels of CD95 or CD 95-L could be
      detected by ELISA in vivo or in vitro. On the contrary mitogen-induced cytokine
      production in vitro was inhibited by radiation. CONCLUSIONS: Local radiation
      induced a significant systemic decrease of all lymphocyte subsets, but neither a
      systemic release of cell death mediators like CD95 or various cytokines, nor a
      release in the extracellular space in vitro were detectable.

PMID- 10928113
TI  - Hyperthermia enhanced chemosensitivity of human malignant glioma cells.
AB  - In an effort to overcome chemoresistance of human malignant glioma cells, the
      modulation of drug-induced cell death by hyperthermia was assessed in 4 human
      malignant glioma cells lines, LN-18, LN-229, T98G and U87MG. Compared to
      normothermic conditions, pulsed 24 h drug exposure enhanced the sensitivity of
      glioma cells most strikingly with teniposide, treosulfan, topotecan and
      cisplatin, moderately with vincristine, CCNU and doxorubicin, but not with
      gemcitabine. Susceptibility to hyperthermia-mediated drug sensitization, varied
      significantly with T98G and LN-229 being strongly sensitized and U87MG being most
      resistant to the effects of hyperthermia. Hyperthermia did not significantly
      modulate drug-induced changes in cell cycle distribution. The degree of
      sensitization was independent of p53 status and of multidrug resistance (mdr)
      activity. Hyperthermia may thus be a useful approach to overcome, chemoresistance
      of human malignant glioma cells.

PMID- 10928114
TI  - Oncoselective transduction of CD80 and CD86 in tumor cell lines using an
      autonomous recombinant parvovirus.
AB  - BACKGROUND: The aim of this study was to enhance selectively the
      immunostimulatory properties of tumor cells. Based on their oncotropic
      properties, we used autonomous recombinant parvoviruses to transduce the genes
      coding for the constimulatory molecules CD80 (B7-1) or CD86 (B7-2) specifically
      into tumor cells without transducing normal cells. MATERIALS AND METHODS: After
      infection of tumor cells by these viruses, surface expression of CD80 and CD86
      molecules was assessed by FACS and enhancement of immunostimulatory properties
      was assessed in alloreactions with G-10 purified T cells. RESULTS: Infection of
      normal and transformed cells with recombinant MVM- B7-1 or B7-2 viruses leads to
      expression of costimulatory molecules only by tumor cells and confers on them the
      capacity to sensitize naive T cells in vitro. CONCLUSION: This approach should
      ultimately lead to selective expression of costimulatory molecules in tumor
      tissues in vivo without affecting normal cells.

PMID- 10928115
TI  - Cell cycle arrest and clonogenic tumor cell kill by divergent chemotherapeutic
      drugs.
AB  - BACKGROUND: Regulators of cell cycle phase transitions could be important targets
      for cancer treatment using cytostatic chemotherapy. Therefore, the extent of cell
      cycle arrest induced by different cytostatic agents has to be correlated with
      ultimate clonogenic tumor cell death. Especially the value of early cell cycle
      perturbations as indicators for the clinical efficacy of drugs should be a matter
      of investigation. METHODS: In vitro PC-3 human prostate carcinoma cells were
      incubated for 24 hours with a panel of six different chemotherapeutic drugs in
      various concentrations (Aplidine, Cisplatin, Isohomohalichondrin B (IHB), Taxol,
      Vincristine and Vinorelbine). The short term effects on the cell cycle
      distribution were determined by DNA flowcytometry while the clonogenic capacity
      of these cells was quantitated to measure the cytotoxic treatment efficacy.
      RESULTS: Significant decreases of clonogenic survival proved to be strongly
      correlated with cell cycle perturbations. IHB, Taxol, Vincristine and Vinorelbine
      resulted in accumulation (up to 87-92%) in the G2M phase, while Cisplatin and
      Aplidine led to increases in the S-phase fraction and in both G2M- as well as S
      phase fractions, respectively. CONCLUSION: Cell cycle phase perturbations appear
      to be suitable, early markers for cytotoxic drug efficacy.

PMID- 10928116
TI  - Effect of E-2-(4'-methoxybenzylidene)-1-benzosuberone on the 7,12
      dimethylbenz[alpha]anthracene-induced onco/suppressor gene action in vivo II: A
      48-hour experiment.
AB  - The cyclic chalcone analogue, E-2-(4'-methoxybenzylidene)-1-benzosuberone (MBB),
      has been found to show outstanding in vitro cytotoxic activity against P388,
      L1210, Molt 4/C8 and CEM cells, as well as against a panel of human cell lines.
      In order to determine whether this promising antineoplastic activity would extend
      to anticarcinogenic properties, the effect of MBB on the 7,12-dimethylbenz
      [alpha]anthracene (DMBA)-induced expression of the c-myc, Ha-ras and p53 genes in
      isolated RNA from the liver, lung, kidney, spleen, thymus, lymph nodes and bone
      marrow of CBA/Ca inbred mice was investigated. Earlier we had found that
      administration of MBB can reduce the DMBA-induced 24-hour gene expressions most
      effectively when it is administered prior to, or simultaneously with, the DMBA
      treatment to female CBA/Ca inbred mice. As a continuation of this study, we
      investigated the effect of MBB on the DMBA-induced gene expressions according to
      the two protocols in a 48-hour experiment. The 48-hour experiment with female and
      male CBA/Ca inbred mice also determined the compound which effectively reduced
      the DMBA-induced c-myc and Ha-ras overexpressions in almost all tissues. While
      the DMBA-induced gene expressions showed very different patterns, the
      effectiveness of the two different administrations of MBB was found to be very
      similar in the two sex groups. At the same time, contrary to the 24-hour
      experiment, increased p53 gene expression levels could be seen in several tissues
      in both sex groups. In order to get a better understanding of the effects of MBB
      on the DMBA-induced gene expressions "long-term" and "follow-up" studies should
      be performed.

PMID- 10928117
TI  - Antiestrogens affect both pathways of killer cell-mediated oncolysis.
AB  - BACKGROUND: Our previous studies indicate that antiestrogenic drugs tamoxifen
      (TX) and toremifene (TO) augment immune oncolysis induced by various killer
      cells. The underlying mechanism(s), however, have not been fully elucidated.
      MATERIALS AND METHODS: Ovarian carcinoma cells freshly isolated from cancer
      patients and the human erythroleukemia cell line, K562 were used as targets for
      killer cells and/or the anti-Fas monoclonal antibody, CH-11 in 51Cr release
      assays. In a number of experiments, extracellular Ca++ was chelated by EGTA/MgCl2
      to distinguish Ca(++)-dependent perforin/granzyme pathway from Fas/FasL pathway.
      Fas expression was studied by flow cytometry. RESULTS: Ovarian carcinoma cells
      were sensitized by antiestrogens towards enhanced cytolysis mediated by
      autologous cytotoxic lymphocytes. Antiestrogens also significantly augmented the
      killing of ovarian carcinoma cells triggered by anti-Fas monoclonal antibody.
      Flow cytometry analyses showed an upregulation of Fas (CD 95/Apo-1) upon TX or TO
      treatment in a number of cases. By contrast, antiestrogen treatment did not
      induce Fas expression in the Fas-negative K562 cells; yet, natural killer cell
      mediated cytotoxicity against K562 was augmented by antiestrogens and maximal
      lysis was achieved when both target and effector cells were treated. The presence
      of Ca++ chelator (EGTA/MgCl2) in the assay abrogated killing of K562 and its
      antiestrogen--mediated augmentation. This indicates the involvement of the
      perforin/granzyme pathway. CONCLUSION: Antiestrogens can influence both Fas/FasL
      and perforin/granzyme pathways of killer cell--mediated oncolysis.

PMID- 10928118
TI  - Effects of triterpenes from the stem bark of Dysoxylum cauliflorum on a non-small
      cell bronchopulmonary carcinoma cell line (NSCLC-N6).
AB  - Six triterpenoids and one sesquiterpene were isolated from the ethanolic extract
      of the stem bark of Dysoxylum cauliflorum. Their structures were determined from
      1D and 2D NMR and mass spectral data. Only compound 1 was cytostatic. Kinetic
      studies with ethyl eichlerianoate 1 demonstrated that this growth arrest was
      irreversible and cytofluorimetric analysis with compound 1 showed a complete
      block of NSCLC-N6 cells in the G1 phase. These events were related to a terminal
      maturation induction.

PMID- 10928119
TI  - Comparison of the DNA content in liver cell adenoma, hepatocellular carcinoma and
      regenerative nodules.
AB  - With regard to neoplasms of hepatocytes, diagnostic pitfalls have been reported
      for differentiation of liver cell adenoma (LCA) from well differentiated
      hepatocellular carcinoma (HCC). Since cytophotometric analysis of the DNA content
      with the help of image analysis has proven to be of diagnostic value in various
      neoplasms, we examined its ability to discriminate between LCA and HCC as well as
      regenerative liver nodules. The material investigated consisted of 54 cases of
      HCC, 10 benign liver tumours and 10 cases suspicious for HCC. All the benign
      liver tumours demonstrated an euploid histogram. 9 out of 10 borderline tumours
      were euploid while 1 out of 10 was suspiciously aneuploid. Among HCC, 21 out of
      54 were euploid, 18 out of 54 suspiciously and 15 out of 54 clearly aneuploid. 5c
      exceeding rate differed significantly between benign liver changes and borderline
      lesions (p = 0.0474) as well as between borderline lesions and malignant tumours
      (p = 0.0108). We conclude that the use of image cytometry is helpful as an
      additional criterion for more diagnostic accuracy in morphologically difficult
      cases.

PMID- 10928120
TI  - Short-term systemic effects of head and neck irradiation.
AB  - BACKGROUND: Various localized side effects which accompany head and neck
      irradiation [IR] have been widely reported. However, systemic side effects/have
      been only sparsely reported in the short-term period post-IR in an animal model.
      The potential modulatory role of zinc-desferrioxamine [Zn-DFO] on IR effects was
      examined because of its known ability to protect against the damage induced by
      free radicals which are mediated by redox-active metal ions. MATERIALS AND
      METHODS: We used three groups of male Wistar rats: a] sham irradiated controls b]
      irradiated [15 Gy]; c] irradiated and treated with Zn-DFO [20 mg/k] one hour
      prior to IR. During the first two weeks post-IR, body weight and food and water
      intake were monitored daily, while lymphocytes, segmented neutrophils and white
      blood cells [WBC] were counted at 10 minutes 4 and 16 hours and 1, 3, 7 and 14
      days. Serum TNF-a and IL-6 were obtained at 10 minutes and 7 days. RESULTS: On
      day 7 post-IR, body weight and food and water intake were reduced by 84% 96% and
      85% [p < 0.01], respectively in the above mentioned three groups of rats. This
      resulted in the death of 22% of the animals and was followed by recovery towards
      the end of the second week. At all time points examined between 10 minutes and 14
      days, WBC were reduced by 52-74%. On the 7th day, Zn-DFO demonstrated a 33%
      protective effect against the WBC reduction. At 10 mins post-IR, a 84.8-fold [p <
      0.01] increase of TNF-alpha, but not IL-6, was noted. However, on the 7th day
      post-IR, both TNF-alpha and IL-6 levels were increased by 48.5-fold and 102.5
      fold [0.01], respectively. CONCLUSION: The data presented delineate the severe
      short-term systemic effects of head and neck IR in a rat model. We suggest
      considering the severe cachectic and immunocompromised status of the animals when
      performing various short-term studies with this model. During this period
      nutritional and immunological support for the examined animals is recommended.
      Further evaluation of the underlying mechanisms of IR-induced leukopenia and
      cachexia in animals and the possible implications for humans is warranted.

PMID- 10928121
TI  - The role of the reticulo-epithelial (RE) cell network in the immuno
      neuroendocrine regulation of intrathymic lymphopoiesis.
AB  - The thyrnus provides an optimal cellular and humoral microenvironment for the
      development of immunocompetent T lymphocytes. Although yolk sac derived pre-T,
      committed hematopoietic stem cells enter the thymus using a homing receptor, the
      immigration process also requires secretion of a peptide, called thymotaxin by
      the cells of the reticulo-epithelial (RE) network of the thymic cellular
      microenvironment. The thymic RE cells are functionally specialized based on their
      location within the thymic microenvironment. Thus, although subcapsular,
      cortical, and medullary RE cells are derived from a common, endodermal in origin
      epithelial precursor cell, their unique location within the gland causes their
      specialization in terms of their immunophenotypical and in situ physiological
      properties. The subcapsular, endocrine, RE cell layer (giant or nurse cells) is
      comprised of cells filled with PAS positive granules, which also express A2B5/TE4
      cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to the
      medullary RE cells, these subcapsular nurse cells also produce thymosins beta 3
      and beta 4. The thymic nurse cells (TNCs) display a neuroendocrine cell specific
      immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+,
      UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells
      display MHC Class II (HLA-DP, HLA-DQ, HLA- DR) molecule restriction. These cells
      also contain transforming growth factor (TGF)-beta type II receptors and are
      involved in the positive selection of T cells. Transmission electronmicroscopic
      (TEM) observations have defined four, functional subtypes of medullary RE cells:
      undifferentiated squamous, villous and cystic. All subtypes were connected with
      desmosomes. The secreted thy nic hormones, thymulin, thymosin-alpha 1 and
      thymopoietin (its short form, thymopentin or TP5) were detected
      immunocytochemically to be produced by RE cells. Thymic RE cells also produce
      numerous cytokines including IL-1, IL-6, G-CSF, M-CSF, and GM-CSF molecules that
      likely are important in various stages of thymocyte activation and
      differentiation. The co-existence of pituitary hormone and neuropeptide secretion
      [growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH),
      thyroid stimulating hormone (TSH), triiodothyronine (T3), somatostatin, oxytocin
      (OT), follicle stimulating hormone (FSH), luteinizing hormone (LH), arginine
      vasopressin (AVP), growth hormone releasing hormone (GHRH), corticotropin
      releasing hormone (CRH), nerve growth factor (NGF), vasoactive intestinal peptide
      (VIP), pro-enkephalin (pro-enk), and beta-endorphin (beta-end)], as well as
      production of a number of interleukins and growth factors and expression of
      receptors for all, by RE cells is an unique molecular biological phenomenon. The
      thymic RE cell network is most probably comprised of cells organized into sub
      networks--functional units composed of RE cells with differing hormone
      production/hormone receptor expression profiles, involved in the various stages
      of T lymphocyte maturation. Furthermore, it is quite possible that even on the
      level of individual RE cells, the numerous projections associated with a single
      cell, which engulf developing lymphocytes, nurturing and guiding them in their
      maturation, may differ in their hormone production and/or hormone receptor
      expression profile, thus allowing a single cell to be involved in distinct,
      separate steps of the T cell maturation process. Based on our systematic
      observations of the thymus in humans and other mammalian species, we suggest that
      the thymic RE cells represent an extremely important cellular and humoral network
      within the thymic microenvironment and are involved in the homeopathic regulation
      mechanisms of the multicellular organism, in addition to the presentation of
      various antigens to developing lymphocytes, and providing growth regulatory
      signals which may range from stimulatory to apoptotic signaling within the
      thymus. (ABSTRACT TRUNCA

PMID- 10928122
TI  - Combined radioimmunotherapy and radiotherapy of liver metastases from colorectal
      cancer: a feasibility study.
AB  - BACKGROUND: A combination of radioimmunotherapy (RIT) and radiotherapy (RT)
      should allow one to increase the dose of radiation targeting a particular tumour
      without the concomitant increase of toxic side effects. This might be obtained if
      the dose limiting side effect of each individual radiation therapy concerned
      different organs. METHODS: Six patients with limited liver metastatic disease
      from colorectal cancer were treated with 6.9 GBq (range 4.7 to 8.4 GBq) 131I
      labelled anti-CEA MAb F(ab')2 fragments combined with 20 Gy RT to the liver. Both
      treatments were given in close association, according to timing schedules
      evaluated in animals that gave the best results. RESULTS: Reversible bone marrow
      and liver toxicity was observed in 6 and 5 patients, respectively. Three patients
      who first received 20 Gy RT to the liver, showed a significant platelet drop upon
      completion of RT. Repeat computerized tomography (CT) after 2 months showed a
      minor response in 1 patient and stable disease in 3 patients. CONCLUSION: The
      study shows potential ways of combining RIT and RT, suggesting that this
      combination is feasible for the treatment of liver metastases.

PMID- 10928123
TI  - Absence of mutations in the NBS1 gene in B-cell malignant lymphoma patients.
AB  - BACKGROUND: Nijmegen breakage syndrome (NBS), also known as ataxia-telangiectasia
      (AT) variant, is an autosomal recessive disorder characterized by microcephaly,
      growth retardation, severe combined immunodeficiency and a high incidence of
      lymphoid carcinoma, the majority of which are B-cell lymphomas. To determine
      whether the NBS1 gene is a tumor suppressor gene in B-cell lymphoma, we screened
      B-cell malignant lymphoma (ML) for any evidence of NBS1 mutation. MATERIALS AND
      METHODS: Sequence analysis of the NBS1 gene was performed from PCR products
      amplified from the DNA of 12 extracranial ML or RT-PCR products amplified from
      cDNA of 8 primary central nervous system lymphoma. RESULTS: Direct sequence
      analysis revealed that no NBS1 mutations were present in any of these patients.
      CONCLUSION: The present results suggested that the contribution of NBS1 mutations
      to B-cell ML was minimal, despite the fact that the NBS1 gene was causative
      factor in these cases.

PMID- 10928124
TI  - Accelerated decline of blood glucose after intravenous glucose injection in a
      patient with Cowden disease having a heterozygous germline mutation of the
      PTEN/MMAC1 gene.
AB  - The PTEN/MMAC1, a putative tumor suppressor, has been demonstrated to
      dephosphorylate phosphatidylinositol 3, 4, 5-triphosphate, a key molecule
      involved in the insulin signaling pathway. The PTEN may act, therefore, as a
      negative regulator of insulin signaling. The patient with Cowden disease, having
      a heterozygous PTEN/MMAC1 gene mutation, a C to T substitution of a single base
      at codon 130, was suspected to have decreased amount of PTEN protein with
      phosphatase signature motif. We thought that the patient might be more sensitive
      to insulin than normal subjects. As expected, administration of a bolus of
      glucose resulted in a more rapid clearance of blood glucose than was observed in
      5 control subjects, indicating the presence of insulin hypersensitivity in the
      patient. The euglycemic hyperinsulinemic clamp study provided additional
      evidence.

PMID- 10928125
TI  - Genetic alterations in human prostate cancer: a review of current literature.
AB  - We review the literature dealing with genetic alterations in human prostate
      cancer. We also discuss genetic predisposition and the roles of various proto
      oncogenes and tumor-suppressor genes in prostate cancer initiation, progression,
      and metastasis. The role of telomere dynamics in prostate cancer metastasis and
      the induction of apoptosis is also briefly discussed.

PMID- 10928127
TI  - A case of pulmonary adenocarcinoma with overexpression of multidrug resistance
      associated protein and p53 aberration.
AB  - A 66-year-old female patient underwent left upper lobectomy and dissection of the
      mediastinal lymph nodes. The pathological diagnosis was well-differentiated
      papillary adenocarcinoma of the lung with metastasis to the mediastinal lymph
      nodes, p-T2N2MO, stage IIIA. After the operation, she was treated by chemotherapy
      including lipophilic anticancer compounds (carboplatin and VP-16). The patient
      unexpectedly showed long survival for 6 years and 2 months without obvious
      recurrence or metastasis of the cancer. The anticancer compounds were not
      effective on the recurrent lesions and then she died due to respiratory failure 8
      months after recurrence. The autopsy revealed pleural dissemination and
      intrapulmonary metastasis. Immunohistochemical analysis showed increased
      multidrug resistance-associated protein (MRP)-positive tumor cells in the
      recurrent and metastatic lesions, while few MRP-positive cells were apparent in
      the primary lesion. The MRP-positive cells were accompanied by p53 nuclear
      accumulation in the carcinoma. This was a case of pulmonary adenocarcinoma with
      acquired multidrug resistance caused by MRP overexpression and aberrant p53 after
      chemotherapy.

PMID- 10928126
TI  - New drugs in recurrent high grade gliomas.
AB  - BACKGROUND: The incidence of Central Nervous System (CNS) neoplasias ranges from
      3.8 to 5.1 cases per 100,000 inhabitants. In the presence of recurrence, the
      treatment is problematic; chemotherapy is experimental, primarily because the
      response is palliative and of limited duration. MATERIALS AND METHODS: This
      article analyzes the new drugs that have been introduced for the treatment of
      these patients in recent years, the objective response, the TTP and the MST.
      RESULTS: The most encouraging results to date come from studies of temozolomide,
      which is one of the most active and best tolerated drugs in recent years.
      CONCLUSION: New approaches to chemotherapy treatment are necessary. Enrollment of
      patients into rigorous, well-conducted, clinical trials, both at tumor diagnosis
      and after tumor recurrence, will generate new information regarding
      investigational therapies and may offer improved therapies for patients with
      malignant gliomas.

PMID- 10928129
TI  - Expression of p53 and p21 is useful for the prediction of preoperative
      chemotherapeutic effects in esophageal carcinoma.
AB  - The p53 and p21 genes are associated with G1 arrest during the cell cycle and
      with apoptosis, both of which have a close relationship with the effect of
      chemotherapy. In this study, we investigated the correlation between p53 and p21
      expression in biopsy specimens and the histological effect of chemotherapy in
      esophageal carcinoma. A total of 30 patients with esophageal squamous cell
      carcinoma received preoperative chemotherapy, then underwent esophagectomy with
      lymph node dissection. The response rate of primary lesion and metastatic nodes
      was 20.0% and 25.9%, respectively. The positive rate of p53 and p21 expression
      was 56.7% and 36.7%, respectively. Preoperative chemotherapy against primary
      lesions was ineffective in all the patients who expressed p53, but not p21. In
      contrast, chemotherapy was effective against metastatic lymph nodes which were
      p53 negative but p21 positive. These findings suggest that p21 positive
      expression in the absence of p53 is associated with favorable effects of
      preoperative chemotherapy in patients with esophageal carcinoma. Therefore, the
      expression of these genes should be examined in biopsy specimens to predict the
      chemotherapeutic outcomes in patients with esophageal carcinoma.

PMID- 10928128
TI  - Reduced expression of ICE/caspase1 and CPP32/caspase3 in human hepatocellular
      carcinoma.
AB  - The interleukin-1(-converting enzymes (ICE)/caspase1 and the CPP32/caspase3,
      cysteine proteases, play an important role in the maintenance of homeostasis by
      inducing apoptosis. Since human hepatocellular carcinomas (HCCs) demonstrate
      strong resistance to apoptosis, we investigated the expression of ICE and CPP32
      in human HCCs. Reverse transcription PCR analysis revealed that one out of five
      HCC tissues showed no band of ICE mRNA and two out of five HCC tissues showed no
      band of CPP32 mRNA. An immunohistochemical study of 20 cases of HCC tissues and
      non-tumor parts revealed that immunoreactivity of ICE and CPP32 was
      preferentially observed in the cytoplasm, appearing as a diffuse and homogeneous
      pattern. Some nuclei also stained with anti-ICE antibody or anti-CPP32 antibody
      and demonstrated apoptotic features. Overall, the expression of ICE and CPP32
      were significantly down-regulated in the HCCs compared to nontumor cells. In situ
      nick end labeling method (TUNEL) labeling index significantly decreased according
      to the decreasing staining intensity of CPP32. However, there was no tendency for
      the TUNEL labeling index to decrease with decreasing ICE staining intensity. Our
      results suggested that the expression of ICE and CPP32 were down-regulated and
      that especially reduced expression of CPP32 may contribute to resistance against
      apoptosis in human HCCs.

PMID- 10928130
TI  - Renal cell carcinoma metastatic to the skin.
AB  - BACKGROUND: Cutaneous metastases from renal cell carcinoma are rarely diagnosed
      during life. We reviewed the cases of our institute and from the Japanese
      literature and analyzed them to define the clinical features. PATIENTS AND
      METHODS: Six patients with cutaneous metastases from renal cell carcinoma were
      treated in our institute. Clinical data and follow-up information of these
      patients were reviewed. RESULTS: The skin metastatic lesions were found before
      the renal lesion was discovered in one case and they were found after the
      diagnosis had been established in 5. Four patients presented with solitary
      cutaneous metastasis at the time of diagnosis of the skin metastatic lesion. Five
      patients had other sites of metastases such as the lung, liver and bone at the
      time of diagnosis of cutaneous metastases. Five patients died of renal cell
      carcinoma at mean 23.8 months after presenting with cutaneous metastases.
      CONCLUSION: Our 6 cases bring the total reported in the Japanese literature to 75
      cases. The results of these 75 cases revealed that the duration from the time of
      diagnosis of renal cell carcinoma to detection of the cutaneous metastasis was
      relatively long but the prognosis of patients with these metastatic skin lesions
      was poor. Cutaneous metastases from renal cell carcinoma were regarded as a late
      manifestation of the disease.

PMID- 10928131
TI  - Noninvasive measurement of the electrical bioimpedance of breast tumors.
AB  - The purpose of this study was to evaluate the possibility of differential
      diagnosis of tumors, such as breast cancer, by measuring the mammary electrical
      bioimpedance via the skin surface noninvasively and by examining the relationship
      between the tissue structure of the breast and electrical bioimpedance. The
      mammary electrical bioimpedance was measured in 24 patients with breast cancer.
      Taking into account the measurement results and the distribution of the mammary
      glands and fatty tissue, a breast model with tumors was proposed. Based on this
      model, the distributions of the electric potential and electric field in the
      tissue were theoretically analyzed by the three-dimensional finite element
      method. In clinical cases, the Re values of the diseased breast were
      significantly larger than those of the contralateral healthy breast. In
      theoretical analysis based on the breast model, the Re value of mammary
      electrical bioimpedance varied due to the structure of the breast, that is, the
      ratio of fatty tissue to mammary gland and the presence of mammary tumors. The
      results of the measurement agreed with the theoretical analyses. These results
      suggest that differential diagnosis of breast tumors is possible by measuring the
      mammary electrical bioimpedance using noninvasive electrodes on the skin.

PMID- 10928132
TI  - Immunohistochemical characterization of p57KIP2 expression in human esophageal
      squamous cell carcinoma.
AB  - Functional defects in the CIP/KIP family of cyclin-dependent kinase inhibitors
      (CDKIs) have been shown to be associated with human malignancies. We
      immunohistochemically examined p57KIP2 (p57) expression in 92 patients with human
      esophageal squamous cell carcinoma (SCC) to determine the relationship between
      this expression and those of cyclin D1 and E. The p57 labeling index (LI)
      (defined as the percentage of p57-positive cells) in esophageal SCC was 43.3 +/-
      3.2% (mean +/- standard error of the mean). In non-neoplastic esophageal
      epithelium, p57 staining was more frequently observed in the basal and parabasal
      cells than in surface layer cells. Immunostaining for cyclin D1 and E was
      observed in 28.2% (28/92) and 32.6% (30/92) of tumors, respectively. The median
      p57 LI in cyclin D1-positive cases was 66.2, and significantly higher than that
      in negative cases (31.9%) (p = 0.0009). There was no significant relationship
      between p57 LI and cyclin E expression (p = 0.147). As determined using Kaplan
      Meier's method, loss of p57 immunoreactivity was not a prognostic factor for
      esophageal SCC (p = 0.548). Our in vivo findings suggested that p57 protein
      expression was positively correlated with cyclin D1 expression and that loss of
      p57 protein expression alone does not affect progression of esophageal SCC.

PMID- 10928133
TI  - Epstein-Barr virus strain characterisation in South African patients with
      nasopharyngeal carcinomas.
AB  - Epstein-Barr virus (EBV) has been implicated in various diseases, among others,
      nasopharyngeal carcinoma (NPC). In this study we investigated the frequency and
      subtype distribution of EBV in 39 NPCs. The presence of EBV was detected by using
      a nested PCR to amplify the Bam Hl W-fragment of the genome. Two regions were
      targeted for subtype analysis, namely the EBNA-2A and EBER regions. PCR was used
      to amplify these regions, and the EBER region was sequenced to detect subtype
      specificity. The results showed that EBV could be detected in 82% (31/38) of the
      tumours. In 15 of these, EBNA subtypes could be identified of which 14 were
      subtype A and one tumour had both subtypes A and B present. The EBER region was
      amplified in 21 samples. The majority of cases (18/21) demonstrated a mutation
      profile which consisted of 5 type B and one type A mutations. The consensus type
      is therefore type B. IN CONCLUSION: a strong association was found between EBV
      and NPCs in our group of patients and their "consensus" genotype was A/B based on
      the two genome areas investigated.

PMID- 10928134
TI  - Surgical cytoreduction during second-look laparotomy in patients with advanced
      ovarian cancer.
AB  - BACKGROUND: The impact of surgical cytoreduction performed during second-look on
      the survival of patients with advanced ovarian cancer is still under debate.
      MATERIALS AND METHODS: The present retrospective investigation assessed 81
      patients with advanced ovarian cancer who underwent second-look laparotomy after
      initial cytoreductive surgery and six cycles of platinum-based chemotherapy.
      RESULTS: At the beginning of the second-look, 31 patients were in pathological
      complete response, 7 had microscopic residual disease, 22 had macroscopic
      residual disease < 2 cm and 21 had a larger residuum. Twenty-two (51.2%) of the
      43 patients with macroscopic disease underwent surgical cytoreduction during the
      second-look: 11 patients were completely cytoreduced, whereas 11 were debulked
      from residuum > 2 cm to macroscopic residuum < 2 cm. Patients with microscopic
      residual disease after the second-look had improved survival when compared to
      those with macroscopic residuum after re-exploration (median survival, 43 months
      versus 19.5 months, p = 0.002). Among the former, no difference in survival was
      detected between the patients who had microscopic disease at the beginning of the
      second-look and those who were surgically cytoreduced to microscopic disease.
      Moreover, the patients with macroscopic residuum < 2 cm after the second-look had
      a better survival than those with a larger residuum after re-exploration (median
      survival, 24 months versus 10 months, p = 0.0001). Among the former, no
      difference in survival was seen between the patients who had residual disease < 2
      cm at the beginning of the second-look and those who were surgically cytoreduced
      to < 2 cm. However, ovarian cancer recurred in all the patients with small or
      large macroscopic residuum after the second-look. CONCLUSION: The complete
      resection of macroscopic persistent tumor seems to give ovarian cancer patients
      the highest likelihood of long-term survival and should represent the goal of
      surgical cytoreduction during second-look laparotomy.

PMID- 10928135
TI  - Amplification and overexpression of HER-2/neu are uncommon in advanced stage
      melanoma.
AB  - The HER-2/neu proto-oncogene is a useful prognostic and predictive biomarker in
      breast cancer. In addition, use of a humanized monoclonal antibody against HER
      2/neu has recently been shown to have efficacy in the treatment of metastatic
      breast cancer. In order to examine the potential of HER-2/neu as a biomarker and
      as a target for HER-2/neu monoclonal antibody treatment in melanoma, we examined
      the HER-2/neu status in 40 advanced stage melanomas. Using fluorescence in situ
      hybridization for determining the gene amplification status and
      immunohistochemistry for detecting protein overexpression, we found that only one
      out of 40 cases of melanoma had an altered HER-2/neu status. These results
      demonstrated that HER-2/neu amplification and overexpression are not common in
      advanced stage melanoma and thus, HER-2/neu would have limited value as a
      biomarker or as a target for immunotherapy in melanoma.

PMID- 10928136
TI  - Improvement of the recurrence-free interval using biological adjuvant therapy in
      uveal melanoma.
AB  - This study was an attempt to compensate for an alleged aetiological deficiency in
      melanoma by the prophylactic oral administration of the essential biological
      components missing. Nine random patients suffering from high-risk uveal melanoma
      (T3) were, in this preliminary study, treated secondarily with biological dietary
      adjuvants after primary standard therapy, enucleation or brachytherapy. Secondary
      treatment consisted of certain natural amino-acids, trace-element salts, folic
      acid and a diet containing neurogenic lipid components. It entailed no side
      effects, no toxicity and was inexpensive. None of these nine patients has
      suffered recurrent disease. The mean follow-up time was over 80 months (median
      69, range 58-140 months). Local tumour control was 100%. This clinical result is
      significantly better (p = 0.018) as compared to similar T3 uveal melanoma
      patients in standard care who did not receive adjuvant dietary remedies after
      primary treatment. The control patients consisted of similar adjusted T3 cases
      selected from the Swedish official registries, and T2 patients from Germany.
      Based on the previous positive clinical results obtained with cutaneous malignant
      melanoma in bioimmunotherapy this additional positive result supports the notion
      that biological components administered orally may compensate for the etiological
      deficiency leading to malignant melanoma.

PMID- 10928137
TI  - An intensive follow-up does not change survival of patients with clinical stage I
      endometrial cancer.
AB  - BACKGROUND: The clinical benefit of an intensive follow-up protocol in
      endometrial cancer patients is still uncertain. MATERIALS AND METHODS: One
      hundred and thirty-three patients underwent initial abdominal surgery for
      clinical stage I endometrial cancer between January 1988 and December 1997 and
      were periodically followed-up until April 1999 or until death. After surgery, 89
      patients received postoperative adjuvant treatment. Periodical surveillance
      included physical examination, vaginal smear and abdominal-pelvic ultrasound
      every 3-4 months for the first 2 years from surgery, every 6 months for the next
      3 years and yearly thereafter. Chest X-ray was performed every 6 months for the
      first 2 years, every year for the next 3 years and with individually increasing
      intervals afterwards. An abdominal-pelvic CT scan was carried out yearly for 5
      years. RESULTS: Twenty-four patients (18.0%) developed recurrent disease after a
      median time of 17.5 months (range, 6-64 months). Five-year actuarial disease-free
      survival was 81.2% in the whole series, and in detail 94.2% in the subset of
      patients with FIGO stage Ia grade 1 or 2 endometrioid adenocarcinoma, or stage Ib
      grade 1 endometrioid adenocarcinoma (low-risk), compared to 76.0 (p = 0.0472) in
      the subset of patients with stage Ia grade 3 endometrioid adenocarcinoma, stage
      Ib grade 2 or 3 endometrioid adenocarcinoma, stage equal to or greater than Ic
      endometrioid adenocarcinoma any grade, and aggressive histologies (high-risk).
      The site of recurrent disease was local in 6 (25.0%) patients, distant in 17
      (70.8%), and local plus distant in 1 (4.2%). Eleven (45.8%) recurrences were
      symptomatic and 13 (54.2%) were asymptomatic. The median survival after
      recurrence was 10 months. Survival was longer in patients who relapsed after 17.5
      months from initial surgery when compared to those who relapsed earlier (p =
      0.02). Conversely, survival after recurrence was not related to patient
      characteristics at diagnosis, such as FIGO stage, tumor grade, myometrial
      invasion, histologic type, and lymph node status. It is noteworthy that survival
      was similar in asymptomatic women, in whom the relapse was occasionally detected
      by follow-up examinations, and in symptomatic ones. CONCLUSION: An intensive
      surveillance protocol seems to have no significant impact on the outcome of
      patients with clinical stage I endometrial cancer. Simplified follow-up programs
      tailored for patient subsets with different recurrence risk are required.

PMID- 10928138
TI  - Cisplatin, vindesine, mitomycin-C and 13-cis retinoic acid in the treatment of
      advanced non small cell lung cancer. A phase II pilot study.
AB  - BACKGROUND: Thirteen-cis retinoic acid (RA) has been shown to have growth
      inhibitory and differentiative activity on non-small cell lung cancer (NSCLC)
      cells in vitro. This promoted the rationale for combining RA with three active
      drugs, cisplatin (CDDP) vindesine (VDS) and mitomycin-c (MMC) in the treatment of
      advanced NSCLC. PATIENTS AND METHODS: Patients with a histologically confirmed
      non-resectable NSCLC, measurable lesion, performance status < or = 3, and
      informed consent were enrolled. The chemotherapy schedule included cisplatin 60
      mg/m2 and mitomycin-c 10 mg/m2 day 1 and vindesine 3 mg/m2 on days 1 and 5, every
      4 weeks. RA was administered orally, at a dose of 0.5 mg/kg, 5 days per week,
      during chemotherapeutic intervals and to responding patients until disease
      progression was observed. RESULTS: Thirty patients, receiving a total of 163
      chemotherapy courses, were evaluated for response and toxicity. Objective
      responses included complete response in 2 patients (7%), partial response in 10
      patients (33%), stable disease in 9 patients (30%) and progressive disease in 9
      patients (30%), (response rate 40%: Confidence interval 95% 22.7% to 59.4%).
      Median time to progression was 8.6 months (range 3.9-45+). Median overall
      survival was 11.3 months (range 1-45+). The 1-year survival rate was 47%.
      Toxicity (WHO) included nausea and vomiting grade 2 in 6 patients, transient
      ileus in 3 patients and grade 3-4 leukopenia in 5 patients. Two patients
      underwent surgical resection of residual disease and remain in CR. CONCLUSIONS:
      The addition of RA to cisplatin, vindesine and mitomycin-c is feasible and shows
      some activity in the treatment of NSCLC, with manageable toxicity.

PMID- 10928139
TI  - Colonoscopy in symptomatic patients with positive family history of colorectal
      cancer.
AB  - BACKGROUND: Most patients with colorectal cancer (CRC) develop clinical signs and
      symptoms which are not specific for CRC, and usually at a late stage of the
      disease, resulting in a considerable delay of the diagnosis. In our study we
      examined patients with bowel symptoms which were at increased risk for developing
      CRC, because of their family history. METHODS: Over the last 6 years, colonoscopy
      was performed in 203 patients with colorectal symptoms, who had at least one Ist
      degree relative with CRC, at the Colorectal Surgery Unit of St George's Hospital.
      Five hundred ninety two individuals without CRC family history and with either
      rectal bleeding (n = 479), or with change of bowel habits (n = 113) were used as
      control group. RESULTS: In the group of patients with family history of CRC 81
      colonic lesions were found in 53 patients (53/203, 26%). Patients with family
      history of CRC were grouped in three categories according to their main symptom.
      In the subgroup of patients with bleeding (n = 129) there were found 46 colonic
      lesions in 33 patients. In the subgroup of patients with change of bowel habits
      (n = 45) we were able to detect 39 colonic lesions. In the group of patients with
      abdominal pain (n = 29) 4 patients had a metaplastic polyp and one patient had a
      neoplastic polyp. With regard to the number of 1st degree relatives with CRC, we
      found that 16/172 (9%) patients with one such relative and 4/31 (13%) of the
      patients with two relatives were diagnosed with neoplastic polyps. CONCLUSIONS:
      Total colonoscopy (TC) is an excellent diagnostic procedure for the examination
      of symptomatic patients with positive family history of colorectal cancer. TC has
      a diagnostic role detecting the cause of symptoms or excluding the presence of
      malignancy. Simultaneous resection of the neoplastic and metaplastic polyps,
      provides an additional, secondary prevention of CRC.

PMID- 10928140
TI  - Mucoepidermoid carcinoma of the trachea with airway hyperresponsiveness.
AB  - We report a case of mucoepidermoid carcinoma of the trachea in a 23-year-old
      pregnant female in her 39th week. The patient had cough and wheezing in the early
      morning for 9 months before admission. No abnormalities were detected on a chest
      roentgenogram. At Caesarean section, fiberscopy revealed a polypoid lesion
      narrowing the trachea. The pathologic diagnosis made from the biopsy specimen
      obtained was low-grade mucoepidermoid carcinoma and the lesion was resected.
      Airway hyperresponsiveness was shown before resection with airflow limitation,
      however, airway reactivity and airflow limitation improved 1 year after
      resection.

PMID- 10928141
TI  - Fas-Fas ligand pathway does not actively work in extrahepatic bile duct
      carcinoma.
AB  - Fas and Fas ligand expression were immunohistochemically investigated in 34
      extrahepatic bile duct carcinomas (BDC) and nine ampulla carcinomas (AC). Fas
      expression was regarded as positive in 22 BDC cases (64.7%). The absence or
      decreased expression of Fas was frequently observed in cases with high biological
      aggressiveness such as advanced stage, moderate or poor differentiation, lymph
      node metastasis, aberrant p53 expression and high Ki-67 labeling index. A similar
      tendency was observed in AC where two cases without Fas expression were poorly
      differentiated with a high Ki-67 labeling index. Fas ligand expression in
      infiltrating mononuclear cells adjacent to the carcinoma nests was observed in
      only four BDC (11.1%) and in none of the AC examined. Fas ligand expression in
      carcinoma cells was observed in only one BDC, which showed Fas ligand expression
      also in mononuclear cells and not in any AC case. These results suggest that,
      although BDC and AC very frequently express Fas, Fas-mediated apoptosis is only
      occasionally induced in carcinoma cells because of the lack of Fas ligand
      expression in infiltrating mononuclear cells in these carcinomas.

PMID- 10928142
TI  - Presence of human beta-defensin-2 in oral squamous cell carcinoma.
AB  - The purpose of this study was to demonstrate immunohistochemically the
      localization and distribution of human beta-defensin-2 (HBD-2), a peptide with
      antimicrobial activity, in oral carcinoma tissues. Tissue samples were embedded
      in paraffin, and HBD-2 was immunostained by the streptavidin-biotin coupled
      peroxidase method. Cancer cells in the cornified region of well differentiated
      squamous cell carcinomas were stained intensely. Stained cancer cells detected by
      anti-HBD-2 antibody were scattered among the cells of the non-cornified region.

PMID- 10928143
TI  - Prognostic significance of matrix metalloproteinases 2 and 9 in bladder cancer.
AB  - BACKGROUND: The levels of matrix metalloproteinases MMP-2 and MMP-9 (type IV
      collagenases), which degrade the extracellular matrix of the basement membrane,
      were evaluated as prognostic indicators of metastasis in urothelial carcinoma.
      MATERIALS AND METHODS: Quantitative gel zymography and immunohistochemistry were
      used and compared with clinical data at the follow-up period of 36 months.
      RESULTS: Zymographical analysis of the levels of MMP-9 and active MMP-2 showed a
      statistically significant increase with tumor grade and invasiveness. This
      correlation was confirmed by immunohistochemical analysis of MMP-9 expression.
      However, the correlation between the levels of both gelatinases with recurrence
      in superficial tumours or progression in invasive tumours was not statistically
      significant. CONCLUSION: MMPs may have an important role in the invasion
      mechanism of urothelial cancer and could be useful prognostic markers for
      patients with bladder carcinoma. The relationship between MMP-2 and MMP-9
      expression and the metastatic potential of bladder carcinoma needs further
      evaluation in subsequent clinical studies.

PMID- 10928144
TI  - Long-term tamoxifen treatment: a possible aetiological factor in the development
      of uterine carcinosarcoma: two case-reports and review of the literature.
AB  - Two cases of uterine carcinosarcoma developing after long-term tamoxifen (TAM)
      treatment are presented. The patients, 67 and 72 years old, were treated with TAM
      for 6 and 7 years, continuously. They both developed an heterologous malignant
      mixed Mullerian tumor (mmMt). At laparotomy, an advanced stage of disease was
      found with peritoneal spread. In spite of the surgical and the postoperative
      treatment, they both died of disease, 3 and 10 months later. There are only 10,
      well documented, similar cases reported. Another 7 were identified in series of
      uterine malignancies developing after TAM treatment. Considerable evidence
      suggests that mmMt represents an epithelial cancer with sarcomatous
      dedifferentiation. Prolonged (> 5 years) TAM treatment may represent a causative
      factor in the development of this highly lethal disease (80% of the reported
      patients had a dismal prognosis). Large uterine polyps with special histological
      features, may represent an intermediate step in the tumor formation. Close follow
      up of the patients is warranted.

PMID- 10928145
TI  - Expression of drug resistance protein related to Tc-99m MIBI breast imaging.
AB  - Adjuvant and neoadjuvant chemotherapy is increasingly being used in the treatment
      of breast cancer patients. However, drug resistance plays an important role in
      chemotherapy failure in this cancer. The aim of this study was to determine the
      correlation between technetium-99m sestamibi (Tc-99m MIBI) breast imaging results
      and expression of the drug resistance proteins (p-glycoprotein (Pgp), Ki-67 and
      mutant p53) in human breast cancer tissues. Twenty-four breast cancer patients
      underwent Tc-99m MIBI breast imaging before surgery or biopsy. Protein expression
      was investigated by immunohistochemical studies on multiple nonconsecutive
      sections of surgery or biopsy samples. Tumor to background (T/B) ratios
      calculated by Tc-99m MIBI breast imaging were correlated with protein expression
      determined by immunohistochemical studies. The T/B ratios were significantly
      lower in 8 patients with positive Pgp expression (Group 1) when compared with 16
      patients with negative Pgp expression (Group 2) (1.40 +/- 0.11 and 2.76 +/- 0.60,
      p < 0.05). However, the differences of T/B ratios between the patients with
      positive and negative Ki-67 mutant p53 expression were not significant. Our data
      confirmed that Tc-99m MIBI breast imaging is useful for determination of the
      presence of Pgp expression in breast cancer patients. No significant relationship
      between Tc-99m MIBI breast imaging results and Ki67/mutant p53 was found.

PMID- 10928146
TI  - Antiestrogens sensitize human ovarian and lung carcinomas for lysis by autologous
      killer cells.
AB  - BACKGROUND: The antiestrogens tamoxifen (TX) and toremifene (TO) were shown
      previously to enhance the lysis of target cells by natural killer cells (NK),
      lymphokine activated killer (LAK) cells, and by cytotoxic T lymphocytes (CTL).
      MATERIALS AND METHODS: CTL were cultured from lung cancer tissue and from ascites
      fluid of ovarian carcinoma patients with the aid of human recombinant interleukin
      2 (hrIL-2). The target, effector or both cell populations were pretreated by TX,
      TO and/or with human recombinant interferon-alpha (IFN-alpha). RESULTS:
      Significant enhancement of cytotoxicity occurred when the tumor targets or both
      the target and effector cells were treated with TX, TO or when these drugs were
      used in combination with IFN-alpha. The lytic activity of CTL cultured from
      draining lymph nodes of lung cancer patients, was also observed after similar
      treatment. The lytic effect of autologous LAK cells derived from peripheral blood
      was increased to a lesser extent, which could be amplified by additional
      treatment with IFN-alpha. CONCLUSIONS: The antiestrogens TX and TO and IFN-alpha
      enhance the lysis of autologous tumor cells by CTL and LAK effectors.

PMID- 10928147
TI  - Outpatient sequential high dose alkylation with stem cell support for patients
      with advanced breast cancer: a phase I-II study.
AB  - We evaluated the feasibility of administering, in an out-patient setting, a
      sequential high dose alkylating regimen with hematopoietic growth factor (HGF)
      and stem cell support to patients with advanced breast cancer. Peripheral blood
      stem cells (PBSC) were previously collected after chemotherapy and HGF. Two
      consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days
      later, BCNU (B). Three dose levels of each agent were administered in cohorts of
      consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of
      PBSC followed both cycles. Toxicity and response were evaluated according to the
      WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in
      the first, 12 in the second and 10 in the third dose level. In all cases, B was
      administered after T with a median delay of 25 days because of grade 3/4
      hematological toxicity. 4 patients did not receive B because of previous lung
      radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19
      patients with measurable lesions were considered for response. The objective
      response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600
      mg/m2 to conduct a phase II study in metastatic breast cancer and even to
      administer B before T.

PMID- 10928148
TI  - Breast size as risk factor for tumor size at diagnosis.
AB  - BACKGROUND: A prospective study was conducted to determine whether patients with
      larger breasts show larger tumors. MATERIALS AND METHODS: 123 patients with
      primary breast cancer were evaluated (median follow-up 36 months). Breast size
      was determined as a reflection of cup size. RESULTS: Cup size correlated with
      tumor diameter at diagnosis (p = 0.0038). On average, cup sizes were larger in
      postmenopausal than in premenopausal women (p = 0.0011), however, postmenopausal
      women did not show larger tumors than premenopausal. There was a significant
      positive correlation between body mass index, body weight and breast size (p <
      0.0001). The mode of tumor detection (self vs. not self) was independent of
      breast size. No correlation was found between breast size and the patient's
      height, duration of breast feeding, smoking behavior or amount of alcohol
      consumption, hormone replacement therapy or use of oral contraceptives, number of
      involved lymph nodes or DFS and OS. CONCLUSION: Patients with larger breasts
      showed larger tumors. The mode of tumor detection is independent of breast size.

PMID- 10928149
TI  - Docetaxel and autonomic cardiovascular control in anthracycline treated breast
      cancer patients.
AB  - BACKGROUND: Taxoids are new chemotherapeutic agents effective in the treatment of
      breast cancer. Paclitaxel treatment has been reported to cause some cardiac side
      effects and both paclitaxel and docetaxel to cause mild, mainly sensory,
      peripheral neuropathy. Autonomic function tests are sensitive measures of
      autonomic neuropathy and cardiac regulation. The purpose of this study was to
      find out whether docetaxel changes neural cardiovascular regulation in breast
      cancer patients previously treated with anthracyclines. PATIENTS AND METHODS:
      Nine women treated for metastatic breast cancer with docetaxel were studied prior
      to the docetaxel treatment and after the third or fourth course. Autonomic
      cardiovascular function tests were performed and heart rate and blood pressure
      variability were assessed with power spectrum analysis. RESULTS: Heart rate
      variability or the heart rate responses to the autonomic function tests did not
      change after docetaxel treatment. The blood pressure response to standing was
      enhanced and systolic blood pressure variability decreased after three to four
      cycles of docetaxel. CONCLUSIONS: Docetaxel treatment did not deteriorate vagal
      cardiac control in breast cancer patients after exposure to epirubicin. The
      observed changes in blood pressure responses suggest that docetaxel changes
      sympathetic vascular control. However, these changes seem to be related to
      altered cardiovascular homeostasis rather than peripheral sympathetic neuropathy.

PMID- 10928150
TI  - Cisplatin sensitivity of ovarian cancer in the histoculture drug response assay
      correlates to clinical response to combination chemotherapy with cisplatin,
      doxorubicin and cyclophosphamide.
AB  - The histoculture drug sensitivity assay (HDRA) has been demonstrated to have high
      predictability for resistance, sensitivity, and survival for gastrointestinal
      cancer (Clin Cancer Res 1: 305-311, 1995; Clin Cancer Res 1: 1537-1543, 1995). In
      this report, we evaluated the clinical usefulness of the HDRA in ovarian cancer.
      HDRA was performed on tumors from patients with ovarian cancer. Eighty-five cases
      (97%) were evaluable. Tumor fragments were cultured on collagen-sponge gels. The
      cultures were incubated with cisplatin (CDDP) for seven days. Cell viability were
      assessed with the MTT end point. The optimal cut off concentration of CDDP was
      determined to be 25 micrograms/ml by correlation with the historical clinical
      response rate to CDDP. HDRA results were correlated to clinical response of 15
      patients who received CDDP-based therapy that included doxorubicin and
      cyclophosphamide (CAP therapy). The true positive rate was 88%, the true negative
      rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate
      prediction rate was 87% when HDRA results were compared to the response of the
      treated patients. The data suggest that the HDRA is capable of predicting the
      response to antitumor chemotherapy in patients with ovarian cancer and that
      measuring response to CDDP can be useful for optimization of CAP chemotherapy for
      patients with this disease.

PMID- 10928151
TI  - p53 as an indicator of lymph node metastases in invasive early colorectal cancer.
AB  - We examined whether overexpression of p53 can be used as a new genetic marker to
      predict the presence of lymph node metastases of early invasive colorectal
      cancer. Forty-nine patients with primary colorectal adenocarcinomas invading to
      the submucosa (sm-CRC) were analyzed and 7 patients were found to have lymph node
      metastases. Immunostaining was used to detect the p53 overexpression; 43% of sm
      CRC stained positive for p53 and all the cancer cells metastasized to lymph nodes
      were p53 positive. Both lymph node involvement and tumor budding were
      significantly more frequent in p53 positive than p53 negative tumors (p < 0.05,
      respectively), and multivariate analysis showed that p53 overexpression
      constituted a higher relative lisk for lymph node metastases of sm-CRC than
      either histologic type, level of sm invasion, macroscopic type, tumor budding or
      vascular invasion, although the difference was not significant (p = 0.086). We
      concluded that p53 overexpression is a useful biological marker of lymph node
      metastases of sm-CRC, and that p53 negative status may be an indicator for
      limited surgery, such as local excision of sm-CRC.

PMID- 10928152
TI  - Usefulness of technetium-99m tetrofosmin mammoscintigraphy as compared to
      mammography for detecting and differentiating palpable breast masses of young
      Taiwanese women.
AB  - Sixty young Taiwanese women with palpable breast masses detected by mammography
      and/or physical examinations underwent technetium-99m tetrofosmin (Tc-TETRO)
      mammoscintigraphy to assess its value for detecting and differentiating breast
      masses. The results showed that 42 of the 45 cases of breast carcinoma were
      detected by Tc-TETRO mammoscintigraphy. Fourteen of the 15 o benign breast
      lesions were differentiated by Tc-TETRO mammoscintigraphy. The diagnostic
      sensitivity, specificity, positive predictive value negative predictive value and
      accuracy of Tc-TETRO mammoscintigraphy were 93% 93% 98% 82% and 93% respectively.
      Thirty-eight of the 45 cases of breast carcinoma were detected by mammography.
      Twelve of the 15 of benign breast lesions were differentiated by mammography. The
      diagnostic sensitivity, specificity, positive predictive value, negative
      predictive value and accuracy of mammography were 84% 80% 93% 63% and 83%
      respectively. We concluded that Tc-TETRO mammoscintigraphy when compared to
      mammography significantly improves the accuracy of detection and differentiation
      of breast cancer in Taiwanese women.

PMID- 10928153
TI  - A multifactorial prognostic model for adult soft tissue sarcoma considering
      clinical, histopathological and molecular data.
AB  - Soft tissue sarcomas (STS) are malignant mesenchymal lesions with a high degree
      of prognostic variability. Different prognostic markers such as grading, staging,
      tumour type and localisation are known. The establishment of these markers was
      based on the evaluation at results of extensive cohorts of patients. Therefore,
      only the established markers provide us with information about probabilities in
      relation to other qualities. Considering as many different markers as possible in
      one prognostic statement should increase the value of the resultant information.
      Therefore, we developed a model involving known prognostic markers to formulate
      an individual prognostic index. In a retrospective analysis, different prognostic
      factors of 198 adult STS patients with histological tumour free resection margins
      were evaluated using a multifactorial analysis. On the basis of a Cox-Regression
      Model with proportional hazards, the prognostic factors (tumour type, staging,
      localisation and type of surgical resection) were selected using previous
      knowledge and a statistical step backward selection procedure adjusting the
      immunohistochemical status of p53/Mdm2 expression. On the basis of the baseline
      survival function of our cohort (S0 (t)), the cumulative probability of survival
      for two S (2) and five S (5) years was estimated. As a result of our analysis the
      equations S (2) = (e-00393)P and S (5) = (e-00869)P can be used to estimate the
      individual two and five-year probability of survival in our cohort. Here p is the
      result of the amount of the estimated regression-coefficients of the exact
      variables of the respective individual patient. This model makes it possible to
      include all the evaluated prognostic factors which, in turn, increases the
      accuracy of the prognostic information for individual patients underlining the
      proportional hazards assumption.

PMID- 10928154
TI  - Survival of glioma patients after complementary treatment with galactoside
      specific lectin from mistletoe.
AB  - Malignant glioma patients were prospectively enrolled into a clinical trial. All
      the patients were provided with the internationally recommended oncologic
      standard treatment (neurosurgery, radiation, basic clinical care according to
      protocol and indication) and randomly divided into a treatment group (receiving
      complementary immunotherapy with a galactoside-specific lectin from mistletoe, ML
      1) and a control group (without additional complementary treatment). Whereas the
      beneficial effects of ML-1 treatment on immunological rescue and quality of life
      have been recently shown, evaluation of relapse free/overall survival was
      performed after a 50 months follow up time. Non-stratified analysis of all the
      patients revealed non-relevant prolongation of relapse-free intervals/overall
      survival time for the treatment group. However, analysis of stratified stage
      III/IV glioma patients demonstrated: 1. a tendency for a prolongation of relapse
      free survival for patients of the treatment group (17.43 +/- 8.2 months) vs. the
      control group (10.45 +/- 3.9 months) 2. a statistically significant (BRESLOW p =
      0.035) prolongation of the overall survival for the treatment group (20.05 +/-
      3.5 months) as compared to the control group (9.90 +/- 2.1 months). These
      promising data warrant confirmation in a GCP-based prospectively randomized
      (multicenter) study, which is currently under consideration.

PMID- 10928155
TI  - Low dose adriamycin and ifosfamide in the treatment of advanced adult soft tissue
      sarcomas.
AB  - BACKGROUND: Soft tissue sarcomas are infrequent tumors (up to 1% of all
      neoplasms) in adult patients. Treatment of advanced disease is largely
      unsatisfactory. Only a few drugs are active agents and combination regimens offer
      limited and short-lived activity. High dose chemotherapy may be administered only
      to limited groups of patients. PATIENTS AND METHODS: We evaluated, in a phase II
      study, the adriamycin and ifosfamide combination regimen. The drugs were
      administered at 60 mg/sqm and 6 g/sqm dosage, respectively. The total number of
      treated patients was 42 of which 40 were evaluable. RESULTS: We observed 6
      complete responses (14% response rate) and 6 partial responses (14%). The mean
      survival was 6 months (median 7.6 months). Toxicity was limited and reversible.
      CONCLUSION: While high dose chemotherapy may be reserved for selected groups of
      patients, an adriamycin and ifosfamide combination regimen at conventional doses
      can be administered to the great majority of patients with suboptimal performance
      status or with advanced age.

PMID- 10928156
TI  - Thymidine phosphorylase expression in gastric cancer in association with
      proliferative activity and angiogenesis.
AB  - BACKGROUND: Thymidine phosphorylase (dThdPase) has been reported to stimulate
      angiogenesis in vivo. We investigated dThdPase expression in gastric cancer in
      association with angiogenesis and proliferative activity. MATERIALS AND METHODS:
      One hundred and forty-eight gastric cancer patients who had received radical
      gastrectomy were investigated. RESULTS: Positive dThdPase staining was observed
      in 98 cases. The microvessel counts for positive and negative cases were 44.1 and
      29.6, respectively, representing a significant correlation. The mean PCNA index
      of positive cases was significantly higher than that of negative cases. The
      patients with positive dThdPase staining in high intensity displayed decreased
      post-operative survival compared to those without. CONCLUSION: Our results
      suggest that proliferative activity of gastric cancer is related to dThdPase
      expression and angiogenesis and that dThdPase expression is associated with
      angiogenesis. dThdPase expression could also be a prognostic factor for gastric
      cancer patients.

PMID- 10928157
TI  - Different fraction schedules and combinations with chemotherapy in radiation
      treatment of non-small cell lung cancer.
AB  - BACKGROUND: In locally advanced non-small cell lung cancer (NSCLC), studies
      demonstrating advantages with hyperfractionated accelerated radiotherapy versus
      conventional radiotherapy have been published, so have studies demonstrating the
      value of chemotherapy concomitantly with radiotherapy. However, the value of non
      conventional fractionation together with concomitant chemotherapy has not been
      investigated. MATERIALS AND METHODS: Consecutive patients from a single
      institution were studied in a retrospective non-randomised fashion. Inclusion
      criteria were stage III NSCLC, treatment with curative intent and a total dose
      above 50 Gy. RESULTS: Eighty-two patients were included and further divided into
      four different treatment groups. Multivariate analysis indicated a survival
      advantage with non-conventional radiotherapy (NCRT), especially if combined with
      concomitant chemotherapy. Toxicity was feasible, however there was a trend
      towards higher toxicity, mainly esophagitis, in patients given concomitant
      chemotherapy with NCRT. CONCLUSION: Our results suggest that accelerated
      hyperfractionated radiotherapy with concomitant chemotherapy could be an
      interesting test-arm in a future prospective study.

PMID- 10928159
TI  - Detection and typing of human papillomaviruses by means of polymerase chain
      reaction and fragment length polymorphism in male genital lesions.
AB  - We investigated the distribution of genital human papillomaviruses (HPVs) among
      171 consenting men of which four were involved twice in this study. The DNA was
      obtained from 7 normal tissues and 168 genital lesions of which 115 were
      diagnosed as condylomata acuminata, 17 as condylomata plana and 36 as HPV
      associated lesions (papules, lichen-like lesions, etc.). The DNA samples were
      analysed for the presence and type of HPV DNA (HPV type 6, 11, 16, 18, 31 or 33)
      by means of polymerase chain reaction (PCR). Out of 175 specimens tested, 140
      (80%) were HPV positive and 35 (20%) HPV negative. There were 81.43% (114 out of
      140) typed HPVs, while 18.57% (26 out of 140) remained untyped. Most samples were
      HPV 6/11 positive (92 out of 114, 80.7%). Restriction fragment length
      polymorphism (RFLP) of HPV 6/11 PCR products in 89.13% (82 out of 92) and 10.87%
      (10 out of 92) specimens corresponded to HPV 6 and HPV 11, respectively. The
      frequency of other HPVs was low, i.e. there were 4.57% (8 out of 175), 1.71% (3
      out of 75) and 0.57% (1 out of 175) HPV type 16, 18 and 33, respectively. There
      were 10 out of 175 (5.71%) cases of multiple HPV infections, of which 6 out of 10
      were cases with HPV 6 and other HPV types. This raises the total prevalence of
      HPV type 6 to 50.29% (88 out of 175) in the study-population. The clinical
      diagnosis condylomata acuminata was preferentially associated with low-risk HPVs
      (types 6 and 11), while other lesions, especially condylomata plana, with high
      risk HPVs (types 16, 18, 31 and 33) and untyped HPVs. The male population,
      indeed, represents a reservoir of HPV infection and directly influences cervical
      cancerogenesis.

PMID- 10928158
TI  - HER-2/neu expression in archival non-small cell lung carcinomas using FDA
      approved Hercep test.
AB  - HER-2/neu is a 185 kDa glycoprotein related to the epidermal growth factor
      receptor. Overexpressed in 25-30% of primary breast carcinomas, HER-2/neu is
      associated with a poor clinical outcome. Recently the FDA approved an antibody to
      HER-2/neu, trastuzumab (Herceptin), for the treatment of HER-2/neu overexpressing
      metastatic breast cancers. Relatively little is known about HER-2/neu status and
      lung cancers. We reasoned that if HER-2/neu status could be ascertained in non
      small cell lung carcinomas (NSCLCs), and a clinical correlation can be
      established, a rationale for the use of Herceptin in this tumor type could be
      established. Using a FDA-approved standardized diagnostic kit, HercepTest, for
      detection of HER-2/neu in clinical specimens, we examined the expression of HER
      2/neu in NSCLCs in archival paraffin-embedded specimens (N = 81). In normal
      epithelium, HER-2/neu expression was not detected in a majority of samples
      (74/81). HER-2/neu overexpression was detected in 27% of the tumors of different
      histological types including adenocarcinomas, large cell carcinomas, and squamous
      cell carcinomas. Poor to moderately differentiated, but not well differentiated
      tumors showed overexpression of HER-2/neu. The specificity of HercepTest was
      further increased (from 27% to 21%) when the expression in the few normal tissues
      was subtracted from the tumor score. HER-2/neu may offer an attractive predictive
      and prognostic factor for NSCLC.

PMID- 10928160
TI  - A phase II study of neuroimmunotherapy with subcutaneous low-dose IL-2 plus the
      pineal hormone melatonin in untreatable advanced hematologic malignancies.
AB  - Interleukin-2 (IL-2) has proven to be able to generate an effective anticancer
      immunity against both solid and hematologic malignancies. Moreover, recent
      advances in the knowledge of psychoneuroimmunology have demonstrated that
      anticancer immunity is under neuroendocrine control and that the pineal hormone
      melatonin (MLT) may stimulate the IL-2-dependent anticancer reaction. Finally,
      preliminary clinical studies have already shown that the concommitant
      administration of MLT may amplify the efficacy of IL-2 in the treatment of
      advanced solid neoplasms, whereas there are no data about MLT influence on IL-2
      activity in hematologic malignancies. The aim of the present study was to
      evaluate the efficacy and tolerability of a neuroimmunotherapeutic combination of
      low-dose IL-2 plus MLT in advanced hematologic malignancies which did not respond
      to previous standard therapies. The study included 12 evaluable patients. Tumor
      histotypes were as follows: non-Hodgkin's lymphoma (NHL) 6; Hodgkin's disease
      (HD), 2; multiple myeloma, 2; acute myelogenous leukemia (ALM), 1 and chronic
      myelomonocytic leukemia (CMML), 1. IL-2 was injected subcutaneously at a dose of
      3 million IU/day for 6 days per week for 4 weeks, corresponding to one cycle. MLT
      was given orally at 20 mg/day in the evening, without interruption. In non
      progressing patients, a second IL-2 cycle was planned after a 3 week-rest period.
      A partial response was achieved in one patient with multiple myeloma. Stable
      disease occurred in 7 other patients (NHL, 3; HD, 1; AML, 1; CLLM, 1; multiple
      myeloma, 1), whereas the other 4 patients progressed. Therefore, lack of
      progression was obtained in 8 out of 12 (67%) patients, with a median duration of
      21+ months (14-30+ months). The treatment was well tolerated in all patients.
      These preliminary results would suggest that the concomitant administration of
      low-dose IL-2 plus the pineal hormone MLT may prolong the survival time in
      untreatable advanced hematologic malignancies, with results comparable to those
      previously reported using a more toxic immunotherapy, consisting of high-dose IL
      2 alone.

PMID- 10928161
TI  - Limitations of detection of bone-marrow micrometastasis in prostate carcinoma
      patients by CK18/PSA immunocytochemistry and PSA RT-PCR.
AB  - BACKGROUND: The aim of this study was to prove the reliability of cytokeratin
      18/prostate specific antigen (CK18/PSA) immunocytochemistry to detect tumor cells
      in the bone marrow of patients with prostate cancer (CaP) compared with a control
      group without CaP. PATIENTS AND METHODS: In bone marrow aspirates of 34 patients
      with CaP and 11 control patients without CaP, CK18/PSA immunocytochemistry was
      performed and compared with PSA RT-PCR in bone marrow and blood. RESULTS: 12% of
      tumors showed a positive staining with PSA and and 17% with CK 18
      immunocytochemistry. There was no correlation with the stage or grade of the CaP.
      False positive results occurred in 2 out of 6 males without CaP and in 2 out of 5
      women. 35% of the samples were found to have PSA-mRNA signals in RT-PCR which
      were neither associated with the histological stage or grade nor the PSA staining
      in immunocytochemistry. CONCLUSION: False positive staining results were obtained
      in control patients. Detection of PSA-mRNA was not associated with
      immunocytochemistry. Neither immunocytochemical nor PCR results were associated
      with the histological stage of the CaP. Thus, detection of micrometastasis using
      immunocytochemical methods has to be interpreted with caution and cannot be
      recommended as a clinical staging procedure.

PMID- 10928162
TI  - Erythrocyte polyamines and prognosis in colorectal cancer patients.
AB  - BACKGROUND: Polyamines play a role in cell proliferation and in cancer
      development: they are mainly carried by red blood cells (RBCs). Abnormally high
      polyamine levels in RBCs have been demonstrated in patients with various types of
      cancer and the prognostic value of RBC polyamine levels has also been underlined.
      Our aims were to compare polyamine levels in RBCs from colorectal adenocarcinoma
      (CRA) patients with those from non neoplastic patients and to evaluate the
      prognostic value of pre-treatment polyamine erythrocyte levels. PATIENTS AND
      METHODS: Sixty-one patients with colorectal cancer and 28 surgical patients
      affected by non neoplastic diseases were included in this study. RBCs polyamine
      levels were evaluated by HPLC. RESULTS: Significantly higher spermidine, spermine
      and total polyamine levels were found in RBCs from CRA patients compared to those
      from control patients. However, there was no significant difference in the
      survival of patients with different polyamine levels. CONCLUSION: Our findings
      show that RBC polyamine levels are not a biologic parameter that may help to
      discriminate between good and poor prognosis in colorectal cancer patients.

PMID- 10928163
TI  - Seroprevalence of Kaposi's sarcoma-associated herpesvirus in healthy adults in
      Israel.
AB  - To determine if Kaposi's sarcoma-associated herpesvirus (KSHV) prevalence is
      correlated with the 9-fold difference in the incidence of classic Kaposi's
      sarcoma observed among Israeli Jewish populations, we conducted a cross-sectional
      KSHV seroprevalence survey in a population of 166 HIV-seronegative healthy
      subjects from the general population (26 women, 140 men). Eight individuals
      (4.8%) (all men) were seropositive for KSHV; differences between men and women
      were not statistically significant. If we consider the sensitivity and
      specificity of the assays, the corrected prevalence would be 6.1% (95% confidence
      interval 2.0-10.1). We noticed a non-statistically 5.5-fold difference between
      individuals above and below 40 years of age, but did not find an association with
      the incidence of classic KS among the Israeli Jewish sub-population, according to
      their origin. This suggests that KSHV is only necessary, albeit not sufficient,
      cause of classic Kaposi's sarcoma.

PMID- 10928165
TI  - Tissue polypeptide specific antigen (TPS) throughout normal pregnancy.
AB  - AIM: TPS concentrations were measured throughout normal pregnancy in maternal
      serum (MS) and amniotic fluid (AF), in order to evaluate the usefulness of TPS in
      the follow-up of pregnancy breast cancer patients. PATIENTS AND METHODS:
      Following informed consent, 30 pregnant women during the 2nd trimester, 28 during
      the 3rd and 26 at parturition were included in the study. For comparison, 28
      women in the 1st trimester and 28 healthy, non pregnant women (controls) were
      also studied. Both MS and AF antigen values were measured by an enzyme
      immunoassay (BEKI Diagnostics). RESULTS: Maternal serum TPS concentrations
      increased significantly with gestational age (p < 0.0001), being significantly
      higher in the 3rd trimester and during labor than those in the controls (p <
      0.0001). Amniotic fluid TPS values were markedly elevated, compared with those in
      MS (p < 0.0001, paired-t-test), declining significantly from the 2nd to the 3rd
      trimester (p < 0.0015) and labor. Both MS and AF TPS values during labor depended
      on the mode of delivery, being higher in the cases terminated by vaginal
      delivery, compared to those by elective cesarean section. CONCLUSION: Maternal
      serum TPS values are influenced significantly by pregnancy, and thus, this
      antigen, as tumor marker seems to be reliable only during early pregnancy.

PMID- 10928164
TI  - High levels of apoptosis are associated with improved survival in non-small cell
      lung cancer.
AB  - Tumour growth is accompanied by angiogenesis and reduced apoptosis in
      experimental animals. The aim of this study was to examine the prognostic value
      of apoptosis and the association between apoptosis and vascularity in non-small
      cell lung cancer (NSCLC). Following in-situ end-labelling of DNA, apoptotic cells
      were quantified by three different indices: as a percentage, either counting
      total cells (AI-tc) or point-counting (AI-pc), or as cells per area (AI-area).
      Blood vessels were stained with vWF antibody and vascularity was quantified by
      three methods. Median values for AI-tc, AI-pc and AI-area were 0.38, 0.32 and
      10.7, respectively. High values were associated with improved survival, reaching
      statistical significance for AI-area (p < 0.05). All three apoptotic indices were
      significantly correlated with each other, but no correlation was found between
      indices of apoptosis and vascularity. As previously reported, vascularity had no
      prognostic value. These results indicate that, in NSCLC, vascularity is not
      informative, but apoptotic index may be a useful prognostic factor.

PMID- 10928166
TI  - The role of Tc-99m methoxyisobutylisonitrile scintimammography as compared to
      mammography in evaluating palpable breast masses of Taiwanese women.
AB  - Eighty-one Taiwanese women (age range 31 to 79 years old) with palpable breast
      masses detected by mammography and or physical examination underwent technetium
      99m methoxyisobutylisonitrile (Tc-99m-MIBI) scintimammography to assess its value
      in the detection of breast carcinomas and their differentiation from benign
      breast masses. The results showed that 58 of the 66 cases of breast carcinoma
      were detected by Tc-99m-MIBI scintimammography. Only 2 our of 15 patients with
      benign breast lesions had an abnormal scintimammographic finding. The mammography
      diagnosed 55 of the 66 cases of breast carcinoma, whilst 8 out of 15 patients
      with benign breast lesions had positive mammographic findings. The diagnostic
      sensitivity specificity and accuracy of Tc-99m-MIBI scintimammography were 88%
      87% and 88%, respectively, whilst these parameters for mammography were 83%, 47%
      and 77%, respectively, regarding the differentiation of malignant from benign
      breast masses. We concluded that Tc-99m-MIBI scintimammography significantly
      improves the sensitivity and specificity for the detection of breast cancer in
      Taiwanese women with dense and small breasts.

PMID- 10928167
TI  - Caffeine-potentiated radiochemotherapy and function-saving surgery for high-grade
      soft tissue sarcoma.
AB  - Caffeine, which has a DNA-repair inhibiting effect, enhances the cytocidal
      effects of anticancer drugs and radiation. We present a preliminary report on the
      results of a new treatment, "radiochemotherapy combined with caffeine" (K3
      protocol), for high-grade soft tissue sarcomas. Seventeen patients with various
      high-grade soft tissue sarcomas were included in this study. Preoperatively,
      three to five courses of intra-arterial chemotherapy using cisplatin, caffeine
      and doxorubicin after radiation therapy were administered. Following the
      preoperative therapy, function-saving surgery was performed for all cases.
      Complete response was observed in six patients, partial response in six and no
      change in five. The effectiveness rate of caffeine-potentiated radiochemotherapy
      was therefore 71%. The histological response for radiochemotherapy was better
      than that for chemotherapy alone, that is, total tumor necrosis was identified in
      six patients and over 90% necrosis in another six. Complications resulting from
      the preoperative radiation comprised of serious inflammation in three patients
      and skin necrosis in another three. Twelve patients have remained free of
      disease, two patients are alive with disease and three have died of metastatic
      disease with a mean follow-up period of 36 months. There was no local tumor
      recurrence. These preliminary findings suggest that caffeine-potentiated
      radiochemotherapy contributed to a satisfactory local response and the success of
      function-saving surgery for high-grade soft tissue sarcomas.

PMID- 10928168
TI  - Immunohistochemical expression of p53 and c-erbB2 proteins in breast cancer in
      Egypt.
AB  - The purpose of the present study was to estimate p53 and c-erbB2 expression in an
      Egyptian cohort and assess their relationships with other indicators of
      aggressive disease. Additionally, the frequency of both oncogenes was compared to
      that reported in other breast cancer populations. Paraffin-embedded tissue
      sections obtained from 210 invasive ductal carcinomas were evaluated
      immunohistochemically for p53 and c-erbB2 oncoproteins using CM-1 polyclonal
      antibody and mAb1 monoclonal antibody, respectively. Tumor proliferation was also
      assessed using PC10 anti-PCNA (proliferation cell nuclear antigen) monoclonal
      antibody. Chi square test was used to assess the relationship between p53 and c
      erbB2 and their associations with other prognostic factors. The results revealed
      that p53 and c-erbB2 were equally expressed, each accounting for 40% of the total
      cases (84 out of 210) Immunoreaction for p53 and/or c-erbB2 was demonstrated in
      65% (136 out of 210) and 15% (32 out of 210) were positive for both oncogenes.
      Poor histologic grade was more significantly associated with p53 expression (P =
      0.0001) than c-erbB2 expression (P = 0.01). The latter was also significantly
      associated with premenopausal status (P = 0.01) and large tumor size (P = 0.003).
      Both p53 and c-erbB2 oncoproteins were found to be unrelated to each other, nodal
      status or PCNA immunostaining. These data suggest that p53 and c-erbB2 oncogenes
      correlate with poor prognostic features of breast cancer. The differences between
      the frequency of p53 and c-erbB2 expression observed in this study and in the
      reports of Western authors will hopefully stimulate investigation of these
      oncogenes using molecular biologic techniques and matched comparative Egyptian
      and European breast cancer groups.

PMID- 10928169
TI  - Super-sensitive prostate-specific antigen (PSA) in serum of women with benign
      breast disease or breast cancer.
AB  - BACKGROUND: Serum prostate-specific antigen (PSA) can be discovered in patients
      with breast cancer. We used ultrasensitive methods of PSA detection, successfully
      developed for early detection of PSA recurrence in prostatic-cancer patients, to
      study PSA in women with breast cancer and benign breast lesions before and after
      surgery. MATERIALS AND METHODS: Blood samples of 45 women with suspect breast
      findings were prospectively analyzed for PSA before and after breast surgery.
      Supersensitive 2nd and 3rd generation DPC assays were used to measure PSA
      (clinical detection limit of > 0.1 and > 0.02 ng/mL, respectively) and combined
      with concentration of serum to improve the clinical detection limit to > 0.025
      and > 0.005 ng/mL, respectively. PSA concentrations were correlated with
      histological findings. RESULTS: The most sensitive detection was required to
      detect PSA preoperatively in 12 out of 45 patients, 8 (31%) out of 26 breast
      cancer patients and 4 (25%) out of 16 patients with benign breast lesions.
      Postoperatively, 13 out of 45 patients were positive for PSA, 7 (27%) breast
      cancer patients and 6 (23%) patients with benign breast lesions. CONCLUSIONS:
      Cancer patients showed the highest concentrations of PSA measured preoperatively
      and a decrease after surgery that was however not significant. Women with breast
      lesions expressed serum PSA in one third of the cases studied. PSA expression in
      serum does not distinguish benign from malignant breast diseases, but it might be
      valuable for follow-up to analyze whether recurrent disease can be detected with
      quantitative ultrasensitive PSA measurement.

PMID- 10928170
TI  - Molecular detection of disseminated cancer cells in the peripheral blood of
      patients with gastric cancer.
AB  - This study was designed to determine whether circulating cancer cells in patients
      with gastric cancer can be identified by a RT-PCR method and to assess the
      clinical significance of the hematogenic dissemination of cancer cell in gastric
      cancer patients. A total of 41 patients with gastric cancer were enrolled in this
      study. Peripheral blood samples from 41 patients with gastric cancer were
      analyzed for CEA mRNA using RT-PCR. Of the 36 patients undergoing radical
      gastrectomy, eight had a positive CEA mRNA signal in their peripheral blood
      before the gastrectomy. In four patients, the CEA mRNA signal was negative,
      positive and then negative again, before, during and after the surgery,
      respectively. Of the five inoperable patients with peritoneal metastasis, four
      had positive CEA mRNA signals despite no metastasis in any other organs. The RT
      PCR method is a useful diagnostic modality to determine patient selection for
      chemotherapy after surgery.

PMID- 10928171
TI  - Integration status of virus DNA and p53 codon 72 polymorphism in human
      papillomavirus type 16 positive cervical cancers.
AB  - BACKGROUND: The aim of this study was to determine the physical state of HPV16
      DNA and to reveal any association between the physical state of virus DNA and
      pathologic or prognostic factors in HPV16 positive cervical cancers. The other
      aim was to estimate the role of p53 codon 72 polymorphism in disease progression.
      MATERIALS AND METHODS: The presence and physical state of HPV16 DNA was analysed
      by Southern blot hybridisation and E1-E2 specific PCRs in the primary tumours and
      pelvic lymph nodes of 85 cervical carcinoma patients. Results Integrated HPV16
      DNA was found in 32 out of 41 (78%) primary tumours and 2 out of 22 (95%) lymph
      nodes carrying HPV16 DNA. No significant association was found between
      integration of virus DNA and course of the disease. There was a trend towards an
      association between disease recurrence and the presence of the p53 codon 72
      arginine homozygous genotype (OR = 3.41, p = 0.23). CONCLUSION: The physical
      state of HPV16 DNA does not seem to play a major role as a prognostic indicator
      in Hungarian cervical cancer patients, while the p53 codon 72 genotype may have
      an impact on the clinical outcome of the disease.

PMID- 10928172
TI  - Infrequent alternations of RB pathway (Rb-p16INK4A-cyclinD1) in adenoid cystic
      carcinoma of salivary glands.
AB  - Retinoblastoma (Rb) tumor suppressor genes' products and of the proteins
      regulating its phosphorylation and function in G1 arrest, p16INK4A and cyclin D1,
      play important roles in the regulation of the cell cycle. Rb gene inactivation,
      reflected by the absence of Rb protein expression, has been reported in oral
      squamous cell carcinomas. p16INK4A is frequently deleted, methylated, or mutated,
      and cyclin D1 gene amplification in many malignancies including oral squamous
      cell carcinomas (SCC). These findings suggested that Rb pathway of G1 arrest are
      the most commonly affected genes in Oral SCC. However, alternation of Rb pathway
      in salivary gland tumors was not clear. In this study, the expressions of Rb,
      p16INK4A, and cyclin D1 alternations were analyzed by immunohistochemical assay
      in 5 specimens of normal salivary glands and twenty-two cases of adenoid cystic
      carcinomas (ACC). Proliferating cell nuclear antigen (PCNA) labelling index
      (P.I.) was used for the evaluation of cell proliferation. Rb was consistently
      expressed in normal salivary glands and ACC. Loss of p16INK4A expression was
      observed in three cases (13.6%) of ACC. And overexpression of cyclin D1 was
      observed in four cases (18.2%). The three p16INK4A absent cases were the tumors
      with predominantly solid pattern and those cases were overexpressed cyclin D1.
      The cell proliferation activities of p16INK4A absent tumors (P.I. = 24.2 +/-
      2.1%) were significantly higher than those of p16INK4A present tumors (P.I. =
      10.4 +/- 3.5%) (P < 0.05). Cyclin D1 expression was also related to cell
      proliferation (P.I. of cyclin D1 negative cases vs. cyclin D1 positive: 10.1 +/-
      3.0% vs. 22.6 +/- 3.4%) (P < 0.05). These findings suggested, however,
      alternations of Rb pathway were infrequent events in ACC of salivary glands and
      inactivation of p16INK4A, cyclin D1 overexpression may be related to the high
      cell proliferating activity of ACC.

PMID- 10928173
TI  - Evaluation of the relationship between serum carcinoembryonic antigen level and
      treatment outcome in surgically resected clinical-stage I patients with non-small
      cell lung cancer.
AB  - The relationship between preoperative serum carcinoembryonic antigen (CEA) level
      and treatment outcome for 39 clinical-stage I patients with surgically resected
      non-small-cell lung cancer (NSCLC) was retrospectively studied. Serum CEA levels
      were measured with an enzyme-linked immunosorbent assay kit, with the upper limit
      of normal defined as 6.7 ng/mL based on the 95% specificity level for benign lung
      disease in our hospital. Patients with serum CEA > or = 6.7 ng/mL (n = 9) were
      more likely to have advanced disease at surgery than those with serum CEA < 6.7
      ng/mL (n = 30) (77.8% vs 16.7%, p = 0.0049). This increase in disease stage at
      surgery was mainly due to mediastinal lymph node metastasis. The sensitivity and
      specificity of serum CEA in the detection of pathological N2 disease were 62.5%
      and 87.1%, respectively. Survival for the high CEA group was significantly worse
      than that for the low CEA group (median survival time, 40.2 vs 75.8 months, p =
      0.0125). Relapse-free survival for the high CEA group was also poorer than that
      of the low CEA group (p = 0.0032). In a multivariate analysis, serum CEA level
      was the most dominant factor affecting relapse-free survival (hazard ratio =
      6.68, p = 0.0053). These findings suggest that preoperative serum CEA level is
      useful not only in detection of mediastinal lymph node metastasis, but also in
      prediction of survival for clinical-stage I patients with NSCLC.

PMID- 10928174
TI  - Prognostic significance of telomeric repeat length alterations in pathological
      stage I-IIIA non-small cell lung cancer.
AB  - This study was performed to evaluate the prognostic significance of alteration in
      telomere length in pathological stage (p-stage) I-IIIA non-small cell lung cancer
      (NSCLC). Paired cancer and normal lung tissues were obtained from 72 patients
      with histologically confirmed p-stage I-IIIA NSCLC. Terminal restriction fragment
      (TRF) length, which indicates telomere length, was measured by Southern blot
      analysis. Tumor telomerase activity was also assayed by non-radioactive PCR-ELISA
      in 55 patients. TRF length (mean +/- SD) in normal tissue was 6.2 +/- 1.1 Kb.
      Therefore, upper and lower limits of normal range in TRF length was set at 8.4
      (mean + 2SD) Kb and 4.0 (mean-2SD) Kb, respectively. A tumor showing TRF length
      over normal range was defined as positive for the alteration. In 72 patients, 25
      (34.7%) with alteration in TRF length had significantly shorter survival
      durations than those of the others. Telomerase activity did not correlate with
      survival duration. In multivariate analysis, alteration in TRF length (P =
      0.0033) was second to p-stage (P = 0.0004) in importance among the various
      parameters.

PMID- 10928175
TI  - Comparison and discrepancy of 18F-2-deoxyglucose positron emission tomography and
      Tc-99m MDP bone scan to detect bone metastases.
AB  - The purpose of this study was to evaluate the usefulness of positron emission
      tomography with 18F-2-deoxyglucose (FDG-PET) for the detection of malignant bone
      metastases, and to compare FDG-PET results with conventional technetium-99m
      methylene diophosphate (Tc-99m MDP) bone scan findings. Twenty-four patients (10
      females, 14 males, ages: 39-71 years) with biopsy-proven malignancy and suspected
      bone metastases, underwent whole body FDG-PET and bone scan to detect bone
      metastases. Bone metastases were established in 39 discordant bone lesions by
      histopathological examination of biopsy samples, MRI/CT, and follow-up bone
      scan/FDG-PET findings showing progressively and extensively widespread bone
      lesions. A total of 98 bone lesions found on either FDG-PET or bone scan were
      evaluated For 39 bone lesions with discordant findings between FDG-PET and bone
      scan, histopathological examination, MRI/CT and follow-up bone scan/FDG-PET
      findings revealed 8 metastatic and 0 benign bone lesions with positive FDG-PET
      findings, not detected on bone scan. Eleven metastatic and 20 benign bone lesions
      with positive bone scan findings were not detected on FDG-PET. FDG-PET has a
      better specificity, but a lower sensitivity for detecting malignant bone
      metastases when compared with bone scan.

PMID- 10928176
TI  - Screening for metastatic disease in newly diagnosed breast cancer patients. What
      is cost-effective?
AB  - BACKGROUND: Significant health care resources are today spent on diagnosing and
      treatment of early breast cancer. MATERIALS AND METHODS: 98 consecutive patients
      referred to our oncological unit between January 1997 and June 1998 underwent an
      evaluation programme including thoracic X-ray, liver and bone scan and blood
      test. When findings suspected for metastatic disease were revealed, further
      examinations (CT-scan, MRI) were performed. RESULTS: Whereas the screening
      programme disclosed four cases (4%) of distant metastasis, several patients had
      to suffer the psychological distress of false positive results. One in three
      suspicious thoracic X-rays, two in two liver scans and 18 out of 21 suspected
      bone scans were concluded false positive in terms of metastatic disease. A
      screening programme including blood test and thoracic X-ray alone, would have mis
      classified one out of 98 patients. CONCLUSION: This study indicated thoracic X
      ray and blood test as being sufficient and 110 Pounds per patient screened could
      be saved.

PMID- 10928177
TI  - Duodenogastric reflux and gastric mucosal polyamines in the non-operated stomach
      and in the gastric remnant after Billroth II gastric resection. A role in gastric
      carcinogenesis?
AB  - BACKGROUND: The relationship between bile reflux and gastric cancer is not
      defined. In order to verify whether a relationship exists, we evaluated the
      duodenogastric reflux and the mucosal polyamines concentration, polycation
      compounds actively involved in cell proliferation, in the non-operated stomach
      and in gastric remnant after Billroth II gastric resection, a precancerous
      condition. MATERIALS AND METHODS: The study was performed on three groups of
      subjects: A) 43 subjects with slight dispeptic symptoms, never operated on; B) 54
      cholecystectomized subjects; C) 38 subjects operated on Billroth II gastric
      resection for duodenal ulcer. Duodenogastric reflux was assessed by measuring the
      concentration of bile acids in gastric juice and expressed as Fasting Bile Reflux
      in micromol/hour. Gastric mucosal polyamine concentration was assessed by High
      Performance Liquid Chromatography and expressed in nmol/mg of proteins. RESULTS:
      The lowest levels of Fasting Bile Reflux (7.95 micromol/hour) and polyamines
      (7.09 nmol/mg proteins) were observed in subjects never operated on. The middle
      values were present after cholecystectomy (Fasting Bile Reflux = 18
      micromol/hour; polyamines = 8.14 nmol/mg proteins). The highest values were
      observed after Billroth II gastric resection (Fasting Bile Reflux = 830
      micromol/hour; polyamines 11.74 nmol/mg proteins) (Kruskal-Wallis test, p =
      0.0001). There was a positive correlation between Fasting Bile Reflux and
      polyamines (Spearman's rank = 0.33; p = 0.0008). CONCLUSIONS: High levels of
      duodenogastric reflux observed after Billroth II gastric resection are associated
      with high polyamine concentration in the gastric mucosa. Bile reflux can be
      considered an important causal factor of the increased risk of gastric stump
      cancer after Billroth II gastric resection.

PMID- 10928178
TI  - Comparison of S100 protein and MIA protein as serum marker for malignant
      melanoma.
AB  - BACKGROUND: Detection of S100 beta in serum has been shown to be a significant
      prognostic marker for malignant melanoma in earlier studies. Melanoma inhibiting
      activity (MIA) has recently been detected as a new serum marker for malignant
      melanoma. MATERIALS AND METHODS: In the present study, serum levels of S100 beta
      protein and MIA were measured over a time period of up to 18 months in 271 serum
      samples from 65 melanoma patients at different stages of disease, during
      chemotherapy and/or immunotherapy. In addition, 46 sera of control patients were
      analysed. The aim of this study was to compare both potential markers. S100 beta
      was measured using the immunoluminometric assay LIA-mat Sangtec (Byk Sangtec
      Diagnostica) with a cut-off level of 0.12 microgram/l. MIA was determined by the
      MIA ELISA kit (Roche) using a cut-off level of 6.5 ng/ml. RESULTS: In 53 patients
      a direct correlation of S-100 values and clinical course could be observed
      (81.5%), whereas in 48 patients MIA-values and clinical course (73.8%) showed an
      association. S100 beta levels were incorrectly elevated in 5 out of 25 sera,
      "false positive" (20%)) and were in 8 out of 40 sera not elevated despite the
      detection of metastases "false negative" (20%)). Assessing the MIA levels, 2 out
      of 25 probes were false positive (8%) and 13 out of 40 probes false
      negative(32.5%). CONCLUSION: Our data strongly suggest that S100 and MIA
      represent serum tumor markers that are valuable both in therapy-monitoring and in
      detection of tumour progression.

PMID- 10928179
TI  - Comparison of different histopathological methods for the examination of sentinel
      lymph nodes in breast cancer.
AB  - BACKGROUND: Sentinel lymphonodectomy is a new method for the classification of
      axillary lymph nodes in breast cancer. The optimum technique for the pathological
      examination of sentinel lymph nodes (SLNs) is still under debate. MATERIALS AND
      METHODS: Different histopathological techniques were evaluated in order to study
      their diagnostic accuracy regarding the detection of metastases in 49 SLNs of 40
      breast cancer patients. RESULTS: In single hematoxylin and eosin (HE) stained
      paraffin sections 18 out of 40 patients showed positive SLNs and 8 out of 40
      showed positive axillary lymph nodes (ALNs). Serial sections with a spacing of
      150 microns between following sections revealed an additional 4 and 5 cases with
      positive SLNs and ALNs, respectively. Single HE frozen sections showed 11 tumor
      positive SLNs among 25 patients. The ultrarapid-immunohistochemistry on single
      frozen sections confirmed these data and detected one additional case with
      isolated tumor cells in the lymph node sinus. CONCLUSION: Histopathological nodal
      staging of SLNs should include serial sections with a spacing of 150 microns
      between sections as well as immunohistochemistry. The ultrarapid
      immunohistochemistry is a sensitive method for the detection of minimal
      metastatic disease in SLNs and can be applied intraoperatively.

PMID- 10928180
TI  - Nonlinear discriminant analysis and prognostic factor classification in node
      negative primary breast cancer using probabilistic neural networks.
AB  - BACKGROUND: We used non-linear kernel discriminant analysis (KDA) to predict the
      outcome of 134 axillary node-negative primary breast cancer patients not treated
      with adjuvant therapy in a non censored database. MATERIAL: Posterior
      probabilities of relapse at 5 years were estimated using probabilistic neural
      networks (PNN) and a cross-validation (leave-one-out) technique to avoid
      overfitting the data. A stepwise method was used to construct the models to
      define the best combination of risk factors among eleven prognostic factors: age,
      menopausal status, Scarff-Bloom-Richardson grade, clinical tumor size,
      pathological tumor size, estrogen and progesterone receptor status, urokinase
      type plasminogen activator, p53 protein level, c-erbB-2 protein and epidermal
      growth factor receptor. The different variables were tested individually and in
      combination to determine their prognostic power using a ROC indicator, which
      measures the separation between the probability distributions of the output
      neuron activations under the null hypothesis (no recurrence at 5 years) and under
      the alternative hypothesis (recurrence at 5 years). RESULTS: The best predictive
      one-dimensional model was obtained with uPA (ROC indicator = 0.75). A two-factor
      model including uPA and clinical tumor size (T) gave the best discrimination
      between recurrence and non recurrence at 5 years (ROC indicator = 0.84).
      Additional variables did not improve the accuracy of the prediction. The uPA-T
      model generated a map useful in predicting the posterior probability of cancer
      recurrence in a given patient. This representation allows the entire database to
      be easily visualized and each patient can be compared with the entire database.
      CONCLUSION: This is a powerful approach to analyze the impact of prognostic
      factors and it could find clinical applications in breast cancer.

PMID- 10928181
TI  - Metaplastic carcinoma of the breast: analysis of eight Asian patients with
      special emphasis on two unusual cases presenting with inflammatory-type breast
      cancer.
AB  - Metaplastic carcinoma of the breast is a rare form of breast cancer and has an
      uncertain prognostic significance. Cases from Asian countries have never been
      reported in the English literature. Between 1983 and 1998, we encountered 8 cases
      in our institution. There were 7 women and one man with a median age of 52.5 (37
      73) years. Pathologic diagnosis included three poorly-differentiated
      adenosquamous carcinomas, two adenocarcinomas with spindle cell metaplasia, two
      matrix-producing carcinomas and one carcinosarcoma. Estrogen receptor was
      positive in 2 (25%) patients. Local recurrence or distant metastasis developed in
      3 patients within one year of initial treatment. With a mean follow-up of 81
      months (range, 19-183 months), 5 patients were disease-free at the time of this
      report. Interestingly, two of our patients had presented with huge-sized
      inflammatory breast cancer and were refractory to neo-adjuvant chemotherapy, but
      enjoyed an unexpected long disease-free survival after mastectomy. Although the
      clinical course of our patients appeared in general similar to that of the
      Western series, the two patients with inflammatory breast carcinoma ran a very
      unusual course, which may deserve further characterization.

PMID- 10928182
TI  - Spontaneous rupture of hepatocellular carcinoma of the caudate lobe.
AB  - A rare case of ruptured hepatocellular carcinoma (HCC) of the caudate lobe is
      reported. A 67-year-old man came to the hospital with complaints of abdominal
      pain and distension. Computed tomography (CT) showed haemoperitoneum and a mass
      in the caudate lobe. Angiography demonstrated a tumor stain. However,
      extravasation of the contrast medium was not clear. Although transcatheter
      arterial embolization (TAE) was performed, bleeding from the tumor could not be
      controlled. The caudate lobe, including the tumor, was resected. The patient died
      of multiple organ failure despite intensive care. This case suggests that TAE is
      not always effective and may not be safely or easily performed when treating
      ruptured HCC in the caudate lobe. This is attributed to the multiple feeding
      arteries of the tumor, derived from the proximal portion of the right and left
      hepatic arteries. If bleeding from the ruptured HCC in the caudate lobe is not
      controlled, immediate resection of the tumor is recommended.

PMID- 10928183
TI  - Second-line chemotherapy with paclitaxel, cisplatin and gemcitabine in pre
      treated sensitive cisplatin-based patients with advanced non-small cell lung
      cancer.
AB  - BACKGROUND: To investigate the safety and effectiveness of the combination of
      paclitaxel, cisplatin and gemcitabine as second-line in patients with advanced
      non-small cell lung cancer (NSCLC) sensitive to first-line cisplatin-based
      chemotherapy. PATIENTS AND METHODS: From June 1997 to December 1998, 26 patients
      with stage IIIB or IV NSCLC received paclitaxel 125 mg/m2, as a one-hour
      infusion, followed by cisplatin 50 mg/m2 and gemcitabine 1000 mg/m2,
      intravenously, on day 1 and 8, every 3 weeks. Twenty-three patients were male;
      the median age was 59 years (range 44-70); The Eastern Cooperative Oncology Group
      performance status was 0 to 1 in 88% of patients; 16 patients had stage IV
      disease and 7 patients had 3 or more sites of disease. The predominant histology
      was adenocarcinoma in 14 patients. Prior treatment involved cisplatin plus
      vinorelbine in 14 patients and cisplatin plus mitomycin C plus vindesine in 12
      cases. RESULTS: Seven (27%; exact 95% confidence limits: 11.6-47.8%) patients
      achieved a partial response to treatment whilst 7 (27%) had stable disease. The
      median duration of response was 22 weeks (range, 18 to 34 weeks). The median
      overall survival was 24 weeks (range, 8 to 36 weeks). The main toxicities were:
      grade 3-4 neutropenia in 9 (34%) patients; grade 2-3 peripheral neuropathy in 10
      (38%); and grade 2-3 asthenia in 15 (57%) cases. CONCLUSION: The paclitaxel,
      cisplatin and gemcitabine combination is active as a second-line regimen in
      patients with advanced NSCLC, but with mild toxicity. It seems suitable for
      patients with advanced NSCLC as a first-line treatment.

PMID- 10928184
TI  - Postoperative radiation therapy for stage IB-IIB carcinoma of the cervix with
      poor prognostic factors.
AB  - BACKGROUND: To investigate failure pattern and to evaluate the prognostic impact
      of lymph node metastasis in patients with cervical cancer treated with
      postoperative adjuvant pelvic irradiation. MATERIALS AND METHODS: Ninety-eight
      patients with FIGO IB to IIB cervical cancer were treated with radical
      hysterectomy, bilateral pelvic lymphadenectomy and postoperative radiation
      therapy. All the patients had at least one of the following pathologic risk
      factors for pelvic recurrence; 1) positive margins, 2) positive pelvic lymph
      nodes other than common iliac node, 3) deep stromal invasion more than 50% or
      parametrial invasion. RESULTS: The 5-year overall survival (OAS) rate for the
      entire patient group was 82%. Causes of the first failure were pelvic recurrence
      in 5 cases and distant metastasis in 15 cases. Fifteen of the 47 patients with
      positive pelvic lymph nodes developed distant metastasis, whereas distant
      metastasis was noted in only 1 of 51 patients without lymph node metastasis. The
      5-year OAS rates for patients with and without pelvic lymph node metastasis were
      76% and 89%, respectively (p = 0.018). CONCLUSION: Despite receiving
      postoperative pelvic irradiation, apparently lower survival was observed for node
      positive patients.

PMID- 10928185
TI  - Cyfra 21-1: a serological help for detection of distant metastases in head and
      neck cancer.
AB  - Local and neck recurrences of squamous cell carcinoma of the head and neck
      (SCCHN) can mostly be detected early when the patient has regular follow-ups.
      Distant metastases though usually remain undiscovered until they produce clinical
      symptoms. Since Cyfra 21-1 correlates with the tumor size and stage in SCCHN, we
      looked for possible connections between Cyfra 21-1 increases and the development
      of distant metastases. The sera of 830 patients with SCCHN were tested for Cyfra
      21-1. The levels were compared with the clinical run of the patients. When Cyfra
      21-1 levels rose above the threshold of 3.3 ng/ml (71 out of 830) staging
      procedures were performed. Tumor growth was found in 50 out of 71 patients with
      elevated Cyfra levels (70.4%). Cyfra serum levels in those cases either
      represented development of distant metastases (27 out of 71), or local and neck
      recurrences. The results of this study show that Cyfra 21-1 is a suitable and
      helpful serological parameter for the follow-up of patients with SCCHN. In the
      event of an elevation of Cyfra 21-1 above the threshold during follow-up, we
      would recommend the performance of a thoracal CT-scan and abdominal omi
      ultrasound as staging procedures.

PMID- 10928186
TI  - Population thiamine status and varying cancer rates between western, Asian and
      African countries.
AB  - The role of food supplements in the form of vitamins has not been extensively
      investigated in relation to varying cancer rates between populations of different
      geographical regions. New data indicate that thiamine (vitamin B1), a common food
      supplement in Western food products, is directly involved in nucleic acid ribose
      synthesis of tumor cells in its biologically activated form through the non
      oxidative transketolase catalyzed pentose cycle reaction. Whether thiamine plays
      a role in increased cancer rates in the Western World by enhancing tumor cell
      proliferation, while increased consumption of thiaminase rich food limiting
      thiamine availability protects against common malignancies in Asia and Africa has
      not been evaluated. In the Western World, thiamine is a popular vitamin
      supplement in the form of tablets and it is also added to basic food items such
      as milled flour, cereals, peanut butter, refreshment drinks and pastas. On the
      contrary, thiaminase, the natural thiamine-degrading enzyme, is abundantly
      present in raw and fermented fish, certain vegetables and roasted insects
      consumed primarily in Africa and Asia. Excess thiamine supplementation in common
      food products may contribute to the increased cancer rates of the Western World.

PMID- 10928187
TI  - Determinants of disability in patients with chronic renal failure.

PMID- 10928188
TI  - Why adolescent medicine?
AB  - This article reviews the biologic, cognitive, and sociocultural changes that
      occur during adolescence. Providing appropriate health care to adolescents in an
      effective manner requires an in-depth understanding of these changes, both in
      terms of preventing the onset of health-risking behaviors and promoting a healthy
      lifestyle. As many chronic diseases of adults have their origins during
      adolescence, this approach holds promise for reducing morbidity and mortality in
      later life as well as during young adulthood. There is an emerging consensus
      regarding the scope and content of preventive services for adolescents. The
      approach to incorporating these services into the health maintenance visit for
      young people is reviewed.

PMID- 10928189
TI  - Getting teenagers to say no to sex, drugs, and violence in the new millennium.
AB  - In the new millennium, teenagers will continue to engage in a wide variety of
      activities that are not healthy for them (e.g., "sex, drugs, and violence").
      Although there is a widely held perception that these are new, modern problems,
      they are not. Appreciating what is normal and abnormal behavior and thinking
      during adolescence, controlling media influences, and giving children and teens
      appropriate and effective drug and sex education will help in understanding
      adolescent behavior and potentially helping them to avoid some of their high-risk
      behaviors.

PMID- 10928190
TI  - Treating acne. A practical guide.
AB  - Acne is the most common skin disorder affecting adolescents. Although there is no
      cure for acne, most patients benefit from currently available medications, and
      most can be managed effectively by the primary care provider. By offering this
      care, the clinician can reduce the emotional burden of acne and help prevent the
      permanent scarring commonly seen in the past.

PMID- 10928191
TI  - Advances in medical management of asthma, headaches, and fatigue.
AB  - The 1990s in medicine have been characterized by the development of various
      clinical guidelines to assist in the diagnosis, classification, and management of
      common disorders. Among the most frequent presenting complaints of adolescent
      patients are asthma, headaches, and fatique. In an era of managed care and brief
      clinical encounters, application of standardized guidelines, modified
      appropriately for adolescents, is likely to improve clinical outcomes, including
      patient and parent satisfaction. In each of these disorders, engaging the
      adolescent patient as a partner in planning and implementing management is
      crucial to success.

PMID- 10928192
TI  - Adolescent menstrual disorders. Update.
AB  - Menarche is an important event during adolescence. For most girls, it marks
      successful progression through puberty and the onset of reproductive capability.
      Confidential and sensitive discussion of growth and development, body image,
      menstrual function, and sexual behavior is an important component of the annual
      health examination. Menstrual problems are common during adolescence and
      frequently require evaluation and intervention. Although most problems are
      explained by maturation of the hypothalamic-pituitary-ovarian axis, organic
      pathology must always be considered and excluded in a logical and cost-effective
      manner.

PMID- 10928193
TI  - Sexually transmitted diseases in adolescents.
AB  - Sexually transmitted diseases (STDs) are among the top 10 reportable diseases in
      the United States. Of the more than 12 million cases annually, approximately 3
      million occur in adolescents. An estimated two thirds of cases occur in
      individuals younger than age 25. Almost half of adolescents report ever being
      sexually active, and approximately one third are currently sexually active. For a
      number of biologic and psychosocial reasons, sexually active adolescents have the
      highest rate of STDs of any sexually active age group. They suffer from the acute
      manifestations of these diseases as well as complications that place them at risk
      for some significant long-term negative sequelae, such as infertility, chronic
      pelvic pain, and cancer. This article reviews the reasons for this increased risk
      and provides updates on the common STDs that affect adolescents.

PMID- 10928194
TI  - Recognizing and treating anxiety and depression in adolescents. Normal and
      abnormal responses.
AB  - Recognition of depressive and anxiety disorders in adolescents reduces morbidity,
      mortality, and lifetime risk for psychiatric illness and maladaptive behaviors.
      Effective treatments for these disorders are available and are associated with
      minimal severe side effects. Because adolescents tend to underreport their
      psychologic distress, screening for these disorders in the primary care setting
      is incumbent on the clinician. Depression or anxiety may be a primary or a
      secondary condition--with each other and with other medical illness. Substance
      abuse, including cigarettes, should not be overlooked as an accompanying risk
      factor for poor health care habits and as an indicator of degree of family (lack
      of) support. Adolescents at risk should be screened and their symptoms taken
      seriously. This brief overview does not focus on the need for primary care
      clinicians to seek assistance and support of psychiatrists in the diagnosis and
      development of treatment algorithms. All clinicians should be reminded that
      judgments about peoples' internal mental states and function are difficult to
      assess objectively and with compassion. Initial assessment in the primary care
      setting should include a telephone consultation with a reliable psychiatric
      colleague and referral for more in-depth evaluation in the event of more
      complicated course. These disorders need to be treated comprehensively because of
      the lifelong implications that having a chronic disease bear on the individual
      and his or her physiology. Primary care clinicians are pivotal instruments in
      engaging adolescents to embrace appropriate therapeutic measures for their
      current and future health.

PMID- 10928195
TI  - Contraception.
AB  - Prescribing and reviewing contraceptive methods with adolescents involves a
      significant amount of time and resources. Health care providers need to be
      familiar with how teens think about sex and birth control, what their beliefs
      are, and how individual teens may make different choices based on their
      lifestyles. Barrier methods remain popular in that they are accessible and do not
      require a clinician visit. The hormonal choices need to be explained fully in
      plain language and selections based on these sessions made appropriately. Teens
      can be effective users of contraception if they are given the appropriate tools,
      access, and knowledge.

PMID- 10928196
TI  - Diagnosis and treatment of teen drug use.
AB  - Small but significant decreases in adolescent abuse of tobacco, alcohol, and
      marijuana in recent national surveys allow clinicians to feel some optimism about
      defeating the specter of substance abuse. It appears that changing the perception
      of risk and increasing adolescent disapproval of substance abuse are key goals.
      For every adolescent, reducing risk factors while identifying and enhancing
      protective factors optimizes an individual's opportunity to avoid potentially
      harmful behaviors. While focusing energy and commitment on each adolescent,
      however, clinicians cannot ignore the need for wider social change because the
      proximal adolescent domains of individual, family, and school factors are
      interrelated and embedded in the community and societal contexts. Every sector in
      society plays a crucial role in preventing adolescents from experimenting with
      and continuing to abuse tobacco, alcohol, or illicit drugs, from parents,
      physicians, educators, and policy makers to every adult invested in the health
      and well-being of adolescents.

PMID- 10928197
TI  - Is it juvenile rheumatoid arthritis or fibromyalgia?
AB  - For the clinician evaluating adolescents with chronic musculoskeletal pain and
      fatigue, the distinctions between JRA and FS are clear based on physical
      examination findings. The two conditions can coexist. For the patient with an
      initial diagnosis of either JRA or FS whose clinical response to therapy is not
      in keeping with expectations or physical examination findings or whose clinical
      course worsens without explanation, reevaluation to determine if FS in the JRA
      patient has developed or JRA in the FS patient has emerged is warranted. Until
      clinicians have a better understanding of the intricacies of the neurohormonal
      and immunologic systems and how they affect somatic symptoms, they can continue
      to provide patients with a treatment plan based on current knowledge that should
      minimize patients' discomfort and allow them to have appropriately functional
      lives.

PMID- 10928198
TI  - Sports injuries in adolescents.
AB  - Musculoskeletal injuries are the most common injuries in youth sports. A number
      of growth-related factors unique to the adolescent age group play an important
      role in the epidemiology, types, and management of these injuries. These mainly
      relate to the physical and psychosocial growth and development during adolescence
      and are discussed in this article. Overuse injuries are more commonly seen in
      this age group in the primary care setting. Shoulder impingement, elbow and
      shoulder injuries related to throwing, stress injuries of the wrist,
      spondylolysis, and anterior knee pain are some of the overuse injuries reviewed
      in this article.

PMID- 10928199
TI  - Acute and chronic pelvic pain in female adolescents.
AB  - Pelvic pain in adolescents is a common and frequently puzzling symptom with many
      possible causes. The patients who suffer from this symptom, by and large, have
      diagnosable and treatable causes. A sensible, studied, and progressive approach
      by a warm and accepting physician usually is the key to successful diagnosis and
      management of this condition.

PMID- 10928200
TI  - Eating disorders in adolescents and young adults.
AB  - Eating disorders are relatively common and frequently result in medical signs and
      symptoms. Armed with an appreciation of the protean manifestations of these
      complex health problems as well as an appreciation of the biopsychosocial
      approach needed to help the adolescent or young adult woman recover, the primary
      care physician is in an excellent position to have a therapeutic role in the
      recovery from these chronic conditions. By recognizing the medical aspects of
      eating disorders, the oversimplified viewpoint of considering them as purely
      psychiatric disorders can be avoided. Open and consistent communication with
      patients, with a focus on health rather than dysfunction and mental illness,
      facilitates the acceptance of a comprehensive approach in which the internist,
      dietitian, and mental health provider all have a role.

PMID- 10928201
TI  - Self-reported adherence to antiretroviral medications among participants in HIV
      clinical trials: the AACTG adherence instruments. Patient Care Committee &
      Adherence Working Group of the Outcomes Committee of the Adult AIDS Clinical
      Trials Group (AACTG).
AB  - This paper describes the AACTG Adherence Instruments, which are comprised of two
      self-report questionnaires for use in clinical trials conducted by the Adult AIDS
      Clinical Trials Group (AACTG). The questionnaires were administered to 75
      patients at ten AACTG sites in the USA. All patients were taking combination
      antiretroviral therapy (ART), including at least one protease inhibitor. Eleven
      per cent of patients reported missing at least one dose the day before the
      interview, and 17% reported missing at least one dose during the two days prior.
      The most common reasons for missing medications included 'simply forgot' (66%)
      and a number of factors often associated with improved health, including being
      busy (53%), away from home (57%) and changes in routine (51%). Less adherent
      patients reported lower adherence self-efficacy (p = 0.006) and were less sure of
      the link between non-adherence and the development of drug resistance (p =
      0.009). They were also more likely to consume alcohol, to be employed outside the
      home for pay and to have enrolled in clinical trials to gain access to drugs (all
      p < 0.05). Twenty-two per cent of patients taking drugs requiring special
      instructions were unaware of these instructions. Each questionnaire took
      approximately ten minutes to complete. Responses to the questionnaires were
      favourable. These questionnaires have been included in six AACTG clinical trials
      to date and have been widely disseminated to investigators both in the USA and
      abroad.

PMID- 10928202
TI  - AIDS education for gay men: towards a more cognitive approach.
AB  - An approach to AIDS education is presented that focuses on the thinking processes
      which accompany gay men's decisions to engage in high-risk sex. It is proposed
      that: (1) at the time they are deciding to have high-risk sex, gay men generally
      engage in an 'internal dialogue' that justifies this decision to themselves; (2)
      the AIDS-related thinking underpinning such self-justifications can differ
      appreciably from the AIDS-related thinking that takes place outside the sexual
      context; and (3) AIDS education can profitably exploit this difference between
      'heat of the moment' and 'cold light of day' thinking. Evidence supporting these
      proposals is drawn from studies in which gay men who had engaged in unprotected
      anal intercourse recalled the occasion concerned in detail, including any self
      justifications they had used; and from controlled intervention studies, in which
      gay men who had engaged in unprotected anal intercourse were confronted with the
      thinking they had employed in the heat of the moment.

PMID- 10928203
TI  - The role of theory in HIV prevention.
AB  - There is growing evidence that well designed, targeted, theory-based behaviour
      change interventions can be effective in reducing the spread of HIV. Although
      each behaviour is unique, there are only a limited number of theoretical
      variables that serve as the determinants of any given behaviour. Understanding
      these variables and their role in behavioural prediction can guide the
      development of effective behaviour change interventions. This paper will describe
      and define these variables and show how they can be used in the development of
      behavioural interventions.

PMID- 10928204
TI  - Sexual dysfunction in gay and bisexual men with HIV infection: evaluation,
      treatment and implications.
AB  - Sexual dysfunction problems are common in people with HIV infection, but their
      relevance has been recently highlighted in response to the increased survival
      shown by many individuals with HIV, and the publicity surrounding the development
      of new treatments for male sexual dysfunction. Thirty-four gay/bisexual men with
      HIV infection presenting with sexual dysfunction were assessed. Antiretroviral
      combination therapy including protease inhibitors was taken by 44%, other
      combinations not including protease inhibitors by 24%, while 32% were not taking
      any antiretrovirals. Primarily psychogenic sexual dysfunction was thought to be
      present in 44%, primarily organic dysfunction in 22% and a mixed aetiology in
      34%. Treatments offered included psychological interventions and physical methods
      of treatment, alone or in combination. Treatment was effective, with 76%
      reporting resolution of the problems, 14% reporting improvement and only 10%
      reporting no change. Practical and ethical issues raised by the findings are
      discussed.

PMID- 10928205
TI  - Do gay men discuss HIV risk reduction with their GP?
AB  - In September/October 1997, 1,004 gay men using one of five gyms in central London
      completed a confidential anonymous questionnaire which included items on sexual
      as well as steroid-related injecting behaviour and whether they had ever
      discussed these behaviours with friends, sexual partners or a general
      practitioner (GP). Nearly all the men reported having had sex with another man in
      the previous six months, while a quarter had had unprotected anal intercourse in
      the previous three months. Less than one-third of the men (30%) had discussed
      safer sex with their GP, compared with 92% who had talked about it with friends
      and 87% with lovers (p < 0.001). Of those who had discussed safer sex with their
      GP, one in six (17%) had not found it easy--this was significantly higher than
      the proportion who had not found it easy to discuss safer sex with friends,
      lovers or casual partners (3-9%, p < 0.01). More than 10% of the men had ever
      injected anabolic steroids. Of those who had injected anabolic steroids, just
      over one-third (36%) had ever discussed this with their GP. It appears that the
      majority of gay men in this study had not discussed HIV risk reduction with their
      GP. Until obstacles to discussing risk reduction and HIV prevention are overcome,
      the routine consultation in general practice will not be able to fulfill its
      potential for health promotion.

PMID- 10928206
TI  - Stressors and strengths among women living with HIV/AIDS in New York City.
AB  - We conducted face-to-face interviews with a non-probability sample of 373 women
      living with HIV/AIDS in New York City. Most were indigent African-Americans and
      Latinas (M age = 39.61 years). Participants reported considerable stressors. For
      example, 59% (n = 221) had been sexually abused and 69% (n = 258) physically
      abused at some point in their lives. In the past 30 days, 9% reported having
      injected drugs. However, participants also reported considerable strengths,
      including high levels of spirituality, mastery and HIV-related social support.
      Multivariate analyses indicated these resources were generally associated with
      less depressive symptomatology. Findings suggest the need for thorough
      psychosocial evaluations of women living with HIV to facilitate psychological
      adaptation, including an exploration of their strengths and culturally-based
      competencies.

PMID- 10928207
TI  - HIV as identity, experience or career.
AB  - Issues of treatment compliance and the relationship between treatments, optimism
      and sexual practice are best understood when living with HIV is conceptualized as
      a dynamic process requiring individuals to work on their subjectivity. In an
      interview study of 76 people living with HIV/AIDS in Australia, three 'modes of
      subjectification' were identified: HIV as identity, HIV as experience and HIV as
      career. The impact of treatments on individuals was mediated by the relationship
      of HIV to selfhood and to community, and took different forms under each mode of
      subjectification. HIV as identity was most characteristic of gay men and resulted
      in failures of compliance or of safe sex being felt as failures of the self. HIV
      as experience was particularly characteristic of women and heterosexual men and
      was associated with a less regimented view of treatment compliance and no
      association between treatments optimism and sexual practice. HIV as career,
      characteristic of both gay men and others, was associated with hyper-compliant
      treatment practice and context-dependent sexual practice.

PMID- 10928208
TI  - Consent and antenatal HIV testing: the limits of choice and issues of consent in
      HIV and AIDS.
AB  - The mood of nihilism that affected HIV is now changing. The availability of new
      therapies allows for cautious optimism--especially in relation to mother-to-child
      transmission of HIV and preventative interventions. This has prompted a
      widespread policy shift towards HIV testing in pregnancy. In this context,
      informed consent is an ethical issue which needs to be addressed. This study
      reports on two sets of data exploring consent policy and practices in UK
      antenatal clinics. The first is derived from an audit of obstetric clinics in the
      UK and Eire (n = 288), with a 91% response rate. The second provided the views on
      consent and testing of a cohort of pregnant women attending four London antenatal
      clinics (n = 697). It was found that written consent was more likely to be
      obtained in units with a universal HIV testing offer (p = 0.0005); 77.8% of women
      believed consent would be requested, but 17.7% believed they could not refuse an
      HIV test. Their views were contrasted with those held about other antenatal
      screening tests. The data show that the generally haphazard method of giving
      information and obtaining consent in antenatal HIV provision is probably
      counterproductive in terms of test uptake and the ultimate goal of minimizing
      maternal-fetal HIV transmission.

PMID- 10928209
TI  - First injection and current risk factors for HIV among new and long-term
      injection drug users.
AB  - The purpose of this paper is to estimate HIV seroprevalence and to examine the
      injection and sexual risk behaviours of a cohort of active new heroin injectors
      who have initiated injection within the past four years and to compare their risk
      behaviours with those of long-term heroin injectors who initiated injection prior
      to January 1, 1985. A stratified network-based sample was used to recruit
      injection drug users (IDUs) from the streets of Miami-Dade, Florida. New IDUs
      displayed a significantly lower HIV seroprevalence than long-term injectors (13.3
      versus 24.7%). Both new and long-term drug injectors exhibited a high level of
      current HIV risk behaviour. While new injectors were more likely than long-term
      injectors to practise safer injection behaviours at the initial injection
      episode, the current risk behaviours of new and long-term injectors are similar.

PMID- 10928210
TI  - Cost-effectiveness of an HIV risk reduction intervention for adults with severe
      mental illness.
AB  - Small-group HIV prevention interventions that focus on individual behavioural
      change have been shown to be especially effective in reducing HIV risk among
      persons with severe mental illness. Because economic resources to fund HIV
      prevention efforts are limited, health departments, community planning groups and
      other key decision-makers need reliable information on the cost and cost
      effectiveness (not solely on effectiveness) of different HIV prevention
      interventions. This study used an economic evaluation technique known as cost
      utility analysis to assess the cost-effectiveness of three related cognitive
      behavioural HIV risk reduction interventions: a single-session, one-on-one
      intervention; a multi-session small-group intervention; and a multi-session small
      group intervention that taught participants to act as safer sex advocates to
      their peers. For men, all three interventions were cost-effective, but advocacy
      training was the most cost-effective of the three. For women, only the single
      session intervention was cost-effective. The gender differences observed here
      highlight the importance of focusing on gender issues when delivering HIV
      prevention interventions to men and women who are severely mentally ill.

PMID- 10928211
TI  - The changing pattern of mental health problems in HIV infection: the view from
      London, UK.
AB  - As we end the second decade with AIDS, profound changes in our understanding of
      its aetiology, mechanism of disease and its treatment have led to significant
      improvements in survival, disease progression and quality of life for those
      individuals with HIV infection who are fortunate enough to have access to health
      care and to treatments for the infection and its complications. Unsurprisingly,
      the psychological and social consequences of HIV have also seen important shifts,
      giving rise to new and unforeseen difficulties, as well as a greater sense of
      hope. Here, some of the changes seen among people with HIV infection being looked
      after in a Central London teaching hospital and referred to the mental health
      services are reviewed and discussed.

PMID- 10928212
TI  - Gender differences in behavioural and psychosocial predictors of HIV testing and
      return for test results in a high-risk population.
AB  - We assessed gender differences in psychosocial and behavioural predictors of HIV
      testing and returning for results in a high-risk sample of 1,049 predominately
      minority, impoverished, homeless and/or drug-abusing women (n = 621) and men (n =
      428). Predictors included latent variables representing injection drug use, self
      esteem, social support, AIDS knowledge, poor access to health services, perceived
      risk for AIDS, sexual risk behaviour and the mediators of positive and negative
      coping styles. Significant predictors of test and return for women included
      injection drug use, greater social support, more AIDS knowledge, a higher
      perceived risk for AIDS and a positive coping style. Significant predictors for
      the men included injection drug use, greater AIDS knowledge, a higher perceived
      risk for AIDS and a positive coping style. Although greater social support was
      not significant for the men, the significant predictors of HIV testing and return
      were generally similar for the men and women. However, the men evaluated their
      risk of AIDS significantly lower than the women, although they reported more
      sexual risk behaviours and equally risky injection drug use behaviours. Results
      suggest that interventions designed to increase AIDS knowledge, to raise the
      perception of risk and to promote a positive coping style would be effective in
      encouraging more HIV testing for both men and women, but raising perceptions of
      what constitutes personal risk behaviours may need special emphasis when
      delivering prevention programmes to men.

PMID- 10928213
TI  - Stage of change versus an integrated psychosocial theory as a basis for
      developing effective behaviour change interventions. The Project RESPECT Study
      Group.
AB  - According to the Stages of Change (SOC) model, behavioural change involves a
      process of movement from precontemplation (no intention to change), to
      contemplation (some intention to change, but no behaviour), to preparation
      (intention to change and early inconsistent behavioural attempts to change), to
      action (consistent behavioural performance for less than six months) and finally,
      to maintenance (consistent behavioural performance for six months or more).
      Moreover, it is argued that cognitive (e.g. attitude change) and action oriented
      (e.g. changing self-efficacy) strategies are differentially effective at
      different stages. In contrast, most other behavioural prediction and change
      models suggest that both cognitive and action oriented approaches are necessary
      to move people from precontemplation to contemplation (i.e. to develop
      intentions). This paper tests this and other differences between these two
      theoretical approaches. Among other findings, our data indicate that a
      combination of cognitive and action strategies may be the most effective way to
      target individuals who have no intention to change their behaviour.

PMID- 10928214
TI  - Functional analysis of dynamin isoforms in Drosophila melanogaster.
AB  - Dynamin and dynamin-like proteins are required for endocytosis, synaptic vesicle
      recycling and membrane trafficking. From the shibire locus in Drosophila
      melanogaster, six different isoforms of dynamin are generated by alternative
      splicing. However, the roles of the individual isoforms in cellular processes are
      unknown. To investigate functional differences among the dynamin isoforms,
      transgenic lines were generated that individually expressed each of 3 different
      isoforms under UASGAL4 control. The expression of the isoforms was controlled by
      neural promoter (elav)-driven GAL4, or by a shibire-promoter driven GAL4
      transgene. Reporter gene expression indicated that the shi promoter is active
      during embryogenesis, and in larvae, pupae, and adults in a pattern consistent
      with normal dynamin expression. To assay for the ability of dynamin isoforms to
      function in vivo, the isoforms expressed via these GAL4 drivers were tested for
      the ability to rescue shibire phenotypes. When expressed at very high levels all
      individual isoforms tested rescued the temperature-sensitive paralytic phenotype
      of shi(ts2) flies; however, this rescue was partial, suggesting that no single
      tested isoform is sufficient for synaptic vesicle recycling in vivo. When tested
      for ability to rescue lethality induced by heat-pulsing larvae during
      development, shi- promoter driven expression of individual isoforms conferred
      significant resistance to heat treatment during larval development. However, all
      3 isoforms were unable to rescue the lethality of shi12-12B mutants which are
      severely hypomorphic (or null) for shibire function. Taken together, these
      observations suggest that individual shibire isoforms have specific molecular
      activities in vivo.

PMID- 10928215
TI  - Spectral sensitivity of wild-type and mutant Drosophila melanogaster larvae.
AB  - Wild-type (Canton-S) Drosophila melanogaster larvae are generally repelled by
      white light. Mutant larval photokinesis A (lphA) larvae are less strongly
      repelled than controls. Mutant Larval photokinesis B (LphB) larvae are
      unresponsive to light, as are larvae from LI2, an isofemale line whose
      progenitors were recently derived from a natural population. To characterize the
      behavior of larvae from the mutant stocks and the isofemale line more precisely,
      we determined the range of wavelengths that repel wild-type (Canton-S) D.
      melanogaster larvae and identified wavelengths to which larvae are most
      sensitive. In comparison to adult flies, Canton-S larvae are much less sensitive
      to white light and respond to a narrower range of wavelengths. The wavelengths to
      which Canton-S larvae are maximally sensitive are 500 nm (green), 420 nm
      (indigo), and 380 nm (ultraviolet). Mutant lphA larvae respond abnormally to
      green and indigo light but are as strongly repelled by ultraviolet light as
      controls. In contrast, mutant LphB larvae and larvae from the LI2 isofemale line
      are unresponsive to green, indigo, or ultraviolet light. Thus, lphA larvae have a
      wavelength-specific defect, while LphB and LI2 larvae are generally unresponsive
      to wavelengths that repel wild-type larvae.

PMID- 10928216
TI  - A phenylalanine hydroxylase gene from the nematode C. elegans is expressed in the
      hypodermis.
AB  - We have identified an aromatic amino acid hydroxylase gene from the nematode C.
      elegans that likely encodes the worm phenylalanine hydroxylase (PheH). The
      predicted amino acid sequence is most similar to that of other PheH and TrpH
      proteins. Reporter gene fusions and staining with an antibody to mammalian PheH
      indicate the gene is expressed in hypodermal cells. A fusion protein expressed in
      bacteria can convert phenylalanine to tyrosine, and, to a lesser extent,
      tryptophan to 5-hydroxytryptophan. We hypothesize that the protein is necessary
      to produce additional tyrosine for protein cross-linking in the nematode cuticle.

PMID- 10928217
TI  - Biochemical measurements of bone turnover in children and adolescents.
AB  - Biochemical measurements of bone turnover are helpful in the study of the
      pathophysiology of skeletal metabolism and growth. However, interpretation of
      their results is difficult because they depend on age, pubertal stage, growth
      velocity, mineral accrual, hormonal regulation, nutritional status, circadian
      variation, day-to-day variation, method of expression of results of urinary
      markers, specificity for bone tissue, sensitivity and specificity of assays.
      Three markers of bone formation have been described including their bone
      specificity and age-related changes: osteocalcin, alkaline phosphatase and its
      skeletal isoenzyme, procollagen I extension peptides. Bone resorption markers
      (hydroxyproline; deoxypyridinoline; pyridinoline; peptides containing these
      crosslinks such as N-telopeptide to helix in urine (NTX), C-telopeptide-1 to
      helix in serum (ICTP) and C-telopeptide-2 in urine and serum (CTX); tartrate
      resistant acid phosphatase; hydroxylysine and its glycosides) are described with
      special attention to methodologic issues, mainly ways of expression of their
      results. Changes of bone turnover during growth are described during four
      periods: infancy, prepubertal period, puberty and the postpubertal period.
      Pubertal changes of bone markers are described with special attention to gender
      differences and hormonal mechanisms of the growth spurt which determine
      differences related to the pubertal stage. Disturbances of bone turnover in four
      conditions are described to illustrate the impact of such diseases on growth and
      formation of peak bone mass: prematurity, malnutrition, growth hormone deficiency
      and corticosteroid-treated bronchial asthma. Available data suggest biochemical
      markers of bone remodeling may be useful in the clinical investigation of bone
      turnover in children in health and disease. However, their use in everyday
      clinical practice is not advised at present.

PMID- 10928218
TI  - Differences in the capacity of several biochemical bone markers to assess high
      bone turnover in early menopause and response to alendronate therapy.
AB  - We measured bone mineral density (BMD), four markers of bone formation [bone
      alkaline phosphatase (bAP), osteocalcin (Oc), N- and C-terminal propeptide of
      type I procollagen (PINP and PICP respectively)] and five markers of bone
      resorption [serum C-terminal telopeptide of type I collagen (CTx), urinary CTx, N
      terminal cross-linked telopeptide (NTx), free and total deoxypyridinoline (fDpd
      and tDpd respectively)] in 28 healthy premenopausal women (45.7 +/- 3.0 years),
      15 early (< 7 years) healthy menopausal women (53.8 +/- 3.1 years) and 20
      osteoporotic women (65.3 +/- 8.2 years). Bone markers and BMD were also measured
      in the osteoporotic women 4.1 +/- 0.2 and 12.6 +/- 1.2 months after the beginning
      of alendronate therapy (Fosamax, 10 mg/day) respectively (BMD in 16/20). We
      calculated the intra-individual coefficient of variation (iCV) and the least
      significant change (LSC) for each bone marker from a subset of 9 healthy
      premenopausal women (32 +/- 5 years) who had a first and a second morning void
      urine collection (FMV and SMV respectively) and a blood sample on 4
      nonconsecutive days (mean interval 14 +/- 3 days). None of the bone markers was
      correlated with BMD (except p = 0.043 between serum Oc and hip BMD). All markers,
      except fDpd, were increased significantly in early menopausal women when compared
      with the premenopausal group. Serum CTx presented the highest increase at
      menopause (+67.8%) and identified the highest rate (11/15) of early menopausal
      women with bone turnover above the premenopausal range. The iCVs for bone
      formation markers (7.2-14.4%) were lower than those for bone resorption markers
      (14.6-22.3%). The iCVs obtained on FMV and SMV were not different. The decrease
      after 4 months of alendronate was significant for each bone marker but variable
      from one marker to another. Serum CTx showed the largest decrease (70.8%) and
      identified the highest number of biologically responding patients (change > LSC;
      n = 17/20). A significant change in serum CTx after 4 months of alendronate was
      the best predictor of a significant gain in spine BMD (i.e., > or = 27 mg/cm2)
      after 1 year of therapy, allowing 15 of 16 patients (94%) to be classified
      correctly (one false-positive). Urinary NTx/Cr was the second best predictor.
      Despite a moderately high iCV (20.6%), serum CTx appeared the most effective of
      the markers tested and could be of interest for the detection of high bone
      turnover and the longitudinal monitoring of alendronate therapy in the individual
      patient. It must be stressed that serum PINP and urinary NTx and tDpd compared
      very similarly with serum CTx for monitoring alendronate therapy.

PMID- 10928219
TI  - Cross-sectional area of lumbar vertebrae in peri- and postmenopausal patients
      with and without osteoporosis.
AB  - The purpose of this study was to analyze the midvertebral area of lumbar
      vertebrae in osteoporotic and nonosteoporotic female patients and to find out
      whether the midvertebral area may be used as an additional parameter in the
      diagnosis of osteoporosis. In 195 peri- and postmenopausal patients (average age
      51.7 +/- 5.2 years) trabecular and cortical bone mineral density (BMD) were
      determined using quantitative CT (QCT) in L2-4. In addition, midvertebral cross
      sectional area was measured in a standardized fashion on the CT sections and the
      height of the second lumbar vertebra was determined on the lateral digital
      radiographs. Body height and weight were obtained and vertebral fracture status
      was determined. According to WHO criteria 29 patients (average age 57.2 years)
      were considered osteoporotic, 93 osteopenic (average age 52.2 years) and 73
      normal (average age 48.6 years). Body weight and size did not show significant
      differences between the individual groups. Average midvertebral area was 1278 +/-
      173 mm2 in the osteoporotic patients, 1186 +/- 125 mm2 in the osteopenic patients
      and 1126 +/- 127 mm2 in the normals. A correlation of r = -0.39 (p < 0.05) was
      obtained between BMD and area. Thirty-six of 195 patients showed osteoporotic
      vertebral fractures. Midvertebral area in these patients was 1266 +/- 171 mm2
      versus 1159 +/- 133 mm2 in the nonfractured females (p < 0.05). We therefore
      conclude that the lumbar midvertebral area is larger in osteoporotic and
      osteopenic patients compared with women with normal BMD. In contrast to
      biomechanical considerations midvertebral area seems not to be suited as an
      additional measure of bone strength in vivo.

PMID- 10928220
TI  - Occupational activity and bone mineral density in postmenopausal women in
      England.
AB  - Few studies have assessed the relationship between occupational activity and bone
      mineral density (BMD), although two case-control studies have reported a
      protective effect of occupational activity on hip fracture. In the present study
      580 postmenopausal women aged 45-61 years completed a risk factor questionnaire
      including a detailed occupational history. For each job, hours spent sitting,
      standing, walking, lifting and carrying were recorded; these measures, evaluated
      at ages 20, 30, 40 years, in the current job and over the working lifetime, were
      used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and
      measurements at five sites were used in a multiple regression analysis adjusting
      for potential confounding variables. There was a significant negative association
      between sitting at age 20 years and BMD at the radius (p = 0.037), with negative
      relationships of borderline significance at the anteroposterior spine (p = 0.091)
      and whole body (p = 0.078). There were significant positive associations between
      standing at age 30 years and BMD at all five sites (p < 0.05), but no significant
      linear associations for standing at ages 20 and 40 years. No significant
      associations were found for lifetime or current occupational measures of sitting,
      standing, walking and lifting or carrying. The lack of consistency of these
      significant findings suggests that they may have occurred by chance, and that
      occupational activity has little if any effect on BMD in postmenopausal women.

PMID- 10928221
TI  - Temperature dependency of quantitative ultrasound.
AB  - Quantitative ultrasound (QUS) parameters are temperature dependent. We examined
      the effect of temperature on QUS using Lunar Achilles+ and Hologic Sahara units.
      In vivo studies were performed in a cadaveric foot and in 5 volunteers. QUS scans
      were performed in the cadaveric foot, using both machines, at temperatures
      ranging from 15 to 40 degrees C. To assess the effect of change in water bath
      temperature in the Achilles+, independently of foot temperature, 5 volunteers
      were studied at water temperatures ranging from 10 to 42 degrees C. In the
      cadaveric foot there were strong negative correlations between temperature and
      speed of sound (SOS) but a moderately positive correlation between temperature
      and broadband ultrasound attenuation (BUA). Stiffness and the Quantitative
      Ultrasound Index (QUI) in the cadaveric foot showed strong negative correlations
      with temperature, reflecting their high dependence on SOS. In the 5 volunteers,
      in whom foot temperature was assumed to be constant, there was a small change in
      Stiffness in the Achilles+, with variation in water temperature. In conclusion,
      while there are opposite effects of temperature on SOS and BUA in vivo, there is
      still a significant effect of temperature variation on Stiffness and the QUI.
      This may have clinical significance in particular subjects. The precision of QUS
      may be affected by temperature variation of the environment or of the patient's
      limb. Instruments utilizing a water bath may be able partly to compensate for
      changes in environmental temperature, but standardization of water bath
      temperature is crucial to maximize precision.

PMID- 10928222
TI  - Can the WHO criteria for diagnosing osteoporosis be applied to calcaneal
      quantitative ultrasound?
AB  - With the increasing number of quantitative ultrasound (QUS) devices in use
      worldwide it is important to develop strategies for the clinical use of QUS. The
      aims of this study were to examine the age-dependence of T-scores and the
      prevalence of osteoporosis using the World Health Organization Study Group
      criteria for diagnosing osteoporosis and to examine the T-score threshold that
      would be appropriate to identify women at risk of osteoporosis using QUS. Two
      groups of women were studied: (i) 420 healthy women aged 20-79 years with no
      known risk factors associated with osteoporosis; (ii) 97 postmenopausal women
      with vertebral fractures. All subjects had dual-energy X-ray absorptiometry (DXA)
      measurements of the spine and hip and QUS measurements on three calcaneal
      ultrasound devices (Hologic Sahara, Hologic UBA575+, Osteometer DTUone). A
      subgroup of 102 (76 on the DTUone) healthy women aged 20-40 years was used to
      estimate the young adult mean and SD for each QUS and DXA measurement parameter
      to calculate T-scores. The age-related decline in T-scores for QUS measurement
      parameters was half the rate observed for the bone mineral density (BMD)
      measurements. The average T-score for a woman aged 65 years was -1.2 for QUS
      measurements and -1.75 for the BMD measurements. When osteoporosis was defined by
      a T-score < or = -2.5 the prevalence of osteoporosis in healthy postmenopausal
      women was 17%, 16% and 12% for lumbar spine, femoral neck and total hip BMD
      respectively. When the same definition was used for QUS measurements the
      prevalence of osteoporosis ranged from 2% to 8% depending on which ultrasound
      device and measurement parameter was used. Four different approaches, based on
      DXA-equivalent prevalence rates of osteoporosis, were utilized to examine which T
      score threshold would be appropriate for identifying postmenopausal women at risk
      of osteoporosis using QUS measurements. These ranged from -1.05 to -2.12
      depending upon the approach used to estimate the threshold and on which QUS
      device the measurements were performed, but all were significantly lower than the
      threshold of -2.5 used for BMD measurements. In conclusion, the WHO threshold of
      T = -2.5 for diagnosing osteoporosis requires modification when using QUS to
      assess skeletal status. For the three QUS devices used in this study, a T-score
      threshold of -1.80 would result in the same percentage of postmenopausal women
      classified as osteoporotic as the WHO threshold for BMD measurements.
      Corresponding T-score thresholds for individual measurement parameters on the two
      commercially available devices were -1.61, -1.94 and -1.90 for Sahara BUA, SOS
      and estimated heel BMD respectively and -1.45 and -2.10 for DTU BUA and SOS
      respectively Additional studies are needed to determine suitable T-score
      thresholds for other commercial QUS devices.

PMID- 10928223
TI  - Prevention of bone loss with risedronate in glucocorticoid-treated rheumatoid
      arthritis patients.
AB  - The aim of the study was to assess risedronate's effect on bone mineral density
      in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We
      carried out a two center, 2 year, double-masked, placebo-controlled trial with a
      third year of nontreatment follow-up. We studied 120 women requiring long-term
      glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with
      daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of
      12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine
      (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while
      significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p
      < 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss
      in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone
      mass decreased significantly (-3.6%, p < 0.001). The difference between placebo
      and daily 2.5 mg risedronate groups was significant at the lumbar spine (p =
      0.009) and trochanter (p = 0.02) but did not reach statistical significance at
      the femoral neck. Although not significantly different from placebo at the lumbar
      spine, the overall effect of the cyclical regimen was similar to that of the
      daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the
      risedronate groups that was significant at the lumbar spine. A similar number of
      patients experienced adverse events (including upper gastrointestinal events)
      across treatment groups and risedronate was generally well tolerated. Thus
      risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis
      receiving glucocorticoids while patients receiving a placebo have significant
      bone loss.

PMID- 10928224
TI  - Susceptibility to osteoporotic fracture is determined by allelic variation at the
      Sp1 site, rather than other polymorphic sites at the COL1A1 locus.
AB  - Previous studies have identified an association between osteoporotic fracture and
      a polymorphism affecting a Sp1 binding site in the first intron of the collagen
      type I alpha 1 gene (COL1A1). It is currently unclear, however, whether this
      association is direct or the result of linkage disequilibrium with other
      polymorphisms situated nearby. In this study we analyzed the relationship between
      four well-characterized single-nucleotide polymorphisms at the COL1A1 locus and
      osteoporotic fracture in 93 patients with vertebral fracture and 88 age-matched
      controls randomly selected from the community. We studied a MspI polymorphism 26
      kb upstream of the COLIA1 gene, the Sp1 binding site polymorphism in intron 1, a
      RsaI polymorphism in intron 5 and a MnlI polymorphism in exon 52. The Sp1 and
      RsaI polymorphisms were in strong linkage disequilibrium (chi 2 = 77.87, p <
      0.001) and weaker linkage disequilibrium was detected between the Sp1 and MnlI
      polymorphisms (chi 2 = 5.54, p < 0.025). There was a significant association
      between COL1A1 haplotypes that included the Sp1 and RsaI polymorphisms and
      fracture (p < 0.05-0.001), but no association with haplotypes that included only
      the MspI and MnlI polymorphisms. This association with fracture was strongest
      when haplotypes were grouped by Sp1 alleles (chi 2 = 11.15, d.f. = 1; p = 0.001).
      Furthermore, logistic regression analysis showed that of all the polymorphisms
      tested, only the Sp1 binding site polymorphism acted as an independent predictor
      of fracture: odds ratio [95% CI] = 2.26 [1.09-4.69]. These data suggest that it
      is the Sp1 polymorphism rather than other polymorphisms at the COL1A1 locus which
      act as a marker for osteoporotic fractures.

PMID- 10928225
TI  - Bone loss in long-term survivors after transplantation of hematopoietic stem
      cells: a prospective study.
AB  - Organ transplantation is associated with relevant bone loss. Bone loss of up to
      20% of pretransplant bone mineral density (BMD) values within the first year
      after kidney, liver, heart and lung transplantation has been reported. Patients
      undergoing transplantation of hematopoietic stem cells provide an interesting
      model to study transplantation-induced bone loss, especially because most
      patients do not have preexisting bone disease. A longitudinal study was performed
      in 81 patients undergoing bone marrow or peripheral blood stem cell
      transplantation. BMD was determined by dual-energy X-ray absorptiometry before
      transplantation, at discharge from the hospital, and at 6 and 12 months after
      transplantation in all 81 patients. In 35 patients BMD was re-evaluated 24 months
      after transplantation. Vitamin D and parathyroid hormone, bone alkaline
      phosphatase as a marker of bone formation, and N-terminal telopeptide of type I
      collagen as a marker of bone resorption were assessed before transplantation and
      in the short-term follow-up 14 and 28 days after transplantation. The majority of
      patients (72%) showed normal BMD before transplantation. However, lower BMD was
      observed in patients who had received high-dose cytoreductive chemotherapy before
      transplantation compared with those who had received no chemotherapy or only
      hydroxyurea. Despite supplementation with elemental calcium (1000 mg/day) and
      vitamin D (1000 IU/day), the mean rate of bone loss during the first year was 7.2
      +/- 6.3% at the lumbar spine, 11.9 +/- 8.1% at the femoral neck and 3.8 +/- 2.5%
      at the total body compartment. Evaluation of the pattern of bone loss during the
      first year demonstrated that the amount of bone loss was largest within the first
      40 days after transplantation and small during the second half of the first year
      after transplantation. The majority of patients showed vitamin D deficiency and
      secondary hyperparathyroidism. Bone formation was normal before and after
      transplantation, whereas bone resorption was dramatically increased before and
      after transplantation. Exposure to glucocorticoids was associated with higher
      bone loss at spine and femoral neck but not at the total body compartment. Our
      data demonstrate rapid bone loss in patients undergoing transplantation of
      hematopoietic stem cells. Bone turnover is characterized by biochemical
      uncoupling of bone resorption and bone formation, changes interestingly pre
      existing before transplantation. The observed alterations in bone mass and
      metabolism emphasize the importance of clinical trials with antiresorptive agents
      to prevent and treat post-transplantation osteoporosis in this group of patients.

PMID- 10928226
TI  - Assessment of a new quantitative ultrasound calcaneus measurement: precision and
      discrimination of hip fractures in elderly women compared with dual X-ray
      absorptiometry.
AB  - The incidence of osteoporotic hip fracture increases in postmenopausal women with
      low hip bone mineral density (BMD). Dual X-ray absorptiometry (DXA) is the most
      commonly used technique for the assessment of bone status and provides good
      measurement precision. However, DXA affords little information about bone
      architecture. Quantitative ultrasound (QUS) systems have been developed to
      evaluate bone status for assessment of fracture risk. Our study was designed to
      assess a new QUS system from Hologic, the Sahara; to compare it with a previous
      model, the Walker-Sonix UBA 575+; and to investigate whether it is able to
      discriminate between women with and without fracture. Using both ultrasound
      devices, the measurements were performed at the heels of 33 postmenopausal women
      who had recently sustained hip fracture. A control group of 35 age-matched
      postmenopausal women was recruited for comparison. The total, neck and trochanter
      femoral BMD values were assessed using DXA for both groups. QUS and DXA
      measurements were significantly lower in fractured patients (p < 0.005) than in
      the control group. The short-term, mid-term and standardized short-term
      precisions were used to evaluate the reproducibility of the two QUS systems. The
      Sahara showed a better standardized coefficient of variation for broadband
      ultrasound attenuation (BUA) than did the UBA 575+ (p < 0.001). The correlation
      of BUA and speed of sound (SOS) between the two QUS devices was highly
      significant, with an r value of 0.92 for BUA and 0.91 for SOS. However, the
      correlation between DXA and ultrasound parameters ranged from 0.28 to 0.44. We
      found that ultrasound measurements at the heel were significant discriminators of
      hip fractures with odds ratios (OR) ranging from 2.7 to 3.2. Even after adjusting
      the logistic regressions for total, neck or trochanter femoral BMD, QUS variables
      were still significant independent discriminators of hip fracture. The areas
      under the ROC curves of each ultrasound parameter ranged from 0.75 to 0.78, and
      compared very well with femoral neck BMD (p > 0.05). In conclusion, our study
      indicated that the calcaneal QUS variables, as measured by the Sahara system can
      discriminate hip fracture patients equally as well as hip DXA.

PMID- 10928227
TI  - In situ femoral dual-energy X-ray absorptiometry related to ash weight, bone size
      and density, and its relationship with mechanical failure loads of the proximal
      femur.
AB  - The objective of this study was to directly compare in situ femoral dual-energy X
      ray absorptiometry (DXA) and in vitro chemical analysis (ash weight and calcium)
      with mechanical failure loads of the proximal femur, and to determine the
      influence of bone size (volume) and density on mechanical failure and DXA-derived
      areal bone mineral density (BMD, in g/cm2). We performed femoral DXA in 52 fixed
      cadavers (age 82.1 +/- 9.7 years; 30 male, 22 female) with intact skin and soft
      tissues. The femora were then excised, mechanically loaded to failure in a stance
      phase configuration, their volume measured with a water displacement method
      (proximal neck to lesser trochanter), and the ash weight and calcium content of
      this region determined by chemical analysis. The correlation coefficient between
      the bone mineral content (measured in situ with DXA) and the ash weight was r =
      0.87 (standard error of the estimate = 16%), the ash weight allowing for a better
      prediction of femoral failure loads (r = 0.78; p < 0.01) than DXA (r = 0.67; p <
      0.01). The femoral volume (r = 0.61; p < 0.01), but not the volumetric bone
      density (r = 0.26), was significantly associated with the failure load. The
      femoral bone volume had a significant impact (r = 0.35; p < 0.01) on the areal
      BMD (DXA), and only 63% of the variability of bone volume could be predicted
      (based on the basis of body height, weight and femoral projectional bone area.
      The results suggest that accuracy errors of femoral DXA limit the prediction of
      mechanical failure loads, and that the influence of bone size on areal BMD cannot
      be fully corrected by accounting for body height, weight and projected femoral
      area.

PMID- 10928228
TI  - Is a calculated total hip BMD of clinical use?
AB  - The diagnosis of osteoporosis is based on bone mass measurement. To avoid the
      errors associated with the measurement of spinal bone density the total hip has
      been accepted as the standard measurement site. This information is not available
      for many early measurements. We have assessed whether it is possible to derive
      clinically useful information about total hip bone mineral density (BMD) from
      measurements at other hip sites. The bone mass measurements of 46 patients
      participating in a current trial of therapy for osteoporosis were reviewed. The
      total hip BMD as directly measured was compared with that obtained from the
      formula: Total hip BMD = 0.48 x Neck BMD + 0.62 x Trochanteric BMD + 0.03. In 30
      patients with follow-up data the rate of change in hip BMD over a year was also
      determined by both methods. In the pretreatment state there was good agreement
      between the two measures (r2 = 0.96, SEE 0.012 g/cm2). If the formula was used to
      compute a change in total hip BMD, the agreement between both methods remained
      good. However, the standard error of the estimate of the change represented 59%
      of the observed change. This indicates that the error associated with this
      estimate is too great to allow clinically meaningful conclusions to be drawn from
      calculated total hip BMD. We conclude that, whilst it may be possible to obtain
      reasonable point estimates of total hip BMD from other measures in the hip, these
      estimates are too imprecise to allow conclusions about change in BMD to be made.

PMID- 10928229
TI  - Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring
      of HbA1c.
AB  - The monitoring of diabetic patients by evaluating glycated protein levels is now
      widely accepted and performed. The microchromatographic version of the high
      performance liquid chromatography method is the technique most frequently used in
      clinical practice. The DCA 2000 instrument (Bayer Diagnostics, Milan, Italy),
      based on an immunochemical technique, has been proposed for the rapid and simple
      evaluation of HbAlc, using even capillary blood. We evaluated 171 subjects
      including 22 healthy volunteers, 78 type 2 diabetic patients with different
      degrees of metabolic control, 11 women affected by gestational diabetes mellitus
      (GDM), 6 patients with hyperlipemia, 38 patients with chronic renal failure, 13
      diabetic patients with chronic renal failure, and 3 patients with
      hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system.
      Data from within-run imprecision studies showed excellent precision, for both DCA
      2000 and the HPLC system. The correlation between the two different systems, as
      shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923).
      Results from the control group and diabetic patients were used to compare the two
      methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001)
      than those obtained with the HPLC system, in both healthy subjects and diabetic
      patients. To detect possible interferences, selected samples were analyzed from
      patients with hyperlipemia, diabetes and chronic renal failure, and
      hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation
      coefficient between the two systems was confirmed (y = 1.047x - 1.236, r =
      0.876), in the case of chronic renal failure the correlation turned out to be
      very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000
      gives accurate and reliable results in the clinical field of interest.

PMID- 10928230
TI  - Polymorphonuclear leukocyte membrane fluidity before and after activation in
      subjects with insulin resistance.
AB  - The aim of this research was the evaluation of polymorphonuclear leukocyte (PMN)
      membrane fluidity in subjects with insulin resistance. Insulin sensitivity, in
      fact, may be influenced by plasma membrane fluidity. We enrolled 19 subjects with
      insulin resistance previously demonstrated during an euglycemic hyperinsulinemic
      clamp. PMN membrane fluidity was studied by labeling intact cells with the
      fluorescent probe 1-[4-(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene and
      calculating the fluorescence polarization degree. The measurement was made before
      and after incubation of PMNs with two activating agents: 4-phorbol 12-myristate
      13-acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). The baseline
      data showed a reduction of PMN membrane fluidity in subjects with insulin
      resistance. After PMN activation with PMA and fMLP, no significant variation in
      membrane fluidity was present in PMNs from normals, while in those from subjects
      with insulin resistance a slight decrease in PMN membrane fluidity was found only
      after activation with fMLP. The behavior of PMN membrane fluidity, before and
      after activation, distinguishes insulin-resistant subjects from normal controls,
      although the effect cannot be directly correlated with the degree of insulin
      resistance.

PMID- 10928232
TI  - Prospective study of development of microalbuminuria and retinopathy in Brazilian
      IDDM patients.
AB  - With the aim to study potential risk factors for the development of
      microalbuminuria and retinopathy, baseline characteristics were examined in 50
      Brazilian IDDM patients followed for 4.48 years with a 2-year reexamination.
      During the study, 3 patients (6%) aged 25.9 +/- 4.4 years, duration of diabetes
      8.1 +/- 4.2 years, died from acute complications without microalbuminuria and
      retinopathy after a follow-up of 2.1 +/- 0.7 years. The standardized mortality
      rate for the group was 0.84 per 1000 (95% CL, 0.31, 1.83) in comparison to 0.14
      per 1000 in the general population. From 34 normoalbuminuric individuals at
      baseline (urinary albumin excretion rate (AER) < or = 20 micrograms/min in > or =
      2 overnight urine collections), 10 developed microalbuminuria with an incidence
      density of 6.5 cases per 100 person-years (95% CL, 2.23, 10.16). Spontaneous
      normalization of AER was found in 2 of 4 patients with microalbuminuria at cycle
      2. Multiple stepwise regression analysis demonstrated that baseline AER (p =
      0.03), but not glycated hemoglobin, blood pressure or duration of diabetes,
      predicted end-of-study AER. From 36 patients without retinopathy, 10 developed
      nonproliferative retinopathy with an incidence density of 6.6 cases per 100
      person-years (95% CL, 2.75, 10.54). Retinopathy was associated with duration (p =
      0.05) and age at diagnosis of diabetes (p = 0.01). A tendency with baseline AER
      (p = 0.06) was also noted. No patient developed macroalbuminuria, proliferative
      retinopathy or hypertension. By the end of our study, in a cohort of young IDDM
      patients followed in a developing country, 6% died from acute complications and
      15 patients (44.1%) developed retinopathy and/or microalbuminuria. Our results
      suggest that the only predictor of end-of-study AER was baseline AER. Also,
      duration of diabetes and age at diagnosis appear to be risk factors for
      retinopathy.

PMID- 10928231
TI  - Intensive insulin therapy combined with metformin in obese type 2 diabetic
      patients.
AB  - Unlike other pharmacological therapies used in obese type 2 diabetic patients,
      metformin has been shown to improve glycemic control with lower insulin levels
      and not to involve weight gain. We therefore examined the effect of adjunct
      metformin in 13 severely obese type 2 diabetic patients (BMI 39.3 +/- 3.9 kg/m2)
      in suboptimal glycemic control pretreated with intensified insulin therapy.
      Patients were randomly assigned to either metformin or placebo treatment (double
      blind) for 10 weeks and after a 2 week washout period received the opposite
      treatment, respectively, for 10 additional weeks. HbA1c decreased comparably
      during placebo (from 8.1 +/- 0.4 to 7.6 +/- 0.3%) and metformin (from 8.5 +/- 0.4
      to 7.4 +/- 0.3%, p = 0.29 vs. placebo). Changes in fasting glucose levels were
      also not different between placebo (from 9.3 +/- 0.7 to 9.5 +/- 0.7 mM) and
      metformin (from 10.3 +/- 0.5 to 9.5 +/- 0.6 mM, p = 0.44 vs. placebo). Total
      exogenous insulin requirements decreased from 53 +/- 10 to 35 +/- 7 units during
      metformin treatment (p = 0.02 vs. placebo). Changes in fasting insulin levels
      during placebo and metformin treatments were not different (p = 0.11). Metformin
      had no effect on body weight and serum triglycerides but marginally decreased
      serum cholesterol levels (from 239 +/- 18 to 211 +/- 14 mg/dl, p = 0.005, p =
      0.08 vs. placebo). During the oral glucose tolerance test no differences were
      observed in the areas under the curve for glucose and insulin while that for C
      peptide showed a tendency to increase during metformin administration. We
      conclude that addition of metformin to insulin treatment in severely obese type 2
      diabetic patients improves glycemia but not hyperinsulinemia in comparison to
      intensive insulin therapy alone. With adjunct metformin, approximately 30% less
      exogenous insulin is required. With respect to glycemia and lipids, adjunct
      metformin can be a reasonable treatment alternative in selected obese patients
      with type 2 diabetes already on intensive insulin therapy.

PMID- 10928233
TI  - Cationic determinants of D-fructose insulinotropic action.
AB  - In the absence of any other exogenous nutrient, D-fructose stimulates insulin
      release from rat pancreatic islets provided that it is tested at high
      concentrations in excess of a threshold value close to 80 mM, an optimal
      secretory response being recorded at 240 mM. In the present study, the cationic
      determinants of the insulinotropic action of D-fructose, used at the latter high
      concentration, were explored in perifused rat islets that had been prelabelled
      with either 86Rb or 45Ca. The changes in 86Rb outflow and 45Ca efflux evoked by
      240 mM D-fructose were comparable to those caused by 11.1 mM D-glucose in that
      both hexoses inhibited 86Rb and 45Ca outflow and, at normal Ca2+ concentration,
      caused a secondary rise in 45Ca efflux. These cationic changes coincided with
      stimulation of insulin release. The major differences between the two series of
      experiments consisted, in the islets exposed to D-fructose, in the occurrence of
      an early and transient increase in 45Ca efflux at normal extracellular Ca2+
      concentration, a secondary reascension in 86Rb outflow and a dramatic off
      response in both 86Rb and 45Ca outflow as well as insulin release. These
      phenomena were also observed in islets exposed to 240 mM 3-O-methyl-D-glucose,
      suggesting that they may be linked to the massive influx (or efflux) of
      monosaccharides, as possibly accompanied by Na+ inward co-transport, mobilization
      of Ca2+ from intracellular stores and activation of voltage- and/or Ca(2+)
      sensitive K+ channels. This interpretation was supported by the finding that, at
      high concentrations (80.0 mM) of D-glucose or D-mannose, the aldohexoses also
      provoked a reascension in 86Rb outflow and off-response in insulin release. The
      cationic determinants of the insulinotropic action of D-fructose, in high
      concentration (240 mM), thus appear similar, if not identical, to those currently
      incriminated in the stimulation of insulin release by D-glucose.

PMID- 10928234
TI  - Lipid peroxidation in nicotinamide-deficient and nicotinamide-supplemented rats
      with streptozotocin-induced diabetes.
AB  - Reactive oxygen species have been related to the pathogenesis of various
      diseases, including diabetes mellitus. Nicotinamide has been used for the
      prevention of the diabetogenic effects of streptozotocin (STZ) in animals. In the
      present study we assessed the effect of diets with deficient, normal or 17-fold
      supplemented nicotinamide concentrations on the rate of lipoperoxidation in
      animals with STZ-induced diabetes. Male Wistar rats were divided into three
      groups kept on one of the diets for six weeks: DD, diabetic rats on a
      nicotinamide-deficient diet; DN, diabetic rats on a normal nicotinamide diet; and
      DS, diabetic rats on a nicotinamide-supplemented diet. During the fourth week of
      the experiment all animals were fasted for 24 hours and injected into the tail
      vein with a single STZ dose (40 mg/kg weight). Eight animals from each of the six
      groups were then sacrificed 24 hours, 1 week and 2 weeks after STZ injection.
      Mean pancreatic thiobarbituric acid reactive substances (TBARS) (nmol/mg tissue)
      were significantly lower in the DS group (p < 0.05) compared to the DN and DD
      groups at 24 hours and during the first week. Hepatic TBARS concentrations
      (nmol/mg protein) did not differ between groups. Mean hepatic reduced glutathione
      (GSH) levels were significantly higher (46.76 +/- 12.33 nmol/mg protein) in the
      DS group compared to the DD (32.90 +/- 6.70) and DN (24.55 +/- 6.41) groups, but
      only after the 24-hour period. Hepatic vitamin E consumption (microgram/g tissue)
      was considerable in the groups not supplemented with nicotinamide, whereas
      vitamin E levels were unchanged in the supplemented group. In contrast, plasma
      vitamin E levels were decreased in the normal and supplemented groups after 1 and
      2 weeks. A higher N-methylnicotinamide excretion (microgram/24 hours) occurred in
      the supplemented group. We conclude that, after induction of diabetes with STZ,
      nicotinamide supplementation protected from the damage caused by the toxic action
      of STZ, promoting lower lipid peroxidation.

PMID- 10928235
TI  - Improved postprandial glycaemic control with insulin Aspart in type 2 diabetic
      patients treated with insulin.
AB  - The effect on postprandial blood glucose control of an immediately pre-meal
      injection of the rapid acting insulin analogue Aspart (IAsp) was compared with
      that of human insulin Actrapid injected immediately or 30 minutes before a test
      meal in insulin-treated type 2 diabetic patients with residual beta-cell
      function. In a double-blind, double dummy crossover design, patients attended
      three study days where the following insulin injections in combination with
      placebo were given in a random order: IAsp (0.15 IU/kg body weight) immediately
      before the meal, or insulin Actrapid (0.15 IU/kg) immediately (Act0) or 30
      minutes before (Act-30) a test meal. We studied 25 insulin-requiring type 2
      diabetic patients, including 14 males and 11 females, with a mean age of 59.7
      years (range, 43-71), body mass index 28.3 kg/m2 (range, 21.9-35.0), HbA1c 8.5%
      (range, 6.8-10.0), glucagon-stimulated C-peptide 1.0 nmol/l (range, 0.3-2.5) and
      diabetes duration 12.5 years (range, 3.0-26.0). Twenty-two patients completed the
      study. A significantly improved postprandial glucose control was demonstrated
      with IAsp as compared to Act0, based on a significantly smaller postprandial
      blood glucose excursion (IAsp, 899 +/- 609 (SD) mmol/l.min versus Act0, 1102 +/-
      497 mmol/l min, p < 0.01) and supported by a significantly lower maximum serum
      glucose concentration (Cmax) up to 360 min after dosing (IAsp, 10.8 +/- 2.2
      mmol/l vs. Act0, 12.0 +/- 2.4 mmol/l, p < 0.02). No difference was demonstrated
      in glucose endpoints between IAsp, administered with a meal and Actrapid injected
      30 minutes before the meal (AUCglucose IAsp, 899 +/- 609 mmol/l min vs. Act-30,
      868 +/- 374 mmol/l min; Cmax IAsp, 10.8 +/- 2.2 mmol/l vs. Act-30, 11.1 +/- 1.8
      mmol/l). No concerns about the safety of IAsp were raised. Immediate pre-meal
      administration of the rapid-acting insulin analogue Aspart in patients with type
      2 diabetes resulted in an improved postprandial glucose control compared to
      Actrapid injected immediately before the meal, but showed similar control
      compared to Actrapid injected 30 minutes before the meal. These results indicate
      that the improved glucose control previously demonstrated with insulin Aspart
      compared to human insulin in healthy subjects and type 1 diabetic patients also
      applies to insulin-treated type 2 diabetic patients.

PMID- 10928236
TI  - The effect of a single bout of exhaustive exercise on muscle carbohydrate and
      lipid metabolism in a rat model of type 2 diabetes mellitus.
AB  - The aim of the present study was to estimate whether a single bout of exhaustive
      exercise influences the glycogen and triglyceride (TG) content in red and white
      gastrocnemius muscle and in the liver of rats with experimental type 2 diabetes.
      Experiments were carried out on male Wistar rats fed from 8 to 11 weeks of age
      with isocaloric standard or high-fat diet (HFD) with a previous injection of low
      dose of streptozotocin (STZ) or vehicle at 2 days of age (I, control group; II,
      HFD; III, STZ; IV, STZ + HFD). Group IV (STZ + HFD) represents a model of type 2
      diabetes. Basal liver glycogen was markedly lower in all the studied groups
      compared to controls. Glycogen concentration after exercise fell significantly in
      the examined tissues in all groups in comparison to basal conditions. A
      significant TG accumulation in examined tissues was observed in all the studied
      groups in comparison to controls. Exercise decreased tissue TG content in all the
      groups, but it remained significantly higher in the experimental groups vs.
      control. We conclude that in this model of type 2 diabetes, a single bout of
      exercise reveals defective utilization of tissue carbohydrates and lipids.

PMID- 10928237
TI  - The procession of times and paradigms.

PMID- 10928238
TI  - A new human science for the new millennium?

PMID- 10928239
TI  - From isolated minds to experiential worlds: an intersubjective space odyssey.
AB  - This paper recasts psychoanalysis as a post-Cartesian, contextual psychology,
      which grasps the constitutive role of relatedness in the making of all
      experience.

PMID- 10928240
TI  - Will reason prevail? From classic psychoanalysis to new age therapy.

PMID- 10928241
TI  - Buried but not dead: resuscitating psychoanalysis in the twenty-first century.
AB  - This paper argues that psychoanalysis is not dead, but in the process of being
      revived in a more cogent and less erroneous form so it may thrive in the
      twentieth century. The weak adaptive position is seen as the key error in
      mainstream psychoanalytic theory. Erroneous concepts, like the primacy of inner
      fantasies and memories in emotional life and the role of so-called transferences
      in psychotherapy, have been derived from this base. Affording current
      psychoanalytic thinking a strong adaptive position that sees coping with
      environmental impingements as the primary task of the human emotion-processing
      mind sets straight many existing misconceptions. Revising psychoanalysis in light
      of a strong adaptive position brings it into line with the theory of evolution,
      the basic theory of biology. It also clarifies the nature of dreams and leads to
      the creation of a quantitative, mathematically based, formal science of
      psychoanalysis replete with laws and regularities. Also explored is the neglect
      of the emotion-processing mind and efforts to overshadow mental concepts with
      ideas about the brain from neuroscience. The dangers of this loss of mind are
      reviewed. The paper concludes with a discussion of the role played by existential
      death anxiety in the perpetuation of the errors rife in classical psychoanalytic
      thinking. Lessening our use of denial mechanisms in response to death anxieties
      is a key requisite for advancing psychodynamic theories in the next one hundred
      years.

PMID- 10928242
TI  - The transference in psychotherapy: the old vs. the new, analytic vs. dynamic.
AB  - This article takes a look at the concept of transference from several
      contemporary perspectives. It compares the traditional (or classical) view of
      transference with a more contemporary view based on the joint creation of the
      transference. It then discusses the relevance of transference to the dynamically
      based psychotherapies. From this perspective analytically oriented psychotherapy
      is contrasted to dynamically oriented psychotherapy.

PMID- 10928243
TI  - Great expectations: mistaken beliefs of beginning psychodynamic psychotherapists.
AB  - Beginning psychotherapists often have mistaken assumptions about what it is that
      constitutes good psychotherapy and a good psychotherapist. These mistaken beliefs
      are counterproductive and may inhibit the development of appropriate
      psychotherapeutic skills as well as delay, or even prevent, the acquisition of an
      appropriate identity as a psychotherapist. This paper explores six common
      mistaken beliefs on the part of neophyte psychotherapists, providing a basis for
      exploration and discussion of key developmental issues in the genesis of a
      competent psychotherapist.

PMID- 10928245
TI  - Charismatic leadership, boundary issues, and collusion.
AB  - The authors suggest that a charismatic leadership style has an impact on the
      maintenance of boundaries and standards of practice within a department of
      psychiatry. They also underline the need for all members of a self-regulated
      professional group to assume responsibility for the maintenance of standards
      within the group. An overview of leadership tasks and styles, with particular
      emphasis on the qualities of charismatic leadership, is provided, and the impacts
      of boundary violations committed by members of a psychiatric department or
      institute on the integrity of the professional group are also elaborated. The
      authors then develop several hypotheses regarding the phenomenon of emotional
      collusion that occurs in departments in which a charismatic leader becomes
      sexually involved with patients. The individual internal psychological mechanisms
      and companion group dynamics that may allow the leader to be supported at the
      cost of ethical standards, principles of practice, and the ultimate creativity
      and viability of the group are then discussed. The authors conclude that the
      maintenance of standards within a self-regulating professional group must be the
      shared responsibility of all members. The example of boundary violations by a
      charismatic leader is used to illustrate the need for open debate regarding
      fundamental principles required to maintain a healthy functioning of critical
      checks and balances within the psychiatric profession.

PMID- 10928244
TI  - The value of a psychodynamic approach in the managed care setting.
AB  - The managed care setting presents significant challenges to all psychotherapists.
      Psychodynamic therapists, however, experience specific difficulties in this
      environment. Despite managed care's general hostility toward psychodynamic theory
      and practice, psychodynamic therapists provide unique and significant
      opportunities for patients. Psychodynamic training, with its emphasis on careful
      evaluation, exploration of unconscious conflict, transference and
      countertransference, and other therapeutic phenomena, enables clinicians to
      provide an invaluable service to managed care organizations. The case of K., a 45
      year-old man, is used to illustrate the ways in which psychodynamic elements of a
      brief treatment contributed to a successful outcome. The importance of including
      psychodynamic treatment in managed care settings is discussed.

PMID- 10928246
TI  - Psychotherapy of panic syndrome: focusing on ecological aspects of relationships.
AB  - Cognitive Behavioral Therapy (CBT) has been shown to be an effective symptomatic
      treatment for panic attacks; however, this paper recommends complementing it with
      an approach based on an interactive ecological model. The approach is based on
      the thesis that a panic syndrome can occur if patients block an impending and/or
      already initiated development of their relationships, especially involving
      partners or work. The case may be that, over a period of years, phobic attitudes
      and behavior described further in the text have enabled patients to maintain a
      socially positive shaping of their personal niches. Later, phobic avoidance
      behavior is no longer adequate due to the requirements of the new stage of life.
      Unconsciously, patients configure an outer relationship situation that demands of
      them the realization of the impending step in development. Therapy should utilize
      this relationship configuration.

PMID- 10928247
TI  - Conflict in group therapy of chronic schizophrenics: coping with aggression.

PMID- 10928248
TI  - Cognitive behavioral therapy of depression: theory, treatment, and empirical
      status.

PMID- 10928249
TI  - Discussion of boundary issues in psychotherapy.

PMID- 10928250
TI  - [Central and peripheral anesthesia--reevaluation and differentiation].

PMID- 10928251
TI  - [Indications for central versus peripheral regional anesthesia].
AB  - Serious neurological complications caused by spinal hematoma or abscess following
      central neuraxial block have been reported more often during the last years. In
      contrast, severe complications are extremely rare associated with peripheral
      nerve blocks. Concerned about the safety of spinal and epidural anesthesia, we
      encourage the use of peripheral regional techniques for procedures on the lower
      extremity and especially for postoperative regional analgesia. Motor block due to
      lumbar epidural anaesthesia using high concentrations of local anesthetic makes
      spinal hematoma or abscess difficult to recognize. Therefore, low concentrations
      of local anesthetic should be used for postoperative epidural analgesia. Any
      increase in motor block following neuraxial blockade should raise the suspicion
      of a spinal compression (e.g. hematoma or abscess). Other symptoms are back pain,
      radicular pain or paresthesia and incontinence. Disastrous neurological injuries
      can only be prevented by immediate diagnosis (MR, CT or myelography) and therapy
      (surgical decompression).

PMID- 10928252
TI  - [Mechanical autotransfusion procedures. The effect cytokines and leukocytes on
      washed erythrocyte concentrate].
AB  - BACKGROUND: The use of mechanical autotransfusion devices has been sporadically
      associated with adverse effects including pulmonary dysfunction and systemic
      inflammatory response. Stimulated immune cells and proinflammatory cytokines are
      suspected mediators of these complications. This study was designed to evaluate
      whether mechanical autotransfusion stimulates immune cells in wound blood thus
      leading to an increase in cytokines. METHODS: The wound blood of 100 patients
      undergoing total knee arthroplasty was collected and processed using four
      different devices in a randomized order. Leucocyte and cytokine concentrations
      (TNF-alpha, IL-6, IL-10) were determined in the collected wound blood and in the
      washed erythrocyte concentrate. RESULTS: IL-6 concentrations in the collected
      wound blood were markedly higher. TNF-alpha and IL-10 could also be detected at
      lower concentrations. Cell washing reduced IL-6 and IL-10 levels efficiently,
      while TNF-alpha concentrations were significantly increased. Leucocyte
      concentrations were decreased only slightly. A content of 1.0 x 10(9) leucocytes
      remained in the processed blood. CONCLUSION: High concentrations of IL-6 in the
      collected wound blood are reduced extensively by all mechanical autotransfusion
      devices investigated. However, a large amount of leucocytes remains in the
      processed blood. Considering the increase in TNF-alpha concentration after the
      washing, an elevated activity of mononuclear cells in the blood product must be
      assumed.

PMID- 10928253
TI  - [Orthostasis in halothane anesthesia. A model situation for studying
      cerebrovascular autoregulation in infants].
AB  - Halothane causes impairment of cerebrovascular reactivity and autoregulation. We
      used transcranial Doppler sonography (TCD) to investigate the reaction patterns
      of cerebral blood flow velocities (CBFV) during a standardized orthostatic
      maneuver after premedication and during halothane anesthesia in infants. After
      premedication orthostasis led to no significant changes in CBFV. During halothane
      anesthesia CBFV was significantly higher than after premedication, and
      orthostasis induced a significant decrease in CBFV compared to values obtained in
      horizontal position. Heart rate and mean blood pressure were significantly lower
      than before medication during halothane anesthesia. The observed changes in CBFV
      during halothane anesthesia represent a characteristic pattern of impaired
      cerebral autoregulation. The changes in CBFV and heart rate demonstrate that
      neither systemic nor cerebral hemodynamics compensate for hydrostatic inducement
      during halothane anesthesia. The tilting test is a useful tool for determining
      cerebral autoregulation capacity in infants.

PMID- 10928254
TI  - [Hemodynamic effects of spinal anesthesia with 2% lidocaine in comparison to 0.5%
      isobaric bupivacaine].
AB  - BACKGROUND: Our study compared the haemodynamic changes after spinal anesthesia
      with 2% lignocaine and 0.5% plain bupivacaine. METHODS: A controlled, randomized
      trial was performed on 30 patients scheduled for arthroscopic knee surgery. 2%
      lignocaine and 0.5% plain bupivacaine were used for spinal anaesthesia. We
      measured cardiac output (electrical bioimpedance cardiography), blood pressure
      and development of sensory blockade before and for 25 minutes after spinal
      anaesthesia. RESULTS: In patients developing a sensory block below T6 there were
      no differences between both anaesthetics in haemodynamic parameters. But in
      patients developing a sensory block at or above T6 there was a greater drop in
      mean arterial pressure and cardiac output and a faster decrease in heart rate for
      bupivacaine compared to patients receiving Lignocaine. CONCLUSION: In patients
      developing a sensory block at or above the T6 dermatome, the decrease in cardiac
      output and mean arterial pressure in the first 25 min after spinal anaesthesia is
      smaller when 2% lignocaine rather than 0.5% bupivacaine is used for blockade.

PMID- 10928255
TI  - [Remifentanil-propofol for bronchoscopic fiber optic intubation under
      capnographic control].
AB  - We report a case of a 41-years-old woman presenting for revision of a secondary
      reconstructive procedure using the modified Tagliacozzi upper arm flap after
      subtotal maxillectomy. Because of the pedicle flap the upper arm was fixed in a
      pre-facial position and so fiberoptic intubation was required. After routine pre
      anesthetic preparations and topical anesthesia of the nares and nasopharynx a CO2
      measuring catheter as well as a O2 catheter to administer 100% oxygen was
      inserted deeply into the left naris. At that time, a continuous infusion of 0.05
      microgram/kg/min remifentanil and 2 mg/kg/h propofol was started. After 4 min,
      fiberoptic intubation was performed through the right nare without any technical
      difficulties in conscious sedation of the patient. During the entire fiberoptic
      intubation SaO2 was constant at 100% and capnogram tracings with etCO2 values
      ranging from 31 to 33 mmHg were displayed on the monitor. At the end of this
      second surgical procedure with fixed pre-facial upper arm position the patient
      was uneventfully extubated fully awake. For the time period of fiberoptic
      intubation the patient had complete amnesia. CONCLUSION: With the use of nasal
      capnography and capnometry in addition to simultaneous O2 administration during
      fiberoptic intubation under extreme conditions excellent analgosedation with
      propofol and remifentanil could be provided without compromising our patients'
      safety. The presented CO2 measuring and O2 administering device represents a
      simple and cheap expansion of standard anesthetic monitoring during fiberoptic
      intubation.

PMID- 10928256
TI  - [Primary cesarean section. Use of phenylephrine during anesthesia in a patient
      with hypertrophic obstructive cardiomyopathy].
AB  - We report on anaesthesia management for elective Caesarean section in a
      parturient woman with hypertrophic obstructive cardiomyopathy (HOCM). Special
      considerations for anaesthesia are associated with this condition. Women with
      HOCM need a closed diagnostic and therapeutic follow-up during pregnancy.
      Anaesthesiologists have to be aware of the cardiac peculiarities. Special risks
      may arise from endogenous catecholamine release during labour or from therapy
      with beta-adrenergic drugs for treatment of blood pressure drops or suppression
      of uterine contractions. Epidural anaesthesia is an appropriate anaesthesia
      method for Caesarean section, also in patients with HOCM. Adequate hemodynamic
      monitoring is essential. Phenylephrine is a pure alpha-adrenergic vasoconstrictor
      without inotropic effects. It is suitable for therapy of blood pressure drops
      induced by peripheral vasodilation.

PMID- 10928257
TI  - [The menstruation cycle in the postoperative phase. Its effect of the incidence
      of nausea and vomiting].
AB  - OBJECTIVE: Several studies suggest that the menstrual cycle has an impact on
      postoperative nausea and vomiting (PONV). However, many studies report
      inconsistent results. Thus, in this systematic review the results of all
      available studies are compared and statistically synthesised. MATERIALS AND
      METHODS: A systematic search of the literature was performed (Medline, the
      Cochrane-Library, reference lists of matching articles). The main end point in
      each study was defined as occurrence of PONV during an observation interval of at
      least 12 h postoperatively. These data were extracted from each article and the
      pooled incidences of PONV for each day of the menstrual cycle were calculated.
      These incidences were analysed using the chi 2-test. Furthermore the pooled
      incidences of PONV during the following phases of the menstrual cycle were
      calculated: days 1-7, 8-12, 13-15, 16-24, and 25-end of cycle. RESULTS: A total
      of 12 studies with 2625 patients containing informations on the incidence of PONV
      on different days or phases of the menstrual cycle were analysed. The total
      incidence of PONV was 37.3%. The incidence of PONV was lowest (26.9%) on day 20
      and reached its maximum on day 5 (45.0%) with no statistically significant
      differences concerning the incidences of PONV between the different days (p =
      0.75). Furthermore there were no clinically relevant differences in the
      incidences of PONV during the phases of the menstrual cycle: day 1-7: 40.4%; day
      8-12: 32.9%; day 13-15: 38.1%; day 16-24: 34.5%; day 25-end of cycle: 41.5%.
      Prophylactic administration of an antiemetic in some of the studies had no impact
      on these results. CONCLUSION: Studies investigating the influence of the
      menstrual cycle on the incidence of PONV show inconsistent results. Summarising
      the data of these studies suggests that the phase of the menstrual cycle has no
      impact on the occurrence of PONV.

PMID- 10928258
TI  - [The historical development of intensive care medicine in Germany. Contemporary
      considerations. 16. The history of development of therapeutic and diagnostic
      methods in pediatric].

PMID- 10928259
TI  - [Excitation following sevoflurane: a problem in pediatric anesthesia? Comment on
      a paper in Der Anaesthesist (1999)48: 917-918].

PMID- 10928260
TI  - [Excitation following sevoflurane: a problem in pediatric anesthesia? Comment on
      a paper in Der Anaesthesist (1999)48: 917-918].

PMID- 10928261
TI  - [Phytotherapeutics].

PMID- 10928262
TI  - [Anesthesia and perioperative complications].

PMID- 10928263
TI  - [Hypotensive circulatory reactions following cataract operations].

PMID- 10928264
TI  - [Continuing education on a high level. Seminar congress on anesthesiology. Bad
      Gastein. March 12-17, 2000].

PMID- 10928265
TI  - [Cardioprotection in the perioperative phase in non-cardiac procedures].

PMID- 10928266
TI  - An ever-expanding story of cyst formation.
AB  - Autosomal-dominant polycystic kidney disease represents one of the most common
      monogenetic human disorders. The cloning of the PKD1 and PKD2 genes, which are
      mutated in far more than 90% of the patients affected by this disease, has
      generated high hopes for a quick understanding of the pathogenesis of cyst
      formation. However, these expectations have not yet been fulfilled, since the
      function of both polycystin-1 and polycystin-2, the two proteins encoded by PKD1
      and PKD2, still remains a puzzle. In this review, we will highlight some of the
      characteristics of polycystic kidney disease, briefly touch on polycystin-1, and
      then go on to describe recent results of experiments with polycystin-2, since the
      latter is the major focus of our work. We will discuss new evidence which
      suggests that autosomal-dominant polycystic kidney disease actually behaves
      recessively on a cellular level. Finally, a model will be presented that tries to
      explain the available data.

PMID- 10928267
TI  - Tumor necrosis factor alpha and interleukin-1 alpha inhibit through different
      pathways interferon-gamma-induced antigen presentation, processing and MHC class
      II surface expression on astrocytes, but not on microglia.
AB  - Astrocytes and microglia, two glial cell populations of the CNS, have been
      described to be involved in many immune processes. We used defined combinations
      of cytokines, interferon gamma (IFN-gamma)/interleukin-1 alpha (IL-1 alpha) and
      IFN-gamma/tumor necrosis factor alpha (TNF alpha), to simulate different in vitro
      immune environments observed in disease or inflammation. In these conditions, we
      analyzed and compared the regulating effects of these cytokines on cell surface
      and total expression of MHC II and on the capacity of murine astrocytes and
      microglia to present peptide and native antigens to specific primed T cells.
      Neither IL-1 alpha nor TNF alpha affected the IFN-gamma-induced antigen
      presentation capacity of microglia. Astrocytes, however, were severely impaired
      in their capacity to present native antigens and, to a minor extent, a peptide
      antigen. Total expression of MHC II was not affected by these cytokines in
      microglia, whereas in astrocytes it was reduced by IL-1 alpha and increased by
      TNF alpha. Both cytokines downregulated MHC II expression at the surface of
      astrocytes, but not of microglia. This shows that TNF alpha affects the of IFN
      gamma-immunocompetent astrocytes to process and present antigen, probably either
      by altering membrane traffic of MHC II and of antigen and/or enzymatic activities
      associated with these mechanisms, while IL-1 alpha does so by downregulating MHC
      II expression. Altogether, our results illustrate how differently astrocytes and
      microglia react toward a defined, similar immune environment. One type of cell,
      the astrocytes, downregulate their T-cell stimulation and MHC II trafficking, and
      probably also their antigen processing, functions while the other, the microglia,
      maintain their antigen presentation potential.

PMID- 10928268
TI  - Shapes and projections of tertiary plexus neurons of the guinea-pig small
      intestine.
AB  - The axons of neurons that innervate the longitudinal muscle of the small
      intestine in small mammals such as rabbit, rat, guinea pig and mouse form a
      network, the tertiary plexus, against the inner surface of the muscle. In
      general, because of their substantial overlap, it has not been possible to follow
      the ramifications of individual axons in the tertiary plexus. In the present
      work, the longitudinal muscle motor neurons were filled with marker dyes through
      an intracellular microelectrode, and their morphologies and projections were
      examined in whole-mount preparations of longitudinal muscle and myenteric plexus.
      Most neurons that were examined were in the small intestine (ileum and duodenum),
      but a few were examined in the distal colon. Neurons in all regions had similar
      morphologies and projections. The cell bodies were amongst the smallest in
      myenteric ganglia, with major and minor axes of 14 microns and 25 microns (mean,
      n = 40) in the plane of the myenteric plexus. Each neuron had a single axon that
      branched extensively in the tertiary plexus, most had multiple lamellar dendrites
      and a few had filamentous dendrites or a mixture of filamentous and lamellar
      dendrites. The mean area of muscle covered by an axon and its branches extended
      1.6 mm orally to anally and 1.7 mm circumferentially. The area covered was 2.8 +/
      1.9 mm2 (mean +/- SD, n = 23). From the density of occurrence of cell bodies, it
      can be calculated that each point in the longitudinal muscle is innervated by the
      processes of about 100 motor neurons and is influenced by electrotonic conduction
      of signals through the muscle by about 300 motor neurons.

PMID- 10928269
TI  - Immunohistochemical localization of muscarinic receptors (M2) in the rat skin.
AB  - Acetylcholine (ACh) produces pain when applied to human skin and excites
      cutaneous mechanoreceptors and nerve terminals. These effects are partially
      mediated by activation of muscarinic receptors. The expression of muscarinic
      receptor subtype M2 has been shown in sensory neurons of rat dorsal root ganglia
      using reverse transcriptase polymerase chain reaction (RT-PCR), in situ
      hybridization and immunohistochemistry. The purpose of the present study was to
      determine whether these M2 receptors are targeted to the peripheral endings of
      sensory neurons in the rat skin. Double-staining histochemical procedures were
      employed using a specific antiserum to M2 receptors combined with either of the
      following neuronal markers: an antiserum to the neuropeptide substance P, an
      antiserum to the protein gene product 9.5, which is a marker for peripheral nerve
      fibres, and the histochemical marker of a subpopulation of unmyelinated C-fibre
      afferents, I-B4, the Bandeira simplicifolia-derived isolectin. The M2 receptor
      subtype was found on different populations of nerve fibres. In the nerve plexus
      at the epidermal-dermal junction, M2 receptors are mainly present on I-B4
      positive axons but are absent on fibres with substance P immunoreactivity. Sweat
      glands receive M2-receptor-immunoreactive fibres that express neither I-B4
      binding nor substance P immunoreactivity, whereas blood vessels of the deeper
      dermis are innervated by I-B4-positive nerve fibres that are immunoreactive for
      M2 receptors and substance P. In addition to axon profiles, keratinocytes and
      endothelial cells also exhibit M2 receptor immunoreactivity. The results show the
      presence of M2 receptors in neuronal and non-neuronal cells, suggesting multiple
      effects of acetylcholine in the skin.

PMID- 10928270
TI  - Uptake and degradation of radioactively labelled albumin microspheres as markers
      for Kupffer cell phagocytosis.
AB  - Rats were injected with liposomes containing iodixanol (CTP10 Injection; 100 mg
      iodine per kg body weight) followed by a second injection of 125I-tyramine
      cellobiose-albumin microspheres. The amounts of phagocytosed and degraded
      labelled albumin in liver were measured. A reduced uptake and degradation of
      albumin microspheres was observed when the labelled microspheres were injected 2
      h or 24 h after the liposomes compared with that obtained in control animals
      receiving saline. No effect on the uptake and degradation of labelled
      microspheres was observed when the time lag between the injection of liposomes
      and labelled microspheres was 1 week. The data show that the uptake and
      degradation of 125I-tyramine-cellobiose-albumin microspheres can be used as
      indicators of Kupffer cell phagocytotic function following drug uptake by these
      cells.

PMID- 10928271
TI  - Tyrosine phosphorylation: a critical component in the formation of
      hemidesmosomes.
AB  - Our goal was to evaluate the role of tyrosine phosphorylation in the complete
      formation of hemidesmosomes that occurs during development or during remodeling
      after injury. A corneal organ culture system was used to study hemidesmosome
      formation as it would occur in an intact tissue. Phosphorylation of the integrin
      subunit beta 4 and bullous pemphigoid antigen-1 (BPAG-1) was examined, as these
      proteins are known to play a role in linking the electron-dense plaques along the
      basal surface with the intermediate filaments to complete the formation of
      hemidesmosomes. Corneal epithelial sheets were placed on substrata that contained
      an intact basal lamina or basal laminae that had been either modified or removed.
      These constructs were incubated for up to 18 h, and hemidesmosome formation was
      evaluated by using transmission electron microscopy. When epithelial sheets were
      placed on intact basal laminae and incubated in the presence of the tyrosine
      kinase inhibitor genistein (200 microM), hemidesmosome formation was impaired.
      The formation of electron-dense regions was delayed, and no association of
      intermediate filaments was detected. Results were confirmed by biochemical
      studies. When the epithelium and underlying proteins were extracted and
      immunoprecipitated with beta 4 or BPAG-1, tyrosine phosphorylation decreased in
      the presence of genistein. In addition, the phosphorylation of beta 4 decreased
      when epithelial sheets were incubated on substrata from which the basal lamina
      had been removed or altered. Thus, a reduction in phosphorylation of tyrosine
      residues impairs the formation of mature hemidesmosomes, and substrata that fail
      to support hemidesmosome formation also demonstrate decreased phosphorylation of
      tyrosine residues.

PMID- 10928272
TI  - Changes in immunoreactivity to anti-cGnRH-I and -II are associated with
      photostimulated sexual status in male quail.
AB  - In sexually active males exposed to long-day (LD) photoperiod, perikarya in the
      olfactory bulb, lobus parolfactorius, n. accumbens, and preoptic region were
      immunoreactive (ir) to an antiserum against gonadotropin-releasing hormone (anti
      cGnRH-I), and a cluster of ir-perikarya was found in the caudal-most septal area.
      Ir-perikarya in these brain areas of sexually inactive short-day (SD) males were
      located within more discrete areas than those in LD brain, which were more
      scattered in appearance. Absolute cell numbers were similar between LD and SD
      brains. Ir-fibers in LD brains were mostly in the external median eminence, along
      the lateral ventricle to septum (especially in and about the n. accumbens), in
      the septal-preoptic area, along the third ventricle, and at the n. commissure
      palli. There were fewer ir-fibers in SD brain. Many small dark ring-like ir
      structures were found in the hyperstriatum, hippocampus, and n. taeniae.
      Interpreted as being ir-terminals on non-ir perikarya, these were not observed in
      SD males. cGnRH-II ir-perikarya were observed in only two areas regardless of
      reproductive status: (1) ventral to the substantia grisea centralis and caudal to
      the oculomotor complex, and (2) scattered in and about the lateral hypothalamus.
      Ir-fibers occurred in the habenular area, hyperstriatum, hippocampus,
      parahippocampal area, cortex piriformis, and n. taeniae. cGnRH-II ir-fibers
      occurred in the external median eminence but were less intensely stained than
      cGnRH-I ir-fibers. These fibers in SD males were similar except in the
      diencephalon, where scattered swellings were observed. Thus, the appearance and
      distribution of anti-cGnRH-I and -II ir-structures change with the sexual status
      of male quail, but changes in immunoreactivity to anti-cGnRH-I appear to be more
      widespread.

PMID- 10928273
TI  - Identification of Reissner's fiber-like glycoproteins in two species of
      freshwater planarians (Tricladida), by use of specific polyclonal and monoclonal
      antibodies.
AB  - By using one polyclonal antiserum raised against bovine Reissner's fiber and
      seven monoclonal antibodies raised against bovine Reissner's fiber and against
      immunopurified bovine subcommissural organ glycoproteins, we have investigated
      two freshwater planarian species (Girardia tigrina, Schmidtea mediterranea) by
      light- and electron-microscopic immunocytochemistry. ELISA probes showed that the
      monoclonal antibodies recognized different, nonoverlapping, unrepeated,
      proteinaceous epitopes present in the same compounds of bovine Reissner's fiber.
      Cells immunoreactive to the polyclonal and monoclonal antibodies were found in
      the dorsal and ventral integument of both planarian species. Labeled cuboid
      epidermal cells bore cilia and displayed several types of secretory granules;
      they were covered by a film of immunoreactive material. Studies on adjacent thin
      and semithin sections revealed coexistence of label in the same regions and in
      the same cells when two different monoclonal antibodies were used. These results
      indicate that a secretory substance immunologically similar to the secretion of
      the vertebrate subcommissural organ is present in primitive tripoblasts such as
      planarians, suggesting that these secretions are ancient and well conserved in
      phylogeny.

PMID- 10928274
TI  - Structure and proteoglycan composition of specialized regions of the elastic
      tendon of the chicken wing.
AB  - The elastic tendon of the avian wing has been described by others as a unique
      structure with elastic properties due to the predominance of elastic fibers in
      the midsubstance. Further analyses of the tendon have shown it to possess five
      anatomically distinct regions. Besides the major elastic region, a distally
      located fibrocartilage and three tendinous regions are present. The tendinous
      regions connect: (1) the muscle to the elastic region, (2) the elastic region to
      the fibrocartilage and (3) the latter to the insertion site. The elastic region
      possesses thick and abundant elastic fibers and very thin, interconnecting
      collagen fibers. The collagen fibers in the sesamoid fibrocartilage are thick and
      interwoven, defining spaces occupied by fibrochondrocytes embedded in a non
      fibrillar and highly metachromatic matrix. Biochemical analyses have shown that
      the fibrocartilage has about tenfold the amount of glycosaminoglycans (GAGs)
      found in the other regions. The main GAG in this region was chondroitin sulfate
      (CS) (plus keratan sulfate as detected immunocytochemically), while the other
      regions showed variable amounts of CS, dermatan sulfate (DS) and heparan sulfate.
      Further analyses have shown that a large CS-bearing proteoglycan is found in the
      fibrocartilage. The elastic region possesses two main proteoglycans, a large CS
      bearing proteoglycan (which reacted with an antibody against keratan sulfate
      after chondroitinase ABC treatment) and a predominant DS-bearing proteoglycan,
      which showed immunoreactivity when assayed with an anti-biglycan antibody. The
      results demonstrate that the elastic tendon is a complex structure with complex
      regional structural and compositional adaptations, suited to different
      biomechanical roles.

PMID- 10928275
TI  - Differential expression of dystrophin, utrophin, and dystrophin-associated
      proteins in human muscle culture.
AB  - The dystrophin-associated protein complex (DAP) plays an important role in
      sarcolemmal function. Mutations of DAP elements lead to diverse forms of muscular
      dystrophies, among them Duchenne muscular dystrophy, one of the most severe
      neuromuscular diseases. Strategies in gene therapy are being assessed to restore
      DAP stability. However, the relationship between DAP elements and time-course of
      the DAP formation are still not known in detail. In order to better understand
      the relationship among DAP proteins, we therefore studied their expression during
      development in human muscle culture in comparison with developmentally regulated
      muscle proteins. Desmin immunoreactivity (IR) was detected by 3 days in vitro
      (DIV3), IR for developmental heavy-chain myosin, vimentin, utrophin, and beta
      dystroglycan, as well as alpha-, beta-, and gamma-sarcoglycan, a day later. delta
      Sarcoglycan was found by DIV7; dystrophin could be detected only by DIV11. In
      general, DAP proteins were first located in the perinuclear region, later
      diffusely in the cytoplasm, and finally exclusively at the membrane. This
      sequence of events during muscle development gives further support to our
      suggestion that utrophin could be a precursor of dystrophin during development
      and regeneration. These data also suggest that utrophin alone is sufficient to
      anchor the complex, which is important when utrophin replacement strategies are
      being investigated for the treatment of dystrophinopathies. In this study we
      demonstrated the establishment of a culture technique that should allow the close
      study of DAP expression in diseased muscle, including its use after gene
      modulatory strategies.

PMID- 10928276
TI  - Distribution of growth-blocking peptide in the insect central nervous tissue.
AB  - Parasitization of the armyworm Pseudaletia separata by the endoparasitic wasp
      Cotesia kariyai inhibits larval growth and delays pupation, conditions necessary
      for proper maturation of the parasite larvae. Parasitization is correlated with
      an elevated level of a 25-amino-acid hormone-like peptide, growth-blocking
      peptide (GBP, ENFSGGCVAGYMRTPDGRCKPTFYQ). Injection of synthetic GBP into
      nonparasitized larvae dose dependently mimics the effects of parasitization by
      delaying the larval development. Here we studied the relationship between
      parasitization and both the production and distribution of GBP in central nervous
      tissues. We found that parasitization is correlated with an elevated expression
      of GBP mRNA, and increased concentrations of both proGBP and GBP in the host
      insect brain and subesophageal ganglion. The increase in proGBP precedes that of
      the mature GBP by about 12 h. In situ hybridization analysis using sections of
      parasitized and nonparasitized larval brains showed strong expression of GBP mRNA
      in perineural cells and/or class I neuroglia in the rind of both larval brains.
      The expression in parasitized larval brain-subesophageal ganglion is
      approximately two- to threefold higher than that in nonparasitized larvae. The
      presence of GBP in insect neural tissue, and its role in inhibiting growth,
      suggest an involvement in the regulation of neurosecretory cells.

PMID- 10928277
TI  - The morphology of apoptosis.
AB  - The concept of apoptotic cell death as an essential part of the development and
      life of complex organisms has been devised in different situations and tested
      from various angles. This review article discusses the morphological changes
      during death by apoptosis. In cells undergoing apoptosis, an intracellular
      signalling pathway operates cell autonomously to implement the death and disposal
      of the cell. The similarity of the biochemical events during apoptosis in
      different situations is reflected by a high uniformity of morphological changes
      in many situations of naturally occurring or experimentally induced cell death.
      The unifying concept of apoptosis has been derived from the observation of this
      morphological consistency of dying cells almost 30 years ago. Since then, we have
      learned much about the intracellular signalling in the apoptotic process and the
      molecular background has been delineated which guides the initiation of the
      morphological changes. Here, an attempt is made to present the current knowledge
      about the molecular events in the development of these morphological alterations
      and to place these changes in the context of apoptotic cell death.

PMID- 10928278
TI  - Detection of apoptosis in tissue sections.
AB  - During the last few years, detection of apoptosis has evolved from a
      predominantly morphological basis to the use of ever more specific techniques.
      The methods widely used to visualize DNA fragmentation in tissue sections are now
      supplemented by a variety of specific antisera against components of the cell
      death pathways. Essential requirements for apoptosis detection techniques include
      high sensitivity for apoptotic cells, the ability to differentiate between
      apoptotic and necrotic cell death and other forms of DNA damage, and the
      distinction between different stages of the cell death process. In this overview,
      we will focus on recent technical advances in apoptosis detection covering
      improvements of in situ DNA fragmentation techniques, as well as pointing out
      some of the new tools available for the detection of apoptotic cells in tissue.

PMID- 10928279
TI  - Cell volume regulation in immune cell apoptosis.
AB  - The loss of cell volume is an early and fundamental feature of programmed cell
      death or apoptosis; however, the mechanisms responsible for cell shrinkage during
      apoptosis are poorly understood. The loss of cell volume is not a passive
      component of the apoptotic process, and a number of experimental findings from
      different laboratories highlight the importance of this process as an early and
      necessary regulatory event in the signaling of the death cascade. Additionally,
      the loss of intracellular ions, particularly potassium, has been shown to play a
      primary role in cell shrinkage, caspase activation, and nuclease activity during
      apoptosis. Thus, an understanding of the role that ion channels and plasma
      membrane transporters play in cellular signaling during apoptosis may have
      important physiological implications for immune cells, especially lymphocyte
      function. Furthermore, this knowledge may also have an impact on the design of
      therapeutic strategies for a variety of diseases of the immune system in which
      apoptosis plays a central role, such as oncogenic processes or immune system
      disorders. The present review summarizes our appreciation of the mechanisms
      underlying the early loss of cell volume during apoptosis and their association
      with downstream events in lymphocyte apoptosis.

PMID- 10928280
TI  - Apoptosis in cardiac development.
AB  - Cell degeneration, as a phenomenon accompanying developmental processes, was
      originally described over a century ago. Apoptosis, a term introduced
      approximately three decades ago, has occupied investigators particularly with
      respect to cell and tissue kinetics, emphasizing its role in the disposal of
      supernumerary, malinstructed or damaged cells. Although apoptosis is mostly
      related to developmental processes, evidence has been gathered indicating that it
      may also perform other roles. In this review, which concentrates on cardiac
      development, we examine focal apoptosis and subsequent signal cascades in
      combination with timed morphogenetic events. Apoptosis mainly occurs in the non
      myocardial compartment of the embryonic heart, a compartment that consists of
      cells derived from the endocardium, the epicardium and the neural crest. The last
      mentioned population invades the outflow tract and the atrioventricular
      endocardial cushions. The signalling cascade seems to involve the activation of
      latent transforming growth factor beta, resulting in cardiomyocyte migration and
      subsequent myocardialization of the endocardial cushions. Aberrant apoptosis
      accompanies cardiac anomalies. Furthermore, an apoptotic population is found
      surrounding the developing conduction system. A possible role for differentiation
      is suggested.

PMID- 10928281
TI  - Apoptosis in the developing visual system.
AB  - Programmed cellular death is a widespread phenomenon during development of the
      nervous system. Two classes of molecules are particularly important in the
      context of apoptosis control in the nervous system: intracellular effectors
      homologous to the Caenorhabditis elegans Ced-3, -4, and -9 proteins, which in
      mammals correspond to the proteases of the caspase family, Apaf-1, and the
      members of the Bcl-2 protein family, and neurotrophic factors. Retinal ganglion
      cells lend a convenient model system with which to investigate apoptosis in
      central neurons during development as well as after injury. In this review, we
      discuss the role of these molecules in the control of programmed cellular death
      in the retinotectal system. Transgenic animal models and expression studies have
      shown that caspases, Bcl-2, Bax, and possibly Bcl-X are necessary players for the
      control of programmed cellular death in retinal ganglion cells. Bax and caspase 3
      expression in retinal ganglion cells is upregulated after injury, and inhibition
      of Bax or caspase 3 increases the survival of injured retinal ganglion cells.
      Neurotrophins can support the survival of injured retinal ganglion cells, but
      this effect is transient. The physiological role of neurotrophins in the
      development of the retinocollicular system seems more related to the topographic
      refinement of retinocollicular projections, a process that is mediated, at least
      partially, by selective elimination of retinal ganglion cells making
      inappropriate topographic projections.

PMID- 10928282
TI  - Developmental motoneuron cell death and neurotrophic factors.
AB  - During the development of higher vertebrates, motoneurons are generated in
      excess. In the lumbar spinal cord of the developing rat, about 6000 motoneurons
      are present at embryonic day 14. These neurons grow out axons which make contact
      with their target tissue, the skeletal muscle, and about 50% of the motoneurons
      are lost during a critical period from embryonic day 14 until postnatal day 3.
      This process, which is called physiological motoneuron cell death, has been the
      focus of research aiming to identify neurotrophic factors which regulate
      motoneuron survival during this developmental period. Motoneuron cell death can
      also be observed in vitro when the motoneurons are isolated from the embryonic
      avian or rodent spinal cord. These isolated motoneurons and other types of
      primary neurons have been a useful tool for studying basic mechanisms underlying
      neuronal degeneration during development and under pathophysiological conditions
      in neurodegenerative disorders. Accumulating evidence from such studies suggests
      that some specific requirements of motoneurons for survival and proper function
      may change during development. The focus of this review is a synopsis of recent
      data on such specific mechanisms.

PMID- 10928283
TI  - Regulation of activation-induced cell death of mature T-lymphocyte populations.
AB  - Resting mature T lymphocytes are activated when triggered via their antigen
      specific T-cell receptor (TCR) to elicit an appropriate immune response. In
      contrast, preactivated T cells may undergo activation-induced cell death (AICD)
      in response to the same signals. along with cell death induced by growth factor
      deprivation, AICD followed by the elimination of useless or potentially harmful
      cells preserves homeostasis, leads to the termination of cellular immune
      responses and ensures peripheral tolerance. T-cell apoptosis and AICD are
      controlled by survival cytokines such as interleukin-2 (IL-2) and by death
      factors such as tumor necrosis factor (TNF) and CD95 ligand (CD95L). In AICD
      sensitive T cells, stimulation upregulates expression of one or several death
      factors, which in turn engage specific death receptors on the same or a
      neighboring cell. Death receptors are activated by oligomerization to rapidly
      assemble a number of adapter proteins and enzymes to result in an irreversible
      activation of proteases and nucleases that culminates in cell death by apoptosis.
      Increased knowledge of the molecular mechanisms that regulate AICD of lymphocytes
      opens new immunotherapeutic perspectives for the treatment of certain autoimmune
      diseases, and has implications in other areas such as transplantation medicine
      and AIDS research.

PMID- 10928285
TI  - Apoptosis in the aging process.
AB  - Although many hypotheses have been proposed to explain the aging process, the
      exact mechanisms are not well defined. Recent accumulating evidence indicates
      that dysregulation of the apoptotic process may be involved in some aging
      processes; however, it is still debatable how exactly apoptosis is expressed
      during aging in vivo. In this review, we discuss recent findings related to
      apoptosis of individual organs during aging and their significance. We
      demonstrate that aging enhances apoptosis and susceptibility to apoptosis in
      several types of intact cells. In contrast, in certain genetically damaged,
      initiated, and preneoplastic cells, aging suppresses these age-associated
      apoptotic changes. In various cells, apoptosis enhances the elimination of
      damaged and dysfunctional cells presumably caused by oxidative stress, glycation,
      and DNA damage. In these cases, the incidence of apoptosis correlates with the
      level of accumulated injury. It is concluded that apoptosis plays an important
      role in the aging process and tumorigenesis in vivo probably as an inherent
      protective mechanism against age-associated tumorigenesis.

PMID- 10928286
TI  - Radiation-induced apoptosis.
AB  - Radiation-induced apoptosis has been a topic of intense research during the last
      decade. Its recognition as a significant component of radiation-induced cell
      death has initiated several lines of investigation aimed at modulating the
      apoptotic response and thereby radiosensitivity. These strategies require the
      integration of both classical radiobiological concepts and the knowledge of the
      biochemical and molecular biological mechanisms involved in apoptosis induction.
      This review discusses mechanisms of radiation-induced apoptosis and highlights
      the radiobiological and radiotherapeutical relevance of this mode of cell death.

PMID- 10928287
TI  - Apoptosis and cancer chemotherapy.
AB  - Apoptosis is a fundamental mechanism of cell death that can be engaged by a range
      of cellular insults. One of the major modes of action of chemotherapeutic drugs
      may be via the activation of apoptosis. Understanding how the cell death program
      is engaged following an insult, and hence why it fails to be engaged in certain
      settings, offers a novel approach to overcoming the clinical problem of drug
      resistance. The tumour suppressor gene p53 and its downstream effector genes p21,
      mdm-2, and gadd45 seem to be important in the cellular response to genotoxic drug
      induced damage. Considerable evidence has accrued about the effect of mutations
      of this pathway on drug sensitivity and this is discussed. The expanding Bcl-2
      family of proteins also play an important role in the cell death program.
      Evidence suggests that these proteins may function as integrators of damage
      signals, and may be the final decision point as to whether a cell lives or dies.
      These proteins may thus represent a logical target for new approaches to
      overcoming drug resistance.

PMID- 10928288
TI  - Apoptosis in prostate carcinogenesis. A growth regulator and a therapeutic
      target.
AB  - Development of effective therapeutic modalities for the treatment of human cancer
      relies heavily upon understanding the molecular alterations that result in
      initiation and progression of the tumorigenic process. Many of the molecular
      changes identified in human prostate tumorigenesis so far play key roles in
      apoptosis regulation. Apoptosis represents a universal and exquisitely efficient
      cellular suicide pathway. Since the therapeutic goal is to trigger tumor
      selective apoptotic cell death (without clinically significant effects on the
      host), elucidation of the mechanisms underlying apoptosis deregulation will lead
      to the identification of specific cellular components for targeting therapeutic
      interventions. As our understanding of its vital role in the development and
      growth of the prostate gland has expanded, numerous genes that encode apoptotic
      regulators have been identified that are severely impaired in prostate cancer
      cells. In addition, the expression of apoptotic modulators within prostatic
      tumors appears to correlate with tumor sensitivity to traditional therapies such
      as hormonal ablation and radiotherapy. No strict correlation between apoptosis
      induction and a patient's long-term prognosis has emerged, perhaps due to the
      fact that the ability to achieve initial remission alone does not adequately
      predict long-term outcome. This review will encompass the known molecular changes
      intimately involved in the apoptotic pathway which have potential prognostic
      value in disease progression, as well as therapeutic significance in the
      enhancement of the apoptotic response to novel and established treatment
      strategies for the treatment of androgen-dependent and androgen-independent
      prostatic tumors. The main focus will be on the role of the transforming growth
      factor-beta (TGF-beta) signaling pathway, bcl-2 and the bcl-2 family members, the
      caspase cascade (apoptosis executioners), and the Fas pathway in induction and
      regulation of apoptosis following therapeutic stimuli for the management of
      advanced prostate cancer.

PMID- 10928289
TI  - Apoptosis in multiple sclerosis.
AB  - Several recent studies have provided evidence that apoptosis is an important
      feature in the pathogenesis of multiple sclerosis (MS), an autoimmune disease of
      the central nervous system. Apoptosis presumably plays a role in the
      immunoregulation via activation-induced T-cell death (AICD) and in local
      processes of tissue damage. In this review the dual role of apoptosis in the MS
      pathogenesis and its relevance regarding therapeutic concepts is discussed.

PMID- 10928290
TI  - Apoptotic and antiapoptotic mechanisms in stroke.
AB  - Apoptosis is a form of programmed cell death that occurs in neurons during
      development of the nervous system and may also be a prominent form of neuronal
      death in chronic neurodegenerative disorders such as Alzheimer's and Parkinson's
      diseases. Recent findings also implicate apoptosis in neuronal degeneration after
      ischemic brain injury in animal models of stroke. Activation of both apoptotic
      and antiapoptotic signaling cascades occurs in neurons in animal and cell culture
      models of stroke. Apoptotic cascades involve: increased levels of intracellular
      oxyradicals and calcium; induction of expression of proteins such as Par-4
      (prostate apoptosis response-4), which act by promoting mitochondrial dysfunction
      and suppressing antiapoptotic mechanisms; mitochondrial membrane depolarization,
      calcium uptake, and release of factors (e.g., cytochrome c) that ultimately
      induce nuclear DNA condensation and fragmentation; activation of cysteine
      proteases of the caspase family; activation of transcription factors such as AP-1
      that may induce expression of "killer genes." Antiapoptotic signaling pathways
      are activated by neurotrophic factors, certain cytokines, and increases in
      oxidative and metabolic stress. Such protective pathways include: activation of
      the transcription factors (e.g., nuclear factor-kappa B, NF-kappa B) that induce
      expression of stress proteins, antioxidant enzymes, and calcium-regulating
      proteins; phosphorylation-mediated modulation of ion channels and membrane
      transporters; cytoskeletal alterations that modulate calcium homeostasis; and
      modulation of proteins that stabilize mitochondrial function (e.g., Bcl-2).
      Intervention studies in experimental stroke models have identified a battery of
      approaches of potential benefit in reducing neuronal death in stroke patients,
      including administration of antioxidants, calcium-stabilizing agents, caspase
      inhibitors, and agents that activate NF-kappa B. Interestingly, recent studies
      suggest novel dietary approaches (e.g., food restriction and supplementation with
      antioxidants) that may reduce brain damage following stroke.

PMID- 10928291
TI  - Cell death in polyglutamine diseases.
AB  - An increasing number of inherited neurodegenerative diseases are known to be
      caused by trinucleotide repeat expansions in the respective genes. At least nine
      disorders result from a CAG trinucleotide repeat expansion which is translated
      into a polyglutamine stretch in the respective proteins: Huntington's disease
      (HD), dentatorubral pallidolysian atrophy (DRPLA), spinal bulbar muscular atrophy
      (SBMA), and several of the spinocerebellar ataxias (SCA1, 2, 3, 6, 7 and 12).
      Although the molecular steps leading to the specific neuropathology of each
      disease are unknown and are still under intensive investigation, there is
      increasing evidence that some CAG repeat disorders involve the induction of
      apoptotic mechanisms. This review summarizes the clinical and genetic features of
      each CAG repeat disorder and focuses on the common mechanistic steps involved in
      the disease progression of these so-called polyglutamine diseases. Among the
      common molecular features the formation of intranuclear inclusions, the
      recruitment of interacting polyglutamine-containing proteins, the involvement of
      the proteasome and molecular chaperones, and the activation of caspases are
      discussed with regard to their potential implication for the induction of cell
      death.

PMID- 10928292
TI  - Unravelling the links between calcium excretion, salt intake, hypertension,
      kidney stones and bone metabolism.
AB  - Evidence from animal, clinical and epidemiological studies suggests that high
      blood pressure is associated with abnormalities of calcium metabolism, leading to
      increased calcium loss, secondary activation of the parathyroid gland, increased
      movement of calcium from bone and increased risk of urinary tract stones. Some of
      these abnormalities are detectable in children and young people and continue
      throughout adult life. The cluster of abnormalities may be due either to a
      primary renal tubular defect ('renal calcium leak' hypothesis) or to the effect
      of central volume expansion seen in hypertension ('central blood volume'
      hypothesis). A high salt intake is known to aggravate these abnormalities and
      their consequences. If substantial calcium loss related to high blood pressure is
      sustained over many decades, increased excretion of calcium in the urine may
      result in an increased risk of urinary tract stones, and the increased movement
      of calcium from bone may result in higher rates of bone mineral loss, thereby
      increasing the risk of osteoporosis. The present review summarises the evidence,
      suggests a unifying hypothesis and discusses clinical and public health
      implications.

PMID- 10928284
TI  - Hormonal regulation of physiological cell turnover and apoptosis.
AB  - Physiological cell turnover plays an important role in maintaining normal tissue
      function and architecture. This is achieved by the dynamic balance of cellular
      regeneration and elimination, occurring periodically in tissues such as the
      uterus and mammary gland, or at constant rates in tissues such as the
      gastrointestinal tract and adipose tissue. Apoptosis has been identified as the
      prevalent mode of physiological cell loss in most tissues. Cell turnover is
      precisely regulated by the interplay of various endocrine and paracrine factors,
      which modulate tissue and cell-specific responses on proliferation and apoptosis,
      either directly, or by altering expression and function of key cell proliferative
      and/or death genes. Although recent studies have provided significant information
      on specific tissue systems, a clearly defined pathway that mediates cell turnover
      has not yet emerged for any tissue. Several similarities exist among the various
      tissues with regard to the intermediates that regulate tissue homeostatis,
      enabling a better understanding of the general mechanisms involved in the
      process. Here we review the mechanisms by which hormonal and cytokine factors
      mediate cell turnover in various tissues, emphasizing common themes and tissue
      specific differences.

PMID- 10928293
TI  - Renal endothelin-1 is linked to changes in urinary salt and volume in essential
      hypertension. Salt Sensitivity Group of the Italian Society of Hypertension.
AB  - METHODS: We investigated the influence of salt intake on urinary and plasma
      endothelin-1 (ET-1) in 55 patients who entered a two-week double-blind,
      randomised, crossover study comparing a 50 mMol/day salt intake and 150 mMol/day.
      Twenty-four-hour ET-1 excretion and plasma ET-1 were measured by RIA on pre
      extracted samples. RESULTS: In the whole cohort (n=55), changes in urinary ET-1
      were related to salt excretion (r=0.28, P=0.04) and urinary volume (r=0.47,
      P=0.0001). In a multivariable model, changes in PRA, plasma aldosterone, blood
      pressure and heart rate did not add any predictive power to salt excretion with
      regard to urinary ET-1 variations. The relationship between urinary volume and
      urinary ET-1 was stronger than that of urinary sodium with ET-1 excretion because
      sodium was excluded from the multivariable model when urinary volume was
      introduced. Changes in urinary ET-1 were unrelated to mean blood pressure changes
      (P=0.66). Changes in plasma ET-1 were unaffected by changes in salt intake
      (P=0.58) but were strongly related to those in PRA (r= -0.45, P=0.01) and plasma
      aldosterone (r= -0.53, P=0.002). CONCLUSIONS: The renal excretion of ET-1 is
      influenced by changes in salt intake and appears largely independent of the blood
      pressure response to salt. Changes in urinary volume which accompany variations
      in salt excretion play an important role in this response. Since urinary ET-1
      reflects its renal synthesis, our data support the notion that renal ET-1 plays a
      role in the regulation of sodium balance in patients with mild hypertension.

PMID- 10928294
TI  - Cardiac and vascular abnormalities in renal transplant patients: differential
      effects of cyclosporin and azathioprine.
AB  - Renal transplant patients die prematurely of cardiovascular disease and LV
      hypertrophy is now recognised as an important adverse prognostic indicator. This
      study investigated the factors implicated in the development of echocardiographic
      abnormalities (including LV hypertrophy) and the possible differential effects of
      treatment with cyclosporin and azathioprine. A cross-sectional study was
      undertaken in 46 patients randomly assigned to immunosuppressant treatment with
      either cyclosporin or azathioprine at 1 year post-transplantation: patients were
      studied not less than 5 years after assignment to cyclosporin (CyA) - or
      azathioprine (Aza)-based treatment regimens. Although clinic blood pressure
      control was not different in the two treatment groups, 24 hour ambulatory BP
      (ABP), particularly night-time BP, was significantly higher in the CyA group.
      There was a trend for both left ventricular hypertrophy (61 vs. 43%) and carotid
      wall thickening (43 vs. 26%) to be more common in the CyA group though this
      failed to achieve statistical significance. Left ventricular mass was determined
      by ABP, rather than clinic BP, and was also associated with increased QT
      dispersion. Multivariate analysis identified that 24 hour ambulatory systolic
      blood pressure (ASBP) and time on renal replacement therapy (RRT) were the major
      determinants of LV mass. Thus, despite the absence of differences in clinic BP
      measurements, CyA treatment was associated with higher rates of cardiovascular
      functional and structural abnormalities. This small scale study has identified
      cardiovascular functional and structural abnormalities in renal transplant
      patients, particularly in those receiving CyA-based immunosuppressive therapy.
      However, rather than reflecting a direct effect of CyA they are related to
      increased 24 ABP (but not clinic BP). These data suggest that ABP should be used
      to monitor and target antihypertensive therapy in this high risk patient group.
      Moreover, the future use of non-calcineurin inhibitor immunosuppressant therapy
      may have benefits on blood pressure control and LV mass.

PMID- 10928295
TI  - Thoracic aortic dissection in a patient with autosomal dominant polycystic kidney
      disease treated with maintenance hemodialysis.
AB  - A patient with autosomal dominant polycystic kidney disease (ADPKD) on
      maintenance hemodialysis (HD) experienced spreading back pain with a sudden
      onset, and was diagnosed with thoracic aortic dissection. Reports of ADPKD with
      aortic dissection are rare. Hypertension, which is essentially universal both
      among ADPKD and hemodialysis patients, is a known risk factor for aortic
      dissection. Additionally, some reports have indicated that patients with ADPKD
      have aortic fragility. We suspect that aortic dissection may be less rare than
      presently apparent among HD patients with ADPKD.

PMID- 10928296
TI  - Chronobiology of blood pressure.
AB  - The chronobiology of blood pressure is a useful tool for examining serial data to
      quantify the dynamics of variability. The implications and applications for
      diagnosis and therapy are discussed, with clinical examples. The chronobiological
      patterns of hypertension are described. Chronobiology can make a real
      contribution to the prevention of disease. Chronobiology helps diagnose circadian
      hyper-amplitude-tension (CHAT), a condition in which excessive circadian BP
      amplitude precedes chronic established hypertension.

PMID- 10928297
TI  - Endothelial dysfunction in hypertension.
AB  - Endothelium can deeply influence vascular tone and structure. The main
      endothelium derived factor is nitric oxide, which is not only a potent
      vasodilator but also inhibits platelet aggregation, smooth muscle cell migration
      and proliferation, monocyte adhesion and adhesion molecule expression, thus
      protecting the vessel wall against the development of atherosclerosis and
      thrombosis. In human hypertension, endothelial dysfunction has been documented in
      peripheral and coronary macro and microcirculation and in renal circulation.
      Impaired endothelium-dependent vasodilation associated with essential
      hypertension seems to be a primary phenomenon, since it can be detected in the
      offspring of essential hypertensive patients, shows no clear correlation with
      blood pressure value, and is not normalized by the mere reduction of blood
      pressure. The phenomenon responsible for endothelial alteration in essential
      hypertensive patients seems to be the activation of an alternative pathway
      involving cyclooxygenase which reduces NO availability through production of
      oxidative stress. This alteration in the NO pathway could be the main mechanism
      through which a dysfunctional endothelium could be a promoter of atherosclerosis
      and thrombosis in essential hypertension.

PMID- 10928298
TI  - Nitric oxide--angiotensin II axis in renal and cardiovascular injury.
AB  - The knowledge and the information about Renin Angiotensin System and Arginine
      Nitric Oxide pathway helped us in understanding more about cardiac, vascular and
      renal systems, their function, the physiology, and pathophysiology of different
      diseases that may affect them. The existence of a Nitric Oxide/Angiotensin II
      axis, brought modification to our ways of thinking with new and more
      pathophysiological approaches to the treatment of hypertension and end-organ
      disease. There appears to be a link between hypertension, salt sensitivity,
      endothelial function and NO-AnglI axis on one side and end organ damage on the
      other side. Anti-hypertensive agents that can restore endothelial function beside
      their antihypertensive effect, may be better in preventing or at least slowing
      end-organ damage.

PMID- 10928299
TI  - The kidney and the neurogenic control of blood pressure in renal disease.
AB  - Hypertension is very common in patients with chronic renal failure (CRF) and it
      contributes to morbidity and mortality as well as to the progression of renal
      disease. Several mechanisms may play a role in the pathogenesis of hypertension
      in CRF, but the best known are sodium retention and activation of the renin
      angiotensin-aldosterone system. More recently, evidence has accumulated to
      support a role for increased sympathetic nervous system (SNS) activity in the
      genesis of hypertension associated with CRF. Our laboratory findings indicate
      that specific renal injuries, caused by 5/6 nephrectomy and/or phenol injection
      in the kidney, activate renal afferent pathways that connect with integrative
      structures in the brain involved in the regulation of SNS activity and blood
      pressure. This results in a rise in blood pressure sustained by noradrenergic
      mechanisms. Our laboratory has also shown that the rise in central SNS activity
      is mitigated by increased local expression of nitric oxide synthase (NOS)-mRNA
      and nitric oxide (NO) production, and by upregulation of interleukin-1beta.

PMID- 10928300
TI  - Hypertension and progression of renal disease.
AB  - That systemic hypertension is involved in the progression of human renal disease
      is mostly suggested by the way anti-hypertensive treatment affects the course of
      the disease. Clinical evidence has been obtained from observational studies as
      well as from studies of dietary protein restriction. In addition, several trials
      have compared the effects of different antihypertensive agents. The angiotensin
      converting-enzyme inhibitors have the best renoprotective effect when compared to
      conventional agents and calcium channel blockers. In most studies, ACE-inhibitors
      approximately halved the risk of progressive renal functional deterioration in
      patients with non-diabetic nephropathies; this protection was associated with a
      significant reduction in systemic blood pressure and proteinuria. Statistical
      analysis, however, also suggests a direct effect of ACE-inhibitors on the kidney.

PMID- 10928301
TI  - How much must blood pressure be reduced in order to obtain the remission of
      chronic renal disease?
AB  - Most chronic nephropathies are characterized by a progressive decline in
      glomerular filtration rate (GFR) that may lead to renal function replacement by
      dialysis or transplant. Hypertension has an extremely important role among the
      various mechanisms contributing to renal function deterioration. High blood
      pressure levels are associated with increased urinary excretion of proteins and
      the decrease of systemic and glomerular hypertension reduces urinary excretion of
      proteins and preserves renal function deterioration. Moreover, recent studies
      found that an intensified blood pressure control (less than 130/80 mmHg) can slow
      the progression of diabetic and non diabetic renal disease even more than
      conventional blood pressure control. The Ramipril Efficacy in Nephropathy (REIN)
      Study showed that ramipril, an ACE-inhibitor, slowed the rate of GFR decline and
      halved the combined risk of doubling serum creatinine or end stage renal failure
      (ESRF) in patients with nephrotic range proteinuria as compared to conventional
      antihypertensive therapy, at comparable levels of blood pressure control. In
      these patients, prolonged enough treatment (at least 36 months) with ramipril,
      lowered the velocity of GFR decline and reduced the risk of dialysis. Thus, both
      tight blood pressure control and ACE-inhibitors may have a renoprotective effect.
      It will be interesting to evaluate whether the two combined approaches may have
      sinergistic effects.

PMID- 10928302
TI  - Effects of antihypertensive treatment on endpoints in the diabetic patients
      randomized in the Systolic Hypertension in Europe (Syst-Eur) trial.
AB  - In this review we attempt to determine the role of calcium channel blockers in
      preventing cardiovascular sequela in patients with both hypertension and diabetes
      mellitus. The data have been collected from three sources: post hoc analyses of
      subgroups of diabetic patients in placebo-controlled hypertension trials (SHEP,
      Syst-Eur, Syst-China); a stepped care blood pressure oriented trial (HOT); and
      comparative trials primarily focussing on metabolic aspects and intermediate
      endpoints (ABCD, FACET). On balance, the data seem to indicate that long-acting
      calcium channel blockers score remarkably well in preventing cardiovascular
      complications in diabetic hypertensive patients.

PMID- 10928303
TI  - Behavioral tolerance to the force differentiation effects of diazepam and
      midazolam in rats.
AB  - RATIONALE: Several benzodiazepines (BZs) have been shown to increase the peak
      force of operant responses at doses that increased, decreased, or had no effect
      on response rate, suggesting that operant response force may be a sensitive index
      of BZs' effects rather than solely a correlate of rate-dependent effects. In
      addition, contingent tolerance to the rate-dependent effects of BZs has been
      reported, but the degree of contingent tolerance that develops when the critical
      variable of the task is force of the response has not been explored. OBJECTIVES:
      These experiments examined the effects of acute and repeated oral administration
      of diazepam (DZ) and midazolam (MZ) on a force-differentiation task to explore
      the importance of task requirements on the development of contingent tolerance.
      METHODS: Two groups of rats were trained to press a force-sensing operandum, and
      responses having peak forces falling within fixed lower and upper limits [low
      force (8-10 g) or high force (40-50 g)] were reinforced with water. Acute effects
      of the oral administration of DZ (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg) and MZ (same
      doses) were determined for the discriminated-force task before and after a
      repeated-administration procedure. RESULTS: When administered acutely, both drugs
      increased the peak force of responses in a dose-related manner and concomitantly
      reduced the proportion of reinforced responses, with MZ exhibiting greater
      potency. For the next 36 days, one group received drug before experimental
      sessions and the other group received drug after the experimental session. A
      second dose-effect determination demonstrated that rats chronically dosed with DZ
      or MZ pre-session displayed more contingent tolerance to alterations in peak
      force than rats that had received 36 drug injections postsession, where there was
      no opportunity to practice the force-discrimination response while under the drug
      state. CONCLUSIONS: These results suggest that perceptual motor difficulty of the
      task rather than effort may be an important variable in predicting the degree of
      contingent tolerance that develops. Additionally, these results suggest that both
      behavioral and pharmacological mechanisms are involved in the development of drug
      tolerance to the BZs.

PMID- 10928304
TI  - Modification of behavioral effects of drugs in mice by neuroactive steroids.
AB  - RATIONALE: Neuroactive steroids represent a novel class of potential therapeutic
      agents (epilepsy, anxiety, migraine, drug dependence) thought to act through
      positive allosteric modulation of the GABA(A) receptor. A synthetically derived
      neuroactive steroid, ganaxolone (3alphahydroxy-3beta-methyl-5alpha-pregnan-20
      one), is in phase-II clinical trials for epilepsy. Unlike traditional
      anticonvulsants such as diazepam and phenobarbital, ganaxolone shows equipotent
      suppression of both the seizure activity and the behavioral effects of
      pentylenetetrazol (PTZ) administration. OBJECTIVES: The present study explored
      possible reversal by ganaxolone and related neuroactive steroids of some
      behavioral effects of additional pharmacological challenges. METHODS: Direct
      behavioral observation and photocell-counted locomotor activity of male, Swiss
      Webster mice were made with various compounds alone and in conjunction with
      ganaxolone. RESULTS: Ganaxolone both prevented and reversed PTZ-induced locomotor
      depression in mice. Further, ganaxolone reversed the locomotor depression induced
      by other convulsant/anxiogenic stimuli: bicuculline, picrotoxin and, to a lesser
      extent, yohimbine. Ganaxolone failed to reverse the locomotor stimulation induced
      by cocaine, methamphetamine, dizocilpine, and phencyclidine. In addition to
      ganaxolone, the endogenous neuroactive steroids allopregnanolone and pregnanolone
      and the synthetic neuroactive steroid Co 2-1068 also reversed observed behaviors
      and locomotor depression induced by PTZ. CONCLUSIONS: The present findings
      support the unique pharmacological effects of neuroactive steroids as a novel
      class of positive allosteric modulators of GABA.

PMID- 10928305
TI  - Ipsapirone challenge in aggressive men shows an inverse correlation between 5
      HT1A receptor function and aggression.
AB  - Previous studies have suggested that 5-HT(1A) receptor function is linked to
      aggression. We studied 12 healthy men selected to have high trait levels of
      aggression. They filled in various self-rating measures of aggression, and
      underwent a double blind, crossover challenge with ipsapirone (20 mg orally) and
      a placebo. On both occasions, we measured the endocrine (ACTH, cortisol, growth
      hormone and prolactin), hypothermic and bodily symptom responses every 30 min for
      180 min. We found that subjects with blunted neuroendocrine responses to the
      ipsapirone challenge had significantly higher self-ratings of aggression on a
      number of measures. The same relationship held using the bodily symptom response
      to ipsapirone: blunted responses were associated with higher ratings of
      aggression. We conclude that impaired 5-HT(1A) receptor function is associated
      with increased aggressiveness.

PMID- 10928306
TI  - Fluphenazine levels during maintenance treatment of recent-onset schizophrenia:
      relation to side effects, psychosocial function and depression.
AB  - RATIONALE: The utility of fluphenazine levels during maintenance treatment of
      schizophrenia is still unclear. OBJECTIVES: This study investigated the
      relationship between fluphenazine levels and a variety of clinical measures
      during maintenance treatment of schizophrenia. METHODS: Fluphenazine levels, side
      effects, depression and psychosocial outcome were measured at five time points
      over approximately 1 year in 59 recent onset schizophrenic patients treated with
      a maintenance dose of injectable fluphenazine decanoate. Negative symptoms were
      evaluated at the 1-year endpoint. RESULTS: Fluphenazine levels showed marked
      intraindividual variability even when measurements were restricted to the second
      6 months of treatment, by which time steady state levels should have been
      achieved. No consistent relationship was found between fluphenazine levels and
      any of the outcome measures. CONCLUSIONS: The results of this study suggest that
      fluphenazine plasma levels do not routinely add relevant clinical information
      beyond that of dose in evaluating potential side effects or negative consequences
      during maintenance treatment with the decanoate form of the medication.

PMID- 10928307
TI  - Differential effects of dopamine receptor subtype blockade on performance of rats
      in a reaction-time paradigm.
AB  - RATIONALE: Pharmacological manipulation of the dopaminergic system with
      antipsychotic agents disrupts motor behavior. Although most antipsychotic drugs
      have high affinity for D2 receptors, they also interact with other dopamine
      receptor subtypes. Therefore, the role of each of these receptor subtypes on
      motor performance is unclear. OBJECTIVE: The present study sought to investigate
      the relative importance of D1, D2, and D3 receptors on performance in a
      conditioned reaction-time task known to be extremely sensitive to dysfunction of
      the dopaminergic nigrostriatal pathway. METHODS: Rats were trained to release a
      lever in response to a visual cue within a reaction-time limit to receive a
      reinforcer (45mg food pellet). After the behavior of the rats had stabilized, the
      effects of a D1 (A69024), D2 (eticlopride), and D3 (nafadotride) receptor
      antagonists were assessed. RESULTS: A-69024 had no effect on performance at any
      dose tested (0.3, 0.6, and 1.3 mg/kg s.c.). Nafadotride (0.1, 0.3, and 1 mg/kg
      s.c.) produced only a mild deficit in performance at the highest dose. This
      deficit was characterized by an increase in the number of delayed responses with
      a non-significant decrease in the number of premature responses indicative of non
      specific sedative effects. In contrast, the D2 receptor antagonist eticlopride
      (0.005, 0.01, and 0.02 mg/kg s.c.) produced profound deficits in performance as
      evidenced by a dose-dependent decrease in the number of correct responses. This
      decrease was accompanied by an increase in the number of delayed responses and a
      lengthening of the reaction time at the highest doses. CONCLUSIONS: These results
      provide further evidence that the execution of the reaction-time task is
      dependent preferentially upon the activation of D2 receptors, but not D1 or D3
      receptors.

PMID- 10928308
TI  - Double blind study of tiapride versus haloperidol and placebo in agitation and
      aggressiveness in elderly patients with cognitive impairment.
AB  - OBJECTIVE: The aim of the present study was to compare the efficacy and safety of
      tiapride versus haloperidol and placebo in the treatment of agitation and
      aggressiveness in elderly patients with mild or moderate mental impairment.
      METHOD: This international, multicentre, randomized, double blind, three parallel
      groups study compared efficacy and safety of a 21 -day regimen of tiapride 100
      300 mg/day versus haloperidol 2-6 mg/day and placebo in 306 elderly patients with
      mild or moderate dementia according to DSM III R and behavioural troubles with
      the Multidimensional Observation Scale for the Elderly Subjects (MOSES)
      irritability/aggressiveness subscore ranging from 16 to 30. RESULTS: The
      percentage of responders (defined as patients with at least a 25% MOSES
      irritability/aggressiveness subscore decrease between the inclusion and the end
      of the treatment) was significantly greater in the tiapride (63%, P=0.04) and
      haloperidol (69%, P=0.004) groups than in the placebo group (49%), with no
      significant difference between the active drugs. Similar results were observed
      for the mean MOSES irritability/aggressiveness subscores on D7, D21 and at D(end)
      which were significantly smaller in the tiapride and haloperidol groups than in
      the placebo group. The decrease between D0 and D(end) was significantly greater
      in the tiapride (6.57, P=0.009) and haloperidol groups (6.75, P=0.005) than in
      the placebo group (4.71). The global improvement CGI was significantly better in
      the tiapride and haloperidol groups than in the placebo group (P=0.03 and
      P=0.02). No significant difference was observed between the two active drugs or
      among the three treatment groups for the Folstein's Mini Mental Status scale
      (MMS) total score, and there was no notable change during treatment. The number
      of patients with adverse events, assessed on the Udvalg Kliniske Undersogelser
      scale (UKU), and the number of UKU symptoms were smaller in the tiapride group
      (62 patients, 61%, 212 events) than in the haloperidol group (77 patients, 76%,
      305 events) and identical to that observed in the placebo group (69 patients,
      67%, 234 events). Of interest, the number of patients with at least one
      extrapyramidal symptom was significantly lower (P=0.003) in the tiapride group
      (16 patients, 16%) than in the haloperidol group (34 patients, 34%) and similar
      to that of the placebo group (18 patients, 17%); the difference observed between
      the haloperidol and placebo groups was significant (P=0.008). CONCLUSION:
      Tiapride is not different from haloperidol in the treatment of agitation and
      aggressiveness in elderly patients and better tolerated, in particular with
      significantly fewer extrapyramidal symptoms.

PMID- 10928309
TI  - Motor stimulation following bilateral injection of the group-I metabotropic
      glutamate receptor agonist into the dorsal striatum of rats: evidence against
      dependence on ionotropic glutamate receptors.
AB  - RATIONALE: Group-I metabotropic glutamate receptors (mGluRs) are densely
      expressed in the medium-sized spiny projection neurons of the striatum.
      Activation of the group-I mGluRs in the rat striatum with a selective group-I
      agonist, 3,5-dihydroxyphenylglycine (DHPG), produced locomotion and stereotypical
      behavior. OBJECTIVES: This study was designed to evaluate dependence of DHPG
      stimulated motor behaviors on the ionotropic glutamate receptors [N-methyl-D
      aspartate (NMDA) and kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic
      acid (AMPA)]. METHODS: In chronically cannulated rats, effects on motor activity
      of DHPG injected into the dorsal striatum were examined in the presence or
      absence of the antagonists selective for NMDA or kainate/AMPA receptors. RESULTS:
      Bilateral injections of DHPG (80 nmol) into the dorsal striatum induced a delayed
      locomotion followed by a prolonged stereotypical behavior characterized by the
      repetitive twitching movement of the head and forepaws. Blockade of NMDA
      receptors with intrastriatal injection of the NMDA receptor antagonist, (+/-)-3
      (2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 2.5 nmol), did not
      attenuate the behavioral changes induced by DHPG administration. Conversely, CPP
      unmasked an early onset of locomotion in response to DHPG injection as opposed to
      the delayed locomotion induced by DHPG in the absence of CPP. Pretreatment of
      rats with the kainate/AMPA receptor antagonist, 6,7-dinitroquinoxaline2,3-dione
      (DNQX, 10 nmol), had no effect on DHPG-stimulated behaviors. CPP administered
      alone sedated animals, whereas DNQX given alone did not alter spontaneous
      behavioral activity. CONCLUSIONS: Motor stimulation induced by activation of the
      DHPG-sensitive group-I mGluRs in the striatum is independent upon co-activation
      of NMDA or kainate/AMPA receptors, since the NMDA or the kainate/AMPA receptor
      antagonist had no effect on DHPG-stimulated motor activity.

PMID- 10928310
TI  - Effects of buprenorphine versus buprenorphine/naloxone tablets in non-dependent
      opioid abusers.
AB  - RATIONALE: Buprenorphine is an opioid agonist-antagonist under development in the
      United States as a sublingual medication for treatment of opioid dependence.
      Buprenorphine may be abused; therefore, tablets combining buprenorphine with
      naloxone have been developed with the intent of reducing the abuse risk in people
      physically dependent upon opioids. The characteristics and abuse potential of
      buprenorphine and buprenorphine/naloxone tablets in non-dependent opioid abusers
      have not been determined. Non-parenteral abuse of opioids such as buprenorphine
      may be more likely in people who have less severe substance abuse disorders
      (e.g., are not physically dependent upon opioids). OBJECTIVES: To assess the
      abuse potential of sublingual buprenorphine and buprenorphine/naloxone tablets in
      non-dependent opioid abusers. METHODS: Subjects (n=7) were tested with sublingual
      buprenorphine (4, 8, 16 mg), sublingual buprenorphine/naloxone (1/0.25, 2/0.5,
      4/1, 8/2, 16/4 mg), as well as intramuscular hydromorphone as an opioid agonist
      control (2, 4 mg) and placebo in laboratory sessions conducted twice per week.
      Dosing was double-blind and double-dummy. RESULTS: The higher doses of both
      buprenorphine and buprenorphine/naloxone produced similar opioid agonist-like
      effects. The onset of these effects was slowed, consistent with the sublingual
      route of administration, and the magnitude of effects was moderate. There was no
      evidence to suggest the addition of naloxone attenuated buprenorphine's opioid
      agonist effects in this population when buprenorphine was delivered by the
      sublingual route. CONCLUSIONS: These results suggest that sublingual
      buprenorphine and buprenorphine/naloxone may both be abused by opioid users who
      are not physically dependent upon opioids.

PMID- 10928311
TI  - Associative and non-associative fentanyl tolerance in the rat: evaluation of
      cross tolerance with mu-and kappa-specific opioids.
AB  - RATIONALE: Associative tolerance to the analgesic effects of morphine is most
      pronounced when morphine is paired with a distinctive context at a long interdose
      interval (IDI). In contrast, morphine administered at a short IDI promotes the
      development of non-associative tolerance and disrupts the acquisition of
      associative tolerance. The impact of IDI on the development of associative
      tolerance to opioids other than morphine has not been investigated previously.
      OBJECTIVES: This research examined associative and non-associative tolerance to
      the analgesic effects of fentanyl in rats. Cross tolerance for these two forms of
      tolerance with morphine (mureceptor agonist) and U50,488H (kappa-receptor
      agonist) analgesia was also investigated. METHODS: Animals were given eight
      fentanyl injections (0.10 mg/kg) paired or unpaired with a distinctive context at
      either a 3-h (short) or 96-h (long) IDI. Subjects were then tested for tolerance
      in the distinctive context using the tail-flick procedure and dose-response curve
      methodology. RESULTS: At the short IDI, animals developed non-associative
      tolerance to fentanyl that was receptor specific, i.e., cross tolerant with
      morphine analgesia but not with U50,488H analgesia. At the long IDI, fentanyl
      tested animals displayed tolerance that appeared to be controlled primarily by
      associative processes. This associative form of tolerance was also receptor
      specific, displaying cross tolerance with morphine but not with U50,488H.
      CONCLUSIONS: The impact of IDI on the development of non-associative and
      associative fentanyl tolerance is consistent with findings obtained with morphine
      showing that conditions conducive to the development of non-associative tolerance
      disrupt the acquisition of associative tolerance. The cross-tolerance data,
      however, did not parallel previous research examining the cross-tolerance
      profiles of associative and non-associative morphine tolerance.

PMID- 10928312
TI  - Methoclocinnamox: time course of changes in alfentanil-reinforced responding in
      rhesus monkeys.
AB  - RATIONALE: Methoclocinnamox (MC-CAM) possesses initial partial micro-opioid
      agonist activity with subsequent long-lasting micro-antagonist effects. This
      profile of activity is similar to that of buprenorphine, a compound with proposed
      use in the treatment of opioid abuse, suggesting a possible therapeutic use for
      MC-CAM as well. OBJECTIVE: The current study assessed the time course of the
      ability of MC-CAM and buprenorphine to antagonize the reinforcing effects of
      alfentanil and compared this with that of buprenorphine. METHODS: Rhesus monkeys
      self-administered a range of doses of alfentanil (0.03-1 microg/kg per injection)
      under a fixed-ratio 30, time-out 45 s schedule of i.v. drug delivery. MC-CAM was
      substituted for alfentanil on occasion, and a dose of 1.0 mg/kg MC-CAM or
      buprenorphine was given prior to sessions in which alfentanil was available. In
      the pretreatment studies, a wider range of alfentanil doses was utilized (0.03-30
      microg/kg per injection). RESULTS: MC-CAM maintained self-administration behavior
      and was nearly equipotent with buprenorphine as a reinforcer in this paradigm.
      Both drugs, when given prior to a session in which alfentanil was available,
      produced a decrease in the reinforcing potency of alfentanil. The antagonist
      effects of the pretreatments were largest 30 min following administration and
      decreased over the next several days. The duration of MC-CAM's antagonism of
      alfentanil was approximately 4 days: the duration of buprenorphine as an
      antagonist was approximately 2 days. CONCLUSION: These data suggest that MC-CAM
      has a longer duration of antagonist effects than buprenorphine and it may
      therefore have an advantage in the treatment of opioid abuse.

PMID- 10928313
TI  - High 5HT2A receptor occupancy in M100907-treated schizophrenic patients.
AB  - RATIONALE: Selective drugs are required to test the hypothesis whether
      antipsychotic effects may be induced or modulated by 5HT(2A) receptor antagonism.
      M100907 (previously known as MDL 100,907) is a highly selective 5HT(2A)
      antagonist in clinical development. OBJECTIVE: To test if the suggested clinical
      dose of 20 mg M100907 daily induces high 5HT(2A) receptor occupancy in patients
      with schizophrenia. METHODS: The 5HT(2A) receptor occupancy was determined in two
      patients with schizophrenia treated with M100907, 20 mg once a day. Positron
      emission tomography (PET) with (11)C-labeled M100907, was performed prestudy and
      under steady state conditions. Clinical ratings were performed weekly. RESULTS:
      Clinical treatment with M100907, 20 mg daily induced a very high 5HT(2A) receptor
      occupancy in the frontal cortex of both patients (>90%). M100907 was well
      tolerated. One patient improved minimally and one patient became minimally worse
      during treatment. CONCLUSIONS: The results confirm that an oral dose of 20 mg per
      day ensures adequate 5HT(2A) receptor occupancy for clinical proof of concept.
      The sample is too small to allow conclusions about the clinical effect.

PMID- 10928314
TI  - The loudness dependency of the auditory evoked N1/P2-component as a predictor of
      the acute SSRI response in depression.
AB  - RATIONALE: A serotonergic dysfunction is supposed to play a pathogenetic role in
      depression, but there is a considerable number of non-responders in the acute
      treatment of depression with serotonergic agents like SSRI. Thus, an indicator of
      central serotonergic activity could lead to a more specific pharmacological
      treatment of depression. In animal and human data there is a growing amount of
      evidence that a strong loudness dependency of late auditory evoked potentials
      (LDAEP) is an indicator of low serotonergic activity and vice versa. OBJECTIVE:
      In 29 depressive inpatients (DSM-III-R diagnosis 296.x in 28 patients, 300.4 in
      one patient), the hypothesis was tested that a strong LDAEP prior to treatment
      can predict a better clinical outcome under SSRI treatment over 4 weeks. RESULTS:
      Patients with a strong pre-treatment LDAEP had a significantly greater decrease
      of depressive symptoms (Hamilton Scale for Depression) after 4 weeks than
      patients with a flat LDAEP. Significantly more responders fell into the group
      with a high LDAEP. Contrary to what might be expected, a second recording in a
      subsample of 19 patients after 4 weeks of treatment failed to show changes in the
      LDAEP. CONCLUSION: Our finding confirms the hypothesis that a strong LDAEP,
      indicating a low serotonergic activity, is related to a favorable response to
      acute SSRI treatment in depression. The LDAEP is a promising tool for the
      prediction of response to serotonin agonists in depression and it seems to be of
      clinical importance.

PMID- 10928315
TI  - Reductions in ethanol, phencyclidine, and food-maintained behavior by naltrexone
      pretreatment in monkeys is enhanced by open economic conditions.
AB  - RATIONALE: Previous results suggested that naltrexone had opioid-selective
      effects on behavior reinforced by orally delivered drugs and food. The present
      study explores the possibility that previous results were due to presentation of
      the reinforcers in a closed economy (all reinforcers earned by subjects) and that
      naltrexone's effect may be nonselective under conditions of an open economy
      (earned reinforcers supplemented by unearned). OBJECTIVES: The purpose of this
      experiment was to compare the effect of naltrexone on ethanol-, phencyclidine
      (PCP), and food-reinforced responding under several open-economy conditions and
      compare them with those from a previous report using a closed economy. METHODS:
      Ethanol (8% w/v), PCP (0.25 mg/ml), and food were available under independent,
      concurrent, progressive-ratio (PR) schedules with water, and side positions were
      alternated daily. Three naltrexone doses (0.1, 0.3, and 1.0 mg/kg) were
      administered in a nonsystematic order for 5 days, with the 5-day pretreatment
      period serving as a control. Four economic conditions were compared: data for the
      closed economy were taken from a recently completed experiment using the same
      monkeys. The open-economy condition was varied by allowing free access to 1, 2 or
      3 times the amount of drug or food that was earned during session later during a
      postsession time-out period. RESULTS: In an open economy, naltrexone
      nonselectively suppressed ethanol, PCP, and food-maintained behavior, in contrast
      to results in the previous study which used a closed economy, wherein naltrexone
      did not significantly suppress food- or PCP self-administration. As the economy
      for PCP, ethanol, and food became more open, the suppressant effects of
      naltrexone increased and, in many animals, behavioral measures decreased to zero.
      CONCLUSION: These results indicated that the economy under which drugs and food
      are self-administered is an important determinant of the effectiveness of
      naltrexone's ability to suppress drug- and food-reinforced behavior. The results
      also suggest that testing medications for drug abuse using a food control
      condition under a closed economy can bias the results toward a conclusion of
      selectivity of the treatment medication for drug-reinforced behavior.

PMID- 10928316
TI  - Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor
      agonist, LY379268 and comparison with the atypical antipsychotic, clozapine.
AB  - RATIONALE: Recent studies using phencyclidine (PCP) as a model for psychosis have
      implicated metabotropic glutamate (mGlu) receptors in schizophrenia. We have
      shown, using an automated motor activity monitoring system, that selective group
      II mGlu receptor agonists attenuate PCP (5 mg/kg)-evoked increases in ambulations
      and fine motor movements with similar profiles to the atypical antipsychotic,
      clozapine. OBJECTIVE AND METHODS: Because the automated system does not
      discriminate between specific PCP-evoked behaviors, in this paper we examined the
      effects of the potent mGlu2/3 receptor agonist LY379268 on PCP-evoked behaviors
      as assessed by observational methods. Furthermore, we have compared the actions
      of LY379268 to the atypical antipsychotic clozapine. RESULTS: LY379268 and
      clozapine reduced the expression of PCP-induced falling, turning and back
      pedaling in a dose-dependent manner. Thirty minutes post-PCP administration, 1
      mg/kg LY379269 reduced falls and turns by 89% and 53%, respectively, and 1 mg/kg
      clozapine attenuated turning by 70%. Interestingly, low doses of clozapine
      increased PCP-elicited falls. Back-pedaling was particularly sensitive to
      LY379268 and clozapine, with 1 mg/kg of either agent completely abolishing back
      pedaling 30 min after PCP administration. However, in contrast to LY379268,
      attenuation of these behaviors by clozapine only occurred at doses that augmented
      PCP-evoked ataxia. Furthermore, LY379268 did not affect PCP-evoked forepaw
      treading. CONCLUSIONS: These results indicate that mGlu2/3 receptors do not
      mediate a generalized reduction in motor activity, but instead selectively
      modulate specific PCP behaviors, further implicating group II mGlu receptors as
      viable drug targets in the treatment of schizophrenia.

PMID- 10928317
TI  - Pharmacological characterization of the nociceptin receptor mediating
      hyperphagia: identification of a selective antagonist.
AB  - RATIONALE: Central injections of nociceptin (NC) stimulate feeding in rats.
      OBJECTIVE: The present study evaluated the effect of N-terminal partial sequences
      or analogues of NC on food intake in male Wistar rats, to characterize
      pharmacologically the NC receptor mediating the hyperphagic effect. METHODS: NC
      and related peptides were injected into the lateral (LV) or third (3V)
      cerebroventricle in freely feeding rats. RESULTS: In the LV, NC stimulated
      feeding. The N-terminal fragment NC(1-13)NH2 proved to be the least active
      sequence with hyperphagic activity; NC(1-12)NH2 and NC(1-9)NH2 were inactive.
      [Phe(1)psi(CH2-NH)Gly(2)]NC(1-13)NH2 ([F/G)]NC(1-13)NH2), an analogue of NC(1
      13)NH2, markedly stimulated feeding and, coadministered in the LV with NC, never
      reduced the hyperphagic effect of the natural sequence. These findings suggest
      that [F/G)]NC(1-13)NH2, which has been reported to act as a NC receptor
      antagonist in peripheral tissues, behaves as a full agonist at the central NC
      receptors controlling feeding. The hyperphagic potencies of NC and [F/G)]NC(1
      13)NH2 were much higher following injection into the 3V than in the LV. Another
      analogue of NC(1-13)NH2, namely [Nphe(1)]NC(1-13)NH2, injected into the 3V did
      not stimulate feeding, but reduced the effect of NC. [Nphe(1)]NC(1-13)NH2 at a
      dose of 16.8 nmol/rat significantly reduced, and at 168 nmol/rat almost
      completely abolished the effect of NC (1.68 nmol/rat). The latter dose of
      [Nphe(1)]NC(1-13)NH2 significantly reduced also feeding induced by food
      deprivation, but did not modify the hyperphagic effect of neuropeptide Y (0.3
      nmol/rat). CONCLUSIONS: The present results confirm the orexigenic effect of NC
      in freely feeding rats and indicate that [Nphe(1)]NC(1-13)NH2 may represent a
      selective NC receptor antagonist to study the physiological and
      pathophysiological role of NC in feeding behaviour.

PMID- 10928319
TI  - Role of catecholaminergic and cyclic AMP systems in psychological dependence on
      phencyclidine: a study in mutant mice.
AB  - Catecholaminergic and/or cyclic AMP (cAMP) systems have been demonstrated to be
      involved in the development of drug dependence. We investigated the involvement
      of both systems in psychological dependence on phencyclidine (PCP) by using
      tyrosine hydroxylase (TH) heterozygous (TH+/-) and cAMP response element binding
      protein (CREB) binding protein (CBP) heterozygous (CBP+/-) mice. PCP (8 mg/kg)
      induced place preference in wild-type mice pretreated with PCP (10 mg/kg once a
      day for 28 days). In these mice, the level of cAMP in the striatum, but not in
      the thalamus, was increased one day after the last injection of PCP (10 mg/kg).
      In TH+/- and CBP+/- mice pretreated with PCP (10 mg/kg per day for 28 days),
      however, no PCP (8 mg/kg)-induced place preference was observed. The level of
      cAMP in the striatum was increased in CBP+/- mice, but not TH+/- mice.
      Furthermore, we have demonstrated that the place preference induced by PCP is
      attenuated by 6-hydroxydopamine, a dopaminergic neurotoxin, and (+) SCH-23390, a
      dopamine-D1 receptor antagonist, but not by DSP-4, a noradrenergic neurotoxin,
      and (-) sulpiride, a dopamine-D2 receptor antagonist. These findings suggest that
      catecholamines and CBP are involved in the development of psychological
      dependence on PCP and that changes in dopaminergic and/or cAMP systems induced by
      repeated PCP treatment play an important role in the addiction to PCP.

PMID- 10928318
TI  - The serotonin-1A receptor antagonist WAY-100635 modifies fluoxetine's
      antidepressant-like profile on the differential reinforcement of low rates 72-s
      schedule in rats.
AB  - RATIONALE: Recent preclinical and clinical data suggest that co-administration of
      a serotonin-1A (5-HT-1A) receptor antagonist with an antidepressant drug has
      greater therapeutic efficacy than when the antidepressant drug is administered
      alone. OBJECTIVE: The purpose of the present experiment was to determine whether
      pretreatment with the selective 5-HT-1A receptor antagonist N-[2-[4-(2
      methoxyphenyl)- 1-piperazinyl]ethyl]-N-(pyridinyl)cyclohexanecarboxamide (WAY
      100635; 0.003, 0.03, 0.3 mg/kg, s.c.) would alter the effects of the
      antidepressant fluoxetine (2.5-10 mg/kg, i.p.) on the differential reinforcement
      of low-rate 72-s (DRL 72-s) schedule. The DRL 72-s schedule is a behavioral
      screen selective and sensitive to antidepressant drugs. RESULTS: WAY-100635 had
      no behavioral effects on its own. The lower doses of fluoxetine (2.5 mg/kg and 5
      mg/kg) had no effects, but 10 mg/kg increased reinforcement rate without
      affecting response rate. The increase in reinforcement rate was blocked by
      pretreatment with 0.03 mg/kg and 0.3 mg/kg WAY-100635, although the combination
      of fluoxetine and WAY-100635 also significantly reduced response rate.
      Interestingly, 0.003 mg/kg or 0.03 mg/kg WAY-100635 administered with 5.0 mg/kg
      fluoxetine increased reinforcement rate, even though this dose of fluoxetine had
      no effect on performance. CONCLUSION: These data demonstrate that the behavioral
      effects of fluoxetine are modified by 5-HT-1A receptor blockade.

PMID- 10928320
TI  - Aquaporin water channel in salivary glands.
AB  - Water secretion from salivary glands, which are innervated by parasympathetic and
      sympathetic nerves, occurs in response to the stimulation by neurotransmitters.
      In general, parasympathetic or sympathetic stimulation produces a high flow of
      saliva as a result of the activation of M3 muscarinic or alpha1-adrenergic
      receptors, respectively. The secretory mechanisms of fluid secretion were
      osmotically regulated in response to a transepithelial ion gradient generated by
      ion transport systems that were located in the apical or basolateral membranes of
      the acinar cells. Recently, the identification of water-specific channels, or
      aquaporins (AQPs), in many mammalian tissue and cell types has provided insight
      into the molecular basis of water movement across biological membranes. It has
      been reported that several AQPs are expressed in salivary glands and especially
      AQP5 plays an important role in fluid secretion. This review will focus on the
      role of AQP5 in the movement of water across the apical plasma membrane in
      relation to the physiology and pathophysiology of salivary glands.

PMID- 10928321
TI  - Nicotine-induced noradrenaline release from the isolated rat stomach by
      activation of L- and N-type calcium channels.
AB  - We examined the effect of nicotine on the release of endogenous noradrenaline
      (NA) from the isolated, vascularly perfused rat stomach. The stomach was perfused
      via the coeliac artery with Krebs-Ringer solution containing 10 microM pargyline
      at a constant flow rate of 4 ml per minute. Nicotine was once applied in the
      perfusion medium for 2 min. Nicotine (10(-6) - 10(-4) M) evoked NA release in a
      concentration-dependent manner. The nicotine (3 x 10(-5) M)-evoked NA release was
      abolished by hexamethonium and tetrodotoxin. Diltiazem and isradipine [blockers
      of L-type voltage-activated calcium channel (VACC)] and omega-conotoxin GVIA (a
      blocker of N-type VACC) also abolished this nicotine-evoked NA release.
      Previously we reported that N-type, but not L-type, VACCs are located on the
      gastric postganglionic sympathetic nerve terminals, since the NA release evoked
      by electrical stimulation of periarterial nerves around the left gastric artery
      (postganglionic sympathetic nerves) was abolished by omega-conotoxin GVIA, but
      not by diltiazem (Yokotani et al., Jpn. J. Pharmacol. 78, 75- 77, 1998). From
      these results, it was suggested that nicotine activates nicotinic acetylcholine
      receptors located on the sympathetic ganglia, thereby evoking NA release by
      activation of L-type VACC located on the gastric sympathetic ganglia and N-type
      VACC probably located on the sympathetic nerve terminals in the rat stomach.

PMID- 10928322
TI  - Electrophysiological and cardiohemodynamic effects of AH-1058, a new type calcium
      channel blocker, assessed by the in vivo canine model.
AB  - AH-1058 (4-(5H-dibenzo[a, d]cyclohepten-5-ylidene)- 1-[(E)-3-(3-methoxy-2
      nitro)phenyl-2-propenyl]piperidine hydrochloride) is a novel calcium channel
      blocker whose chemical structure is quite different from those of typical calcium
      channel blockers. In this study, electrophysiological and hemodynamic effects of
      AH-1058 were assessed in the halothane-anesthetized, closed-chest canine model.
      Intravenous administration of a canine antiarrhythmic dose of 100 microg/kg of AH
      1058 (n = 6) did not affect the cardiovascular variables, except that the cardiac
      output was decreased at 30 min after the drug administration. Additional
      administration of 200 microg/kg of AH-1058 (n = 6) suppressed the sinus nodal
      automaticity, AV nodal conduction and ventricular contraction and decreased the
      mean blood pressure, cardiac output and double product. The effects gradually
      appeared, while no change was detected in the intraventricular conduction,
      ventricular repolarization period, ventricular effective refractory period,
      preload to the left ventricle and total peripheral vascular resistance during the
      observation period of 30 min. The cardiosuppressive effects of AH-1058 can be
      explained by its calcium channel blocking action demonstrated in a previous in
      vitro experiment, while the lack of the effect on the vascular resistance would
      suggest that AH-1058 may become a slow-acting cardioselective calcium channel
      blocker.

PMID- 10928323
TI  - Effects of rolipram, a selective inhibitor of phosphodiesterase 4, on
      hyperlocomotion induced by several abused drugs in mice.
AB  - The effects of rolipram, a selective inhibitor of phosphodiesterase 4, on the
      hyperlocomotion induced by several abused drugs (methamphetamine, morphine and
      phencyclidine) and a dopamine D1-receptor agonist (SKF81297; (+/-)-6-chloro-7,8
      dihydroxy-1-phenyl-2,3 ,4,5-tetrahydro-1H-3-benzazepin hydrobromide) in mice were
      investigated. Methamphetamine (0.5-2.0 mg/kg), morphine (5.0-20 mg/kg),
      phencyclidine (1.25-5.0 mg/kg) and SKF81297 (2.5-10 mg/kg) each induced dose
      dependent hyperlocomotion. A low dose (1.0 mg/kg) or moderate dose (3.2 mg/kg) of
      rolipram suppressed methamphetamine (2.0 mg/kg)- and morphine (20 mg/kg)-induced
      hyperlocomotion, but not phencyclidine (5.0 mg/kg)-induced hyperlocomotion. These
      results suggest that cAMP in the brain is involved in methamphetamine- and
      morphine-induced hyperlocomotion, while the underlying mechanism(s) of
      phencyclidine-induced hyperlocomotion may be different from those of
      methamphetamine- and morphine-induced hyperlocomotion. It is well known that
      methamphetamine- and morphine-induced hyperlocomotion are mediated by the
      dopaminergic system and that interaction between postsynaptic D1- and D2
      receptors may play an important role in the expression of various dopamine
      mediated behaviors. In the present study, SKF81297 (10 mg/kg)-induced
      hyperlocomotion was significantly but not completely suppressed by the highest
      dose of rolipram (10 mg/kg). Therefore it is unlikely that postsynaptic D1
      receptor-mediated functions are involved in the suppressive effects of rolipram
      on methamphetamine- and morphine-induced hyperlocomotion. These results suggest
      that rolipram may inhibit methamphetamine- and morphine-induced hyperlocomotion
      via increase cAMP levels at D2-receptors.

PMID- 10928324
TI  - Anti-apoptotic effect of acetyl-l-carnitine and I-carnitine in primary cultured
      neurons.
AB  - Although exogenously administered acetyl-l-carnitine (ALCAR, (2-acetoxy-3
      carboxypropyl)-trimethylammonium) and l-carnitine (LC, (3-carboxy-2
      hydroxypropyl)-trimethylammonium) prevent brain damage in several ischemic
      models, the protective mechanism of these compounds remains unclear. Here, we
      evaluated the effect of ALCAR and LC in primary cultured neurons from the
      cerebral cortex, striatum and thalamus of 18-day-old rat embryos. Deprivation of
      the serum from cultured medium for 3 days reduced the number of viable cells and
      mitochondrial activity and induced cell death with characteristics of apoptosis
      such as DNA fragmentation, nuclear condensation and histone-DNA release into the
      cytoplasm. ALCAR (1 - 100 microM) and LC (1 - 100 microM) promoted neuronal
      survival and mitochondrial activity in a concentration-dependent manner.
      Moreover, these compounds attenuated DNA fragmentation and nuclear condensation
      in cultured neurons and significantly decreased histone-DNA release into the
      cytoplasm. These results indicate that anti-apoptotic actions of ALCAR and LC
      contribute to their neuroprotective effect.

PMID- 10928325
TI  - The effect of the prostaglandin I2 analogue OP-2507 on adrenaline-induced
      pulmonary edema in rabbits and analysis of hemodynamic changes.
AB  - This study was carried out to understand the onset mechanism of adrenaline (ADR)
      induced pulmonary edema (PE) and the effect of drugs related to the arachidonate
      cascade in a rabbit model. ADR was administered intravenously by a bolus
      injection to the rabbits at 50, 75 and 100 microg/kg. To evaluate the severity of
      PE, the lung-water ratio (LWR) was calculated as a ratio of the difference
      between wet and dry lung weight to dry lung weight. The PE incidence and LWR
      exhibited a dose-dependent increase, and LWR correlated with the left atrial
      pressure (LAP). The involvement of the arachidonate cascade was evaluated by the
      co-administration of flurbiprofen, a cyclooxygenase inhibitor; ozagrel, a
      thromboxane synthase inhibitor; and OP-2507 (15-cis-(4-n-propylcyclohexyl)
      6,17,18, 19,20-pentanor-9-deoxy-6,9-alpha-nitriloprostaglandin F1 methyl ester),
      a prostaglandin I2 analogue. Co-treatment of the rabbits with ADR and
      flurbiprofen resulted in an increase in LAP and the incidence of PE, whereas co
      administration of ozagrel did not exhibit any significant changes in the measured
      parameters. Conversely, OP-2507 reduced the LAP, PE incidence and LWR when co
      administered with ADR. Rabbits co-treated with OP-2507 displayed an improved
      cardiac function. The results of these studies demonstrated the effectiveness of
      OP-2507 in protecting the lung and cardiac function from the ADR-induced PE.

PMID- 10928326
TI  - Effect of Choto-san, a Kampo medicine, on the cerebral blood flow autoregulation
      in spontaneously hypertensive rats.
AB  - To clarify the mechanism of the benefical effect of Choto-san on cerebral
      circulation in hypertensive patients, the influence of Choto-san on cerebral
      blood flow (CBF) during hemorrhagic hypotension was evaluated in 10- to 11-month
      old spontaneously hypertensive rats. The lower limit of CBF autoregulation,
      defined as the mean arterial blood pressure at which CBF decreased by 10% of the
      baseline value, was dose-dependently lowered when Choto-san (0.5 - 2.0 g/kg per
      day, p.o.) was administered for 14 consecutive days. Uncariae Ramulus et Uncus
      (150 mg/kg per day, p.o.), one of the crude drug components of Choto-san, showed
      an effect equivalent to that of Choto-san. The action of Choto-san (2.0 g/kg per
      day, p.o.) or Uncariae Ramulus et Uncus on the autoregulatory response of
      cerebral vessels was eliminated by treatment with N(G)-nitro-L-arginine methyl
      ester (10 mg/kg, i.v.), an inhibitor of nitric oxide synthase. These results
      suggested that the activation of nitric oxide synthase by Uncariae Ramulus et
      Uncus contributed to at least part of the improvement in the cerebral circulation
      caused by Choto-san.

PMID- 10928327
TI  - Inhibitory mechanism of papaverine on the smooth muscle of guinea pig urinary
      bladder.
AB  - In guinea pig urinary bladder, the hyperosmotic 65 mM KCI (H-65K+)- or carbachol
      (CCh)-induced contraction was inhibited by an addition of papaverine in a
      concentration-dependent manner. The cAMP content of the muscle in the presence of
      H-65K+ or CCh was increased by papaverine only at the higher concentration of 100
      microM, but cGMP content was not affected by papaverine. Forskolin, compared with
      papaverine, increased cAMP content in a concentration-dependent manner, and
      nitroprusside did not significantly increase cGMP content. In a fura 2 loaded
      muscle, papaverine did not affect an increase of [Ca2+]i level by high K+ or CCh.
      The increase of oxidized flavoprotein (FPox) fluorescence and muscle contraction
      in the presence of H-65K+ or CCh was decreased by papaverine (1 - 100 microM),
      and the increase of pyridine nucleotide (PNred) fluorescence was not affected by
      papaverine. In summary, it was concluded that papaverine induced relaxation by
      inhibiting mitochondrial respiration in guinea pig urinary bladder as well as
      ileum. Moreover, it is proposed that the mechanism of papaverine-induced
      relaxation in the smooth muscle, which shows predominantly a metabolic dependency
      on its contraction, is an inhibition of mitochondrial respiration.

PMID- 10928328
TI  - Behavioral effects of plant-derived essential oils in the geller type conflict
      test in mice.
AB  - The present study was conducted to further explore plant-derived essential oils
      that possess an anticonflict effect using the Geller type conflict test in ICR
      mice. The benzodiazepine anxiolytic diazepam increased the response (lever
      pressing) rate during the alarm period (i.e., an anticonflict effect), but the 5
      HT1A partial agonist buspirone did not. Oils of juniper, cypress, geranium and
      jasmine did not produce any effect in this test. Frankincense oil decreased the
      response rate during the safe period at 1600 mg/kg, but did not exhibit any
      effect on the response rate during the alarm period. In contrast, lavender oil
      increased the response rate during the alarm period in a dose-dependent manner in
      the same manner as diazepam. These results indicate that not only rose oil but
      also lavender oil possess an anticonflict effect in mice.

PMID- 10928329
TI  - Effects of intraplantar morphine in the mouse formalin test.
AB  - We studied the effects of intraplantar morphine in the formalin test in mice.
      Intraplantarly administered morphine (30 - 300 microg) induced analgesic effects
      at lower doses than intraperitoneally administered morphine. Following the
      administration of [3H]morphine, the % of radioactivity present in brain was the
      same by either route. In contrast, higher radioactivity values appeared in the
      injected paw in those mice intraplantarly injected. Since local morphine induces
      analgesia at doses lower than the intraperitoneally administered drug, especially
      in the second phase of the test, and the access to brain is undistinguishable, we
      propose that local morphine enhances central opiate analgesia in the formalin
      test in mice.

PMID- 10928330
TI  - Acceleration by KW-5092 of intestinal motility associated with acetylcholine
      release in vivo.
AB  - Effect of KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]ethyl]-2-
      imidazolidinylidene]propanedinitrile fumarate) on intestinal motility and release
      of endogenous acetylcholine (ACh) were measured simultaneously in the small
      intestine of anesthetized dog using the in vivo microdialysis method.
      Intraarterial and intravenous administrations of KW-5092 accelerated the
      intestinal motility and increased dialysate ACh concentrations. These KW-5092
      induced responses paralleled the increase in blood concentration of KW-5092.
      Thus, the acceleration of intestinal motility by KW-5092 was found in vivo to be
      associated with an increase in ACh release from the intestinal cholinergic
      neurons.

PMID- 10928331
TI  - Botulinum toxin C3 inhibits hyperalgesia in mice with partial sciatic nerve
      injury.
AB  - Mice with partial ligation of the sciatic nerve exhibited marked increase in the
      second phase nociceptive biting and licking behavior following intraplantar
      injection of formalin. The intrathecal pretreatment with botulinum toxin C3 dose
      dependently attenuated the hyperalgesia in the second phase. These results
      suggest that a small G protein, Rho, and its downstream mechanisms are involved
      in the hyperalgesia following partial nerve injury.

PMID- 10928332
TI  - 2-Bromoethylamine, a suicide inhibitor of tissue-bound semicarbazide-sensitive
      amine oxidase.
AB  - Various mammalian tissues contain plasma membrane-bound amine oxidase, termed
      semicarbazide-sensitive amine oxidase (SSAO). In the present study, 2
      bromoethylamine has been studied with regard to inhibitory properties towards
      tissue-bound SSAO in rat lung. Without preincubation, 2-bromoethylamine was a
      competitive and reversible SSAO inhibitor with a Ki value of 2.5 microM. After
      preincubation, it time-dependently and non-competitively inhibited SSAO activity,
      probably by forming the covalently-bound enzyme-inhibitor adduct. The data
      presented suggest that 2-bromoethylamine may act as a suicide inhibitor of SSAO.

PMID- 10928333
TI  - Current concepts of anemia management in chronic renal failure: impact of NKF
      DOQI.
AB  - Since the introduction of recombinant human erythropoietin (rHuEPO) into clinical
      nephrology practice 10 years ago, there has been a slow increase in hemoglobin
      (Hgb) levels, but most patients with the anemia of chronic renal failure are
      still moderately anemic and have not achieved the target Hgb (11 to 12 g/dL)
      recommended by the NKF-DOQI anemia guidelines. Functional iron deficiency,
      insufficient rHuEPO doses and comorbid factors such as inflammation/infection
      have been the major reasons for not achieving this target. By optimizing iron
      stores with regular infusions of intravenous iron in the hemodialysis patient
      (who has significant blood [iron] losses related to the hemodialysis procedure),
      and giving adequate amounts of rHuEPO, preferably subcutaneously instead of
      intravenously, the NKF-DOQI recommended target Hb can be achieved in the majority
      of patients so treated.

PMID- 10928334
TI  - Lessons from NKF-DOQI: iron management.

PMID- 10928335
TI  - Trends in erythropoietin therapy in the U.S. dialysis population: 1995 to 1998.
AB  - Anemia is an important cause of morbidity, and may be associated with increased
      mortality in patients with end-stage renal disease (ESRD) receiving dialysis.
      Therapy with recombinant human erythropoietin (rHuEPO) has revolutionized the
      care of ESRD patients, but this is a costly medication and concerns have been
      expressed about whether the outcome, as measured by achieved hematocrit (Hct),
      could be improved. The number and proportion of ESRD patients receiving rHuEPO
      increased steadily from 1995 to 1998, as did the dose of rHuEPO per patient. The
      amount of intravenous iron administered to patients increased markedly over the
      study period. The patients' mean hematocrit also rose, but proportionally less
      over the study period. The increase in both the amounts of payments per patient
      for rHuEPO, and the number of patients receiving rHuEPO over this time has
      resulted in a marked increase in the total costs to Medicare for this therapy. We
      suggest that a combination of payment regulations, provider financial
      opportunities and disincentives, and patient resistance to the effects of rHuEPO,
      as a result of both iron deficiency and inflammation, largely explain the
      findings.

PMID- 10928336
TI  - Impact of hematocrit on morbidity and mortality.
AB  - It has been 10 years since epoetin-alpha was approved by the federal Food and
      Drug Administration for use in end-stage renal disease patients. Over this period
      of time, clinical studies have shown a relationship between the correction of
      anemia and improved cardiac function, cognitive ability, sexual function, and
      exercise capacity. Recent large epidemiological studies have shown that mortality
      and morbidity are reduced when the hematocrit (Hct) level is in the range 33% to
      36%, and the National Kidney Foundation's Dialysis Outcomes Quality Initiative
      (NKF-DOQI) guidelines recommend a target Hct of 33% to 36% to enhance patient
      outcomes. The most recent mortality studies show that Hcts less than 30% (or
      hemoglobins less than 110 gm/L) are associated with an 18% to 40% increased
      associated risk of death and hospitalizations. Higher Hcts in the 33% to 36%
      range appear to be associated with a 7% reduced risk of death and
      hospitalizations compared with patients with Hcts of 30% to less than 33%.
      Patients with sustained Hcts of 33% to 36% over 1 year appear to have the best
      outcome compared with patients with Hcts that fall. These studies suggest that
      the factors that may influence patients' ability to move into higher Hct ranges
      need to be determined to enhance patient outcomes. Dramatic improvement in
      hemodialysis patient Hct levels has occurred since 1989. Mortality and
      hospitalization studies support the NKF-DOQI target Hct range of 33% to 36% as
      providing the best associated outcomes.

PMID- 10928337
TI  - The impact of anemia correction on cardiovascular disease in end-stage renal
      disease.
AB  - Cardiovascular disease is a major cause of mortality and morbidity in patients
      with end-stage renal disease. Anemia, a result of erythropoietin deficiency, is
      associated with increased all-cause and cardiovascular mortality in this
      population, and predisposes patients to the development of symptomatic heart
      disease. Anemia is also associated with the development and progression of left
      ventricular echocardiographic disorders, which strongly predict cardiac failure
      and death. Left ventricular dilatation with compensatory hypertrophy, the major
      pattern of echocardiographic disease progression in hemodialysis patients, is a
      particularly strong predictor of late mortality. Partial correction of anemia
      with recombinant human erythropoietin likely reduces left ventricular mass and
      volume. Complete correction of anemia may prevent progressive left ventricular
      dilatation in patients with normal left ventricular volumes. A recent trial,
      however, reports excess mortality and vascular access loss in patients with
      preexisting symptomatic heart disease when anemia was completely corrected.
      Consequently, hematocrit target ranges above 32% to 36% cannot be recommended in
      this population. In patients without symptomatic heart disease, it is not
      possible to conclude that potential benefits derived from a normalized hematocrit
      will outweigh potential risks.

PMID- 10928339
TI  - Physiological and pharmacodynamic considerations for route of EPO administration.
AB  - Three intertwined issues--effectiveness, dosage, and route of administration-
      dominate discussion about recombinant human erythropoietin (rHuEPO). The major
      biological effect of rHuEPO is to regulate the number of committed erythroid
      precursors and to cause them to mature into erythrocytes. The constant presence
      of rHuEPO is critical to the sustenance, multiplication, and differentiation of
      committed erythroid progenitors that otherwise undergo apoptosis and die before
      they reach maturity. The route for rHuEPO administration influences the plasma
      concentration-time profiles. The erythropoietic response is not dependent on the
      peak concentration of rHuEPO achieved but on the duration of time that rHuEPO
      levels are maintained above a critical concentration. High levels immediately
      after intravenous doses are unnecessary to either induce or to sustain
      erythropoiesis. During the period of relative rHuEPO deficiency that invariably
      follows intravenous administration, committed but still rHuEPO-dependent cells
      undergo apoptosis and die in the bone marrow. The subcutaneous route sustains
      rHuEPO levels above basal levels in the interdialytic period, prevents death of
      rHuEPO-dependent cells, and results in more efficient and more sustained
      erythropoiesis. Areas under active investigation include modifications of the
      parent hormone and novel delivery systems that decrease elimination and maximize
      the residence time of rHuEPO in the circulation.

PMID- 10928338
TI  - Vascular effects of erythropoietin and anemia correction.
AB  - Since its introduction for clinical use a decade ago, recombinant human
      erythropoietin (rHuEPO) has revolutionized the management of the anemia of end
      stage renal disease. Soon after its release, it became evident that the
      biological targets of rHuEPO were not limited to the erythroid progenitor cells.
      Instead, numerous clinical and laboratory studies have shown the modulatory
      action of rHuEPO on a wide array of cell types and organ systems. The present
      article is intended to provide an overview of the modulatory actions of rHuEPO on
      the production and action of vasoregulatory factors and its direct and indirect
      effects on vascular function and structure.

PMID- 10928340
TI  - Novel erythropoiesis stimulating protein.
AB  - Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue
      of recombinant human erythropoietin (rHuEPO) that stimulates erythropoiesis by
      the same mechanism as the native hormone. The addition of two extra carbohydrate
      chains, however, gives NESP greater metabolic stability in vivo, and its terminal
      half-life after IV administration is three-fold longer than for IV rHuEPO. This
      allows injections of both IV and SC NESP to be given less frequently, and indeed
      studies have shown that once-weekly, and even once every other week, dosing can
      maintain the hemoglobin concentration in patients treated for renal anemia. The
      optimum starting dose is 0.45 microg/kg once weekly via the IV and SC routes of
      administration. Adverse effects are very similar to those seen with rHuEPO, and
      no antibodies have been detected in over 1,500 patients exposed to NESP thus far.
      NESP therefore represents a triumph for drug synthesis by recombinant DNA
      technology, and we can look to the future of this new therapeutic agent with much
      hope and expectation.

PMID- 10928342
TI  - Three-dimensional reconstruction of the coronary artery wall by image fusion of
      intravascular ultrasound and bi-plane angiography.
AB  - BACKGROUND: Intravascular ultrasound (IVUS) is becoming increasingly accepted for
      assessing coronary anatomy. However, its utility in visualizing and quantifying
      coronary morphology has been limited by its 2D tomographic nature. This study
      presents a 3D reconstruction technique that accurately preserves 3D geometric
      information. METHODS AND RESULTS: Images obtained from manual IVUS pullbacks and
      continuous bi-plane angiography were fused, using angiography to reconstruct the
      transducer trajectory and aid in solving for the correct rotational orientation.
      A novel 3D active surface method automatically identified the luminal and medial
      adventitial borders which, when superimposed on the transducer trajectory, could
      be surface-rendered for visualization and morphometry. Segmentation agreed well
      with manual assessment, and 3D luminal shape matched that of angiography when
      projected to 2D. CONCLUSIONS: We conclude that this method provides an accurate
      reconstruction of the vessel's anatomy, which accounts for the true curvature of
      the vessel.

PMID- 10928341
TI  - The optimal target hemoglobin.
AB  - There is still controversy concerning the optimal target hemoglobin during
      treatment with recombinant human erythropoietin (rHuEPO). Some evidence suggests
      that hemoglobin concentrations higher than currently recommended lead to
      improvements in cognitive function, physical performance, and rehabilitation. At
      least in patients with advanced cardiac disease, however, one controlled trial
      failed to show a benefit from normalizing predialysis hemoglobin concentrations.
      In contrast, preliminary observations in three additional studies (albeit with
      limited statistical power) failed to show adverse cardiovascular effects from
      normalization of hemoglobin, but definite benefit with respect to quality of
      life, physical performance, and cardiac geometry. These observations are
      consistent with the notion that hemoglobin concentrations higher than those
      recommended by the National Kidney Foundation Dialysis Outcomes Quality
      Initiative Anemia Work Group are beneficial, at least in patients without
      advanced cardiac disease.

PMID- 10928343
TI  - Assessment of coronary compensatory enlargement by three-dimensional
      intravascular ultrasound.
AB  - Several techniques have been used to demonstrate that human arteries respond to
      atherosclerosis by increasing their total arterial area to prevent a decrease in
      blood flow. Three-dimensional reconstructions of coronary arteries can document
      this compensatory response accurately and specifically. Seven human coronary
      arteries were reconstructed using intravascular ultrasound and biplane
      angiography, and vessel geometries were quantified. In all seven vessels, as
      plaque area increased, overall vessel area increased (R = 0.986, 0.933, 0.984,
      0.678, 0.763, 0.963, and 0.830), but luminal cross-sectional area did not
      significantly decrease. Focal compensatory enlargement was identified in each
      vessel, and in some cases this response appeared to occur until the vessel was
      65% occluded. Luminal enlargement near the proximal ends was attributed to the
      natural taper of the vessel. The semi-automated, three-dimensional segmentation
      technique used in this study allows reproducible quantification, as there is no
      subjective manual tracing involved. Following the intravascular ultrasound
      transducer in time and space with biplane angiography allows for accurate
      reconstruction with or without automated pullback devices. Information on the
      rate of change of vessel measurements is also presented, which, when combined
      with visualization of accurate 3D geometry, provides a unique assessment of
      coronary compensatory enlargement. This reconstruction technique can be applied
      in a clinical environment with no major modification.

PMID- 10928344
TI  - Absolute value of the difference of Tl-201 uptake between redistribution and rest
      is a specific marker of myocardial viability.
AB  - Although Tl-201 rest redistribution SPECT is widely used to assess myocardial
      viability, there is no agreement on the best prognostic marker of left ventricle
      contraction improvement after revascularization. More recent data suggest that
      not only rest or redistribution uptake but also reverse redistribution patterns
      may serve to indicate the viability of myocardium. The aim of this study was to
      define criteria (which include reversibility and reverse redistribution) for
      viability testing and prediction of functional outcome in Tl-201 rest
      redistribution SPECT. Twenty-five patients with left ventricle dyssynergy were
      studied before and after revascularization with Tl-201 SPECT and
      echocardiography. Perfusion and contractility was assessed in a 16-segment model
      of the left ventricle. Out of 400 left ventricular segments, contraction
      disturbances of various degree of intensity (hypokinesis, akinesis and
      dyskinesis) were found by echocardiography in 107 segments. Revascularization was
      performed in 97 segments. In 57% of the segments, improvement of contraction was
      observed after PTCA or CABG. Perfusion was analysed in the segments between
      segments with and without contraction improvement. In discriminant analysis, only
      the modulus of difference between rest and redistribution study > or = 10% was
      the common parameter for hypo-, a- and dyskinetic segments to predict the
      functional recovery of left ventricle (LV) with the specificity of 93% and
      sensitivity of 78%. The modulus of segmental quantitative difference between
      redistribution and rest image is a new parameter adding specificity to Tl-201
      rest redistribution SPECT in prediction of recovery of left ventricle function.

PMID- 10928345
TI  - Adipose replacement and wall motion abnormalities in right ventricle arrhythmias:
      evaluation by MR imaging. Retrospective evaluation on 124 patients.
AB  - We reevaluated the magnetic resonance (MR) examinations of 38 healthy volunteers
      (control group, CG) and of 124 patients with RV arrhythmia with left bundle
      branch block (LBBB) morphology: 45 with episodes of RV sustained tachycardia and
      of polymorphic RV premature beats (RVST-PPB group); 36 with only RV outflow tract
      sustained or not sustained tachycardia (RVOTT group); 43 with RV monomorphic
      premature beats (RVMPB group). All the examinations were reevaluated in a blinded
      fashion for detecting myocardial adipose replacement (AR) and wall bulges or
      aneurysms. In RVST-PPB patients, no AR was observed in 9%; 1 RV region
      involvement, 0%; 2 regions, 4%; > or = 3 regions, 87%; left ventricle (LV), 15%.
      RVOTT patients: 28%, 53%, 14%, 5%, and 0% [corrected], respectively. RVMPB
      patients: 33%, 46%, 19%, 2%, and 0% [corrected], respectively. In CG, AR was
      observed in 11% (in RV outflow tract), RV bulges were detected in 75% [corrected]
      of RVST-PPB, 39% of RVOTT, and 14% of RVMPB patients, none of the CG; RV
      aneurysms in 33% of RVST-PPB patients, none of RVOTT patients, RVMBP patients,
      and CG. A significant difference among groups for RV and LV AR as well as RV
      bulges and aneurysms was found (p < 0.0001). In the direct comparisons,
      significant differences were found for: disease duration (RVST-PPB vs. RVMPB, p =
      0.0396); RV AR (all the patients groups vs. CG, RVST-PPB vs. RVOTT or RVMPB, p <
      0.0001); RV aneurysms (RVST-PPB vs. CG, RVST-PPB vs. RVOTT or RVMPB, p < 0.0002);
      bulges (all comparisons, p < 0.0174). AR is confirmed as a structural substrate
      in RV arrhythmias. Number and extension of MR abnormalities are correlated to
      different degrees of RV arrhythmias.

PMID- 10928347
TI  - Equity: how much at century's end?

PMID- 10928346
TI  - Constrictive pericarditis from an embolized hypodermic needle: radiographic, CT
      and MR imaging findings.
AB  - We present the radiographic, computed tomographic (CT), and magnetic resonance
      (MR) findings in a woman with constrictive pericarditis due to an embolized
      hypodermic needle. The chest films revealed pleural effusions but no foreign
      body. The CT showed pericardial thickening and a linear foreign body of metallic
      attenuation in the right ventricular apex, and MR imaging revealed a signal void
      with magnetic susceptibility artifact. This case illustrates the capabilities and
      limitations of CT and MR imaging in hypodermic needle-induced constrictive
      pericarditis.

PMID- 10928349
TI  - Plasmodium ovale infections detected by PCR assay in Lao PDR.
AB  - Plasmodium ovate infection was demonstrated in 5 out of 143 inhabitants in a
      village in Lao PDR by blood microscopy and PCR assay. Although the specimen
      confirmed to be positive for P. ovale by microscopical examination was only one,
      the target sequences in the 18S rRNA genes of malaria parasite detected in all of
      the five cases were consisted with those of P. ovale by the PCR assay. This is
      the first report concerning the presence of so many cases with P. ovale infection
      in Lao PDR.

PMID- 10928348
TI  - El Nino and associated outbreaks of severe malaria in highland populations in
      Irian Jaya, Indonesia: a review and epidemiological perspective.
AB  - Perennial malaria is a major public health problem for most coastal, lowland and
      foothill populations in Irian Jaya (western New Guinea), the largest and
      easternmost province of Indonesia. Malaria at higher elevations above 1,500 m is
      considered intermittent and highly unstable, providing a constant threat of
      epidemics. Beginning in late August 1997, a significant increase of unexplained
      deaths was reported from the central highland district of Jayawijaya. The
      alarming number of fatalities rapidly escalated into September, dropping off
      precipitously by late October. More than 550 deaths due to "drought-related"
      disease had been officially reported from the district during this 10-week
      period. The outbreaks occurred in extremely remote areas of steep mountainous
      terrain inhabited by primitive shifting agriculturist populations. Microscopical
      evidence and site survey data implicated malaria as the principal cause of the
      excess morbidity and mortality at elevations between approximately 1,000 and
      2,200 m. The dramatic increase in malaria and associated deaths was indirectly
      related to the prolonged and severe drought created by the prevailing 1997-98 El
      Nino Southern Oscillation (ENSO) affecting the Australasian region. Clinical
      cases of malaria were described as severe, due, in large part to the low level of
      naturally acquired immunity (NAI) in these highland populations and the
      predominance of Plasmodium falciparum infection. Disease may have been further
      exacerbated by the population's compromised nutritional status because of severe
      shortages of staple foods affected by the drought. Based on a retrospective
      investigation, an 'a posteriori' epidemiological explanation of the probable,
      interrelated causes of the epidemic is presented. Beginning in late July 1997,
      drought conditions resulted in numerous, transient pools of standing water along
      zones of steep gradient streams normally associated with fast-flowing water. This
      permitted sufficient and rapid increases in vector populations (Anopheles
      punctulatus complex) that either could sustain recently introduced or intensified
      local low-level malaria transmission. Moreover, water and food shortages
      contributed to increased demographic movement and exposure to high risk malaria
      endemic lowlands, thus increasing the prevalence of human infections and
      infectious reservoirs in those populations returning to the highlands. The
      eventual rapid drying and elimination of the vector larval habitats along stream
      beds, combined with mass antimalarial drug distribution are believed, in part, to
      be responsible for the rapid decline of severe malaria and related deaths. Area
      delimited and isolated focal outbreaks of malaria are recognized as occasional,
      periodic events in these highlands. This epidemic produced great concern because
      of the broad regionalized extent of the problem, the culmination of many
      independent outbreaks occurring during the same period that overwhelmed the local
      health care and control capabilities. We predict communicable disease outbreaks,
      including malaria, may likely increase in periodicity in the Irian Jaya highlands
      as socioeconomic development and population movements increase. This
      investigation further underscores the importance of malaria and its impact on
      presumed NAI deficient highland populations. Furthermore, the association of ENSO
      related climatic anomalies and heightened infectious disease transmission is
      illustrative of how rapidly changing local weather events can dramatically alter
      disease patterns. These circumstantial findings, albeit important, point to the
      urgent need for more definitive understanding of highland malaria dynamics, the
      development of a sustainable longitudinal surveillance system, and appropriate
      outbreak response capabilities for the highlands of Irian Jaya.

PMID- 10928350
TI  - Hidden Plasmodium falciparum infections.
AB  - Mixed infection of P. vivax and P. falciparum malaria frequently recorded in
      field survey. However mixed infection was frequently misdiagnosed as single
      infection due to low parasite density, difficult species identification and
      procedure error of microscopic examination. Our previous report showed high rates
      (32-33%) of P vivax infection following treatment of previously assumed to be
      only P. falciparum infection. In a study of 992 patients with initial
      presentation with P. falciparum, we found that 104 (10.5%) of patients had P.
      falciparum appearing during 28 days in the hospital (ranged 1-28 days) following
      chloroquine treatment for P. vivax. The potential for P. falciparum appearing
      following elimination of P. vivax must be considered in malaria treatment.

PMID- 10928351
TI  - A comparison of three malaria diagnostic tests, under field conditions in North
      west Thailand.
AB  - A hospital-based trial to compare the clinical diagnosis of malaria; microscopy,
      and a rapid diagnostic antigen capture detection dipstick (ParaSight-F) was
      conducted in North-west Thailand. 301 people who presented themselves at the
      hospital were selected. 204 (68%) were presumptively diagnosed as having malaria
      by the triage nurses; 64 (21.3%) were P. falciparum parasite positive, and 94
      (32%) tested positive for P. falciparum with the ParaSight-F test strips. There
      was no association between hemoglobin levels (<10g/dl and > or = 10g/dl) and
      malaria, and although there was a good statistical association between
      temperature and malaria the specificity, sensitivity and positive predictive
      values were all low, indicating that temperature alone is a poor indicator of the
      disease. Based on the microscopy results, we found that a presumptive clinical
      diagnosis dramatically over-diagnosed malaria, and similarly there were a large
      number of false positives using the ParaSight-F test. We believe that many of the
      patients had received some form of malaria treatment prior to presentation at the
      hospital, and that the high number of false positives are explained by persistent
      antigenemia and the possibility of there being sequestered parasites following
      incomplete chemotherapy.

PMID- 10928352
TI  - A highly sensitive, nested polymerase chain reaction based method using simple
      dna extraction to detect malaria sporozoites in mosquitos.
AB  - Dried Anopheles farauti mosquitos caught in Solomon Islands in 1990 were examined
      for malaria sporozoites by ELISA and nested polymerase chain reaction (PCR). Only
      heads and thoraces were used. Plasmodium genus-specific nested PCR amplifications
      were carried out on all samples. Of the 402 pools of mosquitos that were
      processed, 30 were positive for malaria. Nest 1 products of positive samples were
      subjected to further PCR amplifications with species-specific primers for P.
      falciparum and P. vivax. Twenty pools were positive for P. vivax by PCR while
      only 7 were positive by ELISA. For P. falciparum 2 pools were positive by both
      ELISA and PCR, and one of these was a pool which was positive for P. vivax by PCR
      and ELISA. Thus the sensitivity of PCR for P. vivax was 100% while the
      specificity was 96.7%. For P. falciparum the sensitivity and specificity were
      100%. The PCR technique is highly sensitive and can be used on dried mosquitos
      which makes it a valuable tool for determining sporozoite rates of mosquitos,
      even in remote areas.

PMID- 10928353
TI  - Mitochondrial oxygen consumption in asexual and sexual blood stages of the human
      malarial parasite, Plasmodium falciparum.
AB  - The two developmental stages of human malarial parasite Plasmodium falciparum,
      asexual and sexual blood stages, were continuously cultivated in vitro. Both
      asexual and sexual stages of the parasites were assayed for mitochondrial oxygen
      consumption by using a polarographic assay. The rate of oxygen consumption by
      both stages was found to be relatively low, and was not much different.
      Furthermore, the mitochondrial oxygen consumption by both stages was inhibited to
      various degrees by mammalian mitochondrial inhibitors that targeted each
      component of complexes I- IV of the respiratory system. The oxygen consumption by
      both stages was also affected by 5-fluoroorotate, a known inhibitor of enzyme
      dihydroorotate dehydrogenase of the pyrimidine pathway and by an antimalarial
      drug atovaquone that acted specifically on mitochondrial complex III of the
      parasite. Moreover, antimalarials primaquine and artemisinin had inhibitory
      effects on the oxygen consumption by both stages of the parasites. Our results
      suggest that P. falciparum in both developmental stages have functional
      mitochondria that operate a classical electron transport system, containing
      complexes I-IV, and linked to the pyrimidine biosynthetic pathway.

PMID- 10928354
TI  - Cytokines associated with pathology in the brain tissue of fatal malaria.
AB  - Cytoadherence of Plasmodium falciparum-infected erythrocytes to the brain
      microvascular endothelial cells is believed to be an important cause of
      circulatory blockage in cerebral malaria. Cytokines released during acute
      infection may activate brain endothelial cells leading to increased binding of
      infected erythrocytes in the brain and reduced cerebral blood flow. This effect
      may be direct and more potent with the tissue-localized cytokines in the brain.
      In order to establish this relationship, brain tissues of cerebral and
      noncerebral malaria were compared. The most prominent histopathologic changes in
      the brain included edema, neuronal degeneration, ring hemorrhage, and percentage
      of parasitized erythrocytes sequestration were observed in cerebral malaria.
      Immunohistochemical staining of the brain sections demonstrated that tissue
      localized TNF-alpha, IFN-gamma, IL-I1B, and IL-10 were associated with the
      histopathology. However, IL-4 was the only cytokine presented at moderate level
      in the brain tissue of noncerebral malaria which histopathology was the least. No
      tissue-localized cytokine was observed in the brain of P. vivax infection or of
      the car accident control cases.

PMID- 10928355
TI  - Geographic information system as a tool to study malaria receptivity in Nadiad
      Taluka, Kheda district, Gujarat, India.
AB  - Nadiad taluka, Kheda district, Gujarat State, India, comprising of 100 villages
      with unstable malaria and periodic epidemics, was selected for the study. Using
      topo sheets and satellite imageries thematic maps on water table, water quality,
      hydro-geomorphology, soil type, relief, irrigation channels, were prepared,
      overlaid and integrated sequentially using Arclnfo software. The composite map
      resulted in 13 stratification classes. Stratification classes 1-12 fell in non
      irrigated tracts and exhibited 95% matching of areas of high receptivity as
      revealed by geographical information systems (GIS) and annual malaria parasite
      incidence (API). Stratification class 13, an irrigated area, showed poor matching
      but the ground verification established low receptivity of the area. Thus the
      study resulted in complete reconciliation of cause and effect relationship as
      established as per GIS in explaining malaria epidemiology. In general, the study
      revealed that high malaria in villages of Nadiad is mainly due to high water
      table, soil type, irrigation and water quality. Based on local malaria
      transmission determinants, a revised malaria control strategy has been suggested.

PMID- 10928356
TI  - Highlights on the World Bank Loan Schistosomiasis Control Program in China (1991
      1998): a special focus on Hunan Province.
AB  - A region-wide sampling survey was conducted in 1995 in order to evaluate the
      current epidemiological status of schistosomiasis japonica in Hunan Province,
      China. A total of 45,590 humans and 3,726 domestic animals, from 52 villages,
      were examined parasitologically and/or serologically for current Schistosoma
      japonicum infections. In uncontrolled endemic areas (43 villages) the overall
      human prevalence of S. japonicum was 7.81% across the different geographical
      subtypes. The geometric mean intensity of infection was 17.71 eggs per gram (epg)
      among infected individuals and only 1.25 epg in the general population. The
      bovine prevalence, as determined by the hatching test, was 9.63% in the
      uncontrolled endemic villages. Only one sero-positive (by indirect
      hemagglutination assay) child was found among 1,072 children tested aged 10-14
      years in the 9 endemic villages under effective control. No infection was
      confirmed by the Kato-Katz thick smear stool examination. When the results of
      this survey were compared to those seen at baseline (1989) an overall reduction
      of 45.65% was seen in the human prevalence but no significant change was apparent
      in the lake-beach ecotype. Additionally, there was more than a 60% reduction in
      the prevalence among bovines over the same sampling period. The results
      demonstrate that the World Bank Loan Schistosomiasis Program was successful in
      achieving its most basic objectives for this province - to reduce human and
      bovine infections by 40%.

PMID- 10928357
TI  - Schistosoma japonicum in the pig: a new technique for estimation of intestinal
      tissue egg counts.
AB  - This study introduced a new method for estimating intestinal tissue Schistosoma
      japonicum egg counts, based on scraping of the mucosal layer of different
      sections of the intestines. Twenty-eight Danish Landrace/Yorkshire/Duroc
      crossbred pigs were divided into 3 groups of 15, 5 and 8 pigs, respectively. Pigs
      were fed either a high- or low- protein diet and were infected by an intra
      muscular or per-oral route of infection with doses of either 1,000, 1,500 or
      3,000 S. japonicum cercariae. The pigs were killed 9-11 weeks post infection. For
      all 28 pigs the intestines were divided into 3 sections: cecum, colon and rectum
      and the entire mucosa was scraped off the serosa of each section and homogenized.
      Subsequently, samples corresponding to 5 g homogenised mucosal tissue were
      digested and egg counts were determined and correlated to liver egg counts. In
      order to compare the relative distribution of eggs in the mucosa and the serosa,
      small intestinal wall subsamples formerly taken from each section from a subgroup
      of 5 pigs were homogenized and egg counts determined for both the mucosa and
      serosa. The number of eggs were significantly higher in the mucosa than in the
      serosa. Egg counts estimated from digestion of mucosa subsamples either over or
      underestimated egg counts based on scrapings of the entire mucosa when compared,
      reflecting the very patchy distribution of S. japonicum eggs in the intestinal
      wall. Correlating liver egg counts with the number of eggs based on scrapings
      from the entire mucosa from cecum, colon and rectum, respectively, significant
      correlations were found for 2 out of 3 groups of pigs. The present study revealed
      that estimating intestinal tissue egg counts based on scrapings of the entire
      mucosa is a reliable and convenient approach, nicely supporting the liver tissue
      digestion approach. In addition, a reduction of the processing time of intestinal
      tissue in general was achieved due to the very simple scraping technique.

PMID- 10928358
TI  - Cytopathogenicity of Acanthamoeba isolates on rat glial C6 cell line.
AB  - The pathogenicity of Acanthamoeba isolates from keratitis patients (the Hamburg
      isolate from Germany, H-1 and a Philippine isolate, IB-1-7) as well as an
      environmental isolate, W4 was assayed in vitro using rat glial C6 cell line.
      Results indicate that both live amebae and cell-free supenatants from H-1 and IB
      1-7 clones produced cytopathic effects (CPE) on rat glial C6 cells in a dose-and
      time-dependent fashion. A dose of 10(5) cells/ml induced death and moderate areas
      of destruction of individual cells after 48 hours of incubation. Results of both
      free zone capillary electrophoresis and sodium dodecyl sulphate polyacrylamide
      gel electrophoresis suggest the release of amebic products to the culture medium
      that could at least partially explain the observed cytopathogenicity after 48
      hours. Furthermore, results of SDS-PAGE indicate differences between the
      secretions of the isolates, with bands produced by the two ocular isolates that
      were not seen with the environmental isolates. That the secretions can produce a
      cytopathic effect (CPE) has been shown by the cytotoxicity assays using protein
      concentrations of the secretory products. Protein concentration of 0.30
      microg/microl of culture supenatants from H-1 and IB-1-7 clones produced similar
      effects on the cell monolayers after 2 hours of incubation. This concentration
      caused the highest % cell death as measured by both trypan blue exclusion (TBE)
      and 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl-tetrazolium bromide (MTT) assays.
      In contrast, using W4 clone, corresponding concentrations of both trophozoites
      and culture supernatant did not cause significant cell death and cellular
      disintegration.

PMID- 10928359
TI  - Antibodies to somatic L3 antigen not protective against Brugia malayi infection.
AB  - Western blot analysis of infective larvae (L3) antigen of Brugia malayi were
      performed on 200 sera from six groups of individuals: 36 samples from B. malayi
      microfilaremic individuals; 10 samples from individuals with elephantiasis; 50
      and 20 samples from amicrofilaremic individuals in a B. malayi endemic area with
      no anti-filarial IgG4 antibodies (towards microfilaria and adult worm antigens)
      and samples with high titres of the anti-filarial IgG4 antibodies respectively;
      50 samples from non-endemic normals and 34 samples from geohelminth-infected
      individuals. After protein transfer, PVDF membrane strips were successively
      incubated with blocking solution, human sera, monoclonal anti-human IgG4 antibody
      HRP and developed with luminol chemiluminescence substrate. 28/36 (78%), 1/10
      (10%) and 16/20(80%) of sera from individuals with microfilariae, elephantiasis
      and amicrofilaremic individuals with high titers of anti-filarial IgG4 antibodies
      respectively recognized L3 antigenic epitopes; the dominant and consistent
      antigenic bands were of approximately MW 43 kDa, 14 kDa, 15 kDa and 59 kDa. The
      rest of the sera were unreactive. This study showed that microfilaremics may or
      may not mount a notable antibody response to somatic L3 antigens, thus lending
      evidence that antibody response to this antigen is not protective against
      establishment of Brugia malayi infection.

PMID- 10928360
TI  - Cost effectiveness in the discrimination of leishmania species causing
      anthroponotic leishmaniases in Asia using selective enzymes.
AB  - In this study, an attempt was made to evaluate the usefulness of selective
      enzymes in the identification of Leishmania spp causing anthroponotic
      leishmaniasis in Asia, especially from a cost effectiveness point of view. For
      this purpose cellulose acetate electrophoresis was carried out to identify the
      Leishmania species of the Old World. After analyzing 11 enzymes 6PGDH was found
      to be the most polymorphic enzyme which could distinguish the WHO reference
      strains of the Leishmania species endemic in Asian countries like L.(L.) donovani
      (DD8), L. (L.) infantum (IPT-I), L.(L.) major (5ASKH), and L.(L.) tropica (K-27).
      Addition of another enzyme G6PDH improved the quality of diagnosis. Cost could be
      reduced manifold to discriminate the Asian Leishmania parasites by analyzing
      these two enzymes.

PMID- 10928361
TI  - Re-emergence of paragonimiasis in Kyushu, Japan.
AB  - During 1986-1998 we found 104 paragonimiasis cases, which were referred to our
      laboratory for immunodiagnosis or identification of parasite eggs in sputum or
      bronchoscopic aspirate smears, or in histopathological sections. A majority of
      patients were middle-aged males. Except for 2 cases of chronic occult infection
      in an unexpected site, 102 cases were assumed as having active infection.
      Abnormal findings in chest radiograms were noted over 80% of the patients, though
      about 20% of them were asymptomatic. Parasite egg detection rates in sputum or
      bronchoscopic aspirate smears were about 50%. About 80% of patients have
      eosinophilia and/or elevated serum IgE level. Paragonimiasis is a re-emerging
      public health issue in Kyushu, Japan.

PMID- 10928362
TI  - Epidemiology of human ancylostomiasis among rural villagers in Nanlin County
      (Zhongzhou village), Anhui Province, China: age-associated prevalence, intensity
      and hookworm species identification.
AB  - Hookworm infection has traditionally been highly endemic to Anhui Province,
      China. Zhongzhou village in southwestern Anhui was identified as an endemic focus
      of infection caused by the hookworm Ancylostoma duodenale. This species was found
      to predominate over Necator americanus in ratios ranging from 35:1 based on the
      recovery of third-stage infective larvae (L,) to 21:1 based on the recovery of
      adult hookworms after anthelmintic chemotherapy. The overall prevalence of
      Ancylostoma infection in Zhongzhou was 33.2% with a greater prevalence among
      males. Unlike the age-associated prevalence patterns for N. americanus in Hainan
      and other southern Chinese provinces that show increasing prevalence with age and
      the highest prevalence among the elderly, the age-associated prevalence for A.
      duodenale in Zhongzhou exhibited a peak in middle-aged adults with subsequent
      decline. The age-associated intensity pattern exhibited a similar trend although
      the most of the hookworm infections were light or moderate infections as defined
      by quantitative egg counts.

PMID- 10928363
TI  - The first report on human cases serologically diagnosed as Japanese encephalitis
      in Indonesia.
AB  - Although Japanese encephalitis (JE) virus was isolated from mosquitos in 1974,
      human JE cases have never been reported in Indonesia in spite of the prevalence
      of anti-JE antibodies among human and pig populations as well as abundant JE
      vector mosquitos. In this report, we describe serological diagnosis of JE cases
      in Bali. Indonesia. using IgM-capture ELISA both on serum and cerebrospinal fluid
      (CSF) of the patients. In the first series of our investigation (Series 1), we
      examined serum specimens from 12 patients with clinical diagnosis of viral
      encephalitis, meningitis or dengue hemorrhagic fever (DHF), and found 2 possible
      JE cases. In the next series (Series 2), we examined both serum and CSF from
      encephalitis patients and gave laboratory diagnosis of JE. One of them was
      suspected to have concomitant or recent infection with dengue virus, probably
      type 3. These results strongly indicated that JE has been prevalent in Bali,
      Indonesia.

PMID- 10928364
TI  - Comparison between RT-PCR and rapid agglutination test for diagnosis of human
      rotavirus infection.
AB  - Rotavirus represents the major cause of dehydrating diarrhea among infants and
      young children on worldwide scale and has recently become the target of research
      aimed at developing a vaccine. To that end, screening tests of clinical specimens
      ought to provide high sensitivity and specificity. Hence, in order to achieve
      that aim we compared a commercially available latex agglutination (LA) kit with
      reverse transcription polymerase chain reaction (RT-PCR) using primers amplifying
      the gene for the major neutralization antigen in 71 stool samples of children
      with acute gastroenteritis during November 1998-April 1999. Based on accuracy
      (76.05%), specificity (86.8%) and sensitivity (63.6%) determined for LA with RT
      PCR serving as the gold standard, we recommend LA for field studies where speed
      and simplicity are crucial. Yet, for the purpose of further studies as to
      epidemiology and vaccine trials RT-PCR with its higher specificity and
      sensitivity will be required.

PMID- 10928365
TI  - Quantitation of T lymphocyte subsets helps to distinguish dengue hemorrhagic
      fever from classic dengue fever during the acute febrile stage.
AB  - Activation of immunoregulatory T lymphocyte subsets has been observed in dengue
      viral infection, being more evident in dengue hemorrhagic fever (DHF) than in
      classical dengue fever (DF). There are, however, as yet no well-defined host
      markers to determine which patients with dengue viral infection will develop
      severe complications during the acute febrile stage of the disease. A study was
      performed to compare the cellular immune status in DHF, DF and non-dengue viral
      infections (NDF) in order to determine the value of these parameters in
      distinguishing DHF from classic DF and other viral infections during the acute
      febrile stage of the disease. This study involved 109 febrile patients admitted
      because of suspected DHF. Fifty patients were serologically confirmed cases of
      dengue infection, of which 25 had grade 1 or 2 DHF. There was a reduction in
      total T (CD3), CD4 and CD8 cells in DHF and demonstrated that a low level of CD3,
      CD4, CD8 and CD5 cells discriminated DHF from DF patients during the febrile
      stage of the illness. In contrast, B (CD19) cells and natural killer (NK) cells
      did not appear to be discriminatory in this study. Receiver operating
      characteristic (ROC) curve analysis showed that a combination of CD3 cell of < or
      = 45% and CD5 cell of < or = 55% was the best marker to identify DHF patients
      (sensitivity = 84% and specificity = 52% for CD3 cell of < or = 45%; sensitivity
      = 92% and specificity = 71% for CD5 cell of < or = 55%). CD4 cell of < or = 25%
      and CD8 cell < or = 30% were equally good in discriminating DHF from DF patients.
      On the other hand, the ROC curves indicated no clear difference between the
      immunoregulatory cell counts in DF from NDF Lymphopenia, atypical lymphocytosis
      and thrombocytopenia were significantly more evident in dengue compared to non
      dengue infection but did not appear to be discriminatory among DHF and DF
      patients. The reduction in CD3, CD4, CD8, CD5 cells correlated with the degree of
      thrombocytopenia in DHF (p < 0.05) which suggests that these cells probably
      participate in a common pathogenetic mechanism.

PMID- 10928366
TI  - B cells are the principal circulating mononuclear cells infected by dengue virus.
AB  - Although dengue virus infects a variety of cells in vitro, little is known about
      cell types infected in vivo. Since blood is a readily accessible tissue, we chose
      to determine which circulating blood cells are infected by dengue viruses. We
      collected blood mononuclear cells from acutely ill dengue patients and separated
      the cells by flow cytometry into subsets for virus isolation. Cells were sorted
      into groups corresponding to the cluster designations CD3, CD14, CD16 and CD20.
      Virus was isolated from sorted groups by inoculation into Toxorhynchites
      splendens mosquitos. The majority of the virus was recovered from the CD20 or B
      cell positive subset. Little virus was isolated from monocytes, NK cells or T
      cells. Virus was isolated from B cells regardless of the age or sex of the
      patient, virus serotype isolated, or the patient's history of dengue virus
      infection. The location of cell associated virus was determined by proteolytic
      digestion of surface virus. There was an equal distribution of virus between the
      intracellular compartment and the surface of B cells. The intracellular
      localization of virus was confirmed by immunocytochemistry. Since this study
      focused on circulating cells, no inferences were made regarding infection of
      cells in solid tissues.

PMID- 10928367
TI  - Infection of dengue 2 virus strains isolated from patients exhibiting different
      disease severities to human peripheral blood leukocytes and production of
      cytokines in the infected culture supernatant.
AB  - Three strains of type 2 dengue virus (DV-2), which had been isolated from
      patients exhibiting different disease severity, were inoculated to primary
      culture of human peripheral blood leukocytes from 3 healthy donors. The
      percentage of dengue antigen positive cells was highest for the strain isolated
      from a case of dengue shock syndrome, followed by the strain isolated from a case
      of dengue hemorrhagic fever, and lowest for the strain isolated from a mild case
      of dengue fever (DF). Generally, similar trend was observed for the amount of
      some cytokines released into infected culture supernatant, such as interleukin 6,
      and tumor necrosis factor-alpha. However, such a trend was not observed for
      interleukin 1 beta.

PMID- 10928368
TI  - A clinical study of the patients with dengue hemorrhagic fever during the
      epidemic of 1996 at Lucknow, India.
AB  - This paper describes the clinical findings in 206 patients with dengue fever (DF)
      or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow.
      The age group affected most was 11 to 30 years and 21% of the patients were less
      than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all
      the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin
      rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria
      was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%,
      being associated with mild jaundice in one patient, and splenomegaly in 2% of the
      patients. Involvement of the heart and lungs was seen in one patient each and no
      case with encephalitis was recorded. Hemorrhages from various sites were observed
      in 54% patients and 17 patients had profound shock. The commonest bleeding site
      was gums. Profound shock was preceded by various warning signs, the commonest
      being sudden hypotension. Among the patients with profound shock the mortality
      was 47% while the overall fatality rate was 3.8%. A number of the risk factors
      existed for a long time in this part of the world, but what precipitated the
      present epidemic at this time, is not known.

PMID- 10928369
TI  - Coinfections with hepatitis g and/or c virus in hepatitis B-related chronic liver
      disease.
AB  - Concurrent infections with HGV and/or HCV (HGV/HCV) were investigated in 196
      patients with HBV-related chronic liver disease (115 chronic hepatitis, 31 liver
      cirrhosis, 50 hepatocellular carcinoma), and in 100 HBsAg carriers. Coinfections
      were detected in 18 (9.2%) patients with HGV (10) or HCV (5) or both agents (3),
      but in none of the HBsAg carriers. Patients with coinfection were more frequently
      exposed to blood transfusions (55.6% vs 5.6%) and also were more commonly anti
      HBe positive. Serum levels of HBV-DNA were lower in patients with HCV coinfection
      than in those coinfected with HGV. Interferon was administered to 39 patients
      with chronic active hepatitis including 7 patients with HGV/HCV coinfection.
      Sustained clearance of HBV-DNA was observed in 10 (25.6%) patients who were
      solely infected with HBV. These patients were significantly younger and had much
      lower histological scores than non-responders. Patients with HCV coinfection had
      significantly higher pre-treatment histological scores than those without HCV.
      After interferon treatment, a significant reduction in histological scores was
      observed in all patients except those coinfected with HGV/HCV. None of the 7
      patients with coinfection had sustained clearance of HBV-DNA or HCV-RNA, and only
      one had cleared HGV-RNA. These results suggest that parenteral exposure is a risk
      factor for HGV/HCV coinfection in chronic HBV infection. HGV infection shows no
      significant impact on chronic HBV infection. HCV coinfection appears to inhibit
      HBV replication, but causes more severe chronic hepatitis and increases
      resistance to interferon therapy.

PMID- 10928370
TI  - Prevalence of core promotor and precore mutants of hepatitis B virus in thailand
      by RFLP and sequencing.
AB  - Hepatitis B virus has been known to frequently undergo mutations of its genome at
      various sites, mostly due to it employing a reverse transcriptase devoid of
      proofreading capacity in the course of its replication. The purpose of the
      present study has been to screen 257 HBsAg-positive chronic liver disease
      patients, more specifically 78 cases chosen at random out of those negative for
      HBeAg and 33 of the HBeAg-positive cases serving as controls for three discreet
      point mutations in the precore/core region of hepatitis B virus. To that end, HBV
      DNA extracted from sera was amplified by polymerase chain reaction (PCR) using
      semi-nested primers and subsequently subjected to restriction fragment length
      polymorphism (RFLP) analysis, 36 HBeAg-negative versus 30 HBeAg-positive sera,
      respectively, as well as to direct sequencing in some samples randomly selected
      to corroborate the RFLP results. Our results showed double mutations at positions
      1762 and 1764 of the core promoter in between 25/36 (69.4%) and 19/25 (76%) of
      the sera tested, a missense mutation of the start codon in between 8/36 (22.2%),
      and 5/25 (20%) and a mutation turning codon 1896 into a stop codon in between
      9/36 (25%) and 6/25 (24%) determined by RFLP and sequencing, respectively. These
      data indicate the double mutation at positions 1762 and 1764 to be the most
      prevalent among HBeAg-negative chronic hepatitis patients in Thailand whereas, in
      contrast to reports from other Asian countries, the mutation at nucleotide 1896
      occurred in a mere 25%, while on the other hand the mutation abolishing the start
      of protein synthesis was observed to occur at a higher frequency than determined
      in several other geographical areas.

PMID- 10928371
TI  - Epidemiology of arabinose assimilation in burkholderia pseudomallei isolated from
      patients and soil in Thailand.
AB  - Burkholderia pseudomallei is an environmental saprophyte that has been isolated
      widely from soil in Southeast Asia and the relationship between environmental
      contamination and clinical melioidosis has been established. It has been shown
      that the arabinose assimilation property of B. pseudonrallei is probably one of
      the determinants indicating virulence of this organism. Therefore, the
      distribution of arabinose assimilation biotypes of B. pseudomallei collected from
      four geographic regions of Thailand was studied in order to determine an
      association between arabinose assimilation of B. pseudomallei and the uneven
      distribution of melioidosis found among these four areas. A total of 830 isolates
      of B. pseudomallei (412 patient isolates and 418 soil isolates) collected from
      the patients and soil in four regions of Thailand in 1997 were tested for an
      ability to grow on a minimal agar medium supplemented with L-arabinose. All
      patient isolates except one could not utilise arabinose (Ara-). For 418 soil
      isolates, 232 (55.5%) isolates were identified as Ara type. They comprised 180
      (62.5%), 36 (46.8%), 6 (35.3%) and 10 (27.8%) isolates derived from northeastern,
      southern, northern and central regions respectively. The ratios of Ara- to Ara,
      were 1.7, 0.9. 0.5 and 0.4 among isolates collected from northeastern, southern,
      northern and central regions respectively. The prevalence of Ara- in soil
      isolates in northeast is significantly higher than those in other regions. This
      observation suggests that in addition to the presence of B. pseudomallei in soil
      which is one of the factors contributing to a burden of melioidosis in
      northeastern Thailand, the distribution of more virulent biotype (Ara-) soil
      isolates is a factor contributing to a high prevalence of melioidosis in
      northeastern Thailand as well.

PMID- 10928372
TI  - Genotypic and phenotypic relationship in Burkholderia pseudomallei indicates
      colonization with closely related isolates.
AB  - Seven isolates of Burkholderia pseudomallei from cases of melioidosis in human (2
      isolates) and animal (2 isolates), cat (one isolate) and from soil samples (2
      isolates) were examined for in vitro sensitivity to 14 antimicrobial agents and
      for presence of plasmid DNA. Randomly amplified polymorphic DNA (RAPD) analysis
      was used to type the isolates, using two arbitrary primers. All isolates were
      sensitive to chloramphenicol, kanamycin, carbenicillin, rifampicin, enrofloxacin,
      tetracycline and sulfamethoxazole-trimethoprim. No plasmid was detected in all
      the isolates tested. RADP fingerprinting demonstrated genomic relationship
      between isolates, which provides an effective method to study the epidemiology of
      the isolates examined.

PMID- 10928373
TI  - Comparison of the efficacy of ceftibuten and norfloxacin in the treatment of
      acute gastrointestinal infection in children.
AB  - A prospective randomized study was conducted at an infectious disease hospital in
      Thailand. Ceftibuten was compared with norfloxacin, both given orally for five
      days for treatment of acute gastroenteritis in children. One hundred and seventy
      cases were included in the study. Eighty-eight cases were treated with ceftibuten
      and eighty-two cases with norfloxacin. The baseline characteristics of the
      patients in both treatment groups were similar. The results showed that mean
      durations of diarrhea in the ceftibuten and norfloxacin groups were 2.48 days and
      2.29 days, respectively, but there was no statistically significant difference
      between the two groups (p > 0.05). There were Salmonella spp and Shigella spp
      isolated in both treatment groups and all were susceptible to both antibiotics.
      The mean durations of Salmonella diarrhea in the ceftibuten and norfloxacin
      groups were 2.7 and 2.2 days, respectively, while those of Shigella diarrhea were
      2.3 days and 2.0 days, respectively. There were no statistically significant
      differences in either comparison (p > 0.05). Neither complications nor clinical
      relapses were observed after both antibiotics' treatment.

PMID- 10928374
TI  - Bacterial contamination of bottle milk in infants under 6 months in Children's
      Hospital, Bangkok, Thailand.
AB  - The bacterial contamination of bottle milk samples obtained randomly from 500
      infants under 6 months of age who came to the Out-patient Department of
      Children's Hospital Bangkok was determined by collecting bottle milk samples
      prepared at home following interview of their caretakers after obtaining their
      consent. Bacterial contamination was found in 91.8% (459/500) of bottle milk
      samples. Among the positive samples, 82.8% (380/459) contained enteric bacteria,
      another 17.2% were unidentified bacteria. The dominant enteric bacteria isolated
      from bottle milk were Klebsiella spp (56.6%), Enterobacter spp (41.3%), Aeromonas
      spp (14.4%), E. coli (13.4 %) and Vibrio cholerae non 0-1 (1.8%). Isolated E.
      coli were further identified as enteropathogenic E. coli (7.8%, 4/51) and
      enterotoxigenic E. coli (3.9%, 2/51). About 74% of the contaminated bottle milk
      contained one type of bacteria, 23.7% had two types and 2.3 % had 3 or more types
      of bacteria. A level of bacterial contamination greater than the US government
      limited number (USGLN 2x10(4) CFU/ml) was found in 86.4% of total examined
      samples (432/500) [geometric mean (GM) of 2.9 x 10(6) CFU/ml]. About 66%
      (333/500) of bottle milk samples had coliforms greater than the USGLN (1 x l0(2)
      CFU/ml) with GM of 1.3 x 10(4) CFU/ml. Therefore, in the preparation of bottle
      milk, feeding practice should be emphasized in every setting of maternal-child
      health care and promotion of breast-feeding should be encouraged by the health
      personnel.

PMID- 10928375
TI  - Incidence of new Salmonella serovar (S. ratchaburi) in Thailand.
AB  - Eighteen strains of Salmonella group E from stool samples were confirmed as
      Salmonella new serovar. 3, 10 : Z35 : 1, 6 by Centre International des
      Salmonella, Institut Pasteur, Paris, WHO Collaborating Center for Salmonella,
      Atlanta, USA and Salmonella-Zentrale Hygienischen Institut, Hamburg, Germany. The
      name of this new serovar was proposed as S. ratchaburi according to the place of
      its first isolation in Ratchaburi province. The new serovar of Salmonella was
      sensitive to many antimicrobial agents except streptomycin and erythromycin.

PMID- 10928376
TI  - Ciprofloxacin resistanceamong community-derived methicillin-resistant
      Staphylococcus aureus (MRSA) strains.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) has been recognized as a
      nosocomial pathogen in Europe and North America for almost 3 decades. More
      recently it has emerged as a problem in long-term care facilities. However, It
      has been less frequently considered a pathogen in community-acquired infections,
      where it is most often seen in intravenous drug users. Consequently there has
      been very few studies, particularly in Bangladesh, documenting incidence of
      ciprofloxacin-resistance among MRSA in community patients. We tested clinical
      isolates from outdoor patients for ciprofloxacin resistance among MRSA strains,
      using in vitro susceptibility tests by standard disk diffusion technique. Results
      show significantly high incidence of ciprofloxacin resistance among MRSA isolates
      in these patients.

PMID- 10928377
TI  - Study of hematopoietic progenitor cells, hematological values and lymphocyte
      subsets in cord blood: application for cord blood transplantation.
AB  - Hematological values, lymphocyte subsets and hematopoietic progenitor cells from
      normal term cord blood samples were studied, compared with normal adult blood,
      and analysed to determine whether a single collection of cord blood is sufficient
      for transplantation in adults. The parameters were assayed by automatic cells
      counter, flow cytometry and semisolid cell culture. All of the hematological
      values except RBC and MCHC were higher than in normal adult blood. Sex had an
      influence on RBC, Hb, Hct, Plt and reticulocyte counts. For lymphocyte subsets,
      all of the absolute CD3+, CD4+, CD8+ counts and T helper: suppressor ratio were
      higher than those of adult blood. All of the hematopoietic progenitor cells in
      cord blood were also higher than in adult blood. The mean volume of cord blood
      for each collection was 80.75 +/- 4.81 ml and the mean numbers of nucleated
      cells, CFU-GM and CD34+ were 13.51 +/- 0.38 x 10(8) cells, 4.33 +/- 0.66 x 10(5)
      colonies and 42.65 +/- 7.00 x 10(5) cells respectively. This 80 ml of cord blood
      would contain sufficient marrow repopulating cells for a recipient weighing about
      20 kg. Recently developed technology, including ex vivo expansion may even permit
      transplants in adults.

PMID- 10928378
TI  - Serum erythropoietin levels in thalassemia major and intermedia.
AB  - Serum erythropoietin (EPO) levels were determined by enzyme linked immunosorbent
      assay (ELISA) in 61 thalassemic patients, consisting of 23 thalassemia major (TM)
      patients with multiple transfusion, 38 patients with thalassemia intermedia (TI).
      Thirty-two normal controls were also studied. The mean serum EPO levels were
      significantly higher in both groups with TM (165.96 +/- 17.31 mlU/ml) and TI
      (126.43 +/- 50.56 mlU/ml) compared with the control group (8.33 +/- 3.91 mlU/ml).
      The mean value of hematocrit (Hct) in the patients with TM (18.70 +/- 3.51%) was
      lower than those with TI (25.24 +/- 4.19 %) whereas the mean serum EPO level were
      significantly higher in TM than TI patients. An inverse correlation between the
      serum values of EPO and Hct was observed in both TI and TM patients, however this
      correlation was significant only in TI (r = -0.61, p<0.001). These data showed
      that serum EPO levels increased in all thalassemia patients despite repeated
      transfusion. Multiple transfusion may modulate the response of serum EPO to the
      degree of anemia, resulting in increased EPO levels and independent anemia in the
      TM patients.

PMID- 10928379
TI  - Morbidity and mortality patterns, health beliefs, and health risk factors of
      Karen highlanders of northwest Thailand.
AB  - Morbidity and mortality patterns, health care practices, and health care beliefs
      were assessed over three seasons in Pwo and Sgaw Karen preschool children living
      in the highlands of northwest Thailand. The sample consisted of all preschool
      children from 77 Pwo and 71 Sgaw households. Although the Pwo and Sgaw Karen
      residing in the highlands of northwest Thailand live in isolated villages in the
      same ecozone, utilize similar technologies, have similar access to health
      facilities, and maintain a certain level of sociocultural homogeneity through
      their identification as Karen, Pwo preschool children exhibit significantly
      higher levels of morbidity and mortality than their Sgaw counterparts. It is
      argued that these differences in morbidity and mortality are primarily the
      function of historical patterns which resulted in an earlier contact of the Sgaw
      with modem societies and particularly with an earlier exposure to western health
      care.

PMID- 10928380
TI  - Temporal variations in biting density and rhythm of Culex quinquefasciatus in tea
      agro-ecosystem of Assam, India.
AB  - Temporal changes in the biting density and host-seeking periodicity of Culex
      quinquefasciatus, the vector of bancroftian filariasis, were studied for two
      years in the tea agro-ecosystem of Assam, India. Average biting density of the
      vector varied from 0.8/hour in December to 13.3/hour in March. Minimum
      temperature was found to have a limiting effect on the biting density of the
      vector mosquitos. Multiple regression analysis showed that the rainfall and
      minimum temperature were significant factors influencing biting density of this
      vector mosquito. The biting rhythm of Cx. quinquefasciatus was found to be
      nocturnal with two distinct peak periods of biting activity. The first peak was
      around 19.00 to 20.00 hours and the second peak period was around 22.00 to 23.00
      hours. Biting activity however was seen throughout the night with declining trend
      as the night proceeded.

PMID- 10928381
TI  - PET imaging in oncology.
AB  - The role of positron emission tomography (PET) during the past decade has evolved
      rapidly from a pure research tool to a methodology of enormous clinical
      potential. Perhaps the most striking development is the use of PET in oncology.
      PET imaging is approved in the United States for lung, lymphoma, colon, and
      melanoma cancer imaging. Data are accumulating rapidly to attest the efficacy of
      Fluorine-18 fluorodeoxyglucose (FDG) imaging in a wide variety of malignant
      tumors with sensitivities and specificities often in the high 90s. FDG uptake has
      been shown in tumors of the head and neck, ovary, breast, musculoskeletal system,
      and neuroendocrine system as well. The major role of PET has emerged as a
      reliable method for evaluating and staging recurrent disease. But it also has an
      important role in differentiating benign and malignant primary tumors. This has
      been shown particularly well in the differential diagnosis of solitary lung
      nodules. Although FDG has emerged as the dominant radiopharmaceutical for PET
      imaging in oncology, numerous other compounds are being evaluated. It is likely
      that more specific and efficacious compounds will be introduced during the next
      decade. F-18, because of its highly favorable physical characteristics, is likely
      to become the technetium of PET imaging. The next decade will witness an
      explosive growth of PET technology in oncologic imaging.

PMID- 10928382
TI  - Radioimmunoimaging and radioimmunotherapy: will these be routine procedures?
AB  - Despite major progress made during the past 25 years in the genetic engineering
      and labeling of monoclonal antibodies (Mab) and in the understanding of the
      uptake and kinetics of radiolabeled Mab by normal and tumor tissues,
      immunoscintigraphy never succeeded in becoming a routine procedure, compared with
      a bone or gallium scan. The more and more generalized availability of positron
      emission tomography (PET) with Fluorine-18 fluorodeoxyglucose (FDG) for diagnosis
      and staging of malignant diseases will probably definitively seal the fate of
      radioimmunodiagnosis as it has been conceived up until now. With respect to the
      nonspecificity of deoxyglucose uptake by tumor cells, it is not to be excluded
      that antibodies, or more likely antibody fragments, labeled with positron
      emitters might be used for tissue characterization. The recent success of
      radioimmunotherapy, especially in B-cell malignancies, entitles us to expect that
      RIT will become part of standard therapy of patients with malignancies. In that
      case, immunoscintigraphy will be needed for treatment planning (patient selection
      and dosimetry). One might even speculate that the oncologists who are becoming
      familiar with nuclear medicine tracer techniques for pretreatment evaluation
      might be interested in extending them to distribution and kinetic studies of
      other cytotoxic drugs. The close cooperation between nuclear medicine
      specialists, oncologists, and hematologists is essential to make
      radioimmunotherapy a routine procedure.

PMID- 10928383
TI  - Radio-labeled receptor-binding peptides: a new class of radiopharmaceuticals.
AB  - Radio-labeled receptor-binding peptides have emerged as an important class of
      radiopharmaceuticals. In vertebrates, these peptides transmit their biological
      function by binding to their specific receptor on the target cell surface. This
      specific receptor-binding property is exploited when the radio-labeled peptide is
      used as a radiopharmaceutical. The high-binding affinity for its receptor
      facilitates retention of the peptide in receptor-expressing tissues, whereas its
      relatively small size facilitates rapid clearance from the blood and other
      nontarget tissues. Receptor-binding peptides labeled with gamma-emitters can be
      used to visualize receptor-positive cells in vivo. In addition, when labeled with
      beta- or alpha-emitters, these peptides can be used for peptide-receptor
      radionuclide therapy. Various receptors are overexpressed on particular tumor
      types, and peptides binding to these receptors can be used to visualize tumor
      lesions scintigraphically. Furthermore, peptides binding receptors on
      granulocytes can be used to image infectious and inflammatory foci, whereas
      peptides binding receptors on activated thrombocytes can be used for thrombus
      imaging. Here, the peptide analogs that are under development for these
      applications are reviewed.

PMID- 10928384
TI  - Trends in American nuclear medicine training: past, present, and future.
AB  - As soon as the capability to produce radioactive atoms was achieved in the 1930s,
      physician-scientists gravitated as apprentices toward important research centers,
      such as those at Berkeley, Washington University, and Massachusetts Institute of
      Technology (M.I.T.)/Massachusetts General Hospital. After World War II, Oak Ridge
      Associated Universities (ORAU) trained many of the founders of the specialty of
      nuclear medicine. The initial ORAU preparatory course lasted only 3 weeks. Over
      the 20 years after World War II, only 100 to 200 physicians had learned
      radioisotopic techniques and their clinical applications from their older
      preceptors. The founding of the conjoint American Board of Nuclear Medicine in
      1971 (cosponsored by the American Boards of Internal Medicine, Pathology, and
      Radiology) marked a new era in certifying the quality of graduates of a growing
      number of nuclear medicine residency programs. Future trends in nuclear medicine
      education include the following: greater availability of jobs for physicians with
      board certification in radiology and nuclear medicine; an increased emphasis on
      training in positron-emission tomography (PET); and recertification and
      documentation of maintenance of professional competence as certainties.

PMID- 10928385
TI  - How will we teach and practice nuclear medicine in the next decade in Europe?
AB  - In the next decade, nuclear medicine physicians in Europe will try to guarantee a
      more homogeneous level of training and education of their specialty throughout
      the continent. In routine nuclear medicine, they will focus more on the
      possibilities and availability of positron-emission tomography (PET) and on
      nuclear medicine therapy. Nuclear medicine physicians will be more active and
      interactive with students at the universities and will offer more lectures and
      more active training in the specialty. Nuclear medicine specialists will try to
      be even more interactive with clinicians and make their specialty open and better
      understandable for other disciplines. Nuclear medicine physicians will initiate
      more cost-benefit studies and more multicenter studies to prove that their
      procedures are evidence-based. They will communicate more intensively with
      industry for a better understanding of clinical problems and for development of
      new useful radiopharmaceuticals. They will promote their specialty in the public
      more intensively and will reasonably explain the risks and benefits of
      radionuclide examinations.

PMID- 10928386
TI  - The Society of Nuclear Medicine in the new millennium.
AB  - The Society of Nuclear Medicine (SNM), which was first organized in January 1954
      by 12 men at the Davenport Hotel in Spokane, WA, has evolved into an
      international educational organization. It has more than 15,000 members,
      including physicians, scientists, technologists, and industrialists. The SNM has
      embarked on a new strategic plan that will make it the premier educational and
      scientific organization representing the specialty of nuclear medicine. The role
      of the Society in the new millennium and its relationship with other
      international nuclear medicine societies continue to evolve. The opportunity for
      joint educational programs, interchange of ideas, research, an international
      journal, educational activities, and the sharing of professional experiences
      awaits the SNM and its members in the new millennium. The Society has also
      reached out to other organizations and physicians who are involved in the
      clinical practice of nuclear medicine to forge new alliances that will strengthen
      the specialty of nuclear medicine. These alliances will allow nuclear medicine
      physicians to speak with a unified voice when faced with regulatory and
      reimbursement issues and will help in advancing the research, education, and
      clinical mission of the SNM.

PMID- 10928387
TI  - Impact of European societies on nuclear medicine.
AB  - The development of nuclear medicine in Europe began in the late 1940s and early
      1950s. The supply of radionuclides was initially restricted, but slowly a number
      of hospital departments and universities gained access to these materials. From
      the beginning there was a strong international presence, and communication among
      scientists and doctors flourished rapidly. The need for national and later
      international nuclear medicine gatherings became apparent, and there soon emerged
      a number of prominent organizations. This article describes some of the historic
      developments that led to the formation of a single European Association of
      Nuclear Medicine-the EANM.

PMID- 10928388
TI  - Incidental finding of pancreatic calcification on bone scan.

PMID- 10928389
TI  - Technetium-99m-ethyl cysteinate dimer brain perfusion loss in pediatric postictal
      psychosis.

PMID- 10928390
TI  - Antiretroviral prescribing errors in hospitalized patients.
AB  - OBJECTIVE: To quantify error type and frequency and to identify factors
      associated with antiretroviral prescribing errors in hospitalized HIV-infected
      patients. DESIGN: Systematic evaluation of all medication prescribing errors
      involving antiretroviral medications between January 1, 1996, and October 31,
      1998. Each error was concurrently evaluated for the potential to result in
      adverse patient consequences. Each error was retrospectively evaluated by three
      pharmacists and assigned a "likely related factor." SETTING: A 631-bed tertiary
      care teaching hospital. PARTICIPANTS: All physicians prescribing antiretroviral
      medications during the study period and all staff pharmacists involved in the
      routine review of medication orders. MAIN OUTCOME MEASURES: Type and frequency of
      prescribing errors involving antiretrovirat medications and frequency of
      association of likely related factors to errors. RESULTS: A total of 108
      clinically significant prescribing errors involving antiretrovirals were detected
      during the 34-month study period. The most common errors were overdosing and
      underdosing. Overall, errors occurred in 5.8% of admitted patients prescribed
      antiretroviral medications. The rate of error increased from 2% of admissions in
      1996 to 12% of admissions in 1998. The most common likely related factors
      associated with errors were confusion/lack of familiarity regarding appropriate
      dosing frequency (30.3%) or dosage (25.5%), and confusion due to need for
      multiple dosage units per dose (13%). CONCLUSIONS: Hospitalized patients taking
      antiretrovirals are at risk for adverse outcomes due to prescribing errors. This
      risk has increased with the rising complexity of antiretroviral drug regimens. A
      limited number of factors are associated with a large proportion of
      antiretroviral prescribing errors. This information should be considered in the
      development of medication error prevention strategies necessary to prevent
      adverse patient outcomes resulting from such errors.

PMID- 10928391
TI  - Frequency of cutaneous reactions on rechallenge with nevirapine and delavirdine.
AB  - OBJECTIVE: To determine the frequency of cutaneous reactions in a group of HIV
      infected adults attending a public hospital HIV clinic who received nevirapine,
      delavirdine, or both, as well as the consequences of rechallenge with the same or
      alternative agent. DESIGN: The medical records of patients who had received
      either or both agents between March 1997 and July 1998 were reviewed, including
      69 patients who initially received nevirapine and 20 who initially received
      delavirdine. Gender, ethnicity, HIV status, and plasma HIV RNA concentrations
      were analyzed as risk factors for the development of rash. RESULTS: The overall
      incidence of rash attributed to the initial use of one of these drugs was 37.1%.
      While rash due to delavirdine occurred more often, the rash due to nevirapine was
      more severe and resulted in hospitalization more frequently. There was a trend
      toward a higher frequency of rash in Latinos and possibly in women, but HIV
      status, CD4+ cell counts, and plasma HIV RNA were not risk factors for the
      development of rash. Drug therapy was temporarily or permanently discontinued
      because of rash in 19 of 69 (28%) and in five of 20 (25%) patients initially
      receiving nevirapine or delavirdine, respectively. Rash recurred in six of eight
      (75%) patients rechallenged with the same agent, and in seven of 10 (70%) who
      were crossed over to the alternative agent because of rash. Fever, in the absence
      of any apparent cause, was a significant predictor for the development of rash in
      patients receiving nevirapine. CONCLUSIONS: There is probably little value in
      attempting to retreat patients with cutaneous reactions, even with the
      alternative agent, except in patients with limited treatment options.

PMID- 10928392
TI  - Documentation of clinical interventions by pharmacy faculty, residents, and
      students.
AB  - OBJECTIVE: To describe the influence of pharmacy faculty, residents, and students
      at a community hospital by documenting the number and types of interventions
      attributable to their involvement in patient-care activities. METHODS: Between
      September 1, 1997, and May 31, 1999, data were collected using a computerized
      documentation system to characterize the intervention type, significance, and
      value of services rendered by an education group composed of pharmacy faculty (n
      = 2), residents (n = 4), and students (n = 22). RESULTS: The number, nature, and
      outcome category for all interventions were documented using an existing
      computerized documentation system. The education group accounted for 13% (n =
      2,873) of total clinical activities documented (n = 21,817). The most common
      activities reported were discharge counseling/education (31%), consultation by
      physicians and therapeutic recommendations (15%), and route conversion (6%).
      Interventions documented by the education group were classified as medium or high
      significance 50% of the time. Sixteen percent ($172,655) of the estimated cost
      avoidance documented by the pharmacy department was attributed to the education
      group. CONCLUSIONS: This study demonstrates that educational activities by
      pharmacy faculty, residents, and students have a positive influence on patient
      care in a community hospital.

PMID- 10928393
TI  - Stability of dapsone in two oral liquid dosage forms.
AB  - OBJECTIVE: Dapsone use in pediatric patients is increasing; however, the
      currently available tablet dosage form cannot be used in young children. The
      objective of our study was to determine the stability of dapsone in two oral
      suspensions stored at two temperatures. METHODS: Commercially available dapsone
      tablets (25 mg) were used to prepare the suspensions: the first in simple syrup
      and water with citric acid, the second in 1:1 Ora Sweet:Ora Plus to yield a
      concentration of 2.0 mg/mL. The dosage forms were stored in 10 amber plastic
      prescription bottles. Five were stored at 25 degrees C and five at 4 degrees C.
      Three samples were taken from each of five bottles at 0, 7, 14, 28, 42, 56, 70,
      and 91 days (n = 15). Dapsone concentrations in each sample were measured in
      duplicate by a validated and stability-indicating HPLC method; the pH of each
      sample was also determined. The drug was considered stable if the mean
      concentration > or =90% of the original concentration. RESULTS: The mean
      concentrations of dapsone were >95% of the initial concentrations for 91 days at
      both 4 degrees C and 25 degrees C in each suspension. There was a slight
      darkening of the samples stored at 25 degrees C. CONCLUSIONS: Dapsone was stable
      in two suspensions prepared from commercially available tablets for at least
      three months at 4 degrees C and 25 degrees C.

PMID- 10928395
TI  - Cyclosporine-induced anaphylaxis.
AB  - OBJECTIVE: To describe a case of an anaphylactic reaction after first ingestion
      of oral cyclosporine capsules (Neoral). CASE SUMMARY: A 73-year-old white woman
      was admitted for the treatment of metastatic breast carcinoma with an
      experimental oral paclitaxel solution in combination with cyclosporine capsules.
      After ingestion of the cyclosporine capsules, the patient collapsed within one
      hour. She initially experienced severe hypotension and bradycardia. After a few
      minutes, she developed severe tachycardia, dyspnea, and decreased consciousness.
      Administration of epinephrine, dexamethasone, clemastine, oxygen, and gelofusine
      (succinylated gelatin 4% in NaCl 0.9%) infusion resulted in complete recovery
      after several hours. The planned oral paclitaxel administration was canceled.
      Intravenous paclitaxel was given the next day, preceded by standard premedication
      with dexamethasone, clemastine, and cimetidine, without complications.
      DISCUSSION: To our knowledge, this is the first report in the literature of an
      anaphylactic reaction after oral ingestion of cyclosporine capsules. Earlier
      reports of anaphylaxis concerned intravenous cyclosporine or oral solutions of
      cyclosporine (both Sandimmune). These anaphylactic reactions were considered to
      be due to the pharmaceutical vehicle Cremophor EL or related substances, which
      are well-known causes of anaphylaxis. The capsules used in this case contain the
      Cremophor EL-related polyoxyl 40 hydrogenated castor oil as a base; our patient's
      anaphylactic shock may have been due to this substance. CONCLUSIONS: In addition
      to earlier reports about anaphylactic reactions after administration of an
      intravenous or oral solution of cyclosporine, this case shows that anaphylactic
      shock can occur after ingestion of cyclosporine capsules.

PMID- 10928394
TI  - Granulocyte colony-stimulating factor use in cancer patients.
AB  - OBJECTIVE: To conduct a retrospective drug utilization evaluation comparing the
      use of granulocyte colony-stimulating factor (G-CSF) at a university medical
      center with the American Society of Clinical Oncology (ASCO) CSFs Practice
      Guidelines. METHODS: Patients who received G-CSF from June 1, 1996, to December
      31, 1996, were identified through the pharmacy computer system and the medical
      records were reviewed for a randomly selected sample of 26% of the 289 patients
      identified. Outpatient, inpatient, and electronic medical records were reviewed
      for the indication, dosage, day of initiation, day of discontinuation, and
      absolute neutrophil count (ANC) monitoring plan for each course of G-CSF; these
      records were subsequently compared with the ASCO guidelines. RESULTS: The use of
      G-CSF after chemotherapy was evaluated in 51 patients who received a total of 182
      courses of G-CSF. The goal of chemotherapy was curative in 61% of courses. Sixty
      five percent of G-CSF courses were prescribed for primary prophylaxis. Of these,
      74% followed chemotherapy in patients with an expected incidence of febrile
      neutropenia > or =40% or followed chemotherapy in patients with compromised
      marrow reserve secondary to extensive prior therapy or in patients older than 60
      years. Most of the G-CSF courses (75%) were rounded to the nearest vial size. The
      areas of greatest departure from the ASCO guidelines included aspects of
      initiation and discontinuation of G-CSF courses and inadequate documentation of
      ANC recovery. CONCLUSIONS: These results demonstrate a number of specific
      opportunities for oncology pharmacists to improve the use of G-CSF in patients
      receiving chemotherapy. Recommendations were made to the pharmacy and
      therapeutics committee and medical oncologists to improve compliance with the
      ASCO guidelines.

PMID- 10928396
TI  - Extended-release nifedipine bezoar identified one year after discontinuation.
AB  - OBJECTIVE: To report a case of tablet impaction of nifedipine extended-release
      tablets (Procardia XL) discovered one year after discontinuation of the drug in a
      patient with peptic stricture. DATA SOURCES: English-language references
      identified via a MEDLINE search from 1966 through September 1998 and
      bibliographic review of pertinent articles. DATA SYNTHESIS: Extended-release
      nifedipine has been associated with the formation of medication bezoars in case
      reports. Bezoars are concretions of undigested material within the
      gastrointestinal (GI) tract. Although they can occur throughout the GI tract,
      bezoars are most frequently located in the stomach and, rarely, in the duodenum.
      We report an unusual case of tablet impaction with a gastric outlet obstruction
      in the duodenal area discovered one year after the patient stopped taking
      extended-release nifedipine. CONCLUSIONS: Extended-release nifedipine is
      associated with tablet impaction, even long after discontinuing administration.
      Although rare, clinicians should be aware of this potential problem when
      prescribing extended-release medications to patients at risk, and should consider
      this possible etiology when refractory epigastric pain and weight loss occur.

PMID- 10928397
TI  - Olanzapine-induced glucose dysregulation.
AB  - OBJECTIVE: To report a patient who developed severe exacerbation of type 2
      diabetes mellitus after the initiation of olanzapine therapy. CASE SUMMARY: A 54
      year-old African-American woman developed severe glucose dysregulation 12 days
      after the initiation of olanzapine. Prior to starting olanzapine therapy, the
      patient's diabetes was controlled by diet modification with a glycosylated
      hemoglobin of 6.5%. During olanzapine therapy, blood glucose concentrations could
      not be regulated despite use of antidiabetic agents, insulin, and dietary
      interventions. The patient also gained a total of 13 kg. Two weeks after
      discontinuation of all antipsychotic medications (olanzapine, quetiapine), the
      patient's blood glucose concentrations became better regulated and remained
      better controlled until discharge. DISCUSSION: All atypical antipsychotics are
      associated with weight gain. Obesity is a well-documented risk factor for
      developing type 2 diabetes mellitus. Currently there are only six published
      reports that implicate olanzapine as being associated with glucose dysregulation.
      The exact cause of glucose dysregulation with olanzapine is unclear, but weight
      gain does not seem to be the sole etiology. It has been hypothesized that
      serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic
      beta-cells. This would then result in inappropriately low insulin secretion and,
      therefore, hyperglycemia. Based on the Naranjo probability scale, the likelihood
      that olanzapine caused the glucose dysregulation in our patient was possible.
      CONCLUSIONS: Although olanzapine has shown greater clinical efficacy and is
      associated with fewer extrapyramidal side effects than typical antipsychotics, it
      may produce exacerbation or new emergence of diabetes mellitus. Further
      examination of the incidence and etiology of glucose dysregulation after the
      initiation of olanzapine therapy is necessary.

PMID- 10928398
TI  - Skin discoloration with blue food coloring.
AB  - OBJECTIVE: To describe a pediatric patient who developed a clinical cyanotic
      appearance after receiving an excessive amount of blue food coloring. CASE
      SUMMARY: An 11-year-old white girl with cerebral palsy was admitted for
      unresolving aspiration pneumonia and dehydration. Antibiotics and intravenous
      fluids were administered. During the hospital course, enteral nutrition
      containing blue food coloring was also administered. Twelve hours after the start
      of enteral nutrition, the patient appeared cyanotic despite a regular respiratory
      rate and normal oxygen saturation. The pediatric code response team was called.
      Enteral nutrition was stopped and then restarted without blue food coloring. Over
      the next 24 hours, the cyanotic appearance resolved and no further complications
      developed. DISCUSSION: At our institution, blue food coloring is used with
      enteral nutrition for detecting aspiration of stomach contents. The dietary
      department supplies food coloring to each nursing unit in pint-sized medicine
      bottles. Nurses place an unstandardized amount of blue food coloring into each
      enteral nutrition bag. This child received an unspecified amount of FD&C Blue No.
      1 food coloring. No toxicity studies exist for acute or human ingestion, but the
      National Academy of Sciences lists 363 mg/d of FD&C Blue No. 1 as a safe level
      for humans. We estimated this child ingested 780-3,940 mg of dye over a 12-hour
      period. CONCLUSIONS: This is the first known report of an adverse effect from
      blue food coloring. To prevent similar occurrences within our institution, the
      blue food coloring for tube feedings will be dispensed by the pharmacy department
      in standardized units.

PMID- 10928399
TI  - Possible serotonin syndrome associated with buspirone added to fluoxetine.
AB  - OBJECTIVE: To report the development of a possible serotonin syndrome in a
      patient taking buspirone and fluoxetine. CASE SUMMARY: A 37-year-old white man
      taking fluoxetine 20 mg/d for generalized anxiety disorder developed confusion,
      diaphoresis, incoordination, diarrhea, and myoclonus after buspirone was added to
      the drug regimen. DISCUSSION: Serotonin syndrome is a potentially lethal
      condition of serotonin hyperstimulation, which may develop rapidly or over the
      course of several weeks. Symptoms of serotonin syndrome typically occur following
      additions or increases of serotonin-enhancing drugs. Although buspirone has
      variable effects on post- and presynaptic 5-HT1A receptors that may reduce the
      risk of serotonin syndrome when administered as a single agent, it may cause an
      adverse reaction when given with other serotonergic drugs. CONCLUSIONS: Symptoms
      consistent with serotonin syndrome may develop with the concurrent administration
      of buspirone and fluoxetine.

PMID- 10928400
TI  - Minocycline-induced pericardial effusion.
AB  - OBJECTIVE: To describe a reversible hypersensitivity reaction characterized by
      pericardial effusion and acute mixed liver injury in a woman treated with
      minocycline. CASE SUMMARY: A 39-year-old white woman developed dyspnea and chest
      pain with pericardial effusion on echocardiography approximately 20 days after
      starting minocycline treatment. Additional manifestations consisted of
      eosinophilia and liver injury. No lung, skin, or joint involvement was noted;
      antinuclear antibody testing was negative. DISCUSSION: Minocycline has been
      associated with rare but severe hypersensitivity reactions and autoimmune
      disorders, generally involving the lungs, skin, or joints. We observed a patient
      with an unusual minocycline-induced reaction with pericardial effusion and acute
      mixed liver injury. The number of spontaneously reported cases in national and
      international databases indicates that minocycline-induced pericardial effusion
      is very rare as a main clinical manifestation. CONCLUSIONS: Clinicians should be
      aware of the possibility of pericardial effusion without lung, skin, or joint
      involvement as an adverse effect of minocycline.

PMID- 10928401
TI  - Pharmacotherapy of type 2 diabetes mellitus.
AB  - OBJECTIVE: To review the drug treatments and some of the popular, nontraditional
      remedies now available for type 2 diabetes mellitus, as well as selected
      investigational agents; to describe each medication's place in the overall
      approach to treatment. DATA SOURCES: English-language journals, abstracts, review
      articles, and newspaper accounts. DATA SYNTHESIS: In the past five years, there
      has been tremendous progress in the pharmacotherapy of diabetes, particularly
      type 2 diabetes. Several new agents have entered the clinical arena, and many
      more are in the late stages of investigation leading to approval. Sulfonylureas
      stimulate the production and release of insulin; these drugs must be used in
      patients with an intact pancreas. The meglitinides are nonsulfonylurea agents
      that are also insulin secretagogues. Unlike the sulfonylureas, repaglinide
      appears to require the presence of glucose to close the adenosine triphosphate
      sensitive potassium channels and induce calcium influx. Metformin reduces hepatic
      glucose production in some patients and increases peripheral glucose utilization,
      but its use is hampered by a high percentage of adverse reactions. Disaccharidase
      inhibitors effectively compensate for the defective early-phase insulin release
      by slowing the production of sugars from carbohydrates. Thiazolidinediones appear
      to activate peroxisome proliferator-activated receptor gamma, which is involved
      in the metabolism of lipids. Short-acting insulin and the role of weight-loss
      agents are also discussed. CONCLUSIONS: The availability of new options for
      diabetes therapy provides a chance for successful therapy in a larger number of
      patients. However, it is important to consider how much true benefit these new
      forms of treatment will have on the diabetic community. The best choice for a
      patient remains controversial.

PMID- 10928402
TI  - Phenytoin and enteral feedings: does evidence support an interaction?
AB  - OBJECTIVE: To systematically review the reported interaction between oral dosage
      forms of phenytoin and enteral feeding formulations with respect to the evidence
      supporting or refuting its existence, proposed mechanism(s) underlying the
      interaction, and recommended interventions. DATA SOURCES: We conducted a MEDLINE
      search (1966-April 2000) for English-language articles on phenytoin-enteral
      feeding interactions; the search terms used were phenytoin, enteral feeding,
      and/or interaction, and/or in vitro. This search was supplemented by a
      bibliographic review of all relevant articles. STUDY SELECTION: Prospective,
      randomized, controlled studies; prospective, nonrandomized, controlled studies;
      prospective, nonrandomized, uncontrolled studies; retrospective studies; clinical
      experience reports; case reports; in vitro studies; and letters were evaluated
      for relevant information. DATA EXTRACTION: Data elements abstracted from these
      articles were study design, type (patients or healthy volunteers) and number of
      subjects involved, method of administration of phenytoin and enteral feeding,
      formulation of phenytoin, type of feeding (and whether it was continuous or
      interrupted), major findings, and proposed mechanisms of the interaction. DATA
      SYNTHESIS: Although four prospective, randomized, controlled trials in healthy
      human volunteers refute the existence of the interaction, there are numerous
      reports and studies showing dramatic decreases of serum phenytoin concentrations
      in patients when it is coadministered with enteral feeding formulations.
      Therefore, evidence supports the existence of this interaction in patients and in
      vitro studies, but not in healthy volunteers. Unfortunately, the exact mechanisms
      underlying this interaction remain unknown. Many methods have been devised to
      prevent and treat the interaction once it has occurred; however, a single,
      generally accepted, and practical intervention strategy is still lacking.
      CONCLUSIONS: The exact role of enteral feeding in this interaction is unclear due
      to the lack of prospective, randomized, controlled trials performed in patients.
      However, decreased serum phenytoin concentrations associated with enteral feeding
      may increase the risk of seizures. Clinicians should be aware of this potential
      drug-nutrient interaction and design a patient-specific care plan that includes
      consideration of the enteral feeding formulation and method of administration, as
      well as the phenytoin dosage form, schedule of administration, and monitoring.

PMID- 10928403
TI  - Understanding quality-adjusted life years and their application to
      pharmacoeconomic research.
AB  - OBJECTIVE: To provide a basic overview of quality-adjusted life years (QALYs) and
      their application in cost-effectiveness analysis (CEA), compare and contrast
      QALYs with other health-related quality-of-life (HRQOL) assessments, describe
      current controversies regarding QALYs, and provide comparisons between QALY
      instruments. METHODS: The literature regarding HRQOL and QALYs was reviewed and
      key issues are summarized. RESULTS: QALYs provide relative preferences of
      patients for different health states. They range from 0, representing death, to
      1.0, representing optimal health. QALYs are distinguished from other HRQOL
      assessments in that they provide a summary measurement that incorporates quantity
      of life in addition to HRQOL. When QALYs are used as the outcome measure in CEA,
      a cost per QALY is calculated. The Panel on Cost Effectiveness in Health and
      Medicine has recommended that QALYs be used as outcome measures in CEA; when
      QALYs are used in CEA, comparisons between treatments for different illnesses as
      well as within an illness are possible. The three most commonly used preference
      measurement techniques in determining QALYs are visual analog scales, time trade
      off, and standard gamble. Controversies regarding QALYs include which preference
      measurement technique is most appropriate, whether QALY assessments should be
      obtained from patients or the community, and how to address states, such as coma,
      that individuals sometimes assess as worse than death. QALY instruments can be
      compared regarding preference measurement technique, HRQOL domains assessed, ease
      of administration, validity, reliability, and sensitivity. CONCLUSIONS: When used
      appropriately, QALYs provide valuable outcome measures for pharmacoeconomic
      research.

PMID- 10928404
TI  - Controlled-release, pegylation, liposomal formulations: new mechanisms in the
      delivery of injectable drugs.
AB  - OBJECTIVE: To review recent developments in novel injectable drug delivery
      mechanisms and outline the advantages and disadvantages of each. DATA SOURCES: A
      MEDLINE (1995-January 2000) search using the terms polyethylene glycol,
      liposomes, polymers, polylactic acid, and controlled release was conducted.
      Additional references were identified by scanning bibliographies. STUDY SELECTION
      AND DATA EXTRACTION: All articles were considered for inclusion. Abstracts were
      included only if they were judged to add critical information not otherwise
      available in the medical literature. DATA SYNTHESIS: A number of systems that
      alter the delivery of injectable drugs have been developed in attempts to improve
      pharmacodynamic and pharmacokinetic properties of therapeutic agents. New drug
      delivery systems can be produced either through a change in formulation (e.g.,
      continuous-release products, liposomes) or an addition to the drug molecule
      (e.g., pegylation). Potential advantages of new delivery mechanisms include an
      increased or prolonged duration of pharmacologic activity, a decrease in adverse
      effects, and increased patient compliance and quality of life. Injectable
      continuous-release systems deliver drugs in a controlled, predetermined fashion
      and are particularly appropriate when it is important to avoid large fluctuations
      in plasma drug concentrations. Encapsulating a drug within a liposome can produce
      a prolonged half-life and a shift of distribution toward tissues with increased
      capillary permeability (e.g., tumors, infected tissue). Pegylation provides a
      method for modification of therapeutic proteins to minimize many of the
      limitations (e.g., poor stability, short half-life, immunogenicity) associated
      with these agents. CONCLUSIONS: Pegylation of therapeutic proteins is an
      established process with new applications. However, not all pegylated proteins
      are alike, and each requires optimization on a protein-by-protein basis to derive
      maximum clinical benefit. The language required to describe each pegylated
      therapeutic protein must be more precise to accurately distinguish each protein's
      differential pharmacologic properties.

PMID- 10928405
TI  - Acute profound thrombocytopenia following abciximab therapy.
AB  - OBJECTIVE: To report a case of acute, profound thrombocytopenia (APT), defined as
      an abrupt drop in platelet count to <20,000/mm3 that occurred within 24 hours of
      administration of an abciximab bolus, to summarize other abciximab-associated APT
      cases reported in the literature, to review the postulated mechanisms behind this
      reaction, and to emphasize the importance of periodically monitoring platelet
      counts after initiating abciximab therapy. DATA SOURCES: MEDLINE and Index
      Medicus searches restricted to English-language literature from 1993 through June
      1999 were conducted. MeSH headings included abciximab, ReoPro, thrombocytopenia,
      and glycoprotein IIb-IIIa (GP IIb-IIIa) inhibitors. References of the articles
      obtained were also reviewed. DATA EXTRACTION: Search and evaluation were focused
      on published case reports and reviews of abciximab-induced APT, as well as the
      incidence of thrombocytopenia from the drug compared with that from other GP IIb
      IIIa inhibitors. DATA SYNTHESIS: Platelet aggregation has been identified as the
      structural basis for coronary thrombosis. This may lead to ischemic complications
      during acute coronary syndromes or following coronary intervention procedures.
      The use of GP IIb-IIIa inhibitors such as abciximab as antiplatelet agents has
      been effective in reducing these ischemic complications. We summarize 15
      published cases of abciximab-associated APT gathered from data on 2,482 patients
      treated with the drug. Prior to suspecting abciximab, other potential causes of
      thrombocytopenia should be evaluated. It is important to monitor the platelet
      count at baseline, two hours after initiating abciximab, and 24 hours after
      initiation of therapy or prior to discharge, whichever comes first, to identify
      patients at risk for developing APT. If APT occurs and is left untreated, it can
      produce excessive hemorrhage and ischemia, potentially leading to death. Platelet
      transfusions have been more effective than immunoglobulin in the management of
      APT. CONCLUSIONS: Abciximab-induced APT has a low incidence of occurrence. If it
      does develop and is not recognized or treated promptly, it can lead to serious
      hemorrhagic complications. Consequently, monitoring the platelet count two hours
      after initiation of the infusion is essential. If APT develops, abciximab should
      be discontinued and a platelet transfusion should be considered.

PMID- 10928406
TI  - Soy protein in the management of hyperlipidemia.
AB  - OBJECTIVE: To review the effects of soy on blood lipids and to provide guidance
      on the clinical relevance of soy's health effects with respect to hyperlipidemia.
      DATA SOURCES: Clinical literature accessed through MEDLINE and EMBASE (1966
      November 1999). Key search terms included soy, isoflavone, phytoestrogen,
      cholesterol, and blood lipids. DATA SYNTHESIS: A review of studies evaluating the
      effects of soy protein on blood lipids was undertaken. Soy may be an alternative
      for patients seeking modest reductions in low-density lipoprotein cholesterol
      (<10%). CONCLUSIONS: Soy can improve blood lipid parameters in both
      normocholesterolemic and hypercholesterolemic subjects, although the use of soy
      alone may not allow patients with hyperlipidemia to achieve target lipid
      parameters, as indicated by the National Cholesterol Education Program. Further
      study is warranted for the use of soy in combination with traditional
      hyperlipidemic medications.

PMID- 10928407
TI  - Clindamycin in the treatment of streptococcal and staphylococcal toxic shock
      syndromes.
AB  - OBJECTIVE: To evaluate the utility of clindamycin in the treatment of
      streptococcal and staphylococcal toxic shock syndromes. DATA SOURCES: Biomedical
      literature was accessed through MEDLINE (1966-December 1999). Key terms included
      clindamycin, streptococcal toxic shock, and staphylococcal toxic shock. DATA
      SYNTHESIS: Streptococcal and staphylococcal toxic shock syndromes are associated
      with a high mortality rate. beta-Lactams have been considered the drug of choice
      for the treatment of these serious infections, with the occasional use of
      adjunctive clindamycin, although no clinical evidence has been published to
      support this latter regimen. An evaluation of the information to propose the
      usefulness of clindamycin was conducted. CONCLUSIONS: Experimental laboratory
      evidence suggests utility of the adjunctive use of clindamycin in streptococcal
      and staphylococcal infections complicated by toxin production. Research using
      animal models comparing clindamycin plus beta-lactams with beta-lactams alone for
      the treatment of these infections would be useful.

PMID- 10928408
TI  - Deja vu all over again: adverse reactions to nonnucleoside reverse transcriptase
      inhibitors.

PMID- 10928409
TI  - Women in pharmacy: twenty-five years of growth.
AB  - In the last 25 years, the number of women pharmacists has increased. Some of the
      predictions concerning the impact of these women on the profession of pharmacy
      have proven to be true. The issues presented in the predictions, a decline in
      manpower, a decrease in pharmacists' salaries, and a lack of leadership, are
      discussed. Pharmacy education and the increased number of women faculty members
      illustrate the changes that have occurred. These changes will have a positive
      impact on the pharmacy profession.

PMID- 10928410
TI  - Women in pharmacy: some predictions for women students and faculty.

PMID- 10928411
TI  - Women's role in pharmacy practice in the year 2000.

PMID- 10928412
TI  - Fluorouracil-induced aphasia.

PMID- 10928413
TI  - Pregnancy outcome in a woman exposed to continuous intrathecal baclofen infusion.

PMID- 10928414
TI  - Comment: prothrombin time monitoring devices.

PMID- 10928415
TI  - Progesterone as a neuroactive neurosteroid, with special reference to the effect
      of progesterone on myelination.
AB  - Some steroids are synthesized within the central and peripheral nervous system,
      mostly by glial cells. These are known as neurosteroids. In the brain, certain
      neurosteroids have been shown to act directly on the function of membrane
      receptors for neurotransmitters. For example, progesterone inhibits the neuronal
      nicotinic acetylcholine receptor, whereas its 3alpha,5alpha-reduced metabolite
      3alpha,5alpha-tetrahydroprogesterone (allopregnanolone) activates the gamma
      aminobutyric acid receptor complex A (GABA-R(A)). Besides these effects,
      neurosteroids also regulate important glial functions such as the synthesis of
      myelin proteins. Thus, in cultures of glial cells prepared from neonatal rat
      brain, progesterone increases the number of oligodendrocytes expressing the
      myelin basic protein (MBP) and the 2',3'-cyclic nucleotide-3'-phosphodiesterase
      (CNPase). An important role for neurosteroids in myelin repair has been
      demonstrated in the rodent sciatic nerve, where progesterone and its direct
      precursor pregnenolone are synthesized by Schwann cells. After cryolesion of the
      male mouse sciatic nerve, blocking the local synthesis or action of progesterone
      impairs remyelination of the regenerating axons, whereas administration of
      progesterone to the lesion site promotes the formation of new myelin sheaths.

PMID- 10928416
TI  - Progesterone, progestagens and the central nervous system.
AB  - Oestrogen, progestagens and androgens are able to modulate several brain
      functions. Receptors for gonadal steroids have been identified in several brain
      areas: amygdala, hippocampus, cortex, basal forebrain, cerebellum, locus
      coeruleus, midbrain rafe nuclei, glial cells, pituitary gland, hypothalamus and
      central grey matter. The mechanism of action of sex steroids at this level is
      similar to that observed in the peripheral target organs, including both genomic
      and non-genomic effects. The increased use of sex steroid hormone derivative
      therapies has lead to study of the biochemical and metabolic properties of the
      different progestin molecules available in hormonal therapies. In particular,
      experimental and clinical studies focused the attention of researchers on
      interactions between oestrogens and progestins in the neuroendocrine control of
      the brain functions and its clinical implications. Moreover, steroids are also
      synthesized de novo in the brain or may be derived from the conversion of blood
      borne precursors, suggesting that the brain is also a source of steroids, named
      neurosteroids. Neurosteroids exert non-classical rapid actions as allosteric
      agonists of gamma-aminobutyric acid receptor A (GABA(A)) and also modulate
      classic neurotransmitters in the brain. In addition, progesterone derivatives,
      e.g. pregnanolone, and 3alpha 5alpha-OH THP (allopregnanolone) are synthesized de
      novo by astrocytes and oligodendrocites starting from cholesterol. Physiological
      or pathological modifications of the synthesis and release of neurosteroids play
      a relevant role in the control of brain function.

PMID- 10928417
TI  - Effects of progesterone on sperm function: mechanisms of action.
AB  - Progesterone stimulates sperm functions, e.g. hyperactivation, acrosome reaction,
      binding to oocyte zona pellucida and penetration rate into the hamster oocyte.
      The physiological relevance of these effects has been shown using female genital
      tract fluids which modulate sperm function according to their progesterone
      content. Progesterone interacts with specific sperm binding sites that, unlike
      the classic nuclear receptors, are located on the plasma membrane of the
      spermatozoon. Binding studies have revealed the presence of two classes of
      progesterone receptors in the human spermatozoon, one class has an elevated
      affinity constant (nanomolar) and is specific for progesterone, whereas the other
      class has an affinity constant in the micromolar range and binds equally well
      other hydroxylated progesterone derivatives. Following exposure to progesterone,
      the main event is a rapid (within seconds) increase of the intracellular free
      calcium concentration, followed by a sustained rise lasting for several minutes
      (plateau phase). Both these calcium transients are dependent upon entry of
      extracellular calcium. The nature of the calcium channel that mediates the
      effects of progesterone is, currently, unknown. It has been postulated that it
      may be: (i) part of the progesterone receptor; (ii) voltage-dependent; or (iii)
      operated by second messengers following activation of the progesterone receptor.
      Progesterone also modulates sperm function by stimulating a trypsin-like
      proteolytic activity, the biosynthesis of polyamine (putrescine and spermidine),
      phospholipase A2 activity and protein tyrosine kinase activity in the sperm cell.
      Recent studies have shown that chloride ion efflux is vital for progesterone to
      promote the acrosome reaction. This effect is achieved by interaction with a
      sperm membrane receptor which resembles the neuronal GABA(A) receptor.
      Accordingly, GABA(A) receptors have been found in the spermatozoon plasma
      membrane and GABA stimulates hyperactivation and promotes the acrosome reaction.

PMID- 10928418
TI  - Progesterone inhibits in-vitro embryotoxic Th1 cytokine production to trophoblast
      in women with recurrent pregnancy loss.
AB  - A dichotomous T-helper 1 (Th1) versus T-helper 2 (Th2) cytokine response to
      trophoblast has been proposed to mediate reproductive failure and success,
      respectively. Progesterone has immunosuppressive properties. In this study,
      peripheral blood mononuclear cells from women with and without unexplained
      recurrent pregnancy loss who had and did not have evidence of embryotoxic, Th1
      immunity to trophoblast were cultured with progesterone (10(-5) mol/l) or
      interleukin (IL)-10 (1500 pg/ml) to determine whether these agents were capable
      of inhibiting embryotoxic, Th1 immunity to trophoblast. The effects of
      progesterone on Th2 cytokines and transforming growth factor (TGF)-beta secretion
      were also assessed. Progesterone was found to specifically block Th1 immunity to
      trophoblast, as was IL-10. Progesterone also appeared to upregulate TGF-beta
      secretion in response to trophoblast but had no effect on Th2 cytokine secretion.
      Our data suggest that assaying Th1 cytokines in supernatants of peripheral blood
      mononuclear cells cultured with a protein extract from trophoblast may identify
      individuals more likely to benefit from potentially immunosuppressive doses of
      progesterone. An appropriately designed clinical trial is needed to determine
      whether therapies modifying Th1 cytokine secretion in response to trophoblast are
      useful in the clinical management of recurrent pregnancy loss in women producing
      these cytokines in response to reproductive antigen stimulation.

PMID- 10928419
TI  - The relative effects of progesterone and progestins in hormone replacement
      therapy.
AB  - Hormone replacement therapy (HRT) was initially given to protect women against
      osteoporosis and alleviate menopausal symptoms, such as hot flashes, depression,
      sleep disturbances, and vaginal dryness. In view of the understanding of
      oestrogen deficiency as a major trigger for the acceleration of cardiovascular
      risk after menopause, HRT may also be proposed as a substantial beneficial
      cardioprotective agent. Progestins, which may be added to oestrogen in combined
      HRT to reduce the risk of uterine malignancy, have a number of potential adverse
      effects on the cardiovascular system which could even attenuate the benefit of
      unopposed oestrogen replacement therapy in post-menopausal women.

PMID- 10928420
TI  - Progestin regulation of human endometrial function.
AB  - A well-orchestrated sequence of events enables the human endometrium to become
      receptive to embryo implantation during a defined period in the menstrual cycle.
      Ovarian steroids, oestradiol and progesterone, regulate many of these functions
      in a highly co-ordinated manner. There are no experimental systems for critically
      examining the regulation of endometrial functions by steroid hormones, especially
      those responses restricted to the epithelium. Using an experimental xenograft
      model where the steroid responses of normal endometrium could be predictably
      recapitulated, the role of progesterone in the regulation of alpha crystallin B
      in the glandular epithelial cells of human endometrium was established.

PMID- 10928421
TI  - Uterine contractility during the menstrual cycle.
AB  - The non-pregnant uterus shows different patterns of contractility during the
      menstrual cycle. A renewed interest in uterine contractility has resulted from
      reports of non-invasive ultrasound (US) based studies. To clarify the changes in
      uterine contractility occurring throughout the menstrual cycle, we prospectively
      studied uterine contractions (UC) at six representative stages with US and
      intrauterine pressure (IUP) based approaches in 30 cycling volunteers. Results
      showed UC frequency could be measured by either US or IUP. UC amplitude and
      resting pressure tone could only be assessed by IUP. Conversely, direction of UC
      displacement could only be assessed by US. UC frequency increased at mid-cycle
      and decreased throughout the luteal phase suggesting oestradiol and progesterone
      exert positive and negative actions on uterine contractility, respectively. UC
      amplitude increased throughout the menstrual cycle to maximum values in the late
      luteal phase. Retrograde UC were most frequent at mid-cycle and convergent
      ('opposing') UC predominated during the luteal phase. While the former pattern
      ensures sperm transport, the latter may facilitate embryo implantation. In
      conclusion, UC changes throughout the menstrual cycle assessed by US and IUP
      emphasize the hormonal dependence of uterine contractility. Although UC patterns
      favouring sperm transport appear regulated by oestradiol, uterine quiescence and
      the dominance of convergent UC prevailing at the time of implantation are linked
      to progesterone. These data will serve to identify and treat possible dyskinetic
      changes in uterine contractility, particularly in women suffering from
      infertility, endometriosis, and dysmenorrhea.

PMID- 10928422
TI  - Hormonal influence on the uterine contractility during ovarian stimulation.
AB  - High-frequency uterine contractions (UC) at the time of embryo transfer have been
      shown to hamper the outcome of in-vitro fertilization (IVF). As UC are postulated
      to be hormone-regulated, we aimed to investigate the role of plasma oestradiol
      and progesterone concentrations on UC during ovarian stimulation for IVF. A total
      of 59 women were studied on the day of administration of human chorionic
      gonadotrophin (HCG) and embryo transfer. Plasma oestradiol and progesterone
      concentrations were measured, and 5 min ultrasound scans of the uterus were
      digitized with an image analysis system to assess UC frequency and direction.
      Cycles were sorted according to whether progesterone concentrations on the day of
      embryo transfer were < or =100 (n = 34) or >100 (n = 25) ng/ml. On the day of
      HCG, UC frequency was similar in both groups at 4.5+/-0.2 and 4.6+/-0.3 UC/min
      (mean +/- SE) respectively. On the day of embryo transfer, UC frequency remained
      steady in the low progesterone group, whereas it decreased (3.5+/-0.2 UC/min) in
      the high progesterone group (P < 0.001), and was negatively correlated with
      progesterone concentrations (r = -0.56; P < 0.001). No influence of oestradiol on
      UC was noticed. These observations confirm the utero-relaxing effects of
      progesterone in the non-pregnant uterus and support the administration of
      progesterone before embryo transfer to increase tissue concentrations and improve
      the outcome of IVF.

PMID- 10928423
TI  - The endometrium and hormonal contraceptives.
AB  - Contraceptive progestogens have a series of effects on the endometrium that
      depend on the existence of oestrogen priming and therefore on the time of
      administration, the route through which the hormone is released to the body
      (systemic or locally in utero) and the available daily dose. The effects of a
      contraceptive progestogen can be divided into two main categories: changes in the
      endometrial structure and vascularization and alterations of the menstrual
      bleeding pattern. Whereas orally administered progestogens usually cause
      endometrial decidualization and an important stromal reaction, the i.m., or
      local, intrauterine delivery is more apt to cause atrophia. Finally, all
      progestogens, when given alone at contraceptive doses (and irrespective of their
      mechanism of action), cause some disruption of menstrual bleeding patterns. This
      is maximal with injectable, long-acting progestogens, such as depot
      medroxyprogesterone acetate and norethisterone enantate.

PMID- 10928424
TI  - Morphological changes and protein secretion induced by progesterone in the
      endometrium during the luteal phase in preparation for nidation.
AB  - Progesterone induces morphological modifications and protein secretion during the
      luteal phase to permit implantation/nidation. It acts through specific receptors
      which are regulated by oestrogens. The proliferative phase is thus a prerequisite
      for progesterone activity. Changes in morphology are first located in the
      glandular component, with peak secretion occurring during the implantation
      window. The various components of the stroma are involved during the second part
      of the luteal phase, resulting in decidualization and the formation of spiral
      arteries. The subsequent fall-off in progesterone leads to menstruation. The next
      cycle begins with a regenerative process in which oestrogens induce the
      modifications typical of the proliferative phase. The luteal phase is usually
      assessed on morphological criteria but should also be accompanied by protein
      secretion profiles of glands and stroma.

PMID- 10928425
TI  - Progesterone for the luteal support of assisted reproductive technologies:
      clinical options.
AB  - The role of progesterone in luteal support in assisted reproductive technologies
      (ART) is reviewed. There is insufficient data in ART treatment without
      gonadotrophin-releasing hormone (GnRH) analogues, to prove the necessity for
      luteal phase support using progesterone. Prospective studies have shown that ART
      cycles using GnRH analogues need to be supplemented. GnRH antagonists could have
      some adverse effects on the luteal phase. So far, no prospective randomized
      comparative study has been performed to investigate the necessity for luteal
      phase support when antagonists are used in ART cycles. Clinical outcome data
      (pregnancy and abortion rates) show similar success rates for human chorionic
      gonadotrophin (HCG) or progesterone supplementation. A major disadvantage of
      using HCG is the risk of maintaining or enhancing ovarian hyperstimulation
      syndrome. Of the several routes of administration of progesterone, the vaginal
      route is preferred because of its ease of use, reduced side-effects and, most
      importantly, the first uterine pass effect.

PMID- 10928426
TI  - Vaginal progesterone in menopause: Crinone 4% in cyclical and constant combined
      regimens.
AB  - Compliance with hormone replacement therapy (HRT) is notoriously low despite
      ample documentation of clinical efficacy. The two major reasons given by women
      who discontinue HRT are uterine bleeding and side-effects. The recent development
      of a controlled and sustained vaginal progesterone gel allowed single daily
      application and made prolonged use such as for menopause possible. Here we report
      our clinical experience with two therapeutic options for HRT using natural
      progesterone administered vaginally. A first group of 69 menopausal women
      received the sustained release vaginal progesterone gel, Crinone 4% (45 mg daily)
      from days 1-10 of each calendar month with oestrogens taken continuously. A
      second group of 67 women received Crinone 4% twice weekly in conjunction with
      continuous oestrogen therapy. Endometrial thickness was evaluated before and
      after 6 months of treatment. Histological verification was obtained in all cases
      of abnormal bleeding. At 6 months, 63 out of 69 (91.9%) women receiving
      progesterone cyclically experienced predictable withdrawal bleeding. The vast
      majority, 54 (80.6%) of 67 women receiving Crinone in constant combined
      association with oestrogen therapy, remained amenorrhoeic throughout 6 months of
      therapy. All cases of abnormal bleeding were biopsied and no hyperplasia was
      seen. Our results indicate that both regimens using the sustained release vaginal
      progesterone gel controlled bleeding in HRT. Combined with the lower incidence of
      side-effects characteristic of vaginal progesterone, both vaginal progesterone
      regimens have the potential of improving HRT compliance.

PMID- 10928427
TI  - Mechanisms of uterine specificity of vaginal progesterone.
AB  - Endometrial transformations achieved by vaginal progesterone exceed those
      normally expected from the circulating concentrations obtained, this suggests
      some degree of direct vagina to uterus transport. We speculate on the different
      mechanisms involved in uterine specificity of vaginal progesterone and report
      data of a preliminary randomized study comparing progesterone concentrations in
      serum and endometrial tissue obtained from hysterectomy specimens after vaginal
      or i.m. administration. Eight post-menopausal women undergoing transabdominal
      hysterectomy were randomized to receive either vaginal progesterone gel, 90 mg,
      or i.m. progesterone formulation, 50 mg, at 08.00 and 20.00 on the day before
      surgery and at 06.00 on the day of surgery. Venous blood samples for progesterone
      measurement were drawn at 08.00 on the day before surgery and during the surgery.
      Endometrial progesterone concentrations were markedly higher in women who
      received vaginal progesterone (1.38+/-0.66 and 0.38+/-0.19 ng/mg protein, for
      vaginal and i.m. groups respectively) (P < 0.02) despite lower serum
      concentrations (4.17 < 0.56 and 32.32+/-11.06 ng/ml, for vaginal and i.m. groups
      respectively) (P < 0.001). The vaginal route induces endometrial progesterone
      concentrations that far exceed those expected from the serum progesterone
      concentrations achieved.

PMID- 10928428
TI  - Vaginal delivery of progesterone in donor oocyte therapy.
AB  - A prospective cohort study, with 345 women requiring complete progesterone
      replacement for a donor egg cycle, was used to compare Crinone 8% (90 mg
      progesterone vaginal gel) twice or once daily versus i.m. progesterone (100 mg),
      for endometrial development and pregnancy support. Endometrial histology, serum
      progesterone levels, pregnancy rates, implantation rates, and bleeding patterns
      were used as outcome measures. Mean serum progesterone concentrations on day 26
      were 19.0 + 2.3 ng/ml for twice and 11.3+/-6.5 ng/ml for once daily Crinone,
      versus 65.2+/-12.5 ng/ml in the i.m. progesterone group. Endometrial histology
      was 'in phase' for all women in the Crinone groups and most of the i.m. group.
      Though eight of 42 patients on once daily Crinone had serum progesterone levels
      under 6 ng/ml, there was no correlation with endometrial development. Only one
      patient bled on once daily Crinone before the 14th day of progesterone therapy,
      and she went on to deliver twins. Clinical pregnancy, ongoing pregnancy,
      implantation, and miscarriage rates were not statistically different among any of
      the treatment groups. Crinone 8% administered once or twice daily appears to
      produce the same endometrial development and pregnancy rates as i.m. progesterone
      in women requiring complete progesterone replacement, and without early bleeding.

PMID- 10928429
TI  - New breast cancer research: mothers and twins.

PMID- 10928430
TI  - Twin processes and twin parenting.

PMID- 10928431
TI  - Multiple perspectives.

PMID- 10928432
TI  - Thromboembolism and thromboprophylaxis in high risk surgery: facts and
      assumptions--a topic for emotions?

PMID- 10928433
TI  - Combined sciatic-femoral nerve block with 0.75% ropivacaine: effects of adding a
      systemically inactive dose of fentanyl.
AB  - To evaluate the effects of adding low-dose fentanyl to 0.75% ropivacaine during
      peripheral nerve blocks, 30 ASA physical status I-II patients undergoing hallux
      valgus repair under combined sciatic-femoral nerve block were randomly allocated
      in a double-blind fashion to receive nerve block placement with 30 mL of either
      0.75% ropivacaine alone (group: ropivacaine, n = 15) or 0.75% ropivacaine plus
      fentanyl 1 microg kg(-1) (group: ropivacaine-fentanyl, n = 15). A blinded
      observer recorded haemodynamic variables and sedation, as well as the time
      required to achieve surgical block and the first request for analgesia. Readiness
      to surgery required 10 min (5-20 min) with 0.75% ropivacaine and 10 min (3-20
      min) with the ropivacaine-fentanyl mixture. No differences in the degree of
      sedation, peripheral oxygen saturation, and haemodynamic variables were observed
      between the two groups. The degree of pain measured at first analgesic request,
      and the consumption of postoperative analgesics, was similar in the two groups,
      while the mean time from block placement to the first request for pain medication
      was 13.7 h (25-75th percentiles: 11.8-14.5 h) in the ropivacaine group and 13.9 h
      (25-75th percentiles: 10.5-14.5 h) in the ropivacaine-fentanyl group (P = not
      significant). We conclude that adding fentanyl 1 microg kg(-1) to 0.75%
      ropivacaine did not provide clinically relevant advantages in terms of onset
      time, quality and duration of combined sciatic-femoral nerve block in patients
      undergoing elective hallux valgus repair.

PMID- 10928434
TI  - Modification of the Penlon Nuffield 200 series ventilator and IPPV with a
      laryngeal mask airway.
AB  - There is a risk of regurgitation if a laryngeal mask airway is used with
      intermittent positive pressure ventilation. The lower the pressure gradient
      between airway and stomach, the less will be the likelihood of stomach
      insufflation with gas and consequent regurgitation. A flow generator ventilator,
      such as the Penlon Nuffield 200 which achieves a peak pressure at the end of
      inspiration at any given tidal volume, is likely to produce a higher peak airway
      pressure than a pressure generator. Replacing the expiratory valve by a venturi
      gives a preferable flow pattern with an inspiratory pressure plateau. At equal
      tidal volumes, the venturi modification provided a 10% lower inflation pressure
      (standard deviation 6%, P < 0.01) and a 1.8% smaller leak (P < 0.05) past the
      laryngeal mask airway. The same comparison but using identical inflation
      pressures, gave 8% larger tidal volumes (standard deviation 5.1%, P < 0.01) and a
      2% smaller leak (P < 0.01) past the laryngeal mask airway.

PMID- 10928435
TI  - Evaluation of the PhysioFlex closed-circuit anaesthesia machine.
AB  - The concentrations of nitrous oxide, sevoflurane and oxygen in the circle system
      of a closed-circuit anaesthesia machine, the PhysioFlex, were measured in seven
      patients. During anaesthesia, the settings for each gas were changed and their
      concentrations recorded. At the induction of anaesthesia, it took 80-510s (median
      190s) for the end-tidal sevoflurane concentration to reach 2.0%, and 920-2640s
      (median 1500s) for the oxygen in the breathing circuit to reach 30%. At this
      time, the nitrous oxide concentration was 60+/-3% (mean+/-SD). During
      anaesthesia, it took 90-480s (median 140s) for the end-tidal sevoflurane
      concentration setting to decrease from 3.0 to 1.0%, and 90-400s (median 110s) to
      return from 1.0 to 3.0%. When the inspired oxygen was increased from 30 to 50%,
      circuit concentrations reached equilibrium in 40-60s (median 40s), and when
      decreased from 50% back to 30%, equilibrium took 310-470s (median 450s). During
      recovery from anaesthesia, inspiratory sevoflurane concentration took 40-70s
      (median 50s) to decrease to 0.2%. The PhysioFlex provided adequate control of
      sevoflurane and oxygen concentrations, but not of increasing nitrous oxide
      concentrations.

PMID- 10928436
TI  - Inositol 1,4,5-trisphosphate synthesis in mononuclear white blood cells of
      malignant hyperthermia-susceptible and normal human beings, following in vitro
      exposure to halothane, caffeine and ryanodine.
AB  - Despite a plethora of findings associated with the pathophysiology of malignant
      hyperthermia (MH), the in vitro contracture test (IVCT) is the only reliable test
      for diagnosis of this heterogeneous syndrome in man. An increase of 1,4,5-IP3
      (inositol 1,4,5-trisphosphate), a second messenger involved in cellular calcium
      homeostasis, has been observed in muscle tissue of MH susceptible (MHS) patients.
      The aim of this study was to evaluate if the known differences of 1,4,5-IP3
      content in muscle tissue might be reproduced in mononucleated white blood cells
      (MWBCs). Subsequently, MWBCs of 23 healthy controls and 12 patients with a
      clinical suspicion for MH disposition were isolated and screened for 1,4,5-IP3
      content. An IVCT according to the protocol of the European Malignant Hyperpyrexia
      Group (EMHG) was performed on muscle specimens of 12 patients. Eight MHN and four
      MHS individuals were diagnosed. Additionally, 1,4,5-IP3 synthesis in MWBCs was
      detected following in vitro exposure to IVCT test substances halothane (2%),
      caffeine (1-30mM), and ryanodine (1-5 microM). A broad inter-individual
      variability of 1,4,5-IP3 content was observed in MWBCs of all volunteers, but no
      differences were detected between MHS and MHN individuals. These findings are in
      strong contrast to those observed in muscle tissue. In vitro exposure of isolated
      MWBCs to halothane, caffeine and ryanodine yielded no statistically significant
      differences between groups. A time- and concentration-dependent increase in
      cellular 1,4,5-IP3 content could be induced in some but not all individuals of
      both groups. Since no correlation was obtained between induction of 1,4,5-IP3
      synthesis following in vitro exposure of MWBCs to MH test substances and MH
      disposition, this study was terminated. We conclude from our data that the
      detection of 1,4,5-IP3 synthesis in MWBCs is not suitable for diagnosis of MH
      disposition. It remains questionable whether an altered 1,4,5-IP3 metabolism in
      MWBCs is involved in pathologic cascades of MH. Therefore, other cell tissues
      should be evaluated in further studies to clarify the role of the 1,4,5-IP3
      metabolism in MH.

PMID- 10928437
TI  - Evaluation of the effects of levobupivacaine on clotting and fibrinolysis using
      thromboelastography.
AB  - Amide local anaesthetics inhibit platelet function. We hypothesized that residual
      anaesthetic in the epidural space could decrease efficacy of an epidural blood
      patch in preventing postdural puncture headache. Levobupivacaine has recently
      been approved for epidural anaesthesia. Its effects on coagulation have not
      previously been studied. The aim of this study was to determine the effects of
      levobupivacaine on clotting using thromboelastography. Ten ASA Class I volunteers
      were studied. Venous blood samples were analysed using a Haemoscope 2000D TEG
      analyser. Whole blood, a 50% saline control and two levobupivacaine solutions
      (2.5 mg mL(-1) and 2.5 microg mL(-1) in blood) were compared. The former
      reproduces that produced in the epidural space by blood (20 mL for an epidural
      blood patch) and levobupivacaine 0.5% (20 mL). The latter approximates plasma
      concentrations following epidural injection of levobupivacaine 0.5% (20 mL). P <
      0.05 was considered significant. Maximum amplitude (MA), a measure of clot
      strength, is decreased by levobupivacaine 2.5 mg mL(-1). Levobupivacaine 2.5 mg
      mL(-1) decreases clot strength and may reduce efficacy of a prophylactic epidural
      blood patch.

PMID- 10928438
TI  - The influence of sufentanil and/or clonidine on the duration of analgesia after a
      caudal block for hypospadias repair surgery in children.
AB  - The aim of this study was to evaluate whether the addition of clonidine, or
      sufentanil, or both, to a bupivacaine solution for a caudal block prolonged the
      period of analgesia after operation in children. Sixty ASA class I or II boys,
      aged between 8 months and 13 years, admitted for hypospadias repair were enrolled
      into a prospective randomised study. After induction of general anaesthesia and
      endotracheal intubation the children were allocated into four groups. Group I
      received 0.5 mL kg(-1) bupivacaine 0.25% caudally, in addition group II received
      1 microg kg(-1) clonidine, group III 0.5 microg kg(-1) sufentanil and group IV
      0.5 microg kg(-1) clonidine and 0.25 microg kg(-1) sufentanil. The concentrations
      of clonidine and sufentanil in group IV were halved to reduce possible side
      effects with higher dosages. Analgesia and side-effects were assessed 2, 4, 6, 8
      and 12 h after operation. No significant differences were found among the four
      groups for the pain scores at 2, 4, 6, 8 and 12 h. All groups had a similar
      frequency of vomiting and a comparable appetite and quality of night rest during
      the first 24 h following the operation. There was no significant difference in
      the requirement for additional doses of analgesics. The addition of sufentanil,
      or clonidine, or both, to bupivacaine for caudal administration provides no
      additional clinical benefit over bupivacaine alone.

PMID- 10928439
TI  - The effects of nimodipine on vecuronium-induced neuromuscular blockade.
AB  - Nimodipine, a calcium channel blocking drug, is used in the treatment of cerebral
      arterial spasm after subarachnoid haemorrhage due to bleeding from an
      intracranial aneurysm. The purpose of this study was to evaluate the effects of
      nimodipine on neuromuscular blockade after vecuronium had been given to
      facilitate tracheal intubation and maintenance of muscle paralysis in patients
      undergoing clipping of intracranial aneurysm. Twenty patients were divided into
      two groups: a control group (n = 10) who received no calcium channel blocking
      drug, and a nimodipine group (n = 10) consisting of patients treated with
      nimodipine at clinically used doses of 0.03 mg kg(-1) h(-1) pre- and
      perioperatively. Anaesthesia was induced with atropine 10 microg kg(-1),
      dehydrobenzperidol 5 mg, fentanyl 5 microg kg(-1), thiopental 5 mg kg(-1) and
      maintained with a mixture of N2O and isoflurane (0.5-1% inspired concentration)
      in O2, and additional doses of fentanyl 2.5 microg kg(-1). Neuromuscular
      responses were monitored by acceleromyograpy. The first twitch of the train-of
      four response (T1) was considered as twitch height. After a stabilization period,
      an intubating dose of vecuronium 0.1 mg kg(-1) was administered. The onset of
      action, the time of first appearance of T1 and clinical duration of action were
      recorded. Then, maintenance doses of vecuronium 0.03 mg kg(-1) were administered
      twice more when T1 had recovered to 25% of control twitch height. The study ended
      when the recordings of the 3rd 25% T1 recovery had been obtained. There were no
      statistical differences in the onset time (120+/-44 s in the control group, 141+/
      33 s in the nimodipine group), in the first appearance time of T1 (28+/-6 min in
      the control group, 30+/-8 min in the nimodipine group), and in the times for 25%
      recovery in T1 (41+/-11, 32+/-2, 40+/-13 min in the control group, respectively,
      and 44+/-16, 36+/-15, 38+/-15 min in nimodipine group, respectively) between the
      groups studied. The time between the injection of the intubating dose of
      vecuronium and the third recovery of T1-25% of control was not significantly
      different between the control group (113+/-34 min) and the nimodipine group
      (117+/-42 min). This study indicates that nimodipine does not have any
      significant effect on the time course of action of vecuronium including the onset
      time and its clinical duration of action after the initial and the two
      maintenance doses in these patients.

PMID- 10928440
TI  - Anaesthetic implications of osteo-odonto-keratoprosthesis surgery.
AB  - Patients with bilateral corneal blindness in whom corneal transplantation has
      either been unsuccessful or inappropriate may be considered for osteo-odonto
      keratoprosthesis surgery. During a two-stage procedure the surface of the cornea
      is removed and covered with a graft of buccal mucosa. An optical cylinder,
      supported by an osteo-odonto lamina planed from a tooth is then inserted into the
      mucosa to act as a lens. The anaesthetic implications of this operation include
      care of patients from a wide age range, often with underlying medical problems
      undergoing two operations of prolonged duration. The eye can be 'open' during
      both stages of the operation and anaesthetic techniques directed towards
      prevention of rises in vitreal pressure are essential. This article outlines the
      surgical process of osteo-odonto-keratoprosthesis surgery with reference to our
      anaesthetic experiences from nine cases.

PMID- 10928441
TI  - Use of the intubating laryngeal mask for airway management and light-guided
      tracheal intubation in the lateral position.
AB  - Sudden accidental loss of the airway during surgery is potentially hazardous
      especially when the patient is lying in any position which prevents easy
      intubation of the trachea. We describe two patients lying in the lateral position
      who required urgent airway management and endotracheal intubation. In both cases
      endotracheal intubation was achieved successfully using a light-guided technique-
      with a prototype illuminated flexible catheter--through an intubating laryngeal
      mask airway.

PMID- 10928442
TI  - Rapidly developing airway obstruction resulting from achalasia of the oesophagus.
AB  - Megaoesophagus resulting from achalasia is a rare but serious cause of airway
      obstruction. The exact aetiology remains unclear. Although 29 cases have
      previously been reported, the potential need for urgent treatment has not been
      sufficiently emphasized. Some forms of treatment with drugs or decompression with
      a fine tube have been advocated but emergency tracheal intubation may become
      necessary. A 90-year-old lady had a bolus of food lodged in her oesophagus but
      with no respiratory symptoms. The bolus was removed under anaesthesia. Six weeks
      later she suffered similar symptoms after eating but developed severe airway
      obstruction over 10 min. Emergency intubation of the trachea was necessary before
      removing the food bolus under general anaesthesia. This case demonstrates the
      urgency with which these patients may need to be treated. The condition can
      rapidly worsen due to swallowing of air and saliva.

PMID- 10928443
TI  - The psychology of human error revisited.

PMID- 10928444
TI  - Continuous spinal anaesthesia or continuous epidural anaesthesia for
      postoperative pain control after hip replacement.

PMID- 10928445
TI  - Remifentanil vs. fentanyl during rigid bronchoscopy under general anaesthesia
      with controlled ventilation.

PMID- 10928446
TI  - QSAR and CoMFA: a perspective on the practical application to drug discovery.

PMID- 10928447
TI  - Applications of biomolecular NMR to drug discovery.

PMID- 10928448
TI  - Synthesis and evaluation of 4-(N,N-diarylamino)piperidines with high selectivity
      to the delta-opioid receptor: a combined 3D-QSAR and ligand docking study.
AB  - A series of 4-(N,N-diarylamino)piperidines are synthesized and evaluated for high
      affinity binding and selectivity to the delta-opioid receptor using a combination
      of 3D-QSAR and molecular docking techniques. Based on experimental ligand binding
      data to both mu- and delta- opioid receptors, CoMFA fields are generated and
      applied to identify potential ligand modifications to further optimize lead
      compounds. Molecular docking experiments to the delta-receptor are also reported
      that explain the CoMFA trends predicted as well as the differential binding and
      selectivity displayed by various compounds in the series. An analysis of the
      binding site model proposed indicates the piperidines take advantage of 3 key
      sites or binding domains within the delta-receptor. These include an aromatic
      pocket (approximately 1/3 into the receptor cavity), an aspartic acid residue
      (which serves as a docking point for the piperidinyl cationic amine) and a
      hydrophobic pocket at the extracellular boundary of the receptor cavity. Links
      are established between ligand modification and amino acid composition at these
      sites in mu and delta, providing new insight to the structural basis to binding
      and selectivity across the series and for related piperazines (i.e. SNC80 and
      BW373U86). Results are also presented that indicate delta- and mu-selectivity may
      be determined at alternate sites, suggesting opioid receptors may display
      multiple binding domains. The model is further supported by comparisons with
      opiate binding modes and site directed mutagenesis studies and is finally applied
      to suggest new strategies in ligand design.

PMID- 10928449
TI  - Conformational landscape of selective mu-opioid agonists in gas phase and in
      aqueous solution: the fentanyl series.
AB  - The conformational characteristics responsible for high affinity mu-opioid
      binding of a series of fentanyl analogs have been investigated using a
      combination of molecular mechanics and molecular dynamics techniques. In general,
      the fentanyl analogs favor a conformation that is quite different in gas phase,
      and in the presence of explicit solvent or lattice packing forces. The most
      active analogs were shown to possess an extended conformation, while fentanyl
      derivatives displaying reduced binding affinities are predicted to favor compact
      arrangements. A superposition of the proposed "bioactive conformations" across
      this ligand series identified the orientation of the N-phenethyl and the N-phenyl
      group to be a contributing factor responsible for the differential binding of the
      ohmefentanyl enantiomers, and other structural analogs. The proposed 3-point
      pharmacophore model for the fentanyls also provide insights into the structure
      activity relationship and serve as a template for further QSAR and docking
      studies.

PMID- 10928450
TI  - Substituted 3-phenylsulfonylquinazoline-2,4-dione derivatives as novel nonpeptide
      inhibitors of human heart chymase.
AB  - A series of 3-phenylsulfonylquinazoline-2,4-dione derivatives have been
      synthesized and evaluated for their ability to inhibit human heart chymase. The
      structure-activity relationship studies on these compounds gave the following
      results. The phenyl moiety of quinazoline participates in a hydrophobic
      interaction where an optimum size is required. In this moiety, 7
      chloroquinazoline is the best moiety for inhibiting chymase, chymotrypsin and
      cathepsin G. A 3-phenylsulfonyl moiety substituted with hydrophobic electron
      withdrawing groups at the 4-position potentiated the activity. Anthranil moiety
      also enhanced the activity. Pyridylmethyl and N-pyridylacetamide at the 1
      position gave an IC50 in the order of 10(-8)M. Molecular modeling studies on the
      interaction of 7-chloro-3-(4-chlorophenylsulfonyl) quinazoline-2,4(1H, 3H)-dione
      (4) with the active site of human heart chymase suggested that the phenyl moiety
      of quinazoline interacts with the hydrophobic P1 pocket, the 3-phenylsulfonyl
      moiety resides in the S1'-S2' subsites, the moiety at the 1-position locates in
      the S2-S3 subsites and the 4-carbonyl and 3-sulfonyl group interact with the
      oxyanion hole and the His57 side-chain of chymase, respectively.

PMID- 10928451
TI  - Neuronal N-type calcium channel blockers: a series of 4-piperidinylaniline
      analogs with analgesic activity.
AB  - Several novel N-type voltage sensitive calcium channel blockers showed high
      affinity in the IMR32 assay and efficacy in the anti-writhing model. Herein, we
      describe the design, synthesis, SAR studies, biological data, physicochemical
      properties and pharmacokinetics of this 4-piperidinylaniline series.

PMID- 10928452
TI  - The relation of protein binding to function: what is the significance of munc18
      and synaptotagmin binding to syntaxin 1, and where are the corresponding binding
      sites?
AB  - The Q-SNARE syntaxin 1 is a central component of the synaptic membrane fusion
      machinery. Syntaxin probably interacts with multiple proteins during synaptic
      vesicle exocytosis. In vitro, the tightest binding partners for syntaxin 1 are
      other SNAREs (synaptobrevin/VAMP and SNAP-25) and munc18-1 (also known as
      rbsec1/nsec1). Recent studies on Drosophila syntaxin led to the surprising
      finding that a syntaxin mutant which does not bind the munc18-homolog Rop
      nevertheless functionally substitutes for wild-type syntaxin in membrane fusion
      (Wu et al., Neuron 23, 593-605, 1999). This observation suggested that syntaxin 1
      binding to munc18-1 is not essential for fusion, a puzzling conclusion in view of
      the tight binding of munc18 and syntaxin homologs in all organisms. To address
      this issue, we have now reinvestigated the interaction of syntaxin with munc18
      and Rop. We find that the syntaxin sequence that was mutated in the Drosophila
      studies is not essential for munc18/Rop binding, and that the mutant is in fact
      able to bind to munc18/Rop. Thus the fact that the mutant syntaxin rescues
      release cannot be used as an argument that munc18 binding is not essential. In
      addition to munc18 and SNAREs, several other proteins have been suggested to
      interact with various domains of syntaxin 1, notably the calcium-sensor
      synaptotagmin and the vesicle protein CSP. Our results confirm that the SNARE
      motif in syntaxin binds to synaptotagmin, but this interaction does not require
      the very C-terminus of the motif. Interestingly, binding of synaptotagmin appears
      to be decreased in the closed conformation of syntaxin. In contrast, no
      interaction of CSP with syntaxin was detected even under low-stringency
      conditions. Our data suggest 1., that assays measuring protein/protein
      interactions that involve syntaxin may be more difficult to evaluate than is
      often assumed because of the sticky nature of the proteins involved, and 2., that
      it is currently not possible to draw conclusions about the importance of the
      various interactions with the available data from Drosophila or vertebrates.

PMID- 10928453
TI  - A hormone pulse induces transient changes in the subcellular distribution and
      leads to a lysosomal accumulation of the estradiol receptor alpha in target
      tissues.
AB  - An intrauterine pulse-stimulation with estradiol induced changes in the
      subcellular localization of estrogen receptor alpha in porcine endometrium, as
      detected with F(ab') fragments of various anti-receptor antibodies covalently
      linked to nanogold. The low-sterically hindered immunoreagents--recognizing
      different epitopes within the hormone binding domain--allowed for an efficient
      immunolabeling of estradiol receptor alpha, detecting it both in the cytoplasm
      and the nucleus of nonstimulated epithelium cells. In the cytoplasm, the receptor
      often seemed to be associated with actin filaments and the endoplasmatic
      reticulum. After the stimulation with estradiol, a predominantly nuclear
      localization and a labeling of nucleoli was observed. Our immunoelectron
      microscopy study demonstrates a localization of the receptor in cytoplasmic
      organelles that increased after the hormone pulse. These organelles exhibited the
      morphological properties of lysosomes and relocated to the perinuclear area. In
      analogous cytoplasmic organelles, the presence of cathepsin D was detected via
      indirect immunogold labeling, justifying their classification as lysosomes.
      Quantitative examinations revealed that not only the number of lysosomes in the
      proximity of the nucleus but also their immunostaining for estradiol receptor
      alpha increased significantly after the hormone pulse. Thus, estradiol induces
      both the rapid shift of receptor into the nucleus, a slower perinuclear
      accumulation of lysosomes and an increase of lysosomal ERalpha-immunoreactivity.
      These results suggest a role for lysosomes in the degradation of receptor
      shuttling out of the nucleus. This could serve as termination of the estradiol
      receptor alpha-dependent activation of target cells. This hypothesis is
      strengthened by the fact that the receptor content in uterine tissue declined
      drastically few hours after the hormone pulse.

PMID- 10928454
TI  - Primaquine interferes with membrane recycling from endosomes to the plasma
      membrane through a direct interaction with endosomes which does not involve
      neutralisation of endosomal pH nor osmotic swelling of endosomes.
AB  - The anti-malaria drug primaquine is a weak base which accumulates in endosomes in
      a protonated form and consequently neutralises the endosomal pH. Bafilomycin A1
      prevents endosome acidification by inhibiting the vacuolar proton pump. Although
      both agents neutralise the endosomal pH, only primaquine has a strong inhibitory
      effect on recycling of endocytosed proteins to the plasma membrane (Van Weert et
      al. (1995), J. Cell Biol. 130, 821-834). This suggests that primaquine interferes
      with a parameter, other than endosomal pH, that is essential for membrane
      recycling. In the presence of 0.3 mM primaquine, endocytosed transferrin
      receptors accumulated intracellularly, but not in the additional presence of
      bafilomycin A1. Thus, at relative low concentrations proton pump-driven
      accumulation of primaquine in endosomes was required to inhibit membrane
      recycling, suggesting that the target of primaquine is associated with endosomes.
      The inhibitory effect of 1 mM primaquine on transferrin receptor recycling was
      not reversed by the additional presence of bafilomycin A1, indicating that
      osmotic swelling of endosomes due to accumulation of protonated primaquine could
      also not explain its effect. To study endosome swelling morphologically, we
      introduce a novel technique for fluorescent labelling of endosomes involving HRP
      catalysed biotinylation. In the presence of 0.2 mM primaquine endosomal vacuoles
      with diameters up to 2 microm were observed. Endosome swelling was not observed
      when in addition to primaquine also bafilomycin A1 was present, supporting the
      notion that vacuolar proton pump activity lowers the dose response for
      primaquine. Factors that are crucial for membrane recycling and may be affected
      by primaquine are discussed.

PMID- 10928455
TI  - Secretion and differential localization of the proteolytic cleavage products
      Abeta40 and Abeta42 of the Alzheimer amyloid precursor protein in human fetal
      myogenic cells.
AB  - Abeta peptides are major components of the amyloid plaques that characterize
      Alzheimer's disease. These peptides are proteolytic cleavage products of the
      amyloid precursor protein (APP) and are generated by beta- and gamma-secretases.
      Here we show by multiparameter immunofluorescence imaging in muscle cells that
      localization of the Abeta40 and Abeta42 cleavage products reveals different
      myocyte types in a three-dimensional culture system. These myocyte types are
      heterogeneous by selective intracellular concentration of either Abeta40 or
      Abeta42 in vesicular structures, whilst only the Abeta40 peptide is secreted as
      indicated by Western blot analysis. This cellular pattern of APP proteolysis and
      Abeta peptide secretion correlates with lack of L-APP mRNA splice isoforms.
      Differential secretion and intracellular accumulation of Abeta peptides is
      characteristic for the early myocyte development and might be related to cell
      fusion.

PMID- 10928456
TI  - Modulation of the epidermal growth factor receptor by the human papillomavirus
      type 16 E5 protein in raft cultures of human keratinocytes.
AB  - It has been shown that the E5 protein of the human papillomavirus type 16
      modulates epidermal growth factor receptor downregulation in monolayer cultures
      of human keratinocytes and mouse fibroblasts. We have now analysed the effect of
      this protein on the expression, the distribution and the activation of EGF
      receptors in raft cultures derived from an E5-transfected human keratinocyte cell
      line. The epithelia generated in these cultures were stratified and exhibited
      suprabasal expression of cytokeratins 1 and 10, which are known markers of early
      epidermal differentiation. In situ hybridization with an antisense riboprobe to
      the human papilloma virus type 16 E5 protein revealed a homogeneous gene
      expression within the entire epithelium of E5-transfected but not empty vector
      transfected control cultures. Treatment of serum-starved rafts with EGF for 48
      hours led to a strong decrease of suprabasal EGF receptors in control cultures,
      but not in rafts of E5-expressing cells. Under these conditions, no activated
      receptors were observed in control cultures, but activated receptors were still
      present in E5-raft cultures. Our results indicate that human papilloma virus type
      16 E5-mediated modulation of EGF receptor expression occurs in a time- and
      structure-dependent manner in epithelial equivalents of human keratinocytes.

PMID- 10928457
TI  - Characterization, cloning and immunolocalization of a coronin homologue in
      Trichomonas vaginalis.
AB  - On adhesion to host cells the flagellate Trichomonas vaginalis switches to an
      amoeboid form rich in actin microfilaments. We have undertaken the identification
      of actin-associated proteins that regulate actin dynamics. A monoclonal antibody
      4C12 raised against a cytoskeletal fraction of T. vaginalis labeled a protein
      doublet at circa 50 kDa. These two bands were recognized by the antibody against
      Dictyostelium discoideum coronin. During cell extraction and actin
      polymerization, T. vaginalis coronin cosedimented with F-actin. By two
      dimensional gel electrophoresis, the protein doublet was separated into two sets
      of isoforms covering two Ip zones around 6 and 7. By screening a T. vaginalis
      library with 4C12, two clones Cor 1 and Cor 2 were isolated. This gene duplicity
      is a particularity among unicellular organisms examined. The complete sequence of
      the gene Cor 1 encodes a 435-residue protein with a calculated molecular mass of
      48 kDa and Ip of 5.58. The incomplete sequence Cor 2 was very similar but with a
      more basic calculated Ip than Cor 1 on the same region. T. vaginalis coronin had
      50% similarity with the coronin family, possessing the five WD-repeats and a
      leucine zipper in its C-terminal part. Double immunofluorescence labeling showed
      that coronin mainly colocalized with actin at the periphery of the adherent
      amoeboid cells. However, coronin labeling displayed patches within a reticular
      array. Immunogold electron microscopy confirmed the coronin labeling in the actin
      rich microfilamentous fringe beneath the plasma membrane, with accumulation in
      phagocytic zones and pseudopodial extensions. In T. vaginalis, one of the first
      emerging lineage of eukaryotes, coronin seems to play an important role in actin
      dynamics and may be a downstream target of a signaling mechanism for the
      cytoskeleton reorganization.

PMID- 10928458
TI  - Specific types of prosomes distribute differentially between intermediate and
      actin filaments in epithelial, fibroblastic and muscle cells.
AB  - First observed as components of non-translated mRNP complexes, prosomes harbour
      RNase and several proteinase activities; they are also the central constituent of
      the "Multicatalytic Proteinase (MCP) complexes" or "26S-proteasomes". In two
      recent publications (Arcangeletti et al., 1997b; De Conto et al., 1997) we have
      shown, by applying a new fixation technique, that these particles distribute
      differentially between the cytoskeletal networks of intermediate filament (IF)
      and actin types; previously they had been observed exclusively on the
      intermediate filaments. Here we further investigate the distribution of prosomes
      of several types, distinct by their subunit composition, between the IF of
      vimentin type and the actin network, as well as in the 3D space of the cell. It
      is shown that subtypes of prosomes occupy specific networks of the cytoskeleton,
      and that this pattern is specific for a given cell type. Confocal microscopy
      shows that prosome cytodistribution is not homogeneous in the 3D space: in the
      perinuclear area they colocalize most strongly with the IF, and more peripherally
      with the microfilament/stress fiber system; connections may exist between the two
      networks. Furthermore, new data indicate that the prosome-actin interaction may
      participate in the molecular structure of the stress fibers.

PMID- 10928459
TI  - Localization of gamma-tubulin in interphase and mitotic cells of a unicellular
      eukaryote, Giardia intestinalis.
AB  - Giardia intestinalis, a bi-nucleated amitochondrial flagellate, possesses a
      complex cytoskeleton based on several microtubular systems (flagella, adhesive
      disk, median body, funis, mitotic spindles). MTOCs of the individual systems have
      not been fully defined. By using monoclonal antibodies against a conserved
      synthetic peptide from the C-terminus of human gamma-tubulin we investigated
      occurrence and distribution of gamma-tubulin in interphase and mitotic Giardia
      cells. On the immunoblots of Giardia cytoskeletal extracts the antibodies bound
      to a single polypeptide of approximately 50 kDa. Immunostaining of the interphase
      cell demonstrated gamma-tubulin as four bright spots at the basis of four out of
      eight flagella. Gamma-tubulin label was associated with perikinetosomal areas of
      the ventral and posterolateral pairs of flagella which are formed de novo during
      cell division. Basal body regions of the anterolateral and caudal pairs of
      flagella which persist during the division and are integrated into the flagellar
      systems of the daughter cells did not show gamma-tubulin staining. At early
      mitosis, gamma-tubulin spots disappeared reappearing again at late mitosis in
      accord with reorientation of parent flagella and reorganization of flagellar
      apparatus during cell division. The antibody-detectable gamma-tubulin epitope was
      absent at the poles of both mitotic spindles. Albendazole-treated Giardia, in
      which spindle assembly was completely inhibited, showed the same gamma-tubulin
      staining pattern thus confirming that the fluorescent label is exclusively
      located in the basal body regions. Our results point to a role of gamma-tubulin
      in nucleation of microtubules of newly formed flagella and indicate unusual
      mitotic spindle assembly. Moreover, the demonstration of gamma-tubulin in Giardia
      shows ubiquity of this protein through the evolutionary history of eukaryotes.

PMID- 10928460
TI  - Renewed interest in haemostasis changes induced by oral contraceptives (OCs)

PMID- 10928461
TI  - Effects on coagulation of levonorgestrel- and desogestrel-containing low dose
      oral contraceptives: a cross-over study.
AB  - Combined oral contraceptives (OC) are known to increase the risk of venous
      thromboembolism. The aim of this randomized, cycle-controlled, cross-over study
      in 28 healthy volunteers was to assess potential differences between the effects
      of an OC containing 150 microg levonorgestrel (as representative of the so-called
      second generation OC) and an OC containing 150 microg desogestrel (as
      representative of the third generation OC) in combination with 30 microg
      ethinylestradiol on several coagulation factors and markers of thrombin
      formation. All participants used each OC for two cycles, and were switched to the
      other OC after a washout period of two menstrual cycles. The plasma
      concentrations of factors II, VII, X, and fibrinogen significantly increased
      during use of both the levonorgestrel- and desogestrel-containing OC's. The
      plasma concentrations of factor VIII increased, and of factor V decreased,
      changes which only reached statistical significance during the use of the
      desogestrel-containing OC. During exposure to the desogestrel-containing OC, as
      compared with the levonorgestrel-containing OC, both factor VII and factor II
      showed a greater increase (FVII: 32% and 12% respectively; p <0.0001; FII: 16%
      and 12% respectively; p = 0.048), whereas factor V showed a greater decrease (
      11% and -3% respectively; p = 0.010). Only one of the markers for ongoing
      coagulation (prothrombin fragment 1+2) showed a significant increase during OC
      use, whereas concentrations of thrombin-antithrombin complexes and soluble fibrin
      remained unchanged. For these markers, there was no difference between the tested
      OC's. We conclude that there are differences between the effects of
      levonorgestrel and desogestrel-containing OC's on some coagulation factors.
      Whether these changes provide a biological explanation for the reported
      differences in venous thromboembolic risk is as yet unclear. The real challenge
      now becomes to define a pattern of changes in the various systems which, if
      affected simultaneously, may tip the hemostatic balance towards a prethrombotic
      state and may lead to overt clinical venous thromboembolism.

PMID- 10928464
TI  - Nomograms for the administration of unfractionated heparin in the initial
      treatment of acute thromboembolism--an overview.
AB  - Despite the availability of low-molecular-weight heparins, unfractionated heparin
      (UFH) still remains the drug of choice for the initial treatment of acute venous
      thromboembolism in many countries. When appropriately employed, UFH treatment
      results in a degree of efficacy and safety that is fully comparable with that
      obtained with the use of heparin derivatives. The use of nomograms for the
      intravenous or subcutaneous administration of UFH assures that virtually all
      patients will promptly achieve adequate levels of anticoagulation, thus
      decreasing the likelihood of recurrent venous thromboembolism without extra
      bleeding-risk. In this article we reviewed clinical studies on the implementation
      and validation of UFH dosing nomograms, and attempted a quantitative analysis of
      their performance. According to the results of our analysis, a statistically
      significantly higher proportion of patients treated on the basis of a nomogram
      reached a therapeutic anticoagulant level within 24 h of treatment, as compared
      to patients treated following the standard practice (odds ratio, 3.6; 95% CI, 2.6
      to 4.9). The rate of recurrent thromboembolic events was significantly lower for
      patients treated according to a nomogram (odds ratio, 0.3; 95% CI, 0.1 to 0.8),
      while no significant differences in terms of either major or minor bleedings were
      detected between nomogram patients and controls.

PMID- 10928462
TI  - Increased fibrinolytic activity during use of oral contraceptives is counteracted
      by an enhanced factor XI-independent down regulation of fibrinolysis: a
      randomized cross-over study of two low-dose oral contraceptives.
AB  - The effect of oral contraceptives (OC) on fibrinolytic parameters was
      investigated in a cycle-controlled cross-over study in which 28 non-OC using
      women were randomly prescribed either a representative of the so-called second
      (30 microg ethinylestradiol, 150 microg levonorgestrel) or third generation OC
      (30 microg ethinylestradiol, 150 microg desogestrel) and who switched OC after a
      two month wash out period. During the use of OC, the levels of tissue-type
      plasminogen activator (tPA) activity, plasminogen, plasmin-alpha2-antiplasmin
      complexes and D-dimer significantly increased (by 30 to 80%), while the levels of
      plasminogen activator inhibitor- (PAI-1) antigen, PAI-1 activity and tPA antigen
      significantly decreased (25 to 50%), suggesting an increase in endogenous
      fibrinolytic activity. These OC-induced changes were not different between the
      two contraceptive pills. TAFI (thrombin-activatable fibrinolysis inhibitor)
      levels increased on levonorgestrel, and even further increased on desogestrel. A
      clot lysis assay that probes both fibrinolytic activity and the efficacy of the
      coagulation system to generate thrombin necessary to down regulate fibrinolysis
      via TAFI showed no change of the clot lysis time during OC use. This finding
      suggests that the OC-induced increase in endogenous fibrinolytic activity is
      counteracted by an increased capacity of the coagulation system to down regulate
      fibrinolysis via TAFI. Indeed we observed that during OC use there was a
      significant increase of F1+2 generation during clot formation. When these assays
      were performed in the presence of an antibody against factor XI, we observed that
      the clot lysis time was significantly increased during OC use and that the
      increase in F1+2 generation during OC therapy was due to a factor XI-independent
      process, which was significantly higher on desogestrel than on levonorgestrel.
      These data indicate that the OC-induced inhibition of endogenous fibrinolysis
      takes place in a factor XI-independent way and is more pronounced on desogestrel
      than on levonorgestrel-containing OC.

PMID- 10928465
TI  - Homocysteine as a risk factor for restenosis after coronary angioplasty.
AB  - We examined the relationship between plasma homocysteine levels and restenosis
      after PTCA (Percutaneous transluminal coronary angioplasty) to investigate
      whether plasma homocysteine levels can be a predictor of restenosis after PTCA.
      One hundred and twelve male patients who have undergone a successful elective
      PTCA were consecutively enrolled and plasma homocysteine levels were measured at
      the time of follow-up angiography. Plasma homocysteine levels in patients with
      restenosis were significantly higher than those in patients without restenosis
      (15.0 +/- 3.9 vs. 13 +/- 2.9 micromol/L; P = 0.011). The difference was augmented
      when diabetic patients were selectively studied. The comparison between
      restenosis group and non-restenosis group indicated the threshold effect of
      hyperhomocysteinemia. These results suggest that plasma homocysteine is a
      potential risk factor of restenosis after PTCA, and therapeutic strategy targeted
      against hyperhomocysteinemia may be beneficial for preventing restenosis.

PMID- 10928463
TI  - A randomized cross-over study on the effects of levonorgestrel- and desogestrel
      containing oral contraceptives on the anticoagulant pathways.
AB  - The use of oral contraceptives (OC) causes disturbances of the procoagulant,
      anticoagulant and fibrinolytic pathways of blood coagulation which may contribute
      to the increased risk of venous thrombosis associated with OC therapy. Here we
      report the results of a cycle-controlled randomized cross-over study, in which we
      determined the effects of so-called second and third generation OC's on a number
      of anticoagulant parameters. In this study, 28 non-OC using women were randomly
      prescribed either a second generation (150 microg levonorgestrel/30 microg
      ethinylestradiol) or a third generation OC (150 microg desogestrel/30 microg
      ethinylestradiol) and who switched to the other OC after a two month wash out
      period. The anticoagulant parameters determined were: antithrombin (AT), alpha2
      macroglobulin (alpha2-M), alpha1-antitrypsin, protein C inhibitor (PCI), protein
      C, total and free protein S and activated protein C sensitivity ratios (APC-sr)
      measured with two functional APC resistance tests which quantify the effect of
      APC on either the activated partial thromboplastin time (aPTT) or on the
      endogenous thrombin potential (ETP). During the use of desogestrel-containing OC
      the plasma levels of alpha2-M, alpha1-antitrypsin, PCI and protein C
      significantly increased, whereas AT and protein S significantly decreased.
      Similar trends were observed with levonorgestrel-containing OC, although on this
      kind of OC the changes in AT, PCI and protein S (which was even slightly
      increased) did not reach significance. Compared with levonorgestrel, desogestrel
      containing OC caused a significant decrease of total (p <0.005) as well as free
      protein S (p <0.0001) and more pronounced APC resistance in both the aPTT (p =
      0.02) and ETP-based (p <0.0001) APC resistance tests. These observations indicate
      that the activity of the anticoagulant pathways in plasma from users of
      desogestrel-containing OC is more extensively impaired than in plasma from users
      of levonorgestrel-containing OC.

PMID- 10928466
TI  - Ontogeny of beta 2 glycoprotein I and annexin V in villous placenta of normal and
      antiphospholipid syndrome pregnancies.
AB  - beta2-glycoprotein I (beta2GPI) and annexin V (AV) have been implicated in the
      pathophysiology of the antiphospholipid syndrome (APS). We investigated their
      placental expression in normal villous tissues throughout gestation; first
      trimester n = 10, early second trimester; n = 4, preterm; n = 5) and term; n = 7
      and in APS (2 first trimester, 1 preterm and 8 term deliveries). beta2GPI and AV
      were both expressed by the placenta from as early as seven weeks gestation and
      were colocalised to the syncytiotrophoblast. beta2GPI staining was also observed
      in stromal cells, being present in phagocytic Hofbauer cells and surrounding
      newly formed fetal vessels in a perivascular pattern, from seven to seventeen
      weeks gestation. An abnormal morphological distribution of AV was noted in one
      first trimester APS placenta, and for beta2GPI in a further first trimester
      placenta. When placental proteins were extracted from villous tissue, the
      concentration of AV/mg protein in term APS placentas (median, interquartile
      range) (aPS; 8.16, 7.879.72 microg/mg) was significantly higher (p <0.005) than
      normal term levels (normal; 2.47, 2.28-2.54 microg/mg). beta2GPI increased with
      advancing gestation (first trimester; 0.93, 0.64-1.26 microg/mg, term; 3.67, 2.58
      4.48 microg/mg) in normal pregnancy. Term APS placentas had a reduced beta2GPI
      content (2.31, 1.87-2.49 microg/mg), p <0.05. The placental role of these
      proteins remains to be identified.

PMID- 10928467
TI  - The influence of (R)- and (S)-warfarin, vitamin K and vitamin K epoxide upon
      warfarin anticoagulation.
AB  - The contribution of (R)- and (S)-warfarin enantiomers, vitamin K and vitamin K
      epoxide and patient factors to inter-individual variability in daily warfarin
      requirements were examined in a group of 73 patients. Simple correlation analysis
      showed a significant positive relationship between INR values and plasma (S)
      warfarin concentrations (r = 0.25; p = 0.038). Multivariate analysis for
      relationships with INR demonstrated a highly significant positive relationship
      between INR and (S)-warfarin (p = 0.004) and plasma vitamin K epoxide
      concentrations (p = 0.028), and a significant negative relationship between INR
      and plasma vitamin K concentrations (p = 0.034). Twenty five percent of variation
      in INR could be explained by these variables (adjusted R2 = 0.25). Correlation
      analysis of data showed that warfarin dosage was significantly and negatively
      correlated with patient age (r = -0.42; p <0.0001). Patient age accounted for 25%
      of variation in warfarin dosage requirements (R2 = 0.25). The combined effects of
      age and vitamin K appear to account for much of the inter-individual variability
      in warfarin dosage requirements.

PMID- 10928468
TI  - Characterization of a monoclonal antibody, D73H, that maps to a highly conserved
      region on fibrinogen Bbeta chain.
AB  - The primary structure of fibrinogen is highly conserved across species, yet often
      times monoclonal antibodies produced against the fibrinogen of one species will
      not crossreact with the fibrinogen of another. Herein, we describe the production
      and characterization of murine MAb, D73H, raised against human fibrinogen. D73H
      crossreacts with a highly conserved epitope on the Bbeta chain of fibrinogen from
      human, rat, bovine, guinea pig, and mouse. Western blotting revealed that D73H
      reacted with the Bbeta chain of plasmin fragment D, localizing its epitope to
      Bbeta134-461. A 7 kDa band was identified by D73H in Western blots of reduced
      fibrinogen CNBr-fragments. N-terminal sequencing mapped this fragment to Bbeta243
      253, further localizing the epitope to Bbeta243-305. In silico analysis indicated
      that Bbeta243-305 is predominantly hydrophilic, and surface probability
      prediction indicated three potential antigenic determinants corresponding to
      Bbeta252-258, Bbeta262-269, and Bbeta279-286. Further in silico analysis of the
      crystal structure of fibrinogen fragment D-D indicated that Bbeta262-269
      (FGRKWDPY) is predominantly alpha-helical and located on the surface of the
      molecule adjacent to a bend imposed in the beta chain at residue 260, which is
      near the junction between the rigid coiled-coil domain and the globular C
      terminus. A synthetic peptide corresponding to Bbeta261-272 competitively
      inhibited the binding of D73H to the Bbeta chain of denatured intact fibrinogen
      and reduced and denatured Bbeta chain in Western blots, experimentally proving
      the validity of these predictive algorithms. Together these data indicate that,
      although plasmin resistant, Bbeta chain residues Bbeta261-272 comprising the D73H
      epitope are highly conserved across species, surface exposed, and immunogenic.

PMID- 10928469
TI  - A case of congenital afibrinogenemia: fibrinogen Hakata, a novel nonsense
      mutation of the fibrinogen gamma-chain gene.
AB  - Congenital afibrinogenemia due to a novel homozygous nonsense mutation of the
      fibrinogen gamma-chain gene, fibrinogen Hakata, was found in an 18-year-old
      Japanese girl who had received supplemental fibrinogen therapy since she was 4
      months old. The plasma fibrinogen concentrations of the proband were measured as
      less than 10 mg/dl by a functional method and less than 17 mg/dl by an
      immunological method. Fibrinogen concentrations of her family were in the range
      of 94-164 mg/dl. The proband and her family had no other clinical symptoms.
      Genomic DNA of the proband and her family was isolated from leukocytes, and all
      exons of fibrinogen subunits and their intron/exon boundaries were analyzed. A
      genetic mutation, a guanine-to-thymine (G-to-T) transversion at the nucleotide
      position of 5860, was identified on exon 7 of the gamma-chain gene. This mutation
      changed the codon for the 231st residue of the gamma-chain from GAG (Glu) to TAG
      (stop). No other mutation was observed. Aalpha, Bbeta and gamma chains were
      observed in plasma of the heterozygous family members. However, only a trace
      amount of Aalpha chain and no gamma chain was detected in the plasma of the
      proband.

PMID- 10928470
TI  - Effect of urinary protein C inhibitor on lipopolysaccharide-induced disseminated
      intravascular coagulation in rats.
AB  - The effect of urinary protein C inhibitor (uPCI) on disseminated intravascular
      coagulation (DIC) was investigated using an experimental DIC in rats. uPCI (0.5
      and 1.0 mg/kg) was continuously administrated into the left femoral vein of the
      rats with lipopolysaccharide (50 mg/kg)-induced DIC. In all doses, uPCI
      significantly prevented the drastic changes in the parameters such as fibrinogen
      concentration, activated partial thromboplastin time (APTT), prothrombin time
      (PT), fibrin/fibrinogen degradation products (FDP) level, aspartate amino
      transferase (AST) level and alanine aminotransferase (ALT) level. Furthermore,
      uPCI significantly inhibited the increase in the levels of plasma kallikrein and
      thrombin which act not only as the procoagulant proteases but also as the
      chemotactic factors to neutrophils and monocytes. These results show that uPCI
      may prevent hypercoagulation, the induction of secondary fibrinolysis and organ
      failure in the DIC model. Therefore, uPCI may be a useful agent for the clinical
      treatment of DIC.

PMID- 10928471
TI  - Fluvastatin inhibits basal and stimulated plasminogen activator inhibitor 1, but
      induces tissue type plasminogen activator in cultured human endothelial cells.
AB  - The effects of fluvastatin, a synthetic hydroxymethylglutaryl coenzyme A (HMG
      CoA) inhibitor, on the biosynthesis of tissue plasminogen activator (t-PA) and of
      its major physiological inhibitor (plasminogen activator inhibitor type 1, PAI-1)
      were investigated in cultured human umbilical vein endothelial cells (HUVEC).
      Fluvastatin (0.1 to 2.5 microM), concentration-dependently reduced the release of
      PAI-1 antigen by unstimulated HUVEC, subsequent to a reduction in PAI-1 steady
      state mRNA levels and de novo protein synthesis. In contrast, it increased t-PA
      secretion. The drug also reduced PAI-1 antigen secreted in response to 10
      microg/ml bacterial lipopolysaccharide (LPS), 100 U/ml tumour necrosis factor
      alpha (TNFalpha) or 0.1 microM phorbol myristate acetate (PMA). Mevalonate (100
      microM), a precursor of isoprenoids, added to cells simultaneously with
      fluvastatin, suppressed the effect of the drug on PAI-1 both in unstimulated and
      stimulated cells as well as on t-PA antigen. Among intermediates of the
      isoprenoid pathway, all-transgeranylgeraniol (5 microM) but not farnesol (10
      microM) prevented the effect of 2.5 microM fluvastatin on PAI-1 antigen, which
      suggests that the former intermediate of the isoprenoid synthesis is responsible
      for the observed effects.

PMID- 10928472
TI  - Prevention of renal fibrin deposition in endotoxin-induced DIC through inhibition
      of PAI-1.
AB  - Plasminogen activator inhibitor-1 (PAI-1) increases in endotoxemia thus possibly
      cooperating in altering the hemostatic balance in a prothrombotic direction. The
      effect of the inhibition of PAI-1 with the monoclonal antibody MA-33B8 was
      studied systemically and in kidneys in a lapine model of endotoxin-induced
      disseminated intravascular coagulation (DIC). The increase in plasmatic PAI
      activity in the control group (n = 9) was inhibited in the MA-33B8 treated
      rabbits (n = 5). Control rabbits showed renal fibrin deposits, whereas only one
      of the MA-33B8 rabbits did so. These results were confirmed immunohistochemically
      in kidneys as PAI-1 immunostaining was seen inside the glomeruli and larger
      vessels in the control group, whereas MA-33B8 rabbits showed a remarkable
      decrease, demonstrating that MA-33B8 successfully inhibited PAI-1 in the kidneys
      as well. Therefore evidence for the important role of PAI-1 in fibrin generation
      in endotoxin-induced DIC is presented, suggesting that strategies aiming at its
      reduction can be useful in this pathology.

PMID- 10928473
TI  - Plasminogen binding properties of macrophage inflammatory protein (MIP)-2alpha.
AB  - The chemokine macrophage inflammatory protein (MIP)-2alpha was identified as a
      plasminogen binding protein by phage display analysis. MIP-2alpha and a truncated
      form lacking 5 lysine residues in the COOH-terminal region (mut-MIP-2alpha) were
      expressed in E. coli and purified to apparent homogeneity. Purified MIP-2alpha
      but not mut-MIP-2alpha bound specifically to plasminogen, with K(A) of 3.7 X
      10(5) M(-1) for the interaction of plasminogen with surface-bound MIP-2alpha.
      Binding and competition experiments indicated that the interaction involves the
      region comprising the first 3 kringles of plasminogen and the COOH-terminal
      lysine-rich domain of MIP-2alpha. Activation of plasminogen bound to surface
      associated MIP-2alpha by two-chain urokinase-type plasminogen activator (tcu-PA)
      was about 2.5-fold more efficient than in solution (catalytic efficiency
      k(cat)K(M) of 0.1 microM(-1)s(-1), as compared to 0.04 microM(-1)s(-1). In
      contrast, binding of plasminogen to MIP-2alpha in solution was very weak, as
      evidenced by the absence of competition of MIP-2alpha with lysine-Sepharose or
      with human THP-1 cells for binding of plasminogen. In agreement with this
      finding, addition of excess MIP-2alpha did not affect the main functional
      properties of plasmin(ogen) in solution, as indicated by unaltered activation
      rates of plasminogen by tcu-PA or tissue-type plasminogen activator (t-PA), t-PA
      mediated fibrinolysis, and inhibition rate of plasmin by alpha2-antiplasmin.
      Thus, association of MIP-2alpha with surfaces exposes its COOH-terminal
      plasminogen-binding site, and may result in enhanced local plasmin generation.

PMID- 10928474
TI  - Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism, coronary
      thrombosis, and myocardial infarction in middle-aged Finnish men who died
      suddenly.
AB  - High plasminogen activator inhibitor-1 (PAI-1) plasma levels increase future risk
      of myocardial infarction (MI). The 4G allele of the 4G/5G polymorphism of the PAI
      1 gene has been associated with increased plasma levels of PAI-1. The association
      of the PAI-1 polymorphism with coronary narrowings, coronary thrombosis and
      myocardial infarction (MI) was studied in a prospective autopsy series of 300
      middle-aged Caucasian Finnish men (33 to 69 yrs) suffering sudden out-of-hospital
      death (Helsinki Sudden Death Study). The 4G allele was found in 76.8% of men with
      sudden cardiac death (SCD) compared to 67.5% in men who died accidentally and
      63.2% in men who died of other diseases (p = 0.08 and p = 0.055, respectively).
      Men possessing the 4G allele had more often acute MI (OR 3.5; p <0.05) and
      coronary thrombosis (OR 5.5. p = 0.01) compared to 5G homozygotes. 5G
      homozygotes, comprising one third of the men in our study, seem to be at a
      decreased risk of thrombosis, whereas carriers of the common 4G allele have an
      increased risk of thrombosis, AMI and possibly SCD compared to 5G homozygotes.

PMID- 10928475
TI  - Fibrinogen, fibrin and crosslinking in aging arterial thrombi.
AB  - The assumption that fibrin and crosslinked fibrin impart irreversibility to
      arterial thrombi is explored with procedure developed for measuring changes in
      platelet function, morphology and fibrinogen metabolism in aging occlusive
      thrombi, in which the condition of stasis is imposed uniformly. Arterial thrombi
      containing autologous (111)In labeled platelets were generated in vivo by
      bilateral mechanical injury of porcine carotid arteries. Vessels containing the
      platelet-rich thrombi were harvested and incubated intact (37 degrees C) for
      intervals ranging from 30 min to 12 h. The isolated vessels were then bisected
      and agitated in culture medium containing tick anticoagulant and hirudin for 60
      min. Disaggregated platelets were evaluated for yield (from (111)In
      radioactivity) viability (dense body ATP secretion) and morphology (electron
      microscopy). Western analysis of fibrin(ogen) in thrombus extracts was performed
      using anti-fibrinogen Bbeta- and gamma-chain monoclonal antibodies for thrombi at
      each time point. A stable recovery of nearly 50% of platelets was observed during
      12 h of thrombus aging. As thrombi aged, viability of disaggregated platelets
      gradually decreased with platelet necrosis the predominant feature beyond 6 h. By
      western analysis of thrombus extracts, nearly 50% of fibrinogen was cleaved to
      fibrin and extensively crosslinked within 30 min of injury with no evidence of
      fibrinolysis. With the exception of a declining proportion of gamma-monomer,
      these features remain relatively constant during 12 h of thrombus maturation. It
      is concluded that neither fibrin nor crosslinked fibrin are dominant factors
      imparting cohesion within platelet thrombi. Furthermore, under conditions of
      complete arterial occlusion imposed by this experimental design, there is no
      evidence of endogenous fibrinolysis.

PMID- 10928476
TI  - Comparison of the O'Brien filter test and the PFA-100 platelet analyzer in the
      laboratory diagnosis of von Willebrand's disease.
AB  - Von Willebrand's disease (vWD) is the most common congenital haemorrhagic
      diathesis, characterized by the quantitative or qualitative disorder of von
      Willebrand factor (vWF). A number of methods have been used for the diagnosis of
      the disease, and the bleeding time determination is widely accepted as a
      screening test in spite of its low sensitivity. Our aim was to evaluate and
      compare the performance of two high shear systems (the O'Brien filter test and
      the PFA-100 device) in the screening and diagnosis of vWD. Thirty patients (n=13
      type 1 with mild symptoms, n = 9 type 1 with severe symptoms, n = 2 type 2A, n =
      3 type 2B and n = 3 type 3 vWD) and twenty controls were investigated. In mild
      vWD the platelet retention in the second phase of the filter test with citrated
      blood showed the highest sensitivity (91.6%). The sensitivity of the PFA-100
      method with collagen-epinephrine cartridges in this group was 76.9%, while the
      bleeding time was prolonged only in 15.4% of the cases. In severe type 1, in type
      2A and type 3 all functional tests reflected the bleeding tendency of the
      patients. In type 2B disease the bleeding time was prolonged only when the
      patient was thrombocytopenic, but both high shear systems revealed the disease
      independently of the presence of thrombocytopenia. The overall sensitivity of the
      bleeding time determination was 50% compared to the 80-90% sensitivity of the
      O'Brien filter test and the PFA-100 system. The sensitivity values of the filter
      test and the PFA-100 device with collagen-epinephrine cartridges were in the same
      range, but the collagen-ADP cartridges showed a lower (65.5%) sensitivity, though
      the results were specific and had high positive predictive value. We conclude
      that both high shear systems are suitable for the screening of vWD, and that they
      are superior to the traditional bleeding time determination in case of mild
      disease or type 2B vWD.

PMID- 10928477
TI  - Assessment of primary hemostasis by PFA-100 analysis in a tertiary care center.
AB  - We evaluated the utility of the PFA-100 platelet function analyzer in identifying
      disorders in platelet function and/or von Willebrand factor (vWF) in patients
      with various systemic disorders being followed at a tertiary care center. Closure
      times were determined with collagen/ ADP (CADP) and collagen/epinephrine (CEPI)
      cartridges for 305 patients, and abnormal results were further evaluated with
      platelet aggregometry and vWF analysis. Prolonged CADP and/or CEPI closure times
      were identified in 114 patients (37.3%), but most were isolated prolonged CEPI
      closure times predominantly due to aspirin therapy (79 patients). Prolonged CADP
      closure times were most frequently due to qualitative platelet defects and/or
      decreased vWF levels. Prolonged CADP closure times were encountered most
      frequently in patients with sickle cell disease and were associated with a
      decreased hematocrit. This study demonstrated that the PFA-100 analyzer can
      accurately assess vWF-dependent platelet function and detect other platelet
      defects under high shear stress in complex patient populations.

PMID- 10928478
TI  - Monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and
      Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.
AB  - The antithrombotic effect of antiplatelet agents is principally due to their anti
      aggregatory action, but these agents may also interfere with coagulation. We have
      investigated the effect of monoclonal antibodies (MAb) to platelet membrane
      glycoproteins (GP) IIb/IIIa and Ibalpha on thrombin generation. Antibodies to
      platelet membrane glycoprotein IIb/IIIa (RFGP56 and c7E3) were shown to inhibit
      platelet-mediated thrombin generation stimulated by both intrinsic and extrinsic
      methods. An antibody to GP Ibalpha (RFGP37) also inhibited thrombin generation in
      these systems. FITC-annexin V was used to determine the effect of these
      antibodies on the exposure of procoagulant phospholipids on the platelet
      membrane, and it was found that the anti-IIb/IIIa antibodies reduced this,
      whereas the anti-Ibalpha antibody caused an increase. We conclude that our
      monoclonal antibodies against platelet membrane glycoproteins IIb/IIIa and
      Ibalpha inhibit platelet dependent thrombin generation by different mechanisms.

PMID- 10928479
TI  - Role of the leucine-rich domain of platelet GPIbalpha in correct post
      translational processing--the Nancy I Bernard-Soulier mutation expressed on CHO
      cells.
AB  - The mechanisms governing the biosynthesis and surface expression of platelet
      adhesive receptors on parent megakaryocytes are as yet poorly understood. In
      particular, the assembly and processing of the multisubunit glycoprotein (GP) Ib
      IX-V complex, a receptor for von Willebrand factor (vWf) is not fully understood.
      In the present work, these questions were addressed by reproducing a natural
      mutation of GPIbalpha found in a variant case of Bernard-Soulier syndrome (Nancy
      I), due to the deletion of leucine 179 in the seventh leucine-rich repeat of the
      polypeptide. Wild type and mutated GPIbalpha were transfected into CHO cells
      expressing GPlbbeta and GPIX. Flow cytometry showed surface expression of the
      three subunits of both GPIb-IX complexes, but GPlbalphadeltaLeu was present at
      lower levels (20-40%) and was recognized only by a sub class of monoclonal
      antibodies which epitopes were not modified by the mutation. These properties
      reproduce the defect found in the patient's platelets, demonstrating the
      causative nature of the mutation and validate the use of the CHO cells model.
      Biochemical studies were performed in an attempt to elucidate the mechanism of
      the conformational change of GPIbalphadeltaLeu. They unexpectedly revealed a
      major glycosylation deficiency of the mutated GPIbalpha leading to a 40% decrease
      in molecular weight. The other two subunits of the complex were however normal
      and present at the plasma membrane. The deletion led to complete functional
      deficiency with lack of vWf binding of CHOalphadeltaLeu transfected cells in the
      presence of botrocetin and defective adhesion to a vWf coated surface under
      static conditions. Finally, in contrast to normal CHOalphabetaIX cells, which
      displayed rolling and deceleration when perfused over a vWf surface,
      CHOalphadeltaLeubetaIX cells were unable to roll over or attach to a vWf
      substratum. These results show that the integrity of the leucine-rich region of
      GPIbalpha is essential for normal processing and function of the GPIb-IX complex.
      In addition, these results obtained in a cellular system supported the suspected
      role of the macroglycopeptide region of GPIbalpha in maintaining a suitable
      conformation of this multisubunit receptor to perform its adhesive function.

PMID- 10928480
TI  - Homozygous Pro74-->Arg mutation in the platelet glycoprotein Ibbeta gene
      associated with Bernard-Soulier syndrome.
AB  - Bernard-Soulier syndrome (BSS) is an autosomal recessive bleeding disorder due to
      quantitative or qualitative abnormalities in the glycoprotein (GP) Ib/IX/V
      complex, the platelet receptor for von Willebrand factor. This complex is
      composed of four subunits, GPIbalpha, GPIbbeta, GPIX and GPV. We describe here
      the genetic basis of the disorder in a patient with BSS. Flow cytometric analysis
      of the patient's platelets showed greatly reduced GPIbalpha and GPIX surface
      expression. Immunoblot analysis disclosed absence of GPIbalpha, GPIbbeta and GPIX
      in the platelets. DNA sequencing analysis revealed a novel missense mutation in
      the GPIbbeta gene that converts Pro (CCG) to Arg (CGG) at residue 74.
      Homozygosity of the mutation was confirmed by allele-specific restriction
      analysis, chromosome 22 microsatellite analysis and quantitative Southern
      blotting. The mutant GPIbbeta was normally transcribed. Transient transfection
      studies confirmed that mutant GPIbbeta impairs surface expression of GPIb/IX,
      showing that the mutation is responsible for a BSS phenotype observed in the
      patient.

PMID- 10928481
TI  - Effect of strenuous arm exercise on oxidized-LDL-potentiated platelet activation
      in individuals with spinal cord injury.
AB  - This study investigates how strenuous arm exercise affects oxidized-low density
      lipoprotein (O(X)-LDL) mediated-platelet activation in patients with SCI. Ten
      patients with SCI and ten age- and sex-matched healthy subjects exercised
      strenuously using an arm crank ergometer. The following measurements were taken
      both when the subjects were at rest, and immediately after exercise: plasma lipid
      profile, O(X)-LDL mediated platelet aggregability and [Ca(2+)]i, urinary 11
      dehydro-thromboxane B2 (11-dehydro-TXB2) and 8-iso-prostaglandin F(2alpha), (8
      iso-PG F(2alpha)) contents, and plasma NO metabolite (nitrite plus nitrate)
      level. Based on these measurements, the major findings of this study can be
      summarized as follows: 1) the SCI group had higher urinary 8-iso-PGF(2alpha) and
      11-dehydro-TXB2 contents, but a lower plasma nitrite plus nitrate level than the
      control group; 2) at rest, the SCI group had a higher platelet aggregability and
      [Ca(2+)]i, and O(X)-LDL-potentiated platelet activation than the control group;
      3) O(X)-LDL-potentiated platelet aggregation was enhanced by strenuous arm
      exercise in both groups, but the effect of exercise was more pronounced in the
      SCI group than in the control group; 4) treating the platelet with L-arginine
      inhibited O(X)-LDL-potentiated platelet activation in both groups. The study
      concludes that individuals with SCI had more extensive resting and exercise
      enhanced O(X)-LDL-potentiated platelet activation and greater amounts of
      preformed lipid peroxides than those without SCI. Therefore, supplementation
      therapy with antioxidants may be needed for patients with SCI, especially in a
      strenuous arm exercise period.

PMID- 10928482
TI  - Tissue factor is rapidly elevated in plasma collected from the pericardial cavity
      during cardiopulmonary bypass.
AB  - There is growing evidence that the tissue factor/factor VIIa pathway of
      coagulation is enhanced during cardiopulmonary bypass. Hitherto, available
      evidence has suggested that upregulated monocyte bound tissue factor is made
      available, either in the blood collected from the site of surgery or on
      circulating cells. However, cellular upregulation is slow, while generation of
      factor VIIa in blood collected from the pericardial cavity is rapid. We have
      therefore investigated the possibility of an alternative source of tissue factor,
      plasma (as opposed to cellular) tissue factor in blood samples taken from the
      central vein catheter (systemic circulation) and collected from the pericardial
      cavity during cardiopulmonary bypass. Six patients undergoing first time
      cardiopulmonary bypass grafting were studied. Tissue factor antigen was found to
      be rapidly elevated (by 15 min) in the pericardial plasma, approximately 5-fold
      above systemic levels (p <0.004). Similar elevations were found in markers of
      coagulation activation, factor VIIa antigen (p = 0.066), prothrombin fragment
      F(1+2) (p <0.003) and thrombin-antithrombin complex (p <0.03). To explore whether
      plasma tissue factor was (or had been) functionally active, factor VIIa was
      measured also with the soluble tissue factor functional assay after removal of
      heparin. Functional factor VIIa activity fell significantly in the systemic
      circulation, probably due to the heparin-induced increase (approximately 15-fold)
      in tissue factor pathway inhibitor (TFPI), but was elevated in pericardial blood
      compared with that taken from the central line catheter (p <0.006). These results
      demonstrate that both components of the activation complex for the extrinsic
      pathway of coagulation are rapidly generated in pericardial blood during bypass.

PMID- 10928483
TI  - Inhibition of tissue factor synthesis by disruption of ERK kinases and PKC
      signaling pathways in human vascular SMCs.
AB  - Tissue Factor (TF), the receptor for plasma VII/VIIa and the initiator of blood
      coagulation, is inducible in vascular smooth muscle cells (SMCs) by growth
      factors and bacterial lysopolysaccharides (LPS) and is expressed in vivo after
      vascular injury. As TF expression is a determinant of the thrombogenicity of
      vascular lesions, we investigated the signal pathways involved in this process.
      Human vascular SMCs were obtained from normal arteries and made quiescent by
      serum deprivation. Baseline TF antigen and activity were up-regulated by various
      agonists: fetal calf serum (FCS), LPS, and platelet derived growth factor (PDGF)
      being the most effective but with different kinetics. TF expression induced by
      LPS was transient with a maximum 6 h after stimulation and returned to baseline
      levels after 24 h whereas TF expression induced by serum or PDGF was sustained
      for at least 24 h. Rapid and transient activation of Extracellular signal
      Regulated Kinase (ERK) was observed after stimulation by PDGF and FCS, but not by
      LPS. The role of ERK, Ras and protein kinase C activities were investigated using
      specific inhibitors, PD 98059, manumycin A and calphostin C respectively. For TF
      induction by LPS, PKC activity was required and the ERK/Ras pathway was not
      involved. In contrast, the effect of PDGF was strictly ERK and Ras dependent, but
      partially prevented by PKC inhibitors. TF induction by FCS was ERK dependent but
      partially Ras and PKC dependent. In conclusion, TF expression appears to be a non
      specific response of SMCs to numerous stimuli through multiple signal pathways
      which differ according to the inducing agent.

PMID- 10928484
TI  - Genetic coronary risk factors in conventionally low-risk patients.

PMID- 10928486
TI  - Activated protein C (APC) resistance: considerations about the importance of
      using the original and modified methods in thrombophilic disease.

PMID- 10928485
TI  - Inter-assay and instrument variability of anti-Xa--results.

PMID- 10928487
TI  - Bleeding complications associated with low molecular weight heparin prophylaxis
      during pregnancy.

PMID- 10928488
TI  - Coagulation factor II activity determination is not useful as a screening tool
      for the G20210A prothrombin gene allele.

PMID- 10928489
TI  - G20210A prothrombin gene polymorphism and extent of coronary disease.

PMID- 10928490
TI  - Application of the TaqMan-PCR for genotyping of the prothrombin G20210A mutation
      and of the thermolabile methylenetetrahydrofolate reductase mutation.

PMID- 10928491
TI  - Transient inhibitors in the Recombinate PUP study.

PMID- 10928492
TI  - In memoriam: Timothy Scott-Burden.

PMID- 10928493
TI  - Predictors of gastrointestinal complications in cardiac surgery.
AB  - Gastrointestinal problems are infrequent but serious complications of cardiac
      surgery, with high rates of morbidity and mortality. Predictors of these
      complications are not well developed, and the role of fundamental variables
      remains controversial. In a retrospective review of our cardiac surgery
      experience from July 1991 through December 1997 we found that postoperative
      gastrointestinal complications were diagnosed in 86 of 4,463 consecutive patients
      (1.9%). We categorized these 86 patients into 2 groups--Surgical and Medical-
      according to the method of treatment used for their complications. In the Medical
      group, 9 of 52 patients (17%) died; in the Surgical group, 17 of 34 (50%) died.
      By logistic multivariate analysis, we identified 8 parameters that predicted
      gastrointestinal complications: age greater than 70 years, duration of
      cardiopulmonary bypass, need for blood transfusions, reoperation, triple-vessel
      disease, New York Heart Association functional class IV, peripheral vascular
      disease, and congestive heart failure. Postoperative re-exploration for bleeding
      was a predictor specific to the Surgical group. Use of an intraaortic balloon
      pump was markedly higher in the Gastrointestinal group than in the Control group
      (30% vs 10%, respectively), as was the use of inotropic support in the immediate
      postoperative period (27% vs 5.6%). Our results suggest that intra-abdominal
      ischemic injury is a likely contributing factor in most gastrointestinal
      complications. In turn, the ischemia is probably caused by hypoperfusion due to
      low cardiac output, hypotension due to blood loss, and intra-abdominal
      atheroemboli. The derived models are useful for identifying patients whose risk
      of gastrointestinal complications after cardiac surgery may be reduced by
      clinical measures designed to counter these mechanisms.

PMID- 10928494
TI  - Exercise hemodynamic findings in patients with exertional dyspnea.
AB  - To determine whether upright bicycle exercise could provide useful information
      about disabling exertional dyspnea in the absence of severe abnormalities (as
      shown by traditional testing methods), we evaluated 13 such patients. There were
      3 men and 10 women with a mean age of 49+/-15 (SD) years. We used pulmonary
      artery catheterization at rest and during upright bicycle exercise to evaluate
      these patients. All patients had normal left ventricular function except for 1,
      who had an ejection fraction of 45%. The mean duration to peak exercise was 9+/-6
      minutes. Normal systolic pulmonary artery pressure was defined as 25+/-5 mmHg.
      Four patients had normal systolic pulmonary pressure, and 9 exhibited pulmonary
      hypertension with exercise. In those 9, the mean mixed pulmonary venous oxygen
      saturation at rest was 61%+/-9% and fell to 32%+/-9% at peak exercise. Six of the
      9 patients also had some degree of resting pulmonary hypertension that worsened
      with exercise: their mean pulmonary artery systolic pressure at rest was 47+/-14
      mmHg and rose to 75+/-25 mmHg at peak exertion (P = 0.01). The other 3 patients
      showed no pulmonary hypertension at rest; their mean pulmonary artery systolic
      pressure was 27+/-6 mmHg. However, this level rose to 53+/-4 mmHg at peak
      exertion (P = 0.04). In this pilot study of patients with dyspnea, 9 of 13 (69%)
      displayed marked pulmonary hypertension with exercise. The resting hemodynamic
      levels were normal in 3 (33%) of those with exercise pulmonary hypertension. We
      conclude that hemodynamic data from bicycle exercise tests can provide additional
      information regarding the mechanisms of exertional dyspnea.

PMID- 10928495
TI  - A novel approach to coronary revascularization in patients with severely diseased
      aorta.
AB  - Atheromatous disease of the aorta significantly increases morbidity and mortality
      during coronary revascularization. The surgical approach must be modified for
      patients in whom this condition is identified. In this report, we describe a
      technique that uses bilateral internal thoracic arteries as composite grafts with
      reverse saphenous veins. The operation is performed without cardiopulmonary
      bypass. We report the cases of 2 patients who underwent this procedure. Neither
      patient experienced signs or symptoms of atheromatous embolization, and there was
      no perioperative morbidity or mortality. Off-pump myocardial revascularization
      using bilateral internal thoracic arteries is an attractive surgical approach for
      patients who have atheromatous aortas or other conditions in which it is
      advantageous to avoid aortic manipulation, cannulation, cross-clamping, and
      cardiopulmonary bypass.

PMID- 10928496
TI  - Atrial resection in advanced lung carcinoma under total cardiopulmonary bypass.
AB  - There are few reports of a surgical approach to T4 lung carcinoma that has
      invaded the heart. Although most cases will be considered inoperable, cases in
      which there is potential for complete resection and no distant or nodal
      metastatic disease (T4 N0 M0, Stage IIIB) may be considered for surgical therapy.
      We report a case of squamous cell carcinoma of the lung with cardiac involvement,
      in which we performed a completion pneumonectomy using total cardiopulmonary
      bypass. We describe indications and techniques for use of cardiopulmonary bypass
      in such cases.

PMID- 10928497
TI  - Yustin Y. Djanelidze and the first successful repair of an injured ascending
      aorta.
AB  - Yustin Y. Djanelidze is one of the little-known pioneers of cardiac surgery in
      the 20th century. He successfully sutured a penetrating injury of the ascending
      aorta in St. Petersburg, Russia, on 27 October 1913. To the best of our
      knowledge, this was the 1st case of ascending aorta repair described in the world
      medical literature.

PMID- 10928498
TI  - Endovascular treatment of peripheral vascular disease: a special section of the
      Texas Heart Institute Journal.

PMID- 10928499
TI  - State of the art: which stent for which lesion in peripheral interventions?
AB  - Applications of endovascular procedures have been expanded dramatically
      throughout the human body for both occlusive and aneurysmal disease; arteries at
      the aortoiliac and femoropopliteal levels are no exception. Currently,
      interventional procedures are the 1st treatment option for most patients who have
      peripheral artery disease. Although balloon angioplasty alone offers good
      immediate and long-term results, the addition of stents has been proposed to
      improve the procedural success of angioplasty and extend its application to more
      patients with vascular disease. Stenting, however, is controversial. Its use is
      considered acceptable in the aortoiliac vessels but is more in dispute for the
      femoropopliteal vessels. Moreover, the rapid development of endovascular stents
      for peripheral applications has made stent selection a complicated task for
      clinical practitioners. Many factors influence the type of stent selected;
      therefore, knowledge of the stents available--including various designs and
      individual properties--is mandatory. Appropriate selection depends on adequate
      preprocedural evaluation of the lesion; the choice of approach; the choice of
      primary versus selective stent placement; the location and characteristics of the
      lesion; the availability of stents in the intervention suite; and the experience
      of the operator Several stents are now available, but they are not equivalent; it
      is important to select the stent that is best suited to the lesion. On the basis
      of our experience using different types of stents, as well as our review of the
      world medical literature, we summarize the properties of various stents and
      specific indications for their application. This report is intended for use as a
      practical guide to stent selection.

PMID- 10928500
TI  - Early experience with the Talent stent-graft system for endoluminal repair of
      abdominal aortic aneurysms.

PMID- 10928501
TI  - Endovascular exclusion of abdominal aortic aneurysms: initial experience with
      stent-grafts in cardiology practice.
AB  - The use of an endovascular stent-graft prosthesis for the treatment of infrarenal
      abdominal aortic aneurysms is receiving increasing attention as an option that
      may avoid the significant morbidity and mortality associated with open surgical
      treatment. We studied the clinical effectiveness of stent-grafts in patients with
      infrarenal abdominal aortic aneurysms. Between October 1995 and May 1998, 33
      patients underwent infrarenal abdominal aortic aneurysm exclusion with a homemade
      polytetrafluoroethylene-covered stent, and between November 1998 and September
      1999, 56 patients underwent abdominal aortic aneurysm exclusion with the
      Medtronic AneuRx stent-graft. Overall, these patients represented a high-risk
      surgical group. The technical success rate was 100% in both groups. No patient
      required immediate conversion to open repair. With the polytetrafluoroethylene
      covered stent, the primary success rate was 33%, and the secondary success rate
      was 76%. In the AneuRx group, the primary success rate was 82.8%, and the
      secondary success rate was 85.3% at 6 months. There was no procedural or 1-month
      mortality or major morbidity in either group. By showing that infrarenal
      abdominal aortic aneurysms can be treated safely and successfully with an
      endoluminal stent-graft, our early results provide additional support for the
      endovascular treatment of abdominal aortic aneurysms. Further follow-up studies
      will determine the long-term ability of such treatment to prevent aneurysmal
      rupture and death.

PMID- 10928502
TI  - Regression of inflammatory abdominal aortic aneurysm after endoluminal treatment
      with bare-metal Wallstent endoprostheses.
AB  - Bare-metal Wallstent endoprostheses were used to treat a 60-year-old man who had
      an inflammatory abdominal aortic aneurysm, as confirmed by clinical and computed
      tomographic findings. The patient had concomitant coronary artery disease,
      congestive heart failure, chronic obstructive pulmonary disease, and severe
      iliofemoral disease. Because of high surgical risk due to coexisting disease
      (including severe peripheral vascular disease), the patient was not a candidate
      for current endovascular methods or surgical repair. Therefore, we used the novel
      endovascular approach described. Serial, spiral, computed tomographic scans
      during a 2-year follow-up period revealed a reduction in the maximal diameter of
      the abdominal aortic aneurysm from 44 mm to 36 mm. Stabilization of thrombus and
      regression of the periaortitis were also noted. To our knowledge, this is the 1st
      reported case of endoluminal therapy with an uncovered stent for an inflammatory
      abdominal aortic aneurysm. Bare-metal Wallstent exclusion of inflammatory
      abdominal aortic aneurysms presents a treatment option for patients who are at
      high risk for surgery and cannot be treated with covered stent-grafts due to
      severe disease of the iliofemoral vessels.

PMID- 10928504
TI  - Carotid stenting for post-endarterectomy restenosis and radiation-induced
      occlusive disease.
AB  - Surgical treatment of carotid restenosis and radiation-induced occlusive disease
      is challenging because of the high morbidity and mortality associated with this
      procedure. Carotid stenting has been proposed as an alternative approach. We
      report a series of 8 patients who were treated via the percutaneous approach for
      either carotid restenosis (n = 4) or radiation-induced occlusive disease (n = 4).
      Technical success was achieved in all of the cases. There have been no deaths or
      strokes during the periprocedural or follow-up period. After dilation of the
      extracranial vessel, 1 patient experienced severe intracranial internal carotid
      arterial spasm that required stent placement. Wallstents were used in 6 patients
      and S.M.A.R.T. stents were used in the remaining 2. Restenosis occurred in 2
      patients and was treated successfully with redilation or restenting. Carotid
      stenting appears to be a feasible and safe alternative to surgery for restenosis
      after carotid endarterectomy and for radiation-induced occlusive disease.

PMID- 10928503
TI  - Angioplasty and stenting of the extracranial carotid arteries.
AB  - We performed percutaneous transluminal angioplasty and stenting in patients with
      carotid artery stenosis to determine the efficacy of these techniques as an
      alternative to surgical endarterectomy. From April 1995 through July 1999, 315
      carotid angioplasty procedures were performed (right, 151; left, 164) in 290
      patients ranging in age from 40 to 93 years. Of these patients, 42% were
      symptomatic and 58% were asymptomatic. Twenty-five patients underwent bilateral
      procedures. The mean percentage of stenosis was 82.3%+/-8.7% SD. Angioplasty and
      stenting were performed without cerebral protection in 165 arteries and with
      protection in 150. Two methods of protection were used: the Theron technique and
      the PercuSurge Guardwire temporary occlusion and aspiration system. Balloon
      dilation and stent placement were successful in 289 patients; in the last
      patient, severe arterial tortuosity prevented catheterization and stenting. We
      observed 13 periprocedural neurologic complications due to ischemia (4.2%): 4
      transient ischemic attacks (1.3%), 4 minor strokes (1.3%), and 5 major strokes
      (1.6%), including 1 death. At 6 months, 210 patients had a follow-up angiogram
      (155) or duplex ultrasound (55). There were 10 restenoses (4.7%), 1 of which was
      symptomatic and 2 of which showed mild compression of a Palmaz stent without
      marked stenosis. Primary and secondary 4-year patency rates were 96% and 99%,
      respectively. These results demonstrate acceptable mortality and morbidity rates
      related to carotid angioplasty and stenting. However, we found the risk of
      embolic stroke to be substantial. Cerebral protection may improve the results of
      carotid angioplasty and expand the indications for this procedure.

PMID- 10928505
TI  - Tandem stenting of crossed renal arteries with ostial stenosis.
AB  - Ostial stenosis of renal arteries has been shown to respond favorably to
      stenting. Heterogeneity of renal artery anatomy is very common and often
      increases the technical difficulty of percutaneous treatment of stenotic lesions.
      We present the case of a 69-year-old man with severe hypertension who had 2 right
      renal arteries, both of which had ostial stenosis. We treated these stenoses with
      simultaneous stenting of both renal ostia. Since the procedure, the patient has
      had significantly improved control of his hypertension.

PMID- 10928507
TI  - Neonatal arterial switch operation for transposition of the great arteries in a
      patient with mirror image dextrocardia and situs inversus totalis.
AB  - The neonatal arterial switch operation has become the standard therapy for D
      transposition of the great arteries in the absence of left ventricular outflow
      tract obstruction. We describe our experience of successful arterial switch
      operation after balloon atrial septostomy in a 5-day-old infant girl who had
      atrial and visceral situs inversus totalis, mirror image dextrocardia, and D
      transposition of the great arteries. To our knowledge, ours is the first report
      of this operation in a patient with this anatomy.

PMID- 10928506
TI  - Current concepts in the evaluation of vascular disease: magnetic resonance and
      computed tomographic angiography.

PMID- 10928508
TI  - Angiogenesis in a patient with ischemic limb induced by intramuscular injection
      of vascular endothelial growth factor and fibrin platform.
AB  - Direct revascularization of critical ischemia of the limb is often unsuccessful
      due to the anatomic extent and distribution of arterial occlusive disease, and no
      pharmacologic treatment has proved effective in treating this condition. Patients
      with ischemic limb may eventually require amputation and may develop serious
      morbidity and mortality. The goal of limb salvage in these patients has
      stimulated research into alternative treatment methods, including angiogenesis.
      Attempts have been made to apply growth factors directly or to encode DNA for
      such factors, but it is unknown whether these factors remain at the target site
      long enough to be effective. We report our strategy of using vascular endothelial
      growth factor in a fibrin network, which enables the sustained release of
      biologic material at the target site.

PMID- 10928510
TI  - Primary cardiac rhabdomyosarcoma of the left atrium: an unusual presentation.
AB  - Rhabdomyosarcoma accounts for almost 20% of all primary malignant neoplasms of
      the heart. These tumors usually arise from the ventricular walls. In adult
      patients, they sometimes arise from the atrial walls and mimic atrioventricular
      valve stenosis. We describe a case of left atrial rhabdomyosarcoma that presented
      as severe mitral stenosis and required emergency surgery. The atrial mass was
      detected by transthoracic and transesophageal echocardiography, but only
      histopathology confirmed the nature of the lesion. Although rhabdomyosarcomas of
      the heart are highly lethal, operation is indicated for emergency cases, in order
      to clarify the diagnosis, relieve symptoms, and improve short-term survival.

PMID- 10928509
TI  - Tricuspid aortic valve with partial commissural fusion: prelminary report of an
      apparently common cause of aortic ejection sounds with potential for serious
      sequelae, illustrated by two cases.
AB  - We report the cases of 2 patients whose tricuspid aortic valves were found to
      have partial commissural fusion. Both patients experienced complications that
      were probably related to this abnormality: bacterial endocarditis in 1 instance
      and a lacunar stroke in the other. In order to illustrate the similarity of
      physical findings, we also describe the case of a 3rd patient, who had a typical
      bicuspid aortic valve. Tricuspid aortic valve with partial commissural fusion has
      been described in autopsy series and has been predicted to cause an ejection
      sound, but we could find no previously published description of this lesion in
      living patients. We wish to alert others to the possible presence of aortic
      commissural fusion, to its potential for serious and likely preventable sequelae,
      and to the ability of carefully performed transthoracic high-resolution digital
      echocardiography to demonstrate this condition when its characteristics are found
      on physical examination.

PMID- 10928511
TI  - Primary vascular echinococcosis: an uncommon cause of chronic iliofemoral
      arterial occlusion.
AB  - We report the case of a 33-year-old woman who was admitted to our clinic with the
      diagnosis of chronic arterial occlusion of the right lower extremity.
      Preoperative angiography suggested an iliofemoral atherosclerotic occlusion.
      During surgery multiple hydatid cysts causing iliofemoral occlusion were found
      and excised. Arterial reconstruction was performed using an iliofemoral bypass
      technique with a polytetrafluoroethylene vascular graft. This case emphasizes
      that, in sheep-raising countries or in patients from such countries, primary
      vascular echinococcosis should be considered in the differential diagnosis of
      chronic arterial occlusion.

PMID- 10928512
TI  - Intravenous atropine relieves coronary arterial spasm and hemodynamic
      decompensation during recovery after exercise.
AB  - A 66-year-old man developed right coronary arterial spasm and hemodynamic
      decompensation during the early recovery phase of a treadmill exercise test. The
      unstable condition was corrected immediately after intravenous administration of
      atropine. A subsequent coronary angiographic study revealed insignificant right
      coronary artery stenosis. The pathophysiology of this response may be related to
      rapid alterations in autonomic balance during recovery after exercise. To our
      knowledge, this is the 1st reported case in which atropine effected immediate
      reversal of coronary arterial spasm and hemodynamic decompensation that were
      induced by exercise, rather than by pharmacologic agents. Atropine might be an
      effective treatment in patients who experience exercise-induced coronary arterial
      spasm and hemodynamic decompensation, but further investigation is warranted.

PMID- 10928513
TI  - Combined percutaneous atrial septal defect occlusion and pulmonary balloon
      valvuloplasty in adult patients.
AB  - Severe pulmonary stenosis in association with a large atrial septal defect is
      uncommon. When these 2 conditions are present, significant left-to-right shunt is
      often prevented by the outflow obstruction, which protects the pulmonary bed
      until adulthood. This report shows our initial experience of percutaneous
      treatment of both congenital malformations, either staged or combined in the same
      procedure, in 2 adult patients whose treatments yielded effective atrial septal
      defect occlusion and right ventricular pressure relief that persisted at mid-term
      follow-up. Although these opposite procedures (opening and closing) have been
      applied as isolated methods of treatment, this preliminary experience appears to
      demonstrate the feasibility and effectiveness of a combined percutaneous
      treatment.

PMID- 10928514
TI  - Cardiac involvement in neurofibromatosis.

PMID- 10928515
TI  - Coronary artery-right atrium fistula.

PMID- 10928516
TI  - Pediatric intervention: an update--part II.

PMID- 10928517
TI  - Endovascular management of iliac vein compression (May-Thurner) syndrome.
AB  - PURPOSE: To evaluate the feasibility of endovascular techniques in treating
      venous outflow obstruction resulting from compression of the iliac vein by the
      iliac artery of the left lower extremity (May-Thurner syndrome). MATERIALS AND
      METHODS: A retrospective analysis of 39 patients (29 women, 10 men; median age,
      46 years) with iliac vein compression syndrome (IVCS) was performed. Nineteen
      patients presented with acute deep vein thrombosis (DVT) and 20 patients
      presented with chronic symptoms. All patients presented with leg edema or pain.
      In the acute group, patients were treated with catheter-directed thrombolysis
      (120,000-180,000 IU urokinase/h) and angioplasty followed by stent placement. In
      the chronic group, patients were treated with use of angioplasty and stent
      placement alone (n = 8), or in combination with thrombolysis (n = 12). Patients
      were then followed-up with duplex ultrasound and a quality-of-life assessment.
      RESULTS: Initial technical success was achieved in 34 of 39 patients (87%). The
      overall patency rate at 1 year was 79%. Symptomatically, 85% of patients were
      completely or partially improved compared with findings before treatment. Thirty
      five of 39 patients received stents. The 1-year patency rate for patients with
      acute symptoms who received stents was 91.6%; for patients with chronic symptoms
      who received stents, the 1-year patency rate was 93.9%. Five technical failures
      occurred. Major complications included acute iliac vein rethrombosis (< 24 hours)
      requiring reintervention (n = 2). Minor complications included perisheath
      hematomas (n = 4) and minor bleeding (n = 1). There were no deaths, pulmonary
      embolus, cerebral hemorrhage, or major bleeding complications. CONCLUSION:
      Endovascular reconstruction of occluded iliac veins secondary to IVCS (May
      Thurner) appears to be safe and effective.

PMID- 10928518
TI  - Venous thrombosis related to peripherally inserted central catheters.
AB  - PURPOSE: To determine factors that may lead to venous thrombosis in patients with
      peripherally inserted central catheters (PICC). MATERIALS AND METHODS: The
      medical records of 678 patients with 813 PICCs during 1997 were cross-referenced
      with all patients receiving venous duplex examinations (1,631) during the same
      time period. Multiple factors were examined in the patients with catheter-related
      thrombosis, including diagnosis, solution infused, catheter tip position, vein
      accessed, and catheter diameter. RESULTS: Nurses placed 269 PICCs with 12 venous
      thromboses, for a rate of 4.5%. Radiologists placed 544 PICCs with 20 venous
      thromboses, for a rate of 3.7%. There was no significant difference in these
      rates. The overall thrombosis rate was 3.9%. After multivariate analysis, only
      catheter diameter remained significant. There were no thromboses in catheters 3 F
      or smaller. The thrombosis rate was 1% for 4-F catheters, 6.6% for 5-F catheters,
      and 9.8% for 6-F catheters. CONCLUSIONS: Thrombosis rate associated with PICCs
      was low (3.9%). The smallest acceptable catheter diameter should be used to
      decrease the incidence of venous thrombosis.

PMID- 10928519
TI  - The case of Abbokinase and the FDA: the events leading to the suspension of
      Abbokinase supplies in the United States.

PMID- 10928520
TI  - Reteplase in the treatment of peripheral arterial and venous occlusions: a pilot
      study.
AB  - PURPOSE: Reteplase, a truncated mutant of tissue plasminogen activator, has been
      used successfully in the treatment of acute coronary occlusion, but, heretofore,
      it has not been investigated in the setting of peripheral vascular occlusion.
      Reteplase is a potential recombinant thrombolytic agent that may offer an
      appropriate alternative to currently employed plasminogen activators. MATERIALS
      AND METHODS: Over a 6-month period reteplase was used to treat peripheral
      vascular occlusions at five centers in the United States. The agent was used in
      peripheral arterial occlusion (n = 26, 70.3%) or venous occlusion (n = 11,
      29.7%), in doses ranging from 0.5 to 2.0 U/h, infused directly into the thrombus.
      A lacing dose (4.3 +/- 0.9 U) was employed in 17 patients (45.9%), and 25
      patients (67.6%) received concurrent heparin therapy in a subtherapeutic dose (n
      = 14, 37.8%) or as full therapeutic anticoagulation (n = 11, 29.7%). RESULTS: The
      26 patients with arterial occlusions received a total dose of reteplase that
      averaged 20.5 U +/- 5.3 (mean +/- SEM), ranging from 3.5 to 82 U. The duration of
      infusion was 19.3 hours +/- 2.4 with a range of 0.2-36 hours. Complete
      dissolution of the occluding thrombus was achieved in 23 patients (88.5%).
      Hemorrhagic complications developed in eight patients (30.8%) and were major in
      five patients (19.2%). No patient experienced intracranial bleeding. Although
      there was no association between the dose regimen and thrombolytic efficacy,
      bleeding complications appeared to be more frequent as the dose was increased
      from 0.5 to 2.0 U/h. The 11 patients treated for deep venous thrombi received an
      average of 32.6 U +/- 7.4 of reteplase, ranging from 6 to 75 U over a mean length
      of time of 31.1 hours +/- 7.3 (range, 4-84 hours). Complete dissolution of
      thrombus occurred in eight patients (72.7%). Hemorrhagic complications developed
      in three patients (27.3%) and one of the episodes was major (9.1%). No patient
      experienced intracranial hemorrhage. CONCLUSIONS: Reteplase appears to be an
      acceptable alternative thrombolytic agent with a satisfactory safety and efficacy
      profile in the setting of peripheral arterial and venous occlusion. As such, it
      may provide an attractive alternative for the treatment of peripheral arterial
      and venous thrombotic occlusions. However, definitive conclusions must await the
      results of controlled comparisons of reteplase to other thrombolytic agents.

PMID- 10928521
TI  - Fatal outcome after embolotherapy for hepatic arteriovenous malformations of the
      liver in two patients with hereditary hemorrhagic telangiectasia.

PMID- 10928522
TI  - Ovarian vein embolization for the treatment of pelvic congestion syndrome: long
      term technical and clinical results.
AB  - PURPOSE: Ovarian vein embolization has been used recently to treat pelvic
      congestion syndrome. The purpose of this study is to evaluate the clinical
      efficacy and safety of ovarian vein embolization in the treatment of symptomatic
      pelvic varices. MATERIALS AND METHODS: We performed ovarian vein embolization in
      41 patients (mean age, 37.8 years; range, 30-58 years): 32 patients underwent
      unilateral embolization and nine patients underwent bilateral embolization. All
      had lower abdominal pain and pelvic varicosities were found on retrograde ovarian
      vein venography. Embolization was performed with a mixture of enbucrilate and
      lipiodized oil in all but one patient, in whom enbucrilate and minicoils were
      used. Initial technical success rate and clinical follow-up (1-61 months; mean,
      19.9 months), conducted with use of mailed questionnaires, are reported. RESULTS:
      Initial technical success rate was 98%. Immediate complications were noted in two
      patients (4%) in the form of migration of some fragments of glue (used as embolic
      agent), which was treated conservatively. Clinical follow-up reveals variable
      symptomatic relief in 9.7% of cases and a total relief of symptoms in 58.5% of
      cases. Results in patients who had insufficient ovarian veins bilaterally were no
      better than those in patients for whom only the left ovarian vein was found
      insufficient. CONCLUSIONS: Transcatheter embolization of the ovarian veins is a
      safe and feasible technique leading to complete relief of symptoms in more than
      half of cases. No statistically significant difference in clinical outcome could
      be noted between patients presenting with bilateral insufficient ovarian veins,
      who underwent bilateral embolization, and patients presenting with an
      insufficient left ovarian vein, who underwent left unilateral embolization.

PMID- 10928523
TI  - Coil embolization of segmental arterial mediolysis of the hepatic artery.

PMID- 10928524
TI  - Mesenteric angiography in the diagnosis of volvulus.

PMID- 10928525
TI  - Balloon tamponade for the treatment of inadvertent subclavian arterial catheter
      placement.

PMID- 10928527
TI  - Treatment of caliceal diverticular stones: transdiverticular percutaneous
      nephrolithotomy with creation of a neoinfundibulum.
AB  - PURPOSE: To evaluate transdiverticular percutaneous nephrolithotomy (TDPN) with
      creation of a neoinfundibulum in the treatment of caliceal diverticular stones.
      PATIENTS AND METHODS: Between 1990 and 1998, 18 patients with symptomatic calculi
      in caliceal diverticula underwent TDPN. Transdiverticular puncture into the renal
      collecting system with creation of a neoinfundibulum was used, eliminating the
      need for prolonged probing with a wire for the neck of the diverticulum. Eight
      diverticula were upper polar, six were interpolar, and four were in the lower
      pole. Stones were endoscopically treated with use of Lithoclast (Electromedical
      Systems, Lausanne, Switzerland), graspers, ultrasound, or a combination of these
      methods. RESULTS: Sixteen kidneys (89%) were rendered stone-free at discharge.
      Two kidneys (11%) were left with stone fragments of 5 mm or smaller. Hospital
      stay ranged from 3 to 15 days (average, 7 days). Procedure time ranged from 45 to
      169 minutes (average, 87 minutes). One patient developed a left renal-pleural
      fistula, which closed 1 week after chest tube drainage. No other complications
      were encountered for an overall complication rate of 6%. CONCLUSION: TDPN is a
      safe and effective method for treating caliceal diverticular stones, with a
      complication rate comparable to other methods.

PMID- 10928526
TI  - Value of CT fluoroscopy for percutaneous biopsy procedures.
AB  - PURPOSE: To assess the clinical impact of computed tomographic (CT) fluoroscopy
      (CTF) with regard to procedure time and success rate for CT image-guided biopsy
      procedures. MATERIALS AND METHODS: One hundred ninety consecutive patients
      referred to the same radiologist underwent biopsy procedures performed with use
      of a CT scanner equipped with fluoroscopic capabilities during a 15-month period.
      CTF procedures were performed predominantly by means of a continuous fluoroscopic
      technique, with typical exposure factors of 50 mA at 120 kV and a slice thickness
      of 10 mm. The total procedure time, fluoroscopy time, and complication and
      procedure success rates were documented prospectively in this group. A control
      group consisted of retrospective analysis of 93 consecutive patients who had
      undergone a classic CT-guided procedure performed by the same radiologist.
      RESULTS: Procedure success rate was increased in the CTF group (93.7 versus
      88.2%), although the difference was not statistically significant (P > .05:
      Fisher exact test). A statistically significant difference was noted when
      comparing mean procedure times (CTF, 27.56 minutes; range, 20-60 minutes versus
      control, 43.17 minutes; range, 35-80 minutes; P < .0001; Welch unpaired t test).
      CONCLUSION: CT fluoroscopy facilitates CT-guided biopsy procedures by allowing
      visualization of the needle trajectory from skin entry to the target point,
      allowing procedures to be performed more rapidly and efficiently.

PMID- 10928528
TI  - Patient tolerance of cervical esophageal metallic stents.
AB  - PURPOSE: To demonstrate that proximal esophageal stenoses and tracheoesophageal
      fistulas can be adequately palliated with use of metallic stents without
      significant foreign-body sensation. MATERIALS AND METHODS: Between June 1994 and
      March 1999, 22 patients with lesions within 3 cm of the cricopharyngeus were
      treated by placement of metallic stents. The series was reviewed retrospectively.
      Twenty patients had surgically unresectable malignant lesions, two patients had
      benign disease. Ten patients had associated tracheoesophageal fistulas. In all,
      the upper limit of the stent was between C5 vertebral body inferior endplate and
      the T2 vertebral body superior endplate. The case-notes were reviewed until
      patient death (range, 6-198 days), or to date in the two surviving patients with
      benign disease. RESULTS: Immediate technical success was 93% (27 of 29).
      Dysphagia scores improved from a median of 3 to 2 after stent placement. Eighteen
      of 22 (82%) patients reported no foreign-body sensation. There have been no cases
      of proximal migration, periprocedural perforation, or deaths. The two patients
      with benign disease experienced significant complications. CONCLUSION: Lesions in
      proximity to the cricopharyngeus can be successfully palliated without
      significant foreign-body sensation in the majority of patients with use of
      metallic stents. The authors urge caution in placing stents in patients with
      benign disease.

PMID- 10928529
TI  - A simple method for the placement of non-endhole jejunal feeding tubes: a
      modified monorail technique.

PMID- 10928530
TI  - Duodenal perforation as a delayed complication of placement of an esophageal
      stent.

PMID- 10928531
TI  - Use of fibrin sealant as a hemostatic agent after liver biopsy in swine.
AB  - PURPOSE: To determine whether fibrin sealant injected into the tract created by
      liver biopsy can be used to decrease postprocedural bleeding. An innovative
      delivery system was used to deploy the fibrin sealant. MATERIALS AND METHODS:
      Fibrin sealant is a hemostatic agent consisting of a suspension of fibrinogen and
      thrombin. A delivery system was devised whereby fibrin sealant could be injected
      into the tract created by liver biopsy. Thirty swine were randomized into three
      groups: control (n = 10), heparin (n = 10), and warfarin (n = 10). Each swine
      underwent laparotomy and was randomized to undergo three to five open liver
      biopsies with either a 14-gauge cutting needle in conjunction with the fibrin
      sealant device or a standard 14-gauge cutting needle alone. Forty-seven biopsy
      procedures were performed with the device; 64 biopsy procedures were performed
      without the device. Immediate blood loss per biopsy (mL) was estimated based on
      the size of the blood stain on a sponge. Specimens were assessed for sample size.
      RESULTS: Immediate blood loss with and without the device, respectively, was:
      control, 0.1 mL, 5.4 mL; heparin, 0 mL, 7 mL; warfarin, 0.1 mL, 9.3 mL. These
      differences were significant (P < .01) for each group of swine. In 43 of 47
      biopsies (91%), the device functioned without difficulty. There was no difference
      in sample size when the device was used. CONCLUSIONS: The fibrin sealant device
      is effective in reducing bleeding after open liver biopsy in anticoagulated and
      nonanticoagulated swine. The promising results suggest that a trial of
      percutaneous liver biopsy in swine should be considered.

PMID- 10928532
TI  - Hepatic perfusion before and after the transjugular intrahepatic portosystemic
      shunt procedure: impact on survival.
AB  - PURPOSE: This study correlates transjugular intrahepatic portosystemic shunt
      (TIPS) mortality with flow patterns in the cirrhotic liver. MATERIALS AND
      METHODS: Twenty-seven TIPS patients and 10 control subjects were used for this
      study. The authors evaluated hepatic perfusion with venous injections of Tc-99m
      pertechnetate before and after TIPS. Hepatic time-activity curves were analyzed
      for type and amount of liver perfusion. These parameters were correlated with
      survival for a mean follow-up of 18 months. RESULTS: The mean arterial
      contribution to liver blood flow was 25.4% in the normal control patients, 39.9%
      in patients prior to TIPS, and increased to 48.3% after TIPS. Although the
      proportion of arterial supply to the cirrhotic liver varied widely, TIPS
      mortality did not correlate with the preprocedure hepatic artery/portal venous
      perfusion ratio. However, patients with both an "arterialized" flow pattern and
      low total hepatic perfusion had higher mortality, with a mean survival of 2
      months compared to patients with a more favorable perfusion profile (mean
      survival, 28.4 months). CONCLUSIONS: The proportion of arterial perfusion to the
      liver before TIPS did not affect survival. However, patients with a combination
      of reduced total hepatic perfusion and an arterial flow pattern had poorer
      survival, suggesting that both the quantity and quality of hepatic perfusion
      predicts TIPS outcome.

PMID- 10928533
TI  - Treatment of refractory benign biliary stenoses in liver transplant patients by
      placement and retrieval of a temporary stent-graft: work in progress.
AB  - PURPOSE: To evaluate patency of refractory benign biliary strictures in liver
      transplant patients treated with retrievable stent-grafts. MATERIALS AND METHODS:
      Eight male liver transplant patients who ranged in age from 42 to 52 years
      developed nine symptomatic biliary strictures (intrahepatic left duct, 1; hilar,
      2; anastomotic, 6). These strictures had recurred despite multiple previous
      attempts of treatment (n = 33), including angioplasty (n = 27), surgery (n = 1),
      atherectomy (n = 1), metallic stent (n = 1), and prolonged catheter drainage (n =
      3). As an alternative method of treatment for these refractory biliary
      strictures, transhepatic placement of expanded polytetrafluoroethylene stent
      grafts across the strictures was performed through 10-F sheaths. In total, 14
      stent-grafts were placed to treat the nine lesions, and nine of these stent
      grafts were subsequently retrieved through 12-16-F sheaths. RESULTS: Stent-grafts
      were deployed successfully. Delayed migrations in two patients required
      additional stent-graft placement. One patient died of pneumonia 1 month after
      stent-graft placement; the remaining seven patients had stent-grafts successfully
      removed at 3-10 months (mean, 5.6 months). Nine intended stent-graft retrievals
      were performed successfully, with two requiring use of elongated forceps.
      Immediately after treatment, all strictures were widely patent. Five to 6 months
      after stent-graft removal in these seven patients, significant strictures
      recurred in four of eight lesions (50%). One patient underwent surgical revision.
      At 6-29 months (mean, 12 months) after stent-graft removal, the remaining six
      patients were without clinical or laboratory evidence of biliary obstruction,
      despite three patients with significant recurrent strictures. CONCLUSION:
      Temporary stent-graft placement for treatment of benign biliary strictures in
      liver transplant patients is technically feasible. Longer follow-up with larger
      patient series is necessary to assess effectiveness and possible broader
      applications.

PMID- 10928535
TI  - Selective vessel catheterization technique: a dying art?

PMID- 10928534
TI  - Percutaneous deployment of a valved bovine jugular vein in the swine venous
      system: a potential treatment for venous insufficiency.
AB  - PURPOSE: To develop a system for potential use in the treatment of chronic venous
      insufficiency by using percutaneous techniques. MATERIALS AND METHODS: A segment
      of a glutaraldehyde-fixed bovine external jugular vein with valves was trimmed
      and sutured to a nitinol stent. Animals were premedicated and anesthetized (n =
      11). Venography of the right external jugular vein, inferior vena cava (IVC), and
      common iliac vein was performed. Deployment was accomplished via a sheath (12-24
      F) with use of fluoroscopic guidance. Eleven bioprostheses were deployed in 11
      animals. Bioprostheses were deployed in the IVC (n = 3) or right external iliac
      vein (n = 6). Animals were killed immediately after deployment (n = 7) at 1 week
      (n = 1) or at 2 weeks (n = 2). One animal was found dead in the cage. At
      necropsy, each bioprosthesis (n = 4) was explanted and histopathologic analysis
      was performed. RESULTS: Deployments of the bioprostheses were successful in nine
      of 11 swine. Two deployments were unsuccessful (one accidental deployment in the
      right renal vein, one deployment in the IVC caused rupture of the vein).
      Postdeployment venography (n = 9) confirmed no reflux (in the recumbent position
      of the swine) of the valve leaflets and patency of the vein inferior to the level
      of the bioprostheses. in the first group of animals (n = 5), valve leaflets were
      normal and competent. In the survival animal group (n = 4), the bioprostheses
      remained patent without evidence of thrombus formation by ascending and
      descending venography. Gross inspection of the explanted bioprostheses (n = 4)
      demonstrated grossly normal valves that fully occluded the lumen. Complications
      included hemarthrosis (n = 1), death (n = 1), and bioprosthesis thrombosis
      immediately after deployment (n = 1). Histopathologic analysis showed endothelial
      cells covering the luminal surfaces. The wall of the bioprostheses had
      granulomatous response and foreign body reaction. Bacterial contamination was
      noted in one bioprosthesis. CONCLUSIONS: Deployment of a glutaraldehyde-fixed
      bovine vein sutured to a self-expanding nitinol stent in the swine iliac vein or
      IVC is technically feasible. Development of a venous bioprosthesis that can be
      placed percutaneously may have important clinical applications as an endovascular
      treatment for chronic venous insufficiency when it is due to valvular
      incompetence.

PMID- 10928536
TI  - Precise placement of tract anesthesia for percutaneous biliary drainage and
      nephrostomy.

PMID- 10928538
TI  - Epicuticular waxes and flavonol aglycones of the European mistletoe, Viscum album
      L.
AB  - Cuticular waxes of Viscum album ssp. album contain oleanolic acid as main
      constituent, accompanied by aliphatic compounds like alkanes, esters and primary
      alcohols. A number of flavonol aglycones (methyl ethers of quercetin and
      kaempferol) have also been identified. Seasonal changes in amount and composition
      of cuticular waxes and the presence of flavonol aglycones are described and the
      ecophysiological significance of flavonoids on the surface of the mistletoe is
      briefly discussed.

PMID- 10928539
TI  - New constituents of the leaf and stem exudate of Ozothamnus hookeri (Asteraceae).
AB  - The exudate of Ozothamnus hookeri has been investigated for its non-flavonoid
      constituents. A new natural C6-C3 ester of a long chain fatty acid and seven
      structurally related kaurane-diterpenoids were isolated. Three of the latter are
      new natural products, too. A rare 8-methoxy flavonol was also identified.

PMID- 10928537
TI  - The non-mevalonate isoprenoid biosynthesis of plants as a test system for new
      herbicides and drugs against pathogenic bacteria and the malaria parasite.
AB  - Higher plants and several photosynthetic algae contain the plastidic 1-deoxy-D
      xylulose 5-phosphate/2-C-methyl-D-erythritol 4-phosphate pathway (DOXP/MEP
      pathway) for isoprenoid biosynthesis. The first four enzymes and their genes are
      known of this novel pathway. All of the ca. 10 enzymes of this isoprenoid pathway
      are potential targets for new classes of herbicides. Since the DOXP/MEP pathway
      also occurs in several pathogenic bacteria, such as Mycobacterium tuberculosis,
      and in the malaria parasite Plasmodium falciparum, all inhibitors and potential
      herbicides of the DOXP/MEP pathway in plants are also potential drugs against
      pathogenic bacteria and the malaria parasite. Plants with their easily to handle
      DOXP/MEP-pathway are thus very suitable test-systems also for new drugs against
      pathogenic bacteria and the malaria parasite as no particular security measures
      are required. In fact, the antibiotic herbicide fosmidomycin specifically
      inhibited not only the DOXP reductoisomerase in plants, but also that in bacteria
      and in the parasite P. falciparum, and cures malaria-infected mice. This is the
      first successful application of a herbicide of the novel isoprenoid pathway as a
      possible drug against malaria.

PMID- 10928540
TI  - An exceptionally large pyoverdin from a Pseudomonas strain collected in Thailand.
AB  - From a Pseudomonas strain obtained from a soil sample collected in Thailand a
      pyoverdin was obtained containing twelve amino acids in its peptide chain. The
      structure elucidation is described.

PMID- 10928541
TI  - Achromobactin, a new citrate siderophore of Erwinia chrysanthemi.
AB  - The structure of a citrate siderophore named achromobactin isolated from the
      culture medium of Erwinia chrysanthemi was elucidated by spectroscopic methods
      and chemical degradation.

PMID- 10928542
TI  - Isoangoroside C, a phenylpropanoid glycoside from Scrophularia scorodonia roots.
AB  - A new phenylpropanoid glycoside isoangoroside C was isolated from the roots of
      Scrophularia scorodonia. Its structure was determined on the basis of spectral
      data as: 3-hydroxy-4-methoxy-beta-phenylethoxy-O-alpha-L-arabinopyranosy l-(1-
      >6)alpha L-rhamnopyranosyl-(1-->3)-4-O-Z-feruloyl-beta-D-glucopyranoside.
      Additionally, one known phenylpropanoid, angoroside C, and five known iridoid
      glycosides, harpagoside, bartsioside, 8-O-acetyl-harpagide, aucuboside and
      harpagide were isolated and identified.

PMID- 10928543
TI  - A new flavone O-glycoside and other constituents from wheat leaves (Triticum
      aestivum L.).
AB  - From leaves of Triticum aestivum a new O-glycosylflavone has been isolated
      together with chlorogenic acid and its 3'-methyl ether and 6 C-glycosylflavones.
      The structure of the new flavonoid was determined by 1D and 2D NMR techniques and
      other spectral evidence as 5,7-dihydroxy-3',4',5'-trimethoxyflavone-7-O-beta
      rutinoside.

PMID- 10928544
TI  - Oxidative metabolism of ambrox and sclareolide by Botrytis cinerea.
AB  - Ambrox (1), a perfumery diterpene, was oxidatively metabolised by a plant
      pathogenic fungus Botrytis cinerea in a xenobiotic fashion to afford a major
      product, i.e., 1beta-hydroxy-8-epiambrox (13) (60%) along with three minor
      metabolites 3beta-hydroxyambrox (2), sclareolide (5) and 3beta-hydroxysclareolide
      (7). Sclareolide (5), a cytotoxic diterpenoidal lactone was fermented with the
      same fungus to yield 3beta-hydroxysclareolide (7) (59%) as a major metabolite
      together with two minor metabolites characterised as 1-ketosclareolide (15), and
      3beta,14-dihydroxysclareolide (16).

PMID- 10928545
TI  - Metal binding to Pseudomonas aeruginosa azurin: a kinetic investigation.
AB  - The interaction between azurin from Pseudomonas aeruginosa and Ag(I), Cu(II),
      Hg(II), was investigated as a function of protein state, i.e. apo-, reduced and
      oxidised azurin. Two different metal binding sites, characterized by two
      different spectroscopic absorbancies, were detected: one is accessible to Ag(I)
      and Cu(II) but not to Hg(II); the other one binds Ag(I) and Hg(II) but not
      copper. When added in stoichiometric amount, Ag(I) shows high affinity for the
      redox center of apo-azurin, to which it probably binds by the -SH group of
      Cys112; it can displace Cu(I) from reducedazurin, while it does not bind to the
      redox center of oxidizedazurin. Kinetic experiments show that Ag(I) binding to
      the reduced form is four times faster than binding to the apo-form. This result
      suggests that metal binding requires a conformational rearrangement of the active
      site of the azurin. Interaction of Ag(I) or Hg(II) ions to the second metal
      binding site, induces typical changes of UV spectrum and quenching of
      fluorescence emission.

PMID- 10928546
TI  - Bacteriorhodopsin thermal stability: influence of bound cations and lipids on the
      intrinsic protein fluorescence.
AB  - Temperature-induced changes in protein intrinsic fluorescence of native,
      delipidated and deionized purple membranes are investigated. It is found that the
      removal of cations most strongly affects the protein and its thermal stability.
      The denaturation of dei-BR completes at 70 degrees C, while delipidated and
      native BR still maintain their native structure at this temperature. Both the
      quantum yield and the fluorescence maximum suggest correlation between the Trp
      retinal coupling and protein structural stability. The low red shift of the
      fluorescence maximum caused by increasing of temperature indicates limited
      unfolding of bacteriorhodopsin upon denaturation.

PMID- 10928547
TI  - Photoinactivation and protection of glycolate oxidase in vitro and in leaves.
AB  - Glycolate oxidase that was partially purified from pea leaves was inactivated in
      vitro by blue light in the presence of FMN. Inactivation was greatly retarded in
      the absence of O2. Under aerobic conditions H2O2 was formed. The presence of
      catalase, GSH or dithiothreitol protected glycolate oxidase against
      photoinactivation. Less efficient protection was provided by ascorbate,
      histidine, tryptophan or EDTA. The presence of superoxide dismutase or of
      hydroxyl radical scavengers had no, or only minor, effects. Glutathione
      suppressed H2O2 accumulation and was oxidized in the presence of glycolate
      oxidase in blue light. Glycolate oxidase was also inactivated in the presence of
      a superoxide-generating system or by H2O2 in darkness. In intact leaves
      photoinactivation of glycolate oxidase was not observed. However, when catalase
      was inactivated by the application of 3-amino-1,2,4-triazole or depleted by
      prolonged exposure to cycloheximide a strong photoinactivation of glycolate
      oxidase was also seen in leaves. In vivo blue and red light were similarly
      effective. Furthermore, glycolate oxidase was photoinactivated in leaves when the
      endogenous GSH was depleted by the application of buthionine sulfoximine. Both
      catalase and antioxidants, in particular GSH, appear to be essential for the
      protection of glycolate oxidase in the peroxisomes in vivo.

PMID- 10928548
TI  - Beta-1,3-glucooligosaccharide induced activation of four enzymes responsible for
      N-p-coumaroyloctopamine biosynthesis in potato (Solanum tuberosum cv.) tuber
      tissue.
AB  - Potato tuber disks, when treated with laminarin, a beta-1,3-glucooligosaccharide
      from Laminaria digitata, accumulate a hydroxycinnamoyl amide compound, N-p
      coumaroyloctopamine (p-CO). The biosynthesis of p-CO was investigated by feeding
      experiments, in order to show that the precursors of N-p-coumaroyl and octopamine
      moieties of p-CO are L-phenylalanine and L-tyrosine, respectively. The treatment
      of potato tuber tissue with laminarin resulted in elevated activities of four
      enzymes which are putatively involved in p-CO biosynthesis: phenylalanine ammonia
      lyase (PAL; EC 4.3.1.5), 4-hydroxycinnamic acid:CoA ligase (4CL; EC 6.2.1.12),
      hydroxycinnamoyl-CoA:tyramine N-(hydroxycinnamoyl)transferase (THT; EC 2.3.1.110)
      and tyrosine decarboxylase (TyrDC; EC 4.1.1.25). Among these, the response of
      TyrDC was specific to laminarin treatment, thus indicating that the regulation of
      TyrDC activity is critical for the accumulation of p-CO in potato tuber tissue.

PMID- 10928549
TI  - Capacity of enzymes of the euphorbiacea Aleurites montana involved in CO2
      fixation, compared to plants having C3-, C4- and Crassulacean acid metabolism.
AB  - Capacities of phosphoenolpyruvate carboxylase (PEP-Co), ribulose bisphosphate
      carboxylase (Rubisco), NADP+ malic enzyme (ME) and of malate dehydrogenase (MDH)
      were measured in the Euphorbiacea Aleurites montana, grown under 700 ppm CO2 for
      four weeks prior to enzyme extraction. For comparison Bryophyllum daigremontiana
      (CAM). Saccharum officinarum (C4) and Capsicum frutescens (C3) were treated in
      the same way. PEP-Co capacity of Aleurites was in the range of 12-, that of
      Capsicum approx. 26 nmol x min(-1) x mg protein(-1), without significant
      influence of the light period or CO2-treatment. In contrast, the activity of the
      enzyme from Saccharum was, depending on the duration of light, 160- respectively
      96 times higher than that of the tung-oil tree. In Bryophyllum a rather low
      activity in the morning was increased during the day to approx. 230 nmol x min(
      1) x mg protein(-1) in plants grown in the greenhouse and to approx. 115 nmol x
      min(-1) x mg protein(-1) in those from the growth chamber. Malate was hardly
      detectable in extracts of Aleurites, whereas it was high in Bryophyllum,
      depending on the light period. The ratio of average PEP-Co to Rub-Co capacity was
      high for the CAM-plant (20:1), somewhat lower for sugar cane (10:1), but almost
      at equality for Aleurites (0.9:1) and chilli (0.8:1). For the NADP+ malic enzyme,
      low capacity (20 to 28 nmol x min(-1) x mg protein(-1)) was found for Aleurites
      and for Capsicum, whereas it was 10 to 17 times higher in Saccharum. In
      Bryophyllum, the activity was up to 80 nmol x min(-1) x mg protein, dependent on
      light period. MDH capacity was extremely high in all plants investigated. Highest
      rates (10-20 micromol x min(-1) x mg protein(-1)), were obtained for Bryophyllum,
      followed by sugar cane and Capsicum with 5-8 micromol x min(-1) x mg protein(-1).
      Again, the lowest capacity was found in extracts of Aleurites with approx. 1.3 to
      1.6 micromol x min(-1) x m protein(-1). Thus, in Aleurites montana no indication
      for C4- or Crassulacean acid metabolism was obtained. Therefore, the earlier
      observed very efficient uptake of CO2 cannot be explained by a high expression of
      the PEP-Co protein, known to occur in CAM- and C4-plants.

PMID- 10928550
TI  - Effects of naturally occurring polyols and urea on mitochondrial F0F1ATPase.
AB  - We show that urea inhibits the ATPase activity of MgATP submitochondrial
      particles (MgATP-SMP) with Ki = 0.7 M, probably as a result of direct interaction
      with the structure of F0F1-ATPase. Counteracting compounds (sorbitol, mannitol or
      inositol), despite slightly (10-20%) inhibiting the ATPase activity, also protect
      the F0F1-ATPase against denaturation by urea. However, this protection was only
      observed at low urea concentrations (less than 1.5 M), and in the presence of
      three polyols, the Ki for urea shift from 0.7 M to 1.2 M. Urea also increases the
      initial activation rate of latent MgATP-SMP in a dose-dependent-manner. However,
      when the particles (0.5 mg/ml) were preincubated in the presence of 1 M, 2 M or 3
      M urea, a decrease in the activation level occurred after 1 h, 30 and 10 min,
      respectively. At high MgATP-SMP concentration (3 mg/ml) a decrease in activation
      was observed after 2 h, 1 h and 20 min, respectively. These data indicate that
      the effect of urea on the activation of MgATP-SMP depends on time, urea and
      protein concentrations. It was also observed that polyols suppress the activation
      of latent MgATP-SMP in a dose-dependent manner, and protect the particles against
      urea denaturation during activation. We suppose that a decrease in membrane
      mobility promoted by interactions of polyols with phospholipids around the F0F1
      ATPase may also increase the compactation of protein structure, explaining the
      inhibition of natural inhibitor protein of ATPase (IF1) release and the
      activation of the enzyme.

PMID- 10928551
TI  - Synthetic taxonomy of Rosa races using ACT-STATIS.
AB  - Fifteen Rosa cultivated races were described by means of phenotypic frequencies
      (11 tables). Two groups of correlated contingency tables were identified by ACT
      STATIS (Analyse Conjointe de Tableaux-Structuration de Tableaux a Trois Indices
      de la Statistique) interstructure analysis. Three data sets appeared to be
      independent from the others. Typologies of races were obtained after ACT-STATIS
      compromise analyses for the two groups of correlated tables, and after Principal
      Component Analyses for the independent data sets. Each typology was original and
      variously influenced by genealogical structure, mutation or artificial selection
      pressures. A weighted synthesis was attempted in order to build a taxonomy of
      races taking into account these diversity factors. The good agreement between the
      resulting classification and the assumptions about the history of Rosa
      domestication advocated for a wider utilization of ACT-STATIS and RV coefficient
      when the relationships between individuals or populations have to be studied on
      the basis of their similarities.

PMID- 10928552
TI  - Instability of three-dimensional structures in ribosomal cores evidenced by
      microcalorimetric studies.
AB  - In this paper we show a microcalorimetric investigation carried out on the so
      called cores, i.e. ribosomes deprived of select proteins by LiCl treatment.
      Thermal degradation of native ribosomes gives rise to two thermal transitions
      occurring at different temperatures. In the cores the high temperature peak
      persists even after treatment at very high ion strength (2 M LiCl). This strongly
      suggests the existence of a very stable structure that was previously observed
      also in particles treated with agents that hydrolyze the RNA moiety. The low
      temperature peak gradually but dramatically decreases even though it never
      disappears completely. This indicates that the treatment to obtain ribosomal
      cores does not cause complete unfolding of the particle but only the
      destabilization of a structural three-dimensional domain present in native
      ribosomes. These data are discussed in the light of previous results obtained by
      dielectric spectroscopy and microcalorimetric studies on ribosomal particles.

PMID- 10928553
TI  - Hydration of alkylammonium salt micelles--influence of bromide and chloride
      counterions.
AB  - The micellization process of dodecyltrimethylammonium chloride (DTAC) and bromide
      (DTAB) was studied. Nuclear magnetic resonance method was used. The 1H NMR and
      13C NMR spectra were taken at higher and lower concentrations than the critical
      micelle concentrations (CMC) of the compounds studied. Chemical shifts were
      analysed. The studies performed were prompted by earlier calorimetric
      measurements which showed that there were significant qualitative and
      quantitative differences in the micellization process of the compounds studied.
      Namely, DTAB micelle dissociation was found to be an endothermic process while
      that of DTAC was exothermic. The differences found must be the result of
      differentiated influence of bromide and chloride counterions on the micellization
      process, including the phenomenon of micelle hydration. The objective of the work
      was to check whether cationic surfactant counterions can influence the micelle
      hydration process. Indeed, DTAB and DTAC, as monomers, exhibit similar
      hydrophobic hydration, but DTAB micelles are more hydrated than DTAC ones. It
      seems that the differences found in micellization of both salts studied may be
      attributed to different physicochemical properties of bromide and chloride ions,
      such as their mobilities and radii of their hydrated forms. Moreover, the effect
      of anions on the water structure must be taken into account. It is important
      whether the anions can be classified as water ordering kosmotropes, that hold the
      first hydration shell tightly, or water disordering chaotropes, that hold water
      molecules in that shell loosely.

PMID- 10928554
TI  - The effect of the lipid bilayer state on fluorescence intensity of fluorescein-PE
      in a saturated lipid bilayer.
AB  - Fluorescein-PE is a fluorescence probe that is used as a membrane label or a
      sensor of surface associated processes. Fluorescein-PE fluorescence intensity
      depends not only on bulk pH, but also on the local electrostatic potential, which
      affects the local membrane interface proton concentration. The pH sensitivity and
      hydrophilic character of the fluorescein moiety was used to detect conformational
      changes at the lipid bilayer surface. When located in the
      dipalmitoylphosphatidylcholine (DPPC) bilayer, probe fluorescence depends on
      conformational changes that occur during phase transitions. Relative fluorescence
      intensity changes more at pretransition than at the main phase transition
      temperature, indicating that interface conformation affects the condition in the
      vicinity of the membrane. Local electrostatic potential depends on surface charge
      density, the local dielectric constant, salt concentration and water
      organisation. Initial increase in fluorescence intensity at temperatures
      preceding that of pretransition can be explained by the decreased value of the
      dielectric constant in the lipid polar headgroups region related in turn to
      decreased water organisation within the membrane interface. The abrupt decrease
      in fluorescence intensity at temperatures between 25 degrees C and 35 degrees C
      (DPPC pretransition) is likely to be caused by an increased value of the
      electrostatic potential, induced by an elevated value of the dielectric constant
      within the phosphate group region. Further increase in the fluorescence intensity
      at temperatures above that of the gel-liquid phase transition correlates with the
      calculated decreased surface electrostatic potential. Above the main phase
      transition temperature, fluorescence intensity increase at a salt concentration
      of 140 mM is larger than with 14 mM. This results from a sharp decline of the
      electrostatic potential induced by the phosphocholine dipole as a function of
      distance from the membrane surface.

PMID- 10928555
TI  - New prostaglandins from the chemically defended soft coral Plexaura nina.
AB  - Three new prostaglandins were isolated as minor constituents of the organic
      extract from the Caribbean soft coral Plexaura nina. The structures of the new
      natural products were established by means of spectral data analysis, including
      2D NMR experiments. The unpalatability of the lipid extract of the coral and the
      defensive role of the major prostaglandin metabolites were determined by
      laboratory and field fish-feeding assays.

PMID- 10928556
TI  - Chemical variability of the volatile metabolites from the Caribbean corals of the
      genus Gorgonia.
AB  - The chemical composition of the investigated gorgonians showed a high level of
      individual variation and the colonies, according to their major contributors,
      were assigned to 10 distinct chemical profiles, among which A, C, E, and G were
      the most abundant ones. From the metabolites identified in the present study,
      either by means of GC/MS or using NMR techniques after conventional separation
      procedures, the novel cyclic ether 5,10-epoxymuurolane is found in significant
      quantities in D and I chemical profiles. Furanotriene, isofuranotriene and
      furanodiene could be referred as the most common metabolites of the genus, since
      they are found in 6 out of 10 chemical profiles. Isosericenine is, also, a
      significant contributor of H and I chemical profiles. A number of sesquiterpene
      hydrocarbons, such as curzerene, bicyclogermacrene, valencene, beta-bourbonene
      and beta-elemene, along with the oxygenated sesquiterpenes elemanolide and
      furoventalene, are present at varying concentrations in the majority of the
      chemical profiles. Metabolites of high discriminant value are: alpha-himachalene
      for the K chemical profile, alpha-santalene and its oxygenated derivatives for
      the G chemical profile and the three geometrical isomers of germacrone for the F
      chemical profile. Several chemical profiles showed narrow geographic
      distribution. Most of the chemical profiles are located in the north, while F
      inhabits mainly southern sites and the others are equally distributed. Finally,
      91% of the chemical profiles of the gorgonian colonies appeared to grow in all
      depths, while 9% did not inhabit deep-water environments. Most chemical profiles
      are less frequent at higher water depths with the exception of chemical profiles
      A and C.

PMID- 10928557
TI  - Suggested pharmacophagy of the African bushhopper Phymateus leprosus (Fabricius)
      (Pyrgomorphidae, Orthoptera).
AB  - The bushhopper Phymateus leprosus (Fabricius) in the field shows a special
      appetite for the milkweed Asclepias fruticosa. Asclepiadaceae, like Apocynaceae
      and Scrophulariaceae, contain cardiac glycosides. Raw and purified extracts of
      these plants phagostimulate larval and adult P. leprosus. We also screened
      natural and half-synthetic compounds found in those plant extracts. While
      saponins and sapogenins did not stimulate the animals, many cardiac glycosides
      and aglycones, offered on filter paper, proved to be phagostimulants.

PMID- 10928559
TI  - Seasonality of leptin levels in the BAT of the common shrew (Sorex araneus).
AB  - Leptin concentrations in the interscapular brown adipose tissue (IBAT) of the
      common shrew (Sorex araneus) were measured in different seasons. The leptin
      concentrations in IBAT were much higher than in the liver, where leptin is
      supposed to be of blood origin. In the heart muscle no detectable amount of
      leptin was found. There were clear seasonal variations in the leptin
      concentrations in IBAT. Leptin levels in IBAT were the lowest in November at the
      beginning of the winter. The concentrations increased, however, strongly after
      the onset of the permanent snow cover, and the highest concentrations were
      measured in December-January, when the weight of the animals was very low. In
      April-May, at the time when shrews attain sexual maturity, leptin concentrations
      in IBAT were lower than in the mid-winter, but significantly higher than in
      November. In overwintered adults the leptin concentrations were at the same level
      as in nonwintered subadults. Leptin originating from BAT may inform the central
      nervous system about the amount of nonshivering thermogenesis as well as the
      amount of feeding necessary for survival in the winter months.

PMID- 10928558
TI  - Expression of an HSP110 family, ischemia-responsive protein (irp94), in the rat
      brain after transient forebrain ischemia.
AB  - The transcriptional expression of an ischemia responsive protein (irp94) in the
      hippocampus of rats was analyzed by Northern blotting. A transient forebrain
      ischemia was induced in the rats by temporary occluding of the bilateral common
      carotid arteries (CCAs) for various periods, and then reperfusion. Among the
      frontal, parietal, temporal and occipital lobes, and the cerebellum and
      hippocampus, the maximum mRNA expression of irp94 was at the occipital lobe, and
      the minimum was at the parietal lobe following ten min of forebrain ischemia. The
      irp94 mRNA expression reached a maximum fifteen min after the transient ischemia.
      From twenty min on after the ischemia its expression decreased. After a ten-min
      ischemia and the following reperfusion, irp94 mRNA expression gradually increased
      in the first twelve h, and then decreased. The expression pattern was like that
      of the endoplasmic reticulum chaperone, Erp72, but not that of the cytosol
      chaperone, hsp72. In addition, when intracellular ATP was depleted with antimycin
      A the mRNA level of irp94 increased in a thyrocyte cell culture model. The
      results suggest that irp94, like a molecular chaperone, may play a role in
      protecting the cell against external stimulation, especially after a transient
      forebrain ischemia. Although future studies of irp94 will be required to clarify
      the interactions with other intracellular factors inducing ischemia or showing
      molecular chaperone activity, what is offered here is an insight into its
      functional role as a component of stress response in neurons that should be
      considered as a new therapeutic approach for the treatment of ischemia.

PMID- 10928560
TI  - The anticancer drug cisplatin interacts with the human erythrocyte membrane.
AB  - Drugs which exert their effects by interacting with DNA cause structural and
      functional membrane alterations which may be essential for growth inhibition by
      these agents. This paper describes the interaction of cisplatin with the human
      erythrocyte membrane and models constituted by bilayers of
      dimyristoylphosphatidylethanolamine (DMPE) and diacylphosphatidylserine (DAPS),
      representative of phospholipid classes located in the inner monolayer of the
      erythrocyte membrane, and of dimyristoylphosphatidylcholine (DMPC), a class
      present in its outer monolayer. Cisplatin ability to perturb DMPE, DAPS and DMPC
      bilayer structures was determined by X-ray diffraction and fluorescence
      spectroscopy. Electron microscopy disclosed that human erythrocytes incubated
      with 35 microM cisplatin, which is its therapeutical concentration in serum,
      developed cup-shaped forms (stomatocytes). According to the bilayer couple
      hypothesis, this means that the drug is inserted into the inner monolayer of the
      erythrocyte membrane, a conclusion supported by the studies on model systems.

PMID- 10928562
TI  - Localisation of a 3-hydroxy-3-methylglutaryl-coenzyme A reductase in the
      mitochondrial matrix of Trypanosoma brucei procyclics.
AB  - Contrary to Leishmania spp. and Trypanosoma cruzi, Trypanosoma brucei bloodstream
      forms do not synthesise their own sterols but take these compounds in the form of
      cholesterol directly from the mammalian host. However, procyclic insect stages
      synthesise ergosterol rather than cholesterol. Here the sub-cellular localisation
      of the first committed enzyme of this pathway of isoprenoid synthesis 3-hydroxy-3
      methylglutaryl-coenzyme A reductase in T. brucei procyclics (0.9 nmol x min(-1) x
      mg(-1) protein) was carried out using both cell-fractionation by isopycnic
      centrifugation and digitonin-titration experiments. The majority of the NADP+
      linked 3-hydroxy-3-methylglutaryl-coenzyme A reductase is a soluble enzyme
      present in the mitochondrial matrix with some additional membrane-associated
      activity in glycosomes and possibly in the endoplasmic reticulum. It is suggested
      that the active metabolism of threonine and/or leucine as preferred 2-carbon
      source for the incorporation of acetyl units into lipids and/or sterols in the
      mitochondrion of T. brucei procyclics is the explanation for a high 3-hydroxy-3
      methylglutaryl-coenzyme A reductase activity in these protozoan organelles.

PMID- 10928563
TI  - Phytochemical and pharmacognositc investigation of Bauhinia forficata Link
      (Leguminosae).
AB  - We have isolated two phytoconstituents present in the B. forficata leaves, a
      medicinal plant employed in folk medicine specially for the treatment of
      diabetes. These compounds were isolated by column chromatography and identified
      as beta-sitosterol and kaempferol-3,7-dirhamnoside (kaempferitrin) by
      spectroscopical data and comparison with authentic samples. A comparative study
      with different parts of the plant indicated that the latter is present only in
      the leaves, suggesting that it might be useful for a suitable quality control of
      phytotherapeutics which contain this organ of B. forficata in its composition.

PMID- 10928561
TI  - Antifungal effects of hydrolysable tannins and related compounds on
      dermatophytes, mould fungi and yeasts.
AB  - A series of hydrolysable tannins and related compounds was evaluated for
      antifungal activities against filamentous fungi (Epidermophyton floccosum;
      Microsporum canis; Microsporum gypseum; Trichophyton mentagrophytes; Trichophyton
      rubrum; Trichophyton tonsurans; Trichophyton terrestre; Penicillium italicum;
      Aspergillus fumigatus; Mucor racemosus; Rhizopus nigricans) and opportunistic
      yeasts (Candida albicans; Candida glabrata; Candidata krusei; Cryptococcus
      neoformans), using the agar dilution method. While all samples had no activity
      against the filamentous fungi in concentrations of 1.1-5.9 microM (1000
      microg/ml), the phenolic compounds displayed significant potencies against all
      the opportunistic yeasts tested but C. albicans, with minimum inhibitory
      concentrations ranging from 0.02 to 0.1 microM (16-125 microg/ml). Although the
      presence of galloyl groups in flavonoids did not necessarily produce activity,
      this structural element, an HHDP moiety or its oxidatively modified entity proved
      to be an important structural feature of hydrolysable tannins. Comparison of
      dilution methods provided strong evidence of dependence of MIC values on the test
      method. Employing the microdilution broth method, the ellagitannin corilagin (MIC
      0.8 nM) was found to be similarly potentially active as amphotericin B (MIC 0.5
      nM) and sertaconazole (MIC 0.9 nM) against Candida glabrata strains. The order of
      effectiveness observed being 64- and 4-8-fold increased for corilagin and the
      reference compounds respectively, when compared with that of the agar dilution
      test.

PMID- 10928564
TI  - Metabolites of 2-aminophenol from fruit bodies of Lepiota americana (Agaricales).
AB  - From the acetone extract of the North American toadstool Lepiota americana 2
      aminophenoxazin-3-one (1) and a novel amino-1,4-benzoquinone derivative,
      lepiotaquinone (2), were isolated. The structure of 2 was confirmed by its
      preparation from 2-aminophenol and amino-1,4-benzoquinone.

PMID- 10928565
TI  - The in vitro anti-fungal and anti-bacterial activities of beta-sitosterol from
      Senecio lyratus (Asteraceae).
AB  - From a methanol extract of dried-ground aerial parts of Senecio lyratus, an anti
      fungal and anti-bacterial active compound was isolated and identified as beta
      sitosterol by spectroscopic analysis.

PMID- 10928567
TI  - Motion analysis to the rescue?

PMID- 10928566
TI  - Prevalence of multi-drug resistant Salmonella typhi among clinically diagnosed
      typhoid fever patients in Lagos, Nigeria.
AB  - A total of 635 clinically diagnosed typhoid fever patients were bled from three
      different health institutions in the metropolis of Lagos, Nigeria over a period
      of 15 months, May 1997 to July 1998. Out of the total blood cultured, 101 (15.9%)
      isolates of Salmonella species were isolated of which 68 (67.3%) were S. typhi,
      17 (16.8%) and 16 (15.8%) were S. paratyphi A. and S. arizonae respectively. The
      overall isolation rate of S. typhi among patients is 10.7%, with most isolates
      45.9% found among the severely-ill young adults, age group 16-30 years. All
      isolates were subjected to anti-microbial susceptibility testing using 12
      different antibiotics: chloramphenicol, ampicillin, cotrimoxazole, gentamicin,
      colistin sulfate, nalidixic acid, nitrofurantoin, cefotaxime, tetracycline,
      streptomycin, ofloxacin and ciprofloxacin. All the S. typhi and S. paratyphi A
      isolates showed resistance to two or more of the 10 of 12 antibiotics tested
      particularly the 3-first-line antibiotics commonly used (chloramphenicol,
      ampicillin and cotrimoxazole) in the treatment of typhoid fever in Nigeria. No
      isolate showed resistance to ofloxacin and ciprofloxacin, however, nalidixic acid
      and gentamicin showed a moderate and appreciable inhibition to most of our
      isolates.

PMID- 10928568
TI  - Apraxia in diseases of the basal ganglia.

PMID- 10928569
TI  - Sleep episodes in Parkinson's disease: a wake-up call.

PMID- 10928570
TI  - The molecular biology of the autosomal-dominant cerebellar ataxias.
AB  - Autosomal-dominant cerebellar ataxias (ADCA) may present as progressive or
      paroxysmal disorders. While the progressive ataxias have been named
      spinocerebellar ataxias (SCA), the paroxysmal disorders are designated episodic
      ataxias (EA). Until now, three different mutational mechanisms resulting in
      distinctive pathogenesis have been identified. The first type of mutation present
      in SCA1, SCA2, SCA3, and SCA7 is an expanded CAG repeat in genes of unknown
      function that are translated into proteins with expanded polyglutamine tracts. A
      common ultrastructural feature of these disorders is the formation of neuronal
      intranuclear inclusions (NII) harboring the expanded disease proteins and a
      variety of other proteins. The pathogenic role of these inclusions has yet to be
      clarified. A second group of disorders is the result of mutations in genes that
      code for ion channels. In EA-1, a disorder characterized by episodes of ataxia
      provoked by movement and startle, missense mutations in a potassium channel gene,
      KCNA1, have been found. Patients with EA-2, another form of paroxysmal ataxia,
      carry nonsense mutations of the gene encoding the alpha1A voltage-dependent
      calcium channel subunit, CACNA1A, that are predicted to result in truncated
      channel proteins. In SCA6, a progressive ataxia, an expanded CAG repeat in the 3'
      translated region of the CACNA1A gene, has been found. The third type of mutation
      is an untranslated CTG expansion resembling the mutation found in myotonic
      dystrophy. It is associated with a progressive ataxia, SCA8.

PMID- 10928572
TI  - Disruption of spatial organization and interjoint coordination in Parkinson's
      disease, progressive supranuclear palsy, and multiple system atrophy.
AB  - Patients with basal ganglia diseases may exhibit ideomotor apraxia. To define the
      nature of the impairment of the action production system, we studied a repetitive
      gesture of slicing bread by three-dimensional computergraphic analysis in eight
      nondemented patients with Parkinson's disease in the "on" state, five with
      progressive supranuclear palsy and four with multiple system atrophy. Two
      patients with Parkinson's disease and two with progressive supranuclear palsy
      showed ideomotor apraxia for transitive movements on standard testing. A Selspott
      II system was used for kinematic analysis of wrist trajectories and angular
      motions of the shoulder and elbow joints. Patients with Parkinson's disease,
      progressive supranuclear palsy, and even some with multiple system atrophy
      exhibited kinematic deficits in the spatial precision of movement and velocity
      curvature relationships; in addition, they failed to maintain proper angle/angle
      relationships and to apportion their relative joint amplitudes normally. Spatial
      disruption of wrist trajectories was more severe in patients with ideomotor
      apraxia. We posit that the basal ganglia are part of the parallel parieto-frontal
      circuits devoted to sensorimotor integration for object-oriented behavior. The
      severity and characteristics of spatial abnormalities of a transitive movement
      would therefore depend on the location and distribution of the pathologic process
      within these circuits.

PMID- 10928571
TI  - Chronic effects of dopaminergic replacement on cognitive function in Parkinson's
      disease: a two-year follow-up study of previously untreated patients.
AB  - BACKGROUND: The cognitive effects of dopaminergic treatment in Parkinson's
      disease (PD) are still controversial. OBJECTIVE: To evaluate, in previously
      untreated patients with PD, whether chronic dopaminergic stimulation produces
      significant cognitive changes; whether they are sustained beyond the period of a
      few months; and whether the cognitive status of two motor-comparable groups is
      differently affected by levodopa and pergolide. DESIGN AND SUBJECTS: Parallel,
      randomized open study with blind neuropsychologic evaluation of 20 consecutive de
      novo patients with PD before and 3, 6, 12, 18, and 24 months after monotherapy
      with levodopa (n = 10) or pergolide (n = 10; 6-month monotherapy; pergolide +
      levodopa thereafter). RESULTS: Both treatments were associated with a significant
      improvement in motor scores and in tests assessing learning and long-term verbal
      and visual memory, visuospatial abilities, and various frontal tasks. While
      improvement in motor scores persisted, improvement in activities of daily living
      and in semantic fluency, Luria's rhythm and motor and long-term memory tests was
      not sustained at the 24-month examination. Further, performance on attentional,
      short-term memory, and the Stroop tests did not change over the course of the
      study. CONCLUSIONS: Both treatments were associated with incomplete but long
      lasting (18 mos) improvement in many cognitive tasks which declined thereafter,
      suggesting that dopaminergic replacement is not enough to compensate for all
      cognitive deficits of PD.

PMID- 10928573
TI  - The Bradykinesia Akinesia Incoordination Test (BRAIN TEST), an objective and user
      friendly means to evaluate patients with parkinsonism.
AB  - The BRAIN TEST, a computerized alternating finger tapping test, was performed on
      154 patients with parkinsonism to assess whether the test could be used as an
      objective tool to evaluate reliably the severity of Parkinson's disease (PD).
      Patients were instructed to tap two marked computer keyboard keys as fast and as
      accurately as possible for 60 seconds. The test generates the following
      variables: (1) kinesia score (KS)--number of keystrokes/min, (2) akinesia time
      (AT)--cumulative time that keys are depressed, (3) dysmetria score (DS)--a
      weighted score generated from incorrectly hit keys and corrected for speed, and
      (4) arrhythmia score (AS)--variance of the time interval between individual
      keystrokes. Among parkinsonian patients, we found a significant correlation
      between the four test parameters and PD rating scores of the Hoehn & Yahr, Schwab
      & England, and Unified PD Rating Scales (KS, AS, and AT p <0.001 and DS p <0.05).
      When compared with 73 parkinsonian patients 73 age- and sex-matched control
      subjects showed significantly higher KS and lower AT (p <0.001) as well as lower
      DS and AS (p = 0.05). The BRAIN TEST is a reliable and practical tool for
      evaluating the severity of parkinsonism and for distinguishing subjects with
      parkinsonism from normal control subjects. A version of the BRAIN TEST is
      available by FTP on the worldwide web
      (http://www.anaesthetist.com/software/brain.htm).

PMID- 10928574
TI  - Paroxysmal dystonic choreoathetosis: clinical features and investigation of
      pathophysiology in a large family.
AB  - Paroxysmal dystonic choreoathetosis (PDC) is an unusual hyperkinetic movement
      disorder characterized by attacks of chorea, dystonia, and ballism with onset in
      childhood. We report a large British family with dominantly inherited PDC linked
      to chromosome 2q and describe the clinical features in 20 affected family
      members. Attacks were precipitated by a variety of factors, including caffeine,
      alcohol, or emotion, and could be relieved by short periods of sleep in most
      subjects. The clinical features in the family are compared with those of 11 other
      PDC families in the literature and a core phenotype for PDC suggested. CSF
      monoamine metabolites measured at baseline and during an attack in one subject
      were found to increase during the attack. Magnetic resonance spectroscopy of
      brain and basal ganglia performed both during and between attacks was normal.
      Positron emission tomography using the D2 receptor ligand, 11C-raclopride, showed
      no abnormalities.

PMID- 10928575
TI  - Pramipexole-induced somnolence and episodes of daytime sleep.
AB  - Pramipexole is a non-ergot dopamine agonist used to treat Parkinson's disease
      (PD). Because of concern regarding driving safety, we evaluated the incidence and
      nature of somnolence experienced by patients receiving pramipexole in clinical
      trials at our center. A retrospective chart review was performed and structured
      interviews were conducted with patients who had reported moderate or severe
      somnolence. In addition, two patients underwent polysomnography (PSG) and
      multiple sleep latency tests (MSLT) while on and 2 weeks after discontinuation of
      pramipexole. Forty patients with PD participating in pramipexole clinical trials
      were identified. In the double-blind phases of the studies, 22 patients were
      randomized to pramipexole and 18 were randomized to placebo. Six patients
      assigned to pramipexole reported somnolence as an adverse event (1 moderate, 5
      mild) compared with two patients assigned to placebo (1 severe, 1 moderate; p =
      0.19, one-tailed Fisher's exact test). Thirty-seven patients participated in open
      label extension studies. Twenty-one (57%) reported somnolence as an adverse
      event. Eleven (30%) patients reported moderate somnolence and three (8%) patients
      reported severe somnolence. For patients with moderate or severe somnolence, the
      onset of worst-reported somnolence occurred at a mean (+/- standard error)
      pramipexole dose of 4.0 +/- 0.4 mg (range, 0.75-4.5 mg) per day. Patients had
      been taking pramipexole for a total of 10.0 +/- 1.5 months (range, .03-22 mos)
      and at their maximal dose for 6.7 +/- 1.5 months (range, .03-20 mos). During
      structured interviews with 12 of the 14 patients reporting moderate or severe
      somnolence, seven reported falling asleep while driving and two reported minor
      motor vehicle accidents caused by falling asleep. Most patients reported
      relatively continuous drowsiness that led to falling asleep without acute warning
      during periods of inactivity. Three patients reported discreet waves of
      irresistible sleepiness heralded by prodromal symptoms occurring against a
      background of normal wakefulness. MSLT in two of these patients revealed
      decreased latency to sleep without early onset of rapid eye movements. Sleep
      latency normalized after withdrawal of pramipexole. Intensive patient education
      is necessary to prevent motor vehicle accidents in patients taking pramipexole.
      We recommend that patients who are experiencing generalized drowsiness and
      falling asleep during periods of inactivity be instructed not to drive because
      these patients do fall asleep without acute warning. Somnolence usually resolves
      with pramipexole dose reduction or discontinuation. Patients should also be
      alerted to pull over and stop driving immediately if they feel a wave of
      sleepiness coming on. Patient education and compliance are critical to maximize
      safety.

PMID- 10928576
TI  - The use of dopamine agonists in very elderly patients with Parkinson's disease.
AB  - BACKGROUND: Controversy exists regarding the use of dopamine receptor agonists in
      elderly patients with Parkinson's disease because of concern about a high rate of
      intolerable side effects. METHODS: A retrospective chart review was used to
      examine our experience with dopamine agonist use in the very elderly by
      identifying patients in our Parkinson's disease database who were over the age of
      80 years and who had received agonists. Sixty-nine patients were identified who
      had 120 separate trials of agonist therapy. Successful treatment with the agonist
      was defined as maintenance of the agonist for a minimum of 6 months. RESULTS: The
      overall success rate among the very elderly for an agonist trial was 46%. Success
      rates for individual agonists were 15 of 27 (56%) bromocriptine, 18 of 34 (53%)
      pergolide, 17 of 43 (40%) pramipexole, and 5 of 16 (31%) ropinirole. In
      successful trials with bromocriptine, the mean daily dose was 12.8 mg, mean
      duration of treatment was 40 months, and mean age at drug initiation was 82
      years; for pergolide it was 1.8 mg, 32 months, and 83 years; for pramipexole 2.7
      mg, 14 months, and 83 years, and for ropinirole 10.6 mg, 11 months, and 83 years.
      CONCLUSION: This study demonstrated that therapeutic dosages of dopamine agonists
      were well tolerated by 46% of very elderly patients who received a trial of an
      agonist. These results indicate that dopamine receptor agonist therapeutic trials
      are warranted in selected very elderly patients.

PMID- 10928577
TI  - Anxiety disorders and depressive disorders preceding Parkinson's disease: a case
      control study.
AB  - We studied the association between preceding psychiatric disorders and
      Parkinson's disease (PD) using a case-control design. We used the medical records
      linkage system of the Rochester Epidemiology Project to identify 196 subjects who
      developed PD in Olmsted County, Minnesota, during the years 1976-1995. Each case
      was matched by age (+/-1 yr) and sex to a general population control. We reviewed
      the complete medical records of cases and control subjects to detect preceding
      psychiatric disorders. The frequency of psychiatric disorders was higher in cases
      than in control subjects; the odds ratio was 2.2 for anxiety disorders (95%
      confidence interval [95% CI] = 1.4-3.4; p = 0.0003), 1.9 for depressive disorders
      (95% CI = 1.1-3.2; p = 0.02), and 2.4 for both anxiety disorders and depressive
      disorders occurring in the same individual (95% CI = 1.2-4.8; p = 0.02). When we
      restricted analyses to disorders present 5 years or more before the onset of
      motor symptoms of PD, the association with depressive disorders lost statistical
      significance. However, the association with anxiety disorders remained
      significant for disorders present 5, 10, or 20 years before onset of motor
      symptoms. Our results suggest that anxiety disorders and depressive disorders are
      associated with PD and that the causative process or the risk factors underlying
      PD are present many years before the appearance of motor symptoms.

PMID- 10928578
TI  - Gabapentin for essential tremor: a multiple-dose, double-blind, placebo
      controlled trial.
AB  - Essential tremor (ET) is a common movement disorder that often becomes refractory
      to conventional pharmacologic management. Open-label studies suggest that
      gabapentin is efficacious for ET, but the results of controlled trials have been
      mixed. To determine the efficacy and tolerability of gabapentin in ET, we
      conducted a double-blind, placebo-controlled, cross-over trial evaluating two
      doses (1800 mg per day and 3600 mg per day; N = 25). Patients on other ET
      medications were maintained on their concurrent medications for 3 months prior to
      study initiation and throughout the study. Twenty patients (mean age, 69.9 +/-
      6.1 yrs) completed the study. Overall, patient global assessments (p <0.05),
      observed tremor scores (p <0.005), water pouring scores (p <0.05), and activities
      of daily living scores (p <0.005) significantly improved. Accelerometry scores,
      spirographs, and investigator global impression scores did not improve. The
      results were similar for high and low doses. Statistical regression models did
      not demonstrate any significant predictors for response. Gabapentin may be
      effective in some cases of ET.

PMID- 10928579
TI  - Inter- and intralimb oscillator coupling in parkinsonian tremor.
AB  - This study reports the findings of an analysis of temporal correlation between
      tremor of different muscles of the same and different limbs in four patients with
      Parkinson's disease. Spectral coherence methods were used for determining whether
      simultaneously occurring oscillations in the electromyograms of different muscles
      are statistically coupled. The incidence of significant coherence was
      considerably higher for muscle pairs in the same limb than for pairs in different
      limbs; Parkinson's disease tremor is coupled within but not between limbs.
      Because the characteristics of tremor are known to vary under different
      behavioral situations, the intralimb coupling was examined for different tasks. A
      mental arithmetic task resulted in an increase in the coherence between muscles
      of the same limb, whereas the finger-to-nose task decreased the coherence. No
      significant change in coherence was found for a postural task. The amplitude and
      regularity of tremor electromyography showed changes analogous to those in
      coherence. These results support the hypothesis that tremor in different limbs
      results from the activity of several neural circuits oscillating independently.
      The results also emphasize the value of these methods for rigorously
      characterizing tremor, in relation to disease state, behavioral conditions, and
      the selection of treatment strategies.

PMID- 10928580
TI  - Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT
      striatal uptake.
AB  - The variability in clinical features and the masking effects of drug therapy in
      Parkinson's disease (PD) can affect clinical assessment of disease severity. The
      aim of this study was to assess the imaging of dopamine transporters using 123I
      FP-CIT SPECT and its correlation with disease staging, severity, and duration.
      Differences between the clinical severity of the onset and non-onset side and the
      corresponding striatal uptake ratios were also examined. Forty-one patients with
      PD (nine unilateral, 32 bilateral clinical features) were studied. Clinical
      severity was determined by using the Unified Parkinson's Disease Rating Score
      (UPDRS). Unilateral UPDRS was calculated from unilateral arm and leg resting and
      action tremor, rigidity, finger taps, hand movements, alternating movements, and
      leg agility. 123I-FP-CIT striatal uptake was expressed as the ratio of
      specific:nonspecific (SP:NS) uptake for defined brain areas. Patients with PD who
      had unilateral symptoms showed a significant difference between the ipsilateral
      and contralateral SP:NS ratios in both the caudate and putamen, but there was a
      considerable overlap between between the two sides. This result was repeated in
      patients with bilateral symptoms and there was overlap of SP:NS ratios between
      the two groups. For the whole group of patients with PD, striatum, caudate, and
      putamen SP:NS ratios correlated with disease severity assessed by UPDRS and
      duration of disease. The SP:NS ratios correlated with the bradykinesia subscore
      but not with rigidity or tremor subscore. In conclusion, this study provides
      further evidence that the SP:NS ratio is a robust measure of disease severity
      correlating with duration of PD. However, variability in uptake values suggest
      that factors other than nigrostriatal degeneration may contribute to disease
      severity. Correlation with bradykinesia but not with tremor may indicate an
      origin for tremor outwith the dopamine transporter system. 123I-FP-CIT SPECT
      offers significant potential in defining the nigrostriatal changes in PD.

PMID- 10928581
TI  - Stridor and death in multiple system atrophy.
AB  - Patients with multiple system atrophy (MSA) have a mean survival of 8 to 10
      years. Nocturnal stridor has been considered a poor prognostic feature. We
      analyzed demographic, clinical, and polysomnographic data and obtained follow-up
      information from 42 patients with MSA (30 with follow-up data) seen in a Sleep
      Disorders Center. Group I consisted of 17 patients with nocturnal stridor,
      including seven with daytime stridor. Group II consisted of 25 patients without
      stridor. Analysis of survival curves of 30 patients with follow-up information
      showed a significantly shorter survival from the sleep evaluation, but not from
      disease onset, for patients with stridor compared with those without. Nine of 11
      patients with stridor died a median of 2 years from presentation and the only two
      survivors had undergone tracheostomy. Patients with daytime stridor and immobile
      vocal cords had especially poor prognoses. However, two of four patients with
      tracheostomies also died, as did six of 19 without stridor. We postulate that
      central hypoventilation and its complications may have been responsible for many
      of these other deaths. We conclude that stridor does carry a poor prognosis in
      patients with MSA but that there are also other causes of death. We recommend
      consideration of tracheostomy for patients with MSA who have stridor, but also
      assessment for central hypoventilation and appropriate management if it is
      present.

PMID- 10928582
TI  - Adult Chediak-Higashi parkinsonian syndrome with dystonia.
AB  - Chediak-Higashi syndrome (CHS) is a rare autosomal-recessive disorder
      characterized by immune deficiency, partial oculocutaneous albinism, and large
      eosinophilic, peroxidase-positive inclusion bodies in granule-containing cells.
      The adult form of CHS manifests during late childhood to early adulthood and is
      marked by various neurologic sequelae, including parkinsonism, dementia,
      spinocerebellar degeneration, and peripheral neuropathy. We report the case of a
      29-year-old man with adult CHS who exhibited a progressive asymmetric
      parkinsonism, including rest tremor, and axial, cervical, and appendicular
      dystonia. The diagnosis was confirmed by the presence of characteristic large
      peroxidase-positive granules within leukocytes and markedly decreased natural
      killer cell function. Levodopa/carbidopa and amantadine provided benefit for
      tremor. CHS, although rare, should be considered in the differential diagnosis of
      young adult parkinsonism.

PMID- 10928583
TI  - Focal shoulder-elevation dystonia.
AB  - We describe 13 cases of isolated focal dystonia of the shoulder with dystonic
      elevation but without clinically obvious cervical dystonia. All had significant
      trapezius muscle hypertrophy and limitation of shoulder movement causing
      substantial morbidity. In nine, this developed in the immediate aftermath of
      shoulder region trauma, most often a motor vehicle accident; clinically
      significant head trauma was not a factor. In two other cases this developed in
      the context of chronic heavy labor (suggesting possible overuse) and in one other
      it developed concurrent with the symptoms of discogenic cervical (C6-7)
      radiculopathy. In the one remaining case, no precipitating factors were
      identified. Preexisting risk factors for dystonia, such as dopamine antagonist
      drug use, family history of dystonia, or prior brain injury, were not identified
      in these patients. Administration of medications used to treat dystonia was
      unsuccessful but botulinum toxin therapy was beneficial in all six treated cases.

PMID- 10928584
TI  - Case-control study of debrisoquine 4-hydroxylase, N-acetyltransferase 2, and
      apolipoprotein E gene polymorphisms in Parkinson's disease.
AB  - We investigated the association of Parkinson's disease (PD) with two genes
      encoding liver-detoxifying enzymes, debrisoquine 4-hydroxylase (CYP2D6) and N
      acetyltransferase 2 (NAT2), and with one gene related to Alzheimer's disease,
      apolipoprotein E (APOE). In a sample of 139 unrelated PD cases and 113 control
      subjects, the NAT2 M3 allele was associated with PD (odds ratio = 7.9; 95%
      confidence interval = 1.7-36.3). Case-control analyses for CYP2D6, APOE, and NAT2
      M1 or M2 did not show a significant association. However, the age at onset of PD
      was significantly earlier in cases with the APOE epsilon2/epsilon3 genotype than
      in cases with the epsilon3/epsilon3 genotype.

PMID- 10928585
TI  - 19th-century American contributions to the recording of tremors.
AB  - Studies of tremor in the 19th century were based initially on simple observation
      and later on the use of crude graphic recording devices that had been modified
      from instruments developed for other purposes. Like several European
      contemporaries, American investigators studying tremor used and adapted various
      existing instruments, including tambours and sphygmographs. A tambour used a drum
      shaped pneumatic mechanism to transmit movements to a recording instrument,
      whereas the sphygmograph was a nonpneumatic mechanical device initially used to
      record the pulse. 19th-century American neurologists who used such devices
      included Frederick Peterson, Hobart Amory Hare, Charles Loomis Dana, and Augustus
      A. Eshner. Their measurements of tremor frequency were generally consistent with
      modern estimates for various types of tremor. Eshner, in particular, was
      frustrated by the overlap of frequency domains for tremors in different diseases,
      because this precluded use of tremor frequency alone as a differentiating feature
      for diagnosis. Peterson and Dana recognized the variation in tremor frequency in
      different body parts resulting from different natural resonance frequencies of
      these parts as a function of weight and elastic properties. Peterson, Dana, and
      Eshner also recognized that tremor amplitude and frequency are inversely related.
      Finally, these 19th-century investigators recognized that the tremor of
      Parkinson's disease is a relatively low-frequency rest tremor, suppressed by
      action, and generally synchronous in symmetric body parts, but varying in
      amplitude and frequency in different body parts or over time.

PMID- 10928586
TI  - Neurosyphilis presenting as progressive supranuclear palsy.

PMID- 10928587
TI  - Progressive myoclonic ataxia associated with celiac disease presenting as
      unilateral cortical tremor and dystonia.

PMID- 10928589
TI  - Myasthenia gravis after botulinum toxin A for Meige syndrome.

PMID- 10928588
TI  - Subhypnotic doses of zolpidem oppose dopaminergic-induced dyskinesia in
      Parkinson's disease.

PMID- 10928590
TI  - Test-retest reliability of patient information on age of onset in essential
      tremor.

PMID- 10928591
TI  - Chorea and jaw-opening dystonia as a manifestation of NeuroBehcet's syndrome.

PMID- 10928592
TI  - Young-onset Parkinson's disease: a clinical pathologic description of two
      siblings.

PMID- 10928593
TI  - Posterior fossa arachnoid cyst associated with an exertional tremor.

PMID- 10928594
TI  - Probable Cornelia de Lange syndrome with progressive parkinsonism and dystonia.

PMID- 10928595
TI  - Periodic limb movements in syringomyelia and syringobulbia.

PMID- 10928596
TI  - Bilateral subthalamic nucleus stimulation in a parkinsonian patient with previous
      unilateral pallidotomy and thalamotomy.

PMID- 10928597
TI  - High-frequency ventilation in neonates.
AB  - High-frequency ventilation (HFV) has been advocated to reduce lung injury and
      chronic lung disease (CLD) in preterm infants. Several randomized controlled
      trials have compared HFV with conventional mechanical ventilation (CMV) in
      preterm and term infants. This review first discusses animal data pertinent to
      optimizing the application of HFV in preterm infants. Second, a meta-analysis of
      all randomized controlled trials using HFV as an early intervention is presented.
      Finally, rescue use of HFV in preterm and term infants with respiratory failure
      or air leak syndromes is summarized. Eleven trials of early intervention with HFV
      are included in the meta analysis. Overall, chronic lung disease at 36 weeks
      postmenstrual age was reduced in patients treated with HFV, but mortality was not
      changed. The decrease in CLD, however, is confounded, as it is only based on
      small trials, whereas no pulmonary benefit was found in the three largest trials.
      Furthermore, HFV appears to increase the incidence of severe intracranial
      hemorrhages and periventricular leukomalacia. Therefore, routine elective use of
      HFV cannot be recommended at the present time. Limited data on rescue use of HFV
      suggest some benefits over continued CMV.

PMID- 10928598
TI  - Hypoglycemia: what is it for the neonate?
AB  - The definition of hypoglycemia in the newborn infant has remained controversial
      because of lack of significant correlation between plasma glucose concentration,
      clinical symptoms, and long-term sequelae. A threshold value for plasma glucose
      at which clinical intervention should be considered is important because of the
      potential for serious neurological injury. In this review, we have described
      threshold values for plasma glucose in the newborn infant, based upon available
      data, at which the clinician should consider close monitoring and therapeutic
      interventions aimed at increasing the glucose level. In clinically symptomatic
      infants, plasma glucose concentrations of 45 mg/dL (2.5 mmol/L) or less should be
      considered as threshold for intervention. In an asymptomatic baby and in those at
      risk for hypoglycemia, irrespective of gestational and postnatal age, plasma
      glucose values less than 36 mg/dL (2.0 mmol/L) should be considered as threshold
      levels. Variances from these criteria, as in breast-fed infants, are discussed.
      The threshold values described for surveillance and intervention should be
      separated from the targeted therapeutic values which should be in the range of 72
      90 mg/dL (4-5 mmol/L).

PMID- 10928599
TI  - Maternal risk factors for perinatal septicemia due to the Enterobacteriaceae.
AB  - Cases of perinatal septicemia due to the Enterobactericeae, which manifest in the
      first 24 hr of life were analyzed for the presence or absence of the maternal
      risk factors defined in the CDC group B streptococcus (GBS) risk-factor protocol.
      Microbiological data involving blood culture isolates were reviewed for the
      recovery of an Enterobacteriaceae from January 1975 through June 1995.
      Enterobacteriaceae perinatal septicemia was defined as the recovery an
      Enterobacteriaceae from one or more set of blood cultures in the first 24-36 hr
      of life in conjuncture with clinical evidence of neonatal stress in the first 24
      hr. A case would also be considered of perinatal origin for cultures obtained up
      to 36 hr provided that evidence of clinical disease was present in the first 24
      hr of life. Fifteen cases of perinatal septicemia due to the Enterobacteriaceae
      were analyzed. All but four shared one or more maternal risk factors. The
      maternal risk criteria established to avert early-onset GBS disease are commonly
      encountered in women destined to have newborns with perinatal septicemia due to
      the Enterobacteriaceae. Antibiotic selection for risk-driven protocols for GBS
      avoidance may need to be broadened to address the issue of coverage for
      penicillin-sensitive and penicillin-resistant Enterobacteriaceae.

PMID- 10928600
TI  - Three cases with different presentation of fentanyl-induced muscle rigidity--a
      rare problem in intensive care of neonates.
AB  - We report about two newborns with sudden onset of inability of mechanical
      ventilation due to transient chest wall rigidity after fentanyl i.v. bolus of 2
      and 4 microg/kg, respectively, resulting in severe hypoxemia and secondary
      bradycardia. A third case developed a rigidity of the tongue after fentanyl
      bolus, which created some unusual difficulties in bypassing the tongue for
      insertion an endotracheal tube. Because of common usage of this agent for
      analgesia we direct attention to the possibility of fentanyl-induced muscle
      rigidity. We underline the necessity of a slow bolus injection to prevent this
      dangerous adverse effect and we recommend the administration of naloxone and/or
      muscle relaxants as therapy in conjunction with mechanical ventilation.

PMID- 10928601
TI  - Experience with newborn intensive care deaths in a tertiary setting.
AB  - The purpose of this paper is to report the longitudinal experience with deaths in
      a United States' newborn intensive care unit. Retrospective analysis comparing
      infant deaths in two epochs: Epoch 1: 1985-1988 (n = 127) and Epoch 2: 1991-1994
      (n = 75). Data included demographic factors, age at death, episodes of
      cardiopulmonary resuscitation, do not resuscitate status, and whether withdrawal
      of support occurred. Infants in Epoch 2 were significantly younger at birth (28.7
      +/- 0.7 vs. 30.6 +/- 0.5 wks', p = 0.02) and death (31.5 +/- 0.9 vs. 34.0 +/- 0.7
      wks', p = 0.02) than those in Epoch 1. There was no difference in length of stay
      (19.5 +/- 5.1 vs. 24.4 +/- 4.2 days, Epoch 2 vs. Epoch 1). Infants were more
      likely to receive cardiopulmonary resuscitation in Epoch 2 than Epoch 1 (60 vs.
      41%, p = 0.008). However, more infants in Epoch 2 also had do not resuscitate
      status (80% vs. 59%, p = 0.002) or withdrawal of support (72% vs. 52%, p =
      0.005). The majority of newborn intensive care deaths currently occur with do not
      resuscitate status and/or withdrawal of support.

PMID- 10928602
TI  - Septicemia due to multiresistant Klebsiella pneumoniae in a neonatal unit: a case
      control study.
AB  - An unusually high incidence of septicemia due to multiresistant Klebsiella
      pneumoniae occurred in the Aristotle University Neonatology Department. Forty
      neonates suffered from 42 episodes of septicemia. Mortality was 43% ranging from
      32% in neonates with birth weight (BW) - 1,500 g to 55% with < 1,500 g. No
      differences were found between 17 neonates who died and 23 survivors. All
      isolates were resistant to aminoglycosides, third-generation cephalosporins, and
      aztreonam, but susceptible to imipenem and ciprofloxacin. The neonates with
      septicemia due to K. pneumoniae were matched 1:1 with neonates without septicemia
      (31 pairs) or with neonates with septicemia due to other organisms (8 pairs)
      according to BW and time of admission. Factors associated with septicemia were
      mechanical ventilation (p = 0.004) and ongoing parenteral nutrition (p = 0.027).
      In a multivariate model, nutrition exhibited no independent association after
      adjusting for ventilation. No differences were detected between the patients with
      Klebsiella septicemia and those with septicemia due to other organisms. Enhanced
      Infection Control measures and a temporary change of antibiotic policy reduced
      this serious complication. Three small outbreaks of multiresistant K. pneumoniae
      previously reported in neonates are reviewed.

PMID- 10928603
TI  - Preterm prediction study: is socioeconomic status a risk factor for bacterial
      vaginosis in Black or in White women?
AB  - Bacterial vaginosis (BV), an important risk factor for preterm birth, is a more
      common infection in Black compared with White pregnant women. Because Black women
      in the United States are more likely to have lower measures of socioeconomic
      status (SES), this study examined the hypothesis that BV is associated with low
      SES. The project evaluated data from the Preterm Prediction Study of 2,929 women
      prospectively followed during their pregnancies. The women, who were screened for
      BV at 24 and 28 weeks of gestation, underwent a structured interview to evaluate
      demographic factors, SES, home and work environment, drug or alcohol use, and
      prior medical history. Black women in the study had many measures of lower SES
      compared with the White women, and reported less use of tobacco, alcohol and
      drugs. In neither the Black nor White women was an association found between BV
      and measures of SES (with the sole exception of "absence of a home telephone").
      Most measures of SES do not explain the difference in rates of BV in Black and in
      White pregnant women.

PMID- 10928604
TI  - Maturation of thermal capabilities in preterm infants.
AB  - Very low-birth-weight infants (VLBW) may initially require environmental
      temperatures higher than skin temperature. We examined the correlation between
      gestational age, birth weight, and the time to reach skin-air temperature
      equilibration (TTE) in VLBW infants. We also examined the effect of antenatal
      steroids on TTE in infants with birth weight < 1000 g. There is a significant
      exponential correlation between TTE and birth weight or gestational age (p <
      0.05). There was no significant change in TTE in infants who were treated
      antenatally with steroids, as compared with infants who were not treated.
      Multiple regression analysis with TTE as the dependent variable and birth weight
      or gestational age, race, betamethasone treatment, and gender as the independent
      variables showed a significant correlation between gestational age and TTE (p =
      0.04). We conclude that thermal capabilities are exponentially correlated with
      gestational age or birth weight.

PMID- 10928605
TI  - Esophageal achalasia in pregnancy.
AB  - Achalasia is rare motor disorder of esophageal smooth muscle. It has been linked
      to malnutrition during pregnancy leading to maternal and fetal mortality. We
      report a case of achalasia with intrauterine fetal death who succeeded in
      following pregnancy with good fetal and maternal outcome after operative
      treatment. A 34-year-old pregnant woman had intrauterine fetal death at 27
      gestational weeks due to severe and persistent maternal malnutrition during
      pregnancy. Achalasia was diagnosed postpartum and myotomy-fundoplasty was
      performed. She succeeded in normal delivery with a healthy baby 21 months after
      the operation. This case suggests the effect of severe achalasia of early onset
      on poor fetal outcome, and the efficacy of surgical myotomy for the improvement
      of following pregnant outcome.

PMID- 10928606
TI  - Chest radiography with a large-area detector based on cesium-iodide/amorphous
      silicon technology: image quality and dose requirement in comparison with an
      asymmetric screen-film system.
AB  - The purpose of this study was to evaluate a large-area, flat-panel X-ray
      detector, which uses cesium-iodide (CsI) and amorphous silicon (a-Si).
      Conventional images were compared with digital images acquired with equal dose
      (2.5 microGy) and with 50% dose reduction. Fifteen consecutive patients were
      studied prospectively using an asymmetric screen-film system (detector dose, 2.5
      microGy). Digital images were taken from the same patients in a posteroanterior
      view with detector doses of 2.5 and 1.25 microGy, respectively. The CsI/a-Si
      active-matrix imager had a panel-size of 43 x 43 cm, a matrix of 3 x 3k, and a
      pixel-pitch of 143 microm. Hard copies were presented in a random order to eight
      independent observers, who rated image quality according to six subjective
      quality criteria. Statistical significance of differences was evaluated with
      Student's t test for paired samples (confidence level, 95%). Digital radiographs
      with 2.5 and 1.25 microGy were superior to conventional images regarding all
      quality criteria. Statistically significant differences were observed for five of
      six criteria at a detector dose of 2.5 microGy and for only one quality feature
      at 1.25 microGy. Flat-panel digital imagers based on CsI/a-Si technique have the
      potential to replace conventional systems and might allow a reduction of
      radiation dose by 50% without loss of image quality.

PMID- 10928607
TI  - Lymphocytic interstitial pneumonia: follow-up CT findings in 14 patients.
AB  - The aim of the present study was to assess the evolution of various computed
      tomographic (CT) findings of lymphocytic interstitial pneumonia (LIP) with
      determination of potentially reversible or irreversible features. The study
      included 14 patients with biopsy-proved LIP who had serial thin-section CT
      examination 4 to 82 months (median 13 months) apart. Initial and follow-up CT
      scans were evaluated independently and then directly compared with each other by
      two observers. The main parenchymal abnormalities on the initial CT scan
      consisted of ground-glass attenuation (n = 14), thickening of interlobular septa
      (n = 13), centrilobular nodules (n = 12), cystic airspaces (n = 10), and airspace
      consolidation (n = 4). On follow-up CT, nine patients improved, one showed no
      change, and four showed increased extent of disease. With the exception of cysts,
      the parenchymal opacities were reversible. On follow-up CT, new cysts were seen
      in three patients; these developed mainly in areas with centrilobular nodules on
      initial CT. Honeycombing was seen on follow-up CT in four patients; in three
      patients it developed in areas of airspace consolidation and in one patient it
      developed in an area with ground-glass attenuation on initial CT. The majority of
      patients with LIP improved on follow-up. However, airspace consolidation may
      progress to honeycombing and centrilobular nodules may precede cystic formation.

PMID- 10928608
TI  - Low-dose, dynamic, expiratory thin-section CT of the lungs using a spiral CT
      scanner.
AB  - Seventeen patients with lung transplants were evaluated with inspiratory,
      postexpiratory, and low-dose, dynamic expiratory thin-section computed tomography
      (CT). Region of interest measurements were performed on inspiration and
      expiration images with both techniques, and mean lung attenuation changes between
      inspiration and expiration images were calculated and compared. Dynamic
      expiratory thin-section CT resulted in a significantly greater increase in lung
      attenuation than postexpiratory thin-section CT. Dynamic expiratory thin-section
      CT may prove useful in the evaluation of patients with lung diseases
      characterized by air flow obstruction with little increase in patient radiation
      dose.

PMID- 10928609
TI  - Pulmonary nodules and masses after lung and heart-lung transplantation.
AB  - The authors assess clinical and radiographic findings of pulmonary nodules and
      masses after lung and heart-lung transplantation. One hundred and fifty nine
      patients who survived at least 3 months after lung and heart-lung transplantation
      were followed by serial chest radiographs for a median of 27 months. Single or
      multiple lung nodules or masses were noted at chest radiography in 15 (9.4%) of
      159 patients. Imaging findings and causes of these nodules and masses were
      reviewed retrospectively. Infection was found in 10 (6%) of 159 patients.
      Specific pathogens (11 pathogens in 10 patients) were Aspergillus (n = 4),
      Mycobacteria (n = 4), and other bacteria (n = 3). Noninfectious causes were found
      in 5 (3%) of patients and included B-cell lymphoma (n = 2), bronchogenic
      carcinoma (n = 2), and pulmonary infarcts (n = 1). Nodules and masses appeared a
      median of 11 months after transplantation (range: 0.2 to 36 months). Five
      patients (33%) had single lesions; the other 10 (67%) patients had multiple
      lesions (range 2 to 50). Aspergillus lesions were most commonly located in the
      upper lobes, were cavitary in three of four patients, and all were fatal. Nodules
      and masses arose in the transplanted lung in 12 (80%) of the patients, and in the
      native lung in 3 (20%) of the patients (2 bronchogenic carcinoma, 1 M.
      tuberculosis simulating bronchogenic carcinoma). Nodules and masses detected by
      chest radiography are not uncommon (9.4%) after lung and heart-lung
      transplantation. Infections are more common than noninfectious causes of
      posttransplant nodules and masses. Specific clinical and imaging characteristics
      may provide clues to etiology.

PMID- 10928610
TI  - Bronchioloalveolar cell carcinoma: impact of histology on dominant CT pattern.
AB  - The authors set out to determine how histologic variability in bronchioloalveolar
      cell carcinoma impacts dominant radiographic patterns shown by computed
      tomography (CT). Thoracic CT's of all patients with pathologically confirmed
      bronchioloalveolar cell carcinoma diagnosed over a 36-month period were reviewed
      without knowledge of underlying histologic type. The dominant CT pattern was
      recorded as 1) air space consolidation; 2) focal nodule or mass; and 3)
      multicentric nodules or masses. Nodules and masses were further characterized
      according to borders, distribution, and associated findings, including
      spiculations and air bronchograms. Histology was independently reviewed. Twenty
      seven patients, 16 women and 11 men, mean age 60 years, were diagnosed with
      bronchioloalveolar cell carcinoma. In 6 (22%) of the 27 cases, the histology was
      mucinous, with malignant goblet cells identified. Five (83%) of the six mucinous
      neoplasms manifested as air space consolidation and three (50%) of the six
      presented with multiple nodules, in which two had coexisting air space
      consolidation. Of the remaining 21 cases (78%) with nonmucinous histology, the
      primary malignant cells of origin included Clara cells (n = 8), tall columnar
      epithelial cells (n = 7) and alveolar type II pneumocytes (n = 6). Sclerosis was
      a dominant histologic feature in 14 (67%) of the 21 cases. Seventeen (81%) of the
      nonmucinous neoplasms presented as isolated nodules or masses and four (19%)
      presented as multiple nodules or masses. Of these four patients with multifocal
      disease and nonmucinous histology, multiple bronchioloalveolar adenomas accounted
      for multicentricity in two of the patients. Significant correlations included air
      space consolidation with mucinous histology (p = 0.001) and focal nodule or mass
      with nonmucinous histology (p = 0.001). At CT of bronchioloalveolar cell
      carcinoma, the patterns of air-space consolidation correlate with mucinous
      histology and isolated nodules or masses with nonmucinous histology. The pattern
      of multiple nodules or masses, however, did not correlate with histology.
      Coexisting bronchioloalveolar adenomas can contribute to apparent multicentric
      disease in patients with nonmucinous histology.

PMID- 10928611
TI  - Unilateral absence of the left pulmonary artery associated with coronary-to
      bronchial artery anastomosis.
AB  - Unilateral absence of the pulmonary artery and bronchial-to-coronary artery
      anastomosis are rarely described congenital vascular anomalies. The authors
      report a case of a 49-year-old female presenting with both anomalies. The
      presenting symptoms and pertinent diagnostic imaging are described, including
      conventional radiographs, angiography, computed tomography, and magnetic
      resonance imaging, and the therapeutic options available are discussed.

PMID- 10928613
TI  - Literature retrieval on the world wide web.

PMID- 10928612
TI  - Paradoxical motion of the hemidiaphragm in patients with emphysema.
AB  - The authors evaluate paradoxical diaphragmatic motion using magnetic resonance
      (MR) imaging in patients with emphysema. The subjects were 12 healthy volunteers
      and 10 male patients with moderate to severe air flow obstruction. With subjects
      in the supine position, 30 sequential sagittal images of the bilateral lungs were
      obtained during quiet and forced breathing using a 1.5T MR unit with a body coil.
      The sequence was single shot fast spin echo (SSFSE) with half Fourier
      transformation. Subtraction images were made from the original images (by
      subtracting a given image from the preceding image), which visualized the chest
      wall motion as white or black bands on the edge of the lung fields. The authors
      evaluated both the original and subtraction images. MR imaging showed abnormal
      hemidiaphragmatic motion during forced breathing: the ventral portion of the
      hemidiaphragm moved downward while the dorsal part moved upward like a seesaw in
      6 patients. MR images also revealed abnormal ribcage motion; the ventral ribcage
      moved anteriorly when the hemidiaphragm moved upward in 7 patients. No abnormal
      motion was observed in healthy volunteers. MR is a noninvasive and useful tool
      for evaluating the asynchronous respiratory motion in patients with emphysema.

PMID- 10928614
TI  - Solitary pulmonary nodule due to dirofilariasis.
AB  - Pulmonary dirofilariasis can produce a noncalcified solitary nodule and therefore
      be mistaken for a lung cancer. Careful analysis of the imaging findings in this
      disease can suggest the proper evaluation and management in affected patients.

PMID- 10928615
TI  - Incidental detection of thoracic sarcoidosis on whole-body 18fluorine-2- fluoro-2
      deoxy-D-glucose positron emission tomography.
AB  - 18 Fluorine-2- Fluoro-2-Deoxy-D-Glucose positron emission tomography (18FDG PET)
      allows imaging of sites with increased metabolic activity. Increased metabolic
      activity in mediastinal nodes in sarcoidosis has been described. We report the
      prospective diagnosis of thoracic sarcoidosis on 18FDG PET based on extensive,
      peripheral, upper lobe parenchymal, and mediastinal nodal tracer uptake.

PMID- 10928616
TI  - Solitary aneurysm of the innominate vein.
AB  - Two cases of isolated saccular aneurysms of the innominate vein are presented
      that appeared as mediastinal masses. Contrast-enhanced computed tomography (CT)
      allowed for accurate diagnosis in one patient, while the second patient had
      atypical CT findings that led to thoracotomy for proper diagnosis. A diagnosis of
      innominate vein aneurysm should be considered when a uniform attenuation
      mediastinal mass is seen on CT so that unnecessary biopsy and surgery can be
      avoided.

PMID- 10928617
TI  - Systemic to pulmonary venous shunt in superior vena cava occlusion.
AB  - This report describes systemic-to-pulmonary venous connections at the pleural
      level resulting from superior vena cava occlusion. The interval development of
      new venous collaterals within a 3-year period represents an advanced
      manifestation of SVC occlusion in this patient with a history of pleural disease.
      In this case, progressive venous thrombosis caused by underlying
      hypercoaguability led to the development of collaterals in unusual sites,
      including systemic-to-pulmonary venous shunting, and resulting in progressive
      cyanosis and death.

PMID- 10928618
TI  - Risk factors for wheeze in the last 12 months in preschool children.
AB  - Most children with asthma develop their symptoms before the age of 5 years and
      many preschool wheezers continue to wheeze in the early school years. It is thus
      important to investigate the factors that predispose young children to wheeze.
      The objective of this study was to investigate the relevant environmental and
      family influences on recent wheeze (wheeze within the last 12 months) in
      preschool children. A cross-sectional study was conducted in five primary health
      clinics in the district of Kota Bharu from April to October 1998. Nurses from
      these clinics distributed Bahasa Malaysia questionnaires containing questions on
      asthma symptoms, environmental risk factors, family's social status and family
      history of atopy and wheeze to preschool children aged 1-5 years during their
      home visits. The respondents were parent(s) or carer(s) of the children. A total
      of 2,524 (87.7%) complete questionnaires were available for analysis of risk
      factors. One hundred and fifty six (6.2%) children had current wheeze.
      Significant risk factors associated with current wheeze were a family history of
      asthma (O.R. = 6.36, 95% C.I. = 4.45-9.09), neonatal hospital admission (O.R. =
      2.38, 95% C.I. = 1.51 - 3.75), and a maternal (O.R. = 2.12, 95% C.I. = 1.31-3.41)
      or paternal (O.R. = 1.52, 95% C.I. = 0.95-2.43) history of allergic rhinitis.
      Among environmental factors examined, namely, household pets, carpeting in
      bedroom, use of fumigation mats, mosquito coils and aerosol insect repellents,
      maternal and paternal smoking, and air conditioning, none were associated with an
      increased risk of wheeze. In conclusion, the strongest association with current
      wheeze was a family history of asthma. Also significant were neonatal hospital
      admission and a history of allergic rhinitis in either the mother or father. None
      of the environmental factors studied were related to current wheeze in preschool
      children.

PMID- 10928619
TI  - Renin angiotensin aldosterone system and drug allergies complicated with
      hypotension.
AB  - It has been discussed in several studies that non-immunologic factors, such as
      renin angiotensin aldosterone system (RAAS) may play a role in the
      pathophysiology of anaphylaxis. This study aimed to determine whether RAAS plays
      a part in the fall in blood pressure during drug reactions or not. Twenty
      patients who experienced hypotension during drug reaction and 15 healthy
      volunteers were enrolled in this study. None of the patients in the study or
      control groups were under treatment with any drug that was capable of influencing
      to RAAS. Serum levels of angiotensin-I (A-I), angiotensin-II (A-II), angiotensin
      converting enzyme (ACE) and aldosterone were measured in both study and control
      groups. The Mann-Whitney U test was used to compare the results of the groups.
      There were no statistically significant differences between the groups with
      respect to A-I, A-II, ACE and aldosterone levels. It was concluded that a fall in
      blood pressure during drug reaction must be the result of mast cell mediator
      effects on the vascular wall rather than RAAS impairment.

PMID- 10928620
TI  - Purification of human hemopoietic stem cells for transplantation in Thailand.
AB  - Stem cell transplantation (SCT) has become the therapy of choice for many
      hematologic and immunologic disorders. At present, only 25% of patients have
      suitable HLA-identical donors. In an attempt to increase the donor pool for SCT
      in Thailand and Southeast Asia, we developed a program whereby parents and
      mismatched siblings can be used as donors. In this preliminary study, after
      granulocyte-colony-stimulating factor (G-CSF) was given to adult donors,
      peripheral blood stem cells (PBSC) were collected and CD34+ cells purified using
      a CliniMACS immunomagnetic device (Miltenyi Biotec, Germany). In seven
      experiments, purified CD34+ cells could be obtained from G-CSF-stimulated PBSC in
      large numbers (1.71 +/- 0.19 x 10(8)), with high purity (93 +/- 2.4%) and
      excellent recovery (64.28% - 85.62%). Immune reactive T and NK cells were
      adequately depleted to less than 0.2%. The purification procedure can be
      completed within 3 hours. In conclusion, a clinical stem cell purification
      program using this novel device is now established in Thailand and for the first
      time in Southeast Asia. This should allow further development of advanced SCT
      therapy including haploidentical and mismatched CD34+ SCT for patients' lacking
      HLA-identical donors in this region.

PMID- 10928621
TI  - The first report of CCR5 delta 32 mutant in Thai injecting drug users.
AB  - CCR5, a chemokine receptor, is the principal coreceptor for macrophage-tropic HIV
      1 which is the most important variant for viral transmission. It has been
      demonstrated that a homozygous genotype of a 32-bp deletion in CCR5 gene
      (delta32CCR5) shows a high degree of resistance to HIV-1 infection. To
      demonstrate that delta32CCR5 does exist in Thai natives, the CCR5 genotypes and
      allelic frequencies in 860 Thai injecting drug users (IDUs) were determined by
      PCR and DNA sequencing. Of these, six (0.7%) were CCR5/delta32CCR5 heterozygotes
      and no homozygote was found. The overall delta32CCR5 allelic frequency was 0.0035
      and in HIV-1 seronegative (n = 490) and seropositive (n = 370) IDUs were 0.0051
      and 0.0004, respectively, which were not significantly different (p = 0.3776).
      Here we report that the delta32CCR5 does exist in Thai IDUs as it is present in
      other human races. Such low allelic frequency may indicate that this mutation
      does not attribute a significant role in HIV-1 transmission in Thai IDUs.

PMID- 10928622
TI  - Viral hepatitis: recent experiences from serological studies in Bangladesh.
AB  - Infections due to hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV) and
      hepatitis E (HEV) viruses are the major causes of hepatitis and are associated
      with significant morbidity and mortality in developing countries like Bangladesh.
      The present study was carried out to determine the prevalence of HBsAg, anti-HCV
      antibody, anti-HAV antibody and anti-HEV antibody in patients suspected of having
      infection by HBV, HCV, HAV and HEV, respectively. Antibody to HAV was detected in
      39% of subjects investigated. HBsAg was identified in 19% of subjects. Antibody
      to HCV and HEV was detected in 13% and 53% subjects, respectively. Infection with
      HAV was very high among children < or = 6 years of age (100%). On the contrary,
      exposure to HEV was higher in adult persons > or => 30 years of age (52%)
      compared to that in children < or = 6 years of age who had 0% incidence. Our
      study clearly indicates a high prevalence of those viruses, particularly of
      enterically transmitted HAV and HEV in Bangladesh, which appeared to be a serious
      health problem in this developing country. Control measures should be taken on an
      urgent basis to prevent the spread of infections by these viruses.

PMID- 10928623
TI  - Detection of factor V Leiden in Thai patients with venous thrombosis.
AB  - The molecular defect underlying activated protein C resistance (APC-R) is caused
      by a G to A point mutation in the codon for arginine 506 in the factor V gene
      (factor V Leiden) which is a major risk factor for venous thrombosis, especially
      in Caucasian populations. This study is an analysis of the Thai population to
      determine the prevalence of the factor V Leiden mutation. Twenty-seven patients
      with apparent venous thrombosis were divided into two groups according to APC-R
      test. Thirteen patients were diagnosed as positive for n-APC-SR, ratio < 0.8 and
      fourteen patients were diagnosed as negative for n-APC-SR, ratio > 0.8. Two of
      thirteen APC-R positive patients and one of fourteen APC-R negative patients were
      found to have the heterozygous allele for the factor V Leiden mutation but the
      homozygous allele was not detected in these groups of patients. Neither the
      heterozygous nor homozygous Leiden mutation was detected in 200 healthy volunteer
      blood donors. In conclusion, our findings indicate that factor V Leiden mutation
      is related to venous thrombosis in Thai people. Moreover, a further study of
      other mutations at the activated protein C cleavage sites of factor V and factor
      VIII is recommended.

PMID- 10928624
TI  - Serum interleukin-6 and interferon-gamma levels in patients with hepatitis B
      associated chronic liver disease.
AB  - Hepatitis B virus (HBV) infection can elicit a variety of clinical sequelae
      ranging from acute self-limited hepatitis to hepatocellular carcinoma, which are
      not attributable to a direct cytopathic effect of the virus but rather to the
      individual host's immune response. Cytokines, low-molecular-weight proteins with
      a broad range of activity, have been shown to be involved in the regulation of
      hepatocyte functions, as well as in the pathogenesis leading to liver damage. In
      the present study, we investigated the correlation between serum interleukin 6
      (IL-6) and interferon gamma (IFN-gamma) in altogether 75 patients chronically
      infected with HBV. They comprised 15 asymptomatic carriers, 15 chronic persistent
      hepatitis (CPH) and 15 chronic active hepatitis (CAH) patients, 15 cases of
      cirrhosis and 15 patients with hepatocellular carcinoma (HCC) previously
      diagnosed by serology and histology, respectively. IL-6 and IFN-gamma levels in
      their sera were determined using a commercially available kit. Our results showed
      various concentrations of serum IL-6 detectable in 6.7% of asymptomatic carriers,
      13.3% of patients with CPH, 20% of patients with CAH, 33.3% in cirrhotic patients
      and 66.7% in HCC. In contrast, serum IFN-gamma was only found in 13.3% of
      asymptomatic carriers and CAH, but could not be detected in the other groups. Our
      data demonstrated a positive correlation between serum IL-6 and clinical severity
      of chronic HBV infection, whereas the IFN-gamma levels appeared not to be
      correlated. From this we conclude that among chronic hepatitis patients IFN-gamma
      is mostly not expressed at a level detectable by serology, whereas according to
      other authors it is involved in the immediate immune response triggered by acute
      hepatitis. IL-6 on the other hand, might rather be responsible for liver
      inflammation and regeneration in chronic liver disease.

PMID- 10928625
TI  - Comparison of the RPHA and EIA techniques for the detection of HBs antigen among
      pregnant Thai women.
AB  - Five hundred serum samples obtained from pregnant women attending an antenatal
      clinic in Bangkok were tested for HBsAg by reverse passive hemagglutination assay
      (RPHA) and enzyme immunoassay (EIA). It was found that 21 (4.2%) and 28 (5.6%) of
      the sera were positive by RPHA and EIA, respectively. The sensitivity and
      specificity of the RPHA were 75% and 100%, respectively, when using EIA as the
      standard method. The RPHA positive predictive value was 100% and the negative
      predictive value was 98.5%. Accuracy was 98.6%. This study showed that the RPHA
      was simple and required inexpensive equipment, making it suitable for mass
      screening. However, the possibility of false negative readings due to low levels
      of HBsAg should be kept in mind, especially in the blood transfusion practice.

PMID- 10928626
TI  - The surface structure of catalysts activated with hydrogen donors as elucidated
      by multinuclear solid-state NMR.
AB  - 1H, 27Al and 31P MAS, and 13C and 29Si CP/MAS NMR spectroscopies, were used to
      characterize catalysts of Pd supported on various solids including SiO2, AlPO4
      and Mg3(PO4)2 that were activated with the chiral hydrogen-donor limonene. The
      above-mentioned techniques were used to check for the formation of an
      organopalladium complex between Pd2+ atoms and the olefin bonds in the limonene
      molecule on the catalyst surface. The results are compared with those obtained
      for catalysts activated in a hydrogen stream.

PMID- 10928628
TI  - Unusual proton Zeeman spin relaxation in an organic solid: several crystal
      polymorphs or different glass structures?
AB  - Solid state proton Zeeman relaxation rate R1z measurements in two isomers of an
      organic solid (1- and 2-ethylnaphthalene) are reported. The samples are liquids
      at room temperature and the temperature T and Larmor frequency omega dependence
      of R1z depends strongly on how the sample is solidified. Methyl group (CH3)
      rotation is responsible for the proton spin relaxation and the methyl groups
      serve as probes of the local environment. The R1z measurements clearly
      distinguish between different solid states due to the differences in local
      structure at the several-molecule level. The experiments cannot be used to
      determine the states of these Van der Waals solids although interpreting the
      relaxation rate data suggests the states are unusual. We propose that these
      systems might exist in two (2-ethylnaphthalene) or more (1-ethylnaphthalene)
      polycrystalline polymorphs or that we are observing distinguishable glassy
      states, or, both. A phase transition is observed in 1-ethylnaphthalene. Variable
      temperature X-ray studies of organic systems that solidify well below room
      temperature are difficult, or at least not routine, and proton spin relaxation
      measurements serve as a convenient starting point for investigating such systems.

PMID- 10928627
TI  - High-resolution solid state 13C nuclear magnetic resonance spectra of 3,4
      methylenedioxyamphetamine hydrochloride and related compounds and their mixtures
      with lactose.
AB  - Differences between solution and solid state 13C nuclear magnetic resonance
      spectra of some amphetamines namely, 3,4-methylenedioxyamphetamine HCI, (R.S)-MDA
      HCI, the methyl derivative 3,4-methylenedioxy-N-methylamphetamine x HCI, (R,S)
      MDMA x HCI, the ethyl derivative, (R,S)-MDEA x HCI, and the analogues (R,S)
      methamphetamine HCI, (-)-ephedrine x HCI (the 3R,2S enantiomer as numbered here),
      and (+)-pseudo-ephedrine x HCI (the 3S,2S enantiomer as numbered here) have been
      studied and related to their crystal structure. For (R,S)-MDMA x HCI, an
      interesting new finding is that the observed solid state chemical shifts changed
      when lactose monohydrate was added as a dry powder and thoroughly mixed at room
      temperature. This experiment mimicked the illicit production of "Ecstasy"
      tablets. The mixing phenomena with lactose observed for (R.S)-MDMA x HCI was not
      seen for the other compounds studied. The results are discussed in terms of
      hydrogen bonding and possible polymorphs. It appears that lactose affects crystal
      packing by reducing conformational rigidity so that the molecule more closely
      resembles that in solution.

PMID- 10928629
TI  - An ab initio calculation of 17O and 29Si NMR parameters for SiO2 polymorphs.
AB  - Ab initio molecular orbital calculations (Hartree-Fock, HF and density functional
      theories, DFTs) have been carried out for SiO2 polymorphs coesite, low
      cristobalite, and alpha-quartz, in order to investigate the reliability of this
      method for predicting 29Si and 17O nuclear magnetic resonance (NMR) properties of
      silicates. Oxygen- and silicon-centered clusters consisting of one (1T) to three
      tetrahedral (3T) shells (one to four atomic shells), taken from real crystal
      structure, have been investigated. It is found that for reasonable predication of
      both the 29Si and 17O chemical shifts (deltaSi and delta(i)O), the minimum
      cluster is one that gives the correct second neighbors to the nucleus of
      interest. Both the delta(i)Si and delta(i)O have reached convergence with respect
      to cluster size at the OH-terminated two tetrahedral (2T) shell (three atomic
      shells around Si and four atomic shells around O) model. At convergence, the
      calculated delta(i)Si values agree well (within +/- 1 ppm) with experimental
      data. The calculated 17O electric field gradient (EFG)-related parameters also
      agree with experimental data within experimental uncertainties. The calculation
      also reproduces small differences in delta(i)O for O sites with similar
      tetrahedral connectivities, but shows deviations up to about 10 ppm in relative
      difference for O sites with different tetrahedral connectivities. The poor
      performance for the latter is mainly due to the approximations of the HF method.
      Our study thus suggests that the ab initio calculation method is a reliable mean
      for predicting 29Si and 17O NMR parameters for silicates. Such an approach should
      find application not only to well-ordered crystalline phases, but also to
      disordered materials, by combining with other techniques, such as the molecular
      dynamics simulation method.

PMID- 10928630
TI  - Calculation of pulsed NMR signal in I = 3/2 quadrupolar spin system.
AB  - The rf pulse response of I = 3/2 spin system experiencing first order quadrupolar
      splitting is studied using density matrix approach. A general expression is
      derived in terms of spin populations, quadrupole splitting and duration and
      amplitude of the rf pulse for calculating the NMR signal arising due to the
      centre line and satellite resonances for the situation where the impressed rf
      pulse excites the resonances selectively as well as non-selectively. The
      necessary 4 X 4 transformation matrix obtained analytically by diagonalyzing the
      Hamiltonian are used to get the expression for the centre line response. The
      satellite signals are obtained in the same way but by using the numerical values
      of the roots of the related quartics. The widths of the corresponding pi/2-pulses
      are calculated for different initial spin populations. The variations of this
      pulse-width and the corresponding signal amplitude as a function of satellite
      splitting are studied.

PMID- 10928631
TI  - One- and two-dimensional 13C-1H/15N- 1H dipolar correlation experiments under
      fast magic-angle spinning for determining the peptide dihedral angle phi.
AB  - A recently proposed 13C-1H recoupling sequence operative under fast magic-angle
      spinning (MAS) [K. Takegoshi, T. Terao, Solid State Nucl. Magn. Reson. 13 (1999)
      203-212.] is applied to observe 13C-1H and 15N-1H dipolar powder patterns in the
      IH-15N- 3C- H system of a peptide bond. Both patterns are correlated by 15N-to
      13C cross polarization to observe one- or two-dimensional (1D or 2D) correlation
      spectra, which can be simulated by using a simple analytical expression to
      determine the H-N-C-H dihedral angle. The 1D and 2D experiments were applied to N
      acetyl[1,2-13C,15N] DL-valine, and the peptide q angle was determined with high
      precision by the 2D experiment to be +/- 155.0 degrees +/- 1.2 degrees. The
      positive one is in good agreement with the X-ray value of 154 degrees +/- 5
      degrees. The 1D experiment provided the value of phi = +/- 156.0 degrees +/- 0.8
      degrees.

PMID- 10928632
TI  - Determination of the (Na+) Sternheimer antishielding factor by 23Na NMR
      spectroscopy on sodium oxide chloride, Na3OCl.
AB  - The (Na+) Sternheimer antishielding factor gammainifinity (Na+) was determined by
      23Na NMR spectroscopy on sodium oxide-chloride, Na3OCl. The quadrupolar coupling
      constant of the sodium ion in Na3OCI was determined to QCC = 11.34 MHz, which
      presents the largest coupling constant of a sodium nucleus observed so far.
      Applying a simple point charge model, the largest principal value of the electric
      field gradient at the sodium site was calculated to V(zz) = -6.76762 x 10(20)
      V/m2. From these values we calculated the (Na+) Sternheimer antishielding factor
      to gammainifinity (Na+)= -5.36. In sodium oxide, Na2O, we observed an isotropic
      chemical shift of deltaCS = 55.1 ppm, referenced to 1 M aqueous NaCI (delta = 0
      ppm).

PMID- 10928634
TI  - Correlation between 31P chemical shift tensor and local structure in lithium
      cyclohexaphosphates Li6P6O18 x 3H2O and Li6P6O18.
AB  - To understand the surprising behavior between the variations of the P'-P-P"
      angles and the correlated variations of the O'-P-O" ones, two lithium
      cyclohexaphosphate compounds Li6P6O18 x 3H2O and Li6P6O18 are studied by solid
      state nuclear magnetic resonance (NMR) spectroscopy. The two compounds exhibit
      the same [P6O18]6- ring anions but with 3m or 1 internal symmetry, respectively.
      Such symmetries induce local distortions that are exhibited by NMR spectroscopy.
      One-dimensional (1D) NMR gives information on structural sites of 7Li and 31P
      ions and the crystallographic non-equivalencies are observed. Nevertheless, in
      the anhydrous compound, X-ray diffraction and NMR results do not completely agree
      and some discrepancy exists between the number of sites observed with the first
      technique and the number of lines exhibited in the NMR spectra either for 7Li or
      31P nuclei. This problem is elucidated by using 2D double quantum NMR
      spectroscopy coupled with theoretical considerations. We find that the 31P
      chemical shift tensor is dependent on the deviations of the O-P-O angles from
      those in the regular tetrahedron. Within the same empirical model, we suggest
      that the surprising behavior between the variations of the P'-P-P" and the ones
      of the O'-P-O" is related to the overall charge on the PO4 group. We also find
      the positions of the isotropic lines for 7Li essentially depend on the site co
      ordination of this nuclei.

PMID- 10928633
TI  - The 15N and 13C solid state NMR study of intramolecular hydrogen bond in some
      Schiff's bases.
AB  - A series of 11 Schiff's bases derived from substituted salicylaldehyde and
      aliphatic amines has been studied in the solid state by 15N and 13C cross
      polarization magic angle spinning (CPMAS) nuclear magnetic resonance (NMR). 15N
      CPMAS is especially useful for investigation of the tautomerism in the compounds
      considered, owing to the large difference in the nitrogen chemical shifts of OH
      and NH tautomers. In the solid state, three of the compounds examined were shown
      by 15N NMR to exist as OH tautomeric forms, and the remaining eight as the
      corresponding NH forms. This was confirmed by 13C CPMAS. The results reported
      were compared with those obtained in CDCI3 solutions.

PMID- 10928635
TI  - Powder MAS NMR lineshapes of quadrupolar nuclei in the presence of second-order
      quadrupole interaction.
AB  - We derive a complete analytical solution for the powder magic angle spinning
      (MAS) nuclear magnetic resonance (NMR) lineshape in the presence of second-order
      quadrupole interaction, considering a radiofrequency (rf) pulse of finite width,
      a finite MAS frequency, and a non-zero asymmetry parameter. (Ix) is calculated
      using two approaches. The first applies time-dependent perturbation theory in the
      presence of the rf pulse and stationary perturbation theory (SPT) in its absence.
      The second is based on the Magnus expansion of the density matrix in the
      interaction representation during the pulse and SPT in its absence. We solve the
      problem in the laboratory frame using the properties of the Fourier transform and
      spin operators. Diagonalisation is not required. Both approaches agree well with
      each other under all conditions and also with the transition probability approach
      for the central transition. The Magnus expansion exists at all times and the
      effect of the non-secular terms is negligible. We describe an analytical method
      of averaging (Ix) over the Euler angles and simulate the 11B MAS NMR lineshapes
      for crystalline and vitreous B2O3. A critical analysis is given of all earlier
      calculations of the MAS NMR lineshape.

PMID- 10928637
TI  - Anatomic origin of P13 and P14 scalp far-field potentials.
AB  - After median nerve stimulation, noncephalic or earlobe reference montages enable
      one to record over the scalp a well-defined, positive far-field response, which
      has been labeled the P14 or P13-P14 complex. It has been ascertained that this
      wave is generated in the caudal brainstem. Its use is reliable and sometimes
      mandatory in assessing a number of diseases that affect primarily the brainstem,
      such as multiple sclerosis or coma. Because of its complex shape as well as
      discrepant findings in the literature, it is still debated whether this potential
      is produced by a single or by multiple serial generators. The authors present
      these different views and summarize the different recording methods, while
      bearing in mind that some recording techniques are more suitable for routine
      purposes and others are preferred in selected cases, when more information
      regarding caudal brainstem function is required.

PMID- 10928636
TI  - Anatomic origin of the cervical N13 potential evoked by upper extremity
      stimulation.
AB  - There is a large consensus, based on converging evidence, that N13 recorded at
      lower cervical levels has a segmental postsynaptic origin in the gray matter of
      the cervical cord and that because of the orientation of its dipole field, the
      Cv6-anterior cervical derivation should be used whenever the diagnostic problem
      requires that this potential be assessed selectively in terms of latency and
      amplitude. The diagnostic utility of the lower cervical N13 recording in dorsal
      horn deafferentation and in lesions at the Cv6-Cv8 metameric levels has been
      validated in all types of cervical cord lesions. Unfortunately, such clear-cut
      conclusions do not apply to the N13 potential recorded at upper cervical levels.
      Currently, this component is not considered to provide enough reliable
      information, in addition to P13-P14 scalp recordings, to be used routinely in the
      diagnosis of cervicomedullary lesions.

PMID- 10928638
TI  - Anatomic origin and clinical application of the widespread N18 potential in
      median nerve somatosensory evoked potentials.
AB  - N18 is a broad negativity, with a duration of approximately 20 msec after
      positive far-field potentials and is recorded widely over the scalp using a
      noncephalic reference. Its origin has been controversial but its preservation
      after pontine or upper medullary lesion while loss after high cervical lesions
      suggested its medullary origin. Comparison with animal studies and direct
      recording studies in humans leads the authors to conclude that N18 is most likely
      generated at the cuneate nucleus by primary afferent depolarization. Namely,
      dorsal column afferents send collaterals to interneurons within the cuneate
      nucleus, which in turn synapse on presynaptic terminals of dorsal column fibers
      and depolarize them as a mechanism of presynaptic inhibition. In this way, an
      electrical sink is formed on presynaptic terminals, whereas their dorsocaudally
      situated axons serve as a source. The ventrorostral negative pole of the
      resultant dipolar potential must correspond to N18. The authors obtained a
      measure to evaluate medullary function objectively, and therefore N18 may be
      useful as a diagnostic tool for brain death. Usage of a C2S reference is
      essential for the accurate estimation of N18. Origins of other somatosensory
      evoked potential components related to the cuneate nucleus are also discussed.

PMID- 10928639
TI  - Neuroanatomic substrates of lower extremity somatosensory evoked potentials.
AB  - After stimulation of the lower extremity nerve (tibial nerve), N21 and N23 are
      recorded from L4 and T12 spine respectively. The far-field potentials of P31 and
      N35 are registered from Fpz-C5s (fifth cervical spine) or CPi (ipsilateral with
      respect to the side of stimulation)-ear derivation. Additional far-field
      potentials of P17 and P24 may be recorded from the scalp when a noncephalic
      (knee) reference is used. The major positive peak, P40, is registered at the
      vertex and the CPi. Preceding P40, there is a small negative peak, N37, recorded
      at the contralateral (CPc) hemisphere. Neuroanatomic substrates of these
      somatosensory evoked potential (SSEP) components are less well clarified compared
      with those of upper extremity (median nerve) SSEPs, primarily because clinical
      application of lower extremity SSEPs is more difficult, and all of the
      aforementioned potentials but one (P40) are not obligatory components. The
      concept of "paradoxical lateralization" complicates the issue further.
      Accumulating evidence, however, suggests that the far-field potentials of P17 and
      P31 arise from the distal portion of the sacral plexus and brainstem
      respectively. These correspond to P9 and P14 of the median nerve SSEPs
      respectively. The spinal potential of N23 is equivalent to the N13 cervical
      potential of the median nerve SSEP. N35 recorded from the ipsilateral hemisphere
      is analogous to N18 of the median nerve. Paradoxically lateralized P40 has been
      thought to represent the positive end of a dipole field, reflected by the
      negativity at the mesial surface of the contralateral hemisphere, and has
      commonly been considered to be equivalent to the first cortical potentials (N20)
      of the median nerve SSEP. However, more recent evidence suggests that the primary
      positivity is at the mesial cortical surface, and it more likely corresponds to
      P26 of the median nerve SSEP. Thus the first cortical potential corresponding to
      N20 is probably a small and inconsistent N37 recorded on the contralateral
      hemisphere. These assumptions need to be verified further by more extensive
      clinical studies applied to various neurologic disorders.

PMID- 10928640
TI  - Sensory and motor interfering influences on somatosensory evoked potentials.
AB  - The interfering influences by which the different components of the early
      somatosensory evoked potentials are modified are reviewed from both
      neurophysiologic and clinical perspectives. Special consideration is given to the
      specific differences between sensory and motor interferences. In this context,
      the specific effect of the mental movement simulation task on the frontal N30
      component is discussed in relation to the involvement of this evoked wave as a
      physiologic index of the dopaminergic motor pathways. Relevant interfering
      approaches, including concurrent events ranging from tactile stimulation to
      locomotion, are reviewed and discussed insofar as these data provide insights
      into the neurophysiologic processes of interaction between competing internal
      models controlling motor acts and sensory information.

PMID- 10928642
TI  - High-frequency oscillations of somatosensory evoked potentials and fields.
AB  - A short review of previous studies is presented on somatic, evoked high-frequency
      oscillations. Also described briefly is recent data on the detection of high
      frequency oscillations to posterior tibial nerve stimulation, and also on both
      tangential (area 3b) and radial (area 1) dipoles to median nerve stimulation. The
      findings show that high-frequency oscillations are not specific to median nerve
      stimulation but represent ubiquitous activity in the primary somatosensory
      cortex. Modulation of high-frequency oscillations versus electric and magnetic
      N20, N20 (m), primary response by a wake-sleep cycle, by attention or
      interference, by aging, and in central nervous system diseases such as
      Parkinson's disease and myoclonus epilepsy are also presented. Finally, a gamma
      aminobutyric acid inhibitory interneuron hypothesis is presented for high
      frequency oscillations based primarily on the findings regarding reciprocal
      modulation of the high-frequency oscillations and the underlying magnetic N20
      (N20m) by a wake-sleep cycle and by attention or interference.

PMID- 10928643
TI  - Topography of the initial cortical component of the median nerve somatosensory
      evoked potential. Relationship to central sulcus anatomy.
AB  - The initial cortical component of the median nerve somatosensory evoked potential
      (SSEP), the parietal N20, is generated in the posterior bank of the central
      sulcus and inverts in polarity across the sulcus. The inversion is used to
      identify the central sulcus. The precentral P20 is sometimes not identifiable in
      scalp recordings, and this has been attributed to a dipole orientation that
      directs the maximum positivity downward, into the brain. The authors mapped
      cortical SSEPs during resection of an arteriovenous malformation in the left
      sensorimotor area. Preoperative scalp SSEPs over the right hemisphere were normal
      with a frontal P20, but those over the left hemisphere had an unusual topography
      with a frontal N20. Intraoperative cortical surface recordings demonstrated an
      N20-P20 inversion in the inferior-superior rather than the usual posterior
      anterior direction. This was a result of the trajectory of the central sulcus
      over the surface of the brain. The section containing the hand representation was
      coursing in an anterior-posterior direction. This anatomic variant is an
      additional cause of absent frontal P20 in scalp recordings. Variations in central
      sulcus anatomy may cause unusual SSEP topographies, but two-dimensional SSEP
      mapping and correlation with the sulcal anatomy can still permit localization of
      the central sulcus in such cases.

PMID- 10928641
TI  - Pain-Related somatosensory evoked potentials.
AB  - The authors reviewed basic and clinical reports of pain-related somatosensory
      evoked potentials (SSEP) after high-intensity electrical stimulation [pain
      SSEP(E)] and painful laser stimulation [pain SSEP(L)]. The conduction velocity of
      peripheral nerves for both pain SSEP(E) and pain SSEP(L) is approximately 10 to
      15 m/second, in a range of Adelta fibers. The generator sources are considered to
      be the secondary somatosensory cortex and insula, and the limbic system,
      including the cingulate cortex, amygdala, or hippocampus of the bilateral
      hemispheres. The latencies and amplitudes are clearly affected by vigilance,
      attention-distraction, and various kinds of stimulation applied simultaneously
      with pain. Abnormalities of pain SSEP(L) reflect an impairment of pain
      temperature sensation, probably relating to dysfunction of A5 fibers of the
      peripheral nerve and spinothalamic tract. In contrast, conventional SSEP after
      nonpainful electrical stimulation reflects an impairment of tactile, vibratory,
      and deep sensation, probably relating to dysfunction of Aalpha or Abeta fibers of
      the peripheral nerve and dorsal column. Therefore, combining the study of pain
      SSEP(L) and conventional SSEP is useful to detect physiologic abnormalities, and
      sometimes subclinical abnormalities, of patients with peripheral and central
      nervous system lesions.

PMID- 10928644
TI  - Serial evoked potentials and outcome in cerebrovascular critical care patients.
AB  - Median-nerve evoked somatosensory evoked potentials (SEPs) and brainstem auditory
      evoked potentials (BAEPs), examined early in the course of patients suffering
      from cerebrovascular disease, correlate statistically significantly with outcome.
      Little is known about the changes of evoked potentials in the course of disease
      and their correlation to outcome. In a series of 215 patients (75 supratentorial
      infarctions, 36 infratentorial infarctions, 58 supratentorial hemorrhages, 18
      infratentorial hemorrhages, and 28 aneurysmatic subarachnoid hemorrhages)
      requiring neurologic intensive care treatment, we prospectively examined the
      correlation between the findings of serial SEPs and BAEPs and outcome at 4 weeks.
      Evoked potentials were examined after admission, after 1 week, and after 2 weeks.
      The findings were classified in 4 categories (normal, unilateral or bilateral
      pathologic findings, unilaterally attenuated, and bilaterally attenuated).
      Clinical outcome was determined by classification according to the Glasgow
      Outcome Scale (death, persistent vegetative state, severely incapacitated, mildly
      incapacitated, and recovery). Statistical evaluation was performed using Fisher's
      exact test for all variables. In all subgroups, SEPs correlated statistically
      significantly with outcome at all three examinations. No correlation was found
      for BAEPs at first examination in infratentorial disease, nor at second
      examination in subarachnoid hemorrhages. In all other cases, SEPs and BAEPs were
      correlated statistically significantly with outcome at all three examination
      timepoints.

PMID- 10928645
TI  - Reappraisal of filter effects on P300 voltage and latency.
AB  - The selection of which high-pass filter cutoff to use in P300 studies continues
      to be a serious methodological consideration. To determine whether there was an
      optimal range of bandpass widths-a range in which P300 voltage and latency would
      not show statistically significant differences-the authors recorded P300
      responses to the auditory "oddball" paradigm from Cz and Pz electrodes in a group
      of eight healthy males. The authors used high-pass filter cutoffs of 0.01, 0.1,
      0.3, and 1.0 Hz with low-pass filter cutoffs of 30 and 100 Hz and measured both
      P300 peak voltages and P300 integrated mean voltages at 12 bandpass settings.
      There were statistically significant differences in 7 out of 12 bandpass
      comparisons for P300 peak voltages and in 7 out of 12 bandwidth comparisons for
      P300 integrated mean voltages. For P300 latencies, there were statistically
      significant differences in 9 out of 12 bandwidth comparisons. Based on these
      results, the best recommendation, therefore, is that the high-pass filter be set
      no higher than 0.3 Hz.

PMID- 10928646
TI  - The clinical usefulness of the measurement of cytokines.
AB  - The utilization of accurate and sensitive methods for the measurement of
      cytokines in body fluids is prerequisite for the proper use of these mediators in
      clinical practice. Many factors contribute to the complexity of cytokine
      quantitation. Bioassays historically preceded immunoassays, which are now very
      popular, but there is a need for standardization. Nevertheless, due to the local
      effects of cytokines, the study of their blood levels is of limited value for an
      understanding of the pathophysiology of these mediators. This explains the
      development of alternative approaches to assess the ability of cells to produce
      cytokines. These include the Enzyme-Linked Immuno Spot Assay (ELISPOT), the
      measurement of cell-associated cytokines by flow cytometry, and the study of
      cytokine secretion by isolated peripheral blood mononuclear cells or by whole
      blood test. All these techniques, associated with a local detection of cytokines
      by immunohistochemistry or in situ hybridization and reverse transcriptase
      polymerase chain reaction, appear to be complementary tools for a better
      understanding of the biology of cytokines. Selected examples of possible clinical
      applications related to infectious diseases, cancer, autoimmune diseases,
      allergy, transplantation and preclinical evaluation of drugs and biotechnology
      products are given.

PMID- 10928647
TI  - Measurement of cholesterol and other lipoprotein constituents in the clinical
      laboratory.
AB  - Measurements of lipids and lipoproteins in the clinical laboratory have become
      increasingly important because of their predictive association with
      cardiovascular diseases, especially coronary artery disease. The US National
      Institutes of Health-sponsored National Cholesterol Education Program and
      counterparts in other countries have developed national consensus guidelines for
      diagnosis and treatment of coronary artery disease which provide risk cut-points
      and define use of the lipid/lipoprotein analytes in case finding and therapy.
      Total and low density lipoprotein cholesterol and triglycerides are measured as
      positive risk factors and high density lipoprotein cholesterol as an inverse risk
      factor for coronary artery disease. A National Cholesterol Education Program
      sponsored expert laboratory panel has developed guidelines for measurements with
      requisite analytical performance targets for total error and corresponding
      precision and bias. The US Centers for Disease Control and Prevention have
      established reference methods for total and high density lipoprotein cholesterol
      and for triglycerides, with a method for low density lipoprotein cholesterol in
      development. Standardization programs for research laboratories and a Cholesterol
      Reference Method Laboratory Network for diagnostic manufacturers and clinical
      laboratories provide reliable access and documentation of traceability to
      accepted reference methods. Methods for the lipid/lipoprotein analytes have
      improved dramatically in recent years and, coupled with improved chemistry
      analyzer systems and more attention to standardization by manufacturers, offer
      considerable improvement in analytical performance. Fully automated homogeneous
      assays for high density lipoprotein cholesterol and newer similar assays for low
      density lipoprotein cholesterol have potential for better precision as well as
      more convenient and cost-effective measurements. Attention to pre-analytical
      sources of variation is also important in making reliable classification of
      patients.

PMID- 10928648
TI  - Serum ras (p21) as a marker for occupationally derived lung cancer?
AB  - Certain subsets of the population are especially sensitive to carcinogens, and
      this can be determined using molecular biological methods. In the literature
      there has been evidence presented for the use of p21ras (ras) as a tumor marker
      for human carcinogenic substances such as asbestos, polycyclic aromatic
      hydrocarbons, and vinyl chloride in the workplace. In this study we have examined
      whether serum ras could serve as a biomarker for the early detection of
      occupationally derived lung cancer, with an emphasis on Schneeberger (radon
      induced) lung cancer. Sera were taken from 65 male tumor patients. Fifty-nine
      patients suffered from primary lung cancer (including 18 patients with
      Schneeberger lung cancer and 12 patients with asbestos-related lung cancer).
      Additionally, 29 patients with non-malignant lung disease, and a healthy control
      group (44) including 32 former uranium miners of SDAG Wismut exposed to ionizing
      radiation (radon and its decay products) were examined. Ras protein was
      determined via three different methods: 1) immunoprecipitation followed by SDS
      polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting; 2) SDS-PAGE
      using 5-17% gradient gels followed by Western blotting; 3) pre-incubation with
      Blue Sepharose, SDS-PAGE on 5-17% gradient gels, and Western blotting. The
      results show that 1 ng ras protein was measurable in serum standards. This
      protein could not be detected in patient sera or in sera from any of the study
      groups. Thus, ras cannot be considered useful as a marker for the early detection
      of asbestos-induced or Schneeberger lung cancer.

PMID- 10928649
TI  - Macro lactate dehydrogenase in a patient with myocarditis.
AB  - Elevated level of plasma lactate dehydrogenase activity in a patient with
      myocarditis was found to be due to the presence of lactate dehydrogenase
      immunoglobulin complexes in circulation. The complexes were demonstrated by
      counter-immunoelectrophoresis. In this case, three immunoglobulins (IgG, IgA and
      IgM) and two types of light chains (lambda and kappa) combined with lactate
      dehydrogenase.

PMID- 10928650
TI  - Elimination of serum complexed prostate-specific antigen after radical retropubic
      prostatectomy.
AB  - Total prostate-specific antigen (PSA) and complexed PSA were determined in venous
      blood from 12 patients with prostate cancer before and after radical
      prostatectomy by using Immuno 1 PSA assays. The elimination kinetics of complexed
      PSA were compared with that of total PSA. Nearly constant concentrations of
      complexed PSA were found during the first six hours after surgery, in contrast to
      the rapid elimination of free PSA and the significant decrease of total PSA. From
      day one to ten there was a continuous and nearly identical decrease of complexed
      PSA compared to total PSA. Our findings suggest that the initial rapid decrease
      of free PSA immediately after operation could be caused by formation of new PSA
      complex.

PMID- 10928651
TI  - Suitability of collection tubes with separator gels for collecting and storing
      blood samples for therapeutic drug monitoring (TDM).
AB  - In this study, we present significant changes occurring in serum drug
      concentrations while using blood collection tubes that contain a barrier gel.
      This report also contains results with antidepressant drugs, which have not been
      studied before with human samples. The drug concentrations were measured either
      with high performance liquid chromatography (HPLC) or fluorescence polarization
      immunoassay (FPIA). The results show that gel tubes are suitable for blood
      collection for antiepileptic, antibiotic, asthma and cardioactive drug
      measurements, since only slight adsorption was seen (0-5%). However, the studied
      tubes are not suitable for blood collection of antidepressants nor
      benzodiazepines, because the adsorption can be 5-30%. The adsorption was even
      higher (up to 40%) when samples were stored for 24 h after centrifugation in gel
      tubes. When the centrifugation step was performed after storage the effect of the
      barrier gel was lower (only 0-13%). Antidepressant drug measurements performed
      from patient specimens collected in the studied gel tubes and stored for 3 h
      showed <10% adsorption of the studied drugs. After 24 h storage time,
      concentrations of all analysed drugs decreased even more: adsorbed amount of
      drugs were about 5-20%. The studied gel tubes are proposed to be satisfactory for
      blood collection for antidepressant drug measurements if separation step is
      performed within 3 h after blood clotting. With the spiked samples the adsorption
      to barrier gel was higher, so it seems that adsorption is faster when drugs are
      not highly bound to serum proteins.

PMID- 10928652
TI  - Influence of in vivo hemoglobin carbamylation on HbA1c measurements by various
      methods.
AB  - Increased carbamylated hemoglobin formed in erythrocytes during uremia may
      interfere with HbA1c assays, but few studies compared directly both parameters.
      We measured carbamylated hemoglobin by HPLC in 45 non-diabetic uremic patients
      (16 with acute and two with chronic renal failure, 27 with transplant recipients)
      as 57.8 +/- 22.3 microg carbamylvaline/g Hb (mean +/- standard deviation) vs.
      31.6 +/- 5.1 in 15 controls (+83%, p < 0.001). In these samples, HbA1c was
      evaluated by three ion-exchange HPLC methods, 1: Diamat (BioRad), 2: A1c2.2
      (Tosoh) and 3: HA8140 (Menarini), and one immunoassay method (Tinaquant II
      Roche). Whichever the method, mean HbA1c values obtained increased in patients
      with high (> 60 microg carbamylvaline/g Hb) vs. low (< 45) carbamylated
      hemoglobin values (+0.08 to 0.25% of total Hb), but differences were not
      significant. Minor peaks on the chromatograms were however increased in parallel
      to carbamylated hemoglobin. HbA1c values over 6% were found in 4, 1, 2 and 0
      samples, with HPLC 1, 2, 3 and immunoassay, respectively. Fructosamine values
      were not significantly altered. Our results show that Hb adducts, whether due to
      carbamylation or to other chemical reactions, interfere to a variable extent with
      different HbA1c assay methods, and confirm that HbA1c values should be
      interpreted with caution in uremic patients.

PMID- 10928653
TI  - Comparison of the Abbott IMx and a high-performance liquid chromatography method
      for measuring total plasma homocysteine.
AB  - The determination of the total concentration of plasma homocysteine is of
      interest in a variety of clinical circumstances, especially, in the evaluation of
      the risk of cardiovascular disease. However, most of the methods available to
      date, many of them chromatographic, are not well suited for the majority of
      clinical laboratories. Several automated methods are now or will be, shortly,
      commercially available. We have compared one of them, the fluorescence
      polarization immunoassay (FPIA) adapted to the IMx analyzer (Abbott
      Laboratories), with the high-performance liquid chromatography (HPLC) method with
      fluorescent detection currently used in our laboratory. The results show that the
      FPIA-IMx method is less imprecise and slightly more sensitive than the HPLC. The
      comparison of 67 clinical plasma specimens indicated that there is a proportional
      error disagreement between FPIA-IMx and HPLC (FPIA=1.19 HPLC + 0.92; confidence
      region for slope and y-intercept were, respectively, from 1.06 to 1.31 and from 
      0.06 to 2.32). The nature of this error is not explained by the experiments
      performed to study the inaccuracy of both methods, which included the
      investigation of dilution parallelism, analytical recovery and cross-reactivity.
      The different results of homocysteine concentration obtained with FPIA-IMx and
      HPLC must be taken into account when a change of methodology is under
      consideration.

PMID- 10928654
TI  - Evaluation of the ADVIA Centaur TSH-3 assay.
AB  - An analytical evaluation of the thyroid stimulating hormone (TSH-3) assay on the
      Bayer ADVIA Centaur immunoassay system was performed. General analytical
      requirements (linearity, resistance to typical interferences, absence of a carry
      over effect) were fulfilled and reproducibility was satisfactory. Inter-assay
      coefficient of variation (CV) of a human serum pool with a concentration of 0.014
      mU/l was 22.3%; at concentrations between 0.26 and 83 mU/l CV was below 6%.
      Method comparison study demonstrated close agreement of TSH results compared to
      those obtained with the Roche Elecsys 2010 TSH assay (ADVIA Centaur = 1.08 x
      Elecsys - 0.18 mU/l; r=0.987; n=324). Handling and practicability of the ADVIA
      Centaur system proved to be convenient with a very high sample throughput. We
      conclude that the ADVIA Centaur TSH-3 assay meets requirements for clinical use.

PMID- 10928655
TI  - Biochemical composition and electrolyte balance of "unstimulated" whole human
      saliva.
AB  - The biochemical composition of "unstimulated" whole saliva was determined in
      healthy adult subjects. Based on their relative concentration, salivary analytes
      could be classified into three arbitrary categories: concentration lower than in
      serum (saliva/serum ratio < 0.5; 12 analytes), similar to serum (ratio = 0.5-1.5;
      five analytes), and higher than in serum (ratio > 1.5; five analytes). Consistent
      with local production, an elevated lactate dehydrogenase (LDH) activity in the
      saliva was associated with a non-serum like LDH isoenzyme pattern: LDH5 >> LDH4 >
      LDH3 >> LDH2 > LDH1. Compared with serum, the concentrations of hydrogen (as
      reflected in the pH), potassium and inorganic phosphorus were much higher
      (saliva/serum ratio > or = 3), whereas that of sodium, total magnesium, chloride,
      and total carbon dioxide were lower (saliva/serum ratio < or = 0.3). The
      concentration of ionized calcium was similar in saliva and serum (saliva/serum
      ratio = 0.8), while ionized magnesium was unmeasurable in saliva. The salivary
      ionized calcium fraction was higher (0.76) than previously suggested (0.51). The
      difference between the main salivary cations (potassium, sodium), and anions
      (phosphate, chloride) was similar to serum (anion gap: 4 vs. 11 meq/l). Highly
      significant (p < or = 0.012) correlations occurred among salivary pH,
      dihydrophosphate, total calcium, and potassium. Our data suggest that calcium,
      potassium, chloride and phosphates are the major salivary complex-forming ions.
      The major compositional differences between serum and saliva show that saliva is
      not a passive "ultrafiltrate" of serum and salivary constituents may play a
      distinct physiological role.

PMID- 10928656
TI  - Evaluation of a new simple and rapid enzyme-linked immunosorbent assay kit for
      neopterin determination.
AB  - A new commercially available enzyme-linked immunosorbent assay (ELISA) kit has
      been evaluated for the measurement of neopterin concentrations in serum, plasma
      and urine. This competitive ELISA is technically simple, requires only small
      sample volume and is rapid to perform. The assay procedure consists of sequential
      1.5 h and 10 min room temperature incubation steps. The ELISA is accurate,
      sensitive, specific, and precise. Linear regression analysis of neopterin
      concentrations measured with the new ELISA and with an established method yielded
      a highly significant correlation (r = 0.99). The new assay is applicable to ELISA
      workstations, thus enabling determination of neopterin in large series of
      samples. The neopterin ELISA kit has been used in routine laboratory testing of
      blood donations in a blood bank.

PMID- 10928657
TI  - Analytical and clinical evaluation of troponin I determination on dimension RXL
      HM.
AB  - The evaluation of cardiac troponin I (cTnI) on the Dimension RxL-HM analyzer is
      presented. The one-step enzyme immunoassay is based on two cTnI specific
      monoclonal antibodies. Performed on a separate module of the analyzer, assay-time
      is 17 minutes. Using as criterion a between-run impression CV <20% the functional
      limit of detection was set at 0.1 microg/l. Cutoff level for minor myocardial
      damage of 0.1 microg/l was found. In Duchenne's dystrophy, patients showed
      increased cardiac Troponin T (cTnT) but no increased cTnI. In patients with a
      history of coronary heart disease undergoing chronic hemodialysis, cTnT and cTnI
      were increased. In different patients with submassive pulmonary embolism,
      increased cTnI was determined. In coronary artery bypass surgery without
      perioperative myocardial infarction, patients with extracorporeal circulation
      showed significantly higher cTnI at 24 h after surgery than those with minimal
      cardiac surgery. In patients with unstable angina, increased cTnI was found more
      often than on Stratus analyzer. In conclusion, the new assay is a very sensitive
      cTnI assay, fast and easy to perform in parallel to enzyme and substrate assays.

PMID- 10928658
TI  - Use of ion-selective electrodes for blood-electrolyte analysis. Recommendations
      for nomenclature, definitions and conventions. International Federation of
      Clinical Chemistry and Laboratory Medicine (IFCC). Scientific Division Working
      Group on Selective Electrodes.
AB  - This paper will familiarize the reader with the terms used to describe the
      behavior of ion-selective electrodes, particularly in relation to their use in
      clinical chemistry for determination of blood electrolyte cations. It serves as
      an introduction to a series of papers dealing with important cations in blood,
      namely calcium, sodium, and potassium. The detailed relationships between the ion
      activity determined by means of ion-selective electrode potentiometry in
      undiluted specimens, and the total substance concentration measured by flame
      atomic-emission spectrometry are described by flow chart and equations. Adoption
      of a convention for reporting results is recommended. The Working Group on
      Selective Electrodes has taken into account recent revisions of IUPAC
      recommendations on nomenclature and selectivity coefficient determinations for
      ion-selective electrodes, and benefited from the experience of a member of the
      WG, who was also involved in the IUPAC discussions. Nomenclature for determined
      quantities follows previous IUPAC/IFCC joint recommendations.

PMID- 10928659
TI  - FESCC survey on accreditation and post-graduate training in clinical chemistry in
      European countries. Federation of European Societies of Clinical Chemistry.
AB  - Promotion of the professional growth and development of specialists in the field
      of clinical chemistry in European countries, and harmonisation of quality
      assessment and accreditation procedures are listed among the main goals and
      activities of Federation of European Societies of Clinical Chemistry (FESCC),
      according to its 1999-2000 strategic plan. The European countries that are
      members of the European Union are in the process of establishing the "European
      Register for Clinical Chemists", based on minimum standards of education,
      training and experience as defined by the European Communities Confederation of
      Clinical Chemists (EC4). Many other European countries would like to adapt their
      system of professional education to this model. Data on post-graduate training in
      EC4 FESCC members have already been gathered in 1998. However, at the present
      time, there is no detailed knowledge of pre- and post-graduate professional
      education of specialists in clinical chemistry in the non-EC4 European countries.
      FESCC launched a survey in July 1998 in order to gather this information with the
      hope to start a database about existing systems. All FESCC members received the
      same questionnaire on accreditation (seven questions) and non-EC4 FESCC members
      received an additional questionnaire with 11 questions related to post-graduate
      training in clinical chemistry. The response rate of the 35 FESCC member
      countries was 93% from the 15 EC4 members (14 responses/15 countries) and 80%
      from the 20-non-EC4 (16 responses/20 countries). The heterogeneity of the data on
      post-graduate training in clinical chemistry indicates that a great effort will
      be needed before harmonisation is reached. These results, however, will provide
      an interesting basis for further discussion and promotion of post-graduate
      training in clinical chemistry. The data provided on accreditation show that the
      total number of accredited laboratories was relatively low in EC4 countries and
      even lower in non-EC4 members. It was not surprising to see that the number of
      accredited laboratories was the highest in the two countries which started
      accreditation the earliest (i.e. Sweden and UK, 1992). This situation, however,
      is changing at a fast rate in most countries and the number of the accredited
      sites is expected to increase rapidly in the next few years.

PMID- 10928660
TI  - Clinical use of soluble transferrin receptor.

PMID- 10928661
TI  - Macro creatine kinase type 1: a clinically significant marker?

PMID- 10928662
TI  - Postoperative refractive error after simultaneous vitrectomy and cataract
      surgery.
AB  - PURPOSE: To evaluate the effect of vitrectomy on postoperative refraction after
      simultaneous vitrectomy and cataract surgery. METHODS: We compared the spread
      between predicted and actual refractions in 206 eyes after a simultaneous
      vitrectomy, phacoemulsification, aspiration and acrylic lens insertion (combined
      surgery group), and in 67 eyes after cataract surgery only (cataract surgery
      group) as control. A vitrectomy was performed for diabetic retinopathy in 127
      eyes, macular hole in 32 eyes, rhegmatogenous retinal detachment in 16 eyes,
      branch retinal vein occlusion in 15 eyes, and other conditions in 26 eyes. In the
      combined surgery group, 79 eyes had a gas tamponade after insertion of the
      intraocular lens. RESULTS: The spread between predicted and actual refractions
      was - 0.05 +/- 1.18 diopters (average +/- SD) in the combined surgery group and
      +0.55 +/- 1.32 D in the cataract surgery group. The actual refractive errors in
      the combined surgery group were found to shift toward myopia when compared with
      the controls. Among the combined surgery group, 127 eyes without a gas tamponade
      showed a postoperative refractive error of +0.14 +/- 1.11 D, while 79 eyes with a
      gas tamponade demonstrated an error of -0.36 +/- 1.22 D. CONCLUSIONS: Use of a
      gas tamponade in the combined surgery group increased the myopic change and was
      thought to have pressed the intraocular lens forward.

PMID- 10928663
TI  - Choroidal detachment after vitreous surgery.
AB  - BACKGROUND AND OBJECTIVE: To study the frequency and clinical features of
      choroidal detachment (CD) after vitreous surgery, because there have been no
      reports on this problem. PATIENTS AND METHODS: We studied the clinical features
      of 14 patients (15 eyes) with CD from a total of 380 patients treated with
      vitrectomy at the Nagasaki University Hospital from January 1994 to August 1997.
      RESULTS: The incidence of CD after vitreous surgery was 3.9% (15/380). The
      reasons for vitrectomy were 6 retinal detachments, 4 proliferative diabetic
      retinopathies, and 5 others. During vitrectomy, 4 eyes were treated with scleral
      buckling, 11 with endolaser photocoagulation, and 3 with cryoretinopexy. Retinal
      detachment as a postoperative complication was seen in 8 patients, and in 5 of
      them the retina remained detached after the final treatment. CONCLUSIONS: CD may
      be caused by scleral buckling, panphotocoagulation, or stress on the ciliary
      body. Some patients with CD have a poor outcome.

PMID- 10928664
TI  - Aqueous flare elevation in the fellow eye after vitrectomy.
AB  - OBJECTIVE: Aqueous flare elevation has been shown to occur in the fellow eye
      after cataract surgery. This study tests whether such subclinical sympathetic
      reaction also takes place after vitrectomy. PATIENTS AND METHODS: In a
      prospective clinical study, preoperative and postoperative 2-week levels of
      aqueous flare in the fellow eyes of 38 patients who underwent vitrectomy during a
      6-month period were measured with a laser flare-cell meter. RESULTS: Aqueous
      flare levels in the fellow eyes 2 weeks after vitrectomy (mean, 15.70 photon
      counts/millisecond) were significantly higher than preoperative flare levels
      (mean, 11.78 photon counts/millisecond, Wilcoxon's signed rank test, P = 0.04).
      CONCLUSION: This study demonstrated that subclinical sympathetic reaction did
      occur in the fellow eyes after vitrectomy.

PMID- 10928665
TI  - Visual improvement after removal of submacular exudates in patients with diabetic
      maculopathy.
AB  - OBJECTIVE: To improve the central visual function of eyes affected by massive
      hard exudates in cases of diabetic maculopathy. PATIENTS AND METHODS: Six eyes of
      4 patients with diabetic maculopathy were treated by pars plana vitrectomy for
      massive retinal exudates persisting for more than 3 months. The massive hard
      exudates were removed from the subretinal space with subretinal forceps. We
      evaluated the visual acuity of these eyes 6 months after surgery. RESULTS:
      Following the removal of the hard exudates, visual acuity improved in all eyes.
      Massive hard exudates were mainly located in the subretinal space and were
      removable using subretinal forceps. No serious postoperative complications
      occurred. The removed tissues consisted of macrophages laden with many cholestrin
      crystals and lipid droplets, as well as fibrous tissues. CONCLUSION: We concluded
      that central visual function can be improved by removing subretinal exudates
      surgically.

PMID- 10928666
TI  - Combined modified grid and panretinal photocoagulation for diffuse diabetic
      macular edema and proliferative diabetic retinopathy.
AB  - PURPOSE: To determine the effectiveness of combined macular modified grid and
      peripheral panretinal photocoagulation in diabetic eyes with both macular edema
      and proliferative retinopathy. MATERIAL AND METHODS: We evaluated 52 eyes with
      diffuse diabetic macular edema and proliferative diabetic retinopathy. Treatment
      was performed in two sessions consisting of initial modified grid to the macula
      and panretinal photocoagulation to the inferior half of the peripheral retina,
      followed 2 to 4 weeks later by panretinal photocoagulation to the superior half.
      RESULTS: At one year, visual acuity was improved in 8%, stable in 79%, and worse
      in 13%. At two years, visual acuity was improved in 4%, stable in 72%, and worse
      in 24%. Macular edema resolved in 43 of 46 eyes (93%), and proliferative
      retinopathy was reduced in 25 of 29 eyes (86%) at last examination. CONCLUSION:
      Combined macular modified grid and peripheral panretinal photocoagulation is an
      effective treatment approach in diabetic eyes with both macular edema and
      proliferative retinopathy. Laser photocoagulation in those diabetic eyes with
      diffuse diabetic macular edema and proliferative diabetic retinopathy can be
      completed in less number of treatment sessions with this method, compared to
      conventional treatment techniques.

PMID- 10928667
TI  - Low-dose intraoperative mitomycin-C versus conjunctival autograft in primary
      pterygium surgery: long term follow-up.
AB  - PURPOSE: To evaluate and compare the long term safety and efficacy of low-dose
      intraoperative application of mitomycin-C (0.02%) with conjunctival autograft in
      primary pterygium surgery. PATIENTS AND METHODS: Of 37 consecutive patients 41
      eyes with primary pterygium underwent pterygium excision with either
      intraoperative mitomycin-C (0.02%) (Group I) or conjunctival autografts (Group
      II) at random. Mitomycin-C (0.2 mg/mL) was applied for 2.5 minutes on the scleral
      bed under the conjunctiva. Conjunctival autograft was obtained from upper
      temporal limbus and secured with 10-0 monofilament nylon. The follow-up period
      ranged from 14 to 54 months (mean 36 months) for mitomycin-C group and 13 to 58
      months (mean 38 months) for conjunctival autograft group. RESULTS: Twenty-one
      eyes underwent pterygium excision with intraoperative mitomycin-C (0.02%)
      application (Group I) and 20 eyes were treated using conjunctival autograft
      (Group II). The mean size of the pterygium was 3.80 mm (range 2.6 to 4.8 mm) in
      the mitomycin-C group and 3.60 mm (range 2.5 to 4.5 mm) in the conjunctival
      autograft group. Two (9.52%) eyes treated with intraoperative mitomycin-C had
      delayed epithelial healing of corneoscleral wound and one (4.76%) eye developed
      pyogenic granuloma. Three (14.3%) of the 21 eyes in Group I and one (5%) of 20
      eyes in Group II had recurrence of pterygium (P = 0.3174). All recurrences
      occurred in patients below 40 years of age (P = 0.0384). CONCLUSION: We conclude
      that conjunctival autograft and intraoperative mitomycin-C are both equally
      effective adjuncts to primary pterygium surgery on long term follow-up. However,
      future prospective studies with larger numbers of subjects may be carried out to
      find out the optimum concentration and duration of intraoperative mitomycin-C
      application.

PMID- 10928668
TI  - Effect of 0.2% brimonidine in preventing intraocular pressure elevation after
      Nd:YAG laser posterior capsulotomy.
AB  - BACKGROUND AND OBJECTIVE: To determine the prophylactic effect of 0.2%
      brimonidine in reducing the elevated intraocular pressure (IOP) in patients
      undergoing Nd:YAG laser posterior capsulotomy. PATIENTS AND METHODS: The 81
      patients (81 eyes), who underwent Nd:YAG laser posterior capsulotomy, were
      allocated to two treatment groups. One drop of 0.2% brimonidine or vehicle was
      instilled 1 hour preoperatively and one drop immediately after capsulotomy. IOPs
      were measured preoperatively and 1, 2, 3, and 24 hours postoperatively. RESULTS:
      Intraocular pressure decreased from the baseline in the brimonidine group by the
      third postoperative hour (P<0.05), while the vehicle group exhibited an increase.
      Intraocular pressure elevations of 5 mm Hg or greater occurred in 7.3% (3/41) in
      the brimonidine group compared to 20.0% (8/40) in the vehicle group. IOP
      elevations of 10 mm Hg or greater occurred in 2.4% (1/41) in the brimonidine
      group compared to 7.5% (3/40) in the vehicle group. CONCLUSIONS: One drop of 0.2%
      brimonidine instilled 1 hour preoperatively and immediately after capsulotomy was
      found to be efficacious and safe in preventing IOP elevations that frequently
      follow Nd:YAG laser posterior capsulotomy.

PMID- 10928669
TI  - Developments in laser trabeculoplasty.

PMID- 10928670
TI  - Threshold and retreatment parameters of NPe6 photodynamic therapy in retinal and
      choroidal vessels.
AB  - BACKGROUND AND OBJECTIVE: To determine the threshold fluence for producing
      choroidal and retinal vascular occlusion with mono-L-aspartyl chlorin e6 (NPe6)
      photodynamic therapy (PDT) during primary treatment and the effect of
      retreatment. METHODS: Primary treatment: Rats, rabbits, and monkeys underwent
      NPe6 PDT to determine the threshold fluences for choroidal and retinal vessel
      occlusion. The threshold was determined by analyzing fluorescein angiograms for
      areas of nonperfusion. Retreatment: Dutch-belted rabbits underwent NPe6 PDT
      followed by fluorescein angiography. Rabbits were retreated one week later at the
      same parameters. RESULTS: Fluence levels and vascular damage thresholds were
      always higher for retinal than for choroidal vascular occlusion. Retreatment
      caused choroidal vessel closure at all tested fluences but retinal capillaries
      closed only at a fluence > 17.7 J/cm2. CONCLUSION: NPe6 PDT has a lower threshold
      to occlude choroidal vessels than retinal vessels. The cumulative effect of
      retreatment does not damage retinal vessels unless the threshold is exceeded
      during a single retreatment session.

PMID- 10928671
TI  - Disintegration of the inferior rectus muscle during strabismus surgery for
      restrictive hypotropia.
AB  - We describe a case of disintegration of the inferior rectus muscle during routine
      strabismus surgery for restrictive hypotropia after cataract surgery. We used
      this surgical approach to repair the complete infraduction deficit incurred from
      the injury.

PMID- 10928672
TI  - Macular changes in type I Gaucher's disease.
AB  - The authors illustrate the spectrum of Gaucher's disease involving the eye in the
      case of a 51-year-old man suffering from Type I Gaucher's disease who presented
      with unusual macular changes. This is the first report of chronic adult non
      neuronopathic disease (Type I) with a plaque-like mass at the fovea. Our
      hypothesis is that the lesion at the fovea is probably an aggregation of
      Gaucher's cells.

PMID- 10928673
TI  - Transpupillary thermotherapy for retinal capillary hemangioma in von Hippel
      Lindau disease.
AB  - Retinal capillary hemangiomas are a common manifestation of von Hippel-Lindau
      disease. We report the treatment of a peripapillary retinal capillary hemangioma
      in the left eye of a 30-year-old woman with this condition, using infrared diode
      laser transpupillary thermotherapy (TTT). The hemangioma was evaluated before and
      after treatment by ophthalmoscopy, fundus fluorescein angiography, and Doppler
      ultrasonography. Infrared diode laser TTT was delivered over 3 sessions during a
      period of 22 weeks, resulting in an improvement in visual acuity from counting
      fingers to 6/24 and a marked decrease in exudates surrounding the hemangioma.
      Doppler ultrasonography demonstrated a decrease in intralesional blood flow from
      7 cm per second to less than 3 cm per second, together with a decrease in the
      size of the lesion. Infrared diode laser TTT provides a useful modality in the
      treatment of retinal capillary hemangiomas, and may be particularly favorable for
      peripapillary lesions because of its relatively nondestructive characteristics.

PMID- 10928674
TI  - Suprachoroidal hemorrhage during silicone oil removal in Marfan syndrome.
AB  - A 30-year-old male with Marfan syndrome underwent pars plana lensectomy and
      vitrectomy combined with silicone oil injection for the treatment of retinal
      detachment with proliferative vitreoretinopathy (PVR). Four months after
      vitrectomy, the silicone oil was removed using an anterior chamber maintainer
      (AC) and a self-sealing clear corneal incision at the upper temporal quadrant.
      Suprachoroidal hemorrhage (SCH) developed at the end of the operation. It was
      limited to the nasal side of the retina. Suprachoroidal hemorrhage remained to be
      limited and did not show progression.

PMID- 10928675
TI  - Intramuscular lipoma of the eyelid.
AB  - To report a unique case of intramuscular lipoma of the eyelid and to alert
      surgeons to this entity that simulates a common dermoid cyst. A slowly-growing
      mass of the upper eyelid was excised from a 62-year-old man. Histology showed
      mature lipocytes interspersed with skeletal muscle. To our knowledge, this case
      represents the first report of intramuscular lipoma of the eyelid. Lipomas,
      including the intramuscular variety, are common tumors elsewhere in the body. The
      differential diagnosis of eyelid masses should include this entity.

PMID- 10928676
TI  - Inadvertent corneal indentation can cause artifactitious widening of the
      iridocorneal angle on ultrasound biomicroscopy.
AB  - A 70-year-old Asian female with narrow angles underwent ultrasound biomicroscopy
      (UBM) darkroom provocative testing. The angle was narrow under light conditions
      and occluded in the dark, except for the inferior quadrant where the angle was
      wide and the iris concave. This was reproducible in four quadrants with the use
      of a small UBM eye cup but not the large one. A small eye cup can indent the
      cornea, resulting in artifactitious angle widenening. Care must be taken when
      using the small eye cup not to press on the cornea.

PMID- 10928678
TI  - A new technique for retrieval or repositioning of damaged or migrated silicone
      punctal plugs.
AB  - A new technique for retrieval or repositioning of migrated or malpositioned
      silicone punctal plugs is described. Malposition is known to occur secondary to
      either spontaneous migration or forceful insertion. This technique offers
      considerable advantages over current treatment options including simplicity and
      minimal trauma to both the plug and the nasolacrimal system.

PMID- 10928677
TI  - Cyclodialysis cleft diagnosed by conventional ultrasonography.
AB  - This case report describes the diagnosis and management of a traumatic
      cyclodialysis cleft, in the absence of newer investigating modalities like
      ultrasonic biomicroscopy (UBM). This entity is frequently difficult to recognize
      clinically owing to the extreme hypotony and media haze that these patients
      usually present with, which makes gonioscopy particularly taxing. Adding to the
      diagnostic dilemma is the difficulty in delineating the lesion ultrasonically due
      to the extreme anterior location of the cleft. In these situations, high
      frequency ultrasound has been found to be extremely helpful, but the availability
      of such sophistication is difficult. Presented here is demonstration of the cleft
      with a microconvex ultrasound probe of 9 MHz frequency. The patient was
      successfully managed conservatively. This modality could prove to be a valuable
      adjunct to the diagnosis of such cases even in the situations of nonavailability
      of high frequency ultrasonography.

PMID- 10928679
TI  - The effect of signal grass (Brachiaria decumbens) on drug-metabolizing enzymes in
      sheep and comparison with normal cells.
AB  - The effect of Brachiaria decumbens (signal grass) on drug-metabolizing enzymes
      was studied in sheep. After 14 d of grazing a pure signal grass pasture,
      significant declines were observed in hepatic aminopyrine N-demethylase and
      aniline 4-hydroxylase (phase I biotransformation) and in conjugative enzymes UDP
      glucuronyltransferase and glutathione S-transferase. Kidney enzymes were
      significantly decreased except for UDP-glucuronyltransferase. Enzyme activities
      were also compared for normal sheep and cattle livers and kidneys. Lower
      activities were found in cattle, indicating that factors other than
      biotransformation are responsible for the clincial tolerance of cattle to B.
      decumbens toxicity.

PMID- 10928680
TI  - Influence of 3-methylcholanthrene pretreatment on sanguinarine toxicity in mice.
AB  - We examined the effect of 3-methylcholanthrene (3-MC) on the liver toxicity of
      sanguinarine in mice. Administration of 10 mg sanguinarine/kg bw ip to male mice
      resulted in significant decreases in liver glutathione and P450 enzymes
      activities, and increased in sorbitol dehydrogenase and alanine aminotransferase
      levels in serum suggestive of liver damage. However, pretreatment with 20 mg 3
      MC/kg/d ip, an inducer of P450 enzymes, for 3 d mitigated the sanguinarine toxic
      effects suggesting 3-MC induced cytochrome P450 enzymes that promote
      detoxification of sanguinarine.

PMID- 10928682
TI  - Cytotoxic and immunomodulative effects of flunitrazepam, zipeprol and
      trihexyphenidyl on human peripheral blood lymphocytes.
AB  - The cytotoxic effects of flunitrazepam, zipeprol and trihexyphenidyl on cell
      viability of peripheral blood mononuclear cells from healthy volunteers were
      studied at concentrations from 10(-2) to 10(-8) M by 2 colorimetric in vitro
      assays: the neutral red uptake assay and thiazolyl blue tetrazolium bromide
      assay. All tested drugs of abuse were non-cytotoxic at concentrations lower than
      10(-5) M. Possible immunomodulative effects of these substances were evaluated
      through phytohemagglutinin induced lymphocyte proliferation ([3H]-thymidine DNA
      incorporation assay) and by a 51Cr release natural killer assay. The 3 drugs
      studied produced statistically significant immunomodulative alterations on both
      immunological parameters.

PMID- 10928681
TI  - Effect of subacute swainsonine (locoweed; Oxytropis sericea) consumption on
      immunocompetence and serum constituents of sheep in a nutrient-restricted state.
AB  - The subacute dose-response effects of swainsonine (SW) consumption on
      immunocompetence and serum constituents of sheep in a nutrient-restricted state
      were investigated. Sheep (23 wethers, 5 ewes) were assigned to 1 of 5 SW
      treatments (0, 0.2, 0.4, 0.8, or 1.6 mg swainsonine/ kg bw/d). Swainsonine was
      delivered by feeding locoweed (Oxytropis sericea) with grama grass and alfalfa
      hays for a 28-d treatment period followed by a 21-d recovery period without
      locoweed. Body weights were measured weekly and behavioral changes were monitored
      for clinical signs of SW toxicity. Venous blood was collected weekly for
      lymphoblastogenesis and serum constituent analyses. Clinical signs (sluggishness,
      decreased responsiveness) of swainsonine toxicity were observed from d 14 to 35
      in the 0.8 and 1.6 mg treatments. Subacute oral exposure did not appear to affect
      lymphoblastogenic analyses. Acute and subacute alterations in various serum
      constituents did indicate subclinical effects of SW ingestion. Linear, quadratic
      and cubic dose-response relationships were detected for some serum constituents
      (e.g., alkaline phosphatase, aspartate aminotransferase). Subacute SW consumption
      at the levels investigated does not seem to affect the immunocompetence of
      nutrient restricted sheep. The lack of change in serum alkaline phosphatase at
      the 0.2 mg SW/kg bw/d dose indicates the potential for a no adverse effect level
      of SW consumption in nutrient restricted sheep. In combination with measurable SW
      in serum, rises in serum alkaline phosphatase and aspartate aminotransferase
      activities, and declines in serum Fe and cholesterol during subacute exposure to
      SW establish these markers as potential indicators of subclinical SW toxicosis.

PMID- 10928683
TI  - Inhibition of mitochondrial succinate oxidation by antipsychotic medication.
AB  - Fourteen antipsychotics of 5 different chemical classes were tested for their
      effects on mitochondrial succinate oxidation. Each of the compounds tested, with
      the exception of haloperidol, phenothiazine and prochlorperazine, inhibited
      succinate oxidation. The apparent inhibition constant for phenothiazine
      derivatives declined with increasing values of the partition coefficient.

PMID- 10928684
TI  - Effect of diacetylmonoxime on blood enzymes in fenitrothion-dosed buffalo calves.
AB  - The effect of iv diacetylmonoxime (DAM) alone or in combination with atropine was
      determined on blood enzymatic activities in fenitrothion-exposed buffalo calves.
      Fenitrothion given po at 435 mg/kg bw produced pronounced inhibition of blood
      acetylcholinesterase (AChE) and elevation in serum aspartate and alanine
      aminotransferases, acid and alkaline phosphatases, and lactate dehydrogenase
      within 30 min. The administration of DAM alone or in combination with atropine
      significantly reactivated AChE activity. The administration of DAM + atropine
      decreased serum aspartate and alanine aminotransferase enzymes within 1-3 d. The
      reversal effect of DAM + atropine on serum phosphatases and lactate dehydrogenase
      was greater than that of DAM or atropine alone.

PMID- 10928685
TI  - Acetyl- and pseudo-cholinesterase activities of plasma, erythrocytes, and whole
      blood in male beagle dogs using Ellman's assay.
AB  - Organophosphate and carbamate ester insecticides, main causes of pesticide
      poisoning, inhibit cholinesterase (ChE) enzymes. The aim of this study was to
      measure and compare baseline values for pseudocholinesterase and
      acetylcholinesterase (AChE) enzyme activities of different blood fractions in the
      dog to aid in diagnosis of anticholinesterase poisoning. After collecting blood
      samples from 23 6-24-mo-old male beagle dogs, Ellman's colorimetric assay was run
      on plasma, red blood cells (RBC), and whole blood fractions prepared in
      triplicate. The procedure described in a commercially available kit was applied
      to plasma and RBC. Hemolyzed whole blood fractions (final dilution 1:8) avoided
      the time-consuming and laborious separation of plasma and RBC. In addition to the
      kit substrate acetylthiocholine (ASCh), we used butyrylthiocholine (BSCh) as
      substrate. Whatever the substrate, ChE activity was lower in RBC than in other
      blood preparations. It was higher when using ASCh rather than BSCh as substrate
      (mean IU/L+/-SD): 563+/-144 and 303+/-45 respectively, in contrast to plasma
      (1640+/-310 and 2510+/-450). Whole blood enzyme activity did not differ
      significantly according to substrate: ASCh, 1590+/-190; BSCh, 1620+/-250) with a
      2 to 3% within-day coefficient of variation. Enzyme activity was significantly
      lower in dogs <1-y old. This study confirms the low ChE activity in dog RBC
      compared to other species and other blood fractions. It shows that using whole
      blood instead of separating RBC from plasma minimizes the variability of ChE
      activity in the hemoglobin-rich fraction.

PMID- 10928686
TI  - Baccharis megapotamica var Weirii poisoning in Brazilian cattle.
AB  - Three Holstein heifers died after consumption of Baccharis megapotamica var
      weirii in southern Brazil. Main histologic lesions included degeneration and
      necrosis of the epithelium from the forestomachs and of the lymphoid tissue of
      the spleen and lymph nodes.

PMID- 10928687
TI  - Respiratory distress secondary to both amphotericin B deoxycholate and lipid
      complex formulation.
AB  - A 73-y-old female with a history of adenocarcinoma of colon and refractory anemia
      developed febrile neutropenia following chemotherapy. Therapy with iv infusion of
      amphotericin B deoxycholate (AmBd) was initiated on day 8 of hospital admission.
      Premedications included acetaminophen, diphenhydramine and meperidine. Patient
      developed rigor, chill and elevated temperature approximately 100 min into the
      infusion. The infusion was temporarily discontinued and rigors subsided following
      administration of 25 mg meperidine im. Infusion was continued after cessation of
      the rigors with no further sequelae. During each infusion of AmBd over the next 3
      d, the patient developed rigor, chill and elevated temperature which was managed
      with meperidine. However, on day 4 she developed respiratory distress,
      bronchospasm and visible cyanosis with oxygen saturation of 88% while on 2 L
      oxygen. The infusion was stopped and the symptoms subsided with administration of
      albuterol via nebulizer. Amphotericin lipid formulation infusion was reinstituted
      after 3 d because of the patient's worsening clinical status. However, the
      patient developed severe respiratory distress approximately 130 min into the
      infusion. The infusion was discontinued and she was treated with albuterol via
      nebulizer. Itraconazole therapy was instituted without any adverse sequelae.
      Clinicians should be aware of this potential adverse event since it can occur
      with all formulation of amphotericin.

PMID- 10928688
TI  - Treatment of atenolol overdose in a patient with renal failure using serial
      hemodialysis and hemoperfusion and associated echocardiographic findings.
AB  - A 28-y-old male with end stage renal failure (ESRF) received an overdose of
      atenolol. Subsequent cardiac arrest and prolonged cardiogenic shock required
      aggressive pharmacologic support, intraaortic balloon pump insertion, and
      mechanical ventilation. Four hemodialyses with charcoal hemoperfusion were
      performed over 72 h. Plasma atenolol levels decreased from 7.4 mg/L to 2.1 mg/L
      although significant rebound occurred between dialyses. Transthoracic
      echocardiogram showed global hypokinesis with an ejection fraction (EF) of 5-10%
      prior to cardiac arrest, compared to baseline and following EF's of approximately
      35%. Our experience supports hemodialysis for ESRF patients with atenolol
      toxicity.

PMID- 10928689
TI  - Pre-school childhood poisoning in Thailand.
AB  - A descriptive study of pre-school poisoning in Khon Kaen province revealed that
      poisoning had a lower incidence rate and a much lower proportion of all hospital
      attendances than that reported in western studies. This could have been because
      grandparents, if not parents, still had a major role in child-rearing. This
      advantage was supported by increased affection as reflected by the finding that
      children were described as easy-to-take-care of ("Jiang-ngai") and not difficult
      ("liang-yaak") children, as reported in previous western studies where non
      related baby-sitters were common. However, many disadvantages including
      illiteracy, age disabilities, improper supervision, and poor understanding of the
      risks of poisoning were identified in child caregivers in this study.

PMID- 10928690
TI  - Multi-center retrospective evaluation of oral benzocaine exposure in children.
AB  - On rare occasions benzocaine has produced methemoglobinemia from oral, rectal and
      dermal exposures. There is disagreement whether this is an idiosyncratic event or
      a dose-related event. To gain a better perspective on this problem we
      retrospectively reviewed cases at 4 large regional poison centers of children <18
      y of age from 1993-1996. One hundred and eighty-eight benzocaine exposures were
      reported. Mean and median ingested dosage were 86.8 (+/- 89.5) mg/kg and 50
      mg/kg, respectively. Fifty-eight patients (30%) were managed in the emergency
      department; 8 patients had methemoglobin levels determined. One child had a
      methemoglobin level of 19%; all others were <1%. One hundred and seventy-three
      patients (92%) remained asymptomatic. Other symptoms were minor: oral numbness
      (8), vomiting (3), and 1 each of oral irritation, dizziness and nausea. In this
      series of accidental ingestions of benzocaine-containing products cyanosis was
      rare and apparently not dose related. These cases may be safely managed at home
      with telephone follow up for at least 2 h. If there is evidence of cyanosis,
      dusky pallor, shortness of breath, or change in mental status direct medical
      evaluation should be recommended.

PMID- 10928691
TI  - Blood lead and cadmium in dogs from urban India.
AB  - Concentrations of lead and cadmium were estimated in blood samples of 43 healthy
      dogs from urban India. Concentrations were 19.5+/-2.1 microg lead/dL and 0.74+/
      0.13 microg cadmium/dL, which were considerably higher for rural dogs. Sex, age,
      and diet had no significant effect on lead and cadmium blood concentrations, yet
      male and adult dogs had higher levels than females and young dogs. The use of
      dogs as sentinels for environment quality in India was indicated by this study.

PMID- 10928692
TI  - One-month parenteral toxicity study of recombinant human basic fibroblast growth
      factor in dogs.
AB  - A 1-mo toxicity study followed by a 1-mo recovery period of recombinant human
      basic fibroblast growth factor (bFGF) was performed using Beagle dogs at doses of
      30, 120 or 480 mg/kg/d to estimate the no observed adverse effect level (NOAEL).
      Subcutaneous thickening was seen and its incidence, as well as that of stiffness
      of the injection sites, increased with dose. There were neither dead animals nor
      significant changes of body weight during the experimental period. In addition,
      no significant bFGF-related changes were found in ophthalmologic and
      histopathological examination, urinalysis and hematological, biochemical and
      organ weight parameters. At necropsy, red-brownish spots and/or nodule formations
      were recognized in a dose-dependent manner. Splenomegaly was noted in the 480
      mg/kg group, but these findings had a low incidence in all dose groups. The
      findings in the dosing period disappeared or were ameliorated during the recovery
      period. The above data suggests the NOAEL of bFGF in Beagle dogs is >480 mg/kg/d.

PMID- 10928694
TI  - Remedies used in Hellenic history.
AB  - A large number of remedies known as "pharmaca" in Greek used for treating a
      disease or for other problems in medical practice have been traced back to the
      Hellenic period of history. Archeological data as well as literary and scientific
      texts suggest that the ancient Greek physicians knew how to use many remedies
      from herbs and plants, metals and minerals, and animals. These remedies were
      given per os, in liquid form (katapotia in Greek), in poultice form, or in the
      form of ointments and eye-drops (collyria). The main problem of ancient
      pharmacology was that chemistry had not yet become a science to help physicians
      individually distinguish each of the substances used as remedies and to estimate
      the exact effect they could cause to the human organism. However, especially
      during the classical period (Sth-4th century BC) and from the end of the Hellenic
      period and thereafter, remedies would be the combinations of substances presented
      clearly and in detail in prescriptions, giving medicine a more scientific profile
      of their workings.

PMID- 10928693
TI  - Effect of thiamine hydrochloride on lead induced lipid peroxidation in rat liver
      and kidney.
AB  - Thiamine hydrochloride was studied on lead-induced endogenous lipid peroxidation
      in rat hepatic and renal tissues following po doses of 2.73 mg lead/kg bw for 6
      w. Simultaneous use of 25 mg thiamine hydrochloride/kg bw po reduced lead
      accumulation in liver and kidneys. There were significant decreases in endogenous
      lipid peroxide in liver and kidney from thiamine hydrochloride-treated rats.
      Histopathological lesions in thiamine-treated livers and kidneys were milder in
      comparison to lesions in untreated Pb-exposed animals. This indicates the
      prophylactic potential of thiamine for lead-induced lipid peroxidation.

PMID- 10928695
TI  - Custer, selenium and swainsonine.
AB  - The Battle of Little Bighorn was fought over 100 y ago but many controversies
      remain. Some feel the defeat of Custer could have been avoided if Benteen and
      Reno had united with Custer. A slow-moving pack train may have hindered the
      troops of Benteen and Reno from joining up with Custer. One report indicated the
      horses and mules in the pack train were lame and behaved crazily. It has been
      previously suggested that the animals had selenium toxicosis. We propose the
      lameness could have been caused by selenium, but that the behavioral problems may
      have been caused by the ingestion of plants containing swainsonine.

PMID- 10928697
TI  - Where are the "roots of toxicology"?

PMID- 10928696
TI  - More on fatal privet toxicosis.

PMID- 10928698
TI  - "Is there a need for blood substitutes in the new millennium and what should we
      expect in the way of safety and efficacy?".

PMID- 10928699
TI  - A novel configuration of bioartificial liver support system based on circulating
      microcarrier culture.
AB  - The purpose of this investigation is to initiate a new bioartificial liver
      support system that utilizes circulating microcarrier cultures in the
      extracapillary space of a hollow fiber cartridge. The material exchange occurs on
      the membranes of the hollow fiber. Toxins are metabolized by the circulating
      cells on the microcarriers driven by a centrifugal pump. We inoculated 2-3 x 10E8
      Hep G2 cells on 2.5 grams of Cytodex 3 microcarriers, and allowed them flowing in
      the extracapillary space of a modified plasma filter. 10% FCS Medium was pumped
      through the capillaries at different rates. Cells keep morphological integrity
      and functionality during the circulation. These preliminary results suggest that
      this configuration of a bioartificial liver support system offers a future
      investigation.

PMID- 10928700
TI  - Cellular volume determination of alginate-entrapped hepatocytes by MRI diffusion
      measurements.
AB  - Cellular volume of hepatocytes entrapped in alginate gel beads were evaluated
      under in vivo conditions in samples having different cell densities by applying
      mathematical models to the diffusion data obtained by magnetic resonance imaging
      (MRI). The calculated average volume is in good agreement with the values from
      the literature-- being closer to the data relative to living tissue than to
      isolated cells. The non invasive characteristics of magnetic resonance imaging
      make this method particularly well suited to obtain information from the intact
      system.

PMID- 10928701
TI  - Adsorption of bilirubin by amine-containing crosslinked chitosan resins.
AB  - Crosslinked chitosan resin, which has good blood compatibility, was prepared by
      crosslinking chitosan solution with glutaraldehyde. Polymeric adsorbents for
      bilirubin have been synthesized by chemical modification of crosslinked chitosan
      resins with di-, tri-, tetra-, and pentammines. The adsorption of bilirubin on
      the adsorbents was investigated in detail. The results indicated that
      electrostatic interaction and hydrophobic interactions are the main driving
      forces for the adsorption. Compared with crosslinked chitosan resin, the
      functionalized chitosan beads have higher adsorption capacity for unconjugated
      and conjugated bilirubin.

PMID- 10928702
TI  - Osteochondral lesion repair of the knee in the rabbit after low-power diode Ga-Al
      As laser biostimulation: an experimental study.
AB  - The purpose of this study was to evaluate whether low-power laser biostimulation
      of the osteo-chondral lesions of the knee could by itself reduce repair healing
      time. Surgery was performed on eighteen rabbits; a bilateral osteo-chondral
      lesion of 2.5mm in diameter and 2mm depth was created in the femoral medial
      condyle with a drill. The left knee of each animal was treated intraoperatively
      using the diode Ga-Al-As laser (780nm) with the following parameters: 300
      Joules/cm2, 1 Watts, 300 Hertz, 10 minutes; the right knee was left untreated, as
      control group. The animals were divided into three groups, A, B and C, according
      to the survival time after surgery, two, six and twelve weeks, respectively. The
      explants from the femoral condyles, either treated employing laser energy or left
      untreated, were examined histomorphometrically. Results after laser treatment
      showed faster healing of the lesion at week 2 (p=0.043) and an overall
      improvement in cellular morphology (p=0.044), while a more regular aspect of the
      osteocartilaginous tissue was observed at week 12 (p=0.004). A relationship
      between laser biostimulation properties and healing of the osteo-chondral defect
      has been demonstrated.

PMID- 10928703
TI  - Xenotransplantation of microencapsulated bovine chromaffin cells into
      hemiparkinsonian monkeys.
AB  - This study examines the effects of xenografts of microencapsulated bovine
      chromaffin cells (BCCs) on the rotational behavior of hemiparkinsonian monkey
      recipients. In addition, it determines the content of monoamine neurotransmitters
      and their major metabolites in the neostriatum in hemiparkinsonian monkeys. The
      hemiparkinsonian model in monkeys was induced by a unilateral intracarotid
      injection of methyl-phenyl-tetrahydropyridine (MPTP). Unencapsulated BCCs, BCCs
      microencapsulated in alginate-polylysine-alginate (ALA) membranes as well as
      empty microencapsules were grafted into the neostriatum of the hemiparkinsonian
      monkeys. Following the transplantation the hemiparkinsonian symptoms subsided and
      the number of rotations induced by apomorphine decreased for up to nine months in
      the group of recipients grafted with microencapsulated BCCs, while only a
      temporary improvement (one month) was detected in the recipients of the
      unencapsulated BCCs. No change was observed in the recipients of empty
      microencapsules. Dopamine and its metabolites were found considerably depleted in
      the MPTP-lesioned side versus the unlesioned side of the neostriatum in the
      hemiparkinsonian monkeys(P<0.05).

PMID- 10928704
TI  - Study on the physiology and degradation of dye with immobilized algae.
AB  - Immobilization of chlorella (pyrenoidosa) with calcium alginate was carried out.
      Both algal growth and physiological activity increased after immobilization.
      Algal size and initial density have little influence on cell growth and
      physiological activity. Algal cell division inside the support was restricted
      without bubbling air containing 2% CO2. Individual algal cell increased and algal
      distribution inside the support was not homogeneous, indicating that within the
      support the resistance of mass transfer of CO2 was the limiting factor for the
      growth and cell division of immobilized algae. After bubbling 2% CO2, algal
      growth, the cell division considerably increased and individual cell size
      restored normally. Study of the degradation of dye (direct brown NM) by
      immobilized algae was better than that of free algae. Bubbling air containing 2%
      CO2 in the culture solution was more favorable for increasing decolorization
      rate. Preliminary study of co-immobilization of algae plus bacterium illustrated
      that the addition of bacterium increased the anabolic activity of algae, thus
      increased the decolorization capacity if immobilized algae for dye.

PMID- 10928705
TI  - Effects of bone marrow cells on hepatocytes: when co-cultured or co-encapsulated
      together.
AB  - Bone marrow cells co-cultured with hepatocytes resulted in hepatocytes that can
      be maintained in culture for 14-21 days. This is compared to 7-10 days with
      hepatocytes alone under the same conditions. Similarly, when bone marrow cells
      are co-encapsulated together with hepatocytes, the viability of hepatocytes in
      culture medium is prolonged to 28 days. This is compared to 14 days when
      hepatocytes are encapsulated alone under the same conditions. These results
      suggest that bone marrow cells can contribute to the viability and maintenance of
      hepatocytes. It addition, this principle could be applied to other situation as
      in helping the regeneration of hepatocytes in liver failure and also for other
      cells and organs.

PMID- 10928706
TI  - Web-based distance continuing education: a new way of thinking for students and
      instructors.
AB  - As people have more difficulty taking time away from work to attend conferences
      and workshops, the idea of offering courses via the Web has become more
      desirable. Addressing a need voiced by Medical Library Association membership,
      the authors developed a Web-based continuing-education course on the subject of
      the librarian's role in evidence-based medicine. The aim of the course was to
      provide medical librarians with a well-constructed, content-rich learning
      experience available to them at their convenience via the Web. This paper
      includes a discussion of the considerations that need to be taken into account
      when developing Web-based courses, the issues that arise when the information
      delivery changes from face-to-face to online, the changing role of the
      instructor, and the pros and cons of offering Web-based versus traditional
      courses. The results of the beta test and future plans for the course are also
      discussed.

PMID- 10928707
TI  - Brandon/Hill selected list of print books and journals in allied health.
AB  - This list of 424 books and 77 journals is intended as a selection guide for print
      literature to be used in a library supporting allied health educational programs
      or allied health personnel in either an academic or health care setting. Because
      of the impossibility of covering the large number and wide variety of allied
      health professions and occupations, the recommended publications are focused
      primarily on the educational programs listed and recognized by the American
      Medical Association and other accrediting bodies. Books and journals are
      categorized by subject; the book list is followed by an author/editor index, and
      the subject list of journals by an alphabetical title listing. Items suggested
      for initial purchase (167 books and 31 journals) are indicated by asterisks. To
      purchase the entire collection of books and journals (2000 subscriptions) would
      require an expenditure of about $31,970. The cost of only the asterisked items
      totals $12,515.

PMID- 10928708
TI  - Standards for vision science libraries. The Association of Vision Science
      Librarians.
AB  - The minimum levels of staffing, services, budget, and technology that should be
      provided by a library specializing in vision science are presented. The scope and
      coverage of the collection is described as well. These standards may be used by
      institutions establishing libraries or by accrediting bodies reviewing existing
      libraries.

PMID- 10928709
TI  - Structuring the pre-search reference interview: a useful technique for handling
      clinical questions.
AB  - OBJECTIVES: To explore whether structuring a literature search request form
      according to an evidence-based medicine (EBM) anatomy elicits more information,
      improves precision of search results, and is acceptable to participating
      librarians. METHODS: Multicenter before-and-after study involved six different
      libraries. Data from 195 minimally structured forms collected over four months
      (Phase 1) were compared with data from 185 EBM-structured forms collected over a
      further four-month period following a brief training intervention (Phase 2).
      Survey of librarians' attitudes toward using the EBM-structured forms was
      conducted early during Phase 2. RESULTS: 380 request forms, EBM-structured and
      minimally structured, were analyzed using SPSS. A statistically significant
      Pearson correlation was found between use of the EBM-structured form and
      complexity of the search strategy (P = 0.002). The correlation between clinical
      requests handled by the EBM-structured form and fewer items retrieved was also
      statistically significant (P = 0.028). However, librarians rated minimally
      structured forms more highly than EBM-structured forms against all dimensions
      except informativeness. CONCLUSIONS: Although use of the EBM-structured forms is
      associated with more precise searches and more detailed search strategies,
      considerable work remains on making these forms acceptable to both librarians and
      users. Nevertheless, with increased familiarity and improved training,
      information retrieval benefits could be translated into more effective search
      practice.

PMID- 10928710
TI  - Expediting the transfer of evidence into practice: building clinical
      partnerships.
AB  - A librarian/clinician partnership was fostered in one hospital through the
      formation of the Evidence-based Practice Committee, with an ulterior goal of
      facilitating the transfer of evidence into practice. The paper will describe
      barriers to evidence-based practice and outline the committee's strategies for
      overcoming these barriers, including the development and promotion of a Web-based
      guide to evidence-based practice specifically designed for clinicians (health
      professionals). Educational strategies for use of the Web-based guide will also
      be addressed. Advantages of this partnership are that the skills of librarians in
      meeting the needs of clinicians are maximized. The evidence-based practice skills
      of clinicians are honed and librarians make a valuable contribution to the
      knowledge-base of the clinical staff. The knowledge acquired through the
      partnership by both clinicians and librarians will increase the sophistication of
      the dialogue between the two groups and in turn will expedite the transfer of
      evidence into practice.

PMID- 10928711
TI  - Positive image and high profile gets results in a hospital library.

PMID- 10928712
TI  - Interlibrary loan availability of nursing journals through DOCLINE and OCLC: a
      five-state survey.

PMID- 10928713
TI  - Library requirements and problem-based learning: The Medical Sciences Library,
      The University of the West Indies.

PMID- 10928714
TI  - Medical Subject Headings (MeSH).

PMID- 10928715
TI  - SERHOLD and the public's access to health information.

PMID- 10928716
TI  - Marking retracted papers at The Webster Pendergrass Agriculture Veterinary
      Medicine Library.

PMID- 10928717
TI  - J. Michael Homan, Medical Library Association President, 2000-2001.

PMID- 10928718
TI  - A psychopharmacological study of the relationship between brain catalase activity
      and ethanol-induced locomotor activity in mice.
AB  - OBJECTIVE: The present experiments analyze the effects of the brain catalase
      inhibitor 3-amino-1,2,4-triazole (AT) on the locomotor activity induced by
      ethanol. METHOD: In the first experiment, mice received injections of either AT
      (0.5 g/kg) or saline (S) 5 hours prior to an ethanol injection (0, 0.8, 1.6, 2.4,
      3.2 or 4 g/kg). In the second experiment, five different groups of mice received
      injections of AT (0, 0.010, 0.030, 0.060, 0.125, 0.250 or 0.500 g/kg) 5 hours
      prior to being injected with 1.6 g/kg of ethanol. In the third experiment, six
      groups of mice were treated with AT (0.5 g/kg), simultaneously, 2.5, 5, 10 or 20
      hours before the administration of 1.6 g/kg of ethanol. Immediately after ethanol
      injection, mice were placed individually in the open-field apparatus for 20
      minutes. In another set of experiments, the effects of AT on brain catalase
      activity were studied. Animals were injected with AT at 0, 0.010, 0.030, 0.060,
      0.125, 0.250 or 0.500 g/kg, and 5, 10 or 20 hours following AT treatment mice
      were perfused and the brain was removed. RESULTS: Pretreating mice with AT
      reduces ethanol-induced locomotor activity (1.6, 2.4 and 3.2 g/kg) without
      altering spontaneous locomotion. Pretreatment with AT (from 0.125 g/kg to 0.5
      g/kg) produced a clear dose-dependent decrease of ethanol locomotion and brain
      catalase activity. The effect of AT was observed 5 and 10 hours after the
      injection of this drug, and it disappeared 20 hours following AT treatment.
      CONCLUSIONS: Current data showed a parallel property of AT in producing a
      remarkable dose- and time-dependent decrease in catalase activity and ethanol
      locomotion.

PMID- 10928719
TI  - The direct and indirect relationships between alcohol prevention measures and
      alcoholic liver cirrhosis mortality.
AB  - OBJECTIVE: The objective of this article is to investigate direct and indirect
      relationships between prevention measures and alcoholic liver cirrhosis mortality
      in Canadian provinces from 1968 to 1986. METHOD: The data base that was assembled
      included alcoholic cirrhosis mortality rates, alcohol availability measures (rate
      of licensed premises, year in which the legal drinking age was reduced), per
      capita consumption of alcohol, rates of AA members and groups, and economic and
      demographic measures. This article develops a two-equation analytic model based
      on the availability theory of alcohol problems and prevention (Single, 1988). The
      distinction between direct and indirect effects of prevention measures can be
      made explicitly with this model. RESULTS: Alcohol availability measures, but not
      AA measures, had a significant direct potential impact on alcohol consumption. AA
      measures had a significant direct relationship to cirrhosis mortality rates.
      Alcohol consumption also had a significant direct relationship to cirrhosis
      mortality, and alcohol availability measures had an important indirect
      relationship through their influence on per capita alcohol consumption.
      CONCLUSIONS: While these observations need to be interpreted cautiously, the two
      equation model shows promise as an approach to understanding direct and indirect
      influences on alcohol problems. As expected, AA measures and per capita alcohol
      consumption demonstrated significant direct relationship to cirrhosis mortality.
      In addition, important indirect influences of drinking-age changes and rates of
      licensed premises on cirrhosis mortality were observed through their
      relationships to per capita alcohol consumption.

PMID- 10928720
TI  - Alcohol and unnatural deaths in Sweden: a medico-legal autopsy study.
AB  - OBJECTIVE: To investigate alcohol involvement in all types of unnatural deaths in
      Sweden. METHOD: All cases of unnatural death that underwent medico-legal
      autopsies (1992-1996) in Sweden were analyzed (N = 15,630; i.e., 68% of all
      unnatural deaths). Alcohol was regarded as contributing to the death if: (1)
      there was any indication that the deceased was a "known alcoholic"; (2) the
      underlying or contributing causes of death were alcohol-related; (3) the deceased
      had alcohol-related inpatient diagnosis during a period of 3 years prior to
      death; or (4) the case tested positive for blood alcohol. RESULTS: Thirty-nine
      percent of the blood-tested cases (n = 13,099) were positive for alcohol. Almost
      40% of the unnatural deaths were associated with alcohol. Alcohol involvement was
      most common in the intoxication group (84%), followed by the "undetermined"
      (65%), homicide (55%), fall (48%), fire (44%), asphyxia (41%), suicide (35%) and
      traffic (22%) groups. More than half (52%) of the deaths in the age group 30-60
      years, 35% of those aged 0-29 years and 25% of those aged 60 and over were
      associated with alcohol. CONCLUSIONS: In Sweden, two of five unnatural deaths are
      associated with alcohol; this is a conservative estimate. Alcohol-associated
      mortality varies considerably between different groups of external causes of
      death, between men and women, and with age.

PMID- 10928721
TI  - Drinking and driving: explaining beverage-specific risks.
AB  - OBJECTIVE: This study tested whether the association of beer drinking with
      drinking and driving is due to cultural norms or is an artifact arising from the
      demographic profile of beer drinkers (young and male), the drinking patterns of
      this subpopulation (frequent and heavy), and the venues in which they prefer to
      drink (bars and restaurants). METHOD: Telephone survey data from six U.S.
      communities were used to establish the demographic characteristics of drinkers,
      their consumption patterns, beverage preferences, preferred drinking venues and
      self-reported drinking and driving rates. The survey completion rate was 64.6%. A
      total sample of 5,231 drinkers was divided into test and validity samples. After
      deletion of cases with missing data, the test sample included 2,275 drinkers, of
      whom 985 had driven after drinking. RESULTS: Controlling for a broad set of
      covariates, the analyses showed that frequent consumers were more likely to drink
      outside the home, preferred beer and spirits to wine, and were more likely than
      others to drink and drive. Beverage preferences were not directly associated with
      drinking and driving. Beer drinkers, however, were from the subpopulation most
      likely to drink and drive: heavier drinking younger men, who prefer to drink at
      bars and restaurants. CONCLUSIONS: These results suggest that the association of
      beer consumption with drinking-driving arises from the circumstances in which the
      subpopulation of beer drinkers more commonly find themselves (as a result of
      their efforts to maximize, within economic constraints, the social and amenity
      value of drinking), as opposed to any culturally induced disposition beer
      drinkers may have to drink and drive.

PMID- 10928722
TI  - Adolescent and young adult antisocial behavior and adult alcohol use disorders: a
      fourteen-year prospective follow-up in a national survey.
AB  - OBJECTIVE: Data from the National Longitudinal Survey of Youth (NLSY) are used to
      examine the association between antisocial behaviors (ASB) reported in youth (15
      22 years old) and alcohol use disorders (AUD) 14 years later in a large (N =
      7,326) representative national sample. METHOD: Structural equation modeling
      generalized to dichotomous outcomes was used to assess the associations between
      latent variables of ASB with latent variables of AUD and background variables.
      RESULTS: Exploratory factor analysis of 17 ASB items yielded three factors having
      clear interpretations with the literature-property offenses, person offenses and
      illicit substance involvement. When examined in the context of the multivariate
      structural equation model, several independent associations between ASB and AUD
      symptoms and covariates were found. Although there were significant and
      independent effects for each ASB factor on each of the alcohol use disorder
      factors, the strength of the association was strongest for the effects of early
      illicit substance involvement on alcohol abuse and dependence. CONCLUSIONS: Both
      illicit substance involvement and delinquency other than illicit substance
      involvement reported in 1980 were associated with alcohol use disorders 14 years
      later.

PMID- 10928723
TI  - Long-term outcomes of alcohol use disorders: comparing untreated individuals with
      those in alcoholics anonymous and formal treatment.
AB  - OBJECTIVE: The aim of this study was to examine how the type and timing of help
      received over 8 years by previously untreated problem drinking individuals were
      linked to drinking and functioning outcomes. METHOD: At the time of the 8-year
      follow-up, individuals (N= 466, 51% male) had self-selected into four groups: no
      treatment (n = 78), Alcoholics Anonymous (AA) only (n = 66), formal treatment
      only (n = 74), or formal treatment plus AA (n = 248). RESULTS: Individuals who
      received some type of help--AA, formal treatment or both--were more likely to be
      abstinent at 8 years than were untreated individuals. Although the AA only group
      was better off than the formal treatment only group at 1 and 3 years, the
      informally and formally treated groups were equivalent on drinking outcomes at 8
      years. Similarly, despite the formal treatment plus AA group having been better
      off at 1 and 3 years than the formal treatment only group, the two formal
      treatment groups were comparable on drinking at 8 years. Both helped and
      untreated individuals improved between baseline and 1 year on drinking outcomes,
      but only formally treated individuals showed continued improvement over 8 years
      on drinking indices. Participation in AA or formal treatment during Year 1 of
      follow-up was associated with better drinking outcomes at 8 years. CONCLUSIONS:
      Individuals who obtain help for a drinking problem, especially relatively
      quickly, do somewhat better on drinking outcomes over 8 years than those who do
      not receive help, but there is little difference between types of help on long
      term drinking outcomes.

PMID- 10928724
TI  - Characteristics of American-Indian clients seeking inpatient treatment for
      substance abuse.
AB  - OBJECTIVE: The current study was conducted as a preliminary examination of
      substance use and some of its correlates in nonreservation-residing American
      Indians. METHOD: A group of 522 American-Indian (AI) subjects (473 men) were
      compared with two sets of geographic controls: (1) an equal number of African
      Americans (AA) and (2) an equal number of European Americans (EA). All received
      treatment in the same facilities over the same time period. RESULTS: Contrary to
      expectations, the ethnic/racial groups were remarkably similar on a number of
      alcohol use variables, including the amount consumed in the 6 months prior to
      treatment and the number of previous treatments. Among those self-reporting as
      problem drinkers, there were group differences in the age of first drink (AA mean
      = 13.54, AI mean = 12.24 and EA mean = 11.71) and first drunk (AA mean = 15.80,
      AI mean = 14.23 and EA mean = 14.08) and the number of alcohol-related problems
      (AA mean = 7.52, AI mean = 8.49 and EA mean = 8.46). On these measures, AI and EA
      subjects did not differ whereas AA subjects reported a later age of onset and
      fewer negative consequences. EA and AI male subjects reported marijuana as their
      most frequently used "other" drug, whereas AA male subjects listed stimulants as
      their primary drugs. Regardless of ethnic/racial group, women did not differ on
      their drug(s) of choice, reporting stimulants as the most frequently abused drug
      (after accounting for alcohol use). CONCLUSIONS: This preliminary study is
      remarkable for the observed similarities among groups. Future studies using more
      rigorous sampling are needed to provide clarification of this preliminary study.

PMID- 10928725
TI  - Factors affecting motivation to treatment in severely dependent alcoholics.
AB  - OBJECTIVE: This article explores environmental, developmental and personality
      related factors as predictors of motivation to treatment for alcoholism, using
      such concepts as: social situation on admission, treatment career, age, education
      and adventurous patterns of behavior. METHOD: The original population consists of
      603 severely dependent alcoholic patients (76% men, 42% compulsorily committed)
      with a mean age of 40 years. In structural equation model estimation, 85% of the
      original cases were used (N = 511), made up of compulsorily as well as
      voluntarily admitted patients. A reduced model was tried on voluntary patients
      alone. RESULTS: In the main model, patterns of behavior and age were not related
      to the motivation to treatment, while treatment career had some negative impact.
      Social problems were related to less motivation to treatment. In turn, a worse
      social situation was related to more treatment experience. The reduced model on
      voluntary patients alone confirmed the main findings, although more previous
      treatment tended to be related to more motivation. CONCLUSIONS: Motivation was
      mostly related to a better social situation (i.e., having "more to lose"). A
      collapse in the social situation was more of an obstacle than a promoter of
      motivation. There was no support for statements that "maturing out" would result
      in more motivation, and findings were inconclusive concerning the impact on
      motivation of having had many previous treatment experiences. The pattern of
      behavior was not directly related to the level of motivation. Based on these
      findings, the relevance of social work for motivation to treatment is discussed.

PMID- 10928726
TI  - A randomized controlled trial of Moderation-Oriented Cue Exposure.
AB  - OBJECTIVE: A randomized controlled trial was conducted to examine the
      effectiveness of Moderation-Oriented Cue Exposure (MOCE) in comparison to
      Behavioral Self-Control Training (BSCT). The main hypothesis was that MOCE would
      be more effective than BSCT among a sample of problem drinkers aiming at moderate
      drinking. A subsidiary hypothesis was that MOCE would be relatively more
      effective than BSCT among problem drinkers with higher levels of alcohol
      dependence. METHOD: Clients (N = 91; 75% men) were randomly allocated to either
      MOCE or BSCT. Treatment was delivered in weekly sessions by two trained
      therapists, in a nested design in which therapists switched to the alternative
      treatment modality approximately halfway through the trial. Follow-up was carried
      out 6 months following posttreatment assessment, with 85% successful contact.
      RESULTS: There was no evidence for the general superiority of MOCE over BSCT. The
      subsidiary hypothesis was not confirmed. A subsample of clients (n = 14) showing
      levels of dependence at baseline above the commonly accepted cut-point for a
      moderation goal (Severity of Alcohol Dependence Questionnaire [SADQ] > 29) showed
      outcomes at least as favorable as those below the cut-point. The validity of self
      reports of alcohol consumption and problems was supported by significant
      relationships with liver function tests (gamma-glutamyl transferase and alanine
      transferase). CONCLUSIONS: These results provide no grounds for the replacement
      of BSCT by MOCE in routine, moderation-oriented treatment practice. Assuming they
      prefer it to abstinence and that it is not contra-indicated on other grounds,
      there seems no reason why clients showing a higher level of dependence (SADQ = 30
      45) should not be offered a moderation goal.

PMID- 10928727
TI  - Alcohol affects processing of ignored stimuli in a negative priming paradigm.
AB  - OBJECTIVE: This research examined the effect of alcohol on negative priming,
      which is considered to reflect a basic process of selective attention. METHOD:
      Male social drinkers (N = 28) performed a color naming reaction time (RT) task
      that measured negative priming. After a baseline test on the task, they received
      either 0.56 g/kg of alcohol or a placebo; they then performed the task twice.
      RESULTS: In accord with the hypotheses, alcohol suppressed negative priming
      during the ascending limb but not during the descending limb of the blood alcohol
      curve. No suppression of negative priming was evident under placebo. CONCLUSIONS:
      The suppression of this process by alcohol may represent a basic mechanism by
      which the drug reduces the ability to efficiently allocate attention and leads to
      impaired performance on various attention-based tasks (e.g., divided attention
      and vigilance tasks).

PMID- 10928728
TI  - Screening adolescents for problem drinking: performance of brief screens against
      DSM-IV alcohol diagnoses.
AB  - OBJECTIVE: The performance of three brief screens, the CAGE, TWEAK and Alcohol
      Use Disorders Identification Test (AUDIT), was evaluated against a DSM-IV
      diagnosis of alcohol abuse or dependence in an adolescent sample. METHOD:
      Adolescents (13-19 years old) who presented to an emergency department for
      treatment of an injury, and who tested negative for blood alcohol concentration
      at time of admission, were administered a structured diagnostic interview and
      modified versions of the CAGE, TWEAK and AUDIT. RESULTS: Of the 415 adolescents
      for whom complete data were available, 18% met criteria for a DSM-IV alcohol use
      disorder according to the Diagnostic Interview Schedule for Children (version
      2.3). Teens who reported alcohol use in the last year (n = 261, 58% male, 71%
      white) were included in analyses that compared the performance of the three
      screening instruments. Receiver Operating Characteristic analysis indicated that
      the AUDIT demonstrated the best performance across the range of its cut-scores,
      with optimal performance at a cut-score of 4. The TWEAK performed optimally at a
      cut-score of 2 and the CAGE at a cut-score of 1. CONCLUSIONS: Routine alcohol
      screening among adolescents seen in a hospital setting is indicated. Two
      important directions for future research include the identification of adolescent
      specific alcohol screening items, and the validation of an adolescent-specific
      definition of problem drinking that addresses limitations of DSM-IV alcohol
      diagnoses when applied to adolescents.

PMID- 10928729
TI  - Adolescent individuation and alcohol use in multi-ethnic youth.
AB  - OBJECTIVE: A structural equation modeling approach is used to assess adolescent
      alcohol use as a function of two measures of individuation in the context of
      other family and peer psychosocial factors for adolescents in three ethnic
      groups. The separation measure captures aspects of individuation related to
      detachment or rebelliousness. Intergenerational individuation measures increasing
      self-reliance and control with maintenance of supportive family bonds. METHOD: A
      sample of 1,200 sixth through eighth grade black, Mexican-American and non
      Hispanic white adolescents participated. A structural equation model describing
      adolescent alcohol use as a function of two measures of individuation, family
      conflict, communication with mother, stress and peer use of alcohol was tested
      and compared for the three ethnic groups. RESULTS: Significant direct and
      indirect paths to adolescent alcohol use were indicated for individuation
      measures and family use, peer use and stress variables. The proposed model fit
      for each of the groups, although the way in which separation related to stress
      was different in the black group. CONCLUSIONS: The findings support the role of
      individuation as a contributing factor in adolescent alcohol use for each ethnic
      group. They indicate the importance of family and parent-adolescent relationships
      in adolescent alcohol use and suggest directions for both family-based and school
      based preventive interventions.

PMID- 10928730
TI  - College student drinking: an examination of theoretical models of drinking
      tendencies in freshmen and upperclassmen.
AB  - OBJECTIVE: The present research contrasted theoretical models of college student
      drinking tendencies (normative, social control, maturing out). METHOD: Three
      groups of students (N = 364; 62. 1% female) from a moderately sized northwestern
      university were examined: traditional freshmen, nontraditional freshmen and
      upperclassmen. Participants completed measures assessing drinking tendencies,
      drinking consequences and drinking beliefs. RESULTS: Support for a given
      theoretical model was dependent upon which outcome variables were being examined
      (e.g., drinking tendencies vs drinking consequences). Nontraditional freshmen
      were similar to their traditional freshmen counterparts in the amount of alcohol
      they consumed but were more like upperclassmen in the experience of consequences
      of drinking alcohol. Examination of drinking beliefs yielded inconsistent model
      support. CONCLUSIONS: It appears that different types of college students drink
      for different reasons, suggesting a "one size fits all" intervention is less
      likely to be effective. The findings are discussed with respect to different
      interventions for changing drinking tendencies, drinking consequences and
      drinking beliefs, and the timing of those interventions.

PMID- 10928731
TI  - Psychosocial and behavioral factors in early adolescence as predictors of heavy
      drinking among high school seniors.
AB  - OBJECTIVE: Most adolescents experiment with alcohol, and the use of alcohol
      typically escalates during the teenage years. The present study examined how
      several risk and protective factors measured during early adolescence were
      associated with heavy drinking in a sample of high school seniors. METHOD: As
      part of a school-based survey, seventh-grade students (N = 1,132) reported
      degrees of experimentation with alcohol and cigarettes. Several psychosocial
      factors deemed to be important in the etiology of drinking were also assessed.
      Students were followed-up in the twelfth grade, when 16% were categorized as
      heavy drinkers based on drinking and drunkenness frequency and quantity typically
      consumed. RESULTS: Logistic regression analyses revealed that heavy drinking was
      predicted by having had experimented with alcohol or cigarettes, having had a
      majority of one's friends drink and having had poor behavioral self-control in
      early adolescence. In addition, several effects were limited to either boys or
      girls. For example, positive alcohol expectancies predicted greater later heavy
      drinking in boys, while friends' smoking predicted later heavy drinking in girls.
      CONCLUSIONS: The findings suggest that early intervention programs aimed at
      preventing alcohol use by addressing the social and psychological determinants of
      alcohol use may have important preventive effects in terms of later heavy
      drinking.

PMID- 10928732
TI  - Early identification of risk for effects of prenatal alcohol exposure.
AB  - OBJECTIVE: Fetal alcohol syndrome (FAS) and less severe outcomes are typically
      diagnosed later in childhood, although earlier diagnosis of the effects of
      exposure would allow intervention in infancy and prevention of associated
      secondary disabilities. Identification is particularly difficult in such high
      risk groups as low-birthweight infants. The goal of this study was to develop
      methods for early identification of at-risk infants. METHOD: Three methods
      (microcephaly, heavy episodic drinking [> 5 drinks/occasion] in pregnancy and a
      cumulative risk index) identified neonates at risk for those developmental
      consequences of prenatal exposure that can be measured at 6 and 12 months (i.e.,
      standard scores on Bayley Scales of Infant Development and growth measures). The
      usefulness of these methods was assessed by comparing those infants selected to
      an unexposed contrast group, while controlling for potentially confounding
      factors (e.g., race, socioeconomic status and birthweight). RESULTS: At 6 months,
      when 70 infants were tested, trends were found for lower language facet scores
      and lower scores on the Behavioral Regulation Scale; at 12 months, when 134 were
      tested, alcohol-exposed infants had significantly lower cognitive facet scores (p
      < .02) and were more likely to be classified as either mildly or significantly
      developmentally delayed (p < .02). CONCLUSIONS: It is possible to identify
      infants at risk for alcohol-related developmental delays using information
      available in the neonatal period, although it is not usually done. Of the three
      methods tested, a cumulative risk index based on maternal characteristics was
      found to be most predictive.

PMID- 10928733
TI  - The effect of screening on prevalence estimates of alcohol dependence and social
      consequences.
AB  - OBJECTIVE: Screener items are often used in surveys to identify individuals who
      are at high risk of experiencing alcohol dependence or alcohol-related problems.
      The purpose of this study is to determine the effect of two screener items (5 or
      more drinks ever and > or = 12 drinks last year) on prevalence estimates of
      alcohol dependence and negative social consequences. METHOD: The 1995 National
      Alcohol Survey data were analyzed. Differences in prevalence estimates between
      the unscreened current drinkers (n = 2,817) and the two screened samples: 5+ ever
      (n = 2,186) and > or = 12 drinks last year (n = 2,126) were compared. For each
      screened sample, prevalence estimates obtained from two base populations
      (screened positives only and all current drinkers assuming no alcohol-related
      problems among screened negatives) were examined. RESULTS: Comparisons of
      prevalence estimates of alcohol dependence and negative social consequences
      across the screened and unscreened samples revealed little bias in estimates with
      one exception. The only significant difference between the unscreened and
      screened samples was found among women when prevalence rates were obtained from
      data of screened positive respondents only. CONCLUSIONS: The effect of screening
      on national prevalence estimates of alcohol dependence and social consequences is
      small. Less bias in prevalence estimates is found when negatively screened light
      drinkers were assumed to report no alcohol-related problems rather than excluded
      from the estimation sample.

PMID- 10928734
TI  - Do changes in per capita consumption mirror changes in drinking patterns?
AB  - OBJECTIVE: The goal of this study was to examine how well per capita alcohol
      consumption figures derived from beverage sales data relate to changes over time
      in survey-based measures of drinking patterns. It was expected that strong
      associations would be found among these various measures of consumption. METHOD:
      Data from 12 household surveys conducted in Ontario between 1977 and 1997
      provided information on: percentages of drinkers; daily drinkers; those drinking
      five or more drinks at a sitting weekly; those reporting two or more alcohol
      related harms; and average number of drinks per week. These variables were then
      correlated with per capita consumption. RESULTS: Significant correlations were
      found only between per capita consumption and percentage of daily drinkers, and
      between percentage of drinkers and average number of drinks per week.
      CONCLUSIONS: The relationship of per capita consumption to survey measures of
      drinking is weak. The absence of consistent associations over time between per
      capita consumption and survey measures may be attributable to the small number of
      available data points or to increases in unrecorded consumption. Further research
      is needed to verify and explain these results.

PMID- 10928735
TI  - Alcohol-related aggression in the general population.
AB  - OBJECTIVE: This study estimates the relationships between drinking in the event
      and drinking patterns and different levels of aggression severity. METHOD: A
      telephone survey of 1,001 adults (542 women) age 18 and over was conducted
      (response rate of 67%) using computer assisted telephone interviewing (CATI).
      Respondents were asked whether they had been personally involved in a serious
      argument, an incident involving threat, or physical aggression in the past year
      and whether anyone had been drinking alcohol in the most recent incident.
      Respondents also reported their typical alcohol consumption patterns. RESULTS:
      The proportion of respondents reporting involvement in serious arguments, threats
      or physical aggression was 19.8%, 11.8% and 12.0%, respectively. Someone in the
      incident had been drinking in 38.1% of serious arguments, 56.5% of threats and
      67.9% of incidents of physical aggression. When gender, age, education, marital
      status and employment status were controlled for, high quantity drinking (as
      measured by the largest number of drinks consumed on one drinking occasion in the
      past year), overall estimated annual volume of alcohol consumed, and frequency of
      consuming five drinks per occasion were significantly greater for physical
      aggression, compared with arguments and no aggression. However, drinker status
      (abstainer/drinker) and frequency of drinking were not significantly associated
      with involvement in aggression. In a logistic regression analysis controlling for
      demographic variables, a composite measure of alcohol consumption was highly
      significant for physical aggression versus no aggression and for physical versus
      verbal aggression. Physical aggression was also associated with being younger,
      separated/ divorced and a student. CONCLUSIONS: The results suggest that alcohol
      intoxication, rather than mere alcohol consumption, is associated with
      aggression. Moreover, alcohol intoxication is more strongly associated with
      physical aggression than with verbal aggression.

PMID- 10928736
TI  - Conceptual and perceptual implicit memory in Huntington's disease.
AB  - The aims of this study were to examine and compare perceptual and conceptual
      implicit memory (CIM) in Huntington's disease (HD) and to characterize the
      relationship between tests of frontal lobe functioning and CIM. Sixteen HD
      patients and 16 normal controls completed structurally parallel tests of
      perceptual implicit memory and CIM (i.e., rhyme and category exemplar
      generation), tests of explicit memory, and verbal fluency. HD patients showed
      intact implicit memory for both rhyme and category exemplars, despite evidence of
      frontal dysfunction on other tests. An unexpected finding was that patients
      showed a deficit in cued rhyme generation that correlated with severity of
      neurological impairment. The authors replicated findings in controls of a
      correlation between letter fluency and CIM but found no relationship in patients.
      Frontal dysfunction in HD may lessen the influence of generative strategies on
      tests of CIM without compromising performance.

PMID- 10928737
TI  - Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome:
      relation to ataxia.
AB  - The authors used magnetic resonance imaging to measure gray and white matter
      volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC)
      men aged 23-72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1
      woman with alcoholic Korsakoff s syndrome (KS). NC and ALC took quantitative gait
      and balance tests. Gray but not white matter volume declined with normal age in
      both hemispheres and anterior-superior vermis. ALC had gray but not white matter
      cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue
      types. ALC and KS had gray and white matter volume deficits in anterior superior
      but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly
      and selectively correlated with white matter volume in anterior superior vermis.
      Regional distribution but not severity of cerebellar volume deficits is similar
      in alcoholic individuals whether or not complicated by KS and relates to ataxia.

PMID- 10928738
TI  - A comparison of rCBF patterns during letter and semantic fluency.
AB  - To evaluate the functional neuroanatomies underlying letter and category fluency,
      18 normal controls were studied with oxygen-15 water regional cerebral blood flow
      positron emission tomography. Three counterbalanced conditions each consisted of
      6 trials (45 s each): letter fluency (generating words when cued with a
      particular letter), semantic fluency (generating words when cued with a
      particular category), and a control condition (generating days of the week and
      months of the year). Relative to the control, participants activated similar
      brain regions during both fluency tasks, including the anterior cingulate, left
      prefrontal regions, thalamus, and cerebellum; reductions were found in parietal
      and temporal regions. In a direct comparison of the 2 fluency tasks, inferior
      frontal cortex and temporoparietal cortex (hypothesized to participate in a
      phonologic loop for accessing word pronunciation) were activated more during
      letter than semantic fluency, whereas left temporal cortex (associated with
      access to semantic storage) was activated more during semantic than letter
      fluency. This study identifies subtle differences in the neural networks
      underlying letter and semantic fluency that may underlie the dissociation of
      these abilities in patients.

PMID- 10928739
TI  - Functional magnetic resonance imaging evidence for right-hemisphere involvement
      in processing unusual semantic relationships.
AB  - Brain areas active in generating usual (typical) or unusual (atypical) noun-verb
      relations were examined using functional magnetic resonance imaging. Seven adults
      generated the 1st verb to come to mind (usual verb) in response to novel and
      repeated nouns (priming test) and then generated either an unusual verb or the
      1st verb to come to mind in response to novel nouns (unusual test). The left
      inferior prefrontal cortex (LIPC) and right cerebellum were more active when
      generating usual verbs to novel nouns than to repeated nouns. When participants
      generated unusual verbs, there was no increased activation in LIPC, but there was
      increased activity in the right middle and superior frontal gyri, left middle
      frontal gyrus, and bilateral cerebellum. Results support theories that the right
      hemisphere is involved in the processing of distant associations that may be
      useful in creative thought and problem solving.

PMID- 10928740
TI  - Cerebral lateralization and cognitive functioning in patients with congenital
      adrenal hyperplasia.
AB  - A battery of tests was administered to 17 patients with congenital adrenal
      hyperplasia (CAH) and 17 normal controls to investigate the effect of prenatal
      androgen exposure on cerebral lateralization and cognitive performance.
      Individuals were compared on measures of hand preference, verbal and performance
      IQ, and temporal processing asymmetry. A higher incidence of left-handedness was
      found among CAH participants. CAH individuals exhibited higher performance IQs as
      opposed to verbal IQs. Temporal processing asymmetries were investigated using an
      auditory gap detection task. Measures of reaction time and response error
      revealed a right-ear, therefore left-hemisphere, advantage for gap detection.
      This right-ear advantage did not differ between CAH individuals and controls.
      Results partially support the hypothesis that prenatal androgen exposure causes a
      shift in cerebral lateralization toward right-hemisphere dominance.

PMID- 10928741
TI  - Processing lexical ambiguities in word triplets: evidence of lexical-semantic
      deficits following dominant nonthalamic subcortical lesions.
AB  - Lexical-semantic function was investigated in 10 participants with lesions of the
      dominant nonthalamic subcortical (NS) region and a matched normal control group.
      Participants performed speeded lexical decisions on the 3rd member of auditorily
      presented word triplets. The 4 critical triplet conditions were concordant (coin
      bank-money), discordant (river-bank-money), neutral (day-bank-money), and
      unrelated (river-day-money). When the interstimulus interval (ISI) between the
      words in the triplets was 100 ms, patients with NS lesions obtained priming that
      indicated nonselective lexical access; at 1,250-ms ISI, however, there was no
      significant priming effect. This pattern of results is consistent with the view
      that patients with NS lesions can automatically access lexical-semantic
      information but may be unable to sustain lexical activation through controlled or
      attentional forms of processing.

PMID- 10928742
TI  - Implicit memory for music in Alzheimer's disease.
AB  - Short, unfamiliar melodies were presented to young and older adults and to
      Alzheimer's disease (AD) patients in an implicit and an explicit memory task. The
      explicit task was yes-no recognition, and the implicit task was pleasantness
      ratings, in which memory was shown by higher ratings for old versus new melodies
      (the mere exposure effect). Young adults showed retention of the melodies in both
      tasks. Older adults showed little explicit memory but did show the mere exposure
      effect. The AD patients showed neither. The authors considered and rejected
      several artifactual reasons for this null effect in the context of the many
      studies that have shown implicit memory among AD patients. As the previous
      studies have almost always used the visual modality for presentation, they
      speculate that auditory presentation, especially of nonverbal material, may be
      compromised in AD because of neural degeneration in auditory areas in the
      temporal lobes.

PMID- 10928743
TI  - Alterations of visual search strategy in Alzheimer's disease and aging.
AB  - Visual search, characterized by eye fixation patterns, was examined in 8 patients
      with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and
      8 young control participants as they searched for a number among a nonlinear
      array of letters on a large computer screen. Among the 3 groups, target detection
      accuracy differed and detection time increased linearly. There were more
      fixations, and fixation duration was significantly longer in the AD patients than
      in the other 2 groups. These factors contributed to the lengthening of target
      detection time. This qualitative difference in the architecture of visual search
      between AD and aging may reflect a specific deficit in the disengagement of
      visual spatial attention, a prolongation of saccade initiation, or inefficiency
      in planning a search strategy.

PMID- 10928744
TI  - Age effects on executive ability.
AB  - Heterogeneity of executive tasks has made it difficult to determine whether there
      are age-related declines in executive functioning. To address this issue, 112
      individuals, 20-79 years old, took the California Trail Making Test (CTMT) and
      the California Stroop Test (CST), subtests of the Delis-Kaplan Executive Function
      Scale (D. C. Delis, E. Kaplan, & J. H. Kramer, in press) that include measurement
      of component skills embedded in the executive function tasks. Multiple regression
      analyses revealed that after controlling for component skills, age had a
      significant effect on the executive requirement of the CST, namely speed on the
      interference condition. Age did not affect switching performance on the letter
      number condition of the CTMT. Additional analyses revealed that age was
      significantly associated with commission of certain types of errors. This study
      confirms the importance of partialing out components in the assessment of
      multidimensional cognitive tasks, particularly when making age comparisons. It
      also emphasizes specificity over generalizability when examining the impact of
      age on cognition.

PMID- 10928745
TI  - Visuoconstructional problems in dementia: contribution of executive systems
      functions.
AB  - Visuoconstructional ability was assessed by asking patients diagnosed with
      Alzheimer's disease (AD), ischaemic vascular dementia (IVD), and Parkinson's
      disease (PD) and a normal control group (NC) to copy a modification of the Rey
      Osterrieth Complex Figure (M-ROCF). The drawings of the NC group were superior to
      all dementia participants. AD patients generally outperformed IVD and PD
      patients; however, there were few differences between IVD and PD groups.
      Nonetheless, the drawings of IVD and PD patients were very fragmented and
      contained numerous perseverations and omissions. Despite these errors, patients
      with IVD and PD obtained higher delayed recognition memory scores than AD
      patients. Correlational analyses among dementia patients between
      neuropsychological tests and the copy of the M-ROCF found that accurate figure
      copy was most consistently correlated with tests of working memory, that is,
      tests requiring patients to monitor their behavior and sustain a complex mental
      set while performing mental manipulations. By contrast, no relationship between
      executive function tests related to measures of response selection/inhibition or
      other domains of neuropsychological functioning was found.

PMID- 10928746
TI  - Acquisition and transfer of new verbal information in amnesia: retrieval and
      neuroanatomical constraints.
AB  - Four experiments examined new associative learning in amnesia by contrasting the
      performance of 2 amnesic participants-1 (C.C.) with basal forebrain damage and
      the other (R.H.) with medial temporal lobe damage--and 3 controls. Both amnesic
      individuals were severely impaired on explicit memory measures but showed intact
      perceptual priming. On the new associations measures, only C.C., not R.H.,
      exhibited learning by producing correct targets (HIJACKER) in the absence of
      perceptual cues for them (e.g., STAFF shot ???). When the perceptual cue (e.g.,
      MEDICINE cured _I_C_P) was provided, both C.C. and R.H. showed learning. Transfer
      to information containing conceptually related targets (e.g., TERRORIST or BELCH)
      was reliably observed only in C.C. This finding was replicated with further
      reduction in perceptual overlap across original (LIGHTNING torched JUNGLE) and
      transfer (LIGHTNING burned WILDERNESS) sentences. Together, these findings
      delineate the role of experimental conditions, severity of amnesia, and different
      neuroanatomical structures in mediating new verbal learning in amnesia.

PMID- 10928747
TI  - Verbal learning strategies in Parkinson's disease.
AB  - Word-list learning was studied in patients with Parkinson's disease (PD) and
      normal control (NC) participants by means of the selective-reminding procedure of
      H. Buschke and P. A. Fuld (1974) in 3 learning conditions using semantically
      unrelated items; semantically related items, whose implicit categorical structure
      had to be spontaneously guessed; and semantically related items, whose explicit
      categorical structure was known in advance. The PD patients displayed poor
      learning in all 3 conditions. To identify the functional locus of the PD
      patients' deficits, the authors performed a stochastic Markov chain analysis,
      which allowed individual measurements of encoding, retrieval, and category
      clustering abilities. PD patients were never significantly impaired in encoding
      word engrams; their impairment was confined to automatic and intentional
      retrieval and to the ability to benefit from explicit semantic clues.

PMID- 10928748
TI  - Task set switching in schizophrenia.
AB  - The authors used a task-switching paradigm to investigate set shifting ability in
      schizophrenia. This paradigm included 2 choice reaction time (RT) tasks: up-down
      and right-left. Switching tasks were associated with costs (i.e., longer RT in
      task-switch trials than in task-repetition trials); patients responded more
      slowly than controls and suffered greater switching costs, were as efficient as
      controls in engaging in an upcoming task set, and were faster than controls in
      disengaging from the previous task set. There were indications that patients
      quickly forgot what each keypress indicated, making it necessary for them to
      acquire response meaning information anew in each trial. To test this notion, the
      authors subsequently tested normal participants in conditions in which response
      meaning information needed to be acquired anew in each trial. These participants
      produced a pattern of switching costs resembling that of patients. Results
      suggest that set switching difficulties in schizophrenia, as exhibited in the
      present paradigm, reflect poor memory for task context information.

PMID- 10928749
TI  - Bowman's layer structure and function: critical or dispensable to corneal
      function? A hypothesis.
AB  - PURPOSE: The purpose of this article is to review available information regarding
      development, structure, and function of Bowman's layer in the cornea. Disease
      related abnormalities of Bowman's layer are described. A hypothesis is advanced
      to explain the development and maintenance of Bowman's layer. METHODS: Literature
      review and hypothesis formulation based on previous studies. RESULTS: Information
      is presented that supports the hypothesis that Bowman's layer forms as a result
      of cytokine-mediated interactions occurring between corneal epithelial cells and
      keratocytes that include chemotactic and apoptotic effects on the keratocytes.
      This hypothesis suggests that Bowman's layer results from such interactions
      beginning in early development and continuing into adulthood in humans and other
      animals, such as chickens. CONCLUSIONS: Bowman's layer may be a visible indicator
      of ongoing stromal-epithelial interactions in the human and have no critical
      function in corneal physiology. Bowman's layer is commonly destroyed in diseases
      such as advanced bullous keratopathy where stromal-epithelial interactions may be
      interrupted. Bowman's-like layers often form in response to epithelium, for
      example when epithelial plugs extend into the stroma in corneas with radial
      keratotomy incisions.

PMID- 10928750
TI  - Successful transplantation of bioengineered tissue replacements in patients with
      ocular surface disease.
AB  - PURPOSE: To bioengineer a corneal surface replacement using ex vivo expanded,
      cultured corneal epithelial stem cells seeded on a matrix derived from amniotic
      membrane and use this bioengineered graft to manage difficult ocular surface
      disease. METHODS: Fourteen patients with ocular surface disease unresponsive to
      standard medical and surgical treatments, including seven patients with presumed
      limbal stem cell deficiency were chosen for transplantation of a bioengineered
      composite corneal surface in eye each. Presumed corneal stem cells were harvested
      from either the patient's or related donor's limbus, expanded ex vivo, and
      cultivated on a carrier of modified human amniotic membrane. The resulting
      composite cultured tissue was transplanted to the ocular surface of the diseased
      eye, from which the abnormal tissue had been surgically removed. Ten patients
      received autologous grafts, and four received allogeneic grafts. RESULTS: A
      successful outcome, defined as restoration or improvement of vision, along with
      maintenance of corneal re-epithelialization and absence or recurrence of surface
      disease was obtained in 6 of the 10 patients with autologous procedures and in
      all 4 allogeneic transplants. Follow-up ranged 6-19 months with a mean of 13
      months. CONCLUSIONS: This novel technique documents that presumed corneal
      epithelial stem cells can be harvested safely from the limbus, expanded
      successfully in vitro, and grown on denuded amniotic membrane. The resultant
      composite cultured tissue can be transplanted and appears to successfully manage
      eyes with difficult ocular surface disease, including those with stem cell
      deficiency. This technique minimizes the threat of damage or depletion to the
      contralateral or donor limbus.

PMID- 10928751
TI  - A quick surgical technique for deep, anterior lamellar keratoplasty using visco
      dissection.
AB  - PURPOSE: To describe a new surgical technique for deep, anterior lamellar
      keratoplasty using a viscoelastic for dissection of Descemet's membrane (DM) from
      the posterior stroma. METHODS: Through a paracentesis, aqueous was exchanged by
      air to visualize the posterior corneal surface-i.e., the air-to-endothelium
      interface. Using the interface as a reference plane, a 30 gauge needle was
      inserted into the cornea to just anterior to DM. Viscoelastic was injected to
      separate DM from the posterior stroma, and a recipient, anterior lamella was
      excised. A full-thickness donor button was sutured into the recipient bed, after
      stripping its DM. RESULTS: In 25 eye bank eyes, the procedure could be completed
      in 20 eyes; in 5 eyes, DM ruptured during visco-dissection. With light
      microscopy, dissection depth was located at the level of DM. In two patient eyes
      the procedure could be completed. In a third patient eye DM ruptured during visco
      dissection, and the procedure was converted into a penetrating keratoplasty.
      CONCLUSION: Using visco-dissection, a lamellar keratoplasty can be performed
      quickly, with the donor-to-recipient interface just above the recipient DM, i.e.,
      with a nearly perfect anatomical replacement of all corneal stroma. There is
      substantial risk of rupture or microperforation of DM during surgery.

PMID- 10928752
TI  - Contrast and glare testing in the assessment of visual performance of candidate
      eyes for penetrating keratoplasty.
AB  - PURPOSE: To determine whether visual acuity (VA) measurements performed at low
      levels of contrast and glare are a better diagnostic tool for determining whether
      corneal clouding warrants surgery. METHODS: Fifty-nine subjects were recruited
      from among the candidates for corneal graft. Monocular VA was measured with three
      Regan contrast VA charts: 96, 25, and 11%, with and without glare provided by the
      Brightness Acuity Tester (BAT). The discriminative ability of the tests was
      estimated using the area (AR) under receiver operating characteristic (ROC)
      curves. Associations between the different VA tests and the Visual Function Index
      (VF-14) score were studied, using Spearman coefficients. RESULTS: When comparing
      candidate eyes with contralateral eyes with corneal disease, lower contrasts VA
      tests provided greater discriminative power. VA measurements made with glare also
      tended to provide greater discrimination. In fact, discrimination was best with
      11% contrast VA with glare, but "testability" was poor. The most practical test
      in a clinical setting, which retained high discriminative ability (0.798), was
      the 25% contrast VA with glare. The eye with the best VA correlated strongly with
      the VF-14, especially at 25% contrast without glare, resulting in an Rs of 
      0.729. CONCLUSION: Twenty-five percent contrast VA with BAT could help the
      practitioner to decide whether a corneal transplant is warranted when symptoms of
      reduced vision are more important than what high-contrast VA might indicate.

PMID- 10928753
TI  - Complications with one-piece lamellar keratolimbal grafts for simultaneous limbal
      and corneal pathologies.
AB  - PURPOSE: To determine the efficacy of a one-piece lamellar keratolimbal graft for
      the treatment of ocular surface disorders involving the limbus and cornea.
      METHODS: A retrospective study of a case series including eight patients with
      either Stevens-Johnson syndrome (four patients), ocular cicatricial pemphigoid
      (three patients), or familial subepithelial amyloidosis of the cornea (one case)
      was performed with a mean follow-up period of 18 months after surgery. RESULTS:
      Of the eight cases, three patients retained a corneal epithelial appearance upon
      their latest visit. No statistically significant difference was observed between
      preoperative visual acuity (0.013) and postoperative acuity (0.082). Stromal
      neovascularization was observed in all cases. Seven of eight cases experienced
      persistent epithelial defects (PED), four of which evolved secondary infectious
      ulcers. Two cases required further surgical intervention to treat PED or
      infectious ulcers. None of the cases developed glaucoma. CONCLUSION: A one-piece
      keratolimbal graft does not seem to offer any advantage over a two-piece limbal
      and corneal graft in the treatment of severe ocular surface disorders involving
      the limbus and cornea.

PMID- 10928754
TI  - Clinical and pathologic findings in human keratolimbal allograft rejection.
AB  - OBJECTIVE: To characterize the clinical and pathologic features of cadaveric
      keratolimbal allograft (KLAL) rejection. DESIGN: The study design is descriptive.
      PARTICIPANTS: Four patients (five eyes) with KLAL rejection are reported.
      INTERVENTION: All patients were subjected to slit-lamp biomicroscopy, treatment
      of rejection, and ultimately required repeat KLAL surgery. In three patients
      (four eyes), specimens obtained at the time of repeat surgery were subjected to
      immunohistochemical staining against the following immune and surface human
      antigens: CD4, CD8, CD19, CD3, DR, CK19, CK3, and vimentin. RESULTS: Signs of
      allograft rejection included intense sectoral injection, diffuse or perilimbal
      conjunctival injection, edema, and infiltration of the KLAL grafts, leading to
      punctate epithelial erosions, epithelial defects, and surface keratinization.
      Rejected specimens revealed T-lymphocyte infiltration (CD4:CD8, 2:1) with strong
      HLA-DR (MHC class II) expression. The epithelium stain results were positive for
      cytokeratin 19 and weakly positive to absent for cytokeratin 3. The epithelial
      stain results were weakly positive for vimentin in only one specimen.
      CONCLUSIONS: KLAL rejection is a newly recognized entity. Pathologic findings of
      rejected specimens indicate that this is a T-cell mediated rejection phenomenon.
      The pattern of cytokeratin staining provided little evidence that the epithelium
      covering KLALs had a corneal phenotype. The scarcity of vimentin-positive
      epithelial cells suggests that the stem-cell/transient-cell pool was probably
      depleted. Early recognition of clinical rejection is important, as treatment with
      immunosuppressive therapy may reverse the process.

PMID- 10928756
TI  - Infectious keratitis in climatic droplet keratopathy.
AB  - PURPOSE: To report the ulcer characteristics, microbiologic data, and outcome of
      infectious keratitis associated with climatic droplet keratopathy (CDK),
      suggesting that CDK is a predisposing factor for infectious keratitis. METHODS:
      Medical records of 32 patients (34 eyes) in whom infectious keratitis was seen in
      association with CDK were retrospectively reviewed. Data were collected regarding
      the nature of CDK lesions, infiltrate characteristics, organisms isolated, and
      outcome. RESULTS: CDK was peripheral in 16 (47.1%) eyes, central in 8 (23.5%),
      and diffuse in 10 (29.4%). The CDK lesions were nodular and elevated in all eyes.
      The infiltrate was adjacent to the CDK lesions in 28 eyes (82.4%). The infiltrate
      size (widest dimension) ranged 2-6 mm in 18 eyes (52.9%) and was >6 mm in 7
      (20.5%). The infiltrate was full thickness in 15 eyes (44.1%) and was involving
      up to the middle third of the corneal stroma in another 18 (52.8%). Hypopyon was
      seen in all. Bacteria were commonly isolated. Staphylococcus epidermidis (six
      eyes) and Streptococcus pneumoniae (five eyes) were the common bacteria isolated.
      Resolution with medical treatment was seen in 20 (58.8%) eyes. CONCLUSIONS: CDK
      is a predisposing factor for infectious keratitis. Treatment should be considered
      for advanced and nodular lesions, even if they are peripheral, to prevent
      infectious keratitis.

PMID- 10928755
TI  - Propionibacterium acnes as a cause of visually significant corneal ulcers.
AB  - PURPOSE: To report Propionibacterium acnes as a cause of vision-threatening
      infectious keratitis and to discuss culture isolation and antibiotic treatment.
      METHODS: Retrospective case series presentation collected from three academic
      medical centers. RESULTS: Six cases of P. acnes infectious keratitis are
      presented, all of which were associated with a compromised corneal barrier or
      environment. All cases were culture-positive on thioglycolate broth; none became
      positive before 7 days of growth. No other organisms were isolated from any
      culture, and the growth of P. acnes occurred in some cases despite negative gram
      stains. CONCLUSION: P. acnes can produce vision-debilitating keratitis when the
      cornea is compromised. Growth in culture should be monitored for at least 10 days
      to ensure isolation of this fastidious organism. P. acnes may respond to several
      different antibiotics that have gram-positive coverage, but it should be treated
      with vancomycin to enhance clearance of the organism.

PMID- 10928757
TI  - Comparison of antibiotic drops placed in the conjunctival cul-de-sac to
      antibiotic ointment applied to the lid margin in reduction of bacterial
      colonization on the lid margin.
AB  - PURPOSE: To compare the efficacy of antibiotic drops placed in the conjunctival
      cul-de-sac to antibiotic ointment applied to the lid margin in reduction of
      bacterial colonization on the lid margin. METHODS: A randomized, prospective,
      single-masked study was conducted on 19 patients with culture-proven colonization
      of bacteria on the lid margins. Ophthalmic eligibility criteria included the
      presence of > or =50 colony-forming units/mL (CFU/mL) of bacteria on both right
      and left lids. Each patient received one drop of ofloxacin in one eye every night
      for one week, followed by one drop once a week for one month. In the same manner,
      each patient received bacitracin ointment (erythromycin or gentamicin ointment if
      lid margin bacteria were resistant to bacitracin) to the lid margin of the fellow
      eye. Quantitative lid cultures were taken at initial visit, one week, one month,
      and two months. Fifteen volunteers (30 lids) served as controls. Lid cultures
      were taken at initial visit, one week, and one month. RESULTS: Both antibiotic
      drop and ointment reduced average bacterial CFU/mL at one week and one month.
      Average bacterial CFU/mL reestablished to baseline values at two months. There
      was no statistically significant difference between antibiotic drop and ointment
      in reducing bacterial colonization on the lid margin. CONCLUSION: Antibiotic
      drops placed in the conjunctival cul-de-sac appear to be as effective as ointment
      applied to the lid margins in reducing bacterial colonization in patients with >
      or =50 CFU/mL of bacteria on the lid margins.

PMID- 10928758
TI  - The reculture technique: individualizing the treatment of Acanthamoeba keratitis.
AB  - PURPOSE: To assess the efficacy of three drugs in different concentrations
      against different strains of Acanthamoeba using the reculture technique. METHODS:
      Cysts and trophozoites were immersed in five separate solutions. The solutions
      administered included 0.1% and 0.02% polyhexamethylene biguanide (PHMB), 0.1% and
      0.02% chlorhexidine, and propamidine isethionate (Brolene). Readings took place
      after 1, 5, and 24 hours. The cysts and trophozoites were then recultured for an
      additional period of 48 hours. An effective drug was defined as a medication that
      inhibited any growth of trophozoites using the reculture technique. RESULTS:
      Chlorhexidine at concentrations of 0.1% and 0.02% was the only effective drug
      against all five strains of Acanthamoeba examined, and no trophozoites were
      detected on plates immersed with this agent. Only 0.1% chlorhexidine was
      effective in destroying all cysts in the five strains examined. CONCLUSION: We
      found that 0.02% chlorhexidine was efficient in irradicating all trophozoites and
      0.1% chlorhexidine was effective in eradicating all cysts in the samples we
      examined. Therefore, it may be possible that 0.02% chlorhexidine is a good
      initial treatment in amoebic keratitis. Sensitivity testing, then, may be
      performed using the reculture technique and specification of therapy can be made
      accordingly.

PMID- 10928759
TI  - Penetrating keratoplasty in eyes with keratoconus and vernal
      keratoconjunctivitis.
AB  - PURPOSE: To determine the prognosis of penetrating keratoplasty in eyes with
      keratoconus and vernal keratoconjunctivitis. METHODS: The medical records of all
      patients with keratoconus and vernal keratoconjunctivitis who underwent
      penetrating keratoplasty at King Khaled Eye Specialist Hospital from January 1,
      1986 to December 31, 1996 and for whom at least 24 months' follow-up is available
      were analyzed retrospectively. RESULTS: Of 85 (61 males, 24 females) patients, 90
      eyes met the inclusion criteria. The mean follow-up was 44.7 (range, 26-144)
      months. At the most recent follow-up visit, 83 (92.2%) grafts were clear. The
      mean best corrected visual acuity was 20/40. Graft rejection episodes occurred in
      12 (13.3%) eyes, with irreversible graft failure occurring in 4 (4.4%) eyes.
      Bacterial keratitis occurred in 6 (7.7%) eyes, 2 (2.2%) of which developed
      irreversible graft failure. Herpes simplex keratitis resulted in irreversible
      graft failure in 1 (1.1%) eye. CONCLUSION: Penetrating keratoplasty in eyes with
      keratoconus and vernal keratoconjunctivitis has an excellent visual outcome and a
      low complication rate.

PMID- 10928760
TI  - Intraoperative mitomycin C in the treatment of pterygium.
AB  - PURPOSE: To evaluate the effectiveness of intraoperative mitomycin C in
      preventing the recurrence of primary pterygium. METHODS: In this prospective,
      randomized study, 38 eyes of 35 patients with primary pterygium were evaluated.
      In 19 eyes, the "bare sclera technique" combined with intraoperative application
      of 0.2 mg/mL (0.02%) mitomycin C for five minutes was performed (mitomycin C
      treated group). The other 19 eyes--taken as control group--underwent surgical
      excision alone. Statistics were analyzed using the Mann-Whitney U test and the
      Fischer's exact test. RESULTS: Patients were 20-38 years of age. The mean age was
      25.29 +/- 5.08 in the mitomycin C treated group and 25.00 +/- 5.19 in the control
      group. During the mean follow-up of 17.04 months (range, 12-36 months; SD =
      5.89), 4 recurrences (21%) were observed in the mitomycin C treated group and 11
      (57.8%) in the control group. The difference between the two groups was
      significant (p = 0.045). No postoperative complication was encountered in both
      groups except for recurrences. CONCLUSION: Intraoperative mitomycin C was found
      to be effective in preventing the recurrence of primary pterygium.

PMID- 10928761
TI  - Levels of collagen degradation products (telopeptides) in the tear film of
      patients with keratoconus.
AB  - PURPOSE: Levels of collagen degradation products (telopeptides) in the tear film
      of patients with keratoconus were measured to study the release of telopeptides
      in the tears. METHODS: Tear samples were collected from 26 keratoconus patients
      and 36 age-similar human control subjects. Levels of telopeptides were quantified
      and compared between the two groups. RESULTS: The telopeptide level in tears from
      keratoconus patients was 2.5-fold higher than in tears from the control group.
      The telopeptide concentration was age-dependent in both groups. In tears from
      young people, telopeptide level was 2-fold higher than in tears from the older
      people. CONCLUSION: The tear film of patients with keratoconus contains higher
      levels of telopeptides than those of control subjects. Determination of
      telopeptide levels in tears could be useful for the follow-up of keratoconus
      development in patients.

PMID- 10928762
TI  - Frequency of dry eye diagnostic test procedures used in various modes of
      ophthalmic practice.
AB  - PURPOSE: There are many suggested dry eye diagnostic test batteries in the
      literature. However, clinicians use a wide variety of dry eye diagnostic tests in
      clinical practice due to a number of factors, including time constraints. In
      addition, there has been no systematic description of the standard of care in
      diagnosing dry eye in the literature. The purpose of this study is to determine
      the type and frequency of dry eye diagnostic tests used in various modes of
      ophthalmic practice across a spectrum of dry eye severity. METHODS: A total of
      467 patient charts (patients with a previous dry eye diagnosis) were reviewed
      retrospectively to determine diagnostic test frequency. In reviewing patient
      charts, the following tests were identified as performed or not performed:
      symptom assessment, fluorescein staining, tear break-up time (TBUT), Schirmer
      test, rose bengal staining, and "tear assessment" (including quantity and quality
      of the tear meniscus). RESULTS: Dry eye diagnostic tests were used in the
      following frequencies across all modes of practice: symptom assessment (82.8%),
      fluorescein staining (55.5%), TBUT (40.7%), tear assessment (22.2%), Schirmer
      test (8.5%), and rose bengal staining (4.9%). When the clinics are pooled, two
      test procedures were used with the highest frequency (38.9%). The most commonly
      performed two-test procedure combination was a symptom assessment combined with
      fluorescein staining of the cornea (43.7%). CONCLUSIONS: Symptom assessment plays
      a large role in the diagnosis of dry eye. The current clinical standard of care
      for dry eye diagnosis includes the performance of at least one test procedure in
      addition to a symptom assessment.

PMID- 10928763
TI  - Survey of preferred tests for diagnosis of the tear film and dry eye.
AB  - PURPOSE: To survey practitioners in the tear film/dry eye field for their
      preferred diagnostic methods for the evaluation of the tear film and dry eye
      syndrome. METHODS: A survey was given to 36 optometrists and 41 ophthalmologists
      with backgrounds in the area of tear film and dry eye syndrome to find their
      preferred test if only one diagnostic option was available for tear film
      evaluation. Second, third, and fourth choices were also recorded, as well as any
      additional comments. RESULTS: Sixty-eight practitioners completed the survey. No
      one single test was a dominant first choice of the majority of respondents in
      either profession. History and/or dry eye questionnaire was the most frequent
      response to the question addressing the use of only one test (28%). The second
      most frequently chosen test was fluorescein break-up time (FBUT) (19%), followed
      by fluorescein staining (13%), and rose bengal (10%). The Schirmer test was most
      frequently included as one of the four choices (62%), although it was the first
      choice of only 9%. CONCLUSION: The importance of multiple tests in the evaluation
      of tear film disorders is overwhelmingly acknowledged, with patient history/dry
      eye questionnaires, FBUT, ocular surface staining, and the Schirmer test being
      the preferred diagnostic tools.

PMID- 10928764
TI  - Is there a correlation between the severity of diabetic retinopathy and
      keratoconjunctivitis sicca?
AB  - PURPOSE: Patients with diabetic retinopathy (DRP) seldom report symptoms of
      ocular surface irritation, but evaluations of dryness are pathologic. This study
      was designed to evaluate the correlation between the severity of DRP and dry
      eyes. METHODS: We included 144 eyes of 72 patients. Severity of retinopathy was
      graded according to the Early Treatment Diabetic Retinopathy Study. The
      examinations for dry eyes included Schirmer's test, break-up time, lipid layer
      thickness, fluorescein and rose bengal staining of the cornea, impression
      cytology, and a questionnaire. A sicca severity score was calculated using a
      point system of the results of these tests. Patients were divided into three
      groups: postpanretinal laser coagulation (PPL), postcentral laser coagulation
      (PCL), and those with no laser treatment (0-L). For statistics, we used the
      correlation coefficient to determine relationships and the unpaired Student t
      test for statistical difference. RESULTS: The correlation (c) of
      keratoconjunctivitis sicca (KCS) and DRP after laser treatment was c = 0.24 and
      after central laser treatment was c = 0.22; the correlation without laser
      treatment was 0.54. The best correlation is 1 or -1, the worst was 0. The score
      of those patients with mild to moderate retinopathy was compared to that of
      patients with severe to proliferative disease. There was a significant
      statistical difference in the sicca severity score between both groups, (p <
      0.006. Student t test). CONCLUSION: KCS represents another manifestation of
      diabetes mellitus and its severity--measured by a many-membered score--correlates
      with the severity of the DRP.

PMID- 10928765
TI  - Interleukin-6 levels in the conjunctival epithelium of patients with dry eye
      disease treated with cyclosporine ophthalmic emulsion.
AB  - PURPOSE: To evaluate interleukin-6 (IL-6) levels in the conjunctival epithelium
      of patients with moderate to severe dry eye disease before and after treatment
      with cyclosporin A ophthalmic emulsion (CsA) or its vehicle. METHODS:
      Conjunctival cytology specimens were obtained from a subset of patients enrolled
      in a 6-month randomized, double-masked clinical trial of the efficacy and safety
      of topical CsA at baseline and after 3 and 6 months of B.I.D. treatment with
      0.05% cyclosporine emulsion (n = 13), 0.1% cyclosporine emulsion (n = 8), or
      vehicle (n = 10). RNA was extracted and a competitive reverse transcriptase
      polymerase chain reaction (RT-PCR) was used to evaluate the levels of mRNA
      encoding the inflammatory cytokine IL-6 and a housekeeping gene, G3PDH. Levels of
      IL-6 and G3PDH were measured and compared. RESULTS: There was no change from
      baseline in the level of G3PDH after 3 or 6 months in any group. IL-6 normalized
      for G3PDH (IL-6/G3PDH ratio) was not different from baseline at 3 months but
      showed a significant decrease from baseline in the group treated with 0.05% CsA
      (p = 0.048) at 6 months. No significant between-group differences were noted and
      no correlation was observed between the change in IL-6/G3PDH and corneal
      fluorescein staining. CONCLUSIONS: This preliminary, small-cohort study showed a
      decrease in IL-6 in the conjunctival epithelium of moderate to severe dry eye
      patients treated with 0.05% CsA for 6 months. The observed decrease suggests that
      dry eye disease involves immune-mediated inflammatory processes that may be
      decreased by treatment with topical ophthalmic cyclosporine.

PMID- 10928766
TI  - The height and radius of the tear meniscus and methods for examining these
      parameters.
AB  - PURPOSE: To investigate the relationship between the radius of tear meniscus
      curvature (TMR) and tear meniscus height (TMH). METHODS: Twenty-nine eyes of dry
      eye patients (all left eyes; two males, 27 females, aged 26 to 85 years [mean +/-
      SD; 60 +/- 14.4]) were enrolled in the study. TMR was measured at the tear
      meniscus of the central lower lid with a newly developed videomeniscometer. At
      the same region of the eye, TMHs were measured without fluorescein (TMH-M) and
      after 5 minutes with fluorescein (TMH-MF), using a slit lamp equipped with a
      micrometer. TMHs were also measured on cross-sectional photographs of the
      fluorescein-stained meniscus (TMH-P). RESULTS: The values of TMR, TMH-M, TMH-MF,
      and TMH-P (mean +/- SD, mm) were 0.22 +/- 0.09, 0.19 +/- 0.09, 0.21 +/- 0.14, and
      0.24 +/- 0.09, respectively. There was significant correlation between TMR and
      TMH-M, TMH-MF, and TMH-P values (TMR versus TMH-M: r = 0.596, p = 0.0005; TMR
      versus TMH-MF: r = 0.587, p = 0.0006; TMR versus TMH-P: r = 0.605, p = 0.0003).
      CONCLUSION: There is a significant correlation between TMR and TMH.
      Videomeniscometry has some merits over conventional methods for obtaining tear
      meniscus parameters.

PMID- 10928767
TI  - Factors associated with corneal scarring in the Collaborative Longitudinal
      Evaluation of Keratoconus (CLEK) Study.
AB  - PURPOSE: The multicenter Collaborative Longitudinal Evaluation of Keratoconus
      (CLEK) Study is a prospective, observational study of 1,209 keratoconus patients.
      We report on the factors associated with corneal scarring at baseline. METHODS:
      We defined corneal scarring as scars that had been detected both by the clinician
      examining the patient with the slit-lamp biomicroscope and by masked readers of
      corneal photographs at the CLEK Photography Reading Center. We investigated
      associations between corneal scarring and patient variables including gender,
      ethnicity, a family history of keratoconus, a history of ocular trauma, eye
      rubbing, contact lens wear, rigid contact lens fitting relationships, and corneal
      findings (such as curvature, Vogt's striae, Fleischer's ring, and central/apical
      staining). Multiple logistic regression analysis using generalized estimating
      equations to adjust for the correlation between eyes was used for analysis.
      RESULTS: The following factors were found to increase the odds of corneal
      scarring at baseline in the CLEK Study: corneal staining (odds ratios (OR) =
      3.40, 95% confidence interval 2.53-4.59), contact lens wear (OR = 3.51, 95%
      confidence interval 2.27-5.45), Fleischer's ring (OR = 1.63, 95% confidence
      interval 1.11-2.40), steeper first definite apical clearance lens base curve
      radius (per diopter, OR = 1.29, 95% confidence interval 1.25-1.33), and age (per
      decade, OR = 1.54, 95% confidence interval 1.35-1.75). CONCLUSIONS: These
      baseline data suggest that corneal scarring in keratoconus is associated with
      corneal staining, contact lens wear, Fleischer's ring, a steeper cornea, and
      increasing age. The factors that imply added risk for corneal scarring that may
      be affected by practitioner intervention are staining of the cornea, contact lens
      wear, and the contact lens fitting relationship.

PMID- 10928768
TI  - Observation of corneal epithelial disturbance through soft contact lens using
      fluorescein dextran.
AB  - PURPOSE: To confirm the usefulness of fluorescein dextran as a vital dye for
      observing corneal epithelial disturbance through a medical-use soft contact lens.
      METHODS: Ten percent fluorescein isothiocyanate-dextran (FITC-dextran) was used
      as the staining dye. Patients with corneal epithelial disturbance who were
      wearing therapeutic soft contact lenses were observed using FITC-dextran.
      RESULTS: Through the soft contact lens, FITC-dextran enabled corneal disturbance
      observation similar to that seen with sodium fluorescein. In a case of corneal
      perforation, as well, positive Seidel's test was confirmed through the soft
      contact lens using this technique. CONCLUSION: FITC-dextran is considered a
      useful dye for examining the corneal epithelial condition without contact lens
      removal.

PMID- 10928769
TI  - Influence of refraction on tonometric readings after photorefractive keratectomy
      and laser assisted in situ keratomileusis.
AB  - PURPOSE: To determine the decrease of Goldmann tonometry after photorefractive
      keratectomy (PRK) and laser assisted in situ keratomileusis (LASIK) according to
      refraction prior to surgery. METHODS: Prospective simultaneous comparative case
      series of 53 myopic eyes (53 patients) that underwent PRK and 50 (50 patients)
      that underwent LASIK using the Summit Excimed SVS plus (Summit Technology, Inc.,
      Walthan, MA, U.S.A.). PRK and LASIK were subdivided by refractive error into two
      subgroups of more than or less than -5 diopters (D). Central tonometric readings
      were taken prior to surgery and 12 months after surgery. RESULTS: In LASIK and
      PRK subgroups of more than -5 D, 85.7% (24) and 69.6% (24), respectively, gave
      lower readings than those taken before surgery. In LASIK and PRK subgroups of
      less than -5 D, 77.3% (17) and 53.3% (16), respectively, gave lower readings. The
      difference between the two is significant (p < 0.001). Average tonometry falls by
      2.8 mmHG in the LASIK subgroup of more than -5 D (p < 0.001) and by 2.8 mmHG in
      the LASIK subgroup of less than -5 D (p < 0.001) and by 1.7 mmHG in the PRK
      subgroup of more than -5 D (p < 0.010). In PRK subgroup of less than -5 D, the
      tonometric changes are not significant (p = 0.971). CONCLUSIONS: High previous
      refraction (in PRK) and technique used determines lower final tonometric
      readings, bringing about more frequent and significant decreases in LASIK than in
      PRK for errors of more than and less than -5 D.

PMID- 10928770
TI  - Colorimetric indicators of microbial contamination in corneal preservation
      medium.
AB  - PURPOSE: To compare acid-base and oxidation-reduction indicators and to
      investigate the effect of buffer and temperature on the colorimetric detection of
      microbial growth in corneal preservation media. METHODS: Corneal preservation
      media containing gentamicin, without or with HEPES buffer, were prepared with
      either phenol red or AlamarBlue indicators (AccuMed International, Westlake, OH,
      U.S.A.). Both media were inoculated with Staphylococcus aureus, Streptococcus
      sanguis, Pseudomonas aeruginosa, Serratia marcescens, or Candida albicans and
      then incubated at 4 degrees C, 22 degrees C, or 35 degrees C. The pH or percent
      reduction were determined hourly for eight hours, then daily for one week.
      RESULTS: The length of time before a confirmed change in pH or reduction occurred
      varied by microorganism, storage temperature, and buffering capacity. At 4
      degrees C, none of the microorganisms caused a detectable pH change in buffered
      medium within one day after inoculation, although two bacterial species reduced
      AlamarBlue within four hours. At 22 degrees C and 35 degrees C, all bacteria
      except P. aeruginosa produced a pH shift within a few hours, and all tested
      bacterial species reduced AlamarBlue. For bacteria producing detectable pH
      changes, HEPES-buffered medium took longer to change than medium without HEPES.
      C. albicans was not detectable in HEPES-buffered medium at any temperature by
      phenol red and was only detectable by AlamarBlue after 2-3 days at 22 degrees C
      and 35 degrees C. CONCLUSION: Acidic shifts in refrigerated corneal preservation
      medium do not occur during contamination by several microorganisms. AlamarBlue, a
      redox indicator, is more sensitive than phenol red in detecting some bacteria. C.
      albicans is not reliably detected by pH or redox indicators.

PMID- 10928771
TI  - High-risk corneal allografts are capable of stimulating complement dependent
      cytolytic antibodies.
AB  - PURPOSE: To prospectively characterize serum antibody responses in high-risk
      corneal allografts. METHODS: Orthotopic and heterotopic C3H (H-2k) corneas were
      transplanted to CB6F1 (H-2b/d) recipient mice. Individual serum samples were
      collected at days 7, 14, 21, and 28 from orthotopically and heterotopically
      grafted mice. Samples were tested for anti-C3H antibodies using an enzyme-linked
      immunosorbent assay (ELISA). Serum samples were also tested for the ability to
      lyse target cells in the presence of complement. RESULTS: In high-risk donor-host
      combinations, 100% corneal allograft rejection occurs in the absence of IgG1
      production. Both orthotopic and heterotopic corneal allografts induced cytolytic
      complement fixing antibody isotypes. CONCLUSIONS: Allospecific corneal antibody
      may be involved in corneal graft rejection in high-risk donor-host combinations.

PMID- 10928772
TI  - Immunohistochemical localization of vascular endothelial growth factor,
      transforming growth factor alpha, and transforming growth factor beta1 in human
      corneas with neovascularization.
AB  - PURPOSE: To analyze presence and distribution of vascular endothelial growth
      factor (VEGF), transforming growth factor (TGF)alpha, and TGFbeta1 in human
      corneas with neovascularization due to different corneal diseases. METHODS:
      Indirect immunohistochemistry for VEGF, TGFalpha, and TGFbeta1, was performed on
      paraffin-embedded corneas obtained by keratoplasty. Corneas from each of the four
      main groups of histopathologic diagnoses associated with corneal
      neovascularization were analyzed (scarring after keratitis, graft
      rejection/insufficiency, acute necrotizing keratitis, scarring after
      mechanical/chemical injury). Subclassification of inflammatory infiltrates was
      done using immunohistochemistry for CD3 (T-lymphocytes) and CD68 (macrophages).
      RESULTS: The analyzed angiogenic factors were detectable in corneas from all four
      histopathologic groups in a similar distribution; capillary endothelial cells,
      stromal and intravascular inflammatory cells (T-lymphocytes, macrophages), and
      basal corneal epithelial cells stained positive for the tested angiogenic
      factors. CONCLUSION: The angiogenic factors VEGF, TGFalpha, and TGFbeta1 are
      detectable in human corneas with neovascularization. Their distribution is quite
      uniform in different corneal diseases, resulting in corneal angiogenesis. An
      antiangiogenic therapy inhibiting corneal neovascularization by antagonizing
      angiogenic factors would have to counteract several angiogenic factors.

PMID- 10928773
TI  - Ultrastructural changes in corneas of diabetic patients: an electron-microscopy
      study.
AB  - BACKGROUND: Although diabetic retinopathy has been thoroughly studied, little
      attention has been given to the corneal changes of diabetic patients.
      Pathophysiologic and clinical findings may be related to the ultrastructural
      changes found in these corneas. PURPOSE: To investigate the ultrastructural
      corneal changes of diabetic patients. PATIENTS AND METHODS: Transmission electron
      microscopic ultrathin sections were prepared from corneas of 16 noninsulin
      dependent diabetic patients (mean age, 65 years; range, 40-82 years) who suffered
      from the disease for a mean period of 22 years (range, 10-30 years). We used 16
      corneas from healthy age-matched donors as normal controls. RESULTS: In addition
      to the epithelial changes that include accumulation of glycogen granules,
      occasional focal epithelial cell degeneration, and irregular thickening and
      multilamination of the epithelial basement membrane, unusual 120-nm wide-spaced
      collagen fibril bundles were observed scattered among both Descemet's membrane
      and stromal matrix. CONCLUSIONS: The aggregates of wide-spaced collagen fibrils,
      which have not been described in other basement membranes of diabetic patients,
      may reflect an excessive glycosylation rate.

PMID- 10928774
TI  - In vitro pharmacodynamics of ofloxacin and ciprofloxacin against common ocular
      pathogens.
AB  - PURPOSE: Time-kill curve methodology was used to assess the pharmacodynamics of
      two fluoroquinolones, ofloxacin and ciprofloxacin, against six strains
      representing the most common ocular pathogens: Pseudomonas aeruginosa,
      Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae,
      Serratia marcescens, and Haemophilus influenzae. METHODS: For time-kill studies,
      ofloxacin and ciprofloxacin solutions were prepared at concentrations of 0.5 x,
      1.0 x, 2.0 x, and 3.0 x the MIC (minimal inhibitory concentration) for each
      respective strain. Inocula were prepared by diluting overnight cultures to final
      concentrations of 10(2), 10(3), 10(4), and 10(5) cfu (colony-forming units)/mL in
      each antibiotic solution. Growth controls were included. Viability counts of
      antibiotic-containing and control bacterial suspensions were performed at 0, 10,
      20, 30, 60, 90, 120, and 180 minutes. RESULTS: In general, the kill rates of
      ofloxacin at 1.0 x, 2.0 x, and 3.0 x the MIC were significantly faster than the
      kill rates of ciprofloxacin by approximately 30 minutes, regardless of the
      bacterial concentration tested. At 0.5 x MIC, the kill kinetics of ciprofloxacin
      and ofloxacin were similar, regardless of the strain tested. At 1.0 x MIC,
      ofloxacin achieved 99.9% killing of P. aeruginosa and S. aureus within 30
      minutes, and S. epidermidis and S. marcescens within 90 minutes. Overall, the
      kill kinetics of both quinolones for H. influenzae were similar, while neither
      quinolone achieved 99.9% killing of S. pneumoniae, regardless of the antibiotic
      concentration tested. CONCLUSION: Time-kill curve analyses in the present study
      demonstrate that ofloxacin achieved killing of the majority of ocular pathogens
      tested at rates equivalent to or faster than that of ciprofloxacin. Both
      fluoroquinolones were more effective against nonencapsulated bacteria than
      against encapsulated bacteria.

PMID- 10928775
TI  - The effect of povidone iodine on the corneal endothelium.
AB  - PURPOSE: Povidone iodine has been proven to be a valuable antiseptic solution in
      preparing the eye for surgery and is an alternative to postoperative topical
      antibiotics. No study has addressed the intraocular toxicity of povidone iodine
      after injection into the anterior chamber. We investigated the potential toxicity
      of povidone iodine on the corneal endothelium after injections into the anterior
      chamber in a rabbit model. METHODS: In this study we used 24 eyes of 12 albino
      rabbits. The eyes were divided into the following three groups according to the
      drugs tested: group A, 5% povidone iodine; group B, 10% povidone iodine; group C,
      balanced salt solution. The injected eyes were evaluated by biomicroscopy,
      specular microscopy, corneal pachymetry, and transmission and scanning electron
      microscopy. RESULTS: Corneal edema was observed in all eyes of groups A and B. In
      groups A and C, the endothelial cell morphology was not significantly changed and
      the mean endothelial cell count of the eyes did not change significantly (p =
      0.5054). There was no significant difference in corneal thickness between groups
      A and C (p = 0.3823), but there was a significant difference between groups B and
      C ( = 0.0002). Transmission and scanning electron microscopy results were normal
      in group C but not in groups A and B. CONCLUSION: Povidone iodine in both 5% and
      10% concentrations demonstrates severe toxicity when one drop of either
      concentration is placed directly in the anterior chamber. When povidone iodine is
      used in preparing the eye for intraocular surgery and as an alternative to
      postoperative antibiotics, the inadvertent leakage of povidone iodine into the
      anterior chamber must definitely be prevented.

PMID- 10928776
TI  - Epithelial barrier function and ultrastructure of gelatinous drop-like corneal
      dystrophy.
AB  - PURPOSE: Recently, mutations in the M1S1 gene have been identified as responsible
      for gelatinous drop-like corneal dystrophy (GDLD). How the abnormal M1S1 gene
      product causes GDLD is not known, although evidence suggests that it may
      compromise corneal epithelial function. This investigation attempted to determine
      the effect of the abnormal M1S1 gene product by assessing epithelial barrier
      function and epithelial ultrastructure in GDLD corneas. METHODS: Epithelial
      barrier function was assessed on the basis of fluorescein uptake. The method used
      a modified slit-lamp fluorophotometer. High-resolution scanning electron and
      atomic force microscopy was used to investigate the amyloid deposits and
      epithelial cell structure. RESULTS: Epithelial permeability was orders of
      magnitude higher in GDLD corneas than normal. The structure of the amyloid
      deposits was characterized, and clear abnormalities in epithelial morphology and
      cell junctions were observed. CONCLUSIONS: The high epithelial permeability
      observed in GDLD corneas was directly correlated with abnormalities in epithelial
      structure, including irregular cell junctions. This suggests that the abnormal
      M1S1 gene product may affect epithelial cell junctions resulting in increased
      cell permeability in GDLD corneas.

PMID- 10928777
TI  - Intracorneal inclusion of high-molecular-weight sodium hyaluronate following
      detachment of Descemet's membrane during viscocanalostomy.
AB  - PURPOSE: Viscocanalostomy in accordance with Stegmann's technique is a new
      surgical option in the treatment of glaucoma. There are few reports available
      describing the specific complications of viscocanalostomy. We report a case of
      intracorneal inclusion of high-molecular-weight sodium hyaluronate following
      viscocanalostomy. CASE REPORT: A 66-year-old man with uncontrolled primary open
      angle glaucoma of his right eye and a history of argon laser trabeculoplasty
      underwent viscocanalostomy in accordance with Stegmann's technique. During the
      filling of Schlemm's canal, a limited lysis of Descemet's membrane advanced
      centrally in the clear cornea adjacent to the site of canalostomy forming an
      intracorneal bubble of high-molecular-weight sodium hyaluronate. Postsurgical
      slit-lamp biomicroscopy showed an intracorneal clear bubble within the corneal
      periphery without evidence of adjacent corneal edema and with no contact between
      the corneal endothelium and the iris. Follow-up examinations determined that the
      appearance of the corneal inclusion, essentially, was unchanged, with only a
      slight tendency of resorption. No signs of corneal scarring or endothelial
      decompensation could be noted. CONCLUSION: To date, we could not determine a
      significant corneal damage in conjunction with the described complication.
      However, it is difficult to predict the long-term clinical course of our patient.
      Corneal decompensation as a result of possible endothelial toxicity of high
      molecular weight sodium hyaluronate as well as spontaneous absorption seem
      possible.

PMID- 10928778
TI  - Recurrent fungal keratitis and endophthalmitis.
AB  - PURPOSE: To report a case of recurrent fungal sclerokeratitis and endophthalmitis
      with a very successful outcome due to aggressive combined surgical and medical
      therapy. To discuss the management of this potentially devastating infection.
      METHODS: A 65-year-old man presented with 6 months of left eye redness and
      irritation after injury from organic matter propelled from an airboat. Initially,
      he had been treated with foreign body removal, antibiotics, and steroids. He was
      diagnosed with reactive sclerokeratitis at presentation and was treated with
      steroids. However, when he did not improve, cultures were obtained and Acremonium
      species filamentous fungi was identified. Despite treatment with appropriate
      topical and systemic antifungals, his fungal sclerokeratitis progressed to
      endophthalmitis. Two therapeutic penetrating keratoplasties (PKs) with iridectomy
      and intraocular amphotericin B were necessary to eradicate the fungal infection.
      RESULTS: Visual acuity was restored to 20/25-3 with correction 9 months after
      initial presentation. There was no recurrence of fungal infection after the
      second therapeutic PK. CONCLUSION: The possible reasons for recurrence of fungal
      infection are discussed. The role of timely and aggressive medical and surgical
      intervention for fungal sclerokeratitis and endophthalmitis in restoring
      excellent vision is emphasized.

PMID- 10928780
TI  - Remission of antiepiligrin (laminin-5) cicatricial pemphigoid after excision of
      gastric carcinoma.
AB  - PURPOSE: To describe a case of antiepiligrin cicatricial pemphigoid with unusual
      ocular manifestations and its remission after surgical removal of gastric
      carcinoma. METHODS: We describe a 61-year-old Japanese man with antiepiligrin
      cicatricial pemphigoid. RESULTS: He presented with conjunctival injection and
      discharge preceded by a 6-month period of erosive lesions in the oral mucosa and
      the truncal skin. An advanced gastric carcinoma was found and his serum
      immunoprecipitated laminin-5. Despite topical treatment with betamethasone,
      ofloxacin, and artificial tear solutions, serious symblepharon along the
      Meibomian line developed with little shortening of the inferior conjunctival sac.
      Following radical gastrectomy, the ocular and cutaneous lesions turned completely
      quiet. CONCLUSION: The present case differed from past cases by lacking inferior
      conjunctival sac shortening and by showing erosive lesions solely at the
      mucocutaneous junctions. The ocular involvement in this case correlated very well
      with the severity of gastric carcinoma.

PMID- 10928779
TI  - Corneal myxoma associated with keratoconus and Down's syndrome.
AB  - PURPOSE: Primary myxoma of the cornea is extremely rare. Until now, only four
      primary corneal myxomas were reported in the literature, whereas secondary
      involvement of the cornea by conjunctival and limbal tumors is much more common.
      METHODS: We report an additional case in a 26-year-old woman with keratoconus and
      Down's syndrome. Excision of the corneal mass was performed by penetrating
      keratoplasty. Histochemical, immunohistochemistry, and ultrastructural studies
      were used to obtain a definitive diagnosis. RESULTS: The tumor exhibited the
      characteristic histologic features of myxoma. The tumor cells showed
      immunoreactivity for vimentin but not for S-100 protein, epithelial membrane
      antigen, CAM 5.2, HHF-35, or muscle-specific actin. Ultrastructural features were
      fibroblast-like or stellate cells with cytoplasm containing abundant, rough
      reticulum and dilated cisternae. No recurrence was observed 36 months after
      penetrating keratoplasty. CONCLUSION: This is only the fifth report of such an
      occurrence. Although the coexistence of myxoma in Down's syndrome with
      keratoconus is described here for the first time, the differential diagnosis of
      apparently evident acute hydrops on clinical inspection should not rule out the
      possibility of a corneal myxoma. Histologic analysis should therefore be
      performed.

PMID- 10928781
TI  - Keratoconus associated with continual eye rubbing due to punctal agenesis.
AB  - PURPOSE: To highlight a possible causal effect of eye rubbing in the etiology of
      keratoconus. METHODS: A 43-year-old man presented to the practice of one of the
      authors (I.F.G.) with the complaint of gradual onset reading difficulty. History
      revealed the patient to have experienced constant epiphora in the right eye
      throughout his life as a result of punctal agenesis, which necessitated frequent
      wiping of this eye. Vision in the patient's right eye had been reduced for
      approximately 20 years. RESULTS: Based on ocular examination, the patient was
      diagnosed as having unilateral keratoconus in the right eye. CONCLUSION: It is
      thought by some that keratoconus is associated with, or indeed caused by,
      persistent rubbing of the anterior eye. While a number of studies support a
      genetic basis for keratoconus in some patients, it is possible that mechanical
      factors play a role in the development of this condition in other patients. This
      paper presents a case of unilateral keratoconus, where there is a confirmed
      history of habitual eye rubbing and wiping of excess tears as a result of punctal
      agenesis in the ipsilateral eye, thereby suggesting a possible causal
      relationship of eye rubbing in the etiology of keratoconus.

PMID- 10928782
TI  - Corneal amyloidosis associated with congenital hereditary endothelial dystrophy.
AB  - PURPOSE: To report the unusual occurrence of corneal amyloidosis
      indistinguishable from primary gelatinous drop-like dystrophy in three members of
      a family with congenital hereditary endothelial dystrophy (CHED). METHOD: Case
      study of three patients. RESULTS: Three patients, a 5-year-old girl, her 21-year
      old maternal aunt, and a 16-year-old paternal uncle, presented with bilateral
      corneal edema and opacification secondary to CHED. All three underwent
      penetrating keratoplasty, cases 1 and 3 in one eye and case 2 in both eyes.
      Histopathology confirmed the diagnosis of CHED in all three patients but also
      revealed multiple subepithelial nodular deposits of amyloid, consistent with the
      diagnosis of primary gelatinous drop-like dystrophy, in all four specimens. Three
      other members of the same family underwent penetrating keratoplasty with
      histologic confirmation of CHED with no deposits of amyloid. CONCLUSION: To our
      knowledge, this is the first report of subepithelial corneal amyloid deposits in
      association with CHED. This may represent the concurrence of two primary
      dystrophies, although secondary amyloidosis cannot be ruled out. Early
      manifestation and absence of amyloid in three other family members with CHED
      lends more weight to a primary etiology.

PMID- 10928783
TI  - Not who you know, but what you know.

PMID- 10928784
TI  - Bioinformatics meets data mining: time to dance?

PMID- 10928785
TI  - Evolution, not revolution.

PMID- 10928787
TI  - Primary care research.

PMID- 10928786
TI  - Steroid injections.

PMID- 10928788
TI  - Clinical skills assessments.

PMID- 10928789
TI  - Sertraline-induced hypomania presenting as hyperactivity disorder.

PMID- 10928790
TI  - Overrepresentation of aboriginal children in acute myeloid leukaemia: the
      experience of one institution.

PMID- 10928792
TI  - Proceedings of the 10th International Symposium on Pharmaceutical and Biomedical
      Analysis. Washington, DC, USA. May 9-12, 1999.

PMID- 10928791
TI  - The Royal College of Radiologists' Clinical Oncology Information Network.
      Guidelines for external beam radiotherapy.

PMID- 10928793
TI  - [Screening for diabetes mellitus at work places].

PMID- 10928794
TI  - [It is no more about cancer, but it is already about gene therapy].

PMID- 10928795
TI  - The 13th Annual International Mammalian Genome Society Conference: a meeting
      report.

PMID- 10928797
TI  - Neuromuscular disorders: gene location.

PMID- 10928796
TI  - Offspring sex ratio in heavily polluted town.

PMID- 10928798
TI  - 5th International Congress of the World Muscle Society. White River, South
      Africa, 25-29 June 2000. Abstracts.

PMID- 10928799
TI  - Practice Tips. Two-step Mantoux test.

PMID- 10928800
TI  - Proceedings of the ICRM Low-Level Radioactivity Measurement Techniques
      Conference. Mol, Belgium, October 1999.

PMID- 10928801
TI  - Gap junctions in the nervous system. Proceedings of a workshop. Rio de Janeiro,
      Brazil, 6-11 June 1998.

PMID- 10928802
TI  - Gap junctions in the nervous system.
AB  - Synapses are classically defined as close connections between two nerve cells or
      between a neuronal cell and a muscle or gland cell across which a chemical signal
      (i.e., a neurotransmitter) and/or an electrical signal (i.e., current-carrying
      ions) can pass. The definition of synapse was developed by Charles Sherrington
      and by Ramon y Cajal at the beginning of this century and refined by John Eccles
      and Bernard Katz 50 years later; in this collection of papers, the definition of
      synapses is discussed further in the chapter by Mike Bennett. who provided the
      first functional demonstration of electrical transmission via gap junction
      channels between vertebrate neurons. As is evidenced by the range of topics
      covered in this issue, research dealing with gap junctions in the nervous system
      has expanded enormously in the past decade, major findings being that specific
      cell types in the brain expresses specific types of connexins and that expression
      patterns coincide with tissue compartmentalization and function and that these
      compartments change during development.

PMID- 10928803
TI  - Connexins, hearing and deafness: clinical aspects of mutations in the connexin 26
      gene.
AB  - Congenital deafness is a very frequent disorder occurring in approximately I in
      1000 live births. Mutations in GJB2 encoding for gap junction protein connexin-26
      (Cx26) have been established as the basis of autosomal recessive non-syndromic
      hearing loss and proposed in some rare cases of autosomal dominant form of
      deafness. Connexin are gap-junction proteins which constitute a major system of
      intercellular communication important in the exchange of electrolytes, second
      messengers and metabolites. In the inner ear, connexin 26 expression was
      demonstrated in the stria vascularis, basement membrane, limbus and the spiral
      prominence of the human cochlea. The loss of connexin 26 in the gap junction
      complex would expect to disrupt the recycling of potassium from the synapses at
      the base of hair cells through the supporting cells and fibroblasts of potassium
      ions back to the high potassium containing endolymph of the cochlear duct and
      therefore would result in a local intoxication of the Corti s organ by potassium,
      leading to the hearing loss. The discovery of the genes responsible of hearing
      loss in particular the identification of mutations in the gene coding for
      connexin 26 allows to hope some tremendous help in genetic counseling. The
      possible implication of the mutation of the connexin gene in the pathophysiology
      of some progressive adult deafness opens new prospects in the fine diagnostic of
      the ear diseases and eventually may lead to new therapeutic strategies applied to
      the cochlea.

PMID- 10928804
TI  - A study of the frequency of contamination of products applied to the skin.

PMID- 10928805
TI  - Regarding conscious and deep sedation.

PMID- 10928806
TI  - Regarding the history of hair transplantation.

PMID- 10928807
TI  - Hereditary pancreatitis and mutations of the cationic trypsinogen gene.
AB  - BACKGROUND: Mutations of the cationic trypsinogen gene have been detected in
      hereditary pancreatitis. This article reviews current understanding of their
      function and clinical significance. METHODS: An unrestricted Medline search was
      conducted using the key words hereditary pancreatitis and 'cationic trypsinogen .
      Additional material was obtained from references cited in original papers and
      recently published abstracts of meetings. RESULTS AND CONCLUSION: Cationic
      trypsinogen mutations have been identified in most, but not all, families with
      hereditary pancreatitis. This confirms existing evidence that premature
      trypsinogen activation plays a central role in the pathogenesis of human
      pancreatitis. Patients currently clinically defined as having hereditary
      pancreatitis should be screened for the presence of cationic trypsinogen
      mutations. A subgroup of patients with non-hereditary pancreatitis may also
      benefit from being screened for these mutations. Patients with hereditary
      pancreatitis should be entered into prospective, multicentre trials investigating
      secondary screening for pancreatic cancer. Gene therapy for hereditary
      pancreatitis is beyond current technological capability but remains a future
      therapeutic prospect for this often debilitating condition.

PMID- 10928808
TI  - Duplex-guided thrombin injection for iatrogenic femoral artery pseudoaneurysm is
      effective even in anticoagulated patients.
AB  - BACKGROUND: The aim was to evaluate the efficacy and safety of percutaneous
      thrombin injection as an alternative non-operative method for treating
      postcatheterization femoral artery pseudoaneurysm in both anticoagulated and non
      anticoagulated patients. METHODS: Thirty consecutive patients with a femoral
      artery pseudoaneurysm secondary to radiological catheterization confirmed by
      duplex imaging were included. Thrombin 200-2000 units (1000 units/mi) in a
      titrating dose was injected into the centre of the cavity under duplex
      ultrasonographic guidance. Thrombosis was assessed in real time using B mode and
      colour flow. No sedation or anaesthesia was required during the procedure. The
      distal pulses and ankle pressures were evaluated before and immediately after the
      injection, to exclude propagation of thrombus into the femoral artery. RESULTS:
      Successful rapid thrombosis of the false cavity was induced in all 30 patients.
      There were no immediate or mid-term procedure-related complications, or
      recurrences at 6 weeks. Eighteen patients were anticoagulated therapeutically at
      the time and following the procedure with either heparin or warfarin. CONCLUSION:
      Percutaneous thrombin injection is a simple, quick, painless, safe and effective
      technique, particularly in patients taking anticoagulants.

PMID- 10928810
TI  - Some personal thoughts on plagiarism.

PMID- 10928809
TI  - Long-term results of arteriovenous fistulas using transposed autologous basilic
      vein.
AB  - BACKGROUND: The transposed autologous basilic vein to brachial artery
      arteriovenous fistula provides vascular access in the absence of adequate
      superficial vein. The long-term patency and complication rates of this conduit
      are largely unreported. PATIENTS AND METHODS: Seventy-four brachiobasilic
      fistulas were performed in 65 patients. This was a secondary or tertiary access
      procedure in 84 per cent of patients. RESULTS: Of the 74 fistulas performed, 50
      were successfully used for dialysis (68 per cent) and 24 (32 per cent) were never
      used, including 13 fistulas that failed without being used for dialysis. Of the
      74 fistulas, 46 per cent failed (n = 34), 10 patients died with a functioning
      fistula (n = 10) and five were transplanted. The 30-day secondary patency was 73
      per cent at 1 year, 53 per cent at 2 years and 43 per cent at 3 years rate was 96
      per cent. Cumulative secondary patency was 73 per cent at 1 year, 53 per cent at
      2 years and 43 per cent at 3 years. Nineteen (26 per cent) fistulas underwent a
      further 19 operative procedures. Fifty-one (69 per cent) fistulas developed
      complications. The most common complications were arm oedema (24 per cent),
      thrombosis (22 per cent) and bleeding (18 per cent). CONCLUSION: In high-risk
      patients the autologous transposed brachiobasilic fistula has equivalent patency
      and lower complication rates than those reported for polytetrafluoroethylene
      interposition grafts.

PMID- 10928811
TI  - [Medicine in the Russian Middle Ages].

PMID- 10928812
TI  - [Dr. Manuel Gonzalez Echevarria (1833-1898). A portrait].

PMID- 10928813
TI  - Balloon embolization of a post-traumatic carotid-jugular fistula.

PMID- 10928814
TI  - Coil embolization of a persistent sciatic artery aneurysm.

PMID- 10928816
TI  - Why do we force Canadians to study medicine abroad?

PMID- 10928815
TI  - An overview of the cell cycle arrest protein, p21(WAF1).
AB  - p21, also known as WAF1, Cip1, Sdi1, Mda 6 and Cap20 is a cell cycle protein that
      regulates and can arrest the cell cycle in G1 or S phase (either dependent or
      independent of p53). Its role may be pivotal in many cell processes including
      differentiation and apoptosis. This brief overview provides a summary of its
      presently known functions and indicates areas for further research, particularly
      in relation to oral malignant disease. Greater understanding of its role may lead
      to therapeutic advances in the management of malignant disease.

PMID- 10928817
TI  - When editors publish in their own journals.

PMID- 10928818
TI  - Occupational and para-occupational diseases in agriculture.

PMID- 10928819
TI  - Vitamin D analogs in cutaneous malignancies.
AB  - In this article are reviewed available experimental and clinical studies and
      vitamin D analogs, and molecular and cellular mechanisms of their antineoplastic
      activity. In more detail are discussed the antiproliferative and pro
      differentiative effects, inhibition of tumor-induced angiogenesis and induction
      of apoptosis. The use of vitamin D analogs is however hampered by their toxicity.
      In various experimental systems it was shown that the activities of vitamin D
      analogs can be enhanced by combined application with retinoids or other
      biological active compounds such as cytokines and growth factors. Retinoids and
      vitamin D analogs were found to have synergistic inhibitory effects on tumor cell
      proliferation and angiogenic capability, and both agents applied simultaneously
      are efficacious in small doses. Thus combined therapy could find application in
      clinical practice. There are up to now only very limited data on the treatment of
      cutaneous malignancies with vitamin D analogs and it appears that a combined
      therapy, preferably with retinoids, could be more beneficial. The new synthetic,
      more potent and less calcemic analogs might find wide application in chemotherapy
      of premalignant and early malignant cutaneous tumors and could be especially
      useful for chemoprevention in the high-risk groups, e.g., xeroderma pigmentosum,
      organ transplant recipients, arsenical keratoses and others.

PMID- 10928820
TI  - Plasma prolidase may be an index of liver fibrosis in the rat.

PMID- 10928821
TI  - Plasma extracellular-superoxide dismutase in healthy newborns and
      infants/children.

PMID- 10928822
TI  - A prediction of the size and evolutionary origin of the proteome of chloroplasts
      of Arabidopsis.

PMID- 10928823
TI  - Water ascent in plants: the ongoing debate.

PMID- 10928824
TI  - Special issue in memory of Gertrude B. Elion.

PMID- 10928825
TI  - Molecular diagnosis of Dirofilaria repens is not a dream.

PMID- 10928826
TI  - Ergogenic aids.

PMID- 10928827
TI  - Eating pattern and nutritional status of international elite flatwater paddlers.

PMID- 10928828
TI  - Predictive accuracy of Omron body logic analyzer in estimating relative body fat
      of adults.

PMID- 10928829
TI  - Microwaves and memory loss.

PMID- 10928830
TI  - Trichloroethylene health risks--state of the science.

PMID- 10928831
TI  - [Optimal lymph node number and occult lymph node metastases in colorectal cancer:
      the pathologist's view].

PMID- 10928832
TI  - When enthusiasm is infectious.

PMID- 10928833
TI  - Interaction of 6-mercaptopurine and azathioprine with 5-aminosalicylic acid
      agents.

PMID- 10928834
TI  - Wanted: a consensus nomenclature for cationic trypsinogen mutations.

PMID- 10928835
TI  - Ceftriaxone-resistant Salmonella infection from antibiotic-treated cattle.

PMID- 10928836
TI  - Promising cancer drug may be De-TRAILed by liver toxicity concerns.

PMID- 10928837
TI  - Physical and chemical cooperation between somatostatin and dopamine receptors.

PMID- 10928838
TI  - Image of the month. A diagnosis of bowel infarction was made, based on the
      clinical findings of acute abdomen and the CT appearance.

PMID- 10928839
TI  - All-Polish Symposium. Delivery at the end of the XX century. Wroclaw--Polanica
      Spa. April 7-8 2000.

PMID- 10928840
TI  - Trypsinogen mutations in hereditary pancreatitis: which nomenclature is
      convenient?

PMID- 10928841
TI  - [Dysfunctional uterine bleeding--etiology, mechanism, management and treatment].

PMID- 10928842
TI  - [50th anniversary of the Israel Defence Forces Medical Corps].

PMID- 10928843
TI  - The emergence of conformal radiotherapy: special implications for pediatric neuro
      oncology.

PMID- 10928844
TI  - Radiation Oncology in China: the third survey of personnel and equipment in
      radiation oncology.

PMID- 10928845
TI  - Regarding, Kubo, Coursey, Hanson et al., IJROBP 1998; 40:697-702.

PMID- 10928846
TI  - The slope of the sigmoid dose response curve for tumor control.

PMID- 10928847
TI  - Regarding Grado et al. IJROBP 1998;42:289-98.

PMID- 10928848
TI  - The proteasome: a molecular target for cancer therapy.

PMID- 10928849
TI  - An unusual coma after therapy for bone pain.

PMID- 10928850
TI  - Standardized comprehensive assessment for end-of-life and palliative care.

PMID- 10928851
TI  - Re: The relative potentcy between high-dose oral oxycodone and intravenous
      morphine.

PMID- 10928852
TI  - Nebulized scopolamine.

PMID- 10928853
TI  - Fine molecular mapping of the 4p16.3 aneuploidy syndromes in four translocation
      families.

PMID- 10928854
TI  - Investigation of meiotic rearrangements in DGS/VCFS patients with a microdeletion
      22q11.2.

PMID- 10928855
TI  - Pure trisomy 20p resulting from isochromosome formation and whole arm
      translocation.

PMID- 10928856
TI  - A SALL1 mutation causes a branchio-oto-renal syndrome-like phenotype.

PMID- 10928857
TI  - New MR/MCA syndrome with distinct facial appearance and general habitus, broad
      and webbed neck, hypoplastic inverted nipples, epilepsy, and pachygyria of the
      frontal lobes.

PMID- 10928859
TI  - Two further cases of Sener syndrome: frontonasal dysplasia and dilated Virchow
      Robin spaces.

PMID- 10928858
TI  - The mitochondrial genome in Wolfram syndrome.

PMID- 10928860
TI  - The psychological impact of a cancer family history questionnaire completed in
      general practice.

PMID- 10928861
TI  - Attitudes to genetic testing for breast cancer susceptibility in women at
      increased risk developing hereditary breast cancer.

PMID- 10928862
TI  - Attitudes of von Hippel-Lindau disease patients towards presymptomatic genetic
      diagnosis in children and prenatal diagnosis.

PMID- 10928863
TI  - Levelling-off of the risk of lung and bladder cancer in heavy smokers: an
      analysis based on multicentric case-control studies and a metabolic
      interpretation.
AB  - The shape of the dose-response relationship between carcinogenic exposure and
      cancer risk is a key issue, both from a theoretical (models of carcinogenesis)
      and practical (risk assessment) point of view. Human populations exposed to
      Polycyclic Aromatic Hydrocarbons (PAH) via air pollution showed a non-linear
      relationship between levels of exposure and WBC-DNA adducts. Among highly exposed
      subjects, the DNA adduct level per unit of exposure was significantly lower than
      measured at environmental exposures. The same exposure-dose non-linearity was
      observed in lung DNA from rats exposed to PAH. We have analyzed 11 case-control
      studies on bladder cancer (4584 incident cases and 9360 hospital controls) and
      eight case-control studies on lung cancer (5092 incident cases and 6083
      population controls), conducted in Europe in recent years. All the studies
      collected detailed information on smoking histories with a similar methodology.
      We have estimated the relationship between the number of cigarettes smoked and
      the risk of cancer, with and without adjustment by duration of smoking. We have
      observed a levelling-off of the relationship between the number of cigarettes
      smoked and the relative risks for lung and bladder cancer, both in men and women.
      The levelling-off occurred at an odds ratio of about 5 for bladder cancer, while
      it occurs at about 20 for lung cancer (in men). A potential explanation for such
      levelling-off involves metabolic pathways and individual susceptibility. It has
      been suggested that some metabolic polymorphisms exert an effect that is more
      important at low levels of exposure.

PMID- 10928864
TI  - Smoking and pneumococcal disease.

PMID- 10928865
TI  - Coagulation factor XI and venous thrombosis.

PMID- 10928866
TI  - Herpes zoster.

PMID- 10928867
TI  - Herpes zoster.

PMID- 10928868
TI  - Herpes zoster.

PMID- 10928869
TI  - Herpes zoster.

PMID- 10928870
TI  - Death and the research imperative.

PMID- 10928872
TI  - Death and the research imperative.

PMID- 10928871
TI  - Death and the research imperative.

PMID- 10928873
TI  - Death and the research imperative.

PMID- 10928874
TI  - Death and the research imperative.

PMID- 10928875
TI  - Interstitial pneumonitis associated with sirolimus therapy in renal-transplant
      recipients.

PMID- 10928876
TI  - Fulminant myocarditis.

PMID- 10928878
TI  - Fulminant myocarditis.

PMID- 10928877
TI  - Fulminant myocarditis.

PMID- 10928879
TI  - Spontaneous pneumothorax.

PMID- 10928880
TI  - Spontaneous pneumothorax.

PMID- 10928881
TI  - Transmission of hepatitis A virus infection despite vaccination.

PMID- 10928882
TI  - Sedation and analgesia for procedures in children.

PMID- 10928883
TI  - Sedation and analgesia for procedures in children.

PMID- 10928884
TI  - Sedation and analgesia for procedures in children.

PMID- 10928885
TI  - HIV-1 and an HTLV-II-associated cutaneous T-cell lymphoma.

PMID- 10928886
TI  - Raw animal tissues and dietary supplements.

PMID- 10928887
TI  - Images in clinical medicine. Methemoglobinemia.

PMID- 10928888
TI  - The ethics of research in developing countries.

PMID- 10928889
TI  - The ethics of research in developing countries.

PMID- 10928890
TI  - The ethics of research in developing countries.

PMID- 10928891
TI  - The ethics of research in developing countries.

PMID- 10928892
TI  - The ethics of research in developing countries.

PMID- 10928893
TI  - The ethics of research in developing countries.

PMID- 10928894
TI  - A study in rural Uganda of heterosexual transmission of human immunodeficiency
      virus.

PMID- 10928895
TI  - A study in rural Uganda of heterosexual transmission of human immunodeficiency
      virus.

PMID- 10928896
TI  - Liver damage due to alendronate.

PMID- 10928897
TI  - Ehlers-Danlos syndrome type IV.

PMID- 10928899
TI  - Hepatic hemangioma.

PMID- 10928898
TI  - Ehlers-Danlos syndrome type IV.

PMID- 10928900
TI  - Ulcerative colitis in a sigmoid neovagina.

PMID- 10928901
TI  - Hemostatic suturing technique for uterine bleeding during cesarean delivery.
AB  - BACKGROUND: If medical management is unsuccessful in controlling postpartum
      hemorrhage, conservative surgical intervention or cesarean hysterectomy is
      required. TECHNIQUE: Hemostatic multiple square suturing using a straight number
      7 or number 8 needle and number 1 chromic catgut is a new surgical technique to
      approximate anterior and posterior uterine walls, especially in areas where there
      is heavy bleeding. It controls postpartum hemorrhage by attachment and
      compression of the hemorrhage site of the endometrium or myometrium. EXPERIENCE:
      We used this technique in 23 women with postpartum hemorrhages at cesarean who
      did not respond to conservative treatment. In all 23 cases, bleeding decreased
      markedly and hysterectomy was avoided. All resumed normal menstrual flow after
      surgery. In four cases, further pregnancy was achieved after this method was
      used. CONCLUSION: Hemostatic multiple square suturing is an easy, safe,
      conservative surgical alternative to hysterectomy for treating uncontrollable
      postpartum hemorrhage.

PMID- 10928902
TI  - Laparoscopy in patients following transverse rectus abdominis myocutaneous flap
      reconstruction.
AB  - BACKGROUND: We report our technique and experience performing laparoscopic pelvic
      surgery on four women after transverse abdominus rectus myocutaneous flap (TRAM).
      TECHNIQUE: Examination under anesthesia is performed on all patients in the low
      lithotomy position parallel with the floor. The abdominal aorta is palpated and
      outlined. A pneumoperitoneum is created either by umbilical or left upper
      quadrant Veress placement. Patients with an acceptable umbilical location undergo
      port placement through the incision of the umbilical relocation. Other options
      include left upper quadrant or paramedian placement avoiding the ligamentum teres
      vessels. Lateral operative ports (5 mm) are placed with reference to the
      transverse incision present, the pelvic pathology, and the location of the
      umbilicus. Techniques of electrocautery, intra- and extracorporeal suturing and
      knot tying, and clips are preferred to minimize port size. EXPERIENCE: Following
      unilateral or bilateral TRAM reconstruction, four consecutive breast cancer
      survivors underwent successful laparoscopic-assisted vaginal hysterectomy with
      oophorectomy using the periumbilical incision for trocar placement. The only
      complication was a superficial skin breakdown from an adhesive allergy that
      required 6 weeks for complete resolution. CONCLUSION: Laparoscopic pelvic surgery
      is feasible in women after TRAM reconstruction. Knowledge of anatomic and
      physiologic variations related to the TRAM procedure is necessary in planning a
      safe operation.

PMID- 10928903
TI  - Sentinel node detection in cervical cancer.
AB  - BACKGROUND: For superficial tumors such as melanoma, breast, and vulvar cancer,
      sentinel node detection prevents unnecessary extensive lymph node dissections.
      Sentinel node detection has not yet proved feasible in tumors, such as cervical
      cancer, that drain to deep pelvic lymph nodes. TECHNIQUE: We injected technetium
      99m colloidal albumin around the tumor allowing preoperative lymphscintigraphy
      and intraoperative gamma probe detection of sentinel nodes. For visual detection,
      blue dye was injected at the start of surgery. EXPERIENCE: In six of 10 eligible
      women who had Wertheim-Meigs operations for cervical cancer stage Ib, one or more
      sentinel nodes could be detected by scintigraphy. Intraoperative gamma probe
      detection was successful in eight of ten women, whereas visual detection found
      sentinel nodes in only four. They were found as far as the common iliac level.
      One woman had positive lymph nodes, of which one was a sentinel node. CONCLUSION:
      Identification of sentinel nodes using radionuclide is possible in women with
      cervical cancer and potentially identifies women in whom lymph node dissection
      can be avoided.

PMID- 10928904
TI  - A syringe adapter to facilitate aspiration at amniocentesis.
AB  - BACKGROUND: Syringes were developed for injection, not aspiration. We describe an
      adapter that attaches to a standard syringe and aspirates by advancement rather
      than withdrawal. TECHNIQUE: The adapter consists of a syringe barrel extension
      and an attachable finger grip. The adapter attached to a standard syringe allows
      aspiration by advancement rather than withdrawal, with the same hand motion used
      as with injection. EXPERIENCE: In a comparison of timed in vitro fluid aspiration
      by 10 practitioners, mean times for aspiration of 15 mL were 32.4 seconds (range
      24-45) with standard technique and 25.3 seconds (range 24-30) with the adapted
      syringe (P < .003, paired t test). Thirteen of 14 physicians who used the adapted
      syringe in vivo reported that much less effort was required, and one physician
      reported that a little less effort was required. Overall, eight practitioners
      reported that the adapted syringe made amniocentesis much easier and six found no
      difference between the two devices. CONCLUSION: This adapter converts a standard
      syringe to one permitting aspiration by advancement rather than withdrawal.
      Practitioner feedback was positive with regard to ease of use, degree of effort,
      and overall satisfaction.

PMID- 10928905
TI  - Periurethral collagen injection for stress incontinence with and without urethral
      hypermobility.

PMID- 10928906
TI  - Preventing perineal trauma during childbirth: a systematic review.

PMID- 10928907
TI  - Low fetal oxygen saturation at birth and acidosis.

PMID- 10928908
TI  - Anterior sacrospinous vaginal vault suspension for prolapse.

PMID- 10928910
TI  - Hypokalaemic paralysis.

PMID- 10928909
TI  - [Anesthesia with injection of cocaine into the spinal canal. 1900].

PMID- 10928911
TI  - Temporary cardiac pacing.

PMID- 10928912
TI  - A total eclipse of the sun.

PMID- 10928913
TI  - Phaeochromocytomas in VHL disease.

PMID- 10928914
TI  - Self-assessment questions.

PMID- 10928915
TI  - Proceedings of the meeting of the American Society for Stereotactic and
      Functional Neurosurgery. Snowbird, Utah, USA. July 8-10, 1999.

PMID- 10928916
TI  - Magnetic source imaging in stereotactic and functional neurosurgery.
AB  - Magnetic source imaging (MSI) combines the unique spatial and temporal functional
      accuracy of magnetoencephalography (MEG) with the anatomic and pathologic detail
      of magnetic resonance (MR). This relatively new method of evaluating brain
      function provides a preoperative mapping of brain function and brain structure by
      integrating the functional information of MEG with the structural information of
      MR. This results in data on actual neuronal interactions in clinical patients.
      The temporal and spatial accuracy of the MEG data, combined with the anatomic and
      pathologic specificity of MRI, results in the magnetic source image, which offers
      accurate knowledge of cortical functional organization, and is important in the
      surgical treatment of brain neoplasms, vascular malformations, and epilepsy. MSI
      allows the tracking of neuronal activity on the scale of milliseconds with
      millimeter accuracy, and continues to lead to new understanding of many
      functional brain disorders.

PMID- 10928917
TI  - [Status of science, research and technique of residential hygiene aspects of
      waste material removal and recycling. Proceedings of a meeting. 30 August-1
      September 1999].

PMID- 10928918
TI  - Independence of R/M/N focus formation and the presence of intact BRCA1.

PMID- 10928919
TI  - Air pollution. Evidence mounts that tiny particles can kill.
AB  - Four years ago, the U.S. Environmental Protection Agency (EPA) ignited a fire
      storm when it declared that tens of thousands of people were dying each year from
      breathing tiny particles of dust and soot--and issued tough new regulations to
      crack down on these pollutants. Industry groups and many scientists assailed the
      decision, arguing that the data underlying the new particulate matter standard
      were inconclusive at best, and industry took their case to court. Now, a long
      awaited study, by a group widely perceived to be politically neutral, comes in
      solidly behind the earlier EPA decision and strongly implicates particles in
      excess deaths.

PMID- 10928920
TI  - Astrobiology. Ames's proposal for lab triggers battle at NASA.

PMID- 10928921
TI  - Hypertension. Mutation points to salt recycling pathway.

PMID- 10928922
TI  - Plant science. New European group lobbies for support.

PMID- 10928923
TI  - DNA imaging. Getting a feel for genetic variations.
AB  - A team of researchers has come up with a novel atomic imaging microscope that may
      dramatically speed the task of linking genetic variants to diseases. The
      microscope is a modification of the popular atomic force microscope (AFM), which
      uses an ultrasharp tip to map surfaces of everything from computer chips to DNA
      at the atomic level. By using this molecule-sized tip, the researchers were able
      get their AFM to march down a strand of DNA and identify uniquely shaped reporter
      molecules engineered to tag the genetic variations.

PMID- 10928924
TI  - AIDS research. Italian scientists seek to reverse budget cuts.

PMID- 10928925
TI  - Conservation biology. Combined insults spell trouble for rainforests.
AB  - Scientists are now saying that a combination of interacting factors--including
      forest fragmentation, logging, and El Nino-driven drought--has altered the fire
      regimes of tropical forests and is changing regional climates and reconfiguring
      the landscape. These interactions are synergistic, they say--that is, the whole
      is greater than the sum of its parts. The concept provides a new paradigm for
      understanding the dynamics of fragmented rainforests and for approaching their
      conservation.

PMID- 10928926
TI  - Biomedicine. New insights into type 2 diabetes.
AB  - Researchers studying type 2 diabetes are optimistic that they are closing in on
      the elusive causes of the world's most prevalent metabolic disorder--although no
      one is willing to bet the bank on it. Using both biochemical and genetic
      approaches, diabetes researchers have identified multiple intracellular signaling
      pathways that appear to lie at the heart of this condition, which affects some
      250 million people worldwide and is the leading cause of blindness, kidney
      failure, and amputation among adults. And in the process, they have thrown out
      much of the dogma of the past 10 years.

PMID- 10928927
TI  - Taxonomy of the Dmanisi crania.

PMID- 10928928
TI  - Early mouse models of human diseases.

PMID- 10928929
TI  - Antipsychotics and working memory in schizophrenia.

PMID- 10928930
TI  - AIDS in a new millennium.
AB  - As we enter the new millennium the world is still facing the challenge of
      responding to the AIDS pandemic. A new report from the Joint United Nations
      Programme on HIV/AIDS presents the latest statistics on prevalence, spread, and
      impact of the disease. In their Perspective, Schwartlander and his colleagues
      discuss the newly released statistics and the strategies needed to combat the
      further spread of HIV/AIDS and to reduce prevalence in the most severely affected
      countries.

PMID- 10928931
TI  - Cell biology. Travel bulletin--traffic jams cause tumors.
AB  - All animal cells have a polarity, that is, different proteins are clustered in
      distinct domains of the plasma membrane and these regions carry out different
      jobs. As Peifer discusses in a lively Perspective, new work (Bilder et al.)
      identifies some of the molecular characters that direct proteins to their
      different cellular destinations.

PMID- 10928932
TI  - Plant genetics. A tomato gene weighs in.
AB  - What makes some people big and others small--obviously our genes, but which ones?
      Working out the complex of genes that control such quantitative traits in animals
      and plants is one of the big challenges facing geneticists. In his Perspective,
      Doebley discusses new results that identify the fw2.2 gene as one of the genes
      determining fruit size in the tomato (Frary et al.).

PMID- 10928933
TI  - Chemistry. Superacids--it's al lot about anions.
AB  - Superacids are powerful agents for protonating weak bases, with applications
      ranging from synthetic chemistry to batteries and fuel cells. DesMarteau explains
      in his Perspective that many superacids have undesirable properties, because
      after proton donation, the resulting anion may interact strongly with the
      protonated base or the solvent. Reed et al. report the discovery of a superacid
      that overcomes this problem. In the anion, charge is distributed efficiently over
      many atoms, reducing unwanted interactions.

PMID- 10928934
TI  - Molecular biology. Transposase team puts a headlock on DNA.
AB  - Transposable DNA elements jump from one location in the genome to another. But,
      the cut-and-paste molecular machinations that support this nomadic lifestyle are
      still being unraveled. In their Perspective, Williams and Baker at the
      Massachusetts Institute of Technology discuss new details of transposon
      relocation revealed through resolution of the structure of a transposase enzyme
      bound to DNA (Davies et al.).

PMID- 10928936
TI  - Bibliography of toxinology.

PMID- 10928937
TI  - The Kyoto encyclopedia of genes and genomes--KEGG.

PMID- 10928935
TI  - Veno- and arterio-occlusive tourniquets are not only harmful, they are
      unnecessary.

PMID- 10928938
TI  - Plant and animal genome VIII and agricultural microbes genome I.

PMID- 10928939
TI  - Why should exhaled nitric oxide be evaluated?

PMID- 10928940
TI  - Why not phenytoin.

PMID- 10928941
TI  - Association between elevated plasma fibrinogen and the small, dense low-density
      lipoprotein phenotype among postmenopausal women.

PMID- 10928942
TI  - Ophthalmological numismatics. A look at the past...

PMID- 10928944
TI  - Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity.
AB  - Nitroparacetamol (NCX-701) is a newly synthesized nitric oxide-releasing
      derivative of paracetamol. Following i.p. administration, nitroparacetamol
      inhibits carrageenan-induced hindpaw oedema formation (ED(50), 169.4 micromol kg(
      1)) and mechanical hyperalgesia (ED(50), 156 micromol kg(-1)) in the rat. In
      contrast, the parent compound, paracetamol, exhibits no significant anti-oedema
      activity in this model (ED(50)>1986 micromol kg(-1), i.p. ) and is markedly less
      potent than nitroparacetamol as an inhibitor of carrageenan-mediated hyperalgesia
      (ED(50), 411.6 micromol kg(-1), i.p.). In a second model of nociception
      (inhibition of acetic acid induced abdominal constrictions in the mouse),
      nitroparacetamol administered orally (ED(50), 24.8 micromol kg(-1)), was again
      considerably more potent than paracetamol (ED(50), 506 micromol kg(-1), p.o.).
      Thus, compared with paracetamol, nitroparacetamol not only exhibits augmented
      antinociceptive activity in both rat and mouse but, intriguingly, is also anti
      inflammatory over a similar dose range.

PMID- 10928945
TI  - Bile acids increase intracellular Ca(2+) concentration and nitric oxide
      production in vascular endothelial cells.
AB  - The effects of bile acids on intracellular Ca(2+) concentration [Ca(2+)](i) and
      nitric oxide production were investigated in vascular endothelial cells. Whole
      cell patch clamp techniques and fluorescence measurements of [Ca(2+)](i) were
      applied in vascular endothelial cells obtained from human umbilical and calf
      aortic endothelial cells. Nitric oxide released was determined by measuring the
      concentration of NO(2)(-). Deoxycholic acid, chenodeoxycholic acid and the
      taurine conjugates increased [Ca(2+)](i) concentration-dependently, while cholic
      acid showed no significant effect. These effects resulted from the first
      mobilization of Ca(2+) from an inositol 1,4,5-triphosphate (IP(3))-sensitive
      store, which was released by ATP, then followed by Ca(2+) influx. Both bile acids
      and ATP induced the activation of Ca(2+)-dependent K(+) current. Oscillations of
      [Ca(2+)](i) were occasionally monitored with the Ca(2+)-dependent K(+) current in
      voltage-clamped cells and Ca(2+) measurements of single cells. The intracellular
      perfusion of heparin completely abolished the ATP effect, but failed to inhibit
      the bile acid effect. Deoxycholic acid and chenodeoxycholic acid enhanced NO(2)(
      ) production concentration-dependently, while cholic acid did not enhance it. The
      bile acids-induced nitric oxide production was suppressed by N(G)-nitro-L
      arginine methyl ester, exclusion of extracellular Ca(2+) or N-(6-aminohexyl)-5
      chloro-l-naphthalenesulphonamide hydrochloride (W-7) and calmidazolium,
      calmodulin inhibitors. These results provide novel evidence showing that bile
      acids increase [Ca(2+)](i) and subsequently nitric oxide production in vascular
      endothelial cells. The nitric oxide production induced by bile acids may be
      involved in the pathogenesis of circulatory abnormalities in liver diseases
      including cirrhosis.

PMID- 10928946
TI  - Lack of nitric oxide- and guanosine 3':5'-cyclic monophosphate-dependent
      regulation of alpha-thrombin-induced calcium transient in endothelial cells of
      spontaneously hypertensive rat hearts.
AB  - While the expression and/or activity of endothelial nitric oxide synthase (eNOS)
      has been characterized in spontaneously hypertensive (SHR) and normotensive
      Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both
      strains, the effect of NO on intracellular calcium concentration ([Ca(2+)](i)) is
      still unknown. Coronary microvascular ECs were isolated from SHR and WKY and
      characterized. Immunocytochemistry and Western blot analysis showed that eNOS was
      similarly expressed in ECs from both strains. Measuring [Ca(2+)](i) by imaging
      analysis of fura-2-loaded cells, we demonstrated that alpha-thrombin (3-180 U l(
      1)) induced a superimposable dose-dependent calcium transient in ECs from both
      strains. In WKY ECs, S-nitroso-N-acetyl-DL-penicillamine (SNAP) dose-dependently
      (10 - 100 microM) and 0.1 microM atrial natriuretic factor (ANF) reduced the
      maximum and the decay time of alpha-thrombin-induced calcium transient. The
      inhibitory effects of SNAP and ANF were prevented by blocking cyclic GMP
      dependent protein kinase. Non selective eNOS inhibitors prolonged the decay time
      of alpha-thrombin-induced calcium transient, while the selective inducible NOS
      inhibitor 1400 W was ineffective. SNAP (100 microM) and 0.1 microM ANF increased
      cyclic GMP content up to 22.9 and 42.3 fold respectively. In SHR ECs, alpha
      thrombin-induced calcium transient was not modified by SNAP, ANF or eNOS
      inhibition. SNAP (100 microM) and 0.1 microM ANF increased cyclic GMP content up
      to 9. 3 and 51 fold respectively. In WKY ECs, SNAP dose-dependently (10 - 100
      microM) reduced also bradykinin-induced calcium transient, while in SHR ECs was
      ineffective. We concluded that in SHR ECs, the cyclic GMP-dependent regulation of
      calcium transient is lost.

PMID- 10928947
TI  - Direct effects of propylthiouracil on testosterone secretion in rat testicular
      interstitial cells.
AB  - The aim of this study was to investigate the mechanism by which propylthiouracil
      (PTU) exerts its inhibitory effects on the production of testosterone by rat
      testicular interstitial cells. The plasma testosterone concentration was
      decreased 60 and 120 min after an intravenous infusion of PTU (10 or 20 mg kg(
      1)), but the concentration of plasma T(4) was unaffected by the drug treatment.
      Exposure of anterior pituitary tissue to PTU (3-12 mM) in vitro did not affect
      either basal or gonadotropin-releasing hormone (GnRH)-stimulated luteinizing
      hormone (LH) release. PTU (3 - 12 mM) inhibited both the basal and the human
      chorionic gonadotropin (hCG, 0.05 i.u. ml(-1))-stimulated release of testosterone
      from rat testicular tissue in vitro; at the highest concentration tested (12 mM),
      it also inhibited the forskolin or 8-bromo-adenosine 3':5'-cyclic monophosphate
      (8-Br-cyclic AMP)-stimulated release of testosterone. The 25-OH-cholesterol (10(
      7)-10(-5) M)-stimulated release of pregnenolone and testosterone by the
      testicular interstitial cells was inhibited by PTU (12 mM, P<0.05). The results
      suggest that the inhibitory actions of PTU on testosterone secretion are exerted,
      at least in part, at the testicular level through a mechanism which is
      independent of thyroid status and which involves a reduction in P450scc activity
      and, hence, in the conversion of cholesterol to pregnenolone.

PMID- 10928948
TI  - Vanilloid receptors on capsaicin-sensitive sensory nerves mediate relaxation to
      methanandamide in the rat isolated mesenteric arterial bed and small mesenteric
      arteries.
AB  - In the present study, the vasodilator actions of methanandamide and capsaicin in
      the rat isolated mesenteric arterial bed and small mesenteric arterial segments
      were investigated. Methanandamide elicited concentration-dependent relaxations of
      preconstricted mesenteric arterial beds (pEC(50)=6.0+/-0.1, E(max)=87+/-3%) and
      arterial segments (pEC(50)=6.4+/-0.1, E(max)=93+/-3%). In arterial beds, in vitro
      capsaicin pre-treatment blocked vasorelaxation to 1 and 3 microM methanandamide,
      and reduced to 12+/-7% vasorelaxation to 10 microM methanandamide. Methanandamide
      failed to relax arterial segments pre-treated in vitro with capsaicin. In
      arterial beds from rats treated as neonates with capsaicin to cause destruction
      of primary afferent nerves, methanandamide at 1 and 3 microM did not evoke
      vasorelaxation, and relaxation at 10 microM methanandamide was reduced to 26+/
      4%. Ruthenium red (0.1 microM), an inhibitor of vanilloid responses, attenuated
      vasorelaxation to methanandamide in arterial beds (pEC(50)=5.6+/-0.1, E(max)=89+/
      1%). Ruthenium red at 1 microM abolished the response to 1 microM methanandamide,
      and greatly attenuated relaxation at 3 and 10 microM methanandamide in arterial
      beds. In arterial segments, ruthenium red (0.15 microM) blocked vasorelaxation to
      methanandamide, but not to CGRP. In arterial segments, the vanilloid receptor
      antagonist capsazepine (1 microM) inhibited, and the calcitonin gene-related
      peptide (CGRP) receptor antagonist CGRP(8 - 37) (3 microM) abolished,
      methanandamide-induced relaxations. CGRP(8 - 37), but not capsazepine, attenuated
      significantly relaxation to exogenous CGRP. These data show that capsaicin and
      ruthenium red attenuate vasorelaxation to methanandamide in the rat isolated
      mesenteric arterial bed and small mesenteric arterial segments. In addition,
      CGRP(8 - 37) and capsazepine antagonize responses to methanandamide in mesenteric
      arterial segments. In conclusion, vanilloid receptors on capsaicin-sensitive
      sensory nerves play an important role in the vasorelaxant action of
      methanandamide in the rat isolated mesenteric arterial bed and small mesenteric
      arterial segments.

PMID- 10928943
TI  - Protein kinase C isoenzymes: a review of their structure, regulation and role in
      regulating airways smooth muscle tone and mitogenesis.

PMID- 10928949
TI  - Low dose carvedilol inhibits progression of heart failure in rats with dilated
      cardiomyopathy.
AB  - The cardioprotective properties of carvedilol (a vasodilating beta-adrenoceptor
      blocking agent) were studied in a rat model of dilated cardiomyopathy induced by
      autoimmune myocarditis. Twenty-eight days after immunization, surviving Lewis
      rats (32/43=74%) were divided into three groups to be given 2 mg kg(-1) day(-1)
      (Group-C2, n=10) or 20 mg kg(-1) day(-1) (Group-C20, n=10) of carvedilol, or
      vehicle (0.5% methylcellulose, Group-V, n=12). After oral administration for 2
      months, body weight, heart weight (HW), heart rate (HR), rat alpha-atrial
      natriuretic peptide (r-ANP) in blood, central venous pressure (CVP), mean blood
      pressure (mean BP), peak left ventricular pressure (LVP), left ventricular end
      diastolic pressure (LVEDP), +/-dP dt(-1) and area of myocardial fibrosis were
      measured. Values were compared with those for normal Lewis rats (Group-N, n=10).
      Two out of 12 (17%) rats in Group-V died from day 28 to day 42 after
      immunization. No rat died in Groups-C2, -C20 and -N. Although the CVP, mean BP,
      LVP and +/-dP dt(-1) did not differ among the three groups, the HW, HR and r-ANP
      in Group-C2 (1.14+/-0.03, 339+/-16 and 135+/-31) and Group-C20 (1.23+/-0.04,
      305+/-8 and 156+/-24) were significantly lower than those in Group-V (1.36+/-0.04
      g, 389+/-9 beats min(-1) and 375+/-31 pg ml(-1), respectively). The LVEDP in
      Group-C2 was significantly lower than that in Group-V (7.4+/-1.4 and 12.2+/-1.2
      mmHg, respectively, P<0. 05). The area of myocardial fibrosis in Group-C2 was
      smaller than that in Group-V (12+/-1 and 31+/-2%, P<0.01). These results indicate
      that a low dose of carvedilol has beneficial effects on dilated cardiomyopathy.

PMID- 10928950
TI  - Veratridine induces apoptotic death in bovine chromaffin cells through superoxide
      production.
AB  - The molecular mechanisms involved in veratridine-induced chromaffin cell death
      have been explored. We have found that exposure to veratridine (30 microM, 1 h)
      produces a delayed cellular death that reaches 55% of the cells 24 h after
      veratridine exposure. This death has the features of apoptosis as DNA
      fragmentation can be observed. Calcium ions play an important role in veratridine
      induced chromaffin cell death because the cell permeant Ca(2+) chelator BAPTA-AM
      and extracellular Ca(2+) removal completely prevented veratridine-induced
      toxicity. Following veratridine treatment, there is a decrease in mitochondrial
      function and an increase in superoxide anion production. Veratridine-induced
      increase in superoxide production was blocked by tetrodotoxin (TTX; 10 microM),
      extracellular Ca(2+) removal and the mitochondrial permeability transition pore
      blocker cyclosporine A (10 microM). Veratridine-induced death was prevented by
      different antioxidant treatments including catalase (100 IU ml(-1)), N-acetyl
      cysteine (100 microM), allopurinol (100 microM) or vitamin E (50 microM).
      Veratridine-induced DNA fragmentation was prevented by TTX (10 microM).
      Veratridine produced a time-dependent increase in caspase activity that was
      prevented by Ca(2+) removal and TTX (10 microM). In addition, calpain and
      caspases inhibitors partially prevented veratridine-induced death. These results
      indicate that chromaffin cells share with neurons the molecular machinery
      involved in apoptotic death and might be considered a good model to study
      neuronal death during neurodegeneration.

PMID- 10928951
TI  - Disparate ligand-mediated Ca(2+) responses by wild-type, mutant Ser(200)Ala and
      Ser(204)Ala alpha(2A)-adrenoceptor: G(alpha15) fusion proteins: evidence for
      multiple ligand-activation binding sites.
AB  - Ligand : receptor interactions were analysed at wt, mutant Ser(200)Ala and
      Ser(204)Ala alpha(2A) ARs by measuring Ca(2+) responses in CHO-K1 cells either by
      co-expression with a G(alpha15) protein or at a receptor : G(alpha15) protein
      stoichiometry of 1.0 using fusion proteins. The magnitude of the UK 14304
      mediated Ca(2+) response as elicited by a G(alpha15) protein was largest with
      both mutant Ser(200)Ala and Ser(204)Ala alpha(2A)ARs compared to the wt alpha(2A)
      AR in the co-expression and fusion protein experiments. The activation profiles
      of the wt and both mutant alpha(2A) ARs as analysed by a series of alpha(2) AR
      agonists differed. d-Medetomidine and clonidine appeared most efficacious at the
      Ser(204)Ala alpha(2A) AR, whereas oxymetazoline was also partially active at the
      Ser(200)Ala alpha(2A) AR. Talipexole was silent at both mutant alpha(2A) ARs. The
      intrinsic activity of (-)-adrenaline was either absent or partial at the
      Ser(204)Ala and Ser(200)Ala alpha(2A) AR, respectively. This latter observation
      is related to its lower binding affinity for both mutant alpha(2A) ARs. Ligands
      characterized as antagonists at wt and Ser(200)Ala alpha(2A) ARs demonstrated
      either no intrinsic activity (i.e., RX 811059) or positive efficacy with a
      different rank order of maximal response at the Ser(204)Ala alpha(2A) AR
      (atipamezole=SKF 86466=idazoxan>dexefaroxan) than Asp(79)Asn alpha(2A) AR
      (atipamezole>idazoxan approximately SKF 86466>dexefaroxan) and Thr(373)Lys
      alpha(2A) AR (SKF 86466>atipamezole approximately idazoxan>dexefaroxan). These
      effects were only observed in the co-expression experiments at concentrations in
      line with their binding affinities. In conclusion, these Ca(2+) data suggest that
      multiple activation binding sites exist for these ligands at the alpha(2A) AR,
      and that their activation may be affected in different ways by the mutations
      being investigated.

PMID- 10928952
TI  - Effect of venotropic drugs on the respiratory activity of isolated mitochondria
      and in endothelial cells.
AB  - Several drugs used in the treatment of chronic peripheral ischaemic and venous
      diseases, i.e. aescine, Cyclo 3, Ginkor Fort, hydroxyethylrutosides,
      naftidrofuryl, naphthoquinone and procyanidolic oligomers, were tested on the
      mitochondrial respiratory activity. The results show that all these drugs
      protected human endothelial cells against the hypoxia-induced decrease in ATP
      content. In addition, they all induced a concentration-dependent increase in
      respiratory control ratio (RCR) of liver mitochondria pre-incubated with the
      drugs for 60 min. The drugs were divided into two groups according to their
      effects. The first group (A), comprising aescine, Ginkor Fort, naftidrofuryl and
      naphthoquinone, increased RCR by decreasing state 4 respiration rate. The second
      group of drugs (B), comprising hydroxyethylrutosides, procyanidolic oligomers and
      Cyclo 3, increased RCR by increasing state 3 respiration rate. The drugs of group
      A were able to prevent the inhibition of complexes I and III respectively by
      amytal and antimycin A while the first two drugs of group B increased adenine
      nucleotide translocase activity. Cyclo 3 inhibited the carbonylcyanide m
      chlorophenyl hydrazone (mCCP)-induced uncoupling of mitochondrial respiration.
      None of these seven drugs could protect complexes IV and V, respectively, from
      inhibition by cyanide and oligomycin. When tested on endothelial cells the drugs
      of group A, in contrast to group B, prevented the decrease in ATP content induced
      by amytal or antimycin A. The present results suggest that the protective effects
      on mitochondrial respiration activity by these venotropic drugs may explain their
      protective effect on the cellular ATP content in ischaemic conditions and some of
      their beneficial therapeutic effect in chronic vascular diseases.

PMID- 10928953
TI  - LU135252, an endothelin(A) receptor antagonist did not prevent pulmonary vascular
      remodelling or lung fibrosis in a rat model of myocardial infarction.
AB  - The early intervention with endothelin(A) (ET(A)) receptor antagonists following
      coronary artery ligation has been shown to reduce the development of pulmonary
      hypertension, despite a lack of improvement in left ventricular function. The
      present study examined the contribution of pulmonary vascular remodelling and the
      progression of lung fibrosis in the development of pulmonary hypertension and the
      subsequent role of endothelin-1 in these processes in a rat model of myocardial
      infarction (MI). The administration of 60 mg kg(-1) per day of the specific ET(A)
      receptor antagonist LU135253 ((+)-(S)-2-(4, 6-dimethoxy-pyrimidin-2-yloxy)-3
      methoxy-3,3-diphenyl-propionic acid) 24 h following coronary artery ligation,
      failed to improve left ventricular contractile indices, but reduced the extent of
      pulmonary hypertension, as reflected by the significant decrease in right
      ventricular systolic pressure. The medial wall thickness of small pulmonary
      arteries (50 - 200 microm) was significantly increased 4 weeks following MI,
      albeit LU135253 treatment did not ameliorate this pattern of vascular
      remodelling. The steady-state mRNA levels of collagen, fibronectin, transforming
      growth factor-beta(1), and -beta(3) were significantly increased in the lungs of
      MI rats. The treatment with LU135252 did not alter this pattern of gene
      expression. Thus, these data demonstrate pulmonary vascular remodelling and the
      increased expression of extracellular matrix proteins represent underlying
      mechanisms implicated in the development of pulmonary hypertension in the MI rat.
      Despite the amelioration of the pulmonary hypertensive state, ET(A) receptor
      blockade was insufficient to reverse pulmonary vascular remodelling, or the
      development of lung fibrosis in the MI rat.

PMID- 10928954
TI  - Cytotoxicity associated with induction of nitric oxide synthase in rat duodenal
      epithelial cells in vivo by lipopolysaccharide of Helicobacter pylori: inhibition
      by superoxide dismutase.
AB  - The products released by Helicobacter pylori (H. pylori) in the gastric antral
      and duodenal mucosa may be involved in mucosal ulceration by stimulating the
      local formation of cytotoxic factors such as nitric oxide (NO), superoxide or
      peroxynitrite. The present study investigates the ability of purified H. pylori
      lipopolysaccharide (LPS) to induce nitric oxide synthase (iNOS) in rat duodenal
      epithelial cells following in vivo challenge and its interaction with superoxide
      in promoting cellular damage and apoptosis. H. pylori LPS (0.75-3 mg kg(-1) i.v.
      or 3-12 mg kg(-1) p.o.) induced a dose - dependent expression of iNOS activity
      after 5 h in the duodenal epithelial cells, determined by [(14)C] arginine
      conversion to citrulline. The epithelial cell viability, as assessed by Trypan
      Blue exclusion and MTT conversion, was reduced 5 h after challenge with H. pylori
      LPS, while the incidence of apoptosis was increased. The iNOS activity and
      reduction in cell viability following H. pylori LPS challenge i.v. was inhibited
      by the selective iNOS inhibitor, 1400 W (0.2-5 mg kg(-1) i.v.). Concurrent
      administration of superoxide dismutase conjugated with polyethylene glycol (250 -
      500 i.u. kg(-1), i.v.), which did not modify the cellular iNOS activity, reduced
      the epithelial cell damage provoked by i.v. H. pylori LPS, and abolished the
      increased incidence of apoptosis. These results suggest that expression of iNOS
      following challenge with H. pylori LPS provokes duodenal epithelial cell injury
      and apoptosis by a process involving superoxide, implicating peroxynitrite
      involvement. These events may contribute to the pathogenic mechanisms of H.
      pylori in promoting peptic ulcer disease.

PMID- 10928955
TI  - Regulation of lymphocyte proliferation by eosinophils via chymotrypsin-like
      protease activity and adhesion molecule interaction.
AB  - We investigated the regulatory mechanisms responsible for release of eosinophil
      cationic protein (ECP) from eosinophils activated by platelet-activating factor
      (PAF) and monitored intra-cellular pH (pHi) changes using a pH-sensitive
      fluorescent probe. We also explored the mechanisms by which eosinophils suppress
      T-lymphocyte proliferation induced by phytohaemagglutinin (PHA). In these
      experiments, a separated culture to investigate the ECP-mediated pathway and a
      coculture to identify the adhesion molecules involved in eosinophil-lymphocyte
      interactions were employed. Chymostatin (1x10(-6) M) inhibited ECP release by
      about 50% via stimulation by PAF or recombinant interleukin 5(rIL-5) plus IgG.
      PAF (1x10(-7) M) raised eosinophil pHi from 6.9 to 7.3 within 20 s and
      pretreatment of these cells with chymostatin (1x10(-6) M), but not with leupeptin
      or E64-d, completely prevented this increase. Calcium ionophore A23187 (1x10(-7)
      M) induced ECP release and raised pHi to within a range similar to that of PAF,
      however, chymostatin had no effect on either. Chymostatin reversed ECP-mediated
      suppression of PHA-induced T-lymphocyte proliferation in separated cultures, but
      not in cocultures. In coculture, eosinophils exhibited the same level of
      suppression of both CD4(+) and CD8(+) T-cell proliferation in response to PHA.
      Monoclonal antibodies against CD11a, CD18 and CD54, but not CD11b, restored
      eosinophil suppression of T-lymphocyte proliferation which was chymostatin
      resistant in coculture. Eosinophils were unable to suppress the proliferative
      response to lymphocytes to anti-CD3 stimulation. In conclusion, chymostatin
      specifically inhibited both the eosinophil pHi increase and ECP release induced
      by PAF. Eosinophils regulate PHA-induced T-lymphocyte proliferation via the ECP
      mediation associated with chymotrypsin-like protease activity. These cells also
      control interactions with lymphocyte between adhesion molecules, CD11a, CD18 and
      CD54.

PMID- 10928956
TI  - Evidence against a role of inducible nitric oxide synthase in the endothelial
      protective effects of delayed preconditioning.
AB  - Preconditioning the heart with brief periods of ischaemia induces delayed
      endothelial protection against reperfusion injury, but the precise mechanisms
      involved in this endogenous protein are still unclear. Induction of the type II
      nitric oxide synthase (iNOS) acts as a mediator of the preconditioning against
      myocardial infarction and stunning. The present study was designed to assess
      whether iNOS also contributes to the delayed endothelial protective effects of
      preconditioning. Rats were subjected to 20 min ischaemia followed by 60 min
      reperfusion 24 h after sham surgery or preconditioning (one cycle or 2 min
      ischaemia/5 min reperfusion and two cycles of 5 min ischaemia/5 min reperfusion).
      At the end of the reperfusion, coronary segments were removed distal to the site
      of occlusion and mounted in wire myographs. Ischaemia-reperfusion (I/R) decreased
      the endothelium-dependent relaxations to acetylcholine (maximal relaxations:
      sham, 66+/-5%; I/R, 40+/-1%; P<0.05) and this impairment was prevented by
      preconditioning (maximal relaxation: 61+/-6%). Administration of N-(3
      aminomethyl)benzyl)acetaminide (1400W), a highly selective inhibitor for iNOS, 10
      min before prolonged ischaemia did not modify the beneficial effect of
      preconditioning (maximal relaxation: 66+/-5%). These data show that
      preconditioning induces delayed protection against reperfusion-injury. However,
      in contrast to the myocytes, these endothelial protective effects of delayed
      preconditioning do not involve iNOS.

PMID- 10928957
TI  - Hippocampal noradrenergic neurotransmission in concurrent EEG desynchronization
      and inhibition of penile erection induced by cocaine in the rat.
AB  - We previously reported that cocaine may induce activation of cortical (cEEG) and
      hippocampal (hEEG) electroencephalographic signals, concurrent with inhibition of
      penile erection, via an action on the hippocampal formation. The present study
      further evaluates the role of noradrenergic neurotransmission at the hippocampal
      formation in this process, using adult, male Sprague-Dawley rats anaesthetized
      and maintained by chloral hydrate. Unilateral microinjection of cocaine (100
      nmoles) into the hippocampal CA1 or CA3 subfield or dentate gyrus elicited
      significant activation of both cEEG and hEEG activity. At the same time, the
      intracavernous pressure (ICP), our experimental index for penile erection,
      underwent a discernible reduction. Co-administration of equimolar doses (250
      pmoles) of prazosin, naftopidil, yohimbine or rauwolscine significantly reversed
      those effects elicited by cocaine on cEEG, hEEG and ICP. Microinjection
      unilaterally of equimolar doses (5 nmoles) of norepinephrine, phenylephrine or
      BHT 933 into the hippocampal formation, similar to cocaine, also induced
      appreciable cEEG and hEEG excitation, with a simultaneous decrease in ICP. We
      conclude that cocaine may activate cEEG and hEEG and decrease ICP via
      noradrenergic neurotransmission, possibly engaging at least alpha(1A/D)-,
      alpha(2B)- and alpha(2C)-adrenoceptors at the hippocampal formation.

PMID- 10928958
TI  - Cholera toxin treatment of vascular smooth muscle cells decreases smooth muscle
      alpha-actin content and abolishes the platelet-derived growth factor-BB
      stimulated DNA synthesis.
AB  - The second messenger cyclic AMP regulates diverse biological processes such as
      cell morphology and cell growth. We examined the role of the second messenger
      cyclic AMP on rat aortic vascular smooth muscle cell (VSMC) morphology and the
      intracellular transduction pathway mediated by platelet-derived growth factor
      beta-receptor (PDGF-Rbeta). The effect of PDGF-BB on VSMCs growth was assessed by
      [(3)H]-thymidine incorporation. Tyrosine phosphorylation of PDGF-Rbeta, PLC
      gamma1, ERK1 and ERK2, p125(FAK) and paxillin as well as Sm alpha-actin was
      examined by the chemiluminescence Western blotting method. Actin mRNA level was
      quantitated by Northern blotting. Visualization of Sm alpha-actin filaments,
      paxillin and PDGF-Rbeta was performed by immunfluorescence microscopy. Cholera
      toxin (CTX; 10 nM) treatment lead to a large and sustained increase in the cyclic
      AMP concentration after 2 h which correlated with change of VSMC morphology
      including complete disruption of the Sm alpha-actin filament array and loss of
      focal adhesions. Treatment of VSMCs with CTX did not influence tyrosine
      phosphorylation of p125(FAK) and paxillin but decreased the content of a Sm alpha
      actin protein. Maximal decrease of 70% was observed after 24 h of treatment. CTX
      also caused a 90% decrease of the actin mRNA level. CTX treatment completely
      abolished PDGF-BB stimulated DNA-synthesis although PDGF-Rbeta level and
      subcellular distribution and translocation was not altered. Furthermore CTX
      attenuated the PDGF-BB-induced tyrosine phosphorylation of the PDGF-Rbeta, PI 3'
      K, PLC-gamma1 and ERK1/2 indicating an action of cyclic AMP on PDGF-beta
      receptor. We conclude that although cyclic AMP attenuates the PDGF-Rbeta mediated
      intracellular transduction pathway, an intact actin filament may be required for
      the PDGF-BB-induced DNA synthesis in VSMCs.

PMID- 10928959
TI  - Mechanism of terfenadine block of ATP-sensitive K(+) channels.
AB  - The ATP-sensitive K(+) (K(ATP)) channel is a complex of a pore-forming inwardly
      rectifying K(+) channel (Kir6.2) and a sulphonylurea receptor (SUR). The aim of
      the present study was to gain further insight into the mechanism of block of
      K(ATP) channels by terfenadine. Channel activity was recorded both from native
      K(ATP) channels from the clonal insulinoma cell line RINm5F and from a C-terminal
      truncated form of Kir6.2 (Kir6.2Delta26), which - in contrast to Kir6.2 -
      expresses independently of SUR. Kir6.2Delta26 channels were expressed in COS-7
      cells, and enhanced green fluorescent protein (EGFP) cDNA was used as a reporter
      gene. EGFP fluorescence was visualized by a laser scanning confocal microscope.
      Terfenadine applied to the cytoplasmic side of inside-out membrane patches
      concentration-dependently blocked both native K(ATP) channel and Kir6.2Delta26
      channel activity, and the following values were calculated for IC(50) (the
      terfenadine concentration causing half-maximal inhibition) and n (the Hill
      coefficient): 1.2 microM and 0.7 for native K(ATP) channels, 3.0 microM and 1.0
      for Kir6. 2Delta26 channels. Terfenadine had no effect on slope conductance of
      either native K(ATP) channels or Kir6.2Delta26 channels. Intraburst kinetics of
      Kir6.2Delta26 channels were not markedly affected by terfenadine and, therefore,
      terfenadine acts as a slow channel blocker on Kir6.2Delta26 channels. Terfenadine
      induced block of Kir6. 2Delta26 channels demonstrated no marked voltage
      dependence, and lowering the intracellular pH to 6.5 potentiated the inhibition
      of Kir6.2Delta26 channels by terfenadine. These observations indicate that
      terfenadine blocks pancreatic B-cell K(ATP) channels via binding to the
      cytoplasmic side of the pore-forming subunit. The presence of the pancreatic SUR1
      has a small, but significant enhancing effect on the potency of terfenadine.

PMID- 10928960
TI  - Selective modifiers of glutathione biosynthesis and 'repriming' of vascular
      smooth muscle photorelaxation.
AB  - Photorelaxation of vascular smooth muscle (VSM) is caused by the release of
      nitric oxide (NO) from a finite molecular store that can be depleted by
      irradiating pre-contracted arteries with visible light. The ability of an
      'exhausted' vessel to respond to a further period of illumination is lost
      temporarily but then recovers slowly as the photosensitive store is reconstituted
      in the dark. The recovery process, termed repriming, displays an absolute
      requirement for endothelium-derived NO and is inhibited by pre-treating arteries
      with ethacrynic acid, a thiol-alkylating agent. Here we demonstrate that agents
      that up- or down-regulate glutathione (GSH) biosynthesis influence the extent to
      which the store is regenerated in the dark. Isolated rat tail arteries (RTAs)
      were perfused internally with Krebs solution containing phenylephrine (PE; mean
      [PE] +/- s.e.mean: 5. 78+/-0.46 microM) and periodically exposed to laser light
      (lambda=514.5 nm, 6.3 mW cm(-2) for 6 min). Photorelaxations of control RTAs were
      compared with those from either (a) vessels taken from animals previously
      injected i.p. with buthionine sulphoximine (BSO), an inhibitor of gamma
      glutamylcysteine synthetase (three injections, 100 mg kg(-1) at 8 h intervals);
      or (b) isolated RTAs that were perfused ex vivo with oxothiazolidine (OXO), a
      precursor of cysteine (10(-4) M OXO for 60 min). RTAs from BSO-treated animals
      exhibited attenuated photorelaxations: the mean (+/-s.e.mean) amplitude of the
      response recorded after 72 min recovery in the dark was 12.4+/-1.6% versus 21.4+/
      2.9% for control arteries (n=5; P<0. 01). Conversely RTAs treated with OXO and
      allowed to recover for a similar period showed enhanced photorelaxations, 32.6+/
      6.3% as compared to 21.4+/-2.9% for control arteries (n=5; P<0.01). A hyperbolic
      curve fit to repriming curves for BSO-treated and control arteries returned
      asymptote values (maximum photorelaxations) of (mean +/- s.e.mean) 24.2+/-3.2%
      and 55.2+/-8.5%, respectively. The level of GSH in RTA extracts was measured by
      high-pressure liquid chromatography (HPLC). Injecting animals with BSO decreased
      GSH to 85% of control levels (P<0.05) while treatment of isolated vessels with
      OXO resulted in a 31% increase above control levels (P<0.05). Thus, drug-induced
      changes in RTA GSH levels were positively correlated with altered
      photorelaxations. The results lead us to postulate that the photosensitive store
      in VSM is generated, at least in part, from intracellular GSH which becomes
      converted to S-nitrosoglutathione (GSNO) by nitrosating species that are formed
      ultimately from endothelium-derived NO. The possible physiological significance
      of a photolabile store of NO in VSM is discussed briefly.

PMID- 10928962
TI  - A comparative study of the ability of calcitonin gene-related peptide and
      adrenomedullin(13 - 52) to modulate microvascular but not thermal hyperalgesia
      responses.
AB  - Calcitonin gene-related peptide (CGRP), a neuropeptide, is a potent vasodilator.
      Adrenomedullin (ADM) is suggested to be produced by vascular cells in inflamed
      tissue. ADM shares some structural homology with CGRP. We have compared the
      ability of CGRP and ADM to modulate microvascular and thermal hyperalgesic
      responses in rat skin. Vasodilator activity was assessed by laser Doppler
      flowmetry, inflammatory oedema by the extravascular accumulation of intravenously
      injected labelled albumin, and neutrophil accumulation by tissue myeloperoxidase,
      in dorsal skin. Hyperalgesia was assessed by a thermal hyperalgesimeter in paw
      skin. ADM (10-300 pmol) was 3 fold less potent than CGRP (3-100 pmol) as a direct
      vasodilator. CGRP (30 pmol) potentiated oedema formation induced by mediators of
      increased microvascular permeability, as expected (P<0.01). However, ADM (30-100
      pmol) was without a potentiating effect, although ADM (300 pmol) was effective
      (P<0.01). By comparison ADM (100 pmol) potentiated neutrophil accumulation
      induced by interleukin-1beta (P<0.05), whereas CGRP (30 pmol) did not. No thermal
      hyperalgesia was observed to either CGRP or ADM, when given as single or repeated
      treatments. Thus despite a dilator activity neither CGRP nor ADM appears to
      mediate hyperalgesic activity in the periphery. However ADM, like CGRP, has the
      ability to potentiate inflammatory oedema formation and, in addition, ADM can
      potentiate neutrophil accumulation. ADM may, as suggested for CGRP, act as a
      modulator of the vascular phases of inflammation. The property of the two
      compounds of evoking differential microvascular responses and neutrophil
      accumulation may be due to differing mechanisms of action.

PMID- 10928961
TI  - Abrogation of lung inflammation in sensitized Stat6-deficient mice is dependent
      on the allergen inhalation procedure.
AB  - Conflicting results have been reported about the role of Stat6 in allergen
      induced airway inflammation. We have studied the influence of the allergen
      inhalation procedure on the inflammatory response using wild-type and Stat6
      deficient mice generated on a C57BL/6 background. Animals were immunized i.p. on
      day 0 and 7 with ovalbumin (OVA) and then received aerosolized OVA or phosphate
      buffer saline challenge (acute on day 14; chronic on day 14, 15, 16, 17 and 18)
      before being sacrificed at different time points. Following an acute challenge,
      Stat6-deficiency fully abrogated the increase in serum IgE levels and the
      development of lung inflammation (inflammatory cell infiltration, IL-4 and IL-5
      release, and increase in plasma leakage). Following chronic challenge, despite
      the absence of IgE, IL-4 and IL-5, Stat6-deficient mice develop a characteristic
      lung inflammation, although the intensity was smaller when compared with the wild
      type mice. OVA-induced early bronchoconstriction was observed in wild-type mice
      only after chronic challenge, and this was totally abrogated in the Stat6
      deficient animals. These results suggest that Stat6 signalling is essential for
      the development of allergic airway inflammation following an acute allergen
      exposure. However, in a more chronic situation, the airway inflammatory response
      seems to be only partially mediated by Stat6.

PMID- 10928963
TI  - Characterization of [(125)I]-SB-258585 binding to human recombinant and native 5
      HT(6) receptors in rat, pig and human brain tissue.
AB  - SB-258585 (4-Iodo-N-[4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-benzen
      esulphonamide) is a high affinity ligand at 5-HT(6) receptors. It displays over
      100 fold selectivity for the 5-HT(6) receptor over all other 5-HT receptors
      tested so far. SB-258585 has been radiolabelled, to high specific activity, for
      its characterization as a 5-HT(6) receptor selective radioligand. [(125)I]-SB
      258585 bound, with high affinity, to a single population of receptors in a cell
      line expressing human recombinant 5-HT(6) receptors. Kinetic and saturation
      binding experiments gave pK(D) values of 9.01+/-0.09 and 9.09+/-0.02,
      respectively. In membranes derived from rat or pig striatum and human caudate
      putamen, [(125)I]-SB-258585 labelled a single site with high levels (>60%) of
      specific binding. Saturation analysis revealed pK(D) values of 8.56+/-0.07 for
      rat, 8.60+/-0.10 for pig and 8.90+/-0.02 for human. B(max) values for the tissues
      ranged from 173+/-23 and 181+/-25 fmol mg(-1) protein in rat and pig striatum,
      respectively, to 215+/-41 fmol mg(-1) protein in human caudate putamen. The pK(i)
      rank order of potency for a number of compounds, determined in competition
      binding assays with [(125)I]-SB-258585, at human caudate putamen membranes was:
      SB-271046>SB-258585>SB-214111>methiothepin>clozapine>5-Me-OT>5-HT>Ro 04
      6790>mianserin>ritanserin=amitriptyline>5-CT>mesulergine. Similar profiles were
      obtained from pig and rat striatal membranes and recombinant 5-HT(6) receptors;
      data from the latter correlated well with [(3)H]-LSD binding. Thus, [(125)I]-SB
      258585 is a high affinity, selective radioligand which can be used to label both
      recombinant and native 5-HT(6) receptors and will facilitate further
      characterization of this receptor subtype in animal and human tissues.

PMID- 10928964
TI  - Characterization of SB-271046: a potent, selective and orally active 5-HT(6)
      receptor antagonist.
AB  - SB-271046, potently displaced [(3)H]-LSD and [(125)I]-SB-258585 from human 5
      HT(6) receptors recombinantly expressed in HeLa cells in vitro (pK(i) 8.92 and
      9.09 respectively). SB-271046 also displaced [(125)I]-SB-258585 from human
      caudate putamen and rat and pig striatum membranes (pK(i) 8.81, 9.02 and 8.55
      respectively). SB-271046 was over 200 fold selective for the 5-HT(6) receptor vs.
      55 other receptors, binding sites and ion channels. In functional studies on
      human 5-HT(6) receptors SB-271046 competitively antagonized 5-HT-induced
      stimulation of adenylyl cyclase activity with a pA(2) of 8.71. SB-271046 produced
      an increase in seizure threshold over a wide-dose range in the rat maximal
      electroshock seizure threshold (MEST) test, with a minimum effective dose of < or
      =0.1 mg kg(-1) p.o. and maximum effect at 4 h post-dose. The level of
      anticonvulsant activity achieved correlated well with the blood concentrations of
      SB-271046 (EC(50) of 0.16 microM) and brain concentrations of 0.01-0.04 microM at
      C(max). These data, together with the observed anticonvulsant activity of other
      selective 5-HT(6) receptor antagonists, SB-258510 (10 mg kg(-1), 2-6 h pre-test)
      and Ro 04-6790 (1-30 mg kg(-1), 1 h pre-test), in the rat MEST test, suggest that
      the anticonvulsant properties of SB-271046 are likely to be mediated by 5-HT(6)
      receptors. Overall, these studies demonstrate that SB-271046 is a potent and
      selective 5-HT(6) receptor antagonist and is orally active in the rat MEST test.
      SB-271046 represents a valuable tool for evaluating the in vivo central function
      of 5-HT(6) receptors.

PMID- 10928965
TI  - Novel proline endopeptidase inhibitors do not modify Abeta40/42 formation and
      degradation by human cells expressing wild-type and swedish mutated beta-amyloid
      precursor protein.
AB  - Previous studies have suggested that proline endopeptidase (PE) could participate
      to the catabolism of the beta-amyloid peptide (Abeta) or to the
      physiopathological maturation of the beta-amyloid protein precursor (betaAPP). We
      have examined the putative ability of human purified PE to catabolize Abeta40 and
      Abeta42 and the possible contribution of this enzyme to the generation of Abeta40
      and Abeta42 in human HEK293 cells. We show first that purified human PE does not
      degrade synthetic Abeta40 and Abeta42, in vitro. We establish that HEK293 cell
      homogenates exhibit a Z-Gly-Pro-7AMC-cleaving enzyme, the activity of which is
      inhibited by Z-Pro-Prolinal and S17092 and S19825, two novel PE inhibitors, with
      affinities similar to those displayed on the purified human PE. These inhibitors
      also penetrate cells and achieve a full inhibition of endogenous proline
      endopeptidase in human cells. By means of selective antibodies directed towards
      the C-terminal of Abeta40 and Abeta42, we assessed the effect of PE inhibitors on
      the recovery of both Abeta species. This was examined in HEK293 cells stably
      overexpressing the wild-type and the familial Alzheimer's disease-related Swedish
      mutated beta-APP. We establish that none of these inhibitors affected Abeta40 or
      Abeta42 production in these transfected cells. Overall, our study indicates that
      human PE does not degrade Abeta40 and Abeta42. Furthermore, PE does not
      contribute to Abeta40 and Abeta42 formation in HEK293 cells. Therefore, PE does
      not appear to contribute to the Abeta-related aetiology of Alzheimer's disease.

PMID- 10928966
TI  - Structural factors that determine the ability of adenosine and related compounds
      to activate the cardiac ryanodine receptor.
AB  - The effects of adenosine and adenine on the gating of native sheep cardiac
      ryanodine receptor (RyR) channels were investigated. By examining the mechanisms
      underlying channel activation and by using comparative molecular field analysis
      (CoMFA) we have investigated the structural features of adenine-based ligands
      involved in channel activation. In the presence of 10 microM cytosolic Ca(2+),
      adenosine and adenine both activate the channel but only to a level approximately
      10 and 20% respectively of that of ATP indicating that both are partial agonists
      of low efficacy. Adenosine was able to antagonize the ATP-induced increase in
      open probability (Po) as expected for a partial agonist of low efficacy at the
      ATP sites on the cardiac RyR. GTP (100 microM - 10 mM) had no effect on channel
      gating indicating that the adenine ring structure is important for agonist
      activity at the ATP-sites on RyR. CoMFA revealed an extremely strong correlation
      between the structural features of the five ATP analogues and the ability to
      increase (Po). Our model indicates that the high efficacy of ATP results
      primarily from the large electrostatic field established by the ionized phosphate
      groups. Reducing the number of phosphate groups lowers the strength of this
      field, leading to ligands with lower efficacy. In addition, steric interactions
      between the alpha-phosphate and ribose moieties and the RyR are correlated with
      low Po.

PMID- 10928967
TI  - Evidence that adenosine 5'-triphosphate is the third inhibitory non-adrenergic
      non-cholinergic neurotransmitter in the rat gastric fundus.
AB  - In the rat gastric fundus, non-adrenergic, non-cholinergic (NANC) relaxations are
      mediated by nitric oxide (NO), vasoactive intestinal polypeptide (VIP), and a
      third, as yet unidentified, neurotransmitter. The possible involvement of
      adenosine 5'-triphosphate (ATP) in the NANC relaxations was examined using
      pyridoxalphosphate-6-azophenyl-2',5'-disulphonic acid (PPADS), apamin and
      desensitization to alpha,beta-methylene ATP. NANC responses were studied in the
      absence and presence of N(G)-nitro-L-arginine methyl ester (NAME; 100 microM) and
      alpha-chymotrypsin (1 u ml(-1)), to inhibit responses to NO and VIP,
      respectively. PPADS (100 microM), apamin (1 microM) and desensitization to
      alpha,beta-methylene ATP (10 microM, three additions) all significantly (P<0.05)
      reduced NANC relaxations to electrical field stimulation (0.5 - 4 Hz, 30 s
      trains) in longitudinal strips of rat gastric fundus and almost abolished the
      residual relaxation remaining in the presence of NAME and alpha-chymotrypsin.
      PPADS had no effect on responses to the NO-donor, sodium nitroprusside (SNP), or
      VIP. Apamin slightly reduced relaxations to SNP, but did not affect those to VIP,
      whereas desensitization to alpha,beta-methylene ATP markedly reduced responses to
      both SNP and VIP. The effects of PPADS and apamin in this study provide strong
      evidence that the third inhibitory NANC neurotransmitter in the rat gastric
      fundus is ATP.

PMID- 10928968
TI  - The P(2)-purinoceptor antagonist suramin is a competitive antagonist at
      vasoactive intestinal peptide receptors in the rat gastric fundus.
AB  - The P(2)-purinoceptor antagonist, suramin, was used to investigate the possible
      involvement of adenosine 5'-triphosphate (ATP) in the inhibitory non-adrenergic
      non-cholinergic (NANC) innervation of the rat gastric fundus. ATP (1-30 microM)
      produced biphasic responses consisting of concentration-dependent relaxations
      followed by concentration-dependent contractions. Suramin (200 microM)
      significantly reduced relaxations and abolished contractions to ATP. Under NANC
      conditions, electrical field stimulation (EFS) induced frequency-dependent
      relaxations. Suramin (200 microM) and the peptidase alpha-chymotrypsin (1 u ml(
      1)) had the same effects on EFS-induced relaxations: their duration was reduced,
      but their magnitude was unaffected. Cumulative relaxations to vasoactive
      intestinal peptide (VIP; 0.1-100 nM), and to the VIP analogue pituitary adenylate
      cyclase activating peptide 1-27 (PACAP; 0.2-100 nM), were almost completely
      abolished by alpha-chymotrypsin (1 u ml(-1)), and were inhibited by suramin (3
      200 microM) in an apparently competitive manner. Schild plot analysis indicated
      that suramin had pA(2) values of 5.1+/-0.2 (Hill slope=0.9+/-0.2) and 5.6+/-0.1
      (Hill slope=1.0+/-0.1), against VIP and PACAP, respectively. Concentration
      dependent relaxations to nitric oxide (1-30 microM) and cumulative relaxations to
      isoprenaline (0.1-300 nM) were not affected by suramin (200 microM). No
      conclusions can be made regarding the possible involvement of ATP in EFS-induced
      NANC relaxations. The results suggest that suramin acts as a competitive
      antagonist at VIP receptors in the rat gastric fundus.

PMID- 10928969
TI  - Orphanin FQ/nociceptin and [Phe(1)Psi(CH(2)-NH)Gly(2)] nociceptin(1-13)-NH(2)
      stimulate gastric motor function in anaesthetized rats.
AB  - Orphanin FQ/nociceptin (OFQ/N) is a preferred endogenous ligand for the orphan
      opioid receptor-like-1 receptor. This peptide has been reported to increase
      intestinal, but not gastric, motor activity. In the present study, OFQ/N (0.6-60
      nmol kg(-1) i.v.) increased intragastric pressure and antral contractility and,
      as expected, decreased blood pressure in anaesthetized rats. The gastric motor
      effects of OFQ/N (6 nmol kg(-1)) were not affected by inhibition of nitric oxide
      synthase or opioid receptor blockade. OFQ/N (6 nmol kg(-1)) evoked gastric motor
      increases and hypotension were not affected by prior administration of its
      derivative [Phe(1)Psi(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) unless the
      pseudopepotide was administered shortly (5 min) prior to OFQ/N. This putative
      antagonist (6-300 nmol kg(-1)) alone increased antral motility with approximately
      100 fold lower potency than OFQ/N. Neither bilateral vagotomy nor spinal cord
      transection altered OFQ/N-evoked increases in intragastric pressure and antral
      contractility. In conclusion, OFQ/N induces gastric motor excitation in addition
      to its known effects to increase intestinal motility. The gastric responses to
      OFQ/N are not dependent on 'classical' opioid receptor activation or nitric
      oxide, similar to the case for the intestines. The primary site of action of
      OFQ/N on the stomach is probably via enteric nerves, since central descending
      vagal or sympathetic pathways are not necessary for OFQ/N to increase gastric
      motility. The gastric motor effects of the derivative [Phe(1)Psi(CH(2)
      NH)Gly(2)]nociceptin-(1-13)-NH(2) are similar to OFQ/N, although with lower
      potency. The effects of the derivative as a partial agonist or antagonist in
      different experimental paradigms may reflect tissue OFQ/N receptor reserve.

PMID- 10928970
TI  - Involvement of interleukin-1 in the inflammatory actions of aminobisphosphonates
      in mice.
AB  - Aminobisphosphonates (aminoBPs) are potent inhibitors of bone resorption.
      However, they cause undesirable inflammatory reactions, including fever, in
      humans. Intraperitoneal injection of aminoBPs into mice also induces inflammatory
      reactions, including a prolonged elevation of the activity of the histamine
      forming enzyme, histidine decarboxylase (HDC). Because interleukin-1 (IL-1) is a
      typical pyrogen and a strong inducer of HDC, we examined whether aminoBPs induce
      inflammatory reactions in mice deficient in genes for both IL-1alpha and IL-1beta
      (IL-1-KO mice). In control mice, aminoBPs induced an elevation of HDC activity
      and other inflammatory reactions (enlargement of the spleen, atrophy of the
      thymus, exudate in the thorax and increase in granulocytic cells in the
      peritoneal cavity). These responses were all weak or undetectable in IL-1-KO
      mice. We have previously shown that lipopolysaccharides (LPSs) from Escherichia
      coli and Prevotella intermedia (a prevalent gram-negative bacterium both in
      periodontitis and endodontal infections) are capable of inducing HDC activity in
      various tissues in mice. In control mice treated with an aminoBP, the LPS-induced
      elevations of serum IL-1 (alpha and beta) and tissue HDC activity were both
      markedly augmented. However, such an augmentation of HDC activity was small or
      undetectable in IL-1-KO mice. These results, taken together with our previous
      findings (i) suggest that IL-1 is involved in the aminoBP-induced inflammatory
      reactions and (ii) lead us to think that under some conditions, inflammatory
      reactions induced by gram-negative bacteria might be augmented in patients
      treated with an aminoBP. In this study, we also obtained a result suggesting that
      IL-1-deficiency might be compensated by a second, unidentified, mechanism serving
      to induce HDC in response to LPS when IL-1 is lacking.

PMID- 10928971
TI  - FK506 potently inhibits T cell activation induced TNF-alpha and IL-1beta
      production in vitro by human peripheral blood mononuclear cells.
AB  - The aim of this study was to elucidate the in vitro inhibitory potency of FK506
      on production of the inflammatory cytokines, tumour necrosis factor (TNF)-alpha
      and interleukin (IL)-1beta, with a view to assessing this immunosuppressive agent
      as a potential anti-rheumatic drug. We employed an in vitro model which produces
      TNF-alpha and IL-1beta through T cell activation. Human peripheral blood
      mononuclear cells (PBMC) were cultured with immobilized anti-CD3/CD28 monoclonal
      antibody in this model. FK506 inhibited anti-CD3/CD28 induced TNF-alpha and IL
      1beta production at concentrations less than 1 ng ml(-1). Flow cytometric
      analysis of intracellular TNF-alpha and IL-1beta positive cells showed that FK506
      potently suppresses inflammatory cytokine production from CD14+ monocytes as well
      as from T cells. Cyclosporin A (CsA) and dexamethasone (DEX) also inhibited the
      anti-CD3/CD28 induced cytokine production, but were less potent than FK506. FK506
      and CsA, but not DEX, specifically inhibited anti-CD3/CD28 induced inflammatory
      cytokine production without affecting the lipopolysaccaride (LPS) induced effect.
      Methotrexate (MTX) was completely inactive for suppressing cytokine production
      under either condition. Anti-CD3/CD28 stimulated PBMC culture supernatants were
      found to enhance the expression of adhesion molecules in human vascular
      endothelial cells. FK506, CsA and DEX led to the suppression of adhesion molecule
      expression probably by inhibiting cytokine production from PBMC. The inhibitory
      potency of agents on TNF-alpha and IL-1beta production was compared with
      cytotoxicity and FK506 was not cytotoxic at concentrations several orders of
      magnitude greater than those required for cytokine inhibition. These results
      strongly suggest that FK506 may be most effective to specifically prevent T cell
      activation mediated inflammatory cytokine production in a clinical setting.

PMID- 10928972
TI  - Pharmacological characterization of metabotropic glutamate receptor-mediated high
      affinity GTPase activity in rat cerebral cortical membranes.
AB  - Activation of heterotrimeric guanine nucleotide-binding regulatory proteins (G
      proteins) functionally coupled to metabotropic glutamate receptors (mGluRs) was
      assessed by agonist-induced high-affinity GTPase (EC3.6.1.-) activity in rat
      cerebral cortical membranes. L-Glutamate (1 mM) stimulated high-affinity GTPase
      activity to the same extent throughout the incubation period up to 20 min, in a
      Mg(2+)-dependent manner. The addition of 1 mM L-glutamate augmented V(max) of the
      enzyme activity (1670 to 3850 pmol mg(-1) protein 15 min(-1)) with slight
      increase in K(M) value (0.26 to 0.63 microM). The high-affinity GTPase activity
      was stimulated by the following compounds with a rank order of potency of
      (2S,2'R,3'R)-2-(2', 3'-dicarboxycyclopropyl) glycine (DCG-IV) > (2S,1'S, 2'S)-2
      (carboxycyclopyropyl)glycine (L-CCG-I) > L-glutamate > or = 2R, 4R-4
      aminopyrrolidine-2,4-dicarboxylate [(2R,4R)-APDC] > 1S, 3R-1-aminocyclopentane
      1,3-dicarboxylate [(1S,3R)-ACPD] > (S)-4-carboxy-3-hydroxyphenylglycine [(S)
      4C3HPG] > (S)-3-carboxy-4-hydroxyphenylglycine [(S)-3C4HPG] > ibotenate, but not
      by L-(+)-2-amino-4-phosphonobutyrate (L-AP4), (RS)-3, 5-dihydroxyphenylglycine
      [(RS)-3,5-DHPG], quisqualate, or L-serine-O-phosphate (L-SOP), indicative of
      involvement of group II mGluRs, in particular mGluR2. (2S)-alpha-Ethylglutamate
      (EGLU), a presumably selective antagonist against group II mGluRs, inhibited DCG
      IV-stimulated high-affinity GTPase activity in a competitive manner with an
      apparent K(B) of 220 microM. L-Glutamate-stimulated activity was eliminated by
      pretreatment of the membranes with sulfhydryl alkylating agent N-ethylmaleimide
      (NEM) at 30-50 microM, indicating that G-proteins of the G(i) family are
      involved. These results indicate that mGluR agonist-induced high-affinity GTPase
      activity in rat cerebral cortical membranes may be used to detect the functional
      interaction between group II mGluRs, in particular mGluR2, and NEM-sensitive G(i)
      proteins.

PMID- 10928973
TI  - Heart failure development in rats with ascending aortic constriction and
      angiotensin-converting enzyme inhibition.
AB  - It remains unknown whether angiotensin-converting enzyme (ACE) inhibition can
      prevent heart failure in rats with a fixed high pressure load of the left
      ventricle and if this effect could be attributed to normalization of contractile
      protein phenotype and cardiac collagen content. Rats with constriction of the
      ascending aorta were treated with the ACE inhibitor quinapril (6 mg kg(-1) day(
      1)) (n=95) or placebo (n=96) (starting 6 weeks post surgery. Quinapril treatment
      improved survival markedly (P<0.0000001) during the 24 weeks observation period.
      There were 69 deaths with placebo and only 25 deaths with quinapril. At the end
      of the observation period signs of left ventricular backward failure were,
      however, detected in 75 rats with placebo and in 67 rats treated with quinapril
      (P=0.229). Cox proportional hazard model with time-dependent covariates was used
      to document that the effect of quinapril treatment had been dependent on time.
      Quinapril had no significant effect on the development of morphological signs of
      left ventricular dysfunction after the first 54 days of treatment. The increased
      isomysin V(3) proportion of hypertrophied non-failing hearts was also not
      affected by quinapril treatment. Irrespective of treatment, failing hypertrophied
      hearts were characterized by an increase in left ventricular volume (P<0.05),
      percentage of the 'foetal' isomyosin V(3) (P<0.05), and hydroxyproline
      concentration (P<0.05). While the cause of the improved survival remains unknown,
      quinapril did apparently not interfere with the restitution of 'foetal' gene
      expression of pressure overloaded cardiomyocytes leading to depressed myocardial
      performance, ventricular dysfunction and the consecutive myocardial fibrosis.

PMID- 10928974
TI  - Sulphonylurea drugs reduce hypoxic damage in the isolated perfused rat kidney.
AB  - Sulphonylurea drugs have been shown to protect against hypoxic damage in isolated
      proximal tubules of the kidney. In the present study we investigated whether
      these drugs can protect against hypoxic damage in a whole kidney preparation.
      Tolbutamide (200 microM) and glibenclamide (10 microM) were applied to the
      isolated perfused rat kidney prior to changing the gassing from oxygen to
      nitrogen for 30 min. Hypoxic perfusions resulted in an increased fractional
      excretion of glucose (FE % glucose 14.3+/-1.5 for hypoxic perfusions vs 4.9+/-1.6
      for normoxic perfusions, mean +/- s.e. mean, P<0.05), which could be completely
      restored by 200 microM tolbutamide (5.7+/-0.4 for tolbutamide vs 14.3+/-1.5 for
      untreated hypoxic kidneys, P<0.01). Furthermore, tolbutamide reduced the total
      amount of LDH excreted in the urine (220+/-100 mU for tolbutamide vs. 1220+/-160
      mU for untreated hypoxic kidneys, P<0.01). Comparable results were obtained with
      glibenclamide (10 microM). In agreement with the effect on functional parameters,
      ultrastructural analysis of proximal tubules showed increased brush border
      preservation in tolbutamide treated kidneys compared to untreated hypoxic
      kidneys. We conclude that glibenclamide and tolbutamide are both able to reduce
      hypoxic damage to proximal tubules in the isolated perfused rat kidney when
      applied in the appropriate concentrations.

PMID- 10928975
TI  - Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have
      different subtypes of alpha(1) adrenoceptors.
AB  - Neurally evoked contractions and release of (3)H- acetylcholine (ACh) during
      electrical field stimulation were measured in rat urinary bladder strips. The
      alpha(1) agonist phenylephrine (PE, 2-8 microM) increased the amplitude of
      neurally evoked contractions, facilitated the release of ACh and increased the
      baseline tone of the bladder strips. The PE-induced facilitation of the
      contractions did not significantly change during a prolonged exposure to PE (120
      min), whereas the PE-induced rise in baseline tone gradually decreased to 65% of
      the initial value. Low concentrations of specific alpha(1A) antagonists, 5-methyl
      urapidil (5-MU), REC15/2739 and WB-4101 competitively inhibited the facilitation
      of the neurally-evoked contractions (pA(2:) 8.77; 9.59 and 9.62, respectively),
      whereas higher concentrations of 5-MU (IC(50): 48 nM) were required to suppress
      the PE-rise in baseline. WB-4101 (100 microM) inhibited the PE-induced
      facilitation of ACh release. The irreversible alpha(1B) antagonist chloroethyl
      clonidine (CEC, 10-50 microM) inhibited the PE-evoked rise in base line tone, but
      did not affect the PE-induced facilitation of the neurally evoked contractions
      nor the facilitation of ACh release. However, CEC increased the area and
      amplitude of the neurally-evoked contractions by 261+/-33 and 47.2+/-8.4%,
      respectively. Atropine significantly inhibited the CEC evoked increase in area
      and amplitude of the electrically evoked contractions (76.5+/-4.8 and 40.8+/-3%,
      respectively) indicating that CEC facilitated the cholinergic responses of the
      electrically stimulated bladder strips. It is concluded that alpha(1A) and CEC
      sensitive alpha(1B) and/or alpha(1D) adrenoceptors are expressed in the rat
      bladder in different locations. On the cholinergic nerve terminals alpha(1A)
      adrenoceptors mediate prejunctional facilitation, whereas postjunctional
      alpha(1B)/alpha(1D) adrenoceptors mediate smooth muscle contraction.

PMID- 10928977
TI  - Effects of a selective neuropeptide Y Y(1) receptor antagonist BIBP 3226 on
      double peaked vasoconstrictor responses to periarterial nerve stimulation in
      canine splenic arteries.
AB  - The periarterial electrical nerve stimulation (30 s trains of pulses at a
      frequency of 1, 4 or 10 Hz) induced a double peaked vasoconstriction consisting
      of an initial transient constriction (first peak) followed by a prolonged
      response (second peak) in the isolated, perfused canine splenic artery. At low
      frequencies (1 and 4 Hz), a neuropeptide Y (NPY) Y(1) receptor antagonist BIBP
      3226 (0.1-1 microM) produced a dose-dependent inhibitory effect on the second
      peak, but did not modify the first peak. At a high frequency (10 Hz), 1 microM
      BIBP 3226 induced a slight, but significant inhibition on both the first and
      second peaked responses. At a low frequency (1 Hz), the first peak was not
      influenced by blockade of alpha(1)-adrenoceptors or NPY Y(1) receptors with
      prazosin (0.1 microM) or BIBP 3226 (1 microM), respectively, but abolished by P2X
      receptor desensitization with alpha,beta-methylene ATP (alphabeta-m ATP, 1
      microM). At a high frequency (10 Hz), the first peak was mostly inhibited by
      alphabeta-m ATP and partially by prazosin and BIBP 3226. On the other hand, the
      second peak at a low frequency was largely decreased by BIBP 3226 and partially
      by prazosin and alphabeta-m ATP, whereas at a high frequency, it was largely
      attenuated by prazosin and partially by alphabeta-m ATP and BIBP 3226. The
      results suggest that at a low frequency, the firstly transient constriction of
      double peaked responses is mainly induced via an activation of P2X-receptors,
      whereas at a high frequency, it is mostly mediated by the P2X-receptors, and
      partially by alpha(1)-receptors and NPY Y(1)-receptors. The secondary prolonged
      vasoconstriction at frequencies used is predominantly mediated via both alpha(1)
      receptor and NPY Y(1) receptor activations, and in part by P2X-receptors.
      Furthermore, an activation of NPY Y(1) receptors may play an important role in
      evoking the prolonged vasoconstrictor response to longer pulse trains of
      stimulation at a low frequency, whereas an alpha(1)-adrenoceptor activation
      exerts a main vasomotor effect for the prolonged response at a high frequency.

PMID- 10928976
TI  - Ketamine potentiates cerebrocortical damage induced by the common anaesthetic
      agent nitrous oxide in adult rats.
AB  - For general anaesthesia, patients usually receive a combination of drugs, all of
      which are classified as gamma-amino-butyric acid (GABA) agonists, with two
      notable exceptions - ketamine and nitrous oxide (laughing gas, N(2)O) - which are
      antagonists of N-methyl-D-aspartate (NMDA) glutamate receptors. At clinically
      relevant doses both ketamine and N(2)O, like other NMDA antagonists, have the
      potential to induce psychotomimetic reactions in humans and to cause
      pathomorphological changes in cerebrocortical neurons in rat brain. Because drug
      combinations used in clinical anaesthesia sometimes include both ketamine and
      N(2)O, we undertook experiments to evaluate whether augmented neurotoxicity
      results from their combined use. Ketamine and N(2)O were administered alone or in
      combination by various dosing regimens to adult female rats for a duration of 3 h
      and the severity of cerebrocortical neurotoxic changes was quantified
      histologically. Because GABA agonists are known to protect against the
      psychotomimetic and neurotoxic effects of NMDA antagonists, we also evaluated
      whether the combined neurotoxicity of ketamine+N(2)O can be prevented by certain
      commonly used GABA agonists. When ketamine and N(2)O were used in combination the
      neurotoxic reaction was enhanced to a degree much greater than can be explained
      by simple additivity. The apparent synergistic interaction was particularly
      striking when low doses of the agents were combined, the degree of toxic
      synergism at higher doses being masked by a ceiling effect. GABA agonists
      protected against ketamine/N(2)O neurotoxicity. It is recommended that this
      information be taken into consideration in the selection of drugs to be used in
      multi-agent protocols for general anaesthesia.

PMID- 10928978
TI  - Dual interaction of agmatine with the rat alpha(2D)-adrenoceptor: competitive
      antagonism and allosteric activation.
AB  - In segments of rat vena cava preincubated with [(3)H]-noradrenaline and
      superfused with physiological salt solution, the influence of agmatine on the
      electrically evoked [(3)H]-noradrenaline release, the EP(3) prostaglandin
      receptor-mediated and the alpha(2D)-adrenoceptor-mediated inhibition of evoked
      [(3)H]-noradrenaline release was investigated. Agmatine (0.1-10 microM) by itself
      was without effect on evoked [(3)H]-noradrenaline release. In the presence of 10
      microM agmatine, the prostaglandin E(2)(PGE(2))-induced EP(3)-receptor-mediated
      inhibition of [(3)H]-noradrenaline release was not modified, whereas the
      alpha(2D)-adrenoceptor-mediated inhibition of [(3)H]-noradrenaline release
      induced by noradrenaline, moxonidine or clonidine was more pronounced than in the
      absence of agmatine. However, 1 mM agmatine antagonized the moxonidine-induced
      inhibition of [(3)H]-noradrenaline release. Agmatine concentration-dependently
      inhibited the binding of [(3)H]-clonidine and [(3)H]-rauwolscine to rat brain
      cortex membranes (K(i) values 6 microM and 12 microM, respectively). In addition,
      30 and 100 microM agmatine increased the rate of association and decreased the
      rate of dissociation of [(3)H]-clonidine resulting in an increased affinity of
      the radioligand for the alpha(2D)-adrenoceptors. [(14)C]-agmatine labelled
      specific binding sites on rat brain cortex membranes. In competition experiments.
      [(14)C]-agmatine was inhibited from binding to its specific recognition sites by
      unlabelled agmatine, but not by rauwolscine and moxonidine. In conclusion, the
      present data indicate that agmatine both acts as an antagonist at the ligand
      recognition site of the alpha(2D)-adrenoceptor and enhances the effects of
      alpha(2)-adrenoceptor agonists probably by binding to an allosteric binding site
      of the alpha(2D)-adrenoceptor which seems to be labelled by [(14)C]-agmatine.

PMID- 10928980
TI  - Characterization of the effects of cannabinoids on guinea-pig tracheal smooth
      muscle tone: role in the modulation of acetylcholine release from parasympathetic
      nerves.
AB  - We investigated the ability of the cannabinoid agonists CP55,940 (CB(1)/CB(2))
      and anandamide (endogenous cannabinoid) to modulate electrical field stimulation
      (EFS)-induced acetylcholine (ACh) release from parasympathetic nerve terminals
      innervating guinea-pig trachea. We assessed whether modulation of transmitter
      release translated to an impact on functional responses by investigating the
      effect of these agents on contractile responses evoked by EFS and ACh.
      Furthermore, we evaluated the ability of these compounds to elicit
      bronchodilation in pre-contracted guinea-pig tracheal strips. CP55,940 and
      anandamide significantly inhibited EFS-evoked ACh release (maximal inhibition of
      35.1+/-2.9% and 33.4+/-6.4% at 1 microM, P<0.05, respectively). The CB(1)
      receptor antagonist SR 141716A (1 microM), had no effect on ACh release and
      failed to reverse the inhibitory effect of CP55,940 (1 microM). Paradoxically,
      CP55,940 had no significant effect on EFS-evoked cholinergic contractile
      responses. Furthermore, CP55,940 did not relax pre-contracted tracheal strips or
      affect contractile responses to exogenous ACh. This lack of activity on smooth
      muscle tone is consistent with the fact that no detectable specific binding of
      [(3)H] CP55,940 was found in tracheal homogenates. These data suggest that
      cannabinoid agonists inhibit ACh release from cholinergic nerve terminals via
      activation of CB(2) receptors but that this inhibitory action does not impact on
      functional responses such as cholinergic contraction.

PMID- 10928981
TI  - Yersinia enterocolitica invasin protein triggers IL-8 production in epithelial
      cells via activation of Rel p65-p65 homodimers.
AB  - Enteropathogenic Yersinia bacteria trigger the production of the proinflammatory
      chemokine IL-8, an important chemokine for the recruitment of polymorphonuclear
      leukocytes (PMN). Yersinia is resistant to phagocytosis by PMN, and the
      recruitment of these cells is thought to be part of a pathogenic strategy of
      Yersinia to establish infection by allowing the pathogen to gain access to, and
      disseminate within, host tissue. We report here that Yersinia expressing the
      outer membrane protein invasin triggers IL-8 production in epithelial cells. The
      195 carboxyl-terminal amino acids of invasin when linked to latex beads are
      sufficient to trigger IL-8 production. By means of IL-8 promoter reporter gene
      assays and electrophoretic mobility shift assay experiments, the minimal optimal
      region of the IL-8 promoter responsive to invasin was identified and invasin
      responsive control elements were characterized. Invasin-induced activation of the
      IL-8 promoter was found to be mediated through a previously identified NF-kappaB
      element. This NF-kappaB binding site preferentially binds Rel p65-p65 homodimers
      as well as some p50-p65 heterodimers in response to stimulation by invasin.
      Invasin-induced NF-kappaB activation correlated with degradation of IkappaBalpha
      and the inhibition of NF-kappaB by specific inhibitors of IkappaB activation
      blocked invasin-induced IL-8 secretion. Invasin-triggered IL-8 production does
      not depend on invasin-triggered uptake of bacteria, and is independent of a
      functional PI3-kinase. This report is the first to demonstrate the molecular
      basis of IL-8 production triggered by enteropathogenic bacteria. Together, these
      data elucidate the possible early pathomechanisms operating in Yersinia infection
      and may have implications for the design of novel therapeutics directed against
      this enteropathogen.

PMID- 10928979
TI  - Latency to paroxetine-induced anxiolysis in the rat is reduced by co
      administration of the 5-HT(1A) receptor antagonist WAY100635.
AB  - We report here the use of rat high-light social interaction to model the temporal
      anxiolytic/antidepressant effects of SSRIs seen in the clinic. Compared to
      vehicle controls, 21, but not 14, days of paroxetine treatment (3 mg kg(-1),
      p.o., daily) produced a marked increase in rat social interaction (Vehicle=71.3+/
      7.3 s; Paroxetine=116.7+/-14.7 s; P<0.01) with no concurrent effect on locomotor
      activity, consistent with anxiolysis. To assess whether concurrent 5-HT(1A)
      receptor blockade reduces the time to onset of anxiolysis seen with paroxetine
      alone (21 days), rats were implanted with osmotic minipumps to continuously
      infuse the 5-HT(1A) receptor antagonist WAY100635 (1 mg kg(-1) day(-1), s.c., 7
      days) alone or in combination with paroxetine (3 mg kg(-1), p.o., daily, 7 days),
      prior to anxiety testing. Paroxetine (Veh/Par=61.9+/-7.9 s) or WAY100635
      (WAY/Veh=71.6+/-4.7 s) alone, had no effect on social interaction time compared
      to vehicle treated controls (Veh/Veh=76.4+/-4.9 s), whilst coadministration of
      WAY100635 with paroxetine, produced a marked elevation in social interaction
      (WAY/Par=149.3+/-16.8 s; P<0.01) relative to all other groups with no concurrent
      change in locomotor activity. In contrast, acute administration of WAY100635
      (0.03 mg kg(-1), s.c.) with paroxetine (3 mg kg(-1), p.o.) did not alter any
      behavioural measure, suggesting that the anxiolysis induced by the combination
      after 7 days is attributable to a CNS adaptive response. This data demonstrates
      that coadministration of a 5-HT(1A) receptor antagonist with paroxetine markedly
      reduces the latency to anxiolysis, in the rat. This study supports the use of the
      rat social interaction test to further delineate adaptive changes in the CNS
      responsible for the anxiolytic/antidepressant action of SSRIs seen in humans.

PMID- 10928982
TI  - Subacute NO generation induced by Alzheimer's beta-amyloid in the living brain:
      reversal by inhibition of the inducible NO synthase.
AB  - Glial activation contiguous to deposits of amyloid peptide (Abeta) is a
      characteristic feature in Alzheimer's disease. We performed complementary in
      vitro and in vivo experiments to study the extent, kinetics, and mechanisms of
      microglial generation of nitric oxide (NO) induced by challenge with Abeta. We
      showed that Abeta fibrils dose-dependently induced a marked release of stable
      metabolites of NO in vivo that was strikingly similar regarding extent and
      temporal profile to the one in the parallel designed microglial cell culture
      experiments. However, costimulation with interferon gamma, which was a
      prerequisite for Abeta-induced NO generation in vitro, was not required in vivo,
      demonstrating that factors are present in the living brain that activate glial
      cells synergistically with Abeta. Therefore, in Alzheimer's disease, deposits of
      Abeta fibrils alone may be sufficient to induce a chronic release of neurotoxic
      microglial products, explaining the progressive neurodegeneration associated with
      this disease. Our observation that systemic administration of selective iNOS
      inhibitors abolishes Abeta-induced NO generation in vivo may have implications
      for therapy of Alzheimer's disease.

PMID- 10928983
TI  - Proteasome inhibition by lipofuscin/ceroid during postmitotic aging of
      fibroblasts.
AB  - We have studied the effects of hyperoxia and of cell loading with artificial
      lipofuscin or ceroid pigment on the postmitotic aging of human lung fibroblast
      cell cultures. Normobaric hyperoxia (40% oxygen) caused an irreversible
      senescence-like growth arrest after about 4 wk and shortened postmitotic life
      span from 1-1/2 years down to 3 months. During the first 8 wk of hyperoxia
      induced 'aging', overall protein degradation (breakdown of [(35)S]methionine
      metabolically radiolabeled cell proteins) increased somewhat, but by 12 wk and
      thereafter overall proteolysis was significantly depressed. In contrast, protein
      synthesis rates were unaffected by 12 wk of hyperoxia. Lysosomal cathepsin
      specific activity (using the fluorogenic substrate z-FR-MCA) and cytoplasmic
      proteasome-specific activity (measured with suc-LLVY-MCA) both declined by 80% or
      more over 12 wk. Hyperoxia also caused a remarkable increase in lipofuscin/ceroid
      formation and accumulation over 12 wk, as judged by both fluorescence
      measurements and FACscan methods. To test whether the association between
      lipofuscin/ceroid accumulation and decreased proteolysis might be causal, we next
      exposed cells to lipofuscin/ceroid loading under normoxic conditions.
      Lipofuscin/ceroid-loaded cells indeed exhibited a gradual decrease in overall
      protein degradation over 4 wk of treatment, whereas protein synthesis was
      unaffected. Proteasome specific activity decreased by 25% over this period, which
      is important since proteasome is normally responsible for degrading oxidized cell
      proteins. In contrast, an apparent increase in lysosomal cathepsin activity was
      actually caused by a large increase in the number of lysosomes per cell. To test
      whether lipofuscin/ceroid could in fact directly inhibit proteasome activity,
      thus causing oxidized proteins to accumulate, we incubated purified proteasome
      with lipofuscin/ceroid preparations in vitro. We found that proteasome is
      directly inhibited by lipofuscin/ceroid. Our results indicate that an
      accumulation of oxidized proteins (and lipids) such as lipofuscin/ceroid may
      actually cause further increases in damage accumulation during aging by
      inhibiting the proteasome.

PMID- 10928984
TI  - Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory
      cytokine IL-6: a general role for inflammation?
AB  - High levels of prostaglandins are produced in human oropharyngeal carcinoma
      (OPC). Five human OPC cell lines tested expressed both isoforms of
      cyclooxygenases (COX). The pan-COX inhibitor ketorolac continuously and
      significantly decreased PGE(2) production and IL-6 and IL-8 levels in all OPC
      cell lines tested, but did not affect IL-1alpha, GM-CSF levels, or in vitro tumor
      cell growth. In contrast, ketorolac reduced OPC growth in vivo. The OPC cell
      lines used express the IL-6 receptor, and IL-6 stimulation of these cells causes
      transduction to occur via STAT3 pathway activation. Coincubation with OPC cell
      lines with conditioned medium from a TPA-exposed HL-60 cells stimulated growth
      proportional to the IL-6 levels measured in the conditioned medium. This growth
      effect was specifically inhibited by anti-IL-6 antibody. These results are
      consistent with cytokine products of inflammatory cells having paracrine growth
      effects on OPC. If chronic inflammation plays a role in promoting the development
      of OPC, this mechanism may also apply to other epithelial tumor systems modulated
      by COX activity.

PMID- 10928985
TI  - Carboxyl-terminal fragment of Alzheimer's APP destabilizes calcium homeostasis
      and renders neuronal cells vulnerable to excitotoxicity.
AB  - Numerous lines of evidence indicate that some of the neurotoxicity associated
      with Alzheimer's disease (AD) is due to proteolytic fragments of the amyloid
      precursor protein (APP). Most research has focused on the amyloid beta peptide
      (Abeta). However, the possible role of other cleaved products of APP is less
      clear. We have previously shown that a recombinant carboxy-terminal 105 amino
      acid fragment (CT 105) of APP induced strong nonselective inward currents in
      Xenopus oocyte; it also revealed neurotoxicity in PC12 cells and primary cortical
      neurons, blocked later phase of long-term potentiation in rat hippocampus in
      vivo, and induced memory deficits and neuropathological changes in mice. We
      report here that the pretreatment with CT 105 for 24 h at a 10 microM
      concentration increases intracellular calcium concentration by about twofold in
      SK-N-SH and PC 12 cells, but not in U251 cells, originated from human
      glioblastoma. In addition, the calcium increase and toxicity induced by CT 105
      were reduced by cholesterol and MK 801 in SK-N-SH and PC 12 cells, whereas the
      toxicity of Abeta(1-42) was attenuated by nifedipine and verapamil. CT 105
      rendered SK-N-SH cells and rat primary cortical neurons more vulnerable to
      glutamate-induced excitotoxicity. Also, conformational studies using circular
      dichroism experiments showed that CT 105 has approximately 15% of beta-sheet
      content in phosphate buffer and aqueous 2,2, 2-trifluoroethanol solutions.
      However, the content of beta-sheet conformation in dodecyl phosphocholine micelle
      or in the negatively charged vesicles, is increased to 22%-23%. The results of
      this study showed that CT 105 disrupts calcium homeostasis and renders neuronal
      cells more vulnerable to glutamate-induced excitotoxicity, and that some portion
      of CT 105 has partial beta-sheet conformation in various environments, which may
      be related to the self-aggregation and toxicity. This may be significantly
      possibly involved in inducing the neurotoxicity characteristic of AD.

PMID- 10928986
TI  - Oxidative stress and expression of p22phox are involved in the up-regulation of
      tissue factor in vascular smooth muscle cells in response to activated platelets.
AB  - Vascular injury after balloon angioplasty results in the rapid activation of
      platelets leading to the release of growth factors and vasoactive substances. In
      addition, up-regulation of tissue factor (TF) and an increased production of
      reactive oxygen species (ROS) have been detected at sites of vascular injury. We
      investigated whether platelet-derived products (PDP) released from activated
      human platelets increase ROS production, resulting in the induction of TF
      expression in vascular smooth muscle cells (SMC). PDP induced a time- and
      concentration-dependent increase in ROS generation in cultured SMC that was
      mediated mainly by PDGF-AB and TGF-beta1 and impaired by the flavin inhibitor
      diphenylene iodonium. Increased ROS formation was associated with enhanced mRNA
      levels of the small NAD(P)H oxidase subunit p22phox or its smooth muscle isoform.
      Transient transfection with a p22phox antisense vector decreased PDP-induced ROS
      generation. PDP up-regulated TF mRNA expression, which was redox sensitive and
      reduced by transfection of the p22phox antisense vector. In addition, PDP
      stimulated reporter gene activity of two TF promoter constructs was decreased by
      coexpression of the p22phox antisense vector. These results indicate that
      activated platelets up-regulate TF expression and that this response involves ROS
      generation and a p22phox-containing NAD(P)H oxidase in SMC.

PMID- 10928987
TI  - Cell-penetrating SH3 domain blocker peptides inhibit proliferation of primary
      blast cells from CML patients.
AB  - Bcr-Abl contributes prominently to the development of most chronic myeloid
      leukemias (CMLs). Prior work has identified the adapter protein CRKL as a major
      substrate of the Bcr-Abl tyrosine kinase. CRKL can also bind via its first SH3
      domain [SH3(1)] to specific sequences in Bcr-Abl. Cell-penetrating peptides were
      developed that bind with high affinity and selectivity to the SH3(1) domain of
      CRKL. They disrupt Bcr-Abl-CRKL complexes and strongly reduce the proliferation
      of primary CML blast cells and cell lines established from Bcr-Abl-positive
      patients. Activation-specific antibodies against phosphorylated MAP kinase (MAPK)
      showed that MAPK activity is down-regulated in blast cells treated with the
      CRKLSH3(1) blocker peptides. We conclude that the Bcr-Abl-CRKL complexes are
      largely dependent on the CRKLSH3(1) domain, that the central mitogenic cascade is
      down-regulated as a consequence of the disruption of CRKLSH3(1) interactions, and
      that CRKL therefore contributes to the proliferation of CML blast cells.

PMID- 10928988
TI  - MSH4 acts in conjunction with MLH1 during mammalian meiosis.
AB  - MSH4 is a meiosis-specific MutS homolog. In yeast, it is required for reciprocal
      recombination and proper segregation of homologous chromosomes at meiosis I. MLH1
      (MutL homolog 1) facilitates both mismatch repair and crossing over during
      meiosis in yeast. Germ-line mutations in the MLH1 human gene are responsible for
      hereditary nonpolyposis cancer, but the analysis of MLH1-deficient mice has
      revealed that MLH1 is also required for reciprocal recombination in mammals. Here
      we show that hMSH4 interacts with hMLH1. The two proteins are
      coimmunoprecipitated regardless of the presence of DNA or ATP, suggesting that
      the interaction does not require the binding of MSH4 to DNA. The domain of hMSH4
      responsible for the interaction is in the amino-terminal part of the protein
      whereas the region that contains the ATP binding site and helix-turn-helix motif
      does not bind to hMLH1. Immunolocalization analysis shows that MSH4 is present at
      sites along the synaptonemal complex as soon as homologous chromosomes synapse.
      The number of MSH4 foci decreases gradually as pachynema progresses. During this
      transition, MLH1 foci begin to appear and colocalize with MSH4. These results
      suggest that MSH4 is first required for chromosome synapsis and that this MutS
      homologue is involved later with MLH1 in meiotic reciprocal recombination.

PMID- 10928989
TI  - Evaluation of alpha(1)-adrenoceptor antagonist on diabetes-induced changes in
      peripheral nerve function, metabolism, and antioxidative defense.
AB  - The role for nerve blood flow (NBF) vs. other factors in motor nerve conduction
      (MNC) slowing in short-term diabetes was assessed by evaluating alpha(1)
      adrenoceptor antagonist prazosin on NBF, MNC, as well as metabolic imbalances and
      oxidative stress in the neural tissue. Control and diabetic rats were treated
      with or without prazosin (5 mg.kg(-1).d(-1) for 3 wk). NBF was measured by
      hydrogen clearance. Both endoneurial vascular conductance and MNC velocity were
      decreased in diabetic rats vs. controls, and this decrease was prevented by
      prazosin. Free NAD(+):NADH ratios in mitochondrial cristae, matrix, and cytosol
      assessed by metabolite indicator method, as well as phosphocreatine levels and
      phosphocreatine/creatine ratios, were decreased in diabetic rats, and this
      reduction was ameliorated by prazosin. Neither diabetes-induced accumulation of
      two major glycation agents, glucose and fructose, as well as sorbitol and total
      malondialdehyde plus 4-hydroxyalkenals nor depletion of myo-inositol, GSH, and
      taurine or decrease in (Na/K)-ATP-ase activity were affected by prazosin. In
      conclusion, decreased NBF, but not metabolic imbalances or oxidative stress in
      the neural tissue, is a key mechanism of MNC slowing in short-term diabetes.
      Further experiments are needed to estimate whether preservation of NBF is
      sufficient for prevention of nerve dysfunction and morphological abnormalities in
      long-standing diabetes or whether the aforementioned metabolic imbalances closely
      associated with impaired neurotropism are of greater importance in advanced than
      in early diabetic neuropathy.

PMID- 10928990
TI  - A rab3 homolog in sea urchin functions in cell division.
AB  - Rabs are monomeric GTP binding proteins belonging to the ras superfamily that
      function throughout the secretory pathway. Members of the rab3 family function in
      the final steps of the secretory pathway, vesicle fusion with the plasma
      membrane. In contrast to mammalian systems with several rab3 isoforms (rab3A-D),
      a single family member homologue of rab3 is present in the rapidly dividing
      cleavage stage sea urchin embryo that localizes to numerous vesicles enriched at
      the cell cortex. We hypothesized that whereas the contents of these rab3-positive
      vesicles may contribute to the embryonic extracellular matrix, the membrane and
      its constituent proteins may be important for other aspects of cell division. We
      tested the function of rab3 in cell division by the microinjection of either
      antibodies or competing effector domain peptides to interfere with its function.
      We found that perturbing rab3 function results in cessation of cell division,
      whereas cells injected with either heat-inactivated antibodies or control
      scrambled peptides develop as normal. Moreover, neither endocytosis nor general
      membrane topology are affected by rab3 perturbation. Thus, we conclude that rab3
      associated vesicles and/or their contents are critical for cell division.

PMID- 10928991
TI  - Lipid hydroperoxide-induced apoptosis in human colonic CaCo-2 cells is associated
      with an early loss of cellular redox balance.
AB  - Apoptosis plays a critical role in maintaining homeostasis of the intestinal
      epithelium. Dietary oxidants like peroxidized lipids could perturb cellular redox
      status and disrupt mucosal turnover. The objective of this study was to delineate
      the role of lipid hydroperoxide (LOOH) -induced redox shifts in intestinal
      apoptosis using the human colonic CaCo-2 cell. We found that subtoxic
      concentrations of LOOH increased CaCo-2 cell apoptosis. This LOOH-induced
      apoptosis was associated with a significant decrease in the ratio of reduced
      glutathione-to-oxidized glutathione (GSH/GSSG), which preceded DNA fragmentation
      by 12 to 14 h, suggesting a temporal relationship between the two events.
      Oxidation of GSH with the thiol oxidant diamide caused significant decreases in
      cellular GSH and GSH/GSSG at 15 min that correlated with the activation of
      caspase 3 (60 min) and cleavage of PARP (120 min), confirming a temporal link
      between induction of cellular redox imbalance and initiation of apoptotic cell
      death. These kinetic studies further reveal that oxidant-mediated early redox
      change (within 1 h) was a primary inciting event of the apoptotic cascade. Once
      initiated, the recovery of redox balance did not prevent the progression of CaCo
      2 cell apoptosis to its biological end point at 24 h. Collectively, the study
      shows that subtoxic levels of LOOH disrupt intestinal redox homeostasis, which
      contributes to apoptosis. These results provide insights into the mechanism of
      hydroperoxide-induced mucosal turnover that have important implications for
      understanding oxidant-mediated genesis of gut pathology.

PMID- 10928992
TI  - Role of suppressors of cytokine signaling (Socs) in leukemia inhibitory factor
      (LIF) -dependent embryonic stem cell survival.
AB  - Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the
      presence of leukemia inhibitory factor (LIF). LIF withdrawal results in
      progressive ES cell differentiation. Here we show that during this
      differentiation process, part of the cells undergo apoptosis concomitant with an
      activation of the p38 MAP kinase. To gain insight into events mediated by LIF in
      ES cells, the expression of potential candidate genes was analyzed in the absence
      or presence of this cytokine by using a semiquantitative RT-PCR assay. We focused
      on early response genes and on a new type of cytokine repressors (the Socs
      proteins), some of which exhibit anti-apoptotic properties. We found that
      expression of c-Fos, c-Jun, and JunB was induced upon LIF treatment whereas that
      of JunD, the tyrosine phosphatase ESP, and the components of the LIF receptor
      remained unaffected. Expression of Socs-3, but not Socs-1 or Socs-2, was
      stimulated in the presence of LIF. Finally, uncontrolled overexpression of Socs-1
      and Socs-3 led to repression of LIF-dependent transcription and severely reduced
      cell viability, suggesting that the disturbance of a well balanced Socs protein
      content has adverse effects on cell survival.

PMID- 10928993
TI  - Regional methylation of the 5' end CpG island of BRCA1 is associated with reduced
      gene expression in human somatic cells.
AB  - In mammalians, demethylation of specific promoter regions often correlates with
      gene activation; inversely, dense methylation of CpG islands leads to gene
      silencing, probably mediated by methyl-CpG binding proteins. In cell lines and
      cancers, inhibition of tissue-specific genes and tumor suppressor genes
      expression seems to be related to such hypermethylation. The 5' end of the breast
      cancer predisposition gene BRCA1 is embedded in a large CpG island of
      approximately 2.7 kb in length. In human sporadic breast cancers, the down
      regulation of BRCA1 does not seem to be related to BRCA1 gene alterations.
      Southern blot analysis and the bisulfite sequencing method indicate that the
      BRCA1 CpG island is regionally methylated in all human tissues analyzed and
      unmethylated in the gametes, suggesting a role for DNA methylation in the control
      of gene expression. We have therefore investigated the potential role of methyl
      CpG binding proteins in the regulation of BRCA1 gene expression. In vitro,
      partial methylation of constructs containing this region strongly inhibits gene
      expression in the presence of MeCP2 protein. Moreover, in the five human cell
      lines analyzed, chemically induced hypomethylation is associated with BRCA1 gene
      activation. These data suggest that methyl-CpG binding proteins might be
      associated with the control of BRCA1 gene expression and that methyl-DNA binding
      proteins may participate in the regulation of gene expression in mammalian cells.

PMID- 10928994
TI  - Molecular misreading in non-neuronal cells.
AB  - +1 Frame-shifted proteins such as amyloid precursor protein(+1) and ubiquitin
      B(+1) have been identified in the neuropathological hallmarks of Alzheimer's
      disease. These frameshifts are caused by dinucleotide deletions in GAGAG motifs
      of messenger RNA encoded by genes that have maintained the unchanged wild-type
      DNA sequence. This process is termed 'molecular misreading'. A key question is
      whether this process is confined to neurons or whether it could also occur in non
      neuronal cells. A transgenic mouse line (MV-B) carrying multiple copies of a rat
      vasopressin minigene as a reporter driven by the MMTV-LTR promotor was used to
      screen non-neuronal tissues for molecular misreading by means of detection of the
      rat vasopressin(+1) protein and mutated mRNA. Molecular misreading was
      demonstrated to occur in several organs (e.g., epididymis and the parotid gland)
      where transgenic vasopressin expression is abundant, but its penetrance is
      variable both between and within tissues. This implies that non-neural tissues
      too, could be affected by cellular derangements caused by molecular misreading.

PMID- 10928995
TI  - Dengue virus nonstructural protein 1 is expressed in a glycosyl
      phosphatidylinositol-linked form that is capable of signal transduction.
AB  - Dengue virus nonstructural protein 1 (NS1) is expressed on the surface of
      infected cells and is a target of human antibody responses to dengue virus
      infection. We show here that dengue virus uses the cellular glycosyl
      phosphatidylinositol (GPI) linkage pathway to express a GPI-anchored form of NS1
      and that GPI anchoring imparts a capacity for signal transduction in response to
      binding of NS1-specific antibody. This study is the first to identify GPI linkage
      of a virus-encoded protein. The GPI anchor addition signal for NS1 was
      identified, by transfection of HeLa cells with dengue cDNA constructs, as a
      downstream hydrophobic domain in NS2A. GPI linkage of NS1 in both transfected and
      infected cells was demonstrated by cleavage of NS1 from the surface by PI
      specific phospholipase C and by metabolic incorporation of the GPI-specific
      components ethanolamine and inositol. In common with other GPI-anchored proteins,
      addition of specific antibody resulted in signal transduction, as evidenced by
      tyrosine phosphorylation of cellular proteins. Antibody-induced signal
      transduction by GPI-linked NS1 suggests a mechanism of cellular activation that
      may contribute to the pathogenesis of human dengue disease. Signal transduction
      by a GPI-anchored viral antigen interacting with a specific antibody that it
      induces is a new concept in the pathogenesis of viral disease.

PMID- 10928996
TI  - Characterization of novel UCP5/BMCP1 isoforms and differential regulation of UCP4
      and UCP5 expression through dietary or temperature manipulation.
AB  - Mitochondrial uncoupling proteins have been implicated in the maintenance of
      metabolic rate and adaptational thermoregulation. We recently reported the
      identification of a brain-specific mitochondrial uncoupling protein homologue,
      UCP4. Here we characterized another newly described member of the uncoupling
      protein family, termed UCP5 (also called BMCP1). UCP5 transcripts are present in
      multiple human and mouse tissues, with an especially high abundance in the brain
      and testis. Expression of UCP5 in mammalian cells reduces the mitochondrial
      membrane potential. Multiple isoforms of UCP5 were identified and exhibited
      tissue-specific distribution and different potency in reduction of membrane
      potential. Furthermore, the mRNA abundance of both UCP4 and UCP5 is modulated by
      nutritional status or temperature in a tissue-specific manner in mice. Brain UCP4
      and UCP5 mRNA transcripts rose by 1.5- and 1.7-fold, respectively, and liver UCP5
      expression increased by 1.8-fold in response to acute cold exposure. A high-fat
      diet increased UCP5 mRNA in liver by 1.6-fold selectively in the obesity
      resistant A/J but not in the obesity-prone C57BL/6J mouse strain. Liver UCP5
      expression decreased significantly with a 24 h fast and was restored to the
      normal level after refeeding. In contrast, brain transcripts for both genes were
      not significantly altered by fasting or high-fat diet. These findings are
      consistent with the notion that UCP4 and UCP5 may be involved in tissue-specific
      thermoregulation and metabolic changes associated with nutritional status.

PMID- 10928997
TI  - A role for tyrosine phosphorylation in the regulation and sensitization of
      adenylate cyclase by melatonin.
AB  - Mimicking short photoperiod melatonin signals (16 h exposure) on primary cell
      cultures of melatonin target cells of the ovine pars tuberalis (PT) results in an
      enhanced cAMP response to forskolin stimulation relative to untreated cells, a
      phenomenon termed sensitization. The sensitized response of PT cells may be an
      important aspect of the interpretation of the melatonin signal to initiate
      appropriate seasonal physiological responses. The aim of this study is to add to
      our understanding of the molecular mechanisms involved in the sensitization of PT
      cells by melatonin. We demonstrate that sensitization of PT cells by melatonin is
      mediated via a G(i)-coupled melatonin receptor. The sensitized cAMP response is
      not only obtained with the pharmacological tool forskolin, but also with cholera
      toxin, an activator of G(salpha). Changes in the level of G(salpha) or G(ialpha)
      G-protein subunits are ruled out as part of the sensitization mechanism. However,
      changes in tyrosine phosphorylation may be involved as tyrosine kinase inhibitors
      sensitize ovine PT cells and tyrosine phosphatase inhibitors significantly blunt
      adenylate cyclase activity, including the sensitized response to melatonin. The
      adenylate cyclase isoforms mediating the sensitized response may be broad as 7 of
      the 9 isoforms of adenylate cyclase are expressed in the PT.

PMID- 10928999
TI  - Isolation of translationally controlled mRNAs by differential screening.
AB  - Translationalregulation plays an important role in the control of gene
      expression. Changes in translation initiation rates are the most common
      translation-regulating mechanisms, resulting in alterations in mRNA loading of
      ribosomes. This differential mobilization of mRNAs onto polyribosomes was used in
      differential screening to directly identify cDNAs whose transcripts are
      translationally controlled during antigenic stimulation of primary human T
      lymphocytes. Ribosome-free and polysome-bound mRNAs were prepared from quiescent
      and activated T cells and used as templates to synthesize four cDNA pools. These
      in turn were used as probes to hybridize four identical replicas of a T cell
      library or, alternatively, four cDNA arrays. Translational activation was
      indicated by redistribution of the hybridization signals from the ribosome-free
      fraction in resting T cells to the polysome-associated fraction in activated T
      cells. Translational repression corresponded to the opposite hybridization
      pattern. Fifty-two cDNAs were identified as translationally controlled by
      screening 472 genes in a cDNA array; 12 additional ones were obtained by
      screening a cDNA library. Several of the transcripts corresponded to mRNAs
      previously reported to be translationally controlled, thus validating the method.
      For the majority, however, such regulation had not yet been described.
      Translational control was verified for representative examples by demonstrating
      the redistribution of the corresponding mRNAs on polysome gradients in response
      to T cell activation. Our strategy therefore provides an efficient tool to
      directly isolate or identify translationally controlled mRNAs in a variety of
      physiological situations. Moreover, differential screening using arrays enables
      simultaneous analysis of both transcriptional and translational regulation,
      further enhancing the power of gene expression analysis.

PMID- 10928998
TI  - HGF/scatter factor selectively promotes cell invasion by increasing integrin
      avidity.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) controls a genetic program known
      as 'invasive growth', which involves as critical steps cell adhesion, migration,
      and trespassing of basement membranes. We show here that in MDA-MB-231 carcinoma
      cells, these steps are elicited by HGF/SF but not by epidermal growth factor
      (EGF). Neither factor substantially alters the production or activity of
      extracellular matrix proteases. HGF/SF, but not EGF, selectively promotes cell
      adhesion on laminins 1 and 5, fibronectin, and vitronectin through a PI3-K
      dependent mechanism. Increased adhesion is followed by enhanced invasiveness
      through isolated matrix proteins as well as through reconstituted basement
      membranes. Inhibition assays using function-blocking antibodies show that this
      phenomenon is mediated by multiple integrins including beta1, beta3, beta4, and
      beta5. HGF/SF triggers clustering of all these integrins at actin-rich adhesive
      sites and lamellipodia but does not quantitatively modify their membrane
      expression. These data suggest that HGF/SF promotes cell adhesion and
      invasiveness by increasing the avidity of integrins for their specific ligands.

PMID- 10929001
TI  - Function and structure of Drosophila glycans.
AB  - Through the application of classic organismal genetic strategies, such as
      mutagenesis and interaction screens, Drosophila melanogaster provides
      opportunities to understand glycan function. For instance, screens for Drosophila
      genes that establish dorsal-ventral polarity in the embryo or that influence
      cellular differentiation through signal modulation have identified putative
      glycan modifying enzymes. Other genetic and molecular approaches have
      demonstrated the existence of phylogenetically conserved and novel
      oligosaccharide processing activities and carbohydrate binding proteins. While
      the structural characterization of Drosophila oligosaccharide diversity has
      lagged behind the elucidation of glycan function, landmarks are becoming apparent
      in the carbohydrate terrain. For instance, O-linked GlcNAc and mucins, spatially
      and temporally regulated N-linked oligosaccharide expression, glycosphingolipids,
      heparan sulfate, chondroitin sulfate and polysialic acid have all been described.
      A major challenge for Drosophila glycobiology is to expand the oligosaccharide
      structural database while endeavoring to link glycan characterization to
      functional analysis. The completion of the Drosophila genome sequencing project
      will yield a broad portfolio of glycosyltransferases, glycan modifying enzymes
      and lectins requiring characterization. To this end, the great range of genetic
      tools that allow the controlled spatial and temporal expression of transgenes in
      Drosophila will permit unprecedented manipulation of glycosylation in a whole
      organism.

PMID- 10929000
TI  - Protein kinase calpha targeting is regulated by temporal and spatial changes in
      intracellular free calcium concentration [Ca(2+)](i).
AB  - Protein kinase C (PKC) isoforms exert specific intracellular functions, but the
      different isoforms display little substrate specificity in vitro. Selective PKC
      isoform targeting may be a mechanism to achieve specificity. We used a green
      fluorescent fusion protein (GFP) to test the hypothesis that local changes in
      [Ca(2+)](i) regulate translocation of PKCalpha and that different modes of Ca(2+)
      and Ca(2+) release play a role in PKCalpha targeting. We constructed deletion
      mutants of PKCalpha to analyze the Ca(2+)-sensitive domains and their role in
      targeting. Confocal microscopy was used and [Ca(2+)](i) was measured by fluo-3.
      The fusion protein PKCalpha-GFP was expressed in vascular smooth muscle cells and
      showed a cytosolic distribution similar to the wild-type PKCalpha protein. The
      Ca(2+) ionophore ionomycin induced a speckled cytosolic PKCalpha-GFP
      distribution, followed by membrane translocation, while depolarization by KCl
      induced primarily membrane translocation. Selective voltage-operated Ca(2+)
      channel opening led to a localized accumulation of PKCalpha-GFP near the plasma
      membrane. Opening Ca(2+) stores with InsP(3), thapsigargin, or ryanodine induced
      a specific PKCalpha-GFP targeting to distinct intracellular areas. The G-protein
      coupled receptor agonist thrombin induced a rapid translocation of the fusion
      protein to focal domains. The tyrosine kinase receptor agonist PDGF induced
      Ca(2+) influx and led to a linear PKCalpha-GFP membrane association. PKCalpha-GFP
      deletion mutants demonstrated that the C2 domain, but not the catalytic subunit,
      is necessary for Ca(2+)-induced PKCalpha targeting. Targeting was also abolished
      when the ATP binding site was deleted. We conclude that PKCalpha can rapidly be
      translocated to distinct intracellular or membrane domains by local increases in
      [Ca(2+)](i). The targeting mechanism is dependent on the C2 and ATP binding site
      of the enzyme. Localized [Ca(2+)](i) changes determine the spatial and temporal
      targeting of PKCalpha.

PMID- 10929002
TI  - The human gastric colonizer Helicobacter pylori: a challenge for host-parasite
      glycobiology.
AB  - The Gram-negative bacterium Helicobacter pylori was first described in 1983 and
      currently represents one of the most active single research topics in
      biomedicine. It is specific for the human stomach and chronically colonizes a
      majority of the global population, which results in a symptom-free local
      inflammation. In 10-20% of carriers, gastroduodenal disease develops, including
      gastric or duodenal ulcer, and atrophic gastritis, which is a precondition to
      gastric cancer. A probable long coevolution of microbe and homo sapiens in a
      restricted niche has apparently generated a complex and sophisticated interplay.
      Access to complete bacterial genome sequences assists in a comparative functional
      characterization. A dynamic glycosylation of both microbe and host cells is of
      growing interest to analyze. Several glycoforms of bacterial surface
      lipopolysaccharides show advanced molecular mimicry of host epitopes and a
      distinct phase variation. An unusually large family of 32 outer membrane proteins
      probably reflects the complex interrelationship with the host. The unique
      diversity found for carbohydrate-binding specificities may be mediated by these
      surface proteins, of which the Lewis b-binding adhesin is the only known example
      so far, and these binding activities are subject to phase variation. The host
      mucosa glycosylation may also vary with different conditions, allowing a
      modulated crosstalk between microbe and host. The bacterium actively stimulates
      the host inflammatory response, apparently for nutritional purposes, and there is
      no evidence for a spontaneous elimination of the microbe. Colonization appears to
      be preventive for upper stomach and esophageal diseases. Current antibiotic
      treatment eradicates the microbe and cures ulcer disease. Alternative approaches
      must, however, be developed for a potential global prevention of disease.

PMID- 10929003
TI  - A sulfated polysaccharide from the sarcoplasmic reticulum of sea cucumber smooth
      muscle is an endogenous inhibitor of the Ca(2+)-ATPase.
AB  - Vesicles derived from the endoplasmic reticulum of sea cucumber smooth muscle
      retain a membrane bound Ca(2+)-ATPase that is able to transport Ca(2+) into the
      vesicles at the expense of ATP hydrolysis. In contrast with vesicles obtained
      from rabbit muscles, the activity of the Ca(2+)-dependent ATPase from sea
      cucumber is dependent on monovalent cations (K(+)>Na(+)>Li(+)). With the addition
      of highly sulfated polysaccharide to vesicle preparations from rabbit muscle,
      Ca(2+) uptake decreases sharply and becomes highly sensitive to monovalent
      cations, as observed with vesicles from sea cucumber muscle. These results led us
      to investigate the possible occurrence of a highly sulfated polysaccharide on
      vesicles from the endoplasmic reticulum of sea cucumber smooth muscle, acting as
      an "endogenous" Ca(2+)-ATPase inhibitor. In fact, vesicles derived from the
      invertebrate, but not from rabbit muscle, contain a highly sulfated
      polysaccharide. This compound inhibits Ca(2+) uptake in vesicles obtained from
      rabbit muscle and the inhibition is antagonized by monovalent cation. In
      addition, sea cucumber muscles contain high concentrations of another
      polysaccharide, which surrounds the muscle fibers, and was characterized as a
      fucosylated chondroitin sulfate. Possibly the occurrence of sulfated
      polysaccharides in the sea cucumber muscles is related with unique properties of
      the invertebrate body wall, which can rapidly and reversibly alter its mechanical
      properties, with change in length by more than 200%.

PMID- 10929004
TI  - Novel immunogenicity of Thomsen-Friedenreich disaccharide obtained by a molecular
      rotation on its carrier linkage.
AB  - The alpha-anomeric Galbeta1-3GalNAc, called Thomsen-Friedenreich disaccharide
      (TFD), is overexpressed in epithelial cancer cells by aberrant O-glycosylation.
      TFD is also the main ligand of Agaricus bisporus lectin (ABL), a reversible
      noncytotoxic inhibitor of proliferation of epithelial cell lines. In order to
      obtain anti-TFD antibody response with a fine carbohydrate-binding specificity
      similar to that of ABL, we designed an immunogen of TFD with a molecular rotation
      on its carrier linkage that exposes more GalNAc than Gal, since ABL recognizes
      GalNAc more than Gal in TFD. The synthesis was accomplished by C-6 oxidation of
      Gal from TFD or its alpha-benzyl derivative (BzlalphaTFD), followed by reductive
      amination between the C-6 aldehyde yielded and the available amine of protein.
      Mice immunized with TFD-KLH (keyhole limpet hemocyanin) or BzlalphaTFD-KLH
      produced antibodies which were then analyzed by ELISA against several target
      antigens. Both immunogens raised anti-KLH antibody titers; however, TFD-KLH did
      not raise anti-TFD antibodies showing low TFD immunogenicity. In contrast,
      BzlalphaTFD-KLH gave much higher anti-TFD antibody response, indicating that
      benzyl residue helps improve anti-carbohydrate immune response. When IgG and IgM
      anti-TFD antibodies were analyzed by competitive ELISA using TFD-related
      carbohydrates as inhibitors, a high specificity to TFD as well as an enhanced
      binding to GalNAc over Gal were observed. The axial C-4 hydroxyl group of GalNAc
      interacted with IgG anti-TFD antibody, as evidenced by the lack of inhibitory
      activity of GlcNAc in contrast to GalNAc. These findings indicate that the anti
      TFD antibodies have fine carbohydrate-binding specificity more similar to ABL
      than to other TFD-binding proteins that stimulate proliferation of epithelial
      cell lines.

PMID- 10929005
TI  - FUT4 and FUT9 genes are expressed early in human embryogenesis.
AB  - The Le(x) oligosaccharide is expressed in organ buds progressing in mesenchyma,
      during human embryogenesis. Myeloid-like alpha3-fucosyltransferases are good
      candidates to synthesize this oligosaccharide. We investigated by Northern
      analysis all the alpha3-fucosyltransferase gene transcripts and only FUT4 and
      FUT9 were detected. The enzymes encoded by the FUT4 and FUT9 genes are the first
      alpha3-fucosyltransferases strongly expressed during the first two months of
      embryogenesis. The Northern profile of expression of the embryo FUT4 transcripts
      is similar in size and sequence to the known FUT4 transcripts of 6 kb, 3 kb, and
      2.3 kb, but a new FUT9 transcript of 2501 bp, different from the known mouse
      (2170 bp) and human (3019 bp) transcripts was cloned. FUT3, FUT5, FUT6, and FUT7
      were not detected by Northern blot. The FUT3 and FUT6 transcripts start to appear
      at this stage, but are only detected by reverse transcriptase-PCR analysis. The
      expression of FUT5 is weaker than FUT3 and FUT6 and the RT-PCR signal is faint
      and irregular. FUT7 is not detected at all. Using mRNA from 40- to 65-day-old
      embryos, we have prepared different hexamer and oligo-dT cDNA libraries and
      cloned, by rapid amplification cDNA ends-PCR, FUT4 and FUT9 alpha3
      fucosyltransferase transcripts. The tissue expression of the embryonic FUT9
      transcript is closer to that observed for the mouse (brain), than to the known
      human (stomach) transcripts. The acceptor specificity and the kinetics of the
      alpha3-fucosyltransferase encoded by this FUT9 transcript are similar to the FUT4
      enzyme, except for the utilization of the lac-di-NAc acceptor which is not
      efficiently transformed by the FUT9 enzyme. Like FUT4, this embryonic FUT9 is N
      ethylmaleimide and heat resistant and the corresponding gene was confirmed to be
      localized in the chromosome band 6q16. Finally, this FUT9 transcript has a single
      expressed exon as has been observed for most of the other vertebrate alpha2- and
      alpha3-fucosyltransferases.

PMID- 10929006
TI  - Purification and some properties of UDP-xylosyltransferase of rat ear cartilage.
AB  - UDP-xylosyltransferase (UDP-D-xylose:proteoglycan core protein beta-D
      xylosyltransferase EC 2.4.2.26) initiates the formation of chondroitin sulfate in
      the course of proteoglycan biosynthesis. The enzyme catalyzes the transfer of D
      xylose from UDP-D-xylose to specific serine residues in the core protein. A
      procedure for purification of xylosyltransferase from rat ear cartilage was
      developed which includes ammonium sulfate fractionation, chromatography on
      heparin-agarose, on Sephacryl S300 and finally a substrate affinity
      chromatography applying the dodeca peptide Q-E-E-E-G-S-G-G-G-Q-G-G. The specific
      activity of the purified enzyme was about 420 mU per mg protein. The purification
      factor was about 26.000 with 27% yield. In SDS-polyacrylamide gel
      electrophoresis, the highly purified enzyme is homogeneous and yields only a
      single distinct band of 78 kDa. An apparent molecular mass of 71 kDa was
      determined for the native enzyme. These data suggest a monomeric structure for
      the enzyme. Xylosyltransferase activity was found to depend essentially on the
      presence of divalent metal ions. The K(m) value for UDP-D-xylose was determined
      to 6.5 micromol/l and for the dodeca peptide Q-E-E-E-G-S-G-G-G-Q-G-G as xylose
      acceptor to 8 micromol/l.

PMID- 10929007
TI  - Cloning and expression of beta1,4-galactosyltransferase gene from Helicobacter
      pylori.
AB  - Helicobacter pylori, which is a human pathogen associated with gastric and
      duodenal ulcer, has been shown to express human oncofetal antigens Lewis X and
      Lewis Y. Although the mammalian glycosyltransferases that synthesize these
      structures are well characterized, little is known about the corresponding
      bacterial enzymes. We report that a novel beta1,4-galactosyltransferase gene
      (HpgalT) involved in the biosynthesis of lipopolysaccharides in H. pylori has
      been cloned and expressed in Escherichia coli. The deduced amino acid sequence of
      the protein (HpGal-T) encoded by HpgalT consists of 274 residues with the
      calculated molecular mass of 31,731 Da, which does not show significant
      similarity to those of beta1,4-galactosyltransferases from mammalian sources and
      Neisseria It was confirmed that HpGal-T catalyzed the introduction of galactose
      from UDP-Gal in a beta1,4 linkage to accepting N-acetylglucosamine (GlcNAc)
      residues by means of high-performance anion-exchange chromatography with pulsed
      amperometric detection (HPAEC-PAD). When the E.coli cells which overexpressed
      HpgalT was coupled with the UDP-Gal production system, which consisted of
      recombinant E.coli cells overexpressing its UDP-Gal biosynthetic genes and
      Corynebacterium ammoniagenes, N-acetyllactosamine, a core structure of
      lipopolysaccharide of H.pylori, was efficiently produced from orotic acid,
      galactose, and GlcNAc.

PMID- 10929008
TI  - The heterodimeric structure of glucosidase II is required for its activity,
      solubility, and localization in vivo.
AB  - Glucosidase II is an ER heterodimeric enzyme that cleaves sequentially the two
      innermost alpha-1,3-linked glucose residues from N-linked oligosaccharides on
      nascent glycoproteins. This processing allows the binding and release of
      monoglucosylated (Glc(1)Man(9)GlcNAc(2)) glycoproteins with calnexin and
      calreticulin, the lectin-like chaperones of the endoplasmic reticulum. We have
      isolated two cDNA isoforms of the human alpha subunit (alpha1 and alpha2)
      differing by a 66 bp stretch, and a cDNA for the corresponding beta subunit. The
      alpha1 and alpha2 forms have distinct mobilities on SDS-PAGE and are expressed in
      most of the cell lines we have tested, but were absent from the glucosidase II
      deficient cell line PHA(R) 2.7. Using COS7 cells, the coexpression of the beta
      subunit with the catalytic alpha subunit was found to be essential for enzymatic
      activity, solubilization, and/or stability, and ER retention of the alpha/beta
      complex. Transfected cell extracts expressing either alpha1 or alpha2 forms with
      the beta subunit showed similar activities, while mutating( )the nucleophile
      (D542N) predicted from the glycoside hydrolase Family 31 active site consensus
      sequence abolished enzymatic activity. In order to compare the kinetic parameters
      of both alpha1/beta and alpha2/beta forms of human glucosidase II the protein was
      expressed with the baculovirus expression system. Expression of the human alpha
      or beta subunit alone led to the formation of active human/insect heteroenzymes,
      demonstrating functional complementation by the endogenous insect glucosidase II
      subunits. The activity of both forms of recombinant human glucosidase II was
      examined with a p-nitrophenyl alpha-D-glucopyranoside substrate, and a two
      binding site kinetic model for this substrate was shown. The K(M1-2) values and
      apparent K(i1-2 )for deoxynojirimycin and castanospermine were determined and
      found to be identical for both isoforms suggesting they have similar catalysis
      and inhibition characteristics. The substrate specificities of both isoforms
      using the physiological oligosaccharides were assessed and found to be similar.

PMID- 10929009
TI  - Mannose supplementation corrects GDP-mannose deficiency in cultured fibroblasts
      from some patients with Congenital Disorders of Glycosylation (CDG).
AB  - Congenital Disorders of Glycosylation (CDG) are human deficiencies in
      glycoprotein biosynthesis. Previous studies showed that 1 mM mannose corrects
      defective protein N-glycosylation in cultured fibroblasts from some CDG patients.
      We hypothesized that these CDG cells have limited GDP-mannose (GDP-Man) and that
      exogenous mannose increases the GDP-Man levels. Using a well established method
      to measure GDP-Man, we found that normal fibroblasts had an average of 23.5 pmol
      GDP-Man/10(6) cells, whereas phosphomannomutase (PMM)-deficient fibroblasts had
      only 2.3-2.7 pmol/10(6) cells. Adding 1 mM mannose to the culture medium
      increased the GDP-Man level in PMM-deficient cells to approximately 15.5
      pmol/10(6) cells, but had no significant effect on GDP-Man levels in normal
      fibroblasts. Similarly, mannose supplementation increased GDP-Man from 4.6
      pmol/10(6) cells to 24.6 pmol/10(6) cells in phosphomannose isomerase (PMI)
      deficient fibroblasts. Based on the specific activity of the GDP-[(3)H]Man pool
      present in [2-(3)H]mannose labeled cells, mannose supplementation also partially
      corrected the impaired synthesis of mannosylphosphoryldolichol (Man-P-Dol) and
      Glc(0)(-)(3)Man(9)GlcNAc(2)-P-P-Dol. These results confirm directly that
      deficiencies in PMM and PMI result in lowered cellular GDP-Man levels that are
      corrected by the addition of mannose. In contrast to these results, GDP-Man
      levels in fibroblasts from a CDG-Ie patient, who is deficient in Man-P-Dol
      synthase, were normal and unaffected by mannose supplementation even though
      mannose addition was found to correct abnormal lipid intermediate synthesis in
      another study (Kim et al. [2000] J. Clin. Invest., 105, 191-198). The mechanism
      by which mannose supplementation corrects abnormal protein N-glycosylation in Man
      P-Dol synthase deficient cells is unknown, but this observation suggests that the
      regulation of Man-P-Dol synthesis and utilization may be more complex than is
      currently understood.

PMID- 10929015
TI  - Capnocytophaga canimorsus, a potential emerging microorganism in splenectomized
      patients.

PMID- 10929010
TI  - N-glycan patterns of human transferrin produced in Trichoplusia ni insect cells:
      effects of mammalian galactosyltransferase.
AB  - The N-glycans of human serum transferrin produced in Trichopulsia ni cells were
      analyzed to examine N-linked oligosaccharide processing in insect cells.
      Metabolic radiolabeling of the intra- and extracellular protein fractions
      revealed the presence of multiple transferrin glycoforms with molecular weights
      lower than that observed for native human transferrin. Consequently, the N-glycan
      structures of transferrin in the culture medium were determined using three
      dimensional high performance liquid chromatography. The attached oligosaccharides
      included high mannose, paucimannosidic, and hybrid structures with over 50% of
      these structures containing one fucose, alpha(1,6)-, or two fucoses, alpha(1,6)-
      and alpha(1,3)-, linked to the Asn-linked N-acetylglucosamine. Neither sialic
      acid nor galactose was detected on any of the N-glycans. However, when
      transferrin was coexpressed with beta(1,4)-galactosyltransferase three additional
      galactose-containing hybrid oligosaccharides were obtained. The galactose
      attachments were exclusive to the alpha(1, 3)-mannose branch and the structures
      varied by the presence of zero, one, or two attached fucose residues.
      Furthermore, the presence of the galactosyltransferase appeared to reduce the
      number of paucimannosidic structures, which suggests that galactose attachment
      inhibits the ability of hexosaminidase activity to remove the terminal N
      acetylglucosamine. The ability to promote galactosylation and reduce
      paucimannosidic N-glycans suggests that the oligosaccharide processing pathway in
      insect cells may be manipulated to mimic more closely that of mammalian cells.

PMID- 10929016
TI  - Viral inactivation of fresh frozen plasma.

PMID- 10929017
TI  - Optimal blood donation screening annotation.

PMID- 10929018
TI  - Laboratory testing for heritable thrombophilia: impact on clinical management of
      thrombotic disease annotation.

PMID- 10929019
TI  - Guidelines on the investigation and management of the antiphospholipid syndrome.

PMID- 10929020
TI  - Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic
      haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age.
AB  - Transplant-related mortality (TRM) remains a major problem in older patients
      undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have
      therefore explored a less intensive conditioning in 33 patients with a median age
      of 52 years (range 43-60) transplanted from human leucocyte antigen (HLA)
      identical siblings. The underlying disease was chronic myeloid leukaemia (n =
      15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic
      lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The
      regimen consisted of thiotepa (THIO; 10 mg/kg) on day -5 and cyclophosphamide
      (CY; 50 mg/kg) on days -3 and -2 (total dose 100 mg/kg). The source was bone
      marrow (BM) (n = 17) or granulocyte colony-stimulating factor (G-CSF)-mobilized
      peripheral blood (PB) (n = 16), which were infused without manipulation. Graft
      versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a
      short course of methotrexate. Mean time to achieve a neutrophil count of 0.5 x
      109/l was 17 d (range 11-23) and full donor chimaerism was detected in 79% of
      patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients.
      Chronic GVHD was seen in 45% of patients, with a significant difference for PB
      (69%) compared with BM transplants (23%) (P = 0.009). For BM grafts, the
      actuarial 2-year TRM was 6%, the relapse 56% and survival 87%; for PB grafts,
      these figures were, respectively, 27%, 33% and 68%. Twenty-five patients are
      alive at a median follow-up of 762 d (range 216-1615) and 20 patients (60%)
      remain free of disease. Thirteen patients (39%) received donor lymphocyte
      infusion (DLI) either for persisting or relapsing disease and six patients had
      complete remission. IN CONCLUSION: (i) patients up to the age of 60 years can be
      allografted with reduced intensity conditioning; (ii) the procedure was
      associated with a low transplant-related mortality, particularly for bone marrow
      grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required
      after transplant in half the patients for persisting disease or relapse.

PMID- 10929021
TI  - Second chronic phase before transplantation is crucial for improving survival of
      blastic phase chronic myeloid leukaemia.
AB  - Because successful outcome after transplantation seems to depend in acute myeloid
      leukaemia (AML) and in chronic phase chronic myeloid leukaemia (CML) on disease
      status at the time of transplantation, we investigated whether FLAN (fludarabine,
      cytosine arabinoside, mitoxantrone) induction before allogeneic stem cell
      transplantation (allo-SCT) may be useful in blastic phase (BP)-CML. Twenty
      patients with BP-CML were studied: 10 patients received FLAN induction
      chemotherapy before proceeding to early allo-SCT, whereas 10 patients were
      submitted to bone marrow transplantation (BMT) without remission induction. Eight
      out of 10 (80%) patients achieved second chronic phase after one course of
      therapy with FLAN and seven patients (six in second chronic phase and one with
      partial response) were then submitted to allo-SCT. Of the six patients
      transplanted in the second chronic phase, all achieved molecular remission, four
      are still in second chronic phase, with intervals ranging from 10 to 54 months,
      whereas one patient died from infection having relapsed 14 months after SCT and
      one died of transplant-related complications in the second chronic phase. Mean
      durations of second chronic phase and survival after allo-SCT were both
      significantly longer than in the group of 10 BP-CML patients submitted to allo
      SCT without FLAN remission induction treatment [22.4 (range 1-61) vs. 3.5 months
      (range 1-10) with FLAN and 22.7 (range 2-61) vs. 6.4 (range 1-16) months without
      FLAN]. We conclude that FLAN induction therapy followed by early allo-SCT appears
      to be effective in the treatment of BP-CML and could provide a curative
      possibility for BP-CML patients.

PMID- 10929022
TI  - In vivo depletion of B cells using a combination of high-dose cytosine
      arabinoside/mitoxantrone and rituximab for autografting in patients with non
      Hodgkin's lymphoma.
AB  - We performed a pilot study including rituximab (Mabthera; IDEC-C2B8, Hoffmann-La
      Roche) with a sequential high-dose therapy protocol in 15 patients with
      follicular and three patients with mantle cell lymphoma and studied the potential
      of the chemoimmunotherapy to induce depletion of malignant B cells in vivo. Our
      treatment protocol included induction with three cycles of CHOP
      (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy,
      followed by peripheral blood stem cell (PBSC) mobilization using high-dose
      cytosine arabinoside (2 g/m2 every 12 h, days 1 and 2) and mitoxantrone (10
      mg/m2, days 2 and 3) (HAM), preceeded by rituximab (375 mg/m2). The proportion of
      CD19+ B cells in blood and bone marrow decreased from 1.2 +/- 0.4% to 0.13 +/- 0.
      1% (P = 0.01) and from 2.7 +/- 0.8% to 0.8 +/- 0.5% (P = 0.03) respectively. The
      number of t(14;18)-positive cells in blood and bone marrow progressively
      decreased with treatment, as assessed by the quantitative real-time PCR assay in
      four patients. Conversion to PCR-negativity was achieved in the peripheral blood
      (PB) of seven informative patients. Leucaphereses were performed during the
      granulocyte colony-stimulating factor (G-CSF)-supported leucocyte recovery phase.
      In 17 of 18 patients, a median of 15.1 x 106 CD34+ cells/kg body weight (BW)
      could be harvested by a single procedure for enrichment by an immunomagnetic
      method. Leucapheresis products contained 51.3 +/- 28.8 x 104 CD19+ B cells/kg BW
      (mean) and were t(14;18) PCR negative in all seven informative patients. These
      data compare favourably with results obtained in patients treated with the same
      regimen without rituximab. The high-dose therapy (n = 12 patients), including
      total body irradiation (14.4 Gy) and cyclophosphamide (200 mg/kg BW), was also
      preceeded by rituximab. Recovery of neutrophils to > 0.5 x 109/l and of platelets
      to > 20 x 109/l required a median of 13.5 and 11.5 d (range 11-24 and 9-24 d)
      respectively. In conclusion, the addition of the CD20 antibody to chemotherapy
      ensured tumour depletion in vivo and allowed the collection of PBSCs devoid of
      tumour cells and with conserved engraftment capability.

PMID- 10929023
TI  - Autologous stem cell transplantation for anaplastic large-cell lymphomas: results
      of a prospective trial.
AB  - Autologous stem cell transplantation (ASCT) in the front line treatment of non
      Hodgkin's lymphoma (NHL) remains controversial. Anaplastic large-cell lymphoma
      (ALCL) is known to have its own clinical and biological features. The outcome of
      ALCL patients treated with high-dose chemotherapy and ASCT as part of their first
      line therapy was analysed in 202 intermediate or high-grade NHL patients in a
      prospective randomized trial. First-line chemotherapy comprised two alternating
      anthracycline-containing regimens. Responding patients were autografted after a
      BEAM (BCNU, cytarabine, etoposide and melphalan) regimen. Patients with bulky or
      residual masses were irradiated. Fifteen patients with ALCL were identified by
      morphological and immunological features (CD30 was expressed in 14 out of 15
      patients, three patients expressed B-cell markers, five patients expressed T-cell
      markers and seven patients did not express cell markers). Anaplastic lymphoma
      kinase (ALK) expression was confirmed in seven cases. The median age was 39 years
      with a predominant male sex ratio (2.75). Thirteen patients were stage >/= III
      and six presented with two or more adverse prognostic factors. According to the
      international age-adjusted prognostic index, the expected complete remission
      (CR), event-free survival (EFS) and overall survival (OS) rates were 69%, 71% and
      69%. Two deaths were observed (one due to interstitial pneumonitis, one due to
      pulmonary carcinoma). All patients entered CR, no relapse occurred and EFS and
      survival reached 87% with a follow-up of more than 5 years. These results differ
      significantly from those observed in the other 176 lymphoma patients: event-free
      survival was only 53 +/- 5% and OS reached 60 +/- 4% with a median follow-up of
      56 months (P = 0.006). Intensified chemotherapy with autologous stem cell support
      appeared effective in the treatment of ALCL, offering patients the real chance of
      a cure.

PMID- 10929024
TI  - Incidence of mixed chimaerism and clinical outcome in 101 patients after
      myeloablative conditioning regimens and allogeneic stem cell transplantation.
AB  - In the light of reduced intensity conditioning regimens for allogeneic
      transplantation, monitoring of donor cell engraftment acquires new relevance. We
      analysed the clinical significance of haematopoietic chimaerism as a parameter of
      patient outcome and detection of relapse for early intervention by donor
      lymphocyte infusion (DLI) after allogeneic transplantation. Between July 1994 and
      March 1999, 101 adult patients with malignant disease were evaluated. Median
      follow-up was 15 months (range 0.7-56.5) after transplantation. Patients received
      busulphan-containing (n = 82) or total body irradiation (TBI)-containing (n = 19)
      regimens. Fifteen out of 98 (15%) patients with predictive chimaerism analyses
      relapsed, 5 out of 20 (25%) with mixed chimaerism (MC) and 10 out of 78 (13%)
      with complete donor chimaerism (CC) before apparent relapse. Seven patients
      received donor lymphocyte infusions (DLI) as relapse therapy with conversion from
      MC to CC in all three patients with successful DLI. Our data stress the
      importance of chimaerism monitoring after allogeneic transplantation and
      demonstrate the more frequent occurrence of disease relapse in patients showing
      MC, rather than CC, after transplantation. Moreover, the assessment of chimaerism
      has been shown to be a valuable tool in monitoring the efficiency of donor
      lymphocyte infusions for relapse.

PMID- 10929025
TI  - Combination of stem cell factor and granulocyte colony-stimulating factor
      mobilizes the highest number of primitive haemopoietic progenitors as shown by
      pre-colony-forming unit (pre-CFU) assay.
AB  - Fifty-two patients with poor prognosis carcinoma of the breast underwent
      peripheral blood stem cell (PBSC) mobilization using five different regimens. The
      yields of primitive haemopoietic progenitors were quantified by a recently
      described pre-colony-forming unit (pre-CFU) assay using limiting dilution
      analysis (LDA). Results of days 14 and 35 pre-CFU were also correlated with
      conventional CD34+ cell enumeration, CFU-GM (granulocyte-macrophage) and long
      term culture-initiating cell (LTCIC) assays. The yield of pre-CFUs with the
      combination of granulocyte colony-stimulating factor (G-CSF) and stem cell factor
      (SCF) was significantly higher than with G-CSF alone, cyclophosphamide (Cyclo)
      and granulocyte-monocyte colony-stimulating factor (GM-CSF), interleukin (IL)-3
      and GM-CSF, or Cyclo alone. No significant correlation between neutrophil
      engraftment and pre-CFU could be demonstrated. Furthermore, CFU-GM was shown to
      bear a stronger correlation with pre-CFU and LTCIC than CD34+ cell measurement;
      thus, CFU-GM remains a useful biological tool for haemopoietic stem cell assay.
      We conclude that the combination of G-CSF and SCF mobilizes the highest number of
      pre-CFUs as measured by functional pre-CFU assay, which provides an alternative
      measurement of primitive haemopoietic progenitors to the LTCIC assay.

PMID- 10929026
TI  - Restricted usage of T-cell receptor alpha-chain variable region (TCRAV) and T
      cell receptor beta-chain variable region (TCRBV) repertoires after human
      allogeneic haematopoietic transplantation.
AB  - We analysed T-cell receptor alpha-chain variable region (TCRAV) and T-cell
      receptor beta-chain variable region (TCRBV) repertoires in peripheral blood
      mononuclear cells (PBMCs) from 34 recipients of allogeneic bone marrow
      transplantation (allo-BMT), seven of allogeneic peripheral blood stem cell
      transplantation and 19 of autologous peripheral blood stem cell transplantation
      using the quantitative microplate hybridization assay. TCR usage skewed at an
      early period (6-7 weeks) after BMT. The change was more apparent in allogeneic
      recipients than in autologous recipients. In particular, a predominant increase
      was detected in the frequency of VA1-4 (26%, 11 of 41 recipients), VA3-1 (32%)
      and VB24-1 (28%). Interestingly, acidic amino acid residues frequently followed
      the arginine residue in complementarity-determining region 3 of BV24S1. We
      further examined the extent of skew using samples obtained at serial time points
      after transplantation. The normalization of skewed repertoires occurred over a
      long period of time (> 8 years). There was a significant difference in the rate
      of normalization of skewed TCR repertoires between adult and child recipients (P
      < 0.05). The results suggest that these T cells may have expanded in response to
      allogeneic antigens, such as miHA (minor histocompatibility antigen), and that
      altered repertoires are eventually normalized by T-cell regeneration via a thymic
      dependent pathway in children.

PMID- 10929028
TI  - Haematopoietic stem cell transplantation for amegakaryocytic thrombocytopenia.
AB  - Congenital amegakaryocytic thrombocytopenia (CAT), a rare syndrome with failure
      of megakaryopoiesis, cannot be cured by immunoglobulins, steroids or cyclosporin,
      but only by allogeneic bone marrow transplantation (BMT). We report on eight
      patients with CAT, all of whom were dependent at the time of BMT on platelet
      transfusion. Sources of haematopoietic progenitor cells were bone marrow (n = 5),
      peripheral stem cells (n = 2) and cord blood (n = 1). Seven patients engrafted.
      Both patients with matched unrelated donor transplants died, six patients are
      well with stable platelet counts 3-27 months after transplantation. BMT
      represents a curative option for CAT. The benefit of using alternative marrow
      donors should be carefully evaluated.

PMID- 10929027
TI  - A comparative study of once-daily versus twice-daily filgrastim administration
      for the mobilization and collection of CD34+ peripheral blood progenitor cells in
      normal donors.
AB  - Eighty-one first-time normal donors underwent leukapheresis for peripheral blood
      progenitor cell (PBPC) collection after mobilization with filgrastim administered
      either twice-daily (6 microg/kg every 12 h; n = 40) or once-daily (12 microg/kg;
      n = 41) subcutaneously for 3 d. The groups were similar for age, donor blood
      volume and target CD34+ cell dose to be collected (>/= 4 x 106 CD34+ cells/kg
      recipient). There was no statistically significant difference in the apheresis
      yield of CD34+ PBPCs (x 106) per kg recipient weight (5.6 +/- 3.3 vs. 5.6 +/-
      4.3; P = 0.94) and per litre of blood processed (30 +/- 17.2 vs. 30.4 +/- 19.5; P
      = 0.92).

PMID- 10929029
TI  - The in vitro effects of cytokines on expansion and migration of megakaryocyte
      progenitors.
AB  - Increasing the number of megakaryocyte progenitors in stem cell transplants by ex
      vivo expansion culture may be an approach to accelerate platelet recovery in
      patients undergoing high-dose chemotherapy. We evaluated the effect of three
      different cytokine combinations on expansion, with special emphasis on the type
      of colony formation and migration of megakaryocytic cells. The number of
      clonogenic megakaryocyte progenitors (colony-forming units-megakaryocyte; CFU-Mk)
      with high- (> 20 cells/colony) and low-proliferative capacity (5-20 cells/colony)
      and the number of megakaryocytic (CD61+) cells were significantly increased by
      including interleukin 3 (IL-3) or IL-3 + IL-6 + IL-11 + Flt3-ligand to cultures
      containing megakaryocyte growth and development factor (MGDF) plus stem cell
      factor (SCF). No difference in the maturation of megakaryocytes from all three
      cytokine combinations to platelets were observed, as demonstrated by electron
      microscopy. In chemotaxis experiments, the migration towards stromal cell-derived
      factor 1 (SDF-1) was shown to be reduced for CD61+ cells and megakaryocyte
      progenitors cultured in other cytokines besides MGDF + SCF. The reduced migration
      was related to a lower expression of CXCR4, the receptor for SDF-1, on
      megakaryocytes from the proliferating cultures. These in vitro results
      demonstrate that expansion in IL-3 and other cytokines besides MGDF + SCF
      significantly impair the capacity of megakaryocytic cells to migrate.

PMID- 10929030
TI  - Control of pH in human long-term bone marrow cultures with low-glucose medium
      containing zwitterion buffer lengthens the period of haemopoietic activity.
AB  - Primary long-term bone marrow cultures grown in 40 mM HEPES-buffered McCoy's 5A
      medium produced granulocyte-macrophage colony-forming units (CFU-GM) for a median
      of 9 weeks compared with 7 weeks with CO2/bicarbonate-buffered cultures. Reducing
      the medium glucose concentration (from 12.5 to 2.75 mM) extended the culture
      longevity to 17 weeks. The median period of erythroid colony detection increased
      from 6 to 8 weeks. Secondary cultures (5 x 106 cord blood mononuclear cells
      seeded on irradiated stroma) showed statistically similar myeloid and erythroid
      longevity to primary cultures. Improved control of medium pH significantly
      improved the capacity of long-term stromal layers to maintain stem cells in
      vitro.

PMID- 10929031
TI  - t(4;11)(q21;p15) translocation involving NUP98 and RAP1GDS1 genes:
      characterization of a new subset of T acute lymphoblastic leukaemia.
AB  - Two cases of T acute lymphoblastic leukaemia (T-ALL) with an identical
      t(4;11)(q21;p15) translocation were identified within a prospective study on the
      biological and clinical features of adult ALL patients enrolled into the
      therapeutic protocol ALL0496 of the GIMEMA Italian Group. In both cases, the
      molecular characterization showed an involvement of the NUP98 gene on 11p15 which
      rearranges with the RAP1GDS1 gene on 4q21. The morphological and immunological
      features of the leukaemic cells, as well as the clinical behaviour and response
      to induction therapy, were the same in both patients. Based on the available
      data, the t(4;11)(q21;p15) translocation involving the NUP98-RAP1GDS1 fusion gene
      emerges as a new highly specific genetic abnormality that characterizes a subset
      of T-ALL.

PMID- 10929032
TI  - Familial chronic lymphocytic leukaemia: a survey and review of published studies.
AB  - B-cell chronic lymphocytic leukaemia (CLL) is the most common form of leukaemia.
      To gain insight into the role of inherited factors in the disease, we have
      conducted a survey of the family histories of 268 CLL patients and have reviewed
      published familial cases and epidemiological studies. The results of our survey
      and published studies strongly support the hypothesis that a subset of the
      disease can be ascribed to a genetic predisposition. The most likely genetic
      model for inherited predisposition appears to be dominantly acting genes with
      pleiotropic effects because in many families CLL appears to be associated with
      other lymphoproliferative disorders.

PMID- 10929033
TI  - Caspases influence the mode but not the extent of cell death induced by purine
      analogues in chronic lymphocytic leukaemia.
AB  - Caspases are known to be involved in the apoptotic killing of chronic lymphocytic
      leukaemia (CLL) cells by fludarabine. However, it is unclear whether these
      enzymes are required for the induction of such killing, or whether they simply
      determine the mode of cell death. To address this question, we examined the
      effect of the broad-spectrum caspase inhibitor Z-VAD.fmk on six different
      manifestations of nucleoside cytotoxicity. Our results indicate that while
      caspase activity is required for nucleoside-induced poly(ADP-ribose) polymerase
      (PARP) cleavage and DNA fragmentation, other manifestations of cell death
      (mitochondrial depolarization, exposure of phosphatidyl serine, cell membrane
      disruption and cell shrinkage) are caspase independent. By showing that caspases
      influence the mode, but not the extent, of nucleoside cytotoxicity, our results
      exclude defects in these enzymes as a mechanism of nucleoside resistance in CLL.

PMID- 10929034
TI  - Induction therapy consisting of alternating cycles of ranimustine, vincristine,
      melphalan, dexamethasone and interferon alpha (ROAD-IN) and a randomized
      comparison of interferon alpha maintenance in multiple myeloma: a co-operative
      study in Japan.
AB  - This pilot study evaluated the efficacy of a new combination chemotherapy with a
      newly developed nitrosourea derivative ranimustine and evaluated the efficacy of
      interferon alpha (IFN-alpha) maintenance in previously untreated patients with
      multiple myeloma (MM). The induction therapy (ROAD-IN) was a 6-week regimen
      consisting of chemotherapy with ranimustine, vincristine (Oncovin), melphalan
      (Alkeran) and dexamethasone starting on day 1 and IFN-alpha, which was
      administered three times weekly for 3 weeks starting on day 22. This was repeated
      for three cycles. The responders were subsequently randomized into two groups
      that received or did not receive IFN-alpha as maintenance therapy. Of the 164
      patients registered, 161 were evaluated. An objective response to induction
      therapy was seen in 75% of patients; complete remission (CR) in 38 (24%) and
      partial remission (PR) in 82 (51%). The median survival for all patients was 3.6
      years from registration. The survival of responders (CR + PR) was significantly
      better than that of non-responders (median survival 4.3 years vs. 1.4 years; 7
      year survival rate 32% vs. 9%; P < 0.0001). The IFN-alpha maintenance did not
      show any advantage for either response duration or survival. This pilot study
      demonstrated that a comparatively short period of induction therapy with the ROAD
      IN regimen produced a rather high response rate and a similar survival rate to
      those achieved with other longer induction regimens, and that good responders to
      the initial therapy survived significantly longer than non-responders.

PMID- 10929035
TI  - Expression of urokinase plasminogen activator and the urokinase plasminogen
      activator receptor in myeloma cells.
AB  - Binding of urokinase (uPA) to its receptor (uPAR; CD87) focuses proteolytic
      activity on the cell surface and this system is of importance in malignant matrix
      degradation and tumour invasion. By immunocytochemistry and flow cytometry, we
      found that primary myeloma cells and myeloma cell lines expressed uPA and uPAR.
      Soluble uPA was present in cell line supernatants and lysates in low
      concentrations. In cell lines, uPA and uPAR were located both on the cell surface
      and intracellularly, but the expression of both proteins was low. Higher levels
      of uPAR was detected on the cell surface of primary myeloma cells. When primary
      myeloma cells were gated by CD45 expression, stronger expression was found on
      immature CD45+ cells than on mature CD45-/dim cells. Finally, both myeloma cell
      lines and primary cells were able to cleave a uPA-specific substrate showing that
      the uPA system is functionally active. We conclude that myeloma cells are able to
      produce uPA and uPAR. This opens up a possible role of the uPA system in myeloma
      cell invasion and in the proteolytic digestion of bone matrix.

PMID- 10929036
TI  - JAK2 tyrosine kinase inhibitor tyrphostin AG490 downregulates the mitogen
      activated protein kinase (MAPK) and signal transducer and activator of
      transcription (STAT) pathways and induces apoptosis in myeloma cells.
AB  - Cytokines of the interleukin 6 (IL-6) family, which activates the signal
      transducer gp130, are major survival and growth factors for human multiple
      myeloma (MM) cells. The signal transduction of gp130 involves the Janus tyrosine
      kinases (JAK) JAK1, JAK2 and Tyk2 and then the downstream effectors comprising
      the signal transducer and activator of transcription 3 (STAT3) and mitogen
      activated protein kinase (MAPK) pathways. We evaluated the effects of the JAK2
      inhibitor tyrphostin AG490 on MM cells. We found that AG490 suppressed cell
      proliferation and induced apoptosis in IL-6-dependent MM cell lines. JAK2 kinase
      activity, ERK2 and STAT3 phosphorylation were inhibited. These results suggest
      that the chemical blocking of the gp130 signalling pathway at the JAK level could
      be a relevant therapeutic approach to MM.

PMID- 10929037
TI  - TNP-470 and recombinant human interferon-alpha2a inhibit angiogenesis
      synergistically.
AB  - The hypothesis that the combination of two known antiangiogenic agents TNP-470
      and interferon (IFN)-alpha exerts synergistic effects has been investigated in
      vitro and in vivo. In vitro, TNP-470 and recombinant human IFN-alpha2a (rhIFN
      alpha2a) resulted in a dose-dependent inhibition of proliferation of human
      umbilical vein endothelial cells (HUVECs) and EA.hy926 endothelial cells.
      Compared with the two agents used singly at their lowest or ineffective doses,
      combined treatment with the same doses inhibited more intensely in the absence of
      cytotoxicity and displayed similar behaviour on cell chemotaxis and capillary
      morphogenesis on Matrigel. However, the secretion of matrix metalloproteinase 2
      (MMP-2) and MMP-9 was not influenced by the two agents, either alone or in
      combination, even when they were applied at their lowest efficacious doses or at
      higher cytotoxic doses. Experiments in vivo with the chick embryo chorioallantoic
      membrane (CAM)-sponge assay revealed the same dose-dependent inhibition and
      synergy. As the basic fibroblast growth factor (bFGF)-induced angiogenesis in the
      CAM-sponge model was strongly inhibited by the combined treatment, TNP-470 and
      rhIFN-alpha2a would appear to exert antiangiogenesis synergistically, perhaps by
      interfering with the bFGF-mediated pathway.

PMID- 10929038
TI  - The polyneuropathy associated with Waldenstrom's macroglobulinaemia can be
      treated effectively with chemotherapy and the anti-CD20 monoclonal antibody
      rituximab.
AB  - A 50-year-old male developed headache, impaired balance, visual defects and
      severe deafness. Ten months later he presented with markedly reduced power and
      tremor of his right arm. Waldenstrom's macroglobulinaemia (WM) with accompanying
      polyneuropathy was diagnosed. The patient received chemotherapy, which resulted
      in a partial improvement of the arm tremor. Subsequently, he was treated with
      rituximab (4 x 375 mg/m2), leading to complete resolution of the tremor and the
      paresis of his arm. Additionally, his headache and imbalance disappeared. Fifteen
      months after rituximab therapy he remained free of any neurological symptoms.
      This is the first report showing that WM-associated polyneuropathy can be treated
      effectively with a combination of chemotherapy and the anti-CD20 monoclonal
      antibody rituximab.

PMID- 10929039
TI  - Genetic instability in myelodysplastic syndrome: detection of microsatellite
      instability and loss of heterozygosity in bone marrow samples with karyotype
      alterations.
AB  - Using a polymerase chain reaction (PCR)-based approach, we examined the
      prevalence of loss of heterozygosity (LOH) and microsatellite instability (MSI)
      in relation to chromosomal imbalances in myelodysplastic syndrome (MDS). Two of
      26 patients displayed MSI (8%), one of them at five loci. LOH was detected in six
      out of 26 cases (23%), predominantly involving markers IRF1 [5q31] and WT1 [11p].
      Two patients displayed a corresponding chromosomal deletion by conventional
      cytogenetics. Supporting the mutator phenotype hypothesis, a significant
      coincidence of LOH, MSI and chromosome abnormalities was observed (P < 0.025).
      Moreover, our data suggest that LOH represents an initial rather than a secondary
      genetic event in MDS, promoting genetic instability in a subset of patients.

PMID- 10929040
TI  - Respiratory failure during induction chemotherapy for acute myelomonocytic
      leukaemia (FAB M4Eo) with ara-C and all-trans retinoic acid.
AB  - We report two cases of acute myeloid leukaemia FAB classification M4Eo with high
      white cell counts at presentation, who developed acute respiratory failure with
      pulmonary infiltrates on chest radiograph soon after commencing conventional
      cytotoxic chemotherapy plus all-trans retinoic acid (ATRA). We suggest that in
      patients with M4Eo ATRA should be used with caution, perhaps delaying its
      commencement until the white cell count is < 10 x 109/l.

PMID- 10929041
TI  - Porcine von Willebrand factor and thrombin induce the activation of c-Jun amino
      terminal kinase (JNK/SAPK) whereas only thrombin induces activation of
      extracellular signal-related kinase 2 (ERK2) in human platelets.
AB  - The interaction of platelets with subendothelial von Willebrand factor (VWF),
      especially under high shear stress, is considered to be the first activation step
      which primes platelets for subsequent haemostatic events. The signalling cascade
      which results from the interaction of VWF and its receptor GPIbIX has only been
      partially defined. Mitogen-activated protein kinases (MAPKs) are a family of
      downstream transmembrane signalling serine-threonine kinases and have been
      demonstrated to be present and functional in platelets; these include the
      extracellular signal-related kinases (ERKs), c-Jun amino-terminal kinases (JNKs)
      and p38 MAPK. Previously, we showed that p38 MAPK was not required in VWF-induced
      human platelet activation. It is not known whether VWF-dependent platelet
      activation involves the activation of the JNK and ERK family of signalling
      molecules. This report demonstrates that porcine von Willebrand factor (pVWF)
      induced a sustained and stable JNK activation measurable by 1 min after
      activation. Thrombin also induced JNK activation assessed at 1 min after
      activation. In contrast to thrombin, pVWF did not induce ERK2 activation at any
      time point tested. To ensure that ERK activation was unnecessary for pVWF
      dependent platelet activation, we functionally inhibited ERK-dependent signalling
      with PD98059, a potent and selective inhibitor of the MAP kinase kinase (MEK-1),
      which is the upstream kinase of ERK1 and ERK2. Although PD98059 inhibited ERK2
      activation in platelets, it had no effect on pVWF- or thrombin-induced platelet
      alpha or lysozomal granule release, modulation of membrane glycoprotein CD41,
      microparticle formation, platelet shape change or platelet agglutination. It is
      concluded that pVWF and thrombin induced JNK activation, but whereas thrombin
      induced ERK2 activation VWF did not; functional ERK2 activity was also not
      required for pVWF- or thrombin-dependent platelet activation.

PMID- 10929042
TI  - Role of A and B blood group antigens in the expression of adhesive activity of
      von Willebrand factor.
AB  - ABO (H) blood group antigens are covalently linked to the oligosaccharide side
      chains of von Willebrand factor (VWF). In this study, we investigated the role of
      the A and B antigens in the expression of VWF adhesive activity. VWF of type A, B
      or O was purified from fresh frozen plasma. Presence of A or B antigen on the VWF
      was confirmed by enzyme-linked immunosorbent assay (ELISA) and by immunoblotting
      with monoclonal anti-A or anti-B. The A or B antigen was also detected in the
      48/52-kDa fragment of the respective VWF after trypsin digestion. Removal of A
      antigen with alpha-N-acetylgalactosaminidase or B antigen with alpha
      galactosidase did not affect its multimer size or antigenic level, but decreased
      the ristocetin cofactor (RCoF) activity of the respective VWF by 33-39% (P < 0.01
      0.002). Removal of A or B antigen from VWF did not affect the binding of the VWF
      to immobilized type III collagen. A and B antigens were not detected in platelet
      VWF. These results indicate that AB structures play a role in platelet
      aggregating activity of VWF.

PMID- 10929043
TI  - Desmopressin: therapeutic limitations in children and adults with inherited
      coagulation disorders.
AB  - Desmopressin (DDAVP), a synthetic analogue of vasopressin has been successfully
      used in the treatment of type I von Willebrand's disease (VWD), mild factor VIII
      (FVIII) deficiency and intrinsic platelet function defects (PFDs) for almost
      three decades. However, there is limited published data documenting its efficacy
      and the reliability of circulating plasma FVIII:C as a surrogate marker of
      response to therapy in VWD. We report the haemostatic response to DDAVP in 133
      consecutive patients (91 type I VWD, 20 mild FVIII deficiency and 22 PFDs).
      Minimal therapeutic response to DDAVP (0.3 microg/kg) was defined by
      normalization 30 min post- infusion of bleeding time for PFDs, factor VIII:C
      (FVIII:C) for mild haemophilia A, and von Willebrand factor antigen (VWF:Ag), von
      Willebrand factor functional activity (VWF:Ac) and FVIII:C for VWD. Nine out of
      91 (10%) VWD patients failed to achieve minimal therapeutic response to DDAVP;
      plasma FVIII:C levels were an unreliable surrogate marker of DDAVP response as 6
      out of 9 (67%) of these patients had normal post-infusion FVIII:C levels. Five
      out of the 20 (25%) patients with mild FVIII deficiency and 5 out of 22 (23%)
      patients with PFDs failed to achieve a minimal therapeutic response to DDAVP.
      DDAVP is an effective therapy in the majority of patients with type I VWD, PFDs
      and mild FVIII deficiency. The significant failure rate associated with this
      therapy supports the recent recommendations that response should be assessed in
      all patients at the time of diagnosis. FVIII:C is an unreliable guide of response
      to DDAVP in patients with VWD and therefore VWF:Ag and VWF:Ac should also be
      assessed. Failure to demonstrate the response of VWF:Ag, VWF:Ac and FVIII:C to
      DDAVP in patients with VWD is likely to increase the risk of haemorrhagic
      complications in patients with bleeding episodes or who are undergoing surgery.

PMID- 10929044
TI  - Prevalence of methylenetetrahydrofolate reductase C677T and its association with
      arterial and venous thrombosis in the Chinese population.
AB  - Moderate hyperhomocysteinaemia (MHH) is associated with arterial and venous
      thrombosis. A main genetic defect related to MHH is a C to T substitution at
      nucleotide 677 of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. A
      prothrombin 20210A mutation was recently identified as a risk factor for arterial
      and venous thrombosis. However, studies on the prevalence of mutant MTHFR C677T
      and prothrombin G20210A and their association with thrombosis were controversial
      and seldom reported in the Chinese population. We investigated the prevalence of
      MTHFR C677T and prothrombin G20210A genotypes by polymerase chain reaction (PCR)
      followed by restriction enzyme digestion in 420 Chinese subjects: 53 with deep
      venous thrombosis (DVT); 145 with cerebrovascular disease [115 cerebral
      infarction, 30 cerebral haemorrhage (CH)]; 100 with coronary artery disease
      (CAD); and 122 control subjects. The prevalence of the mutated MTHFR 677TT
      genotype and the 677T allele in normal controls was 12.3% and 30.7% respectively,
      similar to that in Caucasians and Japanese. The mutant 677T homozygotes and
      alleles were more frequent in patients with DVT than in controls (18.9% vs.
      12.3%, 0.01 < P < 0. 025; 48.1% vs. 30.7%, P < 0.005). The relative risk of DVT
      among the carriers of 677TT and 677T were significantly increased [odds ratios:
      3.4, 95% confidence interval (CI) 1.3-9.5, and 3.6, 95% CI 1. 7-7.7,
      respectively). The mutant MTHFR heterozygous 677C/T carriers were increased in
      patients with cerebral infarction compared with controls (53.9% vs. 36.9%, 0.01 <
      P < 0.025). Relative risk of cerebral infarction was 0.96 (95% CI 0.4-2.3) for
      677TT homozygotes and 1.99 (95% CI 1.2-3.4) for 677C/T heterozygotes. However,
      the distribution of the MTHFR TT genotype was less frequent in patients with CAD
      with coronary artery stenosis of > 50% than in controls (2. 8% vs. 12.3%, 0.025 <
      P < 0.05). Relative risk of CAD was not increased among the carriers of 677TT and
      677T (odds ratios: 0.2, 95% CI 0-1.1, and 0.97, 95% CI 0.5-1.8, respectively).
      There were no differences in the distribution of the MTHFR genotypes among CH,
      CAD with coronary artery stenosis of < 50% and controls. The prothrombin 20210A
      mutation was not found in any patients or controls. These results demonstrated
      that MTHFR 677T was associated with DVT and cerebral infarction but was less
      associated with CAD in the Chinese population.

PMID- 10929045
TI  - Inhibition of complement-mediated haemolysis in paroxysmal nocturnal
      haemoglobinuria by heparin or low-molecular weight heparin.
AB  - Complement (C')-mediated haemolysis in paroxysmal nocturnal haemoglobinuria (PNH)
      is mainly due to the deficiency of glycosyl phosphatidylinositol-anchored
      membrane proteins with C'-regulatory activities CD55 and CD59 in PNH-affected red
      blood cells (RBCs). Hydrophobic insertion of C5b-7 to RBC membranes, initiating
      the formation of a membrane attack complex, readily results in lysis of PNH RBCs
      due to the deficiency of CD59. We studied the significance of the electrostatic
      interactions between C5b-6 and RBC membranes preceding the insertion of C5b-7. In
      vitro, C'-mediated lysis of PNH RBCs (assessed by sucrose haemolytic assay) was
      inhibited by heparin, low-molecular weight heparin (LMWH) or protamine,
      indicating the significance of the electrostatic interactions between C'
      components and RBC membranes in the process of C'-mediated haemolysis.
      Neuraminidase-treated PNH RBCs became resistant to C' activation, suggesting that
      the sialic acid moieties on RBC membranes are involved in the interactions of RBC
      with C' components. By using biotin-labelled C7, we demonstrated that LMWH as
      well as heparin inhibited the insertion of C5b-7 to RBCs, although they did not
      inhibit the incorporation of C7 into membrane-associated C5b-6. Neither heparin
      nor LMWH could inhibit the procoagulant alteration of PNH RBC membranes induced
      by C' activation even at concentrations which inhibited the haemolysis
      completely. Because LMWH inhibited the C'-mediated lysis of PNH RBCs in vitro at
      the range which induced a limited prolongation of activated partial
      thromboplastin time of normal plasma, we consider that LMWH may be useful for
      both the inhibition of haemolysis and the prevention of thrombosis, which often
      follow a haemolytic attack in PNH.

PMID- 10929046
TI  - Functional effects of replacing human alpha- and beta-globins with their
      embryonic globin homologues in defined haemoglobin heterotetramers.
AB  - Embryonic- and adult-stage globin subunits assemble into haemoglobin (Hb)
      heterotetramers that are expressed at low levels throughout human intrauterine
      development. These haemoglobins differ from adult Hb A (alpha2beta2) by the
      substitution of embryonic zeta for adult alpha globin (Hb zeta2beta2), or
      embryonic epsilon for adult beta globin (Hb alpha2epsilon2). Several key
      physiological properties of these 'semiembryonic' haemoglobins remain undefined,
      as ethical and methodological considerations have limited their availability from
      both human sources and conventional expression systems. The current study
      attempts to estimate how the physiological properties of semiembryonic and adult
      haemoglobins may differ, by determining whether the O2-binding characteristics of
      hybrid human/mouse haemoglobins change when human alpha- or beta-globin subunits
      are replaced by human embryonic zeta- or epsilon-globin subunits respectively.
      Each of the four human globins is expressed in transgenic mice that are
      nullizygous for either the endogenous mouse alpha- or beta-globin genes,
      resulting in the high-level expression of haemoglobins that can be studied either
      in situ in intact erythrocytes or in vitro. We showed that the exchange of human
      zeta-globin for human alpha-globin chains increased haemoglobin O2 affinity, both
      in the presence and in the absence of 2, 3-bisphosphoglycerate (2,3-BPG), and
      reduced the pH-dependent shift in its oxygen equilibrium curve (Bohr effect). By
      comparison, hybrid haemoglobins containing either human epsilon-globin or human
      beta-globin exhibited nearly identical O2-binding properties, both in situ and in
      vitro, regardless of 2,3-BPG levels or ambient pH. Neither the zeta-for-alpha nor
      the epsilon-for-beta substitutions substantially altered binding affinity for 2,3
      BPG or cooperativity between globin subunits. These studies suggest that
      semiembryonic haemoglobins that assemble entirely from human subunits may exhibit
      properties that are similar to those of human Hb A.

PMID- 10929047
TI  - Performance of the OptiMAL malaria antigen capture dipstick for malaria diagnosis
      and treatment monitoring at the Hospital for Tropical Diseases, London.
AB  - We report here the sensitivity and specificity of OptiMAL for the diagnosis of
      acute malaria in patients presenting to the Hospital for Tropical Diseases (HTD),
      a tertiary referral centre for Tropical and Infectious diseases. A sensitivity of
      95.3% and a specificity of 100% for Plasmodium falciparum and a sensitivity of
      96% and a specificity of 100% for Plasmodium vivax was obtained. The ability to
      follow the course of the parasitaemia using OptiMAL during treatment and its
      significance for use in areas where expert microscopy is not available is
      discussed.

PMID- 10929048
TI  - Fortifying B cells with CD154: an engaging tale of many hues.

PMID- 10929050
TI  - Regulation of T-cell apoptosis: a mixed lymphocyte reaction model.
AB  - Despite the capacity for antigen-specific activation and rapid clonal expansion,
      homeostatic mechanisms ensure that the mature immune system contains a relatively
      stable number of T cells. In recent years, it has become apparent that this
      stability is a consequence of apoptotic death of most of the specific T cells
      generated during an immune response. Clearly this process must be tightly
      regulated in order to retain sufficient T-cell progeny to mediate an effective
      response, whilst allowing the rapid deletion of these cells at the end of the
      response to prevent lymphadenopathy and cross-reactive autoimmunity. In this
      study, the factors that regulate the sensitivity of T cells to apoptosis were
      investigated in vitro after the induction of primary T-cell activation within a
      mixed lymphocyte reaction (MLR). It was found that activated T cells rapidly
      acquire the expression of both Fas and Fas ligand (FasL) on their surface and
      contain high levels of the precursor form of the pro-apoptotic enzyme, caspase 8
      (FLICE). However, these T cells were resistant for up to 5 days to apoptosis
      following the stimulation of Fas; a maximal apoptotic response was observed after
      7 days. This time point coincided with a marked reduction in expression of the
      FLICE inhibitory protein (FLIP) and maximal activity of caspase 8. At time points
      beyond day 7, the number of viable cells in the MLR decreased further despite a
      reduction in the expression of FasL. However, the expression of interleukin-2 (IL
      2) at these late time points was low, resulting in a decrease in expression of
      the anti-apoptotic protein Bcl-2. This can produce apoptosis by allowing leakage
      of cytochrome-c from mitochondria resulting in direct activation of the caspase
      cascade. In this study, it is shown that T cells are resistant to apoptosis for
      the first 5 days after activation as a consequence of insensitivity of the Fas
      pathway and the presence of intracellular Bcl-2. After between 5 and 7 days, the
      cells become sensitive to Fas-mediated apoptosis while retaining Bcl-2
      expression. At later time points, Fas ligation is reduced but the cells respond
      to a decreased availability of IL-2 by reducing Bcl-2 expression; this encourages
      further apoptosis by allowing the direct activation of caspase enzymes.

PMID- 10929049
TI  - T-cell regulation of peripheral tolerance and immunity: the potential role for
      Notch signalling.
AB  - Recognition of antigen by T cells in the periphery may lead either to the
      generation of productive immunity or the induction of tolerance. These two
      functional outcomes are a consequence of distinct pathways of T-cell
      differentiation. T cells are selected to become regulatory cells and their
      function is to maintain homeostasis with the immune system. In this review we
      discuss the cell-fate decisions that T cells might make allowing them to promote
      immunity or induce tolerance in the context of the role that Notch signalling may
      play in this process.

PMID- 10929051
TI  - Evidence for a unique expression of CD4 on murine vaginal CD4+ cells.
AB  - Mucosal cell-mediated immunity (CMI) by CD4+ T cells is postulated to be
      important for host defence against several vaginal pathogens. In addition to the
      recognized phenotypic distinctions of resident vaginal T lymphocytes, we recently
      provided evidence by fluorescence-activated cell sorter (FACS) that murine
      vaginal CD4+ T lymphocytes, are differentially recognized by two epitope-distinct
      anti-CD4 antibodies, suggesting that the CD4 protein on vaginal CD4+ cells is
      atypically expressed. In the present study, we confirm this by FACS and
      immunohistochemistry under non-denaturing conditions using two additional anti
      CD4 antibodies. However, positive immunohistochemical staining of vaginal CD4+
      cells under denaturing conditions revealed that the CD4 epitope in question is
      indeed present within the CD4 protein. Using reverse transcription polymerase
      chain reaction, amplification of CD3, T-cell receptor-beta (TCR-beta), and TCR
      delta mRNA from lymph node and vaginal tissue, and CD4 mRNA from lymph node
      tissue was demonstrable. In contrast, amplification of CD4 mRNA from vaginal
      tissue, vaginal enriched lymphoid cells, or a purified (FACS-sorted) population
      of vaginal-specific CD4+ cells using two distinct primer sets was not
      demonstrable. Altogether, our results provide evidence that the CD4 protein on
      vaginal CD4+ T cells is conformationally distinct compared with its systemic
      counterpart, either as a result of a unique CD4 mRNA sequence or from a stable
      interaction of soluble CD4 with the surface of vaginal T cells.

PMID- 10929052
TI  - Impaired delayed-type hypersensitivity response in mutant mice secreting soluble
      CD4 without expression of membrane-bound CD4.
AB  - Delayed-type hypersensitivity (DTH) is an important in vivo manifestation of cell
      mediated immunity. We examined the DTH response to methylated bovine serum
      albumin of a novel mutant strain of mice that have soluble CD4 (sCD4) in their
      circulation without expression of CD4 on the cell surface. The DTH response of
      the mutant mice was severely impaired, although the response of CD4 knockout (KO)
      mice, generated by homologous recombination, was comparable to that of wild-type
      mice. The response of the mutant mice was restored by the neutralization of sCD4
      with anti-CD4, and that of CD4KO mice was markedly reduced by the implantation of
      a diffusion chamber containing sCD4 cDNA transfectant cells. The restored DTH
      response of the mutant mice treated with anti-CD4 was abolished by treatment with
      anti-interferon-gamma (IFN-gamma). IFN-gamma production by CD4 mutant and CD4KO
      mice was consistent with their DTH response and inversely related to the presence
      of sCD4 in their circulation, indicating that sCD4 impairs the DTH response by
      blocking the production of IFN-gamma in our mutant mice. These results raise the
      possibility that sCD4 could impair cell-mediated immunity. Our mutant mice would
      provide a useful tool with which to analyse the mechanisms of the DTH reaction.

PMID- 10929053
TI  - Mouse xenoantigens contribute to rat T-cell Vbeta repertoire generation in mixed
      xenogeneic bone marrow chimeras.
AB  - We previously demonstrated that rat bone-marrow-derived cells in mixed xenogeneic
      chimeras (rat + mouse --> mouse) contribute to peripheral selection of mouse T
      cell receptor (TCR) variable betas (Vbetas) repertoire. In this study, we
      analysed rat T cells that developed in the chimeras to assess the contribution of
      mouse xenoantigens to the development of rat TCR repertoire. The expression of
      rat Vbetas was analysed using flow cytometry and a reverse transcription
      polymerase chain reaction (RT-PCR) method that allows for both semiquantitative
      analysis of rat Vbeta gene expression and size heterogeneity of the
      complementarity determining region 3 (CDR3) domain. Three distinct patterns of
      Vbeta expression were detected. Partial deletion was observed for Vbeta5, 7, 12,
      14, 16, 17 and 20 that exhibited reduced levels of peripheral expression by 3.4-,
      1.8-, 8.7-, 2.0-, 7.8-, 9.5- and 1.8-fold, respectively, compared with the levels
      of Vbetas in naYve rats. Higher levels of peripheral expression were detected for
      three rat Vbeta genes; Vbeta6 (2.2-fold), Vbeta8.2 (3.2-fold), and Vbeta9 (1.7
      fold). The relative expression of the other 10 known rat Vbeta families in
      chimeras was unchanged as compared with that of normal rats. We did not observe
      detectable changes in the pattern of CDR3 expression in chimeras, suggesting that
      the mouse xenogeneic environment exerted its influence on the development of rat
      T cells via the Vbeta-encoded CDR1/2 domains. Our data demonstrate that the rat T
      cell repertoire in chimeras is shaped by both contractions as well as expansions
      of selected Vbetas and suggest that mouse xenoantigens and/or superantigens of
      endogenous mouse retroviruses may contribute as ligands for these selection
      processes

PMID- 10929054
TI  - Tolerance and bystander suppression, with involvement of CD25-positive cells, is
      induced in rats receiving serum from ovalbumin-fed donors.
AB  - In the present study we have investigated if transfer of serum from rats fed
      ovalbumin (OVA) leads to specific tolerance and bystander suppression in
      recipient animals. Rats that received serum from OVA-fed donors had a lower
      delayed-type hypersensitivity reaction (DTH) both against OVA and the bystander
      antigen, human serum albumin (HSA), compared with recipients given serum from
      control-fed animals. The in vitro proliferation of OVA- and HSA-stimulated spleen
      cells and the serum immunoglobulin G (IgG) antibody levels against OVA and HSA
      were also lower in the animals that received serum from OVA-fed animals compared
      with the controls. There was no reduction of the immune response to HSA if the
      recipient animals, given serum from OVA-fed donors were immunized with OVA and
      HSA at separate sites. Depletion of CD25-positive cells from spleen suspensions
      from rats receiving serum from OVA-fed animals, resulted in a significant
      increase in proliferation of OVA-stimulated cells in vitro compared with the
      controls. Tolerogenic activity could be demonstrated, both in a fraction from
      serum containing structures smaller than 100 000 MW and a fraction with
      components larger than 100 000 MW, compared with size-related serum fractions
      obtained from control-fed animals. This implies that the tolerogenic activity
      could be mediated by more than one serum component. The tolerogenic activity was
      most prominent in animals receiving the larger size fraction with a more
      pronounced suppression of the DTH reaction and lower levels of IgG anti-OVA
      antibodies in serum compared with controls. A novel finding in the present study
      was that the transfer of serum, collected from rats fed OVA, led to a reduction
      of the immune response to a bystander antigen in the recipients. This suggests
      that the induced tolerance is at least partly due to suppression. The suppression
      could have been mediated by CD25-positive cells since removal of these cells
      resulted in an increased in vitro proliferation against OVA.

PMID- 10929055
TI  - A monoclonal antibody to the rat Crry/p65 antigen, a complement regulatory
      membrane protein, stimulates adhesion and proliferation of thymocytes.
AB  - A murine monoclonal antibody (mAb), 3F10, was produced by fusion of spleen cells
      obtained from mice immunized with a rat cortical thymic epithelial cell line (R
      TNC.1) stimulated with interferon-gamma and P3X myeloma cells. 3F10 recognized an
      antigen expressed both on thymocytes and non-lymphoid cells in the thymus. Flow
      cytometry showed that 3F10 stained more than 98% thymocytes and 90% R-TNC.1
      cells. Immunoprecipitation and Western blot studies demonstrated that 3F10
      reacted with molecules of 55000 and 65000 MW from both thymocyte and R-TNC.1 cell
      lysates. 3F10 recognized the same antigen on Chinese hamster ovary cells
      transfected with rat Crry as did 5I2 mAb, confirming the specificity of 3F10 mAb
      for the rat homologue of mouse Crry/p65, a membrane-bound complement regulatory
      protein. 3F10 mAb induced homotypic aggregation of thymocytes and exhibited an
      additive effect on the aggregation evoked by phorbol myristate acetate. The
      aggregation was dependent on active cell metabolism, intact cytoskeleton,
      divalent cations and activation of protein phosphatases 1 and 2A (as assessed by
      use of okadaic acid). In contrast, H-7, HA1004 and genistein partially inhibited,
      whereas staurosporine potentiated the aggregation of thymocytes triggered by
      3F10. 3F10 mAb also stimulated binding of thymocytes to the R-TNC.1 line. Both
      homotypic and heterotypic adhesive interactions are mediated by leucocyte
      function-associated antigen-1 (LFA-1). In addition, 3F10 stimulated proliferation
      of thymocytes induced by suboptimal concentrations of concanavalin A. These data
      suggest that rat Crry/p65 might be involved in the regulation of both cell
      adhesion and activation of thymocytes. This is a novel, non-complement-dependent
      function of Crry/p65.

PMID- 10929056
TI  - Induction of interactions between CD44 and hyaluronic acid by a short exposure of
      human T cells to diverse pro-inflammatory mediators.
AB  - Migration of T cells into extravascular sites of inflammation is mediated by cell
      cell and cell-matrix adhesion receptors, including the hyaluronan-binding
      glycoprotein, CD44. The biochemical nature of CD44 variants and the ligand
      specificity, function and the regulation of activation of CD44 expressed on
      various cell types have been extensively studied. However, little is still known
      about the short-term influence of cytokines and chemokines on the activation of
      CD44 on human T cells. Therefore, we studied the role of inflammatory mediators
      in regulating the adhesion of T cells from human peripheral blood to immobilized
      hyaluronan under static or shear stress conditions. We found that the CD44
      dependent adhesion, under static and shear stress (i.e. relative gradual
      resistance to flow of 150 and 1500 s-1) conditions, of T cells to hyaluronan
      requires a T-cell activation of 2-3 hr and is regulated by the cross-linking of
      CD3, cytokines (e.g. interleukin-2 and tumour necrosis factor-alpha), and
      chemokines (e.g. MIP-1beta, interleukin-8, and RANTES). This T-cell adhesion was
      manifested by polarization, spreading and co-localization of cell surface CD44
      with a rearranged actin cytoskeleton in hyaluronan-bound T cells. Thus, cytokines
      and chemokines present in the vicinities of blood vessel walls or present
      intravascularly in tissues where immune reactions take place, can rapidly
      activate the CD44 molecules expressed on T cells.

PMID- 10929057
TI  - Inflammatory cytokine production by immunological and foreign body multinucleated
      giant cells.
AB  - Multinucleated giant cells (MGC) are a common feature of granulomas. The
      mechanism of their formation has been studied extensively, but their function has
      not been completely characterized. A new method for the in vivo production of MGC
      was developed involving subcutaneous injection of microscopic nitrocellulose
      particles with adsorbed mycobacterial antigens into the footpads of sensitized
      BALB/c mice (immune [I]-MGC), or by nitrocellulose administration to non
      sensitized mice (foreign body [FB]-MGC). The development of granulomas with a
      highly enriched MGC population was observed 2 weeks after the nitrocellulose
      injection. MGC were larger with a greater number of nuclei in I-MGC than in FB
      MGC. From days 7-28 after nitrocellulose administration, the production of
      interleukin-1alpha (IL-1alpha) and tumour necrosis factor-alpha (TNF-alpha) was
      demonstrated in both MGC types by in situ reverse transcription-polymerase chain
      reaction (RT-PCR) and immunohistochemistry. After 2 months, the MGC had ceased
      production of IL-1alpha and TNF-alpha, but the expression of transforming growth
      factor-beta (TGF-beta) was very high, occurring together with extensive fibrosis.
      These results suggest that MGC are an active source of inflammatory cytokines,
      which can contribute to the initiation, maintenance and down-regulation of
      granulomatous inflammation induced by immunological and inert substances.

PMID- 10929058
TI  - Adrenaline inhibits macrophage nitric oxide production through beta1 and beta2
      adrenergic receptors.
AB  - This study was conducted to investigate the role of the acute stress hormone
      adrenaline on macrophage nitric oxide (NO) production. Murine peritoneal
      macrophages were stimulated in vitro with lipopolysaccharide (LPS) in the absence
      or presence of adrenaline. Adrenaline inhibited the LPS-induced nitrite response
      in a dose-dependent manner. The suppressive effect of adrenaline on NO production
      was mediated via beta1 and beta2 adrenergic receptors since isoprenaline (a non
      selective beta1 and beta2 agonist), dobutamine and salbutamol (selective beta1
      and beta2 agonists, respectively) had similar effects on the NO response. In
      addition, the inhibitory effect of adrenaline on NO was abrogated by both
      propranolol (a non-specific beta blocker) and atenolol (a specific beta1
      inhibitor). In contrast to beta receptor activation, the alpha adrenergic agonist
      phenylephrine had no effect on the LPS NO response, and furthermore, phentolamine
      (an alpha receptor antagonist) did not ameliorate adrenaline's inhibitory action.

PMID- 10929059
TI  - Comparative analysis of integrin expression on monocyte-derived macrophages and
      monocyte-derived dendritic cells.
AB  - Both macrophages (MAC) and dendritic cells (DC) are members of the mononuclear
      phagocyte system (MPS) with monocytes (MO) as common precursor cells. Cells of
      the MPS are able to take up, process and present antigens to T lymphocytes,
      thereby inducing a primary or secondary immune response. Adhesion molecules are
      of crucial importance for the interaction of antigen-presenting cells with immune
      cells, especially T lymphocytes. By representational difference analysis, we
      identified CD49c (VLA-3), a member of the beta1-integrin family of adhesion
      receptors, as differentiation-associated antigen in MO-derived MAC. In contrast,
      MO-derived DC did not express CD49c mRNA. These data prompted us to compare the
      integrin expression pattern of MAC and DC. Both cell types showed a low
      expression of the alpha-chains of the beta1-integrins CD49a, CD49b, CD49d and
      CD49e, whereas a marked difference was observed for CD49c and CD49f. Expression
      of both integrins increased during MO to MAC differentiation, but was not
      detectable on DC. In parallel the beta1-chain (CD29) was clearly up-regulated
      during MO to MAC differentiation but was only weakly expressed on DC. On the
      other hand, the beta2-integrins CD11a, CD11b, CD11c and CD18 were all expressed
      on MAC and DC. Beside their role in cell-cell interaction and adhesion, beta2
      integrins are also known as possible binding molecules for bacteria and
      lipopolysaccharide (LPS), especially for high LPS concentrations. Therefore we
      investigated the LPS response of MAC versus DC in terms of tumour necrosis factor
      alpha (TNF-alpha) release. DC were less responsive to low doses of LPS, which can
      easily be explained by the very low CD14 expression on DC compared for MAC. In
      contrast, the TNF-alpha response was comparable to MAC when DC were stimulated
      with high LPS concentrations. Our results show a specific, differentiation
      dependent pattern of beta1- and beta2-integrin expression on in vitro-generated
      MAC and DC. We suggest that the high expression of CD11/CD18 on DC could be
      involved in the LPS binding of DC. As LPS is not only an activation but also a
      differentiation stimulus for DC, the expression of CD11/CD18 on DC may be
      important for the successful maturation of DC and thereby the initiation of a
      primary immune response.

PMID- 10929060
TI  - SHP-1/immunoreceptor tyrosine-based inhibition motif-independent inhibitory
      signalling through murine natural killer cell receptor Ly-49A in a transfected B
      cell line.
AB  - Ly-49A is a member of the Ly-49 family of mouse natural killer cell receptors
      that inhibit cytotoxicity upon recognition of their ligands, the major
      histocompatibility complex (MHC) class I molecules, on the target cell surface.
      Although Ly-49A has an immunoreceptor tyrosine-based inhibition motif (ITIM) in
      its cytoplasmic tail, relatively little is known about the mechanisms underlying
      its inhibitory function. We report here that antibody-mediated co-ligation of the
      B-cell receptor (BCR) with the transfected Ly-49A molecule results in abrogation
      of BCR-induced interleukin-2 (IL-2) secretion and mild reduction in activation of
      Erk1/2 and p38 mitogen-activated protein (MAP) kinases in the B-cell line A20.
      Surprisingly, BCR-induced calcium mobilization was unaffected by cross-linking of
      BCR with Ly-49A. Furthermore, substitution of the single tyrosine residue in ITIM
      with phenylalanine, did not result in a complete loss of inhibitory function, as
      measured by BCR-induced IL-2 secretion. Deletion of the N-terminal 37 amino acid
      peptide, which includes the ITIM, did abrogate the inhibitory activity. Co
      immunoprecipitation experiments revealed that, upon induction of tyrosine
      phosphorylation, Ly-49A recruits tyrosine phosphatase src-homology 2 (SH2)
      containing tyrosine phosphatases-1 (SHP-1), but not inositol phosphatase src
      homology 2 (SH2) containing inositol phosphatase (SHIP), and that the tyrosine
      residue in the ITIM is critical for this interaction. These results suggest that
      transfected Ly-49A utilizes two different inhibitory mechanisms in B-cell
      signalling: ITIM-dependent and ITIM-independent.

PMID- 10929061
TI  - 2B4 stimulation of YT cells induces natural killer cell cytolytic function and
      invasiveness.
AB  - 2B4 is a surface molecule found on all human natural killer (NK) cells, a subset
      of CD8+ T cells, monocytes and basophils. It was originally identified on mouse
      NK cells and the subset of T cells that mediate non-major histocompatibility
      complex (MHC)-restricted killing. Recently,9 we have cloned the human homologue
      of 2B4 (h2B4) and found h2B4 to also mediate non-MHC-restricted cytotoxicity. In
      this study, we examine h2B4 in regulating various functions of NK cells using a
      human NK cell line YT, with monoclonal antibody (mAb) C1.7, an antibody that
      specifically recognizes h2B4. Ligation of surface 2B4 with mAb C1.7 increases
      YT's ability to destroy tumour cells. In the presence of mAb C1.7, the production
      of interferon-gamma (IFN-gamma) by YT cells is greatly enhanced. Engagement of
      surface 2B4 by mAb C1.7 downregulates the expression of h2B4 at the cell surface
      as well as the expression of h2B4 mRNA. Also, signalling through h2B4 causes the
      increased expression of matrix metalloproteinase-2, a member of the matrix
      degrading proteinase family. Thus, in addition to modulating cytolytic function
      and cytokine production of NK cells, activation through surface 2B4 may play a
      role in upregulating the machinery for degradation of extracellular matrices to
      promote invasion of the tumour by NK cells.

PMID- 10929062
TI  - Sex hormone levels correlate with the activity of cytokine-secreting cells in
      vivo.
AB  - This work examines the correlation between serum levels of oestrogen,
      progesterone and dehydroepiandrosterone sulphate (DHEA-S) and the number of human
      peripheral blood cells actively secreting interleukin (IL)-2, IL-4, IL-6, IL-10,
      tumour necrosis factor-alpha (TNF-alpha) or interferon-gamma (IFN-gamma) in vivo.
      Simultaneous assessment of serum hormone levels and cytokine-secreting cell
      activity throughout the menstrual cycle showed that the number of peripheral
      blood mononuclear cells (PBMC) able to secrete IL-4 in response to stimulation
      correlated significantly (P < 0.0001) with oestrogen levels and fluctuated with
      the menstrual cycle in pre-menopausal women. The activity of IFN-gamma-secreting
      cells, on the other hand, varied as a function of serum DHEA-S levels in pre
      menopausal women (P < 0.0001). Similarly, the number of cells secreting IFN-gamma
      in men correlated with serum DHEA-S levels (P < 0.001). In contrast, post
      menopausal women had fewer cells actively secreting cytokines and the activity of
      these cells did not correlate with sex hormone levels. These results suggest that
      sex hormones may modulate cytokine production in vivo and contribute to gender
      related differences in normal and pathological immune responses.

PMID- 10929063
TI  - Interactions between hormone-mediated and vaccine-mediated immunotherapy for
      pulmonary tuberculosis in BALB/c mice.
AB  - Problems of logistics, compliance and drug resistance point to an urgent need for
      immunotherapeutic strategies capable of shortening the current 6-month
      chemotherapy regimens used to treat tuberculosis, or of supplementing ineffective
      therapy. In this study we sought to define the mechanism of action of two
      immunotherapies, both of which have previously been shown to prolong survival.
      Secondly, we wished to identify any clinically useful synergy between these
      therapies. In BALB/c mice infected via the trachea with Mycobacterium
      tuberculosis H37Rv there is an initial phase of partial resistance dominated by
      type 1 cytokines plus tumour necrosis factor-alpha (TNF-alpha) and interleukin-1
      (IL-1), followed by a phase of progressive disease. This progressive phase is
      accompanied by increasing expression of IL-4, and diminished expression of IL-1
      and TNF-alpha. Animals in this late progressive phase of the disease (day 60)
      were treated with two injections (day 60 and day 90) of 0.1 or 1.0 mg of heat
      killed Mycobacterium vaccae, or with 3beta, 17beta-androstenediol (AED; 25 microg
      subcutaneously three times/week), or with both therapies. We show here using four
      techniques in parallel (morphometry, immunohistochemistry with automated cell
      counting, semiquantitative reverse transcription-polymerase chain reaction and
      enzyme-linked immunosorbent assays of cytokines in lung extracts) that treatment
      with M. vaccae causes a switch back towards a type 1 cytokine profile,
      restoration of expression of IL-1alpha and TNF-alpha, and a switch from pneumonia
      to granuloma. This is very similar to the changes previously seen after treatment
      with AED. However, there was no evidence for synergy between M. vaccae and AED.

PMID- 10929064
TI  - Lack of metallothionein-I and -II exacerbates the immunosuppressive effect of
      ultraviolet B radiation and cis-urocanic acid in mice.
AB  - The effect of a null mutation for the metallothionein (MT)-I and -II isoforms in
      mice on the immunosuppressive action of ultraviolet B (UVB; 280-320 nm) radiation
      has been examined. Mice were exposed to a series of increasing daily UVB doses,
      each dose administered to the dorsum on 3 consecutive days. Erythema was
      assessed, and measured as its oedema component by the post-irradiation dorsal
      skinfold thickness, but there was no effect of the null mutation (MT-/-) observed
      after 3 x 3.4 kJ/m2 of UVB radiation. Immune function was assessed by the contact
      hypersensitivity (CHS) response, which was initiated by sensitization on
      unirradiated abdominal skin, and thus demonstrated the systemic effects of dorsal
      treatments. In comparison with the wild-type MT+/+ mouse, the MT-/- mouse was
      significantly more immunosuppressed by moderate daily UVB doses (1. 75-5.9
      kJ/m2). When topically applied cis-urocanic acid (cis-UCA) replaced UVB radiation
      as the immunosuppressive agent, contact hypersensitivity in MT-/- mice was again
      markedly more suppressed than in MT+/+ mice, in a dose-responsive manner. The
      results infer that MT, which was shown immunohistochemically to be strongly
      induced in the epidermis of MT+/+ mice, but to be absent in MT-/- epidermis, has
      the potential to protect from photoimmunosuppression, and that the mechanism of
      action may be via the inactivation of the epidermal UVB-photoproduct, cis-UCA.

PMID- 10929066
TI  - Review article: ageing and the neutrophil: no appetite for killing?
AB  - In the armoury of the immune system developed to combat the various micro
      organisms that could invade the host, the neutrophil forms the first line of
      defence against rapidly dividing bacteria and fungi. However, as humans age they
      become more susceptible to infection with these microbes and this has been
      ascribed to a decline in immune status, termed immune senescence. Here we
      summarize the literature specifically concerning the attenuation of neutrophil
      function with age and the possible mechanisms underlying their reduced response
      to infectious agents.

PMID- 10929065
TI  - Review article: thymus organ cultures and T-cell receptor repertoire development.

PMID- 10929067
TI  - Presence of B220 within thymocytes and its expression on the cell surface during
      apoptosis.
AB  - B220 is the full-length splicing isoform of a tyrosine phosphatase CD45 and is
      predominantly expressed as a transmembrane protein on B cells. Other splicing
      isoforms of CD45 are yielded by alternative splicing of exons 4, 5 and 6.
      Recently, the expression of B220 on peripheral T cells during activation-induced
      cell death has been reported. To investigate whether B220 is implicated in
      apoptosis of immature T cells, we analysed (by flow cytometry using the anti-B220
      monoclonal antibody, RA3-6B2) the expression of B220 on mouse thymocytes
      undergoing X-irradiation- and dexamethasone (DEX)-induced apoptosis. The
      expression of B220 on thymocytes positive for Thy-1 was induced by X-irradiation
      or DEX treatment and increased with length of incubation. The expression of B220
      was pronounced on the apoptotic hypodiploid cells in the fraction showing lower
      forward scattering values. Reverse transcription-polymerase chain reaction
      detected mRNA containing exons 4, 5 and 6 of CD45 in normal thymocytes as well as
      those exposed to X-rays or DEX. Surprisingly, cytoplasmic B220 antigens were
      detected in a considerable fraction of normal thymocytes. Moreover, the
      expression level of the 220 000-MW protein in normal thymocytes was similar to
      that in the thymocytes undergoing apoptosis. During apoptosis, the expression
      level of B220 antigen was reduced in the cytoplasm but, conversely, up-regulated
      on the surface of thymocytes. These results suggest that B220 is constitutively
      expressed as a cytoplasmic form within thymocytes and possibly translocated to
      the cell membrane during apoptosis.

PMID- 10929068
TI  - Failure to remove autoreactive Vbeta6+ T cells in Mls-1 newborn mice attributed
      to the delayed development of B cells in the thymus.
AB  - Clonal deletion of autoreactive T cells in the thymus is one of the major
      mechanisms for establishing tolerance to self-antigens, and self-reactive T cells
      bearing Vbeta6 T-cell receptors are usually deleted before their maturation in
      Mls-1a mice. However, these T cells develop transiently in the neonatal thymus,
      and migrate to the periphery. In order to understand the mechanisms which permit
      these potentially auto-toxic T cells to generate, we investigated in vivo the
      physiological or functional properties of the elements involved, such as neonatal
      T cells, antigens and antigen-presenting cells (APC). Confirming the previous
      findings that each of these elements per se is already completed in function in
      neonates, we investigated the possibility of the absence or immaturity of
      particular APC with Mls antigens of their own products in the neonatal thymus. In
      the search for the cellular and histological changes occurring in the newborn
      thymus, we found that the elimination of Vbeta6+ T cells progressed in parallel
      with the development of thymic B cells. Involvement of B cells in purging the
      autoreactive T cells from the newborn thymus was shown by prevention of the
      deletion of Vbeta6+ T cells after the removal of B cells by the treatment of
      neonates with anti-immunoglobulin M antibodies. The restricted and stable
      expression of CD5 on the thymic B cells, but not on the splenic cells, suggests
      that these B cells are not postnatal immigrants from the periphery. Finally, it
      is concluded that the deficiency in the deletion of self-reactive T cells in the
      thymus of Mls-1a neonates is due to the delayed development of B cells.

PMID- 10929069
TI  - Induction of functional CD154 (CD40 ligand) in neonatal T cells by cAMP-elevating
      agents.
AB  - A deficiency of neonatal T lymphocytes to express CD154 antigen in response to
      ionomycin and phorbol 12-myrsistate 13-acetate (PMA) stimulation or after CD3
      cross-linking has been described. In the present report we describe that CD45RA+
      newborn cells are able to synthesize and express CD154 at similar or even higher
      levels than adult cells in response to ionomycin and cAMP-elevating agents which
      trigger the protein kinase A (PKA) -mediated metabolic pathway. Peak CD154
      protein concentrations in newborn cells were found between 4 and 8 hr after
      stimulation with ionomycin and dibutyryl cAMP. These agents, however, did not
      induce expression of the early activation antigen CD69. Surface levels of CD154
      did not correlate with specific mRNA concentration, indicating that dibutyryl
      cAMP up-regulates CD154 by acting at a post-transcriptional stage. The CD154
      antigen induced by PKA activation of newborn cells was functional, since upon
      binding to CD40 on B lymphocytes in the presence of interleukin-4 (IL-4), it
      promoted immunoglobulin heavy-class switching to IgE. We also found a different
      pattern of cytokine production between neonatal and adult CD4+ T cells. In
      response to ionomycin and dibutyryl cAMP, cord blood cells were more prone than
      adult lymphocytes to secrete the T helper type 2-derived immunosuppressive
      cytokines IL-4 and IL-10. Taking into account that the feto-maternal environment
      is rich in cAMP-elevating agents, the reduced risk of graft versus host disease
      associated with cord blood trasplantation, as compared with the risk with adult
      bone marrow cell transplants, may be due to the bias of neonatal cells to
      differentiate towards the T helper type 2 functional cell subset.

PMID- 10929070
TI  - Biological function of CD40 on human endothelial cells: costimulation with CD40
      ligand and interleukin-4 selectively induces expression of vascular cell adhesion
      molecule-1 and P-selectin resulting in preferential adhesion of lymphocytes.
AB  - The expression of adhesion molecules on vascular endothelial cells determines the
      pattern of migration and extravasation of leucocytes in inflammation and
      immunity. Here we show that costimulation with CD40 ligand (CD40L) and
      interleukin (IL)-4 (or IL-13) gives rise to a unique pattern of adhesion molecule
      expression by human umbilical vein endothelial cells (HUVEC). CD40 ligation alone
      enhanced expression of vascular cell adhesion molecule-1 (VCAM-1), intracellular
      adhesion molecule-1 (ICAM-1) and E-selectin whereas IL-4 and IL-13 increased
      expression of VCAM-1 and P-selectin but not ICAM-1 or E-selectin. When IL-4 and
      CD40L were combined there was an additional increase of both VCAM-1 and P
      selectin, but ICAM-1 and E-selectin were both inhibited. The combined effects of
      IL-4 and CD40L signalling were not the result of altered response kinetics,
      enhanced sensitivity of the endothelium, or increased expression of CD40 or the
      IL-4 receptor. The rise in VCAM-1 expression induced by combined IL-4 and CD40L
      stimulation was slower and more sustained than with tumour necrosis factor-alpha
      (TNF-alpha) and occurred only on a subset (75-80%) of the endothelial cell
      population compared to 100% with TNF-alpha. Costimulation with IL-4 and CD40L
      increased adhesion of T cells and B cells above levels obtained with either
      signal alone, but decreased adhesion of neutrophils. Furthermore, CD40 and IL-4
      synergistically increased IL-6 but decreased IL-8 production by HUVEC. These
      results show that interactions between IL-4 and CD40 on endothelial cells give
      rise to specific patterns of adhesion molecule expression and cytokine production
      that may have important implications for lymphocyte and neutrophil migration and
      function at sites of inflammation.

PMID- 10929071
TI  - Dimerization of major histocompatibility complex class I on the surface of THP-1
      cells stimulates the expression of inducible nitric oxide synthase and subsequent
      nitric oxide release.
AB  - We show that dimerization of major histocompatibility complex (MHC) class I on a
      human monocytic cell line, THP-1, induces nitric oxide (NO) synthesis. Cells
      cultured in the presence of a human MHC class I-specific monoclonal antibody
      produced significant amounts of NO after 72 hr. Reverse transcription-polymerase
      chain reaction and flow cytometry analysis revealed that the cells synthesized
      detectable levels of inducible NO synthase mRNA and protein. These effects were
      not seen after treatment with monovalent Fab fragments or Fc fragments of the
      same antibody, or after treatment with a control antibody. These data show a link
      between innate and acquired immune mechanisms mediated by NO and MHC class I.

PMID- 10929072
TI  - Genes predisposing to autoimmunity augment constitutive major histocompatibility
      complex class II-associated presentation of the self-antigen IgG2a in vivo.
AB  - The self-antigen IgG2ab is poorly presented to a gamma2ab 435-451-reactive I-Ad
      restricted T-cell hybridoma unless available in high concentrations or targeted
      to Fcgamma- or complement receptors. Environmental factors, probably the extent
      of microbial challenge, profoundly influence the constitutive gamma2ab/I-Ad
      presentation in IgCHb, H-2d mice. Here we report also a strong genetic impact.
      Constitutive presentation was highly efficient in spleen and thymus of (NZB x
      BXSB)F1 mice, which inherit a predisposition to develop lupus. Presentation
      correlated with disease progression and the serum levels of IgG2ab and IgG2ab
      complement factor 3 complexes. The finding that constitutive presentation was by
      far most efficient in males indicated that it was augmented by the Y chromosome
      linked autoimmune acceleration Yaa gene. In line with previous data for healthy
      mice, constitutive gamma2ab/I-Ad presentation was most pronounced in the adherent
      spleen cell fraction and improved by further enrichment for dendritic cells.
      Notably, however, whereas in normal mice the gamma2ab determinant was
      undetectable on B cells lacking surface IgG2ab, such B cells contributed
      considerably to constitutive presentation in (NZB x BXSB)F1 hybrids. Presumably
      this resulted from complement receptor-mediated internalization of IgG2ab
      containing immune complexes formed in lupus. These data add to the evidence that
      B cells with self-reactive receptors, known to exist in the mature repertoire,
      may present non-cognate foreign antigen to anti-foreign helper T lymphocytes and
      thus differentiate into autoantibody-secreting cells, and might likewise account
      for the polyclonal B-cell activation characteristic of several autoimmune
      syndromes.

PMID- 10929073
TI  - Human and rodent decay-accelerating factors (CD55) are not species restricted in
      their complement-inhibiting activities.
AB  - Homologous complement activation is restricted on cells by the complement
      regulators, decay-accelerating factor (DAF), membrane cofactor protein (MCP) and
      CD59. These proteins act in concert with other membrane structures to protect
      cells from homologous complement attack. In contrast, cells are usually sensitive
      to heterologous complement attack. It has been suggested that species-specific
      restriction of complement activation can be attributed to the inability of
      regulators to inhibit across species. We have investigated the capacities of
      human, rat and mouse analogues of DAF to regulate homologous and heterologous
      complement. Cells transfected with cDNA encoding these analogues were protected
      from heterologous complement attack. C3b-deposition experiments indicated that
      whilst cells were best protected by DAF from the same species, all three
      analogues inhibited human, rat and mouse complement. Comparable results were
      obtained in haemolysis assays using soluble, recombinant forms of the proteins.
      Inhibition of the classical pathway (CP) was best achieved with homologous DAF,
      although human DAF also inhibited rat complement, rat DAF also inhibited human
      complement and mouse DAF inhibited complement from all species. Human DAF was the
      best inhibitor of alternative pathway (AP)-mediated attack, inhibiting complement
      from all species. Mouse DAF inhibited mouse and rat AP, whilst rat DAF inhibited
      only rat AP. These data indicate that human and rodent analogues of DAF are not
      species restricted and highlights interesting differences in the capacity to
      regulate AP and CP. This has implications in broader fields of research, such as
      xenotransplantation, where cross-species regulation of complement is of paramount
      importance.

PMID- 10929074
TI  - Naturally occurring polyphenolic antioxidants modulate IgE-mediated mast cell
      activation.
AB  - Reactive oxygen species (ROS) are known to modulate activities of a host of
      kinases, phosphatases and transcription factors. Rutin and chlorogenic acid (CGA)
      are the major polyphenolic antioxidants present in the small molecular fraction
      of smokeless tobacco leaf extracts, as ascertained by reverse-phase high-pressure
      liquid chromatography (HPLC) and mass spectrometry. Levels of intracellular ROS
      in resting versus antigen-immunoglobulin E (IgE)-challenged murine mast cells
      were measured at 510 nm by fluorescence-activated cell sorting (FACS) using
      carboxy-dichlorofluorescein (DCFH-DA). Enhanced ROS production was observed in
      IgE-sensitized mast cells following antigenic challenge. Rutin and CGA reduced
      ROS levels in antigen-IgE-activated mast cells. Concomitantly, they also
      profoundly inhibited histamine release by these activated mast cells. In
      contrast, rutin and CGA augmented the inducible cytokine messages, i.e.
      interleukin (IL)-10, IL-13, interferon-gamma (IFN-gamma), IL-6 and tumour
      necrosis factor-alpha (TNF-alpha) in IgE-sensitized mast cells following antigen
      challenge. This study indicates that tobacco polyphenolic antioxidants that
      quench intracellular ROS, differentially affect two effector functions of antigen
      IgE-activated mast cells. This model system may be employed to determine the
      molecular target of polyphenols. The potential role of these polyphenolic
      antioxidants on IgE-mediated allergy in vivo depends on a balance of their
      differential effects on mast cell activation.

PMID- 10929075
TI  - gammadelta T-cell anergy in human immunodeficiency virus-infected persons with
      opportunistic infections and recovery after highly active antiretroviral therapy.
AB  - gammadelta T lymphocytes recognize non-peptidic microbial antigens without
      antigen processing and major histocompatibility complex (MHC) restriction,
      representing an early defence mechanism against invading pathogens. As a
      defective response to non-peptidic antigens was observed in human
      immunodeficiency virus-positive (HIV+) persons, the aims of this study were
      twofold: to analyse the incidence of gammadelta T-cell anergy in HIV+ positive
      patients with opportunistic infections/co-infections (HIV-OIC), and to
      investigate the role of highly active antiretroviral therapy (HAART) on
      gammadelta T-cell functions. Peripheral gammadelta T-cell distribution and in
      vitro reactivity to a non-peptidic mycobacterial antigen, isopentenyl
      pyrophosphate (IPP), were analysed. gammadelta T-cell subset distribution was
      altered more in HIV-OIC patients than in asymptomatic HIV+ subjects (HIV-ASY).
      Specifically, the Vdelta2/Vdelta1 ratio was inverted as a consequence of a
      decrease in Vdelta2 T-cell number. Moreover, IPP-stimulated Vdelta2 T cells from
      the HIV-OIC group displayed a major defect in interferon-gamma (IFN-gamma)
      production. Interestingly, HAART induced a sustained recovery of naive CD45RA+
      and CD62L+ T cells and restored gammadelta T-cell function. Accordingly, in vitro
      CD45RA depletion resulted in gammadelta T-cell hyporesponsiveness. Altogether,
      the incidence of gammadelta T-cell anergy was increased in HIV-OIC patients and
      dependent on CD45RA helper function. Moreover, HAART was able to restore
      gammadelta T-cell reactivity, extending the immune recovery to non-peptide
      microbial antigens.

PMID- 10929077
TI  - Increased resistance to mycobacterial infection in the absence of interleukin-10.
AB  - Interleukin-10 (IL-10) down-regulates T helper type 1 cell and macrophage
      functions. As IL-10 is induced along with tumour necrosis factor (TNF) and IL-12
      in mycobacterial infection, we asked whether endogenous IL-10 plays a role in the
      antimycobacterial response. We demonstrate here that IL-10-deficient mice
      eliminate Mycobacterium bovis Calmette-Guerin bacillus faster than wild-type
      mice. Granulomas are significantly larger, containing more CD-11b- and CD11c
      positive antigen-presenting cells and T cells, and the expression of major
      histocompatibility complex class II and intracellular adhesion molecule-1 is
      increased. Macrophages in granulomas of IL-10-deficient mice express high levels
      of TNF, acid phosphatase and inducible nitric oxide synthase (iNOS). Finally, an
      increased cutaneous delayed-type hypersensitivity reaction to mycobacterial
      proteins is further evidence of an augmented cell-mediated immune response. In
      conclusion, the cell-mediated immunity is enhanced in the absence of IL-10,
      resulting in a robust granuloma response, which accelerates the clearance of
      mycobacteria. Therefore, endogenous IL-10 attenuates mycobacterial immunity.

PMID- 10929076
TI  - Vitamin E supplementation increases T helper 1 cytokine production in old mice
      infected with influenza virus.
AB  - Compared with young mice, old mice infected with influenza virus have
      significantly higher pulmonary viral titres, although these can be reduced
      significantly with dietary vitamin E supplementation. T helper 1 (Th1) cytokines,
      especially interferon-gamma (IFN-gamma), play an important role in defending
      against influenza infection. However, there is an age-associated loss of Th1
      cytokine production. Prostaglandin E2 (PGE2) production, which increases with
      age, can modulate the T helper cell function by suppressing Th1 cytokine
      production. To investigate the mechanism of vitamin E supplementation on
      reduction of influenza severity in old mice, we studied the cytokine production
      by splenocytes, and PGE2 production by macrophages (Mphi), in young and old C57BL
      mice fed semipurified diets containing 30 (control) or 500 parts per million
      (ppm) (supplemented) vitamin E for 8 weeks, and then infected with influenza
      A/PC/1/73 (H3N2). Old mice fed the control diet had significantly higher viral
      titres than young mice; old mice fed the vitamin E-supplemented diet had
      significantly lower pulmonary viral titres than those fed the control diet (P =
      0.02 and 0.001 for overall age and diet effect, respectively). Following
      influenza infection, interleukin (IL)-2 and IFN-gamma production was
      significantly lower in old mice than in young mice. Vitamin E supplementation
      increased production of IL-2 and IFN-gamma in old mice; higher IFN-gamma
      production was associated with lower pulmonary viral titre. Old mice fed the
      control diet showed significantly higher lipopolysaccharide (LPS)-stimulated Mphi
      PGE2 production than old mice fed the vitamin E diet or young mice fed either
      diet. There was no significant age difference in IL-6, IL-1beta, or tumour
      necrosis factor-alpha (TNF-alpha) production by splenocytes. Young mice fed the
      vitamin E-supplemented diet had significantly lower IL-1beta (day 7) and TNF
      alpha production (day 5) compared with those fed the control diet. Old mice fed
      the vitamin E-supplemented diet had significantly lower TNF-alpha production (day
      2) than those fed the control diet. Our results indicate that the vitamin E
      induced decrease in influenza viral titre is mediated through enhancement of Th1
      cytokines, which may be the result of reduced PGE2 production caused by vitamin
      E.

PMID- 10929078
TI  - Mechanisms of pertussis toxin-induced myelomonocytic cell adhesion: role of CD14
      and urokinase receptor.
AB  - Pertussis toxin (PTX) has been shown previously to promote myelomonocytic cell
      adhesion in serum. The aim of the present study was to identify, using
      transforming growth factor-beta1 and 1, 25-(OH)2 vitamin D3 (TGF-beta1/D3)-primed
      U937 cells, the PTX-binding site(s) and the adhesion molecule(s) responsible for
      PTX-induced myelomonocytic cell adhesion. Monoclonal antibodies (mAbs) directed
      against CD14, CD11b, CD18 or urokinase receptor (uPAR) significantly inhibited
      PTX-induced primed U937 cell adhesion in serum in a concentration-dependent
      manner. However, only anti-CD14 and anti-CD18 mAbs were able to prevent the
      myeloid cells from binding to PTX-coated plates and significantly inhibited a PTX
      induced rise of [Ca2+]i in primed U937 cells. A receptor-isolation study showed
      that biotinylated PTX recognized a 48 000-molecular weight protein in primed U937
      cell lysates, which could be specifically blocked by excess unlabelled PTX or by
      anti-CD14 mAb. On the other hand, mAb directed against uPAR significantly blocked
      PTX-induced myeloid cell adhesion to serum and to immobilized vitronectin, a
      major extracellular matrix protein in serum. Taken together, our data suggest
      that PTX may bind to cell-surface CD14 to induce myelomonocytic cell adhesion to
      vitronectin in serum via uPAR activation, which may represent a pathogenetic
      mechanism for the respiratory tract infection induced by Bordetella pertussis.

PMID- 10929079
TI  - Engineering the microflora to vaccinate the mucosa: serum immunoglobulin G
      responses and activated draining cervical lymph nodes following mucosal
      application of tetanus toxin fragment C-expressing lactobacilli.
AB  - The delivery of antigens to mucosal-associated lymphoid tissues in paediatric and
      immunocompromised populations by safe, non-invasive vectors, such as commensal
      lactobacilli, represents a crucial improvement to prevailing vaccination options.
      In this report, we describe the oral and nasal immunization of mice with vaccines
      constructed through an original system for heterologous gene expression in
      Lactobacillus in which the 50 000-molecular weight (MW) fragment C of tetanus
      toxin (TTFC) is expressed either as an intracellular or a surface-exposed
      protein. Our data indicate that L. plantarum is more effective in this respect
      than L. casei and that, under the experimental conditions investigated, delivery
      of TTFC expressed as an intracellular antigen is more effective than cell-surface
      expression. Immunization of mice with live recombinant lactobacilli induced
      significant levels of circulating TTFC-specific immunoglobulin G (IgG) following
      nasal or oral delivery of vaccine strains. In addition, following nasal delivery,
      secretory immunoglobulin A (sIgA) was induced in bronchoalveolar lavage fluids,
      as were antigen-specific antibody-secreting cells and antigen-specific T-cell
      activation in draining lymph nodes, substantiating their potential for safe
      mucosal delivery of paediatric vaccines.

PMID- 10929080
TI  - Glucocorticoids, ageing and nerve cell damage.

PMID- 10929081
TI  - In vivo modulation of post-spike excitability in vasopressin cells by kappa
      opioid receptor activation.
AB  - An endogenous kappa-opioid agonist reduces the duration of phasic bursts in
      vasopressin cells. Non-synaptic post-spike depolarizing after-potentials underlie
      activity during bursts by increasing post-spike excitability and kappa-receptor
      activation reduces depolarizing after-potential amplitude in vitro. To
      investigate the effects of kappa-opioids on post-spike excitability in vivo, we
      analysed extracellular recordings of the spontaneous activity of identified
      supraoptic nucleus vasopressin cells in urethane-anaesthetized rats infused with
      Ringer's solution (n = 17) or the kappa-agonist, U50,488H (2.5 microg/h at 0.5
      microl/h; n = 23), into the supraoptic nucleus over 5 days. We plotted the mean
      hazard function for the interspike interval distributions as a measure of the
      post-spike excitability of these cells. Following each spike, the probability of
      another spike firing in vasopressin cells recorded from U50,488H infused nuclei
      was markedly reduced compared to Ringer's treated vasopressin cells. To determine
      whether U50,488H could reduce post-spike excitability in cells that displayed
      spontaneous phasic activity, we infused U50,488H (50 microg/h at 1 microl/h,
      i.c.v.), for 1-12 h while recording vasopressin cell activity. Nine of 10
      vasopressin cells were silenced by i.c.v. U50,488H 15 +/- 5 min into the
      infusion. Six cells exhibited spontaneous phasic activity before U50,488H
      infusion and recordings from three of these phasic cells were maintained until
      activity recovered; during U50,488H infusion, the activity of these three cells
      was irregular. Generation of the mean hazard function before and during U50,488H
      infusion revealed a reduction in post-spike excitability during U50,488H
      infusion. Thus, kappa-receptor activation reduces post-spike excitability in
      vivo; this may reflect inhibition of depolarizing after-potentials and may thus
      underlie the reduction in burst duration of vasopressin cells caused by an
      endogenous kappa-agonist in vivo.

PMID- 10929083
TI  - Early environmental regulation of glucocorticoid feedback sensitivity in young
      adult monkeys.
AB  - Variations in maternal care induce in neonatal rodents life-long changes in
      glucocorticoid feedback regulation of the hypothalamic-pituitary-adrenal axis.
      This aspect of plasticity in neuroendocrine development has not been established
      in primates. We assessed, in young adult squirrel monkeys, postnatal rearing
      effects on cortisol-induced suppression of corticotropin-releasing factor (CRF)
      stimulated secretion of adrenocorticotropic hormone (ACTH). Offspring of randomly
      bred monkeys were periodically removed from natal groups between 13 and 21 weeks
      of age. In two other postnatal rearing conditions, systematic differences in
      maternal availability were produced by manipulating the effort required of
      lactating mothers to successfully find food. All offspring were subsequently
      administered, 3-5 years later on two occasions, an intravenous ovine CRF
      injection preceded 60 min earlier by placebo or cortisol pretreatment. The
      difference between CRF-stimulated time-integrated secretion of ACTH following
      placebo vs cortisol pretreatment served as an index of glucocorticoid negative
      feedback. Difference scores were greatest in monkeys previously separated from
      natal groups. This finding was not attributable to significant rearing condition
      differences in plasma cortisol levels achieved following pretreatment with
      exogenous cortisol, nor plasma ACTH levels produced when the CRF injection was
      preceded by pretreatment with placebo. The results suggest that postnatal
      experiences altered glucocorticoid feedback in monkeys at least through early
      adulthood. This conclusion supports retrospective reports indicating that, for
      humans with major mood and anxiety disorders, systematic differences in
      glucocorticoid feedback may reflect neural mechanisms in development linking
      early life stress with psychopathology in adulthood.

PMID- 10929082
TI  - Adrenalectomy dramatically modifies the dynamics of neuropeptide and c-fos gene
      responses to stress in the hypothalamic paraventricular nucleus.
AB  - We have used in situ hybridization and radio-immunoassay to compare temporal
      dynamics of components in the hypothalamo-pituitary limb of the hypothalamo
      pituitary-adrenal axis during sustained hypovolemic stress in adrenalectomized
      (ADX) rats to those previously reported in intact animals. We asked three
      questions: first, does corticotropin-releasing hormone (CRH) gene transcription
      occur in neuroendocrine neurones of the hypothalamic paraventricular nucleus
      (PVH) of ADX rats, and if so, how is it temporally organized; second, what is the
      expression pattern of the vasopressin and other genes known to be colocalized in
      these neuroendocrine neurones; third, if adrenocorticotropin hormone (ACTH)
      secretion occurs, what is its temporal profile? We found that sustained
      hypovolemia evoked a brief episode of CRH gene transcription in ADX rats that
      occurred earlier than in intact rats. However, in contrast to saline-injected
      controls, this activation was not maintained because declines in CRH hnRNA and
      mRNA were seen as the stress continued. Although increased vasopressin gene
      transcription was not seen in intact hypovolemic rats, robust increases were
      measured throughout in ADX rats, suggesting that in the absence of corticosterone
      the vasopressin gene is transcribed preferentially to the CRH gene during
      sustained hypovolemia. c-fos and preproenkephalin mRNA profiles also exhibited
      earlier onsets compared to intact rats. Finally, the onset and duration of ACTH
      secretion was the same in ADX rats as previously reported in intact rats.
      Collectively, these data support two hypotheses regarding the actions of
      corticosterone. First, that it provides some form of facilitatory signal allowing
      neuroendocrine CRH transcriptional mechanisms to remain active during sustained
      hypovolemia. Second, that it strongly inhibits the response of the vasopressin
      gene to hypovolemic stress.

PMID- 10929084
TI  - Synchronized clusters of action potentials can increase or decrease the
      excitability of the axons of magnocellular hypothalamic neurosecretory cells.
AB  - Extracellular recordings were made from supraoptic nucleus (SON) cells in
      urethane anaesthetized male rats in vivo. Two stimulating electrodes were
      positioned to activate the cells antidromically, one in the mid axon region of
      the cells and the other at the axon terminals. Trains of 5-20 just-subthreshold
      stimuli at 5 s intervals decreased the threshold for antidromic activation from
      both sites. Whereas neither single stimuli, nor the stimuli at the beginning of a
      train of 20 stimuli evoked antidromic action potentials, later action potentials
      did so. Paradoxically, trains of 20 just-suprathreshold stimuli increased the
      threshold for activation of both axons and terminals. In recordings from the same
      cells, stimuli were applied singly at 5 s intervals at an intensity which almost
      invariably evoked an antidromic action potential. Identical stimuli were then
      applied in trains of 20 stimuli at 50 Hz. After the first train, the initial
      stimulus pulses of the trains frequently fell below threshold. Following a
      conditioning train of five stimuli applied to one electrode, the period of
      decreased threshold (increased excitability) at the other electrode lasted less
      than 100 ms and the period of increased threshold (decreased excitability) after
      12 trains of 20 stimuli lasted between 5 and 10 s. Both decreased and increased
      excitability were seen at axons and terminals of both putative oxytocin and
      vasopressin cells. Since the excitability changes were shown in vivo at
      frequencies encountered during recordings, it is likely that they influence the
      probability of spike propagation and hormone secretion under physiological
      conditions.

PMID- 10929085
TI  - Regulation of central corticosteroid receptors following short-term activation of
      serotonin transmission by 5-hydroxy-L-tryptophan or fluoxetine.
AB  - Alterations of the hypothalamic-pituitary-adrenal (HPA) axis function
      characterized by a decreased negative feedback capacity are often associated with
      affective disorders and are corrected by treatment with antidepressant drugs. To
      gain a better understanding of the effects of the antidepressant drug fluoxetine,
      a specific serotonin (5-HT) reuptake inhibitor, on central corticosteroid
      receptors, the effects of short-term activation of serotonin transmission on
      central corticosteroid receptor expression were analysed in adrenalectomized
      (ADX) rats either supplemented or not with corticosterone. Serotonin transmission
      was stimulated either by a single injection of the 5-HT precursor, 5-hydroxy-L
      tryptophan (5-HTP), or by a 2-day treatment with fluoxetine. In ADX rats,
      administration of 5-HTP decreased hippocampal mineralocorticoid (MR) and
      glucocorticoid (GR) receptor numbers 24 h later, while their respective mRNAs
      were unchanged and these effects of 5-HTP were mediated by 5-HT2 receptors. In
      the hypothalamus, GR mRNAs and binding sites decreased 3 h and 24 h after 5-HTP,
      respectively. By contrast, fluoxetine treatment increased hippocampal MR and GR
      mRNAs and MR binding sites while GR number remained unchanged. In ADX rats
      supplemented with corticosterone, 5-HTP and fluoxetine treatment had the same
      effects on corticosteroid receptors compared to those observed in non
      supplemented ADX rats: 5-HTP decreased hippocampal MR and GR and hypothalamic GR
      while fluoxetine treatment increased hippocampal MR. These results show that
      short-term stimulation of 5-HT transmission by 5-HTP decreases hippocampal and
      hypothalamic corticosteroid receptor numbers through a corticosterone-independent
      mechanism. It is hypothesized that the delayed maximal increase in extracellular
      5-HT contents after fluoxetine treatment, due to negative feedback regulations
      induced by the activation of 5-HT1A and 5-HT1B autoreceptors, is not the primary
      cause for the delayed normalization of corticosteroid receptor numbers that
      regulates the HPA axis functioning.

PMID- 10929086
TI  - Photoperiod-dependent and -independent regulation of melatonin receptors in the
      forebrain of songbirds.
AB  - Melatonin was recently identified as playing a role in fine-tuning the effects of
      gonadal steroids in the regulation of seasonal neuroplasticity within the
      telencephalic song control system of European starlings. The present study
      investigated possible seasonal regulation of melatonin receptors (MelR) within
      the starling song control system, in the presence or absence of gonadal steroids.
      Brains were sampled from photosensitive starlings exposed to short days,
      photostimulated starlings exposed to long days and photorefractory starlings also
      exposed to long days. Each condition contained a group of gonad-intact birds and
      a group of castrated birds. Melatonin receptor distribution was assessed in vitro
      by 125-iodomelatonin (IMEL) receptor autoradiography. In general, MelR
      distribution was similar to that described in other songbird species. However,
      there was a striking downregulation of MelR in the song control nucleus Area X of
      intact and castrated photostimulated birds on long days compared to their
      photorefractory counterparts on the same long days and to the short-day groups.
      Downregulation of MelR occurred independently of gonadal steroids. Nevertheless,
      superimposed on this general pattern of MelR downregulation during
      photostimulation, IMEL binding was observed in a medial subdivision of Area X
      when gonadal steroids were present. Downregulation of MelR in Area X during the
      short breeding season has implications for seasonal regulation of the song
      control system. Subsequent upregulation of MelR as birds become photorefractory,
      in the absence of any change in photoperiod, gonadal steroids or melatonin signal
      is the first description of photoperiod-independent regulation of MelR in adults
      of any vertebrate class.

PMID- 10929087
TI  - Suppression of adrenocorticotropic hormone release by stimulation of the nerve
      fibres in the anterior pituitary.
AB  - With the recent revelation of considerable peptidergic innervation of the
      anterior pituitary in several mammalian species, including man, it becomes
      imperative to elucidate the physiological significance of such a morphological
      entity. We addressed this issue by employing an anterior pituitary slice in vitro
      superfusion system coupled with electrical field stimulation. Anterior pituitary
      slices of 0.8 mm were perfused with Krebs-Ringer bicarbonate-bovine serum albumin
      buffer in a superfusion chamber for 30 min before electrical field stimulation. A
      square current of 30 mA, 10 Hz and 0.5 ms was then applied for 10 min. The
      perfusate was collected every 10 min and measured for adrenocorticotropic hormone
      (ACTH) by radio-immunoassay. It was found that under the experimental condition
      the basal release of ACTH was suppressed by electrical field stimulation of the
      nerve fibres in the anterior pituitary. Furthermore, vasopressin was added as a
      secretagogue. The suppression of ACTH by electrical field stimulation became even
      more marked. This is the first physiological evidence of the effect of
      stimulation of the nerve fibres innervating the anterior pituitary on its
      secretory activity.

PMID- 10929088
TI  - Effect of melatonin treatment on 24-h variations in responses to mitogens and
      lymphocyte subset populations in rat submaxillary lymph nodes.
AB  - Wistar male rats were injected s.c. with melatonin (30 microg) or vehicle, 1 h
      before lights off, for 11 days. Ten days after beginning melatonin treatment,
      rats received Freund's complete adjuvant or its vehicle s.c., and after 2 days,
      they were sacrificed at six different time intervals throughout a 24-h cycle. The
      mitogenic effect of lipopolysaccharide (LPS) and concanavalin A (Con A), the
      activity of ornithine decarboxylase (ODC) and the relative size of lymphocyte
      subset populations were measured in submaxillary lymph nodes. In control rats,
      the mitogenic effects of LPS and Con A and ODC activity peaked during the
      afternoon. Injection of Freund's adjuvant induced a 10-h shift in the diurnal
      rhythm of the mitogenic effect of LPS to attain maximal values at night.
      Melatonin pretreatment blunted the daily variations in the mitogenic activity of
      Con A or LPS and, when given to Freund's adjuvant-injected rats, augmented mesor
      and amplitude of diurnal rhythm in ODC activity. Maxima in B cell number occurred
      at night whereas those of T and B-T cell number occurred during the afternoon.
      During the early phase of immunization tested, the number of B cells augmented
      and the amplitude of its diurnal rhythmicity increased both after immunization
      and following melatonin pretreatment. Maxima of 24-h rhythms in CD4+ and
      CD4+/CD8+ cell populations occurred during the afternoon while those of CD8+
      cells occurred at late night. Melatonin significantly augmented CD4+ cell number
      and decreased CD8+ cell number; it therefore augmented the CD4+:CD8+ ratio. The
      results suggest that pretreatment with a pharmacological dose of melatonin exerts
      immunomodulating effects at an early, preclinical, phase of Freund's adjuvant
      induced arthritis in rats.

PMID- 10929089
TI  - Effects of the inhibition of cyclo-oxygenase 1 or 2 or 5-lipoxygenase on the
      activation of the hypothalamic-pituitary-adrenal axis induced by interleukin
      1beta in the male Rat.
AB  - The limited entry of interleukin-1beta (IL-1beta) into the central nervous system
      has led to the hypothesis that IL-1beta acts, through IL-1beta receptors located
      notably on endothelial cells, on the release of prostaglandins which in turn
      stimulate the hypothalamic-pituitary-adrenal (HPA) axis. We used cyclo-oxygenase
      1 (COX-1) and cyclo-oxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors,
      before the injection of IL-1beta, to explore the role of arachidonic acid
      metabolic pathways on HPA axis activation. Adult male rats were i.m injected 20
      min before i.p injection of IL-1beta, with (i): a COX-1/COX-2 inhibitor
      (ketoprofen); (ii) a COX-2 selective inhibitor (NS 398); or (iii) a 5-LOX
      inhibitor (BW A4C). Following this, rats were killed 90 min after i.p. IL-1beta
      injection and analysis for plasma adrenocorticotropic hormone (ACTH) and
      corticosterone concentrations and determination of anterior pituitary pro-opio
      melanocortin (POMC) gene transcription was conducted. Administration of the COX
      1/COX-2 inhibitor led to a complete blockage of ACTH and corticosterone secretion
      and POMC gene transcription. The COX-2 inhibitor led to a complete blockade of
      ACTH secretion and POMC gene transcription but had no effect on corticosterone
      secretion. The 5-LOX inhibitor had no significant effect on any parameter. These
      results demonstrate the crucial role of eicosanoid pathways in mediating the
      stimulation of the HPA axis induced by IL-1beta. Moreover, we found a clear
      dissociation of the effect of the blockage of COXs upon ACTH and corticosterone
      secretion, suggesting that IL-1beta may act at the brain as well as at the
      adrenal cortex to stimulate the secretion of corticosterone.

PMID- 10929090
TI  - Thyroxine modulates corticotropin-releasing factor but not arginine vasopressin
      gene expression in the hypothalamic paraventricular nucleus of the developing
      Rat.
AB  - Neonatal rats were daily injected with 100 microg/kg T4 and killed at 4, 8 or 15
      days. Circulating corticosterone and corticosteroid binding globulin
      concentrations increased in 8- and 15-day-old rats after T4 treatment. Plasma
      adrenocorticotropic hormone (ACTH) concentrations, pituitary ACTH content and pro
      opiomelanocortin mRNA expression were unaffected in T4-treated rats. T4 treatment
      induced an increase in corticotropin-releasing factor (CRF) mRNA expression in
      the whole population of CRF synthesizing cells of the paraventricular nucleus
      (PVN) that became significant at day 8 and disappeared at day 15. Double
      labelling in situ hybridization revealed that CRF gene expression in the
      CRF+/arginine vasopressin (AVP)+ subpopulation was increased at days 4 and 8 and
      decreased at day 15. CRF immunoreactivity in the zona externa of the median
      eminence increased with age but was not affected by the experimental
      hyperthyroidism. The degree of CRF and AVP colocalization, the concentration of
      AVP mRNA in the parvo and magnocellular cell bodies of the PVN and the density of
      immunoreactive AVP in the zona interna or zona externa of the median eminence did
      not change after T4 treatment. Our data demonstrate that experimental
      hyperthyroidism accelerates the maturation of hypothalamic CRF gene expression,
      including in particular in the CRF+/AVP+ subpopulation, during the stress
      hyporesponsive period. These observations suggest that the physiological peak of
      plasma thyroxine that occurs between days 8-12 may participate in the maturation
      of hypothalamic CRF cells.

PMID- 10929091
TI  - Effects of chronic oestrogen replacement on stress-induced activation of
      hypothalamic-pituitary-adrenal axis control pathways.
AB  - Oestrogen replacement therapy reportedly suppresses hypothalamic-pituitary
      adrenal (HPA) axis responses to an emotional stressor in postmenopausal women.
      However, most studies in the rat suggest a facilitatory role for oestrogen in the
      control of HPA axis function. One explanation for this difference may be the
      regimen of oestrogen replacement: during oestrogen replacement therapy, oestrogen
      levels are low and constant whereas most animal studies examined the HPA axis
      response when oestrogen levels are rising. In the present study, we assessed HPA
      axis stress responses in mature ovariectomized rats after plasma oestrogen levels
      had been maintained at physiological levels for a prolonged period (25 or 100
      pg/ml for 7 days). In the case of both an emotional stressor (noise) and a
      physical stressor (immune challenge by systemic interleukin-1beta
      administration), oestrogen replacement suppressed stress-related Fos-like
      immunolabelling, in hypothalamic neuroendocrine cells and plasma
      adrenocorticotropin hormone responses. From the present data, and past reports,
      it appears unlikely that these effects of oestrogen are due to a direct action on
      corticotropin-releasing factor or oxytocin cells. Therefore, to obtain some
      indication of oestrogen's possible site(s) of action, Fos-like immunolabelling
      was mapped in the amygdala and in brainstem catecholamine groups, which are
      neuronal populations demonstrating substantial evidence of involvement in the
      generation of HPA axis stress responses. In the amygdala, oestrogen replacement
      suppressed central nucleus responses to immune challenge, but not to noise.
      Amongst catecholamine cells, oestrogen replacement was more effective against
      responses to noise than immune challenge, suppressing A1 and A2 (noradrenergic)
      and C2 (adrenergic) responses to noise, but only A1 responses to immune
      challenge. These data suggest that, as in postmenopausal women on oestrogen
      replacement therapy, chronic low-level oestrogen replacement can suppress HPA
      axis stress responses in the rat. Moreover, oestrogen appears to exert effects at
      multiple sites within putative HPA axis control pathways, even though most of the
      relevant neuronal populations do not contain genomic receptors for this gonadal
      steroid and the pattern of oestrogen action differs for an emotional vs a
      physical stressor.

PMID- 10929092
TI  - The effects of acute and chronic stresses on vasotocin gene transcripts in the
      brain of the rainbow trout (Oncorhynchus mykiss).
AB  - Secretion of adrenocorticotropic hormone (ACTH) from the fish pituitary, which
      occurs in times of stress, is stimulated by several hypothalamic neuropeptides,
      one of which is arginine vasotocin (AVT). This study investigates whether gene
      expression for AVT is up-regulated during acute or chronic stress. Rainbow trout
      (Oncorhynchus mykiss) were subjected to one of two forms of acute stress-either 2
      h confinement followed by 2 h recovery, or capture and transfer to low water for
      2 min followed by 4 h recovery in their home tank before autopsy. In other
      experiments, these stresses were repeated daily for 5 or 6 days (chronic stress).
      Quantification of AVT transcript prevalence in the parvocellular and
      magnocellular neurones of the preoptic nucleus after in situ hybridization was
      used as a monitor of the AVT gene response to stress. The results showed that
      acute confinement, but apparently not brief low-water stress, significantly
      increased AVT transcript prevalence in a group of parvocellular perikarya. When
      applied repeatedly, both forms of stress caused habituation, such that the AVT
      hybridization signal remained at control or even lower levels despite elevated
      pro-opiomelanocortin transcripts in the corticotropes and raised plasma cortisol
      concentrations. The AVT hybridization signal in the magnocellular perikarya
      showed no significant response to either acute or chronic stress. The results
      support the idea that these parvocellular AVT neurones are involved in ACTH
      stimulation during acute stress, and that the system habituates to chronic
      stresses.

PMID- 10929093
TI  - Area postrema ablation attenuates activation of neurones in the paraventricular
      nucleus in response to systemic adrenomedullin.
AB  - Adrenomedullin (ADM) is a potent vasodilator in the periphery which also acts
      centrally to increase blood pressure and inhibit drinking, feeding and salt
      appetite. This study was designed to study the effects of circulating ADM on
      neuronal activation in autonomic centres in the rat brain and to examine whether
      neuronal nitric oxide (NO) may participate in these processes. We identified
      activated neurones 1 h after intravenous (i.v.) injections of ADM (2 nmol/kg)
      using immunohistochemistry for Fos. The nicotinamide adenine dinucleotide
      phosphate-diaphorase (NADPH-d) histochemical reaction was used to localize
      putative NO-producing neurones and double labelling for Fos and NADPH-d was used
      to identify activated NO producing neurones. To separate baroreceptor-induced
      neuronal activation in autonomic centres by ADM from other effects which it may
      have, i.v. infusions of sodium nitroprusside (NP) were used to mimic the
      hypotensive effects of ADM in control rats. Significantly greater numbers of
      activated neurones were found in the paraventricular nucleus of the hypothalamus
      (PVN) and especially in the dorsolateral medial parvocellular division, the
      nucleus of the solitary tract, and the area postrema (AP) of ADM-treated rats
      compared to control rats. In addition, the number of activated NO-producing
      neurones in the PVN was significantly higher in ADM-treated rats compared to rats
      treated with NP. To determine whether AP is one of the possible routes through
      which systemic ADM enters the brain to exert its central effects, the APs of rats
      were ablated by aspiration. One hour after i.v. injections of ADM, significantly
      fewer PVN neurones were activated in AP ablation rats compared to AP sham
      ablation rats. Similarly, the number of activated NO-producing neurones in the
      PVN was significantly lower in AP ablation rats compared to AP sham ablation
      rats. In conclusion, our results suggest that systemic ADM gains access to the
      brain through the AP to regulate neuronal activity in autonomic centres and that
      neuronal NO might be involved in central autonomic and/or neuroendocrine
      regulation by ADM.

PMID- 10929095
TI  - The early years

PMID- 10929094
TI  - Attenuation of hypothalamic-pituitary-adrenal axis stress responses in late
      pregnancy: changes in feedforward and feedback mechanisms.
AB  - The hypothalamic-pituitary-adrenal axis is hyporesponsive to stress in late
      pregnancy, exemplified as reduced adrenocorticotropic hormone (ACTH) and
      corticosterone responses to restraint, but the mechanisms are unknown. We
      investigated forward drive and negative feedback upon the hypothalamic-pituitary
      adrenal axis in pregnant rats. Corticotropin-releasing hormone (CRH) and
      vasopressin mRNA expression in the parvocellular paraventricular nucleus and
      mineralocorticoid and glucocorticoid receptor expression in the paraventricular
      nucleus and hippocampus were quantified with in situ hybridization. Because it
      can enhance the corticosterone negative feedback signal, 11beta-hydroxysteroid
      dehydrogenase type 1 (11beta-HSD1) bioactivity in these brain regions and
      anterior pituitary was measured in vitro, and ACTH and corticosterone stress
      responses were measured after intracerebroventricular glycyrrhetinic acid, an
      11beta-HSD inhibitor. Changes in corticosterone feedback on ACTH secretion were
      examined after pharmacological adrenalectomy by metyrapone and aminoglutethimide.
      Parvocellular paraventricular nucleus CRH mRNA content was reduced on day 21 and
      the CRH mRNA : vasopressin mRNA ratio was unaltered, indicating decreased
      production of both CRH and vasopressin. An increase in glucocorticoid receptor
      mRNA expression in the dentate gyrus (mineralocorticoid receptor mRNA expression
      was unaltered) and increased 11beta-HSD1 activity in the paraventricular nucleus
      and anterior pituitary suggest an increase in slow negative feedback mechanisms
      in pregnancy, but glycyrrhetinic acid did not modify the stress response. After
      metyrapone/aminoglutethimide treatment, corticosterone decreased ACTH secretion
      more slowly in pregnancy, indicating a decrease in rapid feedback sensitivity.
      Thus, reduced forward drive rather than increased effectiveness of glucocorticoid
      negative feedback may underlie stress hyporesponsiveness of the hypothalamic
      pituitary-adrenal axis in pregnancy.

PMID- 10929097
TI  - Jeff schell in cologne

PMID- 10929096
TI  - Ten years dedicated to the laboratory of genetics, gent

PMID- 10929098
TI  - The transfer of DNA from agrobacterium tumefaciens into plants: a feast of
      fundamental insights.

PMID- 10929099
TI  - rgf1, a mutation reducing grain filling in maize through effects on basal
      endosperm and pedicel development.
AB  - The maize cob presents an excellent opportunity to screen visually for mutations
      affecting assimilate partitioning in the developing kernel. We have identified a
      defective kernel mutant termed rgf1, reduced grain filling, with a final grain
      weight 30% of the wild type. In contrast with most defective endosperm mutants,
      rgf1 shows gene dosage-dependent expression in the endosperm. rgf1 kernels
      possess a small endosperm incompletely filling the papery pericarp, but embryo
      development is unaffected and the seeds are viable. The mutation conditions
      defective pedicel development and greatly reduces expression of endosperm
      transfer layer-specific markers. rgf1 exhibits striking morphological
      similarities to the mn1 mutant, but maps to a locus approximately 4 cM away from
      mn1 on chromosome 2 of maize. Despite reduced starch accumulation in the mutant,
      no obvious lesion in starch biosynthesis has been detected. Free sugar levels are
      unaltered in rgf1 endosperm. Rates of sugar uptake, measured over short (8 h)
      periods in cultured kernels, are increased in rgf1 compared to the wild type.
      rgf1 and wild-type kernels, excised at 5 DAP and cultured in vitro also develop
      differently in response to variations in sugar regime: glucose concentrations
      above 1% arrest placentochalazal development of rgf1 kernels, but have no effect
      on cultured wild-type kernels. These findings suggest that either uptake or
      perception of sugar(s) in endosperm cells at 5-10 DAP determines the rgf1 kernel
      phenotype.

PMID- 10929100
TI  - Antisense inhibition of plastidial phosphoglucomutase provides compelling
      evidence that potato tuber amyloplasts import carbon from the cytosol in the form
      of glucose-6-phosphate.
AB  - The aim of this work was to establish whether plastidial phosphoglucomutase is
      involved in the starch biosynthetic pathway of potato tubers and thereby to
      determine the form in which carbon is imported into the potato amyloplast. For
      this purpose, we cloned the plastidial isoform of potato PGM (StpPGM), and using
      an antisense approach generated transgenic potato plants that exhibited decreased
      expression of the StpPGM gene and contained significantly reduced total
      phosphoglucomutase activity. We confirmed that this loss in activity was due
      specifically to a reduction in plastidial PGM activity. Potato lines with
      decreased activities of plastidial PGM exhibited no major changes in either whole
      plant or tuber morphology. However, tubers from these lines exhibited a dramatic
      (up to 40%) decrease in the accumulation of starch, and significant increases in
      the levels of sucrose and hexose phosphates. As tubers from these lines exhibited
      no changes in the maximal catalytic activities of other key enzymes of
      carbohydrate metabolism, we conclude that plastidial PGM forms part of the starch
      biosynthetic pathway of the potato tuber, and that glucose-6-phosphate is the
      major precursor taken up by amyloplasts in order to support starch synthesis.

PMID- 10929101
TI  - Comparative genome analysis reveals extensive conservation of genome organisation
      for Arabidopsis thaliana and Capsella rubella.
AB  - Genome colinearity has been studied for two closely related diploid species of
      the Brassicaceae family, Arabidopsis thaliana and Capsella rubella. Markers
      mapping to chromosome 4 of A. thaliana were found on two linkage groups in
      Capsella and colinear segments spanning more than 10 cM were revealed. Detailed
      analysis of a 60 kbp region in A. thaliana and its counterpart in C. rubella
      showed virtually complete conservation of gene repertoire, order and orientation.
      The comparison of orthologous genes revealed very similar exon-intron structures
      and sequence identities of 90% or more were found for exon sequences. This
      extensive genome colinearity at the genetic and molecular level allows the
      efficient transfer of data from the well-studied A. thaliana genome to other
      species in the Brassicaceae family, substantially facilitating genome analysis
      studies for species of this family.

PMID- 10929102
TI  - Developmentally and transgene regulated nuclear processing of primary transcripts
      of chalcone synthase A in petunia.
AB  - The introduction of chalcone synthase A transgenes into petunia plants can result
      in degradation of chalcone synthase A RNAs and loss of chalcone synthase, a
      process called cosuppression or post-transcriptional gene silencing. Here we show
      that the RNA degradation is associated with changes in premRNA processing, i.e.
      loss of tissue specificity in transcript cleavage patterns, accumulation of
      unspliced molecules, and use of template-specific secondary poly(A) sites. These
      changes can also be observed at a lower level in leaves but not flowers of
      nontransgenic petunias. Based on this, a model is presented of how transgenes may
      disturb the carefully evolved, developmentally controlled post-transcriptional
      regulation of chalcone synthase gene expression by influencing the survival rate
      of the endogenous and their own mRNA.

PMID- 10929103
TI  - Cell cycle function of a Medicago sativa A2-type cyclin interacting with a
      PSTAIRE-type cyclin-dependent kinase and a retinoblastoma protein.
AB  - In plants multiple A-type cyclins with distinct expression patterns have been
      isolated and classified into three subgroups (A1-A3), while in animal somatic
      cells a single type of cyclin A is required for cell-cycle regulation from the S
      to M phases. We studied the function of an A2-type cyclin from Medicago sativa
      (Medsa;cycA2) which, in contrast to animal and most plant A-type cyclins, was
      expressed in all phases of the cell cycle. Using synchronized alfalfa cell
      cultures and anti-Medsa;CycA2 polyclonal antibodies, we showed that while the
      mRNA level increased steadily from the late G1 to the G2-M phase, the protein
      level after a rapid increase in S-phase reached a plateau during the G2 phase. In
      the yeast two-hybrid system, the Medsa;CycA2 protein interacted with the PSTAIRE
      motif-containing cyclin-dependent kinase Cdc2MsA and with the maize
      retinoblastoma protein. Unexpectedly, the CycA2-associated kinase activity was
      biphasic: a first activity peak occurred in the S phase while the major one
      occurred during the G2/M transition, with no apparent dependence upon the actual
      levels of the Medsa;CycA2 and Cdc2MsA proteins. Immunohistological localization
      of the cyclin A2 protein by immunofluorescence and immunogold labelling revealed
      the presence of Medsa;CycA2 in the nucleus of the interphase and prophase cells,
      while it was undetectable thereafter during mitosis. Together these data suggest
      that Medsa;CycA2 plays a role both in the S phase and at the G2/M transition.

PMID- 10929104
TI  - Inhibition of serine/threonine-specific protein phosphatases causes premature
      activation of cdc2MsF kinase at G2/M transition and early mitotic microtubule
      organisation in alfalfa.
AB  - Reversible phosphorylation of serine/threonine residues of cell cycle-regulatory
      proteins is one of the key molecular mechanisms controlling eukaryotic cell
      division. In plants, the protein kinase partners (i.e. p34cdc2/CDC28-related
      kinases) have been extensively studied, while the role of counter-acting protein
      phosphatases is less well understood. We used endothall (ET) as a cell-permeable
      inhibitor of serine/threonine-specific protein phosphatases to alter cytological
      and biochemical characteristics of cell division in cultured alfalfa cells. A
      high concentration of ET (10 and 50 microM) inhibited both protein phosphatases 1
      and 2 (PP1 and PP2A), while a low concentration (1 microM) of ET-treatment
      primarily reduced the PP2A activity. High concentrations of the inhibitor
      increased the frequency of hypercondensed early and late prophase chromosomes
      that could not enter metaphase. In contrast, a low concentration of ET did not
      interfere with chromosomal events but caused significant alterations in the
      organisation of microtubules. Exposure of cells to 1 microM ET resulted in
      disturbance of preprophase band formation, increase in the number of nuclei with
      prophase microtubule assembly, premature polarisation of the spindle, and
      abnormal phragmoplast maturation. Under the same conditions, the ET-treated cells
      exhibited an early increase in cdc2MsF kinase activity. These results suggest
      that PP2A contributes to the control of mitotic kinase activities and microtubule
      organisation. Normal chromosome condensation and mitotic progression are
      dependent on both PP1 and PP2A activities. The presented data support the
      functional role of protein phosphatases in the co-ordination of chromosomal and
      microtubule events in dividing plant cells.

PMID- 10929105
TI  - Short root mutant of Lotus japonicus with a dramatically altered symbiotic
      phenotype.
AB  - Legume plants carefully control the extent of nodulation in response to rhizobial
      infection. To examine the mechanism underlying this process we conducted a
      detailed analysis of the Lotus japonicus hypernodulating mutants, har1-1, 2 and 3
      that define a new locus, HYPERNODULATION ABERRANT ROOT FORMATION (Har1), involved
      in root and symbiotic development. Mutations in the Har1 locus alter root
      architecture by inhibiting root elongation, diminishing root diameter and
      stimulating lateral root initiation. At the cellular level these developmental
      alterations are associated with changes in the position and duration of root cell
      growth and result in a premature differentiation of har1-1 mutant root. No
      significant differences between har1-1 mutant and wild-type plants were detected
      with respect to root growth responses to 1-aminocyclopropane1-carboxylic acid,
      the immediate precursor of ethylene, and auxin; however, cytokinin in the
      presence of AVG (aminoetoxyvinylglycine) was found to stimulate root elongation
      of the har1-1 mutant but not the wild-type. After inoculation with Mesorhizobium
      loti, the har1 mutant lines display an unusual hypernodulation (HNR) response,
      characterized by unrestricted nodulation (hypernodulation), and a concomitant
      drastic inhibition of root and shoot growth. These observations implicate a role
      for the Har1 locus in both symbiotic and non-symbiotic development of L.
      japonicus, and suggest that regulatory processes controlling nodule organogenesis
      and nodule number are integrated in an overall mechanism governing root growth
      and development.

PMID- 10929106
TI  - Functional identification of an Arabidopsis snf4 ortholog by screening for
      heterologous multicopy suppressors of snf4 deficiency in yeast.
AB  - Yeast Snf4 is a prototype of activating gamma-subunits of conserved Snf1/AMPK
      related protein kinases (SnRKs) controlling glucose and stress signaling in
      eukaryotes. The catalytic subunits of Arabidopsis SnRKs, AKIN10 and AKIN11,
      interact with Snf4 and suppress the snf1 and snf4 mutations in yeast. By
      expression of an Arabidopsis cDNA library in yeast, heterologous multicopy snf4
      suppressors were isolated. In addition to AKIN10 and AKIN11, the deficiency of
      yeast snf4 mutant to grown on non-fermentable carbon source was suppressed by
      Arabidopsis Myb30, CAAT-binding factor Hap3b, casein kinase I, zinc-finger
      factors AZF2 and ZAT10, as well as orthologs of hexose/UDP-hexose transporters,
      calmodulin, SMC1-cohesin and Snf4. Here we describe the characterization of
      AtSNF4, a functional Arabidopsis Snf4 ortholog, that interacts with yeast Snf1
      and specifically binds to the C-terminal regulatory domain of Arabidopsis SnRKs
      AKIN10 and AKIN11.

PMID- 10929107
TI  - Cell division events are essential for embryo patterning and morphogenesis:
      studies on dominant-negative cdc2aAt mutants of arabidopsis.
AB  - During plant development, cell division events are coordinately regulated,
      leading to specific growth patterns. Experimental evidence indicates that the
      morphogenetic controls that act at the vegetative plant growth stage are flexible
      and tolerate distortions in patterns and frequencies of cell division. To address
      questions concerning the relationship between cell division and embryo formation,
      a novel experimental approach was used. The frequencies of cell division were
      reduced exclusively during embryo development of Arabidopsis by the expression of
      a dominant cdc2a mutant. The five independent transgenic lines with the highest
      levels of the mutant cdc2a affected embryo formation. In the C13 line, seeds
      failed to germinate. The C1, C5 and C12 lines displayed a range of distortions on
      the apical-basal embryo pattern. In the C3 line, the shoot apical meristem of the
      seedlings produced leaves defective in growth and with an incorrect phyllotactic
      pattern. The results demonstrate that rates of cell division do not dictate
      cellular differentiation of embryos. Nevertheless, whereas cell divisions are
      uncoupled from vegetative development, they are instrumental in elaborating
      embryo structures and modulating embryo and seedling morphogenesis.

PMID- 10929108
TI  - Technical advance: simultaneous analysis of metabolites in potato tuber by gas
      chromatography-mass spectrometry.
AB  - A new method is presented in which gas chromatography coupled to mass
      spectrometry (GC-MS) allows the quantitative and qualitative detection of more
      than 150 compounds within a potato tuber, in a highly sensitive and specific
      manner. In contrast to other methods developed for metabolite analysis in plant
      systems, this method represents an unbiased and open approach that allows the
      detection of unexpected changes in metabolite levels. Although the method
      represents a compromise for a wide range of metabolites in terms of extraction,
      chemical modification and GC-MS analysis, for 25 metabolites analysed in detail
      the recoveries were found to be within the generally accepted range of 70-140%.
      Further, the reproducibility of the method was high: the error occurring in the
      analysis procedures was found to be less than 6% for 30 out of 33 compounds
      tested. Biological variability exceeded the systematic error of the analysis by a
      factor of up to 10. The method is also suited for upscaling, potentially allowing
      the simultaneous analysis of a large number of samples. As a first example this
      method has been applied to soil- and in vitro-grown tubers. Due to the
      simultaneous analysis of a wide range of metabolites it was immediately apparent
      that these systems differ significantly in their metabolism. Furthermore, the
      parallel insight into many pathways allows some conclusions to be drawn about the
      underlying physiological differences between both tuber systems. As a second
      example, transgenic lines modified in sucrose catabolism or starch synthesis were
      analysed. This example illustrates the power of an unbiased approach to detecting
      unexpected changes in transgenic lines.

PMID- 10929109
TI  - Technical advance: the DNA-binding activity of gal4 is inhibited by methylation
      of the gal4 binding site in plant chromatin.
AB  - Derivatives of the Saccharomyces cerevisiae transcription factor Gal4 which act
      as effective transcription activators in yeast, Drosophila, mammalian cells and
      plant protoplasts are shown to direct expression from a GUS reporter construct
      when expressed in transgenic tobacco. However, in comparison to 35S-GUS controls,
      Gal4-mediated expression of the reporter gene was relatively weak and extremely
      variable. GUS expression was lost as plants matured and it was almost
      undetectable in most of their progeny. Gal4-mediated gene expression could be
      restored by treating tissues with 5-aza-cytidine, implicating cytosine
      methylation in the loss of Gal4-mediated expression. Restoration of reporter
      expression was not accompanied by an increase in steady-state levels of the
      activator transcript. We propose that the DNA-binding activity of Gal4 is
      sensitive to methylation of its binding site in plant chromatin. The Gal4-DNA co
      crystal predicts that 5-methylcytosine at either of the outer two positions of
      the binding site will effectively prevent Gal4 binding. We show that these
      positions become extensively methylated in transgenic plants and that methylation
      of Gal4-binding sites interferes with Gal4 binding in vitro. These observations
      suggest that the Gal4 DNA-binding domain is intrinsically sensitive to cytosine
      methylation and that, despite the success of Gal4-based expression systems in
      yeast and Drosophila, Gal4 is not ideal for use in plant gene expression
      technology.

PMID- 10929110
TI  - In vivo targeting of a sunflower oil body protein in yeast secretory (sec)
      mutants.
AB  - A sunflower oleosin was expressed in yeast to study the in vivo insertion of the
      protein into the endoplasmic reticulum (ER) and subsequent transfer to lipid
      bodies. The oleosin cDNA was expressed in a range of yeast secretory (sec)
      mutants to determine the precise targeting pathway of the oleosin to the ER.
      Subcellular fractionation experiments indicated that the signal recognition
      particle (SRP) is required for oleosin targeting to the ER and hence subsequent
      deposition on the lipid bodies in vivo. The expression of oleosin in a range of
      sec61 mutant alleles confirmed the role of the SEC61 translocon in insertion of
      oleosin into the ER membrane, as well as indicating an unusual
      substrate/translocon interaction for one particular allele (sec61-3).
      Mistargeting of the oleosin due to impaired SRP function resulted in enhanced
      proteolysis of the plant protein in the transformed yeast, as determined by pulse
      chase analysis. These data therefore provide the first in vivo evidence for the
      SRP-dependent targeting of the oleosin to the ER, and the subsequent requirement
      for a functional SEC61 translocon to mediate the correct insertion of the protein
      into the membrane.

PMID- 10929111
TI  - The roles of three functional sulphate transporters involved in uptake and
      translocation of sulphate in Arabidopsis thaliana.
AB  - To investigate the uptake and long-distance translocation of sulphate in plants,
      we have characterized three cell-type-specific sulphate transporters, Sultr1;1,
      Sultr2;1 and Sultr2;2 in Arabidopsis thaliana. Heterologous expression in the
      yeast sulphate transporter mutant indicated that Sultr1;1 encodes a high-affinity
      sulphate transporter (Km for sulphate 3.6 +/- 0.6 microM), whereas Sultr2;1 and
      Sultr2;2 encode low-affinity sulphate transporters (Km for sulphate 0.41 +/- 0.07
      mM and >/= 1.2 mM, respectively). In Arabidopsis plants expressing the fusion
      gene construct of the Sultr1;1 promoter and green fluorescent protein (GFP), GFP
      was localized in the lateral root cap, root hairs, epidermis and cortex of roots.
      beta-glucuronidase (GUS) expressed with the Sultr2;1 promoter was specifically
      accumulated in the xylem parenchyma cells of roots and leaves, and in the root
      pericycles and leaf phloem. Expression of the Sultr2;2 promoter-GFP fusion gene
      showed specific localization of GFP in the root phloem and leaf vascular bundle
      sheath cells. Plants continuously grown with low sulphate concentrations
      accumulated high levels of Sultr1;1 and Sultr2;1 mRNA in roots and Sultr2;2 mRNA
      in leaves. The abundance of Sultr1;1 and Sultr2;1 mRNA was increased remarkably
      in roots by short-term stress caused by withdrawal of sulphate. Addition of
      selenate in the sulphate-sufficient medium increased the sulphate uptake
      capacity, tissue sulphate content and the abundance of Sultr1;1 and Sultr2;1 mRNA
      in roots. Concomitant decrease of the tissue thiol content after selenate
      treatment was consistent with the suggested role of glutathione (GSH) as a
      repressive effector for the expression of sulphate transporter genes.

PMID- 10929112
TI  - Expression of the Fusarium resistance gene I-2 colocalizes with the site of
      fungal containment.
AB  - The tomato resistance gene I-2 is one of at least six members of a gene family
      that are expressed at low levels in the roots, stems and leaves of young tomato
      plants. Plants transformed with constructs containing a functional I-2 promoter
      fused to the beta-glucuronidase (GUS) reporter gene were used in detailed
      expression studies. Highest GUS activity was found in stems of young tomato
      plants. Histochemical analysis revealed that the I-2 promoter drives expression
      of the reporter gene in vascular tissue of fruits, leaves, stems and mature
      roots. In younger roots, expression was most abundant at the base of lateral root
      primordia. Microscopical analysis of young tomato plants revealed expression in
      tissue surrounding the xylem vessels. We show that in resistant plants, fungal
      growth into this region of the vascular tissue is prevented, suggesting a
      correlation with the I-2-mediated resistance response.

PMID- 10929113
TI  - A novel composite locus of Arabidopsis encoding two polypeptides with
      metabolically related but distinct functions in lysine catabolism.
AB  - Both plants and animals catabolize lysine via saccharopine by two consecutive
      enzymes, lysine-ketoglutarate reductase (LKR) and saccharopine dehydrogenase
      (SDH), which are linked on a single polypeptide. We recently demonstrated that
      Arabidopsis plants possess not only a bifunctional LKR/SDH but in addition a
      monofunctional SDH enzyme. We also speculated that these two enzymes may be
      controlled by a single gene (G. Tang et al. Plant Cell, 1997, 9, 1305-1316). By
      expressing several epitope-tagged and GUS reporter constructs, we demonstrate in
      the present study that the Arabidopsis monofunctional SDH is encoded by a
      distinct gene, which is, however, nested entirely within the coding and 3' non
      coding regions of the larger bifunctional LKR/SDH gene. The entire open reading
      frame of the monofunctional SDH gene, as well as some components of its promoter,
      are also parts of the translated coding sequence of the bifunctional LKR/SDH
      gene. These special structural characteristics, combined with the fact that the
      two genes encode simultaneously two metabolically related but distinct enzymes,
      render the LKR/SDH locus a novel type of a composite locus. Not all plant species
      possess an active monofunctional SDH gene and the production of this enzyme is
      correlated with an increased flux of lysine catabolism. Taken together, our
      results suggest that the composite LKR/SDH locus serves to control an efficient,
      highly regulated flux of lysine catabolism

PMID- 10929114
TI  - Conversion of compatible plant-pathogen interactions into incompatible
      interactions by expression of the Pseudomonas syringae pv. syringae 61 hrmA gene
      in transgenic tobacco plants.
AB  - The hrmA gene from Pseudomonas syringae pv. syringae has previously been shown to
      confer avirulence on the virulent bacterium P. syringae pv. tabaci in all
      examined tobacco cultivars. We expressed this gene in tobacco plants under the
      control of the tobacco Delta0. 3 TobRB7 promoter, which is induced upon nematode
      infection in tobacco roots (Opperman et al. 1994, Science, 263, 221-223). A basal
      level of hrmA expression in leaves of transgenic plants activated the expression
      of pathogenesis-related genes, and the transgenic plants exhibited high levels of
      resistance to multiple pathogens: tobacco vein mottling virus, tobacco etch
      virus, black shank fungus Phytophthora parasitica, and wild fire bacterium
      Pseudomonas syringae pv. tabaci. However, the hrmA transgenic plants were not
      significantly more resistant to root-knot nematodes. Our results suggest a
      potential use of controlled low-level expression of bacterial avr genes, such as
      hrmA, in plants to generate broad-spectrum resistance to bacterial, fungal and
      viral pathogens.

PMID- 10929115
TI  - Sense transformation reveals a novel role for class I beta-1, 3-glucanase in
      tobacco seed germination.
AB  - 'Coat-enhanced' seed dormancy of many dicotyledonous species, including tobacco,
      is released during after-ripening. Rupture of the endosperm, which is the
      limiting step in tobacco seed germination, is preceded by induction of class I
      beta-1,3-glucanase (betaGLU I) in the micropylar endosperm where the radicle will
      penetrate. Treating after-ripened tobacco seeds with abscisic acid (ABA) delays
      endosperm rupture and inhibits betaGLU I induction. Sense transformation with a
      chimeric ABA-inducible betaGLU I transgene resulted in over-expression of betaGLU
      I in seeds and promoted endosperm rupture of mature seeds and of ABA-treated
      after-ripened seeds. Taken together, these results provide direct evidence that
      betaGLU I contributes to endosperm rupture. Over-expression of betaGLU I during
      germination also replaced the effects of after-ripening on endosperm rupture.
      This suggests that regulation of betaGLU I by ABA signalling pathways might have
      a key role in after-ripening.

PMID- 10929117
TI  - Comparative physical mapping of segments of the genome of Brassica oleracea var.
      alboglabra that are homoeologous to sequenced regions of chromosomes 4 and 5 of
      Arabidopsis thaliana.
AB  - Due to their relatedness to Arabidopsis thaliana (Arabidopsis), the cultivated
      Brassica species represent the first group of crops with which to evaluate
      comparative genomics approaches to understanding biological processes and
      manipulating traits. We have constructed a high-quality binary BAC library (JBo)
      from genomic DNA of Brassica oleracea var. alboglabra, in order to underpin such
      investigations. Using the Arabidopsis genome sequence and clones from the JBo
      library, we have analysed aspects of gene conservation and microsynteny between a
      222 kb region of the genome of Arabidopsis and homoeologous segments of the
      genome of B. oleracea. All 19 predicted genes tested were found to hybridize to
      clones in the JBo library, indicating a high level of gene conservation. Further
      analyses and physical mapping with the BAC clones identified allowed us to
      construct clone contig maps and analyse in detail the gene content and
      organization in the set of paralogous segments identified in the genome of B.
      oleracea. Extensive divergence of gene content was observed, both between the B.
      oleracea paralogous segments and between them and their homoeologous segment
      within the genome of Arabidopsis. However, the genes present show highly
      conserved collinearity with their orthologues in the genome of Arabidopsis. We
      have identified one example of a Brassica gene in a non-collinear position and
      one rearrangement. Some of the genes not present in the discernible homoeologous
      regions appear to be located elsewhere in the B. oleracea genome. The
      implications of our findings for comparative map-based cloning of genes from crop
      species are discussed.

PMID- 10929116
TI  - Phytochrome A resets the circadian clock and delays tuber formation under long
      days in potato.
AB  - Transgenic potatoes (Solanum tuberosum) with either increased (sense
      transformants) or reduced (antisense transformants) phytochrome A (phyA) levels
      were used, in combination with specific light treatments, to investigate the
      involvement of phyA in the perception of signals that entrain the circadian
      clock. Far-red or far-red plus red light treatments given during the night reset
      the circadian rhythm of leaf movements in wild-type plants and phyA over
      expressors, but had little effect in phyA under-expressors. Far-red light was
      also able to reset the rhythm of leaf movement in wild-type Arabidopsis thaliana
      but was not effective in mutants without phyA. Blue light was necessary to reset
      the rhythm in phyA-deficient potato plants. Resetting of the rhythm by far-red
      plus red light was only slightly affected in transgenic plants with reduced
      levels of phytochrome B. The production of tubers was delayed by day extensions
      with far-red plus red light, but this effect was reduced in transgenic lines
      deficient in phyA. We conclude that phyA is involved in resetting the circadian
      clock controlling leaf movements and in photoperiod sensing in light-grown potato
      plants.

PMID- 10929118
TI  - Proton extrusion is an essential signalling component in the HR of epidermal
      single cells in the barley-powdery mildew interaction.
AB  - We propose a model for activation of the epidermal cell hypersensitive response
      (HR) in the barley/powdery mildew interaction. The model suggests that the plasma
      membrane proton pump (H+-ATPase) of epidermal cells is activated following
      penetration by an avirulent powdery mildew fungus. This will cause an
      acidification of the apoplast towards the mesophyll cells, thereby activating
      generation of H2O2 from the mesophyll, which subsequently triggers the epidermal
      cell to undergo HR. The model is supported by the following data: (1) the
      earliest HR-related H2O2 is found in the attachment zones between the epidermal
      cell and underlying mesophyll cells; (2) scavenger treatment reduces HR; (3)
      treatment of leaves with low-pH (3.5) citrate and succinate buffers causes more
      cells to undergo HR in the compatible interaction, while treatment with the same
      buffers at pH 5.5 reduces the number of HR-cells in the incompatible interaction;
      (4) race-specific proton extrusion is observed underneath epidermal tissue
      detached from leaves inoculated 15 h earlier; and (5) treatment of leaves with
      fusicoccin, an activator of the plasma membrane H+-ATPase, increases the number
      of HR-cells in the compatible interaction.

PMID- 10929119
TI  - Replication of chloroplast, mitochondrial and nuclear DNA during growth of
      unirradiated and UVB-irradiated Arabidopsis leaves.
AB  - Replication of Arabidopsis nuclear, mitochondrial and chloroplast DNA (ncDNA,
      mtDNA, cpDNA) was assayed by measuring respective changes in copies per leaf,
      employing quantitative PCR (QPCR) analysis with genome-specific primer pairs. All
      three genomes showed parallel increases during growth of cotyledons and 5th
      leaves in planta, maintaining approximately 13 mtDNA copies and 280 cpDNA copies
      per haploid nuclear genome. Detached 5th leaves, which showed good growth and DNA
      replication on agar plates, were irradiated at (DNA-effective) UV-B fluences of
      1.3-5.0 kJ m-2 and incubated under blue (photorepair-active) plus gold light or
      gold light only. Under blue light, replication of all genomes after all UV
      fluences was approximately as efficient as replication in unirradiated leaves. UV
      irradiated leaves showed little growth under gold light only; 5 kJ m-2 stopped
      replication of all three genomes, 2.5 kJ m-2 stopped only cpDNA replication, and
      1.3 kJ m-2 only delayed cpDNA replication. Immunoassays showed that 5 kJ m-2
      induced about 1.2 cyclobutane pyrimidine dimers and 0.1 [6-4]photoproducts per
      kbp of bulk DNA, and that both photoproducts were completely removed during 2-3
      days under blue light, suggesting efficient photorepair of at least ncDNA and
      cpDNA. The evidence for efficient photorepair of organellar DNA contrasts with
      previous studies of irradiated 5-day-old seedlings, and with the apparent absence
      of Arabidopsis photolyases bearing transit peptides.

PMID- 10929120
TI  - Cell-type-specific calcium responses to drought, salt and cold in the Arabidopsis
      root.
AB  - Little is known about the signalling processes involved in the response of roots
      to abiotic stresses. The Arabidopsis root is a model system of root anatomy with
      a simple architecture and is amenable to genetic manipulation. Although it is
      known that the root responds to cold, drought and salt stress with increases in
      cytoplasmic free calcium, there is currently no information about the role(s) of
      the functionally diverse cell types that comprise the root. Transgenic
      Arabidopsis with enhancer-trapped GAL4 expression in specific cell types was used
      to target the calcium reporting protein, aequorin, fused to a modified yellow
      fluorescent protein (YFP). The luminescence output of targeted aequorin enabled
      in vivo measurement of changes in cytosolic free calcium concentrations
      ([Ca2+]cyt) in specific cell types during acute cold, osmotic and salt stresses.
      In response to an acute cold stress, all cell types tested as well as plants
      constitutively expressing aequorin displayed rapid [Ca2+]cyt peaks. However,
      there were significant quantitative differences between different cell types in
      terms of their response to cold stress, osmotic stress (440 mM mannitol) and salt
      stress (220 mM NaCl), implying specific roles for certain cell types in the
      detection and/or response to these stimuli. In response to osmotic and salt
      stress, the endodermis and pericycle displayed prolonged oscillations in
      cytosolic calcium that were distinct from the responses of the other cell types
      tested. Targeted expression of aequorin circumvented the technical difficulties
      involved in fluorescent dye injection as well as the lack of cell specificity of
      constitutively expressed aequorin, and revealed a new level of complexity in root
      calcium signalling.

PMID- 10929121
TI  - Transgenic tobacco plants co-expressing Agrobacterium iaa and ipt genes have wild
      type hormone levels but display both auxin- and cytokinin-overproducing
      phenotypes.
AB  - Transgenic tobacco lines simultaneously expressing the Agrobacterium iaaM, iaaH
      and ipt genes, obtained by crossing lines expressing ipt with lines expressing
      iaaM and iaaH, were used to study in planta interactions between auxin and
      cytokinins. All phenotypic traits of the respective parental lines characteristic
      of cytokinin and auxin overproduction were present in the cross. Indole-3-acetic
      acid (IAA) and combined zeatin riboside (ZR) and zeatin riboside-5'-monophosphate
      (ZRMP) contents were analysed by mass spectrometry in young, developing leaves
      from the cross, the parental lines and the wild type. Unexpectedly, hormone
      levels in the cross were very similar to wild-type levels. Thus IAA levels in the
      cross were much lower throughout vegetative development than in the parental IAA
      overproducing line, although expression of the bacterial IAA biosynthesis genes
      was not reduced. The results suggest that effects on apical dominance,
      adventitious root formation, leaf morphology and other traits commonly +/-
      associated with IAA and cytokinin overproduction, and observed in the iaa E ipt
      cross, cannot be explained solely by analysis of auxin and cytokinin contents in
      individual organs. As traits associated with both hormones are expressed in close
      spatial and temporal proximity, it is likely that cellular resolution of hormone
      contents is essential to explain physiological responses to auxins and
      cytokinins.

PMID- 10929122
TI  - Developmental and light-dependent regulation of a phloem-localised K+ channel of
      Arabidopsis thaliana.
AB  - K+ channels in plants can currently be classified into six families with
      individual members being involved in nutrient uptake, loading of the xylem and
      the physiology of stomatal movement. In this study we have focused on akt2/3.
      This K+ channel, as shown by GUS-expression analysis, is expressed in the phloem
      and xylem of the aerial parts of Arabidopsis thaliana. Northern blot analyses
      revealed the highest akt2/3-concentrations in the flower stalk, followed by the
      leaf, flower and stem. During the light period (8 am to 4 pm), transcripts
      reached a peak around noon (11 am), decayed to almost 50% in the afternoon and
      reached a low background level in the following dark period. In continuous
      darkness, however, the K+ channel mRNA content had already decreased beyond the
      background level by noon. In leaves and flower stalk, the light-induced
      transcription of akt2/3 was suppressed by CO2-free air, indicating that gene
      activity is under the control of photosynthates. Additionally, when rosette
      leaves were illuminated and flower stalks shaded, akt2/3-mRNA transcription was
      still inhibited in the shaded region. This indicates that channel gene activation
      is sensitive to photosynthesis-derived factors from neighboring cells rather than
      factors mobile in the phloem. We propose that the coupling between sugar
      production and allocation involves the photosynthate- and light-dependent phloem
      K+ channel AKT2/3.

PMID- 10929123
TI  - Efficient insertion mutagenesis of Arabidopsis by tissue culture-induced
      activation of the tobacco retrotransposon Tto1.
AB  - The tobacco retrotransposon Tto1 is one of a few active retrotransposons in
      plants. Its transposition is activated by tissue culture and is primarily
      regulated at the transcriptional level. Here we demonstrate that Tto1 introduced
      in Arabidopsis is also activated by tissue culture. Transcription of Tto1 was
      induced by tissue culture and driven by its LTR promoter. Transposed copies of
      Tto1 were observed in almost all of the plants regenerated from the explants
      cultured for only 1 week. A total of 255 independent regenerated lines have been
      produced, and the average copy number of transposed Tto1 in these lines is
      estimated to be 3.2. Sequences flanking Tto1 were amplified by thermal asymmetric
      interlaced (TAIL)-PCR. Of 165 independent amplified products, 123 showed
      significant homology to known genes or hypothetical protein genes. The insertion
      sites of Tto1 are spread over all chromosomes and the target site sequence shows
      moderate consensus. Taken together, these results indicate that Tto1 can be used
      as a tool for efficient insertion mutagenesis of Arabidopsis which is especially
      suitable as a reverse genetics system.

PMID- 10929124
TI  - Salicylic acid is not required for Cf-2- and Cf-9-dependent resistance of tomato
      to Cladosporium fulvum.
AB  - Tomato leaves or cotyledons expressing the Cf-2 or Cf-9 Cladosporium fulvum
      resistance genes induce salicylic acid (SA) synthesis following infiltration with
      intercellular washing fluid (IF) containing the fungal peptide elicitors Avr2 and
      Avr9. We investigated whether SA was required for Cf gene-dependent resistance.
      Tomato plants expressing the bacterial gene nahG, encoding salicylate
      hydroxylase, did not accumulate SA in response to IF infiltration but remained
      fully resistant to C. fulvum. NahG Cf0 plants were as susceptible to C. fulvum as
      wild-type Cf0. Neither free nor conjugated salicylic acid accumulated in IF
      infiltrated Cf2 and Cf9 NahG leaves and cotyledons but conjugated catechol did
      accumulate. The Cf-9-dependent necrotic response to IF was prevented in NahG
      plants and replaced by a chlorotic Cf-2-like response. SA also potentiated Cf-9
      mediated necrosis in IF-infiltrated wild-type leaves. In contrast, the Cf-2
      dependent IF response was retained in NahG leaves and chlorosis was more
      pronounced than in the wild-type. The distribution of cell death between
      different cell types was altered in both Cf2 and Cf9 NahG leaves after IF
      injection. IF-induced accumulation of three SA-inducible defence-related genes
      was delayed and reduced but not abolished in NahG Cf2 and Cf9 leaves and
      cotyledons. NahG Tm-22 tomato showed increased hypersensitive response (HR)
      lesion size upon TMV infection, as observed in TMV-inoculated N gene-containing
      NahG tobacco plants.

PMID- 10929125
TI  - Over-expression of a single Ca2+-dependent protein kinase confers both cold and
      salt/drought tolerance on rice plants.
AB  - A rice gene encoding a calcium-dependent protein kinase (CDPK), OsCDPK7, was
      induced by cold and salt stresses. To elucidate the physiological function of
      OsCDPK7, we generated transgenic rice plants with altered levels of the protein.
      The extent of tolerance to cold and salt/drought stresses of these plants
      correlated well with the level of OsCDPK7 expression. Therefore, OsCDPK7 was
      shown to be a positive regulator commonly involved in the tolerance to both
      stresses in rice. Over-expression of OsCDPK7 enhanced induction of some stress
      responsive genes in response to salinity/drought, but not to cold. Thus, it was
      suggested that the downstream pathways leading to the cold and salt/drought
      tolerance are different from each other. It seems likely that at least two
      distinct pathways commonly use a single CDPK, maintaining the signalling
      specificity through unknown post-translational regulation mechanisms. These
      results demonstrate that simple manipulation of CDPK activity has great potential
      with regard to plant improvement.

PMID- 10929126
TI  - Induction of dwarfism in transgenic Solanum dulcamara by over-expression of a
      gibberellin 20-oxidase cDNA from pumpkin.
AB  - The gibberellin (GA) 20-oxidase (CmGA20ox1) from immature pumpkin seed produces
      predominantly inactive tricarboxylic acid GAs. We expressed CmGA20ox1 under the
      control of the CaMV 35S promoter in Solanum dulcamara to assess the usefulness of
      this gene for reducing GA content in transgenic plants. All transgenic plants
      obtained were semi-dwarfs with smaller, deep-green leaves and highly pigmented
      stems compared to the wild-type. Such transformants flowered earlier than the
      wild-type plants and produced more fruit and more seeds per fruit. The transgene
      was efficiently expressed, producing high levels of CmGA20ox1 transcript and
      protein. Furthermore, the concentration of GA(1) was reduced in leaves of the
      transformants to approximately 20% or less of that in the wild-type and to about
      40% or less in stems. The concentrations of other 13-hydroxylated GAs were also
      reduced, except for the tricarboxylic acid, GA(17), which accumulated in the
      transformants due to 13-hydroxylation of GA(25). By contrast, the concentrations
      of non-13-hydroxylated GAs, GA(4) and GA(34), were not consistently reduced,
      indicating that the effect of expressing the pumpkin gene may not be predictable.
      Transcript abundance for a native GA 20-oxidase gene was higher in the leaves and
      stems of S. dulcamara transformed with the pumpkin gene than in wild-type,
      reflecting the feedback control of 20-oxidase gene expression that serves as a
      homeostatic mechanism for GAs.

PMID- 10929127
TI  - Multiple levels of tobacco WIPK activation during the induction of cell death by
      fungal elicitins.
AB  - Three protein kinases of 48, 44 and 40 kDa are activated at different stages in
      tobacco cells treated with fungal elicitins. Previously we demonstrated that the
      rapidly activated 48 kDa protein kinase is encoded by SIPK. Here we report that
      the elicitin-activated 44 kDa kinase is encoded by WIPK. Activation of this
      kinase occurred 2-4 h after elicitin treatment and was preceded by dramatic
      increases in WIPK mRNA and protein levels. Studies using actinomycin D and
      cycloheximide demonstrated that de novo transcription and translation were
      required for this activation of the kinase activity. Strikingly, the kinetics of
      WIPK activation following elicitin treatment correlated with the onset of
      hypersensitive response (HR)-like cell death. Moreover, staurosporine and K-252a,
      two Ser/Thr protein kinase inhibitors that blocked WIPK activation, suppressed
      cell death. The timing for elicitin-treated cells to commit to a death program
      correlated with the appearance of high levels of WIPK activity. These correlative
      data suggest that WIPK may play a role during HR development in tobacco.
      Interestingly, a fungal cell-wall elicitor that does not cause cell death induced
      WIPK mRNA and protein to similar levels as those observed with the elicitins.
      However, no corresponding increase in WIPK activity was detected. Thus WIPK
      appears to be controlled at multiple levels.

PMID- 10929128
TI  - Vascular invasion routes and systemic accumulation patterns of tobacco mosaic
      virus in Nicotiana benthamiana.
AB  - Plant viruses must enter the host vascular system in order to invade the young
      growing parts of the plant rapidly. Functional entry sites into the leaf vascular
      system for rapid systemic infection have not been determined for any plant/virus
      system. Tobacco mosaic virus (TMV) entry into minor, major and transport veins
      from non-vascular cells of Nicotiana benthamiana in source tissue and its exit
      from veins in sink tissue was studied using a modified virus expressing green
      fluorescent protein (GFP). Using a surgical procedure that isolated specific leaf
      and stem tissues from complicating vascular tissues, we determined that TMV could
      enter minor, major or transport veins directly from non-vascular cells to produce
      a systemic infection. TMV first accumulated in abaxial or external phloem
      associated cells in major veins and petioles of the inoculated leaf and stems
      below the inoculated leaf. It also initially accumulated exclusively in internal
      or adaxial phloem-associated cells in stems above the inoculated leaf and
      petioles or major veins of sink leaves. This work shows the functional
      equivalence of vein classes in source leaves for entry of TMV, and the lack of
      equivalence of vein classes in sink leaves for exit of TMV. Thus, the
      specialization of major veins for transport rather than loading of
      photoassimilates in source tissue does not preclude virus entry. During
      transport, the virus initially accumulates in specific vascular-associated cells,
      indicating that virus accumulation in this tissue is highly regulated. These
      findings have important implications for studies on the identification of
      symplasmic domains and host macromolecule vascular transport.

PMID- 10929129
TI  - Ectopic expression of a tomato 9-cis-epoxycarotenoid dioxygenase gene causes over
      production of abscisic acid.
AB  - The tomato mutant notabilis has a wilty phenotype as a result of abscisic acid
      (ABA) deficiency. The wild-type allele of notabilis, LeNCED1, encodes a putative
      9-cis-epoxycarotenoid dioxygenase (NCED) with a potential regulatory role in ABA
      biosynthesis. We have created transgenic tobacco plants in which expression of
      the LeNCED1 coding region is under tetracycline-inducible control. When leaf
      explants from these plants were treated with tetracycline, NCED mRNA was induced
      and bulk leaf ABA content increased by up to 10-fold. Transgenic tomato plants
      were also produced containing the LeNCED1 coding region under the control of one
      of two strong constitutive promoters, either the doubly enhanced CaMV 35S
      promoter or the chimaeric 'Super-Promoter'. Many of these plants were wilty,
      suggesting co-suppression of endogenous gene activity; however three
      transformants displayed a common, heritable phenotype that could be due to
      enhanced ABA biosynthesis, showing increased guttation and seed dormancy. Progeny
      from two of these transformants were further characterized, and it was shown that
      they also exhibited reduced stomatal conductance, increased NCED mRNA and
      elevated seed ABA content. Progeny of one transformant had significantly higher
      bulk leaf ABA content compared to the wild type. The increased seed dormancy was
      reversed by addition of the carotenoid biosynthesis inhibitor norflurazon. These
      data provide strong evidence that NCED is indeed a key regulatory enzyme in ABA
      biosynthesis in leaves, and demonstrate for the first time that plant ABA content
      can be increased through manipulating NCED.

PMID- 10929130
TI  - Fungal cell wall phosphomannans facilitate the toxic activity of a plant PR-5
      protein.
AB  - Osmotin is a plant PR-5 protein. It has a broad spectrum of antifungal activity,
      yet also exhibits specificity for certain fungal targets. The structural bases
      for this specificity remain unknown. We show here that full sensitivity of
      Saccharomyces cerevisiae cells to the PR-5 protein osmotin is dependent on the
      function of MNN2, MNN4 and MNN6. MNN2 is an alpha-1, 2-mannosyltransferase
      catalyzing the addition of the first mannose to the branches on the poly l,6
      mannose backbone of the outer chain of cell wall N-linked mannans. MNN4 and MNN6
      are required for the transfer of mannosylphosphate to cell wall mannans. Null
      mnn2, mnn4 or mnn6 mutants lack phosphomannans and are defective in binding
      osmotin to the fungal cell wall. Both antimannoprotein antibody and the cationic
      dye alcian blue protect cells against osmotin cytotoxicity. MNN1 is an alpha-1,3
      mannosyltransferase that adds the terminal mannose to the outer chain branches of
      N-linked mannan, masking mannosylphosphate. Null mnn1 cells exhibit enhanced
      osmotin binding and sensitivity. Several cell wall mannoproteins can bind to
      immobilized osmotin, suggesting that their polysaccharide constituent determines
      osmotin binding. Our results demonstrating a causal relationship between cell
      surface phosphomannan and the susceptibility of a yeast strain to osmotin suggest
      that cell surface polysaccharides of invading pathogens control target
      specificity of plant PR-5 proteins.

PMID- 10929131
TI  - The Cytokinin-hypersensitive genes of Arabidopsis negatively regulate the
      cytokinin-signaling pathway for cell division and chloroplast development.
AB  - We isolated Arabidopsis thaliana mutants that respond more sensitively than the
      wild type to cytokinins. The calli produced from the mutants exhibit typical
      cytokinin responses, including rapid proliferation and chloroplast development in
      response to lower levels of cytokinins than in the wild type. The mutations are
      recessive and belong to two complementation groups designated ckh1 and ckh2 for
      cytokinin-hypersensitive. CKH1 and CKH2 were mapped to the top of chromosome I
      and the middle of chromosome II, respectively. The cytokinin levels in these
      mutants were not increased. We speculate that the CKH1 and CKH2 gene products
      negatively regulate the signaling pathway leading from cytokinin perception to
      cell proliferation and chloroplast development.

PMID- 10929132
TI  - DNA-interactions and nuclear localisation of the chromosomal HMG domain protein
      SSRP1 from maize.
AB  - The structure-specific recognition protein 1 (SSRP1) is a member of the protein
      family containing a high mobility group (HMG) domain DNA-binding motif. We have
      functionally characterised the 71.4 kDa Zm-SSRP1 protein from maize. The
      chromatin-associated Zm-SSRP1 is detected by immunoblot analysis in maize leaves,
      kernels and suspension culture cells, but not in roots. Mediated by its HMG
      domain, recombinant Zm-SSRP1 interacts structure-specifically with supercoiled
      DNA and DNA minicircles when compared with linear DNA. In linear duplex DNA, the
      protein does not recognise a specific sequence, but it binds preferentially to
      sequences containing the deformable dinucleotide TG, as demonstrated by a random
      oligonucleotide selection experiment. Zm-SSRP1 modulates DNA structure by bending
      the target sequence, since it promotes the circularisation of short DNA fragments
      in the presence of DNA ligase. Moreover, Zm-SSRP1 facilitates the formation of
      nucleoprotein structures, as measured using the bacterial site-specific beta
      mediated recombination reaction. Analysis of the subcellular localisation of
      various SSRP1-GFP fusions revealed that, in contrast to HMG domain transcription
      factors, the nuclear localisation sequence of Zm-SSRP1 is situated within a 20
      amino acid residue region adjacent to the HMG domain rather than within the DNA
      binding domain. The results are discussed in the context of the likely function
      of SSRP1 proteins in transcription and replication.

PMID- 10929133
TI  - Suppression of cell expansion by ectopic expression of the Arabidopsis SUPERMAN
      gene in transgenic petunia and tobacco.
AB  - Molecular and genetic analyses have shown that the Arabidopsis thaliana gene
      SUPERMAN (SUP) has at least two functions in Arabidopsis flower development. SUP
      is necessary to control the correct distribution of cells with either a stamen or
      carpel fate, and is essential for proper outgrowth of the ovule outer integument.
      Both these functions indicate a role for SUP in cell proliferation. To study the
      function of the Arabidopsis SUP gene in more detail, we over-expressed the SUP
      gene in petunia and tobacco in a tissue-specific manner. The petunia FLORAL
      BINDING PROTEIN 1 (FBP1) gene promoter was used to restrict the expression of SUP
      to petals and stamens. The development of petals and stamens was severely
      affected in both petunia and tobacco plants over-expressing SUP. Petals remained
      small and did not unfold, resulting in closed flowers. Stamen filaments were thin
      and very short. Detailed analysis of these floral organs from the petunia
      transformants showed that cell expansion was dramatically reduced without
      affecting cell division. These results reveal a novel activity for SUP as a
      regulator of cell expansion.

PMID- 10929134
TI  - Quantitative nature of the Prolamin-box, ACGT and AACA motifs in a rice glutelin
      gene promoter: minimal cis-element requirements for endosperm-specific gene
      expression.
AB  - The -197 bp promoter of the rice seed storage protein gene, GluB-1, is capable of
      conferring endosperm-specific gene expression. This proximal 5' flanking region
      contains four motifs, GCN4, AACA, ACGT and Prolamin-box, which are conserved in
      many seed storage protein genes. We previously showed that multiple copies of
      GCN4 conferred endosperm expression pattern when fused to the -46 core promoter
      of CaMV 35S. In this paper we demonstrate, using a similar approach, that tandem
      repeated copies of any of the other three motifs are unable to direct expression
      in seeds as well as other tissues of transgenic rice plants. Mutational analysis
      of individual motifs in the -197 bp promoter resulted in remarkable reductions in
      promoter activity. These results indicate that the GCN4 motif acts as an
      essential element determining endosperm-specific expression and that the AACA,
      ACGT and Prolamin-box are involved in quantitative regulation of the GluB-1 gene.
      A set of gain-of-function experiments using transgenic rice showed that either
      the Prolamin-box or AACA, although often coupled with GCN4 in many genes, is
      insufficient to form a functional promoter unit with GCN4, whereas a combination
      of GCN4, AACA and ACGT motifs was found sufficient to confer a detectable level
      of endosperm expression. Taken together, our results provide direct insight into
      the importance of combinatorial interplay between cis-elements in regulating the
      expression of seed storage protein genes.

PMID- 10929135
TI  - FLP-mediated recombination for use in hybrid plant production.
AB  - We have studied the feasibility in Arabidopsis of using a site-specific
      recombination system FLP/FRT, from the 2 microm plasmid of yeast, for making
      plant hybrids. Initially, Arabidopsis plants expressing the FLP site-specific
      recombinase were crossed with plants transformed with a vector containing
      kanamycin-resistance gene (npt) flanked by FRT sites, which also served to
      separate the CaMV35S promoter from a promoterless gusA. Hybrid progeny were
      tested for excision of the npt gene and the positioning of 35S promoter proximal
      to gusA. GUS activity was observed in the progeny of all crosses, but not in the
      progeny derived from the self-pollinated homozygous parents. We then induced male
      sterility in Arabidopsis plants using the antisense expression of a pollen- and
      tapetum-specific gene, bcp1, flanked by FRT sites. Upon cross-pollination of
      flowers on the same male-sterile plants with pollen from FLP-containing plants,
      viable seeds were produced and the progeny hybrid plants developed normally.
      Molecular analyses revealed that the antisense expression cassette of bcp1 had
      been excised in these plants. These results show for the first time that a site
      specific recombinase can be used to restore fertility in male-sterile plants,
      providing an alternative method for the production of hybrid seeds and plants.

PMID- 10929136
TI  - Leprosy elimination: track record and prospects.

PMID- 10929137
TI  - Mycobacterium leprae--millennium resistant! Leprosy control on the threshold of a
      new era.
AB  - Over the past decades, the conditions of leprosy control implementation have
      changed dramatically. Introduction of multidrug therapy, together with the global
      effort of the World Health Organization to eliminate leprosy as a public health
      problem, had a tremendous impact on leprosy control, particularly by decreasing
      the registered prevalence of the disease. At the beginning of the new millennium,
      leprosy control programmes face several new challenges. These relate not only to
      changes in the prevalence of the disease, but also to changes in the context of
      leprosy control, such as those created by health sector reforms and other disease
      control programmes. This review discusses current knowledge on the epidemiology
      of Mycobacterium leprae and some important aspects of leprosy control. It is
      argued that our understanding is still insufficient and that, so far, no
      consistent evidence exists that the transmission of leprosy has been
      substantially reduced. Sustainable leprosy control, rather than elimination,
      should be our goal for the foreseeable future, which also includes care for
      patients on treatment and for those released from treatment. This, however,
      requires new strategies.

PMID- 10929138
TI  - Viewpoint: leprosy after the year 2000.

PMID- 10929139
TI  - What does a single determination of malaria parasite density mean? A longitudinal
      survey in Mali.
AB  - Temporal variations of blood parasite density were evaluated in a longitudinal
      study of young, asymptomatic men in a village with endemic malaria in Mali (West
      Africa). Our main intention was to challenge the value of a single measure of
      parasite density for the diagnosis of malaria, and to define the level of
      endemicity in any given area. Parasitaemia and body temperature were recorded
      three times a day in the wet season (in 39 subjects on 12 days) and in the dry
      season (in 41 subjects on 13 days). Two thousand nine hundred and fifty seven
      blood smears (98.5% of the expected number) were examined for malaria parasites.
      We often found 100-fold or greater variations in parasite density within a 6-hour
      period during individual follow-up. All infected subjects had frequent negative
      smears. Although fever was most likely to occur in subjects with a maximum
      parasite density exceeding 10000 parasites/mm3 (P = 0.009), there was no clear
      relationship between the timing of these two events. Examples of individual
      profiles for parasite density and fever are presented. These variations (probably
      due to a 'sequestration-release' mechanism, which remains to be elucidated) lead
      us to expect a substantial impact on measurements of endemicity when only a
      single sample is taken. In this study, the percentage of infected individuals
      varied between 28.9% and 57.9% during the dry season and between 27.5% and 70.7%
      during the wet season. The highest rates were observed at midday, and there were
      significant differences between days. Thus, high parasite density sometimes
      associated with fever can no longer be considered as the gold standard in the
      diagnosis of malaria. Other approaches, such as decision-making processes
      involving clinical, biological and ecological variables must be developed,
      especially in highly endemic areas where Plasmodium infection is the rule rather
      than the exception and the possible causes of fever are numerous.

PMID- 10929140
TI  - Prior BCG vaccination improves survival of Gambian patients treated for pulmonary
      tuberculosis.
AB  - The protection provided by BCG against pulmonary tuberculosis ranges from nil to
      over 90%. While BCG protects against the more serious forms of tuberculosis, it
      is not known whether or not it protects patients with pulmonary tuberculosis from
      death. In a study designed to look at the effects of immunotherapy with M. vaccae
      as an adjunct to chemotherapy in 285 adult Gambian patients treated for proven
      pulmonary tuberculosis, we examined the association between the presence or
      absence of a BCG scar and mortality. The data showed that subjects who had a BCG
      scar were significantly younger than those who did not, and were less likely to
      have nutritional oedema. During the course of treatment, none of the 85 patients
      who had a BCG scar died compared to 35 of 200 patients (17.5%) who did not (P <
      0.001). In these Gambian patients with pulmonary tuberculosis, prior vaccination
      with BCG may have provided substantial protection against death. However, there
      is the possibility that this finding is the result of confounding by other
      factors or has arisen from bias. Researchers with similar data need to
      investigate this question as this association, if true, could have major
      implications for BCG vaccination.

PMID- 10929142
TI  - Toxic activities of the plant Jatropha curcas against intermediate snail hosts
      and larvae of schistosomes.
AB  - The aim of studies on plant molluscicides is to complement methods for
      controlling snails acting as intermediate hosts of schistosomes. We report on the
      toxic activity of extracts from Jatropha curcas L. (Euphorbiaceae) against snails
      transmitting Schistosoma mansoni and S. haematobium. We studied different
      extracts' effects on infectious larvae, cercariae and miracidia of S. mansoni.
      Compared to aqueous extract, methanol extract showed the highest toxicity against
      all tested organisms with LC100-values of 25 p.p.m. for cercariae and the snail
      Biomphalaria glabrata and 1 p.p.m. for the snails Bulinus truncatus and B.
      natalensis. Attenuation of cercariae leading to reduced infectivity in mice could
      be achieved in concentrations below those exerting acute toxicity. In view of our
      results and the ongoing exploitation of J. curcas for other purposes, this plant
      could become an affordable and effective component of an integrated approach to
      schistosomiasis control.

PMID- 10929141
TI  - Protection from cholera by adding lime juice to food - results from community and
      laboratory studies in Guinea-Bissau, West Africa.
AB  - Epidemiological studies have shown that food plays an important role in the
      transmission of Vibrio cholerae, and different foods have been incriminated in
      many epidemic outbreaks of cholera. Storing contaminated meals at ambient
      temperatures allows growth of V. cholerae. Some ingredients such as lime juice
      may inhibit the survival of V. cholerae in foods. During an epidemic caused by V.
      cholerae O1 in Guinea-Bissau in 1996, a case control study was conducted in the
      capital Bissau, the main affected region with an attack rate of 7.4%. Cases were
      hospitalized patients and controls were matched for area, gender and age. Lime
      juice in the sauce eaten with rice gave a strong protective effect (odds ratio
      [OR] = 0.31, 95% confidence interval [CI] = 0.17-0.56), and tomato sauce was also
      protective (OR = 0.36, 95% CI = 0.24-0.54). On the other hand, use of a bucket
      for storage of water in the house was associated with increased risk (OR = 4.4,
      CI = 2.21-8.74). Laboratory experiments to elucidate the inhibitory effect of
      different concentrations of lime juice on survival of V. cholerae in meals showed
      that V. cholerae thrives in rice with peanut sauce, but lime juice inhibited its
      growth. Since lime juice is a common ingredient of sauces, its use should be
      further encouraged to prevent foodborne transmission in the household during
      cholera outbreaks.

PMID- 10929143
TI  - Recent urban growth and urinary schistosomiasis in Niamey, Niger.
AB  - A cluster sample survey was conducted in 1998 in 30 schools to assess the effect
      of the growth of Niamey during the last decade on a urinary schistosomiasis urban
      focus described in 1989. Two thousand and forty-two children (11.0 + 0.1 years
      old) had a urine filtration test and answered a behavioural questionnaire. Snail
      populations of the sites used by schoolchildren were followed up in 1999. The
      global prevalence was 15.7% in 1998, as opposed to 23.7% in 1989. The prevalence
      was very low in schools far from the river and higher in those along the Niger
      banks, particularly in villages on the periphery of the urban area. Geographical
      factors were more important than socio-economic ones in explaining the
      distribution of the disease. Only 46% of the children in Niamey reported water
      contact; mainly in the river, rarely in pools and the canal. The infection risk
      was low in pools (RR = 1.6), high in the river (RR = 3.5) and very high in the
      canal (RR = 12.5). Malacological studies confirmed the location of transmission
      sites obtained through parasitological studies and the questionnaire. Sixty-one
      per cent of the children travelled outside Niamey to the hyperendemic surrounding
      areas. However, these movements did not increase their infection level. The
      results are discussed in relation to water contact behaviour and Schistosoma
      haematobium transmission features.

PMID- 10929144
TI  - Inhibition of glutathione synthesis as a chemotherapeutic strategy for
      leishmaniasis.
AB  - This study focuses on the use of buthionine sulphoximine (BSO), a gamma
      glutamylcysteine synthetase inhibitor, on Leishmania donovani growth. The effect
      of BSO on amastigote multiplication within macrophages showed that 5 mM BSO
      decreased infectivity by about 50% and the mean number of amastigotes per 100
      infected macrophages by 21%. The mechanism may be that BSO resulted in enhanced
      nitric oxide (NO) levels within macrophages, probably due to inhibition of GSH
      content since GSH (10 mm) given after BSO treatment led to a decrease in NO
      compared to macrophages treated with BSO alone which were preexposed to the
      Leishmania surface molecule lipophosphoglycan.

PMID- 10929145
TI  - ELISA and western blotting tests in the detection of IgG antibodies to Taenia
      solium metacestodes in serum samples in human neurocysticercosis.
AB  - A comparative study of total saline extract (SE) and cyst vesicular fluid (VF) of
      Taenia solium metacestodes by ELISA and Western blotting assay (WB) tests was
      conducted to detect IgG in sera for diagnosis of human cysticercosis. Sera were
      obtained and analysed by ELISA in 1 : 20 and 1 : 100 dilutions from 208
      individuals: 22 confirmed neurocysticercosis (NC) (group 1), 101 suspected NC
      (group 2), 55 with various intestinal parasitosis (group 3) and 30 healthy
      individuals (group 4). The WB test was carried out on SE and VF extracts with and
      without reducing agent, 2-beta-mercaptoethanol (2-ME) in 20 sera of each group.
      WB using extracts without 2-ME and ELISA at 1 : 100 dilution were compared in 20
      sera from each group; sensitivity and specificity were calculated using samples
      from groups 1, 3 and 4. By ELISA, in the 1 : 100 sera dilution reactivity was
      reduced for both antigens without changes in the sensitivity of the test. By WB,
      antigens treated with 2-ME demonstrated low specificity. For SE and VF antigens,
      the proteins of 24, 39-42, 47-52, 56, 64-68, 126-155 kDa and 18, 24, 26-28, 32
      36, 47-52, 75 kDa, respectively, were considered immunodominant markers, with
      high indices of specificity, suggesting a profile for NC patients. However, as
      the sensitivity was found to be low, it might still not be a definitive test for
      NC when used alone. These data suggest WB as an indicative test to determine
      exposure to T. solium. ELISA and WB together may supply reliable results for the
      diagnosis of human cysticercosis, since appropriate purified antigens are not
      available yet.

PMID- 10929146
TI  - The health and nutritional status of school children in two rural communities in
      Sri Lanka.
AB  - There is growing evidence of considerable burden of morbidity and mortality due
      to infectious diseases and undernutrition in school children. This study
      describes the nutritional status and parasitic infections of school children in
      two areas of rural Sri Lanka. All children in four primary schools in the
      Moneragala district of Sri Lanka were included in the study. The height and
      weight of children were measured and anthropometric indices calculated. Stool and
      blood samples were examined for evidence of intestinal helminthiasis, malaria and
      anaemia. A greater proportion of boys than girls were underweight, wasted and
      stunted. Over 80% of the children were anaemic but did not apparently have iron
      deficiency anaemia according to their blood picture. The prevalence of parasitic
      infections such as hookworm and Plasmodium spp that may contribute to anaemia was
      low.

PMID- 10929147
TI  - Microsporidia and Candida spores: their discrimination by Calcofluor, trichrome
      blue and methylene-blue combination staining.
AB  - Faeces of immunocompromised patients are often contaminated with the chitin
      containing spores of microsporidia and Candida, which exclude the use of the
      chitin-specific fluorescent brightener Calcofluor white M2R for the
      identification of microsporidian spores. We developed a combination staining of
      Calcofluor white M2R with modified trichrome-blue staining and subsequent
      methylene-blue incubation which permits discrimination between these two types of
      spores. As a basis for diagnosis, a difference in the fluorescence pattern (365
      440 nm) is combined with a difference in the light microscopic staining pattern.
      Under fluorescence conditions microsporidia spores have a spotted, brilliant
      white Calcofluor fluorescence and can easily be identified, while Candida spores
      show a reddish purple colour. Under the light microscope microsporidian spores
      show a light red colour with nonstained vacuole spots or strips in contrast to
      the yeast spores with their red-brown colour. This combination technique offers a
      highly specific means for the diagnosis of microsporidia spores in faeces.

PMID- 10929148
TI  - In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi,
      Kenya and Kigoma, Tanzania.
AB  - We conducted two randomized clinical trials to determine the in vivo efficacy of
      amodiaquine and sulfadoxine/pyrimethamine in treating Plasmodium falciparum
      malaria. Seventy-five patients under the age of 10 years in Kibwezi, Kenya, and
      171 patients in Kigoma, Tanzania, were enrolled for treatment. Due to loss of
      eight patients in Kibwezi and 37 in Kigoma to follow-up, we used best and worst
      case scenarios for the parasitological response. The in vivo sensitivity of
      Plasmodium falciparum to amodiaquine was 75% (no loss to follow-up) in Kibwezi
      and ranged from 85% in the best to 65% in the worst case scenario in Kigoma. The
      sensitivity to sulfadoxine/pyrimethamine was 70% to 88% in Kibwezi and 65% to 89%
      in Kigoma. R1 resistance to amodiaquine was 22% in Kibwezi and varied from 6% in
      the best to 26% for the worst case scenario in Kigoma. The R1 resistance to
      sulfadoxine/pyrimethamine was 5% to 23% in Kibwezi and 2% to 26% in Kigoma. R2
      resistance was 3% for amodiaquine and 7% for sulfadoxine/pyrimethamine in Kibwezi
      and 9% in Kigoma for each treatment group. There was no statistically significant
      difference between treatment groups at either study site, except for a slight
      difference in R1 resistance in the best case scenario, Kibwezi, in favour of S/P.
      Although both amodiaquine and sulfadoxine/pyrimethamine resistance seems to be
      increasing, these antimalarials are still effective in parasite clearance.

PMID- 10929149
TI  - Stool microscopy.

PMID- 10929150
TI  - Modification of pathological type A as worksite stress management and disease
      prevention intervention.
AB  - The importance of helping an employee to better cope with occupational stress as
      the aim of stress management interventions is presented. It particularly concerns
      the employees who have the poorest temperamental and personality potential for
      effective coping and should be the target of primary stress intervention and
      prevention. According to evidence, Type A workers are at risk of occupational
      stress and disease, especially when some personality features of Type A are
      accompanied by high reactivity. The concept of pathological Type A is introduced.
      The already existing programs of modifying Type A and the framework of a program
      based on the elements that have been established to be the most therapeutic for
      pathological Type A are presented.

PMID- 10929151
TI  - Evaluation of health status and quality of life after bariatric surgery:
      comparison of standard Roux-en-Y gastric bypass, vertical banded gastroplasty and
      laparoscopic adjustable silicone gastric banding.
AB  - BACKGROUND: This study is a trial to compare the effects and outcomes of three
      different bariatric procedures performed in two centers. Standard Roux-en-Y
      gastric bypass was performed by Dr. Norman Samuels in Fort Lauderdale (Florida);
      vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding
      were done in Hallein (Salzburg) by Dr. Emanuel Hell and Dr. Karl Miller. METHODS:
      In a prospective comparative study 30 matched patients from each group were
      followed to assess post-operative improvement in health status and quality of
      life, to compare the three different techniques. The Bariatric Analysis and
      Reporting Outcome System (BAROS) as described by Oria and Moorehead has been used
      for evaluation. RESULTS: The observation time was at least 3 years (3 to 8 years)
      in each individual case. A significant increase in quality of life and health
      status in 75% of the surgically-treated patients was observed when compared with
      a non-operated control group of morbidly obese patients. CONCLUSIONS: By
      utilizing BAROS it has been found possible to compare the results of different
      procedures done by different surgeons with different techniques, utilizing
      patients from different cultures and with different languages. The results of
      this comparative study favor the standard gastric bypass for the treatment of
      morbid obesity. This operation is superior to purely gastric restrictive
      procedures in weight loss and improvement of quality of life.

PMID- 10929152
TI  - Continuous spinal anesthesia/analgesia for perioperative management of morbidly
      obese patients undergoing laparotomy for gastroplastic surgery.
AB  - BACKGROUND: The authors determined prospectively the safety of continuous spinal
      anesthesia combined with general anesthesia and the efficacy of postoperative
      pain relief with continuous spinal analgesia for morbidly obese patients
      undergoing vertical banded gastroplasty. METHODS: 27 patients (13 men, 14 women)
      with a mean body mass index (BMI) of 50.4 +/- 7.8 and several co-morbidities were
      studied. All patients were anesthetized with the same anesthetic regimen, which
      included midazolam, fentanyl, propofol, muscle relaxants, nitrous oxide,
      isoflurane and intrathecal bupivacaine. Postoperative pain relief was provided
      for 5 days and all patients received the same regimen, which included intrathecal
      bupivacaine, fentanyl and intravenous tenoxicam. The intrathecal analgesic
      regimen was administered continuously through a pump which had the facility of
      providing bolus doses when requested in predetermined lockout intervals. Intra
      operative monitoring included hemodynamic and respiratory parameters. Additional
      postoperative monitoring included respiratory rate, degree of sedation, sensory
      level of anesthesia, motor response and intensity of pain. RESULTS:
      Intraoperative anesthetic technique was safe and provided satisfactory results in
      the immediate postoperative period. Furthermore, the postoperative analgesia
      regimen provided effective analgesia in all patients. The mean doses of fentanyl
      and bupivacaine infused intrathecally for the first 24 postoperative hours were
      14.1 +/- 2.0 microg.h(1) and 0.7 +/- 0.1 mg.h(1) respectively, while the
      requirements of analgesia decreased progressively with time. The technique
      provided effective analgesia with low pain scores, which was reflected by ease in
      mobilizing and performing physical exercises with the physiotherapist. Only minor
      complications related to anesthesia and analgesia were encountered. CONCLUSION:
      To our knowledge, this technique of anesthesia and postoperative analgesia has
      not been described before in morbidly obese patients. This regimen merits further
      controlled trials to establish its place in the perioperative management of
      morbidly obese patients.

PMID- 10929153
TI  - A technique of stapled gastrojejunostomy for open gastric bypass results in
      increased wound complication-rate.
AB  - BACKGROUND: Gastric bypass may be facilitated by a stapled gastrojejunostomy.
      This study compared two different techniques for performing this critical
      anastomosis in open surgery. METHODS: 67 consecutive patients were
      retrospectively studied for weight loss, hospital length of stay, anastomotic
      stricture, wound complication, and incisional hernia. 49 patients had a two layer
      hand-sutured gastrojejunostomy over a 34 Fr bougie via a laparotomy (sutured). 18
      patients had a stapled gastrojejunostomy using the technique of Wittgrove and
      Clark via a laparotomy (stapled). All patients received prophylactic intravenous
      antibiotics preoperatively. RESULTS: Initial BMI, % of excess weight lost at 6
      weeks and 6 months, and hospital length of stay were not statistically different
      between the groups. However, the rate of wound complication and incisional hernia
      rate were significantly higher in the stapled group when compared to the sutured
      group (p< 0.01). CONCLUSIONS: Based on these data we suggest that the technique
      of Wittgrove and Clark for performing the gastrojejunostomy should not be used in
      open gastric bypass as it results in increased rates of wound complication and
      incisional hernia.

PMID- 10929154
TI  - Laparoscopic gastric bypass, Roux-en-Y- 500 patients: technique and results, with
      3-60 month follow-up.
AB  - BACKGROUND: The authors have performed the laparoscopic gastric bypass since 1993
      and perform about one-half of bariatric cases laparoscopically. Since our initial
      report, several groups throughout the world have preformed the gastric bypass
      laparoscopically, with various modifications. METHOD: Prospectively, we followed
      and recorded the results of our laparoscopic patients. A detailed pre- and post
      operative analysis of the patient's co-morbidities is performed as well as
      complete weight and laboratory data evaluation. RESULTS: With > 80% follow-up, we
      found an excess weight loss of about 80% by the first year. This degree of loss
      is well sustained. Over 95% of the significant pre-operative co-morbidities are
      controlled. CONCLUSION: The laparoscopic gastric bypass has been refined over 5
      years of use. Though we have not changed the basic operation as we originally
      described, others have modified the various anastomotic techniques. The weight
      loss results are very good to excellent, with patients now out to "long-term"
      follow-up. Resolution of the co-morbidities is documented. The operation has an
      adequate track record to show effectiveness, and training programs should be
      established to maximize safety.

PMID- 10929155
TI  - An alternative technique for creating the gastrojejunostomy in laparoscopic Roux
      en-Y gastric bypass: experience with 28 consecutive patients.
AB  - BACKGROUND: This study illustrates our experience in laparoscopic Roux-en-Y
      gastric bypass (LRYGBP) using a new technique for creating the gastro
      jejunostomy. METHODS: Between April and November 1999, 28 patients underwent
      LRYGBP. In the first 10 patients the transoral route with endoscopic guidance was
      utilized for placement of the anvil in the gastric pouch. A new totally intra
      peritoneal approach was utilized in the next 18 patients, avoiding the trans-oral
      route. RESULTS: There were 23 women and 5 men with an average age of 36 years
      (range 24-51). The mean BMI was 47, with range 41-64. Of the patients, 82% had
      one or more associated co-morbid conditions (hypertension, diabetes, sleep apnea,
      arthritis). Average operative time in the first 10 patients using the trans-oral
      route with endoscopic guidance was 340 minutes (range 240-390 min). The next 18
      patients underwent totally intra-peritoneal anvil placement with a 240-minute
      average operating time (range 150-310 min). There were no open conversions or
      mortalities. There were 4 complications, including 2 wound infections, one
      urinary tract infection, and one intra-abdominal abscess. The two wound
      infections occurred in the first 10 patients that underwent trans-oral
      introduction of the anvil. CONCLUSIONS: LRYGBP was a safe and feasible operation.
      We believe that our technique is easily reproducible, avoiding the trans-oral
      route for introducing the anvil. This technique may also decrease operative time
      and possibly the incidence of wound infections, although we are still in the
      learning curve and final conclusions cannot be made.

PMID- 10929156
TI  - Gastric emptying rate measurement after vertical banded gastroplasty.
AB  - BACKGROUND: In vertical banded gastroplasty (VBG), a small proximal gastric pouch
      is created, which is believed to fill rapidly and to empty slowly. METHODS: In 13
      patients who underwent VBG, gastric emptying rate was measured. A radiolabelled
      solid test meal was used before and 2 weeks after operation. From a region of
      interest above the whole stomach, the proximal pouch and the distal stomach, half
      emptying time as well as retention percentage were derived. RESULTS: All patients
      experienced early satiety and gastric fullness after ingestion of a small test
      meal. The proximal pouch emptied rapidly. The evacuation of the test meal from
      the whole gastric region as well as the distal stomach were not altered
      significantly by the operation. CONCLUSION: VBG is a safe operation which reduced
      weight significantly. Early satiety, however, induced by this technique, cannot
      be explained alone by slow emptying of the proximal pouch. The nature of the
      outlet of the pouch as well as the behavior of its wall must be considered.

PMID- 10929157
TI  - Silastic ring vertical gastroplasty- long-term results and complications.
AB  - BACKGROUND: Silicone ring vertical gastroplasty (SRVG) in some reports is
      associated with significant morbidity and a tendency to regain weight in the late
      postoperative period. The present study aims to evaluate our long-term results,
      along with early and late postoperative complications. METHODS: The early and
      late postoperative complications of 300 patients undergoing SRVG and followed for
      an average of 3.2 years, were reviewed retrospectively. The pre- and post
      operative weight and body mass index (BMI) were recorded in a subgroup of 131
      patients with an average follow-up of 5.2 years. RESULTS: Early postoperative
      complications occurred in 99 patients (33.1%), with mortality of one patient
      (0.3%). Vomiting was the most common late complication, occurring in 49.3%. Re
      operation was performed in 19.7% of the patients, mostly for the repair of
      postoperative ventral hernia. Long-term results following SRVG showed a decrease
      in weight from 131 +/- 25 kg to 94 +/- 23.2 kg, and BMI decreased from 46.1 +/-
      8.1 kg /m(2) to 32.9 +/- 7.4 kg/m(2). Excess body weight loss was 58.5 +/- 39.8%.
      CONCLUSIONS: Most patients (76%) reported their satisfaction following SRVG. Long
      term results revealed a significant and sustained weight loss, mild complications
      and low mortality rate.

PMID- 10929158
TI  - Bariatric surgery in some "Central and East-European (former Eastern bloc)"
      countries- current status and prediction for the next millennium.
AB  - BACKGROUND: Obesity is increasing globally, including in the formerly "Eastern
      Bloc" countries. METHODS: A survey was made of obesity and bariatric surgery.
      RESULTS: In the 8 East and Central European countries studied, with total
      population 300 million, roughly 43% of the population was overweight (BMI 25-30),
      23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40).
      From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery.
      CONCLUSION: Most countries were found to provide inadequate treatment for
      obesity. The majority of the morbidly obese are not treated effectively. However,
      health-care awareness of obesity and bariatric surgeons are slowly increasing.

PMID- 10929159
TI  - Injection port complications after gastric banding: incidence, management and
      prevention.
AB  - BACKGROUND: Laparoscopic adjustable gastric banding is advocated as a minimal
      invasive procedure with a low risk profile and high efficacy in the treatment of
      morbid obesity. Nevertheless, injection port complications are occasionally
      reported. The aim of this study was to assess port disconnections and port
      dislodgement with respect to two different implantation techniques. METHODS:
      Between January 1996 and October 1999 230 patients underwent laparoscopic gastric
      banding with the Swedish Adjustable Gastric Band (SAGB). In group 1 (118
      patients), the injection port was implanted onto the sterno-xiphoid union. In
      group 2 (112 patients), an additional incision was made to suture the port onto
      the fascia of the lower third of the sternum. RESULTS: There is a significant
      reduction in port disconnection between group 1 (9.3 %) and group 2 (0 %). Port
      dislodgment was observed in one patient in each group. Reoperation was performed
      under local anesthesia in 11 patients, and general anesthesia was used for
      laparoscopic tube salvage in two patients. After reconnection, two patients
      experienced port infection. CONCLUSION: Correct implantation technique of the
      injection port of the SAGB onto the fascia of the lower third of the sternum
      reduces the risk for port complications. Technical notes are discussed.

PMID- 10929160
TI  - Laparotomic vs laparoscopic lap-band: 4-year results with early and intermediate
      complications.
AB  - BACKGROUND: Adjustable banding is safe, low invasive, and effective for losing
      weight. METHODS: 69 patients underwent this procedure by laparotomy or
      laparoscopy. RESULTS: Patients operated by laparotomy lost more weight than those
      operated by laparoscopy, but in 4 patients we were forced to re-operate in order
      to remove the band (3 pouch dilatations and 1 stomach slippage), and in 9
      patients a ventral hernia appeared (5 patients repaired). In the laparoscopic
      cases there were 4 intra-operative gastric perforations, but all were repaired
      and the band placed at the same time (3 conversions to open), causing an
      increased post-operative hospital stay. There was a lower limb deep venous
      thromboembolism, which was followed by fatal pulmonary embolism (although the
      patient had been given heparin and had been treated with elastocompression and
      mobilization 2 hours after surgery). The band eroded in one patient. Weight
      losses in these morbidly obese patients were satisfactory at 2 years and
      maintained beyond 3 years. CONCLUSION: Laparoscopic adjustable banding is an
      efficient, generally safe procedure.

PMID- 10929161
TI  - Thirty months experience with laparoscopic adjustable gastric banding.
AB  - INTRODUCTION: Since June 1996 we performed laparoscopic adjustable silicone
      gastric banding (LASGB), because of low invasivity, absence of malabsorption,
      reversibility, and postoperative regulation. MATERIALS AND METHODS: Criteria
      included body mass index (BMI) >40 or >35 with serious obesity-related
      conditions. 154 patients underwent LASGB. BMI ranged from 35 to 65.7 (mean 43.7+/
      6.2). RESULTS: The laparoscopic procedure was successfully completed in 150
      patients (97.4%). One patient was converted to the laparotomic procedure because
      of hepatomegaly; 4 patients had to be converted for gastric laceration during the
      laparoscopic approach. In one of these patients, the band was removed 7 days
      later for sepsis, followed by an uneventful postoperative course. The mean length
      of postoperative hospitalization was 2.3+/-0.9 days. Per cent of excess weight
      loss was 42.5+/-22.4 after 1 year. CONCLUSIONS: LASGB was feasible and effective.

PMID- 10929162
TI  - Bariatric surgery: early results with a multidisciplinary team.
AB  - BACKGROUND: Bariatric surgery depends on complete preoperative study of morbid
      obesity, in order to obtain the treatment of choice. A multidisciplinary group
      was founded in 1998 at the University of Siena. METHODS: During 1998, 16
      patients, with median weight 121.8 +/- 31 kg and median body mass index (BMI) 43
      +/- 6, underwent bariatric surgery. A multidisciplinary assessment was used in
      order to evaluate psychological status, food intake problems and patient
      compliance, and hemodynamic, respiratory, metabolic and arthritic functions. 13
      patients were submitted to laparoscopic surgery: in 11 adjustable gastric banding
      was performed and 2 were submitted to a vertical gastroplasty plus adjustable
      gastric banding. Three patients were operated via traditional laparotomy, due to
      previous abdominal surgery in 2 cases (submitted to an adjustable gastric
      banding) and one woman was submitted to a bilio-intestinal bypass according to
      the Hallberg technique, for her psychiatric troubles and coexisting systolic
      hypertension and uncontrolled diabetes. Monthly follow-up for each patient
      continues after 6 months. RESULTS: No morbidity or mortality has occurred. The
      median weight loss at three months, was 19.5 kg. Two cases required injection of
      1 ml more of fluid into the port, respectively at 4 and 9 months. Fifteen days
      after surgery, seven patients (46%) had vomiting episodes, due to rapid food
      intake. All patients have shown an improvement of their comorbidities after
      surgery. CONCLUSION: Early results via the multidisciplinary team and
      laparoscopic banding have been satisfactory thus far.

PMID- 10929164
TI  - Effect of a preoperative intervention on preoperative and postoperative outcomes
      in low-risk patients awaiting elective coronary artery bypass graft surgery. A
      randomized, controlled trial.
AB  - BACKGROUND: In publicly funded health care systems, a waiting period for such
      services as coronary artery bypass graft surgery (CABG) is common. The
      possibility of using the waiting period to improve patient outcomes should be
      investigated. OBJECTIVE: To examine the effect of a multidimensional preoperative
      intervention on presurgery and postsurgery outcomes in low-risk patients awaiting
      elective CABG. DESIGN: Randomized, controlled trial. SETTING: A regional
      cardiovascular surgery center in a tertiary care hospital, southwestern Ontario,
      Canada. PATIENTS: 249 patients on a waiting list for elective CABG whose
      surgeries were scheduled for a minimum of 10 weeks from the time of study
      recruitment. INTERVENTION: During the waiting period, the treatment group
      received exercise training twice per week, education and reinforcement, and
      monthly nurse-initiated telephone calls. After surgery, participation in a
      cardiac rehabilitation program was offered to all patients. MEASUREMENTS:
      Postoperative length of stay was the primary outcome. Secondary outcomes were
      exercise performance, general health-related quality of life, social support,
      anxiety, and utilization of health care services. RESULTS: Length of stay
      differed significantly between groups. Patients who received the preoperative
      intervention spent 1 less day [95% CI, 0.0 to 1.0 day] in the hospital overall (P
      = 0.002) and less time in the intensive care unit (median, 2.1 hours [CI, -1.2 to
      16 hours]; P = 0.001). During the waiting period, patients in the intervention
      group had a better quality of life than controls. Improved quality of life
      continued up to 6 months after surgery. Mortality rates did not differ.
      CONCLUSION: The waiting period for elective procedures, such as CABG, may be used
      to enhance in-hospital and early-phase recovery, improving patients' functional
      abilities and quality of life while reducing their hospital stay.

PMID- 10929163
TI  - Duration of symptoms and plasma cytokine levels in patients with the common cold
      treated with zinc acetate. A randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Adults and children in the United States get two to six colds per
      year. Evidence that zinc is effective therapy for colds is inconsistent.
      OBJECTIVE: To test the efficacy of zinc acetate lozenges in reducing the duration
      of symptoms of the common cold. DESIGN: Randomized, double-blind, placebo
      controlled trial. SETTING: Detroit Medical Center, Detroit, Michigan. PATIENTS:
      50 ambulatory volunteers recruited within 24 hours of developing symptoms of the
      common cold. INTERVENTION: Participants took one lozenge containing 12.8 mg of
      zinc acetate or placebo every 2 to 3 hours while awake as long as they had cold
      symptoms. MEASUREMENTS: Subjective symptom scores for sore throat, nasal
      discharge, nasal congestion, sneezing, cough, scratchy throat, hoarseness, muscle
      ache, fever, and headache were recorded daily for 12 days. Plasma zinc and
      proinflammatory cytokine levels were measured on day 1 and after participants
      were well. RESULTS: Forty-eight participants completed the study (25 in the zinc
      group and 23 in the placebo group). Compared with the placebo group, the zinc
      group had shorter mean overall duration of cold symptoms (4.5 vs. 8.1 days),
      cough (3.1 [95% CI, 2.1 to 4.1] vs. 6.3 [CI, 4.9 to 7.7] days), and nasal
      discharge (4.1 [CI, 3.3 to 4.9] vs. 5.8 [CI, 4.3 to 7.3] days) and decreased
      total severity scores for all symptoms (P < 0.002, test for treatment x time
      interaction). Mean changes in soluble interleukin-1 receptor antagonist level
      differed nonsignificantly between the zinc group and the placebo group
      (difference between changes, -89.4 pg/mL [CI, -243.6 to -64.8 pg/mL]).
      CONCLUSION: Administration of zinc lozenges was associated with reduced duration
      and severity of cold symptoms, especially cough. Improvement in clinical symptoms
      with zinc treatment may be related to a decrease in proinflammatory cytokine
      levels; however, in this study, the observed differences between changes in
      cytokine levels in zinc and placebo recipients were not significant.

PMID- 10929165
TI  - MRI.

PMID- 10929167
TI  - When Did I Know I Loved Her?

PMID- 10929166
TI  - Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes.
AB  - BACKGROUND: Troglitazone promotes adipocyte differentiation in vitro and
      increases insulin sensitivity in vivo. Therefore, troglitazone may have
      therapeutic benefit in lipoatrophic diabetes. OBJECTIVE: To determine whether
      troglitazone ameliorates hyperglycemia and hypertriglyceridemia or increases fat
      mass in lipoatrophic patients. DESIGN: Open-labeled prospective study. SETTING:
      United States and Canada. PATIENTS: 20 patients with various syndromes associated
      with lipoatrophy or lipodystrophy. INTERVENTION: 6 months of therapy with
      troglitazone, 200 to 600 mg/d. MEASUREMENTS: Levels of hemoglobin A1c
      triglycerides, free fatty acids, and insulin; respiratory quotient; percentage of
      body fat; liver volume; and regional fat mass. RESULTS: In the 13 patients with
      diabetes who completed 6 months of troglitazone therapy, hemoglobin A1c levels
      decreased by a mean of 2.8% (95% CI, 1.9% to 3.7%; P < 0.001). In all 19 study
      patients, fasting triglyceride levels decreased by 2.6 mmol/L (230 mg/dL) (CI,
      0.7 to 4.5 mmol/L [62 to 398 mg/dL]; P = 0.019) and free fatty acid levels
      decreased by 325 micromol/L (CI, 135 to 515 micromol/L; P = 0.035). The
      respiratory quotient decreased by a mean of 0.12 (CI, 0.08 to 0.16; P < 0.001),
      suggesting that troglitazone promoted oxidation of fat. Body fat increased by a
      mean of 2.4 percentage points (CI, 1.3 to 4.5 percentage points; P = 0.044).
      Magnetic resonance imaging showed an increase in subcutaneous adipose tissue but
      not in visceral fat. In one patient, the serum alanine aminotransferase level
      increased eightfold during the 10th months of troglitazone treatment but
      normalized 3 months after discontinuation of treatment Liver biopsy revealed an
      eosinophilic infiltrate, suggesting hypersensitivity reaction as a cause of
      hepatotoxicity. CONCLUSION: Troglitazone therapy improved metabolic control and
      increased body fat in patients with lipoatrophic diabetes. The substantial
      benefits of troglitazone must be balanced against the risk for hepatotoxicity,
      which can occur relatively late in the treatment course.

PMID- 10929168
TI  - Anti-CD20 chimeric monoclonal antibody treatment of refractory immune-mediated
      thrombocytopenia in a patient with chronic graft-versus-host disease.
AB  - BACKGROUND: Autoimmune thrombocytopenia in chronic graft-versus-host disease may
      represent an instance of B-cell dysregulation leading to clinical disease.
      OBJECTIVE: To attempt to treat refractory immune-mediated thrombocytopenia in a
      patient with chronic graft-versus-host disease by using anti-CD20 chimeric
      monoclonal antibody. DESIGN: Case report. SETTING: Academic medical center.
      PATIENT: A patient with chronic graft-versus-host disease after allogeneic
      peripheral blood stem-cell transplantation who had severe refractory immune
      mediated thrombocytopenia. INTERVENTION: Weekly infusion of rituximab, 375 mg/m2,
      for 4 weeks. MEASUREMENTS: Platelet count, CD3+ cell count, and CD19+ cell count.
      RESULTS: Rituximab therapy resulted in marked depletion of B cells in the
      peripheral blood and decreased levels of platelet-associated antibody. The
      increase in platelet count persisted despite tapering and discontinuation of
      immunosuppressive therapy for chronic graft-versus-host disease. CONCLUSION: The
      efficacy of rituximab for the treatment of immune-mediated thrombocytopenia
      suggests that this drug may have activity in other autoimmune diseases or chronic
      graft-versus-host disease.

PMID- 10929169
TI  - Effect of antiretroviral therapy on HIV shedding in semen.
AB  - BACKGROUND: The effect of antiretroviral therapy on seminal HIV shedding in the
      community remains unknown. OBJECTIVE: To evaluate the effect of antiretroviral
      therapy on HIV shedding in semen. DESIGN: Prospective cohort study. SETTING:
      University hospital in Rio de Janeiro, Brazil. PATIENTS: 93 HIV-infected men.
      INTERVENTION: Antiretroviral therapy as prescribed by each patient's physician.
      MEASUREMENT: HIV RNA in semen and blood plasma before and after introduction of
      therapy. RESULTS: At baseline, HIV RNA was detected in 69 semen samples (74%) and
      89 blood samples (96%). Six months after introduction of therapy, HIV RNA was
      detected in 29 semen samples (33%) and 33 blood samples (38%). The mean reduction
      in levels of HIV RNA in semen at 6 months was 1.65 log10 units. CONCLUSIONS:
      Antiretroviral therapy reduces shedding of HIV in semen, which probably in tum
      reduces HIV transmissibility. However, a substantial proportion of patients may
      still be infectious and may have drug-resistant strains of the virus.

PMID- 10929170
TI  - Update in infectious diseases.

PMID- 10929171
TI  - The department of internal medicine: hub of the academic health center response
      to the aging imperative.
AB  - In the 21st century, geriatrics will increasingly dominate U.S. health care as
      the median age of the population progressively increases. Academic departments of
      geriatrics have been created in nations that have already experienced this shift.
      As an alternative strategy that builds on traditional strengths of academic
      medicine in the United States, departments of internal medicine should lead a
      multidepartmental, pan-institutional response to the aging imperative.
      Recognition of gerontology and geriatric medicine as central to the missions of
      internal medicine in clinical care, education, and research must be increased. In
      the process, academic departments of internal medicine will develop a high level
      of geriatric expertise and will launch many programs that address this challenge.
      Successful development of geriatric programs will serve as a catalyst to
      strengthen the integration among and between generalists and subspecialists. This
      will entail developing optimal sites and systems of geriatric care--at different
      levels of care and over time--that can enhance the geriatric education of medical
      students, residents, fellows, and practicing physicians. The study of aging and
      geriatric health care will also become an integral part of departmental research,
      in its subspecialty divisions as well as its divisions of general internal
      medicine and geriatrics. This strategy is urgently recommended as both a
      challenge and an opportunity for all departments of internal medicine.

PMID- 10929172
TI  - In defense of a department of geriatrics.
AB  - Departmental status for geriatrics offers many advantages, all of which are
      related to strengthening academic and clinical programs in aging. The training
      programs and the content of medical school curriculum in geriatrics remain
      inadequate under the current structures. A department of geriatrics can provide a
      stronger faculty base and allow effective interaction with other departments
      (including but not limited to internal medicine) that need geriatric training. A
      department of geriatrics also focuses on a model of care that involves working
      closely with other disciplines, such as nursing and social work. This
      interdisciplinary model helps expert providers work efficiently throughout the
      spectrum of care, strengthening continuity. The department can include other
      medical specialists, such as family practitioners, psychiatrists, and
      physiatrists, who work with caregivers and patients throughout a course of
      treatment to manage chronic illness and help maintain and enhance function and
      independence as long as possible. Comprehensive care and proper care management
      also substantially benefit institutions by expanding the patient population,
      reducing length of stay, and avoiding unnecessary hospitalization of older
      patients through effective discharge planning and transitional care. This
      requires strong relationships with long-term care providers, a characteristic
      strength of geriatricians. Although not all research in aging needs to be housed
      in a department of geriatric medicine, the presence of a critical mass of basic
      and clinical researchers creates an environment that can stimulate new
      initiatives and attract external funding. Additional research bridging basic
      translational and clinical phases relevant to the elderly population is best
      encouraged by maintaining relationships with other basic science and clinical
      departments.

PMID- 10929173
TI  - Lessons learned from attempts to establish the blind in placebo-controlled trials
      of zinc for the common cold.

PMID- 10929174
TI  - Lipoatrophy, lipodystrophy, and insulin resistance.

PMID- 10929175
TI  - Economic sanctions and embargoes.

PMID- 10929176
TI  - Economic sanctions and embargoes.

PMID- 10929177
TI  - Economic sanctions and embargoes.

PMID- 10929178
TI  - Economic sanctions and embargoes.

PMID- 10929180
TI  - Economic sanctions and embargoes.

PMID- 10929179
TI  - Economic sanctions and embargoes.

PMID- 10929181
TI  - Economic sanctions and embargoes.

PMID- 10929182
TI  - Economic sanctions and embargoes.

PMID- 10929183
TI  - Economic sanctions and embargoes.

PMID- 10929185
TI  - Radiofrequency ablation of metastatic lesions in adrenocortical cancer.

PMID- 10929184
TI  - Histologic improvement of fibrosis in patients with hepatitis C and sustained
      response to interferon therapy.

PMID- 10929186
TI  - The pet separation syndrome.

PMID- 10929187
TI  - Laryngopharyngeal examination: an important but not-so-new role of upper
      gastrointestinal endoscopy.

PMID- 10929188
TI  - Tobacco awareness curricula in medical schools.

PMID- 10929189
TI  - Glutaraldehyde colitis: a complication of screening flexible sigmoidoscopy in the
      primary care setting.

PMID- 10929190
TI  - Liver Disease: Diagnosis and Management.

PMID- 10929191
TI  - Emerging Infections 3.

PMID- 10929192
TI  - The effect of clinical practice guidelines on variations in care.

PMID- 10929193
TI  - Vitamin D.

PMID- 10929194
TI  - Gene conversion of ribosomal DNA in Nicotiana tabacum is associated with
      undermethylated, decondensed and probably active gene units.
AB  - We examined the structure, intranuclear distribution and activity of ribosomal
      DNA (rDNA) in Nicotiana sylvestris (2n = 2x = 24) and N. tomentosiformis (2n = 2x
      = 24) and compared these with patterns in N. tabacum (tobacco, 2n = 4x = 48). We
      also examined a long-established N. tabacum culture, TBY-2. Nicotiana tabacum is
      an allotetraploid thought to be derived from ancestors of N. sylvestris (S-genome
      donor) and N. tomentosiformis (T-genome donor). Nicotiana sylvestris has three
      rDNA loci, one locus each on chromosomes 10, 11, and 12. In root-tip meristematic
      interphase cells, the site on chromosome 12 remains condensed and inactive, while
      the sites on chromosomes 10 and 11 show activity at the proximal end of the locus
      only. Nicotiana tomentosiformis has one major locus on chromosome 3 showing
      activity and a minor, inactive locus on chromosome 11. In N. tabacum cv. 095-55,
      there are four rDNA loci on T3, S10, S11/t and S12 (S11/t carries a small T
      genome translocation). The locus on S12 remains condensed and inactive in root
      tip meristematic cells while the others show activity, including decondensation
      at interphase and secondary constrictions at metaphase. Nicotiana tabacum DNA
      digested with methylcytosine-sensitive enzymes revealed a hybridisation pattern
      for rDNA that resembled that of N. tomentosiformis and not N. sylvestris. The
      data indicate that active, undermethylated genes are of the N. tomentosiformis
      type. Since S-genome chromosomes of N. tabacum show rDNA expression, the result
      indicates rDNA gene conversion of the active rDNA units on these chromosomes.
      Gene conversion in N. tabacum is consistent with the results of previous work.
      However, using primers specific for the S-genome rDNA intergenic sequences (IGS)
      in the polymerase chain reaction (PCR) show that rDNA gene conversion has not
      gone to completion in N. tabacum. Furthermore, using methylation-insensitive
      restriction enzymes we demonstrate that about 8% of the rDNA units remain of the
      N. sylvestris type (from ca. 75% based on the sum of the rDNA copy numbers in the
      parents). Since the active genes are likely to be of an N. tomentosiformis type,
      the N. sylvestris type units are presumably contained within inactive loci (i.e.
      on chromosome S12). Nicotiana sylvestris has approximately three times as much
      rDNA as the other two species, resulting in much condensed rDNA at interphase.
      This species also has three classes of IGS, indicating gene conversion has not
      homogenised repeat length in this species. The results suggest that methylation
      and/or DNA condensation has reduced or prevented gene conversion from occurring
      at inactive genes at rDNA loci. Alternatively, active undermethylated units may
      be vulnerable to gene conversion, perhaps because they are decondensed and
      located in close proximity within the nucleolus at interphase. In TBY-2,
      restriction enzymes showed hybridisation patterns that were similar to, but
      different from, those of N. tabacum. In addition, TBY-2 has elevated rDNA copy
      number and variable numbers of rDNA loci, all indicating rDNA evolution in
      culture.

PMID- 10929195
TI  - Amplification of a long terminal repeat-like element on the Y chromosome of the
      platyfish, Xiphophorus maculatus.
AB  - The platyfish (Xiphophorus maculatus), in which sex chromosomes are evident from
      stable and predictable inheritance of sex, is one of the best-studied lower
      vertebrates with respect to sex determination. In order to identify the
      structural equivalent for this in the karyotype, which does not contain
      heteromorphic pairs of chromosomes, two sex-linked molecular probes were used for
      fluorescent in situ hybridization analysis. One probe, derived from the melanoma
      oncogene locus ONC-Xmrk, stained both the X and the Y chromosome. This
      cytogenetic analysis mapped the sex-determining locus to the subtelomeric region
      of a medium-sized telocentric chromosome. Another probe, a repetitive element
      (XIR), specifically labeled the Y chromosome in metaphase spreads and in
      interphase nuclei. The sex chromosomes of X. maculatus can be considered to be at
      an early stage of evolution of gonosomes. Expansion of the XIR repeat is
      obviously one of the earliest of the molecular events that lead to divergence of
      the Y chromosome and recombinational isolation of the sex-determining locus.

PMID- 10929196
TI  - Unusual chromosome architecture and behaviour at an HSR.
AB  - Amplification of sequences within mammalian chromosomes is often accompanied by
      the formation of homogeneously staining regions (HSRs). The arrangement of DNA
      sequences within such amplicons has been investigated, but little is known about
      the chromosome structure or behaviour of these unusual regions. We have analysed
      the metaphase chromosome structure of the dihydrofolate reductase (DHFR) amplicon
      of CHOC400 cells. The chromatin in this region contains hyperacetylated
      nucleosomes yet, at the same time, appears to be densely packed like
      heterochromatin. The region does not bind heterochromatin proteins. We show that
      the dense packing of the region is restricted to DNA located close to the
      chromosome core/scaffold. In contrast, levels of the chromosome scaffold protein
      topoisomerase II at HSRs are the same as those found at other euchromatic
      locations. Metaphase chromosome condensation of the HSR is shown to be sensitive
      to topoisomerase II inhibitors, and sister chromatids often appear to remain
      attached within the HSRs at metaphase. We suggest that these features underlie
      anaphase bridging and the aberrant interphase structure of the HSR. The DHFR
      amplicon is widely used as a model system to study mammalian DNA replication. We
      conclude that the higher-order chromosome structure of this amplicon is unusual
      and suggest that caution needs to be exercised in extrapolating data from HSRs to
      normal chromosomal loci.

PMID- 10929197
TI  - A dicentric chromosome of Drosophila melanogaster showing alternate centromere
      inactivation.
AB  - Dicentric chromosomes are rarely found, because they interfere with normal cell
      division causing chromosome instability. By in situ hybridization of region
      specific heterochromatic yeast artificial chromosomes we have found that the
      artificially generated C(1)A chromosome of Drosophila melanogaster has two
      potential centromeres: one carries all the sequences of the centromere of the Y
      chromosome and the other carries only a part of the Y centromeric region that is
      rich in telomere-related sequences. Immunostaining with anti-Bub1 (a kinetochore
      specific marker) shows that, in spite of the differences in sequence, both
      centromeres can be active although as a rule only one at a time. In a small
      fraction of the chromosomes centromere inactivation is incomplete, giving rise to
      true dicentric chromosomes. The centromere inactivation is clonally inherited,
      providing a new example of epigenetic chromosome imprinting and the possibility
      of genetically dissecting this process. The involvement of telomere-related
      sequences in centromere function is discussed.

PMID- 10929198
TI  - Sex chromosome evolution in fish: the formation of the neo-Y chromosome in
      Eigenmannia (Gymnotiformes).
AB  - Chromosomes of a species of Eigenmannia presenting a X1X1X2X2:X1X2Y sex
      chromosome system, resulting from a Y-autosome Robertsonian translocation, were
      analyzed using the C-banding technique, chromomycin A3 (CMA3) and mithramycin
      (MM) staining and in situ digestion by the restriction endonuclease AluI. A
      comparison of the metacentric Y chromosome of males with the corresponding
      acrocentrics in females indicated that a C-band-positive, CMA3/MM-fluorescent and
      AluI digestion-resistant region had been lost during the process of
      translocation, resulting in a diminution of heterochromatin in the males. It is
      hypothesized that the presence of a smaller amount of G + C-rich heterochromatin
      in the sex chromosomes of the heteromorphic sex when compared with the
      homomorphic sex may be associated with the sex determination mechanism in this
      species and may be a more widely occurring phenomenon in fish with differentiated
      sex chromosomes than was initially thought.

PMID- 10929199
TI  - Aloe L.--a second plant family without (TTTAGGG)n telomeres.
AB  - The physical ends of chromosomes are protected and stabilised by telomeres. The
      sequence of telomeric DNA normally consists of a simple repeating unit that is
      conserved in many organisms. Most plants examined have been shown to possess
      Arabidopsis-type telomeres consisting of many repeat copies of the sequence 5'
      TTTAGGG-3'. Using fluorescent in situ hybridisation, slot blotting and the
      asymmetric polymerase chain reaction we demonstrate an absence of Arabidopsis
      type telomeres in the genus Aloe (family Asphodelaceae). The only other plant
      genera so far reported without such telomeres are Allium, Nothoscordum, and
      Tulbaghia (family Alliaceae). As these genera and Aloe are petaloid monocots in
      the Asparagales, it is suggested that an absence of Arabidopsis-type telomeres
      may be characteristic of this related group of plants.

PMID- 10929200
TI  - Cloning and characterisation of polymorphic heterochromatic segments of
      Brachycome dichromosomatica.
AB  - After selective enrichment and differential hybridisation of Cot-1 DNA fractions
      of plants with and without polymorphic heterochromatic segments, a repetitive
      sequence (called Bds1) specific to the polymorphic chromosome segments of
      Brachycome dichromosomatica (Brachyscome dichromosomatica) was isolated. A single
      repeat unit of Bds1 is 92 bp long and is organised in tandem arrays at three
      different polymorphic segment sites on the chromosomes of cytodeme A2. Although
      all three sites showed extensive polymorphism between plants, the karyotypes of
      all analysed mitotic root cells were stable within a single plant. Electron
      microscopy revealed heavily condensed chromatin structures at the most obvious
      polymorphic site. The mechanisms that generate and maintain the observed
      chromosome structure polymorphisms are discussed.

PMID- 10929201
TI  - Lemur chromosomal study with simultaneous R-banding and chromosome painting.
AB  - A method for simultaneously obtaining R-banding and chromosome painting is
      described. It combines fluorescence in situ hybridization with replication of R
      bands by 5-bromo-2'-deoxyuridine incorporation into synchronized cells.
      Distinctive R-banding induced by a modified fluorochrome-photolysis procedure can
      be observed on both painted and non-painted chromosomes. This method applied to
      Lemur chromosomes was developed for further studies of chromosomal changes in the
      evolution of prosimian primates and could also be used in other cytogenetic
      applications where simultaneous identification of chromosomal R-bands and
      hybridization signal is needed.

PMID- 10929202
TI  - Induction of tumor cell differentiation.
AB  - It is proposed that cell proliferation with reduced individual cell growth (total
      protein accumulation) is necessary, but not sufficient, for cell differentiation.
      These conditions may facilitate transcription and accumulation of histones H1
      and/or H1o relative to the core histones. This may have a critical role in cell
      differentiation.

PMID- 10929203
TI  - Characterization of a zebrafish (Danio rerio) desmin cDNA: an early molecular
      marker of myogenesis.
AB  - Desmin is a muscle-specific protein and a constitutive subunit of the
      intermediate filaments (IF) in skeletal, cardiac and smooth muscles. It is an
      early marker of skeletal muscle myogenesis. We have characterized a clone of
      desmin cDNA from an embryonic zebrafish (Danio rerio) cDNA library. The full
      length cDNA comprised 1798 nucleotides, encoding a protein of 473 amino acids.
      The predicted amino acid sequence of the zebrafish desmin shares a high degree of
      similarity to other vertebrate desmins, but also contains a sequence at the
      carboxyl terminal of the tail domain that is unique to the zebrafish. It carries
      many features which are distinctive of IF subunit proteins. These include the
      T/SSYRRXF/Y motif in the head domain, and the intermediate filament signature
      consensus, [I/V]-X-[T/A/C/I]-Y-[R/K/H]-X-[L/M]-L-[D/E], located in the carboxyl
      terminus of the central helical rod. Unlike other 3' UTR sequences, the 3' UTR of
      the zebrafish cDNA sequence has two CAYUG elements flanking a single
      polyadenylation site. The temporal and spatial expression patterns of desmin mRNA
      during early zebrafish development were studied. The onset of desmin expression
      occurred at the 1-3 somite stage (11 hpf). It increased throughout somitogenesis,
      with maximum expression at the Prim-6 stage (25 hpf), and decreasing expression
      towards the protruding-mouth stage (72 hpf). Desmin mRNA was initially localised
      exclusively to the somites, but was subsequently also detected in other
      musculature in the developing heart and fins. The onset of expression and the
      spatial localization of desmin mRNA in the zebrafish coincides with that reported
      for MyoD and myogenin.

PMID- 10929204
TI  - Transforming growth factor-beta 1 in the developing mouse pancreas: a potential
      regulator of exocrine differentiation.
AB  - Transforming growth factor-beta 1 (TGF-beta 1) is known to regulate cell growth,
      differentiation, and function in developing mammalian systems. Altering TGF-beta
      1 expression in the developing pancreas has been shown to affect both exocrine
      and endocrine development, suggesting that it is an important regulator of
      pancreatic organogenesis. We proposed to examine the ontogeny of TGF-beta 1 mRNA
      expression in the developing pancreas, as well as characterize the patterns of
      relative TGF-beta 1 gene expression and activity. We performed in situ
      hybridization for TGF-beta 1 on pancreas specimens obtained from CD-1 mice on
      gestational days 12.5 (E12.5), 15.5 (E15.5), and 18.5 (18.5). We also isolated
      mRNA from the pancreas on each of these days and performed a semi-quantitative
      reverse transcriptase polymerase chain reaction (RT-PCR) to assess relative TGF
      beta 1 expression as a function of gestational age. Finally, we performed a TGF
      beta 1 ELISA with media conditioned by embryonic pancreas from gestational days
      15.5 and 18.5. By in situ hybridization, TGF-beta 1 mRNA is expressed exclusively
      in the E12.5 pancreatic epithelium, sparing the surrounding mesenchyme. As
      pancreatic organogenesis progresses, TGF-beta 1 mRNA expression localizes
      predominantly to the developing acini. TGF-beta 1 gene expression appears modest
      through E15.5 but is upregulated near the end of gestation, at E18.5. TGF-beta 1
      activity, by ELISA, is also upregulated at E18.5. TGF-beta 1 may thus be a
      modulator of pancreatic organogenesis. Modest TGF-beta 1 expression through E15.5
      may be permissive for exocrine lineage selection. TGF-beta 1 expression may then
      become critical for terminal acinar differentiation. Upregulated TGF-beta 1
      expression at the end of gestation may be important for islet formation, and it
      may be necessary to inhibit continued proliferation and differentiation of
      pluripotent cells within the pancreatic ductal epithelium.

PMID- 10929205
TI  - Modification of mitochondrial metabolism in fibroblasts from mice with a skeletal
      muscle mutation (muscular dysgenesis). Evidence of embryonic communication
      between myoblasts and fibroblasts.
AB  - Muscle development during embryogenesis is a complex process involving many
      mechanisms. It requires a close communication among the different cellular types
      of the muscle, especially the fibroblasts and myoblasts. Indeed, any abnormality
      in one cell type might influence the differentiation of the other. Thus, any
      disturbance altering the metabolism of the myoblasts might lead to modifications
      in the fibroblasts. To study this phenomenon, we used the dysgenic mouse (mdg
      "muscular dysgenesis") carrying a homozygous recessive lethal mutation expressed
      only in skeletal muscle cells. First, we found that fibroblasts isolated from
      such mutant muscle (and not from mutant skin tissue) and grown in culture
      exhibited an altered metabolism. Secondly, muscle fibroblasts showed a lower
      capacity for proliferation. We also observed that respiration and ATP synthesis
      of dysgenic muscle fibroblasts were deficient, while respiratory chain enzymatic
      activities were normal. Finally, intracellular [Ca2+] levels of dysgenic
      fibroblasts are 50% of those of normal fibroblasts. These results support the
      hypothesis that certain characteristics of fibroblasts are determined by the
      surrounding cellular environment during embryonic organogenesis, and that such
      modifications are stable when the fibroblasts are isolated in vitro. Since
      fibroblast differentiation was disrupted permanently, this suggests, in the case
      of myopathies, that the modified cells, surrounding the muscle tissue, could
      contribute to the muscle pathology. Synergistic activities of this type should be
      considered when studying the course of pathologies in different types of muscle
      diseases.

PMID- 10929206
TI  - Spontaneous retinoic acid receptor beta 2 expression during mesoderm
      differentiation of P19 murine embryonal carcinoma cells.
AB  - Exposure of aggregated murine P19 embryonal carcinoma cells to dimethylsulfoxide
      (DMSO) induces mesoderm and both embryonic cardiac and skeletal muscle
      differentiation, while retinoic acid (RA) is an inducer of neuroectodermal
      differentiation. P19 cells constitutively express the retinoic acid receptor
      alpha (RAR alpha) and RAR gamma mRNAs while RAR beta expression is induced by RA
      through a consensus RA-response element in the RAR beta promoter. In the present
      study we show that the RAR beta transcript is strongly expressed in both P19
      cells and in a RA-nonresponsive derivative of P19 cells, called RAC65, during
      DMSO-induced mesoderm and muscle differentiation. Reverse transcriptase
      polymerase chain reaction analysis indicated that RAR beta 2 is the predominant
      isoform expressed in DMSO-differentiated cells, providing the first evidence for
      RA-independent regulation of RAR beta 2 transcript levels. Immunoblot analysis
      showed a 3-fold increase in the RAR beta protein expression over basal levels in
      differentiated cells, and immunohistochemistry indicated that all cells in the
      culture including muscle reacted positively for the RAR beta protein. RAR beta 2
      transcript expression was differentiation-dependent and occurred without
      transactivation of a transfected RARE beta 2 reporter gene. Little transcription
      of the RAR beta gene was detected in nuclear run-off assays of undifferentiated
      P19 cells and only a small increase in transcription was observed in nuclei from
      DMSO-treated cells. RA treatment of P19 cells stably transfected with the RA
      responsive element from the RAR beta gene showed that RAR beta 2 mRNA expression
      during DMSO differentiation was associated with increased sensitivity to RA.
      Together these data show that RAR beta 2 is expressed spontaneously in an
      apparently RA-independent manner in differentiating mesoderm and mesoderm
      derivatives, resulting in increased sensitivity to RA in these cells.

PMID- 10929207
TI  - Type XVIII collagen is newly transcribed during bovine adipogenesis.
AB  - To isolate candidate genes concerned with bovine adipocyte differentiation, we
      have constructed a subtraction cDNA library from a clonal bovine intramuscular
      preadipocyte (BIP) cell line. We have isolated a set of cDNA clones whose
      respective mRNA levels are upregulated during the differentiation of BIP cells.
      The sequence of one subtracted cDNA fragment was highly homologous to that of
      mouse type XVIII collagen. Northern blot analysis and reverse transcriptase
      polymerase chain reaction (RT-PCR) showed that collagen XVIII gene expression
      increased during adipocyte differentiation. The collagen XVIII gene was also
      highly expressed in fat tissue. Although its function is unclear, these
      expression patterns indicate that type XVIII collagen may be associated with
      adipocyte differentiation in cattle.

PMID- 10929208
TI  - Endothelial-like cells derived from human CD14 positive monocytes.
AB  - In the present study, we show that endothelial-like cells (ELCs) can develop from
      human CD14-positive mononuclear cells (CD14 cells) in the presence of angiogenic
      growth factors. The CD14 cells became loosely adherent within 24 h of culture and
      subsequently underwent a distinct process of morphological transformation to
      caudated or oval cells with eccentric nuclei. After 1 week in culture the cells
      showed a clear expression of endothelial cell markers, including von Willebrand
      factor (vWF), CD144 (VE-cadherin), CD105 (endoglin), acetylated low-density
      lipoprotein (AC-LDL)-receptor, CD36 (thrombospondin receptor), FLT-1, which is
      vascular endothelial cell growth factor (VEGF) receptor-1, and, to a weaker
      extent, KDR (VEGF receptor-2). Furthermore, in these cells structures resembling
      Weibel-Palade bodies at different storage stages were identified by electron
      microscopy, and upon culturing on three-dimensional fibrin gels the cells build
      network-like structures. In addition, cell proliferation and vWF expression was
      stimulated by VEGF, and the endothelial cell adhesion molecules CD54 (ICAM-1),
      and CD106 (VCAM-1) became transiently inducible by tumor necrosis factor-alpha
      (TNF-alpha). In contrast, the dendritic markers CD1a, and CD83 were not expressed
      to any significant extent. The expression of CD68, CD80 (B7-1), CD86 (B7-2), HLA
      DR and CD36 may also suggest that ELCs might be related to macrophages, sinus
      lining or microvascular endothelial cells. Taken together, our observations
      indicate that ELCs can differentiate from cells of the monocytic lineage,
      suggesting a closer relationship between the monocyte/macrophage- and the
      endothelial cell systems than previously supposed.

PMID- 10929209
TI  - Effects of physical and apnea training on apneic time and the diving response in
      humans.
AB  - The aim of this investigation was to study separately the effects of physical
      training and apnea training on the diving response and apneic time in humans.
      Both types of training have been suggested to lead to prolonged apneic time and
      an increased "diving response" (i.e., regional vasoconstriction and bradycardia).
      The study was also designed to examine the effects of these two types of training
      on the characteristics of the increase in apneic time with repeated apneas.
      Simulated diving tests were performed before and after the different training
      programs. The test format was one apnea and five apneas with facial immersion in
      cold water at 2-min intervals. An increase in apneic time was observed after
      physical training (n = 24), and this was attributable to an increased time beyond
      the physiological breaking point. The other parameters that were measured
      remained unaffected. After apnea training (n = 9), however, apneic time was
      increased by a delay in the physiological breaking point, which is mainly
      determined by the arterial tension of CO2. The diving response had increased, and
      the effect of repeated apneas on apneic time tended to be larger after apnea
      training. These results may explain the pronounced diving responses and long
      apneas observed in trained apneic divers.

PMID- 10929211
TI  - Oxygen kinetics and modelling of time to exhaustion whilst running at various
      velocities at maximal oxygen uptake.
AB  - The purpose of this study was to characterise the relationship between running
      velocity and the time for which a subject can run at maximal oxygen uptake
      (VO2max), (tlimVO2max). Seven physical education students ran in an incremental
      test (3-min stages) to determine VO2max and the minimal velocity at which it was
      elicited (vVO2max). They then performed four all-out running tests on a 200-m
      indoor track every 2 days in random order. The mean times to exhaustion tlim at
      90%, 100%, 120% and 140% vVO2max were 13 min 22 s (SD 4 min 30 s), 5 min 47 s (SD
      1 min 50 s), 2 min 11 s (SD 38 s) and 1 min 12 s (SD 18 s), respectively. Five
      subjects did not reach VO2max in the 90% vVO2max test. All the subjects reached
      VO2max in the runs at 100% vVO2max. All the subjects, except one, reached VO2max
      in the runs at 120% vVO2max. Four subjects did not reach VO2max in the 140%
      vVO2max test. Time to achieve VO2max was always about 50% of the time to
      exhaustion irrespective of the intensity. The time to exhaustion-velocity
      relationship was better fitted by a 3- than by a 2-parameter critical power model
      for running at 90%, 100%, 120%, 140% vVO2max as determined in the previous
      incremental test. In conclusion, tlimVO2max depended on a balance between the
      time to attain VO2max and the time to exhaustion tlim. The time to reach VO2max
      decreased as velocity increased. The tlimVO2max was a bi-phasic function of
      velocity, with a peak at 100% vVO2max.

PMID- 10929210
TI  - Erythropoietin acute reaction and haematological adaptations to short,
      intermittent hypobaric hypoxia.
AB  - This study aimed to determine whether brief hypoxic stimuli in a hypobaric
      chamber are able to elicit erythropoietin (EPO) secretion, and to effectively
      stimulate erythropoiesis in the short term. In two different experiments, a set
      of haematological, biochemical, haemorheological, aerobic performance, and
      medical tests were performed in two groups of healthy subjects. In the first
      experiment, the mean plasma concentration of EPO ([EPO]) increased from 8.7 to
      13.5 mU.ml-1 (55.2%; P < 0.01) after 90 min of acute exposure at 540 hPa, and
      continued to rise until a peak was attained 3 h after the termination of hypoxia.
      In the second experiment, in which subjects were exposed to a simulated altitude
      of up to 5500 m (504 hPa) for 90 min, three times a week for 3 weeks, all
      haematological indicators of red cell mass increased significantly, reaching the
      highest mean values at the end of the programme or during the subsequent 2 weeks,
      including packed cell volume (from 42.5 to 45.1%; P < 0.01), red blood cell count
      (from 4.55 x 10(6) to 4.86 x 10(6).l-1; P < 0.01), reticulocytes (from 0.5 to
      1.4%; P < 0.01), and haemoglobin concentration (from 14.3 to 16.2 g.dl-1; P <
      0.01), without an increase in blood viscosity. Arterial blood oxygen saturation
      during hypoxia was improved (from 60% to 78%; P < 0.05). Our most relevant
      finding is the ability to effectively stimulate erythropoiesis through brief
      intermittent hypoxic stimuli (90 min), in a short period of time (3 weeks),
      leading to a lower arterial blood desaturation in hypoxia. The proposed mechanism
      for these haematological and functional adaptations is the repeated triggering
      effect of EPO production caused by the intermittent hypoxic stimuli.

PMID- 10929212
TI  - An improved estimation of mean body temperature using combined direct calorimetry
      and thermometry.
AB  - The conventional method used to estimate the change in mean body temperature
      (dMBT) is by taking X% of a body core temperature and (1-X)% of weighted mean
      skin temperature, the value of X being dependent upon ambient temperature. This
      technique is used widely, despite opposition from calorimetrists. In the present
      paper we attempt to provide a better method. Minute-by-minute changes in dMBT, as
      assessed using calorimetry, and 21 (20 if esophageal temperature was unavailable)
      various regional temperatures (dRBTs), as assessed using thermometry, including 6
      subcutaneous measures, were collected from 7 young male adults at 6 calorimeter
      temperatures. Since a calorimeter measures only changes in heat storage, which
      can be converted to dMBT, all body temperatures are expressed as changes from the
      reasonably constant pre-exposure temperatures. The following three aspects were
      investigated. (1) The prediction of dMBT from the 21 (or 20) dRBTs with multi
      linear regression analysis (MLR). This yields two results, model A with rectal
      temperature (dTre) alone, and model B with dTre and esophageal temperature
      (dTes). (2) The prediction of dMBT from dTre with or without dTes and 13 skin
      surface temperatures combined to one weighted mean skin temperature (dTsk), using
      MLR. This results in models C and D. Six more models (E-J) were added,
      representing the above two sets in various combinations with four factors. (3)
      The conventional method calculated with four values for X. Model A predicted
      better than 0.3 degree C in 70% of the cases. Model I was the best amongst the
      models with 13 weighted skin temperatures (better than 0.3 degree C in 60% of the
      cases). The conventional method was erratic.

PMID- 10929213
TI  - Effects of 17 days bedrest on the maximal voluntary isometric torque and
      neuromuscular activation of the plantar and dorsal flexors of the ankle.
AB  - Maximal voluntary isometric torque values of the ankle plantar (Tim,PF) and
      dorsal flexors (Tim,DF) were assessed in eight healthy adult males at 5 degrees
      and 15 degrees of dorsal flexion (DF) and at 5 degrees, 15 degrees and 25 degrees
      of plantar flexion (PF) with the knee at right angles, before (two times), during
      (three times) and after (three times) 17 days of 6 degrees head-down tilt bedrest
      (BR). Integrated electromyograms (iEMG) were also recorded from the gastrocnemius
      medialis and tibialis anterior. Tim,PF and the iEMG of the gastrocnemius medialis
      were significantly larger (by 14% and by 27%, respectively) at the end of
      recovery than before BR. This was probably the consequence of training and/or
      habituation leading to: (1) increased activation of the plantar flexors; and (2)
      decreased co-activation of the antagonist muscles. Neither Tim,DF nor the
      tibialis anterior iEMG changed significantly. The effects of BR on muscle
      performance were evaluated as follows. The net torque generated by a given muscle
      group was assumed to be the algebraic sum of the torque generated by the agonists
      and by the antagonists. Thus, for the plantar flexors Tim,PF = alpha iEMGGm -
      beta iEMGTa, where: (1) iEMGGm and iEMGTa are the iEMGs of gastrocnemius medialis
      and of tibialis anterior during maximal PF; and (2) the constants alpha and beta
      represent the electromechanical coupling of the plantar (alpha) and dorsal (beta)
      flexors. Similarly for the dorsal flexors: Tim,DF = beta iEMGTa - alpha iEMGGm,
      where iEMGTa and iEMGGm are the iEMGs of tibialis anterior and gastrocnemius
      medialis during maximal DF. Torque and iEMG values were assessed for all subjects
      under all experimental conditions. Thus, since the biomechanical leverage of the
      system was constant, alpha and beta could be calculated. During BR, alpha
      decreased by 25% and it dropped by a further 30% during recovery. In contrast,
      beta remained almost unchanged. This suggests that, in spite of training and/or
      habituation, BR significantly impaired the maximal isometric performance of the
      plantar flexors, an effect that continued during the initial 10 days of recovery.

PMID- 10929214
TI  - Recovery of skeletal muscle contractility after high- and moderate-intensity
      strength exercise.
AB  - To examine neuromuscular fatigue and recovery, ten male strength athletes [mean
      (SE) 27.5 (1.4) years] performed a moderate- and a high-intensity strength
      exercise protocol. In the high-intensity protocol, the load was 100% of the
      subject's three-repetition maximum (3-RM) for squats and front squats, and 100%
      of the subject's 6-RM for knee extensions. In the moderate-intensity protocol,
      the load was 70% of the high-intensity protocol, and both protocols lasted 90
      min. The contractile properties of the leg extensor muscles were tested using
      isokinetic knee extensions, electrical stimulation, and squat jumps. Tests were
      done before exercise, 5-20 min after exercise, and frequently for 33 h after
      exercise. The decrements in knee extension performance were greater after the
      high-intensity protocol (12-14%), as compared to the moderate-intensity protocol
      (6-7%, P < 0.01). Similar decrements were seen in squat-jumping performance after
      the high-intensity protocol. Decrements in electrically evoked force were also
      greatest after the high-intensity protocol (P < 0.05), and were more pronounced
      at 20 Hz stimulation than at 50 Hz stimulation (P < 0.05). The recovery of
      performance showed a biphasic pattern, with a rapid recovery within the first 11
      h after exercise, followed by a leveling off or a second drop in performance 11
      22 h after exercise. All variables were back to baseline by 3 h after the
      moderate-intensity protocol, while all variables were back to baseline by 33 h
      after the 100% protocol. The role of structural changes (excitation-contraction
      coupling and contractile proteins) in the long-lasting performance decrements
      seen after the high-intensity protocol is discussed.

PMID- 10929215
TI  - Strength training with partial ischaemia stimulates microvascular remodelling in
      rat calf muscles.
AB  - The effects of strength training with partial tourniquet ischaemia on skeletal
      muscle capillarity were examined, particularly in terms of the distribution of
      arteriolar and venular capillaries and their capillary domain area, in male
      Wistar rats. A tourniquet applied around the knee joint induced partial
      ischaemia. Repeated isometric contractions of calf muscles, 1 s on/1 s off for 3
      min, induced by electrical stimulation (100 Hz), were conducted 2 days/week for 6
      weeks as training. Morphologic data were obtained from four groups; non-treatment
      control (C), ischaemic (IS), non-ischaemic training (NIT) and ischaemic training
      (IT). In the superficial portion of gastrocnemius (GASs) muscle, the total
      capillary density of arteriolar capillaries was significantly greater in the IT
      leg than in the C-leg (P < 0.05). In the plantaris (PL) muscle, these values were
      significantly greater in the IT-leg than in both the C- and NIT-legs (P < 0.05).
      Only in the GASs was the capillary-to-fibre ratio significantly greater in the IT
      leg than in the C-leg (P < 0.05). In GASs and PL, the capillary domain area (CDA)
      was smaller in the IT-leg than in the C- and NIT-legs. In all muscles examined,
      mean fibre cross-sectional area was not significantly changed by the experimental
      treatment. These findings suggest that adaptive changes in the microvascular
      network, identified as an increase in the arteriolar capillary area and a
      reduction in diffusion distance, occur in the skeletal muscles after strength
      training with partial ischaemia. These adaptive changes probably improve the
      supply of oxygen and nutrients to skeletal muscle tissues.

PMID- 10929216
TI  - No acute effects of short-term creatine supplementation on muscle properties and
      sprint performance.
AB  - In a double-blind, placebo, controlled study, we investigated the acute effects
      of short-term oral creatine supplementation (20 g.day-1 for 6 days) on muscle
      activation, fatigue and recovery of the m. quadriceps femoris during electrical
      stimulation, and on maximal performance during sprint cycling. The quadriceps
      muscles of 23 well-trained rowers were stimulated at different frequencies (10,
      20, 50, 100, 150 and 200 Hz). Furthermore, 40 repetitive, electrically stimulated
      (duration 220 ms, stimulation frequency 150 Hz) concentric contractions were
      imposed at a constant angular velocity of 180 degrees.s-1 over a range of 50
      degrees (from 90 to 140 degrees knee angle), each extension/flexion cycle lasting
      1200 ms. To determine recovery, torque was measured at 20, 50, 80, 120, 180 and
      300 s after the last contraction. In addition, two maximal 30-s sprints were
      performed on a cycle ergometer with 4 min rest in between. Following short-term
      creatine supplementation, body mass [mean (SEM)] increased (P < 0.05) from 85.7
      (2.7) kg to 87.3 (2.9) kg. Creatine supplementation had no effect on maximal
      voluntary isometric torque and muscle activation, or on fatigue and recovery of
      dynamic exercise. There was also no significant effect on peak power, time to
      peak power and work to peak power, or total work during both sprints on the cycle
      ergometer. It was concluded that short-term oral creatine supplementation
      resulted in increased body mass, but did not enhance muscle performance or
      maximal output during sprint cycling.

PMID- 10929217
TI  - Gender differences in sweat lactate.
AB  - Sweat rate may affect sweat lactate concentration. The current study examined
      potential gender differences in sweat lactate concentrations because of varying
      sweat rates. Males (n = 6) and females (n = 6) of similar age, percentage body
      fat, and maximal oxygen consumption (VO2max) completed constant load (CON)
      cycling (30 min--approximately 40% VO2max) and interval cycling (INT) (15 1-min
      intervals each separated by 1 min of rest) trials at 32 (1) degrees C wet bulb
      globe temperature (WBGT). Trials were preceded by 15 min of warm-up (0.5 kp, 60
      rpms) and followed by 15 min of rest. Blood and sweat samples were collected at
      15, 25, 35, 45, and 60 min during each trial. Total body water loss was used to
      calculate sweat rate. Blood lactate concentrations (CON approximately equal to 2
      mmol.l-1, INT approximately equal to 6 mmol.l-1) and sweat lactate concentrations
      (CON and INT approximately equal to 12 mmol.l-1) were not significantly different
      (P > 0.05) at any time between genders for CON or INT. Overall sweat rates (ml.h
      1) were not significantly different (P > 0.05) between trials but were
      significantly greater (P < or = 0.05) for males than for females for CON [779.7
      (292.6) versus 450.3 (84.6) ml.h-1] and INT [798.0 (268.3) versus 503.0 (41.4)
      ml.h-1]. However, correcting for surface area diminished the difference [CON:
      390.7 (134.4) versus 277.7 (44.4) ml.h-1, INT: 401.5 (124.1) versus 310.6 (23.4)
      ml.h-1 (P < or = 0.07)]. Estimated total lactate secretion was significantly
      greater (P < or = 0.05) in males for CON and INT. Results suggest that sweat rate
      differences do not affect sweat lactate concentrations between genders.

PMID- 10929219
TI  - Transferability of workload measurements between three different types of
      ergometer.
AB  - The aim of this study was to test the transferability of workload measurements
      between three different types of bicycle ergometer. Two common ergometers (Lode
      Excalibur and Avantronic Cyclus 2) were compared with a powermeter (Schoberer SRM
      system) that enables the measurement of power output during road cycling. Twelve
      well-trained subjects participated in this study. Within 12 h, each subject
      carried out three separate graded incremental exercise tests on each of the
      ergometric devices, and their oxygen uptake (VO2) and heart rate were determined.
      The three test protocols were identical: after warm-up, four stages of 4 min each
      at exercise intensities of 100, 150, 200, and 250 W. Pedalling frequency was
      controlled and there was no difference between the three ergometers. Tests were
      administered in a random order. Neither VO2 nor heart rate was affected by the
      type of ergometer used. For a given intensity, the same values were found in the
      two laboratory tests and in the field test (VO2: P = 0.425; heart rate: P =
      0.845). Thus, the transferability of workload measurements between two different
      laboratory cycling ergometers and an ambulatory device was proven. Equivalency
      was determined using VO2 and heart rate as indices of metabolic and
      cardiovascular strain, respectively.

PMID- 10929218
TI  - Sonographic studies of human soleus and gastrocnemius muscle architecture: gender
      variability.
AB  - The purpose of this study was to establish if there are gender differences in
      muscle architecture in relaxed human soleus and gastrocnemius muscles of normal,
      live subjects. Ultrasonography was used to measure fiber bundle length, muscle
      thickness, and angles of pennation in a total of ten predetermined sites in the
      medial and lateral heads of gastrocnemius and the anterior and posterior soleus
      in 19 males and 16 females. Percentage differences between males and females for
      each parameter were recorded. Gender differences were statistically analyzed
      using multivariate analysis of variance. In the gastrocnemius and soleus muscles
      of males and females the differences between the overall fiber bundle length,
      angle of pennation and muscle thickness were statistically significant (P <
      0.05). Overall, females were found to have longer average muscle fiber bundle
      length and males thicker muscles and larger angles of pennation. The greatest
      percentage differences of the architectural parameters between males and females
      were in the posterior soleus: 13% difference in fiber length and 26% difference
      in angle of pennation in the midline of posterior soleus and 26% difference in
      muscle thickness of the lateral part of posterior soleus. No correlation was
      found between leg length and fiber length, angle of pennation or muscle
      thickness. Fiber length (decreased), angle of pennation (greater) and muscle
      thickness (greater) of most parts of the gastrocnemius and soleus muscles were
      significantly different in males and females. Leg length of males and females did
      not correlate to these architectural parameters.

PMID- 10929220
TI  - Body surface area: Du Bois and Du Bois revisited.
AB  - The Du Bois and Du Bois body surface area (BSA) equation is used widely to
      normalise physiological parameters. However, that only nine subjects were used in
      its derivation does not appear to be well known and does not justify its
      ubiquitous application. Furthermore, the derivation appears to be hampered by a
      lack of modern statistical methods and the omission of a large amount of
      available data. We have shown that the omitted data, obtained by measurement of
      the length of body parts, were identical to the data obtained by encasing
      subjects in moulds ?BSA (moulds; cm2) = [1.00 (0.02)] x BSA (linear measurements)
      + [123 (347)]?. Non-linear regression analysis of the BSA of all 42 subjects
      reported by Du Bois and Du Bois gave new values for the constants of the model
      ?BSA (cm2) = 94.9 x [weight (kg)0.441] x [height (cm)0.655]?. Although the
      original equation obtained by Du Bois and Du Bois was found to be adequate in
      adults, we recommend that it should not be used in daily practice, owing to the
      low number of subjects used in its derivation. The work presented here has placed
      the original results of Du Bois and Du Bois on a more robust statistical footing,
      yielding values for the model constants that would have been obtained if Du Bois
      and Du Bois had had access to modern statistical methods.

PMID- 10929221
TI  - [(Ultrasound guided) fine-needle puncture cytology in the area of the head and
      neck].

PMID- 10929222
TI  - [Value of fine needle puncture cytology in neoplasms of the parotid gland].
AB  - BACKGROUND: In many parts of Germany fine-needle aspiration biopsy (FNAB) is
      still not part of the routine preoperative diagnostic evaluation of salivary
      gland neoplasms. Most opponents consider the study unnecessary and recommend that
      all salivary gland neoplasms should be excised. OBJECTIVE: Because of this an
      evaluated the ability of FNAB to provide an accurate diagnosis of parotid gland
      neoplasms. PATIENTS AND METHOD: Between January 1992 and October 1995, 336
      patients referred for operative therapy of salivary gland neoplasms underwent
      retrospective analysis of preoperative FNAB compared with the excised tumor
      histology. RESULTS: Results showed that the FNAB had a sensitivity of 93.1%, a
      specificity of 99.2%, a positive predictive value of 93.1%, a negative predictive
      value of 99.2% and an accuracy of 98.6%. Complications were observed in less than
      1%. DISCUSSION: Our findings demonstrated that the FNAB is a safe diagnostic tool
      that has a reliable sensitivity and high specificity for the assessment of
      salivary gland pathology. Since many malignant salivary gland neoplasms present
      with a virtual lack of symptoms indicating actual malignancy we believe that
      there is need for FNAB in routine preoperative diagnostic testing.

PMID- 10929223
TI  - [Epithelialization model of non-biological tissue replacement materials in
      vitro].
AB  - Successful use of non-biologic implants in reconstructive head and neck surgery
      is dependent on tissue compatibility and epithelization. This is true not only
      for epithelial cells, but also for mesenchymatic cells. Therefore we tested
      several substrates with human fibroblasts or keratinocytes from the oral mucosa
      in cell culture. In tissue culture keratinocyte outgrowth from small mucosal
      flaps onto the surface was observed. Preparations were evaluated by histology and
      scanning electron microscopy. Cellulose-ester, polyvinylidene-difluoride and
      polyglactin developed monolayers of fibroblasts and keratinocytes in cell
      cultures. In tissue culture mucosal flaps showed good adherence to the surface of
      these materials and a fine outgrowth of keratinocytes. Expanded polytetrafluor
      ethylene (ePTFE) was partially covered by a layer of fibroblasts and
      keratinocytes in cell culture, but cell adherence was not sufficient. In tissue
      culture the mucosal flaps failed to attach on ePTFE. These results illustrate
      that the mesenchymatic and epithelial component of cell and tissue cultures show
      different qualities of cellular adherence and growth on the surface of non
      biologic implants. We propose our method for the development of an in-vitro model
      for the epithelization of non-biologic implantation materials.

PMID- 10929224
TI  - [Dependence of uni- and bilateral olfactory capacity on nasal airflow in patients
      with chronic rhinosinusitis].
AB  - OBJECTIVE: Olfactory dysfunction is a common finding in patients with chronic
      rhinosinusitis (CRS). The aim of this study was to investigate the relationship
      between olfaction and nasal flow as determined by active anterior rhinomanometry
      (AAR). METHODS: Thirty patients with CRS were included in this series. Patients'
      histories and subjective assessments of olfaction were documented with
      questionnaires. Smell tests, assessments of olfaction, AAR, and results of
      rhinoscopy were recorded, including odor identification, discrimination and
      thresholds measured with the "Sniffin' Sticks"-test. RESULTS: CRS influenced
      olfactory performances variably in the different tests: 10% of the patients had
      pathologic rates of odor discrimination, compared with 34% in odor identification
      and 73% in thresholds. Statistical analyses (using Spearman's test) indicated a
      significant correlation between nasal airflow and odor identification screening
      (r29 = 0.56, P < 0.01) and n-butanol-threshold (r29 = 0.44, P < 0.05),
      respectively. CONCLUSION: Olfactory performance in CRS was correlated to several
      parameters of nasal airflow measured with AAR. The n-butanol threshold test
      revealed the most frequent pathological results and may best be used for
      detecting olfactory disorders. However, because a number of factors may influence
      olfactory dysfunction in CRS, our findings must be evaluated in a lager series.

PMID- 10929225
TI  - [Micronuclei as biological markers for the detection of local cancer
      transformation in the upper aerodigestive tract].
AB  - A lot of different endogenous and exogenous factors are accused to promote
      squamous cell carcinomas in the upper aerodigestive tract. Main risk factors are
      the chronic tobacco- and alcohol consumption. The fact, that many patients
      develop syn- or metachronic carcinomas in this area was first described by
      Slaughter et al. 1953 and explained with the phenomenon of field cancerisation.
      Concerning to this hypothesis the whole mucosa of the upper aerodigestive-tract
      is premalignant damaged. In our study the micronucleus-frequency was determined
      as a biomarker for the genetic injury to prove the fieldcancerisation on the
      cellular level at 159 people (control-group, abuser, patients with HNSCC). Our
      results confirm the hypothesis of fieldcancerisation of the mucosa of the upper
      aerodigestive-tract at strong tobacco- and alcohol consumers and patients with
      head and neck squamous cell carcinoma. Furthermore there is a highly
      statistically significant correlation between increasing micronucleus frequency
      and increasing tobacco abuse. As a final result of our study the micronucleus
      assay seems to be of good value to show a genotoxic damage in healthy mucosa at
      people with a high risk to develop HNSCC, but it's not usable to give any answer
      if and when such carcinomas arise.

PMID- 10929226
TI  - [Improved prognostic assessment of head-neck carcinomas by new genetic markers].
AB  - In individual patients with head and neck squamous cell carcinomas (HNSCC),
      established prognostic factors do not satisfactorily predict clinical outcome.
      For the first time we investigated a total of 100 HNSCC by Comparative Genomic
      Hybridization (CGH) to define chromosomal alterations that are associated with
      the patients prognosis. Patients were followed for at latest 4 but at least 2
      years after surgery or until death. During this observation period twenty-nine of
      them died because of cancer disease. The Kaplan-Meier method was used plotting
      survival curves for every single chromosomal alteration as well as every clinico
      pathological parameter. The curves were tested for significance by the log rank
      as well as the Breslow test. Significance of particular prognostic parameters was
      then evaluated by the Cox regression model. The overall survival time as well as
      the recurrence free survival time were significantly lower in patients who's
      tumors showed amplifications of the chromosomal region 11q13 (p = 0.0008 for LR
      and p = 0.0024 for B). The survival time of the patients was also lower if the
      carcinomas carried over-representations of chromosome 3q (p = 0.0299 for LR and p
      = 0.0546 for B). Multivariate analysis (Cox's proportional hazards model)
      revealed both alterations as most important independent prognostic factors in
      HNSCC. None of the conventional clinicopathological parameters (pT-, pN-status,
      UICC stage, grading) achieved statistical significance in the multivariate model.
      These results suggest that in HNSCC the occurrence of 11q13 amplification and 3q
      overrepresentation are highly significant independent prognostic markers and of
      better value than the established TNM and grading criteria.

PMID- 10929227
TI  - [Effect of fibroblast growth factor-1 (FGF-1) on spiral ganglion cells of the
      mammalian cochlea].
AB  - Transient expression by hair cells, increasing levels of FGF-1 mRNA in neonatal
      rat spiral ganglion neurons and strong expression in adulthood, make FGF-1 a
      candidate to be associated with development and maintenance of the mammalian
      spiral ganglion. To test this hypothesis, dissociated spiral ganglion cells from
      5 day old rats were cultured in the presence of FGF-1 at 100 ng/ml plus heparan
      sulfate proteoglycans (HSPG) at 500 ng/ml for 72 hours. Spiral ganglion cells
      incubated with FGF-1/HSPG achieved an average neurite length of 323 microns while
      control cells gained an average neurite length of 203 microns. The results of
      this study are consistent with our previous findings in whole spiral ganglion
      explants (3) where FGF-1 incubation significantly stimulated neurite outgrowth at
      about the same range. However, stimulation of neurite outgrowth in dissociated
      spiral ganglion cells suggests that FGF-1 directly binds to FGF receptors on the
      surface of spiral ganglion neurons and/or neurites instead of acting via
      intermediate cells such as glia. Since FGF receptor mRNA was found to be
      expressed only at very low levels in neonatal spiral ganglion neurons (7) it is
      possible that the receptors are highly localized, perhaps to neurite growth
      cones. Alternatively, an unknown FGF receptor or splice variant may be expressed
      in these cells. Adequate FGF-1 application to the human inner ear may stimulate
      spiral ganglion cell survival and neurite extension after hair cell loss in
      patients suitable for cochlear implant treatment. By creating a closer contact
      between spiral ganglion cells and the electrode, FGF-1 might also improve the
      efficacy of cochlear implants.

PMID- 10929228
TI  - [Similarity of monozygotic twins regarding vocal performance and acoustic markers
      and possible clinical significance].
AB  - Auditory similarities in voices of monozygotic twins have already been described
      in the literature. However, is there a clinical relevance? Thus, the present
      study was designed to identify parameters of vocal performance and acoustic
      features which are significantly more similar in monozygotic twins than in non
      related persons. In our hypothesis, comparable prerequisites for an increased
      vocal load in a profession or in an artistic education of the voice could be due
      to these similarities. We compared intra-pair differences with data from a
      control group. Moreover, we examined the correlation of intra-pair differences
      with the age of the monozygotic twins. A greater difference in older twin pairs
      than in younger pairs could show the effect of an exogene influence. In addition
      to the few phoniatric studies in twins in the literature, we used current methods
      for acoustic analysis. We examined seven parameters of vocal performance and
      three acoustic features in 31 monozygotic twin pairs (median age 36 years, range
      18-75 years) and compared them with 30 control group pairs, which consisted of
      non-related persons of the same age and sex, newly combined from the group of
      monozygotic twins ("statistical twins"). We found significant differences in
      seven of ten parameters (vocal range, highest and lowest vocal fundamental
      frequency, fundamental speaking frequency, maximum voice intensity, number of
      partials, vibrato of intensity; U-test by Mann-Whitney). No correlation of the
      differences of the identical twins with age was found in the examined parameters.
      The voices of identical twins are significantly more similar than those of non
      related persons regarding the above mentioned features. Thus, the suitability of
      the voices of monozygotic twins for professions with a high demand on voice is
      comparable. Results of the group comparison correlate largely with the
      literature. The missing correlation with age could be due to the fact that the
      environmental effects were not measurable, and/or the development of the voice is
      more influenced by genetic effects.

PMID- 10929229
TI  - [Squamous epithelial carcinoma in a duct cyst of the submandibular gland].
AB  - Squamous cell carcinomas are rare malignant tumors of the major and minor
      salivary glands in the head region. This is the report of a squamous cell
      carcinoma within a cyst of the submandibular gland. Clinical, histological and
      immunohistochemical findings are presented, and the importance as well as the
      therapeutic strategy of this very rare malignant tumor of the salivary glands are
      discussed.

PMID- 10929230
TI  - [Unilateral neck swelling of uncertain origin. Pharyngocele].

PMID- 10929231
TI  - [Emergency management in general ENT practice. 3: Special emergencies B].

PMID- 10929232
TI  - [Chemosensory evoked potentials for clinical diagnosis of olfactory disorders].

PMID- 10929233
TI  - DNA Commission of the International Society for Forensic Genetics: guidelines for
      mitochondrial DNA typing.

PMID- 10929234
TI  - Electrocardiographic changes in ex-prisoners of war released from detention
      camps.
AB  - The aim of the study was to determine whether and to what extent changes in the
      electrocardiograms occurred in released prisoners of war (POWs) from Serbian
      detention camps and whether the frequency of occurrence differed from similar
      changes in a control group. An electrocardiogram was recorded and medical
      examinations conducted on 182 randomly selected ex-POWs. The subjects were male
      with a mean age of 35.8 +/- 11.0 years, age range 18-65 years and the average
      length of imprisonment 164.5 +/- 87.1 days. The electrocardiograms were analysed
      according to the Minnesota code. The following changes were frequently found:
      postinfarction Q-wave in 3.3%, control 1.1% (not significant), ST-segment
      depression horizontal or descendent in 14.3% (controls 3.8%, P < 0.01),
      particularly S-T segment depression of up to 0.5 mm in 12.1% (controls 2.2%, (P <
      0.01), total negative T-wave in 7.1% (control group 3.3%, not significant), total
      arrhythmia 18.1% (controls 7.1%, P < 0.01), particularly ventricular premature
      beats in 2.2% (controls 0.5%, not significant), incomplete left bundle-branch
      block 2.2% (not registered in the control group), complete left bundle-branch
      block in 0.5% (not registered in the control group), sinus tachycardia in 12.1%
      (controls 6.6%, not significant), sinus bradycardia 3.3% (not registered in the
      control group) and microvoltage QRS complex in 11.5% (controls 0.5%, P < 0.001).
      The results of this study confirm that changes in the electrocardiograms of the
      POWs released from Serbian detention camps were far more frequent than in the
      controls.

PMID- 10929235
TI  - Methamphetamine induces an increase in cell size and reorganization of myofibrils
      in cultured adult rat cardiomyocytes.
AB  - To investigate the direct effects of methamphetamine (MAP) on cardiac lesions
      seen in MAP abusers, isolated adult rat ventricular cardiomyocytes (ARCs) were
      exposed to MAP (0.05-1.0 mM) in medium 199 containing 10% fetal calf serum.
      Isolated ARCs attached to laminin-coated substrata and began to spread into
      polygonal shapes with pseudopodia at day 6 in normal culture. However, the cell
      attachment and spreading were inhibited by exposure to MAP (0.5 and 1.0 mM) for
      the first 7 days in culture. On the other hand, exposure to MAP (0.05 and 0.1 mM)
      for 7 days after a 6-day period of normal culture, led to a larger cross surface
      area of cells with more abundant actin bundles compared to control cells (p <
      0.05). This development of spreading area resembled that of norepinephrine
      treated ARCs. In addition, immunoreactive atrial natriuretic peptide (ANP)
      granules developed and accumulated around the nuclear region of ARCs exposed to
      MAP and the number of ANP positive cells tended to increase in a dose-dependent
      manner. These results suggest that chronic exposure to a high concentration of
      MAP may directly inhibit development of ARCs in culture and that a continuous
      exposure to a low concentration of MAP may facilitate the development of cellular
      hypertrophy. Therefore, hypertrophied cardiomyocytes in MAP abusers may be
      provoked by multifactorial incidents of direct and indirect actions of MAP.

PMID- 10929236
TI  - Allele frequencies of 13 short tandem repeats in population samples from the
      Iberian Peninsula and northern Africa.
AB  - The 13 short tandem repeat (STR) loci D3S1358, vWA, FGA, D16S539, TH01, TPOX,
      CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317 and D7S820 as well as the
      amelogenin locus, contained in AmpFlSTR Profiler Plus and/or AmpFlSTR Cofiler
      and/or AmpFlSTR Green I PCR amplification kits, were studied in four populations
      from the Iberian Peninsula, Basques, Catalans, Andalusians and Portuguese and two
      North African populations (Moroccan Arabs and Berbers). The aim of the study was
      to obtain accurate allele frequency data and other genetic parameters of forensic
      interest on the main representative human groups living in Iberia and Morocco
      using an automated method and commercial amplification kits.

PMID- 10929237
TI  - A comparative study on the immunohistochemical detection of early myocardial
      damage.
AB  - The study was undertaken to evaluate the kinetics and distribution patterns of
      several immunohistochemical markers in ischemically and hypoxically damaged
      myocardium. The myocardium of 8 cases of acute myocardial infarction (AMI), 8
      cases of diagnosed acute cardiac death (ACD) and 12 cases of acute exogenic
      hypoxia (AEH) due to CO poisoning or hanging were analysed for depletion of the
      cardiac antigens FABP, troponin C and T, desmin and myoglobin, loss of CD59 and
      deposition of the plasma antigens fibrinogen, fibronectin and the terminal
      complement complex C5b-9. The visualisation of the terminal complement complex
      was positive as early as 30 min after onset of symptoms of AMI. Depletion of
      cellular antigens started earlier than the deposition of plasma antigens. The
      deposition of fibronectin and fibrinogen began earlier than the detection of C5b
      9 but later than the depletion of the cellular antigens. Our findings indicate
      that for the immunohistochemical detection of very early myocardial damage, the
      depletion of myoglobin is at least of the same rank or better than depletion of
      FABP and troponin.

PMID- 10929238
TI  - The role of tumor necrosis factor-alpha in diffuse axonal injury following fluid
      percussive brain injury in rats.
AB  - The immunolocalization of tumor necrosis factor-alpha (TNF alpha) after diffuse
      axonal injury (DAI) is demonstrated using a midline fluid percussion rat model
      (moderate brain injury of 1000 mm Hg was generated) and the effects of TNF alpha
      on the axolemmal permeability using horseradish peroxidase as a tracer. In
      addition, the accumulation of beta-amyloid precursor protein (beta-APP) was
      investigated, which has recently been shown to be a reliable marker for the
      diagnosis of DAI in cases with fatal head injury. TNF alpha levels in brain
      tissues from the impact site and the cortex including the corpus callosum,
      gradually increased during the first 1 h, rose to a maximal elevation at 3 h,
      gradually decreased at 6 h and decreased further at 24 h. Horseradish peroxidase
      (HRP) tracer experiments revealed that primary axonal damage appeared as early as
      15 min after impact but rapidly recovered and that 1 h after impact, secondary
      axonal damage occurred in the corpus callosum and the brain stem. By
      immunoelectron microscopy it was seen that beta-APP accumulated in the axon from
      1 h after impact demonstrating that there was functional axonal damage. TNF alpha
      reactions were detected in the lysosomes of microglia 30 min after impact and 1 h
      after impact these reactions were mainly detected in the glial cells (such as
      microglia, astrocytes and oligodendrocytes) in the corpus callosum and the brain
      stem. It is generally accepted that TNF alpha directly induces primary
      demyelination and oligodendrocyte apoptosis. Therefore, TNF alpha conveyed from
      the microglial cells is one cofactor contributing to the formation of the delayed
      axonal damage observed at these sites. The present study suggests that TNF alpha
      conveyed from the glial cells may contribute to the pathogenic mechanism of DAI
      formation following fluid percussive brain injury.

PMID- 10929239
TI  - Automated solid-phase extraction and two-step derivatisation for simultaneous
      analysis of basic illicit drugs in serum by GC/MS.
AB  - A combination of automated solid-phase extraction (SPE) and subsequent two-step
      derivatisation has been developed for the simultaneous analysis of basic drugs of
      abuse and cocaine metabolites in serum samples. Substances included in this
      procedure are morphine, codeine, methadone, cocaine, benzoylecgonine,
      methylecgonine, amphetamine, methamphetamine, MDMA, MDEA and MDA. SPE with mixed
      mode cartridges (RP-C8 and cation-exchange) was fully automated with a Zymark
      RapidTrace SPE robot. GC/MS analysis was performed after derivatisation with a
      new two-step reaction by trifluoroacetic anhydride and 2,2,3,3,3
      pentafluoropropanol. High recoveries (> 85%) with high reproducibility (CV 1.1
      3.8%) were found for all drugs. High correlation coefficients (r > 0.998) were
      obtained due to the addition of deuterated standards prior to extraction.
      Experience obtained over 2 years of applying this method to drug analysis in
      serum is discussed.

PMID- 10929240
TI  - The application of dental methods of identification to human burn victims in a
      mass disaster.
AB  - This paper deals with the usefulness of dental identification in the case of 28
      human burn victims of a bus accident in Spain. Postmortem forensic procedures for
      identification were used including general external examination, routine
      photographs and radiographs and complementary biological methods. Dental
      identification was also used and a description of the method is presented. Dental
      identification was established in 57% of the cases. When victims were less than
      20 years of age, the success rate of identification by dental methods was higher
      (76% of victims in this age group). The assessment of dental age allowed the
      establishment of identity of four victims. We recommend that dental procedures be
      used in human identification after mass disasters. Odontological and radiographic
      procedures are powerful methods when dealing with burn victims.

PMID- 10929241
TI  - Onset of rigor mortis is earlier in red muscle than in white muscle.
AB  - Rigor mortis is thought to be related to falling ATP levels in muscles
      postmortem. We measured rigor mortis as tension determined isometrically in three
      rat leg muscles in liquid paraffin kept at 37 degrees C or 25 degrees C--two red
      muscles, red gastrocnemius (RG) and soleus (SO) and one white muscle, white
      gastrocnemius (WG). Onset, half and full rigor mortis occurred earlier in RG and
      SO than in WG both at 37 degrees C and at 25 degrees C even though RG and WG were
      portions of the same muscle. This suggests that rigor mortis directly reflects
      the postmortem intramuscular ATP level, which decreases more rapidly in red
      muscle than in white muscle after death. Rigor mortis was more retarded at 25
      degrees C than at 37 degrees C in each type of muscle.

PMID- 10929242
TI  - AgNORs during the process of wound healing. Time dependency as evaluated in vital
      and postmortem biopsy.
AB  - Silver staining of paraffin sections to detect changes in nucleolar organizer
      regions (AgNORs) is an established method for detecting cellular proliferation.
      To determine whether AgNORs are helpful in assessing wound age and vitality, we
      examined intravital and postmortem skin biopsies from rats surviving incised
      wounds to both pinnae for defined intervals up to 384 h using, 7 rats per time
      interval. One biopsy was taken immediately before death, a second 24 h after been
      sacrificed and storage at 8 degrees C. Interactive computer-assisted image
      analysis revealed that in the first 120 h after trauma the total number of
      AgNORs, the mean AgNOR sum area in the nucleus, and the mean AgNOR area per
      nucleus were dependent on survival time. Taken as indicators of proliferative
      activity these morphological phenomena revealed an increase in proliferative
      activity after survival times ranging from 10 to a maximum of 96 h. The findings
      were the same in both intravital and postmortem biopsies. These findings are in
      accordance with those obtained using bromodeoxyuridine. The value of these
      experimental findings in assessing wound age of human beings is discussed.

PMID- 10929243
TI  - Criminal anticipation of DNA investigations resulting in mutilation of a corpse.
AB  - A corpse of a female was found in her apartment in a state of advanced
      putrefaction. Both hands were amputated, the external genitals were excised and
      the body parts had been removed from the scene. The subsequent investigations
      proved that the body parts had been severed post mortem. The cause of death was
      determined to be manual strangulation. A 33-year-old man later confessed that he
      had strangled the victim 9 days prior to discovery of the body and that he had
      had sexual intercourse post mortem. According to the confession, the rational
      motive for the subsequent mutilation was to eliminate biological stains (e.g.
      semen inside the vagina, epithelial cells below the fingernails from scratching)
      suitable for forensic DNA analysis. This constitutes a new type of defensive
      mutilation intended to prevent the identification of the perpetrator. An increase
      in the occurrence would be detrimental to the elucidation rate of homicides: in a
      total of 171 homicides investigated at this institute, DNA analysis of biological
      stains gave reliable evidence in 45 cases.

PMID- 10929244
TI  - DXS10011: a hypervariable tetranucleotide STR polymorphism on the X chromosome.
AB  - The locus DXS10011 is a polymorphic system with a tetranucleotide repeat sequence
      located on the human X chromosome. The distribution of allele frequencies was
      examined in 334 Japanese and 171 German individuals and a total of 36 alleles was
      detected in the two population groups. This STR polymorphism will be a useful
      marker for linkage analysis.

PMID- 10929245
TI  - Evaluation of the ICT malaria Pf test for rapid post-mortem diagnosis of
      Plasmodium falciparum malaria in corpses examined for forensic reasons.
AB  - To test the diagnostic value of a rapid and simple immunochromatographic test
      (ICT) based on the detection of Plasmodium falciparum histidine-rich protein 2
      (PfHRP2) for post-mortem examination, blood samples from 30 consecutive corpses
      were analysed by ICT and Giemsa-stained blood films. Compared to microscopy, ICT
      had 100% sensitivity and 100% specificity even after a considerable time had
      passed between the presumed time of death and testing or after prolonged storage
      of whole blood samples. The ICT yielded positive results for four travellers who
      had returned from Kenya and died from Pl. falciparum malaria. The ICT might
      therefore serve as an additional tool for rapid malaria diagnosis, especially in
      non-endemic countries where experience with microscopic malaria detection is
      limited.

PMID- 10929246
TI  - [Palliative medicine--definitions and principles].

PMID- 10929247
TI  - [Palliative medicine--psychological therapy].

PMID- 10929248
TI  - [Palliative psychooncology--demand and methods. Beginning anew at the end?].

PMID- 10929249
TI  - [Patient consultation and palliative care in neurology, e.g. in amyotrophic
      lateral sclerosis].

PMID- 10929250
TI  - [Pain therapy in palliative medicine].

PMID- 10929251
TI  - [Nutritional therapy in palliative medicine].

PMID- 10929252
TI  - [Active and passive euthanasia from the legal perspective].

PMID- 10929253
TI  - [Vision disorders as a sign of systemic disease].

PMID- 10929254
TI  - [Left-sided thoracic pain in a 56-year old man followed by double vision and
      paresthesias of the left hand].

PMID- 10929255
TI  - [42-year old woman with recurrent diarrhea, increasing dyspnea at rest and
      arthralgia].

PMID- 10929256
TI  - [Low HDL-cholesterol].

PMID- 10929257
TI  - [Pre- and peripartum transmission of hepatitis C virus].

PMID- 10929258
TI  - [Prophylactic drug treatment for renal insufficiency].

PMID- 10929259
TI  - [++UKPDS Study. Metformin in obese patients with Type 2 diabetes (UKPDS 340].

PMID- 10929260
TI  - [Comparison of the circadian variation of the time of onset of acute myocardial
      infarction and of attack of vasospastic angina without significant stenosis].
AB  - OBJECTIVES: To study the involvement of vasospasm as the trigger of acute
      myocardial infarction without significant stenosis, the circadian variation of
      the time of onset of acute myocardial infarction was compared with that of
      vasospastic angina without significant stenosis. METHODS: The subjects consisted
      of 3 groups, 64 patients with acute myocardial infarction without significant
      stenosis, 101 patients with acute myocardial infarction with one vessel disease
      and 98 patients with vasospastic angina without significant stenosis. The times
      of onset of acute myocardial infarction and spontaneous attack of vasospastic
      angina were recorded and classified according to the 4 periods (0:00-6:00, 6:00
      12:00, 12:00-18:00, 18:00-24:00) and the pattern of distribution was compared
      between the 3 groups. RESULTS: The time distribution of acute myocardial
      infarction without significant stenosis showed a double peaked pattern at 6:00
      12:00 and 18:00-24:00 and was similar to the pattern of acute myocardial
      infarction with one vessel disease(p = 0.93). Only a single peak in 0:00-6:00 was
      found in the pattern of distribution of vasospastic angina without significant
      stenosis and differed significantly from acute myocardial infarction(p < 0.01).
      CONCLUSIONS: The circadian variation of the time of onset of acute myocardial
      infarction was similar in patients with or without significant stenosis, and
      differed significantly from that in patients with vasospastic angina.

PMID- 10929261
TI  - Influence of diabetes mellitus on left ventricular function in patients
      undergoing coronary artery bypass grafting.
AB  - OBJECTIVES: Left ventricular function was assessed by two-dimensional
      echocardiography before and one year after coronary artery bypass grafting(CABG)
      in a series of patients with severe coronary artery disease with diabetes
      mellitus(DM) and without DM(non-DM). METHODS: Twenty-three patients with DM and
      50 patients without DM, all with no previous myocardial infarction, underwent two
      dimensional echocardiography before CABG and one year after CABG, in a non
      matched study. For a matched study, 31 patients without DM who had almost the
      same left ventricular function as DM patients at the baseline were selected to
      and compare the rate of improvement in left ventricular function between the DM
      group and the "matched" non-DM group. RESULTS: In the non-matched study, patient
      characteristics were not significantly different between the 2 groups except for
      the incidence of congestive heart failure within one year before CABG, which was
      significantly higher in the DM group. Fractional shortening was significantly
      lower in the DM group at the baseline(p < 0.05) and also one year after CABG(p <
      0.0001). Significant improvement in fractional shortening was seen in the non-DM
      group(p < 0.001), but not in the DM group. The left ventricular end-diastolic
      diameter(LVDd) was significantly larger in the DM group at the baseline(p <
      0.01), and was still significantly larger in the DM group at one year after
      CABG(p < 0.01). No improvement in LVDd was seen in the DM group. In the matched
      study, fractional shortening of the non-DM group also showed significant
      improvement after CABG(p < 0.001). Moreover, the rate of improvement in
      fractional shortening was higher in the non-DM group than in the DM group(p <
      0.05). LVDd tended to be larger in the DM group(p = NS). CONCLUSIONS: Left
      ventricular dysfunction and left ventricular impaired improvement were seen in
      the patients with DM, and CABG improved left ventricular function in the patients
      without DM with poor left ventricular function. These findings indicate that CABG
      therapy may be inadequate for improving left ventricular function in patients
      with DM and severe left ventricular dysfunction at the baseline.

PMID- 10929262
TI  - [Evaluation of coronary flow reserve in patients with vasospastic angina].
AB  - OBJECTIVES: The presence of microvascluar impairment was evaluated in 154
      patients with vasospastic angina identified by the acetylcholine provocation
      test. METHODS: Coronary flow reserve was evaluated with a Doppler flow guidewire
      in 128 vessels of 72 patients with chest pain, but no significant coronary
      stenosis(less than 50% stenosis) and no clinical factors that affect coronary
      flow reserve. Coronary flow reserve was obtained from the ratio of adenosine
      triphosphate-induced maximum/baseline averaged peak velocity. These vessels were
      classified into 2 categories according to whether acetylcholine-induced vasospasm
      was positive or negative. Vasospasm positive was defined as more than 90%
      stenosis provoked with chest pain and/or ischemic ST change. Positive vessels
      were subdivided according to focal or diffuse vasospasm. These vessels were also
      classified into 2 other categories according to whether vasospasm in the distal
      artery was positive or negative. RESULTS: Coronary flow reserve was significantly
      lower in vessels with vasospasm than in vessels without vasospasm in patients
      without vasospasm(2.9 +/- 0.8 vs 3.6 +/- 1.0, p = 0.0005). Coronary flow reserve
      was significantly lower in vessels without vasospasm in patients with vasospasm
      than in vessels without vasospasm in patients without vasospasm(3.0 +/- 0.8 vs
      3.6 +/- 1.0, p = 0.03). There was no significant difference in coronary flow
      reserve between vessels with vasospasm and vessels without vasospasm in patients
      with vasospasm(2.9 +/- 0.8 vs 3.0 +/- 0.8, p = 0.8). There was no significant
      difference in coronary flow reserve between focal and diffuse vasospasm(3.2 +/-
      0.8 vs 2.9 +/- 0.8, p = 0.3). Coronary flow reserve was significantly lower in
      vessels with vasospasm in the distal artery than in vessels without vasospasm in
      the distal artery (2.8 +/- 0.8 vs 3.4 +/- 1.0, p = 0.004). CONCLUSIONS: Patients
      with vasospastic angina have microvascular impairment in both vessels with
      vasospasm, and vessels without vasospasm. Microvascular impairment is prominent
      in vessels with vasospasm in the distal artery.

PMID- 10929263
TI  - [Prediction of cardiac sympathetic nerve activity and cardiac functional outcome
      after treatment in patients with dilated cardiomyopathy: examination using
      dobutamine gated blood pool scintigraphy].
AB  - OBJECTIVES: This study evaluated whether dobutamine gated blood pool scintigraphy
      can predict improvement of cardiac sympathetic nerve activity and cardiac
      function. METHODS: Sixteen patients(10 men and 6 women, mean age 59 +/- 13 years)
      with dilated cardiomyopathy underwent dobutamine gated blood pool scintigraphy to
      measure left ventricular ejection fraction (LVEF) using tracer at 0, 5, 10 and 15
      micrograms/kg/min before treatment. Patients were divided into good responders
      (LVEF increase > or = 15%) 8 patients(GR Group) and poor responders(LVEF increase
      < 15%) 8 patients (PR Group) after treatment with beta-blocker or amiodarone with
      a background treatment of digitalis, diuretics and angiotensin converting enzyme
      inhibitor. I-123 metaiodobenzylguanidine(MIBG) imaging to evaluate cardiac
      sympathetic nerve activity and echocardiography were performed before and at one
      year after treatment. MIBG imaging was obtained 4 hours after tracer injection,
      and the heart/mediastinum count ratio(H/M ratio) calculated from the anterior
      planar image and the total defect score(TDS) from the single photon emission
      computed tomography image. LVEF and left ventricular endo-diastolic dimension
      (LVDd) were measured by echocardiography and New York Heart Association(NYHA)
      functional class was evaluated. RESULTS: The GR Group showed TDS decreased from
      28 +/- 6 to 17 +/- 12(p < 0.05), H/M ratio increased from 1.79 +/- 0.26 to 2.07
      +/- 0.32(p < 0.05), LVEF increased from 29 +/- 8% to 48 +/- 10%(p < 0.01), and
      LVDd decreased from 65 +/- 4 mm to 58 +/- 5 mm(p < 0.05). In contrast, the PR
      Group showed no significant changes in TDS, H/M ratio, LVEF and LVDd. NYHA
      functional class improved in both groups. The improvement was better in the GR
      Group than in the PR Group. CONCLUSIONS: Dobutamine gated blood pool scintigraphy
      is useful to predict the improvement of the cardiac sympathetic nerve activity
      and cardiac function, and symptoms after treatment in patients with dilated
      cardiomyopathy.

PMID- 10929264
TI  - [Recovery of left ventricular function after mitral valve replacement for chronic
      mitral regurgitation: optimal timing of operation according to long-term
      recovery].
AB  - OBJECTIVES: Surgical outcome for mitral regurgitation has significantly improved
      in recent years, so consideration of the optimal operative timing to achieve long
      term quality of life for the patients has become more important. Preoperative
      indices that predict postoperative left ventricular function are very important
      for decision of the operative timing. To reassess the optimal operative timing
      for mitral regurgitation, long-term recovery of the postoperative left
      ventricular function was correlated with preoperative left ventricular end
      systolic volume index(LVESVI). METHODS: One hundred eighty-two patients with
      mitral regurgitation underwent standard mitral valve replacement between January
      1973 and June 1993. The patients were divided into 3 groups according to the
      preoperative LVESVI: Group I (LVESVI > or = 100 ml/m2) included 23 patients,
      Group II (60 < or = LVESVI < 100 ml/m2) 81 patients and Group III (LVESVI < 60
      ml/m2) 78 patients. Two-dimensional echocardiography was performed to measure
      left ventricular diastolic dimension, systolic dimension, fractional shortening,
      end-systolic wall stress and mass index before operation(pre), and 1 month(early)
      and 3 years(late) after the operation. RESULTS: Left ventricular diastolic
      dimension in each group decreased in the early period, but Group I returned to
      the abnormal range in the late period. Left ventricular systolic dimension in
      Groups I and II was at the upper limit of the normal range in the early period
      and returned to the abnormal range in the late period, but Group III remained
      within the normal range throughout the study. Fractional shortening in all groups
      decreased to the abnormal range in the early period, but only Group III returned
      to the normal range in the late period. End-systolic wall stress in Group I
      tended to increase, but Group II had no change, and Group III returned to the
      normal range during the early and late periods. Mass index in Groups I and II
      remained within the abnormal range, but Group III returned to the normal range in
      the late period. CONCLUSIONS: Long-term recovery of the left ventricular function
      in Group I showed a continuous deterioration due to irreversible change of the
      left ventricular myocardium and Group II showed no significant change. In
      contrast, Group III demonstrated a significant improvement after standard mitral
      valve replacement. Patients with preoperative LVESVI of more than 100 ml/m2 have
      already lost the optimal timing for surgical treatment of mitral regurgitation.

PMID- 10929265
TI  - Hypertrophic cardiomyopathy with dominant hypertrophy in the right anterobasal
      region of the ventricular septum: a case report.
AB  - A 62-year-old man was referred to our hospital for investigation of abnormal
      electrocardiography findings. The mean frontal plane QRS axis was directed toward
      the right superior quadrant(-125 degrees). Terminal S waves were present in all 3
      bipolar standard leads and an R wave in lead aVR. RS complex was seen in lead V1
      and deep S waves in leads V2-V6. Left ventricular hypertrophy associated with
      asymmetrical septal hypertrophy was suspected based on transthoracic
      echocardiography, but the echocardiographic quality was poor. Magnetic resonance
      imaging revealed hypertrophic cardiomyopathy with massive wall thickening
      involving the right anterobasal region of the ventricular septum. Magnetic
      resonance imaging may provide useful information about the distribution of
      ventricular myocardial hypertrophy in patients with hypertrophic cardiomyopathy
      and unusual electrocardiography findings.

PMID- 10929266
TI  - [Gamma-interferon-induced cardiomyopathy during treatment of renal cell
      carcinoma: a case report].
AB  - A 78-year-old woman with renal cell carcinoma and pulmonary metastasis presented
      with reversible cardiomyopathy induced by gamma(gamma)-interferon. She was
      treated with gamma-interferon twice a week since November 1996. She presented
      with severe acute congestive heart failure and gamma-interferon was immediately
      discontinued in December 1997. Left ventricular fractional shortening was 38%
      before admission, 12% on admission, and improved to 31% by 40 days after
      discontinuation of interferon together with administration of diuretics and
      angiotensin converting enzyme inhibitor. We restarted the same gamma-interferon
      regimen because it was effective against renal cell carcinoma after 47 days. She
      has remained well with no significant changes of cardiac function or renal cell
      carcinoma for almost one year.

PMID- 10929267
TI  - [Chronic aortic dissection with abnormal shadow in the aortic arch].

PMID- 10929268
TI  - [Mobile mass attached to the mitral valve].

PMID- 10929270
TI  - Auto-antibody tests in peripheral neuropathies: pros and cons.
AB  - Most inflammatory neuropathies, both acute and chronic, probably result from an
      immune attack against antigens of the peripheral nervous system. Specific
      antibodies in serum that react with the peripheral nervous system have been
      described in a number of inflammatory neuropathies. We review the
      pathophysiological significance of auto-antibodies and discuss their use for the
      diagnosis of patients with peripheral neuropathy.

PMID- 10929269
TI  - Semantic dementia: clinical, radiological and pathological perspectives.
AB  - Semantic dementia (SD) is a recently described clinical syndrome characterised by
      an acquired progressive inability to name or comprehend common concepts, with
      little or no distortion of the phonological and syntactic aspects of language,
      and relative sparing of other aspects of cognition, such as episodic memory,
      nonverbal problem-solving, and perceptual and visuo-spatial skills. The cognitive
      locus of this syndrome appears to lie in the permanent store of long-term memory
      representing general world knowledge-semantic memory. The anatomical distribution
      of atrophy is less well-defined, and the contribution of various imaging
      modalities is discussed in the context of a body of 45 published and unpublished
      cases. We conclude that involvement of the left infero-lateral temporal cortex is
      the critical area in the genesis of SD. SD probably always represents a non
      Alzheimer neurodegenerative process; a variety of pathological lesions may be
      present, and possible causes, together with debates about their correct
      classification, are discussed.

PMID- 10929271
TI  - Mortality and cancer incidence in patients with Parkinson's disease.
AB  - To investigate the risks of mortality and cancer incidence in Parkinson's disease
      (PD) we studied the prognosis of 246 PD patients in a community. The cohort of PD
      patients was identified in 1984, and survival, mortality, relocation, and cancer
      incidence during 1984-1992 were examined retrospectively in 1994. The risk was
      measured by a standard effect estimate, i.e., the standardized mortality ratio
      (SMR) or the standardized incidence ratio (SIR), compared with the rates in the
      general population. During the observation period 696 person-years in PD men and
      1018 person-years in PD women were accumulated, and 49 PD men and 53 PD women
      died. The risk of mortality in PD was significantly increased in both sexes (SMR:
      men 1.74, women 1.97). In addition, the risk of cancer incidence was evaluated in
      228 patients aged under 80 years; 8 PD men and 7 PD women developed cancer. The
      risk of overall cancer incidence in PD was less than 1 in either sex, but not
      significantly. The risk of breast cancer in PD women was significantly increased
      (SIR: 5.49), but the 95% confidence interval was wide (1.10-16.03). The results
      indicate that PD patients in a community have a twofold higher risk of mortality,
      and that PD may be associated with an increased risk of breast cancer in women.

PMID- 10929272
TI  - Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized
      controlled clinical trials.
AB  - We conducted a meta-analysis of randomized controlled clinical trials on steroid
      treatment for multiple sclerosis and optic neuritis. Of the 25 trials comparing
      steroids and controls without steroid treatment that we identified 12 were
      selected for this review. A meta-analysis was conducted to calculate the overall
      odds ratio across the studies for the numbers of patients without functional
      improvement and with new relapses. The trials included a total of 1714 patients:
      998 with multiple sclerosis and 716 with optic neuritis. Any type of
      corticosteroids or adrenocorticotropic hormone (ACTH) treatment was considered,
      as was any dosage, route of administration, and length of treatment. Main outcome
      measures were: (a) number of multiple sclerosis patients who did not improve by
      at least one point on the EDSS or equivalent scale, or number of optic neuritis
      patients without complete recovery of visual acuity at 8 or 30 days and at longer
      follow-up; (b) number of multiple sclerosis patients with at least one new
      relapse, or number of optic neuritis patients in whom definite multiple sclerosis
      was diagnosed at longer follow-up. We found that corticosteroids or ACTH produced
      a significant improvement in disability or visual acuity at 30 days (odds ratio
      0.49; 95% CI 0.37-0.64). The improvement was not statistically significant at
      longer follow-up (0.85; 95% CI 0.67-1.09). The treatment did not significantly
      reduce the number of patients with relapses (0.74; 95% CI 0.54-1.01). Both low
      and high doses were effective for 30-day improvement, but only high-dose and
      short-term therapy were factors that identified subgroups with some reduction in
      the risk of new relapse. However, the power of the statistical analysis to detect
      a reliable difference in the subgroups was low. Steroid treatment is therefore
      effective in accelerating short-term recovery in patients with multiple sclerosis
      or optic neuritis. Whether steroids are also effective in reducing the risk of
      relapse, and the optimal dose and length of treatment must still be determined.

PMID- 10929273
TI  - Olanzapine in severe Gilles de la Tourette syndrome: a 52-week double-blind cross
      over study vs. low-dose pimozide.
AB  - We selected four patients with severe Gilles de la Tourette syndrome, high
      frequency of tics (two to ten per minute), vocalizations, and lack of
      comorbidity. These patients (aged 19-40 years) underwent a 52-week double-blind
      cross-over study with olanzapine (5 and 10 mg daily) vs. low-dose pimozide (2 and
      4 mg daily). The reduction in rating scale scores for the syndrome was highly
      significant with 10 mg olanzapine vs. basal and vs. 2 mg pimozide, and was
      significant for 5 mg olanzapine vs. 4 mg pimozide. Only moderate sedation was
      reported by one patient during olanzapine treatment while three complained of
      minor motor side effects and sedation during pimozide treatment. At the end of
      the study all patients opted for olanzapine treatment.

PMID- 10929274
TI  - Familial Kufs' disease presenting as a progressive myoclonic epilepsy.
AB  - Kufs' disease is the adult form of a group of disorders referred to as neuronal
      ceroid-lipofuscinosis or Batten's disease. We report here the clinical and
      anatomopathological features of two young brothers presenting with a progressive
      myoclonic epilepsy corresponding to type A of the disease according to Berkovic.
      The first clinical manifestations occurred before 20 years of age. Diagnosis was
      made in the older brother at autopsy and in the younger brother from a rectal
      biopsy. In addition to characteristic electron microscopic findings, enlarged
      neurons showed strong immunoreactivity against subunit c of mitochondrial ATP
      synthase which has been reported previously in only a few adult cases of neuronal
      ceroid-lipofuscinosis. An extensive review of the published cases underlines the
      rarity of this condition, particularly when onset is early.

PMID- 10929275
TI  - Long-term survival of glioblastoma multiforme: importance of histopathological
      reevaluation.
AB  - The overall prognosis for patients with glioblastoma multiforme is extremely
      poor. However, a small proportion of patients enjoy prolonged survival. This
      study investigated retrospectively the extent to which erroneous
      histopathological classification may contribute to long-term survival of patients
      initially diagnosed with "glioblastoma multiforme." We compared two age- and
      gender-matched patient groups with different postoperative time to tumor
      progression (TTP), defined as "short-term" for TTP of less than 6 months (n =
      54), and "long-term" for TTP of more than 12 months (n = 52). Histological
      specimens of the corresponding tumors, all primarily diagnosed as glioblastoma
      multiforme, were reevaluated according to the current World Health Organization
      (WHO) classification of central nervous system tumors, with the investigators
      being blinded to clinical outcome. Among the tumors from short-term TTP patients,
      one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III)
      while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13
      tumors (25%) from the long-term TTP patients were reclassified, mostly as
      anaplastic oligodendroglioma (WHO grade III; n = 7) or anaplastic
      oligoastrocytoma (WHO grade III, n = 2), respectively. In addition, three were
      reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as
      anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a
      sizable proportion of glioblastoma patients with long-term survival actually
      carry malignant gliomas with oligodendroglial features. The correct
      histopathological recognition of these tumors has not only prognostic but also
      therapeutic implications, since oligodendroglial tumors are more likely to
      respond favorably to chemotherapy.

PMID- 10929276
TI  - Reversible bitemporal hemianopsioa related to iatrogenic intracranial
      hypotension.

PMID- 10929277
TI  - Symptomatic secondary hemorrhagic transformation of ischemic Wallenberg's
      syndrome.

PMID- 10929278
TI  - Extensive brainstem edema in eclampsia: diffusion-weighted MRI may indicate a
      favorable prognosis.

PMID- 10929279
TI  - A pilot study of the relationship between gadolinium-enhancing lesions, gender
      effect and polymorphisms of antioxidant enzymes in multiple sclerosis.

PMID- 10929280
TI  - Cerebrospinal fluid Epstein-Barr virus detection preceding HIV-associated primary
      central nervous system lymphoma by 17 months.

PMID- 10929281
TI  - Cerebral siderosis: deafness by a spinal tumor.

PMID- 10929282
TI  - Incidence of idiopathic intracranial hypertension in Hokkaido, the northernmost
      island of Japan.

PMID- 10929283
TI  - Crossed cerebellar diaschisis and hemiataxia after thalamic hemorrhage.

PMID- 10929284
TI  - Paroxysmal kinesigenic choreoathetosis as a presenting symptom of multiple
      sclerosis.

PMID- 10929285
TI  - Desire Bourneville (1840-1909).

PMID- 10929287
TI  - The oldest known tracks of web-footed birds from the lower Cretaceous of South
      Korea.
AB  - We describe the oldest tracks of web-footed birds from the Early Cretaceous in
      South Korea. The tracks are characterized by a wide divarication angle and a long
      reversed hallux. The web is semipalmate and restricted to the proximal portion of
      the three forward digits. The tracks from the Early Cretaceous in South Korea are
      smaller than those of the Late Cretaceous, therefore confirming the trend of size
      increasing in the early evolution of birds as shown by skeletal fossils. The
      discovery of web-footed tracks with abundant non-web-footed tracks indicates that
      there was a considerable diversification of shore birds as early as the Early
      Cretaceous.

PMID- 10929286
TI  - One- and two-dimensional pulse electron paramagnetic resonance spectroscopy:
      concepts and applications.
AB  - During the last two decades, the possibilities of pulse electron paramagnetic
      resonance (EPR) and pulse electron nuclear double resonance (ENDOR) spectroscopy
      have increased tremendously. While at the beginning of the 1980s pulse-EPR and
      ENDOR applications were still a rarity, the techniques are now very frequently
      applied in chemistry, physics, materials science, biology and mineralogy. This is
      mainly due to the considerable efforts invested in the last few years on
      instrument development and pulse-sequence design. Pulse-EPR spectrometers are now
      commercially available, which enables many research groups to use these
      techniques. In this work, an overview of state-of-the-art pulse EPR and ENDOR
      spectroscopy is given. The rapid expansion of the field, however, does not allow
      us to give an exhaustive record of all the pulse methods introduced so far. After
      a brief and very qualitative description of the basic principles of pulse EPR, we
      discuss some of the experiments in more detail and illustrate the potential of
      the methods with a number of selected applications.

PMID- 10929288
TI  - Touch-free in situ investigation of ancient Egyptian pigments.
AB  - Some of the pigments painted on the Funerary Stele of Amenemhat (ca. 2000 B.C.)
      exhibited at the Egyptian Museum, Cairo and on the walls of the Tomb of Userhat
      (ca. 1420 B.C.), a rock-cut tomb in Thebes, Egypt, were investigated in situ
      using both a convenient home-made hand-held type of X-ray diffractometer and a
      commercial X-ray fluorescence spectrometer in a complementary way under touch
      free conditions. CaCO3.3MgCO3 (huntite) was found in the white-painted parts of
      these two ancient monuments. An arsenic (As)-bearing phase was detected in the
      yellow-painted parts of the latter monument. The occurrence of huntite in Egypt
      has not been reported previously.

PMID- 10929289
TI  - A new find of a Middle Pleistocene mandible from Bilzingsleben, Germany.
AB  - The Middle Pleistocene site at Bilzingsleben is being excavated by the
      Forschungsstelle Bilzingsleben, FSU Jena. It is a living floor with structures of
      settlement and a great number of Lower Palaeolithic cultural remains. So far, 28
      human skull fragments have been discovered, which can be reconstructed into two
      individual skulls. Recently, the right mandible has also been discovered
      (Bilzingsleben E7). Morphological comparisons indicate that there is a great
      similarity to the mandibles of HI and BI of Sinanthropus. A strong likeness to
      Arago II and XIII was also discovered. There are various different archaic
      features which assign the Bilzingsleben mandible and the two skulls to the
      advanced Homo erectus.

PMID- 10929290
TI  - Absence of within-colony kin discrimination: foundresses of the social wasp,
      Polistes carolina, do not prefer their own larvae.
AB  - There is great potential for conflict within social insect colonies especially
      when there are multiple inseminated females laying eggs. One reason that conflict
      is not always realized may be that these females do not identify their own
      progeny and direct their attentions preferentially towards them. Using DNA
      microsatellite loci we were able to determine exactly which female was the mother
      of each larva in eight nests of the social wasp, Polistes carolina. Using 26 h of
      videotapes of natural nests we observed 2,093 feedings of specific larvae by
      these adults and found that they did not preferentially feed their own progeny.
      Instead feedings were distributed to progeny as predicted based on their
      frequency in the nest. The absence of nepotism towards closest kin within
      colonies in this system is likely to promote colony harmony.

PMID- 10929291
TI  - Numerical dating of the Eckfeld maar fossil site, Eifel, Germany: a calibration
      mark for the Eocene time scale.
AB  - Sediments of the Eckfeld maar (Eifel, Germany) bear a well-preserved Eocene fauna
      and flora. Biostratigraphically, Eckfeld corresponds to the Middle Eocene mammal
      reference level MP (Mammals Paleogene) 13 of the ELMA (European Land Mammal Age)
      Geiseltalian. In the maar crater, basalt fragments were drilled, representing
      explosion crater eruption products. By 40Ar/39Ar dating of the basalt, for the
      first time a direct numerical calibration mark for an Eocene European mammal
      locality has been established. The Eckfeld basalt inverse isochron date of 44.3
      +/- 0.4 Ma suggests an age for the Geiseltalian/Robiacian boundary at 44 Ma and,
      together with the 1995 time scale of Berggren et al., a time span ranging from 49
      to 44 Ma for the Geiseltalian and from 44 to 37 Ma for the Robiacian,
      respectively. Additional 40Ar/39Ar dating on a genetically related basalt
      occurrence close to the maar confirms a period of volcanism of ca. 0.6 m.y. in
      the Eckfeld area, matching the oldest Eocene volcanic activity of the Hocheifel
      volcanic field.

PMID- 10929292
TI  - Mycotoxin production on rice, pulses and oilseeds.
AB  - Mycotoxin-producing fungi were isolated from contaminated grains of rice, pulses
      and oilseeds sold in the local markets of Calcutta for human consumption. It was
      found that aflatoxin B1 was produced by Aspergillus flavus and Aspergillus
      parasiticus, aflatoxin G1 by A. flavus, ochratoxin by Aspergillus ochraceous,
      sterigmatocystin by Aspergillus japonicus and citrinin by Penicillium citrinum.
      Aflatoxin B1 (333-10,416 micrograms/kg) was produced by Aspergillus spp. in rice,
      pulses and oilseeds.

PMID- 10929293
TI  - A GPS-based system for recording the flight paths of birds.
AB  - The GPS recorder consists of a GPS receiver board, a logging facility, an
      antenna, a power supply, a DC-DC converter and a casing. Currently, it has a
      weight of 33 g. The recorder works reliably with a sampling rate of 1/s and with
      an operation time of about 3 h, providing time-indexed data on geographic
      positions and ground speed. The data are downloaded when the animal is
      recaptured. Prototypes were tested on homing pigeons. The records of complete
      flight paths with surprising details illustrate the potential of this new method
      that can be used on a variety of medium-sized and large vertebrates.

PMID- 10929294
TI  - Trophallaxis in filled-crop honeybees (Apis mellifera L.): food-loading time
      affects unloading behaviour.
AB  - Honeybees ingested 50% w/w (1.8 M) sucrose solution at a rate feeder offering
      either 16.5, 32.5 or 65 microliters/min. While the time spent ingesting solution
      at the feeder decreased significantly with increasing flow of solution, bees
      attained maximum crop loads with this range of flows. Different parameters
      related to mouth-to-mouth food exchange (trophallaxis) showed important
      modulations as the offered flow of solution was incremented. Trophallactic
      transfer rate, i.e. the speed at which liquid food is transferred from donor to
      recipient bee, was found to increase along with increasing profitability at the
      rate feeder. In the present case, food source profitability could have been
      evaluated by foragers either by measuring the time invested in ingesting the
      solution, or by direct assessment of the flow rate of the feeder. Thus it seems
      that perception of profitability conditions at the food source suffices for later
      representation in the hive through trophallactic contacts, independently of crop
      filling state.

PMID- 10929295
TI  - In vivo measurements of the internal pH of Hediste (Nereis) diversicolor
      (Annelida, Polychaeta) exposed to ambient sulphidic conditions using pH
      microelectrodes.
AB  - The effect of different ambient sulphide concentrations on the internal pH regime
      of Hediste (Nereis) diversicolor was studied under in vivo conditions using
      liquid membrane pH microelectrodes, a method which is new to marine sciences. As
      a case study, the hypothesis was tested whether organisms exposed to ambient
      sulphidic conditions are able to lower their internal pH which, in effect, would
      reduce sulphide influx into the animals and thus could represent an effective
      detoxification mechanism. It was shown that a significant lowering of the
      internal pH occurred within only 20 min after adding sulphide. This pH lowering
      appeared to be dependent on the external sulphide concentration of the ambient
      medium and showed a saturation beyond a threshold level of about 130 microM. It
      is discussed whether this sulphide-induced pH drop is an active regulatory
      mechanism and acts as an effective protection mechanism against sulphide during
      short-term exposures.

PMID- 10929296
TI  - Supratentorial primitive neuroectodermal tumours: diffusion-weighted MRI.
AB  - We report the clinical and pathological findings of supratentorial primitive
      neuroectodermal tumours (PNETs). These are rare, poorly differentiated, highly
      malignant neoplasms occurring primarily in young individuals. They frequently
      show dissemination to the spinal cord and sometimes also beyond neuraxis.
      Preoperative radiological diagnosis is difficult, due to the nonspecific CT and
      MRI characteristics. Our findings indicate that diffusion-weighted imaging (DWI)
      can be used to show the solid portion of the tumour preoperatively and to monitor
      postsurgical recovery. We describe the MRI findings in three patients with
      histologically confirmed supratentorial PNET, focussing on the role of DWI for
      improving the specificity of radiological diagnosis.

PMID- 10929297
TI  - Cystic lesions of the pineal region--MRI and pathology.
AB  - Pineal lesions are rare. Tumours in this location comprise 0.4-1% of intracranial
      tumours. They grow mainly as solid-mass lesions, and cystic tumours are not
      common. On MRI, a cystic configuration is associated usually with non-neoplastic
      pineal lesions rather than with a tumour, but analysis does not allow cystic
      pineal tumours to be distinguished from glial cysts with certainty. We compared
      neuroradiological and pathological data from 13 cystic pineal lesions, analysing
      preoperative MRI. Formalin-fixed, paraffin-embedded surgical specimens were
      stained routinely and immunocytochemically, using the streptavidin-biotin-complex
      method. Histology revealed six pineocytomas, four glial cysts, an arachnoid cyst,
      a low-grade astrocytoma and a teratoma. Signal characteristics of pineocytomas
      were similar in many respects to those of glial pineal cysts. Histomorphological
      analysis allowed unambiguous discrimination between pineocytomas and glial pineal
      cysts.

PMID- 10929298
TI  - MRI in a patient with the Worster-Drought syndrome.
AB  - We describe a patient with the Worster-Drought syndrome (congenital suprabulbar
      paresis), thought to be a failure of development of the corticobulbar tracts. MRI
      showed bilateral perisylvian cortical dysplasia.

PMID- 10929299
TI  - White-matter abnormalities in unirradiated patients cured of primary central
      nervous system lymphoma.
AB  - On MRI, primary brain tumors are commonly seen as contrast-enhancing masses
      surrounded by areas of abnormal signal on T2-weighted images. Following
      successful treatment tumors may no longer show contrast enhancement. The residual
      abnormalities are assumed to be represent "edema" and infiltrating tumor cells.
      We report nine patients with primary lymphoma of the central nervous system who
      had complete responses to intravenous methotrexate, but did not receive
      intrathecal chemotherapy or cranial irradiation. After complete resolution of
      contrast-enhancing lesions, persistent abnormalities on T2-weighted images in the
      region of prior tumor were initially assumed to reflect residual viable tumor. As
      they remained unchanged for years, however, this may not hold true in the cases
      in which primary central nervous system lymphoma responds to chemotherapy alone.

PMID- 10929300
TI  - Atrophy of the corpus callosum correlates with white matter lesions in patients
      with cerebral ischaemia.
AB  - Many studies of white matter high signal (WMHS) on T2-weighted MRI have disclosed
      that it is related to cerebral ischaemia and to brain atrophy. Atrophy of the
      corpus callosum (CC) has also been studied in relation to ischaemia. Our
      objective was to test the hypothesis that CC atrophy could be due to ischaemia.
      We therefore assessed CC, WMHS and brain atrophy in patients with risk factors
      without strokes (the risk factor group) and in those with infarcts (the infarct
      group), to investigate the relationships between these factors. We studied 30
      patients in the infarct group, 14 in the risk factor group, and 29 normal
      subjects. Using axial T1-weighted MRI, cortical atrophy and ventricular
      enlargement (brain atrophy) were visually rated. Using axial T2-weighted MRI,
      WMHS was assessed in three categories: periventricular symmetrical,
      periventricular asymmetrical and subcortical. Using the mid-sagittal T1-weighted
      image, the CC was measured in its anterior, posterior, mid-anterior and mid
      posterior portions. In the normal group, no correlations were noted between
      parameters. In the infarct group, there were significant correlations between CC
      and brain atrophy, and between CC atrophy and WMHS. After removing the effects of
      age, gender and brain atrophy, significant correlations were noted between some
      CC measures and subcortical WMHS. In the risk factor group, there were
      significant correlations between CC and brain atrophy and between CC atrophy and
      WMHS. After allowance for age, gender and brain atrophy, significant correlations
      between some CC measures and periventricular WMHS remained. The hypothesis that
      CC atrophy could be due to cerebral ischaemia was supported by other analyses.
      Namely, for correlations between the extent of infarcts and partial CC atrophy in
      patients with anterior middle cerebral artery (MCA) and with posterior MCA
      infarcts, there were significant correlations between the extent of infarct and
      mid-anterior CC atrophy in the former, and posterior CC atrophy in the latter.
      Our findings could indicate that CC atrophy is associated with cerebral
      ischaemia.

PMID- 10929301
TI  - Klippel-Trenaunay syndrome: frequency of cerebral and cerebellar hemihypertrophy
      on MRI.
AB  - We examined 11 patients, clinically and radiographically diagnosed as having the
      Klippel-Trenaunay syndrome (KTS) by MRI. There were four females and seven males,
      aged 3-51 years (mean 21 years). Two had clear asymmetry of the cerebral and
      cerebellar hemispheres. The thickness of the grey matter was normal, without
      sulcation abnormalities, but the thickness of the white matter was increased; the
      size of the ipsilateral ventricle was normal. These patients had hypertrophy of
      the leg and a cutaneous haemangioma on the same side as the brain abnormality. No
      patient had an intracranial vascular malformation, unilateral megalencephaly,
      cerebral atrophy or hydrocephalus. The prevalence of cerebral hemihypertrophy in
      our series of patients with KTS was thus 18%.

PMID- 10929302
TI  - A quantitative index of intracranial cerebrospinal fluid distribution in normal
      pressure hydrocephalus using an MRI-based processing technique.
AB  - Our purpose was to quantify the intracranial cerebrospinal fluid (CSF) volume
      components using an original MRI-based segmentation technique and to investigate
      whether a CSF volume index is useful for diagnosis of normal pressure
      hydrocephalus (NPH). We studied 59 subjects: 16 patients with NPH, 14 young and
      13 elderly normal volunteers, and 16 patients with cerebrovascular disease.
      Images were acquired on a 1.5-T system, using a 3D-fast asymmetrical spin-echo
      (FASE) method. A region-growing method (RGM) was used to extract the CSF spaces
      from the FASE images. Ventricular volume (VV) and intracranial CSF volume (ICV)
      were measured, and a VV/ICV ratio was calculated. Mean VV and VV/ICV ratio were
      higher in the NPH group than in the other groups, and the differences were
      statistically significant, whereas the mean ICV value in the NPH group was not
      significantly increased. Of the 16 patients in the NPH group, 13 had VV/ICV
      ratios above 30%. In contrast, no subject in the other groups had a VV/ICV ratios
      higher than 30%. We conclude that these CSF volume parameters, especially the
      VV/ICV ratio, are useful for the diagnosis of NPH.

PMID- 10929303
TI  - Focal cortical dysplasia of the temporal lobe with late-onset partial epilepsy:
      serial quantitative MRI.
AB  - We describe serial studies of focal cortical dysplasia causing temporal lobe
      seizures and progressive aphasia in a 54-year-old woman. Initially, MRI volumetry
      of the temporal lobes showed significant left cortical thickening corresponding
      to an elevated amino-acid uptake in the left temporoparietal and inferior frontal
      cortex on SPECT using 3-[123I]iodo-alpha-methyl-L-tyrosine (IMT). After 1 year
      there was severe shrinkage of the left temporal lobe, possibly the result of
      recurrent complex partial seizures.

PMID- 10929304
TI  - Can intravascular lymphomatosis mimic sinus thrombosis? A case report with 8
      months' follow-up and fatal outcome.
AB  - We report a case of intravascular lymphomatosis of the brain with 8 months'
      follow-up and fatal outcome. Several MRI investigations revealed variegated,
      rapidly changing infarct-like lesions and invasion of the walls of the superior
      sagittal sinus and deep veins. When disturbances of the venous outflow are
      detected with multifocal infarct-like lesions, intravascular lymphomatosis should
      be considered in the differential diagnosis. Brain biopsy may ensure the proper
      diagnosis ante mortem, but failure of biopsy is frequent, as in our case.

PMID- 10929305
TI  - MRI of a cerebral cryptococcal granuloma.
AB  - We report a patient with a cerebral cryptococcal granuloma who presented with
      recent memory disturbance and deteriorating mental status followed by temporary
      loss of consciousness. To our knowledge, this is the first report of a cerebral
      cryptococcal granuloma examined by a combination of conventional MRI, fluid
      attenuated inversion recovery and diffusion-weighted imaging and in which the
      surgical specimen was analysed histochemically.

PMID- 10929306
TI  - Diffusion- and perfusion-weighted MRI in a patient with a prolonged reversible
      ischaemic neurological deficit.
AB  - We report acute and follow-up diffusion- and perfusion-weighted MRI (DWI, PWI)
      findings in a patient with a prolonged reversible ischaemic neurological deficit.
      PWI 12 h after the patient was last seen to be without symptoms revealed a large
      perfusion deficit in the left posterior MCA territory with a relatively
      inconspicuous and much smaller abnormality on DWI. Follow-up showed resolution of
      abnormalities on both DWI and PWI, and conventional MRI was normal, apart from a
      very slight abnormality, visible only on FLAIR images, at the centre of the
      initially DWI-positive region. These findings demonstrate the utility of PWI when
      be used in combination with DWI to investigate the pathophysiology of transient
      ischemic syndromes.

PMID- 10929307
TI  - Contrast enhancement of the cerebrospinal fluid on MRI in two cases of
      spirochaetal meningitis.
AB  - We report two patients with meningitis due to spirochaetal infection, both of
      whom showed diffusely enhancing meninges around the brain and spinal cord. In
      addition, there was enhancement of the cerebrospinal fluid after intravenous
      administration of Gd-DTPA.

PMID- 10929308
TI  - Does a herniated nucleus pulposus contribute significantly to a decrease in
      height of the intervertebral disc? Quantitative volumetric MRI.
AB  - A lumbar intervertebral disc with a herniated nucleus pulposus (HNP) often
      exhibits a decrease in the height of the intervertebral space. Our purpose was to
      ascertain whether the loss of volume of an HNP is sufficient to cause a
      perceptible decrease in the height of the intervertebral space. MRI of 44
      patients with 51 HNPs were reviewed. The volumes of the herniated material and of
      the intervertebral discs were calculated for every level from L1-2 to L5-S1. The
      average volume of the HNP was 503 +/- 301 mm3. The average volumes of all 220
      intervertebral discs and of the 127 normal-appearing discs were 14,442 +/- 4200
      mm3 and 17,476 +/- 2885 mm3 respectively. The average volume of the HNP
      represented 3.5% of the parent disc. An average HNP caused a decrease in
      intervertebral space height of 0.35 mm (0.56 pixels). Therefore, the loss of the
      volume of the HNP does not cause a significant decrease in the intervertebral
      space height. The average calculated decrease in the disc height is less than
      that reported in normal diurnal variation.

PMID- 10929309
TI  - Association of intracerebral venous angioma and true arteriovenous malformation:
      a rare, distinct entity.
AB  - We report a mixed cerebrovascular malformation in which a true arteriovenous
      malformation drained into associated venous angiomas. We describe the MRI and
      angiographic appearances and review the literature on mixed vascular
      malformations.

PMID- 10929310
TI  - Two rare lumbar tumours with unusual MRI characteristics.
AB  - We present two rare lumbar lesions with similar MRI features: high signal on T1
      weighted and proton density images and low signal on T2-weighted images; a
      melanotic schwannoma, and a giant-cell tumour-like lesion. Melanin in the first
      case and haemosiderin and metahaemoglobin in the second were responsible for the
      MRI characteristics.

PMID- 10929311
TI  - Bilateral traumatic caroticocavernous fistulae: total resolution following
      unilateral occlusion.
AB  - Balloon occlusion is the accepted treatment for direct posttraumatic
      caroticocavernous fistula. We present a case of bilateral traumatic fistulae
      associated with a pseudoaneurysm. Resolution of both fistulae occurred following
      treatment of one of them by balloon occlusion of the internal carotid artery.
      This case highlights the importance of considering a more conservative approach
      to bilateral fistulae or those associated with a pseudoaneurysm. We review other
      treatment options.

PMID- 10929312
TI  - MRI of orbital schwannomas.
AB  - The literature on MRI of orbital schwannomas is limited. The appearances in three
      patients with an orbital schwannoma were reviewed. A superior orbitotomy through
      a subfrontal craniotomy revealed a schwannoma in all cases. MRI characteristics
      of very low signal on T1-weighted images and homogeneous postcontrast enhancement
      may be helpful for differentiating schwannomas from other intraconal masses.

PMID- 10929313
TI  - What is evolutionary developmental biology?
AB  - All changes in animal form and function during evolution are due to changes in
      their DNA. Such changes determine which proteins are made, and where and when,
      during embryonic development. These proteins thus control the behaviour of the
      cells of the embryo. In evolution, changes in organs usually involve modification
      of the development of existing structures--tinkering with what is already there.
      Good examples are the evolution of the jaws from the pharyngeal arches of jawless
      ancestors, and the incus and stapes of the middle ear from bones originally at
      the joint between upper and lower jaws. However, it is possible that new
      structures could develop, as has been suggested for the digits of the vertebrate
      limb, but the developmental mechanisms would still be similar. It is striking how
      conserved developmental mechanisms are in pattern formation, both with respect to
      the genes involved and the intercellular signals. For example, many systems use
      the same positional information but interpret it differently. One of the ways the
      developmental programmes have been changed is by gene duplication, which allows
      one of the two genes to diverge and take on new functions--Hox genes are an
      example. Another mechanism for change involves the relative growth rates of parts
      of a structure.

PMID- 10929314
TI  - Thoughts on the cerebellum as a model for cerebral cortical development and
      evolution.
AB  - This chapter explores the prospect of using the cerebellar cortex as a model for
      the development and evolution of the cerebral neocortex. At first, this would
      seem a nearly fruitless task given the readily apparent structural and functional
      differences between the two cortices. Cerebellum and cerebrum perform different
      associative tasks, the cellular 'circuit diagram' of the two structures is
      different, even the developmental sequences that give rise to the two structures
      differ markedly. Yet there are similarities between the structures at the
      conceptual level that are difficult to ignore. Both structures have a relatively
      simple modular circuitry and achieve their complexity by an increase in either
      the size or number of the modules. Both have massive commisures connecting the
      left and right halves of the structure. For the cortex this commisure is the
      obvious corpus callosum; the cerebellar commisure is made up of parallel fibres
      of the granule cells that pass freely across the midline. As they are thin and
      unmyelinated, the number of these crossing fibres may well exceed the number of
      the callosal axons by a significant amount. By far the most obvious similarity
      between cortex and cerebellum, however, is that they are both topologically sheet
      like in structure. They are broad and wide in the two-dimensional plane of the
      pial membrane with a relatively modest thickness in the radial dimension. The
      question for this chapter then is whether these similarities, in particular the
      sheet-like organization are coincidental or indicative of larger themes that play
      deeper roles in the development and function of these two seemingly disparate
      brain regions.

PMID- 10929315
TI  - Radial unit hypothesis of neocortical expansion.
AB  - The more than 1000-fold increase in the cortical surface without a comparable
      increase in its thickness during mammalian evolution can be explained in the
      context of the radial unit hypothesis of cortical development. Cortical expansion
      results from changes in the proliferation kinetics of founder cells in the
      ventricular zone that increase the number of radial columnar units without
      significantly changing the number of neurons within each unit. Thus, regulatory
      genes that control the timing (onset/rate/duration) and mode
      (symmetrical/asymmetrical) of cell divisions and the magnitude of programmed cell
      death (apoptosis) in the ventricular zone determine the number of cortical cells
      in a given species. The migration of postmitotic cells and their allocation into
      appropriate positions within the cortex is radially constrained by glial
      scaffolding and thereby creates an expanded cortical plate in the form of a
      sheet. Several families of genes and morphoregulatory molecules that control the
      production, migration and deployment of neurons within the developing cortical
      plate are being identified and their functions tested in vitro and in transgenic
      animals. The results provide a hint of how mutation of genes that regulate the
      early stages of corticogenesis may determine the species-specific size and basic
      organization of the cerebral cortex that sets the stage for the formation of the
      final pattern of its synaptic connections that can be validated through natural
      selection.

PMID- 10929316
TI  - Genetic control of regional identity in the developing vertebrate forebrain.
AB  - In the past we isolated and characterized a number of vertebrate homeobox genes
      expressed in the developing brain. In particular, Emx1 and Emx2 are expressed in
      the developing forebrain of mouse embryos, in a region including the presumptive
      cerebral cortex. In the developing cerebral cortex, Emx1 is expressed in most
      neuroblasts and neurons at all stages of development, whereas Exm2 expression is
      restricted to proliferating neuroblasts of the so-called ventricular zone and to
      Cajal-Retzius cells, but is undetectable in most postmitotic cortical neurons. It
      is conceivable to hypothesize that Emx2 plays a role in the control of
      proliferation of cortical neuroblasts and in the regulation of their subsequent
      migration. This latter process has been recently analysed in some detail in null
      mutant mice. The expression of these and other genes has also been analysed in
      the developing brain of different species of vertebrates. Homologies between
      forebrain subdivisions have been proposed based on the conservation and
      divergence of gene expression patterns.

PMID- 10929317
TI  - Intrinsic and extrinsic control of cortical development.
AB  - Recent advances in the study of cerebral cortical early development are described
      in this chapter. The role of the anterior neural ridge in regulating
      telencephalon induction in the neural plate is discussed, followed by a review of
      the evidence for the roles of ventral, rostral and dorsal patterning centres in
      regulating regionalization of the telencephalon. The patterning centres produce
      secreted molecules (SHH, FGF, BMP, WNT) that regulate the expression of
      transcription factors which control regional identity, cell type specification,
      proliferation and differentiation. These intrinsic patterning mechanisms appear
      to be sufficient to generate much of the regional organization of the cerebral
      cortex present in newborn mice. While intrinsic mechanisms have a major role in
      cortical regionalization and in the production of cortical projection neurons,
      many cortical interneurons are derived from the basal ganglia and then migrate
      into the cerebral cortex. Furthermore, thalamic afferents appear to have an
      important role in maturation of the postnatal rodent cortex. Thus, both intrinsic
      and extrinsic mechanisms control development of the cerebral cortex.

PMID- 10929318
TI  - A hypothesis as to the organization of cerebral cortex in the common amniote
      ancestor of modern reptiles and mammals.
AB  - Opinions on the evolutionary origins of mammalian neocortex have divided into two
      camps: (1) antecedents of the superior neocortex (i.e. occipital, parietal and
      frontal lobes) and temporal neocortex (i.e. temporal lobe) were present in stem
      amniotes, and these antecedent regions gave rise to dorsal cortex and dorsal
      ventricular ridge (DVR), respectively, in living reptiles; (2) the stem amniote
      antecedent of mammalian superior neocortex gave rise to dorsal cortex in the
      reptilian lineage, while the stem amniote antecedent of mammal claustrum,
      endopiriform region and/or basolateral/basomedial amygdala gave rise to DVR in
      reptiles, with mammalian temporal neocortex being a newly evolved structure with
      no reptilian homologue. The latter hypothesis has the merit of being more
      consistent with some current homeobox gene data, but it has the disadvantages of
      positing that mammalian temporal neocortex arose de novo, and of assuming that
      the high similarity between DVR and temporal neocortex in the organization of
      thalamic sensory input and corticostriatal projections and in the topology of
      sensory areas is coincidental. If one assumes that the antecedent of superior and
      temporal neocortex in stem amniotes was one continuous field that histologically
      resembled dorsal cortex in living reptiles, the first hypothesis provides basis
      for a parsimonious account of the origin of superior and temporal neocortex and
      their considerable resemblance to dorsal cortex and DVR in reptiles, as well as
      to Wulst and DVR in birds.

PMID- 10929319
TI  - Evolution of cortical lamination: the reelin/Dab1 pathway.
AB  - The mammalian cortical plate is characterized by its radial organization and its
      inside-outside developmental gradient. Observations on reelin and Dab1-deficient
      mice show that reelin and Dab1 are both required to develop radial cortical
      organization and a normal maturation gradient. In the reptilian cortex, radial
      organization varies among species; it is the most rudimentary in turtles and the
      most elaborate in lizards, and can be described as intermediate in other species
      such as crocodilians and Sphenodon. On the other hand, the gradient of
      corticogenesis is directed from outside to inside in all reptiles studied, as
      well as in mice that are deficient in reelin, Dab1, as well as cyclin-dependent
      kinase 5 (Cdk5) and p35. All reptiles, even turtles, have reelin-expressing cells
      in the embryonic marginal zone. Mammals are characterized by a drastic increase
      in the number of reelin-positive cells (Cajal-Retzius cells) as well as by an
      amplification of reelin expression per cell. In lizards, the pattern of reelin
      expression is different, as reelin-expressing cells are also present below the
      cortical plate. In all mammalian and reptilian species, Dab1 is expressed in
      cortical plate cells. These data suggest that the reelin/Dab1 pathway was a
      driver of cortical evolution on the synapsid lineage and that similarities in
      radial cortical organization between squamates and mammals result from
      evolutionary convergence.

PMID- 10929320
TI  - The contribution of the ganglionic eminence to the neuronal cell types of the
      cerebral cortex.
AB  - The principal neuronal types of the mammalian cerebral cortex are the excitatory
      pyramidal cells and the inhibitory interneurons, the non-pyramidal cells. It is
      thought that these neurons arise in the ventricular zone surrounding the
      telencephalic ventricles. From there, newly generated neurons migrate outward
      along the processes of radial glial cells to reach the cortical plate where they
      accumulate in an 'inside-out' sequence to form the six-layered structure of the
      neocortex. Here we review emerging evidence that pyramidal neurons are generated
      in the cortical ventricular zone, whereas the majority of the non-pyramidal cells
      arise in the ganglionic eminences of the ventral telencephalon. These neurons
      follow tangential migratory routes to reach their positions in the developing
      cortex.

PMID- 10929321
TI  - Conserved developmental algorithms during thalamocortical circuit formation in
      mammals and reptiles.
AB  - The general patterns of early thalamocortical development follow a similar
      sequence in all mammals. Thalamocortical projections descend through the ventral
      thalamus, advance in the internal capsule amongst cells which already possess
      dorsal thalamic projections, then reach the cerebral cortex by associating with
      subplate cells and their early corticofugal projections. Initially, the thalamic
      projections pause in the internal capsule and subplate layer. The interactions of
      the thalamocortical projections with the early generated, largely transient cells
      of the subplate, marginal zone, internal capsule and ventral thalamus are
      believed to play a crucial role in the organized deployment of thalamic
      projections and establishing a functional cortical architecture. Selective
      fasciculation, contact guidance and release of neurotrophic factors are thought
      to play roles in the development of thalamocortical projections. These ideas are
      obtaining support from recent work on reeler and other strains of mice. The
      evolutionary origin of these largely transient cells and the overlying logic of
      early developmental steps are not understood. The behaviour of the
      thalamocortical and corticothalamic projections at the corticostriatal junction
      is particularly puzzling. The comparison of early forebrain development in
      mammals and reptiles is beginning to reveal highly conserved cellular and
      molecular interactions during early thalamocortical development and to reveal
      homologies between telencephalic subdivisions.

PMID- 10929322
TI  - Regionalization of the cerebral cortex: developmental mechanisms and models.
AB  - The cerebral cortex is composed of functionally specialized areas that have
      unique connections with other cortical targets and subcortical nuclei. The
      developmental mechanisms responsible for the formation of discrete regions must
      include the regulation of the expression of genes encoding proteins that control
      axon guidance and targeting. New data on patterns of gene expression demonstrate
      the early appearance of such guidance molecules, thus reflecting the early
      emergence of regional specification within the cortex. Transplant and cell
      culture studies suggest that the decisions made by neuronal progenitor cells to
      express region-appropriate phenotypes is controlled by the capacity of the cells
      to respond to and have access to specific signals. The key to understanding
      cortical specification may lie in determining the factors that control receptor
      diversity on progenitors and the temporal and spatial distribution of inductive
      signals within the forebrain.

PMID- 10929323
TI  - Organizing principles of sensory representations.
AB  - Mammalian brains vary greatly in size and expanse of neocortex. Yet, regardless
      of the extent, much of the cortex consists of orderly representations of receptor
      surfaces. Many of these representations closely reflect the order of their
      receptor sheet. The fidelity of the match can be so exact that discontinuities in
      the receptor sheet, such as the optic disc of the retina or the separations
      between fingers, are reflected in the representations. If parts of the receptor
      surface are duplicated or missing in development, representations are
      appropriately altered. Such isomorphisms suggest that the receptor sheet
      instructs the central representations to influence the course of their
      development. Representations may be fractured into a mosaic of small partial
      maps, possibly as a result of competing factors in development. Parts of receptor
      surfaces can achieve proportionately more than their share of a sensory
      representation. The congruence of borders between representations suggests the
      transfer of instructions across borders. Neural activity patterns are a likely
      source of developmental information in all these instances.

PMID- 10929324
TI  - How does evolution build a complex brain?
AB  - To understand how complex brains evolve one can examine a variety of the products
      of the evolutionary process and then infer the mechanisms that generate the
      differences observed. We address this issue using a number of techniques. We
      combine neurophysiological recording techniques with neuroanatomical tracing
      techniques and histochemical methods in an effort to accurately determine the
      functional subdivisions of the neocortex in a variety of mammals. By using these
      techniques we can determine common features of neocortical organization, or
      common cortical areas, which are considered homologous. We can observe
      modifications to patterns of cortical organization, or to cortical fields
      specifically, that are independently evolved and generally related to
      morphological and behavioural specializations. Comparative studies have led us to
      consider the development of the neocortex and the specific changes in
      developmental mechanisms that might account for the observed changes in extant
      adults. Both comparative studies and developmental studies allow us to formulate
      hypotheses regarding how the neocortex is constructed in the life of an
      individual, and in a lineage over time.

PMID- 10929325
TI  - Developmental plasticity: to preserve the individual or to create a new species?
AB  - The cerebral cortex has an amazing capacity to adjust its organization in
      response to perturbations of its normal development. This developmental
      plasticity can be considered to have, as its ultimate goal, the preservation of
      an 'intact' individual, capable of integrating sensory information to generate an
      adequate behavioural response. The mechanisms underlying developmental
      plasticity, however, can also be considered of importance to generate variability
      among individuals of the same species and, as such, create the platform for
      evolution to occur. Here I describe three experiments that alter the
      configuration of the somatosensory cortex of the mouse. The first is based on the
      removal of whisker follicles neonatally and demonstrates that the formation of
      barrels is dependent of the presence of follicles. The second is based on results
      of selective inbreeding for the number of sensory organs (whisker follicles) and
      illustrates the strong tendency during the period of developmental plasticity to
      preserve the internal organization of the cerebral cortex. The third experiment
      is based on a mutation that affects the formation of barrels and, as a
      consequence, alters cortical processing of sensory information. This mutation can
      be considered to have resulted in an evolutionary deviation.

PMID- 10929326
TI  - The relevance of visual perception to cortical evolution and development.
AB  - The quality of brightness--perhaps the simplest visual attribute we perceive-
      appears to be determined probabilistically. In this empirical conception of the
      perception of light, the stimulus-induced activity of visual cortical neurons
      does not encode the retinal image or the properties of the stimulus per se, but
      associations (percepts) determined by the relative probabilities of the possible
      sources of the stimulus. If this theory is correct, the rationale for the
      prolonged postnatal construction of visual circuitry--and the evolution of this
      visual scheme--is to strengthen and/or create by activity-dependent feedback the
      empirically determined association on which vision depends.

PMID- 10929327
TI  - [Scoliosis: progress in reconstruction of spinal form].

PMID- 10929328
TI  - [Measuring the surface of the back. Value in diagnosis of spinal diseases].
AB  - X-ray study to verify clinical findings in patients with scoliosis and other
      deformities of the spine is associated with considerable radiation exposure as
      well as a variety of other problems, particularly as regards assessing disease
      progression. Hence, in the course of the past few years a number of alternative,
      supplementary spinal diagnostic procedures have been developed which are based on
      analysis of the surface of the back: Moire topography, photogrammetry/raster
      stereometry, opTRImetric system, ISIS system, video raster stereometry
      (formetrics), ultrasound-guided spine analysis (Zebris) and ultrasound topometry.
      To assess the effectiveness of screening, diagnosis, and progression of scoliosis
      the formetric system of video raster stereometry and the Zebris system for
      ultrasound-guided spine analysis were tested. It was shown that the results of
      screening tests, diagnostic study, and progression evaluation of scoliosis and
      sagittal deformities were exact enough using these systems. Furthermore, the
      ultrasound-guided Zebris system offers the option of dynamic analysis of spinal
      movement. Limitations in measurement precision were found in obese patients,
      asymmetric muscle surfaces, and in patients who had undergone surgery, although
      in the latter group progression could be reliably monitored if the radiological
      angle was known. We can assume that surface analysis procedures will gain in
      importance clinically and in practice.

PMID- 10929329
TI  - [2- and 3-dimensional correction of scoliosis by corset treatment. Optimized
      conservative therapy of idiopathic scoliosis with the improved Cheneau corset].
AB  - It is generally accepted that the progression of an idiopathic scoliotic
      deformity with a Cobb angle of between 25 degrees and 40 degrees can be stopped
      by brace treatment alone provided that the generally acknowledged criteria for
      the treatment concerning skeletal growth of the individual are respected. In
      Europe, the Cheneau brace, which was originally designed as an active derotation
      orthosis, is widely in use and is constantly being improved. The biomechanical
      principle of this orthosis consists of a pressure vector that is applied
      laterally (with regard to the 3-point principle) to exert pressure on the peak of
      the curvature in the frontal and transversal planes. Thus, the thoracic, lumbar
      and pelvic body mass that was rotated out of normal body symmetry is transferred
      back to its original position via pressure and derotation. Therefore, an active
      back like the Cheneau orthosis must provide pressure surfaces and sufficient
      expansion spaces. Subtle insights into the actual effect of braces have furthered
      ongoing development to take into consideration the changes to the trunk in the
      sagittal plain and have respected the different states of expansion of the two
      halves of the trunk in the craniocaudal direction. The thoracic flat back and
      cyphosis of the lumbal spine, which were formerly ignored, actually provide a
      real challenge for the technical realization of the brace. The new generation of
      Cheneau braces potentially provides an effective means for the active correction
      of scoliotic spinal deformity in all three dimensions and thus fulfills the
      requirements of modern conservative scoliosis treatment.

PMID- 10929330
TI  - [Criteria for treatment of idiopathic scoliosis between 40 degrees and 50
      degrees. Surgical vs. conservative therapy].
AB  - The treatment of idiopathic scoliosis over 40 degrees (Cobb) during the growth
      period is under discussion concerning the indication for conservative or surgical
      treatment. Curve progression depends on the degree of the frontal and sagittal
      deformity, vertebral rotation, rigidity of the curve, the skeletal age, the age
      and sex of the patient, the familial frequency of scoliosis and the location of
      the curve. In scoliosis over 40 degrees progression is fast and the possibilities
      for successful conservative brace treatment are reduced during the growth period.
      Progression occurs more frequently in thoracic and double major scolioses,
      especially in young patients (Risser sign 0 and 1). Predictive factors of a
      successful brace treatment are the correction of scoliosis and rotation;
      deterioration of both during the brace treatment leads to poor results.
      Evaluating the flexibility of the sagittal profile is important, as is primary
      correction of 30-50% in the brace during the 3 months. Operative correction of
      small primary curves reduces the fusion length, operation time, and blood loss
      and is followed by a reduction in loading on the adjacent vertebral segments in
      comparison to the long fusions necessary in more structural and double major
      scolioses. So far it is not possible to make an equivalent judgment of the
      frequency of the "crankshaft" phenomenon and the treatment necessary in young
      patients (Rissersign 0 and 1) treated by dorsal instrumentation alone, but
      temporary brace treatment may be considered in those cases.

PMID- 10929331
TI  - [Biomechanical principles of ventral and dorsal instrumentation correction in
      scoliosis].
AB  - Scoliosis is a complex deformity of the spine with an abnormal shape in all
      different planes. Purpose of the study is to describe different biomechanical
      aspects of the operative treatment on the basis of own experimental results and
      of a review of the literature. The corrective loads, the resistance of the
      curvature, principles of different implants, the stability of the instrumented
      spine and problems of implant fixation are discussed. Corrective loads are
      divided in forces of distraction, compression, translation and rotation.
      Distraction is more beneficial for severe curvatures (> 50 degrees), while
      transverse load is ideal for milder deformities (< 50 degrees). Compression is
      only efficient when applied segmental and anterior. Resistance increases with
      increasing of the curvature due to the deformation of vertebral bodies. Release
      is possible anteriorly by open technique or endoscopically and posteriorly by
      concave thoracoplasty. Principles of different implants are shown: Harrington-
      (distraction), Luque- (translation), VDS- (compression, rotation), CD- (combined
      loading--posterior) and Kaneda-System (combined loading--anterior). It is
      possible to perform a primary stable fusion of the spine anterior and posterior.
      The stability provided by three anterior devices (VDS, TSRH, CDH) has been
      studied in an in-vitro model. TSRH was found to be significantly (p < 0.05)
      higher in stiffness in flexion/extension and torsion than VDS. In bending there
      was no statistical difference. In all tests CDH was significantly more stable
      than VDS. In flexion/extension it proved higher in stiffness than TSRH, no
      statistical difference was observed in bending and rotation. Bone density plays a
      crucial role in implantfixation, this is more important anterior than posterior.
      Pedicular screws are superior in their fixational strength than lamina hooks and
      screws in the vertebral body.

PMID- 10929332
TI  - [Neuromuscular scoliosis. Follow-up of treatment and therapeutic principles].
AB  - The therapy of neuromuscular scolioses has to be tailored to the needs to the
      individual patient; there are no universally valid schemes of treatment. Detailed
      knowledge of neuromuscular diseases and their course is essential. For this
      reason, an interdisciplinary team is desirable; only in this way can all medical
      and surgical aspects of the underlying disease--which interfere with the therapy
      of the scoliosis--be treated successfully. The continual improvement in medical
      treatment of neuromuscular disease in recent decades has led to a significant
      increase in life expectancy. In addition, the severe consequences of failure to
      treat spinal deformities have become clear. Neglect or inadequate treatment of
      neuromuscular scolioses can have dramatic consequences, including inability to
      sit and serious impairment of cardiorespiratory status. The goal of treatment is
      therefore to prevent the spinal deformities leading to a dangerous worsening of
      respiratory status. Moreover, the therapy should improve function, which in most
      cases means restoring a stable sitting position. From the mechanical viewpoint
      this means restoration of spinal balance with a vertical spinal axis at right
      angles to a horizontal pelvis.

PMID- 10929333
TI  - [Treatment of scoliosis and scoliokyphosis in Recklinghausen neurofibromatosis].
AB  - Spine deformities are a frequent symptom of neurofibromatosis Recklinghausen.
      Especially NF1 shows next to numerous alterations in the skeleton in some cases
      massive scoliosis and kyphosis. There are different theories for the development
      of the spine deformities, one of them is that specific alterations of the
      vertebra are caused by an elevated intraspinal pressure on the osteoporotic bone.
      A classification from a clinical point of view discriminates 3 types of severity.
      Type 1 shows instead of the in x-rays inconspicuous findings
      neurofibromatosistypical alterations in other diagnostic procedures (e.g. MRI).
      Extreme variations like short curved scoliokyphosis with massive destruction and
      severe spine imbalance are described as type 3. Operative treatment is dependent
      on the severity of the deformity. Intraspinal tumors have to be removed. Because
      of the elevated neurological risk the proceeding has to be very careful,
      sometimes there is a temporary Halo-extension necessary. Anterior substance
      defects are filled with bone or cages. The posterior instrumentation (in most of
      the cases a 2-rod-stabilization) is performed by transpedicular screws.
      Frequently there is a concave chest wall plastic (CTP) indicated. To prevent
      neurological complications early surgical procedure is sometimes necessary.
      Complications can be reduced by careful proceeding, exact preoperative diagnostic
      and classification. But next to operative experience a qualified
      anaesthesiological and intensive care units are absolutely necessary.

PMID- 10929334
TI  - [Minimally invasive ventral release and endoscopic ventral instrumentation in
      scoliosis].
AB  - We report on three years of experience with a new method of a simultaneous
      endoscopically assisted anterior release in the prone position, combined with
      transpedicular posterior scoliosis correction and fixation. In 60 cases this
      simultaneous approach yielded substantial advantages. True derotation of the apex
      -even in the thoracic spine--is achieved. Because of resection of apical discs,
      the hypokyphosis can be corrected easily. Apical derotation, restoration of the
      kypotic profile and more effective correction of lateral translation add up to
      true three-dimensional correction of scoliosis. The disadvantages of insufficient
      anterior anchorage of fixation implants are avoided, since correction and
      fixation are achieved posteriorly. An additional advantage of this combined
      approach and the use of pedicular screws is the fact that in idiopathic scoliosis
      fusion that is no longer than from end- to end-vertebrae is sufficient. Thus, in
      most King II curves the thoracolumbar junction does not need to be fused.

PMID- 10929335
TI  - [Ventral and dorsal correcting and stabilizing methods in idiopathic scoliosis.
      Long-term outcome].
AB  - The age of standardized instrumented scoliosis correction and stabilization began
      with Harrington instrumentation (HI). With HI, satisfactory long-term correction
      of the frontal plane averaged approximately 50%, but without notable derotational
      capabilities. The distraction of the concavity leads to reduction of the sagittal
      contour of the spine (flat back), which is biomechanically disadvantageous. The
      newer multisegmentally attached implant systems avoid this disadvantage. The
      first prototypes of these systems were Luque- (SSI) Cotrel-Dubousset
      instrumentation. Ideal indications for posterior instrumented curve correction
      are structural idiopathic double major curves and flexible single curves.
      However, even with these newer doublerod systems derotation is low, because
      derotation is, without any doubt, related to anterior release and thus decoupling
      of the segments by means of disc resection. The optimum method of correction and
      stabilization of scoliosis using the anterior approach is the ventral derotation
      spondylodesis (VDS), according to Zielke, who considers it to be a major
      improvement over Dwyer instrumentation. VDS is the first implant system with
      which true three-dimensional, segmental curve correction was made possible. Long
      term correction of the frontal plane and derotation averages approximately 70%
      and 50%, respectively. Ideal indications are single lumbar, thoracolumbar and
      thoracic curves. In our experience, the so-called kyphogenic effect of VDS due to
      anterior convex compression, can be counteracted by derotation and preserving
      disc space height with weight bearing bone grafts or cages. The low internal
      stabilizing capabilities with the risk of rod fracture and pseudarthrosis are
      unfavorable. They make long term cast or brace treatment necessary
      postoperatively. Meanwhile, the disadvantage of the low internal stabilizing
      capabilities of VDS has been overcome with the development of the primary stable
      Halm-Zielke instrumentation and other primary stable anterior fixation systems.

PMID- 10929336
TI  - [Halm-Zielke instrumentation as primary stable improvement of the Zielke-VDS in
      idiopathic scoliosis. 1 to 4 year outcome of a prospective study of 29
      consecutive patients].
AB  - Halm-Zielke Instrumentation (HZI) was developed to eliminate the disadvantage of
      ventral derotation spondylodesis (VDS)-Zielke in terms of lack of primary
      stability and in order to simplify sagittal plane control. Within a prospective
      clinical trial started in 1993, we have studied whether HZI fulfills these
      demands. HZI is an anterior double-rod system with a two screw per vertebral body
      fixation. The longitudinal components consist of a threaded VDS rod and a solid
      rod, which are attached to a hinge-conducted lid plate. Twenty-nine consecutive
      patients with idiopathic scoliosis and curves ranging from 36 degrees to 92
      degrees were treated with HZI. The follow-up period ranged from 1 to 4 years.
      Correction of the frontal plane within the instrumented levels averaged 71.6% and
      70.5% postoperatively and at follow-up, respectively. Derotation averaged 53.7%
      and mean correction of the tilt of the lowest instrumented vertebra was 69.5% at
      final follow-up. Thoracolumbar kyphosis was present in eight patients and was
      always completely corrected from +18.8 degrees to 3.3 degrees on average. One
      implant-related complication involved a screw breakage 18 months postoperatively
      without adverse effects. There was no case of pseudoarthrosis. All patients were
      mobilized without any additional external immobilization in terms of a brace or
      cast, and were allowed to go swimming for physiotherapeutical purposes
      immediately after wound healing. This study proves that HZI is a primary stable
      implant to perform VDS. Implant-related disadvantages typical of VDS are
      eliminated. Thereby, the period of rehabilitation is shortened by many months due
      to avoidance of cast and brace treatment.

PMID- 10929337
TI  - [Ventrodorsal correction and instrumentation in idiopathic scoliosis].
AB  - A number of different procedures are used for the surgical treatment of King II
      scoliosis. One reason for the controversial discussion in this context is that
      the term King II scoliosis is usually inadequate, because there are partly marked
      clinical and radiological differences in this type of curvature. From January
      1996 to December 1997, a total of 26 patients with rigid King II scoliosis were
      submitted to a ventrodorsal procedure. Twenty-three patients were included in the
      study. The indication for this procedure was established in cases with a
      secondary lumbar curvature of at least 50 degrees as well as unsatisfactory
      straightening of the primary and secondary curvature in the bendings and
      inadequate horizontal positioning of the caudal end vertebra of not less than 10
      degrees. Ventral Derotation-Spondylodesis (VDS) and Dorsal correction
      Spondylodesis (DKS) led to a thoracic and lumbar straightening from 68.4 degrees
      to 13.2 degrees and from 61.4 degrees to 17.8 degrees, respectively. The tilt of
      the vertebra instrumented farthest caudally was corrected from 21.2 degrees to
      4.9 degrees. The thoracic hypokyphosis was improved from 16.6 degrees to 25.1
      degrees. In 11 patients, the dorsal instrumentation was extended to the caudal
      end vertebra, in another 11 patients, instrumentation was achieved up to a
      vertebra cranial from the end vertebra. The correction loss and complication rate
      was extremely low. Based on the surgical goals discussed further down, combined
      application of VDS and DKS is efficient and suitable in conjunction with the
      indication described. The complication rate is quite low. The different types of
      King II scoliosis have to be differentiated preoperatively.

PMID- 10929338
TI  - [Cemented hip prosthesis implantation--decreasing the rate of fat embolism with
      pulsed pressure lavage].
AB  - Intraoperative fat embolism associated with cemented total hip arthroplasty is a
      well recognized complication. In a new sheep model allowing for standardized
      bilateral, simultaneous cement pressurization we studied the effectiveness of
      both pulsatile and syringe lavage of equal volume with regard to their cleansing
      capabilities as measured by fat and bone marrow intravasation. The operative
      procedure involved bilateral placement of intravenous catheters into the external
      iliac veins via retroperitoneal approach. After femoral neck osteotomies both
      femoral cavities were prepared for retrograde cement application. After
      randomization one side was lavaged with 250 ml irrigation using a bladder
      syringe, the contralateral femur with the identical volume but using a pulsatile
      lavage. A specially designed apparatus was used to allow for bilateral
      simultaneous cement pressurization. Venous blood from both iliac catheters was
      then collected, anticoagulated and a quantitative and qualitative fat analysis
      was performed. Despite equal volume manual lavage produced significantly higher
      fat and bone marrow intravasation (P < 0.001) than pulsatile lavage thus
      suggesting that not only the volume but also the quality of bone lavage is an
      essential factor influencing the risk of fat embolism and adverse
      cardiorespiratory effects. Our findings further emphasize the important role of
      pulsatile lavage in preventing fat and bone marrow embolisation during cemented
      total hip arthroplasty.

PMID- 10929339
TI  - [Finger tip defect injuries].

PMID- 10929340
TI  - [A homeopathic drug is equivalent to diclofenac?!].

PMID- 10929341
TI  - [Knee endoprosthesis: finding the optimal implant for every indication].

PMID- 10929342
TI  - The shapes and relative movements of the femur and tibia at the knee.
AB  - Unlike the situation at the hip, controversy continues as to the shape of the
      bones in the knee (for example, are the femoral condyles helical in sagittal
      section?) and as to the way in which the femur moves on the tibia (for example,
      does the femur roll-back during flexion?). Although the replaced knee is unlikely
      to achieve normal kinematics, it seems desirable to understand how far it departs
      from normal. A knowledge of the normal is also important in the management of
      ligament injuries. Thus it is desirable to resolve these controversies. We have
      studied the shape of the bones and the way in which they move in the normal
      cadaveric knee using MRI as a first step to developing an MRI protocol for
      establishing the kinematic behaviour of the knee in the clinical setting. Our
      results have been confirmed in normal volunteers using Open Access and
      Interventional MRI. The latter enables the knee to be imaged whilst the subject
      is weight-bearing.

PMID- 10929343
TI  - Unicompartmental arthroplasty. Results in Sweden 1986-1995.
AB  - Since 1975 the Swedish Knee Register founded by the Swedish Orthopaedic society
      records primary knee arthroplasties and their revisions to evaluate indications,
      type of implants, revision rates etc. In the following, the results of
      unicompartmental arthroplasties (UKAs) are described. In osteoarthrosis UKAs have
      higher revision rates than total knee arthroplasties (TKAs), but a lower risk of
      serious complications and infections. Patients with medial UKA were as satisfied
      as patients with TKA. Furthermore, UKA is considerably cheaper than TKA.
      Therefore the use of an UKA seems to be a good alternative in appropriate
      patients.

PMID- 10929344
TI  - Is the St. Georg Sled better than total knee replacement?
AB  - In Bristol the St Georg Sled prosthesis has been in continuous use for 25 years
      and we remain committed to it. During this time many trials demonstrating its
      effectiveness have been carried out.

PMID- 10929345
TI  - [Metal-backed sled endoprostheses. Indications and results].

PMID- 10929346
TI  - [Follow-up of a personal series of sled endoprostheses after 8-11 years. Analysis
      prosthesis failures, presentation of possible revisions].

PMID- 10929347
TI  - [Complete superficial total endoprosthetic replacement of the knee. Differential
      indications].

PMID- 10929348
TI  - [Superficial knee joint replacement in rheumatoid arthritis. Differential
      indications with reference to biomechanical aspects].

PMID- 10929349
TI  - [10 years experience with the PFC knee endoprosthesis].

PMID- 10929350
TI  - The TACK knee prosthesis. Analysis of a uniform case series.
AB  - We implanted the total arthroplasty knee or TACK prosthesis in 40 patients with
      degenerative osteoarthritis. We used the same surgical technique in all patients.
      Full extension and flexion more than 90 degrees were achieved in all 40 knees.
      All patients obtained a HSS score of more than 88 points. The results confirm
      that the TACK prosthesis provides excellent results in patients with degenerative
      osteoarthritis if there is no significant bone loss, serious ligament laxity or
      extensive deformation.

PMID- 10929352
TI  - Rotating knee prosthesis. Surface or hinge replacement?
AB  - Until the early 1990's our experience in Total Knee Replacement (TKR) was based
      on AGC 2000, Tricon M and MG implants. Starting from 1992 we decided to use a
      rotating knee prosthesis. At that time in Italy there were many knee replacement
      devices with rotating elements: Oxford, LCS, Rotaglide and Endomodel from Link.
      The Endomodel rotating prosthesis was our choice and between 1992 and 1995 we
      implanted 142 prosthesis of this type, 128 as primary replacement and 14 as TKR
      revision. The overall results were good or excellent in most of our cases (Fig.
      1). During this period we had 6 dislocations of the device (Fig. 2) and 4
      infections: 1 from our service and 3 coming from other hospitals.

PMID- 10929351
TI  - [ENDO model rotation knee prosthesis. Guided superficial replacement with stem].

PMID- 10929353
TI  - Total knee arthroplasty in femorotibial instability.
AB  - Regarding the reasons for failure of conventional knee arthroplasty a lot of work
      has be done on loosening and polyethylene wear, often leading to recurrent
      deformation and osteolysis. But there are only few reports concerning
      femorotibial instability. This instability is related to failure of the
      collateral ligaments which can often be found in cases of important frontal
      deformity both in the varus and valgus knee or in rheumatoid arthritis.
      Femorotibial instability has been reported in the literature as reason of failure
      of knee replacement in 10 to 30% of all cases. This complication may be avoided
      by a precise preoperative analysis including unipodal standing view and stress X
      Rays. Encouraged by the good long-term results published by the Endo-Klinik we
      started to use the ENDO-Model rotational knee system in patients with suspected
      femorotibial instability in order to resolve the problems of resurfacing the
      patella restoring mobility correcting the deformity stabilising the knee In fact,
      the rotating or hinge prosthesis is actually transforming the anatomical joint in
      a mechanical joint in which the pivot is acting as a ligament should act.

PMID- 10929354
TI  - [Total knee joint rotational endoprostheses. Indications and long-term follow
      up].

PMID- 10929355
TI  - [Starr coupled knee endoprostheses as revision implants].

PMID- 10929356
TI  - [Hinged knee joint endoprosthesis. Special indications].

PMID- 10929357
TI  - [Mutars--a modular tumor- and revision system. Experiences at the Munster Tumor
      Center].

PMID- 10929358
TI  - [Endo-Model hinged prosthesis--a model with a future? Experiences and outcome
      after 20 years use].

PMID- 10929359
TI  - Connatal Pelizaeus-Merzbacher disease in two girls.
AB  - We report the clinical, radiological and electrophysiological signs in two
      unrelated girls with the connatal form of Pelizaeus-Merzbacher disease (PMD). MRI
      plays an important role in the diagnosis, demonstrating the virtual absence of
      myelination. PMD is classically described as an X-linked leukodystrophy. Our two
      cases reinforce the hypothesis of a possible autosomal recessive transmission of
      the connatal form of PMD in some families, as recently presented.

PMID- 10929360
TI  - Reliability of cranial CT versus intracerebral pressure measurement for the
      evaluation of generalised cerebral oedema in children.
AB  - OBJECTIVE: To examine the extent to which intracranial pressure (ICP) in children
      after severe brain trauma can be determined by cranial CT. MATERIALS AND METHODS:
      Two experienced paediatric radiologists, without any knowledge of the clinical
      symptoms, evaluated 124 CT scans from 65 children (average age 5.4 years) who
      underwent intracranial measurement of their cerebral pressure. RESULTS: CT had
      high sensitivity (99.1%) for 'high cerebral pressure' but a much lower
      specificity (78.1%). The examiners tended to estimate ICP as 'high' even when
      actual ICP was low. Since therapy for lowering cerebral pressure involves
      potential risks, actual cerebral pressure measurement, particularly in children,
      should be considered before intervention (e.g. hyperventilation or trepanation).
      We report the change in different intracerebral fluid compartments with varying
      cerebral pressure and modifications of the density of the brain tissue in an
      inter- and intraobserver comparison. CONCLUSION: The radiologist cannot
      differentiate, for methodological reasons, between a change in the intracranial
      fluid compartments not associated with a change in ICP and one in which it is
      critically elevated. Before any interventional treatments such as decompression
      trepanation or hyperventilation are instituted, measurement of ICP should be
      considered, especially in children.

PMID- 10929361
TI  - Prospective assessment of pituitary size and shape on MR imaging after
      suppressive hormonal therapy in central precocious puberty.
AB  - OBJECTIVE: The diagnostic significance of an enlarged pituitary gland regarding
      both shape and size parameters on MR imaging has previously been demonstrated in
      children with central precocious puberty. This study was designed to assess
      changes in these parameters following successful suppressive therapy of central
      precocious puberty with the gonadotropin-releasing hormone (GnRH) analogue.
      MATERIALS AND METHODS: Twelve girls (mean age 7.3 years) with central precocious
      puberty were prospectively enrolled in our study protocol. Sagittal and coronal
      MR images of the pituitary region were obtained in all patients before treatment
      and after at least 6 months of GnRH analogue therapy (mean 18.0 months).
      Parameters measured included pituitary gland height, length, width, sagittal
      cross-sectional area, and volume. RESULTS: All patients had excellent clinical
      response to treatment with arrest of secondary sexual development, normalization
      of serum estradiol levels, and complete obliteration of the LH response to
      diagnostic GnRH stimulation. No significant change occurred in any pituitary size
      or shape parameter following GnRH analogue therapy. CONCLUSION: Favorable
      clinical response to GnRH analogue therapy in central precocious puberty is not
      accompanied by significant a change in pituitary gland size and shape.

PMID- 10929362
TI  - Surveillance imaging in children with medulloblastoma (posterior fossa PNET).
AB  - BACKGROUND: The use of surveillance imaging in children with medulloblastoma has
      been criticised. The aim of this study was to determine what proportion of
      relapses are detected by surveillance and whether these are found at a relatively
      favourable stage. METHODS: This study was a retrospective review of the medical
      charts and imaging studies of 89 patients treated at a single children's cancer
      centre. Relapse was defined as evidence of an increase in volume of residual
      tumour of greater than 25% or the presence of metastases, or new onset of
      positive CSF cytology. Relapse was termed symptomatic if it was diagnosed by
      tests performed because of new symptoms that occurred in the interval between
      surveillance examinations. Asymptomatic relapse was diagnosed solely on the basis
      of surveillance imaging. Survival time to relapse was calculated from the date of
      the first surgical procedure. RESULTS: Surveillance imaging detected 17 (71%) of
      the 24 relapses that occurred later than 6 months after diagnosis. All seven
      patients who presented with symptoms between scans have died, with a median
      survival from relapse of 5 months. Median survival from relapse in the patients
      detected by surveillance was 44 months, and four remain alive at 44-75 months.
      The patients detected by surveillance tended to have less advanced disease, which
      was more amenable to salvage therapy. CONCLUSION: This type of study cannot prove
      that surveillance imaging improves survival in children with medulloblastoma
      because of the effects of lead time and length biases. Despite this, surveillance
      does appear to be effective in detecting potentially curable medulloblastoma
      relapses and should be offered to all patients.

PMID- 10929363
TI  - Myositis ossificans traumatica in young children: report of three cases and
      review of the literature.
AB  - Myositis ossificans traumatica (MOT) is a rare musculoskeletal disorder in young
      children. Clinical and imaging presentation in the early stage of disease makes
      it difficult to differentiate between infection and musculoskeletal neoplasms,
      particularly in the absence of a history of trauma. Three cases of MOT in
      children under the age of 10 years, two with inferential trauma, are presented
      and the findings on different imaging modalities are discussed with reference to
      the existing literature. While findings based on a single imaging technique,
      including MRI, may be rather non-specific and even misleading, the combination of
      different modalities can assist in the consideration of MOT as a possible
      diagnosis. For example, the demonstration of soft-tissue haematoma on US would
      suggest the traumatic origin. A rational imaging approach is proposed.

PMID- 10929364
TI  - Schmid type metaphyseal chondrodysplasia: a spondylometaphyseal dysplasia
      identical to the "Japanese" type.
AB  - BACKGROUND: Schmid-type metaphyseal chondrodysplasia (Schmid MCD) is an autosomal
      dominant chondrodysplasia resulting from various mutations in the COL10A1 gene.
      This disorder has been well delineated at a clinical level and has been
      classified radiographically as a pure metaphyseal chondrodysplasia. A missense
      mutation in the COL10A1 gene has also been shown to cause a rare spondylo
      metaphyseal chondrodysplasia (SMD) named the "Japanese" type which, apart from
      exhibiting a mild spinal phenotype, shares striking clinical and radiographic
      similarities to Schmid MCD. OBJECTIVE: The clinical, radiographic and molecular
      similarities between Schmid MCD and Japanese SMD led to the hypothesis that these
      conditions could be identical type X collagenopathies. MATERIALS AND METHODS: We
      analyzed 33 cases of typical Schmid MCD from the International Skeletal Dysplasia
      Registry, looking specifically for any radiographic evidence of spinal
      involvement. RESULTS: We found that in 9.1% (3/33) of cases reviewed there was
      definite radiographic evidence of spinal involvement comprising mild
      platyspondyly, vertebral body abnormalities, and end-plate irregularity.
      CONCLUSION: These data indicate that spinal changes are an uncommon but variable
      component of Schmid MCD and that this condition and "Japanese" SMD are identical
      collagen type X disorders. Furthermore, the fact that the specific mutation
      reported in the family with Japanese type SMD, resulting in the substitution of a
      glutamic acid residue for a glycine at codon 595 (G595 E), has also been reported
      in a patient with Schmid MCD strongly supports this conclusion.

PMID- 10929365
TI  - Correction of odontoid dysplasia following bone-marrow transplantation and
      engraftment (in Hurler syndrome MPS 1H).
AB  - BACKGROUND: Odontoid dysplasia is recognized as a major component of the
      constellation of dysostosis multiplex lesions associated with Hurler's syndrome
      (MPS 1H). Because of this abnormality, there is an increased risk of atlantoaxial
      subluxation with potential cervical spinal cord injury. A significant alteration
      of the natural history of the disease with respect to the visceral, cardiac, and
      skeletal systems has resulted in an increased life span for MPS 1H patients
      associated with engraftment from normal donors. OBJECTIVE: The purpose of this
      study was to evaluate the longitudinal changes of odontoid dysplasia in MPS 1H
      following engraftment from bone-marrow transplantation (BMT). MATERIALS AND
      METHODS: A retrospective review of sequential plain film or cervical spine MR was
      performed in patients with MPS 1H. Odontoid morphology was graded as aplasia,
      severe dysplasia, moderate dysplasia, mild dysplasia, or normal. Odontoid
      morphology was plotted against the time interval. Fully engrafted,
      nontransplanted, and partially engrafted patients had careful imaging evaluation
      of the odontoid process. RESULTS: Ten patients were studied with a mean interval
      follow-up of 8.7 years post-BMT. Seven patients were totally engrafted. Two
      patients were nontransplanted, and one patient had only partial engraftment (20%
      enzyme activity). All totally engrafted patients had a progressive improvement in
      the grade of odontoid dysplasia following BMT. Patients with partial engraftment
      or without transplantation demonstrated static or increasing odontoid dysplasia.
      MR imaging showed abnormal dural soft-tissue masses at the level of C2 in all
      patients. Reduction in the grade of odontoid dysplasia was not associated with
      significant change in the appearance of the upper cervical soft-tissue masses.
      CONCLUSION: For the first time, this report documents that patients with MPS 1H
      show a decrease in the degree of odontoid dysplasia on imaging after successful
      engraftment following BMT.

PMID- 10929366
TI  - Traumatic diaphragmatic injuries in infants and children: imaging findings.
AB  - OBJECTIVES: Traumatic diaphragmatic injuries (DI) in infants and children are
      uncommon and are often associated with multiple severe injuries. Delayed
      presentation can be life threatening due to organ herniation and strangulation.
      We present the imaging findings in a relatively large population of children who
      experienced this rare injury. METHODS: Medical records of all patients admitted
      to our Trauma Service from 1977 to 1998 with DI were retrospectively reviewed
      recording imaging, clinical and surgical or autopsy findings. RESULTS: Of sixteen
      patients with DI (7 females, 9 males; age 3 weeks to 15 years), 14 suffered from
      blunt trauma secondary to high-energy impact, and 2 from penetrating injuries.
      Unilateral DI occurred equally on each side, with one bilateral injury.
      Associated injuries, present in 81%, included severe head injuries, visceral,
      mesenteric and vascular injuries and multiple fractures. Six patients died from
      multiple organ failure (3), head injury (2), and shock (1). Findings in the
      initial chest X-ray suggested the diagnosis in 13 (81%) of 16 injuries, and CT
      demonstrated irregularity and thickening of the diaphragm in 4 out of 7.
      CONCLUSIONS: Plain film findings suggested the diagnosis in most; CT and MR were
      useful adjuncts. High index of suspicion and awareness of the mechanism of injury
      can lead to prompt diagnosis, early repair, and decreased morbidity and
      mortality.

PMID- 10929367
TI  - Abdominopelvic lipomatosis in a child with indefinite physical findings.

PMID- 10929368
TI  - Liver biopsy methods for pediatric oncology patients.
AB  - BACKGROUND: Liver biopsy is a high-risk procedure in oncology patients, and
      optimal methods for children have not been established. OBJECTIVE: To assess the
      effectiveness and safety of two methods of performing liver biopsy in pediatric
      oncology patients. MATERIALS AND METHODS: Between May 1997 and July 1999, 51
      liver biopsies (22 percutaneous and 29 transjugular) were performed. The 22
      percutaneous biopsies (13 focal hepatic lesions and 9 general liver biopsies)
      were performed under sonographic guidance; 21 used a spring-loaded needle
      (usually 18 G). In 21 patients, a coaxial sheath was used to inject a slurry of
      microfibrillar collagen into the needle track. The 29 transjugular general liver
      biopsies were performed with a 19-G spring-loaded needle, under sonographic and
      fluoroscopic guidance. The transjugular technique was used for children with
      thrombocytopenia, coagulopathy, ascites, or recent bone-marrow transplantation.
      RESULTS: All biopsies yielded sufficient tissue for diagnostic studies. Bleeding
      occurred after 3 of 21 percutaneous biopsies, despite coaxial track embolization.
      No bleeding or other major complication occurred after transjugular biopsy.
      CONCLUSION: Coaxial percutaneous biopsy with track embolization was effective,
      but was not complication-free; it should be reserved for focal lesions or for
      patients at low risk of bleeding. Transjugular liver biopsy is safe and effective
      for use in high-risk pediatric oncology patients.

PMID- 10929369
TI  - Intrahepatic portosystemic venous shunt associated with biliary atresia: case
      report.
AB  - We describe an infant with intrahepatic portosystemic venous shunt (IPSVS), which
      was detected by MR angiography. IPSVS is rare and its cause is disputed. However,
      with improvements in imaging the number of reports of IPSVS identified
      incidentally in patients without definite symptoms is increasing. The present
      case is the first associated with congenital biliary atresia and the youngest
      reported in the literature.

PMID- 10929370
TI  - Extralobar pulmonary sequestration with venous drainage to the portal vein: a
      case report.
AB  - Venous drainage to the portal vein in pulmonary sequestration is rare. A 7-month
      old girl was referred to our hospital following surgery for ventricular septal
      defect because of a left upper abdominal mass with a large feeding artery from
      the abdominal aorta and venous drainage to the portal vein. She had had frequent
      pulmonary infections and was growth retarded. MRI demonstrated that the mass was
      above the left diaphragm, suggesting extralobar sequestration. An extralobar
      sequestered lung was resected at thoracotomy. Diagnostic problems and clinical
      features are presented.

PMID- 10929371
TI  - Another perspective as to the cause of bone fractures in potential child abuse.

PMID- 10929372
TI  - Ascariasis of the gallbladder.

PMID- 10929373
TI  - Using blueberry juice as a negative contrast agent in paediatric MR urography.

PMID- 10929374
TI  - Aicardi's syndrome: a new finding.

PMID- 10929375
TI  - Bone age discrepancy on hand radiographs.

PMID- 10929376
TI  - Molecular mechanisms of radiation carcinogenesis and the linear, non-threshold
      dose response model of radiation risk estimation.
AB  - Recent research in molecular radiation carcinogenesis is reviewed with the
      specific aim of exploring the implications this research may have on the dose
      response relationship of radiation-induced cancer at low doses and low dose
      rates. It is concluded that the linear non-threshold dose response hypothesis may
      be used in radiation protection planning as a simple, convenient method to
      optimize procedures and regulations, but should not be mistaken as a stringent
      scientific conclusion directly derived from the present state of knowledge of the
      processes involved in radiation carcinogenesis.

PMID- 10929377
TI  - Analysis of thyroid cancer data from the Ukraine after 'Chernobyl' using a two
      mutation carcinogenesis model.
AB  - The thyroid cancer data of children in the northern regions of the Ukraine after
      the reactor accident at Chernobyl were combined with thyroid dose measurements in
      the same regions and analysed using a two-mutation carcinogenesis model. The best
      fit was obtained for radiation acting as an initiating agent, i.e. on the first
      mutation of the model. The observed relatively high increase of thyroid cancer
      incidence after 1990 in children exposed to radiation released after the reactor
      accident could be ascribed to the high thyroid doses and the relatively low
      background thyroid cancer incidence in children. The maximum annual incidence is
      predicted to occur fairly soon after the reactor accident, i.e. about 10 years.
      For adults, the predicted relative increase of annual thyroid cancers is much
      lower than for children younger than 20 years. The modelling results are used to
      derive risk estimates for radiation-induced thyroid cancer. These risk estimates
      are dependent on age at exposure, follow-up time and the background thyroid
      cancer incidence. The calculated excess absolute risk for a population of all
      ages is about one-third of that currently used by ICRP, but for children the
      calculated absolute risks are about a factor of 3 higher than derived in other
      epidemiological studies. The model results indicate that the excess absolute
      radiation risk per unit dose for children is about the same as or a little lower
      than that for adults.

PMID- 10929378
TI  - Current development of the human and environmental contamination in the Bryansk
      Gomel Spot after the Chernobyl accident.
AB  - Up to 1991, it was assumed that after the Chernobyl accident in 1986 the time
      development of radioactive contamination with regard to environment, foodstuff,
      and man would decrease due to migration processes in the soil, radioactive decay,
      and protective measures. This assumption was confirmed by all measurements in the
      first few years after the accident. Since 1991, however, a change in this
      development has been observed, as many measurements show stagnation or in some
      cases even an increase of foodstuff and human contamination. If normalised to an
      average local ground contamination, only a few groups of foodstuffs (e.g.,
      potatoes) show a slight decrease in radioactivity. In this paper, the time
      development of radioactive contamination in the Bryansk-Gomel Spot on the basis
      of measurements since 1991 is presented. The consequences for long-term dose
      assessment are discussed.

PMID- 10929379
TI  - A polymer, random walk model for the size-distribution of large DNA fragments
      after high linear energy transfer radiation.
AB  - DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not
      located randomly in the genome: recent data indicate DSB clustering along
      chromosomes. Stochastic DSB clustering at large scales, from > 100 Mbp down to <
      0.01 Mbp, is modeled using computer simulations and analytic equations. A random
      walk, coarse-grained polymer model for chromatin is combined with a simple track
      structure model in Monte Carlo software called DNAbreak and is applied to data on
      alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular
      details but systematically incorporates an increase in average spatial separation
      between two DNA loci as the number of base-pairs between the loci increases.
      Fragment-size distributions obtained using DNAbreak match data on large fragments
      about as well as distributions previously obtained with a less mechanistic
      approach. Dose-response relations, linear at small doses of high linear energy
      transfer (LET) radiation, are obtained. They are found to be non-linear when the
      dose becomes so large that there is a significant probability of overlapping or
      close juxtaposition, along one chromosome, for different DSB clusters from
      different tracks. The non-linearity is more evident for large fragments than for
      small. The DNAbreak results furnish an example of the RLC (randomly located
      clusters) analytic formalism, which generalizes the broken-stick fragment-size
      distribution of the random-breakage model that is often applied to low-LET data.

PMID- 10929380
TI  - Reaction rate coefficients of hydroxyl radical-induced DNA single- and alpha-type
      double-strand breaks.
AB  - With a model system of pBR322 plasmid DNA solution in vitro, the dose effects of
      radiation-induced single- and double-strand breaks (SSB and DSB) were measured
      and DSB was distinguished into alpha- and beta-types. Under the condition of low
      scavenging capacity existing in the irradiated DNA solution, SSB and alpha DSB
      were mainly induced by hydroxyl radicals (.OH). Moreover, a certain relationship
      was obtained between the SSB and alpha DSB yields and the DNA concentration. It
      was found that when the DNA solution was irradiated in the presence of 2.5 mmol
      dm-3 mannitol, the reciprocals of G(SSB) and G(alpha DSB), respectively, were
      linearly related to the reciprocal of the DNA concentration, i.e. the competition
      reactions of DNA and mannitol for .OH radicals can be described by second-order
      kinetics. The rate coefficients and the efficiencies of the .OH radical inducing
      SSB were deduced. Also, the reaction rate coefficients and the efficiencies for
      the induction of alpha DSB from SSB by the .OH radical transfer mechanism, were
      first derived from the competition kinetics.

PMID- 10929381
TI  - A novel 210Po-based alpha-particle irradiator for radiobiological experiments
      with retrospective alpha-particle hit per cell determination.
AB  - A new experimental design for alpha-particle irradiation of cells in vitro is
      described where the alpha-particle irradiator is based on a 210Po radioactive
      source. In the described set-up cells are grown directly on an alpha-particle
      detector and irradiation is done from below. For an irradiated cell dish the
      number of alpha-particle traversals through each individual cell is scored by
      using retrospective track etch dosimetry and an accurate technique for individual
      cell relocation. Calibration experiments characterizing the new irradiator system
      are presented.

PMID- 10929382
TI  - Effects of microwaves (900 MHz) on the cochlear receptor: exposure systems and
      preliminary results.
AB  - The purpose of this paper is to present the experimental device and the work in
      progress performed in search for objective organic correlation of damage to
      hearing, examining possible acoustic otofunctional effects on the cochlear
      epithelium of the rat due to exposure to microwaves (900 MHz). Two experiments
      using male Sprague-Dawley rats were carried out with a far-field exposure in a
      cubic chamber. No statistically significant evidence was obtained at both
      specific absorption rate (SAR) values. The exposure system and the diagnostic
      apparatus are extremely useful to investigate a potential effect on the auditory
      system: however, with the parameters applied in these experiments, no evidence
      was observed.

PMID- 10929383
TI  - Radon progeny activity in sweat following radon exposure in a warm and humid
      environment.
AB  - The objective was to evaluate whether activity of radon progenies can be detected
      in sweat following speleotherapeutic radon exposure (40 kBq/m3) in a warm (38
      degrees C) and humid (relative humidity > 70%) environment. A group of 11 male
      patients with spondyloarthropathy (n = 6) or non-inflammatory rheumatic diseases
      (n = 5) underwent a 1-h treatment in the gallery of the Gasteiner Heilstollen,
      and 20 min after leaving the treatment area radon progeny activity was measured
      in sweat by utilizing a special filter set. The results suggest that radon is
      discharged with sweat, causing a significant activity of radon and radon
      progenies on the skin. This finding may be important from a clinical point of
      view, since specialists experienced in radon therapy have repeatedly emphasized
      the importance of the degree of radioactivity on the skin for the effectiveness
      of treatment. It has even been claimed that the skin is the major target for
      radon therapy, possibly because of the influence on Langerhans' cell function.

PMID- 10929384
TI  - Evaluation of 133Xe for x-ray fluorescence analysis of cadmium in vivo: a Monte
      Carlo study.
AB  - A Monte Carlo model has been developed to support the design of a 180 degrees
      geometry x-ray fluorescence system for the measurement of cadmium concentration
      in deep body organs such as the kidney. 133Xe was investigated as the excitation
      photon source. A total number of 15 x 10(6) simulated incident photons were used.
      Monte Carlo simulations were performed using the EGS4 Monte Carlo code system.
      The results showed that for distances between the skin and the kidney surface of
      30-60 mm, respectively, cadmium concentrations of 15-60 micrograms/g kidney
      tissue could easily be detected. The mean skin and kidney doses during such
      measurements were estimated to be between 8 and 0.9 mGy, respectively.

PMID- 10929385
TI  - [Aspects of internal medicine].
AB  - Chronic infectious diseases may run over many months and years, accompanied by
      only mild clinical signs and often without organ-specific symptoms. People with
      any kind of immuno deficiency are more frequently affected by chronic infections.
      History, physical examination, laboratory tests, microbiological tests and
      imaging methods may lead to an exact diagnosis. The most important differential
      diagnosis are autoimmune diseases, amyloidosis and malignant lymphoma.

PMID- 10929386
TI  - [Chronic infections of the paranasal sinuses].
AB  - PURPOSE: Evaluation of the clinical value of imaging techniques for chronic
      inflammatory disease of paranasal sinuses. MATERIALS AND METHODS: Beside clinical
      tests imaging of the paranasal sinuses is based on the techniques like
      conventional X-ray studies, ultrasound, computed tomography and magnetic
      resonance techniques. RESULTS: The value of conventional X-ray is lowered and is
      today focused on the diagnosis of acute sinusitis with fluid level and the
      detection of inflammatory foci. Spiral-CT using transverse and coronal
      orientation or reformatted images is considered as the diagnostic method of
      choice for the majority of clinical questions. MRT allows additional diagnostic
      informations in completely obstructed maxillary sinuses and patients with
      suspected anterior skull base involvement. CONCLUSION: Imaging techniques do
      provide substantial diagnostic informations in patients with chronic sinusitis.

PMID- 10929387
TI  - [Pulmonary tuberculosis--the current radiological diagnosis of an old disease].
AB  - INCIDENCE: Decreasing numbers of tuberculosis cases in the western countries have
      led to diminished attention towards this disease. But worldwide, tuberculosis
      still is the leading cause of mortality due to any one single infectious agent.
      In the industrialized countries, immigration, growth of low-income groups and
      increasing numbers of immunocompromised patients, mainly due to the HIV epidemic,
      supply a reservoir for tuberculosis. DIAGNOSIS: Because of the option of a
      specific therapy, early diagnosis of tuberculosis is crucial for the course of
      the disease. In cases of multidrug resistant strains, further spread has to be
      prevented. Radiology with chest films and computed tomography has a central role
      in diagnosing tuberculosis. FINDINGS: However, as the disease produces a broad
      spectrum of radiographic findings, there are often difficulties in determining
      the underlying diagnosis. Additionally, there have been reports of atypical
      presentations of tuberculosis in immunocompromised as well as immunocompetent
      patients. This article reviews the current state of radiological diagnosis of
      pulmonary tuberculosis.

PMID- 10929388
TI  - [Fungal pneumonia].
AB  - Concomitant with advances in medicine, involving the development and use of
      antibiotics, immunosuppressive drugs, organ/stem cell transplantation and pre
      existing illnesses such as AIDS, the frequency of fungal infection has increased
      dramatically. These factors determine the susceptibility of the lung for an acute
      or chronic course of disease. Early detection, characterisation and follow-up of
      the pulmonary infiltrates is the major task of the radiologist. The correct
      timing to perform an investigation and adequate technique are an additional
      essential factor in this setting. Furthermore, radiological procedures support
      the clinicians in identifying the underlying micro-organism. The radiologist can
      suggest which micro-organism might cause the infiltrate. Certain findings and
      patterns can point to a specific causative agent, but experience, local
      epidemiology and clinical information are necessary for the differential
      diagnosis of infiltrates in long-term immunocompromised hosts. In addition,
      radiological techniques are useful in guiding interventions for identification of
      the underlying micro-organism or for therapeutical procedures. This review
      summarises useful radiological information of appearance and complications of
      fungal pneumonia.

PMID- 10929389
TI  - [Chronic infections of the biliary system].
AB  - Chronic inflammation of the gallbladder and the biliary tract due to infections
      are rare, compared to common cholelithiasis and acute biliary inflammation. This
      group of diseases includes, besides of chronic cholecystitis with cholelithiasis,
      also chronic gallbladder inflammation without stones, gallbladder hydrops and
      porcelain gallbladder. The most common form of chronic biliary tract infection is
      primary sclerosing cholangitis, while infection due to parasites like oriental
      cholangiohepatitis is very rare in Europe. Using imaging modalities like
      ultrasonography, computed tomography and magnetic resonance imaging, normally,
      besides of porcelain gallbladder, only indirect signs of the disease may be
      documented. However, when i.v. cholangiography, endoscopic-retrograde
      cholangiography, percutaneous transhepatic cholangiography or MR-cholangiography
      are performed, depiction, especially of the biliary tree, is feasible.
      Differentiation of benign stricture and malignant tumor stenosis is problematic
      unrelated to the imaging modality used. Due to the unspecific signs of the
      disease, diagnosis may not be made from imaging alone, but a clinical suspicion
      may be strengthened.

PMID- 10929390
TI  - [The imaging of chronic renal infections].
AB  - From pathological point of view the chronic renal infections include two types,
      interstitial chronic pyelonephritis and granulomatous pyelonephritis, namely
      xanthogranulomatous, malacoplakia and renal tuberculosis. Indications for imaging
      modalities are more common compared to the acute types and allow to depict both
      factors causing obstruction and infection such as stones ant the renal and
      extrarenal extension of the disease. In this article the authors review the
      findings and the role of plain film and urography, computed tomography and
      ultrasonography.

PMID- 10929391
TI  - [Chronic infections of the skeletal system. Their imaging diagnosis].
AB  - The diagnosis of chronic osteomyelitis is made on the basis of clinical,
      radiologic and histologic findings. The role of imaging in patients with known
      chronic osteomyelitis is to detect and to delineate areas of active infection. To
      correctly interpret the imaging findings, it is essential to take both the
      individual clinical findings and previous imaging studies into account. Reliable
      signs of active infection are bone marrow abscess, sequestra and sinus tract
      formation. Only the combined evaluation of bony changes together with alterations
      of the adjacent soft tissues provides good diagnostic accuracy. Projection
      radiography gives an overview of the condition of the bone, which provides the
      basis for follow-up and the selection of further imaging modalities. Computed
      tomography can be used to evaluate even discrete or complex bony alterations and
      to guide percutaneous biopsy or drainage. Magnetic resonance imaging achieves the
      best diagnostic sensitivity and specificity and provides superior contrast as
      well as anatomical resolution in both bone marrow and soft tissues. In this paper
      the features and clinical relevance of imaging in primary chronic osteomyelitis,
      posttraumatic osteomyelitis, tuberculous spondylitis and osteomyelitis of the
      diabetic foot are reviewed, with particular respect to MRI.

PMID- 10929392
TI  - [Plasma-cell osteomyelitis of the thoracic spine--a case report].
AB  - The authors report the case of a young patient suffering from plasmacellular
      osteomyelitis of the thoracic spine, a unusual localisation of this type of
      chronic osteomyelitis. They discuss the role of imaging diagnostic modalities in
      this disease, focussing on MRI.

PMID- 10929393
TI  - [The diagnostic potentials of nuclear medicine in chronic infections].
AB  - BACKGROUND: The availability of high-sensitive radiopharmaceuticals for the
      diagnosis of an unknown focus of infection with whole body scanning and SPECT and
      the availability of high specific radiopharmaceuticals for the detection of a
      leucocytic infiltration are the basis of the high potential of nuclear medicine
      in patients with chronic infections. Both procedures are always complementary to
      radiological procedures, which can specify and better determine a detected focus
      and which can induce also infection imaging if the radiologic result is
      ambiguous. RADIOPHARMACEUTICALS: Not all available radiopharmaceuticals for the
      nuclear medicine imaging of infection and inflammation, i.e. 99mTc-nanocolloids,
      99mTc-labelled human immunoglobulin, 99mTc-HMPAO and 111In-oxin labelled
      leukocytes, 67Ga-citrate, 99mTc-labelled antigranulocyte antibodies and their
      fragments and 18F-FGD-PET, are useful in all clinical situations, because there
      are differences in the availability, the radiation exposure, the costs and the
      underlying patho-physiological mechanism.

PMID- 10929394
TI  - [The radiological and surgical management of nonpalpable breast lesions].
AB  - In this retrospective study the results of surgical biopsy of suspected breast
      cancer in 319 outpatients are reported. In 113 cases (35.4%) the lesion was
      palpable, in 206 cases (64.6%) it was not. Concerning the nonpalpable lesions,
      mammography was performed in 98 patients (47.6%) for work-up of fibrocystic
      changes, in 41 patients (19.9%) for initial participation in a breast cancer
      prevention program, and in 33 patients (16.0%) for surveillance after breast
      conservation therapy. Prior to operation, 84.0% (n = 173) of the nonpalpable
      lesions were detected by mammography, 11.2% (n = 23) by sonography, and 4.8% (n =
      10) by magnetic resonance imaging. Intra-operative specimen mammography was
      carried out in every case detected by mammography. In 19.4% (n = 40) of 206
      nonpalpable lesions a malignant tumor was found. Twenty-five percent (n = 10) of
      all marked tumors were diagnosed and treated as in-situ stage tumors, while 65%
      (n = 26) were diagnosed and treated as tumors in the pT1 stage. As regards the
      nodal stage, 85% (n = 34) of the tumors were diagnosed and treated as pNO tumors,
      and 100% (n = 40) were found to be free from any distant metastases.
      Consequently, for improving prognosis and, at the same time, for reducing the
      rate of breast amputations as a means of curative therapy of breast cancer,
      regular screening in defined risk groups is necessary. Surgical treatment of
      patients with small and nonpalpable findings should be reserved for departments
      with marking and quick-freezing facilities.

PMID- 10929395
TI  - [Cancer research requires staying power].

PMID- 10929396
TI  - [Atypical prosthetic loosening in the hip joint].

PMID- 10929397
TI  - [Kidney diseases in childhood. 1. Imaging procedures, diseases of the kidneys and
      the excretory urinary tract].

PMID- 10929398
TI  - Vertebrate eye development and refractive function: an overview.

PMID- 10929399
TI  - Pax6 and the genetic control of early eye development.

PMID- 10929400
TI  - Early retinal development in Drosophila.

PMID- 10929401
TI  - Induction of the lens.

PMID- 10929402
TI  - Molecular control of cell diversification in the vertebrate retina.

PMID- 10929403
TI  - Cell fate specification in the Drosophila retina.

PMID- 10929404
TI  - Roles of the extracellular matrix in retinal development and maintenance.

PMID- 10929405
TI  - Adhesive events in retinal development and function: the role of integrin
      receptors.
AB  - Cells in the developing retina contact a vast array of molecular cues in their
      microenvironment that are thought to guide their development. Many of these cues
      are embedded in the surface of neighboring cells or deposited within the
      extracellular matrix (ECM). Evidence has accumulated that cell-cell and cell-ECM
      interactions are essential in many phases of neural development, including
      neuroblast migration, determination of cell fate, axon outgrowth and synapse
      formation. In this chapter, we examine the developmental and functional roles
      fulfilled by integrins, a family of receptors for ECM molecules and cell adhesion
      molecules (CAMs). We have approached this problem by addressing a series of three
      questions: (1) which integrins are expressed in developing retina? (2) when and
      where are they expressed? and, (3) what functions do they carry out? Integrins
      have previously been implicated in axon extension, but new evidence suggests that
      they are also involved in earlier developmental events in preaxonal neuroblasts.
      High levels of expression of at least eight integrin subunits have been
      documented in these young retinal cells, and integrins containing the beta 1
      subunit have been implicated in migration of adolescent retinal ganglion cells.
      Integrin expression persists through adulthood, both in the retina and in the
      neighboring layer of the retinal pigment epithelium (RPE). The integrin alpha v
      beta 5 has been shown to reside on the apical surface of the RPE and has been
      implicated in the phagocytosis of shed photoreceptor outer segments.

PMID- 10929406
TI  - Connecting the eye with the brain: the formation of the retinotectal pathway.

PMID- 10929407
TI  - Regeneration of the lens in amphibians.

PMID- 10929408
TI  - How the neural retina regenerates.

PMID- 10929409
TI  - Mouse mutants for eye development.

PMID- 10929410
TI  - Genetic analysis of eye development in zebrafish.

PMID- 10929411
TI  - Pectoralis major muscle and tendon tears: diagnosis and grading using magnetic
      resonance imaging.
AB  - OBJECTIVE: To assess the accuracy and utility of magnetic resonance (MR) imaging
      in the detection and grading of pectoralis major muscle and tendon tears. DESIGN
      AND PATIENTS: A retrospective review was carried out of 10 patients referred for
      MR imaging for suspected pectoralis muscle injury and possible operative therapy.
      The pectoralis muscle and tendon were imaged using thin (3-4 mm) axial sections
      with a variety of sequences combined for anatomical delineation (T1-weighted SE
      or PD SE) and fluid detection (T2-weighted SE, T2-weighted FSE with fat
      suppression, or STIR). Surgical correlation was available in six patients.
      Clinical follow-up was available in four patients treated by nonoperative
      therapy. RESULTS: MR imaging identified five complete tears, four partial tears
      and one normal tendon. One complete and one partial tear were at the myotendinous
      junction. The remaining seven injuries were at the enthesis. Surgical correlation
      consisted of five complete tears and one partial tear. One complete and one
      partial tear were at the myotendinous junction with the remaining four complete
      tears at the enthesis. The MR interpretation and surgical findings were in
      agreement in all six cases. All four patients treated with nonoperative therapy
      demonstrated improvement at a clinical follow-up examination, with restoration of
      function and strength consistent with a healed prior partial injury. CONCLUSION:
      MR imaging is accurate and useful in detecting and grading tears involving the
      pectoralis major muscle and tendon, facilitating the identification of patients
      with complete tears who are candidates for operative therapy.

PMID- 10929412
TI  - MR imaging after rotator cuff repair: full-thickness defects and bursitis-like
      subacromial abnormalities in asymptomatic subjects.
AB  - OBJECTIVE: To determine the prevalence and extent of residual defects or retears
      and bursitis-like subacromial abnormalities on MR images after rotator cuff
      repair in asymptomatic subjects, and to define the clinical relevance of these
      findings. DESIGN AND PATIENTS: Fourteen completely asymptomatic patients and 32
      patients with residual symptoms were investigated 27-53 months (mean 39 months)
      after open transosseous reinsertion of the rotator cuff. Coronal T2-weighted
      turbo spin-echo and turbo STIR or T2-weighted fat-suppressed MR images were
      obtained. The prevalence and extent of residual defects or retears of the rotator
      cuff and bursitis-like subacromial abnormalities were determined. RESULTS:
      Residual defects or retears were detected in three (21%) and bursitis-like
      abnormalities in 14 (100%) of the 14 asymptomatic patients. Fifteen (47%)
      residual defects or retears and 31 (97%) bursitis-like abnormalities were
      diagnosed in the 32 patients with residual symptoms. The size of the residual
      defects/retears was significantly smaller in the asymptomatic group (mean 8 mm,
      range 6-11 mm) than in the symptomatic group (mean 32 mm, range 7-50 mm) (t-test,
      P = 0.001). The extent of the bursitis-like subacromial abnormalities did not
      significantly differ (t-test, P > 0.05) between asymptomatic (mean 28 x 3 mm) and
      symptomatic patients (mean 32 x 3 mm). CONCLUSION: Small residual defects or
      retears (< 1 cm) of the rotator cuff are not necessarily associated with clinical
      symptoms. Subacromial bursitis-like MR abnormalities are almost always seen after
      rotator cuff repair even in patients without residual complaints. They may
      persist for several years after rotator cuff repair and appear to be clinically
      irrelevant.

PMID- 10929413
TI  - In vitro and in vivo spin echo diffusion imaging characteristics of synovial
      fluid: potential non-invasive differentiation of inflammatory and degenerative
      arthritis.
AB  - OBJECTIVE: This study was undertaken to analyse the diffusion characteristics of
      synovial fluid in degenerative and inflammatory arthropathies. DESIGN AND
      PATIENTS: Ten in vitro specimens of synovial fluid from patients with both
      degenerative and inflammatory arthropathy were studied at body temperature with a
      navigator-corrected spin echo diffusion sequence (B values 0-512 s/mm2), on a
      Philips 1.5-T Gyroscan. Subsequently synovial fluid from knee joint effusions of
      25 patients (10 patients with osteoarthritis, 10 patients with effusions
      following trauma and 5 patients with effusions secondary to inflammatory
      arthritis) was evaluated with the same navigator-corrected spin echo diffusion
      sequence. RESULTS: Both in vitro and in vivo study demonstrated decreased
      diffusion in patients with effusions secondary to degenerative joint disease
      (less than 2.40 x 10(-5) cm2/s) relative to patients with effusions accompanying
      knee trauma (greater than 2.75 x 10(-5) cm2/s) and inflammatory arthritis (in
      vitro and in vivo greater than 3.00 x 10(-5) cm2/s). CONCLUSION: Synovial fluid
      in degenerative arthritis shows less diffusion or free water movement than
      synovial fluid in inflammatory arthritis. Diffusion characteristics of synovial
      fluid may be used to predict the nature of the underlying form of arthritis in
      patients presenting with knee joint effusions.

PMID- 10929414
TI  - Magnetic resonance imaging of rheumatoid arthritis in metacarpophalangeal joints.
AB  - OBJECTIVE: To report the development of high-resolution targeted magnetic
      resonance imaging (MRI) techniques (not using injections of contrast media) to
      investigate and monitor rheumatoid arthritis (RA) in the metacarpophalangeal
      (MCP) joints. DESIGN AND PATIENTS: A total of 25 RA patients (age range 30-68
      years) with varying degrees of disease severity ranging from early onset through
      active disease to the burnt-out stage, were imaged. (One patient subsequently
      underwent surgery and histological data was obtained.) A series of 10 control
      subjects were also studied--two for each 10-year age range. All the RA subjects
      were assessed for disease activity using standard clinical criteria and
      radiography as part of normal procedures. MRI was carried out using a targeted
      system and novel radiofrequency coil. Images of the MCP were performed at very
      high resolution with 1.5 mm slice thickness and in-plane resolution 130 microns.
      Standard gradient-echo (GE) sequences were used for anatomical imaging, multiple
      echo GE sequences used to produce effective spin-spin relaxation time (T2*) maps
      and optimised binomialpulse presaturation used in conjunction with a GE sequence
      to generate magnetization-transfer (MT) ratio maps. RESULTS: High-quality high
      resolution images of the MCP joints were obtained which highlighted normal
      anatomy and key features characterising the disease state (e.g. pannus, bone
      erosions, vascularity). Accurate measurements of T2* and MT with variations of +/
      4% and +/- 2% respectively were achieved. In active disease, variations in T2*
      and MT could be determined throughout areas of pannus, clearly demonstrating the
      heterogeneity of this erosive tissue. Pannus in MCP joints with active
      destruction was found to have high values of T2* varying from 25 ms to 40 ms with
      pockets up to 100 ms, whereas pannus present in chronic destruction, or burnt-out
      disease, had T2* values ranging from 21 to 29 ms. MT-active tissue was uniformly
      distributed in burnt-out disease, which was confirmed histologically in one case,
      compared with a more heterogeneous distribution in active disease. CONCLUSION:
      The MRI sequences and targeted system developed allow high-resolution studies of
      RA disease progression and activity. The data confirm the variable pattern of the
      disease and, in particular, heterogeneity of pannus.

PMID- 10929415
TI  - Pasteurized intercalary autogenous bone graft: radiographic and scintigraphic
      features.
AB  - OBJECTIVE: Pasteurized autogenous bone graft sterilized at a low temperature (60
      degrees C) is one option for reconstruction after resection of bone and soft
      tissue tumors. The purpose of this investigation was to assess the normal and
      abnormal radiographic and scintigraphic findings of pasteurized intercalary
      autogenous bone graft after resection of bone and soft tissue sarcomas. DESIGN:
      This was a retrospective evaluation of the radiography and bone scintigraphy
      findings in patients after treatment of bone and soft tissue sarcomas using an
      intercalary pasteurized autogenous bone graft. PATIENTS: Among 10 consecutive
      patients, eight had intercalary grafts, and they constitute the subjects of this
      study. All available radiography and bone scintigraphy findings were reviewed for
      the healing process and the possibility of complications. RESULTS AND
      CONCLUSIONS: Healing and incorporation of the graft were observed in five
      patients during the follow-up, but the other three did not heal satisfactorily.
      Rapid incorporation of pasteurized autogenous bone graft can be demonstrated by
      means of radiography and bone scintigraphy.

PMID- 10929416
TI  - Prevertebral soft tissue swelling following trauma: usefulness following tube
      placement.
AB  - OBJECTIVE: Prevertebral soft tissue swelling (PVSTS) is an important marker of
      spinal trauma. In patients with missed or occult cervical fractures, it may be
      the only indication of serious injury. It has been anecdotally suggested that
      PVSTS is not useful following placement of a nasogastric (NGT) or endotracheal
      (ETT) tube because of possible iatrogenic trauma and/or soft tissue compression.
      Consequently, we investigated trauma patients for evidence of PVSTS, comparing
      radiographs performed before and after placement of NGTs and/or ETTs. DESIGN AND
      PATIENTS: PVSTS at the C2 and C6 levels was measured on lateral cervical spine
      radiographs in 102 patients with cervical spine fractures. Measurements were
      obtained in 66 patients before and after placement of either an NGT (23), ETT
      (8), or both an NGT and ETT (35). They were also obtained in 36 control patients
      with fractures and neither an NGT nor ETT, at presentation and after an interval
      temporally matched to that in the patients with tubes in place. RESULTS: The
      group with ETTs showed variable changes to PVSTS (31% increase, 63% decrease, and
      6% no change). The group with NGTs also showed variable changes to PVSTS (33%
      increase, 53% decrease, and 13% no change). The group with ETTs and NGTs
      similarly showed variable changes to PVSTS (25% increase, 72% decrease, 3% no
      change). Surprisingly, the control group showed similar temporal changes without
      tube placement (49% increase, 36% decrease, 13% no change). Analyses using the
      one-tailed F-test of the ratio of the variance of the tube to non-tube groups and
      the Mann-Whitney test were performed. No significant difference was found in the
      prevertebral soft tissues at the C2 level between those with tubes in place and
      the control subjects. However, at the C6 level there was statistical significance
      between the groups with NGTs and both NGTs and ETTs versus the non-tube groups.
      Probability under the F-test for the groups with NGTs and both NGTs and ETTs was
      0.001 and 0.005, respectively. Under the Mann-Whitney test, P values for groups
      with NGTs and both NGTs and ETTs were 0.0002 and 0.0001, respectively.
      CONCLUSION: The appearance of PVSTS showed variable and unpredictable changes
      following ETT, NGT, or combined ETT/NGT placement at the C2 level. This appears
      to be an artifact of temporal changes. However, at the C6 level, the presence of
      PVSTS following NGT or ETT and NGT placement (but not ETT placement alone) may be
      an accurate indirect sign of cervical spine injury.

PMID- 10929417
TI  - Bilateral metachronous periosteal tibial amyloid tumors.
AB  - Localized primary periosteal amyloid tumors are extremely rare. A case of
      bilateral tibial amyloid tumor is presented. A 62-year-old woman initially
      presented with a painful mass in the anterior aspect of the right leg. There was
      no evidence of underlying systemic disease, including chronic infection or
      malignancy. Based on the results of resistance with Congo red staining to
      treatment with potassium permanganate and positivity for kappa light chain, we
      classified this particular case as AL-type amyloidosis. The patient noticed a
      swelling in the opposite leg 2 years later. The second tumor was also an AL-type
      amyloidoma. Amyloid tumors are generally solitary. This is the first case of
      bilateral periosteal amyloid tumors of the AL-type occurring in the tibiae.

PMID- 10929418
TI  - Multifocal osteogenic sarcoma in Paget's disease.
AB  - The most serious complication of Paget's disease is sarcomatous degeneration of
      pagetic bone. Multifocal sarcomatous degeneration occurs mainly in polyostotic
      Paget's disease. Multifocal Paget's sarcoma is uncommon and can arise in any
      site. We report two cases of synchronous multifocal sarcomatous degeneration. The
      two patients were elderly women (aged 77 and 86 years, respectively) who
      developed sarcomatous lesions concomitantly, in the first case report in left
      ilium, left tibia, and first lumbar vertebra and in the second case report in the
      skull, right ilium, and sacrum. Whether these cases are due to the simultaneous
      development of several primaries or to metastases from a single primary remains
      unclear.

PMID- 10929419
TI  - Intraosseous microcystic meningioma.
AB  - Extradural ectopic meningioma is a rare tumor. We report on an example of
      microcystic meningioma arising in the skull of an elderly woman. Radiological
      examination revealed a localized osteolytic lesion in the left parietal bone. At
      surgery, it was discovered that the tumor was located within the skull without
      any evidence of extraosseous extension. The light microscopic,
      immunohistochemical and ultrastructural features were consistent with a
      microcystic variant of meningioma. To our knowledge, this is the first case of an
      intraosseous microcystic meningioma, and we believe that this type of meningioma
      should be considered in the differential diagnoses of myxoid bone tumors of the
      calvarium.

PMID- 10929420
TI  - Mannosidosis: an unusual cause of a deforming arthropathy.
AB  - We report on a case of a deforming arthropathy in a young man with a lysosomal
      storage disorder. A 31-year-old man with a known diagnosis of mannosidosis
      presented with a painful swollen right elbow. Radiographs of his right elbow
      showed a disorganised joint with multiple fragments resembling the appearances of
      a neuropathic joint. This case provides further evidence that a deforming
      arthropathy may occur as part of the spectrum of skeletal abnormalities seen in
      mannosidosis.

PMID- 10929421
TI  - Complete rupture of the distal semimembranosus tendon with secondary hamstring
      muscles atrophy: MR findings in two cases.
AB  - Complete rupture of the hamstring muscles is a rare injury. The proximal musculo
      tendinous junction is the most frequent site of rupture. We present two cases of
      complete rupture of the distal semimembranosus tendon, which clinically presented
      as soft-tissue masses. MR imaging permitted the correct diagnosis. There has been
      only one other such case reported.

PMID- 10929422
TI  - Nucleation and aggregation of calcium oxalate in whole urine; spectrophotometric
      sedimentation analysis: a new approach to study the aggregation of calcium
      oxalate dihydrate.
AB  - Spectrophotometric and scanning electron microscopic (SEM) studies of oxalate
      induced crystallization have been performed in whole urine with and without
      continuous magnetic stirring and before and after millipore filtration of urine.
      With continuous stirring, preferential nucleation was observed and this followed
      second order kinetics. Important crystal aggregation only occurred after an
      oxalate load above 1 mmol/l and without stirring. Under these conditions and at
      an ionic calcium concentration of 2 mmol/l, single crystals and aggregates of
      calcium oxalate dihydrate and monohydrate of well defined sizes were produced.
      Single dehydrates, their aggregates and the other particles could be
      distinguished by their significantly different sedimentation rates. From
      sedimentation curves an aggregation ratio for calcium oxalate dihydrate
      (aggregated/total dihydrate particles) was extrapolated. Millipore filtration
      removing important urinary macromolecules increased this aggregation ratio as
      well as the size of the aggregates on SEM pictures.

PMID- 10929423
TI  - Loss of regulation of circulating 1,25-dihydroxyvitamin D with paradoxically
      decreased serum phosphate levels in individuals with recurrent kidney stones.
AB  - A low serum phosphate concentration is characteristic in individuals in whom
      kidney stones form, this being related to serum 1,25-dihydroxyvitamin D,
      parathyroid hormone and urinary phosphate excretion. In order to determine
      whether these parameters are related to recurrence of stone formation, they were
      analyzed in single and recurrent stone formers as well as controls. An inverse
      correlation between serum levels of phosphate and 1,25-dihydroxyvitamin D was
      observed in control subjects, indicating that a drop in serum phosphate results
      in upregulated circulating 1,25-dihydroxyvitamin D level in controls. While the
      circulating low phosphate level upregulated the 1,25-dihydroxyvitamin D level in
      single stone formers, the elevation was less than expected from the drop in serum
      phosphate in recurrent stone formers. The results thus suggest that loss of
      upregulation of 1,25-dihydroxyvitamin D by serum levels of phosphate might be
      important for stone formation. The possibility of deregulation of 1,25
      dihydroxyvitamin D to maintain physiological requirements in stone formers and
      prevent further nephrolithiasis therefore warrants attention.

PMID- 10929424
TI  - Analysis of osteopontin DNA in patients with urolithiasis.
AB  - We previously reported the importance of osteopontin (OPN) in the formation of
      urinary calculus. Since OPN protein is present in normal kidneys, we investigated
      the difference in OPN at the DNA level between normal subjects and urolithiasis
      patients. There has not been any genetic investigation of OPN in familial
      urolithiasis previously reported worldwide. To confirm hereditary predisposing
      factors for urolithiasis, changes in OPN DNA within a family were investigated in
      relation to the presence or absence of urinary calculus. Leukocyte OPN DNA from
      two normal subjects and five patients with urinary calculus was investigated by
      SSCP analysis: OPN DNA nucleotide sequence was determined, based on the result of
      SSCP analysis. As a result, a mutation of GCC to GCT, encoding amino acid
      position 250 (Ala-250) was found. To confirm the frequency of mutation at this
      site, OPN DNA was extracted from peripheral blood in 36 normal subjects (Con
      group), 25 patients with familial urolithiasis (FSF), and 40 patients with
      recurrent urinary calculus and who had had two or more previous episodes (RSF).
      The degree of mutation at Ala-250 was then examined by restriction fragment
      length polymorphism (RFLP) method. As described above, the nucleotide codon
      encoding the amino acid sequence position 250, Ala-250, was GCC in two normal
      subjects. This is the original codon. In five patients with urolithiasis it was
      GCT, showing a substitution of C with T. On examining the frequency of this
      mutation, the ratio of normal homozygous GCC was 11/36 in the Con group, 1/25 in
      FSF and 1/40 in RSF. The ratio of heterozygous GCC/GCT was 16/36 in the Con
      group, 15/25 in FSF and 26/40 in RSF, and the ratio of homozygous GCT was 9/36 in
      the Con group, 9/25 in FSF and 13/40 in RSF. Furthermore, the gene frequency of
      the normal codon GCC was 0.528 in the Con group, 0.3 in FSF and 0.35 in RSF,
      showing a significantly higher incidence in the Con group (P < 0.05). The gene
      frequency of mutated GCT was 0.472 in Con group, 0.7 in FSF and 0.65 in RSF,
      showing a significantly higher incidence in urolithiasis patients (P < 0.05). On
      investigating the inheritance of Ala-250 in five families in which both parent
      and offspring demonstrated urolithiasis, the nucleotide substitution in Ala-250
      in parents with urolithiasis was inherited by their offspring. In all five
      families the offspring developed urinary calculus. This study showed that there
      is no difference in OPN structure between the Con group and urolithiasis
      patients. However, it was predicted that due to the frequency of normally coded
      GCC being high in the Con group a difference in the amount of OPN might be caused
      by a difference in transcription velocity between the two groups. Furthermore, it
      was suggested that examining the inheritance of Ala-250 within a family is a
      diagnostic method for identifying the predisposing hereditary factors for
      urolithiasis patients.

PMID- 10929425
TI  - Ascorbic acid in idiopathic recurrent calcium urolithiasis in humans--does it
      have an abettor role in oxalate, and calcium oxalate crystallization?
AB  - The role of ascorbic acid (ASC) in the pathophysiology of renal calcium stones is
      not clear. We evaluated ASC in blood and urine of fasting male patients with
      idiopathic calcium urolithiasis (ICU) and healthy volunteers. Using smaller
      subgroups, we also evaluated their response to exogenous ASC [either intravenous
      or oral ASC (5 mg/kg bodyweight)] administered together with an oxalate-free test
      meal. The influence of ASC on calcium oxalate crystallization, the morphology of
      crystals at urinary pH 5, 6 and 7, and the effect of increasing duration of urine
      incubation on urinary oxalate at these pHs, without and with addition of ASC,
      were studied too. In normo- and hypercalciuric ICU, blood and urinary ASC from
      fasting patients remained unchanged, but the slope of the regression line of
      urinary ASC versus urinary oxalate was steeper than in the controls; the plasma
      ASC half-life did not differ between controls, normo- and hypercalciuric ICU; the
      ASC-supplemented meal caused an increase in the integrated plasma oxalate in the
      normocalciuric subgroup versus controls. In normo- and hypercalciuric ICU urinary
      oxalate, the oxalate/glycolate ratio, and calcium oxalate supersaturation were
      increased, but urinary glycolate was unchanged. In the controls, oral ASC did not
      affect calcium oxalate crystallization, while in ICU, ASC inhibited crystal
      growth. In control urine calcium oxalate dihydrate and calcium oxalate
      monohydrate develops, while in ICU urine only the former crystal type develops.
      In vitro oxalate neoformation from ASC did not occur. It was concluded that (1)
      under normal conditions an abettor role of ASC for renal stones is not
      recognizable, (2) in ICU, urinary oxalate excess unrelated to degradation of
      exogenous ASC is exhibited, and that this is most likely unrelated to an initial
      increase in oxalate biosynthesis, and (3) ASC appears to modulate directly
      calcium oxalate crystallization in ICU, although the true mode of action is still
      not known.

PMID- 10929426
TI  - Expression of the SART1 tumor rejection antigen in renal cell carcinoma.
AB  - We have previously described the SART1 gene, which encodes both the SART1(259)
      antigen expressed in the cytosol of the majority of squamous cell carcinomas and
      some adenocarcinomas and the SART1(800) antigen expressed in the nucleus of the
      majority of proliferating cells. The SART1(259) antigen is recognized by HLA-A24
      and A26-restricted cytotoxic T lymphocytes (CTLs). The present study investigated
      the expression of these two antigens in renal cell carcinomas (RCCs) in order to
      identify an appropriate molecule for use in specific immunotherapy for RCC
      patients. These two antigens were detected in all RCC cell lines and cells of the
      primary cultures of the RCCs tested. Further, they were detectable in cells of
      the primary cultures of non-tumorous kidney tissues. In contrast to these
      cultured cells, SART1(259) was detectable in only a few uncultured RCC tissues
      (5/20, 25%) and was undetectable in non-tumorous kidney tissues. SART1(800) was
      also scarcely detectable in uncultured RCC tissues (3/20, 15%) and non-tumorous
      kidney tissues (4/20, 20%). HLA-A2402-restricted and tumor-specific CTL (KE4-CTL)
      used for the cloning of the SART1 gene showed significant levels of cytotoxicity
      to both the cells from the RCC cell line and the cells from the primary cultures
      of RCC tissues, but did not lyse any normal cells, including cells from the
      primary cultures of non-tumorous kidney tissues. The SART1-derived peptide at
      positions 690-698 induced HLA-A24 restricted CTLs cytotoxic to RCC cells from
      peripheral blood mononuclear cells (PBMCs) of RCC patients. Therefore, the SART1
      peptide could be an appropriate molecule for use in peptide-based specific
      immunotherapy for RCC patients.

PMID- 10929427
TI  - Aberration of chromosomes 8 and 11 in bladder cancer as detected by fluorescence
      in situ hybridization.
AB  - Although a bladder cancer-specific abnormality in chromosomes or genes has not
      been reported, chromosomal regions that tend to become abnormal have been
      recognized. In this study, we investigated abnormalities in chromosomes 8 and 11.
      There were 27 patients with bladder cancer, 16 males and 11 females, who
      participated in this study. Abnormalities in chromosomes 8 and 11 were
      investigated by the fluorescence in situ hybridization (FISH) method. Probes used
      in this study were chromosome 8 alpha-satellite and chromosome 11 alpha-satellite
      (Oncor Co.). Of 27 cases, 15 cases were positive for chromosome 8 (55.6%) and ten
      cases were positive for chromosome 11 (37.0%). Since the FISH method detects
      chromosomal abnormality by the number of signals generated in cancer cells, this
      method is objective and simple and thus may be applicable in clinical practice.

PMID- 10929430
TI  - A scientific basis for the therapeutic effects of Pygeum africanum and Serenoa
      repens.
AB  - In Europe, phytotherapeutic preparations have been prescribed for the treatment
      of symptomatic benign prostatic hyperplasia (BPH) for over 20 years [1-4]. In
      these countries, phytotherapeutic preparations represent approximately 1/3 of
      total sales of all therapeutic agents sold for the treatment of BPH. In France,
      and other countries, phytotherapeutic preparations are the most widely used drugs
      for the treatment of BPH. In Asia, Africa, and India, phytotherapy is considered
      a first-line treatment for BPH and has been utilized effectively for centuries.
      In the United States, the multimillion dollar sales of phytotherapeutic
      preparations for "the health of the prostate and bladder" attests to the
      widespread utilization of these agents [3, 4]. Two of the most popular
      phytotherapeutic agents that have undergone both clinical studies to determine
      their efficacy, and have been the subject of basic science studies to identify
      the mechanism(s) of action are Pygeum africanum (Tadenan), an extract from the
      bark of the African plum tree, and Serenoa repens (Permixon), a lipido-sterol
      extract of dwarf palm. Tadenan and Permixon are registered therapeutic agents of
      Debat Pharmaceuticals, and Pierre Fabre Medicament, respectively. Manufacture of
      both preparations are tightly controlled and subjected to strict quality control
      for stability of component composition. In regard to phytotherapeutic agents,
      each individual preparation (even from the same plant source) must be considered
      individually because of differences in the extraction techniques, preparation of
      products, composition, and biological activities. Thus, the clinical and
      biological activities of one preparation cannot be extrapolated to other
      preparations of the same plant source. Thus, studies described in this review
      which utilize the preparations that are manufactured by DEBAT (Pygeum africanum)
      or Pierre Fabre Medicament (Serenoa repens) are referred to by their trade names,
      Tadenan and Permixon, to differentiate them from other nonstandardized
      preparations of the same plants.

PMID- 10929429
TI  - Expression of m2 muscarinic acetylcholine receptor mRNA in primary culture of
      human prostate stromal cells.
AB  - The aim of this study was to investigate the expression of the muscarinic
      acetylcholine receptor (mAchR) subtypes mRNA in primary culture of human prostate
      stromal cells using the reverse transcription polymerase chain reaction (RT-PCR),
      RNA blotting and in situ hybridization (ISH). Using an explant method, we
      obtained a primary culture of prostate stromal cells from three patients with
      benign prostatic hypertrophy. Total RNA was extracted using the acid guanidinium
      method for cDNA synthesis. First-strand cDNA was then used for PCR with primers
      designed to amplify the fragments of each mAchR subtypes (m1-m5) cDNA sequence.
      The m2, m3 and m4 subtype expected bands were detected; in particular m2
      transcripts was strongly detected in the stromal cell culture. Each of the PCR
      products were subcloned into the pGEM-T plasmid vector, sequenced and random
      primer labeled using 32P. Digoxigenin-labeled cRNA probes were synthesized by in
      vitro transcription. RNA blotting using a m2 muscarinic receptor cDNA probe
      revealed a 4.5 kb single transcript. However, m3 and m4 probes did not hybridize.
      Using in situ hybridization (ISH), m2 receptor mRNA signals were detected in
      several smooth muscle cells. The staining was predominantly localized to the
      perinuclear cytoplasm. The m3 and m4 probes did not hybridize. These results
      suggested that m2 receptor subtype plays a role in smooth muscle activity of the
      human prostate.

PMID- 10929428
TI  - Effect of retinoic acid and its complexes with transition metals on human bladder
      cancer cell line EJ in vitro.
AB  - The aim of this study was to investigate the effect of retinoic acid (RA) and its
      complexes with transition metals on the bladder cancer cell line EJ. Retinoic
      acid complexes with transition metals Cu, Co, Zn, and Ni were prepared. Cell
      proliferation was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT) assay in the presence of RA or its complexes with transition metals
      Cu, Co, Zn, and Ni ?Cu(RA)2.3H2O, Co(RA)2.3H2O, Zn(RA)2.4H2O, and Ni(RA)2.3H2O?.
      Colony formation in soft agar culture, A agglutination reaction, and lactic acid
      dehydrogenase isoenzyme assay were performed in the cells treated with these
      drugs to estimate the induced differentiation. p53 or c-Ha-ras expression in drug
      treated cells was assayed by ABC immunocytochemistry technique. The results
      demonstrate that EJ cells treated with the drugs become less confluent and tend
      to exhibit normal characteristics. Although RA and its complexes showed
      inhibition to proliferation of EJ cells at the concentrations of 10(-6) mmol/l,
      the inhibition induced by Ni(RA)2.3H2O was much more marked than that by RA. EJ
      cells were growth inhibited by RA or Ni(RA)2.3H2O from 48 to 96 h at the
      concentration of 10(-8) mol/l. The levels of LDH4 and LDH5 in the cells were
      greatly increased by RA. Nevertheless, Ni(RA)2.3H2O did not affect LDH isoenzyme
      in EJ cells. The number of colony formations of EJ cells in soft agar culture was
      decreased by RA or Ni(RA)2.3H2O. The percentage of colony formation in soft agar
      culture was much lower in EJ cells treated with Ni(RA)2.3H2O than with RA. The
      required concentration of A agglutination reaction was more increased for EJ
      cells treated with RA or Ni(RA)2.3H2O than for the control and was further
      increased in cells treated with Ni(RA)2.3H2O. Mutant p53 expression was more
      decreased in the EJ cells treated with RA or Ni(RA)2.3H2O than in the control.
      Although RA at the concentration of 10(-6) mmol/l caused lower p21 expression,
      Ni(RA)2.3H2O did not affect p21 expression in EJ cells. Therefore, RA and its
      transition metal complexes have a potential use in the treatment of bladder
      cancer.

PMID- 10929431
TI  - [Inhalative strategies for improvement of pulmonary hemodynamics and gas exchange
      in sepsis and severe pulmonary hypertension].
AB  - Chronic pulmonary hypertension and septic lung failure display different clinical
      features resulting in severe disturbances in the pulmonary circulation. In these
      diseases, the pulmonary bloodflow is impaired by a pathologic constriction of
      blood vessels that may lead to right ventricular overloading as well as serious
      worsening of gas exchange mainly caused by ventilation/perfusion mismatch.
      Various mechanisms deteriorating the vascular function may induce both an
      irreversible and a reversible contraction of pulmonary vessels, respectively. Two
      pharmacological approaches exist to reduce the vascular resistance: Reduction of
      the increased vascular tone by relaxation of vascular smooth muscle cells (effect
      of vasodilators). Inhibition of thrombus-mediated obliteration of the lung
      perfusion by use of anticoagulant and fibrinolytic drugs. Prevention of the
      structural reorganization of pulmonary vessels (vascular remodeling) by use of
      vasodilators with anti-inflammatory and anti-proliferative potency such as
      prostanoids. The systemic (intravenous or oral) application of vasodilative
      agents in sepsis and chronic pulmonary hypertension has, however, important side
      effects: Antagonism of the hypoxic pulmonary vasoconstriction aggravates the
      ventilation/perfusion mismatch (decrease in arterial oxygenation). Side effects
      of these vasodilators (systemic hypotension). The inhalative route of application
      is superior because of the pulmonary enrichment of the applied agent (pulmonary
      selectivity). Furthermore, a preferential deposition in the well-ventilated areas
      of the lung is achieved (intrapulmonary selectivity). Thus, the decrease in
      pulmonary-vascular resistance is paralleled by both optimized ventilation
      perfusion matching and subsequently improved gas exchange. First clinical studies
      with inhaled nitric oxide and aerosolized prostacyclin have been performed in
      intubated and mechanically ventilated patients with septic lung failure. At
      present, the use of the long-acting prostacyclin analogue ilomedin for ambulant
      treatment of patients with chronic pulmonary hypertension is under investigation.

PMID- 10929432
TI  - Risk factors for early reocclusion and luminal renarrowing in patients with acute
      coronary syndromes treated by direct PTCA with provisional stenting.
AB  - Angioplasty in acute coronary syndromes is complicated by a high rate of early
      vessel reocclusion and restenosis. Therefore, it is recommended to achieve a
      "stent-like" result by percutaneous transluminal coronary angioplasty (PTCA) or
      otherwise use coronary stenting (provisional stenting). This study sought to
      determine angiographic and patient-related factors that are associated with early
      target vessel reocclusion or luminal renarrowing after coronary intervention in
      acute coronary syndromes (ACS). In an observational prospective study we
      investigated 161 patients with ACS (acute myocardial infarction and unstable
      angina) submitted to PTCA. In 140 patients a follow-up angiography after 10 days
      was obtained. All angiograms were quantitatively evaluated by computerized
      measurements. Target vessel reocclusion and early luminal renarrowing was
      observed in 10 patients (7.1%) and 19 patients (13.6%), respectively. Using
      univariate analysis, significant risk factors (P < 0.05) for early reocclusion
      and renarrowing were diabetes mellitus (relative risk [RR] 6.1 and 5.0), arterial
      hypertension (RR 7.7 and 3.3), postprocedural lesion length > or = 2.5 mm (RR 6.8
      and 7.1), postprocedural minimal lumen diameter < or = 2.5 mm (RR 9.0 and 5.8),
      residual stenosis > or = 25% (RR 4.8 and 3.5) and absence of stents (RR 4.1 and
      3.2). Moreover, in multivariate analysis hypertension and postprocedural lesion
      length could be identified as independent risk factors for reocclusion and
      renarrowing. Diabetes mellitus was found to be an independent risk factor for
      renarrowing. CONCLUSIONS: In a consecutive series of patients with ACS undergoing
      PTCA with provisional stenting the occurrence of early target vessel reocclusion
      and luminal renarrowing is lower than previously reported for this subset of
      patients treated by PTCA alone. Adverse outcome is related to absence of stents,
      angiographic factors (residual stenosis, lesion length, minimal lumen diameter
      after procedure) and patient-related factors such as diabetes and hypertension.

PMID- 10929433
TI  - [Complete arterial revascularization of multivessel coronary disease: are
      conduits sufficient?].
AB  - BACKGROUND: Complete arterial coronary artery bypass grafting seems to be an
      alternative surgical approach in the treatment of coronary artery disease.
      Complications in the long-term follow-up due to degeneration of venous grafts may
      be reduced using arterial conduits. Prolonged operating times and increased
      trauma due to harvesting of multiple arterial grafts have been arguments for the
      conventional operative approach. We present our experience using new operative
      techniques, such as skeletonization of arterial grafts and the T-graft
      configuration. MATERIAL AND METHODS: Between 3/96 and 7/99, 405 patients with
      multiple coronary artery disease underwent complete arterial revascularization at
      our institution. The operations were performed using only two skeletonized
      grafts, both internal thoracic arteries in 105 patients (25.9%), internal
      thoracic artery and radial artery in 299 patients (73.8%) and 1 radial artery in
      1 patient (0.3%). RESULTS: In 346 patients (85.4%) a T-graft configuration was
      used. A mean of 4.1 +/- 0.9 coronary anastomoses were performed per patient. In
      hospital mortality was 2%. Sternal dehiscence or infection occurred in 0.8% of
      patients. Harvesting of the radial artery was performable with a low morbidity.
      One week postoperatively, coronary angiography showed 96.7% of coronary
      anastomoses free of stenosis > 50%. CONCLUSION: Complete arterial coronary
      revascularization using skeletonized grafts and the T-graft approach is a safe
      technique in the treatment of multiple coronary artery disease. Low perioperative
      morbidity and mortality make its usage on a routine basis possible.

PMID- 10929434
TI  - [Antegrade flow in the aorta ascendens despite aortic atresia: 2 case reports
      with retrograde coronary perfusion through coronary fistulas and sinusoids].
AB  - In aortic atresia, coronary perfusion normally occurs through retrograde blood
      flow in the ascending aorta. We report on two patients with antegrade flow in the
      ascending aorta despite aortic atresia. In one patient with hypoplastic left
      heart syndrome (aortic atresia, severe mitral stenosis), an intact interatrial
      septum/premature closure of the foramen ovale was found. While no other way of
      left atrial or ventricular decompression was found, echocardiography, angiography
      and the post-mortem examination showed left ventricular to coronary sinusoids as
      the sole pathway for systemic oxygenation. In a second patient with complex
      congenital heart disease, including aortic atresia, antegrade flow in the
      ascending aorta was through a left coronary fistula with shunt flow originating
      from the pulmonary trunk. This report describes systemic perfusion depending on
      retrograde coronary flow due to coronary-cameral (sinusoids) and coronary arterio
      venous fistulas leading to the phenomenon of antegrade blood flow in the
      ascending aorta despite aortic atresia.

PMID- 10929435
TI  - Percutaneous transluminal coronary angioplasty of left main stenosis--results of
      the German PTCA registry.
AB  - In cases with protected left main stenosis by previous bypass surgery or as an
      emergency intervention in patients presenting with acute myocardial infarction
      and cardiogenic shock, percutaneous transluminal coronary angioplasty is
      performed as an alternative treatment strategy to bypass surgery. A review of 262
      left main angioplasties revealed a procedure-related mortality in cases without
      protection of the left main coronary artery of 9.1% (4/44), in cases with
      partially protected left main stenosis by collaterals to either left coronary
      artery of 4.8% (1/21) and 0.5% (1/187) in cases with nonobstructed bypass grafts
      to either left coronary artery. Coronary angioplasty of an unprotected left main
      coronary artery, had an unacceptably high procedure-related mortality rate and
      should therefore not be performed even in cases of emergency intervention. The
      risk stratification of the procedure can be evaluated by the proposed grading of
      left main artery protection.

PMID- 10929436
TI  - [Biophysical study of coronary stents: which factors influence the dilatation and
      recoil behavior?].
AB  - In Europe more than fifty stents are currently available for the therapy of
      coronary artery disease. Nonetheless it is unknown whether material and design
      influence the stent's behavior. We have studied the recoil and dilatation
      behavior of five currently available stainless steel (316L) stents compared to
      stent prototypes made of pure titanium. Furthermore we have investigated how the
      behavior is influenced by the process of crimping. The aim of this work was to
      determine material and design characteristics, which influence the recoil and
      dilatation behavior. The 316L stents showed a homogeneous behavior (plateau
      pressure min. 1.15 +/- 0.01 atm, max. 0.26 +/- 0.03 atm, recoil min. 0.15 +/-
      0.03%, max. 0.26 +/- 0.03%). The titanium stent showed a linear response to the
      balloon expansion. This was seen in a significantly lower plateau pressure (0.43
      +/- 0.15 atm, p < 0.001). Despite the material characteristics of titanium, there
      were no significant differences in the recoil behavior (0.28 +/- 0.02%). Crimping
      leads to stent alterations which result in a significantly higher plateau
      pressure (1.9 +/- 0.07 atm vs. 2.7 +/- 0.58 atm, p < 0.001) and a reduced end
      diameter (3.6 +/- 0.02 mm vs. 3.54 +/- 0.05 mm, p < 0.005). The presented data
      show that the dilatation behavior is relying on the stent material while the
      recoil is strongly influenced by the stent design.

PMID- 10929437
TI  - [Administration of adenosine for termination of atrioventricular nodal reentry
      tachycardia: induction of atrial fibrillation with rapid conduction over an
      accessory pathway and unmasking of concomitant Wolff-Parkinson-White syndrome].
AB  - The antiarrhythmic properties of adenosine, its ultra-short half-life and the
      absence of frequent serious side effects make it a front-line agent in arrhythmia
      management, especially in the treatment of atrioventricular nodal reentrant
      tachycardia. Due to a shortening of atrial refractoriness, adenosine can
      facilitate the induction of atrial fibrillation. Life threatening tachycardias
      may result from a potential rapid conduction of atrial fibrillation over an
      accessory pathway especially if the latter one has a short antegrade refractory
      period. We report a case of a 59 year old female patient in which intravenous
      administration of adenosine during typical atrioventricular nodal reentrant
      tachycardia was followed by atrial fibrillation with rapid conduction over a
      hitherto unknown accessory pathway. After intravenous administration of adenosine
      the tachycardia was terminated successfully within 38 s. After a short period of
      asystole, spontaneous atrial fibrillation developed unmasking an antegrade
      preexcitation with subsequent rapid ventricular response (210 b/min). The three
      lead ECG showed a narrow QRS complex tachycardia. Because of spontaneous
      conversion to sinus rhythm and the absence of hemodynamic compromise there was no
      need for external cardioversion. During electrophysiological study an antidromic
      atrioventricular reentrant tachycardia was recorded over a left posteroseptal
      accessory pathway including antegrade conduction properties only. Because of its
      ultrashort half-life, serious side effects after adenosine administration are
      rare. The possibility of life threatening proarrhythmias after intravenous
      adenosine administration should be taken into consideration if the etiology of a
      paroxysmal supraventricular tachycardia is not clear and a concomitant Wolff
      Parkinson-White syndrome cannot be excluded. As with application of all
      intravenous antiarrhythmic agents, the administration of adenosine should only be
      performed if continuous ECG monitoring and cardioversion facilities are available
      and possible.

PMID- 10929438
TI  - Relationship between surface electrocardiogram characteristics and endocardial
      activation sequence in patients with typical atrial flutter.
AB  - OBJECTIVES: The relationships that exist between endocardial and surface
      electrocardiogram (ECG) activity in patients with AFl have not been
      satisfactorily delineated. The aim of the study was to determine the
      relationships that exist between the atrial endocardial activity and the surface
      ECG in patients with atrial flutter (AFl). METHODS: In 40 patients with AFl, a 64
      electrode basket catheter (BC) was deployed in the right atrium (RA). A decapolar
      catheter was inserted into the coronary sinus (CS) to record from the left
      atrium. The temporal relationship between endocardial and surface ECG activity
      was determined by means of electronic calipers. RESULTS: In counterclockwise AFl,
      the activation of the lateral wall of RA coincided with the positive deflections
      in lead I, V1 and V6 and the upstroke component in inferior leads. Plateau
      duration in lead III (121 +/- 27 ms) correlated strongly with isthmus conduction
      time (117 +/- 23 ms) (r = 0.91). Septal and left atrial conduction coincided with
      negative components in lead I, inferior leads and V6 and positive deflections in
      leads aVL and V1. In clockwise AFl, the F wave was notched in all ECG leads. The
      first component resulted from the activation of the septum and posterior wall of
      the RA. The second component was coincident with activity recorded in CS
      electrograms. The interval between the two deflections (60 +/- 18 ms) correlated
      strongly with interatrial conduction time (57 +/- 19 ms) (r = 0.84). Interatrial
      conduction interval was prolonged during AFl as compared to sinus rhythm (60 +/-
      18 ms vs 43 +/- 13 ms, p = 0.04). Activation of the lateral wall of RA coincided
      with the negative components in lead I, inferior leads and V6. CONCLUSIONS: The
      electrical activity in surface ECG closely correlates with conduction in specific
      parts of the atria. Polarity of the F wave in an ECG lead is determined by a
      resultant of opposing activities from the lateral wall of the RA and the left
      atrium.

PMID- 10929439
TI  - [Atrioventricular nodal reentry tachycardia in children: curative treatment by
      high frequency catheter ablation].
AB  - BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) is one of the
      most common forms of supraventricular tachycardia in the pediatric population.
      PATIENTS AND METHODS: 41 children with a mean age of 9.6 (3.7-16) years with
      recurrent atrioventricular nodal reentrant tachycardia (AVNRT) refractory to
      medical treatment (n = 38) and recurrent syncope (n = 3) underwent
      electrophysiologic (EP) study. In all patients dual AV-nodal physiology could be
      demonstrated during EP study and typical form of AVNRT (mean heart rate 220/min)
      could be induced by programmed atrial stimulation. A steerable 7 F ablation
      catheter was placed at the inferoparaseptal region of the tricuspid valve annulus
      close to the orifice of the coronary sinus with the intention to record a late
      fractionated local atrial electrogram during sinus rhythm. Starting at this point
      radiofrequency current (500 kHz) with a target temperature of 70 degrees C was
      delivered with the intention to ablate the slow pathway. If a slowly accelerated
      junctional rhythm (< 120/min) occurred during energy discharge, programmed atrial
      stimulation was repeated. Otherwise radiofrequency current was delivered step by
      step up to a septal position next to the tricuspid valve annulus. Slow pathway
      ablation was defined as lack of evidence of dual AV nodal pathways during
      repeated atrial stimulation. Slow pathway modulation was defined as maximal one
      atrial echoimpulse after ablation. RESULTS: The number of energy applications
      ranged from 1-19 (median 6). In 35/41 patients slow pathway ablation could be
      achieved; in six patients the slow pathway was modulated. In none of the patients
      permanent high grade AV block was observed. During follow-up (mean 4.1 years) two
      patients had a recurrent episode of AVNRT after slow pathway modulation. All
      other patients are still free of AVNRT without medical treatment. CONCLUSION:
      Selective radiofrequency current ablation/modulation of the slow pathway is a
      safe and curative treatment of AVNRT in young patients.

PMID- 10929440
TI  - [Supraventricular tachycardia in infants, children and adolescents: diagnosis,
      drug and interventional therapy].
AB  - Supraventricular tachycardias are the most frequent forms of symptomatic
      tachyarrhythmias in infants, children and adolescents. Clinical symptoms depend
      on age and underlying cardiac anatomy. Newborn babies and infants with paroxysmal
      atrioventricular reentrant tachycardias usually present with signs of congestive
      heart failure due to rapid heart rate. In older children and adolescents,
      palpitations are the leading symptom. Patients with chronic-permanent
      tachycardias (i.e., atrial ectopic tachycardia, permanent form of junctional
      reciprocating tachycardia) often develop a secondary form of dilated
      cardiomyopathy, the so-called "tachymyopathy". Adenosine has evolved as the drug
      of choice in any age group for the termination of atrioventricular reentrant
      tachycardia of any origin. In addition, it serves as a diagnostic tool in primary
      atrial tachycardias. Long-term management of atrioventricular reentrant
      tachycardia in infancy and childhood is age dependent. In newborn babies and
      infants, pharmacological therapy is advised due to the high spontaneous cessation
      rate of those tachycardias at the end of the first year of life. In contrast to
      this, the probability of spontaneous cessation of tachycardia in children > 1
      year of age is very low. Therefore, radiofrequency catheter ablation of the
      anatomical substrate of the tachycardia is a rational alternative to long-lasting
      antiarrhythmic therapy. Results in children with a structurally normal heart are
      comparable to those achieved in adults. In patients with congenital heart disease
      and supraventricular tachycardias, catheter ablation during preoperative cardiac
      catheterization is recommended. Atrial reentrant tachycardias have been
      identified as one major risk factor for late postoperative morbidity and
      mortality in young patients. Pharmacological therapy is often not sufficient to
      control the tachycardia. In addition, underlying sinus node dysfunction may be
      aggravated in a considerable portion of the patients affected. Catheter ablation
      based on conventional endocardial mapping techniques by multipolar electrode
      catheters with the aim of identifying the critical region of the reentrant
      circuit is associated with an impaired success rate and a considerable recurrence
      rate. It may be assumed that, using the modern mapping techniques currently
      available (electroanatomical mapping and non-contact mapping), results of
      radiofrequency catheter ablation of atrial reentrant tachycardias after surgical
      correction of congenital heart disease will be significantly improved within the
      next few years.

PMID- 10929442
TI  - [The diversitas captus hominum and other "storage problems"].

PMID- 10929441
TI  - [Transcoronary ablation of septal hypertrophy (TASH): a 5-year experience].
AB  - From 1991 to 1993, our group carried out extensive studies in the development of
      a new catheter-interventional concept of treatment for HOCM and suggested in 1994
      the injection of absolute ethanol into the first major septal branch using the
      common PTCA technique. This approach was first used therapeutically by Sigwart in
      London and by our group in Bielefeld. Based on rhythmologic studies of other
      authors we suggested the designation Transcoronary Ablation of Septal Hypertrophy
      (TASH). Since 1995, an estimated 1000 patients (about 600 from Germany) in some
      20 countries have been treated by this method. In 1997 a national multicenter
      TASH-registry was created by the German Cardiac Society. During the last five
      years extensive studies have been performed by different groups. Significant
      clinical and hemodynamic improvements were consistently found. This was true for
      both young and old patients, for patients with resting gradient and with
      provocable gradient. Clinical improvement (rate of improved patients about 90%)
      was seen under conditions of rest and stress, as well as during long-term follow
      up. Specifically, there was a significant decrease of functional class, a reduced
      rate of syncope, and a reduced degree of mitral insufficiency. Exercise capacity,
      oxygen uptake and the cardiac index increased, intraventricular gradient, the end
      diastolic pressure of the left ventricle and the left atrial size decreased. Also
      there was a decrease in the septal thickness with increase in the cross sectional
      area of the outflow tract and with local contraction disorder. PET examination
      showed an ablation induced local myocardial defect. There was also evidence for
      improved diastolic function. Electrophysiological and Holter monitor studies
      indicated no increased arrhythmogenicity. The prognosis seems to be improved.
      Histologically, an atypical infarct pattern was found, i.e., the common round
      cell infiltration and the fibrotic process were surrounding but not penetrating
      the alcohol induced myocardial center of necrosis. The in-hospital mortality rate
      amounts to about 1.8%. The rate of permanent total av-block after TASH is less
      than 10%. In 15% a second TASH is necessary. In summary, during the last five
      years TASH has become a promising new catheter interventional therapy for HOCM,
      which compares favorably with surgical treatment. In experienced centers it has
      become a routinely performed procedure. The indication should be limited to
      severely symptomatic patients with typical (subaortic) HOCM. Further careful
      clinical examinations after TASH are required. All patients should be enrolled
      into a registry. TASH also constitutes a new area for comprehensive clinical
      research.

PMID- 10929443
TI  - [Guideline for the joint swelling symptom--primary physician problem management
      and referral indications. German Society of Rheumatology "Quality Assurance"
      Committee].
AB  - The guideline "Joint Swelling" is addressed to primary care physicians--general
      practitioners, internists or orthopedists without special experience in
      rheumatology. It provides a framework for interviewing patients, as well as for
      physical, laboratory and imaging examinations and for selection of treatment
      appropriate to the level of primary care. Situations which call for urgent
      evaluation and criteria for referral to rheumatologists are described. The
      appendix contains comments on signs and symptoms to differentiate arthralgia from
      joint swelling and on the diagnostic value of a history of joint swelling without
      confirmation by the physician. Further recommendations for the evaluation of
      patient history and physical and technical examinations are given in a tabular
      form. The significance of laboratory and imaging procedures is discussed.

PMID- 10929444
TI  - [Scientific graduate education, sponsorship and research cooperation in the anti
      corruption law tension field--effects on members of the German Society of
      Rheumatology].

PMID- 10929445
TI  - [Apoptosis and C1q: possible explanations for the pathogenesis of systemic lupus
      erythematosus].
AB  - Dysregulation of apoptosis may play a major role in the pathogenesis of systemic
      lupus erythematosus (SLE). A defective clearance of apoptotic cells or
      inappropriately high rates of apoptosis may lead to a pathologic accumulation of
      abnormal cell material with a secondary autoimmune response. Experimental
      findings in apoptotic keratinocytes and C1q knock-out mice suggest an important
      role of C1q in the clearance of apoptotic cell material. In addition, there are
      several links between C1q and SLE: Most the patients with C1q deficiency develop
      a SLE-like syndrome. SLE itself often causes secondary C1q deficiency and
      autoantibodies to C1q are detected in almost all patients with active lupus
      nephritis. These observations suggest a central role of C1q in apoptosis and in
      the pathogenesis of SLE.

PMID- 10929446
TI  - [Therapy of glucocorticoid-induced osteoporosis with alfacalcidol/calcium and
      vitamin D/calcium].
AB  - Calcium/vitamin D supplementation is generally used as a first step treatment of
      glucocorticoid-induced osteoporosis (GIOP). The aim of this trial was to compare
      the efficacy of the D-hormone alfacalcidol with plain vitamin D in patients with
      established GIOP with or without vertebral fractures. Patients on long-term
      glucocorticoid-therapy were treated either with 1 microgram alfacalcidol plus
      5000 mg calcium (group A: n = 43) or with 1000 IU vitamin D plus 500 mg calcium
      (group B: n = 42). The two groups were not different in respect to initial
      characteristics such as age, sex distribution, concomittant diseases, bone
      mineral density (mean T-score values at lumbar spine and femoral neck: -3.29 and 
      3.25 resp.), and in the number of prevalent vertebral and non-vertebral
      fractures. During the 3 years of treatment we found a significant increase in
      lumbar spine density in group A (+2.0%, p < 0.0001), while no significant changes
      could be documented in group B at both measuring sites. After 3 years 12 new
      vertebral fractures had occurred in 10 patients of group A and 21 in 17 patients
      in group B (ns). Correspondingly we registered a significant decrease of back
      pain only in group A (p < 0.0001). We conclude that alfacalcidol treatment in
      superior to plain vitamin D in GIOP.

PMID- 10929447
TI  - [Relevance of a standardized staging study in patients with systemic vasculitis].
AB  - Primary systemic vasculitities play an important role in the differential
      diagnosis of systemic diseases. They can be classified according to newly
      developed classification criteria. In the past, systemic vasculitities were more
      diagnosed in the general phase of the disease. In the meantime limited forms can
      be diagnosed more easily. Prior to immunosuppressive therapy, a standardized
      staging-procedure is essential to define the extent of the disease. Therefore a
      program was established using methods that are easy to apply in all patients. In
      this setting the usefulness of this approach was investigated. Apart from the
      laboratory tests including antibody testing, the chest x-ray, consultation of the
      ENT specialist, ultrasound of the abdomen, and ECG were also very useful. The eye
      and neurological investigations, and the MRI of the head were of minor
      significance, but also important.

PMID- 10929448
TI  - [Effect of needle acupuncture on pain perception and functional impairment of
      patients with coxarthrosis].
AB  - OBJECTIVES: The effectiveness of acupuncture treatment in patients with
      osteoarthritis of the hip was tested. DESIGN: This is a prospective, randomized,
      controlled patient and examiner blinded clinical trial. PATIENTS AND SETTING: The
      study was performed at a university department for physical medicine and
      rehabilitation. Sixty-seven patients were separated into two treatment groups.
      INTERVENTIONS: Group 1 (treatment) had traditional needle placement and
      manipulation, whereas in group 2 (control) needles were placed away from classic
      positions and not manipulated. In both groups needles were placed within the L2
      to L5 dermatomes. Endpoints were pain (VAS), functional impairment (hip score),
      activity of daily living (ADL) and overall satisfaction before treatment, 2 weeks
      and 2 months post-intervention. RESULTS: For all endpoints there was a
      significant improvement in both groups 2 weeks and 2 months following treatment
      versus baseline, but no significant difference between the two treatment groups.
      CONCLUSIONS: We conclude from these results that needle placement in the area of
      the affected hip by itself improves symptoms of osteoarthritis. It appears to be
      less important to follow the rules of traditional acupuncture techniques.

PMID- 10929449
TI  - [A rare cause of muscle pain and elevated creatine kinase level--the paroxysmal
      non-hereditary angioedema].
AB  - Systemic capillary leak syndrome is a rare idiopathic disorder characterized by
      recurrent episodes of hypotension and hemoconcentration due to sudden transient
      extravasation of up to 70% of plasma. Less than 40 cases have appeared in the
      literature. Mortality rates 5 years after diagnosis have been reported to be up
      to 75%. Clinical findings are generalized edema and intravasal fluid deficiency.
      Laboratory features include hypoalbuminemia and extreme hemoconcentration. A
      common finding is a monoclonal gammopathy. Rare manifestation of this syndrome is
      rhabdomyolysis due to increased compartment pressure and ischemic myonecrosis.
      Early diagnosis and exclusion of other clinical disorders like rheumatic
      myopathies and myositis are critical concerning prognosis and therapy. We
      describe a 46-year-old woman with rhabdomyolysis and systemic capillary leak
      syndrome whose condition is stable for a total of 30 months under a prophylactic
      regimen with oral terbutaline plus theophylline. A brief survey of the literature
      is given.

PMID- 10929450
TI  - Drugs of abuse.

PMID- 10929451
TI  - [History of bone reconstruction].
AB  - Bone transplantation has been the subject of many experimental and clinical
      studies. Duhamel du Monceau is credited with the first scientific effort on the
      problem of osteogenesis in 1742. Leopold Ollier showed in 1861 that autografts
      are viable and recognized that separate living bone fragments without periosteum
      could live and grow in a suitable environment. In 1893, Barth published a paper
      on bone transplantation and Phemister named the process of bone reconstruction
      "creeping substitution". But it was only after Albee's book on bone graft surgery
      that bone transplantations began to be performed. In 1975, Taylor published the
      first case of free vascularized bone graft.

PMID- 10929452
TI  - [Autologous bone grafts. Anatomo-physiology, technique and actual location for
      bone reconstructions].
AB  - The authors discuss the indications for conventional nonvascularized bone grafts,
      of which the scope of utilisation has been considerably reduced since the advent
      of vascularized bone grafts. The objective of this study is to highlight the
      essential knowledge regarding the biology and biomechanics of the incorporation
      of bone grafts. The principal donor sites are examined with respect to the
      operative techniques and the advantages and disadvantages. The authors then
      derive the principal indications for conventional bone grafting and illustrate
      them with examples selected for limb reconstruction.

PMID- 10929453
TI  - [Bone vascularization. Anatomic and physiological considerations, surgical
      deductions concerning osteosynthesis procedures and vascularized bone graft].
AB  - The authors report some general considerations concerning the bony anatomy and
      the bone blood flow. They describe the vascularization of the long bones
      involving arteries, veins, capillaries and lymphatic vessels. The double systemic
      and local control of the bone blood flow is evaluated. The local factors are
      numerous: autoregulation, nervous regulation as well as humoral, metabolic and
      cellular factors. Some surgical deductions are then discussed concerning
      osteosynthesis procedures and biomechanical properties of vascularized bone
      grafts.

PMID- 10929454
TI  - [The iliac crest. Perspective on a donor site of exceptional free flaps, 20 years
      after its initial description].
AB  - The iliac crest represents the principle 'reservoir' for the cortico-spongy bone.
      After having been used for a long time in the form of a conventional graft, it
      has been the object, in the last 20 years, of increasingly sophisticated
      transfers, making it possible to extract it in vascularized form. The authors
      present the anatomical bases of these transfers, which can be conceived on four
      different vascular axes: the superficial circumflex iliac axis, which was the
      first used, the deep circumflex iliac axis, the superior gluteal axis, and the
      lateral femoral circumflex axis. After having presented the various techniques of
      extraction of the anterior and posterior crests, the authors attempted to
      delineate the indications of each variant in the reconstruction of the members
      and the cervico-facial sphere. A comparison with the fibula flap will be finally
      carried out in order to parallel the advantage and respective disadvantages of
      these two transfers.

PMID- 10929455
TI  - [The peroneal or fibular free flaps. Surgical anatomy, operative procedures and
      indications].
AB  - The microsurgical story of the fibula began 25 years ago. The author reports on
      the vascular anatomy of the fibular free flaps, particularly the osseous,
      cutaneous and muscular branches of the fibular artery and their variations. This
      surgical anatomy explains the various osseous and composite flaps that can be
      harvested on the fibular vessels. The fibular flaps harvested on the anterior
      tibial vessels are used less often. The surgical procedure is explained about the
      typical osteocutaneous peroneal flap and the many other variations. The
      indications and results are discussed according to the international literature
      and the author's experience: 42 mandibular, 12 tibial, ten femoral, three radial,
      two humeral and one nasomaxillary reconstructions. The aetiological and
      topographical particularities, various abilities of the fibular donor site,
      preoperative strategy, bone implantation and contention, vascular anastomosis and
      delays of consolidation are analysed for each recipient site. The advantages and
      disadvantages of these fibular flaps are then discussed. Finally, the present and
      future associated procedures are evoked.

PMID- 10929456
TI  - [The scapula: a preferred donor site for a free flaps or pedicles transfer].
AB  - The authors present all the possibilities that the scapula can offer as a donor
      site for bone. After having reviewed the potential for acromial transfer on a
      pedicled trapezial flap, they summarise the anatomical basis for the transfer of
      the lateral border. There are two systems of vascular supply, one based on the
      circumflex scapular vessels described by Teot and the other based on the vessels
      of the angle of the scapula described by Deraemacker. This dual blood supply
      forms a very rich anastomosis with a predominant periosteal supply that allows
      for multiple osteotomies to be made. The technique of harvesting and the
      indications are highlighted as well as an iconography, which presents the
      principle forms of reconstruction that have been described until today. The
      authors support the use of the pedicled transfer of the lateral border, which is
      poorly known and above all poorly used. Their experience in five consecutive
      clinical cases demonstrates all the potential of this technique for humeral
      reconstruction. As a microsurgical transfer, however, the principal advantage of
      using the inferior scapular axis is offset by a few drawbacks, the principal one
      being the difficulty of dissection. Its main indication as a free flap is in the
      maxillofacial surgery where it allows very precise reconstructions of the
      mandible, the palate or the maxillozygomatic region.

PMID- 10929457
TI  - [The technique and location of secondary donor sites of vascularized bone grafts
      in the therapeutic arsenal of the plastic surgeon].
AB  - Most of the donor sites for conventional bone grafts can also provide
      vascularised bone grafts. Increased progress in vascular research has enabled the
      harvesting of grafts that are increasingly reliable and versatile. This work does
      not give emphasis to classic vascularised bone transfers like the iliac crest,
      the fibula or the lateral border of the scapula but highlights 'secondary' sites
      which are often underutilized. Several donor areas are studied; the upper limb
      including the clavicle, the lower limb, the thorax and the cranium. The hands and
      toes, which constitute a specific entity, are excluded. In each chapter the
      authors have emphasised the fundamental points relating to the anatomy, the
      technique of harvesting and the indications.

PMID- 10929458
TI  - [Vascularized bone grafts in children. Specifics and indications].
AB  - The authors report on the vascularized bone grafts used in children. Some of them
      are the same as those used in adults, like the fibula free flap. Others are
      growth plate transfers as the proximal fibular epiphysis, the iliac crest or the
      lateral scapular crest. Finally, other transfers are periosteal vascularized
      grafts. The indications and results are discussed concerning the congenital
      pseudarthrosis of the tibia (43 cases treated by the first author), the
      congenital pseudarthrosis of the forearm, the tumors of the limb and the post
      traumatic defects. The specific indications in children are the microsurgical
      growth plate transfers, especially the epiphyseal growth fibula for the upper
      limb and the iliac crest for the lower limb.

PMID- 10929459
TI  - [One-stage emergency treatment of open tibial shaft fractures with bone loss.
      Specifics and indications].
AB  - OBJECTIVES: The purpose of this study was to report our experience in the
      reconstruction of severe tibial shaft fractures in emergency treatment. PATIENTS:
      Five male patients were admitted to the emergency room with a grade IIIB open
      tibial shaft fracture with bone loss, one patient with a grade IIIA open tibial
      fracture with massive articular bone loss and one patient with a grade IIIC open
      tibial fracture. INTERVENTION: Primary one-stage management was the same for the
      five patients with a grade IIIB: debridement, stabilization by locked
      intramedullary nailing, bone grafting from iliac crest. Skin loss was covered in
      the same operative time using free muscle flaps (four latissimus dorsi, one
      gracilis). For the patient with massive articular and diaphyseal bone loss, a
      vascularized fibula transfer with arthrodesis was performed one day after the
      trauma. For the patient with grade IIIC open tibial fracture, a shortening was
      performed in emergency treatment. RESULTS: The average follow-up was 21 months
      (range: eight months to 3.5 years). Partial weight-bearing was started at three
      months and the time of full weight-bearing was five months after the trauma. No
      angular complication and no non-union were observed. We noted one superficial
      infection without osteitis. All fractures healed within five to ten months (mean:
      8.5 months). At the last follow-up, ankle and knee motion was normal and no pain
      was noted, except for the patient who had an arthrodesis and another who had
      associated lesions. CONCLUSION: We think that "aggressive" emergency management
      for severe open tibial fractures gives good results. It significantly reduces
      tissue loss from infection and improves healing and rehabilitation times.

PMID- 10929460
TI  - [Reconstruction of post-traumatic diaphyseal bone loss by segmental bone
      transfer].
AB  - Until the beginning of the 1980s, reconstruction of major post-traumatic
      diaphyseal bone loss as an alternative to amputation was possible only by massive
      autologous bone grafts. Such a technique was limited by the amount of available
      bone required for grafting. Ilizarov explained the distraction osteogenesis
      principle and designed a circular external fixation material that was suitable
      for compression-extension. He described the concept of segmental bone transfer,
      which allows bone regeneration to take place within the actual injured limb. Our
      present experience is based on the literature and the study of 12 cases. All
      patients presented with significant post-traumatic tibial bone loss ranging from
      45 to 145 mm. In this article, we discuss the indications, benefits and risks of
      such a technique compared to classic methods. Mainly indicated in patients who
      have sustained significant bone loss, bone transfer is the method of choice for
      preserving bone stock and correcting limb discrepancy, although it does not
      reduce consolidation time. Moreover, circular external fixations are often poorly
      tolerated and may be replaced by unilateral devices that are easier to install.

PMID- 10929461
TI  - [Reconstruction of the long bones by the induced membrane and spongy autograft].
AB  - In the reported series of 35 cases bone reconstruction of large diaphyseal
      defects was performed in two stages. The first stage was the insertion into the
      defect of a cement spacer which was responsible for the formation of a
      pseudosynovial membrane. The second stage was the reconstruction of the defect by
      a huge fresh autologous cancellous bone graft. The membrane induced by the spacer
      prevents the resorption of the graft and favors its vascularity and its
      corticalisation. In weight bearing diaphyseal segments the normal walking was
      possible at 8.5 months on average. The length of the reconstructed defects was 4
      to 25 cm.

PMID- 10929462
TI  - [Bone allografts in orthopedic surgery: current concepts].
AB  - In the last decade, indications for bone allografting in orthopedic surgery have
      progressively increased, related to, on the one part, treatment of benign or
      malignant tumors, but, on another (major) part, to treatment of major bone
      defects due to loosening of hip or knee total prostheses. In France, legislation
      and control concerning donated human tissues, safety precautions, and the uses
      for human tissues have been greatly modified over the last few years. The authors
      describe the various obligations implicated by these activities and the
      consequences for tissue banks and surgeons; They describe different processes for
      bone inactivation and their action on allograft mechanical properties, or the
      biological capability for integration to the host bone. The authors then discuss
      different current techniques for bone stock reconstruction and the results in
      prosthetic or tumoral surgery, as well as their consequences on current surgical
      indications. In conclusion, they emphasize the optimal conditions for the success
      of allografts in orthopedic use: stability of the host bone-graft junction,
      vitality of the bone support, and a favourable mode of constraint of the graft,
      which have to be protected by osteosynthesis, but should not, however, miss
      partial bearing.

PMID- 10929463
TI  - [Biomaterials and osseous regeneration].
AB  - The autologous bone graft is commonly used for the repair of bony defects, but
      its resorption is unpredictable, and there is an inherent morbidity of the donor
      site. There is a wide range of biomaterials that could be used as bone
      substitutes, depending on their bioactivity. Among bioactive materials,
      bioglasses present a linkage between their reactive surface and the adjacent bone
      although they cannot be colonized by bony ingrowth, moreover their fragility and
      resorption as particles limit their use. The osteoconductive biomaterials are
      either represented by the synthetized ceramics, such as hydroxyapatite (HA) or
      tricalcium phosphate (TCP), or either natural coral and the derived biomaterials
      of bony matrix. Coral exoskeleton or TCP are highly resorbable, but pure HA is
      only slightly. Bony ingrowth in osteoconductive materials is limited to the
      periphery of the implant which does not make it suitable for the repair of large
      defects. Research is focused on the adjunction of a biologically active substance
      to the osteoconductive matrix in order to enhance bony ingrowth. Osteoinductive
      materials such as bone growth factors in combination with a carrier can promote
      bone healing, especially when bone morphogenetic protein (BMP) is used.
      Nevertheless, even if their efficacy is demonstrated, their inocuity has not been
      totally confirmed. Furthermore, the dose used are far superior than in the
      physiological pathways. Hybrid biomaterials combine an osteoconductive carrier
      with bone marrow cells. Bone cell cultures could amplify to almost any extent the
      number of osteogenic cells for such a biomaterial. Bone substitutes will
      certainly be used in the future to repair bony defects.

PMID- 10929464
TI  - [Engineering of osseous cells and bioartificial tissues].
AB  - The association of osteogenic stem cells to a synthetic carrier makes possible
      the elaboration of bioartificial tissue. Numerous phosphocalcic ceramics does not
      trigger a foreign body reaction when implanted in bone tissue and thus, a number
      of materials are available osteogenic stem cell carriers to replace the bone
      tissue. Several methods can be used to harvest these cells. Their multiplication
      in vitro can lead to the appearance of anomalies of their metabolism or their
      karyotype. The culture method also seems to have a major influence on their
      appearance. The presence of these anomalies could explain the variability of
      results in terms of bone extracellular matrix synthesis after cell
      reimplantation. The surgical technique used for the implantation is also of
      influence. A method suppressing the in vitro period has been developed to avoid
      any cell metabolism modification. This method allows for a very reproducible bone
      synthesis in ectopic site. The availability of human embryonic stem cells could
      help to develop cell graft techniques for bone reconstruction.

PMID- 10929466
TI  - [Bone reconstruction. Synthesis of procedures and indications].

PMID- 10929465
TI  - [Facial bone reconstruction. Review of particularities and procedures].
AB  - The authors report the particularities of the cranio-maxillofacial skeleton and
      the aims of the reconstruction procedures: osteogenesis, osteoconduction,
      osteoinduction. They review the various procedures, their abilities, some
      technical notes, their advantages and disadvantages. They analyse in order:
      classical bone autografts, pedicled bone flaps (arterio-osseous, fascio-osseous,
      myo-osseous flaps), free bone flaps, classical and pedicled periosteal
      transplantations. They also describe the mechanical and biological procedures of
      bone stimulation: bone distraction, guided bone regeneration, bone growth
      factors, and the biomaterials, especially coral and enosseous implants. They
      conclude that, in facial reconstruction, the best material is the autologous bone
      membranous and vascularized.

PMID- 10929467
TI  - The meaning of health to the low-income patients in a primary care center.

PMID- 10929468
TI  - Health services for immigrant children: opportunities under Title XXI.
AB  - This article notes the health care risks for immigrant children and describes
      recent restrictions on their ability to apply for Medicaid. It is reasonable to
      estimate that by the year 2001, there could be as many as two million immigrant
      children in the United States who are ineligible for Medicaid simply due to their
      immigration status. The article also describes the opportunities under the new
      federal law, Title XXI of the Social Security Act, which enables states to
      develop health care programs specifically for low-income immigrant children who
      are ineligible for Medicaid. Pediatricians, advocates for children, and health
      care providers who serve immigrant communities can use their knowledge of the
      opportunities in this new law to work with state lawmakers and health policy
      officials to help provide services to needy immigrant children.

PMID- 10929469
TI  - Depressive symptoms in rural West Virginia: labor market and health services
      correlates.
AB  - The prevalence and socioeconomic correlates of depressive symptoms in rural West
      Virginia were assessed. A random-digit-dialed telephone interview was
      administered to a community-dwelling sample of adults, ages 18 to 64, residing in
      the 40 rural counties of the Appalachian State of West Virginia. Depressive
      symptoms were measured with the Center for Epidemiologic Studies Depression Scale
      (CES-D). Overall rates of depressive symptoms were substantially higher than in
      the nation as a whole. Gender differences were lower than expected due to a high
      rate of depressive symptoms among men. Depressive symptoms were inversely
      associated with higher socioeconomic position. One-third of those who described
      themselves in "good mental health" reported depressive symptoms. About half who
      reported depressive symptoms had never seen a mental health professional or a
      physician for mental health problems. Efforts to increase awareness and access to
      mental health services are needed to promote the mental health of rural West
      Virginian populations.

PMID- 10929470
TI  - Later-stage cancer in relation to medically underserved areas in Connecticut.
AB  - Health status indicators, including advanced stage at diagnosis of cancer, have
      been proposed as indicators of health care access and quality to be considered in
      revising the definition of medically underserved areas (MUAs). Using the
      population-based Connecticut Tumor Registry, "outlier" census tracts were defined
      as those that had a high proportion of breast, colorectal, or cervical cancer
      diagnosed at later stage, relative to all tracts in the state. In the six
      Connecticut cities that had MUAs, MUAs comprised the majority of outlier tracts,
      but non-MUA outliers were often located on the fringes of MUAs. The findings are
      discussed in relation to revising the criteria for defining MUAs and to targeting
      interventions for early detection of cancer in urban areas.

PMID- 10929471
TI  - Linking African American mothers across life stage and station through
      photovoice.
AB  - Homeless young African American women and low-income, elderly African American
      women have housing needs specific to their age cohorts, yet they also have
      parallel and complementary housing, health, and personal needs. The young
      struggle to afford decent housing, while the old may have difficulty maintaining
      their homes. In this pilot study, intergenerational contact was established
      between young homeless women and elderly independently housed women through
      photovoice. Over six months, five African American women discussed photographs
      they had taken that focused on their current living arrangements and activities.
      Although the women spanned three generations, had different life experiences, and
      resided in a variety of home settings, the sharing of photographs revealed many
      commonalities. In the process of discussing photographs, the women established
      mutual respect, exercised reciprocal affirmation, and built alliances. The
      preliminary study is preparatory to exploring the feasibility of establishing
      house-sharing arrangements for mutual assistance between these cohorts.

PMID- 10929472
TI  - Collaborative inquiry with low-income Latina women.
AB  - Collaborative inquiry is a form of research in which researchers and participants
      work collaboratively as partners. The purpose of this paper is to demonstrate the
      process of collaborative inquiry through an example of a longitudinal, community
      based study conducted over a six-year period. The research program focused on HIV
      education, counseling, and antibody testing with low-income Latina women
      attending a nutrition program for women, infants, and children (WIC) in Los
      Angeles. Collaborative, community-based inquiry emerges from the community and
      uses members of the targeted group to design the program, convey the message, act
      as advocates, evaluate the outcomes of the program, and disseminate research
      findings. The goal is empowerment and emancipation of both participants and
      researchers. Five areas in the conduct of community-based collaborative inquiry
      are demonstrated here: program design, implementation, evaluation, dissemination
      of the results of the program, and empowerment and emancipation.

PMID- 10929473
TI  - Equity concerns with the use of hospital services by the medically vulnerable.
AB  - This study assessed distributional inequities in access to care among a
      representative sample of adults residing in Oklahoma. Inequities were identified
      by comparing the medically vulnerable to the less vulnerable with respect to
      their use or nonuse of hospital care and, among those admitted, the number of
      days of care consumed. The behavioral model was employed to guide the analysis
      and the development of hypotheses. Controlling for need, enabling, and
      predisposing factors, the results indicate that the use of service by the poor,
      the elderly who lack supplemental insurance, and the uninsured is incongruent
      with their health status and that current methods of financing care may
      contribute to distributional inequities. The implications of these findings are
      discussed in the context of options that may improve access to care by the
      medically vulnerable.

PMID- 10929475
TI  - [In Process Citation]

PMID- 10929474
TI  - [Counseling and prevention are essential. Tropical illness in the Mediterranean].

PMID- 10929476
TI  - [Diagnosis of alcoholism: CDT test does help].

PMID- 10929477
TI  - [Nephropathies are treated too late. 10,000 dialysis patients could have healthy
      kidneys].

PMID- 10929478
TI  - [Diagnosis of acute appendicitis. Is physical examination enough to reach a
      surgical decision?].
AB  - In the large majority of cases, acute appendicitis can be diagnosed on the basis
      of the medical history and the patient's symptoms. Urine should be drawn from
      every patient for urinstix and bacteriological testing, as well as blood for a
      blood count, electrolytes and coagulation parameters. A US should be performed,
      in particular to exclude possible other diagnoses. Women should be examined by a
      gynecologist. Once the diagnosis has been established, the patient must be sent
      for surgery without delay. Should there be reason for doubt, further diagnostic
      measures (in particular CT) should be carried out as permitted by the urgency of
      the case. In life-threatening situations, laparoscopy should be done immediately,
      and preparations made for laparotomy should this be necessary. If the symptoms
      are such that a wait-and-see attitude is justified, continued observation and
      follow-up examinations are recommended. The diagnosis of acute appendicitis can
      be difficult, and every patient who rouses relevant suspicion, should be seen by
      a surgeon.

PMID- 10929479
TI  - [Ultrasound first in acute appendix? Unnecessary laparotomies can often be
      avoided].
AB  - Acute appendicitis is one of the most common causes of acute abdomen. Prospective
      studies have shown the overall accuracy of the clinical diagnosis to be not more
      than 70-78% in suspected appendicitis, with a correspondingly high rate of 20-25%
      unnecessary laparotomies. High-resolution ultrasonography (US) is a readily
      available, radiation-free noninvasive diagnostic modality that enables
      visualization of the inflamed appendix and a variety of relevant diseases in the
      differential diagnostic work-up. Prospective studies have shown that the overall
      accuracy of US in acute appendicitis ranges between 86 and 87% (sensitivity 75
      92%, specificity 92-100%), with positive and negative predictive values of 89
      96%, respectively. In experienced hands, US has significantly improved the
      diagnostic accuracy in suspected appendicitis, while halving the negative
      laparotomy rate to 8-15%. Since, however, a low percentage of false-negative US
      explorations due, for example, to accumulation of bowel gas or obesity, final
      therapeutic decisions be based on a careful consideration of US findings together
      with history, symptoms and clinical findings.

PMID- 10929480
TI  - [Targeted practice service for the patient. Help with smoking cessation].

PMID- 10929481
TI  - [Thrombosis ABC, 17: Pregnancy. How to minimize the risk of thrombosis in
      thrombophilia].

PMID- 10929482
TI  - [Lipid profile in 4 minutes. Impressing your coronary heart disease patients].

PMID- 10929483
TI  - [Doxazosin GITS versus regular doxazosin in benign prostatic hyperplasia.
      Restoring urine flow and sexual function more easily].

PMID- 10929484
TI  - [Diagnostic quiz. Painful liver. Budd-Chiari syndrome].

PMID- 10929485
TI  - [In Process Citation]

PMID- 10929486
TI  - [Most recent study results show: the bisphosphonate alendronate works more
      rapidly than previously assumed].

PMID- 10929487
TI  - [Short-term intervention in ulcer and reflux. New acid blocker halves duration of
      therapy].

PMID- 10929489
TI  - [More protection for the kidneys if diabetic patients. PROSIT project shows the
      first successes].

PMID- 10929488
TI  - [Heart failure. Beta blockers on increasingly more solid ground].

PMID- 10929490
TI  - [Calcium antagonists in the overweight hypertensive patient. Secondarily also
      dealing with foam cells].

PMID- 10929491
TI  - [Risk of complications in the diabetic patient. Postprandial blood glucose peaks
      as deciding factor].

PMID- 10929492
TI  - [A new bisphosphonate. A vertebral body fracture seldom remains alone].

PMID- 10929493
TI  - [9. Heart failure: old diagnosis--new strategies].

PMID- 10929494
TI  - [The regionalization of third-level tuberculosis laboratories is urgently needed
      in Mexico].

PMID- 10929495
TI  - [Comments on the article entitled Cardiovascular risk factors and carotid
      atherosclerosis detected with ultrasonography].

PMID- 10929496
TI  - [Comment on the article entitled Prevalence of hepatitis B and C in blood
      donors].

PMID- 10929497
TI  - [Training future dentists, according to today's needs].

PMID- 10929498
TI  - [Trends of hospital infections at an oncology center, 1986-1996].
AB  - OBJECTIVE: To describe the results of ten years of nosocomial infection (NI)
      surveillance in an oncology center. MATERIAL AND METHODS: This is a descriptive
      study of the Infection Control and Surveillance Program Committee at the
      Instituto Nacional de Cancerologia, conducted in 1997. From June 1986 to December
      1996, we surveyed 62,733 hospital discharge records. Criteria used to classify
      nosocomial infections were those outlined in 1972 by the Centers for Disease
      Control and Prevention, Atlanta (GA). Survey data were collected through review
      of microbiology chart records and of hospital chart records of febrile patients,
      patients receiving antibiotics, and patients visited after surgery. We calculated
      the rates of NI as the number of infections/100 discharges. RESULTS: The rate of
      NI per 100 discharges was 4.4 in 1986, 7.7 in 1987, 8.1 in 1988, 5.9 in 1989, 4.6
      in 1990, 5.1 in 1991, 4.3 in 1992, 5.4 in 1993, 7.6 in 1994, 7.1 in 1995 and 8.5
      in 1996. Escherichia coli was the microorganism most frequently isolated. From
      1987, an increase of almost seven times in fungi isolations as well as
      enterococci was observed. CONCLUSIONS: An increasing trend in NI rates was
      observed in the last four years, probably related to multiple factors such as
      improved surveillance (better reporting) and a real increase in the frequency of
      NI.

PMID- 10929499
TI  - [Usefulness of geographic analysis in the study of deaths caused by motor vehicle
      injuries].
AB  - OBJECTIVE: The purpose of this paper is to demonstrate the usefulness of
      geographic analysis to assess the distribution of fatal pedestrian run-over
      injuries. MATERIAL AND METHODS: Cross-sectional study of mortality due to
      pedestrian run-over injuries was conducted in year 2000. Data were abstracted
      from death certificates of pedestrians who died due to run-over injuries in
      Mexico City, during 1994-1997 (International Classification of Diseases code
      E814.7). Crude mortality rates were obtained by political district and gender.
      Georeferenced mortality data were mapped by different levels of aggregation,
      using the software program Map-Info. RESULTS: A total of 3,687 pedestrian
      fatalities were reported; 71% of them were Mexico City residents. Only 1,152
      deaths (43.5%) were georeferenced, due to availability of the exact place of the
      event occurrence. Results by level of aggregation were: by political district
      level; Milpa Alta, Cuajimalpa and Cuauhtemoc had the highest death rates (23 per
      100,000). At the next level (neighborhoods or colonias), ten colonias had over
      nine cases; and at the street level, one point at La Venta in Cuajimalpa
      presented 25 death cases due to pedestrian run-over injuries. CONCLUSIONS: This
      kind of analysis helps us to display the spatial relationship between pedestrian
      run-over sites and other city landmarks, to advance in the study and prevention
      of pedestrian run-over deaths.

PMID- 10929500
TI  - [Fluorosis in primary dentition in a region with endemic water fluoride].
AB  - OBJECTIVE: The aim of the present study was to estimate the prevalence of dental
      fluorosis in primary dentition of a San Luis Potosi children population, and its
      association to fluoride concentration in drinking water and urine. An additional
      objective was, to develop, validate, and test a specific index for dental
      fluorosis in primary dentition. MATERIAL AND METHODS: From May 1997, to January
      1999, we conducted a cross-sectional study to assess the prevalence of dental
      fluorosis in primary dentition. Study subjects were 100 children aged 3-6 years,
      selected at random from three kindergartens in three risk areas of San Luis
      Potosi. The specific index of dental fluorosis for primary dentition (Dental
      Fluorosis for Primary Dentition Index--DFPDI) was validated by estimating
      fluoride concentrations in enamel of teeth with and without dental fluorosis. The
      Kruskal-Wallis test was used to assess the association between fluoride
      concentrations in drinking water and urine, with dental fluorosis; the
      association between risk area and dental fluorosis was assessed with the Mantel
      Haenszel chi 2 test. RESULTS: The prevalence of dental fluorosis in primary
      dentition was 78%; primary molars were most affected in both maxillae and the
      predominant color was a non-glossy white appearance. We found a strong direct
      correlation (r = 0.93) between fluoride concentrations in primary teeth and the
      DFPDI. Associations were found between fluoride concentrations of drinking water
      and urine, with dental fluorosis (Kruskal-Wallis p = 0.00001), and between risk
      area and dental fluorosis (Mantel-Haenszel chi 2 p = 0.00001). CONCLUSIONS: DFPDI
      allowed adequate identification and grading of dental fluorosis in primary
      dentition. It is important to detect the initial toxic effects of fluoride
      exposure to predict dental fluorosis in permanent dentition and skeletal
      fluorosis.

PMID- 10929502
TI  - Identity and experience: a study of selected female physicians in five provincial
      states of Mexico.
AB  - The aim of this paper is to analyse the identity(ies) and experiences of a
      selected group of female physicians in five provincial states of Mexico. In the
      last 30 years the number of female physicians in Mexico has grown considerably
      and yet little is known about these women. Data for this work were drawn from two
      in-depth interviews with 99 female physicians during 1995-1996. In addition,
      physicians were asked to complete a personal diary to illustrate the nature of
      their daily experiences over a three-month period; the gap between the two
      interviews. Analysis reveals female physician identity is shaped by Mexican
      health care service structures, personal characteristics and goals, and career
      development choices and opportunities. Association with particular spaces and
      places influences female physician career development and identity. The multiple
      identities of these professional women and their lived experiences can result in
      various pressures and tensions in family and career life. As a result these women
      make choices about career development; some reassess their career goals given
      their family and household circumstances and thus their career development may
      appear to be constrained. The paper concludes by suggesting that changes in
      Mexican health institutions and the science of medicine may lead to changes in
      female physician identity.

PMID- 10929501
TI  - [Hypersensitivity pneumonitis in Mexico City].
AB  - OBJECTIVE: To investigate the association between the urban area of origin of
      patients and the prevalence of hypersensitivity pneumonitis (HP), induced by
      avian antigens. MATERIAL AND METHODS: A case-control study was conducted in 1999
      at the National Institute of Respiratory Diseases (NIRD). Cases were 109
      consecutive HP patients and controls were 184 patients: 39 with idiopathic
      pulmonary fibrosis (IPF), 63 with pulmonary tuberculosis (PTB), and 82 with
      asthma. Mexico City and surrounding counties (SC) were divided into 5
      geographical areas: 1) Downtown; 2) North-East (NE); 3) South-East (SE); 4) North
      West (NW) and 5) South-West (SW). Statistical analysis consisted of calculation
      of disease prevalence by urban area; associations were assessed with odds ratios
      and 95% confidence intervals. Multivariate analysis with multiple logistic
      regression was performed to adjust for age, gender and socioeconomic level.
      RESULTS: Eighty HP cases were located in the NE southernmost and SE northernmost
      areas of Mexico City (48 and 32, respectively) (OR = 3.86; 95% CI 2.17-6.96).
      Thirty-six controls with asthma came from the SW area, (where NIRD is located) (p
      < 0.05), and four from SC. Controls with PTB and IPF were scattered throughout
      the study area. CONCLUSIONS: The NE southernmost and SE northernmost areas were
      associated with HP. The cause of HP may not be geographical; a garbage dump used
      to be located in this area, suggesting that exposure to organic particles might
      contribute to the development of HP in susceptible individuals.

PMID- 10929503
TI  - [Home-making responsibilities and health of working women].
AB  - OBJECTIVE: To analyze the relationship between the distribution of home-making
      responsibilities and perceived mental and physical health in working women.
      MATERIAL AND METHODS: A cross-sectional study was conducted between September
      1994 and October 1995, in Caracas, Venezuela. A total of 260 university teachers
      were surveyed on home-making management and activities. Statistical analysis
      consisted of central tendency measures, analysis of variance and hierarchical
      multiple regression. RESULTS: Considering the distribution of home-making
      responsibilities, it was found that women participated more in home-making
      management and planning and that they received support from their partner in
      those tasks related to home-making. Those women who perceived higher overload in
      home-tasks reported also higher levels of anxiety, depression and a lower self
      esteem. CONCLUSIONS: These results indicate the negative effects of household
      labor on mental health in working women.

PMID- 10929505
TI  - [Cohort studies. Methodology, biases, and application].

PMID- 10929504
TI  - [Antimicrobial resistance characteristics of clinical isolates of Streptococcus
      pyogenes].
AB  - OBJECTIVE: To determine the antibiotic susceptibility of recent isolates of
      Streptococcus pyogenes and to evaluate the prevalence of macrolide-resistant
      phenotypes. MATERIAL AND METHODS: In 1999, we conducted a cross-sectional study
      at Mexico Children's Hospital "Federico Gomez", to analyze one hundred strains of
      S. pyogenes isolated from 1992 to 1998, in children with uncomplicated
      pharyngotonsillitis. Strains were frozen at the bacteriology lab until they were
      analyzed. Strains were tested for susceptibility against some beta-lactams,
      macrolides and clindamycin. Double-disk testing was carried out to evaluate
      erythromycin-resistant phenotypes. Data are presented using central tendency
      measures. RESULTS: All tested strains were not resistant to beta-lactams and
      clindamycin; 16% of the strains were resistant to macrolides and all of them
      belonged to phenotype M. CONCLUSIONS: Susceptibility testing is recommended to
      identify possible changes in antibiotic resistance to streptococci.

PMID- 10929506
TI  - [Survival analysis. Application in a sample of women with cervical cancer in
      Mexico].

PMID- 10929508
TI  - [In Process Citation]

PMID- 10929507
TI  - [Health resources at units of the Health Secretariat, 1999].

PMID- 10929509
TI  - [The results and conclusions from the medical support of the troops in armed
      conflicts].

PMID- 10929510
TI  - [The outlook for the improvement of sanatorium-health resort treatment].

PMID- 10929512
TI  - [The medical consequences of earthquakes and the organization of their
      elimination].

PMID- 10929511
TI  - [Hypertension: the organizational and methodological aspects of military medical
      expertise].

PMID- 10929513
TI  - [Questions in the surgical treatment of focal liver lesions].

PMID- 10929514
TI  - [The use of artificial neuronal networks in the treatment of peptic ulcer].
AB  - Today the use of artificial neuronic nets (ANN) is the most perspective method in
      the prediction of clinical course and in the choice of correct therapeutic
      tactics. The experimental complex "Axon" with the software was created in the
      hospital that permitted to predict the course if gastric and duodenal ulcers. We
      introduced the data of 909 patients that contained the anamnesis, results of
      objective examination and late results of the treatment. These data has become
      the base for training and formation of ANN similar to the structure of human
      cerebral cortex. Having received the information about a new patient and using
      the previous experience of therapy of 909 patients mentioned above the trained
      ANN gives an accurate information concerning this patient. It is presented in the
      form of protocol of prognosis of ulcer clinical course, the probability of
      complication development, the results of conservative and surgical treatment. The
      protocol includes the conclusion with recommendations on the choice of
      therapeutic tactics.

PMID- 10929515
TI  - [The cardiovascular manifestations of carcinoid tumors].

PMID- 10929516
TI  - [The rehabilitation of middle-aged and elderly patients in a pulmonary
      tuberculosis clinic].
AB  - In respect of other age groups the number of elderly and old patients constantly
      increases and today it constitutes the 5th part of population in many countries.
      That's why the "ageing" of tuberculosis is a natural process. The urgency of the
      problem of pulmonary tuberculosis in the elderly and senile age is determined by
      the high epidemiologic indices of disease incidence, by the difficulties of
      diagnosis and clinical course and by the peculiarities of rehabilitative measures
      in the patients of these age groups. The article deals with some medical aspects
      of the hospital period of rehabilitation in the patients with pulmonary
      tuberculosis. These aspects concern the new methodological approaches to the
      evaluation of therapeutic efficiency and to the formation of patient populations
      of the elderly and senile age, who need the restorative treatment under
      conditions of the specialized rehabilitative department.

PMID- 10929517
TI  - [A trial of treating depressive states with cipramil].

PMID- 10929518
TI  - [The Created in Russia exhibition].

PMID- 10929519
TI  - [Portable high-frequency electrosurgical apparatus].

PMID- 10929520
TI  - [The Aqua-Dialysis systems for water purification].

PMID- 10929521
TI  - [The demonstration of a hepatitis syndrome by an index of vitamin B2 excretion].

PMID- 10929522
TI  - [Military ecology and military hygiene: the concept of an interaction].
AB  - At the modern level of society development, on the one hand its Armed Forces are
      the object that requires the defense from unfavourable effect of environmental
      factors, on the other hand they are potential source of ecology worsening. The
      problem of ensuring ecological safety in the army and navy becomes urgent. In
      order to solve this problem first of all it is necessary to develop the
      conceptual bases of military ecology. Among all medical sciences the military
      hygiene by purpose, tasks, subject and objects is the most close to military
      ecology.

PMID- 10929523
TI  - [The subject of military medicine on Russian medals].

PMID- 10929524
TI  - Modified Cretan Mediterranean diet in the prevention of coronary heart disease
      and cancer.

PMID- 10929525
TI  - What is so special about the traditional diet of Greece. The scientific evidence.

PMID- 10929526
TI  - Antioxidants in Mediterranean diets.

PMID- 10929527
TI  - Olive oil.

PMID- 10929528
TI  - Dietary fats of European countries in the Mediterranean area.

PMID- 10929529
TI  - Protection from cardiovascular disease by wine and its derived products.
      Epidemiological evidence and biological mechanisms.

PMID- 10929530
TI  - The Mediterranean diet in Italy.

PMID- 10929531
TI  - Dietary habits and nutritional status in Spain.

PMID- 10929532
TI  - Mediterranean diets in the Maghreb.

PMID- 10929534
TI  - [XX Forum on Cancer. Paris, France, 6-8 June 2000. Abstracts].

PMID- 10929535
TI  - [The indications for and results of video thoracoscopic sympathectomy].
AB  - BACKGROUND AND OBJECTIVES: Thoracoscopic sympathectomy, for years an effective
      way to treat mainly palmar and axilla hyperhidrosis, experienced a revival since
      the application of the principles of minimally invasive surgery. We report the
      personal experiences of three surgeons with this technique, as well as patients'
      view of the outcome. PATIENTS AND METHODS: Between January 1990 and November
      1997, 73 procedures were performed in 43 patients (23 males, 20 females, mean age
      38.1 years, range 15-82 years), and the outcome was prospectively studied. Palmar
      hyperhidrosis without axilla symptoms was the indication for the operation in 27
      patients (54 sympathectomies), Raynaud's syndrome in 15 (18 sympathectomies), and
      causalgia in one. Thoracic ganglia 2-4 were always completely resected.
      Perioperative morbidity as well as patient satisfaction in the long-term course
      (standardized interview) 25.8 (1-77) months postoperatively were assessed.
      RESULTS: The complication rate in all 73 sympathectomies was 8.2%. Only two
      severe incidents were observed: in one patient intermittent Horner's syndrome
      (1.4%) occurred, and in another severe bleeding required conversion to open
      surgery (1.4%). Both complications occurred in the early study phase. The initial
      success rate in all 27 patients with hyperhidrosis was 100%. In 30% of these
      cases a mild partial relapse was observed, which did not interfere with their
      daily activities. 53% of the patients reported compensatory and 23% gustatory
      sweating. 9% would have refused the operation, had they known these side effects.
      In all patients with Raynaud's disease the ulcerations healed completely. At the
      time of the interview, two patients (13%) complained of painless relapses. They
      too stated that they had refused the operation, if they had known about the
      relapses. CONCLUSIONS: Even in the longer-term course, thoracoscopic
      sympathectomy is rated subjectively successful by 93% of patients after treatment
      of hyperhidrosis of the upper extremities, and by 87% of patients after treatment
      of Raynaud's disease, despite some untoward effects and partial relapses.

PMID- 10929536
TI  - [The treatment of iatrogenic spurious aneurysm of the femoral artery by direct
      thrombin injection].
AB  - BACKGROUND AND OBJECTIVE: After percutaneous catheter introduction a false
      aneurysm occasionally develops at the site of puncture. This has been treated
      either surgically or, more recently, by ultrasound-guided compression. A new
      method has been tried in which the false aneurysm is thrombosed by injecting
      thrombin into it. PATIENTS AND METHODS: In 29 patients thrombin was injected
      directly into the false aneurysm of the femoral artery, caused by catheter
      introduction into the vessel. Puncture of the aneurysm and injection of the
      thrombin solution was performed with continuous duplex-sonographic monitoring.
      The patients' age ranged from 42 to 88 years (mean 71 +/- 12 years). The false
      aneurysm had occurred after diagnostic catheterization (n = 5), balloon
      dilatation of peripheral vessels (n = 5) or balloon catheter dilatation of the
      coronary arteries (n = 19) with catheters size 5 F (n = 4), 6 F (n = 6), 8 F (n =
      16) or 9-13 F (n = 3). The catheterization had been done 1-30 days previously
      (mean 5.3 +/- 6.9 days). The diameter of the aneurysm ranged from 2.1 to 5 cm
      (mean 3.5 +/- 0.9 cm). RESULTS: The aneurysms thrombosed within seconds after
      injection of 0.075 to 1.5 ml (mean 0.4 +/- 0.4 ml). All interventions were
      successful and without complications. Any resulting haematoma regressed within a
      few days to a few weeks and none recurred. In two patients a persisting haematoma
      had later to be removed surgically, and in another patient a second aneurysm was
      removed surgically without prior thrombin injection. CONCLUSION: A false aneurysm
      of the femoral artery caused by percutaneous catheterization can be successfully
      thrombosed by direct thrombin injection.

PMID- 10929538
TI  - [Pseudostenocardia due to exposure to "electrosmog"].
AB  - HISTORY AND REASON FOR ADMISSION: A 44-year-old man had anginal-like complaints.
      He was convinced that cardiac problems had been caused by electromagnetic fields.
      INVESTIGATIONS: Apart from hypertension and hyperlipidaemia there were no other
      significant findings. ECG, ergometry Holter-ECG were normal. EXPERIMENT: We tried
      to verify with a double-blind provocation test if the patient's complaints had
      been caused by electromagnetic fields. The patient was exposed to an electric
      instrument without being aware whether it was switched on or off. He was
      questioned about his perception of the presence of an electric current.
      CONCLUSION: The results of the test showed that there was no causal relation
      between the patient's angina-like-symptoms and electromagnetic fields. The
      phenomenon of electrosensitivity was probably caused by psychological mechanisms.

PMID- 10929537
TI  - [The stiff-man syndrome with diabetes mellitus type 1 and autoimmune
      thyroiditis].
AB  - HISTORY AND ADMISSION FINDINGS: A 54-year-old woman with type 1 diabetes of about
      2 years' duration developed painful cramps in the muscles of the abdominal wall,
      the back and the thighs. On admission physical examination confirmed markedly
      increased tone of the muscles of the trunk and those proximal to it.
      INVESTIGATIONS: Markedly increased amounts of anti-GAD (glutamic acid
      decarboxylase) antibodies were present in both serum and cerebrospinal fluid
      (CSF). Electroneurography and -myography revealed mild polyneuropathy but no
      other neurological abnormality. DIAGNOSIS, TREATMENT AND COURSE: Suspected stiff
      man syndrome (SMS) was confirmed by the increased anti-GAD antibodies and the
      marked improvement on gradually increasing doses of clonazepam. The autoimmune
      syndrome affected several organ systems: central nervous system (SMS), pancreas
      (diabetes), thyroid (immuno-thyroiditis). Immunosuppressive treatment with
      azathioprine was begun. The patient remains in good general condition 22 months
      after the initial diagnosis, and there have been no new organ involvement.
      CONCLUSION: It is important to include SMS in the differential diagnosis, even
      though the symptoms are not those of the full-blown picture of this rare disease.
      Absence of muscle cramps and myoclonus but presence of depressive symptoms can
      easily result in misdiagnosis, preventing early initiation of effective
      symptomatic treatment.

PMID- 10929539
TI  - [The pharmacotherapy of the cognitive disorders in Alzheimer's disease.
      Guidelines for rational drug use--a review].

PMID- 10929540
TI  - [The detection of tumor cells in the bone marrow, peripheral blood and
      leukapheresis products in breast carcinoma patients].

PMID- 10929541
TI  - [The precedence of the admissibility of the hospital for ambulatory surgery over
      the authority of the chief physician? The judgement of the Federal Social Court
      of 9 June 1999].

PMID- 10929542
TI  - [The history of organ transplantation in the mirror of the DMW].

PMID- 10929543
TI  - [Stillbirth in APC resistance and ulcerative colitis].

PMID- 10929545
TI  - Extramural grant program 1999. Chicago, Illinois, USA. May 17-18, 1999.
      Abstracts.

PMID- 10929544
TI  - [Interdisciplinary centers for clinical research. Biomaterials: the focal point
      in Aachen].

PMID- 10929546
TI  - 5th Meeting of the European Society of Neurosonology and Cerebral Hemodynamics.
      Graz, Austria, May 21-23, 2000. Abstracts.

PMID- 10929547
TI  - 10th Meeting of the European Neurological Society. Jerusalem, Israel, 18-22 June
      2000. Abstracts.

PMID- 10929548
TI  - The Physiological Society proceedings of the scientific meeting held at Imperial
      College, London, United Kingdom. 12-14 April 2000.

PMID- 10929550
TI  - World Congress on Osteoporosis 2000. Chicago, Illinois, USA. June 15-18, 2000.
      Abstracts.

PMID- 10929549
TI  - 7th International Conference on Alzheimer's Disease and Related Disorders.
      Washington, DC, USA. July 9-18, 2000. Abstracts.

PMID- 10929551
TI  - [Aspects of quality assurance in plastic surgery. Subjective well-being and
      satisfaction of 420 plastic surgery patients with preoperative counseling,
      surgical intervention and after-care].
AB  - The aim of quality assurance should be the improvement of medical treatment.
      Beside quality assurance measures, which are mainly based on clinical parameters
      and medical ratings, subjective opinions of patients gain more and more in
      importance. In the present study results of an inquiry of 420 plastic-surgical
      patients with preoperative consultation, plastic surgery, and postoperative
      consultation are shown. The priority weakness on the wards was a high
      dissatisfaction of the patients with the lounges, the sanitary facilities,
      equipment and size of the rooms. Information about treatment after discharge was
      often not quickly and completely passed on, besides, there was in many cases a
      delay in the recommended physiotherapy after discharge. As a consequence of this
      study, improvements based on the results shown are required.

PMID- 10929552
TI  - [Quality assurance in plastic surgery--initial experiences with "breast
      reduction" tracer diagnosis].
AB  - Quality assurance has to be an integral part of medical work as it is required by
      actual health laws. "Tracers" have been used in different parts of medicine as a
      reliable method. In 1997 we started to establish an internal program for a
      quality assurance with five different tracers (breast augmentation, breast
      reduction, oncological and reconstructive breast surgery, liposuction). The
      outcome is prospectively documented using an operation-specific documentation
      form. Every three months, the results are discussed in a surgical audit. The
      overall complication rate after mamma reduction (n = 81) was reduced about 40% to
      21% (mean reduction weight 1.7 kg). Therefore, these measurements could promptly
      improve the quality of treatment of our patients.

PMID- 10929553
TI  - [A comparison of long-term outcome of 6 techniques of breast reduction].
AB  - In a retrospective study we examined 192 patients who underwent breast reduction
      between 1973 and 1993 to compare the long-term results of six various reduction
      mammaplasty techniques. We investigated patient's satisfaction, the relief of
      preoperative symptoms as well as the possibility of lactation. The sensitivity of
      the areola was measured with Semmes-Weinstein monofilaments and the breast
      contour, the scar formation, and the complication rate were evaluated. 89% of our
      patients were very satisfied with the cosmetic result. Breast-feeding was
      possible after all techniques except for free-nipple grafting. The sensitivity of
      the areola was found to be more decreased after using a superior pedicle
      technique. Breast ptosis was obtained in 30% of our patients and correlated
      significantly with postoperative weight loss. Breast ptosis was less frequent
      after using an inferior pedicle technique. Length and width of the scar, as well
      as the complication rate correlated with the resection weight.

PMID- 10929554
TI  - [Color comparison of donor sites of free flaps and the face].
AB  - Microsurgical reconstructions of the face using free flaps from the body and the
      extremities often lead to imperfect aesthetic results. In order to find the
      optimal free-flap donor site with respect to its colour we compared the colour of
      the face and of typical free-flap donor sites. In a study of 19 healthy, untanned
      subjects with skin type II-III (Fitzpatrick 1988), we measured the colour of four
      facial areas and of ten common free-flap donor sites and compared them
      statistically. Measurements were carried out with a Minolta CR-300 chromameter
      and the CIELAB colour system. We found that the face itself can be divided into
      two statistically significant different colour regions. The forehead-, cheek- and
      mandible areas have a distinctly different colour than the nose. The donor sites
      showing the best colour match with the forehead-, cheek- and mandible area were
      pectoralis, lateral upper arm, radialis, fibula, and latissimus. The nose area is
      clearly darker and less colourful. For this reason the colour match of all the
      free-flap donor sites in our investigation is poorer. Here the best suited donor
      site area is still the dorsalis pedis area.

PMID- 10929555
TI  - [Expanded pedicled forearm flap for reconstruction of multiple finger
      amputations].
AB  - Soft-tissue injuries of the hand frequently require flap coverage to preserve
      structures damaged at the time of injury or to facilitate later reconstruction.
      The radial forearm flap makes local tissue readily available and offers a simple
      method of reconstruction. Secondary augmentation of the skin flap by means of
      tissue expansion appears to be a useful alternative to improve the possibilities
      of reconstruction. This case report describes a primary reconstruction of a hand
      with multiple finger amputations using both techniques: Forearm flap and tissue
      expansion.

PMID- 10929556
TI  - [Treatment and outcome of complications after free flap-plasty].
AB  - Free tissue transplantation is a routine procedure in reconstructive surgery.
      Although a lot of free flap techniques have been described, the postoperative
      management of complications has gained only little interest. Nevertheless,
      complications of perfusion after free tissue transplantation are not rare and
      require a systematic approach. The aim of this study is to classify perfusion
      failures with a simple grading system prospectively on a large clinical series
      and to evaluate the results of treatment to improve management. In the past ten
      months, 70 consecutive free flaps have been performed. By the end of the
      operation, the operating surgeon gave a prognosis concerning the probability of a
      possible perfusion complication. Postoperative monitoring was done exclusively by
      clinical examination (colour, time for recapillarisation and bleeding after
      puncture). According to these parameters, arterial and venous insufficiencies
      have been classified into four grades. After recording type, time and treatment
      of a postoperative complication, the result of treatment was rated subjectively
      and a cause was noted when possible. The final result was classified either as
      total flap loss, partial flap loss or successful tissue transplantation. A total
      of 28 (40%) complications, which were treated with an average of 2.1 options,
      were recorded. The ratio between arterial and venous failure was 15:13. In 21
      cases surgical intervention became necessary (intraoperative n = 12,
      postoperative n = 9). The arising complication was diagnosed correctly in nine
      cases by the operating surgeon. In ten cases, the cause of the complication
      remained unclear. In 18 cases, the complication was treated successfully without
      any flap loss. In six cases partial flap loss was observed and in four cases a
      total flap loss had to be accepted. Our results confirm that only few objective
      criteria for treatment options with perfusion failures after free tissue
      transplantation exist. Nevertheless, the presented classification is a useful
      tool for standardized evaluation of the results. The various salvage techniques
      result in positive outcomes for most of the patients.

PMID- 10929557
TI  - [Cultivating human Schwann cells for tissue engineering of peripheral nerves].
AB  - Cultivation of human cells is well established. The cultivation of human Schwann
      cells may offer a new therapeutic approach for treatment of degenerative and
      traumatic lesions of the peripheral nervous system. Currently, Schwann cells in
      combination with other biological matrices are used as tissue-engineered
      biological nerve grafts in animal models. Cultivation of human Schwann cells,
      however, is more difficult than cultivation of rodent cells. A high cell yield is
      only achieved by pharmacological stimulation, which should not be used in
      clinical therapy. Thus, we aimed to establish an easy method of cultivating human
      Schwann cells from peripheral nerve neuromas that have developed after a complete
      nerve lesion. As these neuromas have to be resected in any case to allow proper
      nerve reconstruction, their removal does not lead to additional neurological
      defects. Schwann cells were cultivated from the neuromas of eleven patients, aged
      5 to 75 years. All patients suffered from a complete median nerve lesion at the
      level of the distal forearm, which could not be treated primarily. Two weeks
      after trauma, the patients underwent secondary reconstruction by autologous sural
      nerve grafts. During this operation, the neuromas were resected. Control cultures
      were established from remaining parts of the sural nerve. Cell yield was
      determined on the first, third and seventh day in vitro. Schwann cells were
      stained for S100. Viability was assessed with fluoresceine-fluorescence. The cell
      count was assessed with regard to the donor age. The growth rate of Schwann cells
      was found to be donor-age dependent. The highest cell yield was obtained from
      adult neuromas. By the third day in vitro, they showed a 1.5 fold increased cell
      count compared with juvenile nerves and neuromas. By the seventh day in vitro,
      Schwann cells from adult neuromas were increased 2.5 times compared with cells
      from juvenile nerves and 7 times compared to cells from adult sural nerves.
      Cultivation of Schwann cells taken from sural nerves of patients older than 65
      years was not possible. The utilization of neuromas as a source for human Schwann
      cells allows an age-independent cultivation within a short time period without
      any pharmacological treatment. These neuromas are virtually predegenerated and
      show an activation of Schwann cells implying good adherence and high mitotic
      activity in culture. Normal nerve tissue as a source for Schwann cells for tissue
      engineered nerves is only sufficient in young patients due to its greater
      proliferative potential. The age-dependent proliferation underlines the need for
      alternative sources for Schwann cells.

PMID- 10929558
TI  - [Improving microcirculation of muscle flaps by tissue plasminogen activator in
      the rat cremaster muscle flap model].
AB  - Currently, tissue-plasminogen activator (t-PA) is the most potent and
      nevertheless safe fibrinolytic in clinical use. Its indications are fibrinolysis
      in acute myocardial infarction, ischemic stroke, deep vein thrombosis, pulmonary
      thromboembolism, as well as different kinds of peripheral arterial embolism.
      However, controlled studies on the effect of t-PA in microsurgery and free tissue
      transplantation are lacking. This study was designed to evaluate the effect of
      tissue-plasminogen activator on skeletal muscle flap perfusion after a
      thrombogenic stimulus. 24 male Sprague-Dawley rats were divided into four
      experimental groups of six animals each. In group 1, the cremaster was isolated
      as an end organ flap, in group 2 after cremaster isolation a semicircular
      inverted suture as a thrombogenic insult was performed at the ipsilateral common
      iliac artery. In group 3, local t-PA infusion followed the inverted suture and in
      group 4, vehicle was infused. After 24 hours, we measured cremaster muscle flap
      hemodynamics using intravital microscopy. Capillary perfusion significantly
      decreased after the inverted suture from 6.23 (group 1) to 1.50 (group 2)
      functional capillaries per visual field (medians). t-PA significantly increased
      capillary perfusion after the thrombogenic insult from 1.50 (group 2) and 2.50
      (group 4) to 6.00 (group 3) (medians). Restoring capillary perfusion after a
      thrombogenic insult t-PA may increase flap survival rates.

PMID- 10929559
TI  - [Does tissue perfusion after free microvascular tissue transplantation remain
      autonomous?].
AB  - In a retrospective study, including 60 patients, after free latissimus dorsi
      transplantation (FLDT) to the lower leg, we found persistent pedicle blood flow
      up to ten years postoperatively. After uncomplicated FLDT, the pedicle supported
      the flap in all cases. After complicated FLDT (hematoma, thrombosis, infection)
      only 50% of all flaps after ten years were perfused by the vascular pedicle.

PMID- 10929561
TI  - [The current role of endoscopy within the scope of the German Speaking Study
      Group of Microsurgery of Peripheral Nerves and Blood Vessels--results of a
      survey].
AB  - PURPOSE: The present survey among the members of the DAM deals with the
      application of endoscopic methods in plastic and reconstructive procedures.
      Special interest is focussed upon endoscopically assisted microsurgery. METHODS:
      A questionnaire was sent to all members of the DAM. It contained questions about
      the application of endoscopic techniques, the types of operations performed with
      the endoscope, the advantages, disadvantages, and complications of endoscopic
      operations. RESULTS: In 26 of 40 cases the question about the application of
      endoscopic techniques was answered positively. The most frequent indications were
      carpal tunnel release, wrist arthroscopy, the harvesting of flaps, breast
      reconstruction, and implantation of expanders. Incomplete release of the flexor
      retinaculum and partial lesions of the median nerve in patients referred from
      other departments were listed as complications. CONCLUSION: Endoscopic techniques
      have found acceptance among the DAM-members, but are restricted to traditional
      indications such as arthroscopy, carpal tunnel release, and aesthetic procedures.
      Future attempts must attract the interest of industrial companies for the
      development of high-resolution endoscopes for microsurgery.

PMID- 10929560
TI  - [Axillary plexus catheter block in accidental intra-arterial levomethadone HCl
      injection in an HIV-positive, hepatitis B and C active drug dependent patient].
AB  - We report the case of a 36-year-old male patient who inadvertently injected
      intraarterially (radial artery) levomethadon-HCl-solution (15 ml corresponding to
      37.5 mg) which was intended for substitutional use only. He subsequently
      developed all clinical signs of malperfusion of his left lower arm and entire
      hand. Reaching the clinic only two hours after the injection, he received a
      continuous axillary plexus block which led to the nearly complete restoration of
      the perfusion of his left lower arm and hand. Thus, we were able to avoid further
      surgical interventions. We were using the new local anesthetic substance
      Ropivacain (Naropin), which offers the advantage of 12-hour-injection intervals.
      Already 36 hours after the "trauma", colour-coded Doppler sonography demonstrated
      normal flow-rates of the radial, ulnar, and common digital arteries. Only the
      arterial flow of the index and middle fingers was not detectable at that time-
      corresponding to partial hypaesthesia of the tip of the second and radial side of
      the third digits. Even if there are no studies concerning the continuous axillary
      plexus block in HIV, hepatitis B- and C-positive patients, this
      anaesthesiological technique should not be withheld from this group of
      immunocompromised patients.

PMID- 10929562
TI  - [Guidelines of the German Society of Hand Surgery].

PMID- 10929563
TI  - Why I continue to support community water fluoridation.

PMID- 10929564
TI  - Response and nonresponse bias in oral health surveys.
AB  - Oral health surveys are undertaken to provide estimates of the dental health and
      behaviors of populations or population subgroups. However, the integrity of the
      data from sample surveys may be compromised by one or more sources of sampling
      and nonsampling error. An important source of nonsampling error is the failure to
      collect data from some of the individuals comprising the sample. Consequently,
      the response to a sample survey, and the direction and magnitude of bias induced
      by nonresponse, need to be taken into account when using estimates derived from
      sample surveys. Although the response rate to a survey is usually used as an
      indicator of the quality of the data it provides, nonresponse error is a function
      of nonresponse and the extent of differences in the characteristics of responders
      and nonresponders. Nonresponse may be managed in two ways. The first is to reduce
      nonresponse to a minimum using response-enhancement strategies. The second is the
      post-survey adjustment of data using weighting or imputation techniques to
      produce estimates that correct for nonresponse. This paper discusses issues
      concerning response and nonresponse bias in oral health surveys and provides
      guidelines on the management and reporting of nonresponse. It describes response
      enhancement strategies to reduce noncontacts and refusals, sources of data to
      facilitate the comparison of responders and nonresponders, methods of assessing
      the degree of bias induced by nonresponse, techniques for producing adjusted
      survey estimates, and the assumptions on which these procedures and processes are
      based.

PMID- 10929565
TI  - Identification of adult populations at high risk for dental caries using a
      computerized database and patient records: a pilot project.
AB  - OBJECTIVES: The purpose of this study is to test the usefulness of dental
      insurance claims history, supplemented with radiographic caries diagnoses, as a
      means of identifying caries-active and caries-inactive working adults, as
      determined by bacterial levels. Computerized identification of at-risk groups may
      facilitate subject selection for clinical trials designed to test caries
      preventive strategies. METHODS: Two groups of subjects were initially selected
      from an insurance database based upon their dental service utilization during a
      one-year period: a "low restorative" group of individuals defined as persons who
      had received no restorative treatment, and a "high restorative" group comprised
      of individuals who had received at least three multisurfaced restorations. A
      chart review confirmed a diagnosis of caries in the high restorative group and an
      absence of caries in the low restorative group. Subjects were then approached for
      saliva collection. The low and high restorative groups were compared for salivary
      mutans streptococci and lactobacilli levels, stimulated flow rate, and buffer
      capacity (n = 48). RESULTS: The high and low restorative groups differed in
      mutans streptococci levels, but not on other measures. CONCLUSIONS: A group of
      subjects who had recently received multisurfaced restorations that were placed
      for reasons of caries had significantly higher levels of mutans streptococci and
      potential for continued caries activity when compared to a group of subjects who
      had received no restorations and were caries free.

PMID- 10929566
TI  - President's Award: Teresa A. Dolan, DDS, MPH.

PMID- 10929567
TI  - 1999 Special Merit Award: Jane A. Weintraub, DDS, MPH.

PMID- 10929568
TI  - 1999 International Special Merit Award for Community Dentistry: Mario M. Chaves,
      DDS, MPH.

PMID- 10929569
TI  - 1999 Distinguished Service Award: Alice Horowitz, PhD.

PMID- 10929570
TI  - Communicating with new sex partners: college women and questions that make a
      difference.
AB  - Despite efforts of sexuality educators, many college women are uninfluenced by
      information about risks of contracting a sexually transmitted disease or
      initiating an unintentional pregnancy. This study used an anonymous questionnaire
      administered to 438 never-married undergraduate women to investigate the failure
      of college women to ask new sex partners about sexual histories prior to sexual
      intercourse. Significant differences were found between the three subsample
      groups: those who "almost always" (AA), "sometimes" (S), or "rarely" (R) asked
      their sex partners about sexual histories. At first sexual intercourse, AA group
      women were significantly more likely to have been in a committed relationship, to
      have been contracepted, and to have been older; and they were less likely to have
      been under the influence of alcohol or other mind-altering substances.
      Furthermore, AA group women also reported fewer sex partners than other
      respondents. They also were more likely to discuss sexually related topics with
      their partners, to reach sexual decisions by their own thoughts, and to set
      personal goals.

PMID- 10929571
TI  - Effect of bupropion-SR on orgasmic dysfunction in nondepressed subjects: a pilot
      study.
AB  - The objective of this study was to determine whether the aminoketone
      antidepressant bupropion has beneficial effects in orgasmic dysfunction. DESIGN:
      Single-blind, sequential treatment order of three weeks each: placebo, bupropion
      SR 150 mg/day, bupropion-SR 300 mg/day. SUBJECTS: Nondepressed women (n = 20) and
      men (n = 10) having nonphysiologic orgasmic delay or inhibition. MAIN OUTCOME
      MEASURES: Reported difficulty or delay in achieving orgasm, satisfaction with
      orgasm and erectile function, and subjective impressions of drug effect. RESULTS:
      In the women, there were significant improvements relative to baseline (p < .01)
      on both doses of bupropion-SR in all measured aspects of sexual function, and
      significant improvements relative to placebo (p < .05) in overall sexual
      satisfaction on both doses and satisfaction with intensity of orgasm on 150
      mg/day (300 mg/day, p = .10). In the men, significant improvements over baseline
      (p < .01) were observed with both doses in overall sexual satisfaction, ability
      to achieve an erection, and delay in reaching orgasm/ejaculation; significant
      improvements relative to placebo (p < .05) were observed in overall sexual
      satisfaction on both doses, ability to achieve erection on 150 mg/day, and delay
      in orgasm/ejaculation on 150 mg/day. Seventy percent of subjects reported
      improvement in libido, arousal, or orgasmic function during bupropion
      administration. CONCLUSIONS: Bupropion-SR may be a useful agent for treating
      orgasmic delay and inhibition, and possibly disorders of sexual arousal. The
      results argue against bupropion's apparent prosexual effect in depressed patients
      being simply a result of its antidepressant activity.

PMID- 10929572
TI  - Sexual life after breast cancer.
AB  - The trauma of being diagnosed and treated for breast cancer can impact greatly on
      womens' psychosexual functioning and intimate relationships. Survivors of breast
      cancer report that issues of body image, sexuality and partner communication
      rarely are addressed by traditional health care providers (Ganz, Rowland,
      Desmond, Meyerowitz, & Wyatt, 1998). Psychotherapy can help women cope with
      difficult changes in body image and sexual functioning, and there is evidence
      that psychotherapy may prolong life (Speigel, Bloom, Kraemer, & Gottheil, 1989).
      However, many mental health professionals are not comfortable addressing sexual
      issues, nor are they well versed in the medical aspects of the disease and its
      treatment. It would seem that marital and sex therapists are better equipped than
      most to provide mental health services to breast cancer patients.

PMID- 10929573
TI  - Sexuality training for psychiatry residents: a national survey of training
      directors.
AB  - The current status of training in human sexuality is relevant to all health care
      professionals. The purpose of the current study was to determine the extent of
      sexuality training offered in psychiatric residency programs. The training
      directors of psychiatry residencies were surveyed with regard to the number of
      expert faculty in sexuality training as well as resident exposure to seven
      related curricular areas. Of the 69 respondents, the majority reported expert
      faculty in sexual dysfunctions, sex therapy, therapy with gay/lesbian patients,
      and HIV/AIDS. For each sexuality topic, approximately 80% of programs reported
      curricula offerings through either didactics or clinical rotations. For
      didactics, most topics were presented in the context of a broader course. With
      the exception of HIV/AIDS, it was rare for programs to offer a clinical rotation
      involving sexuality issues. In conclusion, the majority of training programs in
      psychiatry provide curriculum offerings in sexuality training, primarily through
      didactic education. Results are discussed with regard to comparison to training
      in professional psychology and the need for assessment of sexuality training in
      health care professions generally.

PMID- 10929574
TI  - The coital alignment technique (CAT): an overview of studies.
AB  - The Coital Alignment Technique (CAT), a basic physiological alignment that
      provides consistent and effective stimulation for female coital orgasm, has been
      evaluated in a series of controlled studies. An overview of the CAT is discussed
      as well as related studies including replication studies, and subsequent studies
      of Orgasm Consistency Training (OCT), which incorporates the CAT technique.
      Classic sex problems like female coital anorgasmia and premature ejaculation and
      modern day epidemic-level sex problems such as hypoactive sexual desire are
      analyzed in relation to a syndrome of sexual dysfunction symptoms devolving from
      failed intercourse. Studies indicate that some symptoms of sexual dysfunction
      considered to have their etiological foundations in pathology are the result of
      ineffective intercourse techniques.

PMID- 10929575
TI  - Controlled studies on women presenting with sexual drive disorder: I. Endocrine
      status.
AB  - A single mid-cycle blood sample was obtained from 15 premenopausal female
      patients presenting with lifelong absence of sexual drive and from a control
      group of women with intact sexual drive. Serum levels of testosterone, 5
      dihydrotestosterone (5-DHT), 17 beta oestradiol, sex hormone binding globulin,
      and prolactin were measured and indices of free testosterone and 5-DHT were
      derived. During the menstrual cycle in which the blood samples were obtained, the
      study subjects kept a diary of their sexual desire and activities. The only
      endocrine parameter that is significantly different between the two groups is
      free testosterone, which is lower in the patients than in the control women.
      Associations between endocrine parameters and indices of sexual behavior were
      examined. In the control group, average daily sexual thoughts correlates
      positively with total testosterone, free testosterone index, and free 5-DHT.
      Feeling of "need for sex" correlates positively with free 5-DHT index and free
      testosterone index. Experience of sexual thoughts correlates with need for sex,
      and average frequency of masturbation correlates negatively with age. In both
      groups, average coital frequency correlates with free testosterone index.

PMID- 10929576
TI  - Heritage of the cradle of civilization--exit from the Garden of Eden.

PMID- 10929577
TI  - The contributions of Arabs to medicine. 1984.

PMID- 10929578
TI  - Arab medicine and society. 1974.

PMID- 10929579
TI  - Anesthesia 1000 years ago. 1991.

PMID- 10929580
TI  - Perspectives of the history of anesthesia. 1997.

PMID- 10929581
TI  - Middle eastern history of anesthesia. 1997.

PMID- 10929582
TI  - Anesthesia in Arab and Islamic medicine. 1978.

PMID- 10929583
TI  - Historical aspects of opium. 1982.

PMID- 10929584
TI  - Discovery of the pulmonary circulation by an Arab in the thirteenth century.
      1968.

PMID- 10929585
TI  - The larynx in Islamic medicine. 1981.

PMID- 10929586
TI  - The origin of the "algorithm". 1998.

PMID- 10929588
TI  - Radioimmunotherapy effective first-line treatment for non-Hodgkin's lymphoma.

PMID- 10929587
TI  - Permanent prostate brachytherapy: lessons learned, lessons to learn.
AB  - Current techniques for permanent prostate brachytherapy are associated with
      excellent biochemical control in patients with localized prostate cancer. Data
      now available confirm 5- to 10-year results with this treatment modality that are
      comparable to those with external-beam irradiation or radical prostatectomy.
      Nonetheless, treatment protocols and techniques for prostate brachytherapy vary
      from center to center. Controversy exists regarding the selection of patients for
      brachytherapy alone or in combination with external-beam irradiation. The role of
      neoadjuvant androgen deprivation also remains undefined in patients with
      localized prostate cancer. Matched-pair analysis studies performed at Memorial
      Sloan-Kettering Cancer Center have examined the role of isotope selection, the
      addition of external-beam irradiation, and the use of neoadjuvant androgen
      deprivation. These studies provide insights into the use of permanent
      brachytherapy in patients with localized prostate cancer. In addition,
      postimplant dosimetry needs to be a requirement for centers performing seed
      implants. Data now appear to support specific computed tomography-based criteria
      to evaluate implant quality and delivered dose to the prostate. Unfortunately,
      prostate edema and poor imaging techniques limit the evaluation of implant
      dosimetry. Treatment planning techniques that utilize new imaging modalities,
      coupled with computerized treatment planning, may help improve the implant
      procedure and dosimetry.

PMID- 10929589
TI  - Current surgical management of metastatic spinal disease.
AB  - Despite advances in the treatment of many malignancies, a large number of cancer
      patients will require evaluation and possible surgical intervention for lesions
      that have metastasized or directly invaded the spinal column. The need for
      heightened awareness of and aggressive early intervention for spinal metastases
      is underscored by many studies that have reported a relationship between
      pretreatment and posttreatment neurologic function in these patients.
      Recommendations for operative intervention should be made following an evaluation
      of the patient by multiple specialties, both medical and surgical. In the last
      decade, advances in surgical techniques for tumor decompression and spine
      stabilization, neurophysiologic monitoring, and anesthetic expertise have allowed
      surgeons to perform more extensive procedures with improved outcomes and reduced
      morbidity. This article will review the factors favoring an operative
      recommendation in patients with metastatic spinal disease, preoperative
      evaluation, and available surgical options. Patients with symptomatic spinal
      metastases should receive early surgical consultation as part of a
      multidisciplinary approach to their disease process.

PMID- 10929590
TI  - Clinical trials referral resource. Current clinical trials in cervical cancer.

PMID- 10929591
TI  - Cutaneous T-cell lymphoma: pathogenesis and treatment.
AB  - Cutaneous T-cell lymphoma (CTCL) is a malignancy of a distinctive subset of T
      helper cells designated "cutaneous T cells" because of their central role in the
      normal functioning of the skin immune system. Guided by selective adhesion
      molecules, activated/memory T cells of the skin immune system normally circulate
      among the skin, lymph nodes, and peripheral blood. Thus, a better understanding
      of the skin immune system, which normally functions to provide immunosurveillance
      against cutaneous pathogens and other insults, has led to a better understanding
      of the clinical spectrum, pathogenesis, staging, and management of CTCL. This
      article describes the major subtypes of CTCL and provides an update on the
      pathogenesis and treatment of this lymphoma.

PMID- 10929592
TI  - Management of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is responsible for a significant amount of
      morbidity and mortality throughout the world. In many countries, including the
      United States, a definite increase in the incidence of HCC has been reported
      recently, largely attributable to the increasing incidence of hepatitis C
      infection. Unfortunately, the current management of HCC is confusing due to the
      large number of treatment options available. The difficulty of managing a patient
      with HCC is compounded by the lack of well-designed, randomized clinical trials
      comparing the various treatment modalities. Nevertheless, many exciting
      management options are currently available that may prove valuable in the
      treatment of this disease. Partial hepatic resection or, in some instances, liver
      transplantation offers the best chance for cure. However, various ablative
      therapies, including percutaneous ethanol injection, radiofrequency ablation, and
      cryosurgery, may produce a survival benefit. In the future, systemic chemotherapy
      and transarterial chemoembolization, employed either alone or as adjuncts to
      ablation or resection, may play an increasing role in palliating or down-staging
      a patient with advanced HCC. This overview of the state-of-the-art management of
      HCC attempts to guide the practicing physician in selecting the best treatment
      plan for an individual with HCC.

PMID- 10929593
TI  - [Mammography or mammary ultrasonography?].

PMID- 10929594
TI  - [Does ultrasonographic-morphologic staging of lymph nodes in head and neck cancer
      lend itself to automation?].
AB  - OBJECTIVES: B-scan ultrasound imaging is an obligatory examination of great
      clinical relevance in patients with head and neck cancer. The procedure, however,
      is dependent on an experienced examiner and thus requires higher personal
      resources than other examination techniques. In addition, its subjective
      character leads to possible deficits in reliability and objectivity. Established
      sonomorphologic criteria (echo-contour, echo-density, echo-structure, boundary)
      should therefore be matched to the findings of computer aided sonomorphometry.
      METHOD: 200 sonographic images of the cervical region of patients with oral
      carcinoma were analysed semi- and fully automatically as well as interactively by
      standard image analysis software (Quantimed 500, Leica, Germany). The results
      were evaluated statistically and correlated to the findings of both an
      experienced and inexperienced examiner. RESULTS: Fully automatic image analysis
      was impossible, as the software did not correctly identify the lymph nodes
      without interactive support. Quality of the semiautomatic and interactive image
      analysis mainly depended on the correct manual identification of the boundaries
      of the lymph node. Regarding this criterion the image analysis software was not
      able to compensate for the deficits of an inexperienced examiner. CONCLUSION:
      Delegation of the sonographic analysis to inexperienced, less qualified
      personnel, even with the help of image analysis software, seems to be
      inadvisable. This is especially the case if three-dimensional information from
      the real time analysis is not available.

PMID- 10929595
TI  - [Sonographic representation of the normal and acute inflamed appendix--in
      patients wi right-sided abdominal pain].
AB  - The detectability, vascularization and size of the normal and inflamed appendix
      were investigated in the study. 148 patients under suspicion of appendicitis or
      with lower right abdominal pain were studied over a period of five months
      beginning in January 1998. An ultrasound-transducer was employed at a wave length
      of 3.5 MHz to 10 MHz. Vascularization was measured using 'Duplex' and 'Color
      Angio'. The results were compared with operative evidence, histology and patient
      history. The appendix was detected in about 30% of the cases (47/148). But of the
      presumably normal appendices only 12% (13/109) were detected. 27 appendices
      sonographically diagnosed as acutely inflamed were confirmed by operation and
      phlegmonic. The acute appendicitis was sonographically diagnosed with a
      sensitivity of 82% and a specificity of 95%. The diameter of the normal
      appendices was an average of 5.5 mm, that of the acute was 12.2 mm whereby 21 of
      25 organs were at least 9 mm. The measurement of the organ size seems to be more
      helpful than the detection of vascularization. Both methods alone cannot detect
      the acute phlegmonic appendicitis. The normal appendix was less frequently
      detected than described in current literature. Patients with pain present
      difficulties in ultra-sound examination because both the cooperation and the time
      for the correct diagnosis are limited.

PMID- 10929596
TI  - [Improving the visibility of intracranial vessels with the echo-enhancing
      substance Levovist in duplex sonography].
AB  - AIM: To evaluate the diagnostic advantages of Levovist for contrast enhancement
      of intracranial arteries in a routine clinical setting. METHOD: Routine
      cerebrovascular extracranial Doppler- and duplex-sonography was performed in 3990
      patients (1791 female, 2189 male, mean age 50.4 years). In addition 879 trans
      temporal, 990 trans-foraminal and 99 trans-orbital trans-cranial colour-coded
      duplex investigations were performed on these patients. Signal quality was
      classified in the categories: 'no signal', 'insufficient signal' and 'sufficient
      signal'. Patients classified as having 'no' or 'insufficient' signal quality
      underwent an additional examination after application of Levovist. RESULTS: 879
      patients underwent trans-temporal examination. In 89 (9.1%) of these patients
      signal quality in the trans-temporal examination proved to be insufficient, thus
      indicating the use of Levovist. 346 of the examined vessels (72%) were originally
      classified as showing 'no signal'; this number could be reduced to 82 (23.9%)
      after applying Levovist. Of the 99 arteries (21%) falling into the category
      'insufficient signal', only 4 (4%) did not show signal improvement after
      application of Levovist. 990 patients were examined by the trans-foraminal
      approach, and Levovist was given to just 26 patients (2.6%). Without enhancement,
      20 basilar arteries (77%) showed 'no' or 'insufficient' signal, whereas after
      injecting Levovist only 4 (13.25%) remained in these categories. Of 13 vertebral
      arteries (25%) with 'no' or 'insufficient' signal intensity, 3 (5.8%) showed no
      improvement in imaging quality after application of Levovist. CONCLUSION: Imaging
      problems of intracranial arteries are dramatically reduced by Levovist.

PMID- 10929597
TI  - [Lethal osteochondrodysplasias: prenatal and postnatal differential diagnosis].
AB  - PURPOSE: Lethal osteochondrodysplasias show an abnormal maturation and a
      disturbed growth of cartilage and bones. They represent a heterogeneous group of
      rare genetic diseases. Their incidence is 1 to 3 in 10,000 births. MATERIAL AND
      METHODS: We report altogether 5 cases: two of thanatophoric dysplasia, one of
      achondrogenesis type II and two cases of the rare fibrochondrogenesis. The
      differential diagnosis in respect to ultrasonographic, morphologic, radiographic
      and histopathologic criteria of the most common of these diseases are discussed
      together with a review of the literature. RESULTS: On the basis of the ultrasound
      finding of the short-rib-syndrome, it is possible to differentiate between viable
      and lethal osteochondrodysplasias at 19 to 22 weeks of gestation. The short-rin
      syndrome leads to pulmonary hypoplasia. CONCLUSIONS: It is essential to obtain an
      exact diagnosis postnatally by radiographic and histopathological examinations to
      counsel the parents concerning the risk of recurrency. The risk in this
      heterogeneous group of genetic diseases ranges between less than 1% up to 50%
      depending on the final diagnosis. Our two cases of fibrochondrogenesis in a
      consanguineous couple strongly suggest an autosomal recessive inheritance in this
      disease.

PMID- 10929598
TI  - [Sonographic changes after total hip joint replacement].
AB  - The value of ultrasonographic imaging after total hip arthroplasty (THA) has not
      been described in the literature so far. AIM: The typical postoperative
      sonographical findings are to be presented thus creating a basis for detecting
      pathological alterations. METHOD: 73 consecutive patients after THA were
      sonographically and clinically examined at the beginning and the end of the
      clinical rehabilitation phase. Laboratory tests detecting signs of inflammation
      and coagulation disorders were also performed. RESULTS: In the early
      postoperative phase collection of liquid and its delayed resorption are the most
      important findings. The haematoma of the joint is usually organised within three
      weeks after the operation. It could be visualised in all patients as a region of
      homogeneous, slightly echogenic appearance--not clearly distinguishable from the
      surrounding tissue and not compressible. Areas of low echogenicity were rarely
      seen. The forming of a neo-capsule could be detected from the ninth postoperative
      week onwards. Peri-articular ossification was not seen in this study. A loosening
      of prosthetic material did not occur. In the area of surgical approach
      irregularly shaped slightly echogenic and hardly compressible zones representing
      large haematomas could be found. The volume of these lesions could not be
      measured exactly due to their highly irregular shape. We did not observe large
      areas of seroma or liquid haematoma interfering with the rehabilitation process.
      CONCLUSION: Experienced examiners are capable of demonstrating the sonographic
      features representing signs of the healing process. Thus pathological
      developments can be detected and adequate therapeutic measures be taken. Future
      studies will have to show to which degree ultrasonography can become relevant in
      the diagnosis of endoprosthetic loosening.

PMID- 10929599
TI  - [Measurement of spinal anteflexion in school children by ultrasound topometry].
AB  - AIM: The anteflexion of the spine in normal schoolchildren was examined by 3D
      real-time ultrasound topometry to see if differences in the form of restrictions
      of anteflexion could be detected. METHODS: 102 schoolchildren at the age of 7 to
      9 years volunteered to the study. We measured the spinal anteflexion by recording
      the row of the spines (C7-L5) in a maximally flexed position with a topometric
      digitiser. By computer-aided data analysis the curvature of the spinal line was
      reproduced by lined up radii. RESULTS: In the sagittal plane the spinal line in
      anteflexed position showed a single curvature in 8 cases. In 94 cases the spinal
      line was subdivided into three curvatures (X1, X2, X3) with less mobility of the
      region from the middle to the lower thoracic segments. For these less mobile
      segments we calculated a mean relative anteflexion (X2/[(X1 + X3)/2]) of 0.36 (+/
      0.18). In seven children (6.8%) with clinically indirect signs of scoliosis the
      anteflexion was reduced and in 4 cases out of the standard deviation. For the
      relative anteflexion the Pearson's correlation coefficient of the measurement 1
      and the direct control-measurement was 0.86 (p < 0.001). CONCLUSION: By
      ultrasound topometric measurement of the spinal anteflexion in schoolchildren we
      are able to identify cases with less ability of anteflexion. Because a
      restriction of anteflexion is discussed in the pathogenesis of idiopathic
      scoliosis, a follow up of these children seems to be usefully.

PMID- 10929600
TI  - [Ultrasonographically guided puncture technique for central venous vessels as a
      one-person technique].
AB  - AIM: The traditional anatomic landmark technique usually allows a rapid and easy
      central venous access but this technique is not always successful and can be
      associated with severe complications. We developed an ultrasonically guided one
      operator-catheterization technique whereas a second operator to place and hold
      the ultrasound transducer is not necessary. METHOD: The catheterisation technique
      consists of 3 functional components: the swivel arm, the ultrasound unit and the
      conventional Seldinger central venous catheterization technique. As swivel arm we
      used a device with a 300 mm column with a 700 mm span attached to ultrasound
      unit. There were 234 catheterizations of the internal jugular vein performed in
      the period of January 1999 to July 1999. The indication and complication rate for
      the catheterization procedure was documented. RESULTS: There were 2 plexus
      irritations and 1 hematoma observed in all performed catheterization procedures
      which remained without therapeutic consequences. CONCLUSION: Once the decision
      for central venous access has been made the safest technique should be applied.
      The ultrasonically guided catheterization technique allows a fast, safe and
      convenient central venous access for our patients.

PMID- 10929601
TI  - [Standardized sonographic examination of the hip joint].
AB  - AIM: We demonstrate a technique for examining the hip joint sonographically in a
      standardised way using sectional planes corresponding to the guidelines provided
      by the work group "Sonography of the Musculo-Skeletal System" of the German
      Society of Ultrasound (DEGUM). MRT-scans were used as a comparative standard.
      METHOD: The ultrasound examination was performed in the following standardised
      way: a transversal and longitudinal scan were done in the ventral region and
      additionally a longitudinal scan in the lateral region. In cases without
      pathological findings two standardised planes should be documented. In the case
      of pathological findings the picture should be documented in two standardised
      planes and compared to the corresponding contralateral site. An ultrasound
      examination standardised in this way facilitates a precise assessment of the
      ventral joint capsule, the bone structures, the ventral and lateral aspects of
      the glenoid cavity and the peri-articular soft tissue structures of the hip
      joint. RESULTS: An examination technique is presented which offers additional
      pictorial information, saves costs and is not harmful to the patient. CONCLUSION:
      The ultrasound examination of the hip joint can supply additional information
      about diseases and traumatic changes in this region. In paediatric hip disorders
      such as transient synovitis, septic arthritis, juvenile arthritis, Leg-Calve
      Perthes disease and slipped femoral epiphysis, the ultrasound examination can
      provide important additional information for the initial differential diagnosis
      and during follow-up.

PMID- 10929602
TI  - [Fetal gallbladder and gallstones].
AB  - Fetal anomalies of the gallbladder and fetal gallstones are extremely rare. We
      report a prospective study to assess the gallbladder detection rate according to
      gestational age and the incidence of fetal gallstones. The gallbladder detection
      rate increases from 28.5% below the 16th up to 98% over the 32nd week of
      gestation. We find out a fetal gallstone incidence of 0.07%.

PMID- 10929603
TI  - [The double aorta--rarity or artifact of ultrasound].
AB  - The double aorta is very rare. Only two cases are described in the literature.
      More frequent is a duplication artifact which is misinterpreted as being the
      image of a double aorta. This is caused by a refraction artifact which results
      from the difference in the velocity of sound between muscle tissue and fat
      tissue. Furthermore, a fat depot between parts of the rectus abdominis muscle has
      a prism-like effect. In most cases, this artifact can be avoided by lateral
      shifting of the transducer.

PMID- 10929604
TI  - [Injuries in professional ballet dancing].

PMID- 10929605
TI  - [Artificial knee joints for cross-legged sitting position. Interview by Prof.
      Peter Engelhardt].

PMID- 10929606
TI  - [Problem-oriented learning].

PMID- 10929607
TI  - [Good advice is cheap!--Good advice is expensive! Orthopedic expert rates in the
      internet].

PMID- 10929608
TI  - [Kinetic and kinematic gait analysis before and after total knee endoprosthesis
      implantation].
AB  - OBJECTIVE: The aim of the present paper was to make an objective assessment of
      the surgical outcome after primary knee endoprosthesis implantation by means of
      gait analysis. METHOD: Kinetic and kinematic parameters of gait pattern were
      recorded using multi-component measuring platforms integrated into a treadmill
      and an optoelectric measuring system. 20 patients were investigated
      preoperatively and on average 14 and 28 weeks postoperatively. RESULTS:
      Preoperatively, on the affected side, the leg was used for a shorter time, but
      with much higher maximum forces. Mobility was reduced in the affected joint, in
      the adjacent hip joint, and in the contralateral joints when walking. After
      endoprosthesis implantation, the gait pattern approximated that of the reference
      group. The gait symmetry increased, and the time and force-related loading of the
      operated leg and the extent of mobility of the contralateral knee and both hips
      increased up to 28 weeks postoperatively. The clinical score according to
      Aichroth et al. showed a correlation with the measured values of the gait
      analysis at all times (p < 0.05). CONCLUSION: Mono-articular degenerative changes
      of the knee have a negative effect on the function of adjacent and contralateral
      joints. Endoprosthesis implantation then leads to a normalisation of pathological
      motion patterns, both in the operated and in the adjacent and contralateral
      joints. However, normal values were not yet achieved 28 weeks postoperatively,
      which demonstrates the possibility for further functional improvement depending
      on the continuity of rehabilitation.

PMID- 10929609
TI  - [EMG mapping--applications and results in assessment of muscle coordination
      disorders in patients with a knee endoprosthesis (knee TEP)].
AB  - QUESTION: Disorders of coordination, strength and proprioception are frequently
      described after surgery of the knee joint. These muscular coordination disorders
      have not yet been studied sufficiently. The purpose of this study was the
      objective-quantitative characterization of muscular coordination disorders of the
      M. quadriceps femoris by means of EMG mapping in the arthrotic knee joint and
      their progress after the implantation of a total knee arthroplasty and after in
      patient rehabilitation. METHODS: The extent and pattern of activation (EMG
      mapping) of the M. quadriceps femoris were investigated by means of a 16-channel
      EMG technique in 38 patients before and after the implantation of a total knee
      arthroplasty (type LCS). RESULTS: EMG mapping permitted an objective-quantitative
      characterization of the extent and pattern of activation in the M. quadriceps
      femoris before and after the implantation of a total knee arthroplasty and
      therefore the objectivation of muscular coordination disorders. Muscular
      coordination disorders were present already before surgery and were also caused
      by the implantation of a total knee arthroplasty. These coordination disorders
      can be improved by an inpatient rehabilitation. CONCLUSIONS: The development of
      exercise programs adequate for everyday life is necessary to remove quickly and
      actually the demonstrated coordination disorders.

PMID- 10929610
TI  - [Is unicondylar knee prosthesis a current possibility in primary management of
      varus gonarthrosis?--A prospective matched-pair study].
AB  - AIM: In the present study, we performed a follow-up investigation comparing
      middle-term results after unicompartmental and bicompartmental knee
      arthroplasties. MATERIAL AND METHODS: We used matched pairs with 18 patients in
      each group. The first group was treated with the unicompartmental slegde
      prosthesis (Type Wessinghage), the second with the cementless nonconstrained
      bicondylar prosthesis (Type Natural knee). The mean time of follow-up was 4.5
      years. (SD +/- 0.6). The average age of the patients in both groups was 59 years
      (SD +/- 3). Both groups included 12 female and 8 male patients. All patients
      suffered from primary medial osteoarthritis of the knee. In all cases, the
      contralateral knee also had signs of manifest osteoarthritis. The determination
      and evaluation of the results of the investigation were made according to the
      score of the American Knee Society. We also reviewed the radiological findings
      concerning placement of the prosthesis, radiolucent lines, and patella position
      in the femoral shield. RESULTS: At follow-up examination, there were no
      significant differences in the knee score between the patients undergoing
      unicompartmental or total knee replacement. However, patients with the
      Wessinghage sledge tended to show better results. The mean knee score was 94.3 +/
      4.9 in the Wessinghage group and 91.9 +/- 8.3 in the Natural knee group.
      Evaluation of the radiographs revealed radiolucent lines in the group with total
      replacement. In contrast, in 7 of 18 patients with the unicompartmental
      prostheses we found radiolucent lines at the tibial component of 1 mm or more,
      which, however, did not cause clinical symptoms. CONCLUSION: Our results show,
      that the unicompartmental arthroplasty is still an effective method for the
      treatment of the osteoarthritis, especially concerning the conditions for
      possibly needed revisions.

PMID- 10929611
TI  - [Etiology of early loosening after aseptic cup replacement using allogenic bone
      blocks and cement-free press-fit cups].
AB  - PURPOSE: There are two problems using structural allografts in revision total hip
      surgery. The long-term stability of bulk allografts and the intraoperative
      primary stability of the graft and implant limit the success of this revision
      philosophy. The purpose of this study was to analyse the reasons of early
      loosening of cementless cups after reconstruction with bulk allografts. METHOD:
      In a retrospective study 78 revisions were analysed radiologically. The
      preoperative stage of bone destruction, the size of allografts, the implant
      allograft coverage, and the position of implants were analysed in X-ray series.
      RESULT: There were 12 (15.3%) cases with aseptic and 5 (6%) cases with septic cup
      loosening, after revision surgery, with an average follow-up of 37 (25-84)
      months. All of these failures were registered in the first 12 months
      postoperatively. Large bone defects and an implant-allograft coverage of more
      than 50% are significant (p < 0.001) risk factors of early aseptic loosening.
      CONCLUSIONS: It is important to give careful attentions to primary stability,
      especially in revision total hip arthroplasty using structural allografts and
      cementless cups. For primary stability as well as secondary stability a stable
      fixation with as large as possible areas of contact between implant and living
      bone is necessary. The limit of the method (allograft and cementless cup) is to
      be seen in stage 2B according Paprosky (1990). In larger defects alternative
      reconstruction methods have to be used.

PMID- 10929612
TI  - [Pedestal cup operation in acetabular defects after hip cup loosening. A progress
      report].
AB  - PURPOSE: An extreme extent of acetabular bone loss makes a primary stable cup
      fixation very difficult to achieve. No reliable operation method is as yet
      available. Defect filling with bone cement or bone grafts gives a high long-term
      failure rate. Further revisions are programmed. METHODS: The titanium pedestal
      cup possibly offers a solution to these situations. It is fixed in the load
      carrying upper vital part of the pelvis. A guide is necessary for this step. The
      tapered pedestal is reinforced by two large wings for rotational and structural
      stability. The physiological load transfer goes entirely through the pedestal.
      Thus, the cup serves only for articulation, sometimes without any contact to
      bone. Structural bone grafts are not implanted. Due to its modular length the
      pedestal very often allows a cup position at the original center of rotation.
      RESULTS: A total of 139 pedestal cups have been implanted. Within a prospective
      study 51 hip revisions have been followed over 1-5 years. The indications include
      acetabular defects and resection arthroplasty. Implant related complications were
      few and consisted of a first generation screw failure and malpositioning of the
      pedestal. CLINICAL RELEVANCE: After complete removal of all granulomatous tissue
      and restoration of physiological joint forces we observed early and spontaneous
      bone regeneration. CONCLUSION: We doubt that a bony reconstruction exclusively
      happens after massive bone grafting. The acetabulum can recover even in
      catastrophic cases of pelvic discontinuity without allografts. Nearly all
      revision cases and rim defects can be managed with the pedestal cup.

PMID- 10929613
TI  - [Short-term results of interposition arthroplasty with autologous femur head
      graft combined with cement-free threaded cups for treatment of dysplastic
      coxarthrosis].
AB  - INTRODUCTION: The operative treatment of arthritis in congenital dysplastic hips
      (CDH) with an autologous femoral head graft is a well established technique in
      total joint arthroplasty. This prospective study introduces a new operative
      technique in which the fixation of the autologous bone graft is achieved through
      the threaded Zweymueller cup solely. Early results are presented. METHOD: 34
      patients, (average age of 53.2 years, 24 to 74 years) with CDH had a total joint
      arthroplasty in combination with a femoral head autograft between 1995 and 1997
      (32 patients in study). The fixation of the bone graft was achieved with screws
      or with a press-fit technique through the threaded cup. The results are described
      with an average of 2 years. RESULTS: The patients were followed prospectively for
      an average of 2 years. The Harris hip score increased from 32 preoperatively
      (range 14-61) to 82 (range 54 to 91) postoperatively. 30 hips had excellent and
      good results, one satisfactory and one had an unsatisfactory result. Radiographic
      evaluation demonstrated no osteolysis, one radiolucency was seen in Zone III of
      the acetabulum and heterotopic bone formation was observed in 11 of 31
      radiographically evaluated hips (Brooker type I: 7, type II: 3 and type III: 1).
      All bone grafts achieved union, all grafts survived, and all acetabular
      components survived, but one. There were no complications such as dislocation,
      infection, nerve palsy, or a thrombo-embolic event observed. CONCLUSION: Fixation
      of the femoral head autograft in CDH with a threaded cup solely showed no
      disadvantages over the established fixation technique with screws over a short
      term follow-up. A solid stable fixation of the graft with a threaded Zweymueller
      cup was achieved and resulted in full graft integration without the use of
      screws.

PMID- 10929614
TI  - [An unusual observation of total hip replacement with meta on metal gliding
      bearings].
AB  - QUESTION: The conically clamping inlay of solid metal for the Hofer-Imhof
      threaded socket makes possible the use of a metal-metal-bearing by completely
      dispensing with polyethylen but keeping the four-elements-construction of THR. In
      order to perceive long-term problems and complications patients of our hospital
      who took part in a closed multi-center-study which was established prospectively
      were checked again. METHOD: Clinical and X-ray examination of 27 patients after
      19 months on an average (12-23 months). RESULTS: Harris-score increased from 38
      points before the operation to 89 points three months after the operation and 91
      points in the present check-up. Three months after the operation 22 patients were
      free of pain, at present only 12. X-Rays did not show any signs of loosening
      within the prostheses. But increasing ectopic ossifications of Brooker were
      found: ten times Class I, once Class II and six times Class III. CONCLUSION:
      Using equal form of after treatment the increasing break out of pain as well as
      the growing symptom of ectopic ossifications in the hip area after the
      implantation of the Hofer-Imhof threaded socket with solid metal inlay is
      presumably caused by the use of the metal-metal-bearing as well as by the direct
      lining of the Co-Cr-inlay in the titan-socket and by possible changes in
      corrosion.

PMID- 10929615
TI  - [Individual cement-free total hip endoprosthesis in a patient with a rare form of
      dwarfism (Fuhrmann syndrome)].
AB  - We present a single case study of a 47-year-old female patient with a rare form
      of primary dysostotic dwarfism. This syndrome was first described by Fuhrmann in
      1972. Seven years ago, this patient underwent bilateral cementless total hip
      arthroplasties for severe osteoarthritis about her hips. Custom-made components
      were used. While achondroplastic patients present with wide femoral medullary
      canals, it is clinically relevant that Fuhrmann Syndrome features narrow femoral
      medullary canals. This complicating anatomical factor in Fuhrmann syndrome as
      well as the increased anteversion angles were overcome by the use of CAD stems.
      We conclude that the custom-made stems, although in our case measuring half the
      size of the smallest commercially available design, have proved to be durable and
      able to withstand physiological loads at follow-up period of 72 months.

PMID- 10929617
TI  - [Surgical therapy of hemivertebrae scoliosis and kyphosis--a retrospective
      analysis of 53 cases].
AB  - AIM OF THE STUDY: We performed a retrospective analysis of the results of
      operative treatment of 53 patients with congenital scoliosis (n = 47) or kyphosis
      (n = 6) due to hemivertebrae. PATIENTS AND METHODS: The mean age of the patients
      (31 girls and 22 boys) at the time of the initial examination was 6 +/- 4 years.
      Surgical treatment was carried out on average at the age of 9 +/- 5 years. Follow
      up examinations were carried out up to a mean age of 16 +/- 6 years. RESULTS: The
      results of operative treatment depended on the localization of the hemivertebrae
      and the surgical technique. Progression of scoliosis due to a thoracic
      hemivertebra was halted, but the scoliosis could not be corrected (Cobb angle at
      initial examination 37 +/- 17 degrees at follow-up 34 +/- 23 degrees). Scoliosis
      due to lumbar hemivertebrae was reduced by surgery (Cobb angle at initial
      examination 36 +/- 14 degrees, at follow-up 21 +/- 15 degrees). Surgery without
      instrumentation led to worse results than did surgery with instrumentation with
      thoracic as well as lumbar scoliosis. Combined dorsoventral procedures with
      resection of the hemivertebra seemed to be superior to spondylodesis without
      resection of the hemivertebra. Surgical correction of kyphosis associated with
      dorsal hemivertebrae was performed by means of dorsal or dorsoventral
      spondylodesis with hemivertebra resection (preoperative kyphosis 70 +/- 34
      degrees, at follow-up 44 +/- 25 degrees). CONCLUSION: Spondylodesis without
      instrumentation is associated with an unsure prognosis with respect to effects on
      the progression of the scoliosis, even if it is performed on very young patients.
      In contrast, spondylodesis with instrumentation can achieve better and longer
      lasting corrections of scoliosis even with larger initial curvatures. Scoliosis
      due to lumbar hemivertebrae is more amenable to surgical correction than thoracic
      scoliosis due to hemivertebrae.

PMID- 10929616
TI  - [Results of one-stage endoprosthesis revision in periprosthetic infection cause
      by methicillin-resistant Staphylococcus aureus].
AB  - OBJECTIVE: Are the results of one-stage exchange arthroplasties to treat
      periprosthetic infection caused by methicillin-resistant Staphylococcus aureus
      (MRSA) comparable to bacteriologically unselected studies of one-stage exchange
      operations? METHOD: From 1996 to 1997 twenty patients with a periprosthetic
      infection caused by methicillin-resistant Staphylococcus aureus (MRSA) were
      treated at the ENDO-Klinik by an one-stage exchange arthroplasty. Mean follow-up
      of fifteen one-stage exchange total hip replacements and 5 one-stage exchange
      total knee replacements was 16 months. The patients were examined by means of
      clinical, laboratory-chemical and radiological tests. In addition, postoperative
      joint aspiration was performed on 14 patients. RESULTS: In 11 cases (61%) the
      periprosthetic infection was treated successfully with only one one-stage
      exchange operation. In cases with persisting infection the period between the
      first exchange arthroplasty and the repeated clinical manifestation of the
      infection (second exchange operation) was 2 months on average. 93% of the joint
      aspirations (n = 14), performed on average 4 weeks postoperatively, correlated
      with the result of the follow-up tests. CONCLUSION: Periprosthetic infection with
      MRSA is a problematic infection. Because of the reduced therapeutic possibilities
      it is associated with a higher rate of recurrence than the unselected group of
      patients as a whole [6, 11, 16, 17, 19, 20]. The authors recommend one-stage
      exchange arthroplasty using a combination of vancomycin and ofloxacin as
      admixture to polymethylmethacrylat (Refobacin Palacos R). This procedure does,
      however, need further development. Intraoperative use of an antiseptic and
      systemic administration of rifampicin, as recommended by Zimmerli [23] is a
      further possibility.

PMID- 10929618
TI  - [Ultrasound determination of sacral position in the frontal plane].
AB  - AIM OF THE STUDY: The position of the sacrum in the frontal plane is important
      for the statics of the spine. The most common method of investigating the sacrum
      is its visualisation on an antero-posterior X-ray film. The aim of this study was
      to find a method of determining the position of the sacrum in the frontal plane
      by sonography. METHOD: Criteria for the correct image of the upper rim of the
      sacrum are presented and the procedure for measuring sacral tilt is introduced.
      The results of the sonographic measurements of 107 patients are compared with the
      results of X-ray measurements. The intraindividual differences are described and
      statistically evaluated. RESULTS: Almost 90% of the patients revealed a
      difference between the sonography and the radiology measurement of less than
      three millimeters. The overall sensibility was 80%. The specificity was 82%. The
      results were calculated for different age groups. They turned out to be better in
      children and adolescents than in adult patients. Obese adults had significantly
      worse results than patients with normal body weight. CONCLUSIONS: This study
      suggests that the method presented can help to provide reliable information on
      the position of the sacrum, especially in children and adolescents. By using
      sonography we can partly reduce the necessary X-ray exposure, especially in the
      diagnosis and treatment of leg length discrepancies.

PMID- 10929619
TI  - [Early outcome of correction of hallux valgus with the Scarf osteotomy].
AB  - INTRODUCTION: Aim of this study is to analyze complications as well as clinical
      and radiological results of the scarf osteotomy for the correction of hallux
      valgus. PATIENTS AND METHODS: Between 1994 and 1998 we performed a scarf
      osteotomy for the correction of hallux valgus in 45 cases. Indication was a
      symptomatic hallux valgus with an increased first intermetatarsal angle (IMA).
      Fixation of the osteotomy was performed with two 2.3 mm mini screws made of
      titaneum. Mobilisation was allowed with full weight bearing with a fore foot
      relief orthesis. Clinical results were valued with the fore foot scoring system
      (ffss). The determination of the IMA and hallux valgus angles (HVA) was performed
      with weight bearing d.p. radiographs. RESULTS: All osteotomies healed within the
      first 6 postoperative weeks. Removal of the screws was not necessary in any case.
      The preoperative ffss was 16.2 points. At the last follow up (16 month after
      surgery) the average value of the ffss was 59.1 points. Three patients reached a
      value below 35 points, two of them suffered from a rheumatic disease. Twenty
      patients assessed the cosmetic result as excellent, 16 as good, 4 as satisfactory
      and one as poor. The average IMA could be reduced significantly from 20.2 to 10.3
      degrees. The HVA could be lowered from 37.5 to 20.9 degrees. In patients with an
      IMA of more than 20 degrees the HVA could be reduced to 23.1 degrees in contrast
      to 18.3 in patients with an IMA of less than 20 degrees. DISCUSSION: The scarf
      osteotomiy is a surgical procedure for the correction of hallux valgus due to
      increased IMA which is appropriate in patients younger than 50 years and older
      than 50 years. In cases of IMA more than 20 degrees correction of IMA and HVA was
      unsatisfactory.

PMID- 10929620
TI  - [Resection of the tendon of the peroneal brevis muscle in "clicking" peroneal
      tendons--a report of 3 cases].
AB  - INTRODUCTION: The following article deals with the problem of peroneal clicking.
      This means a clicking of the two peroneal tendons against each other. It has to
      be differentiated from peroneal tendon dislocation or subluxation. METHOD: In
      three patients, a peroneal click was found without symptoms of dislocation of the
      tendons over the fibula. In these cases the indication for resection of the
      peroneal brevis tendon was seen. RESULTS: Postoperatively no pain, swelling, and
      peroneal click were present. The partial loss of function of the peroneal brevis
      tendon seems to be negligible. CONCLUSION: In case of pain and swelling over the
      peroneal tendons, peroneal clicking should be included in a differential
      diagnosis. Resection of the peroneal brevis tendon is an effective treatment in
      these cases.

PMID- 10929621
TI  - [Standardized ultrasound diagnosis (13 MHz) of the tendon of the posterior tibial
      muscle--normal findings in probands with healthy feet].
AB  - OBJECTIVES: Tibialis posterior dysfunction is often diagnosed at a very late
      stage. However, the early diagnosis of tibialis posterior dysfunction is crucial
      for therapeutic aspects and especially for the operative prognosis. The
      morphological correlate of the tibialis posterior dysfunction consists of
      degenerative changes and thickening of the posterior tibial tendon [2, 9, 11]. By
      means of a high frequency linear array transducer, a standardized technique of
      examination as well as reference values of cross-sections of posterior tibial
      tendon are introduced. MATERIAL AND METHODS: Investigating 51 healthy subjects
      (102 feet) without any foot deformities, standardized planes were defined by use
      of a 13 MHz linear array transducer in order to delineate the posterior tibial
      tendon. At exact anatomic landmarks, tendon diameters were measured using two
      longitudinal sections proximal and distal to the medial malleolus. Likewise, two
      diameters and the resulting roughly calculated cross-section of the tendon were
      determined, using two transverse sections at the level of the subtalar joint
      facet and the medial malleolus. The findings obtained by ultrasound in four
      female patients with the diagnosis of a tibialis posterior dysfunction confirmed
      during surgery are compared to the aforementioned 51 healthy subjects. RESULTS: A
      healthy tendon appears homogeneous and echo-rich in orthogonal ultrasound and
      displays average areas of 18.4 sq.mm. (SD 5.9 sq.mm.) at the subtalar joint facet
      level and 19.2 sq.mm (SD 4.8 sq.mm.) at medial malleolus level in transverse
      sections. The corresponding areas obtained in patients with tibialis posterior
      dysfunction were clearly enlarged than in healthy subjects. In 85% of all feet
      examined at the level of the medial malleolus, the tendon is surrounded by a
      hypoechoic halo which has a size smaller than two times the cross-section of the
      flexor digitorum longus tendon. CONCLUSION AND CLINICAL RELEVANCE: Reference
      values of tendon thickness and of intratendinous echo-structures at reproducible
      landmarks facilitate delimitations from pathological tendon alterations. The
      exact delineation of intratendineal echoes by high frequency array transducers
      and standardized examination techniques that measure tendons size is a
      prerequisite to enable an early assessment and registration of degenerative
      alterations and thickening of the posterior tibial tendon.

PMID- 10929622
TI  - [Biomechanics and evaluation of the microprocessor-controlled C-Leg exoprosthesis
      knee joint].
AB  - QUESTION: Also in the field of technical orthopedics, electronics and computer
      technology are being is used more and more often. This paper describes a
      microprocessor-controlled prosthetic knee joint with swing phase control and
      stance phase stability, the so-called C-Leg. The function of this electronic knee
      joint is explained. Prosthetic treatment using the C-Leg is compared with
      traditional prosthetic knee joints. METHOD: 15 patients using the C-Leg have been
      observed over periods of 6 to 14 months. The treating prosthetists have given an
      assessment regarding the function and the improvements in comparison with the
      previously fitted knee joints. The patients, too, were asked to compare function
      and comfort of the new prosthetic fitting with the previous one. RESULTS: Both,
      prosthetists and patients marked this new type of microprocessor-controlled knee
      joint in nearly all points with "very good" and described a clear improvement to
      the previous, purely mechanical prosthetic fitting. CONCLUSIONS: Obviously, this
      new technology seems to be a milestone in prosthetic knee joint fitting, in order
      to clearly improve the prosthetic fitting of transfemoral amputees and thus their
      quality of life, especially of people who have several disabilities.

PMID- 10929623
TI  - [Barrett esophagus].

PMID- 10929624
TI  - [Epidemiology and pathophysiology of Barrett esophagus].
AB  - The pathophysiology of Barrett's esophagus appears to be a sequential process;
      the squamous epithelium of the esophagus is replaced by multipotent
      undifferentiated cells; secondary to cellular damage in the course of
      gastroesophageal reflux disease these undifferentiated cells further
      differentiate under the ongoing influence of mucosal damage, thus forming the
      typical morphology of Barrett mucosa. While the prevalence of gastroesophageal
      reflux disease amounts to 10% to 30%, the prevalence of Barrett's esophagus is
      estimated to be 1% in the general population. The epidemiologic data of Barrett's
      esophagus gain special attention with regard to the fact that the specialized
      columnar epithelium with intestinal metaplasia represents the only recognized
      risk factor for the development of adenocarcinoma in the esophagus. Currently it
      is estimated that the risk of the development of an adenocarcinoma on the basis
      of Barrett's esophagus is about 30-50 fold higher than that in the general
      population.

PMID- 10929625
TI  - [Diagnosis of gastroesophageal reflux and Barrett esophagus].
AB  - Gastroesophageal reflux is a very common disorder. Typical symptoms are
      heartburn, regurgitation and chest pain. Recently, it has been demonstrated that
      gastroesophageal reflux may generate or worse extraesophageal symptoms such as
      asthma, chronic bronchitis, posterior laryngitis, and chronic cough. The
      diagnosis of gastroesophageal reflux is suggested by typical symptoms which
      improve under a therapy with proton pump inhibitors. pH-monitoring over 24 hours
      is able to establish directly the diagnosis by measuring acid reflux into the
      esophagus. Manometry detects the two most common causes of gastroesophageal
      reflux: insufficiency of the lower esophageal sphincter or esophageal motility
      abnormalities. Gastroesophageal reflux can lead to reflux esophagitis, which is
      diagnosed endoscopically. An endoscopy should routinely be performed in case of
      dysphagia, anemia, or loss of weight. A long-term sequela of gastroesophageal
      reflux is the development of Barrett's-esophagus, a condition which has to be
      verified by endoscopy and biopsy. This premalignant lesion is defined by a
      metaplastic change from the normal squamous mucosa to a specialized intestinal
      epithelium characterized by goblet cells. Because dysplasia in these metaplastic
      areas can lead to esophageal adenocarcinoma, regular endoscopic surveillance with
      biopsies is recommended. Gastroesophageal reflux can significantly impair the
      quality of life and can cause complications that include the neoplastic
      progression from Barrett's esophagus to carcinoma. Therefore, appropriate
      diagnostic procedures and adequate therapy are required. This article summarizes
      the diagnostic approach to patients with gastroesophageal reflux, reflux
      esophagitis and Barrett's-esophagus. The impact of endoscopy, pH-monitoring,
      esophageal manometry, radiology and scintigraphy are reviewed.

PMID- 10929626
TI  - [Are screening programs in Barrett esophagus meaningful?].
AB  - This review analyses whether the assumption is justified that endoscopic
      screening in patients with Barrett's syndrome facilitates early recognition of
      cancer and leads to prolongation of life. It is shown that no reliable data exist
      that would support the latter conclusion. Although there is scant information
      that some patients may benefit from close surveillance, it appears unlikely that
      an all too ambitious surveillance program will either be cost effective or
      acceptable for patients and/or endoscopy centers.

PMID- 10929628
TI  - [Endoscopic argon plasma coagulation of Barrett mucosa].
AB  - BACKGROUND: Up to 10% of patients with Barrett's esophagus develop adenocarcinoma
      of the distal esophagus. Endoscopic surveillance is recommended. We studied the
      potential of Argon plasma coagulation (APC) for eradication of Barrett's
      esophagus. METHODS: Indication for APC was the histologic evidence of columnar
      epithelium with a length of > or = 2 cm, located proximal of the cardia and with
      the presence of goblet cells. Endoscopic therapy was performed using an
      Argonbeamer (Beamer 2, Erbe Company, Tubingen, Germany) under i.v. sedation and
      repeated in intervals of 2-3 weeks with the aim of complete eradication of
      Barrett's epithelium. One month after macroscopic Barrett eradication,
      superficial and deep biopsies were obtained every 2 cm in 4 quadrant technique to
      confirm the endoscopic aspect of complete eradication. RESULTS: We report our
      results (follow-up median: 12 mths., 3-25) in the first 12 patients (8m/4f,
      median age 57 yrs., 42-69) in which treatment was completed. In one case there
      was evidence of moderate dysplasia. A mean of 5 (4-11) sessions were required for
      complete Barrett eradication in 11 patients (median size of Barrett-segment: 4
      cm, range 2-11), in one patient partial regression of 50% was observed treatment
      was discontinued after 17 sessions while only. Deep biopsies showed subepithelial
      columnar epithelium islands in one case, recurrence of Barrett occurred in 2
      cases after 3 and 6 months. Under APC-treatment, 11/12 patients complained about
      retrosternal pain and odynophagia. No other complications were observed.
      CONCLUSION: Our preliminary results indicate that APC is safe and effective to
      eradicate Barrett's epithelium. Follow-up in a larger number of patients is
      necessary to assess longterm results (Barrett recurrence, decrease in the
      incidence of the adenocarcinoma), before APC may generally be recommended.

PMID- 10929627
TI  - [Conservative and surgical antireflux therapy as prevention of carcinoma].
AB  - INTRODUCTION: Based on findings in literature, the effectiveness of the medical
      versus operative antireflux therapy was examined as a prophylaxis to impede the
      formation of an adenocarcinoma in the case of Barrett esophagus. MEDICAL
      ANTIREFLUX THERAPY: Despite reports of success following the administration of
      Omeprazole, the inhibition of acid secretion does not lead to the regression of
      the endobrachyesophagus for most patients. The partial shortening of the Barrett
      segment is reported in up to 78% of cases, however the precancerous changes of
      the distal esophagus are not eliminated. In spite of medical therapy with proton
      pump inhibitors, up to 6% of dysplasias become metaplasias per year. In 3% of the
      patients, an adenocarcinoma arises. OPERATIVE ANTIREFLUX THERAPY: It is reported
      in the literature that there is a partial regression of the endobrachyesophagus
      in up to 34% of cases and complete regression in up to 11% of cases following
      operative antireflux therapy. Despite a macroscopically unchanged Barrett segment
      following a fundoplication or semifundoplication procedure, a complete regression
      of minor dysplasias and the complete regression of intestinal metaplasias is
      possible. In only 30% of patients, postoperative atypical findings were
      ascertainable. Nevertheless, a severe change can appear in the cylinder
      epithelium of the remaining Barrett segment following an operative antireflux
      therapy, up to the formation of an adenocarcinoma (1-9%). For this reason, the
      patients must be endoscopically and histologically examined at regular intervals
      following the antireflux operation. CONCLUSION: In the case of evidence of severe
      dysplasias in the Barrett segment, the attempt at carcinoma prophylaxis by means
      of antireflux therapy is no longer indicated. With the appearance of mild
      dysplasias and complete intestinal metaplasias in the Barrett esophagus, an
      antireflux operation can lead to a reduction in the grade of atypical cells. In
      cases of existing metaplasia or the presence of mild dysplasias, the
      administration of proton pump inhibitors or H2 blockers is only indicated as a
      symptomatic therapy.

PMID- 10929629
TI  - [Surgical treatment of Barrett carcinoma].
AB  - Barrett-carcinoma is a type of adenocarcinoma of the distal esophagus and the
      cardia. Barrett-esophagus is defined by the histologic presence of specialized
      epithelium with intestinal metaplasia. As a consequence Barrett-carcinoma has a
      close relationship to the adenocarcinoma of the cardia and is very often part of
      the cardiacarcinoma type I. The aim of the surgical therapy is a radical R0
      resection of the tumor including the lymphatic drainage area. This aim is
      accomplished among different authors by different surgical concepts. One is the
      radical transhiatal subtotal esophagectomy with lymphadenectomy in the lower
      mediastinum and the upper abdominal compartments. The other concept is a
      transthoracic en-bloc esophagectomy. Both resection procedures are usually
      completed by gastric pull up reconstruction. Currently a sophisticated
      preoperative staging is followed by distinguished indication and therapy
      depending on tumor status, risk factors of the patient and on the international
      classification of the cardia carcinoma (Siewert). When a R0-resection is
      impossible, a neoadjuvant radiochemotherapy should be performed.

PMID- 10929630
TI  - [Ciprofloxacin levels in pleural fluid and serum during systemic administration
      after pneumonectomy].
AB  - Postpneumonectomy empyema represents a frequently lethal complication. It remains
      unsolved whether prophylactic antibiotics achieve a bactericidal concentration in
      the pleural cavity after pneumonectomy. 12 patients undergoing pneumonectomy
      received ciprofloxacin intravenously (2 x 200 micrograms/d) and orally (2 x 500
      micromilligrams/d) during the first and second postoperative week, respectively.
      1, 6, 9 and 14 days after the operation the ciprofloxacin concentration was
      measured in the pleural fluid and serum. Already after 24 hours bactericidal
      levels (0.56 microgram/ml) were found in the pleural fluid, rising to 1.11
      micrograms/ml on day 14 under the higher oral dosage. Thus, it could be
      demonstrated that during the first two weeks after pneumonectomy high
      concentrations of an antibiotic similar to the levels in the serum can be
      achieved in the pleural fluid.

PMID- 10929631
TI  - [Stage-adapted therapy of pleural empyema. Results during 1992-1998].
AB  - Despite the decreasing number of patients suffering tuberculosis and the use of
      modern broad spectrum antibiotics the pleural empyema did not lose its relevance.
      The main reasons are increasing numbers of patients with drug and alcohol abuse
      or immunodeficiency of different causes. We retrospectively analysed the data of
      73 patients treated of pleural empyema between 1992 and 1998. Considering the
      known stages of pleural empyema we present the corresponding therapeutic results.
      All patients classified as stage I were treated with a chest drain and cure was
      achieved in all of them (100%). The treatment for patients classified as stage II
      was different: 5 out of 32 were treated with a continuous irrigation and suction
      chest drain system. 18 patients first underwent thoracoscopy and were afterwards
      treated with a continuous irrigation and suction system. Another 9 patients
      primarily underwent an early open decortication. In 40% the treatment with the
      suction and irrigation system was successful. Using video-assisted thoracoscopy
      (VATS) cure was achieved in 94.4%, with open decortication in 100%. The preferred
      treatment of patients classified as stage III is the open decortication. After
      the first operation 80% (30 patients) were cured. 6 patients needed
      thoracoplastic procedures after the first intervention. No patient was discharged
      neither with a permanent chest drain nor a permanent thoracic window. With the
      results a cause dependent analysis of morbidity and mortality was done. The
      overall morbidity rate was 27.9% and the overall mortality 5.4%. The treatment of
      pleural empyema still remains to be problematic. Corresponding to our results
      pleural empyema classified as stage I is best treated with a simple chest tube.
      The video-assisted thoracoscopy (VATS) lacks of complications and is a very
      efficient method in treating stage II. The method of choice in stage III is the
      open decortication which in the case of a chronic and recurrent or persistent
      infection should be followed by a thoracoplastic procedure.

PMID- 10929632
TI  - [Postoperative peripheral neuropathies in general surgery].
AB  - INTRODUCTION: Postoperative nerve lesions beyond the operative area, the so
      called positioning traumas are considered uncommon in general surgery. But they
      can have serious consequences for the patient and the surgeon, including forensic
      sequelae. The objective of this work was to describe the incidence, pattern, risk
      factors and course of postoperative neuropathies in general surgery and to
      identify indicators to prevent these complications. METHODS: Based on neurologic
      records we reviewed all postoperative peripheral neuropathies that occurred in
      the Department of General Surgery of the University Hospital Freiburg in the time
      period from January 1979 to December 1990. Lesions that occurred as a direct
      operative effect were excluded. RESULTS: In 35 patients 50 nerve lesions were
      observed, representing an incidence of 0.12% of all operations during this time
      period. Most frequently lesions of the n. peroneus occurred, followed by the n.
      ulnaris, n. cutaneous femoris lateralis and n. medianus. Nerve lesions were
      observed in every body position and as early as after 15 min. Postoperative nerve
      lesions have a favorable prognosis. DISCUSSION: Nerve lesions caused by
      positioning can occur during any operation with any duration in general surgery.
      They should be avoided by thorough and careful positioning. Also the patient must
      be informed about the possibility of nerve lesions caused by the positioning.

PMID- 10929633
TI  - [Traumatic rupture of the pancreas and duodenum in pre-existing penetrating
      duodenal ulcer].
AB  - Pancreatic injuries are rare complications after blunt abdominal trauma and
      usually the result of a direct force separating the pancreatic body in front of
      the vertebral column. This case report describes the uncommon event of a severe
      pancreatic and duodenal injury (stage IV b of Lukas) in which the combination of
      a direct force and the setting of a preexisting penetrating ulcer of the duodenum
      caused the extent of the pancreatic and duodenal injury [9]. Because of the
      preexisting lesion a Whipple procedure had to be performed. This case report
      demonstrates the influence of chronic abdominal diseases on the outcome of blunt
      abdominal trauma.

PMID- 10929634
TI  - [Cecal diverticulitis].
AB  - INTRODUCTION: Cecal diverticulitis is an important differential diagnosis to
      acute appendicitis. The diagnosis is often difficult to make and the therapeutic
      procedure is still a point of discussion. PATIENTS AND METHOD: Seven patients (24
      77 years old) who underwent surgery for abdominal reasons were investigated
      retrospectively. RESULTS: Five patients who had not underwent appendectomy before
      were operated under the leading diagnosis of acute appendicitis. Despite further
      diagnostic measures, only in one case of the two patients who had already had an
      appendectomy before, the diagnosis cecal diverticulitis could be made
      preoperatively. DISCUSSION: Preoperative diagnostics, if conducted at all, only
      rarely lead to the diagnosis of cecal diverticulitis. In prolonged courses and in
      patients after appendectomy, laparoscopy can be of diagnostic and therapeutic
      value. If it is possible to diagnose cecal diverticulitis preoperatively,
      conservative treatment can be indicated. If the diagnosis is made
      intraoperatively and malignancy can be securely excluded, we recommend ileocecal
      resection, but not appendectomy and further conservative treatment. If a
      carcinoma can not be excluded definitively, a hemicolectomy must be performed.

PMID- 10929635
TI  - [Observations on traditional healers ("medicine men") of Indonesian aborigines].
AB  - The observations were done during expeditions to tribes of Indonesian aborigines
      on the islands of New Guinea/Irian Jaya (Korowai-tribe) and Borneo/Kalimantan
      (Benuaq-tribe). Neither the Korowai people, who are still living under stone age
      like circumstances in up to 30 m high tree-houses, nor the Benuaq people of
      Borneo, being already influenced by missionary men, do treat injuries or wounds
      by traditional healers. All the "internal" disorders, not being suffered by
      injuries, are diagnosed and treated in certain ceremonies, during which the
      healer tries to get in contact to the spirits triggering the disease. The idea is
      to know the reason of the disorder caused by demons, though the patient can be
      treated with bringing offerings or confirmations. This way of treating is due to
      the image of a magic-demoniac relationship between patient and his disease.

PMID- 10929636
TI  - [Principles of surgical oncology. I].

PMID- 10929637
TI  - [Current concepts of metastasis classification].
AB  - New findings of molecular pathology provide better insight in the process of
      metastasis. Single findings in few patients are, however, useful in being taken
      as parameters which signalize the individual risk of a metastasis not detectable
      by clinical methods. In addition they cannot be used as prognostic factors. On
      the other hand, there are important data which indicate a prognostic significance
      of so called isolated tumour cells, which can be detected by cytological or
      molecular methods. Current and proposed classifications of metastasis reflect the
      necessity, to better describe the situation of an individual patient to design an
      optimal therapy. Such more exact classifications will form the basis of a more
      differentiated therapy and will give more exact data to estimate prognosis.

PMID- 10929639
TI  - [Hereditary carcinoma: pathogenesis and diagnosis].
AB  - Effective prevention of cancer in patients with a hereditary disposition to
      malignant tumours was made possible by intensive prevention programs and
      molecular diagnosis. Taken hereditary non-polyposis colorectal cancer (HNPCC) as
      an example this article deals with the pathogenesis and molecular diagnosis in
      hereditary dispositions to cancer. HNPCC is inherited in an autosomal-dominant
      fashion and caused by germline mutations in genes responsible for detection an
      removal of DNA-basepair-mismatches (DNA-mismatch-repair-genes). The error rate in
      DNA replication is reduced thousandfold by these genes. A defective DNA-mismatch
      repair results in tumours if the increased mutation rate causes alterations of
      tumour-suppressor- or oncogenes. HNPCC patients develop colorectal cancer but
      also tumours of the renal pelvis, the ureter, the small bowel, the endometrium
      and less often in other organs. The clinical presentation of these tumours may be
      characteristic, the clinical diagnosis may be guided by different clinical
      criteria catalogues. The suspicion is proven by the identification of a germline
      mutation in DNA-mismatch-repair-genes. This laborious diagnostic procedure is
      often preceded by prescreening procedures as the detection of microsatellite
      instability or immunohistochemical tests. Once the germline mutation is
      identified in a affected family member, the first degree relatives may be tested
      for this mutation. If they have inherited the mutation, they harbour a extremely
      high risk for developing cancer and therefore may be included in prevention
      programs. This so called predictive testing must be preceded by genetic
      counseling.

PMID- 10929638
TI  - [Effect of nutrition factors on the pathogenesis of colorectal carcinoma].
AB  - There is convincing evidence that nutrition affects colorectal carcinogenesis in
      a complex fashion. Dietary components either promote or inhibit the carcinogenic
      process. The composition of dietary fats seems to be less important as a
      promoting factor than a positive energy balance, especially in combination with
      low physical activity. Excessive consumption of red meat is associated with
      increased risk, which may be due to the heme contained in myoglobin. Alcohol
      stimulates cell proliferation in the rectum and may thus increase cancer risk.
      Complex carbohydrates (e.g., dietary fiber) are degraded in the colon to short
      chain fatty acids which exhibit protective effects in experimental models of
      carcinogenesis. The putative protection from vitamins and trace elements merits
      further attention.

PMID- 10929640
TI  - [Deregulation of intracellular signal pathways in colorectal carcinoma].
AB  - The analysis of the genetic causes of tumor development led to the identification
      of many genes affected in these diseases, which play a role in the control of
      cell proliferation and apoptosis. However, these studies also suggested that not
      all alterations are equal with regard to their effect on tumor growth, and they
      demonstrated that the deregulation of the classical cytoplasmic cascade made up
      by Ras-Raf-MEK and ERK plays a critical role in tumor development. These findings
      also raise the hope that via interference with a single pathway growth of a tumor
      carrying multiple genetic alterations will be affected.

PMID- 10929642
TI  - [Surgery of hereditary colorectal carcinoma].
AB  - Hereditary colorectal cancer syndromes account for about 7% of all colorectal
      carcinomas. The most frequent form is Hereditary Nonpolyposis Colorectal Cancer
      (HNPCC). Identification, cloning and sequence analysis of the predisposing genes
      enables identification of mutation carriers and non-mutation carriers,
      respectively. These genetic informations can be used in an individually tailored
      clinical surveillance program and may ultimately result in standard preventive
      surgical treatment. In classical FAP the surgical standard is performing a
      restorative proctocolectomy. It is still unclear now, if this procedure should be
      modified in attenuated forms (colectomy with ileorectostomy). Due to a high rate
      of synchronous and metachronous carcinomas a subtotal colectomy in the case of
      first colon cancer seems to be indicated in HNPCC patients. A proctocolectomy or
      a restorative proctocolectomy should be weighed in case of carcinomas in the
      lower rectum. These procedures should be performed under the precondition of
      identification of the pathogenic germline mutation in the patient, only. In
      addition, a synchronous prophylactic hysterectomy with oophorectomy should be
      recommended postmenopausal gene carriers. Intensive counseling of the patient
      should proceed these preventive procedures involving surgeons,
      gastroenterologists, geneticists, molecular biologists, gynecologists, physicians
      and psychologists. It is recommended to have patients treated exclusively in
      specialized centers. Currently, six interdisciplinary centers for cancer
      surveillance and early diagnosis in hereditary colorectal cancer are being
      sponsored in Germany by the Deutsche Krebshilfe since 1999. In the future
      clinical studies have to be conducted to evaluate the efficacy of extended
      colorectal resections versus efficacy of surveillance and conventional resections
      according to general oncological principles.

PMID- 10929641
TI  - [Diagnosis and significance of minimal residual disease in patients with
      colorectal carcinoma].
AB  - Progression of malignant tumours to metastatic disease after surgery in curative
      intent is due to usually few and with conventional diagnostic techniques
      undetectable residual malignant cells. These cells must have been spread either
      before or during surgery. The more sensitive and specific detection of these
      malignant cells in various clinically relevant compartments of the patients
      organism became possible through new immunocytochemical and molecular tools.
      Various clinical studies underline the strong prognostic impact of the detection
      of disseminated cancer cells. However, many technical aspects did not yet allow
      sufficient standardization of these procedures and led to significantly varying
      results among different scientific groups. It is one of our primary aims to test,
      whether the detection of disseminated cancer cells might guide the indication for
      adjuvant therapies and might predict the efficacy of therapies in patients with
      solid cancers.

PMID- 10929643
TI  - [Results of radiotherapy in rectal carcinoma].
AB  - Adjuvant combined radio-chemotherapy in rectal cancer is indicated in stage UICC
      II and III (pT3/4 and/or pN+) without distant metastases (exception: resectable
      metastases of the liver). Radiotherapy alone improves local control in the
      pelvis. A statistical significant improvement of survival is only achievable in
      combination with systemic chemotherapy. In Germany neo-adjuvant, conventional
      fractionated radio-chemotherapy over five weeks is applied in patients with
      surgically inoperable tumors to achieve a "down-staging" with improvement of
      resectability. Neo-adjuvant radiotherapy of operable rectal cancer in five
      fractions of high single doses within one week has revealed a statistical
      significant improvement of survival if compared to surgery alone in the Swedish
      rectal cancer trial, but is not standard in Germany yet. The influence of
      technical advances in surgery as total mesorectal excision (TME) on indications
      of adjuvant therapy is evaluated in prospective randomized studies at this time.

PMID- 10929644
TI  - [Anti-tumor vaccination].
AB  - Five year survival rates are presented for 32 primary operated breast cancer
      patients who were postoperatively treated with an optimal dose of autologous NDV
      modified tumor vaccine. Their overall survival and their recurrent-free survival
      was significantly better than that of 31 comparable breast cancer patients
      treated simultaneously with a suboptimal dose of the same type of vaccine. The
      concept, development and mechanism of action of this vaccine are als commented
      on.

PMID- 10929645
TI  - [Adjuvant immunotherapy of stomach carcinoma with antibody-induced apoptosis].
AB  - The human monoclonal antibody SC-1 was isolated from a patient with a diffuse
      type adenocarcinoma of the stomach and induces apoptosis of stomach carcinoma
      cells by binding a stomach-carcinoma-associated isoform of CD55/DAF-B. In a first
      clinical trial with 20 patients with poorly differentiated stomach adenocarcinoma
      of diffuse-type received 20 and 30 mg of purified SC-1 antibody intravenously,
      followed 24 or 48 h later by gastrectomy and lymphadenectomy. In 90% of the cases
      a significant induction of apoptotic activity was measured in primary tumors as
      compared with earlier biopsy material and in 50% of the patients a significant
      regression of tumor mass could even be determined histopathologically. No toxic
      crossreactivity was observed with normal tissue or organs of patients. These data
      show, that the human monoclonal antibody SC-1, which induces tumorspecific
      apoptosis, can be successfully used for adjuvant therapy.

PMID- 10929646
TI  - [Gene therapy of malignant tumors].
AB  - New techniques in molecular biology and increasing insights in the genetic basis
      of tumorigenesis led to the development of therapeutic agents composed of genetic
      information. The majority of gene therapy trials is targeted towards cancer
      therapy. The most frequently used strategy is immunotherapy which comprises
      transfer of genes encoding cytokines, costimulatory molecules or tumorspecific
      antigens to enable cells of the immune system to identify and destroy tumor
      cells. The second important strategy makes use of suicide genes to selectively
      kill tumor cells. Compensation of genetic defects by the downregulation of
      activated oncogenes or the restoration of tumor suppressor gene functions is the
      third concept to revert the malignant phenotype of cancer cells.

PMID- 10929647
TI  - [The role of growth factors in wound healing].
AB  - Growth factors are mediators with essential importance for undisturbed repair
      process after wounding. The well coordinated concert of these substances is
      necessary for healing with complete restoration of function and morphology. These
      complex mechanisms are disturbed during secondary and delayed repair. The result
      is protracted healing course and inferior scar quality--either hypo- or
      hypertrophic. Local and systemic application of these growth factors seems to add
      important instruments for therapeutic use in the treatment of chronic wounds.
      Knowledge from experimental research is encouraging, although the exact
      mechanisms of synergistic action are not completely understood. However, the
      results from clinical use in controlled studies do not meet these expectations by
      far. The main reasons for this dilemma are thought to be little understanding in
      the complex interactions of these substances. In fact, different wound entities
      seem to reveal different cytokine profiles during the course of repair. Further
      intensive research therefore is required for the rational use of growth factors
      in the clinical setting.

PMID- 10929648
TI  - [Role of chemokines in human skin wound healing].
AB  - The healing process of skin wounds is regulated by growth factors which stimulate
      proliferation of resident cells and their synthesis of extra cellular
      matrixcomponents. Different leukocyte subtypes (neutrophils, macrophages,
      lymphocytes and mast cells) participate in wound healing not only as
      immunological effector cells but also as an important source of inflammatory and
      growth promoting cytokines. Rapid recruitment of leukocytes and their positioning
      is tightly regulated by a temporally and spatially changing set of chemokines.
      Whereas expression of IL-8 and GRO (growth related oncogene) direct early
      neutrophil recruitment, migration of macrophages is stimulated by MCP-1 (monocyte
      chemoattractant protein-1) and later, lymphocytes are attracted by IP-10 (gamma
      interferon inducible protein-10) and Mig (monokine induced by interferon-gamma).
      Since chemokines as IL-8 and GRO also stimulate angiogenesis and keratinocyte
      proliferation, they integrate the inflammatory events with the reparative
      processes and are potential candidates in the search of wound healing agents.

PMID- 10929649
TI  - [Possibilities of demonstration of growth factors in chronic wounds.
      Demonstration of RNA and protein in wound tissue].
AB  - Growth factors are important modulators of wound healing. So far, there is little
      clinical data showing that healing defects in chronic wounds are attribute to
      deficiency of growth factor expression. Characterization of growth factor
      expression is necessary to provide new directions toward developing therapies in
      treating wounds. Present available molecular and immunological techniques allow
      the analysis of mRNA and protein expression in small amounts of wound material.
      We analyzed growth factor expression in wound tissue and wound fluid from acute
      and secondary healing wounds. Wound tissue of secondary healing wounds reveals a
      higher mRNA growth factor expression compared to acute wound tissue. Secondary
      healing wounds from our studies demonstrated no deficiency of growth factor
      expression however, functional analysis may be necessary to determine their
      activity.

PMID- 10929650
TI  - [Clinical application of growth factors and cytokines in wound healing].
AB  - The clinical value of growth factor treatment of chronic wounds has yet to be
      determined. Beneficial effects have been reported so far only from specialized
      wound care centers where growth factors supplemented the results achieved with
      good wound care. In general optimization of current methods of external wound
      care, adequate metabolic and nutritional control and surgical measures should be
      employed before any adjuvant growth factor therapy is attempted. Current use of
      exogenously applied growth factors and cytokines appears to be reasonable only in
      the setting of controlled clinical studies according to the rules of "good
      clinical practice". With more knowledge on the biology of chronic wounds and
      progress in wound pharmacology the best application for these peptides will have
      to be reevaluated.

PMID- 10929651
TI  - [Tissue engineering: possibilities and perspectives].
AB  - Successful tissue engineering requires intensive co-oporation between clinicians,
      biologists (cell culture, gene therapy), chemical engineers (biomaterials) and
      industrial partners. In case of wound healing tissue engineered constructs have
      already been applied successfully in burns and chronic wounds. In order to
      improve carrier and matrix function biomaterials still have to be optimized. The
      potential of such constructs might even be enhanced by gene therapeutical
      methods. The complex mammalian organism has to be considered as the gold standard
      and the model for perfect tissue engineering. The problem of vascularization of
      complex organs yet has to be solved. In general it seems to be more promising to
      substitute deficient components in vivo and to rely on modulating influences
      within the host organism rather than to create complex organs ex vivo.

PMID- 10929652
TI  - [Gene therapy perspectives in modulation of wound healing].
AB  - A variety of reasons can afflict wound healing. Current research is focussed on
      the acceleration of wound healing by stimulating molecular processes. Gene
      therapy may offer completely new ways to treat chronic wounds. Possible
      advantages of gene therapeutic modulation of wound healing might be a long term
      efficiency, systemic or local regulation of gene expression and low side-effects.
      Current goals comprise the improvement of transfection efficiency and
      specificity. In vivo applications are therefore focussed on optimized inducible
      or even cell-type specific promotors, as well as on improved local application
      techniques. Studies from our laboratory demonstrate the possibility to combine
      modern cell culture techniques with different types of gene transfer. This
      enables the simultaneous grafting of manipulated cells to the wound with the
      continuous delivery of specific proteins of interest. Experimentally, this lead
      to accelerated closure of partial and full thickness animal wounds. Clinically,
      gene therapy for the treatment of chronic wounds seems to be a realistic goal
      within the next years and might be applicable for a variety of novel indications.

PMID- 10929653
TI  - [Treatment of chronic wounds with cultured autologous keratinocytes as suspension
      in fibrin glue].
AB  - Cultivated keratinocytes have been used for treatment of chronic wounds. Our
      group developed a new application form, using a suspension of subconfluently
      cultivated keratinocytes in fibrin glue (keratinocyte-fibrin-glue-suspension =
      KFGS), which has successfully been used in burn patients. Altogether 8 patients
      (average: 57 yrs.) with complex chronic wounds of different origin were treated
      with KFGS. All wounds, which had been existing from 4 months to 14 years, showed
      good reepithelization. Up to now there has been observed stable wound closure for
      4 years after grafting. This study demonstrates the wound healing potency of a
      keratinocyte-fibrin-glue-suspension also for chronic wounds. Fibrin glue seems to
      be both an ideal application vehicle as a biological matrix for the cultivated
      keratinocytes. The transplantation of cultivated autologous keratinocytes as
      suspension in fibrin glue is a promising way in the treatment of chronic wounds.

PMID- 10929654
TI  - [From the history of wound care].
AB  - Wound care in ancient times was based on many techniques: Bandages soaked with
      antibiotics, Sutures continuous or in separate stitches, apply of poultices
      around the wounds, honey and propolis as antibiotics in the treatment of wounds,
      surgical drainage of pus with a piece of tin pipe etc. The oldest wound clamp is
      shown with the jaws of ants holding together the edges of a wound. Finally are
      discussed the cauterization and the principles of Antisepsis and Asepsis.

PMID- 10929655
TI  - [Ambulant treatment of wounds by vacuum sealing].
AB  - The treatment of chronic wounds by vacuum sealing as an outpatient procedure is a
      new method of wound conditioning before closing the defect. The quality of life
      for the patient in his usual surrounding is maintained. Financial aspects also
      play a role in this treatment since costs for the health care system can be
      reduced. Various vacuum pumps, drainages and polymere foams are available and
      suitable for the outpatient treatment. The most important condition is to
      regularly check the vacuum. This can performed by the patient, the relatives or
      nursing staff. The main complication consists in loss of vacuum but technical and
      local or systemic complications can also appear. Individually applied vacuum
      dressings (polyvinyl foam, drainage tube and polymere foil) are practical. The
      ideal pump systems for the outpatient treatment are still not trial.

PMID- 10929656
TI  - [Application of nursing care products in decubitus prevention].
AB  - Pathophysiological factors of decubitus development determine general risk
      situation of individuals. Working principle and used material of common used
      antidecubitus systems can have a strong influence on individual risk potential.
      This study gives an overview about individual advantages and disadvantages in
      working principle, which may be used by different technical devices for decubitus
      prevention.

PMID- 10929657
TI  - [Current aspects of the therapy of chronic wounds].
AB  - The therapy of chronic lesions is a matter of debate among both physicians and
      nursing personnel. Often very different therapeutic approaches are conceivable,
      which contradict each other to some extent, but which must in any case be
      prescribed by a physician who is responsible for them. However, carrying out the
      therapy is often the task of the nursing personnel, who therefore stand in need
      of thorough information concerning the therapeutic considerations in order to
      realize these adequately. Here, important, but all too often neglected aspects of
      therapy are to be described in a summarizing manner.

PMID- 10929658
TI  - Canadian Independent Living Centres: impact on the community.
AB  - There is now widespread interest in developing social policies and practices that
      are grounded in principles of independent living. The Independent Living (IL)
      paradigm reflects a shift in thinking away from traditional approaches to
      supporting persons with disabilities. Independent Living Centres (ILCs), which
      started in the early 1970s in the United States, and in the 1980s in Canada, are
      now a major force in the promotion of the IL concept worldwide. The guiding
      principles of these consumer-driven centres include: promoting an empowerment
      philosophy that incorporates consumer control/self-direction over decision
      making; offering cross-disability support; providing options/choice and
      flexibility; and encouraging inclusion and full participation. Despite their
      prevalence, a surprisingly limited body of research exists on the impact of ILCs.
      A survey was used to investigate the impact of ILCs in Canada on their
      communities of interest (groups connected to the ILCs). Surveys were sent to
      formal organizations, informal groups, and family/friends. A final response rate
      of 52.6% was achieved (111 of 211 surveys returned). Overall, moderate to good
      levels of familiarity, involvement, and impact were found. The results affirmed
      the importance of independent living centres to individual empowerment, community
      change, and the IL movement.

PMID- 10929659
TI  - Parents' and therapists' opinion on features that make a chair useful for a young
      disabled child.
AB  - Children who fail to develop postural skills within a normal time scale are
      prescribed special seating to position them appropriately. For children to derive
      benefit from such seating, they must use it at home as well as in therapy
      sessions. A study was undertaken to explore the opinions of therapists and
      parents concerning the effectiveness and acceptability of a sample of special
      seating available on the UK market for young children. Each of the ten chairs
      selected to represent the range of possible styles and features was tested by 12
      or 16 children in their homes (total sample of 40) for a week each, and four
      therapy centres for a fortnight each. Results obtained from these two populations
      were compared to determine whether chair features considered useful differed when
      used in a therapy centre or family home. Parents' rating for overall usefulness
      was affected by their perception of the child's comfort, as well as the child's
      posture, the level of support the chair offered, and other factors. Therapists'
      response, in contrast, seemed to be mainly influenced by the quality of posture
      children achieved in the chair.

PMID- 10929660
TI  - Collaboration in disability policies--collaboration between stakeholders of
      disability policies in the South and in the North.
AB  - Four studies have been recently undertaken at the Centre for International Child
      Health on the collaboration between the stakeholders of disability policies, in
      Southern and Northern countries. Informed by the literature, the authors have
      explored the roles disabled people's organizations, non-governmental
      organizations, government and professionals play in the design, provision and
      evaluation of services for disabled people. They also highlight the different
      forms participation can take and their most relevant features. The main factors
      influencing collaboration processes are then classified in three different
      categories: social factors, ideology-related factors and project-related factors.
      They are subsequently analysed. The first group encompasses the societal
      framework in which collaboration may take place, while the identity of the
      stakeholders is reflected in the ideology-related factors. The nature of the
      activities undertaken by stakeholders is characterized by the third group of
      factors. In the conclusion it is suggested that stakeholders, and especially
      disabled people's counterparts, should increase their awareness of the social
      model of disability, adopt participatory practices and promote participation at
      higher levels. However, they should acknowledge that it implies more trust
      between partners and an alteration of their structures.

PMID- 10929661
TI  - Health-related quality of life in women at work despite ill-health. A
      prospective, comparative study of hospital cleaners/home-help staff before and
      after staff support.
AB  - The aims of this prospective, non-randomized, comparative study were to elucidate
      how 99 female hospital cleaners and home-helps, at work despite ill-health,
      experienced their quality of life, and to study whether this was affected by a
      particular programme of staff support. The SF-36 questionnaire was used. This
      contains questions on physical, mental and social health status. Health status,
      i.e. experienced health, was assessed by the respondents themselves. Low quality
      of life relating to the dimensions bodily pain, general health perceptions and
      vitality proved to apply both to the hospital cleaners and the home-help staff,
      compared to a normal Swedish female population. No significant differences
      between the intervention group and the reference group were demonstrated among
      either the cleaners or the home-helps. Following the intervention/period of
      customary measures, experienced quality of life was somewhat changed in the
      groups compared with the normal Swedish female population. This may indicate a
      certain unspecific improvement in experienced quality of life in both the
      intervention groups and the reference groups.

PMID- 10929662
TI  - Why employment in integrated settings for people with disabilities?
AB  - This paper reviews the reasons why work in integrated settings for people with
      disabilities is important. Current controversial issues in employment of people
      with disabilities are discussed. These issues are sheltered work versus supported
      employment and natural supports versus the job coach model.

PMID- 10929663
TI  - Athletic competition: a means of improving the self-image of the mentally
      retarded adolescent?
AB  - This study investigated whether participation in athletic training and
      competition positively affects self-perception in the different domains of
      competence in mentally retarded adolescents. We compared the effects of sport
      participation in four groups of eight mentally retarded adolescents over a period
      of 14 months. The adolescents were all students in specialized learning centres.
      The four athletic groups were constituted as follows: segregated basketball
      practice and meets, integrated basketball practice and meets, segregated swimming
      practice and meets, integrated swimming practice and meets. Two other groups
      served as controls: a sedentary group and a group that participated in classic
      adapted physical activities. We used skill tests and Harter's Self-Perception
      Profile for Children (1985) to measure, respectively, athletic skill and domains
      of perceived competence. The results showed that athletic skill increased over
      the 14 months, but the perception of competence in the subjects who participated
      in the segregated meets did not increase significantly in perceived physical
      ability, or in any other domain. Moreover, the integrated basketball group showed
      a decrease in perceived physical ability. The results are discussed in terms of
      the influence of specialized classes.

PMID- 10929664
TI  - Training needs in developing countries: experiences from Lesotho.

PMID- 10929665
TI  - Computer play centres for children with disabilities.
AB  - For all children play is the leading and dominating activity in childhood and
      essential in child development. Many children with severe disabilities have
      limited opportunities to play and need support. Computer play can be a good
      support in habilitation/rehabilitation of children who have not earlier been able
      to play independently. Eight pilot computer play centres were started in Sweden
      in 1992 and since then the number of centres has increased. The target group was
      children with disabilities on the level before reading and writing. This brief
      report is a description of the computer play centres and the first three activity
      years.

PMID- 10929666
TI  - The effects of upper body weight support upon cardiovascular, metabolic and
      electromyographic variables during assisted walking.

PMID- 10929667
TI  - Practical measure for evaluating functional outcomes post hip fracture.

PMID- 10929668
TI  - Test of a communication aid with stored text.

PMID- 10929669
TI  - Nitric oxide and manifestations of lesions of skin and gastrointestinal tract in
      zinc deficiency.
AB  - Information is conflicting as to whether nitric oxide plays a role in the
      pathogenic mechanisms of zinc deficiency. Our series of research using a rat
      model demonstrated that inducible nitric oxide synthase in the intestine is
      upregulated by zinc deficiency when challenged by the injection of IL-1alpha, and
      the systemic administration of nitric oxide synthase inhibitor attenuates both
      intestinal damage and inflammatory skin lesions induced by zinc deficiency.
      Evidence from both transcription and translation levels indicates that inducible
      nitric oxide synthase, one of three nitric oxide synthase isoforms, has already
      been induced in the skin and intestine of zinc-deficient animals, whereas it is
      not generally expressed in normal tissues. On the other hand, total nitric oxide
      synthase activity in the intestine of zinc-deficient animals is significantly
      lower than that in controls, indicating that zinc deficiency may induce a
      potential vulnerability to nitric oxide rather than an absolute increase of
      nitric oxide synthase activities. Tissue zinc and metallothionein levels are
      significantly decreased in zinc-deficient rats, suggesting lowered antioxidative
      capability. Whether nitric oxide is destructive in inflammation may depend on the
      status of homeostasis such as the zinc level of tissues and the balance between
      the three nitric oxide synthase components, although identifying an absolute
      increase of nitric oxide production is of importance. Defining the role of nitric
      oxide provides the rationale for new strategies in zinc deficiency.

PMID- 10929670
TI  - Lipid transporters: membrane transport systems for cholesterol and fatty acids.
AB  - Lipophilic molecules can passively diffuse across cell membranes, a process that
      is driven by the concentration gradient, by availability of acceptors to
      facilitate desorption from the bilayer, and by cellular metabolism. However,
      evidence has accumulated that supports the existence of specialized, protein
      facilitated membrane transport systems for many lipophilic molecules. This has
      generated considerable debate regarding why such systems need to exist. The
      present review summarizes recent developments related to the membrane transport
      systems for cholesterol and fatty acids, which have been shown to involve
      structurally related proteins. General similarities of the cholesterol and fatty
      acid systems to other lipid transport systems (briefly discussed in the
      Introduction section) are highlighted in the Conclusion section. The overall aim
      of the present review is to illustrate why lipid transporters are needed in vivo,
      and how they accomplish specific functions that can not be met by lipid diffusion
      alone.

PMID- 10929672
TI  - Regulation of mammalian iron homeostasis.
AB  - Iron homeostasis is regulated with respect to uptake, storage and utilization.
      Newer work is presented that defines proteins responsible for iron transport,
      sequestration and sensing, and that addresses their regulation at the cellular
      and organismal levels by ambient iron concentrations, demand for erythropoiesis,
      body iron burden, and redox stimuli.

PMID- 10929671
TI  - Structure and function of mammalian sodium-dependent multivitamin transporter.
AB  - This review focuses on the advances made in recent years in the understanding of
      the multivitamin transporter, a unique and important transporter that transports
      not one but three different unrelated water-soluble vitamins namely,
      pantothenate, biotin and lipoate. The transport process mediated by the
      transporter is active and is energized by the transmembrane sodium ion gradient
      as well as the membrane potential. The transporter belongs to the sodium-coupled
      glucose transporter family. The ubiquitous expression of this transporter in
      mammalian tissues and the fact that it is highly conserved across the species
      indicate the nutritional relevance and importance of this transporter.

PMID- 10929673
TI  - Nutritional and insulin regulation of leptin gene expression.
AB  - The leptin and lipogenic enzyme genes contain the common DNA sequences of binding
      sites for Sp1 proteins. These sites appear to be responsible for glucose/insulin
      stimulation and polyunsaturated fatty acid suppression. In rat adipose tissue
      leptin and lipogenic gene expression is similarly regulated by nutritional
      manipulation. Interestingly, leptin has the ability to down-regulate lipogenic
      enzyme expression.

PMID- 10929674
TI  - Measuring body composition: a landmark of quality control for nutritional support
      services.

PMID- 10929675
TI  - Tuberculosis, malnutrition and wasting.
AB  - Malnutrition predisposes to tuberculosis, and tuberculosis causes 'consumption'.
      Starting from current advances and historic findings in epidemiology and
      immunology, we can hope to decipher the effects of macro- and micronutrient
      deficiency upon tuberculosis, the contribution of immune response to the
      pathogenesis of wasting, and the best approach to its treatment.

PMID- 10929676
TI  - Cystic fibrosis: nutritional status and micronutrients.
AB  - Recent studies have focused on the current dietary intake of cystic fibrosis
      patients, the impact of nutritional support on both the nutritional status and
      clinical outcome variables, and the effects on the nutritional status of
      antibiotic therapy and surgical treatment of meconium ileus. In addition to
      weight and height, skinfold measurements, bioelectrical impedance analysis and
      dual energy X-ray absorptiometry have been employed for the determination of
      nutritional status. A proton pump inhibitor has been used successfully along with
      pancreatic enzymes for the improvement of fat absorption. Attention has been paid
      to resting energy expenditure during pulmonary exacerbations, to vitamin K
      function in bone mineralization and to risk factors for low bone mineral density
      in cystic fibrosis. The relationships between glutathione and nutritional status
      have been studied, along with possible interactions with albumin, a potent
      antioxidant. Finally, a beneficial effect of docosahexaenoic acid on cystic
      fibrosis pathology has been suggested, but this requires further critical
      evaluation.

PMID- 10929677
TI  - Current total parenteral nutrition solutions for the neonate are inadequate.
AB  - The amino acid requirements of the parenterally fed neonate are poorly defined.
      Newborn infants are at risk for amino acid deficiency and toxicity, due to lack
      of small intestinal metabolism and metabolic immaturity. We discuss recent
      evidence that identifies inadequacies of commercial amino acid solutions with
      respect to the balance and quantity of aromatic amino acids, and sulphur amino
      acids. We present data demonstrating that impaired small intestinal metabolism
      (or lack of first pass metabolism) alters the whole body requirement for
      methionine, threonine, and arginine, and discuss the potential adverse effects of
      excess or inadequate parenteral amino acid intake.

PMID- 10929678
TI  - Nutrition in Crohn's disease.
AB  - Nutrition plays an important role in Crohn's disease. This review provides
      further insights into the relationship between nutrition and Crohn's disease and
      focuses on three different aspects: dietary aetiological factors, nutritional
      status and nutritional therapy in Crohn's disease.

PMID- 10929679
TI  - Are oral nutritional supplements of benefit to patients in the community?
      Findings from a systematic review.
AB  - Although the use of oral nutritional supplements has increased in the community
      setting, no consensus exists about the benefits of their use in patients with
      different diseases and conditions. This article highlights new findings from a
      critical, systematic review of 84 trials, which has led to a rationale for the
      use of supplements in patients with chronic conditions in the community and has
      identified key areas for future research.

PMID- 10929680
TI  - Dynamic assessment of fat-free mass during catabolism and recovery.
AB  - Catabolism of fat-free mass affects both the quality of life and survival of
      patients. Because of variations in fluid status during acute illness, changes in
      body weight are difficult to evaluate and interpret during treatment. Nutritional
      assessment should therefore evaluate fat-free and fat mass changes during
      metabolic stress and catabolism. We have chosen to discuss bioelectrical
      impedance analysis, including the various bioelectrical impedance analysis
      techniques (i.e. multi-frequency and bioimpedance spectroscopy), as an easy, non
      invasive, portable bedside technique that is operator-independent for evaluating
      fat-free and fat mass compartments and their changes during treatment. Clinical
      examples of the determination of fat-free mass in healthy and ill individuals are
      also presented.

PMID- 10929682
TI  - Bibliography. Current world literature. Nutrition in wasting diseases.

PMID- 10929681
TI  - Bibliography. Current world literature. Genes and nutrition.

PMID- 10929684
TI  - Strategies for ascertaining ovarian reserve among women suspected of
      subfertility.
AB  - "Ovarian reserve" describes the native oocyte endowment and is closely associated
      with reproductive potential. As a diagnostic entity, ovarian reserve screening
      developed from clinical experience with the advanced reproductive technologies-
      particularly in vitro fertilization. Diminished ovarian reserve generally
      presages a poor response to any fertility treatment, and sharply limits the
      possibility of successful pregnancy. Screening for ovarian reserve is a
      fundamental component of the initial infertility evaluation, since it is a key
      determinant of what, if any, treatment should be offered. Methods of clinical
      ascertainment of ovarian reserve may be classified in two groups: passive and
      provocative testing. Both approaches seek to provide information regarding oocyte
      quality and quantity, which then may be used to direct specific therapeutic
      interventions. This monograph presents basic elements of ovarian reserve testing
      as currently practiced, and provides insights into the interpretation and
      limitations of these assessments.

PMID- 10929683
TI  - Multiple gestation: reflections on epidemiology, causes, and consequences.
AB  - Multiple births (of all orders) increased in epidemic proportions in the years
      1971-1997. Twins increased 53%, 32%, 31%, and 83% in white, Afro-American, Native
      American and Mexican American women, respectively. Triplet, quadruplet, and
      quintuplet+ births increased >400%, >1,100%, and >500%, respectively, in the same
      years. The principal causes of these changes are related to the increasing age of
      the maternal cohort and an increasing incidence of fertility-inhibiting diseases
      and conditions in association with advancing maternal age. Major immediate
      consequences of these changes include disproportionately large numbers of infants
      born at <33 weeks' gestation (1.7% for singletons vs. 41.2% for triplets) and at
      <1,500 g birth weight (1.1% for singletons vs. 31.9% for triplets). Additional
      short-term consequences include an almost 2,000% increase in infant deaths (per
      1,000 live births) among triplets compared with singletons (190.4 vs. 11.2). Long
      term risks include a 300% increase in the relative risk of handicap in triplets
      compared with singletons (2.9 vs. 1.0), and a 650% increase in the rate of
      cerebral palsy per 1,000 live births in triplets compared with singletons (26.6
      vs. 1.6). Peripartum costs relate to prematurity rather than plurality, as do
      lifetime survivorship costs, which relate to morbidities and subsequent health
      related problems.

PMID- 10929685
TI  - Influence of weight and body fat distribution on bone density in postmenopausal
      women.
AB  - OBJECTIVE: To determine whether obesity or body fat distribution induces a
      greater modification on bone remodeling biochemistry (BRB) and bone density in
      postmenopausal women. METHODS: One hundred and thirteen postmenopausal patients
      were studied. They were initially divided according to body mass index (BMI), and
      afterwards by waist-hip ratio (WHR) as well as combinations of the two factors.
      Hormone measurements and assessments of BRB were also done. Dual-emission X-ray
      absorptiometry from the lumbar column and hip was performed with Lunar DPXL
      equipment, and the standard deviation in relation to young adult (T) and age
      matched subjects (Z) was calculated. Statistical analysis was done by the Mann
      Whitney U test. The relation of BMI and WHR with the variables was calculated by
      simple regression analysis. RESULTS: When divided according to BMI, there was
      greater bone density in the femoral neck in those with normal weight. After
      dividing according to WHR, the Z scores had a trend to a lesser decrease in those
      with upper level body fat distribution. Divided according to BMI and WHR, obese
      patients with upper-level body fat distribution had greater bone density in the
      lumbar column than those with normal weight and lower-level body fat
      distribution. With the same WHR, those with normal weight had greater bone
      density than those who were obese. CONCLUSIONS: A beneficial effect of upper
      level body fat distribution on bone density was found. It is greater than that
      from obesity alone, and obesity and upper-level body fat distribution have an
      additive effect on bone density.

PMID- 10929686
TI  - The need for clinical evaluation and semen analysis of infertile men.
AB  - OBJECTIVE: Although many men in Third World countries are reluctant to
      participate in an infertility work-up, we collected data from a group of husbands
      of females attending our infertility clinic. We intend to present these results
      as motivation for other men to realize the importance of an evaluation when they
      are involved in a barren marriage. STUDY METHODS: A detailed history was taken,
      and physical and urogenital examination was carried out on 400 male partners of
      women attending the infertility clinic of PGIMER Chandigarh. Semen analysis was
      interpreted as normal or abnormal according to the WHO manual. RESULTS: Age of
      the male partners of 400 infertile couples and their duration of infertility
      correlated with the pregnancy rate. Fifty percent of the men with a past history
      of infection, medical or surgical problems had abnormal semen analysis. The
      presence of urogenital abnormalities had a significant correlation with low sperm
      count and low motility. Social problems related to alcohol and smoking produced
      low pregnancy rates. CONCLUSION: A detailed history, examination and work-up of
      male partners of infertility couples is as important as in the female partner.
      Counseling and treatment may improve pregnancy rates.

PMID- 10929687
TI  - L-carnitine levels in the seminal plasma of fertile and infertile men:
      correlation with sperm quality.
AB  - OBJECTIVE: To confirm the presence of L-carnitine in human seminal plasma, to
      show differences between L-carnitine concentrations in fertile and infertile
      subjects, and to show potential relationships between L-carnitine and semen
      quality. STUDY DESIGN: Seminal plasma from 101 men obtained by masturbation was
      examined for the presence of L-carnitine. Semen samples were divided as follows:
      (a) in eight groups according to the etiology of fertility, (b) in two groups on
      the basis of normal or abnormal spermiogram, (c) correlation of the amount of L
      carnitine in seminal plasma with values of the spermiogram. RESULTS: We found the
      following: (1) L-carnitine levels differ significantly between controls and the
      patient groups (P < .0001) (2) The group with normal spermiogram has a mean value
      for L-carnitine of 478.4 while the abnormal one comes to 100.58. This difference
      is statistically significant (P < .0001). (3) There is a statistically
      significant, positive correlation between L-carnitine and the number of
      spermatozoa, the percentage of motile spermatozoa, and the percentage of normal
      forms (P < .0001). CONCLUSION: These findings suggest that determination of
      seminal carnitine values might provide the physician with an additional means of
      evaluating the infertile male.

PMID- 10929688
TI  - Noncontraceptive benefits of oral contraceptive use: an evidence-based approach.
AB  - Numerous noncontraceptive benefits of oral contraceptive (OC) use have been
      identified. These include a reduction in ovarian and endometrial cancers,
      functional ovarian cysts, pelvic inflammatory disease, benign breast disease,
      iron-deficiency, menstrual disorders, dysmenorrhea, bone loss, and acne. The best
      "evidence" is in the area of cancer prevention, maintenance of bone mineral
      density (BMD) and the treatment of acne vulgaris. Based on the body of evidence
      available today, several evidence-based clinical recommendations can be made
      regarding BMD. In young, reproductive-age women with a hypoestrogenic condition,
      there is a protective effect on BMD with OC use. In older reproductive-age women
      with declining ovarian function, there is also a protective effect on BMD with OC
      use. With long-term use of OCs (greater than 5 years) protection increases with
      increasing duration of use. There is a high degree of biologic plausibility for
      the beneficial effect of OC use on states associated with androgen excess, such
      as acne. Two randomized, placebo-controlled, multicenter clinical trials of a
      triphasic norgestimate-containing OC were published. Using evidence-based
      criteria, there is strong evidence that this OC effectively treats acne vulgaris.
      As further experimental and observational studies are completed, they should
      substantiate many of the other known benefits; thus, further evidence-based
      recommendations will be possible.

PMID- 10929689
TI  - Psychometric testing of fatigue instruments for use with cancer patients.
AB  - BACKGROUND: Cancer treatment-related fatigue (CRF) is a common side effect of
      cancer treatment. A problem identified in most reviews of CRF is lack of sound
      approaches to measurement that are congruent with the conceptualization of CRF as
      a self-perceived state. The diversity of instruments available to measure fatigue
      and the lack of comprehensive testing of several promising instruments with
      cancer patients undergoing treatment provided the rationale for this study. The
      purpose of this article is to report the results of psychometric testing of
      several fatigue instruments in patients undergoing cancer treatment. OBJECTIVES:
      The aims of this study were to determine the reliability, validity, and
      responsiveness of each instrument and to determine the ability of each instrument
      to capture CRF. METHODS: Existing fatigue instruments with published psychometric
      information that indicated suitability for further testing were selected and
      included the Profile of Mood States Short Form fatigue subscale (F_POMS-sf),
      Multidimensional Assessment of Fatigue (MAF), Lee Fatigue Scale (LFS), and the
      Multidimensional Fatigue Inventory (MFI). Data were collected at a university
      based clinical cancer center and a freestanding comprehensive cancer center.
      Subjects completed all study instruments, which were presented in random order,
      at a time when CRF was expected to be high and again when it was expected to be
      low. A subset of subjects completed the instruments within 48 hours of one of the
      data collection points when CRF was expected to be relatively unchanged to
      provide stability data. RESULTS: Reliability estimates using Cronbach's alpha
      indicated that all instruments examined had good internal consistency. Test
      retest correlations showed good stability for total scores on all the
      instruments, but some subscales of the LFS and MFI had marginal stability. Factor
      analysis of all instruments indicated that only the LFS and the F_POMS-sf fully
      supported their construct validity. All of the instruments showed responsiveness
      to changes in CRF related to treatment. CONCLUSIONS: The results of the study
      provide researchers and clinicians with detailed comparisons of the performance
      of established fatigue measures in cancer patients undergoing treatment to use
      when selecting measures of CRF.

PMID- 10929690
TI  - The impact of nurses' empathic responses on patients' pain management in acute
      care.
AB  - BACKGROUND: Although nurses have the major responsibility for pain management,
      little is known about nurses' responses to patients in the process of managing
      acute pain. OBJECTIVE: To examine the relationship between nurses' empathic
      responses and their patients' pain intensity and analgesic administration after
      surgery. METHODS: Two hundred twenty-five patients from four cardiovascular units
      in three university-affiliated hospitals were interviewed on the third day after
      their initial, uncomplicated coronary artery bypass graft (CABG) surgery about
      their pain and current pain management. Concurrently, their nurses' (n = 94)
      empathy and pain knowledge and beliefs were assessed. Patient data were
      aggregated and linked with the assigned nurse to form 80 nurse-patient pairs.
      RESULTS: Nurses were moderately empathic, and their responses did not
      significantly influence their patients' pain intensity or analgesia administered.
      Patients reported moderate to severe pain but received only 47% of their
      prescribed analgesia. Patients' perceptions of their nurse's attention to their
      pain were not positive, and empathy explained only 3% of variance in patients'
      pain intensity. Deficits in knowledge and misbeliefs about pain management were
      evident for nurses independent of empathy, and knowledge explained 7% of variance
      in analgesia administered. Hospital sites varied significantly in analgesic
      practices and pain inservice education for nurses. CONCLUSIONS: Empathy was not
      associated with patients' pain intensity or analgesic administration.

PMID- 10929691
TI  - Negative thinking mediates the effect of self-esteem on depressive symptoms in
      college women.
AB  - BACKGROUND: One of every three women between 18 and 24 years of age may be
      significantly depressed. Younger women have shown increasing rates of unipolar
      depression since the 1950s, and the average age of onset continues to decline.
      OBJECTIVES: To examine the prevalence and correlates of high depressive symptoms
      in single college women 18 to 24 years of age. Negative thinking was posited to
      mediate the relationship between self-esteem and depressive symptoms. METHODS: A
      sample of 246 women was recruited from a university student body. Each woman
      completed a survey that included the Center for Epidemiologic Studies-Depression
      Scale, the Beck Depression Inventory, the Rosenberg Self-esteem Scale, the
      Crandell Cognitions Inventory, and the Automatic Thoughts Questionnaire. RESULTS:
      Of the women, 35% had high depressive symptoms. Negative thinking mediated the
      relationship between self-esteem and depressive symptoms. However, self-esteem
      also showed a weak direct effect on depressive symptoms. CONCLUSION: The findings
      suggest that negative thinking may play an important role in the development of
      depressive symptoms in college women.

PMID- 10929692
TI  - A social cognitive-based model for condom use among college students.
AB  - BACKGROUND: Social cognitive theory has been used extensively to explain health
      behaviors. Although the influence of one construct in this model-self-efficacy
      has been well established, the role of other social cognitive constructs has not
      received as much attention in human immunodeficiency virus (HIV) prevention
      research. More complete understanding of how social cognitive constructs operate
      together to explain condom use behaviors would be useful in developing HIV and
      sexually transmitted disease (STD) prevention programs for college students.
      OBJECTIVE: The primary aim of this study was to test a social cognitive-based
      model of condom use behaviors among college students. METHODS: Data were
      collected from a sample of college students attending six different colleges and
      universities. Participants were 18 to 25 years of age, single, and sexually
      active. For the sample of 1,380 participants, the mean age was 20.6 years (SD =
      1.76). Most participants reported having had vaginal intercourse (95.8%) and oral
      sex (86.5%); 16% reported anal sex. FINDINGS: Self-efficacy was related directly
      to condom use behaviors and indirectly through its effect on outcome
      expectancies. As predicted, self-efficacy was related to anxiety, but anxiety was
      not related to condom use. Substance use during sexual encounters was related to
      outcome expectancies but not to condom use as predicted. CONCLUSIONS: Overall,
      the findings lend support to a condom use model based on social cognitive theory
      and provide implications for HIV interventions. Interventions that focus on self
      efficacy are more likely to reduce anxiety related to condom use, increase
      positive perceptions about condoms, and increase the likelihood of adopting
      condom use behaviors.

PMID- 10929693
TI  - The impact of two transfer techniques used during skin-to-skin care on the
      physiologic and behavioral responses of preterm infants.
AB  - BACKGROUND: Conservation of energy assumes an important role in the care of
      infants requiring assisted ventilation, yet little research has been conducted on
      this group of infants in terms of thermoregulation, oxygenation, heart rate, or
      sleep states during skin-to-skin care. OBJECTIVES: To compare the impact of two
      different transfer techniques used in skin-to-skin care (nurse transfer and
      parent transfer) on physiologic stability and other descriptive measures of
      physiologic stability related to energy conservation in ventilated preterm
      infants during and after skin-to-skin care. METHOD: Fifteen ventilated preterm
      infants weighing a mean of 1,094 g were randomly assigned to receive either
      parent or nurse-to-parent transfer on the first of 2 consecutive days and the
      alternate method the following day. Temperature was taken before and after skin
      to-skin care. Oxygen saturation and heart rate were recorded minute by minute,
      and the Assessment of Behavioral Systems Observation (ABSO) scale scores was used
      to measure physiologic organization, motor organization, self-regulation, and
      need for caregiver facilitation during transfer to and from the parent and during
      pre, post, and skin-to-skin periods. RESULTS: Temperature remained stable. Oxygen
      saturation decreased and heart rate increased when the infant was transferred to
      and from the parent, but returned to baseline levels during and after skin-to
      skin care regardless of the transfer method. Infants showed more physiologic and
      motor disorganization, less self-regulation, and more need for caregiver
      facilitation during transfers to and from the parent than during the pre, post,
      and skin-to-skin care periods. CONCLUSIONS: Both transfer methods resulted in
      physiologic disorganization. However, during and after skin-to-skin care, infants
      exhibited no signs of energy depletion.

PMID- 10929694
TI  - Communication of research and practice knowledge in nursing literature.
AB  - BACKGROUND: Previous research did not indicate whether communication occurred
      between the research and practice components of nursing knowledge. OBJECTIVES:
      This study was designed to examine the extent of communication between or within
      the nursing-research and nursing-practice components of the nursing literature.
      METHODS: Specific citing/cited relationships from the Current Index to Nursing
      and Allied Health Literature (CINAHL) are analyzed using citation analysis. The
      sample was taken from the population of indexed documents that contained
      references, that had the subject code of nursing, and that were originally
      published in the United States or Canada in 1989. RESULTS: The results show that
      authors of research articles tend to cite research articles more often than
      practice articles, and that authors of practice articles tend to cite practice
      articles more often than research articles. Authors with research degrees publish
      research articles more often than would be expected by chance, and authors with
      clinical and undergraduate degrees publish practice articles more often than
      expected. Authors associated with research institutions tend to publish research
      articles, and those affiliated with service institutions tend to publish practice
      articles. Most cited documents (69.4%) are from disciplines other than nursing.
      CONCLUSIONS: The existence of communication between the research and the practice
      component of nursing knowledge was demonstrated and appears to be more prevalent
      than previously indicated. Further research on how the cited literature is used
      would enable us to know about the depth and quality of the communication event
      and to note variations as the body of nursing knowledge evolves.

PMID- 10929695
TI  - Maintaining study validity in a changing clinical environment.
AB  - BACKGROUND: Nurse scientists who conduct intervention research in a variety of
      clinical settings find themselves facing numerous challenges posed by today's
      changing and sometimes complex health care environment. Maintaining study
      validity thus becomes a major focus of interventional research, but existing
      literature does not fully address challenges to study validity nor offer
      potential solutions. OBJECTIVES: The purposes of this paper are to 1) discuss
      methodologic challenges to maintaining study validity of intervention research
      that is conducted in a changing clinical environment, and 2) share strategies for
      maximizing study validity. METHODS: A recently completed intervention study is
      used as an example to discuss two specific areas that affected study validity,
      provide examples of selected threats to validity, and outline strategies used to
      minimize these threats. RESULTS: Careful definition of goals, thoughtful decision
      making, and implementation of specific strategies to maintain study validity
      helped increased the rigor of the research. CONCLUSIONS: Investigators conducting
      intervention research in changing clinical settings can reduce threats to study
      validity and increase design rigor by considering clinical realities (e.g.,
      clinician-researcher role conflict) when making methodologic decisions, becoming
      familiar with the setting, and involving clinicians in the research.

PMID- 10929696
TI  - Creation and analysis of a computerized database of interventions to facilitate
      adult sleep.
AB  - BACKGROUND: Although sleep problems are a frequent complaint of ill and older
      adults, there is no ready source of continually updated scientific knowledge
      about sleep promotion interventions used by nurses. OBJECTIVES: To create a
      database of sleep promotion research and to describe the nature and strength of
      studies about nursing interventions used to promote sleep in adults. METHODS:
      Computer, hand, ancestry, and author searches were used to identify nursing and
      related-discipline studies of sleep promotion in adults. An experimental software
      program, arcs, was used to store, retrieve, examine, and summarize sleep research
      findings. RESULTS: Twelve interventions within the basic scope of nursing
      practice were identified. All were nonpharmacologic. Interventions were grouped
      according to their presumed mechanism of action: 1) to relax the sleeper, 2) to
      manage noise, 3) to re-pattern the sleep-wake schedule, or 4) to inform the
      sleeper about sleep hygiene. CONCLUSIONS: The research base underpinning sleep
      promotion practices in nursing is sparse. The use of relaxation approaches to
      promote sleep in those with chronic insomnia has the most support. Extensive
      research involving other interventions and populations is needed. As more studies
      become available, they can be added to the computer database, thus facilitating
      dissemination of scientific knowledge to guide nursing practice.

PMID- 10929697
TI  - PRE-OPportunity knocks: a different way to think about the preoperative
      evaluation.

PMID- 10929698
TI  - Revealing a medication error.

PMID- 10929699
TI  - Miglitol and hepatotoxicity in type 2 diabetes mellitus.

PMID- 10929700
TI  - Early detection and treatment of skin cancer.
AB  - The incidence of skin cancer is increasing by epidemic proportions. Basal cell
      cancer remains the most common skin neoplasm, and simple excision is generally
      curative. Squamous cell cancers may be preceded by actinic keratoses-premalignant
      lesions that are treated with cryotherapy, excision, curettage or topical 5
      fluorouracil. While squamous cell carcinoma is usually easily cured with local
      excision, it may invade deeper structures and metastasize. Aggressive local
      growth and metastasis are common features of malignant melanoma, which accounts
      for 75 percent of all deaths associated with skin cancer. Early detection greatly
      improves the prognosis of patients with malignant melanoma. The differential
      diagnosis of pigmented lesions is challenging, although the ABCD and seven-point
      checklists are helpful in determining which pigmented lesions require excision.
      Sun exposure remains the most important risk factor for all skin neoplasms. Thus,
      patients should be taught basic "safe sun" measures: sun avoidance during peak
      ultraviolet-B hours; proper use of sunscreen and protective clothing; and
      avoidance of suntanning.

PMID- 10929701
TI  - Preoperative evaluation.
AB  - A history and physical examination, focusing on risk factors for cardiac,
      pulmonary and infectious complications, and a determination of a patient's
      functional capacity, are essential to any preoperative evaluation. In addition,
      the type of surgery influences the overall perioperative risk and the need for
      further cardiac evaluation. Routine laboratory studies are rarely helpful except
      to monitor known disease states. Patients with good functional capacity do not
      require preoperative cardiac stress testing in most surgical cases. Unstable
      angina, myocardial infarction within six weeks and aortic or peripheral vascular
      surgery place a patient into a high-risk category for perioperative cardiac
      complications. Patients with respiratory disease may benefit from perioperative
      use of bronchodilators or steroids. Patients at increased risk of pulmonary
      complications should receive instruction in deep-breathing exercises or incentive
      spirometry. Assessment of nutritional status should be performed. An albumin
      level of less than 3.2 mg per dL (32 g per L) suggests an increased risk of
      complications. Patients deemed at risk because of compromised nutritional status
      may benefit from pre- and postoperative nutritional supplementation.

PMID- 10929702
TI  - Postobstructive pulmonary edema.
AB  - Pulmonary edema is a potentially life-threatening complication of acute airway
      obstruction. It develops rapidly, without warning, in persons who are otherwise
      well. Two forms of postobstructive pulmonary edema (POPE) have been identified.
      POPE I follows sudden, severe upper airway obstruction. POPE II occurs following
      surgical relief of chronic upper airway obstruction. Treatment for both is
      supportive. Full and rapid recovery can be expected with appropriate management.

PMID- 10929703
TI  - Update on digoxin therapy in congestive heart failure.
AB  - Congestive heart failure is a progressive disease with significant morbidity and
      mortality. Despite advances in the prevention and treatment of cardiovascular
      diseases, the incidence and prevalence of congestive heart failure have increased
      in recent years. Contributing factors include increased survival in patients with
      coronary artery disease (especially myocardial infarction), an aging population
      and significant advances in the control of other potentially lethal diseases. New
      and existing agents, including angiotensin-converting enzyme inhibitors, beta
      blockers and, more recently, spironolactone, are being used increasingly to
      prolong life in patients with heart failure. Although digoxin has been used to
      treat heart failure for more than 200 years, its role in patients with congestive
      heart failure and sinus rhythm is still debatable. Over the past decade, digoxin
      has received renewed attention because of recognition of its neurohormonal effect
      and the successful use of lower dosages. In recent trials, digoxin has been shown
      to reduce morbidity associated with congestive heart failure but to have no
      demonstrable effect on survival. The goal of digoxin therapy in patients with
      congestive heart failure is to improve quality of life by reducing symptoms and
      preventing hospitalizations.

PMID- 10929704
TI  - Medical management of obesity.
AB  - Obesity is one of the most common medical problems in the United States and a
      risk factor for illnesses such as hypertension, diabetes, degenerative arthritis
      and myocardial infarction. It is a cause of significant morbidity and mortality
      and generates great social and financial costs. Obesity is defined as a body mass
      index greater than 30. Many patients accomplish weight loss with diet, exercise
      and lifestyle modification. Others require more aggressive therapy. Weight loss
      medications may be appropriate for use in selected patients who meet the
      definition of obesity or who are overweight with comorbid conditions. Medications
      are formulated to reduce energy intake, increase energy output or decrease the
      absorption of nutrients. Drugs cannot replace diet, exercise and lifestyle
      modification, which remain the cornerstones of obesity treatment. Two new agents,
      sibutramine and orlistat, exhibit novel mechanisms of action and avoid some of
      the side effects that occurred with earlier drugs. Sibutramine acts to block
      uptake of serotonin, norepinephrine and dopamine, while orlistat decreases fat
      absorption in the intestines.

PMID- 10929705
TI  - ACOG develops guidelines for induction of labor.

PMID- 10929706
TI  - Apoptotic pathways: paper wraps stone blunts scissors.

PMID- 10929707
TI  - Many paths to the top of the mountain: diverse evolutionary solutions to
      centromere structure.

PMID- 10929708
TI  - Biomedical discovery with DNA arrays.

PMID- 10929709
TI  - Myf-5 revisited: loss of early myotome formation does not lead to a rib phenotype
      in homozygous Myf-5 mutant mice.

PMID- 10929710
TI  - A mechanism for coupling exit from mitosis to partitioning of the nucleus.
AB  - Exit from mitosis must not occur prior to partitioning of chromosomes between
      daughter cells. We find that the GTP binding protein Tem1, a regulator of mitotic
      exit, is present on the spindle pole body that migrates into the bud during S
      phase and mitosis. Tem1's exchange factor, Lte1, localizes to the bud. Thus, Tem1
      and Lte1 are present in the same cellular compartment (the bud) only after the
      nucleus enters the bud during nuclear division. We also find that the presence of
      Tem1 and Lte1 in the bud is required for mitotic exit. Our results suggest that
      the spatial segregation of Tem1 and Lte1 ensures that exit from mitosis only
      occurs after the genetic material is partitioned between mother and daughter
      cell.

PMID- 10929711
TI  - Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase
      activation by eliminating IAP inhibition.
AB  - We report here the identification of a novel protein, Smac, which promotes
      caspase activation in the cytochrome c/Apaf-1/caspase-9 pathway. Smac promotes
      caspase-9 activation by binding to inhibitor of apoptosis proteins, IAPs, and
      removing their inhibitory activity. Smac is normally a mitochondrial protein but
      is released into the cytosol when cells undergo apoptosis. Mitochondrial import
      and cleavage of its signal peptide are required for Smac to gain its apoptotic
      activity. Overexpression of Smac increases cells' sensitivity to apoptotic
      stimuli. Smac is the second mitochondrial protein, along with cytochrome c, that
      promotes apoptosis by activating caspases.

PMID- 10929712
TI  - Identification of DIABLO, a mammalian protein that promotes apoptosis by binding
      to and antagonizing IAP proteins.
AB  - To identify proteins that bind mammalian IAP homolog A (MIHA, also known as
      XIAP), we used coimmuno-precipitation and 2D immobilized pH gradient/SDS PAGE,
      followed by electrospray ionization tandem mass spectrometry. DIABLO (direct IAP
      binding protein with low pI) is a novel protein that can bind MIHA and can also
      interact with MIHB and MIHC and the baculoviral IAP, OpIAP. The N-terminally
      processed, IAP-interacting form of DIABLO is concentrated in membrane fractions
      in healthy cells but released into the MIHA-containing cytosolic fractions upon
      UV irradiation. As transfection of cells with DIABLO was able to counter the
      protection afforded by MIHA against UV irradiation, DIABLO may promote apoptosis
      by binding to IAPs and preventing them from inhibiting caspases.

PMID- 10929713
TI  - Distinct initiation and maintenance mechanisms cooperate to induce G1 cell cycle
      arrest in response to DNA damage.
AB  - DNA damage causes stabilization of p53, leading to G1 arrest through induction of
      p21cip1. As this process requires transcription, several hours are needed to
      exert this response. We show that DNA damage causes an immediate and p53
      independent G1 arrest, caused by rapid proteolysis of cyclin D1. Degradation is
      mediated through a previously unrecognized destruction box in cyclin D1 and leads
      to a release of p21cip1 from CDK4 to inhibit CDK2. Interference with cyclin D1
      degradation prevents initiation of G1 arrest and renders cells more susceptible
      to DNA damage, indicating that cyclin D1 degradation is an essential component of
      the cellular response to genotoxic stress. Thus, induction of G1 arrest in
      response to DNA damage is minimally a two step process: a fast p53-independent
      initiation of G1 arrest mediated by cyclin D1 proteolysis and a slower
      maintenance of arrest resulting from increased p53 stability.

PMID- 10929714
TI  - Cell cycle-regulated modification of the ribosome by a variant multiubiquitin
      chain.
AB  - Ubiquitin is ligated to L28, a component of the large ribosomal subunit, to form
      the most abundant ubiquitin-protein conjugate in S. cerevisiae. The human
      ortholog of L28 is also ubiquitinated, indicating that this modification is
      highly conserved in evolution. During S phase of the yeast cell cycle, L28 is
      strongly ubiquitinated, while reduced levels of L28 ubiquitination are observed
      in G1 cells. L28 ubiquitination is inhibited by a Lys63 to Arg substitution in
      ubiquitin, indicating that L28 is modified by a variant, Lys63-linked
      multiubiquitin chain. The K63R mutant of ubiquitin displays defects in ribosomal
      function in vivo and in vitro, including a dramatic sensitivity to translational
      inhibitors. L28, like other ribosomal proteins, is metabolically stable.
      Therefore, these data suggest a regulatory role for multiubiquitin chains that is
      reversible and does not function to target the acceptor protein for degradation.

PMID- 10929715
TI  - Topographic mapping from the retina to the midbrain is controlled by relative but
      not absolute levels of EphA receptor signaling.
AB  - Topographic maps are a fundamental feature of sensory representations in nervous
      systems. The formation of one such map, defined by the connection of ganglion
      cells in the retina to their targets in the superior colliculus of the midbrain,
      is thought to depend upon an interaction between complementary gradients of
      retinal EphA receptors and collicular ephrin-A ligands. We have tested this
      hypothesis by using gene targeting to elevate EphA receptor expression in a
      subset of mouse ganglion cells, thereby producing two intermingled ganglion cell
      populations that express distinct EphA receptor gradients. We find that these two
      populations form separate maps in the colliculus, which can be predicted as a
      function of the net EphA receptor level that a given ganglion cell expresses
      relative to its neighbors.

PMID- 10929716
TI  - Congenital deafness and sinoatrial node dysfunction in mice lacking class D L
      type Ca2+ channels.
AB  - Voltage-gated L-type Ca2+ channels (LTCCs) containing a pore-forming alpha1D
      subunit (D-LTCCs) are expressed in neurons and neuroendocrine cells. Their
      relative contribution to total L-type Ca2+ currents and their physiological role
      and significance as a drug target remain unknown. Therefore, we generated D-LTCC
      deficient mice (alpha1D-/-) that were viable with no major disturbances of
      glucose metabolism. alpha1D-/-mice were deaf due to the complete absence of L
      type currents in cochlear inner hair cells and degeneration of outer and inner
      hair cells. In wild-type controls, D-LTCC-mediated currents showed low activation
      thresholds and slow inactivation kinetics. Electrocardiogram recordings revealed
      sinoatrial node dysfunction (bradycardia and arrhythmia) in alpha1D-/- mice. We
      conclude that alpha1D can form LTCCs with negative activation thresholds
      essential for normal auditory function and control of cardiac pacemaker activity.

PMID- 10929717
TI  - Structural basis for the interaction between FxFG nucleoporin repeats and
      importin-beta in nuclear trafficking.
AB  - We describe the crystal structure of a complex between importin-beta residues 1
      442 (Ib442) and five FxFG nucleoporin repeats from Nsp1p. Nucleoporin FxFG cores
      bind on the convex face of Ib442 to a primary site between the A helices of HEAT
      repeats 5 and 6, and to a secondary site between HEAT repeats 6 and 7. Mutations
      at importin-beta Ile178 in the primary FxFG binding site reduce both binding and
      nuclear protein import, providing direct evidence for the functional significance
      of the importin-beta-FxFG interaction. The FxFG binding sites on importin-beta do
      not overlap with the RanGTP binding site. Instead, RanGTP may release importin
      beta from FxFG nucleoporins by generating a conformational change that alters the
      structure of the FxFG binding site.

PMID- 10929718
TI  - Functional discovery via a compendium of expression profiles.
AB  - Ascertaining the impact of uncharacterized perturbations on the cell is a
      fundamental problem in biology. Here, we describe how a single assay can be used
      to monitor hundreds of different cellular functions simultaneously. We
      constructed a reference database or "compendium" of expression profiles
      corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae,
      and we show that the cellular pathways affected can be determined by pattern
      matching, even among very subtle profiles. The utility of this approach is
      validated by examining profiles caused by deletions of uncharacterized genes: we
      identify and experimentally confirm that eight uncharacterized open reading
      frames encode proteins required for sterol metabolism, cell wall function,
      mitochondrial respiration, or protein synthesis. We also show that the compendium
      can be used to characterize pharmacological perturbations by identifying a novel
      target of the commonly used drug dyclonine.

PMID- 10929719
TI  - Combined management of intracranial aneurysms by surgical and endovascular
      treatment. Modalities and results from a series of 395 cases.
AB  - The selective occlusion of saccular intracranial aneurysms may be achieved by two
      techniques: microsurgical clipping and endovascular coiling. Each of them have
      particular indications which need to be defined. We report on a series in which
      both techniques were applied. From September 1992 to June 1996, 395 consecutive
      patients with small or large aneurysm were treated either by surgery (N = 102) or
      by endovascular coiling (N = 293). Coiling was chosen each time the shape of the
      aneurysm seemed to be appropriate for this treatment: narrow neck and ratio neck
      diameter by sac diameter less than one third. Satisfactory results with complete
      or subtotal obliteration and no recanalization on the following controls at 1, 6,
      12 and 36 months, were obtained in 92% before retreatment and in 98.8% after
      retreatment. Unsatisfactory results were observed after surgery in 7 cases and in
      25 cases after embolization. After retreatment, it remains 3 post-surgical and 2
      post-endovascular cases. In the overall series, good and excellent clinical
      outcome was noted in 90% for small aneurysms and in 86.5% for large ones;
      mortality was of 4.8%. In a series in which were applied both types of treatment,
      surgery in 25% and endovascular technique in 75%, good results in terms of
      aneurysm occlusion and clinical results were achieved. These results are as good
      as the best series in which surgery was the only choice. Therefore with
      appropriate selection, endovascular treatment is a good alternative for treatment
      of the majority of saccular aneurysms.

PMID- 10929720
TI  - Dissection from fundus to neck for ruptured anterior and middle cerebral artery
      aneurysms at the acute surgery.
AB  - It is generally believed that a ruptured aneurysm should be dissected from its
      neck to its fundus or that only the neck should be dissected. This study was
      conducted to clarify whether, during the acute stage, intra-operative bleeding
      occurs at the same site as the initial rupture point when aneurysms are dissected
      completely without clipping. The subjects were 170 patients with ruptured
      anterior or middle cerebral artery aneurysms who were surgically treated by day
      7. These aneurysms were operated on through an interhemispheric or a pterional
      route, respectively. Most of the aneurysms were dissected from the fundus to the
      neck. Complete exposure of entire aneurysms without temporary clipping was
      performed in 118 of 170 patients (69%). Intra-operative aneurysmal rupture
      occurred during 16 (9%) operative procedures. There were no significant
      correlations between the rate of intra-operative aneurysmal rupture occurrence
      and the timing of the operation, pre-operative grade or location of ruptured
      aneurysms. Intra-operative aneurysmal rupture occurred during dissection of the
      aneurysm itself in 8 patients, during dissection of the artery adhering to the
      aneurysm in 5 and during clip application in 3. In all the patients whose
      aneurysms ruptured during aneurysmal dissection, the rupture was caused by injury
      to the aneurysm and was not directly related to complete exposure of the
      aneurysm. Intra-operative bleeding did not occur at the same site as the initial
      rupture point even when the entire aneurysmal complex was dissected from the
      fundus to the neck without clipping.

PMID- 10929721
TI  - Long-term functional effects of aneurysmal subarachnoid haemorrhage with special
      emphasis on the patient's view.
AB  - Although physical and emotional dysfunction appears to be quite frequent even
      among independent survivors of aneurysmal subarachnoid haemorrhage (SAH), these
      symptoms may easily be missed on routine follow-up examinations. To assess the
      long-term functional effects of SAH and to outline possible treatment approaches,
      a cross-sectional study using multidimensional measures of relevant areas of
      function was performed on 40 independent survivors. After an average follow-up
      period of 22 months, patients were selected and enrolled following a pre-designed
      protocol. The comprehensive test battery consisted of subjective and objective
      measures of physical, psychological and social function and relationships between
      the different levels of assessment were calculated. We found a considerable
      proportion of cognitive, emotional and physical dysfunction in this sample, but
      on the subjective level, the majority of the patients stated satisfaction with
      life in general. Mild cognitive dysfunction was frequently missed and causes
      distress in the family. Mild to moderate depression was underdiagnosed, although
      such an emotional dysfunction influences working capacity and quality of life.
      Referral to rehabilitation centers appears to be restricted to patients with
      severe impairments. Our results help to alert the neurosurgeon to these possible
      symptoms and show the urgent need for a prospective, interdisciplinary and
      multidimensional follow-up of SAH survivors.

PMID- 10929722
TI  - The extended transbasal approach: clinical applications and complications.
AB  - OBJECTIVES: To describe in detail key technical aspects of the extended
      transbasal approach which involves en-bloc mobilisation of the supraorbital rim,
      the orbital roof and the nasoethmoidal complex. In some patients osteotomies were
      performed around the cribriform plate with a view to maintaining olfaction. To
      review 18 patients with deep seated lesions located in the central skull base
      region (including 6 recurrences) to highlight patient selection, presentation,
      surgical morbidity and outcome. METHODS: Prospective data recording and clinical
      chart review. RESULTS: Outcome was assessed at a minimum of 1 year after
      operation using the Glasgow Outcome Score. Thirteen patients had made a good
      recovery, 1 was moderately disabled, 2 were severely disabled (both had been
      severely disabled before operation), and 2 died. By contrast, quality of life
      assessment indicated that only 7 of the surviving 14 adults had returned to
      normal levels of activity and perceived health; although 6 of the other 7
      patients had resumed their former occupations, their follow up assessments showed
      a reduced quality of life. Of the 13 patients who had an olfaction preservation
      procedure, 6 showed appreciation of smell on formal testing. CONCLUSIONS: In
      patients with progressive and extensive deep seated lesions this technique
      provides wide exposure in a shallow surgical field. Complication rates although
      acceptable were significantly higher in patients with intradural lesions. In some
      selected patients it was possible to preserve olfaction. Specific surgical
      outcome assessments pointed to satisfactory results, but failed to reflect the
      degree of patient disability. There is a need for outcome measures that take into
      account the patient's expectations and which address his quality of life in order
      to validate the benefits of these procedures.

PMID- 10929723
TI  - Posterior-fossa haemorrhage after supratentorial surgery--report of three cases
      and review of the literature.
AB  - We present clinical details of three patients with posterior fossa haemorrhage
      after supratentorial surgery and discuss possible pathomechanisms of this rare
      complication. All patients were males of advanced age. Two patients presented
      with a history of hypertension. In all patients the occurrence of haemorrhage was
      associated with loss/removal of large amounts of cerebrospinal fluid (CSF) either
      intra-operatively (one patient undergoing aneurysm surgery) or postoperatively
      (all three patients: drainage of subdural hygromas or chronic subdural haematomas
      in two, external ventricular drainage in one patient). Treatment consisted in
      haematoma evacuation and/or external ventricular drainage. Two patients died, one
      patient recovered completely. Although haematomas distant from a craniotomy site
      are a well known entity, a review of the literature identified only 25 published
      cases of posterior fossa haemorrhage after supratentorial procedures in the CT
      era. Most often disturbances of coagulation, positioning of the patient and
      episodes of hypertension have been associated with this complication. Only one
      author described the occurrence of a haemorrhage after drainage of a
      supratentorial hygroma. We suggest that the loss of large amounts of CSF intra
      operatively and post-operatively may lead to parenchymal shifts or a critical
      increase of transmural venous pressure with subsequent vascular disruption and
      haemorrhage.

PMID- 10929725
TI  - Cranial aneurysmal bone cyst "with special emphasis on endovascular management".
AB  - OBJECTIVE AND METHOD: Most of the literature about cranial aneurysmal bone cyst
      represents case reports, the aim of this paper is to gather information in solid
      clear statements about this disease in the region of the skull. This is a
      retrospective analysis of all available case reports on aneurysmal bone cyst
      involving the skull between 1960 and June 1998. The jaw was excluded. RESULTS:
      Sixty one cases of aneurysmal bone cyst involving the skull were found. 33 were
      males and 28 were females. The average age at presentation was 17.5 years. A
      painless enlarging mass was the most common mode of presentation. Features of
      pressure on intracranial structures with increased intracranial pressure were
      present in some patients. Most patients were managed by total excision of the
      lesion when feasible. Partial resection resulted in recurrence in some patients.
      Endovascular embolization has been used as a single mode of therapy or as pre
      operative to decrease the intra-operative bleeding. CONCLUSION: Aneurysmal bone
      cysts not uncommonly affect the skull. The pathological changes are similar to
      those affecting other parts of the body. Clinical presentation varies and depends
      on the part of the skull involved. Endovascular embolization plays a very
      important role in the management either as pre-operative or as the only method of
      treatment.

PMID- 10929724
TI  - Sporadic p53 mutations and absence of ras mutations in glioblastomas.
AB  - As concerns human adult brain neoplasms, the biological behaviour of
      glioblastoma, a high-grade neuro-ectodermal tumour, is among the most
      disadvantageous. Glioblastoma may develop either as a primary tumour without
      clinical and histological evidence of a prior precursor lesion, or as the final
      stage of malignant transformation of a low-grade or anaplastic astrocytoma. There
      are conflicting reports in connection with the association of the p53 tumour
      suppressor gene mutation with the clinical and histological progression of
      gliomas. Previous studies likewise led to contradictory results concerning the
      significance of ras oncogenes in different histological malignancies, and
      especially in neuro-epithelial tumours. The possible roles of p53 and ras gene
      alterations in the development of "primary" and "transformed" glioblastomas were
      studied in this work. Eighteen tumours were investigated by means of
      immunohistochemistry and polymerase chain reaction-assisted-single strand
      conformation polymorphism (PCR-SSCP) sequence analysis in a search for molecular
      genetic differences between primary and transformed glioblastomas. An increased
      incidence of p53-immunopositive cells was observed in both types of glioblastomas
      but there was no significant difference between the transformed tumours and the
      primary form. All samples were screened for point mutation in codons 12 and 61 of
      the H-, K-, and N-ras oncogenes and exons 5-8 of the p53 gene. No aberrant band
      or mutation was found in the H-, K- and N-ras oncogenes. Aberrant bands were seen
      in only 2 (11%) of the 18 tumours in the SSCP analyses of exons 6 and 8. Sequence
      analysis of the 2 abnormal cases revealed G --> C transmission in the second
      nucleotide of codon 280 on exon 8, which resulted in a change in the encoded
      amino acid from arginine to threonine (case 15). A ttagtct --> ttggtct
      transmission on intron 5 (case 8) was also found. No genetic difference could be
      identified between the primary and the transformed glioblastoma forms as concerns
      their p53 and ras oncogenes. There are two possible explanations for these
      findings: (a) The p53 and ras gene mutations were not primary events in the
      morphological transformations. Alterations in these genes may therefore take
      place at an early stage in glioma progression. (b) The different genetic changes
      may accumulate during glioblastoma development. These specific genetic events may
      additionally play a role in multistep tumourigenesis.

PMID- 10929726
TI  - Postoperative pain therapy after lumbar disc surgery.
AB  - OBJECT: This study was undertaken to determine whether a special postoperative
      pain administration of tramadol and diclofenac provides any benefits in patients
      who underwent microsurgical lumbar discectomy. METHODS: The study consisted of 60
      patients undergoing microsurgical lumbar discectomy. Patients were randomly
      divided into two groups based on the postoperative pain management: 1) Group A (n
      = 30); no standardized pain therapy; these patients received on demand different
      analgesics and at variable dosages which were selected by the neurosurgeons; 2)
      Group B (n = 30); standardized pain therapy with specific dosages of tramadol and
      diclofenac in regular time intervals during the first 48 hours after surgery.
      After surgery follow-up data from a special standardized questionnaire were
      obtained for all 60 patients during the first 48-72 postoperative hours. The
      patients were asked for course and intensity of pain as well as about some
      specific circumstances of clinical therapy after surgery. The postoperative pain
      intensity of patients treated with the special combination of tramadol and
      diclofenac was significantly diminished (24 hours after surgery: p = 0.0002, 48
      h: p = 0.0047, 72 h: p = 0.0034) in relation to the group without standardized
      pain therapy. Similarly, the frequency of breakthrough pain was significantly
      reduced (24 h: p = 0.0001, 48 h: p = 0.003, 72 h: p = 0.004). CONCLUSIONS: The
      results suggest that the application of tramadol and diclofenac during the first
      48 hours after lumbar microdiscectomy results in a reduction in postoperative
      pain without complications. We suggest that the use of this combination can be a
      beneficial adjunct to lumbar disc surgery.

PMID- 10929727
TI  - Nerve root signs on postoperative lumbar MR imaging. A prospective cohort study
      with contrast enhanced MRI in symptomatic and asymptomatic patients one year
      after microdiscectomy.
AB  - The association between postoperative nerve root signs and outcome was
      investigated in 54 out of one hundred patients operated on by lumbar
      microdiscectomy in a prospective cohort study with one year follow up. The
      patients were classified as failures or successes at the 12 month follow up
      according to a clinical overall score. All the 14 failures were investigated with
      MRI at the one year follow up, and 40 patients classified as successes were
      picked at random for MRI. Three patients with signs of recurrent disc herniation
      on MRI were excluded from the study. The MRI scans were independently read by two
      neuroradiologists who were ignorant of treatment outcome. No association between
      nerve root thickening, nerve root enhancement or nerve root displacement and the
      clinical outcome was found when patients with recurrent disc herniation were
      excluded.

PMID- 10929728
TI  - Surgically controlled, transpedicular methyl methacrylate vertebroplasty with
      fluoroscopic guidance.
AB  - The authors report a series of 13 patients with osteoporotic vertebral fractures
      treated by transpedicular vertebroplasty. Because of a neurological complication
      due to posterior leakage of acrylic cement the classical percutaneous approach
      was converted to an open surgical procedure. The latter allows direct visual
      control of neural structures and immediate removal of spilled cement, thus
      eliminating the danger of compressive, chemical and thermal effects of methyl
      methacrylate on neural elements. By use of this elegant technique primary
      stability of fractured vertebras is obtained leading to prompt pain relief in all
      patients. Surgically controlled vertebroplasty can be used in conjunction with
      internal fixation. By having studied the different ways of cement escape in their
      patients, the authors are convinced that surgically controlled vertebroplasty is
      safer than percutaneous vertebroplasty.

PMID- 10929729
TI  - Shunting effects in patients with idiopathic normal pressure hydrocephalus;
      correlation with cerebral and leptomeningeal biopsy findings.
AB  - Normal Pressure Hydrocephalus (NPH) is a potentially treatable syndrome with
      abnormal cerebrospinal fluid dynamics. Meningeal fibrosis and/or obliteration of
      the subarachnoid space have been suggested as one of the patho-anatomical
      substrates. However, other types of adult onset dementia, predominantly
      Alzheimer's disease and Vascular Dementia, may mimic the clinical NPH
      characteristics. The purpose of the present study was to correlate cerebral
      parenchymal and leptomeningeal biopsy findings to the clinical outcome after CSF
      shunting in a prospective group of idiopathic NPH (INPH) patients. The study
      comprises 27 patients with INPH, diagnosed and shunted according to generally
      accepted clinical, imaging and hydrodynamic criteria. In all patients a frontal
      leptomeningeal and brain biopsy was obtained prior to the shunt insertion.
      Degenerative cerebral changes, most often Alzheimer (6 cases) or vascular changes
      (7 cases) were described in 14 out of 27 biopsies. Arachnoid fibrosis was found
      in 9 of the 18 biopsies containing arachnoid tissue. Overall, nine patients (33%)
      improved, of whom 6 presented Alzheimer or vascular changes in their biopsies. No
      correlation was found between clinical outcome and the presence or absence of
      degenerative cerebral changes and/or arachnoid fibrosis. However, a tendency
      towards higher improvement rates was noted in the subgroups presenting
      degenerative cerebral changes or arachnoid fibrosis. The results suggest that no
      constant morphological element exists in the syndrome of INPH. Various
      aetiologies may be involved in the pathogenesis and possibly in some cases co
      existing: Patients may also improve by shunting despite the presence of
      degenerative cerebral parenchymal changes.

PMID- 10929730
TI  - Brain death and organ donation in Germany: analysis of procurement in a
      neurosurgical unit and review of press reports.
AB  - OBJECTIVE: A prospective study was undertaken to determine the number of
      potential organ donors in a neurosurgical intensive care unit and to record the
      actual number of organ donations. The reasons for refusal of organ donations were
      analysed with respect to the controversial public discussion of the brain death
      concept and the transplantation law in Germany. METHODS: From 1994 to 1997, the
      number of cases of brain death, and the number of cases in which relatives
      consented or refused to organ donation as well as the number of actual organ
      explantations was recorded. Over the same period, press reports of 5 German
      language newspapers were analysed with regard to the authors' position on brain
      death and transplantation law, their qualification, intention, and mode of
      presentation. RESULTS: Annually, about 70 deaths occurred on the department's
      intensive care unit of which almost 30% of the patients were determined to have
      suffered brain death without any obvious contraindications against organ
      donation. The refusal rate of relatives rose from 56% up to 78%, and the rate of
      organ donors thus decreased from 5% in 1994 to 4% presently in the department.
      About 100 reports were published each year in the analysed newspapers, of which
      about 90% voiced approval of organ transplantation. During the review period, the
      depiction became more objective (57% in 1994 to 82% in 1997) and the suspicious
      attitude toward the technique of brain death diagnosis declined. Whereas 50% of
      the articles rejected the brain death concept in 1994, this figure decreased to
      39% in 1997 and conversely the concept of consent rose from 33% in 1994 to 56% in
      1997. CONCLUSION: In Germany, the relatives refusal rate in organ donation is
      continuously high, presumable due to a depressing 39% of press reports rejecting
      the brain death concept, and resulting in a very low number of organ donations.
      There is hope that the transplantation law which has finally passed German
      parliament in 1997, confirming the brain death concept as well as the legal
      principle of prior consent by the donor or consent by the relatives will
      eventually result in an increase of organ donation especially when supported by
      an educational campaign which is embodied in the transplantation law.

PMID- 10929731
TI  - Identification of somatosensory pathways by focal-cooling-induced changes of
      somatosensory evoked potentials and EEG-activity--an experimental study.
AB  - OBJECT: Function-preserving neurosurgery requires methods to identify
      functionally important CNS-areas intraoperatively. We investigated whether a
      combination of focal cerebro-cortical cooling and monitoring of somatosensory
      evoked potentials (SEP) is suited for this task, i.e. whether it is able to
      outline structures belonging to the somatosensory pathway. METHODS: In 17 Wistar
      rats the somatosensory cortex was focally cooled by 20 degrees C below the
      initial tissue temperature for periods of five minutes. A cryoprobe with a tip
      diameter of 3 mm was used and tissue temperatures were measured below and at
      different distances to the cryoprobe. Tibial nerve evoked SEPs and EEG-spectra
      were recorded continuously. RESULTS: During cortical cooling the SEP-responses
      showed a marked delay and amplitude increase of the cortically generated
      components P13 and N18 and a small latency increase of the subcortically
      generated wave III. EEG-spectra were depressed mainly in the low frequency range.
      All cooling effects were reversible and in light- as well as electron-microscopic
      examinations no tissue damage was found. CONCLUSIONS: Focal cooling of the cortex
      induces easily recognizable and reversible changes of the bio-electrical activity
      without causing any histological damage. Therefore the method seems suitable for
      identifying eloquent areas. It can be expected that clinical application of the
      cooling technique in combination with intraoperative electrophysiological
      monitoring will be helpful to further lower the risk of neurosurgical operations.
      We propose that cooling mainly interferes with the synaptic transmission within
      the somatosensory cortex, because the observed amplitude increase can be
      explained by cold-induced depression of inhibitory cortical activity
      (disinhibition).

PMID- 10929732
TI  - Vertebral artery to common carotid artery bypass in Takayasu's disease with
      delayed cerebral ischemia.
AB  - Takayasu's Arteritis is a progressive occlusive disease of the aortic arch and
      its branches. It may need several bypass procedures along with or without
      endovascular techniques. CASE DESCRIPTIONS: A twenty-six year old woman who had a
      history of Takayasu's Arteritis, and had a Gore-Tex Dacron Y-graft from the
      ascending aorta to the right subclavian and right common carotid arteries 18
      years before, is presented. She presented with recurrent hemispheric ischemia and
      transient ischemic attacks and severe long segment stenosis in the left common
      carotid artery. She was successfully treated with a saphenous vein graft bypass
      from the left vertebral artery to the common carotid artery. The stenosis of the
      brachiocephalic graft was successfully treated by angioplasty. Three months
      follow up showed stenosis of the left VA immediately proximal to the proximal
      anastomosis which was managed successfully with angioplasty. CONCLUSIONS: The
      surgical treatment of Takayasu's Arteritis with bypass procedures needs a complex
      overview and follow up. A regular follow up is mandatory for evaluation and
      planning of appropriate management, in view of the progressive nature of the
      disease process.

PMID- 10929733
TI  - Spinal cord tumour simulated by an infarction of the conus medullaris.

PMID- 10929734
TI  - Marfan syndrome associated with moyamoya phenomenon and aortic dissection.

PMID- 10929735
TI  - Emergency evacuation of expanding intracerebral haemorrhage in parahaemophilia
      (coagulation factor V deficiency).

PMID- 10929736
TI  - Remote lesion in the substantia nigra caused by striatopallidal abscess.

PMID- 10929737
TI  - Olfactory groove schwannoma revisited.

PMID- 10929738
TI  - The actual meaning of "urgency" in the practice of heart transplantation.

PMID- 10929740
TI  - Primary coronary angioplasty in acute myocardial infarction: is it possible to
      prevent postinfarction cardiac rupture?
AB  - BACKGROUND: Cardiac rupture is a leading cause of death among patients
      hospitalized for acute myocardial infarction (AMI). The aim of our retrospective
      study was to evaluate the impact of primary coronary angioplasty (PTCA) on this
      not common but usually fatal complication. METHODS: Since January 1998 PTCA has
      been the routine treatment for AMI patients in our Institution monitored during
      the first 12 hours from symptom onset. The AMI patients hospitalized between
      January 1998 and December 1999 (Group A) were retrospectively compared to those
      observed between January 1996 and December 1997 (Group B, historical control
      group), mainly treated with systemic thrombolysis. Patients hospitalized after 12
      hours of symptom onset were excluded from the study. Data were analyzed on an
      intention-to-treat design. RESULTS: Group A consisted of 204 patients (148 males,
      56 females, mean age 67 +/- 11 years), 165 (81%) of whom underwent coronary
      angiography. Group B consisted of 185 patients (123 males, 62 females, mean age
      71 +/- 12 years), 78 (42%) of whom were treated with thrombolysis and 33 (18%)
      with PTCA. The groups did not differ as regards the time delay before hospital
      entry, Killip class at admission and site of AMI. Fourteen patients (6.8 %) of
      Group A and 20 (10.8%) of Group B died in the Cardiology Division. No deaths due
      to cardiac rupture were observed among the 165 Group A patients, nor among the 33
      Group B patients treated with PTCA. Cardiac rupture was the cause of death for 1
      out of 14 (7%) patients in Group A, and for 8 out of 20 (40%) patients in Group B
      (p < 0.02 Group A vs Group B). Nine Group A patients and 11 Group B patients died
      because of cardiogenic shock. CONCLUSION: A lower cardiac rupture incidence was
      observed among Group A patients in comparison to those of Group B. Thus our data,
      although not randomized, suggest the ability of primary PTCA in preventing post
      AMI cardiac rupture.

PMID- 10929739
TI  - First risk functions for prediction of coronary and cardiovascular disease
      incidence in the Gubbio Population Study.
AB  - BACKGROUND: The Gubbio study is an Italian population study which measures the
      risk factors and incidence of major cardiovascular diseases. This analysis
      produces multivariate models for the prediction of cardiovascular end-points.
      METHODS: A population sample of 2,963 men and women aged 35-74, free from major
      cardiovascular diseases, was examined in 1983 with risk factor measurement, and a
      6-year incidence was computed for coronary heart disease and all cardiovascular
      (atherosclerotic) events. Proportional hazards models were solved for the
      prediction of these events. RESULTS: Over a 6-year period, 74 hard criteria, and
      126 any criterion coronary heart disease and 174 cardiovascular events were
      recorded. Multivariate models showed the predictive power of sex (relative risk
      ranging 1.63 to 2.60), age (relative risk for 5-year difference ranging 1.38 to
      1.48), systolic blood pressure (relative risk for 20 mmHg difference ranging 1.17
      to 1.27), HDL cholesterol (relative risk for a difference of 10 mg/dl ranging
      0.73 to 0.81), non-HDL cholesterol (relative risk for 40 mg/dl difference ranging
      1.15 to 1.27), cigarette smoking (relative risk for 10 cigarette difference
      ranging 1.21 to 1.28), and body mass index (relative risk for 3 units ranging
      0.99 to 1.02). All coefficients were statistically significant except that for
      body mass index, they were larger for hard criteria coronary heart disease, and
      their magnitude was similar to that found in previous Italian population studies.
      CONCLUSIONS: Traditional cardiovascular risk factors predict coronary and
      cardiovascular events in another Italian population study confirming previous
      findings and similar predictive models.

PMID- 10929741
TI  - Detrimental effects of acute heparin administration on ischemic threshold in
      patients with coronary artery disease.
AB  - BACKGROUND: Recent studies have indicated that heparin administration might
      decrease endothelial nitric oxide production. The aim of this study was to
      investigate the effect of heparin on ischemic threshold. METHODS: Eighteen
      patients with a positive exercise test and proven coronary artery disease were
      submitted to a randomized, placebo-controlled trial using i.v. 0.9% NaCl as
      placebo and i.v. heparin (5,000 IU bolus + 1,000 IU/h). After both saline and
      heparin bolus, the infusion was started and, after 10 min, the exercise test was
      performed. Blood samples for nitric oxide metabolites and free fatty acid
      determinations were taken before, at peak exercise, and at ECG recovery. RESULTS:
      As compared to placebo, heparin significantly decreased time to 1 mm ST segment
      depression (241 +/- 160 vs 303 +/- 175 s, p = 0.003) and prolonged recovery (573
      +/- 177 vs 441 +/- 195 s, p = 0.003), while exercise duration was similar.
      Accordingly, rate-pressure product at 1 mm ST segment depression was lower after
      heparin, while it was similar at peak exercise. No significant differences were
      found for plasma nitric oxide metabolite levels. Conversely, free fatty acid
      levels were higher after heparin throughout the study in all patients. The
      increase in free fatty acids was not correlated with the difference in rate
      pressure product at 1 mm ST segment depression between placebo and heparin (r =
      0.34, p = NS). CONCLUSIONS: In patients with stable coronary artery disease,
      heparin significantly decreased exercise ischemic threshold. The lower rate
      pressure product at 1 mm ST segment depression during heparin, compared to
      placebo, suggests an impairment of coronary blood flow, which does not seem to be
      mediated by decreased nitric oxide production/release. The increased free fatty
      acid release, on the other hand, might contribute to the detrimental effect of
      heparin on exercise-induced ischemia, but the lack of a correlation with changes
      in ischemic threshold suggests that other, still unknown, factors are involved.

PMID- 10929742
TI  - Automatic atrial tachyarrhythmia detection from intracardiac electrograms.
AB  - BACKGROUND: Automatic atrial tachyarrhythmia recognition is crucial in order to
      allow a correct switching-mode function of dual-chamber pacemakers and to avoid
      inappropriate shocks of ventricular implantable cardioverter-defibrillators. In
      this paper we considered three algorithms suitable for implantable devices. The
      first was based on the atrial cycle length; the others analyze different
      morphologic characteristics of atrial signals. METHODS: Intracardiac bipolar
      electrogram recordings were obtained from the high right atrium during
      electrophysiological study. Twenty patients were considered, some of them
      presenting with different types of cardiac rhythm at different intervals of the
      study. Cardiac rhythms were divided into three groups: sinus rhythm consisting of
      2,196 s obtained from 12 subjects, atrial fibrillation consisting of 771 s
      obtained from 7 subjects, and atrial flutter consisting of 1,793 s obtained from
      7 subjects. The automatic detection was performed on each electrogram segment
      lasting 1 or 4 s. Atrial segments were separated into two subgroups: the first
      for the training of the algorithm and the second for testing and validation of
      results. We considered two types of statistical analysis: comparison between
      pairs of rhythm (paired classification), and classification among the three
      different groups (direct classification). RESULTS: The combination of the cycle
      length algorithm with a morphological method achieved the best performance for
      both statistical analyses. Paired classification resulted in the following:
      atrial fibrillation vs sinus rhythm was detected with no error; atrial flutter vs
      sinus rhythm with a total accuracy of 99.3% (sensitivity 99.4%, specificity
      99.2%); atrial fibrillation vs atrial flutter with a total accuracy of 99.1%
      (sensitivity 98.5%, specificity 99.4%). The total accuracy achieved for the
      direct classification was 98.6% (average sensitivity 98.5%, specificity 98.8%).
      CONCLUSIONS: Our results support the association of algorithms for future
      enhancement of atrial tachyarrhythmia detection in dual-chamber devices, thanks
      to the limited computational effort.

PMID- 10929743
TI  - Multivessel coronary stenting: predictors of early and late outcome.
AB  - BACKGROUND: At present, only few data are available on the early and late outcome
      following multivessel coronary stenting. Of note, in these studies, the left
      anterior descending (LAD) artery was treated in less than 40% of cases. These
      patients may not fully represent the population commonly referred for surgical
      revascularization. METHODS: In-hospital and long-term (18 +/- 4 months) events
      were evaluated in 272 consecutive patients who had multivessel stent implantation
      including the LAD artery in each case. All clinical, angiographic, and procedural
      variables were analyzed to identify the predictors of acute and long-term major
      adverse coronary events. RESULTS: Eighteen patients (6.6%) had in-hospital major
      adverse coronary events (death 0.7%, coronary artery bypass grafting 0.4%, and
      myocardial infarction 6.3%). Acute and subacute stent thrombosis rates were 1.5
      and 1.1%, respectively. At 18 +/- 4 months, event-free survival was 71%. Target
      lesion revascularization was performed in 54 (20%) patients (42 coronary
      angioplasty and 12 coronary artery bypass grafting). The jeopardy score was the
      predictor of in-hospital major adverse coronary events (p = 0.016, odds ratio
      1.34, 95% confidence interval 1.05-1.69), and diabetes mellitus was the predictor
      of long-term major adverse coronary events (p = 0.027, odds ratio 2.80, 95 %
      confidence interval 1.12-6.96). CONCLUSIONS: Multivessel coronary stent
      implantation with treatment of the LAD artery in all instances is a safe
      procedure with low acute and long-term major adverse coronary events. The risk
      benefit ratio must be assessed carefully for each patient, particularly taking
      into account the jeopardy score and the presence of diabetes mellitus.

PMID- 10929744
TI  - Modulation of vascular endothelial gene expression by physical training in
      patients with chronic heart failure.
AB  - BACKGROUND: Abnormalities of the skeletal muscle vasculature, such as endothelial
      dysfunction and reduced microvascular density, can be reversed by physical
      training in patients with chronic heart failure. The molecular mechanisms that
      mediate the beneficial effects of physical training on the vascular endothelium
      are unknown. METHODS: Endothelial nitric oxide synthase (eNOS) and vascular
      endothelial growth factor (VEGF) gene expression in the skeletal muscle, peak
      oxygen consumption (VO2) and calf peak reactive hyperemia were measured before
      and after 12 weeks of supervised physical training in 10 patients with chronic
      heart failure. Five patients with heart failure of similar severity who did not
      participate in the training program served as controls. RESULTS: The effects of
      physical training on eNOS and VEGF gene expression were heterogeneous. eNOS gene
      expression increased 3-4 fold in 4 patients while it remained constant in 6
      patients. VEGF gene expression increased significantly in all patients who were
      not treated with beta-adrenergic blockade and remained constant in all patients
      who were treated with beta-adrenergic blockade. In contrast, physical training
      increased peak VO2 and calf peak reactive hyperemia in all patients. Mean peak
      VO2 increased from 13.13 +/- 2.21 to 16.19 +/- 2.69 ml/kg/min (p < 0.001) and
      calf peak reactive hyperemia increased from 19.7 +/- 2.3 to 29.6 +/- 4.0 ml*min(
      1)*100 ml(-1) (p < 0.001). CONCLUSIONS: A supervised program of physical training
      that consistently enhanced peak VO2 and vascular reactivity in patients with
      chronic heart failure increased or left eNOS and VEGF gene expression unchanged
      in skeletal muscle. Changes in vascular endothelial gene expression may
      contribute to the benefits of training on vascular endothelial function but are
      not solely responsible for these benefits.

PMID- 10929745
TI  - Myocardial ischemia caused by an hydatid cyst of the interventricular septum
      successfully treated with albendazole.
AB  - We report the case of a 33-year-old patient with clinical history of
      echinococcosis admitted to our Hospital for the appearance of chest pain and
      electrocardiographic findings of anterior ischemia. The cardiac enzymogram was in
      the normal range, the chest roentgengram did not show any pathological findings,
      but two-dimensional echocardiography revealed the presence of a small circular
      area in the interventricular septum. Transesophageal echocardiography and cardiac
      nuclear magnetic resonance confirmed the presence of a small hydatid cyst in the
      middle ventricular septum; in addition, a myocardial scintigraphy revealed an
      apical stress defect with late reperfusion. Besides cardiologic therapy, the
      patient was treated with albendazole, an antiparasitic drug, 400 mg bid, for
      cycles of 28 days with 14 day withdrawal. After two cycles of albendazole
      therapy, two-dimensional echocardiography showed the absence of the round cystic
      mass of the interventricular septum previously described. In conclusion, in the
      case described, long-term therapy with albendazole determined the complete
      recovery from the illness with the simultaneous disappearance of the cyst and of
      clinical and electrocardiographic findings of myocardial ischemia.

PMID- 10929746
TI  - Extraskeletal mesenchymal chondrosarcoma involving the heart: report of a case.
AB  - Extraskeletal mesenchymal chondrosarcoma is a rare tumor frequently arising in
      the meninges and lower limbs. We describe a case of mesenchymal chondrosarcoma
      involving the heart in a 39-year-old man who presented with fever, chest pain and
      shortness of breath. His clinical course was rapid, leaving insufficient time for
      a complete diagnostic work-up, and the patient died 2 months after the onset of
      symptoms.

PMID- 10929747
TI  - Images in cardiovascular medicine. A malignant peripheral nerve sheath tumor
      presenting as an intrapericardial mass.

PMID- 10929749
TI  - Continuing the discussion: managed care--boon or boondoggle?

PMID- 10929748
TI  - The limitations and promise of health education in managed care.
AB  - Managed care has become the predominant form of health insurance in the United
      States. With its features of capitation, provider monetary risk, and population
      perspective, managed care represents a huge growth opportunity for advocates of
      disease prevention and health promotion, including those in the field of health
      education. In reality, however, health education's role has fallen far short of
      expectations. This article is presented to initiate a dialogue on the role of
      health education and its subset, worksite health promotion, within managed care.
      The worksite is emphasized because of its attractiveness as a site in delivering
      population-based medicine. Furthermore, employers exercise considerable influence
      in shaping the health care marketplace. A list of recommendations is presented,
      offering suggestions on what health education needs to do to increase its impact
      in the managed care movement. These arguments are posed to better position this
      profession in a changing health care environment.

PMID- 10929750
TI  - On contemplation at 50: SOPHE Presidential address, November 1999. Society for
      Public Health Education.

PMID- 10929751
TI  - Finding the "community" in community-level HIV/AIDS interventions: formative
      research with young African American men who have sex with men.
AB  - Data from 76 qualitative interviews with 18- to 29-year-old African American men
      who have sex with men (MSM) in Chicago and Atlanta were examined to identify
      perceptions of "community" and components of a community-level HIV/AIDS
      intervention. Many men reported feeling marginal to African American and gay
      White communities because of perceived homophobia and racism. Those who reported
      feeling part of gay African American communities characterized communities in
      terms of settings, social structures, and functions, including social support,
      socialization, and mobility. Despite these positive functions, divisions among
      groups of MSM, lack of settings for nonsexual interaction with other MSM, lack of
      leadership, and negative attitudes toward homosexuality may make it difficult for
      men to participate in activities to alter community contexts that influence
      behavior. Rather, changing norms, increasing social support, and community
      building should be part of initial community-level interventions. Community
      building might identify leaders, create new settings, and create opportunities
      for dialogue between MSM and African American community groups to address
      negative perceptions of homosexuality.

PMID- 10929752
TI  - Using communicative action in the primary prevention of cancer.
AB  - The primary prevention of disease, including cancer, has been a major part of
      health promotion and health education for decades. However, the long-term results
      of these strategies have been mixed, and primary prevention as an instrument of
      cancer control continues to fail to live up to either public or professional
      expectations. The authors identify and critique two possible factors contributing
      to this failure and then offer a model for the development and implementation of
      primary prevention strategies that addresses these factors. The model used is
      based on Habermas's theory of communicative action and recognizes the importance
      of a critical dialogue in health education and health promotion. The primary
      prevention programs currently being conducted by the Cancer Centre for the
      Southern Interior are presented as an example of the model in action.

PMID- 10929753
TI  - The impact of a culturally appropriate STD/AIDS education intervention on black
      male adolescents' sexual and condom use behavior.
AB  - A culturally appropriate, theoretically based videotape was developed to promote
      condom use among African American males, ages 15 to 19, attending a municipal
      sexually transmitted disease (STD) clinic. The videotape's impacts were compared
      to those achieved by an African American health educator who delivered the same
      messages during a face-to-face session and by standard care. Data were obtained
      on participants' (N = 562) condom use knowledge, self-efficacy, and intentions;
      sexual and condom use behaviors; and perceived risk of infection. At posttest,
      "videotape" and "health educator" participants demonstrated greater condom use
      knowledge; "health educator" participants indicated greater self-efficacy and
      stronger condom use intentions with steady partners. At 6 months, participants in
      all conditions reported more partners and acts of vaginal intercourse (past
      month); however, they were more likely to report consistent condom use with
      steady partners (18% vs. 53%) and casual partners (26% vs. 50%). Perceived risk
      of infection was lower at the posttest and declined during the study period.

PMID- 10929755
TI  - The relationship between organizational characteristics and the adoption of
      workplace smoking policies.
AB  - Organizational-level variables that are hypothesized to influence the level of
      smoking policy restrictions and the prevalence of smoking control activities were
      tested in a sample of 1 14 worksites that participated in the Working Well Trial,
      a national trial of worksite health promotion. Predictors related to more
      restrictive policies included smaller size, larger percentage of white-collar
      workers, larger number of complaints about environmental tobacco smoke, less
      complexity, more formalization, and having a CEO who valued health and employees'
      well-being. The number of smoking control activities offered in a worksite was
      predicted by having a larger blue-collar workforce, a higher percentage of female
      employees, higher levels of workforce stability, and a CEO who valued health and
      employees' well-being. Efforts to identify predictors of companies' adoption and
      implementation of workplace-based policies and interventions are an important
      part of tobacco control efforts and will enhance future intervention and research
      efforts.

PMID- 10929754
TI  - The role of availability as a moderator of family fruit and vegetable
      consumption.
AB  - The public health objective to improve the diet of Americans includes increasing
      the consumption of fruits and vegetables (F&V). The availability of F&V in the
      home has been suggested but not confirmed as one environmental factor that
      influences the types and quantities of F&V eaten by family members. Using a model
      of parental and child influences on a child's intake of F&V, the authors
      investigated F&V availability as a moderating variable for the relationships
      between the model constructs and how the relationships might change with varying
      levels of F&V availability. Path analysis and multigroup structural equation
      modeling were the analytic tools. Results indicated that homes with more F&V
      available had a richer and generally stronger set of motivating factors for
      parent and child F&V consumption than homes with low F&V availability. Findings
      have implications for parental involvement in interventions to enhance the diet
      of fourth-grade children.

PMID- 10929756
TI  - Sex workers' perspectives on condom use for oral sex with clients: a qualitative
      study.
AB  - The authors conducted in-depth interviews with 46 female brothel-based sex
      workers to explore their perceived barriers and approaches in getting clients to
      use condoms for oral sex. Reasons given by sex workers for not using condoms for
      oral sex as compared to vaginal sex included self-perception of low vulnerability
      to AIDS and sexually transmitted infections, misconceptions on transmission of
      the HIV virus, lack of negotiation skills, lack of support from brothel keepers
      and peers, and unpleasant taste and smell of condoms. Some sex workers could get
      all their clients to use condoms for oral sex by using negotiation skills,
      including the positive approach, the fear approach, the emotional appeal
      approach, and the assertive approach. Findings from this study would help design
      more appropriate messages and improve negotiation skills of sex workers to
      increase consistent condom use for oral sex.

PMID- 10929757
TI  - Pathology of small-cell lung cancer.
AB  - The morphological differentiation between small-cell and non-small-cell lung
      cancer has great prognostic and therapeutic significance for the patient.
      Malignant lung tumors are now classified according to the new 1999 WHO/IASLC
      classification of lung and pleural tumors. The variant of heterogeneously
      differentiated "combined small-cell carcinoma" can be distinguished from
      classical small-cell carcinoma, whereas the subtype of "intermediate cell
      carcinoma" is no longer used. Together with "large-cell neuroendocrine
      carcinomas" and typical or atypical carcinoid tumors, small-cell lung cancers are
      currently histogenetically categorized as neuroendocrine lung tumors. In contrast
      to large-cell neuroendocrine carcinoma, the immunohistochemical demonstration of
      neuroendocrine differentiation is not a prerequisite for the diagnosis of small
      cell lung cancer. Although electron-microscopical, immunohistochemical, and
      molecular-biological findings have considerably increased our understanding of
      the pathogenesis and progression of malignant lung tumors, routine pathological
      anatomical diagnostics are still decisively based on light-microscopical
      evaluation of tissue samples.

PMID- 10929758
TI  - Geriatric assessment in the elderly cancer patient.
AB  - Lost and remaining functions are of special importance in geriatric medicine. The
      level of functional deficits ultimately determines the remaining quality of life
      and the patient's ability to continue independently. In contrast, the actual
      severity of a disease measured by common standards becomes less important.
      Geriatric assessment is increasingly used to describe the impact of disease and
      to focus on the functional losses and problems that are particularly relevant to
      the individual elderly patient. When developing a treatment plan for older cancer
      patients, it is essential to consider the functional deficits caused by age
      related changes or comorbidity, the remaining compensation mechanisms and the
      patient's expectations. Cancer treatment has to be adapted to the individual
      needs of elderly patients. As the number of cancer patients is rising in all
      areas of medical practice, a close collaboration between oncologists and
      geriatricians will become increasingly important.

PMID- 10929759
TI  - Expression of blood group antigens A, B and H in carcinoma tissue correlates with
      a poor prognosis for colorectal cancer patients.
AB  - The deletion of blood group ABH isoantigens on tumor tissues has been reported to
      be an adverse prognostic marker for patients with various solid tumors. In the
      present study, we evaluated the prognostic value of altered expression of ABH
      isoantigens in colorectal carcinomas. Using monoclonal antibodies, the expression
      of A, B, and H antigens was assessed by immunohistochemistry on paraffin-embedded
      carcinoma samples from 82 patients who had undergone surgery for colorectal
      cancer. ABH isoantigens were found to be deleted in 36 carcinomas (43.9%) and
      expressed in 46 (56.1%). Univariate and multivariate analysis using a logistic
      regression model revealed that N factor (lymph node metastasis) and blood group
      type were independently related to the expression of ABH isoantigens. In contrast
      to previous reports on other cancers, patients whose colorectal carcinomas
      express ABH isoantigens had a poorer prognosis than those whose carcinomas showed
      deletion of ABH isoantigens (P = 0.0008). The expression of ABH isoantigens was
      an independent prognostic variable, in addition to T (depth of tumor invasion),
      N, and M (distant metastasis) factors, as shown by means of Cox regression
      analysis. In conclusion, the expression of ABH isoantigens in carcinoma tissue is
      an important poor prognostic factor in patients with colorectal cancer. This
      variable needs to be considered in the design of future trials of therapy.

PMID- 10929760
TI  - Eligibility of antigenic-peptide-pre-loaded and fixed adhesive peripheral blood
      cells for induction of cytotoxic T lymphocytes from cancer patients with elevated
      serum levels of carcinoembryonic antigen.
AB  - The inducibility of cytotoxic T lymphocytes (CTL) that react with
      carcinoembryonic antigen (CEA) was tested in cancer patients with elevated (more
      than 5 ng/ml) serum CEA levels when antigen presentation was carried out with
      paraformaldehyde-fixed adhesive peripheral blood mononuclear cells (PBMC) from
      the patient that had been pre-loaded with CEA652(9), an HLA-A2402-restricted
      tumor antigenic peptide derived from CEA. By culturing fresh autologous PBMC on
      the fixed cell layer in medium containing interleukin-1, -2, -4 and -6. three out
      of eight patients developed CTL. The CTL from two of these patients killed CEA
      protein-producing gastric cancer cells carrying HLA-A2402 and the cells from the
      remaining patient killed CEA-non-producing stomach cancer cells pre-loaded with
      CEA652(9). The results suggest that a single antigenic peptide on the fixed
      adhesive cells will allow the ex vivo induction of peptide-reactive CTL that are
      easier to handle and allow antigen presentation without tedious preculture of the
      "professional" antigen-presenting dendritic-cells.

PMID- 10929761
TI  - Type and position of promoter elements in retroviral vectors have substantial
      effects on the expression level of an enhanced green fluorescent protein reporter
      gene.
AB  - PURPOSE: Although gene transfer with retroviral vectors has already been applied
      to patients as part of clinical protocols, low expression of transgenes in target
      cells still remains a problem. Therefore, we compared various retroviral vectors
      using different promoters and backbones for expression of the enhanced green
      fluorescent protein (EGFP) reporter gene in fibroblasts and CD34+ cells. METHODS:
      The N2A retroviral vector was used to test expression from the herpes simplex
      virus thymidine kinase promoter (vector N2A-TK-EGFP), a human phosphoglycerate
      kinase promoter (vector N2A-PGK-EGFP), and the SV40 promoter (vector N2A-SV
      EGFP). Additional constructs used the spleen focus-forming virus (SFFV) long
      terminal repeat (LTR) as promoter and expressed EGFP alone (vector SFbeta1-EGFP)
      or EGFP and a downstream (vector SFbeta1-EGFP-IRES) or upstream (vector SFbeta1
      IRES-EGFP) internal ribosomal entry site. RESULTS: For NIH 3T3 cells the
      fluorescence-activated cell sorting analysis revealed that the most active
      internal promoter was the SV40 promoter in the vector N2A-SV-EGFP (mean
      fluorescence intensity, MFI, 66.7 +/- 0.4), followed by N2A-PGK-EGFP (26.3 +/-
      1.8 MFI), and N2A-TK-EGFP (4.8 +/- 0.1 MFI). Expression from the SFbeta1-EGFP
      vector (82.6 +/- 6.7 MFI) and the SFbeta1-EGFP-IRES vector (102.8 +/- 6.2 MFI)
      was higher than from SFbeta1-IRES-EGFP vector (15.5 +/- 1.8 MFI). In human CD34
      positive cells, the EGFP expression from all vectors was considerably lower than
      in fibroblasts with the SFbeta1-EGFP vector still being four- to fivefold more
      active than the internal promoters tested. CONCLUSION: The SFFV LTR seems to
      allow a high expression of transgenes, as long as the transgene is not expressed
      downstream of an internal ribosomal entry site. Internal promoters may be useful
      for targeted gene expression in specific cell types, but the reduced level of
      expression from some internal promoters has to be taken into consideration.

PMID- 10929762
TI  - Identification of differentially expressed genes in nasopharyngeal carcinoma by
      means of the Atlas human cancer cDNA expression array.
AB  - PURPOSE: To investigate genes of critical areas, including cell cycle/growth
      control, apoptosis, oncogene/tumor suppressors and growth factor/cytokines, that
      are differentially expressed in nasopharyngeal carcinoma. METHODS: The Human
      Cancer cDNA Atlas, which contains 588 genes relating to tumor biology, was used
      to screen normal nasopharyngeal tissue, nasopharyngeal cancer (NPC). The reverse
      transcription/polymerase chain reaction was used to confirm the expression
      pattern of some genes identified by Atlas hybridization. RESULTS: The
      differentially expressed cell cycle/growth control regulators in NPC showed a
      stronger tendency toward cell proliferation with the up-regulation of cyclin D1,
      cyclin D2 etc. The expression pattern of apoptosis-related genes demonstrated the
      up-regulation of both anti-apoptotic factors such as the BCL-2-related protein
      A1, TRAF3, the inhibitor of apoptosis protein A1 (IAPI) and apoptotic pathway
      elements such as Fas/Apo-1, Apo-2 ligand etc. Among oncogenes/tumor suppressors,
      MDM2, STAT1 and STAT2 were found to be up-regulated in NPC. The expression
      profile of growth factors/cytokines showed the up-regulation of many growth
      enhancing factors such as EGR1, tumor-derived growth factor 1, platelet-derived
      growth factor A chain etc. as well as Th1-type cytokines e.g. interleukin-1beta
      and interferons. A smaller number of genes were down-regulated in nasopharyngeal
      cancer, such as those encoding ERK1, Raf, secreted apoptosis-related protein 1,
      CD27BP, transforming growth factor beta2, pre-B-cell-stimulating factor homologue
      etc. CONCLUSION: The consistent tendency toward cell proliferation, the
      possibility of a stronger antiapoptotic force that operates on the normal
      apoptotic pathway, or the autocrine or paracrine growth factors may account for
      the development of NPC. Some genes are reported for the first time to have
      changed expression in nasopharyngeal carcinoma. The simple, quick, and high
      throughput method of profiling gene expression by cDNA array hybridization
      provides us with a quick overview of key factors that may be involved in NPC, and
      may identify genes suitable for further study of carcinogenesis mechanism or
      targets for possible molecular diagnosis or therapy.

PMID- 10929763
TI  - Comparative analysis of methotrexate polyglutamates in lymphoblast preparations
      from bone marrow and blood, and the contribution of residual red blood cells.
AB  - PURPOSE: Blasts isolated from bone marrow aspirates or blood samples of patients
      with acute lymphoblastic leukemia (ALL) or acute myelogenous leukemia (AML) were
      compared for uptake of methotrexate (MTX) and formation of MTX polyglutamates
      (MTX-Glu(n)). Red blood cells (RBC) from the same patient samples were also
      analyzed. METHODS: Blasts were isolated by standard density centrifugation. RBC
      were prepared from the pellet of the same centrifugation. MTX-Glu(n) were
      analyzed by means of HPLC and radiochemical quantification. RESULTS: In
      lymphoblasts isolated from blood, the distribution patterns of MTX-Glu(n) were
      the same as in bone marrow lymphoblasts, but the total amount of MTX-Glu(n)
      accumulated in blood lymphoblasts was reduced by 41% 51% when compared to the
      same number of bone marrow lymphoblasts of the same patient. RBC accumulated MTX
      but no formation of MTX-Glu(n) occurred. CONCLUSIONS: The determination of MTX
      and MTX-Glu(n) in lymphoblasts isolated from blood samples of patients with
      common ALL provides qualitative information on the capacity of the blasts to form
      MTX-Glu(n) since distribution patterns of MTX and MTX-Glu(n) parallel that of
      bone marrow lymphoblasts. The amounts of MTX-Glu(n) accumulated, however, were
      much lower in blood lymphoblasts. Blood lymphoblasts are therefore not useful for
      a quantitative analysis of MTX-Glu(n). The contribution of RBC to MTX and MTX
      Glu(n) in vitro is only marginal and residual RBC in lymphoblast preparations
      from bone marrow can therefore be ignored.

PMID- 10929764
TI  - Malignancies in patients with insulin-treated diabetes mellitus.
AB  - In patients with diabetes mellitus, contradictory results have been reported
      indicating both increased and reduced risks of malignancies. In the present trial
      all insulin-treated diabetic patients (n = 2720) attending our centre since 1995
      were studied. Of these patients, 28 (type 1/type 2: n = 1/27, 23 women) developed
      malignancies during insulin therapy: 11 patients developed cancer of the breast,
      4 patients cancer of the pancreas, 3 patients cancer of the kidneys and 10
      patients developed other malignancies. The characteristics of these patients
      [mean +/- SD (range)] were as follows: age 68.8 +/- 8.6 (52.0 87.0) years,
      diabetes duration 13.1 +/- 8.1 (0.5-29.0) years, duration of insulin therapy at
      the time of the diagnosis of malignancy 4.3 +/- 5.7 (0.5 24.0) years, insulin
      dosage 0.67 +/- 0.43 (0.11-1.72) IU/kg body weight, mean HbAlc 9.6 +/- 1.9 (6.8
      14.9)% (HPLC, Diamat, normal range 4.4%-5.9%). The prevalences of nephropathy,
      retinopathy (non-proliferative: n = 7) and peripheral neuropathy were 35.7%,
      25.0% and 46.4% respectively. When the features of the 27 patients with type 2
      diabetes were compared with the characteristics of the type 2 diabetic patients
      (n = 117, 63 women) studied in a population-based survey of insulin-treated
      diabetic patients, also performed in the area of Jena [JEVIN; Schiel R et al.
      (1997a)] there were no significant differences in the duration of insulin therapy
      (JEVIN: 4.7 +/- 4.3 years, P = 0.64), insulin dosage (JEVIN: 0.55 +/- 0.27 IU/kg
      body weight, P = 0.08), mean HbAlc (JEVIN: 9.0 +/- 2.1%, P = 0.16) and the
      prevalences of long-term complications of diabetes. The quality of diabetes
      control in insulin-treated patients suffering from malignancies is comparable to
      that of a selection-free population of diabetic patients. Furthermore, in
      comparison to non-diabetic subjects our diabetic patients showed no altered risk
      for malignancies as a function of insulin dosage, the duration of diabetes or
      insulin therapy, the quality of diabetes control or the prevalence of long-term
      complications of the disease.

PMID- 10929765
TI  - The Seoul Symposium of the Journal of Cancer Research and Clinical Oncology
      Regulation of aging and carcinogenesis.

PMID- 10929766
TI  - Skin nerve fibres and their contacts with mast cells in patients with
      palmoplantar pustulosis.
AB  - Patients with palmoplantar pustulosis (PPP) frequently report that stress worsens
      their condition. A study was therefore made of the distribution and number of
      nerve fibres positive for protein gene product (PGP) 9.5 (a general nerve marker)
      and nerve fibres with substance P- and calcitonin gene-related peptide-like
      immunoreactivity in involved skin from patients with PPP and in skin from healthy
      controls. The number of mast cells in the papillary dermis was larger (P =
      0.0003) in lesional palmar PPP skin than in control skin, and the number of
      contacts between mast cells and nerve fibres was significantly larger (P = 0.02)
      in PPP skin than in control skin. Image analysis of the nerve fibres around the
      sweat glands showed that the positively stained area as a percentage of the total
      area of the sweat gland (coil + surrounding nerves) was significantly lower in
      PPP skin (P = 0.0006). Furthermore, the nerves seemed to be fragmented.
      Neutrophils within and below the pustules and in the papillary dermis showed
      positive substance P staining. The increased number of contacts between nerves
      and mast cells in PPP skin and the intense substance P-like immunoreactivity of
      the neutrophils indicate that neuromediation may influence the inflammation in
      PPP, whereas the destruction of the nerve fibres around the sweat glands might be
      a result of the inflammation.

PMID- 10929767
TI  - Human papillomavirus in venous ulcers with and without squamous cell carcinoma.
AB  - Malignant transformation of chronic wounds is a well-known, albeit rare,
      phenomenon. We examined archival paraffin blocks of samples of squamous cell
      carcinoma (SCC) in chronic venous leg ulcers previously taken from 23 patients
      and of chronic noncancerous venous leg ulcers from 35 patients for the presence
      of human papillomavirus (HPV) DNA. The methods used were the polymerase chain
      reaction (PCR) with GP05+/06+ (mucosal) and nested PCR with CP65/70 and CP66/69
      (EV-associated) primers. A subsequent nonradioactive Southern blot hybridization
      was used to confirm the specificity of the PCR. With PCR three samples were
      positive on the gel, and with Southern blotting, a further seven samples were
      positive, to give a total of ten samples. All of the positive samples were from
      the noncancerous ulcers and with the primers GP05+/06+. HPV infection is probably
      not the carcinogen responsible for the malignant transformation of venous leg
      ulcers. The difference in positivity between the ulcers and the SCCs was
      statistically significant (P = 0.01) and raises the question as to whether HPV
      positive cells are eliminated in the interaction between the SCC and the immune
      system. Further studies on the carcinogenic effects of chronic proliferation and
      the role of HPV infection therein, are needed.

PMID- 10929768
TI  - Adamantiades-Behcet's disease: interleukin-8 is increased in serum of patients
      with active oral and neurological manifestations and is secreted by small vessel
      endothelial cells.
AB  - The serum levels of several cytokines were determined in 94 patients with
      Adamantiades-Behcet's disease (ABD), aged 36.1+/-11.0 years, during the active
      stage (n = 75) and the inactive stage (n = 19) of the disease. A group of 75
      healthy individuals matched for age and sex served as controls. Cytokine levels
      were determined using commercially available ELISA kits. Of the 75 patients with
      active disease and 19 with inactive disease, 38 (51%) and 4 (21%), respectively,
      and 23 healthy controls (31%) were found to have detectable levels of interleukin
      8 (IL-8) in their serum (P < 0.05). Also, increased IL-8 serum levels were found
      in patients with active disease (median 12 pg/ml, P = 0.010) compared to patients
      with inactive disease (< or = 10 pg/ml) and to healthy controls (< or = 10
      pg/ml). In particular, patients with oral aphthous ulcers (n = 51, 34 pg/ml) and
      neurological features (n = 4, 71 pg/ml) exhibited increased IL-8 levels. In
      contrast, there was no correlation between disease activity and the serum levels
      of IL-1alpha, IL-1beta, tumor necrosis factor alpha (TNF-alpha), soluble
      intercellular adhesion molecule-1 or basic fibroblast growth factor (bFGF). In a
      second set of experiments, the involvement of dermal microvascular endothelial
      cells in IL-8 secretion was investigated. Immortalized human dermal microvascular
      endothelial cells (HMEC-1 cells) were maintained for 4 h in vitro with serum from
      18 ABD patients or with IL-1beta, a known stimulator of IL-8 synthesis, TNF-alpha
      or their combination at five- to tenfold higher concentrations than those found
      in the serum of ABD patients. Increased IL-8 secretion was found after incubation
      with ABD patients' serum (median 20 pg/ml), but IL-1beta, TNF-alpha and IL-1beta
      + TNF-alpha failed to induce IL-8 secretion by HMEC-1 cells (< or = 1-1.2 pg/ml)
      in biologically relevant concentrations. Our study showed increased IL-8 serum
      levels in ABD patients with active oral and neurological manifestations. Human
      microvascular endothelial cells may, at least partially, be responsible for the
      enhanced IL-8 secretion in the active stage of the disease.

PMID- 10929769
TI  - Nickel-induced cytokine production from mononuclear cells in nickel-sensitive
      individuals and controls. Cytokine profiles in nickel-sensitive individuals with
      nickel allergy-related hand eczema before and after nickel challenge.
AB  - Exposure to nickel is a major cause of allergic contact dermatitis which is
      considered to be an inflammatory response induced by antigen-specific T cells.
      Here we describe the in vitro analysis of the nickel-specific T-cell-derived
      cytokine response of peripheral blood mononuclear cells from 35 nickel-allergic
      and 30 non-nickel-allergic individuals. Peripheral blood mononuclear cells were
      stimulated with 10(-4) and 10(-5) mol/l NiSO4 for 6 days and then additionally
      with ionomycin and phorbol myristate acetate for 24 h. Culture supernatants were
      analysed for interleukin-4 (IL-4), IL-5, interferon-gamma (IFN-gamma) and tumour
      necrosis factor-alpha (TNF-alpha) by quantitative ELISA. The analysis showed that
      the synthesis of IL-4 and IL-5 but not of IFN-gamma or TNF-alpha was
      significantly higher in the nickel-allergic individuals. The finding of
      preferential synthesis of Th2 cytokines was somewhat of a surprise, since
      previous studies have suggested a Th1 response in nickel-mediated allergic
      contact dermatitis. Subsequently, the nickel-allergic individuals were randomized
      to experimental exposure to nickel or vehicle in a double-blind design. A daily
      10-min exposure of one finger to 10 ppm nickel solution for 1 week followed by
      100 ppm for an additional week evoked a clinical response of hand eczema in the
      nickel-exposed group. Blood samples were drawn on days 7 and 14 after the start
      of this exposure to occupationally relevant concentrations of nickel. No
      statistically significant differences were observed in the nickel-induced in
      vitro cytokine response during the exposure period. Our results indicate the
      possibility that IL-4 and IL-5 are involved in the pathogenesis of nickel
      mediated contact dermatitis.

PMID- 10929770
TI  - Expression of lung resistance protein in epithelioid sarcoma in vitro and in
      vivo.
AB  - The incidence of epithelioid sarcoma among patients with malignant soft tissue
      tumors is small, but the rates of recurrence and metastasis of this type of
      sarcoma are high. To date, effective chemotherapy for advanced epithelioid
      sarcoma has not been established and, furthermore, epithelioid sarcoma is known
      to exhibit multidrug resistance (MDR). The chemosensitivities to anticancer
      agents of two cell lines established from epithelioid sarcoma were examined in
      this study. The results showed that the ES-OMC-MN and SFT-8606 cell lines were
      resistant to vincristine (IC50 1190 nM and 872 nM, respectively) and Adriamycin
      (IC50 921 nM and 650 nM, respectively), but sensitive to actinomycin D (IC50 < 10
      nM). P-glycoprotein (p-Gp) and MDR-associated protein (MRP) were not expressed in
      these cell lines, but a high expression level of lung resistance protein (LRP)
      was observed. The original tumor tissues from which the two cell lines were
      established were also found to be LRP-positive but not to express p-Gp or MRP.
      Their chemosensitivities to Adriamycin were not significantly altered in the
      presence of 2.5 microg/ml anti-LRP antibody (LRP-56), but the IC50 of vincristine
      was much less (IC50 128 nM and 27 nM, respectively) than that for an untreated
      cell line. It is thus suggested that the vincristine resistance in the two cell
      lines is LRP-mediated. Since cyclosporin A, known to be a modifier of p-Gp, also
      induced reversal of vincristine resistance in the ES-OMC-MN and SFT-8606 cell
      lines (IC50 6.2 nM and 17 nM, respectively), it is suggested that cyclosporin A
      acts as a modifier of MDR mediated by LRP.

PMID- 10929771
TI  - Electron microscopic DOPA reaction test for oculocutaneous albinism.
AB  - Oculocutaneous albinism (OCA) is an autosomal recessive disorder in which the
      biosynthesis of melanin is reduced or absent in skin, hair and eyes. Tyrosinase
      related OCA (OCA1) is caused by mutations in the tyrosinase gene. Tyrosinase
      negative OCA (OCA1A) is the most severe phenotype in which tyrosinase catalytic
      activity is completely lost, resulting in no mature melanin pigment. Yellow OCA
      (OCA1B) varies from very little pigment associated with whitish-blond hair to
      nearly normal pigment with dark-blond hair and skin. We determined the tyrosinase
      activity in melanocytes by the electron microscopic dihydroxyphenylalanine (EM
      DOPA) reaction test using skin samples and analyzed tyrosinase gene mutations in
      nine Japanese patients with OCA. In 18 alleles of nine patients, the OCA1A
      associated mutations, P310insC, R77Q and R278X, were found in seven, three and
      one alleles, respectively. Five patients who had these mutations in both alleles
      showed white hair, blue eyes and white skin and demonstrated no tyrosinase
      activity by the EM-DOPA reaction test. Three patients who had no tyrosinase gene
      mutation showed tyrosinase activity and heterogeneous clinical features. One
      patient in whom only an R77Q OCA1A mutation was found in one allele demonstrated
      a reduced tyrosinase activity, indicating OCA1B. This patient had white hair at
      birth, but it had turned blond by the age of 1 year. These results indicate that
      the EM-DOPA reaction test provides clear information on the status of tyrosinase
      activity which is essential for the identification of the disease subtype which
      in turn is important for the prognosis of patients with OCA.

PMID- 10929772
TI  - In vitro determination of sunscreen immune protection factors.
AB  - The present study was aimed at determining immune protection factors (IPFs) for
      sunscreens. Human skin explants from donors of phototype II-III were treated, or
      not, with sunscreens with increasing sun protection factors (SPF 4, 8, 15 and
      30), or their respective vehicles. Explants were submitted, or not, to increasing
      doses of UVB irradiation (312 nm). After an 18-h incubation at 37 degrees C,
      epidermal cells were recovered through trypsinization and tested in a mixed
      epidermal cell/T lymphocyte reaction. The UVB dose providing 50%
      immunosuppression (D50%) was determined graphically. We first demonstrated a
      large difference in the individual response to UVB, as assessed by the D50% in
      the absence of any topical treatment (mean 1615+/-839 J/m2 from 14 experiments
      with values ranging from 500 to 3200 J/m2). For all the tested sunscreens, the
      D50% values were significantly higher than those obtained without sunscreens or
      with their respective vehicles (P < 0.01), thus demonstrating their
      immunoprotective effect. IPFs were determined as the ratio of the D50% in the
      presence of sunscreen to that with vehicle alone. Although they displayed
      important individual variations, IPFs ranked according to the sunscreen SPFs.

PMID- 10929773
TI  - Ultraviolet B radiation downregulates inducible nitric oxide synthase expression
      induced by interferon-gamma or tumor necrosis factor-alpha in murine keratinocyte
      Pam 212 cells.
AB  - Ultraviolet radiation causes inflammation characterized by erythema and swelling,
      but also exhibits antiinflammatory effects which have led to the use of
      ultraviolet B radiation (UVBR) and psoralen plus ultraviolet A (PUVA) in the
      treatment of psoriasis, chronic severe atopic dermatitis and uremic pruritus. In
      inflammatory dermatoses, a pathogenic role of nitric oxide (NO) derived from
      inducible nitric oxide synthase (iNOS) has been suggested. To elucidate how UVBR
      regulates iNOS expression in skin under inflammatory conditions, we investigated
      the effect of UVBR on NO production and iNOS expression in cultured murine
      keratinocyte Pam 212 cells stimulated with interferon-gamma (IFN-gamma) or tumor
      necrosis factor-alpha (TNF-alpha). Low doses of UVBR significantly suppressed IFN
      gamma- or TNF-alpha-induced NO production. UVBR also downregulated IFN-gamma- or
      TNF-alpha-induced iNOS expression at both the mRNA level and the protein level.
      These findings suggest the possibility that the down-regulatory effect of UVBR on
      IFN-gamma- or TNF-alpha-induced iNOS expression may, in part, explain the
      antiinflammatory and therapeutic properties of UVBR in inflammatory dermatoses.

PMID- 10929774
TI  - High-performance liquid chromatography analysis of porphyrins in
      Propionibacterium acnes.

PMID- 10929775
TI  - Detection of viable myocardium by dobutamine stress tagging magnetic resonance
      imaging with three-dimensional analysis by automatic trace method.
AB  - The present study attempted to detect the viability of myocardium by quantitative
      automatic 3-dimensional analysis of the improvement of regional wall motion using
      an magnetic resonance imaging (MRI) tagging method. Twenty-two subjects with
      ischemic heart disease who had abnormal wall motion on echocardiography at rest
      were enrolled. All patients underwent dobutamine stress echocardiography (DSE),
      coronary arteriography and left ventriculography. The results were compared with
      those of 7 normal volunteers. MRI studies were done with myocardial tagging using
      the spatial modulation of magnetization technique. Automatic tracing with an
      original program was performed, and wall motion was compared before and during
      dobutamine infusion. The evaluation of myocardial viability with MRI and
      echocardiography had similar results in 19 (86.4%) of the 22 patients; 20 were
      studied by positron emission tomography or thallium-201 single photon emission
      computed tomography for myocardial viability, or studied for improvement of wall
      motion following coronary intervention. The sensitivity of dobutamine stress MRI
      (DSMRI) with tagging was 75.9% whereas that of DSE was 65.5%. The specificity of
      DSMRI was 85.7% (6/7) and that of DSE was 100% (7/7). The accuracy of DSMRI was
      77.8% (28/36) and that of DSE 72.2% (26/36). DSMRI was shown to be superior to
      DSE in terms of evaluation of myocardial viability.

PMID- 10929776
TI  - Pericardial fluid from patients with ischemic heart disease accelerates the
      growth of human vascular smooth muscle cells.
AB  - The strong association between severe coronary stenosis and collateral growth
      continues to be a paradigm in this field of investigation. The present study was
      based on the hypothesis that angiogenic growth factors are produced by ischemic
      cardiac tissue, are diffusible and more concentrated in pericardial fluid, and
      accelerate the growth of vascular smooth muscle cells (VSMC). Pericardial fluid
      from 17 patients with stable or unstable angina or acute myocardial infarction
      (group A) and from 10 patients with nonischemic heart disease (group B) were
      collected at the time of open heart surgery. Cultured human aortic VSMC were
      plated at the third passage at a density of 5x10(3)/100 microl and allowed to
      attach for 24 h. The 3-day growth assay was preceded by 72 h of growth arrest
      with 0.4% fetal calf serum (FCS). Growth was restarted by the addition of 90
      microl of medium containing 0.4% FCS, and 1O microl of each pericardial fluid.
      Cell counts on triplicate wells were performed using a dimethylthiazol (MTT)
      method on days 0 and 3. The effect of pericardial fluid on the growth of VSMC was
      evaluated as a ratio (R) of cell numbers on day 3 to those on day 0. The
      concentration of basic fibroblast growth factor (bFGF) in pericardial fluid was
      measured by an enzyme-linked immunosorbent assay. The concentration of bFGF in
      pericardial fluid of group A was 633+/-127 pg/ml, and significantly (p=0.003)
      higher than that of group B (86+/-23 pg/ml). R in group A was 2.29+/-0.18 and
      significantly (p=0.019) higher than that in group B (1.68+/-0.11). The level of
      bFGF positively correlated with R (p=0.009). These findings indicate that
      pericardial fluid from patients with ischemic heart disease contains some
      substances that mediate collateral development, and bFGF might be one of them.

PMID- 10929777
TI  - Cardiac arrhythmias and left ventricular hypertrophy in dipper and nondipper
      patients with essential hypertension.
AB  - To evaluate the behavior of cardiac arrhythmias in dipper and nondipper
      hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter
      electrocardiogram recording and echocardiographic studies were performed in 56
      untreated outpatients with essential hypertension. These patients were divided
      into 2 groups according to the presence (dipper, n=33) or absence (nondipper,
      n=23) of reduction of both systolic and diastolic blood pressure during nighttime
      by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and
      diastolic blood pressures did not differ between the 2 groups. Nondipper patients
      had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm;
      p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well
      as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05)
      and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as
      compared with dippers. In conclusion, nondipper hypertensive patients are likely
      to experience supraventricular and ventricular arrhythmias more frequently than
      dippers. A blunted nocturnal blood pressure fall may be involved in the
      appearance of cardiac arrhythmias in patients with essential hypertension.

PMID- 10929779
TI  - Standardized ejection fraction as a parameter of overall ventricular pump
      function.
AB  - To evaluate the pump function of the ventricle, a parameter which (i)
      incorporates systolic and diastolic function and (ii) separates the heart from
      preload and afterload is needed. This study utilized ejection fraction (EF),
      calculated from the end-systolic (ES) and end-diastolic (ED) pressure-volume
      relationship (PVR) using an arbitrary set of loading conditions. Ten isolated
      canine hearts with a balloon placed inside the left ventricle were used to
      determine the ESPVR and EDPVR. An end-diastolic volume (EDV) at a pressure of 15
      mmHg and an end-systolic volume (ESV) at 70 mmHg were obtained from the EDPVR and
      ESPVR, respectively. EF was calculated as (EDV-ESV)/EDV. With low-dose (8
      microg/min) and high-dose (40 microg/min) dobutamine infusion, the EF increased
      from 0.25+/-0.16 to 0.33+/-0.13 and 0.57+/-0.08 (p<0.01), respectively, in
      conjunction with increases in end-systolic elastance from 3.11+/-0.83 to 3.48+/
      1.08 and 5.38+/-1.91 mmHg/ml (p<0.01). It was thus concluded that because the
      estimation of EF separates the heart from preload and afterload, this method may
      facilitate comparing overall pump function of hearts beating under different
      loading conditions.

PMID- 10929778
TI  - Incidence of atrial flutter and atrial fibrillation in patients with implanted
      physiological pacemakers.
AB  - Atrial flutter (AF) is a troublesome arrhythmia for patients with an implanted
      pacemaker. Although it has recently become possible to eliminate AF by
      radiofrequency catheter ablation (RF-CA), the incidence of AF before and after
      pacemaker implantation has not been clarified. The present study was conducted
      with 123 consecutive patients (69.3+/-11.6 (SD) years old) implanted with
      pacemakers, excluding patients who had chronic atrial fibrillation (AFib) when
      the pacemaker was implanted; 69 patients with atrioventricular (AV) block and 54
      patients with sick sinus syndrome (including 29 patients with bradycardia
      tachycardia syndrome). All patients were implanted with physiological pacemakers.
      The follow-up period was 4.7+/-1.9 years. In 11 of the 123 patients (8.9%), AF
      was observed before pacemaker implantation and the incidence was significantly
      higher in patients with sick sinus syndrome than in those with AV block (16.7 vs
      2.9%, p<0.01). Nine of the 29 patients with bradycardia-tachycardia syndrome
      (31%) had AF. After physiological pacemaker implantation, AF recurred in 9 of the
      11 patients, and AF was newly observed in 1 patient. Thus, 10 of the 123 patients
      (8.1%) had AF after physiological pacemaker implantation. Recurrence of AF was
      not suppressed by physiological pacing. Thirty of the 123 patients had AFib
      before implantation of a pacemaker and its occurrence was reduced by
      physiological pacing (from 24.4% to 12.2%, p<0.05). The incidence of AFib in
      patients with AF was significantly higher than in those without AF (90.0 vs 5.3%,
      p<0.001). In conclusion, the recurrence of AF is not prevented by physiological
      pacing and is closely related to the occurrence of AFib. RF-CA should be
      considered in patients who have AF before pacemaker implantation.

PMID- 10929780
TI  - Pulse dispersion due to atrial fibrillation causes arterial thrombosis in a
      rabbit experimental model.
AB  - Thrombosis associated with atrial fibrillation (AF) is usually caused by a left
      atrial (LA) thrombus, but it is not always detected. The present study was based
      on the hypothesis that abnormalities in peripheral artery are responsible for the
      ischemic stroke associated with AF. Peripheral arterial coagulability was
      investigated in a rabbit experimental model in which AF was induced by high
      frequency stimulation of the right atrium, creating stenosis of the carotid
      artery together with endothelial damage. The rabbits were classified into 4
      groups: (i) sinus rhythm only (group 1), (ii) sinus rhythm after 6 h of pacing
      (group 2), (iii) short AF (continuous pacing for 5 min; group 3) and (iv) long AF
      (continuous pacing for 6 h: group 4). The carotid blood flow developed a typical
      pattern, called cyclic flow reductions (CFRs), the frequency of which (CFRF) was
      18.59+/-2.85 in AF (group 3+4) compared with 14.46+/-2.1 in sinus rhythm (group
      1+2) (p<0.0005). Among the groups with AF, correlation analysis showed an
      association between CFRF and pulse dispersion (p<0.02, r=0.58). This study
      suggests that the distinctive hemodynamic effects with AF, in particular pulse
      dispersion, substantively influence thrombus formation on injured vascular
      endothelium.

PMID- 10929781
TI  - Transcatheter occlusion of patent ductus arteriosus using a 0.052-inch coil-
      immediate results.
AB  - Coil occlusion of a patent ductus arteriosus (PDA) was attempted with a 0.052
      inch Gianturco coil. The patients' ages and body weights at occlusion ranged from
      5.8 to 19.7 (12.3+/-5.0, mean+/-SD) years and 18.9-99.1 (44.8+/-23.7) kg,
      respectively. Three types of 0.052-inch Gianturco coils with loop diameters (mm)
      and coil lengths (cm) of 6x8 (diameter x length), 8x8, or 8x10 were used. The
      delivery system was prepared as reported by Hays et al with slight modification.
      The minimal diameter and the Qp/Qs of the PDA ranged from 2.3 to 4.7 (3.4+/-0.7)
      mm, and 1.1-1.8 (1.5+/-0.3), respectively. There were 7 cases with type A PDA and
      3 with type B, and coils were successfully deployed in all. Complete occlusion in
      the catheter laboratory was achieved in 4 cases. A minor leak disappeared within
      24 h in 3 cases and at 3 months follow-up in 1 case. A tiny leak without a heart
      murmur persisted in 2 cases at 3 months' follow-up. No procedure-related
      complications occurred. This technique has significant advantages over previously
      reported techniques using a 0.038-inch coil for type B, or A PDA with a minimal
      diameter of 3-4 mm or more.

PMID- 10929782
TI  - Endothelial nitric oxide synthase gene mutation and human leukocyte antigen
      analyzed in three cases of familial vasospastic angina pectoris.
AB  - A 50-year-old woman with rest angina underwent cardiac catheterization; coronary
      angiography in the presence of acetylcholine revealed 99% coronary spasm of the
      proximal left anterior descending artery. The patient's 82-year-old mother was
      also admitted to hospital with rest angina. Her Holter electrocardiogram showed
      ST-segment elevation during the attack at rest and coronary angiography showed
      99% spasm of the right coronary artery and 90% spasm of the left coronary artery.
      Both women complained of chest pain during the spasm, which was accompanied by ST
      segment depression. The 62-year-old brother of the original patient was also
      found to have coronary spasm of the left coronary artery. Human leukocyte antigen
      was analyzed in the 2 women: A2, B51, CW1, DR8 and DQ1 were common factors. A
      Glu298Asp point mutation of the endothelial nitric oxide synthase gene was
      investigated in both parents, their 2 daughters and 2 sons, but was not detected
      in the 3 patients, and was detected only in the 90-year-old father who did not
      suffer from angina. Nor was the T-786-C mutation found in the 3 cases. Other
      causes of familial spasm need to be elucidated.

PMID- 10929783
TI  - Percutaneous cardiopulmonary support as a bridge to emergency operation--two
      surviving cases.
AB  - Two patients had percutaneous cardiopulmonary support (PCPS) used as a bridge to
      emergency surgery. A 66-year-old man admitted with profound cardiogenic shock
      underwent direct stenting under PCPS with the diagnosis of acute myocardial
      infarction of the left main trunk, with the intention of performing
      revascularization as soon as possible. Subsequently, double coronary artery
      bypass grafting was successfully accomplished. A 69-year-old woman, admitted with
      acute heart failure due to critical aortic stenosis, manifested cardiogenic shock
      while undergoing catheterization. PCPS was immediately instituted until the acute
      deterioration of her hemodynamic state could be reversed, and was continued
      uneventfully till aortic valve replacement was performed. These results suggest
      that the current PCPS system is an effective response to acute circulatory
      collapse and will contributed to the improved survival of patients.

PMID- 10929784
TI  - Global myocardial ischemia as a complication of an acute type A aortic dissection
      -rapid diagnosis of a case by transesophageal echocardiography.
AB  - A 36-year-old female was admitted for severe chest pain followed by profound
      shock. Electrocardiography showed severe ST segment depression (0.5-0.7 mV) in
      all leads except aVR and aVL. Echocardiography revealed an intimal flap in the
      ascending aorta and coexisting grade 3 aortic regurgitation. She was immediately
      intubated and transferred to the intensive care unit. Transesophageal
      echocardiography (TEE) demonstrated an intimal tear at 2 cm above the sinotubular
      junction, and the ostium of the left main trunk was oppressed by the intimal flap
      during diastole. Emergency graft replacement of the ascending aorta and aortic
      hemiarch concomitant with aortic valve resuspension was performed successfully.
      The ECG changes reversed to normal immediately after the operation. The patient
      was extubated 2 days postoperatively and discharged from the hospital 14 days
      postoperatively. TEE is useful for the rapid evaluation of coronary malperfusion
      as a complication of acute aortic dissection, especially in patients with
      hemodynamic instability.

PMID- 10929785
TI  - Serum atrial natriuretic peptide concentration is a useful predictor of atrial
      standstill in patients with heart failure.
AB  - Two cases of atrial standstill are presented, one with cardiac amyloidosis, the
      other with idiopathic dilated cardiomyopathy. The plasma atrial natriuretic
      peptide (ANP) concentration was normal to slightly elevated in both patients,
      despite a marked elevation of the plasma brain natriuretic peptide (BNP)
      concentration. In the patient with amyloidosis (ANP: 170 pg/ml, BNP: 1220 pg/ml),
      a dual chamber pacemaker was successfully implanted for the treatment of sinus
      arrest. However, loss of atrial capture occurred 1 month later. In the patient
      with dilated cardiomyopathy (ANP: 47 pg/ml, BNP: 422 pg/ml), an
      electrophysiologic study confirmed persistent atrial standstill and failure to
      pace from either the right atrium or the coronary sinus. The hypothesis is that
      the attenuated increase in plasma ANP concentration relative to the increase in
      the BNP concentration may be a sensitive and useful marker to confirm atrial
      standstill in the setting of congestive heart failure.

PMID- 10929786
TI  - Renovascular hypertension observed in a patient with antiphospholipid-antibody
      syndrome.
AB  - The antiphospholipid-antibody syndrome is associated with an increased incidence
      of arterial and venous thrombosis. Although renal infarction has been observed in
      these patients, stenotic lesions of the renal artery associated with the
      antiphospholipid-antibody syndrome have not been reported. A 47-year-old male
      with a history of hypertension for 7 years developed blurred vision secondary to
      thrombotic occlusion of the central retinal artery. Laboratory and radiologic
      examinations revealed renal dysfunction, a positive anticardiolipin antibody, and
      narrowing of the right renal artery. Successful percutaneous transluminal renal
      artery angioplasty resulted in normalization of the blood pressure and recovery
      of renal function.

PMID- 10929787
TI  - Left cervical aortic arch with aortic coarctation and saccular aneurysm.
AB  - Cervical aortic arch is a very rare malformation and is occasionally accompanied
      by other cardiovascular anomalies. A 48-year-old male patient had a left cervical
      aortic arch with aortic coarctation and saccular aneurysm distal to the coarcted
      segment. The major clinical manifestations were upper body hypertension with a 50
      mmHg discrepancy between the upper and lower limbs and a loud continuous murmur
      in the upper chest and back. Magnetic resonance angiography successfully depicted
      the anomalous aorta, and the aortic coarctation and aneurysm were surgically
      resected and the thoracic aorta was reconstructed. The discrepancy in blood
      pressure diminished after the operation, but antihypertensive medication was
      continued to satisfactorily control the hypertension.

PMID- 10929789
TI  - Qualitative differences in manic symptoms during mixed versus pure mania.
AB  - Previous studies have compared demographic and clinical-outcome features of
      bipolar patients with mixed or pure mania. However, little is known about the
      potential differences in the nature and extent of manic symptoms in mania either
      with or without an accompanying depression. This study examined DSM-III-R manic
      symptoms in a cohort of 183 bipolar I inpatients hospitalized for mixed mania
      (diagnosed by broad or narrow criteria) or pure manic episodes. Inpatient charts
      were reviewed to determine the presence of individual affective symptoms. The
      results indicate that clinicians were more likely to diagnose a pure mania from
      the beginning to end of an episode than to diagnose a mixed mania from its
      beginning to end. Mixed-manic patients had significantly fewer manic symptoms
      than pure manic patients. Grandiosity, euphoria, pressured speech, and a
      decreased need for sleep were more prevalent during pure versus mixed mania.
      Grandiosity and a diminished need for sleep were especially notable during pure
      mania compared with mixed mania as defined by narrow criteria for mixed states.
      The observed differences in manic symptom profiles between mixed and pure mania
      may aid in the clinical assessment of dysphoric states among bipolar patients.
      The data also lend support to the use of broad diagnostic criteria for defining
      mixed mania as an entity phenomenologically distinct from pure mania.

PMID- 10929788
TI  - Personality disorders and traits in patients with body dysmorphic disorder.
AB  - Individuals with body dysmorphic disorder (BDD) have been postulated to have
      schizoid, narcissistic, and obsessional personality traits and to be sensitive,
      introverted, perfectionistic, and insecure. However, data on personality traits
      and disorders in BDD are limited. This study assessed 148 subjects with BDD, 26
      of whom participated in a fluvoxamine treatment study; 74 subjects were assessed
      for personality disorders with the Structured Clinical Interview for DSMIII-R
      Personality Disorders (SCID-II), 100 subjects completed the NEO-Five Factor
      Inventory (NEO-FFI), and 51 subjects completed the Rathus Assertiveness Scale.
      Forty-two subjects (57%) had one or more personality disorders, with avoidant
      personality disorder (43%) being most common, followed by dependent (15%),
      obsessive-compulsive (14%), and paranoid (14%) personality disorders. On the NEO
      FFI, the mean scores were in the very high range for neuroticism, the low range
      for extraversion and conscientiousness, the low-average range for agreeableness,
      and the average range for openness to experience. On the Rathus Assertiveness
      Scale, the mean score was -17.1 +/- 32.0 for women and -17.0 +/- 32.3 for men.
      Among fluvoxamine responders, the number of personality disorders significantly
      decreased between the study baseline and endpoint. These findings suggest that
      the rate of personality disorders in BDD is relatively high, with avoidant
      personality disorder being most common. The high neuroticism scores and low
      extraversion scores are consistent with this finding.

PMID- 10929790
TI  - Clinical characteristics of mania, mixed mania, and bipolar depression with
      psychotic features.
AB  - This study investigated a series of clinical characteristics, including the level
      of insight into illness and axis I comorbidity, in 125 patients with bipolar
      disorder with psychotic features categorized in three groups: 62 patients with
      mania, 28 patients with mixed mania, and 35 patients with depression. All
      patients were hospitalized and were assessed in the week preceding discharge. The
      three groups did not differ in the severity of psychopathology as assessed by the
      Brief Psychiatric Rating Scale (BPRS). The mania group had a lower level of
      insight into the social consequences of illness than the other two groups, and
      compared with the group with depression, they had a lower level of insight of
      poor attention and of poor social judgment. As to axis I comorbidity, obsessive
      compulsive disorder was found to be significantly more frequent in depression
      than in mania. Patients with depression more frequently reported a history of
      suicidality than those with mania, whereas they did not significantly differ from
      patients with mixed mania. Our results suggest that mixed mania as assessed at
      the time of the patient's discharge differs from mania and from depression with
      respect to a limited number of features among those examined. However, the
      overall level of insight into illness significantly discriminated mixed mania
      from mania, but not from depression.

PMID- 10929791
TI  - Neuroleptic exposure in bipolar outpatients in a research setting.
AB  - The study purpose was to determine the extent of neuroleptic exposure in bipolar
      outpatients maintained on mood-stabilizing medications and any clinical
      correlates associated with this exposure. Data on medication and severity of
      illness were gathered from the records (prospective and retrospective) of 70
      bipolar patients involved in outpatient research studies at the National
      Institute of Mental Health (NIMH). The percentage of patients requiring
      neuroleptic treatment, percentage of time on neuroleptics during the period of
      observation, total dose of neuroleptics in chlorpromazine (CPZ) equivalency, and
      number of neuroleptic trials were among the variables calculated. Regression
      analyses and analyses of variance (ANOVAs) were performed to assess the
      relationships between neuroleptic exposure and clinical course. Forty-five
      patients (64.3%) had a neuroleptic trial during the prospective study. Subjects
      exposed to neuroleptics spent, on average, 15.4% (median, 6.0%) of the time in
      study on neuroleptic treatment, and were administered, on average, a total of
      11,770.5 mg (median, 1,621.9 mg) of neuroleptics (in CPZ equivalency) per year in
      the prospective study. As expected, bipolar I compared with bipolar II patients
      had significantly higher neuroleptic exposure by a number of measures. The number
      of hospitalizations for mania prior to study entry was associated with greater
      prospective neuroleptic use during the study. Despite maintenance treatment with
      one or more moodstabilizing agents, we found a relatively high need for
      adjunctive neuroleptic medication even in this sample of high-functioning bipolar
      outpatients. These results highlight the need for the study of alternatives, as
      well as more effective primary mood-stabilizing agents.

PMID- 10929792
TI  - Generalized anxiety disorder versus panic disorder: participation in controlled
      efficacy trials.
AB  - Seventy-one patients with panic disorder (PD) and 46 patients with generalized
      anxiety disorder (GAD) were studied in relation to their behavior before, during,
      and after participation in two contemporaneous and procedurally similar double
      blind drug efficacy trials. The two groups were administered a battery of
      assessments aimed at comparing them on the nature and intensity of various
      symptom domains, social and work-related disability, personality, life events,
      and previous treatments. The results yielded few significant differences that
      were not due to definitional factors, most notably a more prevalent history of
      depression and treatment for depression in the GAD group and a higher rate of
      pharmacological treatment in the PD group. On the other hand, the two groups
      behaved in a comparable way in the screening, experimental, and postexperimental
      phases of the trials. The findings are in support of more similarities than
      differences between the groups. In addition, the comparable behavior of the two
      groups throughout the three phases of the trial suggests that differential
      pretreatment attrition and compliance with placebo-controlled trials may not
      present major confounding problems in comparative treatment effectiveness studies
      between GAD and PD diagnostic groups.

PMID- 10929793
TI  - Process-outcome analysis in computer-aided treatment of obsessive-compulsive
      disorder.
AB  - The study purpose was to examine dose-response relationships between behavior on
      a computer-delivered treatment program and outcome in obsessive-compulsive
      disorder (OCD), and to report the use of human-computer interactions (HCIs) as a
      process measure in psychotherapy research. Thirteen OCD patients completed three
      45-minute sessions at weekly intervals on an interactive computer program which
      provided vicarious exposure and response prevention for OCD. The scenario modeled
      exposure to dirt for the treatment of a hand-washing ritual. HCIs were recorded
      and analyzed to provide a detailed description of the behavioral strategies used.
      The relationship between subject characteristics, process measures, and outcome
      was examined. Across the three computer treatment sessions, all subjects showed a
      marked increase in vicarious exposure behavior, that is, enacting a hand-dirtying
      behavior sequence on the interactive computer program. Some subjects enacted hand
      washing, although this decreased across sessions. A higher amount of vicarious
      hand-dirtying behavior predicted symptom reduction on the Padua Inventory (PI).
      Higher National Adult Reading Test (NART) scores, an intelligence measure,
      predicted more enactments of hand-dirtying behavior, but the relationship between
      hand-dirtying and outcome remained significant after controlling for NART scores.
      We conclude that HCIs are a novel and objective process measure that may aid in
      clarifying specific treatment factors. The relationship between hand-dirtying and
      outcome suggests a likely increased benefit from higher treatment dosages.

PMID- 10929794
TI  - Gender differences in social and interpersonal features and personality disorders
      among Japanese patients with obsessive-compulsive disorder.
AB  - This study sought to elucidate the differential effect of gender on clinical
      features in 40 males and 54 females who met both DSM-III-R and DSM-IV criteria
      for obsessive-compulsive disorder (OCD). Males had a lower rate of marriage, and
      a higher rate of major impairment in social or occupational functioning, whereas
      females were significantly more likely to involve others in their OCD symptoms,
      such as reassurance-seeking. Although no significant differences were detected in
      the distribution of OCD symptoms, cluster A personality disorders (PDs),
      especially schizotypal PD, were more frequently diagnosed in males, and
      borderline and dependent PDs tended to be more prevalent in females. Thus, gender
      differences in OCD subjects were prominently observed in social or interpersonal
      features, which might be consistent with the differential PD pathology between
      males and females.

PMID- 10929795
TI  - Adult gender identity disorder can remit.
AB  - A 4-year remission in a case of gender identity disorder (GID in DSM-IV,
      previously termed transsexualism) plus obsessive-compulsive disorder (OCD)
      prompted a search for further similar cases. Reports were reviewed for apparent
      remissions in adult GID. GID and paraphilias may wax and wane. This fluctuation
      can be in tandem with that of comorbid psychopathology or in response to sexual
      and other life events. Remission has been documented at up to 10 years. If
      evaluated over many years, GIDs and paraphilias can be less fixed than is often
      thought. The frequency of permanent remission may be underestimated, as such
      subjects may not consult clinicians. Implications for the clinician are that such
      subjects require a long trial period of cross-gender living prior to any surgical
      interventions.

PMID- 10929796
TI  - Personality and substance use disorders as predictors of criminality.
AB  - The study objective was to evaluate the relationship between a personality
      disorder (PD) diagnosis and criminal behavior among drug- and alcohol-dependent
      patients both retrospectively and prospectively. We examined 1-year pretreatment
      and 1-year post-treatment crime rates among 370 drug- and/or alcohol-dependent
      patients. Hierarchical logistic regression was used to examine the predictive
      value of DSM-III-R PD diagnoses after controlling for demographic features and
      type and severity of substance dependence. Patients with a diagnosis of
      antisocial PD (ASPD) were more likely to report having committed a variety of
      crimes, including violent crimes, during the pretreatment period. Individuals
      with more PD diagnoses or a diagnosis of borderline PD (BPD) or schizoid PD also
      reported a greater number of pretreatment violent crimes. In addition, the number
      of PD diagnoses was correlated with the number of crimes against property. During
      the pretreatment period, significant interactions were also found between PD
      measures and substance use in relation to both property crimes and violation of
      parole or probation. During the posttreatment period, a diagnosis of BPD
      predicted the commission of violent crimes. In contrast, a cluster A PD predicted
      a lower frequency of crimes against property. ASPD did not predict criminality
      during the 1-year follow-up period. In conclusion, a PD diagnosis, particularly
      ASPD, was associated with a variety of criminal behaviors during the 1-year
      period preceding substance abuse treatment. Following treatment, PD diagnosis had
      limited value in the prediction of criminal behavior. Possible explanations for
      these findings are discussed.

PMID- 10929797
TI  - The impact of neuroleptic dosage and extrapyramidal side effects on schizophrenic
      basic symptoms.
AB  - The impact of neuroleptic medication and extrapyramidal symptoms on abnormal
      subjective experiences in schizophrenia, also termed basic symptoms, as assessed
      with the Frankfurt Complaint Questionnaire (FCQ) was investigated in 40
      schizophrenic patients medicated with conventional neuroleptics. Basic symptoms
      are thought to reflect the subjective side of schizophrenic vulnerability and to
      underlie schizophrenic symptomatology. It was expected that basic symptoms would
      inversely correlate with chlorpromazine equivalents, since neuroleptics not only
      improve acute schizophrenic symptoms but also have prophylactic properties.
      However, a significant positive correlation with neuroleptic dosage and
      extrapyramidal symptoms emerged, suggesting that basic symptoms as
      operationalized in the FCQ partly reflect neuroleptic-induced deficits. The
      results remained unchanged when global psychopathology was controlled for. In
      line with previous research, basic symptoms correlated with thought disorder but
      not with positive symptoms. However, when the effects of neuroleptic-induced
      disturbances were controlled for, thought disorder also insignificantly
      correlated with basic symptoms. Our findings confirm previous results that
      question the construct validity of the FCQ. Moreover, the need to control for
      confounding variables (such as medication) is emphasized by comparing different
      psychiatric groups.

PMID- 10929798
TI  - Changes in psychological symptoms during the adjustment of recent immigrants.
AB  - In the present study, we sought to compare the number, severity, and frequency of
      psychological symptoms and the intensity of perceived stressors among immigrants
      with previously identified positive, negative, or normal patterns of distress. We
      evaluated 199 recent immigrants from the former Soviet Union to Israel using the
      Talbieh Brief Distress Inventory (TBDI) and the Perceived Immigration-Related
      Stressors Scale (PIRSS) with a 1-year follow-up period. As predicted, the number,
      severity, and frequency of psychological symptoms and the intensity of perceived
      stress factors vary among immigrants showing different distress patterns. A
      negative pattern was associated with an increase in the total number, severity,
      and frequency of distress-related symptoms and persisting cultural-related stress
      over time. A positive pattern was associated with a reduction in the overall
      number and severity of symptoms, as well as a decline in the frequency of
      distress-free symptoms and the intensity of all but informational-related
      stressors. A normal pattern was characterized by the reduction of distress
      symptoms within a normal range along with material- and health-related stresses.
      Our findings confirm the validity of the suggested classification for different
      patterns of distress and its usefulness in establishing the prognosis for the
      adjustment of immigrants.

PMID- 10929799
TI  - Comparing Personality Diagnostic questionnaire-4+ with Longitudinal, Expert, All
      Data (LEAD) standard diagnoses in a sample with a high prevalence of axis I and
      axis II disorders.
AB  - A comparison between the Personality Diagnostic Questionnaire-4+ (PDQ-4+) and
      Longitudinal, Expert, All Data (LEAD) standard diagnoses was made in a sample of
      100 patients with a high prevalence of both axis I and axis II disorders. The
      internal consistency was considered acceptable (alpha >.70) for 3 of 12 PDQ-4+
      scales. Diagnostic agreement between the assessment methods was poor for specific
      personality disorders (PDs). The PDQ-4+ gave many false-positive diagnoses.
      Changing the diagnostic thresholds only marginally increased the agreement
      between methods or the diagnostic efficiency of the PDQ-4+. Multiple regression
      analyses showed that the discrepancies between the methods were strongly
      associated with the current level of perceived symptoms (SCL-90-R).

PMID- 10929801
TI  - Analyzing sialic acids using high-performance anion-exchange chromatography with
      pulsed amperometric detection.

PMID- 10929800
TI  - Medical students' evolving perspectives on their personal health care: clinical
      and educational implications of a longitudinal study.
AB  - The mental and physical health care issues of medical students are increasingly
      recognized as both prevalent and complex. Emotional distress, symptoms of mental
      illness, and maladaptive substance use are widespread and may often be driven by
      training-related stressors. The data suggest that nearly all medical students
      identify physical health concerns as well. The care of medical students as
      patients is complex because of problems associated with the stigma of various
      illnesses and the dual role of trainee and patient in medical school. A written
      confidential survey assessed students longitudinally near the end of their first
      and third years of training regarding their perceived health care needs, health
      concerns, attitudes toward care, access to services, and care-seeking practices
      (161 items). A subset of students (n = 33) were reassessed 1 month after the
      second survey to measure reliability. McNemar's chi-square (chi2) tests, repeated
      measures multivariate analysis of variance (MANOVA), and K and Pearson
      correlations were used to evaluate outcomes. Almost all students reported health
      care needs during both training phases, and their mental and physical health
      concerns were stable over time. However, the preference for obtaining health care
      at a site other than their training institution and concerns about
      confidentiality increased, although students were marginally more likely to
      obtain care at their medical school during clinical versus preclinical training.
      The students' tendency to seek informal care from colleagues remained consistent,
      as did their high level of concern about professional jeopardy relating to
      personal health issues. Their tendency to accept the dual patient-student role
      depended on the particular health care issue; they expressed a strong tendency to
      protect other students' confidentiality, even in cases of potential significant
      impairment. Responses were reliable across a 1-month retest interval. We conclude
      that medical students' perspectives on their mental and physical health care
      across the transition from preclinical to clinical training reveal the importance
      of pursuing, not neglecting, a number of clinical and educational initiatives.
      Through their specialized expertise, psychiatrists may help to ensure sound
      mental and physical health care for the more than 69,000 medical students in
      training in this country.

PMID- 10929802
TI  - Derivatization strategies for preparing N-glycan probes.

PMID- 10929803
TI  - High-sensitivity and high-resolution methods for glycoprotein analysis.

PMID- 10929804
TI  - Detection and measurement of a single blood cell surface antigen by thermal lens
      microscopy.
AB  - A highly sensitive method for detection of antigens on the surface of a single
      blood cell using thermal lens microscopy is described. Colloidal gold, coated
      with antibody, was used to stain membrane antigens of leukocytes. Human leukocyte
      antigens on the lymphocytes and mononuclear leukocytes were observed by new
      thermal lens microscopy, which involves spectrometry using a laser-induced
      thermal-lens effect. Antigens of HLA-A, -B, and -C loci on the lymphocytes were
      identified and quantitated using a single cell. The image of HLA-A, -B, and -C
      antigen distribution on a mononuclear leukocyte was obtained. Our laser
      microscope, newly devised for measuring convex surface cells, is a powerful
      analytical tool for detecting and quantitating localized antigens in a single
      cell and/or cell-surface-associated molecules.

PMID- 10929805
TI  - Development of a fluorescence immunoassay for measurement of paclitaxel in human
      plasma.
AB  - A new fluorescence immunoassay for the quantitative determination of paclitaxel
      (Pac) under equilibrium conditions was developed. Anti-Pac IgG2a antibody was
      immobilized through its Fc region to protein A covalently bound to the inside
      surface of a silanized glass capillary column and the antigen-binding sites of
      anti-Pac saturated with rhodamine-labeled Pac (Rh-Pac). Analyte Pac was
      circulated through the column in a closed loop and the steady-state fluorescence
      of the Rh-Pac displaced from the immobilized antibody was recorded after 6 min.
      The Rh-Pac fluorescence emission intensity was directly related to the
      concentration of the Pac analyte over a broad dynamic range of up to 400 ng/ml
      with a linear range up to 200 ng/ml and lower detection limit of 5.85 ng/ml.
      While there was no interference from the baccatin III and 10-deacetylbaccatin
      III, cephalomannine was found to interfere in Pac determination. When applied for
      measurement of Pac in human plasma, the concentration of Pac determined by the
      fluorescence assay was found to be in excellent agreement with the Pac added,
      confirming the potential of the fluorescence immunoassay for clinical
      application.

PMID- 10929806
TI  - Design of fluorogenic substrates for continuous assay of sialyltransferase by
      resonance energy transfer.
AB  - Glycosyltransferases are important synthetic enzymes for the construction of
      naturally occurring glycoconjugates as well as for the design of
      neoglycoconjugates. The assay methods currently available for these enzymes
      require tedious and time-consuming procedures for separation of products and do
      not permit continual assay of enzyme activities. As a set of convenient
      fluorogenic substrates for continuous monitoring of sialyltransferase activities,
      we designed and synthesized a novel CMP-Neu5Ac derivative with a naphthylmethyl
      group at the C-9 position and N-acetyllactosamine derivative containing a dansyl
      group at the terminal position of aglycon. In such substrates, the emission peak
      of the naphthylmethyl group (lambdaem = 340 nm) of the glycosyl donor is
      successfully overlapped with the excitation peak due to the dansyl group
      (lambdaex = 335 nm) of the glycosyl acceptor. A coupling reaction of these two
      substrates catalyzed by rat liver 2,6-sialyltransferase caused an increase of
      dansyl fluorescence (lambdaem = 525 nm) and a decrease of naphthylmethyl
      fluorescence on the basis of resonance energy transfer between two fluorescence
      probes. The substrates presented here permit continuous fluorescent monitoring of
      enzymatic sugar combining reactions. Actually, using this time course of
      enzymatic reactions, kinetic constants of rat liver 2,6-sialyltransferase against
      glycosyl donor substrates were estimated to be Km = 4.85 microM and Vmax. = 0.119
      micromol/min, respectively. This strategy allows precise and efficient analyses
      of enzyme kinetics not possible with the conventional assay methods for the
      glycosyltransferases that usually require separation of products from the
      reaction mixture.

PMID- 10929807
TI  - Fluorescence-based assay for the interaction of small molecules with the human
      renal organic anion transporter 1.
AB  - Secretion of small molecules from the systemic blood circulation into urine is
      one of the physiologically essential functions of the kidney. The human organic
      anion transporter (hOAT1) is a key component in the renal tubular secretion of
      negatively charged molecules including a variety of important therapeutics. In
      some cases, compounds interacting with hOAT1 may induce pharmacokinetic drug-drug
      interactions or cause nephrotoxicity. We developed a fluorescence-based, 96-well
      format assay using CHO cells stably expressing hOAT1, which allows for the
      evaluation of interactions between small molecules and hOAT1. The assay is based
      on the inhibition of the transport of 6-carboxyfluorescein, a high-affinity hOAT1
      substrate (Km = 3.9 microM), which was identified as one of several fluorescent
      organic anions. The relative inhibition potency of various known hOAT1 substrates
      determined using the 6-carboxyfluorescein-based inhibition assay correlated well
      with their Km values, indicating that the fluorescent assay exhibits a proper
      specificity. This in vitro assay can be employed to evaluate the mechanism of
      renal clearance of organic anions, to assess potential drug-drug interactions
      and/or nephrotoxic effects of various therapeutics, and to screen for novel hOAT1
      inhibitors that could serve as efficient nephroprotectants.

PMID- 10929808
TI  - Molecular beacons for DNA biosensors with micrometer to submicrometer dimensions.
AB  - Ultrasensitive molecular beacon (MB) DNA biosensors, with micrometer to
      submicrometer sizes, have been developed for DNA/RNA analysis. The fluorescence
      based biosensors have been applied in DNA/ RNA detection without the need for a
      dye-labeled target molecule or an intercalation reagent in the testing solution.
      Molecular beacons are hairpin-shaped oligonucleotides that report the presence of
      specific nucleic acids. We have designed a surface-immobilizable biotinylated
      ssDNA molecular beacon for DNA hybridization at a liquid-solid interface. The MBs
      have been immobilized onto ultrasmall optical fiber probes through avidin-biotin
      binding. The MB DNA biosensor has been used directly to detect, in real time, its
      target DNA molecules without the need for a competitive assay. The biosensor is
      stable and reproducible. The MB DNA biosensor has selectivity with single base
      pair mismatch identification capability. The concentration detection limits and
      mass detection limits are 0.3 nM and 15 amol for a 105-microm biosensor, and 10
      nM and 0.27 amol for a submicrometer biosensor, respectively. We have also
      prepared molecular beacon DNA biosensor arrays for simultaneous analysis of
      multiple DNA sequences in the same solution. The newly developed DNA biosensors
      have been used for the precise quantification of a specific rat gamma-actin mRNA
      sequence amplified by the polymerase chain reaction.

PMID- 10929809
TI  - Purification of integral outer-membrane protein OmpC, a surface antigen from
      Salmonella typhi for structure-function studies: a method applicable to
      enterobacterial major outer-membrane protein.
AB  - Extraction of the outer-membrane porin, OmpC, from Salmonella typhi Ty21a was
      done by using a modified salt-extraction procedure. It was possible to extract
      only the major outer-membrane protein (OMP) from the crude membrane using this
      method. Aberrant lipopolysaccharide (LPS) production in the galE mutant Ty21a has
      resulted in more isoforms of OmpC and subsequently led to anomalous mobility in
      SDS-PAGE. The purity of the preparation was confirmed by denaturing urea SDS-PAGE
      and N-terminal sequencing. The major OMP extracts had LPS of both bound and free
      forms. The free form of LPS could be removed by gel filtration and the bound
      form, largely, was removed using ion-exchange chromatography and by passing
      through ultrafiltration devices. This method has been used to extract the native
      trimer of OmpC, the major OMP, in a large scale, for structure-function studies.
      S. typhi Ty21a OmpC preparation yielded reproducible diffraction-quality
      crystals. Extracts of porin from wild-type Escherichia coli HB101, grown under
      high osmolarity conditions, showed a single species of OMP on SDS-PAGE. This
      suggests the possible application of the method to other gram-negative bacterial
      porins.

PMID- 10929810
TI  - Quantitative method for biomarkers of collagen degradation using liquid
      chromatography tandem mass spectrometry.
AB  - Preclinical efficacy testing commonly involves studies that require considerable
      resources and time. One valuable tool in this endeavor is the characterization of
      relevant biomarkers. A method has been developed for the simultaneous
      determination of collagen biomarker candidates as an instrument in screening
      compounds for efficacy. Two potential candidates, the 3-hydroxypyridinium
      crosslinks pyridinoline and deoxypyridinoline, were selected for analysis in
      collagen degradation models. Tissue or urine samples were collected, prepared,
      and quantitated for the biomarkers using spiked calibration curves and liquid
      chromatography tandem mass spectrometry. The development of a quick and simple
      assay method would allow us to increase the chances for success in efficacy
      screening by eliminating compounds with poor biomarker profiles. The method
      proposed here appears to be more selective, convenient, precise (generally <10%
      RSD), accurate (generally <10% RE), and sensitive relative to previously
      established methodology.

PMID- 10929811
TI  - Determination of catechins in human urine subsequent to tea ingestion by high
      performance liquid chromatography with electrochemical detection.
AB  - The title determination was conducted by HPLC with electrochemical detection
      using an ODS column and a mobile phase of acetonitrile: 0.1 M phosphate buffer
      (pH 2.5) (15:85, v/v). The eight catechins, gallocatechin (GC), epigallocatechin
      (EGC), catechin (C), epicatechin (EC), epigallocatechin gallate (EGCg),
      gallocatechin gallate (GCg), epicatechin gallate (ECg), and catechin gallate
      (Cg), were detected at 0.6 V vs Ag/AgCl. Good linear relationships between
      current and amount were noted for 0.5-250 pmol of each catechin, with a
      correlation coefficient of 0.999 in each case. The detection limit for any one
      was 0.5 pmol (signal to noise ratio, S/N = 3). After the ingestion of 340 ml
      canned green tea, GC, EGC, C, and EC, mostly in conjugated form, were determined
      in urine samples. Conjugated catechins were hydrolyzed by enzymes using sulfatase
      and beta-glucuronidase. The time courses of the above four catechins showed a
      maxima at 1-3 h after tea ingestion. (+), (-)-EC and (+), (-)-C were present in
      canned tea.

PMID- 10929812
TI  - A protein biosensor for lactate.
AB  - Blood lactate is a clinically valuable diagnostic indicator. In this preliminary
      report we describe a protein biosensor for L-lactate based on beef heart lactate
      dehydrogenase (LDH). LDH was noncovalently labeled with 8-anilino-1-naphthalene
      sulfonic acid (ANS). The ANS-labeled LDH displayed an approximately 40% decrease
      in emission intensity upon binding lactate. This decrease can be used to measure
      the lactate concentration. The ANS-labeled LDH was further utilized in a new
      sensing format, polarization sensing, which is suitable for miniaturization to a
      point-of-care lactate monitor. However, temporal instability of beef heart LDH
      indicates the need for further protein engineering prior to development of a more
      robust lactate-sensing protein.

PMID- 10929813
TI  - Optimization of cDNA representational difference analysis for the identification
      of differentially expressed mRNAs.
AB  - Representational difference analysis (RDA) is a powerful and sensitive tool for
      identification of differentially expressed genes (M. Hubank and D. G. Schatz,
      1999, Methods Enzymol. 303, 325-349; 1994, Nucleic Acids Res. 22, 5640-5648) that
      will identify both up- and downregulated genes differentially expressed between
      two cDNA populations. This manuscript provides a thorough description of an
      optimized RDA method. This procedure while still based on the traditional RDA
      originally developed by Lisitsyn and co-workers(N. A. Lisitsyn, 1995, Trends
      Genet. 11, 303-307; N. A. Lisitsyn, F. S. Leach, B. Vogelstein, and M. H. Wigler,
      1994, Cold Spring Harbor Symp. Quant. BioL 59, 585-587; N. Lisitsyn, N. Lisitsyn,
      and M. Wigler, 1993, 259, 946-951) and modified by Hubank and Schatz for RNA
      (1994, Nucleic Acids Res. 22, 5640-5648) is improved and requires less starting
      material than many existing methods. Several key modifications are included (1).
      Size-exclusion gel-filtration microspin columns are used throughout the procedure
      to remove the primers and low molecular weight cDNAs. This results in reducing
      the number of ethanol precipitations required and in improving the yield of
      desirable amplification products (2). Elimination of the mung bean nuclease
      treatment in favor of a simple dilution of PCR serves as a means of markedly
      reducing the single-stranded cDNAs that can interfere with the amplification of
      differentially expressed products (3). The use of up to six unique noninteracting
      primers ensures that no anomalous amplification occurs due to carryover of
      primers or incomplete digestion from the ends of the cDNAs (4). A set of cDNA
      standards was developed and various concentrations were used to better
      characterize the ability of representational difference analysis to identify rare
      messages in a complex cDNA population (5). Integral to this manuscript, a
      detailed laboratory protocol is available from the authors (craig.byus@ucr.edu)
      and provides a step-by-step description of the modified procedure.

PMID- 10929814
TI  - Optimization of detergents for the assay of cathepsins B, L, S, and K.
AB  - The differential effects of representative, commonly available ionic (SDS),
      nonionic (Brij 35, Tween 20, and Triton X-100), and zwitterionic (Chaps)
      detergents on the catalytic activity and properties of human cathepsins B, L, S,
      and K were examined. The presence of detergents in the assay buffer affected the
      activity of cathepsins to variable extents; Chaps enhanced the activity of all
      the enzymes while SDS was most detrimental. Tween 20 lowered cathepsin S
      activity, while it slightly enhanced that of all other cathepsins studied. The
      presence of detergents in the activation buffer was clearly beneficial to both
      cathepsins L and K, possibly by favoring the release of the enzyme from the walls
      of the incubation vessel. Overall, the results indicate that Chaps is the optimal
      detergent for use with this family of enzymes.

PMID- 10929815
TI  - Characterization of probe binding and comparison of its influence on fluorescence
      lifetime of two pH-sensitive benzo[c]xanthene dyes using intensity-modulated
      multiple-wavelength scanning technique.
AB  - Quantitative pH imaging using the carboxy seminaphthofluorescein dyes SNAFL-1 and
      SNAFL-2 can be performed by measurement of intensity ratios or fluorescence
      lifetimes. However, there is a controversy as to whether the latter method has
      the practical advantage of a straightforward pH calibration in buffers compared
      to a cumbersome and time-consuming procedure in cells. In this study we have
      undertaken a systematic study of the potential factors influencing the
      fluorescence lifetime of the probes at different pH using confocal microscopy. In
      vitro results demonstrate that factors such as lipid and protein concentrations
      have a substantial influence on pH measurements based on fluorescence lifetime.
      The pH could be overestimated by more than 2 pH units. Studies in permeabilized
      COS-7 cells demonstrate the same trends as observed in the in vitro studies.

PMID- 10929816
TI  - Increased transformation efficiency of Aspergillus nidulans protoplasts in the
      presence of dithiothreitol.

PMID- 10929817
TI  - Improved in vivo dimethyl sulfate footprinting using AlkA protein: DNA-protein
      interactions at the mouse H19 gene promoter in primary embryo fibroblasts.

PMID- 10929818
TI  - Confounding factors in lanthanide ion probe spectrofluorometric assay of
      aminoglycoside antibiotics.

PMID- 10929819
TI  - Determination of mucin in salivary glands using sialic acids as the marker by
      high-performance liquid chromatography with fluorometric detection.

PMID- 10929820
TI  - From human-machine interaction to human-machine cooperation.
AB  - Since the 1960s, the rapid growth of information systems has led to the wide
      development of research on human-computer interaction (HCI) that aims at the
      designing of human-computer interfaces presenting ergonomic properties, such as
      friendliness, usability, transparency, etc. Various work situations have been
      covered--clerical work, computer programming, design, etc. However, they were
      mainly static in the sense that the user fully controls the computer. More
      recently, public and private organizations have engaged themselves in the
      enterprise of managing more and more complex and coupled systems by the means of
      automation. Modern machines not only process information, but also act on dynamic
      situations as humans have done in the past, managing stock exchange, industrial
      plants, aircraft, etc. These dynamic situations are not fully controlled and are
      affected by uncertain factors. Hence, degrees of freedom must be maintained to
      allow the humans and the machine to adapt to unforeseen contingencies. A human
      machine cooperation (HMC) approach is necessary to address the new stakes
      introduced by this trend. This paper describes the possible improvement of HCI by
      HMC, the need for a new conception of function allocation between humans and
      machines, and the main problems encountered within the new forms of human-machine
      relationship. It proposes a conceptual framework to study HMC from a cognitive
      point of view in highly dynamic situations like aircraft piloting or air-traffic
      control, and concludes on the design of 'cooperative' machines.

PMID- 10929821
TI  - The information and communication society: how people will live and work in the
      new millennium.
AB  - This paper analyses information and communication technology (ICT) and its
      relation to work organizations, human communication, stress, allocation issues,
      knowledge transfer and global villages. An interdisciplinary research programme
      on 'Computer technology and work life' was initiated and led by the author at
      Stockholm University in 1974, followed by many programmes in Sweden in the field.
      A theoretical framework was developed including two theoretical models, one more
      general, the other where the concepts and their interrelationships were
      specified. The models were tested empirically in three large work organizations
      in Sweden, representing three main historical periods of computer technology. It
      was also used as a model in discussing what might be desirable goals in the
      information society. The present fourth period, the 'Network period', is
      characterized by a convergence of three main technologies: computer,
      telecommunication and media. ICT is used in almost every activity and is embedded
      in many things. The author proposes a superimposed theoretical model reflecting
      'ICT and the psychosocial life environment', a revised model of her initial
      models. Finally, future research is discussed with reference to theoretical
      models revised, and conclusions address major psychosocial processes,
      psychosocial life environments and a call for synthesis.

PMID- 10929822
TI  - Culture, politics and ergonomics.
AB  - The beginning of a new century is an appropriate moment to consider the role of
      ergonomics in relation to the problems facing society. To help solve these
      serious global problems, ergonomics needs to be open to new disciplines,
      particularly those in the social sciences. Also, it may be difficult to
      generalize research on human-centred sociotechnical design without taking into
      account national characteristics, economics and political constraints. Currently
      there is more interest than ever in what ergonomics has to offer, but to deliver
      its promise requires a much broader approach than is usual. By adopting such new
      approaches one may help solve both the problems of the overdeveloped
      postindustrial societies and those of the societies of the Third World, where a
      new approach to work and economics may provide an improved chance for development
      given the recent changes in global economic policy.

PMID- 10929823
TI  - Human factors in a dynamic information society: where are we heading?
AB  - Society is becoming increasingly dynamic and integrated owing to the extensive
      use of information technology. This has several implications that pose new
      challenges to the human factors profession. In an integrated society, changes and
      disturbances propagate rapidly and widely and the increasing scale of operations
      requires also that rare events and circumstances are considered during systems
      design. In this situation, human factors contributions should be increasingly
      proactive, not only responding to observed problems, but also, they should be
      based on models of adaptive human behaviour in complex, dynamic systems. The
      paper suggests some methodological issues to consider for human factors analyses
      by designers, evaluators and teachers.

PMID- 10929824
TI  - Occupational low back disorder causation and control.
AB  - Low back disorders (LBDs) continue to be the most common musculoskeletal problem
      in the workplace. It affects many workers, is associated with high costs to
      industry and the individual, and can negatively influence the quality of life for
      the workers. Currently there is significant controversy about the work
      relatedness of LBD and the ability of ergonomics interventions to control the
      problem. This paper systematically examines the body of knowledge associated with
      LBDs and considers how information from different disciplines of study
      collectively might be used to assess the causality and control of LBD due to
      physical factors associated with work.

PMID- 10929825
TI  - Role of ergonomics in the transfer of technology to industrially developing
      countries.
AB  - Technological development has contributed to economic growth and social progress
      as well as a reduction of many sources of occupational accidents, injuries and
      stresses. However, advanced technology has also brought new sources of work
      stress and injuries. Industrially developing countries (IDC) have tended to try
      to achieve economic growth and development by importing technology designed for
      IDC. However, because of several complex technical, cultural and socio-economic
      factors, this policy has not been always successful. Inappropriate technology
      transfer has led to many work environment and productivity problems.
      Consideration of ergonomics in the choice and utilization of the transferred
      technology can help to create a good fit between technology, technology users and
      the operating environment. Application of ergonomics is, however, not widely
      spread in most IDC. Ergonomics input will create the appropriate working
      environment in which people are safe and motivated to participate and can better
      utilize company resources for increasing system productivity, reliability and
      availability.

PMID- 10929826
TI  - Parts of life: configuring equipment to individual lifestyle.
AB  - Usability is the standard criterion for interactive products in human factors
      engineering and can be measured in terms of effectiveness, efficiency,
      learnability and satisfaction. Yet many products that satisfy these criteria are
      not used and in the past have faded away from the product scene. Other products
      that do not satisfy these criteria at all may be used quite extensively and have
      sometimes found wide, if not global, acceptance. There must be other factors than
      usability that predispose people to use particular products. On the basis of an
      evaluation study on a videophone system, a number of issues have been analysed
      that throw more light on why people like to use certain products. One important
      aspect is to what extent interactive products fit into the daily lifestyle and
      the personal environment of the user. The more complex products get, and the more
      functionalities they acquire, matching to individual lifestyle becomes more
      important, and, consequently, the more configurable these products have to be.
      This is an underestimated aspect of the design of interactive products that
      apparently will need increasing input from human and cognitive engineering.

PMID- 10929827
TI  - Ergonomics in the past and the future: from a German perspective to an
      international one.
AB  - Looking at the past there are more or less fragmented approaches in ergonomics as
      well as in management. Especially in Germany, the 'Lean Management wave' weakened
      ergonomics in industry. On the other hand, there is a growing demand for holistic
      concepts--and ergonomics can by definition be understood as holistic. Many of the
      newer approaches in management include ODAM or macro-ergonomics elements. In
      building up a stronger relationship between macro- and micro-ergonomics, the
      whole discipline could be promoted. This also requires the fulfillment of some
      preconditions like systematically gathering and presenting 'best practices',
      which show that ergonomics pays off.

PMID- 10929828
TI  - Designing automation for human use: empirical studies and quantitative models.
AB  - An emerging knowledge base of human performance research can provide guidelines
      for designing automation that can be used effectively by human operators of
      complex systems. Which functions should be automated and to what extent in a
      given system? A model for types and levels of automation that provides a
      framework and an objective basis for making such choices is described. The human
      performance consequences of particular types and levels of automation constitute
      primary evaluative criteria for automation design when using the model. Four
      human performance areas are considered--mental workload, situation awareness,
      complacency and skill degradation. Secondary evaluative criteria include such
      factors as automation reliability, the risks of decision/action consequences and
      the ease of systems integration. In addition to this qualitative approach,
      quantitative models can inform design. Several computational and formal models of
      human interaction with automation that have been proposed by various researchers
      are reviewed. An important future research need is the integration of qualitative
      and quantitative approaches. Application of these models provides an objective
      basis for designing automation for effective human use.

PMID- 10929829
TI  - Human factors and aviation safety: what the industry has, what the industry
      needs.
AB  - The use of statistical analyses to assert safety levels has persuasively been
      established within the aviation industry. Likewise, variations in regional
      statistics have led to generalizations about safety levels in different contexts.
      Caution is proposed when qualitatively linking statistics and aviation's
      resilience to hazards. Further caution is proposed when extending generalizations
      across contexts. Statistical analyses--the favoured diagnostic tool of aviation-
      show sequences of cause/effect relationships reflecting agreed categorizations
      prevalent in safety breakdowns. They do not, however, reveal the processes
      underlying such relationships. It is contended that the answers to the safety
      questions in contemporary aviation will not be found through the numbers, but
      through the understanding of the processes underpinning the numbers. These
      processes and their supporting beliefs are influenced by contextual constraints
      and cultural factors, which in turn influence individual and organizational
      performance. It is further contended that the contribution of human factors is
      fundamental in achieving this understanding. This paper, therefore (1) argues in
      favour of a macro view of aviation safety, (2) suggests the need to revise a long
      standing safety paradigm that appears to have ceased to be effective, and (3)
      discusses the basic premises upon which a revised safety paradigm should build.

PMID- 10929830
TI  - Activity theory as a framework for analyzing and redesigning work.
AB  - Cultural-historical activity theory is a new framework aimed at transcending the
      dichotomies of micro- and macro-, mental and material, observation and
      intervention in analysis and redesign of work. The approach distinguishes between
      short-lived goal-directed actions and durable, object-oriented activity systems.
      A historically evolving collective activity system, seen in its network relations
      to other activity systems, is taken as the prime unit of analysis against which
      scripted strings of goal-directed actions and automatic operations are
      interpreted. Activity systems are driven by communal motives that are often
      difficult to articulate for individual participants. Activity systems are in
      constant movement and internally contradictory. Their systemic contradictions,
      manifested in disturbances and mundane innovations, offer possibilities for
      expansive developmental transformations. Such transformations proceed through
      stepwise cycles of expansive learning which begin with actions of questioning the
      existing standard practice, then proceed to actions of analyzing its
      contradictions and modelling a vision for its zone of proximal development, then
      to actions of examining and implementing the new model in practice. New forms of
      work organization increasingly require negotiated 'knotworking' across
      boundaries. Correspondingly, expansive learning increasingly involves horizontal
      widening of collective expertise by means of debating, negotiating and
      hybridizing different perspectives and conceptualizations. Findings from a
      longitudinal intervention study of children's medical care illuminate the
      theoretical arguments.

PMID- 10929831
TI  - New paradigm, new market and new theatre in ergonomics.
AB  - Change is the only constant in today's technology-driven world. As industry moves
      towards an unprecedented revolution, the momentum and impact of the change are
      both rapid and profound. This will affect our profession drastically. We will
      need to redefine our goals and strategies to cope with these new challenges. In
      this paper, a new paradigm of thinking, a new market for our discipline and a new
      theatre of ergonomics in the future are proposed and explained.

PMID- 10929832
TI  - Co-operation at work: a process-oriented perspective on joint activity in inter
      organizational relations.
AB  - In this paper the authors present a conceptual framework for analysing co
      operation between organizations as a situated process, highlighting co-operation,
      co-ordination and co-construction as different modes of joint activity. Within
      this framework, the analysis of unexpected events becomes a crucial issue. The
      analytic power of reconstructing the (psycho-) logics of unexpected events in
      inter-organizational relations will be demonstrated in the presentation of
      selected outcomes of a research project on the dynamics of producer-supplier
      relationships in the German automobile industry. Also in this empirical part, the
      significance of trust and confidence in inter-organizational relations will be
      reflected.

PMID- 10929833
TI  - Usability testing in 2000 and beyond.
AB  - Usability testing is a widely used technique to evaluate user performance and
      acceptance of products and systems. It was introduced in the late 1980s and rose
      to popularity in the past decade. This paper provides a view of the current
      status of usability testing as a method and describes how it will be used in the
      21st century. Although usability testing may not be the most efficient technique
      for discovery of usability problems, it is a reliable way to estimate
      quantitatively users' performance and subjective satisfaction with products. Four
      major trends in usability testing include: common reporting formats and methods
      for industry; Internet application and website testing; testing of mobile,
      handheld devices; and testing in more naturalistic environments such as simulated
      homes and classrooms. In the 21st century, 'quick and clean' usability testing
      methods are needed to provide valid and reliable data on how well people use
      products and systems, and how they like using them.

PMID- 10929834
TI  - Ergonomics strategies and actions for achieving productive use of an ageing work
      force.
AB  - In this report, a basic ERGOMA (Ergonomics in Industrial Management) strategy is
      proposed as a policy for corporate production and employment in countries where
      ageing populations and reduced birth rates are imminent, and a strategy related
      to this is proposed. Specifically, as a strategy at the company level, the
      results of survey studies aimed at the development of methods for determining job
      capacity, to enable effective use of the labour of ageing workers, were
      summarized. A number of the insights gained here are steps in the development of
      a foundational methodology for practical use, and in actual practice a number of
      these insights must be subjected to measurements. However, the theory and newly
      developed methodology described here are thought to represent significant changes
      from the approaches to job capacity diagnosis and assessment published in the
      past and from the stance towards utilization of an ageing work-force. The author
      is confident that this represents new progress in one of the ergonomics approach
      to dealing with the working environment of ageing workers and an ageing work
      force in general.

PMID- 10929835
TI  - Where are we in understanding the effects of where we are?
AB  - This paper briefly reviews research studies of interest to environmental
      ergonomists. It includes some recent work on the health effects of office
      lighting, especially the effects of daylighting, fluorescent lighting and full
      spectrum lighting. It also covers studies of indoor air quality in offices,
      especially investigations of localized air filtration and the sick building
      syndrome. It argues the value of a systematic, ergonomics approach to designing
      the built environment.

PMID- 10929836
TI  - Ergonomics user interface standards: are they more trouble than they are worth?
AB  - The purpose of this paper is to review the history, progress and results of one
      area of international standardization--the ergonomics of human-system
      interaction. It is a personal perspective based on my experiences as Chairman of
      ISO/TC159/SC4 over the past 17 years. The paper starts with some historical
      background and summarizes the main work of the Committee. It then identifies five
      areas where the results of the standardization work could have been more
      successful and discusses what went wrong. These problems include the long time
      scale for development, how the standards were misunderstood, how political the
      process can be, how we may have tried to be too clever and how the abundance of
      help at times may have been a problem. The paper concludes with an explanation of
      why the activity and the results were not all bad. The five positive areas
      include the benefits that can come from the slow pace of the work, the benefits
      of structure and formality, why standards do not have to be restrictive, how the
      standards themselves are only part of the outcome and how being a truly
      international experience makes it all worthwhile.

PMID- 10929837
TI  - For the billionth time!

PMID- 10929838
TI  - Adolescent pregnancy rates in three European countries: lessons to be learned?
AB  - Adolescent pregnancy and abortion rates in the Netherlands, France, and Germany
      are lower than rates in the United States and the mean age of sexual debut is
      later. Contributing factors include philosophical differences about the rights
      and responsibilities of adolescents, access to contraceptives, sexuality
      education, and mass media campaigns. The data used in this article were gathered
      from meetings with health care providers in the three European countries studied
      and from published reports. While it is not possible to impose practices from one
      society upon another, nurses in North America may want to consider implementing
      some of these ideas in their practices.

PMID- 10929839
TI  - Pregnancy after a TRAM flap procedure: principles of nursing care.
AB  - Breast cancer is the most common malignancy in women in the United States and
      affects more than 200,000 women annually. The incidence increases exponentially
      with age from the 3rd to the 5th decade of life. Many women are now choosing to
      have a more natural breast reconstruction concomitantly with their mastectomy. A
      TRAM (transverse rectus abdominis myocutaneous) flap is a procedure to
      reconstruct the breast mound using autologous tissue. Women of childbearing age
      who have undergone a TRAM flap may safely consider pregnancy after such a
      procedure. The principles of nursing care for pregnant women who have undergone a
      TRAM flap surgery are presented in this article. A case report of pregnancy after
      a TRAM flap is included.

PMID- 10929840
TI  - Linking substance-abusing pregnant women to drug treatment services: a pilot
      program.
AB  - OBJECTIVE: To conduct a pilot study to assist pregnant substance abusers to enter
      drug treatment. DESIGN: A nonexperimental design provided eligible women with
      outreach/home visits from a team led by a public health nurse. SETTING: All
      services for the women were provided in homes in the northeastern United States.
      PARTICIPANTS: Ten pregnant substance-abusing women who were not in drug treatment
      upon entry into prenatal care enrolled in the project. INTERVENTIONS: Home visits
      by a public health nurse were provided to the women to jointly develop a plan of
      care targeted to each woman's needs. A substance abuse counselor was available as
      a consultant and for home visits. An interdisciplinary team met monthly to
      coordinate services, discuss therapeutic approaches and treatment strategies, and
      address needed changes in the health services system. MAIN OUTCOME MEASURES:
      Rates of entry into substance abuse treatment, retention of custody of the index
      child, and scores on the Addiction Severity Index (ASI). RESULTS: Although the
      expected rate of entry into treatment was 10%, 90% of the women (n = 9) entered
      treatment. All had full-term newborns. Eighty percent (n = 8) retained custody of
      the index child. Upon the participants' enrollment, ASI scores indicated a
      moderate to extreme problem with alcohol and drug use for all women, and moderate
      to extreme psychiatric problems for 89% of the women. Subsequent ASI scores
      demonstrated marked improvement in all three subscales. CONCLUSION: This project
      provides strategies that nurses can use to assist substance-abusing pregnant
      women to enter drug treatment.

PMID- 10929841
TI  - Is it difficult to concentrate during the 3rd trimester and postpartum?
AB  - OBJECTIVE: The purpose of this study was to examine changes in women's directed
      attention, the ability to focus or concentrate, during the last trimester of
      pregnancy and during 1st week postpartum. DESIGN: Pregnant women were tested at
      enrollment (during the 3rd trimester), at 37 weeks gestation, and during the 1st
      postpartum week for this descriptive, repeated measures study. SETTING: Women
      were recruited from childbirth education classes in southwestern Michigan.
      PARTICIPANTS: Fifty-seven women in their 3rd trimester of pregnancy. MAIN OUTCOME
      MEASURES: Directed attention was measured objectively by the Digits Span Forward
      and Backward, Trailmaking A and B, and Category Matching tests. Subjective
      measures were the Attentional Function Index and Mental Effort in Tasks tests.
      RESULTS: Participant means on the objective measures were within the normal range
      at all three time points. Some individuals, however, showed limitations in the
      capacity to direct their attention. Ability to use directed attention was lowest
      at enrollment and improved during the study, with statistically significant
      changes from Times 1 to 2 on several measures. Subjectively, the participants
      felt that they had moderately low competence on tasks that required directed
      attention throughout the study. CONCLUSIONS: Women had the greatest difficulty
      focusing during the 3rd trimester. Some individuals had problems with tasks
      requiring directed attention at all three time points. Many participants
      perceived that their ability to pay attention was lower than normal. Some women
      may benefit from nursing interventions to reduce attentional demands during the
      3rd trimester and early postpartum period.

PMID- 10929842
TI  - Factors related to sucking ability in healthy newborns.
AB  - OBJECTIVE: To identify maternal, infant, and environmental factors related to
      newborn sucking ability. DESIGN: Prospective, descriptive, exploratory study
      using a convenience sample. SETTING: Normal newborn nursery in an urban tertiary
      care medical center. PARTICIPANTS: Two hundred three healthy newborns admitted to
      the normal newborn nursery after delivery. The newborns were between 30 minutes
      and 11 hours of age, and between 34 and 42 weeks gestation. MAIN OUTCOME
      MEASURES: This study examined 15 variables related to newborn sucking ability:
      infant state, age, gestational age, Apgar scores, birth weight, labor
      medications, type of delivery, elapsed time since last feeding, infant sex,
      perinatal complications, infant vital signs, birth resuscitation, clothing, room
      temperature, and length of labor. Sucking ability was measured by the Neonatal
      Oral Motor Assessment Scale (NOMAS). RESULTS: The variables of gestational age,
      weight, and state were positively correlated with sucking ability (NOMAS scores).
      Newborn's age postdelivery and minutes to the quiet alert state were inversely
      correlated with sucking ability. CONCLUSIONS: Newborn weight and gestational age
      are related to sucking ability. Younger newborns had better sucking ability than
      did older newborns.

PMID- 10929843
TI  - Menopause: Irish women's voices.
AB  - OBJECTIVE: To gain an understanding of the cultural meanings of menopause for
      Irish women. DESIGN: Phenomenological, using Colaizzi's methodology to focus on
      the menopausal stories of Irish women. PARTICIPANTS AND SETTING: Six Irish women
      who were postmenopausal by 1-6 years were interviewed about their experiences.
      The participants were all mothers of five or more surviving children, chosen to
      exclude women who may have wished for more children. These women lived in small
      villages in rural southern Ireland. The taped interviews were conducted in the
      participants' homes. RESULTS: The sociocultural context of menopause in Ireland
      is described, including common perceptions of fertility and social timing of
      childbirth, and the meaning and significance of loss of fertility at menopause.
      The predominant themes found were a shared sense of relief at reaching menopause,
      a sense of acceptance of menopause as a natural event in a woman's life cycle,
      and a sense of satisfaction at having successfully raised their families to
      adulthood. There was also a bittersweet paradox of associated menopausal
      symptoms, particularly heavy bleeding. CONCLUSION: Rural Irish women in this
      study experience menopause as a normal process of aging and do not associate it
      with illness. Their experiences are strongly contextual and support the view that
      menopause is a complex phenomenon experienced within a sociocultural context.

PMID- 10929844
TI  - Cancer and pregnancy: a health care dilemma.
AB  - When cancer occurs during pregnancy, a conflict exists between the family's hopes
      and dreams for the future and the reality of the diagnosis of a potentially
      terminal illness. The nurse has a pivotal role in the assessment and management
      of the pregnant oncologic patient's physical and emotional health. The perinatal
      nurse must assure that the care experienced by the family balances the reality of
      a potentially life-threatening illness with the joy that accompanies the birth of
      a baby.

PMID- 10929845
TI  - Sexual implications of gynecologic cancer treatments.
AB  - Gynecologic cancers affected 81,000 women in 1999. The disease and its associated
      treatment commonly pose a threat not only to the life of such patients, but also
      to their sexuality and fertility. These women and their partners require
      knowledgeable, compassionate care. Effective, holistic nursing care for women
      experiencing gynecologic cancers requires an understanding of basic concepts of
      female sexuality, the diagnosis and treatment of gynecologic malignancies, the
      impact of the disease and its treatment on a woman's sexuality, and ways the
      nurse can incorporate sexuality issues into practice.

PMID- 10929846
TI  - Neonatal cancer: a clinical perspective.
AB  - The diagnosis of a neonatal malignancy, while rare, requires complex
      knowledgeable care from members of the health care team. The neonatal intensive
      care nurse plays an important role on that team. The types of malignancies found
      in neonates differ from those in older children, as do the neonate's responses to
      treatment. A review of the presentation, diagnosis, and management of the more
      common types of neonatal malignancies provides the context for consideration of
      the nurse's role in providing specialized care to neonates with cancer.

PMID- 10929847
TI  - Prophylactic mastectomy or screening in women suspected to have the BRCA1/2
      mutation: a prospective pilot study of women's treatment choices and medical and
      decision-analytic recommendations.
AB  - BACKGROUND: Women suspected to have the BRCA1/2 mutation may choose between two
      management options: breast cancer screening and prophylactic mastectomy (PM).
      OBJECTIVES: To compare women's treatment choices with medical and decision
      analytic recommendations and to explore variables related to the women's choices.
      METHODS: After provision of information, individual time-tradeoff values for the
      health outcome "living after PM" were assessed and incorporated into a decision
      analytic model, which compared the management options PM and screening with
      respect to their effects on quality-adjusted life expectancy. RESULTS: Of the 54
      women suspected to have the mutation, 51 completed the shared-decision-making
      procedure. Quality-adjusted life expectancy after PM management was longer for
      67% of proven carriers and for 58% of women awaiting the DNA-test result. Twelve
      proven carriers made definitive treatment choices: eight (67%) chose PM and four
      (33%) chose screening. All carriers' treatment choices agreed with the normative
      decision-analytic recommendations. Four (33%) disagreed with the medical
      recommendations. Of the 36 women awaiting DNA-test results, 32 made hypothetical
      treatment choices. The agreement between these hypothetical treatment choices and
      the decision-analytic recommendations was good (78%). Combining data from all 48
      women, being married (OR = 14.00, p = 0.006), having children (OR = 4.71, p =
      0.02), low desire to participate (OR = 0.14, p = 0.004), high decisional stress
      (OR = 5.22, p = 0.01), a lower estimate of the "probability of cure for screen
      detected breast cancer" (OR = 0.13, p = 0.004), and higher time-tradeoff values
      for PM (OR = 182, p < 0.0001) made a choice for PM more likely. CONCLUSIONS: The
      complete agreement between the decision-analytic recommendations and the
      carriers' choices suggests that women act in accordance with normative decision
      theory. The disagreement between the carriers' choices and the medical
      recommendations suggests that women's choices and physicians' recommendations
      were guided by different arguments. The strong association between time-tradeoff
      value and treatment choice suggests that the time-tradeoff is a valid method to
      assess preferences.

PMID- 10929848
TI  - Population-based time preferences for future health outcomes.
AB  - CONTEXT: Time preference (how preference for an outcome changes depending on when
      the outcome occurs) affects clinical decisions, but little is known about
      determinants of time preferences in clinical settings. OBJECTIVES: To determine
      whether information about mean population time preferences for specific health
      states can be easily assessed, whether mean time preferences are constant across
      different diseases, and whether under certain circumstances substantial fractions
      of the patient population make choices that are consistent with a negative time
      preference. DESIGN: Self-administered survey. SETTING: Family physician waiting
      rooms in four states. PATIENTS: A convenience sample of 169 adults. INTERVENTION:
      Subjects were presented five clinical vignettes. For each vignette the subject
      chose between interventions maximizing a present and a future health outcome. The
      options for individual vignettes varied among the patients so that a distribution
      of responses was obtained across the population of patients. MAIN OUTCOME
      MEASURE: Logistic regression was used to estimate the mean preference for each
      vignette, which was translated into an implicit discount rate for this group of
      patients. RESULTS: There were marked differences in time preferences for future
      health outcomes based on the five vignettes, ranging from a negative to a high
      positive (116%) discount rate. CONCLUSIONS: The study provides empirical evidence
      that time preferences for future health outcomes may vary substantially among
      disease conditions. This is likely because the vignettes evoked different
      rationales for time preferences. Time preference is a critical element in patient
      decision making and cost-effectiveness research, and more work is necessary to
      improve our understanding of patient preferences for future health outcomes.

PMID- 10929849
TI  - Modal preferences predict elderly patients' life-sustaining treatment choices as
      well as patients' chosen surrogates do.
AB  - The purpose of this study was to compare the accuracy of an actuarial method of
      predicting patients' preferences for life-sustaining treatment with the accuracy
      of surrogate decision makers. 401 outpatients 65 years old or older (mean = 73
      years) and their self-designated surrogate decision makers recorded preferences
      for four life-sustaining medical treatments in nine hypothetical illness
      scenarios. The surrogates did not predict the patients' preferences more
      accurately than did an actuarial model using modal preferences. Surrogates'
      accuracy was not influenced by the use of an advance directive (AD) or discussion
      of life-sustaining treatment choices. In clinical practice, an actuarial model
      could assist surrogate decision makers when a patient has no AD, an AD is
      unavailable, a patient's AD is vague or describes treatment choices for only
      extreme or unlikely disease states, no proxy decision maker has been designated,
      or a patient was never competent.

PMID- 10929850
TI  - Comparison of Finnish and U.S.-based visual analog scale valuations of the EQ-5D
      measure.
AB  - The EQ-5D is a multiattribute health status measure that can be used to derive
      preference-based index scores for health-related quality-of-life (HRQOL)
      assessment. Valuations for EQ-5D health states using different techniques have
      been obtained in a number of countries. It is not clear how valuations from
      different countries compare. Using an ordinary least-squares regression, visual
      analog scale valuations for EQ-5D health states obtained in postal surveys in
      Finland and the United States were compared. The regression model estimates
      indicated that Finnish and U.S. respondents did provide different preference
      valuations for different levels of health. However, the country-specific
      differences were not large and depended on the dimension and the level of problem
      on that dimension. Differences in health-state valuations are unlikely to have
      important implications when using the EQ-5D in international studies.

PMID- 10929851
TI  - The effectiveness of one-to-one risk communication interventions in health care:
      a systematic review.
AB  - OBJECTIVES: To assess whether risk-communication interventions are associated
      with changes in patient knowledge, attitudes, and behaviors, and to identify
      aspects of these interventions that modify these effects. DESIGN: Systematic
      review. DATA SOURCES: 96 studies from the period 1985-1996 retrieved by
      electronic searching of eight databases, hand searching of four journals,
      contacting key authors, and reference list searching. MAIN OUTCOME MEASURES: The
      effect size of the principal outcome was identified from each study. Outcomes
      measuring behavioral change were preferred; if these were not available,
      knowledge, anxiety, or risk perceptions were used, according to the focus of the
      study. Data were available to calculate the principal effect sizes for 82 of the
      studies. ANALYSIS: Meta-regression. RESULTS: The methodologic qualities of the
      studies varied. Nevertheless, risk-communication interventions generally had
      positive (beneficial) effects. Interventions addressing treatment choices were
      associated with larger effects than were those in other contexts, such as
      prevention or screening. Interventions using individual risk estimates were
      associated with larger effects than were those using more general risk
      information. Two design variables were identified as effect modifiers: randomized
      controlled trials were associated with smaller effects than other designs, and
      dichotomous outcomes were associated with larger effects than continuous
      outcomes. CONCLUSIONS: Risk communication interventions may be most productive if
      they include individual risk estimates in the discussion between professional and
      patient. Patient decisions about treatment appear more amenable to change by
      these interventions than attendance for screening or modification of risky
      behavior.

PMID- 10929852
TI  - A new scale for assessing perceptions of chance: a validation study.
AB  - BACKGROUND: Clinicians and researchers often wish to know how patients perceive
      the likelihoods of health risks. Little work has been done to develop and
      validate scales and formats to measure perceptions of event probabilities,
      particularly low probabilities (i.e., <1%). OBJECTIVE: To compare a new visual
      analog scale with three benchmarks in terms of validity and reliability. DESIGN:
      Survey with retest after approximately two weeks. Respondents estimated the
      probabilities of six events with the new scale, which featured a "magnifying
      glass" to represent probabilities between 0 and 1% on a logarithmic scale.
      Participants estimated the same probabilities on three benchmarks: two linear
      visual analog scales (one labeled with words, one with numbers) and a "1 in x"
      scale. SUBJECTS: 100 veterans and family members and 107 university faculty and
      students. MEASURES: For each scale, the authors assessed: 1) validity-the
      correlation between participants' direct rankings (i.e., numbering them from 1 to
      6) and scale-derived rankings of the relative probabilities of six events; 2)
      test-retest reliability-the correlation of responses from test to retest two
      weeks later; 3) usability (missing/ incorrect responses, participant evaluation).
      RESULTS: Both the magnifier and the two linear scales outperformed the "1 in x"
      scale on all criteria. The magnifier scale performed about as well as the two
      linear visual analog scales for validity (correlation between direct and scale
      derived rankings = 0.72), reliability (test-retest correlation = 0.55), and
      usability (2% missing or incorrect responses, 65% rated it easy to use). 62% felt
      the magnifier scale was a "very good or good" indicator of their feelings about
      chance. The magnifier scale facilitated expression of low-probability judgments.
      For example, the estimated chance of parenting sextuplets was orders of magnitude
      lower on the magnifier scale (median perceived chance 10(-5)) than on its linear
      counterpart (10(-2)). Participants' assessments of high-probability events (e.g.,
      chance of catching a cold in the next year) were not affected by the presence of
      the magnifier. CONCLUSIONS: The "1 in x" scale performs poorly and is very
      difficult for people to use. The magnifier scale and the linear number scale are
      similar in validity, reliability, and usability. However, only the magnifier
      scale makes it possible to elicit perceptions in the low-probability range (<1%).

PMID- 10929853
TI  - Beliefs about breast cancer risk and use of postmenopausal hormone replacement
      therapy.
AB  - BACKGROUND: Postmenopausal hormone replacement therapy (HRT) decreases the risks
      of coronary heart disease and osteoporosis, but increases the risk of breast
      cancer. Although only 20-30% of postmenopausal women in the United States take
      HRT, the relationship between breast cancer risk perception and use of HRT is not
      known. OBJECTIVE: To assess the impact of belief that HRT increases breast cancer
      risk and high perceived risk of breast cancer on the use of HRT. DESIGN: Cross
      sectional mailed survey. PARTICIPANTS: 189 randomly selected postmenopausal women
      from a general internal medicine practice in the Philadelphia area. MAIN RESULTS:
      Of the 268 women (67%) who returned surveys, 189 were postmenopausal; 70 (37%)
      were currently using HRT and 21 (11 %) had previously used HRT. Respondents' mean
      age was 59.6 years; 64% were Caucasian, and 33% had completed college. Fifty-nine
      women (33%) thought HRT increased the risk of breast cancer, 22 (12%) thought it
      did not, and 100 (55%) were unsure. Mean perceived lifetime risk of breast cancer
      was 31% (range 0%-100%). After multivariate adjustment, current use of HRT was
      inversely associated with age (OR 0.96 for each one-year increase, 95% CI
      0.940.98), and positively associated with Caucasian race (OR 2.73, 95% CI 1.40
      5.32). Use of HRT was not associated with belief that HRT increases the risk of
      breast cancer, breast cancer risk perception, or perceived severity of breast
      cancer. CONCLUSIONS: Belief that HRT increases the risk of breast cancer and high
      perceptions of breast cancer risk may not be important barriers to use of HRT.
      Efforts to improve decision making about HRT should focus on previously
      established barriers, such as perceptions of menopause and lack of physician
      discussion, rather than misconceptions about breast cancer risk.

PMID- 10929854
TI  - Representing both first- and second-order uncertainties by Monte Carlo simulation
      for groups of patients.
AB  - Actual implementation of probabilistic sensitivity analysis may lead to
      misleading or improper conclusions when it is applied to groups of patients
      rather than individual patients. The practice of combining first- and second
      order simulations when modeling the outcome for a group of more than one patient
      yields an erroneous marginal distribution whenever the parameter values are
      randomly sampled for each patient while the results are presented as simulated
      means for the group of patients. This practice results in underrepresenting the
      second-order uncertainty. It may also distort the shape (especially the symmetry
      or extent of the tails) in the simulated distribution. As a result, it may lead
      to premature or incorrect conclusions of superiority. It may also result in
      inappropriate estimates of the value of further research to inform parameter
      values.

PMID- 10929855
TI  - Comparing three-class diagnostic tests by three-way ROC analysis.
AB  - Three-way ROC surfaces are based on a generalization of dichotomous ROC analysis
      to three-class diagnostic tests. The discriminatory power of three-class
      diagnostic tests is measured by the volume under the ROC surface. This measure
      can be given a probabilistic interpretation similar to the equivalence of the c
      index to the area under the ROC curve. This article presents a method to
      calculate nonparametric estimates of the variance of the volume under the surface
      using Mann-Whitney U statistics. As a simple extension of this result, it is
      possible to calculate covariance estimates for the volume under the surface. This
      allows the statistical comparison of two tests used for diagnostic tasks with
      three possible outcomes. The formulas derived are validated on synthetic data and
      applied to a three-class data set of pigmented skin lesions. It is shown that a
      neural network algorithm trained on clinical data and lesion features performs
      better than one trained on only the lesion features.

PMID- 10929856
TI  - Willingness to pay for a quality-adjusted life year: in search of a standard.
AB  - Cost-benefit analysis (CBA) provides a clear decision rule: undertake an
      intervention if the monetary value of its benefits exceed its costs. However, due
      to a reluctance to characterize health benefits in monetary terms, users of cost
      utility and cost-effectiveness analyses must rely on arbitrary standards (e.g., <
      $50,000 per QALY) to deem a program "cost-effective." Moreover, there is no
      consensus regarding the appropriate dollar value per QALY gained upon which to
      base resource allocation decisions. To address this, the authors determined the
      value of a QALY as implied by the value-of-life literature and compared this
      value with arbitrary thresholds for cost-effectiveness that have come into common
      use. A literature search identified 42 estimates of the value of life that were
      appropriate for inclusion. These estimates were classified by method: human
      capital (HK), contingent valuation (CV), revealed preference/job risk (RP-JR) and
      revealed preference/non-occupational safety (RP-S), and by U.S. or non-U.S.
      origin. After converting these value-of-life estimates to 1997 U.S. dollars, the
      life expectancy of the study population, age-specific QALY weights, and a 3% real
      discount rate were used to calculate the implied value of a QALY. An ordinary
      least-squares regression of the value of a QALY on study type and national origin
      explained 28.4% of the variance across studies. Most of the explained variance
      was attributable to study type; national origin did not significantly affect the
      values. Median values by study type were $24,777 (HK estimates), $93,402 (RP-S
      estimates), $161,305 (CV estimates), and $428,286 (RP-JR estimates). With the
      exception of HK, these far exceed the "rules of thumb" that are frequently used
      to determine whether an intervention produces an acceptable increase in health
      benefits in exchange for incremental expenditures.

PMID- 10929857
TI  - A signal-detection experiment measuring the effect of computer-aided detection on
      radiologists' performance.
AB  - PURPOSE: To evaluate how the specificity and sensitivity of computer-aided
      detection (CADe) algorithm outputs affected radiologists' diagnostic
      performances, the authors studied the effects of 25 simulated CADe algorithms
      with various sensitivities and specificities (from 60% to 100%). METHODS: Six
      novice radiologists read 200 images that were produced by computer and randomly
      displayed on CRT, and their detection performances were evaluated with receiver
      operating characteristic analysis. RESULTS: There were significant differences in
      performance among CADe types (p < 0.001). DISCUSSION AND CONCLUSION: The overall
      accuracy of CADe outputs is the most significant factor affecting radiologists'
      performances in detection and interpretation of images. There is an approximately
      linear relationship between the sensitivity (specificity) of the CADe output and
      the reader's sensitivity (specificity), and the slope of reader sensitivity
      (specificity) as a linear function of CADe sensitivity (specificity) can be
      considered to be a positive number less than unity.

PMID- 10929858
TI  - How treatment advances affect prevention's cost-effectiveness: implications for
      the funding of medical research.

PMID- 10929859
TI  - Diagnostic strategy in uncertainty.

PMID- 10929860
TI  - Law and ethics.

PMID- 10929861
TI  - Judgmental psychology.

PMID- 10929863
TI  - A comparison of the clinical efficacy and safety of intranasal fluticasone
      propionate and antihistamines in the treatment of rhinitis.
AB  - Adequate management of allergic rhinitis is needed to avoid its considerable
      adverse social, clinical, and economic impact. Both topical intranasal steroids
      and oral or topical antihistamines are recognised as effective treatments for
      this condition. In comparative studies, however, intranasal steroids and, in
      particular, fluticasone propionate aqueous nasal spray (FPANS), have afforded
      consistently better symptomatic relief, and have a greater beneficial effect on
      quality of life. Furthermore, the addition of an antihistamine to FPANS therapy
      has generally produced little further benefit. Intranasal administration is
      associated with a low systemic absorption of fluticasone propionate and,
      following regular use of FPANS, placebo, or an oral antihistamine, no significant
      differences were seen between treatment groups in plasma or urinary cortisol.
      Overall, therefore, the data indicate that FPANS is superior to second-generation
      antihistamines in the management of allergic rhinitis.

PMID- 10929862
TI  - A comparison of the anti-inflammatory properties of intranasal corticosteroids
      and antihistamines in allergic rhinitis.
AB  - Allergic rhinitis manifests itself clinically due to the local release of
      mediators from activated cells within the nasal mucosa. Treatment strategies aim
      either to reduce the effects of these mediators on the sensory neural and
      vascular end organs, or to reduce the tissue accumulation of the activated cells
      that generate them. Corticosteroids intervene at a number of steps in the
      inflammatory pathway, and, by reducing the release of cytokines and chemokines,
      inhibit cell recruitment and activation. These effects are evident both in vivo
      and in vitro. While antihistamines also have some anti-inflammatory effects in
      vitro, these require higher concentrations than with corticosteroids and are not
      consistently reproduced in vivo. In addition, although antihistamines and
      corticosteroids might appear to have complementary mechanisms of action, clinical
      trials suggest that their co-administration does not confer any additional long
      term benefits compared with that achieved with corticosteroids alone. Topical
      corticosteroids are therefore the preferred anti-inflammatory therapy for
      persistent allergic rhinitis.

PMID- 10929864
TI  - Do intranasal corticosteroids affect childhood growth?
AB  - Topical intranasal corticosteroids (INS) are the most effective treatment for
      allergic rhinitis and are being increasingly prescribed to children. Due to the
      potent inhibition of childhood growth seen with oral corticosteroids, it is
      important to examine whether INS could have similar effects. The evidence
      available suggests that some INS, such as beclomethasone dipropionate (BDP), may
      slow growth when used regularly for prolonged periods. However, newer INS such as
      fluticasone propionate (FP) and mometasone furoate, which have substantially
      reduced bioavailability via gastrointestinal absorption, are unlikely to do so.
      Well-designed prospective studies are needed to distinguish those INS with
      reduced or absent effects on growth. In practice, choosing an INS which optimises
      the ratio of therapeutic effect to systemic bioavailability will probably reduce
      the risk of growth suppression to a negligible level.

PMID- 10929865
TI  - Other anti-inflammatory uses of intranasal corticosteroids in upper respiratory
      inflammatory diseases.
AB  - Topical corticosteroids are an effective treatment for nasal polyposis and other
      conditions associated with rhinitis. There is evidence that asthma, otitis media
      with effusion, and acute sinusitis may all benefit from such therapy. Fluticasone
      propionate (FP) drops have been shown to reduce polyp size, and to improve nasal
      inspiratory flow, while avoiding the side-effects of, for example, topical
      betamethasone therapy. In small children with allergic rhinitis, fluticasone
      propionate aqueous nasal spray (FPANS) has been shown to be significantly more
      effective than ketotifen in relieving night and daytime symptoms, and nasal
      blockage. There is also preliminary evidence of efficacy in obstructive sleep
      apnoea and acute sinusitis. The advent of FP, with its low propensity to cause
      systemic side-effects, makes it possible to use topical corticosteroid therapy
      safely for prolonged periods to treat many inflammatory diseases of the upper
      respiratory tract.

PMID- 10929866
TI  - An immunohistochemical study of matrix molecules associated with barrier membrane
      mediated periodontal wound healing.
AB  - Guided tissue regeneration (GTR) is a clinical procedure developed to facilitate
      periodontal regeneration by using barrier membranes to selectively promote the
      repopulation of a periodontal defect by periodontal ligament and bone cells at
      the expense of epithelial and gingival connective tissue cells. The aim of this
      study was to gain insight into the biological events occurring during membrane
      mediated periodontal wound healing by examining the immunohistochemical
      expression of a number of extracellular matrix components in tissues treated via
      the GTR technique. Experimental periodontal defects were created around the
      second premolar tooth in 4 dogs and wound closure was achieved by application of
      expanded polytetrafluoroethylene membranes around each tooth and flap positioning
      coronal to the cementoenamel junction. The dogs were sacrificed after a 4-wk
      healing period, block dissections of the part of the mandible containing the
      experimental tooth were obtained and paraffin sections were prepared. Using
      standard immunohistochemical techniques, the sections were stained with a
      monoclonal antibody against bone morphogenetic proteins 2 and 4 (BMP-2 and -4)
      and polyclonal antibodies against collagen I, collagen II, decorin, biglycan,
      bone sialoprotein, osteopontin and osteocalcin. Collagen I was predominantly
      localized within the regenerating bone, whereas collagen III staining was more
      abundant in the soft connective tissues of the defect. Decorin and biglycan
      staining was faint within the extracellular matrix of the regenerating defect,
      although both proteoglycans exhibited intense intracellular localization within
      some of the cells inhabiting the defect. The staining for BMP-2 and -4 was weak
      within the bone but strong within the extracellular matrix of the regenerating
      soft tissue. Osteopontin and bone sialoprotein were strongly localized in the
      regenerating bone and cementum found within the defect. Osteocalcin staining was
      present in both the regenerating and mature cementum and associated
      cementoblasts, and it was relatively weaker in the regenerating bone compared to
      the mature bone. The observed pattern of immunolocalization of the extracellular
      matrix macromolecules suggests that the heterogeneous cell population filling the
      GTR wound had created an environment that was conducive to periodontal
      regeneration.

PMID- 10929867
TI  - Despite large-scale T cell activation, only a minor subset of T cells responding
      in vitro to Actinobacillus actinomycetemcomitans differentiate into effector T
      cells.
AB  - Recent studies in our laboratory have demonstrated that Actinobacillus
      actinomycetemcomitans has a potent T cell stimulatory effect, activating more
      than half of all T cells. However, since the fate of these activated T cells was
      not known, the present study sought to determine whether all of these T cells
      differentiate into effector cells. To that end, the intracellular expression of T
      cell cytokines (IL-2, IFN-gamma, IL-4 and IL-10) in response to A.
      actinomycetemcomitans was determined by flow cytometry. Results demonstrated a
      time-dependent increase in the expression of the cytokines, most reaching peak
      levels at 24-48 h. At 48 h, the proportion of T cells expressing each of the
      cytokines were as follows: IL-2 (1.7%+/-0.3), IFN-gamma (1.8%+/-0.5), IL-4
      (1.0%+/-0.2) and IL-10 (1.5%+/-0.5). These data indicated that only 2-5% of all T
      cells stimulated with A. actinomycetemcomitans expressed any T cell cytokines.
      The finding of large-scale T cell activation in the absence of cytokine
      expression suggests that the activation of T cells in response to A.
      actinomycetemcomitans is incomplete. To investigate this phenomenon, peripheral
      blood mononuclear cells (PBMC) were cultured with A. actinomycetemcomitans for 24
      h followed by sorting of the activated (CD69+) cells by immunomagnetic separation
      and restimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin.
      Results demonstrated that nearly 90% of the T cells were unresponsive to further
      restimulation. A possible explanation for this unresponsiveness is the induction
      of clonal anergy among the responding T cells. To determine possible preferential
      effects of the stimulation on specific cytokines, the expression of each cytokine
      among T cells responding to A. actinomycetemcomitans was compared to the maximum
      levels achieved by PMA + ionomycin stimulation. Results showed that number of IL
      2+ and IFN-gamma+ T cells observed in response to A. actinomycetemcomitans were
      between 2% and 7% of those seen in response to PMA + ionomycin. Conversely, the
      proportions of T cells expressing IL-4 or IL-10 were between 35% and 90% of those
      following stimulation with PMA + ionomycin. Hence, A. actinomycetemcomitans
      appears to more preferentially induce T cells expressing IL-4 and IL-10.
      Collectively, these data suggest that the in vitro stimulation of T cells with A.
      actinomycetemcomitans leads to partial activation, i.e. only a minor subset of T
      cells responding to A. actinomycetemcomitans differentiate into effector cells,
      while a significant proportion become unresponsive to restimulation, suggesting
      clonal anergy.

PMID- 10929868
TI  - C5a modulation of interleukin-1 beta-induced interleukin-6 production by human
      osteoblast-like cells.
AB  - Periodontal bone resorption is controlled by osteoblast products, including
      interleukin (IL)-6, which are stimulated by other cytokines and complement
      components in the pro-inflammatory milieu. This study demonstrated that human
      osteoblast-like osteosarcoma cells (MG-63) responded to human recombinant (hr)
      C5a by releasing significant amounts of the bone-resorbing cytokine IL-6. C5a
      induced release of IL-6 was enhanced 330% when cells were exposed to IL-1beta
      prior to C5a challenge at optimal concentrations (1.0 microg/ml C5a, 0.1 ng/ml IL
      1beta). Cells simultaneously challenged with these concentrations of C5a and IL
      1beta produced a 700% increase in IL-6 release relative to cells challenged with
      IL-1beta alone. Incubation of IL-1beta-treated cells with anti-human C5a receptor
      (C5aR) Ab resulted in a 78% suppression of the C5a-induced release of IL-6, but
      C5aR neutralization did not affect C5a/IL-1beta co-stimulation of IL-6. In
      addition, neither IL-1beta nor C5a significantly altered the other's cell-surface
      receptor relative to binding affinity or density. These results indicate that
      while MG-63 cells express functional C5aRs, the synergistic effect of C5a and IL
      1beta on osteoblast IL-6 production is probably controlled by post-receptor
      signaling events. C5a agonists and antagonist used to alter critical C5a
      concentrations may present a new point of therapeutic intervention for the
      treatment of inflammatory bone resorption such as is found in periodontitis.

PMID- 10929869
TI  - Expression and activity of thrombomodulin in human gingival epithelium: in vivo
      and in vitro studies.
AB  - Epidermal keratinocytes thrombomodulin (TM) has been shown to regulate thrombin
      at sites of cutaneous injury in addition to a role for epidermal differentiation.
      TM, a major anticoagulant proteoglycan of the endothelial cell membrane, is a
      thrombin receptor that acts as a co-factor for protein C activation. Thrombin has
      pro-inflammatory effects for periodontitis. However, little is known about TM in
      gingival tissue with periodontitis. We used immunohistochemistry to examine
      expression of TM in gingival epithelium from patients with periodontitis. In
      vitro, we observed TM expression at varying Ca2+ concentrations by confocal laser
      scanning microscopy, examined the expression of TM mRNA and tested TM co-factor
      activity. Furthermore, we measured TM concentration in gingival crevicular fluid
      (GCF) from 11 severe adult cases of periodontitis using enzyme-linked
      immunosorbent assay. Immunoreactive TM was present in gingival epithelium and
      junctional epithelium, and was reduced in inflamed gingival epithelium compared
      to healthy gingival epithelium. Ultrastructurally, TM, including microvilli, was
      observed on the cell membrane. TM localization in cells cultured in 0.09 mM Ca2+
      differed from that in cells exposed to 1.2 mM Ca2+. Northern analysis
      demonstrated TM mRNA in gingival keratinocytes more than in human umbilical vein
      endothelial cells (HUVEC). Gingival keratinocytes also facilitated protein C
      activation by thrombin, although less strongly than HUVEC. TM in GCF at sites
      with bleeding on probing in patients was significantly elevated (p < 0.001,
      Student's t-test). TM in gingival epithelium may regulate thrombin activity at
      sites of coagulation and inflammation with periodontal disease, although
      inflammation may impair this regulation of thrombin.

PMID- 10929870
TI  - Human gingival glycosaminoglycans in cyclosporin-induced overgrowth.
AB  - Glycosaminoglycans in normal and cyclosporin-induced gingival overgrowth were
      extracted by papain digestion and purified by Mono Q-FPLC chromatography. The
      purified glycosaminoglycans were analyzed by agarose gel electrophoresis and by
      the pattern of degradation products formed by chondroitin lyases on HPLC
      chromatography. Our results on the glycosaminoglycan composition showed presence
      of chondroitin 4- and 6-sulfate, dermatan sulfate, heparan sulfate and hyaluronic
      acid in both normal gingiva and cyclosporin-induced gingival overgrowth. The
      total and relative amounts of glycosaminoglycans were similar between normal and
      overgrown gingiva. This suggests that the glycosaminoglycan composition is not
      changed in cyclosporin-induced gingival overgrowth. Our present biochemical
      results conflict with histochemical and biosynthetic data previously reported by
      other groups. Those studies suggested that the affected tissues contained higher
      levels of glycosaminoglycans and that cyclosporin induced comparably high levels
      of these compounds in in vitro cultures of gingival fibroblasts. Therefore, these
      discrepant results suggest that a cyclosporin-induced increase on gingival
      glycosaminoglycans still remains an open question. The implications of these
      conflicting results are discussed.

PMID- 10929871
TI  - Expression of Tie-2, angiopoietin-1, angiopoietin-2, ephrinB2 and EphB4 in
      pyogenic granuloma of human gingiva implicates their roles in inflammatory
      angiogenesis.
AB  - Tie-2, angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), ephrin-B2 and Eph-B4 are
      all important vascular morphogenesis factors which exhibit their functions in
      angiogenesis and blood vessel remodeling in embryonic stage. However, their roles
      in post-natal inflammatory angiogenesis are still unclear. Pyogenic granuloma is
      a benign inflammatory lesion that mostly occurs on the gingiva of females with
      high levels of steroid hormones. Prominent capillary growth in hyperplastic
      granulation tissue is characteristic histopathologically in pyogenic granuloma.
      The purpose of this study was to detect and compare the expressions of Tie-2, Ang
      1, Ang-2, ephrin-B2 and Eph-B4 among pyogenic granuloma on human gingiva, gingiva
      diagnosed with periodontitis and healthy gingiva by immunohistochemistry. The
      immunostaining revealed that all of the endothelial cells and some mesenchymal
      cells expressed Tie-2. The cells which expressed Ang-1 and Ang-2 were mainly
      macrophage- or monocyte-like mesenchymal cells and smooth muscle cells
      surrounding blood vessels. The expression of ephrin-B2 and Eph-B4 was not
      exclusively limited to the endothelial cells of arteries and veins, respectively,
      as in mice embryo. Eph-B4 was expressed in the endothelial cells of newly budding
      capillaries and venules while ephrin-B2 was expressed in macrophage-like
      mesenchymal cells. Some of the ephrin-B2 positive cells were in direct contact
      with endothelial cells. The statistical analysis demonstrated that all of the
      five factors were upregulated in pyogenic granuloma compared to healthy gingiva.
      In conclusion, the 5 polypeptides mentioned above may play important roles in the
      process of adult inflammatory neovascularization, especially in pyogenic
      granuloma. It is highly plausible that most of the new capillaries in
      inflammatory angiogenesis originated from venules instead of arterioles.

PMID- 10929873
TI  - Complicated urinary tract infections.
AB  - The term complicated urinary tract infection is usually used to convey an
      infection that occurs in a patient with a structural or functional abnormality
      impeding urine flow, or in a host with altered defences. The distinction between
      complicated and uncomplicated infections is important because, when complicating
      factors are present, antimicrobial resistance is more common and the response to
      therapy is often disappointing, even with agents active against the causative
      microbial pathogen. In addition, severe complications frequently occur which may
      lead to urosepsis, renal scarring or even end-stage disease. Drug treatment of
      complicated urinary tract infections often must be complemented with endoscopic
      and/or surgical intervention. Only a few well designed treatment studies have
      been published and therefore sources for definitive therapeutic guidelines remain
      inadequate.

PMID- 10929872
TI  - Effect of the interleukin-1 genotype on monocyte IL-1beta expression in subjects
      with adult periodontitis.
AB  - An association has been reported between polymorphisms in the genes encoding IL
      1alpha (-889) and IL-1beta (+3953) (periodontitis susceptibility trait, PST), and
      an increased severity of periodontitis (18). The IL-1beta polymorphism was
      reported to correlate with increased IL-1beta expression by monocytes in response
      to bacterial stimulants. In the present study, we determined if PST positive
      subjects with periodontitis exhibit elevated production of IL-1beta, compared to
      PST negative periodontitis patients. Peripheral blood monocytes were obtained
      from 10 PST+ and 10 PST- age- and disease-balanced subjects with adult forms of
      periodontitis. Monocytes were cultured with a panel of bacterial stimulants,
      including Escherichia coli and Porphyromonas gingivalis LPS, and whole
      formalinized periodontal pathogens P. gingivalis, Bacteroides forsythus and
      Prevotella intermedia, and health-associated organisms Veillonella parvula and
      Streptococcus sanguis. Our results demonstrate that monocytes from PST+ and PST-
      patients showed no significant differences in IL-1beta production in response to
      any stimulant tested. In addition, the periodontal pathogens P. gingivalis, B.
      forsythus and P. intermedia failed to stimulate higher IL-1beta responses
      compared to health-associated species V. parvula and S. sanguis. A marked
      interindividual variation in production of IL-1beta was seen, with high, low and
      intermediate responders present in both PST+ and PST- groups. We conclude that
      genetic loci other than the PST polymorphisms are also important regulators of
      monocyte IL-1 responses.

PMID- 10929874
TI  - High-level amikacin resistance in Pseudomonas aeruginosa associated with a 3'
      phosphotransferase with high affinity for amikacin.
AB  - This work describes the characterization of the phosphotransferase enzymatic
      activity responsible for amikacin resistance in two clinical Pseudomona
      aeruginosa strains, isolated from a hospital that used amikacin as first-line
      aminoglycoside. Amikacin-resistant P. aeruginosa PA40 and PA43 (MIC: 128 mg/l)
      were shown to have APH activity with a substrate profile similar to that of
      APH(3')-VI. The enzyme from P. aeruginosa PA40 was purified to > 70% homogeneity.
      The Km of amikacin for this enzyme was 1.4 microM, the Vmax/Km ratio for amikacin
      was higher than for the other aminoglycosides tested and PCR and DNA sequencing
      ruled out the presence of aph(3')-IIps. Amikacin resistance in this strain was,
      therefore, associated with APH(3')-VI and the high affinity of this enzyme for
      amikacin could explain the high-level resistance that we observed.

PMID- 10929875
TI  - Distribution and antibiotic resistance of isolates from lower respiratory tract
      and blood cultures from patients in three Italian intensive care units: a 2-year
      comparison.
AB  - The distribution and antibiotic resistance of major pathogens isolated from
      patients in ICUs were studied by three Italian microbiological laboratories.
      Consecutive aerobic strains were collected over two different time periods from
      protected brushing bronchoscopy, broncho-alveolar lavage and blood cultures. A
      total of 420 strains were isolated during the first period (47.3% gram-negative
      and 52.7% gram-positive) and 412 over the second period (50.5% gram-negative and
      49.5% gram-positive). Pseudomonas aeruginosa was the most frequently isolated
      organism from the respiratory tract followed by Staphylococcus aureus.
      Methicillin resistance was 47.9 and 44.5% in S. aureus and 63.0 and 65.1% in
      coagulase-negative staphylococci over the two periods. No glycopeptide-resistance
      was found in gram-positive organisms. Ceftazidime-resistance in Klebsiella
      pneumoniae was very high.

PMID- 10929876
TI  - In vitro activity of ceftiofur tested against clinical isolates of Escherichia
      coli and Klebsiella pneumoniae including extended spectrum beta-lactamase
      producing strains.
AB  - In vitro activity of ceftiofur, a cephalosporin used in veterinary practice was
      compared using ceftriaxone-resistant (producing extended spectrum beta-lactamase
      (ESBL)) and -susceptible clinical isolates of Esherichia coli and Klebsiella
      pneumoniae. The ceftriaxone-susceptible isolates exhibited a lower range of
      ceftiofur MICs (MIC50, 0.5 mg/l, MIC90 1.0 mg/l). Those isolates known to produce
      an ESBL were also resistant to ceftiofur (MIC50, > or = 32 mg/l). The latter
      isolates were also less susceptible to other comparator drugs (cefquinome,
      gentamicin and trimethoprim/sulphamethoxazole) in contrast to the ceftriaxone
      susceptible strains. The clinical isolates showed high correlation between
      ceftriaxone and ceftiofur MICs (y = 2.6 + 0.89x, r = 0.95). Using the current
      ceftiofur susceptible breakpoint (< or = 2 mg/l) used for veterinary practice
      (respiratory tract pathogens), the ESBL-producing strains of E. coli and K.
      pneumoniae could be accurately separated from susceptible strains. This ceftiofur
      breakpoint MIC corresponds to the National Committee for Clinical Laboratory
      Standards ESBL screening concentration for ceftriaxone set at < or = 1 mg/l =
      negative for ESBL production. Ceftiofur was also observed to be very active in
      vitro against ampicillin-resistant, non-ESBL producing enteric isolates. This new
      cephem appears to be very potent against the tested Enterobacteriaceae and of
      potential wide clinical veterinary utility.

PMID- 10929877
TI  - Helicobacter pylori: ureA, cagA and vacA expression during conversion to the
      coccoid form.
AB  - As viability of coccoid forms of Helicobacter pylori can only be verified by
      demonstrating the integrity of the DNA and active protein synthesis, we analysed
      the expression of ureA, cagA, vacA genes after prolonged incubation in a liquid
      medium. Exponentially growing and ageing phase cultures were used. Our results
      showed that, although the coccoid forms had decreased DNA and RNA levels after 31
      days, they were not degraded and still expressed the urease, cytotoxic island and
      vacuolating toxin genes. Coccoid forms are therefore viable and may act as a
      transmissible agent that plays a crucial role in disease relapses after
      antibiotic therapy.

PMID- 10929878
TI  - The effect of ferrous sulphate and sucralfate on the bioavailability of oral
      gemifloxacin in healthy volunteers.
AB  - Sucralfate is a cytoprotectant with antacid properties and ferrous sulphate is
      commonly prescribed for iron-deficiency anaemia. This open, randomized, single
      dose, five-way crossover study investigated the effect of sucralfate and ferrous
      sulphate on the bioavailability of gemifloxacin, a novel fluoroquinolone
      antimicrobial. Twenty-seven healthy male volunteers received gemifloxacin, 320 mg
      p.o., alone, 3 h after sucralfate (2 g) or ferrous sulphate (325 mg), or 2 h
      before sucralfate or ferrous sulphate. Each subject received all five dosing
      regimens in random order with at least 6 days between regimens. Plasma samples
      collected up to 48 h after dosing with gemifloxacin, were assayed for
      gemifloxacin to determine pharmacokinetic parameters. Administration of
      gemifloxacin 3 h after sucralfate produced a marked decrease of 53% in the area
      under the plasma concentration-time curve from time zero extrapolated to infinity
      (AUC0-infinity), and a decrease of 69% in the maximal plasma concentration
      (Cmax). Administration of gemifloxacin 3 h after ferrous sulphate resulted in
      only a modest reduction of 11% in AUC0-infinity and of 20% in Cmax, which was not
      considered to be clinically significant. In contrast, at the doses used neither
      sucralfate nor ferrous sulphate altered gemifloxacin bioavailability when it was
      administered 2 h before either of these agents. Gemifloxacin was well tolerated
      in all the regimens. The results of this study support the dosing recommendation
      that gemifloxacin can be safely administered at least 2 h before sucralfate or
      ferrous sulphate, or at least 3 h after ferrous sulphate.

PMID- 10929879
TI  - Evaluation of quinupristin/dalfopristin (Synercid) and RPR 106972 stability in
      susceptibility testing media.
AB  - In response to conflicting reports on the chemical stability of
      quinupristin/dalfopristin, a study was designed to assess the in vitro longevity
      and effects of media and storage conditions on this streptogramin combination.
      Broth microdilution trays containing parenteral (quinupristin/dalfopristin) and
      oral (RPR 106972) streptogramin combinations as well as pristinomycin components
      (P-I and P-II) were preincubated at 35 degrees C for 12-72 h before inoculation
      with control strains (Streptococcus pneumoniae ATCC 49619, Haemophilus influenzae
      ATCC 49247, Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 29213)
      and five clinical isolates with various drug resistance phenotypes. Overall, the
      mean quinupristin/dalfopristin activity loss was 24%/12 h, 41%/18 h, 43%/24 h,
      69%/48 h and 79%/72 h with no detected loss of potency when measured by E.
      faecalis until 18 h. RPR 106972 mean activity loss was 6%/12 h, 19%/18 h, 19%/24
      h, 56%/48 h and 71%/72 h with no loss of potency as measured by S. aureus until
      48 h. Overall, P-I components had greater stability as compared with P-II for
      both drug combinations. Bioassays showed similar trends in decreased activity.
      Bioassay differences among media types were only significant (> 3 mm; greater
      loss of potency) for haemophilus test media for both P-II components at 72 h. The
      presence of an organism in the medium had no effect on stability assay results.
      The effect of storage temperature (4, 25 degrees C) on quinupristin/dalfopristin
      and RPR 106972 stability was also detrimental to drug potency indicating the
      requirement for rigid quality assurance for streptogramin diagnostic reagents
      when determining activity by reference or standardized susceptibility tests.

PMID- 10929880
TI  - Antimicrobial and cancer cell growth inhibitory activities of 3beta-acetoxy
      17beta-(L-prolyl)amino-5alpha-androstane in vitro.
AB  - The in vitro activity of the steroidal amide 3beta-acetoxy-17beta-(L-prolyl)amino
      5alpha-androstane against 179 gram-positive clinical isolates was examined. The
      minimum bactericidal concentration (MBC)/MIC ratios were < or = 2 for 73% of
      methicillin-resistant Staphyllococcus aureus, 59% of vancomycin-resistant
      Enterococcus spp. and 88% of penicillin-resistant Streptococcus pneumoniae. The
      androstane derivative was bactericidal for a variety of other gram-positive
      genera, including Nocardia, Corynebacterium and Listeria. Variation in MICs is pH
      6-8 media was slight. The frequency of occurrence of bacterial spontaneous
      mutations to resistance ranged from 10(-6) to 10(-9). Kill curve analysis
      confirmed the bactericidal nature of the steroidal amide, and demonstrated that
      killing was time dependent but not concentration dependent for all organisms. The
      ability of 3beta-acetoxy-17beta-(L-prolyl)amino-5alpha-androstane to inhibit
      human cancer cell growth was also evaluated. The concentration required to
      inhibit 50% of cell growth (GI50) was < 2.5 mg/l for all cell lines examined. In
      single-dose murine toxicity evaluations, the androstane derivative was non-toxic
      at doses up to 400 mg/kg.

PMID- 10929881
TI  - Antibacterial activity of four dentin bonding systems.
AB  - The antibacterial action of bonding systems Gluma 2000, Syntac, Prisma Universal
      Bond 3, Scotchbond Multipurpose and Prime-Bond was tested against 32 strains of
      the caries-producing bacteria Streptococcus spp., Lactobacillus spp., Actinomyces
      spp., Porphyromonas spp. and Clostridium spp. An agar plate diffusion method was
      used with chlorhexidine as the positive control. Assays were performed in
      triplicate for each component (primer and adhesive) of the bonding systems. All
      the adhesives were found to inhibit bacterial growth but with differences in
      their spectra of action. The sum action of the Scotchbond Multipurpose components
      were most inhibitory and Prime-Bond was found to be the least effective system.

PMID- 10929882
TI  - Antibiotic resistance in bacteria of animal origin: methods in use to monitor
      resistance in EU countries.
AB  - A study on the ongoing monitoring programmes in 13 European countries was made as
      part of a concerted action funded by the European Commission. Five main reference
      systems were used in the surveyed countries and three categories of bacteria were
      monitored, zoonotic agents, indicator bacteria and veterinary pathogens. The five
      reference systems and an overview of the national monitoring programmes are
      described. Differences exist and there is a real need for standardisation at the
      European level. This harmonisation could be set up both for microbiological
      methods and the epidemiological results derived from common methods. Disk
      diffusion methods are most widely used and many of the monitored species and
      control strains are similar in the action's participating countries.

PMID- 10929883
TI  - The recognition of proteins and peptides by antibodies.

PMID- 10929884
TI  - Nature of specific ligand-receptor bonds, in particular the antigen-antibody
      bond.

PMID- 10929885
TI  - Precipitation and agglutination.

PMID- 10929886
TI  - Enzyme-linked immunosorbent assay.

PMID- 10929887
TI  - Determination of antibody affinity.

PMID- 10929888
TI  - Immunofluorescence and enzyme immunomicroscopy methods.
AB  - Immunohistochemistry is a very versatile immunopathological tool for the study of
      distribution and differentiation of antigens and of the presence of in vivo-bound
      immune complexes. In addition, these methods are invaluable for detection of
      circulating antibodies to the various antigens. Such methods may be the only ones
      of choice in certain situations. For the detection and quantitation of these
      antigens, it is very essential that the immunohistochemical methods for detecting
      them are properly standardized, with the inclusion of appropriate controls.

PMID- 10929889
TI  - Multiparameter flow cytometry.

PMID- 10929890
TI  - Immunoblotting, dot-blotting, and ELISPOT assays: methods and applications.

PMID- 10929891
TI  - How do we offer clinical relief to patients with gastro-oesophageal reflux
      disease?
AB  - In gastro-oesophageal reflux disease (GORD), the majority of patients are
      endoscopy negative. However, symptoms can affect the quality of life irrespective
      of the presence of oesophagitis. Proton pump inhibitors (PPIs) are far more
      effective than H2 receptor antagonists (H2RAs) or prokinetics with regard to the
      speed of symptom relief. Despite this undisputed progress, there is some conflict
      on whether symptoms should be managed until full resolution in endoscopy-negative
      patients or in those with mild oesophagitis. Considering that GORD is not a life
      threatening condition, some authorities admit that patients should accept minimal
      residual symptoms. They argue that PPIs are expensive while healthcare resources
      are limited, and that long-term safety of PPIs has not been completely
      established. Moreover, they underline that many patients do not seek medical help
      and are satisfied with self-medication (with antacids/alginates or even over-the
      counter H2RAs). On the other hand, some clinicians prefer a full resolution of
      symptom strategy because this is now achievable with modern PPIs without serious
      concerns in terms of tolerance and safety. Indeed, quality of life is rapidly
      restored by PPIs. Moreover, symptom relief by PPIs is highly predictive of
      healing, making endoscopic control unnecessary at least for mild/moderate
      oesophagitis. Finally, there is also some controversy over whether we should
      start treatment with PPIs or use less potent drugs as first-line therapy. If one
      considers not only the direct cost of drugs, but also the indirect ones (e.g.
      sick leave days), it is reasonable to think that PPIs may be more cost-effective
      than H2RAs or prokinetics, at least when the disease is of moderate or severe
      intensity. In conclusion, with modern PPIs like lansoprazole, rapid and full
      resolution of symptoms is now achievable in the large majority of patients.

PMID- 10929892
TI  - Should we eradicate Helicobacter pylori in patients with recurrent gastro
      oesophageal reflux disease?
AB  - The 1998 Guidelines of the American College of Gastroenterology recommend that
      diagnostic testing for Helicobacter pylori infection should only be performed if
      treatment is intended, and that testing for H. pylori is not indicated in
      patients on long-term treatment with a proton pump inhibitor (PPI) for gastro
      oesophageal reflux disease (GORD). Moreover, a recent evidence-based workshop
      evaluating major clinical strategies for the management of GORD reported, with an
      'A' category (maximum of evidence), that eradication of H. pylori does not heal
      or prevent relapse of GORD. In detail, it seems that H. pylori infection per se
      has no effect on the pathogenic mechanisms determining either reflux or its
      complications. The relationship between H. pylori and oesophagitis is mediated by
      the effect of H. pylori on gastric acid secretion; in particular, by the proximal
      extension of gastritis and related impairment of gastric secretory function. In
      general, if the corpus is infected, the amount of acid available for reflux is
      less and the probability of excessive oesophageal acid exposure leading to
      oesophagitis reduced. However, the clinical relevance of corpus H. pylori
      infection as a biological antisecretory agent (and of H. pylori eradication)
      seems small or absent, at least in the long run. Conversely, the previous claim
      of an increased risk of atrophic gastritis in H. pylori-infected patients treated
      long term with PPI drugs appears not to be confirmed by subsequent studies. In
      conclusion, H. pylori infection may, in some circumstances, be moderately
      favourable and, in other circumstances, it may be neutral, with respect to the
      management of GORD.

PMID- 10929893
TI  - Who needs prophylaxis of nonsteroidal anti-inflammatory drug-induced ulcers and
      what is optimal prophylaxis?
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) are used successfully by many
      patients for the treatment of the signs and symptoms of arthritis, and other
      painful and inflammatory disorders. However, traditional nonselective NSAIDs that
      inhibit COX-1 and COX-2 lead to a state of propensity for gastric and duodenal
      ulcer disease and ulcer complications. The point prevalence of endoscopic ulcers
      ranges from 14 to 44% of patients using NSAIDs. Moreover, it is estimated that
      1.46-1.90% of chronic NSAID users develop serious upper gastrointestinal (UGI)
      toxicity annually, most notably UGI bleeding, gastric/duodenal obstruction or
      ulcer perforation. In the USA, it has been estimated that 107,000
      hospitalisations and 16,500 deaths occur annually related to the use of
      nonselective NSAIDs. Because these ulcer complications are often not heralded by
      chronic symptoms of dyspepsia, symptoms alone are not sufficient to guide long
      term management of NSAID-related toxicity. Instead, prophylactic and preventive
      therapies are recommended in patients at above-average and high risk.
      Epidemiological data have identified that patients with a past history of ulcer
      disease, past history of UGI bleeding, greater age, concomitant corticosteroid
      use, and those who use higher doses and multiple NSAIDs fall into this category.
      Other risk factors of lesser importance have also been identified. A
      controversial issue remains regarding the possible increased risk of NSAID
      associated ulcers and ulcer complications in patients who are infected with
      Helicobacter pylori. Prophylactic therapies have been evaluated primarily in
      randomised clinical trials, with the rate of endoscopic ulcers as the primary
      endpoint. It is assumed, but not proven, that these endoscopic ulcer rates are
      surrogate markers for gastrointestinal toxicity and are predictive of the rate of
      significant UGI adverse events. In the only outcomes trial to date, it was
      reported that misoprostol (200 microg 4 times daily) caused an approximately 50%
      reduction in serious UGI adverse events in a large 6-month trial involving
      rheumatoid arthritis patients. In parallel, this approximates the 50% reduction
      of endoscopic ulcers seen in randomised controlled trials using misoprostol.
      While H2 receptor antagonists are ineffective agents at traditional doses, proton
      pump inhibitors have been clearly shown to reduce the rate of endoscopic ulcers
      in several trials. In fact, the efficacy approximates to the efficacy seen with
      misoprostol. Beyond efficacy and in practical terms, the choice of optimal
      prophylaxis should take into consideration patient compliance, patient
      satisfaction, side-effects and cost.

PMID- 10929894
TI  - What consideration should be given to Helicobacter pylori in treating
      nonsteroidal anti-inflammatory drug ulcers?
AB  - Although Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs)
      both cause peptic ulcers, they do so by different mechanisms so any interaction
      is not necessarily harmful. H. pylori has been shown to enhance gastric mucosal
      prostaglandin synthesis, while NSAIDs suppress it Pragmatically, there is no
      compelling evidence in favour of H. pylori eradication in all patients who take
      NSAIDs. As a broad generalisation, in therapeutic studies of NSAID users, those
      who have no ulcer at trial entry are more prone to ulcer development if they are
      H. pylori-positive. By contrast, in those who have ulcers at baseline, H. pylori
      positive individuals are less likely to develop ulcers, particularly if taking
      acid-suppressive therapy. Trials of H. pylori eradication therapy tend to
      replicate this dichotomy. In one study of patients starting NSAIDs for the first
      time, with no ulcer history and no baseline ulcer, use of bismuth-based
      eradication therapy was associated with a lower incidence of gastric ulcer at 2
      months. Conversely, in a study of patients with endoscopically proven ulcers
      and/or troublesome dyspepsia, proton pump inhibitor based eradication treatment
      had no effect on outcome (of acid suppression) over 6 months. H. pylori
      eradication has been associated with significantly slower healing of gastric
      ulcers compared with patients who did not undergo eradication. However, the
      effect of H. pylori eradication on healing of NSAID-associated duodenal ulcers
      does not appear to be so dramatic, and limited evidence suggests that it may be
      possible to prevent H. pylori-associated duodenal ulcer by eradicating the
      infection. An evidence-based approach to treatment would suggest that NSAID users
      should undergo H. pylori eradication therapy if they have a duodenal ulcer,
      whether or not they continue NSAIDs. Because COX-2 inhibitors appear not to be
      ulcerogenic, management of H. pylori in patients taking these drugs can be based
      upon the same risk assessment as in patients not taking anti-arthritis drugs. H.
      pylori eradication should not be used universally or in high-risk gastric ulcer
      patients who require management with acid suppression.

PMID- 10929895
TI  - Practice and principle: the influence of current research on our management of
      acid-related disorders. Summary: key messages.

PMID- 10929896
TI  - Long-term effects of Helicobacter pylori eradication on gastric antral mucosa in
      duodenal ulcer patients.
AB  - OBJECTIVES: The aim of this study was to assess the consequences of prolonged
      Helicobacter pylori eradication on gastric antral mucosa in duodenal ulcer
      patients. PATIENTS AND METHODS: Forty-three duodenal ulcer patients with
      confirmed H. pylori eradication after one year of follow-up were included in this
      retrospective study. Before H. pylori eradication and during the follow-up, four
      antral prepyloric biopsy samples were taken for histopathological examination and
      culture. Histopathological lesions were graded semi-quantitatively according to
      the updated Sydney System for activity, chronic inflammation, glandular atrophy
      and intestinal metaplasia (IM), as well as presence of lymphoid follicles.
      RESULTS: After a mean follow-up of 43 +/- 23 months, H. pylori eradication
      statistically improved all gastritis scores, including the atrophy score and the
      lymphoid follicle score but excluding the IM score. H. pylori eradication
      resulted in normalization of gastric mucosa in 51.2% of patients and a
      significantly lower proportion of patients with non-atrophic gastritis and
      atrophic gastritis without IM. Atrophy totally disappeared in 16/29 patients
      (55.2%) in whom IM was absent. No predictive factor for regression of atrophy or
      normalization of gastric mucosa was identified. CONCLUSION: In duodenal ulcer
      patients, prolonged absence (more than one year) of H. pylori can lead to
      normalization of the antral mucosa and the disappearance of mucosa-associated
      lymphoid tissue, as well as the regression of antral atrophy. Long-term studies
      involving selected patients with atrophy and IM which persist after H. pylori
      eradication are needed to determine the potential benefits of treating H. pylori
      gastritis with regard to gastric cancer prevention.

PMID- 10929897
TI  - Prospective evaluation of a whole-blood antibody test (FlexPack HP) for in-office
      diagnosis of Helicobacter pylori infection in untreated patients.
AB  - OBJECTIVES: Rapid, reliable in-office tests are needed for applying the adopted
      screen-and-treat strategy in Helicobacter pylori-positive young dyspeptic
      patients. DESIGN: We have evaluated the performance characteristics of a whole
      blood antibody (WBA) test for the detection of H. pylori infection under in
      office conditions. METHODS: In a prospective double-blind study, 183 untreated
      patients referred to a tertiary centre for endoscopy because of dyspepsia were
      studied. Patients were defined as H. pylori-positive if two out of three tests
      (histology, rapid urease test, Gram staining of biopsy smears) were positive, and
      H. pylori-negative if all three tests were negative. An in-office test detecting
      IgG antibodies to H. pylori (FlexPack HP, Abbott Diagnostics) was used with
      capillary blood and compared with an ELISA detecting IgG (quantitative) and IgA
      (qualitative) H. pylori serum antibodies. RESULTS: Of the 183 patients, 139 were
      defined as H. pylori-positive. The in-office test had 79% sensitivity, 95%
      specificity, 98% positive and 59% negative predictive value. The respective
      values for IgG serum antibodies were 94, 70, 91 and 79% and those for IgA
      antibodies were 86, 82, 94 and 64%. About 50% of the false-negative in-office
      tests had a serum IgG antibody titre > 100 units. Co-evaluation of our data with
      published reports suggested that both the median sensitivity and negative
      predictive value of the kit are significantly inferior when performed with whole
      blood (five studies) compared with serum (nine studies) (82 versus 92% and 82
      versus 93% respectively, P < 0.035). CONCLUSIONS: Improvement of the performance
      characteristics of FlexPack HP in-office test is needed. However, the test may be
      a useful tool for identifying H. pylori-positive patients in younger age groups
      who could be managed without upper gastrointestinal endoscopy.

PMID- 10929898
TI  - Helicobacter pylori eradication prevents recurrence from peptic ulcer
      haemorrhage.
AB  - BACKGROUND: Successful eradication of Helicobacter pylori infection clearly
      modifies the natural history of peptic ulcer disease and prevents further
      recurrences of duodenal and gastric ulcers. However, there are few prospective
      studies about actual rates of rebleeding after H. pylori eradication, a highly
      relevant aspect of management as re-infection, relapse of ulcer disease for other
      reasons (i.e. anti-inflammatory agents) or idiopathic ulcers unrelated to H.
      pylori may develop and cause further bleeding episodes. OBJECTIVE: To determine
      the incidence of bleeding episodes after eradication of H. pylori infection in
      patients who had bled from an H. pylori-positive peptic ulcer. PARTICIPANTS AND
      INTERVENTIONS: H. pylori-positive patients who bled from a gastric or duodenal
      ulcer were treated with appropriate triple and/or quadruple therapy. H. pylori
      eradication was confirmed by urea breath test 4 weeks after treatment. Patients
      received no further treatment but were followed clinically and additional urea
      breath tests were performed every 6 months. Endoscopy with antral and corpus
      biopsies and urea breath test were repeated as soon as patients manifested any
      dyspeptic symptoms that might signal recurrence. RESULTS: A total of 103 patients
      with bleeding duodenal ulcer were included in the study; H. pylori was
      successfully eradicated in 93 of these patients, who were followed for a median
      interval of 27 months. The yearly re-infection rate was calculated to be 0.6%.
      There were no instances of rebleeding in any patients during the follow-up
      period. CONCLUSIONS: Even after prolonged follow-up, successful H. pylori
      eradication prevents rebleeding.

PMID- 10929899
TI  - Characteristics of secondary oesophageal peristalsis in operated and non-operated
      patients with chronic gastro-oesophageal reflux disease.
AB  - BACKGROUND AND AIMS: Secondary oesophageal peristalsis contributes to oesophageal
      volume clearance and may be impaired in a significant proportion of patients with
      chronic gastro-oesophageal reflux disease (GORD). This study aimed to investigate
      the triggering of secondary peristalsis in chronic GORD patients compared to
      those previously operated on with anti-reflux surgery. PATIENTS AND METHODS:
      Healthy volunteers, chronic GORD patients with proven oesophagitis and patients
      successfully operated on with anti-reflux surgery (> 3 years ago) were
      investigated. Secondary peristalsis was elicited by oesophageal distension by a
      bolus of air (10 ml) injected rapidly into the mid-portion of the oesophagus. The
      peristaltic characteristics in the distal oesophagus were assessed by use of
      stationary manometry. RESULTS: The primary peristaltic amplitude in the distal
      third of the oesophagus was significantly higher (P < 0.002) in the non-operated
      GORD cases than in those recruited for surgery. Furthermore, a difference in the
      frequency of failed primary peristalsis was revealed (2.1 versus 8.4%) between
      the non-operated and operated patients. Secondary peristalsis occurred in 65 +/-
      13.2% (mean +/- SE) of the healthy subjects on stimulation, which was a higher
      figure than in the GORD patients. In patients investigated after successful anti
      reflux surgery, a secondary peristaltic wave was elicited in only 26 +/- 7.2% of
      the attempts, which was significantly lower than the 46 +/- 7.7% seen in non
      operated GORD patients (P < 0.05). A direct comparison between motor
      characteristics of primary and secondary peristalsis revealed that the latter
      amplitudes were significantly lower both in the non-operated and in the operated
      cases (P < 0.005). CONCLUSIONS: The triggering of secondary peristalsis seems to
      be impaired in chronic GORD patients. Investigating similar patients > 3 years
      after successful anti-reflux surgery revealed an even lower prevalence of
      secondary peristaltic waves, implying persistence of the abnormality after
      surgery and consistent with other evidence that GORD is associated with a primary
      defect in oesophageal motor function.

PMID- 10929900
TI  - Prevalence and clinical features of heterotopic gastric mucosa in the upper
      oesophagus (inlet patch).
AB  - AIM: To determine the prevalence of heterotopic gastric mucosa in the upper
      oesophagus (inlet patch) and the factors that may influence its finding. To study
      its macroscopic and microscopic characteristics and its relationship with
      symptoms and oesophago-gastroduodenal diseases. PATIENTS AND METHODS: The study
      was carried out in two different prospective series of consecutive patients
      undergoing oesophagogastroduodenoscopy. The first 791 patients were examined by
      one medical practitioner who was aware of the existence of inlet patch entity and
      aimed to evaluate the prevalence of inlet patch. The second series of 687
      patients was examined by another investigator who was aware of the existence of
      inlet patch entity and who was requested to refer all patients with inlet patch,
      but he was unaware of the existence of a study aimed at evaluating the prevalence
      of inlet patch. The heterotopic gastric mucosal patches identified in the upper
      oesophagus were photographed, biopsied and analysed according to the Sydney
      system score. RESULTS: The presence of an inlet patch was found in 0.29%
      (operator unaware) and 2.27% (operator aware) of prospectively evaluated
      patients. Inlet patches appeared as single areas in 12 patients, as twin areas in
      five, and as multiple areas in one patient. Their diameters ranged approximately
      from 3 to 25 mm. The average age of the patients (13 men) was 52.5 +/- 16.8
      years. Five patients had an active or healed peptic ulcer and only one patient
      had reflux oesophagitis. Dysphagia or throat discomfort/heartburn represented the
      symptoms leading to upper endoscopy in only one patient. Six of seven patients
      with Helicobacter pylori infection in the stomach also presented the infection in
      the heterotopic gastric mucosa. CONCLUSION: Heterotopic gastric mucosa in the
      upper oesophagus is not a rare condition. The frequency with which this condition
      is found during routine endoscopic examination is likely due to the reduced
      awareness of the examiner. The presence of inlet patches is scarcely correlated
      with specific symptoms and the patches are often infected by H. pylori, in
      patients with H. pylori positive gastritis.

PMID- 10929901
TI  - Atkinson tubes are a good cost-effective means of palliating inoperable
      oesophageal malignant strictures: an eight-year experience.
AB  - OBJECTIVE: To determine how many oesophageal and oesophago-gastric malignancies
      could be successfully intubated endoscopically with an Atkinson tube, and how
      often a metal mesh tube would be required instead. DESIGN: A consecutive series
      of 125 patients underwent endoscopy and intubation. METHODS: A total of 142
      Atkinson tubes were inserted into 122 patients, and four metal mesh stents were
      put into three patients. The median hospital stay was 3 days, and 28 patients
      were treated as day cases. RESULTS: Atkinson tube insertion failed in only one
      patient. There were eight oesophageal perforations (5.6%); the procedure-related
      mortality was 4%. Three patients required a metal mesh stent, as dilatation
      proved difficult because of prior radiotherapy in two and prior surgery in one.
      CONCLUSION: Atkinson tubes are the stents of choice for inoperable oesophageal
      tumours because of low complication rates and cost efficiency. In 20% of
      patients, day case insertion was successful. Metal mesh stents should be reserved
      for those patients with tight post-radiotherapy or post-surgical strictures when
      dilatation is difficult.

PMID- 10929902
TI  - Dysplasia of the submucous nerve plexus in slow-transit constipation of adults.
AB  - AIM: A clinicopathological entity, intestinal neuronal dysplasia type B (IND) has
      been described in children with severe constipation. The present study was
      designed to evaluate whether IND could be identified in adult patients with
      idiopathic slow-transit constipation. METHODS: Rectal biopsies were taken from 27
      constipated patients with documented slow colonic transit and 23 controls and
      stained for S100 protein, acetylcholine esterase and lactate dehydrogenase. The
      mean and maximal number of ganglion cells per ganglion, mean number of ganglia
      and mean number of ganglion cells per mm2 of submucosal tissue, mean and maximal
      diameter of ganglion cells, maximal thickness of submucosal nerve fibres, and
      number of S100-positive cells per mm2 mucosal tissue were quantified. The density
      of submucosal ganglia, presence of heterotopic ganglion cells, intensity of
      staining of the adventitial layer of submucosal arteries, and density of nerve
      fibres in submucosa and lamina propria were evaluated qualitatively. In addition,
      subjective evaluation by an experienced pathologist was performed. RESULTS: There
      were no major differences between patients and controls, except that patients had
      slightly thicker submucosal nerves than controls (30.8 +/- 1.6 versus 25.5 +/-
      2.0 microm, P < 0.05) and more frequent heterotopic ganglion cells (32 versus 6%,
      P < 0.05). Neither discriminant analysis of the morphometric data nor subjective
      evaluation was able to correctly classify the slides as originating from patients
      or controls. CONCLUSIONS: The existence of the clinicopathological entity IND in
      adults with slow-transit constipation is unlikely. For further classification of
      slow-transit constipation, rectal biopsies do not appear to be useful at present.

PMID- 10929903
TI  - Increased presence of cells containing transforming growth factor alpha (TGF
      alpha) in ulcerative colitis, both during active inflammation and in remission.
AB  - OBJECTIVE: Patients with extensive and long-standing ulcerative colitis have an
      increased risk of developing colorectal cancer and sub-epithelial fibrosis. The
      polypeptide transforming growth factor alpha (TGF-alpha) has mitogenic effects
      and it is believed that local overproduction may result in tumour formation and
      fibrosis. DESIGN: In the present study, we correlated the presence of TGF-alpha
      in ulcerative colitis with the degree of inflammation and with dysplasia.
      METHODS: Sixty two patients were investigated, 46 with ulcerative colitis (16
      with active inflammation and 20 in remission, 10 with dysplasia of the colon),
      and 16 controls with normal colonoscopy and without a history of colitis. There
      were no overlaps between the subgroups. Tissue sections from colonic biopsies
      were examined and TGF-alpha was detected by immunohistochemistry. TGF-alpha
      containing cells were characterized by double-staining with antibodies to
      eosinophil cationic protein (ECP). An antibody (EG2) recognizing eosinophils with
      an activated phenotype was also used. RESULTS: The median number of TGF-alpha
      containing cells in the mucosa was 24 per mm2 (inter-quartile range 10-51) in
      controls, 186 per mm2 (73-245) in ulcerative colitis with active inflammation, 76
      per mm2 (52-198) in remission, and 130 per mm2 (66-203) in areas of dysplasia.
      Double-staining for TGF-alpha and ECP revealed that most of the TGF-alpha
      containing cells were eosinophils, and most had an activated phenotype as judged
      by staining with EG2. CONCLUSIONS: The presence of TGF-alpha-containing cells in
      colonic mucosa is increased both in active inflammation and during remission in
      ulcerative colitis. Dysplasia is not associated with any significant increase in
      TGF-alpha-containing cells. The majority of TGF-alpha-containing cells are
      eosinophils with an activated phenotype. TGF-alpha released from these cells
      could be important for the development of complications seen in ulcerative
      colitis, such as cancer and fibrosis.

PMID- 10929904
TI  - Cerebral autoregulation in patients with end-stage liver disease.
AB  - OBJECTIVE: The aim of the present study was to determine whether cerebral
      autoregulation is absent in patients with end-stage liver disease. DESIGN: A
      prospective physiological study. METHODS: Thirty patients, 15 female (median age
      50 years, range 33-74), with biopsy-proven cirrhosis (4 Child-Pugh class B, 26
      Child-Pugh class C), had their cerebral perfusion evaluated using mean flow
      velocity (Vmean) in the middle cerebral artery as measured by transcranial
      Doppler sonography. Mean arterial pressure (MAP) was raised by intravenous
      noradrenaline (5-30 microg/min). Nine patients had no clinical signs of hepatic
      encephalopathy (HE), three were in HE stage 1, four in HE stage 2, four in HE
      stage 3 and ten in HE stage 4, respectively. RESULTS: Cerebral autoregulation was
      impaired in 13 patients, as Vmean increased from 47 (26-88) to 60 (36-109) cm/s
      during a rise in MAP from 61 (47-99) to 82 (65-121) mmHg. Vmean remained
      unchanged (preserved cerebral autoregulation) at 56 (30-119) cm/s in 17 patients
      when MAP was raised from 74 (59-90) to 95 (81-129) mmHg. Cerebral autoregulation
      was lost in 8/10 patients with HE stage 4 and only in 2/9 patients without HE (P
      = 0.023). The duration of HE stage 1-4 before the autoregulation study was
      identical for patients with preserved cerebral autoregulation compared to
      patients with impaired cerebral autoregulation, 5 (2-30) versus 6 (2-35) days,
      respectively. Baseline values of MAP were significantly lower in patients with no
      cerebral autoregulation compared to patients with preserved cerebral
      autoregulation, 61 (47-99) versus 74 (59-90) mmHg (P = 0.012). All other baseline
      values in the two groups were similar, including PaCO2, albumin, bilirubin,
      international normalization ratio, galactose elimination capacity, Child-Pugh
      class and age. CONCLUSION: Cerebral autoregulation is preserved in most patients
      with end-stage liver disease. In patients with hepatic encephalopathy and low
      MAP, however, cerebral autoregulation is impaired.

PMID- 10929905
TI  - The potential impact of high-quality MRI of the biliary tree on ERCP workload.
AB  - BACKGROUND: Magnetic resonance cholangiography (MRC) is a non-invasive method of
      imaging the biliary tree with virtually no morbidity. Endoscopic retrograde
      cholangiopancreatography (ERCP) has a significant morbidity, mortality and failed
      imaging rate. Unlike MRC, ERCP is highly dependent on the clinical team for high
      quality results and minimal morbidity. MRC requires high-quality image
      acquisition and appropriate reconstructions, with skilled reading of the images.
      OBJECTIVES: To assess the impact on ERCP workload of using MRC as the initial
      imaging modality for the biliary tree in selected patient groups, and to assess
      procedure-related morbidity and mortality. METHODS: An analysis of 1078
      consecutive ERCP examinations performed at our institution over the six years to
      1996 has been undertaken. Complications, imaging failure rates and ERCP findings
      have been analysed in the different referral categories to assess the potential
      impact of MRC on future ERCP workload and patient outcomes. RESULTS: At our
      institution, if MRC had been used as the first imaging investigation in patients
      with abdominal pain (n = 336, with or without abnormal liver function tests but
      without clinical jaundice) and those with present or past acute pancreatitis (n =
      101), we estimate that 83 (19%) would have needed to go on to ERCP, but 354 (81%)
      would not have required further invasive investigation. In these categories, this
      would have resulted in five patients with stones missed at MRC, but 14 extra
      patients with stones would have been identified whose stones would have been
      missed at ERCP (failed examinations). There would be an overall 33% reduction in
      ERCP workload and 20 serious complications related to ERCP would have been
      avoided. Overall 7% of patients would be subjected to both investigations.
      CONCLUSIONS: In the interests of efficient use of resources, minimization of
      patient complications and accurate identification of those requiring therapeutic
      ERCP, MRC should be the preferred initial investigation in selected groups of
      patients presently being subjected to ERCP.

PMID- 10929906
TI  - Quantitative hepatobiliary scintigraphy and endoscopic sphincter of Oddi
      manometry in patients with suspected sphincter of Oddi dysfunction: assessment of
      flow-pressure relationship in the biliary tract.
AB  - OBJECTIVE: In the present study, the diagnostic efficacy of quantitative
      hepatobiliary scintigraphy (QHBS) was compared with that of endoscopic sphincter
      of Oddi (SO) manometry (ESOM) in patients with a suspected SO dysfunction (SOD)
      of biliary type II or III. METHODS: Twenty cholecystectomized patients with SOD
      biliary types II and III were investigated by QHBS and by ESOM. Twenty
      asymptomatic cholecystectomized patients served as controls for scintigraphy.
      ESOM was performed by applying the station pull-through method. Then SO basal
      pressure and phasic contraction characteristics were determined. During QHBS,
      time-activity curves were generated, and the time-to-peak (Tmax), the half-time
      of excretion (T(1/2)), the duodenal appearance time (DAT) and the hilum-to
      duodenum transit time (HDTT) were then calculated. At the 60th minute of QHBS, 5
      ng/kg body weight/min caerulein was administered. RESULTS: In patients with SOD
      and elevated SO basal pressure (> 40 mmHg), QHBS parameters, such as Tmax and
      T(1/2) calculated from regions of interest over the hepatic hilum and common bile
      duct, HDTT and DAT proved to be significantly increased compared to controls:
      28.7 +/- 4.3 versus 21.1 +/- 4.6 min, 39.7 +/- 15.4 versus 18.8 +/- 2.6 min, 9.0
      +/- 3.6 versus 2.3 +/- 1.3 min and 27.1 +/- 4.9 versus 16.6 +/- 3.0 min,
      respectively. In contrast, in patients with SOD and normal SO basal pressure,
      QHBS parameters did not differ significantly from the controls. For the pooled
      data on the symptomatic patients with SOD, a statistically significant linear
      correlation was found between the SO basal pressure and the QHBS parameters.
      Although HDTT was the most sensitive scintigraphic parameter (89%), the combined
      sensitivity and specificity of Tmax and T(1/2) of the common bile duct reached
      100%. No scintigraphic sign of a paradoxical response to cholecystokinin was
      detected. CONCLUSIONS: QHBS is a useful non-invasive diagnostic method for the
      selection of SOD patients with an elevated SO basal pressure. A significant
      correlation has been established between the trans-papillary bile flow measured
      by QHBS and the SO basal pressure determined by ESOM.

PMID- 10929907
TI  - Postprandial refilling and turnover: specific gallbladder motor function defects
      in patients with gallstone recurrence.
AB  - BACKGROUND AND AIMS: Impaired gallbladder motor functions are important in the
      pathogenesis of primary cholesterol gallstones, and possibly in the pathogenesis
      of recurrent gallstones. By using ultrasonography and cholescintigraphy
      simultaneously, we recently defined new parameters of gallbladder motor function
      (postprandial refilling and turnover in addition to emptying), which were
      markedly impaired in gallstone patients. The aim of this study was to assess the
      value of these new parameters in distinguishing patients with from those without
      gallstone recurrence. METHODS: We studied 11 patients with gallstone recurrence,
      11 without gallstone recurrence (at least 40 months after complete dissolution by
      oral bile acids) and 11 healthy controls. Simultaneous measurements of
      gallbladder volume (ultrasound) and gallbladder counts (gamma-camera
      scintigraphy) were carried out in the fasting state and at 10 min intervals
      following meal ingestion, for a period of 90 min. Gallbladder refilling, turnover
      of bile and turnover index were calculated, as well as gallbladder emptying by
      both cholescintigraphy and ultrasound. RESULTS: Patients with gallstone
      recurrence had reductions in gallbladder emptying, postprandial refilling and
      gallbladder bile turnover. They also had a significant reduction in the turnover
      index (1.7 +/- 1.4) compared to controls (3.5 +/- 0.3, P < 0.01) and to patients
      without gallstone recurrence (3.1 +/- 1.5, P < 0.05). Patients without gallstone
      recurrence had only a small reduction in emptying and no reduction in
      postprandial refilling or turnover compared to controls. CONCLUSIONS: We conclude
      that impairment of gallbladder emptying persists in all patients after gallstone
      dissolution, albeit to a more pronounced extent in patients with recurrence; but
      that impairment of postprandial refilling and turnover are specific defects in
      patients with recurrence.

PMID- 10929908
TI  - Molecular alterations in gastric cancer: the role of Helicobacter pylori.
AB  - Helicobacter pylori has been classified as a human carcinogen contributing to the
      pathogenesis of gastric cancer. Extensive sero-epidemiological studies and
      recently animal experiments have established a close link between H. pylori
      infection and the development of gastric cancer. However, the molecular changes
      induced by H. pylori directly or the concomitant chronic inflammation of the
      gastric mucosa, and the impact of these changes on the subsequent development of
      gastric cancer, remain largely unknown. This review will highlight the present
      knowledge on the molecular pathogenesis of gastric cancer with an emphasis on
      molecular and genetic alterations which develop due to chronic infection of the
      gastric mucosa by H. pylori.

PMID- 10929909
TI  - The benefit/risk profile of rabeprazole, a new proton-pump inhibitor.
AB  - Acid-related diseases such as gastro-oesophageal reflux disease (GORD) and peptic
      ulcer are a common cause of morbidity and if inadequately treated can lead to
      serious complications. The proton-pump inhibitor rabeprazole has been extensively
      evaluated in well-controlled trials in North America and Europe for the acute
      treatment of erosive or ulcerative GORD and gastric and duodenal ulcers and for
      the long-term maintenance of GORD healing. The results show that rabeprazole has
      a favourable benefit/risk profile for each indication. Rabeprazole 10 and 20 mg
      given once daily in the morning was highly effective in producing and maintaining
      healing, providing symptom relief, and improving overall well-being. Healing
      rates for rabeprazole were equivalent to omeprazole in all indications, and
      superior (GORD healing and duodenal ulcer healing) or equivalent (gastric ulcer
      healing) to the histamine 2-receptor antagonist ranitidine. Symptom relief
      provided by rabeprazole was equivalent or superior to comparator drugs.
      Rabeprazole was well tolerated in both short- and long-term studies. The
      incidence of treatment-emergent signs and symptoms related to rabeprazole was
      low, and these were generally mild or moderate in severity. The overall rate of
      discontinuations due to adverse events was approximately 3%. There were no deaths
      related to rabeprazole therapy. These findings indicate a favourable benefit/risk
      profile for each intended use.

PMID- 10929910
TI  - Perforation--a rare complication of a small-bowel carcinoid.
AB  - Carcinoids are rare compared to other tumours of the gastrointestinal tract, but
      present a significant portion of tumours of the small intestine. The case of a 50
      year-old man who suffered perforation of a small-bowel carcinoid after failed
      diagnostic trials is reported here. Since intestinal perforation is rarely the
      first sign of the presence of a carcinoid, it is useful to bear this in mind when
      dealing with unclear pathological changes of the small intestine.

PMID- 10929911
TI  - Churg-Strauss syndrome and granulomatous cholangiopathy.
AB  - Churg-Strauss syndrome is a vasculitis that is known to have gastroenterological
      manifestations. There have been no reports associating it with liver disease. We
      present a case of this syndrome in a man who was found to develop a co-existent
      cholangiopathy. It is likely that this represents an associated granulomatous
      reaction consequent to a hepatic manifestation of the vasculitis.

PMID- 10929912
TI  - Intra-hepatic haematoma complicating transjugular intra-hepatic portosystemic
      shunt for Budd-Chiari syndrome associated with anti-phospholipid antibodies,
      aplastic anaemia and chronic hepatitis C.
AB  - Portal venous decompression with transjugular intra-hepatic portosystemic shunt
      (TIPS) is a new approach in the treatment of Budd-Chiari syndrome. We report on a
      31-year-old female with Budd-Chiari syndrome due to anti-phospholipid antibodies
      with compression of the inferior vena cava treated with TIPS and stenting of the
      inferior vena cava. TIPS was complicated by massive intra-hepatic haematoma which
      was managed conservatively. Treatment options and pathogenic mechanisms of Budd
      Chiari syndrome under the rare coincidence of aplastic anaemia and anti
      phospholipid syndrome are discussed. TIPS may be considered for venous
      decompression in Budd-Chiari syndrome, but physicians should be aware of
      potential TIPS' complications in these patients.

PMID- 10929913
TI  - Successful treatment of hepatic hydrothorax with octreotide.
AB  - Hepatic hydrothorax is a rare complication of cirrhosis. Controlling ascites
      formation is the goal of therapy. We report the case of an adult patient
      presenting with alcoholic cirrhosis who developed first a symptomatic
      hydrothorax, refractory to diuretics and fluid and sodium restriction, and then
      an hepatorenal syndrome. Treatment consisted of chest tube insertion and 5 days'
      intravenous infusion of octreotide. Complete clinical and biological data were
      reviewed. Octreotide administration resulted in an increased urinary outflow and
      sodium output, concomitant with improved renal function. The patient has been
      free of symptoms after discharge from hospital for a follow-up period of 5
      months. This observation raises interesting issues regarding the possible utility
      of splanchnic vasoconstrictors, reducing portal hypertension, in the treatment of
      refractory hepatic hydrothorax.

PMID- 10929914
TI  - Factor V Leiden is not more frequent in inflammatory bowel disease.

PMID- 10929915
TI  - Pharmacologic strategies for treating gastroesophageal reflux disease.
AB  - OBJECTIVE: This paper presents a synopsis of the pathophysiology of
      gastroesophageal reflux disease (GERD) and the efficacy, safety, and cost of the
      agents commonly used in its treatment. BACKGROUND: Symptomatic relief of GERD can
      be obtained with lifestyle changes (avoidance of factors that may exacerbate
      symptoms, such as overeating and use of alcohol and tobacco) and use of over-the
      counter medications such as antacids or histamine-2 (H2)-receptor antagonists.
      When these measures are unsuccessful, treatment with prescription-strength
      medications is required to prevent complications, such as Barrett's esophagus or
      esophageal adenocarcinoma. METHODS: Current guidelines for the management of GERD
      were identified through a MEDLINE search of the English-language literature from
      January 1995 through December 1999 and a search of the bibliographies of
      identified articles. CONCLUSION: Patients who do not respond to initial therapy
      should be managed with prescription-strength H2-receptor antagonists. Endoscopy
      should be considered for patients with atypical or refractory symptoms. Patients
      with a confirmed diagnosis of refractory GERD, severe esophagitis, Barrett's
      esophagus, or peptic stricture should be treated with and maintained on a proton
      pump inhibitor.

PMID- 10929916
TI  - Short-Course antimicrobial therapy for upper respiratory tract infections.
AB  - OBJECTIVE: This review examines the issues surrounding short-course antimicrobial
      therapy of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis,
      acute (suppurative) otitis media, and acute sinusitis. BACKGROUND: Accumulating
      evidence suggests that short-course (ie, < or = 5 days) antimicrobial therapy may
      have equivalent or superior efficacy compared with traditional longer (10- to 14
      day) therapies. RESULTS: In GABHS tonsillopharyngitis, short-course therapy with
      6 days of amoxicillin, 4 or 5 days of various cephalosporins, and 5 days of
      azithromycin (10 mg/kg once daily on all 5 days in pediatric patients) are all
      reasonable alternatives to traditional 10-day penicillin therapy. In
      uncomplicated acute (suppurative) otitis media, single-dose intramuscular
      ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be
      effective in > or = 80% of patients. However, more research is needed in children
      aged <2 years, since short-course therapy may not be successful in most patients
      in this population. In sinusitis, most short-course therapy data have involved
      acute maxillary disease in adult patients. Preliminary results are encouraging,
      but more study is needed, especially in children. CONCLUSIONS: Cost-containment
      in antimicrobial therapy should include consideration of short-course therapy in
      the management of upper respiratory tract infections.

PMID- 10929917
TI  - Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced
      mitochondrial toxicity.
AB  - OBJECTIVE: This paper reviews the function of the mitochondria and the mechanisms
      by which nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) cause
      mitochondrial toxicity. BACKGROUND: Highly active antiretroviral therapy (HAART)
      reduces rates of morbidity and mortality due to HIV disease. However, long-term
      treatment with these drugs may be associated with adverse effects. Nucleoside and
      nucleotide analogues are potent inhibitors of HIV reverse transcriptase and have
      become the cornerstone of HAART. Unfortunately, these drugs have also been shown
      to inhibit cellular polymerases, most notably mitochondrial DNA polymerase gamma.
      RESULTS: Studies of the NRTIs in enzyme assays and cell cultures demonstrate the
      following hierarchy of mitochondrial DNA polymerase gamma inhibition: zalcitabine
      > didanosine > stavudine > lamivudine > zidovudine > abacavir. In vitro
      investigations have also documented impairment of the mitochondrial enzymes
      adenylate kinase and the adenosine diphosphate/adenosine triphosphate
      translocator. Inhibition of DNA polymerase gamma and other mitochondrial enzymes
      can gradually lead to mitochondrial dysfunction and cellular toxicity. The
      clinical manifestations of NRTI-induced mitochondrial toxicity resemble those of
      inherited mitochondrial diseases (ie, hepatic steatosis, lactic acidosis,
      myopathy, nephrotoxicity, peripheral neuropathy, and pancreatitis). Fat
      redistribution syndrome, or HIV-associated lipodystrophy, is another side effect
      attributed in part to NRTI therapy. The morphologic and metabolic complications
      of this syndrome are similar to those of the mitochondrial disorder known as
      multiple symmetric lipomatosis: suggesting that this too may be related to
      mitochondrial toxicity. The pathophysiology of less common adverse effects of
      nucleoside analogue therapy, such as diabetes, ototoxicity, and retinal lesions,
      may be related to mitochondrial dysfunction but have not been adequately studied.
      CONCLUSION: NRTls can block both HIV reverse transcriptase and mitochondrial DNA
      polymerase gamma. Inhibition of the latter enzyme is the most likely cause of the
      adverse effects associated with these drugs.

PMID- 10929918
TI  - Combined metformin and insulin therapy for patients with type 2 diabetes
      mellitus.
AB  - OBJECTIVE: This study was undertaken to assess the effects of combined treatment
      with insulin and metformin in patients with type 2 diabetes mellitus in whom
      dietary measures, weight control, and oral antihyperglycemic therapy had failed.
      BACKGROUND: Insulin resistance in peripheral tissues, increased hepatic
      gluconeogenesis, and impaired insulin secretion are the underlying factors in the
      development of type 2 diabetes. Metformin is a biguanide antihyperglycemic agent
      that increases peripheral insulin sensitivity, reduces hepatic gluconeogenesis,
      and decreases intestinal glucose absorption. METHODS: Thirty-one patients (24
      women, 7 men; mean age, 61.8 years; mean body mass index [BMI], 28.0 kg/m2) were
      enrolled in this randomized, double-blind, 2-way, crossover, placebo-controlled
      study. Patients with type 2 diabetes who were treated previously with insulin or
      oral hypoglycemic agents and who had a glycosylated hemoglobin (HbA1c) level >9%
      or a fasting blood glucose level >8 mmol/L were included. Patients who were being
      treated with oral agents were switched to insulin therapy and required to
      maintain stable blood glucose control for 2 months prior to randomization.
      Patients received insulin plus either metformin 1,700 mg/d or placebo for 5
      months, followed by a 2-month washout period, and were then crossed over to the
      other treatment arm for 5 months of additional treatment (total treatment period:
      12 months). RESULTS: Thirty patients completed the study; 1 patient withdrew
      early because of hypoglycemia. Compared with placebo, metformin produced
      significant reductions from overall baseline in mean daily insulin dose
      requirement (-8.69 units (17.2%], P < 0.001), HbA1c level (-0.74 [9.9%], P =
      0.005), serum fructosamine level (-44.40 micromol/L, P = 0.026), 24-hour blood
      glucose profile (P = 0.008), and total cholesterol level (-0.42 mmol/L, P =
      0.005). No treatment effects were observed on body weight, blood pressure, serum
      high-density lipoprotein cholesterol levels, or serum triglyceride levels. There
      was no correlation between BMI and reduction in HbA1C. No major side effects were
      reported. CONCLUSIONS: Combination therapy with metformin and insulin improves
      glycemic control and reduces insulin requirements. with no major side effects, in
      patients with type 2 diabetes and may improve the risk profile in this patient
      population.

PMID- 10929919
TI  - A randomized, double-masked, clinical study of the efficacy of four nonsteroidal
      anti-inflammatory drugs in pain control after excimer laser photorefractive
      keratectomy.
AB  - OBJECTIVE: This study assessed the efficacy of 4 nonsteroidal anti-inflammatory
      drugs (NSAIDs) after excimer laser photorefractive keratectomy (PRK). BACKGROUND:
      Inadequate control of pain after PRK surgery can be a severe source of distress
      to patients and can interfere with their willingness to undergo a second PRK
      procedure. METHODS: This randomized, double-masked, placebo-controlled clinical
      study was conducted in 125 patients. Four NSAIDs (diclofenac, flurbiprofen,
      ketorolac, and indomethacin) were tested against a placebo group (artificial
      tears). Pain levels after PRK were quantified using Present Pain Intensity (PPI)
      and Pain Rating Indices based on rank values (PRI[R]) scores, both of which were
      calculated using patient responses to a modified McGill Pain Questionnaire. The
      PRI(R) consisted of 4 subscales-sensory (S), affective (A), evaluative (E), and
      miscellaneous (M)-as well as a total score (T). RESULTS: Three hours after PRK,
      no differences in PPI scores were found between the ketorolac, diclofenac, and
      indomethacin groups, whereas placebo was significantly less effective than the
      NSAIDs. Patients who received flurbiprofen reported PPI scores that were
      significantly lower (P < 0.001) than those of patients who received diclofenac
      and indomethacin, but PPI scores in the flurbiprofen and the ketorolac groups did
      not differ significantly. Twenty-four hours after surgery, patients treated with
      flurbiprofen, ketorolac, and diclofenac reported the lowest PPI scores compared
      with those treated with indomethacin and placebo (P < 0.001). Moreover,
      flurbiprofen-treated patients also had the lowest PRI(R)T scores (P < 0.001).
      When the pain rating index was examined by subclass, a significantly lower
      PRI(R)S score was detected in the flurbiprofen group at 24 hours (P < 0.001). The
      PRI(R)A score was significantly higher in the placebo and indomethacin groups
      compared with the other groups (P < 0.001). At the 48- and 72-hour time points,
      flurbiprofen-treated patients again reported significantly lower PPI and PRI(R)T
      scores (P < 0.001 for both) in pair-wise comparisons with the other treatment
      groups. The number of patients who self-administered additional oral analgesics
      did not differ significantly between the groups. However, the mean number of
      analgesic tablets used was significantly higher in the placebo group than in any
      NSAID group (P < 0.001). The ketorolac group had the largest number of patients
      complaining of itching (P < 0.043). No other subjective symptoms were
      significantly different across groups. Finally, all NSAIDs, except flurbiprofen,
      prolonged the mean reepithelialization period slightly (P < 0.001). CONCLUSIONS:
      Flurbiprofen appeared to be the most effective NSAID for the treatment of pain,
      even at 24 hours after surgery when pain was at a maximum.

PMID- 10929921
TI  - Primary prevention of acute respiratory tract infections in children using a
      bacterial immunostimulant: a double-masked, placebo-controlled clinical trial.
AB  - BACKGROUND: Acute respiratory tract infections (ARTIs) are among the main causes
      of morbidity and mortality in children. The bacterial extract OM-85 BV has shown
      some protective effect for ARTIs in preschool children and a reduction in
      exacerbations of chronic bronchitis in adults. OBJECTIVES: This trial reports
      results of a double-masked, placebo-controlled, parallel-group clinical study
      that assessed the efficacy and tolerability of OM-85 BV in the prevention of
      ARTIs in school girls living in an orphanage. METHODS: Two hundred girls (age
      range, 6 to 13 years) living in an orphanage entered the trial. Participants were
      randomly allocated to receive either OM-85 BV or placebo for 10 consecutive days
      a month for 3 consecutive months. Patients were followed up for 6 months,
      including the administration period. The trial began in September 1996 and
      finished in March 1997. Primary end points were the type and number of
      infections. Secondary end points included when an infection occurred, time to
      clinical cure, severity of infection, absenteeism from school due to an ARTI,
      number of antibiotics or other drugs prescribed, and duration of concomitant drug
      treatment. RESULTS: During the trial, patients in the OM-85 BV group experienced
      143 ARTIs (135 upper ARTIs and 8 otitis episodes) and patients in the placebo
      group experienced 299 ARTIs (273 upper ARTIs, 1 lower ARTI, and 25 otitis
      episodes). The median number of ARTIs was 1.0 (0.0, 3.0; 5th percentile, 95th
      percentile) in the OM-85 BV group compared with 3.0 (2.0, 4.0; 5th percentile,
      95th percentile) in the placebo group. This difference was statistically
      significant (P < 0.001). Participants who received OM-85 BV also showed
      significantly better results (P < 0.001) than participants who received placebo
      in terms of median duration of illness, median number of missed school days due
      to an ARTI, median number of antibiotic and drug courses, and median duration of
      concomitant treatment. There were significant differences (P < 0.05) in severity
      of ARTIs during month 4 of the trial, with patients receiving OM-85 BV showing
      less severe ARTIs than patients receiving placebo and shorter mean time to
      clinical cure from the second month to the fourth month. No adverse events
      related to the trial medications were reported. CONCLUSIONS: OM-85 BV had a
      preventive effect on ARTIs in the school girls, with a reduction in the
      antibiotic requirements and the duration of ARTIs. Future studies are needed to
      further explore the role of OM-85 BV in the prevention of ARTIs.

PMID- 10929920
TI  - Effectiveness and tolerability of zafirlukast for the treatment of asthma in
      children.
AB  - OBJECTIVE: This study was undertaken to examine the dose-response relationship of
      zafirlukast (5 to 40 mg BID) and to assess the efficacy and tolerability of the
      10-mg BID dose in school-aged children with mild to moderate asthma. BACKGROUND:
      The efficacy and tolerability of zafirlukast, an oral leukotriene-receptor
      antagonist, has been demonstrated in adolescents and adults aged > or = 12 years.
      METHODS: Data from 2 placebo-controlled, parallel-group, multicenter trials
      (trial 1, 4-week double-blind; trial 2, 6-week double-blind) were integrated.
      Children aged 5 to 11 years were randomly assigned to receive zafirlukast 5 mg
      BID (n = 99), 10 mg BID (n = 205), 20 mg BID (n = 105), 40 mg BID (n = 99), or
      placebo (n = 206). The primary outcome was change from baseline in forced
      expiratory volume in 1 second (FEV1) expressed as percent of predicted normal.
      Secondary outcomes were FEV1 (L), morning and evening peak expiratory flow, peak
      flow variability, short-acting beta2-agonist use, asthma episode score, and
      nights awakened by asthma. RESULTS: Mean baseline FEV1 was 76.5% of predicted.
      The greatest improvements were generally seen with zafirlukast 5 mg BID or 10 mg
      BID, with no additional clinically significant benefits seen at higher doses. The
      pooled data analysis showed that 10 mg BID compared with placebo significantly
      improved (P < 0.045) all efficacy outcomes except asthma-episode score and nights
      awakened with asthma. However, in the subset of children who had > or = 1 night
      awakened per week at baseline (zafirlukast 10 mg BID = 78; placebo = 86), 10 mg
      BID significantly reduced nights awakened (P = 0.009) (mean difference from
      placebo at end point = -0.81 night/wk). All zafirlukast doses were well tolerated
      and had tolerability profiles that were clinically indistinguishable from
      placebo. CONCLUSION: These results support the effectiveness and tolerability of
      the 10-mg BID dose of zafirlukast for the prophylaxis and chronic treatment of
      mild to moderate asthma in children.

PMID- 10929922
TI  - Efficacy and tolerability of loratadine versus fexofenadine in the treatment of
      seasonal allergic rhinitis: a double-blind comparison with crossover treatment of
      nonresponders.
AB  - BACKGROUND: Nonsedating antihistamines are well-established treatment for
      seasonal allergic rhinitis (SAR), but patients do not always respond to the first
      antihistamine prescribed. OBJECTIVE: This double-blind, double-dummy, randomized,
      2-phase, multicenter study was designed primarily to compare the therapeutic
      responses to loratadine and fexofenadine in patients who failed initial therapy
      with the other drug. METHODS: Male and female patients aged 12 to 60 years
      received loratadine 10 mg once daily (n = 331) or fexofenadine 60 mg twice daily
      (n = 328) for 14 days (phase 1); nonresponders (ie, those who had <25% reduction
      in the sum of 5 SAR symptoms rated by the investigator on a 4-point scale)
      subsequently received the alternate medication for 14 days (phase 2). The
      investigator's rating of relief (complete, marked, moderate, or slight relief of
      symptoms or treatment failure) at the end of phase 2 was the primary efficacy
      measure; changes in total symptom severity (TSS) assessed by the investigator (4
      point scale) and the patient (11-point visual analog scale) were secondary
      measures. RESULTS: Mean decreases in TSS were significantly greater with
      loratadine than with fexofenadine for the 659 patients who completed phase 1 (
      12.7 vs -10.2, respectively; P = 0.019; patient assessment) and for the 389
      patients who responded to initial therapy (-6.6 vs -6.1, respectively; P = 0.037;
      investigator assessment). Of the 389 patients who responded to initial therapy,
      61.0% had received loratadine and 57.0% had received fexofenadine. More
      nonresponders to initial therapy had moderate, marked, or complete relief of
      symptoms after switching to loratadine than after switching to fexofenadine
      (62.4% vs 51.2%, respectively; P = 0.005) and treatment failure in 10.6% vs
      21.7%, respectively (P = 0.011). CONCLUSION: Overall, ioratadine provided
      significantly better therapeutic response than fexofenadine in patients who
      failed to respond to initial therapy with the other drug.

PMID- 10929923
TI  - Quality-of-Life drugs?

PMID- 10929924
TI  - Medical services utilization and charge comparisons between elderly patients with
      and without Alzheimer's disease in a managed care organization.
AB  - OBJECTIVES: The purposes of this study were to describe the health service
      utilization patterns and the associated charges for elderly patients (aged > or =
      65 years) diagnosed with Alzheimer's disease (AD) enrolled in a managed care
      organization (MCO), and to compare these patterns and charges with those of
      elderly enrollees not diagnosed with AD (non-AD). METHODS: We analyzed medical
      claims data over a 12-month period for the population of elderly patients with a
      diagnosis of AD or AD-related dementia, and for all other elderly patients
      enrolled in an integrated MCO. Comparisons were made at the level of service
      location (eg, inpatient hospital, outpatient hospital, physician's office).
      RESULTS: For a total of 250 patients diagnosed with AD (66.0% female, 34.0% male;
      mean age. 80.5 years), health care charges were 1.6 times higher per patient per
      year than the corresponding charges for 13,553 non-AD patients (58.6% female,
      41.4% male; mean age, 73.3 years). AD patients received 1.7 times more health
      care services per patient per year than their non-AD counterparts. CONCLUSIONS:
      Despite the lack of nursing home and prescription drug data, our results show
      that AD patients in this MCO used more health care services and had higher annual
      medical care charges than non-AD patients. If MCOs conduct similar analyses of
      elderly AD patients' patterns of care and compare these with the patterns of
      elderly non-AD patients, they may be able to pinpoint areas of disparity in
      medical care and improve service delivery for AD patients.

PMID- 10929925
TI  - The role of elastoviscosity in the efficacy of viscosupplementation for
      osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular
      weight hyaluronan.

PMID- 10929926
TI  - Promising new approaches to the management of obesity.
AB  - The pathophysiology of obesity is complex with many different pathways involved.
      A better understanding of these weight-regulating mechanisms has lead to the
      identification of new targets for anti-obesity agents. Most attention has been
      given to the centrally acting neuropeptides regulating food intake. Leptin,
      playing a key-role, exerts its action through several neuropeptides such as
      neuropeptide Y, alpha-melanocyte stimulating hormone and agouti related protein.
      Cocaine- and amphetamine-regulated transcript peptide and the orexins are the
      latest discovered peptides acting at the level of the hypothalamus. Targets for
      new drugs acting on peptides secreted from the periphery are cholecystokinin and
      glucagon-like peptide 1. Another potential target in the treatment of obesity is
      increasing energy expenditure via beta3 adrenoceptors or uncoupling proteins.
      These new pharmacological agents in development could be valuable adjuncts to
      more traditional treatment strategies such as dietary treatment,
      behavioural/psychological counselling and physical activity.

PMID- 10929927
TI  - Is there a growing role for endocrine therapy in the treatment of breast cancer?
AB  - Novel biochemical findings on the molecular mechanisms of estrogen actions may
      help us to understand some of the unexplained observations seen in breast cancer
      treatment and suggest new therapeutic opportunities. Thus, apart from the
      challenge of improving the clinical treatment of patients with advanced disease,
      results from trials in this setting may reveal new therapeutic principles that
      may be evaluated in the adjuvant setting. The role of endocrine therapy in
      metastatic as well as early breast cancer is increasing, and the possibility of
      improving cure rates for breast cancer by implementing therapy with novel
      aromatase inhibitors in the adjuvant setting is exciting. While the results from
      prevention trials are most interesting, suggesting the possibility of reducing
      breast cancer incidence in high-risk groups, more data are needed before we can
      decide whether such interventions are warranted in women at high risk of
      developing breast cancer.

PMID- 10929928
TI  - Newer anticonvulsants: comparative review of drug interactions and adverse
      effects.
AB  - The tolerability and drug interaction profiles of 6 new anticonvulsants:
      oxcarbazepine, vigabatrin, lamotrigine, gabapentin, tiagabine and topiramate, are
      reviewed. In general, these new anticonvulsants are well tolerated and drug
      interaction problems are minor with the exception of the risk of failure of oral
      contraceptives during treatment with oxcarbazepine or topiramate. In this review,
      the clinical implications of the tolerability of these drugs are discussed for
      different patient groups. The choice of which new anticonvulsant for which
      patient depends upon individual factors, in particular, seizure type,
      tolerability and practical administration factors. Treating elderly patients may
      be complicated by an increased sensitivity to adverse effects as these patients
      very often receive polytherapy for accompanying diseases. Drugs with very simple
      pharmacokinetic properties may be preferred in this group. Women of childbearing
      age face specific problems related to the epilepsy and to treatment with
      anticonvulsants. These include impaired fertility, failure of oral contraceptives
      and the risk of birth defects. Some new anticonvulsants may be suggested in
      preference to classical drugs to avoid these problems, but the human experience
      with newer anticonvulsants is still limited and, therefore, so is knowledge of
      the risk of congenital malformations in the offspring of mothers taking
      anticonvulsants. Psychiatric and behavioural changes frequently complicate
      treatment of patients with mental retardation. Some of the new anticonvulsants,
      in particular those affecting the gamma-aminobutyric acid (GABA) system such as
      vigabatrin, seem to exacerbate this problem and should be used with caution in
      these patients.

PMID- 10929929
TI  - Humoral immune response to influenza vaccination in patients from high risk
      groups.
AB  - Influenza is one of the most common respiratory diseases. Infections caused by
      this virus may be very serious and can lead to severe complications. So far, the
      most effective method of protection against influenza is annual vaccination. The
      Advisory Committee on Immunisation Practices recommends vaccination against
      influenza for some groups of people. Unfortunately, in spite of these clear
      indications, a large number of patients are not vaccinated. This article reviews
      the current scientific literature on immunological response to influenza
      vaccination in patients who are at especially high risk for serious post
      influenza complications and for whom immunisation against this virus is strongly
      recommended. Results of studies carried out in Poland and other countries in
      elderly people, in patients with pulmonary diseases, renal diseases, diabetes
      mellitus, cancer and haemophilia, and in those with HIV infection are presented.
      In this review, we focus on the immune response to haemagglutinin. There are some
      discrepancies between the results of studies carried out by different authors in
      high risk groups of patients. Some investigations indicated poorer humoral
      response to influenza vaccine in these groups, while others showed responses
      comparable to those in healthy individuals. These differences may be explained by
      differences in types and stages of the chronic diseases, in the treatment and
      composition of influenza vaccines, and also patients' ages, vaccination history
      and prevaccination antibody titres. Influenza vaccines are well tolerated in high
      risk patients, and all adverse reactions are generally mild and similar to those
      observed in healthy people. Although, in some cases, immunological responses to
      influenza vaccination measured in the whole study group were poor, there were
      some individual patients who, after vaccination, developed antihaemaglutinin
      antibody titres which are considered to give protection against the infection or
      contribute to a milder course of the disease.

PMID- 10929932
TI  - Ropinirole: a review of its use in the management of Parkinson's disease.
AB  - Ropinirole, a non-ergoline dopamine agonist, has selective affinity for dopamine
      D2-like receptors and little or no affinity for non-dopaminergic brain receptors.
      Ropinirole is indicated as adjunct therapy to levodopa in patients with advanced
      Parkinson's disease. It is also indicated, and recent clinical trials have
      focused on its use, as monotherapy in patients with early Parkinson's disease. In
      the symptomatic treatment of early Parkinson's disease ropinirole monotherapy was
      significantly more effective than placebo in 2 multicentre, randomised, double
      blind trials of 3 to 12 months duration as assessed by the Unified Parkinson's
      Disease Rating Scale (UPDRS) motor scores and Clinical Global Impression/Clinical
      Global Evaluation Scales. In a similarly designed 3-year comparative study with
      bromocriptine, ropinirole recipients showed a significant improvement in UPDRS-
      activities of daily living (ADL) scores; however, motor scores were similar
      between the 2 groups. Ropinirole and levodopa treatments were similar in efficacy
      as measured by UPDRS ADL scores, although ropinirole recipients showed
      significantly less improvement on UPDRS motor scores at the 5-year study end
      point in a multicentre, randomised double-blind trial. As an adjunct therapy to
      levodopa in patients with more advanced Parkinson's disease, ropinirole was
      reported to be as effective as bromocriptine and significantly more effective
      than placebo. In general in the comparisons with placebo ropinirole allowed a >
      or =20% reduction in the concomitant dose of levodopa without compromising
      efficacy in a significant proportion of patients and, in some trials decreased
      the amount of awake time spent in the 'off' state ('off' state is defined as a
      gradual return to parkinsonism despite adequate medication). Ropinirole was well
      tolerated either as monotherapy or as an adjunct to levodopa treatment. Nausea,
      dizziness and somnolence were the most commonly reported adverse events and were
      reported at a higher incidence by patients receiving ropinirole than by those
      receiving placebo. In patients with early Parkinson's disease, ropinirole
      generally showed a similar overall tolerability profile to bromocriptine
      although, over a 3-year period nausea was more commonly reported with ropinirole
      recipients. In a 5-year study, the incidence of dyskinesia was significantly
      lower with ropinirole than with levodopa regardless of levodopa supplementation.
      Prior to the addition of supplementary levodopa 5% of ropinirole recipients had
      experienced dyskinesia compared with 36% of those receiving levodopa.
      CONCLUSIONS: In patients with early Parkinson's disease, ropinirole monotherapy
      was more efficacious than bromocriptine with regard to improvement in activities
      of daily living, and need for supplemental levodopa. Ropinirole recipients had a
      higher requirement for levodopa supplementation than levodopa recipients in a 5
      year study, but the incidence of dyskinesia was significantly lower with
      ropinirole than with levodopa (markedly so in the one third of ropinirole
      recipients who were able to remain on monotherapy with no levodopa
      supplementation). Thus available data suggest that ropinirole may provide a means
      of treating early Parkinson's disease while minimising the risk of dyskinesia and
      delaying the need for supplemental levodopa in some patients. In addition,
      ropinirole is also efficacious in the management of more advanced Parkinson's
      disease in patients who are experiencing motor complications after long term
      levodopa use.

PMID- 10929931
TI  - A rational approach to drug therapy of type 2 diabetes mellitus.
AB  - Several new pharmacological agents have recently been developed to optimise the
      management of type 2 (non-insulin-dependent) diabetes mellitus. The aim of this
      article is to briefly review the various therapeutic agents available for
      management of patients with type 2 diabetes mellitus and to suggest a potential
      approach to drug selection. There are three general therapeutic modalities
      relevant to diabetes care. The first modality is lifestyle adjustments aimed at
      improving endogenous insulin sensitivity or insulin effect. This can be achieved
      by increased physical activity and bodyweight reduction with diet and behavioural
      modification, and the use of pharmacological agents or surgery. This first
      modality is not discussed in depth in this article. The second modality involves
      increasing insulin availability by the administration of exogenous insulin,
      insulin analogues, sulphonylureas and the new insulin secretagogue, repaglinide.
      The most frequently encountered adverse effect of these agents is hypoglycaemia.
      Bodyweight gain can also be a concern, especially in patients who are obese. The
      association between hyperinsulinaemia and premature atherosclerosis is still a
      debatable question. The third modality consists of agents such as biguanides and
      thiazolidinediones which enhance insulin sensitivity, or agents that decrease
      insulin requirements like the alpha-glucosidase inhibitors. Type 2 diabetes
      mellitus is a heterogeneous disease with multiple underlying pathophysiological
      processes. Therapy should be individualised based on the degree of
      hyperglycaemia, hyperinsulinaemia or insulin deficiency. In addition, several
      factors have to be considered when prescribing a specific therapeutic agent.
      These factors include efficacy, safety, affordability and ease of administration.

PMID- 10929933
TI  - Tramadol: a review of its use in perioperative pain.
AB  - Tramadol is a synthetic, centrally acting analgesic agent with 2 distinct,
      synergistic mechanisms of action, acting as both a weak opioid agonist and an
      inhibitor of monoamine neurotransmitter reuptake. The 2 enantiomers of racemic
      tramadol function in a complementary manner to enhance the analgesic efficacy and
      improve the tolerability profile of tramadol. In several comparative, well
      designed studies, oral and parenteral tramadol effectively relieved moderate to
      severe postoperative pain associated with surgery. Its overall analgesic efficacy
      was similar to that of morphine or alfentanil and superior to that of
      pentazocine. Tramadol provided effective analgesia in children and in adults for
      both inpatient and day surgery. Tramadol was generally well tolerated in clinical
      trials. The most common adverse events (incidence of 1.6 to 6.1%) were nausea,
      dizziness, drowsiness, sweating, vomiting and dry mouth. Importantly, unlike
      other opioids, tramadol has no clinically relevant effects on respiratory or
      cardiovascular parameters at recommended doses in adults or children. Tramadol
      also has a low potential for abuse or dependence. CONCLUSIONS: The efficacy of
      tramadol for the management of moderate to severe postoperative pain has been
      demonstrated in both inpatients and day surgery patients. Most importantly,
      unlike other opioids, tramadol has no clinically relevant effects on respiratory
      or cardiovascular parameters. Tramadol may prove particularly useful in patients
      with poor cardiopulmonary function, including the elderly, the obese and smokers,
      in patients with impaired hepatic or renal function, and in patients in whom
      nonsteroidal anti-inflammatory drugs are not recommended or need to be used with
      caution. Parenteral or oral tramadol has proved to be an effective and well
      tolerated analgesic agent in the perioperative setting.

PMID- 10929930
TI  - Current, new and future treatments in dyslipidaemia and atherosclerosis.
AB  - The new therapeutic options available to clinicians treating dyslipidaemia in the
      last decade have enabled effective treatment for many patients. The development
      of the HMG-CoA reductase inhibitors (statins) have been a major advance in that
      they possess multiple pharmacological effects (pleiotropic effects) resulting in
      potent reductions of low density lipoproteins (LDL) and prevention of the
      atherosclerotic process. More recently, the newer fibric acid derivatives have
      also reduced LDL to levels comparable to those achieved with statins, have
      reduced triglycerides, and gemfibrozil has been shown to increase high density
      lipoprotein (HDL) levels. Nicotinic acid has been made tolerable with sustained
      release formulations, and is still considered an excellent choice in elevating
      HDL cholesterol and is potentially effective in reducing lipoprotein(a) [Lp(a)]
      levels, an emerging risk factor for coronary heart disease (CHD). Furthermore,
      recent studies have reported positive lipid-lowering effects from estrogen and/or
      progestogen in postmenopausal women but there are still conflicting reports on
      the use of these agents in dyslipidaemia and in females at risk for CHD. In
      addition to lowering lipid levels, these antihyperlipidaemic agents may have
      directly or indirectly targeted thrombogenic, fibrinolytic and atherosclerotic
      processes which may have been unaccounted for in their overall success in
      clinical trials. Although LDL cholesterol is still the major target for therapy,
      it is likely that over the next several years other lipid/lipoprotein and
      nonlipid parameters will become more generally accepted targets for specific
      therapeutic interventions. Some important emerging lipid/lipoprotein parameters
      that have been associated with CHD include elevated triglyceride, oxidised LDL
      cholesterol and Lp(a) levels, and low HDL levels. The nonlipid parameters include
      elevated homocysteine and fibrinogen, and decreased endothelial-derived nitric
      oxide production. Among the new investigational agents are inhibitors of squalene
      synthetase, acylCoA: cholesterol acyltransferase, cholesteryl ester transfer
      protein, monocyte-macrophages and LDL cholesterol oxidation. Future applications
      may include thyromimetic therapy, cholesterol vaccination, somatic gene therapy,
      and recombinant proteins, in particular, apolipoproteins A-I and E. Non-LDL
      related targets such as peroxisome proliferator-activating receptors, matrix
      metalloproteinases and scavenger receptor class B type I may also have clinical
      significance in the treatment of atherosclerosis in the near future. Before lipid
      lowering therapy, dietary and lifestyle modification is and should be the first
      therapeutic intervention in the management of dyslipidaemia. Although current
      recommendations from the US and Europe are slightly different, adherence to these
      recommendations is essential to lower the risk of atherosclerotic vascular
      disease, more specifically CHD. New guidelines that are expected in the near
      future will encompass global opinions from the expert scientific community
      addressing the issue of target LDL goal (aggressive versus moderate lowering) and
      the application of therapy for newer emerging CHD risk factors.

PMID- 10929936
TI  - A null mutation in a bZIP factor confers ABA-insensitivity in Arabidopsis
      thaliana.
AB  - We have used a modification of the classical ABA-insensitive screen (Koornneef et
      al. 1984) to isolate novel mutations in the ABA signal transduction pathway of
      Arabidopsis thaliana. In our screen, mutants were recovered on the basis of their
      growth-insensitivity to ABA (GIA) rather than germination-insensitivity. Here we
      present the isolation of the gia1 mutant as well as the identification of the
      gia1 gene by positional cloning and complementation studies. GIA1 is predicted to
      code for a bZIP transcription factor with high homology to previously
      characterized plant bZIP transcription factors (DPBF1, ABFs and TRAB1) known for
      their ability to bind ABA-responsive DNA elements. Our results provide in vivo
      evidence that a bZIP factor may indeed be involved in ABA signaling. Since GIA1
      turned out to be identical to ABI5, we designated GIA1 as ABI5 in the present
      paper.

PMID- 10929934
TI  - Eprosartan: a review of its use in the management of hypertension.
AB  - Eprosartan is a potent and selective angiotensin II subtype 1 receptor
      antagonist. Results of large (n > 100) randomised double-blind studies in
      patients with mild, moderate or severe hypertension demonstrated that the
      antihypertensive efficacy of eprosartan (usually 400 to 800 mg/day as a single
      daily dose or in 2 divided doses) is significantly greater than that of placebo
      and at least as good as that of enalapril. In placebo-controlled trials,
      eprosartan achieved mean reductions from baseline in trough sitting systolic
      blood pressure of 6.3 to 15 mm Hg and in diastolic blood pressure of 4.1 to 9.7
      mm Hg. Response rates associated with once daily administration of eprosartan 400
      to 800 mg were approximately double those with placebo. Overall, eprosartan was
      well tolerated with a similar tolerability profile to that of placebo. In
      comparative trials, in which the incidence of persistent dry cough was evaluated
      as the primary end-point, enalapril was several-fold more likely to induce this
      adverse event than eprosartan (the difference being statistically significant
      regardless of study population and definition of cough). In conclusion, the
      angiotensin II receptor antagonist eprosartan is a well tolerated and effective
      antihypertensive agent that is administered once or twice daily without regard to
      meals. Eprosartan has a low potential for serious adverse events, and the drug
      has not been associated with clinically significant drug interactions. Unlike ACE
      inhibitors such as enalapril, eprosartan does not have a high propensity to cause
      persistent nonproductive cough. Thus, eprosartan represents a useful therapeutic
      option in the management of patients with hypertension.

PMID- 10929935
TI  - Dalteparin: an update of its pharmacological properties and clinical efficacy in
      the prophylaxis and treatment of thromboembolic disease.
AB  - Dalteparin is a low molecular weight heparin (LMWH) with a mean molecular weight
      of 5000. Compared with unfractionated heparin (UFH), the drug has markedly
      improved bioavailability and increased plasma elimination half-life, and exerts a
      greater inhibitory effect on plasma activity of coagulation factor Xa relative to
      its effects on other coagulation parameters. Dalteparin also has less lipolytic
      activity than UFH. Dalteparin 2500U once daily subcutaneously is of similar
      antithrombotic efficacy to UFH 5000IU twice daily, and 2 studies have shown
      superiority over UFH 2 or 3 times daily of dalteparin 5000U once daily in
      patients requiring surgical thromboprophylaxis. After total hip arthroplasty,
      dalteparin was superior to adjusted-dosage warfarin and was of greater
      thromboprophylactic efficacy when given for 35 than for 7 days. Intravenous or
      subcutaneous dalteparin is as effective as intravenous UFH when given once or
      twice daily in the initial management of established deep vein thrombosis (DVT).
      The drug is also effective in long term home treatment. Dalteparin has been shown
      to be effective in combination with aspirin in the management of unstable
      coronary artery disease (CAD), with composite end-point data from 1 study
      suggesting benefit for up to 3 months. Current data indicate potential of the
      drug in the management of acute myocardial infarction (MI). Dalteparin is also of
      similar efficacy to UFH, with a single bolus dose being sufficient in some
      patients, in the prevention of clotting in haemodialysis and haemofiltration
      circuits. Pharmacoeconomic data indicate that overall costs relative to UFH from
      a hospital perspective can be reduced through the use of dalteparin in patients
      receiving treatment for venous thromboembolism. Dalteparin has also been shown to
      be cost effective when used for surgical thromboprophylaxis. Overall, rates of
      haemorrhagic complications in patients receiving dalteparin are low and are
      similar to those seen with UFH. CONCLUSIONS: Dalteparin is effective and well
      tolerated when given subcutaneously once daily in the prophylaxis and treatment
      of thromboembolic disease. The simplicity of the administration regimens used and
      the lack of necessity for laboratory monitoring facilitate home or outpatient
      treatment and appear to translate into cost advantages from a hospital
      perspective over UFH or warfarin. Dalteparin also maintains the patency of
      haemodialysis and haemofiltration circuits, with beneficial effects on blood
      lipid profiles and the potential for prophylaxis with a single bolus injection in
      some patients. Data are also accumulating to show dalteparin to be an effective
      and easily administered alternative to UFH in patients with CAD.

PMID- 10929937
TI  - Ethylene captures a metal! Metal ions are involved in ethylene perception and
      signal transduction.
AB  - More than three decades ago, transition metal such as copper or zinc were
      postulated to be required for the ethylene perception. However, there was no
      direct evidence for this metal requirement until very recently. Two studies using
      Arabidopsis thaliana, one genetic and the other biochemical, have provided
      complementary evidence for the role of copper in ethylene perception, closing
      this argument. Additional evidence for the importance of the metal in the
      ethylene-signaling pathway came with the recent discovery that EIN2, a central
      signal transducer in the ethylene-signaling pathway, has significant homology to
      the Nramp divalent cation transporters. These studies suggest that metal
      metabolism may have a critical role not only in ethylene perception but also in
      ethylene signaling.

PMID- 10929938
TI  - Acropetal disappearance of PsAD1 protein in pea axillary buds after the release
      of apical dominance.
AB  - We recently isolated PsAD1 cDNA from pea (Pisum sativum L. cv. Alaska) seedlings,
      whose mRNA abundantly accumulated in dormant axillary buds and disappeared after
      decapitation [Madoka and Mori (2000) Plant Cell Physiol. 41: 274]. To further
      elucidate the function of PsAD1, we investigated the temporal and spatial
      distribution patterns of PsAD1 protein using Western blot and immunocytochemical
      analyses. Western blot analyses showed that accumulation patterns of PsAD1
      protein in axillary buds after decapitation and in response to IAA and 6
      benzyladenine were the same as those of PsAD1 mRNA. Immunocytochemical analyses
      showed that (1) PsAD1 proteins were localized in the procambia, leaf primordia,
      apical meristem, and secondary axillary buds in the dormant axillary bud, and
      this distribution was the same as that of PsAD1 mRNA, (2) PsAD1 proteins
      acropetally disappeared after decapitation, and (3) the growth of axillary buds
      occurred in the same manner. These acropetal changes occur in a manner similar to
      the way in which the procambium differentiates into vascular tissue. These
      results suggest that PsAD1 plays some role in the inhibition of growth and
      differentiation, or in the maintenance of the dormant state in axillary buds.

PMID- 10929939
TI  - Evidence of chlorophyll synthesis pathway alteration in desiccated barley leaves.
AB  - In etiolated leaves, saturating flash of 200 ms induces phototransformation of
      protochlorophyllide (Pchlide) F655 into chlorophyllide (Chlide), then into Chl
      through reactions which do not need light sensibilisation. The synthesis of Chl
      is known to be slowed down in etiolated leaves exposed to desiccation stress. In
      order to analyse the intensity and time-course of Chlide transformation into Chl,
      we used the fluorescence emission of etiolated leaves previously exposed to a 200
      ms saturating flash. We used low-temperature fluorescence spectroscopy to reveal
      the inhibition site of Chl synthesis in etiolated barley leaves exposed to water
      stress. Shibata shift appears as the main target point of the water deficit. It
      was found that water deficit inhibits partially active Pchlide F655 regeneration.
      Also, esterification of Chlide into Chl is impaired. It appears that these
      inhibitory effects alter the appearance of PSII active reaction centres.

PMID- 10929940
TI  - Effects of myosin ATPase inhibitor 2,3-butanedione 2-monoxime on distributions of
      myosins, F-actin, microtubules, and cortical endoplasmic reticulum in maize root
      apices.
AB  - 2,3-Butanedione 2-monoxime (BDM) is a general inhibitor of myosin ATPases of
      eukaryotic cells, and its effects on animal and yeast cells are well described.
      Using immunofluorescence and electron microscopy, we have analyzed the impacts of
      BDM on distributions of plant myosins, actin filaments (AFs), microtubules (MTs),
      and cortical endoplasmic reticulum (ER) elements in various cell types of maize
      root apices. Treatment of growing maize roots with BDM altered the typical
      distribution patterns of unconventional plant myosin VIII and of putative maize
      homologue(s) of myosin II. This pharmacological agent also induced a broad range
      of impacts on AFs and on cortical ER elements associated with plasmodesmata and
      pit fields. BDM-mediated effects on the actomyosin cytoskeleton were especially
      pronounced in cells of the root transition zone. Additionally, BDM elicited
      distinct reactions in the MT cytoskeleton; endoplasmic MTs vanished in all cells
      of the transition zone and cortical MTs assembled in increased amounts
      preferentially at plasmodesmata and pit-fields. Our data indicate that AFs and
      MTs interact together via BDM-sensitive plant myosins, which can be considered as
      putative integrators of the plant cytoskeleton. Morphometric analysis revealed
      that cell growth was prominently inhibited in the transition zone and the apical
      part, but not the central part, of the elongation region. Obviously, myosin-based
      contractility of the actin cytoskeleton is essential for the developmental
      progression of root cells through the transition zone.

PMID- 10929941
TI  - Over-expression of tobacco knotted1-type class1 homeobox genes alters various
      leaf morphology.
AB  - We compared the phenotypes of transgenic tobacco plants over-expressing various
      knotted1-type class1 homeobox genes. All transformants showed abnormal leaf
      morphology, with the degree of abnormality depending upon the Nicotiana tabacum
      homeobox (NTH) gene that was over-expressed. Tobacco plants over-expressing NTH1
      or NTH9 showed a relatively weak phenotype, while NTH15 and NTH20 over-expressing
      plants exhibited severe alterations, with occasional ectopic shoot formation on
      the leaves. Plants over-expressing NTH22 had a relatively severe phenotype, but
      did not form any ectopic shoots. These results indicate that all of the NTH genes
      can influence leaf development from the shoot apical meristem, but that the
      effect varies with the gene. Based on phylogenetic analysis of the NTH genes and
      comparison of the phenotypes of plants over-expressing them, we suggest that the
      kn1-type class1 family can be divided into two subgroups, and that the
      differences in their ability to induce the abnormal phenotype corresponds to the
      structures of their conserved domains.

PMID- 10929942
TI  - Characterization of three forms of light-harvesting chlorophyll a/b-protein
      complexes of photosystem II isolated from the green alga, Dunaliella salina.
AB  - Three forms of light-harvesting chlorophyll a/b-protein complexes of photosystem
      II (LHC II) were isolated from the thylakoid membranes of Dunaliella salina grown
      under different irradiance conditions. Cells grown under a low intensity light
      condition (80 micromol quanta m(-2) s(-1)) contained one form of LHC II, LHC-L.
      Two other forms of LHC II, LHC-H1 and LHC-H2, were separated from the cells grown
      under a high intensity light condition (1,500 micromol quanta m(-2) s(-1)). LHC-L
      and LHC-H1 showed an apparent particle size of 310 kDa and contained four
      polypeptides of 31, 30, 29 and 28 kDa. LHC-H2, with a particle size of 110 kDa,
      consisted of 30 and 28 kDa polypeptides. LHC-L contained 7.5 molecules of Chl a,
      3.2 of Chl b and 2.1 of lutein per polypeptide, analogous to the content in
      higher plants. LHC-H1, with 5.6 molecules of Chl a, 2.5 of Chl b and 1.8 of
      lutein per polypeptide was similar to that in the green alga Bryopsis maxima. LHC
      L and LHC-H1 maintained high efficiency energy transfer from Chl b and lutein to
      Chl a molecules. LHC-H2 showed a high Chl a/b ratio of 7.5 and contained 3.4
      molecules of Chl a, 0.5 of Chl b and 1.4 of lutein per polypeptide. Chl b and
      lutein could not completely transfer the excitation energy to Chl a in LHC-H2.

PMID- 10929943
TI  - Changes in tubulin protein expression in guard cells of Vicia faba L. accompanied
      with dynamic organization of microtubules during the diurnal cycle.
AB  - We previously reported that the organization of microtubules (MTs) in guard cells
      of Vicia faba L. shows dynamic diurnal changes [Fukuda et al. (1998) Plant Cell
      Physiol. 39: 80]. Here, we report a method to directly extract total proteins
      from guard cells to investigate the biochemical changes in guard cells of Vicia
      faba L. during the diurnal cycle. Electrophoretic profiles of total proteins of
      guard cells showed distinct patterns with the time of extraction. Immunoblot
      analysis also demonstrated changes in alpha-tubulin and beta-tubulin contents
      with the diurnal cycle. Both tubulins were abundant at 6:00 h and 12:00 h but
      were almost undetectable at 24:00 h. Although treatment with either actinomycin D
      or cycloheximide at 18:00 h inhibited neither radial organization of cortical MTs
      nor stomatal opening, that at 6:00 h inhibited both. These results suggest that
      the dynamic diurnal changes in the organization of MTs in guard cells and
      stomatal movement of Vicia faba L. may be, at least partly, regulated by de novo
      synthesis and decomposition of tubulin molecules in guard cells.

PMID- 10929944
TI  - The ethylene-regulated expression of CS-ETR2 and CS-ERS genes in cucumber plants
      and their possible involvement with sex expression in flowers.
AB  - It has been reported that ethylene production by cucumber plants is strongly
      related to the sex expression of their flowers. It has also been shown that both
      CS-ACS2 gene expression and ethylene evolution are much greater in gynoecious
      cucumber plants than monoecious ones. To investigate the action mechanism of
      ethylene in the induction of femaleness of cucumber flowers, we isolated three
      ethylene-receptor-related genes, CS-ETR1, CS-ETR2 and CS-ERS, from cucumber
      (Cucumis sativus L.) plants. Of these three genes, CS-ETR2 and CS-ERS mRNA
      accumulated more substantially in the shoot apices of the gynoecious cucumber
      than those of the monoecious one. Their expression patterns correlated with the
      expression of the CS-ACS2 gene and with ethylene evolution in the shoot apices of
      the two types of cucumber plants. Accumulation of CS-ETR2 and CS-ERS mRNA was
      significantly elevated by the application of Ethrel, an ethylene-releasing agent,
      to the shoot apices of monoecious cucumber plants. In contrast, the accumulation
      of their transcripts was lowered when aminoethoxyvinyl glycine (AVG), an
      inhibitor of ethylene biosynthesis, was applied to the shoot apices of gynoecious
      cucumber plants. Thus, the expression of CS-ETR2 and CS-ERS is, at least in part,
      regulated by ethylene. The greater accumulation of CS-ETR2 and CS-ERS mRNA in
      gynoecious cucumber plants may be due to the higher level of endogenous ethylene,
      which plays a role in the development of female flowers.

PMID- 10929945
TI  - Characterization of the arabidopsis formin-like protein AFH1 and its interacting
      protein.
AB  - A partial cDNA encoding an Arabidopsis thaliana FH (Formin Homology) protein
      (AFH1) was used as a probe to clone a full length AFH1 cDNA. The deduced protein
      encoded by the cDNA contains a FH1 domain rich in proline residues and a C
      terminal FH2 domain which is highly conserved amongst FH proteins. In contrast to
      FH proteins of other organisms, the predicted AFH1 protein also contains a
      putative signal peptide and a transmembrane domain suggesting its association
      with membrane. Cell fractionation by differential centrifugation demonstrated the
      presence of AFH1 in the Triton X-100 insoluble microsomal fraction. An
      Arabidopsis cDNA library was screened to identify proteins that interact with the
      C-terminal region of AFH1 using yeast two-hybrid assays, and one of the isolated
      cDNAs encoded a novel protein, FIP2. Experiments using recombinant proteins
      expressed in E. coli demonstrated that FIP2 interacted directly with AFH1. The
      amino acid sequence of FIP2 has partial homology to bacterial putative membrane
      proteins and animal A-type K+ ATPases. AFH1 may form a membrane anchored complex
      with FIP2, which might be involved in the organization of the actin cytoskeleton.

PMID- 10929946
TI  - Vascular tissue-specific gene expression of xylem sap glycine-rich proteins in
      root and their localization in the walls of metaxylem vessels in cucumber.
AB  - Root-specific cDNAs of glycine-rich protein (cucumber root glycine rich protein-1
      and -2; CRGRP-1 and CRGRP-2) were cloned previously by use of an antiserum raised
      against whole xylem sap of Cucumis sativus. The accumulation of the corresponding
      mRNA at high levels was detected in the root-hair zone of cucumber tap root
      [Sakuta et al. (1998) Plant Cell Physiol. 39: 1330]. The RNA gel blot analysis
      with the CRGRP-1- and -2-specific probes revealed that the CRGRP genes expressed
      only in root but not at all in aboveground organs. When the localization of these
      mRNAs were examined by in situ hybridization, CRGRP mRNAs were found only in the
      parenchyma cells in the central cylinder of young lateral roots and it was most
      abundant in the cells that surrounded xylem vessels in the root-hair zone of the
      tap root. In immunoblotting of xylem sap collected from cucumber stem with an
      antiserum raised against CRGRP-1 that had been produced in an E. coli expression
      system, the antibodies, which did not cross-react with GRP1.8 of kidney bean,
      reacted with two proteins, whose mobilities corresponded to those of proteins
      deduced from the CRGRP-1 and -2 cDNAs. Immunohistochemical staining revealed that
      the CRGRPs accumulated specifically in the lignified walls of metaxylem vessels
      in the root, stem and leaf and in the lignified cell walls of perivascular fibers
      in cucumber stems. Immunostaining was also detected in the walls of metaxylem
      vessels and in the cell walls of adjacent sclerenchyma in the hypocotyl of kidney
      bean. These data clearly indicate that the novel glycine-rich proteins were
      produced in the vascular tissue of the root, transported systemically over a long
      distance via the xylem sap and immobilized in the walls of metaxylem vessels and
      sclerechyma cells in aboveground organs.

PMID- 10929947
TI  - Tissue-specific localization of mRNA for carrot homeobox genes, CHBs, in carrot
      somatic embryos.
AB  - We examined spatial and temporal expression patterns of four carrot HD-Zip I
      homeobox genes in somatic embryos. The mRNAs for CHB3, CHB4 and CHB5 were
      accumulated preferentially in the innermost cortical cell layers of the embryo
      axis in the torpedo-shaped embryo. In contrast, the accumulation of CHB6 mRNA was
      restricted to procambial cells of the heart- and torpedo-shaped embryos. In the
      embryonic cotyledons and the hypocotyl of the seedlings, all of the mRNAs for the
      four genes were located in the vascular tissues. These findings indicate that
      different HD-Zip I homeobox genes may be involved in the differentiation of
      specific tissues during somatic embryogenesis.

PMID- 10929948
TI  - Action spectra of DNA photolyases for photorepair of cyclobutane pyrimidine
      dimers in sorghum and cucumber.
AB  - DNA photolyases that catalyze light-dependent repair of cyclobutane pyrimidine
      dimers (CPDs) were extracted and partially purified from sorghum and cucumber.
      The action spectra of CPD photolyases in these plant species had a maximum at 400
      nm, which differ from those in Drosophila, Escherichia coli and Anacystis.

PMID- 10929949
TI  - Octreotide inhibits myeloperoxidase activity in rat uterus.
AB  - OBJECTIVE: Several studies have demonstrated that synthetic somatostatin-analog
      octreotide could affect the functions of the hypothalamus, anterior pituitary
      gland and ovary. To date, very few studies on the effect of octreotide on uterine
      function have been reported. We investigated the effects of octreotide on
      neutrophil functions in rat uterus. METHODS: Twenty Sprague-Dawley rats were
      subjected to a standardized uterine horn excision. To evaluate the effect of
      octreotide, the rats were assigned randomly to treatment (octreotide 20
      microgr/kg, SC) and control groups. After two weeks relaparotomy was performed
      and contralateral uterine horns were excised in the same standardized manner. The
      excised segment was washed in cold saline solution and was frozen in liquid
      nitrogen immediately and homogenized. Myeloperoxidase (MPO) and elastase
      concentrations were determined in homogenates of uterine horns. The data were
      analyzed by Mann-Whitney U test. RESULTS: In octreotide-treated rats the MPO
      activity was significantly reduced after 14 days (14.79+/-2.08 versus 6.62+/-1.72
      U/mg protein; p=0.012). There was also a significant difference in mean MPO
      levels between the two groups at the end of the experiment (6.62+/- 1.72 versus
      18.56+/-2.49 U/mg protein; p=0.001). The octreotide administration did not affect
      elastase levels significantly. No differences were found in mean elastase levels
      in both groups after the treatment. CONCLUSION: This study demonstrates that
      octreotide has a significant effect on the neutrophil function in terms of MPO
      activity in rat uterus. Further studies are needed to clarify the clinical
      relevance of the inhibitory effect of octreotide in the uterus and the
      possibility of its applications.

PMID- 10929950
TI  - Neurochemical and cellular markers in human cervix of late pregnant, postpartal
      and non-pregnant women.
AB  - BACKGROUND: The aim was to evaluate the peptidergic innervation and the dendritic
      cell content in the cervix uteri. METHODS: Cervical biopsies were obtained from
      late pregnant (n=5), postpartal (n=5) and non-pregnant (n=5) women. The samples
      were prepared for immunohistochemistry using antibodies to protein S-100 (S-100),
      calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP),
      human peptide histidine isoleucine amide (PHM 27), neuropeptide tyrosine (NPY),
      and human histocompatibility complex class II subregion DR (HLA-DR). RESULTS:
      Nerve fibers positive for protein S-100, and dendritic cells positive for S-100
      and HLA-DR were abundant in the cervix, especially at late pregnancy. CGRP, VIP,
      PHM-27 and NPY positive nerve fibers were present in non-pregnant, short nerve
      fibers and scattered immunoreactivity at term, and further scattered
      immunoreactivity after parturition. NPY positive nerve fibers were decreased at
      term, and after parturition a scattered immunoreactivity was observed.
      CONCLUSIONS: The abundant protein S-100 positive nerve fibers implies an impact
      of myelinated nerves in the cervix uteri during pregnancy. The abundant dendritic
      cells, positive for HLA-DR and S-100, especially at term, indicates a general
      activation of the immune system until late pregnancy and parturition. The changed
      occurrence and distribution of immunoreactivity for CGRP, VIP and PHM-27 suggest
      a release of these neuropeptides until term. The changes in NPY immunoreactivity
      indicate a release of NPY around parturition.

PMID- 10929951
TI  - Epidural analgesia with sufentanil during labor and operative delivery.
AB  - BACKGROUND: It has been argued that by adding an opioid to the local anesthetic
      drug used for epidural analgesia during childbirth, one can reduce the risk of
      operative delivery. Objective. In a population-based observational study, to
      evaluate the effect of adding an opioid to a local anesthetic drug on the risk of
      instrumental delivery or cesarean section. DESIGN: Comparison of delivery units
      adding/not adding opioid to the local anesthetic for epidural analgesia in labor.
      SETTING: All deliveries using epidural analgesia in Sweden during 1992-96 were
      evaluated on the basis of information stored at the Medical Birth Registry, the
      National Board of Health and Welfare, Stockholm. METHOD: A questionnaire was sent
      to all delivery units (n=61), as well as to the Head of corresponding
      Anesthesiology Department in each hospital, requesting information regarding the
      period when opioids (sufentanil) were first added to the local epidural
      analgesic. Parturients given epidural analgesia were divided into three time
      related groups: those delivered before the introduction of opioids (n=34,071),
      when opioids were first added (n=7,236), and since the introduction of opioids
      (n=44,384). Odds ratio (OR) with 95% confidence interval (CI) was used to assess
      the effect of sufentanil versus no sufentanil, on the risk of operative delivery.
      The parturients were stratified for year of delivery, age, and parity. Main
      outcome measures. Instrumental delivery, cesarean section, length of stay in
      hospital post partum. RESULTS: A significant reduction was observed in the
      incidence of instrumental delivery (OR 0.72; 95% CI 0.68-0.76). A similar though
      less pronounced effect was evident concerning the risk of cesarean section for
      nulliparae (OR 0.79; 95% CI 0.72-0.88) but not for multiparae (OR 0.93; 95% CI
      0.80-1.07). Fewer women with an opioid added to the local anesthetic spent more
      than 4 (or more than 7) days in hospital post partum, compared with those given
      epidural analgesia without an opioid. CONCLUSION: When added to the local
      anesthetic used for epidural analgesia, as in Sweden during the last 5 years,
      opioids appear to reduce the incidence of instrumental delivery and cesarean
      section and also the post partum hospital stay.

PMID- 10929952
TI  - Obstetric risks and vertical transmission of hepatitis C virus infection in
      pregnancy.
AB  - BACKGROUND: Reports of obstetric complications of mothers infected with hepatitis
      C virus (HCV) are limited and the risk of mother-to-infant transmission varies
      widely. We assessed the course of pregnancy in HCV-infected women and the rate of
      vertical transmission. METHODS: Between October 1992 and December 1996, 3712
      pregnant patients of the university hospital Grosshadern Munich, Germany, were
      screened for anti-HCV and analyzed for HCV-RNA by polymerase chain reaction.
      Clinical and biochemical parameters were monitored. Children born to HCV-positive
      women were followed up at 6, 12 and 18 month intervals and screened for anti-HCV
      and HCV-RNA. RESULTS: Thirteen (42%) of 31 anti-HCV positive patients had a
      cesarean section which was twice the rate of that in the HCV-negative group
      (p=0.004). None of the cesarean deliveries was due to complications directly
      caused by HCV infection. Nine (29%) of 31 anti-HCV positive women had preterm
      delivery compared to 19% in the anti-HCV negative patients, the difference being
      statistically not significant. Fetal outcome parameters such as APGAR score,
      umbilical pH and birth weight of HCV infected pregnancies were not impaired. All
      29 babies tested for anti-HCV were seropositive after birth. Between 12 and 18
      months of age, 10% of the infants still were anti-HCV positive, whereas only one
      baby was HCV-RNA positive beyond 12 months yielding a vertical transmission rate
      of 5% among HCV-RNA positive mothers. CONCLUSION: Anti-HCV positive pregnancies
      have an increased risk of cesarean delivery, probably due to the high-risk
      collective of anti-HCV positive mothers. The mother-to-child transmission rate is
      low and linked to maternal HCV-RNA positivity.

PMID- 10929953
TI  - Intrahepatic cholestasis of pregnancy has no effect on maternal serum second
      trimester alpha-fetoprotein and hCG.
AB  - OBJECTIVE: To investigate the association between intrahepatic cholestasis and
      Down's syndrome screening analytes (alpha-fetoprotein [AFP] and hCG) during the
      second trimester. DESIGN: Measurements of maternal serum AFP and hCG
      concentrations were retrospectively analyzed in relation to intrahepatic
      cholestasis in a cohort of 33 consecutive singleton pregnancies affected by
      cholestasis from January 1995 through December 1997 at the University Hospital of
      Kuopio, and then compared with those in healthy singleton control pregnancies
      (n=5680) from the same clinic over the same period of time. RESULTS: Geometric
      means of maternal serum AFP and hCG concentrations in pregnancies affected by
      cholestasis were 1.12 and 0.98 multiples of the median [MoM], respectively. Mean
      maternal age was significantly higher in the subjects than in controls (30.6
      years compared with 28.8 years). In relation to Down's syndrome risk assessment,
      the pattern of the two markers together with maternal age indicated high risk as
      often in the study subjects as in the controls. CONCLUSION: Median serum AFP and
      hCG concentrations in pregnancies complicated by intrahepatic cholestasis were
      not significantly different from those in unaffected pregnancies. There is no
      need to take the hepatic disorder into account in maternal serum screening.

PMID- 10929954
TI  - Cesarean section among immigrants in Norway.
AB  - OBJECTIVE: We studied prevalences and risk factors for cesarean section among
      different groups of immigrants from countries outside Western Europe and North
      America in comparison to ethnic Norwegians. METHODS: The study is population
      based using data from the Medical Birth Registry of Norway. A total of 553,491
      live births during the period 1986-1995 were studied, including 17,891 births to
      immigrant mothers. RESULTS: The prevalences of cesarean section ranged from 10.1%
      among women from Vietnam to 25.8% in the group of Filipino origin. The use of
      abdominal delivery was also high in the groups from Sri Lanka/India (21.3%),
      Somalia/Eritrea/Ethiopia (20.5%) and Chile/Brazil (24.3%), while the frequency
      among women from Turkey/Morocco (12.6%) and Pakistan (13.2%) was approximately
      the same as among ethnic Norwegians (12.4%). Feto-pelvic disproportion, fetal
      distress and prolonged labor were the most important diagnoses associated with
      the high prevalences, but the significance of these diagnoses differed among the
      groups. Other unknown factors come into play, particularly among women from
      Somalia/Eritrea/Ethiopia and Chile/Brazil. CONCLUSION: There was substantial
      variation in the use of cesarean section among ethnic groups in Norway. The
      diagnoses feto-pelvic disproportion, fetal distress and prolonged labor may be
      confounded by a number of factors including maternal request for cesarean section
      and difficulties in handling the delivery. Further research is needed to explain
      the observed differences.

PMID- 10929955
TI  - The role of DNA strand breaks in human spermatozoa used for IVF and ICSI.
AB  - BACKGROUND: The objective of this study was to determine the incidence of
      spermatozoa with DNA strand breaks in four clinically different groups of
      infertile couples, and to correlate DNA damage with other semen analysis
      parameters, as well as fertilization rates and IVF outcome. METHODS: One group
      consisted of 75 men where the female partners had a tubal obstruction, Group A.
      Fifty sperm samples were collected from men in unexplained infertile couples,
      Group B. Fifty men with oligozoospermia and IVF made up Group C. Finally, 61 men
      with oligozoospermia and where ICSI was performed made up Group D. Sperm samples
      were assessed according to the WHO manual and for the presence of DNA strand
      breaks in spermatozoa. The study was blinded for the technician involved in the
      assessment of DNA strand breaks. IVF was carried out according to a long down
      regulation protocol using GnRH, FSH and hCG. Embryos were transferred on day 2
      after fertilization with a maximum of three embryos. RESULTS: This study
      demonstrated a negative correlation between the proportion of spermatozoa having
      DNA strand breaks and the proportion of oocytes fertilized after IVF (p<0.01).
      Furthermore, the number of spermatozoa with DNA strand breaks was important for
      the pregnancy rate in the group of unexplained infertile couples. After ICSI no
      association was found between spermatozoa with DNA strand breaks and
      fertilization rates (p>0.05). CONCLUSION: DNA strand breaks in human spermatozoa
      impairs fertilization in both unexplained infertile couples and those with
      oligozoospermia and IVF. However, after ICSI, this impact of DNA strand breaks
      were not seen. This creates a specific indication and treatment for this new
      diagnosed group of otherwise unexplained infertile men.

PMID- 10929956
TI  - Circulating levels of nitric oxide in successful and unsuccessful implantation
      after in vitro fertilization and embryo transfer. Relationship to estradiol and
      progesterone.
AB  - BACKGROUND: Nitric oxide (NO) may play an important role in embryo implantation
      and early embryo development. This study investigated the potential role of
      circulating nitric oxide (NO) measurement to predict the outcome of implantation
      and pregnancy after IVF and ET. METHODS: Two blood samples were collected from
      237 IVF patients on days 13-14 and 20-21 after ET. Serum concentration of
      nitrite/nitrate (the two stable oxidation products of NO metabolism), estradiol
      (E2), progesterone and beta-hCG were measured on days 13-14 after ET and one week
      later. RESULTS: No significant differences were found with respect to
      nitrite/nitrate serum concentrations in conception versus non-conception cycles,
      viable versus abnormal pregnancies, and viable pregnancy group versus non
      conception cycles, respectively, despite that significant differences were
      observed regarding E2 and progesterone values. Nitrite/nitrate serum
      concentrations were similar for singleton and multiple pregnancies at both study
      points. In viable pregnancies, no significant change was observed for
      nitrite/nitrate serum concentration from days 13-14 to 20-21 after ET. No
      correlation was found between nitrite/nitrate serum concentration and E2 or
      progesterone serum levels. CONCLUSIONS: Circulating levels of nitrite/nitrate are
      similar in successful and unsuccessful implantation after IVF and are unrelated
      to the outcome of pregnancy. This precludes the use of serum NO measurement as a
      marker of implantation and successful pregnancy in IVF.

PMID- 10929957
TI  - Use of PCR for the detection of genital Chlamydia trachomatis infection on self
      obtained mailed vaginal samples.
AB  - BACKGROUND: To determine whether the patient self-obtained and mailed vaginal
      sample might be used for the detection of genital C. trachomatis infection by the
      PCR. METHODS: Women with genital symptoms, younger than 35 years of age and
      sexually active were enrolled. Cervical and urethral samples collected by the
      physician were tested by PCR and cell culture. Three vaginal samples were
      collected: the first and second - by the physician and the patient at the time of
      the visit to the clinic. The third vaginal sample was collected by the patient at
      home and posted dry to the laboratory. All vaginal samples were PCR-tested,
      including also the internal control for the detection of the inhibitors. RESULTS:
      The prevalence of chlamydial infection was 19.2%. C. trachomatis was detected in
      the cervix of 18.5%, in the urethra of 4.4% and in the vagina of 19.2% of the
      women, when all vaginal samples were considered. Each separate vaginal sampling
      detected 88.8% of the C. trachomatis infected women. Nearly 10% of the cervical,
      3% of the urethral and 12-19% of the vaginal samples were inhibitory. Inhibitors
      were destroyed by storage of the samples for five days at +4 degrees C or the
      dilution at 1:10. CONCLUSIONS: Self-collected and mailed vaginal sample is
      convenient for the patient and useful for the PCR-testing for genital C.
      trachomatis infections. Sensitivity of sampling might improve if several
      consecutive samples were to be collected. This self-sampling approach would help
      to reach section of the population in which pelvic examination and cervical
      sampling is not routinely performed.

PMID- 10929958
TI  - Risk of cervical cancer subsequent to a positive screening cytology: follow-up
      study in Finland.
AB  - BACKGROUND: The purpose of the study was to estimate subsequent incidence of
      cervical cancer among women with positive cytology followed by negative
      histology. METHODS: This was a longitudinal cohort study involving about 80,000
      women with class II, III, IV or V cytology at the organized mass screening in
      Finland in 1971 1990. Follow-up through the Finnish Cancer Registry started from
      the fifth month following the initial screening and ended on December 31, 1995.
      RESULTS: Standardized incidence ratios (SIR) of invasive cervical cancer varied
      from 2.2 (class II) to 19 (class V), and SIRs of preinvasive lesion varied from
      3.0 (class II) to 20 (class V) compared to the risk among the total Finnish
      female population of same age and calendar period. The relative risk was greatest
      during first years of follow-up for both preinvasive and invasive cervical
      lesions, and it remained significantly high over 5 years of follow-up. For women
      with class II cytology there were peaks in relative risk in the years of
      subsequent rescreenings. CONCLUSION: Women with positive cytology have a high
      relative risk of cervical cancer even when excluding the cancers found at
      screening; the high relative risk is persistent for more than 5 years, and
      therefore these women should be kept under close surveillance and repeated smears
      should be taken with relatively short intervals.

PMID- 10929959
TI  - Oral contraceptive failures among women terminating their pregnancy.
AB  - BACKGROUND: There are several methodological problems when studying contraceptive
      efficacy. The present study focuses on efficacy issues from the use of oral
      contraceptives (OC). METHODS: Through a computerized system of medical records
      kept at the Department of Gynecology, Regional Hospital of Trondheim, Norway, 800
      OC-failure pregnancies were identified among 8192 women having pregnancy
      termination from January 1, 1987 to December 31, 1996. Ascertainment of cases was
      done by validating hospital data on OC failures by data collected by the
      referring practitioner. Inconsistencies in failure data were found among 257 of
      the 800 (32%) women who claimed at the hospital that an OC was in use at time for
      conception. The medical record kept by their practitioners stated that 158 women
      had stopped using OC before last menstrual period, of the remaining 99 women
      neither data on actual use nor data on prescription could be confirmed. RESULTS:
      Over the 10-year study period the proportion of failures by brand of OC was
      remarkably constant from year to year and reflected the user pattern of OCs in
      Norway. One-third of the total number of failures (n=523) were claimed to be
      method failures. The annual overall OC-failure rate was estimated to be 1% during
      the 10-year study. CONCLUSION: Case-control studies focusing on efficacy of OCs
      must be carefully designed and comprise both women carrying a pregnancy to term
      as well as women terminating their pregnancies. Our study focused on only one
      segment of the population of women experiencing an OC failure: women having
      pregnancy termination. The present study has shown that exposure data collected
      from interviews have to be validated against prescription data.

PMID- 10929960
TI  - Factors associated with cone margin involvement in CIN patients undergoing
      conization-equivalent electrosurgical procedure.
AB  - BACKGROUND: Most studies of cervical conization have considered the frequency of
      complications and the outcome of follow-up. The determinants of cone margin
      positivity have been inadequately described. In a series of CIN patients
      undergoing conization-equivalent electrosurgical procedure, we evaluated the
      factors associated with (i) any cone margin involvement, and (ii) endocervical
      margin involvement (with or without other locations) as contrasted with all other
      conditions. METHODS: Study population included 718 patients. Potential
      determinants of margin involvement were or were treated as categorical.
      Univariate analysis was based on the chi-square test. Multivariate associations
      were estimated by multiple logistic regression models. RESULTS: Cone margin
      involvement was observed in a total of 195 patients (27%). In univariate
      analysis, the frequency was positively related to histologic grade, time period,
      lesion size, and cone width and depth. In multivariate analysis, histology
      diagnosis and time period retained a strong association. The effect of lesion
      size was of borderline significance. The endocervical location emerged as a
      multivariate determinant of margin positivity. The effect of cone width and depth
      was not confirmed. Endocervical margin involvement was observed in 98 cases
      (14%). In univariate analysis, the frequency was positively associated with
      histologic grade, time period, and age, and inversely related to the visibility
      of the squamous-columnar junction. Multivariate analysis confirmed the strong
      effect of histology diagnosis and time period. The association with age and
      visibility of the squamous-columnar junction was weaker. CONCLUSIONS: Histology
      diagnosis and time period were the strongest determinants of cone margin
      involvement. Endocervical margin positivity was also related to patient age and
      visibility of the squamous-columnar junction. Cone width and depth had no
      protective effect.

PMID- 10929961
TI  - Feasibility and pain control in outpatient hysteroscopy in postmenopausal women:
      a randomized trial.
AB  - BACKGROUND: Three methods of diagnostic hysteroscopy have been tested for both
      women's compliance and feasibility of procedures in postmenopause. METHODS: Three
      hundred and sixty-two postmenopausal women were enrolled in a three-arm study: 5
      mm diagnostic sheath (Group 1, 119 women), 5 mm sheath with paracervical block
      (Group 2, 121 women), and 3.5 mm sheath (Group 3, 121 women). CO2 was the
      distention medium. Both feasibility of hysteroscopy (procedures failed due to
      stenosis or incomplete distention of cavity) and discomfort of women have been
      recorded. Pain perception has been measured on a visual numerical rating scale.
      Statistical analysis was performed by t-test for unpaired samples and chi-square
      test. RESULTS: Paracervical block was per se painful in 18.2% and bleeding from
      injection site occurred in 38.8%. Hysteroscopy failure due to stenosis occurred
      in 9%, 10% and 0.4% of the three groups respectively (p<0.01). Intolerable pain
      was reported by 17% of women in Group 1, 6% in Group 2 (p<0.05) and in none of
      Group 3 (p<0.01). Pain score improved from Group 1 to Group 3 (p<0.01).
      Hysteroscopy was incomplete because of gas leakage in 1.7% of both Group 1 and 2
      and in 13.2% of Group 3 (p<0.01). CONCLUSIONS: Pain perception in postmenopausal
      women was reduced when paracervical block was used, but discomfort was even less
      with the narrow sheath hysteroscope. The narrow sheath will expose to a high
      percentage of inconclusive procedures but it can be overcome by changing to the
      large sheath hysteroscope without affecting patient pain perception.

PMID- 10929962
TI  - Randomized controlled trial on the effect of pelvic floor muscle training on
      quality of life and sexual problems in genuine stress incontinent women.
AB  - BACKGROUND: The purpose of the present study was to evaluate the effect of pelvic
      floor muscle exercise on quality of life, lifestyle and sex-life variables in
      genuine stress incontinent women. METHODS: Fifty-nine women with clinically and
      urodynamically proven genuine stress incontinence were randomized to either
      pelvic floor muscle exercise or an untreated control group. The intervention
      group was asked to perform 8-12 close to maximum contractions in 3 series per
      day. In addition they were exercising 45 minutes per week in groups. The
      intervention period was 6 months, and the women in the exercise group met once a
      month for individual assessment of pelvic floor muscle strength and motivation.
      Outcome measures were the Norwegian version of the Quality of Life Scale (QoLS-N)
      and the Bristol Female Lower Urinary Tract Symptoms (B-FLUTS) questionnaire.
      RESULTS: The results showed that general quality of life measured by the generic
      quality of life questionnaire was not much affected by urinary incontinence.
      However, the disease specific questionnaire demonstrated that ability to
      participate in physical activity and some sex-life variables were affected by the
      condition. There was a statistically significant (p<0.01) reduction in number of
      women having problems with sex-life, social life, and physical activity in the
      exercise group after six months of pelvic floor muscle exercise. CONCLUSION:
      Pelvic floor muscle exercise showed some effect on quality of life and sex-life
      variables.

PMID- 10929963
TI  - The effect of tamoxifen on the endometrium, serum lipids and hypothalamus
      pituitary axis in the postmenopausal breast cancer patients.
AB  - BACKGROUND: There is still no cost-effective endometrial screening method for
      asymptomatic postmenopausal breast cancer patients using tamoxifen. We
      investigated the effectivity of transvaginal ultrasonography and endometrial
      sampling as a screening method for asymptomatic patients. Additionally the effect
      of tamoxifen on hypothalamus-pituitary axis and serum lipid profiles were
      investigated. METHODS: Sixty-seven gynecologically asymptomatic postmenopausal
      breast cancer patients were enrolled in this randomized crossover study.
      Endometrial thickness was determined by transvaginal ultrasonography, endometrial
      biopsy was obtained by Pipelle or fractional curettage, hormone and lipid
      profiles were compared in the two groups which consisted of forty-seven tamoxifen
      user (cases) and twenty nonuser (controls) patients. RESULTS: The mean
      endometrial thickness measured by transvaginal sonography was 7.8 mm (3-20 mm)
      versus 3.7 mm respectively. The difference was significant in tamoxifen users.
      The most common histopathologic finding was endometrial polyp, detected in five
      patients. In the control group there was no endometrial polyp. The positive
      histopathologic findings were present in twenty-two patients in the case group
      but there were only two patients with positive histopathologic findings in the
      control group. Ultrasound findings did not correlate with the presence of
      endometrial abnormalities on biopsy and no endometrial cancer or hyperplasia were
      detected. In tamoxifen users serum FSH and LH levels were significantly lower
      than in nonusers. Serum HDL levels were significantly higher in the case group.
      CONCLUSION: Ultrasonographic imaging of the endometrium in asymptomatic
      postmenopausal breast cancer patients using tamoxifen should be interpreted with
      caution. Other imaging techniques should be used for more specific information
      about the endometrium.

PMID- 10929964
TI  - The effects of gonadotropin-releasing hormone agonist on body composition in a
      patient with polycystic ovary syndrome.

PMID- 10929965
TI  - Starch peritonitis outbreak after introduction of a new brand of starch powdered
      latex gloves.

PMID- 10929966
TI  - Angiomyofibroblastoma of the vulva: a rare but distinct entity.

PMID- 10929967
TI  - Hematocolpos secondary to imperforate hymen, contribution of transrectal
      echography.

PMID- 10929968
TI  - Intravaginal foreign body of over 25 years' duration.

PMID- 10929969
TI  - Nifedipine versus ritodrine for suppression of preterm labor; a meta-analysis.

PMID- 10929970
TI  - Use of supplement iron in pregnancy.

PMID- 10929972
TI  - Three-dimensional characteristics of macular pseudoholes using confocal laser
      tomography.
AB  - BACKGROUND: Epiretinal membranes with macular pseudoholes are sometimes confused
      with full-thickness macular holes. Because both the natural course and clinical
      management of the two differ, an accurate differential diagnosis is needed.
      PATIENTS AND METHODS: We obtained three-dimensional images of macular pseudoholes
      in 12 eyes using the Heidelberg retina tomograph (HRT). Another 15 eyes with a
      full-thickness macular hole were also studied. In addition, we measured the area
      and the maximum depth of both types of holes. RESULTS: Irregular rippling
      undulations were frequently observed on the three-dimensional topographic maps
      around the pseudoholes, whereas elevated cuffs were observed around the full
      thickness holes. The maximum depth of the macular pseudoholes (mean, 57 microm)
      was significantly shallower than that of the full-thickness macular holes (mean,
      156 microm; P < 0.01). CONCLUSION: Three-dimensional images obtained by the HRT
      and the measurement of the maximum depth may be useful in differentiating macular
      pseudoholes from full-thickness macular holes.

PMID- 10929971
TI  - Pneumatic buckle for the repair of primary rhegmatogenous retinal detachment.
AB  - OBJECTIVES: This prospective study examines the effectiveness of the pneumatic
      buckle procedure (nondrainage scleral buckle with pneumatic retinopexy) for
      repair of primary rhegmatogenous retinal detachments. METHODS: We studied 58
      consecutive patients with primary rhegmatogenous retinal detachments who
      underwent a pneumatic buckle with air or SF6. The procedures were performed at 2
      centers. Retinal reattachment and visual acuity were examined. RESULTS: The
      single operation reattachment rate for patients undergoing a pneumatic buckle
      procedure was 95%. Eighty eight percent of patients with macula-on detachment had
      unchanged or improved final visual acuity. Sixty seven percent of patients with
      macula-off detachments had a final visual acuity between 20/20 and 20/50. Twenty
      nine percent had final visual acuity between 20/60 and 20/200. Two patients
      developed a new retinal hole postoperatively. CONCLUSION: Pneumatic buckle is an
      effective technique for repair of primary rhegmatogenous retinal detachments
      caused by breaks in the superior 8 o'clock segment. This technique avoids the
      complications associated with the drainage portion of the traditional scleral
      buckle operation and results in a high rate of retinal reattachment and stable or
      improved visual acuity. The rate of new retinal hole formation in this study is
      much lower than those reported for pneumatic retinopexy.

PMID- 10929975
TI  - Corneal endothelial cell loss after multiple vitreoretinal procedures and the use
      of silicone oil.
AB  - BACKGROUND AND OBJECTIVE: Corneal decompensation and complications are a frequent
      cause of visual loss after vitreoretinal surgery. This paper presents data
      regarding endothelial cell loss in aphakic and pseudophakic silicone oil filled
      eyes when oil was retained for many months. This study updates our previous
      investigation on the subject. PATIENTS AND METHODS: The corneal endothelial cell
      count of 10 eyes of 10 consecutive patients who had undergone vitreoretinal
      surgery, including fluid-gas exchange and ultimately silicone oil placement, were
      obtained. The patients underwent an average of 2.7+/-0.9 vitreoretinal procedures
      before the final procedure which induced the placement of silicone oil in the
      vitreous cavity. All had inferior iridectomies. The endothelial cell density
      measurements were obtained an average of 1 year after silicone oil placement. In
      all eyes, the oil was felt necessary for long term tamponade and therefore was
      not removed. The cell density of the operated eye was compared to the fellow eye,
      none of which had undergone silicone oil placement. RESULTS: Both gas and
      retained silicone oil contribute to the loss of corneal endothelial cell density.
      The average endothelial cell loss in the 10 eyes with oil retained for an average
      of 10+/-12 months was 68.8 +/-31.4%, as compared to the fellow eye. The average
      cell loss was higher in the three eyes with silicone oil in the anterior chamber
      (range 44 to >95%). Pseudophakic eyes fared better, on average, than aphakic eyes
      (51.66+/-28% vs. 66.63+/-26.3%) with respect to cell loss. Five aphakic eyes and
      1 pseudophakic eye developed corneal edema. CONCLUSIONS: Endothelial cell loss
      occurs after vitreoretinal surgery and is exacerbated by long term silicone oil
      retention. The corneal endothelial cell damage is probably cumulative from
      procedure to procedure. Endothelial cell loss may be pronounced in eyes without a
      physical barrier between the anterior segment and the vitreous cavity, and in
      eyes where oil migrates into anterior chamber.

PMID- 10929973
TI  - Treatment of macular disease with a binocular indirect ophthalmoscope laser
      delivery system.
AB  - BACKGROUND AND OBJECTIVE: Some patients with macular disease, because of physical
      infirmity or disability, cannot be treated with laser photocoagulation using a
      typical slit lamp delivery system. The purpose of this study was to determine
      whether the binocular indirect ophthalmoscope could be used to deliver treatment
      to the macula when photocoagulation would otherwise be very difficult, if not
      impossible, to perform. MATERIALS AND METHODS: Ten eyes of 10 patients who could
      not sit for slit lamp laser delivery were treated with binocular indirect
      ophthalmoscope laser photocoagulation over a 36 month period. Eight had subfoveal
      choroidal neovascularization (CNV) from age-related macular degeneration (AMD),
      and 2 patients had clinically significant macular edema (CSME) from diabetes
      mellitus. Argon laser photocoagulation was delivered to the choroidal neovascular
      membrane in patients with exudative AMD, and a grid treatment was given to eyes
      with diabetic macular edema. RESULTS: Six of 8 patients with exudative AMD were
      successfully treated with eradication of the CNV. Two required retreatment within
      6 months of original treatment. Both patients with CSME had resolution of their
      edema at 3 and 6 months after treatment. Best corrected visual acuity did not
      change by more than 2 Snellen lines in any patient with CNV and 1 Snellen line in
      patients with CSME. No complications of treatment were encountered. CONCLUSION:
      In certain circumstances, laser photocoagulation of the macula using the indirect
      ophthalmoscope laser delivery system should be considered when more conventional
      treatment strategies cannot be implemented.

PMID- 10929974
TI  - The role of axial length in central and branch retinal vein occlusion.
AB  - BACKGROUND AND OBJECTIVE: To assess whether the axial length is a local risk
      factor in central retinal vein occlusion (CRVO) and branch retinal vein occlusion
      (BRVO). PATIENTS AND METHODS: The axial lengths of affected and fellow eyes of 19
      patients with CRVO and 27 with BRVO and of their controls were measured with A
      scan ultrasonography. The control group consisted of 17 individuals for CRVO and
      25 for BRVO matched in age, sex and the prevalence of hypertension and diabetes
      in patient groups. The results of measurements in affected, unaffected and
      control eyes were compared. RESULTS: The mean axial length was different among
      the affected and unaffected eyes in patients with CRVO and their controls (P <
      .05). The affected eyes had significantly shorter axial length compared to the
      fellow and control eyes (P < .01 and P < .01, respectively). In the BRVO group,
      the mean axial length did not differ among affected, unaffected and control eyes
      (P > .05). CONCLUSIONS: Our study demonstrates a significantly shorter axial
      length in eyes with CRVO and not significantly shorter axial length in those with
      BRVO. The shorter axial length could be an additional risk factor in the
      pathogenesis of CRVO.

PMID- 10929976
TI  - Eyes removed for primary ulcerative keratitis with endophthalmitis: microbial and
      histologic findings.
AB  - OBJECTIVES: To study the microbiological and histological findings in patients
      whose eyes are removed for primary ulcerative keratitis with suppurative
      endophthalmitis. METHODS: Survey of consecutive cases of ulcerative keratitis
      with histologically defined endophthalmitis treated by enucleation or
      evisceration. RESULTS: Eighteen cases of ulcerative keratitis with suppurative
      endophthalmitis were identified. Thirteen corneal ulcers were culture positive
      (72%). Microorganism were found in histologic sections of the anterior segment of
      9 eyes (50%), but no microorganisms were identified in the vitreous. Two eyes
      (11%) had culture-positive endophthalmitis. Half of the patients in this study
      who had undergone elective intraocular surgery had done so within 4 months of
      enucleation. CONCLUSIONS: Considerable vitreous inflammation can occur with
      microbial keratitis in the absence of histologically demonstrable microorganisms
      in the vitreous. Microbial keratitis associated with suppurative endophthalmitis
      is usually caused by virulent organisms. The factors that contributed to the
      spread of purulent inflammation inside the eye could not be assessed in this
      morphologic study because of the lack of clinical data.

PMID- 10929977
TI  - Open drops in ophthalmology offices: expiration and contamination.
AB  - OBJECTIVE: To determine the relationship between eye drop use and contamination
      rate in ophthalmology offices. DESIGN: Following permission request, open bottles
      were examined and the nozzle tip and one drop of content was cultured on solid
      media. OUTCOME MEASURES: Drug category, volume, weight compared to full, clean
      legible label, expiration date; 2 or more bacterial colonies along the
      inoculation site. RESULTS: In 18 offices, of 1,485 open bottles (mean 12.2, range
      4 to 23 per lane) on average 19.8% (range 0% to 88%) were expired (16.2 of 82.5
      bottles per office). The frequency of occurrence (%) and expiration (%E) were
      40.3% cycloplegics (19.4%E); 16.4% glaucoma (33.7%E); 10.8% anesthetics (8.8%E);
      and 4% steroids (8.8%E; or 42.2%E including one outlier). Most likely expired
      were glaucoma (P < 0.001); small 2-3 ml (P < 0.02), nearly empty (P < 0.05), or
      dirty (P < 0.001) bottles. Only one (5 ml cyclopentolate, not expired) grew a
      Micrococcus (0.07%). CONCLUSIONS: Drops in ophthalmology offices may be expired
      but are not contaminated.

PMID- 10929978
TI  - Outcome of laser peripheral iridotomy in chronic primary angle closure glaucoma.
AB  - BACKGROUND AND OBJECTIVES: To report the effect of laser peripheral iridotomy on
      the angles of eyes with chronic angle closure glaucoma. PATIENTS AND METHODS: The
      hospital records of 171 consecutive patients with chronic primary angle closure
      glaucoma (CPACG) seen between October 1994 and March 1997 were analyzed to study
      the gonioscopic outcome of laser peripheral iridotomy (LPI). Success was defined
      as open angles (with or without medications for intraocular pressure (IOP)
      control) following LPI at the 1 month follow-up. RESULTS: Forty-seven eyes of 34
      patients had chronic appositional angle closure glaucoma (CAACG), and 186 eyes of
      124 patients had chronic synechial angle closure glaucoma (CSACG). Seventy eyes
      of 57 patients that underwent primary trabeculectomy for advanced disease were
      excluded from the study. Two hundred thirty-three eyes of 158 patients underwent
      LPI; the angles could be opened in 171 eyes (73.4%; confidence interval 67.7% to
      79.1%) of 117 patients. Medications to control the IOP were required in 25 eyes
      (10.7%) of 19 patients. Fifty-four eyes of 34 patients that did not respond to
      LPI underwent argon laser gonioplasty. Gonioplasty was successful in opening at
      least 180 degrees of the angle in all eyes. There was no significant difference
      in success between CAACG (74.5%) and CSACG (73.1%). Age, IOP, and field loss were
      not predictors of outcome. There was perfect concordance of results between the 2
      eyes of patients who had bilateral LPI. CONCLUSIONS: In this series, laser
      iridotomy was successful in opening the angle in 73.4% of eyes. Gonioplasty
      opened the angle in all eyes that underwent this procedure. The effect of
      iridotomy on one eye was predictive of the effect on the fellow eye.

PMID- 10929979
TI  - Polyglactin sutures versus nylon sutures for scleral flap suturing in
      trabeculectomy.
AB  - BACKGROUND AND OBJECTIVES: To note the effect on filtration function of using
      polyglactin sutures for scleral flap suturing in trabeculectomy. PATIENTS AND
      METHODS: Polyglactin sutures were compared with nylon sutures to secure the
      scleral flap of trabeculectomy in 30 consecutive eyes. Parameters studied were
      intraocular pressure, central anterior chamber depth, and bleb score in this
      randomized prospective study. RESULTS: Observations regarding intraocular
      pressure, central anterior chamber depth and bleb score in the early
      postoperative period were comparable in the 2 groups. The results at 12 months
      follow-up reveal a lower mean IOP (P < 0.05) and a higher mean bleb score (P <
      0.05) in the group with polyglactin sutures. Success rate (defined as IOP < 21 mm
      Hg) at 12 months was 100% with use of polyglactin sutures compared to 80% with
      nylon sutures. CONCLUSIONS: Polyglactin sutures can be used as an alternative to
      nylon sutures for scleral flap suturing in trabeculectomy, with the possible
      additional benefit of better long-term filtration function.

PMID- 10929980
TI  - Relative efficacy of the argon green, argon blue-green, and krypton red lasers
      for 10-0 nylon subconjunctival laser suture lysis.
AB  - BACKGROUND AND OBJECTIVE: To determine the optimal wavelength for subconjunctival
      laser suture lysis. MATERIALS AND METHODS: 130 black monofilament 10-0 nylon
      sutures were sewn subconjunctivally into the bare sclera of enucleated rabbit
      globes. The lowest energy levels facilitating laser suture lysis were determined
      for the argon green (514.5 NM), argon blue-green (488.0 NM, 514.5 NM), and
      krypton red (647.1 NM) wavelengths. In addition, absorption spectroscopy was
      performed on the suture material and conjunctiva using the Perkin Elmer W/VIS
      Lambda 2 spectrometer. RESULTS: Krypton red produced the fewest buttonhole
      defects, and it was also the most efficient energy source for suture lysis (P =
      0.0001) under nontenectomized conjunctiva. Absorbance spectra studies revealed
      peak absorbance at 628 NM for the 10-0 nylon suture material. CONCLUSIONS: Based
      on animal and absorption spectroscopy studies, krypton red may be a safer and
      more efficient wavelength for subconjunctival laser suture lysis.

PMID- 10929981
TI  - Necrotizing conjunctival ulceration following subconjunctival depot
      methylprednisolone injection.
AB  - To report the occurrence of a necrotizing conjunctival ulcer at the site of
      methylprednisolone injection. A 35-year-old woman underwent a routine
      extracapsular cataract extraction. Subconjunctival methylprednisolone acetate
      (Depo-Medrol, Pharmacia & Upjohn, Kalamazoo, MI) was injected at the end of the
      operation. A necrotizing conjunctival ulcer developed at the site of injection.
      Necrotic tissue and remnants of the drug were excised, and the conjunctiva healed
      within 10 days. Postoperative subconjunctival injection of methylprednisolone may
      cause necrosis and ulceration of the overlying conjunctiva. Subconjunctival and
      subtendon corticosteroid injections are commonly used in various inflammatory
      ocular conditions and prophylactically after intraocular operations. We describe
      a case of conjunctival necrosis at the site of injection, an adverse effect that
      has been previously reported in only 1 case in the ophthalmological literature.

PMID- 10929982
TI  - Late-onset unilateral primary developmental glaucoma associated with
      iridotrabecular dysgenesis, congenital ectropion uveae and thickened corneal
      nerves: a new neural crest syndrome?
AB  - The association of unilateral primary developmental glaucoma with iridotrabecular
      dysgenesis and congenital ectropion uveae has been well documented in the
      literature. The glaucoma in this entity may present at birth, infancy or may
      develop at a later stage in life. I report the case of a child with late-onset
      unilateral primary developmental glaucoma due to iridotrabecular dysgenesis,
      congenital ectropion uveae, and who had a previously undescribed association with
      ipsilateral thickened corneal nerves in the stroma.

PMID- 10929983
TI  - The use of scleral transillumination to localized the extent of a cyclodialysis
      cleft.
AB  - Several techniques have been described to localize and repair cyclodialysis
      clefts. We describe a technique that may be used to easily and accurately
      localize a cyclodialysis cleft using scleral transillumination. We have verified
      the accuracy of this technique using high frequency ultrasound biomicroscopy. The
      location of the cleft was verified using high frequency ultrasound biomicroscopy.
      Scleral transillumination may facilitate the accurate location of cyclodialysis
      and may be a useful adjunct in planning the surgical repair of a cyclodialysis
      cleft.

PMID- 10929984
TI  - Explantation of silicone plate haptic intraocular lenses.
AB  - The stress on small self-sealing incisions in cataract surgery has resulted in
      the increased use of foldable intraocular lenses (IOL). Plate haptic silicone
      IOLs implanted with the help of an injector require extremely small incision
      lengths and are extensively used. The authors discuss difficulties in explanting
      such lenses, especially in inflamed eyes. Two patients who underwent plate-haptic
      silicone IOL explantation for postoperative bacterial endophthalmitis are
      described. Plate haptic IOLs have a tendency to dislocate posteriorly because of
      poor capsular fixation and increased posterior bowing. Enlarging a small rhexis
      prior to attempting explantation of these lenses reduces this complication.
      Difficulties inherent in explanting plate haptic silicone IOLs in inflamed eyes
      are discussed, along with suggestions to overcome them.

PMID- 10929985
TI  - Orbital leiomyosarcoma after retinoblastoma.
AB  - Patients with the inherited, bilateral form of retinoblastoma have an increased
      incidence of osteogenic sarcoma such that the mortality from the secondary tumor
      exceeds that of the initial bilateral retinoblastoma. We report a 29-year-old
      male survivor of bilateral retinoblastomas originally diagnosed at 8 months of
      age, whose treatment eventually included bilateral enucleation, bilateral orbital
      radiation, and systemic chemotherapy. At age 26, a tumor removed from his right
      maxillary sinus was diagnosed as fibroma. At age 29, he developed an inferior
      orbital mass that extended into the right maxillary sinus. A biopsy and
      comparison with the previous maxillary sinus mass revealed both lesions to be
      leiomyosarcoma. Both light and electron microscopy supported the diagnosis. The
      patient has survived treatment with orbital exenteration and maxillectomy
      combined with postoperative radiation to the right orbital-maxillary area. This
      appears to be the fourth case of leiomyosarcoma in the third decade of life in a
      male patient with a previously irradiated orbit after enucleation for bilateral
      retinoblastoma. Leiomyosarcoma appears to be another orbital tumor associated
      with bilateral retinoblastoma.

PMID- 10929986
TI  - Pyogenic granuloma: a rare complication of silicone punctal plugs.
AB  - To describe pyogenic granuloma formation associated with silicone punctal plugs.
      A 65-year-old woman with severe dry eye was treated with silicone punctal plugs
      in both upper and lower puncta. After 14 months of success with the plugs, the
      patient presented with a fleshy ampullary lesion overlying the plugged superior
      punctum of her right eye. It was clinically diagnosed as a pyogenic granuloma,
      and the silicone plug was removed. Since the lesion persisted for 1 month, it was
      surgically removed. Histopathologic examination confirmed the diagnosis of
      pyogenic granuloma. A new plug was inserted and tolerated well. The routine use
      of silicone plugs are recommended as long as patients are informed of possible
      rare complications.

PMID- 10929987
TI  - Reusable superelastic iris retractor. The Microsurgery Advanced Design
      Laboratory.
AB  - We report the development and testing of a new reusable iris retractor for
      surgical dilatation of the pupil. The iris retractor is composed of superelastic
      nitinol (nickel-titanium alloy) which can be repeatedly flexed. The reusable
      superelastic iris retractor is a valuable new device for temporary mechanical
      dilation of the pupil. Its mechanical properties have proven its effectiveness as
      a reliable device for repeated clinical use.

PMID- 10929988
TI  - A new technique for separation of posterior vitreous in vitreous surgery.
AB  - To describe a new and effective technique, hydroseparation, for use in detaching
      the posterior cortical vitreous from the retina by the simple injection of fluid
      into the subhyaloid space. This technique was used in 7 eyes of 6 patients with
      diabetic retinopathy who had limited posterior vitreous detachment. Following
      core vitrectomy, a 32 gauge cannula was inserted into the subhyaloid space and a
      balanced salt solution (BSS) was injected. The injected fluid spread easily to
      the periphery, causing the vitreous cortex to be smoothly separated, except for
      areas with firm vitreoretinal adhesion. In those areas, we also used
      microscissors to separate the tissue. No iatrogenic retinal break occurred in any
      case. This simple technique, which exerts minimal traction force on the retina,
      was safe and useful for inducing posterior vitreous detachment in patients with
      diabetes.

PMID- 10929989
TI  - In-hospital complication occurrence as a screen for quality-of-care problems:
      what's next?

PMID- 10929990
TI  - Update from funders: The Robert Wood Johnson Foundation.

PMID- 10929991
TI  - Identification of in-hospital complications from claims data. Is it valid?
AB  - OBJECTIVES: This study examined the validity of the Complications Screening
      Program (CSP) by testing whether (1) ICD-9-CM codes used to identify a
      complication are coded completely and accurately and (2) the CSP algorithm
      successfully separates conditions present on admission from those occurring in
      the hospital. METHODS: We compared diagnosis and procedure codes contained in the
      Medicare claim with codes abstracted from an independent re-review of more than
      1,200 medical records from Connecticut and California. RESULTS: Eighty-nine
      percent of the surgical cases and 84% of the medical cases had their CSP trigger
      codes corroborated by re-review of the medical record. For 13% of the surgical
      cases and 58% of the medical cases, the condition represented by the code was
      judged to be present on admission rather than occurring in-hospital. The positive
      predictive value of the claim was greater than 80% for the surgical risk pool,
      suggesting the value of the CSP as a screening tool. CONCLUSIONS: The CSP has
      validity as a screen for most surgical complications but only for 1 medical
      complication. The CSP does not have validity as a "stand-alone" tool to identify
      more than a few in-hospital surgery-related events. The addition of an indicator
      to the Medicare claim to capture the timing of secondary diagnoses would improve
      the validity of the CSP for identifying both surgical and medical in-hospital
      events.

PMID- 10929993
TI  - Impact of relational coordination on quality of care, postoperative pain and
      functioning, and length of stay: a nine-hospital study of surgical patients.
AB  - BACKGROUND: Health care organizations face pressures from patients to improve the
      quality of care and clinical outcomes, as well as pressures from managed care to
      do so more efficiently. Coordination, the management of task interdependencies,
      is one way that health care organizations have attempted to meet these
      conflicting demands. OBJECTIVES: The objectives of this study were to introduce
      the concept of relational coordination and to determine its impact on the quality
      of care, postoperative pain and functioning, and the length of stay for patients
      undergoing an elective surgical procedure. Relational coordination comprises
      frequent, timely, accurate communication, as well as problem-solving, shared
      goals, shared knowledge, and mutual respect among health care providers. RESEARCH
      DESIGN: Relational coordination was measured by a cross-sectional questionnaire
      of health care providers. Quality of care was measured by a cross-sectional
      postoperative questionnaire of total hip and knee arthroplasty patients. On the
      same questionnaire, postoperative pain and functioning were measured by the WOMAC
      osteoarthritis instrument. Length of stay was measured from individual patient
      hospital records. SUBJECTS: The subjects for this study were 338 care providers
      and 878 patients who completed questionnaires from 9 hospitals in Boston, MA, New
      York, NY, and Dallas, TX, between July and December 1997. MEASURES: Quality of
      care, postoperative pain and functioning, and length of acute hospital stay.
      RESULTS: Relational coordination varied significantly between sites, ranging from
      3.86 to 4.22 (P <0.001). Quality of care was significantly improved by relational
      coordination (P <0.001) and each of its dimensions. Postoperative pain was
      significantly reduced by relational coordination (P = 0.041), whereas
      postoperative functioning was significantly improved by several dimensions of
      relational coordination, including the frequency of communication (P = 0.044),
      the strength of shared goals (P = 0.035), and the degree of mutual respect (P =
      0.030) among care providers. Length of stay was significantly shortened (53.77%,
      P <0.001) by relational coordination and each of its dimensions. CONCLUSIONS:
      Relational coordination across health care providers is associated with improved
      quality of care, reduced postoperative pain, and decreased lengths of hospital
      stay for patients undergoing total joint arthroplasty. These findings support the
      design of formal practices to strengthen communication and relationships among
      key caregivers on surgical units.

PMID- 10929992
TI  - Use of administrative data to find substandard care: validation of the
      complications screening program.
AB  - OBJECTIVE: The use of administrative data to identify inpatient complications is
      technically feasible and inexpensive but unproven as a quality measure. Our
      objective was to validate whether a screening method that uses data from standard
      hospital discharge abstracts identifies complications of care and potential
      quality problems. DESIGN: This was a case-control study with structured implicit
      physician reviews. SETTING: Acute-care hospitals in California and Connecticut in
      1994. PATIENTS: The study included 1,025 Medicare beneficiaries greater than 265
      years of age. METHODS: Using administrative data, we stratified acute-care
      hospitals by observed-to-expected complication rates and randomly selected
      hospitals within each state. We randomly selected cases flagged with 1 of 17
      surgical complications and 6 medical complications. We randomly selected controls
      from unflagged cases. MAIN OUTCOME MEASURE: Peer-review organization physicians'
      judgments about the presence of the flagged complication and potential quality-of
      care problems. RESULTS: Physicians confirmed flagged complications in 68.4% of
      surgical and 27.2% of medical cases. They identified potential quality problems
      in 29.5% of flagged surgical and 15.7% of medical cases but in only 2.1% of
      surgical and medical controls. The rate of physician-identified potential quality
      problems among flagged cases exceeded 25% in 9 surgical screens and 1 medical
      screen. Reviewers noted several potentially mitigating circumstances that
      affected their judgments about quality, including factors related to the
      patients' illness, the complexity of the case, and technical difficulties that
      clinicians encountered. CONCLUSIONS: For some types of complications, screening
      administrative data may offer an efficient approach for identifying potentially
      problematic cases for physician review. Understanding the basis for physicians'
      judgments about quality requires more investigation.

PMID- 10929994
TI  - Prediction rules for complications in coronary bypass surgery: a comparison and
      methodological critique.
AB  - BACKGROUND: Clinical prediction rules have been developed that use preoperative
      information to stratify patients according to risk of complications after cardiac
      surgery. OBJECTIVES: To assess the methodological standards and performance of 7
      models. PARTICIPANTS: The validation portion of the Quality Measurement and
      Management Initiative (QMMI) cohort included a random sample of all adult
      patients (n = 3,261) who underwent coronary artery bypass grafting (CABG) surgery
      not involving valvular or other concomitant procedures at 12 medical centers from
      August 1993 to October 1995. OUTCOME MEASURES: Methodological standards used for
      model comparison were adapted from published criteria. Model performance was
      assessed by receiver-operating characteristic (ROC) analysis, and calibration was
      evaluated with the Hosmer-Lemeshow (HL) statistic and observed-expected plots.
      METHODS: We performed cross-validation by applying the published criteria for the
      development of each model to the validation subset of the QMMI cohort and by
      assessing the performance of each model in discriminating outcomes. RESULTS: Wide
      variations existed in the methodologies used to develop and validate the 5
      additive scores evaluated. Cross-validation of all 5 additive scores revealed
      degradation in their abilities to discriminate outcomes. The 2 logistic models
      examined performed similarly to the additive scores examined in predicting
      mortality. CONCLUSIONS: Substantial variation existed both in the methodologies
      used to develop models and in the ability of the models to predict outcomes.
      Models developed at single institutions or using fewer patients may be less
      generalizable when applied to diverse clinical settings. Additive and logistic
      regression models performed similarly, as assessed by ROC and HL analyses.

PMID- 10929995
TI  - Physician referral rates: style without much substance?
AB  - BACKGROUND: Primary care physicians (PCPs) exhibit widely varying referral rates,
      resulting in dramatic differences in the exposure of their patients to
      specialists. The relationships between this physician behavior and costs and
      patient outcomes are unknown. OBJECTIVES: To examine the relationships between
      PCP referral rates and costs, risk of avoidable hospitalization, health status,
      and satisfaction. DESIGN: Cross-sectional analyses of claims and patient survey
      data. SETTING AND SUBJECTS: Independent practice association (IPA)-style managed
      care organization in the Rochester, NY, metropolitan area. The 1995 claims data
      included 457 PCPs in the IPA and 217,606 adult patients assigned to their panels.
      Approximately 50 consecutive patients of each of a random sample of 100 PCPs
      completed a patient survey in 1997-1998. MEASURES: From the claims data, total
      expenditures per panel member, the risk of avoidable hospitalization, and
      physician referral rate were measured. Measures derived from the survey included
      SF-12 scores, satisfaction, and physician referral rate. RESULTS: The
      relationship between physician referral rate and per-panel-member costs was not
      statistically significant after case-mix adjustment of the referral rate. There
      was no relationship between the case-mix-adjusted referral rate and risk of
      avoidable hospitalization. In the survey data, there was no adjusted relationship
      between the physicians' referral rate and their patients' self-rated physical or
      mental health. There was a modest direct relationship between patient
      satisfaction and survey-derived referral rate. CONCLUSIONS: Despite stable, wide
      variations in PCP referral rates, there are few discemible relationships between
      this physician behavior and costs and patient outcomes. Efforts to constrain PCP
      referrals to specialists may be misguided.

PMID- 10929996
TI  - Validation study of retrospective recall of disease-targeted function: results
      from the prostate cancer outcomes study.
AB  - OBJECTIVES: This was an ancillary methodological study within the Prostate Cancer
      Outcomes Study (PCOS) to assess the validity of 6-month retrospective recall of
      prediagnostic disease-targeted function among men diagnosed with prostate cancer.
      METHODS: A convenience sample of 133 prostate cancer cases were administered a
      baseline questionnaire shortly after diagnosis that asked about prediagnostic
      urinary, sexual, and bowel function. They were surveyed again concerning the same
      items 6 months later and asked to recall their prediagnostic function. Reports of
      prediagnostic function obtained at baseline and 6 months are compared, as are
      measures of change derived from these reports. Percent agreement and weighted
      kappas are calculated to measure the extent of agreement. RESULTS: Over 70% of
      the men reported prediagnostic functioning at the highest level on 12 of 17
      survey items. For each of these items, recall at 6 months was identical to the
      baseline survey response for > or =69% of the men. The values of the weighted
      kappas for changes computed with baseline reports (prospective) and changes
      computed with 6-month recall (retrospective) ranged from 0.396 to 0.919 for the
      17 individual items. Intraclass correlations for the retrospective versus
      prospective changes in the multi-item function scores were 0.828 for urinary,
      0.618 for bowel, and 0.692 for sexual function. CONCLUSIONS: At baseline, men
      recently diagnosed with prostate cancer report few disease-related problems
      before diagnosis, and a high percentage of men recall this accurately 6 months
      later. There is reasonably high agreement between baseline and 6-month estimates
      of prediagnostic function and between prospective and retrospective measures of
      change over 6 months.

PMID- 10929997
TI  - Negative affectivity and health-related quality of life.
AB  - OBJECTIVES: Although personality is known to influence patients' self-ratings of
      health, its effects on reports of health-related quality of life (HRQOL) have not
      been fully described. We examined the relationship between a dimension of
      personality called negative affectivity (NA; a general disposition to experience
      negative mood states) and HRQOL, controlling for age and common chronic physical
      and mental diseases. METHODS: We used data from 3 samples of veterans: the
      Department of Veterans Affairs (VA) Normative Aging Study (NAS), the Veterans
      Health Study (VHS), and the VA Women's Health Project (VA WHP). For each of the 8
      SF-36 scales and the physical and mental component summary scales, 2 regression
      models were estimated, the first of which included only chronic diseases and age
      and the second of which added NA. RESULTS: NA was consistently negatively
      associated with SF-36 scale scores in bivariate analyses. The regression models
      indicated that across the 3 samples, NA explained between 0% and 13.9% additional
      variance in the scales, with the least additional variance in the physical
      function domains (range 0-2.6%) and the most in the mental function domains
      (range 0-13.9%). Results from the summary scales were similar: NA explained none
      of the variance in the physical component summary and 3.5% to 10.4% in the mental
      component summary. These results were largely consistent across the 3 samples.
      CONCLUSIONS: These results suggest the importance of NA in patients' ratings of
      HRQOL beyond that of age and chronic conditions. Thus, clinicians and researchers
      who rely on measures such as the SF-36 to assess health status should consider
      that personality, as well as underlying health, can affect self-ratings of HRQOL.

PMID- 10929998
TI  - Does clinical evidence support ICD-9-CM diagnosis coding of complications?
AB  - BACKGROUND: Hospital discharge diagnoses, coded by use of the International
      Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM),
      increasingly determine reimbursement and support quality monitoring. Prior
      studies of coding validity have investigated whether coding guidelines were met,
      not whether the clinical condition was actually present. OBJECTIVE: To determine
      whether clinical evidence in medical records confirms selected ICD-9-CM discharge
      diagnoses coded by hospitals. RESEARCH DESIGN AND SUBJECTS: Retrospective record
      review of 485 randomly sampled 1994 hospitalizations of elderly Medicare
      beneficiaries in Califomia and Connecticut. MAIN OUTCOME MEASURE: Proportion of
      patients with specified ICD-9-CM codes representing potential complications who
      had clinical evidence confirming the coded condition. RESULTS: Clinical evidence
      supported most postoperative acute myocardial infarction diagnoses, but fewer
      than 60% of other diagnoses had confirmatory clinical evidence by explicit
      clinical criteria; 30% of medical and 19% of surgical patients lacked objective
      confirmatory evidence in the medical record. Across 11 surgical and 2 medical
      complications, objective clinical criteria or physicians' notes supported the
      coded diagnosis in >90% of patients for 2 complications, 80% to 90% of patients
      for 4 complications, 70% to <80% of patients for 5 complications, and <70% for 2
      complications. For some complications (postoperative pneumonia, aspiration
      pneumonia, and hemorrhage or hematoma), a large fraction of patients had only a
      physician's note reporting the complication. CONCLUSIONS: Our findings raise
      questions about whether the clinical conditions represented by ICD-9-CM codes
      used by the Complications Screening Program were in fact always present. These
      findings highlight concerns about the clinical validity of using ICD-9-CM codes
      for quality monitoring.

PMID- 10929999
TI  - Provision of feedback on perceived health status to health care professionals.

PMID- 10930000
TI  - Intentional body clipping of wide-necked basilar artery bifurcation aneurysms.
AB  - OBJECT: Neck clipping or coil embolization cannot always achieve complete neck
      obstruction in wide-necked basilar artery (BA) bifurcation aneurysms. Clipping of
      the aneurysm body, leaving a small aneurysm rest, is one clipping method used for
      this kind of aneurysm to maintain the patency of the posterior cerebral arteries
      and perforating vessels. However, the long-term efficacy of intentional body
      clipping has not been well investigated. The authors reviewed their experience
      with intentional body clipping of wide-necked BA bifurcation aneurysms to
      determine suitable clipping techniques and the long-term efficacy of the
      procedure. METHODS: Complete neck occlusion was abandoned and body clipping
      intentionally performed in 17 patients with BA bifurcation aneurysms; wrapping of
      the aneurysm rest was made in seven cases. There were 10 ruptured aneurysms
      (58.8%), and the size of the aneurysm was larger than 10 mm in 11 patients
      (64.7%). The width between the clip blades and the base of the aneurysm neck was
      1 mm in 11 cases, 2 mm in four, and 3 mm in two. Favorable outcome (Glasgow
      Outcome Scale [GOS] Score 4 or 5) was obtained in 13 cases (76.5%) and
      unfavorable outcome (GOS Scores 1-3) in four cases (23.5%). Major causes of
      unfavorable outcome included injury to perforating arteries and major vessel
      occlusion following surgical manipulation, in addition to the primary damage
      caused by subarachnoid hemorrhage. Subarachnoid hemorrhage did not occur during a
      mean follow-up period of 7.4+/-5.6 years (range 0.7-18.1 years) after treatment.
      CONCLUSIONS: Intentional body clipping of wide-necked BA aneurysms proved to be
      effective to prevent subarachnoid hemorrhage, although injury to perforating
      arteries remains problematic. The choice of complete neck clipping or body
      clipping should be established early during the microsurgical procedure to reduce
      the risk of injury to perforating vessels.

PMID- 10930001
TI  - Prospective analysis of aneurysm treatment in a series of 103 consecutive
      patients when endovascular embolization is considered the first option.
AB  - OBJECT: The aim of this study was to evaluate prospectively the results of
      treating cerebral aneurysms with coil embolization (CE) or with surgical clipping
      when CE was considered the first option. METHODS: Whenever an aneurysm was to be
      treated, CE was first considered by our neurovascular team. Surgical clipping was
      reserved for cases excluded from CE or cases in which CE failed. The study
      consisted of 103 consecutive patients with 132 aneurysms, of which 127 were
      treated. Coil embolization was performed using Guglielmi detachable coils, and
      surgery was performed using Zeppelin clips. Three groups were defined: Group A
      consisted of 64 aneurysms that were treated by CE (neck/sac ratio < 1:3); Group
      B, 63 aneurysms that were surgically clipped; and Group C, 12 aneurysms that
      failed to be satisfactorily (> or = 95%) embolized and were subsequently clipped.
      The percentages of residual aneurysm were 31.2% in Group A, 1.6% in Group B, and
      0% in Group C. The percentages of patients with poor Glasgow Outcome Scale (GOS)
      scores (GOS Scores 1-3) were 13.3% in Group A, 6.1% in Group B, and 8.3% in Group
      C. The percentages of poor outcome (GOS Scores 1-3) in patients with good
      clinical status before treatment were 10.7% in Group A, 0% in Group B, and 8.3%
      in Group C. CONCLUSIONS: Even with preselection, CE remains associated with a
      significant number of treatment failures and poor outcomes, even in patients with
      good preoperative clinical status. Surgical clipping can offer better results
      than CE, even for more complex aneurysms of the anterior circulation, especially
      for those involving the middle cerebral artery cases. However, because CE can be
      effective and causes less stress and invasiveness for the patient, it should be
      considered first in aneurysms strictly selected by a neurovascular team.

PMID- 10930002
TI  - Contribution of edema and cerebral blood volume to traumatic brain swelling in
      head-injured patients.
AB  - OBJECT: The pathogenesis of traumatic brain swelling remains unclear. The
      generally held view is that brain swelling is caused primarily by vascular
      engorgement and that edema plays a relatively minor role in the swelling process.
      The goal of this study was to examine the roles of cerebral blood volume (CBV)
      and edema in traumatic brain swelling. METHODS: Both brain-tissue water and CBV
      were measured in 76 head-injured patients, and the relative contribution of edema
      and blood to total brain swelling was determined. Comparable measures of brain
      tissue water were obtained in 30 healthy volunteers and CBV in seven volunteers.
      Brain edema was measured using magnetic resonance imaging, implementing a new
      technique for accurate measurement of total tissue water. Measurements of CBV in
      a subgroup of 31 head-injured patients were based on consecutive measures of
      cerebral blood flow (CBF) obtained using stable xenon and calculation of mean
      transit time by dynamic computerized tomography scanning after a rapid bolus
      injection of iodinated contrast material. The mean (+/- standard deviation)
      percentage of swelling due to water was 9.37+/-8.7%, whereas that due to blood
      was -0.8+/-1.32%. CONCLUSIONS: The results of this study showed that brain edema
      is the major fluid component contributing to traumatic brain swelling. Moreover,
      CBV is reduced in proportion to CBF reduction following severe brain injury.

PMID- 10930003
TI  - Long-term surgical outcome in 16 patients with thyrotropin pituitary adenoma.
AB  - OBJECT: Thyrotropin-secreting pituitary adenomas are rare lesions of the
      endocrinological system. Although introduction of a hypersensitive
      radioimmunoassay for thyrotropin enables the recognition of inappropriate
      secretion of this hormone, the aforementioned lesions remain uncommon and
      unfamiliar to most neurosurgeons. It has been reported previously that surgical
      cure of thyrotropin-secreting adenomas is more difficult than in other functional
      adenomas because of the large size and invasive features of the former. However,
      the long-term outcome after surgery has not been well documented. The authors
      report on a surgical series of 16 patients with thyrotropin adenoma and the
      results of long-term follow up. METHODS: Sixteen patients ages 23 to 62 years (12
      women and four men) underwent transsphenoidal removal of thyrotropin adenomas
      between 1983 and 1999. These patients had the syndrome of inappropriate
      thyrotropin secretion (SITS) with pituitary mass lesions. Four of the patients
      had undergone previous subtotal thyroidectomy and/or radioiodine thyroid
      ablation, and 11 had been treated with antithyroid medication. Radiological
      investigations demonstrated macroadenomas in 14 patients, and 10 of those had
      cavernous sinus invasion. Surgical findings showed unusually fibrous and firm
      tumors in 13 (81.2%) of 16 patients. Preoperative octreotide administration was
      revealed to be effective for serum thyrotropin reduction as well as tumor
      shrinkage. Transsphenoidal surgery was performed with no morbidity resulting.
      Surgical remission was achieved in 10 (62.5%) of 16 patients, and total remission
      was achieved in 14 patients (87.5%) with a combination of additional radiation or
      medical therapy. In the other two patients, SITS persisted because of tumor rests
      in the cavernous sinus. Therefore, radiation and/or antithyroid therapy was
      administered. In the mean follow-up period of 7.5 years (range 11 months-15.8
      years), no recurrence of tumor was observed on magnetic resonance images, whereas
      recurrence of SITS was found in two patients with no tumor regrowth. In addition,
      coexistent primary hyperthyroidism was found in two other patients despite
      remission of SITS after surgery. CONCLUSIONS: Transsphenoidal surgery can achieve
      a good long-term outcome in patients with thyrotropin-secreting pituitary
      adenomas if surgery is performed before these become larger, invasive tumors. In
      the authors' experience, thyrotropin-secreting adenomas are fibrous and firm,
      which makes it difficult to achieve surgical remission. In addition, even
      satisfactory resection of the tumor sometimes results in recurrence of SITS or
      hyperthyroid symptoms due to coexistent primary hyperthyroidism. It is emphasized
      that a careful follow-up review is necessary after surgery, especially in
      patients with a long preoperative history of hyperthyroidism.

PMID- 10930004
TI  - Efficacy of neuroradiological imaging, neurological examination, and symptom
      status in follow-up assessment of patients with high-grade gliomas.
AB  - OBJECT: It is standard practice for the oncological follow-up of patients with
      brain tumors (especially in the setting of clinical trials) to include
      neurological examination and neuroradiological studies such as computerized
      tomography (CT) or magnetic resonance (MR) imaging in addition to evaluation of
      the patients' symptomatology and performance score. The validity of this practice
      and its impact on the welfare of patients with high-grade gliomas has not been
      adequately assessed. The purpose of this study is to provide such an assessment.
      METHODS: The authors studied 231 similarly treated patients who were
      participating in three prospective North Central Cancer Treatment Group or Mayo
      Clinic trials who developed progressive disease during follow up. According to
      the protocol, the symptom status, performance score, results of neurological
      examination, and CT or MR status were recorded prospectively in each patient at
      each evaluation (every 6-8 weeks). At progression, 177 (77%) of 231 patients
      experienced worsening of their baseline symptoms or they developed new ones. In
      the remaining 54 asymptomatic patients (23%), neuroradiological imaging revealed
      the progression. Asymptomatic progression was more likely to be detected on MR
      imaging compared with CT studies (p < 0.01). In no asymptomatic patient was
      progression detected on neurological examination alone. The median survival time
      after tumor recurrence was 13.3 weeks in symptomatic patients compared with 41.7
      weeks in the asymptomatic group (p < 0.0001). Asymptomatic patients were more
      aggressively treated, with surgery (p < 0.0001) and second-line chemotherapy (p <
      0.0002). Multivariate analysis of survival time following first progression by
      using both classification and regression trees and Cox models showed that
      treatment at recurrence was the most important prognostic variable. CONCLUSIONS:
      Symptoms are the most frequent indicators of progression in patients with high
      grade gliomas (77%). All asymptomatic progressions were detected on
      neuroradiological studies; MR imaging was more likely than CT scanning to reveal
      asymptomatic recurrences. Survival after disease progression was significantly
      longer in asymptomatic patients and could be related both to treatment following
      progression and to other favorable prognostic factors such as performance score.

PMID- 10930005
TI  - Computer-assisted neurosurgery by using a noninvasive vacuum-affixed dental cast
      that acts as a reference base: another step toward a unified approach in the
      treatment of brain tumors.
AB  - OBJECT: The purpose of the study was to evaluate the use of the Vogele-Bale
      Hohner (VBH) mouthpiece, which is attached to the patient's upper jaw by negative
      pressure, for patient-image registration and for tracking the patient's head
      during image-guided neurosurgery. METHODS: A dynamic reference frame (DRF) is
      reproducibly mounted on the mouthpiece. Reference points, optimally distributed
      and attached to the mouthpiece, are used for registration in the patient's
      absence on the day before surgery. In the operating room, the mouthpiece and DRF
      are precisely repositioned using a vacuum, and the patient's anatomical
      structures are automatically registered to corresponding ones on the image.
      Experimental studies and clinical experiences in 10 patients confirmed repeated
      (rigid body) localization accuracy in the range of 0 to 2 mm, throughout the
      entire surgery despite movements by the patient. CONCLUSIONS: Because of its
      noninvasive, rigid, reliable, and reproducible connection to the patient's head,
      the VBH vacuum-affixed mouthpiece grants the registration device an accuracy
      comparable to invasive fiducial markers.

PMID- 10930006
TI  - Sources of error in comparing functional magnetic resonance imaging and invasive
      electrophysiological recordings.
AB  - OBJECT: Several authors have recently reported studies in which they aim to
      validate functional magnetic resonance (fMR) imaging against the accepted gold
      standard of invasive electrophysiological monitoring. The authors have conducted
      a similar study, and in this paper they identify and quantify two characteristics
      of these data that can make such a comparison problematic. METHODS: Eight
      patients in whom surgery for epilepsy was performed and five healthy volunteers
      underwent fMR imaging to localize the part of the sensorimotor cortex responsible
      for hand movement. In the patient group subdural electrode mats were subsequently
      implanted to identify eloquent regions of the brain and the epileptogenic zone.
      The fMR imaging data were processed to correct for motion during the study and
      then registered with a postimplantation computerized tomography (CT) scan on
      which the electrodes were visible. The motion during imaging in the two groups
      studied, and the deformation of the brain between the preoperative images and
      postoperative scans were measured. The patients who underwent epilepsy surgery
      moved significantly more during fMR imaging experiments than healthy volunteers
      performing the same motor task. This motion had a particularly increased out-of
      plane component and was significantly more correlated with the stimulus than in
      the volunteers. This motion was especially increased when the patients were
      performing a task on the side affected by the lesion. The additional motion is
      hard to correct and substantially degrades the quality of the resulting fMR
      images, making it a much less reliable technique for use in these patients than
      in others. Also, the authors found that after electrode implantation, the brain
      surface can shift more than 10 mm relative to the skull compared with its
      preoperative location, substantially degrading the accuracy of the comparison of
      electrophysiological measurements made in the deformed brain and fMR studies
      obtained preoperatively. CONCLUSIONS: These two findings indicate that studies of
      this sort are currently of limited use for validating fMR imaging and should be
      interpreted with care. Additional image analysis research is necessary to solve
      the problems caused by patients' motion and brain deformation.

PMID- 10930007
TI  - Headaches in patients with radiosurgically treated occipital arteriovenous
      malformations.
AB  - OBJECT: The goal of this study was to determine the prevalence, characteristics,
      and radiosurgical outcomes of headaches associated with occipital arteriovenous
      malformations (AVMs). METHODS: The authors reviewed the medical records of 37
      consecutive patients with occipital AVMs who had been treated by radiosurgery to
      identify the radiological features of the AVMs before and after treatment and the
      clinical features and outcomes of headaches described in accordance with the
      criteria of the International Headache Society (IHS). Thirty-six patients (97.3%)
      were followed for a mean period of 46.6 months. The median volume of the AVMs was
      1.9 cm3, to which a mean radiation dose of 21.6 Gy was delivered. In the entire
      study group, periodic headaches were found in 17 patients (45.9%), of whom seven
      (18.9%) suffered from migraines with the characteristic visual aura. Migraine was
      predominantly found in patients with right-sided (p = 0.038) or laterally located
      (p = 0.025) AVMs. Factors associated with a higher incidence of any type of
      headache included larger nidus volume (p = 0.02), tortuous change of feeding
      artery (p = 0.036), and cortical drainage with reflux in the superior sagittal
      sinus (p = 0.032). The actuarial rate of angiographic obliteration was 71.6% at 3
      years. Headaches resolved or improved in 12 (70.6%) of 17 patients, including six
      (85.7%) of seven with migraine. The outcome of headache closely correlated with
      the obliteration results of the AVM (p = 0.002). CONCLUSIONS: A portion of
      occipital AVMs do cause headaches that satisfy the current IHS criteria for
      migraine, and the prevalence varies by the topography of the lesion. Radiosurgery
      can resolve headaches in the majority of treated patients.

PMID- 10930008
TI  - Gamma surgery for vein of Galen malformations.
AB  - OBJECT: The goal of this study was to evaluate the results of gamma surgery in
      nine patients treated for vein of Galen malformations (VGMs). METHODS: A
      consecutive series of nine VGMs in eight children aged 4 to 14 years and in one
      adult were treated with gamma surgery. Six of the patients were male, including
      the adult, and three were female. Among these patients there were three Yasargil
      Type I, one Type II, two Type III, and three Type IV malformations. Previous
      embolization had failed in four cases. Three VGMs were treated with gamma surgery
      twice. An additional patient with a Type III VGM underwent stereotactic
      angiography in preparation for gamma surgery but was judged to be suitable for
      direct embolization. Follow-up angiograms were obtained in eight of the VGMs
      treated. Four no longer filled; one has probably been obliterated, but this
      cannot be confirmed because the patient refused to undergo final angiography; one
      patient has residual fistulas not included in the initial treatment field, which
      were retreated recently; and two other patients have marked reduction of flow
      through their VGMs. CONCLUSIONS: Gamma surgery is a viable option in the
      treatment of VGMs in clinically stable patients. Combined endovascular therapy
      and gamma surgery is of benefit in complex malformations.

PMID- 10930009
TI  - Analysis of aqueductal cerebrospinal fluid flow after endoscopic aqueductoplasty
      by using cine phase-contrast magnetic resonance imaging.
AB  - OBJECT: The purpose of this prospective study was to evaluate aqueductal
      cerebrospinal fluid (CSF) flow after endoscopic aqueductoplasty. In all patients,
      preoperative magnetic resonance (MR) imaging revealed hydrocephalus caused by
      aqueductal stenosis and lack of aqueductal CSF flow. METHODS: In 14 healthy
      volunteers and in eight patients with aqueductal stenosis who had undergone
      endoscopic aqueductoplasty, aqueductal CSF flow was investigated using cine
      cardiac-gated phase-contrast MR imaging. For qualitative evaluation of CSF flow,
      the authors used an in-plane phase-contrast sequence in the midsagittal plane.
      The MR images were displayed in a closed-loop cine format. Quantitative through
      plane measurements were performed in the axial plane perpendicular to the
      aqueduct. Evaluation revealed no significant difference in aqueductal CSF flow
      between healthy volunteers and patients with regard to temporal parameters, CSF
      peak and mean velocities, mean flow, and stroke volume. All restored aqueducts
      have remained patent 7 to 31 months after surgery. CONCLUSIONS: Aqueductal CSF
      flow after endoscopic aqueductoplasty is similar to aqueductal CSF flow in
      healthy volunteers. The data indicate that endoscopic aqueductoplasty seems to
      restore physiological aqueductal CSF flow.

PMID- 10930010
TI  - Efficacy of neuroendoscopic procedures in minimally invasive preferential
      management of pineal region tumors: a prospective study.
AB  - OBJECT: This prospective study is based on a consecutive series of 20 patients
      with pineal region tumors who underwent minimally invasive preferential
      management. The purpose of this report is to discuss the role of neuroendoscopic
      procedures in the management of pineal region tumors. METHODS: If the tumor
      markers alpha-fetoprotein and human chorionic gonadotropin were not detected in
      serum and there was significant ventricular dilation visualized on neuroimages,
      neuroendoscopic surgery was first applied for tumor debulking with tissue
      diagnosis and gross morphological analysis of the tumor and the intraventricular
      structures, followed by third ventriculostomy. Subsequent procedures were
      determined on the basis of verified individual tumors. For treatment of
      germinomas and pineoblastomas, if no tumor dissemination was confirmed by pre-,
      intra-, or postoperative findings, stereotactic radiotherapy or radiosurgery was
      performed after one course of chemotherapy with the ICE regimen (isofomid,
      cisplatin, and etoposide) and followed by two additional courses of chemotherapy.
      For treatment of malignant germ cell tumors, after extensive surgery, adjuvant
      chemotherapy with the ICE regimen was performed in three courses in all cases.
      Then radiotherapy was started using various methods, depending on the evidence of
      tumor dissemination. For treatment of teratomatous and neuroectodermal tumors
      other than pineoblastomas, extensive surgical removal was performed. As for
      adjuvant therapy, if the tumor was a low-grade glioma or if the patient was
      younger than 5 years of age, postoperative treatment did not include
      radiotherapy. If the tumor was a malignant teratoma or high-grade glioma,
      conventional focal radiotherapy was performed, followed by chemotherapy with ICE
      for 1 year. All but two treated patients had ventriculomegaly. Neuroendoscopic
      procedures were performed in six of 15 treated patients. Neuroendoscopic biopsy
      with tumor debulking offered enough material for tissue diagnosis, including
      immunohistochemical analysis and, in one case, revealed evidence of tumor
      dissemination undetectable on neuroimaging. With one exception, no shunt was
      required in any patient undergoing endoscopic third ventriculostomy. Stereotactic
      radiotherapy was performed in indicated cases. Favorable therapeutic outcomes
      were obtained in all cases of germinoma and pineoblastoma, with follow-up periods
      ranging from 24 months to 6.5 years. CONCLUSIONS: Our minimally invasive
      preferential regimen clarified the precise indication for neuroendoscopic
      procedures, and the majority of our patients with dilated ventricles and no
      evidence of tumor markers were treated satisfactorily with effective
      neuroendoscopic procedures as the initial procedure, avoiding unnecessary
      craniotomy and radiotherapy and promising excellent therapeutic outcomes. The
      treatment for malignant pineal region tumors remains a subject for further study.

PMID- 10930011
TI  - Volume-rendered helical computerized tomography angiography in the detection and
      characterization of intracranial aneurysms.
AB  - OBJECT: The goal of this study was to evaluate the utility of volume-rendered
      helical computerized tomography (CT) angiography in patients with intracranial
      aneurysms. The authors compared the abilities of CT angiography, digital
      subtraction (DS) angiography, and three-dimensional time-of-flight magnetic
      resonance (MR) angiography to characterize aneurysms. METHODS: Helical CT
      angiography was performed in 45 patients with suspected intracranial aneurysms by
      using volume-rendered multiplanar reformatted (MPR) images. Digital subtraction
      angiography was performed using biplane angiography. These studies and those
      performed using MR angiography were interpreted in a blinded manner. Two
      neurosurgeons and two interventional neuroradiologists independently graded the
      utility of CT angiography with respect to aneurysm characterization. Fifty-five
      aneurysms were detected. Of these, 48 were evaluated for treatment. Computerized
      tomography angiography was judged to be superior to both DS and MR angiography in
      the evaluation of the arterial branching pattern at the aneurysm neck (compared
      with DS angiography, p = 0.001, and with MR angiography, p = 0.007), aneurysm
      neck geometry (compared with DS angiography, p = 0.001, and with MR angiography,
      p = 0.001), arterial branch incorporation (compared with DS angiography, p =
      0.021, and with MR angiography, p = 0.001), mural thrombus (compared with DS
      angiography, p < 0.001), and mural calcification (compared with DS angiography, p
      < 0.001, and with MR angiography, p < 0.001). For surgical cases, CT angiography
      had a significant impact on treatment path (p = 0.001), operative approach (p =
      0.001), and preoperative clip selection (p < 0.001). For endovascular cases, CT
      angiography had an impact on treatment path (p < 0.02), DS angiography study time
      (p = 0.01), contrast agent usage (p = 0.01), and coil selection (p = 0.02).
      Computerized tomography angiography provided unique information about 39 (81%) of
      48 aneurysms, especially when compared with DS angiography (p = 0.003). The
      sensitivity and specificity of CT angiography compared with DS angiography was 1.
      The sensitivity and specificity of CT and DS angiography studies compared with
      operative findings were 0.98 and 1, respectively. CONCLUSIONS: Computerized
      tomography angiography is equal to DS angiography in the detection and superior
      to DS angiography and MR angiography in the characterization of brain aneurysms.
      Information contained in volume-rendered CT angiography images had a significant
      impact on case management.

PMID- 10930012
TI  - Continuous monitoring of regional cerebral blood flow: experimental and clinical
      validation of a novel thermal diffusion microprobe.
AB  - OBJECT: Current clinical neuromonitoring techniques lack adequate surveillance of
      cerebral perfusion. In this article, a novel thermal diffusion (TD) microprobe is
      evaluated for the continuous and quantitative assessment of intraparenchymal
      regional cerebral blood flow (rCBF). METHODS: To characterize the temporal
      resolution of this new technique, rCBF measured using the TD microprobe (TD-rCBF)
      was compared with rCBF levels measured by laser Doppler (LD) flowmetry during
      standardized variations of CBF in a sheep model. For validation of absolute
      values, the microprobe was implanted subcortically (20 mm below the level of
      dura) into 16 brain-injured patients, and TD-rCBF was compared with simultaneous
      rCBF measurements obtained using stable xenon-enhanced computerized tomography
      scanning (sXe-rCBF). The two techniques were compared using linear regression
      analysis as well as the Bland and Altman method. Stable TD-rCBF measurements
      could be obtained throughout all 3- to 5-hour sheep experiments. During
      hypercapnia, TD-rCBF increased from 49.3+/-15.8 ml/100 g/min (mean +/- standard
      deviation) to 119.6+/-47.3 ml/100 g/ min, whereas hypocapnia produced a decline
      in TD-rCBF from 51.2+/-12.8 ml/100 g/min to 39.3+/-5.6 m/100 g/min. Variations in
      mean arterial blood pressure revealed an intact autoregulation with pressure
      limits of approximately 65 mm Hg and approximately 170 mm Hg. After cardiac
      arrest TD-rCBF declined rapidly to 0 ml/100 g/min. The dynamics of changes in TD
      rCBF corresponded well to the dynamics of the LD readings. A comparison of TD
      rCBF and sXe-rCBF revealed a good correlation (r = 0.89; p < 0.0001) and a mean
      difference of 1.1+/-5.2 ml/100 g/min between the two techniques. CONCLUSIONS: The
      novel TD microprobe provides a sensitive, continuous, and real-time assessment of
      intraparenchymal rCBF in absolute flow values that are in good agreement with sXe
      rCBF measurements. This study provides the basis for the integration of TD-rCBF
      into multimodal monitoring of patients who are at risk for secondary brain
      injury.

PMID- 10930014
TI  - Superficial surgical landmarks for the transverse sinus and torcular herophili.
AB  - OBJECT: The purpose of this anatomical study is to identify reliable external
      landmarks that can be used to determine accurately the lower border of the
      proximal segment of the transverse sinus (TS). METHODS: The authors used 15
      formalin-fixed cadaveric specimens for this project. Various anatomical
      structures were dissected and measurements of the distance between these
      structures and the proximal TS were obtained. The data collected in this study
      demonstrate that the inion is not always a reliable external landmark to use when
      determining the internal location of the very proximal TS and its drainage into
      the area of the torcular herophili. In addition, the authors found that the most
      accurate external landmark to use in reliably estimating the internal placement
      of the proximal TS is the point of insertion of the musculus semispinalis capitus
      and not the superior nuchal line. In the present study, this muscle never covered
      more than 5 mm of the inferior edge of the TS and was found to be a reliable
      anatomical structure for avoiding the medial segment of the TS. CONCLUSIONS:
      These findings could aid the surgeon in localizing the TS with various midline
      approaches to the posterior fossa and the craniocervical junction.

PMID- 10930013
TI  - Survival of adult rat retinal ganglion cells with regrown axons in peripheral
      nerve grafts: a comparison of graft attachment with suture of fibrin glue.
AB  - OBJECT: The goal of this study was to examine whether the method of attachment of
      a peripheral nerve graft would have an effect on retinal ganglion cell (RGC)
      regeneration. METHODS: The number of adult rat RGCs with regrown axons in a
      peripheral nerve graft was compared under two grafting conditions: 1) attachment
      of the graft to the optic nerve stump made using a suture; and 2) attachment made
      using fibrin glue. Counts of RGCs retrogradely labeled with FluoroGold from the
      grafts 1 month after attachment revealed approximately seven times the number of
      RGCs in the fibrin-glue group compared with the suture group. CONCLUSIONS: The
      use of fibrin glue may be a useful tool for enhancing the regrowth of central
      nervous system neuron axons into peripheral nervous system grafts.

PMID- 10930015
TI  - Experimental study of the magnetic stereotaxis system for catheter manipulation
      within the brain.
AB  - OBJECT: The magnetic stereotaxis system (MSS) is a device designed to direct
      catheter tips through magnetic forces. In this study the authors tested the
      safety and performance of the MSS in directing catheters through a nonlinear path
      to obtain biopsy specimens in pig brains. METHODS: Sixteen pigs underwent biopsy
      of the frontal brain region with the aid of an MSS (11 pigs) or a standard
      stereotactic biopsy tool (five pigs). Surgical preparation consisted of placement
      of six fiducial markers in the skull and the creation of a burr hole for
      attachment of a cranial bolt and passage of the biopsy catheter. The pigs
      underwent magnetic resonance (MR) imaging of the head to define a biopsy target
      and to plan a nonlinear path. Guided by the MSS, which used nearly real-time
      fluoroscopic imaging fused to the preoperative MR image, the authors advanced a
      catheter to the biopsy target. A biopsy tool was passed through the catheter and
      a tissue sample was obtained. The animals were observed for 3 to 5 days
      postoperatively, when they were assessed for neurological abnormalities or other
      signs of morbidity. Actual catheter placement was within 1.5 mm of the planned
      path to the biopsy site, using a minimum path radius of 30 mm. The registration
      error associated with the use of the MSS x-ray fluoroscopy and MR imaging
      averaged 1.7 mm. Tissue disruption caused by the MSS was similar to that of
      standard stereotactic procedures. CONCLUSIONS: The MSS affords accurate and safe
      guidance of brain catheters in animals. The application tested here, brain
      biopsy, is one of a number of potential catheter-guided procedures.

PMID- 10930016
TI  - Wild-type p53-dependent etoposide-induced apoptosis mediated by caspase-3
      activation in human glioma cells.
AB  - OBJECT: In an attempt to understand the roles of several apoptosis-related genes
      in human glioma cells, the authors investigated the relationship of wild-type
      p53, interleukin-1beta-converting enzyme (ICE), caspase-3 (CPP32), bax, and bcl-2
      to the apoptotic response of three glioma cell lines after treatment with
      etoposide. METHODS: A human glioma cell line (U-87MG) that expresses wild-type
      p53, one that expresses mutant p53 (T-98G), and a T-98G derivative (T-98G/p53)
      that was transfected with a wild-type p53 expression vector (pCDM8-p53/neo) were
      used. Cell growth inhibition in response to etoposide was quantified using a
      modified methylthiazol tetrazolium colorimetric assay. Induction of apoptosis was
      evaluated using Hoechst 33258 staining and a DNA fragmentation assay. To study
      the expression of the apoptosis-related proteins and messenger RNAs in the three
      glioma cell lines, Western blotting and polymerase chain reaction were performed.
      A caspase assay and Western blot analysis were used to assess CPP32 and ICE
      protease activity. A CPP32 inhibition assay was used to determine whether a
      specific CPP32 inhibitor, DEVD-CHO, affects the apoptosis induced by etoposide in
      malignant glioma cells. Etoposide significantly inhibited the growth of U-87MG
      and T-98G/p53 cells in a dose-dependent manner compared with the growth of the T
      98G cells. Treatment with low concentrations of etoposide resulted in the
      increased expression of wild-type p53; it also initiated CPP32 activity and
      induced apoptosis in the U-87MG cells. Apoptosis was not induced in T-98G cells
      at low concentrations of etoposide, although it was induced at high
      concentrations. Furthermore, low concentrations of etoposide also induced
      apoptosis in the T-98G/p53 cells by enhancing the expression of transfected wild
      type p53, decreasing the expression of bcl-2, and activating CPP32 activity.
      However, etoposide did not alter the expression of bax and did not initiate ICE
      activity in these three glioma cell lines. Etoposide-induced apoptosis can be
      suppressed by the CPP32 inhibitor DEVD-CHO. CONCLUSIONS: These findings indicate
      that wild-type p53, CPP32, and bcl-2 may mediate apoptosis induced by etoposide.
      Forced expression of wild-type p53 increases etoposide cytotoxicity in human
      glioma cells by inducing apoptosis and may have important therapeutic
      implications.

PMID- 10930017
TI  - Effect of age on cerebral venous circulation disturbances in the rat.
AB  - OBJECT: Mild cerebral venous circulation disturbances (CVCDs) in aged patients
      are frequently known to cause unexpectedly severe postoperative complications in
      neurosurgical practice. The object of the present study was to determine whether
      there are age-related differences involved in vulnerability to CVCDs. METHODS:
      Thirty-eight male Wistar rats were used. A single cortical vein with a 100-microm
      diameter was occluded photochemically by using rose bengal dye and fiberoptic
      illumination in young (Group Y, 19 animals aged 10-14 weeks) and aged (Group A,
      seven animals aged 80-100 weeks) rats. Five young and seven aged animals served
      as sham-operated controls. Regional cerebral blood flow (rCBF) was determined
      from local CBF, which was measured at 25 (5 x 5) identical locations, with the
      occluded vein located central to the scanning field, by using a laser Doppler
      scanning technique every 15 minutes for 90 minutes after venous occlusion. The
      cerebral venous flow pattern was examined using fluorescence angiography until 90
      minutes after occlusion. Histological specimens were examined 24 hours after
      occlusion. In Group Y, rCBF did not change significantly after venous occlusion.
      However, in Group A, rCBF decreased rapidly beginning 15 minutes after occlusion.
      Significant intergroup differences were observed 30, 60, and 90 minutes after
      occlusion. Venous flow arrest, which resulted in venous infarct, was observed on
      angiography 90 minutes after occlusion in two (10.5%) of 19 young and six (85.7%)
      of seven aged rats. The venous thrombus in Group A rats was significantly larger
      than that in Group Y rats 90 minutes after occlusion. Venous infarction was seen
      in all aged rats (100%) and in six young rats (31.6%); the infarct size,
      expressed as a percentage of the size of the ipsilateral hemisphere, was
      significantly larger in aged rats than in young rats. CONCLUSIONS: This study
      demonstrated an age-related increase in the rate and size of venous infarct
      following vein occlusion, suggesting that the greater vulnerability to CVCDs in
      the aged brain might be attributed to early and extensive hypoperfusion of
      circumscribed brain areas drained by the occluded vein. The larger thrombus
      formation in aged animals indicates that a shift in the
      thrombogenetic/thrombolytic equilibrium is responsible for the observed effect.

PMID- 10930018
TI  - Effect of initially limited resuscitation in a combined model of fluid-percussion
      brain injury and severe uncontrolled hemorrhagic shock.
AB  - OBJECT: Studies of isolated uncontrolled hemorrhage have indicated that initial
      limited resuscitation improves survival. Limited resuscitation has not been
      studied in combined traumatic brain injury and uncontrolled hemorrhage. In this
      study the authors evaluated the effects of limited resuscitation on outcome in
      combined fluid-percussion injury (FPI) and uncontrolled hemorrhage. METHODS:
      Twenty-four swine weighing 17 to 24 kg each underwent FPI (3 atm) and hemorrhage
      to a mean arterial pressure (MAP) of 30 mm Hg in the presence of a 4-mm aortic
      tear. Group I (nine animals) was initially resuscitated to a goal MAP of 60 mm
      Hg; Group II (nine animals) was resuscitated to a goal MAP of 80 mm Hg; and Group
      III (control; six animals) was not resuscitated. After 60 minutes, the aortic
      hemorrhage was controlled and the animals were resuscitated to baseline
      physiological parameters and observed for 150 minutes. Mortality rates were 11%,
      50%, and 100% for Groups I, II, and III, respectively (Fisher's exact test; p =
      0.002). The total hemorrhage volume was greater in Group II (69+/-32 ml/kg), as
      compared with Group I (41+/-18 ml/kg) and Group III (37+/-3 ml/kg) according to
      analysis of variance (p < 0.05). In surviving animals, cerebral perfusion
      pressure, cerebral blood flow (CBF), cerebral venous O2 saturation (ScvO2), and
      cerebral metabolic rate of O2 did not differ among groups. Although CBF was
      approximately 50% of baseline during the period of limited resuscitation in Group
      I, ScvO2 remained greater than 60%, and arteriovenous O2 differences remained
      within normal limits. CONCLUSIONS: In this model of FPI and uncontrolled
      hemorrhage, early aggressive resuscitation, which is currently recommended,
      resulted in increased hemorrhage and failure to optimize cerebrovascular
      parameters. In addition, a 60-minute period of moderate hypotension (MAP = 60 mm
      Hg) was well tolerated and did not compromise cerebrovascular hemodynamics, as
      evidenced by physiological parameters that remained within the limits of cerebral
      autoregulation.

PMID- 10930019
TI  - Immediate coma following inertial brain injury dependent on axonal damage in the
      brainstem.
AB  - OBJECT: Immediate and prolonged coma following brain trauma has been shown to
      result from diffuse axonal injury (DAI). However, the relationship between the
      distribution of axonal damage and posttraumatic coma has not been examined. In
      the present study, the authors examine that relationship. METHODS: To explore
      potential anatomical origins of posttraumatic coma, the authors used a model of
      inertial brain injury in the pig. Anesthetized miniature swine were subjected to
      a nonimpact-induced head rotational acceleration along either the coronal or
      axial plane (six pigs in each group). Immediate prolonged coma was consistently
      produced by head axial plane rotation, but not by head coronal plane rotation.
      Immunohistochemical examination of the injured brains revealed that DAI was
      produced by head rotation along both planes in all animals. However, extensive
      axonal damage in the brainstem was found in the pigs injured via head axial plane
      rotation. In these animals, the severity of coma was found to correlate with both
      the extent of axonal damage in the brainstem (p < 0.01) and the applied kinetic
      loading conditions (p < 0.001). No relationship was found between coma and the
      extent of axonal damage in other brain regions. CONCLUSIONS: These results
      suggest that injury to axons in the brainstem plays a major role in induction of
      immediate posttraumatic coma and that DAI can occur without coma.

PMID- 10930020
TI  - Adult rhombencephalosynapsis. Case report.
AB  - Rhombencephalosynapsis (RS) is a relatively rare developmental disorder of the
      cerebellum in which the cerebellar hemispheres are fused across the midline
      without being separated by a cleft or the vermis. The condition may be associated
      with hydrocephalus and other intracranial and extracranial abnormalities. The
      authors report on the case of a symptomatic adult who was successfully treated
      with suboccipital decompression and duraplasty. A 39-year-old woman presented
      with intractable pain radiating from the thoracolumbar column to the occiput. A
      general examination yielded normal findings and a neurological examination
      revealed only subtle ataxia of tandem gait. The patient underwent magnetic
      resonance (MR) imaging, the results of which revealed an absent cerebellar vermis
      with fusion of the cerebellum and mild hydrocephalus. A cine-MR image obtained to
      evaluate her cerebrospinal fluid flow (CSF) revealed attenuated flow in the
      posterior fossa and cerebral aqueduct. Preoperative intracranial pressure (ICP)
      monitoring demonstrated no elevation of ICP (mean 4.3 mm Hg). The patient
      consented to undergo suboccipital craniectomy and duraplasty. Despite an increase
      in postoperative ICP (mean 10.77 mm Hg; difference from preoperative level
      according to a t-test, p = 0.002), the patient experienced symptomatic relief,
      which has persisted for 3 years. One year postoperatively, a cine-MR image was
      obtained, which revealed improvement in the patient's CSF dynamics. The authors
      conclude that, although RS may cause altered flow in the adult, their patient has
      experienced symptomatic relief, suggesting that her pain was related to local
      pressure in the posterior fossa.

PMID- 10930021
TI  - Successful neuroendoscopic third ventriculostomy for hydrocephalus and
      syringomyelia associated with fourth ventricle outlet obstruction. Case report.
AB  - The authors report the use of neuroendoscopic third ventriculostomy to treat
      successfully both hydrocephalus and syringomyelia associated with fourth
      ventricle outlet obstruction. A 27-year-old woman presented with dizziness,
      headache, and nausea. Magnetic resonance (MR) imaging demonstrated dilation of
      all ventricles, downward displacement of the third ventricular floor,
      obliteration of the retrocerebellar cerebrospinal fluid (CSF) space, funnellike
      enlargement of the entrance of the central canal in the fourth ventricle, and
      syringomyelia involving mainly the cervical spinal cord. Cine-MR imaging
      indicated patency of the aqueduct and an absent CSF flow signal in the area of
      the cistema magna, which indicated obstruction of the outlets of the fourth
      ventricle. Although results of radioisotope cisternography indicated failure of
      CSF absorption, neuroendoscopic third ventriculostomy completely resolved all
      symptoms as well as the ventricular and spinal cord abnormalities evident on MR
      images. Neuroendoscopic third ventriculostomy is an important option for treating
      hydrocephalus in patients with fourth ventricle outlet obstruction.

PMID- 10930022
TI  - Medulloblastomas with extensive posttherapy neuronal maturation. Report of two
      cases.
AB  - The authors report on two patients with classic medulloblastoma, each of whom
      underwent extensive therapy-associated neuronal maturation. The first patient
      presented at 3 months of age with hydrocephalus caused by a 5-cm tumor in the
      cerebellar vermis. He underwent a gross-total resection of a desmoplastic
      medulloblastoma. No mature elements were identified. Despite adjuvant
      chemotherapy, a 1.5-cm recurrent tumor developed 6 months later. Sections from
      the subtotally resected tumor demonstrated exclusively mature neuronal elements,
      ranging from neurocytes to ganglion cells. Four months later, a second recurrent
      tumor was resected. The specimen collected this time demonstrated classic
      medulloblastoma morphological characteristics. The patient was subsequently
      treated with radiation therapy, which seemed to have an effect; however, the
      tumor eventually progressed and the patient died. The second patient presented at
      3 years of age with a midline medulloblastoma and was treated with subtotal
      resection, radiation therapy, and chemotherapy. Although the tumor remained
      stable on radiographic imaging, a second resection was performed 8 years later to
      alleviate hydrocephalus. Histological examination revealed predominantly small
      mature neurons with scattered ganglion cells and extensive calcification. No
      adjuvant therapy was given and the patient is alive and well as of his last
      follow-up examination. The mature neuronal neoplasms resected in both patients
      demonstrated negligible proliferative indices and stained appropriately with
      neuronal immunohistochemical markers. The smaller neuronal population resembled
      those of a central neurocytoma and medullocytoma/cerebellar neurocytoma.
      Analogous to neuroblastoma, our cases suggest that adjuvant therapy can induce
      extensive or complete neuronal maturation in medulloblastoma. Additional cases
      must be studied to determine the prognostic significance of this rare phenomenon.

PMID- 10930023
TI  - Multiple intracranial juvenile xanthogranulomas. Case report.
AB  - The authors report on an 11-year-old boy in whom proptosis of the eye caused by a
      benign intraosseous xanthofibroma of the left orbital wall became clinically
      apparent at the age of 4 years. Two years later he developed bilateral
      papilledema, at which time computerized tomography and magnetic resonance studies
      revealed multiple enhancing intracranial lesions. The largest mass was located in
      the left middle fossa; other lesions were located at the tentorium cerebelli, in
      both lateral ventricles, near the superior sagittal sinus, and extracranially
      near the left jugular vein. The mass in the left middle fossa was resected and
      diagnosed as juvenile xanthogranuloma (JXG). Thirty months later, the patient
      again became symptomatic, exhibiting behavioral abnormalities and a decrease in
      mental powers. At that time, the two remaining lesions in both lateral ventricles
      had grown enough to cause trapping of the temporal horns and raised intracranial
      pressure. These lesions were successively resected and histopathologically
      confirmed to be JXGs. However, resection of the second intraventricular lesion
      was complicated by postoperative bilateral amaurosis, presumably caused by
      postdecompression optic neuropathy. According to a review of the literature,
      fewer than 20 patients with JXG involving the central nervous system have been
      reported. The patient described in this report is the first in whom multiple
      intracranial JXGs developed in the absence of cutaneous manifestations. Although
      JXGs are biologically benign lesions, the treatment of patients with multifocal
      and/or progressive intracranial manifestations is problematic.

PMID- 10930024
TI  - Virtual image navigation: a new method to control intraoperative bleeding in
      neuroendoscopic surgery. Technical note.
AB  - In this neuroendoscopic study the authors tested the newly developed "red-out
      module" of their visual navigation system that enables the neurosurgeon to
      achieve hemostasis if total visualization is lost due to hemorrhage ("red out")
      within the visual field. An optical position measurement system connected to the
      endoscope guarantees that digitized endoscopic images are coupled with the
      accurate endoscopic position. Computerized images are simultaneously stored with
      their respective position data, and this creates a virtual anatomical landscape.
      The system was tested in in vivo bleeding conditions in a rat model. Artificial
      endoscopic cavities were created in the inguinal, pelvic, and jugular regions in
      rats to imitate the conditions of the human ventricular system. Two experimental
      settings were tested: Technique I, in which a computer landmark has been
      previously determined at the point where the vessel will be lesioned; and
      Technique II, in which a landmark has been previously set in the surrounding area
      of the vessel. Immediately after hemorrhage obscures the visual field (red out),
      the computer automatically displays the virtual images on a separate monitor. The
      previously set landmarks and the graphic overlay of the coagulation fiber enable
      the surgeon to navigate within the operative field based on the virtual images
      and to perform coagulation at the site of the lesion. A total of 175 vessels were
      coagulated: 43 arteries and 132 veins. In using Technique I, 130 (90.9%) of 143
      vessels and in using Technique II, 26 (81.2%) of 32 arteries were successfully
      coagulated. The authors' data revealed that virtual image guidance has the
      potential to be a helpful tool in neuroendoscopy.

PMID- 10930025
TI  - Comparison of two commercially available near-infrared spectroscopy instruments
      for cerebral oximetry. Technical note.
AB  - Two near-infrared spectroscopy (NIRS) devices were compared with regard to their
      responses to changes in cerebral hemoglobin oxygenation induced by hypoxia and
      hypercapnia in five healthy volunteers. Sensors belonging to each NIRS device
      were placed on opposite sides of the volunteer's forehead. The INVOS-3100A
      device, approved by the United States Food and Drug Administration, records the
      percentage of oxyhemoglobin (HbO2) saturation and the investigational NIRO500
      device records absolute changes in HbO2, deoxyhemoglobin, and total hemoglobin in
      micromolar concentrations referenced to an arbitrary baseline. The volunteers
      breathed separate mixtures of 7% CO2 in O2 and 10% O2 for 5 minutes in random
      order. Arterial blood pressure, end-tidal CO2 (ETCO2), arterial O2 saturation,
      and electrocardiographic data were continuously monitored. Hypercapnia increased
      (p < 0.01) ETCO2 from 42+/-2 to 56+/-3 mm Hg (mean +/- standard deviation),
      resulting in a 7.3+/-0.2% increase (p < 0.005) in cerebral HbO2 saturation
      detected by the INVOS3100A device and an 11.6+/-3 microM increase (p < 0.0008) in
      HbO2 detected by the NIRO500. Hypoxia decreased (p < 0.01) arterial HbO2
      saturation from 98+/-1 to 87+/-3%, causing a 5.1+/-1.2% decrease (p < 0.01) in
      the percentage of HbO2 saturation detected by the INVOS3100A device and a 9.7+/
      6.3 microM decrease in HbO2 detected by the NIRO500. The responses of the NIRO500
      and the INVOS3100A instruments to changes in cerebral oxygenation resulting from
      hypercapnia and hypoxia were generally similar; however, responses tended to be
      greater when recorded by the NIRO500 device, perhaps because, unlike the
      INVOS3100A device, the NIRO500 does not correct for skin and bone contamination.

PMID- 10930026
TI  - Simulation of the surgical manipulation involved in clipping a basilar artery
      aneurysm: concepts of virtual clipping. Technical note.
AB  - Despite recent advances in three-dimensional imaging based on a voxel-rendering
      method, these techniques do not simulate the morphological changes that occur
      during surgery. The authors' goal was to develop a computer-graphics model to
      simulate the manipulation that occurs during surgery when clipping a cerebral
      aneurysm. The authors developed an application program to interpolate the
      contours of models of an artery and an aneurysm clip. The center of displacement
      was determined inside the arterial model. The directions of displacement were
      changed to simulate saccular and broad-neck aneurysms, and the intensity of
      displacement was calculated by using a cosine-based formula. The morphological
      changes in a saccular aneurysm that may occur during clipping were calculated in
      x, y, and z coordinates by using sine- and cosine-based formulas. Clip movement
      was integrated with the aneurysm model, thus simulating the manipulation used
      during clipping of a cerebral aneurysm. Surgery performed to clip a basilar
      artery (BA) aneurysm via the transsylvian approach was simulated, in which
      displacement of the internal carotid artery and clipping of the BA aneurysm were
      necessary. The movements of an aneurysm clip and clip applicator were designed to
      represent those occurring when a surgeon actually manipulates a BA aneurysm. The
      authors have named this methodological tool "virtual clipping." Use of this tool
      would assist the preoperative choice of clipping style and selection of the best
      clip.

PMID- 10930027
TI  - Endarterectomy and anesthesia.

PMID- 10930029
TI  - Osteoblastic meningioma.

PMID- 10930028
TI  - Excitotoxic ablation.

PMID- 10930030
TI  - Basilar artery anatomy.

PMID- 10930031
TI  - Hemorrhagic colloid cyst.

PMID- 10930032
TI  - Oxyhemoglobin and intracellular calcium.

PMID- 10930033
TI  - Aneurysm clip slippage.

PMID- 10930034
TI  - Wide-necked basilar artery bifurcation aneurysm.

PMID- 10930036
TI  - Morphological changes in the kidney of dogs chronically exposed to exogenous
      growth hormone.
AB  - Porcine growth hormone was administered subcutaneously to beagle dogs at doses of
      0.025, 0.1, and 1 IU/kg/d for 14 weeks, markedly elevating serum growth hormone
      (GH) and insulin-like growth factor-1 (IGF-1) levels. This was accompanied by a
      significant increase in body weight gain and kidney weights in both male and
      female dogs. The increase in kidney weight (6 to 54%) was slightly greater than
      the increase in body weight (6 to 40%). By light microscopy, glomerular deposits,
      mesangial thickening, and very slight cellular infiltration in glomeruli were
      seen in mid- and high-dose groups. Based on morphometric evaluation, there was an
      increase in the renal glomerular area, which was statistically significant (p <
      or = 0.05) in the mid- and high-dose males and in the high-dose females. This was
      associated with a statistically significant (p < or = 0.05) increase in the
      number of total glomerular cells in the mid- and high-dose males. By transmission
      electron microscopy, thickening of the glomerular basal lamina and diffuse
      increase of the mesangial matrix were observed in both male and female dogs in
      the mid- and high-dose groups. Immunohistochemical reactions were negative for
      IgG, IgM, and C3. The morphological changes in the kidney of dogs resemble the
      diffuse glomerulosclerosis described in human diabetic nephropathy.

PMID- 10930035
TI  - The nongenotoxic hepatocarcinogens diethylhexylphthalate and methylclofenapate
      induce DNA synthesis preferentially in octoploid rat hepatocytes.
AB  - Diethylhexylphthalate (DEHP), a rodent carcinogen, and 1,4-dichlorobenzene (DCB),
      a noncarcinogen in rat liver, are potent hepatomitogens. We have reported
      previously that 7-day dosing with DEHP induced a higher bromodeoxyuridine
      labeling index (LI) in binuclear octoploid (2x4N) rat hepatocytes than did DCB,
      suggesting that induction of DNA synthesis in 2x4N hepatocytes might represent a
      more substantial carcinogenic risk. We compared 2 additional rodent
      hepatocarcinogens, methylclofenapate (MCP) and phenobarbitone, with ethylene
      thiourea (ETU), a noncarcinogenic hepatomitogen in rat. All 3 chemicals increased
      hepatic LI; the 8N population had the highest LI, but only the carcinogens
      increased LI in the 2x4N and 4N populations. To identify the target population
      for induction of DNA synthesis, we used a 1-hour pulse label at the peak of
      induction. The results were consistent with the 7-day data, and again the highest
      LI was in the 8N population. The nongenotoxic rodent carcinogens MCP and DEHP
      induced a significant increase in the LI in the 2x4N population, whereas ETU and
      DCB did not. These data support the hypothesis that increased DNA synthesis
      within the minority 2x4N population may be more significant for subsequent
      hepatocarcinogenesis.

PMID- 10930037
TI  - CyA-mediated renal interstitial and vascular lesions in the rat under low-sodium
      diet.
AB  - Nephrotoxicity of CyA was analyzed histologically in rats fed a low-sodium diet.
      CyA was subcutaneously administered daily at a dose of 15 mg/kg for 10 or 35 days
      with or without prior uninephrectomy (UNT) in male Sprague-Dawley rats receiving
      a low-sodium diet (0.03% sodium). CyA-administered rats showed impaired renal
      function as well as tubulo-interstitial lesions, such as edema, tubular basement
      membrane changes, and tubular atrophy, in the cortex, especially in the
      subcapsular portion, within 10 days. On day 35, the tubulo-interstitial lesions
      were advanced with mild focal interstitial fibrosis. These lesions were mild in
      the UNT group compared to the non-UNT group. Immunohistochemically, CyA treatment
      caused an increase in number of renin-positive cells in the afferent arteriolar
      wall at juxtaglomerular area. These cells lost the expression of calponin, which
      is a marker of mature smooth muscle cells. In addition, in afferent arterioles
      and interlobular arteries, electron-dense fibrous bodies were found in the smooth
      muscle cells on days 10 and 35. Immunoelectron microscopically, these bodies
      showed scattered positive staining for calponin and alpha-actinin, were negative
      or only peripherally positive for alpha-SMA and vimentin, and were completely
      negative for desmin. This study revealed that CyA could cause interstitial
      lesions starting in the subcapsular portion of the renal cortex and vascular
      lesions of the preglomerular artery. Increases in number of renin granules and
      formation of cytoplasmic fibrous bodies in smooth muscle cells could be the
      forerunner of severe arteriolar wall damage.

PMID- 10930038
TI  - Mutations of ras protooncogenes and p53 tumor suppressor gene in cardiac
      hemangiosarcomas from B6C3F1 mice exposed to 1,3-butadiene for 2 years.
AB  - 1,3-Butadiene is a multisite carcinogen in rodents. Incidences of cardiac
      hemangiosarcomas were significantly increased in male and female B6C3F1 mice that
      inhaled 1,3-butadiene (BD) for 2 years. Eleven BD-induced cardiac
      hemangiosarcomas were examined for genetic alterations in ras protooncogenes and
      in the p53 tumor suppressor gene. Nine of 11 (82%) BD-induced hemangiosarcomas
      had K-ras mutations and 5 of 11 (46%) had H-ras mutations. All of the K-ras
      mutations were G-->C transversions (GGC-->CGC) at codon 13; this pattern is
      consistent with reported results in BD-induced lung neoplasms and lymphomas. Both
      K-ras codon 13 CGC mutations and H-ras codon 61 CGA mutations were detected in 5
      of 9 (56%) hemangiosarcomas. The 11 hemangiosarcomas stained positive for p53
      protein by immunohistochemistry and were analyzed for p53 mutations using cycle
      sequencing of polymerase chain reaction (PCR) amplified DNA isolated from
      paraffin-embedded sections. Mutations in exons 5 to 8 of the p53 gene were
      identified in 5 of 11 (46%) hemangiosarcomas, and all of these were from the 200-
      or 625-ppm exposure groups that also had K-ras codon 13 CGC mutations. Our data
      indicate that K-ras, H-ras, and p53 mutations in these hemangiosarcomas most
      likely occurred as a result of the genotoxic effects of BD and that these
      mutations may play a role in the pathogenesis of BD-induced cardiac
      hemangiosarcomas in the B6C3F1 mouse.

PMID- 10930039
TI  - Dual effects of prolonged ACTH stimulation on 4-hydroxyaminoquinoline 1-oxide
      induced adrenocortical lesions in rats.
AB  - The effects of a long-acting synthetic ACTH on 4-hydroxyaminoquinoline 1-oxide
      (4HAQO)-induced adrenocortical lesions were investigated in female rats. A total
      of 140 6-week-old rats were divided into 4 equal groups, given a single s.c.
      injection of 7 mg/kg 4HAQO or vehicle, followed by repeated sc administration of
      the synthetic ACTH or no further treatment. Subgroups of 10 rats in each group
      were sequentially sacrificed at weeks 20, 30, and 40. Adenomas and adenomatous
      nodules developed in the adrenal cortex of animals receiving 4HAQO and the
      chronic ACTH stimulation. Both lesions were located in the deeper zones of the
      adrenal cortex adjacent to the medulla and were composed of large-sized, clear
      type cells. From week 20, middle zone, cortical cystic degeneration, which mimics
      the age-associated degenerative change named adrenal peliosis, was frequently
      observed in the adrenal glands of animals treated with 4HAQO alone. Its
      development was inhibited by ACTH. In the control animals, peliotic changes
      occurred at low incidence and only at the termination of experiment. These
      results indicate that long-term stimulation of ACTH promotes the development of
      adrenocortical tumors but suppresses the occurrence of adrenal peliosis in rats
      treated with 4HAQO.

PMID- 10930040
TI  - Liver tumor-promoting effect of beta-naphthoflavone, a strong CYP 1A1/2 inducer,
      and the relationship between CYP 1A1/2 induction and Cx32 decrease in its
      hepatocarcinogenesis in the rat.
AB  - Interrelationships among induction of cytochrome P-450 (CYP) 1A1/2, decrease in
      connexin 32 (Cx32), and liver tumor-promoting activity by beta-naphthoflavone
      (BNF) in the promotion stage were examined in a 2-stage liver carcinogenesis
      model. A total of 20 male Fischer 344 rats were initiated with a single
      intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DEN) or were given
      the saline vehicle alone. Starting 2 weeks later, they were fed a diet containing
      2%, 1%, or 0% BNF for 6 weeks. All animals were subjected to a two-thirds partial
      hepatectomy at week 3 and were sacrificed at week 8. Absolute and relative liver
      weights were significantly increased in the DEN+BNF groups as compared to the DEN
      alone group. Diffuse hepatocellular hypertrophy with cytoplasmic eosinophilia,
      sometimes accompanied by development of adenoma-like hepatic foci, was observed
      in the BNF-treated rats. Remarkable induction of cytochrome CYP 1A1/2 and
      significant increase in CYP 2E1 were noted in the DEN+BNF groups, and positive
      immunohistochemical staining for both was observed diffusely. The areas of Cx32
      positive spots per hepatocyte in the centrilobular areas of livers of the BNF
      treated rats were significantly decreased, but no changes were observed in
      periportal areas. The numbers and areas of foci positive for glutathione S
      transferase placental form were increased in the BNF-treated groups. These
      results suggest that BNF is a liver tumor promoter that, unlike phenobarbital,
      does not induce CYP 2B1/2 isozymes, and there seems to be no direct relationship
      between CYP 1A1/2 induction and Cx32 reduction in BNF hepatocarcinogenesis.

PMID- 10930041
TI  - Overexpression of Grb2 in inflammatory lesions and preneoplastic foci and tumors
      induced by N-nitrosodimethylamine in Helicobacter hepaticus-infected and 
      noninfected A/J mice.
AB  - Growth factors bind to membrane receptor tyrosine kinases, resulting in
      autophosphorylation and subsequent binding to proteins with SH2 domains,
      including growth factor receptor-bound protein 2 (Grb2). Grb2 bridges receptors
      to tyrosine kinase substrates such as SHC and SOS, which in turn facilitate the
      activation of downstream signaling pathways, including Ras and mitogen-activated
      protein kinase (MAPK). Overexpression of Grb2 has been demonstrated in several
      types of neoplasia but has not been investigated in liver tumorigenesis. Here we
      investigated Grb2 expression in liver lesions in N-nitrosodimethylamine (NDMA)
      treated Helicobacter hepaticus-infected and -noninfected A/J mice at 1 year of
      age. Previously, we reported (6) that infection promotes the development of these
      NDMA-initiated tumors. In controls, Grb2 immunostaining was absent from normal
      hepatic tissues, whereas the inflammatory lesions in infected livers were
      positive for cytoplasmic Grb2 in both hepatocytes and infiltrating leukocytes.
      All preneoplastic foci (7 of 7), 15 of 27 adenomas, and 3 of 7 carcinomas were
      positive for Grb2 by immunostaining in both infected and noninfected NDMA
      initiated livers. Involvement of Grb2 was confirmed by immunoblotting of
      similarly infected mice at 9 to 18 months of age, showing a 2.5- to 3.3-fold
      increase in Grb2 protein in infected livers (p < 0.05 compared with uninfected
      controls) as well as in preneoplastic foci, adenomas, and carcinomas. These
      livers also showed a 2.5- to 2.8-fold increase in total Ras protein. The results
      suggest that upregulation of Grb2 is an early event in liver carcinogenesis,
      whether caused by the bacterial infection or by NDMA. Concomitant upregulation of
      Ras p21 would ensure transmission of amplified signal from growth factors via
      Grb2.

PMID- 10930042
TI  - Cataractogenesis in neonatal Sprague-Dawley rats by N-methyl-N-nitrosourea.
AB  - Cataract was induced by a single intraperitoneal injection of 100 mg/kg N-methyl
      N-nitrosourea (MNU) to 0-, 5-, 10-, 15-, or 20-day-old male and female Sprague
      Dawley rats. In day 0, 5, 10, and 15 MNU-treated rats, mature cataracts were
      constantly seen 7, 14, 14, and 30 days after dosing, respectively. In the day 20
      MNU-treated rats, only subcapsular cataract was seen 30 days after dosing.
      Therefore, the rats exposed to MNU at an earlier age caused cataract more rapidly
      and severely. In the day 0 MNU-treated rats, 7-methyldeoxyguanosine DNA adduct
      was detected in the lens epithelial nuclei 12 hours after MNU dosing, followed by
      apoptosis, which was confirmed by morphology, by TUNEL signals, and by DNA ladder
      and peaked 3 days after MNU dosing. In the apoptosis cascade, upregulation of
      Bax, downregulation of Bcl-2, and increased CPP32 protease (caspase-3) activity
      were seen 12 hours after MNU dosing. Therefore, the pathogenesis of MNU-induced
      cataract was associated with DNA adduct formation in the lens epithelial cell
      nuclei leading to apoptosis by upregulation of Bax protein, downmodulation of Bcl
      2 protein, and activation of caspase-3.

PMID- 10930043
TI  - Detrusor myopathy in young beagle dogs.
AB  - Hematoxylin and eosin-stained sections of urinary bladder were examined
      microscopically from 449 male and female beagle dogs after 2- to 4-week
      toxicology studies. Degenerative lesions (detrusor myopathy) of the urinary
      bladder muscular tunic were present in 59 of 449 (13%) dogs. Myopathic lesions
      consisted of focal to multifocal areas of smooth muscle fiber atrophy with
      cytoplasmic basophilia and vacuolation, individual cell necrosis, enlarged smooth
      muscle nuclei and nucleoli, and occasional mitotic figures. Adjacent areas of
      arteritis and periarteritis were present in 10 of 59 (17%) beagles with detrusor
      myopathy suggesting a possible ischemic pathogenesis of the smooth muscle
      lesions. There was no significant difference in prevalence of myopathy in beagles
      administered vehicle or various test compounds. Prior urinary catheterization
      procedures appeared to augment the prevalence of myopathy; some lesions were
      adjacent to minor, iatrogenically traumatized urinary bladder mucosa. Muscle
      lesions were not observed in urinary bladders from mongrel dogs, monkeys, cats,
      rats, or microswine. When compared to crossbred dogs and other laboratory
      species, the beagle dog thus appears to be sensitive to development of detrusor
      myopathy.

PMID- 10930044
TI  - Morphogenesis of craniopharyngeal derivatives in the neurohypophysis of Fisher
      344 rats: abnormally developed epithelial tissues including parotid glands
      derived from the stomatodeum.
AB  - Morphogenesis of craniopharyngeal derivatives of the neurohypophysis found in 14
      Fischer 344 (F344) rats was studied. The incidence of the craniopharyngeal
      derivatives was 0.17% in male (7 out of 4,200) and 0.16% in female (7 out of
      4,450) F344 rats. Neither a sex-related difference in their incidence nor a
      strain-related difference in their morphological features was observed.
      Craniopharyngeal derivatives were composed of aberrant epithelial structures
      consisting of serous acinar and tubular and fusiform cell structures, and most of
      these derivatives were associated with Rathke's cleft cysts, which are suggestive
      of a congenital background. The acinar structures were positive for periodic acid
      Schiff reaction and negative for Alcian blue stain. Immunohistochemically, cells
      forming these structures were positive for cytokeratin, and basal cells of the
      acinar or tubular structures and some of the fusiform cells showed positive
      staining for alpha-smooth muscle actin. Electron microscopically, these spindle
      shaped basal cells had intracytoplasmic myofilaments with focal density in their
      cytoplasm, and they were regarded to be myoepithelial cells. These findings
      strongly indicate that the craniopharyngeal derivatives are not a neoplastic
      lesion but rather are a developmental aberration derived from the stomatodeum,
      which is known to be the origin of both nasal and oral epithelial tissues,
      including the parotid glands, other than Rathke's pouch.

PMID- 10930046
TI  - Effects of antioxidants apocynin and the natural water-soluble antioxidant from
      spinach on cellular damage induced by lipopolysaccaride in the rat.
AB  - Oxidative damage plays a key role in septic shock induced by the endotoxin
      lipopolysaccaride (LPS) by enhancing the formation of reactive oxygen species
      such as superoxide anion radicals, peroxides, and their secondary product,
      malondialdehyde, especially in the liver. In this study, histopathologic changes
      in several organs were compared among groups of male Wistar rats that had been
      injected with LPS following prophylactic pretreatment with either of 2
      antioxidants, a group that had been injected with LPS without pretreatment with
      antioxidants, an untreated control group, and groups that had been injected with
      either of the 2 antioxidants only. The antioxidants used were a water-soluble
      natural antioxidant from spinach (NAO) and the NADPH oxidase inhibitor apocynin.
      Hematoxylin-and-eosin-stained slides were prepared, and lesions were
      semiquantitatively scored. Exposure to LPS alone was associated with multifocal
      hepatocellular necrosis and acute inflammation, thymic and splenic lymphoid
      necrosis, ocular retinal hemorrhage and acute endophthalmitis, adrenal medullary
      vacuolation and necrosis and acute inflammation, and decreased adrenal cortical
      cytoplasmic vacuolation (consistent with depletion of steroidal hormone
      contents). Results indicated that pretreatment with both antioxidants for 8 days
      reduced, in some organs, the necrotic and inflammatory changes associated with
      the LPS challenge. These findings suggest a potential therapeutic application for
      these antioxidants in clinical sepsis.

PMID- 10930045
TI  - Possible involvement of bcl-2 suppression in wild-type p53 gene-dependent cell
      growth repression in rat osteosarcoma cells.
AB  - We recently obtained 3 cloned cell lines demonstrating the p53 mutation from a
      lung metastatic nodule of a rat transplantable osteosarcoma. In this study, we
      applied wild-type p53 gene transfer to the rat osteosarcoma cells by lipofection
      to investigate the effects on cell growth, expression of genes such as waf1/p21,
      bcl-2, and bax, and nucleosomal DNA fragmentation due to apoptosis.
      Reconstitution of the p53 gene inhibits cellular growth, and this growth
      suppressive effect is partly due to apoptosis involving bcl-2 gene suppression in
      this tumor type. This rat osteosarcoma model is similar in biologic behavior to
      human cases and thus is very suitable for further investigation of tumorigenesis
      and gene therapy for osteosarcoma.

PMID- 10930048
TI  - Apoptosis, PCNA, and p53 in Fundulus grandis fish liver after in vivo exposure to
      N-methyl-N'-nitro-N-nitrosoguanidine and 2-aminofluorene.
AB  - Dysfunction in homeostatic mechanisms of cell death and proliferation are
      considered to be important in the pathogenesis of chemically induced neoplasia.
      p53 has been implicated in the regulation of cell death and proliferation. To
      determine whether expression of apoptosis, proliferating cell nuclear antigen
      (PCNA), and p53 differ between an alkylating agent and a polycyclic aromatic
      hydrocarbon, host response was measured through sequential immunohistochemical
      detection of apoptosis (terminal deoxynucleotidyl transferase-mediated dUTP nick
      end-labeling method), PCNA PC-10, and p53 (PAb 240) in livers of the fish
      Fundulus grandis. Nine hundred fish were randomly assigned to 3 groups of 300
      fish each and kept in separate aquarium tanks. One group of fish was exposed to
      6.7 microM N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1 group was exposed to
      6.9 mM 2-aminofluorene (2-AF), and the remaining group served as a control. A
      significant decrease (p = 0.005) in the level of apoptosis and a significant
      increase (p < 0.0001) in the level of p53 were found on experimental day 180 in
      the livers of MNNG-exposed fish. PCNA was significantly increased (p < 0.005) by
      day 9 of the experiment in both MNNG and 2-AF fish when compared with controls,
      but no significant differences existed between the 2 groups of treated fish.
      Response of fish liver cells to MNNG-mediated and 2-AF-mediated injury differs,
      at least initially, in the expression of p53, inhibition of apoptosis, and
      increased net cell proliferation. Concurrent use of a marker for cell death with
      a marker of proliferation greatly enhances the assessment of the effect of these
      compounds on liver cells.

PMID- 10930049
TI  - Carcinogenicity of chloral hydrate administered in drinking water to the male
      F344/N rat and male B6C3F1 mouse.
AB  - Male B6C3F1 mice and male F344/N rats were exposed to chloral hydrate (chloral)
      in the drinking water for 2 years. Rats: Measured chloral hydrate drinking water
      concentrations for the study were 0.12 g/L, 0.58 g/L, and 2.51 g/L chloral
      hydrate that yielded time-weighted mean daily doses (MDDs) of 7.4, 37.4, and
      162.6 mg/kg per day. Water consumptions, survival, body weights, and organ
      weights were not altered in any of the chloral hydrate treatments. Life-time
      exposures to chloral hydrate failed to increase the prevalence (percentage of
      animals with a tumor) or the multiplicity (tumors/animal) of hepatocellular
      neoplasia. Chloral hydrate did not increase the prevalence of neoplasia at any
      other organ site. Mice: Measured chloral hydrate drinking water concentrations
      for the study were 0.12 g/L, 0.58 g/L, and 1.28 g/L that gave MDDs of 13.5, 65.0,
      and 146.6 mg/kg per day. Water consumptions, survival, body and organ weights,
      were not altered from the control values by any of the chloral hydrate
      treatments. Enhanced neoplasia was observed only in the liver. Prevalence and
      multiplicity of hepatocellular carcinoma (HC) were increased only for the high
      dose group (84.4%; 0.72 HC/animal; p < or = 0.05). Values of 54.3%; 0.72
      HC/animal and 59%; 1.03 HC/animal were observed for the 13.5- and 65.0-mg/kg per
      day treatment groups. Prevalence and multiplicity for the control group were
      54.8%; 0.74 HC/animal. Hepatoadenoma (HA) prevalence and multiplicity were
      significantly increased (p < or = 0.05) at all chloral hydrate concentrations:
      43.5%; 0.65 HA/animal, 51.3%; 0.95 HA/animal and 50%; 0.72 HA/animal at 13.5,
      65.0, and 146.6 mg/kg per day chloral hydrate compared to 21.4%; 0.21 HA/animal
      in the untreated group. Altered foci of cells were evident in all doses tested in
      the mouse, but no significant differences were observed over the control values.
      Hepatocellular necrosis was minimal and did not exceed that seen in untreated
      rats and mice. Chloral hydrate exposure did not alter serum chemistry and
      hepatocyte proliferation in rats and mice or increase hepatic palmitoyl CoA
      oxidase in mice at any of the time periods monitored. It was concluded that
      chloral hydrate was carcinogenic (hepatocellular neoplasia) in the male mouse,
      but not in the rat, following a lifetime exposure in the drinking water. Based
      upon the increased HA and combined tumors at all chloral hydrate doses tested, a
      no observed adverse effect level was not determined.

PMID- 10930047
TI  - The prophylactic effects of natural water-soluble antioxidant from spinach and
      apocynin in a rabbit model of lipopolysaccharide-induced endotoxemia.
AB  - Radical-scavenging antioxidants, as part of the cellular defense system, function
      to inhibit the formation and propagation of free radicals and active oxygen
      species formation. In previous studies we demonstrated that endotoxin
      lipopolysaccharide (LPS) promotes oxidative stress and associated pathological
      changes in a rat model and that use of selected antioxidants was effective in
      reducing LPS-related lipid peroxidation product formation in the liver, as well
      as LPS-related pathological changes in different organs. In this study, several
      toxicological parameters (ie, clinical signs, blood chemistry, and
      histopathological changes) were compared among groups of male New Zealand rabbits
      injected with LPS following prophylactic pretreatment with either of 2
      antioxidants, a group injected with LPS without pretreatment with antioxidants,
      groups injected with either of the 2 antioxidants only, and an untreated control
      group. The antioxidants used were a water-soluble natural antioxidant (NAO) from
      spinach and the NADPH oxidase inhibitor, apocynin. Exposure to LPS alone was
      associated clinically with depression, tachypnea, outer ear vasodilation, and
      iris congestion; biochemically with a significant increase in blood total
      bilirubin, transaminase activity, and glucose, total cholesterol, and
      triglyceride levels; macroscopically with multiple whitish areas in the liver;
      and histologically with hepatocellular focal necrosis and acute inflammation,
      thymic and splenic lymphoid necrosis and depletion, acute uveitis and hemorrhages
      in the ciliary processes, and decreased adrenal cortical cytoplasmic vacuolation
      considered consistent with depletion of steroidal hormone contents. The NAO had
      more effective prophylactic capacities than the apocynin. The protective effects
      were obvious in all investigated parameters. The results indicate the possible
      therapeutic efficacy of NAO in the treatment of clinical endotoxemia associated
      with gram-negative bacterial sepsis that is known to be associated with oxidative
      stress.

PMID- 10930050
TI  - Accumulation of iron in the rat lung after tracheal instillation of diesel
      particles.
AB  - Oxidant generation catalyzed by metals has been postulated to account for a lung
      injury following exposure to air pollution particles. In particles that are
      predominantly carbonaceous, it is difficult to implicate such an oxidative stress
      as the responsible mechanism, since concentrations of metals can be extremely
      low. Comparable to these air pollution particles, mineral oxide particles can
      include only minute amounts of metal, but lung injury following their exposure
      can be associated with an accumulation of endogenous iron from the host and an
      oxidative stress. We tested the hypothesis that diesel exhaust particulate (DEP)
      effects an accumulation of biologically active iron in the rat lung, with both
      oxidative stress and a lung injury resulting. Characterization of the DEP
      confirmed a high concentration of carbon, whereas metals were low in quantity.
      The concentration of total lavage iron in animals instilled with saline was low,
      but this concentration increased with exposure to DEP. Non-heme iron in lung
      tissue was similarly elevated after instillation of the diesel product. Particle
      instillation was associated with a decrease in lavage ascorbate concentration
      supporting an oxidative stress. Relative to saline exposure, DEP resulted in
      elevated lavage concentrations of the inflammatory mediators macrophage
      inflammatory protein-2 and tumor necrosis factor. Finally, an injury after
      particle instillation was evident with increased neutrophils and an elevation of
      lavage protein and lactic dehydrogenase. We conclude that DEP exposure effected
      an accumulation of iron in the rat lung. This accrual of iron was associated with
      an oxidative stress, release of oxidant-sensitive mediators, and a neutrophilic
      lung injury.

PMID- 10930051
TI  - Pathology and tissue sampling protocols for rodent carcinogenicity studies: time
      for revision.

PMID- 10930052
TI  - Safety and efficacy of meso-2,3-dimercaptosuccinic acid (DMSA) in children with
      elevated blood lead concentrations.
AB  - OBJECTIVE: To evaluate the safety and efficacy of meso-2,3-dimercaptosuccinic
      acid in the treatment of children with lead toxicity. DESIGN: This was an open
      label study in 59 children 12-65-months old, with pretreatment whole-blood lead
      levels of 25-66 microg/dL, who received 116, 26-28 day courses of oral dimer
      captosuccinic acid, while residing either in the Pediatric Clinical Research Unit
      of the Johns Hopkins Hospital or in lead-safe housing during the outpatient
      portion of the study. RESULTS: All, who completed the study, showed sharp
      decreases in blood lead concentration during therapy, but 2-3 weeks following
      completion of drug therapy, blood lead concentration rebounded to an average of
      58% (23 microg Pb/dL of whole blood) of their average pretreatment blood lead
      concentration (40 microg Pb/dL of whole blood). There were no adverse reactions
      attributable to dimercaptosuccinic acid; however, 2 of the 59 patients were
      reexposed to defective lead paint and experienced sharp increases in blood lead
      concentration while on therapy. In one instance, the child's blood lead
      concentration increased from 20 to 90 microg Pb/dL whole blood in 1 week. Other
      unexpected events were discussed in the text. CONCLUSIONS: Dimercaptosuccinic
      acid is apparently safe and does mobilize lead into the urine, but not the
      essential metals, zinc and copper. Reexposure is always a danger; therefore, all
      children, while on therapy, should be monitored for their blood lead
      concentration at weekly intervals during and immediately after therapy. No
      conclusions can be drawn from this study regarding long-term beneficial effects,
      if any, of this drug on late neurocognitive outcome.

PMID- 10930053
TI  - Distribution of lead and transthyretin in human eyes.
AB  - BACKGROUND: The retinal pigment epithelium serves as a defensive barrier to the
      retina in the same way that the choroid plexus functions in the brain. Previous
      studies have shown that lead sequestration in the choroid plexus reduces the
      production and secretion of transthyretin by the choroid plexus. The purpose of
      this study was to investigate the distribution of lead and transthyretin in human
      eyes and to explore the potential effect of lead on transthyretin in human eyes.
      METHODS: Eight pairs of human eyes were obtained from the New York City Eyebank
      within 24 hours of postmortem. The eyes were dissected to obtain the aqueous,
      vitreous, retina, and choroid. Lead and transthyretin concentrations in ocular
      tissues and liquids were determined by atomic absorption spectrophotometry for
      lead and radioimmunoassay for transthyretin. Lead accumulated in the retina at
      concentrations that were 166, 739, and 5 times higher than those in the aqueous,
      vitreous, and choroid, respectively (p < 0.05 for all comparisons). Lead
      concentrations in ocular tissues or intraocular liquids did not change as a
      function of age or gender. The concentration of transthyretin in the vitreous
      (14.4 +/- 5.1 SE microg/mL) was twice as much as in the aqueous (7.0 +/- 1.1SE
      microg/mL) and was significantly correlated to that in the retina (r = 0.93, p <
      0.005). CONCLUSIONS: This study indicates that lead accumulates in human ocular
      tissues, particularly in the retina. The markedly elevated retina lead level and
      its relationship to ocular transthyretin and other macromolecules bear further
      investigation.

PMID- 10930054
TI  - Evidence of enhanced iron excretion during systemic phosphorothioate
      oligodeoxynucleotide treatment.
AB  - BACKGROUND: Phosphorothioate oligonucleotides, in general, possess properties
      that could be utilized in the development of therapeutic heavy metal chelators.
      METHODS: Iron excretion was measured in 16 patients participating in studies to
      test the safety of OL(1)p53, a 20-mer phosphorothioate oligonucleotide
      complementary to p53 mRNA. Patients were given OL(1)p53 at doses of 0.05 to 0.25
      mg/kg/h for 10 days by continuous intravenous infusion. Urine was collected
      during the study and analyzed for iron, copper, cadmium, and zinc. RESULTS: We
      found that phosphorothioate oligonucleotides have a high affinity for iron as
      well as several other clinically relevant toxic metals. Analysis of patient urine
      following administration of OL(1)p53 reveals a 7.5-fold increase in iron
      excretion at low doses (0.05 mg/kg/h). CONCLUSIONS: Phosphorothioate
      oligonucleotides may have therapeutic potential as heavy metal chelators. Low
      doses of phosphorothioate oligonucleotide facilitated the excretion of iron.
      Renal clearance of iron-phosphorothioate oligonucleotide complexes most likely
      involves secretion into proximal tubules.

PMID- 10930055
TI  - Efficacy of the cation exchange resin, sodium polystyrene sulfonate, to decrease
      iron absorption.
AB  - BACKGROUND: Iron is not bound by charcoal; therefore, a method of binding iron in
      the gastrointestinal tract to prevent absorption in iron overdose is needed. This
      study investigated the efficacy and safety of sodium polystyrene sulfonate to
      prevent absorption of iron in human volunteers. METHODS: Six adult volunteers
      completed this prospective crossover trial. Following an oral dose of elemental
      iron 10 mg/kg, each subject received sodium polystyrene sulfonate 30 g or water
      as control. Baseline and serial serum iron samples were drawn to determine
      pharmacokinetic parameters. RESULTS: A trend toward increased time to peak
      following sodium polystyrene sulfonate compared to the control arm (5.7 vs 3.6
      hours) was observed but was not statistically significant (p = 0.517). A trend
      toward smaller area-under-the-curve for the sodium polystyrene sulfonate was
      evident but was not statistically significant (p = 0.77). Iron concentration
      increased on average 298 mcg/dL and 370 mcg/dL above baseline in the treatment
      and control arms (p = 0.44). Sodium polystyrene sulfonate is not an effective
      method of decontamination for iron overdose.

PMID- 10930056
TI  - Hepatic damage caused by chronic arsenic toxicity in experimental animals.
AB  - OBJECTIVE: Noncirrhotic fibrosis of the liver is common in subjects chronically
      consuming ground water geologically contaminated with arsenic, but the mechanism
      of the hepatic fibrosis is not known. Because lipid peroxidation has been
      implicated in the development of several other forms of hepatic fibrosis,
      including iron and copper overload, we have explored the roles of oxidative
      stress and lipid peroxidation in the causation of hepatic fibrosis in a murine
      model of chronic arsenic toxicity. METHODS: Male BALB/c mice were given drinking
      water contaminated with arsenic (3.2 mg/L) or arsenic-free (<0.01 mg/L, control)
      ad libitum. Mice were sacrificed at 3, 6, 9, 12, and 15 months for examination of
      hepatic histology and assays of hepatic reduced glutathione content, lipid
      peroxidation, enzymes of the antioxidant defense system, and membrane-bound
      sodium/potassium ATPase (Na+/K+ ATPase). RESULTS: After 12 months of arsenic
      feeding, the liver weights increased significantly as did serum aspartate
      aminotransferase and alanine aminotransferase. After 6 months of arsenic feeding,
      hepatic glutathione and the enzymes glucose-6-phosphate dehydrogenase and
      glutathione peroxidase were significantly lower than those of the control group.
      Hepatic catalase activity was significantly reduced at 9 months in the arsenic
      fed group, while glutathione-S-transferase and glutathione reductase activities
      were also significantly reduced at 12 and 15 months. Plasma membrane Na+/K+
      ATPase activity was reduced after 6 months while lipid peroxidation increased
      significantly after 6 months of arsenic feeding. Liver histology remained normal
      for the first 9 months, but showed fatty infiltration after 12 months of arsenic
      feeding. Histologic evidence of fibrosis was observed after 15 months.
      CONCLUSION: We have demonstrated hepatic fibrosis due to long-term arsenic
      toxicity in an animal model. Initial biochemical evidence of hepatic membrane
      damage, probably due to reduction of glutathione and antioxidant enzymes, may be
      seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum
      aminotransferase and alanine aminotransferase elevated at 12 months and hepatic
      fibrosis at 15 months. The murine model is proposed as relevant to epidemic human
      toxicity in areas of arsenic contamination.

PMID- 10930057
TI  - Cadmium hepatotoxicity and alterations of the mitochondrial function.
AB  - OBJECTIVE: To examine the effect of low concentrations of cadmium on isolated
      liver mitochondrial function as related to hepatotoxicity. METHODS: Tetraphenyl
      phosphonium ion uptake and retention, estimated with a tetraphenyl phosphonium
      sensitive electrode, was used to monitor changes in liver inner mitochondrial
      membrane potential. Ca2+ efflux was measured spectrophotometrically with the Ca2+
      indicator Arsenazo III. Mitochondrial swelling was measured
      spectrophotometrically at 540 nm. Oxygen consumption was measured with a Clark
      type oxygen microelectrode. RESULTS: Incubation of isolated liver mitochondria
      with cadmium (5-30 microM) altered mitochondrial function as indicated by
      swelling, inhibition of respiration, loss of inner mitochondrial membrane
      potential, and loss of preaccumulated Ca2+. The presence of dithiothreitol (2 mM)
      in the incubation medium restored mitochondrial function to almost the control
      level. Cyclosporin A (1 microM), however, did not provide any protection against
      cadmium toxicity. CONCLUSIONS: The findings point to a direct effect of cadmium
      on liver mitochondrial function. Cadmium toxicity may be due to loss of reduced
      glutathione rather than to increased mitochondrial inner membrane permeability.
      The effect of cadmium on liver mitochondria seems to be an early event in cadmium
      induced hepatotoxicity.

PMID- 10930058
TI  - Forensic toxicology in urban South Africa.
AB  - BACKGROUND: An analysis has been made of the pattern of deaths due to poisoning
      in South Africa over the period 1991-1996. METHODS: The database held by the
      Forensic Science Service Laboratory, covering the period 1991-1996 was analyzed.
      RESULTS: Agricultural chemicals are a major cause of mortality. Among drugs of
      abuse, combinations of methaqualone/diphenhydramine and cyclizine/dipipanone
      contribute a disproportionately high percentage of cases. Metal poisoning is
      common as are cases of poisoning attributed to remedies prescribed by traditional
      healers.

PMID- 10930059
TI  - The effect of sodium bicarbonate on propranolol-induced cardiovascular toxicity
      in a canine model.
AB  - STUDY OBJECTIVE: To evaluate the potential utility of sodium bicarbonate in an
      established model of acute propranolol toxicity. METHODS: Two minutes after the
      completion of a propranolol infusion (10 mg/kg), a bolus of 1.5 mEq/kg of sodium
      bicarbonate solution (1 mEq/mL) followed by an infusion of 1.5 mEq/kg over the
      next 26 minutes (n = 6) or an equivalent timing and volume of 5% dextrose
      solution (n = 6) was administered in each dog. Targeted cardiovascular parameters
      included heart rate, mean arterial pressure, left ventricular dP/dtmax, and QRS
      interval. RESULTS: Propranolol infusion significantly depressed heart rate (p <
      0.0001), mean arterial pressure (p < 0.0001), dP/dtmax (p < 0.0001) and prolonged
      the QRS interval (p < 0.0001). Sodium bicarbonate failed to significantly improve
      these targeted parameters when compared to control animals. CONCLUSION: In this
      canine model of propranolol toxicity, intravenous sodium bicarbonate appears to
      be an ineffective single therapy. Furthermore, these results may suggest a
      different mechanism of sodium channel blockade for propanolol than that of type
      IA antiarrhythmic agents.

PMID- 10930060
TI  - Dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate poisoning
      manifest as acute psychosis and pulmonary edema: treatment with hemoperfusion.
AB  - CASE REPORT: A 27-year-old man, employed by a synthetic fiber company, had been
      exposed to dimethylacetamide, ethylenediamine, and diphenylmethane diisocyanate
      in a confined space continuously for 4-6 hours per day for 3 days before
      admission. Hallucinations and delusions were noted at admission; pulmonary edema
      developed subsequently. The electroencephalogram showed diffuse moderate cortical
      dysfunction and slow waves at 4-7 Hz, 20-80 microV. Seizures, liver injury, and
      rhabdomyolysis were noted on the 4th hospital day. The patient was treated by
      hemoperfusion with a decrease in urine dimethylacetamide from 3,265 mg/g to 4
      mg/g creatinine over 4 days. Serial urinary dimethylacetamide and
      electroencephalogram correlated with the clinical condition.

PMID- 10930061
TI  - Acute elevation of blood lead levels within hours of ingestion of large
      quantities of lead shot.
AB  - BACKGROUND: Ingestion of elemental lead foreign bodies is felt to have a low risk
      of clinically significant lead absorption unless gastrointestinal pathology
      and/or prolonged transit time are present. We present a case of ingestion of a
      large quantity of small diameter lead shot accompanied by rapid elevation of
      blood lead levels. CASE REPORT: A 5 1/2-year-old previously healthy girl was
      found eating the pellets from an ankle weight. She vomited and complained of
      abdominal pain. In the emergency department, she had no complaints and normal
      vital signs. An abdominal X-ray showed thousands of small, round, metallic
      density objects in the stomach. Her white blood cell count was 14,700/mm3, and
      the hemoglobin, mean corpuscular volume, free erythrocyte protoporphyrin, zinc
      protoporphyrin, biochemistry panel 21, and urinalysis were normal. She had no
      prior lead level for comparison. Whole-bowel irrigation was begun and she passed
      over 11 stools with pellets as well as other foreign bodies (erasers, bead, etc.)
      in the first 24 hours. Pellets were still seen on X-ray the following day so she
      received a high-fiber diet and bisacodyl tablets 10 mg/d. On hospital day 2, her
      admission blood lead (drawn 13 hours after ingestion) was reported as 57
      microg/dL (2.7 microm/L) and chelation was begun with oral 2,3-dimercaptosuccinic
      acid 10 mg/kg 3x/d for 5 days, then 2x/d for 14 days. Her peak measured lead
      level was 79 microg/dL approximately 36 hours after ingestion. She excreted 2,273
      microg lead in the urine during her first 24 hours of chelation. Her blood lead
      dropped to 14.3 microg/dL by the end of chelation. She did not develop any
      apparent signs of lead poisoning. CONCLUSION: Acute elevations of blood lead
      concentrations may occur rapidly after ingestion of multiple small elemental lead
      objects.

PMID- 10930062
TI  - Subcutaneous injection of elemental mercury with distant skin lesions.
AB  - BACKGROUND: Mercury poisoning presents a variety of clinical pictures depending
      on chemical structure, amount absorbed, total mercury burden, and individual
      factors. Distant skin lesions, after subcutaneous injection of metallic mercury,
      have not been previously described. CASE REPORT: We present a homicidal,
      subcutaneous injection of mercury resulting in widespread skin lesions, remote
      from the radiologically visible mercury. The lesions appeared at 40 days and
      began to clear at 6 months after the injection.

PMID- 10930063
TI  - Ethylene glycol ingestion resulting in brainstem and midbrain dysfunction.
AB  - INTRODUCTION: Ethylene glycol toxicity has produced central nervous system
      abnormalities including coma, cerebral edema, and cranial nerve dysfunction. CASE
      REPORT: A 26-year-old male developed widespread brainstem and midbrain
      dysfunction with corresponding cranial computed tomography findings after
      ingesting ethylene glycol. The computed tomography scan which was obtained 3 days
      after ethylene glycol ingestion showed low density areas in the basal ganglia,
      thalami, midbrain, and upper pons. The neurologic findings in our patient
      reflected dysfunction of all the areas of hypodensity on the cranial computed
      tomography scan. A magnetic resonance imaging of the brain obtained 24 days after
      ingestion revealed bilateral putamen necrosis. The patient's neurologic sequelae
      resolved over the following 4 months.

PMID- 10930064
TI  - A depressed myocardium.
AB  - BACKGROUND: Venlafaxine is a potent neuronal serotonin and noradrenaline re
      uptake inhibitor, and to a lesser extent an inhibitor of dopamine reuptake.
      Paroxetine is a potent selective inhibitor of serotonin reuptake. CASE REPORT: A
      27-year-old man ingested 1987.5 mg of venlafaxine and 360 mg of paroxetine. He
      subsequently developed systolic and diastolic hypertension, transient
      electrocardiographic abnormalities, and an area of persistent myocardial damage.
      He recovered from his overdose with his blood pressure and electrocardiogram
      returning to normal. The area of myocardial damage was documented on
      echocardiogram as an area of marked hypokinesia at the basal anterior septum.
      Despite the absence of confirming blood levels or the absolute exclusion of
      cocaine, this case indicates that venlafaxine and paroxetine have the potential
      for serious cardiotoxicity when taken in overdose.

PMID- 10930065
TI  - Witchcraft or mycotoxin? The Salem witch trials.
AB  - BACKGROUND: The Salem witchcraft trials of 1692 have been studied by many
      historians looking for the complex social, political, and psychological
      determinants behind the community-wide hysteria that led to a travesty of justice
      and the deaths of 20 innocent Puritans. Recently, ergot poisoning has been put
      forth by some as a previously unsuspected cause of the bizarre behaviors of the
      young adolescent girls who accused the townsfolk of witchcraft. In this essay the
      circumstances behind the ergot poisoning theory for this historical event are
      described. When the evidence is weighed carefully both pro and con, it seems
      unlikely that ergotism explains much of what went on in colonial Salem.

PMID- 10930066
TI  - Toxwise.

PMID- 10930067
TI  - The role of cold-shock proteins in low-temperature adaptation of food-related
      bacteria.
AB  - There is a considerable interest in the cold adaptation of food-related bacteria,
      including starter cultures for industrial food fermentations, food spoilage
      bacteria and food-borne pathogens. Mechanisms that permit low-temperature growth
      involve cellular modifications for maintaining membrane fluidity, the uptake or
      synthesis of compatible solutes, the maintenance of the structural integrity of
      macromolecules and macromolecule assemblies, such as ribosomes and other
      components that affect gene expression. A specific cold response that is shared
      by nearly all food-related bacteria is the induction of the synthesis so-called
      cold-shock proteins (CSPs), which are small (7 kDa) proteins that are involved in
      mRNA folding, protein synthesis and/or freeze protection. In addition, CSPs are
      able to bind RNA and it is believed that these proteins act as RNA chaperones,
      thereby reducing the increased secondary folding of RNA at low temperatures. In
      this review established and novel aspects concerning the structure, function and
      control of these CSPs are discussed. A model for bacterial cold adaptation, with
      a central role for ribosomal functioning, and possible mechanisms for low
      temperature sensing are discussed.

PMID- 10930068
TI  - Propionicin SM1, a bacteriocin from Propionibacterium jensenii DF1: isolation and
      characterization of the protein and its gene.
AB  - We purified a bacteriocin from the cell-free supernatant of Propionibacterium
      jensenii DF1 isolated from Swiss raw milk, and named it propionicin SM1. The heat
      stable protein was strongly bactericidal against P. jensenii DSM20274. On the
      basis of the N-terminal amino acid sequence of the purified protein, a degenerate
      oligonucleotide probe was designed to locate and clone the corresponding gene of
      P. jensenii DF1. It hybridized exclusively with the DF1l-resident plasmid
      pLME106, but not with chromosomal DNA. Sequencing of the 6.9-kb plasmid revealed
      the targeted amino acid sequence within an open reading frame (ORF4) of 207 amino
      acids (molecular mass, 22,865 Da). The corresponding gene was named ppnA. It
      encodes the prepeptide PpnA that is processed to the mature protein (19,942 Da)
      propionicin SM1. No sequence homology is detectable with known proteins. However,
      the proposed leader peptide sequence containing 27 amino acids has typical signal
      peptide features and shows good homology to the leader peptide of Usp45, a
      protein excreted from Lactococcus lactis (VAN ASSELDONK et al., 1993). Plasmid
      pLME106 contains at least 9 ORFs, some exhibiting significant homologies to
      plasmid-encoded functions from other bacteria. The highest identity values were
      found for ORF1 with the theta replicase (acc. no. U39878) of Brevibacterium
      linens (58.8%) and ORF6 with the recombinase/invertase (acc. no. AF060871) found
      in Rhodococcus rhodochrous (46.4%).

PMID- 10930069
TI  - Occurrence and taxonomic significance of oxo-fatty acids in lipopolysaccharides
      from members of Mesorhizobium.
AB  - Lipopolysaccharides (LPSs) isolated from seven strains of Mesorhizobium were
      studied for the presence of fatty acids with particular attention for 27
      oxooctacosanoic acid and 4-oxo fatty acids. The LPSs from all analysed strains
      contained various amounts of 27-oxo-28:0 and all of them, with the exception of
      Mesorhizobium tianshanense, contained also 4-oxo fatty acids (4-oxo-20:0, 4-oxo-i
      21:0, 4-oxo-22:0). The group of amide-linked fatty acids consisted of a wide
      range of 3-hydroxylated and 4-oxo fatty acids whereas all the nonpolar as well as
      the (omega-1) hydroxylated long-chain acids and the 27-oxo-28:0 fatty acids were
      ester-linked. The characteristic spectrum of 3-hydroxy fatty acids and presence
      of 27-OH-28:0 as well as 27-oxo-28:0 acid in LPSs of Mesorhizobium showed that
      these strains were closely related. Therefore the lipid A fatty acid pattern
      could be a useful chemotaxonomic marker which helps to isolate the Mesorhizobium
      group from rhizobium bacteria during the classification process.

PMID- 10930070
TI  - Co-occurrence of non-toxic (cyanopeptolin) and toxic (microcystin) peptides in a
      bloom of Microcystis sp. from a Chilean lake.
AB  - A cyanobacterial bloom occurring in 1998 in lake Tres Pascualas
      (Concepcion/Chile) was found to be dominated by Microcystis sp. The bloom
      contained both non-toxic (cyanopeptolin-type) and hepatotoxic (microcystin-type)
      peptides. Cyanopeptolin structure of the non-toxic peptides (called cyanopeptolin
      VW-1 and VW-2, respectively) was revealed by matrix assisted laser desorption
      ionization mass spectrometry (MALDI-TOF-MS) of whole cells, showing dominant
      molecular ions at m/z = 975 and m/z 995, respectively. On post source decay
      (PSD), both cyanopeptolins showed fragments deriving from Ahp-Phe-MTyr (3-amino-6
      hydroxy-2-piperidone), the characteristic partial structure of cyanopeptolins.
      The amounts of each of the two cyanopeptolins could only roughly be estimated to
      be >0.1% of bloom material dry weight. In addition the blooms contained
      microcystins (20 microg/g bloom dry weight as determined by RP-HPLC, 13 microg/g
      according to ELISA determination). MALDI-TOF-MS revealed several structural
      variants of microcystin: MCYST-RR (microcystin with Arg and Arg, indicated by m/z
      1,038 and confirmed by PSD revealing a m/z = 135 fragment deriving from the Adda
      side chain, MCYST-FR (microcystin with Phe and Arg, indicated by m/z = 1,015).
      The presence of [Asp(3)]-MCYST-LR (microcystin with Leu and Arg, Asp non
      methylated, indicated by m/z 981), and [Asp(3)]-MCYST-YR (microcystin with Tyr
      and Arg, Asp non-methylated, indicated by m/z 1,031) were likely. The relative
      amounts of the peptides varied between February, April, and May. Whole cell
      extracts from the bloom material revealed specific enzyme inhibitory activities.
      The serin-proteases trypsin, plasmin, elastase were inhibited, assumable due to
      the cyanopeptolins found. Elastase and the cysteine-protease papain were not
      inhibited, inhibitions of protein kinase and glutathione S-transferase (GST) were
      low. Strong inhibition was observed with protein-phosphatase-1, likely due to the
      microcystins present in the samples.

PMID- 10930071
TI  - Divergence of glyceraldehyde-3-phosphate dehydrogenase isozymes in Saccharomyces
      cerevisiae complex.
AB  - Although sake yeasts are placed in Saccharomyces cerevisiae, we have been
      interested in their difference from the other subgroups of the species, and
      examined their proteins. When SDS-PAGE patterns of their soluble proteins were
      compared, specific differences between subgroups were found in their 36,000 Da
      regions. Proteins isolated therefrom were found to be subunits of three isomers
      of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from their N-terminal amino
      acid sequences and identified with anti-GAPDH serum. Therefore, comparison of
      zymogram was carried out by a modified method: denatured monomers were observed
      and the enzyme activity of their oligomers was not considered. SDS-PAGE patterns
      of all the sake yeasts differed from those of the other strains of S. cerevisiae.
      Strains of Saccharomyces bayanus showed uniform patterns which are different from
      the above two groups. Saccharomyces pastorianus strains resembled S. bayanus and
      were partly similar to S. cerevisiae in their patterns, in agreement with the
      hypothesis that S. pastorianus is a hybrid between these two species. Patterns of
      S. paradoxus appeared to be rather similar to those of sake yeasts. Results on
      the other species of the genus and on the preliminary experiments on PAGE of
      native isozymes are also described.

PMID- 10930072
TI  - Taxonomic position of "Pseudomonas oxalaticus" strain ox14T (DSM 1105T) (Khambata
      and Bhat, 1953) and its description in the genus Ralstonia as Ralstonia oxalatica
      comb. nov.
AB  - "Pseudomonas oxalaticus" strain Ox1T (= DSM 1105T), which was described as an
      oxalate-decomposing bacterium, was reinvestigated to clarify its taxonomic
      position. 16S ribosomal DNA sequence comparisons demonstrated that this species
      is phylogenetically related to the species of the genus Ralstonia. and represents
      a new species. The result of the DNA-DNA hybridization value was supported in
      this placement. Strain Ox1T is closely related to Ralstonia eutropha with a less
      than 60% DNA-DNA hybridization value. The new name Ralstonia oxalatica comb. nov.
      is proposed to strain Ox1T, on the basis of these results and previously
      published data for the G+C content of the genomic DNA and the phenotypic
      characters.

PMID- 10930073
TI  - Methylopila helvetica sp. nov. and Methylobacterium dichloromethanicum sp. nov.-
      novel aerobic facultatively methylotrophic bacteria utilizing dichloromethane.
AB  - Eight strains of Gram-negative, aerobic, asporogenous, neutrophilic, mesophilic,
      facultatively methylotrophic bacteria are taxonomically described. These icl-
      serine pathway methylobacteria utilize dichloromethane, methanol and methylamine
      as well as a variety of polycarbon compounds as the carbon and energy source. The
      major cellular fatty acids of the non-pigmented strains DM1, DM3, and DM5 to DM9
      are C18:1, C16:0, C18:0, Ccy19:0 and that of the pink-pigmented strain DM4 is
      C18:1. The main quinone of all the strains is Q-10. The non-pigmented strains
      have similar phenotypic properties and a high level of DNA-DNA relatedness (81
      98%) as determined by hybridization. All strains belong to the alpha-subgroup of
      the alpha-Proteobacteria. 16S rDNA sequence analysis led to the classification of
      these dichloromethane-utilizers in the genus Methylopila as a new species -
      Methylopila helvetica sp.nov. with the type strain DM9 (=VKM B-2189). The pink
      pigmented strain DM4 belongs to the genus Methylobacterium but differs from the
      known members of this genus by some phenotypic properties, DNA-DNA relatedness
      (14-57%) and 16S rDNA sequence. Strain DM4 is named Methylobacterium
      dichloromethanicum sp. nov. (VKM B-2191 = DSMZ 6343).

PMID- 10930074
TI  - New LL-diaminopimelic acid-containing actinomycetes from hypersaline,
      heliothermal and meromictic Antarctic Ekho Lake: Nocardioides aquaticus sp. nov.
      and Friedmanniella [correction of Friedmannielly] lacustris sp. nov.
AB  - Two Gram-positive, non-motile and aerobic bacteria were isolated from a water
      sample of the hypersaline Ekho Lake, Antarctica. The cocci or short rods grew
      well on oligotrophic PYGV agar of pH 7.5 and at 26 degrees C. Strains EL-17KT and
      EL-17AT both required thiamine and biotin, strain EL-17AT also required nicotinic
      acid. Carbon sources utilized by both strains were acetate, pyruvate, alpha-D
      glucose, glutamate and (weakly) citrate, but succinate, malate or butyrate were
      utilized only by EL-17KT. Gelatin, starch and DNA were hydrolyzed, NH, was formed
      from peptone, and nitrate was reduced aerobically by both strains. The isolates
      had the same temperature tolerance for growth in the range tested (below 3 to
      above 33.5 degrees C) and pH range (<5.5 to >9.5) and were sensitive to
      chloramphenicol and penicillin G. Their cell walls contained LL-diaminopimelic
      acid and had a single glycine residue as interpeptide bridge. Strain EL-17AT
      contained glycine at position 1 of the peptide subunit (peptidoglycan type A
      3gamma'). Isolates EL-17KT and EL-17AT differed in their maximum NaCl tolerance,
      which was 15% or 6-8%, respectively. The major fatty acid of EL-17KT was C18:1
      and that of EL-17AT was ai-C15:0. The major respiratory quinones of EL-17KT and
      EL-17AT were MK-8(H4) and MK-9(H4), respectively. The former isolate had 69 mol%
      G+C, the latter had 73 mol% G+C. Comparative 16S rRNA gene sequencing revealed
      phylogenetic relationships of isolate EL-17KT with the genus Nocardioides, with
      N. pyridinolyticus and N. plantarum as the closest relatives. Phenotypic and
      genotypic characteristics support the description of a new species, Nocardioides
      aquaticus sp. nov., with EL-17KT as the type strain (= DSM 11439T). Isolate EL
      17AT is related to the genus Friedmanniella, with E antarctica and E spumicola as
      the closest relatives. The differentiating characteristics support the
      description of a new species, Friedmanniella lacustris sp. nov., with EL-17AT as
      the type strain (= DSM 11465T).

PMID- 10930075
TI  - Identification of enterococci at the species level by sequencing of the genes for
      D-alanine:D-alanine ligases.
AB  - A PCR assay based on the use of degenerate oligodeoxyribonucleotides allowed
      characterization of a fragment internal to the ddl genes encoding D-alanine:D
      alanine ligases in Enterococcus columbae, E. durans, E. malodoratus, E. mundtii,
      E. raffinosus, E. seriolicida, E. solitarius, and E. sulfureus. Phylogenetic
      analysis of the sequence of the amplification products and of those already
      obtained from E. aviuni, E. casseliflavus, E. cecorum, E. dispar, E. faecalis, E.
      faecium, E. flavescens, E. gallinarurm, E. hirae, E. pseudoavium, and E.
      saccharolvticus yielded an evolutionary tree with a topology similar to that
      based on 16S rRNA sequences. Partial sequencing of the ddl gene can therefore be
      used for genotypic identification of Enterococcus spp.

PMID- 10930076
TI  - Phylogenetic analysis of 23S rRNA gene sequences of. Agrobacterium, Rhizobium and
      Sinorhizobium strains.
AB  - The phylogenetic relationship among twelve Agrobacterium, four Rhizobium, and two
      Sinorhizobium strains originating from various host plants and geographical
      regions was studied by analysis of the 23S rDNA sequences. The study included
      Agrobacterium strains belonging to biovars 1, 2 (with tumor- or hairy-root
      inducing and non-pathogenic strains), A. vitis, A. rubi; representative species
      of the Rhizobium genus: R. galegae, R. leguminosarum and R. tropici and
      Sinorhizobium meliloti strains. The phylogenetic analysis showed that within
      Agrobacterium, the biovar designation was reflected in the 23S rDNA similarity
      and that strains of Agrobacterium and Rhizobium are closely related to each
      other. The results suggest that the taxonomic definition of Agrobacterium and
      Rhizobium should be considered for revision and that the Agrobacterium-biovar
      identity is probably a reliable taxonomic trait.

PMID- 10930077
TI  - Taxonomic study of "tufted mitior" strains of streptococci (Streptococcus
      sanguinis biotype 11); recognition of a new genospecies.
AB  - The taxonomic position of tufted strains of streptococci, phenotypically
      resembling Streptococcus mitis and previously referred to as 'tufted mitior' was
      investigated. By 16S rRNA sequence analysis, it was clear that the "tufted
      mitior" strains belonged to the mitis group of species within the genus
      Streptococcus. It was confirmed that these strains were taxonomically independent
      at the species level, sharing less than 43%, DNA-DNA similarity with all
      established species of the mitis group. However biochemical test data obtained,
      using three commercial identification kits (Rapid ID32 Strep, STREPTOGRAM, and
      Biolog GP-plate) together with in-house biochemical tests employing 4-MUF-linked
      fluorogenic substrates did not reveal sufficient differential tests with which to
      identify the "tufted mitior" strains unequivocally. From these data, we conclude
      that these "tufted mitior" strains represent a new taxon within the mitis group
      of the genus Streptococcus, and propose that they should be considered as a
      genospecies until differential phenotypic characteristics are found for their
      identification.

PMID- 10930078
TI  - Identification of lactobacillus delbrueckii and subspecies by hybridization
      probes and PCR.
AB  - Three methods addressing two different target sites were compared for
      identification and differentiation of the subspecies Lactobacillus delbrueckii
      subsp. bulgaricus and Lactobacillus delbrueckii subsp. lactis/delbrueckii. A PCR
      method - three primer pairs that enable direct identification of the species and
      the two subspecies, respectively - was derived from a DNA fragment showing
      significant similarities to parts of the addAB genes of Bacillus sutbtilis. In
      addition, two oligonucleotide probes for the two subspecies were designed from
      that DNA region. Further, two oligonucleotide probes targeting the 16S rDNA were
      developed for subspecies differentiation by a one base-pair difference following
      identification of the species. Moreover, these probes were demonstrated to be
      applicable for in situ hybridization experiments. The results obtained by the
      different methods were in good agreement.

PMID- 10930079
TI  - Monitoring and survival of Lactobacillus paracasei LTH 2579 in food and the human
      intestinal tract.
AB  - A PCR-based detection system specific for Lactobacillus paracasei LTH 2579 was
      developed and applied to follow the fate of the strain in complex ecosystems.
      This strain was isolated from fruit mash and was characterised as being highly
      resistant to low pH and bile at concentrations as they occur in the human
      digestive tract. The application of the subtraction hybridisation technique
      permitted to identify a 235 bp chromosomal DNA fragment of strain LTH 2579. Based
      on this target sequence a specific PCR system was developed and combined with the
      species-specific PCR system for L. paracasei. This combination of PCR based
      detection systems was successfully applied to monitor L. paracasei LTH 2579 in
      fermented sausages which were inoculated with this strain (2.0 x 10(7) CFU/g)
      together with the strongly competitive L. sakei LTH 681 (1.0 x 10(6) CFU/g). At
      the time of consumption of the sausages the respective counts were 1.8 x 10(7)
      and 1.4 x 10(8) CFU/g. After consumption of the sausages by three volunteers L.
      paracasei LTH 2579 was recovered from fecal samples. The counts determined for
      the strain ranged between 1.2 x 10(7) and 1.5 x 10(8) CFU/g of feces. The
      fortuitous lactobacilli constituted a share of 5-12% of the lactobacilli in the
      fecal flora.

PMID- 10930080
TI  - Molecular diversity of leuconostoc mesenteroides and leuconostoc citreum isolated
      from traditional french cheeses as revealed by RAPD fingerprinting, 16S rDNA
      sequencing and 16S rDNA fragment amplification.
AB  - For a long time, the identification of the Leuconostoc species has been limited
      by a lack of accurate biochemical and physiological tests. Here, we use a
      combination of RAPD, 16S rDNA sequencing, and 16S rDNA fragment amplification
      with specific primers to classify different leuconostocs at the species and
      strain level. We analysed the molecular diversity of a collection of 221 strains
      mainly isolated from traditional French cheeses. The majority of the strains were
      classified as Leuconostoc mesenteroides (83.7%) or Leuconostoc citreum (14%)
      using molecular techniques. Despite their presence in French cheeses, the role of
      L. citreum in traditional technologies has not been determined, probably because
      of the lack of strain identification criteria. Only one strain of Leuconostoc
      lactis and Leuconostoc fallax were identified in this collection, and no
      Weissella paramesenteroides strain was found. However, dextran negative variants
      of L. mesenteroides, phenotypically misclassified as W. paramesenteroides, were
      present. The molecular techniques used did not allow us to separate strains of
      the three L. mesenteroides subspecies (mesenteroides, dextranicum and cremoris).
      In accordance with previously published results, our findings suggest that these
      subspecies may be classified as biovars. Correlation found between phenotypes
      dextranicum and mesenteroides of L. mesenteroides and cheese technology
      characteristics suggests that certain strains may be better adapted to particular
      technological environments.

PMID- 10930081
TI  - Isolation and identification of tetracycline resistant lactic acid bacteria from
      pre-packed sliced meat products.
AB  - In recent years, the food chain has been recognised as one of the main routes for
      transmission of antibiotic resistant bacteria between the animal and human
      population. In this regard, the current study aimed to investigate if
      tetracycline resistant (tetR) lactic acid bacteria (LAB) are present in ready-to
      eat modified atmosphere packed (MAP) sliced meat products including fermented dry
      sausage, cooked chicken breast meat and cooked ham. From population graphs based
      on doubling tetracycline concentrations between 0 and 256 microg ml(-1), only
      fermented dry sausage was shown to contain a high-level retR LAB population
      (5.10(1) - 2,23.10(4) CFU/g), and this in four out of ten examined sausages. From
      these four positive sausages, a total of 100 strains were isolated on de Man,
      Rogosa and Sharpe-sorbic acid (MRS-S) agar without tetracycline (n = 45) and on
      MRS-S agar supplemented with a tetracycline breakpoint concentration of 64 microg
      ml(-1) (n = 55). Using resistance histograms derived from the disc diffusion
      method, all these strains were grouped as sensitive to rifampicin, erythromycin
      and ampicillin. All strains from the tetracycline-containing MRS-S plates were
      resistant to tetracycline. Identification with whole-cell protein profiling
      revealed that the total strain set represented four different species:
      Pediococcus pentosaceus, Lactobacillus plantarum, Lactobacillus sakei subsp.
      carnosus and Lactobacillus curvatus. All species are commonly associated with
      fermented dry sausage, either as starter culture or as natural contaminants. The
      latter three species were found to comprise all tetracycline resistant strains.
      To our knowledge, this is the first report providing evidence for the presence of
      tetR LAB in final ready-to-eat pre-packed fermented dry sausages.

PMID- 10930082
TI  - Molecular diversity of lactic acid bacteria from cassava sour starch (Colombia).
AB  - Lactic acid bacteria and more particularly lactobacilli and Leuconostoc, are
      widely found in a wide variety of traditional fermented foods of tropical
      countries, made with cereals, tubers, meat or fish. These products represent a
      source of bacterial diversity that cannot be accurately analysed using classical
      phenotypic and biochemical tests. In the present work, the identification and the
      molecular diversity of lactic acid bacteria isolated from cassava sour starch
      fermentation were assessed by using a combination of complementary molecular
      methods: Randomly Amplified Polymorphic DNA fingerprinting (RAPD), plasmid
      profiling, hybridization using rRNA phylogenetic probes and partial 16S rDNA
      sequencing. The results revealed a large diversity of bacterial species (Lb.
      manihotivorans, Lb. plantarum, Lb. casei, Lb. hilgardii, Lb. buchneri, Lb.
      fermentum, Ln. mesenteroides and Pediococcus sp.). However, the most frequently
      isolated species were Lb. plantarum and Lb. manihotivorans. The RAPD analysis
      revealed a large molecular diversity between Lb. manihotivorans or Lb. plantarum
      strains. These results, observed on a rather limited number of samples, reveal
      that significant bacterial diversity is generated in traditional cassava sour
      starch fermentations. We propose that the presence of the amylolytic Lb.
      manihotivorans strains could have a role in sour starch processing.

PMID- 10930083
TI  - Isolation and identification of cellulolytic bacteria involved in the degradation
      of natural cellulosic fibres.
AB  - In search for bacterial cultures that are able to rapidly degrade cellulosic
      plant fibres in vitro, 77 cellulolytic strains were isolated from Belgian and
      Czech soils after enrichment on flax or sisal fibres as sole sources of carbon.
      The strains were characterized using fatty acid analysis, and 74 strains were
      grouped into three major clusters by numerical analysis. The first major cluster
      contained Cellulomonas strains. Within this cluster three subclusters could be
      delineated by principal component analysis, that were recognized by their fatty
      acid compositions as Cellulomonas gelida, Cellulomonas biazotea and Cellulomonas
      cellulans, containing 9, 8 and 13 strains respectively. The second major cluster,
      with 9 strains, was assigned to Flavobacterium johnsoniae. The 34 strains of the
      third cluster could not be identified by commercial identification systems on the
      basis of their fatty acid profiles and API 20NE profiles. On the basis of their
      phenotypic characteristics they met the description of the genus Cellvibrio,
      their fatty acid profiles were similar to those of four authentic Cellvibrio
      mixtus strains, and the 16S rRNA genes from four representatives showed up to
      97.8% sequence similarity to 16S rDNA from Cellvibrio mixtus ACM 2603. Three non
      clustered strains were assigned to Curtobacterium flaccumfaciens, Achromobacter
      piechaudii and Pseudomonas mendocina. Two strains assigned to Cellvibrio were
      able to degrade several flax, broom and cotton fibres very rapidly in a
      standardized in vitro test, causing mass losses of 40 to 86% within 13 days of
      incubation, but not jute.

PMID- 10930084
TI  - Expression levels and patterns of glycolytic yeast genes during wine
      fermentation.
AB  - Promoters from glycolytic genes are widely used for gene overexpression in the
      yeast Saccharomyces cerevisiae. Wine strains are not an exception, and genes of
      enological interest have been expressed in this way. However, the transcriptional
      pattern of glycolytic genes has never been studied during wine fermentation. In
      this work we describe the levels and expression patterns of glycolytic genes for
      a wine yeast strain during the alcoholic fermentation of three different musts.
      Results show similar transcriptional patterns for all genes studied: maximal
      levels of mRNA at the exponential growth stage, and a gradual decrease during the
      stationary phase, in accordance with the fermentation rates. The glyceraldehyde 3
      phosphate dehydrogenase genes reach the highest transcriptional levels during
      wine fermentation, similarly as previously described for laboratory strains and
      conditions.

PMID- 10930085
TI  - Urokinase plasminogen activator system gene expression is increased in human
      breast carcinoma and its bone metastases--a comparison of normal breast tissue,
      non-invasive and invasive carcinoma and osseous metastases.
AB  - The urokinase plasminogen activator (uPA) system has been widely associated with
      the development of breast carcinoma. However, the role of the urokinase pathway
      in the development of osseous breast cancer metastases has been largely
      overlooked. We studied the expression of uPA, urokinase plasminogen activator
      receptor (uPAR)- and plasminogen activator inhibitor type-1 (PAI-1) in human
      breast carcinomas and their bone metastases, using in situ hybridisation. Studies
      were performed using paraffin-embedded tissue from 13 ductal carcinomas, 23
      invasive ductal carcinomas, five normal breasts and 25 bone metastases. The
      majority of the tumours examined expressed low to moderate levels of uPA mRNA and
      low to high levels of uPAR and PAI-1 mRNA, which was predominantly localised to
      the epithelial tumour cells. There was slight over-expression of uPA and PAI-1
      mRNA and a marked increase in uPAR mRNA expression in the malignant tumours
      compared with benign tissue. Overall, uPAR and PAI-1 mRNA expression was found to
      be more variable than uPA mRNA, suggesting a possible role of the receptor and
      inhibitor in the regulation of uPA activity. Increased alpha1(I) procollagen
      (COL) and osteopontin (OPN) mRNA expression was detected, primarily in the
      stromal cells, in malignant tumours compared with the benign tissue. The
      increased expression of the components of the uPA system on the epithelial tumour
      cells may account for the activation of the proteolytic cascade that occurs
      during breast cancer metastasis to bone. Furthermore, the over-expression of COL
      and OPN suggests a possible interaction between these matrix proteins and the uPA
      system.

PMID- 10930086
TI  - Enhancement of mdr1 gene expression in normal tissue adjacent to advanced breast
      cancer.
AB  - In the present study, mdr1 gene expression was investigated by a sensitive
      reverse transcriptase-PCR assay in advanced breast cancer and in corresponding
      adjacent normal tissues obtained before and after treatment with primary
      chemotherapy. Comparatively to normal tissues, a significant induction of mdr1
      expression was observed in untreated tumors (p = 0.0222). Similarly, a
      significant induction of mdr1 expression was revealed when treated samples were
      compared to untreated counterparts (p = 0.0222), but no differences were detected
      between tumor and normal samples (p = 0.3199). Noteworthy, a significant
      induction of mdr1 gene expression occurred in treated normal samples
      comparatively to untreated ones (p = 0.0037), and this induction was even more
      important in normal than in tumoral tissue (p = 0.0627). However, neither the
      basal expression nor the induction of mdr1 were correlated with subsequent
      response to chemotherapy or with survival. Thus, in agreement with previous
      reports, our data show that chemotherapy induce mdr1 gene expression in breast
      cancer cells, but they also indicate that a similar phenomenon occurs in adjacent
      normal tissues. Therefore, our results strongly suggest that mdr1 gene
      overexpression is not a characteristic of breast malignant cells, but rather
      constitutes a general phenomenon occurring both in normal and tumor cells which
      could explain at least in part the absence of relationship between mdr1
      expression and the clinical outcome of breast cancer patients.

PMID- 10930087
TI  - Somatostatin receptor in breast cancer and axillary nodes: study with
      scintigraphy, histopathology and receptor autoradiography.
AB  - We conducted a prospective analysis of somatostatin receptor scintigraphy using
      (111)In radiolabeled pentetreotide, a somatostatin analog, in patients with
      breast cancer in the aim to visualize the primary tumor and axillary or
      parasternal metastatic extension because some malignant breast tumors express
      somatostatin receptors (SS-R) in 50%, approximately. An analysis of SS-R was
      performed by autoradiography. PATIENTS AND METHODS: Thirteen patients with
      clinically suspected breast tumors (T1, T2), and at least one palpable axillary
      node (N1) were included. In vivo planar scintigrams were acquired 1, 4, and 24 h
      after subcutaneous, then after intravenous injections (24 h delay between
      injections). Improved (111)In-pentetreotide uptake in invaded nodes after
      subcutaneous injection was hypothesized. Ex vivo scintigrams of surgical
      specimens were also acquired immediately after tumor resection and axillary
      dissection. Pathological examination and receptor autoradiography were performed
      on all surgical specimens. RESULTS: Among 11 pathologically proven malignant
      tumors (9 ductal and 2 lobular carcinomas), only four were scintigraphically
      visible although six expressed SS-R receptors in vitro. Among six pathologically
      proven malignant nodes, four expressed SS-R, including two visualized
      scintigraphically. Scintigrams acquired after subcutaneous injections were less
      sensitive than after intravenous injections. There were no false positive. False
      negatives occurred in cases with small tumors with low-density or heterogeneously
      distributed SS-R. There was no significant difference by histological type or
      prognostic factors. CONCLUSION: Somatostatin receptor scintigraphy does not
      appear to be sensitive enough to evaluate axillary node extension of breast
      cancer or even to confirm the presence of tumoral tissue, and this whatever the
      administration route for (111)In-pentetreotide.

PMID- 10930088
TI  - p(21WAF1/CIP1) expression in breast cancers: associations with p53 and outcome.
AB  - p21(WAF1/CIP1) is transcriptionally activated by wt p53 and inhibits G1
      associated cyclins, a major mechanism by which p53 inhibits cellular
      proliferation. Archival breast cancers (798) with a median follow-up of 16.3
      years were used to explore the prognostic value of p21 immunohistochemical
      analyses. p21 immunostaining was detected in the majority (726/798: 91%) of
      breast cancers as well as adjacent in situ carcinomas (125/170: 74%),
      hyperplastic lesions (140/349: 40%) and normal breast epithelium adjacent to
      carcinoma (3/89: 3%). Complete immunonegativity was observed in only 9% of
      invasive cancers and was associated with p53 immunopositivity (p < 0.05).
      Univariate analysis of all patients showed that p21 negativity was associated
      with a longer disease specific survival (relative risk (RR) 1.5). Node positive
      p21- patients also showed a longer disease free and disease specific survival as
      compared to tumor p21+ patients. In node negative patients, p53 positivity but
      not p21 alone, was significantly associated with a shortened disease free
      survival (RR = 1.6). Node negative patients who were p53+ p21-, in particular had
      the shortest disease free survival compared to other p53, p21 subgroups (i.e.,
      p21 negativity was associated with a worse outcome). Multivariate analysis of
      lymph node negative patients (n > 300) demonstrated that tumor size and tumor
      grade were independently predictive of outcome, whereas neither p53 nor p21 were
      significant. For node positive patients, p21 positivity (p = 0.05), p53
      positivity (p = 0.03), a higher number of positive nodes, larger tumor size,
      steroid receptor negativity, high proliferation rate, and erbB-2 expression were
      each independently associated with poor outcome. In summary, p21 negativity was
      inversely correlated with p53 immunopositivity in the majority of cases. p21
      negative tumor patients had an improved outcome if they were node positive,
      whereas p21 status was not significantly associated with survival in node
      negative patients. This observation may be due to the reported 'uncoupling of S
      phase and mitosis' associated with a loss of p21 expression which may result in
      enhanced sensitivity to chemotherapy.

PMID- 10930089
TI  - Sex hormone-induced mammary carcinogenesis in the female Noble rats: expression
      of bcl-2 and bax in hormonal mammary carcinogenesis.
AB  - We have established a Noble rat model to explore the mechanisms of hormonal
      mammary carcinogenesis, in which the role of androgen in promoting mammary
      carcinogenesis was highlighted. We have also established that stromal-epithelial
      interactions may be responsible for the promotional effects of testosterone in
      mammary carcinogenesis. Based on these understandings, in the present study we
      examined the expression of Bcl-2 and Bax in pre-malignant mammary glands from
      rats treated with different protocols of sex hormones for 7 weeks as well as sex
      hormone induced mammary tumours. We observed that Bcl-2 was strongly expressed in
      most of mammary tumour cells, whereas weak or negative in adjacent normal or
      hyperplastic ductal structures. On the contrary, Bax immunoreactivity was weak in
      mammary tumour cells while strongly expressed in adjacent normal or hyperplastic
      ductal structures. More importantly, the results from comparative study of 'pre
      malignant' glands further showed that when animals were treated with 17beta
      oestradiol, the mammary epithelial cells expressed high levels of Bcl-2. The
      results from rats treated with testosterone, either alone or in combination with
      oestrogen, give rise to high levels of Bax expression in 'pre-malignant' mammary
      glands. These observations indicate that in 'pre-malignant' mammary glands,
      treatment with testosterone, either alone or in combination with 17beta
      oestradiol, may induce high apoptotic activities. However, in fully developed
      mammary tumours, the apoptotic activities apparently decrease in tumour cells.
      TUNEL assay provides further data to support this conclusion. Our study, thus,
      suggests that androgens may play a promoting role in mammary carcinogenesis by
      upregulation of Bax expression and induction of high apoptotic activities in 'pre
      malignant' stage, which would provide a selective pressure favouring the
      expansion of the initiated cells.

PMID- 10930090
TI  - Protein production by osteoblasts: modulation by breast cancer cell-derived
      factors.
AB  - Breast cancer cells (BCC) frequently metastasize to bone where they may cause
      tumor-induced osteolysis (TIO). While the important eroding role of the
      osteoclasts in TIO is well admitted, the possibility that BCC and/or osteoblasts
      activated by tumoral factors could also directly degrade bone matrix in this
      pathology has been much less investigated. We show here that the net collagen
      amount produced in vitro by normal human osteoblasts and osteoblast-like cells
      was significantly reduced by culture medium conditioned by several BCC lines,
      including three newly isolated ones. There was no evidence for a decrease in
      collagen synthesis, as assessed by the production of the carboxyterminal
      propeptide of type I collagen. In contrast, the effect of BCC-derived medium on
      collagen amount was attenuated by inhibitors of matrix metalloproteinases (MMPs)
      as well as by tranexamic acid, an inhibitor of the plasminogen conversion to
      plasmin, while it was abolished in presence of the two kinds of proteinase
      inhibitors. This osteoblastic protein degradation activity appeared to be
      attributable to factors secreted by the osteoblasts as well as by BCC. These
      factors had molecular weights lower as well as higher than 10 kD. Our data
      suggest that besides the eroding action of osteoclasts, BCC- and osteoblast
      derived MMPs and serine proteinases might play a direct role in bone collagen
      degradation in TIO.

PMID- 10930091
TI  - Ectopic expression of Rsu-1 results in elevation of p21CIP and inhibits anchorage
      independent growth of MCF7 breast cancer cells.
AB  - Signal transduction from tyrosine kinase receptors mediates growth regulation of
      breast cancer cells in part through the GTPase Ras and downstream kinases. Rsu-1
      is a cDNA previously identified as an inhibitor of Ras-induced transformation. An
      HA-epitope tagged Rsu-1 cDNA was introduced into the MCF7 breast carcinoma cell
      line. Stable transfectants were selected and used for analysis of Rsu-1
      expression on growth control and Ras-dependent kinase pathways. Assessment of
      biological activity of HA-Rsu-1 transfectants revealed that HA-Rsu-1 clones
      showed slower anchorage dependent growth rates than control MCF7 cell lines and a
      significant reduction in anchorage independent growth. Analysis of cell cycle
      regulatory proteins required for transit through G1 revealed that HA-Rsu-1
      transfectant cell lines expressed elevated levels of p21CIP CDK inhibitor.
      Perturbations in signal transduction pathways which can be activated by Ras were
      detected in the Ha-Rsu-1 transfectants. Exposure of serum-starved cells to EGF
      revealed that expression of HA-Rsu-1 increased ERK-2 kinase activation, decreased
      activation of Jun kinase and inhibited Rho-dependent Rho-alpha kinase (ROK)
      activity compared to control cells. While serum starvation reduced AKT activity
      to undetectable levels in HA-Rsu-1 transfectants but not in control MCF7 cells,
      activation of AKT kinase by serum was unaffected by HA-Rsu-1 expression. Finally,
      the level of c-myc transcription in HA-Rsu-1 transfectants reached only 60% of
      the MCF7 control cell line following serum stimulation of starved cells while Fos
      RNA levels were similar to control cells. These results demonstrate that
      increased Rsu-1 expression critically altered cell cycle regulation and growth of
      MCF7 cells as well as signaling pathways in MCF7 cells required for malignant
      growth.

PMID- 10930092
TI  - ATM heterozygosity and breast cancer: screening of 37 breast cancer patients for
      ATM mutations using a non-isotopic RNase cleavage-based assay.
AB  - Based upon the results of several epidemiologic studies, it has been suggested
      that women who are carriers for a mutation in the ataxia telangiectasia-mutated
      (ATM) gene are susceptible for the development of breast cancer. Therefore, 37
      consecutive breast cancer patients were screened for the presence of a germline
      ATM mutation using a non-isotopic RNase cleavage-based assay (NIRCA). This paper
      reports the first use of NIRCA for detection of ATM mutations in breast cancer
      patients. Using this assay, no ATM mutations were found in our patient
      population. This result is similar to the findings of other studies that have
      employed approaches complementary to NIRCA.

PMID- 10930093
TI  - Coordinated regulation of two TRAIL-R2/KILLER/DR5 mRNA isoforms by DNA damaging
      agents, serum and 17beta-estradiol in human breast cancer cells.
AB  - A search of the Genebank database revealed that there are two distinct gene
      sequences with the common name of TRAIL-R2/Killer/DR5. Using reverse
      transcription-polymerase chain reaction (RT-PCR), we confirmed the existence of
      two isoforms of TRAIL-R2/Killer/DR5 mRNA, which we have designated the long and
      short isoforms based on their electrophoretic mobility. We found that both the
      long and short mRNA isoforms are ubiquitously expressed in human tissues and cell
      lines. The long form generally predominates, but the proportion of the two
      isoforms varies depending on the tissue type. Treatment of MCF-7 human breast
      cancer cells with the DNA damaging drugs adriamycin, campthothecin, or etoposide
      causes a coordinated up-regulation of both isoforms. Treatment of the p53-mutant
      T-47D breast cancer cell line with adriamycin also results in up-regulation of
      both isoforms, suggesting that adriamycin up-regulates TRAIL-R2/Killer/DR5
      expression independent of functional p53. The expression of both mRNA isoforms
      are increased in MCF-7 cells cultured in charcoal-stripped fetal bovine serum
      compared to normal serum, suggesting that sex steroid hormones may play a role in
      the negative regulation of their expression. This was confirmed in MCF-7 cells
      cultured in stripped serum supplemented with 17beta-estradiol, which also
      resulted in a decrease in the mRNA expression of both isoforms. These results
      demonstrate that the TRAIL-R2/Killer/DR5 gene gives rise to two distinct forms of
      mRNA, and that these two forms are coordinately regulated by DNA damage and
      17beta-estradiol in human breast cancer cells. The functional significance of the
      two isoforms remains to be determined.

PMID- 10930094
TI  - Immunotherapy of a murine T cell lymphoma localized to the brain.
AB  - Mouse YC8 T cell lymphoma was used as a model to determine whether an effective
      immunotherapy procedure could be devised for the treatment of lymphoma localized
      to the brain. Implantation of 5 x 10(4) YC8 cells into the left cerebral
      hemisphere induced rapid loss of the animal's body weight. Severe loss of weight
      and early deaths were observed in the untreated control group. Although
      resistance can be conferred to the brain by immunization of naive BALB/c mice,
      adoptive chemoimmunotherapy procedures were surprisingly not effective in
      inducing remissions in animals with lymphoma confined to the brain. Even passive
      transfer of effector cells from immunized, tumor resistant donor animals combined
      with systemic IL-2 treatment did not impart resistance to recipients with brain
      tumors. However, regression of the intracranial tumor and apparent cures could be
      accomplished, when ex vivo cultured effector cells were transferred
      intravenously.

PMID- 10930095
TI  - Extracellular glutamate and other metabolites in and around RG2 rat glioma: an
      intracerebral microdialysis study.
AB  - The current study determined the extracellular content of glutamate, 10
      additional amino acids, lactate, glucose and some antioxidants in a rodent model
      of malignant glioma, its peritumoral space and the adjacent cortex. RG2 tumors
      were induced in the right frontal cortex of Fischer-344 rats (n = 10) by a
      standardized procedure to obtain a maximum sagittal tumor width of 3-4 mm
      diameter. After confirmation of tumor growth and localization by contrast
      enhanced MRI three microdialysis probes were implanted simultaneously in the
      cortex: at the tumor implantation site (tumor), 2 mm caudally, brain around tumor
      (BAT) and 4 mm caudally (cortex) to the site of implantation. Dialysate
      concentrations of glutamate were increased 3.9-fold in tumor and 2-fold in BAT
      compared with cortex. Glycine was elevated 11.4-fold in tumor and 2.6-fold in
      BAT. Lactate was increased 1.7-fold in tumor, 1.2-fold in BAT. Levels of glucose,
      ascorbic acid and uric acid were not significantly different in tumor, BAT and
      cortex. The increased dialysate levels of glutamate and glycine in the
      peritumoral space may contribute to impaired neuronal function and epileptiform
      activity associated with this tumor type in humans.

PMID- 10930096
TI  - Gene gun transfection of human glioma and melanoma cell lines with genes encoding
      human IL-12 and GM-CSF.
AB  - We used particle-mediated gene transfer by a custom-built gene gun to transfect
      two well-established human glioma (D54MG and U251) and melanoma (SK mel 28 and Ed
      141) cell lines, as well as two glioma lines locally established from primary
      patient tumors (Ed 147 and Ed 149). Using beta-galactosidase as a reporter gene,
      D54MG, U251, Ed 141 and SK mel 28 showed an average transfection efficiency of 15
      40%, whereas Ed 147 and Ed 149 had mean transfection efficiencies of 3% and 5%
      respectively. Twenty-four hours after transfection with the gene encoding human
      interleukin-12 (IL-12), ELISA was performed on cell supernatants (mean of n = 12
      for each cell line). IL-12 expression was extremely variable between the
      different cell lines, ranging from 52 to 1,151 pg/10(6) cells/24 h. Results were
      very similar when cells were exposed to 20,000 rads of gamma irradiation 2 h
      after transfection. When the cell lines were transfected with human granulocyte
      macrophage colony-stimulating factor, 24 h levels were: 13.0 (Ed 147), 17.8 (Ed
      149), 18.6 (Ed 141), 27.4 (D54MG) and 27.7 ng/10(6) cells/24h (U251). SK mel 28
      produced 88.1 ng/10(6) cells/24 h. We conclude that the gene gun can efficiently
      transfect a variety of immortalized, well-established and locally-established
      glioma and melanoma cell lines. High dose gamma irradiation does not adversely
      affect the expression of the foreign gene (IL-12) at 24 h. Significantly,
      transfected cell lines show different levels of expression depending on the
      particular gene/plasmid introduced. Therefore, each cell line has to be assessed
      individually for the level of expression of each introduced gene.

PMID- 10930097
TI  - Cytotoxic effect through fas/APO-1 expression due to vitamin K in human glioma
      cells.
AB  - Congeners of vitamin K have been found to inhibit growth in various rodent and
      human tumor cells, but the mechanisms of the inhibitory action are still not well
      understood. To investigate the modes of actions of vitamin K, we used several
      vitamin K analogs and examined their cytotoxic effect for human glioma cell lines
      RBR17T and U251. The analogs included vitamin K1 (VK1), vitamin K2 (VK2), vitamin
      K3 (VK3), and geranylgeraniol (GGO) which form an unsaturated side chain of VK2.
      Cell viability was estimated by MTT assay. DNA fragmentation was demonstrated by
      gel electrophoresis and flow cytometry. In order to study the mechanism of
      apoptosis, we measured the changes of intracellular reactive oxygen intermediates
      (ROI) and Fas/APO-1 expression by flow cytometry. The results showed: (1) VK2,
      VK3, and GGO inhibited cell growth; (2) VK3 had a more potent cytotoxic effect
      than VK2, and VK3 enhanced the cytotoxic effect of antitumor agents (ACNU and IFN
      beta) in RBR17T cells; (3) VK2, VK3, and GGO induce apoptosis: (4) VK3 increased
      the expression of Fas/APO-1 although VK2 and GGO did not increase its expression
      in glioma cells; (5) VK3 increased the production of intracellular ROI. Catalase
      and reduced glutathione (GSH) inhibited production of intracellular ROI and
      antagonized inhibition of cell-growth induced by VK3, but failed to antagonize
      that of VK2 and GGO. We hypothesize that VK3 induces apoptosis by promoting the
      generation of intracellular ROI and Fas/APO-1 expression. On the other hand, VK2
      and GGO induce apoptosis but most likely by some other unknown pathway.

PMID- 10930099
TI  - Intracranial adenoid cystic carcinoma--a case report.
AB  - Adenoid cystic carcinoma (ACC) is a relatively common malignant neoplasm which
      occurs in the head and neck region, particularly in the salivary glands. It is a
      slow growing, locally aggressive neoplasm with a unique feature of perineural
      spread. Intracranial extension can occur by direct extension, hematogenous
      metastases or by perineural spread. However, the occurrence of primary
      intracranial ACC with no evidence of a primary, is rare, with only ten cases
      reported in reviewed English literature until now. One such case is presented
      here with brief review of literature. This patient showed a good response to
      treatment with surgery followed by post-operative radiotherapy and has remained
      disease free, 32 months after the completion of treatment.

PMID- 10930098
TI  - Growth inhibition of human glioma cells by transfection-induced P21 and its
      effects on telomerase activity.
AB  - The aim of this study is to investigate the effect of the p21 gene transfection
      on the growth of cultured human glioma cell lines, and analyze the telomerase
      activity, and detection of telomerase components in p21 transfectant. The p21
      gene was transfected into human glioma cell lines, U251MG and T98G with our novel
      liposome. The cell growth was assessed by counting the number of trypan blue
      excluding cells in a hemocytometer and flow cytometry analysis. The expression of
      P21 protein and its mRNA were examined by Western and Northern blot analysis. The
      telomerase activity was assayed by TRAP (telomerase repeat amplification
      protocol)/TRAP-HPA (hybridization protection assay) method qualitatively and
      quantitatively. The length of telomere was measured by Southern blot analysis.
      The expression of telomerase components (hTERT, hTERC and TEP1) were examined by
      RT-PCR (reverse transcriptase-polymerase chain reaction). The p21 transfectant
      demonstrated the expression of P21 protein and its mRNA. The p21 transfection of
      human glioma cells results in growth inhibition and G0/G1 arrest. The p21
      transfectant revealed a decrease of telomerase activity and hTERT expression as
      compared with control cells. These results suggest that p21 transfection induces
      G0/G1 arrest in human glioma cells which associates with the reduction in the
      telomerase activity and hTERT expression.

PMID- 10930100
TI  - Intracranial malignant meningioma with abdominal metastases associated with
      hypoglycemic shock: a case report.
AB  - A thirty-year-old male with an intracranial malignant meningioma, first diagnosed
      9 years ago, with three recurrences was admitted with a hypoglycemic shock. The
      blood glucose level was 17 mg/dl, requiring treatment with high doses of
      intravenous and oral dextrose for improvement. A large metastatic tumor in the
      liver was noted. All hormones and peptides influencing blood glucose levels were
      in their normal levels. Chemo-embolization and injection of anti-cancer drugs was
      employed in the management of the metastatic tumor. Positron emission tomography
      was performed to measure the glucose metabolism of the abdominal tumor and it
      indicated that glucose consumption within the tumor was much elevated than the
      surrounding abdominal organs. Hypoglycemia secondary to primary hepatoma or islet
      cell cancer has been frequently described, but a complication of metastatic
      meningioma is an exceedingly rare event. Elevated glucose consumption within the
      tumor might be addressed as one of the reasons for hypoglycemia, not due to the
      elevated serum levels of insulin or IGF, but due to the closely related blood
      glucose level.

PMID- 10930101
TI  - Phase II study of combination taxol and estramustine phosphate in the treatment
      of recurrent glioblastoma multiforme.
AB  - Taxol has activity in the treatment of high grade gliomas but estramustine
      phosphate (EMP) has not been used in this setting. In vitro data demonstrates
      that EMP is cytotoxic to glioma cell lines and estramustine binding proteins are
      expressed by glioma cells. The combination of Taxol and EMP is reported to be
      active in the treatment of hormone-refractory prostate cancer and in taxane
      resistant breast and ovarian cancer. We therefore performed a phase II study to
      assess the activity and toxicity of this combination in high grade gliomas. Taxol
      was given at a dose of 225 mg/m2 intravenously over three hours on day 1 and EMP
      was given at a dose of 900 mg/m2 orally on days 1 through 3. Cycles were repeated
      every three weeks. Twenty patients with recurrent glioblastoma multiforme (GBM)
      were enrolled: 11 male, median age 45 years. All patients received anti-epileptic
      medications and 17 (80%) had received prior chemotherapy. Of 18 evaluable
      patients, two had partial responses (11) and six had stable disease (33%) for a
      minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia
      occurring in only three patients. There were no other grade 3 or 4 toxicities.
      The median time to progression for the cohort was only six weeks (range 3-60+
      weeks). The median overall survival was 12 weeks (range 3-60+ weeks). In
      conclusion, the combination of Taxol and EMP is well tolerated and has modest
      activity in the treatment of recurrent GBM.

PMID- 10930102
TI  - Early MRI findings in high grade glioma.
AB  - Magnetic resonance imaging (MRI) is more sensitive than computerized tomography
      in the detection of many intracerebral lesions; however, the significance of some
      MRI findings may be unclear. Over four years, nine patients, aged 40-79 years,
      have been encountered whose initial MRI scans were negative or had minimal
      abnormalities and soon thereafter had high grade glioma. Initial MRI was
      performed in eight patients for new-onset seizures and one patient for a focal
      deficit. MRI was negative in four of the patients and mildly abnormal in five of
      the patients (small areas of increased T2 and/or minimal enhancement). The
      initial diagnoses usually included inconclusive differentials of stroke and
      infection with neoplasm less frequently considered. Radiographic progression
      leading to the diagnosis of high grade glioma became evident on repeat MRI in 1-8
      months with six patients showing progression within three months. All patients
      underwent surgery and had histologic diagnosis of glioma. Although MRI is quite
      sensitive, four of the initial scans were negative with reasonable quality
      studies. Conversely, in five of the initial scans, the tumors were detected when
      so small that the radiographic findings were not typically diagnostic. Glioma
      must be considered as a possible cause of initial seizures or new neurologic
      deficits in adults with normal or minimally abnormal MRI. In this group, seizures
      were the overwhelming hallmark of presentation. In such a clinical situation,
      close follow-up with short interval repeat MRI should be performed.

PMID- 10930103
TI  - Primary intracerebral rosai-dorfman disease: a case report.
AB  - A 45-year-old woman presented with an isolated, contrast-enhancing brain lesion
      in white matter of the right frontal lobe, preoperatively thought to be either a
      primary brain neoplasm or metastasis. The lesion was demonstrated by histology
      and immunohistochemistry to be Rosai-Dorfman disease. Central nervous system
      (CNS) manifestations of this disease are rare. There have been 27 cases of
      intracranial involvement reported previously. All of them have been dural-based,
      where the disease clinically and radiologically resembles meningioma. To our
      knowledge, this is the first case of an isolated intraparenchymal CNS lesion
      without dural attachment, where the clinical and radiological features resembled
      an intraparenchymal glial neoplasm, lymphoma or metastatic tumor.

PMID- 10930104
TI  - Long-term results of radiation therapy for pituitary adenoma.
AB  - PURPOSE: Local control for pituitary adenomas treated with external beam
      radiation therapy was retrospectively analyzed to evaluate the efficacy of
      radiation. MATERIALS AND METHODS: Thirty-eight patients treated with radiation
      therapy between 1979 and 1994 were analyzed. The median age was 46. Nineteen
      newly diagnosed tumors were treated with surgery and radiation therapy, while the
      others were recurrent cases. Twenty-two tumors were non-functioning, while 10
      produced growth hormone (GH) and three each were prolactin-, and
      adrenocorticotropic hormone (ACTH)-producing tumors. The median-radiation dose
      was 50 Gy in 25 fractions. RESULTS: Non-functioning adenomas and prolactin
      producing adenomas were completely controlled, judging from the absence of tumor
      progression on neuroimaging studies and clinical symptoms, and normalization of
      the serum prolactin level (< 25 ng/ml). On the other hand, local control was
      obtained in only one of the 3 patients with ACTH-producing adenomas, and the
      control rate at 10 years was only 46% for GH-producing adenomas.
      Panhypopituitarism developed in 35% of the patients after radiation therapy. No
      other serious complications were noted. CONCLUSION: Non-functioning pituitary
      adenomas and prolactin-producing adenomas were well controlled with external
      radiation therapy combined with surgery. However, dose escalation might be
      necessary to control GH-or ACTH-producing tumors. It is important to replace
      corticosteroid hormone and thyroid hormone in many patients.

PMID- 10930106
TI  - Is salvage chemotherapy for metastatic breast cancer always effective and well
      tolerated? A phase II randomized trial of vinorelbine versus 5-fluorouracil plus
      leucovorin versus combination of mitoxantrone, 5-fluorouracil plus leucovorin.
AB  - Metastatic breast cancer remains an incurable disease and the median overall
      survival has not significantly improved over the past two decades. Aims of the
      present randomized phase II trial were to analyse activity and toxicity of
      chemotherapies with single agent or with combination regimens in previously
      treated patients with advanced breast cancer. Ninety-nine eligible patients were
      randomized to receive the following chemotherapies: Arm A - vinorelbine 30 mg/m2
      i.v. weekly; Arm B - leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370
      mg/m2 i.v. days 1 --> 5, q 28 days; Arm C - mitoxantrone 12 mg/m2 i.v. only day 1
      + leucovorin 100 mg/m2 i.v. followed by 5-fluorouracil 370 mg/m2 i.v. days 1 -->
      3, q 28 days. Patients characteristics are comparable in the three groups. The
      median number of chemotherapy courses administered was 7, 6 and 5 in arm A, B and
      C, respectively. Objective responses were 24%, 30% and 21% and the median
      duration of responses were 2, 2.5 and 5.5 months in the arm A, B and C,
      respectively. Median overall survivals were 9.5, 9 and 9 months in the three
      arms. No difference was noted comparing the survivals of responding or non
      responding patients. General toxicity was not mild, with 27.5% of patients
      experiencing WHO grade 3-4 toxicities. Our results are similar in the three
      groups of patients and comparable to those reported by other authors.
      Chemotherapy applied to patients with second or subsequent recurrence allow
      objective responses in a small percentage of patients. Moreover responders have a
      negligible prolongation of survival.

PMID- 10930107
TI  - The timing of treatment in breast cancer: gaps and delays in treatment can be
      harmful.
AB  - 'Timing' of treatment in breast cancer may refer to intervals within a single
      management or between different managements. Rates of shrinkage of breast cancers
      in response to treatment are related to histological grade and may be used as
      surrogates for growth rates. Histological grade should predict appropriate timing
      of treatment. Four cases of locally advanced breast cancer that illustrate a
      number of different types of interval are presented. Two tumours of differing
      histological grade (II and III) had been managed by historical 'split-course'
      radiotherapy and two similar grade III tumours were managed by primary medical
      treatment, followed at different intervals by radiotherapy. In the grade III
      tumours different radiotherapy fractionation regimes and effects of varying
      intervals between mangements are compared. The theoretical advantage of shrinkage
      (leading to reoxygenation) during the gap in 'split-course' radiotherapy is
      realized only in relatively slowly growing and shrinking tumours. Grade III
      tumours grow rapidly. They have the potential to shrink rapidly in response to
      appropriate treatment, namely intensive chemotherapy or radiotherapy but not
      hormones. Inadequate treatment leads to growth in intervals between individual
      doses, whether of drugs or radiation, and to failure of local control. The
      advantage of surgery or primary medical treatment will be lost if the interval
      between managements is too long in relation to the volume doubling time.
      Histological grade is a good guide of this parameter; the grade III tumours are
      particularly vulnerable to gaps in treatment.

PMID- 10930105
TI  - Endocrine dysfunctions in patients treated for brain tumors: incidence and
      guidelines for management.
AB  - Endocrine alterations are frequently found in patients undergoing treatment for
      CNS tumors. Careful follow-up aimed at the early detection of recurrences, with
      life-long monitor of hypothalamus-pituitary (HP) function, will also reveal any
      endocrine dysfunctions; indeed, their appropriate diagnosis and treatment may
      determine a significant improvement in the quality of life of these patients.

PMID- 10930108
TI  - Relationship between in vivo drug exposure of the tumor interstitium and
      inhibition of tumor cell growth in vitro: a study in breast cancer patients.
AB  - A novel approach is described to simulate effect site pharmacodynamics of
      anticancer drugs. This approach is based on (i) the in vivo measurement of
      unbound, interstitial drug pharmacokinetics (PK) in solid tumor lesions in
      patients and (ii) a subsequent pharmacodynamic (PD) simulation of the time versus
      drug concentration profile in an in vitro setting. For this purpose, breast
      cancer cells (MCF-7) were exposed in vitro to the time versus interstitial tumor
      concentration profiles of 5-fluorouracil (5-FU) and methotrexate (MTX) from
      primary breast cancer lesions in patients. This led to a maximal reduction in the
      viable cell count of 69% on day 4, and of 71% on day 7 for 5-FU and MTX,
      respectively. This effect was dependent on the initial cell count and was
      characterized by a high interindividual variability. For 5-FU there was a
      significant correlation between the maximum antitumor effect and the intratumoral
      AUC (r = -0.82, p = 0.0005), whereas no correlation could be shown for MTX (r =
      0.05, p = 0.88). We conclude, that the in-vivo-PK / in-vitro-PD model presented
      in this study may provide a rational approach for describing and predicting
      pharmacodynamics of cytotoxic drugs at the target site. Data derived from this
      approach support the concept that tumor penetration of 5-FU may be a response
      limiting event, while the response to MTX may be determined by events beyond
      interstitial fluid kinetics.

PMID- 10930109
TI  - Carcinoma in situ of the breast: correlation of histopathology to
      immunohistochemical markers and DNA ploidy.
AB  - In a consecutive and unselected series of 178 cases of carcinoma in situ of the
      breast (CIS), comprising both ductal (DCIS) and lobular type (LCIS), and a series
      of 48 cases of invasive carcinoma (IC) with predominance of DCIS, the association
      between histopathology, immunohistochemical markers (ER, PgR, MIB-1, c-erbB-2,
      and p53), and DNA ploidy was investigated, in order to discriminate biologically
      different groups. In DCIS, significant correlation was shown between large
      nuclear size and comedonecrosis, both of which showed also strong association to
      DNA aneuploidy, high proliferation activity, low steroid receptor content, and
      overexpression of c-erbB-2 and p53 factors that may indicate an aggressive
      behavior. Small nuclear CIS, whether LCIS or DCIS, on the contrary, were DNA
      diploid with low proliferation, and no cases showed overexpression of c-erbB-2
      and p53. Heterogeneity with respect to the investigated parameters was also a
      frequent finding that may reflect a development complexity. In IC, comparison of
      the DCIS and the invasive component showed similar patterns. No significant
      differences were shown between DCIS without and with invasion. This may indicate
      that none of the investigated parameters on its own are essential for the event
      of invasion.

PMID- 10930110
TI  - Cell-mediated immunity to tumor-associated antigens is a better predictor of
      survival in early stage breast cancer than stage, grade or lymph node status.
AB  - Cell-mediated immune (CMI) responses to tumor-associated antigens (TAA) in the
      early postoperative period were examined for correlations with disease recurrence
      and survival in a 13-year-prospective study of 77 stage 1 and 2 breast cancer
      patients treated with modified radical or radical mastectomy alone. Among the 21
      patients who had positive lymphoproliferative tests using patients' peripheral
      blood mononuclear cells and autologous TAA of breast cancer cells, only one died
      from metastatic disease (5%). Among the 56 patients who had a negative test, 23
      died from metastatic disease (41%). This difference is statistically significant
      (p = 0.002) Three other risk factors including tumor size, nodal status and cell
      differentiation patterns were also analyzed. When these three clinical-pathologic
      criteria were analyzed individually, none reliably predicted disease recurrence
      and survival. Nodal status was the most predictive clinical-pathologic risk
      factor, but was not significant (p = 0.089). The results of this study
      demonstrate the detection of CMI responses against autologous TAA by
      lymphoproliferative assays identifies a sub-set of stage 1 and 2 breast cancer
      patients who are at minimal risk of developing metastatic disease. This testing
      also identifies immunologically unreactive patients who are at risk for disease
      recurrence.

PMID- 10930111
TI  - Pain experienced by women attending breast cancer screening.
AB  - The purpose of this study was to evaluate the pain experience of women during
      mammography for breast cancer screening. Possible associations with personal and
      medical history, sociodemographics and/or situational factors were studied. It
      was also investigated whether this pain influenced the intention to return for
      future breast cancer screening. In the Netherlands, women between 50-75 years are
      invited for screening every two years. A total of 1200 participants were asked to
      fill up a questionnaire. The response rate was 79.5% (n = 954), and 945
      questionnaires contained adequate information for analyses. A total of 689 women
      (72.9%) described mammography as mild to severely painful. In this group,
      compared to the group that reported no pain, the following factors occurred
      significantly more often: sensitive breasts (P = 0.001), family history of breast
      diseases (P = 0.017); expected pain based on former mammography (P = 0.001), high
      education (P = 0.008), anxiety (P = 0.001), breast sensitivity in last three days
      (P = 0.001), insufficient attention of technologist (P = 0.001). Other factors
      like age, hormonal status, breast size and hormone use were not associated with
      the pain experienced. Thirty-two women (3.3%) indicated that they would not
      attend further screening, 25 (2.6%) reported that the pain might deter them, six
      women (0.6%) had other reasons, one woman (0.1%) was sure not to come because of
      severe pain. In conclusion, a large majority of women attending breast cancer
      screening describes mammography as painful (72.9%). Factors associated with pain
      were described. Relatively few women (2.7%) indicated that the pain might deter
      them from future mammography. Recommendations are given to reduce the pain
      experienced during screening mammography.

PMID- 10930112
TI  - Temporal in vitro expansion of the luminal lineage of human mammary epithelial
      cells achieved with the 3T3 feeder layer technique.
AB  - Human mammary epithelial cells from reduction mammoplasties were serially
      propagated in vitro from single cells and/or cell clusters using the NIH 3T3 cell
      feeder layer technique. In seven passages 46 cell population doublings, corrected
      for plating efficiency were achieved. The plating efficiency of epithelial cells
      in the primary culture was 0.2%. During subsequent passages it rose to 10-12% and
      decreased sharply towards the end of the culture life. In the third and fourth
      passages temporal prevalence of luminal cells was observed. The critical
      conditions for prevalence of the luminal phenotype were found to be the initial
      dissociation and optimum seeding density during subculturing. In primary
      cultures, after optimum dissociation of 0.15 cm3 mammary tissue with 0.05%
      collagenase A (Boehringher-Mannheim) in Eagle's MEM for 16 h at 37 degrees C, the
      yield on day 13 was 20 large colonies of 8-10 mm diameter. About 30% of the
      epithelial cells, which stained positively for the luminal cell marker
      cytokeratin 19, occupied colony centres. The remaining 70% were actin positive
      myoepithelial cells at the periphery. In subsequent passages, when using the
      optimum seeding density of 2 x 10(5) cells per 60 mm culture dish, the proportion
      of luminal cells gradually increased to 90% on day 35 in the fourth passage. A
      sudden rise in the proportion of rapidly growing myoepithelial cells to 65% was
      observed in the fifth passage. In the sixth and seventh passage small colonies
      were formed, most of which contained at least one keratin-19-positive (luminal)
      cell. Cells of human breast carcinomas are considered to be of luminal origin.
      Therefore, the described approach can be useful in studies of cell and molecular
      biology of mammary carcinomas.

PMID- 10930113
TI  - Autocrine and paracrine growth inhibitors of breast cancer cells.
AB  - Breast epithelial cells produce both mitogens and growth inhibitors which are
      involved in the control of mammary gland development through autocrine and
      paracrine pathways. While the mechanisms of action of several growth factors have
      been well established and related strategies proposed for breast cancer therapy,
      little is known concerning growth inhibitors. In this review, we present an
      overview of current information about major autocrine and paracrine growth
      inhibitors of breast epithelial cells, and we discuss their potential functions
      in the control of breast cancer development.

PMID- 10930114
TI  - Aberrant expression of TSG101 in Taiwan Chinese breast cancer.
AB  - Functional inactivation of the tsg101 gene in mouse fibroblasts results in cell
      transformation and the ability to form metastatic tumors in nude mice. The human
      tsg101 gene was mapped to chromosome 11q15.1-2 and found to mutate in some cancer
      patients. To test the expression pattern of the tsg 101 gene in Chinese breast
      cancer patients, we analyzed the mRNA by RT-PCR in 51 breast cancer patients. The
      full-length tsg101 and 7 truncated transcripts were detected in both normal and
      matched tumor tissues. A short transcript with a deletion of nucleotides 154-1054
      is frequently presented in late-stage breast cancers. TSG101 protein expression
      was also detected by Western blot analysis in 30 breast cancer patients. A
      predicted full-length 46 kDa and three proteins with smaller molecular weight
      were detected. The full-length 46 kDa protein was less expressed in tumor
      specimens. Immunohistochemical stains from 10 patients of each stage 0-4 revealed
      that TSG101 protein was predominantly present in the cytoplasm. Cell nuclei were
      occasionally immunopositive and the chromosomes were deeply stained during cell
      division. The intracellular location and the expression of TSG101 protein were
      both not stage-dependent in primary breast cancers. In addition, normal mammary
      glands were more homogenously immunopositive than invasive ductal carcinoma.
      These results support the notion that the aberrant expression of TSG101 in breast
      cancer is associated with altered cell growth.

PMID- 10930115
TI  - Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin
      expanders after mastectomy for breast cancer.
AB  - BACKGROUND: Immediate breast reconstruction (IBR) by means of skin expander is
      currently one of the most widely used methods of breast reconstruction in
      mastectomized patients. However, given that many breast cancer patients usually
      receive adjuvant chemotherapy, the adoption of IBR raises new questions
      concerning possible cumulative toxicity. The present study reports our experience
      in the use of concurrent adjuvant chemotherapy and immediate breast
      reconstruction with skin expander after mastectomy for breast cancer and the
      acute cumulative toxicity of the treatments. METHODS: We evaluated a consecutive
      series of 52 breast cancer patients who have received IBR by skin expander after
      radical mastectomy and adjuvant chemotherapy concurrently during skin expansion
      between 1995 and 1998 (IBR/CT group). We identified two series of control
      patients treated during the same period: 51 consecutive patients undergoing
      radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63
      consecutive patients undergoing radical mastectomy and adjuvant chemotherapy
      without IBR (CT group). For each patient, we evaluated the incidence of surgical
      complications and chemotherapy's side effects and dose intensity. RESULTS: The
      interval between surgery and the start of expander inflation was similar in
      IBR/CT (range 0-19, median 5 days) and IBR groups (range 0-40, median 5 days) and
      the timing of inflation was not influenced by chemotherapy. The overall incidence
      of surgical complications in patients undergoing IBR was low: seroma in eight
      cases, infection in one, skin necrosis in one, expander rupture in two and
      erythema in three. There were no statistically significant differences in the
      distribution of complications between the IBR/CT and IBR groups. The dose
      intensity of chemotherapy was similar between IBR/CT and CT groups, with a median
      dose intensity of 96% and 95% of the projected dose, respectively. The only
      statistically significant difference in terms of chemotherapy side effects (p =
      0.03) was that stomatitis was more frequent and intense in the CT than in the
      IBR/CT group. CONCLUSIONS: Concurrent treatment with IBR and adjuvant
      chemotherapy appears feasible and safe, it does not increase acute surgical
      complications or chemotherapy side effects, and does not require any changes in
      dose intensity or the timing of inflation.

PMID- 10930116
TI  - Evaluation of stereotactic core needle biopsy (SCNB) of the breast at a single
      institution.
AB  - Stereotactic core needle biopsy (SCNB) has become a popular method for diagnosis
      of occult breast abnormalities. There are few large series of SCNB from a single
      institution. Data on patients undergoing SCNB for mammographic abnormalities were
      collected prospectively over 43 months at a university hospital. Mammographic
      findings were categorized as benign, probably benign, indeterminate, suspicious
      or malignant. For lesions with SCNB pathology that were non-diagnostic, showed
      atypical hyperplasia or malignancy (in situ or invasive), or were discordant with
      the pre-biopsy mammogram findings, surgical excision was recommended. Subsequent
      surgical pathology was reviewed. All remaining lesions were followed
      mammographically after SCNB. SCNB was performed on 692 lesions in 607 patients.
      There were 79 malignancies, for a positive SCNB rate of 11.4%. The 349 SCNB
      performed for benign, probably benign and indeterminate lesions on mammography
      had a positive SCNB rate of only 4%. Surgery was recommended for 127 (18.3%)
      lesions, while 565 (81.6%) were followed mammographically after SCNB. A
      compliance rate of 61 % for at least one follow-up mammogram was obtained, with a
      median follow-up of 17.2 months and with no cancers found. The sensitivity for
      malignancy with SCNB was 93%. SCNB provides a minimally invasive method to assess
      mammographic abnormalities. Abnormalities considered radiographically to be other
      than malignant or suspicious yielded few cancers. In this series a low positive
      SCNB rate resulted in no false negatives on mammographic follow-up. The optimal
      positive biopsy rate for SCNB is debatable.

PMID- 10930117
TI  - Expression of LFA-1 (CD11a/CD18) and ICAM-1 (CD54) in an animal model of renal
      interstitial fibrosis induced by unilateral ureteral obstruction.
AB  - Unilateral ureteral obstruction (UUO) has been used as an experimental model to
      induce tubulointerstitial damage and interstitial fibrosis. UUO is characterized
      by cellular proliferation, accumulation of inflammatory cells, and subsequent
      replacement of renal parenchyma by fibrous tissue. The influx of inflammatory
      cells into the renal interstitium is mediated by adhesion molecules. In this
      study, the development of fibrosis in the UUO model of the rat was examined and
      its relation to the time course of LFA-1 and ICAM-1 expression was assessed by
      immunohistochemistry. An increase in interstitial connective tissue was detected
      on day 10 after UUO, with a maximum on day 35. After unilateral ureteral
      obstruction, LFA-1 was prominently expressed in interstitial infiltrates, and to
      a lesser degree in glomerular areas. An initial increase in LFA-1-positive cells
      was noted already on day 10, with a maximum on day 20 and a decline on day 25.
      During the time course of 35 days after UUO, we observed an increase in ICAM-1
      expression in the vascular endothelium, in tubular epithelium and in interstitial
      areas. This study shows that LFA-1 expression and ICAM-1 expression are
      concordant and that this process is associated with increasing interstitial
      fibrosis. ICAM-1 interstitial tissue may facilitate the homing and persistence of
      an interstitial infiltrate by ICAM-1/LFA-1 interactions, thereby preceding the
      development of renal interstitial fibrosis.

PMID- 10930118
TI  - Myofibroblast accumulation in healing rat myocardium due to long-term low-dosage
      nitric oxide synthesis inhibition.
AB  - Inhibition of nitric oxide synthesis causes hypertension, myocardial damage and
      repair in rats. The myocardial healing process includes changes in extracellular
      matrix composition associated with the phenotypic modulation of fibroblasts.
      Early and later lesion areas showed a population of spindle-shaped cells
      expressing alpha-smooth muscle actin content. These cells apparently are
      associated with type III collagen and fibronectin accumulation in the ischemic
      lesion areas contributing to maintaining of the mechanical performance of the
      heart through out the healing process.

PMID- 10930119
TI  - Transforming growth factor-alpha, epidermal growth factor receptor, and PCNA
      immunoexpression in uterine leiomyosarcomas and leiomyomas in B6C3F1 mice.
AB  - The role of growth factors in the development of murine uterine mesenchymal
      tumors is unknown. In this study, immunohistochemical expression of transforming
      growth factor alpha (TGF-alpha) and its receptor epidermal growth factor (EGF-R)
      was assessed in spontaneous uterine leiomyomas and leiomyosarcomas in B6C3F1
      mice. Cell proliferation, which has been induced by some growth factors, was
      evaluated by immunohistochemical detection of an endogenous marker of cell
      proliferation, proliferating cell nuclear antigen (PCNA). PCNA labeling indices
      were determined and compared to the intensity and distribution of TGF-alpha
      staining in sequential sections of control myometrium or tumor tissue. Results
      showed uterine leiomyosarcomas had positive cytoplasmic staining for TGF-alpha;
      however, all uterine leiomyomas evaluated were negative. Positive EGF-R staining
      was also observed in the uterine leiomyosarcomas, but not in the leiomyomas. EGF
      R immunoexpression was detected primarily within the cytoplasm of the
      leiomyosarcoma cells, with occasional nuclear immunoreactivity.
      Immunohistochemical staining for PCNA was more intense and there were increased
      numbers of positively staining nuclei in the leiomyosarcomas compared to samples
      of control myometrium or leiomyomas. The mean labeling index for the uterine
      leiomyosarcomas (7.40%) was significantly (p < 0.01) higher than that of
      leiomyomas (0.29%) and control uterine myometrium (0.13%). We conclude, that TGF
      alpha and its receptor, EGF-R, are expressed more intensely in uterine
      leiomyosarcomas, compared to leiomyomas in B6C3F1 mice. Immunoexpression of TGF
      alpha may be an important biomarker of malignancy in uterine smooth muscle tumors
      in mice. Futhermore, TGF-alpha may play a critical role in increased
      proliferation of uterine smooth muscle tumor cells as suggested by increased
      immunolocalization of PCNA in rodent leiomyosarcomas expressing TGF-alpha,
      although other factors regulating cell replication can not be ruled out.

PMID- 10930120
TI  - Clinical, microbiological and pathological observations in laboratory beagle dogs
      infected with leptospires of the serogroup Sejroe.
AB  - In beagle dogs infections with two different serovars of serogroup Sejroe are
      described. Saxkoebing titres of 27 beagle dogs were controlled for 7 to 9 months.
      Dogs serologically positive for saxkoebing showed no clinical symptoms. From the
      urine, an isolation of the microorganisms was possible. At necropsy, there was no
      evidence of any changes related to the proven infection. Histopathologically, in
      animals with persistent titres a mild interstitial nephritis was found. No
      changes were observed in the liver. Another three beagle dogs died after about
      two days of acute clinical illness with febrile temperature, exsiccosis and
      hematuria. Histopathologically, incipient inflammation was seen in the liver and
      kidneys. Besides, hepatic cholestasis, renal hemoglobin casts and degeneration of
      renal tubular epithelia were observed. In concurrent animals, an infection with
      another serovar of serogroup Sejroe was proven serologically. This serovar was
      also isolated. Transmission and spreading of leptospirosis within animals
      shelters or laboratories from clinically healthy carriers and its prevention as
      well as the protection of animal caretakers are discussed. Since leptospires are
      sensitive to physical and chemical methods of disinfection, this is easily
      feasible. However, the optimal prevention appears to be a stock- or population
      specific vaccination.

PMID- 10930121
TI  - Brown bullhead (Ameiurus nebulosus) skin carcinogenesis.
AB  - Alternative models using fish species have been tested in liver toxicity and
      carcinogenesis bioassays. Similar models have not been developed for skin. The
      brown bullhead (Ameiurus nebulosus) has shown potential as a model for skin
      carcinogenesis studies due to its sensitivity to environmental chemical
      pollutants. The present study is an initial morphologic and biochemical
      characterization of the normal and neoplastic brown bullhead skin to assess its
      suitability as a model of skin carcinogenesis. Brown bullhead were removed from
      Back River in the Chesapeake Bay region, an area historically polluted with heavy
      metals and polycyclic aromatic hydrocarbons. Histology, histochemistry, and
      electron microscopy were used to stage the morphologic development and
      progression of neoplasia in skin. The distribution of keratin, a family of
      structural proteins with altered expression in mammalian tumorigenesis, was
      analyzed with one and two dimensional gel electrophoresis and nitrocellulose
      blots of extracts from normal skin. Keratin expression in skin and other organs
      was also assessed with immunohistochemistry using AE1, AE3, and PCK 26
      antibodies, and the proliferation index in skin and neoplasms with PCNA antibody.
      Skin lesions appeared to progress from hyperplasia through carcinoma, and the
      proliferation index was increased in papilloma. Also in papilloma, intercellular
      interdigitations appeared increased and desmosomes decreased which may in future
      studies correlate with changes in expression of other molecular markers of
      neoplastic progression. Both Type I and Type II keratin subfamilies were detected
      in skin using gel electrophoresis with the complimentary keratin blot-binding
      assay. For further development of the brown bullhead model, future studies can
      compare and relate these baseline data to alterations in expression of keratin
      and other markers in fish neoplasms and to molecular events which occur in man.

PMID- 10930122
TI  - Incidence and spectrum of spontaneous neoplasms in male and female CBA/J mice.
AB  - Although CBA mice are occasionally used in biomedical research, little is known
      about their life-data and diseases ("background pathology"). Therefore, it was
      the aim of this study to determine the life expectancy, spectrum and incidence of
      spontaneous neoplasms of the inbred CBA/J mouse strain. A total of 631 untreated
      mice (293 females; 338 males) were kept from birth to death under standard
      laboratory conditions. A complete histological examination was performed on all
      organs/tissues. In female CBA mice, the average lifespan was 94 weeks, while the
      mean age in males was 85 weeks. Neoplastic lesions were observed in 70% (238/338)
      of the males and 51% (150/293) of the female CBA/J mice. Tumours of the liver,
      lung and haematopoietic tissue were common in males, while tumours of the lung,
      ovary and haematopoietic tissue were the most frequent neoplasms in female CBA/J
      mice.

PMID- 10930124
TI  - Picryl chloride-induced allergic dermatitis in IQI/Jic female mice.
AB  - IQI/Jic (IQI) mice are an ICR-derived inbred strain developed in Japan, and it is
      known that aged females of this strain develop allergic dermatitis of spontaneous
      nature. In the present study, young IQI female mice which were sensitized with
      picryl chloride (PCL) to the shaved skin of abdomen and then topically applied
      with PCL to the ear at 4, 11, 18 and 25 days after the sensitization were
      examined. The ear swelling response increased rapidly after the 1st application,
      peaked after the 2nd one, and then gradually decreased. Histopathologically,
      edema with inflammatory cell infiltration developed after the 1st application and
      progressed after the 2nd one. The number of mast cells, CD4-positive cells and
      MHC class II-positive cells became prominent accompanied with epidermal
      thickening and dermal fibroplasia after the 4th application when clear elevation
      of total serum IgE levels was observed in many mice. Compared with the dermatitis
      induced in the same way in BALB/c female mice, the nature was similar with each
      other but the degree was obviously severer in IQI female mice. IQI female mice
      are considered to be a useful laboratory animal for the investigation of allergic
      dermatitis.

PMID- 10930123
TI  - The mechanism of nitric oxide and/or superoxide cytotoxicity in endothelial
      cells.
AB  - We examined the mechanism of nitric oxide (NO) and/or superoxide (O2-)-induced
      cytotoxicity and the importance of thiols in endothelial cells by treating the
      cells with superoxide dismutase (SOD), catalase (CAT) and hemoglobin (Hb).
      Pyrogallol, a O2 generator and precursor of hydrogen peroxide (H2O2), had potent
      cytotoxic effects on the endothelial cells, but this effect was completely
      abolished by SOD/CAT. Hb, a NO scavenger, protected the endothelial cells from
      sodium nitroprusside-induced cytotoxicity. The cytotoxic effect of 3
      morpholinosydnonimine (SIN-1), which is thought to form peroxynitrite (ONOO-) as
      a simultaneous O2- and NO generator, was completely blocked by SOD/CAT or Hb. On
      the other hand, pretreatment of endothelial cells with diethylmaleate, a
      glutathione depleter, aggravated the cytotoxicity induced by SIN-1, which was
      prevented by addition of exogenous glutathione and/or SOD/CAT. These data suggest
      that the cytotoxicity induced by NO, O2- and ONOO- can be blocked by glutathione,
      and that this is an important cellular protective mechanism against these
      reactive oxygen species.

PMID- 10930125
TI  - 1,2-Dimethylhydrazine carcinogenesis in CBA male mice prenatally treated with
      diethylstilbestrol.
AB  - CBA female mice, at the 17th day of pregnancy, received single intraperitoneal
      injection of diethylstilbestrol (DES) at the dose of 1 mg/kg body weight (b. w.).
      Their descentands at the age of 2 months started receiving subcutaneous
      injections of 1,2-dimethylhydrazine (DMH) at the dose level of 8 mg(base)/kg b.
      w., total 15 weekly injections. Prenatal DES treatment of male mice considerably
      accelerated the development and increased the incidence of DMH-induced androgen
      dependent renal adenomas and, notably, renal capsule angiosarcomas (RCA). In
      males receiving prenatal DES (without subsequent DMH-treatment), there was a
      statistically significant increase of renal adenomas and 9% of RCA were observed
      which are exceedinly rare in untreated mice. The enhancement of androgen
      dependent tumourigenesis may be considered as an indication, even though
      indirect, of the hyperandrogenization produced in male mice by the prenatal DES
      treatment.

PMID- 10930126
TI  - Characteristics of polyarthritis in rabbits by hyperimmunization with attenuated
      Enterococcus faecalis.
AB  - To produce polyarthritis and rheumatoid factor like substance (RFLS), rabbits
      were hyperimmunized intravenously with 0.02% thimelosal (TMS)-treated
      Enterococcus faecalis (E. faecalis) as a persistent bacterial flora. Swelling of
      knee joints occurred at a rate of 41% (27/66), and of shoulder joints at a rate
      of 25% (17/66) while that of elbow joints occurred at a rate of 4.5% (3/66). On
      culturing of knee joint fluids, no colonies appeared while 2/4 fluid specimens
      from the shoulder joints gave positive colonies for 78 days after the first
      immunization; thereafter, no colonies appeared. On histological examination, in
      early stages, acute inflammatory reactions with degenerative changes of synovial
      tissue was observed. In later stages, chronic inflammatory changes, proliferation
      of synovial cells with pannus formation, destruction of articular cartilage and
      subchondral bone were observed. RFLS titer showed bi-phasic peaks at 11 days and
      41 days after the first immunization. A high incidence of polyarthritis,
      particularly knee joints, occurred. Thus, hyperimmunization with attenuated E.
      faecalis as a normal intestinal flora may provide an animal model of chronic
      polyarthritis.

PMID- 10930127
TI  - Acute lead intoxication in vivo affects myelin membrane morphology and CNPase
      activity.
AB  - The aim of the present study was to assess the sensitivity of central nervous
      system myelin to acute Pb-toxicity in an animal model, that imitates lead
      toxicity in occupationally exposed workers, or in occasional incidents of
      poisoning. Our results indicated that in vivo acute lead intoxication affected
      both the morphology of myelin and enzymatic activity of the myelin marker, CNPase
      (2'3'-cyclic nucleotide 3'-phosphodiesterase). The multilayered structure of
      myelin sheaths was regionally disturbed, with loosely arranged membranes or ovoid
      shaped swollen fragments. The activity of CNPase was diminished and Michaelis
      Menten kinetics showed a decreased affinity and lower velocity of the enzyme.
      These data suggest that the disturbances in CNPase activity may contribute, in
      some extent, to the changes in myelin morphology observed in acute Pb
      intoxication.

PMID- 10930128
TI  - CULTEX--an alternative technique for cultivation and exposure of cells of the
      respiratory tract to airborne pollutants at the air/liquid interface.
AB  - The assessment of cytotoxicity of air contaminants such as gaseous or particulate
      compounds and complex mixtures has traditionally involved animal experiments, due
      to the difficulties in exposing cell cultures directly to these substances. New
      cultivation and exposure techniques enhance the efficiency of in vitro studies,
      as demonstrated by a new experimental system called CULTEX which allows direct
      exposure of cells at the air/liquid interface. In this case, human bronchial
      epithelial cells are cultivated on porous transwell membranes in a device
      allowing intermittent medium supply. The medium is pumped into a special modular
      culture unit through the transwell membrane supporting the cells. At certain time
      intervals, the medium is completely removed and the cells can be maintained and
      exposed at the air/liquid interface until the next medium supply without loss of
      viability. In comparison to conventional submersed culture conditions, the cells
      have been grown on transwell membranes using the new pulse submersion technique.
      There are no deleterious effects on cell viability due to the direct exposure to
      airborne pollutants. Thus, the introduction of these new cultivation and exposure
      techniques offers new testing strategies for the toxicological evaluation of
      inhalable soluble and inert substances as well as complex mixtures.

PMID- 10930129
TI  - Reduced muscle vascular resistance in intrauterine growth restricted newborn
      piglets.
AB  - It has been shown that asymmetrical intrauterine growth restriction is denoted by
      disproportional reduction of muscle mass compared to body weight reduction.
      However, the effects of IUGR on regional vascular resistance and blood flow of
      skeletal muscles and their contractile function have not been studied until now.
      Therefore, muscle blood flow (MBF) and isometric force output of serial
      stimulated hindlimb plantar flexors was measured in thiopental -anesthetized
      normal weight (NW; n = 9) and intrauterine growth restricted (IUGR; n = 9) one
      day-old piglets. Additionally, muscle vascular resistance (MVR) and thyroid
      hormones were estimated. MBF was found to be markedly increased in IUGR piglets
      by 36% with a concomitant MVR reduction of 37% (p < 0.05). Isometric force of the
      plantar flexors was considerably higher in NW than in IUGR piglets (p < 0.05).
      However, amount of muscle fatigue was more pronounced in NW piglets (9.1+/-2.8%)
      than was in IUGR piglets (3.7+/-2.3%) (p < 0.05). Furthermore, specific tension
      of NW muscles (18.8+/-0.7 N/cm2) was significantly lower than for IUGR muscles
      (21.2+/-0.9 N/cm2) (P<0.05). IUGR newborn piglets exhibited increased plasma
      levels of thyroxine (T4) (p < 0.05), whereas triiodothyronine (T3) showed similar
      values in both animal groups. These data clearly indicate that muscle
      hemodynamics and contractile function are more developed in newborn IUGR piglets.
      Furthermore it is suggested that the improved tolerance to fatigue during
      isometric contractions may indicate an increased oxidative capacity of calf
      muscles due to intrauterine growth restriction.

PMID- 10930130
TI  - Prevention of death of axotomized hypoglossal neurones and promotion of
      regeneration by chitin grafting.
AB  - 1. Chitin is known to promote skin wound healing. In this study, chitin, prepared
      from Zuwai crab shell, was used as a bridge between the proximal and distal
      stumps of cut hypoglossal nerves in shrews. We compared the effects of chitin on
      the regeneration of transected right hypoglossal nerve axons, with those of
      porcine dermis, bovine dermal aterocollagen, and autologous nerve bundles. 2. To
      assess the survival of neurones, the size of neuronal cell body, and number of
      motoneurones were determined in the absence of any bridged material and in the
      presence of porcine dermis, bovine dermal aterocollagen, chitin, or autologous
      nerve bundles as a bridge. 3. Our results revealed a significantly better outcome
      in chitin and autologous nerve bridged groups; the size of neuronal cell body and
      number of hypoglossal neurones were higher than in the other groups. Chitin also
      enhanced the regeneration of neurones; the number of horseradish peroxide
      positive neurones indicative of repaired axonal processes was significantly
      higher in chitin and autologous nerve-bridged groups than in other groups. 4. Our
      results demonstrated that the use of chitin sheet or autograft successfully
      prevented the death of severed neurones and promoted the regeneration of the
      lesioned nerve. Although the mechanisms underlying the effects of chitin are
      still unknown, chitin seems to be a potentially useful biocompatible material for
      nerve repair and regeneration.

PMID- 10930131
TI  - Involvement of glial endothelin/nitric oxide in delayed neuronal death of rat
      hippocampus after transient forebrain ischemia.
AB  - 1. We examined time- and cell-type-dependent changes in endothelin (ET)-1-like
      immunoreactivity, ET receptors binding and nitric oxide (NO) synthase (NOS)
      activity in CA1 subfields of the hippocampus of stroke-prone spontaneously
      hypertensive rats subjected to a 10-min bilateral carotid occlusion and
      reperfusion. 2. Microglia aggregated in accord with neuronal death and expressed
      a high density of ET(B) receptors and an intense NOS activity in the damaged CA1
      pyramidal cell layer, 7 days after the induced transient forebrain ischemia. The
      increased NOS activity and ET(B) receptor in microglia disappeared 28 days after
      this transient ischemia. 3. In contrast to microglia, astrocytes presented a
      moderate level of ET-1-like immunoreactivity, ET(B) receptors, and NOS activity
      in all areas of the damaged CA1 subfields, 7 days after the ischemia. These
      events were further enhanced 28 days after the ischemia. 4. In light of these
      findings, the possibility that the microglial and the astrocytic ET(B)/NO system
      largely contributes to development of the neuronal death and to reconstitution of
      the damaged neuronal tissue, respectively, in the hippocampus subjected to a
      transient forebrain ischemia would have to be considered.

PMID- 10930132
TI  - Identification of a novel gene encoding a PrP-like protein expressed as chimeric
      transcripts fused to PrP exon 1/2 in ataxic mouse line with a disrupted PrP gene.
AB  - 1. Mouse lines lacking prion protein (PrP(C)) have a puzzling phenotypic
      discrepancy. Some, but not all, developed late-onset ataxia due to Purkinje cell
      degeneration. 2. Here, we identified aberrant mRNA species in the brain of Ngsk
      Prnp0/0 ataxic, but not in nonataxic Zrch Prnp0/0 mouse line. These mRNAs were
      chimeric between the noncoding exons 1 and 2 of the PrP gene (Prnp) and the novel
      sequence encoding PrP-like protein (PrPLP), a putative membrane glycoprotein with
      23% identity to PrP(C) in the primary amino acid structure. The chimeric mRNAs
      were generated from the disrupted Prnp locus of Ngsk Prnp0/0 mice lacking a part
      of the Prnp intron 2 and its splice acceptor signal. 3. In the brain of wild-type
      and Zrch Prnp0/0 mice, PrPLP mRNA was barely detectable. In contrast, in the
      brain of Ngsk Prnp0/0 mice, PrP/PrPLP chimeric mRNAs were expressed in neurons,
      at a particularly high level in hippocampus pyramidal cells and Purkinje cells
      under the control of the Prnp promoter. 4. In addition to the functional loss of
      PrP(C), ectopic PrPLP expression from the chimeric mRNAs could also be involved
      in the Purkinje cell degeneration in Ngsk Prnp0/0 mice.

PMID- 10930133
TI  - Forskolin modulates acetylcholine receptor gating by interacting with the small
      extracellular loop between the M2 and M3 transmembrane domains.
AB  - 1. Forskolin acts as an allosteric modulator of muscle-type nicotinic
      acetylcholine receptors. Receptors from mouse muscle and Torpedo electroplax
      demonstrate differential sensitivity to inhibition by forskolin. Previous work
      from this laboratory suggested that the gamma subunit is responsible for this
      differential sensitivity. 2. We have used a series of mouse/Torpedo species
      chimeric gamma subunits to further define the site of forskolin interaction with
      the gamma subunit. Analysis of the patterns of forskolin inhibition of receptors
      containing mouse/Torpedo chimeric gamma subunits along with the mouse alpha,
      beta, and delta subunits suggests that forskolin interacts with the small
      extracellular domain that links the M2 and M3 transmembrane domains (the M2-M3
      linker). 3. We suggest that the M2-M3 linker domain plays an important role in
      the transduction of ligand binding to the conformational changes that result in
      channel opening.

PMID- 10930136
TI  - What is the true resting potential of small cells?

PMID- 10930135
TI  - Effect of inorganic and organic tin compounds on ACh- and voltage-activated Na
      currents.
AB  - 1. Inorganic tin and organotin compounds, occurring in aquatic ecosystems, are
      toxic and can cause behavioral abnormalities in living organisms. To determine
      the possible neuronal basis of these actions, the effects of both forms of Sn
      were studied on identified neurones of the mollusk, Lymnaea stagnalis L. 2. SnCl2
      caused a dose-dependent decrease in the acetylcholine (Ach)-induced inward
      current. The effective threshold concentration, measured by a two microelectrode
      voltage clamp technique, was 0.1 microM, and the maximal effect occurred at 5
      microM SnCl2. The depression of the inward current was greater after a 10 min
      preapplication (20%) than after 3 min treatment (7%). 3. The next series of
      experiments compared the actions of inorganic or organic tin compounds. In whole
      cell clamp experiments both (CH3)2SnCl2 and (CH3)3SnCl, like inorganic Sn,
      decreased the amplitude of Ach-induced current. Increasing the duration of the
      preapplication time resulted in an increase in the effect, but the action was not
      reversible. SnCl2 treatment caused a concentration-dependent alteration (initial
      potentiation followed by depression) of the amplitude of I(Na(V)) over the whole
      voltage range and slightly shifted the I-V curves to the left. In contrast,
      trimethyl tin decreased the amplitude of I(Na(V)) only at high concentration (100
      microM). The activation time course of I(Na) was increased (tau = 0.43 ms in
      control and 0.55 ms in Sn), but Sn did not alter the inactivation parameters (tau
      = 3.43 and 3.41 ms). 4. These results support earlier findings that agonist- and
      voltage-activated channels are direct targets of toxic metals. We conclude that
      tin in both inorganic and organic forms acts at neuronal membranes to modulate
      synaptic transmission through direct actions on agonist-activated ion channels,
      and suggest that these actions may be the basis of the altered behavior of
      animals in tin-polluted environments.

PMID- 10930134
TI  - Gangliosides affect membrane-channel activities dependent on ambient temperature.
AB  - 1. The functional properties of biological membranes depend on their molecular
      composition. In regard to this, charged glycosphingolipids play an outstanding
      role in the functional adaptation of membranes to different temperatures. 2. In
      order to shed some light on the respective functional properties of complex
      membraneous glycosphingolipids, the effects of altered temperatures (5-40 degrees
      C) on planar lipid bilayers made from diphytanoylphosphatidylcholine (DPPC) and
      alamethicin as an ion channel was analyzed in the presence of either a
      sialoglycosphingolipid (less polar disialoganglioside GD1a or highly polar
      tetrasialoganglioside GQ1b) or phosphatidylserine (PS; as control). 3. Different
      to the control bilayers made from DPPC or DPPC + PS, the bilayers containing
      gangliosides had specific maxima in alamethicin conductance and stabile life
      times. Changes in pore-state conductances indicate structural effects based on an
      interaction of the large (negatively charged) ganglioside headgroups with the
      alamethicin pores. 4. The results concerning open time and closed time of
      channels seem to be based on the gangliosides changing the viscosity of the
      bilayer and possibly introducing phase transitions. 5. Thus, the findings suggest
      that gangliosides (1) directly affect channel molecules via their headgroups and
      (2) may additionally affect the fluidity of membranes in order to maintain
      membrane homeoviscosity in areas surrounding ion channels independent from the
      environmental temperature. 6. The effects of gangliosides may be of special
      interest in describing the ability of neuronal adaptation of vertebrates to
      temperature and more general regarding the functional adaptation of neurons.

PMID- 10930137
TI  - Na,K-ATPase in the myocardium: molecular principles, functional and clinical
      aspects.
AB  - The role that Na,K-ATPase plays in Na+ and K+ antiport through the sarcolemma, in
      cation-homeostasis in cardiomyocytes as well as in excitation-contraction
      coupling and cell signalling in the myocardium is now widely recognized. It was
      its key importance for the cell membrane function that kept this enzyme
      intensively studied during the last three decades and finally brought to its
      discoverer the deserved Nobel Prize. Almost weekly are appearing new data
      concerning structure, function, regulation and role of the Na,K-ATPase in
      different physiological and pathological conditions. The special importance of
      the enzyme for heart function as well as the great amount of data that is
      concerned specifically with the heart Na,K-ATPase and accumulated since yet,
      started to call for setting them in order. The present paper updates basically
      important data on the cardiac Na,K-ATPase in relation to its specific properties,
      molecular mechanisms of function, mode of action, humoral and pharmacological
      modulation, adaptability, physiological role and clinical aspects.

PMID- 10930138
TI  - Bovine monocyte-derived macrophage function in induced copper deficiency.
AB  - The effect of molybdenum-induced copper deficiency on monocyte-derived macrophage
      function was examined. Five female calves were given molybdenum (30 ppm) and
      sulphate (225 ppm) to induce experimental secondary copper deficiency. Oxidant
      production by bovine macrophages was measured after stimulation with phorbol
      myristate acetate (PMA) and opsonized zymosan (OpZ). Lipoperoxidative effects
      inside of macrophage, superoxide dismutase activity, superoxide anion and
      hydrogen peroxide formation were determined. Copper deficiency was confirmed from
      decreased serum copper levels, and animals with values less than 5.9 micromol/l
      were considered deficient. The content of intracellular copper decreased about
      40% in deficient cells compared with the controls. The respiratory burst activity
      determined by nitroblue tetrazolium reduction was significantly impaired with
      both stimulants used. Superoxide anion formation was less affected than hydrogen
      peroxide generation. In addition, increased lipid peroxidation was observed. It
      could be concluded that the effect of these changes may impair the monocyte
      derived macrophage function in the immune system.

PMID- 10930139
TI  - Estradiol affect Na-dependent Ca2+ efflux from synaptosomal mitochondria.
AB  - The effects of gonadal steroid hormone, 17beta-estradiol (E2), in vitro on rat
      brain mitochondria Ca2+ movement were investigated. Intrasynaptosomal
      mitochondria Ca2+ uptake via an energy-driven Ca2+ uniporter have Km = 112.73 +/-
      7.3 micromol x l(-1) and Vmax = 21.97 +/- 1.7 nmol 45Ca2+ mg(-1). Ca2+ release
      trough a Na+/Ca2+ antiporter was measured with a Km for Na+ of 43.7 +/- 2.6 mmol
      x l(-1), and Vmax of 1.5 +/- 0.3 nmol 45Ca2+ mg(-1). Addition of estradiol in
      preincubation mixture did not affect the uptake of Ca2+ mediated by the ruthenium
      red-sensitive uniporter, while it produced biphasic effect on Na-dependent Ca2+
      efflux. Estradiol at concentrations up to 1 nmol x l(-1) decreased the efflux
      significantly (63% inhibition with respect to the control), and at concentrations
      above 10 nmol x l(-1) increased it exponentially. The maximum inhibiting
      concentration of estradiol (0.5 nmol x l(-1)) increased the affinity of the
      uniporter (Km reduced by about 30%), without affecting significantly the capacity
      (Vmax) for Na+. The results presented suggest that estradiol inhibits Na
      dependent Ca2+ efflux from mitochondria and acts on mitochondrial retention of
      Ca2+, which may modulate mitochondrial and consequently synaptosomal content of
      Ca2+, and in this way exerts its role in the homeostasis of calcium in nerve
      terminals.

PMID- 10930140
TI  - Interaction of acetochlor with estrogen receptor in the rat uterus. Acetochlor-
      possible endocrine modulator?
AB  - The aim of the present study was to investigate the ability of the
      chloroacetanilide herbicide acetochlor to interact with the endocrine system. The
      modulation of the binding of [3H]estradiol-17beta to protamine sulphate
      precipitated uterine nuclear and cytoplasmic estrogen receptors was analysed for
      this purpose. Two different stages of reproductive life cycle of female rats,
      virgin and uniparous, were used. Our results demonstrate that acetochlor
      interacts in a specific manner with high-affinity limited-capacity uterine
      estrogen receptors. A significant difference (p < 0.001) in estrogen receptor
      density was observed between two control groups: uniparous rats (Bmax = 43.634 +/
      9.516) and virgin rats (Bmax = 154.375 +/- 21.462), suggesting an intrinsic
      difference in the nuclear estrogen receptor levels between female rats in
      different reproductive life cycle stages. Consequently, a different response to
      acetochlor treatment was noted. Exposure to acetochlor significantly (p < 0.001)
      increased estrogen receptor binding activity in the nuclear fraction of uniparous
      female rats (Bmax = 123.324 +/- 5.666) in comparison to control (Bmax = 43.634 +/
      9.516). In exposed virgin female rats, no significant difference was detected
      when compared to the corresponding control group. These results should prompt us
      to more thoroughly evaluate potential hazards of acetochlor to human and wildlife
      endocrine systems.

PMID- 10930141
TI  - Association of lysozyme with phospholipid vesicles is accompanied by membrane
      surface dehydration.
AB  - Lysozyme is a globular protein which is known to bind to negatively charged
      phospholipid vesicles. In order to study the relationship between binding of the
      protein and the subsequent destabilization of the phospholipid vesicles a set of
      experiments was performed using phospholipid monolayers and vesicles. Using
      microelectrophoresis the binding of lysozyme to phospholipid vesicles made of PS
      was determined. At low ionic strength and mild acidic pH of the solution lysozyme
      reduced the magnitude of the negative zeta potential of PS vesicles at lower
      concentrations compared to neutral pH and high ionic strength. In contrast, the
      bound fraction of lysozyme to PS vesicles was nearly constant at acidic and
      neutral pH. At low pH, the binding of lysozyme was accompanied by a strong
      aggregation of the vesicles. Lysozyme binding to PS vesicles is accompanied by
      its penetration into the PL monolayer. This was measured by surface tension and
      film balance measurements at low pH and low ionic strength. The interaction of
      lysozyme with negatively charged vesicles lead to a decrease of the vesicle
      surface hydration as measured by the shift of the emission peak of the
      fluorescent probe DPE. The binding of bis-ANS increased at low pH after addition
      of lysozyme to the vesicles. This indicates that more hydrophobic patches of the
      lysozyme-PS complex are exposed at low pH. At low pH the binding process of
      lysozyme to PS vesicles was followed by an extensive intermixing of phospholipids
      between the aggregated vesicles, accompanied by a massive leakage of the aqueous
      content of vesicles.

PMID- 10930142
TI  - Relationships between serum levels of autoantibodies against oxidized low density
      lipoproteins, lipid-soluble antioxidants and apolipoprotein B in patients with
      coronary heart disease.
AB  - High affinity IgG autoantibodies against oxidized low density lipoproteins
      (oxLDLs), apolipoprotein B and lipid-soluble antioxidants--alpha-tocopherol and
      beta-carotene, were tested in patients with coronary heart disease. Correlation
      relationships between these parameters were analysed. Fifty one patients with
      coronary heart disease (37 males/14 females) defined as Q-wave myocardial
      infarction and/or stenosis of more than 50%, and 51 healthy blood donors (34
      males/17 females) as controls participated in this study. LDLs were isolated by
      density gradient ultracentrifugation and oxidized with Cu2+. OxLDLs or native
      LDLs (nLDLs) were used as antigens in enzyme immunoassay (ELISA) to detect IgG
      autoantibodies in the serum. The contents of alpha-tocopherol and beta-carotene
      were measured by HPLC. Apolipoprotein B was determined by immunoturbidimetry.
      Correlation analysis of the parameters was carried out by Spearmann's test. Alpha
      tocopherol was decreased significantly in the serum of patients with coronary
      heart disease (2.96+/-1.63 nmol/mg serum protein vs 6.23+/-2.28 nmol/mg serum
      protein in Control group) (p < 0.01). Also, the serum level of beta-carotene was
      decreased in patients with coronary heart disease (174.0+/-95.7 pmol/mg serum
      protein vs 313.2+/-141.5 pmol/mg serum protein in Control group) (p < 0.01),
      while apolipoprotein B was increased significantly (1.20+/-0.34 g/l in patients
      with coronary heart disease vs 0.86+/-0.23 g/l in Control group) (p < 0.001). In
      a previous study we established that the mean serum level of IgG autoantibodies
      against oxLDLs (expressed in optical density units) was about 2.5 times higher in
      patients with coronary heart disease as compared to control subjects (p < 0.001).
      A good positive linear correlation was observed between alpha-tocopherol and
      apolipoprotein B levels in Control group (r = 0.78, p < 0.001), as well as in the
      group of patients with coronary heart disease (r = 0.42, p < 0.001). Poor
      nonsignificant correlations were established between all another measured
      parameters. In conclusion, the lipid-soluble antioxidants--alpha-tocopherol and
      beta-carotene, are not informative with respect to the susceptibility of the
      serum to oxidative modifications and as to the extent of the subsequent humoral
      immune response. Presumably, the reduction of the correlation coefficient between
      apolipoprotein-B and alpha-tocopherol in patients with coronary heart disease in
      comparison with control subjects could provide indirect information on
      modifications of apolipoprotein-B and on a decrease of its susceptibility to
      interact with this major lipid-soluble antioxidant in atherogenesis.

PMID- 10930143
TI  - Lipopolysaccharide-induced HIV-1 expression in transgenic mice is mediated by
      tumor necrosis factor-alpha and interleukin-1, but not by interferon-gamma nor
      interleukin-6.
AB  - BACKGROUND: As serum HIV-1 load correlates well with the prognosis of the
      disease, it is suggested that the viral load is one of the major determinants of
      the disease progression of AIDS. Accordingly, HIV-1 activation mechanisms were
      extensively studied in vitro, and involvement of cytokines including tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6 and interferon (IFN)-gamma
      has been suggested in this process. However, so far the roles of these cytokines
      in the HIV-1 expression in vivo have not been well elucidated because of the lack
      of appropriate animal disease models. OBJECTIVE: To elucidate the roles of
      cytokines in HIV-1 activation in vivo. DESIGN AND METHODS: Transgenic mice
      carrying a defective HIV-1 genome were used as a model for HIV-1 carriers. In
      order to examine the possible involvement of cytokines in HIV-1 expression, TNF
      alpha-, IL-1-, IL-6- and IFN-gamma-deficient HIV-1 transgenic mice, were produced
      and HIV-1 expression was analyzed after activation with bacterial
      lipopolysaccharides (LPS). RESULTS: HIV-1 expression in the transgenic mouse
      spleen was activated 10- to 20-fold by LPS, and the serum p24 Gag protein levels
      reached 400 pg/ml, which is nearly equal to the levels that occur in AIDS
      patients. However, this augmentation was suppressed by 60% in TNF-alpha-deficient
      mice and by 40% in IL-1alpha/beta-deficient mice. In contrast, no suppression was
      observed in either IL-6-, IFN-gamma-, IL-1alpha, or IL-1beta-deficient mice.
      CONCLUSIONS: Results suggest that TNF-alpha and IL-1 play important roles in HIV
      1 gene activation and selective suppression of these cytokines could improve
      clinical prognosis and potentially slow progression of the disease.

PMID- 10930144
TI  - Contribution of nucleoside analogue reverse transcriptase inhibitors to
      subcutaneous fat wasting in patients with HIV infection.
AB  - BACKGROUND: Progressive subcutaneous fat wasting, fat accumulation, dyslipidaemia
      and insulin resistance in HIV-infected patients on antiretroviral therapy has
      been attributed to the long-term toxicity of HIV protease inhibitors (PI). More
      recently, fat wasting has been observed in patients who have never taken a PI,
      implicating an independent effect of nucleoside analogue reverse transcriptase
      inhibitor (NRTI) therapy. OBJECTIVES: To determine the relative contribution of
      NRTI and PI, as well as any other factors, to fat wasting in HIV-infected
      patients. DESIGN: Longitudinal cohort study involving 277 participants of the
      Western Australian HIV Cohort Study. METHODS: The time to onset of clinically
      apparent fat wasting in patients receiving different antiretroviral regimens was
      compared using standardized clinical criteria. Regional fat measured by dual
      energy X-ray absorptiometry (DEXA) in 161 patients was also compared. The average
      rate of percentage fat reduction was estimated in 70 patients who had consecutive
      DEXA scans at approximately 6-monthly intervals. Multiple confounding factors
      were considered in the analyses. RESULTS: Progressive subcutaneous fat wasting,
      indistinguishable from that described in PI-treated patients, does occur in PI
      naive, NRTI-treated patients. In patients taking triple combination
      antiretroviral therapy, age (relative risk = 1.052 per year; P < 0.0001), white
      race (relative risk = 3.9; P = 0.023), longer duration of dual NRTI therapy prior
      to addition of PI (relative risk = 1.021 per month; P = 0.0046) and increased
      cumulative time on stavudine-containing regimens compared with time on zidovudine
      containing regimens (relative risk = 1.085 per month; P < 0.0001) are associated
      with increased risk of fat wasting. Stavudine increases the risk of fat wasting
      by 265% per year compared with zidovudine. However PI therapy is associated with
      faster progression to clinically apparent wasting compared with dual NRTI therapy
      without PI. The results of DEXA scanning supports these clinical data and suggest
      a non-linear decline in fat over time. CONCLUSIONS: NRTIs do have an independent
      contribution to fat wasting, but PI are the predominant influence and may act
      synergistically with NRTIs. NRTIs appear to predispose individuals to slowly
      progressive fat loss, which is markedly accelerated when a PI and NRTIs are
      combined. Of the NRTIs, stavudine leads to an earlier onset of clinically
      apparent fat wasting compared with zidovudine. Fat wasting associated with NRTI
      use may be a manifestation of mitochondrial toxicity, which may be exacerbated by
      PI use.

PMID- 10930145
TI  - Effect of cytokines on HIV-induced depletion of thymocytes in vivo.
AB  - BACKGROUND: Cytokines play an important role in the differentiation of thymocytes
      into mature T cells; consequently, certain cytokines could be useful for immune
      reconstitution after HIV infection without increasing viral load. OBJECTIVE: To
      investigate whether cytokines affect immune depletion caused by HIV infection
      with a CXCR4-tropic strain in SCID-hu mice implanted with human fetal thymus and
      liver (thy/liv) tissue. METHODS: The thy/liv implants were either mock infected
      or infected with HIV-1 NL4-3, a CXCR4-tropic molecular clone. Interleukin (IL)-2,
      IL-4, IL-7, interferon-gamma (IFN-gamma) or diluent was administered to the mice
      during the second and third week postinfection. Viral load and immunophenotype
      were determined in thymocytes. RESULTS: Thymocyte subset distributions at 3 weeks
      postinfection were significantly influenced by treatment with certain cytokines.
      In particular, IL-2 caused the infected mice to retain a thymocyte profile that
      was more similar to that in mock-infected mice than that in diluent-treated
      infected mice, in that the percentages of immature CD4+CD8+ and CD5+CD1+ cells
      were slightly higher and much less variable than in diluent-treated infected
      mice. The effect of IFN-gamma treatment was similar to IL-2 but did not reach
      statistical significance. However, after IFN-gamma treatment, normal percentages
      of mature CD3+CD69+ cells were maintained whereas this population was relatively
      increased in diluent-treated infected mice. Although treatment with IL-4 and IL-7
      delayed depletion of immature thymocytes, these cytokines increased viral load.
      CONCLUSIONS: Cytokines such as IL-2 and IFN-gamma maintain immature thymocytes
      without increasing viral load and may be useful as adjuncts to improve immune
      reconstitution after HIV infection.

PMID- 10930146
TI  - Neurocognitive and psychological contributions to quality of life in HIV-1
      infected women.
AB  - OBJECTIVES: The purpose of this study was to examine the impact of neurocognitive
      and emotional distress and immune system dysfunction on quality of life in women
      with HIV. METHODS: Thirty-six HIV-seropositive women were administered measures
      of mood status (Profile of Mood States), quality of life (Multidimensional
      Quality of Life Questionnaire for Persons with HIV) and cognitive function. CD4
      cell counts were obtained as an indicator of immune system status. RESULTS:
      Regression analyses revealed that independent of severity of emotional distress,
      neurocognitive deficits on measures of executive control and speed of information
      processing were associated with reduced quality of life. Emotional status also
      was associated with quality of life and together with neurocognitive performance
      accounted for most of the variance associated with quality of life. Reduced CD4
      cell count was significantly associated with neurocognitive deficits, but not
      severity of emotional distress or quality of life. CONCLUSIONS: Quality of life
      among women who are infected with HIV is strongly influenced by both
      neurocognitive and emotional status, as women with the greatest neurocognitive
      impairment and emotional distress report the poorest quality of life.

PMID- 10930147
TI  - Importance of protease inhibitor plasma levels in HIV-infected patients treated
      with genotypic-guided therapy: pharmacological data from the Viradapt Study.
AB  - OBJECTIVE: In a prospective randomized study, the impact of plasma protease
      inhibitor (PI) trough levels on changes in HIV RNA were assessed in patients
      treated with genotypic-guided therapy. METHODS: Patients failing combination
      therapy (HIV-1 RNA > 10,000 copies/ml, and at least 6 months of therapy with
      nucleoside analogues and 3 months with PI) were randomly assigned into two arms:
      control group (C) in which the treatment was modified according to the standard
      of care; genotypic group (G) in which the treatment was modified according to
      resistance mutation profiles. Serial PI plasma levels were performed in patients
      throughout the 12 month study. PI levels were determined by high performance
      liquid chromatography. 'Suboptimal' concentration (SOC) was defined as at least
      two PI plasma levels below 2 x IC95. Others were defined as 'optimal'
      concentration (OC). Patients were categorized into four groups: G1 (SOC/control);
      G2 (OC/control); G3 (SOC/genotype); G4 (OC/genotype). An intent-to-treat analysis
      was performed with viral load as the primary endpoint. RESULTS: A total of 81
      patients [mean age 39.7 +/- 8 years, 59 men, 52.7% Centers for Disease Control
      and Prevention (CDC) stage C] were included in the pharmacological substudy. The
      two groups according to randomization arms were comparable in terms of risk
      factor, age, sex, previous treatments, baseline CD4 cell count, HIV-1 RNA and
      mean PI plasma concentrations. Linear regression analysis showed a significant
      relationship between PI concentration and HIV RNA in the plasma. OC and SOC were
      found in 67.9% (55/81) and 32.1% (26/81) of patients, respectively. Mean changes
      in HIV RNA from baseline at month 6 were: -0.23 +/- 0.29 log10 copies/ml (G1); 
      0.97 +/- 0.28 (G2); -0.68 +/- 0.37 (G3); -1.38 +/- 0.20 (G4). Multivariate
      analysis showed PI plasma concentrations to be an independent predictor of HIV
      RNA evolution (P = 0.017). CONCLUSION: Multiple parameters determine the response
      to antiretroviral therapy and causes other than the development of drug
      resistance should be considered in the setting of therapeutic failure. Suboptimal
      concentrations of PI limit the response to antiretroviral therapy. Therapeutic
      drug monitoring of the PI plasma concentration may therefore prove useful in
      optimizing antiretroviral therapy.

PMID- 10930148
TI  - Trial of oral fumagillin for the treatment of intestinal microsporidiosis in
      patients with HIV infection. ANRS 054 Study Group. Agence Nationale de Recherche
      sur le SIDA.
AB  - OBJECTIVE: Intestinal microsporidiosis caused by Enterocytozoon bieneusi is a
      cause of chronic diarrhoea in patients with HIV infection for which there is no
      current therapy. This study was designed to assess the safety and efficacy of
      oral fumagillin in this infection. DESIGN: A dose-escalation trial. METHODS:
      Twenty-nine HIV-infected patients with E. bieneusi infection were consecutively
      enrolled in the trial. Oral doses of fumagillin were given to four groups of
      patients for 14 days: 10 mg/day (group 1), 20 mg/day (group 2), 40 mg/day (group
      3), and 60 mg/day (group 4). Patients were seen at weeks 1, 2, 4 and 6 to assess
      safety and efficacy. Efficacy was assessed primarily by the clearance of
      microsporidia from stools and follow-up duodenal biopsies. RESULTS: Thirteen
      patients complained of abdominal cramps, vomiting or diarrhoea during the study,
      and three patients had fumagillin withdrawn because of adverse events.
      Thrombocytopenia, neutropenia and hyperlipasaemia were the most frequent
      biological adverse events. Twenty-one out of 29 patients transiently cleared
      microsporidia from their stools during the study. By week 6, however, all
      patients in groups 1, 2 and 3 had parasitic relapse. Interestingly, eight out of
      11 (72%) patients treated with 60 mg/day (group 4) apparently cleared
      microsporidia from their gastrointestinal tract and gained weight. No parasitic
      relapse was documented in these eight patients during a mean follow-up of 11.5
      months. CONCLUSION: Treatment with fumagillin at 60 mg/day for 14 days has
      promise as an effective oral treatment for E. bieneusi infections.

PMID- 10930149
TI  - A randomized, double-blind trial of half versus standard dose of zidovudine plus
      zalcitabine in Thai HIV-1-infected patients (study HIV-NAT 001). HIV Netherlands
      Australia Thailand Research Collaboration.
AB  - BACKGROUND: Triple combination antiretroviral therapy, recommended as standard of
      care, is unaffordable for much of the developing world. OBJECTIVES: To establish
      whether half doses of zidovudine (AZT) and zalcitabine (ddC) are as effective as
      standard doses in a Thai population with lower body weight than Western
      populations and predominantly infected with HIV-1 subtype E. METHODS: A group of
      116 antiretroviral naive patients, with CD4 cell counts 100-500 x 10(6) cells/l,
      were randomized to: AZT 200 mg three times daily plus ddC 0.75 mg three times
      daily versus AZT 100 mg three times daily plus ddC 0.375 mg three times daily and
      followed-up regularly for 48 weeks. RESULTS: The study enrolled 111 patients: 59
      men and 52 women, body weight (mean +/- standard deviation) 56.4 +/- 12.3 kg,
      mean CD4 cell count 324 x 10(6) cells/l, mean HIV RNA 4.7 log10 copies/ml. There
      were no significant differences between the two groups. Twelve patients
      discontinued, including two deaths that were unrelated to study medication. No
      significant differences in adverse events were seen. Week 48 data for the
      standard dose and half dose arms, respectively, were mean CD4 cell count
      increases of 52 and 78 x 10(6) cells/l (P = 0.34), mean plasma HIV-1 RNA
      reduction of 1.4 and 1.1 log10 copies/ml (P = 0.10), HIV RNA of < 400 copies/ml
      in 52 and 20%[ (P = 0.001). Participants with higher than mean baseline CD8 cell
      counts (mean 1062 x 10(6) cells/l) showed greater decline in CD8 cells on
      standard doses. Further analysis showed improved reduction in HIV RNA (P <
      0.0001) and in the percentage with undetectable HIV RNA (P = 0.0137) in the
      standard dose arm, corrected for baseline HIV RNA, which if < 4.75 log10
      copies/ml significantly correlated with HIV RNA < 400 copies/ml at week 48.
      CONCLUSION: At week 48, the proportion with HIV RNA < 400 copies/ml was
      significantly higher in the standard dose arm; lower baseline HIV RNA correlated
      with better HIV RNA outcome at 48 weeks. The arms did not differ in CD4 cell
      response but standard doses correlated with greater CD8 cell decline.

PMID- 10930150
TI  - Pre-HAART HIV burden approximates post-HAART viral levels following interruption
      of therapy in patients with sustained viral suppression.
AB  - OBJECTIVE: To evaluate the relationship between the HIV viral burden in
      individuals prior to receiving highly-active antiretroviral therapy (HAART) and
      the viral burden after withdrawal of HAART. DESIGN AND SETTING: Retrospective
      cohort study at the National Institutes of Health, Bethesda, Maryland, USA.
      PATIENTS: Fourteen HIV-infected patients who achieved and maintained viral
      control on HAART who subsequently discontinued HAART. MAIN OUTCOME MEASURES: Pre-
      and post-HAART viral loads measured from plasma or serum. RESULTS: Patients
      achieved viral control (< 500 copies/ml) on HAART in a median 28 days (range, 15
      490 days; mean, 72 days), maintained viral control for a median 661 days (range,
      53-1067 days; mean, 611 days), and subsequently discontinued HAART for a median
      49 days (range, 14-196 days; mean, 73 days). The median difference between the
      pre- and post-HAART viral loads was 0.16 log10 (range, -0.72 to 1.05 log10; mean,
      0.19 log10). The median absolute difference between the pre- and post-HAART viral
      loads was 0.43 log10 (range, 0.06-1.05 log10; mean, 0.46 log10). Nine individuals
      had post-HAART values higher than pre-HAART values, five had lower values. Median
      duration between pre- and post-HAART viral load measurements was 1757 days
      (range, 117-3177 days; mean, 1756 days), or 4.8 years. CONCLUSIONS: After
      discontinuing HAART, individuals had rebounds in their viral burdens
      approximating pre-HAART levels, even after a significant lapse of time
      approaching 5 years. Our data suggest that an intrinsic viral load set-point may
      exist, and that a single interruption of an effective regimen with viral
      suppression for almost 2 years does not significantly alter this set-point.

PMID- 10930151
TI  - Cytokine profiles in seronegative volunteers immunized with a recombinant
      canarypox and gp120 prime-boost HIV-1 vaccine. NIAID AIDS Vaccine Evaluation
      Group.
AB  - OBJECTIVES: To study memory T cell proliferative responses and cytokine profiles
      induced in HIV-1 seronegative volunteers immunized with a live recombinant
      canarypox vector expressing HIV-1 antigens (ALVAC-HIV) and boosted with a
      recombinant gp120 subunit vaccine. DESIGN: HIV-specific T cell proliferative
      responses and cytokines were measured 2 weeks after vaccination. Cytokines
      secreted by T helper 1 cells (Th1) [interleukin (IL)-2 and interferon-gamma (IFN
      gamma)] and T helper 2 (Th2) cells (IL-4, IL-5, IL-6, and IL-10) were assessed
      both at the mRNA and the protein level. METHODS: Peripheral blood mononuclear
      cells (PBMC) were stimulated in vitro with HIV antigens. Subsequently, T cell
      proliferation was measured in a standard lymphoproliferation assay; secreted
      cytokines were measured using an enzyme-linked immunosorbent assay and
      upregulation of cytokine mRNA was measured using reverse transcriptase polymerase
      chain reaction. RESULTS: All individuals who had received ALVAC-HIV followed by
      the protein vaccine exhibited HIV-1-specific T cell proliferative responses.
      Moreover, the PBMC of all prime-boost vaccinated individuals produced detectable
      IFN-gamma and IL-10 in response to stimulation with HIV-1 envelope glycoprotein
      antigens; 83% also had detectable levels of IL-2 and IL-6, 71% had detectable
      levels of IL-4, and 86% had detectable levels of IL-5. CONCLUSIONS: These data
      indicate that this vaccination regimen was inducing both Th1- and Th2-type
      responses to HIV-1 envelope antigens. This prime-boost vaccination approach
      elicited T cell help for the generation of cytotoxic T lymphocyte responses as
      well as help for antibody production and so promises to generate a broad HIV-1
      specific immune response.

PMID- 10930152
TI  - A randomized, dose-finding study with didanosine plus stavudine versus didanosine
      alone in antiviral-naive, HIV-infected Thai patients.
AB  - OBJECTIVES: To evaluate the safety and efficacy of four different regimens of
      didanosine (ddI) + stavudine (d4T) in HIV-infected Thais. DESIGN: Prospective,
      open-label, randomized study. METHODS: Patients were randomized to four regimens
      of high and low doses of ddI and d4T or to ddI alone. D4T was added to the ddI
      alone arm after week 24. The duration of study was 48 weeks. RESULTS: Seventy
      eight patients were randomized (mean CD4 cell count, 255 x 10(6)/l; mean plasma
      HIV-1 RNA; 4.3 log10 copies/ml). In the intent-to-treat analysis, 78% of patients
      in the pooled combination arms and 20% of the patients in the ddI alone arm (to
      which d4T was added after 24 weeks) showed plasma HIV-1 RNA < 500 copies/ml at
      week 24 (P < 0.001), and 59% versus 53% at week 48, respectively. In addition,
      the proportion of patients with < 50 HIV-1 RNA copies/ml was 13% versus 7% at
      week 24 (P = 0.5) and 17% versus 20% at week 48 respectively. At week 24, median
      CD4 cell count increases from baseline were 101 x 10(6)/l in the pooled
      combination versus 76 x 10(6)/l in the ddI alone arm (P = 0.78). Logistic
      regression modeling suggested a correlation between receiving high dose ddI and
      achieving HIV-1 RNA < 500 copies/ml at week 48 (P = 0.07). CONCLUSIONS: The
      d4T/ddI combination was superior to ddI alone in producing HIV-1 viral
      suppression. At week 48, > 60% of patients treated with this combination reached
      HIV-1 RNA levels < 500 copies/ml. Receiving high dose ddI but not d4T may
      correlate with a better viral suppression.

PMID- 10930153
TI  - Highly active antiretroviral therapy including protease inhibitors does not
      confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.
AB  - OBJECTIVE: To determine if triple combination therapy, particularly including HIV
      protease inhibitors (PI), confers an unique immunological benefit that is
      independent of reductions of plasma viral load (pVL). DESIGN: The correlation
      between changes from baseline in CD4 cell count and pVL was examined at all time
      points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and
      INCAS) that compared dual nucleoside therapy with triple combination therapy.
      METHODS: Individual pVL and CD4 cell counts changes from baseline were entered
      into multivariate linear regression models for patients receiving double therapy
      and for those receiving triple therapy including a PI and/or a non-nucleoside
      reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested.
      RESULTS: After 52 weeks of therapy, the relationship between changes from
      baseline CD4 cell count and pVL was independent of whether patients were assigned
      double or triple therapy (P = 0.23 and 0.69 for intercept and slope,
      respectively), or whether patients were assigned triple therapy including a PI or
      triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5%
      of patients ever had 'discordant' increases in both CD4 cell count and pVL
      compared with baseline, and this proportion was unrelated to the class of therapy
      used. 'Discordant' decreases from baseline in both parameters were observed in up
      to 35% of individuals. The correlation between pVL and CD4 cell count changes
      from baseline improved over time on therapy, regardless of the therapeutic
      regimen involved. CONCLUSIONS: The data provide no evidence for a CD4 cell count
      benefit of highly active antiretroviral therapy (HAART) unique to triple therapy
      or PI-containing regimens.

PMID- 10930154
TI  - Risk factors for preterm birth, low birth weight, and intrauterine growth
      retardation in infants born to HIV-infected pregnant women receiving zidovudine.
      Pediatric AIDS Clinical Trials Group 185 Team.
AB  - OBJECTIVE: To evaluate independent contributions of maternal factors to adverse
      pregnancy outcomes (APO) in HIV-infected women receiving antiretroviral therapy
      (ART). DESIGN: Risk factors for preterm birth (< 37 weeks gestation), low birth
      weight (LBW) (< 2500 g), and intrauterine growth retardation (IUGR) (birth weight
      < 10th percentile for gestational age) examined in 497 HIV-infected pregnant
      women enrolled in PACTG 185, a perinatal clinical trial. METHODS: HIV RNA copy
      number, culture titer, and CD4 lymphocyte counts were measured during pregnancy.
      Information collected included antenatal use of cigarettes, alcohol, illicit
      drugs; ART; obstetric history and complications. RESULTS: Eighty-six percent were
      minority race/ethnicity; 86% received antenatal monotherapy, predominantly
      zidovudine (ZDV), and 14% received combination antiretrovirals. Preterm birth
      occurred in 17%, LBW in 13%, IUGR in 6%. Risk of preterm birth was independently
      associated with prior preterm birth [odds ratio (OR) 3.34; P < 0.001], multiple
      gestation (OR, 6.02; P = 0.011), antenatal alcohol use (OR, 1.91; P = 0.038), and
      antenatal diagnosis of genital herpes (OR, 0.24; P = 0.022) or pre-eclampsia (OR,
      6.36; P = 0.025). LBW was associated with antenatal diagnosis of genital herpes
      (OR, 0.08; P = 0.014) and pre-eclampsia (OR, 5.25; P = 0.049), and baseline HIV
      culture titer (OR, 1.41; P = 0.037). IUGR was associated with multiple gestation
      (OR, 8.20; P = 0.010), antenatal cigarette use (OR, 3.60; P = 0.008), and pre
      eclampsia (OR, 12.90; P = 0.007). Maternal immune status and HIV RNA copy number
      were not associated with APO. CONCLUSIONS: Risk factors for APO in antiretroviral
      treated HIV-infected women are similar to those reported for uninfected women.
      These data suggest that provision of prenatal care and ART may reduce APO.

PMID- 10930155
TI  - Impact of HIV infection on meningitis in Harare, Zimbabwe: a prospective study of
      406 predominantly adult patients.
AB  - OBJECTIVE: To determine the causative organisms and characteristics of patients
      presenting with features of meningitis. DESIGN: A prospective cross-sectional
      study. SETTING: Two tertiary university-affiliated hospitals in Harare, Zimbabwe.
      PATIENTS: Four-hundred and six patients clinically suspected to have meningitis.
      MAIN OUTCOME MEASURES: Causative organisms of meningitis; clinical and
      cerebrospinal fluid characteristics. RESULTS: Four-hundred and six predominantly
      adult (95% were aged > or = 18 years) patients were suspected to have meningitis.
      Of the 200 patients confirmed to have meningitis, 89 (45%) had cryptococcal
      meningitis (CM), 54 (27%) had mononuclear meningitis (MM), 31 (16%) had pyogenic
      meningitis (PM), 24 (12%) had tuberculous meningitis (TBM) and 2 (1%) had
      undefined meningitis. HIV seropositivity was 100% in CM, 83% in MM, 81% in PM and
      88% in TBM patients. In-hospital mortality rate was 38.8% for CM, 34.9% for MM,
      68% for PM and 66.7% for TBM. HIV seropositivity was 80% in the 206 patients not
      found to have meningitis. CONCLUSIONS: All patients suspected to have meningitis
      had a high HIV sero positivity irrespective of whether they were later confirmed
      to have meningitis or not. CM was the most common type of meningitis seen. In
      hospital mortality was high irrespective of the cause of meningitis.

PMID- 10930156
TI  - Discontinuing or withholding primary prophylaxis against Mycobacterium avium in
      patients on successful antiretroviral combination therapy. The Swiss HIV Cohort
      Study.
AB  - OBJECTIVE: To assess the safety of discontinuing or withholding primary
      prophylaxis against disseminated Mycobacterium avium infection (MAC) in HIV
      infected patients on successful antiretroviral combination therapy. SETTING:
      National prospective multicentre cohort study. DESIGN: HIV-infected patients were
      eligible for the analysis if: (i) they had a history of at least two CD4 cell
      counts < 50 x 10(6)/l; (ii) they had never had MAC; (iii) they had discontinued
      or never begun primary prophylaxis against MAC; (iv) they received antiretroviral
      therapy and demonstrated an increase in CD4 cell counts to > or = 100 x 10(6)/l
      that was sustained for at least 12 weeks. From this time point until last follow
      up, incidence of disseminated MAC disease was measured, and 99% confidence
      intervals were calculated assuming a Poisson distribution of events. RESULTS: Two
      hundred and fifty-three patients (22.5% female; median age, 37 years, 30%
      injecting drug users) were eligible for analysis. Sixty-six per cent were in
      Centers for Disease Control and Prevention (CDC) stage C, and 28% were in CDC
      stage B. Their median nadir CD4 cell count was 10 x 10(6)/l, the median duration
      of CD4 cell count < 50 x 10(6)/l was 12 months. During a total follow-up of 364.3
      patient-years there was no case of disseminated MAC. The one-sided 99% confidence
      limit for incidence density of MAC was 1.3 per 100 person-years. CONCLUSION:
      Discontinuing or withholding primary prophylaxis against MAC is safe in patients
      who have a sustained increase in their CD4 cell count to > or = 100 x 10(6)/l.

PMID- 10930157
TI  - High AIDS awareness may cause tuberculosis patient delay: results from an HIV
      epidemic area, Thailand.
AB  - OBJECTIVE: To elicit community perceptions about tuberculosis (TB) and the
      behaviour of TB patients in an area where significant public health attention has
      been focused on AIDS. SETTING: Chiang Rai, Thailand, the epicentre of HIV/AIDS in
      this country. DESIGN: Eleven focus group sessions with a cross-section of the
      population. PARTICIPANTS: Health centre staff, community members, persons having
      HIV, TB patients (with and without HIV infection), and male injecting drug users;
      five female groups and six male groups. RESULT: People had good knowledge of AIDS
      but they knew little about TB. Only a few female patients, whose husbands had
      died of TB and AIDS, recognized their symptoms as TB and immediately sought care.
      People defined persons losing weight, having fever and cough as AIDS rather than
      TB. This resulted in delay in seeking care and non-adherence to TB treatment in
      some patients who suspected they had AIDS, and feared AIDS detection. Most HIV
      negative TB patients were also suspected by their relatives and neighbours of
      having AIDS. Most participants, except HIV-positive females, believed TB to be
      curable. Although less than AIDS, the community stigmatized TB patients because
      of it being contagious and easily transmitted through exhalations, foods and
      drinks and closeness to TB patients. CONCLUSION: In HIV/AIDS high endemic
      situation, increased awareness and stigmatization of AIDS and inadequate
      knowledge of TB can result in delay in seeking TB care and in treatment non
      adherence.

PMID- 10930158
TI  - Interventions to prevent vertical transmission of HIV-1: effect on viral
      detection rate in early infant samples.
AB  - OBJECTIVE: To determine whether mode of delivery or the use of maternal or
      neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be
      detected in infected infants, particularly the probability of detection at birth.
      METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1
      infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14
      days of age were analysed. Weibull mixture models were used to estimate the
      cumulative proportion of infants with detectable levels of HIV-1 according to use
      of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and
      mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were
      first tested, at a median age of 2 days. At birth, it was estimated that 36% [95%
      confidence interval (CI), 31-41%] of infants have levels of virus that can be
      detected by DNA PCR or cell culture. This percentage was not associated with
      either mode of delivery (35% for vaginal delivery versus 40% for cesarean section
      delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis.
      Among infants with undetectable levels of HIV-1 at birth, the median time to
      viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This
      time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were
      exposed to antiretroviral therapy postnatally compared with infants who were not
      exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of
      an early virological test for HIV-1 is thought to be related directly to the
      timing of transmission and cesarean section delivery primarily reduces the risk
      of intrapartum transmission. The absence of an association between mode of
      delivery and viral detectability at birth was therefore unexpected. There was no
      evidence that foetal or neonatal exposure to prophylactic zidovudine delays
      substantially the diagnosis of infection, although this cannot be inferred for
      combination antiretroviral therapy.

PMID- 10930159
TI  - Syndromic treatment of sexually transmitted diseases reduces the proportion of
      incident HIV infections attributable to these diseases in rural Tanzania.
AB  - OBJECTIVES: To compare the proportion of HIV seroconversions attributable to
      other sexually transmitted diseases in the intervention and comparison arms of
      the Mwanza sexually transmitted diseases (STD) intervention trial. DESIGN: Case
      control study of 96 cases of HIV seroconversion and 974 HIV-negative controls,
      nested within the Mwanza trial cohort. METHODS: Data on reported STD symptoms
      during 2 years of follow-up, and serological evidence of recent syphilis, were
      used to obtain odds ratios (ORs) for HIV seroconversion, adjusted for community,
      age, marital status, sex partners and travel. Population-attributable fractions
      (PAF) of HIV seroconversions associated with these STD exposures were calculated
      separately for the intervention and comparison arms, and for men and women.
      RESULTS: In men in the comparison arm, adjusted ORs for ulcers (14.8), discharge
      (3.3), any symptom (4.1) and any STD (4.0) were highly significant. There were no
      significant associations between HIV incidence and STD exposures in the
      intervention arm. The PAF were consistently higher in the comparison arm than the
      intervention arm. In men, the PAF for any STD was 39.6% [95% confidence interval
      (CI), 12.4-58.3)] in the comparison arm but only 12.0% (CI, 0.0-35.9) in the
      intervention arm. The PAF for women were lower than for men. CONCLUSIONS: These
      are minimal PAF estimates and they do not account for STD effects on HIV
      infectiousness. Nevertheless, a substantial proportion of new HIV infections in
      men in the comparison arm were attributable to STD. Lower PAF in the intervention
      arm than in the comparison arm for men provide further evidence of the role of
      STD cofactors in HIV transmission, supporting the hypothesis that the Mwanza
      intervention reduced the duration of symptomatic STD, thus reducing the HIV risk
      associated with such STD.

PMID- 10930160
TI  - Evaluating changes in health status in HIV-infected patients: Medical Outcomes
      Study-HIV and Multidimensional Quality of Life-HIV quality of life
      questionnaires. Spanish MOS-HIV and MQOL-HIV Validation Group.
AB  - OBJECTIVE: To compare the sensitivity to change of two HIV-health-related quality
      of life (HRQoL) questionnaires--the Medical Outcomes Study (MOS-HIV) and
      Multidimensional Quality of Life (MQOL-HIV) for use in clinical research.
      METHODS: A sample of 296 HIV-infected patients starting or switching
      antiretroviral treatment were randomly assigned either the MOS-HIV or MQOL-HIV
      questionnaires at baseline and after 3 months of treatment. Ceiling and floor
      effects were evaluated. Sensitivity to change was assessed by comparing the
      percentage of dimensions with statistically significant pre-post-treatment
      changes and the effect sizes in those groups of patients who reported improvement
      and no change in self-report questions (overall, physical, mental and social
      health status) and clinical characteristics (number of opportunistic infections,
      number of symptoms, viral load level and CD4+ count). RESULTS: Ceiling effects
      were found in HRQoL scores at baseline and after 3 months of treatment in Pain
      (42.3-41.6%), Role Function (73.1-77.6%) and Social Function (60.9-63%) on MOS
      HIV subscales, and in Social Support (38.2-37.6%) and Partner Intimacy (38.2
      33.7%) on MQOL-HIV. For patients who improved in self-reported and objective
      clinical indicators of health status, mean percentage of dimensions with
      statistically significant pre-post-treatment changes was 86.4% on MOS-HIV and 50%
      on MQOL-HIV, where mean standardized effect size was 0.45 on MOS-HIV and 0.33 on
      MQOL-HIV for the total of dimensions. CONCLUSIONS: Based on sensitivity to change
      the results suggest that for 3 months both questionnaires can be used, but the
      MOS-HIV is more sensitive than the MQOL-HIV for use in clinical research.

PMID- 10930161
TI  - Quality of life assessment comes of age in the era of highly active
      antiretroviral therapy.

PMID- 10930162
TI  - Salvage therapy with abacavir plus efavirenz or nevirapine in HIV-1-infected
      persons with previous nucleoside analogue and protease inhibitor use.

PMID- 10930163
TI  - Increased beta-chemokine production in peripheral blood mononuclear cells derived
      from HIV-1-infected individuals by a cationic amphiphilic drug (AY 9944) in
      vitro.

PMID- 10930164
TI  - Absence of an association between the presence of human herpesvirus 8 antibodies
      and the development of Kaposi's sarcoma in HIV-1-infected patients receiving
      antiretroviral therapy.

PMID- 10930165
TI  - Stanford V regimen and concomitant highly active antiretroviral therapy is
      feasible and active in patients with Hodgkin's disease and HIV infection.

PMID- 10930166
TI  - Antiretroviral resistance testing policy in England's north Thames HIV units: a
      survey of current practice.

PMID- 10930167
TI  - Increased serum levels of CD44s and CD44v6 in patients with AIDS-related non
      Hodgkin's lymphoma.

PMID- 10930168
TI  - Changes in HIV/AIDS prevention indicators in the rural district of Lira in
      Uganda.

PMID- 10930169
TI  - Beta3-adrenergic receptor polymorphism and the antiretroviral therapy-related
      lipodystrophy syndrome.

PMID- 10930170
TI  - TT virus DNA in serum, peripheral blood mononuclear cells and semen of patients
      infected by HIV.

PMID- 10930171
TI  - Nelfinavir pharmacokinetics in HIV-infected children: a comparison of twice daily
      and three times daily dosing.

PMID- 10930172
TI  - HIV-1 testing in pregnancy: acceptability and correlates of return for test
      results.

PMID- 10930173
TI  - Efficacy and safety of the combination of efavirenz and abacavir in HIV-infected
      patients failing antiretroviral therapy.

PMID- 10930174
TI  - Primary infection with human herpesvirus 8 in an HIV-1-infected patient.

PMID- 10930175
TI  - HIV-1 resistance genotyping by sequencing produces inconsistent results for mixed
      viral populations.

PMID- 10930176
TI  - A case-control study of virological and immunological effects of highly active
      antiretroviral therapy in HIV-infected patients with advanced age.

PMID- 10930177
TI  - The future of genetic association studies in hypertension: improving the signal
      to-noise ratio.

PMID- 10930178
TI  - The role of size at birth and postnatal catch-up growth in determining systolic
      blood pressure: a systematic review of the literature.
AB  - OBJECTIVE: To conduct a systematic review in order to (i) summarize the
      relationship between birthweight and blood pressure, following numerous
      publications in the last 3 years, (ii) assess whether other measures of size at
      birth are related to blood pressure, and (iii) study the role of postnatal catch
      up growth in predicting blood pressure. DATA IDENTIFICATION: All papers published
      between March 1996 and March 2000 that examined the relationship between birth
      weight and systolic blood pressure were identified and combined with the papers
      examined in a previous review. SUBJECTS: More than 444,000 male and female
      subjects aged 0-84 years of all ages and races. RESULTS: Eighty studies described
      the relationship of blood pressure with birth weight The majority of the studies
      in children, adolescents and adults reported that blood pressure fell with
      increasing birth weight, the size of the effect being approximately 2 mmHg/kg.
      Head circumference was the only other birth measurement to be most consistently
      associated with blood pressure, the magnitude of the association being a decrease
      in blood pressure by approximately 0.5 mmHg/cm. Skeletal and non-skeletal
      postnatal catch-up growth were positively associated with blood pressure, with
      the highest blood pressures occurring in individuals of low birth weight but high
      rates of growth subsequently. CONCLUSIONS: Both birth weight and head
      circumference at birth are inversely related to systolic blood pressure. The
      relationship is present in adolescence but attenuated compared to both the pre-
      and post-adolescence periods. Accelerated postnatal growth is also associated
      with raised blood pressure.

PMID- 10930179
TI  - Association between blood pressure, the treatment of hypertension, and
      cardiovascular risk factors in women.
AB  - OBJECTIVE: To examine relationships of normal blood pressure (BP), hypertension
      and degree of BP control with cardiovascular disease (CVD) risk factors and
      predicted 10-year risks for coronary heart disease (CHD) and stroke. DESIGN:
      Cross-sectional survey. SETTING: 107 Marks and Spencer retail stores in the UK.
      PARTICIPANTS: 14,077 women, aged 30-64 years, screened for CVD risk factors
      between 1988 and 1991. MAIN OUTCOME MEASURES: Systolic (SBP) and diastolic (DBP)
      BP; total, high-(HDL) and low-density lipoprotein (LDL) cholesterol, ratio of
      total to HDL cholesterol (TC/HDL-C); triglycerides, apolipoprotein A1,
      apolipoprotein B, lipoprotein (a), glucose, body mass index, antihypertensive
      medication and predicted risks for CHD and stroke. Hypertension was defined as
      SBP > or = 140 mmHg and/or DBP > or = 90 mmHg and/or taking anti-hypertensive
      medication. Subjects were divided into normotensives with optimal (n = 6,599),
      normal (n = 3,170) and high normal (n = 2,184) BP levels, and hypertensives with
      adequate BP control (n = 228), untreated (n = 1,729) and inadequate BP control (n
      = 291). RESULTS: BP level was associated with other CVD risk factors among both
      normotensives and hypertensives. Women with inadequately controlled BP had the
      worst risk profile, followed by untreated hypertensives, those with adequately
      controlled BP and normotensives. Odds ratios for being in the top quintile of
      predicted 10-year CHD and stroke risks were 1, 2.7, 4.2, 8.5, 13.0, 18.9 for CHD;
      1, 1.1, 5.8, 18.7, 20.6, 756 for stroke, for optimal, normal, high normal,
      adequate BP control, untreated and inadequate BP control groups respectively.
      CONCLUSIONS: Untreated hypertensives and women taking anti-hypertensive
      medication but with BP > or = 140/90 mmHg have the most atherogenic risk factor
      profiles. Effective management of BP and the associated CVD risk requires a multi
      factorial approach, rather than addressing BP control in isolation.

PMID- 10930180
TI  - Growth in utero and blood pressure levels in the next generation.
AB  - OBJECTIVE: To determine whether blood pressure levels in adult life are related
      to the mother's fetal growth and size at birth. DESIGN: A follow-up study of men
      and women whose mothers' or fathers' size at birth was recorded in Preston,
      Lancashire, UK. SUBJECTS: Two hundred and twenty-eight men and women born in
      Preston, Lancashire, UK, and still living in Lancashire. MAIN OUTCOME MEASURES:
      Blood pressure at 18-40 years of age. RESULTS: Systolic and diastolic pressures
      fell with increasing mother's birthweight and head circumference. Systolic
      pressure fell by 2.4 mmHg (95% confidence interval (CI) 0.1-4.7) for each pound
      increase in mother's birthweight and by 4.0 mmHg (95% CI 0.2-7.8) for each one
      inch increase in head circumference. These associations were little changed by
      adjusting for length of gestation or for the subject's age, sex, body mass index
      or alcohol consumption. They were independent of the mother's blood pressure. As
      expected, mothers' birthweights were strongly related to their children's
      birthweights (P= 0.009), but the association between mother's birthweight and
      offspring's blood pressure was largely independent of this. Father's size at
      birth was not related to the offspring's blood pressure. CONCLUSIONS: If the
      growth of a female fetus is constrained by lack of nutrients, there are
      persisting changes in her physiology and metabolism which lead to reduced fetal
      growth and raised blood pressure in the next generation. Public health policies
      to improve fetal growth in one generation may therefore benefit succeeding
      generations as well.

PMID- 10930181
TI  - Prediction of stroke by ambulatory blood pressure monitoring versus screening
      blood pressure measurements in a general population: the Ohasama study.
AB  - OBJECTIVE: To investigate the association between 24 h, daytime and night-time
      ambulatory blood pressures and first symptomatic stroke, to compare their
      predictive powers for stroke with that of casual (screening) blood pressure, and
      to compare the predictive power for stroke between daytime and night-time blood
      pressures, in a general population in Ohasama, Japan. DESIGN: A prospective
      cohort study. SUBJECTS AND METHODS: We obtained ambulatory blood pressure on
      1,464 subjects aged > or = 40 years without history of symptomatic stroke, then
      followed-up their stroke-free survival. There were 74 first symptomatic stroke
      during the follow-up period (mean = 6.4 years). The prognostic significance of
      blood pressure for stroke risk was examined by a Cox proportional hazards
      regression model adjusted for possible confounding factors. RESULTS: The non
      parametric and parametric analysis indicated that 24-h, daytime and night-time
      ambulatory blood pressures were linearly related with stroke risk. The likelihood
      ratio analysis demonstrated that these ambulatory blood pressures were
      significantly better related to stroke risk than did screening blood pressure,
      and that daytime blood pressure better predicted stroke risk than did night-time
      blood pressure. CONCLUSIONS: The present study which prospectively investigated
      the relation between ambulatory blood pressure and first symptomatic stroke risk
      in a general population demonstrated that (i) ambulatory blood pressure values
      were linearly related to stroke risk; (ii) ambulatory blood pressures had the
      stronger predictive power for stroke risk than did screening blood pressure; and
      (iii) daytime blood pressure better related to stroke risk than did night-time
      blood pressure.

PMID- 10930182
TI  - G-protein beta3 subunit 825T allele and response to dietary salt in normotensive
      men.
AB  - BACKGROUND AND AIMS: A functional single-nucleotide variant of the gene encoding
      the beta3 subunit of heterotrimeric G proteins (Gbeta3 C825T), associated with
      enhanced G-protein activation and increased activity of the sodium-proton
      exchanger (NHE1), has been implicated in the development of hypertension. Given
      the possible involvement of NHE1 in sodium homeostasis, we tested the hypothesis
      that the Gbeta3 825T allele determines the response of the renin-angiotensin
      system and blood pressure to dietary salt restriction. METHODS: Young
      normotensive men (20-30 years old, n = 193) were recruited within the framework
      of the Berlin Salt-Sensitivity Trial and studied on low- (20 mmol/day) and high
      salt (220 mmol/day) dietary protocols. Subjects were characterized for parameters
      of the renin-angiotensin system and blood pressure response and genotyped for the
      Gbeta3 C825T polymorphism. RESULTS: The genotype distribution was in Hardy
      Weinberg equilibrium (CC = 90, CT = 81 and TT = 22). The responses of the renin
      angiotensin system and blood pressure to the dietary protocol were virtually
      identical between the genotypic groups. Furthermore, when subjects were
      classified as salt-resistant (n = 145) or salt-sensitive (n = 48), genotype
      distribution was comparable between the two groups (salt-resistant: TT = 17, CT =
      60, CC = 68, qT = 0.32; salt-sensitive: TT = 5, CT = 21, CC = 22, qT = 0.32).
      CONCLUSION: These findings do not support the hypothesis that the Gbeta3 C825T
      polymorphism determines the response of the renin-angiotensin system to salt
      depletion or can serve as an early genetic marker of salt sensitivity in young
      normotensive men.

PMID- 10930183
TI  - Japanese individuals do not harbor the T594M mutation but do have the P592S
      mutation in the C-terminus of the beta-subunit of the epithelial sodium channel:
      the Ohasama study.
AB  - OBJECTIVE: To assess the implications of polymorphisms of the amiloride-sensitive
      epithelial sodium channel in essential hypertension in the Japanese population by
      determining the incidence of the T594M mutation in the , subunit of the
      epithelial sodium channel, and by screening the C-terminus of the epithelial
      sodium channel. METHODS: Single-strand confirmational polymorphism (SSCP)
      analysis using two sets of primers which cover the last two-thirds of the last
      exon coding the B epithelial sodium channel and modification of a specific enzyme
      restriction site (NlaIII) for the T594M mutation were performed on 803 Japanese
      subjects. They were randomly selected from the study participants representative
      of a general population of Ohasama, Japan, who measured their home blood
      pressure. Polymerase chain reaction (PCR) products presenting a shift in SSCP
      gel, as well as controls, were directly sequenced by autoanalyser to identify the
      mutation. RESULTS: SSCP analysis identified altered migration in five subjects.
      Four SSCP variants found by sequencing were heterogeneous for the P592S (CCT to
      TCT) mutation conserving the PY motif, although it was not significantly
      associated with either home or casual blood pressure values. The resting
      polymorphism was at codon Thr 594, leading to no change in the amino acid
      sequence (ACG to ACA). None of the PCR products were modified by NlaIII,
      indicating the absence of the T594M mutation. CONCLUSIONS: The epithelial sodium
      channel variants at the C-terminus are not involved in the common form of
      essential hypertension in Japanese.

PMID- 10930185
TI  - Nitric oxide synthase induction by ouabain in vascular smooth muscle cells from
      normotensive and hypertensive rats.
AB  - OBJECTIVE: To investigate the effect of ouabain on inducible nitric oxide
      synthase (iNOS) activity and expression in cytokine-stimulated vascular smooth
      muscle cells (VSMC) from normotensive Wistar-Kyoto (WKY) rats and spontaneously
      hypertensive rats (SHR). METHODS: VSMC were treated for 24 h and afterwards,
      nitric oxide (NO) release was determined by the production of nitrite, a stable
      metabolite of NO. Activity of iNOS was measured by the conversion of [3H]-L
      arginine to [3H]-L-citrulline and iNOS protein expression by Western blotting.
      RESULTS: Ouabain (0.01-1 mmol/l) further enhanced interleukin-1beta (II-1beta)
      induced nitrite production by WKY and SHR VSMC, although a more pronounced effect
      was observed in SHR cells (maximum response 52.1 +/- 5.2 and 71.2 +/- 6.4% of 11
      1beta effect in WKY and SHR cells, respectively). Such response on NO release was
      mimicked by the calcium ionophore A 23187 (0.01-1 micromol/l) and abolished by
      the voltage-operated calcium channels (VOCC) nifedipine (0.1 micromol/l).
      Expression of iNOS showed that ouabain increased the synthesis of the enzyme in
      WKY and SHR VSMC stimulated with II-1beta, and this effect was higher in SHR
      cells. The increased iNOS expression was significantly reduced by nifedipine.
      CONCLUSIONS: Ouabain stimulation of iNOS expression and activity in II-1beta
      stimulated VSMCs from WKY rats and SHR seems to be related to increased
      intracellular calcium influx through VOCC. The more pronounced effect observed in
      SHR VSMC could be explained by an altered calcium entry in the hypertensive
      strain.

PMID- 10930184
TI  - Lack of association of the angiotensinogen-6 polymorphism with blood pressure
      levels in the comprehensive NHLBI Family Blood Pressure Program. National Heart,
      Lung and Blood Institute.
AB  - OBJECTIVE: To evaluate the association between the angiotensinogen-6 polymorphism
      (AGT-6) and blood pressure levels. DESIGN: Data were analysed from the first
      4,322 subjects of the NHLBI Family Blood Pressure Program (FBPP), consisting of
      four networks (GenNet, GENOA, HyperGEN and SAPPHIRe), each conducting a
      multicentre observational family study to identify and characterize the genetic
      determinants of hypertension and blood pressure. The four studies use different
      designs (concordant sibpairs, discordant pairs, sibships, extended pedigrees),
      target different ethnic groups (Caucasian, African-American, Japanese, Chinese),
      and have different inclusion/exclusion criteria. However, the protocols and
      definitions were standardized across networks before data collection to allow
      maximum poolability. METHODS: Each network/racial group was analysed separately,
      using generalized linear models that accounted for the non-independence of family
      members and/or the confounding of anti-hypertensive medications as needed. The
      results were also pooled using a pre-planned meta-analysis technique. RESULTS:
      AGT-6 was not significantly associated with blood pressure in any network/racial
      group. In the meta-analysis, the pooled effect of AGT-6 was small [hazard ratio =
      1.10, 95% confidence interval (CI) = 0.99-1.22, P= 0.0647 for systolic; hazard
      ratio = 1.04, 95% CI = 0.89-1.21, P= 0.6383 for diastolic]. A post-hoc analysis
      restricting to subjects meeting JNC VI criteria for Stage I hypertension (blood
      pressure > 140/90 mmHg or medicated) showed a stronger statistically significant
      relationship for systolic blood pressure (hazard ratio = 1.44, 95% CI = 1.04
      2.00, P= 0.0283). CONCLUSIONS: AGT-6 has minimal to no effect on the inter
      individual variation of blood pressure levels, and is at best a 'minor gene' for
      blood pressure in the population as a whole.

PMID- 10930186
TI  - Time course of apoptosis in small resistance arteries of spontaneously
      hypertensive rats.
AB  - OBJECTIVE: The time course of programmed cell death (apoptosis) in the
      vasculature of spontaneously hypertensive rats (SHRs) is still unclear. Moreover,
      no data are presently available about the possible inter-relationships between
      apoptosis and vascular remodelling. The aim of this study was to investigate the
      mesenteric small resistance arteries and large arteries (aortas) of SHRs and
      normotensive Wistar-Kyoto (WKY) rats at different ages, before and after the
      development of overt hypertension. METHODS: Twenty-four SHRs (4, 8 or 12 weeks
      old) and 24 age-matched WKY rats were included in the study. Blood pressure was
      measured non-invasively. Rats were killed by decapitation and segments of aortas
      and small mesenteric arteries were dissected free from the surrounding tissue.
      Mesenteric arteries were mounted on a micromyograph and structural
      characteristics were measured (media thickness, media:lumen ratio, etc.).
      Apoptotic cells in the tunica media of large and small vessels were then stained
      using modified TdT-mediated dUTP Nick-End Labeling (TUNEL). RESULTS: At 4 weeks
      of age no difference in the blood pressure and percentage of apoptosis in
      mesenteric arteries between SHRs and WKY rats was detected; however, the
      media:lumen ratio of mesenteric small resistance arteries was significantly
      greater in SHRs. At 8 and 12 weeks of age systolic blood pressure, media:lumen
      ratio and apoptosis rate in mesenteric small arteries was significantly higher in
      SHRs. The rate of apoptosis in the aortas was similar in the two strains at all
      three ages. CONCLUSIONS: An increased prevalence of apoptosis was observed in
      mesenteric small arteries of 8- and 12-week-old SHRs. It is possible that
      apoptosis may exert a role in small resistance artery remodelling during the
      development and establishment of hypertension.

PMID- 10930187
TI  - Endothelin-1-receptor-mediated responses in resistance vessels of young and adult
      spontaneously hypertensive rats.
AB  - OBJECTIVE: To assess whether primary changes in endothelin-1 (ET-1) receptor
      responsiveness or secondary vessel functional modifications could characterize
      the effects evoked by ET-1 in the mesenteric vascular bed (MVB) of
      prehypertensive 5-week-old and 12-week-old spontaneously hypertensive rats
      (SHRs). DESIGN AND METHODS: We used male 5-week-old and 12-week-old SHRs and sex-
      and age-matched Wistar-Kyoto (WKY) rats as controls. ET-1 receptor responsiveness
      was evaluated by ET-1 (0.04-2 micromol/l) concentration-response curves and
      repeated with indomethacin and BQ-123 (0.1-0.5 micromol/l), the latter a
      selective ETA receptor antagonist. ETB receptor responsiveness was tested by
      sarafotoxin S6c (1-100 nmol/l) and IRL-1620 (0.1-10 nmol/l) concentration
      response curves, obtained in the noradrenaline-precontracted MVB. RESULTS: At 5
      weeks of age, ET-1 induced a similar concentration-dependent contraction in SHRs
      and WKY rats, with an overlapping BQ-123 pA2 value (negative common logarithm of
      the antagonist that produces an agonist dose ratio of 2) in the two strains.
      Indomethacin was ineffective in both groups. Sarafotoxin S6c and IRL-1620 both
      evoked an ETB-mediated, significant relaxation, only in WKY rats. In 12-week-old
      SHRs, ET-1 evoked a markedly increased maximal effect compared with the response
      in WKY rats (P< 0.01); this was prevented by treatment with indomethacin. The BQ
      123 pA2 value was higher in SHRs than in WKY rats (P< 0.01). Both sarafotoxin S6c
      and IRL-1620 evoked a significant concentration-dependent relaxation in WKY rats,
      which was not detected in SHR preparations. CONCLUSIONS: Our results could
      suggest that the different responses evoked by ET-1 in the MVB of SHRs during the
      onset of hypertension may be related partially to primary alterations in the ET-1
      receptorial pattern and partially to the onset of high blood pressure, leading to
      an impairment in the haemodynamic balance.

PMID- 10930188
TI  - Does hypertension confer a hypercoagulable state in stroke-prone spontaneously
      hypertensive rats?
AB  - OBJECTIVE: To verify whether hypertension confers a hypercoagulable state in a
      hypertensive animal model. DESIGN: The parameters of blood coagulation were
      compared between stroke-prone spontaneously hypertensive rats (SHR-SP) and Wistar
      Kyoto (WKY) rats. Each rat group consisted of a younger subgroup at 8-12 weeks
      old (n = 12) and an older subgroup at 16-20 weeks old (n = 12). METHODS:
      Prothrombin time (PT), activated partial thromboplastin time (APTT), fluorogenic
      PT, fibrinogen, fibrin/fibrinogen degradation products (FDP), thrombin-anti
      thrombin III complex (TAT), factor Xa activity, anti-thrombin III (AT-III),
      tissue factor pathway inhibitor (TFPI), protein C and C1 inhibitor were measured
      in both rat groups. RESULTS: There was no significant difference in FDP and TAT
      levels between SHR-SP and WKY rats even at 16-20 weeks when SHR-SP developed
      severe hypertensive vascular lesions. Contrary to expectations, fluorogenic PT
      and factor Xa activity were significantly lower in SHR-SP than in WKY rats. While
      there was no significant difference in AT-III, TFPI and protein C activities
      between SHR-SP and WKY rats, C1 inhibitor activity was significantly higher in
      SHR-SP than in WKY rats. The elevated C1 inhibitor activity was inversely
      correlated with the reduced factor Xa activity. Gel-filtered fractionated plasma
      with C1 inhibitor activity had an inhibitory effect on the purified rat factor
      Xa, and immunodepletion of C1 inhibitor from the fractionated plasma attenuated
      the inhibitory effect CONCLUSION: These results suggest that SHR-SP get into a
      hypocoagulable state rather than a hypercoagulable state, and that the reduction
      of factor Xa activity in SHR-SP may be related to the elevation of C1 inhibitor
      activity.

PMID- 10930189
TI  - Oestrogen attenuates the increases in blood pressure and platelet aggregation in
      ovariectomized and salt-loaded Dahl salt-sensitive rats.
AB  - OBJECTIVE: To investigate the effects of oestrogen supplementation after
      ovariectomy on systolic blood pressure and platelet aggregation on different
      sodium content diet in the female Dahl salt-sensitive rats. METHODS: At 12 weeks
      of age, rats were ovariectomized or sham-operated and were fed either a high NaCl
      (8%) or low NaCl (0.3%) diet Ovariectomized rats were treated with either 17beta
      oestradiol or placebo for 8 weeks, whereas sham-operated rats received placebo
      alone. After 8 weeks, the systolic blood pressure and platelet aggregation were
      measured and analysed by two-way analysis of variance. RESULTS: The systolic
      blood pressure of ovariectomized rats was significantly higher than that of sham
      operated rats, and this increase in systolic blood pressure was suppressed by
      oestrogen supplementation. Systolic blood pressure was inversely correlated with
      plasma 17beta-oestradiol levels (r= -0.77, P< 0.01) and with the uterus weight to
      body weight ratio (r = -0.47, P < 0.01). Platelet aggregation was significantly
      enhanced by salt loading. Salt loading and female hormonal manipulation
      significantly interacted on platelet aggregation. Only in Dahl salt-sensitive
      rats fed a low sodium diet, ovariectomy increased platelet aggregation, whereas
      hormone replacement did not improve it. In Dahl salt-sensitive rats fed a high
      sodium diet, hormone replacement reduced platelet aggregation. CONCLUSIONS:
      Oestrogen replacement suppresses the development of hypertension and attenuates
      platelet aggregatory function in the salt-loaded ovariectomized Dahl salt
      sensitive rats. It has a potential to inhibit the atherosclerotic process in
      postmenopausal hypertension.

PMID- 10930190
TI  - Effect of oral magnesium supplementation on blood pressure, platelet aggregation
      and calcium handling in deoxycorticosterone acetate induced hypertension in rats.
AB  - OBJECTIVE: To study the effect of oral magnesium supplementation on blood
      pressure, platelet aggregation and platelet calcium handling in
      deoxycorticosterone acetate (DOCA)-induced hypertension in rats. DESIGN AND
      METHODS: Rats were divided into four groups of 20 each. Drug treatments were
      given for a 6-week period. Control rats were vehicle treated. In the second
      group, DOCA, 15 mg/kg, was injected subcutaneously twice weekly with 1% NaCl used
      instead of drinking water. The third group was given magnesium oxide (MgO), 1
      g/kg daily, orally by gavage. The fourth group was given MgO along with DOCA and
      1% NaCl. Blood pressure and heart rate were measured weekly. Platelet
      aggregation, intracellular calcium, calcium uptake and calcium efflux studies
      were performed at the end of sixth week. Serum magnesium concentration, plasma
      levels of reactive nitrogen intermediates (RNI) and citrulline were also measured
      RESULTS: There was a significant rise in blood pressure in the DOCA-treated rats.
      Magnesium prevented the gradual rise in blood pressure when given along with
      DOCA, but had no effect in normotensive rats. Heart rate did not show any
      significant change. Platelet aggregation was significantly reduced in all the
      treatment groups compared to the control group. DOCA treatment produced a
      significant increase in the intracellular calcium concentration as well as the
      calcium uptake compared to the control group. Magnesium supplementation inhibited
      the increased intracellular calcium concentration and calcium uptake in DOCA
      treated rats. RNI and citrulline levels were elevated in all the treatment
      groups. Serum magnesium levels were significantly higher in the magnesium-treated
      and DOCA plus magnesium-treated rats. CONCLUSIONS: Magnesium supplementation
      prevents blood pressure elevation in DOCA hypertensive rats. These effects are
      associated with inhibition of platelet calcium uptake and decreased intracellular
      free calcium concentration.

PMID- 10930191
TI  - Effects of chronic neutral endopeptidase inhibition in rats with cyclosporine
      induced hypertension.
AB  - OBJECTIVE: Cyclosporine (CysA), a potent immunosuppressant, is associated with
      hypertension and nephrotoxicity. Neutral endopeptidase (NEP) degrades vasoactive
      peptides, including the natriuretic peptides and endothelin-1 (ET-1). We
      conducted the present study to determine whether or not the NEP inhibitor,
      ecadotril, prevents cyclosporine-induced hypertension and to clarify the
      mechanisms responsible for the hypotensive effects of ecadotril. DESIGN AND
      METHODS: We studied the chronic effects of ecadotril (30 mg/kg per day) on blood
      pressure; the production of ET-1 and C-type natriuretic peptide (CNP);
      endothelial nitric oxide synthase (eNOS) activity; and the expression of
      messenger RNA (mRNA), for each substance in blood vessels of CysA-induced
      hypertensive rats. RESULTS: CysA (25 mg/kg per day) given for 4 weeks increased
      the blood pressure from 116 +/- 14 mmHg to 159 +/- 15 mmHg, in rats. This
      increase was blunted by the co-administration of ecadotril (blood pressure: 134
      +/- 14 mmHg). CysA increased plasma NEP activity. CysA increased the production
      of ET-1 and the expression of ET-1 mRNA without affecting CNP synthesis and
      endothelin converting enzyme (ECE)-1 mRNA expression. CysA decreased the eNOS
      activity and eNOS mRNA levels. Addition of the NEP inhibitor decreased the
      synthesis of ET-1 and ET-1 mRNA levels and increased the eNOS activity and the
      eNOS mRNA levels. Vascular CNP synthesis and ECE-1 mRNA expression in rats
      treated with ecadotril did not differ from those in rats treated with CysA and
      ecadotril. CONCLUSION: These results indicate that chronic NEP inhibition may
      prevent the CysA-induced hypertension by decreasing local ET-1 synthesis and
      partly increasing vascular nitric oxide production.

PMID- 10930192
TI  - The expression of renin-binding protein and renin in the kidneys of rats with two
      kidney one-clip hypertension.
AB  - OBJECTIVE: To test the hypothesis that renin-binding protein (RnBP) is involved
      in modulating the intracellular processing or release of renin, we examined the
      expression of RnBP in clipped and contralateral kidneys of rats with two-kidney
      one-clip hypertension, and in left and right kidneys from sham-operated control
      rats. DESIGN AND METHODS: Kidneys from rats with two-kidney one-clip hypertension
      and from control rats were either snap-frozen for extraction of mRNA or fixed for
      in-situ hybridization and immunochemistry. Reverse-transcription polymerase chain
      reaction on renal mRNA was performed using primers for renin, RnBP,
      glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and angiotensin-converting
      enzyme (ACE). In addition, renal total RNA was analysed by Northern blotting for
      RnBP, GAPDH and angiotensin II type 1A (AT1A) receptor mRNA, and the intensity of
      the bands was measured by laser densitometry. In situ hybridization for renin
      mRNA was carried out using digoxygenin-labelled antisense oligonucleotides and
      for RnBP using labelled antisense oligonucleotides and an antisense riboprobe.
      Controls included sections treated with RNase and sections stained with sense
      oligonucleotides. RESULTS: The level of expression of mRNA for RnBP is similar in
      clipped and contralateral kidneys of renal hypertensive rats; in contrast, renin
      mRNA expression is upregulated in the clipped kidney. Renin-binding protein is
      expressed mainly in renal tubules and collecting ducts unlike renin, which is
      expressed in the glomerular afferent arteriole. We did not detect lateralization
      of expression for ACE or the AT1A receptor between clipped and contralateral
      kidneys. CONCLUSION: Renin-binding protein expression is unchanged between
      clipped and contralateral kidneys. Therefore, a physiological stimulus that
      upregulates renin gene expression in clipped kidneys does not affect RnBP
      expression. The main sites of RnBP expression are the renal tubules and
      collecting ducts; in contast renin is expressed at the glomerular pole. The
      results show that RnBP is not colocalized or coregulated with renin in this model
      of hypertension.

PMID- 10930194
TI  - Long-term blood pressure telemetry in AT2 receptor-disrupted mice.
AB  - OBJECTIVES: The hypertension in AT2 receptor knockout mice is imperfectly
      defined. Therefore, we investigated the influence of dietary salt loading and
      deoxycorticosterone (DOCA)-salt treatment on blood pressure and diurnal patterns
      of blood pressure in these mice by radiotelemetry. METHODS: We used telemetry in
      AT2 receptor knockout and wild-type mice to measure blood pressure, heart rate,
      aortic pressure dp/dt, locomotor activity, and circadian rhythms. Salt-related
      effects were studied by increasing the salt in chow to 4%, adding 1% saline in
      drinking water, and by DOCA-salt treatment RESULTS: Baseline blood pressures were
      higher in AT2 receptor knockout than in wild-type mice and were not affected by
      increasing the salt intake. The blood pressure increase was steeper and greater
      in AT2 receptor knockout than in wild-type mice after DOCA-salt treatment A
      circadian rhythm of blood pressure and heart rate, with higher values during the
      night, was seen in wild-type, but not in AT2 receptor knockout mice. In AT2
      receptor knockout mice, this rhythm was only significant when daily salt intake
      was increased or when DOCA-salt hypertension was induced. The acrophase of blood
      pressure and heart rate was found between 2000 and 2400 h and was in accordance
      with the maximum physical activity. CONCLUSION: These data suggest that AT2
      knockout mice display slight hypertension which is not salt-sensitive. On the
      other hand, the susceptibility to develop DOCA-salt hypertension is increased.
      The study also illustrates the power of telemetry in monitoring long-term
      cardiovascular changes and circadian blood pressure and heart rate rhythms in
      genetically engineered mice.

PMID- 10930193
TI  - Autoantibodies against the angiotensin receptor (AT1) in patients with
      hypertension.
AB  - Sera from patients with malignant essential hypertension (n = 14), malignant
      secondary hypertension mainly attributable to renovascular diseases (n = 12) and
      renovascular diseases without malignant hypertension (n = 11) and from
      normotensive healthy blood donors (n = 35) were studied for the presence of
      autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies
      against the angiotensin II receptor (AT1) were detected in 14, 33, 18 and 14% of
      patients with malignant essential hypertension, malignant secondary hypertension,
      renovascular diseases and control patients, respectively. Sensitivity of the
      enzyme immunoassay was assessed as 5 microg/ml IgG. Patients did not show
      antibodies against bradykinin (B2) or angiotensin II subtype 2 (AT2) receptors.
      Autoantibodies affinity-purified from positive patients localized AT receptors in
      Chinese hamster ovary transfected cells, and displayed a positive chronotropic
      effect on cultured neonatal rat cardiomyocytes. These results demonstrate the
      existence of autoantibodies against a functional extracellular domain of human
      AT1 receptors in patients with malignant hypertension, and suggest that these
      autoantibodies might be involved in the pathogenesis of malignant hypertension.

PMID- 10930196
TI  - The role of the 11beta-hydroxysteroid dehydrogenase type 2 in human hypertension.

PMID- 10930195
TI  - Renal haemodynamics and sodium excretory capacity during urapidil treatment in
      patients with essential hypertension.
AB  - OBJECTIVE: Since renal sympathetic nerves are involved in the regulation of
      sodium excretion, we investigated whether treatment with urapidil, an alpha1
      adrenoceptor blocking agent which also lowers sympathetic activity, alters sodium
      excretory capacity in patients with essential hypertension. DESIGN: A double
      blind, randomized, parallel-group study. METHODS: Studies were carried out in 26
      patients who were randomized to treatment with either placebo or urapidil for 8
      weeks. Before and after treatment blood pressure, renal haemodynamics and various
      neurohormones were measured, as well as the response of these variables to a
      hypertonic saline infusion. RESULTS: Urapidil had no effect on renal
      haemodynamics or neurohormones at rest However, as compared to placebo the saline
      induced rises in renal plasma flow and glomerular filtration rate lasted longer
      during treatment with urapidil. Responses of renin, angiotensin II and
      catecholamines were not modified by urapidil. On the other hand, aldosterone was
      less suppressed while atrial natriuretic peptide was less stimulated following
      the saline load when patients had been treated with urapidil. Cumulative sodium
      excretion during a 3 h period from the moment of saline infusion was similar
      whether patients had been treated with placebo or with urapidil. CONCLUSIONS: Our
      data show that urapidil interferes with renal haemodynamics after sodium loading
      but that any tendency to promote sodium output may be offset by changes in
      aldosterone and atrial natriuretic peptide. We conclude that urapidil, under the
      circumstances tested, does not affect the sodium excretory capacity of the
      kidney.

PMID- 10930197
TI  - Reflections on hypotension during Cesarean section under spinal anesthesia: do we
      need to use colloid?

PMID- 10930198
TI  - Anesthesia assistants in Canada.

PMID- 10930199
TI  - Hydroxyethylstarch 10% is superior to Ringer's solution for preloading before
      spinal anesthesia for Cesarean section.
AB  - PURPOSE: To compare the preloading effect of 500 ml hydroxyethylstarch (HES) 10%
      with 1 L Lactated Ringer's solution (LR). METHODS: In 40 healthy women undergoing
      elective Cesarean section HES, 500 ml (n = 20), or LR, IL (n = 20), was
      administered during 10 min before spinal anesthesia. The incidence of
      hypotension, (systolic blood pressure < 80% of baseline and < 100 mm Hg), and the
      amount of ephedrine used to treat it were compared. Also, the incidence of nausea
      and/or vomiting were recorded. Neonatal outcome was assessed using Apgar scores
      and umbilical venous and arterial blood gases. RESULTS: The incidence of
      hypotension was higher in the LR than in HES group (80% vs 40%). Mean minimum
      systolic blood pressure was lower in the LR than in the HES group (86.1 +/- 12.7
      mm Hg vs 99.6 +/- 9.7 mm Hg P < 0.05). Systolic blood pressure < 90 mmHg occurred
      in two of 20 patients (10%) who received HES vs 11 of 20 patients (55%) who
      received LR (P < 0.05). More doses of ephedrine were required to treat
      hypotension in the LRthan in the HES group (35.3 +/- 18.4 mg vs 10.6 +/- 8.6 mg;
      P < 0.05). The incidence of nausea and/or vomiting was lower in the HES than in
      the crystalloid group. Neonatal outcome was good and similar in both groups.
      CONCLUSION: Preloading patients undergoing elective Cesarean section with 500 ml
      HES 10%, decreases the incidence and severity of spinal-induced hypotension more
      than preloading with 1 L of LR solution.

PMID- 10930200
TI  - Gastric distension and ventilation during laparoscopic cholecystectomy: LMA
      Classic vs. tracheal intubation.
AB  - PURPOSE: The standard laryngeal mask airway LMA-Classic was designed as an
      alternative to the endotracheal tube (ETT) or the face mask for use with either
      spontaneous or positive pressure ventilation. Positive pressure ventilation may
      exploit leaks around the LMA cuff, leading to gastric distension and/or
      inadequate ventilation. We compared gastric distension and ventilation parameters
      with LMA vs ETT during laparoscopic cholecystectomy. METHODS: One hundred and
      one, ASA I-II adults scheduled for elective laparoscopic cholecystectomy were
      randomly assigned to LMA-Classic or ETT. Patients with BMI >30 kg x m(-2), hiatus
      hernia or gastroesophageal reflux were excluded. Following induction of
      anesthesia, an in-and-out orogastric tube was passed to decompress the stomach
      before insertion of the LMA (women size #4, men size #5) or ETT (women 7 mm, men
      8 mm). Anesthesia was maintained with isoflurane in nitrous oxide and oxygen
      (FIO2 0.3-0.5), rocuronium and fentanyl. The surgeon, blinded to the type of
      airway, scored gastric distention 0-10 at insertion of the laparoscope and
      immediately before removal at the end of the surgical procedure. RESULTS:
      Incidence and degree of change in gastric distension were similar in both groups.
      Ventilation parameters during insufflation (mean +/- SD) for LMA and ETT were:
      S(P)O2 98 +/- I vs 98 +/- I, P(ET)CO2 38 +/- 4 vs 36 +/- 4 mm Hg and airway
      pressure 21 +/- 4 vs 23 +/- 3 cm water. CONCLUSION: Positive pressure ventilation
      with a correctly placed LMA-Classic of appropriate size permits adequate
      pulmonary ventilation. Gastric distension occurs with equal frequency with either
      airway device.

PMID- 10930201
TI  - Oral clonidine premedication reduces propofol requirement for laryngeal mask
      airway insertion.
AB  - PURPOSE: To determine the effect of oral clonidine premedication on propofol
      requirement (ED(50)) for the insertion of the laryngeal mask airway (LMA) in
      healthy patients undergoing abdominal hysterectomy. METHODS: After ethics
      committee approval and informed consent, 41 patients were randomly assigned to
      receive 5 microg x kg(-1) clonidine po premedication 90 min before entering the
      operating room (n = 22), or no clonidine (n = 19). To alleviate pain associated
      with iv propofol, 3 ml lidocaine 2%iv were administered. General anesthesia was
      induced, 30 sec later, with propofol at a rate of 100 mg x min(-1) (600 ml x hr(
      1)) iv. The dose of propofol at which insertion of the LMA was attempted was
      predetermined by modification of Dixon's up-and-down method with an initial dose
      of 2.5 mg x kg(-1) and 0.25 mg x kg(-1) as the step size. An LMA was inserted,
      without muscle relaxants or other adjuvants 90 sec after completion of the
      propofol injection, by an anesthesiologist blinded to the treatment of the
      patient. RESULTS: The ED(50) of propofol for LMA insertion in clonidine-treated
      patients (2.0 +/- 0.2 mg x kg(-1), 1.8-2.3 mg x kg(-1) [95% confidence
      interval]), was less than that in patients without clonidine (2.5 +/- 0.1 mg x
      kg(-1), 2.4-2.6 mg x kg(-1), P < 0.01). CONCLUSION: Oral clonidine premedication
      reduces propofol requirement for LMA insertion.

PMID- 10930203
TI  - Detection of iatrogenic cardiac tamponade by transesophageal echocardiography
      during vena cava filter procedure.
AB  - PURPOSE: To present a patient who developed cardiac tamponade during insertion of
      an inferior vena cava (IVC) filter. Intraoperative transesophageal
      echocardiography (TEE) was used as a means to diagnose the cardiac tamponade and
      to facilitate guiding of pericardiocentesis. CLINICAL FEATURES: A 45-yr-old man
      with protein S deficiency complicated by repeated attacks of deep vein thrombosis
      and pulmonary thromboembolism was scheduled for insertion of an IVC filter. He
      had history of chronic renal insufficiency, heart failure, and cerebral
      infarction with mild left hemiparesis. Current medication included diltiazem (30
      mg, I tab tid ), prednisolone (5 mg, 2 tabs qd ), and warfarin (2.5 mg daily).
      Preoperative transthoracic echocardiography demonstrated bilateral pleural
      effusions, moderate mitral regurgitation and tricuspid regurgitation, left atrial
      appendage thrombus and severe generalized hypokinesia of left ventricle. Nuclear
      medicine examination by (99)Tc showed ejection fractions of left ventricle and
      right ventricle as 20% and 22%, respectively. Under the impression of protein S
      deficiency with multiple attacks of thromboembolism and failure of anticoagulant
      therapy, he was arranged for the procedure of vena caval filter insertion.
      Unfortunately, iatrogenic cardiac tamponade occurred during the course of the
      procedure with rapid hemodynamic deterioration. Because of the expedient of
      routine monitoring of cardiac condition with TEE, a prompt diagnosis was made. We
      successfully improved the patient's hemodynamic status after transthoracic echo
      guided pericardiocentesis. CONCLUSION: Intraoperative TEE is recommended to be
      used routinely in patients undergoing vena cava filter procedures. The
      availability of echocardiographic monitoring in the operation room allows the
      confirmation of the diagnosis and facilitation pericardiocentesis.

PMID- 10930202
TI  - Hemodynamics, intramucosal pH and regulators of circulation during perioperative
      epidural analgesia.
AB  - PURPOSE: To evaluate the effects of perioperative epidural analgesia on
      hemodynamics, splanchnic perfusion and regulators of circulation. METHODS: Twenty
      patients undergoing aortic surgery were randomised into two groups: epidural
      analgesia group (EAG): epidural analgesia with bupivacaine (15 ml, 0.125%) was
      started before surgery. Eight and 16 hr postoperatively 10 ml bupivacaine 0.125%
      and 1 mg morphine were given. Control group (COG): patients received no epidural
      catheter. Monitoring included pulmonary artery catheter and gastric tonometer.
      Norepinephrine, epinephrine, renin, ADH, ANP and endothelin were measured: before
      epidural analgesia (T0), before aortic clamping (T1), 20 min after aortic
      clamping (T2), after declamping the first leg (T3), at end of surgery (T4), one
      hour (T5) and 24 hr postoperatively (T6). RESULTS: At T5 mean arterial blood
      pressure decreased in EAG compared with baseline (86 +/- 16 to 75 +/- 8 mmHg) and
      compared with COG (75 +/- 8 vs 84 +/- 11 mmHg). At T2 pulmonary capillary wedge
      pressure and cardiac index increased and at T6 decreased in both groups. Systemic
      vascular resistance decreased at T I and at T3-T5 in EAG compared with COG and at
      T1 and T3-T6 to baseline (1472 +/- 448 to 1027 +/- 184 dyn x sec x cm(-5) x m(
      2)). In EAG and in COG, pHi decreased compared with baseline but without group
      differences. In both groups, epinephrine, norepinephrine, renin, and ADH levels
      increased from baseline. Endothelin and ANP levels showed no changes.
      CONCLUSIONS: Perioperatively administrated epidural bupivacaine has no
      beneficially effects on hemodynamics, pHi or release of regulators of
      circulation.

PMID- 10930204
TI  - Liver transplantation in a Jehovah's Witness with ankylosing spondylitis.
AB  - PURPOSE: Orthotopic liver transplantation is typically associated with large
      volume blood loss. Technological and pharmacological advances permit liver
      transplantation in patients who formerly were not candidates for this surgery
      because of strict limitations on blood product administration. We describe a
      liver transplant in a Jehovah's Witness with ankylosing spondylitis. CLINICAL
      FEATURE: A 49-yr-old Jehovah's Witness with ankylosing spondylitis and end stage
      liver disease secondary to sclerosing cholangitis underwent orthotopic liver
      transplantation. Recombinant human erythropoietin (4,000 IU sc every two days for
      four weeks, then 4,000 IU sc every week) established a normal hemoglobin
      concentration preoperatively (> 140 g x L(-1) compared with 120 g x L(-1)
      baseline). Intraoperatively, strategies for reducing risk of blood product
      transfusion included avoidance of hypothermia (T>35 degrees C), minimal blood
      sampling (four 1 ml samples), normovolemic hemodilution (two units),
      administration of Aprotinin (2 million units bolus dose followed by infusion of
      500,000 u x hr(-1)), and return of blood (1,500 ml) scavenged from the operative
      field. Estimated blood loss was 2,200 mi. The preoperative and postoperative
      hemoglobin concentration was 147 g x L(-1) (hematocrit 0.45) and 123 g x L(-1)
      (hematocrit 0.37), respectively. No blood products were required and he was
      discharged three weeks postoperatively without complication. CONCLUSION:
      Technological and pharmacological advances allow patients to undergo surgery
      traditionally associated with large volume blood loss with reduced risk of blood
      product administration.

PMID- 10930205
TI  - Combined surgery for coronary artery disease and pheochromocytoma.
AB  - PURPOSE: To report a case of severe coronary artery disease complicating
      pheochromocytoma, managed with combined coronary artery bypass grafting (CABG)
      and adrenalectomy. CLINICAL FEATURES: A 55-yr-old woman presented with poorly
      controlled hypertension and investigation revealed an active pheochromocytoma of
      her left adrenal gland. During medical preparation for adrenalectomy, she
      developed an acute myocardial infarct complicated with unstable angina. This
      required urgent CABG, and combined surgery for the triple vessels coronary artery
      disease and the pheochromocytoma was planned. We explain the details of medical
      preparation before surgery and the anesthetic considerations during the surgical
      procedure. Postoperative recovery was normal and no complication occurred. Even
      if the pheochromocytoma was malignant, her urinary catecholamines two months
      after the surgery were normal and remain normal after more than two years of
      follow-up. CONCLUSION: We report a patient who underwent combined CABG and
      adrenalectomy for pheochromocytoma. The CABG was done first, followed by the
      adrenalectomy with invasive monitoring. The procedure was well tolerated with
      cure of the two underlying conditions. So we propose that combined procedure
      should be considered in this clinical setting.

PMID- 10930206
TI  - [Perioperative beta-blockers. Part one: fundamentals].
AB  - PURPOSE: To review the pharmacologic and pathophysiologic information necessary
      to prescribe beta-blockers (BB) in perioperative medicine. DATA SOURCE: Manual
      retrieval and electronic research of the literature using MEDLINE (key-words:
      anesthesia and beta- blocker; surgery and beta-blocker). DATA SYNTHESIS:
      Cardioselective BB inhibit preferentially beta-1 receptors, inducing a decrease
      in heart rate and cardiac inotropism leading to reduction of oxygen myocardial
      consumption. Non-cardioselective BB inhibit also beta-2 receptors, increasing
      bronchial and peripheral vascular resistances and uterine contractions. However,
      some BB are also vasodilators (carvedilol, celiprolol, labetalol).
      Contraindications to BB result logically from their pharmacological effects.
      Treatment with BB increases membrane beta-receptor density; this explains
      sympathetic overactivity observed during weaning of treatment. Since the
      discovery of propranolol in 1964, the use of BB has been controversial in
      anesthesia. Formerly, the adverse effects of partial sympatholysis during
      anesthesia and surgery were feared. However, since 1973, experimental and
      clinical data have suggested a protective hemodynamic effect. CONCLUSION:
      Continued administration of BB up to the time of anesthesia has been encouraged
      except in patients with signs of intolerance such as hypotension or excessive
      bradycardia.

PMID- 10930207
TI  - [Perioperative beta-blockers. Part two: therapeutic indications].
AB  - PURPOSE: To review the pharmacologic and pathophysiologic information necessary
      to prescribe beta-blockers (BB) in perioperative medicine. DATA SOURCE: Manual
      retrieval and electronic research of the literature using MEDLINE (key-words:
      anesthesia and beta- blocker; surgery and beta-blocker). DATA SYNTHESIS: In non
      cardiac surgery, the beneficial effects of BB have been demonstrated in
      hypertensive patients since 1979. In 1996, the beneficial effects of atenolol in
      patients with coronary artery disease (reduction of postoperative myocardial
      ischemia and overall reduction in two-year mortality) were demonstrated. In
      coronary surgery, the interest of preoperative BB treatment has been shown since
      1983. Administration of BB has been shown to be beneficial in acute myocardial
      infarction or chronic cardiac failure (except in NYHA class IV patients).
      CONCLUSION: BB have been shown to exert a beneficial effect on postoperative
      outcomes in patients with cardiovascular disease or risk factors, and their more
      widespread use in perioperative medicine is encouraged.

PMID- 10930208
TI  - Milrinone improves intestinal villus blood flow during endotoxemia.
AB  - PURPOSE: To determine whether the compromised intestinal villus blood flow in a
      rat model of endotoxemia could be improved by continuous infusion of the
      phosphodiesterase (PDE) inhibitor milrinone. METHODS: Twenty-four anesthetized
      and ventilated rats were laparotomized and an ileal portion was exteriorized and
      opened by an antimesenteric incision. The ileal segment was fixed with the
      mucosal surface upward. Microcirculatory parameters were assessed by intravital
      videomicroscopy. The animals were randomly assigned to receive one of three
      treatments: infusion of Escherichia coli lipopolysaccharides without
      phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with
      milrinone pretreatment (= milrinone group), or without infusion of LPS or
      milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and
      microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles
      = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured
      30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal
      villus blood flow was calculated from D(A) and V(E). RESULTS: In the milrinone
      group MAP decreased 60 min after induction of endotoxemia whereas it remained
      stable in the control and the LPS group. In both groups given endotoxin V(E)
      decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS
      group, but increased in the milrinone group after 120 min of endotoxemia. Thus,
      the endotoxin-induced decrease of intestinal villus blood flow was diminished but
      not fully restored by milrinone infusion. CONCLUSION: Our results indicate that
      milrinone has some beneficial microcirculatory effects during endotoxemia.
      Although it contributed to systemic hypotension, it attenuated intestinal mucosal
      hypoperfusion.

PMID- 10930210
TI  - Pentobarbital induces nocifensive yhyperreflexia, not hyperalgesia in rats.
AB  - PURPOSE: To seek behavioural, reflexive and histochemical evidence of long
      lasting changes in nociceptive stimulus transmission induced by exposure to doses
      of pentobarbital that induce nocifensive hyperreflexia. METHODS: Nocifensive
      hyperreflexia was induced in 12 rats with 30 mg x kg(-1) pentobarbital ip. Reflex
      latency times for withdrawal of the hind paw from noxious radiant heat were
      measured with an automated electronic timer. Subjective responses to noxious
      stimulation (licking or biting of the stimulated hindpaw) and the level of
      sedation were recorded. Histological sections of lumbar spinal cord were stained
      for immunoreactivity of the immediate-early-gene (IEG), c-fos, in three rats that
      received repeated threshold noxious radiant heat stimulation during the period of
      nocifensive hyperreflexia induced by 30 mg x kg(-1) pentobarbital ip. RESULTS:
      Reflex withdrawal latency decreased by 32 +/- 8% of control values (P < 0.001 )
      following pentobarbital injection and returned to control values 120 min after
      drug injection. Once fully alert, pentobarbital-treated animals did not show any
      increase in nociceptive behaviour relative to saline-injected controls (P =
      0.41). Sustained noxious stimulation to the hindpaw in halothane-anesthetized
      animals was associated with an increase in c-fos immunoreactivity in the dorsal
      horn of the lumbar spinal cord ipsilateral to the stimulation (P < 0.001).
      Threshold stimulation in the pentobarbital-treated animals was not associated
      with any increase in c-fos expression. CONCLUSIONS: During pentobarbital-induced
      hyperreflexia, rats did not show any reflexive, behavioural, or histochemical
      evidence of long-lasting enhancement of nocifensive signal transmission. The
      results are consistent with previous observations that, in the absence of tissue
      injury, nocifensive hyperreflexia induced by barbiturates is a short-lived
      pharmacological effect.

PMID- 10930209
TI  - Propofol inhibits renal cytochrome P450 activity and enflurane defluorination in
      vitro in hamsters.
AB  - PURPOSE: To determine the effect of propofol on renal cytochrome P450 activity
      and defluorination of enflurane. METHODS: Renal microsomes were prepared by
      homogenization and differential centrifugation from pooled hamster kidneys.
      Defluorination of enflurane was assessed by measuring free fluoride metabolites
      after reacting enflurane with renal microsomes incubated with various
      concentrations, 0.05 - 1.0 mmol x L(-1) propofol in the NADPH-generating system.
      Drug metabolizing activities of renal cytochrome P450 mono-oxygenase enzymes were
      evaluated within microsomes preincubated with propofol and reacted with the
      specific marker substrates, aniline, benzo(a)pyrene, erythromycin and
      pentoxyresorufin, for cytochrome P450 2E1, 1A1, 3A4 and 2B1, respectively.
      RESULTS: Renal defluorination of enflurane was inhibited by clinical
      concentrations, 0.05 mmol x L(-1) of propofol (P < 0.05). Dose-dependent
      inhibition of defluorination, aniline and benzo(a)pyrene hydroxylase within
      kidney microsomes was related to propofol concentration. Propofol demonstrated a
      profound inhibition of renal pentoxyresorufin dealkylase activity even at low
      concentrations, 0.05 mmol x L(-1) (P < 0.01). Propofol did not exhibit inhibition
      of erythromycin N-demethylation of kidney microsomes except at high
      concentration, 1.0 mmol x L(-1). Spectral analyses of key coenzymes of renal
      cytochrome P450 monooxygenase, cytochrome b5 and cytochrome c reductase,
      demonstrated an inhibition when incubated with high concentrations of propofol (P
      < 0.05). CONCLUSION: In an in vitro study in an NADPH-generating system of
      hamster kidney microsomes, propofol, in clinical concentrations, exhibited a
      broad-spectrum of inhibition to renal monooxygenase activities and enflurane
      defluorination.

PMID- 10930211
TI  - Interaction among NMDA receptor-, NMDA glycine site- and AMPA receptor
      antagonists in spinally mediated analgesia.
AB  - PURPOSE: The NMDA (N-methyl-D-aspartate) receptor antagonists and the NMDA
      glycine site antagonists given alone have minimal effects on acute nociception.
      In contrast, the AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid)
      receptor antagonists have a major role in acute nociception. We investigated the
      interactions among these three antagonists in acute nociception. METHODS: Sprague
      Dawley rats (250-300 g) were implanted with chronic lumbar intrathecal catheters
      and were tested for their thermal withdrawal response using the hot plate test
      after intrathecal administration of AP-5 (NMDA receptor antagonist), ACEA 1021
      (NMDA glycine site antagonist), or ACEA 2085 (AMPA receptor antagonist). The
      combinations of these three agents were also tested. RESULTS: Intrathecal
      administration of ACEA 2085 had a dose dependent analgesic effect while
      intrathecal AP-5 or ACEA 1021 could not induce dose dependent effect. Co
      administration of AP-5 10 microg and ACEA 2085 intrathecally showed no changes in
      the thermal response latency compared with ACEA 2085 alone. ACEA 1021, 12 microg,
      and AP-5 showed left-ward shift of the dose effect curve only with small doses of
      AP-5 (1 microg, 3 microg). Only the smallest dose of ACEA 2085 (0.1 ng) with ACEA
      1021 12 microg induced antinociception compared with that of ACEA 2085 alone.
      CONCLUSIONS: The combination of the NMDA glycine site antagonist and low doses of
      the NMDA receptor antagonist or the AMPA receptor antagonist increased the
      analgesic effect on acute thermal nociception with increased side effects, while
      the NMDA receptor antagonist and the AMPA receptor antagonist had no such
      interaction.

PMID- 10930212
TI  - Interaction of nitrous oxide and propofol to reduce hypertensive response to
      stimulation.
AB  - PURPOSE: To evaluate the interaction between nitrous oxide and propofol for the
      suppression of hypertension following electrical stimulation of the mental nerve
      in the rabbit. METHODS: Male Japan White rabbits were tracheostomized, cannulated
      and mechanically ventilated under isoflurane anesthesia. Square wave pulses (5 V,
      0.5 msec, 50 Hz for 5 sec) were delivered to the left mental nerve. Animals
      received nitrous oxide 20, 40, 60 and 80% (Group 1); propofol 200, 400, 600 and
      800 microg x kg(-1) min(-1) (Group 2); or combinations of nitrous oxide and
      propofol at 10 + 100, 20 + 200, 30 + 300 and 40 % + 400 microg x kg(-1) x min(-1)
      (Group 3). Systolic blood pressure was recorded from immediately before to
      maximal increase following nerve stimulation. Probit analysis was used to obtain
      ED(50) values for 50% suppression of blood pressure elevation. Isobolographic
      analysis was used to evaluate the interaction between nitrous oxide and propofol.
      RESULTS: ED(50) values are 52.9% for nitrous oxide (Group 1), 464.1 microg x kg(
      1) min(-1) for propofol (Group 2), 21.7 % + 217.1 microg x kg(-1) min(-1) for
      nitrous oxide and propofol combination (Group 3) and 24. 7 % + 247.1 microg x kg(
      1) x min(-1) for the theoretically additive combination of nitrous oxide and
      propofol, respectively. CONCLUSION: The interaction between nitrous oxide and
      propofol for the suppression of blood pressure elevation following electrical
      stimulation of the mental nerve is additive.

PMID- 10930213
TI  - Transfusions in patients undergoing cardiac surgery with autologous blood.
AB  - PURPOSE: Determinants of allogeneic blood use in cardiac surgery include
      preoperative factors such as female sex, age, body weight, hematocrit and red
      cell volume. We verified if these variables also predicted the need for
      allogeneic transfusions when autologous blood is predonated. METHODS: Demographic
      and intraoperative variables, hemoglobin concentrations and transfusion
      requirements in patients undergoing cardiopulmonary bypass with autologous blood
      predonation were reviewed. Multivariate logistic regression and RECPAM tree
      growing analyses were applied to identify the preoperative predictors of
      allogeneic transfusion in these patients. RESULTS: Data from 230 patients
      included in our autologous blood program between 1995 and 1998 were analysed.
      Patients undergoing complex/reoperative surgical procedures and patients over age
      64yr with a low red cell volume (<2070ml) undergoing simple procedures were more
      likely to require allogeneic red cells. Younger patients with a low red cell
      volume undergoing simple procedures carried an intermediate risk. Allogeneic
      transfusion was avoided in 95% of patients undergoing simple procedures when red
      cell volume > or = 2070ml. CONCLUSIONS: In our institution, complex/reoperative
      surgery, low red cell volume and increased age are the main factors associated
      with the need for allogeneic red cell transfusion despite autologous blood
      predonation. Knowledge of the factors that limit the effectiveness of predonation
      with respect to allogeneic blood exposure should help clinicians decide which
      cardiac surgical patients should be included in autologous blood programs.

PMID- 10930215
TI  - Web Page Review: The Anwser Page/Anesthesiology.

PMID- 10930214
TI  - Using computer technology to help keep investigators honest.

PMID- 10930216
TI  - Truth, lies, and the Internet.

PMID- 10930217
TI  - CD ROMs and Anesthesia Machines.

PMID- 10930218
TI  - Assistance for the anesthesiologist--a transatlantic view.

PMID- 10930219
TI  - Fractured laryngeal mask airway (LMA).

PMID- 10930220
TI  - Subcutaneous tunneling of the interscalene catheter.

PMID- 10930221
TI  - Functional outcome of stapled ileal pouch-anal canal anastomosis versus handsewn
      pouch-anal anastomosis.
AB  - This study was conducted to determine whether stapled ileal pouch-anal canal
      anastomosis (IACA) preserving the anal transitional zone (ATZ) or hand-sewn ileal
      pouch-anal anastomosis with mucosectomy (IPAA) is more beneficial in achieving
      disease eradication and better postoperative function. IACA was performed in 10
      patients with ulcerative colitis (UC) and 10 patients with familial adenomatous
      polyposis (FAP), 15 of whom were examined proctoscopically. IPAA was performed in
      4 patients with UC and 8 patients with FAP. The mean maximum resting pressure
      (MRP) was 55 mmHg in the IACA group and 34 mmHg in the IPAA group (P < 0.01). The
      anorectal inhibitory reflex was positive in 18 patients (90%) from the IACA group
      and 5 (42%) from the IPAA group (P < 0.05). The pre- and postoperative MRPs were
      61 mmHg and 55 mmHg, respectively, in the IACA group vs 63 mmHg and 34 mmHg,
      respectively, in the IPAA group (P < 0.01). Whereas 16 (80%) of the 20 IACA
      patients could discriminate feces from gas, only 4 (33%) of the 12 IPAA patients
      could (P < 0.05). The mean observation period was 2.3 years, the mean length of
      the columnar cuff was 2.8 cm, and no case of dysplasia or adenoma was seen.
      Postoperative function is more favorable following IACA than following IPAA, both
      physiologically and symptomatically. However, long-term surveillance of the
      residual mucosa is necessary before making a final recommendation.

PMID- 10930222
TI  - Pathomorphological and histological prognostic factors in curatively resected
      ductal adenocarcinoma of the pancreas.
AB  - The fate of patients with potentially resectable carcinomas is not only
      determined by the pTNM tumor stage, but also possibly by tumor-biological
      factors. The aim of this study was to identify these prognostic factors in
      patients undergoing primary curative (R0) resection. The study retrospectively
      analyzed 113 patients with ductal adenocarcinoma who were operated on between
      1986 and 1995. R0 resection was able to be performed in 93 patients. Lymph node
      metastases were found in 73%. The rates of lymph vessel and perineural invasion
      were 83.5% and 45%, respectively. Among the 25 carcinomas without lymph node
      metastases, 64% already had lymph vessel invasion and 48% had perineural
      invasion. The cumulative 5-year survival rate of the 91 surviving patients
      analyzed was 10.5%. Depending on the tumor stage we found a significant
      difference in 5-year survival rates between patients without lymph node
      metastases (26.5%) and those with lymph node involvement (5%) (P = 0.008). A
      multivariate analysis only identified lymph vessel invasion (L0/1), tumor size (<
      or = or < or =2 cm), and tumor grading (G) to have significant and independent
      prognostic value. Lymph vessel invasion, tumor size, and tumor grading proved to
      be independent factors determining long-term prognosis.

PMID- 10930223
TI  - Management of cholelithiasis in combination with cardiovascular surgery.
AB  - A retrospective review of the perioperative management of patients with
      cardiovascular surgical disorders and cholelithiasis was conducted, and the
      surgical strategies employed are discussed. Between 1988 and 1998, 18 patients
      having cardiovascular surgical disorders underwent cholecystectomy. These
      patients were divided into three groups: group I, given a one-stage operation (n
      = 9); group II, given a two-stage operation (n = 3); and group III, given
      cholecystectomy during follow-up after cardiovascular surgery (n = 6). In group
      I, a median laparotomy was adopted for patients with an abdominal aortic aneurysm
      (AAA) to allow both disorders to be treated through the same incision, whereas a
      right subcostal approach was employed to separate the incisions for patients who
      underwent cardiac operations. In group II, one patient underwent cholecystectomy
      before cardiac surgery, and two patients underwent cholecystectomy for
      postoperative cholecystitis after cardiovascular operations. One patient from
      group II and all from group III were on preoperative anticoagulant therapy, two
      of whom underwent laparoscopic cholecystectomy. No fatal complications such as
      prosthetic infection, intraperitoneal hemorrhage, or cerebral attack were
      encountered. In conclusion, we consider that performing cholecystectomy during
      AAA repair may be safe and prevents the risk of postoperative cholecystitis; it
      is preferable to treat cholelithiasis coexisting with cardiac disorders
      concomitantly with or before cardiac operations; and laparoscopic cholecystectomy
      can be safely performed under anticoagulant therapy.

PMID- 10930224
TI  - Screening for abdominal aortic aneurysms during a basic medical checkup in
      residents of a Japanese rural community.
AB  - To determine the prevalence of abdominal aortic aneurysms (AAA) and the size
      distribution of the abdominal aortic diameter in the Japanese population, 1,591
      residents of a farming community were screened by ultrasonography during the
      annual basic medical checkup arranged by the town. The mean diameter of the
      abdominal aorta was 17.2 +/- 2.2mm and four AAAs were found (0.3%), all in men
      aged 60 years or older, three of whom were hypertensive. The mean diameter of the
      common iliac artery was 10.2 +/- 5.1mm and five iliac arterial aneurysms were
      found (0.3%). One man had both aortic and iliac arterial aneurysms. The iliac
      arterial aneurysms were also found in men, four of whom were aged 60 years or
      older and had a smoking habit. We were able to keep the cost of screening low by
      combining the program with an annual basic medical checkup. These findings
      indicate that it is important to examine the iliac artery as well as the
      abdominal aorta because the incidence of aneurysm is similar in both. Screening
      for AAAs using ultrasonography is accurate enough to detect them before rupture,
      and can be effectively performed in men aged 60 years or older during their
      annual basic medical checkup.

PMID- 10930225
TI  - Distribution of arterial involvement in thromboangiitis obliterans (Buerger's
      disease): results of a study conducted by the Intractable Vasculitis Syndromes
      Research Group in Japan.
AB  - The clinical profile of thromboangiitis obliterans (TAO) has been changing. The
      purpose of this study was to clarify the distribution of arterial involvement in
      this disease, based on a nationwide survey carried out in 1993. A total of 825
      TAO patients with complete records were analyzed. There were 749 men and 76
      women, with a mean age of 50.8 +/- 0.4 years. The survey assessed clinical
      manifestations categorized by Fontaine's classification, distribution of the
      lesions, associated diseases, responses to treatment, and outcome. This study
      focused on the distribution of arterial involvement. There were 42 patients
      (5.1%) with upper-extremity arterial involvement only, 616 (74.7%) with lower
      extremity involvement only, and 167 (20.2%) with both. The most frequently
      affected arteries were the anterior (41.4%) or posterior (40.4%) tibial arteries
      in the lower extremities, and the ulnar artery (11.5%) in the upper extremities.
      There were no significant differences in the distribution of arterial involvement
      between men and women or between the right and left sides. In conclusion,
      approximately 25% of the patients had upper-extremity involvement. The anterior
      or posterior tibial arteries were most commonly affected. There was no
      significant difference in the distribution of arterial involvement between male
      and female patients.

PMID- 10930226
TI  - Experimental study of an artificial esophagus using a collagen sponge, a
      latissimus dorsi muscle flap, and split-thickness skin.
AB  - The time and effort spent trying to devise an artificial esophagus have not yet
      resulted in success, and leakage and strictures at the anastomotic sites remain
      the most frequent complications. We developed an artificial esophagus with a
      bilayered structure made of porous collagen sponge (artificial dermis; AD), a
      latissimus dorsi muscle flap (LD), and split-thickness skin (STS). We
      investigated whether the use of AD prevented the contraction of grafted skin and
      its effects on the extensibility of the neoesophagus in rabbits. We experimented
      with two groups. In the AD group, AD was applied to the surface of the LD. Three
      weeks later, the STS was grafted. In the control group, the STS was grafted
      directly onto the LD. The sizes of the STS in both groups 3 weeks after the graft
      were, respectively, 56.6% +/- 4.1% and 39.0% +/- 10.2% of the initial surface
      area of the STS (P < 0.01). The roll made in the AD group had better
      extensibility than that in the control group. We replaced the cervical esophagus
      in 12 rabbits with the neoesophagus made from AD, STS, and LD. The longest
      survival period was 16 days. Esophagography did not reveal either anastomotic
      leakage or stenosis in any of the five rabbits in the experiments. These findings
      suggested that AD can thus be used to create a more suitable hybrid artificial
      esophagus.

PMID- 10930227
TI  - The significance of MMP-1 and MMP-2 in peritoneal disseminated metastasis of
      gastric cancer.
AB  - The purpose of this study was to clarify the role of the matrix
      metalloproteinases (MMPs), collagenase (MMP-1), and gelatinase A (MMP-2), both of
      which are known to be involved in the development of gastric cancer, in
      peritoneal dissemination. The concentrations of MMP-1 and MMP-2 in the
      supernatant of mixed culture simulated peritoneal dissemination were measured in
      vitro with mesothelial cells and cancer cells using an enzyme-linked
      immunosorbent assay. The concentration of MMP-1 increased significantly after the
      contact culture was mixed with these two cells, in comparison with the non
      contact mixed culture or the mesothelial cell culture alone. These results
      demonstrate that the production of MMP-1 derived from mesothelial cells was
      increased by contact with cancer cells. To clarify the effect of MMP-1 and MMP-2
      on gastric cancer invasion, an invasion assay using matrigel was performed. After
      treatment with anti-MMP-1 monoclonal antibody (mAb) or anti-MMP-2 mAb, the number
      of matrigel-penetrating cancer cells was significantly reduced, indicating that
      MMP-1 and MMP-2 derived from mesothelial cells had a strong reaction to gastric
      cancer invasion. In conclusion, as MMP-1 showed a paracrine-like action
      responding to stimulus from cancer cells, it seemed to play an important role in
      the progression of peritoneal dissemination.

PMID- 10930229
TI  - High-porosity expanded polytetrafluoroethylene grafts for thoracic vena cava
      replacement with or without an omentum wrap.
AB  - We previously reported that, in a short-term thoracic inferior vena cava (IVC)
      replacement, a high-porosity expanded polytetrafluoroethylene (ePTFE) graft
      (fibril length 60 microm) performed well without altering the short-term patency,
      and that the healing of the high-porosity ePTFE graft was accelerated by an
      omentum wrap. The purpose of this study was to examine the long-term performance
      of the high-porosity ePTFE graft with or without an omentum wrap. Eighteen grafts
      were placed as a thoracic IVC replacement in dogs. Nine of the grafts were
      wrapped in an omental pedicle flap while the other 9 were not. At 1 month and 6
      months, the grafts were harvested and examined for a pathological analysis.
      During the observation period, one dog died of a viral infection, while the other
      17 dogs survived. At 1 month and 6 months, the patency rates of the 17 grafts
      were 100% regardless of the presence or absence of an omentum wrap. The healing
      of the grafts without omentum wrap was incomplete 6 months after implantation;
      granulation tissue was present in the center of the pseudointima. The grafts
      healed completely by the addition of an omentum wrap. Our data suggest that, with
      an omentum wrap, the high-porosity ePTFE graft is fully expected to show a good
      long-term function.

PMID- 10930228
TI  - Changes in the expression of lipid-mediated signal-transducing enzymes in the rat
      liver after partial hepatectomy.
AB  - Prostaglandins (PGs), metabolites of arachidonic acid, and other lipid mediators
      produced by phospholipases C (PLC) and D (PLD) are thought to play important
      roles in hepatocyte proliferation. The present study examined lipid-mediated
      signaling in the rat liver after partial hepatectomy (PH). Rats were killed 1-48
      h after 70% PH and the remaining liver tissue was removed. The mRNA and protein
      levels of some signaling molecules were measured by reverse transcriptase
      polymerase chain reaction (RT-PCR) and Western blotting, respectively. The levels
      of hepatocyte growth factor (HGF) mRNA showed a biphasic change, peaking 3 h and
      9 h after PH. The expression of PLCdelta4 peaked at 12 h, but no significant
      changes in the expression of PLCbeta1 and PLCgamma1 were seen after PH. T he
      enzymes involved in PG production, namely, the expression of cytosolic PLA2 and
      cyclooxygenase 1 (COX1), remained constant after PH. However, the mRNA of COX2
      increased transiently at 3 h, and Western blot analysis showed an increase in
      COX2 protein at 12 h. The expression of PLD1b peaked at 9 h and PLD1a at 12 h,
      whereas the expression of PLD2 remained consistent for 24 h. These results
      suggest that transcriptional controls may act for PLCdelta4, PLD1a/b, and COX2
      during hepatocyte regeneration after PH.

PMID- 10930230
TI  - Co-occurrence of mucoepidermoid carcinoma and squamous cell carcinoma of the
      esophagus: report of a case.
AB  - A case of co-occurrence of a mucoepidermoid carcinoma (MEC) and a squamous cell
      carcinoma (SCC) in the esophagus is described. The present patient was a 61-year
      old man who underwent a curative esophagectomy with a regional lymph node
      dissection for a MEC in the lower esophagus and a SCC near the esophagogastric
      junction. The two lesions were endoscopically and histologically divided by a
      normal esophageal mucosa. The MEC of the esophagus consisted of SCC cells and
      signet-ring cells, and a mucin product and carcinoembryonic antigen, which were
      found at high levels in the blood serum before surgery, were detected
      histochemically in the signet-ring cells. The follow-up survey of the patients
      with esophageal MEC previously reported in Japan showed that most of the patients
      died of either local recurrence or widespread metastasis after treatment; the
      overall 5-year survival rate was 24.4% in the total 25 cases, and 27.7% in the 22
      resected cases. However, 6 patients who died of therapeutic complications were
      included among these patients; furthermore, the 5-year survival rate after
      surgery was 29.2% in the patients treated over the last decade (1989-1998). We
      expect that the clinical outcome of patients treated for esophageal MEC will
      therefore improve in the future.

PMID- 10930231
TI  - Adenosquamous carcinoma of the remnant stomach: report of a case.
AB  - We report herein the case of a 59-year-old man found to have adenosquamous
      carcinoma of the remnant stomach which demonstrated rapid progression. The
      patient was admitted to our hospital to undergo surgery for a papillary tumor of
      the remnant stomach. Total resection of the remnant stomach with lymph node
      dissection was performed, and pathological examination confirmed a diagnosis of
      adenosquamous carcinoma with invasion into the muscularis propria and lymph node
      metastasis around the perigastric areas. Multiple liver metastases were found 6
      months after the operation, for which a right hepatectomy was performed with
      curative intent; however, he died 2 months later due to lymphangitis
      carcinomatosa of the lung.

PMID- 10930232
TI  - Hepatic portal venous gas: report of a case.
AB  - Hepatic portal venous gas is easily diagnosed radiographically by the appearance
      of tubular lucencies branching horizontally from the porta hepatis and extending
      to within 2cm of the liver capsule. Associated conditions vary from benign to
      potentially lethal diseases which require emergency operations. A case of hepatic
      portal venous gas secondary to small bowel obstruction is presented and a review
      of the literature is also provided.

PMID- 10930233
TI  - Nonfunctioning endocrine tumor of the pancreas with extrapancreatic growth and
      cyst formation: report of a case.
AB  - We report a case of nonfunctioning endocrine tumor of the pancreas with
      extrapancreatic growth and cyst formation. A 48-year-old woman was admitted to
      our hospital with an upper abdominal mass, which was detected during a routine
      medical checkup. The preoperative diagnosis was a solid cystic tumor of the
      pancreas. The tumor, which measured about 7cm in diameter, arose from the head of
      the pancreas and had a thin stalk, measuring about 1 cm in diameter. The
      histopathological diagnosis was a malignant nonfunctioning endocrine tumor of the
      pancreas. Cyst formation occurred in 67% of the reported cases with
      extrapancreatic growth in Japan. It is speculated that the cyst formation in this
      disease is related to the large size of the tumor and to the extrapancreatic
      growth.

PMID- 10930234
TI  - Adenoid cystic carcinoma of the breast: report of a case.
AB  - Adenoid cystic carcinoma of the breast is an uncommon form of cancer, and only a
      few articles have described the cytological findings of this disease. We report
      herein the case of a 48-year-old woman who presented with a breast mass beneath
      the nipple, the aspirate from which consisted of globules of mucous balls
      surrounded by epithelial cells with scant cytoplasm and hyperchromatic nuclei.
      Microscopically, the tumor was formed by myoepithelial cells and glandular
      epithelial cells in a biphasic pattern. Immunohistochemical study revealed
      positivity for smooth muscle actin. A left total mastectomy with axillary lymph
      node dissection was performed. None of the 22 axillary lymph nodes contained
      metastases, and the patient remains well and free from recurrence 29 months after
      her operation. This case report provides some information about the cytological
      diagnosis and the accuracy of fine-needle aspiration, which must be considered
      despite the rarity of this disease.

PMID- 10930235
TI  - Granular cell tumor of the male breast: report of a case.
AB  - We treated a 35-year-old male with a granular cell tumor in the right breast.
      Physical examination revealed a solid, flattened, round 3.2 x 2.5-cm mass with an
      irregular surface, covering skin fixation and right axillary lymphadenopathy.
      Mammography revealed a well-demarcated high-density mass with a minimal starburst
      appearance. Ultrasonography revealed a hypoechoic, nonhomogeneous mass with an
      acoustic shadow. Several enlarged lymph nodes in the right axilla were removed at
      the time of breast tumor excision. Histologically, the tumor featured nests of
      round or polygonal cells with abundant eosinophilic cytoplasmic granules and
      small round nuclei, and the enlarged lymph nodes in the right axilla exhibited no
      metastasis. Immunohistochemically, there was positive staining for S-100 protein,
      neuron-specific enolase, and vimentin. The tumor also stained for macrophage CD
      68, alpha1-antichymotrypsin, and myoglobin. These immunohistochemical findings
      suggested the tumor cells to be undifferentiated mesenchymal cells which
      demonstrated the properties of neurogenic cells and histiocytes.

PMID- 10930236
TI  - Acute arterial thrombosis with antithrombin III deficiency in nephrotic syndrome:
      report of a case.
AB  - Nephrotic syndrome frequently causes venous thromboembolic complications.
      Arterial thrombosis has rarely been reported and is mainly observed in children.
      Only six cases of lower extremity arterial thrombosis in adults have been
      reported in the literature. The outcome in these cases was unsatisfactory because
      of the high rates of limb loss and recurrence of thrombosis. We report successful
      treatment of a 39-year-old man who suffered from right lower extremity arterial
      thrombosis associated with decreased levels of serum antithrombin III. He was
      admitted to our hospital with severe pain in his right foot. No pulse was
      palpable in his right dorsalis pedis or posterior tibial arteries. His right foot
      was cold and mottled, with a reduced sensation and motor activity. The laboratory
      data revealed a serum total protein concentration of 3.9g/dl and an albumin
      concentration of 1.5 g/dl. The coagulation profile showed a fibrinogen level of
      879 mg/dl and antithrombin III value of 9.5%. Right lower extremity arteriography
      showed a complete occlusion of the right deep femoral artery and popliteal
      artery, and a filling defect in the common femoral artery. An emergency
      thrombectomy was performed under general anesthesia. The patient was treated
      successfully, and surgical treatment was followed by anticoagulant therapy with
      1,000 units of antithrombin III. A renal biopsy revealed histologic evidence of
      minimal change of glomerulonephritis. He was discharged 3 months later, and no
      recurrence of thrombosis has yet been observed.

PMID- 10930237
TI  - Intracystic hemorrhage of pancreatic serous cystadenoma after renal
      transplantation: report of a case.
AB  - Immunosuppressive therapy after transplantation increases the risk of developing
      neoplasms, and neoplasms of the digestive organs are very common in Asia. We
      experienced a patient with an intracystic hemorrhage of pancreatic serous
      cystadenoma during the follow-up after renal transplantation. Pancreatic
      cystadenomas are not frequent. Only two cases, presenting with acute abdomen,
      have so far been reported in the literature. The intracystic hemorrhage in our
      case may have been related to a rapid tumor growth due to weakened antitumor
      immunity and azathioprine-induced pancreatitis.

PMID- 10930238
TI  - Synthesis of enantiopure termini-differentiated heptane stereotriads. Application
      to side chain-functionalized tetrahydrofurans of IKD-8344.
AB  - Enantiopure epoxy cycloheptenyl sulfones syn-7b and anti-7b are prepared in five
      high-yielding and stereospecific operations from 1, 3-cycloheptadiene. These
      substrates serve as effective precursors for cis- and trans-substituted
      tetrahydrofurans (12, 10) which are segments of the antineoplastic agent IKD
      8344.

PMID- 10930239
TI  - Diastereoselective protonation of lactam enolates derived from (R)
      phenylglycinol. A novel asymmetric route to 4-phenyl-1,2,3, 4
      tetrahydroisoquinolines.
AB  - Highly diastereoselective protonation of chiral lactam enolates of 4-substituted
      1,4-dihydroisoquinolin-3-ones is reported. Protonation and alkylation processes
      of these lactam enolates derived from phenylglycinol occur with opposite
      diastereofacial selectivity. This diastereoselective protonation has been applied
      to the asymmetric synthesis of (4S)-N-methyl-4-phenyl-1,2,3,4
      tetrahydroisoquinoline 9 obtained in up to 97% ee.

PMID- 10930240
TI  - Control of olefin geometry in the bryostatin B-ring through exploitation of a
      C(2)-symmetry breaking tactic and a Smith-Tietze coupling reaction.
AB  - A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon
      for the bryostatin family of antitumor agents is reported. Noteworthy features of
      our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13
      en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion
      of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to
      epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson
      etherification reaction completed the synthesis of 2.

PMID- 10930241
TI  - Asymmetric construction of quaternary carbon centers by regio- and
      enantiocontrolled allylzincation
AB  - An allylic zinc reagent bearing a chiral bisoxazoline ligand adds to a
      substituted cyclopropenone acetal to produce an optically active cyclopropanone
      acetal possessing a quaternary chiral center in high yield with 97.8-99.8% ee.
      The steric effects of the bulky bisoxazoline ligand overwhelm the
      regioselectivity inherent to the electronic property of the olefinic acceptor.
      High pressure exerts favorable effects on the reaction rate without affecting the
      high enantio- or regioselectivity.

PMID- 10930243
TI  - Kinetic isotope effects for the C-H activation step in phase-transfer
      halogenations of alkanes
AB  - Within the scope of phase-transfer halogenations (Br and I) of alkanes,
      significant H/D kinetic isotope effects (KIE = 4-5) indicate that hydrogen
      abstraction is rate limiting. The excellent agreement of computed and
      experimentally determined H/D KIE as well as trapping experiments support the
      involvement of trihalomethyl radicals in the activation step.

PMID- 10930245
TI  - Mechanistic aspects of palladium-catalyzed allylstannylation of alkynes
AB  - An alpha-methylallylstannane added to an alkyne in the presence of a palladium
      catalyst with perfect regioselectivity both in the allylic and alkynic moieties.
      Comparison of the reaction of isomeric butenylstannanes suggests two catalytic
      cycles, one of which includes a palladacyclopentene intermediate and beta-tin
      elimination pathway.

PMID- 10930244
TI  - Soluble polymer bound cleavage reagents: a multipolymer strategy for the cleavage
      of tertiary amines from REM resin.
AB  - Soluble polymer bound reagent 1 has been prepared to cleave tertiary amines from
      REM resin. Normally, amines cleaved from REM resin require extraction or
      chromatography to remove excess cleavage reagent and its byproducts. The
      solubility profile of non-crosslinked polystyrene (NCPS) based reagent 1
      eliminates the need for such purification and allows for the direct isolation of
      a library of pure tertiary amines through simple filtration and concentration
      operations.

PMID- 10930246
TI  - Enantiospecific and regioselective rhodium-catalyzed allylic alkylation:
      diastereoselective approach to quaternary carbon stereogenic centers.
AB  - The enantiospecific and regioselective rhodium-catalyzed allylic alkylation of a
      series of chiral nonracemic allylic carbonates, followed by ozonolysis and
      reductive lactonization, provides a convenient route to optically active gamma
      lactones. Sequential alkylation and reductive alkylation furnished the alpha
      quaternary-beta-ternary substituted gamma-lactone derivative as a >/=10:1 mixture
      of diastereoisomers.

PMID- 10930242
TI  - Cross-coupling of hydroxycinnamyl aldehydes into lignins.
AB  - Pathways for hydroxycinnamyl aldehyde incorporation into lignins are revealed by
      examining transgenic plants deficient in cinnamyl alcohol dehydrogenase, the
      enzyme that converts hydroxycinnamyl aldehydes to the hydroxycinnamyl alcohol
      lignin monomers. In such plants the aldehydes incorporate into lignins via
      radical coupling reactions. As diagnostically revealed by long-range (13)C-(1)H
      correlative NMR, sinapyl aldehyde (3, 5-dimethoxy-4-hydroxy-cinnamaldehyde) 8-O-4
      cross-couples with both guaiacyl (3-methoxy-4-hydroxyphenyl-propanoid) and
      syringyl (3, 5-dimethoxy-4-hydroxyphenyl-propanoid) units, whereas coniferyl
      aldehyde cross-couples only with syringyl units.

PMID- 10930247
TI  - Helical tetrathiafulvalene oligomers. Synthesis and properties of Bi-, ter-, and
      quatertetrathiafulvalenes
AB  - A series of fully methylthiolated bi-, ter-, and quatertetrathiafulvalenes have
      been synthesized using cross- and homocoupling reactions of
      tetrathiafulvalenylzinc derivatives; the tetracation-tetraradical derived from
      the helical tetrathiafulvalene tetramer exhibits an intramolecular association of
      the terminal cation-radicals.

PMID- 10930248
TI  - Primary amides. A general nitrogen source for catalytic asymmetric
      aminohydroxylation of olefins.
AB  - N-Bromo,N-lithio salts of primary carboxamides have been shown to be efficient
      nitrogen sources for catalytic asymmetric aminohydroxylation of olefins, behaving
      much like the parent N-bromoacetamide in these reactions. alpha-Chloro-N
      bromoacetamide is a particularly interesting nitrogen source, as it is
      functionalized for further reaction, including easy deprotection by treatment
      with thiourea.

PMID- 10930249
TI  - Palladium-catalyzed intramolecular coupling of vinyl halides and ketone enolates.
      Synthesis Of bridged azabicyclic compounds
AB  - The palladium-mediated intramolecular coupling of amino-tethered vinyl halides
      and ketone enolates is a useful methodology for the synthesis of nitrogen
      heterocycles and constitutes a new synthetic entry to the 2
      azabicyclo[3.3.1]nonane framework. A study about the reaction conditions and the
      scope of the process is reported.

PMID- 10930250
TI  - A highly efficient asymmetric synthesis of optically active alpha, gamma
      substituted gamma-butyrolactones using a chiral auxiliary derived from
      isosorbide.
AB  - Using an easily accessible and inexpensive chiral auxiliary derived from
      isosorbide, optically active alpha,gamma-substituted gamma-butyrolactones were
      obtained in high enantiomeric purity (up to >99% ee for trans) by the SmI(2)
      induced reductive coupling of chiral methacrylate 7 with ketones in the presence
      of (-)-sultam as a proton source.

PMID- 10930251
TI  - Amidation of saturated C-H bonds catalyzed by electron-deficient ruthenium and
      manganese porphyrins. A highly catalytic nitrogen atom transfer process.
AB  - Amidation of a variety of hydrocarbons with PhI=NTs catalyzed by ruthenium and
      manganese meso-tetrakis(pentafluorophenyl)porphyrins 1 and 2 afforded N
      substituted amides in up to 92% yields with good to excellent substrate
      conversions. By employing catalyst 2, exceptionally high turnovers (up to 2600)
      were achieved, and the amidations can be effected by directly using
      PhI(OAc)(2)/NH(2)R as amidating reagents; in the case of R = COCF(3) a direct
      amination was realized in up to 90% yield.

PMID- 10930252
TI  - Acid-promoted rearrangement of carbonate functionality anchored to the lower rim
      of a Calix
AB  - A unique calix[4]arene lower-rim intramolecular rearrangement, resulting in
      molecular asymmetry arising from the upper- and lower-rim substitution pattern,
      produces a new class of inherently chiral calix[4]arenes in a partial cone
      conformation. This was aided by molecular rigidification arising from pi-pi and C
      H.pi interactions between bulky lower-rim substituents, with the corresponding
      circular dichroism spectra exhibiting the most intense bisignate Cotton effects
      yet observed for calix[4]arenes not bearing a chiral center.

PMID- 10930253
TI  - 3He NMR study of (3)He@C(60)H(6) and (3)He@C(70)H(2)(-)(10)
AB  - The (3)He NMR of (3)He@C(60)H(6), (3)He@C(70)H(2), (3)He@C(70)H(4),
      (3)He@C(70)H(8), and (3)He@C(70)H(10) have been investigated. A new, unidentified
      C(60)H(6) isomer has been found by using (3)He NMR. (3)He@C(70)H(10) shows the
      most downfield-shifted (3)He NMR resonance among the neutral C(70) derivatives.

PMID- 10930254
TI  - Isotope effects and syn selectivity in the ene reaction of triazolinedione with
      conjugated enones: aziridinium imide or an open intermediate mechanism?
AB  - The ene reaction of 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) with phorone-d(6)
      (5-d(6)) shows an inverse beta-secondary isotope effect and with mesityl oxide
      d(3) (7-d(3)) proceeds with 93% syn selectivity. These results are consistent
      with a mechanism involving the formation of an aziridinium imide intermediate in
      the rate-determining step. An open biradical or dipolar intermediate is excluded
      by them.

PMID- 10930255
TI  - Copper-catalyzed aminohalogenation using the 2-NsNCl(2)/2-NsNHNa combination as
      the nitrogen and halogen sources for the synthesis of anti-alkyl 3-chloro-2-(o
      nitrobenzenesulfonamido)-3-arylpropionates.
AB  - New regio- and stereoselective aminohalogenation of cinnamic esters has been
      developed using the combination of 2-NsNCl(2)/2-NsNHNa as the nitrogen and
      chlorine sources and copper(I) triflate as the catalyst. The new procedure
      provides an efficient synthesis of anti-alkyl 3-chloro-2-(o
      nitrobenzenesulfonamido)-3-phenylpropionate derivatives. Nine examples are
      presented with good yields (62-82%) and stereoselectivity ((5:1)-(30:1)).

PMID- 10930256
TI  - Comparison of the effects of 5- and 6-HOAt on model peptide coupling reactions
      relative to the cases for the 4- and 7-Isomers.
AB  - Synthesis of 5- and 6-HOAt has completed the full set of the four HOAt isomers
      derived from HOBt by insertion of a single nitrogen atom in the benzenoid
      nucleus. Comparison of the reactivity of all four isomers in model peptide
      coupling reactions has confirmed the unique character of the 7-isomer in
      promoting selectivity and maintaining configuration at the reactive carboxylic
      acid residue.

PMID- 10930257
TI  - Arabidopsis thaliana LUP1 converts oxidosqualene to multiple triterpene alcohols
      and a triterpene diol.
AB  - The Arabidopsis thaliana LUP1 gene encodes an enzyme that converts oxidosqualene
      to pentacyclic triterpenes. Lupeol and beta-amyrin were previously reported as
      LUP1 products. Further investigation described here uncovered the additional
      products germanicol, taraxasterol, psi-taraxasterol, and 3,20-dihydroxylupane.
      These results suggest that the 80 known C(30)H(50)O compounds that are
      structurally consistent with being oxidosqualene cyclase products may be derived
      from fewer than 80 enzymes and that some C(30)H(52)O(2) compounds may be direct
      cyclization products of oxidosqualene.

PMID- 10930258
TI  - Steric bulk at cycloartenol synthase position 481 influences cyclization and
      deprotonation.
AB  - Cycloartenol synthase converts oxidosqualene to the pentacyclic sterol precursor
      cycloartenol. An Arabidopsis thaliana cycloartenol synthase Ile481Val mutant was
      previously shown to produce lanosterol and parkeol in addition to its native
      product cycloartenol. Experiments are described here to construct Phe, Leu, Ala,
      and Gly mutants at position 481 and to determine their cyclization product
      profiles. The Phe mutant was inactive, and the Leu mutant produced cycloartenol
      and parkeol. The Ala and Gly mutants formed lanosterol, cycloartenol, parkeol,
      achilleol A, and camelliol C. Monocycles comprise most of the Gly mutant product,
      showing that an alternate cyclization route can be made the major pathway by a
      single nonpolar mutation.

PMID- 10930259
TI  - Solid-phase synthesis of new S-glycoamino acid building blocks.
AB  - Efficient synthesis of unprotected S-glycoamino acid building blocks in the solid
      phase by coupling a sugar 1-thiolate with iodine activated fluoren-9
      ylmethoxycarbonyl (Fmoc) protected amino acids.

PMID- 10930260
TI  - Synthesis of dipolar nitronyl nitroxides
AB  - The synthesis of a nitronyl nitroxide radical with a dipolar (mesomeric betaine)
      unit is reported.

PMID- 10930261
TI  - Expanded scope in ethylene-alkyne cross-metathesis: coordinating heteroatom
      functionality at the propargylic position.
AB  - The Grubbs 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene-substituted ruthenium
      complex 1 catalyzed ethylene-alkyne cross-metathesis and was shown to tolerate
      free hydroxyl groups and coordinating functionality at the propargylic and
      homopropargylic positions. Hindered and enantiomerically enriched 1-substituted
      alkynes also react efficiently under the reported conditions.

PMID- 10930262
TI  - Differential reactivity of alpha- and beta-anomers of glycosyl acceptors in
      glycosylations. A remote consequence of the endo-anomeric effect?
AB  - When phenyl tri-O-benzyl-1-thio-beta-D-galactopyranosiduronic acid esters were
      coupled with a 1/1 mixture of alpha and beta 2,3 di-O-protected D
      galactopyranosiduronic acid esters, the beta-anomer proved to be more reactive.
      Data from theoretical calculations suggested that the enhanced reactivity of this
      anomer compared with the alpha one would be due to a stronger hydrogen bond of
      the C-4 OH with the ring oxygen.

PMID- 10930263
TI  - Ambident effect of a p-sulfinyl group for the introduction of two carbon
      substituents to phenol rings: a convergent synthesis of diverse benzofuran
      neolignans.
AB  - A convergent synthesis of diversely substituted benzofuran neolignans (8) is
      described employing a single p-sulfinyl group on the phenols (3) as an ambident
      functional group for two types of carbon-carbon bond-forming reactions: (i) the
      direct synthesis of the dihydrobenzofuran skeletons through an aromatic Pummerer
      type reaction and (ii) the ipso-substitution of the sulfur functional group by
      carbon substituents through a ligand exchange reaction.

PMID- 10930264
TI  - A facile synthesis of polysubstituted pyrroles.
AB  - alpha-Aminoalkylcuprates prepared from CuX.2LiCl (X = Cl, CN) and 1 equiv of an
      alpha-lithiocarbamate undergo conjugate addition reactions to alpha,beta-alkynyl
      ketones in moderate to good yields, affording E:Z mixtures of alpha,beta-enones.
      Treatment of the conjugate adducts with PhOH/TMSCl in CH(2)Cl(2) effected
      carbamate deprotection and cyclization to afford a flexible two-step synthesis of
      substituted pyrroles.

PMID- 10930265
TI  - Synthesis of geranyl S-thiolodiphosphate. A new alternative substrate/inhibitor
      for prenyltransferases.
AB  - The tris(tetra-n-butylammonium) salt of thiopyrophosphate 5 was prepared from
      trimethyl phosphate in four steps. Treatment of geranyl bromide with 5 gave an
      80% yield of geranyl S-thiolodiphosphate (6). Thiolodiphosphate 6 is
      substantially less reactive than geranyl diphosphate (7) in the prenyl transfer
      reaction catalyzed by farnesyl diphosphate synthase and is a good inhibitor of
      the enzyme.

PMID- 10930266
TI  - Synthesis of two conformationally constrained analogues of the minor tobacco
      alkaloid anabasine.
AB  - The anabasine analogues spiro[4-azaindan-1,2'-piperidine] (7) and spiro[6
      azaindan-1,2'-piperidine] (8) have been prepared. A series of palladium-catalyzed
      reactions, where an intramolecular cyclization constituted a key reaction, were
      utilized for the preparation of the two target compounds.

PMID- 10930267
TI  - Ni(II)/Zn-Mediated chemoselective arylation of aromatic aldehydes: facile
      synthesis of diaryl carbinols
AB  - Direct arylation of aromatic aldehydes with aryl bromides in the presence of
      Ni(II)/Zn was investigated. The choice of ligand in this nickel-catalyzed
      coupling was critical to the formation of the secondary alcohols. Monodentate
      phosphine ligands were ineffective, whereas NiBr(2)(dppe)/Zn successfully
      catalyzed this reductive coupling reaction. The reaction conditions were mild and
      diarylcarbinols with a variety of functional groups such as ketone, ester, amide,
      and nitrile groups were readily prepared.

PMID- 10930268
TI  - [3 + 2]-cycloaddition of nonstabilized azomethine ylides. 10. An efficient
      strategy for the construction of x-Azatricyclo[m.n.0. 0]
AB  - Various new structural entities related to x-azatricyclo[m.n.0.
      0(a)()(,)(b)()]alkanes are constructed by the intramolecular [3 + 2] dipolar
      cycloaddition of nonstabilized cyclic azomethine ylides. The ylide is generated
      by the sequential double desilylation of N-alkyl alpha,alpha'
      bis(trimethylsilyl)cyclic amines using Ag(I)F as a one-electron oxidant.

PMID- 10930269
TI  - Formation of grignard reagents from aryl halides: effective radical probes hint
      at a nonparticipation of dianions in the mechanism
AB  - We have prepared highly efficient radical probes 2a-b involving the hex-5-enyl
      rearrangement. The reaction of 2a-b with active magnesium leads to the cyclized
      products 4a-b, providing a direct evidence of radical intermediates during the
      formation of aryl Grignard reagents. The variations of yields for cyclized
      products 4a-b as a function of structural modifications in 2a-b suggest that the
      intervention of dianions is not necessary to explain the observed results.

PMID- 10930271
TI  - Berberine cation: A fluorescent chemosensor for alkanes and other low-polarity
      compounds. An explanation of this phenomenon
AB  - Alkanes in the presence of berberine sulfate provide an enhancement of
      fluorescent signal, which depends on alkane concentration and structure, when the
      system is irradiated with monochromatic UV light. Computational analysis suggests
      that an ion-induced dipole between alkanes and berberine sulfate is responsible
      for this phenomenon. This interaction can properly model the experimentally
      obtained fluorescent response. The proposed explanation allows other interacting
      systems to be designed, which have been experimentally confirmed.

PMID- 10930270
TI  - The first directed reduction of beta-alkoxy ketones to anti-1,3-diol monoethers:
      identification of spectator and director alkoxy groups.
AB  - A new reduction procedure for the stereoselective reduction of certain beta
      alkoxy ketones is described. The method relies upon electron-transfer reduction
      using samarium diiodide in THF with MeOH as an additive. Reduction is facile for
      a number of alkoxy groups that can complex samarium effectively but is not
      observed with TBS or benzyl protecting groups. Experiments with deuterated
      methanol show that the stereoselectivity arises from protonation of a samarium
      carbanion intermediate.

PMID- 10930272
TI  - A new photocleavable linker in solid-phase chemistry for ether cleavage
AB  - We have designed a new linker (1) for the solid-phase synthesis that cleaves
      ether bonds photolytically. The linker was prepared in nine steps and anchored to
      the support via an amide bond. Photocleavage is a two-step process in which the
      immobilized alcohols are released by photolytic generation of a radical that
      undergoes a spontaneous beta-bond scission. The pivaloyl linker (1) was found to
      cleave off alcohols in high yields and purities. Only traces of acid (pH
      approximately 5.5) are necessary for an efficient cleavage.

PMID- 10930273
TI  - Rhodium-catalyzed ring opening of vinyl epoxides with alcohols and aromatic
      amines
AB  - [Rh(CO)(2)Cl](2) is an effective catalyst for the ring opening of vinyl epoxides
      with alcohols and aromatic amines under neutral conditions at room temperature.
      The reaction occurs with excellent diastereo- and regioselectivity (>20:1) giving
      the trans-1,2-amino alcohols or alkoxy alcohols for a wide range of substrates.
      The regio- and stereochemistry of these reactions is complementary to that
      typically obtained with palladium-catalyzed ring openings of vinyl epoxides.

PMID- 10930274
TI  - Asymmetric total synthesis of (+)-aphanamol I based on the transition metal
      catalyzed [5 + 2] cycloaddition of allenes and vinylcyclopropanes.
AB  - A concise asymmetric total synthesis of (+)-aphanamol I is described, based on
      the transition metal catalyzed [5 + 2] allenyl-vinylcyclopropane cycloaddition.
      The key cycloaddition precursor is convergently assembled from (R)-(+)-limonene
      and cyclopropane diester through a novel decarboxylative dehydration reaction.
      The metal-catalyzed [5 + 2] cycloaddition of this precursor proceeds with
      complete chemo, endo/exo, and diastereoselectivity in 93% yield, representing an
      effective general route to bicyclo[5.3.0]decane derivatives.

PMID- 10930275
TI  - Synthesis of cyclic sulfonamides via intramolecular copper-catalyzed reaction of
      unsaturated iminoiodinanes.
AB  - Olefinic primary sulfonamides were treated with iodobenzene diacetate and
      potassium hydroxide in methanol to give intermediate iminoiodinanes. Catalytic
      copper(I) or (II) triflate then provided intramolecular nitrene delivery leading
      to aziridine formation except in one case where a rare copper-catalyzed C-H
      insertion was observed. The aziridines could be opened by various nucleophiles
      (methanol, thiophenol, allylmagnesium bromide, benzylamine) to give the
      corresponding substituted cyclic sulfonamides.

PMID- 10930276
TI  - Synthesis of 2,3-dihydroisoxazoles from propargylic N-hydroxylamines via Zn(II)
      catalyzed ring-closure reaction
AB  - A novel cyclization reaction of propargylic N-hydroxylamines to 2,3, 5
      trisubstituted 2,3-dihydroisoxazoles in the presence of catalytic amounts (10 mol
      %) of ZnI(2) and DMAP is reported. The methodology provides a mild new approach
      to this useful class of substituted heterocycles that complements extant methods.
      The unique reactivity of the propargylic N-hydroxylamine substrates in the
      presence of Zn(II) and DMAP may have additional applications in other, related
      alkyne cyclization reactions.

PMID- 10930277
TI  - Solvent-dependent stabilization of the E configuration of propargylic secondary
      amides.
AB  - Secondary amides typically exist 98-99% in the Z rotamer to avoid steric
      repulsion between the substituent on the carbonyl carbon and the nitrogen. In
      contrast, secondary amide 3a displays 24% E rotamer at room temperature in
      aqueous solution. The analogous ester displays 6% E rotamer in chloroform, which
      suggests that the relatively high E conformer population observed for 3a in water
      results in part from the low steric bulk of the sp-hybridized carbons and in part
      from the hydrophobic effect.

PMID- 10930278
TI  - Annulation of ketones with vinamidinium hexafluorophosphate salts: an efficient
      preparation of trisubstituted pyridines.
AB  - alpha-Aryl ketones react with vinamidinium hexafluorophosphate salts to give
      access to the corresponding 3-arylpyridines. The annulation reactions proceed in
      good to excellent yields with vinamidinium salts containing electron-withdrawing
      groups at the beta-position (R(2)). The reaction was applied to the preparation
      of the COX-2 specific inhibitor 5-chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5
      pyridinyl)pyridine (1), as well as a series of analogues.

PMID- 10930279
TI  - pH-controlled inclusion and release of oxyanions by dendrimers bearing methyl
      orange moieties.
AB  - We report the synthesis of POPAM dendrimers, bearing up to 64 chromophores at
      their periphery. For these dendrimers, a radiotracer technique was used to study
      the liquid-liquid partition of pertechnetate and (14)C-labeled nucleotides in
      trichloromethane-aqueous systems. Inclusion and release of guest molecules can be
      controlled by changing the pH. The extraction efficacy increases with rising
      generation number.

PMID- 10930280
TI  - Application of trimethylvinylsilane as a convenient synthetic precursor of
      (Perfluoroalkyl)ethenes: An unusual fluoride-induced elimination-desilylation
      coupled reaction
AB  - A convenient and effective method for the preparation of perfluoroalkylated
      ethenes is described. First, the free radical addition of perfluoroalkyl iodides
      to trimethylvinylsilane in the presence of AIBN gave iodoethylsilane
      intermediates (F(CF(2))(n)()CH(2)CHISiMe(3), n = 4 (1), 6 (2), 8 (3), 10 (4); 94
      99%). Then an unusual dehydrohalogenation-desilylation reaction was effected by
      tetrabutylammonium fluoride, and finally the product isolation
      (F(CF(2))(n)()CH=CH(2) (5-8), 62-87%) was facilitated using a fluorous phase
      separation technique. This novel approach can also be applied to adjust short
      C(2) hydrocarbon units to functionalized fluorinated segments (e.g.,
      HOCH(2)(CF(2))(8)CH=CH(2) (11), 71%). All structures were verified by state-of
      the-art multinuclear one- and two-dimensional NMR experiments involving both homo
      ((19)F-(19)F) and heteronuclear ((1)H-(13)C, (19)F-(13)C) correlations based on
      the GMQFCOPS and inverse (1)H and/or (19)F detected GHSQC, GHMQC sequences with
      broad-band adiabatic (13)C decoupling.

PMID- 10930281
TI  - Synthesis of an orange anthrathiophene pigment isolated from a Japanese bryozoan.
AB  - A short, regiospecific synthesis of the naturally occurring anthrathiophene 1
      from naphthazarin (7) is described.

PMID- 10930282
TI  - Synthesis and properties of 9-alkyl- and 9-Arylcyclopenta
AB  - Two strategies for the synthesis of cyclopenta[a]phenalenes are described. NMR, X
      ray diffraction, and cyclic voltammetry studies of simple alkyl- and aryl
      substituted derivatives are reported for the first time.

PMID- 10930283
TI  - A facile highly regio- and stereoselective preparation of N-tosyl allylic amines
      from allylic alcohols and tosyl isocyanate via Palladium(II)-catalyzed
      aminopalladation-beta-heteroatom elimination
AB  - The high regio- and stereoselectivity have been obtained from the allylic
      substitution reaction catalyzed by palladium(II) species. From allylic alcohols,
      one-pot reaction with tosyl isocyanate followed by palladium(II)-catalyzed
      allylic substitution gives N-tosyl (E)-allylic amines in high yield. The
      substitution occurs only at the gamma-position of the 1- or 3-substituted allylic
      alcohols.

PMID- 10930285
TI  - The tri-pi-methane rearrangement: mechanistic and exploratory organic
      photochemistry(1)
AB  - The di-pi-methane rearrangement is firmly established as a mode of synthesizing
      three-membered-ring compounds. We now report the tri-pi-methane counterpart.

PMID- 10930284
TI  - Tandem anionic 5-Exo dig cyclization/Claisen rearrangement as an efficient route
      to fused polycyclic ring systems.
AB  - The scope and limitations of a tandem 5-exo dig cyclization/Claisen rearrangement
      sequence involving appropriately substituted 4-alkyn-1-ols as an efficient "one
      pot" route to fused tricyclic ring systems is described. The reaction rates were
      found to be strongly dependent on the nature of the terminal substitutent of the
      triple bond. In some cases the entire sequence was found to proceed in good yield
      at temperatures as low as 115 degrees C.

PMID- 10930286
TI  - Preparation of titanated alkoxyallenes from 3-alkoxy-2-propyn-1-yl carbonates and
      (eta(2)-Propene)Ti(O-i-Pr)(2) as an efficient ester homoaldol equivalent
AB  - 3-Alkoxy-2-propyn-1-yl carbonates (2) react with a divalent titanium reagent
      (eta(2)-propene)Ti(O-i-Pr)(2) to afford titanated alkoxyallenes 1 which, in turn,
      react with aldehydes regiospecifically to provide the corresponding gamma
      addition products in good to excellent yields, thus affording a convenient method
      for synthesizing gamma-hydroxy esters 3 and/or gamma-butyrolactones 4.

PMID- 10930287
TI  - Catalyzed asymmetric diels-alder reaction of benzoquinone. Total synthesis of (-)
      ibogamine.
AB  - The Diels-Alder addition of diene 2 with benzoquinone catalyzed by (S)-BINOL
      TiCl(2) produced cycloadduct 5 in >65% yield and 87% ee. The cycloadduct was
      transformed into (-)-ibogamine in nine steps (10% overall yield from
      benzoquinone). A model for the transition state leading to 5 is proposed.

PMID- 10930288
TI  - Dynamic kinetic resolution of allylic alcohols mediated by ruthenium- and lipase
      based catalysts.
AB  - An enzyme-metal combo reaction has been developed for the dynamic kinetic
      resolution of allylic alcohols in which racemic substrates are transformed by a
      lipase and a ruthenium complex in the presence of an acyl donor to allylic
      acetates of high optical purity in over 80% yield.

PMID- 10930289
TI  - Chiral silylation reagents for the determination of absolute configuration by NMR
      spectroscopy.
AB  - We have investigated the use of chiral silylating reagents as analytical probes
      for determining the absolute stereochemistry of natural products by NMR
      spectroscopy. These reagents are prepared in high chemical yield in one step and
      can be used to derivatize chiral allylic alcohols which are incompatible with
      ester-based methodologies. Microscale ( approximately 400 nmol) derivatization
      conditions have been defined. The resulting siloxane diastereomers are readily
      distinguished by their (1)H NMR spectra.

PMID- 10930290
TI  - Suzuki cross-coupling reactions catalyzed by palladium nanoparticles in aqueous
      solution
AB  - Palladium nanoparticles stabilized by poly(N-vinyl-2-pyrrolidone) (PVP) are
      efficient catalysts for the Suzuki reactions in aqueous medium. The time
      dependence of the fluorescence intensity of the biphenyl product in the reaction
      between iodobenzene and phenylboronic acid is used to determine the initial rate
      of the catalytic reaction. The initial rate depends linearly on the concentration
      of Pd catalyst, suggesting that the catalytic reaction occurs on the surface of
      the Pd nanoparticles.

PMID- 10930291
TI  - Syntheses and stereochemical revision of pseudopterosin G-J aglycon and
      helioporin E.
AB  - Revised structures are proposed for pseudopterosin G-J aglycon and helioporin E.

PMID- 10930292
TI  - Stimulatory and inhibitory action of cytokines on the regulation of hCMV-IE
      promoter activity in human endothelial cells.
AB  - Viral promoters are commonly used as regulatory elements in gene therapy vectors
      due to their strong activity in various cell lines in vitro. However, transgene
      expression under the control of viral promoters in vivo has been shown to be
      limited to a short period of time. Several mechanisms for the transient
      expression of the delivered transgene may be important including deletion of
      transduced cells or promoter downregulation. Recently we reported that cytokines
      may either decrease or increase the activity of the human cytomegalovirus (hCMV)
      promoter in monocytes depending on the differentiation status of the transduced
      cells. For many applications, the gene of interest has to be delivered into an
      inflammatory milieu (tumour, ischaemia/reperfusion, vector-induced inflammation
      etc.). In this report we investigated the influence of various inflammatory
      cytokines on the hCMV-IE promoter activity in transduced human primary
      endothelial cells (Huvec) in vitro, which may be the first target cells after
      gene transfer into different organs. Cultured cells were infected with an E1
      deleted adenoviral vector encoding for E. colibeta-galactosidase (Adbeta-gal)
      driven by the hCMV-IE promoter and incubated either with or without various
      cytokines. Our results indicate that interferon-gamma (IFN-gamma) and interleukin
      10 (IL-10) downregulate promoter activity in endothelial cells whereas, in
      contrast, tumour necrosis factor (TNF-alpha), interleukin 1beta (IL-1beta) and
      interleukin 4 (IL-4) increased the promoter activity. These results suggest that
      inflammatory processes influence the in vivo expression of transferred viral
      promoter controlled genes of interest.

PMID- 10930293
TI  - Regulation of TNF-alpha expression in normal macrophages: the role of C/EBPbeta.
AB  - C/EBPbeta is present in monocytes and macrophages, binds to the proximal region
      of the TNF-alpha promoter, and contributes to its regulation. This study was
      performed to characterize the ability of C/EBPbeta to regulate the TNF-alpha gene
      in myelomonocytic cells and primary macrophages. In transient transfection
      assays, overexpression of wild type C/EBPbeta resulted in a 3-4-fold activation
      of a 120 base pair TNF-alpha promoter-reporter construct, while overexpression of
      a dominant negative (DN) C/EBPbeta inhibited LPS-induced activation. In vitro
      monocyte-differentiated macrophages, infected with an adenoviral vector
      expressing the DN C/EBPbeta (AdDNC/EBPbeta) or the control Adbetagal, expressed
      their transgenes weakly, however expression was greatly enhanced in the presence
      of PMA. Infection with AdDNC/EBPbeta resulted in 60% suppression of LPS induced
      TNFalpha secretion compared to Adbetagal infection (P<0.001) in PMA-treated
      macrophages. Northern blot analysis demonstrated approximately a 40% reduction of
      the TNF-alpha mRNA in the presence of the DN C/EBPbeta, suggesting that the
      effect of the DN C/EBPbeta was at the transcriptional level. In contrast,
      AdDNC/EBPbeta infection did not result in inhibition of LPS-induced TNF-alpha
      secretion in the absence of PMA. Further, DN versions of both C/EBPbeta and c
      Jun, but not NF-kappaB p65, suppressed PMA-induced TNF-alpha secretion in
      macrophages. These observations demonstrate that, C/EBPbeta and c-Jun contribute
      to the regulation of the TNF-alpha gene in normal macrophages following treatment
      with PMA.

PMID- 10930294
TI  - Differential glycosylation of two glycoproteins synthesized by murine B cells in
      response to IL-4 plus IL-5.
AB  - We sought to determine whether selected cytokines, known to stimulate profoundly
      B-cell activation and differentiation, also have as yet unrecognized effects upon
      the glycosylation of secreted Ig and/or membrane-associated proteins. The
      glycosylation of both secreted IgM and membrane-bound MHC Class-I synthesized by
      CH12LX cells was detected by enzyme-lectin conjugates in immunoabsorption assays.
      Stimulation of B cells with IL-4 plus IL-5 significantly decreases the terminal
      glycosylation of secreted IgM, whereas LPS has a minor effect, despite the fact
      that both stimuli are equipotent for IgM secretion. Neither LPS nor IL-4 plus IL
      5 affect MHC Class-I expression. However, IL-4 plus IL-5 substantially increases
      the terminal glycosylation of MHC Class-I produced from both mIgM(+)and
      mIgA(+)CH12LX cells. LPS has no or a modest effect on the terminal glycosylation
      of MHC Class-I produced from CH12LX cells. These results suggest that Th(2)
      derived cytokines differentially influence the glycosylation of secreted and
      membrane-associated glycoproteins of B cells. In turn, this might elucidate the
      basis of aberrant glycosylation reported in conditions such as IgA nephropathy,
      cancer and rheumatoid arthritis.

PMID- 10930295
TI  - Secretory and cytosolic phospholipase A(2)regulate the long-term cytokine-induced
      eicosanoid production in human keratinocytes.
AB  - The involvement of cytosolic phospholipase A(2)(cPLA(2)) and secretory non
      pancreatic PLA(2)(npPLA(2)) in release of arachidonic acid (AA) preceding
      eicosanoid formation in the human keratinocyte cell line HaCaT was examined.
      Interleukin 1beta (IL-1beta) and tumour necrosis factor-alpha (TNF), phorbol
      myristate acetate (PMA) and calcium ionophore A(23187)increased the extracellular
      AA release, and stimulated eicosanoid synthesis as determined by HPLC analysis.
      The main metabolites after stimulation with IL-1beta, PMA or A(23187)were PGE(2),
      an unidentified PG and LTB(4), while TNF stimulated HETE-production. Both
      cPLA(2)and npPLA(2)message and enzyme activity were detected in unstimulated
      HaCaT cells. IL-1beta, PMA and TNF increased both cPLA(2)enzyme activity and
      expression, but did not lead to any increase in npPLA(2)expression or activity.
      The selective npPLA(2)inhibitors LY311727 and 12-epi-scalaradial, or the
      cPLA(2)inhibitor arachidonyl trifluoro methyl ketone (AACOCF(3)) reduced IL-1beta
      induced eicosanoid production in a concentration dependent manner. The results
      presented strongly suggest that both cPLA(2)and npPLA(2)contribute to the long
      term generation of AA preceding eicosanoid production in differentiated, human
      keratinocytes. Inhibitors against npPLA2 or cPLA2 enzymes should be useful in
      treating inflammatory skin diseases, such as psoriasis.

PMID- 10930296
TI  - Quiescence of CD34-negative haematopoietic stem cells is mediated by
      downregulation of Cyclin B and no stat activation.
AB  - The CD34-negative, adherent growing, fibroblast-like canine haematopoietic stem
      cell line D064 was recently identified as the earliest progenitor population in
      the bone marrow. D064 cells are predominately quiescent. Quiescence is mediated
      by the accumulation of the cyclin-dependent kinase inhibitor p27(kip-1)and in
      parallel, by the downregulation of Cyclin B, leading to an accumulation of
      quiescent cells in the G(0)/G(1)-phase of the cell cycle. Stem cell factor (SCF),
      the ligand for the tyrosine kinase receptor c-kit, usually induces
      differentiation of the CD34-negative stem cells into CD34-positive haematopoietic
      precursors. SCF also suppresses the expression of c-myc-dependent Cyclin E, which
      is not transcribed initially, but expression occurs later on. Interleukin 6 (IL
      6) instead rather promotes proliferation, but fails to induce proliferation in
      the majority of CD34-negative stem cells due to no STAT activation in quiescent
      cells. Nevertheless, the potential of quiescent D064 cells to proliferate
      eventually, becomes apparent by the low-level expression of IL-6 dependent STAT
      factors. D064 cells also spontaneously start to express Bax, while Bcl-2 is
      downregulated in parallel. In summary, CD34-negative haematopoietic stem cells
      dwell in the marrow or other niches as quiescent cells, until they can respond to
      autocrine or paracrine growth factor-mediated signals.

PMID- 10930297
TI  - Lps induces IL-6 in the brain and in serum largely through TNF production.
AB  - We investigated the relative contribution of IL-6 and PGE2 directly induced by
      LPS and indirectly induced via TNF, using in vivo and in vitro models in the
      mouse. In these models we have used as tools an anti-TNF antibody and a
      cyclooxygenase inhibitor, the S enantiomer of ketoprofen (S-KPF). Anti-TNF
      antibodies inhibited LPS-induced IL-6 production in three different models: IL-6
      production by mouse peritoneal macrophages in vitro; serum IL-6 levels induced by
      intraperitoneal LPS; and brain IL-6 levels induced by an intracerebroventricular
      injection of LPS. However, in vitro anti-TNF antibodies, did not inhibit LPS
      induced PGE2, indicating that this effect is not mediated by TNF. Since PGE2 has
      an opposite effect on TNF and IL-6 production, inhibiting that of TNF but
      inducing that of IL-6, we investigated the effect of S-KPF on TNF and IL-6
      production in vivo following LPS injection. Both TNF and IL-6 induction was
      augmented by S-KPF, but anti-TNF antibodies abolished the augmentation of IL-6
      production. Thus, the effect of anti-inflammatory drugs on IL-6 production in
      some models can be secondary to their effect on TNF production.

PMID- 10930298
TI  - The production and biological assessment of cervine interferon gamma.
AB  - Cervine interferon gamma (IFN-gamma) was cloned and expressed using an
      Escherichia coli expression system pET-32. The expressed protein contained a 6
      histidine purification tag and an 11 kDa thioredoxin fusion partner 5' to the IFN
      gamma molecule. The ability of IFN-gamma to inhibit the killing of Madin-Darby
      bovine kidney cells by Semliki forest virus was used as a measure of the
      bioactivity of the recombinant cervine IFN-gamma (rIFN-gamma). It was shown that
      the presence of the thioredoxin fusion partner 5' to the IFN-gamma molecule did
      not affect its biological activity. As in the mouse model, it was shown that
      cervine rIFN-gamma was able to down-regulate the transcription of interleukin 10
      mRNA while up-regulating the transcription of interleukin 12 mRNA in
      lipopolysaccharide-sensitized, peripheral blood mononuclear cells. A prototype
      ELISA was tested for its ability to detect both recombinant and native IFN-gamma.
      The ELISA was able to detect rIFN-gamma at concentrations greater than 100 pg/ml.
      It was also used to detect native IFN-gamma produced by peripheral blood
      lymphocytes from Mycobacterium bovis infected or vaccinated deer after in vitro
      restimulation with antigen. The rIFN-gamma and the cervine IFN-gamma specific
      ELISA provide valuable tools with which to study important zoonotic infections in
      farmed and wild deer.

PMID- 10930299
TI  - IL-12 elispot assays to detect and enumerate IL-12 secreting cells.
AB  - The cytokine IL-12 promotes Th(1)type immune responses and plays a key role in
      immune regulation. The complex nature of IL-12 hampered its detection without use
      of stimulants that might give less relevant information. To detect circulating IL
      12 p40, we developed enzyme-linked immunospot (ELISPOT) assays that allow
      enumeration of IL-12 p40 secreting cells without prior in vitro stimulation of
      the cells. In parallel, intracellular staining of IL-12 p40 by flow cytometry was
      performed to compare the two methods. IL-12 p40 secreting cells were detected in
      healthy subjects at a mean number of 103+/-155 per 10(5)blood mononuclear cells
      (MNC). Numbers of IL-12 p40 secreting blood MNC correlated with IL-12 p40
      positive blood MNC detected by flow cytometry. Bacterial endotoxins and the
      inflammatory cytokines TNF-alpha and IFN-gamma control IL-12 production by
      antigen presenting cells. Utilizing IL-12 p40 ELISPOT assays, we could confirm
      occurrence of elevated numbers of IL-12 p40 secreting blood MNC after stimulation
      with TNF-alpha, IFN-gamma, LPS, LPS+TNF-alpha or LPS+IFN-gamma, compared to
      cultures without stimulant. Due to its central role in inflammation and
      autoimmunity, IL-12 is an attractive target for immunotherapy. IL-12 p40 ELISPOT
      assays represent a sensitive, specific and reliable tool for investigating the
      role of IL-12 in both health and disease.

PMID- 10930300
TI  - Changes of cytokines during the course of graft-versus-host disease following
      bone marrow transplantation: a case report.
AB  - Allogeneic bone marrow transplantation was performed in a 24-year-old woman with
      acute myelogenous leukemia in the first remission (FAB classification: M4). Graft
      versus-host disease occurred from around day 150 after bone marrow
      transplantation. The levels of tumour necrosis factor-alpha, interleukin 12, and
      intercellular adhesion molecule-1 were elevated in the early stage of graft
      versus-host disease, followed by elevation of interleukin 10 and interleukin 8.
      Her symptoms subsequently improved and all of these parameters became normal. The
      levels of thrombomodulin and plasminogen activator inhibitor type 1 showed
      changes that were in parallel with the clinical course. Interleukin 1beta,
      interleukin 6, interleukin 2, and interferon-gamma showed no changes throughout
      the course of her graft-versus-host disease. These findings suggested the
      possibility that release of inflammatory molecules occurred at the onset of graft
      versus-host disease and caused vascular endothelial damage, which led to the
      exacerbation of her disease.

PMID- 10930301
TI  - IL-10 and IL-12 are the main regulatory cytokines in visceral leishmaniasis.
AB  - Visceral leishmaniasis (VL) is characterized by the absence of cytokines such as
      IFN-gamma and IL-12. Cure of VL is associated with a restoration of the ability
      to make these cytokines. The aim of the present study was to evaluate the role of
      IL-12 in the recovery of the ability to produce IFN-gamma and to test whether or
      not IL-4 IL-10 and/or TGF-beta could suppress IFN-gamma production by PBMC from
      treated VL patients. High stimulation index (SI) of proliferation was observed in
      PBMC from subjects stimulated with Leishmania chagasi antigen (181+/-83).
      Neutralizing IL-12 inhibited lymphoproliferation [stimulation index (SI) of 210+/
      114 to 1+/-0.6 (P<0.01)] and/or the production of IFN-gamma [2792+/-402 pg/ml to
      407+/-449 pg/ml (P<0.01)]. Recombinant IL-10 abrogated the lymphoproliferation
      (SI=2+/-3) while recombinant IL-4 or TGF-beta had no effect on this response
      (147+/-22 and 194+/-12 respectively). IFN-gamma was high when PBMCs were
      stimulated with L. chagasi (873+/-400 pg/ml) and this was abrogated by the
      addition of IL-10 (5+/-2 pg/ml). In contrast neither IL-4 or TGF-beta suppressed
      IFN-gamma production (837+/-244 pg/ml and 759+/-523 pg/ml). These results
      indicate that IL-12 plays an important role in the ability of treated VL patients
      to make IFN-gamma and that IL-10 but not IL-4 or TGF-beta inhibits this response.

PMID- 10930302
TI  - Identification of polymorphisms within the vascular endothelial growth factor
      (VEGF) gene: correlation with variation in VEGF protein production.
AB  - Dysregulated vascular endothelial growth factor (VEGF) expression has been
      implicated as a major contributor to the development of a number of common
      disease pathologies. The aim of this study was to establish the extent of genetic
      variability within the VEGF gene and to determine whether this genetic variation
      influenced levels of VEGF protein expression. The promoter region and exon 1 of
      the VEGF gene were screened for polymorphisms using single-stranded conformation
      (SSCP) polymorphism analysis and direct PCR-sequencing. We identified 15 novel
      sequence polymorphisms most of which were rare. Eleven of these polymorphisms
      were single base substitutions, three were single base insertions and one was a
      two base deletion. Thirteen of the polymorphisms were located within the promoter
      and two in the 5' untranslated region (5'UTR) of the gene. We established PCR
      RFLP typing systems for ten of the polymorphisms. For the two common
      polymorphisms at -460 and +405, we developed a combined sequence specific priming
      (SSP) PCR typing system to determine the cis/trans orientation of each allele and
      hence, ascertain haplotypes. A significant correlation was observed between
      lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cell (PBMC) VEGF
      protein production and genotype for the +405 polymorphism.

PMID- 10930303
TI  - Multiple regulation of constitutive and induced interleukin 8 secretion in human
      myelomonocytic cell lines.
AB  - Secretion of interleukin 8 (IL-8) and its regulation was investigated in
      myelomonocytic leukaemia cell lines. Quantification by ELISA revealed a
      constitutive production in the cell lines HL-60, ML-2, MONO-MAC-6 and MUTZ-3
      ranging between 1500 and ca. 5000 pg/ml IL-8 per million cells. No measurable IL
      8 was detected in the culture medium of MONO-MAC-1 and THP-1. Stimulation with
      lipopolysaccharide (LPS) or tetradecanoyl phorbol acetate (TPA) significantly
      increased the IL-8 level secreted by all cell lines; the best producers were TPA
      treated MONO-MAC-6 and MUTZ-3 cultures, generating more than 50 000 pg/ml IL-8.
      Also the calcium ionophore A-23187, IL-13, macrophage colony-stimulating factor
      (M-CSF), thapsigargin, an inhibitor of the Ca(2+)-ATPase, and tumour necrosis
      factor-alpha (TNF-alpha) strongly enhanced the IL-8 production in MONO-MAC-6
      cells. The glucocorticoid dexamethasone and the protein kinase inhibitor
      staurosporine distinctively inhibited the IL-8 production of MONO-MAC-6 cells.
      Thus, our results demonstrate a strong constitutive IL-8 secretion in human
      myelomonocytic leukaemia cell lines; the variety of different modulators
      affecting IL-8 production leads to the suggestion of a multiple regulation of IL
      8 expression and secretion.

PMID- 10930304
TI  - Interleukin 2-induced antinociception partially coupled with mu receptor.
AB  - The present study was designed to investigate the involvement of mu receptor in
      interleukin 2-induced antinociception. Intraplantar injection of human
      recombinant interleukin 2 (rIL-2) (1. 5x10(4) U) significantly enhanced pain
      threshold as measured by paw withdrawal latencies (PWLs) to noxious radiant heat
      in normal rats. After administration of rIL-2, PWLs were also markedly increased
      in morphine-tolerant and chronic constriction injury (CCI)-operated rats, which
      have been proven morphine-insensitive. rIL-2-induced antinociception in both
      morphine-tolerant and CCI-operated rats was significantly lower than that in
      normal rats. rIL-2 antinociception was partially blocked by naloxone (1 mg/kg
      i.p.) in normal rats but remained unchanged in the CCI group. Our results suggest
      that the use of rIL-2 in human medical practice may be extended for its
      effectiveness in relief of neuropathic pain induced by CCI. Here we infer that mu
      receptor plays an critical role in IL-2-induced antinociception and that there
      are also some other receptors involved in this process.

PMID- 10930305
TI  - Cytokine and free radical responses of alveolar macrophages in vitro to asbestos
      fibres.
AB  - A method for culturing primary rat alveolar macrophages (AMs) for 14 days was
      used to compare their responses to crocidolite and chrysotile asbestos fibres.
      Exposure to crocidolite increased production of tumour necrosis factor-alpha (TNF
      alpha) and interleukin 1beta (IL-1beta), whereas exposure to chrysotile did not;
      neither fibre altered the production of interleukin 6 (IL-6). IL-1beta production
      increased progressively, while TNF-alpha was fully elevated from day 1.
      Conversely, chrysotile, but not crocidolite, increased production of superoxide
      anion and nitric oxide (NO) radicals. These differential responses were only
      observed by extending the culture beyond the usual 1-3 days.

PMID- 10930306
TI  - Role of haemodialysis and hepatitis c virus infection in spontaneous and induced
      cytokine production of patients with chronic renal disease.
AB  - Cytokines modulate general and virus infection-related host immune responses. We
      have investigated cytokine responses in chronic renal disease patients with
      regard to haemodialysis and hepatitis C virus (HCV) infection. Compared with
      healthy subjects with normal renal function (n=15), non-dialyzed/renal disease
      individuals without HCV infection (n=11) showed increased production of tumour
      necrosis factor (TNF)-alpha, interleukin (IL-)6, IL-10, interferon (IFN-)gamma
      and IL-12 by blood mononuclear cells (P<0.05). These inflammatory cytokine
      responses were abolished in haemodialysis patients (n=37;P<0.05), except for IL
      12. This hyporesponsiveness in haemodialysis patients was more evident in
      stimulatory conditions, as shown by the consistent inhibition of IFN-gamma
      production, and the failure of exogenous IFN-gamma to prime for IL-12
      inducibility (P<0.01). The disturbed cytokine response appeared to focus in the T
      helper lymphocyte phenotype 1 (Th(1)) because the stimulation of IL-6 and IL-10
      (Th(2)phenotype cytokines) was not impaired. The pattern of response was similar
      among haemodialysis patients with (n=24) or without (n=13) HCV infection.
      However, HCV-positive haemodialysis patients had a blunted TNF-alpha response
      (P<0.05) and failed to increase the stimulated IFN-gamma and IL-12 production
      (P<0.01) compared with chronic hepatitis C patients without renal disease (n=25).
      On the contrary, IL-10 stimulation was higher in HCV-positive haemodialysis
      patients (P<0.01). These results disclose the presence in haemodialysis patients
      of markedly abnormal general and HCV infection-related cytokine responses; the
      inhibitory alterations appear to affect predominantly the stimulated responses
      via the Th(1)subset and its relationship with monocyte response with possible
      pathogenic and therapeutic implications.

PMID- 10930307
TI  - Induction of angiotensin-converting enzyme by oncostatin m in human endothelial
      cells.
AB  - OBJECTIVE: To examine the role of oncostatin M (OSM) in the regulation of
      angiotensin converting enzyme (ACE) in endothelial cells. METHODS: Cultured
      endothelial cells were incubated with OSM (25-200 pM) for 24 h. Incubations were
      performed without or with the tyrosine kinase inhibitor, herbimycin (87 nM), or
      the selective MAP kinase kinase inhibitor, PD98059 (50 microM). ACE amount in
      intact endothelial cells was measured by an inhibitor binding assay and ACE mRNA
      levels by RNase protection assay. RESULTS: OSM caused a dose dependent increase
      in ACE amount and increased the expression of ACE mRNA. The stimulatory effect of
      OSM was inhibited by pretreatments with herbimycin or PD98059. CONCLUSIONS: OSM
      induced ACE in cultured HUVECs. Tyrosine kinase and MAPK activation were probably
      involved in ACE induction. Local induction of ACE by OSM in the vascular wall may
      be a consequence of inflammatory processes leading to locally increased
      production of angiotensin II and breakdown of bradykinin.

PMID- 10930309
TI  - Tumour necrosis factor-alpha expression in idiopathic dilated cardiomyopathy:
      correlation to myocardial inflammatory activity.
AB  - High numbers of inflammatory cells are found in a subgroup of patients with
      idiopathic dilated cardiomyopathy (IDCM). We hypothesized that the extent of
      inflammation is linked to myocardial TNF-alpha expression in human IDCM. Fourteen
      patients who consecutively underwent endomyocardial biopsy (EMB) were stratified
      into two groups-a group with low and a group with high myocardial inflammatory
      index (MII)-based on immunohistochemical analysis of cellular infiltration and
      HLA I and II expression. Myocardial TNF-alpha messenger RNA (mRNA) expression was
      determined by reverse transcriptase polymerase chain reaction, TNF-alpha protein
      was localized by immunohistochemistry and TNF-alpha serum levels were measured by
      EIA. IDCM patients with a high MII (n=6) showed a 1. 9-fold higher TNF-alpha mRNA
      expression when compared to IDCM patients with low MII (n=8, P=0.020). TNF-alpha
      protein was detected at perinuclear regions of cardiac myocytes and the
      endothelium. TNF-alpha serum levels were 3.0 (0.55) pg/ml in patients with high
      MII compared to 1.35 (0.20) pg/ml in patients with low MII (P=0.017). According
      to immunolocalization cardiac myocytes and the endothelium seem to be the major
      source of TNF-alpha production. Whether the elevated systemic level of TNF-alpha
      found in patients with high MII are elaborated by the myocardium or are produced
      by other tissues representing a general immune activation is not clear.

PMID- 10930308
TI  - Nuclear factor-kappa b activation in silica-induced interleukin 8 production by
      human bronchial epithelial cells.
AB  - Recent studies indicate that interleukin 8 (IL-8) plays an important role in
      interstitial lung diseases including silica-induced lung inflammation. To
      investigate the regulation of IL-8 expression and production in human bronchial
      epithelial cells, we examined the effects of silica on NF-kappaB activation.
      Human bronchial epithelial cell line BET-1A was cultured with hormonally defined
      Ham's F12 medium. The administration of silica induced IL-8 production in BET-1A
      dose-dependently and time-dependently. Northern blot analysis demonstrated that
      silica upregulated IL-8 expression in BET-1A. Moreover, electrophoretic mobility
      shift assays revealed that NF-kappaB activation occurred in the presence of
      silica, which was inhibited by antioxidants such as N-acetylcysteine (NAC). These
      data suggest that reactive oxygen species may be involved in the activation of NF
      kappaB induced by silica.

PMID- 10930310
TI  - Weaning induces an increase in the number of specific cytokine-secreting
      intestinal lymphocytes in mice.
AB  - Intestinal immunity differs from systemic immunity in several aspects and is
      frequently studied separately. In this work we have analysed the frequency of
      mononuclear cells spontaneously secreting the cytokines IL-2, IL-4, IL-5, IL-6,
      IL-10, interferon gamma (IFN-gamma) and tumour necrosis factor (TNF-alpha), in
      Peyer's patches and lamina propria of small intestine in mice by enzyme linked
      immunosorbent spot (ELISPOT) during 1 month after weaning. We have found a high
      percentage of spontaneous Th(1)as well as Th(2)cytokine-secreting lymphocytes in
      both populations, Peyer's patches and lamina propria. An increase in the number
      of the lymphocytes secreting most of the studied cytokines, at 1 and 2 weeks
      after weaning, was also observed. These results suggest that the increase in the
      number of cytokine secreting lymphocytes may be one of the potential mechanisms
      involved in the development of the intestinal immune system at weaning.

PMID- 10930311
TI  - Platelet-derived growth factor (PDGF)-AA: a self-imposed cytokine in the
      proliferation of human fetal osteoblasts.
AB  - PDGF, a multiple mitogen, stimulates osteoblast replication and bone collagen
      degradation, and it has been described as a key factor in bone metabolism.
      Recently, PDGF was disclosed to be the autocrine cytokine of human osteoblasts.
      PDGF's effect on human bone development needs elucidation, and the mechanism of
      PDGF-AA autocrining remains unclear. In this work, osteoblasts were isolated from
      human fetal calvaria which resemble the cells in developing bone tissue. Using an
      in vitro model, the effect of PDGF-AA on the cells was investigated with the
      results showing that (i) after PDGF-AA was added into the medium for 24 h, PCI of
      the cells increased by 48.2% (P<0.05), and PCI decreased after the removal of
      PDGF-AA. (ii) 24 h after treatment with PDGF-AA, the percentage of osteoblasts in
      G(0)/G(1)phase decreased and that in S phase increased. (iii) The expression of
      PDGF-A mRNA was upregulated by PDGF-AA, PDGF-BB, TGFbeta,and bFGF respectively.
      These results proved that: (i) PDGF-AA enhances cell replication by accelerating
      cell recycle and inducing the quiescent cells into the proliferation portion of
      cell cycle. (ii) PDGF-AA is a self-imposed cytokine in human fetal osteoblast
      replication.

PMID- 10930312
TI  - IL-6 protein production by airway epithelial(-like) cells disabled in IL-6 mRNA
      degradation.
AB  - IL-6 mRNA and protein expression in human airway epithelial-like H292 cells
      depends on rapid, but regulable IL-6 mRNA degradation. We restricted IL-6 mRNA
      degradation by partially inhibiting protein synthesis and studied the IL-6
      response. Despite partial inhibition of protein synthesis, IL-6 protein
      production was increased and prolonged. Furthermore, the threshold concentration
      for stimuli of IL-6 protein production decreased and the dose-response curves
      became steeper. Similar findings were obtained with primary human bronchial
      epithelial cells. This exaggerated production may apply to other proteins encoded
      by labile mRNA and is likely to occur during viral infection of airway epithelial
      cells.

PMID- 10930313
TI  - Interleukin secretion, proteoglycan and procollagen alpha(1)(I) gene expression
      in Crouzon fibroblasts treated with basic fibroblast growth factor.
AB  - The present study provides the first evidence that fibroblasts obtained from
      patients affected by Crouzon syndrome, a rare craniosynostosis, despite mutations
      in the high-affinity bFGF receptor retain their capacity to respond to bFGF. The
      growth factor reduces IL-1 secretion, downregulates biglycan and procollagen
      alpha(1)(I), and increases betaglycan expression. Since betaglycan is a co
      receptor for bFGF signalling, an alternative signal transduction pathway is
      suggested in Crouzon fibroblasts, to explain the documented changes in ECM
      macromolecule production.

PMID- 10930314
TI  - Lens culinaris, Phaseolus vulgaris and vicia faba lectins specifically trigger IL
      8 production by the human colon carcinoma cell line CACO-2.
AB  - Cultured Caco-2 cells were stimulated with Lens culinaris, Phaseolus
      vulgarisandVicia fabalectins. The production of IL-1, IL-6, IL-8 and MCP-1 was
      measured by ELISA and RT-PCR. IL-8 production appeared to be specifically
      triggered upon stimulation with all three lectins used, since none of the other
      cytokines tested were produced. The IL-8 secreted may induce the extravasation of
      activated neutrophils and generate tissue damage. A similar mechanism may be
      implicated in the lesions observed after infection by some enteric pathogens,
      with lectin-like domains on their membrane. Finally, this model may be suitable
      one to study the regulation of IL-8 production.

PMID- 10930315
TI  - Synthesis of interleukin 1beta and interleukin 6 by stimulated rat peritoneal
      macrophages: modulation by glutamine.
AB  - Synthesis and secretion of IL-1beta and IL-6 were compared in LPS-stimulated rat
      peritoneal macrophages, and the effect of glutamine studied. LPS induced a
      parallel increase in mRNA and synthesis of IL-1beta and IL-6. IL-1beta
      accumulated mainly in the cytosol and IL-6 in the culture medium. Glutamine
      addition increased the synthesis of both cytokines, but the overall production
      (intra-+extracellular) of IL-1beta increased two-fold, although that of IL-6
      increased only 1.3-fold. The influence of glutamine is discussed.

PMID- 10930316
TI  - Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and
      immunological responses in interferon gamma deficient mice.
AB  - Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune
      disease induced by immunization with uveitogenic retinal antigens, or by the
      adoptive transfer of uveitogenic T-cells of the Th-1-like phenotype. We have
      previously shown that IFN-gamma-deficient mice (GKO) on the C57BL/6 background
      are equally susceptible to interphotoreceptor retinoid binding protein (IRBP)
      induced EAU as the wild type (WT). In the present study, we evaluated EAU
      induction in GKO mice by the newly described H-2(b)epitope contained in residues
      1-20 of human IRBP, and compared it to the response to the whole IRBP molecule.
      Similarly to previous observations with IRBP-induced EAU, delayed type
      hypersensitivity (DTH) and lymphocyte proliferation responses were elevated in
      GKO mice, as was production of IL-5 and TNF-alpha. However, unlike the responses
      induced by whole IRBP, there was no detectable IL-10 production to the peptide.
      Histopathology on day 21 after immunization, revealed that both GKO and WT mice
      developed retinal lesions, including damage to the photoreceptor cell layer,
      vasculitis and inflammatory cellular infiltration, but disease scores were
      significantly higher in GKO, and retinal detachment was observed only in GKO
      mice. In contrast to the wild type, the cellular infiltrate in eyes of GKO mice
      contained a prominent component of eosinophils, although of lower proportion in
      peptide-induced than in IRBP-induced EAU. We conclude that the cytokine and
      inflammatory responses to human peptide 1-20 differ perceptibly from the
      responses to whole bovine IRBP, and may explain the elevated EAU scores of GKO
      mice compared to wild type.

PMID- 10930317
TI  - Analysis and quantitation of mRNAs encoding the alpha- and beta-subunits of rod
      photoreceptor cGMP phosphodiesterase in neonatal retinal degeneration (rd) mouse
      retinas.
AB  - The retinal degeneration(rd) mouse is a commonly-studied animal model of the
      family of human-inherited retinal blindness known as retinitis pigmentosa, and is
      a likely model in which therapies for these conditions will continue to be
      developed and tested. Mutation of the beta-subunit of the rod photoreceptor cell
      specific cyclic GMP phosphodiesterase is known to cause photoreceptor apoptosis
      in these mice. However, the molecular phenotype of this mutation in terms of
      quantitative levels of the phosphodiesterase alpha- and beta-subunit messenger
      RNAs remains unknown. In this study, the expression of the alpha- and beta
      phosphodiesterase subunits is compared in C57BL/6J +/+, rd /+, and rd / rd mouse
      retinas. Using the techniques of quantitative reverse transcription polymerase
      chain reaction and quantitative in situ hybridization, the expression of the
      subunit mRNAs was measured in retinas of postnatal mice 0-14 days of age.
      Additionally, full length coding sequences were amplified for both subunits, and
      the beta-phosphodiesterase subunit mRNA was further evaluated for evidence of
      alternative splicing. Lastly, a relative decrease in expression of the mutant
      beta-phosphodiesterase allele in rd /+ mice was observed.

PMID- 10930318
TI  - Distribution of growth factors and immune cells are altered in the lacrimal gland
      during pregnancy and lactation.
AB  - We have undertaken a series of studies to elucidate the roles of growth factors
      (FGF-2, EGF, TGF-beta1) and prolactin (PRL) in lacrimal gland function during
      pregnancy and lactation, and to better understand the status of the immune system
      within the lacrimal gland during those physiological states. In this initial
      study, lacrimal glands of pregnant (d15, d29), lactating (9d, 22d), and adult
      female control rabbits, were evaluated by immunohistochemistry, Western blotting
      and image analysis. In control rabbits EGF, TGF-beta1, and PRL, were
      immunolocalized primarily in the apical cytoplasm of intralobular ductal
      epithelial cells, and acini demonstrated a basement membrane-associated
      immunopositivity for TGF-beta1. FGF-2 immunolocalized in myoepithelial cells in
      the basal ductal epithelium and complexed to the basement membrane enclosing
      ducts and acini. Cells immunopositive for immune cell markers (RTLA and CD18)
      were apparent primarily around interlobular ducts. In d29 pregnant rabbits
      immunopositivity for EGF and TGF-beta1 was increased within intralobular ducts,
      both apically and basally, and within some interlobular ductal epithelial cells.
      Immunopositivity for PRL was strongest in d29 pregnant rabbits within the apical
      and basal cytoplasm of intralobular ductal epithelial cells. Immunopositivity for
      FGF-2 in myoepithelial cells was strong in d15 and d29 pregnant rabbits, although
      basement membrane-associated immunopositivity around acini was often decreased.
      Immunostaining for EGF and TGF-beta1 in lactating rabbits was similar to that in
      d29 pregnant rabbits, although basement membrane-associated immunopositivity
      around acini was more comparable to controls. By 22d lactation immunopositivity
      for FGF-2 closely resembled that in controls. Image analysis of pregnant and
      lactating rabbits demonstrated that cells immunopositive for RTLA and CD18 were
      less abundant around ducts and more abundant between acini, although in 22d
      lactating rabbits the size of periductal foci was increased to nearly that of
      controls. Western blots correlated well with the immunohistochemistry. Our
      findings demonstrate that pregnancy and lactation are accompanied by a shift in
      the distributions of growth factors and PRL, suggestive of increased release both
      apically into the lacrimal fluid and basally into the interstitium. Additional
      shifts in the distributions of cells of the immune system from periductal foci to
      interacinar sites suggest that there is a recruitment of immune cells away from
      ducts and toward the connective tissue interstitium surrounding the acini,
      possibly as part of a heightened state of immune readiness during pregnancy and
      lactation.

PMID- 10930319
TI  - Vascular remnants in the rabbit vitreous body. I. Morphological characteristics
      and relationship to vitreous embryonic development.
AB  - Using light and transmission electron microscopy, we observed novel structures in
      the rabbit vitreous body. They were found in 18 out of 27 eyes from rabbits 0.5
      36 months of age. These structures are scattered throughout the entire vitreous
      matrix. By light and transmission electron microscopy, they appear to be made up
      of the same structural components. Based upon their morphological appearance,
      they can be subdivided into two groups which we provisionally named 'intravitreal
      structure type 1 and 2' or 'IVS-1' and 'IVS-2'. IVS-1 has a highly variable
      morphology (e.g. star-shaped, round, oval), whereas IVS-2 is tubular. The
      dimensions of IVS-1 vary in relation to the mesh diameters of the collagen
      matrix, while those of IVS-2 do not. In adult rabbit eyes, we observed
      transitions between IVS-1 and intravitreal ghost vessels (acellular remnants of
      blood vessels), and between IVS-1 and IVS-2. In very young rabbits (14 days) we
      observed intravitreal ghost vessels consisting of tightly-packed IVS-1.
      Therefore, we concluded that IVS-1 and 2 are related structures presumably of
      vascular origin. It appears that they represent fragmented and non-fragmented
      acellular remnants of hyaloid blood vessels. The presence of vascular remnants
      throughout the entire vitreous matrix of adult rabbit eyes is in conflict with
      existing theories on the embryonic development of the vitreous body, which
      describe a strict spatial separation between the primary (vascular) and secondary
      (avascular) vitreous. However, it strongly supports an alternative theory that
      explains the formation of the secondary vitreous by a process of continuous
      remodelling of the primary vitreous.

PMID- 10930320
TI  - Vascular remnants in the rabbit vitreous body. II. Enzyme digestion and
      immunohistochemical studies.
AB  - The purpose of this study was to evaluate the composition of ghost vessels and
      the newly identified intravitreal structures type 1 and 2 (IVS-1 and 2) observed
      in the rabbit vitreous body. Rabbit eyes (n = 10, 0.5- approximately 36 months of
      age) were fixed and embedded in plastic. Post-embedding immuno transmission
      electron microscopy and enzyme digestion methods specifically directed at
      vascular extracellular matrix components (collagen IV, elastin and hyaluronan)
      were used in order to confirm the postulated vascular origin of IVS-1 and 2. In
      addition, markers of vitreous extracellular matrix components (collagen II,
      hyaluronan) were used. The postulated vascular nature of ghost vessels and IVS-1
      was confirmed by a positive labelling with anti-collagen IV, whereas the
      demonstration of elastin (by anti-elastin antibodies and elastase digestion) in
      IVS-1 and 2 confirms their arterial origin. These vascular remnants were also
      labelled with a hyaluronan marker and with anti-collagen II. The presence of
      remnants of the hyaloid artery system throughout the vitreous matrix is in
      conflict with a strict spatial separation between the primary and secondary
      vitreous during embryonic development as proposed in the literature. It strongly
      supports an alternative theory which suggests an interactive remodelling of this
      matrix. The presence of hyaluronan in remnants of the hyaloid system is
      inconclusive, since hyaluronan is a component both of the adult vitreous matrix
      and of the vascular extracellular matrix. The presence of collagen II in vascular
      structures is highly interesting, since it supports another challenging theory,
      which suggests that lamellae develop alongside tracts formerly occupied by the
      larger hyaloid vessels.

PMID- 10930321
TI  - Effect of oral losartan potassium administration on intraocular pressure in
      normotensive and glaucomatous human subjects.
AB  - The effects of the type 1 angiotensin II receptor antagonist Losartan potassium
      on intraocular pressure (IOP) were studied. Four groups of subjects were
      analysed: group A, ten controls; group B, ten patients with essential arterial
      hypertension and with IOP within the normal range; group C, ten patients with
      primary open angle glaucoma (POAG), but without essential arterial hypertension;
      group D, ten patients with arterial hypertension and POAG. The study design was
      held in a randomized crossover double-blind fashion. Systolic and diastolic
      arterial pressure, heart rate, pupil diameter, IOP and total outflow facility
      were recorded at baseline and at 1 hr intervals up to 6 hr, following the oral
      administration of 50 mg of Losartan potassium and/or placebo. The alternative
      treatment was given a week later. Drug administration significantly reduced IOP
      in all subjects. No variation in heart rate and pupil diameter was observed
      during the follow-up period. Blood pressure dropped only in arterial hypertensive
      patients (groups B and D). Total outflow facility increased significantly in all
      groups. Placebo did not induce any variation in all groups. These findings
      demonstrate that the mechanism by which Losartan potassium reduces intraocular
      pressure is not mediated by a decrease in blood pressure, but rather it is more
      specific, confirming the role of the renin-angiotensin system also in the
      regulation of intraocular pressure in man.

PMID- 10930322
TI  - Evaluation of the myosin VIIA gene and visual function in patients with Usher
      syndrome type I.
AB  - Usher syndrome type I (USH1) is a recessively-inherited disorder consisting of
      retinitis pigmentosa, profound congenital deafness, and vestibular ataxia. It can
      be caused by mutations in at least six different loci (USH1A-1F). The gene
      encoding human myosin VIIA (MYO7A) is the USH1B locus. In this study, 66
      unrelated patients with USH1 were evaluated for defects in MYO7A using single
      strand conformation polymorphism analysis and direct genomic sequencing. Twenty
      nine per cent of cases were found to have likely pathogenic MYO7A mutations. A
      total of 22 likely pathogenic changes were identified, 18 of which were novel.
      Cosegregation analysis of mutations in five available families showed that the
      MYO7A changes segregated with the disease in an autosomal recessive fashion.
      Average visual function as measured by visual acuity, visual field area, and ERG
      amplitude was not significantly different between the group of patients with
      likely pathogenic MYO7A changes and the group in which no likely pathogenic MYO7A
      changes were detected.

PMID- 10930323
TI  - Investigation of the mechanism of action of microperoxidase-11, (MP11), a
      potential anti-cataract agent, with hydrogen peroxide and ascorbate.
AB  - The interaction of hydrogen peroxide, ascorbate and microperoxidase-11 (MP11), a
      ferriheme undecapeptide derived from cytochrome c, has been investigated using
      spectrophotometry, oxymetry, electron paramagnetic resonance (EPR), and mass
      spectroscopy techniques. It is shown that in 50 m M phosphate pH 7. 0-7.4 in the
      absence of other reactants H(2)O(2)induces a concentration-dependent decrease in
      absorption at the Soret band (399 nm) of the microperoxidase, with concomitant
      H(2)O(2)decomposition and oxygen evolution. The reaction causes irreversible heme
      degradation, concomitant with loss of enzymatic activity. Ascorbate effectively
      protects MP11 from degradation and inhibits oxygen evolution. At ascorbate
      concentrations greater than that of H(2)O(2), microperoxidase degradation is
      almost completely prevented. Mass spectrometry showed that H(2)O(2)oxidizes the
      microperoxidase to a monooxygenated product, which did not form if ascorbate was
      included in the reaction system. There appears to be a 1:1 relationship between
      H(2)O(2)degradation and ascorbate oxidation. EPR experiments revealed that an
      ascorbate radical was formed during the reaction. These reactions may be
      described by a scheme where a putative 'compound I' of the microperoxidase is
      reduced by ascorbate back to the original redox state (ferric) of the peroxidase
      in two one-electron steps, concomitantly with oxidation of the ascorbate to an
      ascorbate radical or in one two-electron transfer step forming dehydroascorbate.
      In the absence of ascorbate, the 'compound I' reacts further with the peroxide
      causing microperoxidase degradation and partial oxygen evolution. These
      observations are relevant to the interaction of ferrihemes with H(2)O(2)and
      ascorbic acid and may be pertinent for the potential application of MP11 as an
      anti-cataract agent.

PMID- 10930324
TI  - The major in vivo modifications of the human water-insoluble lens crystallins are
      disulfide bonds, deamidation, methionine oxidation and backbone cleavage.
AB  - This investigation of the water-insoluble crystallins from human lenses has used
      multiple chromatographic separations to obtain proteins of sufficient purity for
      mass spectrometric analysis. Each fraction was analysed to determine the
      molecular masses of the constituent proteins as well as peptides in tryptic
      digests of these proteins. The major components of the water-insoluble
      crystallins were identified as alphaA- and alphaB-crystallins. In addition,
      gammaS-, betaB1-, gammaD-, betaA3/A1- and betaB2-crystallins were found, in order
      of decreasing abundance. Although there was evidence of some backbone cleavage,
      the predominant forms of alphaA-, alphaB, betaB2-, gammaS- and gammaD-crystallins
      were the intact polypeptide chains. The major modifications distinguishing the
      water-soluble crystallins were increased disulfide bonding, oxidation of Met,
      deamidation of Gln and Asn and backbone cleavage. Of the many reactions
      hypothesized to lead to crystallin insolubility and cataract, these results most
      strongly support metal-catalysed oxidation, deamidation and truncation as
      initiators of conformational changes that favor aggregation.

PMID- 10930326
TI  - High-Resolution Fourier Spectrometry of the (14)N(+)(2) Ion.
AB  - Rotational analyses of the B(2)Sigma(+)(u) --> X(2)Sigma(+)(g) system of the
      (14)N(+)(2) molecule have been extended to include the vibrational levels up to
      v' = 4. Spectral data from 20 bands obtained from high-resolution Fourier
      transform spectrometry of a hollow-cathode and a Pointolite lamp were included in
      the analysis. A global deperturbation yielded molecular parameters of the highly
      perturbed B(2)Sigma state and interaction parameters A(2)Pi(u) approximately
      B(2)Sigma(u) with a standard deviation of 0.011 cm(-1). Rotational term values of
      the B(2)Sigma(+) state were also determined. New perturbations in the
      B(2)Sigma(+) (v = 0) level have been observed at N approximately 85 and N
      approximately 96. Copyright 2000 Academic Press.

PMID- 10930325
TI  - Bax-dependent and independent pathways of retinal ganglion cell death induced by
      different damaging stimuli.

PMID- 10930327
TI  - Fourier Transform Infrared Emission Spectroscopy of SeH.
AB  - The infrared vibration-rotation bands of SeH have been measured in the X(2)Pi
      ground state using a Fourier transform spectrometer. The bands were observed in a
      microwave discharge of a mixture of H(2) and Se in the presence of He. The
      rotational structure of the 1-0, 2-1, 3-2 bands of the X(2)Pi(3/2) spin component
      and the 1-0 band of X(2)Pi(1/2) spin component has been observed in the 1800-2600
      cm(-1) region. The principal ground state molecular constants obtained are
      omega(e) = 2421.7153(234) cm(-1), omega(e)x(e) = 44.6012(110) cm(-1),
      omega(e)y(e) = 0.20697(236) cm(-1), B(e) = 7.899187(696) cm(-1), alpha(e) =
      0.220749(399) cm(-1), and r(e) = 1.464319(64) A. This work is the first
      determination of the equilibrium molecular constants of the X(2)Pi state of SeH.
      Copyright 2000 Academic Press.

PMID- 10930328
TI  - The (22(0)1-00(0)0) Band of CO(2) at 6348 cm(-1): Linestrengths, Broadening
      Parameters, and Pressure Shifts.
AB  - The (22(0)1-00(0)0) combination band of CO(2) around 6348 cm(-1) is studied with
      diode-laser spectroscopy, and linestrengths, collision-broadening parameters, and
      pressure shifts are determined. Linestrengths are modeled with a third-order
      Herman-Wallis expansion, and discrepancies with values reported in the literature
      are explained. Copyright 2000 Academic Press.

PMID- 10930329
TI  - The 5V(OH) Overtone Transition of HDO.
AB  - The absorption spectrum of HDO has been recorded by intracavity laser absorption
      spectroscopy in the 16 540-17 055 cm(-1) spectral region corresponding to the
      5nu(3) band centered at 16 920 cm(-1). The (0 0 5) vibrational state is found to
      be mostly isolated from the nearby rovibrational states. The corresponding
      rovibrational transitions were analyzed and fitted in the frame of the effective
      rotational Hamiltonian model in Pade-Borel approximants form. The spectroscopic
      parameters retrieved from the fitting reproduce 100 of the 109 determined energy
      levels with the root-mean-square deviation of 0.0072 cm(-1), close to the
      experimental accuracy. From the integrated relative intensities of a- and b-type
      transitions, the angle between the transition moment and the OH bond is estimated
      to be 46.4 degrees. This value is consistent with an increasing tilt of the
      transition dipole moment, away from the OH bond, when the OH stretching is
      excited. The evolution of the orientation of the transition dipole moment versus
      the vibrational excitation is then compared for the OH and OD overtone bands.
      Copyright 2000 Academic Press.

PMID- 10930330
TI  - Fluorescence Excitation Spectrum of a (2)Pi(3/2)-(2)Pi(3/2) Transition of NiF.
AB  - In this study, a supersonic beam of NiF was produced by the reaction of SF(6)
      with a dc discharge-sputtering source of nickel atoms. The laser-induced
      fluorescence excitation spectrum of a (2)Pi(3/2)-(2)Pi(3/2) transition has been
      recorded in the range of 500-520 nm and rotational structure of 506.5-nm band
      analyzed under the 30 K rotational temperature. Our data are consistent with a
      (2)Pi(3/2) ground state for NiF. The lifetime of this band is measured. Copyright
      2000 Academic Press.

PMID- 10930331
TI  - Line-Mixing Effects in He- and N(2)-Broadened Sigma <-- Pi Infrared Q Branches of
      C(2)H(2).
AB  - Two Q branches of C(2)H(2) near 716.3 and 719.9 cm(-1) belonging to the (nu(4) +
      nu(5))(0) - nu(1f)(4) and 2nu(0)(5)-nu(1f)(5) bands, of Sigma <-- Pi symmetry,
      have been studied for He and N(2) perturbers at pressures ranging from 0.05 to 1
      atm, using a tunable diode-laser spectrometer. To interpret the line-mixing
      effects observed in these spectra, we have applied a model based on the energy
      corrected sudden approximation whose parameters have been only derived from line
      broadening data. This model provides satisfactory agreement with experimental
      bandshapes for both bands and perturbers, especially at pressures higher than 0.1
      atm. The Q-branch profiles for C(2)H(2)-He are higher and narrower than those
      obtained for C(2)H(2)-N(2) at the same pressure as the result of smaller
      broadening coefficients and larger line-mixing effects in the former system.
      Copyright 2000 Academic Press.

PMID- 10930332
TI  - The Radial Hamiltonians for the X(1)Sigma(+) and B(1)Sigma(+) States of HCl.
AB  - All literature vibration-rotational and pure rotational transition energies for
      the ground X(1)Sigma(+) electronic state of H(35)Cl, H(37)Cl, D(35)Cl, and
      D(37)Cl, along with the entire collection of electronic B(1)Sigma(+) -->
      X(1)Sigma(+) emission data for the four isotopomers, have been used in a least
      squares fit of compact analytic Born-Oppenheimer potential functions for the
      B(1)Sigma(+) and X(1)Sigma(+) electronic states. Additional functions related to
      the adiabatic and nonadiabatic corrections have also been determined. Separate
      least-squares fits were made according to the hamiltonian operators of J. K. G.
      Watson (J. Mol. Spectrosc. 80, 411 (1980)) and R. M. Herman and J. F. Ogilvie
      (Adv. Chem. Phys. 103, 187 (1998)). The results from the separate analyses
      demonstrate clearly that the two hamiltonian operators are essentially
      equivalent, both achieving equally satisfactory representations of the spectral
      data, and furnishing virtually identical Born-Oppenheimer potential functions.
      Fully quantum-mechanical vibrational eigenvalues and rotational perturbation
      series parameters B(v)-O(v) are presented for the lower levels of the
      X(1)Sigma(+) ground state for which infrared and/or microwave data are available
      (v" </= 7 for H(35)Cl and H(37)Cl, v" </= 10 for D(35)Cl and D(37)Cl). These
      parameters collectively reproduce the corresponding spectroscopic line positions
      included in our fit to within the uncertainties of the measurements. Copyright
      2000 Academic Press.

PMID- 10930333
TI  - The E(2)Sigma(+) --> C(2)Pi Transition of NO and Term Values for the A, D, E, and
      C Lowest Rydberg Levels.
AB  - The E(2)Sigma(+) --> C(2)Pi Rydberg-Rydberg transition of (14)N(16)O near 8492
      cm(-1) has been studied by Fourier transform spectrometry in the emission from a
      dc excited supersonic jet expansion and from a dc discharge under equilibrium
      conditions. The same transition has also been observed in laser-induced
      stimulated emission. Line wavenumbers of the 0-0, 1-1, and 2-2 bands, together
      with data for previously published near-infrared transitions, have been reduced
      to consistent sets of rovibronic term values for v = 0, 1, and 2 of the
      A(2)Sigma(+), D(2)Sigma(+), E(2)Sigma(+), and C(2)Pi states which frequently
      serve as intermediates in the multiphoton excitation of higher Rydberg levels of
      NO. Copyright 2000 Academic Press.

PMID- 10930334
TI  - Experimental Structures of the Carbon Chains HC(7)N, HC(9)N, and HC(11)N by
      Isotopic Substitution.
AB  - The effective structures (r(0)) of the three linear cyanopolyynes HC(7)N, HC(9)N,
      and HC(11)N have been determined to high accuracy by isotopic substitution,
      following detection in a supersonic molecular beam with a Fourier transform
      microwave spectrometer of all of the singly substituted rare isotopic species.
      For each chain, the lengths of the individual bonds have been determined to an
      accuracy of 0.001 A or 0.1% toward the end of the chain and to 0.01 A or 1.0%
      toward the center. The experimental structures are in excellent agreement with
      recent high-level theoretical calculations, or, in the case of HC(11)N, with
      extrapolation from HC(9)N. The three polyynes studied here represent the largest
      reactive carbon chain molecules for which accurate structures have been derived
      empirically. For HC(7)N and HC(9)N, it has been possible to resolve at high
      resolution nitrogen hyperfine structure in the lower rotational transitions and
      determine eQq for all of the singly substituted isotopic species of HC(7)N and
      for normal HC(9)N. Copyright 2000 Academic Press.

PMID- 10930335
TI  - Harmonic Force Fields from Scaled SCF Calculations: Program ASYM40.
AB  - We report an extended version of our normal coordinate program ASYM40, which may
      be used to transform Cartesian force constants from ab initio calculations to a
      force field in nonredundant internal (symmetry) coordinates. When experimental
      data are available, scale factors for the theoretical force field may then be
      optimized by least-squares refinement. The alternative of refining an empirical
      force field to fit a wide variety of data, as with the previous version ASYM20,
      has been retained. We compare the results of least-squares refinement of the full
      harmonic force field with least-squares refinement of only the scale factors for
      an SCF calculated force field and conclude that the latter approach may be useful
      for large molecules where more sophisticated calculations are impractical. The
      refinement of scale factors for a theoretical force field is also useful when
      there are only limited spectroscopic data. The program will accept ab initio
      calculated force fields from any program that presents Cartesian force constants
      as output. The program is available through Quantum Chemistry Program Exchange.
      Copyright 2000 Academic Press.

PMID- 10930336
TI  - Near-Infrared Laser Spectroscopy of TiS: The b(1)Pi-X(3)Delta Transition.
AB  - Laser-induced fluorescence spectrum of TiS in the 769-863 nm region has been
      recorded and analyzed. The TiS molecule was produced using the technique of laser
      vaporization/reaction with supersonic cooling. Twenty-one weak subbands have been
      assigned as being due to b(1)Pi-X(3)Delta, B(3)Pi(0)-X(3)Delta(1), and C(3)Delta
      X(3)Delta transitions. Strong evidence shows that the b(1)Pi state is responsible
      for perturbing the v = 0, 1, and 2 levels of the C(3)Delta(1) subband. The
      molecular constants of the b(1)Pi state have been determined as follows: T(e) =
      10 589.47 cm(-1), omega(e) = 542.14 cm(-1), omega(e)x(e) = 3.16 cm(-1), B(e) =
      0.19568 cm(-1), and alpha(e) = 0.00085 cm(-1). The spin-orbit interaction between
      the b(1)Pi (v = 2 and 3) and C(3)Delta (v = 1 and 2) levels is discussed in terms
      of configuration interaction occurring between the b(1)Pi from the 11varsigma(1)
      5pi(1) configuration and the (1)Pi from the 5pi(1) 1delta(1) configuration, and
      the C(3)Delta state from 12varsigma(1) 1delta(1) configuration. Copyright 2000
      Academic Press.

PMID- 10930337
TI  - The Pure Rotational Spectra of AuCl and AuBr.
AB  - The pure rotational spectra of AuCl and AuBr have been measured in the v = 0 and
      1 (also for v = 2 for Au(35)Cl) vibrational states in the 5-22 GHz spectral
      region using a cavity pulsed-jet Fourier transform microwave spectrometer. The
      molecules were prepared by ablating Au metal in the presence of Cl(2) or Br(2)
      entrained in the Ar or Ne backing gas of the jet. The equilibrium internuclear
      distances r(e) have been determined along with estimates of the harmonic
      vibration frequencies and the dissociation energies. The ionic characters of the
      AuCl and AuBr bonds have been estimated from the halogen nuclear quadrupole
      coupling constants to be i(c) approximately 38%. The gold nuclear quadrupole
      coupling constants change appreciably from AuF to AuCl to AuBr (including a sign
      change), indicating substantial differences in their electronic structures at Au;
      these variations could not be accounted for with a simple Townes-Dailey
      calculation. Copyright 2000 Academic Press.

PMID- 10930338
TI  - Torsional Splitting in the Degenerate Vibrational States of (70)Ge(2)H(6):
      Rotation-Torsion Analysis of the nu(7) and nu(9) Fundamentals.
AB  - The rotational and torsional structure of the nu(7) and nu(9) degenerate
      fundamentals of (70)Ge(2)H(6) has been analyzed under high resolution. The
      torsional structure of both v(7) = 1 and v(9) = 1 states can be fitted by a
      simple one-parameter formula. The x,y-Coriolis interaction with the parallel
      nu(5) fundamental was accounted for in the analysis of nu(7). A strong
      perturbation of the J structure of the E(3s) torsional component of the KDeltaK =
      -2 subbranches of nu(9) can be explained by the resonance with an E(3s) excited
      level of the pure torsional manifold. The perturber is centered at 361.58 cm(-1),
      very close to the value estimated with a barrier height of 285 cm(-1). This
      confirms that the fundamental torsional wavenumber is close to 103 cm(-1), in
      good agreement with the "ab initio" prediction. The torsional splittings of all
      the infrared active degenerate fundamentals, nu(7), nu(8), and nu(9), follow the
      trend predicted by theory, and have been fitted by exploratory calculations
      accounting only for the torsional Coriolis-coupling mechanism of all degenerate
      vibrational fundamentals in several torsional states. This confirms that
      torsional Coriolis coupling is the dominant mechanism responsible for the
      decrease of the torsional splitting in the degenerate vibrational states. A
      higher value of the barrier had to be used for the nu(9) mode. Copyright 2000
      Academic Press.

PMID- 10930339
TI  - The KRb (2)(3)Sigma(+) Electronic State.
AB  - High-resolution spectra of the (3)(1)Pi --> (2)(3)Sigma(+) system of the KRb
      molecule, obtained after excitation with fixed frequencies Ar(+) laser lines,
      were recorded on a Connes-type Fourier transform interferometer. Molecular
      constants of the first 14 vibrational levels of the (2)(3)Sigma(+) state are
      determined. The RKR potential energy curve is derived. The main spectroscopic
      constants for this triplet electronic state of the (39)K (85)Rb isotopic species
      are T(e) = 13 507.146(2) cm(-1), omega(e) = 48.6385(6) cm(-1), B(e) =
      0.0254152(5) cm(-1), gamma = 0.00164(4) cm(-1), epsilon = -0.469(2) cm(-1), R(e)
      = 4.98345 A, &Dscr;(e) = 3447 cm(-1). Copyright 2000 Academic Press.

PMID- 10930340
TI  - Analysis of the (0 0 v(3)), v(3) = 1, 2, 3 Vibrotational States of HDSe.
AB  - High-resolution Fourier transform spectra of HDSe in the region of the 2nu(3) and
      3nu(3) bands were recorded and analyzed for five different (M)Se isotopic HDSe
      species. Energies obtained from rovibrational analyses of the (002) and (003)
      states, together with those taken of the (001) state from an earlier study [O. N.
      Ulenov, G. A. Onopenko, N. E. Tyabaeva, H. Burger, and W. Jerzembeck, J. Mol.
      Spectrosc. 198, 27-39 (1999)], were used as input information for a "Global Fit"
      procedure. This fit provided 34 spectroscopic parameters for the HD(80)Se species
      which reproduced rotational-vibrational transitions of the (001), (002), and
      (003) states within experimental accuracy. Corresponding analyses were performed
      for the other (M)Se (M = 82, 78, 77, and 76) species. Copyright 2000 Academic
      Press.

PMID- 10930341
TI  - Double-Modulation Submillimeter-Wave Spectroscopy of HOC(+) in the nu(2) Excited
      Vibrational State.
AB  - The submillimeter-wave rotational transitions of HOC(+) in the nu(2) excited
      state are first detected using the double-modulation method, and the precise
      transition frequencies and the much improved molecular constants are obtained.
      The measurements of the ground state HOC(+) and DOC(+) submillimeter-wave lines
      are extended up to the 840-GHz region. It is found that the higher order
      centrifugal distortion constant, H, is necessary to fit the observed transition
      frequencies to the experimental accuracy. Copyright 2000 Academic Press.

PMID- 10930342
TI  - Vibrational Spectra of cis and trans Oxalyl Fluoride and Their Site-Selective IR
      Induced Rotamerization in an Argon Matrix.
AB  - A cis/trans equilibrium mixture of matrix-isolated oxalyl fluoride was irradiated
      with a narrowband tunable IR source in the 2nu (CO) spectral region (3680-3710
      cm(-1)). Rotamerization of cis into trans and vice versa was achieved (even site
      selective) by selective IR pumping. The experiments strongly aided a detailed IR
      analysis of both rotamers. For a complete vibrational analysis, low-temperature
      Raman measurements were also performed. With the exception of the torsional
      vibration of cis oxalyl fluoride, all the fundamentals of both rotamers have been
      observed. Copyright 2000 Academic Press.

PMID- 10930343
TI  - High-Resolution Spectroscopy of Jet-Cooled (32)SO(2) and (34)SO(2): The a(3)B(1)
      ;X(1)A(1), 2(1)(0) and 1(1)(0) Bands.
AB  - Laser-induced excitation spectra of the two bands a(3)B(1)-;X(1)A(1), 2(1)(0) and
      1(1)(0) of (32)SO(2) and (34)SO(2) have been recorded in a supersonic jet at a
      resolution of 0.015 cm(-1). The rotational and electron-spin fine structure has
      been analyzed for both isotopic species. Analysis of the rotational and electron
      spin fine structure yields precise values of the rotational constants A, B, and C
      and the spin constants alpha and beta for both (32)SO(2) and (34)SO(2) in the
      states a(3)B(1) (010) and (100). No interaction between these two vibrational
      states with any nearby triplet state is observed for rotational levels with J </=
      8 and K </= 2. Copyright 2000 Academic Press.

PMID- 10930344
TI  - Photoacoustic Detection of New Bands of HCN between 11 390 and 13 020 cm(-1).
AB  - A laser photoacoustic technique has been used to measure the absorption spectrum
      of HCN in the region from 11 390 to 13 020 cm(-1) with a resolution that is
      limited by the Doppler- and pressure-broadened linewidth. This is a very
      sensitive technique that has allowed us to measure very weak bands with a small
      volume of gas. These measurements provide the rovibrational constants for a
      number of newly observed vibrational energy levels. Copyright 2000 Academic
      Press.

PMID- 10930345
TI  - N(2)-Broadening Coefficients in the nu(1) Band of (35)Cl(12)C(14)N.
AB  - N(2)-broadening coefficients have been measured for 30 lines of cyanogen chloride
      ((35)Cl(12)C(14)N) at room temperature in the P and R branches of the nu(1) band,
      using a tunable diode-laser spectrometer. These lines, with J values ranging from
      0 to 55, are located in the spectral range 694-736 cm(-1). The collisional widths
      are obtained by fitting the spectral lines with a Voigt and a Rautian profile.
      The broadenings coefficients of (35)ClCN-N(2) have also been calculated from a
      semiclassical theory involving the atom-atom Lennard-Jones model for the
      intermolecular potential in addition to electrostatic interaction. Copyright 2000
      Academic Press.

PMID- 10930346
TI  - Approximate Selection Rules for |K| = 1-0 and 1-1 Tunneling-Rotation Transitions
      in the Methanol Dimer.
AB  - Approximate K = 0 and |K| = 1 tunneling-rotation eigenfunctions for the four A,
      four E, and one G symmetry species present in the methanol dimer, derived from
      molecular parameters obtained previously from a least-squares fit to transition
      frequencies involving K = 0 and 1 levels, are used to clarify some apparent
      contradictions associated with traditional b- and c-type transition designations
      in the E and G tunneling-rotational states of this dimer. These approximate
      eigenfunctions also predict strong and weak line intensities which are consistent
      with the pattern of strong a-, b-, and c-type transitions observed, thus
      supporting our previous separate K-state analysis based only on energy level
      differences. Some of the predicted weaker |K| = 1 a-type transitions should be
      experimentally observable with more signal averaging. Copyright 2000 Academic
      Press.

PMID- 10930348
TI  - Fourier Transform Spectroscopy of Chemiluminescence from the SrO A(1)Sigma(+)
      X(1)Sigma(+) Transition.
AB  - The A(1)Sigma(+)-X(1)Sigma(+) chemiluminescence spectrum of SrO was observed
      using a Fourier transform spectrometer. SrO was produced in a Broida-type oven
      from the Sr + N(2)O reaction. A total of 75 bands from (88)SrO, (87)SrO, and
      (86)SrO were measured in the range of 7600-13 600 cm(-1) at a resolution of 0.04
      cm(-1). The vibrational levels of the ground state were observed up to v" = 12
      and over 10 000 rovibrational lines with J as high as 153 were analyzed at a
      precision of about 0.005 cm(-1). Significantly improved spectral constants for
      the ground state were obtained by representing the perturbed excited state by
      term values and by adding the known microwave data and infrared data to our fit.
      Strong perturbations were observed in the upper A state. The vibrational levels
      of the A(1)Sigma(+) state were measured up to v' = 8 and some new perturbations
      are reported. Copyright 2000 Academic Press.

PMID- 10930347
TI  - Evidence of Vibrational-Induced Rotational Axis Switching for HD(12)C(16)O: New
      High-Resolution Analysis of the nu(5) and nu(6) Bands and First Analysis of the
      nu(4) Band (10-um Region).
AB  - Using new high-resolution Fourier transform spectra recorded in Giessen in the 8
      12 um region, a more extended analysis of the nu(5) and nu(6) bands and the first
      high-resolution study of the nu(4) band of HDCO were performed. As pointed out
      previously [M. Allegrini, J. W. C. Johns, and A. R. W. McKellar, Can. J. Phys.
      56, 859-864 (1978)], the energy levels of the 5(1) and 6(1) states are strongly
      coupled by A- and B-type Coriolis interactions. On the other hand, it appeared
      that weaker resonances involving the energy levels of the 4(1) state with those
      of the 5(1) and 6(1) states also had to be accounted for. Consequently, the
      calculation of the energy levels was performed taking into account the Coriolis
      type resonances linking the energy levels of the {6(1), 5(1), 4(1)} resonating
      states. Because of the unusually strong Coriolis interaction between nu(5) and
      nu(6), a nonclassical behavior of the rotational levels of the 5(1) and 6(1)
      states was observed and it was necessary to use a new Hamiltonian matrix which
      possesses, as usual, both A- and B-type Coriolis operators in the 5(1) if 6(1)
      and 6(1) if 4(1) off diagonal blocks but differs from the classical reduced
      Hamiltonian which is used commonly for planar C(s)-type molecules. More
      precisely, it proved necessary to include non-orthorhombic terms in the expansion
      of the rotational Hamiltonian of the 5(1) and 6(1) states. According to the
      considerations developed by Watson [J. K. G. Watson, in "Vibrational Spectra and
      Structure," (J. Durig, Ed.), Chap. 1, Elsevier, Amsterdam, 1977], these non
      orthorhombic operators which are not symmetry forbidden are usually removed for
      semirigid C(s)-type molecules by rotational contact transformations. In the
      present study, the occurrence of terms in {J(x), J(z)} in the expansions of the
      rotational Hamiltonians for the 5(1) and 6(1) states indicates that the inertial
      system of HDCO differs for each of the three {6(1), 5(1), 4(1)} resonating
      states. Therefore, HDCO becomes a good example of vibrational-induced rotational
      axis switching (VIRAS) which was already suggested as the mechanism responsible
      for the enhanced densities of coupled states observed in 2-fluoroethanol [H. Li,
      S. Erza, and L. A. Philips, J. Chem. Phys. 97, 5956-5963 (1992)]. Copyright 2000
      Academic Press.

PMID- 10930349
TI  - First Observation of the Forbidden k-X Transition of (13)C(16)O.
AB  - A weak rotationally resolved absorption band of (13)C(16)O has been identified
      from photographic spectra at 1078 A and assigned to the forbidden transition from
      the X(1)Sigma(+) (v = 0) ground state to the k(3)Pi (v = 3) valence state. It is
      similar in structure to the corresponding band of (12)C(16)O but due to the fact
      it was photographed at a relatively low pressure only the two strongest
      rotational branches could be positively identified. It is the first time that the
      forbidden k-X transition has been observed for (13)C(16)O. The measured isotopic
      shift in the band origin provides independent confirmation of the new vibrational
      assignment of the k state by G. Berden, R. T. Jongma, D. Van der Zande, and G.
      Meijer (J. Chem. Phys. 107, 8303-8310 (1997)). Copyright 2000 Academic Press.

PMID- 10930350
TI  - A Note on Internal Rotation-Rotation Interactions in Ethyl Alcohol.

PMID- 10930351
TI  - Accurate Equilibrium Structures and Equilibrium Dipole Moments for CH(3)CNH(+)
      and CH(3)C(3)NH(+).

PMID- 10930352
TI  - Precision Broadband Spectroscopy near 2 THz: Frequency-Stabilized Laser Sideband
      Spectrometer with Backward-Wave Oscillators.

PMID- 10930353
TI  - Isoprostanes: generation, pharmacology, and roles in free-radical-mediated
      effects in the lung.
AB  - Isoprostanes are produced during peroxidation of membrane lipids by free radicals
      and reactive oxygen species, and are currently used as markers of many disease
      states and experimental conditions in which oxidative stress is a prominent
      feature. A small number of reports have described the ability of some
      isoprostanes to evoke important biological effects in smooth muscle and other
      cell types. However, most of these studies were done using rat tissues, and only
      two specific isoprostanes - 8-iso-PGE(2)and 8-iso-PGF(2alpha)- were tested. In
      this review, we describe the generation of isoprostanes during oxidative stress,
      and their effects on smooth muscle, including our novel findings of their effects
      on human airway, pulmonary artery and pulmonary vein smooth muscles.
      Collectively, the data suggest that isoprostanes may not only be markers, but may
      in fact mediate the effects of free radicals and reactive oxygen species.

PMID- 10930354
TI  - Accumulation of nitrotyrosine correlates with endothelial NO synthase in
      pulmonary resistance arteries during chronic hypoxia in the rat.
AB  - Nitrotyrosine and eNOS were detected immunocytochemically using specific
      antibodies in paraffin sections of lung from rats subjected to hypoxia for 2, 7,
      or 14 days. The staining intensity for eNOS was enhanced in the endothelium of
      both resistance and conduit pulmonary arteries at 2 days. Staining intensity for
      eNOS remained elevated at 7 and 14 days in conduit arteries, whereas it
      progressively increased further in resistance arteries. Nitrotyrosine staining
      was elevated to a similar degree in endothelium and adjacent vascular smooth
      muscle. In resistance pulmonary arteries, there was a progressive increase in
      nitrotyrosine, which matched the increase in eNOS. In conduit pulmonary arteries,
      nitrotyrosine increased only after 14 days of hypoxia. The results suggest that
      in chronic hypoxia the up-regulation of eNOS leads to the formation of
      peroxynitrite which has access to both endothelium and vascular smooth muscle.

PMID- 10930355
TI  - Inhibition by SR 59119A of isoprenaline-, forskolin- and VIP-induced relaxation
      of human isolated bronchi.
AB  - In the human isolated bronchus (HIB) it has been shown that beta(3)-adrenoceptor
      stimulation fails to induce relaxation of airway smooth muscle. It has however
      been reported in human ventricular endomyocardial biopsies that beta(3)
      adrenoceptor stimulation induced a marked negative inotropic effect which could
      be linked to Gi protein activation. The aims of this study were: (1) to determine
      in HIB (internal diameter 1-2 mm) whether the selective beta(3)-adrenoceptor
      agonist SR 59119A (N[7-methoxy-1,2,3, 4-tetrahydronaphthalen-(2R)methyl]-(2R)-2
      hydroxy-2-(3-chloroph eny l)e thanamine hydrochloride) was able to inhibit
      adenylate-cyclase-mediated airway smooth muscle relaxation induced by
      isoprenaline, forskolin or vasoactive intestinal peptide (VIP) and (2) to
      investigate the role of the Gi protein in this interaction. SR 59119A (0.1 microM
      and 1 microM) induced a shift to the right of concentration response curve for
      isoprenaline (-0. 15+/-0.06 and -0.54+/-0.21 log unit, P<0.05 and P<0.01
      respectively), forskolin (-0.12+/-0.02 and -0.30+/-0.05 log unit, P<0.001), and
      VIP (-0.42+/-0.12 log unit, P<0.01 with SR59119A 10(-6)M). The inhibitory effect
      of SR 59119A was (1) abolished by an incubation of HIB with pertussis toxin (1
      microg/ml, during 15 h in Krebs-Henseleit solution, at 21 degrees C), which is
      known to inactivate the Gi protein and (2) increased after an incubation of HIB
      with the pro-inflammatory cytokine IL-1beta (10 ng/ml, during 15 h in Krebs
      Henseleit solution, at 21 degrees C), which is known to up-regulate Gi protein
      expression. Our results suggest that the selective beta(3)-adrenoceptor agonist
      SR59119A might inhibit the cAMP-dependent relaxation of human isolated bronchus
      through Gi protein-mediated inhibition of adenylate cyclase.

PMID- 10930356
TI  - Comparison of urinary desmosine excretion in patients with chronic obstructive
      pulmonary disease or cystic fibrosis.
AB  - Neutrophil elastase is involved in the pathogenesis of several pulmonary
      diseases; a strategy for monitoring in vivo elastase activity is to measure
      changes in biochemical markers. The objective of this study was to determine
      whether differences in the urinary excretion of the elastin crosslinks, desmosine
      and isodesmosine (which are unique amino acid products of elastase activity),
      could be discerned between groups of patients with chronic obstructive pulmonary
      disease (COPD) or cystic fibrosis (CF), and non-diseased, age-matched controls.
      Twenty-four-hour urine collections were analysed to eliminate variations in
      excretion throughout the day, and urine was collected on four separate days in 29
      31 subjects/group to investigate the variability in desmosines excretion among
      the groups. Both sets of patient populations had significantly more variable
      desmosines readings (higher standard deviations) relative to their respective age
      matched control group. The means for three adult groups (COPD, controls and a
      COPD-smoker subset) ranged from 28.4 to 35.5 pmol desmosines/mg creatinine and
      there were no differences among the groups. Values in children were higher: 55
      pmol desmosines/mg creatinine in the non-CF children and 77 pmol desmosines/mg
      creatinine for the CF group (P<0.01 vs. age-matched controls). The results of
      this study show that urinary desmosines, as a surrogate marker for enhanced
      elastase activity, are more highly variant in both patient populations relative
      to age-matched controls, and an overall increase in the mean value is further
      observed in patients with cystic fibrosis.

PMID- 10930357
TI  - Bradykinin-induced airway constriction in guinea-pigs: role of leukotriene D(4).
AB  - Tachykinins (TK) have been implicated in both bradykinin-(BK) and hyperpnea
      induced broncho-constriction (HIB) in the guinea-pig. However, TKs appear to have
      an indirect effect in HIB by releasing leukotriene (LT)D(4). We postulated that
      BK may cause bronchoconstriction through a cascade involving TK and LTD(4). We
      examined the role of TK and LTD(4)in BK-induced bronchoconstriction in ventilated
      Hartley guinea-pigs. Respiratory resistance (R(rs)) was monitored for 2 h
      following insufflation of BK (150 nM). Animals were pretreated with propranolol,
      then with either neurokinin (NK)1 (CP-99,994)+NK2 (SR-48,968) receptor
      antagonists or pranlukast (90 microg or 900 microg), an LTD(4)antagonist. Control
      animals received no pretreatment. BK-induced bronchoconstriction was
      significantly lower in NK1/NK2 (128%+/-6% baseline R(rs)SEM) and pranlukast (90
      microg; 205+/-22, 900 microg; 169+/-20) animals compared to controls (284+/-22),
      P<0.0001 ANOVA. Bile from control and saline challenged animals was analysed for
      LTD(4)by HPLC and radio-immunoassay. However, LTD(4)excretion rate showed no
      significant difference over a 2-h collection period following insufflation of
      either BK or saline, respectively; baseline =2.5 pmol/h+/-0.6 SEM vs. 2.3+/-0.2,
      0-1 h=2.8+/-0.7 vs. 2.0+/-0.6, 1-2 h=2.3+/-0.6 vs. 1.7+/-0.7. We conclude that BK
      induced bronchoconstriction is mediated in part through the release of both TK
      and LTD(4), but the latter is released in insufficient quantities to be
      detectable by biliary analysis.

PMID- 10930358
TI  - Efficacy of IV aminophylline as a supplemental therapy in moderate broncho
      obstructive crisis in infants and preschool children.
AB  - The aim of the present study was to investigate the efficacy of iv aminophylline
      as a supplemental therapy for wheezy infants and preschool children who still
      present moderate broncho-obstruction after treatment with nebulized fenoterol. A
      prospective randomized, double blind, placebo-controlled trial was conducted in a
      Paediatric Emergency Room. The major selection criteria for patients>> inclusion
      were age between 1 and 7 years, a wheezy episode lasting less than 2 days which
      failed to respond to three sequential fenoterol nebulizations, a Wood-Downes
      score between 3 and 6, and a history of at least two similar episodes. Exclusion
      criteria were radiologically-identified pulmonary condensation, recent use of
      corticosteroid and/or theophylline drugs, and previous diagnosis of chronic
      conditions. A sample of 43 cases was selected: 24 in Group A and 19 in Control
      Group B. All patients were submitted to nebulization with fenoterol and
      intravenous hydrocortisone for a maximum period of 24 h. Only Group A patients
      received iv aminophylline (6 mg/kg in bolus and 1.2 mg/kg per h for maintenance
      schedule). Treatment efficacy parameters established for the two groups were
      based on the Wood-Downes clinical score. Throughout the study, the average
      clinical scores and the discharge rate were similar for both groups. The average
      stay in the Emergency Room was 12.5 h for Group A and 14.6 h for Control Group B.
      In conclusion, the use of supplemental iv aminophylline for moderate broncho
      obstructive crisis in wheezy infants and preschool children did not add
      therapeutically significant results to the usually prescribed combination of
      nebulized beta-adrenergic and intravenous corticosteroid drugs.

PMID- 10930359
TI  - A locus for an autosomal dominant form of progressive renal failure and
      hypertension at chromosome 1q21.
AB  - Linkage studies were performed in a large family with an autosomal dominant
      phenotype characterized by nephropathy and hypertension. In this family of Iraqi
      Jewish origin, the nephropathy develops into progressive renal failure. By
      performing a genomewide linkage search, we localized the disease gene to
      chromosome 1q21; the highest LOD score was obtained for the marker at locus
      D1S305, which yielded a maximum LOD score of 4.71 at a recombination fraction of
      0. Recombination mapping defined an interval of approximately 11.6 cM, between
      the markers at loci D1S2696 and D1S2635, that contains the disease gene.
      Localization of the disease-causing gene in this family represents a necessary
      step toward isolation of the defective gene and toward a deeper understanding of
      the mechanisms of hypertension and progressive renal failure.

PMID- 10930360
TI  - Polymorphisms in genes involved in folate metabolism as maternal risk factors for
      Down syndrome.
AB  - Down syndrome is a complex genetic and metabolic disorder attributed to the
      presence of three copies of chromosome 21. The extra chromosome derives from the
      mother in 93% of cases and is due to abnormal chromosome segregation during
      meiosis (nondisjunction). Except for advanced age at conception, maternal risk
      factors for meiotic nondisjunction are not well established. A recent preliminary
      study suggested that abnormal folate metabolism and the 677C-->T polymorphism in
      the methylenetetrahydrofolate reductase (MTHFR) gene may be maternal risk factors
      for Down syndrome. The present study was undertaken with a larger sample size to
      determine whether the MTHFR 677C-->T polymorphism was associated with increased
      risk of having a child with Down syndrome. Methionine synthase reductase (MTRR)
      is another enzyme essential for normal folate metabolism. A common polymorphism
      in this gene was recently associated with increased risk of neural tube defects
      and might also contribute to increased risk for Down syndrome. The frequencies of
      the MTHFR 677C-->T and MTRR 66A-->G mutations were evaluated in DNA samples from
      157 mothers of children with Down syndrome and 144 control mothers. Odds ratios
      were calculated for each genotype separately and for potential gene-gene
      interactions. The results are consistent with the preliminary observation that
      the MTHFR 677C-->T polymorphism is more prevalent among mothers of children with
      Down syndrome than among control mothers, with an odds ratio of 1.91 (95%
      confidence interval [CI] 1.19-3.05). In addition, the homozygous MTRR 66A-->G
      polymorphism was independently associated with a 2. 57-fold increase in estimated
      risk (95% CI 1.33-4.99). The combined presence of both polymorphisms was
      associated with a greater risk of Down syndrome than was the presence of either
      alone, with an odds ratio of 4.08 (95% CI 1.94-8.56). The two polymorphisms
      appear to act without a multiplicative interaction.

PMID- 10930362
TI  - The renaissance of probiotics and prebiotics.

PMID- 10930363
TI  - Accuracy of helical computed tomographic angiography for the diagnosis of colonic
      angiodysplasia.
AB  - BACKGROUND & AIMS: The diagnosis of colonic angiodysplasia is often challenging
      and relies on endoscopy or catheter angiography. We investigated whether computed
      tomographic angiography (CTA) contributes to the diagnosis of colonic
      angiodysplasia. METHODS: Twenty-eight patients with suspected bleeding from
      colonic angiodysplasia were prospectively evaluated. Gastrointestinal bleeding
      was investigated by colonoscopy plus visceral angiography and by CTA. The level
      of agreement between CTA and the former procedures was determined. RESULTS: CTA
      images of diagnostic quality were obtained in 26 patients. Eighteen patients were
      diagnosed with colonic angiodysplasia by colonoscopy plus visceral angiography,
      and 14 by CTA (kappa = 0.68; P < 0.001). Sensitivity, specificity, and positive
      predictive values of CTA for detection of colonic angiodysplasia were 70%, 100%,
      and 100%, respectively. CTA signs including accumulation of vessels in the
      colonic wall, early filling vein, and supplying enlarged artery were present in
      55%, 50%, and 22% of cases, respectively. None of these signs were present in the
      8 patients with obscure gastrointestinal bleeding and negative diagnostic
      investigation of the digestive tract. CONCLUSIONS: CTA is a sensitive, specific,
      well-tolerated, and minimally invasive tool for the diagnosis of colonic
      angiodysplasia.

PMID- 10930361
TI  - Iron-dependent self-assembly of recombinant yeast frataxin: implications for
      Friedreich ataxia.
AB  - Frataxin deficiency is the primary cause of Friedreich ataxia (FRDA), an
      autosomal recessive cardiodegenerative and neurodegenerative disease. Frataxin is
      a nuclear-encoded mitochondrial protein that is widely conserved among
      eukaryotes. Genetic inactivation of the yeast frataxin homologue (Yfh1p) results
      in mitochondrial iron accumulation and hypersensitivity to oxidative stress.
      Increased iron deposition and evidence of oxidative damage have also been
      observed in cardiac tissue and cultured fibroblasts from patients with FRDA.
      These findings indicate that frataxin is essential for mitochondrial iron
      homeostasis and protection from iron-induced formation of free radicals. The
      functional mechanism of frataxin, however, is still unknown. We have expressed
      the mature form of Yfh1p (mYfh1p) in Escherichia coli and have analyzed its
      function in vitro. Isolated mYfh1p is a soluble monomer (13,783 Da) that contains
      no iron and shows no significant tendency to self-associate. Aerobic addition of
      ferrous iron to mYfh1p results in assembly of regular spherical multimers with a
      molecular mass of approximately 1. 1 MDa (megadaltons) and a diameter of 13+/-2
      nm. Each multimer consists of approximately 60 subunits and can sequester >3,000
      atoms of iron. Titration of mYfh1p with increasing iron concentrations supports a
      stepwise mechanism of multimer assembly. Sequential addition of an iron chelator
      and a reducing agent results in quantitative iron release with concomitant
      disassembly of the multimer, indicating that mYfh1p sequesters iron in an
      available form. In yeast mitochondria, native mYfh1p exists as monomer and a
      higher-order species with a molecular weight >600,000. After addition of (55)Fe
      to the medium, immunoprecipitates of this species contain >16 atoms of (55)Fe per
      molecule of mYfh1p. We propose that iron-dependent self-assembly of recombinant
      mYfh1p reflects a physiological role for frataxin in mitochondrial iron
      sequestration and bioavailability.

PMID- 10930364
TI  - Magnetic resonance colonography versus conventional colonoscopy for the detection
      of colonic endoluminal lesions.
AB  - BACKGROUND & AIMS: The most effective prophylaxis for colorectal cancer is
      endoscopic polypectomy. Prompted by the disadvantages of conventional colonoscopy
      (CC), we assessed the diagnostic ability of a promising alternative technique for
      detecting endoluminal masses: magnetic resonance colonography (MRC). METHODS:
      Seventy consecutive patients referred for CC underwent preliminary MRC. The
      diagnostic ability of this technique in detecting colonic endoluminal lesions was
      determined, compared with that of CC, and related to the findings from histologic
      examination. RESULTS: In detecting endoluminal lesions, MRC achieved a diagnostic
      accuracy similar to CC (sensitivity, 96%; specificity, 93%; positive predictive
      value, 98%; and negative predictive value, 87.5%). CONCLUSIONS: MRC could be
      useful in screening programs of patients at high risk for colon cancer. Patients
      with MRC-detected endoluminal lesions must undergo CC for histologic diagnosis.

PMID- 10930365
TI  - Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis:
      a double-blind, placebo-controlled trial.
AB  - BACKGROUND & AIMS: Pouchitis is the major long-term complication after ileal
      pouch-anal anastomosis for ulcerative colitis. Most patients have relapsing
      disease, and no maintenance treatment study has been performed. We evaluated the
      efficacy of a probiotic preparation (VSL#3) containing 5 x 10(11) per gram of
      viable lyophilized bacteria of 4 strains of lactobacilli, 3 strains of
      bifidobacteria, and 1 strain of Streptococcus salivarius subsp. thermophilus
      compared with placebo in maintenance of remission of chronic pouchitis. METHODS:
      Forty patients in clinical and endoscopic remission were randomized to receive
      either VSL#3, 6 g/day, or an identical placebo for 9 months. Patients were
      assessed clinically every month and endoscopically and histologically every 2
      months or in the case of a relapse. Fecal samples were collected for stool
      culture before and after antibiotic treatment and each month during maintenance
      treatment. RESULTS: Three patients (15%) in the VSL#3 group had relapses within
      the 9-month follow-up period, compared with 20 (100%) in the placebo group (P <
      0.001). Fecal concentration of lactobacilli, bifidobacteria, and S. thermophilus
      increased significantly from baseline levels only in the VSL#3-treated group (P <
      0.01). CONCLUSIONS: These results suggest that oral administration of this new
      probiotic preparation is effective in preventing flare-ups of chronic pouchitis.

PMID- 10930366
TI  - "Atypical p-ANCA" in IBD and hepatobiliary disorders react with a 50-kilodalton
      nuclear envelope protein of neutrophils and myeloid cell lines.
AB  - BACKGROUND & AIMS: Atypical "antineutrophil cytoplasmic antibodies" (ANCA) are
      present in patients with ulcerative colitis (UC), primary sclerosing cholangitis
      (PSC), and autoimmune hepatitis (AIH). Recently, we showed that atypical p-ANCA
      react with nuclear envelope proteins of neutrophils. Based on this observation,
      we aimed to characterize the nuclear antigen recognized by atypical p-ANCA.
      METHODS: We prepared cytoplasmic and nuclear extracts of human neutrophils, human
      HL-60, and murine 32D myeloid cells. Proteins were resolved by 1- and 2
      dimensional gel electrophoresis. Reactive proteins were detected by
      immunoblotting with sera from 118 individuals (UC, 25; PSC, 28; AIH, 35; disease
      and normal controls, 30). Atypical p-ANCA (n = 64) were affinity-purified against
      the reactive protein and investigated for their immunofluorescence pattern using
      confocal microscopy. RESULTS: Immunoblotting showed reactivity to a myeloid
      specific 50-kilodalton nuclear protein with an isoelectric point of pH 6.0
      detected in 92% (59 of 64) of the patients with inflammatory bowel or
      hepatobiliary diseases and atypical p-ANCA. Affinity-purified antibodies against
      the 50-kilodalton protein gave a nuclear rim-like fluorescence on myeloid cells
      examined by immunofluorescence microscopy. Affinity-purified antibodies did not
      recognize antigens in nonmyeloid cells. CONCLUSIONS: Atypical p-ANCA in UC, PSC,
      or AIH recognize a 50-kilodalton myeloid-specific nuclear envelope protein.

PMID- 10930367
TI  - Phenotypic and molecular characteristics of hyperplastic polyposis.
AB  - BACKGROUND & AIMS: Patients with hyperplastic polyposis are reported to have
      multiple and/or large hyperplastic polyps (HPs) and an increased risk of
      colorectal cancer, but the phenotype and genetic alterations in hyperplastic
      polyposis have not been studied in detail. METHODS: We evaluated clinical
      pathological and molecular characteristics of 129 HPs, 6 serrated adenomas, and 3
      admixed hyperplastic-adenomatous polyps from 13 patients with hyperplastic
      polyposis (more than 20 HPs), 5 patients with a large HP (>/=1 cm in diameter),
      and 5 patients with multiple HPs (5-10 HPs). RESULTS: HPs in the right colon in
      contrast to the left colorectum had more frequent topographic dysregulation of
      p21(Waf-1/Cip1) expression (94% vs. 76%, P = 0.03) and of proliferation (92% vs.
      53%, P = 0. 0001), but less frequent allelic loss of chromosome 1p (4% vs. 17%, P
      = 0.03). K-ras mutation was present in 8% of HPs, p53 gene product overexpression
      in none, and microsatellite instability in 3% without relationship to
      microsatellite instability in synchronous cancer. Patients with a large HP
      differed from those with multiple HPs in having a high frequency of right-sided
      HP (63% vs. 22%, P = 0.01) and of right-sided colon cancer (100% vs. 8%, P =
      0.003). Hyperplastic polyposis was associated with a family history of colorectal
      cancer (P = 0.01) and with loss of chromosome 1p in HP (21% vs. 0%, P = 0.001).
      CONCLUSIONS: A hyperplastic polyp/dysplasia-to-adenocarcinoma sequence can be
      manifested in 3 distinct phenotypes consisting of patients with hyperplastic
      polyposis and chromosome 1p allelic loss in some HPs, in contrast to patients who
      have large, right-sided HPs or small numbers of HPs that lack 1p loss.

PMID- 10930368
TI  - Is there publication bias in the reporting of cancer risk in Barrett's esophagus?
AB  - BACKGROUND & AIMS: The published risk of adenocarcinoma in the setting of
      Barrett's esophagus (BE) varies. Publication bias, the selective reporting of
      studies featuring positive or extreme results, may result in overestimation of
      this cancer risk in the literature. The aim of this study was to assess those
      publications reporting a cancer risk in BE for evidence of publication bias.
      METHODS: A MEDLINE search for all published estimates between 1966 and 1998 of
      cancer risk in BE was performed. All studies reporting a cancer risk expressible
      in cancers per patient-year of follow-up were retrieved. Bibliographies of these
      studies were surveyed for additional estimates. All publications that required an
      initial endoscopy with histologic confirmation of BE and any cancer were
      included. The relationship of reported cancer risk to size of the study was
      assessed. Multivariable regression controlling for differences in definition of
      BE, as well as other study characteristics, was performed. The data were also
      analyzed by means of a funnel diagram, an epidemiologic method to assess
      publication bias. RESULTS: Five hundred fifty-four abstracts were reviewed.
      Twenty-seven publications met the stated criteria for inclusion. There was a
      strong correlation between cancer risk and the size of the study, with small
      studies reporting much higher risks of cancer than larger studies. This
      association persisted when differences in the definition of BE, retrospective vs.
      prospective nature of the study, surveillance interval, and the effect of cancer
      detected in the first year were considered. The funnel diagram analysis suggested
      publication bias. CONCLUSIONS: The cancer risk in BE may be overestimated in the
      literature due to publication bias.

PMID- 10930369
TI  - Omeprazole, Helicobacter pylori status, and alterations in the intragastric
      milieu facilitating bacterial N-nitrosation.
AB  - BACKGROUND & AIMS: Omeprazole produces greater acid inhibition in Helicobacter
      pylori-positive than -negative subjects. We investigated whether this is
      accompanied by more profound changes in the intragastric milieu that facilitates
      bacterial synthesis of N-nitroso compounds. METHODS: Gastric juice pH; nitrite,
      ascorbic acid, and total vitamin C concentrations; and colonization by other
      bacteria were examined before and during omeprazole treatment in subjects with
      and without H. pylori infection. Studies were performed in the fasting state and
      after consumption of 2 mmol nitrate (equivalent to a salad meal). RESULTS: Before
      omeprazole, H. pylori-positive and -negative subjects were similar for all
      parameters. During omeprazole, H. pylori-positive subjects had a higher
      intragastric pH (7.8 vs. 3.0; P < 0.00001) and greater colonization with non-H.
      pylori species (5 x 10(7) vs. 5 x 10(5) CFU/mL; P < 0.05). These bacteria
      included nitrosating species. During omeprazole treatment, H. pylori-positive
      subjects had higher intragastric nitrite levels after the nitrate meal (median
      area under the concentration/time curve, 12,450 vs. 4708 micromol/L. min; P =
      0.04). Omeprazole lowered intragastric vitamin C levels in H. pylori-positive but
      not -negative subjects (1.8 vs. 3.4 microg/mL, respectively; P = 0.02).
      CONCLUSIONS: In H. pylori-positive subjects, omeprazole produces disturbances in
      intragastric nitrite, vitamin C, and bacterial colonization that facilitate
      bacterial N-nitrosation. This may place them at increased risk of mutagenesis and
      carcinogenesis.

PMID- 10930370
TI  - Neurotensin stimulates Cl(-) secretion in human colonic mucosa In vitro: role of
      adenosine.
AB  - BACKGROUND & AIMS: Previous studies indicated that the peptide neurotensin (NT)
      stimulates Cl(-) secretion in animal small intestinal mucosa in vitro. In this
      study, we investigated whether NT causes Cl(-) secretion in human colonic mucosa
      and examined the mechanism of this response. METHODS: Human mucosal preparations
      mounted in Ussing chambers were exposed to NT. Drugs for pharmacologic
      characterization of NT-induced responses were applied 30 minutes before NT.
      RESULTS: Serosal, but not luminal, administration of NT (10(-8) to 10(-6) mol/L)
      induced a rapid, monophasic, concentration- and chloride-dependent, bumetanide
      sensitive short-circuit current (Isc) increase that was inhibited by the specific
      nonpeptide NT receptor antagonists SR 48692 and SR 142948A, the neuronal blocker
      tetrodotoxin, and the prostaglandin synthesis inhibitor indomethacin. The mast
      cell stabilizer lodoxamide and the histamine 1 and 2 receptor antagonists
      pyrilamine and ranitidine, respectively, did not significantly alter NT-induced
      Isc increase. In contrast, the adenosine receptor 1 and 2 antagonists inhibited
      this secretory response, whereas the adenosine uptake inhibitors S-(4
      nitrobenzyl)-6-thioguanosine and S-(4-nitrobenzyl)-6-thioinosine and the
      adenosine deaminase inhibitor deoxycoformycin potentiated NT-induced Isc
      increase. Serosal adenosine induced a rapid, monophasic, concentration- and
      chloride-dependent, bumetanide-sensitive Isc increase. CONCLUSIONS: NT stimulates
      chloride secretion in human colon by a pathway(s) involving mucosal nerves,
      adenosine, and prostaglandins.

PMID- 10930371
TI  - Acid-dependent adherence of Helicobacter pylori urease to diverse
      polysaccharides.
AB  - BACKGROUND & AIMS: The significance of acid-primed recognition of ligands by
      Helicobacter pylori urease is unknown. This study aimed to further characterize
      the specificity of urease adherence in vitro and verify whether specific
      inhibition will translate into in vivo suppression of colonization. METHODS: A
      highly sensitive competitive enzyme-linked ligand capture assay was used to
      quantify the capacity of each test inhibitor to compete with labeled mucin for
      binding sites on immobilized native urease. A model polymer that strongly bound
      urease was used in an in vivo trial using euthymic hairless mice as an infection
      model. RESULTS: The blockage of urease-gastric mucin interaction by certain
      inhibitors revealed an acid-functional lectin-like activity by urease,
      specifically recognizing bacterial lipopolysaccharides and certain species of
      polysaccharides, nonbacterial glycolipids, and glycoproteins. Dextran sulfate
      significantly (P < 0.01) suppressed colonization of mice by H. pylori when given
      before and/or after challenge. CONCLUSIONS: The acid-driven high-affinity
      adherence of H. pylori urease to mucin and lipopolysaccharides contributes to
      gastric mucosal colonization by the bacterium based on in vivo targeting
      experiments using specific polysaccharides in a mouse model with acute infection.
      Acid-functional urease-homing polysaccharides that can interfere with urease
      mucin or H. pylori whole cell-mucin interaction in vitro can significantly
      interfere with colonization by the bacterium in vivo.

PMID- 10930372
TI  - Protective role of neurotrophins in experimental inflammation of the rat gut.
AB  - BACKGROUND & AIMS: Sensory neuropeptides modulate the mucosal response to
      inflammation in experimental colitis. Because nerve growth factor (NGF) regulates
      the expression of neuropeptides such as substance P and calcitonin gene-related
      peptide (CGRP) and is implicated as a link between the nervous system and the
      immune system in the inflammatory process, we investigated the functional role of
      NGF and neurotrophin-3 during experimental colitis. METHODS: Immunoneutralizing
      antibodies specific for NGF and neurotrophin (NT)-3 were used to block their
      endogenous activity. Mild trinitrobenzene sulfonic acid (TNBS) colitis was
      induced, and damage scores were assessed after 1 week. Neuropeptide content in
      the colon and NT messenger RNA (mRNA) expression were determined. RESULTS: The
      pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in
      the severity of the experimental inflammation as assessed by a macroscopic damage
      score, histologic ulceration score, and myeloperoxidase activity in the tissue.
      CGRP, but not substance P, contents in the colon were significantly reduced by
      NGF immunoneutralization. NGF mRNA was slightly up-regulated after NGF
      immunoneutralization, but NT-3 mRNA was unchanged by NT-3 immunoneutralization.
      CGRP mRNA was not significantly changed after 1 week of colitis by NGF or NT-3
      immunoneutralization, whereas beta-preprotachykinin mRNA was up-regulated after
      immunoneutralization. CONCLUSIONS: These findings suggest a regulatory role for
      NGF and NT-3 in experimental inflammation of the gut. This effect may be partly
      caused by the reduction of mucosal CGRP content caused by the NGF blockade.

PMID- 10930373
TI  - Central nervous system nitric oxide induces oropharyngeal swallowing and
      esophageal peristalsis in the cat.
AB  - BACKGROUND & AIMS: The functional role of brainstem nitric oxide (NO) in
      swallowing and esophageal peristalsis remains unknown. We examined the effects of
      blockade of central nervous system (CNS) NO synthase (NOS) on swallowing and on
      primary and secondary peristalsis. METHODS: (1) The effect of intravenous (IV)
      NOS inhibitor N(G)-nitro-L-arginine (L-NNA) on swallowing and swallowing-induced
      peristalsis was examined. (2) An NOS inhibitor (N(G)-monomethyl-L-arginine [L
      NMMA]) was administered into the fourth ventricle intracerebroventricularly
      (ICV), and its effects on swallowing and primary and secondary peristalsis were
      examined. RESULTS: (1) IV L-NNA significantly reduced the number of oropharyngeal
      swallows and the induction of primary peristalsis in the smooth muscle portion of
      the esophageal body; the change was not significant within the striated muscle
      portion. (2) L-NMMA given ICV significantly reduced the number of oropharyngeal
      swallows and the incidence of primary peristalsis in both smooth and striated
      muscle, but the reduction in amplitude was significant only for the smooth muscle
      contraction. There was a significant reduction in both the amplitude and
      incidence of secondary peristalsis, only in the smooth muscle portion.
      CONCLUSIONS: CNS NO is an important neurotransmitter in the induction of
      oropharyngeal swallowing and esophageal peristalsis. The neural substrates
      mediating striated and smooth muscle peristalsis may be both anatomically and
      neurochemically distinct.

PMID- 10930374
TI  - Quantitative analysis of intestinal motor patterns: spatiotemporal organization
      of nonneural pacemaker sites in the rat ileum.
AB  - BACKGROUND & AIMS: Intestinal contractions are triggered by electric activity of
      pacemaker cells within the smooth muscle. However, the precise spatial
      organization of the pacemaker system is unknown. We directly assessed the
      spatiotemporal organization of pacemakers by video image analysis combined with
      manometry and electromyography. METHODS: Isolated segments of rat ileum were
      perfused arterially with oxygenated fluorocarbon solution and luminally with
      saline. Luminal end pressures, extracellular electric activity, and images of the
      intestine were recorded simultaneously. Tetrodotoxin, N(G)-nitro-L-arginine
      methyl ester (L-NAME), L-arginine, and eserine were administered arterially.
      RESULTS: Myogenic contractions originated in discrete areas (dominant pacemakers)
      and propagated faster in aboral than in oral direction. Dominant pacemakers were
      distributed along the intestine at regular intervals. The preparations were
      mostly driven by 1 pacemaker at the time, but 2 or 3 pacemakers with different
      frequencies could be active simultaneously. Tetrodotoxin decreased aboral
      propagation velocity and revealed multiple regularly spaced pacemaker areas.
      Eserine increased, whereas L-arginine decreased, their frequency. After L-NAME,
      pacemaker activity increased and isolated pacemakers with higher frequency
      appeared. CONCLUSIONS: Nonneural pacemakers in rat ileum are functionally
      organized not as a continuous system but show a segmental arrangement, spatially
      and temporally modulated by neural activity.

PMID- 10930375
TI  - Identification and characterization of a novel gastric peptide hormone: the
      motilin-related peptide.
AB  - BACKGROUND & AIMS: This study looked for new proteins with expression restricted
      to the gastric epithelium that may provide insight to the differentiation and
      function of the gastric unit. METHODS: A novel complementary DNA was isolated and
      sequenced, and its expression was examined in mouse tissues at both messenger RNA
      and protein levels. Subcellular localization was studied using immunoelectron
      microscopy. The posttraductional processing of the protein was analyzed in vitro
      by protein microsequencing and in vivo by Western blotting. RESULTS: We
      identified a novel protein that is mainly expressed by the secretory granules of
      the stomach enteroendocrine cells. This protein has sequence similarity with
      prepromotilin, the precursor of the motilin hormone and the motilin-associated
      peptide. As for the prepromotilin, a posttraductional maturation leads to a
      secreted peptide that is further cleaved at a dibasic site and gives rise to the
      motilin-related peptide (MTLRP) and MTLRP-associated peptide. CONCLUSIONS: We
      have identified and characterized a novel gene encoding the preproMTLRP protein.
      MTLRP presents similarity to motilin and is specifically expressed by
      enteroendocrine cells of the stomach and therefore represents a novel hormone.

PMID- 10930376
TI  - Role of Na(+)HCO(3)(-) cotransporter NBC1, Na(+)/H(+) exchanger NHE1, and
      carbonic anhydrase in rabbit duodenal bicarbonate secretion.
AB  - BACKGROUND & AIMS: HCO(3)(-) supply to the enterocyte is rate limiting for
      duodenal HCO(3)(-) secretion (J(HCO3-)). This study defines the molecular nature
      of the major HCO(3)(-) uptake pathways in rabbit duodenocytes and investigates
      their physiologic significance and regulation during basal and stimulated J(HCO3
      ). METHODS & RESULTS: pH gradient-driven (22)Na(+) uptake into duodenal
      basolateral membrane vesicles was partly HCO(3)(-) dependent, stilbene sensitive,
      and therefore mediated by Na(+)HCO(3)(-) cotransport, and partly HCO(3)(-)
      independent, Hoechst 642 sensitive, and therefore mediated by the Na(+)/H(+)
      exchanger isoform NHE1. Semiquantitative polymerase chain reaction (PCR) revealed
      high duodenal expression levels for the NBC1 isoform of the Na(+)HCO(3)(-)
      cotransporter gene family and NHE1. Cloning and comparison of full-length rabbit
      with human gastrointestinal and kidney NBC1 subtype revealed a conserved protein
      kinase A consensus sequence in the cytoplasmic N-terminus of the gastrointestinal
      NBC1. Inhibition of either Na(+)HCO(3)(-) cotransport or carbonic anhydrase
      reduced ouabain-sensitive J(HCO3-) in in vitro rabbit duodenal mucosae by
      approximately 50%, but did not affect 8-Br-cAMP-induced DeltaJ(HCO3-), suggesting
      cAMP-mediated up-regulation of the alternative pathway. However, inhibition of
      both Na(+)HCO(3)(-) cotransport and either carbonic anhydrase or NHE1 strongly
      reduced DeltaJ(HCO3-). CONCLUSIONS: NBC1 and NHE1 are the major base importers in
      rabbit duodenocytes. Na(+)HCO(3)(-) cotransport and CO(2) hydration/Na(+)/H(+)
      exchange are equally important pathways for duodenal HCO(3)(-) supply and are up
      regulated during cAMP-mediated stimulation.

PMID- 10930377
TI  - Gastrointestinal glutathione peroxidase prevents transport of lipid
      hydroperoxides in CaCo-2 cells.
AB  - BACKGROUND & AIMS: Gastrointestinal glutathione peroxidase (GI-GPx), 1 of the 4
      types of selenium-dependent glutathione peroxidases, is expressed exclusively in
      the gastrointestinal system and has therefore been suggested to function as a
      barrier against the absorption of dietary hydroperoxides. METHODS: The selenium
      dependent expression of GI-GPx and cytosolic GPx (cGPx) was analyzed by Western
      blotting. Transport of 13-hydroperoxy octadecadienoic acid (13-HPODE) was
      investigated in a CaCo-2 cell monolayer modulated in GI-GPx and cGPx by selenium
      restriction or repletion. Localization of GI-GPx in rat intestine was visualized
      by immunohistochemistry. RESULTS: Low but significant GI-GPx levels were detected
      in selenium-deficient CaCo-2 cells and in the gastrointestinal tract of selenium
      deficient rats, whereas cGPx was completely absent. Selenium supplementation of
      CaCo-2 cells resulted in a 5-fold increase of GI-GPx protein, whereas total GPx
      activity increased by a factor of 13, with most of the GPx activity under
      selenium-adequate conditions being cGPx. Irrespective of the selenium status, 13
      HPODE did not reach the basolateral side of an intact CaCo-2 cell monolayer.
      Depending on the selenium status, hydroperoxides damaged the monolayer as
      evidenced by loss of transepithelial resistance and paracellular diffusion of
      lucifer yellow. Only under these conditions was unmetabolized 13-HPODE detectable
      at the basolateral side. CONCLUSIONS: Low GI-GPx levels, as present in selenium
      deficiency, suffice to prevent transport of 13-HPODE. GI-GPx may thus function as
      a barrier against hydroperoxide absorption. cGPx contributes to balance major
      oxidative challenge.

PMID- 10930378
TI  - Chromosomal changes and clonality relationship between primary and recurrent
      hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is highly malignant and prone
      to recur after surgical treatment. Differentiation between a true relapse of HCC
      and a second primary tumor is of clinical importance. However, no convenient
      method is currently available. METHODS: Comparative genomic hybridization (CGH)
      was used to analyze 31 pairs of initial and recurrent HCC samples obtained from
      patients undergoing 2 consecutive surgeries. The resulting chromosomal aberration
      profiles were used as genomic fingerprints to determine tumor clonalities and
      their relationships. RESULTS: Eleven recurrent tumors with high clonal
      relationship (CR) values (>0.95) were found to be relapsed HCCs, and 11 tumors
      with CR values close to 0 were found to be second primary HCCs. The other 9
      paired samples had inconclusive CR values between 0.95 and 0.4. Two were
      confirmed by hepatitis B virus integration and X chromosome inactivation analysis
      to be de novo cancers (CR values, 0.35 and 0. 23, respectively). Initial HCCs
      that subsequently relapsed accumulated more chromosomal aberration events than
      those that developed de novo HCC (mean, 16.1 +/- 4.5 vs. 5.4 +/- 4.8 events; P <
      0.01). Also, they more frequently showed gains on chromosome arms 3q, 6p, 8q, and
      17q and losses on 4q and 16p. CONCLUSIONS: CGH is useful for chromosomal
      aberration study and tumor clonality analysis. More and characteristic genomic
      changes in the initial HCC suggest that subsequent tumor recurrence is a true
      relapse.

PMID- 10930379
TI  - Two novel nonsense mutations of HFE gene in five unrelated italian patients with
      hemochromatosis.
AB  - BACKGROUND & AIMS: Most hemochromatosis patients of Northern European descent are
      homozygous for the C282Y mutation of HFE gene. In Italy, many patients with iron
      overload are not homozygous for C282Y, and the presence of other mutations or
      other genetic determinant has been suggested. METHODS: Five unrelated Italian
      patients heterozygous for C282Y with the classic hemochromatosis phenotype were
      studied. The entire coding sequence and the exon-intron boundaries of the HFE
      gene were analyzed. Chromosome 6p haplotypes were defined in each patient by
      analysis of D6S265, D6S105, and D6S1281 microsatellites. RESULTS: Two novel
      nonsense HFE mutations were identified in exon 3 in the C282Y negative
      chromosome. The first one, a G-to-T transition at codon 168, was detected in 3
      probands; the second, a G-to-A transition at codon 169, was detected in the
      others. CONCLUSIONS: The 2 nonsense mutations in the compound heterozygous state
      with C282Y result in the classic hemochromatosis phenotype in several unrelated
      Italian patients. This confirms that hemochromatosis in Italy is not as
      homogeneous as in northern Europe and suggests that other mutations can exist in
      C282Y or H63D heterozygotes with iron overload. These findings have practical
      implications for diagnostic and screening strategies for hemochromatosis.

PMID- 10930380
TI  - Tumor necrosis factor alpha in the pathogenesis of human and murine fulminant
      hepatic failure.
AB  - BACKGROUND & AIMS: The tumor necrosis factor (TNF)-alpha/TNF receptor system is
      critical for liver development because hepatocytes undergo apoptosis if the
      antiapoptotic cascades resulting in RelA NF-kappaB activation are not effective.
      Therefore, we studied the role of TNF-alpha in fulminant hepatic failure (FHF)
      and developed a new therapeutic strategy. METHODS: Serum levels and hepatic
      expression of TNF-alpha and both TNF receptors were determined by enzyme-linked
      immunosorbent assay and immunohistochemistry. Adenoviral vectors were constructed
      expressing dominant-negative proteins interfering with intracellular TNF-alpha
      dependent pathways. The relevance of these constructs was studied in primary
      mouse hepatocytes and in a murine model of FHF. RESULTS: Serum levels of TNF
      alpha and TNF receptors are significantly increased in FHF; this increase
      correlates with patient prognosis. In livers of patients with FHF, infiltrating
      mononuclear cells express high amounts of TNF-alpha and hepatocytes overexpress
      TNF receptor 1 (TNF-R1). Apoptotic hepatocytes are significantly increased in
      FHF, and there is a strong correlation with TNF-alpha expression, which is even
      more pronounced in areas of mononuclear infiltrates. In an in vivo FHF model, the
      Fas-associated death domain (FADD), adenovirus selectively blocked the
      intracellular pathway, leading to mitochondrial cytochrome c release, caspase-3
      activation, and, thus, apoptosis of hepatocytes. CONCLUSIONS: The results show
      that the TNF-alpha/TNF-R1 system is involved in the pathogenesis of FHF in
      humans. Studies in this animal model indicate that FADD may serve as a molecular
      target to prevent liver cell death in vivo.

PMID- 10930381
TI  - Chronic pancreatitis associated with an activation peptide mutation that
      facilitates trypsin activation.
AB  - BACKGROUND & AIMS: Mutations of the cationic trypsinogen have been described in
      hereditary pancreatitis. We report a new trypsinogen mutation in the activation
      peptide of the proenzyme in a family with chronic pancreatitis. METHODS: The
      coding region of the cationic trypsinogen gene was sequenced after polymerase
      chain reaction amplification. The following peptides homologous to the N-terminal
      end of cationic trypsinogen were synthesized (one-letter code, mutated amino acid
      underlined): wild-type peptide, APFDDDDKIVGG; pD22G, APFDDDGKIVGG; pK23R,
      APFDDDDRIVGG. The sequences of pD22G and pK23R correspond to the recently
      identified mutation K23R and to the mutation described here (D22G). To mimic
      trypsinogen activation, these peptides were digested with trypsin for 30 minutes
      at pH 5.0-8. 0, and the fragments were analyzed by high-performance liquid
      chromatography. RESULTS: In a family with clinical evidence of hereditary chronic
      pancreatitis, a missense mutation of codon 22 (GAC-->GGC) of the cationic
      trypsinogen was found. This mutation results in a substitution of aspartic acid
      by glycine; therefore, the mutation was called D22G. Chromatographic analysis of
      tryptic digests of the peptides pD22G and pK23R showed hydrolysis rates of 22%
      and 75%, respectively, whereas the wild-type peptide was hydrolyzed at only 6%.
      The cleavage rates were reduced at lower pH, and no hydrolysis occurred without
      trypsin. CONCLUSIONS: The activation peptides of the trypsinogen variants D22G
      and K23R could be released at a higher rate than in wild-type trypsinogen,
      resulting in increased amounts of trypsin in the pancreas, which could initiate
      pancreatitis.

PMID- 10930382
TI  - Ligands of peroxisome proliferator-activated receptor gamma modulate
      profibrogenic and proinflammatory actions in hepatic stellate cells.
AB  - BACKGROUND & AIMS: Proliferation and migration of hepatic stellate cells (HSCs)
      and expression of chemokines are involved in the pathogenesis of liver
      inflammation and fibrogenesis. Peroxisome proliferator-activated receptor (PPAR)
      gamma is a receptor transcription factor that controls growth and differentiation
      in different tissues. We explored the effects of PPAR-gamma agonists on the
      biological actions of cultured human HSCs. METHODS: HSCs were isolated from
      normal human liver tissue and used in their myofibroblast-like phenotype or
      immediately after isolation. Activation of PPAR-gamma was induced with 15-deoxy
      Delta(12, 14)-prostaglandin J(2) or with troglitazone. RESULTS: PPAR-gamma
      agonists dose-dependently inhibited HSC proliferation and chemotaxis induced by
      platelet-derived growth factor. This effect was independent of changes in
      postreceptor signaling or expression of c-fos and c-myc and was associated with
      inhibition of cell cycle progression beyond the G(1) phase. Activation of PPAR
      gamma also resulted in a complete inhibition of the expression of monocyte
      chemotactic protein 1 at the gene and protein levels. Comparison of quiescent and
      culture-activated HSCs revealed a marked decrease in PPAR-gamma expression in
      activated cells. CONCLUSIONS: Activation of PPAR-gamma modulates profibrogenic
      and proinflammatory actions in HSCs. Reduced PPAR-gamma expression may contribute
      to confer an activated phenotype to HSCs.

PMID- 10930383
TI  - Nitrovasodilators inhibit platelet-derived growth factor-induced proliferation
      and migration of activated human hepatic stellate cells.
AB  - BACKGROUND & AIMS: Nitrovasodilators have been proposed for the treatment of
      portal hypertension alone or in combination with beta-blockers. In addition to
      their vasodilatory properties, nitric oxide (NO) donors may exert direct
      antifibrogenic properties. We evaluated the effect of nitroglycerin (NTG) and S
      nitroso-N-acetyl penicillamine (SNAP) on the mitogenic and chemotactic properties
      of platelet-derived growth factor (PDGF)-BB and the modulation of the relative
      intracellular signaling pathways in fully activated human hepatic stellate cells
      (HSCs), a cell type that plays an active role in liver fibrogenesis and portal
      hypertension. METHODS & RESULTS: Both NTG and SNAP induced a dose-dependent
      decrease in PDGF-induced DNA synthesis and cell migration, which was associated
      with a decrease in PDGF-induced intracellular Ca(2+) increase and extracellular
      signal-regulated kinase (ERK) activity. These effects were not related to
      activation of the classic soluble guanylate cyclase (sGC)/guanosine 3',5'-cyclic
      monophosphate pathway; accordingly, Western blot analysis of HSC lysates revealed
      the absence of the alpha(1)beta(1) ubiquitous subunits of sGC, whereas they were
      detectable in quiescent HSCs, freshly isolated from normal human liver.
      Conversely, both NTG and SNAP induced a more than 10-20-fold increase in
      prostaglandin E(2) in cell supernatants within 1 minute, associated with an
      increase in intracellular adenosine 3',5'-cyclic monophosphate levels.
      Accordingly, the inhibitory effects of NO donors on PDGF action and signaling
      were eliminated after preincubation with ibuprofen. CONCLUSIONS: These results
      suggest that NO donors may exert a direct antifibrogenic action by inhibiting
      proliferation, motility, and contractility of HSCs in addition to a reduction of
      fibrillar extracellular matrix accumulation.

PMID- 10930384
TI  - Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer
      binding proteins.
AB  - BACKGROUND & AIMS: Expression of cyclooxygenase (COX)-2 in response to
      lipopolysaccharide (LPS) challenge has been analyzed in cultured fetal, neonatal,
      and adult hepatocytes and in hepatoma cell lines. METHODS: To study the
      mechanisms of LPS-dependent expression of COX-2 in these cells, the activity of
      the COX-2 promoter and the levels of CCAAT/enhancer-binding proteins (C/EBPs)
      were determined. RESULTS: COX-2 was induced in fetal hepatocytes, but this
      response declined rapidly after birth. This loss of inducibility of COX-2
      paralleled the expression of C/EBP-alpha in neonatal hepatocytes. Transfection of
      fetal and adult hepatocytes with sequences corresponding to the 5'-flanking
      region of the rat COX-2 gene confirmed the absence of promoter activity in adult
      hepatocytes. Moreover, transient expression of C/EBP-alpha, but not C/EBP-delta,
      in the hepatoma cell line AT3F cells abolished the COX-2 promoter activity.
      Prolonged culture of adult hepatocytes restored the induction of COX-2 after
      complete disappearance of C/EBP-alpha. CONCLUSIONS: These results suggest that
      the presence of high levels of C/EBP-alpha is involved in the impairment of COX-2
      expression in adult hepatocytes challenged with proinflammatory stimuli.

PMID- 10930385
TI  - A patient with improvement of ulcerative colitis after appendectomy.
AB  - Recently, several retrospective studies have shown an inverse association between
      appendectomy and development of ulcerative colitis. We describe a 21-year-old man
      with distal ulcerative colitis and appendiceal involvement. The patient passed
      bloody stools continually during the 3 years before admission. Macroscopic and
      microscopic findings showed chronic moderate inflammation of the appendix and
      rectum. The ratio of CD4 to CD8 lymphocytes isolated from rectal and appendiceal
      mucosa was increased (4.3 and 3.8, respectively) compared with controls (n = 11;
      1.0 in the rectum and 1.4 in the appendix). Clinical symptoms and colonoscopic
      and microscopic findings improved significantly after appendectomy. In addition,
      the amount of interferon gamma secreted from rectal lymphocytes was reduced to 89
      pg/mL after surgery (before appendectomy, 254 pg/mL). However, interleukin 4
      production was below detectable levels both before and after appendectomy. These
      findings suggest that appendectomy resulted in altered T-helper (Th)1/Th2 balance
      in this patient. In the 3 years since surgery, the patient has been in good
      condition without recurrence of symptoms. This is the first report demonstrating
      therapeutic benefit of appendectomy in a patient with ulcerative colitis and
      potential mechanistic relationship.

PMID- 10930386
TI  - Covert transmission of hepatitis C virus during bloody fisticuffs.
AB  - Hepatitis C virus (HCV) is transmitted primarily through direct percutaneous
      exposure to infected blood. Sporadic HCV cases exist and may represent more than
      10% of HCV transmission. We report the first case of documented transmission of
      HCV during a fight from a person who unknowingly had chronic HCV infection to a
      person who subsequently contracted acute hepatitis C. Patient-to-patient
      transmission was ascertained by sequence analysis of part of the NS5B genome and
      phylogenetic analysis. This case report suggests that sporadic HCV infection may
      be a result of blood exposure. This example of transmission could have a major
      impact in sports such as boxing or rugby. We suggest that in any fight, single
      use or nondisposable material should be used to dry blood to avoid such
      contamination.

PMID- 10930387
TI  - Nitric oxide in mucosal defense: a little goes a long way.
AB  - Nitric oxide (NO) is now recognized as an important modulator of an enormous
      number of physiological processes, ranging from blood pressure regulation to
      neuronal transmission to penile erectile function. In the gastrointestinal tract,
      NO also participates in many physiological and pathophysiological processes. In
      this review, we summarize the contribution made by NO to the ability of the
      gastrointestinal mucosa to resist injury induced by luminal toxins and to defend
      against microbial invasion. We also review some of the main features of NO
      chemistry and the potential of NO as a target for new drugs to treat
      gastrointestinal disorders.

PMID- 10930388
TI  - Nonsteroidal anti-inflammatory drug gastropathy.
AB  - By inhibiting prostaglandin synthesis, nonsteroidal anti-inflammatory drugs
      (NSAIDs) compromise gastroduodenal defense mechanism including blood flow and
      mucus/bicarbonate secretion. This has led to NSAIDs being the most widely
      reported drug cause of adverse events. While NSAIDs also cause dyspepsia,
      inhibition of prostaglandin synthesis may reduce this from even higher levels
      that would otherwise prevail and mask ulcer-related dyspepsia, making
      anticipatory management difficult. On average, the risk of ulcer complications
      increases 4-fold, resulting in 1.25 additional hospitalizations per 100 patient
      years according to one estimate. Older patients, those with a past history, and
      those taking anticoagulants or corticosteroids are at higher risk. Risk is dose
      dependent and is lower with ibuprofen at low doses than with other NSAIDs. It is
      unlikely that Helicobacter pylori increases the risk, and under some
      circumstances it may be protective. Selective inhibitors of the inducible
      cyclooxygenase 2 spare gastric mucosal prostaglandin synthesis and do not damage
      the gastric mucosa. Their place in therapy, compared with use of misoprostol or
      proton pump inhibitors, is currently emerging. Future competitors may include
      nitric oxide-donating, zwitterionic, or R-enantiomer NSAIDs.

PMID- 10930389
TI  - Biological clocks and the digestive system.
AB  - Circadian rhythms play a major role in regulating the digestive systems of many
      organisms. Cell proliferation, migration, differentiation, and even structure
      vary as a function of time of day in many different digestive organs (i.e.,
      stomach, gut, liver, and pancreas) and cell types, resulting in regionally
      specific temporal variations in protein and gene expression. Feeding and light
      set the hands of the digestive clock(s). However, the clockwork has a genetic
      basis. During the last 10 years, new developments have emerged in our
      understanding of how cells keep time. Surprisingly, clock genes in mammals are
      expressed not only in specialized time keepers in the brain, but also in
      peripheral organs, suggesting that the ability to keep time may also belong to
      cells within the digestive system. This article reviews several classic examples
      of circadian variation in the digestive system, with an emphasis on rhythms in
      cell proliferation, function, and structure. It also briefly summarizes several
      new ideas about how cells in the brain and possibly the digestive system keep
      time.

PMID- 10930390
TI  - List of available training programs.

PMID- 10930391
TI  - What to choose for diagnosis of bleeding colonic angiomas: colonoscopy,
      angiography, or helical computed tomography angiography?

PMID- 10930393
TI  - Barrett's esophagus: an overrated cancer risk factor.

PMID- 10930392
TI  - Probiotics in chronic pouchitis: restoring luminal microbial balance.

PMID- 10930394
TI  - Diet and colon cancer: strike out the bran

PMID- 10930395
TI  - A novel development in oral rehydration therapy

PMID- 10930396
TI  - Getting fat in the ICU.

PMID- 10930397
TI  - Fast facts-coeliac disease

PMID- 10930398
TI  - Active aminoacyl-tRNA synthetases are present in nuclei as a high molecular
      weight multienzyme complex.
AB  - Recent studies suggest that aminoacylation of tRNA may play an important role in
      the transport of these molecules from the nucleus to the cytoplasm. However,
      there is almost no information regarding the status of active aminoacyl-tRNA
      synthetases within the nuclei of eukaryotic cells. Here we show that at least 13
      active aminoacyl-tRNA synthetases are present in purified nuclei of both Chinese
      hamster ovary and rabbit kidney cells, although their steady-state levels
      represent only a small percentage of those found in the cytoplasm. Most
      interestingly, all the nuclear aminoacyl-tRNA synthetases examined can be
      isolated as part of a multienzyme complex that is more stable, and consequently
      larger, than the comparable complex isolated from the cytoplasm. These data
      directly demonstrate the presence of active aminoacyl-tRNA synthetases in
      mammalian cell nuclei. Moreover, their unexpected structural organization raises
      important questions about the functional significance of these multienzyme
      complexes and whether they might play a more direct role in nuclear to
      cytoplasmic transport of tRNAs.

PMID- 10930399
TI  - Matrix metalloproteinases collagenase-2, macrophage elastase, collagenase-3, and
      membrane type 1-matrix metalloproteinase impair clotting by degradation of
      fibrinogen and factor XII.
AB  - The effects of plasma proteins on controlling the activity of matrix
      metalloproteinases (MMPs, matrixins) have been the focus of numerous studies,
      although only a few have examined the influence of matrixins on plasma proteins.
      Recently, it has been shown that MMPs may play a role in the degradation of
      fibrin. We have now investigated the role of collagenase-2 (MMP-8), macrophage
      elastase (MMP-12), collagenase-3 (MMP-13), and membrane type 1-matrix
      metalloproteinase (MT1-MMP, MMP-14) in the degradation of fibrinogen and Factor
      XII of the plasma clotting system. Our data demonstrate that the catalytic
      domains of MMP-8, MMP-12, MMP-13, and MMP-14 can proteolytically process
      fibrinogen and, with the exception of MMP-8, also inactivate Factor XII (Hageman
      factor). We have identified the amino termini of the major protein fragments.
      Cleavage of fibrinogen occurred in all chains and resulted in significantly
      impaired clotting. Moreover, rapid proteolytic inactivation of Factor XII
      (Hageman factor) by MMP-12, MMP-13, and MMP-14 was noted. These results support
      the hypothesis of an impaired thrombolytic potential of MMP-degraded Factor XII
      in vivo. MMP-induced degradation of fibrinogen supports a plasmin-independent
      fibrinolysis mechanism. Consequently, degradation of these proteins may be
      important in inflammation, atherosclerosis, and angiogenesis, all of which are
      known to be influenced by MMP activity.

PMID- 10930401
TI  - Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells.
AB  - Cyclooxygenase-2 (COX-2) is not normally expressed in the human large intestine,
      but its levels are increased in the majority of human colorectal carcinomas. Here
      we investigate the regulation of constitutive COX-2 expression and prostaglandin
      production in human colorectal carcinoma cells. Both COX-2 mRNA and protein were
      expressed in well differentiated HCA-7, Moser, LS-174, and HT-29 cells, albeit at
      different levels. COX-2 expression was not detected in several poorly
      differentiated colon cancer cell lines including DLD-1. Transcriptional
      regulation played a key role for the expression of COX-2 in human colon carcinoma
      cells, and both the nuclear factor for interleukin-6 regulatory element and the
      cAMP-response element were responsible for regulation of COX-2 transcription. COX
      2 mRNA was more stable in HCA-7 cells than in the other cell lines tested. Both
      transcriptional and post-transcriptional regulation of COX-2 involved the MAP
      kinase pathway. Modulation of the Akt/protein kinase B or Rho B signaling
      pathways altered the levels of COX-2 expression. Furthermore, COX-2 protein is
      degraded through ubiquitin proteolysis, and its half-life was approximately 3.5-8
      h. HCA-7 cells produced significant quantities of prostaglandin E(2) and other
      prostaglandins. Moser and LS-174 cells also generated prostaglandins, but levels
      were significantly lower than that observed in HCA-7 cells.

PMID- 10930400
TI  - Suppression of rat thromboxane synthase gene transcription by peroxisome
      proliferator-activated receptor gamma in macrophages via an interaction with
      NRF2.
AB  - We have studied the transcription regulation of the rat thromboxane synthase
      (TXS) gene by peroxisome proliferator-activated receptor gamma (PPARgamma) in
      macrophages. The transcription activity of a cloned 5'-flanking region (1.6
      kilobases) of the rat TXS gene (5'FL-TXS) was examined by luciferase reporter
      gene assay. TXS mRNA expression and the transcription activity of 5'FL-TXS were
      inhibited by PPARgamma ligands, 15-deoxy-Delta(12,14)-prostaglandin J(2)
      (PGJ(2)), and the thiazolidinedione troglitazone (TRO) in a dose-dependent
      manner. Overexpression of PPARgamma also significantly suppressed transcription,
      and further addition of PGJ(2) or TRO augmented the suppression. Deletion
      analysis showed that the element responsible for the PPARgamma effect is located
      in a region containing the nuclear factor E2 (NF-E2)/AP-1 site (-98/-88), which
      was indicated to be the major promoter of the TXS gene. By electrophoretic
      mobility shift assay using the NF-E2/AP-1 site and nuclear extracts from
      macrophages, we observed a specific protein-DNA complex formation, which was
      inhibited by a specific antibody against the transcription factor NRF2 (NF-E2
      related factor 2). Moreover, the complex was decreased with PGJ(2), TRO, or in
      vitro translated PPARgamma. The transcription suppression by PPARgamma was
      confirmed using this truncated NRF2-binding element (-98/-88) by the reporter
      gene assay. Finally, a direct interaction between PPARgamma and NRF2 was
      confirmed by glutathione S-transferase pull-down assay. In conclusion, the NRF2
      binding site (-98/-88) is the major promoter of 5'FL-TXS which can be suppressed
      by activated PPARgamma via a protein-protein interaction with NRF2 in
      macrophages.

PMID- 10930402
TI  - LcrV, a substrate for Yersinia enterocolitica type III secretion, is required for
      toxin targeting into the cytosol of HeLa cells.
AB  - Pathogenic Yersinia species employ type III machines to transport virulence
      factors across the bacterial envelope. Some substrates for the type III machinery
      are secreted into the extracellular medium, whereas others are targeted into the
      cytosol of host cells. We found that during infection of tissue culture cells,
      yersiniae secrete small amounts of LcrV into the extracellular medium. Knockout
      mutations of lcrV abolish Yersinia targeting and reduce expression of the
      lcrGVHyopBD operon. In contrast, a block in LcrV secretion does not affect
      targeting, but results in premature expression and secretion of Yop proteins into
      the extracellular medium. LcrV-mediated activation of the type III pathway is
      thought to occur by sequestration of the regulatory factor LcrG, presumably via
      the formation of LcrV.LcrG complexes. These results suggest that intrabacterial
      LcrV regulates the expression and targeting of Yop proteins during Yersinia
      infection, whereas secreted LcrV is required to ensure specificity of Yop
      injection into eukaryotic cells.

PMID- 10930403
TI  - Changes of matrilin forms during endochondral ossification. Molecular basis of
      oligomeric assembly.
AB  - To understand the molecular properties of matrilin-3, a newly discovered member
      of the novel extracellular matrix protein family, we cloned a MAT-3 cDNA from
      developing chicken sterna. Real time quantitative reverse-transcription
      polymerase chain reaction indicates that MAT-3 mRNA is mainly expressed in the
      proliferation zone of a growth plate. It is also expressed in the maturation
      zone, overlapping with that of the mature chondrocyte-abundant matrilin-1 mRNA.
      This suggests that matrilin-3 may self-assemble in the proliferation zone, in
      addition to its co-assembly with matrilin-1 during endochondral ossification.
      Transfection of a MAT-3 cDNA into COS-7 cells shows that MAT-3 predominantly
      forms a homotetramer but also a trimer and a dimer. Co-transfection of both MAT-3
      and MAT-1 cDNAs results in three major matrilins as follows: (MAT-1)(3), (MAT
      3)(4), and (MAT-1)(2)(MAT-3)(2). Thus matrilin-3 may assemble into both homotypic
      and heterotypic oligomers. Our analysis shows that the assembly of MAT-3 does not
      depend on the number of epidermal growth factor repeats within the molecule, but
      the presence of Cys(412) and Cys(414) within the coiled-coil domain, which form
      covalent disulfide linkage responsible for both homo-oligomerization of MAT-3 and
      hetero-oligomerization of MAT-3 and MAT-1. Our data suggest that the varying
      synthetic levels of matrilins in different zones of a growth plate may result in
      a change of matrilin oligomeric forms during endochondral ossification.

PMID- 10930404
TI  - Distinct roles of the second and third cytoplasmic loops of bovine rhodopsin in G
      protein activation.
AB  - In contrast to the extensive studies of light-induced conformational changes in
      rhodopsin, the cytoplasmic architecture of rhodopsin related to the G protein
      activation and the selective recognition of G protein subtype is still unclear.
      Here, we prepared a set of bovine rhodopsin mutants whose cytoplasmic loops were
      replaced by those of other ligand-binding receptors, and we compared their
      ability for G protein activation in order to obtain a clue to the roles of the
      second and third cytoplasmic loops of rhodopsin. The mutants bearing the third
      loop of four other G(o)-coupled receptors belonging to the rhodopsin superfamily
      showed significant G(o) activation, indicating that the third loop of rhodopsin
      possibly has a putative site(s) related to the interaction of G protein and that
      it is simply exchangeable with those of other G(o)-coupled receptors. The mutants
      bearing the second loop of other receptors, however, had little ability for G
      protein activation, suggesting that the second loop of rhodopsin contains a
      specific region essential for rhodopsin to be a G protein-activating form.
      Systematic chimeric and point mutational studies indicate that three amino acids
      (Glu(134), Val(138), and Cys(140)) in the N-terminal region of the second loop of
      rhodopsin are crucial for efficient G protein activation. These results suggest
      that the second and third cytoplasmic loops of bovine rhodopsin have distinct
      roles in G protein activation and subtype specificity.

PMID- 10930405
TI  - Differential regulation of the catalytic and accessory subunit genes of
      Drosophila mitochondrial DNA polymerase.
AB  - The developmental pattern of expression of the genes encoding the catalytic
      (alpha) and accessory (beta) subunits of mitochondrial DNA polymerase (pol gamma)
      has been examined in Drosophila melanogaster. The steady-state level of pol gamma
      beta mRNA increases during the first hours of development, reaching its maximum
      value at the start of mtDNA replication in Drosophila embryos. In contrast, the
      steady-state level of pol gamma-alpha mRNA decreases as development proceeds and
      is low in stages of active mtDNA replication. This difference in mRNA abundance
      results at least in part from differences in the rates of mRNA synthesis. The pol
      gamma genes are located in a compact cluster of five genes that contains three
      promoter regions (P1-P3). The P1 region directs divergent transcription of the
      pol gamma-beta gene and the adjacent rpII33 gene. P1 contains a DNA replication
      related element (DRE) that is essential for pol gamma-beta promoter activity, but
      not for rpII33 promoter activity in Schneider's cells. A second divergent
      promoter region (P2) controls the expression of the orc5 and sop2 genes. The P2
      region contains two DREs that are essential for orc5 promoter activity, but not
      for sop2 promoter activity. The expression of the pol gamma-alpha gene is
      directed by P3, a weak promoter that does not contain DREs. Electrophoretic
      mobility shift experiments demonstrate that the DRE-binding factor (DREF)
      regulatory protein binds to the DREs in P1 and P2. DREF regulates the expression
      of several genes encoding key factors involved in nuclear DNA replication. Its
      role in controlling the expression of the pol gamma-beta and orc5 genes
      establishes a common regulatory mechanism linking nuclear and mitochondrial DNA
      replication. Overall, our results suggest that the accessory subunit of mtDNA
      polymerase plays an important role in the control of mtDNA replication in
      Drosophila.

PMID- 10930406
TI  - Identification of a novel inhibitor specific to the fungal chitin synthase.
      Inhibition of chitin synthase 1 arrests the cell growth, but inhibition of chitin
      synthase 1 and 2 is lethal in the pathogenic fungus Candida albicans.
AB  - As in Saccharomyces cerevisiae, the pathogenic fungus Candida albicans harbors
      three chitin synthases called CaChs1p, CaChs2p, and CaChs3p, which are
      structurally and functionally analogous to the S. cerevisiae ScChs2p, ScChs1p,
      and ScChs3p, respectively. In S. cerevisiae, ScCHS1, ScCHS2, and ScCHS3 are all
      non-essential genes; only the simultaneous disruption of ScCHS2 and ScCHS3 is
      lethal. The fact that a null mutation of the CaCHS1 is impossible, however,
      implies that CaCHS1 is required for the viability of C. albicans. To gain more
      insight into the physiological importance of CaCHS1, we identified and
      characterized a novel inhibitor that was highly specific to CaChs1p. RO-09-3143
      inhibited CaChs1p with a K(i) value of 0.55 nm in a manner that was non
      competitive to the substrate UDP-N-acetylglucosamine. RO-09-3143 also hampered
      the growth of the C. albicans cells with an MIC(50) value of 0.27 microm. In the
      presence of RO-09-3143, the C. albicans cells failed to form septa and displayed
      an aberrant morphology, confirming the involvement of the C. albicans Chs1p in
      septum formation. Although the effect of RO-09-3143 on the wild-type C. albicans
      was fungistatic, it caused cell death in the cachs2Delta null mutants but not in
      the cachs3Delta null mutants. Thus, it appears that in C. albicans, inhibition of
      CaChs1p causes cell growth arrest, but simultaneous inhibition of CaChs1p and
      CaChs2p is lethal.

PMID- 10930407
TI  - Functional analysis of the terminase large subunit, G2P, of Bacillus subtilis
      bacteriophage SPP1.
AB  - The terminase of bacteriophage SPP1, constituted by a large (G2P) and a small
      (G1P) subunit, is essential for the initiation of DNA packaging. A hexa-histidine
      G2P (H6-G2P), which is functional in vivo, possesses endonuclease, ATPase, and
      double-stranded DNA binding activities. H6-G2P introduces a cut with preference
      at the 5'-RCGG downward arrowCW-3' sequence. Distamycin A, which is a minor
      groove binder that mimics the architectural structure generated by G1P at pac,
      enhances the specific cut at both bona fide 5'-CTATTGCGG downward arrowC-3'
      sequences within pacC of SPP1 and SF6 phages. H6-G2P hydrolyzes rATP or dATP to
      the corresponding rADP or dADP and P(i). H6-G2P interacts with two discrete G1P
      domains (I and II). Full-length G1P and G1PDeltaN62 (lacking domain I) stimulate
      3.5- and 1.9-fold, respectively, the ATPase activity of H6-G2P. The results
      presented suggest that a DNA structure, artificially promoted by distamycin A or
      facilitated by the assembly of G1P at pacL and/or pacR, stimulates H6-G2P
      cleavage at both target sites within pacC. In the presence of two G1P decamers
      per H6-G2P monomer, the H6-G2P endonuclease is repressed, and the ATPase activity
      stimulated. Based on these results, we propose a model that can account for the
      role of terminase in headful packaging.

PMID- 10930409
TI  - Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch
      specific DNA N-glycosylase.
AB  - The human protein MED1 (also known as MBD4) was previously isolated in a two
      hybrid screening using the mismatch repair protein MLH1 as a bait, and shown to
      have homology to bacterial base excision repair DNA N-glycosylases/lyases. To
      define the mechanisms of action of MED1, we implemented a sensitive glycosylase
      assay amenable to kinetic analysis. We show that MED1 functions as a mismatch
      specific DNA N-glycosylase active on thymine, uracil, and 5-fluorouracil when
      these bases are opposite to guanine. MED1 lacks uracil glycosylase activity on
      single-strand DNA and abasic site lyase activity. The glycosylase activity of
      MED1 prefers substrates containing a G:T mismatch within methylated or
      unmethylated CpG sites; since G:T mismatches can originate via deamination of 5
      methylcytosine to thymine, MED1 may act as a caretaker of genomic fidelity at CpG
      sites. A kinetic analysis revealed that MED1 displays a fast first cleavage
      reaction followed by slower subsequent reactions, resulting in biphasic time
      course; this is due to the tight binding of MED1 to the abasic site reaction
      product rather than a consequence of enzyme inactivation. Comparison of kinetic
      profiles revealed that the MED1 5-methylcytosine binding domain and methylation
      of the mismatched CpG site are not required for efficient catalysis.

PMID- 10930408
TI  - Molecular mechanism of fibronectin gene activation by cyclic stretch in vascular
      smooth muscle cells.
AB  - Fibronectin plays an important role in vascular remodeling. A functional
      interaction between mechanical stimuli and locally produced vasoactive agents is
      suggested to be crucial for vascular remodeling. We examined the effect of
      mechanical stretch on fibronectin gene expression in vascular smooth muscle cells
      and the role of vascular angiotensin II in the regulation of the fibronectin gene
      in response to stretch. Cyclic stretch induced an increase in vascular
      fibronectin mRNA levels that was inhibited by actinomycin D and CV11974, an
      angiotensin II type 1 receptor antagonist; cycloheximide and PD123319, an
      angiotensin II type 2 receptor antagonist, did not affect the induction. In
      transfection experiments, fibronectin promoter activity was stimulated by stretch
      and inhibited by CV11974 but not by PD123319. DNA-protein binding experiments
      revealed that cyclic stretch enhanced nuclear binding to the AP-1 site, which was
      partially supershifted by antibody to c-Jun. Site-directed mutation of the AP-1
      site significantly decreased the cyclic stretch-mediated activation of
      fibronectin promoter. Furthermore, antisense c-jun oligonucleotides decreased the
      stretch-induced stimulation of the fibronectin promoter activity and the mRNA
      expression. These results suggest that cyclic stretch stimulates vascular
      fibronectin gene expression mainly via the activation of AP-1 through the
      angiotensin II type 1 receptor.

PMID- 10930410
TI  - The family of SMF metal ion transporters in yeast cells.
AB  - Metal ions are vital for all organisms, and metal ion transporters play a crucial
      role in maintaining their homeostasis. The yeast (Saccharomyces cerevisiae) Smf
      transporters and their homologs in other organisms have a central role in the
      accumulation of metal ions and their distribution in different tissues and
      cellular organelles. In this work we generated null mutations in each individual
      SMF gene in yeast as well as in all combinations of the genes. Each null mutation
      exhibited sensitivity to metal ion chelators at different concentrations. The
      combination of null mutants DeltaSMF1 + DeltaSMF2 and the triple null mutant
      Delta3SMF failed to grow on medium buffered at pH 8 and 7.5, respectively.
      Addition of 5 microm copper or 25 microm manganese alleviated the growth arrest
      at the high pH or in the presence of the chelating agent. The transport of
      manganese was analyzed in the triple null mutant and in this mutant expressing
      each Smf protein. Although overexpression of Smf1p and Smf2p resulted in uptake
      that was higher than wild type cells, the expression of Smf3p gave no significant
      uptake above that of the triple mutant Delta3SMF. Western analysis with antibody
      against Smf3p indicated that this transporter does not reach the plasma membrane
      and may function at the Golgi or post-Golgi complexes. The iron uptake resulting
      from expression of Smf1p and Smf2p was analyzed in a mutant in which its iron
      transporters FET3 and FET4 were inactivated. Overexpression of Smf1p gave rise to
      a significant iron uptake that was sensitive to the sodium concentrations in the
      medium. We conclude that the Smf proteins play a major role in copper and
      manganese homeostasis and, under certain circumstances, Smf1p may function in
      iron transport into the cells.

PMID- 10930411
TI  - Potentiation of Rho-A-mediated lysophosphatidic acid activity by
      hyperinsulinemia.
AB  - We have shown previously that insulin promotes phosphorylation and activation of
      farnesyltransferase and geranylgeranyltransferase (GGTase) II. We have now
      examined the effect of insulin on geranylgeranyltransferase I in MCF-7 breast
      cancer cells. Insulin increased GGTase I activity 3-fold and augmented the
      amounts of geranylgeranylated Rho-A by 18%. Both effects of the insulin were
      blocked by an inhibitor of GGTase I, GGTI-286. The insulin-induced increases in
      the amounts of geranylgeranylated Rho-A resulted in potentiation of the Rho-A
      mediated effects of lysophosphatidic acid (LPA) on a serum response element
      luciferase construct. Preincubation of cells with insulin augmented the LPA
      stimulated serum response element-luciferase activation to 12-fold, compared with
      just 6-fold for LPA alone (p < 0.05). The potentiating effect of insulin was dose
      dependent, inhibited by GGTI-286 and not mimicked by insulin-like growth factor
      1. We conclude that insulin activates GGTase I, increases the amounts of
      geranylgeranylated Rho-A protein, and potentiates the Rho-A-dependent nuclear
      effects of LPA in MCF-7 breast cancer cells.

PMID- 10930413
TI  - Maintenance of vascular integrity in the embryo requires signaling through the
      fibroblast growth factor receptor.
AB  - Basic fibroblast growth factor (FGF)-2 is important for vessel formation and/or
      maintenance of vascular integrity in the embryo. FGF signaling may be mediated
      through transmembrane tyrosine kinase receptors or directly through intracellular
      pathways that do not involve receptor activation. To determine the role of
      receptor-mediated signaling in endothelial cells, an adenovirus encoding
      truncated FGF receptor (FGFR)-1, under the control of the cytomegalovirus
      promoter, was expressed in endothelial cells. FGF signaling was impaired, as
      indicated by inhibition of MAPK phosphorylation. Functional consequences included
      inhibition of endothelial cell migration and induction of apoptosis. To address
      the role of endothelial FGFR signaling in vascular development, recombinant
      adenovirus encoding a dominant-negative FGFR was injected into the sinus venosus
      of embryonic day 9.0 cultured mouse embryos. Previous studies demonstrated that
      transgenes delivered via adenovirus, under the control of the cytomegalovirus
      promoter, are expressed selectively in the developing vasculature. Embryos
      expressing a control adenovirus developed normally, whereas those expressing the
      FGFR-1 mutant exhibited abnormal embryonic and extra-embryonic vascular
      development. These data demonstrate that FGF, by signaling through the FGFR,
      plays a pivotal role in the development and maintenance of a mature vascular
      network in the embryo.

PMID- 10930412
TI  - Androgen receptor interacts with a novel MYST protein, HBO1.
AB  - The androgen receptor (AR), a member of the nuclear receptor superfamily, plays a
      central role in male sexual differentiation and prostate cell proliferation.
      Results of treating prostate cancer by androgen ablation indicate that signals
      mediated through AR are critical for the growth of these tumors. Like other
      nuclear receptors, AR exerts its transcriptional function by binding to cis
      elements upstream of promoters and interacting with other transcriptional factors
      (e.g. activators, repressors and modulators). To determine the mechanism of AR
      regulated transcription, we used the yeast two-hybrid system to identify AR
      associated proteins. One of the proteins we identified is identical to the human
      origin recognition complex-interacting protein termed HBO1. A ligand-enhanced
      interaction between AR and HBO1 was further confirmed in vivo and in vitro.
      Immunofluorescence experiments showed that HBO1 is a nuclear protein, and
      Northern blot analysis revealed that it is ubiquitously expressed, with the
      highest levels present in human testis. HBO1 belongs to the MYST family, which is
      characterized by a highly conserved C2HC zinc finger and a putative histone
      acetyltransferase domain. Surprisingly, two yeast members of the MYST family,
      SAS2 and SAS3, have been shown to function as transcription silencers, despite
      the presence of the histone acetyltransferase domain. Using a GAL4 DNA-binding
      domain assay, we mapped a transcriptional repression domain within the N-terminal
      region of HBO1. Transient transfection experiments revealed that HBO1
      specifically repressed AR-mediated transcription in both CV-1 and PC-3 cells.
      These results indicate that HBO1 is a new AR-interacting protein capable of
      modulating AR activity. It could play a significant role in regulating AR
      dependent genes in normal and prostate cancer cells.

PMID- 10930414
TI  - Reduction of sphingomyelin level without accumulation of ceramide in Chinese
      hamster ovary cells affects detergent-resistant membrane domains and enhances
      cellular cholesterol efflux to methyl-beta -cyclodextrin.
AB  - We examined the effects of reduction of sphingomyelin level on cholesterol
      behavior in cells using 2 types of Chinese hamster ovary cell mutants deficient
      in sphingomyelin synthesis: LY-A strain defective in intracellular trafficking of
      ceramide for sphingomyelin synthesis, and LY-B strain defective in the enzyme
      catalyzing the initial step of sphingolipid biosynthesis. Although the
      sphingomyelin content in LY-A and LY-B cells was approximately 40 and
      approximately 15%, respectively, of the wild-type level without accumulation of
      ceramide, these mutant cells were almost identical in cholesterol content and
      also in plasma membrane cholesterol level to the wild-type cells. However,
      density gradient fractionation analysis of Triton X-100-treated lysates of cells
      prelabeled with [(3)H]cholesterol showed that the [(3)H]cholesterol level in the
      low-density floating fraction was lower in sphingomyelin-deficient cells than in
      wild-type cells. When cells were exposed to methyl-beta-cyclodextrin, cholesterol
      was more efficiently fluxed from sphingomyelin-deficient cells than wild-type
      cells. These results suggest that the steady state level of cholesterol at the
      plasma membrane is little affected by the sphingomyelin levels in Chinese hamster
      ovary cells, but that sphingomyelin levels play an important role in the
      retention of cholesterol in the plasma membrane against efflux to extracellular
      cholesterol-acceptors, due to interaction between sphingomyelin and cholesterol
      in detergent-resistant membrane domains.

PMID- 10930415
TI  - Regulation of the bovine kidney microsomal chloride channel p64 by p59fyn, a Src
      family tyrosine kinase.
AB  - p64 is a chloride channel of intracellular membranes which is present in
      regulated secretory vesicles. Mechanisms by which the p64 channel could be
      regulated are largely unknown. p59(fyn) is a non-receptor tyrosine kinase of the
      Src family that has been implicated in a variety of intracellular signaling
      events. The N-terminal portion of p64 has several potential binding sites for Src
      family SH2 domains. In this paper, we demonstrate that p64 becomes tyrosine
      phosphorylated when co-expressed with p59(fyn) in HeLa cells. We show that co
      expression of p64 with p59(fyn) renders p64 a ligand for the SH2 domain of
      p59(fyn) and this SH2 binding is eliminated by treating p64 with alkaline
      phosphatase. Using site-directed mutagenesis, we find that tyrosine 33 in the p64
      sequence is necessary for SH2 binding. We also characterized p64-p59(fyn)
      interactions using native material from bovine kidney. We found that a small
      fraction of native kidney p64 can bind Fyn SH2 in vitro. Immunoprecipitation of
      p64 from solubilized kidney membranes yields a kinase activity with the same
      mobility by SDS-polyacrylamide gel electrophoresis as authentic bovine p59(fyn).
      Finally, we demonstrate that co-expression of p64 and p59(fyn) in HeLa cells
      results in enhanced p64-associated chloride channel activity.

PMID- 10930416
TI  - Poly(A) tail-dependent exonuclease AtRrp41p from Arabidopsis thaliana rescues 5.8
      S rRNA processing and mRNA decay defects of the yeast ski6 mutant and is found in
      an exosome-sized complex in plant and yeast cells.
AB  - Eukaryotic 3'-->5' exonucleolytic activities are essential for a wide variety of
      reactions of RNA maturation and metabolism, including processing of rRNA, small
      nuclear RNA, and small nucleolar RNA, and mRNA decay. Two related but distinct
      forms of a complex containing 10 3'-->5' exonucleases, the exosome, are found in
      yeast nucleus and cytoplasm, respectively, and related complexes exist in human
      cells. Here we report on the characterization of the AtRrp41p, an Arabidopsis
      thaliana homolog of the Saccharomyces cerevisiae exosome subunit Rrp41p (Ski6p).
      Purified recombinant AtRrp41p displays a processive phosphorolytic exonuclease
      activity and requires a single-stranded poly(A) tail on a substrate RNA as a
      "loading pad." The expression of the Arabidopsis RRP41 cDNA in yeast rescues the
      5.8 S rRNA processing and 3'-->5' mRNA degradation defects of the yeast ski6-100
      mutant. However, neither of these defects can explain the conditional lethal
      phenotype of the ski6-100 strain. Importantly, AtRrp41p shares additional
      function(s) with the yeast Rrp41p which are essential for cell viability because
      it also rescues the rrp41 (ski6) null mutant. AtRrp41p is found predominantly in
      a high molecular mass complex in Arabidopsis and in yeast cells, and it interacts
      in vitro with the yeast Rrp44p and Rrp4p exosome subunits, suggesting that it can
      participate in evolutionarily conserved interactions that could be essential for
      the integrity of the exosome complex.

PMID- 10930417
TI  - Inhibition of six serine proteinases of the human coagulation system by mutants
      of bovine pancreatic trypsin inhibitor.
AB  - A series of 12 bovine pancreatic trypsin inhibitor variants mutated in the P(4)
      and P(3) positions of the canonical binding loop containing additional K15R and
      M52L mutations were used to probe the role of single amino acid substitutions on
      binding to bovine trypsin and to the following human proteinases involved in
      blood clotting: plasmin, plasma kallikrein, factors X(a) and XII(a), thrombin,
      and protein C. The mutants were expressed in Escherichia coli as fusion proteins
      with the LE1413 hydrophobic polypeptide and purified from inclusion bodies; these
      steps were followed by CNBr cleavage and oxidative refolding. The mutants
      inhibited the blood-clotting proteinases with association constants in the range
      of 10(3)-10(10) m(-)(1). Inhibition of plasma kallikrein, factors X(a) and
      XII(a), thrombin, and protein C could be improved by up to 2 orders of magnitude
      by the K15R substitution. The highest increase in the association constant for
      P(3) mutant was measured for factor XII(a); P13S substitution increased the K(a)
      value 58-fold. Several other substitutions at P(3) resulted in about 10-fold
      increase for factor X(a), thrombin, and protein C. The cumulative P(3) and P(1)
      effects on K(a) values for the strongest mutant compared with the wild type
      bovine pancreatic trypsin inhibitor were in the range of 2.2- (plasmin) to 4,000
      fold (factors XII(a) and X(a)). The substitutions at the P(4) site always caused
      negative effects (a decrease in the range from over 1,000- to 1.3-fold) on
      binding to all studied enzymes, including trypsin. Thermal stability studies
      showed a very large decrease of the denaturation temperature (about 22 degrees C)
      for all P(4) mutants, suggesting that substitution of the wild type Gly-12
      residue leads to a change in the binding loop conformation manifesting itself in
      non-optimal binding to the proteinase active site.

PMID- 10930418
TI  - Complete protection by alpha-crystallin of lens sorbitol dehydrogenase undergoing
      thermal stress.
AB  - Sorbitol dehydrogenase (l-iditol:NAD(+) 2-oxidoreductase, E.C. 1.1.1. 14) (SDH)
      was significantly protected from thermally induced inactivation and aggregation
      by bovine lens alpha-crystallin. An alpha-crystallin/SDH ratio as low as 1:2 in
      weight was sufficient to preserve the transparency of the enzyme solution kept
      for at least 2 h at 55 degrees C. Moreover, an alpha-crystallin/SDH ratio of 5:1
      (w/w) was sufficient to preserve the enzyme activity fully at 55 degrees C for at
      least 40 min. The protection by alpha-crystallin of SDH activity was essentially
      unaffected by high ionic strength (i.e. 0.5 m NaCl). On the other hand, the
      transparency of the protein solution was lost at a high salt concentration
      because of the precipitation of the alpha-crystallin/SDH adduct. Magnesium and
      calcium ions present at millimolar concentrations antagonized the protective
      action exerted by alpha-crystallin against the thermally induced inactivation and
      aggregation of SDH. The lack of protection of alpha-crystallin against the
      inactivation of SDH induced at 55 degrees C by thiol blocking agents or EDTA
      together with the additive effect of NADH in stabilizing the enzyme in the
      presence of alpha-crystallin suggest that functional groups involved in catalysis
      are freely accessible in SDH while interacting with alpha-crystallin. Two
      different adducts between alpha-crystallin and SDH were isolated by gel
      filtration chromatography. One adduct was characterized by a high M(r) of
      approximately 800,000 and carried exclusively inactive SDH. A second adduct,
      carrying active SDH, had a size consistent with an interaction of the enzyme with
      monomers or low M(r) aggregates of alpha-crystallin. Even though it had a reduced
      efficiency with respect to alpha-crystallin, bovine serum albumin was shown to
      mimic the chaperone-like activity of alpha-crystallin in protecting SDH from
      thermal denaturation. These findings suggest that the multimeric structural
      organization of alpha-crystallin may not be a necessary requirement for the
      stabilization of the enzyme activity.

PMID- 10930419
TI  - XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage.
AB  - The IAP (inhibitor of apoptosis) family of anti-apoptotic proteins regulates
      programmed cell death. Of the six known human IAP-related proteins, XIAP is the
      most potent inhibitor. To study the mechanistic effects of XIAP on DNA damage
      induced apoptosis, we prepared U-937 cells that stably overexpress XIAP. The
      results demonstrate that XIAP inhibits apoptosis induced by 1-[beta-d
      arabinofuranosyl]cytosine (ara-C) and other genotoxic agents. XIAP had no
      detectable effect on ara-C-induced release of mitochondrial cytochrome c and
      attenuated cleavage of procaspase-9. In addition, we show that ara-C induces the
      association of XIAP with the cleaved fragments of caspase-9 and thereby
      inhibition of caspase-9 activity. The results also demonstrate that ara-C induces
      cleavage of procaspase-3 by a caspase-8-dependent mechanism and that XIAP
      inhibits caspase-3 activity. These results demonstrate that XIAP functions
      downstream of procaspase-9 cleavage as an inhibitor of both proteolytically
      processed caspase-9 and -3 in the cellular response to genotoxic stress.

PMID- 10930420
TI  - Specific recognition of DNA by integration host factor. Glutamic acid 44 of the
      beta-subunit specifies the discrimination of a T:A from an A:T base pair without
      directly contacting the DNA.
AB  - Integration host factor (IHF) is a protein that binds to the H' site of
      bacteriophage lambda with sequence specificity. Genetic experiments implicated
      amino acid residue Glu(44) of the beta-subunit of IHF in discrimination against
      substitution of A for T at position 44 of the TTR submotif of the binding site
      (Lee, E. C., Hales, L. M., Gumport, R. I., Gardner, J. F. (1992) EMBO J., 11, 305
      313). We have extended this observation by generating all possible single-base
      substitutions at positions 43, 44, and 45 of the H' site. IHF failed to bind
      these H' site substitution mutants in vivo. The K(d)(app) value for each H' site
      substitution, except for H'45A mutant, was reduced >2000-fold relative to the
      wild-type site. Substitution of amino acid beta-Glu(44) with alanine prevented
      IHF from discriminating against the H'44A variant but not the other H' site
      substitution mutants. Further analysis with other substitutions at position
      beta44 demonstrated that both oxygens of the wild-type glutamic acid are
      necessary for discrimination of AT at position 44. Because the beta-Glu(44)
      residue does not contact the DNA, this residue probably enforces binding
      specificity indirectly through interaction with amino acids that themselves
      contact the DNA.

PMID- 10930422
TI  - Reprimo, a new candidate mediator of the p53-mediated cell cycle arrest at the G2
      phase.
AB  - A novel gene, Reprimo, in which induction in cells exposed to X-irradiation is
      dependent on p53 expression, has been isolated. Ectopic p53 expression results in
      the induction of its mRNA. Reprimo is a highly glycosylated protein and, when
      ectopically expressed, it is localized in the cytoplasm and induces G(2) arrest
      of the cell cycle. In the arrested cells, both Cdc2 activity and nuclear
      translocation of cyclin B1 are inhibited, suggesting the involvement of Reprimo
      in the Cdc2.cyclin B1 regulation pathway. Thus, Reprimo may be a new member
      involved in the regulation of p53-dependent G(2) arrest of the cell cycle.

PMID- 10930423
TI  - Cysteine-scanning mutagenesis of transmembrane segments 4 and 5 of the Tn10
      encoded metal-tetracycline/H+ antiporter reveals a permeability barrier in the
      middle of a transmembrane water-filled channel.
AB  - Cysteine-scanning mutants as to putative transmembrane segments 4 and 5 and the
      flanking regions of Tn10-encoded metal-tetracycline/H(+) antiporter (TetA(B))
      were constructed. All mutants were normally expressed. Among the 57 mutants (L99C
      to I155C), nine conserved arginine-, aspartate-, and glycine-replaced ones
      exhibited greatly reduced tetracycline resistance and almost no transport
      activity, and five conserved glycine- and proline-replaced mutants exhibited
      greatly reduced tetracycline transport activity in inverted membrane vesicles
      despite their high or moderate drug resistance. All other cysteine-scanning
      mutants retained normal drug resistance and normal tetracycline transport
      activity except for the L142C and I143C mutants. The transmembrane (TM) regions
      TM4 and TM5 were determined to comprise 20 amino acid residues, Leu-99 to Ile
      118, and 17 amino acid residues, Ala-136 to Ala-152, respectively, on the basis
      of N-[(14)C]ethylmaleimide ([(14)C]NEM) reactivity. The NEM reactivity patterns
      of the TM4 and TM5 mutants were quite different from each other. TM4 could be
      divided into two halves, that is, a NEM nonreactive periplasmic half and a
      periodically reactive cytoplasmic half, indicating that TM4 is tilted toward a
      water-filled transmembrane channel and that only its cytoplasmic half faces the
      channel. On the other hand, NEM-reactive mutations were observed periodically
      (every two residues) along the whole length of TM5. A permeability barrier for a
      membrane-impermeable sulfhydryl reagent, 4-acetamido-4'-maleimidylstilbene-2,2'
      disulfonic acid, was present in the middle of TM5 between Leu-142 and Gly-145,
      whereas all the NEM-reactive mutants as to TM4 were not accessible to 4-acetamido
      4'-maleimidylstilbene-2,2'-disulfonic acid, indicating that the channel-facing
      side of TM4 is located inside the permeability barrier. Tetracycline protected
      the G141C mutant from the NEM binding, whereas the other mutants in TM4 and TM5
      were not protected by tetracycline.

PMID- 10930424
TI  - The N-terminal sequence (residues 1-65) is essential for dimerization,
      activities, and peptide binding of Escherichia coli DsbC.
AB  - Limited proteolysis of DsbC with trypsin resulted in a compact and stable C
      terminal fragment (residues 66-216), fDsbC, which retains the active site
      sequence, -Cys(98)-Gly-Tyr-Cys(101)-, and shows only minor differences in
      conformation compared with that of the intact molecule. The pK(a) of active site
      thiol and the K(SS) with glutathione are very close to that of DsbC,
      respectively; however, fDsbC is inactive as an isomerase in catalyzing the
      formation of correct disulfide bonds in scrambled RNase A and denatured and
      reduced bovine pancreatic trypsin inhibitor and shows only 13% thiol-protein
      oxidoreductase activity (TPOR) of DsbC. In contrast to the dimeric DsbC, fDsbC
      exists as a monomer and has no chaperone activity in assisting the reactivation
      of denatured d-glyceraldehyde-3-phosphate dehydrogenase. The heterodimer of DsbC
      with the inactive DsbC carboxymethylated at both active site thiols shows about
      50% TPOR activity of DsbC but no isomerase activity, indicating that the DsbC
      subunit in the heterodimer displays full TPOR activity but little, if any,
      isomerase activity. It is concluded that the N-terminal sequence (residues 1-65)
      is essential for dimer formation and chaperone activity of DsbC. The active sites
      in both subunits of the dimeric DsbC appear to be essential for its isomerase
      activity.

PMID- 10930425
TI  - A direct interaction between proliferating cell nuclear antigen (PCNA) and Cdk2
      targets PCNA-interacting proteins for phosphorylation.
AB  - Proliferating cell nuclear antigen is best known as a DNA polymerase accessory
      protein but has more recently also been shown to have different functions in
      important cellular processes such as DNA replication, DNA repair, and cell cycle
      control. PCNA has been found in quaternary complexes with the cyclin kinase
      inhibitor p21 and several pairs of cyclin-dependent protein kinases and their
      regulatory partner, the cyclins. Here we show a direct interaction between PCNA
      and Cdk2. This interaction involves the regions of the PCNA trimer close to the C
      termini. We found that PCNA and Cdk2 form a complex together with cyclin A. This
      ternary PCNA-Cdk2-cyclin A complex was able to phosphorylate the PCNA binding
      region of the large subunit of replication factor C as well as DNA ligase I.
      Furthermore, PCNA appears to be a connector between Cdk2 and DNA ligase I and to
      stimulate phosphorylation of DNA ligase I. Based on our results, we propose the
      model that PCNA brings Cdk2 to proteins involved in DNA replication and possibly
      might act as an "adaptor" for Cdk2-cyclin A to PCNA-binding DNA replication
      proteins.

PMID- 10930426
TI  - Substrate specificity in glycoside hydrolase family 10. Structural and kinetic
      analysis of the Streptomyces lividans xylanase 10A.
AB  - Endoxylanases are a group of enzymes that hydrolyze the beta-1, 4-linked xylose
      backbone of xylans. They are predominantly found in two discrete sequence
      families known as glycoside hydrolase families 10 and 11. The Streptomyces
      lividans xylanase Xyl10A is a family 10 enzyme, the native structure of which has
      previously been determined by x-ray crystallography at a 2.6 A resolution
      (Derewenda, U., Swenson, L., Green, R., Wei, Y., Morosoli, R., Shareck, F.,
      Kluepfel, D., and Derewenda, Z. S. (1994) J. Biol. Chem. 269, 20811-20814). Here,
      we report the native structure of Xyl10A refined at a resolution of 1.2 A, which
      reveals many features such as the rare occurrence of a discretely disordered
      disulfide bond between residues Cys-168 and Cys-201. In order to investigate
      substrate binding and specificity in glycoside hydrolase family 10, the covalent
      xylobiosyl enzyme and the covalent cellobiosyl enzyme intermediates of Xyl10A
      were trapped through the use of appropriate 2-fluoroglycosides. The alpha-linked
      intermediate with the nucleophile, Glu-236, is in a (4)C(1) chair conformation as
      previously observed in the family 10 enzyme Cex from Cellulomonas fimi
      (Notenboom, V., Birsan, C., Warren, R. A. J., Withers, S. G., and Rose, D. R.
      (1998) Biochemistry 37, 4751-4758). The different interactions of Xyl10A with the
      xylobiosyl and cellobiosyl moieties, notably conformational changes in the -2 and
      -1 subsites, together with the observed kinetics on a range of aryl glycosides,
      shed new light on substrate specificity in glycoside hydrolase family 10.

PMID- 10930427
TI  - Truncated form of importin alpha identified in breast cancer cell inhibits
      nuclear import of p53.
AB  - Disruption of the function of tumor suppressor proteins occasionally can be
      dependent on their subcellular localization. In about 40% of the breast cancer
      tissues, p53 is found in the cytoplasm as opposed to the nucleus, where it
      resides in normal breast cells. This means that the regulation of subcellular
      location of p53 is an important mechanism in controlling its function. The
      transport factors required for the nuclear export of p53 and the mechanisms of
      their nuclear export have been extensively characterized. However, little is
      known about the mechanism of nuclear import of p53. p53 contains putative nuclear
      localization signals (NLSs) which would interact with a nuclear transport factor,
      importin alpha. In this report we demonstrate that importin alpha binds to NLSI
      in p53 and mediates the nuclear import of p53. Reverse transcriptase-polymerase
      chain reaction and sequencing analyses showed that a truncated importin alpha
      deleted the region encoding the putative NLS-binding domain of p53, suggesting
      that it could not bind to NLSs of p53 proteins. Binding of importin alpha to p53
      was confirmed by using yeast two-hybrid assay. When expressed in CHO-K1 cells,
      the truncated importin alpha predominantly localized to the cytoplasm. In
      truncated importin alpha expressing cells, p53 preferentially localized to
      cytoplasmic sites as well. A significant increase in the p21(waf1/cip1) mRNA
      level and induction of apoptosis were also observed in importin alpha
      overexpressing cells. These results strongly suggest that importin alpha
      functions as a component of the NLS receptor for p53 and mediates nuclear import
      of p53.

PMID- 10930428
TI  - Human p53 is phosphorylated on serines 6 and 9 in response to DNA damage-inducing
      agents.
AB  - To characterize the sites in human p53 that become phosphorylated in response to
      DNA damage, we have developed polyclonal antibodies that recognize p53 only when
      it is phosphorylated at specific sites. Several attempts to generate an antibody
      to p53 phosphorylated at Ser(6) using a phosphoserine-containing peptide as an
      immunogen were unsuccessful; however, phosphorylation-specific antibodies were
      produced by using the phosphoserine mimetic, l-2-amino-4-phosphono-4, 4
      difluorobutanoic acid (F(2)Pab), in place of phosphoserine. Fmoc-F(2)Pab was
      prepared by an improved synthesis and chemically incorporated using solid phase
      peptide synthesis. Affinity-purified antibodies elicited by immunizing rabbits
      with an F(2)Pab peptide coupled to keyhole limpet hemocyanin recognized a p53(1
      39) peptide phosphorylated only at Ser(6) but not the unphosphorylated peptide or
      the same peptide phosphorylated at Ser(9), Ser(15), Ser(20), Ser(33), or Ser(37).
      Untreated A549 cells exhibited a background of constitutive phosphorylation at
      Ser(6) that increased approximately 10-fold upon exposure to either ionizing
      radiation or UV light. Similar results were obtained for Ser(9) using antibodies
      raised against a conventional phosphopeptide. Ser(9) was phosphorylated by casein
      kinase 1 in vitro in a phosphoserine 6-dependent manner. Our data identify two
      additional DNA damage-induced phosphorylations in human p53 and show that F(2)Pab
      derivatized peptides can be used to develop phosphorylation site-specific
      polyclonal antibodies.

PMID- 10930429
TI  - ATP for the DNA ligation step in base excision repair is generated from poly(ADP
      ribose).
AB  - In mammalian cells, the base excision repair (BER) pathway is the main route to
      counteract the mutagenic effects of DNA lesions. DNA nicks induce, among others,
      DNA polymerase activities and the synthesis of poly(ADP-ribose). It is shown here
      that poly(ADP-ribose) serves as an energy source for the final and rate-limiting
      step of BER, DNA ligation. This conclusion was drawn from experiments in which
      the fate of [(32)P]poly(ADP-ribose) or [(32)P]NAD added to HeLa nuclear extracts
      was systematically followed. ATP was synthesized from poly(ADP-ribose) in a
      pathway that strictly depended on nick-induced DNA synthesis. NAD was used for
      the synthesis of poly(ADP-ribose), which, in turn, was converted to ATP by
      pyrophosphorylytic cleavage utilizing the pyrophosphate generated from dNTPs
      during DNA synthesis. The adenylyl moiety was then preferentially used to
      adenylate DNA ligase III, from which it was transferred to the 5'-phosphoryl end
      of the nicked DNA. Finally, ligation to the 3'-OH end resulted in the release of
      AMP. When using NAD, but not poly(ADP-ribose), in the presence of 3
      aminobenzamide, the entire process was blocked, confirming poly(ADP-ribosyl)ation
      to be the essential initial step. Thus, poly(ADP-ribose) polymerase-1, DNA
      polymerase beta, and ligase III interact with x-ray repair cross-complementing
      protein-1 within the BER complex, which ensures that ATP is generated and
      specifically used for DNA ligation.

PMID- 10930431
TI  - Multiple topological domains mediate subtype-specific internalization of the M2
      muscarinic acetylcholine receptor.
AB  - Endocytosis of agonist-activated G protein-coupled receptors (GPCRs) is required
      for both resensitization and recycling to the cell surface as well as lysosomal
      degradation. Thus, this process is crucial for regulation of receptor signaling
      and cellular responsiveness. Although many GPCRs internalize into clathrin-coated
      vesicles in a dynamin-dependent manner, some receptors, including the M(2)
      muscarinic acetylcholine receptor (mAChR), can also exhibit dynamin-independent
      internalization. We have identified five amino acids, located in the sixth and
      seventh transmembrane domains and the third intracellular loop, that are
      essential for agonist-induced M(2) mAChR internalization via a dynamin
      independent mechanism in JEG-3 choriocarcinoma cells. Substitution of these
      residues into the M(1) mAChR, which does not internalize in these cells, is
      sufficient for conversion to the internalization-competent M(2) mAChR phenotype,
      whereas removal of these residues from the M(2) mAChR blocks internalization.
      Cotransfection of a dominant-negative isoform of dynamin has no effect on M(2)
      mAChR internalization. An internalization-incompetent M(2) mutant that lacks a
      subset of the necessary residues can still internalize via a G protein-coupled
      receptor kinase-2 and beta-arrestin-dependent pathway. Furthermore,
      internalization is independent of the signal transduction pathway that is
      activated. These results identify a novel motif that specifies structural
      requirements for subtype-specific dynamin-independent internalization of a GPCR.

PMID- 10930430
TI  - MAPK mediation of hypertonicity-stimulated cyclooxygenase-2 expression in renal
      medullary collecting duct cells.
AB  - We have previously shown that hypertonicity stimulates cyclooxygenase-2 (COX-2)
      expression in cultured medullary epithelial cells. The aims of the present study
      were (i) to examine the role of cytoplasmic signaling through MAPK pathways in
      tonicity regulation of COX-2 expression in collecting duct cells and (ii) to
      assess the possible contribution of COX-2 to the survival of inner medullary
      collecting duct (IMCD) cells under hypertonic conditions. In mIMCD-K2 cells, a
      cell line derived from mouse IMCDs, hypertonicity induced a marked increase in
      COX-2 protein expression. The stimulation was reduced significantly by inhibition
      of MEK1 (PD-98059, 5-50 microm) and p38 (SB-203580, 5-100 microm) and was almost
      abolished by the combination of the two compounds. To study the role of JNK in
      tonicity-stimulated COX-2 expression, IMCD-3 cell lines stably transfected with
      dominant-negative mutants of three JNKs (JNK-1, -2, and -3) were used.
      Hypertonicity-stimulated COX-2 protein expression was significantly reduced in
      dominant-negative JNK-2-expressing cells and was unchanged in dominant-negative
      JNK-1- and JNK-3-expressing cells compared with controls. The reduction of COX-2
      expression was associated with greatly reduced viability of dominant-negative JNK
      2-expressing cells during hypertonicity treatment. 4-amino-5-(4-chlorophenyl)-7
      (t-butyl)pyrazolo[3,4-d]pyrimidine (PP2) (2-8 microm), an inhibitor of Src
      kinases, reduced the tonicity-stimulated COX-2 expression in a dose-dependent
      manner, whereas PP3, an inactive analog of PP2, had no effect. Inhibition of COX
      2 activity by NS-398 (30-90 microm) and SC-58236 (10-20 microm) significantly
      reduced viability of mIMCD-K2 cells subjected to prolonged hypertonic treatment.
      We conclude that 1) all three members of the MAPK family (ERK, JNK-2, and p38) as
      well as Src kinases are required for tonicity-stimulated COX-2 expression in
      mouse collecting duct cells and that 2) COX-2 may play a role in cell survival of
      medullary cells under hypertonic conditions.

PMID- 10930433
TI  - Strategies and prospects for finding insulin resistance genes.

PMID- 10930434
TI  - Interactions between insulin resistance and insulin secretion in the development
      of glucose intolerance.

PMID- 10930435
TI  - Hyaluronan is not just a goo!

PMID- 10930436
TI  - Sickle cell anemia as an inflammatory disease.

PMID- 10930437
TI  - Local pH elevation mediated by the intrabacterial urease of Helicobacter pylori
      cocultured with gastric cells.
AB  - Helicobacter pylori resists gastric acidity by modulating the proton-gated urea
      channel UreI, allowing for pH(out)-dependent regulation of urea access to
      intrabacterial urease. We employed pH- and Ca(2+)-sensitive fluorescent dyes and
      confocal microscopy to determine the location, rate, and magnitude of pH changes
      in an H. pylori-AGS cell coculture model, comparing wild-type bacteria with
      nonpolar ureI-deletion strains (ureI-ve). Addition of urea at pH 5.5 to the
      coculture resulted first in elevation of bacterial periplasmic pH, followed by an
      increase of medium pH and then pH in AGS cells. No change in periplasmic pH
      occurred in ureI-deletion mutants, which also induced a slower increase in the pH
      of the medium. Pretreatment of the mutant bacteria with the detergent C(12)E(8)
      before adding urea resulted in rapid elevation of bacterial cytoplasmic pH and
      medium pH. UreI-dependent NH(3) generation by intrabacterial urease buffers the
      bacterial periplasm, enabling acid resistance at the low urea concentrations
      found in gastric juice. Perfusion of AGS cells with urea-containing medium from
      coculture at pH 5.5 did not elevate pH(in) or [Ca(2+)](in), unless the
      conditioned medium was first neutralized to elevate the NH(3)/NH(4)(+) ratio.
      Therefore, cellular effects of intrabacterial ammonia generation under acidic
      conditions are indirect and not through a type IV secretory complex. The pH(in)
      and [Ca(2+)](in) elevation that causes the NH(3)/NH(4)(+) ratio to increase after
      neutralization of infected gastric juice may contribute to the gastritis seen
      with H. pylori infection.

PMID- 10930439
TI  - C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene
      products and treat ongoing adjuvant arthritis.
AB  - Depending on the method of immunization, a single administration of CFA may
      result in the development of a local inflammatory process or chronic polyadjuvant
      induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1 alpha,
      MCP-1, MIP-1 beta, and RANTES to Lewis rats and confirmed that each of these
      vaccines induced immunological memory to the corresponding gene product. Upon
      induction of disease, this memory effectively inhibited the development of the
      autoimmune condition. Self-specific Ab's developed in DNA-vaccinated animals were
      neutralizing in vitro and could adoptively transfer the beneficial effect of each
      vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1 alpha,
      or RANTES inhibited the development and progression of AA, even when each vaccine
      was administered only after the onset of disease. This suggests a highly
      effective way by which the immune system could be re-educated to generate
      protective immunity against its own harmful activities.

PMID- 10930438
TI  - Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and
      hyaluronan-mediated transformation of epithelium to mesenchyme.
AB  - We identified hyaluronan synthase-2 (Has2) as a likely source of hyaluronan (HA)
      during embryonic development, and we used gene targeting to study its function in
      vivo. Has2(-/-) embryos lack HA, exhibit severe cardiac and vascular
      abnormalities, and die during midgestation (E9.5-10). Heart explants from Has2(-/
      ) embryos lack the characteristic transformation of cardiac endothelial cells
      into mesenchyme, an essential developmental event that depends on receptor
      mediated intracellular signaling. This defect is reproduced by expression of a
      dominant-negative Ras in wild-type heart explants, and is reversed in Has2(-/-)
      explants by gene rescue, by administering exogenous HA, or by expressing
      activated Ras. Conversely, transformation in Has2(-/-) explants mediated by
      exogenous HA is inhibited by dominant-negative Ras. Collectively, our results
      demonstrate the importance of HA in mammalian embryogenesis and the pivotal role
      of Has2 during mammalian development. They also reveal a previously unrecognized
      pathway for cell migration and invasion that is HA-dependent and involves Ras
      activation.

PMID- 10930441
TI  - Persistence of platelet thrombus formation in arterioles of mice lacking both von
      Willebrand factor and fibrinogen.
AB  - We used intravital microscopy to observe the formation of platelet plugs in
      ferric chloride-injured arterioles of live mice. With this model, we evaluated
      thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg),
      the two key ligands known to mediate platelet adhesion and aggregation. In vWF(-/
      ) mice, despite the presence of arterial shear, delayed platelet adhesion
      occurred and stable thrombi formed. In many mice, a persisting high-shear channel
      never occluded. Abundant thrombi formed in Fg(-/-) mice, but they detached from
      the subendothelium, which ultimately caused downstream occlusion in all cases.
      Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with
      properties characteristic of both mutations, leading to vessel occlusion in the
      majority of vessels. Platelets of these doubly deficient mice specifically
      accumulated fibronectin in their alpha-granules, suggesting that fibronectin
      could be the ligand supporting the platelet aggregation.

PMID- 10930440
TI  - Insulin restores neuronal nitric oxide synthase expression and function that is
      lost in diabetic gastropathy.
AB  - Gastrointestinal dysfunction is common in diabetic patients. In genetic (nonobese
      diabetic) and toxin-elicited (streptozotocin) models of diabetes in mice, we
      demonstrate defects in gastric emptying and nonadrenergic, noncholinergic
      relaxation of pyloric muscle, which resemble defects in mice harboring a deletion
      of the neuronal nitric oxide synthase gene (nNOS). The diabetic mice manifest
      pronounced reduction in pyloric nNOS protein and mRNA. The decline of nNOS in
      diabetic mice does not result from loss of myenteric neurons. nNOS expression and
      pyloric function are restored to normal levels by insulin treatment. Thus
      diabetic gastropathy in mice reflects an insulin-sensitive reversible loss of
      nNOS. In diabetic animals, delayed gastric emptying can be reversed with a
      phosphodiesterase inhibitor, sildenafil. These findings have implications for
      novel therapeutic approaches and may clarify the etiology of diabetic
      gastropathy.

PMID- 10930442
TI  - A potential role of activated NF-kappa B in the pathogenesis of euthyroid sick
      syndrome.
AB  - Euthyroid sick syndrome, characterized by low serum 3,5, 3'-triiodothyronine
      (T(3)) with normal L-thyroxine levels, is associated with a wide variety of
      disorders including sepsis, malignancy, and AIDS. The degree of low T(3) in
      circulation has been shown to correlate with the severity of the underlying
      disorders and with the prognosis. Elevated TNF-alpha levels, which accompany
      severe illness, are associated with decreased activity of type I 5'-deiodinase
      (5'-DI) in liver, leading us to speculate that high levels of this factor
      contribute to euthyroid sick syndrome. Here we demonstrate that the activation of
      NF-kappa B by TNF-alpha interferes with thyroid-hormone action as demonstrated by
      impairment of T(3)-dependent induction of 5'-DI gene expression in HepG2 cells.
      Inhibition of NF-kappa B action by a dominant-negative NF-kappa B reversed this
      effect and allowed T(3) induction of 5'-DI. Furthermore, we show that an
      inhibitor of NF-kappa B activation, clarithromycin (CAM), can inhibit TNF-alpha
      induced activation of NF-kappa B and restore T(3)-dependent induction of 5'-DI
      mRNA and enzyme activity. These results suggest that NF-kappa B activation by TNF
      alpha is involved in the pathogenesis of euthyroid sick syndrome and that CAM
      could help prevent a decrease in serum T(3) levels and thus ameliorate euthyroid
      sick syndrome.

PMID- 10930443
TI  - In vivo alterations of IFN regulatory factor-1 and PIAS1 protein levels in cystic
      fibrosis epithelium.
AB  - Inducible nitric oxide synthase-2 (NOS2) expression has been shown to be reduced
      in cystic fibrosis (CF) epithelial cells. Reduced NOS2 expression is unexpected,
      given the inflammatory nature of CF airway disease, and is an indication that
      cell-signaling mechanisms necessary for proper NOS2 regulation are probably
      altered in CF epithelium. Therefore, we examined the expression levels of
      regulatory factors necessary for NOS2 expression in CF epithelium and showed that
      IFN regulatory factor-1 (IRF-1) is necessary for full NOS2 expression. Mice
      lacking IRF-1 expression have diminished epithelial NOS2 expression, as well as
      reduced NO-dependent chloride transport across the nasal epithelia. Furthermore,
      IRF-1 protein expression is reduced in nasal and intestinal epithelial cells from
      CF mice, suggesting a possible mechanism for the CF-related reduction of
      epithelial NOS2 expression. Active signal transducer and activator of
      transcription-1 (Stat1) is necessary for both NOS2 and IRF-1 expression. We found
      that protein levels of Stat1 were increased in CF cells, but that the active
      phosphorylated form of Stat1 was bound to the protein inhibitor of activated
      Stat1 (PIAS1). We propose that increased levels of PIAS1 diminish certain cell
      signaling pathways, resulting in reduced IRF-1 and NOS2 expression in CF
      epithelial cells.

PMID- 10930444
TI  - Hypoxia/reoxygenation causes inflammatory response in transgenic sickle mice but
      not in normal mice.
AB  - In sickle cell anemia, the initiation, progression, and resolution of a
      vasoocclusive episode may present features of ischemia-reperfusion injury, with
      recurrent episodes of ischemia/hypoxia and reoxygenation promoting inflammation.
      Here, we have tested the hypothesis that hypoxia/reoxygenation triggers
      inflammation in the transgenic sickle mouse. In these mice, even at ambient air,
      peripheral leukocyte counts are elevated by 1.7-fold and neutrophil counts by
      almost 3-fold. Two hours of hypoxia, followed by reoxygenation, induced a greater
      than normal rolling flux and adhesion of leukocytes in these mice, but no
      leukocyte extravasation. When 3 hours of hypoxia was followed by reoxygenation,
      sickle mice, but not normal mice, showed a distinct inflammatory response
      characterized by an increased number of adherent and emigrated leukocytes.
      Because these events, which are exaggerated in sickle mice, are not seen in
      response to hypoxia alone, we conclude that they represent a form of reperfusion
      injury. Studies using an H(2)O(2)-sensitive probe revealed clear evidence of
      oxidant production in vascular endothelial cells after hypoxia/reoxygenation in
      sickle mice. Infusion of an anti-P-selectin antibody, but not an anti-E-selectin
      antibody, completely inhibited this inflammatory response and significantly
      increased wall shear rates. These findings suggest that leukocyte-endothelium
      interaction contribute to vasoocclusive events in the sickle mice and perhaps in
      human sickle disease.

PMID- 10930445
TI  - Rapid oscillations in omental lipolysis are independent of changing insulin
      levels in vivo.
AB  - Abnormal fat metabolism plays an important role in the pathogenesis of obesity
      related type 2 diabetes mellitus. This study examined whether free fatty acid
      levels (FFAs), like insulin levels, oscillate rapidly in plasma. Peripheral and
      portal blood samples from dogs were assayed for FFA, glycerol, glucose, and
      insulin. FFA and glycerol showed correlated oscillatory profiles, with about 8
      pulses/hour. Omental lipolysis was also pulsatile, with about 10 pulses/hour, and
      insulin levels oscillated rapidly in plasma with about 7 pulses/hour. We applied
      an insulin clamp, beta-adrenergic blockade, or both together, to determine the
      driving force behind the FFA oscillation, and we analyzed our findings by
      approximate entropy (ApEn) for which lower values suggest regular pulses and
      higher values suggest disorder. Under basal conditions, ApEn was 0.3 +/- 0.2.
      With insulin not oscillating, FFA still cycled at about 9 pulses/hour and the
      ApEn was 0.2 +/- 0.1. In contrast, beta-blockade, either in the presence or
      absence of an insulin clamp, removed the FFA oscillation in three of nine dogs.
      In the other six dogs, the oscillatory profile was unchanged, but ApEn was
      significantly higher than basal values, suggesting that the regularity of the
      profile was disrupted. These results suggest that the FFA oscillation is driven
      by the central nervous system, not by insulin.

PMID- 10930446
TI  - A double mutation in families with periodic paralysis defines new aspects of
      sodium channel slow inactivation.
AB  - Hyperkalemic periodic paralysis (HyperKPP) is an autosomal dominant skeletal
      muscle disorder caused by single mutations in the SCN4A gene, encoding the human
      skeletal muscle voltage-gated Na(+) channel. We have now identified one allele
      with two novel mutations occurring simultaneously in the SCN4A gene. These
      mutations are found in two distinct families that had symptoms of periodic
      paralysis and malignant hyperthermia susceptibility. The two nucleotide
      transitions predict phenylalanine 1490-->leucine and methionine 1493-->isoleucine
      changes located in the transmembrane segment S5 in the fourth repeat of the alpha
      subunit Na(+) channel. Surprisingly, this mutation did not affect fast
      inactivation parameters. The only defect produced by the double mutant (F1490L
      M1493I, expressed in human embryonic kidney 293 cells) is an enhancement of slow
      inactivation, a unique behavior not seen in the 24 other disease-causing
      mutations. The behavior observed in these mutant channels demonstrates that
      manifestation of HyperKPP does not necessarily require disruption of slow
      inactivation. Our findings may also shed light on the molecular determinants and
      mechanism of Na(+) channel slow inactivation and help clarify the relationship
      between Na(+) channel defects and the long-term paralytic attacks experienced by
      patients with HyperKPP.

PMID- 10930448
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- 10930447
TI  - Inhibition of ubiquitin-proteasome pathway-mediated I kappa B alpha degradation
      by a naturally occurring antibacterial peptide.
AB  - Induction of NF-kappaB-dependent gene expression plays an important role in a
      number of biological processes including inflammation and ischemia-reperfusion
      injury. However, few attempts aimed at selective regulation of this transcription
      factor have been successful. We report here that a naturally occurring
      antibacterial peptide PR39 reversibly binds to the alpha 7 subunit of the 26S
      proteasome and blocks degradation of NF-kappa B inhibitor I kappa B alpha by the
      ubiquitin-proteasome pathway without affecting overall proteasome activity. I
      kappa B alpha phosphorylation and ubiquitination occur normally after PR39
      treatment, and binding of valosin-containing proteins is not impaired. The
      inhibition of I kappa B alpha degradation abolishes induction of NF-kappa B
      dependent gene expression in cell culture and in mouse models of acute
      pancreatitis and myocardial infarction, including upregulation of endothelial
      adhesion proteins VCAM-1 and ICAM-1. In the latter model, sustained infusion of
      PR39 peptide resulted in significant reduction of myocardial infarct size. PR39
      and related peptides may provide novel means to regulate cellular function and to
      control of NF-kappa B-dependent gene expression for therapeutic purposes.

PMID- 10930450
TI  - Critical activities of Rac1 and Cdc42Hs in skeletal myogenesis: antagonistic
      effects of JNK and p38 pathways.
AB  - The Rho family of GTP-binding proteins plays a critical role in a variety of
      cellular processes, including cytoskeletal reorganization and activation of
      kinases such as p38 and C-jun N-terminal kinase (JNK) MAPKs. We report here that
      dominant negative forms of Rac1 and Cdc42Hs inhibit the expression of the muscle
      specific genes myogenin, troponin T, and myosin heavy chain in L6 and C2
      myoblasts. Such inhibition correlates with decreased p38 activity. Active RhoA,
      RhoG, Rac1, and Cdc42Hs also prevent myoblast-to-myotube transition but affect
      distinct stages: RhoG, Rac1, and Cdc42Hs inhibit the expression of all muscle
      specific genes analyzed, whereas active RhoA potentiates their expression but
      prevents the myoblast fusion process. We further show by two different approaches
      that the inhibitory effects of active Rac1 and Cdc42Hs are independent of their
      morphogenic activities. Rather, myogenesis inhibition is mediated by the JNK
      pathway, which also leads to a cytoplasmic redistribution of Myf5. We propose
      that although Rho proteins are required for the commitment of myogenesis, they
      differentially influence this process, positively for RhoA and Rac1/Cdc42Hs
      through the activation of the SRF and p38 pathways, respectively, and negatively
      for Rac1/Cdc42Hs through the activation of the JNK pathway.

PMID- 10930451
TI  - Role of p97 and syntaxin 5 in the assembly of transitional endoplasmic reticulum.
AB  - Transitional endoplasmic reticulum (tER) consists of confluent rough and smooth
      endoplasmic reticulum (ER) domains. In a cell-free incubation system, low-density
      microsomes (1.17 g cc(-1)) isolated from rat liver homogenates reconstitute tER
      by Mg(2+)GTP- and Mg(2+)ATP-hydrolysis-dependent membrane fusion. The ATPases
      associated with different cellular activities protein p97 has been identified as
      the relevant ATPase. The ATP depletion by hexokinase or treatment with either N
      ethylmaleimide or anti-p97 prevented assembly of the smooth ER domain of tER.
      High-salt washing of low-density microsomes inhibited assembly of the smooth ER
      domain of tER, whereas the readdition of purified p97 with associated p47
      promoted reconstitution. The t-SNARE syntaxin 5 was observed within the smooth ER
      domain of tER, and antisyntaxin 5 abrogated formation of this same membrane
      compartment. Thus, p97 and syntaxin 5 regulate assembly of the smooth ER domain
      of tER and hence one of the earliest membrane differentiated components of the
      secretory pathway.

PMID- 10930452
TI  - The tumor suppressor p53 can both stimulate and inhibit ultraviolet light-induced
      apoptosis.
AB  - We have previously shown that the tumor suppressor p53 can play a protective role
      against UV-induced apoptosis in human fibroblasts. In the present study, we
      investigated whether the protective function of p53 expression is established
      before or after UV irradiation. Using a stable human cell line expressing a
      murine temperature-sensitive p53 in which p53 function could be tightly and
      reversibly regulated, we found that functional p53 stimulated the induction of
      apoptosis when expressed for as little as 4-12 h after UV irradiation and that
      this induction was not dependent on de novo protein synthesis. In contrast,
      expression of p53 for 12 h or more before UV irradiation reduced the extent of
      apoptosis even when functional p53 expression was maintained after irradiation.
      The protection conferred by p53 required ongoing protein synthesis and correlated
      with enhanced recovery of mRNA synthesis. Together, these results suggest that
      p53 induces distinct proapoptotic and antiapoptotic signals and that these
      opposing activities can be separated both temporally and by their requirement for
      de novo protein synthesis. These findings may have important implications for the
      refinement of gene therapy approaches combining p53 with pharmacological agents
      that target transcription or translation.

PMID- 10930453
TI  - Analysis of cortical flow models in vivo.
AB  - Cortical flow, the directed movement of cortical F-actin and cortical organelles,
      is a basic cellular motility process. Microtubules are thought to somehow direct
      cortical flow, but whether they do so by stimulating or inhibiting contraction of
      the cortical actin cytoskeleton is the subject of debate. Treatment of Xenopus
      oocytes with phorbol 12-myristate 13-acetate (PMA) triggers cortical flow toward
      the animal pole of the oocyte; this flow is suppressed by microtubules. To
      determine how this suppression occurs and whether it can control the direction of
      cortical flow, oocytes were subjected to localized manipulation of either the
      contractile stimulus (PMA) or microtubules. Localized PMA application resulted in
      redirection of cortical flow toward the site of application, as judged by
      movement of cortical pigment granules, cortical F-actin, and cortical myosin-2A.
      Such redirected flow was accelerated by microtubule depolymerization, showing
      that the suppression of cortical flow by microtubules is independent of the
      direction of flow. Direct observation of cortical F-actin by time-lapse confocal
      analysis in combination with photobleaching showed that cortical flow is driven
      by contraction of the cortical F-actin network and that microtubules suppress
      this contraction. The oocyte germinal vesicle serves as a microtubule organizing
      center in Xenopus oocytes; experimental displacement of the germinal vesicle
      toward the animal pole resulted in localized flow away from the animal pole. The
      results show that 1) cortical flow is directed toward areas of localized
      contraction of the cortical F-actin cytoskeleton; 2) microtubules suppress
      cortical flow by inhibiting contraction of the cortical F-actin cytoskeleton; and
      3) localized, microtubule-dependent suppression of actomyosin-based contraction
      can control the direction of cortical flow. We discuss these findings in light of
      current models of cortical flow.

PMID- 10930454
TI  - Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth
      factor/scatter factor-induced cell scattering.
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) induces cell scattering through
      the tyrosine kinase-type HGF/SF receptor c-Met. We have previously shown that Rho
      small G protein (Rho) is involved in the HGF/SF-induced scattering of Madin-Darby
      canine kidney (MDCK) cells by regulating at least the assembly and disassembly of
      stress fibers and focal adhesions, but it remains unknown how c-Met regulates Rho
      activity. We have found here a novel signaling pathway of c-Met consisting of SHP
      2-Rho that regulates the assembly and disassembly of stress fibers and focal
      adhesions in MDCK cells. SHP-2 is a protein-tyrosine phosphatase that contains
      src homology-2 domains. Expression of a dominant negative mutant of SHP-2 (SHP-2
      C/S) markedly increased the formation of stress fibers and focal adhesions in
      MDCK cells and inhibited their scattering. C3, a Clostridium botulinum ADP
      ribosyltransferase, and Y-27632, a specific inhibitor for ROCK, reversed the
      stimulatory effect of SHP-2-C/S on stress fiber formation and the inhibitory
      effect on cell scattering. Vav2 is a GDP/GTP exchange protein for Rho. Expression
      of a dominant negative mutant of Vav2 blocked the stimulatory effect of SHP-2-C/S
      on stress fiber formation. Conversely, expression of mutants of Vav2 that
      increased stress fiber formation inhibited HGF/SF-induced cell scattering. These
      results indicate that SHP-2 physiologically modulates the activity of Rho to form
      stress fibers and focal adhesions and thereby regulates HGF/SF-induced cell
      scattering. In addition, Vav2 may be involved in the SHP-2-Rho pathway.

PMID- 10930455
TI  - Potential role for protein kinases in regulation of bidirectional endoplasmic
      reticulum-to-Golgi transport revealed by protein kinase inhibitor H89.
AB  - Recent evidence suggests a regulatory connection between cell volume, endoplasmic
      reticulum (ER) export, and stimulated Golgi-to-ER transport. To investigate the
      potential role of protein kinases we tested a panel of protein kinase inhibitors
      for their effect on these steps. One inhibitor, H89, an isoquinolinesulfonamide
      that is commonly used as a selective protein kinase A inhibitor, blocked both ER
      export and hypo-osmotic-, brefeldin A-, or nocodazole-induced Golgi-to-ER
      transport. In contrast, H89 did not block the constitutive ER Golgi-intermediate
      compartment (ERGIC)-to-ER and Golgi-to-ER traffic that underlies redistribution
      of ERGIC and Golgi proteins into the ER after ER export arrest. Surprisingly,
      other protein kinase A inhibitors, KT5720 and H8, as well as a set of protein
      kinase C inhibitors, had no effect on these transport processes. To test whether
      H89 might act at the level of either the coatomer protein (COP)I or the COPII
      coat protein complex we examined the localization of betaCOP and Sec13 in H89
      treated cells. H89 treatment led to a rapid loss of Sec13-labeled ER export sites
      but betaCOP localization to the Golgi was unaffected. To further investigate the
      effect of H89 on COPII we developed a COPII recruitment assay with permeabilized
      cells and found that H89 potently inhibited binding of exogenous Sec13 to ER
      export sites. This block occurred in the presence of guanosine-5'-O-(3
      thio)triphosphate, suggesting that Sec13 recruitment is inhibited at a step
      independent of the activation of the GTPase Sar1. These results identify a
      requirement for an H89-sensitive factor(s), potentially a novel protein kinase,
      in recruitment of COPII to ER export sites, as well as in stimulated but not
      constitutive Golgi-to-ER transport.

PMID- 10930456
TI  - The AP-3 complex required for endosomal synaptic vesicle biogenesis is associated
      with a casein kinase Ialpha-like isoform.
AB  - The formation of small vesicles is mediated by cytoplasmic coats the assembly of
      which is regulated by the activity of GTPases, kinases, and phosphatases. A
      heterotetrameric AP-3 adaptor complex has been implicated in the formation of
      synaptic vesicles from PC12 endosomes (). When the small GTPase ARF1 is prevented
      from hydrolyzing GTP, we can reconstitute AP-3 recruitment to synaptic vesicle
      membranes in an assembly reaction that requires temperatures above 15 degrees C
      and the presence of ATP suggesting that an enzymatic step is involved in the coat
      assembly. We have now found an enzymatic reaction, the phosphorylation of the AP
      3 adaptor complex, that is linked with synaptic vesicle coating. Phosphorylation
      occurs in the beta3 subunit of the complex by a kinase similar to casein kinase
      1alpha. The kinase copurifies with neuronal-specific AP-3. In vitro, purified
      casein kinase I selectively phosphorylates the beta3A and beta3B subunit at its
      hinge domain. Inhibiting the kinase hinders the recruitment of AP-3 to synaptic
      vesicles. The same inhibitors that prevent coat assembly in vitro also inhibit
      the formation of synaptic vesicles in PC12 cells. The data suggest, therefore,
      that the mechanism of AP-3-mediated vesiculation from neuroendocrine endosomes
      requires the phosphorylation of the adaptor complex at a step during or after AP
      3 recruitment to membranes.

PMID- 10930457
TI  - The yeast TEL1 gene partially substitutes for human ATM in suppressing
      hyperrecombination, radiation-induced apoptosis and telomere shortening in A-T
      cells.
AB  - Homozygous mutations in the human ATM gene lead to a pleiotropic clinical
      phenotype of ataxia-telangiectasia (A-T) patients and correlating cellular
      deficiencies in cells derived from A-T donors. Saccharomyces cerevisiae tel1
      mutants lacking Tel1p, which is the closest sequence homologue to the ATM
      protein, share some of the cellular defects with A-T. Through genetic
      complementation of A-T cells with the yeast TEL1 gene, we provide evidence that
      Tel1p can partially compensate for ATM in suppressing hyperrecombination,
      radiation-induced apoptosis, and telomere shortening. Complementation appears to
      be independent of p53 activation. The data provided suggest that TEL1 is a
      functional homologue of human ATM in yeast, and they help to elucidate different
      cellular and biochemical pathways in human cells regulated by the ATM protein.

PMID- 10930458
TI  - The interaction between Ran and NTF2 is required for cell cycle progression.
AB  - The small GTPase Ran is required for the trafficking of macromolecules into and
      out of the nucleus. Ran also has been implicated in cell cycle control,
      specifically in mitotic spindle assembly. In interphase cells, Ran is
      predominately nuclear and thought to be GTP bound, but it is also present in the
      cytoplasm, probably in the GDP-bound state. Nuclear transport factor 2 (NTF2) has
      been shown to import RanGDP into the nucleus. Here, we examine the in vivo role
      of NTF2 in Ran import and the effect that disruption of Ran imported into the
      nucleus has on the cell cycle. A temperature-sensitive (ts) mutant of
      Saccharomyces cerevisiae NTF2 that does not bind to Ran is unable to import Ran
      into the nucleus at the nonpermissive temperature. Moreover, when Ran is
      inefficiently imported into the nucleus, cells arrest in G(2) in a MAD2
      checkpoint-dependent manner. These findings demonstrate that NTF2 is required to
      transport Ran into the nucleus in vivo. Furthermore, we present data that suggest
      that depletion of nuclear Ran triggers a spindle-assembly checkpoint-dependent
      cell cycle arrest.

PMID- 10930459
TI  - Thioredoxin peroxidase is required for the transcriptional response to oxidative
      stress in budding yeast.
AB  - A genetic screen was performed in Saccharomyces cerevisiae to identify mechanisms
      important for the transcriptional activation of genes encoding antioxidant
      proteins. Thioredoxin peroxidase, Tsa1p, of the thioredoxin system, was found to
      be essential for the transcriptional induction of other components of the
      thioredoxin system, TRX2 (thioredoxin) and TRR1 (thioredoxin reductase), in
      response to H(2)O(2). The expression of TRX2 and TRR1 is known to be regulated by
      the transcription factors Yap1p and Skn7p in response to H(2)O(2), and the Tsa1p
      dependent regulation of TRX2 requires the Yap1p/Skn7p pathway. The data suggest
      that expression of components of the thioredoxin system is dependent on the
      activity of Tsa1p in response to H(2)O(2) in a Yap1p/Skn7p-dependent pathway.

PMID- 10930460
TI  - Down-regulation of cell surface receptors is modulated by polar residues within
      the transmembrane domain.
AB  - How recycling receptors are segregated from down-regulated receptors in the
      endosome is unknown. In previous studies, we demonstrated that substitutions in
      the transferrin receptor (TR) transmembrane domain (TM) convert the protein from
      an efficiently recycling receptor to one that is rapidly down regulated. In this
      study, we demonstrate that the "signal" within the TM necessary and sufficient
      for down-regulation is Thr(11)Gln(17)Thr(19) (numbering in TM). Transplantation
      of these polar residues into the wild-type TR promotes receptor down-regulation
      that can be demonstrated by changes in protein half-life and in receptor
      recycling. Surprisingly, this modification dramatically increases the TR
      internalization rate as well ( approximately 79% increase). Sucrose gradient
      centrifugation and cross-linking studies reveal that propensity of the receptors
      to self-associate correlates with down-regulation. Interestingly, a number of
      cell surface proteins that contain TM polar residues are known to be efficiently
      down-regulated, whereas recycling receptors for low-density lipoprotein and
      transferrin conspicuously lack these residues. Our data, therefore, suggest a
      simple model in which specific residues within the TM sequences dramatically
      influence the fate of membrane proteins after endocytosis, providing an
      alternative signal for down-regulation of receptor complexes to the well
      characterized cytoplasmic tail targeting signals.

PMID- 10930461
TI  - EEA1, a tethering protein of the early sorting endosome, shows a polarized
      distribution in hippocampal neurons, epithelial cells, and fibroblasts.
AB  - EEA1 is an early endosomal Rab5 effector protein that has been implicated in the
      docking of incoming endocytic vesicles before fusion with early endosomes.
      Because of the presence of complex endosomal pathways in polarized and
      nonpolarized cells, we have examined the distribution of EEA1 in diverse cell
      types. Ultrastructural analysis demonstrates that EEA1 is present on a subdomain
      of the early sorting endosome but not on clathrin-coated vesicles, consistent
      with a role in providing directionality to early endosomal fusion. Furthermore,
      EEA1 is associated with filamentous material that extends from the cytoplasmic
      surface of the endosomal domain, which is also consistent with a
      tethering/docking role for EEA1. In polarized cells (Madin-Darby canine kidney
      cells and hippocampal neurons), EEA1 is present on a subset of "basolateral-type"
      endosomal compartments, suggesting that EEA1 regulates specific endocytic
      pathways. In both epithelial cells and fibroblastic cells, EEA1 and a transfected
      apical endosomal marker, endotubin, label distinct endosomal populations. Hence,
      there are at least two distinct sets of early endosomes in polarized and
      nonpolarized mammalian cells. EEA1 could provide specificity and directionality
      to fusion events occurring in a subset of these endosomes in polarized and
      nonpolarized cells.

PMID- 10930462
TI  - Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in
      secretion, cell growth, and organelle membrane dynamics.
AB  - The yeast Saccharomyces cerevisiae possesses two genes that encode
      phosphatidylinositol (PtdIns) 4-kinases, STT4 and PIK1. Both gene products
      phosphorylate PtdIns at the D-4 position of the inositol ring to generate
      PtdIns(4)P, which plays an essential role in yeast viability because deletion of
      either STT4 or PIK1 is lethal. Furthermore, although both enzymes have the same
      biochemical activity, increased expression of either kinase cannot compensate for
      the loss of the other, suggesting that these kinases regulate distinct
      intracellular functions, each of which is required for yeast cell growth. By the
      construction of temperature-conditional single and double mutants, we have found
      that Stt4p activity is required for the maintenance of vacuole morphology, cell
      wall integrity, and actin cytoskeleton organization. In contrast, Pik1p is
      essential for normal secretion, Golgi and vacuole membrane dynamics, and
      endocytosis. Strikingly, pik1(ts) cells exhibit a rapid defect in secretion of
      Golgi-modified secretory pathway cargos, Hsp150p and invertase, whereas stt4(ts)
      cells exhibit no detectable secretory defects. Both single mutants reduce
      PtdIns(4)P by approximately 50%; however, stt4(ts)/pik1(ts) double mutant cells
      produce more than 10-fold less PtdIns(4)P as well as PtdIns(4,5)P(2). The
      aberrant Golgi morphology found in pik1(ts) mutants is strikingly similar to that
      found in cells lacking the function of Arf1p, a small GTPase that is known to
      regulate multiple membrane trafficking events throughout the cell. Consistent
      with this observation, arf1 mutants exhibit reduced PtdIns(4)P levels. In
      contrast, diminished levels of PtdIns(4)P observed in stt4(ts) cells at
      restrictive temperature result in a dramatic change in vacuole size compared with
      pik1(ts) cells and persistent actin delocalization. Based on these results, we
      propose that Stt4p and Pik1p act as the major, if not the only, PtdIns 4-kinases
      in yeast and produce distinct pools of PtdIns(4)P and PtdIns(4,5)P(2) that act on
      different intracellular membranes to recruit or activate as yet uncharacterized
      effector proteins.

PMID- 10930463
TI  - Specific sequence motif of 8-Cys repeats of TGF-beta binding proteins, LTBPs,
      creates a hydrophobic interaction surface for binding of small latent TGF-beta.
AB  - Transforming growth factor (TGF)-betas are secreted in large latent complexes
      consisting of TGF-beta, its N-terminal latency-associated peptide (LAP)
      propeptide, and latent TGF-beta binding protein (LTBP). LTBPs are required for
      secretion and subsequent deposition of TGF-beta into the extracellular matrix.
      TGF-beta1 associates with the 3(rd) 8-Cys repeat of LTBP-1 by LAP. All LTBPs, as
      well as fibrillins, contain multiple 8-Cys repeats. We analyzed the abilities of
      fibrillins and LTBPs to bind latent TGF-beta by their 8-Cys repeats. 8-Cys repeat
      was found to interact with TGF-beta1*LAP by direct cysteine bridging. LTBP-1 and
      LTBP-3 bound efficiently all TGF-beta isoforms, LTBP-4 had a much weaker binding
      capacity, whereas LTBP-2 as well as fibrillins -1 and -2 were negative. A short,
      specific TGF-beta binding motif was identified in the TGF-beta binding 8-Cys
      repeats. Deletion of this motif in the 3(rd) 8-Cys repeat of LTBP-1 resulted in
      loss of TGF-beta*LAP binding ability, while its inclusion in non-TGF-beta binding
      3(rd) 8-Cys repeat of LTBP-2 resulted in TGF-beta binding. Molecular modeling of
      the 8-Cys repeats revealed a hydrophobic interaction surface and lack of three
      stabilizing hydrogen bonds introduced by the TGF-beta binding motif necessary for
      the formation of the TGF-beta*LAP - 8-Cys repeat complex inside the cells.

PMID- 10930465
TI  - Syntaxin 17 is abundant in steroidogenic cells and implicated in smooth
      endoplasmic reticulum membrane dynamics.
AB  - The endoplasmic reticulum (ER) consists of subcompartments that have distinct
      protein constituents, morphological appearances, and functions. To understand the
      mechanisms that regulate the intricate and dynamic organization of the
      endoplasmic reticulum, it is important to identify and characterize the molecular
      machinery involved in the assembly and maintenance of the different
      subcompartments. Here we report that syntaxin 17 is abundantly expressed in
      steroidogenic cell types and specifically localizes to smooth membranes of the
      ER. By immunoprecipitation analyses, syntaxin 17 exists in complexes with a
      syntaxin regulatory protein, rsly1, and/or two intermediate compartment SNARE
      proteins, rsec22b and rbet1. Furthermore, we found that syntaxin 17 is anchored
      to the smooth endoplasmic reticulum through an unusual mechanism, requiring two
      adjacent hydrophobic domains near its carboxyl terminus. Converging lines of
      evidence indicate that syntaxin 17 functions in a vesicle-trafficking step to the
      smooth-surfaced tubular ER membranes that are abundant in steroidogenic cells.

PMID- 10930464
TI  - Initiation of nucleolar assembly is independent of RNA polymerase I
      transcription.
AB  - This report examines the distribution of an RNA polymerase I transcription factor
      (upstream binding factor; UBF), pre-rRNA processing factors (nucleolin and
      fibrillarin), and pre-rRNAs throughout mitosis and postmitotic nucleologenesis in
      HeLa cells. The results demonstrate that nucleolin, fibrillarin, and pre-rRNAs
      synthesized at G2/M phase of the previous cell cycle are directly recruited to
      UBF-associated nucleolar organizer regions (NORs) early in telophase before
      chromosome decondensation. Unlike the fusion of prenucleolar bodies to the
      nucleoli, this early recruitment of processing factors and pre-rRNAs is
      independent of RNA polymerase I transcription. In the absence of polymerase I
      transcription, the initial localization of nucleolin, fibrillarin, and pre-rRNAs
      to UBF-associated NORs generates segregated mininucleoli that are similar to the
      larger ones observed in interphase cells grown under the same conditions. Pre
      rRNAs are juxtaposed to UBF-nucleolin-fibrillarin caps that may represent the
      segregated nucleoli observed by electron microscopy. These findings lead to a
      revised model of nucleologenesis. We propose that nucleolar formation at the end
      of mitosis results from direct recruitment of processing factors and pre-rRNAs to
      UBF-associated NORs before or at the onset of rDNA transcription. This is
      followed by fusion of prepackaged prenucleolar bodies into the nucleolus. Pre
      ribosomal ribonucleoproteins synthesized in the previous cell cycle may
      contribute to postmitotic nucleologenesis.

PMID- 10930466
TI  - Nuclear dynamics in Arabidopsis thaliana.
AB  - The nucleus is a definitive feature of eukaryotic cells, comprising twin
      bilamellar membranes, the inner and outer nuclear membranes, which separate the
      nucleoplasmic and cytoplasmic compartments. Nuclear pores, complex macromolecular
      assemblies that connect the two membranes, mediate communication between these
      compartments. To explore the morphology, topology, and dynamics of nuclei within
      living plant cells, we have developed a novel method of confocal laser scanning
      fluorescence microscopy under time-lapse conditions. This is used for the
      examination of the transgenic expression in Arabidopsis thaliana of a chimeric
      protein, comprising the GFP (Green-Fluorescent Protein of Aequorea victoria)
      translationally fused to an effective nuclear localization signal (NLS) and to
      beta-glucuronidase (GUS) from E. coli. This large protein is targeted to the
      nucleus and accumulates exclusively within the nucleoplasm. This article provides
      online access to movies that illustrate the remarkable and unusual properties
      displayed by the nuclei, including polymorphic shape changes and rapid, long
      distance, intracellular movement. Movement is mediated by actin but not by
      tubulin; it therefore appears distinct from mechanisms of nuclear positioning and
      migration that have been reported for eukaryotes. The GFP-based assay is simple
      and of general applicability. It will be interesting to establish whether the
      novel type of dynamic behavior reported here, for higher plants, is observed in
      other eukaryotic organisms.

PMID- 10930467
TI  - Distinct and redundant functions of mu1 medium chains of the AP-1 clathrin
      associated protein complex in the nematode Caenorhabditis elegans.
AB  - In the nematode Caenorhabditis elegans, there exist two micro1 medium chains of
      the AP-1 clathrin-associated protein complex. Mutations of unc-101, the gene that
      encodes one of the micro1 chains, cause pleiotropic effects (). In this report,
      we identified and analyzed the second mu1 chain gene, apm-1. Unlike the mammalian
      homologs, the two medium chains are expressed ubiquitously throughout
      development. RNA interference (RNAi) experiments with apm-1 showed that apm-1 and
      unc-101 were redundant in embryogenesis and in vulval development. Consistent
      with this, a hybrid protein containing APM-1, when overexpressed, rescued the
      phenotype of an unc-101 mutant. However, single disruptions of apm-1 or unc-101
      have distinct phenotypes, indicating that the two medium chains may have distinct
      functions. RNAi of any one of the small or large chains of AP-1 complex (sigma1,
      beta1, or gamma) showed a phenotype identical to that caused by the simultaneous
      disruption of unc-101 and apm-1, but not that by single disruption of either
      gene. This suggests that the two medium chains may share large and small chains
      in the AP-1 complexes. Thus, apm-1 and unc-101 encode two highly related micro1
      chains that share redundant and distinct functions within AP-1 clathrin
      associated protein complexes of the same tissue.

PMID- 10930468
TI  - Analysis of mid1p, a protein required for placement of the cell division site,
      reveals a link between the nucleus and the cell surface in fission yeast.
AB  - mid1 is required for the proper placement of the contractile actin ring for
      cytokinesis at a medial site overlying the nucleus. Here we find that mid1
      protein (mid1p) shuttles between the nucleus and a cortical medial broad band
      during interphase and early mitosis. The position of this broad band, which
      overlies the nucleus, is linked to nuclear position even in cells with displaced
      or multiple nuclei. We identified and created mutations in an NLS and in two crm1
      dependent NES sequences in mid1p. NES mutations caused mid1p accumulation in the
      nucleus and loss of function. An NLS mutations greatly reduced nuclear
      localization but did not perturb cytoplasmic localization or function. mid1p
      localization to the medial broad band was also not dependent on mid1p PH domain
      or microtubule and actin cytoskeletons. Overexpression of mid1p produced ectopic
      cell growth at this band during interphase and abnormal karmellae-like nuclear
      membrane structures. In plo1-1, mid1p formed a medial broad band but did not
      incorporate into a tight ring, suggesting that polo kinase plo1p is required for
      activation of mid1p function. Thus, the mid1p broad band defines a compartment at
      the medial cell surface, whose localization is linked to the position of the
      nucleus, and whose function may be to position the plane of cell division.

PMID- 10930470
TI  - Differential modulation of cadherin-mediated cell-cell adhesion by platelet
      endothelial cell adhesion molecule-1 isoforms through activation of extracellular
      regulated kinases.
AB  - The role of platelet endothelial cell adhesion molecule-1 (PECAM-1) in
      endothelial cell-cell interactions and its contribution to cadherin-mediated cell
      adhesion are poorly understood. Such studies have been difficult because all
      known endothelial cells express PECAM-1. We have used Madin-Darby canine kidney
      (MDCK) cells as a model system in which to evaluate the role of PECAM-1 isoforms
      that differ in their cytoplasmic domains in cell-cell interactions. MDCK cells
      lack endogenous PECAM-1 but form cell-cell junctions similar to those of
      endothelial cells, in which PECAM-1 is concentrated. MDCK cells were transfected
      with two isoforms of murine PECAM-1, Delta15 and Delta14&15, the predominant
      isoforms expressed in vivo. Expression of the Delta15 isoform resulted in
      apparent dedifferentiation of MDCK cells concomitant with the loss of adherens
      junctions, down-regulation of E-cadherin, alpha- and beta-catenin expression, and
      sustained activation of extracellular regulated kinases. The Delta15 isoform was
      not concentrated at cell-cell contacts. In contrast, the Delta14&15 isoform
      localized to sites of cell-cell contact and had no effect on MDCK cell
      morphology, cadherin/catenin expression, or extracellular regulated kinase
      activity. Thus, the presence of exon 14 in the cytoplasmic domain of PECAM-1 has
      dramatic effects on the ability of cells to maintain adherens junctions and an
      epithelial phenotype. Therefore, changes in the expression of exon 14 containing
      PECAM-1 isoforms, which we have observed during development, may have profound
      functional consequences.

PMID- 10930469
TI  - The recycling endosome of Madin-Darby canine kidney cells is a mildly acidic
      compartment rich in raft components.
AB  - We present a biochemical and morphological characterization of recycling
      endosomes containing the transferrin receptor in the epithelial Madin-Darby
      canine kidney cell line. We find that recycling endosomes are enriched in
      molecules known to regulate transferrin recycling but lack proteins involved in
      early endosome membrane dynamics, indicating that recycling endosomes are
      distinct from conventional early endosomes. We also find that recycling endosomes
      are less acidic than early endosomes because they lack a functional vacuolar
      ATPase. Furthermore, we show that recycling endosomes can be reached by apically
      internalized tracers, confirming that the apical endocytic pathway intersects the
      transferrin pathway. Strikingly, recycling endosomes are enriched in the raft
      lipids sphingomyelin and cholesterol as well as in the raft-associated proteins
      caveolin-1 and flotillin-1. These observations may suggest that a lipid-based
      sorting mechanism operates along the Madin-Darby canine kidney recycling pathway,
      contributing to the maintenance of cell polarity. Altogether, our data indicate
      that recycling endosomes and early endosomes differ functionally and
      biochemically and thus that different molecular mechanisms regulate protein
      sorting and membrane traffic at each step of the receptor recycling pathway.

PMID- 10930471
TI  - The internal phosphodiesterase RegA is essential for the suppression of lateral
      pseudopods during Dictyostelium chemotaxis.
AB  - Dictyostelium strains in which the gene encoding the cytoplasmic cAMP
      phosphodiesterase RegA is inactivated form small aggregates. This defect was
      corrected by introducing copies of the wild-type regA gene, indicating that the
      defect was solely the consequence of the loss of the phosphodiesterase. Using a
      computer-assisted motion analysis system, regA(-) mutant cells were found to show
      little sense of direction during aggregation. When labeled wild-type cells were
      followed in a field of aggregating regA(-) cells, they also failed to move in an
      orderly direction, indicating that signaling was impaired in mutant cell
      cultures. However, when labeled regA(-) cells were followed in a field of
      aggregating wild-type cells, they again failed to move in an orderly manner,
      primarily in the deduced fronts of waves, indicating that the chemotactic
      response was also impaired. Since wild-type cells must assess both the increasing
      spatial gradient and the increasing temporal gradient of cAMP in the front of a
      natural wave, the behavior of regA(-) cells was motion analyzed first in
      simulated temporal waves in the absence of spatial gradients and then was
      analyzed in spatial gradients in the absence of temporal waves. Our results
      demonstrate that RegA is involved neither in assessing the direction of a spatial
      gradient of cAMP nor in distinguishing between increasing and decreasing temporal
      gradients of cAMP. However, RegA is essential for specifically suppressing
      lateral pseudopod formation during the response to an increasing temporal
      gradient of cAMP, a necessary component of natural chemotaxis. We discuss the
      possibility that RegA functions in a network that regulates myosin
      phosphorylation by controlling internal cAMP levels, and, in support of that
      hypothesis, we demonstrate that myosin II does not localize in a normal manner to
      the cortex of regA(-) cells in an increasing temporal gradient of cAMP.

PMID- 10930472
TI  - Cell cycle-dependent expression of mammalian E2-C regulated by the anaphase
      promoting complex/cyclosome.
AB  - Progression through mitosis requires the precisely timed ubiquitin-dependent
      degradation of specific substrates. E2-C is a ubiquitin-conjugating enzyme that
      plays a critical role with anaphase-promoting complex/cyclosome (APC/C) in
      progression of and exit from M phase. Here we report that mammalian E2-C is
      expressed in late G(2)/M phase and is degraded as cells exit from M phase. The
      mammalian E2-C shows an autoubiquitinating activity leading to covalent
      conjugation to itself with several ubiquitins. The ubiquitination of E2-C is
      strongly enhanced by APC/C, resulting in the formation of a polyubiquitin chain.
      The polyubiquitination of mammalian E2-C occurs only when cells exit from M
      phase. Furthermore, mammalian E2-C contains two putative destruction boxes that
      are believed to act as recognition motifs for APC/C. The mutation of this motif
      reduced the polyubiquitination of mammalian E2-C, resulting in its stabilization.
      These results suggest that mammalian E2-C is itself a substrate of the APC/C
      dependent proteolysis machinery, and that the periodic expression of mammalian E2
      C may be a novel autoregulatory system for the control of the APC/C activity and
      its substrate specificity.

PMID- 10930473
TI  - Three dimensional structure of the seventh transmembrane helical domain of the G
      protein receptor, rhodopsin.
AB  - PURPOSE: The three dimensional structure of a peptide comprising the sequence of
      the seventh transmembrane segment of the G-protein coupled receptor, rhodopsin,
      was determined in solution. METHODS: The sequence of the seventh transmembrane
      segment of rhodopsin, which contains the NPxxY sequence that is highly conserved
      among G-protein coupled receptors and lys296 that forms the Schiff base with the
      retinal, was synthesized by solid phase peptide synthesis. The three dimensional
      structure was determined in solution by high-resolution nuclear magnetic
      resonance (NMR). RESULTS: The structure revealed a helix-break-helix motif for
      this sequence. Two families of structures were observed which differed in the
      angle between the two helical segments. The sequence of this transmembrane
      segment overlapped significantly the sequence of a peptide from the carboxyl
      terminal of rhodopsin, the structure of which was solved previously. The
      redundant sequence formed a helix in both peptides. It was therefore possible to
      superimpose the redundant sequence of both peptides and construct a structure for
      rhodopsin encompassing residues 291-348. CONCLUSIONS: This structure reveals
      locations of the lys296 and the acylation sites of rhodopsin that are consistent
      with the known biochemistry of this receptor. This segmentation approach to
      membrane protein structure provides important structural information in the
      absence of an X-ray crystal structure of rhodopsin. The approach is expected to
      be useful for other G-protein coupled receptors.

PMID- 10930475
TI  - DDRT-PCR: use of agarose gels for detection of amplified products.
AB  - The present study focuses on the detection of differentially expressed genes in
      migrating (healing) and nonmigrating (normal) corneal epithelium on agarose gel
      using a modified procedure of differential display reverse transcriptase
      polymerase chain reaction (DDRT-PCR). Rabbit corneal epithelial organ cultures
      were used to obtain nonmigrating and migrating samples. RNA was extracted using
      Trizol LS reagent. PCR was modified in order to allow detection of amplified
      products on 3% agarose gel with ethidium bromide staining. Products were also
      resolved on 6% denaturing polyacrylamide-urea gels and observed by silver
      staining. Agarose gels showed two prominent bands that were heavily expressed in
      the 458 bp and 587 bp region of the nonmigrating samples. In addition light bands
      were visible in the region corresponding to 234 bp and 450 bp. In the migrating
      samples, two light bands were visible in the region of 267 bp and 300 bp. Eight
      amplicons, six in the nonmigrating corneal epithelial sample and two in the
      migrating corneal epithelial samples, were also found to be differentially
      expressed when products were run on 6% denaturing polyacrylamide-urea gels. Thus,
      DDRT-PCR products can be detected on agarose gels and prove very helpful and
      economical in the initial studies of DDRT-PCR.

PMID- 10930476
TI  - The surgical balancing act.

PMID- 10930474
TI  - Effect of latrunculin-A on morphology and actin-associated adhesions of cultured
      human trabecular meshwork cells.
AB  - PURPOSE: Determine the effects of the actin cytoskeleton disrupting compound
      latrunculin-A (LAT-A) on morphology, cytoskeleton, and cellular adhesions of
      cultured human trabecular meshwork (HTM) cells. METHODS: HTM cells were cultured
      to high confluence with endothelial-like morphology and treated with LAT-A at
      different doses and duration. Topography of living cells was evaluated by
      videomicroscopy. Distribution and organization of the actin-based cytoskeleton,
      vinculin- and paxillin-containing focal contacts, and beta-catenin-rich
      intercellular adhesions were determined by immunofluorescence and digital
      microscopy. RESULTS: LAT-A induced pronounced but highly reversible rounding of
      HTM cells, intercellular separation, and disruption of actin filaments. beta
      catenin-rich intercellular adherens junctions were particularly sensitive to LAT
      A. Vinculin- and paxillin-containing focal contacts were only partially affected
      and appeared to be more resistant to the drug than the intercellular
      interactions. CONCLUSIONS: The increase in outflow facility in the living primate
      eye induced by LAT-A may be due to the disorganization and disruption of the
      actin cytoskeleton and its associated cellular adhesions in the trabecular
      meshwork.

PMID- 10930477
TI  - Clinical presentation of mucin-secreting tumors of the pancreas.
AB  - BACKGROUND: Pancreatitis and jaundice secondary to ductal obstruction are common
      in intraductal papillary mucinous tumors (IPMT) of the pancreas. However, the
      incidence and severity of the complications of obstruction are not well
      documented. The aim of the study was to investigate the clinical presentation and
      outcome of 10 patients with IPMT. METHODS: All cases of IPMT diagnosed between
      1994 and 1999 were reviewed. RESULTS: Four of the 10 patients developed severe
      acute illness with systemic complications resulting from ductal obstruction.
      Three suffered acute cholangitis with sepsis, and 1 developed necrotizing
      pancreatitis and ARDS. There was 1 postoperative death in a patient with
      adenocarcinoma. All other patients are alive and well with a median follow-up of
      26 months (survival 90%). CONCLUSIONS: Pancreatic or common bile duct obstruction
      in IPMT may result in acute, life-threatening disease. Aggressive surgical
      therapy is warranted before development of complications of ductal obstruction or
      progression of tumor occurs.

PMID- 10930478
TI  - Computed tomography severity index is a predictor of outcomes for severe
      pancreatitis.
AB  - BACKGROUND: In a small group of patients with acute pancreatitis, Balthazar and
      Ranson demonstrated the applicability of computed tomography (CT) criteria to
      predict mortality. Building upon their work with a larger group of patients with
      acute pancreatitis, we set out not only to demonstrate that the CT severity index
      can predict death, but also length of hospital stay and need for necrosectomy.
      METHODS: We reviewed all patients admitted to our hospital in the years 1992 to
      1997 with a primary diagnosis of acute pancreatitis. Entrance criteria required
      that a CT scan had been performed during the hospitalization. The index CT scan
      was used to determine a CT severity index (the CTSI of Balthazar and Ranson).
      Outcomes measured were death, length of stay (LOS), and need for necrosectomy
      (NEC). Statistical analysis was performed using Fisher's exact and chi-square
      tests where appropriate. RESULTS: Between the years 1992 to 1997, 886 patients
      had 1,774 admissions for acute pancreatitis, of which 268 had a CT scan performed
      and were entered into our study. These 268 patients had a mean age of 57 years, a
      mean LOS of 16 days (1 to 118), and a mean CTSI of 3.9 (0 to 10). Overall
      mortality was 4% (n = 11). A CTSI >5 significantly correlated with death (P =
      0.0005), prolonged hospital stay (P <0.0001), and need for necrosectomy (P
      <0.0001). Patients with a CTSI >5 were 8 times more likely to die, 17 times more
      likely to have a prolonged hospital course, and 10 times more likely to undergo
      necrosectomy than their counterparts with CT scores <5. CONCLUSIONS: These data
      show that the CTSI is an applicable and comparable predictor of outcomes in
      severe pancreatitis.

PMID- 10930479
TI  - Mesohepatectomy.
AB  - BACKGROUND: Formal anatomic (lobar) or extended hepatectomies are recommended for
      liver malignancies located centrally within the liver (Couinaud's segments IVA,
      IVB, V, and VIII). Mesohepatectomy, resection of central hepatic segments and
      leaving the right and left segments in situ, removes large central tumors
      preserving more functioning liver tissue than either extended left or right
      hepatectomy. Mesohepatectomy is a seldom used, technically demanding procedure,
      and its application is yet to be defined. METHODS: Medical charts of 244
      consecutive liver resection patients were reviewed retrospectively. Eighteen
      patients were treated with mesohepatectomy. Six patients had metastatic liver
      tumor (MLT), 11 had hepatocellular carcinoma (HCC), and 1 had gallbladder
      adenocarcinoma. The operative results were compared with groups of patients
      treated by lobar hepatectomy (n = 71) and extended left or right hepatectomy (n =
      43). RESULTS: The mean mesohepatectomy operative time was 238 versus 304 minutes
      in the extended group. Inflow occlusion mean time was longer in the
      mesohepatectomy group than in extended procedures, 45 versus 39 minutes (P = not
      significant). Comparing the extended hepatectomy group, the mesohepatectomy group
      had a mean operative estimated blood loss 914 cc versus 1628 cc (P <0.01),
      postoperative hospital stay 9 versus 16 days (P = 0.054) and volume of resected
      liver 560cc versus 1500cc (P <0.01) respectively. The late complication rate was
      lower in the mesohepatectomy group than in the extended group and was comparable
      to the lobar hepatectomy group (P = 0.05). CONCLUSIONS: Despite its technical
      demands, mesohepatectomy should be considered as an alternative to extended
      hepatectomy for selected patients with primary and secondary hepatic tumors
      localized in middle liver segments, as its complication rate, postoperative
      recovery, and preserved liver tissue compare favorably with extended hepatic
      resection.

PMID- 10930480
TI  - The microbiology of necrotizing soft tissue infections.
AB  - OBJECTIVE: A large number of necrotizing soft tissue infections (NSTI) treated at
      a single institution over an 8-year period were analyzed with respect to
      microbial pathogens recovered, treatment administered, and outcome. Based on this
      analysis, optimal empiric antibiotic coverage is proposed. METHODS: A
      retrospective chart review of all patients with documented NSTI was conducted.
      Microbiologic variables were tested for impact on outcome using Fisher's exact
      test and multivariate analysis by logistic regression. RESULTS: Review of the
      charts of 198 patients with documented NSTI revealed 182 patients with sufficient
      microbiologic information for analysis. These 182 patients grew an average of 4.4
      microbes from original wound cultures, although a single pathogen was responsible
      in 28 patients. Eighty-five patients had combined aerobic and anaerobic growth,
      the most common organisms being, in order, Bacteroides species, aerobic
      streptococci, staphylococci, enterococci, Escherichia coli, and other gram
      negative rods. Clostridial growth was common but did not affect mortality unless
      associated with pure clostridial myonecrosis. Mortality was affected by the
      presence of bacteremia, delayed or inadequate surgery, and degree of organ system
      dysfunction on admission. CONCLUSIONS: NSTI are frequently polymicrobial and
      initial antibiotic coverage with a broad-spectrum regimen is warranted. The
      initial regimen should include agents effective against aerobic gram-positive
      cocci, gram-negative rods, and a variety of anaerobes. The most common organisms
      not covered by initial therapy were enterococci. All wounds should be cultured at
      initial debridement, as changes in antibiotic coverage are frequent once isolates
      are recovered.

PMID- 10930481
TI  - Interferon-based adjuvant chemoradiation therapy improves survival after
      pancreaticoduodenectomy for pancreatic adenocarcinoma.
AB  - BACKGROUND: Based on a 2-year survival of 43%, the Gastrointestinal Tumor Study
      Group (GITSG) recommended adjuvant 5-FU-based chemoradiation for resected
      patients with adenocarcinoma of the pancreatic head. Here we report improved
      survival over the GITSG protocol with a novel adjuvant chemoradiotherapy based on
      interferon-alpha (IFNalpha). METHODS: From July 1993 to September 1998, 33
      patients with adenocarcinoma of the pancreatic head underwent
      pancreaticoduodenectomy (PD) and subsequently went on to adjuvant therapy (GITSG
      type, n = 16) or IFNalpha-based (n = 17) typically given between 6 and 8 weeks
      after surgery. The latter protocol consisted of external-beam irradiation at a
      dose of 4,500 to 5,400 cGy (25 fractions per 5 weeks) and simultaneous three-drug
      chemotherapy consisting of (1) continuous infusion 5-FU (200 mg/m2 per day); (2)
      weekly intravenous bolus cisplatin (30 mg/m2 per day); and (3) IFNalpha (3
      million units subcutaneously every other day) during the 5 weeks of radiation.
      This was then followed by two 6-week courses of continuous infusion 5-FU (200
      mg/m2 per day, given weeks 9 to 14 and 17 to 22). Risk factors for recurrence and
      survival were compared for the two groups. RESULTS: A more advanced tumor stage
      was observed in the IFNalpha-treated patients (positive nodes and American Joint
      Committee on Cancer [AJCC] stage III = 76%) than the GITSG group (positive nodes
      and stage III = 44%, P = 0.052). The 2-year overall survival was superior in the
      IFNalpha cohort (84%) versus the GITSG group (54%). With a mean follow-up of 26
      months in both cohorts, actuarial survival curves significantly favored the
      IFNalpha group (P = 0.04). CONCLUSIONS: With a limited number of patients, this
      phase II type trial suggests better survival in the interferon group as compared
      with the GITSG group even though the interferon group was associated with a more
      extensive tumor stage. The 2-year survival rate in the interferon group is the
      best published to date for resected pancreatic cancer. The interferon/cisplatin/5
      FU-based adjuvant chemoradiation protocol appears to be a promising treatment for
      patients who have undergone PD for adenocarcinoma of the pancreatic head.

PMID- 10930482
TI  - Laparoscopic common duct exploration in the management of choledocholithiasis.
AB  - BACKGROUND: Optimal treatment strategies for addressing common duct stones at
      laparoscopic cholecystectomy remain controversial. The study presents the
      authors' experience with laparoscopic common bile duct exploration (LCBDE).
      METHODS: A retrospective review was performed of 71 LCBDEs performed over 5 years
      using either transcystic duct flushing and mechanical techniques, transcystic
      duct basket retreival techniques, or laparoscopic choledochotomy. RESULTS:
      Laparoscopic CBDE resulted in ductal clearance in 61 of 71 (85%) cases with only
      1 case of unsuspected retained common duct stones and only 1 major complication.
      Review of the cases that did not result in common duct clearance suggests that
      the success rate of laparoscopic CBDE could be increased. CONCLUSIONS:
      Laparoscopic CBDE is an effective treatment for concurrent gallstones and common
      duct stones and avoids the potential morbidity of an endoscopic sphincterotomy.
      General surgeons with adequate training and experience can perform laparoscopic
      CBDE safely and effectively.

PMID- 10930483
TI  - Laparoscopic versus open appendectomy.
AB  - BACKGROUND: Laparoscopic appendectomy is commonly performed and has been presumed
      to offer economic benefits similar to those of laparoscopic cholecystectomy. This
      study was done to examine that premise. METHODS: Two surgical groups contributed
      consecutively operated patients with a clinical diagnosis of appendicitis. One
      group did all appendectomies open and the other group did them laparoscopically.
      Hospital expenses were compared using a single billing formula. Hospital length
      of stay, time to return to work, and complications were analyzed. RESULTS:
      Operating room times were longer for the laparoscopic group, median 80 minutes,
      versus median 50 minutes for the open group. Hospital length of stay and return
      to work were the same, median 1 day and median 10 days, respectively. Wound
      complications were less common in the laparoscopic group, 0 of 30, than in the
      open group, 3 of 18; however, there was 1 intra-abdominal abscess in the
      laparoscopic group. Median cost of the laparoscopic group was $2,915 versus
      $1,747 for the open group. CONCLUSIONS: Laparoscopic appendectomy is more
      expensive than appendectomy but does not reduce hospital length of stay nor
      change the time to return to work; however, wound complications are less common.

PMID- 10930484
TI  - A prospective trial of computed tomography and ultrasonography for diagnosing
      appendicitis in the atypical patient.
AB  - BACKGROUND: The surgical diagnosis of acute appendicitis is customarily made on
      clinical grounds alone using history, physical examination, and white blood cell
      count. In the atypical patient, ie, the patient with prolonged symptoms,
      inconsistent history, or misleading physical examination, diagnostic studies
      should be helpful in establishing the appropriate diagnosis. Computed tomography
      (CT) scan and ultrasonography (US) have demonstrated utility in diagnosing
      appendicitis but have not been studied in the atypical patient population.
      METHODS: A retrospective review of 500 consecutive appendectomy patients, coupled
      with a review of the literature, resulted in the development of an algorithm to
      help the medical physician to differentiate the atypical patient requiring an
      imaging study from those requiring immediate surgical consultation. This patient
      population was entered into a prospective, randomized study of CT scan or US
      examination. RESULTS: Between May 1997 and May 1999, 106 patients were enrolled
      in the study; 17 were later excluded from the study because of typical
      presentation and direct admission to surgery without diagnostic imaging. Forty
      nine patients were randomly assigned to CT scan and 40 to US examination. CT scan
      was 100% specific and 97% sensitive (P = 0.018). US was 90% specific and 76%
      sensitive. Based on the results of these imaging studies, 70 of the study
      patients underwent exploration for suspected appendicitis or other acute
      inflammatory process. CONCLUSION: A subset of patients presenting with possible
      acute appendicitis has been identified that should benefit from imaging of the
      appendix prior to surgical consultation. For this group, CT scan appears superior
      to abdominal and pelvic US in terms of diagnostic accuracy and reliability. With
      this approach, a low incidence of negative laparotomies was achieved.

PMID- 10930485
TI  - Patient satisfaction after carotid endarterectomy using a selective policy of
      local anesthesia.
AB  - BACKGROUND: Patient satisfaction after carotid endarterectomy has not been
      specifically studied or reported. Results of carotid endarterectomy using either
      local or general anesthesia have been widely reported, and outcomes are not
      significantly different for either technique. Patient satisfaction data were
      obtained in order to determine whether patients preferred one method of
      anesthesia over another. Data regarding outcome may be added to the surgical
      literature as benchmark data when comparing operative carotid endarterectomy to
      newer techniques. METHODS: During a 30-month period, 186 consecutive carotid
      endarterectomies were performed on 169 patients by a single surgeon with
      assistance from senior surgical residents. All patients were offered local
      anesthesia using a cervical block technique with intraoperative supplementation.
      Patients for whom local anesthesia was inappropriate or who declined were
      operated on using general endotracheal anesthesia. Results of operation were
      tabulated including indication for operation, method of anesthesia,
      intraoperative and postoperative complications, and mortality, and completion of
      a patient satisfaction survey form either on postoperative visit or by telephone
      questionnaire. RESULTS: Of 169 patients who underwent carotid endarterectomy, 151
      (89%) completed the satisfaction survey form. One hundred fourteen (62%) had
      local anesthesia and 71 patients (38%) had general anesthesia. There was 1 stroke
      (0.5%) and 1 death (0.5%) in the series. Perioperative complications including
      temporary cranial nerve injury, neck hematoma, myocardial infarction, and
      restenosis were noted and not significantly different in either the general
      anesthesia or local anesthesia group. Patient satisfaction data including
      intraoperative discomfort, postoperative pain, attentiveness of the operating
      room staff, and length of stay were all tabulated. There was no statistically
      significant difference in satisfaction between the general anesthesia group and
      the local anesthesia group (chi-square and Fisher's exact test). Additionally,
      satisfaction with the procedure was extremely high. CONCLUSIONS: Patient outcome
      and perception of pain and recovery were not statistically significantly
      different in patients undergoing carotid endarterectomy using local anesthesia
      compared with general anesthesia. Overall patient satisfaction was extremely
      high. Patients should be offered carotid endarterectomy using an anesthesia
      technique with which the surgeon and patients are both comfortable, having
      confidence that the outcome is not related to anesthesia technique and that
      patients will be highly satisfied.

PMID- 10930486
TI  - Sentinel node biopsy and internal mammary lymphatic mapping in breast cancer.
AB  - BACKGROUND: Currently outer quadrant breast tumors are not felt to have
      significant drainage to the internal mammary nodal chain. We evaluated the
      incidence of internal mammary sentinel nodes (IMSN) found with lymphoscintigraphy
      for all breast quadrants. METHODS: Eighty women were prospectively studied by
      technitium-sulfur colloid injection, nuclear medicine imaging, and intraoperative
      gamma probe identification of sentinel nodes. IMSN detected were surgically
      removed. RESULTS: Ten of 80 ( 12%) patients had IMSN identified in addition to
      axillary sentinel nodes (AXSN). Four tumors were located medially, 6 (60%) were
      in the outer quadrants. Metastatic disease was present in 3 of 10 women. Patients
      with positive IMSN also had positive AXSN. CONCLUSIONS: Patients undergoing
      lymphatic mapping for the management of breast cancer should have radiolabelled
      tracer and gamma probe sentinel node identification regardless of tumor location
      in the breast.

PMID- 10930487
TI  - Target-specific rib biopsy using the gamma probe.
AB  - BACKGROUND: Intraoperative localization of rib abnormalities identified on bone
      scan can be deceptively difficult. Previously used techniques have had limited
      sensitivity and accuracy. The gamma probe can help localize these bone scan "hot
      spots." METHODS: Over the past 17 months, 5 patients underwent gamma-probe
      directed limited rib resections following intravenous administration of Tc99m
      MDP. Three patients required biopsies for suspected malignancy, and the other 2
      underwent therapeutic resections for pain. The device was easy to work with
      following minimal training. RESULTS: Localization was excellent, limiting the
      extent of surgery needed. Comparison with rib counting and preoperative bone scan
      localization showed a discrepancy of up to 13 cm. Sensitivity and accuracy were
      each 100%. CONCLUSIONS: The gamma probe offers a simple and significant advance
      in the performance of rib biopsies for nonpalpable lesions.

PMID- 10930488
TI  - Outcomes of laparoscopic antireflux procedures.
AB  - BACKGROUND: Laparoscopy has increased the number of patients undergoing operative
      correction of gastroesophageal reflux disease (GERD). Symptom improvement has
      been most commonly reported as the means to assess operative outcome. We compared
      symptomatic outcome to postoperative pH testing at short-term follow-up to
      determine the accuracy of clinical assessment at predicting whether acid exposure
      would be normal or abnormal. METHODS: Of 640 patients who had antireflux surgery
      between 1993 and 1999, 228 (36%) agreed to repeat manometry and 24-hour pH
      monitoring 8 to 12 weeks postoperatively and are the subject of this study.
      Symptom resolution was assumed if the frequency was less than once per week.
      Normal acid exposure consisted of a distal esophageal pH below 4 less than 4% of
      the time and a DeMeester composite score less than 14.7. Accuracy of symptom
      scoring was calculated using acid exposure as the standard. RESULTS: The primary
      symptom was improved in 93% of the 228 patients. Acid exposure was reduced from a
      preoperative DeMeester score of 71 to 16 (P <0.05). Eighty percent of patients
      had normalization of acid exposure postoperatively. Heartburn was the only
      symptom to have a significant correlation with acid exposure in the postoperative
      period (P <0.05). Heartburn resolved in 181 patients, 168 of whom had normal acid
      exposure (true negative). Thirty-eight patients without symptoms had abnormal
      acid exposure (false negative). Nine patients had persistent heartburn with
      abnormal acid exposure (true positive) whereas 13 patients had persistent
      heartburn with normal acid exposure (false positive). Thus, the positive
      predictive value of heartburn was 43%, the negative predictive value was 82%, and
      the overall accuracy was 78%. CONCLUSIONS: Operative treatment improves both the
      symptoms of GERD and the degree of acid exposure as measured by pH monitoring.
      The most accurate symptom for predicting acid exposure in the postoperative
      period is heartburn. Although the absence of heartburn postopertively is fairly
      reliable at predicting normal acid exposure on pH testing, the presence of
      heartburn warrants postoperative pH monitoring, as more than half of these
      patients will have normal acid exposure.

PMID- 10930489
TI  - Correlation between physiological assessment and outcome after liver
      transplantation.
AB  - BACKGROUND: Critical shortages of organ donors for transplantation require
      appropriate utilization of this scarce resource. The purpose of this study was to
      assess whether use of physiological parameters of preliver transplant recipients
      is helpful in determining eventual outcome. METHODS: Between October 1989 and
      June 1999, 215 liver transplants were performed on 199 patients at the Vancouver
      Hospital nad Health Sciences Centre. Thirty-one patients undergoing
      transplantation between May 1993 and June 1994 were retrospectively evaluated to
      obtain a minimum 5-year follow-up. Variables examined included pretransplant
      activation status (status 1, at home; status 2, hospitalized; status 3, admitted
      to intensive care; status 4, mechanical ventilation), simplified acute
      physiological score (SAPS), Acute Physiology, Age, and Chronic Health Evaluation
      (APACHE) II, and APACHE III scores at the time of transplantation. The scores
      were correlated to posttransplant mortality and functional outcome. RESULTS: The
      5-year mortality for status 1 patients was 14.3% versus 30% for patients listed
      as status 2 or greater (P = not significant). There were no significant
      differences in any of the physiological scoring assessments with regard to
      posttransplant mortality or functional assessment. Of the surviving patients, 18
      of 22 who were employed, in school, or active at home pretransplant returned to
      their pretransplant activity. CONCLUSIONS: Detailed physiological scoring systems
      are no more accurate in predicting outcome after liver transplant than current
      listing status parameters.

PMID- 10930490
TI  - Immunohistochemical analysis of primary breast tumors and tumor-draining lymph
      nodes by means of the T-cell costimulatory molecule OX-40.
AB  - OBJECTIVES: The OX-40 receptor (OX-40R/CD134) is expressed primarily on activated
      CD4(+) ("helper") T cells. We have previously reported the presence of OX-40(+) T
      cells in head and neck cancer and melanoma, where they appear to be restricted to
      tumor compartments (primary tumor infiltrating lymphocytes [TILs] and draining
      lymph node cells) and therefore may represent the tumor antigen-specific CD4(+) T
      cells. METHODS: In order to determine the degree of OX-40R expression, and any
      relationship with the presence of tumor cells (lobular and/or infiltrating ductal
      carcinoma), 45 archived paraffin-embedded breast primary tumors and their
      associated draining (axillary) lymph nodes were retrospectively analyzed using
      standard immunohistochemical techniques. RESULTS: Seven of 45 primary tumors
      (16%) and 7 of 29 with lympocytic infiltrates (24%) were noted to have elevated
      levels of OX-40R(+) lymphocytes within the tumor specimens, including 2 of 4
      specimens thought to have only "pure" ductal carcinoma in situ (DCIS). No OX
      40R(+) lymphocytes were noted in normal breast tissue. Twenty-one (43%) patients
      had axillary metastases at the time of resection. High levels of OX-40R
      expression was seen in 9 (45%) of these 21 axillary node specimens, whereas no
      such staining was seen in the node-negative specimens (P <0.001). Furthermore, in
      a patient thought to be without axillary disease, several subcapsular single-cell
      metastases were retrospectively discovered near a lone cluster of OX-40R(+)
      lymphocytes. In general, visual inspection showed OX-40R(+) T cells to be in
      close proximity to tumor and often in direct contact with metastatic cells.
      CONCLUSIONS: The OX-40R is upregulated on lymphocytes within tumor draining lymph
      nodes, and these lymphocytes are specifically localized around tumor deposits.
      These data imply that OX-40R immunostaining may be useful for both determination
      of occult involvement of lymph nodes by tumor and for identification of potential
      candidates for future OX-40 based immunotherapy.

PMID- 10930491
TI  - A comparison of complementary therapy use between breast cancer patients and
      patients with other primary tumor sites.
AB  - BACKGROUND: Interest in complementary therapies in the United States is rising.
      We sought to characterize the use of complementary therapies among our cancer
      patients in our community and analyze differences in use between patients with
      breast versus those with other primary tumor sites. METHODS: A survey of 1,935
      randomly selected patients from the tumor registry was performed. A questionnaire
      was mailed to 935 breast cancer patients and 1,000 patients with other primary
      site diagnoses. RESULTS: There were 617 responses (288 breast, 329 other).
      Seventy-five patients (75%) reported use of a complementary modality. Top
      therapies used were nutrition (63%), massage (53%), and healing herbs (44%). The
      most common reason for use, immune modulation (73%), was similar in both groups.
      Therapy was used consistently by 84% of breast patients versus 66% of others (P =
      0.003). CONCLUSION: A significant number of cancer patients are using
      complementary therapies. Breast cancer patients are far more likely to be
      consistent users compared with other tumor sites.

PMID- 10930492
TI  - An analysis of breast cancer surgery after free transverse rectus abdominis
      myocutaneous (TRAM) flap reconstruction.
AB  - BACKGROUND: Breast reconstruction is currently offered on a more routine basis to
      patients after mastectomy for breast cancer. This paper analyzes the outcomes of
      breast cancer surgery, and the results and effects of breast reconstruction using
      free TRAM flaps. METHODS: A retrospective review of 75 consecutive patients who
      had free transverse rectus abdominis myocutaneous (TRAM) flap breast
      reconstruction after breast cancer surgery was performed. A total of 92 free TRAM
      flaps were performed on 75 patients in Victoria, British Columbia, from January
      1992 to May 1999. Thirty-three patients (44%) underwent primary breast cancer
      surgery and an immediate reconstruction (7 bilateral and 27 unilateral) and 42
      patients (56%) had delayed reconstruction (10 bilateral and 32 unilateral).
      RESULTS: Twenty- one patients (28%) had stage 0 disease, 20 (26.7%) had stage I
      disease, 17 (22.7%) had stage IIA disease, 12 (15%) had stage IIB disease, and 4
      (5.3%) had stage IIIA disease. In 1 patient the stage of disease was unknown. The
      mean patient age was 49.4 years (range 33 to 73). Of the patients undergoing
      immediate reconstruction 3 had postoperative chemotherapy and 1 had postoperative
      radiotherapy. Three patients had combined chemoradiotherapy. In none of these
      cases was the adjuvant therapy delayed by the reconstructive surgery. Overall
      mean follow-up time from cancer diagnosis was 56.8 months and from the time of
      TRAM flap reconstruction, 36.7 months. To date, 5 recurrences have been detected
      (6.6%). Mean time between reconstruction and detection of recurrence was 22.8
      months. Detection of recurrence was achieved clinically and was not impaired in
      any of the cases by the presence of the free flap. Patient satisfaction was
      assessed via a telephone survey, with 93% of patients pleased with the cosmetic
      results of their surgery. CONCLUSIONS: For those patients with breast cancer
      requiring mastectomy, free TRAM flap reconstruction is a safe, cosmetically
      acceptable surgical alternative that impairs neither effective breast cancer
      surgery nor detection of recurrent disease.

PMID- 10930493
TI  - Formula for surgical practice resuscitation in an academic medical center.
AB  - BACKGROUND: Managing patient referrals for surgical consultation in an academic
      practice has traditionally emphasized clinical rather than service expertise.
      However, assuring both efficiency and accuracy in the initial consultation have
      become critical early measures of quality care. METHODS: In partnership with the
      academic medical center administration, current practice was analyzed.
      Performance and communication standards were established around an ideal patient
      experience. A new ambulatory consultation process was developed; and flowcharting
      methods for resource allocation, statistical process control, and pre-visit data
      collection were used to reduce patient administrative time. Automated referral
      reports engaged referring physicians throughout the consultation. RESULTS:
      Accurate insurance and referral authorization have been provided for all
      patients, including the 4% who are underinsured. Patient, provider, and referring
      physician satisfaction has increased significantly. Staff time investment has
      progressively declined from 52 +/- 11 (95% confidence) minutes to 34 +/- 10
      minutes for most patients. Realignment of tasks has reduced the administrative
      time spent by the patient by 32% without compromising clinical time. New patient
      volume increased by 29% per year, maintaining regional market share. CONCLUSIONS:
      Expertise in the process of consultation delivery is feasible and will be
      increasingly critical to the survival of academic surgical practice in a
      competitive market.

PMID- 10930494
TI  - Office-based wire-guided open breast biopsy under local anesthesia is accurate
      and cost effective.
AB  - BACKGROUND: Mammographic abnormalities found to be malignant by stereotactic
      biopsy still require a wire-guided biopsy (WGB) in most cases. We have previously
      described a simplified method of WGB that allows the procedure to be done with a
      minimum of dissection and under local anesthesia in the office setting. We
      hypothesized that this procedure can be used to produce cost-effective, office
      based breast preservation therapy (BPT). METHODS: We reviewed our recent
      experience with this WGB method to determine applicability and accuracy in the
      office setting. A cost-effectiveness analysis was also performed to determine
      potential charge reductions when this method is used to avoid operating room (OR)
      usage for either lumpectomy or lumpectomy plus sentinel lymph node biopsy (SLNB).
      RESULTS: Of the 164 biopsies reviewed, 114 (70%) were performed in the office
      setting under local anesthesia and 50 (30%) were performed in the OR. The most
      common reasons for choosing the OR setting included performance of biopsy during
      an unrelated procedure requiring the OR (16 cases), patient preference (12), deep
      lesions (6), and the inability of the patient to cooperate with local anesthesia
      (5). The complication rates were similar between the two settings (7% for office
      based and 4% for OR; P = 0.697), and in neither setting were any lesions missed.
      A cost-effectiveness analysis using our Current Procedure Terminology (CPT)-based
      charges revealed a potential per-case charge reduction of $4,632 for office-based
      lumpectomy and $4306 for office-based lumpectomy/SLNB, using our method of WGB
      and local anesthesia, compared with the OR setting. CONCLUSIONS: Office-based WGB
      using our previously described method is accurate and can be applied to at least
      70% of patients. Based on the favorable results of our cost analysis and rising
      support for SLNB, we anticipate increased utilization of the clinic setting and
      local anesthesia for BPT in the future.

PMID- 10930496
TI  - Long-term trends in occupational exposure: Are they real? What causes them? What
      shall we do with them?

PMID- 10930495
TI  - Association of fungal infection and increased mortality in liver transplant
      recipients.
AB  - BACKGROUND: Invasive fungal infection is associated with increased morbidity and
      mortality following orthotopic liver transplantation (OLTx). Understanding the
      risk factors associated with fungal infection may facilitate identification of
      high-risk patients and guide appropriate initiation of antifungal therapy.
      OBJECTIVES: The aim of this study was to determine the incidence of fungal
      infections, identify the most common fungal pathogens, and determine the risk
      factors associated with fungal infections and mortality in OLTx recipients.
      METHODS: Medical records from 96 consecutive OLTx in 90 American veterans (88
      males, 2 females; mean age 48 years, range 32 to 67) performed from January 1994
      to December 1997 were retrospectively reviewed for fungal infection in the first
      120 days after transplantation. Infection was defined by positive cultures from
      either blood, urine (<105 CFU/mL), cerebrospinal or peritoneal fluid, and/or deep
      tissue specimens. Superficial fungal infection and asymptomatic colonization were
      excluded from study. All patients received cyclosporine, azathioprine, and
      prednisone as maintenance immunosuppressive therapy. Fungal prophylaxis consisted
      of oral clotrimazole (10 mg) troches, five times per day during the study period.
      RESULTS: Thirty-five patients (38%) had documented infection with one or more
      fungal pathogens, including Candida albicans (25 of 35; 71%), C torulopsis (7 of
      35; 20%), C tropicalis (2 of 35; 6%), non-C albicans (2 of 35; 6%), Aspergillus
      fumigatus (4 of 35; 11%), and Cryptococcus neoformans (1 of 35; 3%). The crude
      survival for cases with or without fungal infection was 68% and 87%, respectively
      (P <0.0001). The median intensive care unit stay and overall duration of
      hospitalization were significantly longer for patients with fungal infection (P
      <0.01). The mean time interval from transplantation to the development of fungal
      infection was 15 days (range 4 to 77) with a mean survival time from fungal
      infection to death of 21 days (range 3 to 64). Fungal infections occurred
      significantly more often in patients with renal insufficiency (serum creatinine
      >2.5 mg/dL), biliary/vascular complications, and retransplantation. CONCLUSIONS:
      Fungal infections were associated with increased morbidity and mortality
      following OLTx, with Candida albicans being the most common pathogen. Treatment
      strategies involving antifungal prophylaxis for high-risk patients and earlier
      initiation of antifungal therapy in cases of presumed infection are warranted.

PMID- 10930497
TI  - Exposure to rubber fume and rubber process dust in the general rubber goods, tyre
      manufacturing and retread industries.
AB  - This study assesses the current patterns and levels of exposure to rubber fume
      and rubber process dust in the British rubber industry and compares and contrasts
      the data obtained from the general rubber goods (GRG), retread tire (RT) and new
      tire (NT) sectors. A total of 179 rubber companies were visited and data were
      obtained from 52 general rubber goods, 29 retread tire and 7 new tire
      manufacturers. The survey was conducted using a questionnaire and included a walk
      through inspection of the workplace to assess the extent of use of control
      measures and the nature of work practices being employed. The most recent
      (predominantly 1995-97) exposure monitoring data for rubber fume and rubber
      process dust were obtained from these companies; no additional sampling was
      conducted for the purpose of this study. In addition to the assessment of
      exposure data, evaluation of occupational hygiene reports for the quality of
      information and advice was also carried out.A comparison of the median exposures
      for processes showed that the order of exposure to rubber fume (E, in mg m(-3))
      is: E(moulding) (0.40) approximately E(extrusion) (0.33)>E(milling) (0.18) for
      GRG; E(press) (0. 32)>E(extrusion) (0.19)>E(autoclave) (0.10) for RT; and
      E(press) (0. 22) approximately E(all other) (0.22) for NT. The order of exposure
      to rubber fume between sectors was E(GRG) (0.40)>E(RT) (0.32)>E(NT) (0.22).
      Median exposures to rubber process dust in the GRG was E(weighing)
      (4.2)>>E(mixing) (1.2) approximately E(milling) (0.8) approximately E(extrusion)
      (0.8) and no significant difference (P=0. 31) between GRG and NT sectors. The
      findings compare well with the study carried out in the Netherlands [Kromhout et
      al. (1994), Annals of Occupational Hygiene 38(1), 3-22], and it is suggested that
      the factors governing the significant differences noted between the three sectors
      relate principally to the production and task functions and also to the extent of
      controls employed. Evaluation of occupational hygiene reports indicated a number
      of shortcomings including lack of suitable and sufficient information with regard
      to sampling and analytical methods in use, poor sampling strategy, lack of
      appreciation regarding true rubber process dust, and a poor understanding of the
      principles of control for substances assigned maximum exposure limits.

PMID- 10930498
TI  - Trends in exposure to inhalable particulate and dermal contamination in the
      rubber manufacturing industry: effectiveness of control measures implemented over
      a nine-year period.
AB  - Exposure to inhalable particulates and dermal exposure to cyclohexane soluble
      matter (CSM) were evaluated in seven rubber manufacturing companies in 1988 and
      1997. The identified exposure trends were used to study the effectiveness of
      control measures implemented over a nine-year period. Sampling and analytical
      methodologies were identical in both surveys. Inhalable particulate exposure was
      measured with a PAS6 sampling head. Dermal exposure was assessed by means of a
      dermal pad sampler worn at the lower wrist of the hand of preference. Changes in
      working organization and control measures taken after 1988 were identified based
      on discussions with management representatives and two walk-through surveys
      performed in 1994 and 1997. Exposure data were aggregated for comparison between
      years both at company and production function level. The mixed effect statistical
      procedure was used to evaluate the influence of control measures and seniority on
      current exposure levels. Comparison of the exposure levels between 1988 and 1997
      revealed a reduction rate of 5.7 and 6.7% per year for inhalable particulate and
      dermal exposure, respectively. Companies and production functions with the
      highest exposure levels in 1988 and workers with seniority (more experience)
      showed a steeper decline in exposure levels. Fifty-seven control measures, mostly
      designed to control the levels of inhalable exposure were identified. Elimination
      of sources significantly reduced the inhalable particulate and dermal exposure by
      two-thirds of the level of 1988. Reduction of emission did not show a significant
      overall decrease in exposure concentrations. Control measures designed to control
      the levels of contaminants showed a significant reduction for both inhalable and
      dermal exposure, respectively 34 and 49% of the exposure level of 1988. These
      results indicate that efforts taken to improve work conditions in the rubber
      manufacturing industry in The Netherlands over this decade have been successful
      in reducing both inhalable particulate and dermal contamination.

PMID- 10930499
TI  - Oesophageal cancer and occupational exposure to rubber: a nested case-control
      study.
AB  - Findings for cancer of the oesophagus in the rubber industry are not consistent
      between studies, and derive from too few studies. Few studies were carried out to
      examine risks of oesophageal cancer in different departments and the confounding
      by non-occupational risk factors such as smoking, drinking, and economic status.
      In this paper these questions have been explored. Following a nested case-control
      study, the data were used of nine oesophageal cancer deaths during 1973-1995 and
      36 controls matched for sex and age from the same cohort of a rubber plant
      workers. Oesophageal cancer risks for exposure to rubber were assessed,
      unadjusted and adjusted for non-occupational factors by conditional logistic
      regression. In grouped analysis, odds ratios (ORs) for oesophageal cancer were
      found to be 2.67 (95%CI=0.42,17.0) for milling, etc. workers and 1. 40
      (95%CI=0.24,7.97) for building workers, who worked for one or more years. No
      excess risks were found in the remaining three departments. The models for
      continuous exposure variables indicated that a one-unit year change in the
      milling, etc. department was associated with a 4% increment in the OR. When
      adjusted for serum cholesterol level, the 6% increase (OR) was observed.
      Significant associations between risk for oesophageal cancer and specific
      exposures or processes within the rubber plant were not found. The slight excess
      risk for oesophageal cancer in the rubber plant may be related to exposure to
      dusts and solvents.

PMID- 10930500
TI  - Regression method to estimate provisional TLV/WEEL-equivalents for non
      carcinogens.
AB  - There is a huge and changing number of chemicals in commerce for which workplace
      exposure criteria have not been assigned. Assigning an exposure criterion by an
      expert committee is resource-intensive-not soon available for the large majority
      of chemicals in current use. In the absence of assigned criteria, we have
      provided a regression method to estimate a first-screen estimate of a 'TLV/WEEL
      equivalent' inhalation time-weighted average exposure criterion for a pure
      chemical (or chemical group) from a measure of a non-stochastic toxic exposure to
      elicit a chronic or sub-chronic health effect, known as a lowest observable
      adverse effect level (LOAEL) or a (highest) no observable adverse effect level
      (NOAEL). Results are presented for six data sets for which both a threshold limit
      value (TLV) or workplace environmental exposure level (WEEL) exposure criterion
      is presently assigned, and a LOAEL or NOAEL measure of toxic health effect was
      available from the United States Environmental Protection Agency Integrated Risk
      Information System data base. The results can be applied as a first estimate of
      exposure to substances for which no TLV or WEEL (TLV/WEEL) exists, and also serve
      as a mechanism for identifying substances for potential re-evaluation of their
      exposure limit, based on their relative position about the prediction models.

PMID- 10930501
TI  - Theoretical and numerical predictions of two-dimensional Aaberg slot exhaust
      hoods.
AB  - Theoretical and computational fluid dynamical techniques are employed to predict
      the two-dimensional turbulent air flows which are created by an Aaberg slot
      exhaust hood, which is reinforced by a two-dimensional wall jet flow. The aim of
      the two-dimensional model is to numerically reveal the characteristics of the air
      flow in the central plane of the Aaberg workbench. A further development of the
      potential model is through the inclusion of the finite slot. We have found that
      the numerical results for the streamlines and the lines of constant speed
      produced by the potential flow model are in good agreement with those obtained
      when using the full turbulent flow model and the air velocity distribution
      predicted by both the potential and turbulent models agree very well with all the
      available experimental data. The comparison between the potential and the
      turbulent models reveals that the potential model has the advantage over the
      turbulent model in that there is much less uncertainty in the results obtained
      due to the more accurate specification of the boundary conditions on the open
      boundaries at large distances from the hood.

PMID- 10930502
TI  - Risk of pancreatic cancer and occupational exposures in Spain. PANKRAS II Study
      Group.
AB  - The objective of the study was to analyse the relationship between occupational
      exposures and risk of pancreatic cancer. Incident cases of pancreatic cancer and
      hospital controls were prospectively identified and interviewed during the
      hospital stay. Occupational history was obtained by direct interview with the
      patient, and was available for 164 (89%) of 185 pancreatic cancer cases, and 238
      (90%) of 264 controls. Two industrial hygienists evaluated exposures to 22
      suspected carcinogens previously associated with pancreatic cancer. Occupational
      exposures were also assessed using the Finnish job-exposure matrix (FINJEM). For
      each type of pesticide group, moderately increased odds ratios (OR) were apparent
      in the high-intensity category, highest for arsenical pesticides (OR=3.4; 95% CI
      0.9-12.0), and 'other pesticides' (OR=3.17; 95% CI 1.1-9.2). ORs for aniline
      derivatives, and dyes and organic pigments, were also higher for high-intensity
      exposure, and increased when lagged and restricted to long duration of exposure.
      ORs above 3 were observed for the following agents evaluated by FINJEM:
      pesticides, benzo[a]pyrene, lead, volatile sulphur compounds, and sedentary work.
      Whilst generally negative, results lend moderate support to the hypothesis of an
      association between exposure to some pesticides and pancreatic cancer. Larger
      studies could address the potential for these compounds to modify the
      carcinogenic risk of other environmental exposures. Suggestive increases in risk
      from aniline derivatives, dyes and organic pigments, and benzo[a]pyrene may also
      deserve further attention.

PMID- 10930503
TI  - Primary structure, functional characteristics and tissue expression pattern of
      human ATA2, a subtype of amino acid transport system A.
AB  - We report here on the primary structure and functional characteristics of the
      protein responsible for the system A amino acid transport activity that is known
      to be expressed in most human tissues. This transporter, designated ATA2 for
      amino acid transporter A2, was cloned from the human hepatoma cell line HepG2.
      Human ATA2 (hATA2) consists of 506 amino acids and exhibits a high degree of
      homology to rat ATA2. hATA2-specific mRNA is ubiquitously expressed in human
      tissues. When expressed in mammalian cells, hATA2 mediates Na+-dependent
      transport of alpha-(methylamino)isobutyric acid, a specific model substrate for
      system A. The transporter is specific for neutral amino acids. It is pH-sensitive
      and Li+-intolerant. The Na+:amino acid stoichiometry is 1:1.

PMID- 10930504
TI  - Biochemical evidence for ATPase activity in CFTR-enriched apical membrane
      vesicles from tracheal epithelium.
AB  - In apical membrane vesicles from beef tracheal epithelia expressing up to 30% of
      the proteins as functional cystic fibrosis transmembrane conductance regulator
      (CFTR)-- i.e. a voltage-independent and PKA-sensitive 36Cl- flux--an ATPase
      activity, different from P, F0F1 and V types, was reproducibly detected. Its
      specific activity averaged 20 micromol Pi h(-1) mg(-1) with an apparent affinity
      for ATP of 530 +/- 30 microM. Its possible involvement in CFTR functions was
      supported by (1) the linear relationship between the ATPase activity and the
      magnitude of 36Cl- fluxes (turnover rate: 3 ATP hydrolyzed per CFTR per second),
      (2) the same rank of potency of ATP, ITP, GTP, UTP and CTP to be hydrolyzed and
      to open CFTR chloride channels, (3) the similar and parallel inhibition of the
      ATPase and CFTR Cl- fluxes by NS004 (IC50: 60 microM) and (4) the potency of anti
      R domain antibodies to increase by 18% the ATPase activity.

PMID- 10930505
TI  - Formation and characterization of
      phosphatidylethanolamine/lysophosphatidylcholine mixed vesicles.
AB  - The lipid aggregates formed by adding lysophosphatidylcholine (lysoPC) solution
      to phosphatidylethanolamine (PE) dispersion at 4 degrees C followed by incubating
      it at 37 degrees C were proved to be a vesicle system judged from the negatively
      stained electron micrographs and the latency of calcein fluorescence. The results
      obtained are analogous to those described for phosphatidylcholine (PC) vesicles.
      The chromatography results showed that the incorporation of PE and lysoPC into
      the PE/lysoPC vesicles was in a molar ratio of 5 to 2. The PE/lysoPC membrane was
      found to have similar barrier potentials for Cl- or calcein efflux to the PC
      membrane. 1H Nuclear magnetic resonance measurement suggested that lysoPC
      dominated the external monolayer of the vesicles. Furthermore, it was found that
      PE/lysoPC vesicles and micelles could coexist when a large amount of lysoPC was
      added to the PE/lysoPC vesicle suspension. The formation of PE/lysoPC vesicles is
      discussed in combination with the inhibition of interlayer attachment by lysoPC
      from the PE membrane.

PMID- 10930506
TI  - Electrochemical and NMR spectroscopic investigations of the influence of the
      probe molecule Eu(fod)3 on the permeability of lipid membranes to ions.
AB  - Investigating the action of the fluorinated europium complex Eu(fod)3 on lipid
      membranes we found that the complex facilitates the ion transfer through the
      membrane. Electric measurements on planar lipid membranes showed that the
      membrane conductivity increases considerably by insertion of the complex into the
      membrane. The increase in the conductivity was only obtained if both layers of
      the membrane were modified with the complex. 1H NMR spectroscopic studies using
      DOPC liposomes gave information about the location of the modifier complex in the
      lipid membrane. From chemical shift effects we concluded that the complex resides
      in the choline head group region of the membrane and also in the membrane
      interior near the -C =C- lipid double bond, but not in the center of the bilayer.
      For understanding of the mentioned conductivity effect we assume that the
      europium complex induces defects of yet unknown structure in the lipid matrix
      which provide paths for the ion transfer through the membrane. As appropriate
      measurements revealed, these paths seem to conduct cations predominantly.
      Investigating the current voltage behavior of the modified lipid membranes in
      dependence on the ion concentration we obtained different shaped current-voltage
      curves. Calculation showed that a model with only one energy barrier inside the
      membrane is unable to describe these curves kinetically. However, by assuming two
      energy barriers--one barrier in each membrane lipid layer--the observed curve can
      be described satisfactorily.

PMID- 10930507
TI  - Interactions between cholesterol and lipids in bilayer membranes. Role of lipid
      headgroup and hydrocarbon chain-backbone linkage.
AB  - We have employed four lipids in the present study, of which two are cationic and
      two bear phosphatidylcholine (PC) headgroups. Unlike
      dipalmitoylphosphatidylcholine, the other lipids employed herein do not have any
      ester linkage between the hydrocarbon chains and the respective lipid backbones.
      Small unilamellar vesicles formed from each of the PC and cationic lipids with or
      without varying amounts of cholesterol have been examined using the steady-state
      fluorescence anisotropy method as a function of temperature. The anisotropy data
      clearly indicate that the order in the lipid bilayer packing is strongly affected
      upon inclusion of cholesterol. This effect is similar irrespective of the
      electrostatic character of the lipid employed. The influence of cholesterol
      inclusion on multi-lamellar lipid dispersions has also been examined by 1H
      nuclear magnetic resonance spectroscopy above the phase transition temperatures.
      With all the lipids, the line widths of (CH2)n protons of hydrocarbon chains in
      the NMR spectra respond to the addition of cholesterol to membranes. The
      influence on the bilayer widths of various lipids upon inclusion of cholesterol
      was determined from X-ray diffraction studies of the cast films of the lipid
      cholesterol coaggregates in water. The effect of cholesterol on the efflux rates
      of entrapped carboxyfluorescein (CF) from the phospholipid vesicles was
      determined. Upon incremental incorporation of cholesterol into the phospholipid
      vesicles, the CF leakage rates were progressively reduced. Independent
      experiments measuring transmembrane OH- ion permeation rates from cholesterol
      doped cationic lipid vesicles using entrapped dye riboflavin also demonstrated
      that the addition of cholesterol into the cationic lipid vesicles reduced the
      leakage rates irrespective of lipid molecular structure. It was found that the
      cholesterol induced changes on the membrane properties such as lipid order,
      linewidth broadening, efflux rates, bilayer widths, etc., did not depend on the
      ability of the lipids to participate in the hydrogen bonding interactions with
      the 3beta-OH of cholesterol. These findings emphasize the importance of
      hydrophobic interaction between lipid and cholesterol and demonstrate that it is
      not necessary to explain the observed cholesterol induced effects on the basis of
      the presence of hydrogen bonding between the 3beta-OH of cholesterol and the
      lipid chain-backbone linkage region or headgroup region.

PMID- 10930508
TI  - Wortmannin inhibition of forskolin-stimulated chloride secretion by T84 cells.
AB  - The time- and dose-dependent effects of wortmannin on transepithelial electrical
      resistance (Rte) and forskolin-stimulated chloride secretion in T84 monolayer
      cultures were studied. In both instances, maximal effects developed over 2 h and
      were stable thereafter. Inhibition of forskolin-stimulated chloride secretion, as
      measured by the short-circuit current (Isc) technique, had an IC50 of 200-500 nM,
      which is 100-fold higher than for inhibition of phosphatidylinositol 3-kinase
      (PI3K), but similar to the IC50 for inhibition of myosin light chain kinase
      (MLCK) and mitogen-activated protein kinases (MAPK). Previous work demonstrated
      that 500 nM wortmannin did not inhibit the cAMP activation of apical membrane
      chloride channels. We show here that 500 nM wortmannin has no affect on
      basolateral Na/K/2Cl-cotransporter activity, but inhibits basolateral membrane
      Na/K-ATPase activity significantly. The MLCK inhibitors ML-7 and KT5926 were
      without affect on forskolin-stimulated Isc. Similarly, the p38- and MEK-specific
      MAPK inhibitors SB203580 and PD98059 did not reduce forskolin-stimulated Isc. In
      contrast, the non-specific MAPK inhibitor apigenin reduced forskolin-stimulated
      Isc and basolateral membrane Na/K-ATPase activity similar to wortmannin. In
      isolated membranes from T84 cells, wortmannin did not inhibit Na/K-ATPase
      enzymatic activity directly. We conclude that one or more MAPK may regulate the
      functional expression of basolateral membrane Na/K-ATPase by controlling the
      abundance of enzyme molecules in the plasma membrane.

PMID- 10930509
TI  - Steady-state tyrosine fluorescence to study the lipid-binding properties of a
      wheat non-specific lipid-transfer protein (nsLTP1).
AB  - The binding properties of a wheat non-specific lipid-transfer protein (nsLTP1)
      for different mono- and diacylated lipids was investigated. Lipids varied by
      their chain length, unsaturation and/or polar head group. In the case of fatty
      acid or lysophospholipid with a C10 chain length, no interaction can be measured,
      while poor affinity is reported for a C12 chain length. The dissociation constant
      (Kd) is about 0.5 microM independent of chain length from C14 to C18. The same
      affinity is obtained for C18 fatty acids with one or two unsaturations, whatever
      the cis-trans double bond isomery. In all cases, the number of binding sites, n,
      by protein ranges between 1.6 and 1.9, suggesting that two lipids can fit within
      the protein. omega-Hydroxy-palmitic acid, a natural monomer of cutin polymer, is
      found to interact with nsLTP1 with a Kd of 1 microM and n = 2. In contrast with
      previous data that reported the binding of the anionic diacylated phospholipid,
      DMPG (Sodano et al., FEBS Lett. 416 (1997) 130-134), nsLTP1 is not able to bind
      dimyristoylphosphatidylcholine, dimyristoylphosphatidic acid, palmitoyl
      oleoylphosphatidylcholine or palmitoyl-oleoylphosphatidylglycerol added as
      liposomes or solubilized in ethanol. However, when both nsLTP1 and lipids are
      first solubilized in methanol, and then in the buffer, it was evidenced that the
      protein can bind these lipids. These results suggest that lipid-lipid
      interactions play an essential role in the binding process of plant nsLTP1 as
      previously mentioned for other lipid-transfer proteins.

PMID- 10930510
TI  - Requirement of the hinge domain for dimerization of Ca2+-ATPase large cytoplasmic
      portion expressed in bacteria.
AB  - The large cytoplasmic domain of rabbit sarcoplasmic reticulum Ca2+-ATPase was
      overexpressed in Escherichia coli as a 48 kDa fusion protein, designated p48,
      containing an N-terminal hexa-His tag. Purification conditions were optimized,
      thus conferring long-term stability to p48. Circular dichroism spectroscopy and
      the pattern of limited trypsinolysis confirmed the proper folding of the domain.
      p48 retained 0.5 +/- 0.1 mol of high affinity 2',3'-O-(2,4,6
      trinitrophenyl)adenosine-5'-triphosphate (TNP-ATP) binding sites per mol of
      polypeptide chain with an apparent dissociation constant of about 8 microM. Size
      exclusion FPLC using protein concentrations in the range 0.03 5 mg/ml showed that
      p48 was essentially monodisperse with apparent molecular mass and Stokes radius
      (Rs) values compatible with a dimer (100 kDa and 40 A, respectively). Analysis of
      p48 by small-angle X-ray scattering provided an independent second proof for a
      dimeric p48 particle with a radius of gyration (Rg) of 39 A, suggesting that the
      dimer was not spherical (Rs/Rg = 1.026). When digested by proteinase K, p48 was
      converted to a 30 kDa fragment, designated p30, which was very resistant to
      further proteolysis. p30 retained high affinity TNP-ATP binding (Kd = 8 microM)
      and eluted as a monomer (35 kDa) in size-exclusion FPLC. As opposed to p48, the
      p30 fragment did not react with monoclonal antibody A52 [Clarke et al., J. Biol.
      Chem. 264 (1989) 11246-11251] which recognizes region E657-R672 located upstream
      of the hinge domain of the Ca2+-ATPase. These results indicate a requirement of
      the hinge domain (670-728) region for self-association of the p48 large
      hydrophilic domain as a dimer. We propose that this behavior points to a possible
      role of the hinge domain in dimerization of sarcoplasmic reticulum Ca2+-ATPase in
      the native membrane.

PMID- 10930511
TI  - Plasma membrane coating with cationic silica particles and osmotic shock alters
      the morphology of bovine aortic endothelial cells.
AB  - We have used a published method of membrane preparation based on the precoating
      of the apical membrane of aortic endothelial cells with cationic silica
      microbeads (with or without polyacrylic acid) in combination with an osmotic
      shock and mechanical shearing to isolate the apical from the basal plasma
      membranes of these cells, in vitro. After labeling of the plasma membrane of
      adherent endothelial cells with a fluorescent derivative of phosphatidylcholine
      and by using laser confocal fluorescence scanning microscopy, we found that this
      method of membrane isolation rapidly induced invaginations of the basal plasma
      membrane to an extent which makes this method unsuitable for further membrane
      lipid analysis. Morphological analysis of the cells and fluorescence recovery
      after photobleaching experiments on the plasma membranes were performed at each
      step of the purification procedure and showed that only hypotonic shock and
      mechanical shearing of the cells enabled the basal plasma membranes to be
      purified without significant morphological changes.

PMID- 10930513
TI  - Partition of membrane probes in a gel/fluid two-component lipid system: a
      fluorescence resonance energy transfer study.
AB  - A non-ideal lipid binary mixture
      (dilauroylphosphatidylcholine/distearoylphosphatidylcholine), which exhibits
      gel/fluid phase coexistence for wide temperature and composition ranges, was
      studied using photophysical techniques, namely fluorescence anisotropy, lifetime
      and resonance energy transfer (FRET) measurements. The FRET donor, N-(7-nitrobenz
      2-oxa-1,3-diazol-4-yl)-dilauroylphosphatidylethanol amine, and a short-tailed
      FRET acceptor, 1,1'-didodecil-3,3,3',3'-tetramethylindocarbocyanine (DiIC12(3)),
      were shown to prefer the fluid phase by both intrinsic anisotropy, lifetime and
      FRET measurements, in agreement with published reports. The other studied FRET
      acceptor, long-tailed probe 1,1'-dioctadecil-3,3,3',3'
      tetramethylindocarbocyanine (DiIC18(3)), is usually reported in the literature as
      partitioning mainly to the gel. While intrinsic lifetime studies indeed indicated
      preferential partition of DiIC18(3) into a rigidified environment, FRET analysis
      pointed to an increased donor-acceptor proximity as a consequence of phase
      separation. These apparently conflicting results were rationalized on the basis
      of segregation of DiIC18(3) to the gel/fluid interphase. In order to fluid
      located donors sense these interphase-located acceptors, fluid domains should be
      small (not exceed approximately 10-15 nm). It is concluded that membrane probes
      which apparently prefer the gel phase may indeed show a non-random distribution
      in this medium, and tend to locate in an environment which simultaneously leads
      to less strict packing constraints and to favorable hydrophobic matching
      interactions.

PMID- 10930512
TI  - Swelling-induced taurine release without chloride channel activity in Xenopus
      laevis oocytes expressing anion channels and transporters.
AB  - Taurine is an important osmolyte involved in cell volume regulation. During
      regulatory volume decrease it is released via a volume-sensitive organic
      osmolyte/anion channel. Several molecules have been suggested as candidates for
      osmolyte release. In this study, we chose three of these, namely ClC-2, ClC-3 and
      ICln, because of their expression in rat astrocytes, a cell type which is known
      to release taurine under hypotonic stress, and their activation by hypotonic
      shock. As all three candidates were also suggested to be chloride channels, we
      investigated their permeability for both chloride and taurine under isotonic and
      hypotonic conditions using the Xenopus laevis oocyte expression system. We found
      a volume-sensitive increase of chloride permeability in ClC-2-expressing oocytes
      only. Yet, the taurine permeability was significantly increased under hypotonic
      conditions in oocytes expressing any of the tested candidates. Further
      experiments confirmed that the detected taurine efflux does not represent
      unspecific leakage. These results suggest that ClC-2, ClC-3 and ICln either
      participate in taurine transport themselves or upregulate an endogenous oocyte
      osmolyte channel. In either case, the taurine efflux of oocytes not being
      accompanied by an increased chloride flux suggests that taurine and chloride can
      be released via two separate pathways.

PMID- 10930514
TI  - Influence of the glycopeptidic moiety of mycobacterial glycopeptidolipids on
      their lateral organization in phospholipid monolayers.
AB  - Glycopeptidolipids (GPLs) from the cell wall of opportunistic pathogenic
      mycobacteria are potential factors of pathogenicity which can interact with
      biological membranes. GPL suspensions uncouple oxidative phosphorylation of
      mitochondria and increase membrane permeability of liposomes. Heavily
      glycosylated GPLs are less active than lightly glycosylated ones. GPL
      phospholipid interactions into preformed mixed films at the air-water interface
      were investigated in order to understand the permeabilization efficiency
      differences among GPLs. Polarization modulation infrared reflection absorption
      spectroscopy (PMIRRAS) was used to determine, in situ, the organization of GPL
      and of 1,2-di(perdeuteropalmitoyl)phosphatidylcholine (DPPC) molecules in mixed
      films. Compression isotherms of GPL alone or mixed with DPPC in various
      proportions showed that the less the GPL was glycosylated the higher its
      miscibility with DPPC. PMIRRAS studies indicated that low miscibility may result
      from large self-association of GPL molecules in beta-sheet structures. Low
      glycosylated GPL molecules increased disorder of DPPC acyl chains. Based on these
      results, an explanatory model is proposed for membrane permeabilization. Increase
      of passive permeability may arise from disruption of phospholipid packing induced
      by GPL molecules. GPL segregation is proposed as the cause of low activity of GPL
      with high sugar content, by decreasing the number of GPL molecules interacting
      with phospholipids.

PMID- 10930515
TI  - Oriented circular dichroism of a class A amphipathic helix in aligned
      phospholipid multilayers.
AB  - The effect of lipid phase state on the orientation and conformation of a class A
      alpha-helical peptide on aligned lipid multilayers was examined using oriented
      circular dichroism spectroscopy. A comparison of oriented spectra in aligned
      peptide-lipid multilayers with CD spectra of unaligned peptide lipid vesicle
      complexes is consistent with a preferential alignment of helices parallel to the
      membrane surface at temperatures above and below the main acyl-chain melting
      transition temperature of the phospholipid. Changes are observed in the oriented
      CD spectra with lipid phase state which are attributed to a subtle conformational
      change of the peptide on the lipid surface. The results are compared with
      available experimental data on membrane-active lytic and antimicrobial helical
      peptides.

PMID- 10930516
TI  - Interaction of the third helix of Antennapedia homeodomain and a phospholipid
      monolayer, studied by ellipsometry and PM-IRRAS at the air-water interface.
AB  - The penetratin peptide, a 16 amino acid sequence extracted from Antennapedia
      homeodomain, is able to translocate across a neural cell membrane through an
      unknown mechanism, most likely a non-specific interaction with membrane lipids.
      Beyond its potential application as vector targeting small hydrophilic molecules
      and enabling them to reach a cell nucleus, this observation raises intriguing
      questions concerning the physico-chemistry of peptide-lipid interactions. Here we
      present a study of the role of lipid surface pressure and head charge on the
      mechanism of interaction. This was performed using optical techniques: surface
      infrared spectroscopy and ellipsometry, applied to a monolayer of phospholipids
      deposited at the air-water interface. Determination of the structure and
      orientation of peptides and lipids (separately or together) evidenced that
      electrostatic rather than amphiphilic interactions determine the peptide
      adsorption and its action on lipids.

PMID- 10930517
TI  - Glycosylphosphatidylinositol-anchored proteins are not required for crosslinking
      mediated endocytosis or transfection of avidin bioconjugates into biotinylated
      cells.
AB  - Even though glycosylphosphatidylinositol (GPI)-anchored proteins lack direct
      structural contact with the intracellular space, these ubiquitously expressed
      surface receptors activate signaling cascades and endocytosis when crosslinked by
      extracellular ligands. Such properties may be due to their association with
      membrane microdomains composed of glycosphingolipids, cholesterol and some
      signaling proteins. In this study, we hypothesize that GPI proteins may be
      required for crosslinking-mediated endocytosis of extracellular bioconjugates. To
      test this hypothesis, we first biotinylated the surface membranes of native K562
      erythroleukemia cells versus K562 cells incapable of surface GPI protein
      expression. We then compared the entry of fluorescently labeled avidin or DNA
      condensed on polyethylenimine-avidin bioconjugates into the two biotinylated cell
      populations. Using fluorescence microscopy, nearly 100% efficiency of fluorescent
      avidin endocytosis was demonstrated in both cell types over a 24 h period.
      Surprisingly, plasmid DNA transfer was slightly more efficient among the
      biotinylated GPI-negative cells as measured by the expression of green
      fluorescence protein. Our findings that GPI proteins are not required for the
      endocytosis of avidin bioconjugates into biotinylated cells suggest that
      endocytosis associated with general membrane crosslinking may be due to overall
      reorganization of the membrane domains rather than GPI protein-specific
      interactions.

PMID- 10930518
TI  - Interactions of the HIV-1 fusion peptide with large unilamellar vesicles and
      monolayers. A cryo-TEM and spectroscopic study.
AB  - We have examined the interaction of the human immunodeficiency virustype 1 fusion
      peptide (23 amino acid residues) and of a Trp-containing analog with vesicles
      composed of dioleoylphosphatidylcholine, dioleoylphosphatidylethanolamine and
      cholesterol (molar ratio, 1:1:1). Both the native and the Trp-substituted
      peptides bound the vesicles to the same extent and induced intervesicular lipid
      mixing with comparable efficiency. Infrared reflection-absorption spectroscopy
      data are compatible with the adoption by the peptide of a main beta-sheet
      structure in a cospread lipid/peptide monolayer. Cryo-transmission electron
      microscopy observations of peptide-treated vesicles reveal the existence of a
      peculiar morphology consisting of membrane tubular elongations protruding from
      single vesicles. Tryptophan fluorescence quenching by brominated phospholipids
      and by water-soluble acrylamide further indicated that the peptide penetrated
      into the acyl chain region closer to the interface rather than into the bilayer
      core. We conclude that the differential partition and shallow penetration of the
      fusion peptide into the outer monolayer of a surface-constrained bilayer may
      account for the detected morphological effects. Such single monolayer-restricted
      interaction and its structural consequences are compatible with specific
      predictions of current theories on viral fusion.

PMID- 10930519
TI  - Deletion analogues of transportan.
AB  - Several shorter analogues of the cell penetrating peptide, transportan, have been
      synthesized in order to define the regions of the sequence, which are responsible
      for the membrane translocation property of the peptide. Penetration of the
      peptides into Bowes melanoma cells and the influence on GTPase activity in Rin
      m5F cellular membranes have been tested. The experimental data on cell
      penetration have been compared with molecular modeling of insertion of peptides
      into biological membranes. Omission of six amino acids from the N-terminus did
      not significantly impair the cell penetration of the peptide while deletions at
      the C-terminus or in the middle of the transportan sequence decreased or
      abolished the cellular uptake. Most transportan analogues exert an inhibitory
      effect on GTPase activity. Molecular modeling shows that insertion of the
      transportan analogues into the membrane differs for different peptides. Probably
      the length of the peptide as well as the location of aromatic and positively
      charged residues have major impact on the orientation of peptides in the
      membranes and thereby influence the cellular penetration. In summary, we have
      designed and characterized several novel short transportan analogues with similar
      cellular translocation properties to the parent peptide, but with reduced
      undesired cellular activity.

PMID- 10930520
TI  - Giant vesicles as models to study the interactions between membranes and
      proteins.
AB  - The interaction between polypeptides and membranes is a fundamental aspect of
      cell biochemistry. Liposomes have been used in this context as in vitro systems
      to study such interactions. We present here the case of giant vesicles (GVs),
      which, due to their size (radius larger than 10 microns), mimic more closely the
      situation observed in cell membranes and furthermore permit to study protein
      membrane interactions by direct optical monitoring. It is shown that GVs formed
      from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine by electroformation are
      permeable to certain low molecular weight molecules such as the nucleic acid dye
      YO-PRO-1 and fluorescein diphosphate whereas conventional liposomes (large or
      small unilamellar liposomes) are not. In addition, it is shown that non-membrane
      proteins, such as DNases or RNases, added to the selected GVs from the outside,
      are able to convert their substrate, which is strictly localized on the internal
      side of the membrane. This effect is only seen in GVs (also when they are removed
      from the original electroformation environment) and is absent in conventional
      liposomes. The fact that these effects are only present in GVs obtained by
      electroformation and not in conventional small liposomes is taken as an
      indication that certain physico-chemical properties of the bilayer are affected
      by the membrane curvature, although the mechanism underlying such differences
      could not be established as yet.

PMID- 10930521
TI  - Angiotensin-(1-7) modulates the ouabain-insensitive Na+-ATPase activity from
      basolateral membrane of the proximal tubule.
AB  - Angiotensin-(1-7) (Ang-(1-7)) modulates the Na+-ATPase, but not the Na+,K+-ATPase
      activity present in pig kidney proximal tubules. The Na+-ATPase, insensitive to
      ouabain, but sensitive to furosemide, is stimulated by Ang-(1-7) (68% by 10(-9)
      M), in a dose-dependent manner. This effect is due to an increase in Vmax, while
      the apparent affinity of the enzyme for Na+ is not modified. Saralasin, a general
      angiotensin receptor antagonist, abolishes the stimulation, demonstrating that
      the Ang-(1-7) effect is mediated by receptor. The Ang-(1-7) stimulatory effect is
      not changed by either PD 123319, an AT2 receptor antagonist, or A779, an Ang-(1
      7) receptor antagonist. On the other hand, increasing the concentration of the
      AT1 receptor antagonist losartan from 10(-11) to 10(-9) M, reverses the Ang(1-7)
      stimulation completely. A further increase to 10(-3) M losartan reverses the Na+
      ATPase activity to a level similar to that obtained with Ang-(1-7) (10(-9) M)
      alone. The stimulatory effect of Ang-(1-7) at 10(-9) M is similar to the effect
      of angiotensin II (AG II) alone. However, when the two peptides are both present,
      Na+-ATPase activity is restored to control values. These data suggest that Ang-(1
      7) selectively modulates the Na+-ATPase activity present in basolateral membranes
      of kidney proximal tubules through a losartan-sensitive receptor. This receptor
      is probably different from the receptor involved in the stimulation of the Na+
      ATPase activity by angiotensin II.

PMID- 10930522
TI  - Order-disorder transition in bilayers of diphytanoyl phosphatidylcholine.
AB  - A comparative study on bilayers of diphytanoyl phosphatidylcholine (DPhPC) and
      bilayers of dimyristoyl phosphatidylcholine (DMPC) was made by X-ray lamellar
      diffraction as a function of temperature and the degree of hydration. An order
      disorder phase transition of DPhPC reveals an interesting contrast to the
      standard model of DMPC. Electron density profiles allow us to deduce the
      conformational changes which occur in the headgroup-glycerol region and in the
      chain region. The important conclusion is that the lipid headgroup may have
      different conformational energetics in lipids of different chains. We explain why
      this is important to protein-membrane interactions.

PMID- 10930523
TI  - The yeast mitochondrial transport proteins: new sequences and consensus residues,
      lack of direct relation between consensus residues and transmembrane helices,
      expression patterns of the transport protein genes, and protein-protein
      interactions with other proteins.
AB  - Mitochondrial transport proteins (MTP) typically are homodimeric with a 30-kDa
      subunit with six transmembrane helices. The subunit possesses a sequence motif
      highly similar to Pro X Asp/Glu X X Lys/Arg X Arg within each of its three
      similar 10-kDa segments. Four (YNL083W, YFR045W, YPR021C, YDR470C) of the 35
      yeast (S. cerevisiae) MTP genes were resequenced since the masses of their
      proteins deviate significantly from the typical 30 kDa. We now find these four
      proteins to have 545, 285, 902, and 502 residues, respectively. Together with
      only four other MTPs, the sequences of YPR021C and YDR470C show substitutions of
      some of the five residues that are absolutely conserved among the 12 MTPs with
      identified transport function and 17 other MTPs. We do now find these five
      consensus residues also in the new sequences of YNL083W and YFR045W. Additional
      analyses of the 35 yeast MTPs show that the location of transmembrane helix
      sequences do not correlate with the general consensus residues of the MTP family;
      protein segments connecting the six transmembrane helices and facing the
      intermembrane space are not uniformly short (about 20 residues) or long (about 40
      residues) when facing the matrix; most MTPs have at least one transmembrane helix
      for which the sum of the negative hydropathy values of all residues yields a very
      small negative value, suggesting a membrane location bordering polar faces of
      other transmembrane helices or a non-transmembrane location. The extra residues
      of the three large MTPs are hydrophilic and at the N-terminal. The 200-residue N
      terminal segment of YNL083W has four putative Ca2+-binding sites. The 500-residue
      N-terminal segment of YPR021C shows sequence similarity to enzymes of nucleic
      acid metabolism. cDNA microarray data show that YNL083W is expressed solely
      during sporulation, while the expressions of YFR045W, YPR021C, and YDR470C are
      induced by various stress situations. These results also show that the 35 MTP
      genes are expressed under a rather diverse set of metabolic conditions that may
      help identify the function of the proteins. Interestingly, yeast two-hybrid
      screens, that will also be useful in identifying the function of MTPs, indicate
      that MIR1, AAC3, YOR100C, and YPR011C do interact with non-MTPs.

PMID- 10930524
TI  - Optical characterization of liposomes by right angle light scattering and
      turbidity measurement.
AB  - Liposomes have frequently been used as models of biomembranes or vehicles for
      drug delivery. However, the systematic characterization of lipid vesicles by
      right angle light scattering and turbidity has not been carried out despite the
      usefulness of such studies for size estimation. In this study, liposomes of
      various sizes were prepared by sonication and extrusion. The mean cumulant radii
      of the vesicles were determined by dynamic light scattering. The lamellarities
      were estimated based on fluorescence quenching of N-(7-nitrobenz-2-oxa-1,3-diazol
      4-yl)dipalmitoyl-L-alpha-phosph ati dylethanolamine by sodium dithionite. Right
      angle light scattering intensity and optical density at 436 nm per unit lipid
      concentration were measured as a function of vesicle radius. With a vesicle
      radius < or =100 nm, the optical parameters could be well explained by the
      Rayleigh-Gans-Debye theory in which the liposomes were modeled as homogeneous
      spheres with mean refractive indices determined by the volume fractions of lipids
      in vesicles.

PMID- 10930525
TI  - Novel inner monolayer fusion assays reveal differential monolayer mixing
      associated with cation-dependent membrane fusion.
AB  - The ability to specifically monitor the behavior of the inner monolayer lipids of
      membranous vesicles during the membrane fusion process is useful technically and
      experimentally. In this study, we have identified N-NBD-phosphatidylserine as a
      reducible probe particularly suitable for inner monolayer fusion assays because
      of its low rate of membrane translocation after reduction of the outer monolayer
      probes by dithionite. Data are presented on translocation as a function of
      temperature, vesicle size, membrane composition, and serum protein concentration.
      Translocation as a result of the fusion event itself was also characterized. We
      further show here that a second membrane-localized probe, a long wavelength
      carbocyanine dye referred to a diI(5)C18ds, appears to form a membrane-bound
      resonance energy transfer pair with N-NBD-PS, and its outer monolayer
      fluorescence can also be eliminated by dithionite treatment. Lipid dilution of
      these probes upon fusion with unlabeled membranes leads to an increase in NBD
      donor fluorescence, and hence is a new type of inner monolayer fusion assay.
      These inner monolayer probe mixing assays were compared to random lipid labeling
      and aqueous contents mixing assays for cation-dependent fusion of liposomes
      composed of phosphatidylserine and phosphatidylethanolamine. The results showed
      that the inner monolayer fusion assay eliminates certain artifacts and reflects
      fairly closely the rate of non-leaky mixing of aqueous contents due to fusion,
      while outer monolayer mixing always precedes mixing of aqueous contents. In fact,
      vesicle aggregation and outer monolayer lipid mixing were found to occur over
      very long periods of time without inner monolayer mixing at low cation
      concentrations. Externally added lysophosphatidylcholine inhibited vesicle
      aggregation, outer monolayer mixing and any subsequent fusion. The state of
      vesicle aggregation and outer monolayer exchange that occurs below the fusion
      threshold may represent a metastable intermediate state that may be useful for
      further studies of the mechanism of membrane fusion.

PMID- 10930526
TI  - Identification of three new members of the phospholipid scramblase gene family.
AB  - Phospholipid (PL) scramblase is a 35 kDa protein that is thought to mediate Ca2+
      induced bidirectional transbilayer movement of plasma membrane phospholipids in
      activated, injured, or apoptotic cells. We recently reported the molecular
      cloning of a PL scramblase of human (HuPLSCR1) and mouse origin, respectively. In
      the present study, the gene for HuPLSCR1 was cloned from a human genomic library.
      The gene size is 29.7 kb and includes nine exons. Analysis of the 5' flanking
      genomic sequence with luciferase reporter constructs located the promoter to a
      region spanning from -95 to +60 of the first (untranslated) exon. Furthermore, we
      report the molecular cloning of three additional novel cDNAs encoding proteins
      with high homology to HuPLSCR1. The predicted open reading frames encode proteins
      with 59% (HuPLSCR2; 224 aa), 47% (HuPLSCR3; 295 aa) and 46% (HuPLSCR4; 329 aa)
      identity, respectively, to HuPLSCR1. All members of the PLSCR gene family
      conserve those residues contained in the segment of the PLSCR1 polypeptide that
      was previously shown to bind Ca2+. With the exception of HuPLSCR2, these proteins
      also each contain multiple PXXP motifs and a PPXY motif located near the N
      terminus, implying the potential for interaction with SH3 or WW domain-containing
      proteins, respectively. HuPLSCR1, 2, and 4 were found to be closely clustered on
      chromosome 3 (3q23), whereas HuPLSCR3 is located on chromosome 17. Northern blots
      revealed that the expression of HuPLSCR2 is restricted to testis, whereas
      HuPLSCR1, 3 and 4 are expressed in most of the 16 tissues examined. Notable
      exceptions were HuPLSCR4, which was not detected in peripheral blood lymphocytes,
      and HuPLSCR1 and HuPLSCR3, which were not detected in brain.

PMID- 10930527
TI  - K(ATP) channels: linker between phospholipid metabolism and excitability.
AB  - ATP-sensitive potassium (K(ATP)) channels couple electrical activity to cellular
      metabolism via their inhibition by intracellular ATP. When examined in excised
      patches, ATP concentrations required for half-maximal inhibition (IC(50)) varied
      among tissues and were reported to be as low as 10 microM. This set up a puzzling
      question on how activation of K(ATP) channels can occur under physiological
      conditions, where the cytoplasmic concentration of ATP is much higher than that
      required for channel inhibition. A new twist was added to this puzzle when two
      recent reports showed that phospholipids such as phosphatidylinositol-4,5
      bisphosphate (PIP(2)) and phosphatidyl-4-phosphate (PIP) are able to shift ATP
      sensitivity of K(ATP) channels from the micro- into the millimolar range and thus
      provide a mechanism for physiological activation of the channels. This commentary
      describes how phospholipids control ATP inhibition of K(ATP) channels and how
      this mechanism is regulated effectively by receptor-mediated stimulation of
      phospholipase C.

PMID- 10930528
TI  - Down-regulation of Na(+)/K(+)-ATPase alpha(2) isoform in denervated rat vas
      deferens.
AB  - In the rat vas deferens, an organ richly innervated by peripheral sympathetic
      neurons, we have demonstrated recently the expression of alpha(1) and alpha(2),
      but not alpha(3) isoforms of the alpha subunit of Na(+)/K(+)-ATPase (EC
      3.6.1.37), a membrane-bound enzyme of vital function for living cells (Noel et
      al., Biochem Pharmacol 55: 1531-1535, 1998). In the present work, we
      characterized, qualitatively and quantitatively, Na(+)/K(+)-ATPase alpha isoforms
      in denervated rat vasa deferentia. [(3)H]Ouabain binding at concentrations
      defined for high-affinity isoforms (alpha(2) and/or alpha(3)) detected only one
      class of specific binding sites in control (C) and denervated (D) vas deferens.
      Although the dissociation constant was similar for both groups [K(d) = 138 +/- 14
      nM (C) and 125 +/- 8 nM (D)], a marked decrease in density was observed after
      denervation [716 +/- 81 fmol.mg protein(-1) (C) and 445 +/- 34 fmol.mg protein(
      1) (D), P < 0.05]. In addition, western blotting revealed that denervated vasa
      deferentia produce the alpha(1) and alpha(2) isoforms but not alpha(3), just as
      we reported for the controls previously (Noel et al., Biochem Pharmacol 55: 1531
      1535, 1998). Densitometric analysis showed a decrease of the alpha(2) isoform by
      about 40% in denervated organs, in very good agreement with what was shown with
      the [(3)H]ouabain binding technique, but no significant change in alpha(1)
      isoform density. Truncated alpha(1) (alpha(1)T), an isoform suggested to exist in
      the guinea pig vas deferens, was not detected. Altogether, our results
      demonstrated that Na(+)/K(+)-ATPase alpha(2) is down-regulated after sympathetic
      denervation of the rat vas deferens.

PMID- 10930529
TI  - Induction of oxidative stress and apoptosis in myeloma cells by the aziridine
      containing agent imexon.
AB  - Imexon is an iminopyrrolidone derivative that has selective antitumor activity in
      multiple myeloma. The exact mechanism of imexon action is unknown. In human 8226
      myeloma cells, the cytotoxicity of imexon was schedule-dependent, and long
      exposures (> or = 48 hr) to low concentrations of imexon were most effective at
      inducing cytotoxicity. Our data suggest that imexon does not affect DNA, but it
      can alkylate thiols by binding to the sulfhydryl group. We have also demonstrated
      by HPLC studies that in human 8226 myeloma cells, imexon depletes cellular stores
      of cysteine and glutathione. Oxidative stress in 8226 cells exposed to imexon was
      detected by immunohistochemical staining with a monoclonal antibody to 8
      hydroxydeoxyguanosine (8-OHdG), followed by confocal microscopy. These images
      showed increased levels of 8-OHdG in the cytoplasm of cells treated with
      different concentrations of imexon at 8, 16, and 48 hr. Interestingly, 8-OHdG
      staining was not observed in the nuclei of imexon-treated cells, in contrast to
      the diffuse staining seen with t-butyl hydroperoxide. Myeloma cells exposed to
      imexon showed classic morphologic features of apoptosis upon electron microscopy,
      and increased levels of phosphatidylserine exposure, detected as Annexin-V
      binding, on the cell surface. To prevent depletion of thiols, 8226 myeloma cells
      exposed to imexon were treated with N-acetylcysteine (NAC). Simultaneous, as well
      as sequential, treatment with NAC before imexon exposure resulted in protection
      of myeloma cells against imexon-induced cytotoxicity. Conversely, the glutathione
      synthesis inhibitor buthionine sulfoximine increased imexon cytotoxicity. These
      data suggest that imexon perturbs cellular thiols and induces oxidative stress
      leading to apoptosis in human myeloma cells.

PMID- 10930530
TI  - Expression, maturation, and rhodamine-based fluorescence assay of human cathepsin
      K expressed in CHO cells.
AB  - Cathepsin K is a cysteine protease that degrades type I human collagen during
      bone resorption. We have expressed the recombinant human cathepsin K in Chinese
      hamster ovary (CHO) cells as a pre-proenzyme and demonstrated that it is
      processed intracellularly to an active enzyme form and that only the proenzyme
      form is secreted. Immunofluorescence detection of cathepsin K in CHO cells
      resulted in discrete punctate distribution consistent with a lysosomal
      localization of the enzyme. With both extract and cell preparations of CHO cells
      expressing cathepsin K, [Z-Leu-Arg](2)-rhodamine was the best substrate for
      analyzing cathepsin K activity over background proteases. We have established a
      cellular-based assay to analyze cell-permeable inhibitors of cathepsin K and
      validated the assay with detection of intracellular versus extracellular
      activity, fluorescence-assisted cell sorter (FACS) analysis, and a selective
      cathepsin K inhibitor. The intracellular activity of cathepsin K was monitored by
      FACS analysis using the rhodamine substrate, which demonstrated an increased
      fluorescence over mock-transfected cells that was also inhibitable by (2S,3S)
      trans-epoxysuccinyl-L-leucylamido-3-methylbutane ethyl ester (E64d). A selective
      cathepsin K inhibitor, 1, 3-bis(CBZ-Leu-NH)-2-propanone, had an IC(50) of 134 nM
      in the CHO/Cat K cells, which is the same potency as that measured against a
      purified enzyme preparation of cathepsin K. Therefore, we have established a
      system to evaluate intracellular cathepsin K activity and inhibition by cell
      permeable inhibitors of this thiol protease.

PMID- 10930531
TI  - Induction of mitosis-mediated apoptosis by sodium arsenite in HeLa S3 cells.
AB  - Arsenic has been used effectively as a chemotherapeutic drug for the treatment of
      acute promyelocytic leukemia patients. Numerous studies have demonstrated that
      arsenic induces apoptosis in various cell types. In the present study, we showed
      that approximately 35% of arsenite-treated HeLa S3 cells arrested in mitosis.
      After release from arsenite treatment, more than 80% of arsenite-arrested mitotic
      cells subsequently underwent apoptosis, as indicated by anachronistic nuclear
      envelope reformation, DNA ladder occurrence, chromatin condensation, and
      activation of caspases 3 and 9. In exploring how these cells entered apoptosis
      mechanistically, we found an inverse correlation between mitotic indexes and
      apoptotic frequencies. As shown by using Percoll density gradient fractionation
      and flow cytometric analysis, the mitosis-mediated apoptosis induced by arsenite
      was accompanied by delayed cyclin B degradation and altered mitotic exit.
      Furthermore, treatment of arsenite-arrested mitotic cells with staurosporine or 2
      aminopurine resulted in a rapid degradation of cyclin B, moved these cells
      forward to interphase without cell division, and abrogated apoptosis. These
      results suggest that apoptosis occurs in arsenite-arrested mitotic cells that
      exit mitosis abnormally.

PMID- 10930532
TI  - Tyrosine phosphorylation of the delta-opioid receptor. Evidence for its role in
      mitogen-activated protein kinase activation and receptor internalization*.
AB  - The internalization of G-protein-coupled receptors (GPCRs), including the delta
      opioid receptor (delta-OR), has been shown to involve the phosphorylation of
      serine and threonine residues. However, recent studies suggest that these
      residues may not be the only ones phosphorylated in response to prolonged opioid
      exposure. Tyrosines also appear important for delta-OR signalling, but it remains
      unclear whether they undergo phosphorylation. We examined whether the delta-OR,
      stably expressed in Chinese hamster ovary (CHO-K1) cells, was tyrosine
      phosphorylated during prolonged agonist treatment. The epitope-tagged delta-OR
      was purified by immunoprecipitation, and the presence of phosphorylated tyrosines
      was detected using anti-phosphotyrosine antibodies. Tyrosine residues in the
      delta-OR were phosphorylated after exposure to the high-affinity agonist [d
      Thr(2)]-Leu-enkephalin-Thr (DTLET) in a time- and concentration-dependent manner.
      Tyrosine phosphorylation of the delta-OR appeared to require the actions of a Src
      like protein tyrosine kinase, since the Src inhibitor 4-amino-5-(4-methylphenyl)
      7-(t-butyl)-pyrazolo-[3,4-d]-pyrimidine (PP1) attenuated this response. PP1 also
      attenuated the DTLET-mediated activation of mitogen-activated protein kinase, as
      well as rapid delta-OR internalization, but not receptor down-regulation.
      Finally, only opioid agonists that induce receptor internalization via the
      clathrin-dependent endosomal pathway stimulated significant tyrosine
      phosphorylation of the delta-OR protein. Evidence is presented that the delta-OR
      is tyrosine-phosphorylated, and we suggest how this may have an active role in
      opioid receptor signalling and regulation.

PMID- 10930533
TI  - A single amino acid of the human and rat neurotensin receptors (subtype 1)
      determining the pharmacological profile of a species-selective neurotensin
      agonist.
AB  - The neurotensin (NT) receptor, subtype 1 (NTR1), is a 7-transmembrane-spanning
      receptor, forming 3 extracellular and 3 intracellular loops. Previously, we
      showed that the third outer loop (E3) is the binding site for NT and its analogs,
      several of which bind with higher affinity to rat NTR1 (rNTR1) than to human NTR1
      (hNTR1). In particular, NT34 [3,1'-naphthyl-l-Ala(11)]NT(8-13) has greater than
      60-fold higher affinity for rNTR1 (46 and 60 pM for transiently- and stably
      transfected cells, respectively) than for hNTR1 (2.8 and 5.8 nM for transiently-
      and stably-transfected cells, respectively) isolated from transfected cell
      membranes. Previously, our molecular modeling studies of rNTR1 and hNTR1 showed
      that the binding pocket in the human receptor for NT34 is smaller in volume from
      the bulky residue Tyr(339) in the pocket center, as compared with the
      corresponding residue Phe(344) in the rat binding pocket. Therefore, with site
      directed mutagenesis, we derived mutant forms of rNTR1(F344Y) and hNTR1(Y339F).
      Examination of the mutant receptors from membranal preparations of transfected
      cells in radioligand binding assays and with intact cells in functional assays
      (phosphatidyl-4,5-bisphosphate turnover) showed that the human-like rat receptor
      and the rat-like human receptor bound NT34 with a predicted reverse of binding
      compared with its binding to the wild-type receptors. These results strongly
      affirm our molecular modeling studies and demonstrate the importance of the study
      of even minor structural variations in proteins to determine the basis of
      significantly different drug responses, an area of focus for pharmacological
      research in the 21st century.

PMID- 10930534
TI  - In vitro effect of retinoids on calcineurin activity.
AB  - Calcineurin was shown previously to be inhibited by members of the tyrphostin
      family of tyrosine kinase inhibitors, with the most effective inhibition
      suggested to be caused by the presence of a conjugated side chain (Martin BL,
      Biochem Pharmacol 56: 483-488, 1998). Retinoids are a family of naturally
      occurring biomolecules having non-aromatic ring structures and conjugated side
      chains as substituents on the ring. Three oxidation states of the all-trans
      configuration of retinoids (retinol, retinal, and retinoic acid) were tested as
      effectors of calcineurin. Only retinoic acid was found to inhibit calcineurin
      effectively, with an IC(50) value of approximately 50 microM. Retinol and retinal
      caused less than 30% inhibition at concentrations up to 100 microM. All three
      retinoids caused some precipitation of reaction components: retinoic acid and
      retinal above 50 microM, and retinol above 250 microM. Bacterial alkaline
      phosphatase was not inhibited by the retinoids, indicating that metal centers
      alone are insufficient for significant inhibition by retinoic acid. An aromatic
      ring was not required for inhibition and may not provide additional inhibition,
      inasmuch as an aromatic analog of retinoic acid (acitretin) showed less effective
      inhibition. These data are consistent with the presence of conjugated,
      unsaturated groups enhancing the inhibition of calcineurin.

PMID- 10930535
TI  - 2,2',3,3',4,4'-Hexahydroxy-1,1'-biphenyl-6,6'-dimethanol dimethyl ether (HBDDE)
      induced neuronal apoptosis independent of classical protein kinase C alpha or
      gamma inhibition.
AB  - Protein kinase C (PKC) isozymes constitute a family of at least 12 structurally
      related serine-threonine kinases that are differentially regulated and localized,
      and are presumed to mediate distinct intracellular functions. To explore their
      roles in intact cells, investigators are developing cell-permeable, isoform
      selective inhibitors. 2,2',3,3',4,4'-Hexahydroxy-1, 1'-biphenyl-6,6'-dimethanol
      dimethyl ether (HBDDE) is reported to be a selective inhibitor of PKC alpha and
      gamma with IC(50) values of 43 and 50 microM, respectively, using an in vitro
      assay. However, data examining the potency and selectivity of HBDDE in intact
      cells are lacking. Employing rodent cerebellar granule neurons as a model system,
      we investigated the effects of HBDDE using cell survival as a functional end
      point. HBDDE induced an apoptotic form of cell death that was dependent upon
      protein synthesis and included activation of a terminal executioner of apoptosis,
      caspase 3. The concentration of HBDDE required for half-maximal cell death was
      less than 10 microM ( approximately 5-fold less than the reported IC(50) values
      for PKC alpha and gamma in vitro). Furthermore, HBDDE induced apoptosis even
      after phorbol-ester-mediated down-regulation of PKC alpha and gamma, indicating
      that this effect is independent of these isoforms. Consistent with this, 2-[1-(3
      dimethylaminopropyl) indol-3-yl]-3-(indol-3-yl)-maleimide (GF 109203X), a general
      inhibitor of all classical and some novel PKCs, did not interfere with survival.
      Thus, HBDDE should not be used as an isoform-selective inhibitor of PKC alpha or
      gamma in intact cells. Nevertheless, identification of its target in granule
      neurons will provide valuable information about survival pathways.

PMID- 10930536
TI  - An investigation into the formation of N- [2-(dimethylamino)ethyl]acridine-4
      carboxamide (DACA) and 6-[2-(dimethylamino)ethylamino]- 3-hydroxy-7H-indeno[2, 1
      C]quinolin-7-one dihydrochloride (TAS-103) stabilised DNA topoisomerase I and II
      cleavable complexes in human leukaemia cells.
AB  - The antitumour agents DACA (XR5000; N-[2-(dimethylamino)ethyl]acridine-4
      carboxamide) and TAS-103 (6-[2-(dimethylamino)ethylamino]-3-hydroxy-7H-indeno[2,
      1-c]quinolin-7-one dihydrochloride) have been shown to inhibit two essential
      nuclear enzymes in vitro, DNA topoisomerase I and DNA topoisomerase (topo) II. To
      examine whether DACA or TAS-103 stabilise topo I, topo IIalpha, and topo IIbeta
      cleavable complexes in human leukaemia CCRF-CEM cells, the TARDIS assay (trapped
      in agarose DNA immunostaining) was used. This assay can reveal drug-stabilised
      topo-DNA complexes formed in situ in individual cells. The results showed that
      both DACA and TAS-103 can stabilise topo IIalpha cleavable complexes in these
      cells. Topo IIbeta cleavable complexes were also formed, but only at high
      concentrations of DACA and TAS-103. The effect on topo I was less clear, with TAS
      103 showing only low levels of cleavable complex formation and DACA having no
      detectable effect under these assay conditions. This is in contrast to the
      purified enzyme cleavable complex assay, where both DACA and TAS-103 poisoned
      topo I. Although both DACA and TAS-103 show a preference for topo IIalpha in
      whole cells using the TARDIS assay, the formation of low levels of topo I or topo
      IIbeta cleavable complexes may still play a role in cell death.

PMID- 10930537
TI  - Prevention of etoposide-induced apoptosis by proteasome inhibitors in a human
      leukemic cell line but not in fresh acute leukemia blasts. A differential role of
      NF-kappab activation.
AB  - Recent research indicates that the proteasome is one of the non-caspase proteases
      involved in apoptotic signaling pathways. Nuclear factor-kappaB (NF-kappaB)
      activation, one of the key factors in apoptosis, can be prevented through
      abrogation of IkappaBalpha degradation by proteasome inhibition. We have
      investigated the effects of the proteasome inhibitors carbobenzoxyl-L-leucyl-L
      leucyl-L-leucinal (MG132) and N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL)
      on apoptosis and NF-kappaB activation induced by etoposide, using a human
      leukemia cell line (U937) and leukemia blasts freshly isolated from patients with
      acute leukemia. Pretreatment of U937 cells with MG132 or LLnL inhibited etoposide
      induced morphological apoptosis and caspase-3 activation. Furthermore, MG132 or
      LLnL prevented NF-kappaB activation and IkappaBalpha degradation, but not
      IkappaBalpha phosphorylation at Ser32. Other inhibitors of NF-kappaB activation,
      including pyrrrolidine dithiocarbamate (an antioxidant) and the peptide SN50 (an
      inhibitor of translocation of activated NF-kappaB into the nucleus), also
      attenuated etoposide-induced apoptosis. In leukemia blasts, although proteasome
      inhibitors suppressed NF-kappaB activation induced by etoposide, they were unable
      to prevent morphological apoptosis. Moreover, proteasome inhibitors by themselves
      caused apoptosis in leukemia blasts at the concentrations employed in this study.
      These results suggest that the role that NF-kappaB plays in apoptosis induced by
      etoposide in a human leukemia cell line may be different from the role it plays
      in freshly isolated leukemia blasts.

PMID- 10930540
TI  - 5-phenylthioacyclouridine: a potent and specific inhibitor of uridine
      phosphorylase.
AB  - 5-Phenylthioacyclouridine (PTAU or 1-[(2-hydroxyethoxy)methyl]-5
      phenylthiouracil) was synthesized as a highly specific and potent inhibitor of
      uridine phosphorylase (UrdPase, EC 2.4.2.3). PTAU has inhibition constant (K(is))
      values of 248 and 353 nM towards UrdPase from mouse and human livers,
      respectively. PTAU was neither an inhibitor nor a substrate for thymidine
      phosphorylase (EC 2.4.2.4), uridine-cytidine kinase (EC 2. 7.1.48), thymidine
      kinase (EC 2.7.1.21), dihydrouracil dehydrogenase (EC 1.3.1.2), orotate
      phosphoribosyltransferase (EC 2.4.2.10), or orotidine 5'-monophosphate
      decarboxylase (EC 4.1.2.23), the enzymes that could utilize the substrate
      (uridine or thymidine) or products (uracil or thymine) of UrdPase. Different
      isomers of 5-tolylthiouracil also were synthesized and tested as inhibitors of
      UrdPase. The meta-substituted isomer was 3- to 4-fold more potent as an inhibitor
      of UrdPase than the para- or ortho-substituted isomers. These data indicate that
      the hydrophobic pocket in the active site of UrdPase adjacent to the 5-position
      of the pyrimidine ring can accommodate the meta-substituted 5-phenyluracils
      better than the other isomers, leading to improved inhibition. Therefore, it is
      anticipated that the potency of PTAU can be increased further by the addition of
      certain hydrophobic groups at the meta position of the phenyl ring. PTAU has
      potential usefulness in the therapy of cancer and AIDS as well as other
      pathological and physiological disorders that can be remedied by the
      administration of uridine.

PMID- 10930538
TI  - BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells.
AB  - We have previously described a mitoxantrone-resistant MCF7 cell line that is
      cross-resistant to topotecan, 7-ethyl-10-[4-(1-piperidino)-1
      piperidino]carbonyloxy-camptothecin (CPT-11), and 9-aminocamptothecin, but not to
      camptothecin. A novel mechanism that resulted in decreased topotecan accumulation
      in MCF7/MX cells was proposed (Yang et al. Cancer Res 55: 4004-4009, 1995). We
      now have developed a topotecan-resistant cancer cell line from wild-type MCF7
      cells. MCF7/TPT300 cells were 68.9-fold resistant to topotecan, 68.3-fold to 10
      hydroxy-7-ethylcamptothecin (SN-38), and 116-fold to mitoxantrone, but only 4.1
      fold to camptothecin. Topotecan efflux was increased in MCF7/TPT300 cells
      compared with MCF7/WT cells, and this increase was reversed upon ATP depletion by
      sodium azide, suggesting an energy-dependent drug efflux mechanism. However,
      MCF7/TPT300 cells did not overexpress P-glycoprotein or the multidrug resistance
      associated protein (MRP1). In contrast, overexpression of the breast cancer
      resistance protein (BCRP/MXR/ABCP) was observed in MCF7/TPT300 cells as well as
      DNA topoisomerase I down-regulation. Our data suggest that enhanced topotecan
      efflux contributes partly to topotecan resistance in MCF7/TPT300 cells, possibly
      mediated by BCRP/MXR/ABCP.

PMID- 10930539
TI  - Early stimulation of acidification rate by novel cytotoxic pyridyl
      cyanoguanidines in human tumor cells: comparison with m-iodobenzylguanidine.
AB  - CHS 828, a newly recognized pyridyl cyanoguanidine, has shown promising antitumor
      activity both in vitro and in vivo and is presently in early phase I clinical
      trial in collaboration with EORTC. In this study, the effects of CHS 828 and a
      series of analogues on extracellular acidification and cytotoxicity were compared
      with those of m-iodobenzylguanidine (MIBG) in human tumor cells. The
      extracellular acidification rate was measured using the Cytosensor
      microphysiometer, and determination of cytotoxicity and proliferation was [(14)C]
      performed by the fluorometric microculture cytotoxicity assay (FMCA) and
      measurement of [(14)C]thymidine and leucine uptake. CHS 828 significantly
      increased the acidification rate during the first 15-24 hr in a concentration
      dependent manner. This effect was abolished by removal of glucose from the
      medium, substituted with 10 mM of pyruvate, indicating stimulated glycolysis as
      the source of the increased acidification rate. However, CHS 828 induced
      cytotoxicity at concentrations well below those that affected the rate of
      acidification; when a series of closely related pyridylguanidine analogues were
      tested and compared, no apparent relationship between cytotoxicity and
      acidification could be discerned. Furthermore, comparable increases in the
      acidification rate were evident in one subline with high-grade resistance to the
      cytotoxic actions of CHS 828. The results indicate that CHS 828 may share the
      inhibitory actions of MIBG on mitochondrial respiration with a subsequent
      increase in glycolysis and acidification rate. However, this mechanism of action
      appears neither necessary nor sufficient to fully explain the cytotoxic actions
      of CHS 828 in human tumor cells, actions which remain to be mechanistically
      clarified.

PMID- 10930541
TI  - A transgenic mouse expressing human CYP1A2 in the pancreas.
AB  - A transgenic mouse line expressing the human cytochrome P450 CYP1A2 in the
      pancreas under the control of the mouse elastase promoter was established. The
      expression of CYP1A2 was specific to the transgenic pancreas and was not found in
      the control wild-type mouse pancreas. The level of CYP1A2 expressed in pancreatic
      microsomes from transgenic mice was comparable to that of the endogenously
      expressed CYP1A2 protein in the liver, as judged by western blotting analyses.
      Estrone metabolism was used to determine the activity of CYP1A2 expressed in the
      pancreas of the transgenic mouse. The transgenic pancreas exhibited almost one
      third to one-half of the activity of wild-type or CYP1A2 transgenic mouse liver,
      whereas the wild-type pancreas demonstrated no activity. The addition of NADPH
      cytochrome P450 oxidoreductase to the reaction mixture containing pancreatic
      microsomes from the transgenic mice did not increase the estrone metabolism
      activity significantly. This transgenic mouse line provides another useful tool
      to study human CYP1A2 and its relation to chemical toxicity and carcinogenesis.

PMID- 10930542
TI  - Activation of phospholipase C by cholecystokinin receptor subtypes with different
      G-protein-coupling specificities in hormone-secreting pancreatic cell lines.
AB  - Phospholipase C (PLC) activity was investigated by stimulation of membrane
      preparations obtained from insulin (beta-TC3)-, somatostatin (Rin 1027-B2)-, and
      glucagon (INR1-G9)-producing pancreatic cell lines using the non-hydrolyzable GTP
      analogue GTPgammaS alone, the C-terminal octapeptide cholecystokinin (CCK-8), or
      gastrin. All compounds caused a significant 2- to 4.4-fold stimulation of PLC
      activity in the different cell lines, which was diminished by the non
      hydrolyzable GDP analogue GDPbetaS. CCK receptor subtypes were characterized by
      radioligand binding experiments. High-affinity binding sites for tritiated CCK(A)
      receptor antagonist L-364,718 (K(d) = 0.24 nM) and tritiated CCK(B) receptor
      antagonist L-365,260 (K(d) = 0.13 nM) were only present in Rin 1027-B2 cells.
      High-affinity binding sites for both ligands were not found in beta-TC3 or INR1
      G9 cells. Competition binding experiments with non-labeled CCK receptor
      antagonists CR 1505 (CCK(A) receptor-selective) and CR 2945 (CCK(B) receptor
      selective), as well as microphysiometry experiments, resulted in the same
      receptor distribution. Reverse transcriptase-polymerase chain reaction confirmed
      the CCK receptor distribution pattern for Rin 1027-B2 cells, but in addition
      showed the existence of CCK(B) receptors in beta-TC3 cells. Immunoblocking
      experiments with C-terminal antibodies against different G-protein alpha-subunits
      demonstrated inhibition of CCK-stimulated PLC activity in beta-TC3 cells by
      G(q/11)alpha antiserum (70%), in Rin 1027-B2 cells by G(q/11)alpha antiserum
      (70%) and G(i)-3alpha antiserum (23%), and in INR1-G9 cells by G(q/11)alpha
      antiserum (60%) and G(o)alpha antiserum (45%). We conclude that CCK receptor
      subtypes with different G-protein-coupling specificities to PLC are present in
      the different hormone-secreting cells of the endocrine pancreas.

PMID- 10930543
TI  - Opioid induced non-photic phase shifts of hamster circadian activity rhythms.
AB  - The phase of the circadian pacemaker in hamsters can be shifted by the
      application of certain non-photic stimuli late in the subjective day. A
      projection from the intergeniculate leaflet of the thalamus to the circadian
      pacemaker in the suprachiasmatic nucleus is believed to mediate some types of non
      photic phase-shifting stimuli. In hamsters, this projection is immunoreactive to
      both Neuropeptide Y and enkephalin. Previous work in other laboratories has shown
      that Neuropeptide Y administration is capable of phase shifting circadian rhythms
      without the application of light. The present study was undertaken to determine
      if enkephalinergic compounds likewise have the ability to non-photically phase
      shift hamster activity rhythms. Hamsters were maintained under conditions of
      constant darkness and circadian wheel running activity was recorded. Agonists and
      antagonists selective for kappa, mu, and delta opioid receptors were systemically
      applied without light to hamsters at circadian times 8 and 10 to determine if
      they were able to elicit phase shifts in wheel running activity rhythms. Of the
      compounds tested, only the delta opioid agonist BW373U86 significantly affected
      circadian phase. BW373U86 phase advanced hamster wheel running activity rhythms
      by approximately 45 min, although total activity levels following drug
      application were not significantly affected. Changes in the amount of wheel
      running activity were detected after administration of some mu and kappa opioids,
      although the circadian phase was not altered. These results indicate that
      enkephalin-mimetic delta opioid agonists are capable of producing non-photic
      phase shifts in hamster activity rhythms, and that opioids can independently
      affect circadian phase and activity levels in hamsters.

PMID- 10930544
TI  - Intracerebroventricular injection of prostaglandin E(1) changes concentrations of
      biogenic amines in the posterior hypothalamus of the rat.
AB  - Since the posterior hypothalamus (PH) plays a key role in the control of body
      temperature, the aim of this study was to evaluate the changes in adrenaline,
      noradrenaline and dopamine levels in the PH during the hyperthermia induced by
      prostaglandin E(1) (PGE(1)). The concentration of adrenaline, noradrenaline and
      dopamine in the PH, the firing rate of the sympathetic nerves innervating
      interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (T(IBAT)
      and T(C)) were monitored in 12 urethane-anaesthetized male Sprague-Dawley rats
      before and after an intracerebroventricular injection of 500 ng PGE(1) dissolved
      in 2 microl of 0.9% NaCl saline solution or only saline. The catecholamines were
      collected using a microdialysis probe and quantified by HPLC. The results showed
      that PGE(1) caused a significant increment in the concentration of adrenaline
      from 15. 83+/-2.69 to 34.95+/-3.9 ng ml(-1) and of dopamine from 35.15+/-4.48 to
      55.68+/-6.21 ng ml(-1). A significant decrease in the level of noradrenaline from
      18.75+/-2.05 to 8.56+/-2.26 ng ml(-1) was registered. The firing rate of
      sympathetic nerves to IBAT was increased from 100+/-0% to 204.83+/-15.22% by
      PGE(1). T(IBAT) and T(C) rose respectively from 36.91+/-0.15 degrees C to 38.88+/
      0.29 degrees C, and from 36.7+/-0.15 degrees C to 38.13+/-0.36 degrees C after
      the injection of PGE(1). The changes in adrenaline and noradrenaline occurred
      during the first 20 min as did the changes in temperature and firing rate, while
      the change in dopamine was delayed until 21-60 min after the PGE(1) injection. No
      significant change of analyzed variables was found in the control rats. These
      findings suggest that these biogenic amines of the PH are involved in the control
      of the sympathetic and thermogenic changes induced by PGE(1).

PMID- 10930545
TI  - Preferential resistance of dopaminergic neurons to glutathione depletion in a
      reconstituted nigrostriatal system.
AB  - Depletion of glutathione in the substantia nigra is one of the earliest changes
      observed in Parkinson's disease (PD), and could initiate dopaminergic neuronal
      degeneration. Nevertheless, we have previously demonstrated that mesencephalic
      dopaminergic neurons in primary monolayer cultures are more resistant to the
      toxicity of glutathione depletion than nondopaminergic neurons. To extend this
      finding to a system that more closely resembles the in vivo situation, we
      characterized the effects of glutathione depletion on reaggregate cultures
      derived from ventral mesencephalic and their striatal target neurons, as well as
      supporting elements including glia. Dopaminergic neurons were found to be more
      resistant to the toxicity of buthionine-(S,R)-sulfoximine, an inhibitor of
      glutathione synthesis, than other nigrostriatal neurons, while striatal target
      cells exhibited an intermediate susceptibility when examined after 48 h.
      Glutathione depletion, however, decreased the intracellular content of
      catecholamines after 48 h and eventually led to the loss of dopaminergic neurons
      after 7 days. Our data indicate that the intrinsic resistance of dopaminergic
      neurons to the toxicity of glutathione depletion occurs in a variety of
      experimental paradigms, and suggest that global glutathione depletion alone is
      unlikely to account for the selective loss of dopaminergic neurons in PD. Rather,
      it is more likely that either the selective loss of glutathione from dopaminergic
      neurons, or the combination of glutathione loss with other insults contributes to
      the preferential death of dopaminergic neurons in PD.

PMID- 10930546
TI  - 2R,4R-4-Aminopyrrolidine-2,4-dicarboxylate (APDC) attenuates cortical EPSPs.
AB  - We studied the effect of the Type II metabotropic glutamate receptor (mGluR 2,3)
      agonist APDC on the response of neurons in slices of rat visual cortex. In all
      cortical layers, APDC attenuated the EPSP produced by stimulation of the
      predominant excitatory input. This EPSP attenuation was seen in both younger and
      older rat slices and was present with G-protein blockade in the cell recorded,
      demonstrating that it was a presynaptic effect. Further, this EPSP attenuation
      was blocked by the mGluR 2,3 antagonist EGLU. A postsynaptic depressive effect of
      APDC on the NMDA response was seen in layers 2 and 3, but not in layers 5 and 6.
      Thus, the predominant action of Type II mGluRs in the visual cortex is a
      presynaptic reduction of glutamate release which persists through development.
      This regulation may be important in the setting of excitatory tone in visual
      cortex and in the extraction/processing of visual information.

PMID- 10930547
TI  - The kinetics of a non-inactivating K(+) current in alphaT3-1 pituitary
      gonadotropes is not affected by holding potential.
AB  - The non-inactivating K(+) currents in alphaT3-1, a gonadotroph cell line, were
      recorded in the presence of low intracellular free calcium concentration. The
      activation kinetics of the whole-cell currents and the gating charge measured
      from holding potential (V(HOLD)) of -10 mV, V(HOLD)=-80 mV in presence of 4-AP (4
      aminopyridine), and V(HOLD)=-10 mV with a hyperpolarizing prepulse to -80 mV were
      similar. No difference was observed in the onset of currents elicited from the
      hyperpolarizing potentials, suggesting deviation from the Cole-Moore prediction
      of increase in the delay of current onset with increasing hyperpolarization. The
      data suggests that the channel opens with at least one rate-limiting voltage
      dependent step, which may imply that the position of the voltage sensor is
      unaffected by hyperpolarization.

PMID- 10930548
TI  - Potentiated and preferential effects of combined paraquat and maneb on
      nigrostriatal dopamine systems: environmental risk factors for Parkinson's
      disease?
AB  - The absence of any compelling basis for a heritable basis of idiopathic
      Parkinson's disease (PD) has focused attention on environmental exposures as
      causative agents. While the herbicide paraquat has repeatedly been implicated,
      its impact on dopamine systems following systemic exposures is equivocal. The
      restricted focus on paraquat also ignores the extensive geographical overlap of
      its use with other agrichemicals known to adversely impact dopamine systems,
      including ethylenebisdithiocarbamate fungicides such as maneb. The present study
      sought to determine whether combined exposures to paraquat and maneb would
      produce additive effects and support a multiple-hit environmental contribution to
      PD. C57BL/6 mice were exposed to either paraquat (5-10 mg/kg) or maneb (15-30
      mg/kg) i.p. alone or in combination once a week for 4 weeks. Sustained decreases
      in motor activity immediately following injections were consistently observed
      only with combined exposures, with activity levels returning to control values 24
      h later. Concurrently, levels of dopamine and metabolites and dopamine turnover
      were increased immediately post-injection only by combined exposures, and
      returned to control levels or below within 48 h. Reductions in tyrosine
      hydroxylase immunoreactivity, measured 3 days after the last injection, resulted
      only from combined exposure and were detected in dorsal striatum, but not in the
      nucleus accumbens. The fact that combined exposures resulted in potentiated
      effects that appear to target nigrostriatal dopamine systems suggests that these
      combinations may be important environmental risk factors for Parkinsonism. These
      findings also raise questions about the adequacy of current risk assessment
      guidelines for these chemicals which are based on effect levels derived from
      exposures to single agents.

PMID- 10930549
TI  - Estradiol protects against injury-induced cell death in cortical explant
      cultures: a role for estrogen receptors.
AB  - Estradiol has been shown to exert trophic and protective actions in the brain.
      Our laboratory has shown that in vivo, low physiological levels of estradiol
      protect the female rat brain against ischemic injury. In the present study, we
      used organotypic cortical explant cultures to begin to decipher the mechanisms of
      estradiol's actions. Injury was induced by exposure to kainic acid or potassium
      cyanide/2-deoxyglucose (KCN/2-DG) for varying lengths of time, and cell death was
      monitored by LDH release at 2, 6, 12, 24, 48, 72 and 96 h after injury. We found
      that exposure to 1 mM KCN/2 mM 2-DG for 2 h produced consistent delayed cell
      death that was detectable by 24 h. The presence of 17beta-estradiol (E2) during
      the 7 days prior to injury significantly reduced the extent of cell death;
      whereas, administration of E2 at the time of injury did not protect. The
      protective effects of estradiol were dose dependent. Low doses of E2 (1, 10, and
      30 nM) significantly reduced cell death; however, higher concentrations of E2
      (>60 nM) had no protective effect. The observations that low levels of E2 protect
      against cell death, and that pretreatment is required suggest that the protective
      actions of estradiol may involve estrogen receptors. Therefore, we examined the
      ability of 17alpha-estradiol, which does not efficiently activate the estrogen
      receptor, and the addition of the estrogen receptor antagonist, ICI 182,780, to
      influence the extent of cell death induced by KCN/2-DG. 17alpha-Estradiol failed
      to protect, and ICI 182,780 prevented E2 from protecting against cell death.
      Furthermore, E2 pretreatment is required for more than 24 h to be
      neuroprotective. Our results clearly show that in cortical explant cultures,
      estradiol protects cells against ischemic injury, and suggest that these
      protective actions involve estrogen receptors.

PMID- 10930550
TI  - Melatonin attenuates neuronal NADPH-d/NOS expression in the hypoglossal nucleus
      of adult rats following peripheral nerve injury.
AB  - Oxidative stress and massive production of nitric oxide (NO) have been implicated
      in the neuropathogenesis following peripheral nerve injury. This study was aimed
      to ascertain whether melatonin would exert its neuroprotective effect on the
      lesioned hypoglossal neurons after peripheral axotomy, since it is known to
      reduce the oxidative damage in a variety of experimental neuropathologies in
      which NO is involved. Right-sided hypoglossal nerve transection was performed in
      adult rats following which the animals were given two different doses of
      melatonin administered intraperitoneally for 3, 7, 14, 21 and 30 successive days.
      Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry
      and neuronal nitric oxide synthase (nNOS) immunohistochemistry were carried out
      to detect the neuronal NADPH-d/NOS expression in the hypoglossal nucleus (HN). At
      various time intervals following axotomy, the neurons in the affected HN were
      induced to express NADPH-d/NOS reactivity on the lesioned side peaking at 14
      days. However, the enzyme expression was markedly depressed by melatonin
      treatment in a dose-dependent manner in terms of frequency of labelled neurons
      and staining intensity. It is suggested that the suppressive effect of melatonin
      on NADPH-d/NOS expression may be attributed to its antioxidant properties. Hence,
      in consideration of therapeutic strategies for reducing the oxidative stress
      following peripheral nerve injury, melatonin may prove to be beneficial.

PMID- 10930551
TI  - Involvement of cystatin C in oxidative stress-induced apoptosis of cultured rat
      CNS neurons.
AB  - Oxidative stress is involved in neuronal degeneration in cerebrovascular injury,
      neuropathology and aging. When rat CNS neurons were cultured in a high (50%)
      oxygen atmosphere, the neurons died. This high oxygen-induced cell death showed
      features of apoptotic cell death, characterized by DNA fragmentation, and was
      blocked by inhibitor of protein synthesis. We found that cystatin C and HuC mRNA,
      the products of which are an inhibitor of cysteine proteases and an RNA binding
      protein, respectively, were up-regulated in neurons cultured in the high oxygen
      atmosphere. In the present study, we focused on cystatin C. Cystatin C protein
      levels were also increased in neurons cultured in the high oxygen atmosphere. In
      situ hybridization with an RNA probe for rat cystatin C and immunocytochemistry
      with anti-human cystatin C antibody showed that microtubule-associated protein 2
      (MAP2)-positive neurons expressed cystatin C mRNA and protein, respectively, in
      the high oxygen atmosphere. These results indicated that oxidative stress
      stimulates an increase in cystatin C expression in cultured neurons, and that
      cystatin C might have important roles in regulation of apoptosis elicited by
      oxidative stress.

PMID- 10930552
TI  - Lesion of the subthalamic nucleus or globus pallidus does not cause chaotic
      firing patterns in basal ganglia neurons in rats.
AB  - The basal ganglia appears to play an important role in behavioral selection. One
      model (Berns and Sejnowski's) of basal ganglia function argues that the
      subthalamic nucleus plays a critical role in this selection process and predicts
      that the subthalamic nucleus prevents the basal ganglia and its re-entrant
      circuits with the thalamus and cerebral cortex from developing chaotic
      oscillations. We tested this prediction by generating three-dimensional
      sequential interval state space plots of the spike trains from 684 globus
      pallidus, substantia nigra pars reticulata and subthalamic neurons recorded in
      intact, subthalamic lesioned and globus pallidus lesioned rats, neurons which had
      previously been analyzed with more standard statistical methods. Only 1 neuron (a
      globus pallidus neuron in a subthalamic lesioned rat) of the 684 showed a chaotic
      attractor. In no case did subthalamic nucleus lesion induce a chaotic firing
      pattern elsewhere in the basal ganglia.

PMID- 10930553
TI  - Effects of disulfide bonds formed during isolation process on the structure of
      the postsynaptic density.
AB  - The biochemical, morphological and structural properties of rat postsynaptic
      densities (PSDs) isolated under conditions where disulfide bond formation was
      allowed or curtailed were studied here. Biochemical analyses revealed that the
      isolated PSDs were composed by a similar set of proteins regardless of the
      differences in their isolation processes. The PSDs isolated under the conditions
      where disulfide bond formation was curtailed were more easily dissociated by
      treatments with urea, guanidine hydrochloride and deoxycholate than the PSDs
      isolated under conditions where disulfide bond formation was allowed.
      Consistently, the structure of the PSDs isolated under the former condition
      appeared to be more fragmented than those isolated under the latter condition, as
      revealed by electron microscopy. The results indicate that the disulfide bonds
      formed during the isolation process significantly tighten the PSD structure and
      further suggest that the PSD in vivo is a protein aggregate whose constituent
      proteins be held together primarily by non-covalent interactions.

PMID- 10930554
TI  - SNRK, a member of the SNF1 family, is related to low K(+)-induced apoptosis of
      cultured rat cerebellar granule neurons.
AB  - When cerebellar granule neurons obtained from 11-day-old rats were cultured first
      in high K(+) medium for 4 days, followed by culture in low K(+) medium, the
      neurons underwent apoptosis and died. This cell death was prevented by
      actinomycin D, an inhibitor of RNA synthesis. Commitment time of the protective
      effect of RNA synthesis inhibition on the cell death was examined by adding
      actinomycin D at various time points after the switch to the low K(+) medium.
      More than 50% of the cells died when actinomycin D was added 3 h after changing
      to the low K(+) medium. To identify what kinds of newly synthesized genes are
      involved in regulation of the low K(+)-induced death, we performed PCR-based
      differential subtraction analysis using RNA prepared from the cultured neurons 0
      and 3 h after changing to low K(+) medium. We isolated a clone that showed an
      increase in its mRNA level after changing to the low K(+) medium. This clone
      encoded the 3' untranslated region of SNRK, a serine/threonine kinase. Tissue
      distribution analysis showed that the mRNA was expressed mainly in the brain and
      testis. Developmental analysis in the brain showed that the mRNA expression
      increased in an age-dependent manner until P28, and was slightly decreased in
      adults. In situ hybridization analysis showed that the mRNA was expressed
      throughout the brain. The mRNA was shown to be expressed in neurons by double
      staining with anti-MAP2 antibody. In addition, anti-N-terminal SNRK antibody
      stained the nuclei of cultured rat cerebellar granule neurons. These results
      suggested that SNRK may be involved in regulation of low K(+)-induced apoptosis
      of cultured cerebellar granule neurons.

PMID- 10930555
TI  - Effect of chronic food restriction on Fos-like immunoreactivity (FLI) induced in
      rat brain regions by intraventricular MK-801.
AB  - The noncompetitive NMDA antagonist, MK-801, produces stimulant and rewarding
      effects that are mediated by a combination of dopamine-dependent and -independent
      mechanisms. It was recently demonstrated that, similar to amphetamine, the
      rewarding and locomotor effects of intraventricular (i.c.v.) MK-801 are
      potentiated by chronic food restriction. Because food restriction also increases
      c-Fos expression induced by i.c.v. amphetamine in several subcortical dopamine
      (DA) terminal areas, Fos-like immunoreactivity (FLI) induced by i.c.v. MK-801 was
      evaluated in an effort to identify responses that are common to amphetamine and
      MK-801 and similarly augmented by food restriction. Unlike amphetamine, MK-801
      did not increase FLI in caudate-putamen, bed nucleus of the stria terminalis, or
      ventral pallidum. Similar to amphetamine, MK-801 increased FLI in cingulate
      cortex, central nucleus of the amygdala and nucleus accumbens (NAC) core, but in
      none of these areas was the response augmented by food restriction. In medial
      prefrontal cortex, retrosplenial cortex, and NAC shell, however, MK-801 induced
      FLI that was augmented by food restriction. An effect that is common to
      amphetamine and MK-801 is the augmentation of FLI by food restriction in NAC
      shell. It is therefore suggested that increased releasability of DA, or
      upregulation of the D-1 receptor linked signal transduction pathway, in NAC shell
      may mediate the enhanced behavioral sensitivity of food-restricted subjects to
      drugs of abuse.

PMID- 10930556
TI  - The rat vertex-middle latency auditory-evoked potential as indicator of
      anaesthetic depth: a comparison with evoked-reflex testing.
AB  - We investigated whether components from the rat Vx-MLAEP could be used to assess
      depth of anaesthesia induced by propofol. Propofol decreased MLAEP amplitudes and
      increased latencies. We propose that the P(16)-N(22) wave in the rat MLAEP is
      similar to the human P1, and that recovery of this wave during propofol
      anaesthesia correlates with behavioural measures of the regaining of
      consciousness.

PMID- 10930557
TI  - Endomorphin-1 and endomorphin-2 induce the expression of c-FOS immunoreactivity
      in the rat brain.
AB  - Using FOS immunoreactivity (FOSir) as an anatomical marker of neuronal
      activation, we examined the effects of intracerebroventricular (i.c.v.)
      injections of endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in the rat brain to
      determine the sites of action of these two mu-opioid ligands. Radiant heat tail
      flick latency, as a measure of behavioral effects, was prolonged by either EM-1
      or EM-2 administration. Dose-dependent EM-1- and EM-2-induced FOSir were observed
      in various nuclei throughout the rostral-caudal axis of the rat brain. While
      there was some overlap, EM-1-induced FOSir was more prevalent than EM-2. The
      pattern of EM-induced FOSir was similar to the distribution of EM
      immunoreactivity (EMir). However, some sites with little or no detectable EMir
      exhibited FOSir, while other nuclei with marked EMir showed only sparse FOSir. EM
      induced FOSir was correlated with mu-opioid receptor location in most brain
      areas. However, EM-induced FOSir was absent in the caudate putamen and the
      accumbens nucleus, both areas of high mu-opioid receptor density.

PMID- 10930558
TI  - Receptor subtype and dose dependence of dexmedetomidine-induced accumulation of
      [14C]glutamine in astrocytes suggests glial involvement in its hypnotic-sedative
      and anesthetic-sparing effects.
AB  - Dexmedetomidine, a selective alpha(2)-adrenergic agonist, increases accumulation
      of [14C]glutamine and its labeled metabolites in primary cultures of mouse
      astrocytes. The concentration dependence is biphasic and identical to that
      previously described for dexmedetomidine's effect on free cytosolic calcium
      concentration ([Ca(2+)](i)) in astrocytes, and both effects are exerted on the
      alpha(2A) subtype of the alpha(2) receptor, suggesting a Ca(2+)-mediated effect.
      The concentration corresponding to the most potent effect is similar to that with
      which dexmedetomidine exerts its anesthetic-sparing activity in vivo, and the
      second peak corresponds to its hypnotic-sedative effect. It is suggested that
      both effects may be caused by decreased glutamatergic neurotransmission,
      secondary to reduced availability of glutamine as a glutamate precursor in
      glutamatergic neurons.

PMID- 10930559
TI  - Functional evidence for the rapid desensitization of 5-HT(3) receptors on vagal
      afferents mediating the Bezold-Jarisch reflex.
AB  - The aim of this study was to determine whether 5-hydroxytryptamine (5-HT)(3)
      receptors on cardiopulmonary afferents mediating the Bezold-Jarisch reflex (BJR)
      desensitize upon repeated exposure to selective agonists. BJR-mediated falls in
      heart rate, diastolic arterial blood pressure and cardiac output elicited by the
      5-HT(3)-receptor agonists, phenylbiguanide (100 microg/kg, i.v.) or 2-methyl-5-HT
      (100 microg/kg, i.v.), progressively diminished upon repeated injection in
      conscious rats. The BJR responses elicited by 5-HT (40 microg/kg, i.v.) were
      markedly reduced in rats which had received the above injections of
      phenylbiguanide or 2-methyl-5-HT whereas the BJR responses elicited by L-S
      nitrosocysteine (10 micromol/kg, i.v.) were similar before and after the
      injections of the 5-HT(3) receptor agonists. These findings suggest that
      tachyphylaxis to 5-HT(3) receptor agonists may be due to the desensitization of 5
      HT(3) receptors on cardiopulmonary afferents rather than the impairment of the
      central or peripheral processing of the BJR.

PMID- 10930560
TI  - Distribution of somatostatin in the brain and of somatostatin and thyrotropin
      releasing hormone in peripheral tissues of the chicken.
AB  - Our research group recently presented the distribution of thyrotropin-releasing
      hormone (TRH) in the chicken brain. In this study we measured somatostatin (SRIH)
      concentrations in different brain parts and nuclei. The distribution of SRIH and
      TRH in peripheral tissues was also studied. Although the highest SRIH content was
      found in endocrine areas like diencephalon and median eminence (ME), high levels
      were also recorded in brain stem and several hypothalamic nuclei which do not
      project to the ME. SRIH immunoreactivity was also found within the pituitary. In
      peripheral tissues, SRIH was mainly present in gonads, thyroid and intestine. Low
      amounts were found in duodenum, kidney, heart and lung. SRIH concentrations were
      barely detectable (liver, blood cells) or undetectable (muscle, skin, spleen) in
      other peripheral tissues investigated. Although TRH was found in all tissues
      collected, it was also most abundant in brain, pituitary, thyroid and gonads. Our
      results suggest that also in the chicken SRIH and TRH are implicated in the
      control of several physiological processes like growth, reproduction and
      digestion.

PMID- 10930561
TI  - Acute effects of bright light and caffeine on nighttime melatonin and temperature
      levels in women taking and not taking oral contraceptives.
AB  - Caffeine and bright light effects on nighttime melatonin and temperature levels
      in women were tested during the luteal phase of the menstrual cycle (n=30) or the
      pseudo luteal phase for oral contraceptive users (n=32). Participants were
      randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux)
      between 20:00 and 08:00 h under a modified constant routine protocol. Half the
      subjects in each lighting condition were administered either caffeine (100 mg) or
      placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results
      showed that the combination of bright light and caffeine enhanced nighttime
      temperature levels to a greater extent than did either caffeine or bright light
      alone. Both of the latter groups had higher temperature levels relative to the
      dim light placebo condition and the two groups did not differ. Temperature levels
      in the bright light caffeine condition were maintained at near peak circadian
      levels the entire night in the luteal and pseudo luteal phase. Melatonin levels
      were reduced throughout the duration of bright light exposure for all women.
      Caffeine reduced the onset of melatonin levels for women in the luteal phase, but
      it had little effect on melatonin levels for oral contraceptive users. The
      results for women in the luteal phase of the menstrual cycle are consistent with
      our previous findings in men. The results also suggest that oral contraceptives
      may alter the effects of caffeine on nighttime melatonin levels.

PMID- 10930562
TI  - Acute and chronic restraint stress: effects on [125I]-galanin binding in
      normotensive and hypertensive rat brain.
AB  - The neuropeptide galanin (GAL) has been implicated in the neural response to a
      number of stressors including restraint; however, the effect of restraint stress
      on GAL receptor density in the central nervous system (CNS) has not been
      investigated. Normotensive (Wistar-Kyoto; WKY) and hypertensive (spontaneously
      hypertensive; SHR) rats were subjected to a daily 60-min restraint stress
      paradigm for 0 (control), 1, 3, 5 or 10 consecutive days, and the density of
      [125I]-GAL binding sites following exposure to restraint was compared between
      strains using quantitative autoradiography. Significant differences in basal (no
      stress) levels of GAL receptor density between WKY and SHR were detected in
      regions such as the central nucleus of the amygdala (Ce) and ventromedial
      hypothalamus (VMH) (P<0.05). In WKY, restraint stress (1 day) induced significant
      decreases in GAL receptor density in forebrain regions such as the Ce (-41%) and
      medial nucleus of the amygdala (-41%) (P<0.05). Chronic restraint (10 days) did
      not induce significant decreases in these nuclei in WKY, indicating that
      forebrain neurons containing GAL receptors in WKY possessed a functional ability
      to adapt to repeated restraint. In addition, restraint stress induced significant
      decreases in GAL receptor density in SHR in regions such as the lateral
      parabrachial nucleus (-43%; 5 days of restraint) and hypoglossal nucleus (
      approximately -18% for entire restraint period) (P<0.05). In conclusion,
      restraint stress resulted in region- and strain-specific alterations in GAL
      receptor density, some of which may contribute to the altered stress response
      previously observed in hypertensive rats. The results clearly support the
      hypothesis that neuropeptides such as GAL are an integral component of the neural
      response to psychological stress, although the functional significance of the
      changes in GAL receptor density described in this study awaits elucidation.

PMID- 10930563
TI  - A Fourier-transform infrared study of the interaction between germ-cell specific
      sulfogalactosylglycerolipid and dimyristoylglycerophosphocholine.
AB  - In this study, we investigated structural and dynamic changes of
      sulfogalactosylglycerolipid (SGG) and dimyristoylglycerophosphocholine (DMPC) in
      a liposomal system (SGG+DMPC, molar ratio 2:3) by Fourier-transform infrared
      (FTIR) spectroscopy. Cooling of the preheated SGG liposomes (5-65 degrees C)
      revealed that the liquid crystalline-to-gel phase transition was centered at 45
      degrees C. SGG+DMPC liposomes showed a single phase transition at 28 degrees C.
      Spectral changes of the ester C&z. dbnd6;O groups of SGG and DMPC in the mixed
      liposomes indicated a decrease in their interfacial hydrogen bonding
      intermolecularly and with water. Analysis of SGG's symmetric and antisymmetric
      CH(2) stretching bands revealed that the insertion of DMPC into SGG bilayers
      increased the number of gauche conformers in SGG's hydrocarbon chains. Overall,
      the SGG+DMPC liposomes were homogeneous, with reduced interfacial hydrogen
      bonding and increased orientational and conformational disorder of SGG's
      hydrocarbon chains.

PMID- 10930564
TI  - Relating structure and translational dynamics in aqueous dispersions of
      monoolein.
AB  - The temperature dependence of the molecular diffusion in monoolein/water systems
      is investigated at several levels of hydration. Using the proton/deuteron
      selectivity, field gradient NMR allows the simultaneous determination of the
      diffusion constants of both, lipid and water molecules in the various lamellar
      and non-lamellar phases. Due to the mesoscopic structure of the monoolein/water
      phases, the diffusion coefficients are interpreted as 'reduced' or 'effective'
      diffusion coefficients, and are related to the microscopic molecular
      displacements by a so-called 'obstruction factor'. Changes in the microscopic
      structure at the phase transition from the bicontinuous cubic phases to the
      inverse hexagonal phase are reflected in the obstruction factor of the monoolein
      diffusion coefficients. The reduction of the water diffusion coefficients is too
      high to be explained by an obstruction factor only, implying a mechanism of
      molecular motion, which strongly differs from that of bulk water. Experiments on
      samples prepared with isotopic labeled water (2H(2)O and H(2)(17)O) indicate a
      chemical exchange of protons between the water molecules and the lipid headgroups
      on a millisecond timescale.

PMID- 10930565
TI  - Phase behavior of fully hydrated DMPC-amphiphilic cyclodextrin systems.
AB  - With the aim of exploring relationships between the chemical structure and the
      physico-chemical properties of amphiphilic beta-cyclodextrin, a reappraisal of
      the obtaining of pure heptakis (2,3-di-O-hexanoyl)-beta-cyclodextrin (beta
      CDC(6)) was undertaken. In this paper the chemical characterization of the newly
      synthesized beta-CDC(6) and its ability to form mixed structures with
      dimyristoylphosphatidylcholine (DMPC) are reported. Miscibility of the two
      amphiphiles is examined: (i) in monolayers formed at the air-water interface by
      analyzing the surface pressure-area isotherms; and (ii) in fully hydrated
      mixtures by differential scanning calorimetry (DSC) and X-ray diffraction at
      small and wide angles. Results demonstrate that the beta-cyclodextrin derivative
      is partially miscible to the phospholipid: intimate mixing occurs at beta-CDC(6)
      molar ratios smaller than 7-15 mol%, depending on the dimensional scale
      considered, while beyond these compositions phase separation is observed. At the
      air-water interface, the miscibility region of the two compounds shows non-ideal
      behavior characterized by the non-additivity of the molecular areas in the mixed
      monolayers. At the three-dimension level, the formation of a beta-CDC(6)/DMPC
      mixed lamellar phase occurs except at beta-CDC(6) molar ratios close to 5 mol% at
      which a highly ordered structure is depicted below the solid-to-liquid state
      transition of the DMPC hydrocarbon chains. At beta-CDC(6) contents higher than 7
      mol%, the mixed assemblies coexist with excess amphiphilic cyclodextrin which
      then forms a separated hexagonal structure.

PMID- 10930566
TI  - Lipid analysis of human spermatozoa and seminal plasma by MALDI-TOF mass
      spectrometry and NMR spectroscopy - effects of freezing and thawing.
AB  - In the present study, the applicability of proton NMR spectroscopy and matrix
      assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI
      TOF MS) to the analysis of the lipid composition of human spermatozoa and seminal
      fluids as well as changes after cryopreservation of human spermatozoa was
      investigated. Whereas NMR spectra primarily indicated a high content of double
      bonds within the spermatozoa but no marked differences upon cryopreservation, MS
      detected intense peaks which could be assigned to phosphatidylcholines containing
      one docosahexaenoic and one palmitic or stearic acid residue (m/z=806 and 834).
      In contrast, the seminal plasma contained more saturated fatty acids and
      especially more sphingomyelin (SM). A freezing/thawing cycle markedly influences
      the lipid composition of spermatozoa. There was a diminution of
      phosphatidylcholines (16:0, 22:6 and 18:0, 22:6) and SM (16:0) and the appearance
      of lysophosphatidylcholines (16:0 and 18:0) and ceramide (16:0). These data
      demonstrate the release or activation of both phospholipase A(2) and
      sphingomyelinase in human spermatozoa due to the freezing/thawing cycle. These
      results were finally confirmed by experiments on the action of phospholipases on
      lipids containing docosahexaenoic acid.

PMID- 10930567
TI  - Thermotropic and lyotropic properties of long chain alkyl glycopyranosides. Part
      II. Disaccharide headgroups.
AB  - We have investigated the thermotropic and lyotropic properties of some long chain
      alkyl glycosides with disaccharide headgroups. The thermotropism was measured
      with polarising microscopy and additionally the lyotropism with the contact
      preparation method, Fourier-transform Infrared (FTIR) spectroscopy, X-ray
      diffraction and small angle neutron scattering. A broad thermotropic as well as
      lyotropic polymorphism was found. The compounds displayed thermotropic S(A)
      (lamellar) and cubic phases, and the investigation of the lyotropic phase
      behaviour led to the observation of inverted bicontinuous cubic V(II) phases,
      lamellar L(alpha) phases, normal bicontinuous cubic V(I) phases, normal columnar
      H(I) phases, normal discontinuous cubic I(I) phases and lyotropic cholesteric
      phases. The phases are discussed with respect to the chemical structures that
      have been varied systematically to derive structure-property relationships.

PMID- 10930568
TI  - Dynamic light scattering of cutinase in AOT reverse micelles.
AB  - The fungal lipolytic enzyme cutinase, incorporated into sodium bis-(2ethylhexyl)
      sulfosuccinate reversed micelles has been investigated using dynamic light
      scattering. The reversed micelles form spontaneously when water is added to a
      solution of sodium bis-(2ethylhexyl) sulfosuccinate in isooctane. When an enzyme
      is previously dissolved in the water before its addition to the organic phase,
      the enzyme will be incorporated into the micelles. Enzyme encapsulation in
      reversed micelles can be advantageous namely to the conversion of water insoluble
      substrates and to carry out synthesis reactions. However protein unfolding occurs
      in several systems as for cutinase in sodium bis-(2ethylhexyl) sulfosuccinate
      reversed micelles. Dynamic light scattering measurements of sodium bis
      (2ethylhexyl) sulfosuccinate reversed micelles with and without cutinase were
      taken at different water to surfactant ratios. The results indicate that cutinase
      was attached to the micellar wall and that might cause cutinase unfolding. The
      interactions between cutinase and the bis-(2ethylhexyl) sulfosuccinate interface
      are probably the driving force for cutinase unfolding at room temperature. Twenty
      four hours after encapsulation, when cutinase is unfolded, a bimodal distribution
      was clearly observed. The radii of reversed micelles with unfolded cutinase were
      determined and found to be considerable larger than the radii of the empty
      reversed micelles. The majority of the reversed micelles were empty (90-96% of
      mass) and the remainder (4-10%) containing unfolded cutinase were larger by 26-89
      A.

PMID- 10930569
TI  - Simvastatin does not normalize very long chain fatty acids in
      adrenoleukodystrophy mice.
AB  - X-linked adrenoleukodystrophy (ALD) is a genetic demyelinating disorder
      characterized by accumulation of very long chain fatty acid (VLCFA) in tissues.
      Lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase,
      normalizes VLCFA in fibroblasts and plasma from ALD patients. We dietary treated
      ALD mice with simvastatin, an analog of lovastatin with similar pharmacokinetics
      and effects on plasma VLCFA in ALD patients at 20 or 60 mg/kg/day for 6-12 weeks.
      No decrease of VLCFA content was observed in mouse tissues, including the brain.
      A significant increase of VLCFA was rather observed in the brain of ALD mice at
      60 mg/kg/day.

PMID- 10930570
TI  - The mitogenic signaling pathway for fibroblast growth factor-2 involves the
      tyrosine phosphorylation of cyclin D2 in MCF-7 human breast cancer cells.
AB  - Fibroblast growth factor-2 (FGF-2) is mitogenic for the human breast cancer cell
      line MCF-7; here we investigate some of the signaling pathways subserving this
      activity. FGF-2 stimulation of MCF-7 cells resulted in a global increase of
      intracellular tyrosine phosphorylation of proteins, particularly FGF receptor
      substrate-2, the protooncogene product Src and the mitogen-activated protein
      kinase (MAP kinase) cascade. A major increase in the tyrosine phosphorylation of
      a 30-kDa protein species was also found. This protein was identified as cyclin D2
      by mass spectrometry after trypsin digestion. Immunoprecipitation of cyclin D2
      and immunoblotting with anti-phosphotyrosine antibodies confirmed that the
      tyrosine phosphorylation of cyclin D2 was indeed induced by FGF-2 stimulation. In
      addition, pharmacological inhibition of Src (with herbimycin A and PP2), and of
      the MAP kinase cascade (with PD98059), confirmed that Src activity is required
      for the FGF-2-induced phosphorylation of cyclin D2 whereas MAP kinase activity is
      not. Thus, tyrosine phosphorylation of cyclin D2 may be a key regulatory target
      for FGF-2 signaling.

PMID- 10930571
TI  - A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian
      family with faciogenital dysplasia (Aarskog-Scott syndrome).
AB  - Aarskog-Scott Syndrome (AAS) is an X-linked disorder characterised by short
      stature and multiple facial, limb and genital abnormalities. A gene, FGD1,
      altered in a patient with AAS phenotype, has been identified and found to encode
      a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac
      GEF). However, since this original report on identification of a mutated FGD1
      gene in an AAS patient, no additional mutations in the FGD1 gene have been
      described. We analysed 13 independent patients with clinical diagnosis of AAS.
      One patient presented a mutation that results in a nucleotide change in exon 10
      of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The
      mutation was found to segregate with the AAS phenotype in affected males and
      carrier females in the family of this patient. Interestingly, Arg-610 is located
      within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it
      corresponds to a highly conserved residue which has been involved in InsP binding
      in PH domains of other proteins. The same residue is often mutated in the
      Bruton's tyrosine kinase (Btk) gene in patients with an X-linked
      agammaglobulinemia. The Arg610Gln mutation represents the first case of a
      mutation in the PH domain of the FGD1 gene and additional evidence that mutations
      in PH domains can be associated to human diseases.

PMID- 10930572
TI  - Structural significance of the acyl group at the C-10 position and the A ring of
      the taxane core of paclitaxel for inducing nitric oxide and tumor necrosis factor
      production by murine macrophages.
AB  - The antitumor agent, paclitaxel (Taxol), mimics the actions of lipopolysaccharide
      (LPS) on murine macrophages (Mphi). Various synthetic analogs of paclitaxel were
      examined for their potencies to induce nitric oxide (NO) and tumor necrosis
      factor (TNF) production by murine peritoneal Mphi, and by human peripheral blood
      cells. The benzoyl group at C-2, the hydroxy group at C-7 and the acetyl group at
      C-10 were found to be critically important sites to activate murine Mphi. Nor
      seco-taxoid analogs lacking the A ring of the taxane core of paclitaxel were
      inactive, but inhibit paclitaxel- or LPS-induced NO production. All the compounds
      tested did not induce TNF production by human blood cells.

PMID- 10930573
TI  - Possible His to Asp phosphorelay signaling in an Arabidopsis two-component
      system.
AB  - We have so far cloned a cDNA encoding a hybrid-type histidine kinase (ATHK1),
      three cDNAs encoding phosphorelay intermediates (ATHP1-3), and four cDNAs
      encoding response regulators (ATRR1-4) from Arabidopsis thaliana. To determine
      which molecules constitute a His to Asp phosphorelay pathway, we examined protein
      protein interactions between them using a pairwise yeast two-hybrid analysis, as
      an initial step. We detected a specific interaction between ATHK1 and ATHP1. We
      further examined protein-protein interactions between ATHP1-3 and other histidine
      kinases. We detected interactions between ETR1 and all ATHPs, and between CKI1
      and ATHP1 or ATHP2. Interestingly, ERS1 could not interact with any ATHPs. We
      also examined protein-protein interactions between ATHP1-3 and ATRR1-4. The
      results indicated that ATHP2 could interact with ATRR4, and that ATHP3 could
      interact with ATRR1 or ATRR4. However, ATHP1 could not interact with any ATRRs.
      On the basis of these results, we discuss the possible phosphorelay networks in
      an Arabidopsis two-component system.

PMID- 10930574
TI  - Selective phosphotyrosine phosphatase inhibition and increased ceramide formation
      is associated with B-cell death by apoptosis.
AB  - Bis(maltolato)oxovanadium(IV) (BMOV), a protein phosphotyrosine phosphatase
      inhibitor, selectively induced apoptosis (as quantitated by TUNEL staining) in a
      B-cell line (Ramos) but not in a T-cell line (Jurkat). The pattern of BMOV
      induced protein tyrosine phosphorylation was different in B-cells versus T-cells.
      Further, BMOV induced a 2-fold increase in ceramide levels in B-cells but not in
      T-cells and this resembled the ceramide increase following activation of the B
      cell antigen receptor. A 2-fold increase in the ratio of ceramide to
      sphingomyelin in B-cells treated with BMOV suggested that sphingomyelinase
      activation was the result of the sustained tyrosine phosphorylation of specific
      proteins and activated the cell death pathway.

PMID- 10930575
TI  - The role of mitochondrial dysfunction in regulation of store-operated calcium
      channels in glioma C6 and human fibroblast cells.
AB  - The store-operated calcium influx into electrically non-excitable cells is
      greatly modified under the condition of deenergized mitochondria in situ. The
      rate of calcium influx into cells with empty intracellular calcium stores is
      greatly diminished when cells were pretreated with 2 microM carbonyl cyanide m
      chlorophenylhydrazone (a mitochondrial uncoupler) or with 4 microM myxothiazol
      (an inhibitor of the respiratory chain). We demonstrate that this general
      phenomenon takes place in the case of transformed (glioma C6 and Ehrlich ascites
      tumor cells) as well as non-transformed (human fibroblasts) cells. We also
      demonstrate that the deenergization of mitochondria affects the cellular calcium
      influx rate and not the calcium pump on the plasma membrane.

PMID- 10930576
TI  - ADAMTS-1 cleaves a cartilage proteoglycan, aggrecan.
AB  - A disintegrin-like and metalloproteinase with thrombospondin type I motifs-1
      (ADAMTS-1) is an extracellular matrix-anchored metalloproteinase. In this study
      we have demonstrated that ADAMTS-1 is able to cleave a major cartilage
      proteoglycan, aggrecan. N-terminal sequencing analysis of the cleavage product
      revealed that ADAMTS-1 cleaves the Glu(1871)-Leu(1872) bond within the
      chondroitin sulfate attachment domain of aggrecan. In addition, deletional
      analysis demonstrated that the C-terminal spacer region of ADAMTS-1 is necessary
      to degrade aggrecan. These results suggest that ADAMTS-1 may be involved in the
      turnover of aggrecan in vivo.

PMID- 10930577
TI  - Effects of mutation at a conserved N-glycosylation site in the bovine retinal
      cyclic nucleotide-gated ion channel.
AB  - Bovine retinal cyclic nucleotide-gated (CNG) ion channel contains an evolutionary
      conserved N-glycosylation site in the external loop between the fifth
      transmembrane segment and the pore-forming region. The effect of tunicamycin
      treatment and the site-specific mutation suggested that the channel is
      glycosylated when expressed in Xenopus oocytes. To test the role of glycosylation
      in this channel, N-glycosylation was abolished by mutation, and the detailed
      permeation and the gating characteristics of the mutant channel were
      investigated. The charge contribution turned out to be detectable, although the
      mutation of the N-glycosylation site did not affect expression and functionality
      of the CNG channel in oocytes.

PMID- 10930578
TI  - PKB/Akt interacts with inosine-5' monophosphate dehydrogenase through its
      pleckstrin homology domain.
AB  - The pleckstrin homology (PH) domain of the protooncogenic serine/threonine
      protein kinase PKB/Akt can bind phosphoinositides. A yeast-based two-hybrid
      system was employed which identified inosine-5' monophosphate dehydrogenase
      (IMPDH) type II as specifically interacting with PKB/Akts PH domain. IMPDH
      catalyzes the rate-limiting step of de novo guanosine-triphosphate (GTP)
      biosynthesis. Using purified fusion proteins, PKB/Akts PH domain and IMPDH
      associated in vitro and this association moderately activated IMPDH. Purified
      PKB/Akt also associated with IMPDH in vitro. We could specifically pull-down
      PKB/Akt or IMPDH from mammalian cell lysates using glutathione-S-transferase
      (GST)-IMPDH or GST-PH domain fusion proteins, respectively. Additionally, PKB/Akt
      and IMPDH could be co-immunoprecipitated from COS cell lysates and active PKB/Akt
      could phosphorylate IMPDH in vitro. These results implicate PKB/Akt in the
      regulation of GTP biosynthesis through its interaction with IMPDH, which is
      involved in providing the GTP pool used by signal transducing G-proteins.

PMID- 10930579
TI  - Acid sphingomyelinase is involved in CEACAM receptor-mediated phagocytosis of
      Neisseria gonorrhoeae.
AB  - The interaction with human phagocytes is a hallmark of symptomatic Neisseria
      gonorrhoeae infections. Gonococcal outer membrane proteins of the Opa family
      induce the opsonin-independent uptake of the bacteria that relies on CEACAM
      receptors and an active signaling machinery of the phagocyte. Here, we show that
      CEACAM receptor-mediated phagocytosis of Opa(52)-expressing N. gonorrhoeae into
      human cells results in a rapid activation of the acid sphingomyelinase.
      Inhibition of this enzyme by imipramine or SR33557 abolishes opsonin-independent
      internalization without affecting bacterial adherence. Reconstitution of
      ceramide, the product of acid sphingomyelinase activity, in imipramine- or
      SR33557-treated cells restores internalization of the bacteria. Furthermore, we
      demonstrate that CEACAM receptor-initiated stimulation of other signalling
      molecules, in particular Src-like tyrosine kinases and Jun N-terminal kinases,
      requires acid sphingomyelinase. These studies provide evidence for a crucial role
      of the acid sphingomyelinase for CEACAM receptor-initiated signalling events and
      internalization of Opa(52)-expressing N. gonorrhoeae into human neutrophils.

PMID- 10930580
TI  - The human homologue of the yeast mitochondrial AAA metalloprotease Yme1p
      complements a yeast yme1 disruptant.
AB  - In yeast, three AAA superfamily metalloproteases (Yme1p, Afg3p and Rca1p) are
      localized to the mitochondrial inner membrane where they perform roles in the
      assembly and turnover of the respiratory chain complexes. We have investigated
      the function of the proposed human orthologue of yeast Yme1p, encoded by the
      YME1L gene on chromosome 10p. Transfection of both HEK-293EBNA and yeast cells
      with a green fluorescent protein-tagged YME1L cDNA confirmed mitochondrial
      targeting. When expressed in a yme1 disruptant yeast strain, YME1L restored
      growth on glycerol at 37 degrees C. We propose that YME1L plays a
      phylogenetically conserved role in mitochondrial protein metabolism and could be
      involved in mitochondrial pathologies.

PMID- 10930581
TI  - Evidence for an active role of the DnaK chaperone system in the degradation of
      sigma(32).
AB  - Under non-stressed conditions in Escherichia coli, the heat shock transcription
      factor sigma(32) is rapidly degraded by the AAA protease FtsH. The DnaK chaperone
      system is also required for the rapid turnover of sigma(32) in the cell. It has
      been hypothesized that the DnaK chaperone system facilitates the degradation of
      sigma(32) by sequestering it from RNA polymerase core. This hypothesis predicts
      that mutant sigma(32) proteins, which are deficient in binding to RNA polymerase
      core, will be degraded independently of the DnaK chaperone system. We examined
      the in vivo stability of such mutant sigma(32) proteins. Results indicated that
      the mutant sigma(32) proteins as similar as authentic sigma(32) were stabilized
      in DeltadnaK and DeltadnaJ/DeltacbpA cells. The interaction between sigma(32) and
      DnaK/DnaJ/GrpE was not affected by these mutations. These results strongly
      suggest that the degradation of sigma(32) requires an unidentified active role of
      the DnaK chaperone system.

PMID- 10930582
TI  - Incorporation of N-propanoylneuraminic acid leads to calcium oscillations in
      oligodendrocytes upon the application of GABA.
AB  - Sialylation of glycoproteins and glycolipids plays an important role during
      development, regeneration and pathogenesis. It has been shown that unnatural
      sialylation within glial cell cultures can have distinct effects on their
      proliferation and antigenic profiles. These cultures metabolize N
      propanoylmannosamine (N-propanoylneuraminic acid precursor=P-NAP), a synthetic
      non-physiological precursor of neuraminic acid, resulting in the expression of N
      propanoylneuraminic acid in glycoconjugates of their cell membranes [Schmidt, C.,
      Stehling, P., Schnitzer, J., Reutter, W. and Horstkorte, R. (1998) J. Biol. Chem.
      273, 19146-19152]. To determine whether these biochemically engineered sialic
      acids influence calcium concentrations in cells of the oligodendrocyte lineage,
      mixed glial cultures of oligodendrocytes growing on top of an astrocyte monolayer
      were exposed to glutamate, histamine, adrenaline, gamma-aminobutyric acid (GABA),
      high potassium (high K(+)) and ATP. Calcium responses in P-NAP-treated
      oligodendrocytes were determined by confocal microscopy with the calcium
      indicator fluo-3 AM, and compared with control cultures. We showed that P-NAP
      differentially modulated the calcium responses of individual oligodendrocytes
      when GABA was applied. GABA induced calcium oscillations with up to four spikes
      per min in 60% of oligodendrocytes when treated with P-NAP.

PMID- 10930584
TI  - Changes in intramitochondrial cardiolipin distribution in apoptosis-resistant HCW
      2 cells, derived from the human promyelocytic leukemia HL-60.
AB  - Using a cytofluorimetric approach, we studied intramitochondrial cardiolipin (CL)
      distribution in HCW-2 cells, an apoptosis-resistant clone of human HL-60 cells.
      In HL-60, about 50% of total CL is distributed in the outer leaflet of
      mitochondrial inner membrane, while in HCW-2 a significantly higher amount of CL
      (about 65%) is in that site. In basal conditions, HSW-2 cells also show a reduced
      mitochondrial membrane potential even if they are able to proliferate as the
      parental line. Taking into account the complex functions that CL plays in the
      regulation of mitochondrial activity, it is likely that HCW-2 could produce ATP
      utilizing more glycolytic pathways rather than mitochondrial respiratory chain.

PMID- 10930583
TI  - Production of polyomavirus structural protein VP1 in yeast cells and its
      interaction with cell structures.
AB  - The gene for mouse polyomavirus major structural protein VP1 was expressed in
      Saccharomyces cerevisiae from the inducible GAL7 promoter. VP1 pseudocapsids were
      purified from cell lysates. Their subpopulation contained fragments of host DNA,
      which, in contrast to those of VP1 pseudocapsids produced in insect cells, did
      not assemble with cellular histones into pseudonucleocores. VP1 pseudocapsids
      accumulated in the yeast cell nuclei. A strong interaction of VP1 with tubulin
      fibres of the mitotic spindle was observed. The fibres of spindles were larger in
      diameter, apparently due to tight VP1 binding. Substantial growth inhibition of
      yeast cells producing VP1 was observed.

PMID- 10930585
TI  - Zeta-crystallin catalyzes the reductive activation of 2,4,6-trinitrotoluene to
      generate reactive oxygen species: a proposed mechanism for the induction of
      cataracts.
AB  - Exposure to 2,4,6-trinitrotoluene (TNT) has been shown to cause induction of
      cataract in which oxidative stress plays a critical role. From bovine lens we
      purified to homogeneity and identified an enzyme that catalyzes the reduction of
      TNT, resulting in the production of reactive oxygen species. The final
      preparation of TNT reductase showed a single band with a subunit molecular weight
      of 38 kDa on SDS-PAGE. Sequence data from peptides obtained by digestion with
      lysylendopeptidase Achromobacter protease I (API) revealed that TNT reductase is
      identical to zeta-crystallin. Superoxide anions were formed during reduction of
      TNT by zeta-crystallin, though negligible enzyme activity or protein content for
      superoxide dismutase, a superoxide scavenging enzyme, was found in the lens.
      Thus, the present results suggest that the induction of cataracts by TNT may be
      associated with increased oxidative stress, as a result of reductive activation
      of TNT generating superoxide anions, there being minimal antioxidant enzyme
      activity for defense against reactive oxygen species exogenously produced in the
      lens.

PMID- 10930586
TI  - A putative binding protein for lipophilic substances related to butterfly
      oviposition.
AB  - A unique protein of 23 kDa (Jf23) was found in the tarsus of the female
      swallowtail butterfly, Atrophaneura alcinous. Jf23 has 38% identity with a bilin
      binding protein, which was found in the cabbage butterfly, Pieris brassicae, and
      which has two consensus sequences in common with the members of the lipocalin
      family, suggesting that it is a binding protein for lipophilic ligands. Western
      blot analysis showed that Jf23 was expressed only in the female, and not in the
      male. Electrophysiological response of the female tarsi was stimulated by
      methanolic extract of their host plant, Dutchman's pipe (Aristolochia debilis).
      The stimulated response was depressed by the presence of Jf23 antiserum. These
      results suggest that Jf23 is one of the chemosensory signaling proteins, which
      plays one or more roles in female butterfly oviposition.

PMID- 10930587
TI  - Calcium signaling in lymphocytes and ELF fields: evidence for an electric field
      metric and a site of interaction involving the calcium ion channel.

PMID- 10930588
TI  - Prognostic factors in artificially ventilated stroke patients.
AB  - OBJECTIVES: To evaluate the reasons for implementing artificial ventilation (AV)
      in patients with acute ischemic stroke (AIS), determine their outcome and
      characterize prognostic variables in these patients. METHODS: Consecutive
      patients presenting with AIS were evaluated. All patients who received AV were
      treated in a neurological semi-intensive care setting. RESULTS: Of the 173
      patients included in the study, 27 (16%) needed AV, 16 (9%) received AV and five
      of these patients (31%) survived. The mean NIH stroke scale score prior to AV was
      14.5+/-5.6 (vs. 9.1+/-6.2 in non-intubated patients, P=0.001). Six patients were
      ventilated because of neurological deterioration. Most of these patients had
      large hemispheric infarctions with evident herniation and midline shift on CT
      scans. The only one who survived the acute hospitalization did not recover and
      died within 3 months. In the other 10 patients, AV was instituted during
      cardiopulmonary decompensation (CPD). These patients generally fared better; four
      of them survived and were discharged after a lengthier hospital stay when
      compared to non-intubated patients. Variables associated with survival among
      intubated patients were a lower neurological disability score on admission and on
      day 7 after the stroke, and intubation during CPD. CONCLUSIONS: Implementing AV
      in semi-intensive care settings does not seem to improve survival in AIS patients
      with neurological deterioration. Stroke patients who need AV during CPD and those
      that have less severe neurological deficits may have better chances for survival.

PMID- 10930589
TI  - Increased reactive oxygen species in familial amyotrophic lateral sclerosis with
      mutations in SOD1.
AB  - Amyotrophic lateral sclerosis (ALS) is a paralytic disorder characterized by
      degeneration of large motor neurons of the brain and spinal cord. A subset of ALS
      is inherited (familial ALS, FALS) and is associated with more than 70 different
      mutations in the SOD1 gene. Here we report that lymphoblast cell lines derived
      from FALS patients with 16 different mutations in SOD1 gene exhibit significant
      increase of intracellular reactive oxygen species (ROS) compared with sporadic
      ALS (SALS) and normal controls (spouses of ALS patients). The ROS generation did
      not correlate with SOD1 activity. Further, cells incubated with vitamin C,
      catalase or the flavinoid quercetin significantly reduced ROS in all groups. The
      catalase inhibitor 3-amino-1,2,4-triazole resulted in a ten-fold increase of ROS
      in all groups. Neither L-nitroarginine, a nitric oxide synthase inhibitor or
      vitamin E altered the ROS levels. Thus, these studies suggest that hydrogen
      peroxide (H(2)O(2)) is a major ROS elevated in FALS lymphoblasts and it may
      contribute to the degeneration of susceptible cells. Further, we postulate a
      mechanism by which increased H(2)O(2) could be generated by mutant SOD1.

PMID- 10930590
TI  - Axonal damage revealed by accumulation of beta-amyloid precursor protein in HTLV
      I-associated myelopathy.
AB  - We investigated the localization and extent of beta-amyloid precursor protein
      (APP) immunoreactivity as a sensitive marker for impairment of fast axonal
      transport in the spinal cords of patients with HTLV-I-associated myelopathy
      (HAM)/tropical spastic paraparesis (TSP). The results from this study show that
      APP, used as a marker of early axonal damage in HAM/TSP lesions, is more
      intensively expressed in areas of active-inflammatory lesions than those of
      inactive-chronic lesions. The close localization to the areas containing
      inflammation (activation of macrophage/microglia) is striking and suggests that
      axonal damage is closely associated with inflammation in active-chronic lesions.
      Although inflammatory cell infiltration in the central nervous system (CNS) is
      rarely found in inactive-chronic lesions, a few clusters of APP+ axons are found
      in the spinal cord white matter in some cases. The presence of APP+ axons without
      relation to inflammatory cells in inactive-chronic lesions, suggest that soluble
      neurotoxic factors might induce axonal changes in the CNS of HAM/TSP. The
      occasional myelinated fibers in the anterior and posterior spinal roots in lower
      thoracic to lumbar levels had APP+ axons, suggesting that spinal nerve roots can
      be affected in HAM/TSP, especially in lower thoracic to lumbar levels. Impairment
      of fast axonal transport may contribute to the development of disability in
      patients with HAM/TSP.

PMID- 10930591
TI  - Regional differences in cerebral blood flow during recitation of the
      multiplication table and actual calculation: a positron emission tomography
      study.
AB  - Regional cerebral differences in activation by two types of calculation,
      quantitative number processing and use of rote verbal arithmetic memory, were
      investigated. METHODS: The two types of processing were induced by serial number
      subtraction (the Subtra-task) and recitation of the multiplication table (the
      Multi-task), respectively. Regional cerebral blood flow (rCBF) under the two
      tasks was measured in ten healthy right-handed Japanese men using (15)O-labeled
      water and positron emission tomography (PET). Statistical parametric mapping
      (SPM) was used for estimating rCBF differences during these tasks. RESULTS: The
      activated areas during the Subtra-task were consistent with those reported to be
      involved in quantitative number processing. Although most of the regions
      activated during the Multi-task were in common with the regions activated during
      the Subtra-task, the spatial extent of the activation during the Multi-task was
      smaller. Moreover, the left lenticular nucleus was activated during the Multi
      task, but not in the Subtra-task, while the prefrontal cortex was activated in
      the Subtra-task but not in the Multi-task. CONCLUSION: The difference in the
      regions activated by the two tasks, and the difference in the spatial extent of
      each region by the two tasks indicated that the anatomical networks of the two
      processes were segregated.

PMID- 10930592
TI  - Basophilic cytoplasmic inclusions in a case of sporadic juvenile amyotrophic
      lateral sclerosis.
AB  - A 24-year-old woman presented with progressive muscle atrophy and weakness of the
      right upper extremity. Subsequently her weakness rapidly extended to the left
      upper extremity, neck and lower extremities. Neurological examination disclosed
      involvement of the lower motor neuron system. She died 7 months after the onset.
      There was neuronal loss and reactive gliosis in the anterior horns of the spinal
      cord and much less frequently in the motor cortex. Basophilic cytoplasmic
      inclusions were observed in the thalamus and brain stem as well as the upper and
      lower motor neurons. Ultrastructurally, the inclusions lacked a limiting membrane
      and consisted of a meshwork of filamentous structures associated with granules.
      The inclusions failed to react with antibodies against phosphorylated
      neurofilament or cystatin C. Most of the inclusions show no reaction with anti
      ubiquitin antibody, however, a few inclusions show granular reaction product
      deposits with this antibody. The inclusions were not immunostained with
      antibodies against TGN46 and MG-160, markers of the trans-Golgi network and the
      medial cisternae of the Golgi apparatus, respectively, suggesting that they were
      not derived from the Golgi apparatus which was fragmented.

PMID- 10930593
TI  - Effects of single and repetitive spreading depression on cerebral blood flow and
      glucose metabolism in cats: a PET study.
AB  - To clarify the effects of spreading depression (SD) on cerebral circulation and
      metabolism, we elicited a single or repetitive episode of SD and evaluated CBF
      and CMRglc three-dimensionally in normal cats (n=4, in each group) using a high
      resolution positron emission tomography (PET) scanner. SD was evoked by applying
      KCl to the left occipital cortex. We then monitored DC potential changes with
      tungsten electrodes inserted into the left temporal cortex. CBF was measured
      twice before and three times (immediately, 30-60 min, and 60-120 min) following
      KCl application using [15O]H(2)O, and CMRglc was determined using 2-[18F]fluoro-2
      deoxy-D-glucose immediately following the last CBF measurement. The following
      results were obtained: (1) a single episode of SD produced a temporary CBF
      increase, followed by a long-lasting hypoperfusion in the cortex, with no
      significant changes to CBF observed in the subcortex; (2) no significant CMRglc
      changes were observed in either cortical or subcortical regions following a
      single episode of SD; (3) a flow-metabolism uncoupling was observed in the
      cortical regions concurrently with persistent hypoperfusion; (4) repetitive SD
      produced significant CBF changes in the cortex; and (5) the cortical CMRglc
      increased as a result of repeated episodes of SD, with no significant changes
      observed in the subcortex. Thus, we succeeded in determining three-dimensionally
      the effects of single and repetitive SD on CBF and CMRglc in cats using a high
      resolution PET scanner. The present study provides the first direct evidence of
      CBF-CMRglc uncoupling occurring concurrently with persistent hypoperfusion
      following SD.

PMID- 10930594
TI  - Association of L-DOPA with recovery following Ayurveda medication in Parkinson's
      disease.
AB  - Ayurveda, the Indian system of traditional medicine, uses a concoction of several
      spices, herbs and minerals for the treatment of diseases. In a clinical
      prospective study we have evaluated the efficacy of Ayurveda treatment (a
      concoction in cow's milk of powdered Mucuna pruriens and Hyoscyamus reticulatus
      seeds and Withania somnifera and Sida cordifolia roots) in 18 clinically
      diagnosed (with a mean Hoen and Yahr value of 2.22) parkinsonian patients. As per
      Ayurveda principles, 13 patients underwent both cleansing (for 28 days) and
      palliative therapy (56 days), 5 patients underwent palliative therapy alone (84
      days). Only the former group showed significant improvement in activities of
      daily living (ADL) and on motor examination as per UPDRS rating. Symptomatically,
      they exhibited better response in tremor, bradykinesia, stiffness and cramps as
      compared to the latter group. Excessive salivation worsened in both the groups.
      Analyses of powdered samples in milk, as administered in patients, revealed about
      200 mg of L-DOPA per dose. The study establishes the necessity of cleansing
      therapy in Ayurveda medication prior to palliative therapy. It also reveals
      contribution of L-DOPA in the recovery as observed in Parkinson' disease
      following Ayurveda medication.

PMID- 10930595
TI  - Cervical cord magnetic resonance imaging findings in systemic immune-mediated
      diseases.
AB  - Brain magnetic resonance imaging (MRI) findings in patients with systemic immune
      mediated diseases (SID) affecting the central nervous system (CNS) are
      heterogeneous and lack diagnostic specificity. In the present study, we evaluated
      the potential role of cervical cord MRI for increasing confidence when making a
      diagnosis of SID. Sagittal, T2-weighted images of the cervical cord were obtained
      in patients affected by systemic lupus erythematosus (SLE) with (NSLE, n=9) and
      without clinical CNS involvement (n=15), Behcet disease (BD, n=5), Wegener
      granulomatosis (WG, n=9), antiphospholipid antibody syndrome (APLAS, n=6) and
      multiple sclerosis (MS, n=10). Spinal cord hyperintense lesions were found in
      9/10 MS patients, while no lesions were visible in the cervical cord of any
      patient with SID, regardless of the presence or absence of brain abnormalities.
      Cervical cord MRI can be useful in diagnosing patients suspected of having a SID.

PMID- 10930596
TI  - Risk of seizures and neurocysticercosis in household family contacts of children
      with single enhancing lesions.
AB  - A small, single enhancing lesion (SEL) is often noted upon computed tomography
      (CT) in children and young adults with recent focal or generalized seizures. A
      high frequency of seizures has been reported in family members of persons with
      SEL. We studied the prevalence of seizures and cysticercus electro-immuno
      transfer blot (EITB) based seropositivity among family members, specifically
      household family contacts of pediatric subjects with a SEL. An attempt was also
      made to determine the etiology of seizures in household family contacts using
      magnetic resonance imaging (MRI). Information regarding seizure semiology,
      personal and food habits and detailed family pedigrees was obtained from 20
      consecutive pediatric subjects with a SEL and 51 of their household family
      contacts. EITB sero-assays and stool examinations were performed on all
      participating subjects. MRIs were done on all EITB positive household family
      contacts. A family history of seizures was obtained in six index children (30%)
      (five household first-degree relatives and two distant relatives). Seventeen
      index children (85%) and 14 family contacts (27%) were EITB positive. A tendency
      towards clustering of EITB positive cases within individual families was
      observed. Stool examinations did not reveal Taenia species ova in any of EITB
      positive subjects. Neuroimaging studies revealed abnormalities consistent with
      active or inactive neurocysticercosis in all five household family contacts with
      history of seizures. Four of these five subjects were EITB positive and one was
      EITB negative. We concluded that children with SEL and seizures may have a family
      history of seizures. There is a high seropositivity rate in household family
      contacts of pediatric subjects with solitary cysticercus granulomas (SCGs). EITB
      based seropositivity in household family contacts with seizures, strongly
      predicts a cysticercal etiology for seizures. It may be worthwhile to screen
      household family contacts of children with SEL for taeniasis-cysticercosis.

PMID- 10930597
TI  - Attentional modulation of parieto-occipital cortical responses: implications for
      hemispatial neglect.
AB  - Functional magnetic resonance imaging (fMRI) was used to examine whether
      preattentive and attentive visual processing, the cognitive psychological
      dichotomy on normal vision, indeed activate the parieto-occipital systems
      differentially as suggested by recent neuropsychological research. The activation
      paradigms consisted of feature detection and discrimination of line orientation,
      and visual fixation, which corresponded to preattentive, attention-requiring, and
      baseline conditions, respectively. The detection versus fixation contrast
      revealed activation sites in the right lateral prefrontal cortex and bilateral
      occipital lobes, whereas the discrimination versus fixation contrast showed
      broader bilateral activations extending from the occipital lobes through the
      parietal lobes, prefrontal cortex, thalamus, basal ganglia and upper brainstem.
      In the discrimination versus detection contrast, significant activations were
      observed in the right superior and inferior parietal lobules as well as in the
      subcortical structures. These findings were consistently demonstrated both at
      intra- and inter-subject levels. The present study provides further evidence to
      delineate neural substrate for the two distinct modes of visual processing and
      helps us to understand the neuropsychological mechanism underlying visual
      attention disorders.

PMID- 10930598
TI  - Anti-sulfatide IgM antibodies in peripheral neuropathy.
AB  - Anti-sulfatide IgM antibodies have been recently associated with neuropathy but
      the clinical and electrophysiological correlations of this reactivity remains
      unclear. We reviewed the clinical and electrophysiological features of patients
      with high anti-sulfatide titers detected in our laboratory from 1991 to 1998. Of
      the 564 patients with different neurological diagnosis tested by enzyme-linked
      immunosorbent assay (ELISA), 11 had high anti-sulfatide IgM titers (>1/8000), 26
      had titers of 1/8000 while 78 had titers of 1/4000. All patients with high anti
      sulfatide IgM titers had a chronic, dysimmune, mostly sensorimotor neuropathy
      that in seven was associated with IgM monoclonal gammopathy. In most of these
      patients electrophysiological and morphological studies were consistent with a
      predominantly demyelinating neuropathy frequently associated with prominent
      axonal loss. Antibody titers of 1/8000, though always associated with neuropathy,
      did not correlate with a particular form or cause of neuropathy, while lower
      titers were equally distributed in patients with different neurological
      disorders. Our study indicate that high anti-sulfatide IgM titers (>1/8000) are
      highly predictive for a chronic, dysimmune, mostly demyelinating neuropathy often
      associated with IgM monoclonal gammopathy, and may therefore have potential
      diagnostic relevance.

PMID- 10930599
TI  - A novel mutation of the McLeod syndrome gene in a Japanese family.
AB  - McLeod syndrome is a rare X-linked hematologic and neuromuscular disorder
      manifested by chorea, myopathy, cardiomyopathy, areflexia, hyperCKemia, and
      acanthocytosis. Only four mutations have been reported in the gene responsible
      for McLeod syndrome. We report a novel gene mutation in a Japanese family. Direct
      sequencing of the PCR-amplified genomic DNA revealed the mutation was a single C
      nucleotide insertion at codon 151 in exon 2 of the XK gene, which resulted in a
      3'-frameshift. Study of family members revealed that the patient's mother was a
      manifesting carrier heterozygous for this mutation.

PMID- 10930600
TI  - Infarct presenting with a combination of Wallenberg and posterior spinal artery
      syndromes.
AB  - This is the first report of a patient presenting with a combination of Wallenberg
      and posterior spinal artery syndromes. The patient developed right hemiplegia and
      sensory disturbances on the right side of the face and over the whole body. MRI
      showed infarcts of the cerebellum, medulla oblongata, and upper cervical cord.
      These lesions were in the territory of the right posterior inferior cerebellar
      artery (PICA) and the right posterior spinal artery (PSA). The combination was
      due to severe stenosis of the right vertebral artery.

PMID- 10930601
TI  - Sjogren's syndrome with acute transverse myelopathy as the initial manifestation.
AB  - This is the first report of a patient with acute transverse myelopathy as the
      initial manifestation of primary Sjogren's syndrome (SS). The patient developed
      tetraparesis and sensory disturbance within 6 days of onset. Spinal MRI showed an
      extensive intraparenchymal lesion with high T2-weighted signal intensity,
      gadolinium enhancement, and cord swelling. Although the patient did not show
      clinical sicca symptoms, primary SS was diagnosed on the basis of clinical tests
      on lacrimal and salivary glands which showed high levels of autoantibodies.
      Treatment with prednisone improved motor and sensory symptoms and resulted in
      improvement of MRI findings. The present case suggests that acute transverse
      myelopathy can occur as an initial symptom of SS.

PMID- 10930602
TI  - Autosomal dominant temporal lobe epilepsy in a Japanese family.
AB  - We described autosomal dominant familial temporal lobe epilepsy in a Japanese
      family in which three individuals (one man and his two children) were affected.
      Their seizures commonly consisted of auditory symptoms and infrequent nocturnal
      generalized seizures. Repeated EEGs did not provide confirmative epileptiform
      discharges, but cranial MRI in one patient showed mild left hippocampal atrophy,
      and decreased glucose metabolism in the left temporal area was demonstrated by
      18F-deoxyglucose positron emission tomography (FDG-PET). A confirmative diagnosis
      in one of the patients by FDG-PET was helpful for diagnosis in other patients in
      the same family. Seizure onset was adolescent commonly among the three patients,
      but better seizure control was achieved in the father as compared with the two
      children.

PMID- 10930603
TI  - Monocotyledon fruits and seeds, and an associated palynoflora from Eocene
      Oligocene sediments of coastal central Queensland, Australia.
AB  - Fruits of Restionaceae and seeds of Typhaceae are described from a latest Eocene
      Oligocene mudstone underlying oil shales in a subsurface sequence near
      Rockhampton, coastal central Queensland. The Restionaceae fruits are unilocular
      and encase a single pendulous orthotropous seed with a structured micropylar cap,
      which may be tannin filled. These are allocated to Restiocarpum gen. nov., which
      has as its type Restiocarpum latericum sp. nov., and four other taxa described
      herein; Restiocarpum tesselatum sp. nov., Restiocarpum verrucatum sp. nov.,
      Restiocarpum laeve sp. nov., and Restiocarpum fusiforme sp. nov. Typhaspermum
      cooksoniae gen. et sp. nov., which accommodates asymmetric claviform seeds, is
      interpreted as a member of the Typhaceae based on the presence of a lid-like
      operculum, bitegmic wall, and chalazal cavity.Reconstruction of the source plant
      community emphasizes similarities to restiad swamps of present day Wallum (swamp
      heathland) vegetation which is extensively developed along the Queensland coast.
      Biogeographic implications for the Restionaceae and Typhaceae are discussed.

PMID- 10930604
TI  - A new species of Discinites (Noeggerathiales) from the Upper Permian of Weibei
      Coalfield, North China.
AB  - A new species of Discinites is described from the Late Permian Upper Shihhotse
      Formation of the Weibei Coalfield, Shaanxi Province, China. D. hanchengensis sp.
      nov. has decurrent and disk-like sporophylls with deep-toothed apices, elliptical
      sporangia and rectangular epidermal cells. The spores are generally of the
      Calamospora type. The megaspores and microspores are 300-380 and 45-90um in
      diameter, respectively. The microspores are similar in size to those of all other
      species of Discinites that contain Calamospora, but the megaspores are remarkably
      smaller. The new species represents the first record of Discinites with
      Calamospora from China and from the Cathaysian flora. Finally, we summarize the
      associated foliages of Discinites in the Cathaysian flora and find that they are
      all markedly different from those found in the Euramerican flora.

PMID- 10930605
TI  - Pollen-rain-vegetation relationships along a forest-savanna transect in
      southeastern Cameroon.
AB  - Modern soil and litter samples from southeastern Cameroon, collected along a
      continuous forest-savanna transect were analysed for pollen content to define
      modern pollen-vegetation relationships. The pollen results, completed and
      compared with botanical inventories, leaf area index and basal area measurements
      performed in the same area, clearly registered the physiognomy, the main
      floristic composition and floral richness of the two sampled ecosystems.
      Distortions were observed between sampled vegetations and their pollen rain,
      related to important differences in pollen production and dispersal of plant
      species: this is a general feature in many tropical regions. The pollen data in
      the area studied reflected well the recent transgression of forest versus
      savanna. This permitted us to define inside the forest ecosystem more
      successional vegetation communities than the botanical surveys allowed.

PMID- 10930606
TI  - Megaspores from the Late Permian, Lower Whybrow coal seam, Sydney Basin,
      Australia.
AB  - More than 300 megaspore specimens have been recovered from samples from the Late
      Permian, Lower Whybrow coal seam of the Wittingham Coal Measures of the Sydney
      Basin. Only two species are recognised: Singhisporites surangei (Singh) Potonie,
      emend. and a new species of Singhisporites. Species distribution within the seam
      is controlled by a major fire event, as recognised by coal petrology and
      mesofossil content: Singhisporites surangei is dominant before the event, but
      following it, it is subordinate to the new species.The abundance of megaspores
      recovered has allowed recognition of the full range of morphologic variation of
      Singhisporites surangei, which encompasses specimens assigned previously to
      Singraulispora Pant & Mishra, 1986 and Mammilaespora Pant & Srivastava, 1961;
      both are regarded as junior synonyms of Singhisporites Potonie, emend.
      Ultrastructurally, the new species shows affinities with Mesozoic isoetalean
      megaspores.

PMID- 10930607
TI  - Pollen fall-out from a tropical vegetation mosaic.
AB  - Pollen fall-out into 60 Oldfield traps set in 11 localities and a variety of
      vegetational contexts on an upland in tropical northeast Australia, range from
      0.5k to 20k (mean 3.5k)grcm(-2)a(-1). The ranges attributable to the four major
      vegetation types in which the traps were situated overlap to such an extent as
      would make it virtually impossible to allocate an 'unknown' pollen count to a
      vegetation type on the basis of total pollen influx alone. Nevertheless, the
      composition of the pollen clearly differs according to the vegetation in which it
      is trapped and the amounts of other vegetation types within at least 100m.
      Substantial variations in catches from closely placed traps suggest the influence
      of very local site, including meteorological, conditions on the results. Pollen
      is carried between vegetation types, much less far from rainforest than from
      sclerophyll forest and woodland, regrowth scrub or herbaceous vegetation, but
      there is no numerically significant ubiquitous 'background' fall-out in the
      region. The data impose some constraints on the interpretation of fossil pollen
      spectra but also potentially permit a greater precision in some aspects of such
      applications.

PMID- 10930609
TI  - Living will.

PMID- 10930608
TI  - Leaves of Berberidaceae (Berberis and Mahonia) from Oligocene sediments, near
      Tepexi de Rodriguez, Puebla.
AB  - From the Oligocene Los Ahuehuetes locality, near Tepexi de Rodriguez, Puebla,
      Mexico, five new plant species are described based on their leaf architecture.
      The presence of brochidodromous or acrodromous venation, and secondary veins
      forming angular (versus rounded) arcs, are well defined characters in the fossil
      material that relate it to Berberidaceae. Comparison with the leaves and leaflets
      of extant and fossil plants allow the recognition of one Mahonia and four
      Berberis new species. The lack of detailed information on leaf architecture in
      Berberidaceae limits the evaluation of the taxonomic relationships that can be
      suggested between fossil and extant plants. However, from a biogeographic point
      of view the presence of these new fossil plants supports the hypothesis of a
      North American origin of the Orientalis Groups of Mahonia, to which a lineage of
      Berberis may be added. Furthermore, two of the new species suggest the dispersal,
      some time during the Tertiary, of a lineage that today forms the Australis Group
      of Berberis from low latitude North America to South America. The movement of the
      Chortis Block is proposed as an alternative to explain the dispersal of a growing
      list of plants from north to south in the Americas. Only through future
      geological and palaeobotanical work can this hypothesis be corroborated.

PMID- 10930610
TI  - We should be careful.

PMID- 10930611
TI  - Rectal prolapse: an update.

PMID- 10930612
TI  - Hospitalists: will hospitalists care for our surgical patients?

PMID- 10930613
TI  - Laparoscopic hernia repair: how would you have your hernia fixed?

PMID- 10930614
TI  - Intracranial aneurysms.

PMID- 10930615
TI  - Sound mind in a sound body.

PMID- 10930616
TI  - Barrett's esophagus and prophylaxis for adenocarcinoma.

PMID- 10930617
TI  - Isolated limb perfusion: is it a useful technique or a futile last gasp?

PMID- 10930618
TI  - Pancreatic cancer: a current overview.

PMID- 10930619
TI  - Evaluating the neck for injury.

PMID- 10930620
TI  - E-mail tips, tricks, and trouble spots: part 1.

PMID- 10930622
TI  - Affirmative action in medicine*

PMID- 10930621
TI  - Grand rounds in general surgery.

PMID- 10930623
TI  - What American surgeons read: a survey of a thousand Fellows of the American
      College of Surgeons.
AB  - PURPOSE: The modern American surgeon is immersed in an ever-deepening sea of
      printed and electronic information. Although publishers know how many books and
      journals they sell, and journals can quote their calculated impact factor, no
      information exists whatsoever about what surgeons read. Which surgical journals
      are "popular," and how does it compare with their impact factor (IF)? Our
      objective was to assess the sources of information and reading habits of American
      surgeons and to compare the "popularity" of journals with their IFs.A
      questionnaire was mailed to 1000 American surgeons, randomly selected from a list
      provided by the American College of Surgeons.A total of 418 surgeons responded,
      and 371 responses could be analyzed (37%). The leading sources of medical
      information were medical literature (93%), professional meetings (88%), and CME
      courses (69%). The average time per surgeon/month dedicated to medical literature
      was 14 hours (range, 1 to 120). Peer-reviewed journals were read by 95%,
      textbooks by 68%, and update series by 60% of the respondents. The three most
      popular surgical journals were Annals of Surgery (IF, 5.40), selected by 60%;
      Journal of the American College of Surgery (IF, 1.87), selected by 48%; and
      Archives of Surgery (IF, 2.53), selected by 36%. The most popular subspecialty
      journals were Cancer (IF, 3.66), selected by 31%; Critical Care Medicine (IF,
      3.74), selected by 17%; and Gastroenterology (IF, 10.33), selected by 12%. The
      New England Journal of Medicine (IF, 28.66), selected by 67%, and the Journal of
      the American Medical Association (IF, 9.55), selected by 66%, were the most
      popular general medical journals, followed by Mayo Clinic Proceedings (IF, 1.98),
      selected by 16%. Among the "leaders" on the IF list for international, British
      medical and surgical journals were Lancet (IF, 11.79), selected by 5%, and
      British Journal of Surgery (IF, 2.38), selected by 0.5% of the respondents.Those
      American surgeons responding consider published literature as their chief source
      of information, especially peer-reviewed journals. Overall, they ignore non
      United States publications and select the journals they read without considering
      its IF.

PMID- 10930624
TI  - Electrosurgery 201: basic electrical principles.

PMID- 10930625
TI  - APACHE.

PMID- 10930626
TI  - Inhibition of complement alternative pathway function with anti-properdin
      monoclonal antibodies.
AB  - Complement activation products appear to contribute to the pathology of several
      acute and chronic inflammatory conditions. The relative contributions of the
      classical and alternative complement pathways to these pathologies have, in large
      part, been undefined. Considerable progress has been made recently in identifying
      inhibitors of complement activation and demonstrating that such molecules can
      attenuate inflammation in various models of disease. However, most of these
      complement inhibitors affect aspects of both the classical and alternative
      pathways. In an effort to better define the role of the alternative complement
      pathway in complement-mediated inflammatory conditions, we have developed
      monoclonal antibodies that specifically inhibit alternative pathway function.
      These blocking antibodies bind human properdin with high avidity and prevent its
      interaction with the alternative pathway C3 convertase. This results in a
      cessation of alternative pathway function in several in vitro assay systems. When
      tested in a model of cardiopulmonary bypass, in which human blood passes through
      tubing, a selected antiproperdin antibody caused nearly complete inhibition of
      the C3a and C5b-9 formation that was seen in untreated blood. Moreover, the anti
      properdin agent resulted in a dramatic reduction of neutrophil and platelet
      activation in the bypass model. Surprisingly, the monoclonal antibody also caused
      a significant inhibition of C5b-9 generation when classical pathway activators,
      such as heparin-protamine or immune complexes, were added to human blood. These
      latter data suggest that the alternative pathway contributes significantly to the
      formation of complement activation products in blood when the classical pathway
      is initially triggered.

PMID- 10930627
TI  - Hb(64-76) epitope binds in different registers and lengths to I-Ek and I-Ak.
AB  - The nature of peptide binding to MHC molecules is intrinsically degenerate, in
      what, one given MHC molecule can accommodate numerous peptides which are
      structurally diverse, and one given peptide can bind to different alleles. The
      structure of the MHC class II molecules allows peptides to extend out of the
      binding groove at both ends and these residues can potentially influence the
      stability and persistence of peptide/class II complexes. We have previously shown
      that both I-E(k) and I-A(k)-restricted T cell hybridomas could be generated
      against the Hb(64-76) epitope. In this study, we characterized the binding
      register of the Hb(64-76) epitope to I-A(k), and showed that it was shifted by
      one residue in comparison to its binding to I-E(k), and did not use a dominant
      anchor residue at P1. This conclusion was further supported by the modeling of
      the Hb(64-76) epitope bound to I-A(k), which revealed that all of its putative
      anchor residues fit into their corresponding pockets. We identified the naturally
      processed Hb epitopes presented by both I-E(k) and I-A(k), and found that they
      consisted of different species. Those associated with I-A(k) being 20-22 residues
      long, whereas, those found to I-E(k) contained 14-16 residues. These findings
      suggested that the lack of a dominant P1 anchor could be compensated by the
      selection of longer peptides. Overall, these studies revealed the Hb(64-76)
      epitope bound to I-E(k) and I-A(k) in distinct registers and lengths,
      demonstrating the plasticity MHC molecules have in generating distinct TCR
      ligands from the same amino acid sequence.

PMID- 10930628
TI  - The extracellular domain of CD4 regulates the initiation of T cell activation.
AB  - To assess the respective contribution of the extracellular and intracellular
      domains of CD4 in regulating early T cell activation events, we have used a CD4
      independent murine T cell clone transfected with human CD4. Stimulation of CD4
      positive clones could only be observed if CD4 molecules associated to lck were co
      aggregated with the TCR complex, confirming that the simultaneous interaction of
      MHC class II molecules with the CD4/lck complex and the TCR is required to
      initiate T cell activation. To assess the involvement of the extracellular
      portion of CD4 in this process, we transfected a chimeric molecule (EGFRCD4)
      consisting of the extracellular portion of the epidermal growth factor receptor
      (EGFR), and of the transmembrane and cytoplasmic domains of human CD4. Although
      this chimeric molecule associates with lck, transfected clones were induced to
      proliferate by mAb specific for TCR in the absence of co-aggregation. A new
      regulatory role for the extracellular domain of CD4 which is independent of its
      interaction with MHC class II molecules is thus revealed in these experiments.
      Taken together, our results demonstrate that, in a CD4-independent cell line, two
      domains of CD4 regulate early T cell activation events: (1) its association with
      lck and (2) its extracellular domain, independently of its interaction with MHC
      class II molecules.

PMID- 10930629
TI  - Repertoire analysis in human immunoglobulin heavy chain minilocus transgenic,
      muMT/muMT mice.
AB  - Mice transgenic for the human immunoglobulin heavy chain minilocus pHCl were
      developed several years ago to help better understand the mechanisms of VDJ
      recombination and antibody response. Interestingly, these minilocus transgenic
      mice develop a polyclonal, extremely diverse mu human immunoglobulin heavy chain
      repertoire, but when immunized, they exclusively use murine immunoglobulin heavy
      chains. Here, the data shows that when the minilocus is transferred by cross
      breeding onto the muMT background, the resulting mice (HCl-muMT/muMT mice)
      develop polyclonal, extremely diverse mu and gamma1 human immunoglobulin heavy
      chain repertoires. Our data indicates that if no antigen specific antibodies are
      detected in pHCl transgenic mice, it is essentially due to competition with
      endogenous immunoglobulin heavy chain gene segments. Moreover, the data shows
      that despite the presence of only one functional V(H) gene segment and despite mu
      and gamma1 repertoires similar to the early pre-immune human repertoire, HCl
      muMT/muMT mice, can develop immune responses against proteins and haptens.
      Finally, the data shows that in aged HC1-muMT/muMT mice, the generation of new B
      cells may be impaired and old mice may mainly rely on B-cell generated earlier in
      life to mount immune responses.

PMID- 10930630
TI  - Reaction with, and fine structural recognition of polyamines by human IgE
      antibodies.
AB  - Human IgE antibodies from nine allergic subjects were found to react with poly-L
      lysine (PLL) and other polyamines. Radioimmunoassay inhibition studies indicated
      that the two amino groups, but not the carboxyl, in lysine contributed to the
      antibody binding and 4-aminomethyl-1,8-octanediamine, a compound containing three
      primary amino groups, was a better inhibitor than compounds containing only two
      primary amino groups. Ethylamine showed weak but clear inhibition indicating that
      even a single amino group could bind to the antibody combining site. Substituted
      ethanolamine and quaternary ammonium compounds were well recognized by some sera
      but with others, substitution hampered recognition. Inhibition studies with
      compounds containing an amino and a carboxyl group at different distances
      revealed that an adjacent carboxyl group interfered with recognition of the amino
      group by some IgE antibodies. IgE binding to PLL was examined at different pHs
      and ionic strengths. Binding was greatest at pH 5-6 to 8 and decreased markedly
      outside this range. Ionic strengths higher than 0.3 M significantly diminished
      the binding. These results indicated that binding of specific antibody to
      polyamine was due to electrostatic interactions of positively charged amino
      groups in the polyamine with the antibody combining site. These results may be
      relevant to mechanisms underlying recognition of some allergens in some atopic
      conditions.

PMID- 10930631
TI  - The novel human IgE epsilon heavy chain, epsilon tailpiece, is present in plasma
      as part of a covalent complex.
AB  - Several splice variants of the secreted human epsilon heavy chain have previously
      been identified by reverse transcription-PCR. The heavy chain of one isoform, IgE
      tailpiece, differs from the originally identified IgE, IgE classic, by the
      replacement of the 2 carboxy-terminal amino acids by 8 novel amino acids
      including a carboxy-terminal cysteine residue. Recombinant human epsilon
      tailpiece and epsilon classic heavy chains were expressed and secreted as H2L2
      monomers in Sp2/0 murine myeloma cells. We have investigated the in vitro
      function and in vivo occurrence of epsilon tailpiece heavy chains using receptor
      binding assays, granule release assays, flow cytometry, half-life studies,
      immunoprecipitation, SDS-PAGE, two-dimensional SDS-PAGE, and Western blotting.
      IgE tailpiece and IgE classic exhibited similar in vivo half-lives in BALB/c
      mice, bound the human high- and low-affinity IgE receptors with similar
      affinities and triggered equivalent levels of high affinity IgE receptor induced
      degranulation. In humans, IgE classic is present as a 190 kD circulating protein
      in vivo. In contrast, we found that in plasma epsilon tailpiece was primarily
      present as part of covalent complexes of approximately 300 and 338 kD.
      Dissociation of the complexes revealed that two species of epsilon tailpiece
      heavy chains were present therein and surprisingly, these in vivo derived epsilon
      tailpiece heavy chains were approximately 5 and 10 kD smaller than the
      recombinant expressed epsilon tailpiece or epsilon classic heavy chains. These
      results show that epsilon tailpiece is present in novel covalent complexes in
      humans.

PMID- 10930633
TI  - Proteomic analysis of T cell activation in the presence of cyclosporin A:
      immunosuppressor and activator removal induces de novo protein synthesis.

PMID- 10930632
TI  - Stability of the B cell antigen receptor complex.
AB  - The B cell antigen receptor (BCR) comprises the membrane-bound immunoglobulin
      (mIg) molecule and the Ig-alpha/Ig-beta heterodimer. By comparing the stability
      of the IgD-BCR and IgM-BCR in different detergent lysates, we find that the IgD
      BCR is more stable than the IgM-BCR. Analysis of chimeric mIgD molecules suggests
      that the deltam transmembrane region is responsible for the more stable
      association of mIgD with the Ig-alpha/Ig-beta heterodimer. Further, the
      differential glycosylation of Ig-alpha molecules, in the two different BCR
      complexes, is determined solely by the ectodomains of the mIg molecules. The
      implications of these findings for the intracellular transport and the signalling
      capacity of the BCRs are discussed.

PMID- 10930634
TI  - Cervical lymphadenitis due to non-tuberculous mycobacteria: surgical treatment
      and review.
AB  - A retrospective study was carried out on 57 children, presenting with non
      tuberculous mycobacterial (NTM) lymphadenitis of the head and neck, over a 12
      year period. Cultures recovered 56 Mycobacterium avium-intracellulare (MAI), and
      one Mycobacterium kansasaii. Anti-mycobacterial agents were used in seven
      patients only. On the basis of the initial operation there were two groups. Group
      1 (11 patients) had an excision, and Group 2 (46 patients) had incision and
      drainage (30 patients), incision and curettage (13 patients), or aspiration
      (three patients). There was no significant difference in the makeup of these two
      groups. However, Group 1 had significantly lower number of re-operations than
      Group 2, P<0.01, and achieved a significantly greater healing rate than Group 2,
      P<0.001. In Group 2 those who had an excision following failure of the first
      operation were significantly more likely to heal than those who did not, P<0.
      005. Operative excision gives a lower rate of re-operation, and a higher rate of
      healing than other procedures. The treatment, natural history, clinical
      presentation, pathogenesis, and diagnosis of NTM cervical lymphadenitis are
      discussed.

PMID- 10930635
TI  - Associations between the eustachian tube and craniofacial skeleton.
AB  - OBJECTIVE: Growth and development of the anatomic region where the Eustachian
      tube (ET) is located are associated with the parameters related to other parts of
      the craniofacial skeleton (CFS). It has been suggested that ET dysfunction is as
      an important factor in pathogenesis of otitis media in childhood which is
      associated with its postnatal growth and development process. The purpose of this
      study was to evaluate associations of length of the ET with various craniofacial
      parameters. METHODS: On lateral cephalometric radiographs of 50 Japanese adult
      (25 male and 25 female), the dimension of the region where the ET is located
      ('length of the ET') and 22 (15 linear and seven angular) craniofacial parameters
      were measured by using a digitiser and computer. Correlation and regression
      analyses were performed between this dimension and other craniofacial parameters.
      RESULTS: It was found that the dimension of the region in which the ET is located
      ('length of the ET') was associated with many craniofacial parameters belonging
      to different subunits of the CFS. However, the stepwise regression analysis
      showed that total cranial base length, posterior upper face height and maxillary
      depth had determinative effects on this dimension. CONCLUSION: Development of the
      ET was associated with development of the cranial base and nasomaxillary complex.
      Therefore, it could be hypothesised that any cessation or aberration in these
      parts of the CFS cause corresponding imbalances in the ET, which may predispose
      to otitis media.

PMID- 10930636
TI  - Relief of posttonsillectomy pain with low-dose tramadol given at induction of
      anesthesia in children.
AB  - OBJECTIVE: Pain is major problem regarding quality of life in children undergoing
      tonsillectomy. Preemptive analgesia by medicine given before commencement of
      surgery is a new way recommended for relief of pain during and after operation.
      The purpose in this study to evaluate preemptive efficacy and safety of lower
      dose of tramadol, which was recently introduced in children undergoing
      tonsillectomy. METHODS: This study was performed on 45 children undergoing
      tonsillectomy with or without adenoidectomy as a double-blinded trial, by using
      tramadol in two dosages (1 and 0.5 mg kg(-1)) and placebo. Pain assessment was
      done by facial pain score (FPS), visual analog scale (VAS) and postoperative
      analgesic requirement; further, duration of anesthesia and duration of awakening
      time, heart rate (HR) and mean arterial pressure (MAP) during and after
      anesthesia, postoperative nausea and vomiting (PONV) and recall of intraoperative
      events were recorded. RESULTS: It was found that 73% children in placebo group
      needed analgesic medicine at the end of the first hour after operation, although
      no analgesic medicine was needed in tramadol groups (chi(2) test, P<0.001).
      However, statistically significant decrease in FPS and VAS in tramadol groups
      were only found up to 15th and 30th min after operation, respectively (Kruskall
      Wallis test, P<0.05). On the other hand, intraoperative HR (10th, 20th and 30th
      min) and MAP (10th and 20th min) were found to be higher in placebo groups (ANOVA
      variance analysis, Tukey-Kramer test adjusted paired t-test, P<0.001 and <0. 01,
      respectively). No significant difference was found in the other parameters, and
      no surgical complication and adverse side effect were occurred in this number of
      study sample. CONCLUSION: Tramadol in lower doses (0.5-1 mg kg(-1)) was an
      efficient preemptive analgesic that could be used at induction of anesthesia in
      adenotonsillectomies of children for providing both good analgesia during
      operation as supplementation to propofol anesthesia and postoperative analgesia
      in only early period.

PMID- 10930637
TI  - Bronchial granuloma - where's the foreign body?
AB  - Airway masses are uncommon in children. The majority of bronchial tumors are
      granulomata secondary to an inhaled foreign body. However, other rare diseases
      like primary bronchopulmonary tumors should always be considered in the
      evaluation of a bronchial granuloma in children. The differential diagnosis of
      bronchial granuloma is presented. We report a 7-year-old girl with a 3-year
      history of recurrent cough and fevers who was found to have a bronchial granuloma
      in the left upper lobe bronchus. The diagnosis of foreign body-related granuloma
      was eventually made after combined and repeated rigid and flexible bronchoscopy.
      This case highlights the need to search aggressively for a foreign body in the
      presence of an airway granuloma in children, even in the absence of a history of
      aspiration.

PMID- 10930638
TI  - Congenital midline submandibular sinus tract.

PMID- 10930639
TI  - Rhinolith of the nasal septum.
AB  - We report an unusual case of rhinolith in the nasal septum in an 11-year-old
      girl. The rhinolith was detected on X-radiographs made for the planning of an
      orthodontic treatment. There were no symptoms like nasal obstruction, chronic
      infection or epistaxis in the young patient. The histopathologic examination
      after surgical removal showed hyaline cartilage, local fibrosis and pronounced
      hemosiderosis, indicating possible prior bleeding. Therefore, an endogenic
      etiology of the intraseptal rhinolith, e.g. a prior trauma of the nasal septum,
      is assumed. A review of the literature is included.

PMID- 10930640
TI  - Airway obstruction caused by a congenital epiglottic cyst.
AB  - Congenital epiglottic cyst is a rare affliction with potential for airway
      obstruction. A newborn boy was referred to our department for evaluation of
      respiratory distress and inspiratory stridor 7 h after birth. Through a
      transnasal fiberoptic laryngoscopy examination, a diagnosis of an obstructive
      upper laryngeal cyst was made. Immediate endoscopic surgery was performed 20 h
      after birth to completely remove the lesion. Two days after surgery, the patient
      resumed normal breathing pattern and showed no further episodes of stridor or
      airway obstruction.

PMID- 10930641
TI  - Six cases of fibromatosis of the head and neck in children.
AB  - Six cases of aggressive fibromatosis occurring in the head and neck in children
      are described. Fibromatosis is a rare, benign but locally infiltrative condition.
      Primary excision is not always possible in the head and neck areas. It is not
      always appropriate to treat children using the same modalities as adults due to
      associated growth problems. The case histories illustrate the management
      difficulties that can be encountered when treating the paediatric population.

PMID- 10930642
TI  - Resistance of influenza viruses to neuraminidase inhibitors--a review.

PMID- 10930643
TI  - Inhibition of human papillomavirus type 16 gene expression by
      nordihydroguaiaretic acid plant lignan derivatives.
AB  - Several methylated derivatives of a plant lignan, nordihydroguaiaretic acid
      (NDGA) were found to be potent anti-viral agents by suppressing Sp1 regulated
      transcription within the sexually transmitted viruses human immunodeficiency
      virus (HIV) and herpes simplex virus (HSV). A prominent Sp1 DNA binding site
      within many human papillomavirus (HPV) promoters has been noted to play an active
      role in HPV gene expression. In this report it is shown that the three NDGA
      derivatives, Mal.4, M(4)N, and tetra-acetyl NDGA can also inhibit gene expression
      from the early promoter P(97) of HPV16. The drug activity on gene expression was
      measured after DNA transfection of recombinant vector constructs linking the
      viral promoter and enhancer elements to the luciferase reporter gene. Using the
      specific luciferase activity as the indicator of gene expression, Mal.4 and M(4)N
      were found to be active in a dose dependent manner that is in the same range of
      concentrations reported for the promoters of HIV, HSV, and simian virus 40 (SV40)
      while tetra-acetyl NDGA was much more active in suppression of the HPV P(97)
      promoter activity than Mal.4 and M(4)N. The drugs showed limited to no effect on
      gene expression driven by the adenovirus major late promoter and the
      cytomegalovirus (CMV) promoter. Hence, such drug derivatives may be significant
      in the therapy of papillomavirus infections and their associated induced human
      cancers.

PMID- 10930644
TI  - Retinoic acid reduces the yield of herpes simplex virus in Vero cells and alters
      the N-glycosylation of viral envelope proteins.
AB  - Treatment of Vero cells with all-trans-retinoic acid (RA) decreased the
      production of infectious herpes simplex virus (HSV) by 1000-10000-fold when
      compared with control cultures. Levels of total HSV envelope glycoproteins gB, gC
      and gD produced following RA treatment, were comparable with those found in
      control cultures. Following 24 h of RA treatment, lower molecular weight variants
      of gB, gC and gD were produced in addition to the typical molecular mass of each
      protein found in control samples. Between 24 and 48 h of RA treatment, the
      proportion of the lower molecular mass variants increased. When control and RA
      treated samples were incubated with peptide N-glycosidase F (PNGase F), which
      removes N-glycosylated sugars, the molecular weights of the respective gB, gC and
      gD proteins produced were comparable in both the groups, indicating that RA did
      not alter the primary sequence of viral proteins during protein synthesis or
      increase viral protein proteolysis. RA treatment increased [3H]mannose
      incorporation into glycoproteins in HSV infected cells but did not change
      [3H]glucosamine incorporation. We conclude that RA treatment does not reduce the
      synthesis of three major viral envelope glycoproteins but alters their N
      glycosylation and postulate that the inhibitory effect of RA is related to its
      action on N-glycosylation.

PMID- 10930645
TI  - Antiviral activity of NMSO3 against respiratory syncytial virus infection in
      vitro and in vivo.
AB  - NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory
      syncytial virus (RSV) and other myxovirus infections in cell culture. The median
      effective concentration (50% effective concentration, EC(50)) of NMSO3 against
      replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 microM by
      optical ELISA and the plaque reduction method, respectively. On the other hand,
      the corresponding values for ribavirin were 10.5 and 11.2 microM, respectively.
      NMSO3 showed potent activity against other laboratory strains as well as fresh
      clinical isolates of RSV, and the average EC(50) was similar to that for Long
      strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero
      cells for which the median cytotoxic concentration (CC(50)) was more than 685
      microM. The selectivity index [SI=(CC(50) for HEp-2/EC(50))] of NMSO3 for RSV
      exceeded 2978 and that of ribavirin was 6. The EC(50) of NMSO3 against influenza
      virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8
      microM by the TCID(50) method using MDCK cells. NMSO3 did not inhibit replication
      of influenza B virus, parainfluenza virus type 2 and canine distemper virus at
      103 microM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added
      between 0 and 1.5 h after virus infection. By a temperature shift experiment
      during the period of contact between the virus and cells, NMSO3 inhibited both
      the binding of RSV to the cells and its penetration into the cells. Prophylactic
      and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was
      examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton
      rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day
      every day, decreased the RSV titer in lungs to 10(-1.26) to 10(-1.63) compared to
      the control rats which were infected with RSV and left untreated.

PMID- 10930646
TI  - Comparison of ultraviolet-induced genotoxicity detected by random amplified
      polymorphic DNA with chlorophyll fluorescence and growth in a marine macroalgae,
      Palmaria palmata.
AB  - The random amplified polymorphic DNA (RAPD) technique was used to detect DNA
      damage in the sublittoral macroalgae Palmaria palmata (Rhodophyta) exposed to
      both ambient and elevated irradiances of UV-B (280-315 nm). To investigate the
      potential of this method in ecotoxicological assessments, the qualitative and
      quantitative modifications in RAPD profiles were compared with changes in a
      number of physiological and fitness parameters. RAPD detectable modifications in
      DNA profiles were observed in all UV exposed individuals compared with controls.
      Changes in chlorophyll fluorescence (F(v)/F(m) ratio), in vivo pigment
      absorptance, thallus growth and RAPD profiles, examined simultaneously, provided
      a sensitive measure of UV-induced toxicity. In conclusion, the application of the
      RAPD method in conjunction with other suitable physiological and fitness
      measurements, may prove to be a valuable tool for investigating the specific
      effects of genotoxic agents upon marine algal populations. Ultimately, this
      methodology may allow the ecotoxicological examination of the link between
      molecular alterations and measurable adverse effects at higher levels of
      biological organisation.

PMID- 10930647
TI  - A modified mercury saturation assay for measuring metallothionein.
AB  - A thorough re-evaluation of assay procedures for a mercury displacement
      analytical method for metallothionein (MT) described in 1993, was conducted using
      an analytical standard of rabbit liver MT-II and MT determinations, in liver,
      kidney, gill and intestine from lake trout (Salvelinus namaycush). These studies
      indicated that: (1) loss of MT by adherence to polypropylene material occurs with
      the dilution series; (2) use of a calibration curve using a rabbit liver MT-II
      analytical standard, is superior to the dilution series for determining unknown
      MT concentrations; (3) Hg incubation time requirements are less in 20% TCA than
      in 10% TCA; and (4) employing both 20% TCA and heat at 95 degrees C for 5 min to
      denature non MT proteins results in the most accurate MT spike recoveries, or
      recoveries that did not differ significantly from those closest to 100%, in
      liver, kidney, gill and intestine. Calibration curves with an average r(2) of
      0.9998 for 69 trials over different days, while passing through the origin,
      provided evidence of negligible non-specific binding of mercury. Use of water or
      saline for preparing tissue homogenates, produced slight, but significant,
      differences in MT estimates in the intestine and kidney. Comparisons between the
      original and the modified methods were made on liver, kidney and gill from
      control, sham-injected and Cd-treated lake trout. Differences in MT estimates
      obtained between the two methods depended upon the tissue. MT estimates in liver
      by the modified method were 9, 13, and 10% higher in control, sham-injected and
      Cd-treated groups, respectively, than those resulting from the original assay. MT
      estimates in gill by the modified method, were 3.2-fold, 4.0-fold and 69% higher
      in control, sham-injected, and Cd-treated groups, respectively. Corresponding
      values for kidney were 37, 75, and 57% higher. Because percent recoveries of MT
      II spikes were virtually 100%, in all four tissues, using the modified method, MT
      estimates obtained using these modifications were more accurate than those
      obtained using the procedures of the original assay. Application of the modified
      assay to fish tissues in a Canadian biomonitoring program for metal mining,
      demonstrated that in 1 week an experienced technologist can complete 90 MT
      analyses of liver and kidney and 75 analyses of gill and intestine.

PMID- 10930648
TI  - Study on the free amino acid levels in the hemolymph, gill, hepatopancreas and
      muscle of Penaeus monodon exposed to elevated ambient ammonia.
AB  - Tiger shrimp Penaeus monodon following 24 h exposure to 0.002 (control), 0.072
      and 0.718 mM ammonia were examined for the free amino acid (FAA), ammonia and
      urea levels in the hemolymph, gill, hepatopancreas and muscle. Control shrimps
      contained total FAA in hemolymph (1.19 umol ml(-1)), gill (21.81 umol g(-1)),
      hepatopancreas (100.81 umol g(-1)) and muscle (239.54 umol g(-1)). Glycine and
      arginine were the major contributors to the total FAA pool, and made up of 90% of
      the total FAA in the muscle of P. monodon. The total FAA level in the hemolymph
      increased directly with ambient ammonia, whereas the total FAA level in the
      hepatopancreas was inversely related to ambient ammonia. No significant
      difference of total FAA was observed in the gill and muscle among the shrimps in
      three treatments. Ammonia level increased by 160% in hemolymph, 105% in gill,
      236% in hepatopancreas and 68% in muscle for the shrimps exposed to 0.718 mM
      ammonia. Urea and ornithine in the hepatopancreas increased by 107 and 1446%,
      whereas arginine level in the hepatopancreas decreased by 50% for the 0.718 mM
      ammonia-exposed shrimps. Decreases of arginine and other FAA with a concomitant
      increase of ornithine and urea level in the hepatopancreas indicated catabolism
      of FAA and ureogenesis. Increases of ammonia, urea, taurine, glutamine, proline,
      alanine, glycine and asparagine in the hemolymph revealed a intracellular
      osmoregulation for P. monodon under the stress of ambient ammonia at 0.718 mM.

PMID- 10930649
TI  - The adaptation of mussels Crenomytilus grayanus to cadmium accumulation result in
      alterations in organization of microsomal enzyme-membrane complex (non-specific
      phosphatase).
AB  - The kinetic parameters (V(m), K(m) and slope) of membrane-bound microsomal non
      specific phosphatase (NPase, with G6P as the substrate) from the digestive gland
      of unexposed and cadmium adapted (45 days for 100 ug Cd(2+)/l) mussels were
      investigated. In vivo and in vitro approaches were used. Adaptation of mussels
      (Crenomytilus grayanus) to cadmium resulted in a 1.6-fold increase in NPase
      activity. V(m) was increased by 1.6-fold, but K(m) was the same in terms of
      enzyme kinetics. This indicates that the total concentration of the enzymes in
      the digestive gland increased. Cd(2+) (1 mM) did not significantly alter the
      activity of the membrane-bound enzyme in vitro both for unexposed and for cadmium
      adapted mussels, meaning that cadmium ions are not a direct inhibitor of the
      membrane-bound enzyme in this concentration. The microsomal NPase activity in
      both unexposed and cadmium adapted mussels was inhibited by in vitro
      solubilization of microsomes with non-ionic detergent (Triton X100, 0.01%). This
      inhibition was uncompetitive for microsomes of unexposed mussels (K(m) decreased
      3.1-fold). The most drastic events were observed in cadmium adapted mussels,
      where inhibition was mixed (K(m) decreased 7.2-fold). The simultaneous actions of
      detergent and cadmium ions did not alter NPase activity significantly in
      comparison with action of the detergent alone. The differences in the types and
      the extents of inhibition of the enzymes activity by membrane disordering agent
      (Triton X100) indicated that the enzyme-membrane complex (NPase) has been altered
      as a result of adaptation of mussels to cadmium accumulation. We conclude that
      the mussels produced a new enzyme-membrane complex, with the same K(m) as the
      previous complex, but with other detergent sensitivity and greater amounts. Thus,
      the adaptation capacity of this enzyme is reduced as result of adaptation of
      mussels to cadmium accumulation.

PMID- 10930650
TI  - Biomarkers in zebra mussels (Dreissena polymorpha) for the assessment and
      monitoring of water quality of the St Lawrence River (Canada).
AB  - Five biomarkers (MT: metallothionein-like proteins, EROD: ethoxyresorufin ortho
      deethylase, DNA strand breaks, LPO: peroxidation of lipids, VG: vitellogenin-like
      protiens) were measured in the soft tissues of zebra mussels (Dreissena
      polymorpha) in order to assess the spatial variation of exposure to contaminants
      along the St Lawrence River (Canada). Fifteen mussels >25 mm shell length were
      analyzed from each of the 13 sampling sites. Significant differences between
      sites were noted for all biomarkers, but the general level of variability was
      low. Three biomarkers (DNA, LPO and VG) exhibited a similar pattern of spatial
      variation while MT and EROD had distinct and specific patterns. MT had the
      strongest discriminating power and EROD showed the largest range of variation
      among sites. Highest biomarker responses were measured in specimens from local
      contaminated sites such as harbors and industrial sectors. A positive
      relationship was found between MT and copper (Cu), but no significant correlation
      was observed between other biomarker responses and the levels of ten trace metals
      bioaccumulating in the zebra mussels tissues. Results indicate that the
      measurement of biomarker responses is technically feasible. The performance of
      each biomarker is assessed in the context of the role and advantages of selecting
      a battery of biomarkers for detecting contamination problems. The use of zebra
      mussels as a sentinel species for biomonitoring potential toxic effects in situ
      is discussed.

PMID- 10930651
TI  - Recovery of Penaeus monodon from functional anaemia after exposure to sublethal
      concentration of nitrite at different pH levels.
AB  - Tiger shrimp Penaeus monodon (14.79+/-0.19 g) which had been exposed individually
      to 0.72 mM nitrite at pH 6.8, 8.2 and 9.8 after 3, 6, 12, 24 and 48 h were
      examined for the water nitrite concentration, hemolymph nitrite, oxyhemocyanin,
      protein and osmolality levels. Same parameters were examined for shrimp depurated
      in nitrite-free water after 3, 6, 12 and 24 h following 48 h exposure to nitrite.
      In the nitrite-exposed test, nitrite influx, hemolymph nitrite and osmotic
      differential (medium osmolality - hemolymph osmolality) increased with exposure
      time, and were higher at pH 6.8, whereas water nitrite concentration,
      oxyhemocyanin, protein, ratio of oxyhemocyanin to protein and hemolymph
      osmolality decreased with exposure time and were lower at pH 6.8. In the
      depuration test, water nitrite concentration increased with depuration time, and
      was higher at pH 6.8, whereas, hemolymph oxyhemocyanin, ratio of oxyhemocyanin to
      protein and hemolymph osmolality increased with depuration time and were higher
      at pH 9.8. Hemolymph nitrite decreased with depuration time, and was 2.52, 2.19
      and 0.24 umol ml(-1) after 6 h at pH 6.8, 8.2 and 9.8, respectively. Nitrite
      entry is considered to occur mainly via the form of nitrous acid (HNO(2)) in
      water uptake. The fact that the hemolymph nitrite decreased to non-detectable
      level with 72-88% recovery of oxyhemocyanin after 24 h depuration suggests an
      occurrence of reductase for nitrite-exposed shrimps.

PMID- 10930652
TI  - Suppression of superoxide production by chlorothalonil in striped bass (Morone
      saxatilus) macrophages: the role of cellular sulfhydryls and oxidative stress.
AB  - Chlorothalonil (TCIN) is the most commonly applied fungicide in the USA, with
      substantial use in the Chesapeake Bay area. Little is known about the sublethal
      toxicity of TCIN to fish, but since it is structurally similar to the
      immunotoxicant pentachlorophenol, the potential for immunomodulation exists.
      Previous studies have indicated that in vitro exposure of macrophages to TCIN
      modulates immunostimulated reactive oxygen species (H(2)O(2)/hypochlorous acid)
      and NADPH production in striped bass (Morone saxatilus). The goals of this study
      were to determine if TCIN inhibits superoxide (O(2)(-)) production by macrophage
      NADPH oxidase, to examine the role of cellular sulfhydryl groups in TCIN-induced
      macrophage dysfunction, and to identify the extent to which lipid peroxidation
      contributes to the observed toxic effects. The results of lucigenin-augmented
      chemiluminescence assays indicated that TCIN suppressed both baseline and
      stimulated O(2)(-) production in a dose-dependent manner. Similar results were
      obtained using both the particulate stimulant zymosan and the lipid-soluble
      stimulant phorbol 12-myristate-13-acetate. Inhibition of glutathione synthesis by
      pre-treatment with buthionine sulfoximine (BSO) enhanced the suppression of O(2)(
      ) production. The protection of sulfhydryl groups by culturing macrophages with
      dithiothreitol (DTT) reduced TCIN-induced macrophage dysfunction. TCIN did not
      initiate lipid peroxidation in macrophages, as measured by the thiobarbituric
      acid reactive substances (TBARS) assay, nor did pre-treatment with BSO potentiate
      lipid peroxidation. Because the observed TCIN-induced suppression of O(2)(-) was
      modulated by altering cellular sulfhydryl status with BSO and DTT, it is possible
      that toxicity results from the inhibition of NADPH oxidase activity by TCIN
      binding to its functional sulfhydryl groups.

PMID- 10930653
TI  - Uptake and effects of nitrite in the marine teleost fish Platichthys flesus.
AB  - The route of NO(2)(-) uptake and subsequent physiological effects were examined
      in the marine teleost, European flounder (Platichthys flesus), during exposure to
      1 mM ambient NO(2)(-) for up to 11 days. Drinking of seawater resulted in a
      similar nitrite concentration in the anterior part of the intestine as in the
      ambient water. The NO(2)(-) concentration decreased along the gastro-intestinal
      tract, suggesting NO(2)(-) uptake across the intestinal epithelium. Comparison of
      NO(2)(-) uptake in fish that drank NO(2)(-)-contaminated seawater with fish that
      did not (i.e. had the intestine perfused with a NO(2)(-)-free saline during
      NO(2)(-) exposure) revealed that the intestinal route contributed some 66% of
      whole-body NO(2)(-) uptake. Plasma [NO(2)(-)] stayed below the ambient level. It
      reached a maximum of 0.35-0.4 mM on days 3-6 and then declined to 0.2 mM on day
      11. The physiological effects of NO(2)(-) exposure were relatively minor compared
      with those reported in freshwater fish. Blood methemoglobin levels increased from
      approximately 4% in non-exposed fish to a maximum of 18% of total hemoglobin in
      exposed fish. An extracellular hyperkalemia was observed from day 3 of NO(2)(-)
      exposure, with a maximal increase in plasma K(+) concentrations of 38%. No
      mortality occurred during the 11 days of NO(2)(-) exposure. The lack of mortality
      can be related to the relatively low NO(2)(-) accumulation in the plasma and the
      relatively minor physiological disturbances.

PMID- 10930654
TI  - Biochemical and (ultra)structural hepatic perturbations of Brachydanio rerio
      (Teleostei, Cyprinidae) exposed to two sublethal concentrations of copper
      sulfate.
AB  - The aim of this study was to compare biochemical and (ultra)structural
      perturbations induced by Cu in the liver of Brachydanio rerio exposed for 14 days
      to sublethal concentrations of copper and then replaced for 14 days to clean
      water. Toxicity of Cu was clearly demonstrated: simultaneously to Cu
      accumulation, the liver developed large lysed areas and hepatocytic alterations.
      However, the majority of the parenchyma was composed of functional dark
      hepatocytes displaying typical feature of increased metabolism: development of
      rough reticulum, increase in size of nucleus and nucleolus, glycogenic depletion.
      Increase in hepatic protein content and of anti-oxidative defences (glutathione
      content, catalase and glutathione-S-transferase (GST) activities) indicated that
      the overall response of the liver was adaptative. In all hepatocytes a cord-like
      structure of the nucleoli was suspected to be associated to metal deposition.
      After 14 days depuration, the liver still contained high Cu concentrations and
      the hepatic alterations were not reversed. Such complementary studies are
      necessary for a better understanding of the deleterious effects of pollutants and
      for the development of biomarkers for metal toxicity.

PMID- 10930655
TI  - Anomalies on capture nets of Hydropsyche slossonae larvae (Trichoptera;
      Hydropsychidae), a potential indicator of chronic toxicity of malathion
      (organophosphate insecticide).
AB  - A laboratory study on the sublethal effects of malathion on the net-spinning
      behavior of the caddisfly larvae Hydropsyche slossonae was conducted in order to
      assess the potential of net anomalies as an indicator of chronic exposure to
      organophosphorus insecticides. Two anomalies were identified after chronic
      exposure to 0.01, 0.05, 0.1, 0.5 and 1.0 ug l(-1) malathion. The first was a
      distortion of the midline meshes where the normal diamond shape structure was
      disrupted and the meshes were separated by extra strands (called 'midline'
      anomaly). The second aberration observed was a significant decrease in net
      symmetry. Both anomalies were highly correlated to the toxic action of malathion,
      i.e. inhibition of the acetylcholinesterase enzyme (AChE). Sodium dodecyl sulfate
      polyacrylamide gel electrophoresis analyses of capture nets did not show any
      modification of silk polypeptides after exposure to malathion, indicating that
      net distortions were not related to silk composition. Both anomalies seem to
      represent the symptoms of the specific toxic action of malathion; nevertheless,
      they can serve as an index of the physiological condition of the larvae,
      especially the midline anomaly. The symmetry of the nets decreased significantly
      after exposure to 0.5 and 1.0 ug l(-1). However, the toxicity curves (EC(50))
      showed that the sensitivity threshold for the midline anomaly ranged from 0.11 to
      0.28 ug l(-1), which reflect more realistic exposure to concentrations expected
      to occur in the field. Hence, the use of capture net anomalies of hydropsychid
      larvae could represent a valuable indicator of sublethal toxicity induced by
      malathion and other organophosphorus insecticides in running waters.

PMID- 10930656
TI  - Hepatic microsomal desulfuration and dearylation of chlorpyrifos and parathion in
      fingerling channel catfish: lack of effect from Aroclor 1254.
AB  - Channel catfish were treated intraperitoneally with 100 mg Aroclor 1254/kg body
      weight and sacrificed at 96 h to observe the effects of this cytochrome P450 1A
      (CYP1A) inducer on chlorpyrifos and parathion metabolism. In the initial
      experiment, hepatic microsomal ethoxyresorufin-O-deethylase (EROD) activity of
      the Aroclor-treated fish was significantly induced but no effects on
      desulfuration or dearylation of chlorpyrifos or parathion were evident. In the
      second experiment, Aroclor 1254 did not alter total hepatic microsomal P450s
      content, but significantly induced hepatic EROD and CYP1A. There were no evident
      effects to other hepatic CYP isoforms recognized by anti-trout CYP2K1, CYP2M1 and
      CYP3A27. These experiments indicate that Aroclor 1254 did not induce the P450s
      responsible for metabolism of the phosphorothionate insecticides.

PMID- 10930657
TI  - An actin-binding protein is involved in pestivirus entry into bovine cells.
AB  - Infection of bovine cells with bovine viral diarrhoea virus (BVDV) can be blocked
      by the monoclonal antibody (mab) BVD/CA 26, which is directed against a cellular
      membrane protein. To characterize this molecule, it was isolated and purified by
      column chromatography. It was found to be an acidic, glycosylated membrane
      protein consisting of two polypeptide chains of about 28 and 56 kDa. Under non
      reducing conditions the chains formed multimers of about 200 kDa. In an actin
      binding assay the 56 kDa polypeptide chain bound to F-actin as judged by co
      sedimentation with actin filaments. Since the target molecule of BVD/CA 26 is
      localized on the surface of living cells and additionally binds to F-actin, a
      possible biological function may be to connect the cortical actin filaments with
      the cellular plasma membrane. The blocking effect of BVD/CA 26 indicates that
      this cellular plasma membrane protein is involved in the endocytic pathway of
      BVDV particles.

PMID- 10930658
TI  - The molecular epidemiology of Kokobera virus.
AB  - We describe herein the molecular epidemiology and phylogeny of Kokobera (KOK)
      virus, a flavivirus found in Australia and Papua New Guinea. We sequenced a
      region encompassing the 200 nucleotides of the 3' terminus of the NS5 gene, and
      the first 300 nucleotides of the 3' untranslated region (UTR). The study included
      25 isolates of the virus, including an isolate from PNG, and several recent
      isolates from the south-west of Western Australia (WA), where the virus had not
      previously been detected. We found that the KOK isolates clustered according to
      geographic location and time of isolation into three distinct topotypes: one
      covering Queensland and New South Wales; another represented by the single
      isolate from PNG; and a third covering the Northern Territory and WA. This latter
      group was further subdivided into northern and south-west isolates. This
      molecular epidemiology is significantly different from other Australian
      flaviviruses, such as Murray Valley encephalitis (MVE) and Kunjin (KUN) viruses,
      which exist as single genetic types across the entire Australian continent.
      However, it is similar to the molecular epidemiology of the alphavirus Ross River
      (RR) virus. This may be explained by the fact that MVE and KUN viruses are known
      to have birds as their main vertebrate hosts, whereas RR virus utilises
      macropods, which have also been implicated as the vertebrate host for KOK virus.
      In addition, the south-west isolates exhibited a degree of sequence
      heterogeneity, including one isolate that has a nine nucleotide deletion in the
      3'UTR. This suggests that KOK virus has been in the south-west of WA for some
      time, and was not recently introduced.

PMID- 10930659
TI  - Episomal expression of a hammerhead ribozyme directed against plum pox virus.
AB  - Two related antisense RNAs directed against plum pox virus (PPV) were expressed
      episomally in Nicotiana clevelandii by infection with recombinant potato virus X
      (PVX). One recombinant PVX expressed an ordinary PPV antisense RNA of about 400
      nucleotides, while the other expressed a related antisense RNA that carried the
      catalytic domain of a hammerhead ribozyme. Inoculation with the latter
      recombinant PVX resulted in the accumulation of ribozyme RNA that was
      catalytically active when tested in vitro with a PPV substrate RNA. Plants that
      had been inoculated with recombinant PVX viruses, expressing either PPV-directed
      antisense or ribozyme sequences or GUS RNA as a control, were challenged with PPV
      by a sequential second inoculation. In plants that expressed PPV antisense
      sequences, the appearance of PPV disease symptoms was delayed for 3-5 days.
      Quantification of PPV 1 week after inoculation showed that the protective effect
      by the episomally expressed catalytic antisense RNA was stronger than that of the
      ordinary antisense RNA. However, eventually all plants tested accumulated
      comparable titers of PPV.

PMID- 10930660
TI  - Cleavage of the respiratory syncytial virus fusion protein is required for its
      surface expression: role of furin.
AB  - The fusion (F) glycoprotein of respiratory syncytial virus (RSV) is synthesized
      as a nonfusogenic precursor protein (F(0)), which during its migration to the
      cell surface is activated by cleavage into the disulfide-linked F(1) and F(2)
      subunits. In the present study, soluble secreted human furin produced by a
      recombinant baculovirus cleaved RSV F(0) into proteins the size of F(1) and F(2).
      Furthermore, cleavage of F(0) was partially inhibited in the furin defective LoVo
      cell line, in calcium depleted HEp-2 cells, and in HEp-2 cells treated with the
      furin inhibitor decanoyl-R-V-K-R-chloromethylketon. These findings strongly
      suggest an important role for furin in activation of the RSV F protein. The F(0)
      protein could not be detected on the surface of cells, in which F protein
      activation was inhibited, and RSV particles did not appear to be released from
      these cells. It thus seems that in contrast to the F proteins of most other
      paramyxoviruses, the RSV F(0) protein is very inefficient in reaching the cell
      surface or is unable to reach the cell surface and therefore cannot be
      incorporated into virus particles.

PMID- 10930661
TI  - Hemifusion activity of a chimeric influenza virus hemagglutinin with a putative
      fusion peptide from hepatitis B virus.
AB  - Entry of enveloped viruses is often mediated by an aminoterminal hydrophobic
      fusion peptide of a viral surface protein. The S domain of the hepatitis B virus
      surface protein contains a putative fusion peptide at position 7-18, but no
      systems are available to study its function directly. We tested the functionality
      of this peptide and a related peptide from another hepadnavirus in the context of
      the well-characterized influenza virus hemagglutinin H7 using gene mutation. The
      chimeric hemagglutinins could be expressed stably in CV 1 cells and were
      transported to the cell surface. The chimeras were incompletely cleaved by
      cellular proteases but cleavage could be completed by trypsin treatment of the
      cells. The chimeras did not differ in receptor binding, i.e. erythrocyte binding.
      Hemifusion and fusion pore formation were detected with membrane or cytosolic
      fluorescent dye-labeled erythrocytes as target structures of the hemagglutinin.
      Five of six different chimeras mediated hemifusion in 20-54% of the hemagglutinin
      expressing cells, complete fusion and syncytium formation was not observed. The
      data suggest that the sequence 7-18 of the hepatitis B S domain may indeed
      initiate the first step of viral entry, i.e. hemifusion.

PMID- 10930662
TI  - Genetic characterization of HIV type 1 and type 2 from Bissau, Guinea-Bissau
      (West Africa).
AB  - Previous studies from Guinea-Bissau (West Africa) have demonstrated a unique
      epidemiology with respect to both HIV-1 and HIV-2 infection. In order to evaluate
      the prevalence and dynamics of HIV-1 and HIV-2 subtypes in Bissau, the capital
      city of Guinea-Bissau, a cross-sectional study was set up using serological and
      molecular techniques. Plasma samples from 103 individuals were screened for HIV-1
      and HIV-2 antibodies by ELISA and Western-blot. Seropositive results were
      confirmed by PCR amplification of proviral sequences in primary peripheral blood
      mononuclear cells (PBMC) with env and LTR primer sets for HIV-2 and env, LTR and
      pol primers for HIV-1. A total of 38/103 individuals were HIV-seroreactive (four
      HIV-1, 15 HIV-2, 19 HIV-1/HIV-2). A total of eight out of 19 dually seropositive
      specimens showed double PCR amplification of HIV-1 and HIV-2 proviral sequences,
      accounting for 21% of the infected individuals. In the remaining 11 individuals
      either HIV-2 or HIV-1 sequences were detected, the majority (n=9) amplifying only
      HIV-2. These screening data demonstrate a high discrepancy between serology and
      PCR results for dually seroreactive samples, Western-blot giving an
      overestimation of double infection. Additionally, HIV-1 strains were subtyped by
      heteroduplex mobility assay (HMA) on the basis of gp120 sequences. Subtyping of
      HIV-2 was carried out by DNA sequencing and phylogenetic analysis of env V3
      molecular clones. For both HIV-1 and HIV-2 strains circulating in Bissau, our
      results indicate dominance of subtype A.

PMID- 10930663
TI  - Induction of growth rate and transcriptional modulation of growth promoters and
      growth inhibitors in epithelial cells by EBV-LMP1.
AB  - LMP1 is a genuine oncogene encoded by the Epstein-Barr virus (EBV). The cellular
      response to expression of the EBV-encoded gene LMP1 in the epithelial cell line
      Wish was studied. Cells were stably transfected with pCEP-LMP, an expression
      vector for LMP1. On transcript level a transient expression of the LMP1-gene with
      a maximum 2 days post transfection was observed. Six days post transfection the
      rate of DNA synthesis of LMP1-transfected Wish cells was increased by 80%
      compared to control cells, after 2 further days the number of cells was increased
      by 32%. A human cDNA-array was screened with probes from LMP1-transfected and
      control cells showing induction of transcription for proliferation associated
      genes and repression for growth suppressor genes.

PMID- 10930664
TI  - Genetic characterization of H3N2 influenza viruses isolated from pigs in North
      America, 1977-1999: evidence for wholly human and reassortant virus genotypes.
AB  - Since 1998, H3N2 viruses have caused epizootics of respiratory disease in pigs
      throughout the major swine production regions of the U.S. These outbreaks are
      remarkable because swine influenza in North America had previously been caused
      almost exclusively by H1N1 viruses. We sequenced the full-length protein coding
      regions of all eight RNA segments from four H3N2 viruses that we isolated from
      pigs in the Midwestern U.S. between March 1998 and March 1999, as well as from
      H3N2 viruses recovered from a piglet in Canada in January 1997 and from a pig in
      Colorado in 1977. Phylogenetic analyses demonstrated that the 1977 Colorado and
      1997 Ontario isolates are wholly human influenza viruses. However, the viruses
      isolated since 1998 from pigs in the Midwestern U.S. are reassortant viruses
      containing hemagglutinin, neuraminidase and PB1 polymerase genes from human
      influenza viruses, matrix, non-structural and nucleoprotein genes from classical
      swine viruses, and PA and PB2 polymerase genes from avian viruses. The HA
      proteins of the Midwestern reassortant swine viruses can be differentiated from
      those of the 1995 lineage of human H3 viruses by 12 amino acid mutations in HA1.
      In contrast, the Sw/ONT/97 virus, which did not spread from pig-to-pig, lacks 11
      of these changes.

PMID- 10930665
TI  - Dissociation of DDB1-binding and transactivation properties of the hepatitis B
      virus X protein.
AB  - The hepatitis B virus (HBV) X protein (HBx) is a transactivator encoded by
      mammalian hepadnaviruses, and is thought to stimulate transcription by
      interacting with one or more host cell factors. Numerous cellular proteins have
      been reported to interact with HBx including a component of the nucleotide
      excision repair complex called ultraviolet damaged DNA binding (UV-DDB, or DDB1)
      protein. Recent studies have identified a role for DDB1 in transcription, raising
      the possibility that HBx may acquire its broad transcriptional properties by
      interacting with DDB1. A panel of HBx mutant proteins, some of which no longer
      bind to DDB1, was used to test this hypothesis. Plasmid DNAs encoding HBx
      wildtype and mutant derivatives were transfected into HepG2 cells, and their
      ability to transactivate a cotransfected reporter plasmid tested. Results from
      the transactivation assays in HepG2 cells were then compared with data obtained
      from HBx-DDB1 binding studies performed in yeast. Several HBx mutant proteins
      unable to bind DDB1 remained competent for transactivation, indicating that HBx
      binding to DDB1 is not required for HBx transactivation of the ETS1 promoter. It
      remains possible that a subset of HBx transactivation function targets an as yet
      undefined DDB1-specific pathway.

PMID- 10930666
TI  - Mutations occurring during serial passage of Japanese equine infectious anemia
      virus in primary horse macrophages.
AB  - An attenuated equine infectious anemia virus (EIAV), named V26, was previously
      obtained after 50 passages of the Japanese virulent strain V70 in primary
      macrophage culture. To clarify the differences between both viruses, their full
      length sequences were determined. There were higher mutations in S2 (6.15% amino
      acid difference) and LTR (10.7% nucleotide difference). The presumed initiation
      codon of the S2 gene was absent from the sequence of V26. There was a large
      insertion within the long-terminal repeat (LTR) U3 hypervariable region of V26.
      In addition, there were minor mutations in gag (1.22% amino acid difference), pol
      (1.05% amino acid difference) and env (1. 65% amino acid difference) regions, but
      no mutation in tat region. No mutations were observed in the principal
      neutralizing domain in the gp90. Thus, the mutations in the S2 and LTR might be
      the major target sites of mutation in EIAV during serial passages in vitro.

PMID- 10930667
TI  - Immunotherapy with mannan-MUC1 and IL-12 in MUC1 transgenic mice.
AB  - Mice immunised with oxidised mannan-MUC1 fusion protein (M-FP) develop MHC
      restricted CD8(+) cytotoxic T cells. We now demonstrate that in MUC1/HLA-A2
      transgenic mice, IL-12 gives enhanced CTL, CTLp and tumor protection. CTLp in
      MUC1 transgenic mice with M-FP were 1/55,000, and with IL-12, this increased to
      1/19,000, with improved tumor protection. Thus, IL-12 is important for effective
      CTL responses to MUC1 in transgenic mice.

PMID- 10930668
TI  - Development of a transgenic mouse neurovirulence test for oral poliovirus
      vaccine: international collaborative study 1993-1999.
AB  - The neurovirulence safety of oral live poliovirus vaccine (OPV) has been tested
      in monkeys, because only primates are sensitive to all three types of poliovirus.
      The genetic engineering of transgenic mice susceptible to poliovirus led to
      studies on the suitability of these mice for a neurovirulence test of OPV. A WHO
      international collaborative study started with type-3 OPV in 1993 and was
      completed in 1999. The study produced a voluminous set of data proving that the
      TgPVR21 mice, inoculated with OPV samples into the lumbar cord, provided a test
      for neurovirulence of OPV as sensitive and reproducible as the monkey test. A
      statistical decision model for acceptance/rejection of type-3 vaccines using the
      transgenic mouse test has been developed. The mouse neurovirulence test showed a
      number of essential advantages over the monkey test. This is the first example of
      a successful introduction of transgenic animals into control of biologicals. In
      October 1999, the WHO Expert Committee on Biological Standardization approved
      TgPVR21 mice as alternative to the monkey model for neurovirulence testing of OPV
      type 3. A final step of the collaborative study with OPV types 1 and 2 is in
      progress, and data obtained so far are promising. Two breeding stations for
      production of TgPVR21 mice are being established in Asia and Europe.

PMID- 10930669
TI  - Immunity to diphtheria and tetanus in England and Wales.
AB  - The immunity profile of the English and Welsh population to diphtheria and
      tetanus has been determined by measuring diphtheria and tetanus antitoxin levels
      for 3088 and 3142 sera, respectively. Time-resolved fluorimetric immunoassay -
      DELFIA was used to measure diphtheria antitoxin levels and an in-house, indirect
      ELISA to measure tetanus antitoxin levels. More than 80% of those aged between 2
      and 20-24 years had protective diphtheria antitoxin levels of 0.01 IU/ml, or
      greater, and more than 80% of those aged between 4 and 35-39 years had protective
      tetanus antitoxin levels of 0.1 IU/ml, or greater. Only 29% and 53% of those aged
      60 and over were protected against diphtheria and tetanus. Two increases of
      diphtheria antitoxin levels greater than 0.1 IU/ml and tetanus antitoxin levels
      greater than 1.0 IU/ml were apparent, starting at 4 and 14 years of age, which
      correspond with the policy of giving a diphtheria and tetanus toxoid booster on
      school entry and a tetanus plus low-dose diphtheria toxoid (recently introduced)
      booster to school leavers. This is the first comprehensive study of diphtheria
      and tetanus immunity in the English and Welsh population and shows that the
      accelerated schedule of immunisation, introduced in 1990, has effectively primed
      immunological memory against both these antigens and that boosting at school
      entry and at school leaving is effective in increasing levels of immunity.

PMID- 10930670
TI  - Safety evaluation of a recombinant myxoma-RHDV virus inducing horizontal
      transmissible protection against myxomatosis and rabbit haemorrhagic disease.
AB  - We have recently developed a transmissible vaccine to immunize rabbits against
      myxomatosis and rabbit haemorrhagic disease based on a recombinant myxoma virus
      (MV) expressing the rabbit haemorrhagic disease virus (RHDV) capsid protein
      [Barcena et al. Horizontal transmissible protection against myxomatosis and
      rabbit haemorragic disease using a recombinant myxoma virus. J. Virol.
      2000;74:1114-23]. Administration of the recombinant virus protects rabbits
      against lethal RHDV and MV challenges. Furthermore, the recombinant virus is
      capable of horizontal spreading promoting protection of contact animals, thus
      providing the opportunity to immunize wild rabbit populations. However, potential
      risks must be extensively evaluated before considering its field use. In this
      study several safety issues concerning the proposed vaccine have been evaluated
      under laboratory conditions. Results indicated that vaccine administration is
      safe even at a 100-fold overdose. No undesirable effects were detected upon
      administration to immunosuppressed or pregnant rabbits. The recombinant virus
      maintained its attenuated phenotype after 10 passages in vivo.

PMID- 10930671
TI  - Seroepidemiology of varicella-zoster virus infection in Catalonia (Spain).
      Rationale for universal vaccination programmes.
AB  - With the aim of designing a strategy for vaccination against varicella-zoster
      virus (VZV), the results of a seroepidemiological survey on VZV infection carried
      out in a sample of the population of Catalonia are presented. Representative
      samples from schoolchildren (30 schools) and adults (97 municipal areas) were
      obtained by random cluster sampling. In the study, 883 children and 1253 adults
      were included. Age, gender, place of birth, place of residence, educational level
      and occupation were investigated in the study subjects. An ELISA test was used to
      measure varicella antibodies. The prevalence of varicella antibodies increased
      with age, being 85% in the 5-9 years age group, 92% in the 10-14 years age group,
      94% in the 15-34 years age group and almost 100% in people over 35. No
      association was found between sociodemographic variables studied and prevalence
      levels of antibodies. These results suggest that the best vaccination strategy in
      Catalonia would be to add a temporary vaccination programme of pre-adolescents at
      12 years to routine vaccination at 15 months.

PMID- 10930672
TI  - Lactogenic immunity following vaccination of cattle with bovine coronavirus.
AB  - In order to investigate the ability of an oil adjuvanted vaccine containing
      bovine coronavirus antigen to enhance lactogenic immunity in the calf, pregnant
      cows and heifers were vaccinated and specific virus neutralising antibody levels
      determined in serum, colostrum and milk. Pre-existing antibody titres (as a
      result of natural infection) in the serum of these animals were found to be
      significantly increased as a result of a single shot vaccination carried out
      between 2 and 12 weeks before calving. This was reflected in a similar increase
      in the titre and duration of specific antibody in milk and colostrum that was
      passed on to the calves. The overall response observed was highly dependent on an
      adequate antigen payload being incorporated within the single dose vaccine. No
      abnormal local or systemic reactions were observed as a result of vaccination. It
      is hoped that this approach will lead to the production of a superior commercial
      vaccine for the protection of neonatal calves against enteric coronavirus
      infection.

PMID- 10930673
TI  - Immunity to diphtheria among children in Northern Norway and North-Western
      Russia.
AB  - In 1990, diphtheria re-emerged in Russia and during the following four-year
      period the resulting epidemic reached all the Newly Independent States (NIS) of
      the former Soviet Union. Several neighbouring countries of NIS, Norway included,
      have experienced sporadic imported cases. A sero-epidemiological study among
      children in Northern Norway and North-Western Russia was performed in order to
      evaluate protection against diphtheria and how differences in vaccination
      programmes affect immunity. A total of 664 sera, 400 from Norwegian and 264 from
      Russian children, were examined for antibodies against diphtheria, using an in
      vitro toxin neutralisation method. The Russian children studied had satisfactory
      protection in all age groups examined. The Norwegian children had poor protection
      against diphtheria from the age of 7 years until they received the booster dose
      at the age of 11. Therefore, a revision of the Norwegian vaccination programme,
      including a booster dose at school-entry age, seems warranted.

PMID- 10930674
TI  - Identification of a major B-cell epitope of the Plasmodium falciparum glutamate
      rich protein (GLURP), targeted by human antibodies mediating parasite killing.
AB  - The antigenicity of the glutamate-rich protein (GLURP) of Plasmodium falciparum
      was comprehensively evaluated in epitope-mapping studies utilizing a phage
      display library, synthetic peptides and anti-GLURP IgG preparations previously
      shown to promote strong antibody-dependent cellular inhibition (ADCI) effects. We
      identified six major B-cell epitopes within the nonrepetitive region R0,
      corresponding to amino acid residues 173 to 187 (P1), 193 to 207 (P3), 216 to 229
      (P4), 264 to 288 (P11), 343 to 357 (P10), and 407 to 434 (S3). Of these, four
      (P1, P3, P4, and S3) were frequently recognized by high-titered IgG antibodies in
      plasma samples from immune Liberian adults (prevalence: 29.1-45.0%). The three
      epitopes P1, P3, and P4 contained a common motif (seven out of nine positions are
      identical) and may thus constitute a family of structurally related epitopes.
      This leaves two distinct epitopes, one (P3) representing this new epitope family
      and S3 as targets for biologically active antibodies. Human IgG antibodies from
      single plasma samples were affinity-purified against these peptides. P3-specific
      IgG preparations were consistently more effective in ADCI than S3-specific IgG.
      Among the different GLURP epitopes, we therefore suggest that the P3 epitope is
      potentially the most important epitope in GLURP for the development of clinical
      immunity to malaria in man.

PMID- 10930675
TI  - Anthrax vaccine: increasing intervals between the first two doses enhances
      antibody response in humans.
AB  - The influence of dosing interval on the human antibody response to anthrax
      vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In
      both studies, the interval between the first two doses was 2, 3 or 4 weeks. In
      the first study, banked sera were selected from 89 at-risk individuals at a mean
      time of 13 days after the second dose of vaccine. In the second study, banked
      sera were selected from 51 at-risk individuals at a mean time of 48 days
      following the first dose of AVA. In both studies, the geometric mean anti
      protective antigen IgG antibody titer increased significantly as the interval
      between the two doses increased from 2 to 4 weeks (p=0.0005-0.029). In the first
      study, the seroconversion rate also increased as the interval between the first
      two doses increased (p=0. 0034). A prospective, randomized study has been
      completed and is being analyzed to confirm these findings.

PMID- 10930676
TI  - Safety and immunogenicity of adjuvanted and unadjuvanted subunit influenza
      vaccines administered intranasally to healthy adults.
AB  - Antigen-specific mucosal immunity is thought to be important for protection
      against influenza virus infection. Currently licensed parenteral influenza
      vaccines stimulate the production of serum antibodies, but are poor inducers of
      mucosal immunity. The adjuvant MF59 has been shown to enhance the humoral immune
      response to parenteral influenza vaccine in humans and the mucosal immune
      response to intranasally-administered influenza vaccine in mice. We conducted an
      open-label safety study followed by an observer-blind, randomized trial comparing
      the immune response to intranasally-administered subunit influenza vaccine
      adjuvanted with MF59, unadjuvanted subunit influenza vaccine, and placebo.
      Adverse reactions did not occur significantly more frequently in vaccinees than
      placebo recipients. Of 31 subjects receiving 2 doses of MF59-adjuvanted influenza
      vaccine, 19 (61%), 8 (26%), and 11 (35%) developed a mucosal IgA response to
      influenza A/H1N1, A/H3N2, and B, respectively. The percentage of subjects with a
      serum antibody response was slightly lower. The immune responses to adjuvanted
      vaccine were not significantly different from those to unadjuvanted vaccine. Both
      vaccines gave more frequent responses than seen in placebo recipients, indicating
      the potential of intranasal inactivated vaccines to stimulate local IgA
      responses.

PMID- 10930677
TI  - Induction of an HPV 6bL1-specific mucosal IgA response by DNA immunization.
AB  - Human papillomavirus (HPV) plays a crucial role in the development of human
      anogenital dysplasia. To prevent infection, it is important to induce an HPV
      specific mucosal immune response. We investigated whether DNA vaccination would
      induce an intravaginal mucosal antibody response against HPV 6bL1. New Zealand
      White rabbits were immunized with an HPV 6bL1 DNA vaccine by one of the three
      routes: muscular, vaginal, or rectal. We found that vaginal immunization of
      rabbits with HPV 6bL1 DNA induced 6bL1 virus-like particle-specific lgA
      antibodies in vaginal secretions. They were detectable until at least 14 weeks
      after the first immunization. The antibodies also showed neutralizing activity in
      a hemagglutination inhibition assay. No mucosal immune response was detected in
      vaginal secretions of rabbits immunized intramuscularly or intrarectally. Our
      data suggest that vaginal immunization with HPV 6bL1 DNA induces long-lasting IgA
      responses with neutralizing activity in vaginal secretions of rabbits.

PMID- 10930678
TI  - CpG DNA as a Th1-promoting adjuvant in immunization against Trypanosoma cruzi.
AB  - Th1-type immune response plays a critical role in resistance to Trypanosoma cruzi
      infection. We asked whether a synthetic oligodeoxynucleotide that contains
      immunostimulatory CpG motifs (CpG ODN), known to promote a Th1 response, could
      act as an adjuvant in immunization with parasite antigens. Mice immunized with a
      whole homogenate (WH) of T. cruzi antigens co-administered with CpG ODN presented
      high titers of T. cruzi antibodies (IgG2a isotype), strong delayed type
      hypersensitivity and a Th1-dominated (IFN-gamma and IL-12) cytokine profile.
      Furthermore, WH plus CpG ODN protected mice from challenge with an otherwise
      lethal dose of bloodstream trypomastigotes. As reported for leishmaniasis and
      malaria, CpG ODN holds considerable promise as an adjuvant for future vaccines
      against T. cruzi.

PMID- 10930679
TI  - A DNA vaccine encoding a conserved Eimeria protein induces protective immunity
      against live Eimeria acervulina challenge.
AB  - Coccidiosis is caused by several distinct intestinal protozoa of Eimeria sp., and
      is responsible for intestinal lesions and severe body weight loss in chickens. To
      develop a DNA vaccination strategy for coccidiosis, an expression vector pMP13
      encoding a conserved antigen of Eimeria was constructed by subcloning 3-1E cDNA
      into pBK-CMV and used to elicit protective immunity against E. acervulina. One
      day-old chickens were immunized intramuscularly (IM) or subcutaneously (SC) with
      various doses of pMP13 expression vector ranging from 5 to 100 ug two weeks apart
      and were challenged with 5x10(3) E. acervulina. Chickens immunized with 5, 10, 50
      or 100 ug of pMP13 plasmid, but not control plasmid, pBK-CMV, showed
      significantly reduced oocysts following challenge infection with E. acervulina.
      Two injections were in general more effective than one injection with higher dose
      of DNA eliciting better protection. At 10 days post challenge infection, maximum
      levels of circulating antibodies were detected regardless of the routes of
      injection, although IM injection provided higher levels of serum antibodies
      compared to SC injection. Serum antibody levels demonstrated a dose-dependent
      response showing higher antibody production at higher DNA dose. DNA immunization
      with pMP13 also induced significant changes in T-cell subpopulations in the
      spleen and duodenum intraepithelial lymphocytes. At 4 days post DNA immunization,
      pMP13-immunized chickens showed lower CD8, and higher CD4(+) and gammadelta T(+)
      cells in the duodenum compared to the pBK-CMV-immunized chickens. Following
      challenge infection with E. acervulina, pMP13-immunized chickens showed lower
      CD8(+) and alphabeta T(+) cells, and higher CD4(+) cells than pBK-CMV-immunized
      chickens in the duodenum. These findings demonstrate that DNA immunization with
      pMP13 induce local and systemic host immune responses against Eimeria.

PMID- 10930681
TI  - Bovine viral diarrhea virus types 1 and 2 antibody response in calves receiving
      modified live virus or inactivated vaccines.
AB  - Serums from calves receiving eight different commercial vaccines containing
      modified live virus (MLV) or inactivated bovine viral diarrhea virus (BVDV)
      immunogens were assayed for antibodies to types 1 and 2 BVDV strains. The immune
      response to the types 1 and 2 BVDV strains were evaluated in 48 calves receiving
      one of the eight vaccines for each group. For 7/8 vaccines, the BVDV vaccine
      immunogen was only type 1 whereas the remaining vaccine contained both types 1
      and 2 immunogens. Calves administered MLV vaccine received only one dose at day
      0, whereas those calves receiving the inactivated vaccines were administered two
      doses initially at days 0 and 28. Selected calves were revaccinated with only one
      dose at day 140. Animals vaccinated with type 1 vaccines developed titers to a
      broad range of type 1 BVDV, both cytopathic (CP) and noncytopathic (NCP)
      biotypes, with lower titers evident to type 2 BVDV strains. For some animals, the
      BVDV serum antibodies did not persist. Revaccination at day 140 induced a
      significant four-fold increase in animals with intermediate to low antibody
      titers. There did not appear to be any clear differences in antibody responses
      between type 1 MLV or inactivated vaccines. The calves receiving the inactivated
      vaccine containing types 1 and 2 had similar antibody levels to both types.

PMID- 10930680
TI  - Immunization with DNA, adenovirus or both in biodegradable alginate microspheres:
      effect of route of inoculation on immune response.
AB  - To determine the potential for biodegradable alginate microspheres to be used as
      a delivery vehicle for DNA based vaccines, we constructed a plasmid, pMNe-gal
      SV40, containing the bacterial beta-galactosidase (LacZ) gene under the control
      of the murine cytomegalovirus (MCMV) immediate-early promoter and the simian
      virus 40 (SV40) polyadenylation signal. The effect of the route of administration
      and co-administration of adenovirus on systemic and mucosal immune responses were
      investigated. Mice were inoculated orally, intranasally (i.n.), intramuscularly
      (i.m.), subcutaneously (s.c.) or intraperitoneally (i.p.) on days 0, 14 and 28
      with microspheres containing plasmid DNA, bovine adenovirus type 3 (BAd3) or
      plasmid DNA + BAd3. Systemic routes of immunization (i.m., s.c. and i.p.)
      resulted in higher LacZ- or BAd3-specific IgG ELISA titers compared to those
      obtained by mucosal routes of inoculation (oral and i.n.). Mucosal immunization
      led to slightly higher titers of LacZ- or BAd3-specific IgA at mucosal sites
      compared to those obtained by the various systemic routes. All the routes of
      immunization induced LacZ-specific lymphoproliferation. Co-administration of BAd3
      enhanced the LacZ-specific IgG response irrespective of the route of
      administration.

PMID- 10930682
TI  - Aluminium phosphate adjuvants prepared by precipitation at constant pH. Part I:
      composition and structure.
AB  - Aluminium phosphate adjuvant was precipitated under constant pH conditions in an
      effort to characterize materials formed at defined precipitation conditions. A
      reaction vessel was designed to provide a continuous steady-state process. An
      aqueous solution containing aluminium chloride and sodium dihydrogen phosphate
      was pumped into the reaction vessel at a constant rate. A second pump infused a
      sodium hydroxide solution at the rate required to maintain the desired pH.
      Precipitations were performed between pH 3.0 and 7.5, at intervals of pH 0.5. The
      adjuvants were characterized using 27Al NMR, FTIR, Raman and X-ray diffraction
      methods along with elemental analysis. The results of this study indicate that a
      continuum of amorphous aluminium hydroxyphosphates were formed having properties
      that changed as a continuous function of the precipitation pH. The phosphate
      content decreased as the pH of precipitation increased. 27Al NMR spectra revealed
      that the majority of the aluminium was octahedrally coordinated, with a small
      percentage of tetrahedrally coordinated aluminium. The density of the adjuvants
      was directly related to the pH of precipitation. The most prominent feature of
      the IR and Raman spectra is the P-O stretching vibration of the structural PO(4)
      groups. The positions of these bands decreased linearly as the precipitation pH
      increased. The results of selective deuteration FTIR experiments are consistent
      with high surface area materials as most of the OH groups were exposed near the
      surface of the adjuvant.

PMID- 10930683
TI  - Aluminium phosphate adjuvants prepared by precipitation at constant pH. Part II:
      physicochemical properties.
AB  - The impact of the pH of precipitation on the physicochemical properties of
      aluminium phosphate adjuvants was investigated by precipitating aluminium
      phosphate adjuvants under constant pH conditions at pH values from 3.0 to 7.5 at
      intervals of 0.5. The pH of precipitation did not affect the morphology, but the
      point of zero charge (PZC) and rate of acid neutralization varied directly with
      pH of precipitation. Aggregation and protein adsorption capacity exhibited a
      parabolic relationship to the pH of precipitation. Minimum protein adsorption and
      maximum aggregation were observed at pH 5.5. In contrast to adjuvants
      precipitated from the same reactants but under uncontrolled pH conditions, the pH
      of all of the adjuvants precipitated under constant pH conditions remained
      constant for a 3-month aging period at room temperature.

PMID- 10930685
TI  - Cell-mediated immunity to low doses of SIVsm in cynomolgus macaques did not
      confer protection against mucosal rechallenge.
AB  - Simian immunodeficiency virus (SIV) infection of macaques is a useful model for
      studies of the roles of different immune responses against viruses that cause
      (AIDS). In this study, six cynomolgus macaques were inoculated intrarectally with
      subinfectious or infectious doses of SIVsm to assess the SIV specific immunity,
      in particular protective immunity against subsequent challenge with a higher dose
      of SIVsm. Following the first inoculation with SIVsm, the two monkeys given the
      highest doses of cell-free SIVsm stock and one monkey given the intermediate dose
      became infected. In the three remaining animals, one animal inoculated with an
      intermediate dose and two animals given low doses of SIVsm, no overt infection
      occurred. Nevertheless, SIV specific cytotoxic T-cells against Gag/Pol and Nef
      proteins and T-cell proliferative responses against HIV-2 whole viral lysate,
      native HIV-2 gp125, recombinant SIV gp140 and SIV Env synthetic peptides were
      detected. After intrarectal rechallenge of the uninfected macaques with a higher
      dose of SIVsm all the animals became infected. These results demonstrate that
      cell mediated immunity can occur in the absence of detectable infection in
      monkeys inoculated with a low dose of SIVsm. Despite the presence of cellular
      immune responses, the animals were not protected when challenged with a higher
      dose of virus later.

PMID- 10930684
TI  - Cloning, expression and evaluation of a recombinant sub-unit vaccine against
      Clostridium botulinum type F toxin.
AB  - A synthetic gene encoding the Hc (binding) domain of Clostridium botulinum
      neurotoxin F (FHc) was expressed in Escherichia coli fused to maltose binding
      protein (MBP). The purified MBP-FHc and FHc isolated after removal of MBP were
      evaluated in mice for their ability to protect against toxin challenge. Balb/c
      mice developed a protective immune response following administration of either
      protein via the intraperitoneal or intramuscular routes. A comparison of antibody
      titres and protection following single and multiple vaccinations and the effects
      of dosage are shown. The long term protection afforded by the vaccines was also
      investigated. Ten months following vaccination mice were still protected when
      challenged with 10(4) MLD(50) doses of botulinum toxin F.

PMID- 10930686
TI  - Immunogenicity and efficacy of Russian live attenuated and US inactivated
      influenza vaccines used alone and in combination in nursing home residents.
AB  - The immunogenicity and efficacy of Russian live attenuated and US inactivated
      trivalent influenza vaccines administered alone or in three different
      combinations were evaluated in a randomized, placebo-controlled, double-blinded
      study of 614 elderly or chronically ill nursing home residents in St. Petersburg,
      Russia during the 1996-97 influenza season. Postvaccination serum antibody
      responses were more frequent among individuals administered the combination
      vaccines than among those vaccinated with live or inactivated vaccine alone. Only
      individuals who received live vaccine, alone or in combination with inactivated
      vaccine, achieved significant postvaccination increases in virus-specific nasal
      IgA. Efficacy in preventing laboratory-confirmed influenza in vaccinated versus
      nonvaccinated individuals was 67% (95%CI, 36-81%) for recipients of a combination
      of the vaccines compared with 51% (95%CI, -17-79%) for recipients of live vaccine
      alone and 50% (95%CI, -26-80%) for recipients of inactivated vaccine alone. These
      results suggest that administration of a combination of influenza vaccines may
      provide a strategy for improved influenza vaccination of elderly people.

PMID- 10930687
TI  - Intent-to-treat analysis and preventive vaccine efficacy.
AB  - While the intent-to-treat (ITT) concept has often been discussed and debated in
      the literature with respect to randomized, placebo-controlled therapeutic trials,
      there has been little discussion of this issue in the context of preventive
      vaccine efficacy trials. ITT analysis has traditionally played a minor role (if
      any) in the latter trials. This paper discusses the ITT approach to analysis in
      randomized superiority trials of preventive vaccine efficacy, using clinical
      endpoints. Data are presented from published literature as well as from a simple
      mathematical model. The data suggest that when compliance and efficacy are high,
      both ITT and "per-protocol" approaches generally lead to similar conclusions
      regarding the acceptability of a vaccine for use in a population. However, when
      compliance is low, the ITT and per-protocol estimates of vaccine efficacy can be
      widely disparate. ITT and per-protocol analyses address unique and relevant
      scientific questions, and often both will be informative in evaluating preventive
      vaccines.

PMID- 10930688
TI  - Recombinant modified vaccinia virus Ankara efficiently restimulates human
      cytotoxic T lymphocytes in vitro.
AB  - The immunogenicity of recombinant modified vaccinia Ankara, a highly attenuated
      vaccinia virus, expressing influenza nucleoprotein (MVA-NP) and HIV-1 gag (MVA
      gag) was investigated. Restimulation of peripheral blood lymphocytes of healthy
      subjects with MVA-NP led to expansion of CTL with specificity for known NP
      epitopes. These CTL efficiently lysed NP peptide-pulsed targets and released
      interferon-gamma (IFN-gamma) on contact with epitope peptide. MVA-NP-stimulated
      CTL specific for the HLA-B8 epitope, NP380-88, stained with a tetrameric complex
      of HLA-B8 refolded with the NP380-88 peptide and anti-CD8 antibody on flow
      cytometry. CTL were also elicited from two HIV-1 seropositive donors by
      restimulation with MVA-HIV-1 gag and showed specificity for immunodominant gag
      epitopes. These data indicate that restimulation of human CTL with recombinant
      MVA is effective and suggest that MVA will elicit CTL responses in humans in
      vivo.

PMID- 10930689
TI  - An immunological profile of Balb/c mice protected from airborne challenge
      following vaccination with a live attenuated Venezuelan equine encephalitis virus
      vaccine.
AB  - The live attenuated vaccine strain of Venezuelan equine encephalitis virus
      (VEEV), TC-83, protects mice against challenge (subcutaneous and aerosol) with
      virulent VEEV but is not suitable for widescale human use. Elucidation of the
      immune response profile of protected mice should assist in the development of an
      improved vaccine. We determined the optimum dose of TC-83 required to
      consistently protect Balb/c mice from airborne challenge with the virulent
      Trinidad Donkey strain of VEEV and studied the development of humoral and
      cellular immune responses in protected mice between 6 h and 21 days post
      vaccination. The most dramatic immune responses occurred in draining lymph nodes
      24 h following vaccination with increased levels of activated B cells and T cells
      of both CD4(+) and CD8(+) subtypes. Activated monocyte/macrophages and natural
      killer cells were also seen between 6 h and 7 days post-vaccination. Serum
      contained detectable VEEV-specific IgG on day 5 post-vaccination with titres
      continuing to rise on days 7, 14 and 21. Isotypes of IgG measured on days 7 and
      21 were predominantly of the IgG2a subclass, indicating that the immune response
      was Th1-mediated. Cytokine mRNA was quantified by RT-PCR and revealed production
      of the Th1 cytokine IFN-gamma and the inflammatory cytokine TNF-alpha, whereas
      the Th2 cytokine IL4 was not detected above control levels at any of the time
      points studied. This data describes key cellular immune responses at early times
      post-vaccination and is consistent with previous data demonstrating protection
      against aerosol challenge with VEEV in the absence of detectable levels of
      specific IgG or IgA antibody.

PMID- 10930690
TI  - Catalase immunization from Pseudomonas aeruginosa enhances bacterial clearance in
      the rat lung.
AB  - Pseudomonas aeruginosa is a common cause of infection in immunocompromised
      patients and is the major contributor to morbidity in individuals with cystic
      fibrosis (CF). The antibiotic resistance shown by this pathogen and morbidity in
      patients with chronic infection has encouraged investigations into the
      development of a vaccine. This study reports the purification of a 60 kDa
      protein, isolated from a mucoid strain of P. aeruginosa, identified by amino acid
      sequence analysis as the catalase protein (KatA). A rat model of acute P.
      aeruginosa respiratory infection was used to investigate the immunogenicity of
      KatA and determine the potential of mucosal immunization with KatA to protect
      against infection. Immunization regimens compared a single intra-Peyer's patch
      (IPP) immunization with an IPP primary inoculation followed by an intratracheal
      boost to the lungs. Mucosal immunization with KatA resulted in significant
      pulmonary clearance of both homologous (p<0.001) and heterologous (p<0.05)
      strains of P. aeruginosa. Both immunization regimens enhanced bacterial
      clearance, increased the rate of recruitment of phagocytes to the bronchoalveoli
      and induced KatA-specific antibody. However, the regimen that included a boost
      induced a more effective immune response that also resulted in better clearance
      of P. aeruginosa from the lungs. Mucosal immunization induced KatA- specific
      antibodies in the serum and the bronchoalveolar lavage, and KatA-specific
      lymphocyte proliferation in vitro in cells isolated from the mesenteric lymph
      nodes of immunized rats. The data presented suggests that KatA has the potential
      to afford a protective immune response against pulmonary infection by P.
      aeruginosa

PMID- 10930691
TI  - Protection conferred by a fully recombinant sub-unit vaccine against Yersinia
      pestis in male and female mice of four inbred strains.
AB  - In this paper, we describe for the first time the use of a fully recombinant sub
      unit vaccine for plague. We have compared the protection afforded by the
      recombinant vaccine against Yersinia pestis in male and female mice of four
      inbred strains. We also determined the in vivo cellular memory and antibody
      response after one year. The recombinant vaccine was capable of inducing
      protective immunity, against subcutaneous and aerosol challenge, in mice from all
      four strains. Although, there was some breakthrough in the CBA males challenged
      with 10(7) median lethal dose (MLDs) the other mice regardless of sex or strain
      were well protected even at this extreme challenge dose. In both male and female
      mice, the specific IgG titres to both antigens peaked at day 28 and 35 and in
      female mice these titres were maintained for >1 year.

PMID- 10930692
TI  - Associated or combined vaccination of Brazilian infants with a conjugate
      Haemophilus influenzae type b (Hib) vaccine, a diphtheria-tetanus-whole-cell
      pertussis vaccine and IPV or OPV elicits protective levels of antibodies against
      Hib.
AB  - This study investigated the immunogenicity and safety of including a Haemophilus
      influenzae type b vaccine (polyribosylribitol phosphate conjugated to tetanus
      toxoid, PRP-T) in three different vaccination schemes: (1) PRP-T reconstituted
      with a combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccine (DTP
      IPV//PRP-T); (2) PRP-T reconstituted with DTP and administered concomitantly with
      an oral poliovirus vaccine (DTP//PRP-T+OPV); and (3) PRP-T administered
      concomitantly with DTP at a different injection site and OPV (DTP+PRP-T+OPV).
      Vaccines were given at 2, 4, and 6 months of age. A total of 252 infants were
      enrolled, and randomly assigned to one of the three vaccination groups (84
      infants in each group); 241 infants were followed until the end of the study.
      Antibody production against PRP, diphtheria, tetanus and pertussis antigens was
      satisfactory for each vaccination scheme used. A good response to Hib vaccine was
      elicited in each group, and 3 months after the third vaccine dose, at least 97%
      of children in each group had levels of PRP antibody considered to be
      seroprotective (>0.15 microg/ml), and over 90% of children in each group had
      levels over 1. 0 microg/ml. The solicited local and systemic adverse events
      following vaccination were mild in all groups and resolved within 4 days without
      medical intervention. With the exception of fever, which was more common after
      the second dose in children who received DTP-IPV//PRP-T, local and systemic
      reactions did not differ between the vaccination groups. Due to the practical
      advantages of combined vaccines, their use in routine immunization programs in
      developing countries is highly desirable. Our results show that Hib conjugate
      vaccine can be included in routine immunization programs that include either OPV
      or IPV with satisfactory immunogenicity and safety profiles. This flexible
      approach should facilitate the inclusion of the Hib conjugate vaccine in routine
      immunization programs on a world-wide scale.

PMID- 10930693
TI  - Passive protection of serum from volunteers inoculated with attenuated strain 638
      of Vibrio cholerae O1 in animal models.
AB  - As part of the studies to obtain an oral vaccine against cholera disease, the
      protective effect of serum from volunteers inoculated in a controlled trial with
      a candidate live attenuated vaccine of Vibrio cholerae O1, El Tor Ogawa (638;
      CTX&phi; mutant, hap::celA), was tested. It was confirmed that the serum, as well
      as the purified IgG and IgA from the volunteers had a protective effect in both
      of the animal models used, although the purified antibodies needed the presence
      of complement to be protective. These results emphasize the expectations about
      the protective potential of the candidate in challenge studies in humans to be
      conducted very soon.

PMID- 10930694
TI  - Biotransformation of the citrus flavone tangeretin in rats. Identification of
      metabolites with intact flavane nucleus.
AB  - The present study was carried out in order to investigate the in vivo
      biotransformation and excretion of the flavone, tangeretin, found in citrus
      fruits, by analysing urine and faeces samples from rats after repeated
      administration of 100 mg/kg body weight/day tangeretin. The formed metabolites
      were separated and identified by HPLC and the structures elucidated by LC/MS and
      1H NMR. Ten new, major metabolites with intact flavonoid structure were
      identified. The metabolites identified were either demethylated or hydroxylated
      derivatives of the parent compound and metabolic changes were found primarily to
      occur in the 4' position of the B-ring. The total urinary excretion of tangeretin
      metabolites with intact flavan nucleus was about 11% of the administered daily
      dose.

PMID- 10930695
TI  - Protective effect of extracts of Mesona procumbens Hemsl. on DNA damage in human
      lymphocytes exposed to hydrogen peroxide and UV irradiation.
AB  - In the present study, the protective effect of water extracts from Hsian-tsao
      (WEHT) on DNA damage in human lymphocytes induced by UV-C and/or H(2)O(2) was
      evaluated using single-cell electrophoresis (comet assay). No toxicity was found
      in WEHT towards human lymphocytes. WEHT did not cause DNA damage at lower
      concentrations of 0.05 and 0.1 mg/ml, while it did cause slight DNA damage at a
      concentration of 0.5-2.5 mg/ml when compared with the control group. When WEHT
      was mixed with H(2)O(2) for reaction, it exhibited a slight inhibitory effect on
      DNA damage induced by H(2)O(2). Moreover, when WEHT and lymphocytes were
      irradiated by UV-C and then incubated for 35 min, the DNA damage decreased with
      an increase of the concentration of WEHT. Thus, WEHT could reduce UV-C-induced
      DNA damage, and WEHT had a more protective effect on UV-C than on H(2)O(2)
      induced DNA damage. The protective effect of WEHT on DNA damage might be due to
      the fact that it contains polyphenol compounds and/or other active components.

PMID- 10930696
TI  - Effect of cinnamon, clove and some of their constituents on the Na(+)-K(+)-ATPase
      activity and alanine absorption in the rat jejunum.
AB  - The effect of a water extract of some spices on the in vitro activity of the rat
      jejunal Na(+)-K(+)-ATPase was investigated. Extracts of nutmeg, cinnamon, clove,
      cumin, coriander, turmeric and caraway all inhibited the ATPase, while anise seed
      and white pepper exerted no significant effects. The extracts of clove and
      cinnamon had the most potent inhibitory effect on the intestinal ATPase as
      compared to extracts of other spices. They also inhibited the in vitro Na(+)-K(+)
      ATPase activity in a crude kidney homogenate and the activity of an isolated dog
      kidney Na(+)-K(+)-ATPase. The alcoholic extract of cinnamon, compared to the
      aqueous extract, had a stronger inhibitory action on the jejunal enzyme and a
      lower IC(50) value, which was not significantly different from the one observed
      with cinnamaldehyde, the major volatile oil present cinnamon, suggesting that in
      alcoholic extracts cinnamaldehyde is the major inhibitory component. The IC(50)
      values of eugenol, aqueous clove extract and ethanolic clove extract all fell
      within the same range and were not significantly different from each other,
      suggesting that eugenol is the major inhibitory component in both alcoholic and
      aqueous extracts. Based on the IC(50) values, the order of sensitivity of the
      enzyme to the spices extracts is as follows: isolated dog kidney ATPase>rat
      kidney ATPase>rat intestine ATPase. The aqueous extracts of clove and cinnamon
      also significantly lowered the absorption of alanine from the rat intestine. It
      was concluded that the active principle(s) in clove and cinnamon can permeate the
      membrane of the enterocytes and inhibit the Na(+)-K(+)-ATPase that provides the
      driving force for many transport processes.

PMID- 10930697
TI  - A developmental safety study in rats using DHA- and ARA-rich single-cell oils.
AB  - The long-chain omega-3 and omega-6 fatty acids, docosahexaenoic and arachidonic
      acids, are important in fetal development, but may be depleted from the mother
      during pregnancy as she transfers reserves to the developing fetus in utero and
      later to the infant through her breast milk. Pregnant women can increase their
      dietary intake of these nutrients to maintain adequate maternal reserves and
      ensure an optimal infant supply. DHASCO(R) and ARASCO(R) oils, concentrated
      sources of docosahexaenoic and arachidonic acids, respectively, have been tested
      in acute and subchronic studies without toxic effects. The present developmental
      toxicity study was undertaken to test for potential teratogenic activity of these
      oils to ensure their safe use during pregnancy. DHASCO and ARASCO oils were
      administered by oral gavage to pregnant rats at doses up to 1250 and 2500 mg/kg
      body weight/day, respectively, during the period of organogenesis. Caesarean
      sections and necropsies were performed on day 20 of gestation. Maternal
      reproductive outcomes were analyzed, and fetal external, soft and skeletal tissue
      were examined. Treatment with these oils did not produce overt maternal toxicity,
      nor did either oil result in changes in pre- or postimplantation losses,
      resorptions, live births or sex ratios. Neither oil caused fetal malformations.
      Increased frequencies of renal variations in development occurred in a non-dose
      dependent manner and were not toxicologically significant. We conclude that these
      oils are not teratogenic at doses that represent a 100-fold safety factor over
      expected use levels.

PMID- 10930698
TI  - Studies on the carcinogenicity of potassium iodide in F344 rats.
AB  - A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj
      rats were given potassium iodide (KI) in the drinking water at concentrations of
      0, 10, 100 or 1000 ppm for 104 weeks, and a two-stage carcinogenicity study of
      application at 0 or 1000 ppm for 83 weeks following a single injection of N-bis(2
      hydroxypropyl)nitrosamine (DHPN), were conducted. In the former, squamous cell
      carcinomas were induced in the salivary glands of the 1000 ppm group, but no
      tumors were observed in the thyroid. In the two-stage carcinogenicity study,
      thyroidal weights and the incidence of thyroid tumors derived from the follicular
      epithelium were significantly increased in the DHPN+KI as compared with the DHPN
      alone group. The results of our studies suggest that excess KI has a thyroid
      tumor-promoting effect, but KI per se does not induce thyroid tumors in rats. In
      the salivary gland, KI was suggested to have carcinogenic potential via an
      epigenetic mechanism, only active at a high dose.

PMID- 10930699
TI  - Application of a dynamic in vitro gastrointestinal tract model to study the
      availability of food mutagens, using heterocyclic aromatic amines as model
      compounds.
AB  - The TNO gastro-Intestinal tract Model (TIM) is a dynamic computer-controlled in
      vitro system that mimics the human physiological conditions in the stomach and
      small intestine. In the current TIM physiological parameters such as pH,
      temperature, peristaltic movements, secretion of digestion enzymes, bile and
      pancreatic juices, and absorption of digested products-by removal through
      dialysis-was simulated. Heterocyclic aromatic amines (HAA; viz. IQ, MeIQ, MeIQx
      and PhIP) were used as model compounds for food mutagens, and the passage through
      TIM was investigated for each of these compounds separately. Subsequently, the
      influence of a matrix and different rates of passage on the availability for
      absorption and distribution were studied in experiments with prepared meat,
      supplemented with MeIQx. Samples taken at various time points from the jejunal
      and ileal dialysates and from the lumen at the end of the small intestine (ileal
      delivery) were tested for the presence of mutagenic activity in the Ames test
      with Salmonella typhimurium strain TA98 as indicator, in the presence of
      mammalian metabolic activation (rat S9 mix). The results show that, comparable
      with the human in vivo situation, all four HAA are quickly removed (approx. 50%
      in 2 hr; approx. 95% in 6 hr) and mainly recovered from the lumen into the
      jejunal and ileal dialysates (94% of recovery). Only 5+/-1.5% is recovered in the
      chyme at the end of the small intestine. When MeIQx was added to meat, its
      availability for absorption was slower, although the influence of the
      gastrointestinal passage time on the availability of MeIQx was more pronounced
      than this matrix effect. More MeIQx was found in the jejunal dialysate (23%;
      P<0.01) and less in the ileal delivery (8%; P<0.01) when simulating the
      gastrointestinal passage of solid meals was compared to simulating that of liquid
      meals. The present experiments demonstrate that TIM can be applied to study in
      vitro the availability of heterocyclic aromatic amines in the gastrointestinal
      tract. More generally, these studies indicate that TIM shows promise as a useful
      tool for various research purposes dealing with the availability for absorption
      of mutagenic as well as antimutagenic components in food.

PMID- 10930700
TI  - Disruption of sphingolipid metabolism in small intestines, liver and kidney of
      mice dosed subcutaneously with fumonisin B(1).
AB  - Fumonisin B(1) is a fungal inhibitor of ceramide synthase, a key enzyme in the de
      novo biosynthesis of sphingolipids. The resulting increase in tissue free
      sphinganine (and sometimes sphingosine) is used as a biomarker for fumonisin
      exposure. This study determined whether a single subcutaneous injection of
      fumonisin B(1) could cause an increase in free sphingoid bases in the intestinal
      epithelial cells of mice over 24 hr. It was hypothesized that fumonisin
      administered subcutaneously would be excreted into the small intestine via
      biliary excretion, and this should be detectable by increased sphingoid bases in
      the intestine. A significant time-dependent increase in sphingoid bases occurred
      in the intestine and liver peaking at 4-8 hr and declining to control levels by
      24 hr. In the kidney the increase in free sphinganine was persistent. The
      parallel time course of the change in sphinganine in the intestine and liver
      suggested fumonisin B(1) was rapidly excreted into the small intestine. Rapid
      cell turnover in the intestine could account for the reversal of the sphinganine
      increase. The rapid return to the control level in liver was unexpected since
      ceramide synthase inhibition in cultured cells is persistent suggesting that
      liver handles fumonisin B(1) or sphingoid bases quite differently than kidney.

PMID- 10930701
TI  - 5-Hydroxymethylfurfural: assessment of mutagenicity, DNA-damaging potential and
      reactivity towards cellular glutathione.
AB  - 5-(hydroxymethyl)-2-furfural (HMF), a common product of the Maillard reaction,
      occurs in many foods in high concentrations, sometimes exceeding 1 g/kg (in
      certain dried fruits and caramel products). The toxicological relevance of this
      exposure has not yet been clarified. Induction of aberrant colonic crypt foci had
      been reported for HMF, in vitro studies on genotoxicity/mutagenicity have given
      controversial results. To elucidate the toxic potential of HMF, cytotoxicity
      (trypan blue exclusion), growth inhibition (SRB assay), mutagenicity (HPRT
      assay), DNA damage (single-cell gel electrophoresis) and depletion of cellular
      glutathione were investigated in mammalian cells. Genotoxicity (SOS repair) was
      monitored in Salmonella typhimurium (umu assay). HMF induced moderate
      cytotoxicity in V79 cells (LC(50): 115 mM, 1 hr incubation) and in Caco-2 cells
      (LC(50): 118 mM, 1 hr incubation). Growth inhibition was monitored following 24
      hr of incubation (V79, IC(50): 6.4 mM). DNA damage was detectable neither in
      these cell lines nor in primary rat hepatocytes up to the cytotoxic threshold
      concentration (75% absolute viability). Likewise, in primary human colon cells,
      obtained from biopsy material, DNA damage was not measurable. At 120 mM, already
      exhibiting some reduction in cell viability, HMF was weakly mutagenic at the hprt
      locus in V79 cells (mutants/10(6) cells: HMF 120 mM: 16 vs control: 3).
      Intracelluar glutathione was depleted by HMF (>/=50 mM) in V79 cells, in the
      human colon adenocarcinoma cell line Caco-2 and in primary rat hepatocytes down
      to approximately 30% of control (120 mM). Genotoxicity was observed with HMF in
      the umu assay without external activation (16 mM: 185 rel. umu units, %,
      P<0.001). The genotoxic potential was not altered by addition of rat liver
      microsomes. By comparison, the natural flavour constituent (E)-2-hexenal (HEX)
      was already cytotoxic, mutagenic and depleted glutathione at about 1000-fold
      lower concentrations. It induced DNA damage in mammalian cells (200-400 microM).
      These results suggest that HMF does not pose a serious health risk, even though
      the highest concentrations in specific foods approach the biologically effective
      concentration range in cell systems.

PMID- 10930702
TI  - Thirteen-week dietary intake of rapeseed oil or soybean oil as the only dietary
      fat in Wistar Kyoto rats-change in blood pressure.
AB  - Wistar Kyoto (WKY) rats were fed a diet containing 10% rapeseed (canola) oil or
      soybean oil as the only dietary fat for 13 weeks. From week 5 of feeding,
      systolic blood pressure of the canola oil group became higher than that of the
      soybean oil group. The 13-week canola oil intake increased plasma levels of Na(+)
      and lipids, and decreased the level of K(+) compared to those in the soybean oil
      group. The canola oil group also showed a high density of neutrophils and a low
      density of platelets compared to the soybean oil group. Moreover, the activities
      of catalase and superoxide dismutase in the hepatic cytosol were depressed in the
      canola oil group. The mechanisms for the higher blood pressure are unclear.
      However, an increase in body fluid via activation of Na(+) pump or Na(+), K(+)
      ATPase and/or a blunt endothelium-dependent vasodilation by increased superoxide
      might have relevance to the elevated blood pressure. The increased plasma lipids
      and the changes in the densities of platelets and neutrophils appear not to be
      critical in WKY rats. However, these would tend to promote peripheral vascular
      lesions in the strains, such as spontaneously hypertensive rats and stroke-prone
      spontaneously hypertensive rats, which are prone to present atheroscrelotic
      vascular injury.

PMID- 10930703
TI  - The acute and subchronic toxicity of BRB-I-28, a novel class Ib antiarrhythmic
      agent, in CD-1 mice.
AB  - The acute and subchronic toxic effects of BRB-I-28 (7-benzyl-3-thia-7
      azabicyclo[3.3.1]nonane HCl), a novel class Ib antiarrhythmic agent, were
      investigated in male and female mice. The estimated oral LD(50) for BRB-I-28 was
      128 mg/kg (male mice) and 131 mg/kg (female mice). In subchronic oral studies,
      four groups of mice (15/sex/group/dose) were fed daily with diets containing BRB
      I-28 for 90 consecutive days. The equivalent daily doses were approximately 0,
      16, 32, 76 (male) and 0, 18, 37, 89 mg/kg (female). All mice survived. Food
      consumption per day was decreased, but water consumption per day was increased
      (in a non-dose-dependent manner). However, both mean body weight and mean body
      weight gain were not significantly changed as were true for hematological and
      clinical chemistry profiles, except for serum Na(+) concentration (male) and
      serum K(+) concentration in male and female mice (high dose levels).
      Hepatocellular necrosis occurred in male and female mice (in a dose-dependent
      fashion). Renal cortical vacuoles and myocardial necrosis with low numbers of
      lymphocytic infiltrations were present in female mice (middle and high doses).
      Lesions in the liver, kidney and heart were mild with (very small) changes in
      serum biochemical values. These data suggest that BRB-I-28 has limited toxic
      potential, and coupled with low proarrhythmic and other desirable cardiovascular
      effects, makes BRB-I-28 worthy of further development.

PMID- 10930704
TI  - "IARC group 2B Carcinogens" reported in cigarette mainstream smoke.
AB  - In the third and final part of a series surveying the international literature on
      the "IARC carcinogens" in cigarette mainstream smoke, the "IARC Group 2B
      carcinogens" are reviewed. A search of the published literature shows that of 227
      chemical components classified as Group 2B, that is, "possible carcinogens," by
      the International Agency for Research on Cancer (IARC), 48 have previously been
      reported in cigarette mainstream smoke. Owing to its highly interactive molecular
      nature, removal from or inhibition of a given mutagenic or carcinogenic chemical
      within the complex aerosol mixture cannot reliably be predicted to reduce either
      the overall mutagenicity or carcinogenicity. However, in the absence of
      experimental data demonstrating an increase in adverse biological activity
      resulting from removal or inhibition of a potentially carcinogenic constituent,
      negation of the activity of the potential carcinogen may be considered as a
      desirable circumstance.

PMID- 10930705
TI  - Effect of the natural antioxidant 2"-O-glycosylisovitexin on superoxide and
      hydroxyl radical generation.
AB  - The inhibitory effect of 2"-O-glycosyl isovitexin (2"-O-GIV) isolated from green
      barley leaves on superoxide and hydroxyl radical generation was investigated
      using electron spin resonance spectroscopy. 2"-O-GIV exhibited dose-related
      inhibitory activity both towards superoxide generation and hydroxyl radical
      generation. 2"-O-GIV inhibited superoxide formation by 97% at a level of 25 mM
      and inhibited hydroxyl radical formation by 91% at a level of 500 microM. The
      results suggest that the inhibitory activity of 2"-O-GIV is due to trapping
      radicals.

PMID- 10930706
TI  - The aphrodisiac and adaptogenic properties of ginseng.
AB  - Ginseng is the root of the perennial herbs of Panax quinquefolium and Panax
      ginseng which contain a series of tetracyclic triterpenoid saponins
      (ginsenosides) as active ingredients. It is considered a tonic or adaptogenic
      that enhances physical performance (including sexual), promotes vitality and
      increases resistance to stress and ageing. The adaptogenic properties of ginseng
      are believed to be due to its effects on hypothalamic-pituitary-adrenal axis,
      resulting in elevated plasma corticotropin and corticosteroids levels. When used
      appropriately, ginseng appears to be safe. Nevertheless, documented side effects
      include hypertension, diarrhoea, restlessness, mastalgia and vaginal bleeding.

PMID- 10930707
TI  - Cannabis and cannabinoid receptors.
AB  - Cannabis and cannabinoids exert many of their biological functions through
      receptor-mediated mechanisms. Two types of cannabinoid receptors have been
      identified, namely CB(1) and CB(2), both coupled to a G protein. CB(1) receptors
      have been detected in the central nervous system (where they are responsible for
      the characteristic effects of Cannabis, including catalepsy, depression of motor
      activity, analgesia and feelings of relaxation and well being) and in peripheral
      neurons (where their activation produces a suppression in neurotransmitter
      release in the heart, bladder, intestine and vas deferens). Cannabinoid CB(2)
      receptors have only been detected outside the central nervous system, mostly in
      cells of the immune system, presumably mediating cannabinoid-induced
      immunosuppression and antinflammatory effects. With the discovery of cannabinoid
      receptors for exogenous cannabinoids, also endogenous cannabinoids (anandamide, 2
      arachidonylglycerol) have been described.

PMID- 10930708
TI  - Traditional medicine as a source of new therapeutic agents against psoriasis.
AB  - In the frame of traditional medicine, the use in the treatment of psoriasis of
      some plants typical of the flora of Sicily is reported. A preliminary search on
      some plants used for the treatment of psoriasis in Asia, South America and Africa
      is also reported.

PMID- 10930709
TI  - Botanical derivatives for the prostate.
AB  - The prostate, after the age of 45 years, may undergo benign hyperplasia (BPH).
      Its etiology has not yet been completely explained, but different factors play a
      major role in its occurrence, among them, the sexual hormones (with a fundamental
      role of 5 alpha reductase). The 5-alpha reductase activity and inflammatory
      aspects in the prostate tissue can be effectively controlled with the use of
      highly standardized plant extracts (Pygeum africanum, Serenoa repens, etc.),
      which yield excellent results in the prophylaxis and treatment of the symptoms
      linked to prostate hypertrophy. The prostate tissue is not affected only by
      benign diseases but may also be subject to neoplastic transformation. From an
      epidemiological point of view, a vegetable derivative, lycopene, was linked with
      a lower occurrence of prostate carcinoma. A recent clinical study demonstrated
      that lycopene might not only prevent prostate cancer but also have therapeutic
      effects.

PMID- 10930710
TI  - Grapefruit: the last decade acquisitions.
AB  - This review reports the last decade acquisitions on grapefruit. New coumarins and
      limonoids were isolated and characterised. The bioavailability of many drugs was
      tested with grapefruit juice (GJ) coadministration; the inhibition on cytochrome
      P450 seems due to a synergic action between flavonoids and coumarins.
      Antimicrobial, antifeeding, insecticidal, and antitumour activities were also
      reported.

PMID- 10930711
TI  - Potential use of medicinal plants in the treatment of alcoholism.
AB  - The present paper briefly reviews the most relevant experimental data on the
      reducing effect of some medicinal herbs on voluntary alcohol intake in animal
      models of alcoholism. Pueraria lobata, Tabernanthe iboga, Panax ginseng, Salvia
      miltiorrhiza and Hypericum perforatum proved to be effective in decreasing
      alcohol consumption. Reduction of alcohol absorption from the gastrointestinal
      system appears to be a common feature among most of the above plants. These data
      suggest that medicinal plants may constitute novel and effective
      pharmacotherapies for alcoholism.

PMID- 10930712
TI  - Ginkgo biloba and the central nervous system.
AB  - In this paper the main features of the pharmacological effects exerted by Ginkgo
      biloba leaf extracts on central nervous system functions are reviewed.

PMID- 10930713
TI  - Prostaglandins and nitric oxide as molecular targets for anti-inflammatory
      therapy.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most used drugs
      worldwide, in spite of their renal and gastric side effects. Medicinal plants may
      represent a useful source of new effective therapeutic agents, particularly
      considering the new findings concerning the mediators of inflammation, such as
      prostaglandins and nitric oxide. In fact, the discovery of two isoforms of the
      enzyme cyclooxygenase, which catalyzes the conversion of arachidonic acid to
      prostaglandins, has opened new interesting perspectives in the treatment of
      inflammatory diseases. As cyclooxygenase, also nitric oxide synthase, the enzyme
      which converts L-arginine to nitric oxide, exists in two isoforms. It appears
      that the constitutive isoforms of both enzymes (cyclooxygenase-1 and constitutive
      nitric oxide synthase) have a regulatory-physiological role, whereas the
      inducible isoforms (cyclooxygenase-2 and inducible nitric oxide synthase) are
      involved in inflammation. A number of medicinal plants have been screened for
      their ability to inhibit cyclooxygenase-2 and/or inducible nitric oxide synthase
      activity and/or expression.

PMID- 10930714
TI  - Phytotherapy and quality of herbal medicines.
AB  - The extensive use of plants as medicines has pointed out that herbal medicines
      are not as safe as frequently claimed. Therefore, it can be harmful to take
      herbal medicines without being aware of their potential adverse effects. A
      comprehensive surveillance system for monitoring the adverse effects of herbal
      medicines is now essential. Also knowledge of the correlation existing between
      the marker compounds and other ingredients that occur in plants is a necessary
      requirement for ensuring the efficacy and quality of the herbal medicines.

PMID- 10930715
TI  - Evaluation and use of plant biodiversity for food and pharmaceuticals.
AB  - Many epidemiological studies have shown the importance of fruit and vegetables in
      the human diet so as to prevent the onset of cardiovascular disease and several
      forms of cancer. The use for food and pharmaceuticals of two of the most widely
      grown and genetically well-known species in the world, the tomato and the potato,
      is reviewed. Tomatoes are important sources of vitamin C, potassium, folic acid
      and carotenoids such as lycopene and beta-carotene. It has been demonstrated that
      lycopene has anti-oxidant properties and interferes with the growth of cancerous
      cells. At the Department of Agronomy and Plant Genetics in Portici, interesting
      results have been obtained with the constitution of stable tomato hybrids having
      a high content of lycopene and vitamin C. Many of the parental lines used in
      constituting the hybrids come from interspecific crosses. Potato is also very
      important in the human diet for its content of high quality proteins, mineral
      salts and vitamins and it has many medicinal properties. The use of diploid wild
      species to transfer traits such as high content of vitamin C, mineral salts and
      high quality proteins into the cultivated potato through ploidy manipulation is
      discussed.

PMID- 10930716
TI  - Obesity and medicinal plants.
AB  - The effects of some medicinal plants (i.e. Fucus vesiculosus, Citrus aurantium)
      that are claimed to be useful in the treatment of obesity are reviewed.

PMID- 10930717
TI  - The role of ethnobotanics in scientific research. State of ethnobotanical
      knowledge in Sicily.
AB  - This contribution deals with the traditional use of plants of the Sicilian flora.
      Special attention is given to the species used in popular medicine. Moreover, the
      importance of ethnobotanics in scientific research and its role in toxicology are
      shown.

PMID- 10930718
TI  - An ethnopharmacological study on common privet (Ligustrum vulgare) and phillyrea
      (Phillyrea latifolia).
AB  - Ligustrum vulgare and Phillyrea latifolia leaves were well known in the
      Mediterranean historical medicine for their oropharyngeal anti-inflammatory
      effects. At the present time a popular phytotheraputical use of these species
      remains only in a few isolated southern European areas. Phytochemical and
      phytopharmacological studies of the methanolic extractives of their leaves were
      carried out. Flavonoidic fractions as well as different isolates, apigenin and
      luteolin derivatives showed significant in vitro complement inhibiting effects on
      the classical pathway of the complement system. A possible phytoceutical
      utilisation of the aerial parts of these species could represent (especially
      regarding the genus Phillyrea) an interesting perspective for many semi-arid
      Mediterranean regions.

PMID- 10930719
TI  - Ethnopharmacobotany in Tuscany: plants used as antihypertensives.
AB  - Among the more than 400 plants used in popular medicine in Tuscany, over 30 are
      used in the therapy of hypertension. For some of them their use is already known
      while for others there is no documentation. In this work we present the first
      results obtained from research carried out on antihypertensive plants belonging
      to Gentianaceae and in particular Gentiana kokiana.

PMID- 10930720
TI  - Immunopharmacological properties of flavonoids.
AB  - The flavonoids are a heterogeneous group of ubiquitous plant polyphenols that
      abound in the human diet and are endowed with several biological activities,
      including immunomodulating and antioxidant activities. The bioactivity of
      flavonoids is tightly correlated with their chemical structure and action
      mechanisms, mostly inhibitory, on enzymatic systems involved in cellular
      activation. The aim of this study was to evaluate the effects of acetonic
      extracts from Lunularia cruciata gametophytes and Feijoa sellowiana fruits on
      human phagocyte functions. A purified native flavonoid, a catechin, and two of
      its derivatives were also tested. The extract, and its flavonoid activity, was
      evaluated by analyzing luminol-dependent chemiluminescence emitted by human
      circulating phagocytes, at rest or activated by phorbol miristate acetate (PMA).
      The results demonstrate that both the raw extracts and flavonoids significantly
      inhibit CL emission by leukocytes, especially when these cells are activated by
      PMA. The antioxidant activity of flavonoids can be increased by changing the
      chemical structure of the native molecule.

PMID- 10930721
TI  - Antibacterial and allelopathic activity of extract from Castanea sativa leaves.
AB  - Following the extraction of Castanea sativa with an aqueous solution of sulfuric
      acid (pH 3.0), the ethyl acetate soluble fraction was tested for its
      antibacterial and allelopathic activity. The extract was shown to have pronounced
      antibacterial effects against seven of the eight strains of Gram-positive and
      Gram-negative bacteria used (MIC in the range of 64-256 microg/ml and MBC in the
      range of 256-512 microg/ml). The active fraction was analyzed by TLC and HPLC
      showing the presence of rutin, hesperidin, quercetin, apigenin, morin, naringin,
      galangin and kaempferol. Standards of the identified flavonoids were tested
      against the same bacterial strains. The highest activity was shown by quercetin,
      rutin and apigenin. The allelopathic effect was tested against Raphanus sativus
      seed germination. The extract, quercetin, rutin and apigenin caused a decrease in
      the percentage of seed germination and root and epicotyl growth.

PMID- 10930722
TI  - Behavioral characterisation of the flavonoids apigenin and chrysin.
AB  - The behavioral effects of acute administration of two flavonoids, apigenin and
      chrysin, contained in Matricaria chamomilla and in Passiflora incarnata,
      respectively, were studied in rats. The data demonstrate that in our experimental
      conditions, the two flavonoids were equally able to reduce locomotor activity
      when injected in rats at a minimal effective dose of 25 mg/kg. However, while
      chrysin exhibited a clear anxiolytic effect when injected at the dose of 1 mg/kg,
      apigenin failed to exert this activity. The sedative effect of these flavonoids
      cannot be ascribed to an interaction with GABA-benzodiazepine receptors, since it
      was not counteracted by the benzodiazepine antagonist Flumazenil. To the
      contrary, the anxiolytic effect of chrysin, which was blocked by the injection of
      Flumazenil, could be linked to an activation of the GABA(A) receptor unit.

PMID- 10930723
TI  - Pro-cognitive activity induced in the rat by low doses of R-(+)-hyoscyamine.
AB  - In the passive-avoidance test R-(+)-hyoscyamine (10-100 microg kg(-1) i.p.)
      prevented amnesia induced by antimuscarinic treatment with AF-64A and benzhexol.
      The antiamnesic effect of R-(+)-hyoscyamine was comparable to that exerted by the
      cholinesterase inhibitor physostigmine (0.2 mg kg(-1) i.p) and the M(1) selective
      agonist AF-102B (10 mg kg(-1) i.p.). In the social learning test, R-(+)
      hyoscyamine (10-100 microg kg(-1) i.p.) in adults rats, reduced the duration of
      active exploration of the familiar partner in the second session of the test
      similar to the nootropic drug piracetam (30 mg kg(-1) i.p.). These results
      demonstrated the ability of R-(+)-hyoscyamine to modulate memory functions and
      suggest that R-(+)-hyoscyamine could be useful in the treatment of cognitive
      deficits.

PMID- 10930724
TI  - Preventive effect of eugenol on PAF and ethanol-induced gastric mucosal damage.
AB  - This study examines the anti-ulcerogenic activity of eugenol, a natural compound
      obtained from many natural sources. Gastric ulcers, induced by administration of
      two ulcerogenic agents, i.e. platelet activating factor (PAF) and ethanol, were
      dose-dependently and significantly reduced by eugenol (10-100 mg/kg, p.o.) pre
      treatment. Eugenol was able to reduce not only the number of ulcers but also the
      gravity of lesions.

PMID- 10930725
TI  - Antimicrobial activity of crude extracts and pure compounds of Hypericum
      hircinum.
AB  - The antimicrobial activity of the n-hexane (H) and chloroform (C) extracts, the
      methanol extract (M) and its ethyl acetate (E) and n-butanol (B) fractions, and
      six isolated constituents of the aerial parts of Hypericum hircinum was
      investigated using an agar diffusion method. The maximum activity was exhibited
      by the methanolic extract against Staphylococcus aureus, while all pure
      constituents showed no antimicrobial activity against the tested microorganisms.

PMID- 10930726
TI  - Genes controlling circadian rhythm are widely distributed in cyanobacteria.
AB  - The kaiABC gene cluster is important for maintaining circadian rhythms in the
      cyanobacterium Synechococcus PCC 7942. An extensive PCR-based survey of
      phylogenetically diverse cyanobacteria was conducted using degenerate primers
      designed to identify the presence of the kaiC gene. Hybridization and sequence
      analyses showed that the observed amplification products had a high degree of
      similarity to kaiC. Forty cyanobacterial strains possessed kaiC related
      sequences, suggesting that a clock system is universal among cyanobacteria.

PMID- 10930727
TI  - Pseudomonas aeruginosa B-band lipopolysaccharide genes wbpA and wbpI and their
      Escherichia coli homologues wecC and wecB are not functionally interchangeable.
AB  - The O antigen unit of Pseudomonas aeruginosa serotype O5 is a complex
      trisaccharide containing 2-acetamido-3-acetiminido-2, 3-dideoxy-beta-D-mannuronic
      acid, 2-acetimido-3-acetimido-2, 3-dideoxy-beta-D-mannuronic acid, and 2
      acetimido-2, 6-deoxy-beta-D-galactosamine. Specific knockout mutations in the
      putative UDP-D-N-acetylglucosamine (UDP-D-GlcNAc) epimerase gene, wbpI, or the
      putative UDP-D-N-acetylmannosamine dehydrogenase gene, wbpA, resulted in strains
      that no longer produced B-band lipopolysaccharide, confirming the essential roles
      of these genes in B-band O antigen synthesis. Despite approximately 50%
      similarity of wbpI and wbpA to the Escherichia coli genes wecB (rffE) and wecC
      (rffD) involved in enterobacterial common antigen synthesis, cross
      complementation experiments were not successful. These results imply that the P.
      aeruginosa UDP-D-GlcNAc precursor may be di-N-acetylated prior to further
      modification, preventing the E. coli enzymes from recognizing it as a substrate.

PMID- 10930728
TI  - Isolation and characterization of acid- and Al-tolerant microorganisms.
AB  - Acid- and aluminum (Al)-tolerant microorganisms were isolated from tea fields,
      from which six strains were selected and identified as Cryptococcus humicola,
      Rhodotorula glutinis, Aspergillus flavus Link, Penicillium sp., Penicillium
      janthinellum Biourge and Trichoderma asperellum. They were tolerant to Al up to
      100-200 mM and could grow at low pH, 2.5-2.2. In a glucose medium (pH 3.5) the pH
      of the spent medium decreased to below 3.0. The toxic inorganic monomeric Al in
      the spent medium decreased with three strains (A. flavus F-6b, Penicillium sp. F
      8b and P. janthinellum F-13), but the total Al remained constant for all strains.
      In a soil extract medium (pH 3.5), the pH of the spent medium of all strains
      increased to around 6.0-7. 2 and total Al in the spent medium was removed by
      precipitation due to pH increase. Thus, different tolerance mechanisms were
      suggested in glucose and soil extract media.

PMID- 10930729
TI  - The modification of the membrane of Oceanomonas baumannii when subjected to both
      osmotic and organic solvent stress.
AB  - Oceanomonas baumanniioff a novel halotolerant bacterium which was isolated from
      the estuary of the river Wear (Sunderland, UK). When grown in tryptone soya broth
      it can tolerate high levels of phenol, which is not utilised as a carbon source
      in this medium. However, the level of tolerance was reduced from 35 mM to 3 mM
      phenol as salinity increased from 1% to 12% NaCl (w/v). Increasing salinity up to
      12% NaCl also decreased the growth rate 8-fold and caused modifications to the
      cytoplasmic membrane particularly anionic phosphatidylglycerol levels, which
      doubled at the expense of zwitterionic phosphatidylethanolamine. In addition,
      changes in the phospholipid fatty acid composition were noted, cis-vaccenic acid
      decreased significantly at higher salinities. Intracellular solute levels also
      increased with increasing salinity and there was an accumulation of the
      compatible solutes ectoine, glycine betaine and glutamate. The addition of phenol
      to osmotically compromised cultures led to a further modification of the
      cytoplasmic membrane phospholipid composition, in particular, that the decrease
      in zwitterionic phosphatidylethanolamine and the increase of anionic phospholipid
      species was much less pronounced. A further decrease in unsaturation,
      particularly in the proportion of cis-vaccenic acid, and the mean chain length of
      the fatty acids suggested that this response was important in maintaining
      membrane integrity in the presence of phenol.

PMID- 10930730
TI  - Immuno-crossreactivity and toxicity assessment of conjugation products of the
      cyanobacterial toxin, microcystin-LR.
AB  - Immunoassays are increasingly used to investigate the production, properties and
      fates of the cyanobacterial hepatotoxic microcystins in vitro and in vivo.
      Responses of an ELISA immunoassay to microcystins have been determined using the
      authentic toxin antigen, microcystin-LR, and conjugation products between the
      toxin and glutathione, cysteine-glycine and cysteine. The antibodies against
      microcystin-LR crossreacted with the toxin conjugation products with similar
      affinities (96-112%) to that of microcystin-LR, when assayed at a concentration
      of 1 microg l(-1). Toxicity assessment of the conjugates, in comparison to
      microcystin-LR, indicated a reduction according to mouse bioassay. In vitro
      protein phosphatase inhibition assay indicated that the conjugates possessed
      approximately 3-9-fold lower toxicity than microcystin-LR.

PMID- 10930731
TI  - Cloning and sequencing of the triacylglycerol lipase gene of Aspergillus oryzae
      and its expression in Escherichia coli.
AB  - Aspergillus oryzae produces at least three extracellular lipolytic enzymes, L1,
      L2 and L3 (cutinase, mono- and diacylglycerol lipase, and triacylglycerol lipase,
      respectively). We cloned the triacylglycerol lipase gene (provisionally
      designated tglA) by screening a genomic library using a PCR product obtained with
      two degenerate oligonucleotide primers corresponding to amino acid sequences of
      L3 as probes. Nucleotide sequencing of the genomic DNA and cDNA revealed that the
      L3 gene (tglA) has an open reading frame comprising 954 nucleotides, which
      contains three introns of 47, 83 and 62 bp. The deduced amino acid sequence of
      the tglA gene corresponds to 254 amino acid residues including a signal sequence
      of 30 amino acids and, in spite of the difference in substrate specificity, it is
      homologous to those of cutinases from fungi. Three residues presumed to form the
      catalytic triad, Ser, Asp and His, are conserved. The cloned cDNA of the tglA
      gene was expressed in Escherichia coli, and enzyme assaying and zymography
      revealed that the cloned cDNA encodes a functional triacylglycerol lipase.

PMID- 10930732
TI  - Ribonuclease U2: cloning, production in Pichia pastoris and affinity
      chromatography purification of the active recombinant protein.
AB  - RNase U2 is an endoribonuclease secreted by the fungus Ustilago sphaerogena. Its
      genomic DNA (rnu2), containing an intron of 116 bp, has been isolated and cloned.
      The corresponding cDNA has also been synthesized. The recombinant RNase U2 was
      successfully produced in Pichia pastoris, fused to the yeast alkaline phosphatase
      signal peptide. The recombinant RNase U2, purified by affinity chromatography,
      contains three extra amino acids at its amino-terminal end and retains the
      enzymatic and spectroscopic properties of the natural fungal protein.

PMID- 10930733
TI  - An oxidation domain in the BlmIII non-ribosomal peptide synthetase probably
      catalyzing thiazole formation in the biosynthesis of the anti-tumor drug
      bleomycin in Streptomyces verticillus ATCC15003.
AB  - We have previously proposed that the BlmIV and BlmIII non-ribosomal peptide
      synthetases are involved in the formation of the bithiazole moiety of the anti
      tumor drug bleomycin in Streptomyces verticillus ATCC15003. We report here the
      identification and characterization of an oxidation domain in BlmIII. The
      oxidation domain shows local homology to a family of oxidoreductases and is
      present in all thiazole-forming non-ribosomal peptide synthetase modules known to
      date. Both the blmIII-Ox domain and blmIII gene were expressed in Escherichia
      coli, and the resulting BlmIII-Ox and BlmIII proteins were purified to
      homogeneity. The oxidation domain contains one molar equivalent of non-covalently
      bound FMN as a prosthetic group. These results provide experimental evidence for
      an oxidation domain within non-ribosomal peptide synthetases, suggesting that
      BlmIII-Ox probably catalyzes the thiazoline to thiazole oxidation in bleomycin
      biosynthesis.

PMID- 10930734
TI  - The L-asparagine operon of Rhizobium etli contains a gene encoding an atypical
      asparaginase.
AB  - The L-asparagine operon of Rhizobium etli was cloned and sequenced. Sequence
      analysis showed four adjacent open reading frames which were designated as ansR,
      ansP, ansA and ansB. The ansR and ansP genes encoded proteins similar to a
      transcriptional repressor and an L-asparagine permease, respectively. By Tn5
      mutagenesis and complementation analysis we identified the ansA product as a
      thermolabile asparaginase, and the ansB product as an aspartase. An asparagine
      inducible transcript covering ansP, ansA and ansB was detected by reverse
      transcription (RT)-PCR, indicating that these genes are organized in an operon.
      Introduction of the R. etli ans operon into Sinorhizobium meliloti induced growth
      with asparagine as the sole carbon and nitrogen source, suggesting that the ans
      operon plays the same physiological role in both bacteria. The product of the R.
      etli ansA gene showed no sequence similarity with previously reported microbial
      asparaginases, this protein seems to be an atypical asparaginase which evolved
      apart from bacterial and yeast asparaginases.

PMID- 10930735
TI  - Purification and characterization of histamine dehydrogenase from Nocardioides
      simplex IFO 12069.
AB  - Histamine dehydrogenase from Nocardioides simplex IFO 12069 was purified to
      homogeneity. The enzyme had a molecular mass of 170 kDa and was suggested to be a
      dimer of subunits that had a molecular mass of 84 kDa. The enzyme showed highest
      activity toward histamine and produced ammonia in its oxidative deamination to
      imidazole acetaldehyde. The K(m) and V(max) values for histamine were 0.075 mM
      and 4.76 micromol min(-1) mg(-1), respectively. The enzyme was sensitive to the
      carbonyl reagent iproniazid and a structurally similar compound, tryptophan. The
      enzyme showed absorption maxima at 442 and 280 nm. Reduction with histamine under
      anaerobic conditions resulted in a different absorption maximum at 360 nm instead
      of 442 nm. The enzyme was most active at pH 8.5 in Tris-HCl buffer and most
      stable at pH 7.0 in potassium phosphate buffer. The E(1%) value of the enzyme was
      8.6 at 280 nm.

PMID- 10930736
TI  - The identification and characterisation of an unusual genotype of Cryptosporidium
      from human faeces as Cryptosporidium meleagridis.
AB  - An unusual genotype of Cryptosporidium was identified in the faeces of six human
      patients by PCR/RFLP analysis of the Cryptosporidium oocyst wall protein (COWP)
      gene. Conventional microscopy showed oocysts indistinguishable in size from those
      of Cryptosporidium parvum, which reacted with two different commercially
      available anti-oocyst monoclonal antibodies. The isolates were further
      characterised by PCR/RFLP analysis of the thrombospondin-related adhesive protein
      of Cryptosporidium-1 (TRAP-C1) genes as well as by DNA sequencing of the COWP and
      the TRAP-C1 gene fragments and of two regions of the 18S rRNA gene. Sequence
      analysis of the COWP, TRAP-C1, and 18S rRNA gene fragments confirmed that this
      genotype is genetically distinct from C. parvum. 18S rRNA gene sequences were
      found to be identical to those published for Cryptosporidium meleagridis.

PMID- 10930737
TI  - Pyridoxal kinase knockout of Dictyostelium complemented by the human homologue.
AB  - The gene (pykA) encoding pyridoxal kinase which converts pyridoxal (vitamin B(6))
      to pyridoxal phosphate was isolated from Dictyostelium discoideum using
      insertional mutagenesis. Cells of a pykA gene knockout grew poorly in axenic
      medium with low yield but growth was restored by the addition of pyridoxal
      phosphate. Sequencing indicated a gene, with one intron, encoding a predicted
      protein of 301 amino acids that was 42% identical in amino acid sequence to human
      pyridoxal kinase. After expression of the wild-type gene in Escherichia coli, the
      purified PykA protein product was shown to have pyridoxal kinase enzymatic
      activity with a K(m) of 8.7 microM for pyridoxal. Transformation of the
      Dictyostelium knockout mutant with the human pyridoxal kinase gene gave almost
      the same level of complementation as that seen using transformation with the wild
      type Dictyostelium gene. Phylogenetic analysis indicated that the Dictyostelium
      amino acid sequence was closer to human pyridoxal kinase than to pyridoxal
      kinases of lower eukaryotes.

PMID- 10930738
TI  - Two-step procedure for purification and separation of the essential penicillin
      binding proteins PBP 1A and 1Bs of Escherichia coli.
AB  - The penicillin-binding proteins PBP 1A and 1Bs are the essential murein
      polymerases of Escherichia coli. Purification of these membrane-bound
      bifunctional transglycosylase-transpeptidases was a major obstacle in studying
      the details of both enzymatic reactions. Here we describe a simple, highly
      specific affinity chromatography method that takes advantage of the availability
      of the specific inhibitor of the transglycosylase site moenomycin A in order to
      enrich PBP 1A and 1Bs in one step from crude membrane preparations. Separation of
      PBP 1A from PBP 1Bs is achieved in a second step employing cation exchange
      chromatography yielding enzymatically active native murein polymerases.

PMID- 10930740
TI  - Purification and characterization of a membrane-associated ATPase from
      Natronococcus occultus, a haloalkaliphilic archaeon.
AB  - Isolated membranes of the extreme haloalkaliphilic archaeon Natronococcus
      occultus were able to hydrolyze ATP via an ATPase, which required the presence of
      Mg(2+), high concentrations of NaCl, and a pH value of 9. The native molecular
      mass of the purified ATPase was 130 kDa and was composed of 74- and 61-kDa
      subunits. Enzyme activity was specific for the hydrolysis of ATP with slight
      activity towards GTP, CTP, and ITP. The enzyme required NaCl for maximal activity
      but Na(2)SO(4) and (NH(4))(2)SO(4) could substitute. The enzyme showed no
      activity if Na(2)SO(3) or sodium citrate was substituted for NaCl. The ATPase
      from N. occultus was inhibited by NBD-Cl, NaN(3), and ouabain, and was sensitive
      to nitrate, vanadate, DCCD, and bafilomycin A(1). It was not inhibited by NEM in
      contrast to other previously characterized halophile ATPases. The ATPase had a
      K(M) of 0.5 mM and appeared to be non-competitively inhibited by NaN(3) with a
      K(I) of 3.1 mM.

PMID- 10930739
TI  - Cysteine biosynthesis in the Archaea: Methanosarcina thermophila utilizes O
      acetylserine sulfhydrylase.
AB  - Two pathways for cysteine biosynthesis are known in nature; however, it is not
      known which, if either, the Archaea utilize. Enzyme activities in extracts of
      Methanosarcina thermophila grown with combinations of cysteine and sulfide as
      sulfur sources indicated that this archaeon utilizes the pathway found in the
      Bacteria domain. The genes encoding serine transacetylase and O-acetylserine
      sulfhydrylase (cysE and cysK) are adjacent on the chromosome of M. thermophila
      and possibly form an operon. When M. thermophila is grown with cysteine as the
      sole sulfur source, O-acetylserine sulfhydrylase activity is maximally expressed
      suggesting alternative roles for this enzyme apart from cysteine biosynthesis.

PMID- 10930741
TI  - Structural studies of microcosm dental plaques grown under different nutritional
      conditions.
AB  - The aim of this study was to investigate the structure of intact oral biofilms
      using confocal laser scanning microscopy (CLSM). Mixed-species biofilms were
      grown on enamel discs in a constant depth film fermentor. The biofilms were fed
      with a mucin-containing artificial saliva with or without sucrose
      supplementation. Biofilms were examined using a Wild-Leitz CLSM, operating in
      reflected light mode. The microstructure of non-supplemented biofilms was
      revealed to be complex, with stacks of bacteria developing over time, separated
      by clear channels. Sucrose-supplemented biofilms appeared to colonise the
      substratum more rapidly. The results of this study have shown that using CLSM it
      is possible to examine the structure of oral biofilms grown under conditions
      similar to those which would exist in vivo.

PMID- 10930742
TI  - Antibiotic production in relation to bacterial growth and nematode development in
      Photorhabdus--Heterorhabditis infected Galleria mellonella larvae.
AB  - The population of Photorhabdus luminescens C9, bacterial symbiont of the
      entomopathogenic nematode, Heterorhabditis megidis 90, increased rapidly to 1.2
      2.6x10(9) cells g(-1) wet Galleria mellonella larvae within 24 h of nematode
      infection of the larvae, and maintained a relatively constant level (1.2
      2.0x10(10) cells g(-1)) through the entire 14-day period of nematode development.
      The antibiotic, 3, 5-dihydroxy-4-isopropylstilbene, was produced by P.
      luminescens C9 after 24 h of nematode infection, increased rapidly at 2-5 days
      postinfection and remained at a level of 3000-3600 microg g(-1) wet larvae until
      about 21 days, decreasing gradually thereafter. The early production and
      continued presence of a relatively large amount of 3,5-dihydroxy-4
      isopropylstilbene in the infected insect supports the hypothesis that the
      antibiotics produced by the bacterial symbiont help minimize competition from
      other microorganisms and prevents the putrefaction of the nematode-infected
      insect cadaver.

PMID- 10930743
TI  - Cellular actin is affected by interaction with Candida albicans.
AB  - Attachment of Candida albicans, an important opportunistic pathogen, to host
      tissues is an initial step in the development of the infection. The events
      occurring in the fungal and in the host cells after interaction are poorly
      understood. In this study we concentrated on the events occurring in the
      mammalian cells after the interaction with Candida, with emphasis on the
      cytoskeleton actin. Human cell line cells (HEp2) were exposed to C. albicans or
      C. albicans-secreted material (culture filtrate) (actin-rearranging Candida
      secreted factor, arcsf). The HEp2 cells were examined for cellular changes using
      confocal laser microscopy (CLSM), transmission and scanning electron microscopy
      (TEM and SEM). The CLSM studies, using fluorescein isothiocyanate-labeled C.
      albicans and rhodamine phalloidin actin staining, revealed yeasts adhering to the
      HEp2 cells or internalized into the cells, with actin surrounding the fungi.
      Furthermore, actin rearrangement from filamentous network to actin aggregates was
      noticed. Interaction between the HEp2 cells and C. albicans could be demonstrated
      also by SEM and TEM after a 2-4-h exposure of the cells to the fungus. Yeasts and
      hyphae were found attaching to the surface and within the cells. CLSM studies
      revealed that exposure of HEp2 cells to arcsf was also followed by cellular actin
      rearrangement, reduced membrane ruffling and decreased cellular motility. The
      effect was dose- and time-dependent. All these data indicate that the interaction
      of Candida with HEp2 cells involves signaling events and affects the cellular
      actin.

PMID- 10930744
TI  - Can the grey mould disease of the grape-vine be controlled by yeast?
AB  - Botrytis cinerea has been found to be highly pathogenic to 'Chardonnay' and
      'Pinot noir' cultivars of the grape-vine producing the characteristic grey mould
      symptoms within 7 days of inoculation to the vitro-plants. The yeast Pichia
      anomala (strain FY-102), isolated from apple skin, was found to be antagonistic
      to B. cinerea as it completely inhibited the appearance of the grey mould
      symptoms when grown together. The yeast was responsible for morphological changes
      such as coagulation and leakage of the cytoplasm of B. cinerea. The pathogen,
      when applied together with P. anomala, failed to bring about the grey mould
      symptoms on the grape-vine, suggesting that the yeast could control the
      expression of this disease. An account of the interaction between B. cinerea and
      P. anomala, as well as the sequences of the complete ITS region of the ribosomal
      DNA of the yeast are described here.

PMID- 10930745
TI  - Characterisation of a Rrhodobacter sphaeroides gene that encodes a product
      resembling Eescherichia coli cytochrome b(561) and R. sphaeroides cytochrome
      b(562).
AB  - Analysis of the photoactive yellow protein (pyp) gene region of Rhodobacter
      sphaeroides has revealed the presence of an additional open reading frame, orfD,
      that had not previously been identified. Here we report the location of this new
      gene and the predicted amino acid sequence of the encoded protein. The
      translation product resembles a group of small cytochrome b-like proteins,
      including Escherichia coli cytochrome b(561), R. sphaeroides cytochrome b(562),
      and two new cytochrome b(561)-like proteins identified using the E. coli genome
      sequence, for which functions have not yet been established. To determine OrfD
      function in R. sphaeroides, an orfD mutant was constructed. The OrfD mutant
      exhibited growth rates and yields very similar to those of the wild-type strain
      when grown under a variety of growth conditions. Respiration rates, reduced-minus
      oxidised spectra and levels of photosynthetic complexes were also very similar in
      the two strains. Although the role of OrfD was therefore not determined here, we
      demonstrate that the orfD gene is expressed in R. sphaeroides under aerobic, semi
      aerobic and photosynthetic growth conditions.

PMID- 10930746
TI  - Identification of Yersinia pestis as the causative organism of plague in India as
      determined by 16S rDNA sequencing and RAPD-based genomic fingerprinting.
AB  - Eighteen isolates of bacteria obtained from the sputum of pneumonic plague
      patients and from the liver and spleen of rodents from the plague-affected areas
      of India during 1994-1995 when analyzed by 16S rDNA analysis clearly demonstrated
      that all 18 isolates exhibit an average similarity of 98.5% with the genus
      Yersinia and 99.1% with Yersinia pestis, thus identifying the isolates as Y.
      pestis. The isolates from the human plague patients were found to be genetically
      more homogeneous compared to the isolates from the rodents which were more
      heterogeneous. An epidemiological linkage among the rodents and human patients is
      also indicated by 16S rDNA analysis, which suggests that only a sub-population of
      the rodents was probably the source of the infectious pathogen to the humans
      initiating the outbreak of the epidemic. The results of the randomly amplified
      DNA polymorphisms (RAPD)-based DNA fingerprinting are in agreement with the above
      conclusions.

PMID- 10930747
TI  - The tyrosine aminotransferase from Trypanosoma rangeli: sequence and genomic
      characterization.
AB  - The complete sequence and genomic characterization of the tyrosine
      aminotransferase (TAT) gene from Trypanosoma rangeli is reported. The gene was
      found to be organized in a tandem multicopy gene array. A homologous mRNA species
      (2.5 kb) was identified in the epimastigote form of the parasite. From the
      deduced amino acid sequence, the gene encodes a protein of 420 amino acids with a
      predicted molecular mass of 46.4 kDa and a theoretical pI of 6.23. A high
      sequence identity was found with the Trypanosoma cruzi, human and rat enzymes.
      All the essential residues for TAT enzymatic activity are conserved, as well as a
      pyridoxal-phosphate attachment site typical of class-I aminotransferases. The
      recombinant enzyme was recognized by a monoclonal antibody against the T. cruzi
      enzyme. Additionally, the recombinant protein showed enzymatic activity when
      incubated with L-tyrosine and 2-oxoglutaric acid as substrates.

PMID- 10930748
TI  - Extracellular polysaccharide composition of Azospirillum brasilense and its
      relation with cell aggregation.
AB  - The exopolysaccharide (EPS) and capsular polysaccharide (CPS) composition of four
      Azospirillum brasilense strains differing in their aggregation capacity was
      analyzed by high performance anion exchange chromatography. When growing the
      different strains in an aggregation inducing medium containing a high
      carbon:nitrogen (C:N) ratio, both EPS and CPS showed a positive correlation
      between aggregation and the relative amount of arabinose. Arabinose was not
      detected in polysaccharides from Sp72002, a pleiotrophic Tn5 mutant strain
      impaired in aggregation. Arabinose was also not detected in extracellular
      polysaccharides of bacteria grown in a low C:N ratio, non-inducing aggregation
      medium, with exception for a relatively small amount found in the CPS of FAJ0204,
      a super-aggregating mutant strain. The only monosaccharides able to significantly
      inhibit aggregation at low sugar concentration when tested in a bioassay were
      arabinose (at a higher extent) and galactose. The possibility that residues of
      arabinose present in the extracellular polysaccharides are involved in the
      aggregation of A. brasilense is discussed.

PMID- 10930749
TI  - Multiplex PCR for the identification of white Tuber species.
AB  - Species-specific primers selected from the internal transcribed spacer region
      sequence were used to set up a multiplex polymerase chain reaction (PCR) able to
      simultaneously identify the white truffle species Tuber magnatum, Tuber borchii,
      Tuber maculatum and Tuber puberulum. Furthermore, a primer specific for the
      competitive fungus Sphaerosporella brunnea was designed and added to the
      multiplex PCR set, allowing the detection of the Tuber species and the
      contaminant fungus in a one-step reaction.

PMID- 10930750
TI  - The Giardia genome project database.
AB  - The Giardia genome project database provides an online resource for Giardia
      lamblia (WB strain, clone C6) genome sequence information. The database includes
      edited single-pass reads, the results of BLASTX searches, and details of progress
      towards sequencing the entire 12 million-bp Giardia genome. Pre-sorted BLASTX
      results can be retrieved based on keyword searches and BLAST searches of the high
      throughput Giardia data can be initiated from the web site or through NCBI.
      Descriptions of the genomic DNA libraries, project protocols and summary
      statistics are also available. Although the Giardia genome project is ongoing,
      new sequences are made available on a bi-monthly basis to ensure that researchers
      have access to information that may assist them in the search for genes and their
      biological function. The current URL of the Giardia genome project database is
      www.mbl.edu/Giardia.

PMID- 10930751
TI  - S-layer gene as a molecular marker for identification of Lactobacillus
      helveticus.
AB  - The paper describes two methods that allow rapid and accurate identification of
      Lactobacillus helveticus strains based on the nucleotide sequence of the gene
      coding for the surface layer (S-layer) protein. The first method is based on a
      polymerase chain reaction amplification using primers targeting a specific
      fragment of the S-layer gene. The second method involved a portion of the S-layer
      gene of L. helveticus as a probe in a hybridisation test. The specificity of
      these protocols was checked for DNA samples isolated from various Lactobacillus
      strains.

PMID- 10930752
TI  - NeuD plays a role in the synthesis of sialic acid in Escherichia coli K1.
AB  - The polysialic acid capsule of Escherichia coli K1 is an essential virulence
      determinant. The kps gene cluster, which encodes the proteins necessary for
      polymer synthesis and transport, is divided into three functional regions. In
      this report, we present evidence that the neuD gene from region 2 is involved in
      sialic acid synthesis. A non-polar chromosomal deletion in neuD was constructed.
      The defect was complemented by neuD in trans or by the addition of exogenous
      sialic acid. A NeuD homologue, Neu(III)D, from serotype III Streptococcus
      agalactiae (GBS) also restored capsule expression to the neuD deletion strain.
      These data confirm the role of neuD in E. coli sialic acid capsule synthesis and
      demonstrate that the neu(III)D homologue from GBS shares a similar enzymatic
      function.

PMID- 10930753
TI  - Partial characterization of a genomic island associated with the multidrug
      resistance region of Salmonella enterica Typhymurium DT104.
AB  - This study describes the identification of the insertion site and partial
      characterization of a 43-kb region harboring the genes associated with the penta
      resistant phenotype of a Canadian isolate of Salmonella enterica Typhymurium
      DT104 labelled 96-5227. The 43-kb fragment, here referred to as Salmonella
      genomic island I (SgiI), was found in the genome of S. enterica Typhymurium
      between the thdf and a prophage CP-4-like integrase (int2) gene and is flanked by
      an imperfect 18-bp direct repeat. A region downstream of sulI in the right end of
      SgiI contained four open reading frames which includes an IS6100 element, and a 2
      kb region from the left end contained two open reading frames which showed
      homology to an integrase and an excisionase. Furthermore, a 1.9-kb retron
      sequence located between int2 and yidY was identified which may be unique to the
      S. enterica Typhymurium genome. The int-retron sequence is flanked by a 27-bp
      imperfect direct repeat.

PMID- 10930754
TI  - Replication origin of Streptococcus pyogenes, organization and cloning in
      heterologous systems.
AB  - The origin of DNA replication (oriC) of Streptococcus pyogenes, group A
      streptococci (GAS), has been cloned in Escherichia coli and reintroduced by
      transformation into other GAS strains. Transformation frequencies into GAS
      strains with oriC-carrying plasmids occurred with unusually high frequencies.
      However, the oriC-containing plasmids in the new recipients were found to be
      unstable and had a tendency to integrate into the chromosome, even when a recA
      GAS strain was used as a recipient. The GAS oriC was able to direct the
      replication of autonomous plasmids in group B streptococcal recipients. The
      chromosomal organization of the oriC region of GAS relative to other bacterial
      species appears to be similar to oriC of Bacillus subtilis and other Gram
      positive microorganisms.

PMID- 10930755
TI  - Inverted behavioural responses in wild-type Rhodobacter sphaeroides to temporal
      stimuli.
AB  - Both aerobically and photosynthetically grown wild-type Rhodobacter sphaeroides
      swarmed through soft nutrient agar. However, individual aerobically and
      photosynthetically grown tethered cells showed different responses to steps in
      concentrations of some attractants. Photosynthetically grown cells showed little
      response to a step-up in attractant, but large response to a step-down.
      Aerobically grown cells showed a large but opposite response to a step-up of
      chemoeffectors such as succinate and aspartate. The responses in che operon
      deletion mutants were also investigated and indicated that the aerobic response
      may depend on the protein products of che operon 1.

PMID- 10930756
TI  - Urease of Corynebacterium glutamicum: organization of corresponding genes and
      investigation of activity.
AB  - The Corynebacterium glutamicum genes encoding urease were isolated and sequenced.
      While ureA, ureB and ureC are encoding structural subunits of urease, ureE, ureF,
      ureG and ureD are encoding accessory proteins. As deduced from DNA sequence
      analyses, the ure genes are transcriptionally coupled, this was proven by RT-PCR
      at least for ureABC. Gene disruption experiments revealed that both structural
      (UreC) and accessory proteins (UreD) are indispensable for urease activity and
      growth on urea. Urease activity was determined in different Corynebacterium
      species after growth in various media. While the regulation patterns observed
      revealed species-specific differences, in general urease activity is induced upon
      nitrogen starvation. As in mycobacteria, in corynebacteria urease activity was
      highest in a pathogenic species and might also play a role in host-pathogen
      interaction.

PMID- 10930757
TI  - Retention of bacteria on a substratum surface with micro-patterned
      hydrophobicity.
AB  - Bacteria adhere to almost any surface, despite continuing arguments about the
      importance of physico-chemical properties of substratum surfaces, such as
      hydrophobicity and charge in biofilm formation. Nevertheless, in vivo biofilm
      formation on teeth and also on voice prostheses in laryngectomized patients is
      less on hydrophobic than on hydrophilic surfaces. With the aid of micro-patterned
      surfaces consisting of 10-microm wide hydrophobic lines separated by 20-microm
      wide hydrophilic spacings, we demonstrate here, for the first time in one and the
      same experiment, that bacteria do not have a strong preference for adhesion to
      hydrophobic or hydrophilic surfaces. Upon challenging the adhering bacteria,
      after deposition in a parallel plate flow chamber, with a high detachment force,
      however, bacteria were easily wiped-off hydrophobic lines, most notably when
      these lines were oriented parallel to the direction of flow. Adhering bacteria
      detached slightly less from the hydrophilic spacings in between, but
      preferentially accumulated adhering on the hydrophilic regions close to the
      interface between the hydrophilic spacings and hydrophobic lines. It is concluded
      that substratum hydrophobicity is a major determinant of bacterial retention
      while it hardly influences bacterial adhesion.

PMID- 10930759
TI  - Renal medullary carcinoma: sonographic, computed tomography, magnetic resonance
      and angiographic findings.
AB  - Renal medullary carcinoma is a recently described, highly aggressive tumour,
      occurring predominantly in young patients of African descent with sickle cell
      trait (SCT). All have been metastatic at surgery. Surgery, radiotherapy and
      chemotherapy do not appear to alter the course of the disease. The survival time
      is very short. Presentation is usually with haematuria, abdominal pain and weight
      loss. Forty-nine patients have been reported from the USA, of these 47 were
      African/Americans. The reports have mostly appeared in pathology journals. On
      review of the imaging findings reported in the radiological journals, it becomes
      apparent that it is possible for a radiologist to suggest a specific diagnosis in
      the appropriate demographic and clinical setting. Here the first British patient
      of Afro-Caribbean decent in whom a pre-operative diagnosis was suggested on the
      imaging findings of a centrally located renal pelvic tumour, encasing the pelvis
      on a background of SCT in a 28-year-old is described. It is expected that a high
      index of suspicion in the appropriate clinical setting may lead to earlier
      diagnosis, treatment and survival of patients. The patient is alive and
      reasonably well 9 months after surgery. The full range of imaging findings in
      renal medullary carcinoma are described.

PMID- 10930760
TI  - MRI features of epidural extramedullary hematopoiesis.
AB  - A case of beta-thalassemia intermedia with spinal cord compression due to
      extramedullary hematopoiesis, which was successfully treated by blood
      transfusion, is presented. Emphasis was made on the MRI appearance of
      extramedullary hematopoiesis on different pulse sequences. The theories that
      aimed to explain the involvement of the epidural space by extramedullary
      hematopoiesis are discussed.

PMID- 10930761
TI  - CT presentation of Wegener's granulomatosis in a child: rapidly progressive
      changes of pulmonary nodules to cavities.
AB  - We present a child with Wegener's granulomatosis who showed lung lesions
      progressing from nodules to cavities within a 1-month period on CT.

PMID- 10930762
TI  - Bronchiolar disease: spectrum and radiological findings.
AB  - Two types of bronchiole, the terminal bronchiole and the respiratory bronchiole,
      have structural and functional differences. The former is characterized as a
      conducting airway and the latter is closely related to a gas-exchange function as
      it has numerous alveoli on the wall. Therefore, the diseases occurring at
      bronchiole demonstrate different pathological, radiological and clinical pictures
      depending on which bronchiole is mainly involved. The disease that mainly
      involves the conducting airway is appreciated as a small airway disease.
      Constrictive bronchiolitis is a well-recognized entity classified in this
      category. Whereas the disease mainly involves the respiratory bronchiole and
      distal alveolar space, it is recognized as an interstitial and parenchymal
      disease. BOOP or RB-ILD is classified in this category. These two types of
      bronchiolar diseases reveal the contrast clinical pictures, including incidence,
      causative disease, response to the treatment, prognosis, respiratory function
      test as well as the radiological findings. This pictorial essay will illustrate
      the radiological features of the varieties of bronchiolitis.

PMID- 10930763
TI  - Middle mediastinal lesions: imaging findings and pathologic correlation.
AB  - Lesions primarily involving the middle mediastinum are uncommon and include lymph
      node diseases, cystic lesions, neurogenic tumors, mesenchymal tumors, tumors of
      mediastinal organ, amd other benign processes. In this article, we illustrate
      imaging findings of a variety of middle mediastinal lesions with pathologic
      correlation.

PMID- 10930764
TI  - Mucinous (colloid) breast cancer: mammographic and US features with histologic
      correlation.
AB  - OBJECTIVE: Mucinous carcinoma of the breast presents with different survival
      rates in pure and mixed types. The purpose of this study was to correlate the
      mammographic and ultrasonographic findings of mucinous carcinoma with histologic
      features in different types and mucin rates. MATERIAL AND METHODS: Thirty-four
      patients (2.3%) had mucinous cancer after retrospective review of the 1439 breast
      cancers diagnosed between 1990 and 1996. Twenty-seven patients, 19 pure and eight
      mixed type of mucinous carcinomas of the breast, were included in this study to
      evaluate the imaging findings. In 22 of these, the microscopic slides were
      available and re-evaluated to estimate the volume of extracellular mucin. The
      volume of the extracellular mucin was classified histologically as: (+), less
      than 50% of mucin; (++), 50-80% of mucin; and ( ), more than 80% of mucin.
      Mammographic features with emphasis on margin characteristics and sonographic
      echo pattern of tumors were correlated with histologic findings. RESULTS: Ten
      cases (53%) of pure mucinous type carcinomas had a circumscribed mass lesion on
      the mammograms. The well-defined, lobulated margins of the masses were well
      correlated with pure histologic type (P<0.01; chi(2) analysis) Two-thirds of
      these tumors had high volume extracellular mucin. All mixed type mucinous
      carcinomas demonstrated poorly defined or spiculated margins with no relation to
      the mucin rates (P<0.01). The sonographic appearances of the tumors showed
      correlation with histologic types. Most of the pure type carcinomas (53%) were
      seen with isoechogenic echo texture relative to that of subcutaneous fat, while
      all of the mixed type carcinomas were hypoechogenic (P<0.01). CONCLUSION: The
      mammographic and sonographic features of mucinous breast carcinoma show
      differences in pure and mixed types of the tumor. The most common mammographic
      appearance of pure mucinous carcinomas with high percentages of mucin is a mass
      lesion having well-defined margins, which is isoechogenic relative to fat on the
      sonographic examination. Pure type of carcinomas with small percentages of mucin
      and mixed type carcinomas have more aggressive imaging characteristics.

PMID- 10930765
TI  - Can hysterosalpingocontrast-sonography replace hysterosalpingography in the
      assessment of tubal subfertility?
AB  - INTRODUCTION: Hysterosalpingo-contrastsonography (HyCoSy) is a new method for
      assessing tubal patency using transvaginal ultrasound. It is thought to have
      several advantages over conventional hysterosalpingography (HSG). We
      prospectively evaluated the performance of HyCoSy and HSG in the diagnosis of
      tubal pathology. METHODS AND PATIENTS: One-hundred consecutive subfertile women
      underwent both HyCoSy and HSG in randomised order. Results of both tests were
      related to findings at laparoscopy with dye, which was used as the reference
      test. Each woman was asked to score the pain exsperienced at both procedures on a
      visual analogue scale. RESULTS: When laparoscopy with dye was used as reference
      test, the likelihood ratios of HyCoSy were slightly inferior to those obtained
      for HSG. Since the performance of HyCoSy was dependent on experience, the results
      were recalculated omitting the 50 initial procedures from the analysis. In that
      calculation, results of HyCoSy and HSG were comparable. There were no differences
      in pain experienced during the procedure, as there appeared also to be no
      differences in patient preferences. CONCLUSION: There appear to be no strong
      arguments either to replace HSG by HyCoSy, or to reject the use of HyCoSy. Both
      procedures can be used in the evaluation of tubal pathology.

PMID- 10930766
TI  - Vesico-ureteral reflux: diagnosis and staging with voiding color Doppler US:
      preliminary experience.
AB  - INTRODUCTION: The aim of this study is to assess the accuracy of a new US
      examination: 'voiding color Doppler US ' in the early diagnosis and staging of
      vesico-ureteral reflux (VUR). The contrast agent US was SH U 508A (Levovist,
      Schering, Berlin), which produces a chromatic accentuation of the signals picked
      up by the color Doppler US. Eighteen patients (10 females, eight males) were
      recruited for the study. In two patients a second examination was performed for
      follow-up after a VUR conservative therapy. All patients were taken under
      examination for the evaluation of possible VUR. In all patients the voiding color
      Doppler US was followed by voiding cystourethrography (VCUG) and the data
      obtained were compared. MATERIALS AND METHODS: A total of 18 patients aged
      between 3 months and 10 years, were recruited for the study. The results of the
      examination were the following: urinary tract infections, follow-up of VUR after
      conservative or surgical therapy, miscellaneous indications. Voiding color
      Doppler US was performed, followed by a VCUG. The voiding color Doppler US
      consists in the trans-catheter introduction of a contrast agent SHU 508 A
      (Levovist, Schering, Ag. Berlin) into the bladder and a subsequent test with the
      color Doppler US to show or exclude the presence of reflux into the ureters
      and/or into the pyelo-caliceal cavity of the kidneys. After the introduction of
      the contrast agent US the ultrasound scanning of the bladder, the ureters and the
      pyelo-caliceal cavity was performed to examine the reflux degree. The
      ultrasonographic investigations were perfomed with AU 590 asyncronus US (Esaote
      Biomedica, Genova) with a 3.5 MHz convex probe. RESULTS: After the trans-catheter
      introduction of the contrast agent US, vesico-ureteral reflux occured in 13
      patients (77.2%). The reflux degree was also measured by means of ultrasound and
      was later confirmed by VCUG. The mean times of each examination were as follows:
      initial US, 10 min; catheterization, 8 min; voiding color Doppler US, 15 min;
      overall VCURG examination 10 min. The overall mean duration of the voiding color
      Doppler US examination was 33 min. The comparable mean time for VCUG, including
      the catheterization time, was 20 min. No reactions of intolerance to the
      ultrasound contrast agent occurred. DISCUSSION AND CONCLUSIONS: The voiding color
      Doppler US test has evidenced in all patients the presence of the contrast agent
      US in the bladder after the introduction. In 13 patients (77.2%) with presence of
      VUR, the voiding color Doppler US test has established the reflux degree
      confirmed by cystourethrography. The superimposability of the data obtained with
      voiding color Doppler US and VCUG would seem to confirm the importance of this
      new ultrasonographic technique in the diagnosis and staging of VUR.

PMID- 10930767
TI  - Hyperphosphatasemia: report of three cases.
AB  - We report the radiographic findings in three cases of hyperphosphatasemia. Often
      classified as a congenital bone dysplasia, the skeletal manifestations of this
      disorder are diagnostic. These features simulate Paget's disease both
      radiographically and with respect to salient biochemical markers. Typically,
      presentation is at early childhood with skull deformity, refusal to weight bear,
      and bowing of the extremities. Notable radiographic features include bowing of
      the long bones, thickening of the cortex, osteopenia, coarsened trabecular
      pattern, expansion of the medullary cavity, and thickening of the intramembranous
      portion of the calvarium. Histologic features include absence of lamellar bone
      and haversian systems, with thick osteoid seams and increased number of
      osteoclasts. An autosomal recessive pattern of inheritance has been suggested,
      although autosomal dominant varieties have been postulated.

PMID- 10930768
TI  - Magnetic resonance imaging of pyomyositis in 43 cases.
AB  - PURPOSE: To describe the magnetic resonance imaging (MRI) findings in
      pyomyositis. METHODS AND MATERIALS: Forty-three patients with proven muscle
      infection (30 males, 13 females) ranging in age from 14 to 86 years (mean 42
      years) were studied with MRI. The initial clinical diagnose were soft tissue
      infection (n=27), neoplasm (n=12), thrombophlebitis (n=3), and lymphedema (n=1).
      Spin-echo T1- and T2-weighted images were obtained in all cases and STIR sequence
      in 6. Spin-echo T1-weighted images after Gd-DTPA injection were obtained in 16
      cases. The signal intensity findings, the extent of the abnormalities in the soft
      tissue (muscle, fascial and subcutaneous involvement), the presence of fluid
      collections, and the involvement of neighbouring bone and joint were reviewed
      retrospectively. RESULTS: A hyperintense signal on T2-weighted and STIR images
      were detected in all patients. Fluid collections were seen in 21 cases as
      localized areas of hypointensity on the T1-weighted images, and highly
      hyperintense areas on the T2-weighted images. In four patients a rim of high
      signal intensity was seen around the fluid collection on the T1-weighted images.
      On contrast-enhanced T1-weighted images there was diffuse enhancement in the
      patients without fluid collections that was heterogeneous in seven and
      homogeneous in two. After Gd-DTPA all fluid collections showed a central area
      without enhancement and a well-defined enhancing peripheral rim. Involvement of
      adjacent structures included subcutaneous tissue (n=25), bone marrow (n=14),
      fascial planes (n=15) and joints (n=11). CONCLUSION: MRI is useful in the
      assessment of pyomyositis and in determining the location and extension. A
      hyperintense rim on unenhanced T1-weighted images and peripheral enhancement
      after Gd-DTPA are useful for identifying the number, size, and location of soft
      tissue abscesses.

PMID- 10930769
TI  - Quantitative ultrasound of the calcaneus with parametric imaging: correlation
      with bone mineral density at different sites and with anthropometric data in
      menopausal women.
AB  - OBJECTIVE: To prospectively study the relationship of quantitative ultrasound of
      the calcaneus with anthromopometric variables and with bone mineral density (BMD)
      assessed at the level of the calcaneus as well as at other sites. METHOD:
      Osteosonography of the non-dominant calcaneus was performed in 135 menopausal
      women, using a DTU-one device with parametric imaging. Broadband ultrasound
      attenuation (BUA) and speed of sound (SOS) were assessed. BMD of the calcaneus
      (BMDcal) was measured using dual energy X-ray absorptiometry (DXA), in a
      subregion matched with the region of interest for osteosonography. BMD of the
      lumbar trabecular bone was measured using quantitative computed tomography (BMD
      QCT) while the non-dominant hip was studied using DXA, which provided the total
      bone mineral density (BMDhip) and that of the Ward triangle (BMDWard). RESULTS:
      The Pearson correlation coefficients between BUA, SOS and the various
      measurements of BMD ranged from 0.305 (SOS versus BMDhip) to 0.717 (BUA versus
      BMDcal). BMD QCT and BMDWard were found to depend on age, but not on weight or
      height, while BUA, SOS, BMDcal, BMDhip were unrelated to age, but correlated with
      weight (SOS, BMDhip) or with weight and height (BUA, BMDcal). In a multiple
      stepwise regression analysis, age was a significant predictor for BMD QCT, BMD
      hip and BMDWard; BMD QCT, BMDWard and BMDhip admitted BUA as sole predictor,
      while BMDcal was significantly related to both BUA and SOS. CONCLUSION: BUA and
      SOS of the calcaneus, assessed in 135 menopausal women using a parametric imaging
      device, reflected BMDcal, measured with DXA at a matched region of interest, and
      did not decline significantly with age.

PMID- 10930770
TI  - Assessment of the gain transfer function of phosphors for application in medical
      imaging radiation detectors.
AB  - OBJECTIVE: to study various phosphors used in detectors of medical imaging
      systems by the gain transfer function (GTF), defined in terms of X-ray
      luminescence efficiency, light spectrum and modulation transfer function.
      MATERIALS AND METHODS: four phosphor materials, La(2)O(2)S:Tb, Y(2)O(2)S:Tb,
      Y(2)O(2)S:Eu and Y(2)O(3):Eu were used in the form of fluorescent layers prepared
      in the laboratory. The GTF was determined at 30 kVp and 80 kVp X-ray tube
      voltages for various phosphor coating weights. RESULTS: La(2)O(2)S:Tb, which was
      the highest density and effective atomic number phosphor used, was found to
      exhibit the best GTF performance at 80 kVp. At 30 kVp, the yttrium based
      phosphors were found of increased performance. This is mainly due to the
      proximity of the X-ray energy to the K-absorption edge of yttrium at 17 keV.
      Europium activated phosphors were found to perform very well when combined with
      the red sensitive film and the silicon photodiode. CONCLUSION: The GTF may be a
      useful method for comparing and selecting phosphor materials for use in various
      medical imaging applications.

PMID- 10930771
TI  - Quiz case: CPPD crystal deposition disease.

PMID- 10930772
TI  - Preoperative fast MRI of brain tumors using three-dimensional segmented echo
      planar imaging compared to three-dimensional gradient echo technique.
AB  - The purpose of this study was to compare the diagnostic efficacy of a newly
      developed T(1)-weighted three-dimensional segmented echo planar imaging (3D EPI)
      sequence versus a conventional T(1)-weighted three dimensional spoiled gradient
      echo (3D GRE) sequence in the evaluation of brain tumors. Forty-four patients
      with cerebral tumors and infections were examined on a 1.0 T MR unit with 23 mT/m
      gradient strength. The total scan time for the T(1) 3D EPI sequence was 2 min 12
      s, and for a conventional 3D GRE sequence it was 4 min 59 s. Both sequences were
      performed after administration of a contrast agent. The images were analyzed by
      three radiologists. Image assessment criteria included lesion conspicuity,
      contrast between different types of normal tissue, and image artifacts. In
      addition, signal-to-noise and contrast-to-noise-ratio (C/N) were calculated. The
      gray-white differentiation and C/N ratio of 3D EPI were found to be inferior to
      conventional 3D GRE images, but the difference was not statistically significant.
      In the qualitative comparison, lesion detection and conspicuity of 3D EPI images
      and conventional 3D GRE images were similar, but a tow-fold reduction of the
      scanning time was obtained. With the 3D EPI technique, a 50% scan time reduction
      could be achieved with acceptable image quality compared to conventional 3D GRE.
      Thus, the 3D EPI technique could replace conventional 3D GRE in the preoperative
      imaging of brain.

PMID- 10930773
TI  - Quantitation of renal perfusion using arterial spin labeling with FAIR-UFLARE.
AB  - Quantitative perfusion imaging of human kidneys was performed using arterial spin
      labeling MRI with a fast spin echo readout-sequence. Perfusion maps of centrally
      located single slices were obtained in axial and coronal orientations. In ten
      healthy volunteers, the mean value of perfusion was 213+/-55 mL/(100g min) with a
      range from 140 to 319 mL/(100g min). These results are in accordance with
      literature data, considering the fact that FAIR only measures the perfusion
      component normal to the imaging plane. Intra-individual reproducibility errors of
      +/-11% were smaller than the natural interindividual variability of renal
      perfusion (SD = +/- 25%). Perfusion in the cortex was approximately 3-4 times
      higher compared to the medulla. Considering the relatively high resolution of
      2x2x10 mm3, the ability to quantify perfusion, and the lack of ionizing radiation
      and contrast media, this technique should prove useful in diagnosing renal
      pathologies that are associated with reductions in tissue perfusion.

PMID- 10930774
TI  - High-resolution diffusion imaging using phase-corrected segmented echo-planar
      imaging.
AB  - Diffusion magnetic resonance imaging (MRI) was performed with a high-resolution
      segmented echo-planar imaging technique, which provided images with substantially
      less susceptibility artifacts than images obtained with single-shot echo-planar
      imaging (EPI). Diffusion imaging performed with any multishot pulse sequence is
      inherently sensitive to motion artifacts and in order to reduce motion artifacts,
      the presented method utilizes navigator echo phase corrections, performed after a
      one-dimensional Fourier transform along the frequency-encoding direction.
      Navigator echo phases were fitted to a straight line prior to phase correction to
      avoid errors from internal motion. In vivo imaging was performed using electro
      cardiographic (ECG) triggering. Apparent diffusion coefficient (ADC) maps were
      calculated on a pixel-by-pixel basis using up to seven diffusion sensitivities,
      ranging from b = 0 to 1129 x 10(6) s/m(2).

PMID- 10930775
TI  - Noise considerations in the determination of diffusion tensor anisotropy.
AB  - In this study the noise sensitivity of various anisotropy indices has been
      investigated by Monte-Carlo computer simulations and magnetic resonance imaging
      (MRI) measurements in a phantom and 5 healthy volunteers. Particularly, we
      compared the noise performance of indices defined solely in terms of eigenvalues
      and those based on both the eigenvalues and eigenvectors. It is found that
      anisotropy indices based on both eigenvalues and eigenvectors are less sensitive
      to noise, and spatial averaging with neighboring pixels can further reduce the
      standard deviation. To reduce the partial volume effect caused by the spatial
      averaging with neighboring voxels, an averaging method in the time domain based
      on the orientation coherence of eigenvectors in repeated experiments has been
      proposed.

PMID- 10930776
TI  - Minimal gradient encoding for robust estimation of diffusion anisotropy.
AB  - This study has investigated the relationship between the noise sensitivity of
      measurement by magnetic resonance imaging (MRI) of the diffusion tensor (D) of
      water and the number N of diffusion-weighting (DW) gradient directions, using
      computer simulations of strongly anisotropic fibers with variable orientation.
      The DW directions uniformly sampled the diffusion ellipsoid surface. It is shown
      that the variation of the signal-to-noise ratio (SNR) of three ideally
      rotationally invariant scalars of D due to variable fiber orientation provides an
      objective quantitative measure for the diffusion ellipsoid sampling efficiency,
      which is independent of the SNR value of the baseline signal obtained without DW;
      the SNR variation decreased asymptotically with increasing N. The minimum number
      N(0) of DW directions, which minimized the SNR variation of the three scalars of
      D was determined, thereby achieving the most efficient ellipsoid sampling. The
      resulting time efficient diffusion tensor imaging (DTI) protocols provide robust
      estimation of diffusion anisotropy in the presence of noise and can improve the
      repeatability/reliability of DTI experiments when there is high variability in
      the orientation of similar anisotropic structures, as for example, in studies
      which require repeated measurement of one individual, intersubject comparisons or
      multicenter studies.

PMID- 10930777
TI  - On the use of water phantom images to calibrate and correct eddy current induced
      artefacts in MR diffusion tensor imaging.
AB  - The accurate determination of absolute measures of diffusion anisotropy in vivo
      using single-shot, echo-planar imaging techniques requires the acquisition of a
      set of high signal-to-noise ratio, diffusion-weighted images that are free from
      eddy current induced image distortions. Such geometric distortions can be
      characterized and corrected in brain imaging data using magnification (M),
      translation (T), and shear (S) distortion parameters derived from separate water
      phantom calibration experiments. Here we examine the practicalities of using
      separate phantom calibration data to correct high b-value diffusion tensor
      imaging data by investigating the stability of these distortion parameters, and
      hence the eddy currents, with time. It is found that M, T, and S vary only slowly
      with time (i.e., on the order of weeks), so that calibration scans need not be
      performed after every patient examination. This not only minimises the scan time
      required to collect the calibration data, but also the computational time needed
      to characterize these eddy current induced distortions. Examples of how
      measurements of diffusion anisotropy are improved using this post-processing
      scheme are also presented.

PMID- 10930778
TI  - Effects of cell volume fraction changes on apparent diffusion in human cells.
AB  - Diffusion-weighted imaging was used to study the relationship between apparent
      diffusion coefficient (ADC) and cell volume fraction in cell suspensions and
      packed arrays. Cell volume fraction was varied by changing extracellular fluid
      osmolarity (for human glial cells) and by changing cell density (for human glial
      and red blood cells). In packed arrays of glial cells, ADC increased 10% when
      cells shrank and decreased 13% when cells swelled. ADC decreased 34% as cell
      density increased from 0 to 72%. In erythrocyte suspensions, ADC decreased 90% as
      the cell density increased from 0 to 89%. These results agree with theoretical
      predictions.

PMID- 10930779
TI  - Improved phase-contrast flow quantification by three-dimensional vessel
      localization.
AB  - In this paper, a method of three-dimensional (3D) vessel localization is
      presented to allow the identification of a vessel of interest, the selection of a
      vessel segment, and the determination of a slice orientation to improve the
      accuracy of phase-contrast magnetic resonance (PCMR) angiography. A marching-cube
      surface-rendering algorithm was used to reconstruct the 3D vasculature. Surface
      rendering was obtained using an iso-surface value determined from a maximum
      intensity projection (MIP) image. This 3D vasculature was used to find a vessel
      of interest, select a vessel segment, and to determine the slice orientation
      perpendicular to the vessel axis. Volumetric flow rate (VFR) was obtained in a
      phantom model and in vivo using 3D localization with double oblique cine PCMR
      scanning. PCMR flow measurements in the phantom showed 5. 2% maximum error and a
      standard deviation of 9 mL/min during steady flow, 7.9% maximum error and a
      standard deviation of 13 mL/min during pulsatile flow compared with measurements
      using an ultrasonic transit-time flowmeter. PCMR VFR measurement error increased
      with misalignment at 10, 20, and 30 degrees oblique to the perpendicular slice in
      vitro and in vivo. The 3D localization technique allowed precise localization of
      the vessel of interest and optimal placement of the slice orientation for minimum
      error in flow measurements.

PMID- 10930780
TI  - Changes in the liver parenchyma after proton beam radiotherapy: evaluation with
      MR imaging.
AB  - The objective of this study was to describe magnetic resonance (MR) findings with
      a 1.5T imager for hepatic parenchymal changes after proton beam radiotherapy.
      Thirty-two patients who received proton radiotherapy with doses of 50-87 Gy
      underwent MR imaging 1-75 months (mean 22 months) after the start of irradiation.
      Axial T(2), T(1)-weighted imaging, and a dynamic study after a gadolinium
      injection were performed. The irradiated areas showed hypointense in T(1)
      weighted images, hyperintense in T(2)-weighted images, and intense and prolonged
      enhancement on the dynamic study (maximum relative enhancement 441.8%+/-263.3 vs.
      surrounding liver 145.6%+/-67.7, p<0.0001). T(2) values of the irradiated areas
      were 50.6 to 65.8 msec greater than in the surrounding liver (p<0.005). The
      values increased with time, being significantly greater 13 months or longer after
      the beginning of the therapy than after a period of less than 3 months (p<0.05).
      Pathologic examinations (n = 3) indicated that the irradiated areas were composed
      of collapsed lobules with hepatic small vein occlusions, and rich extracellular
      matrices which retained extracellular fluid. MR imaging can demonstrate hepatic
      parenchymal changes after proton beam radiotherapy, and show the changes are
      irreversible.

PMID- 10930781
TI  - Comparison of dual spin echo echo planar imaging (SE_EPI), turbo spin echo with
      fat suppression and conventional dual spin echo sequences for T(2)-weighted MR
      imaging of focal liver lesions.
AB  - The performance of T(2)-weighted spin-echo version of echo planar imaging
      (SE_EPI), conventional spin echo (SE) and fat-suppressed turbo spin-echo
      (TSE_SPIR) sequences for the detection of focal liver lesions was evaluated.
      Twenty patients that were included in our study, had CT examinations prior to the
      MR study and were scheduled for surgery for removal of liver lesions. All
      patients had intraoperative sonographic examinations. Qualitative and
      quantitative analysis of the images was performed. Overall image quality of
      SE_EPI sequences was better than SE (p<0.001) and similar to TSE_SPIR sequences.
      There were fewer motion and ghost artifacts on SE_EPI and TSE_SPIR images
      compared to SE images (p<0.001). Susceptibility artifacts were statistically
      equivalent on SE_EPI and SE images (p<0.001) while chemical shift artifacts were
      equally observed on SE and SE_EPI sequences. Overall image quality of EPI-SE and
      TSE_SPIR sequences was better compared to SE sequences. There was no significant
      difference in the number of lesions detected by each of the three sequences.
      Quantitative analysis showed that liver/lesion contrast-to-noise ratio (CNR) and
      signal-to-noise ratio (SNR) of liver, lesion, spleen was higher on TSE_SPIR
      sequences (p<0.001) while SE_EPI and SE sequences showed non-significant
      differences (p>0.05). SE_EPI sequences of the liver resulted in fewer artifacts
      and shorter acquisition times than SE sequences. They provide a diagnostic
      performance similar to TSE_SPIR and better than that of SE sequences.

PMID- 10930782
TI  - Bayesian estimation of relaxation times T(1) in MR images of irradiated Fricke
      agarose gels.
AB  - The authors present a novel method for processing T(1)-weighted images acquired
      with Inversion-Recovery (IR) sequence. The method, developed within the Bayesian
      framework, takes into account a priori knowledge about the spatial regularity of
      the parameters to be estimated. Inference is drawn by means of Markov Chains
      Monte Carlo algorithms. The method has been applied to the processing of IR
      images from irradiated Fricke-agarose gels, proposed in the past as relative
      dosimeter to verify radiotherapeutic treatment planning systems. Comparison with
      results obtained from a standard approach shows that signal-to noise ratio (SNR)
      is strongly enhanced when the estimation of the longitudinal relaxation rate (R1)
      is performed with the newly proposed statistical approach. Furthermore, the
      method allows the use of more complex models of the signal. Finally, an
      appreciable reduction of total acquisition time can be obtained due to the
      possibility of using a reduced number of images. The method can also be applied
      to T(1) mapping of other systems.

PMID- 10930783
TI  - Application of finite difference time domain method for the design of birdcage RF
      head coils using multi-port excitations.
AB  - A three-dimensional finite difference time domain model was developed where the
      high pass birdcage coil and the imaged object are analysed as a single unit. A
      study was performed comparing linear, conventional quadrature, and four-port
      excitation at 64 MHz and 200 MHz for different coil loadings, namely muscle
      phantoms and an anatomically detailed human head model. A phase array concept was
      utilized to excite the birdcage coil in four ports. Two phase conditions were
      analyzed, the simple fixed phase and the variable phase. At 200 MHz, compared to
      the conventional quadrature drive, the four-port drive reduces the effects of the
      tissue-coil interactions leading to more uniform currents on the coil legs and
      consequently to a better B(1) field homogeneity. Also at 200 MHz, driving the
      coil in four ports provides an SAR distribution with peak values that are
      significantly less than those with linear or quadrature excitations.

PMID- 10930784
TI  - Tissue pH in human kidney transplants during hypothermic ischemia.
AB  - Ex vivo NMR spectroscopy was used to investigate pH in 67 human kidney
      transplants. (1)H and (31)P spectra were recorded at 1.5 T during regular
      hypothermic storage in histidine-tryptophane-alpha-ketoglutarate (HTK) solution.
      Estimations of cytosolic pH from chemical shift differences between inorganic
      phosphate and phosphodiesters and of extracellular pH from the varepsilon1 and
      delta2 protons of histidine were based upon systematic titration studies. The
      possibility to predict acute tubular necrosis (ATN) by measuring pH was compared
      to results obtained with peak area ratios of phosphomonoesters (PME) and Pi and
      of the gamma-phosphorus of nucleoside 5'-triphosphate (gamma-NTP) and Pi.
      Cytosolic pH was 6.86+/-0.10 in kidneys showing immediate post-transplant
      function and 6.84+/-0.10 in those with ATN. Time-dependent studies demonstrated a
      monoexponential pH decay (velocity constant: 0.14+/-0.07 h(-1)). Extracellular pH
      varied between 7.40 and 7.15. Grafts with immediate function showed higher PME/Pi
      (2.24+/-0.57 vs. 1.77+/-0.50, p<0.05) and gamma-NTP/Pi (0.33+/-0.16 vs. 0.16+/
      0.08, p<0.001). Intra- and extracellular pH can be monitored non-invasively
      during hypothermic transplant storage. The pH gradient between both compartments
      provides quantitative information about the buffer capacity of the preservation
      medium. Acidification is not a primary cause of ATN during regular HTK storage.
      The total nucleotide pool is a determinant of the reversibility of ischemic
      injury.

PMID- 10930785
TI  - MR-compatible ventilator for small animals: computer-controlled ventilation for
      proton and noble gas imaging.
AB  - We describe an MR-compatible ventilator that is computer controlled to generate a
      variety of breathing patterns, to minimize image degrading effects of breathing
      motion, and to support delivery of gas anesthesia and experimental inhalational
      gases. A key feature of this ventilator is the breathing valve that attaches
      directly to the endotracheal tube to reduce dead volume and allows independent
      control of inspiratory and expiratory phases of ventilation. This ventilator has
      been used in a wide variety of MR and x-ray microscopy studies of small animals,
      especially for MR imaging the lungs with hyperpolarized gases ((3)He & (129)Xe).

PMID- 10930786
TI  - A comparison of the sensitivity of MRI after double- and triple-dose Gd-DTPA for
      detecting enhancing lesions in multiple sclerosis.
AB  - We compared the number and volume of enhancing lesions detected in patients with
      multiple sclerosis (MS) seen on post-contrast T(1)-weighted scans obtained after
      the injection of different gadolinium-DTPA (Gd) doses. Enhanced magnetic
      resonance imaging (MRI) scans were obtained from 16 patients with relapsing
      remitting or secondary progressive MS on two different occasions separated by an
      interval of approximately 24 h. On the first occasion, enhanced scans were
      obtained 15 min after the injection of a double dose of Gd (0.2 mmol/Kg), on the
      second 15 min after the injection of a triple dose (0.3 mmol/Kg) of Gd. Scans
      were assessed by consensus in a random order by two observers unaware of the dose
      of Gd used. We counted the same 30 enhancing lesions on both double dose and
      triple dose scans from 9 patients. The mean (SD) volumes of enhancing lesions
      were 1.7 (2.7) mL on double dose and 1.9 (3.4) mL on triple-dose scans. This
      difference was not statistically significant. This study demonstrated that double
      dose of Gd has a sensitivity for detecting MS activity similar to that of a
      triple dose, with the advantage of a significant cost saving.

PMID- 10930787
TI  - Preventing aids at $1 a head.

PMID- 10930788
TI  - 'Blair declares war' : the unhealthy state of British drug policy.

PMID- 10930789
TI  - Speed freaks? A literature review detailing the nature and prevalence of dance
      drugs and driving.
AB  - Considerable interest has lately been expressed in motor car driving whilst under
      the influence of drugs. Unlike depressant drugs (e.g. alcohol) dance drugs are
      often perceived to enhance driving skills. The physical effects and the current
      lack of police roadside testing are possible contributing reasons for dance drug
      driving. This paper aims to show through a literature review on the subject, the
      demographics of those involved in dance drug driving and the extent to which
      certain dance drugs are implicated in drug driving incidents. Drug driving is
      found to be highest amongst the 18-35 year age group and more prevalent amongst
      adult males. Prevalence figures for driving under the influence of individual
      drugs are also given. The numbers of people involved in accidents/fatalities and
      testing positive for amphetamine, cocaine and other dance drugs is small.
      Although self-reporting especially of illegal activities is difficult to
      accurately evaluate, most of the reported studies use actual blood/urine samples
      and so can be considered accurate. The literature does not highlight any real
      concerns regarding dance drug driving in terms of prevalence although it does
      highlight the paucity of research in this area, in particular 'Culture E and
      driving'.

PMID- 10930790
TI  - Dual diagnosis - does harm reduction have a role?
AB  - A pragmatic approach to those with a dual diagnosis of mental illness and problem
      drug use accepts that drug and alcohol use is firmly established in this
      population, and aims to minimise and reduce any harms associated with using.
      However, it is evident that we know little about drug using practices and
      knowledge among this group in order to effect such an approach. This paper aims
      to investigate the potential of utilising a harm reduction based approach as an
      alternative to current service responses for those with a dual diagnosis.

PMID- 10930791
TI  - Citizens who inject drugs: the 'Fitpack' study.
AB  - Most injecting drug users have never been in drug treatment yet much research is
      done on samples with high treatment rates drawn from agency and peer recruited
      populations. This study accessed drug injectors with little or no prior drug
      treatment, described their characteristics, BBVI risk behaviours and feedback on
      services. Its results challenge some stereotypes about citizens who inject drugs.
      A sample of 511 'hidden' drug injectors, of whom only 28.7% had any specialist
      drug treatment agency contact, completed a questionnaire which was distributed
      with 'Fitpack' needle packs sold through community pharmacies in WA. The mean age
      of respondents was 26.2 years, 43.4% were women, 44.3% were living with their
      sexual partner, 41.7% were parents, and 46.4% were employed, mostly in full time
      work. In the previous month 61.2% had injected less frequently than daily. The
      study accessed a diverse group of drug injectors not typically seen in agency and
      peer recruited research. They provided useful feedback about how harm reduction
      strategies among injectors can be improved. However, they also reported higher
      rates of injecting and sharing than found previously in traditionally recruited
      samples of injectors which suggests there is no room for complacency regarding
      the potential for blood-borne viral infection (BBVI) transmission in this group.

PMID- 10930792
TI  - Feasibility in needle exchange programme: an evaluation of a pilot programme in
      Catania, Sicily.
AB  - INTRODUCTION: Intravenous drug use (10 V) is a primary transmission route for HIV
      and other blood borne disease. A criminal approach to illicit drug use leads to
      aggressive attitudes towards drug users and forces them underground, thus
      hindering their access to Health Service outlets. A 6-month pilot Needle Exchange
      Programme was set up in Catania, with the aim of reducing the negative effects
      and consequences of drug use, preventing the spread of blood borne diseases by
      encouraging the use of clean needles and reduction of needle sharing. To
      establish contact with the hidden population of the city's, intravenous drug
      users (IDUs) and promote condom use and safer sex. METHOD: An equipped camper was
      parked daily in two of the city's main public squares according to a preset
      timetable, morning and afternoon. A flexible needle exchange policy, i.e. free
      clean needles given out regardless of those returned, was adopted as a strategy
      considered necessary in order to, ensure maximum user-friendliness. Safer
      shooting information leaflets were given out alongside material for the correct
      use of the condom and condoms. RESULT: The number of IDUs, contacted who had
      previously been referred to a National Health Service Drug Unit (Ser.T.) and not,
      and number of syringes exchanged were low but increased month by month.
      CONCLUSION: Future projects should be undertaken after building up, a
      collaborative network between Street Unit and local courts; the city police
      force; social service outlets; hospitals and other health outlets; Ser.T. units
      and local pharmacies. In the light of our current experience, the one to one
      strategy instead to the flexible strategy could lead to stricter adherence to
      harm reduction strategies amongst IDUs.

PMID- 10930793
TI  - Challenges and pitfalls of mass-screening in the European union.

PMID- 10930794
TI  - Recommendations on cancer screening in the European union. Advisory Committee on
      Cancer Prevention.

PMID- 10930795
TI  - Achievements and future of chemotherapy.
AB  - Although surgery and radiotherapy result in a cure in 40% of all cancer patients,
      the remaining 60% of the patients die as a result of metastatic disease. For
      those patients cancer has to be considered as a systemic disease and cure from
      cancer will likely come from some type of systemic treatment. This article gives
      a brief overview of the achievements in the development of chemotherapy over the
      last 50 years and the new potential targets for further drug development.

PMID- 10930796
TI  - Randomised trial of paclitaxel versus doxorubicin as first-line chemotherapy for
      advanced breast cancer: quality of life evaluation using the EORTC QLQ-C30 and
      the Rotterdam symptom checklist.
AB  - The aim of the study was to compare the quality of life (QL) of patients treated
      with single-agent paclitaxel versus doxorubicin as first-line chemotherapy for
      advanced breast cancer. 331 patients with advanced breast cancer were randomised,
      with 294 eligible for analysis. Patients completed both the EORTC QLQ-C30
      questionnaire and the Rotterdam Symptom Checklist (RSCL) with six additional
      items, at baseline and after the third, fifth and seventh cycles of chemotherapy.
      A significant difference in progression-free survival in favour of doxorubicin
      caused a bias in the data with differences in expected completion rates of
      questionnaires beyond cycle three. Therefore, statistical comparisons were
      performed only for the first three cycles. Baseline compliance was 64% and 61%
      for the QLQ-C30 and RSCL questionnaires, respectively. Doxorubicin was associated
      with significantly more nausea/vomiting (P=0.001), loss of appetite (P=0.010) and
      a greater burden of disease and treatment (P=0.044), but with less bone pain
      (P=0.042) and rash (P=0.045) than paclitaxel. Both treatments were associated
      with improved emotional function and reduction in psychological distress at cycle
      3. Longitudinal data suggested that doxorubicin was associated with less pain,
      specifically bone pain. Doxorubicin was more active but may have had more side
      effects during the first three cycles. Long-term QL outcomes could not be
      assessed.

PMID- 10930797
TI  - Identification and interpretation of clinical and quality of life prognostic
      factors for survival and response to treatment in first-line chemotherapy in
      advanced breast cancer.
AB  - The aim of the project was to identify clinical and quality of life (QL) factors
      that together predict survival and response to chemotherapy in advanced breast
      cancer. Potential prognostic factors were studied in 187 women with baseline QL
      data from a trial of paclitaxel versus doxorubicin as first-line chemotherapy.
      Demographic and clinical factors studied were age, performance status, dominant
      site of disease and preceding disease-free interval (DFI). Factors from the EORTC
      QLQ-C30 were all function scales, fatigue, nausea/vomiting, pain, dyspnoea,
      insomnia, loss of appetite and global QL. The proportional hazards regression
      model with stratification for treatment, and the logistic regression model
      adjusting for treatment arm were used for univariate and multivariate analyses of
      survival and response to treatment, respectively. For survival, multiple sites of
      visceral disease, pain, global QL and fatigue were significant prognostic factors
      in the univariate analysis. The final multivariate model predicted poor survival
      with multiple sites of visceral disease (P=0.003), DFI </=2 years (P=0.026) and
      pain (P=0.003). For response, age, dyspnoea, fatigue and global QL were
      significant predictive factors in the univariate analysis. The final multivariate
      model for response selected DFI (P=0.009), multiple sites of visceral disease
      (P=0.037) and dyspnoea (P=<0.001) using forward selection, but model instability
      was indicated by the inclusion of fatigue and emotional function in the final
      model when backward selection was used. In addition to known clinical factors,
      patient-assessed QL variables appear to be prognostic for survival and response
      to chemotherapy in women with advanced breast cancer. However, identification of
      prognostic factors from responses to questionnaires may be unstable, and their
      reliability and clinical utility should be tested prospectively.

PMID- 10930798
TI  - Refined deletion mapping in sporadic breast cancer at chromosomal region 8p12-p21
      and association with clinicopathological parameters.
AB  - We have further refined the loss of heterozygosity (LOH) pattern on the human
      chromosomal region 8p12-p21 using 15 well characterised microsatellite markers in
      a panel of 50 breast carcinomas. The allelic loss pattern of these tumours
      suggests the presence of five commonly deleted regions on 8p12-p21. The most
      commonly deleted region was located between markers D8S1734 and D81989, spanning
      a distance of approximately 3 cM and reaching 56% LOH at locus NEFL. LOH at 8p12
      p21 was significantly correlated with large tumour size (T>5 cm). Patients with
      the age at diagnosis of breast cancer between 45 and 55 years showed
      significantly more LOH than patients older than 55 years or younger than 45
      years. No correlation was observed between 8p12-p21 alterations and histological
      tumour type, grade and the presence of lymph node metastases.

PMID- 10930799
TI  - Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle
      against mesothelioma? The Institut Gustave Roussy experience with chemotherapy
      and chemo-immunotherapy in mesothelioma.
AB  - The aim of this study was to review the experience of the Institut Gustave Roussy
      in 163 patients with malignant mesothelioma over a 9-year period. Data from seven
      consecutive prospective trials, four of chemo-immunotherapy and three of
      chemotherapy were reviewed. The rationale, methods and results of these trials
      are summarised and discussed. 98 patients were included in four phase II trials
      of chemo-immunotherapy whose common denominator was a combination of cisplatin
      and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly
      cisplatin combined with alpha-interferon yielded the highest response rate but
      the toxicity of this regimen was considered unacceptable. Neither higher doses of
      alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen
      were able to enhance the activity of this combination. 18 patients were included
      in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95%
      confidence interval (CI): 0-24) and toxicity was also significant. This regimen
      was, therefore, considered ineffective. Of 17 patients with mesothelioma included
      in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a
      partial response. Responses were seen even in cisplatin-refractory mesothelioma.
      Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3
      mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity
      with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient
      regimen is acceptable (no significant haematological toxicity and no alopecia)
      and compares favourably with that of our previous regimens. The final results
      concerning response and survival are required to confirm the efficacy of this
      combination. The preliminary results of two studies suggest promising activity
      with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The
      efficacy/toxicity ratio of this combination compares favourably with that of our
      previous chemotherapy and chemo-immunotherapy regimens.

PMID- 10930800
TI  - Economics and health-related quality of life in antiemetic therapy:
      recommendations for trial design.
AB  - Emesis (nausea and vomiting) is one of the most important toxicities associated
      with chemotherapy. Although it is not life threatening, it has a major impact on
      a patient's health-related quality of life (HRQL) and overall response to
      chemotherapy. New antiemetics are expensive and well-conducted comparative health
      economic studies are rare. The aim of the study was to review the literature in
      the area of chemotherapy-induced emesis in cancer patients and to offer
      recommendations for the inclusion of these outcomes in the design of clinical
      trials for new antiemetic therapies. The economic literature was reviewed based
      on methodological standards for economic evaluation. Many studies did not comply
      with standards, specifically with regard to the choice of alternatives, chosen
      perspective, setting, type of emesis, measurement of costs and defining outcomes
      (including health-related quality of life). These issues are described for each
      study and recommendations for trial design are presented. The role of economic
      data is to support decision making in choosing between competing antiemetic
      therapies. It is the combination of clinical outcomes, costs and health-related
      quality of life, which will allow treating physicians to comprehensively assess
      the relative value of antiemetic therapies and to provide the most cost-effective
      therapy for their patients.

PMID- 10930801
TI  - Forewarned is forearmed--benefits of preparatory information on video cassette
      for patients receiving chemotherapy or radiotherapy--a randomised controlled
      trial.
AB  - A series of UK and European audits have revealed that a high proportion of
      patients remain dissatisfied with the information they received following a
      diagnosis of cancer. Additional educational aids are often required to facilitate
      the consent process, and our previous work showed a high level of acceptability
      for video-directed information for this purpose. In this study a
      multidisciplinary team of health professionals worked with patients, a
      documentary film company and experienced television personalities to produce an
      information film. The aim of this study was to assess the benefits of receiving a
      cassette to take home following the first consultation and this was evaluated in
      a randomised multicentre controlled study among 220 patients receiving
      chemotherapy or radiotherapy over a 6-month period. There was a significant
      correlation between satisfaction and reduced treatment-related anxiety overall.
      In the video group, the mean Hospital Anxiety and Depression (HAD) anxiety score
      was significantly lower during treatment compared with the non-video group (4.6+/
      3.7 (range: 0-18) versus 7.4+/-5.2 (range: 0-20), Chi square test P=0.001).
      Likewise, the mean HAD depression scores were also significantly lower in the
      patients prepared for the side-effects of treatment with the video (2.9+/-2.9
      (range: 0-13) versus 5.3+/-4.7 (range: 0-21) Chi square test P=0.001). 81% felt
      the video was helpful, only 5% of patients felt this extra information was
      worrying. Well designed video cassettes should be regarded as a useful additional
      information strategy, within routine oncology practice.

PMID- 10930802
TI  - Assessment of percutaneous fine needle aspiration cytology as a technique to
      provide diagnostic and prognostic information in neuroblastoma.
AB  - The International Neuroblastoma Staging System (INSS) criteria for diagnosis
      requires an unequivocal pathological diagnosis and favours the identification of
      prognostic markers in the samples. Surgical biopsies of the primary tumour and
      bone marrow (BM) sampling in metastatic disease constitute the major sources of
      tumour material for the laboratory. We analysed the possibility of percutaneous
      fine needle aspiration cytology (FNAC) constituting an alternative procedure to
      the conventional technique of sampling of the primary tumour in children with
      advanced neuroblastoma. From July 1987 through July 1998, 64 consecutive children
      suspected of having advanced neuroblastoma and referred to our institution
      underwent percutaneous FNAC of deeply located tumours. FNAC was performed using
      22-gauge needles under ultrasound guidance, before any chemotherapy and within
      the first days following admission. No complication occurred after FNAC. The
      median number of the extracted tumour cells was 2.3x10(6) (range: 0-40.6x10(6)).
      Cytology analysis was possible in 59/64 cases (92%) and immunocytochemistry in
      56/64 (88%) allowing confirmation of the diagnosis. N-Myc analysis was available
      in 46/64 (72%). In addition, the presence of a partial deletion of chromosome 1p
      (del 1p) was assessed, since 1992, in 24/47 cases (51%), where enough cells were
      available. FNAC of deeply located advanced neuroblastoma is safe and information
      is available in a few hours after admission. The provided material is reliable
      for confirmation of diagnosis and analysis of biological prognostic markers in
      the majority of cases. More invasive tumour sampling procedures are required only
      in selected cases.

PMID- 10930803
TI  - Analysis of the fragile histidine triad (FHIT) gene in lobular breast cancer.
AB  - The fragile histidine triad (FHIT) gene is a candidate tumour suppressor gene in
      breast and other cancers. We investigated deletions within the FHIT gene in
      lobular breast cancer and found that 16% of cases showed loss of heterozygosity
      (LOH) within the gene. We compared LOH within FHIT in lobular and ductal breast
      tumours and found a significant association between LOH at FHIT and the ductal
      histological type (P<0.001). To determine whether genomic alteration of the FHIT
      gene in lobular breast cancer leads to Fhit inactivation we have assessed the
      level of Fhit expression by immunohistochemical detection and determined that 27%
      (15 of 55) consecutive sporadic lobular tumours showed negative or reduced Fhit
      expression. A significant association was found between LOH at the FHIT gene and
      reduced Fhit expression in lobular and ductal tumours (P=0.025 and P=0.001,
      respectively). Thus, genetic alterations within the FHIT gene, leading to loss of
      Fhit protein, may play an important role in the carcinogenesis of a significant
      number of sporadic lobular breast cancers, even though the apparent frequency of
      genomic alterations within the gene is lower than in ductal breast cancer.

PMID- 10930804
TI  - Efficacy and toxicity profile of oral topotecan in a panel of human tumour
      xenografts.
AB  - On the basis of their mechanism of action (cell killing during DNA replication)
      and the potential reversibility of the drug effects, protracted therapy with
      camptothecins is reported to provide optimal antitumour effects. Furthermore,
      oral administration may be a useful modality for optimisation of treatment. The
      aim of this study was to compare the therapeutic profile of topotecan given
      orally or intravenously in human tumours xenografted into athymic nude mice. The
      drug topotecan was given according to an intermittent (every fourth day, four
      times) or daily (qdx5/weeklyx5-10 weeks; only orally) schedule. Tumour growth
      inhibition and persistence of drug effects were assessed and compared with
      untreated mice. In a panel of seven tumour xenografts, oral topotecan was at
      least as effective on three and significantly more effective on four tumours.
      Using the intermittent schedule, the maximum tolerated dose (MTD) was comparable
      for the two routes (15 mg/kg), but the toxicity profile suggested a better
      tolerability in terms of lethal effects after oral administration. The daily oral
      treatment of low drug doses allowed a higher cumulative dose to be delivered with
      improved antitumour efficacy (2/10 cured in a large cell lung cancer) and no
      evidence of toxicity. In spite of the low bioavailability of oral topotecan
      (23.5%), the persistent plasma levels of the drug suggest that the time of
      exposure to the drug is more critical than the plasma concentrations for
      antitumour efficacy. This interpretation is consistent with the increased
      efficacy of prolonged daily treatment with low-dose levels. The results may have
      implications for the future design of clinical studies.

PMID- 10930805
TI  - Modulation of drug resistance by alpha-tubulin in paclitaxel-resistant human lung
      cancer cell lines.
AB  - Beta(beta)-tubulin isotype variation has recently been implicated in the
      modulation of resistance to paclitaxel in human lung cancer cells and in primary
      human ovarian tumour samples. Whether alpha-tubulin is involved in drug
      resistance has not been reported. We have generated a paclitaxel-resistant cell
      line (H460/T800) from the sensitive human lung carcinoma parental cell line NCI
      H460. The resistant cells are more than 1000-fold resistant to taxol and
      overexpress P-glycoprotein. Interestingly, H460/T800 cells also overexpress alpha
      and beta-tubulin as detected by Western blot analysis. From Northern blot
      analysis, the mechanism of tubulin overexpression appears to be post
      transcriptional. To understand whether alpha-tubulin plays a role in drug
      resistance, we transfected antisense human kalpha1 cDNA construct into the
      H460/T800 paclitaxel-resistant cells. The antisense clones displayed a reduced
      alpha-tubulin expression, and the cells were 45-51% more sensitive to paclitaxel
      and other known antimitotic drugs, compared with vector transfected controls.
      Complementary experiments of transfecting the sense kalpha1 cDNA into H460 cells
      conferred a 1.8- to 3.3-fold increase in the IC(50) of several antimitotic
      agents. Our study suggests that alpha-tubulin is one of the factors that
      contributes to drug resistance.

PMID- 10930806
TI  - Evaluation of the efficacy of potential antineoplastic drugs on tumour metastasis
      by a computer-assisted image analysis.
AB  - Computerised image analysis, performed on histological sections of (C57BL6/N)
      mouse lungs that had been intravenously (i.v.) injected with B16-F10 melanoma
      cells was used to develop a novel method to quantify the efficacy of potential
      antineoplastic drugs. This procedure allowed the evaluation of the rate of
      inhibition of growth and the anti-invasive capability of new molecules, thus
      resulting in more accurate data than that obtained from common macroscopical
      counting of surface metastatic foci. Several morphological parameters can be
      measured by this method: the percentage of tissue area occupied by metastases,
      which accounts for tumour implantation into the organ; the growth index, related
      to the size of the metastases, and the invasion index, related to the frequency
      of foci. These morphometric data were found to be correlated to the levels of
      lung hydroxyproline and transglutaminase activity, well known markers of tumour
      invasion and cell differentiation, respectively. The main objective of this
      computerised procedure was to evaluate how the tumour cell is affected in the
      host by the drug under investigation. The use of the method is exemplified by an
      analysis of the antitumour activity of some methylxanthines.

PMID- 10930807
TI  - Influence of schedule of administration on methotrexate penetration in brain
      tumours.
AB  - The influence of the administration schedule (intravenous (i.v.) bolus versus
      i.v. infusion) on the pharmacokinetics of methotrexate (MTX) in plasma and
      extracellular fluid (ECF) of a brain C6-glioma was investigated in rats. MTX
      concentrations were determined by high performance liquid chromatography (HPLC)
      ultraviolet radiation (UV). MTX (50 mg/kg) was administered by i.v. bolus or i.v.
      infusion (4 h). Concentration-time profiles were fitted to a two-compartment open
      model. Maximum MTX concentrations ranged between 178 and 294 microgram/ml (i.v.
      bolus), and between 11 and 24 microgram/ml (i.v. infusion) in plasma. MTX rapidly
      entered the tumour tissue although its concentrations in the ECF were much lower
      than those observed in plasma for both modes of administration. In spite of an
      important interindividual variability, AUC(ECF) was approximately 5-fold higher
      and mean MTX penetration in tumour ECF (AUC(ECF)/AUC(Plasma)) was approximately 3
      fold higher after i.v. bolus than after i.v. infusion administration. These
      results indicate that i.v. bolus administration schedules promote MTX delivery in
      brain tumour tissue.

PMID- 10930808
TI  - Human papilloma virus status and chromosomal imbalances in primary cervical
      carcinomas and tumour cell lines

PMID- 10930809
TI  - Meta-analysis of studies on breast cancer risk and diet. the role of fruit and
      vegetable consumption and the intake of associated micronutrients

PMID- 10930810
TI  - Anticoagulation factors as predictors of transplant-associated coronary artery
      disease.

PMID- 10930811
TI  - Considerations regarding the contributions of B cells to chronic allograft
      rejection in experimental animal models.

PMID- 10930812
TI  - Early outcome of initiating amiodarone for atrial fibrillation in advanced heart
      failure.
AB  - BACKGROUND: Little information exists about the early outcomes of initiating
      amiodarone for atrial fibrillation in patients with advanced heart failure. This
      study assessed the initial rate of success and complications of amiodarone
      therapy initiated for patients with atrial fibrillation during hospitalization
      for heart failure. METHODS: We reviewed medical records for 37 consecutive
      patients with left ventricular ejection fractions </=40% who underwent initiation
      of amiodarone for atrial fibrillation during hospitalization on a heart failure
      service. RESULTS: Atrial fibrillation was present in 35 (95%) and atrial flutter
      in 2 (5%), with mean duration of 30 months. New York Heart Association class was
      3.1 (+/-1.1). Left ventricular ejection fraction was 24% +/- 7%. All patients had
      received oral amiodarone with an initial dose of 1.2 +/- 0.2 g/day.
      Bradyarrhythmia led to discontinuation of digoxin in 12 (32%) patients and to
      permanent pacemaker placement in 7 (19%) patients. Conversion to sinus rhythm
      occurred spontaneously in 2 patients and after electrical cardioversion in 26
      patients, for an initial success of 76%. After a median follow-up of 9.5 months,
      21 of 37 (57%) patients remained in sinus or atrial-paced rhythm. Amiodarone
      complications occurred after discharge in 5 (14%) patients, 4 with
      hypothyroidism. CONCLUSIONS: Amiodarone with electrical cardioversion has a high
      initial success rate for treatment of atrial fibrillation in patients with heart
      failure with advanced systolic dysfunction. The major early side effect was
      bradyarrhythmia, frequently requiring discontinuation of digoxin or permanent
      pacemaker placement.

PMID- 10930813
TI  - Cardiac troponin I as diagnostic and prognostic marker in severe heart failure.
AB  - BACKGROUND: Cardiac cell death has been shown to occur in heart failure and has
      been implicated as one of the mechanisms responsible for progression of the
      disease. Cardiac Troponin I (cTnI) represents a highly sensitive marker for
      myocardial cell death. Based on previous studies reporting that cTnI may be
      detected in patients with heart failure, we evaluated the clinical correlates and
      prognostic implications of detectable cTnI in a consecutive series of patients
      with severe heart failure. METHODS: Thirty-four patients were examined. Upon
      admission, we measured serum levels of cTnI by conventional immunoenzymatic assay
      (Stratus Dade II). According to the results of this assay, patients were divided
      into 2 groups, based on the presence (cTnI+) or absence (cTnI-) of detectable
      cTnI. These 2 groups were compared by non-parametric analysis for their clinical
      characteristics, instrumental findings, and short-term outcome. RESULTS: The
      cTnI+ group included 10 patients (29%) with a mean serum cTnI of 0.7 +/- 0.3
      ng/ml. Compared with the cTnI- group, these patients had significantly lower left
      ventricular ejection fractions (20% +/- 5% vs 26% +/- 7%, p = 0.023) and a trend
      for higher systolic pulmonary artery pressure (59 +/- 17 mm Hg vs 49 +/- 13 mm
      Hg, p = 0.08). In cTnI+ patients, the correlation between cTnI levels upon
      admission and ejection fraction was r = -0.530 (p = 0.11). We found ischemic
      etiology was equally present in the 2 groups, whereas we never found histologic
      signs of acute myocarditis. Other clinical characteristics (functional class,
      daily diuretic dose, need for intravenous inotropes) were not statistically
      different in the 2 groups. In cTnI+ patients who improved after admission, cTnI
      became undetectable after a few days; in patients with refractory heart failure
      who were hospitalized until death, cTnI persisted in detectable levels throughout
      the observation period. Using the Cox proportional hazard model, a positive cTnI
      was the most powerful predictor of mortality at 3 months (p = 0.013; hazard ratio
      6.86; 95% confidence interval 1.32 to 35.4). CONCLUSIONS: These observations
      suggest that cTnI is detected in the blood of 25% to 33% of patients with severe
      heart failure; its presence may help to identify a high-risk sub-group who faces
      very poor short-term prognosis.

PMID- 10930814
TI  - Non-invasive cardiac allograft monitoring: the graz experience.
AB  - Based on previous reports by our group, initial studies on non-invasive cardiac
      graft monitoring have been presented recently. In this study we define new
      parameters to monitor rejection and infection after heart transplantation (HTX)
      the ventricular evoked response (VER) T-slew rate parameter is defined as the
      maximum negative slope in the descending part of the repolarization phase of the
      VER. We calculated the VER duration parameter in milliseconds and defined it as
      the time between the pacemaker spike and the cross-over of the baseline, with the
      slope line used to calculate the VER T-slew rate. During the HTX procedure, we
      implant wide-band telemetric pacemakers and fractally coated, epimyocardial
      electrodes (Physios CTM 01 and ELC 54-UP, Biotronik; Berlin, Germany). During
      each follow-up and on biopsy days, intramyocardial electrogram sequences were
      obtained and sent via the Internet to the central data-processing unit in Graz.
      We scored the infection status of the patients before data acquisition. The VER
      parameters were automatically calculated and send back within a few minutes. We
      prospectivly compared 1,613 follow-ups from 42 patients with biopsy
      (International Society of Heart and Lung Transplantation grading) and infection
      classification. The VER duration parameter did not change during rejection;
      however, we found an increase during clinically apparent infection. The VER T
      slew rate parameter was lower during rejection grade 2 or higher, as well as
      during clinically apparent infection. The negative predictive value to rule out
      rejection was 99%. Our results indicate that rejection and infection cause
      different, reproducible effects on the electrical activity of the transplanted
      heart. Non-invasive cardiac graft monitoring may reduce the need for surveillance
      biopsies and may offer a tool to optimize immunosuppressive therapy after HTX.

PMID- 10930815
TI  - Lung nodular lesions in heart transplant recipients.
AB  - To describe the characteristics and etiology of lung nodules after heart
      transplantation (HT). During a 6-year period 147 patients received HT and 130
      survived more than 1 week. Nodular lesions were demonstrated after HT in 13
      patients (10%). Median age was 53 years, and all patients were male. Nodules were
      detected 23 to 158 days after HT (median, 66 days). An etiologic diagnosis was
      made in all but 1 case: Aspergillus (5), Nocardia-Rhodococcus (4), and
      cytomegalovirus (CMV) (3). Previous severe infection was present in 50% of the
      patients and rejection in 33% (75% with nocardiosis). Initially all patients with
      Nocardia but only 1 patient with aspergillosis were asymptomatic. The most common
      symptoms were fever (67%) and cough (50%). Central nervous system (CNS)
      involvement appeared in only one Aspergillus-infected patient. An average of 1.8
      diagnostic procedures per patient were performed. Median time to establish a
      diagnosis was 8 days (0 to 24). Median hospital stay was 36 days and reached 60
      in patients with Aspergillus. No patient died, although aspergillosis, which must
      be suspected in the presence of dyspnea, pleuritic pain, and CNS symptoms, caused
      the highest morbidity. Overall diagnostic yield was 60% for transtracheal
      aspiration, 70% for bronchoalveolar lavage, and 75% for transthoracic aspiration.
      Ten percent of HT patients developed lung nodules that were mainly caused by
      Aspergillus, Nocardia, and CMV. The time of appearance and some clinical
      manifestations may suggest the etiology and may help in the empirical treatment.

PMID- 10930816
TI  - Reversal of metallothionein expression is different throughout the human
      myocardium after prolonged left-ventricular mechanical support.
AB  - OBJECTIVES: We examined the distribution of metallothionein (MT), a stress
      inducible protein, and the cardiomyocyte diameter in human hearts after left
      ventricular assist device (LVAD) support. BACKGROUND: Remodeling in end-stage
      heart failure is characterized by myocyte hypertrophy and alterations of several
      inducible proteins. LVADs used as a bridge to cardiac transplantation unload the
      left ventricle and may lead to a reversal of the remodeling, but little is known
      about the pathophysiology of this process. METHODS: The immunoreactivity for MT
      and the cardiomyocyte diameter was analyzed in left-ventricular tissue specimens
      of 17 patients with end-stage heart failure before and after LVAD support.
      RESULTS: MT positive cells were mainly located sub-endocardially in vacuolized
      cardiomyocytes and in small vessels throughout the myocardium. During LVAD
      support, MT-positive myocytes decreased in the sub-endocardial (p < 0.008) and
      sub-epicardial region (p < 0.003), MT-positive vessels decreased similarly (p <
      0.003). Cardiomyocyte diameter decreased significantly only in the sub
      endocardium (p < 0.03). Hearts of patients supported longer than 88 days (=
      median) showed substantially lower MT reactivity at the time of LVAD explantation
      as compared to patients supported less than 88 days. CONCLUSION: Our results
      suggest that unloading of the left ventricle during prolonged LVAD support leads
      to regression of cellular hypertrophy and a decrease of MT expression. The
      preferential reduction of MT-positive vacuolized cardiomyocytes in the sub
      endocardium is comparable with the concept of greatest reduction of wall stress
      in this area of the myocardium and may be due to the improvement of myocardial
      blood flow and the energy balance.

PMID- 10930817
TI  - Biphasic response after brain death induction: prominent part of catecholamines
      release in this phenomenon.
AB  - BACKGROUND: The physiopathology of hemodynamic instability that occurs after
      brain death remains unknown. The aim of this study was to examine the initial
      response to brain death induction. METHODS: After anesthesia and monitoring, 16
      pigs were randomized into a control group (C, n = 8) and a brain death group (BD,
      n = 8). We inflated a subdural catheter balloon to induce brain death. We
      analyzed hemodynamic and plasmatic biochemical data for 180 minutes after brain
      death induction. Energetic compounds were measured. We expressed the results in
      comparison with the C group. RESULTS: The C group remained stable. One minute
      after brain death, the Cushing reflex appeared, with a hyperdynamic response to
      plasma catecholamines levels increasing (norepinephrine and epinephrine, 3.1
      fold, p = 0. 02, and 3.8-fold, p = 0.07, respectively). After a return to
      baseline, we recorded a second hyperdynamic profile 120 minutes later. At this
      time, a second peak of catecholamines appeared (6. 3-fold, p = 0.04, and 9.1
      fold, p = 0.02, concerning norepinephrine and epinephrine). At the same time, we
      observed brief myocardial lactate production (+175%, p < 0.01), with a rise of
      troponine I (+64%, p = 0.03). The energetic index was similar in both groups: 0.
      85 (+/-0.02) in the C group vs 0.87 (+/-0.02) in the BD group. CONCLUSIONS: In
      this model, biphasic plasmatic catecholamine release appears to primarily explain
      the physiopathology of the hemodynamic response to brain death induction.

PMID- 10930818
TI  - Role of neural and humoral factors in hyperdynamic reaction and cardiac
      dysfunction following brain death.
AB  - BACKGROUND: Although hemodynamic instability and cardiac dysfunction after brain
      death are reported in the potential organ donor, the underlying mechanisms, for
      example, neurohumoral changes, myocardial injury, and altered loading conditions,
      have not been differentiated in clinical and experimental settings. In the
      present study, we performed a load-independent analysis of cardiac function,
      focusing on the influence of brain death-associated neural and humoral factors.
      METHODS: In a canine in situ cross-circulated heart model, brain death was
      induced by inflation of a subdural balloon catheter. Preload, afterload, and
      coronary perfusion pressure were kept identical in all hearts throughout the
      experiment. In Group H (humoral factors), the hearts of healthy dogs were
      perfused with blood from brain-dead support dogs (n = 6). In Group N (neural
      factors), the hearts of brain-dead dogs were perfused with blood from healthy
      support dogs (n = 6). In Group H + N (humoral and neural factors), the hearts of
      brain-dead dogs were perfused parabiotically in situ with the animals' own blood
      (n = 6). Systolic and diastolic pressure-volume relationships and coronary blood
      flow were measured. RESULTS: Induction of brain death led to a significant
      hyperdynamic response in all groups, with a maximal reaction in Group H + N
      followed by Group H and Group N. After the initial hyperdynamic phase, cardiac
      function returned to baseline within 15 minutes and remained stable in all groups
      for the 2-hour observation period. CONCLUSIONS: (1) Both neural and humoral
      factors contribute to the initial hyperdynamic reaction after brain death, and
      only in combination do they cause a maximal hemodynamic effect. (2) If loading
      conditions and perfusion pressure are kept constant, no cardiac dysfunction
      occurs after brain death. This indicates that poor cardiac function in the
      potential donor may reflect altered loading conditions and impaired coronary
      perfusion rather than neurohumorally mediated direct myocardial injury.

PMID- 10930820
TI  - Pulmonary vascular resistance and reactivity in children with end-stage
      cardiomyopathy.
AB  - Pulmonary vascular resistance (PVR) and reactivity were compared in 63 children
      with end-stage cardiomyopathy (CM) referred for cardiac transplantation.
      Diagnostic category of CM was the sole determinant of PVR. Compared with other
      patients, children with restrictive CM were younger at diagnosis and had a
      significantly higher pulmonary vascular resistance index (PVRI). Children with a
      baseline PVRI of up to 11.8 units per meter squared (U.m(2)) who showed
      reactivity underwent successful orthotopic cardiac transplantation.

PMID- 10930819
TI  - FK409 ameliorates ischemia-reperfusion injury in heart transplantation following
      12-hour cold preservation.
AB  - OBJECTIVE: FK409 is the first spontaneous nitric oxide donor to increase plasma
      guanosine 3':5'-cyclic monophosphate. We designed this study to investigate
      whether the administration of FK409 during reperfusion ameliorated ischemia
      reperfusion injury and enhanced post-transplant graft function in orthotopic
      heart transplantation following 12-hour cold preservation in a canine model.
      METHODS: We used 10 pairs of adult mongrel dogs, weighing 9.5 to 13.5 kg.
      Following cardiac arrest using cardioplegia, we washed out the coronary vascular
      beds with cold University of Wisconsin solution followed by 12-hour preservation.
      After preservation, we performed orthotopic transplantation. The experimental
      animals were divided into 2 groups. In the FK group (n = 5), FK409 (5
      microg/kg/min) was administered intravenously, beginning 15 minutes before the
      onset of reperfusion and continuing for 45 minutes after reperfusion. In the
      control group (n = 5), saline vehicle was administered in the same manner. Two
      hours after transplantation, we assessed cardiac function, including cardiac
      output, left ventricular systolic pressure (LVP), and the maximum rates of
      positive and negative increase of LVP (+/-LV dP/dt) by comparing the recovery
      rate (%) of the cardiac function of the donor animal. We measured endothelin-1
      levels in blood obtained from a catheter inserted into the coronary sinus 30, 60,
      and 120 minutes after reperfusion. RESULTS: Cardiac output was higher in the FK
      group than in the control group, but the difference was not significant (p =
      0.08). Left ventricular systolic pressure and +/-LV dP/dt were significantly (p <
      0.05) higher in the FK group than in the control group. Endothelin-1 levels were
      significantly (p < 0.05) lower in the FK group than in the control group 30
      minutes after reperfusion. Transmission electron microscopy showed that the basal
      lamina of capillary vessels, glycogen granules, and mitochondrial structure were
      well-preserved in the FK group. CONCLUSIONS: In orthotopic transplantation
      models, FK409 is effective in ameliorating ischemia-reperfusion injury following
      preservation and in enhancing post-transplant cardiac function.

PMID- 10930821
TI  - Balloon-expandable stent placement for superior vena cava-right atrial stenosis
      after heart transplantation.
AB  - Anastomotic Stenoses are well known as a complication of vascular and
      cardiovascular surgical procedures; such a lesion was encountered at the superior
      vena cava-right atrial anastomosis after cardiac transplantation. A balloon
      expandable stent was used to relieve this anastomotic constriction, employing a
      16 mm diameter balloon to deliver a P304 stent. Stent placement resulted in
      complete relief of the patient's symptoms and facilitated the passage of
      bioptomes through the superior vena cava for subsequent biopsy procedures
      following cardiac transplantation.

PMID- 10930822
TI  - Role of statins in the management of dyslipidemia after cardiac transplant:
      randomized controlled trial comparing the efficacy and the safety of atorvastatin
      with pravastatin.
AB  - BACKGROUND: Cardiac transplant patients are at increased risk of dyslipidemia, a
      known pathogenetic factor in chronic rejection. The aim of this study was to
      compare the efficacy and the safety of treatment with atorvastatin (AT) and
      treatment with pravastatin (PV) in a population of dyslipidemic transplant
      patients. METHODS: Thirty-nine transplant patients were randomized to receive a 4
      month cycle of therapy with AT or PV, in a cross-over sequence. We analyzed the
      effects on their lipid profiles using Student t-test for paired data. RESULTS AND
      CONCLUSION: Atorvastatin was significantly more effective than PV in reducing
      total cholesterol (33% vs 21%, p < 0.001), LDL cholesterol (45% vs 30%, p =
      0.001), and triglycerides (24% vs 7.7%, p < 0.001), at lower doses and with
      comparable tolerability and safety.

PMID- 10930823
TI  - Clinical challenges in thoracic organ transplantation: case studies in
      immunosuppressive therapy.

PMID- 10930824
TI  - The protein content in crystals and packing coefficients in different space
      groups.
AB  - A precise way of estimating the packing coefficient, i.e. the ratio between the
      protein and unit-cell volume, or solvent content in protein crystals is given. At
      present, the solvent content is not given for most proteins in the Protein Data
      Bank and in many cases where it is given the values are dubious. The mean density
      of proteins in the crystalline form is around 1.22 g cm(-3), not 1.35 g cm(-3) as
      usually stated. This is equivalent to 19.5 A(3) per non-H atom. A statistical
      investigation of the average protein content and packing coefficient in different
      space groups is presented. The packing coefficients are generally higher in the
      most frequently occurring space groups than in the uncommon space groups. There
      is also a remarkable difference in frequency distribution for enantiomorphous
      pairs of space groups.

PMID- 10930825
TI  - Accurate calculation of the density of proteins.
AB  - On the basis of theoretical calculations, Andersson & Hovmoller have recently
      suggested that the long-established value of 1.35 g cm(-3) for the mean density
      of proteins should be revised to 1.22 g cm(-3) [Andersson & Hovmoller (2000),
      Acta Cryst. D56, 789-790]. To substantiate their assertion, these authors used
      the Voronoi algorithm to calculate the mean atomic volume for 30 representative
      protein structures. The Voronoi procedure requires that atoms of interest be
      bounded on all sides by other atoms. Volume calculations for surface atoms that
      are not surrounded or are only sparsely surrounded by other atoms either are not
      possible or may be unreliable. In an attempt to circumvent this problem,
      Andersson & Hovmoller rejected atoms with calculated volumes that were
      indeterminate or were greater than 50 A(3). In the present study, it is shown
      that this criterion is not sufficiently restrictive to ensure accurate volume
      determinations. When only strictly buried atoms are included in the volume
      calculations using the Voronoi algorithm, the mean density is found to be 1.47 +/
      0.05 g cm(-3). In addition, an alternate procedure based on the Connolly
      algorithm that permits all protein atoms to be included in volume calculations
      gives 1.43 +/- 0.03 g cm(-3) for the mean density of the same set of proteins.
      The latter two calculated values are mutually consistent and are in better
      agreement with the experimental value.

PMID- 10930827
TI  - The structures of deoxy human haemoglobin and the mutant Hb Tyralpha42His at 120
      K.
AB  - The structures of deoxy human haemoglobin and an artificial mutant (Tyralpha42-
      >His) have been solved at 120 K. While overall agreement between these structures
      and others in the PDB is very good, certain side chains are found to be shifted,
      absent from the electron-density map or in different rotamers. Non
      crystallographic symmetry (NCS) is very well obeyed in the native protein, but
      not around the site of the changed residue in the mutant. NCS is also not obeyed
      by the water molecule invariably found in the alpha-chain haem pocket in room
      temperature crystal structures of haemoglobin. At 120 K, this water molecule
      disappears from one alpha chain in the asymmetric unit but not the other.

PMID- 10930826
TI  - Structure of m-carboxyphenyl-alpha-D-galactopyranoside complexed to heat-labile
      enterotoxin at 1.3 A resolution: surprising variations in ligand-binding modes.
AB  - In the quest to develop drugs against traveller's diarrhoea and cholera, the
      structure of the B pentamer of heat-labile enterotoxin (LT) complexed with a new
      receptor-binding antagonist, m-carboxyphenyl-alpha-D-galactopyranoside, has been
      determined. The high resolution obtained for this structure allowed anisotropic
      refinement of the model. It was also now possible to confirm at a near-atomic
      resolution the structural similarity between the B subunits of LT and the closely
      related cholera toxin (CT), including the similarity in deviations of planarity
      of the same peptide unit in LT and CT. The structure of the LT complex clearly
      revealed different conformations for the m--carboxyphenyl moiety of the ligand in
      the five B subunits of LT, while the binding modes of the well defined
      galactopyranoside moieties were identical. In two binding sites the m
      carboxyphenyl moiety displayed no significant electron density, demonstrating
      significant flexibility of this moiety. In a third binding site the m
      carboxyphenyl moiety could be modelled unambiguously into the density. The two
      remaining binding sites were involved in crystal packing contacts and the density
      for the ligands in these two binding sites clearly revealed different binding
      modes, of which one conformation was identical to and one completely different
      from the conformation of m-carboxyphenyl-galactopyranoside in the third subunit.
      The multiple binding modes observed in the crystal may represent the ensemble of
      conformations of m-carboxyphenyl-alpha-D-galactopyranoside complexed to LT in
      solution.

PMID- 10930828
TI  - Genetically crosslinked hemoglobin: a structural study.
AB  - The crystal structures of three recombinant human hemoglobins, rHb1. 0, rHb1.1
      and rHb1.2, have been determined in the deoxy state at 1.8 A resolution. Two of
      the three proteins, rHb1.1 and rHb1.2, contain a genetic fusion of the alpha
      subunits, a one- or two-glycine link, respectively, whereas rHb1.0 does not. The
      glycine crosslinks, localized between one N- and C--termini pair of the alpha
      subunits in the deoxy crystalline state, do not perturb the overall tertiary or
      quaternary or even the local structure of hemoglobin. Therefore, genetic fusion
      to prevent the dissociation of the hemoglobin tetramer, thereby inhibiting renal
      clearance based upon molecular size, is a structurally conservative method to
      stabilize hemoglobin for use as an oxygen-delivery therapeutic.

PMID- 10930829
TI  - Statistical methods for the objective design of screening procedures for
      macromolecular crystallization.
AB  - The crystallization of a new macromolecule is still very much a trial-and-error
      process. As is well known, it requires the search of a large parameter space of
      experimental settings to find the relatively few idiosyncratic conditions that
      lead to diffraction-quality crystals. Crystallographers have developed a variety
      of screens to help identify initial crystallization conditions, including those
      based on systematic grids, incomplete factorial and sparse-matrix approaches.
      These are somewhat subjectively formulated based on accumulated data from past
      crystallization experiments. Ideally, one would prefer as objective a procedure
      as possible; however, that requires objective methods that incorporate a broad
      source of crystallization data. The Biological Macromolecular Crystallization
      Database (BMCD), a repository of all published crystallization conditions, is an
      obvious source of this data. This database has been augmented with a hierarchical
      classification of the macromolecules contained in the BMCD as well as extensive
      data on the additives used with them. A statistical analysis of the augmented
      BMCD shows the existence of significant correlations between families of
      macromolecules and the experimental conditions under which they crystallize. This
      in turn leads to a Bayesian technique for determining the probability of success
      of a set of experimental conditions based on the data in the BMCD as well as
      facts about a macromolecule known prior to crystallization. This has been
      incorporated into software that enables users to rank experimental conditions for
      new macromolecules generated by a dense partial factorial design. Finally, an
      additional advantage of the software described here is that it also facilitates
      the accumulation of the data required for improving the accuracy of estimation of
      the probabilities of success - knowledge of the conditions which lead to failure
      of crystallization.

PMID- 10930830
TI  - AutoDep: a web-based system for deposition and validation of macromolecular
      structural -information.
AB  - This paper describes the design and full implementation of a new concept in data
      deposition and validation: AutoDep (copyright Brookhaven Science Associates LLC).
      AutoDep changes the traditional procedure for data acceptance and validation of
      the primary databases into an interactive depositor-driven operation which almost
      eliminates the delay between the acceptance of the data and its public release.
      The system takes full advantage of the knowledge and expertise of the
      experimenters, rather than relying on the database curators for the complete and
      accurate description of the structural experiment and its results. AutoDep,
      developed by the Protein Data Bank at Brookhaven National Laboratory (BNL) as a
      flexible and portable system, has already been adopted by other primary databases
      and implemented on different platforms/operating systems. AutoDep was introduced
      at BNL in 1996 [see Manning (1996), Protein Data Bank Quart. Newslett. 77, 2
      (ftp://ftp.rcsb. org/pub/pdb/doc/newsletters/bnl/newsletter96jul/newslttr+
      ++.txt); Manning (1996), Protein Data Bank Quart. Newslett. 78, 2 (ftp://ftp.
      rcsb.org/pub/pdb/doc/newsletters/bnl/newsletter96oct/+ ++newslttr.txt)].

PMID- 10930831
TI  - Eigensystem analysis of the refinement of a small metalloprotein.
AB  - The eigenvalues and eigenvectors of the least-squares normal matrix for the full
      matrix refinement problem contain a great deal of information about the quality
      of a model; in particular the precision of the model parameters and correlations
      between those parameters. They also allow the isolation of those parameters or
      combinations of parameters which are not determined by the available data. Since
      a protein refinement is usually under-determined without the application of
      geometric restraints, such indicators of the reliability of a model offer an
      important contribution to structural knowledge. Eigensystem analysis is applied
      to the normal matrices for the refinement of a small metalloprotein using two
      data sets and models determined at different resolutions. The eigenvalue spectra
      reveal considerable information about the conditioning of the problem as the
      resolution varies. In the case of a restrained refinement, it also provides
      information about the impact of various restraints on the refinement. Initial
      results support conclusions drawn from the free R factor. Examination of the
      eigenvectors provides information about which regions of the model are poorly
      determined. In the case of a restrained refinement, it is also possible to
      isolate places where X-ray and geometric restraints are in disagreement, usually
      indicating a problem in the model.

PMID- 10930832
TI  - The geometry of metal-ligand interactions relevant to proteins. II. Angles at the
      metal atom, additional weak metal-donor interactions.
AB  - Geometrical data which could be of relevance in the structure determination,
      structure refinement, assessment or understanding of metalloproteins have been
      extracted from the Cambridge Structural Database (CSD). The CSD contains
      crystallographic data from 'small-molecule' structures determined by X-ray or
      neutron diffraction to an accuracy and precision much better than that of most
      current protein structure determinations. Structures of Mg, Mn, Fe, Cu and Zn
      complexes with ligands whose donor atoms may be only N, O, S or Cl have been
      selected and analysed in terms of the geometry of the metal coordination group -
      octahedral, tetrahedral, tetragonal pyramidal etc. The r.m.s. deviation of all
      the interbond angles around the metal atom provides a measure, delta, of the
      deviation from ideal geometry. Average values of delta are tabulated for the
      different metals in each type of complex. For simple non-chelated complexes of
      Mn, Fe and Zn, distortions of up to 5 degrees in octahedral complexes and 10
      degrees in tetrahedral complexes are found to be normal and seem likely to be a
      consequence of packing effects, ligand bulk or intramolecular effects.
      Substantially larger distortions are found for some other metals and geometries
      and are common for chelated complexes. Brief comments on six-, seven- and eight
      coordinate Ca complexes are included. Tables are also presented showing that for
      four- and five-coordinate complexes of Zn and Cu it is quite common to find
      additional weakly coordinated ligands, usually with N or O donor atoms and with
      M.N,O distances longer than a normal bond length but shorter than a van der Waals
      contact, e.g. in the range 2.4-3.0 A for Zn and 2.6-3.0 A for Cu. Although the
      contributions to bond valency or bonding energy of such interactions may not be
      great, their effect on geometry can be considerable; they can, for example, cause
      much larger distortions of tetrahedral Zn complexes than indicated above.

PMID- 10930833
TI  - Synchrotron X-ray reciprocal-space mapping, topography and diffraction resolution
      studies of macromolecular crystal quality.
AB  - A comprehensive study of microgravity and ground-grown chicken egg-white lysozyme
      crystals is presented using synchrotron X-ray reciprocal-space mapping,
      topography techniques and diffraction resolution. Microgravity crystals displayed
      reduced intrinsic mosaicities on average, but no differences in terms of strain
      over their ground-grown counterparts. Topographic analysis revealed that in the
      microgravity case the majority of the crystal was contributing to the peak of the
      reflection at the appropriate Bragg angle. In the ground-control case only a
      small volume of the crystal contributed to the intensity at the diffraction peak.
      The techniques prove to be highly complementary, with the reciprocal-space
      mapping providing a quantitative measure of the crystal mosaicity and strain (or
      variation in lattice spacing) and the topography providing a qualitative overall
      assessment of the crystal in terms of its X-ray diffraction properties.
      Structural data collection was also carried out at the synchrotron.

PMID- 10930834
TI  - Triple-axis X-ray diffraction analyses of lysozyme crystals.
AB  - High-resolution triple-axis X-ray diffraction techniques have been used to
      monitor the defect structure in hen egg-white lysozyme crystals. Analyses from
      the (440), (12;0) and (160) reflections showed significant differences in the
      intensity distribution around the respective reciprocal-lattice points. This work
      suggests that X-ray diffraction analytical methods developed primarily for
      relatively perfect inorganic crystals can be successfully applied to structurally
      defective macromolecular crystals. The analysis of defects at high angular
      resolution is complicated, however, by the observation that protein crystals lie
      at the convergence of the kinematic (ideally imperfect) and dynamic (ideally
      perfect) treatments of diffraction.

PMID- 10930835
TI  - Increased resolution data from a large unit cell crystal collected at a third
      generation synchrotron X-ray source.
AB  - A third-generation synchrotron source was used to collect data from crystals with
      a very large unit cell. There was an increase in the effective resolution of the
      data from 5 to 3.5 A. Data were collected on crystals of HK97 mature empty
      capsids, space group P2(1), with unit-cell parameters a = 580, b = 625, c = 790
      A, beta = 90.0 degrees. Like other crystals with very large unit-cell dimensions,
      the intensity falls off rapidly as a function of resolution, with a precipitous
      drop beginning at 9 A resolution. Synchrotron data from these crystals were
      previously observed at the CHESS F1 beamline to about 3.5 A resolution, but the
      intensities could not be accurately measured beyond 5 A. In experiments conducted
      at the Advanced Photon Source (APS) beamline 14-BM-C, data from identical
      crystals could be processed to a resolution of 3.5 A. The lifetime of the
      crystals in the beam was increased from one exposure per crystal volume to
      between four and eight exposures per crystal volume. More than 500 images were
      collected in two trips, allowing the extension of the resolution of the data set
      and the structure determination to 3.5 A resolution. Factors in the increased
      resolution may include X-ray flux, beamline geometry and low background scatter.
      These results suggest that other crystals with large unit cells and pronounced
      intensity falloff with resolution may benefit from the use of this or similar
      beamlines.

PMID- 10930836
TI  - Purification and crystallization of the extracellular domain of human neutral
      endopeptidase (neprilysin) expressed in Pichia pastoris.
AB  - Neutral endopeptidase (NEP) is a mammalian zinc metalloprotease involved in the
      inactivation of a wide variety of regulatory peptides such as enkephalins and
      atrial natiuretic factor. The soluble extracellular domain of NEP (sNEP) was
      expressed in the methylotrophic yeast Pichia pastoris. The protein was purified
      to homogeneity and single crystals have been obtained. Enzymatic deglycosylation
      of the enzyme was essential for the production of crystals suitable for X-ray
      analysis for both the NEP-phosphoramidon binary complex and the apo enzyme.

PMID- 10930837
TI  - Crystallization of agglutinin from the seeds of Abrus precatorius.
AB  - Agglutinin protein purified from the seeds of Abrus precatorius has a high
      antitumour activity and was crystallized at room temperature with polyethylene
      glycol 8000 as the precipitant. The agglutinin crystal diffracted to 3.45 A and
      belongs to one of two possible tetragonal space groups, P4(1)2(1)2 or P4(3)2(1)2,
      with unit-cell parameters a = b = 141.91, c = 105.63 A. The asymmetric unit
      contains a heterotetrameric protein molecule of molecular weight 134 kDa and has
      a solvent content of approximately 38%.

PMID- 10930838
TI  - Expression, purification and preliminary crystallographic studies of a
      hyperthermophilic esterase from Archaeoglobus fulgidus.
AB  - An esterase from the hyperthermophilic archeon Archaeoglobus fulgidus has been
      expressed, purified and crystallized in a form suitable for structure analysis.
      The enzyme has a molecular mass of 35 467 Da and shows sequence similarity to
      other esterases known to possess the alpha/beta hydrolase fold. The crystals
      diffract to 2.8 A and belong to space group I222 or I2(1)2(1)2(1), with unit-cell
      parameters a = 155.6, b = 155.0, c = 162.4 A.

PMID- 10930839
TI  - Crystallization and preliminary X-ray diffraction analysis of the mitochondrial
      transcription factor sc-mtTFB from Saccharomyces cerevisiae.
AB  - Eukaryotic mitochondria contain a distinct mini-chromosome. In yeast,
      transcription of the mitochondrial genome is mediated by a nuclear-encoded RNA
      polymerase consisting of a single polypeptide core enzyme and a specificity
      factor termed sc-mtTFB which bears some similarity to bacterial sigma-factors. sc
      mtTFB from Saccharomyces cerevisiae has been cloned, expressed, purified and
      crystallized. The crystals belong to the monoclinic space group C2, with unit
      cell parameters a = 89.7, b = 44.6, c = 98.9 A, beta = 110 degrees. Based on one
      molecule per asymmetric unit, the solvent content is estimated to be 48%. Small
      crystals of dimensions 0.01 x 0.05 x 0.13 mm diffract to at least 2.7 A
      resolution on a rotating-anode X-ray source.

PMID- 10930840
TI  - Crystallization and preliminary X-ray analysis of chondroitin sulfate ABC lyases
      I and II from Proteus vulgaris.
AB  - Chondroitin sulfate ABC lyases (E.C. 4.2.2.4) are broad-specificity
      glycosaminoglycan-degrading enzymes. Their preferred substrates are chondroitin
      sulfate and dermatan sulfate, which are broken down to short oligosaccharides.
      Proteus vulgaris produces two such lyases, ABC lyase I and II, with molecular
      weights of 112-113 kDa. Diffraction-quality crystals of both enzymes have been
      obtained by the hanging-drop vapour-diffusion method. ABC lyase I crystallizes in
      space group P2(1)2(1)2(1), with unit-cell parameters a = 49.3, b = 95.1, c =
      230.0 A, Z = 4, and diffracts to 1.9 A resolution. Crystals of ABC lyase II
      belong to space group P1, with unit-cell parameters a = 64.2, b = 64.3, c = 142.1
      A, alpha = 95.7, beta = 98. 1, gamma = 95.5 degrees, Z = 2; diffraction extends
      to at least 2.1 A.

PMID- 10930841
TI  - Characterization, crystallization and preliminary X--ray diffraction analysis of
      acutohaemolysin, a haemolytic toxin from Agkistrodon acutus venom.
AB  - Acutohaemolysin, a phospholipase A(2) (PLA(2)) from the venom of the snake
      Agkistrodon acutus, has been isolated and purified to homogeneity by anion
      exchange chromatography on a DEAE-Sepharose column followed by cation-exchange
      chromatography on a CM-Sepharose column. It is an alkaline protein with an
      isoelectric point of 10.5 and is comprised of a single polypeptide chain of 13
      938 Da. Its N-terminal amino-acid sequence shows very high similarity to Lys49
      type PLA(2) proteins from other snake venoms. Although its PLA(2) enzymatic
      activity is very low, acutohaemolysin has a strong indirect haemolytic activity
      and anticoagulant activity. Acutohaemolysin crystals with a diffraction limit of
      1.60 A were obtained by the hanging-drop vapour-diffusion method. The crystals
      belong to the space group C2, with unit-cell parameters a = 45.30, b = 59.55, c =
      46.13 A, beta = 117.69 degrees. The asymmetric unit contains one molecule.

PMID- 10930842
TI  - Purification, crystallization and preliminary X-ray study of orotidine 5'
      monophosphate decarboxylase.
AB  - Orotidine-5'-monophosphate decarboxylase (ODCase) from Methanobacterium
      thermoautotrophicum has been crystallized with and without the inhibitor 6-azaUMP
      by the vapour-diffusion method. In the absence of the inhibitor, the protein
      crystallizes in space group P4(1)2(1)2 (unit-cell parameters a = b = 56.9, c =
      124.5 A) with one molecule per asymmetric unit; the crystals diffract to 1.8 A
      resolution. In the presence of the inhibitor, the protein crystals are
      monoclinic, space group P2(1) (unit-cell parameters a = 73.0, b = 98.6, c = 73.3
      A, gamma = 104.0 degrees ), with four molecules in the asymmetric unit; the
      crystals diffract to 1.5 A resolution.

PMID- 10930843
TI  - Purification, co-crystallization and preliminary X--ray analysis of the natural
      aspartic proteinase inhibitor IA3 complexed with saccharopepsin from
      Saccharomyces cerevisiae.
AB  - The vacuolar aspartic proteinase from baker's yeast, saccharopepsin, has been co
      crystallized with its natural inhibitor I(A)3, found in the cytosol. The I(A)3
      saccharopepsin complex crystals belong to the space group P6(2)22, with unit-cell
      parameters a = b = 192.1, c = 59. 80 A and one molecule per asymmetric unit. The
      initial X-ray analysis of the complex indicates that the crystals diffract to 5.0
      A, similar to native saccharopepsin crystals. This is probably a consequence in
      part of glycosylation of the native saccharopepsin. Full structural analysis of
      the complex crystal is in progress.

PMID- 10930844
TI  - Crystallization and preliminary X-ray analysis of the thermostable sweet protein
      mabinlin II.
AB  - Mabinlin II is a sweet protein with the highest known thermostablility and is
      isolated from the seeds of Capparis masaikai Levl. grown in south China. Two
      crystal forms of mabinlin II were obtained using the hanging-drop vapour
      diffusion method. One of them diffracts to 2.8 A resolution and belongs to space
      group P2, with unit-cell parameters a = 50.16, b = 50.17, c = 76.60 A, beta =
      99.6 degrees. There are four molecules per asymmetric unit, with a solvent
      content of 35.3%.

PMID- 10930845
TI  - Crystallization and preliminary X-ray crystallographic analysis of Escherichia
      coli CyaY, a structural homologue of human frataxin.
AB  - CyaY is a 106-residue protein from Escherichia coli. It shows amino-acid sequence
      similarity to human frataxin and a frataxin homologue in Saccharomyces
      cerevisiae, Yfh1p. The former is associated with the disease Friedreich ataxia
      and the latter plays a key role in iron homeostasis in mitochondria. CyaY has
      been overexpressed in soluble form in E. coli. The recombinant protein with a
      His(6) tag at its C-terminus has been crystallized at 296 K using polyethylene
      glycol (PEG) 4000 as a precipitant. Native diffraction data have been collected
      to 1.8 A using Cu Kalpha X-rays. The crystals belong to the trigonal space group
      P3(1)21 (or P3(2)21), with unit-cell parameters a = b = 44.66, c = 99.87 A, alpha
      = beta = 90.0, gamma = 120.0 degrees. The asymmetric unit contains one molecule
      of recombinant CyaY, with a corresponding V(m) of 2.13 A(3) Da(-1) and solvent
      content of 42.3%.

PMID- 10930846
TI  - Crystallographic characterization of the membrane-binding domain of radixin.
AB  - Radixin is a protein which cross-links plasma membranes and actin filaments and
      thus forms membrane-associated cytoskeleton. The radixin N-terminal domain, which
      is responsible for membrane association, has been purified and crystallized by
      vapour diffusion with polyethylene glycol 6000. The crystals belong to space
      group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 96.36, c =
      133.16 A, and diffract to a resolution of 3.0 A.

PMID- 10930847
TI  - Crystallization of peptidase T from Salmonella typhimurium.
AB  - Aminotripeptidase (peptidase T) from Salmonella typhimurium and a derivative
      carrying a C-terminal His tag have been crystallized. In both cases, the space
      group was found to be C2, with a single molecule in the asymmetric unit. Crystals
      of the native peptidase T diffract to 2.9 A, but a selenomethionine derivative of
      this protein did not yield good crystals. Crystals of the His-tag peptidase T
      diffracted to 2.6 A, however, and could be used for the production of good
      quality selenomethionine crystals. All 15 methionines, a native metal ion and two
      mercury reactive sites could be located and crystals suitable for MAD data
      collection have been produced.

PMID- 10930848
TI  - beta-carbonic anhydrase from Pisum sativum: crystallization and preliminary X-ray
      analysis.
AB  - Recombinant beta-carbonic anhydrase from the garden pea, Pisum sativum, was
      purified to homogeneity and crystallized. Crystals belong to the orthorhombic
      space group C222, with unit-cell parameters a = 136.3, b = 142.5, c = 201.4 A,
      alpha = beta = gamma = 90 degrees. Crystals typically diffracted anisotropically,
      with a maximal resolution of 2.0 A in the strongest direction. The calculated
      Matthews parameter predicts approximately eight molecules in the asymmetric unit,
      consistent with previous reports of the molecule being an octamer. However,
      examination of the self-rotation function revealed no fourfold symmetry axis and
      multiple weak twofold axes perpendicular to the crystallographic c axis,
      indicating that the oligomerization arrangement is not that of a 422 octamer.

PMID- 10930849
TI  - Crystallization and preliminary X-ray analysis of the EVH1 domain of Vesl-2b.
AB  - Proteins of the Homer/Vesl family are enriched at excitatory synapses and
      selectively bind to a proline-rich consensus sequence in group 1 metabotropic
      glutamate receptors via a domain that shows a strong similarity to the Ena/VASP
      homology 1 (EVH1) domains. EVH1 domains play an important role in actin
      cytoskeleton dynamics. Crystals of the EVH1 domain of murine Vesl-2b were
      obtained that diffract X-rays to 2.4 A resolution. They belong to space group C2,
      with unit-cell parameters a = 112.8, b = 69.9, c = 54.9 A, beta = 110.7 degrees,
      consistent with three molecules per asymmetric unit and a solvent content of 53%.

PMID- 10930850
TI  - Structural role of a detergent molecule in retinoic acid nuclear receptor
      crystals.
AB  - The human nuclear receptor of retinoic acid hRARgamma is a ligand-dependent
      transcription regulator. The presence of a completely ordered dodecyl-alpha-D
      maltoside molecule in the crystal structure of the hRARgamma ligand-binding
      domain (LBD) refined at 1. 3 A resolution is reported. The non-ionic detergent is
      required for stabilization and crystallization of the hRARgamma LBD and mediates
      a crystal contact in the region where coactivator proteins bind. Its dodecyl
      moiety is buried in a hydrophobic channel, whereas the maltoside head group is
      hydrogen bonded to water molecules and polar residue side chains.

PMID- 10930851
TI  - Bulk-solvent correction in direct-methods phasing. erratum
AB  - Equation (12) of the paper by Guo et al. [(2000), Acta Cryst. D56, 451-457] was
      printed incorrectly. The factor (4/3)piR(s)(3) should be omitted. The correct
      equation is as follows f(S) = rho(s)integral(V(P)/N(P)) exp (2piih.r)dV
      approximately Z(s)Phi(2pi|h|R(s)). (12)

PMID- 10930852
TI  - [Society of Dermatology Research: on the way to new advancements].

PMID- 10930853
TI  - [Complaints against dermatologists].

PMID- 10930854
TI  - [Inpatient and outpatient follow-up of grade I malignant melanoma].
AB  - BACKGROUND: In 1995, the French consensus conference on management of patients
      with grade I malignant melanoma recommended clinical examination for patient
      monitoring. To date, only one survey has been conducted to evaluate these
      recommendations and their consequences, providing no means of assessing follow-up
      practices. The aim of this study was to assess follow-up practices in patients
      with grade I malignant melanoma followed in an outpatient private practice
      setting and in a hospital setting with regular appointments. PATIENTS AND
      METHODS: This retrospective study was conducted in collaboration with private
      practice and hospital dermatologists, all members of an association of continuing
      medical education. Medical records of 584 patients with grade I malignant
      melanoma who had undergone surgery between January 1, 1991 and December 31, 1995
      were reviewed. Three hundred twenty-nine patients were followed in an exclusively
      outpatient setting by their private dermatologist and 265 were followed in a
      hospital setting. Follow-up data were: age, sex, date of surgical excision of the
      melanoma, Breslow thickness, date of each follow-up visit, presence of possible
      metastases and mode of diagnosis. RESULTS: Patient features were different in the
      two groups: mainly greater Breslow thickness and more frequent metastatic course
      in patients followed in a hospital setting. Among all patients, 65 (11 p. 100)
      developed metastases. Diagnosis of metastasis was made clinically in 95 p. 100
      whatever the mode of monitoring considered. The number of patients lost to follow
      up was 11p. 100 among those followed in a hospital setting and 42 p. 100 in those
      followed in a private practice setting. Patients lost to follow-up had a higher
      risk of developing metastasis as their average Breslow thickness was 1.7 mm.
      CONCLUSION: This study shows that patients followed in a hospital setting have a
      more severe prognosis than patients followed in private practice. It confirms
      that systematic use of complementary tests is of little interest in detecting
      metastases since over the period considered, the diagnosis of metastasis was made
      clinically in most cases. It also discloses difficulties encountered in
      exclusively outpatient follow-up as a high number of patients were lost to follow
      up in this setting. A systematic appointment fixed by the private dermatologist
      during the follow-up period appears to be needed to ensure good quality follow
      up. Such an appointment system should help reduce the number of patients lost to
      follow-up.

PMID- 10930855
TI  - [Activated protein C resistance and cardiolipin antibodies in leg ulcers].
AB  - BACKGROUND: We conducted a prospective study to determine the prevalence of
      activated protein C resistance and anticardiolipin antibodies in leg ulcers,
      whatever venous, arterial or arteriovenous. PATIENTS AND METHODS: One hundred
      fifteen patients hospitalized for leg ulcers, without antiphospholipid syndrome
      were included. The vascular abnormalities were studied by clinical examination,
      Doppler, duplex Doppler and, when required, arteriography. Activated protein C
      resistance was isolated by a "classic" test (normalized APTT ratio in PCa
      presence or absence) and by a "second generation test" (by preliminary dilution
      with deficient factor V plasma). All patients with abnormal results on the second
      test were screened for the factor V Leiden (by PCR amplication with use of
      restriction enzymes). Anticardiolipin antibodies were investigated with an ELISA
      method with Harris standards as reference, in which the positive threshold was
      established at 20 units. RESULTS: Among these 115 patients, 50 venous (43.5 p.
      100), 23 arterial (20 p. 100), 42 arteriovenous (36.5 p. 100) leg ulcers were
      identified. Activated protein C resistance was isolated in 12 cases (10.4 p. 100)
      (heterozygous carriers): 7 venous ulcers, 3 arteriovenous, 2 arterial.
      Anticardiolipin antibodies were measured at significant level in 49 cases (42.6
      p. 100): 21 venous ulcers, 18 arteriovenous, 10 arterial. DISCUSSION: In this
      study, there was no statistical difference between the activated protein C
      resistance prevalence in leg ulcers when compared with Lorraine population
      (p=0.27). Factor V Leiden or anticardiolipin antibodies abnormalities were
      isolated in 56 cases (48.7 p. 100) without statistical difference between the 3
      types of ulcers. Finally, the pathophysiology of venous, arterial and
      arteriovenous leg ulcers remains complex, suggesting several coagulation
      perturbations.

PMID- 10930856
TI  - [Comparative study of efficacy and effect on plasma cortisol levels of micronised
      desonide cream 0.1 p. 100 versus betamethasone dipropionate cream 0.05 p. 100 In
      the treatment of childhood atopic dermatitis].
AB  - OBJECTIVE: Systemic side effects of local corticosteroid therapy may occur when
      treating chronic inflammatory dermatoses in children. We compared the effect of
      micronized desonide cream 0.1 p.100 versus betamethasone dipropionate cream 0.5
      p.100. PATIENTS AND METHODS: A randomized double-blind trial was conducted to
      assess the efficacy of micronized desonide cream 0.1 p.100 (group 1) versus
      bethamethasone cream dipropionate 0.05 p.100 (group 2) in children treated for
      atopic dermatitis and to compare their effects on serum cortisol levels 8 hours
      after administration. Twenty-nine patients, mean age 13.8 months were included
      (15 in group 1 and 14 in group 2). The creams were applied twice a day from day 1
      to 5 then once a day from day 6 to 7 and finally once every two days to day 15.
      RESULTS: The two treatments were effective with a decrease in body surface area
      involved and an improvement in lesion score from day 5 to day 20. Cortisolemia
      fell off significantly for both treatments between day 0 and day 5 (group 1:
      Deltad5=-4.74 mg/ml, p=0.01; group 2: Deltad5=-13.06 mg/ml, p<0.0001), only for
      group 2 between day 0 and day 20 (Deltad20=-7.38 mg/ml, p=0.02) and to a lesser
      degree between day 0 and day 30 (Deltad30=-3.18 mg/ml, p=0.06). The decrease was
      greater in group 2 than in group 1 on day 5 (p=0.01) and to a lesser degree at
      day 20 (p=0.06). CONCLUSIONS: Micronized desonide cream 0.1 p.100 has less
      potential for suppressing the adrenal cortisol axis than betamethasone
      dipropionate cream 0.05 p.100 while the therapeutic effect on childhood atopic
      dermatitis is the same.

PMID- 10930857
TI  - [Herpes labialis and genitalis in general medicine].
AB  - OBJECTIVE: The purpose of this study was to determine the respective importance
      of herpes labialis and genitalis in patients consulting general practitioners and
      ascertain their knowledge and opinions concerning herpes labialis and genitalis
      in order to analyze patient behavior in case of flare-ups. PATIENTS AND METHOD: A
      questionnaire was proposed to a representative sample of patients aged 15 years
      and older seen at consultation by 49 general practitioners participating in the
      General Medicine Observatory of the French Society of General Practitioners.
      RESULTS: Among the 4,403 patients who responded, a known history of herpes
      labialis was reported by 39. 9 p.100 and of herpes genitalis by 2.5 p.100. Their
      answers to the questions demonstrated insufficient knowledge of avoidable risks
      of herpes as a sexually transmitted disease, with very significant
      misunderstanding by men. Among the 1,711 patients who had experienced herpes
      labialis, 62.9 p.100 initiated self-medication, 29 p.100 preferred to wait and
      see and 7.5 p.100 sought medical assistance. Among the 108 patients who had
      experienced herpes genitalis, at the last flare-up 40 p.100 initiated self
      medication, 7.5 p.100 preferred to wait and see and 52 p.100 sought medical
      assistance. The general practitioner was the first physician consulted for both
      types of herpes. DISCUSSION: This study illustrates the importance of herpes
      infections in the general medicine patients. It also confirms that new
      interventional strategies are needed both for health care and for health
      education.

PMID- 10930858
TI  - [Thalidomide].

PMID- 10930859
TI  - [Mammary staphylococcal cellulitis of the newborn].
AB  - BACKGROUND: Neonatal cellulitis is usually caused by staphylococcal infection of
      the mammary gland which has generally reached the stage of abscess formation at
      the time of diagnosis. The circumstances of onset and possible complications
      remain poorly known. We report a recent case. CASE REPORT: A female neonate
      developed major bilateral mammary hypertrophy. Her mother had tried to express
      the breasts, fearing "congestion". Three days later, the right breast showed
      signs of inflammation with a fluctuant central zone suggestive of a cellulitic
      infectious abscess confirmed at ultrasound. Recovery was achieved with incision
      and antistaphylococci antibiotic therapy. DISCUSSION: Mammary cellulitis of the
      newborn appears to generally occur following an attempt to manipulate a pre
      existing physiological hypertrophy of the breast. Staphylococcus aureus is the
      most commonly found agent. Early surgical care is generally required as there is
      a real risk of progression to necrotizing faciitis.

PMID- 10930860
TI  - [Gleich's syndrome].
AB  - BACKGROUND: Episodic angioedema with eosinophilia is a new syndrome associating
      hypereosinophilia, episodic angioedema and elevation of immunoglobulin M. This
      syndrome, first described by Gerald Gleich, has a good prognosis and no organ
      involvement. CASE REPORT: A 39-year old woman developed for 10 years, recurrent
      episodes of swelling, weight gain of 4 to 6 kg, hypereosinophilia and
      hyperimmunoglobulinemia M and G. All symptoms disappeared spontaneously within a
      few days. Numerous investigations (cutaneous, cardiac, pulmonary, immunologic,
      parasitologic) were negative. The patient was recently hospitalized because of
      increased recurrence of episodes and major discomfort. We noted hypereosinophilia
      up to 30. 731 eosinophils/mm(3), elevated lactate dehydrogenase to 902 U/l (N:
      204-412), elevated eosinophile cationic protein to 371 microg/l (N<12) and
      elevated immunoglobulin E to 140 U/l (N<100). Renal, pulmonary and cardiac
      functions were normal. Bone marrow biopsy showed no abnormality. DISCUSSION:
      Gleich's syndrome is a benign but often incapacitating disease of unknown
      etiology. Systemic glucocorticoids may control flare-ups.

PMID- 10930861
TI  - [Radiodermatitis after transjugular intrahepatic portosystemic shunt: 4 cases].
AB  - BACKGROUND: Radiodermatitis following invasive radiographic procedures has been
      reported recently in the literature, mainly after cardiac catheterization. Only
      two publications are related to transjugular intrahepatic portosystemic shunt
      (TIPS), a recently introduced angiographic technique for achieving portal
      decompression. CASE REPORTS: We report four cases of radiodermatitis following a
      transjugular intrahepatic portosystemic shunt. A 63-year-old woman developed in
      1997 a chronic radiodermatitis under the right scapula; a shunt was placed in
      1992; from 1992 to 1997, she had a second transjugular intrahepatic portosystemic
      shunt and thereafter four dilatations. A 50-year-old man developed in 1994 a
      radio-induced ulceration in the same area, one week after a transjugular
      intrahepatic portosystemic shunt; the same year the shunt was expanded. The
      patient had a second transjugular intrahepatic portosystemic shunt in 1995; at
      that time, the cutaneous lesions evolved into chronic radiodermatitis. In 1995 a
      67-year-old man developed chronic radiodermatitis under the right scapula; a
      transjugular intrahepatic portosystemic shunt was placed in 1992; endoprosthesis
      was dilated four times from 1992 to 1995. A 82-year-old women developed in 1993
      an ulcerated radiodermatitis, five days after a transjugular intrahepatic
      portosystemic shunt. DISCUSSION: The major advantage of the transjugular
      intrahepatic portosystemic shunt is the ability to provide portosystemic
      decompression without major surgery. However, radiation exposure during the
      procedure is sometimes very high. Otherwise the prosthesis is readily blocked up;
      this side-effect requires repeated angiographic dilatations. The procedures were
      very long by all our patients. This explains the high absorbed radiation doses.
      Transjugular intrahepatic portosystemic shunt and cardiac catheterization are not
      the only procedures at risk. A lot of invasive radiographic techniques can result
      in high radiation exposure and hence radiodermatitis.

PMID- 10930862
TI  - [Solitary congenital histiocytoma: two cases].
AB  - BACKGROUND: Solitary histiocytoma is an uncommon form of Hashimoto-Pritzker
      syndrome and an exceptional type of histiocytosis with cells of undetermined
      origin. A solitary often ulcerated congenital nodule is generally observed. We
      report two cases, one of each form. CASE REPORTS: Both cases presented an
      ulcerative budding congenital tumefaction of the plantar aspect of the right foot
      for the first child and the parieto-axillary region in the second. Histology
      disclosed a granulomatous infiltrate of histiocytes positive for specific
      immunolabels (protein S100 and CD1a). In the first case, electron microscopy
      revealed histiocytes devoid of Birbeck granules and myelinoid bodies leading to
      the diagnosis of Langerhans histiocytosis with cells of unknown origin. In the
      second case, 18 p. 100 of the cells contained Birbeck granules. There has been no
      recurrence after a 5-year follow-up in a case. DISCUSSION: These cases recall the
      congenital nature of some types of solitary histiocytomas. Indeed, congenital
      Langerhans histiocytoma can occur as a unique nodule. The tumefaction may lie in
      any localization. Histological diagnosis is required. The benign nature of these
      lesions is confirmed by the absence of distant lesions and the lack of recurrence
      after complete excision. About a dozen cases have been reported. Most have been
      Hashimoto-Pritzker syndromes. Only one case has been reported with cells of
      undetermined origin. The diagnosis of histiocytosis with cells of undetermined
      origin is made when the ultrastructure study demonstrates the vacuity of the
      histiocyte cytoplasm. This condition is similar to Hashimoto-Pritzker syndrome by
      the absence of recurrence and systemic diffusion. It can however be observed in
      adults. The undetermined cell types would correspond different phases of
      Langerhans cell maturation or involution.

PMID- 10930863
TI  - [Infiltrative extensive lesions. Tertiary mucocutaneous syphilis].

PMID- 10930864
TI  - [Purplish nodules on the lymphedema. Stewart-Treves syndrome].

PMID- 10930865
TI  - [HHV-8/KSHV. II--Associated diseases].

PMID- 10930866
TI  - [Botulinum toxin in dermatology].

PMID- 10930867
TI  - [Matrix metalloproteases and skin].

PMID- 10930868
TI  - [Gingival hypertrophy and tacrolimus].

PMID- 10930869
TI  - [Vidal pro].

PMID- 10930870
TI  - [Is systematic excision of pigmented spots on the plantar aspect of the foot
      warranted?].

PMID- 10930871
TI  - [Low-power laser and recurrent labial herpes].

PMID- 10930872
TI  - [History of eczema and atopic dermatitis].

PMID- 10930874
TI  - [Calendar] [In Process Citation]

PMID- 10930875
TI  - [It's a fact. Just ask them: regarding the motor system, clinicians do not like
      very much ultrasonography].

PMID- 10930873
TI  - [Rothmund-Thomson syndrome and defective DNA excision-resynthesis repair].

PMID- 10930876
TI  - [Ultrasonography of muscles and tendons].
AB  - Technical progress, namely in the field of US probes, allow a more accurate study
      of muscles and tendons. The US appearance of muscles and tendons is closely
      related to their fibrous structure. Knowledge of the anatomy of fibrous
      structures helps understand normal and abnormal images. A wide range of lesions,
      of muscles and tendons, including trauma (luxation and rupture), infection,
      tumors as well as degeneration (tendinitis) is presented.

PMID- 10930877
TI  - [Osteo-articular ultrasonography of the shoulder].
AB  - The objective of this course is to present the normal and pathological aspects of
      the various periarticular structures of the shoulder, and the practical
      modalities of their analysis. The anatomy and pitfalls of tendon imaging is
      recalled, as well as the interest to detect intra and peri articular effusions.
      The semiological aspects of complete and partial tears of the rotator cuff and
      the various impingement syndromes, well demonstrated with dynamic sonography, are
      then studied. The examination requires time and knowledge but the diagnostic and
      therapeutic impact is very important regarding the low cost of this technique.
      The standardisation of the procedure and the production of normal reference
      images seems to guarantee a global increase in quality of the sonographic
      examinations.

PMID- 10930878
TI  - [Ultrasonography of the wrist and the hand].
AB  - There are six large groups of indications for sonographic study of the wrist and
      the hand: study of nerves, tendons, synovial cysts, ligaments and bony
      structures, diagnosis of Stener lesion, and search of pulley's abnormalities at
      the fingers. Use of high frequency probes as well as a gel-pad are required. The
      examination is essentially delicate, comparative and dynamic. Some structures
      such as small soft collections may disappear when the pressure of the probe is
      too heavy. An abnormality may become obvious only by comparison with the normal
      side, or appear only in a special position, such like synovial cysts. Recognition
      of osseous landmarks is essential, especially in the study of the wrist.

PMID- 10930879
TI  - [Osteo-articular ultrasonography of the hip and the knee].
AB  - Experience in the field of musculoskeletal diseases and advanced technology of
      medical sonographers allow increasing accuracy in US investigations of most
      lesions of both hip and knee superficial tendons. In this field, US is more and
      more widely replacing other imaging modalities, including MR imaging.
      Ultrasonography may now be used also for articular diseases purpose, including
      joint effusion, synovitis, intraarticular loose bodies, ligamentous injuries,
      articular cysts, as well as for certain osseous lesions like stress or
      insufficiency fractures of superficial bones. However, ultrasonography has still
      to be evaluated for these latter indications.

PMID- 10930880
TI  - [Ultrasonography of tendons and ligaments of foot and ankle].
AB  - The main ligaments and tendons of the ankle and the hind-foot can now be studied
      by US. This simple and safe technic constitutes a more and more reliable
      alternative to MRI and CT scan. AIMS: Know the normal US appearance of the
      tendons and ligaments of the ankle and the hind-foot, and how to study them with
      US. Know their main usual pathological appearance.

PMID- 10930881
TI  - [Imaging of synovial lesions, neoplastic or non-neoplastic].
AB  - The purpose of this paper is to present the contribution of imaging in the
      assessment of synovial diseases, especially in the differentiation between
      infectious synovitis and rheumatoid arthritis, and in the diagnosis of tumoral
      and pseudotumoral synovial lesions (idiopathic (osteo)chondromatosis, pigmented
      villonodular synovitis, synovial hemangioma, lipoma arborescens...).

PMID- 10930882
TI  - [Imaging of chronic hip pain in adults].
AB  - Adult hip pathologies are mainly represented by the degenerative disease, so
      called "osteoarthrosis, or more precisely coxarthrosis". The means of imaging are
      exposed, according to their specific value: X Rays (measurement of the
      characteristic angles of the adult hip), Arthrography, CT Scanner, Arthro-CT
      Scanner, MRI, Bone Scintigraphy, Ultrasonography. Clinical findings differentiate
      a mechanical syndrome and an inflammatory syndrome. The coxarthrosis is the most
      frequent, under two forms: primary (idiopathic) coxarthrosis and secondary
      coxarthrosis. Primary (idiopathic) coxarthrosis has a localised narrowing of the
      joint space, osteophyte formation, subchondral sclerosis, cyst formation. The
      destruction progresses slowly, in 10 to 15 years leading to a complete
      destruction. Bilaterality is frequent. it is treated with total hip prosthesis.
      There is a rapid form (1 to 2 years) (Postel's Disease). Secondary coxarthrosis
      occurs after architectural vice, chondral diseases, lack of balance between the
      size of the head and the acetabulum as in the case of previous fracture or
      dislocation, avascular bone necrosis of the head of the femur, Paget's disease.
      Calcium pyrophosphate Deposition disease (CPPD) involves mostly aged women, and
      also leads to cox-arthrosis. Avascular bone necrosis of the head of the femur
      involves young adults. Bilateral involvement are frequent. MRI is the most
      sensitive and the most specific means of early diagnosis, The area of bone
      necrosis appears as well defined modifications of the upper head of the femur,
      precisely surrounded by a low signal intensity line on both Ti and T2 weighted
      imaging. MRI shows articular effusion, bone marrow edema. Scintigraphy gives
      early findings which are a characteristic, but non specific, hot spot. CT scanner
      is used for hip destruction evaluation. o Algodystrophy: transient osteoporosis
      of the hip has a cyclic course, lasting 3 to 9 months. MRI shows an inflammatory
      pattern in the area of the process(dark in Ti and white in T2, with positive
      Gadolinium response). Scintigraphy is positive. Staphylococcus location in the
      hip can be acute or chronic. MRI shows joint effusion, cystic formation and
      subchondral non specific modifications. Tuberculosis of the hip joint is
      relatively rare. Greater trochanteric tuberculous involvement is possible under
      special contexts. Chronic Inflammatory diseases are represented by Rheumatoid
      Arthritis, Spondylarthritis and other chronic inflammatory diseases. Synovial
      tumors such as Pigmented Villo Nodular Synovitis, Primary Osteochondromatosis,
      synovial sarcoma have special presentations. The subchondral bone can be involved
      by amorphous depositions such as in tophaceous gout, different varieties of
      lipidosis, amyloidosis, reticulo histiocytosis. Pen arthropathies are
      enthesopathies in the anterior rectus tendon, calcifying tendonitis (not to be
      confused with calcifying soft tissue tumor/chondrosarcoma). The pelvis bone and
      the femur are involved by primary and secondary tumors or by insufficiency
      fractures which can mislead to hip pathologies.

PMID- 10930883
TI  - [This new notebook of continuing education is dedicated to neuroradiology].

PMID- 10930885
TI  - [Neurovascular cross-compression syndromes of the cerebellopontine angle].
AB  - Neurovascular cross-compression syndromes involve the Vth, VIIth, VIIIth, and
      IXth cranial nerves. They share in common the same physiopathologic mechanism and
      are demonstrated by T2 volumetric MR explorations (CISS 3D and 3D TSE sequences)
      and 3D TOF MRA sequences of the posterior circulation. The cross compression is
      located at the root entry zone. Arterial loops are the classical offenders while
      venous compressions are less frequently encountered.

PMID- 10930884
TI  - [Cerebellopontine angle tumors in adults].
AB  - Cerebellopontine angle tumors in adults are mainly benign and extra-axial.
      Magnetic resonance imaging is the first method for their diagnosis, CT being more
      useful for bony structures evaluation. Vestibular schwannoma is the most common
      lesion, it presents as a rounded mass centered along the axis of the internal
      acoustic meatus, the largest portion being in the cerebellopontine angle. The
      tumor enhances after Gadolinium administration. Meningioma is the second most
      common tumor; this slow growing mass has a wide attachment to the adjacent dural
      mater and is dramatically enhanced by contrast. Epidermoid cyst the third mass,
      is an extra-axial lesion with the signal is similar to the one of cerebrospinal
      fluid. Other lesions such as lipoma, papilloma, glioma or metastasis account for
      less than 1% of the cerebellopontine angle cistern tumors in adults.

PMID- 10930886
TI  - [Radioanatomy of the cerebral cortex. Practical guide of identification].
AB  - Cerebral sulci identification process is based on several formal rules: it
      consists a series of steps allowing the identification of the major sulci. The
      process may be variable for each of us and we propose to read the images in
      certain order starting with the frontal lobe and its superior frontal gyrus than
      precentral and central gyri followed by the lateral fissure. Then the insular,
      lateral parietal and medial hemispheric regions. Finally the major sulci within
      the temporal and occipital lobes are described in the frontal plane. This
      presentation indicates the principal rules of cerebral lobes'identification, the
      basis of variability perception and the localization of small lesions allowing an
      accurate correlation with clinical findings and a suitable therapeutic procedure.

PMID- 10930887
TI  - [Brain functional MRI: physiological, technical, and methodological bases, and
      clinical applications].
AB  - Brain functional MRI (fMRI) provides an indirect mapping of cerebral activity,
      based on the detection of the local blood flow and oxygenation changes following
      neuronal activity (BOLD contrast, Blood Oxygenation Level Dependent). fMRI allows
      us to study non invasively the normal and pathological aspects of cortical
      functional organization. Each fMRI study compares two different states of
      activity. Echo-Planar Imaging (EPI) is the technic of choice that makes it
      possible to study the whole brain at a rapid pace. Activation maps are calculated
      from a statistical analysis of the local signal changes. Functional MRI is now
      becoming an essential tool in the neurofunctional work-up of many neurosurgery
      patients, as well as the reference method to image normal or pathologic
      functional brain organization in adults and children.

PMID- 10930888
TI  - [Lumbar lateral recess and intervertebral foramen. Radio-anatomical study].
AB  - The recent developments in Computed Tomography (CT) and Magnetic Resonance
      Imaging (MRI) allow an accurate analysis of the anatomical structures of the
      lateral recess and of the neural foramen (vertebral body, pedicle, zygapophyseal
      joints, ligamentum flavum, intervertebral disk) and their contents (spinal
      ganglion, nerves roots, foraminal veins, surrounding fat). The aim of this study
      is 1) to describe the normal anatomy and variants of the lateral recess and of
      the lumbar neural foramen, and 2) to present the main diseases involving this
      anatomical area.

PMID- 10930889
TI  - [The lumbar epidural space. Radio-anatomical study].
AB  - The epidural space which extends along the spine, surrounds the dural sac and is
      bounded by the bony and ligamentous structures of the vertebral canal. The
      knowledge of the anatomy of this region is important because the high frequency
      of the pathological processes in this area (tumoral, infections, vascular). The
      purpose of this presentation is to present the normal radio-anatomy of the lumbar
      epidural space and then the main pathological processes of this region.

PMID- 10930890
TI  - Review article: comparison of the pharmacokinetics, acid suppression and efficacy
      of proton pump inhibitors.
AB  - Proton pump inhibitors have dramatically influenced the management of acid-peptic
      disorders in recent years. They all have a broadly similar mechanism of action
      and are extensively metabolized in the liver via cytochromes P450 2C19 and 3A4.
      There is some variation in their potential for drug interactions due to
      differences in enzyme inhibition. Relatively few serious adverse effects have
      been reported for the proton pump inhibitors. Comparative studies of acid
      suppression suggest that lansoprazole and pantoprazole have a potency similar to
      that of omeprazole on a mg for mg basis; however, rabeprazole may have a greater
      potency than omeprazole. Lansoprazole and rabeprazole display a more rapid onset
      of maximal acid suppression than the other proton pump inhibitors. Comparative
      studies using proton pump inhibitors for the treatment of reflux oesophagitis,
      duodenal ulcer healing and Helicobacter pylori eradication show little overall
      difference in outcome between the proton pump inhibitors when used in their
      standard doses. Lansoprazole and rabeprazole provide earlier and better symptom
      relief than the other proton pump inhibitors in some studies of peptic ulcer
      treatment. The few studies of gastric ulcer treatment suggest that there is an
      advantage in using the proton pump inhibitors that have a higher standard daily
      dose.

PMID- 10930891
TI  - Review article: the clinical influence of Helicobacter pylori in effective acid
      suppression-implications for the treatment of gastro-oesophageal reflux disease.
AB  - The relationship between gastro-oesophageal reflux disease (GERD) and
      Helicobacter pylori is unclear. Recent data indicate that H. pylori probably
      exerts a protective effect against GERD. In recent years, the interaction between
      H. pylori, proton pump inhibitors and GERD has been widely studied. Currently
      available proton pump inhibitors produce significantly higher intragastric pH in
      H. pylori-positive patients than in those who are H. pylori negative, and this
      phenomenon may be clinically relevant. The mechanisms responsible for this
      difference in efficacy are not fully understood, although there are two major
      theories. Ammonia, produced by H. pylori, is able to neutralize gastric acid, and
      thus apparently increase the effect of acid suppressive agents (the 'ammonia
      theory'). The other theory is that decrease in acid output is due to the
      development of corpus gastritis during treatment with a proton pump inhibitor
      (the 'gastritis theory'). Treatment strategies to overcome this lowered
      sensitivity to acid suppression are to increase the frequency/dose of a proton
      pump inhibitor or to add an H2-receptor antagonist in the evening-but both have
      pharmaco-economic implications. An agent that could provide adequate pH control
      regardless of H. pylori status would be highly beneficial in the treatment of
      GERD, and may also lower treatment costs.

PMID- 10930892
TI  - Review article: treatment of Helicobacter pylori infection with ranitidine
      bismuth citrate- or proton pump inhibitor-based triple therapies.
AB  - Triple therapy, combining a proton pump inhibitor with clarithromycin (C) and
      either amoxycillin (A) or a nitro-imidazole (I) is the standard in Helicobacter
      pylori eradication therapy. Recently, triple therapies based on ranitidine
      bismuth citrate (RBC) have emerged as an alternative. This review examines the
      current literature for studies directly comparing proton pump inhibitor- with RBC
      based triple therapies. Seventeen studies were identified, of which three have
      been published as a full paper. Eradication rates in an intention-to-treat
      analysis ranged from 51 to 98%. No large difference in cure rates between the
      different regimens was demonstrated, although the RBC-I-C combination was
      somewhat superior. No definite conclusions could be made about the impact of
      metronidazole or clarithromycin resistance since only three studies performed a
      formal resistance analysis. No serious side-effects were reported, and dropout
      rates were equal for the two regimens. Both RBC- and proton pump inhibitor-based
      triple therapies are highly effective. If one prefers a imidazole/clarithromycin
      combination the evidence presented here suggests that RBC should be used instead
      of a proton pump inhibitor. Larger studies comparing both forms of triple
      therapy, using proper resistance analysis, are needed before final conclusions
      can be reached regarding efficacy in the setting of bacterial resistance.

PMID- 10930893
TI  - Non-absorbable antibiotics for managing intestinal gas production and gas-related
      symptoms.
AB  - BACKGROUND: Simethicone, activated charcoal and antimicrobial drugs have been
      used to treat gas-related symptoms with conflicting results. AIM: To study the
      relationship between gaseous symptoms and colonic gas production and to test the
      efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these
      symptoms. METHODS: Intestinal gas production was measured by hydrogen (H2) and
      methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34
      functional patients. Only the 34 functional patients took part in a double-blind,
      double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7
      days), or activated charcoal (400 mg b.d per 7 days). The following parameters
      were evaluated at the start of the study and 1 and 10 days after therapy:
      bloating, abdominal pain, number of flatus episodes, abdominal girth, and
      cumulative breath H2 excretion. RESULTS: Hydrogen excretion was greater in
      functional patients than in healthy volunteers. Rifaximin, but not activated
      charcoal, led to a significant reduction in H2 excretion and overall severity of
      symptoms. In particular, in patients treated with rifaximin, a significant
      reduction in the mean number of flatus episodes and of mean abdominal girth was
      evident. CONCLUSIONS: In patients with gas-related symptoms the colonic
      production of H2 is increased. Rifaximin significantly reduces this production
      and the excessive number of flatus episodes.

PMID- 10930894
TI  - Enhanced bioavailability of azathioprine compared to 6-mercaptopurine therapy in
      inflammatory bowel disease: correlation with treatment efficacy.
AB  - BACKGROUND: Azathioprine and 6-mercaptopurine have proven efficacy in the
      treatment of Crohn's disease. Immunosuppression is mediated by their
      intracellular metabolism into active 6-thioguanine metabolites, and clinical
      responsiveness to therapy in patients with inflammatory bowel disease has been
      correlated with the measure of erythrocyte 6-thioguanine levels. AIMS AND
      METHODS: To perform a dosing equivalency analysis and comparison of clinical
      efficacy in 82 patients with inflammatory bowel disease on long-term (> 2 months)
      therapy with either branded azathioprine (Imuran) (n=26), generic azathioprine
      (n=38), or 6-mercaptopurine (n=18), based on the measurement of erythrocyte 6
      thioguanine metabolite levels. RESULTS: Disease remission was achieved in 51% (42
      out of 82) of patients treated with either azathioprine or 6-mercaptopurine
      therapy, and correlated well with high erythrocyte 6-thioguanine levels (> 250
      pmoles/8 x 108 RBCs). Patients treated with either branded azathioprine or 6
      mercaptopurine achieved significantly higher erythrocyte 6-thioguanine levels
      than patients treated with generic azathioprine, thereby suggesting that branded
      azathioprine has improved oral bioavailability compared to generic azathioprine.
      These data are consistent with the putative immunosuppressive role of 6
      thioguanine metabolites in the treatment of inflammatory bowel disease, and
      provides a basis for developing a therapeutic index of clinical efficacy based on
      the measurement of erythrocyte 6-thioguanine metabolite levels. CONCLUSIONS: Our
      results suggest that differences in bioavailability may have clinical relevance
      when considering the need to optimize erythrocyte 6-thioguanine metabolite levels
      in patients deemed unresponsive to treatment on conventional drug dosages.

PMID- 10930895
TI  - Randomized comparison of unfractionated heparin with corticosteroids in severe
      active inflammatory bowel disease.
AB  - BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory
      bowel disease. AIM: A randomized pilot study, to compare unfractionated heparin
      as a first-line therapy with corticosteroids in colonic inflammatory bowel
      disease. METHODS: Twenty patients with severe inflammatory bowel disease
      (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either
      intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks
      (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral
      prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5
      days, non-responders in each treatment group were commenced on combination
      therapy. Response to therapy was monitored by: clinical disease activity
      (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and
      Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid
      glycoprotein, endoscopic and histopathological grading. RESULTS: The response
      rates were similar in both treatment groups: clinical activity index (heparin vs.
      steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic
      (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both
      treatments were well-tolerated with no serious adverse events. CONCLUSION:
      Heparin as a first line therapy is as effective as corticosteroids in the
      treatment of colonic inflammatory bowel disease. Large multicentre randomized
      comparative studies are required to determine the role of heparin in the
      management of inflammatory bowel disease.

PMID- 10930896
TI  - Chemotactic properties of ICAM-1 and PECAM-1 on neutrophil granulocytes in
      ulcerative colitis: effects of prednisolone and mesalazine.
AB  - BACKGROUND: ICAM-1 seems to exhibit effects other than passive
      leucocyte/endothelial interaction. AIM: To investigate the attracting properties
      of selected adhesion molecules, assessing the influence of the two major anti
      inflammatory drugs in ulcerative colitis, prednisolone and mesalazine. METHODS:
      Circulating neutrophils (11 ulcerative colitis, 15 controls) were assessed in
      microchemotaxis chambers by the leading front technique, using physiologically
      relevant concentrations of ICAM-1 (0.005-5000 pM), PECAM-1 (0.001-1000 nM), and P
      selectin (0.01-100 nM). Neutrophils pre-incubated with prednisolone (10(-8)-10(
      4) M) or mesalazine (0.65-10. 4 nM) were assessed towards ICAM-1. RESULTS:
      Migration of neutrophils towards ICAM-1 showed a bell-shaped curve with a maximum
      at 5 pM (migration: 37.7 microm; P<0.001), whereas PECAM-1 attracted neutrophils
      equally in the range of 0.1-10 nM (25.0 microm; P<0.001). P-selectin had no cell
      attracting effect. No differences were detected between cells from ulcerative
      colitis patients and controls. Pre-treatment with prednisolone decreased the cell
      attracting effect of ICAM-1 in a dose-dependent manner to 72% of the basal
      migration (P<0.001). Conversely, prednisolone showed a pro-chemokinetic effect by
      increasing the spontaneous locomotion of neutrophils by 40% (P<0.001).
      CONCLUSIONS: Specific chemotactic properties were observed for ICAM-1 and PECAM
      1. Prednisolone exhibited a dual effect in inhibiting the ICAM-1-mediated
      migration and stimulating the general locomotion of neutrophils.

PMID- 10930897
TI  - Topical and intravenous administration of trefoil factors protect the gastric
      mucosa from ethanol-induced injury in the rat.
AB  - BACKGROUND: hTFF2 and pTFF2 (formerly PSP and hSP, respectively) are members of
      the trefoil factor family (TFF) and are distributed throughout the
      gastrointestinal tract in both normal and diseased tissue. Trefoil factors have
      been shown to exert a mucosal protectant and/or healing role in a number of
      animal models but controversy exists surrounding this property in relation to
      their dose and route of administration. AIM: To investigate the effects of
      topically applied and intravenously infused trefoil factors (hTFF2 and pTFF2) and
      prostaglandin E2 on ethanol-induced gastric mucosal damage in rats. METHOD: A
      gastric chamber preparation in the anaesthetized rat was used. Injury was caused
      by exposing the gastric mucosa to absolute ethanol for 1 min. Trefoil factors or
      prostaglandin E2 were administered either intravenously or topically before and
      after the introduction of absolute ethanol onto the gastric mucosa. Damage was
      assessed by measurement of gastric mucosal Na+ leakage and area of macroscopic
      injury. RESULTS: Like prostaglandin E2, intravenous administration of hTFF2 and
      pTFF2 reduced both the gastric mucosal Na+ leakage and the mean area of damage
      caused by ethanol. Similarly, treatment of the gastric mucosa with topical
      application of hTFF2 at doses of 120 microg/kg and above reduced the Na+ leakage
      and the area of damage. pTFF2 at 120 microg/kg and 1.2 mg/kg applied topically
      produced a marked reduction in total area of damage. CONCLUSION: Intravenously
      infused hTFF2 and pTFF2 protect the gastric mucosa from ethanol-induced damage in
      the anaesthetized rat. In addition, topical application of trefoil factors also
      was effective at protecting the gastric mucosa from injury at doses lower than
      previously reported.

PMID- 10930898
TI  - Cisapride provides symptomatic relief in functional dyspepsia associated with
      gastric myoelectrical abnormality.
AB  - OBJECTIVE: We evaluated the effects of cisapride (10 mg t.d.s. and 20 mg b.d.) on
      gastrointestinal symptoms and gastric myoelectrical activity in patients with
      functional dyspepsia. Myoelectrical activity was measured by electrogastrography.
      METHODS: Patients with functional dyspepsia, defined as discomfort in the
      epigastrium, a negative endoscopy, and clinical symptoms of dyspepsia, were
      enrolled. A total of 38 patients participated in the study (23 female; 15 male;
      24-72 years of age). Screening electrogastrography identified those with a normal
      electrogastrogram (14 subjects) and those with an abnormal electrogastrogram (24
      patients). Patients were randomly assigned to 2 weeks of placebo or 2 weeks of
      cisapride (10 mg t.d.s.); both groups then received 2 weeks of cisapride (20 mg
      b.d.). Electrogastrograms were repeated at the end of each 2-week treatment
      period. RESULTS: Cisapride 10 mg t.d.s. significantly improved symptoms in all
      patients. An additional 2 weeks of treatment with cisapride 20 mg b.d. led to
      continued improvement in symptoms in all patients, with significant improvement
      in the group with abnormal baseline electrogastrograms. Cisapride significantly
      improved postprandial bloating and discomfort in patients with abnormal baseline
      electrogastrograms. Cisapride also significantly improved postprandial gastric
      myoelectrical activity as measured by electrogastrography in patients with
      abnormal baseline electrogastrograms. CONCLUSION: Cisapride provides symptomatic
      relief and improves gastric myoelectrical abnormalities in patients with
      functional dyspepsia.

PMID- 10930899
TI  - Helicobacter pylori infection influences nocturnal gastric acid breakthrough.
AB  - BACKGROUND: Nocturnal gastric acid breakthrough is defined as night-time periods
      when gastrin pH falls below 4.0 for greater than 1h during administration of a
      proton pump inhibitor. This phenomenon is a serious problem for patients who
      require strict control of their gastric acid secretions. AIM: To investigate the
      prevalence of nocturnal gastric acid breakthrough in Japanese subjects during
      administration of rabeprazole, and to clarify the relationship between
      Helicobacter pylori infection and nocturnal gastric acid breakthrough. METHODS:
      Thirty-one normal male volunteers were examined by ambulatory 24 h gastric pH
      monitoring four times: without medication, after a morning or an evening dose of
      20 mg rabeprazole, and after administration of an H2-receptor antagonist at
      bedtime, in addition to the morning dose of rabeprazole. H. pylori infection was
      determined by the 13C-urea breath test and an assay for serum anti-H. pylori
      antibody. RESULT: Nocturnal gastric acid breakthrough was observed in 12 patients
      (39%) after the morning dose of 20 mg rabeprazole. In all cases, nocturnal
      gastric acid breakthrough was inhibited completely by administration of the H2
      receptor antagonist at bedtime. Only one patient with nocturnal gastric acid
      breakthrough had H. pylori infection. CONCLUSION: The absence of H. pylori
      infection appears to be closely related to the occurrence of nocturnal gastric
      acid breakthrough during dosing with a proton pump inhibitor.

PMID- 10930900
TI  - Pharmacodynamics and kinetics of omeprazole MUPS 20 mg and pantoprazole 40 mg
      during repeated oral administration in Helicobacter pylori-negative subjects.
AB  - BACKGROUND: Omeprazole has become available in a tablet formulation, a Multiple
      Unit Pellet System (MUPS) containing a large number of small individually enteric
      coated micropellets. AIM: To compare the acid-inhibitory effect of omeprazole
      MUPS 20 mg with pantoprazole 40 mg and to describe the pharmacokinetics of both
      drugs following administration on day 1 and day 6. METHODS: Randomized, two-way
      crossover study. Sixteen Helicobacter pylori-negative healthy subjects, whose
      gastric acidity fell below pH 4 for 70% of a 24-h baseline period were included.
      Intragastric pH was measured continuously. RESULTS: On day 1 both drugs
      significantly raised median 24-h gastric pH compared to baseline. Median pH and
      percentages of time above pH 3 and 4 on day 1 and day 6 of administration were
      not significantly different, with the exception of median daytime pH on day 6,
      which was significantly higher with omeprazole (4.65 vs. 4.05). AUC and Cmax of
      omeprazole were significantly increased on day 6. AUC and Cmax of pantoprazole
      were not significantly increased. CONCLUSIONS: No significant difference in acid
      inhibitory effect on day 1. On day 6 median daytime pH was significantly higher
      with omeprazole MUPS, but the percentages of time spent above pH 3 and 4 were not
      significantly different. The significant increase in bioavailability of
      omeprazole may contribute to the increased effect on day 6.

PMID- 10930901
TI  - Equally high efficacy of 4, 7 and 10-day triple therapies to eradicate
      Helicobacter pylori infection in patients with ulcer disease.
AB  - BACKGROUND: In patients with ulcer disease the optimal dose and duration of
      Helicobacter pylori treatment containing omeprazole (O), metronidazole (M) and
      clarithromycin (C) has yet to be established. The efficacy might be influenced by
      metronidazole- and clarithromycin-resistance. AIM: To study the effect of
      duration of OMC treatment on its efficacy and influence of metronidazole
      resistance and clarithromycin-resistance on the optimal duration. MATERIALS AND
      METHODS: Ulcer patients (n=76) were randomized to three double-blind treatments
      of 10 days: OMC 4 consisted of 4 days b.d. 20 mg omeprazole, 400 mg metronidazole
      and 250 mg clarithromycin switched over to 6 days b.d. 20 mg omeprazole and
      placebo antibiotics (n=27); OMC 7 consisted of 7 days b.d. omeprazole 20 mg,
      metronidazole 400 mg and clarithromycin 250 mg and 3 days b.d. omeprazole 20 mg
      and placebo antibiotics (n=25); OMC 10 consisted of 10 days b.d. omeprazole 20
      mg, metronidazole 400 mg and clarithromycin 250 mg (n=24). H. pylori was assessed
      by biopsies for culture and histology pre- and 4-6 weeks after OMC therapy.
      Metronidazole-resistance and clarithromycin-resistance were assessed by the E
      test. RESULTS: Intention-to-treat-eradication rates were: OMC 4, 96%; OMC 7, 92%;
      and OMC 10, 96% (N.S.). All of the three per protocol eradication rates were 100%
      (95% CI: 85.2-100). Of 75 isolates, 16 were metronidazole-resistant and one was
      clarithromycin-resistant. CONCLUSION: In H. pylori-positive ulcer patients, OMC 4
      is highly efficacious and as effective as OMC 7 and OMC 10. No influence of
      metronidazole-resistance or clarithromycin-resistance was observed.

PMID- 10930902
TI  - Ulcer-healing drugs are required after eradication of Helicobacter pylori in
      patients with gastric ulcer but not duodenal ulcer haemorrhage.
AB  - AIM: To study the efficacy of a 2-week anti-Helicobacter therapy in the healing
      of H. pylori-associated bleeding peptic ulcers. METHODS: Omeprazole 20 mg,
      clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to
      180 patients with H. pylori-associated bleeding peptic ulcers. Endoscopy was
      repeated 4 weeks after the eradication therapy to assess healing of the peptic
      ulcers. RESULTS: Repeat endoscopies were performed in 168 patients (42 gastric
      ulcer and 126 duodenal ulcer) who followed the protocol. Thirty-eight patients
      with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers
      healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs.
      duodenal ulcer: 98%; P=0. 035). No patients who were compliant to the study
      medications suffered from re-bleeding. Stepwise discriminant analysis
      demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best
      predicted healing of the peptic ulcers. CONCLUSIONS: Ulcer-healing drugs should
      be continued after a 2-week course of omeprazole-containing anti-Helicobacter
      therapy for gastric ulcers and large peptic ulcers that have bled, but can be
      omitted in most patients with a bleeding duodenal ulcer.

PMID- 10930904
TI  - Rabeprazole, amoxycillin and low- or high-dose clarithromycin for cure of
      Helicobacter pylori infection.
AB  - BACKGROUND: Rabeprazole sodium is a proton pump inhibitor. AIM: To evaluate the
      efficacy and safety of 1-week triple therapy with rabeprazole, amoxycillin and
      clarithromycin for the eradication of Helicobacter pylori. METHODS: A total of
      100 subjects with H. pylori were randomly divided into two groups of 1-week
      triple therapy with rabeprazole 10 mg b.d., amoxycillin 750 mg b.d. and either
      clarithromycin 200 mg b.d. (RAC400, n=50) or clarithromycin 400 mg b. d. (RAC800,
      n=50). Endoscopic examination with four biopsies (two specimens from the antrum
      and two from the gastric body) was performed. The status of H. pylori infection
      was determined using culture and histology (Giemsa stain) of the biopsy
      specimens. Sensitivity to clarithromycin was determined using the E-test: MIC > 8
      g/mL was considered to be resistant, whereas MIC < 2 g/mL was considered to be
      sensitive. Cure was defined as no evidence of H. pylori infection 1 month after
      completion of treatment. RESULTS: There were no significant differences in the
      clinical characteristics of the two groups. Eradication rates (intention-to-treat
      and per protocol, respectively) were: RAC400: 86% (95% CI: 76-95%) and 89% (95%
      CI: 80-97%); RAC800: 94% (95% CI: 87-100%) and 97% (95% CI: 94-100%). There was
      no significant difference between the eradication rates of either regimen. Three
      subjects with failed eradication in the RAC400 group were all infected with a
      clarithromycin-resistant strain before beginning the therapy. Haemorrhagic
      colitis was the only severe adverse event, which was observed in one patient in
      the RAC800 group. CONCLUSION: One-week triple therapy with rabeprazole,
      amoxycillin and low-dose clarithromycin is effective for the eradication of H.
      pylori infection.

PMID- 10930903
TI  - Pantoprazole versus one-week Helicobacter pylori eradication therapy for the
      prevention of acute NSAID-related gastroduodenal damage in elderly subjects.
AB  - AIM: To compare the efficacy of pantoprazole vs. a one-week Helicobacter pylori
      eradication therapy for the prevention of NSAID-related gastroduodenal damage.
      METHODS: Patients over 60 years old with symptoms and/or a history of ulcer who
      needed NSAID treatment were evaluated by endoscopy. H. pylori positive subjects
      who had no severe gastroduodenal lesions were randomized to take, concomitantly
      with NSAID therapy, either: (i) pantoprazole 40 mg daily plus amoxycillin 1 g
      b.d. and clarithromycin 250 mg b.d. for 1 week (35 subjects, Group PAC) or (ii)
      pantoprazole 40 mg daily for 1 month (34 subjects, Group P). Endoscopy was
      repeated after 1 month. RESULTS: A significantly higher incidence of severe
      gastroduodenal damage was found in Group PAC than in Group P (29% vs. 9%,
      P<0.05). The percentages of patients worsened, unchanged and improved after 1
      month were, respectively: Group PAC: 46%, 46%, and 9% and Group P: 7%, 65%, and
      29% (P<0.0008). The percentage of H. pylori-negative subjects was 89% in Group
      PAC and 52% in Group P (P=0.0009). The incidence of gastroduodenal damage was
      higher in Group PAC treatment failures than in cured patients (50% vs. 25.8%,
      P=ns). CONCLUSION: One month of pantoprazole was more effective than a proton
      pump inhibitor-based triple therapy in the prevention of gastroduodenal damage in
      elderly H. pylori-positive NSAID users.

PMID- 10930905
TI  - Cetraxate, a mucosal protective agent, combined with omeprazole, amoxycillin, and
      clarithromycin increases the eradication rate of helicobacter pylori in smokers.
AB  - BACKGROUND: Our previous study demonstrated that Helicobacter pylori eradication
      was less effective in smokers than in non-smokers. Cetraxate is an anti-ulcer
      drug that increases gastric mucosal blood flow. AIM: To evaluate the effect of
      cetraxate combined with new triple therapy for the eradication of H. pylori in
      smokers. METHODS: This study had a single-centre, double-blind, randomized non
      placebo design. A total of 106 consecutive H. pylori-positive smoking patients
      were randomly allocated to one of two regimens: one group received omeprazole (20
      mg), amoxycillin (1500 mg), and clarithromycin (600 mg) for 7 days (OAC, n=55).
      The other group recieved OAC plus cetraxate (600 mg) for 7 days (OAC + CET,
      n=51). The success of H. pylori eradication was evaluated by histology and the
      13C-urea breath test at 4 weeks after completion of treatment. RESULTS: By
      intention-to-treat analysis, the H. pylori eradication rate was 55% in the OAC
      group and 92% in the OAC + CET group (P<0.01). By per protocol analysis, the H.
      pylori eradication rate was 58% in the OAC group and 94% in the OAC + CET group
      (P<0.01). CONCLUSION: Cetraxate combined with new triple therapy increases the
      eradication of H. pylori in smokers.

PMID- 10930906
TI  - Nitric oxide formation in the dog sphincter of Oddi from nitric oxide donors as
      measured with in vivo micro-dialysis.
AB  - BACKGROUND: Nitric oxide (NO) is known to play an important role in neurally
      mediated relaxation of the sphincter of Oddi. AIM: We investigated whether NO
      donors, such as nitroglycerin or zwitterionic polyamine/NO, applied into the
      common bile duct or intravenously, may induce the relaxation of the sphincter of
      Oddi by producing NO in the anaesthetized dog. METHODS: NO production in the
      sphincter of Oddi was measured by detecting NO oxidation products (NO2- and NO3-)
      using micro-dialysis methods. RESULTS: Zwitterionic polyamine/NO and
      nitroglycerin applied into the common bile duct induced a marked increase in NO2-
      but not NO3-, in the sphincter of Oddi. Intravenous infusion of zwitterionic
      polyamine/NO and nitroglycerin induced little or no increase in NO2- formation.
      Nitroglycerin infused into either the common bile duct or intravenously
      administered produced relaxation of the sphincter of Oddi, but zwitterionic
      polyamine/NO had no effect on the sphincter of Oddi in spite of the increase in
      NO2- levels. CONCLUSIONS: Locally or systemically applied NO donors induce
      relaxation of the sphincter of Oddi by producing NO, although their mode of
      action differs in different analogues.

PMID- 10930907
TI  - Lifestyle measures and reflux.

PMID- 10930908
TI  - OAM for cure of Helicobacter pylori infection.

PMID- 10930909
TI  - Acid suppression and upper GI bleeding.

PMID- 10930910
TI  - Helicobacter pylori infection is a protective factor for bleeding gastric ulcers
      but not for bleeding duodenal ulcers in NSAID users.

PMID- 10930912
TI  - Urology and the Internet: an evaluation of internet use by urology patients and
      of information available on urological topics.
AB  - OBJECTIVE: To determine the use of the Internet by urological patients for
      obtaining information about their disease, and to conduct an evaluation of
      urological websites to determine the quality of information available. PATIENTS
      AND METHODS: Questionnaires about Internet use were completed by 180 patients
      attending a general urological outpatient clinic and by 143 patients attending a
      prostate cancer outpatient clinic. The Internet evaluation was conducted by
      reviewing 50 websites listed by the Hotbottrade mark search engine for two
      urological topics, prostate cancer and testicular cancer, and recording details
      such as authorship, information content, references and information scores.
      RESULTS: Of the patients actively seeking further information about their health,
      19% of the general urological outpatient group and 24% of the prostate cancer
      group used the Internet to obtain this information. Most websites were either
      academic or biomedical (62%), provided conventional information (95%), and were
      not referenced (71%). The information score (range 10-100) was 44.3 for
      testicular cancer and 50.7 for prostate cancer; the difference in scores was not
      significant. CONCLUSION: The use of the Internet by patients is increasing, with
      > 20% of urology patients using the Internet to obtain further information about
      their health. Most Internet websites for urological topics provide conventional
      and good quality information. Urologists should be aware of the need to
      familiarize themselves with urological websites. Patients can then be directed to
      high-quality sites to allow them to educate themselves and to help them avoid
      misleading or unconventional websites.

PMID- 10930913
TI  - The effect of intestinal urinary reservoirs on renal function: a 10-year follow
      up.
AB  - OBJECTIVE: To study the effect of the storage of urine in intestinal reservoirs
      on long-term renal function and the possible causes of deterioration. PATIENTS
      AND METHODS: Eighty-seven patients (aged 4-35 years) with bladder exstrophy who
      underwent reconstruction of the lower urinary tract using a bowel segment were
      enrolled in a prospective protocol. The glomerular filtration rate (GFR) was
      measured before and after surgery at 1, 2, 5 and 10 years using 51Cr
      ethylenediamine tetra-acetic acid. Patients with a decline in GFR of > 5% were
      investigated to identify the cause. RESULTS: Of 58 patients with a follow-up of >
      or = 10 years, 53 were evaluable, four having been lost to follow-up and one
      refusing to accept the protocol. In these 53 patients, the mean (SD) GFR
      decreased from 97. 9 (20.4) to 92.9 (23.6) mL/min/1.73 m2 (P = 0.24). However,
      this decrease was accounted for by 10 patients (19%) whose GFR fell by > or = 20%
      over the 10 years. The causes of renal deterioration in these 10 patients were;
      chronic retention and/or infection caused by inadequate catheterization in poorly
      compliant patients (five), uretero-ileal stenosis (one), a high-pressure
      reservoir (one) and uncertain causes (three). CONCLUSIONS: For 80% of the
      patients, the storage of urine in intestinal reservoirs did not change renal
      function for at least 10 years. However, approximately 20% of patients had some
      deterioration in renal function during the 10-year follow-up, usually from
      identifiable and remediable causes. The storage of urine in bowel does not appear
      to be inherently damaging to kidney function. Patients with an enterocystoplasty
      need regular monitoring of renal function; when deterioration is detected the
      urinary tract must be functionally assessed.

PMID- 10930914
TI  - Evaluation of the 1997 tumour, nodes and metastases classification of renal cell
      carcinoma: experience in 172 patients.
AB  - OBJECTIVE: To compare the prognostic relevance of the 1987 and 1997 tumour, nodes
      and metastases (TNM) systems for staging renal cell carcinoma (RCC) in predicting
      patient outcome. PATIENTS AND METHODS: A series of 172 consecutive patients with
      RCC who underwent radical nephrectomy from January 1990 to October 1997 was
      evaluated comparatively according to the 1987 and 1997 TNM classifications. The
      median (range) follow-up of the patients was 50 (19-112) months. The probability
      of survival was estimated by the Kaplan-Meier method, using the log-rank test to
      estimate differences among levels of the analysed variables. RESULTS: Using the
      1997 TNM classification resulted in a redistribution of 99 patients from stage
      pT2 on the 1987 TNM classification to stage pT1. As the staging criteria for pT3
      and pT4 did not change, there was no re-classification of these patients. Kaplan
      Meier survival curves showed a similar separation in 5-year survival between
      stage pT1 and pT2 using both systems; 100% vs 80% for the 1987 TNM and 86% vs 69%
      for the 1997 TNM systems. This difference in survival rates between patients with
      pT1 and pT2 disease was statistically significant only for the 1997 TNM staging
      system. However, when the 1987 TNM staging classification was applied, the
      separation in 5-year survival rates between pT2 and pT3 disease was greater.
      CONCLUSION: This study confirms the prognostic relevance of the 1987 TNM system,
      as established in the present patients. The 1997 TNM classification resulted in a
      better stratification of patients with pT1-pT2 disease, but had similar
      prognostic value for pT2 and pT3 disease.

PMID- 10930915
TI  - Poor prognosis associated with thrombocytosis in patients with renal cell
      carcinoma.
AB  - OBJECTIVES: To better define the relationship between platelet count and survival
      using a retrospective analysis in patients with thrombocytosis and metastatic
      renal cell carcinoma (RCC), some of whom had a shorter life expectancy than those
      with a normal platelet count. PATIENTS AND METHODS: The records were reviewed of
      patients with stage IV RCC who had undergone a variety of adjuvant therapies
      after nephrectomy between 1972 and 1992. Entry criteria included a tissue
      diagnosis of RCC, at least one platelet count and a complete follow-up until the
      time of death. Of 350 patients available for review, 259 met the entry criteria.
      Patients were divided into two groups: group 1 included 112 patients whose
      platelet counts remained at < 4 x 105/microL between the time of nephrectomy and
      the time of death; group 2 included 147 patients with at least one platelet count
      of > 4 x 105/microL (mean age in each group 57 years). RESULTS: The mean (SD)
      survival for group 1 was 151 (34) months, compared with 92 (18) months for those
      in group 2. Using the log-rank chi-square test the difference in survival between
      the groups was significant (P = 0.005). Controlling for established prognostic
      indicators of pathological stage, nuclear grade and cell type, using Cox's
      regression technique, the difference in survival between the groups remained
      significant (P = 0.015). CONCLUSIONS: These results suggest that patients with
      metastatic RCC who receive adjuvant therapy and have a persistently normal
      platelet count have a 64% longer life expectancy than those with thrombocytosis.
      The difference is highly statistically significant when controlled for nuclear
      grade, cell type and pathological stage.

PMID- 10930917
TI  - The clinical implications of telomerase activity in upper tract urothelial cancer
      and washings.
AB  - OBJECTIVE: To measure telomerase activity in upper tract urothelial carcinomas
      (as renal pelvic tumours comprise nearly half of all kidney tumours in Taiwan, a
      much higher percentage than in other countries) and to determine whether
      telomerase activity could be used as an additional diagnostic marker in
      exfoliated cancer cells present in upper tract urothelial washing fluids, thus
      providing earlier diagnosis and treatment. Materials and methods Telomerase
      activity was assessed using the telomeric repeat amplification protocol assay in
      tissue samples from 31 upper tract urothelial carcinomas (from 29 patients). The
      feasibility of identifying cancer using telomerase activity in exfoliated cancer
      cells in 17 upper tract urothelial washing samples was also investigated.
      RESULTS: Telomerase activity was found in 30 (97%) of the 31 upper tract
      urothelial cancer tissue samples; telomerase activity was detectable in 95% of
      superficial cancers and in all 11 invasive tumours. The sensitivity of measuring
      telomerase activity was 100% for grade 1, 93% for grade 2 and 100% for grade 3
      tumours. In contrast, telomerase activity was detected in only two (8%) of 26
      normal adjacent tissue samples. When the telomerase activity of urothelial
      washing fluid was compared with that in the corresponding tumours, there was
      compatible telomerase activity in 15 of the 17 samples. Telomerase activity was
      more sensitive than voided urine cytology (15%) and washing fluid cytology (53%).
      In addition, the telomerase activity was high in metastatic lesions. CONCLUSION:
      Telomerase activity is present in most upper tract urothelial cancer tissues and
      may be present at an early stage of carcinogenesis. Telomerase activity can be
      detected in exfoliated cells in urothelial washing fluids in a high proportion of
      patients with upper tract urothelial cancer. These results suggest that measuring
      telomerase activity in the exfoliated cancer cells obtained from urothelial
      washing could be a potentially useful addition to the conventional diagnostic
      tools used to identify patients with upper tract urothelial carcinoma.

PMID- 10930916
TI  - Genetic identification of bilateral primary or metastatic nonpapillary renal cell
      carcinoma.
AB  - OBJECTIVE: To clarify the clonality of bilateral tumours by genetic analysis of
      bilateral renal cell carcinomas (RCCs) using the VHL gene, which is inactivated
      in approximately 60% of RCCs and which plays a causal role in the development of
      most cases of nonpapillary RCC. PATIENTS AND METHODS: The study included 20
      patients; seven had von Hippel-Lindau disease, three had papillary RCC and 10 had
      nonpapillary RCC. Paraffin-embedded blocks of tumour tissue were obtained from
      two of the three patients with papillary RCC and from nine of 10 with
      nonpapillary disease; all three exons of VHL were examined by direct sequencing.
      RESULTS: As reported previously, no VHL mutations were found in papillary
      tumours. However, in five of the nine nonpapillary cases, VHL mutations were
      identified in tumours on one or both sides. Three of the tumours had the same
      mutation on both sides, confirming a common origin. In the remaining two
      patients, the mutation status differed between the sides, confirming a bilateral
      primary origin. The former cases were characterized by a relatively large tumour
      on one side and multiple tumours on the other. CONCLUSIONS: In nonpapillary RCC
      multiplicity may suggest a metastatic origin. Such genetic information will be
      useful in treating and following patients with bilateral renal tumours.

PMID- 10930918
TI  - Safety and efficacy of transurethral resection of the prostate under
      sedoanalgesia.
AB  - OBJECTIVE: To assess the safety and efficacy of sedoanalgesia (local anaesthesia
      with sedation) in patients with benign prostatic hyperplasia (BPH) undergoing
      transurethral resection of the prostate (TURP). PATIENTS AND METHODS: The study
      comprised 50 patients with BPH, two-thirds of whom were graded III-IV using the
      American Society of Anesthesiologists system. All patients had a topical
      instillation of lignocaine jelly 2% into their urethra, combined with 1%
      lignocaine (100-200 mg) with 1 : 400 000 adrenaline infiltration of the prostate
      via the perineal route. Sedation and anxiolysis were obtained with the
      intramuscular pethidine (0.5 mg/kg) and promethazine (1 mg/kg). Standard TURP was
      then carried out, with pain monitored during surgery using a visual analogue
      scale (VAS, maximum 10 points) and the amount of analgesic required after TURP
      recorded. The amount of prostatic tissue excised, duration of surgery, blood
      requirement, catheter interval, complications and hospital stay were recorded.
      The effectiveness of TURP was assessed by comparing symptom scores, uroflowmetry
      and postvoid residual volume before and after surgery. RESULTS: The mean
      intraoperative VAS was < or = 1 at any time during or after surgery; no patient
      required any postoperative analgesics. Only two patients complained of discomfort
      during the procedure and even they were comfortable after a supplemental dose of
      pethidine (12.5 mg). There were no conversions to general or regional
      anaesthesia. No blood transfusion was required in any patient. All patients began
      a normal diet 30 min after surgery and all were discharged within 48 h of
      surgery. There were no deaths; one patient had transient urinary incontinence and
      three had mild urinary tract infection. CONCLUSION: Sedoanalgesia was an
      effective, safe and simple alternative to general or regional anaesthesia for
      TURP in patients with BPH.

PMID- 10930919
TI  - Does intraprostatic vasopressin prevent the transurethral resection syndrome?
AB  - OBJECTIVE: To determine whether intraprostatic vasopressin (IPVP) prevents the
      transurethral resection (TUR) syndrome during prostatectomy. PATIENTS AND
      METHODS: The study comprised 36 consecutive patients (mean age 68 years) with
      prostates clinically assessed as >/= 20 g who underwent standard transurethral
      prostatectomy (TURP). Ten units of vasopressin in 0.5 mL were diluted with 9.5 mL
      isotonic saline and injected into the prostate transrectally before TURP. Blood
      samples were taken before and immediately after TURP to measure serum sodium
      concentration and free haemoglobin levels. The TURP irrigant used was cooled,
      boiled water maintained at 70-80 cmH2O pressure during resection. Twenty patients
      had alcohol added to the irrigant and their breath alcohol assessed at 10-min
      intervals during TURP. All patients had their pulse rate, blood pressure and
      sensorium monitored continuously. Extreme care was taken to avoid and/or identify
      capsular damage during resection. RESULTS: The mean weight of tissue resected was
      36 g and the mean resection time 24 min. There was no significant change in
      clinical variables during TURP. In 19 patients the breath alcohol changes were
      insignificant. Changes in free haemoglobin were not significant, but the levels
      decreased after TURP in four patients, caused by the dilution consequent on the
      infusion of 800-1000 mL isotonic saline during surgery. Serum sodium
      concentrations showed only insignificant decreases, except in one patient whose
      breath alcohol suggested the absorption of 500 mL of irrigant. This patient's
      serum sodium concentration decreased by 9 mmol/L; 1 L of 5% dextrose was infused
      during the procedure and capsular damage was recognized early during TURP.
      CONCLUSION: Insignificant volumes of irrigant entered the circulation of the
      patients during TURP with water irrigation and IPVP. The greatest risk factor for
      fluid entry during TURP is capsular damage. IPVP decreases bleeding and therefore
      improves visibility, so allowing the early identification of capsular damage.
      IPVP seems therefore to be of help during TURP by decreasing bleeding and
      allowing insignificant volumes of irrigant to enter the vasoconstricted vessels;
      it appears to prevent the TUR syndrome.

PMID- 10930920
TI  - Five-year data from the Oxford Laser Prostatectomy Trial.
AB  - OBJECTIVE: To evaluate the natural history of a group of patients who underwent
      contact laser prostatectomy or transurethral resection of the prostate (TURP).
      PATIENTS AND METHODS: Patients were followed up at 5 years after enrolling in a
      prospective double-blind randomized controlled trial of TURP vs contact laser
      prostatectomy. RESULTS: Of the initial trial patients, 11.5% had died (seven in
      the laser and 10 in the TURP arm) and eight (5.4%) were too incapacitated by
      coexistent medical disease to respond to the questionnaires. Thirty-eight
      patients were not available for follow-up, despite numerous invitations. Thirteen
      of the laser patients (18%) and 11 of the TURP patients (14.5%) had undergone re
      operation. Two patients from each arm had received alpha-blockers for worsening
      symptoms. CONCLUSIONS: Five years after prostatic surgery, a significant number
      of patients were dead or disabled by coexistent medical disease. The re-operation
      rate after TURP and contact laser prostatectomy were similar.

PMID- 10930921
TI  - The role of colour Doppler ultrasonography in detecting prostate cancer.
AB  - OBJECTIVE: To determine the usefulness of colour Doppler ultrasonography (CDUS)
      in detecting prostate cancer, by comparing CDUS with grey-scale transrectal
      ultrasonography (TRUS) and magnetic resonance imaging (MRI). PATIENTS AND
      METHODS: In all, 278 patients who underwent prostate biopsies because of an
      abnormal digital rectal examination, elevated prostate specific antigen levels,
      and/or abnormal TRUS between May 1998 and November 1999 were evaluated. The
      diagnostic accuracies of TRUS, CDUS, MRI and combinations of these imaging
      techniques in detecting prostate cancer were compared, based on the biopsy
      results. RESULTS: Carcinoma was detected in 233 of 1696 specimens, and 87
      patients were diagnosed with prostate cancer. For each detected cancer site, the
      sensitivity of CDUS was lower than those of other imaging techniques, but CDUS
      had high a specificity and positive predictive value. The combination of grey
      scale TRUS and CDUS or MRI improved the sensitivity and negative predictive
      value. The specificity and positive predictive value of the combination of grey
      scale TRUS and MRI were less than those for grey-scale TRUS alone, while those
      for the combination of grey-scale TRUS and CDUS were higher than those for grey
      scale TRUS alone. Five tumours were isoechoic but seen as hypervascular lesions
      with CDUS. CONCLUSION: CDUS provides information useful for detecting prostate
      cancer when used in combination with grey-scale TRUS, and should be included in
      the routine examination for prostate cancer.

PMID- 10930922
TI  - The prognostic value of inducible nitric oxide synthase in local prostate cancer.
AB  - OBJECTIVE: To compare the clinical and histological data from patients with
      prostate cancer with the results of the immunohistochemical analysis of inducible
      nitric oxide synthase (iNOS), and thus determine the prognostic value of iNOS.
      PATIENTS AND METHODS: The study included 82 patients (mean age 64.6 years, SD
      6.1) with local prostate cancer treated by radical prostatectomy in two Finnish
      hospitals. Their mean (SD) follow-up was 3.3 (2.2) years. An immunohistochemical
      method was used to detect the expression of iNOS in these specimens, and the
      expression graded according to staining intensity as none, weak or strong.
      RESULTS: There was weak or strong expression of iNOS in 25 (31%) and 56 (68%) of
      the patients, respectively, and one specimen was negative for iNOS. Strong
      expression of iNOS was related to high a preoperative prostate specific antigen
      (PSA) level (P = 0.006) and high pT classification (P < 0.001), but not to nodal
      status, grade, seminal vesicle or capsular invasion, surgical margin status,
      perineural infiltration, tumour infiltrating lymphocytes or proliferation rate of
      cancer cells. A PSA failure was detected in 29 patients but was not predicted by
      iNOS expression. A Cox multivariate analysis showed that surgical margin
      positivity, seminal vesicle involvement and number of tumour infiltrating
      lymphocytes predicted the PSA failure. CONCLUSION: A high expression of iNOS was
      related to a high pT classification and the preoperative PSA level but not to
      other established prognostic factors; iNOS expression was not a predictor of PSA
      failure in patients with local prostate cancer.

PMID- 10930924
TI  - Changes in the toilet training of children during the last 60 years: the cause of
      an increase in lower urinary tract dysfunction?
AB  - OBJECTIVE: To analyse the changes in toilet training of children in Belgium in
      the last three generations and to seek a possible cause for the apparent increase
      in lower urinary tract dysfunction over that period. PATIENTS AND METHODS: A
      questionnaire (25 questions) was developed and completed by 321 people who had
      toilet-trained 812 children. The population was divided into three groups
      according to the age of those who trained the children. RESULTS: There has been a
      major change in toilet training in the last 60 years; the age at which toilet
      training began has been significantly postponed. One reason for starting
      training, i.e. bladder control during the afternoon nap (which can probably be
      considered as an indication of sufficient bladder capacity) has become less
      important. Season (summer) has become a more important factor, as has starting
      school. Training by bladder drill, formerly widely used, was progressively
      abandoned and a more liberal attitude adopted by the youngest parents.
      CONCLUSION: There seems to be good concordance between the programmes currently
      proposed for treating bladder dysfunction in children and the traditional bladder
      training methods used by parents 60 years ago. To start bladder training when the
      child stays dry during the afternoon nap and using bladder drill might help to
      avoid permanent bladder dysfunction. The lack of formal bladder training may be
      responsible for an increase in lower urinary tract dysfunction.

PMID- 10930923
TI  - Hormone-resistant prostate cancer with symptomatic pelvic tumours: patient
      survival and prognostic factors.
AB  - OBJECTIVES: To determine the survival and investigate the prognostic significance
      of immunohistochemical variables and clinical factors in patients with hormone
      resistant prostate cancer (HRPC) and symptomatic pelvic tumours, in whom
      preliminary observations indicated that survival exceeded the median 8-10 months
      of patients with HRPC and painful bone metastases. PATIENTS AND METHODS: Seventy
      five patients with HRPC referred for palliative pelvic radiotherapy between 1980
      and 1996 were identified. For all patients at least two prostate biopsies had
      been obtained, one before primary hormone treatment and at least one after
      clinical progression despite androgen deprivation (HRPC biopsy). Bone scans at
      the time of referral were assessed. The medical records were reviewed for
      clinical variables of possible prognostic significance. Histological grade was
      recorded, and prostate-specific antigen (PSA), androgen receptors (ARs), Ki-67
      and p53 determined immunohistochemically. In 18 HRPC specimens the degree of AR
      amplification was analysed. RESULTS: Positive staining for ARs was high in the
      HRPC biopsies, although there was no association with AR amplification. Ki-67
      positivity increased after the development of HRPC. The median (range) survival
      was 14 (1-141) months; age < 65 years was associated with increased survival. In
      a multivariate analysis the following variables remained independent prognostic
      factors for survival from the time of the HRPC biopsy: bone metastases (0-10 vs >
      10 lesions, P < 0.001), low Ki-67 score (0 vs 1-3, P = 0.006) and low p53
      positivity score (0 vs 1-3, P = 0.014) in the HRPC biopsy. CONCLUSIONS: The
      median survival of patients with HRPC and pelvic tumours requiring palliation
      seems to exceed that of patients with HRPC and dominating painful bone metastases
      by at least 4-6 months. Simple clinical (bone metastases) and immunohistochemical
      variables (Ki-67, p53) enable patients with particularly long survival times to
      be identified, and in whom palliative treatment needs to be improved.

PMID- 10930925
TI  - Long-term follow-up of female patients with congenital adrenal hyperplasia from
      21-hydroxylase deficiency, with special emphasis on the results of vaginoplasty.
AB  - OBJECTIVE: To assess, in a long-term follow-up, female patients with congenital
      adrenal hyperplasia (CAH), with special emphasis on vaginal functional outcome
      and sexual activity after vaginoplasty. PATIENTS AND METHODS: Twenty-seven
      patients with CAH (aged 14-33 years; six Prader grade II, 14 grade III, six grade
      IV and one grade V) underwent surgery between 1972 and 1988. Three of the
      patients underwent clitoridectomy, 24 clitoroplasty and 25 vaginoplasty (24 with
      a Fortunoff flap and one a 'pull-through' procedure). In 20 patients the
      vaginoplasty was a one-stage procedure, undertaken at a mean (range) age of 3.6
      (1-9) years, and in five patients a two-stage operation. The analysis was based
      on the patients' history and examination; the patients also completed a
      questionnaire, including a psychological profile. RESULTS: Nine of the 25
      patients (36%) who underwent vaginoplasty developed intravaginal stenosis; of
      these nine, six were Prader grade III and three grade IV. All had undergone a
      single-stage procedure at a mean (range) age of 4.7 (2-9) years. Of the 16
      patients who answered the questionnaire, 14 had problems with their overall body
      image; patients in whom vaginal stenosis was corrected were particularly anxious
      about sexual intercourse and had problems with orgasm. CONCLUSION: The main
      problem during the long-term follow-up was intravaginal stenosis; all the
      affected patients had undergone a single-stage procedure early in life to correct
      ambiguous genitalia. This high rate of vaginal stenosis suggests that
      vaginoplasty should be undertaken at the beginning of puberty, because higher
      oestrogen levels may prevent stenosis and, if necessary, dilatation can be
      performed by the patient. These data also underscore the importance of
      psychological support in the treatment of children with CAH.

PMID- 10930926
TI  - Editorial comment

PMID- 10930928
TI  - Medicolegal issues and urology

PMID- 10930927
TI  - Paediatric lower urinary tract rhabdomyosarcoma: a single-centre experience of 30
      patients.
AB  - OBJECTIVE: To retrospectively analyse the long-term outcome of children with
      bladder and/or prostate rhabdomyosarcoma who were diagnosed at the authors'
      institution over the last 17 years. PATIENTS AND METHODS: The study comprised 30
      children (26 boys and four girls, mean age 5 years, range 15 days to 15 years);
      23 had stage III and seven had stage II disease. The initial biopsy showed an
      embryonal variant in 27 and round-cell sarcoma in three patients. All patients
      received eight weekly doses of vincristine, actinomycin D and cyclophosphamide
      (VAC). Subsequent treatment depended upon the response to chemotherapy. RESULTS:
      Fourteen patients had a complete or partial response to chemotherapy (> 50%
      reduction in tumour size); they were maintained on VAC chemotherapy for 2 years.
      Twelve patients in this group survived with no evidence of disease for 7 months
      to 10 years. Additional therapies were used in three patients, i.e. radical
      cystectomy in one and external irradiation in two. Sixteen patients had a minimal
      response to chemotherapy; in six, radical cystectomy was feasible and was
      followed by one year of chemotherapy. All patients were free of disease for 4-11
      years. Radiotherapy was given to the remaining 10 patients; thereafter radical
      cystectomy became feasible in five while partial cystectomy was possible in
      three. Only three of these 10 patients survived for 4-11 years. CONCLUSION: The
      tumour response to initial chemotherapy can be used to stratify patients into two
      risk-groups, i.e. low-risk patients with a complete or partial response in whom
      the bladder could be salvaged, and high-risk patients with a minimal response, in
      whom intensive treatment should be pursued, with no attempt at bladder salvage.

PMID- 10930929
TI  - Malpractice risks for urologists.

PMID- 10930930
TI  - Risk management and medicolegal issues in urology.

PMID- 10930931
TI  - Legal aspects of consent.

PMID- 10930932
TI  - What is negligence?

PMID- 10930933
TI  - Medical records and the law.

PMID- 10930934
TI  - Expert evidence: do you have all the facts?

PMID- 10930935
TI  - The medical expert witness.

PMID- 10930936
TI  - Issues in the diagnosis of renal cell carcinoma.

PMID- 10930937
TI  - Legal pitfalls in the diagnosis of prostate cancer.

PMID- 10930938
TI  - Medicolegal cases relating to bladder outlet obstruction.

PMID- 10930939
TI  - Iatrogenic ureteric injury: common medicolegal pitfalls.

PMID- 10930940
TI  - Urethral injury.

PMID- 10930941
TI  - Medicolegal aspects of hypospadias.

PMID- 10930942
TI  - The first cut is the deepest? Medicolegal aspects of male circumcision.

PMID- 10930943
TI  - Vasectomy: common medicolegal pitfalls.

PMID- 10930944
TI  - Testicular, epididymal and vasal injuries.

PMID- 10930945
TI  - Torsion of the testis.

PMID- 10930946
TI  - Medicolegal aspects of vesicovaginal fistulae.

PMID- 10930947
TI  - A natural glanular meatus after 'Mathieu and a V incision sutured': MAVIS.

PMID- 10930948
TI  - A rare complex bladder exstrophy variant.

PMID- 10930949
TI  - Carcinoma of the prostate associated with dermatomyositis.

PMID- 10930950
TI  - The management of ureteric stones and laparoscopic ureterolithotomy: the
      Edinburgh experience'.

PMID- 10930951
TI  - Angiogenic peptides in prostate disease.

PMID- 10930952
TI  - Does the temperature of lignocaine hydrochloride gel affect instillation
      discomfort in the male urethra?

PMID- 10930953
TI  - The rectal administration of lidocaine gel and tolerance of transrectal
      ultrasonography-guided biopsy of the prostate: a prospective randomized placebo
      controlled study.

PMID- 10930954
TI  - Bcl-2 proto-oncogene expression in low- and high-grade prostatic intraepithelial
      neoplasia.

PMID- 10930955
TI  - Reply

PMID- 10930956
TI  - Focal changes in nerve, muscle and connective tissue in normal and unstable human
      bladder.

PMID- 10930957
TI  - Metallic stents for malignant and benign ureteric obstruction.

PMID- 10930958
TI  - Fatherhood with no apparent spermatozoa.

PMID- 10930959
TI  - Re: 'Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir'.

PMID- 10930961
TI  - Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir.
AB  - AIMS: To investigate the effect of the antiretroviral protease inhibitors
      saquinavir (soft gelatin capsule) and ritonavir on the pharmacokinetic properties
      and tolerability of sildenafil and to investigate the effect of sildenafil on the
      steady-state pharmacokinetics of saquinavir and ritonavir. METHODS: Two
      independent, 8 day, open, randomized, placebo-controlled, parallel-group studies
      (containing a double-blind crossover phase) were conducted at Pfizer Clinical
      research units (Canterbury, UK. and Brussels, Belgium). Twenty-eight healthy male
      volunteers entered each study. In each study, volunteers were randomized (n = 14
      per group) to receive sildenafil on day 1 followed by a 7-day treatment period
      (days 2-8) with saquinavir or placebo (Study I) or ritonavir or placebo (Study
      II). Sildenafil or placebo (Study I and Study II) was administered alternately on
      day 7 or day 8, depending on initial randomization. The effect of saquinavir and
      ritonavir on the pharmacokinetics of sildenafil and its primary circulating
      metabolite (UK-103, 320) and the effect of single-dose sildenafil on the steady
      state pharmacokinetics of saquinavir (1200 mg three times daily) and ritonavir
      (500 mg twice daily) were determined. The safety and tolerability of sildenafil
      coadministered with saquinavir or ritonavir were also assessed. RESULTS: Both
      protease inhibitors significantly increased Cmax, AUC, tmax and t(1/2) values for
      both sildenafil and UK-103, 320. Ritonavir showed a significantly greater effect
      than saquinavir with increases in sildenafil AUC and Cmax of 11-fold (95% CI:
      9.0, 12.0) and 3.9-fold (95% CI: 3.2, 4.9), respectively. This compared with
      increases of 3.1-fold (95% CI: 2.5, 4.0) and 2.4-fold (95% CI: 1.8, 3.3) for
      coadministration with saquinavir. In contrast, the steady-state pharmacokinetics
      of saquinavir and ritonavir were unaffected by sildenafil. The increases in
      systemic exposure to sildenafil and UK-103, 320 were not associated with an
      increased incidence of adverse events or clinically significant changes in blood
      pressure, heart rate or ECG parameters. CONCLUSIONS: These results indicate that
      both saquinavir and ritonavir modify the pharmacokinetics of sildenafil
      presumably through inhibition of CYP3A4. The more pronounced effect of ritonavir
      may be attributed to its additional potent inhibition of CYP2C9. No change in
      safety or tolerability was observed when sildenafil was coadministered with
      either protease inhibitor. However, given the extent of the interactions, a lower
      sildenafil starting dose (25 mg) should be considered for patients receiving
      saquinavir and it is recommended not to exceed a maximum single dose of 25 mg in
      a 48 h period for patients receiving ritonavir.

PMID- 10930960
TI  - Therapeutic potential of ischaemic preconditioning.

PMID- 10930962
TI  - Single and multiple dose pharmacokinetics of nelfinavir and CYP2C19 activity in
      human immunodeficiency virus-infected patients with chronic liver disease.
AB  - AIMS: To evaluate the single-dose and multiple-dose pharmacokinetics of
      nelfinavir and its active M8 metabolite in eight HIV-seropositive patients with
      liver disease, and to examine the relationship between CYP2C19 activity (genotype
      and plasma M8/nelfinavir metabolic ratio) and the severity of liver disease in
      these patients. METHODS: Nelfinavir was given as a single dose (500 or 750 mg) to
      patients beginning therapy and twice (500, 750 or 1000 mg) or three times (250 or
      750 mg) daily during chronic therapy. Single-dose pharmacokinetic values were
      used to predict multiple-dose regimens. Peak and total plasma exposures between 2
      4 microg ml-1 and 45-75 microg ml-1 h, respectively, and predose levels > 0.7
      microg ml-1 were targeted for multidose nelfinavir. Genotype was determined by
      analysis for CYP2C19*1, CYP2C19*2, and CYP2C19*3. Individuals were grouped
      according to their genotype, molar M8/nelfinavir AUC ratio (low: < 0.1,
      intermediate: 0.1-0.3, high > 0.3), and Child-Pugh classification for severity of
      liver disease. RESULTS: Nelfinavir pharmacokinetics were characterized by wide
      interindividual variability, low clearance (181-496 ml min-1 70 kg-1, n = 7), and
      prolonged half-life (5-20 h, n = 7). M8/nelfinavir AUC ratio increased 58% (n =
      4) and alpha 1-acid glycoprotein levels decreased up to 39% (n = 5) from single
      to multiple dosing. CYP2C19 activity was low (metabolic AUC ratio < 0.1) in four
      patients with moderate to severe liver disease even though they were genetically
      extensive CYP2C19 metabolizers (*1/*1 or *1/*2). Three patients required lower
      daily doses than the standard regimen of 750 mg every 8 h to achieve target
      concentrations and maintain virologic suppression at < 50 RNA copies ml-1 (up to
      20 months). CONCLUSIONS: Acquired CYP2C19 deficiency from moderate or severe
      liver disease resulted in decreased M8 formation. Long-term HIV suppression is
      possible using low nelfinavir doses in patients with liver disease.

PMID- 10930963
TI  - Pharmacokinetics of epimeric budesonide and fluticasone propionate after repeat
      dose inhalation--intersubject variability in systemic absorption from the lung.
AB  - AIMS: Pharmacokinetic variability is likely to be a significant factor
      contributing to the interindividual differences in dose requirements, anti
      inflammatory response and side-effects with inhaled corticosteroids (ICS), but
      there is limited information about the disposition of ICS during regular dosing
      with a pressurized metered dose inhaler (pMDI). This study uses a mixed effects
      modelling approach to quantify and compare the interindividual variability in
      pharmacokinetics of epimeric budesonide (BUD) and fluticasone propionate (FP)
      after repeat-dose inhalation. METHODS: This pharmacokinetic substudy was part of
      a previously published open-label, randomised, placebo-controlled, 7-period
      crossover study to evaluate the short-term effects on plasma cortisol levels of
      inhaled BUD (400, 800, 1600 microg twice daily) and FP (375, 750, 1000 microg
      twice daily) via pMDI in a group of healthy male volunteers. On the fifth day of
      each high-dose treatment period (BUD 1600 microg twice daily and FP 1000 microg
      twice daily), venous blood samples were collected in nine subjects prior to the
      last dose and at 15 min, 30 min, 1, 2, 4, 6 and 8 h postdose for measurement of
      plasma drug concentrations to determine the pharmacokinetics of epimeric BUD and
      FP following inhalation. Non-compartmental analysis and a mixed effects model
      were used to characterize the disposition profiles. RESULTS: Both drugs had a
      rapid absorption half-life (BUD 10 min vs FP 11.3 min), but quite different
      elimination half-lives (BUD 2.4 h vs FP 7.8 h). Although there were
      intraindividual differences in the handling of the 22R-and 22S-epimers of BUD,
      there were no consistent pharmacokinetic differences between the two enantiomers
      in the group as a whole. Consistent with previous reports of FP's higher volume
      of distribution (V) and lower systemic bioavailability (F), the V/F ratio was
      lower for BUD than FP (498 l vs 8100 l). The parameter with the greatest
      interindividual variability for both BUD and FP was the rate of systemic
      absorption from the lung. CONCLUSIONS: This is the first report describing the
      pharmacokinetics of epimeric BUD and FP after repeat dose inhalation via pMDI.
      Three observations may be of clinical relevance: (1) there is considerable
      intersubject variability in the rate of absorption of both drugs from the lung;
      (2) in some individuals there was a long t(1/2),z for BUD, resulting in higher
      and more sustained plasma drug levels in the 4-12 h postdose period than would be
      predicted from single-dose pharmacokinetic data; and (3) there is evidence of
      diurnal variation in FP pharmacokinetics, with higher-than-expected plasma drug
      concentrations in the morning compared with the evening.

PMID- 10930964
TI  - A model for size and age changes in the pharmacokinetics of paracetamol in
      neonates, infants and children.
AB  - AIMS: The aims of this study were to describe paracetamol pharmacokinetics in
      neonates and infants. METHODS: Infants in their first 3 months of life (n = 30)
      were randomised to sequentially receive one of three paracetamol formulations
      (dose 30-40 mg kg-1) over a 2 day period. The formulations were (a) elixir, (b)
      glycogelatin capsule suppository and (c) triglyceride base suppository.
      Approximately six blood samples were taken after each dose over the subsequent 10
      16 h. Data were analysed using a nonlinear mixed effect model. These neonatal and
      infant data were then included with data from four published studies of
      paracetamol pharmacokinetics (n = 221) and age-related pharmacokinetic changes
      investigated. RESULTS: Population pharmacokinetic parameter estimates and their
      coefficients of variation (CV%) for a one compartment model with first order
      input, lag time and first order elimination were volume of distribution 69.9
      (18%) l and clearance 13.0 (41%) l h-1 (standardized to a 70 kg person). The
      volume of distribution decreased exponentially with a half-life of 1.9 days from
      120 l 70 kg-1 at birth to 69.9 l 70 kg-1 by 14 days. Clearance increased from
      birth (4.9 l h-1 70 kg-1) with a half-life of 3.25 months to reach 12.4 l h-1 70
      kg-1 by 12 months. The absorption half-life (tabs) for the oral preparation was
      0.13 (154%) h with a lag time (tlag) of 0.39 h (31%). Absorption parameters for
      the triglyceride base and capsule suppositories were tabs 1.34 (90%) h, tlag 0.14
      h (31%) and tabs 0.65 (63%) h, tlag 0.54 h (31%), respectively. The tabs for
      elixir and capsule suppository in children under 3 months were 3.68 and 1.51
      times greater than children over 3 months. The relative bioavailability of rectal
      formulations compared with elixir were 0.67 (30%) and 0.61 (23%) for the
      triglyceride base and capsule suppositories, respectively. CONCLUSIONS: Total
      body clearance of paracetamol at birth is 62% and volume of distribution 174%
      that of older children. A target concentration above 10 mg l-1 in approximately
      50% subjects can be achieved by a dose from 45 mg kg-1 day-1 at birth and up to
      90 mg kg-1 day-1 in 5-year-old children. A reduced dose of 75 mg kg-1 day-1 in an
      8-year-old child is sufficient because clearance is a nonlinear function of
      weight.

PMID- 10930965
TI  - Validation of a population pharmacokinetic model for adjunctive lamotrigine
      therapy in children.
AB  - AIMS: This analysis was performed to validate a previously developed population
      pharmacokinetic model for lamotrigine in order to establish a basis for dosage
      recommendations for children. METHODS: (a) The importance of the covariates in
      the final model was confirmed using the model validation dataset. Population and
      individual (Bayesian estimate) pharmacokinetic parameters were estimated using
      both the initial model, which included none of the covariates, and the final
      model. Accuracy and precision of parameter estimation and of concentration
      prediction were compared between the two models. (b) The performance in
      predicting the validation concentrations by the final model parameters obtained
      previously from the model development dataset was assessed. (c) The parameters of
      the final model were refined using a dataset combining both the development and
      validation data. RESULTS: Prediction performance of the final pharmacostatistical
      model was superior to that of the initial model. The results of the validation
      confirmed that concomitant antiepileptic drugs that increased or reduced
      lamotrigine clearance in adults had similar effects in children. The validation
      also verified the linear relationship between weight and clearance. The
      previously seen small sex effect on clearance was found statistically
      insignificant. CONCLUSIONS: The current analysis confirmed the previous findings.
      To achieve the same concentrations, children receiving enzyme-inducing
      antiepileptic drugs without valproate require higher doses than those receiving
      valproate; and heavier children require higher doses.

PMID- 10930966
TI  - Plasma erythropoietin concentrations in patients receiving intensive platinum or
      nonplatinum chemotherapy.
AB  - AIMS: Platinum chemotherapy has been shown to have potent antineoplastic activity
      against various tumours, especially testicular, bladder, ovarian, head and neck
      cancers. This activity is accompanied by side-effects of nephrotoxicity and
      cumulative myelosuppression, the latter frequently presenting as severe anaemia.
      Cisplatin and carboplatin nephrotoxicity might lower erythropoietin (Epo)
      secretion and, by this mechanism, contribute to the anaemia that follows therapy
      with this chemotherapeutic agent. The aim of the present work is to study the
      plasma immunoerythropoietin and haemoglobin levels of cancer patients treated
      with platinum or 5-fluorouracil-based chemotherapy. METHODS: Plasma was obtained
      from 25 patients who were about to receive chemotherapy for advanced malignancy:
      15 treated with cisplatin or carboplatin and 10 with nonplatinum drugs. Blood was
      collected on the first day (before drug administration) and around day 15 of
      every chemotherapy course. Complete blood count, creatinine and immunoreactive
      Epo levels were also measured in 22 healthy volunteers. RESULTS: An increase in
      Epo levels occurred following every course of 5-FU or platinum based chemotherapy
      in patients with steady concentrations of creatinine and decreased levels of
      haemoglobin (Hb). In particular, we observed an increase after about 15 days of
      the chemotherapy treatment and the Epo levels declined toward normal just before
      the following course. This phenomenon was evident in every course. CONCLUSIONS:
      Our results suggest that chemotherapy administration, using the current standards
      of hydration and forced diuresis, slightly lowered Hb levels but did not depress
      Epo production, both in 5-FU and in platinum treated subjects.

PMID- 10930967
TI  - Effects of potassium channel opener KRN4884 on human conduit arteries used as
      coronary bypass grafts.
AB  - AIMS: The effects of a new potassium channel opener KRN4884 on human arteries
      have not been studied. This study was designed to investigate the effects of
      KRN4884 on the human internal mammary artery (IMA) in order to provide
      information on possible clinical applications of KRN4884 for preventing and
      relieving vasospasm of arterial grafts in coronary artery bypass grafting.
      METHODS: IMA segments (n = 140) taken from patients undergoing coronary surgery
      were studied in the organ chamber. Concentration-relaxation curves for KRN4884
      were established in the IMA precontracted with noradrenaline (NA), 5
      hydroxytryptamine (5-HT), angiotensin II (ANG II), and endothelin-1 (ET-1). The
      effect of glibenclamide (GBC) on the KRN4884-induced relaxation was also examined
      in NA or 5-HT-precontracted IMA. Concentration-contraction curves for the four
      vasoconstrictors were constructed without/with pretreatment of KNR4884 (1 or 30
      microM) for 15 min. RESULTS: KRN4884 induced less relaxation (P < 0.05) in the
      precontraction induced by ET-1 (72.9 +/- 5.5%) than by ANG II (94.2 +/- 3.2%) or
      NA (93.7 +/- 4.1%) with lower EC50 (P < 0.05) for ANG II (-8.54 +/- 0.54 log M)
      than that for NA (-6.14 +/- 0.15 log M) or ET-1 (-6.69 +/- 0.34 log M). The
      relaxation in the IMA pretreated with GBC was less than that in control (P <
      0.05). KRN4884-pretreatment significantly reduced the contraction (P < 0.05)
      induced by NA (151.3 +/- 18.4% vs 82.7 +/- 8. 7%), 5-HT (82.7 +/- 12.2% vs 30.1
      +/- 7.3%), and ANG II (24.3 +/- 6. 3% vs 5.4 +/- 1.6%), but did not significantly
      reduce the contraction induced by ET-1 (P > 0.05). CONCLUSION: KRN4884 has marked
      vasorelaxant effects on the human IMA contracted by a variety of vasoconstrictors
      and the effect is vasoconstrictor-selective.

PMID- 10930968
TI  - First trimester exposure to cefuroxime: a prospective cohort study.
AB  - AIMS: There are no published studies on the safety of cefuroxime use during
      pregnancy. We therefore investigated prospectively the possible teratogenic
      effect of intrauterine exposure to cefuroxime. METHODS: One hundred and six women
      who received cefuroxime during the first trimester of pregnancy were recruited
      from three teratogen information centres in Israel. Exposed women were paired for
      age, smoking habits and alcohol consumption with references being exposed to
      nonteratogenic antibiotics administered for the same indications. RESULTS:
      Maternal history, birthweight, gestational age at delivery, rates of live births,
      spontaneous abortions and fetal distress were comparable among the two groups.
      Rates of major malformations in the cefuroxime group (3.2%) did not differ from
      references (2%) (P = 0. 61, relative risk = 1.56, 95% confidence interval 0.27
      9.15). There was a significantly higher rate of induced abortions among the
      cefuroxime exposed women as compared to the references (P = 0.04, relative risk =
      3.33, 95% confidence interval 0.94-11.77). CONCLUSIONS: Our data may suggest that
      exposure to cefuroxime during the first trimester is probably not associated with
      an increased risk for malformations or spontaneous abortions; however, in light
      of the small sample size and the broad confidence limits, larger studies are
      needed to confirm these findings.

PMID- 10930969
TI  - Compliance with tricyclic antidepressants: the value of four different methods of
      assessment.
AB  - AIMS: To assess the advantages and disadvantages of four methods for studying
      compliance with antidepressants: self-report scores, tablet counts, a
      microprocessor (MEMS) container system and the assay of nordothiepin and
      dothiepin concentrations in plasma. METHODS: The techniques were used in 88
      patients commencing tricyclic antidepressants in the setting of UK general
      practice. RESULTS: The MEMS system proved to be the most informative technique
      allowing identification of the precise time of container opening, the
      demonstration of 'drug holidays' and early cessation of therapy. Self-report
      scores (Morisky) proved a useful screening technique with a sensitivity of 72.2%
      and specificity of 74.1% for > or = 80% compliance. Although tablet counts were
      possible in 84 patients (95. 5%) they were unreliable in 19 (21.6%). Blood
      concentration assays proved the least acceptable method to patients and were
      possible in only 53 (60.2%). A ratio of nordothiepin:dothiepin > or = 1.1
      claimed, by others, to identify noncompliance was only reliable when
      concentrations were low. CONCLUSIONS: Both the MEMS system and self-report scores
      proved useful methods for identifying noncompliant patients in the setting of UK
      general practice. Although compliance was higher than reported in previous
      studies with 70 patients (79.5%) completing 6 weeks treatment, general
      practitioners tended to prescribe subtherapeutic doses.

PMID- 10930970
TI  - Effects of a medicine review and education programme for older people in general
      practice.
AB  - AIMS: To determine whether a medicine review and education programme influences
      the compliance and knowledge of older people in general practice. METHODS: Older
      people taking at least three medicines were randomly allocated to a control or
      intervention group. Both groups received three visits from a clinical pharmacist:
      Visit 1: Assessment and patients' medicines rationalized in intervention group.
      Visit 2: Intervention group given medicines education. Visit 3: Knowledge and
      compliance in both groups assessed by structured questionnaire RESULTS:
      Compliance in the intervention group was 91.3%, compared with 79.5% in the
      control group (P < 0.0001). The number of intervention group patients correctly
      understanding the purpose of their medicines increased from 58% to 88% on the
      second visit, compared with 67% to 70% in the control group (P < 0.0005).
      CONCLUSIONS: A general practice based medication review and education programme
      improved medicine compliance and knowledge of older people in the short term.

PMID- 10930971
TI  - Pharmacokinetics and tolerability of intravenous infusion of adenosine (SUNY4001)
      in healthy volunteers.
AB  - AIMS: To examine the tolerability and disposition of i.v. adenosine (SUNY4001) in
      healthy male Japanese volunteers. METHODS: SUNY4001 was infused i.v. for 6 min at
      0 (placebo), 60, 100, 120 and 140 microg kg-1 min-1 in a dose-escalating manner
      in 30 healthy subjects. Adenosine and its metabolites were determined in the
      plasma and urine. RESULTS: Only plasma hypoxanthine was increased from 3 min
      during until 5-10 min after SUNY4001 infusion at the higher rates without any
      significant dose-related changes in plasma adenosine, inosine, xanthine or uric
      acid, or in urinary adenosine and all metabolites compared with the placebo.
      There was a dose-related increase in the incidence of subjective symptoms such as
      heat sensation, flushed face, dyspnoea, chest discomfort, etc. Transient and self
      subsiding episodes of second-degree atrioventricular block were found in two
      subjects each at the higher doses. CONCLUSIONS: Adenosine infusion at < or = 140
      microg kg-1 min-1 was concluded to be generally well tolerated.

PMID- 10930973
TI  - Increased osteoblastic activity in myelomatosis.

PMID- 10930974
TI  - The story of chronic myeloid leukaemia.

PMID- 10930972
TI  - Pharmacokinetic-pharmacodynamic evaluation of ceftazidime continuous infusion vs
      intermittent bolus injection in septicaemic melioidosis.
AB  - AIMS: Experimental studies have suggested that constant intravenous infusion
      would be preferable to conventional intermittent bolus administration of beta
      lactam antibiotics for serious Gram-negative infections. Severe melioidosis
      (Burkholderia pseudomallei infection) carries a mortality over 40% despite
      treatment with high dose ceftazidime. The aim of this study was to measure the
      pharmacokinetic and pharmacodynamic effects of continuous infusion of ceftazidime
      vs intermittent bolus dosing in septicaemic melioidosis. METHODS: Patients with
      suspected septicaemic melioidosis were randomised to receive ceftazidime 40 mg
      kg(-1) 8 hourly by bolus injection or 4 mg kg(-1) h(-1) by constant infusion
      following a 12 mg kg(-1) priming dose and pharmacokinetic and pharmacodynamic
      parameters were compared. RESULTS: Of the 34 patients studied 16 (59%) died.
      Twenty patients had cultures positive for B. pseudomallei of whom 12 (60%) died.
      The median MIC90 of B. pseudomallei was 2 mg l(-1), giving a minimum target
      concentration (4*MIC) of 8 mg l(-1). The median (range) estimated total apparent
      volume of distribution, systemic clearance and terminal elimination half-lives of
      ceftazidime were 0.468 (0.241-0. 573) l kg(-1), 0.058 (0.005-0.159) l kg(-1) h(
      1) and 7.74 (1.95-44.71) h, respectively. Clearance of ceftazidime and creatinine
      clearance were correlated closely (r = 0.71; P < 0.001) and there was no evidence
      of significant nonrenal clearance. CONCLUSIONS: Simulations based on these data
      and the ceftazidime sensitivity of the B. pseudomallei isolates indicated that
      administration by constant infusion would allow significant dose reduction and
      cost saving. With conventional 8 h intermittent dosing to patients with normal
      renal function, plasma ceftazidime concentrations could fall below the target
      concentration but this would be unlikely with a constant infusion. Correction for
      renal failure, which is common in patients with meliodosis is Clearance = k(*)
      creatinine clearance where k = 0.72. Calculation of a loading dose gives median
      (range) values of loading dose, DL of 18.7 mg kg(-1) (9.5-23) and infusion rate I
      = 3.5 mg k(-1) h(-1) (0.4-13) (which equals 84 mg kg(-1) day(-1)). A nomogram for
      adjustment in renal failure is given.

PMID- 10930975
TI  - Who may benefit from donor leucocyte infusions after allogeneic stem cell
      transplantation?

PMID- 10930976
TI  - Neutrophil production and function in newborn infants.

PMID- 10930977
TI  - Optimizing antimetabolite-based chemotherapy for the treatment of childhood acute
      lymphoblastic leukaemia.

PMID- 10930978
TI  - The modern management of severe aplastic anaemia.

PMID- 10930979
TI  - Modelling haemopoietic stem cell division by analysis of mutant red cells.
AB  - Data describing the number of human red cells mutated at the glycophorin A locus,
      measured flow cytometrically, are reported for 752 adults and 49 neonates. The
      variance increases with age more rapidly than the approximately linear increase
      in mean. It is postulated that this discrepancy is explained by the known
      property of asymmetric stem cell division, so that the division of a single
      mutant stem cell may result in zero, one or two progeny stem cells. A
      mathematical analysis allows description of this process with three parameters:
      stem cell number, mean division rate and mutation rate per division. The values
      of these parameters can not be deduced from the data presented here. However,
      estimates of either stem cell number or mutation rate from other sources enable
      deduction of the two other parameters. The mean number of divisions per stem cell
      per lifetime was estimated to be about 70. This analysis therefore implies that
      the rate at which blood cell telomeres shorten with age acts as a direct measure
      of stem cell turnover. Furthermore, it is argued that this low figure implies
      that mutations occurring during early life, including organogenesis, are
      relatively important in initiating stem cell-derived malignancy. Finally, the
      number of human stem cell divisions per lifetime is similar to shorter-lived
      mammals, suggesting this number is important in the ageing process.

PMID- 10930980
TI  - Stem cell factor and erythropoietin inhibit apoptosis of human erythroid
      progenitor cells through different signalling pathways.
AB  - Erythropoietin (EPO) and stem cell factor (SCF) are two important factors in
      human erythropoiesis. We have recently demonstrated that SCF and EPO
      synergistically activate mitogen-activated protein (MAP) kinase, thereby
      promoting growth of human erythroid colony-forming cells (ECFCs). In the present
      study, we have examined the intracellular mechanisms by which SCF and EPO
      maintain survival of these cells. In the absence of SCF and EPO, human ECFCs
      underwent rapid apoptosis. The process was significantly inhibited by addition of
      a single factor and was totally prevented in the presence of both factors.
      Treatment of ECFCs with wortmannin, a specific inhibitor of phosphoinositide 3
      kinase (PI3K), inhibited the antiapoptotic effect of SCF but had no effect on
      that of EPO, indicating that SCF but not EPO inhibits apoptosis through the PI3K
      pathway. In contrast, treatment of ECFCs with PD98059, a specific inhibitor of
      MAP kinase/ERK kinase (MEK), inhibited cell growth but had no effect on the
      antiapoptotic activity of either SCF or EPO, suggesting that SCF and EPO prevent
      apoptosis of human ECFCs independent of the extracellular signal-regulated kinase
      (ERK) pathway. Interestingly, both EPO and SCF induced activation of PI3K.
      However, through PI3K, SCF caused activation of protein kinase B (PKB), an anti
      apoptosis signal, whereas EPO led to activation of ERKs. Furthermore, the SCF-
      and EPO-maintained expression of antiapoptotic protein Bcl-XL was correlated with
      the activation of ERKs and was inhibited by PD98059, suggesting that Bcl-XL may
      not have a major role in preventing apoptosis of human ECFCs. Phosphorylated BAD
      was not affected by SCF, EPO or wortmannin. Taken together with our previous
      results, the present study indicates that SCF and EPO support survival and growth
      of human ECFCs through different signalling pathways and that they transduce
      distinctly different signals through activation of PI3K.

PMID- 10930981
TI  - Mobilization of CD34+ haematopoietic stem cells is associated with a functional
      inactivation of the integrin very late antigen 4.
AB  - The beta1 integrin very late antigen 4 (VLA-4) plays a central role in
      mobilization and homing of CD34+ cells. In this study, we examined the activation
      state of VLA-4 on CD34+ cells from bone marrow (BM) and peripheral blood (PB) by
      flow cytometry using a vascular cell adhesion molecule I-immunoglobulin (VCAM
      I/IgG) fusion protein as soluble ligand. In an intraindividual analysis, we found
      a significantly reduced affinity and avidity of the VLA-4 receptor on CD34+ cells
      from PB during granulocyte colony-stimulating factor (G-CSF)-enhanced marrow
      recovery in comparison with steady-state BM. Moreover, the amount of circulating
      CD34+ cells during marrow recovery was inversely related to the activation state
      but not to the expression level of VLA-4, suggesting that a modulation of the
      functional state of VLA-4 is involved in the mobilization of CD34+ cells.
      Moreover, VLA-4 function on CD34+ cells from BM was associated with the
      maturation state of CD34+ cells as high-affinity VLA-4 receptors were observed on
      the vast majority of more primitive CD34+ cells. In addition, we found that Mg2+
      ions as well as co-incubation of CD34+ cells with endothelial cells resulted in
      an activation of the VLA-4 receptor. In conclusion, modulation of the functional
      state of VLA-4 appears to be of relevance for the mobilization and homing of
      CD34+ haematopoietic stem cells.

PMID- 10930982
TI  - Erythropoietin-induced rheological changes of rat erythrocytes.
AB  - The effects of recombinant human erythropoietin (rhEPO) on red blood cell (RBC)
      rheological properties were investigated in rats. Rats received intramuscular
      injections of 150 U/kg/d rhEPO for 5 d, following which blood samples were
      obtained 1, 5 or 10 d later. RBC deformability was assessed by determining cell
      transit times through 5-microm micropores (CTA) and RBC shape recovery time
      constants via photometry, aggregation in plasma and dextran was measured by
      photometry and RBC electrophoretic mobility was determined in a cylindrical
      electrophoresis system. RBC aggregation was found to be significantly decreased
      on day 5 after rhEPO treatment (P < 0.05), yet was unchanged from control on days
      1 and 10. Mean RBC micropore transit times remained unchanged, but the
      distributions of transit times were altered; compared with control, the 5th
      percentiles on both days 1 and 5 were decreased and the 95th percentile on day 1
      was elevated. Electrophoretic mobility of RBCs in phosphate-buffered saline was
      significantly increased on day 5 after rhEPO treatment (P < 0.05), with mobility
      measurements in dextran 500 (MW = 500 kDa) solutions suggesting that the cells'
      surface properties related to the formation of a 'depletion layer' may be altered
      on day 1. These results indicate that the rheological behaviour of RBC as a
      consequence of rhEPO treatment are temporal and are affected by the presence of
      reticulocytes as well as by the average age of the circulating cells.

PMID- 10930983
TI  - Fas-mediated apoptosis of peripheral blood mononuclear cells in patients with
      hepatitis C.
AB  - In the present study, we demonstrated that a close relationship exists between
      hepatitis C virus (HCV) infection of peripheral blood mononuclear cells (PBMCs)
      and cell-surface Fas expression in patients with hepatitis C, and showed the
      possibility of PBMCs apoptosis via a Fas-mediated system. The expression of Fas
      on PBMCs was found by flowcytometric analysis to be significantly increased in
      these patients. In addition, the treatment of patients' PBMCs with anti-Fas
      antibody induced cell death, with nuclear condensation and fragmentation and
      cellular DNA fragmentation. These data indicate that the patients' PBMCs
      expressed a large amount of functional Fas on the cell surface and were
      susceptible to stimulation against Fas, causing apoptotic cell death. We then
      quantified the serum-soluble Fas ligand (sFasL), which was known to bind to Fas
      and induce the apoptotic signals into the sensitized cells. The patients' serum
      sFasL levels were significantly higher than those of normal subjects and showed a
      good negative correlation with their PBMC number. To demonstrate the correlation
      between Fas expression and HCV infection, nested reverse transcriptase polymerase
      chain reaction (RT-PCR) was performed to detect HCV RNA. Interestingly, HCV RNA
      was preferentially detected from Fas-positive cells but not from Fas-negative
      cells, which had been isolated from PBMCs by magnetic beads. These results
      suggest that HCV infection of PBMCs might induce Fas expression and additional
      stimulation such as sFasL might induce apoptosis in these Fas-expressing cells.
      These mechanisms, in addition to hypersplenism, may explain the decrease in the
      number of PBMCs observed in patients with chronic hepatitis C.

PMID- 10930984
TI  - HCV-associated thrombocytopenia: clinical characteristics and platelet response
      after recombinant alpha2b-interferon therapy.
AB  - Hepatitis C virus (HCV) has been proposed as a possible causative agent of
      chronic thrombocytopenia. We investigated HCV infection in a series of 51
      unselected Spanish patients with chronic acquired thrombocytopenia. Anti-HCV and
      HCV viraemia were detected in 13/51 (22.5%) of cases; this prevalence was
      particularly significant when compared with HCV seropositivity in age-matched
      controls (0.4%). Anti-HCV-positive patients, four men and nine women with a
      median age of 59.3 years (range 36-72), had a mean platelet count of 55.8 x 109/l
      (range 12-96). Only one of our HCV-positive thrombocytopenic patients had
      hypersplenism. Platelet-associated IgG (PAIgG) was negative, as measured by
      immunofluorescent flow cytometric analysis in 11/13 HCV-positive thrombocytopenic
      patients. Thus, thrombocytopenia in our HCV-positive patients appeared to be non
      autoimmune mediated. In six patients, a trial of recombinant alpha2b-interferon
      (IFN-alpha) given at a dose of 3 MU three times per week for 6-24 months gave a
      durable (> 1 year) and significant increase in platelet count in all six
      patients. The maximum increase occurred after 6 months of IFN-alpha therapy. In
      conclusion, the ability of IFN-alpha to increase platelet counts in HCV-positive
      thrombocytopenic patients supports mechanisms involving a direct role for HCV
      inhibiting platelet production.

PMID- 10930985
TI  - Hereditary thrombocythaemia is a genetically heterogeneous disorder: exclusion of
      TPO and MPL in two families with hereditary thrombocythaemia.
AB  - Hereditary thrombocythaemia (HT) is an autosomal dominant disorder with clinical
      presentation and complications resembling sporadic essential thrombocythaemia
      (ET). Mutations in the thrombopoietin (TPO) gene causing overproduction of TPO
      and elevated TPO serum levels have been found previously in three families with
      HT. Here, we present evidence for genetic heterogeneity by demonstrating that HT
      in a Spanish and a US family is caused by genes other than TPO. Affected family
      members in both families had normal TPO serum levels. Genetic linkage analysis
      with TPO microsatellite markers excluded TPO as the disease gene in the Spanish
      HT family, and sequencing of the TPO gene revealed no mutations in the propositus
      of the US family. To test a role for MPL, the gene for the TPO receptor, we
      identified three single nucleotide polymorphisms (SNP) and a novel polymorphic CA
      microsatellite marker. By linkage analysis, we excluded MPL as the cause of HT in
      the Spanish family. Interestingly, mapping of the CA microsatellite marker to a
      region 40.5 kb upstream of MPL revealed the presence of sequences from the TIE
      gene, which encodes a tyrosine kinase receptor expressed on megakaryocytes and
      endothelial cells. Thus, MPL and TIE are in close physical proximity, and the CA
      microsatellite described here will be a useful genetic marker for both genes.

PMID- 10930986
TI  - Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia
      rutaecarpa, on platelet plug formation in in vivo experiments.
AB  - In this study, platelet thrombi formation was induced by irradiation of
      mesenteric venules with filtered light in mice pretreated intravenously with
      fluorescein sodium. Rutaecarpine (200 microg/g) significantly prolonged the
      latent period of inducing platelet plug formation in mesenteric venules when it
      was intravenously injected. Rutaecarpine (200 microg/g) prolonged occlusion time
      by approximately 1.5-fold (control 127 +/- 29 vs. taecarpine 188 +/- 23 s).
      Furthermore, aspirin (250 microg/g) also showed a similar prolongation of the
      occlusion time in this experiment. On a molar basis, rutaecarpine was
      approximately twofold more potent than aspirin at prolonging the occlusion time.
      Furthermore, rutaecarpine was also effective in reducing the mortality of ADP
      induced acute pulmonary thromboembolism in mice when administered intravenously
      at doses of 25 and 50 microg/g. Intravenous injection of rutaecarpine (50
      microg/g) significantly prolonged the bleeding time by approximately 1.5-fold
      compared with normal saline in the severed mesenteric arteries of rats.
      Continuous infusion of rutaecarpine (5 microg/g/min) also significantly increased
      the bleeding time 1. 5-fold, and the bleeding time returned to baseline within 60
      min after cessation of rutaecarpine infusion. These results suggest that
      rutaecarpine has an effective anti-platelet effect in vivo and that it may be a
      potential therapeutic agent for arterial thrombosis, but it must be assessed
      further for toxicity.

PMID- 10930987
TI  - Increased platelet activation and abnormal membrane glycoprotein content and
      redistribution in myeloproliferative disorders.
AB  - Chronic myeloproliferative disorders (MPDs) are characterized by a high incidence
      of thrombohaemorrhagic complications, possibly caused by platelet dysfunction. In
      an attempt to define platelet functional abnormalities, we assessed the
      expression of activation-dependent membrane proteins in unstimulated and agonist
      [ADP and thrombin receptor-activating peptide (TRAP)]-stimulated platelets using
      quantitative whole blood flow cytometry in samples from 50 MPD patients and 30
      controls. The receptor densities of activation markers and glycoproteins (GPs)
      were quantified using standardized fluorescent beads. Compared with controls, the
      mean percentage of P-selectin-positive (15.3% vs. 7.2%; P < 0.001) and
      thrombospondin (TSP)-positive (6.6% vs. 3.7%; P = 0.003) platelets was increased
      in unstimulated platelets from patients. Patients having experienced a thrombotic
      event had a higher mean percentage of TSP-positive non-stimulated platelets than
      patients without a history of thrombosis (9.0% vs. 4.6%; P = 0.02) and a higher
      GPIV molecules of equivalent fluorochrome (MEF) value (33113 vs. 24471 MEF; P =
      0.02). Mean MEF values of monoclonal antibodies (mAbs) against GPIb (34055 vs.
      38945 MEF; P < 0.001) and GPIIb/IIIa (1416 vs. 1648 MEF; P < 0. 001) were
      significantly reduced among patients, whereas surface expression of GPIV was
      increased in patients (28273 vs. 16258 MEF; P < 0.001). In TRAP (10 micromol/l)
      stimulated whole blood, the MEF of P-selectin (9611 vs. 13293 MEF; P = 0.004) and
      CD63 (2385 vs. 5177 MEF; P < 0.001) and the ratio of PAC-1/GPIIb/IIIa MEF (0.98
      vs. 2. 00; P < 0.001) was reduced in patients, indicating either a reduced
      granule GP content or an intrinsic cellular defect in receptor-mediated granule
      secretion and activation of the GPIIb/IIIa complex. Expressed as the relative
      change of MEF compared with unstimulated platelets, TRAP induced decrease of GPIb
      (7.8% vs. 45%; P < 0.001) and increase of GPIIb/IIIa (49.1% vs. 95.7%; P < 0.001)
      and GPIV expression (17.8% vs. 55.2%; P < 0.001) was attenuated in patients.

PMID- 10930988
TI  - Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected
      patients with venous thromboembolism.
AB  - We determined the prevalence of factor V Leiden and of prothrombin G20210A
      mutations in a cohort of unselected outpatients (n = 748) referred for suspected
      deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis
      of similar studies was also performed. Based on the clinical presentation, the
      prevalence of factor V Leiden was 15.7% in the 83 patients with DVT and 14.1% in
      the 99 patients with PE compared with 5.3% in patients without DVT and/or PE
      (control group). The prevalence of the prothrombin G20210A mutation did not
      differ among the three groups (3.9% for controls, 4. 8% for DVT and 3.9% for PE
      patients). We then divided the 99 patients with PE by separately analysing those
      with PE but without DVT (n = 57) and those with PE and DVT (n = 42). Compared
      with the control group, the prevalence of factor V Leiden was 10.5%, odds ratio
      (OR) 2.10 [95% confidence interval (95% CI) 0.68-5.45] in patients with primary
      PE and 19.1%, OR 4.20 (95% CI 1.54-10.30) in patients with DVT and PE. For the
      prothrombin G20210A mutation, no statistically significant differences were found
      between the control group and the three other groups. In conclusion, our data and
      the pooled analysis indicate that patients with primary PE are less often
      affected by the factor V Leiden mutation. No statistically significant
      differences were observed between patients and controls for the prothrombin
      G20210A mutation.

PMID- 10930989
TI  - Activated protein C inhibits lipopolysaccharide-induced nuclear translocation of
      nuclear factor kappaB (NF-kappaB) and tumour necrosis factor alpha (TNF-alpha)
      production in the THP-1 monocytic cell line.
AB  - Activated protein C (APC) protects against sepsis in animal models and inhibits
      the lipopolysacharide (LPS)-induced elaboration of proinflammatory cytokines from
      monocytes. The molecular mechanism responsible for this property is unknown. We
      assessed the effect of APC on LPS-induced tumour necrosis factor alpha (TNF
      alpha) production and on the activation of the central proinflammatory
      transcription factor nuclear factor-kappaB (NF-kappaB) in a THP-1 cell line.
      Cells were preincubated with varying concentrations of APC (200 microg/ml, 100
      microg/ml and 20 microg/ml) before addition of LPS (100 ng/ml and 10 microg/ml).
      APC inhibited LPS-induced production of TNF-alpha both in the presence and
      absence of fetal calf serum (FCS), although the effect was less marked with 10%
      FCS. APC also inhibited LPS-induced activation of NF-kappaB, with APC (200
      microg/ml) abolishing the effect of LPS (100 ng/ml). The ability of APC to
      inhibit LPS-induced translocation of NF-kappaB is likely to be a significant
      event given the critical role of the latter in the host inflammatory response.

PMID- 10930990
TI  - Influence of the -675 4G/5G dimorphism of the plasminogen activator inhibitor 1
      promoter on thrombotic risk in patients with factor V Leiden.
AB  - Elevated plasminogen activator inhibitor 1 (PAI-1) levels are associated with
      venous thromboembolism, although their significance is unclear. PAI-1 levels are
      influenced by a PAI-1 promoter dimorphism (4G/5G), the 4G allele being associated
      with increased PAI-1 activity. We investigated whether the 4G allele influenced
      thrombotic risk by studying 99 symptomatic factor V (FV) Leiden heterozygotes and
      99 healthy subjects. The 4G allele was more prevalent among cases than among
      healthy subjects (chi2 = 8.00, P = 0.005) and the odds ratio (OR) for thrombosis
      associated with either heterozygosity or homozygosity for the 4G allele was 2.43
      (P = 0. 011). We conclude that carriership of the 4G allele was more prevalent in
      patients who already carried factor V Leiden than in control subjects without
      factor V Leiden.

PMID- 10930991
TI  - Regenerating normal B-cell precursors during and after treatment of acute
      lymphoblastic leukaemia: implications for monitoring of minimal residual disease.
AB  - We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained
      in continuous complete remission after treatment according to the Dutch Childhood
      Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time
      points during and after treatment [640 bone marrow (BM) and 600 blood samples] by
      use of cytomorphology and immunophenotyping for the expression of TdT, CD34, CD10
      and CD19. Additionally, 60 BM follow-up samples from six patients were subjected
      to clonality assessment via heteroduplex polymerase chain reaction (PCR) analysis
      of immunoglobulin VH-JH gene rearrangements. We observed substantial expansions
      of normal precursor B cells in regenerating BM not only after maintenance therapy
      but also during treatment. At the end of the 2-week intervals after consolidation
      and reinduction treatment, B-cell-lineage regeneration was observed in BM with a
      large fraction of immature CD34+/TdT+ B cells. In contrast, in regenerating BM
      after cessation of maintenance treatment, the more mature CD19+/CD10+ B cells
      were significantly increased, but the fraction of immature CD34+/TdT+ B cells was
      essentially smaller. Blood samples showed a profound B-cell lymphopenia during
      treatment followed by a rapid normalization of blood B cells after treatment,
      with a substantial CD10+ fraction (10-30%). Heteroduplex PCR analysis confirmed
      the polyclonal origin of the expanded precursor B cells in regenerating BM. This
      information regarding the regeneration of BM is essential for the correct
      interpretation of minimal residual disease studies.

PMID- 10930992
TI  - Prognostic impact of karyotypic findings in childhood acute lymphoblastic
      leukaemia: a Nordic series comparing two treatment periods. For the Nordic
      Society of Paediatric Haematology and Oncology (NOPHO) Leukaemia Cytogenetic
      Study Group.
AB  - The prognostic impact of acquired chromosome abnormalities was evaluated in a
      population-based consecutive series of 768 children (< 15 years of age) with
      acute lymphoblastic leukaemia (ALL). The study cohort included all cases of
      cytogenetically abnormal childhood ALL diagnosed between 1986 and 1997 in the
      five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The
      probability of event-free survival (pEFS) for the total cohort was 0. 72 +/-
      0.02. When comparing the two treatment periods of July 1986 to December 1991 and
      January 1992 to December 1997, a better survival was seen for the latter time
      period (pEFS of 0.69 +/- 0.02 vs. 0.76 +/- 0.02, P = 0.05). Hypodiploidy with
      less than 45 chromosomes, t(9;22)(q34;q11) and 11q23 translocations were
      associated with a dismal outcome during the whole study period (pEFS of 0.57 +/-
      0.12, 0.41 +/- 0.14 and 0.37 +/- 0.10 respectively). The poor prognostic
      influence of 11q23 rearrangements seemed to be restricted to infants and older
      children (> 10 years), who differed significantly from children aged 1-10 years
      in this regard (P < 0. 01). Patients with t(9;22)-positive ALL seemed to benefit
      from allogeneic bone marrow transplantation in first remission (P = 0.05). The
      pEFS for children with t(1;19)(q23;p13)-positive ALL was intermediate (0.63 +/-
      0.17), with a tendency to a better outcome for patients with the unbalanced
      variant der(19)t(1;19). Hyperdiploid ALL patients, subdivided into moderate
      hyperdiploidy (47-51 chromosomes), massive hyperdiploidy (52-60 chromosomes) and
      cases in the tri-/tetraploid range (> 60 chromosomes) had the best outcome in the
      last treatment period (pEFS of 0.81 +/- 0.06, 0.80 +/- 0.04 and 0.88 +/- 0.07
      respectively), unless t(1;19), t(8;14), t(9;22) or 11q23 translocations were
      present. In a multivariate analysis including white blood cell (WBC) count,
      immunophenotype, age, mediastinal mass, central nervous system involvement and
      leukaemia karyotype, only WBC and modal chromosome number were shown to be
      significant independent risk factors (P < 0.01).

PMID- 10930993
TI  - Constitutive expression levels of CD95 and Bcl-2 as well as CD95 function and
      spontaneous apoptosis in vitro do not predict the response to induction
      chemotherapy and relapse rate in childhood acute lymphoblastic leukaemia.
AB  - CD95 (Fas/APO-1) expression and function and Bcl-2 expression, as well as
      spontaneous apoptosis in vitro, have been shown to be predictive markers for the
      in vivo response to chemotherapy in acute myeloid leukaemia (AML). To determine
      the clinical significance of apoptosis-regulating factors in acute lymphoblastic
      leukaemia (ALL), we investigated cell samples of children with ALL who had been
      included in the German ALL Berlin-Frankfurt-Munster (BFM) study using flow
      cytometry for constitutive expression levels of CD95 (n = 110) and Bcl-2 (n =
      110). Furthermore, we determined the extent of spontaneous apoptosis in vitro (n
      = 102) and susceptibility to anti-CD95-induced apoptosis (CD95-sensitivity) (n =
      97). We correlated these findings with the functional activity of the multidrug
      resistance (MDR)-associated P-glycoprotein (P-gp), as detected by the
      rhodamine123 efflux test, immunophenotype, cytogenetics and clinical data of the
      patients examined. Good responders to initial prednisone therapy ('prednisone
      response') revealed significantly higher Bcl-2 expression levels [5.4 +/- 3.4
      relative fluorescence intensity (RFI), n = 68] than poor responders (3.7 +/- 2.6
      RFI, n = 42; P = 0.002). There was no significant correlation between the other
      investigated parameters and prednisone response. Moreover, neither the CD95 and
      Bcl-2 expression levels nor the extent of spontaneous apoptosis in vitro, CD95
      sensitivity or P-gp function were correlated with the response to induction
      chemotherapy or relapse rate, either for B-cell precursor ALL or T-cell ALL. No
      consistent pattern of change in CD95 (n = 10) and Bcl-2 expression (n = 9) was
      noted in cases studied at both initial diagnosis and relapse. In conclusion, our
      findings underline the different cell biological features of primary AML and ALL
      cells.

PMID- 10930994
TI  - In vitro inhibition of cytidine triphosphate synthetase activity by cyclopentenyl
      cytosine in paediatric acute lymphocytic leukaemia.
AB  - Cytidine triphosphate (CTP) synthetase is a key enzyme for the synthesis of
      cytosine (deoxy)ribonucleotides, catalysing the conversion of uridine
      triphosphate (UTP) into CTP, and has a high activity in several malignancies. In
      this preclinical study, the enzyme activity and mRNA expression of the enzyme and
      (deoxy)ribonucleotide concentrations were analysed in leukaemic cells of 57
      children suffering from acute lymphocytic leukaemia (ALL). In addition, in vitro
      experiments were performed with the CTP synthetase inhibitor cyclopentenyl
      cytosine (CPEC). A significantly higher activity of CTP synthetase (6.5 +/- 3.9
      nmol CTP/mg/h) was detected in ALL cells than in lymphocytes of healthy controls
      (1.8 +/- 0.9 nmol CTP/mg/h, P < 0.001) that was independent of white blood cell
      (WBC) count, blast percentage, age, gender or type of ALL. The enzyme activity
      was not correlated with the CTP synthetase mRNA expression. The activity of CTP
      synthetase in ALL cells compared with non-malignant CD34+ bone marrow controls
      (5.6 +/- 2.4 nmol CTP/mg/h) was not statistically different. In vitro treatment
      of ALL cells with CPEC induced a dose-dependent decrease of the CTP
      concentration. The lowest concentration of CPEC (0.63 microM) induced a depletion
      of CTP of 41 +/- 20% and a depletion of dCTP of 27 +/- 21%. The degree of CTP
      depletion of ALL cells after treatment with CPEC was positively correlated with
      the activity of CTP synthetase. The inhibition of CTP synthetase in situ was
      confirmed by flux studies using radiolabelled uridine. From these results, it can
      be expected that CPEC has a cytostatic effect on lymphoblasts of children with
      ALL.

PMID- 10930995
TI  - The pharmacodynamic basis for the increased antileukaemic efficacy of cytosine
      arabinoside-based treatment regimens in acute myeloid leukaemia with a high
      proliferative activity.
AB  - The current study was initiated to explore the mechanisms underlying the
      previously demonstrated association between the proliferative activity of
      leukaemic blasts and the response to cytosine arabinoside (AraC)-based therapy in
      de novo acute myeloid leukaemia (AML). The activity of key enzymes of AraC
      metabolism-deoxycytidine kinase (DCK), cytidine deaminase (DCD) and polymerase
      alpha (PolyA) were determined in blast cells from 33 patients. In addition,
      formation and retention of intracellular levels of AraC triphosphate (AraCTP) and
      DNA incorporation of AraC were measured, as was the proliferative activity of
      leukaemic blasts by [3H]-TdR incorporation before and after stimulation with
      granulocyte-macrophage colony-stimulating factor (GM-CSF) or granulocyte CSF (G
      CSF) for 48 h. AraC incorporation into the DNA (median 0.60 pmol/105 cells) was
      significantly related to the proliferative activity of AML blasts (r = 0.74, P <
      0.001). Similarly, priming with GM-CSF or G-CSF increased both the proliferative
      activity of AML blasts by a median of 1.84- and 1.64-fold, respectively, and the
      incorporation of AraC into the DNA (1.29- and 1.40-fold respectively). In
      contrast, no relationship was found between the endogenous proliferative activity
      (EPA) and enzyme activities regulating AraC activation (DCK; median 4.70
      pmol/min/mg protein), inactivation (DCD; median 2.92 pmol/min/mg protein) or
      inhibitory effects (PolyA; median 1.50 pmol/min/mg protein), nor the formation or
      retention of AraCTP (median 306.1 ng/107 cell and 1.6 h respectively). When
      samples were grouped according to EPA (more than or less than the median), slowly
      proliferating specimens had a higher response to cytokine priming for
      proliferative activity and incorporation of AraC into DNA. Clinical data of 15
      patients were available. Although all eight patients with a high endogenous
      proliferative activity reached complete remission, only four out of seven
      patients with a low proliferative activity responded, whereas the other three
      patients were non-responders (P = 0.077).

PMID- 10930996
TI  - p53 allele deletion and protein accumulation occurs in the absence of p53 gene
      mutation in T-prolymphocytic leukaemia and Sezary syndrome.
AB  - In a series of 24 patients with chronic T-lymphoid disorders [13 T-prolymphocytic
      leukaemia (T-PLL) and 11 Sezary syndrome] we have studied (i) chromosome 17p
      abnormalities and p53 allele deletion by fluorescence in situ hybridization; (ii)
      mutation in the exons of the p53 gene by direct DNA sequencing; and (iii) p53
      protein expression by immunocytochemistry and, in some cases, also by flow
      cytometry with DO-1, a monoclonal antibody to the p53 protein. The study revealed
      p53 deletion and accumulation of p53 protein in the absence of mutation in the
      exons that included the hot-spots and differs from that described in B
      prolymphocytic leukaemia. Seven T-PLL and five Sezary syndrome patients had p53
      overexpression, and five T-PLL and nine Sezary syndrome patients showed p53
      deletion. Although the majority of cases with p53 accumulation had p53 deletion,
      the proportion of cells with the deletion did not correlate with the proportion
      of cells positive for p53 expression. Two cases of T-PLL showed strong p53
      expression in the absence of p53 deletion, and one case of Sezary syndrome with
      p53 deletion in 97% of cells did not express p53. These findings suggest that a
      non-mutational mechanism exists for the accumulation of p53 protein in these T
      cell disorders. The oncogenic effect of the accumulating wild-type protein has
      been reported in other malignancies. Whether haploidy resulting from p53 deletion
      contributes to this mechanism has yet to be determined. Alternatively, the
      frequent loss of the p53 gene could be associated with the deletion of an
      adjacent gene, which could be involved in the pathogenesis of these diseases.

PMID- 10930997
TI  - In vitro and in vivo effects of 2'-deoxycoformycin (Pentostatin) on tumour cells
      from human gammadelta+ T-cell malignancies.
AB  - Hepatosplenic gammadelta+ T-cell lymphoma represents a rare neoplasm of post
      thymic phenotype, characterized by an aggressive clinical course and a poor
      response to conventional chemotherapy. In the present study, we have examined the
      cytotoxic effects of the purine analogue 2'-deoxycoformycin (dCF) on cultured
      mononuclear cells and purified gammadelta+ tumour cells from bone marrow or
      peripheral blood of four patients with hepatosplenic gammadelta+ T-cell lymphoma.
      At a concentration of 10 microM, dCF, in the presence of 2'-deoxyadenosine
      (dAdo), displayed an early and selective cytotoxic effect on gammadelta+ tumour T
      cells. After 48 h of in vitro exposure to dCF, the absolute number of viable
      CD3+/gammadelta+ tumour T cells was reduced by more than 90% in all samples with
      respect to control cultures, with absolute counts of viable CD3+/alphabeta+
      lymphocytes being reduced only by 6-40% of the initial cell input. Analysis of
      cultures after 5 d of exposure to dCF plus dAdo revealed the persistence of
      normal CD3+/alphabeta+ T cells, which accounted, however, for only 20-25% of the
      initial cell input. Accordingly, the combination of dCF (10-100 microM) plus dAdo
      was able to induce a dose-dependent inhibition of clonogenic growth and [3H]
      thymidine incorporation in purified CD3+/CD4-/CD8- gammadelta+ tumour cells. We
      also report that one patient with hepatosplenic gammadelta+ T-cell lymphoma in
      terminal leukaemic phase showed a striking haematological response to single
      agent dCF given as fourth-line treatment. In particular, the selective clearance
      of gammadelta+ tumour T cells in peripheral blood and bone marrow was observed
      starting after the second course of treatment. Our results suggest that dCF may
      represent a potentially active drug for the management of this aggressive form of
      T-cell lymphoma.

PMID- 10930998
TI  - Post-transplantation lymphoproliferative disease of natural killer cell lineage:
      a clinicopathological and molecular analysis.
AB  - Post-transplantation lymphoproliferative disorders (PTLD) occur after solid organ
      and bone marrow transplantation. They are predominantly of B-cell and
      occasionally of T-cell lineage. We report a case of PTLD of natural killer (NK)
      cell lineage. A renal allograft recipient developed progressive pancytopenia 1
      year after transplantation. Serial bone marrow biopsies showed an increasing
      infiltration by large granular lymphoid cells. A subsequent leukaemic phase also
      developed with systemic infiltration of other organs. Immunophenotyping showed
      that these cells were CD2+, CD3-, CD3epsilon+, CD56+, CD94+, CD158a- and CD158b-.
      In situ hybridization showed Epstein-Barr virus (EBV) infection of the neoplastic
      cells. Genotypical analysis showed the T-cell receptor gene in germline
      configuration and clonal EBV episomal integration. The overall features were
      consistent with NK cell lymphoma/leukaemia. The patient did not respond to
      cessation of immunosuppression or anti-EBV treatment. Combination chemotherapy
      was given, but the patient died ultimately of disseminated fungal infection. In
      conclusion, we have demonstrated that NK cell lymphoma is another rare type of
      PTLD that appears to be highly aggressive and therefore may require early
      chemotherapy to improve treatment outcome.

PMID- 10931000
TI  - Generation of the NUP98-HOXD13 fusion transcript by a rare translocation,
      t(2;11)(q31;p15), in a case of infant leukaemia.
AB  - We report a case of de novo acute myelomonocytic leukaemia with the
      t(2;11)(q31;p15) translocation in a Japanese female infant. The NUP98-HOXD13
      fusion transcript generated by the translocation was detected in the patient's
      bone marrow cells by reverse transcription-polymerase chain reaction (RT-PCR).
      Additionally, ectopic expression of the normal allele of the HOXD13 gene was
      observed in this patient, suggesting that it might be associated with
      leukaemogenic development. This case is the third report of t(2;11) leukaemia
      with NUP98-HOXD13 and the first report showing that NUP98 rearrangements are
      associated with infant leukaemia, as well as therapy-related acute myelogenous
      leukaemia or myelodysplastic syndrome.

PMID- 10930999
TI  - T-cell expansions in patients with multiple myeloma have a phenotype of cytotoxic
      T cells.
AB  - The presence of T-cell clones in peripheral blood has been previously shown to be
      associated with a survival advantage in patients with multiple myeloma and
      suggests that the expanded T-cell populations may be involved in an anti-tumour
      response. We studied the T-cell receptor (TCR) repertoire of 38 patients with
      myeloma to identify and characterize the expanded T-cell populations by flow
      cytometry. T-cell expansions were found in 79% of the patients. The expansions
      occurred randomly among the 21 variable regions of the TCR beta chain (Vbeta)
      studied, representing 62% of the V-beta repertoire, and were stable during an 18
      month follow-up. The phenotype of the expanded V-beta populations was
      predominantly CD8+, CD57+, CD28- and perforin+, which differed significantly from
      the other non-expanded Vbeta populations. The expression of the apoptosis markers
      Fas (CD95) and bcl-2 were similar between the expanded and non-expanded Vbeta
      populations. In conclusion, expanded T-cell populations were frequent in patients
      with myeloma, they remained unchanged during follow-up and had phenotypic
      characteristics of cytotoxic T cells. These data add further support to the
      concept that the T-cell expansions may have an immunoregulatory role in myeloma.

PMID- 10931001
TI  - Deletion of the 5'-ABL region: a recurrent anomaly detected by fluorescence in
      situ hybridization in about 10% of Philadelphia-positive chronic myeloid
      leukaemia patients.
AB  - Inclusion of the BCR-ABL ES probe in routine cytogenetics led to the
      identification of a subgroup of Philadelphia positive (Ph+) chronic myeloid
      leukaemia patients characterized by a 5'-ABL deletion. This anomaly was observed
      in 5/51 cases (9.8%). Cytological and clinical data suggest that the 5'-ABL
      deletion may be associated with dysplastic features of polymorphonuclear cells
      and metamyelocytes and a short chronic phase duration.

PMID- 10931003
TI  - Anti-HPA-5b-induced neonatal alloimmune thrombocytopenia: antibody titre as a
      predictor. Collaborative Study Group.
AB  - Anti-HPA-5b is the most commonly found platelet-specific antibody among pregnant
      women, but it does not cause severe fetal-neonatal alloimmune thrombocytopenia in
      the majority of affected infants. However, as the sequelae of the affected
      children may become severe, it is necessary to identify the risk factors for
      neonatal alloimmune thrombocytopenia. Of 21 354 consecutive pregnant women, 138
      [0.65%; 95% confidence interval (CI) 0.54-0.75%], corresponding to 13.2% of the
      1049 HPA-5b- women calculated by the gene frequency, were positive for anti-HPA
      5b at the first trimester. Anti-HPA-5b was titrated in specimens obtained at the
      third trimester and antibody-positive women and their neonates were HPA-5
      genotyped. Platelet counts in cord blood and 3 d after birth were assessed in the
      infants born to these mothers. Chi-square analysis showed no significant
      relationship between the titres of maternal antibody to HPA-5b and the number of
      pregnancies. There was a significant difference in platelet counts at d 3 between
      neonates who were compatible (267 x 109/l) or incompatible (220 x 109/l, P <
      0.05) with maternal anti-HPA-5b. HPA-5b antibody titres >/= 64 were related to
      the development of thrombocytopenia (< 150 x 109/l) in neonates 1 d and 3 d after
      birth. A high titre (>/= 64) had a positive predictive value of 50% for
      thrombocytopenia 3 d after birth when the infant was HPA-5b+ and a negative
      predictive value of 100%. These results indicate that a high titre (>/= 64) of
      anti-HPA-5b is associated with a higher risk of neonatal thrombocytopenia, even
      if anti-HPA-5b-induced severe thrombocytopenia rarely develops.

PMID- 10931002
TI  - Treatment of chronic myelomonocytic leukaemia by allogeneic marrow
      transplantation.
AB  - We evaluated the outcome of allogeneic bone marrow transplantation (BMT) in 21
      patients with chronic myelomonocytic leukaemia (CMML) who were treated at the
      Fred Hutchinson Cancer Research Center between 1990 and 1998. There were 11 male
      and 10 female patients with a median age of 47.4 years (range 1.0-62.9). Patients
      were conditioned either with total body irradiation (TBI) and chemotherapy, with
      or without antithymocyte globulin (n = 19), or with chemotherapy alone (n = 2).
      The marrow donor was an HLA-identical sibling in 12 patients, an HLA-non
      identical related donor in three patients and an unrelated volunteer donor in six
      patients. All evaluable patients achieved sustained engraftment. Fifteen patients
      developed grades II-IV acute graft-versus-host disease (GVHD). Nine patients
      (43.0%) are surviving disease free at 0.7-8.1 years (median 6.9) after
      transplantation. Five patients relapsed 75-660 d after transplant and all died.
      Five patients died with organ failure and two died with GVHD and associated
      infections. The Kaplan-Meier estimates of disease-free survival and relapse at 3
      years were 39% and 25% respectively. The probability of survival was improved in
      patients with shorter disease duration compared with those with a long interval
      from diagnosis to BMT. Thus, as with other myeloproliferative diseases or
      myelodysplastic syndromes, BMT offers curative therapy for a proportion of
      patients with CMML. We suggest that patients with CMML who have a suitable donor
      should be considered for transplantation, probably early in their disease course.
      However, it will be important to develop new regimens with enhanced antileukaemic
      efficacy without further increasing regimen-related toxicity and mortality.

PMID- 10931004
TI  - Transfusion-associated graft vs. host disease in a patient with high-grade B-cell
      lymphoma. Should cellular products for patients with non-Hodgkin's lymphoma be
      irradiated?
AB  - We present the case of a 64-year-old man who died from transfusion-associated
      graft vs. host disease (TA-GVHD) having been treated 2 years earlier for a high
      grade, non-Hodgkin's lymphoma (NHL). We suggest that he was at increased risk of
      developing TA-GVHD as a result of the NHL and its subsequent treatment, and
      propose that patients with NHL should be added to those 'at risk' groups who
      receive irradiated cellular blood components.

PMID- 10931005
TI  - Severe pancytopenia triggered by recombinant hepatitis B vaccine.
AB  - We describe the case of a teenager who developed fever, arthritis, cutaneous
      vasculitis and severe pancytopenia 3 weeks after the third vaccination boost with
      a recombinant hepatitis B vaccine. Bone marrow examination showed paucity of late
      myeloid elements and, subsequently, maturation arrest. Interferon-gamma (IFN
      gamma) production by peripheral blood mononuclear cells from the patient was
      dramatically increased. An underlying immune predisposition (HLA-DR3) may have
      indirectly enabled the vaccine to trigger a hepatitis B virus-specific cytotoxic
      T-lymphocyte response. It is therefore possible that the pancytopenia was induced
      by a dysregulation of the CD8+ T-cell compartment via increased IFN-gamma
      production.

PMID- 10931006
TI  - Complication of rapidly progressive glomerulonephritis in severe congenital
      neutropenia treated with long-term granulocyte colony-stimulating factor
      (filgrastim).

PMID- 10931007
TI  - Decreased cord blood yield in post-term pregnancy: a comparative study.

PMID- 10931008
TI  - Polycythaemia as a complication of transdermal testosterone therapy.

PMID- 10931009
TI  - TEL and MN1 fusion in myelodysplastic syndrome: new evidence for a therapy
      related event.

PMID- 10931010
TI  - SYNDECAN-1 (CD138) expression in human non-Hodgkin's lymphomas.

PMID- 10931011
TI  - Controversies surrounding the clonogenic origin of multiple myeloma.

PMID- 10931012
TI  - Translocation t(6;14)(p12;q32): a novel cytogenetic abnormality in splenic
      lymphoma with villous lymphocytes.

PMID- 10931013
TI  - The effect of litigation on surgical practice in the USA.

PMID- 10931015
TI  - COPE: committee on publication ethics

PMID- 10931014
TI  - The 'foreign' author.

PMID- 10931016
TI  - A problem bile duct stone.

PMID- 10931017
TI  - Molecular technology and pancreatic cancer.
AB  - BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer death in the
      Western world. Despite improvement in operative mortality rates, little impact
      has been made on overall 5-year survival. This review discusses the molecular
      changes peculiar to pancreatic cancer and how the use of molecular technology
      might affect detection, screening, diagnosis and treatment of the disease.
      METHODS: A literature review was performed using the National Library of
      Medicine's Pubmed database; this was combined with ongoing work within the Queen
      Elizabeth Hospital, Birmingham. RESULTS: Over the past 20 years great strides
      have been made in our understanding of the molecular basis of disease. Advances
      in molecular biology are now reshaping how diseases are screened for, diagnosed,
      investigated and treated. In recent years collaboration between clinicians and
      basic scientists has revealed a unique pattern of genetic and molecular events in
      pancreatic cancer. This review discusses how these advances may impact on
      patients with this disease. CONCLUSION: The past decade has seen some improvement
      in outlook for patients with pancreatic cancer, but the 'molecular age' promises
      to deliver even better results.

PMID- 10931018
TI  - Mesh compared with non-mesh methods of open groin hernia repair: systematic
      review of randomized controlled trials.
AB  - BACKGROUND: Open tension-free methods of groin hernia repair have been widely
      adopted despite little rigorous evaluation. METHODS: Information was assimilated
      from all randomized or quasi-randomized trials comparing open mesh with open non
      mesh methods to assess benefits and safety. Electronic databases were searched
      and members of the EU Hernia Trialists Collaboration consulted to identify
      trials. Prespecified data items were extracted from reports, and quantitative or,
      if not possible, qualitative meta-analysis was performed. RESULTS: Fifteen
      eligible trials, which included 4005 participants, were identified. There were
      similar numbers of complications in each group, with few data to address short
      term pain and length of stay in hospital. Return to usual activities was quicker
      in the mesh group for seven of ten trials (P not significant). There were fewer
      reported recurrences in the mesh groups: overall 21 (1.4 per cent) of 1513 versus
      72 (4.4 per cent) of 1634 (odds ratio 0.39 (95 per cent confidence interval 0.25
      0. 59); P < 0.001). CONCLUSION: Although the rigorous search maximized trial
      identification, formal meta-analysis was limited by the variation in trial
      reporting. Within the data available, mesh repair was associated with fewer
      recurrences.

PMID- 10931019
TI  - Laparoscopic compared with open methods of groin hernia repair: systematic review
      of randomized controlled trials.
AB  - BACKGROUND: The place of laparoscopic groin hernia repair remains controversial.
      Individual randomized controlled trials alone have not provided statistically
      reliable results when considering recurrence, potentially serious complications
      and chronic pain. METHODS: A rigorous systematic review was performed of
      published data from all relevant randomized or quasi-randomized trials.
      Electronic databases were searched and members of the EU Hernia Trialists
      Collaboration consulted to identify trials. Prespecified data items were
      extracted from reports and, where possible, quantitative meta-analysis was
      performed. RESULTS: Thirty-four published reports of eligible trials were
      included, involving 6804 participants. Sample sizes ranged from 20 to 1051, with
      follow-up from 6 weeks to 36 months. Duration of operation was longer in the
      laparoscopic groups (P < 0.001, Sign test). Operative complications were uncommon
      for both methods, but visceral and vascular injuries were more frequent in the
      laparoscopic group (4.7 per 1000 versus 1. 1 per 1000). Postoperative pain was
      less among laparoscopic groups (P = 0.08). Length of hospital stay did not differ
      significantly between groups (P = 0.50), but return to usual activity was earlier
      for laparoscopic groups (P < 0.001). Chronic pain and numbness were reported for
      only a small minority of trials. Overall, recurrences did not differ between
      groups, but comparison of laparoscopic with open non-mesh repair favoured
      laparoscopic methods, significantly so for transabdominal preperitoneal repair
      (Peto odds ratio 0.56 (95 per cent confidence interval 0.33-0.93); P = 0.026).
      CONCLUSION: Although the rigorous search maximized trial identification,
      variation in trial reporting made formal meta-analysis difficult. Laparoscopic
      repair was associated with less postoperative pain and more rapid return to
      normal activities, but it takes longer to perform and may increase the risk of
      rare, but serious, complications.

PMID- 10931020
TI  - Randomized clinical trial of micronized flavonoids in the early control of
      bleeding from acute internal haemorrhoids.
AB  - BACKGROUND: Patients with acute bleeding from internal haemorrhoids often have to
      be referred by the general practitioner to the surgeon for definitive treatment
      with invasive outpatient procedures. At the initial consultation, patients
      frequently seek postponement of immediate surgery to a more convenient time.
      Effective and rapid non-invasive control of acute bleeding could be of practical
      use in scheduling surgery to a time convenient to both patient and surgeon.
      METHODS: In a 90-day randomized, double-blind study treatment with a micronized
      purified flavonoid fraction (MPFF) was compared with placebo, in 100 outpatients
      who presented for treatment of acute internal haemorrhoids of less than 3 days'
      duration. The primary endpoint was cessation of bleeding on the third day of
      treatment. RESULTS: Of 50 patients randomized to each group, acute bleeding
      ceased by the third day in 40 (80 per cent) who received MPFF compared with 19
      (38 per cent) who had placebo (P < 0.01). Mean(s.d. ) duration of acute bleeding
      from onset to cessation of 4.9(1.6) days was 2.1 (95 per cent confidence interval
      1.2-2.9) days less than that in patients receiving placebo (P < 0.01). Continued
      treatment in patients with no bleeding prevented a relapse in 30 of 47 patients,
      compared with 12 of 30 receiving placebo (P < 0.05). CONCLUSION: Patients with
      acute internal haemorrhoids treated with MPFF had rapid cessation of bleeding and
      a reduced risk of relapse. This could be of value in the more convenient timing
      of treatment with invasive outpatient procedures.

PMID- 10931021
TI  - Randomized clinical trial of laparoscopic versus open fundoplication: blind
      evaluation of recovery and discharge period.
AB  - BACKGROUND: There is a widespread belief that introduction of the laparoscopic
      technique in antireflux surgery has led to easier postoperative recovery. To test
      this hypothesis a prospective randomized clinical trial with blind evaluation was
      conducted between laparoscopic and open fundoplication. METHODS: Sixty patients
      with gastro-oesophageal reflux disease were randomized to open or laparoscopic
      360 degrees fundoplication. The type of operation was unknown to the patient and
      the evaluating nurses after operation. RESULTS: The operating time was longer in
      the laparoscopy group, median 148 versus 109 min (P < 0.0001). The need for
      analgesics was less in the laparoscopically operated patients, 33.9 versus 67.5
      mg morphine per total hospital stay (P < 0.001). There was no significant
      difference in postoperative nausea and vomiting. On the first day after operation
      patients in the laparoscopy group had better respiratory function: forced vital
      capacity 3.2 versus 2. 2 litres (P = 0.004) and forced expiratory volume 2.6
      versus 2.0 litres (P = 0.008). Postoperative hospital stay was shorter in the
      laparoscopic group, median (range) 3 (2-6) versus 3 (2-10) days (P = 0.021). No
      difference was found in the duration of sick leave. CONCLUSION: Laparoscopic
      fundoplication was associated with a longer operating time, better respiratory
      function, less need for analgesics and a shorter hospital stay, while no
      reduction in the duration of postoperative sick leave was found compared with
      open surgery.

PMID- 10931022
TI  - Preoperative portal vein embolization improves prognosis after right hepatectomy
      for hepatocellular carcinoma in patients with impaired hepatic function.
AB  - BACKGROUND: Percutaneous transhepatic portal vein embolization (PTPE) increases
      the safety of subsequent major hepatectomy. The aim of this study was to
      determine the effect of PTPE on long-term prognosis after hepatectomy in patients
      with hepatocellular carcinoma (HCC). METHODS: Seventy-one patients with HCC
      underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was
      performed in 33 patients (group 1) and was not used in 38 patients (group 2).
      Outcome after operation was compared between the groups. The patients were
      further divided according to the median tumour diameter (cut-off 6 cm) and
      indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent).
      RESULTS: The cumulative survival rate was significantly higher in group 1 than in
      group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival
      rates were similar in both groups. Of patients with tumour recurrence after right
      hepatectomy, those in group 1 were more frequently subjected to further
      treatment. CONCLUSION: Preoperative PTPE improves the prognosis after right
      hepatectomy for HCC in patients with impaired hepatic function, although it does
      not prevent tumour recurrence.

PMID- 10931023
TI  - Pancreatic fistula after pancreatic head resection.
AB  - BACKGROUND: Pancreatic resections can be performed with great safety. However,
      the morbidity rate is reported to be 40-60 per cent with a high prevalence of
      pancreatic complications. The aim of this study was to analyse complications
      after pancreatic head resection, with particular attention to morbidity and
      pancreatic fistula. METHODS: From November 1993 to May 1999, perioperative and
      postoperative data from 331 consecutive patients undergoing pancreatic head
      resection were recorded prospectively. Data were analysed and grouped according
      to the procedure performed: classic Whipple resection, pylorus-preserving
      pancreatoduodenectomy (PPPD) or duodenum-preserving pancreatic head resection
      (DPPHR). RESULTS: Pancreatic head resection had a mortality rate of 2.1 per cent;
      the difference in mortality rate between the three groups (0.9-3.0 per cent) was
      not significant. Total and local morbidity rates were 38.4 and 28 per cent
      respectively. DPPHR had a lower morbidity, both local and systemic, than
      pancreatoduodenectomy. The prevalence of pancreatic fistula was 2.1 per cent in
      331 patients, and was not dependent on the procedure or the aetiology of the
      disease. Reoperations were performed in 3.9 per cent of patients, predominantly
      for bleeding and non-pancreatic fistula. None of the patients with pancreatic
      fistula required reoperation or died in the postoperative course. CONCLUSION: A
      standardized technique and a continuing effort to improve perioperative
      management may be responsible for low mortality and surgical morbidity rates
      after pancreatic head resection. Pancreatic complications occur with Whipple,
      PPPD and DPPHR procedures with a similar prevalence. Pancreatic fistula no longer
      seems to be a major problem after pancreatic head resection and rarely
      necessitates surgical treatment.

PMID- 10931024
TI  - Changing referral pattern of biliary injuries sustained during laparoscopic
      cholecystectomy.
AB  - SUMMARY: More patients with less severe type biliary injury are being referred
      earlier to a specialist hepatobiliary unit. Most patients still have ineffective
      corrective surgery before transfer. Presented in part to the European Congress of
      the International Hepato-Pancreatico-Biliary Association in Budapest, Hungary,
      May 1999 and published in abstract form as Digestive Surgery 1999; 16(Suppl 1):
      32.

PMID- 10931025
TI  - Prognosis and surgical management of patients with palpable inguinal lymph node
      metastases from melanoma.
AB  - BACKGROUND: The appropriate management of melanoma metastatic to inguinal lymph
      nodes remains controversial. The aim of this study was to identify disease- and
      treatment-related factors that influence the outcome of patients undergoing
      therapeutic groin dissection for clinically detectable melanoma lymph node
      metastases. METHODS: A retrospective analysis was performed on data collected
      from the case records of patients who had a therapeutic inguinal lymph node
      dissection performed between 1984 and 1998. RESULTS: Some 132 patients were
      suitable for inclusion. Sixty patients had superficial inguinal lymph node
      dissection (SLND) and 72 had combined superficial inguinal and pelvic lymph node
      dissection (CLND). There was no difference in postoperative morbidity or major
      lymphoedema between SLND and CLND. The overall survival rate was 34 per cent at 5
      years. On univariate analysis, age (P = 0.003), the number of involved
      superficial lymph nodes (P = 0.001) and the presence of extracapsular spread (P =
      0.003) were found to have a significant impact on survival. The presence or
      absence of pelvic lymph node metastases in patients who had CLND was a
      significant prognostic factor for survival (5-year survival 19 versus 47 per
      cent; P = 0.015). CONCLUSION: The prognosis of patients with clinically
      detectable melanoma metastases to the groin is variable and related to the
      biological characteristics of each case. CLND provided additional prognostic
      information and optimal regional control with no increased morbidity compared
      with SLND.

PMID- 10931026
TI  - Experimental study of faecal continence and colostomy irrigation.
AB  - BACKGROUND: Colostomy irrigation is a useful method of achieving faecal
      continence in selected conditions, but remains largely underutilized because it
      is time consuming. This study investigated the effect of modifying irrigation
      technique (route, infusion regimen and pharmacological manipulation) on colonic
      emptying time in a porcine model. METHODS: An end-colostomy and caecostomy were
      fashioned in six pigs. Twenty markers were introduced into the caecum immediately
      before colonic irrigation. Irrigation route (antegrade or retrograde), infusion
      regimen (tap water, polyethylene glycol (PEG), 1.5 per cent glycine) and
      pharmacological agent (glyceryl trinitrate (GTN) 0.25 mg/kg, diltiazem 3.9 mg/kg,
      bisacodyl 0.25 mg/kg) were assigned to each animal at random. Colonic transit was
      assessed by quantifying cumulative expelled markers (CEM) and stool every hour
      for 12 h. RESULTS: Mean CEM at 6 h for bisacodyl, GTN and diltiazem were 18.17,
      12.17 and zero respectively; all pairwise differences in means were significant
      (P < 0.001). The difference at 12 h between the two routes (P = 0.001) and three
      fluids (tap water 6.75, glycine 14.83, PEG 16.33; P < 0. 001) was significant,
      but not for PEG versus glycine and bisacodyl versus GTN. Cumulative output was
      significantly more with the antegrade than retrograde route using PEG, but the
      difference in mean cumulative output for bisacodyl and GTN at 12 h was not
      significant. CONCLUSION: Colonic emptying is more efficient with antegrade than
      retrograde irrigation. PEG and glycine enhance emptying similar to bisacodyl and
      GTN solution. These findings show promise for improved faecal continence by
      colostomy irrigation and may justify construction of a Malone conduit at the time
      of colostomy in selected patients who wish to irrigate. Presented in part to the
      British Society of Gastroenterology in Glasgow, UK, March 1999, and published in
      abstract form as Gut 1999; 44(Suppl 1): A135

PMID- 10931028
TI  - In-hospital delay in the diagnosis of breast cancer.
AB  - BACKGROUND: There is evidence that delay in the diagnosis of breast cancer may
      prejudice survival. The aim of this study was to determine the incidence, time
      trends and causes of delay in a dedicated breast clinic. METHODS: The interval
      between first breast clinic visit and a definitive diagnosis was recorded in all
      patients with invasive breast cancer between 1988 and 1997. In all patients with
      a delay of 3 months or more, the case notes were reviewed for evidence of a
      triple assessment (clinical examination, imaging and needle biopsy). The
      principal cause of delay was identified. RESULTS: Of 1004 patients with invasive
      breast cancer, there was a delay in diagnosis of 3 months or more in 42 patients
      between 1988 and 1997, an incidence of 4.2 per cent. The median delay was 6
      months and the median age at diagnosis was 53 (range 27-89) years. Triple
      assessment was undertaken in 30 patients; ten did not have a needle biopsy
      performed and three patients had no mammography. The principal cause of delay
      was: false-negative or inadequate fine-needle aspiration cytology (FNAC) in 19
      patients, failure of follow-up in eight, clinical signs did not impress in five,
      FNAC not carried out in four, false-negative mammogram in three, failure of
      needle localization in two and one patient did not accept clinical advice. The
      annual incidence of delay in diagnosis did not change significantly over the 10
      year interval. CONCLUSION: Triple assessment is not sufficiently sensitive to
      detect every breast cancer and a small incidence of diagnostic delay is therefore
      inevitable with current techniques.

PMID- 10931027
TI  - Morbidity and functional outcome after double dynamic graciloplasty for anorectal
      reconstruction.
AB  - BACKGROUND: After abdominoperineal resection (APR), anorectal reconstruction with
      dynamic graciloplasty has been proposed to avoid abdominal colostomy and improve
      quality of life. Graciloplasties involving one or two gracilis muscles with
      various configurations have been described. The aim of this study was to evaluate
      morbidity and functional results in a homogeneous series of patients undergoing
      double dynamic graciloplasty following APR for rectal cancer. PATIENTS AND
      METHODS: : From May 1995 to May 1998, 15 patients (ten men and five women; mean
      age 54 (range 39-77) years) underwent anorectal reconstruction with double
      dynamic graciloplasty after APR for low rectal carcinoma. All patients had
      preoperative radiotherapy (45 Gy), 11 with concomitant chemotherapy, eight had
      intraoperative radiotherapy (15 Gy) and ten received adjuvant chemotherapy for 6
      months. The surgical procedure was performed in three stages: APR with
      coloperineal anastomosis and double graciloplasty (double muscle wrap);
      implantation of the stimulator 2 months later; and ileostomy closure after a
      training period. RESULTS: There was no operative death. At a mean of 28 (range 3
      48) months of follow-up, there was no local recurrence; two patients had lung
      metastases. Early and late morbidity occurred in 11 patients, mainly related to
      the neosphincter (12 of 16 complications). The main complication was stenosis of
      the neosphincter (n = 6), which developed with electrical stimulation. Of 12
      patients available for functional outcome, seven were continent, two were
      incontinent and three had an abdominal colostomy (two for incontinence, one for
      sepsis). Compared with patients without stenosis, patients with neosphincter
      stenosis required major reoperations (four versus zero) and had a poor outcome
      (two of six versus five of six with a good result). CONCLUSION: The double
      dynamic graciloplasty is associated with a high risk of neosphincter stenosis,
      which may entail morbidity, reintervention and poor functional results. The
      stenosis is a heterogeneous feature of the neosphincter induced by asymmetrical
      traction of both gracilis muscles. It is suggested that single dynamic
      graciloplasty should be used for anorectal reconstruction after APR. Presented to
      the 101st congress of the Association Francaise de Chirurgie in Paris, France,
      October 1999, and to the European Council of Coloproctology in Munich, Germany,
      October-November 1999

PMID- 10931029
TI  - Clinical relevance of sentinel lymph nodes outside the axilla in patients with
      breast cancer.
AB  - BACKGROUND: Lymphatic mapping in patients with breast cancer can reveal sentinel
      lymph nodes that are not located at level I-II of the axilla. Little is known
      about the clinical relevance of these nodes. METHODS: Some 113 consecutive
      patients with clinical stage T1-3 N0 M0 breast cancer were studied. Based on
      preoperative lymphoscintigraphy, sentinel node biopsy was performed guided by a
      gamma probe and patent blue dye. All sentinel nodes that were visible on
      lymphoscintigraphy were sought. Pathological examination of the sentinel nodes
      included step-sections and staining with CAM 5. 2. Axillary node dissection was
      performed regardless of sentinel lymph node status. RESULTS: Twenty-one (19 per
      cent) of 113 patients had sentinel lymph nodes outside level I-II of the axilla,
      mostly in the internal mammary chain. Twenty-two of the 30 sentinel nodes at
      these sites were harvested. Three patients had sentinel nodes only outside the
      axilla. Four other patients had metastases outside the axilla. This changed
      postoperative treatment in three patients. No postoperative complication
      occurred. CONCLUSION: Sentinel lymph nodes outside level I-II of the axilla were
      present in 19 per cent of patients with breast cancer in this series. Biopsy of
      these nodes was technically demanding but was performed without additional
      morbidity. The clinical impact was limited; treatment changed in only 3 per cent.
      Presented to the 52nd annual meeting of the Society of Surgical Oncology in
      Orlando, Florida, USA, March 1999 and the First International Congress on the
      Sentinel Node in Diagnosis and Treatment of Cancer in Amsterdam, The Netherlands,
      April 1999, and published in abstract form as Eur J Nucl Med 1999; 26(Suppl): S71

PMID- 10931031
TI  - Specialized intestinal metaplasia in patients with gastro-oesophageal reflux
      disease.

PMID- 10931030
TI  - Transvenous sclerotherapy for huge oesophagogastric varices using open injection
      sclerotherapy.
AB  - BACKGROUND: The optimum procedure for long-term management of oesophagogastric
      varices when endoscopic sclerotherapy or ligation fails is yet to be established.
      This report describes a new procedure for treating huge oesophagogastric varices
      by open injection sclerotherapy. METHODS: Twenty-three patients with huge
      oesophagogastric varices underwent laparotomy and devascularization of the upper
      stomach with splenectomy. The left gastric vein was catheterized for repeated
      injection of 5 per cent ethanolamine oleate during the postoperative period.
      RESULTS: In all patients, the varices were eradicated after a mean of 3 sessions
      of sclerotherapy. There were no deaths or major complications during the mean
      follow-up period of 41 months. Small recurring varices in two patients were
      treated successfully by endoscopic sclerotherapy and interventional radiology.
      CONCLUSION: Open injection sclerotherapy is an effective and safe procedure for
      the treatment of huge oesophagogastric varices.

PMID- 10931032
TI  - Management of the axilla in operable breast cancer treated by breast
      conservation: a randomized clinical trial.

PMID- 10931033
TI  - Management of the axilla in operable breast cancer treated by breast
      conservation: a randomized clinical trial.

PMID- 10931034
TI  - CORRESPONDENCE: Author's reply

PMID- 10931035
TI  - Randomized clinical trial of haemorrhoidectomy under a mixture of local
      anaesthesia versus general anaesthesia.

PMID- 10931036
TI  - Randomized clinical trial of topical phenylephrine in the treatment of faecal
      incontinence.

PMID- 10931038
TI  - The final product.

PMID- 10931037
TI  - Litigation and surgical practice in the UK.

PMID- 10931039
TI  - Soft tissue sarcoma involving the sciatic nerve.

PMID- 10931040
TI  - Portal flow augmentation for liver cirrhosis.
AB  - BACKGROUND: Portal hypertension due to chronic liver disease is a major cause of
      death worldwide. Orthotopic liver transplantation offers the best therapeutic
      option but is available to only a minority of patients. In the past few years
      mechanically pumping portal venous inflow has been reported to reduce portal
      hypertension and improve liver function. METHODS: A review of the published data
      on augmented portal perfusion for the treatment of portal hypertension in
      cirrhosis was carried out by searching Medline and other online databases. From
      each published study portal pressure and blood flow data before and after
      augmented portal perfusion were used to calculate the change in mean intrahepatic
      portal vascular resistance (IHPR). The standardized data were then combined to
      allow meta-analysis. RESULTS: Seven papers were identified on normal and
      cirrhotic animal and human livers with augmented flow (50% to fourfold over
      baseline) for 30-180 min. Meta-analysis revealed that the increased portal venous
      inflow was associated with a significant rise in portal venous pressure on the
      hepatic side (P < 0.001), a significant reduction on the mesenteric side (P <
      0.001) and a significant reduction in IHPR (P = 0.013). Limited data were
      available to support improved liver function. CONCLUSION: Detailed in vivo
      cirrhotic liver studies on augmented portal flow in experimental models assessing
      haemodynamic and functional changes are required before clinical evaluation.

PMID- 10931041
TI  - E-cadherin-catenin cell-cell adhesion complex and human cancer.
AB  - BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial
      cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in
      the expression or function of this complex results in loss of intercellular
      adhesion, with possible consequent cell transformation and tumour progression.
      Recently, much progress has been made in understanding the interaction between
      the different components of this protein complex and how this cell-cell adhesion
      complex is modulated in cancer cells. METHODS: This is an update of the role of
      the E-cadherin-catenin complex in human cancers. It emphasizes new features and
      the possible role of the complex in clinical practice, discussed in the light of
      165 references obtained from the Medline database from 1995 to 1999. RESULTS:
      More evidence is now appearing to suggest that disturbance in protein-protein
      interaction in the E-cadherin-catenin adhesion complex is one of the main events
      in the early and late steps of cancer development. An inverse correlation is
      found between expression of the E-cadherin-catenin complex and the invasive
      behaviour of tumour cells. Therefore, E-cadherin-catenin may become a significant
      prognostic marker for tumour behaviour. Besides its role in establishing tight
      cell-cell adhesion, beta- catenin plays a major role in cell signalling and
      promotion of neoplastic growth. This suggests its dual role as a tumour
      suppressor and as an oncogene in human cancers. CONCLUSION: Recent developments
      show that the E-cadherin-catenin complex is more than a 'sticky molecular
      complex'. Further studies may yield greater insight into the early molecular
      interactions critical to the initiation and progression of tumours. This should
      aid the development of novel strategies for both prevention and treatment of
      cancer.

PMID- 10931043
TI  - DIGEST: digest

PMID- 10931042
TI  - Hyperthermic intraperitoneal chemoperfusion in the treatment of locally advanced
      intra-abdominal cancer.
AB  - BACKGROUND: Surgical treatment of intra-abdominal cancer is often followed by
      local recurrence. In a subgroup of patients, local recurrence is the sole site of
      disease, reflecting biologically low-grade malignancy. These patients might,
      therefore, benefit from local treatment. Recently, debulking surgery followed by
      hyperthermic chemoperfusion has been proposed in the treatment of locally
      advanced or recurrent intra-abdominal cancer. This paper reviews the rationale
      and assesses the currently accepted indications for and results of this novel
      treatment. METHODS: A systematic web-based literature review was performed.
      Information was also retrieved from handbooks, congress abstracts and ongoing
      clinical trials. RESULTS: A growing body of experimental evidence supports the
      use of hyperthermia combined with chemotherapy as an adjunct to cytoreductive
      surgery. Randomized clinical trials are available to support its use in the
      treatment and prevention of peritoneal carcinomatosis following resection of
      pathological tumour stage pT3 or pT4 gastric cancer; several other phase III
      trials are ongoing. Numerous phase I and II trials have reported good results for
      various other indications, with acceptable morbidity and mortality rates. Case
      mix, limited patient numbers and absence of a standardized technique are,
      however, a drawback in many of these series. CONCLUSION: For a subgroup of
      patients with peritoneal cancer without distant disease, debulking surgery
      followed by hyperthermic chemoperfusion may offer a chance of cure or palliation
      in this otherwise untreatable condition. This novel therapy should, however, be
      considered experimental until further results from ongoing phase III trials
      become available.

PMID- 10931044
TI  - Severity of acute pancreatitis: a multivariate analysis of oxidative stress
      markers and modified Glasgow criteria.
AB  - BACKGROUND: It is unknown whether measurement of markers of oxidative stress can
      improve the prediction of severity of acute pancreatitis. METHODS: Consecutive
      patients admitted with a diagnosis of acute pancreatitis were divided into mild
      (n = 62) and severe (n = 23) groups based on the Atlanta classification. Plasma
      oxidative stress markers were measured within 24 h of admission and included
      ascorbic acid (endogenous antioxidant), protein carbonyl (a marker of protein
      oxidation), thiobarbituric acid reactive substances (a marker of lipid
      peroxidation) and myeloperoxidase (a neutrophil enzyme that produces oxidants).
      Canonical correlation analysis was used to describe the relationship between
      these markers and the modified Glasgow criteria. Canonical variate analysis was
      used to define the best variables that could discriminate mild and severe
      pancreatitis. RESULTS: There was a significant correlation between markers of
      oxidative stress and the modified Glasgow criteria (first canonical correlation
      0.69, P < 0.0001, Wilk's lambda test). Blood urea, serum albumin and white cell
      count were the best variables that discriminated mild and severe acute
      pancreatitis, and all were better than the oxidative stress markers. CONCLUSION:
      The markers of oxidative stress were highly correlated with the severity of
      pancreatitis. They are unlikely to be better than the modified Glasgow criteria
      in predicting it.

PMID- 10931045
TI  - In vivo evaluation of an implantable portal pump system for augmenting liver
      perfusion.
AB  - BACKGROUND: Increasing portal inflow in cirrhosis using a mechanical pump reduces
      portal venous pressure and improves liver function. A pump has been developed for
      portal vein implantation in human cirrhosis. This study describes the initial in
      vivo evaluation in a porcine model. METHODS: Five Large White pigs underwent
      laparotomy and exposure of the liver. Flow in the hepatic artery, portal vein and
      hepatic microcirculation was monitored continuously. Hepatic tissue oxygenation
      was measured by near-infrared spectroscopy. After baseline measurements the pump
      was inserted into the portal vein. Pump flow rate was then increased stepwise to
      50 per cent over the baseline value for a period of 2 h. The pump was then
      stopped for 20 min and left in situ while continuing to collect systemic and
      hepatic haemodynamic data. The animal was killed and biopsies for histological
      examination were taken from the liver, small intestine and spleen. RESULTS: The
      baseline total hepatic blood flow was 626(39) ml/min; the hepatic artery supplied
      18.4(2.1) per cent and the portal vein 81.6(2.1) per cent. The pump was inserted
      successfully in all animals without surgical complications. During surgical
      insertion of the pump, the temporary portal vein occlusion resulted in a
      significant rise in hepatic artery blood flow (22(3) per cent; P < 0.01 versus
      baseline). Portal vein flow was augmented by pumping; there was a significant
      correlation between the pump motor speed and portal vein flow (P < 0.0001). This
      inflow correlated directly with flow in the hepatic microcirculation and hepatic
      tissue oxygenation (P < 0.001). The pump ran satisfactorily throughout the study.
      Histological examination revealed no evidence of structural damage to the liver
      or ischaemic changes in the small intestine or spleen. CONCLUSION: It is
      technically possible and safe to insert an implantable pump in the portal vein.
      Portal venous blood flow can be increased up to 50 per cent with a resultant
      increase in flow in the hepatic microcirculation and hepatic oxygenation and
      without adverse effects on either hepatic or systemic haemodynamics.

PMID- 10931046
TI  - Analysis of 153 gunshot wounds of the liver.
AB  - BACKGROUND: Gunshot wounds of the liver may result in substantial morbidity and
      death, and optimal management of complex injuries is controversial. METHODS: One
      hundred and fifty-three patients with civilian gunshot liver injuries were
      treated during the 10-year period 1986-1995. Demographic, clinical and operative
      data were recorded. Factors influencing postoperative complications and death
      were analysed. RESULTS: One hundred and forty-two patients (93 per cent) had
      single missile injuries and 11 (7 per cent) had shotgun injuries. Three patients
      were treated non-operatively and 150 patients underwent operation. In 105
      patients (70 per cent) the injuries to the liver were minor and required either
      no treatment (93) or simple suture of bleeding vessels (12). Forty-five patients
      (30 per cent) had major injuries which were either packed only (26) or required
      more complex surgical intervention (19). This included resectional debridement
      (ten), major venous repair (eight) and hepatotomy (one); eight of these patients
      required packing combined with the procedure. Associated intra-abdominal injuries
      occurred in 115 patients (77 per cent). The overall mortality rate was 17 per
      cent (26 patients). Death was directly attributable to the liver injury in 13
      patients (8 per cent), 12 of whom died from uncontrolled bleeding. Complications
      occurred in 63 (51 per cent) of 124 survivors, and correlated with the type and
      severity of the liver injury and the number of associated injuries. CONCLUSION:
      Most gunshot liver injuries can be managed by simple surgical techniques. In
      complex injuries control of major haemorrhage is vital and perihepatic packing
      may be life saving before undertaking definitive repair of the injury under
      controlled conditions.

PMID- 10931047
TI  - Expression and processing of gastrin in pancreatic adenocarcinoma.
AB  - BACKGROUND: Gastrin is a trophic hormone and promotes growth of gastrointestinal
      and non-gastrointestinal cancers. Studies both in vitro and in vivo have
      suggested that pancreatic cancer cells not only have the ability to respond to
      circulating forms of gastrin but also to respond to the autocrine production of
      gastrin and its precursors. The aim of this study was to identify the expression
      of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated
      gastrin in both normal pancreas and pancreatic adenocarcinoma. METHODS: Tissue
      sections from patients with normal pancreas (n = 10) and pancreatic cancer (n =
      22) were assessed using immunohistochemical methods for CCK-B/gastrin receptor,
      progastrin, glycine-extended gastrin and amidated gastrin expression. RESULTS:
      Normal pancreas showed no expression of receptor or gastrin isoforms except for
      occasional cells in the islets. Definite expression of CCK-B/gastrin receptor,
      progastrin, glycine-extended gastrin and amidated gastrin was observed in 95, 91,
      55 and 23 per cent of sections from patients with pancreatic cancer respectively.
      CONCLUSION: Pancreatic cancer cells express CCK-B/gastrin receptor and gastrin
      precursor forms in most patients. Expression of the gastrin precursor forms is
      probably related to autocrine production. New therapeutic strategies need to be
      developed for the management of pancreatic cancer. Targeting gastrin and its
      receptor may provide a novel treatment option.

PMID- 10931048
TI  - Diagnosis and management of cystic pancreatic tumours with mucin production.
AB  - BACKGROUND: To aid selection of the most appropriate treatment for intraductal
      tumours (IDTs) and mucinous cystic tumours (MCTs) of the pancreas, this study
      describes the clinical and diagnostic features of these tumours and compares the
      clinicodiagnostic features of malignant and benign tumours and hyperplasia.
      METHODS: The clinical features of 28 IDTs (four cases of hyperplasia, six
      adenomas and 18 adenocarcinomas) and six MCTs (four adenomas and two
      adenocarcinomas) were studied. RESULTS: An IDT was found in 24 men and four women
      with a mean age of 64.5 years, whereas all patients with an MCT were women, with
      a mean age of 50.8 years. Twenty IDTs were located in the pancreatic head,
      whereas all MCTs were in the pancreatic body-tail. The mean size of IDTs was
      smaller than that of MCTs (4.4 versus 7.7 cm). The mean size of hyperplastic
      lesions, adenomas and adenocarcinomas in IDTs were 1.7, 2.9 and 5.4 cm
      respectively. Hyperplastic IDT lesions were smaller than 2 cm without either
      mural nodules or dilatation of the main pancreatic duct. IDTs larger than 3 cm
      with mural nodules and mucin secretion from an enlarged papilla orifice and
      dilatation of the main pancreatic duct were often adenocarcinomas. CONCLUSION:
      Although follow-up of intraductal hyperplasia is a reasonable approach, other
      types of IDT and MCT require surgical treatment.

PMID- 10931049
TI  - Influence of a specialized leg ulcer service on management and outcome.
AB  - BACKGROUND: The organization of leg ulcer care is poorly defined in the
      community. This study assessed the overall influence of a specialized community
      service on management and outcome of chronic leg ulcers, irrespective of
      aetiology. METHODS: Assessment and outcome of ulcers were compared in patient
      samples (n = 200) from East and West Gloucestershire, before and after the
      introduction of specialized clinics into East Gloucestershire. In clinics,
      vascular disease was routinely assessed by duplex scanning and determination of
      the ankle : brachial pressure index. RESULTS: There was no coordinated community
      structure for the care of patients with leg ulcers before the service was
      introduced, and 74 and 67 per cent of limbs in East and West Gloucestershire
      respectively had aetiology undiagnosed. After introduction of the clinics, the 12
      week healing rate increased from 12 to 22 per cent in East Gloucestershire (P =
      0. 05) and to 47 per cent in the specialized East Gloucestershire clinics (P <
      0.001). The 12-month recurrence rate decreased from 50 to 41 per cent in East
      Gloucestershire and to 17 per cent in the East clinics (P < 0.001). The West
      Gloucestershire control showed no significant changes. CONCLUSION: A specialized
      leg ulcer service with defined protocols provides an improved management
      structure for treating patients with leg ulcers in the community. Accurate
      diagnosis of chronic leg ulcers and improved outcome may be achieved within this
      specialized service.

PMID- 10931050
TI  - Effect of contralateral disease on duplex measurements of internal carotid artery
      stenosis.
AB  - BACKGROUND: Duplex ultrasonography is increasingly used as the sole method of
      imaging before carotid endarterectomy. This study investigated the measured
      degree of stenosis in the contralateral carotid artery before and after
      operation. METHODS: Duplex-derived peak systolic velocity (PSV), end-diastolic
      velocity (EDV) and internal carotid artery/common carotid artery (ICA/CCA)
      velocity ratios were measured in the contralateral unoperated ICA before 131
      consecutive unilateral endarterectomies and compared with preoperative
      angiographic findings. Three months later duplex scans were repeated to assess
      whether there had been any alteration in the severity of the stenosis in the
      contralateral unoperated artery. RESULTS: Bilateral ICA disease (greater than 50
      per cent stenosis) was present in 50 patients (38 per cent). Three months after
      operation, ultrasonography of the 105 unoperated, patent, contralateral arteries
      showed a decrease in mean(s.d.) PSV (1.21(0. 83) versus 1.07(0.69) m/s; P < 0.01)
      and EDV (0.41(0.29) versus 0. 35(0.24) m/s; P < 0.01). This resulted in 14 (42
      per cent) of 33 patients with contralateral disease being downgraded to a less
      severe category of stenosis. Use of the ICA/CCA velocity ratio prevented
      overestimation in eight of the 14 patients, while preoperative angiography
      correctly classified 13 of the 14 patients. CONCLUSION: Bilateral carotid artery
      disease can cause overestimation of the severity of stenosis by duplex
      ultrasonography if absolute velocity is used as the main criterion.

PMID- 10931051
TI  - Role of a defunctioning stoma in the management of large bowel Crohn's disease.
AB  - BACKGROUND: The faecal stream plays a significant role in the pathogenesis of
      Crohn's disease. This retrospective study aimed to assess the effect of faecal
      diversion on the natural history of refractory Crohn's colitis (RCC) and severe
      perianal disease (PAD). METHODS: All patients undergoing a defunctioning stoma
      without resection for RCC or PAD between 1970 and 1997 were studied. Indications
      for surgery, acute clinical response, subsequent outcome and stoma rates were
      recorded. RESULTS: Some 73 patients underwent a defunctioning stoma (55 RCC and
      18 PAD). Acute remission was achieved in 63 patients (48 RCC, 15 PAD). Twenty
      nine patients had subsequent closure of the defunctioning stoma (25 of 48 acute
      responders with RCC and four of 15 acute responders with PAD). Eleven patients
      with RCC and two with PAD achieved good long-term function without disease
      relapse (median follow-up 36 months). Overall 52 patients have undergone
      proctocolectomy or remain with a defunctioning stoma (37 with RCC and 15 with
      PAD). CONCLUSION: Faecal diversion is associated with acute clinical remission in
      the majority of patients with RCC and PAD, but sustained benefit occurs less
      often. For selected patients, diversionary surgery alone offers a realistic
      alternative to major bowel resection.

PMID- 10931052
TI  - Bascom's operation in the day-surgical management of symptomatic pilonidal sinus.
AB  - BACKGROUND: Many treatments for symptomatic pilonidal sinus disease have been
      described. Ambulatory treatment with minimal morbidity and a rapid return to
      normal activity is desirable. Bascom's operation fulfils these requirements. This
      paper describes the operative technique and results of treatment. METHODS: Some
      218 patients of mean age 27 years were treated as day cases. The mean duration of
      symptoms was 2.4 years. Sixty-eight per cent of patients had complex disease with
      more than two midline pits and/or a lateral discharging sinus. One hundred and
      eighty-three patients (84 per cent) were operated on under local anaesthesia.
      RESULTS: Ninety-five per cent of patients have been followed up for a mean of
      12.1 (range 1-60) months. All except one midline wound healed. Lateral wounds
      healed after a mean of 4.0 (range 1-15) weeks. Postoperative complications were
      few, including bleeding in 4 per cent and abscess formation treated by reopening
      the lateral incision in 6 per cent. Twenty-one patients (10 per cent) have had
      recurrence and have needed reoperation. CONCLUSION: Bascom's operation is simple
      and results in considerable financial savings with minimal social disruption and
      an early return to work. Recurrent disease is no more frequent than after other
      treatments.

PMID- 10931053
TI  - Compression anastomosis (AKA-2) in colorectal surgery: results in 442 consecutive
      patients.
AB  - BACKGROUND: The morbidity and mortality associated with colorectal surgery
      results partly from anastomotic leakage. Animal experiments have shown some
      advantages of sutureless anastomosis over conventional colorectal anastomosis.
      Compression anastomosis follows the same biological principles as sutureless
      anastomosis. METHODS: The compression anastomosis AKA-2 was evaluated in a
      prospective consecutive audit of 442 patients between September 1989 and August
      1998. RESULTS: Anastomoses were performed in 372 elective and 70 emergency
      situations. The indication for operation was colorectal cancer (56.3 per cent)
      and diverticulitis (23.5 per cent). A defunctioning colostomy was performed in
      110 patients (24.9 per cent). Fourteen patients died (3.2 per cent). Death was
      related to anastomotic complications in three patients (0.7 per cent). Twenty
      four patients (5.4 per cent) developed intra-abdominal complications. There were
      11 symptomatic (2.5 per cent) and six asymptomatic (1.4 per cent) leakages.
      Anastomoses that were more than 10 cm from the anal verge leaked in seven (2.4
      per cent) of 291 cases, while anastomoses between 5 and 10 cm leaked in three
      (2.6 per cent) of 116 cases and those less than 5 cm from the anal verge leaked
      in one (3 per cent) of 35 cases. CONCLUSION: The low incidence of anastomotic
      complications demonstrates good biological healing of compression anastomoses.
      The compression anastomosis AKA-2 is safe in both high and low anterior resection
      and can therefore be recommended for use in colorectal surgery.

PMID- 10931054
TI  - Analysis of risk factors for nosocomial sepsis in surgical patients.
AB  - BACKGROUND: This study aimed to identify patients at high risk for developing
      sepsis following surgery according to criteria determined by the American College
      of Chest Physicians and the Society of Critical Care Medicine Consensus
      Conference on sepsis. METHODS: A prospective case-control study was performed in
      surgical patients in a tertiary care centre over 1 year. Patients were identified
      by a daily prospective surveillance. Controls were selected randomly from the
      daily list of surgical inpatients. Data were collected prospectively. Crude and
      adjusted odds ratios (ORs) and their 95 per cent confidence intervals were
      computed using logistic regression analysis. RESULTS: During follow-up, 99 cases
      and 99 controls were identified. The main risk factors for sepsis found in the
      multivariate analysis were coma within 48 h before sepsis (OR 13.5, 95 per cent
      confidence interval 3.6-50.8), low serum albumin level at admission (OR 15.8, 5.4
      46.4), two or more intrinsic co-morbidities (OR 11.8, 2.8-49.4) and parenteral
      nutrition (OR 5.1, 1.5-17.1). Emergency surgery (OR 3.0, 1.4-6.4), abdominal
      surgery (OR 2.6, 1.0-6.8) and number of surgical interventions (OR 2.5, 1. 1-6.1)
      were the variables related to surgery that significantly increased the risk of
      sepsis. Both the study on the Efficacy of Nosocomial Infection Control (SENIC)
      and the National Nosocomial Infections Surveillance indices showed a
      statistically significant trend with sepsis. CONCLUSION: Patient-related factors
      appear to represent the greatest risk for developing postoperative nosocomial
      sepsis, rather than factors associated with the surgery.

PMID- 10931055
TI  - Impact of the '2 week wait' directive for suspected cancer on service provision
      in a symptomatic breast clinic.
AB  - BACKGROUND: The '2 week wait' directive (Health Service Circular (HSC) 1998/242)
      guaranteeing that 'everyone with suspected breast cancer will be able to see a
      specialist within two weeks of their general practitioner (GP) deciding they need
      to be seen urgently' is a unique audited approach to access for the British
      National Health Service, the effects of which have been assessed in a non
      academic symptomatic breast clinic. METHODS: New GP referrals (n = 607) were
      reviewed prospectively in two comparable 3-month intervals, beginning 1 April
      1998 and 1 April 1999, to determine the probability of a breast cancer diagnosis
      from the referral letter and the effects of the directive on waiting times for
      appointments and utilization of clinics. RESULTS: The urgency of referral was not
      specified in 53 per cent of GP referrals. For the 'urgent' cases (25 per cent of
      all new referrals) the probability of a final diagnosis of breast cancer was
      0.19. The breast specialists prospectively achieved a rate of 0.26 from 99 per
      cent of the same referral letters. 'Urgent' referrals did not wait significantly
      longer in 1999 (median 9 versus 10 days) but waiting times for new appointments
      overall increased (13 versus 16 days; P < 0.01), and this was greatest for
      'routine' [14] versus 21 days; P < 0.001). These changes were caused by an
      increase in the number of clinic appointments, due to significant increases in
      median number of visits to diagnosis or discharge and clinic non-attendance in
      1999, resulting in overbooking. Telephonic communications were associated with
      faster median access times (fax 8 days; telephone 2 days), relative to mailed
      [19] days) (P < 0.01). CONCLUSION: Breast specialists were better overall at
      assessing the probability of a breast cancer diagnosis. The waiting time for
      'urgent' appointments was unchanged following HSC 1998/242, but there was an
      increased wait for other patients, especially those assessed as having a lower
      probability of cancer.

PMID- 10931056
TI  - Cholecystectomy, peptic ulcer disease and the risk of adenocarcinoma of the
      oesophagus and gastric cardia.
AB  - BACKGROUND: Gastro-oesophageal reflux is a strong risk factor for oesophageal
      adenocarcinoma. Bile and pancreatic enzymes may be particularly carcinogenic.
      Cholecystectomy causes an increased gastric level of these constituents. A
      decreased risk of oesophageal adenocarcinoma has been observed in persons
      infected with cagA-positive Helicobacter pylori. There is a strong correlation
      between ulcer disease and Helicobacter pylori infection. The aim of this study
      was to determine whether previous cholecystectomy or peptic ulcer disease affects
      the risk of oesophageal carcinoma. METHODS: Data were collected as a nationwide
      population-based case-control study in Sweden between 1995 and 1997. Multivariate
      adjusted odds ratios (ORs) were calculated with logistic regression. RESULTS:
      There was no statistically significant association between cholecystectomy and
      the risk of oesophageal carcinoma. Among persons with previous peptic ulcer, the
      adjusted OR for oesophageal adenocarcinoma was below unity (OR = 0.6, 95 per cent
      confidence interval 0.3-1.1). The relative risk estimates for cardia
      adenocarcinoma and oesophageal squamous cell carcinoma were close to unity.
      CONCLUSION: Cholecystectomy, despite its effect on the composition of gastric
      juice, does not appear to increase the risk of adenocarcinoma of the oesophagus
      or gastric cardia. While the data do not contradict a protective effect of H.
      pylori, the results are also consistent with absence of such an effect.

PMID- 10931057
TI  - Role of xanthine oxidase in small bowel mucosal dysfunction after surgical
      stress.
AB  - BACKGROUND: The small intestine is highly susceptible to surgical stress even at
      remote locations. An earlier study using a rat model indicated that oxidative
      stress plays an important role in this process. The enzyme xanthine oxidase is an
      important source of free radicals in the small intestine. The role of this enzyme
      in intestinal damage after surgical stress was examined. METHODS: Rats pretreated
      with xanthine oxidase inhibitors were subjected to surgical stress by opening the
      abdomen and handling the intestine, as done during laparotomy. Enterocytes at
      various stages of differentiation were isolated and the protection offered by
      xanthine oxidase inhibitors against damage due to surgical stress was determined
      and compared with normal controls. Protection against ultrastructural changes to
      the mucosa, as well as mitochondrial function was examined. RESULTS: Surgical
      stress affected both the villus as well as crypt cells, causing increased
      superoxide generation, accompanied by increased activity of xanthine oxidase.
      Xanthine oxidase inhibitors ameliorated the increased superoxide generation, and
      protected against mitochondrial damage and ultrastructural changes in the
      intestine. CONCLUSION: Surgical stress affects both the villus and crypt cell
      populations in the small intestine. The enzyme xanthine oxidase maybe an
      important mediator of surgical stress in the intestine.

PMID- 10931058
TI  - Oesophageal resection for high-grade dysplasia in Barrett's oesophagus.
AB  - BACKGROUND: The aims of this study were to evaluate the prevalence of invasive
      cancer in patients with high-grade dysplasia in Barrett's oesophagus and to
      verify whether a second endoscopy with multiple biopsies could improve the
      accuracy of preoperative diagnosis. In addition, the mortality, morbidity and
      survival rates in patients with high-grade dysplasia having oesophageal resection
      were recorded. METHODS: Fifteen patients were observed from 1982 to 1998; the
      first seven patients were offered primary oesophageal resection after diagnosis.
      The other eight patients underwent a second endoscopy with a median of 12
      biopsies examined. All later underwent oesophageal resection. RESULTS: Invasive
      adenocarcinoma was found in five patients, with a minimal difference between the
      first and second periods (two of seven versus three of eight). There were no
      perioperative deaths. Early morbidity was observed in eight patients and late
      morbidity in four. The actuarial survival rate was 79 per cent at 5 years. The
      Karnofsky status was unchanged from preoperative values in 13 of 15 patients
      after a median follow-up of 46 months. CONCLUSION: These patients with high-grade
      dysplasia had a 33 per cent probability of harbouring invasive oesophageal
      carcinoma but even a second endoscopy failed to identify patients with invasive
      tumour. Oesophagectomy was performed with no deaths and remains a rational
      treatment in patients fit for surgery.

PMID- 10931059
TI  - Preoperative risk analysis in patients with adenocarcinoma or squamous cell
      carcinoma of the oesophagus.
AB  - BACKGROUND: The outcome after oesophagectomy depends not only on the surgical
      procedure itself but can be improved by the selection of patients based on a
      preoperative risk score. METHODS: In order to compare the preoperative risk for
      different histological subtypes of oesophageal carcinoma, 221 patients with a
      squamous cell carcinoma (SCC) and 104 patients with an adenocarcinoma (AC) were
      enrolled in a prospective study. The preoperative assessment included
      socioeconomic status, alcohol and tobacco consumption, general and nutritional
      status, and pulmonary, cardiovascular, hepatic and renal function. RESULTS: More
      patients with an SCC were 'blue collar' and with an AC were 'white collar'
      workers (P < 0.001). Alcohol and tobacco consumption was higher in patients with
      an SCC (P < 0.01 and P < 0.05 respectively). The preoperative forced expiratory
      volume, arterial partial pressure of oxygen and the aminopyrine breath test
      showed more severely compromised pulmonary and hepatic function in patients with
      an SCC (P < 0.05 for all variables). Some 50 per cent of patients with an AC were
      overweight with a higher body mass index (P < 0.001). More patients with an AC
      had severely impaired cardiac function (P < 0.01). CONCLUSION: Patients with SCC
      and AC of the oesophagus differed regarding their socioeconomic and preoperative
      risk factors for surgery.

PMID- 10931060
TI  - Multicentre study of thyroid nodules in patients with Graves' disease.
AB  - BACKGROUND: The association of Graves' disease with thyroid nodules and thyroid
      carcinoma is rarely reported. The incidence seems to be increasing according to
      recent literature. The aim of this multicentre study was to review patients who
      had surgery for Graves' disease associated with thyroid nodules, and to evaluate
      the risk of thyroid carcinoma. METHODS: A retrospective study was made of 557
      consecutive patients who underwent operation for Graves' disease between 1991 and
      1997 in five endocrine surgery departments. Each patient underwent clinical,
      biochemical, ultrasonographic and scintigraphic evaluation. None of the patients
      had had previous radioactive iodine therapy or external irradiation. Surgery
      consisted of either a subtotal or total thyroidectomy. RESULTS: Nodules were
      observed before operation in 140 patients (25.1 per cent). Thyroid carcinoma was
      diagnosed in 21 patients (15.0 per cent), always inside a nodule. The incidence
      of thyroid carcinoma associated with Graves' disease was 3.8 per cent (21 of 557
      patients): 20 papillary and one follicular carcinoma. The carcinoma was
      multifocal in two patients. Tumour diameter ranged from 2 to 25 mm. A nodule was
      palpable in four patients. CONCLUSION: This multicentre study of patients having
      thyroidectomy for Graves' disease showed that 3.8 per cent had a carcinoma; the
      rate of carcinoma in cold nodules was 15.0 per cent. Surgery should be advised in
      any patient with Graves' disease and a thyroid nodule; the operation should be
      total thyroidectomy.

PMID- 10931062
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931061
TI  - CORRESPONDENCE: the editors welcome topical correspondence from readers relating
      to articles published in the journal. Letters should be no more than 250 words in
      length and should be typed on A4-sized paper in double spacing venous ulcer
      healing by four-layer compression bandaging is not influenced by the pattern of
      venous incompetence

PMID- 10931063
TI  - Comparison of cognitive function and quality of life after endovascular or
      conventional aortic aneurysm repair.

PMID- 10931064
TI  - Diagnostic accuracy of needle-localized open breast biopsy for impalpable breast
      disease.

PMID- 10931065
TI  - Electronic evaluation of the value of double gloving.

PMID- 10931066
TI  - Smacking.

PMID- 10931068
TI  - Implications of attachment style for patterns of health and illness.
AB  - There is substantial evidence that health status and health outcomes are related
      to the availability and quality of personal relationships. The proposition that
      attachment relationships in childhood and adolescence have health-related
      implications fits within this research tradition, and has guided recent attempts
      to develop models linking attachment style with emotional regulation, coping
      mechanisms, and illness behaviours. The present paper discusses these theoretical
      models, together with relevant empirical findings. It is argued that measures of
      attachment security are related to symptom-reporting, health-care utilization,
      and restriction of normal activities, and that these links can be explained, in
      part, by individual differences in emotional and behavioural responses to stress.
      It is further noted that researchers have proposed physiological and biochemical
      pathways which may explain some of the effects of attachment style on physical
      health. The quality of parent-child attachment also predicts family responses to
      children's illness, as reflected in parents' visitation rates and in family
      participation in studies of health and illness. The implications of the findings
      for research and for practice in the health professions are briefly discussed.

PMID- 10931067
TI  - Characteristics of paediatric home care provision: the two dominant models in
      England.
AB  - AIM: To describe characteristics of paediatric home care teams BACKGROUND: Home
      care provision is increasing and recent government initiatives such as support
      for Princess Diana Memorial Fund nursing teams will provide additional impetus to
      universal provision. However, little is known about the characteristics of
      paediatric home care teams. METHOD: A postal survey of all services in England (n
      = 137) listed in the 13th edition of RCN 1996 Directory of Community Children's
      Nursing Services was undertaken. A response rate of 85.5% was achieved. FINDINGS:
      More than half (54.6%) of the teams had been founded after 1990. Most (72.2%)
      were managed through paediatric or child health directorates and most (77.8%)
      were based in hospitals. The size of teams varied enormously (range 1-22; median
      3). Only a small (5.6%) minority of teams provided care at night although over a
      third (37%) reported making special arrangements for terminally ill children.
      CONCLUSION: The survey revealed two dominant models of paediatric home care: the
      community model with strong links to primary health care and other local
      provisions and the hospital outreach model with strong links to the hospital
      service. A number of weaknesses in current provision are identified: variability
      in geographical coverage; undesirably low core staffing numbers; poor 24-h
      coverage; and potentially compromised staff skills and knowledge. The need for
      research to clarify the strengths of the different models and their effectiveness
      is highlighted.

PMID- 10931069
TI  - Factors affecting language development in West African children: a pilot study
      using a qualitative methodology.
AB  - Data on referral patterns to pre-school facilities for speech- and language
      delayed children suggest that West African children are over represented relative
      to other ethnic/language groups. This study was set up as a pilot to explore some
      of the issues which distinguish this group of children and their families. A
      qualitative methodology was adopted to access the views of a small group of
      parents (nine) and professionals with direct experience of these services
      (three). Between them the parents had a total of 11 children who had received
      speech and language therapy services. Extensive in-depth interviews were
      transcribed and coded. The families are predominantly well educated with high
      expectations for their children. Their beliefs about child development in general
      and language development often differed from those of the professionals
      interviewed. For example, parents saw little direct link between very early
      language stimulation and subsequent school performance. West African parents also
      perceived that they had different (higher) expectations of behaviour than other
      families. It was generally accepted by all parties that the West African
      community experiences a high degree of stress resulting from a combination of
      interacting factors, namely pressures relating to employment, to immigration
      status, to matters financial and to expectations from family back in their own
      country. It is unclear exactly how these impact on the development of the child
      but there is an awareness that there may be a negative effect of such stress and
      that children's speech and language development may be one aspect of development
      that is affected. As a result of this pilot study a number of mechanisms relating
      to the relationship between environment factors and language development are
      proposed and suggestions are made regarding service provision for this community.

PMID- 10931070
TI  - Coping when a child has a disability: exploring the impact of parent-to-parent
      support.
AB  - AIM: To explore the impact of parent-to-parent support when a child is born with
      a disability. DESIGN: The research approach was qualitative. Data were collected
      retrospectively and were derived from in-depth interviews with parents. The audio
      taped interviews were transcribed and then analysed using constant comparative
      procedures. SETTING: Scotland. PARTICIPANTS: The parents of 63 children born with
      a congenital upper limb deficiency. FINDINGS: The early weeks and months
      following the birth of their baby was a difficult and emotional time for most
      parents. Feelings of isolation were common and there was a lot of concern about
      what the future would hold. Although a certain amount of support was derived from
      contact with family, friends and health professionals, parents did not generally
      obtain the level of support that was required from these sources. Contact with
      other parents of limb-deficient children, however, clearly exerted a powerful
      stress-buffering influence, providing much needed emotional, social and practical
      support. CONCLUSIONS: This study suggests that parents of children with special
      needs are uniquely qualified to help each other. The challenge is to ensure that
      health professionals are aware of the potential benefits of parent-to-parent
      support and provide parents with information about appropriate local
      organizations/ contacts.

PMID- 10931071
TI  - Validation of the Warwick Child Health and Morbidity profile in routine child
      health surveillance.
AB  - OBJECTIVE: To further validate a simple instrument for the measurement of parent
      reported health and morbidity in infancy and childhood when used in routine child
      health surveillance as part of a whole year birth cohort study. Setting The
      socially and ethnically diverse city of Coventry. METHODS: Health visitors
      administered the Warwick Child Health and Morbidity profile (WCHMP), incorporated
      into the Parent Held Record (PHR), to the parents of infants born in 1996 and
      enrolled in the Coventry Cohort study as part of routine child health
      surveillance at 8 weeks and 8 months. Criterion validity was estimated for
      Hospital admission status and immunization status against health records and
      validity against medically plausible constructs was tested by comparing responses
      between domains and between the two data collection points for the whole cohort.
      RESULTS: Criterion validity for parental reporting of immunization status (Kappa
      0.824 [95% CIs, 0.708, 0.940]) and hospital admission (Weighted Kappa 0.987 [95%
      CIs, 0.977, 0.997]) were high. There was a high level of concordance between
      parental responses to related domains and the medically plausible constructs. The
      proportion of parents reporting chronic illness, acute significant illness,
      chronic illness and accidents increased as expected between 8 weeks and 8 months.
      As expected, adverse outcomes at 8 weeks were associated with an increased risk
      of the same outcomes at 8 months. CONCLUSIONS: The WCHMP is a simple measure of
      parent-reported health and illness which was shown to be reliable and valid with
      low inter-observer variation on initial field-testing. Further validation of the
      WCHMP, incorporated into the PHR, in a routine child health surveillance
      programme demonstrates its suitability for use in infancy to collect cross
      sectional and longitudinal health and morbidity data for research and service
      planning purposes.

PMID- 10931072
TI  - West African children in private foster care in City and Hackney.
AB  - A unique feature of some Africans who come to study and work in Britain is the
      practice of making private arrangements to send their children to live with
      foster parents who assume full parental rights. Six hundred randomly selected
      African families, with a child born between June 1988 and May 1991, resident in
      one Health Authority, were sent a questionnaire to elicit the proportion of
      children who had been in private foster care and to gain information on the
      knowledge and attitudes to fostering and day care provision. Families with
      children in foster care were asked additional questions about their experiences.
      Two hundred and six (34%) of the questionnaires were analysed. Seventy-six per
      cent of the respondents were from Nigeria, 65% had already heard about private
      fostering and 29 (14%) had sent one of their children to private foster care.
      Only one family felt that foster care was a suitable option; the reminder would
      have preferred alternative facilities such as nursery placement. Of the 29
      children in foster care, nine parents said their children were unhappy and five
      rated the foster parents as bad. Contrary to popular belief, most children were
      visited fortnightly, some more frequently and only two never visited. Private
      fostering in this group of children was found to be less common than in earlier
      studies.

PMID- 10931073
TI  - Anti-thyroid drug treatment before radioiodine in patients with Graves' disease:
      soother or menace?

PMID- 10931074
TI  - Lack of consensus in Europe in the management of nontoxic multinodular goitre.

PMID- 10931075
TI  - Management of the nontoxic multinodular goitre: a European questionnaire study.
AB  - BACKGROUND AND OBJECTIVE: The optimum management strategy for the patient with a
      multinodular nontoxic goitre is still a matter of debate. Our aim was to assess
      the attitudes towards management of such patients throughout Europe by means of a
      questionnaire. DESIGN: The questionnaire was circulated to all clinician members
      of the European Thyroid Association (ETA). A case report was followed by
      diagnostic investigations and choice of therapy in the index case (a 42-year-old
      woman with an irregular nontender bilaterally enlarged thyroid of 50-80 g and no
      clinical suspicion of malignancy). Eleven variations of the basic case report
      were proposed in order to evaluate the impact on management of each alteration.
      SUBJECTS AND METHODS: One hundred and sixty-seven members replied to the letter,
      and 120 individuals from 22 countries completed the questionnaire (corresponding
      to approximately two-thirds of the clinical members of the ETA). RESULTS: Based
      on the index case, serum TSH was the routine choice of 100%, and serum free T4/T4
      index was included by 74%. Serum TPO autoantibodies, Tg autoantibodies and
      calcitonin were measured by 65%, 49% and 32%, respectively. The median number of
      blood tests used was four (range 1-11). Considerable intercountry variations were
      seen in the preferred imaging methods. Ninety-one percent of the clinicians would
      use at least one imaging modality. Ultrasound (US) was used by 84%, thyroid
      scintigraphy by 76%, and both methods by 69%. US had first priority (53% vs. 19%
      for scintigraphy). If scintigraphy was performed, fine-needle aspiration cytology
      was routinely used by 17% (inhomogeneous uptake) and 95% (dominant 'cold' area),
      and 63% used US-guidance. L-T4 treatment was supported by 52% of the clinicians,
      iodine supplementation by 4%, radioiodine by 6% and surgery by 10%. In the case
      of a suppressed serum TSH, radioiodine treatment was preferred by 44%, while
      surgery was the favoured recommendation in four clinical variations with a large
      goitre or suspicion of malignancy. Marked differences between the countries were
      suggested by L-T4 therapy being the dominant treatment in Italy, France and
      Germany in contrast to the prevailing use of radioiodine in Denmark and a wait
      and see policy in the UK. CONCLUSIONS: Fundamental differences between European
      countries exist as regards diagnosis and treatment of the multinodular nontoxic
      goitre suggesting difficulties in reaching a consensus.

PMID- 10931076
TI  - Increased prevalence of thyroid autoimmunity in patients successfully treated for
      Cushing's disease.
AB  - BACKGROUND: Cushing's disease is characterized by abnormalities of immune
      function. OBJECTIVE: To evaluate the prevalence of autoimmune thyroid diseases in
      patients with Cushing's disease (CD), after successful treatment and the possible
      association between previous nodular goitre or positive thyroid autoantibodies
      during the active phase of CD and the subsequent development of autoimmune
      thyroid diseases after cure. SUBJECTS AND METHODS: Twenty patients with CD and 40
      sex- and age-matched healthy controls were considered for the study. In CD
      patients, thyroid ultrasonography and measurement of circulating free thyroxine
      (fT4), free triiodothyronine (fT3), thyroid stimulating hormone (TSH),
      antithyroglobulin (anti-Tg) and antithyroperoxidase (anti-TPO) antibodies were
      performed at diagnosis and 6 months after disease cure while in controls they
      were performed only at study entry. RESULTS: Serum fT3, and fT4 levels were
      similar in patients, either during the active phase or after cure of the disease,
      and controls. Conversely, in the patients, serum TSH levels were significantly
      lower during active disease (0. 4 +/- 0.05 mU/l, P = 0.001) and significantly
      higher after disease cure (4.7 +/- 0.1 mU/l, P < 0.001) than in controls (2.3 +/-
      0.4 mU/l). Four patients (20%) and 11 controls (27.5%) had positive anti-Tg
      and/or anti-TPO titre at study entry, while eight patients (40%) developed
      positive anti-Tg and/or anti-TPO titre after disease cure. The prevalence of
      positive antithyroid antibodies titre in cured CD patients was significantly
      higher than that observed in the same patients during the active disease (P =
      0.008) and in controls (P = 0.031). A significantly higher prevalence of
      autoimmune thyroiditis was found in patients cured from CD (35%) than in patients
      with active CD (0%) (P = 0.016) and in controls (10%) (P = 0.031). A significant
      association was found between the presence of autoimmune thyroiditis after CD
      cure and the presence of a previous nodular goitre (P = 0.017) or positive
      thyroid autoantibodies titre (P = 0.007) during the active phase of the disease.
      CONCLUSION: Patients successfully treated for Cushing's disease have an increased
      prevalence of thyroid autoimmunity and autoimmune thyroiditis as compared to a
      control population. Therefore, patients with hypercortisolism need an accurate
      evaluation of thyroid function after remission of the disease in order to prevent
      the eventual onset of subclinical or overt post-thyroiditis hypothyroidism.

PMID- 10931077
TI  - Prevalence and characteristics of postpartum thyroid dysfunction in Sao Paulo,
      Brazil.
AB  - OBJECTIVE: Postpartum thyroid dysfunction (PPTD) is an autoimmune disorder
      characterized by the development of transient hyperthyroidism and, more
      frequently, hypothyroidism (or both) during the first six months of the puerperal
      period. A variable incidence has been reported in part because of differences in
      the number of women studied, the frequency of thyroid assessment postpartum,
      diagnostic criteria and methodology. The aim of this study was to evaluate
      thyroid function, ultrasound images and titre of autoantibodies against thyroid
      antigens in a cohort of pregnant women who met the criteria of 'normal' thyroid
      gland structure on clinical examination and imaging and normal thyroid function
      tests without a significantly positive anti-thyroid peroxidase (TPO) antibody
      titre (i.e. < 100 U/ml) in the first trimester. DESIGN AND PATIENTS: Eight
      hundred nulliparous or multiparous (one to seven previous pregnancies) pregnant
      women (age 26.1 +/- 4.8 years, mean +/- SD), were submitted to clinical,
      laboratory and ultrasonographic examination in the first trimester of pregnancy.
      Among these forty-six patients were excluded because of thyroid dysfunction,
      ultrasound structural abnormalities or a positive anti-TPO antibody titre (> 100
      U/ml). A total number of 754 women were available for further studies in the
      postpartum period. A relatively large number of these patients (386) were lost
      for follow-up either before or after delivery. MEASUREMENTS: A cohort of 368
      puerperal women was followed up regularly at 3, 6, 12 and 24 months after
      delivery, with periodic thyroid function tests, random urine iodine measurements,
      assays for serum autoantibodies against thyroid antigens and imaging by
      ultrasound. RESULTS: The provisional diagnosis of PPTD was established in 78 out
      of 368 who had positive anti-TPO levels and ultrasonographic thyroid structural
      changes. Twenty-nine of these patients had a transient rise of anti-TPO
      autoantibodies characterizing an autoimmune reaction. These autoantibodies levels
      progressively declined or became negative. Moreover none of these patients had
      evidence for altered thyroid function during the 18-24 months of follow-up. The
      remaining 49 patients (13.3%) progressively developed thyroid function
      abnormalities (mainly hypothyroidism) indicating the presence of thyroid gland
      changes due to PPTD. Further follow-up studies indicated that at 18-24 months, 42
      patients had serum levels of anti-TPO-Ab that were more elevated, as compared
      with the first year values. Predictive factors found during pregnancy for
      developing PPTD were: (1) relatively low levels of anti-TPO, between 60 and 100
      U/ml (odds ratio 3.1 : 1), and (2) ultrasonographic thyroid structural changes in
      the first trimester (odds ratio 6.4 : 1). CONCLUSIONS: We conclude that the
      prevalence of postpartum thyroid dysfunction in our geographical area ranges from
      6.7% to 13.3%, considering, respectively, all pregnant women that were examined
      (n = 754) or only the number of puerperal women actually followed-up (n = 368). A
      transient form of thyroid autoimmune reaction characterized by elevated serum
      levels of anti-TPO that progressively declined or disappeared was observed in 29
      puerperal women. Sonographic structural and echogenicity changes in the thyroid
      gland and borderline positive anti-TPO levels (between 60 and 100 U/ml) during
      pregnancy were considered to be of predictive value for development of postpartum
      thyroid dysfunction.

PMID- 10931078
TI  - Reversible hypogonadotrophic hypogonadism in sexually infantile male thalassaemic
      patients with transfusional iron overload.
AB  - OBJECTIVE: To determine the severity and reversibility of the lesion in the
      hypothalamic-pituitary (H-P) axis of male transfusion-dependent thalassaemic
      patients with failed puberty (FP). DESIGN AND SUBJECTS: The hypothalamic
      pituitary axes of 20 male thalassaemic patients (study group) were compared with
      two male subjects with idiopathic hypogonadotrophic hypogonadism (IHH) and five
      prepubertal healthy siblings (control group). GnRH-gonadotrophin insufficiency
      was characterized by nocturnal 12 h ultradian gonadotrophin profiles followed by
      a 100 microg GnRH bolus test (GBT) 4-6 times at 6 monthly intervals. Thalassaemic
      and IHH patients were then subjected to pulsatile subcutaneous GnRH infusions
      every 120 minutes for 3 months. Ultradian gonadotrophin profiles and GBT were
      repeated after 6 weeks of GnRH infusion and again at 3 months following infusion.
      MEASUREMENTS: FSH and LH were measured by radio-immunoassay. Ferritin was assayed
      by an immunoradiometric method. RESULTS: Patients with IHH who were apulsatile
      prior to infusion, developed normal gonadotrophin pulses with marked increment in
      their gonadotrophin responses to the GBT after 3 months of GnRH infusion. In
      contrast, the thalassaemic patients with apulsatile failed puberty (AFP) remained
      apulsatile (nonresponders) and had no increment in their gonadotrophin responses
      to the GBT after GnRH infusion. All patients with pulsatile failed puberty (PFP)
      had abnormal gonadotrophin pulses prior to GnRH infusion. Their pulse defects
      were either totally or partially corrected (responders) following infusion. The
      serum ferritin levels (9500 +/- 500 microg/l vs. 5966.67 +/- 1139 microg/l; P <
      0.01) and percentage of organ dysfunction (87% vs. 17%; P < 0.01) were higher in
      the nonresponders than the responders. CONCLUSIONS: This study shows that
      thalassaemic patients with severe organ damage and iron overload are likely to be
      apulsatile with irreversible damage to their hypothalamo-pituitary axis, while
      those with less severe iron overload are likely to have potentially reversible
      hypogonadotrophic hypogonadism (HH). Our results also suggest that gonadotrophin
      pulse parameters, rather than the gonadotrophin response to a GnRH bolus
      following prolonged pulsatile GnRH infusion, may be more useful in discriminating
      reversible from irreversible hypogonadotrophic hypogonadism.

PMID- 10931079
TI  - Intramuscular testosterone undecanoate with or without oral levonorgestrel: a
      randomized placebo-controlled feasibility study for male contraception.
AB  - OBJECTIVE: Approaches to hormonal male contraception are based on injectable
      testosterone esters alone or in combination with gestagens or GnRH analogs but
      the short half-life of clinically used testosterone esters have long hindered
      further development. This study was designed to prove the efficacy of the long
      acting testosterone undecanoate ester (TU) alone or in combination with oral
      levonorgestrel (LNG) in a phase II clinical trial. DESIGN AND SUBJECTS: Twenty
      eight healthy men were randomized to receive injections of 1000 mg TU every 6
      weeks in combination with daily oral LNG (250 microg) or daily oral placebo
      treatment over a period of 24 weeks, followed by a control period of 28 weeks.
      MEASUREMENTS: During the course of the study semen analysis, reproductive hormone
      analysis, analysis of clinical chemistry and lipid parameters, well-being and
      sexual function, sonography of scrotal contents and prostate were performed.
      RESULTS: Marked suppression of gonadotrophins in both treatment groups resulted
      in azoospermia in 8/14 and 7/14 volunteers and severe oligozoospermia (< 3 x
      1012/l) in 4/14 and 7/14 in the placebo and gestagen treated groups,
      respectively. Time to induction of azoospermia (mean +/- SEM) was not
      significantly different between the placebo (week 19.5 +/- 2.2) and LNG groups
      (week 15.4 +/- 2.2). During the whole treatment period mean testosterone serum
      concentrations remained within normal limits. Although not significant, it was
      evident that volunteers who became azoospermic had a better suppression of
      gonadotrophins and lower SHBG levels during treatment compared to non-azoospermic
      volunteers. Despite better gonadotrophin suppression in the LNG group no
      significant differences compared to placebo could be observed in the extent and
      kinetics of suppression of spermatogenesis, thus not demonstrating a major
      beneficial effect of LNG in the combination with injectable TU. Treatment led in
      both groups to a decrease of HDL and Lp(a) which was more pronounced in the LNG
      group (P > 0.05). CONCLUSION: Treatment with 1000 mg testosterone undecanoate
      injected at 6 weekly intervals or in combination with levonorgestrel showed
      suppression of spermatogenesis comparable to weekly injections of 200 mg
      testosterone enanthate. Because of its long half-life and in the absence of
      severe side-effects, testosterone undecanoate can be considered as first choice
      testosterone ester in further studies of hormonal male contraception.

PMID- 10931080
TI  - The effect of quinagolide and cabergoline, two selective dopamine receptor type 2
      agonists, in the treatment of prolactinomas.
AB  - OBJECTIVE: To compare effectiveness and tolerability of quinagolide (CV 205-502)
      and cabergoline (CAB) treatments in 39 patients with prolactinoma. STUDY DESIGN:
      All 39 patients were treated first with quinagolide for 12 months and then with
      cabergoline for 12 months. A wash-out period was performed in all patients after
      12 months of both treatments in order to evaluate recurrence of
      hyperprolactinaemia. PATIENTS: Twenty-three patients with microprolactinoma
      (basal serum PRL levels 1620-18750 mU/l) and 16 patients with macroprolactinoma
      (basal serum PRL levels 4110-111000 mU/l), previously shown to be intolerant of
      bromocriptine. All patients had gonadal failure and 11 patients with
      macroprolactinoma had visual field defects. Five patients with macro- and one
      with microprolactinoma had previously undergone surgery. STUDY PROTOCOL: The
      starting doses of quinagolide and CAB were 0.075 mg/day and 0.5 mg/week,
      respectively, subsequently increased up to 0.6 mg once daily and 1.5 mg twice
      weekly, respectively. Serum PRL levels were measured monthly for the first 3
      months and then quarterly for 12 months. PRL levels were assayed weekly for the
      first month and then monthly during the wash-out period. Tumour shrinkage was
      evaluated by serial magnetic resonance imaging (MRI) studies of the hypothalamus
      pituitary region at study entry and after 6 and 12 months of both treatments in
      micro- and macroprolactinomas. RESULTS: After 12 months of quinagolide treatment,
      serum PRL levels normalized in all 23 patients with microprolactinoma (100%) and
      in 14 out of 16 with macroprolactinoma (87.5%). A tumour volume reduction of
      greater than 80% was documented by MRI studies in five of 23 (21.7%) patients
      with microprolactinoma and in four of 16 (25%) with macroprolactinoma. All
      patients had recurrence of hyperprolactinaemia after 15-60 days withdrawal of
      quinagolide treatment. However, before starting CAB treatment basal PRL levels
      were significantly lower than before quinagolide treatment both in
      microprolactinomas (4667.4 +/- 714.7 vs. 2636.1 +/- 262.3 mU/l, P = 0.006) and in
      macroprolactinomas (24853.1 +/- 7566.7 vs. 3576.6 +/- 413.0 mU/l, P = 0.013).
      After 12 months of CAB treatment, serum PRL levels normalized in 22 out of 23
      patients with microprolactinoma (95.6%) and in 14 out of 16 with
      macroprolactinoma (87.5%). No difference in PRL nadir was found after quinagolide
      and CAB treatments both in micro 174.6 +/- 30.6 vs. 169.8 +/- 37.9 mU/l, P = 0.5)
      and in macroprolactinomas (277.5 +/- 68.4 vs. 341.8 +/- 95.2 mU/l, P = 0.6). A
      tumour volume reduction of greater than 80% was documented by MRI studies in
      seven other patients with microprolactinoma (30.4%) and in five other patients
      with macroprolactinoma (31.2%). After CAB treatment, further tumour shrinkage
      ranging 4-40% and 2-70% was observed in 12 micro- and seven macroprolactinomas,
      respectively. The percentage of tumour shrinkage after CAB was significantly
      higher than that observed after quinagolide in microprolactinomas (48.6 +/- 9.5
      vs. 26.7 +/- 4. 5%, P = 0.046) but not in macroprolactinomas (47.0 +/- 10.6 vs.
      26.8 +/- 8.4%, P = 0.2). The withdrawal from CAB treatment, induced an increase
      in serum PRL levels in all macroprolactinomas between 15 and 30 days, in 15 out
      of 23 microprolactinoma after 30 days, and in four patients after 2-4 months. In
      the remaining four patients serum PRL levels remained normal after 12 months of
      CAB withdrawal. Both compounds were tolerated satisfactorily by all patients. In
      the first week of quinagolide treatment, 12 patients reported nausea and postural
      hypotension, which spontaneously disappeared during the second-third week of
      treatment. None of the 39 patients reported side-effects during CAB treatment.
      CONCLUSIONS: Both quinagolide and CAB treatments, induced the normalization of
      serum PRL levels in the great majority of patients with prolactinoma. Tumour
      shrinkage was recorded in 22-25% of patients after quinagolide and in 30-31%
      after CAB treatment

PMID- 10931081
TI  - The somatotrophic system in patients with dilated cardiomyopathy: relation of
      insulin-like growth factor-1 and its alterations during growth hormone therapy to
      cardiac function.
AB  - OBJECTIVE: Treatment with human recombinant growth hormone has yielded
      conflicting results in patients with congestive heart failure. In addition,
      growth hormone resistance has been reported in severe heart failure. Therefore,
      the purpose of this study was to evaluate the somatotrophic axis and effects of
      growth hormone on haemodynamics in patients with heart failure due to dilated
      cardiomyopathy. DESIGN: Randomized, double-blind, placebo-controlled trial.
      PATIENTS: Fifty clinically-stable patients with moderate heart failure (mean left
      ventricular ejection fraction = 26 +/- 2%) due to dilated cardiomyopthy were
      examined. MEASUREMENTS: Patients were randomly assigned to treatment with placebo
      or 2 IU/d sc human recombinant growth hormone for a mean of 14 weeks. Cardiac
      size and function were evaluated by magnetic resonance imaging. Central
      haemodynamics were obtained by right heart catheterization. Measurements of
      plasma noradrenaline, serum insulin-like growth factor-1, and insulin-like growth
      factor binding protein-3 were performed by standard assays at baseline and at the
      end of the treatment period. RESULTS: The severity of heart failure as determined
      by stroke volume, left ventricular end diastolic diameter and plasma
      noradrenaline concentrations correlated significantly to baseline serum insulin
      like growth factor-1 levels (each P < 0.05). The growth hormone-induced increase
      of insulin-like growth factor-1 predicted the changes in ejection fraction (P <
      0.05). A significant increase in ejection fraction of 7% was observed in patients
      whose insulin-like growth factor-1 increased by more than the median increase in
      comparison to the patients with an increase below the median (+ 4.0 +/- 2.3% vs. 
      3.0 +/- 1.8%; P = 0.03). CONCLUSIONS: Serum levels of insulin-like growth factor
      1, reflecting growth hormone secretion, are diminished in relation to the
      severity of heart failure in patients with dilated cardiomyopathy. Growth hormone
      induced increases of insulin-like growth factor-1 of more than 77 ng/l caused
      significant improvement of ejection fraction.

PMID- 10931082
TI  - Urinary GH and IGF-I excretion in nine year-old children: relation to sex,
      current size and size at birth.
AB  - OBJECTIVES: To study the relationship of 24-hour urinary growth hormone (GH) and
      IGF-I excretion in childhood to sex and body size. To test the hypothesis that
      small size at birth followed by postnatal catch-up growth is associated with
      elevated IGF-I production. DESIGN AND SUBJECTS: Follow-up study of a cohort of
      183 healthy children born in Salisbury, UK. MEASUREMENTS: Weight and height, 24-h
      urinary growth hormone (uGH) and IGF-I (uIGF-I) excretion, and systolic and
      diastolic blood pressures. RESULTS: At 9 years of age, 24-h uIGF-I excretion, but
      not uGH excretion, was strongly related to current weight (P < 0.001) and height
      (P < 0. 001). Urinary GH and IGF-I excretion were positively correlated (r =
      0.15, P = 0.05). Boys excreted more uIGF-I per unit uGH than girls (uIGF-I/uGH
      molar ratio 32.1 compared to 21.0; P for difference = 0. 002). There were no
      significant relationships of uGH, uIGF-I or uIGF-I/uGH molar ratio with
      birthweight, birthlength or head circumference at birth, nor with blood pressure
      at 9 years. 'Catch-up' growth, indicated by an increase in height SD scores
      between birth and 9 years, was associated with higher IGF-I excretion (P = 0.01)
      and occurred in children with taller parents (P < 0.001). CONCLUSIONS: Boys
      appear to be more sensitive to GH than girls, generating more uIGF-I in relation
      to uGH. Urinary IGF-I excretion at 9 years is related to both absolute height and
      to the degree of catch-up in height from birth. Our results suggest that IGF-I
      production is strongly influenced by genetic factors, but also by either the
      degree to which intrauterine growth falls short of genetic growth potential, or
      the process of postnatal catch-up growth that follows.

PMID- 10931083
TI  - Vasopressin and thirst in patients with posterior pituitary ectopia and
      hypopituitarism.
AB  - OBJECTIVE: Partial diabetes insipidus has been documented in patients with
      congenital hypopituitarism and posterior pituitary ectopia, some cases being
      clinically silent except for enuresis. The objective of our study was to evaluate
      vasopressin (AVP) secretion and thirst appreciation in hypopituitary patients
      with posterior pituitary ectopia. PATIENTS: Twelve males and three females, aged
      between 13 and 38 years (median 19 years). Eleven had multiple pituitary
      deficiencies, adequately replaced at the time of the study, and four were only
      growth hormone deficient. None of the patients suffered from polyuria, polydipsia
      or nocturnal enuresis. We tested the patients with a 5% NaCl infusion. Five
      patients with abnormal vasopressin production were also tested with
      nitroprusside, which affects baroceptor vasopressin secretion. RESULTS: We found
      that only two out of 12 patients had normal AVP secretion. Thirst assessment
      showed severe hypodipsia in one patient, hyperdipsia in three out of 15 and more
      subtle abnormalities in two out of 15 patients. Concordance was found between
      osmotically and baroceptor-stimulated vasopressin. CONCLUSIONS: Patients with
      posterior pituitary ectopia showed a high prevalence of subclinical subnormal
      vasopressin response to the osmolar stimulus and moreover an impairment of thirst
      appreciation. Our data on nonosmotically stimulated AVP release suggest the
      existence of a damage in the hypothalamic vasopressin secreting centres.

PMID- 10931084
TI  - Loss of heterozygosity in sporadic parathyroid tumours: involvement of chromosome
      1 and the MEN1 gene locus in 11q13.
AB  - OBJECTIVE: Hyperparathyroidism (HPT) is a common endocrine disorder. Several loci
      of genetic interest have been identified in parathyroid tumours, including the
      MEN1 gene locus at 11q13; the HPT-JT region at 1q21-q32; and a putative tumour
      suppressor gene on 1p. We analysed these intervals, which harbour known genes or
      putative loci associated with familial hyperparathyroidism, in order to clarify
      the involvement of the respective regions in parathyroid tumourigenesis. DESIGN:
      We performed loss of heterozygosity (LOH) studies on 33 sporadic parathyroid
      tumours using a PCR based technique. A total of 22 microsatellite markers were
      used to analyse loci at 11q13, 1q21-q32 and 1p. Ten markers located distal on 1p,
      eight markers encompassed the HPT-JT region at 1q21-q32 and four markers
      surrounded the MEN1 gene locus at 11q13. MEN1 mutations were screened for using
      Single Strand Conformation Polymorphism analysis (SSCP) and automated sequencing
      of SSCP variants. PATIENTS: Thirty-three parathyroid glands and the corresponding
      blood samples were obtained from 33 patients (26 females and seven males) who
      underwent parathyroidectomy for primary hyperparathyroidism. RESULTS: Loss of
      heterozygosity was detected in 13 of 33 (39%) cases at 11q13, 6 of 33 (18%) cases
      at 1p, and in three of 33 (9%) cases at 1q (in conjunction with 1p loss). Only
      one of the 18 tumours in which LOH was detected, showed LOH at both chromosome 1
      and chromosome 11. Additionally, those tumours found to exhibit LOH at 11q13 were
      screened for MEN1 mutations using single strand conformation polymorphism
      analysis (SSCP) and automated sequencing. Nine novel somatic mutations were found
      on the remaining allele in 13 (69%) tumours. CONCLUSIONS: This study consolidates
      the role of multiple loci in the pathogenesis of sporadic parathyroid tumours.
      The results indicate that there are at least two genetic loci involved in
      sporadic parathyroid tumourigenesis on chromosome 1, one of which has been linked
      to the distinct familial parathyroid condition, hyperparathyroidism-jaw tumour
      (HPT-JT) syndrome. The high frequency of loss of heterozygosity at 1p suggests
      the presence of a tumour suppressor at this locus.

PMID- 10931085
TI  - Vitamin D receptor gene start codon polymorphism (FokI) and bone mineral density
      in healthy male subjects.
AB  - OBJECTIVE: The genetic factors determining peak bone mineral density (BMD) in men
      are not well characterized. Recent studies have investigated the relationship
      between the start codon polymorphism (SCP) of the vitamin D receptor (VDR) gene
      and BMD in different populations. We have now examined the relationship between
      SCP of the VDR gene and BMD in a group of healthy Caucasian men from the north
      east of England. SUBJECTS: Ninety-six healthy men (median age 50, range 40.0-77.0
      years). MEASUREMENTS: Analysis of the FokI genotypes of SCP of the VDR and
      measurements of BMD at the femoral neck and lumbar spine were performed. RESULTS:
      FF, Ff and ff VDR FokI genotypes were found to have the highest, intermediate and
      the lowest lumbar spine BMD, respectively (Mean +/- SD, for FF 1.07 +/- 0.14, Ff
      1.05 +/- 0.16 and ff 0.95 +/- 0.10 g/cm2). There was a significant difference in
      spine BMD between FF and ff genotypes (P < 0.05, analysis of variance [ANOVA]),
      but no such difference was apparent between Ff and ff (P > 0.05, ANOVA).
      Interestingly, there was no association between FokI polymorphism and femoral
      neck BMD (Mean +/- SD, for FF 0.85 +/- 0.12, Ff 0.87 +/- 0.15 and ff 0.83 +/-
      0.15 g/cm2). The distribution of FokI VDR genotypes approached Hardy-Weinberg
      equilibrium and was similar to that reported for women from different ethnic
      groups, as the prevalence of FF and ff genotypes was 44% and 16%, respectively.
      CONCLUSION: The study shows that in this population of healthy men there is a
      weak association between lumbar spine bone mineral density and FokI restriction
      fragment length polymorphism at the translation initiation site of the vitamin D
      receptor gene.

PMID- 10931086
TI  - Characterization of pituitary function with emphasis on GH secretion in the
      chronic fatigue syndrome.
AB  - OBJECTIVE: Previous studies have revealed that hormonal disturbances may
      accompany the chronic fatigue syndrome (CFS). Changes in the secretion of the
      pituitary-adrenal axis have been demonstrated, as well as abnormalities in the GH
      IGF-I axis. However, data have not always been well characterized and were
      sometimes conflicting. The small number of CFS patients investigated in earlier
      studies may have played a role in the interpretation of the results. SUBJECTS AND
      DESIGN: Hormonal testing was performed in 73 nonobese CFS patients and nonobese
      21 age-and gender-matched healthy controls. We investigated GH, ACTH and cortisol
      responses to insulin-induced hypoglycaemia. In a subgroup of patients arginine
      and clonidine stimulation for GH was also performed. Nocturnal secretion of GH,
      ACTH and cortisol were determined. Serum levels of IGF-I, prolactin, TSH, and
      free thyroxine were also measured. Visceral fat mass was assessed by CT scanning.
      RESULTS: GH response to insulin induced hypoglycaemia assessed by peak value
      (17.0 +/- 13.1 microg/l vs. 22. 1 +/- 9.8 microg/l; P = 0.01) and by AUC (450.0
      +/- 361.3 microg/l vs. 672.3 +/- 393.0 microg/l; P = 0.002) was significantly
      decreased in CFS patients vs. controls. Nocturnal GH secretion assessed by GH
      peak value (5.4 +/- 3.7 vs. 9.0 +/- 5.1 microg/l; P = 0.44) and by AUC (34.4 +/-
      20.2 vs. 67.4 +/- 43.1; P = 0.045) was also significantly impaired in CFS
      patients. Arginine and clonidine administration showed no differences in GH
      secretion between CFS patients and controls. In the CFS group, GH peak values
      were significantly higher after ITT than after arginine (P = 0.017) or clonidine
      (P = 0.001). No differences in serum IGF-I levels were found between CFS patients
      and controls. Except for a significantly lower nocturnal cortisol peak value, no
      differences were found in ACTH and cortisol secretion between CFS patients and
      controls. Significantly higher serum prolactin levels (7.4 +/- 4.7 microg/l vs.
      4.4 +/- 1.3 microg/l; P = 0.004) and significantly higher serum TSH levels (1.6
      +/- 1.0 mU/l vs. 1.0 +/- 0.4 mU/l; P = 0.011) were found in CFS patients. Serum
      free thyroxine was comparable in both groups. Visceral fat mass was significantly
      higher in CFS patients (86.6 +/- 34.9 cm2 vs. 51.5 +/- 15.7 cm2; P < 0.001).
      CONCLUSIONS: We observed a significant impairment of GH response during insulin
      induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These
      changes did, however, not lead to different concentrations in serum IGF-I. The
      clinical expression of this inadequate GH secretion can thus be questioned,
      although the alteration in body composition may be related to this relative GH
      deficiency. Significantly increased prolactin and TSH levels were found when
      compared to controls. These findings give support to the hypothesis of a
      decreased dopaminergic tone in CFS. Further investigations are required in order
      to identify specific adaptations within the neurotransmitter system in CFS and to
      determine the clinical importance of the impaired GH homeostasis.

PMID- 10931087
TI  - Low dose (1 microg) ACTH test in the evaluation of adrenal dysfunction in pre
      clinical Addison's disease.
AB  - OBJECTIVE: The presence of 21-hydroxylase autoantibodies (21OHAb) is a marker of
      adrenal autoimmunity and can be used to identify subjects with pre-clinical
      Addison's disease. The low-dose (1 microg) ACTH test (LDT) is more sensitive than
      the high-dose (250 microg) test (HDT) for the diagnosis of pituitary adrenal
      insufficiency, but no information is available on the use of a LDT in subjects
      with autoimmune adrenalitis and primary adrenal insufficiency. The aim of our
      study was to evaluate the clinical use of the LDT in the diagnosis of early
      adrenocortical dysfunction in patients with adrenal autoantibodies. DESIGN AND
      METHODS: Firstly, we evaluated the cortisol responses to both a LDT and a HDT in
      a group of 12 healthy volunteers. We then performed a LDT in 11 subjects positive
      for 21OHAb, but without clinical signs of Addison's disease identified by
      screening 920 patients with one or more organ-specific autoimmune diseases. In
      all cases, the LDT was followed by a sequential HDT which was used as a control
      test of the sensitivity and specificity of the LDT. RESULTS: In healthy subjects,
      the peak cortisol levels after the LDT were similar to those after the classical
      HDT. In 21OHAb-positive subjects, the LDT showed a pathological response in five
      out of 11 (45%) cases and the diagnostic concordance between the results of the
      LDT and those of the HDT was 100%. All the five cases with pathological LDT were
      also positive for adrenal cortex autoantibodies (ACA) and 4/5 had high levels of
      basal ACTH. One subject with pathological LDT developed clinical Addison's
      disease 4 months after the test had been performed. CONCLUSIONS: Our study
      demonstrates that the low dose ACTH test has a high diagnostic sensitivity and
      specificity for primary adrenal insufficiency and suggests that it can accurately
      identify subjects with pre-clinical adrenal dysfunction.

PMID- 10931088
TI  - CYP21 analysis and phenotype/genotype relationship in the screened population of
      the Italian Emilia-Romagna region.
AB  - OBJECTIVES: We have genotyped the patients with congenital adrenal hyperplasia
      due to 21-hydroxylase deficiency identified from March 1980 to December 1997
      through a combined program of neonatal screening and case survey in the Emilia
      Romagna Region (Italy). We have also analysed retrospectively the possible
      advantages of genotypical neonatal classification. DESIGN: A 'phase A' of
      screening and clinical monitoring (March 1980-September 1983 and March 1991
      December 1997) and a 'phase B' of clinical monitoring only (October 1983-February
      1991) were taken into account. PATIENTS: A total of 61 patients (20 salt wasting,
      nine simple virilizing and 32 nonclassical forms) were genotyped, HLA typed and
      hormonally tested to understand better the genotype/phenotype relationship and
      the epidemiology and geographical distribution of associated mutations. The fully
      genotyped patients were classified into four mutation groups according to the
      degree of enzymatic activity ('null' and 'A' to 'C'). RESULT: The most frequent
      genotype alterations were deletion (24.1% classical, 3.3% nonclassical forms),
      large gene conversion (9.2% classical, 1.7% nonclassical forms), In2 splice
      (27.7% classical, 15.0% nonclassical forms), I172N (5.5% classical, 10.0%
      nonclassical forms), V281L (3.7% classical, 43.3% nonclassical forms), P453S
      (5.0% nonclassical forms). A significant difference (chi2 = 5.101; P < 0.025) in
      the distribution of classical genotypes was found in Romagna (south-east;
      incidence 1 : 7437 newborns) compared to Emilia (north-west; incidence 1 : 25 090
      newborns). Two putative new mutations were found in our population. Little
      discrepancy was found between genotype and phenotype. CONCLUSIONS: The high
      frequency of genotypes 'null' or 'A' in the 'phase A' vs. 'phase B' of our study
      confirms the usefulness of neonatal screening in preventing the death of male
      patients with salt wasting forms. The substantial similarity in the mutational
      spectrum of classical forms found in our study, based on the detection of all the
      classical patients of a specific area, leads us to believe that the distribution
      of mutations is due to the inherent characteristics of the gene locus, and that
      regional effects play a minor role. Prompt neonatal genotyping can be of valuable
      diagnostic assistance in neonatal screening for the confirmation of the diagnosis
      in newborns with moderately elevated 17 hydroxyprogesterone levels.

PMID- 10931089
TI  - Prolonged activation of the hypothalamus-pituitary-gonadal axis in a child with X
      linked adrenal hypoplasia congenita.
AB  - X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder of
      the human adrenal cortex that is caused by a mutation of the DAX-1 gene, a member
      of the nuclear hormone receptor superfamily. Hypogonadotrophic hypogonadism is
      frequently associated with this disease and the DAX-1 mutation is known to impair
      gonadotrophin production by acting at both the hypothalamic and pituitary levels.
      However, three recent studies reported that the hypothalamic-pituitary-gonadal
      axis was active in six infants with AHC, suggesting that a difference exists in
      the central regulation of hypothalamic-pituitary-gonadal activity between infant
      boys and pubertal boys. To determine the effect of the DAX-1 gene mutation on the
      axis in early childhood, we measured testosterone, LH, and FSH and performed LH
      releasing hormone tests on a boy with AHC from birth to 3 years of age.
      Surprisingly, our findings showed that the axis was active from the infantile
      period to 3 years of age. This delayed initiation of the prepubertal pause, or
      prolonged activation of the axis, indicates that the DAX-1 gene is related to the
      control mechanism of the prepubertal restraint of gonadotrophin secretion.

PMID- 10931091
TI  - 3rd teupitz colloquium: 'Basic research in endocrine dermatology'

PMID- 10931090
TI  - New breakpoints in both the H4 and RET genes create a variant of PTC-1 in a post
      Chernobyl papillary thyroid carcinoma.
AB  - Two main types of RET/PTC oncogene, named RET/PTC-1 and 3, occur in papillary
      thyroid carcinomas especially in those from Belarus children after the Chernobyl
      nuclear accident. Several variants of RET/PTC-3 have also been found, having
      different break points with respect to the classical RET/PTC-3. To our knowledge,
      no variant of RET/PTC-1 has been described up to now. We found a post-Chernobyl
      papillary thyroid carcinoma with an RET/PTC-1 rearrangement characterized by a
      transcript longer than expected. Sequence analysis of the PCR product obtained
      after RT-PCR revealed new fusion points between H4 and RET genes. The genomic
      sequence showed new breakpoints in both H4 intronic and in RET exonic regions.
      The RET gene breakpoint occurred within exon 11, at variance with the classical
      form of RET/PTC-1, in which it is in intron 11. As a consequence of this new
      fusion point, the transcript included 132 nucleotides of exon 11, coding for 44
      amino acids of RET protein. Regarding the H4 gene, the classical breakpoint is in
      the first intron and the cDNA contains a fragment of 339 nucleotides. In our case
      the cDNA had a longer fragment of H4 involving a total of 1266 nucleotides.
      Sequencing of genomic DNA revealed a rearrangement breakpoint at position 886 of
      a new H4 intron located downstream of the 1266 coding region. Furthermore, as a
      consequence of the activation of a cryptic splicing site, 132 nucleotides of this
      intron were spliced between the H4 and RET genes. Sequence analysis of the new
      chimera showed that the original frames of H4 and RET were joint with the
      intronic sequence without disruption of the open reading frame (ORF). Moreover,
      the genomic DNA of this case showed transforming activity in the DNA-mediated
      transfection assay using NIH-3T3 cells. In conclusion, we describe here the first
      variant of RET/PTC-1 oncogene, which we have termed 'long'-PTC-1, characterized
      by new breakpoints of both genes involved in the rearrangement and having
      transforming activity. Similar to previously reported PTC-3 variants, long-PTC-1
      has been found in a post-Chernobyl papillary thyroid carcinoma confirming that
      RET/PTC rearrangements other than the classical forms (RET/PTC-1 and -3) are
      specifically associated with radiation-induced papillary thyroid cancer.

PMID- 10931092
TI  - Sertoli cell function in the ageing male.

PMID- 10931093
TI  - Serum inhibin B levels in community-dwelling elderly men.
AB  - BACKGROUND AND OBJECTIVE: Ageing in men is accompanied by a decline of Leydig
      cell function, with a 50% decrease of the population means for serum free
      testosterone between age 25 and 75 years. Information on Sertoli cell function
      and spermatogenesis in the elderly is scarce. Studies on seminal parameters in
      ageing men have suggested that spermatogenesis may be fairly well maintained in
      the elderly, but they included mostly selected subjects and only few men over 60
      years. More systematic studies are lacking. The aim of the present study was to
      assess serum inhibin B levels in elderly men as an index of global Sertoli cell
      function and spermatogenic activity. SUBJECTS AND MEASUREMENTS: Specific
      immunoassays were used to determine serum levels of inhibin B, gonadotrophins,
      testosterone and oestradiol in blood obtained between 0800 and 1000 h. from 189
      ambulatory, community-dwelling elderly men (age: 70-85 years) and, for
      comparison, from 51 middle-aged (35-54 years) and 50 young (< 35 years) controls.
      RESULTS: All age groups combined, serum inhibin B was only weakly negatively
      correlated to age (Spearman correlation coefficient: - 0.17; P < 0.01) and more
      strongly to serum FSH (- 0. 52; P < 0.001). In a multiple regression analysis
      serum FSH, but not age or serum free testosterone, emerged as an independent
      determinant of serum inhibin B levels. An age-related decline of median inhibin B
      levels in the study population was essentially limited to the younger age groups,
      with stable levels between age 35 and 79 years, and only a modest further
      decrease thereafter. There was a progressive age-related increase of serum FSH
      across age groups with, consequently, a marked decrease of the serum inhibin B :
      FSH ratio. The prevalence of men presenting with low serum inhibin B (below 10th
      percentile for inhibin B levels in men < 35 years), indicative of deficient
      Sertoli cell function and spermatogenesis, increased most strikingly between men
      < 35 years and those 35-54 years, which contrasts with the more progressive
      increase at an older age of the prevalence of low serum (free) testosterone.
      CONCLUSION: Global testicular Sertoli cell function and spermatogenic activity,
      as assessed indirectly through serum inhibin B levels, appear to be well
      maintained in ambulatory elderly men, albeit there are age-related alterations at
      the level of the Sertoli cells as indicated by a progressive increase of
      testicular drive by pituitary FSH.

PMID- 10931094
TI  - Inhibins A and B are regulated differentially in the early post-partum period.
AB  - BACKGROUND: The early postpartum period is characterized endocrinologically by a
      rapid fall in the levels of oestradiol (E2) and immunoreactive inhibin, and a
      delayed rise in serum follicle stimulating hormone (FSH). No description is
      currently available of changes in serum inhibins A and B. OBJECTIVES: The present
      study aimed to examine the levels of inhibin A and B during the early weeks of
      postpartum lactational amenorrhoea, to determine whether there was evidence for
      differential regulation of the two hormones at a time when no dominant follicle
      was developing in the ovary. SUBJECTS AND METHODS: Serum samples were available
      from 12 subjects aged 29-38 in whom postpartum levels of FSH, immunoreactive
      inhibin, E2 and prolactin had been examined previously. Samples for hormone
      assays had been obtained prior to delivery, daily for the 3-5 days postpartum,
      and weekly thereafter. Inhibins A and B were measured by specific ELISA assays,
      and results were calculated as 10 day averages for samples obtained on days 1-10,
      11-20, 21-30, etc. postpartum. Normal hormone concentrations for reference were
      obtained from volunteers, also aged 29-38, sampled on days 3-5 of a normal
      menstrual cycle. RESULTS: Inhibin A in the predelivery sample ranged from 62 to
      1243 ng/l, geometric mean 592. Concentrations fell rapidly postpartum and reached
      a nadir in the low follicular phase range between days 5 and 37 postdelivery,
      mean 13.6 days. The concentrations of both inhibin B and FSH rose 14-27 days
      postpartum from their initially low postdelivery levels, to reach the normal
      follicular phase range. These increases in concentration were significantly
      correlated in all individual subjects. CONCLUSIONS: The secretion of inhibin A
      and B is regulated differentially during the early stages of lactational
      amenorrhoea, just as it is in the late luteal phase of the normal menstrual
      cycle. Whilst inhibin A falls postpartum, reflecting cessation of placental
      function, and remains low until ovulatory cycles are resumed, FSH and inhibin B
      rise after a delay of two weeks or more. It is postulated that the rise of
      inhibin B is the result of secretion from a cohort of small follicles stimulated
      by rising FSH levels.

PMID- 10931095
TI  - Reverse transcriptase is elevated in the thyroid tissue from Graves' disease
      patients.
AB  - OBJECTIVE: Hypertrophy of the thyroid gland in Graves' disease is related to an
      autoimmune response directed against TSH receptors found in thyroid cells.
      Recently, investigators have suggested that autoimmune diseases, including
      thyroid diseases may, at least in part, correlate with the expression of proteins
      encoded by the retroviral genome. In the present study, to confirm the
      correlation between thyroid autoimmune disorders and retroviral infections, we
      examined reverse transcriptase (RT) activity in thyroid tissues as a marker of
      retroviral infection. PATIENTS AND MEASUREMENTS: Thyroid tissues obtained at
      surgery from patients with various thyroid disorders (normal thyroid adjacent to
      adenoma, six cases; Graves' disease thyroid tissue, 25 cases; adenoma, eight
      cases; papillary carcinoma, 12 cases; Graves' disease peripheral blood
      lymphocytes, 11 cases) were used for RT assay, using a specific, improved assay
      system. RESULTS: Thyroid tissue extracts from patients with Graves' disease
      contained high RT activity which resembled that demonstrated in retroviruses. The
      RT existed in the thyroid tissue as a complex, with endogenous template RNA, and
      the activity was confirmed not to be due to other DNA polymerases. CONCLUSION:
      Retroviral RT distinguished from known cellular DNA polymerases is expressed in
      the thyroids of patients with Graves' disease. In a permissive genetice and
      immunological environment, retroviral DNA integrated into genomic DNA could
      precipitate the onset of Graves' disease.

PMID- 10931096
TI  - Thyroperoxidase (TPO) immunostaining of the solitary cold thyroid nodule.
AB  - OBJECTIVE: To evaluate the value of immunostaining using the monoclonal antibody
      (MoAB47) against thyroperoxidase (TPO) in distinguishing between benign and
      malignant tumour cells in fine needle aspiration cytology (FNAC) samples obtained
      from a solitary cold nodule of the thyroid gland for the purpose of strengthening
      the indication for thyroid surgery. DESIGN: A prospective, immunocytochemical
      study of FNACs taken from patients with solitary cold thyroid nodules who
      presented to Rigshospitalet, Copenhagen, Denmark, during the period April 1993 to
      May 1996. The first sample series was taken perioperatively in order to test the
      utility of the method. In the second part of the study samples were obtained
      preoperatively by ultrasonic guided aspiration. Tissue sections from the nodules
      obtained during a subsequent operation served as controls. PATIENTS: One hundred
      and eighty-one patients, 150 women and 31 men, were studied. The age range was 14
      89 years with a median age of 44 years. Fifty-seven patients were excluded from
      the study for various reasons leaving us with a total of 124 nodules from 124
      patients for final evaluation. METHODS: FNAC cells and corresponding nodular
      tissue were stained by immunocyto- and immuno-histochemistry using MoAb47 and by
      routine staining methods. Samples were considered benign if 80% or more of the
      epithelial-looking cells of both the FNACs and the histological tissue sections
      of the nodule were stained by TPO. Consequently, samples were considered
      malignant if more than 20% of the epithelial-looking cells failed to stain for
      TPO. Routinely stained tissue cells and sections served as diagnostic controls.
      RESULTS: A pattern with negative TPO staining was found in all lesions which, by
      conventional histological staining, were subsequently proven to be malignant. A
      universal and reliable, positive TPO staining pattern was found in all
      subsequently proven benign lesions, with the exception of one out of 26
      follicular adenomas. This gave the method a sensitivity of 1.0 (negative TPO
      staining = malignancy in 27 out of 27) and a specificity of 0.99 (positive TPO
      staining = benign lesion, in 96 out of 97). Positive and negative predictive
      values were 0.96 and 1.00 respectively. CONCLUSION: Thyroperoxidase
      immunostaining of fine needle aspirates from solitary, scintigraphically cold
      nodules of the thyroid gland has proved to be an important and reliable
      diagnostic tool for distinguishing between benign and malignant nodules. Thus,
      patients might be spared further surgery if not otherwise indicated.

PMID- 10931097
TI  - Low birth weight is not associated with clinically overt thyroid disease: a
      population based twin case-control study.
AB  - OBJECTIVE: In recent years low birth weight has been proposed as a risk factor
      for the development of several chronic diseases in adult life, including diabetes
      and subclinical autoimmune thyroid disease. The association could, however, also
      be due to genetic or environmental factors affecting both birth weight and
      adverse health outcomes in adult life. Moreover, it is at present unknown whether
      or not low birth weight is associated with an increased risk of developing
      clinically overt thyroid disease. The aim of the present study was to investigate
      the impact of birth weight and several other birth characteristics on the
      development of clinically overt thyroid disease. DESIGN: A twin case-control
      study of same sex twin pairs. PATIENTS: One hundred and thirty-one same sex twin
      pairs (262 twin individuals) discordant for clinically overt thyroid disease,
      ascertained from a population based nation-wide twin register. MEASUREMENTS:
      Information about birth weight, birth length, birth order (first vs. second
      born), and prematurity was obtained from the original midwife records. RESULTS:
      Forty-nine twin pairs were discordant for clinically overt autoimmune thyroid
      disease (Graves' disease = 35 and Hashimoto's thyroiditis = 14) and 82 pairs were
      discordant for overt nonautoimmune thyroid disease (Simple goitre = 79 and toxic
      nodular goitre = 3). Overall, there was no difference in birth weights between
      probands and the healthy co-twins in monozygotic (MZ, n = 39) or in dizygotic
      (DZ, n = 92) pairs (MZ: mean +/- SE: 2619 +/- 93 g vs. 2553 +/- 89 g, P = 0.40;
      DZ: 2576 +/- 45 g vs. 2585 +/- 49, P = 0.86). By means of logistic regression,
      the impact of other birth characteristics such as birth length, birth order
      (first vs. second born), and prematurity was tested. None of the variables
      reached statistical significance. Subdividing the twin pairs into those
      discordant for clinically overt Graves' disease, Hashimoto's thyroiditis, and
      nonautoimmune thyroid disease did not change the results. CONCLUSIONS: This is
      the first study of the effect of birth weight and other birth characteristics on
      the subsequent development of clinically overt thyroid disease in which maternal,
      socioeconomic, and to a high degree, genetic factors have been controlled for.
      Our study did not show any effect of birth weight or any of the other birth
      characteristics on the risk of developing clinically overt autoimmune or
      nonautoimmune thyroid disease.

PMID- 10931098
TI  - Thyroid function in wholly breast-feeding infants whose mothers take high doses
      of propylthiouracil.
AB  - BACKGROUND: Propylthiouracil (PTU) might theoretically be preferred over
      methimazole (MMI) during breast-feeding because of its lower milk/serum
      concentration ratio (0.1 vs. 1.0). The problem is that Graves' disease often
      relapses during the postpartum period, and high doses of PTU are sometimes needed
      to control maternal hyperthyroidism) during breast-feeding. However, there are
      virtually no data on the effects of maternal PTU on thyroid status of infants
      whose mothers take more than 300 mg PTU daily and who are wholly breast-feeding.
      OBJECTIVES: To investigate whether mothers can breast-feed without adverse
      effects on infants' thyroid status while taking 300 mg or more daily of PTU.
      SUBJECTS AND DESIGN: Eleven infants who were wholly breast-fed while their
      mothers took PTU 300-750 mg daily for Graves' hyperthyroidism were included in
      this study. In one of the 11 infants, the mother also took iodine 6 mg daily for
      a limited period. Thyroid status in these infants was evaluated. MEASUREMENTS:
      Free T4 (FT4), thyrotrophin (TSH), and TSH binding inhibiting antibody (TBIAb)
      concentrations were examined at least once in the age range 6 days to 9 months.
      Maternal blood was also examined for FT4 and TBIAb on the same day, or within a
      week, of the infants' blood tests. FT4, TSH and TBIAb concentrations at birth
      were examined, using cord blood, in cases where antithyroid drugs had been
      continued through delivery. RESULTS: Three of the 11 infants had TSH
      concentrations higher than the normal range for adults. In one of the three
      infants, the TSH concentration, which was determined 19 weeks after birth, was
      just above the normal range. In the remaining two infants whose mothers had taken
      PTU through delivery, TSH concentrations, determined within 7 days after birth,
      were distinctly high, but they became normal while maternal PTU doses were the
      same as or higher than those at the initial examination. Maternal PTU doses or
      FT4 concentrations were not significantly correlated with infants' TSH
      concentrations. CONCLUSION: Mothers can breast-feed while taking propylthiouracil
      at doses as high as 750 mg daily without adverse effects on thyroid status in
      their infants.

PMID- 10931099
TI  - Changes in serum thyroid hormones levels and their mechanisms during long-term
      growth hormone (GH) replacement therapy in GH deficient children.
AB  - OBJECTIVE: The effects of GH therapy on thyroid function among previous reports
      have shown remarkable discrepancies, probably due to differences in hormone assay
      methods, degree of purification of former pituitary-derived GH preparations,
      dosage schedules, diagnostic criteria, patient selection, duration of treatment
      and study design. These considerations motivated us to investigate whether and
      how GH replacement therapy changes serum thyroid hormone levels, including the
      much less studied rT3 levels, in a group of unequivocally GH-deficient children
      receiving long-term recombinant human GH therapy. PATIENTS AND DESIGN: Twenty
      clinically and biochemically euthyroid children were studied in two therapeutic
      conditions: on GH replacement therapy for at least 6 months and without GH
      replacement, either before GH was started or after GH was withdrawn for 30-60
      days. Eight patients were on thyroxine replacement treatment and thyroxine doses
      were kept constant during the study. Blood was collected before and after 15, 20
      and 60 minutes of TRH administration in both therapeutic conditions (with GH and
      without GH). MEASUREMENTS: Concentrations of thyroid hormone levels were
      determined only in sera obtained before TRH administration. FT4, T3 and TSH were
      measured by immunoflourimetric assays and rT2 was measured by immunoradioassay.
      RESULTS: Patients were classified into two groups, according to basal TSH levels:
      group I (TSH > 0.4 mU/l, n = 12) and group II (on thyroxine and TSH < 0.05 mU/l,
      n = 8). In both groups, serum FT4 levels decreased (17. 0 +/- 1.1 vs. 14.3 +/-
      0.9 mU/l, P < 0.001, and 18.0 +/- 1.7 vs. 14. 2 +/- 1.7 mU/l, P < 0.01,
      respectively), serum T3 levels increased (1.8 +/- 0.1 vs. 2.4 +/- 0.2 nmol/l, P <
      0.001, and 1.9 +/- 0.3 vs. 2.4 +/- 0.2 nmol/l, P < 0.05, respectively), and serum
      rT3 levels decreased (0.35 +/- 0.03 vs. 0.25 +/- 0.03 nmol/l, P < 0.01, and 0. 48
      +/- 0.06 vs. 0.34 +/- 0.06 nmol/l, P < 0.01, respectively). Basal (3.2 +/- 0.50
      vs. 2.6 +/- 0.72 mU/l, P = 0.28, paired t-test), TRH-stimulated peak TSH levels
      (13.9 +/- 5.3 vs. 15.9 +/- 8.0 mU/l, P = 0.35, paired t-test) and TRH-stimulated
      TSH secretion, expressed as area under the curve (609 +/- 97 vs. 499 +/- 53
      mU/l.minutes-1, P = 0.15, paired t-test), remained unchanged during GH
      replacement in group I patients. Low serum FT4 and high serum T3 levels were
      observed in only one patient each, but low serum rT3 levels were found in six
      patients (four in group I and two in group II) during GH replacement.
      CONCLUSIONS: These results show that long-term GH replacement therapy in children
      with unequivocal GHD significantly decreases serum FT4 and rT3 levels and
      increases serum T3 levels; that these changes are independent of TSH and result
      from increased peripheral conversion of T4 to T3 and that GH replacement therapy
      in GH deficient children does not induce hypothyroidism, but simply reveals
      previously unrecognized cases whose serum FT4 values fall in the low range during
      GH replacement.

PMID- 10931100
TI  - Cranial radiotherapy of childhood brain tumours: growth hormone deficiency and
      its relation to the biological effective dose of irradiation in a large
      population based study.
AB  - OBJECTIVE: The study was to determine the incidence of GH deficiency (GHD)
      following cranial radiotherapy (RT) for a childhood brain tumour in a large
      population based study and analyse the biological effective dose (BED) to the
      hypothalamus/pituitary (HP) region as a risk factor. DESIGN: BED was assessed by
      use of the linear-quadratic (LQ) model, which gives a means of expressing the
      biological effect of various treatment schedules in a uniform way. In patients
      aged >/= 18 years (n = 53) GH status was assessed by an insulin-tolerance test
      (ITT) (n = 34), however, in patients with seizure disorders (n = 19), and in 20
      children aged < 18 years GH status was assessed by an arginine test. Cut-off
      levels for GHD, indicating GH substitution, were defined by a peak GH response of
      < 9 mU/l and < 15 mU/l for patients >/= 18 and < 18 years, respectively.
      PATIENTS: Ninety-one children aged < 15 years eligible for the study, diagnosed
      between 1970 and 1997 in the Eastern part of Denmark, the Faroe Islands and
      Greenland, with a primary brain tumour not directly involving the HP axis. 84% (n
      = 76) agreed to participate. Three patients were excluded due to hypothyroidism
      detected at time of testing. MEASUREMENTS: Serum GH and levels of serum insulin
      like growth factor-I (s-IGF-I) and serum insulin-like growth factor binding
      protein-3 (s-IGFBP-3) were measured. BED was assessed to the HP region. RESULTS:
      The median age at the time of RT was 8.7 years (range: 0.8-14.9 years) and the
      median time of follow-up was 15 years (range: 2-28 years). Fifty-eight patients
      (80%) had GHD and they had received a median BED of 77.5 Gy to the HP region,
      whereas the median BED was 54.5 Gy for 15 patients without GHD (P = 0.002). Peak
      GH and BED were correlated (rs = -0.53, P < 0001). Median IGF-I SDS and IGFBP-3
      SDS were -2.5 (-5.2-0.7 SDS) and -1.7 (-5.8-0.9 SDS), respectively, and IGF-I SDS
      was correlated to peak GH (rs = 0.45, P < 0.001). Peak GH and length of follow-up
      were related (rs = -0.28, P = 0.018). Stepwise backward multiple linear
      regression analysis showed that the best-fit model to predict the peak GH release
      following ITT/arginine stimulation included BED (P < 0.0001) and length of follow
      up (P = 0.05). CONCLUSIONS: The data of this study suggest that the majority of
      long-term survivors of brain tumours develop GH deficiency following radiotherapy
      in childhood and that the adverse effects of radiotherapy may be directly related
      to the biologically effective dose. With longer follow-up fewer patients might
      respond normally to GH stimulation tests.

PMID- 10931101
TI  - Establishment of reference values for standard dose short synacthen test (250
      microgram), low dose short synacthen test (1 microgram) and insulin tolerance
      test for assessment of the hypothalamo-pituitary-adrenal axis in normal subjects.
AB  - OBJECTIVE: To assess the integrity of the hypothalamo-pituitary-adrenal(HPA)
      axis, many authors have proposed the short synacthen test (ACTH1-24,
      Tetracosactrin) as a replacement for the insulin tolerance test (ITT). The aim of
      this study was to compare the plasma cortisol response obtained with both short
      synacthen tests (high dose (HDT, 250 microgram) and low dose (LDT, 1 microgram))
      with the peak reached during the ITT in healthy volunteers, and to establish the
      plasma cortisol cut-off level in each test. SUBJECTS AND METHODS: Thirty healthy
      subjects (16 F, 14 M), mean age 34 years, underwent both short synacthen tests.
      Twenty healthy subjects, 15 of whom (11 F, nine M) belonged to the above group,
      mean age 30 years, underwent an ITT. Plasma cortisol was measured using a
      chemiluminiscence immunoassay. RESULTS: There were no differences between plasma
      cortisol 30 minutes after both short synacthen tests (HDT: 684 +/- 123, LDT: 669
      +/- 119 nmol/l) and the peaks reached with the LDT (691 +/- 123 nmol/l) and the
      ITT (673 +/- 99 nmol/l). The only difference (P < 0.001) was found in the
      comparison of plasma cortisol peak reached with the HDT (802 +/- 142 nmol/l) with
      the other tests. Plasma cortisol levels obtained in the 5th percentile in each
      test were: at + 30 minutes: (HDT: 537, LDT: 489 nmol/l), peak: (HDT 649, LDT 498,
      ITT: 539 nmol/l). CONCLUSIONS: Comparison of the plasma cortisol response at + 30
      minutes with both short ACTH tests and the peak in the insulin tolerance test did
      not reveal differences. Each test, for each time point and for each biochemical
      method, requires its own minimum threshold of normality to assess the hypothalamo
      pituitary-adrenal axis.

PMID- 10931102
TI  - Phenotype and phenocopy: the relationship between genotype and clinical phenotype
      in a single large family with multiple endocrine neoplasia type 1 (MEN 1).
AB  - BACKGROUND: The majority of reports describing the natural history and prognosis
      of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than
      molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND
      PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst
      152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom
      a determination of MEN 1 status had previously been made by phenotype screening.
      The predictive utility of both clinical and molecular screening techniques are
      described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected
      members of this family. Seven (10%) of 71 individuals satisfying clinical
      diagnostic criteria for MEN 1 were found to be genetically negative (excluded by
      mutation analysis and haplotyping) for MEN 1. These cases of MEN 1 phenocopy
      comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary
      adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of
      the patients with hyperparathyroidism had previously required parathyroidectomy
      and each had achieved normocalcaemia following parathyroid resection. Predictive
      genetic testing prospectively identified three children with the MEN 1 genotype.
      Serum calcium was normal at the time of their initial molecular genetic
      diagnosis. In each case hyperparathyroidism subsequently developed during
      adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an
      important differential diagnosis in patients exhibiting an multiple endocrine
      neoplasia type 1 phenotype. This is a relevant consideration, particularly when
      the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but
      nonspecific, criteria such as mild hyperparathyroidism, pituitary micoadenoma,
      and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to
      confirm clinical diagnoses of multiple endocrine neoplasia type 1.

PMID- 10931103
TI  - Alterations of the 11p15 imprinted region and the IGFs system in a case of
      recurrent non-islet-cell tumour hypoglycaemia (NICTH).
AB  - BACKGROUND AND OBJECTIVE: Non-islet-cell tumour hypoglycaemia (NICTH) is a rare
      disorder and has been explained by oversecretion of non mature IGF-II and
      dysregulation of the IGFs sytem. The mechanisms responsible for tumoural IGF-II
      overexpression in NICTH have been rarely studied. We report an extensive study of
      IGF-II and IGFBPs as well as chromosome 11p15 gene expression regulation in a
      case of a pleural fibrosarcoma in a 63-year-old patient presenting with NICTH.
      METHODS AND RESULTS: Abnormal high molecular weight precusor forms of IGF-II were
      present in the patient's serum and were associated with dramatic alterations in
      the circulating levels of IGF-I, IGF-II and their binding proteins, as well as an
      inhibition of the somatotroph axis. These alterations returned to normal
      following complete surgical removal of the tumour. No structural change in
      chromosome 11p15 region was apparent in the tumour. However, dysregulation of
      this imprinted region was demonstrated, leading to the loss of imprinting of the
      IGF-II gene associated with high IGF-II expression, and by contrast decreased
      level of expression of H19 and p57KIP2 genes. Recurrence of the tumour four years
      latter was not associated with hypoglycaemia or changes in the levels of
      circulating IGFs or IGFBPs, despite IGF-II overexpression by the tumour. This
      suggests that a large tumour volume is required to reach high enough levels to
      cause changes in the levels of circulating IGFs and IGFBPs, and to cause
      hypoglycaemia. CONCLUSION: These results suggest that a dysregulation of gene
      expression and imprinting of chromosome 11p15 region is associated with tumour
      growth and IGF-II overexpression in non-islet-cell tumour hypoglycaemia.

PMID- 10931104
TI  - The low dose ACTH stimulation test is less sensitive than the overnight
      metyrapone test for the diagnosis of secondary hypoadrenalism.
AB  - OBJECTIVE: The 1 microgram ACTH stimulation test has been advocated as a
      sensitive indicator of the integrity of the hypothalamic-pituitary-adrenal axis
      in patients with suspected hypopituitarism. The aim of our study was to define
      the normal response to 1 microgram ACTH stimulation in a control population and
      to study the sensitivity and specificity of the test in a group of patients with
      suspected pituitary disease. DESIGN: A prospective analysis of the performance of
      the 1 microgram ACTH stimulation test in a group of patients with pituitary
      disease. PATIENTS: The cortisol response to 1 microgram ACTH was evaluated in 21
      normal subjects and 65 patients with pituitary disease. The patients with
      pituitary disease were divided into two groups according to the 11-deoxycortisol
      response to overnight metyrapone: normal (11-deoxycortisol > 200 nmol/l) and
      subnormal ACTH secretory status (11-deoxycortisol < 200 nmol/l). MEASUREMENTS: In
      both controls and patients, blood was sampled for cortisol at - 15, 0, + 20, +
      30, + 40 and + 60 minutes after intravenous administration of 1 microgram
      synthetic ACTH (Synacthen(R)). The overnight metyrapone test was performed only
      in the subjects with pituitary disease. Metyrapone (30 mg/kg) was administered
      orally at 2300 h and blood was sampled at 0830 h the following morning for 11
      deoxycortisol. RESULTS: The 65 patients with pituitary disease were categorized
      according to the 11-deoxycortisol response to metyrapone as follows: 53 normal
      (11-deoxycortisol > 200 nmol/l) and 12 subnormal (< 200 nmol/l). The 12 patients
      who failed the metyrapone test had a significantly impaired cortisol response to
      low dose ACTH stimulation at all time points when compared with both the control
      group and the pituitary patients with a normal response to metyrapone (P <
      0.001). Comparing the pituitary patients who had a normal response to metyrapone
      and the control subjects, there was no significant difference in the cortisol
      response to ACTH (P > 0.05). The minimum cortisol response at 30 minutes in the
      21 control subjects was 414 nmol/l and this was defined as the minimum normal
      cortisol response to 1 microg ACTH. Using this criterion, six of the 12 patients
      with a subnormal response to metyrapone had a normal cortisol response to low
      dose ACTH stimulation. Empirically increasing the cortisol cut-off to 600 nmol/l
      increased the sensitivity of the low dose ACTH test to 83%, although the
      specificity was reduced from 100% to only 58%. CONCLUSIONS: The normal cortisol
      response to low dose ACTH stimulation in 50% of the patients with ACTH deficiency
      proven on metyrapone testing suggests that the 1 microgram ACTH stimulation test,
      like the 250 microgram-test, lacks sensitivity for the diagnosis of ACTH
      deficiency.

PMID- 10931105
TI  - Effects of successful parathyroidectomy on altered arterial reactivity in
      patients with hypercalcaemia: results of a 3-year follow-up study.
AB  - OBJECTIVE: Serum calcium was found to be an independent, prospective risk factor
      for myocardial infarction. We have previously shown that altered arterial
      reactivity in the course of primary hyperparathyroidism, a disease characterized
      by hypercalcaemia, may predominantly involve the arterial media and not the
      endothelium as observed in patients with various stages of atherosclerosis. The
      present study was performed to test whether successful parathyroidectomy can
      improve vascular reactivity in patients with primary hyperparathyroidism.
      SUBJECTS AND DESIGN: Endothelium-dependent, flow-mediated and endothelium
      independent, nitroglycerin-induced dilatation were assessed by brachial artery
      ultrasound (7 MHz) in 18 patients with primary hyperparathyroidism (mean +/- SD;
      age, 55.1 +/- 12.6) prior to and 3 years after successful parathyroidectomy.
      RESULTS: Parathyroidectomy resulted in significant decreases of PTH (242 +/- 186
      vs. 34 +/- 24 ng/l, P = 0. 0001) and serum calcium levels (2.8 +/- 0.3 vs. 2.4 +/
      0.1 mm/l, P = 0.00001) and in an increase of serum phosphate levels (0.78 +/- 0.
      23 vs. 1.17 +/- 0.18 mm/l, P = 0.00001). However, normalization of hormone and
      electrolyte levels did not lead to an improvement of flow-mediated dilatation
      (12.1 +/- 3.1 vs. 11.0 +/- 5.4&, P = 0.49) or nitroglycerin-induced dilatation
      (12.5 +/- 3.1 vs. 13.2 +/- 6.8%, P = 0.68) within the follow-up period. No
      changes were observed with respect to the risk factor profile, vessel size and
      blood flow. CONCLUSION: These data suggest that restoration of normocalcaemia by
      parathyroidectomy cannot improve vascular reactivity in patients with primary
      hyperparathyroidism but may prevent further progression of vascular disease
      within this period of time.

PMID- 10931106
TI  - Urine calcium and urine sodium concentrations are not related, after adjustment
      for urine magnesium.
AB  - BACKGROUND AND OBJECTIVES: Urine calcium correlates with urine sodium. The aims
      of this study were to investigate whether the urine sodium-calcium relationship
      persists into old age and whether it holds after adjustment for urine magnesium.
      DESIGN: Cross-sectional descriptive analysis. PATIENTS: Residents of two aged
      care institutions (median age 84 years) who were not taking diuretics, calcium or
      vitamin D supplements. MEASUREMENTS: Early morning urine calcium, sodium and
      magnesium, plasma creatinine and serum 25-hydroxyvitamin D and parathyroid
      hormone. RESULTS: Urine calcium correlated with urine sodium (r = 0.29, P < 0.01)
      and with urine magnesium (r = 0.56, P < 0.001). After adjustment for urine
      magnesium, the relationship between urine sodium and urine calcium was no longer
      significant. Forty-five percent of the interindividual variation in urine calcium
      was explained by a linear model on the basis of urine magnesium and plasma
      creatinine. CONCLUSION: The data indicate that a correlation between urine sodium
      and calcium persists in very old age. However, this correlation no longer holds
      after adjustment for urine magnesium. Further studies examining urine calcium
      excretion should also consider urine magnesium.

PMID- 10931107
TI  - A case of adrenocortical carcinoma associated with recurrence after laparoscopic
      surgery.
AB  - Laparoscopic adrenalectomy has become increasingly popular because of its
      minimally invasive nature, but guidelines for selection of cases suitable for
      this surgical procedure have not been established. We report a 52-year-old woman
      with adrenocortical carcinoma, manifesting as Cushing's syndrome, treated with
      laparoscopic adrenalectomy. The tumour was removed in toto and had been
      histologically diagnosed as adrenocortical adenoma. However, the patient
      developed intra-abdominal peritoneal dissemination of carcinoma 15 months after
      surgery. Review of the histopathological findings of the resected adrenocortical
      tumour revealed that the neoplasm met five out of nine histological criteria for
      adrenocortical malignancy, and was diagnosed as adrenocortical carcinoma.
      Histopathological examination of the tumour was also consistent with
      adrenocortical carcinoma. The patient responded extremely well to chemotherapy,
      including carboplatin, etoposide and o,p'-DDD (1,1
      dichlorodiphenyldichloroethane), and a subsequent CT (computed tomography) scan
      12 months after the start of chemotherapy demonstrated no evidence of disease.
      However, the patient developed neurological impairment, including dysarthria, as
      a side-effect of o, p'-DDD. The patient died of aspiration pneumonia due to a
      decreased pharyngeal reflex. Postmortem examination revealed no foci of residual
      carcinoma. This case report emphasizes the importance of excluing possible
      adrenocortical malignancy in patients considered for laparoscopic adrenalectomy,
      histopathological diagnosis of adrenocortical malignancy and careful monitoring
      for neurotoxicity during o,p'-DDD treatment.

PMID- 10931108
TI  - X-linked congenital adrenal hypoplasia: new mutations and long-term follow-up in
      three patients.
AB  - Mutations of the DAX-1 gene, which encodes a newly discovered member of the
      nuclear hormone receptor family, were reported to cause X-linked congenital
      adrenal hypoplasia and hypogonadotrophic hypogonadism. While genetic data on DAX
      1 are accumulating, information on the clinical course of the disorder are
      scarce. Here we present a detailed documentation of longitudinal data relating to
      three cases. We retrospectively collected clinical data on three boys (6, 14 and
      14.5 years old) who we examined over a period ranging between 5 and 14 years.
      Mutational analysis of the DAX-1 gene was performed by means of direct sequencing
      of PCR products. The patients presented at ages between 4 and 6 weeks with salt
      wasting, but there was no evidence of hypoglycaemia. All three cases were
      initially erroneously diagnosed with isolated aldosterone deficiency.
      Glucocorticoid deficiency was established by means of ACTH stimulation tests at 4
      months, 3 and 13 years of age. One boy, whose therapy was discontinued at the age
      of 4 months, developed normally until adrenal crisis occurred at the age of 13
      years. In all three cases, congenital hypogonadism was ruled out during infancy,
      as penis size was normal, the testes were descended, and serum samples contained
      normal testosterone levels. One boy exhibited transient hypergonadotrophism at
      age 9 but showed no clinical signs of puberty or an increase in serum
      testosterone. Onset of puberty and LHRH tests proved to be normal in his case as
      well as in another patient studied. In two patients, genetic analysis revealed
      new mutations at the C-terminus of DAX-1, these being a 1-base deletion (656delG)
      inherited from the mother and a de-novo 2-base insertion (728insCA) of the DAX-1
      gene, respectively, both causing frame shift and premature stops at codons 263
      and 398. One boy was affected by a new nonsense mutation of codon 39 (W39X)
      inherited from his mother. Mineralocorticoid deficiency preceded glucocorticoid
      deficiency which could be diagnosed through ACTH stimulation after the neonatal
      period. Transitory functional recovery of the adrenal glands can occur in adrenal
      hypoplasia congenita (AHC). Transient hypergonadotrophism may be one of the first
      indicators of defects in the gonadal axis, although normal initiation of puberty
      is not rare. The definitive diagnosis was established by means of molecular
      analysis of the DAX-1 gene. There was no correlation between types of mutations
      and phenotypes. The diagnostic procedure in male children and adolescents
      presenting with adrenal crisis should include ACTH stimulation tests and
      mutational analysis of DAX-1 in the absence of another proven aetiology.

PMID- 10931109
TI  - Pregnancy in persistent acromegaly.

PMID- 10931110
TI  - Human cultured mast cells.

PMID- 10931111
TI  - The significance of enzymic and other biological activities of proteins in
      relation to their capacity to serve as allergens.

PMID- 10931112
TI  - Stress-induced asthma: a review of research and potential mechanisms.

PMID- 10931113
TI  - Pollution effects on asthmatic children in Europe, the PEACE study.

PMID- 10931114
TI  - Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with
      rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a
      French population.
AB  - BACKGROUND: Bet v 1, the major allergen in birch pollen, is recognized by more
      than 90% of patients allergic to birch in northern and central Europe.
      Immunotherapy is commonly performed with birch pollen extracts. Recently,
      hypoallergenic derivatives of Bet v 1 (rBet v 1 fragments, rBet v 1 dimer and
      trimer) were constructed and purified. OBJECTIVE: Our aim was to compare the
      allergenic activity of wild-type rBet v 1 with recombinant Bet v 1 derivatives
      (rBet v 1 fragments, dimer and trimer) with potentially reduced anaphylactic
      activity by skin testing in a French population. METHODS: Among the 36 birch
      pollen allergic patients included in the study, 29 were tested by skin prick
      testing and 30 by intradermal injections with purified monosubstances: rBet v 1
      fragments (F1: aa1-74 and F2: aa75-160), Bet v 1 dimer and trimer. Intradermal
      tests were performed by the end-point intradermal titration method. Eight of the
      intradermally-tested patients were previously hyposensitized. Tests were
      performed over a period of 6 months (before, during and after birch pollen
      season); Bet v 1-specific IgE and IgG4 subclass responses were measured by
      immunoblotting and ELISA. RESULTS: All patients showed lower reactivity with the
      modified rBet v 1 allergens, both in skin prick and intradermal tests. In 25 and
      23 out of 29 patients the lowest concentration of fragment 1 and 2, respectively,
      resulting in a positive prick test was 100-fold higher than the lowest
      concentration of monomer resulting in a positive prick test. For dimer it was 100
      fold or more in 25 out of 29 patients, and for trimer it was 100-fold or superior
      in 26 out of 29 patients. By intradermal testing, the end-point concentration was
      160-fold higher for trimer than for monomer in 24 patients and 40-fold higher in
      five patients. For the two fragments the end-point concentration was 160-fold
      higher in 20 out of 22 patients. CONCLUSION: Genetically modified hypoallergenic
      derivatives of the major birch pollen allergen, Bet v 1 showed reduced capacity
      to induce immediate type skin reactions. They may represent candidate molecules
      for immunotherapy of birch pollen allergy with reduced risk of anaphylactic side
      effects.

PMID- 10931115
TI  - The 18-kDa form of cat allergen Felis domesticus 1 (Fel d 1) is associated with
      gelatin- and fibronectin-degrading activity.
AB  - BACKGROUND: Fel d 1, an important allergen from domestic cats, is a significant
      cause of asthma. In addition to directly promoting IgE synthesis, other
      biological activities of allergens may contribute to either allergic
      sensitization or the magnitude of allergic effector responses. For example,
      allergens that degrade proteins have been suggested to facilitate allergen
      presentation by increasing parallelular permeability of airways epithelium.
      However, little information exists to indicate whether Fel d 1 has other
      activities relevant to allergic responses. OBJECTIVE: To study whether Fel d 1 is
      associated with enzyme activity. METHODS: Fel d 1 was obtained by a rigorous
      purification strategy and its identity confirmed by laser desorption mass
      spectrometry, cleavage and sequencing. The ability of Fel d 1 to degrade gelatin,
      fibronectin and the artificial substrate N-benzoyl-FVR-p-nitroanilide was
      studied. The effect of Fel d 1 on the morphology of tight junctions in epithelial
      cell monolayers was also investigated. RESULTS: The 18-kDa form of Fel d 1 caused
      degradation of denatured collagens (gelatin) and cleaved a 20-kDa fragment from
      the A chain of plasma fibronectin. Catalytic activity was not altered by
      inhibitors of cysteine peptidases, matrix metallopeptidases or by removal of
      divalent cations. In contrast, aprotinin and TLCK were inhibitors of Fel d 1. The
      absence of a serine peptidase catalytic triad in Fel d 1, together with the
      stoichiometry of the inhibition of TLCK and aprotinin, suggest that their
      inhibitory action may be due to noncatalytic site interactions. Alternatively,
      highly purified Fel d 1 may be associated with an active contaminant, although
      none were found. CONCLUSION: These results suggest that Fel d 1 is another
      example of a domestic allergen which is associated with enzyme activity. It
      remains to be established whether the activity resides in Fel d 1 itself or in an
      unresolved, and possibly related, protein.

PMID- 10931116
TI  - Association of beta2-adrenergic receptor polymorphisms with severe asthma.
AB  - BACKGROUND: There is considerable interest in the role of different candidate
      loci in the development of asthma. This study investigates the association
      between asthma severity and previously identified polymorphisms at two sites
      within the beta2-adrenergic receptor (beta2AR) gene: the Arg16-->Gly16 and Gln27-
      >Glu27 alleles. METHODS: Restriction enzyme analysis of amplified beta2AR gene
      products (PCR-RFLP) was used to analyse the frequency of the Arg16-->Gly16 and
      Gln27-->Glu27 polymorphisms within the beta2AR gene in 95 severe asthmatic
      patients (with a markedly increased risk of death from asthma), 59 mild asthmatic
      patients, and a control group of 92 nonasthmatic subjects. RESULTS: The Gly16
      polymorphism was significantly associated with asthma severity with odds ratios
      (95% CI) for the Gly16 allele being 1.56 (1.02-2.40, P = 0.04) and 0. 98 (0.61
      1.57, P = 0.92) for the severe and mild asthma groups, respectively. The
      corresponding odds ratios (95% CI) for Gly16 homozygotes were 1.91 (0.82-4.41, P
      = 0.13) and 0.82 (0.35-1.92, P = 0.65) for the severe and mild asthma groups,
      respectively. There was no significant association between either polymorphism at
      amino acid 27 and asthma or asthma severity. CONCLUSIONS: We conclude that the
      polymorphisms of amino acids 16 and 27 of the beta2AR gene are not associated
      with the development of asthma per se, but that the Gly16 polymorphism may play a
      role in the pathogenesis of asthma severity.

PMID- 10931118
TI  - Nerve growth factor prevents apoptosis of cord blood-derived human cultured mast
      cells synergistically with stem cell factor.
AB  - BACKGROUND: Stem cell factor (SCF) has been identified as a critical survival
      factor of human mast cells. Other cytokines which possess survival promotion
      activity on human mast cells are less known. OBJECTIVE: We examined the survival
      promotion activity of nerve growth factor (NGF) on cord blood-derived human
      cultured mast cells. METHODS: Expression and function of NGF receptors on the
      mast cells were examined by RT PCR, flowcytometric analysis, immunoprecipitaion
      and western blotting. The survival promotion activity of NGF to the mast cells
      was examined. To evaluate the proliferating activity of NGF on the human cultured
      mast cells, flow cytometric analysis with propidium iodide staining was applied.
      To confirm whether the human mast cell growth activity of NGF was caused by a
      suppression of apoptosis, the proportion of the cells containing in situ DNA
      fragmentation was counted. RESULTS: The human cultured mast cells expressed the
      high affinity receptor p140trk but not the low affinity receptor p75LNGFR. NGF
      induced the phosphorylation of p140trk. NGF alone could not support the survival
      of the mast cells, however, the addition of NGF to the culture medium containing
      recombinant SCF led to a significant increase of the number of survival mast
      cells. No significant changes of the cell cycle from G0/G1 phase to the S/G2 + M
      phases were observed by NGF. In contrast, the addition of NGF to the medium with
      SCF showed a significant inhibitory effect on the apoptosis of the mast cells.
      CONCLUSION: NGF may act as a key factor to promote the survival of human mast
      cells synergistically with SCF through the prevention of apoptosis.

PMID- 10931117
TI  - Lung epithelial H292 cells induce differentiation of immature human HMC-1 mast
      cells by interleukin-6 and stem cell factor.
AB  - BACKGROUND: Immature mast cells migrate into tissues where they differentiate
      into mature mast cells under the influence of local factors. In the airways of
      asthmatics increased numbers of chronically activated mast cells are located
      nearby the airway epithelium. OBJECTIVE: The aim of this study was to evaluate
      whether and, if so, which products released by epithelial cells may affect mast
      cell proliferation and differentiation. METHODS: We performed in vitro studies
      using the human lung mucoepidermoid carcinoma-derived H292 cell line and the
      immature human mast cell line, HMC-1. Proliferation was assessed by 3H-thymidine
      incorporation. Differentiation of HMC-1 cells was inferred from tryptase
      production. RESULTS: Exposure of HMC-1 cells to medium conditioned for 48 h by
      H292 cells resulted in a reduction of proliferation with 65 +/- 4.9% (mean +/-
      SEM, n = 9) at day 5. Culturing HMC-1 cells for 8 days in the presence of H292
      conditioned medium resulted in morphological changes indicative of
      differentiation, and in a 3.0 +/- 0.4-fold increase of tryptase production (P =
      0.0039, n = 9). Conditioned medium from H292 cells that were stimulated by LPS
      also inhibited HMC-1 proliferation. Inhibitory antibodies against two mediators
      from H292 cells, interleukin-6 (IL-6) and stem cell factor (SCF), abolished the
      increase in HMC-1 tryptase production induced by H292-conditioned medium.
      Recombinant human (rh) IL-6, but not rhSCF, reduced HMC-1 proliferation with 44%
      and 13% at day 3 and 5, respectively. Surprisingly, rhIL-6 did not increase HMC-1
      tryptase production significantly whereas incubation with rhSCF did (1.5 +/- 0.1
      fold, P = 0.002, n = 10) although the increase was less than observed for
      conditioned medium. CONCLUSION: Epithelial-derived IL-6 and SCF are implicated in
      differentiation of HMC-1 cells but additional factors are not excluded. As
      activated primary bronchial epithelial cells also express IL-6 and SCF, it should
      be considered that these cells are involved in mast cell differentiation within
      the airways, particularly in diseases where epithelial cells are activated, such
      as asthma.

PMID- 10931119
TI  - Late onset reactions to oral food challenge are linked to low serum interleukin
      10 concentrations in patients with atopic dermatitis and food allergy.
AB  - BACKGROUND: Aberrant cytokine production in vitro has been associated with atopic
      disease. No study has as yet been made of the circulating cytokine profiles in
      atopic patients with food allergy in response to oral allergen challenge.
      OBJECTIVE: To assess the effect of oral allergen challenge on the serum cytokine
      concentrations in patients with atopic dermatitis and food allergy. METHODS:
      Serum concentrations of interleukin (IL)-10, transforming growth factor beta 1,
      IL-1ra, IL-6, IL-5, IL-4 and interferon (IFN)-gamma were measured before and
      after double-blind, placebo-controlled food challenges (DBPCFC) (n = 73). Before
      DBPCFC, combined skin prick and patch testing was performed for cow milk, egg,
      soybean and cereals, and production of IFNgamma, IL-4, IL-10 and tumour necrosis
      factor alpha (TNFalpha) was determined in supernatants of cultures of peripheral
      blood mononuclear cells (PBMCs) stimulated by cow milk. RESULTS: The oral food
      challenge triggered immediate onset exanthematous reactions in 22 cases and late
      onset eczematous reactions in 29. The late-reacting cases had more positive skin
      patch test and negative skin prick test reactivities with allergenic food, and
      they had lower serum IL10 concentrations than immediate-reacting cases. In
      challenge-positive cases, IL-10 concentrations increased from 2.9 (0.1-5.04)
      pg/mL to 3. 9 (1.2-8.3) pg/mL in response to DBPCFC, P = 0.05, median
      (interquartile ranges), but not in those tolerant to cow milk. PBMCs of patients
      with cow milk allergy but not of those tolerant to cow milk generated TNFalpha in
      response to cow milk in vitro. CONCLUSION: These results indicate that oral
      allergen challenge in atopic patients with food allergy triggers systemic release
      of IL-10. Patients with late onset reactions were found to have lower serum IL-10
      concentrations than their immediate-reacting counterparts. Considering that IL-10
      is an inhibitory cytokine of delayed-type hypersensitivity, low IL-10 in late
      reacting patients may explain the high frequency of their positive skin patch
      tests combined with negative skin prick tests.

PMID- 10931120
TI  - Bronchial responsiveness to methacholine is increased in citrus red mite
      (Panonychus citri)-sensitive children without asthmatic symptoms.
AB  - BACKGROUND: A recent investigation has suggested that citrus red mite (Panonychus
      citri, CRM) is a common sensitizing allergen among children living around citrus
      farms. OBJECTIVE: A cross-sectional survey was performed to evaluate the
      bronchial responsiveness to methacholine in CRM-sensitive children without
      asthmatic symptoms. SUBJECTS AND METHODS: A total of 375 children living around
      citrus farms were enrolled in this study. There were 201 boys and 174 girls with
      a mean age of 12.5 (range 7-16) years. Each subject was evaluated by a
      questionnaire, a skin prick test with 13 common inhalant allergens including CRM,
      and a methacholine bronchial provocation test (MBPT). RESULTS: Positive rate of
      MBPT (PC20-methacholine < 25 mg/mL) was higher in atopic rhinitic and atopic
      control children than in nonatopic rhinitic and nonatopic control subjects (41.3%
      and 33.3% vs 17.2% and 15.4%, respectively, both P < 0.05). Slope of dose
      response curve (DRS, %/mg/mL) was higher in atopic rhinitic children than in
      nonatopic rhinitic, atopic control and nonatopic control subjects (14.3 +/- 0.87
      vs 9.4 +/- 0.72, 10.0 +/- 1.37 and 9.2 +/- 1.51, P < 0.05, respectively). Both
      the positive rate of MBPT and the DRS were increased in children with positive
      skin response to CRM than in those without sensitization (48.2% vs 22.9%, P =
      0.0001; 15.6 +/- 1.26 vs 10.2 +/- 0.65, P = 0.0001). CONCLUSION: Bronchial
      responsiveness is increased in citrus red mite-sensitive children even if they
      have no asthmatic symptoms.

PMID- 10931121
TI  - The psychological burden of peanut allergy as perceived by adults with peanut
      allergy and the parents of peanut-allergic children.
AB  - BACKGROUND: Peanut-allergic patients are affected by a condition which forces
      them and their families to exercise extreme dietary vigilance and experience
      constant uncertainty throughout their lives. OBJECTIVE: To compare the quality of
      life and family relations of children and adults with a peanut allergy to that of
      children and adults with a rheumatological disease. METHODS: Patients with a
      confirmed diagnosis of peanut allergy or a rheumatological disease completed (for
      children less than 18 years, by proxy) self-report questionnaires regarding the
      impact of their condition on their quality of life and family relations. A
      vertical visual analogue scale and the Impact on Family Questionnaire (IFQ)
      served as outcome measures. RESULTS: One hundred and fifty-three peanut-allergic
      children were compared with 69 children with a rheumatological disease while 37
      peanut-allergic adults were compared with 42 adults with a rheumatological
      disease. The parents of peanut-allergic children, compared to the parents of
      children with a rheumatological disease, reported that their children had
      significantly more disruption in their daily activities. Furthermore, the parents
      of peanut-allergic children reported more impairment in the familial-social
      dimension of the IFQ. Conversely, adults with a chronic rheumatological disease
      reported more disruption in their family relations than peanut-allergic adults.
      CONCLUSION: Given the considerable disruption in daily activities and family
      relations reported by the parents of peanut-allergic children, accurate diagnosis
      of peanut allergy is essential. Our work should make health care professionals
      dealing with children with confirmed peanut allergy more aware of the support
      that these families may require. Furthermore, we hope to motivate food industries
      to offer more 'peanut free' products to decrease the dietary restrictions of
      these patients while minimizing their potential for accidental ingestion.

PMID- 10931122
TI  - Lessons for management of anaphylaxis from a study of fatal reactions.
AB  - BACKGROUND: The unpredictability of anaphylactic reactions and the need for
      immediate, often improvised treatment will make controlled trials impracticable;
      other means must therefore be used to determine optimal management. OBJECTIVES:
      This study aimed to investigate the circumstances leading to fatal anaphylaxis.
      METHODS: A register was established including all fatal anaphylactic reactions in
      the UK since 1992 that could be traced from the certified cause of death. Data
      obtained from other sources suggested that deaths certified as due to anaphylaxis
      underestimate the true incidence. Details of the previous medical history, the
      reaction and necropsy were sought for all cases. RESULTS: Approximately half the
      20 fatal reactions recorded each year in the UK were iatrogenic, and a quarter
      each due to food or insect venom. All fatal reactions thought to have been due to
      food caused difficulty breathing that in 86% led to respiratory arrest; shock was
      more common in iatrogenic and venom reactions. The median time to respiratory or
      cardiac arrest was 30 min for foods, 15 min for venom and 5 min for iatrogenic
      reactions. Twenty-eight per cent of fatal cases were resuscitated but died 3 h-30
      days later, mostly from hypoxic brain damage. Adrenaline (epinephrine) was used
      in treatment of 62% of fatal reactions but before arrest in only 14%.
      CONCLUSIONS: Immediate recognition of anaphylaxis, early use of adrenaline,
      inhaled beta agonists and other measures are crucial for successful treatment.
      Nevertheless, a few reactions will be fatal whatever treatment is given; optimal
      management of anaphylaxis is therefore avoidance of the cause whenever this is
      possible. Predictable cross-reactivity between the cause of the fatal reaction
      and that of previous reactions had been overlooked. Adrenaline overdose caused at
      least three deaths and must be avoided. Kit for self-treatment had proved
      unhelpful for a variety of reasons; its success depends on selection of
      appropriate medication, ease of use and good training.

PMID- 10931123
TI  - Effect of a 4-week treatment with theophylline on sputum eosinophilia and sputum
      eosinophil chemotactic activity in steroid-naive asthmatics.
AB  - BACKGROUND: The precise mechanism of action of theophylline in asthma is not
      fully understood but recent data have drawn attention to its potential anti
      inflammatory effect. OBJECTIVE: The purpose of this study was to assess the
      effect of theophylline on sputum eosinophilia and sputum eosinophil chemotactic
      activity in steroid-naive asthmatics. METHOD: We performed a 4-week randomized
      double-blind, placebo-controlled, parallel group study in 21 mild to moderate
      steroid-naive asthmatics whose sputum eosinophilia was found twice > 5% during
      the run in period. Eleven subjects received 600 mg/24 h theophylline for the
      first 2 weeks and 900 mg/24 h for the last 2 weeks while 10 subjects took a
      placebo for 4 weeks. Sputum was induced after 2 and 4 weeks of treatment and 1
      week after stopping the treatment. The sputum samples were compared for their
      cell counts, eosinophil cationic protein (ECP) levels and eosinophil chemotactic
      activity using micro-Boyden chambers. RESULTS: Serum theophylline concentrations
      reached 7 and 11 microg/mL at V3 and V4, respectively. Intragroup comparisons
      showed that theophylline, but not placebo, caused a significant reduction in
      sputum eosinophil counts at V3 (62 +/- 10% from baseline, P < 0.01) and a strong
      trend at V4 (67 +/- 16% from baseline, P = 0.07) when compared to baseline. The
      intergroup difference obtained after comparing the area under the curve over the
      4 week treatment period only approached the statistical significance (P = 0.08).
      At baseline the fluid phase of the sputum contained a significant eosinophil
      chemotactic activity which was inhibited after a 4-week treatment by theophylline
      (P < 0. 01) but not by placebo. The mean sputum theophylline levels after 4 weeks
      of treament (1.7 microg/mL) was lower than that required to cause significant
      inhibition of eosinophil chemotaxis in vitro. CONCLUSION: Theophylline decreases
      the natural sputum eosinophil chemotactic activity present in asthmatics.
      However, when using a small sample size, the 35% reduction in sputum eosinophilia
      achieved by theophylline failed to reach statistical significance when compared
      to that seen after placebo.

PMID- 10931124
TI  - Warfarin treatment of chronic idiopathic urticaria and angio-oedema.
AB  - BACKGROUND: Chronic idiopathic urticaria is a disabling condition that does not
      always respond to antihistamine drugs and other agents are sometimes needed to
      control disease activity. Warfarin has demonstrated efficacy in single unblinded
      case studies [1] but has been dismissed by others [2]. OBJECTIVE: We investigated
      the effect of warfarin treatment in eight patients with chronic idiopathic
      urticaria unresponsive to antihistamines in an open study. Six of the eight
      patients responded to treatment and three had a dramatic response. These three
      were included in a double-blind placebo-controlled trial of warfarin therapy to
      confirm significant benefit from treatment. METHODS: The three warfarin
      responders had their stable warfarin dose encapsulated and placebo capsules were
      provided. A double-blind placebo-controlled crossover trial was performed on each
      patient. Visual analogue scores recorded disease activity. RESULTS: Comparison of
      visual analogue scores showed a significant benefit while on warfarin with a
      reduction in pruritus and angio-oedema. CONCLUSION: This is the first double
      blind placebo-controlled study to show a response of chronic idiopathic urticaria
      to warfarin. The mechanisms of action are unclear and require further study.

PMID- 10931125
TI  - Diagnosis of venom allergy by flow cytometry. Correlation with clinical history,
      skin tests, specific IgE, histamine and leukotriene C4 release.
AB  - BACKGROUND: Potent allergens such as hymenoptera venoms are capable of inducing
      severe and life threatening clinical reactions. Percentage of false negative
      results obtained by the usual diagnostical methods is comprised between 10 and
      25%. OBJECTIVE: Evaluation of the sensitivity and the specificity of cellular
      tests and particularly evaluation of a new flow cytometric method. METHODS: Forty
      five allergic patients having experienced a local, a systemic reaction or an
      anaphylactic shock and 10 controls having undergone hymenoptera stings without
      clinical reactions were selected on the basis of the clinical history, skin tests
      and specific IgE. Three cellular tests were performed on the same cell
      suspensions and in the presence of 2 ng/mL of rIL3: histamine release (RIA),
      leukotriene C4 release (ELISA) and basophil activation test (flow cytometry after
      double anti-IgE FITC, anti-CD63 PE labelling). RESULTS: As compared to the
      clinical history, sensitivities of skin tests, specific IgE, flow cytometry,
      histamine release and leukotriene release were, respectively; 85%, 88%, 100%, 89%
      and 100%. Flow cytometric analysis of basophil activation showed a significant
      decrease of the mean fluorescence density and number of IgE positive cells and a
      significant increase of the number of CD63 positive cells. The 10 controls tested
      by flow cytometry were negative. CONCLUSION: As compared to the clinical history
      and to the other parameters tested here, flow cytometry showed a high sensitivity
      and a high specificity. The excellent correlation observed between this method
      and the other cellular tests such as histamine and leukotriene release are in
      favour of the specificity of flow cytomery and in favour of the use of this
      method for venom allergy diagnosis.

PMID- 10931126
TI  - A randomized trial of dehumidification in the control of house dust mite.
AB  - BACKGROUND: House dust mites (HDM) are sensitive to humidity. Few studies have
      adequately examined the potential of dehumidification in reducing HDM numbers.
      OBJECTIVE: The study examined the effect of portable domestic dehumidifiers, and
      a behavioural programme to reduce humidity, on HDM counts and HDM allergen
      levels. METHODS: A randomized controlled trial was undertaken. A total of 76
      homes were allocated to three groups that received a portable domestic
      dehumidifier, a behavioural programme, or no intervention. Humidity, temperature,
      HDM counts (trap and vacuum samples), HDM allergen, and other details of the home
      environment were measured on four occasions over a period of 1 year.
      Interventions and measurements were concerned predominantly with one bedroom.
      RESULTS: There was a reduction in relative humidity in the dehumidifier group,
      but not the behavioural group. A decline in HDM trap counts was observed for all
      three groups. Change scores did not indicate that the dehumidifier group had a
      greater decline than the other groups. A secondary analysis examining presence or
      absence of HDM showed a shift from households having HDM at baseline to
      households not having HDM in the final round for some trap measures. Change score
      analysis indicated that this shift was greater in the dehumidifier group compared
      with other groups. The dehumidifier group did not show a greater decline in HDM
      allergen than that seen in the other two groups. CONCLUSION: Neither the
      dehumidifier nor the behavioural intervention had a major effect on HDM counts or
      allergen levels. However, the study did have a number of limitations relating to
      size, timing of intervention, and running of the dehumidifiers. The secondary
      data analysis may indicate some effect of dehumidification, but clearly this
      effect was small. There is a need for more information on the effects of reducing
      ambient humidity on the distribution of HDM within their habitats.

PMID- 10931127
TI  - Validation of the ISAAC video questionnaire (AVQ3.0) in adolescents from a mixed
      ethnic background.
AB  - BACKGROUND: The International Study of Asthma and Allergies in Childhood (ISAAC)
      has developed an international version of the asthma video questionnaire (AVQ3.0)
      to measure asthma prevalence. This questionnaire has not been validated in
      adolescents from a mixed ethnic background. OBJECTIVE: The aims of this study
      were to compare the video questionnaire with a written questionnaire in the
      detection of airway hyperresponsiveness to hypertonic saline in a population of
      adolescents from a mixed ethnic background, and to establish the repeatability
      and psychometric properties of the asthma video questionnaire. METHODS: The study
      was conducted in four secondary schools in Sydney, an area with a high proportion
      of people from a non-English speaking background. Four hundred and seventy-five
      students from schools 1 and 2 completed the video questionnaire and a subgroup of
      these students (n = 170) completed the written questionnaire and a hypertonic
      saline inhalation challenge. Reproducibility of the questionnaire was evaluated
      by administering the questionnaire to a subsample of students 2 weeks later. The
      psychometric properties of the video questionnaire were examined in 852 students
      at two other schools (schools 3 and 4). RESULTS: One hundred and sixty-nine
      students aged 13.5 (sd 1.3) years completed both written and video
      questionnaires, and the hypertonic saline challenge. The students had widely
      different cultural backgrounds including Asian, South Pacific, Middle Eastern,
      European and African countries. There was good agreement between the
      questionnaires for wheeze (kappa 0.42). Questions on the video questionnaire
      concerning wheezing had good sensitivity (90%) and specificity (68%) for airway
      hyperresponsiveness to hypertonic saline. The video questionnaire was
      reproducible (kappa 0.82), had good internal consistency (Cronbach's alpha 0.81)
      and each question pertained to a single construct explaining 58% of the variance
      in total score. CONCLUSION: This study has validated the international version of
      the ISAAC video questionnaire against airway hyperresponsiveness to hypertonic
      saline in adolescents from a mixed ethnic background, and identified that the
      questionnaire has good psychometric properties. The ISAAC video has proved to be
      a valuable tool for the assessment of asthma prevalence in populations of ethnic
      diversity.

PMID- 10931128
TI  - TAP deficiency syndrome.

PMID- 10931129
TI  - Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates
      with increased use of superantigen-reactive Vbeta-chains in cutaneous lymphocyte
      associated antigen (CLA)-positive lymphocytes.
AB  - Staphylococcal superantigens have been implicated in the pathogenesis of atopic
      dermatitis (AD). This may occur through superantigenic activation of T
      lymphocytes and their subsequent induction of the skin homing receptor CLA on
      activated cells. We investigated the proliferative responses of peripheral blood
      mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD
      and six normal controls to the staphylococcal superantigens, staphylococcal
      enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the
      mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed
      CLA and T cell receptor (TCR) Vbeta-chain expression by immunofluorescence and
      flow cytometry before and after stimulation. PBMC from AD patients showed two
      fold increased proliferation to SEA and SEB (P < 0.01) compared with normals,
      whereas the response to mitogenic stimulation was identical. Analysis of (TCR)
      Vbeta-chain expression demonstrated increased use of superantigen-reactive Vbeta
      families in freshly isolated PBMC in AD patients compared with controls. This
      pattern of Vbeta-chain expression was only observed in the CLA+ but not the total
      population of T cells. Furthermore, there was a positive correlation between the
      enhanced PBMC proliferative response and increased expression of superantigen
      reactive Vbeta families in atopic patients. These data support the concept that
      superantigens are important in the pathogenesis of this common condition, and
      also provide evidence that the increased use of certain Vbeta families in
      circulating, CLA+, skin homing lymphocytes is of functional significance.

PMID- 10931130
TI  - Soluble CD30 is more relevant to disease activity of atopic dermatitis than
      soluble CD26.
AB  - It is suggested that CD30 and CD26 are surface molecules expressed on activated
      Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26
      (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions
      were aggravated and in non-atopic healthy controls, and then analysed the
      possible correlation between these values and the levels of several clinical
      markers. The plasma levels of both sCD30 and sCD26 were significantly higher in
      AD patients than in controls, both in exacerbation status and after conventional
      treatment. Multiple regression analyses showed that plasma sCD30 was a much
      better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the
      area and the score of AD eruption than sCD26, although elevated levels of both
      sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly,
      sCD30 plasma levels decreased significantly in AD patients after conventional
      treatment, while no significant transition was noted in the concentration of
      sCD26. Moreover, a significant reduction of sCD30 levels was observed in the
      group of patients whose eruption score was reduced > 50%, whereas it was not in
      those < 50%. These findings provide evidence that the successful treatment of AD
      is associated with down-activation of Th2.

PMID- 10931131
TI  - Booster immunization of children with an acellular pertussis vaccine enhances Th2
      cytokine production and serum IgE responses against pertussis toxin but not
      against common allergens.
AB  - Acellular pertussis vaccines (Pa) protect against severe pertussis in children.
      However, serum antibody responses decline quickly after immunization. Studies in
      animal models suggest that cell-mediated immunity also contributes to protection
      against Bordetella pertussis, and it has already been demonstrated that Pa induce
      T cells that secrete type-1 and type-2 cytokines in children. In this study we
      examined the persistence of the T cell response and the effect of booster
      immunization in 4-6-year-old children. Cell-mediated immunity to B. pertussis
      antigens was detected in a high proportion of children more than 42 months after
      their last immunization. Peripheral blood mononuclear cells (PBMC) from the
      majority of children secreted interferon-gamma (IFN-gamma) and a smaller
      proportion IL-5, in response to specific antigen stimulation in vitro. However,
      following booster immunization, significantly higher concentrations of IL-5, but
      not IFN-gamma, were produced by PBMC in response to B. pertussis antigens.
      Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN
      gamma concentrations were reduced following booster immunization. It has been
      suggested that childhood immunization with Th2-inducing vaccines may predispose
      some children to atopic disease. Although we found that pertussis toxin (PT)
      specific IgE was significantly increased after booster immunization in both
      atopic and non-atopic children, the levels of IgE to common allergens and the
      prevalence of positive skin prick test were unaffected by the booster
      vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis
      antigens, booster vaccination with Pa does not appear to be a risk factor for
      allergy.

PMID- 10931132
TI  - Analysis of the autoimmune epitopes on human testicular NASP using recombinant
      and synthetic peptides.
AB  - The human nuclear autoantigenic sperm protein, NASP, is a testicular histone
      binding protein of 787 amino acids to which most vasectomized men develop
      autoantibodies. In this study to define the boundaries of antigenic regions and
      epitope recognition pattern, recombinant deletion mutants spanning the entire
      protein coding sequence and a human NASP cDNA sublibrary were screened with
      vasectomy patients' sera. Employing panel sera from 21 vasectomy patients with
      anti-sperm antibodies, a heterogeneous pattern of autoantibody binding to the
      recombinant polypeptides was detected in ELISA and immunoblotting. The majority
      of sera (20/21) had antibodies to one or more of the NASP fusion proteins.
      Antigenic sites preferentially recognized by the individual patients' sera were
      located within aa 32-352 and aa 572-787. Using a patient's serum selected for its
      reactivity to the whole recombinant protein in Western blots, cDNA clones
      positive for the C-terminal domain of the molecule were identified. The number
      and location of linear epitopes in this region were determined by synthetic
      peptide mapping and inhibition studies. The epitope-containing segment was
      delimited to the sequence aa 619-692 and analysis of a series of 74 concurrent
      overlapping 9mer synthetic peptides encompassing this region revealed four linear
      epitopes: amino acid residues IREKIEDAK (aa 648-656), KESQRSGNV (aa 656-664),
      AELALKATL (aa 665-673) and GFTPGGGGS (aa 680-688). All individual patients' sera
      reacted with epitopes within the sequence IREellipsis.GGS (aa 648-688). The
      strongest reactivity was displayed by peptides corresponding to the sequence
      AELALKATL (aa 665-673). Thus, multiple continuous autoimmune epitopes in NASP
      involving sequences in the conserved C-terminal domain as well as in the less
      conserved testis-specific N-terminal region comprising the histone-binding sites,
      as predicted for an antigen-driven immune response, may be a target of
      autoantibodies in vasectomized men and may provide a relevant laboratory variable
      to describe more accurately the spectrum of autoantibody specificities associated
      with the clinical manifestation of vasectomy.

PMID- 10931133
TI  - CD8+ T cells are crucial for the ability of congenic normal mice to reject highly
      immunogenic sarcomas induced in nude mice with 3-methylcholanthrene.
AB  - An attempt was made to identify the selection pressures put upon a growing tumour
      by CD8+ T cells. To this end tumours induced with 3-methylcholanthrene in T cell
      deficient nude mice and in congenic T cell-competent nu/+ mice were transplanted
      to nu/+ recipients. The rejection rate of the sarcomas from nude mice was almost
      twice that of the sarcomas from nu/+ mice. Depletion of CD8+ T cells from nu/+
      recipients prior to transplantation made them accept nude tumours that were
      consistently rejected by untreated nu/+ recipients. These findings suggest that a
      methylcholanthrene sarcoma during its growth in a T cell-competent host adapts to
      the T cell system through a selective elimination of highly immunogenic tumour
      cells that are susceptible to CD8+ T cell-mediated lysis.

PMID- 10931134
TI  - Immunotherapy of a human papillomavirus (HPV) type 16 E7-expressing tumour by
      administration of fusion protein comprising Mycobacterium bovis bacille Calmette
      Guerin (BCG) hsp65 and HPV16 E7.
AB  - Human papillomavirus type 16 (HPV16) infection has been linked to the development
      of cervical and anal dysplasia and cancer. One hallmark of persistent infection
      is the synthesis of the viral E7 protein in cervical epithelial cells. The
      expression of E7 in dysplastic and transformed cells and its recognition by the
      immune system as a foreign antigen make it an ideal target for immunotherapy.
      Utilizing the E7-expressing murine tumour cell line, TC-1, as a model of cervical
      carcinoma, an immunotherapy based on the administration of an adjuvant-free
      fusion protein comprising Mycobacterium bovis BCG heat shock protein (hsp)65
      linked to HPV16 E7 (hspE7) has been developed. The data show that prophylactic
      immunization with hspE7 protects mice against challenge with TC-1 cells and that
      these tumour-free animals are also protected against re-challenge with TC-1
      cells. In addition, therapeutic immunization with hspE7 induces regression of
      palpable tumours, confers protection against tumour re-challenge and is
      associated with long-term survival (> 253 days). In vitro analyses indicated that
      immunization with hspE7 leads to the induction of a Th1-like cell-mediated immune
      response based on the pattern of secreted cytokines and the presence of cytolytic
      activity following antigenic recall. In vivo studies using mice with targeted
      mutations in CD8 or MHC class II or depleted of CD8 or CD4 lymphocyte subsets
      demonstrate that tumour regression following therapeutic hspE7 immunization is
      CD8-dependent and CD4-independent. These studies extend previous observations on
      the induction of cytotoxic T lymphocytes by hsp fusion proteins and are
      consistent with the clinical application of hspE7 as an immunotherapy for human
      cervical and anal dysplasia and cancer.

PMID- 10931135
TI  - The C5a receptor is expressed by human renal proximal tubular epithelial cells.
AB  - The C5a receptor is expressed by a variety of cell types. These studies
      demonstrate by immunohistochemistry that the receptor is present on the surface
      of proximal and distal tubular epithelial cells from normal kidney. In addition,
      the receptor was detected on transitional epithelial cells of the ureter and
      bladder. Primary proximal tubular cultures and a proximal tubular cell line both
      also expressed the C5a receptor, as demonstrated by immunofluorescence and by
      FACS analysis. The presence of mRNA encoding the receptor was confirmed by
      reverse transcriptase-polymerase chain reaction analysis. As opposed to its
      effect on glomerular mesangial cells, the receptor did not mediate a
      proliferative response by the proximal tubular cells. C5a also did not enhance
      the synthesis/secretion of transforming growth factor-beta 1, monocyte
      chemoattractant protein-1, platelet-derived growth factor-AB or tumour necrosis
      factor-alpha by cultured proximal tubular cells. Therefore, although the C5a
      receptor clearly is expressed by proximal tubular cells, clarification of its
      functional relevance on this cell type awaits further studies.

PMID- 10931136
TI  - Cytokine-mediated up-regulation of CD55 and CD59 protects human hepatoma cells
      from complement attack.
AB  - Hepatic parenchymal cells respond in many different ways to acute-phase
      cytokines. Some responses may protect against damage by liver-derived
      inflammatory mediators. Previous investigations have shown that cytokines cause
      increased secretion by hepatoma cells of soluble complement regulatory proteins,
      perhaps providing protection from complement attack. More important to cell
      protection are the membrane complement regulators. Here we examine, using flow
      cytometry and Northern blotting, the effects of different cytokines, singly or in
      combination, on expression of membrane-bound complement regulators by a hepatoma
      cell line. The combination of tumour necrosis factor-alpha, IL-1beta, and IL-6
      caused increased expression of CD55 (three-fold) and CD59 (two-fold) and
      decreased expression of CD46 at day 3 post-exposure. Interferon-gamma reduced
      expression of CD59 and strongly antagonized the up-regulatory effects on CD59
      mediated by the other cytokines. Complement attack on antibody-sensitized
      hepatoma cells following a 3-day incubation with the optimum combination of acute
      phase cytokines revealed increased resistance to complement-mediated lysis and
      decreased C3b deposition. During the acute-phase response there is an increased
      hepatic synthesis of the majority of complement effector proteins. Simultaneous
      up-regulation of expression of CD55 and CD59 may serve to protect hepatocytes
      from high local concentrations of complement generated during the acute-phase
      response.

PMID- 10931137
TI  - Changed colonic profile of P-selectin, platelet-endothelial cell adhesion
      molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and
      ICAM-3 in inflammatory bowel disease.
AB  - Cell adhesion molecules (CAM) are essential for the capture and migration of
      leucocytes. Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by
      a continuous infiltration of leucocytes into intestinal tissue, and the colonic
      contents of P-selectin, PECAM-1, ICAM-1, ICAM-2, and ICAM-3 were therefore
      studied. Concentrations of these cell adhesion molecules were measured by an
      ELISA technique in sonicated colonic tissue from patients with UC and CD and
      controls with non-inflammatory disease and compared with the diagnosis and
      disease activity. P-selectin, PECAM-1, and ICAM-1 concentrations were elevated in
      UC patients compared with controls (P = 0.034, P = 0.014, P = 0.017,
      respectively), whereas that of ICAM-2 was not. The concentrations of these CAM
      did not differ in CD. In contrast, higher concentrations of ICAM-3 were found in
      the CD patients than in either UC (P = 0.001) or controls (P = 0.004). The CAM
      concentrations increased with disease activity, although only ICAM-1 was
      significantly elevated (P = 0.017). As considerable differences were found
      between UC and CD with comparable stages of inflammation, the mere presence of
      inflammation cannot solely explain the results. The observed differences in the
      CAM concentrations in UC and CD support the hypothesis that UC and CD are two
      distinct disease entities with separate pathogenic mechanisms.

PMID- 10931138
TI  - B cell epitopes of gliadin.
AB  - A phage displayed dodecapeptide library and synthetic octapeptides spanning the
      complete sequence of alpha- and gamma-type gliadin and overlapping in six amino
      acids (pepscan) were screened for binding to human gliadin antibodies (AGA).
      Phage display experiments led to four sequences recognized with significantly
      higher frequency by sera with raised IgA-AGA titres than by control sera. All
      these peptides contained the core sequence PEQ. Pepscan experiments revealed
      binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X
      representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and
      QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in alpha
      type gliadin; and (v) QPQQPF (IgG and IgA) in gamma-type gliadin. In two of the
      sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and
      QEQPFP, respectively, increased significantly binding of AGA from sera of
      patients with biopsy-proven or suspected coeliac disease (CoD), all positive for
      endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre
      from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not
      enhanced by this substitution. Thus, AGA directed against these modified epitopes
      can be regarded as specific for CoD. This is the first study demonstrating that
      deamidation of gliadin improves reactivity of AGA of CoD patients.

PMID- 10931139
TI  - Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis.
AB  - Ageing is associated with increased inflammatory activity in the blood. The
      purpose of this study was to investigate if age-related increased plasma levels
      of TNF-alpha were associated with atherosclerosis in a cohort of 130 humans aged
      81 years. The elderly cohort had increased circulating levels of TNF-alpha, C
      reactive protein (CRP), total cholesterol (TC), low-density lipoproteins (LDL)
      and a low high-density lipoprotein (HDL)/TC ratio compared with a young control
      group (n = 44). The elderly cohort was divided by tertiles into three subgroups
      with low, intermediate, and high levels of TNF-alpha, respectively. In the group
      with high TNF-alpha concentrations a significantly larger proportion had clinical
      diagnoses of atherosclerosis. Furthermore, weak correlations were found between
      TNF-alpha on one hand and blood concentrations of triglycerides, leucocytes, CRP
      and a low HDL/TC ratio on the other which are known as risk factors of
      atherogenesis and thromboembolic complications. No correlations were found
      between TNF-alpha, TC, LDL, or the body mass index. In conclusion, the present
      study shows that in a cohort of 81-year-old humans, high levels of TNF-alpha in
      the blood were associated with a high prevalence of atherosclerosis.

PMID- 10931140
TI  - T lymphocyte lines isolated from atheromatous plaque contain cells capable of
      responding to Chlamydia antigens.
AB  - Chlamydia pneumoniae infection is associated with atherosclerosis and the
      organism has been identified in arterial lesions. To determine whether T
      lymphocyte-mediated immune responses to Chlamydia antigens within plaque could
      contribute to pathogenesis, we have derived T cell lines from atherosclerotic
      plaques of 32 patients. Culture with IL-2 alone proved insufficient for cellular
      activation and expansion, but additional stimulation with phytohaemagglutinin
      (PHA) or recall antigens allowed consistent establishment of T cell lines.
      Furthermore, in cultures of approx. 500 tissue fragments, Chlamydia organisms
      proved as effective as other recall antigens in producing outgrowth of arterial T
      cells (20-25% wells produced T cell lines). Testing the antigen responsiveness of
      T cell lines showed that those derived using Chlamydia organisms were more likely
      to respond to Chlamydia (5/29+) than those isolated using other stimuli (6/69+
      for PHA; 5/57+ for PPD and tetanus toxoid (TT)). However, lines responsive to
      each of the recall antigens were observed. Using recombinant Chlamydia antigens,
      some Chlamydia-specific T cell lines were shown to respond to OMP2 and/or hsp60.
      Those recognizing Chlamydia hsp60 did not cross-react with human hsp60, but human
      hsp60-responsive lines were also observed. Thus, atherosclerotic plaque tissue
      contains a variety of memory T lymphocytes, and amongst these are cells capable
      of recognizing Chlamydia antigens. In a C. pneumoniae-infected plaque, such T
      cells may be activated by local antigen and could contribute to the inflammatory
      process in the arterial wall through CD40 ligand expression and cytokine
      secretion.

PMID- 10931141
TI  - Autoantibodies in the sera of patients with rheumatic heart disease:
      characterization of myocardial antigens by two-dimensional immunoblotting and N
      terminal sequence analysis.
AB  - The concept of antigenic mimicry in autoimmune diseases such as rheumatic fever
      has been under investigation for decades and the range of cross-reactive tissue
      antigens for streptococcal-induced antibodies identified in rheumatic heart
      disease is still expanding. To identify heart tissue-reactive antigens which may
      be implicated in the secondary immunopathogenesis of rheumatic fever, sera from
      56 patients with acute rheumatic heart disease were probed in two-dimensional
      Western blots for reactivity against heart tissue antigens. After two-dimensional
      immunoblot analysis, proteins were submitted to N-terminal amino acid sequence
      analysis. This analysis identified creatine kinase, two mitochondrial proteins
      and, at a low level, various stress proteins as cross-reactive myocardial
      antigens. Therefore, in addition to myosin, creatine kinase may represent another
      major antigen for autoreactive antibodies in rheumatic heart disease.
      Mitochondrial proteins have been implicated in the pathogenesis of inflammatory
      heart disease for some years, and in this study we have identified two
      mitochondrial proteins as relevant antigens in rheumatic heart disease.

PMID- 10931142
TI  - Characterization of T cell clones derived from lymph nodes and lungs of
      Pseudomonas aeruginosa-susceptible and resistant mice following immunization with
      heat-killed bacteria.
AB  - Pseudomonas aeruginosa-resistant BALB/c and susceptible C57Bl/6 (B6) mice were
      immunized with heat-killed Pseudomonas either in the foot pad or via the trachea,
      and panels of Pseudomonas-specific T cell clones were developed from lymph nodes
      and lungs. All clones from either strain, whether of lymph node or lung origin,
      were CD3+CD4+CD8-TCRalphabeta+. The efficacy of cloning from lymph node cells was
      comparable between BALB/c and B6 mice. All lymph node BALB/c clones proliferated
      in response to Pseudomonas antigen in a dose-dependent manner, and this response
      was MHC class II-restricted. Vigorous proliferation by a considerable proportion
      of B6 T cell clones occurred in the absence of specific antigen. Lymph node
      clones from either strain could be categorized as either Th1 or Th0 on the basis
      of interferon-gamma (IFN-gamma)/IL-4 production. In either mouse strain the
      efficacy of cloning from lung tissue was substantially lower than from lymph
      nodes, but the efficacy of cloning from BALB/c compared with B6 lungs was higher.
      Four lung T cell clones from BALB/c and two from B6 mice were expanded for
      further analyses, and an interstrain difference was observed in cytokine
      production. Both B6 lung T cell clones were Th1-like and produced IFN-gamma but
      not IL-4 and IL-10, whereas four BALB/c lung T cell clones were Th2-like and
      produced IL-4 and IL-10 but not IFN-gamma. These observations suggest that
      differences in the CD4+ Th response in the lung may contribute to differences
      among inbred mouse strains in the level of resistance to bronchopulmonary
      Pseudomonas infection.

PMID- 10931143
TI  - Differential effect of cholera toxin on CD45RA+ and CD45RO+ T cells: specific
      inhibition of cytokine production but not proliferation of human naive T cells.
AB  - We have studied how cholera toxin (CT) and its non-toxic cell-binding B-subunit
      (CTB) affect the activation of pure human T cells in an anti-CD3-driven system.
      CT, as opposed to CTB, strongly suppressed the proliferative responses as well as
      cytokine production in CD4+ and CD8+ T cells. CT however, had a differential
      effect on naive and activated/memory T cell subsets. Costimulation through
      exogenous IL-2 or through CD28 cross-linking rescued the proliferation of CT
      treated naive CD45RA+ T cells, but not of activated/memory CD45RO+ cells. IL-2
      production and IL-2 receptor expression were markedly reduced by CT in all T cell
      fractions, i.e. also in CD45RA+ cells which had maintained proliferative
      responses. However, the proliferative responses of CT-treated CD45RA+ T cells
      were IL-2-dependent, as shown by blocking experiments using anti-IL-2 antibodies.
      These results indicate (i) that CTB has no cytostatic effect on human T cells,
      (ii) that CT affects proliferation and cytokine production by two different
      signal pathways, and (iii) that CT might interact with a signal pathway generated
      through or influenced by CD45.

PMID- 10931144
TI  - Growth of Brucella abortus in macrophages from resistant and susceptible mouse
      strains.
AB  - C57Bl/10 mice have a superior ability to control chronic infections with virulent
      strains of the intracellular bacteria Brucella abortus compared with BALB/c mice.
      While a number of differences in the cytokines produced by lymphocytes following
      infection of these two strains of mice have been shown, macrophages have not been
      evaluated for their role in conveying relative resistance. The importance of
      macrophages in control of brucella infections is demonstrated by the observations
      that intracellular survival of various strains of B. abortus directly correlates
      with their virulence in vivo, and the ability of macrophages to control brucellae
      in vitro has been shown to correlate with a brucella-resistant phenotype in
      ruminants. While both BALB/c and C57Bl are Nramp-susceptible mouse strains,
      additional differences in macrophage function outside of the Nramp1 gene effects
      could influence susceptibility to brucellosis. The studies conducted here
      comparing the ability of macrophages from C57Bl/10 and BALB/c mice indicate that
      the macrophages from resistant mice did not control intracellular growth of B.
      abortus strain 2308 more efficiently than those from the susceptible mice, either
      in the absence of, or following, interferon-gamma activation or iron
      supplementation. A number of different conditions for culturing macrophages were
      evaluated to rule out the influence of antibiotics on the conclusions drawn from
      the results.

PMID- 10931145
TI  - The 75-kD tumour necrosis factor (TNF) receptor is specifically up-regulated in
      monocytes during Q fever endocarditis.
AB  - Q fever is an infectious disease caused by Coxiella burnetii, an obligate
      intracellular microorganism that inhabits monocytes/macrophages. The dysregulated
      production of TNF-alpha in Q fever endocarditis has been associated with
      defective killing of C. burnetii by patient monocytes. As soluble receptors for
      TNF-alpha (TNF-R55 and TNF-R75) regulate TNF-alpha activity, we investigated
      their release by monocytes in Q fever. Spontaneous and C. burnetii-stimulated
      release of TNF-R75, but not of TNF-R55, was up-regulated in patients with ongoing
      endocarditis compared with controls. The increase in TNF-R75 release was related
      to the activity of Q fever endocarditis, since TNF-R75 release was similar in
      patients with cured endocarditis and controls. While spontaneous release of TNF
      R75 by monocytes from patients with ongoing Q fever endocarditis occurred without
      changes in its membrane expression, C. burnetii increased the surface expression
      of TNF-R75. In addition, TNF-R75 transcripts were increased in resting and C.
      burnetii-stimulated monocytes from patients with ongoing endocarditis. On the
      other hand, TNF-R75 release was not related to TNF-alpha secretion. These results
      indicate that the modulation of TNF-R75 is a critical feature of the
      pathophysiology of Q fever endocarditis.

PMID- 10931146
TI  - Comparative roles of free fatty acids with reactive nitrogen intermediates and
      reactive oxygen intermediates in expression of the anti-microbial activity of
      macrophages against Mycobacterium tuberculosis.
AB  - We assessed the role of free fatty acids (FFA) in the expression of the activity
      of macrophages against Mycobacterium tuberculosis in relation to the roles of two
      major anti-microbial effectors, reactive nitrogen intermediates (RNI) and
      reactive oxygen intermediates (ROI). Intracellular growth of M. tuberculosis
      residing inside macrophages was accelerated by treatments of macrophages with
      either quinacrine (phospholipase A2 (PLA2) inhibitor), arachidonyl
      trifuloromethylketone (type IV cytosolic PLA2 inhibitor), NG-monomethyl-L
      arginine (nitric oxide synthase inhibitor), and superoxide dismutase plus
      catalase (ROI scavengers). In addition, M. tuberculosis-infected macrophages
      produced and/or secreted these effectors sequentially in the order ROI (0-3 h),
      FFA (0-48 h), and RNI (3 to at least 72 h). Notably, membranous FFA (arachidonic
      acid) of macrophages translocated to M. tuberculosis residing in the phagosomes
      of macrophages in phagocytic ability- and PLA2-dependent fashions during
      cultivation after M. tuberculosis infection. FFA, RNI and H2O2-mediated
      halogenation system (H2O2-halogenation system) displayed strong activity against
      M. tuberculosis in cell-free systems, while ROI alone exerted no such effects.
      Combinations of 'FFA + RNI' and 'RNI + H2O2-halogenation system' exhibited
      synergistic and additive effects against M. tuberculosis, respectively, while
      'FFA + H2O2-halogenation system' had an antagonistic effect. Moreover, a
      sequential attack of FFA followed by RNI exerted synergistic activity against M.
      tuberculosis. Since M. tuberculosis-infected macrophages showed simultaneous
      production of RNI with FFA secretion for relatively long periods (approx. 45 h)
      and prolonged RNI production was seen thereafter, RNI in combination with FFA
      appear to play critical roles in the manifestation of the activity of macrophages
      against M. tuberculosis.

PMID- 10931147
TI  - Dysregulation in IL-12 secretion by neutrophils from HIV-infected patients.
AB  - It is generally believed that neutrophils from HIV-infected patients are
      functionally competent, but several studies have shown impairment in neutrophil
      fungal killing and cytokine production. In this study we evaluated the ability of
      neutrophils from healthy donors and HIV-infected patients to produce IL-12 in
      response to stimulation with Candida albicans, lipopolysaccharide (LPS) and
      Cryptococcus neoformans (acapsular and encapsulated), with and without MoAb
      opsonization. Neutrophils from healthy donors secreted IL-12 in response to LPS
      or C. albicans but not in response to encapsulated or acapsular C. neoformans,
      regardless of MoAb opsonization. Surprisingly, neutrophils from HIV-infected
      patients demonstrated constitutive IL-12 production, although these cells were
      not responsive to LPS stimulation. The inability of MoAb to C. neoformans
      capsular polysaccharide to promote IL-12 production by neutrophils excludes
      phagocytosis and/or CD16 cross-linking in this process, and distinguishes
      neutrophils from monocytes. Our results provide additional evidence for cytokine
      dysregulation in neutrophils from HIV-infected patients. Furthermore, the IL-12
      response of neutrophils and monocytes to CD16 stimulation appears to be
      different, suggesting differences in the role of these phagocytic cells during
      the inflammatory response.

PMID- 10931148
TI  - High levels of IL-10 and determination of other cytokines and chemokines in HIV
      associated haemophagocytic syndrome.
AB  - Haemophagocytic syndrome (HPS) and HIV infection are both associated with
      cytokine network dysregulation. We therefore analysed plasma levels and mRNA
      synthesis in peripheral blood mononuclear cells (PBMC) of cytokines, chemokines
      and chemokine receptors in one HIV-infected patient with HPS. We compared the
      results with those for eight HIV-infected patients with similar CD4+ T cell
      counts (207/mm3 versus controls: median 214/mm3) and plasma virus load (4.1 log
      copies/ml, versus controls: median 4.2 log copies/ml). The HPS patient had a
      lower viral DNA load in PBMC and higher plasma levels of interferon-gamma, IL-10,
      and macrophage inflammatory protein (MIP)-1beta. No difference in plasma tumour
      necrosis factor-alpha (TNF-alpha), IL-6 and MIP-1alpha concentration was observed
      between the HPS patient and control patients. No difference was observed in TNF
      alpha, IL-1beta, IL-10, IL-4, MIP-1alpha, MIP-1beta, RANTES, CXCR-4, and CCR-5
      mRNA levels in PBMC, but IL-6 levels were higher in the HPS patient. Our results
      emphasize the role of IL-10 in the control of immune hyperactivation that is
      observed in HPS.

PMID- 10931149
TI  - Expression of MHC class II in T cells is associated with increased HIV-1
      expression.
AB  - HIV-1 replicates in activated T cells at significantly higher levels than in
      resting cells. Thus, certain molecules up-regulated during T cell activation
      appear to be important for HIV-1 replication. In this study, we present evidence
      suggesting that expression of MHC class II (class II) molecules on CD4+ T cells
      facilitate HIV-1 replication. T cells that expressed class II supported greater
      virus replication than T cells lacking class II. The class II+ cells, when either
      infected with HIV-1 or transfected with an env-minus HIV-1 provirus plasmid,
      produced 10-20-fold greater virus expression than class II- cells. Anti-class II
      antibody markedly inhibited virus expression in class II+ cells (but not class II
      cells) and also decreased the nuclear binding activity of AP-1, an inducible
      transcription factor important in T cell activation and HIV-1 expression. Most
      importantly, the induction of class II expression by transfection of the MHC
      class II transactivator (CIITA) stimulated HIV-1 replication in Jurkat T cells.
      Taken together, these data suggest that expression of MHC class II molecules
      and/or CIITA in T cells enhances HIV-1 transcription.

PMID- 10931150
TI  - Predominant type-2 response in infants with respiratory syncytial virus (RSV)
      infection demonstrated by cytokine flow cytometry.
AB  - Acute RSV infection in infancy may produce some asthma-like symptoms and may be
      followed by a recurrent wheeze later in childhood. It has been proposed that RSV
      infection stimulates type-2 cytokine responses, resembling those found in atopy
      and asthma. Peripheral blood cells were obtained from RSV-infected infants (n =
      30) and healthy controls (n = 10). After in vitro restimulation of the cells,
      intracellular IL-4 and interferon-gamma (IFN-gamma) were measured by flow
      cytometry. The cells from RSV-infected infants produced more IL-4 and less IFN
      gamma than those from healthy controls. IL-4 production was more frequent in CD8
      than in CD4 cells, and the bias toward IL-4 production was greatest in infants
      with mild infections, whereas IFN-gamma production increased with disease
      severity. Our conclusions are that RSV infection is associated with IL-4
      production in peripheral T cells, and that peripheral blood in infants with
      severe disease may be depleted of cytokine-producing cells.

PMID- 10931151
TI  - Expression of intercellular adhesion molecule-1 (ICAM-1) in nasal epithelial
      cells of atopic subjects: a mechanism for increased rhinovirus infection?
AB  - Since clinical experimental studies indicate that upper respiratory tract viral
      infections may exacerbate acute asthma symptoms in atopic/asthmatic individuals,
      we have investigated the expression and modulation of ICAM-1 on human nasal
      epithelial cells (HNEC) from normal and atopic subjects. ICAM-1 is the attachment
      molecule for the majority of serotypes of human rhinovirus (HRV), including HRV
      14, and is also critical for the migration and activation of immune effector
      cells. Basal ICAM-1 expression was significantly higher in HNEC obtained by
      brushings from atopic compared with non-atopic subjects (P = 0.031), and was also
      significantly increased on atopic HNEC harvested in season compared with out of
      season (P < 0.05). Atopic HNEC showed further up-regulation in ICAM-1 expression
      when cultured with clinically relevant allergen (P = 0.032). ICAM-1 levels on
      normal HNEC were also increased by infection with HRV-14 (P < 0.05). Basal
      expression of ICAM-1 on atopic nasal polyp epithelial cells (EC) was
      significantly higher than on both normal and atopic nasal HNEC. This elevated
      nasal polyp ICAM-1 level was not increased further by allergen, although HRV
      infection resulted in a small significant increase. Recovered viral titres from
      HRV-infected nasal polyp EC were 1.5-fold higher than from infected normal nasal
      HNEC. The data are consistent with the hypothesis that allergen, by enhancing
      expression of the HRV attachment target on host cells, facilitates viral
      infection in atopic subjects; simultaneously HRV-induced increases in ICAM-1
      levels would favour migration and activation of immune effector cells to the
      airway, resulting in enhanced atopic inflammation.

PMID- 10931152
TI  - Absence of CD40-CD40 ligand interactions in X-linked hyper-IgM syndrome does not
      affect differentiation of T helper cell subsets.
AB  - The aim of this study was to investigate the effect of absent CD40-CD40 ligand
      interactions in patients with X-linked hyper-IgM syndrome (XHIGM) on the
      generation of Th1 and Th2 immunity. Whole blood from patients and sex- and age
      matched controls was stimulated with phorbol myristate acetate (PMA) and calcium
      ionophore A23187 in the presence of Brefeldin A. After 5 h, cellular production
      of interferon-gamma, IL-4, tumour necrosis factor-alpha and IL-2 was measured by
      intracellular cytokine staining and flow cytometry. This method has been shown
      previously to preferentially activate memory T cells and in preliminary
      experiments cells making these cytokines were found to be predominantly CD45RO+.
      No differences in the proportion of T cells (CD3+) or T cell subsets (CD4+/CD8+)
      secreting these cytokines between XHIGM patients and age- and sex-matched
      controls were observed. In addition, production of IL-12 and IL-6 by monocytes in
      response to lipopolysaccharide and CD40 stimulation was equivalent in patients
      and controls. These results suggest that development of Th1 or Th2 memory cells
      in patients with XHIGM is unaffected by the absence of functional CD40 ligand.
      Rather, the susceptibility of these patients to intracellular pathogens, such as
      Pneumocystis carinii and Cryptosporidium parvum, is more likely to be due to an
      inability to activate the effector arm of the cellular immune response.

PMID- 10931153
TI  - Cytomegalovirus infection in infants with autoimmune lymphoproliferative syndrome
      (ALPS).
AB  - Fas-mediated apoptosis may be one of the effector pathways leading to the
      elimination of virus-infected cells. Cytomegalovirus (CMV) infection in two
      brothers with Fas deficiency associated with autoimmunity and benign
      lymphoproliferation (ALPS) provided a unique opportunity to study the clinical
      course of CMV infection in children with defective apoptosis. The clinical
      courses of two brothers with autosomal dominant ALPS who were infected with CMV
      in the neonatal period are described. CMV was detected from throat and urine
      culture from the brothers. ALPS was confirmed by in vitro anti-CD95 MoAb-induced
      T lymphocyte apoptosis assay and subsequent sequencing and identification of
      mutations in the Fas gene. A de novo mutation in the Fas gene, leading to a
      truncated cytoplasmic Fas product, was associated with autosomal dominant ALPS in
      a mother and her two sons. Both boys had evidence of CMV infection acquired early
      in infancy which cleared by the age of 2-3 years. There were no
      neurodevelopmental sequelae. The natural history of CMV infection in two infants
      with ALPS was similar to that described in normal children.

PMID- 10931154
TI  - Antibody from mice immunized with DNA encoding the carboxyl-disintegrin and
      cysteine-rich domain (JD9) of the haemorrhagic metalloprotease, Jararhagin,
      inhibits the main lethal component of viper venom.
AB  - Envenoming by the Brazilian pit viper, Bothrops jararaca, induces extensive local
      and systemic haemorrhage in humans. The severe and occasionally lethal outcome of
      envenoming is prevented only by administration of antivenom which is
      conventionally prepared by hyperimmunization of large animals with an individual
      venom or a range of venoms. Since snake venoms typically consist of numerous
      molecules, only some of which are toxic, antivenoms are antigenically crude
      preparations whose therapeutic value would theoretically be enhanced by
      restricting antibody specificity to toxic venom molecules. We report here that
      high-titre IgG antibody from mice immunized by the GeneGun with DNA encoding the
      carboxy-terminal JD9 domain of Jararhagin, a haemorrhage-inducing metalloprotease
      in B. jararaca venom, extensively neutralized the main lethal component of B.
      jararaca venom. This is to our knowledge the first study to apply DNA-based
      methods to preparation of antivenom; it represents a novel approach with greater
      immunological specificity and fewer hazards than conventional systems of
      antivenom production.

PMID- 10931155
TI  - Isolation and characterization of cDNA encoding the antigenic protein of the
      human tRNP(Ser)Sec complex recognized by autoantibodies from patients withtype-1
      autoimmune hepatitis.
AB  - We previously described autoantibodies against a UGA serine tRNA-protein complex
      (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define
      the specificity and frequency of this autoantibody and the DNA sequence encoding
      the tRNA(Ser)Sec-associated antigenic protein. The presence of anti-tRNP(Ser)Sec
      antibodies was highly specific for type-1 autoimmune hepatitis, as 47.5% of
      patients were positive compared with none of the control subjects. To
      characterize the antigenic protein(s), we immunoscreened a human cDNA library
      with anti-tRNP(Ser)Sec-positive sera. Two clones (19 and 13) were isolated. Clone
      19 encodes a protein with a predicted molecular mass of 48.8 kD. Clone 13 is a
      shorter cDNA, almost identical to clone 19, which encodes a 35.9-kD protein.
      Expression of both cDNAs was accomplished in Escherichia coli as His-tagged
      recombinant proteins. Antibodies eluted from both purified recombinant proteins
      were able to immunoprecipitate the tRNA(Ser)Sec from a HeLa S3 cell extract,
      demonstrating their cross-reactivity with the mammalian antigenic complex. Recent
      cloning data relating to the target antigen(s) of autoantibodies in autoimmune
      hepatitis patients that react with a soluble liver antigen (SLA) and a liver
      pancreas antigen (LP) have revealed that these two autoantibodies are identical
      and that the cloned antigen shows 99% amino acid sequence homology with
      tRNP(Ser)Sec.

PMID- 10931156
TI  - Blockade of leucocyte function-associated antigen-1 (LFA-1) decreases lymphocyte
      trapping in the normal pulmonary vasculature: studies in the isolated buffer
      perfused rat lung.
AB  - Adhesion molecules regulate the migration of lymphocytes in lymphoid and non
      lymphoid organs. In the lung, little is known about lymphocyte sticking and
      migration through the pulmonary vascular endothelium in physiological or
      pathological situations. Therefore the isolated buffer-perfused rat lung was used
      to investigate the mobilization of lymphocytes out of the normal lung into the
      venous effluent and to the bronchoalveolar space. The lymphocyte subset
      composition was characterized in the venous effluent, the lung tissue and the
      bronchoalveolar lavage (BAL) using immunocytology. Lymphocytes continuously left
      the normal lung at a total of 5.0 +/- 0.7 x 106 cells within the first hour of
      perfusion. The injection of 200 x 106 lymphocytes via the pulmonary trunk
      increased the venous release of lymphocytes by 170%. To investigate the effect of
      LFA-1 and CD44 on the adhesion of lymphocytes to the pulmonary endothelium,
      lymphocytes preincubated with an anti-LFA-1 MoAb, which blocks the interaction of
      LFA-1 and intercellular adhesion molecule-1 (ICAM-1), or lymphocytes preincubated
      with an anti-CD44 MoAb, were injected. The injection of LFA-1-blocked lymphocytes
      led to an increase by 70% of injected cells recovered in the perfusate within the
      first hour, whereas anti-CD44 treatment of injected lymphocytes had no effect.
      The LFA-1-blocked lymphocytes showed higher numbers of T and B cells in the
      effluent. Thus, the present experiments demonstrate that LFA-1 influences the
      trapping of lymphocytes in the vasculature of the healthy rat lung.

PMID- 10931157
TI  - The differential effect of stress on natural killer T (NKT) and NK cell function.
AB  - When C57Bl/6 mice were exposed to restraint stress for 12 h or 24 h,
      lymphocytopenia was induced in the liver, spleen, and thymus. We examined which
      types of lymphocytes were sensitive or resistant to such stress by a
      immunofluorescence test. T cells of thymic origin were sensitive while NKT and NK
      cells were resistant. In contrast to the increase in the proportion of NK cells,
      NK activity of liver lymphocytes against YAC-1 targets decreased at 24 h after
      stress. On the other hand, their NKT cytotoxicity against syngeneic thymocytes
      increased in parallel with an increase in their proportion. In perforin -/- B6
      mice and B6-gld/gld (Fas ligand-) mice, NK cells were found to mediate
      cytotoxicity through perforin while NKT cells mediated self-reactive cytotoxicity
      through Fas ligand. These results suggest that stress increases the proportion of
      both NK and NKT cells, but that NK cytotoxicity is suppressed while self-reactive
      NKT cytotoxicity is not, due to a diversity of their functional mechanisms.

PMID- 10931158
TI  - Cyclosporin A reduces expression of adhesion molecules in the kidney of rats with
      chronic serum sickness.
AB  - Treatment with cyclosporin A (CsA) improves proteinuria and reduces renal
      cellular infiltration in chronic serum sickness (CSS). We examined if these
      effects were associated with a reduced renal expression of CD54 and its ligands,
      interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and MHC
      class II molecules. We studied two groups of rats in which CSS was induced by
      daily injections of ovalbumin (OVA): a group treated with CsA (OVA.CsA group, n =
      11) and a group that received no treatment (OVA.CSS group, n = 11). An additional
      group of five rats (control group) received only phosphate buffer. Immunostaining
      techniques were used to follow CSS and to study the expression of CD54, CD18,
      CD11b/c, IFN-gamma, TNF-alpha and MHC class molecules. Proteinuria (mg/24 h) was
      reduced from 248.2 +/- 73.1 (OVA.CCS group) to 14.5 +/- 13.1 with CsA treatment
      (P < 0.0001). The renal expression of CD54 and its ligands (CD18 and CD11b/c) was
      reduced by 50% to 75%. Correspondingly, there was a 60% to 85% reduction in the
      number of infiltrating leucocytes. The number of cells expressing TNF-alpha, IFN
      gamma and MHC II molecules was also reduced. CsA reduces expression of CD54 and
      its ligands. This effect is associated with a reduction of cellular infiltration,
      IFN-gamma, TNF-alpha-producing cells and with MHC II expression in the kidney.
      These findings suggest that expression of adhesion molecules plays a critical
      role in CSS and underline the importance of cellular immunity in this
      experimental model.

PMID- 10931159
TI  - Widespread susceptibility among inbred mouse strains to the induction of lupus
      autoantibodies by pristane.
AB  - Unlike other agents associated with drug-induced lupus, the isoprenoid alkane
      pristane induces autoantibodies pathognomonic of lupus, including anti-Sm, anti
      dsDNA, and anti-ribosomal P in BALB/c and SJL/J mice. The susceptibility of other
      strains of mice to pristane-induced lupus is unknown and is the focus of the
      present study. Anti-nRNP/Sm, anti-Su, and anti-ribosomal P autoantibodies were
      produced by most strains of mice surveyed within several months of pristane
      treatment, although there was marked interstrain variability in their
      frequencies, levels, and times of onset. In sharp contrast, the production of
      autoantibodies against the double-stranded RNA binding proteins NF45/NF90/p110
      was restricted to B6 and B10.S mice. We conclude that pristane selectively
      induces lupus-specific autoantibodies in virtually any strain of mouse regardless
      of its genetic background. However, H-2-linked as well as non-H2 genes influenced
      the expression of individual autoantibody markers. The widespread susceptibility
      of pristane-treated mice to lupus autoantibody production and the relatively
      small effect of MHC are unique features of this chemically induced lupus
      syndrome, with potential implications for understanding the pathogenesis of
      autoantibodies in idiopathic human systemic lupus erythematosus.

PMID- 10931161
TI  - Hyperhomocysteinemia and thrombosis.
AB  - It has been known for some time that patients with homocystinuria are at an
      increased risk for both venous and arterial thrombosis. More recently it has been
      found that even moderate increases in homocysteine levels are associated with
      increased risk for deep venous thrombosis, myocardial infarction, cerebral
      infarction and peripheral vascular disease. It is possible, with the use of folic
      acid, vitamin B12 and vitamin B6, to correct the elevated homocysteine levels but
      it has not yet been demonstrated that by doing so the natural history of the
      disorder is altered.

PMID- 10931162
TI  - Palpable splenomegaly in children with haemoglobin SC disease: haematological and
      clinical manifestations.
AB  - This study aimed to investigate the prevalence of palpable splenomegaly in
      children with haemoglobin SC (Hb SC) disease, and to determine the haematological
      and clinical manifestations of splenomegaly in this patient population. We
      performed a retrospective chart review of 100 patients with Hb SC over 2 years of
      age followed by the Duke University Paediatric Sickle Cell Program with serial
      physical examinations and laboratory measurements. Palpable splenomegaly was
      present in 34% of patients and was more common in males (P = 0.029). Children
      with splenomegaly had a significantly lower average haemoglobin concentration
      (10.3 vs. 10.8 g/dl, P = 0.011) and lower platelet count (237 vs. 314 x 109/l, P
      < 0.001) than those without splenomegaly. Children with measurements both before
      and after the onset of splenomegaly had a significant decrease in the platelet
      count (279 vs. 216 x 109/l, P < 0.001) and white blood cell count (9.1 vs. 7.9 x
      109/l, P = 0.04) after splenomegaly was identified. Clinical complications
      included acute splenic sequestration in 12% of children (median age 5.4 years),
      and hypersplenism with chronic thrombocytopenia in another 10% of patients
      (median age 10.6 years). Splenomegaly is a common physical finding in children
      with Hb SC disease and is often associated with mild cytopenias. Clinical
      complications of splenomegaly include acute splenic sequestration in younger
      patients and hypersplenism with chronic thrombocytopenia in older children.

PMID- 10931160
TI  - Different regulation of factor H and FHL-1/reconectin by inflammatory mediators
      and expression of the two proteins in rheumatoid arthritis (RA).
AB  - Factor H and the FHL-1/reconectin protein are two human plasma proteins that act
      as important regulators of the alternative complement pathway. Each protein is
      encoded by a unique transcript, but both mRNAs are derived from the factor H gene
      by means of alternative processing. In order to address potential functional
      differences between the two proteins we analysed their expression in hepatic and
      non-hepatic cells and studied their regulation by inflammatory mediators. We
      demonstrate that factor H and FHL-1/reconectin transcripts which are regulated by
      the same gene promoter and are initiated at the same transcription start site are
      differently expressed. Expression of the molecules is induced and regulated by
      the inflammatory mediators interferon-gamma (IFN-gamma) and the anti-inflammatory
      glucocorticoid dexamethasone. Both factor H and FHL-1/reconectin are expressed
      and secreted by synovial fibroblasts and are present in synovial fluid derived
      from patients suffering from rheumatoid or reactive arthritis. The local
      synthesis in synovial fibroblasts and their induction by IFN-gamma and
      dexamethasone, but not by tumour necrosis factor-alpha, suggests for each of the
      two complement regulators a protective role in RA.

PMID- 10931163
TI  - Acute sickle cell syndromes in Nigerian adults.
AB  - The pattern of acute illness was determined in 102 adolescents and adults with
      sickle cell anaemia who presented to the emergency unit of a Lagos hospital. The
      patients had a mean age of 20.5 years (SD 13.1) and a male-female ratio of 1.5.
      The symptoms included fever (72%), fatigue and weakness (59%), anorexia (59%) and
      pain (57.5%) while major clinical signs were pallor (100%), jaundice (71%) and
      hepatomegaly (68%). Sixty-eight per cent of patients had sickle cell crises,
      including one with hemiplegic stroke, 10% with combined anaemia and pain crises,
      33% with anaemia crises only and 23.5% with pain crises only. Sixty-three per
      cent had infection which was malaria in 24.5%, bacterial in 17% and viral in 6%.
      Of 16 patients with pyrexia of unknown origin, seven responded to treatment with
      chloroquine and eight to antibiotics. Infection was detected in 50% of the
      patients with sickle cell crises. The association between anaemia crises and
      malaria was significant (P < 0.05). Of the eight deaths, seven (88%) had anaemia
      crises. In contrast to studies conducted two decades ago in the same hospital,
      the prevalence of anaemia crises now exceeds that of pain crises and malaria now
      exceeds that of bacterial infection. Severe symptomatic anaemia (anaemia crisis)
      was more frequently associated with infection (mostly malaria) than was bone pain
      crisis. The Girdle pain crisis more frequently resulted in a fatal outcome than
      the uncomplicated bone pain crisis.

PMID- 10931164
TI  - An audit of delays in diagnosis and treatment of lymphoma in district hospitals
      in the northern region of the United Kingdom.
AB  - Prompt diagnosis and treatment of malignant disorders is generally regarded as
      improving outcomes. There is good evidence for this in the most common solid
      tumours, bronchus, breast and large bowel. It might be expected that delays in
      diagnosis of lymphoma could affect the outcome of treatment, as well as causing
      dissatisfaction among patients and relatives. However it would be difficult to
      obtain definite evidence for this as a randomised trial of delay is an unethical
      proposition. The recently introduced National Priorities Guidance (NPG) Cancer
      Targets require that all new patients with suspected cancer should see a
      specialist within two weeks of referral by their General Practitioner (GP). There
      is no good evidence to support this requirement in lymphoma, but we decided to
      audit delays at different stages of the process of diagnosis and initial
      treatment of lymphoma as a base line to assess current performance, identify
      possible shortcomings and set achievable standards amenable to further audit.

PMID- 10931165
TI  - Essential thrombocythemia and recurrent myocardial infarction.
AB  - We report the case of recurrent myocardial infarction with essential
      thrombocythemia (ET) in a 61-year-old female patient. Only one report of
      recurrence of myocardial infarction has been previously described. Coronary
      angiography 10 days after the infarction was normal. Thrombocythemia had been
      controlled with hydroxyurea.

PMID- 10931166
TI  - Acquired haemophilia complicating the remission of a patient with high grade non
      Hodgkin's lymphoma treated by fludarabine.
AB  - We report the development of a high titre antibody to factor VIII in a patient
      with previous high grade B cell non-Hodgkin's lymphoma treated with fludarabine.
      Unlike previous reports of factor VIII inhibitors and lymphoproliferative disease
      this patient's lymphoma was in remission. We speculate that the occurrence of the
      inhibitor is another manifestation of the increasingly recognized autoimmune side
      effects of fludarabine.

PMID- 10931167
TI  - Amiodarone-induced bone marrow granulomas.
AB  - Amiodarone hydrochloride, a class III antiarrhythmic agent used to treat
      supraventricular and ventricular cardiac dysrhythmias. In this report we describe
      two patients receiving amiodarone for atrial fibrillation who underwent bone
      marrow biopsies to investigate paraproteinaemia (case 1) or severe
      thrombocytopenia (case 2). Multiple bone marrow granulomas were found in both
      patients, without evidence of any other cause. In both patients the granulomas
      disappeared after amiodarone withdrawal, suggesting a direct association.

PMID- 10931168
TI  - Scrotal ulceration during all-trans retinoic (ATRA) therapy for acute
      promyelocytic leukaemia.
AB  - We report the development of painful scrotal ulceration in two patients during
      treatment with all-trans-retinoic acid (ATRA) for acute promyelocytic leukaemia
      (APL). ATRA 45 mg/m2 was administered orally for 8 days prior to the addition of
      standard induction chemotherapy. Painful scrotal ulceration developed in both
      cases within 2 weeks of therapy (9 and 13 days) and responded slowly to drug
      withdrawal and systemic, or topical, corticosteroids. A total of 17 APL patients
      have been treated with ATRA at our institution during the last 10 years, giving
      an incidence of approximately 12%. The present report, together with a review of
      literature, suggests that scrotal ulceration is a specific adverse effect of ATRA
      therapy and that this complication may be more common than previously documented.

PMID- 10931169
TI  - Autoimmune thrombocytopenia: a complication of fludarabine therapy in
      lymphoproliferative disorders.
AB  - We describe two cases of autoimmune thrombocytopenia precipitated by fludarabine
      therapy in patients with chronic lymphatic leukaemia. Both were treated with high
      dose steroids and initially responded with recovery of normal platelet counts.
      One patient developed recurrent autoimmune thrombocytopenia on two occasions
      following re-exposure to the drug when his disease had become refractory to all
      other treatments. A retrospective review of the case notes of 45 patients with
      lymphoproliferative disorders treated with fludarabine over the past 6 years
      indicated the development of autoimmune thrombocytopenia in 4.5% (two out of 45)
      and autoimmune haemolytic anaemia in 6.7% (three of the 45).

PMID- 10931170
TI  - Virus-associated haemophagocytic syndrome responsive to steroid pulse therapy and
      double filtration plasmapheresis.
AB  - We present an adult patient with haemophagocytic syndrome (HPS) successfully
      treated with a combination of steroid pulse therapy and double filtration
      plasmapheresis (DFPP). A 58-year-old male was admitted with high fever, severe
      renal dysfunction, liver dysfunction and an increased level of lactate
      dehydrogenase. A serological test for Epstein-Barr (EB) virus showed an elevation
      of EBNA-IgM antibody titre. There were increased haemophagocytic histiocytes in
      the bone marrow in addition to thrombocytopenia and disseminated intravascular
      coagulation (DIC) accompanied by organ dysfunction. EB virus associated
      haemophagocytic syndrome was diagnosed. On admission, interferon (IFN)-gamma,
      interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and
      macrophage (M)-CSF were elevated, and were promptly normalized after steroid
      pulse therapy was initiated. G-CSF and M-CSF gradually decreased after DFPPs was
      started. To control hypercytokinaemia until treatment for the underlying disease
      is initiated, steroid pulse therapy and double filtration plasmapheresis are
      useful.

PMID- 10931171
TI  - Glutathione metabolism and oxidative stress in neurodegeneration

PMID- 10931172
TI  - Glutathione, oxidative stress and neurodegeneration.
AB  - There is significant evidence that the pathogenesis of several neurodegenerative
      diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia
      and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen
      species and mitochondrial dysfunction. Here, we review the evidence for a
      disturbance of glutathione homeostasis that may either lead to or result from
      oxidative stress in neurodegenerative disorders. Glutathione is an important
      intracellular antioxidant that protects against a variety of different
      antioxidant species. An important role for glutathione was proposed for the
      pathogenesis of Parkinson's disease, because a decrease in total glutathione
      concentrations in the substantia nigra has been observed in preclinical stages,
      at a time at which other biochemical changes are not yet detectable. Because
      glutathione does not cross the blood-brain barrier other treatment options to
      increase brain concentrations of glutathione including glutathione analogs,
      mimetics or precursors are discussed.

PMID- 10931173
TI  - Glutathione metabolism in brain metabolic interaction between astrocytes and
      neurons in the defense against reactive oxygen species.
AB  - The cells of the adult human brain consume approximately 20% of the oxygen
      utilized by the body although the brain comprises only 2% of the body weight.
      Reactive oxygen species, which are produced continuously during oxidative
      metabolism, are generated at high rates within the brain. Therefore, the defense
      against the toxic effects of reactive oxygen species is an essential task within
      the brain. An important component of the cellular detoxification of reactive
      oxygen species is the antioxidant glutathione. The main focus of this short
      review is recent results on glutathione metabolism of brain astrocytes and
      neurons in culture. These two types of cell prefer different extracellular
      precursors for glutathione. Glutathione is involved in the disposal of exogenous
      peroxides by astrocytes and neurons. In coculture astrocytes protect neurons
      against the toxicity of reactive oxygen species. One mechanism of this
      interaction is the supply by astrocytes of glutathione precursors to neurons.

PMID- 10931174
TI  - Comparative biology of the endocannabinoid system possible role in the immune
      response.
AB  - In this review we discuss data showing that the endogenous cannabinoid system,
      represented by cannabinoid receptors, endogenous cannabinoid receptor ligands and
      enzymes for the biosynthesis and degradation of these ligands, is conserved
      throughout evolution from coelenterates to man. This signaling system has been
      suggested to play several roles in animals, including the regulation of cell
      development and growth, nervous functions, reproduction and feeding behavior. In
      this article, however, we shall describe with more detail the possible function
      of the endogenous cannabinoid system in the modulation of immune response in
      organisms from the lower to the higher levels of animal evolution.

PMID- 10931175
TI  - Regulation of protein function by S-glutathiolation in response to oxidative and
      nitrosative stress.
AB  - Protein S-glutathiolation, the reversible covalent addition of glutathione to
      cysteine residues on target proteins, is emerging as a candidate mechanism by
      which both changes in the intracellular redox state and the generation of
      reactive oxygen and nitrogen species may be transduced into a functional
      response. This review will provide an introduction to the concepts of oxidative
      and nitrosative stress and outline the molecular mechanisms of protein regulation
      by oxidative and nitrosative thiol-group modifications. Special attention will be
      paid to recently published work supporting a role for S-glutathiolation in stress
      signalling pathways and in the adaptive cellular response to oxidative and
      nitrosative stress. Finally, novel insights into the molecular mechanisms of S
      glutathiolation as well as methodological problems related to the interpretation
      of the biological relevance of this post-translational protein modification will
      be discussed.

PMID- 10931176
TI  - Sequence diversification of the FK506-binding proteins in several different
      genomes.
AB  - Sequences of FK506-binding proteins (FKBPs) from four genomes of the following
      organisms were compared: the prokaryote Escherichia coli, the lower eukaryote
      Saccharomyces cerevisiae, the plant Arabidopsis thaliana, the nematode
      Caenorhabditis elegans and a composite of 14 unique FKBPs from two mammalian
      organisms Homo sapiens (man) and Mus musculus (domestic mouse). A singular FK506
      like binding domain (FKBD) has about 12 kDa and occurs in the form of archetypal
      FKBP-12 and as a part of different proteins ranging in size from 13 to 135 kDa.
      Some organisms may contain a variable number of proteins which consist from two
      to four consecutively fused FKBDs. In the 12-kDa subgroup of archetypal FKBPs
      sequence identity (ID) varies from 100 to 83% (mammalian FKBPs-12), 75-50% in
      mammalian vs. invertebrate FKBPs-12, and fall to about 30% for pairwise sequence
      comparisons of mammalian and bacterial FKBPs-12 which suggests that their
      sequences are divergent. Multiple sequence alignment of FKBPs from the four
      genomes and a set of unique mammalian FKBPs does not contain any explicit
      consensus sequence but certain sequence positions have conserved physico-chemical
      characteristics. Variations of hydrophobicity and bulkiness in the multiple
      sequence alignment are nonsymmetrical because the physico-chemical properties of
      the aligned sequences changed during evolution. These variations at the sequence
      positions which are crucial for binding the immunosuppressive macrolide FK506 and
      peptidyl-prolyl cis/trans isomerase (PPIase) activity are small.

PMID- 10931177
TI  - Basic residues of human group IIA phospholipase A2 are important for binding to
      factor Xa and prothrombinase inhibition comparison with other mammalian secreted
      phospholipases A2.
AB  - Human secreted group IIA phospholipase A2 (hGIIA) was reported to inhibit
      prothrombinase activity because of binding to factor Xa. This study further shows
      that hGIIA and its catalytically inactive H48Q mutant prolong the lag time of
      thrombin generation in human platelet-rich plasma with similar efficiency,
      indicating that hGIIA exerts an anticoagulant effect independently of
      phospholipid hydrolysis under ex vivo conditions. Charge reversal of basic
      residues on the interfacial binding surface (IBS) of hGIIA leads to decreased
      ability to inhibit prothrombinase activity, which correlates with a reduced
      affinity for factor Xa, as determined by surface plasmon resonance. Mutation of
      other surface-exposed basic residues, hydrophobic residues on the IBS, and His48,
      does not affect the ability of hGIIA to inhibit prothrombinase activity and bind
      to factor Xa. Other basic, but not neutral or acidic, mammalian secreted
      phospholipases A2 (sPLA2s) exert a phospholipid-independent inhibitory effect on
      prothrombinase activity, suggesting that these basic sPLA2s also bind to factor
      Xa. In conclusion, this study demonstrates that the anticoagulant effect of hGIIA
      is independent of phospholipid hydrolysis and is based on its interaction with
      factor Xa, leading to prothrombinase inhibition, even under ex vivo conditions.
      This study also shows that such an interaction involves basic residues located on
      the IBS of hGIIA, and suggests that other basic mammalian sPLA2s may also inhibit
      blood coagulation by a similar mechanism to that described for hGIIA.

PMID- 10931178
TI  - Purification, characterization and amino-acid sequence analysis of a
      thermostable, low molecular mass endo-beta-1,4-glucanase from blue mussel,
      Mytilus edulis.
AB  - A cellulase (endo-beta-1,4-D-glucanase, EC 3.2.1.4) from blue mussel (Mytilus
      edulis) was purified to homogeneity using a combination of acid precipitation,
      heat precipitation, immobilized metal ion affinity chromatography, size-exclusion
      chromatography and ion-exchange chromatography. Purity was analyzed by SDS/PAGE,
      IEF and RP-HPLC. The cellulase (endoglucanase) was characterized with regard to
      enzymatic properties, isoelectric point, molecular mass and amino-acid sequence.
      It is a single polypeptide chain of 181 amino acids cross-linked with six
      disulfide bridges. Its molecular mass, as measured by MALDI-MS, is 19 702 Da; a
      value of 19 710.57 Da was calculated from amino-acid composition. The isoelectric
      point of the enzyme was estimated by isoelectric focusing in a polyacrylamide gel
      to a value of 7.6. According to amino-acid composition, the theoretical pI is
      7.011. The effect of temperature on the endoglucanase activity, with
      carboxymethyl cellulose and amorphous cellulose as substrates, respectively, was
      studied at pH 5.5 and displayed an unusually broad optimum activity temperature
      range between 30 and 50 degrees C. Another unusual feature is that the enzyme
      retains 55-60% of its maximum activity at 0 degrees C. The enzyme readily
      degrades amorphous cellulose and carboxymethyl cellulose but displays no
      hydrolytic activity towards crystalline cellulose (Avicel) and shows no cross
      specificity for xylan; there is no binding to Avicel. The enzyme can withstand 10
      min at 100 degrees C without irreversible loss of enzymatic activity. Amino-acid
      sequence-based classification has revealed that the enzyme belongs to the
      glycoside hydrolase family 45, subfamily 2 (B. Henrissat, Centre de Recherches
      sur les Macromolecules Vegetales, CNRS, Joseph Fourier Universite, Grenoble,
      France, personal communication).

PMID- 10931179
TI  - Mass spectrometry study of ecto-5'-nucleotidase from bull seminal plasma.
AB  - The structure of ecto-5'-nucleotidase from bull seminal plasma, containing a
      glycosyl-phosphatidylinositol anchor, was studied using mass spectrometry. MALDI
      MS analysis of intact protein indicated a mass of 65 568.2 Da for the monomeric
      form, and it also showed a heterogeneous population of glycoforms with the
      glycosidic moiety accounting for approximately 6000 Da. MALDI-MS analysis showed
      that Asn53, Asn311, Asn333 and Asn403 were four sites of N-glycosylation. GC-MS
      analysis provided information on the glycosidic structures linked to the four
      asparagines. Asn53, Asn311 and Asn333 were linked to high-mannose saccharide
      chains, whereas the glycan chains linked to Asn403 contained a heterogeneous
      mixture of oligosaccharides, the high-mannose type structure being the most
      abundant and hybrid or complex type glycans being minor components. By combining
      enzymatic and/or chemical hydrolysis with GC-MS analysis, detailed
      characterization of the glycosyl-phpsphatidylinositol anchor was obtained. MALDI
      spectral analysis indicated that the glycosyl-phosphatidylinositol core contained
      EtN(P)Man3GlcNH2-myo-inositol(P)-glycerol, principally modified by stearoyl and
      palmitoyl residues or by stearoyl and myristoyl residues to a minor extent.
      Moreover, 1-palmitoylglycerol and 1-stearoylglycerol outweighed 2
      palmitoylglycerol and 2-stearoylglycerol. The combination of chemical and
      enzymatic digestions of the protein with the mass spectral analysis yielded a
      complete pattern of S-S bridges. The protein does not contain free thiols and its
      eight cysteines are linked by intramolecular disulfide bonds, the pairs being:
      Cys51-Cys57, Cys353-Cys358, Cys365-Cys387 and Cys476-Cys479. This work resolves
      details of the structure of ecto-5'-nucleotidase, with particular regard to the
      localization and composition of the glycidic moiety, number and localization of
      the disulfide bridges and characterization of the glycosyl-phosphatidylinositol
      anchor.

PMID- 10931180
TI  - Cloning, expression and characterization of a family 48 exocellulase, Cel48A,
      from Thermobifida fusca.
AB  - The gene for a 104-kDa exocellulase, Cel48A, formerly E6, was cloned from
      Thermobifida fusca into Escherichia coli and Streptomyces lividans. The DNA
      sequence revealed a type II cellulose-binding domain at the N-terminus, followed
      by a FNIII-like domain and ending with a glycosyl hydrolase Family 48 catalytic
      domain. The enzyme and catalytic domain alone were each expressed in and purified
      from S. lividans and had very low catalytic activity on swollen cellulose,
      carboxymethyl cellulose, bacterial microcrystalline cellulose and filter paper.
      However, in synergistic assays on filter paper, the addition of Cel48A to a
      balanced mixture of T. fusca endocellulase and exocellulase increased the
      specific activity from 7.9 to 11.7 micromol cellobiose.min-1.mL-1, more than 15
      fold higher than any single enzyme alone. Cel48A retained > 50% of its maximum
      activity from pH 5 to 9 and from 40 to 60 degrees C. Using SWISSMODEL, the amino
      acid sequence of the Cel48Acd was modeled to the known structure of Clostridium
      cellulolyticum CelF. Family 48 enzymes are remarkably homologous at 35% identity
      for all their catalytic domains and some of the properties of the 10 members are
      discussed.

PMID- 10931181
TI  - Processing of synthetic pro-islet amyloid polypeptide (proIAPP) 'amylin' by
      recombinant prohormone convertase enzymes, PC2 and PC3, in vitro.
AB  - Islet amyloid polypeptide (IAPP), amylin, is the constituent peptide of
      pancreatic islet amyloid deposits which form in islets of Type 2 diabetic
      subjects. Human IAPP is synthesized as a 67-residue propeptide in islet beta
      cells and colocalized with insulin in beta-cell granules. The mature 37-amino
      acid peptide is produced by proteolysis at pairs of basic residues at the C- and
      N-termini of the mature peptide. To determine the enzymes responsible for
      proteolysis and their activity at the potential cleavage sites, synthetic human
      proIAPP was incubated (0.5-16 h) with recombinant prohormone convertases, PC2 or
      PC3 at appropriate conditions of calcium and pH. The products were analysed by MS
      and HPLC. Proinsulin was used as a control and was cleaved by both recombinant
      enzymes resulting in intermediates. PC3 was active initially at the N-terminal
      IAPP junction and later at the C-terminus, whereas initial PC2 activity was at
      the IAPP-C-terminal junction. Processing at the basic residues within the C
      terminal flanking peptide rarely occurred. There was no evidence for substantial
      competition for the processing enzymes when the combined substrates proinsulin
      and proIAPP were incubated with both PC2 and PC3. As proinsulin cleavage is
      sequential in vivo (PC3 active at the B-chain-C-peptide junction, followed by PC2
      at A chain-C-peptide junction), these data suggest that proteolysis of proIAPP
      and proinsulin is coincident in secretory granules and increased proinsulin
      secretion in diabetes could be accompanied by increased production of proIAPP.

PMID- 10931182
TI  - Independent pathways leading to apoptotic cell death, oxidative burst and defense
      gene expression in response to elicitin in tobacco cell suspension culture.
AB  - We characterized pharmacologically the hypersensitive cell death of tobacco BY-2
      cells that followed treatments with Escherichia coli preparations of INF1, the
      major secreted elicitin of the late blight pathogen Phytophthora infestans. INF1
      elicitin treatments resulted in fragmentation and 180 bp laddering of tobacco DNA
      as early as 3 h post-treatment. INF1 elicitin also induced rapid accumulation of
      H2O2 typical of oxidative burst, and the expression of defense genes such as
      phenylalanine ammonia-lyase (PAL) gene at 1 h and 3 h after elicitin treatment,
      respectively. To investigate the involvement of the oxidative burst and/or the
      expression of defense genes in the signal transduction pathways leading to
      hypersensitive cell death, we analyzed the effect of several chemical inhibitors
      of signal transduction pathways on the various responses. The results indicated
      that (a) the cell death required serine proteases, Ca2+ and protein kinases, (b)
      the oxidative burst was involved in Ca2+ and protein kinase mediated pathways,
      but elicitin-induced AOS was neither necessary nor sufficient for cell death and
      PAL gene expression, and (c) the signaling pathway of PAL gene expression
      required protein kinases. These results suggest that the three signal
      transduction pathways leading to cell death, oxidative burst and expression of
      defense genes branch in the early stages that follow elicitin recognition by
      tobacco cells.

PMID- 10931183
TI  - Nicotinamide adenine dinucleotide species in the horseradish peroxidase-oxidase
      oscillator.
AB  - NADH chemistry ancillary to the oscillatory peroxidase-oxidase (PO) reaction has
      been reexamined. Previously, (NAD)2 has been thought of as a terminal, inert
      product of the PO reaction. We now show that (NAD)2 is a central reactant in this
      system. Although we found traces of the dimer after several hours of the PO
      reaction, no accumulation of the dimer occurred, regardless of the reaction time
      or the number of oscillations. (NAD)2 can convert horseradish peroxidase (HRP)
      compound I (CpI) to compound II (CpII) with apparent rate constant (2.7 +/- 0.2)
      x 105 M-1.s-1 and CpII to HRP at 1 x 105 M-1.s-1. Moreover, a reduction of HRP
      compound III (CpIII) to CpI by (NAD)2 occurs with a rate constant faster than 5 x
      106 M-1.s-1. The (NAD)2 reduction of CpIII provides an alternative to the
      reduction by NAD radical suggested by Yokota and Yamazaki. HRP catalyzes
      oxidation of alpha-NADH, not only the beta anomer as previously assumed. Rate
      constants of alpha- and beta-NADH reactions with CpI are (7.4 +/- 0.4) x 105 M
      1.s-1, and (1.7 +/- 0.2) x 105 M-1.s-1, and with CpII are estimated as 5 x 104 M
      1.s-1, and 4 x 104 M-1.s-1. Apparent rate constants of reduction of methylene
      blue (MB) to leuco-methylene blue (MBH) are 3.8 x 104 M-1.s-1 for NADH and 6.4 x
      104 M-1.s-1 for NAD dimer, (NAD)2, while reoxidation of MBH proceeds at (2.1 +/-
      0.2) x 103 M-1.s-1 All the rates were measured in 0.1 M acetate buffer, pH 5.1.

PMID- 10931185
TI  - Towards the selection of phosphorothioate aptamers optimizing in vitro selection
      steps with phosphorothioate nucleotides.
AB  - The high affinity of a given nucleic acid for a protein ligand can be used to
      isolate specific inhibitors of enzymes involved in pathological situations. The
      latter property is the basis of the SELEX (systematic evolution of ligands by
      exponential enrichment) technique. Recently, several potent nucleic acids
      inhibitors of HIV-1 replication have been isolated using the SELEX approach.
      However, phosphodiester oligodeoxynucleotides (PO-ODNs) were not used as
      antiviral agents because of their sensitivity to nucleases. Our goal in this work
      was to explore the possibility of selecting, from a fully substituted
      phosphorothioate library, oligonucleotides having both a strong affinity for HIV
      1 reverse transcriptase (RT) and nuclease resistance. HIV-1 RT initiates in vivo
      reverse transcription from the 3' end of a host tRNALys. Although
      phosphorothioate ODNs (PS-ODNs) have been claimed to bind unspecifically to
      proteins, we have shown previously that an ODN corresponding to the acceptor stem
      of tRNALys was able to inhibit specifically HIV-1 replication in HIV-1 infected
      cells, without showing cytotoxicity up to 10 microM. As the SELEX strategy
      requires 'in vitro' transcription and reverse transcription of the selected DNA,
      we have assayed the available PS precursors as a model system by using PS-dNTPs
      and rNTPs. We have also developed an experimental procedure to optimize the
      incorporation of four PS-dNTPs during the PCR step of the SELEX approach. In the
      course of this work, we have showed that the PS-dGTP is a strong inhibitor of
      thermostable DNA polymerases as well as of HIV-1 RT.

PMID- 10931184
TI  - Hadrurin, a new antimicrobial peptide from the venom of the scorpion Hadrurus
      aztecus.
AB  - A new antimicrobial peptide, hadrurin, was isolated from the venom of the Mexican
      scorpion Hadrurus aztecus, by gel filtration on a Sephadex G-50 column, followed
      by high performance liquid chromatography. It is a basic peptide composed of 41
      amino-acid residues with a molecular mass of 4436 Da, and contains no cysteines.
      A model of the three-dimensional folding of hadrurin is compatible with that of
      an amphipatic molecule with two alpha-helical segments. Hadrurin demonstrates
      antimicrobial activity at low micromolar concentration, inhibiting the growth of
      bacteria such as: Salmonella thyphi, Klebsiella pneumoniae, Enterococcus cloacae,
      Pseudomonas aeruginosa, Escherichia coli and Serratia marscences. It also shows
      cytolytic activity when tested in human erythrocytes. Hadrurin and two analogs (C
      terminal amidated, and all D-enantiomer) were chemically synthesized. They were
      used to study the possible molecular mechanism of action by testing their ability
      to dissipate the diffusion potential of liposomes of different compositions. The
      results obtained indicate that there are no specific receptor molecules for the
      action of hadrurin, and the most probable mechanism is through a membrane
      destabilization activity. It is surmised that hadrurin is used by the scorpion as
      both an attack and defense element against its prey and putative invasive
      microorganisms. It is a unique peptide among all known antimicrobial peptides
      described, only partially similar to the N-terminal segment of gaegurin 4 and
      brevinin 2e, isolated from frog skin. It would certainly be a model molecule for
      studying new antibiotic activities and peptide-lipid interactions.

PMID- 10931186
TI  - Kinetics of the coupled reaction catalysed by a fusion protein of yeast
      mitochondrial malate dehydrogenase and citrate synthase.
AB  - The mechanistic implications of the kinetic behaviour of a fusion protein of
      mitochondrial malate dehydrogenase and citrate synthase have been reanalysed in
      view of predictions based on experimentally determined kinetic parameter values
      for the dehydrogenase and synthase activities of the protein. The results show
      that the time-course of citrate formation from malate in the coupled reaction
      catalysed by the fusion protein can be most satisfactorily accounted for in terms
      of a free-diffusion mechanism when consideration is taken to the inhibitory
      effects of NADH and oxaloacetate on the malate dehydrogenase activity. The effect
      of aspartate aminotransferase on the coupled reaction is likewise fully
      consistent with that expected for a free-diffusion mechanism. It is concluded
      that no tenable kinetic evidence is available to support the proposal that the
      fusion protein catalyses citrate formation from malate by a mechanism involving
      channelling of the intermediate oxaloacetate.

PMID- 10931187
TI  - Echistatin inhibits pp125FAK autophosphorylation, paxillin phosphorylation and
      pp125FAK-paxillin interaction in fibronectin-adherent melanoma cells.
AB  - Echistatin, a snake-venom RGD-containing protein, was previously shown to disrupt
      cell-matrix adhesion by a mechanism that involves the reduction of pp125FAK
      tyrosine phosphorylation levels. The aim of this study was to establish the
      sequence of events downstream pp125FAK dephosphorylation that could be
      responsible for echistatin-induced disassembly of actin cytoskeleton and focal
      adhesions in fibronectin-adherent B16-BL6 melanoma cells. The results obtained
      show that echistatin induces a decrease of both autophosphorylation and kinase
      activity of pp125FAK. One hour of cell exposure to echistatin caused a 39%
      decrease of pp125FAK Tyr397 phosphorylation and a 31% reduction of pp125FAK
      autophosphorylation activity as measured by immune-complex kinase assay.
      Furthermore, 1 h of cell treatment by echistatin produced a 63% decrease of
      paxillin phosphorylation, as well as a reduction in the amount of paxillin bound
      to pp125FAK. Immunofluorescence analysis of echistatin treated cells showed the
      concomitant disappearance of both paxillin and pp125FAK from focal adhesions. The
      reduction of paxillin phosphorylation may represent a critical step in the
      pathway by which disintegrins exert their biological activity, including the
      inhibition of experimental metastasis in vivo.

PMID- 10931188
TI  - Transgalactosylation by thermostable beta-glycosidases from Pyrococcus furiosus
      and Sulfolobus solfataricus. Binding interactions of nucleophiles with the
      galactosylated enzyme intermediate make major contributions to the formation of
      new beta-glycosides during lactose conversion.
AB  - The hyperthermostable beta-glycosidases from the Archaea Sulfolobus solfataricus
      (SsbetaGly) and Pyrococcus furiosus (CelB) hydrolyse beta-glycosides of D-glucose
      or D-galactose with relaxed specificities pertaining to the nature of the leaving
      group and the glycosidic linkage. To determine how specificity is manifested
      under conditions of kinetically controlled transgalactosylation, the major
      transfer products formed during the hydrolysis of lactose by these enzymes have
      been identified, and their appearance and degradation have been determined in
      dependence of the degree of substrate conversion. CelB and SsbetaGly show a
      marked preference for making new beta(1-->3) and beta(1-->6) glycosidic bonds by
      intermolecular as well as intramolecular transfer reactions. The intramolecular
      galactosyl transfer of CelB, relative to glycosidic-bond cleavage and release of
      glucose, is about 2.2 times that of SsbetaGly and yields beta-D-Galp-(1-->6)-D
      Glc and beta-D-Galp-(1-->3)-D-Glc in a molar ratio of approximately 1 : 2. The
      partitioning of galactosylated SsbetaGly between reaction with sugars [kNu (M-1.
      s-1)] and reaction with water [kwater (s-1)] is about twice that of CelB. It
      gives a mixture of linear beta-D-glycosides, chiefly trisaccharides at early
      reaction times, in which the prevailing new glycosidic bonds are beta(1-->6) and
      beta(1-->3) for the reactions catalysed by SsbetaGly and CelB, respectively. The
      accumulation of beta-D-Galp-(1-->6)-D-Glc at the end of lactose hydrolysis
      reflects a 3-10-fold specificity of both enzymes for the hydrolysis of beta(1-
      >3) over beta(1-->6) linked glucosides. Galactosyl transfer from SsbetaGly or
      CelB to D-glucose occurs with partitioning ratios, kNu/kwater, which are seven
      and > 170 times those for the reactions of the galactosylated enzymes with 1
      propanol and 2-propanol, respectively. Therefore, the binding interactions with
      nucleophiles contribute chiefly to formation of new beta-glycosides during
      lactose conversion. Likewise, noncovalent interactions with the glucose leaving
      group govern the catalytic efficiencies for the hydrolysis of lactose by both
      enzymes. They are almost fully expressed in the rate-limiting first-order rate
      constant for the galactosyl transfer from the substrate to the enzyme and lead to
      a positive deviation by approximately 2.5 log10 units from structure-reactivity
      correlations based on the pKa of the leaving group.

PMID- 10931189
TI  - Cloning and characterization of a monocot mannose-binding lectin from Crocus
      vernus (family Iridaceae).
AB  - The molecular structure and carbohydrate-binding activity of the lectin from
      bulbs of spring crocus (Crocus vernus) has been determined unambiguously using a
      combination of protein analysis and cDNA cloning. Molecular cloning revealed that
      the lectin called C. vernus agglutinin (CVA) is encoded by a precursor consisting
      of two tandemly arrayed lectin domains with a reasonable sequence similarity to
      the monocot mannose-binding lectins. Post-translational cleavage of the precursor
      yields two equally sized polypeptides. Mature CVA consists of two pairs of
      polypeptides and hence is a heterotetrameric protein. Surface plasmon resonance
      studies of the interaction of the crocus lectin with high mannose-type glycans
      showed that the lectin interacts specifically with exposed alpha-1,3-dimannosyl
      motifs. Molecular modelling studies confirmed further the close relationships in
      overall fold and three-dimensional structure of the mannose-binding sites of the
      crocus lectin and other monocot mannose-binding lectins. However, docking
      experiments indicate that only one of the six putative mannose-binding sites of
      the CVA protomer is active. These results can explain the weak carbohydrate
      binding activity and low specific agglutination activity of the lectin. As the
      cloning and characterization of the spring crocus lectin demonstrate that the
      monocot mannose-binding lectins occur also within the family Iridaceae a refined
      model of the molecular evolution of this lectin family is proposed.

PMID- 10931190
TI  - Early activation of lipoxygenase in lentil (Lens culinaris) root protoplasts by
      oxidative stress induces programmed cell death.
AB  - Oxidative stress caused by hydrogen peroxide (H2O2) triggers the hypersensitive
      response of plants to pathogens. Here, short pulses of H2O2 are shown to cause
      death of lentil (Lens culinaris) root protoplasts. Dead cells showed DNA
      fragmentation and ladder formation, typical hallmarks of apoptosis (programmed
      cell death). DNA damage was evident 12 h after the H2O2 pulse and reached a
      maximum 12 h later. The commitment of cells to apoptosis caused by H2O2 was
      characterized by an early increase of lipoxygenase activity, of ultraweak
      luminescence and of membrane lipid peroxidation, which reached 720, 350 and 300%
      of controls, respectively, at 6 h after H2O2 treatment. Increased lipoxygenase
      activity was paralleled by an increase of its protein and mRNA level.
      Lipoxygenase inhibitors nordihydroguaiaretic acid, eicosatetraynoic acid and
      plamitoyl ascorbate prevented H2O2-induced DNA fragmentation and ultraweak
      luminescence, only when added together with H2O2, but not when added 8 h
      afterwards. Inhibitory anti-lipoxygenase monoclonal antibodies, introduced into
      the protoplasts by electroporation, protected cells against H2O2-induced
      apoptosis. On the other hand, lentil lipoxygenase products 9- and 13-hydroperoxy
      octadecadienoic acids and their reduced alcohol derivatives were able to force
      the protoplasts into apoptosis. Altogether, these findings suggest that early
      activation of lipoxygenase is a key element in the execution of apoptosis induced
      by oxidative stress in plant cells, in a way surprisingly similar to that
      observed in animal cells.

PMID- 10931191
TI  - Highly potent inhibitors of human cathepsin L identified by screening
      combinatorial pentapeptide amide collections.
AB  - By screening a combinatorial pentapeptide amide collection in an inhibition
      assay, we systematically evaluated the potential of 19 proteinogenic amino acids
      and seven nonproteinogenic amino acids to serve as building blocks for inhibitors
      of human cathepsin L. Particularly efficient were aromatic, bulky, hydrophobic
      amino-acid residues, especially leucine, and positively charged residues,
      especially arginine. Building blocks for potential inhibitory peptides were
      combined by random selection from their activity pattern. This random approach
      for the design of inhibitors was introduced to compensate for the inaccuracy
      induced by shifted docking of combinatorial compound collections at the active
      center of cathepsin L. Thereby, we obtained structurally defined pentapeptide
      amides which inhibited human cathepsin L at nanomolar concentrations. Among the
      most potent novel inhibitors, one peptide, RKLLW-NH2, shares the amphiphilic
      character of the nonamer fragment VMNGLQNRK of the autoinhibitory, substrate
      like, but reverse-binding prosegment of human cathepsin L which blocks the active
      center of the enzyme. Obviously, RKLLW-NH2 carries the functions that are
      important for enzyme-peptide interaction in a condensed form. This hypothesis was
      confirmed by structure-activity studies using truncated and modified
      pentapeptides.

PMID- 10931192
TI  - Roles of cysteines in rat dipeptidyl peptidase IV/CD26 in processing and
      proteolytic activity.
AB  - The multifunctional type II transmembrane glycoprotein, dipeptidyl peptidase IV
      (DPPIV, EC 3.4.14.5), is expressed by almost all mammalian cells and is identical
      to the adenosine deaminase binding protein CD26 on lymphocytes. The extracellular
      part of rat DPPIV can be divided into three domains the middle part of which
      harbors 10 of the 12 highly conserved cysteine residues. The cysteine-rich domain
      is responsible for DPPIV-binding to collagen I and to extracellular ADA. The
      participation of distinct cysteines in disulfide bridges is not yet known.
      Titration experiments have shown the presence of six free cysteines and three
      disulfide bridges in native rat DPPIV. To investigate the role of distinct
      cysteines in the structure-function relationships of rat DPPIV we constructed 12
      different cysteine point mutations (C299, C326, C383, C455, C650 mutated to G;
      C337, C395, C445, C448, C473, C552, C763 mutated to S). Intracellular
      translocation to the cell surface of stable transfected Chinese hamster ovary
      cells was examined with antibodies against different epitopes of DPPIV. Surface
      expression of mutants C326G, C445S and C448S is inhibited totally; mutants C337S,
      C455G, C473S and C552S show weak expression only. In parallel, the half-life of
      these mutants is reduced to < 10% compared with wild-type enzyme. We were able to
      show that the specific peptidase activity of the mutant protein depends on cell
      surface expression, dimerization and the existence of a 150-kDa form demonstrable
      by nondenaturing SDS/PAGE. We conclude that cysteine residues 326, 337, 445, 448,
      455, 473 and 552 in rat DPPIV are essential for the correct folding and
      intracellular trafficking of this glycoprotein, and therefore for its normal
      biological properties.

PMID- 10931193
TI  - Synthetic substrates and inhibitors of beta-poly(L-malate)-hydrolase
      (polymalatase).
AB  - Polymalatase from Physarum polycephalum calalysed the hydrolysis of beta-poly[L
      malate] and of the synthetic compounds beta-di(L-malate), beta-tetra(L-malate),
      beta-tetra(L-malate) beta-propylester, and L-malate beta-methylester. Cyclic beta
      tri(L-malate), cyclic beta-tetra(L-malate), and D-malate beta-methylester were
      not cleaved, but were competitive inhibitors. The O-terminal acetate of beta
      tetra(L-malate) was neither a substrate nor an inhibitor. L-Malate was liberated;
      the Km, Ki and Vmax values were measured. The appearance of comparable amounts of
      beta-tri(L-malate), and beta-di(L-malate) during the cleavage of beta-tetra(L
      malate) indicated a distributive mechanism for small substrates. The accumulation
      of a series of oligomers, peaking with the 11-mer and 12-mer in the absence of
      higher intermediates, indicated that the depolymerization of beta-poly(L-malate)
      was processive. The results indicate that beta-poly(L-malate) is anchored at its
      OH-terminus by the highly specific binding of the penultimate malyl residue. The
      malyl moieties beyond 12 residues downstream from the OH-terminus extend into a
      diffuse second, electrostatic binding site. The catalytic site joins the first
      binding site, accounting for the cleavage of the polymer into malate residues. It
      is proposed that the enzyme does not dissociate from beta-poly(L-malate) during
      hydrolysis, when both sites are filled with the polymer. When only the first
      binding site is filled, the reaction partitions at each oligomer between
      hydrolysis and dissociation.

PMID- 10931195
TI  - The plant aspartic proteinase-specific polypeptide insert is not directly related
      to the activity of oryzasin 1.
AB  - Many plant aspartic proteinases (APs) are different from animal and microbial APs
      in that they contain a polypeptide insert, approximately 100 amino acids in
      length, in the C-terminal region. To interpret the significance of this insert,
      we constructed an expression system for rice AP oryzasin 1 by linking a pro
      oryzasin 1 downstream of glutathione S-transferase (GST). GST-proOS1 expressed
      the highest degree of hemoglobin-hydrolytic activity when treated at pH 3.3 and
      incubated for 24 h at room temperature. We carried out a similar experiment using
      an insert-lacking proOS1 mutant, GST-DeltaproOS1, as the fusion protein, and
      found it to show similar activity. This result indicates that the insert is not
      involved in the production of AP activity. We then investigated the autolysis of
      the two proteins by Western blot analysis. GST-proOS1 was autolyzed into 67- and
      64-kDa fragments, while GST-DeltaproOS1 autolyzed to 54- and 52-kDa products. GST
      DeltaproOS1 clearly produced two molecular species early in the autolytic
      process, and not later than 3 h from the start, but no such clear result was
      observed in the case of GST-proOS1. This suggests that, although the presence of
      the plant AP-specific insert does not influence the enzyme activity by itself, it
      apparently has an effect on the autolysis of OS1.

PMID- 10931194
TI  - Dynamics of biosynthesis and release of crustacean hyperglycemic hormone isoforms
      in the X-organ-sinus gland complex of the crayfish Orconectes limosus.
AB  - The crustacean hyperglycemic hormone (CHH) is the major neuropeptide produced by
      the X-organ-sinus gland neurosecretory system of the crayfish, Orconectes
      limosus. This hormone is synthesized by two different cell types, as two isomers
      (CHH and D-Phe3-CHH) which display different activities The aim of this report is
      to analyze and compare the synthetic and secretory activities of these
      specialized cells. In vitro pulse-chase incubations and time-course experiments
      were conducted on isolated X-organ-sinus gland (XO-SG) complexes, followed by
      analysis of the labeled peptides. The different steps of the post-translational
      processing of the CHH precursor, including proteolytic cleavage of the
      propeptide, C-terminal amidation and N-terminal pyroglutamylation were
      characterized and the kinetics of CHHs maturation were estimated in the different
      parts of the neuroendocrine complex. Furthermore, synthesis of CHHs in XO-SG
      complexes and release in incubation media were investigated using combined
      HPLC/immunoassay. Under basal conditions, i.e. without stimulation, similar
      dynamics for both isomers were found and results indicate that newly synthesized
      CHHs are preferentially released.

PMID- 10931196
TI  - Purification and characterization of the single-strand-specific and guanylic-acid
      preferential deoxyribonuclease activity of the extracellular nuclease from
      Basidiobolus haptosporus.
AB  - An extracellular nuclease from Basidiobolus haptosporus (designated as nuclease
      Bh1) was purified to homogeneity by ammonium sulfate precipitation, heat
      treatment, negative adsorption on DEAE-cellulose, and chromatography on phenyl
      Sepharose followed by FPLC on phenyl-Superose. The overall yield was 26%. The Mr
      of the purified enzyme, determined by gel filtration, was 41 000 whereas by
      SDS/PAGE (after deglycosylation) it was 30 000. It is a glycoprotein with a pI of
      6.8. The optimum pH and temperature for DNA hydrolysis were 8. 5 and 60 degrees
      C, respectively. Nuclease Bh1 is a metalloprotein but has no obligate requirement
      for metal ions to be active, nor is its activity stimulated in the presence of
      metal ions. The enzyme was inhibited by Zn2+, Ag2+, Hg2+, Fe3+ and Al3+,
      inorganic phosphate, pyrophosphate, dithiothreitol, 2-mercaptoethanol, NaCl and
      KCl. It was stable to high concentrations of organic solvents and urea but
      susceptible to low concentrations of SDS and guanidine hydrochloride. Nuclease
      Bh1 is a multifunctional enzyme and its substrate specificity is in the order of
      ssDNA approximately 3'AMP >> RNA > dsDNA. Studies on its mode of action showed
      that it cleaved supercoiled pUC 18 DNA and phage M13 DNA, endonucleolytically,
      generating single base nicks. The enzyme hydrolyzed DNA with preferential
      liberation of 5'dGMP, suggesting it to be a guanylic acid preferential
      endoexonuclease. 5'dGMP, the end product of hydrolysis, was a competitive
      inhibitor of the enzyme. The absence of 5'dCMP as a hydrolytic product, coupled
      with the resistance of (dC)10 and deoxyribodinucleoside monophosphates having
      cytosine either at the 3' or the 5' end, indicates that C-linkages are resistant
      to cleavage by nuclease Bh1.

PMID- 10931197
TI  - 31P-NMR and 13C-NMR studies of mannose metabolism in Plesiomonas shigelloides.
      Toxic effect of mannose on growth.
AB  - The metabolism of mannose was examined in resting cells in vivo using 13C-NMR and
      31P-NMR spectroscopy, in cell-free extracts in vitro using 31P-NMR spectroscopy,
      and by enzyme assays. Plesiomonas shigelloides was shown to transport mannose by
      a phosphoenolpyruvate-dependent phosphotransferase system producing mannose 6
      phosphate. However, a toxic effect was observed when P. shigelloides was grown in
      the presence of mannose. Investigation of mannose metabolism using in vivo 13C
      NMR showed mannose 6-phosphate accumulation without further metabolism. In
      contrast, glucose was quickly metabolized under the same conditions to lactate,
      ethanol, acetate and succinate. Extracts of P. shigelloides exhibited no mannose
      6-phosphate isomerase activity whereas the key enzyme of the Embden-Meyerhof
      pathway (6-phosphofructokinase) was found. This result explains the mannose 6
      phosphate accumulation observed in cells grown on mannose. The levels of
      phosphoenolpyruvate and Pi were estimated by in vivo 31P-NMR spectroscopy. The
      intracellular concentrations of phosphoenolpyruvate and Pi were relatively
      constant in both starved cells and mannose-metabolizing cells. In glucose
      metabolizing cells, the phosphoenolpyruvate concentration was lower, and about
      80% of the Pi was used during the first 10 min. It thus appears that the toxic
      effect of mannose on growth is not due to energy depletion but probably to a
      toxic effect of mannose 6-phosphate.

PMID- 10931198
TI  - Quantitative analysis of Na+-Ca2+ exchanger expression in guinea-pig heart.
AB  - In previous studies, regional variations in the expression of the Na+-Ca2+
      exchanger (NCX) have been examined qualitatively in human heart using the C2C12
      monoclonal antibody [Wang, J., Schwinger, R.H., Frank, K., Muller-Ehmsen, J.,
      Martin-Vasallo, P., Pressley, T.A., Xiang, A., Erdmann, E. & McDonough, A.A.
      (1996) J. Clin. Invest. 98, 1650-1658]. Although NCX expression was found to be
      significantly lower in the atria compared to the septum, no significant
      differences were found between atrial and ventricular tissue. NCX has been
      located in the general sarcolemma and t-tubules of ventricular muscle and as t
      tubules are sparse in atrial tissue compared to ventricular tissue, it is
      surprising that NCX expression was found to be similar in both atria and
      ventricles [Wang et al. (1996)]. To reinvestigate this, we have used SDS/PAGE and
      a quantitative Western blotting technique to determine the pattern of expression
      of NCX in guinea-pig heart in tissue samples from left atrium, right atrium,
      septum, left ventricle and right ventricle. NCX protein expression was 17.5 +/-
      3.9 pmol.mg-1 of protein in the left atrium and 29.2 +/- 6.1 pmol.mg-1 of protein
      in the right atrium, which were both significantly lower (P < 0.05) than NCX
      expression in the septum, left ventricle and right ventricle (64.7 +/- 15.2, 76.8
      +/- 19.5 and 69.4 +/- 14.1 pmol.mg-1 of protein, respectively, n = 7). These
      differences in NCX expression may reflect variations in the cellular location of
      NCX protein in these regions. To study this, we used confocal immunofluorescence
      of single isolated myocytes to examine differences in the proportion of
      fluorescent staining on the general surface membrane compared with the interior
      of the cell (which presumably reflects a t-tubular location). We found that the
      general membrane staining was 79.0 +/- 1.2% in cells from the atria which was
      significantly higher (P < 0. 001) than that seen in cells from the septum, left
      ventricle and right ventricle, with 48.1 +/- 1.1%, 48.2 +/- 1.8% and 45.6 +/-
      1.3%, respectively (n = 20). These results illustrate a similar pattern of NCX
      expression in guinea-pig and human, with expression in atrial tissue
      significantly lower than in ventricular tissue. However, the cellular location of
      NCX differs regionally; in atrial tissue, the majority of the NCX protein is
      located in the general sarcolemma whereas in ventricular and septal tissue,
      approximately 50% of NCX protein is located within the cell (presumably at the
      level of the t-tubules).

PMID- 10931199
TI  - Chemical synthesis and characterization of Pi1, a scorpion toxin from Pandinus
      imperator active on K+ channels.
AB  - Pi1 is a 35-residue toxin cross-linked by four disulfide bridges that has been
      isolated from the venom of the chactidae scorpion Pandinus imperator. Due to its
      very low abundance in the venom, we have chemically synthesized this toxin in
      order to study its biological activity. Enzyme-based proteolytic cleavage of the
      synthetic Pi1 (sPi1) demonstrates half-cystine pairings between Cys4-Cys25, Cys10
      Cys30, Cys14-Cys32 and Cys20-Cys35, which is in agreement with the disulfide
      bridge organization initially reported on the natural toxin. In vivo,
      intracerebroventricular injection of sPi1 in mice produces lethal effects with an
      LD50 of 0.2 microgram per mouse. In vitro, the application of sPi1 induces
      drastic inhibition of Shaker B (IC50 of 23 nM) and rat Kv1.2 channels (IC50 of
      0.44 nM) heterologously expressed in Xenopus laevis oocytes. No effect was
      observed on rat Kv1.1 and Kv1.3 currents upon synthetic peptide application.
      Also, sPi1 is able to compete with 125I-labeled apamin for binding onto rat brain
      synaptosomes with an IC50 of 55 pM. Overall, these results demonstrate that sPi1
      displays a large spectrum of activities by blocking both SK- and Kv1-types of K+
      channels; a selectivity reminiscent of that of maurotoxin, another structurally
      related four disulfide-bridged scorpion toxin that exhibits a different half
      cystine pairing pattern.

PMID- 10931200
TI  - Flavin-protein interactions in flavocytochrome b2 as studied by NMR after
      reconstitution of the enzyme with 13C- and 15N-labelled flavin.
AB  - A new procedure was devised for reversibly removing the flavin from
      flavocytochrome b2. It allowed reconstitution with selectively enriched 13C- and
      15N-labelled FMN for an NMR analysis of the chemical shifts of the enriched
      positions as well as that of 31P. From these measurements, it was possible to
      deduce information about the hydrogen-bonding pattern of FMN in the protein, the
      hybridization states of the nitrogen atoms and (in part) the pi-electron
      distribution. The carbonyl groups at C(2) and C(4) and the nitrogen atoms N(1)
      and N(5) form hydrogen bonds to the apoenzyme in both redox states. Nevertheless,
      according to 15N-chemical shifts, the bond from the protein to N(3) is very weak
      in both redox states, whereas that to N(5) is strong for the oxidized state, and
      is weakened upon flavin reduction. On the other hand, the 13C-NMR results
      indicate that the C(2) and C(4) carbonyl oxygens form stronger hydrogen bonds
      with the enzyme than most other flavoproteins in both redox states. From coupling
      constant measurements it is shown that the N(3) proton is not solvent accessible.
      Although no N-H coupling constant could be measured for N(5) in the reduced state
      due to lack of resolution, N(5) is clearly protonated in flavocytochrome b2 as in
      all other known flavoproteins. With respect to N(10), it is more sp3-hybridized
      in the oxidized state than in free FMN, whereas the other nitrogen atoms show a
      nearly planar structure. In the reduced state, N(5) and N(10) in bound FMN are
      both more sp3-hybridized than in free FMN, but N(5) exhibits a higher degree of
      sp3-hybridization than N(10), which is only slightly shifted out of the
      isoalloxazine plane. In addition, two-electron reduction of the enzyme leads to
      anion formation on N(1), as indicated by its 15N-chemical shift of N(1) and
      characteristic upfield shifts of the resonances of C(2), C(4) and C(4a) compared
      to the oxidized state, as observed for most flavoproteins. 31P-NMR measurements
      show that the phosphate geometry has changed in enzyme bound FMN compared to the
      free flavin in water, indicating a strong interaction of the phosphate group with
      the apoenzyme.

PMID- 10931201
TI  - PAP-1, a novel target protein of phosphorylation by pim-1 kinase.
AB  - Protooncogene, pim-1, has been reported to be a predisposition for
      lymphomagenesis along with myc, and its protein product, Pim-1, has been shown to
      be a serine/threonine protein kinase, whose activity is involved in proliferation
      and differentiation of blood cells. The signal transduction pathways neither to
      nor from Pim-1, however, have been clarified. We have cloned a cDNA encoding a
      novel Pim-1 binding protein, PAP-1, comprising 213 amino acids with a basic amino
      acid cluster near the C-terminus. PAP-1 was colocalized with Pim-1 in human HeLa
      cell nuclei. The in vitro binding assays using GST fusion proteins of the wild
      type and various deletion mutants revealed that the whole molecule of Pim-1 is
      required for the binding activity to PAP-1 and that Pim-1 binds to the region
      from amino-acid numbers 1-147 of PAP-1, or to two segments in the region. The
      association of PAP-1 with Pim-1 was also shown in vivo in transfected cells.
      Furthermore, PAP-1 was phosphorylated in vitro by Pim-1, but not a kinase
      negative Pim-1 mutant. The two serine residues of PAP-1 at amino acids 204 and
      206 near the C-terminus were phosphorylated by Pim-1. PAP-1 is thus thought to be
      a target protein for Pim-1 kinase.

PMID- 10931202
TI  - 18O-Labelling pattern of okadaic acid from H218O in dinoflagellate Prorocentrum
      lima elucidated by tandem mass spectrometry.
AB  - Okadaic acid is a metabolite of the unicellular algae dinoflagellate. Its
      biosynthesis has attracted considerable attention since the skeletal structure
      was shown to be synthesized via an unprecedented route. However, its relevant
      intermediates or enzymes are unknown. In the course of our previous
      investigations on the oxygen source of okadaic acid by tandem mass spectrometry
      (CID MS/MS), we determined the level of 18O incorporation for each oxygen site
      from 18O2 and [18O2]acetate. In the present study, we examined H218O-labelling
      patterns of okadaic acid from dinoflagellates in comparison with salinomycin from
      actinomycetes and has provided intriguing information regarding biosynthesis.
      Unexpectedly, oxygen atoms originating from acetate were not labelled from H218O;
      this can not be accounted for by the usual metabolic route where acetyl-CoA is
      biosynthesized via pyruvate. Similar experiments for salinomycin revealed that
      all of its oxygen atoms derived from acetate or propionate were labelled by
      H218O. Another interesting feature is that two oxygen sites were derived from
      both O2 and H2O while the others were labelled only from O2. These results imply
      that an oxidation mechanism other than those in actinomycetes polyethers may be
      involved in the biosynthesis of okadaic acid.

PMID- 10931203
TI  - The crystal structure of the complex of Zea mays alpha subunit with a fragment of
      human beta subunit provides the clue to the architecture of protein kinase CK2
      holoenzyme.
AB  - The crystal structure of a complex between the catalytic alpha subunit of Zea
      mays CK2 and a 23-mer peptide corresponding the C-terminal sequence 181-203 of
      the human CK2 regulatory beta subunit has been determined at 3.16-A resolution.
      The complex, composed of two alpha chains and two peptides, presents a molecular
      twofold axis, with each peptide interacting with both alpha chains. In the
      derived model of the holoenzyme, the regulatory subunits are positioned on the
      opposite side with respect to the opening of the catalytic sites, that remain
      accessible to substrates and cosubstrates. The beta subunit can influence the
      catalytic activity both directly and by promoting the formation of the alpha2
      dimer, in which each alpha chain interacts with the active site of the other.
      Furthermore, the two active sites are so close in space that they can
      simultaneously bind and phosphorylate two phosphoacceptor residues of the same
      substrate.

PMID- 10931204
TI  - Identification of residues critical for toxicity in Clostridium perfringens
      phospholipase C, the key toxin in gas gangrene.
AB  - Clostridium perfringens phospholipase C (PLC), also called alpha-toxin, is the
      major virulence factor in the pathogenesis of gas gangrene. The toxic activities
      of genetically engineered alpha-toxin variants harboring single amino-acid
      substitutions in three loops of its C-terminal domain were studied. The
      substitutions were made in aspartic acid residues which bind calcium, and
      tyrosine residues of the putative membrane-interacting region. The variants D269N
      and D336N had less than 20% of the hemolytic activity and displayed a cytotoxic
      potency 103-fold lower than that of the wild-type toxin. The variants in which
      Tyr275, Tyr307, and Tyr331 were substituted by Asn, Phe, or Leu had 11-73% of the
      hemolytic activity and exhibited a cytotoxic potency 102- to 105-fold lower than
      that of the wild-type toxin. The results demonstrated that the sphingomyelinase
      activity and the C-terminal domain are required for myotoxicity in vivo and that
      the variants D269N, D336N, Y275N, Y307F, and Y331L had less than 12% of the
      myotoxic activity displayed by the wild-type toxin. This work therefore
      identifies residues critical for the toxic activities of C. perfringens PLC and
      provides new insights toward understanding the mechanism of action of this toxin
      at a molecular level.

PMID- 10931205
TI  - Novel polysialogangliosides of skate brain structural determination of tetra,
      penta and hexasialogangliosides with a NeuAc-GalNAc linkage.
AB  - The gangliosides in the brain of a cartilaginous fish, skate (Bathyraja
      smirnovi), have been isolated and characterized by means of methylation analysis,
      antibody binding, enzymatic hydrolysis and MALDI-TOF MS. In addition to
      gangliosides with known structures (GM2, fucosyl-GM1, GD3, GD2, GT3 and GT2),
      five polysialogangliosides were isolated and characterized as having the
      following structures. (1) IV3NeuAc, III6NeuAc, II3NeuAc-Gg4Cer; (2) IV3NeuAc2,
      III6NeuAc, II3NeuAc-Gg4Cer; (3) IV3NeuAc, III6NeuAc, II3NeuAc2-Gg4Cer; (4)
      IV3NeuAc, III6NeuAc, II3NeuAc3-Gg4Cer; and (5) IV3NeuAc2, III6NeuAc, II3NeuAc3
      Gg4Cer. These structures are 'hybrid-type' which comprise combinations of alpha
      series and either a, b or c-series structures. Three gangliosides (2), (4) and
      (5), were novel. The main features of the ganglioside composition of skate brain
      were an abundance of gangliotriaosyl species, a lack of gangliotetraosyl species
      (except fucosyl-GM1), and an abundance of hybrid-types. These characteristics
      closely resemble those in shark brain which we reported previously [Nakamura, K.,
      Tamai, Y. & Kasama, T. (1997) Neurochem. Int. 30, 593-604]. Two of the hybrid
      type gangliosides (1) and (4), were examined for their neuritogenic activity
      toward cultured neuronal cells (Neuro-2A), and were found to have more potent
      activity than nonhybrid-type gangliosides such as GM1.

PMID- 10931206
TI  - Biochemical characterization of recombinant subunits of type 2A protein
      phosphatase overexpressed in Pichia pastoris.
AB  - Methylotrophic yeast Pichia pastoris was used for a medium-scale expression of
      structural (PR65/A) and catalytic (PP2Ac) subunits of human type 2A protein
      phosphatase (PP2A). Constructs encoding these subunits, which were designed to
      introduce eight histidines at their N-termini, were introduced into the KM71
      Pichia strain by homologous recombination. Recombinant proteins overproduced
      after methanol induction were purified from cell-free extracts by anion-exchange
      chromatography on DEAE-Sepharose, and Ni2+/nitrilotriacetate/agarose. In
      addition, chromatography on omega-aminohexyl-Sepharose was applied to purify
      recombinant (r)PR65/A. This purification scheme yielded approximately 5 mg and
      100 microg of rPR65/A and rPP2Ac, respectively, from 1 L of the yeast culture.
      The specific activity of rPP2Ac measured with [32P]phosphorylase a [1.7
      micromol.min-1.(mg protein)-1] and its inhibition by okadaic acid (IC50 = 0.66
      nM) were similar to PP2A isolated from rabbit skeletal muscle. As demonstrated by
      immunodetection with methylation state-specific antibodies, recombinant PP2Ac was
      carboxymethylated at the last C-terminal leucine residue. Recombinant PP2A
      subunits were able to form a complex as demonstrated both by activity assays in
      the presence of protamine and by chromatography on protamine-agarose. In summary,
      P. pastoris provides a convenient heterologous system for the production of
      recombinant subunits of PP2A.

PMID- 10931207
TI  - Characterization and kinetic mechanism of mono- and bifunctional ornithine
      acetyltransferases from thermophilic microorganisms.
AB  - The argJ gene coding for N2-acetyl-L-ornithine: L-glutamate N-acetyltransferase,
      the key enzyme involved in the acetyl cycle of L-arginine biosynthesis, has been
      cloned from thermophilic procaryotes: the archaeon Methanoccocus jannaschii, and
      the bacteria Thermotoga neapolitana and Bacillus stearothermophilus. Archaeal
      argJ only complements an Escherichia coli argE mutant (deficient in
      acetylornithinase, which catalyzes the fifth step in the linear biosynthetic
      pathway), whereas bacterial genes additionally complement an argA mutant
      (deficient in N-acetylglutamate synthetase, the first enzyme of the pathway). In
      keeping with these in vivo data the purified His-tagged ArgJ enzyme of M.
      jannaschii only catalyzes N2-acetylornithine conversion to ornithine, whereas T.
      neapolitana and B. stearothermophilus ArgJ also catalyze the conversion of
      glutamate to N-acetylglutamate using acetylCoA as the acetyl donor. M. jannaschii
      ArgJ is therefore a monofunctional enzyme, whereas T. neapolitana and B.
      stearothermophilus encoded ArgJ are bifunctional. Kinetic data demonstrate that
      in all three thermophilic organisms ArgJ-mediated catalysis follows ping-pong bi
      bi kinetic mechanism. Acetylated ArgJ intermediates were detected in
      semireactions using [14C]acetylCoA or [14C]N2-acetyl-L-glutamate as acetyl
      donors. In this catalysis L-ornithine acts as an inhibitor; this amino acid
      therefore appears to be a key regulatory molecule in the acetyl cycle of L
      arginine synthesis. Thermophilic ArgJ are synthesized as protein precursors
      undergoing internal cleavage to generate alpha and beta subunits which appear to
      assemble to alpha2beta2 heterotetramers in E. coli. The cleavage occurs between
      alanine and threonine residues within the highly conserved PXM-ATML motif
      detected in all available ArgJ sequences.

PMID- 10931208
TI  - Polypeptide chain composition diversity of hexagonal-bilayer haemoglobins within
      a single family of annelids, the alvinellidae.
AB  - Following previous analysis of the structure of Alvinella pompejana heaxagonal
      bilayer haemoglobin (HBL Hb) [1], we report in this paper the structure of three
      other HBL Hbs belonging to Alvinella caudata, Paralvinella grasslei and
      Paralvinella palmiformis, members of the Alvinellidae, annelid family strictly
      endemic to deep-sea hydrothermal vents located on the ridge crests in the Pacific
      ocean. The multi-angle laser light scattering (MALLS) and fast protein liquid
      chromatography (FPLC) analysis revealed a broad range of molecular masses for the
      extracellular Hb molecules, 3517 +/- 14 kDa (A. caudata), 3822 +/- 28 kDa (P.
      grasslei) and 3750 +/- 150 kDa (P. palmiformis). Native and derivative Hbs
      (reduced, carbamidomethylated and deglycosylated) were analysed by electrospray
      ionization mass spectroscopy (ESI-MS) and the data was processed by the maximum
      entropy deconvolution system (MaxEnt). The most important difference between
      alvinellid HBL Hbs was the variation in their composition, from two to four
      monomeric globin chains, and from one to four linker chains. Therefore, despite
      the fact that all these species belong to a single family, notable differences in
      the polypeptide chain composition of their HBL Hbs were observed, probably
      accounting for their different functional properties as previously reported by
      this group Toulmond, A., El Idrissi Slitine, F., De Frescheville, J. & Jouin, C.
      (1990) Biol. Bull. 179, 366-373.

PMID- 10931209
TI  - Control of cellular phosphatidylinositol 4,5-bisphosphate levels by adhesion
      signals and rho GTPases in NIH 3T3 fibroblasts involvement of both
      phosphatidylinositol-4-phosphate 5-kinase and phospholipase C.
AB  - The involvement of small GTPases of the Rho family in the control of
      phosphoinositide metabolism by adhesion signals was examined in NIH 3T3
      fibroblasts. Abrogation of adhesion signals by detachment of cells from their
      substratum resulted in a time-dependent decrease in the cellular level of
      PtdIns(4,5)P2 by approximately 50%. This effect could be mimicked by treatment of
      adherent cells with Clostridium difficile toxin B and toxin B-1470, which inhibit
      specific subsets of Rho and Ras GTPases. Detachment of cells that had been
      pretreated with the clostridial toxins did not cause a further reduction in
      PtdIns(4,5)P2 levels, suggesting that the target GTPases are integrated into the
      control of phosphoinositide levels by adhesion signals. The reduction in
      PtdIns(4,5)P2 levels could be attributed to reduced activity of the major
      PtdIns(4, 5)P2-producing enzyme, PtdIns4P 5-kinase. Unexpectedly, both cell
      detachment and toxin treatment resulted in a twofold to threefold increase in
      inositol phosphate production in intact cells. In lysates of these cells, in
      vitro phospholipase C activity was found to be elevated by 30-50%. The effects of
      cell detachment and toxin treatment on inositol phosphate formation could be
      mimicked by expression of dominant-negative N17 Rac1. Taken together, these data
      suggest that adhesion-controlled small GTPases of the Rho family are involved in
      the regulation of the cellular PtdIns(4,5)P2 levels in NIH 3T3 fibroblasts, by
      controlling the activities of both PtdIns4P 5-kinase and phospholipase C.

PMID- 10931210
TI  - Functional characterization of green fluorescent protein-profilin fusion
      proteins.
AB  - To clarify the role of profilins in cells, fusion proteins constructed with green
      fluorescent protein (GFP) should be extremely helpful. As profilins are
      considerably smaller than the GFP fusion partner (14-17 kDa compared with 27 kDa,
      respectively), we characterized the fusion proteins in vitro, to ascertain their
      biological function. We fused mouse profilin I and II to either the C-terminus or
      N-terminus of GFP. These fusion proteins were expressed in Escherichia coli and
      affinity-purified on polyproline-Sepharose. Interaction with vasodilator
      stimulated phosphoprotein, a proline-rich ligand of profilin, was investigated by
      ELISA, as was binding to PtdIns(4,5)P2. The affinity for actin was quantitatively
      determined in polymerization assays. Our results show that fusion of GFP to the C
      terminus of profilin I abolishes polyproline binding. In contrast, the other
      fusion proteins bound to polyproline-Sepharose and VASP. Binding to PtdIns(4,5)P2
      was not significantly altered. Furthermore, fusion of either isoform with GFP did
      not decrease the affinity for actin. In localization studies with mammalian
      cells, all fusion proteins showed the localization expected for profilin in areas
      of high actin dynamics, such as leading lamellae and ruffles induced by epidermal
      growth factor. However, with regard to our in vitro data, we suspect that only a
      minor fraction of profilin I carrying the GFP at the C-terminus can target these
      sites. Therefore, other constructs should be preferred for further in vivo
      studies.

PMID- 10931211
TI  - The amino-acid sequence of the abalone (Haliotis laevigata) nacre protein
      perlucin. Detection of a functional C-type lectin domain with galactose/mannose
      specificity.
AB  - Perlucin isolated from abalone nacre consists of 155 amino acids including a
      glycosylated asparagine. The sequence of the first 130 amino acids shows a high
      similarity to the C-type carbohydrate-recognition domains of asialoglycoprotein
      receptors and other members of the group of C-type lectins but also a weaker
      similarity to related proteins without carbohydrate-binding activity. This C-type
      module is followed by a short C-terminal domain containing two almost identical
      sequence repeats with a length of 10 amino acids. Solid phase assays show a
      divalent metal ion-dependent binding of perlucin to (neo)glycoproteins containing
      D-galactose or D-mannose/D-glucose indicating that perlucin is a functional C
      type lectin with broad carbohydrate-binding specificity. Our results also
      indicate that it may be difficult to predict carbohydrate-binding specificity and
      the occurrence of alternative binding configurations by amino-acid sequence
      comparisons and homology modeling.

PMID- 10931212
TI  - Laboratory diagnosis of variant Creutzfeldt-Jakob disease.
AB  - The neuropathological and biochemical features of 33 cases of variant Creutzfeldt
      Jakob disease (vCJD) diagnosed up to the end of 1998 are analysed in relation to
      the 646 cases of suspected CJD referred to the CJD Surveillance Unit laboratory
      from 1990 to 1998. Morphological studies of the central nervous system, lymphoid
      tissues and other organs were accompanied by immunocytochemistry; Western blot
      analysis of PrPRES was performed on frozen brain tissue. The findings were
      analysed in relation to clinical and genetic data. The pathology of vCJD showed
      morphological and immunocytochemical characteristics distinct from other cases of
      CJD. PrP accumulation was widespread in lymphoid tissues in vCJD, but was not
      identified in other non-neural tissues. PrPRES accumulation in vCJD brain tissue
      showed a uniform glycotype pattern distinct from sporadic CJD. All analysed cases
      of vCJD were methionine homozygotes at codon 129 of the PrP gene. No evidence
      currently exists to suggest that cases of CJD diagnosed in individuals who are MV
      or VV at codon 129 of the PrP gene represent 'human bovine spongiform
      encaphalopathy (BSE)'. Continued surveillance is required to further investigate
      this possibility, with the need to investigate autopsy tissues from suspected
      cases by histological and biochemical techniques.

PMID- 10931213
TI  - A reassessment of primary thyroid lymphoma: high-grade MALT-type lymphoma as a
      distinct subtype of diffuse large B-cell lymphoma.
AB  - AIMS: Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease.
      During an 18-year period, 53 cases of primary non-Hodgkin's lymphoma involving
      this extranodal site were seen at our institutions. The aims of this study were
      to evaluate the spectrum of PTLs using current lymphoma classification concepts
      and immunocytochemical markers, determine whether features of MALT-type lymphoma
      were evident in PTL, and if there was any clinical significance of such a
      finding. METHODS AND RESULTS: The cases were retrospectively studied clinically,
      histologically and immunohistochemically. The tumours were classified according
      to the Revised European-American Lymphoma Classification of lymphoid malignancies
      (REAL classification). Thirty-eight patients were females, 15 were males and mean
      age at diagnosis was 66.3 years (range 38-90). Three cases were low-grade
      marginal zone lymphomas (low-grade MALT-type lymphomas). There were 45 diffuse
      large B-cell lymphomas (DLBCL) of which there were 27 DLBCL-NOS and 18 high-grade
      MALT-type lymphomas. Within the diffuse large B-cell lymphoma (DLBCL) category,
      cases were subdivided into those without (DLBCL-NOS) and those with features of
      'high-grade' MALT-type lymphoma based on presence of a low-grade component or
      large cell lymphoepithelial lesions (HG MALT-type lymphoma). In addition there
      were three follicle centre lymphomas, one anaplastic large cell lymphoma and one
      peripheral T-cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four
      stage IV. All patients with low-grade MALT-type lymphoma are alive without
      disease. The 5-year survivals for DLBCL-NOS and HG MALT-type lymphoma were 75%
      and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed
      stage (P < 0.001) and subtype (P = 0.005) were associated with survival. Stage
      was associated with type of DLBCL, 65% of DLBCL-NOS being stage IE compared to
      20% of HG MALT-type lymphomas. CONCLUSIONS: We conclude that primary thyroid
      lymphomas occur most commonly in elderly women and are frequently present in
      clinical stage IE and IIE. Low-grade MALT-type lymphomas are relatively uncommon
      but appear to have a favourable prognosis. DLBCL is the most common lymphoma and
      features of MALT can be seen in over one-third of cases. As a group, HG MALT-type
      lymphomas had a worse outcome than DLBCL-NOS, primarily due to higher clinical
      stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical
      and histological entities.

PMID- 10931214
TI  - Frequent presence of neuroendocrine small cells in thymic carcinoma: a light
      microscopic and immunohistochemical study.
AB  - AIMS: Neuroendocrine differentiation has been described in conventional
      carcinomas of various organs. Small cells postulated to be neuroendocrine cells
      were observed previously in some thymic carcinomas. This study was conducted to
      confirm and characterize the presence of neuroendocrine small cells in thymic
      carcinomas by light microscopy and immunohistochemistry. METHODS AND RESULTS:
      Twenty-two thymic carcinomas were studied by light microscopy to detect the
      presence of small neuroendocrine-like cells. They were found in four of 10
      squamous cell carcinomas (SCC) and seven of eight adenosquamous carcinomas (ASC).
      No small cells were observed in three lymphoepithelioma-like carcinomas (LELC)
      and one adenocarcinoma. The small cells were located within the tumour nests and
      constituted less than 1% of the entire tumour. In one case, small cells also
      extended outside the tumour nests. Rosette formation was seen in three cases.
      They were proved to be neuroendocrine cells by their immunoreactivity to neuron
      specific enolase, chromogranin A, and/or synaptophysin. A few scattered
      neuroendocrine small cells were found only by immunohistochemistry in one case
      each of SCC, ASC, and LELC. The small cells were also strongly positive for
      cytokeratin (CK) 8 and CK18 but negative for CK19 and CK20. The predominant
      carcinoma cells other than the neuroendocrine small cells also displayed
      neuroendocrine markers in 68% of the cases studied. CONCLUSIONS: Neuroendocrine
      small cells can be recognized by light microscopic examination in approximately
      61% of thymic SCC and ASC. Neuroendocrine markers, CK8 and CK18 can aid in
      confirming their presence. The neuroendocrine small cells present in thymic
      carcinomas are different from the main carcinoma cells displaying
      immunohistochemical neuroendocrine markers. The presence of neuroendocrine small
      cells could be an useful marker for the differentiation of thymic carcinomas from
      thymomas and carcinomas of other sites.

PMID- 10931215
TI  - Calretinin expression in ameloblastomas.
AB  - AIMS: Calretinin is a 29-kDa calcium-binding protein which is expressed in the
      central and peripheral nervous systems as well as in many other normal and
      pathological human tissues. The objective of this study was to determine whether
      calretinin was expressed in the epithelium of ameloblastomas. METHODS AND
      RESULTS: Twenty-seven cases of unicystic ameloblastoma and 31 cases of solid and
      multicystic ameloblastoma were studied. Five-micron sections were
      immunohistochemically stained using either antiserum 7696 from Swant, or
      antiserum 18-0211 from Zymed with a standard ABC method. The results were
      identical with the two antisera. Positive staining was seen in 22 cases (81.5%)
      of unicystic ameloblastomas. This generally consisted of diffuse, intense nuclear
      and cytoplasmic staining of several cell layers of the more superficial cells
      both in the characteristic and nondescript areas of the cyst linings. In the
      solid and multicystic ameloblastomas, staining occurred in 29 (93. 5%) of the
      cases. The staining was almost always restricted to the stellate reticulum-like
      epithelium, was generally intense and diffuse in distribution. Areas of squamous
      metaplasia stained particularly intensely as did the cells surrounding micro- and
      macro-cysts. In both groups of lesions, most of the cases that did not stain were
      intensely inflamed. CONCLUSIONS: The biological significance of calretinin
      expression in ameloblastomas is not known and its use as a distinctive, specific
      immunohistochemical marker for ameloblastic tissues remains to be confirmed.
      However, the results of this study raise the possibility that calretinin may be
      an important diagnostic aid in the differential diagnosis of cystic and solid
      ameloblastic tumours.

PMID- 10931216
TI  - 'Mucin-positive' epithelial mesothelioma of the peritoneum: an unusual diagnostic
      pitfall.
AB  - AIMS: The histopathological, immunohistochemical and ultrastructural features of
      a primary 'mucin-positive' epithelial mesothelioma of the peritoneum are reported
      to draw attention to a potential cause of diagnostic error. METHODS AND RESULTS:
      Light microscopy showed an infiltrative neoplasm within the gastric wall and
      omentum which was composed of sheets of 'signet- ring' tumour cells and contained
      abundant diastase-resistant periodic acid-Schiff-positive material.
      Immunohistochemistry supported a mesothelial phenotype (cytokeratin AE1/3, thick
      membranous HBME-1, focal thrombomodulin and calretinin expression and no
      reactivity for carcinoembryonic antigen, Leu-M1 and Ber-EP4). Ultrastructural
      features showed large cells with prominent intercellular desmosomes and numerous
      delicate, elongated microvilli. Within intracytoplasmic neolumina, crystalloidal
      'fern-like' bodies were identified with features similar to the ultrastructural
      appearances of hyaluronic acid crystals. Repeat histochemical analysis following
      hyaluronidase pretreatment revealed a significantly diminished diastase-resistant
      periodic acid-Schiff reaction. CONCLUSIONS: This case of primary peritoneal
      'mucin-positive' epithelial mesothelioma demonstrates morphological and
      histochemical mimicry with diffuse gastric adenocarcinoma. A similar case has not
      been previously reported in the peritoneum and an awareness of the tumour (with
      application of suitable ancillary studies) prevents misdiagnosis and assists in
      potentially difficult medicolegal cases.

PMID- 10931218
TI  - c-mos immunoreactivity is an indicator of good prognosis in lung cancer.
AB  - AIMS: Reports concerning the expression of cytoplasmic components of the mitogen
      activating protein kinase (MAPK) pathway in lung cancer are limited. One of the
      molecules participating in this pathway is the product of the c-mos proto
      oncogene. In vitro investigations, in somatic cells, have shown that c-mos
      expression has opposing effects on cell cycle progression suggesting that it may
      represent an important determinant of aberrant cell function. In this study we
      analysed, by immunohistochemical means, its status in a series of lung carcinomas
      and correlated the findings with clinicopathological parameters and survival of
      the patients. METHODS AND RESULTS: Sixty cases of lung carcinomas were included
      in the study. These comprised 52 non-small (NSCLCs) and eight small cell lung
      carcinomas (SCLCs). Sections from the carcinomas were immunostained with the
      polyclonal anti-c-mos antibody P-19. Specificity was tested by using the
      appropriate control peptide and control cell lines. Expression was observed in
      63% of the cases, with NSCLCs showing higher reactivity (67%) than SCLCs (37.5%).
      Staining was observed mainly to the cytoplasm and membranes of the cancerous
      cells, but some nuclei reacted as well. An intratumour heterogeneous
      immunoreactivity was noticed. The most interesting and unexpected finding was
      that c-mos positive staining was associated with better recurrence-free survival
      in our series, regardless of histological type (P = 0.035). Furthermore,
      favourable disease-related and recurrence-free survival was observed in the SqC
      group with c-mos immunoreactivity (P < 0. 001). CONCLUSIONS: c-mos proto-oncogene
      is expressed in a significant proportion of lung carcinomas and may play a role
      in its development. The fact that its expression is associated with a relatively
      good prognosis may be indicative of a negative impact on tumour growth.

PMID- 10931217
TI  - Rhabdoid tumour of the lung is a dedifferentiated phenotype of pulmonary
      adenocarcinoma.
AB  - AIMS: Primary rhabdoid tumour of the lung is rare, and histological and
      biological characteristics have not been fully documented. We describe three
      cases of primary lung rhabdoid tumour, all associated with adenocarcinoma, and
      investigate the histological features and biological characteristics. METHODS AND
      RESULTS: Three cases were obtained from a total 902 cases of surgically removed
      primary lung tumours between 1986 and 1998. The rhabdoid cells were found to
      occupy about 50-90% of each tumour. All of the tumours had nonrhabdoid
      adenocarcinoma foci in the centre of the tumours. Transition between the
      adenocarcinomatous and rhabdoid components was demonstrated. Detailed
      immunohistochemical studies were carried out. The epithelial markers,
      cytokeratins and epithelial membrane antigen (EMA), were strongly expressed in
      rhabdoid and adenocarcinomatous components. Furthermore, surfactant apoprotein A
      was positive in both components in one case, but myoglobin, MyoD and HHF35 were
      not expressed. Vimentin was strongly and diffusely stained in all cases. The
      neuroendocrine markers, chromogranin A (all cases), neuron-specific antigen (NSE)
      (two cases) and CD56 (one case) were occasionally positive in only a small number
      of the rhabdoid tumour cells. GM-CSF was positively stained in one case, and the
      dedifferentiated characteristics of the rhabdoid cells was suggested.
      Proliferative cell nuclear antigen (PCNA) was strongly demonstrated in the
      rhabdoid tumour cells (all cases). To gain better understanding the highly
      proliferative characteristics of the tumours, p53 gene (exons 5-8) mutation was
      examined by DNA sequencing analysis; mutation of the p53 DNA was not detected.
      Overexpression of p53 protein was also not demonstrated in all cases. HPV6 was
      demonstrated in one case by PCR method and also non-isotopic in-situ
      hybridization (NISH). Two cases died in a short period of time (3 years and 4
      months, respectively). CONCLUSION: The rhabdoid cells in these three cases were
      considered to represent the dedifferentiated components of the accompanying
      adenocarcinoma. Dedifferentiated characteristics (neuroendocrine markers, GM-CSF,
      vimentin, and the aggressive behaviour) were evident.

PMID- 10931219
TI  - Cytokeratin profile relates to histological subtypes and intrahepatic location of
      intrahepatic cholangiocarcinoma and primary sites of metastatic adenocarcinoma of
      liver.
AB  - AIMS: We evaluated the cytokeratin profile of intrahepatic cholangiocarcinoma
      with respect to its histological classification and intrahepatic location
      (peripheral vs. hilar), and compared its profile with that of a variety of
      metastatic adenocarcinomas in liver. METHODS AND RESULTS: Expression of
      cytokeratins 7, 8, 18, 19 and 20 was immunohistochemically examined in
      intrahepatic cholangiocarcinoma (n = 77) and metastatic adenocarcinoma in liver
      (21 colorectal, 14 gastric, three gallbladder and three pancreatic cancers).
      Materials were autopsy or surgical specimens. Cytokeratins 7, 8, 18 and 19 were
      expressed in 75 (97%), 75 (97%), 59 (77%) and 71 (92%) cases of intrahepatic
      cholangiocarcinoma, respectively. Moderate and extensive expression of
      cytokeratin 18 was more frequent in the peripheral than in the hilar type.
      Moderate and extensive expression of cytokeratin 19 was seen in almost all cases
      of well-differentiated intrahepatic cholangiocarcinomas, while expression was
      decreased relatively in the moderately and decreased more in the poorly
      differentiated cases. While cytokeratin 20 was not found in non-neoplastic
      biliary epithelia or in well-differentiated intrahepatic cholangiocarcinomas,
      this cytokeratin was occasionally detectable in moderately and poorly
      differentiated intrahepatic cholangiocarcinomas and its expression was more
      frequent in the hilar type. Cytokeratin 20 expression was observed in 17 (81%) of
      metastatic adenocarcinomas in liver from colorectal regions, to a lesser degree
      in those from gastric regions, and was rare in those from gallbladder and
      pancreatic regions; cytokeratin 7 showed a reverse expression pattern in these
      metastatic adenocarcinomas in liver. The profile of cytokeratins 7 and 20 of
      metastatic colorectal and gastric carcinomas differed from that for intrahepatic
      cholangiocarcinomas, while that of metastatic gallbladder and pancreatic
      carcinoma was similar to that for intrahepatic cholangiocarcinomas. Moreover,
      cytokeratin 18 and 19 expression was significantly infrequent in metastatic
      gastric carcinomas than in intrahepatic cholangiocarcinomas and metastatic
      colorectal carcinomas. CONCLUSION: The combined immunostaining of cytokeratins 7,
      18, 19 and 20 is useful for the characterization of intrahepatic
      cholangiocarcinomas with respect to histological subtypes and intrahepatic
      location. It helps to differentiate intrahepatic cholangiocarcinoma from
      metastatic adenocarcinomas in liver and from colorectal and gastric regions; it
      also indicates the primary focus metastatic adenocarcinomas in livers.

PMID- 10931220
TI  - Structural and cell surface antigen expression in the rete ovarii and epoophoron
      differs from that in the Fallopian tube and in endometriosis.
AB  - AIMS: We compared the immunohistochemical profiles of the rete ovarii and
      endometriosis in order to identify a panel which distinguishes between these
      structures. The immune profiles of the epoophoron, Fallopian tube and ovarian
      surface epithelium were also studied. MATERIALS AND METHODS: Twenty-four women
      with no evidence of endometriosis and seven who had endometriosis in the uterine
      adnexae were studied using nine antibodies to intermediate filament proteins and
      cell surface markers. None of the structures studied shared an identical profile
      of immunohistochemical reaction. The immunoprofile of endometriosis showed some
      similarities to that of the Fallopian tube, but differed from that of the rete
      ovarii, epoophoron and ovarian surface epithelium CONCLUSIONS: A panel including
      Ca-125, epithelial membrane antigen and the epithelial glycoprotein BerEp4 would
      permit the distinction between endometriosis and the rete ovarii in problematic
      cases. The study showed some commonality in reaction between endometriosis and
      the Fallopian tube which indicates that they may share a common (paramesonephric)
      origin. There was little commonality in the immunoprofile of endometriosis and
      the ovarian surface epithelium implying that endometriosis is unlikely to develop
      as a result of serosal metaplasia.

PMID- 10931221
TI  - Distinction between coeliac disease and refractory sprue: a simple
      immunohistochemical method.
AB  - AIMS: We recently showed that refractory sprue is distinct from coeliac disease,
      the former being characterized by abnormal intraepithelial T-lymphocytes
      expressing a cytoplasmic CD3 chain (CD3c), lacking CD3 and CD8 surface
      expression, and showing TCRgamma gene rearrangements. To take advantage of the
      abnormal phenotype of CD3c + CD8 - intraepithelial lymphocytes (IEL) in
      refractory sprue we developed a simple method to distinguish coeliac disease from
      refractory sprue. METHODS AND RESULTS: Comparative immunohistochemical studies
      using anti-CD3 and anti-CD8 antibodies were applied on paraffin-embedded and
      frozen biopsy specimens in refractory sprue (n = 6), coeliac disease (n = 10),
      healthy controls (n = 5) and suspected refractory sprue (n = 6). Comparable
      results were obtained on fixed and frozen biopsy specimens. In four of the six
      patients with suspected refractory sprue, abnormal CD3c + CD8 - IEL and TCRgamma
      gene rearrangements were found, as in refractory sprue; the remaining two
      patients had normal (CD3 + CD8 +) IEL and no TCRgamma gene rearrangements. Both
      patients had coeliac disease, as one failed to comply with a gluten-free diet,
      while the other was a slow responder. CONCLUSION: This simplified immunostaining
      method using anti-CD3 and anti-CD8 antibodies on paraffin sections can
      distinguish active coeliac disease from refractory sprue and should prove useful
      in clinical practice.

PMID- 10931223
TI  - Authors' reply

PMID- 10931222
TI  - Expression of VCAM-1, ICAM-1, E- and P-selectin and tumour-associated macrophages
      in renal cell carcinoma.
AB  - AIMS: Neoangiogenesis is accompanied by an increase in endothelial surface, which
      can support infiltration by immune cells depending on adhesion molecule
      expression. Therefore, the expression of cell adhesion molecules on microvessels
      and epithelial cells was analysed in renal cell carcinomas as compared to tumour
      free tissue. METHODS AND RESULTS: PECAM-1, CD34, ICAM-1, VCAM-1, VLA-4, P- and E
      selectin, the macrophage antigens Ki-M1P and Mac-1, and lymphocyte function
      antigen LFA-1 were identified immunohistochemically. VCAM-1, ICAM-1, and E
      selectin were equally or less expressed, whereas P-selectin was increased on
      microvessels in tumour tissue. The density of VCAM-1-positive tumour microvessels
      correlated positively with an advanced tumour stage and E- and P-selectin
      positive tumour microvessels with the amount of associated macrophages. The
      expression of ICAM-1 and VCAM-1 on neoplastic epithelia correlated with an
      increased density of macrophages and a minor degree of tumour differentiation.
      CONCLUSIONS: The positive correlation of macrophage infiltration and expression
      of cell adhesion molecules on tumour microvessels and epithelia with minor tumour
      differentiation and an advanced stage indicates that adhesion molecule expression
      is not associated with an effective antitumour function of macrophages

PMID- 10931224
TI  - Filaria in an axillary lymph node dissection specimen.

PMID- 10931225
TI  - High-grade squamous intraepithelial neoplasia in a Bartholin's gland cyst
      associated with HPV 16 infection.

PMID- 10931226
TI  - Hepatoid carcinoma of the lung: a case report with immunohistochemical,
      ultrastructural and in-situ hybridization findings.

PMID- 10931227
TI  - Hyalinizing clear cell carcinoma of the hypopharynx metastasizing to the lung: a
      case report.

PMID- 10931228
TI  - Intestinal T-cell lymphoma probably of CD8alphaalpha lymphocyte derivation.

PMID- 10931230
TI  - From this month's histopathology

PMID- 10931231
TI  - The diagnosis of dysplasia and malignancy in Barrett's oesophagus.
AB  - Barrett's metaplasia is associated with an increased risk for adenocarcinoma.
      Adenocarcinoma develops through a multistep process characterized by defects in
      genes and morphological abnormalities. The early morphological changes of the
      process are called 'dysplasia'. Dysplasia is defined as an unequivocal neoplastic
      (premalignant) transformation confined within the basement membrane. For most
      Western pathologists malignancy is defined as invasion and characterized by a
      breach through the basement membrane. Japanese pathologists rely on cytological
      atypia and complex branching of crypts. Cytological and architectural
      abnormalities allow identification of dysplasia on routinely stained sections. A
      distinction is made between low- and high-grade dysplasia. The differential
      diagnosis between low-grade dysplasia and reactive changes can be difficult.
      Therefore a second opinion is strongly recommended, not only for high-grade
      dysplasia but also for low-grade. Immunohistochemistry for p53 and flow cytometry
      for detection of aneuploidy can support the diagnosis. Identification of
      dysplasia and malignancy depends on the number of biopsy samples examined. The
      minimum number of biopsies required has not yet been determined and depends
      partly on the length of the metaplastic segment. It has been proposed to sample
      with four quadrant biopsies at 20-mm intervals. New endoscopic techniques can
      increase the diagnostic yield. Endoscopically visible lesions increase the risk
      of finding malignancy. The time sequence for the progression of dysplasia is not
      known but progression from low- to high-grade and cancer has been shown to occur
      over a period of years although it may not be inevitable.

PMID- 10931232
TI  - Immunohistochemical assessment of Ki67 and p53 expression assists the diagnosis
      and grading of ulcerative colitis-related dysplasia.
AB  - AIMS: To assess whether Ki67 and p53 immunostaining may assist the diagnosis and
      grading of ulcerative colitis-related dysplasia. METHODS AND RESULTS: Location of
      Ki67 staining and location and intensity of p53 staining were assessed in
      ulcerative colitis (UC) cases showing the features of high-grade dysplasia (HGD,
      n = 14), low-grade dysplasia (LGD, n = 22), 'indefinite for dysplasia' (n = 12),
      or regenerative atypia (RA, n = 22). Good intra- and inter-observer
      reproducibilities were demonstrated in the performance of these assessments. All
      the dysplasia cases showed extension of Ki67 staining above the basal third of
      the crypt. Moderate intensity p53 staining was seen in 10/22 RA cases, but strong
      intensity p53 staining was seen only in cases of dysplasia. All the cases of HGD
      showed extension of Ki67 and p53 staining above the basal two thirds of the
      crypt. CONCLUSIONS: Restriction of Ki67 staining to the basal third of the crypt
      appears to exclude a diagnosis of dysplasia whereas strong intensity p53 staining
      suggests a diagnosis of dysplasia. Restriction of Ki67 or p53 staining to the
      basal two-thirds of the crypt appears to exclude a diagnosis of HGD.

PMID- 10931233
TI  - Mandibular pseudocarcinomatous hyperplasia.
AB  - AIMS: Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous)
      hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are
      reported to highlight the differences with the various squamous neoplasms which
      occur in that site. METHODS AND RESULTS: In two patients carrying a mandibular
      graft following the excision of an ameloblastoma, mucosal ulcers resulted in
      chronic osteomyelitis. In a third patient, an apical dental infection was
      associated with fistulated osteomyelitis. Histology of the three sequestra showed
      an intraosseous squamous proliferation. It was characterized by a peripheral
      involvement of medullary spaces, the more mature epithelial layer covering the
      bone trabeculae without intervening stroma, and the basal type epithelial layer
      surrounding a central fibrovascular core. There were no histological or
      cytological signs of malignancy. CONCLUSION: PH shows an inverted pattern when
      compared with the centro-medullary tumoural islands seen in the various oral or
      odontogenic squamous neoplasms which occur in the jaws. The lack of signs of
      malignancy distinguish PH from common squamous cell carcinomas. A short clinical
      course is an important feature in the distinction of PH from the well
      differentiated squamous cell carcinomas which may develop in fistulated chronic
      osteomyelitis.

PMID- 10931234
TI  - Polymorphous low-grade adenocarcinoma and adenoid cystic carcinoma: distinct
      architectural composition revealed by collagen IV, laminin and their integrin
      ligands (alpha2beta1 and alpha3beta1).
AB  - AIMS: Polymorphous low-grade adenocarcinoma (PLGA) and adenoid cystic carcinoma
      (ACC) are malignant salivary gland tumours bearing many similar histological
      patterns. This study was undertaken to show how the presence and distribution of
      collagen IV and laminin, and their ligands (integrin alpha2beta1 and alpha3beta1
      components), can reveal histoarchitectural differences which distinguish these
      two entities. METHODS AND RESULTS: Five cases of ACC and five cases of PLGA from
      the archives of the Oral Pathology Department of the School of Dentistry of the
      Sao Paulo University were submitted to immunostaining with the antibodies to
      collagen IV, laminin, and integrins alpha2beta1 and alpha3beta1 using the
      streptavidin-biotin-peroxidase technique. Positive and negative controls were
      included. PLGA showed a thin line of collagen IV and laminin surrounding
      structures composed of a single cell layer. Integrins were expressed as a
      widespread and granular pattern. A thick line of collagen and laminin was
      observed around the neoplastic structures of ACC. Both integrins were expressed
      in intercellular spaces and around luminal spaces of tubular structures.
      CONCLUSIONS: Collagen IV and laminin, and their integrin ligands, are useful in
      demonstrating that neoplastic ductal units of PLGA are composed of a single cell
      layer, being distinct from ACC which contains structures composed of two layers
      of neoplastic cells.

PMID- 10931235
TI  - Association of Helicobacter pylori-dependent gastritis with gastric carcinomas in
      young Japanese patients: histopathological comparison of diffuse and intestinal
      type cancer cases.
AB  - AIMS: The causal relationship of H. pylori gastric colonization with gastric
      cancer development has not as yet been fully elucidated. The prevalence of H.
      pylori infection increases with age in the asymptomatic population in Japan, and
      reaches a high plateau in those older than 40 years. The objective of this study
      was to assess the link between H. pylori and gastric carcinomas in patients
      younger than 40 years. METHODS AND RESULTS: Detection of H. pylori and assessment
      of background mucosa based on the Sydney system was performed histopathologically
      for 40 Japanese gastric cancer cases younger than 40 years and compared with 40
      age- and sex-matched controls. H. pylori infection in gastric mucosa was detected
      significantly more frequently (P < 0.001) in patients with cancer (29/40; 72.5%)
      than in controls (11/40; 27.5%). Additionally, by histopathological comparison
      between intestinal (18 cases) and diffuse (70 cases) types of young gastric
      cancer patients, mucosal atrophy and intestinal metaplasia were found to coexist
      with acute and chronic inflammation in the background mucosa of both intestinal
      and diffuse types, being significantly more prevalent than in young controls.
      CONCLUSIONS: As well as the high prevalence of H. pylori in young subjects with
      gastric cancer, it is clear that persistent infection induces mucosal damage,
      resulting in atrophy and intestinal metaplasia. Thus, acute/chronic gastritis
      could play an essential role in the early development of neoplasia in the
      stomach.

PMID- 10931237
TI  - Uncommon histopathological findings in fatal measles infection: pancreatitis,
      sialoadenitis and thyroiditis.
AB  - AIMS: We report uncommon histopathological findings in fatal measles infection.
      METHODS AND RESULTS: We describe the autopsies of four patients who died during a
      measles outbreak in Sao Paulo, Brazil, in 1997. Two of the patients were children
      receiving chemotherapy for non-Hodgkin's lymphoma, one was an adult with acquired
      immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman.
      All patients had their deaths attributed to measles pneumonia. The autopsies
      revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute
      pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles
      antigen was detected in lung tissue using a monoclonal anti-measles antibody.
      CONCLUSIONS: : Pancreatitis, thyroiditis and sialoadenitis are not previously
      reported histopathological findings in measles infection. Pancreatitis is a
      potentially severe complication and should be considered when treating patients
      with atypical measles.

PMID- 10931236
TI  - When can complete regression of low-grade gastric lymphoma of mucosa-associated
      lymphoid tissue be predicted after helicobacter pylori eradication?
AB  - AIMS: Recent studies suggest that primary low-grade gastric lymphomas of mucosa
      associated lymphoid tissue (MALT) are cured in many cases between 1 and 18 months
      after H. pylori eradication. The aim of this study is to elucidate when complete
      regression (CR) of MALT lymphoma can be histologically predicted after H. pylori
      eradication. METHODS AND RESULTS: Twenty-one patients with low-grade gastric MALT
      lymphoma were treated with triple therapy (amoxicillin, clarythromycin and proton
      pump inhibitor) for 14 days. Subsequently, they were followed up by sequential
      endoscopy and biopsy (number of biopsy specimens for each endoscopy is 3-8, with
      an average of 4) from 91 to 657 days (average: 309 +/- 165 days). Eradication of
      H. pylori infection was achieved in all patients. Nine patients were free of
      lymphoma at 1 to 2 months after eradication and remained in CR at 163-657 days.
      Twelve patients showed residual lymphoma at 1 to 2 months after eradication. Five
      out of 12 patients revealed only one or two small foci of lymphoma-cell
      aggregation and showed a high incidence (80%) of CR at the latest biopsy (135-434
      days, average 276 +/- 115 days after eradication), while seven patients showed
      diffuse remains of lymphoma cells and indicated CR in only one case (14%) at 362
      days, partial regression in five cases at 130-431 days (average 227 +/- 114
      days), and no change in one case at 91 days after eradication. CONCLUSIONS: :
      These results suggest that CR of low-grade MALT lymphoma can be predicted at 1 to
      2 months after eradication therapy by checking histological changes of MALT
      lymphoma cells.

PMID- 10931238
TI  - Microcystic adenoma of the pancreas (glycogen-rich cystadenoma) with stromal
      amyloid deposits.
AB  - AIMS: We report a case of a pancreatic glycogen-rich microcystic serous adenoma
      with stromal amyloid deposits, focusing on the significance of isolated amyloid
      deposits in tumours. METHODS AND RESULTS: The architectural pattern was
      characterized by thin-walled cysts lined by a single layer of flat or cuboidal
      epithelial cells intensely stained by the PAS-reaction only before diastase
      digestion, suggesting the presence of glycogen. Tumour stroma was composed of
      broad fibrocollagenous tissue with lamellar hyalinized areas which were
      positively stained by Congo red and showed green birefringence and dichroism with
      polarized light. For amyloid protein characterization, immunohistochemical
      studies were performed with anti-beta amyloid protein and anti-amyloid precursor
      pre-A4695. The former antibody diffusely stained tumour stroma, while the latter
      stained only scattered stroma cells. CONCLUSIONS: This is the first documented
      case of amyloid deposition in pancreatic serous adenoma. We indicate that the
      source of amyloid is an APP-like precursor secreted by stromal myofibroblasts.

PMID- 10931239
TI  - Primary malignant gonadal mesotheliomas and asbestos.
AB  - AIMS: The clinicopathological, immunohistochemical and aetiological aspects, with
      respect to asbestos, of seven primary gonadal mesotheliomas (three
      intratesticular, four ovarian) are described and compared. These tumours are
      extremely rare, poorly described and the knowledge of their natural history is
      very limited. METHODS AND RESULTS: The cases were collated from the UK Health and
      Safety Executive Mesothelioma Register over a 24-year period (1968-91). Primary
      mesotheliomas of the tunica vaginalis and ovary comprised 0. 09% (10 cases) and
      0.03% (three cases) of mesothelioma deaths, respectively. No primary
      intratesticular (non-tunica vaginalis) malignant mesotheliomas have been
      described. In this study, we present seven (three intratesticular, four ovarian)
      primary malignant gonadal mesotheliomas. In both genders the tumours show a
      similar age distribution (with median onset in the sixth decade), a similar
      association with asbestos (in approximately 50% cases), a diverse histological
      spectrum (with predominantly tubulopapillary epithelial subtype tumours) and an
      immunophenotype that is comparable with malignant pleural and peritoneal
      mesothelioma. The clinical course appears variable (mean, 26 months; range, 9-50
      months). All tumours in the study presented as localized masses and their
      prognosis appeared more favourable than that of diffuse pleural and peritoneal
      cases. CONCLUSIONS: An awareness of the existence of these rare forms of
      malignant mesothelioma is important to prevent misdiagnosis. Immunohistochemistry
      has an important role in confirmation of the diagnosis. The accurate diagnosis of
      primary gonadal mesothelioma has potentially important medicolegal compensation
      considerations as a significant proportion of these cases are associated with
      asbestos.

PMID- 10931240
TI  - Central neurocytomas are genetically distinct from oligodendrogliomas and
      neuroblastomas.
AB  - AIMS: Central neurocytoma is a rare central nervous system tumour typically found
      in the lateral ventricles and at the septum pellucidum. Histologically, it
      resembles oligodendrogliomas and yet ultrastructurally, it shows neuronal
      differentiation. Its molecular oncogenesis is not known. The aim of this study
      was to examine whether major genetic events found in oligodendrogliomas and
      neuronal tumours, namely allelic deletions of chromosomes 1p and 19q and N-myc
      amplification, can be found in central neurocytomas. As there was one report
      describing gain of chromosome 7 in central neurocytomas, we also examined
      epidermal growth factor receptor (EGFR) amplification, as the EGFR gene is
      located at chromosome 7p. METHODS AND RESULTS: Nine central neurocytomas and
      matched blood samples were examined for loss of heterozygosity (LOH) of 1p and
      19q13.2-13.4 with 23 finely mapped microsatellite markers. N-myc amplification
      was studied by fluorescence in-situ hybridization using paraffin-embedded
      sections. EGFR amplification was tested for by differential PCR. Six of nine
      (67%) tumours showed LOH at one or more loci at 1p and 5/9 (56%) of cases showed
      LOH at 19q. However, common regions of deletion cannot be identified. The
      majority of informative markers are retained at 1p (84%) and 19q (86%). Only one
      tumour showed amplification of N-myc and none of the cases showed amplification
      of EGFR. CONCLUSION: Central neurocytomas are genetically distinct from
      oligodendrogliomas, and chromosomes 1p and 19q probably do not play an important
      role in their pathogenesis. N-myc and EGFR amplification are rare.

PMID- 10931241
TI  - CD44 isoform expression in synovial sarcoma correlates with epitheliogenesis but
      not prognosis.
AB  - AIMS: We immunohistochemically determined the expression of CD44 standard and
      splice variant isoforms in a series of synovial sarcomas and sought correlations
      with histological subtype and clinical parameters including outcome. METHODS AND
      RESULTS: From 39 patients, a total of 56 formalin-fixed and paraffin-embedded
      tumour samples (including initial, recurrent and metastatic tumours) were used to
      immunohistochemically evaluate the expression of epitopes encoded by CD44s and
      the CD44 splice variants CD44v3-v10. Significance of proposed prognostic
      indicators was evaluated in relation to the survival, time to local recurrence
      and time to metastases using log-rank analysis. Sixty-four percent of synovial
      sarcomas expressed CD44s and 46% expressed CD44v3-v10 (var). Synovial sarcomas
      with epithelial or epithelioid areas preferentially expressed CD44s in these
      areas when compared with the spindle cell element. There were no correlations
      with clinical parameters or outcome. CONCLUSION: The expression of CD44 was not
      found to correlate with survival, local recurrence or metastatic ability. In
      synovial sarcoma, CD44 and variant isoform expression appears to be associated
      with the degree of epithelial differentiation. CD44 expression in synovial
      sarcoma shows interesting similarities to CD44 expression in embryological
      epitheliogenesis.

PMID- 10931242
TI  - The cytokeratin profile of medullary carcinoma of the breast.
AB  - AIMS: The cytokeratin (CK) phenotype and vimentin expression of 31 medullary
      carcinomas was studied using commercially available antibodies on archived
      material. Comparing the phenotype of typical and atypical tumours and the
      phenotype of metastases, the biological significance of cytokeratin and vimentin
      expression in medullary carcinomas of the breast was determined. METHODS AND
      RESULTS: Antibodies to CK4, CK5 and 6, CK7, CK14, CK8 and 18, CK19, CK20 and to
      vimentin were used. All the typical and atypical medullary carcinomas and the
      metastases (10 cases) stained negatively for CK4 and positively for CK8-18
      (CAM5.2). Almost all the tumours were CK7 and CK19 positive and CK20 negative.
      Twelve per cent of the tumours contained CK14. Twenty-five per cent of the
      typical, 43% of the atypical and 20% of the metastatic medullary carcinomas
      showed CK5-6 positivity. No association between the cytokeratin-vimentin profile
      of the tumours and axillary node metastases, tumour size or oestrogen receptor
      status was found but instability of CK expression was demonstrated by comparing
      the primary tumours with their metastases. CONCLUSIONS: : Medullary carcinomas of
      the breast express all the glandular type CKs including CK19 and additionally a
      proportion of the tumours expresses some of the CKs typical for myoepithelial
      cells. There was no correlation with prognostic factors.

PMID- 10931243
TI  - Medullary carcinoma of the breast and BRCA1 mutation.

PMID- 10931244
TI  - Massive hepatic haemosiderosis in Wilson's disease.

PMID- 10931245
TI  - Solitary fibrous tumour of the breast: distinction from myofibroblastoma.

PMID- 10931247
TI  - Is T-cadherin (CDH13, H-cadherin) expression related to lung metastasis of
      osteosarcoma?

PMID- 10931246
TI  - Kaposi's sarcoma-like pyogenic granuloma.

PMID- 10931248
TI  - A century of controversy regarding the benefit or detriment of occlusal contacts
      on the mediotrusive side.
AB  - Many opinions have been presented in the literature during the past century
      regarding so-called mediotrusive/balancing/non-working side contacts. During the
      first half of this century, most authors advocated the advantage of these
      contacts (it was more or less the state of the art in prosthetic treatments),
      while during the last 50 years mediotrusive side contacts/interferences have
      mostly been regarded as a disturbing factor in the functioning of the mandible.
      Recently, it has been proposed that mediotrusive side contacts have a protective
      effect on the temporomandibular joint (TMJ). The aim of this study was to review
      opinions advocated during the twentieth century regarding the advantages and
      disadvantages of having contacts on the mediotrusive side during lateral
      excursions of the mandible. We conclude that, at present, there is no uniform
      body of scientific evidence supporting a balanced occlusion in favour of a
      mutually protective occlusion or vice versa. Longitudinal studies based on
      cohorts with different types of occlusal contacts, estimating the risk among
      these of developing signs and symptoms of temporomandibular disorders, are
      generally lacking and could provide valuable knowledge in this field.

PMID- 10931249
TI  - The effect of pH on the corrosion of dental metal alloys.
AB  - The aim of this study was to determine the effects of the oral environment's pH
      on the corrosion of dental metals and alloys that have different compositions,
      using electrochemical methods. The corrosion rates and the cathodic Tafel slopes
      were obtained from the current-potential curves. The effect of pH on the
      corrosion of dental metals and alloys was dependent on their composition.
      Dissolution of the ions occurred in all of the tested pH states. The dissolution
      was moderately low for samples containing titanium because its surface was
      covered with a protective layer, whereas the dissolution was maximal for the
      samples containing tin and copper. Addition of cobalt and molybdenum to the
      alloys improved their corrosion resistance; these cobalt and molybdenum alloys
      were not effected by changes in the pH. Dissolution of the precious metal alloys
      increased as the percentage of noble metals increased. The corrosion
      characteristics of dental metals and alloys are important because the corrosion
      tendencies of dental alloys in the mouth may cause health hazards, weakening and
      the aesthetic loss of dental restorations.

PMID- 10931250
TI  - Fluoride ion diffusion from a glass-ionomer cement.
AB  - The aims of this study were to observe the release of fluoride ions (F-) from GC
      Fuji Lining-LC(R) glass-ionomer cement, to assess the diffusion process, and to
      measure fluoride diffusivity (D) in the set cement. Specimens of various
      dimensions and shapes, ranging from discs to cylindrical rods, were fabricated
      for both open and embedded modes of testing. In the open mode studies, specimens
      with different surface to volume ratios were selected and immersed in 37 degrees
      C distilled water. In the embedded mode studies, only one diametral surface of
      the rod-shaped specimens of different lengths and diameters was exposed. F-
      concentration was measured using a fluoride electrode. The storage solution was
      analysed at predetermined intervals hourly, daily, and weekly (up to 10 weeks).
      Immediately after each sampling, the old storage solution was discarded and
      replaced with new distilled water. F- release from the set cements was detectable
      (0.4-3.8 ppm, varied with sample geometry), even after a 10-week sampling
      interval. F- release was greater in ground set cements (0.37 ppm/mg powder) than
      in control samples of unmixed powder (0.01 ppm/mg powder) immersed for 1 h. Two
      mechanisms for F- release were proposed. One was short-term and involved rapid
      dissolution from the cement surface. The other was more gradual and resulted in
      the sustained diffusion of ions through the bulk cement, which can be modelled by
      applying a mathematical technique known as separation of variables to Fick's
      Second Law of Diffusion. The mean D of F- in embedded set cements of glass
      ionomer was (1.4+/-0.5)x10-11 cm2/s, with higher apparent D observed in open mode
      samples [(7.6+/-1.4)x10-11 cm2/s].

PMID- 10931251
TI  - The effect of oestrogen deficiency on the alveolar bone resorption caused by
      traumatic occlusion.
AB  - This study, using 132 female rats, was designed to investigate whether oestrogen
      loss facilitates alveolar bone alterations induced by traumatic occlusion. Rats
      were ovariectomized (OVX) or underwent sham-operation (Sham). Seven days after
      surgery, half of the rats in each group were subjected to experimental traumatic
      occlusion (trauma), and the other half were left untreated. Thus, there were four
      groups: OVX+trauma, Sham+trauma, OVX, and Sham. Rats in each group were killed 1,
      3, 5, 7, or 10 days after the introduction of occlusal trauma. The resected
      mandibles were processed without decalcification, and histomorphometric
      measurements were performed in the alveolar bone adjacent to the periodontal
      ligament of the first molar. The statistical assessment of the time- and group
      specific differences by analysis of variance revealed significant differences
      between the OVX+trauma and Sham+trauma groups in the resorption parameters, but
      not in the formation parameters. The results show that the alveolar bone dynamics
      induced by traumatic occlusion are enhanced by oestrogen deficiency.

PMID- 10931252
TI  - Comparison of in vitro fracture strength of metallic and tooth-coloured posts and
      cores.
AB  - In root-treated anterior teeth a better aesthetic can be achieved by using
      translucent and tooth-coloured post and core restorations instead of traditional
      metal post systems. The aim of this in vitro study was to compare the fracture
      strength of tooth-coloured ceramic and fibre-reinforced posts as well as titanium
      posts with clinically proven gold alloy posts as a control. Two all-ceramic, one
      gold alloy and three combined post restoration systems (titanium and ceramic,
      respectively, fibre-reinforced posts with composite core) were each applied to
      upper incisors and after thermal cycling and mechanical loading (TCML) the
      fracture strength was determined. The variant providing the most reliable
      fracture strength values and the experimental fibre-reinforced composite (FRC)
      posts were - in combination with adhesively luted crowns - used to determine the
      fracture strength of the restoration after thermal cycling and mechanical
      loading. The median fracture strength of the luted posts and cores fluctuated
      between 114 and 546 N. Posts with composite cores demonstrate a higher fracture
      strength in comparison to the all-ceramic and gold alloy systems. Typical failure
      of metal systems was marked by loosening of the bonding and pulling out of the
      post in contrast to fracture of the ceramic posts. After the application of the
      crowns the ceramic system with composite core provided a fracture strength of 338
      N and the FRC system a fracture strength of 228 N. Regarding fracture strength,
      the ceramic posts with composite cores are an alternative to commonly used gold
      posts and cores. A standardized technical manufacture of FRC posts and cores
      would provide better fracture strength results of this new dental material. Post
      and core restorations with tooth-coloured, translucent material offer an improved
      aesthetic especially in anterior restorations. Because of the high fracture
      strength prefabricated ceramic posts in combination with composite cores should
      prove their clinical applicability.

PMID- 10931253
TI  - Patients' satisfaction in two long-term clinical studies on resin-bonded bridges.
AB  - This study aimed to evaluate patients' satisfaction with resin-bonded bridges and
      the effect of failures on the degree of satisfaction. In two clinical trials, 358
      patients completed guided questionnaires at regular recalls (n=1484). In this
      way, data regarding 'overall function', 'colour', 'shape', 'functional changes',
      'complaints' and 'recommendation to other patients' were obtained. The scores of
      each criterion were evaluated for the variables 'trial', 'gender', 'time after
      placement' and 'failure', using 4-way ANOVA. Encountered failures were rated
      using a 'failure severity scale'. For all combinations of measurement periods,
      the changes in patient's opinions were calculated and the differences tested
      using the paired t-test. Overall satisfaction was correlated with 'colour',
      'shape' and inversely correlated with 'complaints' (r>0.34; all P<0.005). No
      statistical differences were found between males and females. No significant
      changes were observed in patient satisfaction over time. Failures influenced the
      failure sensitive variables 'functional changes' and 'avoidance of load'. The z
      scores were independent of the severity of the failures (r<0.13; all P>0. 10).
      The degree of patient satisfaction with resin-bonded bridges appeared to be high
      and did not seem to be influenced by the occurrence of failure.

PMID- 10931254
TI  - Crimping of collagen in the intra-articular disc of the temporomandibular joint:
      a comparative study.
AB  - Very occasional reference is made to the presence of collagen crimps in the fibre
      bundles of the intra-articular disc (IAD) of the temporomandibular joint (TMJ).
      As the crimp structure may confer important biomechanical properties on the IAD,
      the present study was undertaken to determine its distribution in a variety of
      mammals, including humans. IADs from the rat, rabbit, guinea pig, ferret, sheep,
      marmoset and human were either sectioned or examined as whole mount preparations
      with polarized light. Apart from the guinea pig, where fibre bundles in the
      central region of the disc showed considerable overlap and masking of the crimp
      structure, the anteroposterior aligned fibres in the central region of all
      remaining animals showed the conspicuous presence of crimps. The periodicity of
      the crimp distance varied between about 10 and 30 microm. There was variation of
      the crimp periodicity between animals and between regions of the same disc. The
      crimping was associated with undulations along the length of the collagen fibres
      visible at the light microscope level using routine staining. The possible
      significance of crimping in association with internal derangement is discussed.

PMID- 10931255
TI  - Generalized joint laxity and its relation with oral habits and temporomandibular
      disorders in adolescent girls.
AB  - A group of 248 girls, aged 15-16 years, were randomly selected and examined both
      clinically and by questionnaire with regard to the signs and symptoms of
      temporomandibular disorders (TMD), generalized joint laxity (GJL), range of
      mandibular opening, temporomandibular joint (TMJ) hypermobility and presence of
      oral parafunctions. The prevalence of GJL was 43% and that of TMJ hypermobility
      (TMJH) was 27.3%. A significant, albeit weak, correlation was found between the
      two. In the presence of joint click, both active and passive opening were
      significantly larger. When either muscle or joint sensitivity to palpation was
      present, the difference between the active and passive range of mouth opening
      increased significantly. The presence of reported clicks was negatively
      associated with GJL. This association was not valid in the presence of
      parafunction. Some of the signs and symptoms of TMD affected the range of mouth
      opening. In the presence of joint clicks, the mean active and passive mandibular
      opening were significantly larger. In the presence of joint and muscle
      sensitivity to palpation, the difference between passive and active mouth opening
      was larger. This was possibly because of the effect of pain on the full active
      range of opening, which was invalid in the registration of the passive mandibular
      opening. GJL, when present, did not seem to jeopardize the health of the
      stomatognathic system as expressed in the signs and symptoms of TMD. There was a
      negative association between GJL and the presence of reported joint clicks and
      catch. When a parafunction was present in addition to GJL, this association was
      invalid but not reversed, as has been previously reported.

PMID- 10931256
TI  - Influence of formaline cresol on bond strength of adhesive luting agents to
      dentin.
AB  - The present study investigates the influence of the pulpotomy agent formaline
      cresol (FC) on bond strength between dentin and five adhesive systems (Super-Bond
      C&B, Bistite II, Imperva Dual Set, Panavia 21, and Panavia 21 with AD Gel). After
      the dentin surfaces of 75 bovine teeth (including 25 control samples) were
      exposed by grinding, 25 of the samples were soaked in FC for 2 days, and 25
      samples were soaked for 7 days. Samples were bonded to acrylic rods using five
      adhesive systems, and tensile bond strengths were determined after 1-day
      immersion in water. Data were analysed by analysis of variance and Duncan's new
      multiple range test, and the fractured surfaces were observed through a scanning
      electron microscope. The bond strengths were found to be influenced by the type
      of system, soaking period, and their combination. The bond strength values of
      three adhesive systems (Super-Bond C&B, Imperva Dual Set Bistite II, and Panavia
      21 with AD Gel) decreased after soaking in FC. After 7 days of FC exposure, the
      highest bond strength (9.8+/-2.9 MPa) was obtained with the Super-Bond C&B
      system.

PMID- 10931257
TI  - Comparison of the transfer precision of three different impression materials in
      combination with transfer caps for the Frialit-2 system.
AB  - Transfer of the precise position of implants to a master cast is a prerequisite
      for accurate and passive fit of the superstructure. Implants lack the mobility of
      natural teeth and, therefore, inaccurate frameworks result in stress within the
      mechanical parts and the implant-bone interface. Various impression methods have
      been described to achieve accurate reproduction of the intra-oral relation of the
      implants. The aim of this experimental study was to compare three different
      impression materials (polyether, polyvinyl siloxane, hydrocolloid) with the
      Frialit(R)-2 system and with the indirect technique. In addition, the use of
      transfer caps (TCs) to improve transfer precision was tested with all three
      materials. All measurements were performed using a three-dimensional (3D) co
      ordinate measuring machine that is capable of locating points in space and
      calculating the relative distortions as angles of tilt (rot-XY, rot-XZ, rot-YZ)
      and 3D displacement. The results suggest that addition-silicone (a-silicone) and
      polyether are the materials of choice for implant transfer procedures. The use of
      TCs resulted in a significantly reduced rotation in the XY-plane but did not
      improve the absolute 3D displacement. A-silicone with the use of TCs proved to be
      most precise. Comparison between polyether and polyvinyl siloxane showed
      significant differences in the XY-rotation and the 3D displacement in favour of
      the silicone. Because the mean distortions between the original model and the
      master casts were about 100 microm, absolutely precise fit may be unattainable
      owing to the physical properties of the materials. Further studies will have to
      evaluate the amount of tolerable stress at the implant-bone interface.

PMID- 10931258
TI  - The relationship between dentofacial morphology and the isometric jaw-opening and
      closing muscle function as evaluated by electromyography.
AB  - The purpose of this study was to clarify the relationship between the dentofacial
      morphology and masticatory muscle function in both isometric jaw-opening and
      closing. The subjects consisted of 26 male adults without masticatory
      dysfunction. Electromyograms were obtained from the digastric and masseter
      muscles to evaluate their muscle activities. The sum energy, median frequency,
      and equilibrium index were calculated as parameters of the muscle activity. A
      correlation analysis was performed between the parameters for the muscle activity
      and the dentofacial morphology on lateral roentgenographic cephalograms. The sum
      energy in the jaw-closing muscle showed a significant relationship with the
      gonial angle, mandibular length, and facial height, but not in the jaw-opening
      muscle. A median frequency in the jaw-opening muscle showed a significant
      relationship with size and position of the mandible, and also that in the jaw
      closing muscle with the mandibular plane angle, facial height, and mandibular
      body length. Furthermore, the equilibrium index of the median frequency was
      related to the facial height, mandibular length, and inclination of the
      mandibular incisor. In conclusion, the dentofacial morphology was found to be
      closely related to the muscle activity not only of the jaw-closing muscle but
      also of the jaw-opening muscle during isometric muscle contraction.

PMID- 10931259
TI  - Need for occlusal therapy and prosthodontic treatment in the management of
      temporomandibular disorders. Part II: Tooth loss and prosthodontic treatment.
AB  - The second part of this review, evaluating the literature on the relationship
      between dental occlusion and temporomandibular disorders (TMDs), focuses on the
      aetiological importance of tooth loss and the place of prosthodontic replacement
      in the treatment of TMD. Loss of teeth and lack of posterior occlusal support
      seem to have little influence on the development of TMD, which calls into
      question the use of prosthodontic restoration as prevention or treatment for TMD.
      In addition, there are practically no studies assessing the benefit of
      instrumental analysis in diagnosis or comparing the outcome of prosthodontic
      treatment with simple reversible methods in the management of TMD. There is a
      trend in the current literature to abandon any treatment, including positioning
      appliances and prosthodontic measures, to 'recapture the disk' in patients with
      disk displacements because of the favourable, long-term results achieved after
      using more simple methods. It is concluded that prosthetic therapy in TMD
      patients is not appropriate for initial TMD treatment and should only be carried
      out on prosthodontic indications after reversible treatment has alleviated pain
      and dysfunction.

PMID- 10931260
TI  - Finite element analysis of stress relaxation in soft denture liner.
AB  - To gather knowledge related to establishing criteria for selecting soft denture
      liners for individual patients, the effects of certain properties of soft denture
      liners on stress distribution were evaluated by two-dimensional finite element
      analysis. A partial mandibular edentulous ridge crest was modelled. Six
      combinations of thickness (mucosa: 1 or 2 mm; soft denture liner: 1, 2, or 3 mm)
      and 18 combinations of Young's modulus (mucosa: three kinds; soft denture liner:
      six kinds) were analysed. The ratio of maximum to minimum stress in the mucosa
      (stress ratio) was calculated to estimate stress concentration. In the case of
      thin mucosa (1 mm thickness), the lower the Young's modulus of the soft denture
      liner, the lower the stress ratio. However, if the soft denture liner had a lower
      Young's modulus than the mucosa, stress concentrated adversely. These results
      suggest that the elasticity of the soft denture liner should match the elasticity
      of the mucosa to obtain the optimum cushioning effect.

PMID- 10931261
TI  - Genioglossus muscle activity during rhythmic open-close jaw movements.
AB  - The purpose of this study was to examine genioglossus muscle activity during
      rhythmic open-close jaw movements. The electromyographic activity of the
      genioglossus muscle was recorded with a bipolar fine-wire electrode in six
      healthy males. The electromyographic activities of the ipsilateral masseter and
      digastric muscles were simultaneously recorded with bipolar surface electrodes.
      The subjects were instructed to perform rhythmic open-close jaw movements in time
      with a metronome set at 23, 27, 33, 42 and 50 beats/min. In all of the subjects,
      rhythmic electromyographic activity of the genioglossus muscle was recorded in
      both the jaw-opening and jaw-closing phases. The activity of the genioglossus
      muscle was predominantly recorded in the jaw-opening phase in two subjects, and
      in the jaw-closing phase in two subjects. The burst duration of the
      electromyographic activity of the genioglossus muscle changed linearly in
      accordance with the cycle duration. However, the latency from the onset of the
      electromyographic activity of the masseter or digastric muscle to that of the
      genioglossus muscle was almost constant, independent of the cycle duration. Based
      on these findings, we conclude that the activity of the human genioglossus muscle
      is closely linked to that of masticatory muscles under the control of a closely
      related central pattern generator.

PMID- 10931262
TI  - Bilateral investigation of the temporomandibular joint. An autopsy study of
      edentulous individuals.
AB  - Investigations concerning normal and pathological anatomy of the
      temporomandibular joint (TMJ) have shown that pathological reactions such as
      deviations of the shape of the condyle, disc thinnings, disc perforations and
      osteoarthrotic changes are fairly common, particularly in the elderly population.
      Autopsy studies of the TMJ describe pathological findings respective to their
      location in different age groups, but most authors describe their findings for
      removed joints of one side only. The specific aim of this study was therefore to
      investigate the intra-individual relationships between the degenerative changes
      and deviations concerning the articular surfaces of the TMJs and the
      topographical distributions of these findings. In this investigation both joints
      of 22 edentulous individuals between 58 and 95 years of age were studied.
      Correlations were found between the right and left joints with respect to the
      anatomical location of the pathological findings.

PMID- 10931263
TI  - Computer aided gnathosonic analysis: distinguishing between single and multiple
      tooth impact sounds.
AB  - Watt developed a classification of tooth contact sounds that distinguished
      between the short sharp, reproducible sounds heard when the teeth meet
      simultaneously and the dull prolonged, poorly reproducible sounds heard when
      tooth contacts are sequential. However, when a large occlusal prematurity, for
      instance a high restoration, is introduced, tooth contact sounds are also short
      sharp and highly reproducible. In this study, a method of distinguishing single
      from multiple tooth contact sounds is described, based on an analysis of the
      phase and amplitude of sounds detected by headphones placed over the ears.

PMID- 10931264
TI  - Flexural strength of rebased denture polymers.
AB  - The properties of denture base and reline resins may be affected by daily changes
      between room temperature and mouth temperature. The purpose of the study was to
      evaluate the effect of thermocycling on the flexural strength of the relined
      denture base polymer with reline resin. Three denture base resins, three hard
      reline resins and their combinations were tested. Fourteen specimens, 65x10x2.5
      mm, were fabricated for each material. Polymer combination specimens were made
      using 1.5 mm hard reline resin on 1.0 mm cured denture base resins. Half of the
      specimens were stored for 50+/-2 h in distilled water at 37 degrees C, while the
      other half were thermocycled for 20 000 cycles between 4 and 60 degrees C. Three
      point bending tests were conducted on a universal testing machine at a cross-head
      speed of 0.5 cm/s. The flexural strengths were measured and a statistical
      analysis was performed on the data using three-way ANOVA (P<0.05). The results
      showed that the flexural strength of relined denture base polymer was
      significantly higher than that of hard reline polymer. Thermocycling did not
      affect the flexural strength of the relined denture base polymers, whereas the
      denture base polymer and reline polymer alone showed a decrease in strength after
      thermocycling.

PMID- 10931265
TI  - Mandibular positions and jaw-closing muscle activity during sleep.
AB  - The aim of this study was to clarify the relationship between the mandibular
      position with tooth contacts and jaw-closing muscle activity during sleep using
      electromyography and newly devised equipment for detecting tooth contacts and
      also to confirm the validity of this system. Five males volunteered for this
      study and three of them reported their bruxing during sleep. Occurrences of tooth
      contacts at eccentric mandibular positions in addition to the intercuspal
      position during sleep were detected using micro photo sensors and sensor targets
      prepared for the individuals. Electromyographic activities (EMG) from right and
      left masseter and anterior temporal muscles were also recorded. Results of the
      polygraphic recordings demonstrated that the mandibular positions during bruxism
      could be distinguished clearly whether it's in the right or left position, or has
      no lateral deviation, and further, that bruxing events could be categorized based
      on mandibular position pattern. The relationship between the mandibular position
      and muscle activity could be evaluated using this system. The study suggested the
      validity of the system for measuring nocturnal bruxing events.

PMID- 10931266
TI  - Vibrating-traction method for mechanical joint distraction.
AB  - Mechanical static traction has been adopted as one of the treatment procedures
      for joint diseases and fractures. The effect of mechanical vibration on the
      mechanical traction of the temporomandibular joint was studied in six human
      subjects. A mechanical traction force of 2000 gf was applied as a dynamic
      traction force with mechanical vibration or as a static traction force. The
      dynamic traction force with vibration was applied for 5 min to the right
      temporomandibular joint using a vibrating-traction apparatus which generated
      mechanical vibrations of 1000, 3000 or 4000 Hz. Application of a static traction
      force for 5 min was used as a control condition. Vertical condylar displacement
      was mathematically evaluated from the deviation of the mandible using Eddy
      current displacement sensors which were attached to the maxillary dental arch.
      Among the three vibration frequencies, 3000 Hz resulted in the maximum vertical
      condylar displacement for all six subjects, showing the mean condylar
      displacement of 668+/-242 microm. In contrast, vibrations of 1000 and 4000 Hz
      showed a smaller traction effect. Application of the static traction force for 5
      min resulted in a mean vertical condylar displacement of 5.7+/-4.9 microm,
      showing almost no traction effect to the joint. From the results of this study,
      it was revealed that vibrating traction could distract a joint more effectively
      than could static traction and that the traction force necessary for effective
      vibrating traction was less than that for static traction.

PMID- 10931267
TI  - Presence of microorganisms on the fitting denture complete surface: study 'in
      vivo'.
AB  - It was the intention to study if glazing the fitting surface of maxillary
      dentures with a light-curing acrylic resin would diminish the bacterial counts.
      The study included the application of a photopolymerizing glaze to one half of
      the fitting denture surface; after 15 days microbial plaque was collected from a
      1 cm2 area of the glazed and the untreated resin, respectively. At the same time
      bacteria were collected from a 1 cm2 area of the corresponding sites on the
      palatal mucosa. The application of the glaze had modified the number of bacteria
      cultured from the glazed surface versus the untreated surface. Denture surface:
      total aerobic bacteria, 1:4; aerobic streptococci, 1:4; aerobic staphylococci,
      1:5; anaerobic bacteria, 1:3.5; mucosal surface aerobic bacteria, 1:4;
      streptococcal, 1:4. The differences were statistically significant at P<0.002.
      However, from a quantitative and qualitative point of view these differences were
      minor compared with the actual concentrations of the microorganisms of 104
      106/cm2 observed on the fitting denture surface and the palatal mucosa.

PMID- 10931268
TI  - Clinical rest and closest speech positions in the determination of occlusal
      vertical dimension.
AB  - Two subject groups had their mandibular positions determined, using an
      electrognathograph, at the clinical rest position (CRP) and at the closest
      speaking position (CSP). They were classified into a toothwear (largely of
      attritional origin) group (n=30) and a non-toothwear, or normal, group (n=60).
      The mean CRP deduced for the groups was similar in all three dimensions and found
      to be just less than 2 mm open from and 0.6 mm posterior to intercuspal position
      (IP) and approximately in the midline. The CSP, in two dimensions, of the
      toothwear group was significantly closer to IP than that of the normal group. The
      vertical component of CRP and CSP was similar for the normal group but CSP was
      significantly reduced in comparison to CRP for the toothwear group. The most
      forward component of CSP was significantly more anteriorly placed than was that
      of CRP. Although there was a pronounced inter-individual variation the results
      suggest toothwear, of long acting aetiology, has less affect on CRP than on CSP.

PMID- 10931269
TI  - Myogenous temporomandibular disorder patients and the temporomandibular opening
      index.
AB  - Limited mandibular movement is one of the cardinal signs of temporomandibular
      disorders, and is usually assessed by measurement of mouth opening. Linear
      measurement of mouth opening does not discriminate between diagnostic groups and
      has been shown to be influenced by gender, age and ramus length. A new
      temporomandibular opening index, however, can differentiate between diagnostic
      groups and is not influenced by the above variables. When patients with a
      myogenous temporomandibular disorder were examined, the temporomandibular opening
      index distinguished two subgroups, the first with values about the lower quartile
      and the second with values about the upper quartile. A similar identification of
      two subgroups was seen in electromyographic studies of myogenous
      temporomandibular disorder patients.

PMID- 10931270
TI  - Spectral characteristics of hypernasality in maxillectomy patients.
AB  - To reveal the acoustic characteristics associated with hypernasality and to
      ascertain their correlation to the severity of hypernasality, 30 speech samples
      produced by 15 maxillectomy patients were acoustically analysed with and without
      an obturator prosthesis in place. The isolated, sustained Japanese vowel /i/ was
      used as the stimulus for acoustic measurement and perceptual judgment to evaluate
      the severity of hypernasality. Normalized 1/3-octave spectral analysis
      demonstrated the spectral characteristics of hypernasality as a rise in amplitude
      between the first and second formants around the 1 kHz region, and a reduction in
      amplitude of the frequencies higher than the second formant. High correlation was
      shown between the perceptual ratings and the predicted values derived from
      stepwise regression analysis.

PMID- 10931271
TI  - Chewing ability and quality of life among the elderly residing in a rural
      community in Japan.
AB  - The present study statistically evaluates the relationship between chewing
      ability and quality of life (QOL) in elderly Japanese residents. We used a
      subjective evaluation and a mastication score determined by the food intake
      status to evaluate chewing ability. The PGC morale scale was used to evaluate the
      QOL level. The mastication score was significantly related to the QOL level in
      the subject group (P<0.05). The relationship between the subjective evaluation of
      chewing ability and the score on the PGC morale scale showed a similar tendency.
      In the section of the PGC morale scale that assesses agitation, attitude towards
      own aging, and lonely dissatisfaction, chewing ability was correlated with
      attitude toward own aging in particular (P<0.05). These results have suggested
      that the chewing ability is closely related to the QOL of the elderly residing in
      a rural community in Japan.

PMID- 10931272
TI  - Lewis antigens in Helicobacter pylori: biosynthesis and phase variation.
AB  - The lipopolysaccharides (LPS) of most Helicobacter pylori strains contain complex
      carbohydrates known as Lewis antigens that are structurally related to the human
      blood group antigens. Investigations on the genetic determinants involved in the
      biosynthesis of Lewis antigens have led to the identification of the
      fucosyltransferases of H. pylori, which have substrate specificities distinct
      from the mammalian fucosyltransferases. Compared with its human host, H. pylori
      utilizes a different pathway to synthesize the difucosylated Lewis antigens,
      Lewis y. and Lewis b. Unique features in the H. pylori fucosyltransferase genes,
      including homopolymeric tracts mediating slipped-strand mispairing and the
      elements regulating translational frameshifting, enable H. pylori to produce
      variable LPS epitopes on its surface. These new findings have provided us with a
      basis to further examine the roles of molecular mimicry and phase variation of H.
      pylori Lewis antigen expression in both persistent infection and pathogenesis of
      this important human gastric pathogen.

PMID- 10931273
TI  - Peptide deformylase as a target for new generation, broad spectrum antimicrobial
      agents.
AB  - Peptide deformylase was discovered 30 years ago, but as a result of its unusually
      unstable activity it was not fully characterized until very recently. The aim of
      this paper is to review the many recent data concerning this enzyme and to try to
      assess its potential as a target for future antimicrobial drugs.

PMID- 10931274
TI  - Identification of SopE2 from Salmonella typhimurium, a conserved guanine
      nucleotide exchange factor for Cdc42 of the host cell.
AB  - Salmonella typhimurium translocates effector proteins into host cells via the
      SPI1 type III secretion system to induce responses such as membrane ruffling and
      internalization by non-phagocytic cells. Activation of the host cellular
      RhoGTPase Cdc42 is thought to be a key event during internalization. The
      translocated Salmonella protein SopE is an activator for Cdc42. Because SopE is
      absent from most S. typhimurium strains it remains unclear whether all S.
      typhimurium strains rely on activation of Cdc42 to invade host cells. We have
      identified SopE2, a translocated effector protein common to all S. typhimurium
      strains. SopE2 is a guanine nucleotide exchange factor for Cdc42 and shows 69%
      sequence similarity to SopE. Analysis of S. typhimurium mutants demonstrated that
      SopE2 plays a role in recruitment of the actin-nucleating Arp2/3 complex to the
      membrane ruffles and in efficient host cell invasion. Transfection experiments
      showed that SopE2 is sufficient to activate host cellular Cdc42, to recruit the
      actin-nucleating Arp2/3 complex and to induce actin cytoskeletal rearrangements
      and internalization. In conclusion, as a result of SopE2 all S. typhimurium
      strains tested have the capacity to activate Cdc42 signalling inside host cells
      which is important to ensure efficient entry.

PMID- 10931275
TI  - Identification and localization of a methyl-accepting chemotaxis protein in
      Rhodobacter sphaeroides.
AB  - Genes coding for a classical membrane spanning chemoreceptor (mcpG) and a
      response regulator (cheY4) were identified in a region of Rhodobacter sphaeroides
      DNA unlinked to either of the two previously identified chemosensory operons.
      Immunogold electron microscopy had shown that the expression of chemoreceptors in
      R. sphaeroides varies with growth conditions. Using GFP fused to the newly
      identified McpG, we examined the targeting of this single methyl-accepting
      chemotaxis protein (MCP) under different growth conditions. The gene encoding the
      C-terminal McpG-GFP fusion was introduced by homologous recombination into the
      chromosome, replacing the wild-type gene. The resultant protein localized to the
      poles of the cell under aerobic, photoheterotrophic and anaerobic dark
      conditions, demonstrating that this MCP is expressed under all three growth
      conditions. More protein was always found at one pole than the other. The polar
      fluorescence increased during the cell cycle, with protein becoming evident at
      the second pole around the time of septation. At division, each daughter cell had
      a label at one pole, but the intensity of fluorescence was higher in the daughter
      cell containing the original labelled pole. McpG localization was not altered in
      a che Operon 1 deletion strain, lacking CheW1 and CheA1, but a che Operon 2
      deletion strain, lacking CheW2, CheW3 and CheA2, showed significantly reduced
      polar localization. This observation indicates that polar localization of McpG
      depends on Che proteins encoded by Operon 2, but not homologues encoded by Operon
      1.

PMID- 10931276
TI  - Study of chromosome rearrangements associated with the trpE26 mutation of
      Bacillus subtilis.
AB  - Chromosome rearrangements involved in the formation of merodiploid strains in the
      Bacillus subtilis 168-166 system were explained by postulating the existence of
      intrachromosomal homology regions. This working hypothesis was tested by
      analysing sequences and restriction patterns of the, as yet uncharacterized,
      junctions between chromosome segments undergoing rearrangements in parent, 168
      trpC2 and 166 trpE26, as well as in derived merodiploid strains. Identification,
      at the Ia/Ib chromosome junction of both parent strains, of a 1.3 kb segment
      nearly identical to a segment of prophage SPbeta established the existence of one
      of the postulated homology sequences. Inspection of relevant junctions revealed
      that a set of different homology regions, derived from prophage SPbeta, plays a
      key role in the formation of so-called trpE30, trpE30+, as well as of new class I
      merodiploids. Analysis of junctions involved in the transfer of the trpE26
      mutation, i.e. simultaneous translocation of chromosome segment C and rotation of
      the terminal relative to the origin moiety of the chromosome, did not confirm the
      presence of any sequence suitable for homologous recombination. We propose a
      model involving simultaneous introduction of four donor DNA molecules, each
      comprising a different relevant junction, and their pairing with the junction
      regions of the recipient chromosome. The resolution of this structure, resting on
      homologous recombination, would confer the donor chromosome structure to the
      recipient, achieving some kind of 'transstamping'. In addition, a rather regular
      pattern of inverse and direct short sequence repeats in regions flanking the
      breaking points could be correlated with the initial, X-ray-induced,
      rearrangement.

PMID- 10931277
TI  - Morphogenesis in Aspergillus nidulans requires Dopey (DopA), a member of a novel
      family of leucine zipper-like proteins conserved from yeast to humans.
AB  - DopA is the founding member of a novel protein family required for correct cell
      morphology and spatiotemporal organization of multicellular structures in the
      filamentous fungus Aspergillus nidulans. DopA homologues from Saccharomyces
      cerevisiae (Dop1), Candida albicans, Caenorhabditis elegans, Rattus norvegicus
      and Homo sapiens have been identified from genome sequencing projects. S.
      cerevisiae DOP1 is essential for viability and, like DopA, affects cellular
      morphogenesis. dopA encodes a large protein (207 kDa) containing several putative
      domains, including three leucine zipper-like domains. Strains with either the
      temperature-sensitive dopA1(ts) allele, which alters one of the leucine zippers,
      or the null deltadopA allele, had abnormal morphology of the vegetative hyphae,
      delayed and asynchronous initiation of asexual development, aberrant
      morphogenesis of the conidiophore and an early block in the sexual cycle. The
      expression patterns of key transcriptional regulators of the asexual and sexual
      cycle (brlA, abaA and steA) are altered in a deltadopA background, suggesting
      that DopA functions upstream in the developmental pathway. Double mutant analysis
      showed that dopA interacts genetically with constitutively active and inactive
      forms of A. nidulans Aras to modulate hyphal morphogenesis and asexual
      development.

PMID- 10931279
TI  - Global analysis of transcription kinetics during competence development in
      Streptococcus pneumoniae using high density DNA arrays.
AB  - The kinetics of global changes in transcription patterns during competence
      development in Streptococcus pneumoniae was analysed with high-density arrays.
      Four thousand three hundred and one clones of a S. pneumoniae library, covering
      almost the entire genome, were amplified by PCR and gridded at high density onto
      nylon membranes. Competence was induced by the addition of CSP (competence
      stimulating peptide) to S. pneumoniae cultures grown to the early exponential
      phase. RNA was extracted from samples at 5 min intervals (for a period of 30 min)
      after the addition of CSP. Radiolabelled cDNA was generated from isolated total
      RNA by random priming and the probes were hybridized to identical high density
      arrays. Genes whose transcription was induced or repressed during competence were
      identified. Most of the genes previously known to be competence induced were
      detected together with several novel genes that all displayed the characteristic
      transient kinetics of competence-induced genes. Among the newly identified genes
      many have suggested functions compatible with roles in genetic transformation.
      Some of them may represent new members of the early or late competence regulons
      showing competence specific consensus sequences in their promoter regions.
      Northern experiments and mutational analysis were used to confirm some of the
      results.

PMID- 10931278
TI  - Different alleles of the response regulator gene bldM arrest Streptomyces
      coelicolor development at distinct stages.
AB  - whiK was one of five new whi loci identified in a recent screen of NTG-induced
      whi mutants and was defined by three mutants, R273, R318 and R655. R273 and R318
      produce long, tightly coiled aerial hyphae with frequent septation. In contrast,
      R655 shows a more severe phenotype; it produces straight, undifferentiated aerial
      hyphae with very rare short chains of spores. Subcloning and sequencing showed
      that whiK encodes a member of the FixJ subfamily of response regulators, with a C
      terminal helix-turn-helix DNA-binding domain and an apparently typical N-terminal
      phosphorylation pocket. Unexpectedly, a constructed whiK null mutant failed to
      form aerial mycelium, showing that different alleles of this locus can arrest
      Streptomyces coelicolor development at very distinct stages. As a consequence of
      the null mutant phenotype, whiK was renamed bldM. The bldM null mutant fits into
      the extracellular signalling cascade proposed for S. coelicolor and is a member
      of the bldD extracellular complementation group. The three original NTG-induced
      mutations that defined the whiK/bldM locus each affected the putative
      phosphorylation pocket. The mutations in R273 and in R318 were the same,
      replacing a highly conserved glycine (G-62) with aspartate. The more severe
      mutant, R655, carried a C-7Y substitution adjacent to the highly conserved DD
      motif at positions 8-9. However, although bldM has all the highly conserved
      residues associated with the phosphorylation pocket of conventional response
      regulators, aspartate-54, the putative site of phosphorylation, is not required
      for bldM function. Constructed mutant alleles carrying either D-54N or D-54A
      substitutions complemented the bldM null mutant in single copy in trans, and
      strains carrying the D-54N or the D-54A substitution at the native chromosomal
      bldM locus sporulated normally. bldM was not phosphorylated in vitro with either
      of the small-molecule phosphodonors acetyl phosphate or carbamoyl phosphate under
      conditions in which a control response regulator protein, NtrC, was labelled
      efficiently.

PMID- 10931280
TI  - Upstream nucleosomes and Rgr1p are required for nucleosomal repression of
      transcription.
AB  - The mechanisms of transcription repression and derepression in vivo are not fully
      understood. We have obtained evidence that begins to clarify the minimum
      requirements for counteracting nucleosomal repression in vivo. Location of the
      TATA element near the nucleosome dyad does not block RNA polymerase II
      transcription in vivo if there is a nucleosome-free region located immediately
      upstream. However, location of the TATA element similarly within the nucleosome
      does block transcription if the region upstream of it is nucleosome bound.
      Histone H4 depletion derepresses transcription in the latter case, supporting the
      idea that the nucleosomes are responsible for the repression. These results raise
      the intriguing possibility that the minimum requirement for derepression of
      transcription in vivo is a nucleosome-free region upstream of the core promoter.
      Importantly, we find that a C-terminal deletion in RGR1, a component of the
      mediator/holoenzyme complex and a global repressor, can also derepress
      transcription.

PMID- 10931281
TI  - Generation of a mature streptococcal cysteine proteinase is dependent on cell
      wall-anchored M1 protein.
AB  - In the present study, we have generated a mutant strain of Streptococcus
      pyogenes, MC25, which lacks M protein on its surface, and we demonstrate that
      this strain is unable to generate a mature 28 kDa cysteine proteinase.
      Furthermore, we show that S. pyogenes bacteria of M1 serotype are dependent on
      cell wall-anchored M protein to cleave the secreted zymogen into a mature
      cysteine proteinase. We also show that MC25 secretes a 40 kDa zymogen, having a
      conformation different from that secreted by wild-type bacteria. We provide data
      showing that the cleavage site is not blocked but, presumably, the active site
      is. This suggests that M protein, when anchored to the cell wall, is involved in
      the unfolding of the zymogen and generation of a mature cysteine proteinase that
      can be activated under reducing conditions. Our data add new aspects to the
      interaction between two important virulence factors of S. pyogenes, the
      streptococcal cysteine proteinase and M protein.

PMID- 10931282
TI  - The Escherichia coli SeqA protein binds specifically and co-operatively to two
      sites in hemimethylated and fully methylated oriC.
AB  - The Escherichia coli SeqA protein has been found to affect initiation of
      replication negatively, both in vivo and in vitro. The mechanism of inhibition
      is, however, not known. SeqA has been suggested to affect the formation and
      activity of the initiation complex at oriC, either by binding to DNA or by
      interacting with the DnaA protein. We have investigated the binding of SeqA to
      oriC by electron microscopy and found that SeqA binds specifically to two sites
      in oriC, one on each side of the DnaA binding site R1. Specific binding was found
      for fully and hemimethylated but not unmethylated oriC in good agreement with
      earlier mobility shift studies. The affinity of SeqA for hemi-methylated oriC was
      higher than for fully methylated oriC. The binding was in both cases strongly
      cooperative. We suggest that SeqA binds to two nucleation sites in oriC, and by
      the aid of protein-protein interaction spreads to adjacent regions in the same
      oriC as well as recruiting additional oriC molecules and/or complexes into larger
      aggregates.

PMID- 10931283
TI  - Functional specificity of the replication fork-arrest complexes of Bacillus
      subtilis and Escherichia coli: significant specificity for Tus-Ter functioning in
      E. coli.
AB  - The Escherichia coli replication terminator TerB was inserted in its two
      alternate orientations into a Bacillus subtilis fork-arrest assay plasmid. After
      transferring these new plasmids into B. subtilis, which could overproduce the E.
      coli terminator protein Tus, it was shown that the E. coli Tus-TerB complex could
      cause polar replication fork arrest, albeit at a very low level, in B. subtilis.
      A new B. subtilis-E. coli shuttle plasmid was designed to allow the insertion of
      either the Terl (B. subtilis) or TerB (E. coli) terminator at the same site and
      in the active orientation in relation to the approaching replication fork
      generated in either organism. Fork-arrest assays for both terminator-containing
      plasmids replicating in both organisms which also produced saturating levels of
      either the B. subtilis terminator protein (RTP) or Tus were performed. The
      efficiency of the Tus-TerB complex in causing fork arrest was much higher in E.
      coli than in B. subtilis. The efficiency of the B. subtilis RTP-Terl complex was
      higher in B. subtilis than in E. coli, but the effect was significantly less.
      Evidently a specificity feature in E. coli operates to enhance appreciably the
      fork-arrest efficiency of a Tus-Ter complex. The specificity effect is of less
      significance for an RTP-Ter complex functioning in B. subtilis.

PMID- 10931284
TI  - Proteolysis of SpolVB is a critical determinant in signalling of Pro-sigmaK
      processing in Bacillus subtilis.
AB  - SpoIVB is essential for intercompartmental signalling in the sigma(K)-checkpoint
      of Bacillus subtilis. SpoIVB is synthesized in the spore chamber and is the
      signal which activates proteolytic processing of pro-sigma(K) to its mature and
      active form sigma(K). We show here that SpoIVB is a serine peptidase of the SA
      clan. Expression of SpoIVB in Escherichia coli has shown that SpoIVB is able to
      self-cleave into at least three discrete products, and in vitro studies have
      shown cleavage in trans. Autoproteolysis of SpoIVB is tightly linked to the
      initiation of the two developmental functions of this protein, signalling of pro
      sigma(K) processing and a yet, uncharacterized, second function which is
      essential for the formation of heat-resistant spores. In B. subtilis, SpoIVB is
      synthesized as a zymogen and is subject to two levels of proteolysis. First,
      autoproteolysis generating intermediate products, at least one of which is
      proposed to be the active form, followed by processing by one or more enzymes to
      smaller species. This could provide a mechanism for switching off the active
      SpoIVB intermediate(s) and suggests a similarity to other proteolytic cascades
      such as those found in blood coagulation.

PMID- 10931285
TI  - FtsZ ring formation without subsequent cell division after replication runout in
      Escherichia coli.
AB  - In this report, we have investigated cell division after inhibition of initiation
      of chromosome replication in Escherichia coli. In a culture grown to the
      stationary phase, cells containing more than one chromosome were able to divide
      some time after restart of growth, under conditions not allowing initiation of
      chromosome replication. This shows that there is no requirement for cell division
      to take place within a certain time after initiation of chromosome replication.
      Continued growth without initiation of replication resulted in filamented cells
      that generally did not have any constrictions. Interestingly, FtsZ rings were
      formed in a majority of these cells as they reached a certain cell length. These
      rings appeared and were maintained for some time at the cell quarter positions on
      both sides of the centrally localized nucleoid. These results confirm previous
      findings that cell division sites are formed independently of chromosome
      replication and indicate that FtsZ ring assembly is dependent on cell size rather
      than on the capacity of the cell to divide. Disruption of the mukB gene caused a
      significant increase in the region occupied by DNA after the replication runout,
      consistent with a role of MukB in chromosome condensation. The aberrant nucleoid
      structure was accompanied by a shift in FtsZ ring positioning, indicating an
      effect of the nucleoid on the positioning of the FtsZ ring. A narrow cell length
      interval was found, under and over which primarily central and non-central FtsZ
      rings, respectively, were observed. This finding correlates well with the
      previously observed oscillatory movement of MinC and MinD in short and long
      cells.

PMID- 10931287
TI  - Signature-tagged and directed mutagenesis identify PABA synthetase as essential
      for Aspergillus fumigatus pathogenicity.
AB  - Signature-tagged mutagenesis (STM) is a method that has been used to screen for
      genes required for in vivo survival of pathogenic bacteria, but has not been used
      to investigate a eukaryotic pathogen in an animal model of disease. We have
      adapted STM to identify genes required for in vivo growth of the opportunistic
      fungal pathogen Aspergillus fumigatus. Using a mouse model of invasive pulmonary
      aspergillosis, we have isolated several mutant strains with defects in their
      ability to replicate in vivo. One strain unable to cause lethal infection was
      further characterized and found to have an insertion into the promoter of a gene
      (pabaA) encoding para-aminobenzoic acid synthetase, an enzyme catalyzing a late
      step in the biosynthesis of folate. The complete inability of this strain, and
      other pabaA- strains constructed in this study by targeted gene deletion, to
      cause lethal infection in mice confirms the importance of the folate synthesis
      pathway for in vivo survival of this pathogen. The successful application of STM
      to A. fumigatus demonstrates that in vivo genetic analysis of eukaryotic
      pathogens is feasible and could result in the identification of potential
      targets, such as para-aminobenzoic acid synthetase, for novel antifungal
      therapies.

PMID- 10931286
TI  - ClpB and HtpG facilitate de novo protein folding in stressed Escherichia coli
      cells.
AB  - DnaK-DnaJ-GrpE and GroEL-GroES are the best-characterized molecular chaperone
      systems in the cytoplasm of Escherichia coli. A number of additional proteins,
      including ClpA, ClpB, HtpG and IbpA/B, act as molecular chaperones in vitro, but
      their function in cellular protein folding remains unclear. Here, we examine how
      these chaperones influence the folding of newly synthesized recombinant proteins
      under heat-shock conditions. We show that the absence of either CIpB or HtpG at
      42 degrees C leads to increased aggregation of preS2-beta-galactosidase, a fusion
      protein whose folding depends on DnaK-DnaJ-GrpE, but not GroEL-GroES. However,
      only the deltaclpB mutation is deleterious to the folding of homodimeric Rubisco
      and cMBP, two proteins requiring the GroEL-GroES chaperonins to reach a proper
      conformation. Null mutations in clpA or the ibpAB operon do not affect the
      folding of these model substrates. Overexpression of ClpB, HtpG, IbpA/B or ClpA
      does not suppress inclusion body formation by the aggregation-prone protein preS2
      S'-beta-galactosidase in wild-type cells or alleviate recombinant protein
      misfolding in dnaJ259, grpE280 or groES30 mutants. By contrast, higher levels of
      DnaK-DnaJ, but not GroEL-GroES, restore efficient folding in deltaclpB cells.
      These results indicate that ClpB, and to a lesser extent HtpG, participate in de
      novo protein folding in mildly stressed E. coli cells, presumably by expanding
      the ability of the DnaK-DnaJ-GrpE team to interact with newly synthesized
      polypeptides.

PMID- 10931288
TI  - The control of intracellular glycerol in Saccharomyces cerevisiae influences
      osmotic stress response and resistance to increased temperature.
AB  - Glycerol has been demonstrated to serve as the major osmolyte of Saccharomyces
      cerevisiae. Consistently, mutant strains gpd1gpd2 and gpp1gpp2, which are devoid
      of the main glycerol biosynthesis pathway, have been shown to be osmosensitive.
      In addition, the primary hyperosmotic stress response is affected in these
      strains. Hog1p phosphorylation turned out to be prolonged and osmostress-induced
      gene expression is delayed compared with the kinetics observed in wild-type
      cells. A hog1 deletion strain was previously found to contain lower internal
      glycerol and therefore displays an osmosensitive phenotype. Here, we show that
      the osmosensitivity of hog1 is suppressed by growth at 37 degrees C. We reasoned
      that this temperature-remedial osmoresistance might be caused by a higher
      intracellular glycerol level at the elevated temperature. This hypothesis was
      confirmed by measurement of the glycerol concentration, which was shown to be
      similar for wild type and hog1 cells only at elevated growth temperatures. In
      agreement with this finding, hog1 cells containing an fps1 allele, encoding a
      constitutively open glycerol channel, have lost their temperature-remedial
      osmoresistance. Furthermore, gpd1gpd2 and gpp1gpp2 strains were found to be
      temperature sensitive. The growth defect of these strains could be suppressed by
      adding external glycerol. In conclusion, the ability to control glycerol levels
      influences proper osmostress-induced signalling and the cellular potential to
      grow at elevated temperatures. These data point to an important, as yet
      unidentified, role of glycerol in cellular functioning.

PMID- 10931289
TI  - Rns, a virulence regulator within the AraC family, requires binding sites
      upstream and downstream of its own promoter to function as an activator.
AB  - Strains of enterotoxigenic Escherichia coli that express CS1 and CS2 pili require
      the transcriptional activator Rns, a member of the AraC family, for the
      expression of the pilin genes. Rns is also an activator of its own expression.
      However, the arrangement of its binding sites near its own promoter is unusual
      for a prokaryotic activator. Most activators have at least one binding site 30-80
      nucleotides upstream of the transcription start site, but Rns has a single
      upstream binding site centred at -227. Rns also has two binding sites downstream
      of the transcription start site centred at +43 and +82, a region generally
      thought to be reserved for repressors. In vitro, the binding of a MBP::Rns fusion
      protein to each of these sites facilitates the binding of RNA polymerase to the
      rns promoter and the formation of an open complex. In vivo, the upstream binding
      site and one downstream site are required for Rns-dependent activation of its
      promoter despite the atypical location of these binding sites for an activator.
      This suggests that Rns may represent a new class of prokaryotic activators.

PMID- 10931290
TI  - Evidence for the genetic interaction between the actin-binding protein Vrp1 and
      the RhoGAP Rgd1 mediated through Rho3p and Rho4p in Saccharomyces cerevisiae.
AB  - The non-essential RGD1 gene from Saccharomyces cerevisiae encodes a protein that
      has been characterized in vitro as a Rho GTPase activating protein (RhoGAP) for
      the Rho3 and Rho4 proteins. Rgd1p, which displays a conserved FCH-coiled coil-Rho
      GAP domain organization, showed a patch-like distribution in the cell, including
      a localization in growing buds. Using a genetic screen, we found that rgd1delta
      and vrp1alpha mutations exhibited a synthetic lethality, thus revealing an
      interaction between these genes. The VRP1 product is an actin and myosin
      interacting protein involved in polarized growth. Using mutant forms of both Rho3
      and Rho4 proteins, we provide evidence for the involvement of these two GTPases
      in RGD1-VRP1 co-lethality. In addition, these results strongly argue in favour of
      Rho3p and Rho4p being the targets of Rgd1p RhoGAP activity in vivo. Genetic
      relationships between either VRP1 or RGD1 and actin cytoskeleton-linked genes
      were also studied. These and other well-established data support the idea that
      Vrp1, Las17, Rvs167 proteins belong to the same complex. This protein structure
      might act with myosins in various actin cytoskeleton-based activities, in co
      operation with a Rho3p/Rho4p signalling pathway that is negatively regulated by
      Rgd1p GAP activity.

PMID- 10931291
TI  - BofC negatively regulates SpoIVB-mediated signalling in the Bacillus subtilis
      sigmaK-checkpoint.
AB  - The BofC protein acts negatively on intercompartmental signalling of pro-sigma(K)
      processing in the sigma(K)-checkpoint of Bacillus subtilis. Signalling is brought
      about by the SpoIVB protein, which is synthesized in the forespore and initiates
      proteolytic processing of pro-sigmaK to its mature and active form in the opposed
      mother cell chamber of the developing cell. We have shown here that BofC, like
      SpoIVB, is secreted across the inner forespore membrane and, from the analysis of
      a bofC deletion and insertion mutant, is likely to interact with SpoIVB. In the
      absence of BofC, the amount of SpoIVB found in sporulating cells is substantially
      reduced, although SpoIVB is still able to activate proteolysis of pro-sigma(K).
      Conversely, in the absence of SpoIVB, the levels of BofC accumulate suggesting
      that the fate of each molecule is dependent upon their mutual interaction. Our
      results suggest that BofC could maintain SpoIVB in a stable but inactive form.
      Supporting this, we have shown that overproduction of BofC inhibits SpoIVB
      autoproteolysis and leads to a delay in proteolytic cleavage of pro-sigma(K).
      Based on our work here, we have proposed a model for BofC's functional role in
      intercompartmental signalling.

PMID- 10931292
TI  - A role for lipopolysaccharide in turkey tracheal colonization by Bordetella avium
      as demonstrated in vivo and in vitro.
AB  - We isolated two insertion mutants of Bordetella avium that exhibited a peculiar
      clumped-growth phenotype and found them to be attenuated in turkey tracheal
      colonization. The mutants contained transposon insertions in homologues of the
      wlbA and wlbL genes of Bordetella pertussis. The wlb genetic locus of B.
      pertussis has been previously described as containing 12 genes involved in
      lipopolysaccharide (LPS) biosynthesis. Polyacrylamide gel analysis of LPS from B.
      avium wlbA and wlbL insertion mutants confirmed an alteration in the LPS profile.
      Subsequent cloning and complementation of the wlbA and wlbL mutants in trans with
      a recombinant plasmid containing the homologous wlb locus from B. avium
      eliminated the clumped-growth phenotype and restored the LPS profile to that of
      wild-type B. avium. Also, a parental level of tracheal colonization was restored
      to both mutants by the recombinant plasmid. Interestingly, complementation of the
      wlbA and wlbL mutants with a recombinant plasmid containing the heterologous wlb
      locus from B. pertussis, B. bronchiseptica, or Bordetella parapertussis
      eliminated the clumped-growth phenotype and resulted in a change in the LPS
      profile, although not to that of wild-type B. avium. The mutants also acquired
      resistance to a newly identified B. avium-specific bacteriophage, Ba1.
      Complementation of both wlbA and wlbL mutants with the homologous wlb locus of B.
      avium, but not the heterologous B. pertussis locus, restored sensitivity to Ba1.
      Complementation of the wlbL mutant, but not the wlbA mutant, with the
      heterologous wlb locus of Bordetella bronchiseptica or B. parapertussis restored
      partial sensitivity to Ba1. Comparisons of the LPS profile and phage sensitivity
      of the mutants upon complementation by wlb loci from the heterologous species and
      by B. avium suggested that phage sensitivity required the presence of O-antigen.
      At the mechanistic level, both mutants showed a dramatic decrease in serum
      resistance and a decrease in binding to turkey tracheal rings in vitro. In the
      case of serum resistance, complementation of both mutants with the homologous wlb
      locus of B. avium restored serum resistance to wild-type levels. However, in the
      case of epithelial cell binding, only complementation of the wlbA mutant
      completely restored binding to wild-type levels (binding was only partially
      restored in the wlbL mutant). This is the first characterization of LPS mutants
      of B. avium at the genetic level and the first report of virulence changes by
      both in vivo and in vitro measurements.

PMID- 10931293
TI  - A chromosomally encoded type III secretion pathway in Yersinia enterocolitica is
      important in virulence.
AB  - Numerous Gram-negative bacteria use a type III, or contact dependent, secretion
      system to deliver proteins into the cytosol of host cells. All of these systems
      identified to date have been shown to have a role in pathogenesis. We have
      identified 13 genes on the Yersinia enterocolitica chromosome that encode a type
      III secretion apparatus plus two associated putative regulatory genes. In order
      to determine the function of this chromosomally-encoded secretion apparatus, we
      created an in frame deletion of a gene that has homology to the hypothesized
      inner membrane pore, ysaV. The ysaV mutant strain failed to secrete eight
      proteins, called Ysps, normally secreted by the parental strain when grown at 28
      degrees C in Luria-Bertani (LB) broth supplemented with 0.4 M NaCl. Disruption of
      the ysaV gene had no effect on motility or phospholipase activity, suggesting
      this chromosomally encoded type III secretion pathway is distinct from the
      flagella secretion pathway of Y. enterocolitica. Deletion of the ysaV gene in a
      virulence plasmid positive strain had no effect on in vitro secretion of Yops by
      the plasmid-encoded type III secretion apparatus. Secretion of the Ysps was
      unaffected by the presence or absence of the virulence plasmid, suggesting the
      chromosomally encoded and plasmid-encoded type III secretion pathways act
      independently. Y. enterocolitica thus has three type III secretion pathways that
      appear to act independently. The ysaV mutant strain was somewhat attenuated in
      virulence compared with the wild type in the mouse oral model of infection (an
      approximately 0.9 log difference in LD50). The ysaV mutant strain was nearly as
      virulent as the wild type when inoculated intraperitoneally in the mouse model. A
      ysaV probe hybridized to sequences in other Yersinia spp. and homologues were
      found in the incomplete Y. pestis genome sequence, indicating a possible role for
      this system throughout the genus.

PMID- 10931294
TI  - A chimeric ribozyme in clostridium difficile combines features of group I introns
      and insertion elements.
AB  - CdlSt1, a DNA insertion of 1975 bp, was identified within tcdA-C34, the
      enterotoxin gene of the Clostridium difficile isolate C34. Located in the
      catalytic domain A1-C34, Cd/St1 combines features of two genetic elements. Within
      the first 434 nt structures characteristic for group I introns were found;
      encoding the two transposase-like proteins tlpA and tlpB nucleotides 435-1975
      represent the remainder of a IS605-like insertion element. We show that the
      entire CdlSt1 is accurately spliced from tcdA-C34 primary transcripts and that
      purified TcdA-C34 toxin is of regular size and catalytic activity. A search for
      CdlSt1-related sequences demonstrates that the element is widespread in
      toxinogenic and non-toxinogenic C. difficile strains, indicating the mobility of
      CdlSt1. In strain C34, we characterize 10 CdlSt1 variants; all are highly
      homologous to CdlSt1 (> 93% identity), integrated in bacterial open reading
      frames (ORFs), show the typical composite structure of CdlSt1 and are precisely
      spliced from their primary transcripts. CdlSt1-like chimeric ribozymes appear to
      combine the invasiveness of an insertion element with the splicing ability of a
      group I intron, rendering transposition harmless for the interrupted gene.

PMID- 10931295
TI  - Redox regulation of AMP synthesis in yeast: a role of the Bas1p and Bas2p
      transcription factors.
AB  - Expression of yeast AMP synthesis genes (ADE genes) was severely affected when
      cells were grown under oxidative stress conditions. To get an insight into the
      molecular mechanisms of this new transcriptional regulation, the role of the
      Bas1p and Bas2p transcription factors, known to activate expression of the ADE
      genes, was investigated. In vitro, DNA-binding of Bas1p was sensitive to
      oxidation. However, this sensitivity could not account for the regulation of the
      ADE genes because we showed, using a BAS1-VP16 chimera, that Bas1p DNA-binding
      activity was not sensitive to oxidation in vivo. Consistently, a triple cysteine
      mutant of Bas1p (fully resistant to oxidation in vitro) was unable to restore
      transcription of the ADE genes under oxidative conditions. We then investigated
      the possibility that Bas2p could be the oxidative stress responsive factor.
      Interestingly, transcription of the PHO5 gene, which is dependent on Bas2p but
      not on Bas1p, was found to be severely impaired by oxidative stress.
      Nevertheless, a Bas2p cysteine-free mutant was not sufficient to confer
      resistance to oxidative stress. Finally, we found that a Bas1p-Bas2p fusion
      protein restored ADE gene expression under oxidative conditions, thus suggesting
      that redox sensitivity of ADE gene expression could be due to an impairment of
      Bas1p/Bas2p interaction. This hypothesis was further substantiated in a two
      hybrid experiment showing that Bas1p/Bas2p interaction is affected by oxidative
      stress.

PMID- 10931296
TI  - Transcriptional and post-transcriptional control of polynucleotide phosphorylase
      during cold acclimation in Escherichia coli.
AB  - Polynucleotide phosphorylase (PNPase, polyribonucleotide nucleotidyltransferase,
      EC 2.7.7.8) is one of the cold shock-induced proteins in Escherichia coli and
      pnp, the gene encoding it, is essential for growth at low temperatures. We have
      analysed the expression of pnp upon cold shock and found a dramatic transient
      variation of pnp transcription profile: within the first hour after temperature
      downshift the amount of pnp transcripts detectable by Northern blotting increased
      more than 10-fold and new mRNA species that cover pnp and the downstream region,
      including the cold shock gene deaD, appeared; 2 h after temperature downshift the
      transcription profile reverted to a preshift-like pattern in a PNPase-independent
      manner. The higher amount of pnp transcripts appeared to be mainly due to an
      increased stability of the RNAs. The abundance of pnp transcripts was not
      paralleled by comparable variation of the protein: PNPase steadily increased
      about twofold during the first 3 h at low temperature, as determined both by
      Western blotting and enzymatic activity assay, suggesting that PNPase, unlike
      other known cold shock proteins, is not efficiently translated in the acclimation
      phase. In experiments aimed at assessing the role of PNPase in autogenous control
      during cold shock, we detected a Rho-dependent termination site within pnp. In
      the cold acclimation phase, termination at this site depended upon the presence
      of PNPase, suggesting that during cold shock pnp is autogenously regulated at the
      level of transcription elongation.

PMID- 10931297
TI  - Clinical and environmental isolates of Burkholderia cepacia exhibit differential
      cytotoxicity towards macrophages and mast cells.
AB  - Burkholderia cepacia is an emerging opportunistic pathogen that causes fatal
      infections in patients suffering from cystic fibrosis (CF) and chronic
      granulomatous disease. Various environmental isolates of B. cepacia are, however,
      capable of degrading environmental pollutants, such as trichloroethylene, 2,4,5
      trichlorophenoxyacetic acid (2,4,5-T), etc., and are also highly effective in
      controlling plant diseases caused by nematodes and fungi. Such strains have
      therefore been proposed for environmental release to clean up toxic dump sites or
      as biopesticides. Various efforts to distinguish between clinical and
      environmental isolates of B. cepacia with regard to their virulence
      characteristics have produced ambiguous results, suggesting that newer methods
      are needed to test for the presence or absence of pathogenic potential in B.
      cepacia strains proposed for environmental release. We now report that several
      clinical strains of B. cepacia secrete cytotoxic factors that allow macrophage
      and mast cell death in the presence of external ATP. Several environmental
      strains had reduced activity in this regard. We also demonstrate that, while all
      the strains secrete enzymes that have nucleoside diphosphate kinase (Ndk),
      adenylate kinase (Ak) and 5'-nucleotidase activity, the level of secretion of the
      5'-nucleotidase (and/or ATPase/phosphatase) appears to be lower in the
      environmental strains than in the clinical strains. The secretion of these
      enzymes is specifically activated in the presence of eukaryotic proteins such as
      alpha2-macroglobulin. As macrophage-or mast cell surface-associated P2Z receptors
      promote their cell death in the presence of mM concentrations of ATP, and as the
      secreted ATP-using enzymes generate various phosphorylated or non-phosphorylated
      adenine nucleotides that may even be better agonists than ATP in activating the
      P2Z receptors or may act through the activation of additional purinergic
      receptors, such enzymes may play an important role in allowing B. cepacia to
      evade host defence.

PMID- 10931298
TI  - The universal stress protein A of Escherichia coli is required for resistance to
      DNA damaging agents and is regulated by a RecA/FtsK-dependent regulatory pathway.
AB  - The link between cell division defects and the induction of the universal stress
      response is demonstrated to operate via the RecA regulator of the SOS response.
      An insertion in the cell division gene ftsK upregulates uspA in a recA-dependent
      manner. Unlike true SOS response genes, this upregulation only occurs in growth
      arrested cells and is LexA independent. Thus, besides ppGpp-dependent starvation
      signals, DNA aberrations transduce RecA-dependent signals to the uspA promoter,
      which only affect the promoter during stasis. Further, we show that ftsK itself,
      like uspA, is induced in stationary phase and that this induction requires the
      stringent control modulon rather than activated RecA. Thus, ftsK, like uspA, is
      regulated by at least two global regulators: ppGpp of the stringent control
      network and RecA of the SOS modulon. We suggest that UspA is a new bona fide
      member of the RecA-dependent DNA protection and repair system, as mutants lacking
      functional UspA were found to be sensitive to UV irradiation and mitomycin C
      exposure. Moreover, the UV sensitivity of uspA mutants is enhanced in an additive
      manner by the ftsK1 mutation.

PMID- 10931299
TI  - High rates of phase variation in Campylobacter jejuni?

PMID- 10931301
TI  - Assembly of aryl-capped siderophores by modular peptide synthetases and
      polyketide synthases.
AB  - Bacterial siderophores assist pathogens in iron acquisition inside their hosts.
      They are often essential for achieving a successful infection, and their
      biosynthesis represents an attractive antibiotic target. Recently, several
      siderophore biosynthetic loci have been identified, and in vitro studies have
      advanced our knowledge of the biosynthesis of aryl-capped peptide and peptide
      polyketide siderophores from Mycobacterium spp., Pseudomonas spp., Yersinia spp.
      and other bacteria. These studies also provided insights into the assembly of
      related siderophores and many secondary metabolites of medical relevance.
      Assembly of aryl-capped peptide and peptide-polyketide siderophores involves non
      ribosomal peptide synthetase, polyketide synthase and non-ribosomal-peptide
      polyketide hybrid subunits. Analysis of these subunits suggests that their
      domains and modules are functionally and structurally independent. It appears
      that nature has selected a set of functional domains and modules that can be
      rearranged in different order and combinations to biosynthesize different
      products. Although much remains to be learned about modular synthetases and
      synthases, it is already possible to conceive strategies to engineer these
      enzymes to generate novel products.

PMID- 10931302
TI  - Non-typeable Haemophilus influenzae adhere to and invade human bronchial
      epithelial cells via an interaction of lipooligosaccharide with the PAF receptor.
AB  - Adherence and invasion are thought to be key events in the pathogenesis of non
      typeable Haemophilus influenzae (NTHi). The role of NTHi lipooligosaccharide
      (LOS) in adherence was examined using an LOS-coated polystyrene bead adherence
      assay. Beads coated with NTHi 2019 LOS adhered significantly more to 16HBE14
      human bronchial epithelial cells than beads coated with truncated LOS isolated
      from an NTHi 2019 pgmB:ermr mutant (P = 0.037). Adherence was inhibited by
      preincubation of cell monolayers with NTHi 2019 LOS (P = 0.0009), but not by
      preincubation with NTHi 2019 pgmB:ermr LOS. Competitive inhibition studies with a
      panel of compounds containing structures found within NTHi LOS suggested that a
      phosphorylcholine (ChoP) moiety was involved in adherence. Further experiments
      revealed that mutations affecting the oligosaccharide region of LOS or the
      incorporation of ChoP therein caused significant decreases in the adherence to
      and invasion of bronchial cells by NTHi 2019 (P < 0.01). Analysis of infected
      monolayers by confocal microscopy showed that ChoP+ NTHi bacilli co-localized
      with the PAF receptor. Pretreatment of bronchial cells with a PAF receptor
      antagonist inhibited invasion by NTHi 2109 and two other NTHi strains expressing
      ChoP+ LOS glycoforms exhibiting high reactivity with an anti-ChoP antibody on
      colony immunoblots. These data suggest that a particular subset of ChoP+ LOS
      glycoforms could mediate NTHi invasion of bronchial cells by means of interaction
      with the PAF receptor.

PMID- 10931303
TI  - c-Jun and RACK1 homologues regulate a control point for sexual development in
      Aspergillus nidulans.
AB  - Amino acid limitation results in impaired sexual fruit body formation in
      filamentous fungi such as Aspergillus nidulans. The starvation signal is
      perceived by the cross-pathway regulatory network controlling the biosynthesis of
      translational precursors and results in increased expression of a transcriptional
      activator encoded by a c-Jun homologue. In the presence of amino acids, the gene
      product of the mammalian RACK1 homologue cpcB is required to repress the network.
      Growth under amino acid starvation conditions permits the initiation of the
      sexual developmental programme of the fungus, but blocks fruit body formation
      before completion of meiosis. Accordingly, arrest at this defined control point
      results in microcleistothecia filled with hyphae. Addition of amino acids results
      in release of the block and completion of development to mature ascospores. The
      same developmental block is induced by either overexpression of c-Jun homologues
      or deletion of the RACK1 homologue cpcB of A. nidulans in the presence of amino
      acids. Therefore, the amino acid starvation signal regulates sexual development
      through the network that also controls the amino acid biosynthetic genes.
      Expression of the RACK1 gene suppresses the block in development caused by a
      deletion of cpcB. These data illuminate a connection between metabolism and
      sexual development in filamentous fungi.

PMID- 10931304
TI  - Trehalose is required for conformational repair of heat-denatured proteins in the
      yeast endoplasmic reticulum but not for maintenance of membrane traffic functions
      after severe heat stress.
AB  - Saccharomyces cerevisiae cells grown at physiological temperature 24 degrees C
      require preconditioning at 37 degrees C to acquire tolerance towards brief
      exposure to 48-50 degrees C. During preconditioning, the cytosolic trehalose
      content increases remarkably and in the absence of trehalose synthesis yeast
      cannot acquire thermotolerance. It has been speculated that trehalose protects
      proteins and membranes under environmental stress conditions, but recently it was
      shown to assist the Hsp104 chaperone in refolding of heat-damaged proteins in the
      yeast cytosol. We have demonstrated that heat-denatured proteins residing in the
      endoplasmic reticulum (ER) also can be refolded once the cells are returned to
      physiological temperature. Unexpectedly, not only ER chaperones but also the
      cytosolic Hsp104 chaperone is required for conformational repair events in the ER
      lumen. Here we show that trehalose facilitates refolding of glycoproteins in the
      ER after severe heat stress. In the absence of Tps1p, a subunit of trehalose
      synthase, refolding of heat-damaged glycoproteins to bioactive and secretion
      competent forms failed or was retarded. In contrast, membrane traffic operated
      many hours after severe heat stress even in the absence of the TPS1 gene,
      demonstrating that trehalose had no role in thermoprotection of membranes engaged
      in vesicular traffic. However, cytosolic proteins were aggregated and protein
      synthesis abolished, resulting finally in cell death.

PMID- 10931305
TI  - Identification of a target gene for the bE-bW homeodomain protein complex in
      Ustilago maydis.
AB  - In the phytopathogenic fungus Ustilago maydis, sexual and pathogenic development
      are controlled by the multiallelic b mating type locus. The b locus encodes a
      pair of unrelated homeodomain proteins termed bE and bW that form a heterodimeric
      complex when both proteins originate from different alleles. The heterodimer is
      presumed to be the central regulator for pathogenicity genes. Here, we show that
      a translational fusion protein comprising specific domains of bE1 and bW2 remains
      biologically active and binds to a sequence motif in the promoter of lga2, a gene
      located in the a mating type locus. This b binding sequence 1 (bbs1) is also
      recognized by the native bE1-bW2 heterodimer in vivo and mediates the b-dependent
      regulation of the lga2 gene. Our data demonstrate that the bE-bW heterodimer can
      act as a positive transcriptional regulator.

PMID- 10931306
TI  - Temperature-regulated efflux pump/potassium antiporter system mediates resistance
      to cationic antimicrobial peptides in Yersinia.
AB  - Most bacterial pathogens are resistant to cationic antimicrobial peptides (CAMPs)
      that are key components of the innate immunity of both vertebrates and
      invertebrates. In Gram-negative bacteria, the known CAMPs resistance mechanisms
      involve outer membrane (OM) modifications and specifically those in the
      lipopolysaccharide (LPS) molecule. Here we report, the characterization of a
      novel CAMPs resistance mechanism present in Yersinia that is dependent on an
      efflux pump/potassium antiporter system formed by the RosA and RosB proteins. The
      RosA/RosB system is activated by a temperature shift to 37 degrees C, but is also
      induced by the presence of the CAMPs, such as polymyxin B. This is the first
      report of a CAMPs resistance system that is induced by the presence of CAMPs. It
      is proposed that the RosA/RosB system protects the bacteria by both acidifying
      the cytoplasm to prevent the CAMPs action and pumping the CAMPs out of the cell.

PMID- 10931307
TI  - The regulatory locus cinRI in Rhizobium leguminosarum controls a network of
      quorum-sensing loci.
AB  - N-(3-hydroxy-7-cis-tetradecenoyl)-L-homoserine lactone (3OH, C14:1-HSL) is a
      quorum-sensing signalling molecule produced by Rhizobium leguminosarum. It is
      unusual in that it inhibits the growth of several strains of R. leguminosarum and
      was previously known as 'small bacteriocin'. The cinRI locus responsible for the
      production of 3OH,C14:1-HSL has been characterized; it is predicted to be on the
      chromosome, based on DNA hybridization. The cinR and cinI genes are in different
      transcriptional units, separated by a predicted transcription terminator. CinR
      regulates cinI expression to a very high level in a cell-density dependent
      manner, and cinI expression is positively autoregulated by 3OH,C14:1-HSL, the
      only identified N-acyl homoserine lactone (AHL) produced by CinI. No other AHLs
      were identified that strongly induced cinI expression. Mutation of cinI or cinR
      abolishes the production of 3OH,C14:1-HSL and also reduces the production of
      several other AHLs. This is thought to result from the expression of three other
      AHL production loci being affected by the absence of 3OH,C14:1-HSL. AHLs produced
      by these other loci include N-hexanoyl- and N-octanoyl-L-homoserine lactones and,
      unexpectedly, N-heptanoyl-L-homoserine lactone (C7-HSL). The expression of the
      rhiI gene on the symbiotic plasmid is greatly reduced in a cinI mutant, and the
      major regulatory effect appears to be mediated at least in part as a result of an
      effect on expression of RhiR, the regulator of rhiI. Thus, cinR and cinI appear
      to be at the top of a regulatory cascade or network that influences several AHL
      regulated quorum-sensing loci. The expression of cinI-lacZ fusions is
      significantly reduced (but not abolished) when the symbiosis plasmid pRL1JI is
      present, resulting in a reduction in the level of 3OH,C14:1-HSL produced.
      Mutation of cinI had little effect on growth or nodulation. However, plasmid
      transfer was affected, and the results obtained indicate that 3OH,C14:1-HSL
      produced by either the donor or the recipient in mating experiments can stimulate
      transfer of pRL1JI.

PMID- 10931308
TI  - Fusidic acid-resistant EF-G perturbs the accumulation of ppGpp.
AB  - Reductions in growth rate caused by fusidic acid-resistant EF-G mutants in
      Salmonella typhimurium correlate strongly with increased mean cell size. This is
      unusual because growth rate and cell size normally correlate positively. The
      global transcription regulator molecule ppGpp has a role in co-ordinating growth
      rate and division, and its basal level normally correlates inversely with cell
      size at division. We show that fusidic acid-resistant EF-G mutants have perturbed
      ppGpp basal levels during steady-state growth and perturbed induced levels during
      starvation. One mutation, fusA1, associated with the slowest growth rate and
      largest cell size, causes a reduction in the basal level of ppGpp to one-third of
      that found in the wild-type strain. Other fusA mutants with intermediate or wild
      type growth rates and cell sizes have either normal or increased basal levels of
      ppGpp. There is an inverse relationship between the basal level of ppGpp in vivo
      and the degree to which translation dependent on mutant EF-G is inhibited by
      ppGpp in vitro. This enhanced interaction between mutant EF-G and ppGpp
      correlates with an increased KM for GTP. Our results suggest that mutant EF-G
      modulates the production of ppGpp by the RelA (PSI) pathway. In conclusion,
      fusidic acid-resistant EF-G mutations alter the level of ppGpp and break the
      normal relationship between growth rate and cell size at division. It would not
      be surprising if other phenotypes associated with these mutants, such as loss of
      virulence, were also related to perturbations in ppGpp levels effected through
      altered transcription patterns.

PMID- 10931309
TI  - GUP1 and its close homologue GUP2, encoding multimembrane-spanning proteins
      involved in active glycerol uptake in Saccharomyces cerevisiae.
AB  - Many yeast species can utilize glycerol, both as a sole carbon source and as an
      osmolyte. In Saccharomyces cerevisiae, physiological studies have previously
      shown the presence of an active uptake system driven by electrogenic proton
      symport. We have used transposon mutagenesis to isolate mutants affected in the
      transport of glycerol into the cell. Here we present the identification of
      YGL084c, encoding a multimembrane-spanning protein, as being essential for proton
      symport of glycerol into S. cerevisiae. The gene is named GUP1 (glycerol uptake)
      and, for growth on glycerol, is important as a carbon and energy source. In
      addition, in strains deficient in glycerol production it also provides osmotic
      protection by the addition of glycerol. Another open reading frame (ORF),
      YPL189w, presenting a high degree of homology to YGL084c, similarly appears to be
      involved in active glycerol uptake in salt-containing glucose-based media in
      strains deficient in glycerol production. Analogously, this gene is named GUP2.
      To our knowledge, this is the first report on a gene product involved in active
      transport of glycerol in yeasts. Mutations with the same phenotypes occurred in
      two other ORFs of previously unknown function, YDL074c and YPL180w.

PMID- 10931310
TI  - Pathways for the utilization of N-acetyl-galactosamine and galactosamine in
      Escherichia coli.
AB  - Among enteric bacteria, the ability to grow on N-acetyl-galactosamine (GalNAc or
      Aga) and on D-galactosamine (GalN or Gam) differs. Thus, strains B, C and EC3132
      of Escherichia coli are Aga+ Gam+ whereas E. coli K-12 is Aga- Gam-, similarly to
      Klebsiella pneumoniae KAY2026, Klebsiella oxytoca M5a1 and Salmonella typhimurium
      LT2. The former strains carry a complete aga/kba gene cluster at 70.5 min of
      their gene map. These genes encode an Aga-specific phosphotransferase system
      (PTS) or IIAga (agaVWE) and a GalN-specific PTS or IIGam (agaBCD). Both PTSs
      belong to the mannose-sorbose family, i.e. the IIB, IIC and IID domains are
      encoded by different genes, and they share a IIA domain (agaF). Furthermore, the
      genes encode an Aga6P-deacetylase (agaA), a GalN6P deaminase (agaI), a tagatose
      bisphosphate aldolase comprising two different peptides (kbaYZ) and a putative
      isomerase (agaS), i.e. complete pathways for the transport and degradation of
      both amino sugars. The genes are organized in two adjacent operons (kbaZagaVWEFA
      and agaS kbaYagaBCDI) and controlled by a repressor AgaR. Its gene agaR is
      located upstream of kbaZ, and AgaR responds to GalNAc and GalN in the medium. All
      Aga- Gam- strains, however, carry a deletion covering genes agaW' EF 'A;
      consequently they lack active IIAga and IIGam PTSs, thus explaining their
      inability to grow on the two amino sugars. Remnants of a putative recombination
      site flank the deleted DNA in the various Aga- Gam- enteric bacteria. Derivatives
      with an Aga+ Gam- phenotype can be isolated from E. coli K-12. These retain the
      DeltaagaW' EF 'A deletion and carry suppressor mutations in the gat and nag genes
      for galactitol and N-acetyl-glucosamine metabolism, respectively, that allow
      growth on Aga but not on GalN.

PMID- 10931311
TI  - Functional roles of conserved amino acid residues surrounding the
      phosphorylatable histidine of the yeast phosphorelay protein YPD1.
AB  - The histidine-containing phosphotransfer (HPt) protein YPD1 is an osmoregulatory
      protein in yeast that facilitates phosphoryl transfer between the two response
      regulator domains associated with SLN1 and SSK1. Based on the crystal structure
      of YPD1 and the sequence alignment of YPD1 with other HPt domains, we site
      specifically engineered and purified several YPD1 mutants in order to examine the
      role of conserved residues surrounding the phosphorylatable histidine (H64).
      Substitution of the positively charged residues K67 and R90 destabilized the
      phospho-imidazole linkage, whereas substitution of G68 apparently reduces
      accessibility of H64. These findings, together with the effect of other
      mutations, provide biochemical support of the proposed functional roles of
      conserved amino acid residues of HPt domains.

PMID- 10931312
TI  - Site-specific DNA binding and bending by the Borrelia burgdorferi Hbb protein.
AB  - The Borrelia burgdorferi Hbb protein shows sequence similarity to members of the
      Escherichia coli HU/integration host factor (IHF) family of DNA accessory
      factors. We have overexpressed the hbb gene product in E. coli and purified the
      protein to near homogeneity. Biochemical analyses have revealed that Hbb has
      unique properties and is neither a strict HU nor IHF analogue. Hbb was found to
      bind specifically to a site in the putative origin of DNA replication between
      dnaA and dnaN. DNA footprinting studies have shown that this site is unrelated to
      the consensus sequence recognized by IHF proteins. Hbb induces a dramatic bend (>
      126 degrees ) at this site and was also shown to restrain negative supercoils
      efficiently upon DNA binding. These features of the protein suggest that Hbb may
      act as a DNA accessory factor that facilitates the assembly of higher order
      protein-DNA complexes, such as those involved in DNA replication, transcription,
      recombination, packaging and perhaps other DNA metabolic processes unique to
      Borrelia.

PMID- 10931313
TI  - Genes encoding synthetases of cyclic depsipeptides, anabaenopeptilides, in
      Anabaena strain 90.
AB  - Anabaena strain 90 produces three hepatotoxic heptapeptides (microcystins), two
      seven-residue depsipeptides called anabaenopeptilide 90A and 90B, and three six
      residue peptides called anabaenopeptins. The anabaenopeptilides belong to a group
      of cyanobacterial depsipeptides that share the structure of a six-amino-acid ring
      with a side-chain. Despite their similarity to known cyclic peptide toxins, no
      function has been assigned to the anabaenopeptilides. Degenerate oligonucleotide
      primers based on the conserved amino acid sequences of other peptide synthetases
      were used to amplify DNA from Anabaena 90, and the resulting polymerase chain
      reaction (PCR) products were used to identify a peptide synthetase gene cluster.
      Four genes encoding putative anabaenopeptilide synthetase domains were
      characterized. Three genes, apdA, apdB and apdD, contain two, four and one
      module, respectively, encoding a total of seven modules for activation and
      peptide bond formation of seven L-amino acids. Modules five and six also carry
      methyltransferase-like domains. Before the first module, there is a region
      similar in amino acid sequence to formyltransferases. A fourth gene (apdC),
      between modules six and seven, is similar in sequence to halogenase genes. Thus,
      the order of domains is co-linear with the positions of amino acid residues in
      the finished peptide. A mutant of Anabaena 90 was made by inserting a
      chloramphenicol resistance gene into the apdA gene. DNA amplification by PCR
      confirmed the insertion. Mass spectrometry analysis showed that
      anabaenopeptilides are not made in the mutant strain, but other peptides, such as
      microcystins and anabaenopeptins, are still produced by the mutant.

PMID- 10931314
TI  - Novel effects of a transposon insertion in the Vibrio fischeri glnD gene: defects
      in iron uptake and symbiotic persistence in addition to nitrogen utilization.
AB  - Vibrio fischeri is the sole species colonizing the light-emitting organ of the
      Hawaiian squid, Euprymna scolopes. Upon entering the nascent light organ of a
      newly hatched juvenile squid, the bacteria undergo morphological and
      physiological changes that include the loss of flagellation and the induction of
      bioluminescence. These and other events reveal a pattern of genetic regulation
      that is a response to the colonization of host tissue. In this study, we isolated
      and characterized a glnD:mTn5Cm mutant of V. fischeri. In addition to the
      predicted defects in the efficiency of nitrogen utilization, this glnD mutant had
      an unexpected reduction in the ability to produce siderophore and grow under iron
      limiting conditions. Although the glnD mutant could colonize juvenile squid
      normally over the first 24 h, it was subsequently unable to persist in the light
      organ to the usual extent. This persistence phenotype was more severe if the
      mutant was pregrown under iron-limiting conditions before inoculation, but could
      be ameliorated by the presence of excess iron. These results indicate that the
      ability to respond to iron limitation may be an important requirement in the
      developing symbiosis. Supplying the glnD gene in trans restored normal efficiency
      of nitrogen use, iron sequestration and colonization phenotypes to the
      glnD:mTn5Cm mutant; thus, there appears to be a genetic and/or metabolic linkage
      between nitrogen sensing, siderophore synthesis and symbiosis competence in V.
      fischeri that involves the glnD gene.

PMID- 10931315
TI  - Resolution of holliday junctions by RuvABC prevents dimer formation in rep
      mutants and UV-irradiated cells.
AB  - In this work, we present evidence that indicates that RuvABC proteins resolve
      Holliday junctions in a way that prevents dimer formation in vivo. First,
      although arrested replication forks are rescued by recombinational repair in
      cells deficient for the Rep helicase, rep mutants do not require the XerCD
      proteins or the dif site for viability. This shows that the recombination events
      at arrested replication forks are generally not accompanied by the formation of
      chromosome dimers. Secondly, resolution of dimers into monomers is essential in
      the rep ruv strain because of an increased frequency of RecFOR recombination
      events in the chromosome of this mutant. This suggests that, in the absence of
      the Ruv proteins, chromosomal recombination leads to frequent dimerization.
      Thirdly, dif or xerC mutations increase the UV sensitivity of ruv-deficient cells
      100-fold, whereas they do not confer UV sensitivity to ruv+ cells. This shows
      that recombinational repair of UV lesions is not accompanied by dimer formation
      provided that the RuvABC proteins are active. The requirement for dimer
      resolution in ruv strains is suppressed by the expression of the RusA Holliday
      junction resolvase; therefore, RusA also prevents dimer formation. We conclude
      that the inviability arising from a high frequency of dimer formation in rep or
      UV-irradiated cells is only observed in the absence of known enzymes that resolve
      Holliday junctions.

PMID- 10931316
TI  - Functional mapping of the Yersinia enterocolitica adhesin YadA. Identification Of
      eight NSVAIG - S motifs in the amino-terminal half of the protein involved in
      collagen binding.
AB  - The virulence plasmid-encoded YadA of Yersinia enterocolitica serotype O:3 is a
      430-amino-acid outer membrane protein, synthesized with a 25-amino-acid signal
      peptide. YadA forms homotrimeric surface structures that function as adhesin
      between bacteria and collagen as well as other host proteins. The structure
      function relationships of YadA were studied, and the collagen-binding
      determinants of YadA were located to its amino-terminal half. Collagen did not
      bind to any of the overlapping 16-mer YadA peptides, indicating that the collagen
      binding site of YadA is conformational. Epitope mapping of YadA identified 12
      linear antigenic epitopes altogether. Seven epitopes were uniquely recognized by
      an anti-YadA antiserum able to inhibit collagen binding. Four of these epitopes
      shared a motif NSVAIG-S that is repeated eight times within the N-terminal half
      of YadA. Site-directed mutagenesis showed that these motifs are absolutely
      required for YadA-mediated collagen binding, revealing a novel type of collagen
      binding mechanism.

PMID- 10931317
TI  - Repeat-associated phase variable genes in the complete genome sequence of
      Neisseria meningitidis strain MC58.
AB  - Phase variation, mediated through variation in the length of simple sequence
      repeats, is recognized as an important mechanism for controlling the expression
      of factors involved in bacterial virulence. Phase variation is associated with
      most of the currently recognized virulence determinants of Neisseria
      meningitidis. Based upon the complete genome sequence of the N. meningitidis
      serogroup B strain MC58, we have identified tracts of potentially unstable simple
      sequence repeats and their potential functional significance determined on the
      basis of sequence context. Of the 65 potentially phase variable genes identified,
      only 13 were previously recognized. Comparison with the sequences from the other
      two pathogenic Neisseria sequencing projects shows differences in the length of
      the repeats in 36 of the 65 genes identified, including 25 of those not
      previously known to be phase variable. Six genes that did not have differences in
      the length of the repeat instead had polymorphisms such that the gene would not
      be expected to be phase variable in at least one of the other strains. A further
      12 candidates did not have homologues in either of the other two genome
      sequences. The large proportion of these genes that are associated with
      frameshifts and with differences in repeat length between the neisserial genome
      sequences is further corroborative evidence that they are phase variable. The
      number of potentially phase variable genes is substantially greater than for any
      other species studied to date, and would allow N. meningitidis to generate a very
      large repertoire of phenotypes through expression of these genes in different
      combinations. Novel phase variable candidates identified in the strain MC58
      genome sequence include a spectrum of genes encoding glycosyltransferases, toxin
      related products, and metabolic activities as well as several
      restriction/modification and bacteriocin-related genes and a number of open
      reading frames (ORFs) for which the function is currently unknown. This suggests
      that the potential role of phase variation in mediating bacterium-host
      interactions is much greater than has been appreciated to date. Analysis of the
      distribution of homopolymeric tract lengths indicates that this species has
      sequence-specific mutational biases that favour the instability of sequences
      associated with phase variation.

PMID- 10931318
TI  - The DB case: pattern matching evidence is not significant.

PMID- 10931319
TI  - Multidrug resistance mechanisms: drug efflux across two membranes.
AB  - A set of multidrug efflux systems enables Gram-negative bacteria to survive in a
      hostile environment. This review focuses on the structural features and the
      mechanism of major efflux pumps of Gram-negative bacteria, which expel from the
      cells a remarkably broad range of antimicrobial compounds and produce the
      characteristic intrinsic resistance of these bacteria to antibiotics, detergents,
      dyes and organic solvents. Each efflux pump consists of three components: the
      inner membrane transporter, the outer membrane channel and the periplasmic
      lipoprotein. Similar to the multidrug transporters from eukaryotic cells and Gram
      positive bacteria, the inner membrane transporters from Gram-negative bacteria
      recognize and expel their substrates often from within the phospholipid bilayer.
      This efflux occurs without drug accumulation in the periplasm, implying that
      substrates are pumped out across the two membranes directly into the medium.
      Recent data suggest that the molecular mechanism of the drug extrusion across a
      two-membrane envelope of Gram-negative bacteria may involve the formation of the
      membrane adhesion sites between the inner and the outer membranes. The
      periplasmic components of these pumps are proposed to cause a close membrane
      apposition as the complexes are assembled for the transport.

PMID- 10931320
TI  - Escherichia coli translocase: the unravelling of a molecular machine.
AB  - Protein translocation across the bacterial cytoplasmic membrane has been studied
      extensively in Escherichia coli. The identification of the components involved
      and subsequent reconstitution of the purified translocation reaction have defined
      the minimal constituents that allowed extensive biochemical characterization of
      the so-called translocase. This functional enzyme complex consists of the SecYEG
      integral membrane protein complex and a peripherally bound ATPase, SecA. Under
      translocation conditions, four SecYEG heterotrimers assemble into one large
      protein complex, forming a putative protein-conducting channel. This tetrameric
      arrangement of SecYEG complexes and the highly dynamic SecA dimer together form a
      proton-motive force- and ATP-driven molecular machine that drives the stepwise
      translocation of targeted polypeptides across the cytoplasmic membrane. Recent
      findings concerning the translocase structure and mechanism of protein
      translocation are discussed and shine new light on controversies in the field.

PMID- 10931321
TI  - Structure and function of bacterial outer membrane proteins: barrels in a
      nutshell.
AB  - The outer membrane protects Gram-negative bacteria against a harsh environment.
      At the same time, the embedded proteins fulfil a number of tasks that are crucial
      to the bacterial cell, such as solute and protein translocation, as well as
      signal transduction. Unlike membrane proteins from all other sources, integral
      outer membrane proteins do not consist of transmembrane alpha-helices, but
      instead fold into antiparallel beta-barrels. Over recent years, the atomic
      structures of several outer membrane proteins, belonging to six families, have
      been determined. They include the OmpA membrane domain, the OmpX protein,
      phospholipase A, general porins (OmpF, PhoE), substrate-specific porins (LamB,
      ScrY) and the TonB-dependent iron siderophore transporters FhuA and FepA. These
      crystallographic studies have yielded invaluable insight into and decisively
      advanced the understanding of the functions of these intriguing proteins. Our
      review is aimed at discussing their common principles and peculiarities as well
      as open questions associated with them.

PMID- 10931322
TI  - The Escherichia coli aquaporin-Z water channel.
AB  - The membrane pathway of the rapid fluxes of water by which microorganisms adapt
      promptly to abrupt changes in environmental osmolality have begun to be
      understood since the discovery of the Escherichia coli aquaporin-Z water channel,
      AqpZ. As in animals and plants, aquaporins are variously represented among
      microorganisms, in which 31 homologous genes have already been identified in
      eubacteria, Archaea, fungi and protozoa. The AqpZ channel is selectively
      permeable to water, although other functions are not excluded. Consistent with a
      conservation over the course of evolution, AqpZ and AQP1, a human counterpart,
      share similar structures. The aqpZ gene is growth phase and osmotically
      regulated. AqpZ has a role in both the short- and the long-term osmoregulatory
      response and is required by rapidly growing cells. AqpZ-like proteins seem to be
      necessary for the virulence expressed by some pathogenic bacteria. Microbial
      aquaporins are also likely to be involved in spore formation and/or germination.
      Additional roles may still be unknown. The use of AqpZ as a model system will
      continue to provide insight into the understanding of the importance of
      aquaporins.

PMID- 10931323
TI  - LcrQ/YscM1, regulators of the Yersinia yop virulon, are injected into host cells
      by a chaperone-dependent mechanism.
AB  - Pathogenic Yersinia species employ type III machines to secrete YopBDR into the
      extracellular milieu. After attaching to host cells, yersiniae transform the type
      III machinery into an injection device and target YopEHMNOPT into eukaryotic
      cells. Yersinia pseudotuberculosis LcrQ is a transcriptional regulator that
      prevents the expression of yop genes. We report that LcrQ is injected into
      eukaryotic cells. YscM1, the transciptional regulator of Yersinia enterocolitica,
      is also injected into eukaryotic cells, whereas the related YscM2 protein remains
      associated with bacterial cells. Type III targeting of YscM1 requires binding to
      the SycH chaperone. Chaperone binding as well as depletion of YscM1 and YscM2
      from the cytoplasm of Y. enterocolitica causes an increase in yop expression,
      whereas a block in regulator export reduces expression. We propose a model
      whereby the chaperone-mediated injection of LcrQ/YscM1 functions as a regulatory
      switch for bacteria that are attached to host cells, triggering the expression of
      Yops that travel the type III targeting pathway.

PMID- 10931324
TI  - Iron acquisition and virulence in Helicobacter pylori: a major role for FeoB, a
      high-affinity ferrous iron transporter.
AB  - The genome sequence of Helicobacter pylori suggests that this bacterium possesses
      several Fe acquisition systems, including both Fe2+- and Fe3+-citrate
      transporters. The role of these transporters was investigated by generating
      insertion mutants in feoB, tonB, fecA1 and fecDE. Fe transport in the feoB mutant
      was approximately 10-fold lower than in the wild type (with 0.5 microM Fe),
      irrespective of whether Fe was supplied in the Fe2+ or Fe3+ form. In contrast,
      transport rates were unaffected by the other mutations. Complementation of the
      feoB mutation fully restored both Fe2+ and Fe3+ transport. The growth inhibition
      exhibited by the feoB mutant in Fe-deficient media was relieved by human holo
      transferrin, holo-lactoferrin and Fe3+-dicitrate, but not by FeSO4. The feoB
      mutant had less cellular Fe and was more sensitive to growth inhibition by
      transition metals in comparison with the wild type. Biphasic kinetics of Fe2+
      transport in the wild type suggested the presence of high- and low-affinity
      uptake systems. The high-affinity system (apparent Ks = 0.54 microM) is absent in
      the feoB mutant. Transport via FeoB is highly specific for Fe2+ and was inhibited
      by FCCP, DCCD and vanadate, indicating an active process energized by ATP.
      Ferrozine inhibition of Fe2+ and Fe3+ uptake implied the concerted involvement of
      both an Fe3+ reductase and FeoB in the uptake of Fe supplied as Fe3+. Taken
      together, the results are consistent with FeoB-mediated Fe2+ uptake being a major
      pathway for H. pylori Fe acquisition. feoB mutants were unable to colonize the
      gastric mucosa of mice, indicating that FeoB makes an important contribution to
      Fe acquisition by H. pylori in the low-pH, low-O2 environment of the stomach.

PMID- 10931325
TI  - Intracellular localization and processing of Pseudomonas aeruginosa ExoS in
      eukaryotic cells.
AB  - ExoS is a type III cytotoxin of Pseudomonas aeruginosa, which modulates two
      eukaryotic signalling pathways. The N-terminus (residues 1-234) is a GTPase
      activating protein (GAP) for RhoGTPases, while the C-terminus (residues 232-453)
      encodes an ADP-ribosyltransferase. Utilizing a series of N-terminal deletion
      peptides of ExoS and an epitope-tagged full-length ExoS, two independent domains
      have been identified within the N-terminus of ExoS that are involved in
      intracellular localization and expression of GAP activity. N-terminal peptides of
      ExoS localized to the perinuclear region of CHO cells, and a membrane
      localization domain was localized between residues 36 and 78 of ExoS. The
      capacity to elicit CHO cell rounding and express GAP activity resided within
      residues 90-234 of ExoS, which showed that membrane localization was not required
      to elicit actin reorganization. ExoS was present in CHO cells as a full-length
      form, which fractionated with membranes, and as an N-terminally processed
      fragment, which localized to the cytosol. Thus, ExoS localizes in eukaryotic
      cells to the perinuclear region and is processed to a soluble fragment, which
      possesses both the GAP and ADP-ribosyltransferase activities.

PMID- 10931326
TI  - The cis requirements for transcriptional activation by HilA, a virulence
      determinant encoded on SPI-1.
AB  - In several models of pathogenesis, Salmonella requires genes encoded on
      Salmonella pathogenicity island 1 (SPI-1) for virulence. In Salmonella enterica
      serovar Typhimurium (S. typhimurium), most SPI-1 genes are arranged in operons
      and are co-ordinately regulated in response to environmental signals via the SPI
      1-encoded protein HilA. In order to understand how HilA controls the
      transcription of SPI-1 genes, we have analysed the invF and prgH promoters. We
      have reconstituted HilA-dependent activation of both promoters in Escherichia
      coli by supplying hilA on a plasmid, strongly suggesting that HilA acts directly
      on the promoters. By analysing the HilA-dependent activity of deletions and
      mutations in PinvF, we identified cis elements necessary for HilA-dependent
      activation. Through biochemical studies, we have defined a probable HilA-binding
      sequence in the invF promoter. This 'HilA box' is intact in the minimal promoter
      identified through deletion analysis, and it is disrupted in one class of PinvF
      mutants that has reduced activation by HilA. The prgH promoter also contains a
      HilA box in the same position relative to the +1 of transcription. This work is
      the first to connect HilA-dependent environmental regulation with a specific
      sequence in a SPI-1 virulence gene promoter.

PMID- 10931327
TI  - Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis
      and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague
      bacillus is most closely related to and has evolved from Y. pseudotuberculosis
      serotype O:1b.
AB  - One of the most virulent and feared bacterial pathogens is Yersinia pestis, the
      aetiologic agent of bubonic plague. Characterization of the O-antigen gene
      clusters of 21 serotypes of Yersinia pseudotuberculosis and the cryptic O-antigen
      gene cluster of Y. pestis showed that the plague bacillus is most closely related
      to and has evolved from Y. pseudotuberculosis serotype O:1b. The nucleotide
      sequences of both gene clusters (about 20.5 kb each) were determined and compared
      to identify the differences that caused the silencing of the Y. pestis gene
      cluster. At the nucleotide sequence level, the loci were 98.9% identical and, of
      the 17 biosynthetic genes identified from the O:1b gene cluster, five were
      inactivated in the Y. pestis cluster, four by insertions or deletions of one
      nucleotide and one by a deletion of 62 nucleotides. Apparently, the expression of
      the O-antigen is not beneficial for the virulence or to the lifestyle of Y.
      pestis and, therefore, as one step in the evolution of Y. pestis, the O-antigen
      gene cluster was inactivated.

PMID- 10931328
TI  - Membrane topology of the Mep/Amt family of ammonium transporters.
AB  - The Mep/Amt proteins constitute a new family of transport proteins that are
      ubiquitous in nature. Members from bacteria, yeast and plants have been
      identified experimentally as high-affinity ammonium transporters. We have
      determined the topology of AmtB, a Mep/Amt protein from Escherichia coli, as a
      representative protein for the complete family. This was established using a
      minimal set of AmtB-PhoA fusion proteins with a complementary set of AmtB-LacZ
      fusions. These data, accompanied by an in silico analysis, indicate that the
      majority of the Mep/Amt proteins contain 11 membrane-spanning helices, with the N
      terminus on the exterior face of the membrane and the C-terminus on the interior.
      A small subset, including E. coli AmtB, probably have an additional twelfth
      membrane-spanning region at the N-terminus. Addition of PhoA or LacZ alpha
      peptide to the C-terminus of E. coli AmtB resulted in complete loss of transport
      activity, as judged by measurements of [14C]-methylammonium uptake. This C
      terminal region, along with four membrane-spanning helices, contains multiple
      residues that are conserved within the Mep/Amt protein family. Structural
      modelling of the E. coli AmtB protein suggests a number of secondary structural
      features that might contribute to function, including a putative ammonium binding
      site on the periplasmic face of the membrane at residue Asp-182. The implications
      of these results are discussed in relation to the structure and function of the
      related human Rhesus proteins.

PMID- 10931329
TI  - Role of the Gp16 lytic transglycosylase motif in bacteriophage T7 virions at the
      initiation of infection.
AB  - The predicted catalytic glutamate residue for transglycosylase activity of
      bacteriophage T7 gp16 is not essential for phage growth, but is shown to be
      beneficial during infection of Escherichia coli cells grown to high cell density,
      conditions in which murein is more highly cross-linked. In the absence of the
      putative transglycosylase, internalization of the phage genome is significantly
      delayed during infection. The lytic transglycosylase motif of gp16 is essential
      for phage growth at temperatures below 20 degrees C, indicating that these growth
      conditions also lead to increased cross-linking of peptidoglycan. Overexpression
      of sltY, E. coli soluble lytic transglycosylase, partially complements the defect
      in infection of mutant phage particles, allowing them to infect at higher
      efficiencies. Conversely, an sltY deletion increases the latent period of wild
      type phage.

PMID- 10931330
TI  - Bacteriophage PRD1 DNA entry uses a viral membrane-associated transglycosylase
      activity.
AB  - Amino acid sequence analyses have indicated that the amino-terminal part of
      bacteriophage PRD1 structural protein P7 carries a conserved transglycosylase
      domain. We analysed wild-type PRD1 and different mutant particles in zymograms
      and found a glycolytic activity that was associated with protein P7. This is the
      first time a putative bacteriophage or plasmid lytic transglycosylase has been
      shown to have an enzymatic activity. In the absence of protein P7, the phage DNA
      replication and host cell lysis were delayed. Gene VII of PRD1 is known to encode
      proteins P7 and P14. In this investigation, the open reading frame coding for P14
      was mapped to the 3' end of gene VII. Proteins P7 and P14 probably form a
      heteromultimeric complex, which is located at the particle vertices and is
      involved in the early steps of the PRD1 life cycle

PMID- 10931331
TI  - 'Intergenic' blr gene in Escherichia coli encodes a 41-residue membrane protein
      affecting intrinsic susceptibility to certain inhibitors of peptidoglycan
      synthesis.
AB  - In the annotation of genomic sequences, small open reading frames (ORFs) are
      often neglected, particularly if they have no homology to other ORFs or proteins.
      A mini-TnphoA insertion in a 602 bp 'intergenic' region of the Escherichia coli
      chromosome at genomic nucleotide 1702674 gave rise to a membrane-bound PhoA
      fusion protein and a two- to fourfold increase in the intrinsic susceptibility to
      a wide spectrum of beta-lactam antibiotics without affecting beta-lactamase
      activity or susceptibility to tetracycline, chloramphenicol, gentamicin or
      quinolones. Susceptibility was also increased to cycloserine and bacitracin, but
      not to fosfomycin or valinomycin; these drugs, like beta-lactams, inhibit
      peptidoglycan synthesis, although by different mechanisms. A clone bearing only
      358 bp of this 'blr' region restored resistance to the parental level. Two amber
      mutations in the clone prevented such restoration and were counteracted by an
      amber suppressor, proving that the active species is a protein. The Blr protein
      has 41 amino acids, with a single predicted transmembrane helix, but no clear
      homology to any other protein. A transcriptional start exists 39 bp upstream from
      the translational start. The membrane location of Blr suggests that it may be
      part of an efflux pump or involved in murein metabolism. The results indicate
      that genes for other very small functional proteins may lie within 'intergenic'
      regions.

PMID- 10931332
TI  - Transcriptional induction of the conserved alternative sigma factor RpoS in
      Escherichia coli is dependent on BarA, a probable two-component regulator.
AB  - The stationary phase expression of many conserved, adaptive bacterial proteins is
      dependent on RpoS, a second vegetative sigma factor. The regulation of RpoS
      itself, however, is complex and not fully understood, particularly at the level
      of transcription. In this report, we show that the observed hydrogen peroxide
      sensitivity of a mutant defective in expression of barA, a bacterial virulence
      factor, can be explained by a reduction in catalase activity, an RpoS-controlled
      function. Levels of katE mRNA, encoding the major catalase of Escherichia coli,
      were much lower in the barA mutant, suggesting that BarA is required for the
      expression of this RpoS-regulated gene. Expression of another RpoS-regulated
      gene, osmY, was also found to be severely reduced in the barA mutant. Employing
      Western analyses with anti-RpoS antisera and Northern analyses using probes
      specific for rpoS, we found that BarA is required for the exponential phase
      induction of RpoS itself. Operon lacZ fusion expression studies and Northern
      analyses indicate that BarA itself is maximally expressed in early exponential
      phase cultures immediately preceding the transcriptional induction of RpoS.
      Results of primer extension studies indicate that exponential phase expression
      from the rpoSp1 promoter is reduced by more than 85% in a barA mutant but could
      be efficiently complemented by a plasmid-borne copy of barA in trans. These
      results suggest that regulatory signals that are operant in exponentially growing
      cultures play an important role in effecting stationary phase gene expression.

PMID- 10931333
TI  - Response of Saccharomyces cerevisiae to severe osmotic stress: evidence for a
      novel activation mechanism of the HOG MAP kinase pathway.
AB  - The HOG/p38 MAP kinase route is an important stress-activated signal transduction
      pathway that is well conserved among eukaryotes. Here, we describe a novel
      mechanism of activation of the HOG pathway in budding yeast. This mechanism
      operates upon severe osmostress conditions (1.4 M NaCl) and is independent of the
      Sln1p and Sho1p osmosensors. The alternative input feeds into the HOG pathway
      MAPKK Pbs2p and requires activation of Pbs2p by phosphorylation. We show that,
      upon severe osmotic shock, Hog1p nuclear accumulation and phosphorylation is
      delayed compared with mild stress. Moreover, both events lost their transient
      pattern, presumably because of the absence of negative feedback mediated by Ptp2p
      tyrosine phosphatase, which we found to be localized in the nucleus. Under severe
      osmotic stress conditions, the delayed nuclear accumulation correlates with a
      delay in stress-responsive gene expression. Severe osmoshock leads to a situation
      in which active and nuclear-localized Hog1p is transiently unable to induce
      transcription of osmotic stress-responsive genes. It also appeared from our
      studies that the Sho1p osmosensor is less active under severe osmotic stress
      conditions, whereas the Sln1p/Ypd1p/Ssk1p sensor and signal transducer functions
      normally under these circumstances.

PMID- 10931334
TI  - Identification and characterization of SarH1, a new global regulator of virulence
      gene expression in Staphylococcus aureus.
AB  - The global regulators agr (accessory gene regulator) and sarA (staphylococcal
      accessory regulator) have been reported to be both activators and repressors of
      virulence gene expression in Staphylococcus aureus. How the effector of the agr
      system, RNAIII, interacts with target gene promoters is unknown. SarA, on the
      other hand, is a DNA-binding protein, which binds to conserved DNA motifs
      immediately upstream of both positively and negatively regulated promoters. Here,
      we searched for additional regulators that could explain the differential effects
      of RNAIII and SarA. Four differently regulated genes (hla, alpha-toxin; hld,
      RNAIII; spa, protein A; ssp, serine protease) were analysed for binding of
      potential regulatory proteins to the corresponding promoter DNA fragments, linked
      to magnetic beads. One protein (29 kDa), with affinity for all four promoters,
      showed a high degree of similarity to SarA and was named SarH1 (Sar homologue 1).
      Expression of sarH1 was strongly repressed by sarA and agr. Analysis of hla, hld,
      ssp and spa mRNAs in sarH1, sarA and agr mutants, and in sarA/sarH1 and agr/sarH1
      double mutants, revealed that sarH1 has a strong repressive effect on hla and an
      activating effect on spa transcription. SDS-PAGE analysis of secreted proteins
      from the different mutants showed that the production of several other
      exoproteins was affected by sarH1. In conclusion, we show that both the agr
      dependent suppression of protein A production and the sarA-dependent stimulation
      of alpha-toxin production is mediated via a new regulator, SarH1, which belongs
      to a family of Sar homologues.

PMID- 10931335
TI  - Cell division inhibitors SulA and MinC/MinD block septum formation at different
      steps in the assembly of the Escherichia coli division machinery.
AB  - SulA and MinCD are specific inhibitors of cell division in Escherichia coli. In
      this paper, size exclusion chromatography was used to study the effect of the
      SulA and MinCD division inhibitors on the oligomerization state of endogenous
      FtsZ in cytoplasmic extracts, and immunofluorescence microscopy was used to
      determine the effect of SulA and MinCD on the formation of FtsZ, FtsA and ZipA
      rings at potential division sites. SulA prevented the formation of high-molecular
      weight FtsZ polymers by interfering with FtsZ dimerization and subsequent
      oligomerization. In contrast, the MinCD division inhibitor did not prevent the
      oligomerization of FtsZ in the cell extracts or the formation of FtsZ and ZipA
      ring structures in vivo. However, MinCD did prevent the formation of FtsA rings.
      Increased expression of ftsA suppressed MinCD-induced division inhibition, but
      had no effect on SulA-induced division inhibition. These results indicate that
      MinCD blocks the assembly of the septation machinery at a later step than SulA,
      at the stage at which FtsA is added to the FtsZ ring.

PMID- 10931336
TI  - The outer membrane protein, antigen 43, mediates cell-to-cell interactions within
      Escherichia coli biofilms.
AB  - Transcription of the agn43 locus, which specifies an outer membrane protein of
      Escherichia coli, is regulated in a phase-variable fashion by the OxyR-DNA
      binding protein and Dam methylase. Despite its well-characterized regulation, the
      function of Ag43 has remained elusive until now. Previous studies indicated that
      Ag43 mediates autoaggregation of certain strains of E. coli in liquid culture.
      Given this phenotype, we examined the role of Ag43 in biofilm formation. Here, we
      report that Ag43 contributes to E. coli biofilm formation in glucose-minimal
      medium, but not in Luria-Bertani broth. In addition, we show that flagellar
      mediated motility is required for biofilm formation in both rich and minimal
      environments. Altogether, our results suggest that E. coli uses both common and
      specific gene sets for the development of biofilms under various growth
      conditions.

PMID- 10931337
TI  - Acid activation of Helicobacter pylori vacuolating cytotoxin (VacA) results in
      toxin internalization by eukaryotic cells.
AB  - Helicobacter pylori VacA is a secreted toxin that induces multiple structural and
      functional alterations in eukaryotic cells. Exposure of VacA to either acidic or
      alkaline pH ('activation') results in structural changes in the protein and a
      marked enhancement of its cell-vacuolating activity. However, the mechanism by
      which activation leads to increased cytotoxicity is not well understood. In this
      study, we analysed the binding and internalization of [125I]-VacA by HeLa cells.
      We detected no difference in the binding of untreated and activated [125I]-VacA
      to cells. Binding of acid-activated [125I]-VacA to cells at 4 degrees C was not
      saturable, and was only partially inhibited by excess unlabelled toxin. These
      results suggest that VacA binds either non-specifically or to an abundant, low
      affinity receptor on HeLa cells. To study internalization of VacA, we used a
      protease protection assay. Analysis by SDS-PAGE and autoradiography indicated
      that the intact 87 kDa toxin was internalized in a time-dependent process at 37
      degrees C but not at 4 degrees C. Furthermore, internalization of the intact
      toxin was detected only if VacA was acid or alkaline activated before being added
      to cells. The internalization of activated [125I]-VacA was not substantially
      inhibited by the presence of excess unlabelled toxin, but was blocked if cells
      were depleted of cellular ATP by the addition of sodium azide and 2-deoxy-D
      glucose. These results indicate that acid or alkaline pH-induced structural
      changes in VacA are required for VacA entry into cells, and that internalization
      of the intact 87 kDa toxin is required for VacA cytotoxicity.

PMID- 10931339
TI  - Plasmid and chromosome partitioning: surprises from phylogeny.
AB  - Plasmids encode partitioning genes (par) that are required for faithful plasmid
      segregation at cell division. Initially, par loci were identified on plasmids,
      but more recently they were also found on bacterial chromosomes. We present here
      a phylogenetic analysis of par loci from plasmids and chromosomes from
      prokaryotic organisms. All known plasmid-encoded par loci specify three
      components: a cis-acting centromere-like site and two trans-acting proteins that
      form a nucleoprotein complex at the centromere (i.e. the partition complex). The
      proteins are encoded by two genes in an operon that is autoregulated by the par
      encoded proteins. In all cases, the upstream gene encodes an ATPase that is
      essential for partitioning. Recent cytological analyses indicate that the ATPases
      function as adaptors between a host-encoded component and the partition complex
      and thereby tether plasmids and chromosomal origin regions to specific
      subcellular sites (i.e. the poles or quarter-cell positions). Two types of
      partitioning ATPases are known: the Walker-type ATPases encoded by the par/sop
      gene family (type I partitioning loci) and the actin-like ATPase encoded by the
      par locus of plasmid R1 (type II partitioning locus). A phylogenetic analysis of
      the large family of Walker type of partitioning ATPases yielded a surprising
      pattern: most of the plasmid-encoded ATPases clustered into distinct subgroups.
      Surprisingly, however, the par loci encoding these distinct subgroups have
      different genetic organizations and thus divide the type I loci into types Ia and
      Ib. A second surprise was that almost all chromosome-encoded ATPases, including
      members from both Gram-negative and Gram-positive Bacteria and Archaea, clustered
      into one distinct subgroup. The phylogenetic tree is consistent with lateral gene
      transfer between Bacteria and Archaea. Using database mining with the ParM ATPase
      of plasmid R1, we identified a new par gene family from enteric bacteria. These
      type II loci, which encode ATPases of the actin type, have a genetic organization
      similar to that of type Ib loci.

PMID- 10931338
TI  - Inhibition of glutamine synthetase II expression by the product of the gstI gene.
AB  - We report the identification of a previously unrecognized gene that is involved
      in the regulation of the Rhizobium leguminosarum glnII (glutamine synthetase II)
      gene. This gene, which is situated immediately upstream of glnII, was identified
      by means of a deletion/complementation analysis performed in the heterologous
      background of Klebsiella pneumoniae. It has been designated gstI (glutamine
      synthetase translational Inhibitor) because, when a complete version of gstI is
      present, it is possible to detect glnII-specific mRNA, but neither GSII activity
      nor GSII protein. The gstI gene encodes a small (63 amino acids) protein, which
      acts in cis or in trans with respect to glnII and is transcribed divergently with
      respect to glnII from a promoter that was found to be strongly repressed by the
      nitrogen transcriptional regulator NtrC. A mutated version of GstI lacking the
      last 14 amino acids completely lost its capacity to repress glnII expression. Our
      results indicate that gstI mediates the translation inhibition of glnII mRNA and,
      based on in silico analyses, a mechanism for GstI action is proposed.

PMID- 10931340
TI  - Control of plasmid DNA replication by iterons: no longer paradoxical.
AB  - Replication origins of a family of bacterial plasmids have multiple sites, called
      iterons, for binding a plasmid-specific replication initiator protein. The iteron
      initiator interactions are essential for plasmid replication as well as for
      inhibition of plasmid over-replication. The inhibition increases with plasmid
      copy number and eventually shuts plasmid replication off completely. The
      mechanism of inhibition appears to be handcuffing, the coupling of origins via
      iteron-bound initiators that block origin function. The probability of a trans
      reaction such as handcuffing is expected to increase with plasmid copy number and
      diminish with increases in cell volume, explaining how the copy number can be
      maintained in a growing cell. Control is also exerted at the level of initiator
      synthesis and activation by chaperones. We propose that increases in active
      initiators promote initiation by overcoming handcuffing, but handcuffing
      dominates when the copy number reaches a threshold. Handcuffing should be
      ultrasensitive to copy number, as the negative control by iterons can be
      stringent (switch-like).

PMID- 10931341
TI  - Plasmid rolling-circle replication: recent developments.
AB  - It is now well established that a large majority of small, multicopy plasmids of
      Gram-positive bacteria use the rolling-circle (RC) mechanism for their
      replication. Furthermore, the host range of RC plasmids now includes Gram
      negative organisms as well as archaea. RC plasmids can be broadly classified into
      at least five families, individual members of which are spread among widely
      different bacteria. There is significant homology in the basic replicons of
      plasmids belonging to a particular family, and there is compelling evidence that
      such plasmids have evolved from common ancestors. Major advances have recently
      been made in our understanding of plasmid RC replication, including the
      characterization of the biochemical activities of the plasmid initiator proteins
      and their interaction with the double-strand origin, the domain structure of the
      initiator proteins and the molecular basis for the function of single-strand
      origins in plasmid lagging strand synthesis. Over the past several years, there
      has been a 'renaissance' in studies on RC replication as a result of the
      discovery that many plasmids replicate by this mechanism, and studies in the next
      few years are likely to reveal new and novel mechanisms used by RC plasmids for
      their regulated replication.

PMID- 10931342
TI  - Paradigms of plasmid organization.
AB  - Plasmids are extrachromosomal elements built from a selection of generally quite
      well understood survival and propagation functions, including replication,
      partitioning, multimer resolution, post-segregational killing and conjugative
      transfer. Evolution has favoured clustering of these modules to form plasmid
      cores or backbones. Co-regulation of these core genes can also provide advantages
      that favour retention of the backbone organization. Tumour-inducing and symbiosis
      determining plasmids appear to co-regulate replication and transfer in response
      to cell density, both being stimulated at high density. Broad-host-range plasmids
      of the IncP-1 group, on the other hand, have autogenous control circuits, which
      allow a burst of expression during establishment in a new host, but a minimum of
      expression during maintenance. The lessons that plasmids have for clustering and
      co-regulation may explain the logic and organization of many small bacterial
      genomes currently being investigated.

PMID- 10931343
TI  - Plasmid copy number control: an ever-growing story.
AB  - Bacterial plasmids maintain their number of copies by negative regulatory systems
      that adjust the rate of replication per plasmid copy in response to fluctuations
      in the copy number. Three general classes of regulatory mechanisms have been
      studied in depth, namely those that involve directly repeated sequences
      (iterons), those that use only antisense RNAs and those that use a mechanism
      involving an antisense RNA in combination with a protein. The first class of
      control mechanism will not be discussed here. Within the second class (the most
      'classical' one), exciting insights have been obtained on the molecular basis of
      the inhibition mechanism that prevents the formation of a long-range RNA
      structure (pseudoknot), which is an example of an elegant solution reached by
      some replicons to control their copy number. Among the third class, it is
      possible to distinguish between (i) cases in which proteins play an auxiliary
      role; and (ii) cases in which transcriptional repressor proteins play a real
      regulatory role. This latter type of regulation is relatively new and seems to be
      widespread among plasmids from Gram-positive bacteria, at least for the rolling
      circle-replicating plasmids of the pMV158 family and the theta-replicating
      plasmids of the Inc18 streptococcal family.

PMID- 10931344
TI  - Phase variation of a beta-1,3 galactosyltransferase involved in generation of the
      ganglioside GM1-like lipo-oligosaccharide of Campylobacter jejuni.
AB  - Ganglioside mimicry by Campylobacter jejuni lipo-oligosaccharide (LOS) is thought
      to be a critical factor in the triggering of the Guillain-Barre and Miller-Fisher
      syndrome neuropathies after C. jejuni infection. The combination of a completed
      genome sequence and a ganglioside GM1-like LOS structure makes C. jejuni NCTC
      11168 a useful model strain for the identification and characterization of the
      genes involved in the biosynthesis of ganglioside-mimicking LOS. Genome analysis
      identified a putative LOS biosynthetic cluster and, from this, we describe a
      putative gene (ORF Cj1139c), which we have termed wlaN, with a significant level
      of similarity to a number of bacterial glycosyltransferases. Mutation of this
      gene in C. jejuni NCTC 11168 resulted in a LOS molecule of increased
      electrophoretic mobility, which also failed to bind cholera toxin. Comparison of
      LOS structural data from wild type and the mutant strain indicated lack of a
      terminal beta-1,3-linked galactose residue in the latter. The wlaN gene product
      was demonstrated unambiguously as a beta-1,3 galactosyltransferase responsible
      for converting GM2-like LOS structures to GM1-like by in vitro expression. We
      also show that the presence of an intragenic homopolymeric tract renders the
      expression of a functional wlaN gene product phase variable, resulting in
      distinct C. jejuni NCTC 11168 cell populations with alternate GM1 or GM2
      ganglioside-mimicking LOS structures. The distribution of wlaN among a number of
      C. jejuni strains with known LOS structure was determined and, for C. jejuni NCTC
      12500, similar wlaN gene phase variation was shown to occur, so that this strain
      has the potential to synthesize a GM1-like LOS structure as well as the
      ganglioside GM2-like LOS structure proposed in the literature.

PMID- 10931345
TI  - The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required
      for antiphagocytic function and virulence.
AB  - A variety of pathogenic bacteria use type III secretion pathways to translocate
      virulence proteins into host eukaryotic cells. YopE is an important virulence
      factor that is translocated into mammalian cells via a plasmid-encoded type III
      system in Yersinia spp. YopE action in mammalian cells promotes the disruption of
      actin filaments, cell rounding and blockage of phagocytosis. It was reported
      recently that two proteins with sequence similarity to YopE, SptP of Salmonella
      typhimurium and ExoS of Pseudomonas aeruginosa, function as GTPase-activating
      proteins (GAPs) for Rho GTPases. YopE contains an 'arginine finger' motif that is
      present in SptP, ExoS and other Rho GAPs and is essential for catalysis by this
      class of proteins. We show here that a GST-YopE fusion protein stimulated in
      vitro GTP hydrolysis by the Rho family members Cdc42, RhoA and Rac1, but not by
      Ras. Conversion of the essential arginine in the arginine finger motif to alanine
      (R144A) eliminated the in vitro GAP activity of GST-YopE. Infection assays
      carried out with a Yersinia pseudotuberculosis strain producing YopER144A
      demonstrated that GAP function was essential for the disruption of actin
      filaments, cell rounding and inhibition of phagocytosis by YopE in HeLa cells.
      Furthermore, the GAP function of YopE was important for Y. pseudotuberculosis
      pathogenesis in a mouse infection assay. Transfection of HeLa cells with a vector
      that produces a constitutively active form of RhoA (RhoA-V14) prevented the
      disruption of actin filaments and cell rounding by YopE. Production of an
      activated form of Rac1 (Rac1-V12), but not RhoA-V14, in HeLa cells interfered
      with YopE antiphagocytic activity. These results demonstrate that YopE functions
      as a RhoGAP to downregulate multiple Rho GTPases, leading to the disruption of
      actin filaments and inhibition of bacterial uptake into host cells.

PMID- 10931346
TI  - The partition system of multidrug resistance plasmid TP228 includes a novel
      protein that epitomizes an evolutionarily distinct subgroup of the ParA
      superfamily.
AB  - The segregational stability of bacterial, low-copy-number plasmids is promoted
      primarily by active partition. The plasmid-specified components of the
      prototypical P1 plasmid partition system consist of two proteins, ParA (44.3 kDa)
      and ParB (38.5 kDa), which, in conjunction with integration host factor, form a
      nucleoprotein complex at the plasmid partition site, parS. This complex is the
      probable substrate for the directed temporal and spatial intracellular movement
      of plasmids before cell division. The genetic organization of the partition
      cassette of the multidrug resistance plasmid TP228 differs markedly from that of
      the P1 paradigm. The TP228 system includes a novel member (ParF; 22.0 kDa) of the
      ParA superfamily of ATPases, of which the P1 ParA protein is the archetype.
      However, the ParF protein and its immediate relatives form a discrete subgroup of
      the ParA superfamily, which evolutionarily is more related to the MinD subgroup
      of cell division proteins than to ParA of P1. The TP228 and P1 partition modules
      differ further in that the former does not include a parB homologue, but does
      specify a protein (ParG; 8.6 kDa) unrelated to ParB. Homologues of the parF gene
      are widely disseminated on eubacterial genomes, suggesting that ParF-mediated
      partition may be a common mechanism by which plasmid segregational stability is
      achieved.

PMID- 10931347
TI  - Entamoeba histolytica cysteine proteinases with interleukin-1 beta converting
      enzyme (ICE) activity cause intestinal inflammation and tissue damage in
      amoebiasis.
AB  - The protozoan parasite Entamoeba histolytica causes intestinal inflammation and
      ulceration. Amoebic trophozoites activate the transcription factor NF-kappa B in
      human intestinal epithelial cells, initiating an inflammatory response programme
      with resultant damage to the intestinal tissue. Amoebic cysteine proteinases have
      been proposed as important virulence factors for amoebiasis. To test the role of
      amoebic cysteine proteinases in the pathogenesis of amoebic colitis, human
      intestinal xenografts in SCID mice were infected with E. histolytica trophozoites
      expressing an antisense message to ehcp5. The cysteine proteinase-deficient
      amoeba failed to induce intestinal epithelial cell production of the inflammatory
      cytokines interleukin (IL)-1B and IL-8, and caused significantly less gut
      inflammation and damage to the intestinal permeability barrier. The critical role
      of amoebic cysteine proteinases in human gut inflammation and tissue damage may
      be explained by our discovery that amoebic cysteine proteinases possess IL-1B
      converting enzyme (ICE) activity. This ICE activity could contribute to
      intestinal inflammation by activating human pIL-1B released by damaged intestinal
      cells. These results demonstrate for the first time that amoebic cysteine
      proteinases are a key virulence factor in amoebic colitis, and provide a novel
      mechanism for their activity.

PMID- 10931348
TI  - Evidence for a second function for Saccharomyces cerevisiae Rev1p.
AB  - The function of the Saccharomyces cerevisiae REV1 gene is required for
      translesion replication and mutagenesis induced by a wide variety of DNA-damaging
      agents. We showed previously that Rev1p possesses a deoxycytidyl transferase
      activity, which incorporates dCMP opposite abasic sites in the DNA template, and
      that dCMP insertion is the major event during bypass of an abasic site in vivo.
      However, we now find that Rev1p function is needed for the bypass of a T-T (6-4)
      UV photoproduct, a process in which dCMP incorporation occurs only very rarely,
      indicating that Rev1p possesses a second function. In addition, we find that
      Rev1p function is, as expected, required for bypass of an abasic site. However,
      replication past this lesion was also much reduced in the G-193R rev1-1 mutant,
      which we find retains substantial levels of deoxycytidyl transferase activity.
      This mutant is, therefore, presumably deficient principally in the second, at
      present poorly defined, function. The bypass of an abasic site and T-T (6-4)
      lesion also depended on REV3 function, but neither it nor REV1 was required for
      replication past the T-T dimer; bypass of this lesion presumably depends on
      another enzyme.

PMID- 10931349
TI  - The DNA binding and pairing preferences of the archaeal RadA protein demonstrate
      a universal characteristic of DNA strand exchange proteins.
AB  - The archaeal RadA protein is a homologue of the Escherichia coli RecA and
      Saccharomyces cerevisiae Rad51 proteins and possesses the same biochemical
      activities. Here, using in vitro selection, we show that the Sulfolobus
      solfataricus RadA protein displays the same preference as its homologues for
      binding to DNA sequences that are rich in G residues, and under-represented in A
      and C residues. The RadA protein also displays enhanced pairing activity with
      these in vitro-selected sequences. These parallels between the archaeal, eukaryal
      and bacterial proteins further extend the universal characteristics of DNA strand
      exchange proteins.

PMID- 10931350
TI  - Characterization of the 2-ketogluconate utilization operon in Pseudomonas
      aeruginosa PAO1.
AB  - The Pseudomonas aeruginosa protein PtxS negatively regulates its own synthesis by
      binding to the upstream region of its gene. We have recently identified a 14 bp
      palindromic sequence within the ptxS upstream region as the PtxS operator site
      (OP1). In this study, we searched the P. aeruginosa genomic sequence to determine
      whether this 14 bp sequence exists in other regions of the P. aeruginosa
      chromosome. Another PtxS operator site (OP2) was located 47 bp downstream of
      ptxS. DNA gel shift experiments confirmed that PtxS specifically binds to a 520
      bp fragment that carries OP2. The DNA segment 3' of OP2 contains four open
      reading frames (ORF1-ORF4), which code for 29, 32, 48 and 35 kDa proteins
      respectively. The molecular weight of the products of ORFs 2 and 3 were confirmed
      by T7 expression experiments. Computer analyses suggest that ORF2 encodes an ATP
      dependent kinase; ORF3, a transporter; and ORF4, a dehydrogenase. The predicted
      product of ORF1 showed no homology to previously identified proteins and contains
      all the conserved amino acids within the aldose 1-epimerase protein motif.
      Examination of the ptxs-ORF1 intergenic region (using promoter fusion
      experiments) showed that no potential promoter exists. An isogenic mutant
      defective in ORF1 was constructed in the P. aeruginosa strain PAO1. In contrast
      to its parent strain, the mutant failed to grow on a minimal medium in which 2
      ketogluconate was the sole carbon source. Similarly, a previously constructed
      ptxS isogenic mutant of PAO1 did not grow in a minimal medium containing 2
      ketogluconate as the sole carbon source. Furthermore, a plasmid carrying a
      fragment that contains ptxS and ORFs 1-4 complemented the defect of the
      previously described P. aeruginosa 2-ketogluconate-negative mutant. In the
      presence of 10 mM 2-ketogluconate, the in vitro binding of PtxS to a DNA fragment
      that carries either OP1 or OP2 was inhibited. These results suggest that: (i)
      ptxS together with the other four ORFs constitute the 2-ketogluconate utilization
      operon (kgu) in P. aeruginosa. Therefore, ORFs 1-4 were designated kguE, kguK,
      kguT and kguD respectively. (ii) PtxS regulates the expression of the kgu operon
      by binding to two operators (OP1 and OP2) within the operon; and (iii) 2
      ketogluconate is the molecular inducer of the kgu operon or the molecular
      effector of PtxS.

PMID- 10931351
TI  - Targeted disruption of the glycosylphosphatidylinositol-anchored surface antigen
      SAG3 gene in Toxoplasma gondii decreases host cell adhesion and drastically
      reduces virulence in mice.
AB  - The protozoan parasite Toxoplasma gondii is able to invade a broad range of cells
      within its mammalian hosts through mechanisms that are not yet fully understood.
      Several glycosylphosphatidylinositol-anchored antigens found in the parasite
      membrane are considered as major determinants in the critical interactions with
      the host cell. We have discovered that two of these surface antigens, SAG1 and
      SAG3, share significant identity, with considerable similarities in structure,
      suggesting an overall conserved topology. To investigate their physiological
      roles further, we have generated T. gondii mutants deficient in SAG3 through gene
      disruption. The disrupted strains display at least a twofold reduction in host
      cell invasion when compared with wild-type parasites. This correlated with a
      similar decrease in host cell adhesion in the SAG3 null mutants. Importantly, the
      null SAG3 mutants show attenuated infectivity, with a markedly reduced capacity
      to cause mortality in mice, whereas both wild-type and complemented mutants that
      re-expressed SAG3 were lethal at the same doses. Taken together, our results
      indicate that SAG3 is one member of the redundant system of T. gondii receptors
      that act as ligands mediating host cell recognition and attachment.

PMID- 10931352
TI  - Activation and silencing of leu-500 promoter by transcription-induced DNA
      supercoiling in the Salmonella chromosome.
AB  - The notion that transcription can generate supercoils in the DNA template largely
      stems from work with small circular plasmids. In the present work, we tested this
      model in the bacterial chromosome using a supercoiling-sensitive promoter as a
      functional sensor of superhelicity changes. The leu-500 promoter of Salmonella
      typhimurium is a mutant and inactive variant of the leucine operon promoter that
      regains activity if negative DNA supercoiling rises above normal levels,
      typically as a result of mutations affecting DNA topoisomerase I (topA mutants).
      Activation of the leu-500 promoter was analysed in topA mutant cells harbouring
      transcriptionally inducible tet or cat gene cassettes inserted in the region
      upstream from the leu operon. Some insertions inhibited leu-500 promoter
      activation in the absence of inducer. This effect is dramatic in the interval
      between 1.7 kb and 0.6 kb from the leu operon, suggesting that the insertions
      physically interfere with the mechanism responsible for activation. Superimposed
      on these effects, transcription of the inserted gene stimulated or inhibited leu
      500 promoter activity depending on whether this gene was oriented divergently
      from the leu operon or in the same direction respectively. Interestingly,
      transcription-mediated inhibition of leu-500 promoter was observed with inserts
      as far as 5 kb from the leu operon, and it could be relieved by the introduction
      of a strong gyrase site between the inserted element and the leu-500 promoter.
      These results are consistent with the idea that transcriptionally generated
      positive and negative supercoils can diffuse along chromosomal DNA and, depending
      on their topological sign, elicit opposite responses from the leu-500 promoter.

PMID- 10931353
TI  - Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in
      constitutive weak organic acid resistance, associated with a post-transcriptional
      activation of the Pdr12 ATP-binding cassette transporter.
AB  - Yeast cells display an adaptive stress response when exposed to weak organic
      acids at low pH. This adaptation is important in the spoilage of preserved foods,
      as it allows growth in the presence of weak acid food preservatives. In
      Saccharomyces cerevisiae, this stress response leads to strong induction of the
      Pdr12 ATP-binding cassette (ABC) transporter, which catalyses the active efflux
      of weak acid anions from the cytosol of adapted cells. S. cerevisiae cells
      lacking the Cmk1 isoform of Ca2+-calmodulin-dependent protein kinase are
      intrinsically resistant to weak acid stress, in that they do not need to spend a
      long adaptive period in lag phase before resuming growth after exposure to this
      stress. This resistance of the cmk1 mutant is Pdr12 dependent and, unlike with
      wild-type S. cerevisiae, cmk1 cells are capable of performing Pdr12-specific
      functions such as energy-dependent cellular extrusion of fluorescein and
      benzoate. However, they have neither higher PDR12 gene promoter activity nor
      higher Pdr12 protein levels. The increased Pdr12 activity in cmk1 cells is
      therefore caused by Cmk1 exerting a negative post-transcriptional influence over
      the activity of the Pdr12 ABC transporter, a transporter protein that is
      constitutively expressed in low-pH yeast cultures. This is the first preliminary
      evidence that shows a protein kinase, either directly or indirectly, regulating
      the activity of a yeast ABC transporter.

PMID- 10931354
TI  - A temperature-sensitive Krp1 allows in vivo characterization of kexin activation.
AB  - Members of the kexin family of processing enzymes are responsible for the
      cleavage of many proproteins during their transport through the secretory
      pathway. The enzymes are themselves made as inactive precursors and we have
      investigated the activation of Krp1, a kexin from the fission yeast
      Schizosaccharomyces pombe. As Krp1 is essential for cell growth, we have used a
      krp1ts strain to investigate the role of the prosequence in the activation
      process. Mutations that reduce either the efficiency with which the prosequence
      is released or the rate at which the released prosegment is subsequently cleaved
      at an internal site are less active when assayed in vivo. We also show that
      prosegments lacking an internal dibasic motif can act as autoinhibitors and
      prevent activation of the catalytic fragment. Krp1 constructs containing
      prosequences based on these inhibitors do not become active in vitro.
      Surprisingly, the same constructs do become active in the intact cell and appear
      to suggest that alternative activation processes can be used by these enzymes.

PMID- 10931355
TI  - Functional analysis of promoters involved in quorum sensing-based regulation of
      bacteriocin production in Lactobacillus.
AB  - Bacteriocin production in Lactobacillus sake LTH673 involves at least four
      operons: a regulatory operon (sppIPKR); two operons encoding bacteriocins and
      their immunity proteins (sppAiA and orfX); and an operon needed for secretion
      (sppTE). We show here that the response regulator encoded by sppR in L. sake
      LTH673, as well as the homologous response regulators encoded by plnC and plnD in
      Lactobacillus plantarum C11, bind to characteristic repeats found in the -80 to 
      40 regions of spp operons. The promoters controlling bacteriocin operons are
      strictly regulated, and their activity is increased more than 1000-fold upon
      activation. Constitutive expression for the regulatory and transport operons is
      driven, at least in part, by promoters upstream of the -80 to -40 regions. Peak
      promoter activity of the regulatory and transporter operons precedes that of the
      two bacteriocin operons. The results reveal how promoters involved in quorum
      sensing-based regulation of bacteriocin production in Lactobacillus differ in
      strength, leakiness and timing of their activity.

PMID- 10931356
TI  - The Escherichia coli SeqA protein destabilizes mutant DnaA204 protein.
AB  - In wild-type Escherichia coli cells, initiation of DNA replication is tightly
      coupled to cell growth. In slowly growing dnaA204 (Ts) mutant cells, the cell
      mass at initiation and its variability is increased two- to threefold relative to
      wild type. Here, we show that the DnaA protein concentration was two- to
      threefold lower in the dnaA204 mutant compared with the wild-type strain. The
      reason for the DnaA protein deficiency was found to be a rapid degradation of the
      mutant protein. Absence of SeqA protein stabilized the DnaA204 protein, increased
      the DnaA protein concentration and normalized the initiation mass in the dnaA204
      mutant cells. During rapid growth, the dnaA204 mutant displayed cell cycle
      parameters similar to wild-type cells as well as a normal DnaA protein
      concentration, even though the DnaA204 protein was highly unstable. Apparently,
      the increased DnaA protein synthesis compensated for the protein degradation
      under these growth conditions, in which the doubling time was of the same order
      of magnitude as the half-life of the protein. Our results suggest that the
      DnaA204 protein has essentially wild-type activity at permissive temperature but,
      as a result of instability, the protein is present at lower concentration under
      certain growth conditions. The basis for the stabilization in the absence of SeqA
      is not known. We suggest that the formation of stable DnaA-DNA complexes is
      enhanced in the absence of SeqA, thereby protecting the DnaA protein from
      degradation.

PMID- 10931357
TI  - Regulation of intron function: efficient splicing in vivo of a bacterial group II
      intron requires a functional promoter within the intron.
AB  - Conjugative transfer of the Lactococcus lactis plasmid pRS01 requires splicing of
      a group II intron, Ll.ltrB, for accurate translation of the mRNA for the exon
      gene ltrB. The protein product of ltrB is a conjugative relaxase, essential for
      pRS01 transfer. Using a molecular technique for the identification of
      transcription initiation sites in bacteria, a functional promoter within Ll.ltrB
      was identified upstream from the gene for the intron-encoded protein (IEP) LtrA.
      LtrA is required for efficient splicing of Ll.ltrB in vivo. Mutation of the ltrA
      promoter dramatically reduced the steady-state level of ltrA mRNA, LtrA, intron
      splicing and conjugation in L. lactis. These effects could be relieved by
      expression in trans of the ltrA gene cloned under the control of an inducible
      promoter. These results suggest that the ltrA mRNAs are translated inefficiently.
      We hypothesize that this bacterial intron, in contrast to previously studied
      group II introns in eukaryotes, requires a promoter within the intron to regulate
      ltrA expression and to produce an adequate level of the protein in the cell for
      efficient splicing.

PMID- 10931358
TI  - The antisense RNA of the par locus of pAD1 regulates the expression of a 33-amino
      acid toxic peptide by an unusual mechanism.
AB  - The par stability determinant of the Enterococcus faecalis plasmid pAD1 is the
      first antisense RNA-regulated post-segregational killing system (PSK) identified
      in a Gram-positive organism. Par encodes two small, convergently transcribed
      RNAs, designated RNA I and RNA II, which are the toxin and antidote of the par
      PSK system respectively. RNA I encodes an open reading frame of 33 codons
      designated fst. The results presented here demonstrate that the peptide encoded
      by fst is the par toxin. The fst sequence was shown to be sufficient for cell
      killing, and removal of the final codon inactivated the toxin. In vitro
      translation reactions of purified RNA I transcript produced a product of the
      expected size for the fst-encoded peptide. This product was not produced when
      purified RNA II transcript was added to the translation reaction. Toeprint
      analysis demonstrated that purified RNA II was able to inhibit ribosome binding
      to RNA I. These data suggest that fst expression is regulated by RNA II via an
      antisense RNA mechanism. In vitro translation studies and toeprint analyses also
      indicated that fst expression is internally regulated by a stem-loop structure at
      the 5' end of RNA I. Removal of this structure resulted in better ribosome
      binding to RNA I and a 300-fold increase in production of the fst-encoded
      peptide. Finally, RNA II was shown to be less stable than RNA I in vivo,
      providing a basis for the selective expression of fst in plasmid-free cells.

PMID- 10931359
TI  - Antisense RNA regulation of the pAD1 par post-segregational killing system
      requires interaction at the 5' and 3' ends of the RNAs.
AB  - The par stability determinant of the Enterococcus faecalis plasmid pAD1 is the
      first antisense RNA-regulated post-segregational killing system (PSK) identified
      in a Gram-positive organism. Par encodes two small, convergently transcribed
      RNAs, designated RNA I and RNA II, which are the toxin and antidote of the par
      PSK system respectively. RNA I encodes an open reading frame for a 33-amino-acid
      toxin called Fst. Expression of fst is regulated post-transcriptionally by RNA
      II. In this paper, RNA II is shown to interact with RNA I by a unique antisense
      RNA mechanism. RNA I and RNA II contain complementary direct repeats at their 5'
      ends and a complementary transcriptional terminator stem-loop at their 3' ends.
      Deletion of the terminator or mutations within the terminator loop of RNA II
      severely reduced the rate of interaction in vitro. Mutations in the 5' direct
      repeats of RNA II prevented the RNAs from interacting in vitro. For these
      mutations in RNA II, complementary mutations in RNA I were shown to restore
      interaction. The reduced binding efficiency of the RNA II mutants was paralleled
      by the failure of these mutants to suppress par-mediated killing in vivo. These
      results indicate that regions at both the 5' and the 3' ends of the par
      transcripts are important for RNA I-RNA II interaction.

PMID- 10931360
TI  - Individual functions of the HAK and TRK potassium transporters of Schwanniomyces
      occidentalis.
AB  - We have cloned the gene encoding the TRK transporter of the soil yeast
      Schwanniomyces occidentalis and obtained the HAK1 trk1 delta and the hak1 delta
      TRK1 mutant strains. Analyses of the transport capacities of these mutants have
      shown that (i) the HAK1 and the TRK1 potassium transporters are the only
      transporters operating at low and medium K+ concentrations (< 1 mM); (ii) the
      HAK1 transporter is functional at low pH but fails at high pH; and (iii) the TRK1
      transporter functions at neutral and high pH and fails at low pH. At neutral pH,
      both transporters are functional, but HAK1 is not expressed, except at very low
      K+ concentrations (< 50 microM) where HAK1 is very effective. TRK1 is also
      involved in the control of the membrane potential.

PMID- 10931362
TI  - Editorial

PMID- 10931361
TI  - Escherichia coli cells defective for the recN gene display constitutive elevation
      of mutagenesis at 3,N(4)-ethenocytosine via an SOS-induced mechanism.
AB  - The Escherichia coli UVM (UV Modulation of mutagenesis) response is a DNA damage
      inducible mutagenic pathway detected as significantly increased mutagenesis at
      3,N4-ethenocytosine (epsilon C) lesions borne on transfected single-stranded M13
      vector DNA. All major classes of DNA-damaging agents can induce UVM, and the
      phenomenon is independent of previously characterized mutagenic responses in E.
      coli. To understand this phenomenon further, we set out to identify and
      characterize mutants in the UVM response. Screening a mutant bank of cells
      defective for 1-methyl-3-nitro-1-nitrosoguanidine-inducible genes revealed that
      defects in the recN gene cause a constitutive elevation of mutagenesis at epsilon
      C residues. In contrast to normal cells that show approximately 6% mutagenesis at
      epsilon C lesions, but approximately 60% upon UVM induction, recN-defective
      strains display approximately 50% mutagenesis at epsilon C lesion sites in
      untreated cells. However, the recN-mediated mutagenesis response was found to
      require the recA gene and the umuDC genes, and could be suppressed in the
      presence of a plasmid harbouring the SOS transcriptional repressor LexA. These
      results imply that recN cells are constitutively active for SOS mutagenesis
      functions. The observation that epsilonC mutagenesis is enhanced in recN cells
      confirms previous findings that mutagenesis at epsilonC can also be independently
      elevated by the SOS pathway.

PMID- 10931363
TI  - Small heat shock proteins, the cytoskeleton, and inclusion body formation.
AB  - Since first being implicated in central nervous system disease 10 years ago, much
      has been learned concerning the regulation and function of the small heat shock
      protein alpha B-crystallin. Neuropathological, cellular and molecular studies all
      now point to a functional relationship between alpha B-crystallin and
      intermediate filaments. alpha B-crystallin accumulation marks reactive astrocytes
      in general in a wide variety of disorders and specifically intermediate filament
      based glial inclusion bodies such as Rosenthal fibres found in astrocytes in
      Alexander's disease. In vitro, alpha B-crystallin expression suppresses
      intermediate filament aggregation and can prevent or reverse experimentally
      induced glial inclusion body formation. Conversely, dysregulation of glial
      fibrillary acidic protein expression in vivo results in Rosenthal fibre formation
      and upregulation of endogenous alpha B-crystallin expression. These data and
      those from studies recently carried out on other tissues strongly suggest that
      one function of this small heat shock protein is to modulate intermediate
      filament organization under conditions of physiological stress and
      neurodegenerative disease.

PMID- 10931364
TI  - Emerging and re-emerging epidemic encephalitis: a tale of two viruses.
AB  - Two major epidemics of viral encephalitis occurred in Asia in 1997 and 1998. The
      first was a re-emergence of neurovirulent strains of enterovirus 71, which caused
      severe encephalomyelitis in children in Malaysia, Taiwan and Japan, on a
      background of hand, foot and mouth disease. Necropsy studies of patients who died
      of enterovirus 71 infection showed severe perivascular cuffing, parenchymal
      inflammation and neuronophagia in the spinal cord, brainstem and diencephalon,
      and in focal areas in the cerebellum and cerebrum. Although no viral inclusions
      were detected, immunohistochemistry showed viral antigen in the neuronal
      cytoplasm. Inflammation was often more extensive than neuronal infection,
      suggesting that other factors, in addition to direct viral cytolysis, may be
      involved in tissue damage. The second epidemic of viral encephalitis was the
      result of a novel paramyxovirus called Nipah, which mainly involved pig handlers
      in Malaysia and Singapore. Pathological evidence suggested that the endothelium
      of small blood vessels in the central nervous system was particularly susceptible
      to infection. This led to disseminated endothelial damage and syncytium
      formation, vasculitis, thrombosis, ischaemia and microinfarction. However, there
      was also evidence of neuronal infection by the virus and this may also have
      contributed to the neurological dysfunction in Nipah encephalitis. Some patients
      who seemed to recover from the acute symptoms have been re-admitted with clinical
      findings suggestive of relapsing encephalitis. As these two epidemics indicate,
      the emergence and re-emergence of viral encephalitides continue to pose
      considerable challenges to the neuropathologist, in establishing the diagnosis
      and unravelling the pathogenesis of the neurological disease.

PMID- 10931365
TI  - Grading of diffusely infiltrating astrocytomas by quantitative histopathology,
      cell proliferation and image cytometric DNA analysis. Comparison of 133 tumours
      in the context of the WHO 1979 and WHO 1993 grading schemes.
AB  - The aim of the study was to evaluate the applicability of quantitative
      histopathology as an aid for grading diffusely infiltrating astrocytomas. Primary
      astrocytomas were analysed for parameters (mean nuclear size, mitosis count, area
      fraction of endothelial cells and tumour necrosis, area fraction of nuclei, and
      Ki-67 (MIB-1) labelling index), which are closely related to the World Health
      Organization (WHO) 1979 and WHO 1993 grading criteria. All estimates correlated
      with the WHO histopathological grade and patient outcome. According to the
      receiver-operating characteristics curve, the presence of tumour necrosis and
      mitosis count (cut-off at 3 mitoses/mm2 of neoplastic tissue) showed the best
      sensitivity and specificity in separating patients with different survival. The
      multivariate survival analyses confirmed this result. A decision-tree model was
      constructed based on these two variables: twig I with less than 3 mitoses/mm2,
      twig II with equal or more than 3 mitoses/mm2 but no necrosis, and twig III with
      tumour necrosis. This model was found to be more strongly associated with
      survival than the WHO 1979 or WHO 1993 grading schemes. Low-malignancy
      astrocytomas (WHO grade II or twig I tumours) could be further divided into two
      prognostic categories by the image cytometric DNA analysis. The results put an
      emphasis on astrocytoma grading on mitosis counts (grade II vs. III) and tumour
      necrosis (grade III vs. IV). To standardize the sampling for mitosis counting, it
      is suggested that a parallel Ki-67 immunostaining be used for the identification
      of the most proliferative areas.

PMID- 10931366
TI  - Differential expression of intercellular adhesion molecule-1 and vascular cell
      adhesion molecule-1 in chronic murine retroviral encephalitis.
AB  - The cell adhesion molecules, intercellular adhesion molecule (ICAM)-1 and
      vascular cell adhesion molecule (VCAM)-1, are important mediators of immune
      interactions within the central nervous system (CNS). A wide variety of pro
      inflammatory insults to the brain, including viral infection, result in
      upregulation of these molecules on brain endothelial cells, astrocytes, and
      microglia. This study investigated the expression of ICAM-1 and VCAM-1 in chronic
      encephalitis induced by infection with a temperature sensitive (ts-1) strain of
      Moloney murine leukaemia virus (MoMuLV), an ecotropic murine retrovirus. During
      the late stages of disease, viral antigen was present in both endothelial cells
      and microglia, but not astrocytes, in regions of spongiform change and gliosis.
      In these areas, ICAM-1 staining was detected on activated microglia, but not on
      endothelial cells or astrocytes. In contrast, no cells showed increased VCAM-1
      expression in the CNS. These findings demonstrate that there is cell-specific,
      differential expression of these adhesion molecules in ts-1 retroviral
      encephalitis. The lack of endothelial cell expression correlates with the
      characteristic lack of lymphocytic infiltrate in this chronic retroviral
      encephalitis and suggests that increased microglial ICAM-1 expression may play a
      role in the pathogenesis of MoMuLV (ts-1)-mediated neurodegeneration.

PMID- 10931367
TI  - Caspase-cleaved actin (fractin) immunolabelling of Hirano bodies.
AB  - Hirano bodies are eosinophilic rod-like inclusions that are found predominantly
      in neuronal processes in the hippocampal CA1 sector with increasing age and are
      particularly numerous in Alzheimer's disease. They contain a variety of
      cytoskeletal epitopes, especially actin and actin-binding proteins. Actin
      cleavage by cysteinyl aspartate-specific proteases (caspases) is a feature of
      apoptosis. Cleavage at aspartate 244 generates N-terminal 32 kDa and C-terminal
      15 kDa actin fragments. This has led to the development of a rabbit polyclonal
      antibody specific for caspase-cleaved actin, directed to the last five C-terminal
      amino acids of the 32 kDa fragment of actin ('fractin'). Fractin
      immunohistochemistry was performed on hippocampal sections from Alzheimer's
      disease and control cases containing numerous Hirano bodies, in addition to
      immunolabelling with CM1 antiserum which recognizes activated caspase-3. The
      Hirano bodies showed strong diffuse fractin immunoreactivity. They did not label
      with CM1 antiserum, perhaps reflecting too low a level of activated caspase-3 for
      immunodetection, or involvement of a different member of the caspase family. The
      finding of fractin immunoreactivity of Hirano bodies suggests that caspase-like
      cleavage of actin may play a role in their formation and further supports caspase
      like activity in neuronal processes, distinct from that associated with acute
      perikaryal apoptosis.

PMID- 10931368
TI  - Immunocytochemical study of the dorsal and median raphe nuclei in patients with
      Alzheimer's disease prospectively assessed for behavioural changes.
AB  - The dorsal and median raphe nuclei were examined with immunocytochemistry to
      display the 5-HT neurones in 16 cases of post-mortem-proven Alzheimer's disease
      (AD) and 12 age and sex-matched controls. The AD cases had been prospectively
      assessed during life for expression of behavioural changes as well as for
      cognitive decline. A significant (P < 0.001) 41% reduction in density of dorsal
      raphe neurones was found along with a significant (P < 0.02) 29% reduction in
      density of median raphe neurones in AD. There were significantly more
      neurofibrillary tangles in both dorsal and median raphe nuclei in AD than in
      controls (P < 0.001). There was no correlation between reduction in neurone
      density in these nuclei and behavioural change, cognitive decline,
      neurofibrillary tangle counts in these nuclei or plaque and tangle pathology in
      frontal and temporal cortex. It was concluded from these findings that the raphe
      nuclei are significantly affected by the pathology of AD and that plasticity in
      the 5-HT system is the probable reason for the lack of correlation of reduced 5
      HT neurone density and clinical disease parameters.

PMID- 10931369
TI  - Monocyte infiltration is highly associated with loss of the tight junction
      protein zonula occludens in HIV-1-associated dementia.
AB  - In human immunodeficiency virus (HIV)-1-associated dementia (HAD), consequences
      of interactions between infiltrating monocytes and brain endothelial cells are
      not yet fully understood. This study investigated whether the blood-brain barrier
      is affected in brain tissue of patients suffering from HAD and whether it was
      possible to find a correlation with the presence or absence of monocytic cells,
      which have been suggested to play a major role in HAD. Immunohistochemical
      analysis for zonula occludens 1, a tight junction protein, and CD68, a macrophage
      marker, revealed that loss of tight junction immunoreactivity was highly
      correlated with monocyte infiltration and with HAD. This suggests that the
      presence of perivascular macrophages cells is associated with breakdown of the
      blood-brain barrier thereby facilitating infiltration of more monocytic cells
      hence enhancing disease progression.

PMID- 10931370
TI  - Loss of neurofibromatosis 1 (NF1) gene expression in NF1-associated pilocytic
      astrocytomas.
AB  - The critical role of the neurofibromatosis 1 (NF1) gene as a tumour suppressor
      has been clearly demonstrated for malignancies arising in NF1 patients. However,
      little is known about the more common benign tumours, such as the pilocytic
      astrocytoma. Most NF1-associated astrocytomas are benign and clinically non
      progressive, though aggressive tumours are occasionally encountered. In this
      study, eight pilocytic astrocytomas from six individuals affected with NF1 were
      analysed for NF1 expression. All eight tumours demonstrated loss of neurofibromin
      expression by immunohistochemistry, which was confirmed in one case using Western
      blot analysis. Microsatellite analysis showed loss of a single NF1 allele (LOH)
      in two of four NF1-associated tumours. These results demonstrate that, in
      contrast to sporadic astrocytomas, loss of NF1 expression is an important primary
      genetic event in the pathogenesis of NF1-associated pilocytic astrocytomas.

PMID- 10931371
TI  - A new case of frontotemporal dementia and parkinsonism resulting from an intron
      10 +3-splice site mutation in the tau gene: clinical and pathological features.
AB  - Hereditary frontotemporal dementia and parkinsonism (FTDP) linked to chromosome
      17 (FTDP-17) constitutes a new form of tauopathy, and mutations in the tau gene
      have recently been reported in some affected families. This report presents
      clinical and neuropathological data from a member of a British family (SOT 254)
      with a history of dementia and movement disorder. The medical history of the
      affected patient, a woman aged 44 years, was reviewed, and a detailed post-mortem
      examination of the brain was undertaken. A panel of well characterized
      phosphorylation-dependent and independent anti-tau antibodies was used to assess
      tau pathology, and inclusions were examined by electron microscopy. Neuronal loss
      and gliosis were widely distributed, but most severe in neocortical regions, and
      were associated with abundant neuronal and glial tau inclusions which consisted
      of a mixture of paired helical filaments (PHFs), similar to those in Alzheimer's
      disease, and distinct twisted ribbon-like filaments. Genomic DNA was obtained
      from post-mortem tissue from the index patient, and blood from two unaffected
      members of the same family. For the index case only, sequencing of intronic
      sequences flanking exon 10 of the tau gene identified a G to A transition at
      position +3 of the splice-donor site downstream of exon 10, identical to that
      reported in multiple system tauopathy with presenile dementia (MSTD). The
      clinical, neuropathological and genetic findings strongly suggest that SOT 254
      represents a new example of FTDP-17 resulting from a mutation in the tau gene.
      These results are compared with those reported for other FTDP-17 families, i.e.
      for MSTD.

PMID- 10931372
TI  - Vascular endothelial growth factor expression in oligodendrogliomas: a
      correlative study with Sainte-Anne malignancy grade, growth fraction and patient
      survival.
AB  - Microangiogenesis is a delayed but crucial event in the malignant progression of
      oligodendrogliomas. Accord-ingly, in the new Sainte-Anne grading system of
      oligodendrogliomas, endothelial hyperplasia and contrast enhancement, both being
      indicators of microangiogenesis, are key criteria for the distinction of grade A
      from grade B tumours. Vascular endothelial growth factor (VEGF) is a potent
      angiogenic factor: a strong correlation between VEGF expression, Sainte-Anne
      malignancy grade and patient outcome might thus be expected. In order to assess
      this hypothesis, VEGF immunostaining was performed in a series of 34
      oligodendrogliomas that included 11 grade B and 23 grade A, of which nine became
      grade B during the study period (mean clinical and imaging follow-up: 41 months).
      VEGF expression correlated strongly with Sainte-Anne tumour grade (P < 0.001),
      and inversely with patient survival (P < 0.001) and recurrence-free survival (P =
      0.002). One hundred per cent of grade B but only 17% of grade A were VEGF
      positive. By contrast, the MIB-1 labelling index did not correlate with VEGF
      expression, total survival or recurrence-free survival. In accordance with the
      grading system, this study showed that, in oligodendrogliomas, VEGF expression
      and microangiogenesis are progression-related phenomena that confer on these
      tumours a growth advantage by presumably reducing hypoxia-induced apoptotic cell
      death. These findings might have important implications in the future for the
      indication and timing of anti-angiogenic therapies.

PMID- 10931373
TI  - Phosphorylation of retinoblastoma protein in rat brain after transient middle
      cerebral artery occlusion.
AB  - Although mature neurones do not replicate genomic DNA, some cell cycle-related
      kinases are aberrantly activated in neurones after ischaemia. As hyper
      phosphorylation of retinoblastoma (Rb) protein is the common pathway in mitotic
      signal cascade, this study investigated the phosphorylation state of the Rb
      protein as well as its mRNA level in rat brain after transient middle cerebral
      artery (MCA) occlusion. Immunohisto-chemical analysis revealed that neurones in
      the sham-operated brain expressed Rb protein without the hyperphosphorylated
      form. Immunoreactivity for the hyperphosphorylated form of Rb protein
      progressively increased from 1 h to 3 days after ischaemia in neurones in the MCA
      territory. Western blot analysis demonstrated a similar change. However, reverse
      transcription-polymerase chain reaction study revealed that Rb showed no definite
      change at the mRNA level. These results suggest that Rb protein is progressively
      hyper-phosphorylated in the brain after ischaemia, which may activate apoptotic
      mechanisms in neuronal cells of the brain after ischaemia.

PMID- 10931374
TI  - An unusual case of familial amyotrophic lateral sclerosis with extensive
      involvement and neuronal cytoplasmic inclusions.

PMID- 10931375
TI  - Editorial

PMID- 10931376
TI  - Localization of human serum amyloid P component and heparan sulfate proteoglycan
      in in vitro-formed Abeta fibrils.
AB  - Ultrastructural studies of the localization of serum amyloid P component (SAP) in
      amyloid fibrils have given divergent results. We here report for the first time
      that electron microscopy of SAP coincubated with Abeta1-42 peptides or with
      mature Abeta1-42 fibrils, revealed SAP molecules coating the surface of the
      mature fibrils and that protofibrils of Abeta1-42 did not bind SAP. Also when
      incubated with extracted amyloid light chain (AL)-fibrils the SAP molecules
      aligned on the fibril surface. Heparan sulfate proteoglycan bound to the surface
      of the Abeta fibrils with a spacing of about 50 nm. We conclude that SAP does not
      bind to protofibrils but to the surface of mature Abeta fibrils and that it may
      stabilize and protect the fibrils.

PMID- 10931377
TI  - P64k meningococcal protein as immunological carrier for weak immunogens.
AB  - Previously, the P64k meningococcal protein, an antigen of 64 kDa expressed in
      Escherichia coli, has been extensively characterized. We have successfully
      conjugated several synthetic peptides and meningococcal group C polysaccharide to
      P64k. In three out of four model peptides, the murine humoral immune response
      against the homologous peptide, evaluated after three doses of conjugate, was
      higher in the animals immunized with the coupled peptide than in those that
      received free peptide. The fourth and largest was immunogenic by itself.
      Similarly, the antigroup C polysaccharide levels reached by conjugated
      polysaccharide were significantly higher than those produced against unconjugated
      polysaccharide. As a carrier for one of the peptides, P64k was compared with
      bovine serum albumin (BSA) and tetanus toxoid (TT), being able to induce slightly
      higher or similar antipeptide antibody levels than these well-establish protein
      carriers. Our results suggest that recombinant P64k protein could be a readily
      available immunological carrier, as efficient as other commonly used large
      carrier molecules.

PMID- 10931378
TI  - Augmented expression of daintain/allograft inflammatory factor-1 is associated
      with clinical disease: dynamics of daintain/allograft inflammatory factor-1
      expression in spleen, peripheral nerves and sera during experimental autoimmune
      neuritis.
AB  - Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barre
      syndrome, characterized by inflammation and demyelination of the peripheral
      nervous system (PNS). Daintain/allograft inflammatory factor-1 (daintain/AIF-1)
      is a novel interferon-gamma-inducible protein expressed by macrophages during
      organ specific autoimmune diseases. To study the involvement of daintain/AIF-1 in
      EAN we induced EAN in Lewis rats by immunizing with bovine PNS myelin (BPM) and
      complete Freund's adjuvant (CFA). The expression of daintain/AIF-1 was examined
      in the spleen, peripheral nerves and sera during the course of EAN by
      immunohistochemistry and radioimunoassay (RIA). The expression of daintain/AIF-1
      in the spleen and in the sciatic nerves peaked at the preclinical stage (day 7
      post immunization (p.i.)) and at the height (day 15 p.i.) of clinical EAN,
      consistent with a disease promoting role for daintain/AIF-1. Daintain/AIF-1
      expressing cells represented a subset of ED1+ or CD11b/c+ mononuclear cells. A
      significant increase of daintain/AIF-1-like immunoreactivity in sera occurred at
      the preclinical stage of EAN. Taken together, these data indicate that
      daintain/AIF-1 may play a proinflammatory role in the pathogenesis of EAN.

PMID- 10931379
TI  - T-lymphocyte subpopulations do not express identical combinations of interleukin
      2 receptor chains in the early phase of their activation and proliferation.
AB  - Owing to the contrasting observations in the field of interleukin(IL)-2 receptor
      research, the expression of IL-2 receptor chains was analysed on resting and anti
      CD3 antibody (OKT3) activated CD4 and CD8 T cells by flow cytometry. Prior to the
      stimulation, 49% of CD4+ cells expressed IL-2Ralpha (CD25), whereas the
      expression of IL-2Rbeta (CD122) was very low (8%). The reverse was true for CD8
      cells: 48% of them were positive for CD122, but only a fraction (10%) expressed
      CD25. Practically all lymphocytes expressed IL-2Rgamma (CD132). Interestingly,
      the unbalanced expression of IL-2Ralpha and -beta continued throughout the
      stimulation period of 2 days. In addition, the expression of CD45 isoforms in
      combination with the IL-2R chains and CD71 was followed during the activation of
      CD4+ T cells. Although CD45RA+/RO- CD4 cells were effectively activated, they
      retained their naive phenotype up to 2 days of stimulation. On the other hand,
      CD45RA+low/RO+low (Ddull) CD4+ cells shifted to the memory phenotype rapidly
      after being activated. However, by day 6 of stimulation the shift of both naive
      and Ddull cells to memory ones was obvious. The role of the IL-2 receptor in the
      activation of CD4 subpopulations is discussed.

PMID- 10931380
TI  - A soluble mannose receptor immunoadhesin enhances phagocytosis of Pneumocystis
      carinii by human polymorphonuclear leukocytes in vitro.
AB  - Pneumocystis carinii is an opportunistic pathogen that causes pneumonia in
      immunocompromised hosts. In the normal host, P. carinii is susceptible to an
      array of first line host defense mechanisms that are operative in the lung.
      Alveolar macrophages play a central role in the clearance of inhaled organisms.
      The macrophage mannose receptor (MR) appears to be sufficient for P. carinii
      phagocytosis. In individuals infected with the human immunodeficiency virus, MR
      expression on alveolar macrophages and P. carinii phagocytosis are decreased,
      however, Fc-receptor mediated phagocytosis remains intact. In this study, we
      demonstrate that a recombinant soluble MR immunoadhesin, consisting of the
      essential carbohydrate binding MR ectodomain and the Fc-region of human
      immunoglobulin (Ig)G1, binds P. carinii and leads to an 8.2-fold increased uptake
      of P. carinii by phagocytic cells. Our results suggest that the soluble MR
      immunoadhesin may have therapeutic potential in the treatment of P. carinii
      infections.

PMID- 10931381
TI  - Characterization of murine dendritic cells derived from adherent blood
      mononuclear cells in vitro.
AB  - The therapeutic potential of dendritic cells loaded with tumour antigens for the
      induction of effective immune responses against cancer is currently being tested
      in numerous clinical trials. In most cases, the dendritic cells are generated in
      vitro from peripheral blood monocytes. Many aspects of dendritic cell-based
      vaccination have not yet been examined in detail, and homologous mouse model
      systems may prove very valuable for optimizing clinical procedures. In the murine
      system, however, dendritic cells are usually isolated from either lymphoid
      tissues or bone marrow cultures. To date, murine monocyte-derived dendritic cells
      have been described only sporadically. Here, we describe a culture system for the
      generation of murine dendritic cells from adherent peripheral blood mononuclear
      cells by culturing in the presence of granulocyte-macrophage colony stimulating
      factor and interleukin-4. After 7 days of culture the nonadherent cells were
      harvested from the cultures. Most of these cells exhibited well-accepted
      characteristics of mature dendritic cells (e.g. veiled appearance, high
      expression of major histocompatibility complex class II and CD86) and stimulated
      vigorous proliferation of allogeneic T cells in a primary mixed leucocyte
      reaction following stimulation with bacterial lipopolysaccharide. Interestingly,
      staining the cells for expression of the putative antigen-uptake receptor DEC-205
      revealed a distinct bimodal distribution.

PMID- 10931382
TI  - Interleukin-2-induced nitric oxide synthase and nuclear factor-kappaB activity in
      activated natural killer cells and the production of interferon-gamma.
AB  - We have previously shown that inducible nitric oxide synthase (iNOS) was up
      regulated in natural killer (NK) cells when AK-5 tumour cells were transplanted
      subcutaneously into syngeneic Wistar rats. This study was designed to investigate
      the role of interleukin (IL)-2 during the induction of iNOS and to understand the
      subsequent events involved in NK cell activation. There was up-regulation of iNOS
      expression when naive NK cells were cultured in the presence of recombinant IL-2.
      These NK cells produced a higher nitrite content and possessed cytotoxic activity
      against YAC-1 and AK-5 tumour cells. Induction of iNOS enhanced nuclear factor
      (NF)-kappaB binding activity in IL-2 activated NK cells, which was confirmed
      using L-NAME, an NO synthesis inhibitor. Addition of L-NAME along with rIL-2
      significantly blocked NF-kappaB activity and also down-regulated the production
      of NO and the cytotoxic activity of NK cells. Furthermore, injection of anti-IL-2
      antibody in subcutaneous tumour transplanted animals abrogated significantly the
      expression of iNOS and NF-kappaB activity, leading to reduced NO production and
      cytotoxic activity of NK cells against YAC-1 and AK-5 cells. In addition, the
      expression of interferon (IFN)-gamma by NK cells was also inhibited in anti-IL-2
      antibody injected animals compared with the control animals. Finally, there was
      enhanced tumour growth and delayed regression in anti-IL-2 injected animals
      compared with control animals.

PMID- 10931383
TI  - Evolution of granulomas in lungs of mice infected aerogenically with
      Mycobacterium tuberculosis.
AB  - Aerogenous infection of C57Bl/6 mice with a virulent strain of Mycobacterium
      tuberculosis (CL 511) leads to the formation of primary granulomas in the lung
      where neutrophils, macrophages and subsequently, lymphocytes accumulate
      progressively around an initial cluster of infected macrophages. The spread of
      infection through the lung parenchyma gives rise to secondary granulomas
      featuring numerous lymphocytes that surround a small number of infected
      macrophages. Afterwards, foamy macrophages add an outer layer to the granulomas,
      which characteristically respect the pulmonary interstitium and remain confined
      within the alveolar spaces. This feature, in conjunction with the constant
      presence of M. tuberculosis in the products of broncho-alveolar lavage, suggests
      that the upward bronchial migration of infected macrophages may contribute
      significantly to pulmonary dissemination of mycobacterial infection. The latter
      would be in agreement with the persistence of chronic pulmonary infection in
      spite of a concomitant strong T helper 1 cell response.

PMID- 10931384
TI  - Dendritic cells enriched from swine thymus co-express CD1, CD2 and major
      histocompatibility complex class II and actively stimulate alloreactive T
      lymphocytes.
AB  - Initial characterization and partial purification of thymic dendritic cells (DC)
      from miniature swine were carried out with the ultimate goal of using these cells
      to induce transplantation tolerance in this preclinical animal model.
      Immunohistochemical analysis of swine thymic tissue sections has shown DC to be
      large cells located in the medullary and the cortico-medullary regions as
      evidenced by the presence of surrounding Hassal bodies. These cells exhibit
      membrane processes and express the CD1, granulocyte/macrophage (G/M), and major
      histocompatibility complex (MHC) class II surface antigens, as well as the S100
      cytosolic and nuclear markers found in humans to be specific for DC. Dendritic
      cells were purified from thymi following collagenase treatment, Percoll gradient
      centrifugation, and adhesion steps to plastic. Cells similar in morphology and
      phenotype to those described in tissue sections were detected in the lighter
      density layers of the gradient and represented 0.02% of the starting cell number.
      Removal of plastic nonadherent cells showed enrichment levels similar to those
      reported for murine and human DC. Two-colour flow cytometric analysis of purified
      pig DC identified these cells as MHC class IIhi, CD1+, CD2+, and G/M+. The
      dendritic nature of these cells was confirmed by their potent ability to
      stimulate alloreactive T lymphocytes. Modification of porcine thymic DC by
      transfer of allogeneic MHC genes and reinjection into the DC donor should permit
      testing of the role of this DC subset in the induction of transplantation
      tolerance.

PMID- 10931386
TI  - Expression of Fc(gamma)r1 (CD64) on polymorphonuclear leucocytes during
      progression to acquired immunodeficiency syndrome in perinatally human
      immunodeficiency virus-infected children.
AB  - CD64, the high-affinity receptor in the family of FCgamma receptors, is not
      expressed constitutively in polymorphonuclear leucocytes (PMN). CD64 is expressed
      by PMNs in the late stages of human immunodeficiency virus (HIV) infection in
      adults. We followed the expression of CD64 on PMNs in perinatally HIV-infected
      children during disease progression. Peripheral blood leucocytes (PBL) from 45
      perinatally HIV-infected paediatric patients and 13 healthy age-matched controls
      were analysed using cytofluorimetry after reaction with a fluorophore-labelled
      monoclonal antibody (MoAb) to CD64. In parallel, we examined the expression of
      CD32, CD16, CD11b and the human neutrophil-specific BH2-Ag using fluorophore
      labelled MoAbs. We found that up to 79.5% of the PMNs in children in class C3
      express CD64. Most importantly, we observed a continuous and significant increase
      in the appearance of CD64+ PMNs as a function of CDC classification (P < 0.001)
      but no changes in the expression of CD32, CD16, CD11b and BH2-Ag. This suggests
      that following the expression of CD64 on PMNs can be useful in evaluating the
      progression of HIV infection in perinatally HIV-infected children.

PMID- 10931385
TI  - Dissection of the role of CD3gamma chains in profound but reversible T-cell
      receptor down-regulation.
AB  - T-lymphocyte activity in the immune system is regulated by the quantity of
      surface membrane T-cell antigen receptors (TCR). The amount of surface-bound TCR
      is dependent on the rate of [1] biosynthesis, assembly and intracellular
      transport of the individual chains composing the TCR/CD3 complex and [2] the
      internalization and recycling of the receptors. The TCR-ligand interaction
      augments receptor internalization. In the present paper, we have studied short-
      and long-term down-regulation of TCR/CD3 complexes with monoclonal anti-TCR/CD3
      antibodies, and attempted to determine which component(s) of the TCR/CD3 complex
      are responsible for these two phenomena. Our data indicate that short- and long
      term down-regulation is mediated by different mechanisms, and that the
      extracellular and/or transmembrane regions of CD3gamma molecules appear to play
      an important role in chronic TCR/CD3 down-regulation and subsequent deficient re
      expression. These results may have important implications for the understanding
      of induction of T-cell tolerance or anergy.

PMID- 10931387
TI  - Polyreactivity of disease-associated anti-RBC IgG autoantibodies of patients with
      warm autoimmune haemolytic anaemia and natural anti-RBC IgG autoantibodies of
      healthy individuals.
AB  - Anti-red blood cell (RBC) immunoglobulin G (IgG) autoantibodies are present in
      patients with warm autoimmune haemolytic anaemia (WAIHA), and, as natural
      autoantibodies, in healthy individuals. This study investigated whether the
      feature of polyreactivity discriminates disease-associated from natural anti-RBC
      IgG autoantibodies. The patterns of reactivity of purified anti-RBC IgG eluted
      from the RBC of WAIHA patients and from the RBC of healthy individuals were
      analysed using quantitative immunoblotting on a panel of whole human tissue or
      bacterial cell extracts as antigen sources. In parallel, the reactivity patterns
      of IgG purified from plasma were analysed. Anti-RBC IgG of WAIHA patients and of
      healthy individuals recognized a wide range of self- and nonself-antigens. The
      reactivity patterns of anti-RBC IgG were homogeneous among patients and controls,
      did not differ between patients and controls, and were similar to those of IgG
      purified from plasma in the case of both patients and healthy individuals. The
      data demonstrate that the anti-RBC IgG autoantibodies of WAIHA patients share
      extensive similarity with those of healthy individuals. Polyreactivity is a
      common feature of both disease-associated and natural anti-RBC IgG
      autoantibodies.

PMID- 10931388
TI  - Changes in cytokine production in vitro during the early phase of birch-pollen
      immunotherapy.
AB  - The kinetics of the immunological mechanisms during allergen-specific
      immunotherapy (IT) has not been thoroughly evaluated. In this investigation we
      study the changes in T-cell responses during the early phase of IT. Ten patients
      (IT group) with birch-pollen allergy were treated with conventional IT. Blood
      samples were collected at regular intervals for specific immunoglobulin (Ig)E
      measurements and preparation of peripheral blood mononuclear cells (PBMC). Seven
      allergic control patients (AC group) were included during the subsequent birch
      pollen season. The PBMC were stimulated with birch-pollen extract or tetanus
      toxoid (TT) and mitogens. After a short decrease, probably owing to seasonal
      variation, the birch-pollen-specific proliferation and the interleukin (IL)-4, IL
      5, and IL-10 production significantly increased when reaching the maintenance
      dose and during the subsequent pollen season. The increase in IL-4 correlated
      with a temporary increased serum level of birch-pollen-specific IgE.
      Interestingly, also the TT-specific response was affected by IT, resulting in
      weaker, but in time similar, changes in proliferation and cytokine production as
      in the birch-pollen-specific response. We speculate that the early phase of IT
      might lead to systemic changes in the capacity of Th2-like cytokine production,
      and that the early increase in allergen-specific IgE is a consequence of enhanced
      IL-4 production.

PMID- 10931389
TI  - HLA-A, B, Cw and DRB1, DRB3/4/5, DQB1, DPB1 frequencies in German immunoglobulin
      A-deficient individuals.
AB  - HLA class I and II frequencies and haplotype frequencies were determined in 80
      German immunoglobulin (Ig)A-deficient individuals and 157 healthy controls with
      normal IgA levels using serological and DNA typing methods. For several alleles,
      significant associations were found, which could be explained mainly in the
      context of a positive association with three different extended haplotypes (HLA
      B*08:DRB1*0301: DQB1*0201, HLA-B*14:DRB1*0102:DQB1*0501 and HLA
      B*44:DRB1*0701:DQB1*0202) and a negative association with a fourth haplotype (HLA
      B*07:DRB1*1501:DQB1*0602). Furthermore, for the first time this study reports a
      positive association of IgA deficiency with DPB1 alleles. Homozygosity rate for
      the gene loci DRB1 and DQB1 was increased in IgA deficiency. Further analysis
      suggested a different pattern of HLA associations depending on the degree of IgA
      deficiency and the gender of the IgA-deficient individuals.

PMID- 10931391
TI  - The ABCs of health education and teaching guides.

PMID- 10931390
TI  - Effects of G-CSF on telomere lengths in PBMCs from human immunodeficiency virus
      infected patients: results from a randomized, placebo-controlled trial.
AB  - Telomeres are unique terminal chromosomal structures, the length of which has
      been shown to decrease with cell division in vitro and with increased age in vivo
      for human somatic cells. In human immunodeficiency virus (HIV)-1 infection,
      decrease of telomere length is primarily found in CD8+ T cells, and not in CD4+ T
      cells. In this double-blind placebo-controlled study, we investigated the effect
      of granulocyte colony stimulating factor (G-CSF) treatment combined with highly
      active antiretroviral therapy (HAART) on mean telomere length in peripheral blood
      mononuclear cells (PBMC). The terminal restriction fragment (TRF) length showed
      no changes during G-CSF treatment although the number of lymphocytes increased
      significantly. The mean TRF length correlated positively (R = 0.552, P = 0.009)
      and negatively (R = -0.503, P = 0.02) to the proportion of CD4+ memory and naive
      cells, respectively. Our data suggest that during G-CSF treatment lymphocytes are
      recruited by a combination of central and peripheral proliferation.

PMID- 10931392
TI  - HIV infection and AIDS in the pediatric population. Implications for home care
      providers.

PMID- 10931393
TI  - The essentials of pain management for cancer patients receiving home care.

PMID- 10931394
TI  - The moral geography of care work.

PMID- 10931395
TI  - Using visual tools with elders who have diabetes.

PMID- 10931396
TI  - Building commitment in today's workforce.

PMID- 10931397
TI  - Reducing falls and resulting hip fractures among older women.

PMID- 10931398
TI  - Psychiatric patients and families: moving from a catastrophic event to long-term
      coping.
AB  - The families of psychiatric patients struggle throughout their member's illness
      with the change it brings and their own feelings about the illness. In the past,
      families were blamed for many of the problems that mentally ill people
      experienced, and although this perception of fault has changed, families still
      experience a catastrophic event when mental illness occurs. Coping will vary
      among families, and all experience grief as a result of their losses. Psychiatric
      home care can help families learn new and adaptive coping skills. Careful family
      assessment can be an important part of the patient's treatment, forming a
      partnership to reintegrate the ill person into the family and home.

PMID- 10931399
TI  - Clinical implications of prospective payment in home health care.
AB  - Now that the final regulations governing the prospective payment system (PPS) for
      home health care have been published in the Federal Register (vol. 65, no. 128,
      July 3, 2000, rules and regulations, p. 41,228), home health agencies (HHAs) can
      begin to finalize their plans to operate efficiently under PPS. Although an
      undercurrent of optimism already is appreciated in response to the PPS, agency
      survival will hinge on fully understanding prospective pay and the data on which
      it is based.

PMID- 10931400
TI  - Vitamin D-deficient rickets: the reemergence of a once-conquered disease.

PMID- 10931401
TI  - The 22q11.2 deletion syndrome: more answers but more questions.

PMID- 10931402
TI  - Lung biopsy in immunocompromised children: when, how, and who?

PMID- 10931403
TI  - Kawasaki disease: who is at risk?

PMID- 10931404
TI  - Nutritional rickets in African American breast-fed infants.
AB  - OBJECTIVE: To analyze the characteristics of infants and children diagnosed with
      nutritional rickets at two medical centers in North Carolina in the 1990s. STUDY
      DESIGN: The physical and radiographic findings, calcium, phosphorus, alkaline
      phosphatase, and 25-hydroxyvitamin D levels of infants and children diagnosed
      with nutritional rickets at two medical centers were reviewed. Breast-feeding
      data were obtained from the North Carolina Women, Infants and Children Program
      (WIC). RESULTS: Thirty patients with nutritional rickets were first seen between
      1990 and June of 1999. Over half of the cases occurred in 1998 and the first half
      of 1999. All patients were African American children who were breast fed without
      receiving supplemental vitamin D. The average duration of breast-feeding was 12.5
      months. The age at diagnosis was 5 to 25 months, with a median age of 15.5
      months. Growth failure was common: length was <5th percentile in 65% of cases,
      and weight was <5th percentile in 43%. CONCLUSION: Factors that may have
      contributed to the increase in referrals of children with nutritional rickets
      include more African American women breast-feeding, fewer infants receiving
      vitamin D supplements, and mothers and children exposed to less sunlight. We
      recommend that all dark-skinned breast-fed infants and children receive vitamin D
      supplementation.

PMID- 10931405
TI  - Dysphagia in children with a 22q11.2 deletion: unusual pattern found on modified
      barium swallow.
AB  - OBJECTIVES: To delineate feeding dysfunction in a population of children with a
      22q11.2 deletion and report the associated findings noted during the modified
      barium swallow (MBS). STUDY DESIGN: Seventy-five children with a chromosome
      22q11.2 deletion and history of persistent feeding difficulty received a feeding
      evaluation, including an MBS for those children for whom there was concern about
      airway penetration. RESULTS: A consistent pattern of feeding difficulty,
      independent of palatal or cardiac involvement, emerged from the evaluations. This
      group typically has trouble coordinating the suck/swallow/breath pattern,
      resulting in slow nipple feedings interrupted by gagging or regurgitation.
      Recurrent vomiting and constipation are common. With advancement to chewable
      table foods, gagging or refusal develops, related to an immature oral transport
      pattern. The MBS studies demonstrate pharyngeal hypercontractility,
      cricopharyngeal prominence, and/or diverticula. CONCLUSIONS: Because of the
      consistency of dysphagic symptoms and MBS findings, we propose that dysmotility,
      especially through the pharyngoesophageal segment, is central to the dysphagia
      affecting this group. Dysphagia related to dysmotility may be underdiagnosed in
      this population or erroneously attributed to cardiac disease. Therefore attention
      to feeding status and investigation with MBS and gastrointestinal studies as
      warranted are recommended for all patients with a 22q11.2 deletion and feeding
      problems.

PMID- 10931406
TI  - Value of open lung biopsy in immunocompromised children.
AB  - OBJECTIVES: To determine the value of open lung biopsy (OLB) in terms of
      diagnosis, morbidity, mortality, and benefits in immunocompromised children with
      pulmonary involvement. STUDY DESIGN: We retrospectively reviewed 36 OLBs
      performed in 32 immunocompromised children between 1985 and 1998. Seventeen
      biopsies were performed in patients with primary immunodeficiency syndromes and
      19 in patients with secondary immunodeficiency syndromes. Twenty-eight biopsies
      were performed because of a lack of response to ongoing antimicrobial treatments
      with negative or positive findings on bronchoalveolar lavage (BAL) and a
      deteriorating clinical or radiologic course, and 8 biopsies were performed
      because of persistent chest x-ray infiltrates. RESULTS: Diffuse pulmonary
      infiltrates were observed on chest x-ray in 28 cases, hyperinflation in 3 cases,
      and nodular infiltrates in 5 cases. A histopathologic diagnosis was possible for
      all 36 OLBs. Specific diagnosis was obtained in 22 (61%) (12 infectious agents, 6
      tumors, 4 bronchiolitis obliterans) and non-specific diagnosis in 14 (39%). Fungi
      were the main infectious agents (8 of 12). For the diagnosed infections, BAL
      provided 4 true-positive, 3 false-positive, and 6 false-negative results.
      Specific treatment was changed in 77% of cases, providing real benefits in 12
      (33%) cases. The morbidity and overall mortality rates were 31% and 33%,
      respectively. The mortality rate was significantly higher in the first 30 days
      after OLB in patients receiving ventilatory assistance (58%). CONCLUSIONS: OLB in
      immunocompromised children with deteriorating clinical or radiologic course is a
      sensitive diagnostic tool.

PMID- 10931407
TI  - Prediction of non-responsiveness to intravenous high-dose gamma-globulin therapy
      in patients with Kawasaki disease at onset.
AB  - Children with Kawasaki disease (n = 82), treated with intravenous immune globulin
      (IVIG) at a high dose, were classified as IVIG-responsive (defervescence within 5
      days of starting IVIG, n = 69) or IVIG-non-responsive (consistent fever over a 6
      day period since starting IVIG, n = 13). One patient in the IVIG-responsive group
      had a coronary artery abnormality during the acute phase (1. 4%) versus 5 in the
      IVIG-non-responsive group (38.5%). Age, duration of fever before the initiation
      of IVIG therapy, and laboratory data obtained on admission were tested by the
      Mann-Whitney U test. Serum levels of C-reactive protein, total bilirubin, lactate
      dehydrogenase, and gamma-glutamyltranspeptidase were significantly higher (P
      =.002, P <.001, P <.034, and P <.038, respectively), and the hemoglobin value was
      significantly lower (P =.025) in patients in the non-responsive group. A
      multivariate analysis showed that serum levels of C-reactive protein (P =.006),
      lactate dehydrogenase (P =. 035), and total bilirubin (P =.046) on admission were
      independent correlates of the success of IVIG therapy. By defining the predictive
      values, patients with a C-reactive protein level >10 mg/dL, LDH level >590 IU/L,
      and/or hemoglobin value <10 g/dL are considered non-responsive to IVIG.
      Additional therapy at an early stage of the disease should be considered for
      patients who are predicted to be IVIG-non-responsive.

PMID- 10931408
TI  - Predictors of coronary artery lesions after intravenous gamma-globulin treatment
      in Kawasaki disease.
AB  - OBJECTIVE: We evaluated the efficacy of intravenous gamma-globulin (IVGG)
      administration for children with Kawasaki disease to establish whether
      additional, more advanced therapy is needed in intractable cases. STUDY DESIGN: A
      total of 193 children with Kawasaki disease were studied retrospectively.
      Patients were admitted 3 to 7 days after the onset of the disease, and IVGG was
      administered. Laboratory measurements including white blood cell (WBC),
      neutrophil, and platelet counts and C-reactive protein (CRP) and albumin
      concentrations were determined before and 2 to 3 days after IVGG treatment. The
      progression of coronary artery lesions (CALs) was monitored by serial
      echocardiography until 30 days after treatment. RESULTS: Of 193 children, 24
      (12.2 %) had CALs including transient dilatation. In contrast to the other
      measurements, the WBC count increased in 21 of 24 (87.5%) children with CALs
      after IVGG therapy. The patients with increased neutrophil count and CRP
      concentration after IVGG therapy also had CAL formation at a high rate (78.3% and
      66.7%, respectively). Among children with normal coronary arteries, elevations of
      the WBC and neutrophil counts and CRP concentration were observed after IVGG
      therapy in only 3, 6, and 8 patients, respectively (specificity: 98.2%, 97.0%,
      and 95.3%, respectively). Furthermore, multiple logistic regression indicated
      that these variables were useful predictors of CALs in KD. CONCLUSION: Though the
      introduction of IVGG therapy has improved the prognosis of Kawasaki disease,
      approximately 10% of patients still develop CALs. The need for more aggressive
      therapy in IVGG-resistant cases can be recognized early by increases in the WBC
      and neutrophil counts and serum CRP concentration after IVGG administration.

PMID- 10931409
TI  - Catheter interventional treatment in Kawasaki disease: A report from the Japanese
      Pediatric Interventional Cardiology Investigation group.
AB  - OBJECTIVE: To assess the current status of catheter intervention in Kawasaki
      disease and to evaluate its efficacy and outcome. STUDY DESIGN: A questionnaire
      was sent to 55 major institutions in Japan. RESULTS: A total of 58 procedures in
      57 patients were reported. The median age at the time of intervention was 12.1
      years. The procedures included percutaneous transluminal coronary angioplasty
      (PTCA; n = 34), percutaneous transluminal coronary rotational ablation (PTCRA; n
      = 13), directional coronary atherectomy (DCA; n = 4), and stent implantation (n =
      7). The immediate success rate was 74% for PTCA, 100% for PTCRA, 100% for DCA,
      and 86% for stents. The interval from the onset of disease to intervention in
      successful PTCA (n = 25) was significantly shorter than that in unsuccessful PTCA
      (n = 9). Restenosis after PTCA was observed in 24%. Development of new coronary
      aneurysms was reported in 3 patients for PTCA, 2 for PTCRA, 3 for DCA, and 1 for
      stents. Except for the DCA, all new aneurysms were associated with the use of
      high-pressure balloon inflation. Two deaths were reported as acute complications.
      CONCLUSIONS: Catheter intervention is a promising therapeutic strategy in the
      management of coronary stenosis caused by Kawasaki disease. Care should be paid
      to avoid acute coronary arterial complications and the development of new
      coronary aneurysms.

PMID- 10931410
TI  - Neutropenia, neutrophil dysfunction, and inflammatory bowel disease in glycogen
      storage disease type Ib: results of the European Study on Glycogen Storage
      Disease type I.
AB  - OBJECTIVE: To investigate the incidence, the severity, and the course of
      neutropenia, neutrophil dysfunction, and inflammatory bowel disease (IBD) in
      glycogen storage disease (GSD) type Ib. METHOD: As part of a collaborative
      European Study on GSD type I, a retrospective registry was established in 12
      European countries that included all patients with GSD-I who were known at the
      centers and were born from 1960 to 1995. Of a total of 288 patients with GSD-I,
      57 who had GSD-Ib form the basis of this study. RESULTS: Neutropenia (defined as
      an absolute neutrophil count <1 x 10(9)/L) was found in 54 patients. In 64% of
      the patients neutropenia was documented before the age of 1 year, but in 18% of
      the patients neutropenia was first noted between the ages of 6 and 9 years.
      Neutropenia was persistent in 5 patients and intermittent without any clear
      cyclical course in 45. Neutrophil function was investigated in 18 patients with
      neutropenia and was abnormal in all. Perioral infections were reported in 37
      patients, perianal infections in 27 patients, and protracted diarrhea in 23
      patients. Findings on colonoscopy and radiologic studies in 10 of 20 patients
      suspected to have IBD were abnormal in all. All patients with IBD, perioral
      infections, and perianal infections had neutropenia. CONCLUSIONS: Intermittent
      severe neutropenia is frequently found in patients with GSD-Ib. The study also
      indicates that IBD in GSD-Ib is underdiagnosed; up to 77% of the patients studied
      had evidence of IBD, all of whom had neutropenia. IBD was not detected in those
      with normal neutrophil counts. These findings support the notion that neutropenia
      and/or neutrophil dysfunction in GSD-Ib and IBD are causally related.

PMID- 10931411
TI  - Use of infliximab in the treatment of Crohn's disease in children and
      adolescents.
AB  - BACKGROUND: Crohn's disease is often poorly responsive to conventional therapy
      with corticosteroids and immunomodulators. A novel chimeric antibody to tumor
      necrosis factor-alpha, infliximab, has shown utility in the treatment of
      refractory Crohn's disease in adults. PURPOSE: To evaluate the efficacy of open
      label administration of infliximab in children and adolescents with active
      intestinal Crohn's disease. METHODS: Chart review of the experience with 19
      subjects (mean age 14.4 years, range 9 to 19 years) receiving 1 to 3 infusions of
      infliximab (5 mg/kg/dose) over a 12-week period for corticosteroid-resistant
      disease (n = 7) or corticosteroid dependence (n = 12). Disease activity was
      monitored by physician global assessment and the Pediatric Crohn's Disease
      Activity Index. RESULTS: Significant initial improvement (first 4 weeks after
      infusion) was noted in all subjects, with Pediatric Crohn's Disease Activity
      Index values decreasing significantly (mean +/- SD, 42.1 +/- 13.7 to 10.0 +/-
      5.6, P <.0001). Over the subsequent 8-week period, 8 of 19 treated subjects had
      worsening of symptoms, although none deteriorated to severe activity. The mean
      Pediatric Crohn's Disease Activity Index at 12 weeks was 26.8 +/- 16. 4. The mean
      daily prednisone dosages at baseline, 4 weeks, and 12 weeks were 28 +/- 14 mg, 20
      +/- 12 mg, and 8 +/- 12 mg, respectively (P <.01). Adverse effects were noted in
      3 patients during infusion (dyspnea, rash) and were self-limited. CONCLUSIONS:
      Infliximab is associated with short-term clinical improvement in children and
      adolescents with severe Crohn's disease. The rapid return of disease activity in
      some patients suggests that additional dosing strategies may be required. Long
      term safety necessitates close monitoring.

PMID- 10931412
TI  - Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed
      cell death in infants and children after severe traumatic brain injury.
AB  - OBJECTIVES: To determine whether bcl-2, a protein that inhibits apoptosis, would
      be increased in cerebrospinal fluid (CSF) in infants and children after traumatic
      brain injury (TBI) and to examine the association of bcl-2 concentration with
      clinical variables. STUDY DESIGN: Bcl-2 was measured in CSF from 23 children
      (aged 2 months-16 years) with severe TBI and from 19 children without TBI or
      meningitis (control subjects) by enzyme-linked immunosorbent assay. CSF
      oligonucleosome concentration was also determined as a marker of DNA degradation.
      Brain samples from 2 patients undergoing emergent decompressive craniectomies
      were analyzed for bcl-2 with Western blot and for DNA fragmentation with TUNEL
      (terminal deoxynucleotidyl-transferase mediated biotin-dUTP nick-end labeling).
      RESULTS: CSF bcl-2 concentrations were increased in patients with TBI versus
      control subjects (P =.01). Bcl-2 was increased in patients with TBI who survived
      versus those who died (P =.02). CSF oligonucleosome concentration tended to be
      increased after TBI (P =.07) and was not associated with bcl-2. Brain tissue
      samples showed an increase in bcl-2 in patients with TBI versus adult brain bank
      control samples and evidence of DNA fragmentation within cells with apoptotic
      morphology. CONCLUSIONS: Bcl-2 may participate in the regulation of cell death
      after TBI in infants and children. The increase in bcl-2 seen in patients who
      survived is consistent with a protective role for this anti-apoptotic protein
      after TBI.

PMID- 10931413
TI  - Stature, weight, and body mass among young US children born at term with
      appropriate birth weights.
AB  - OBJECTIVE: To describe weight, stature, and body mass index (BMI) changes
      occurring before the age of 7 years, which may influence the prevalence of
      overweight in adolescence and adulthood. METHODS: Regression models predicting
      height and weight at ages 2 months to 6. 75 years were based on the third
      National Health and Nutrition Examination Survey. Birth certificate data were
      used to adjust ethnic-specific models for birth weight for gestational age.
      RESULTS: Attained height is higher for non-Hispanic black children than for
      either non-Hispanic white or Mexican American children (P </=.001). Weights at 2
      months, 2 years, and 6.75 years are similar among racial/ethnic groups after
      adjustments. Mexican American children at ages 2 to 6.75 years had higher
      prevalences of BMI >85th percentile than either non-Hispanic white or black
      children (boys = 25.6%, SE = 2.7 compared with 14.1%, SE = 1.7 and 16.5%, SE =
      1.7, respectively; girls = 21.9%, SE = 3.6 compared with 13.0%, SE = 1.7 and
      13.7%, SE = 2.2, respectively). For non-Hispanic whites and Mexican Americans and
      for non-Hispanic black boys, BMI decreased slightly between ages 2 and 6.75
      years; BMI for non-Hispanic black girls did not. CONCLUSION: Size differences
      before the age of 7 years may influence later ethnic-specific overweight
      prevalence, independent of prenatal influences.

PMID- 10931414
TI  - Pancreatic function and extended mutation analysis in DeltaF508 heterozygous
      infants with an elevated immunoreactive trypsinogen but normal sweat electrolyte
      levels.
AB  - BACKGROUND: Newborn screening for cystic fibrosis (CF) with immunoreactive
      trypsinogen (IRT) and DeltaF508 analysis followed by sweat testing misses some
      infants with CF and detects more DeltaF508 carriers than expected. Some of the
      apparent DeltaF508 carriers may be DeltaF508 compound heterozygotes with normal
      sweat electrolyte levels. METHODS: Infants identified by newborn screening with
      an elevated IRT level, one DeltaF508 allele, and a sweat chloride level <60
      mmol/L underwent CF mutation analysis, pancreatic stimulation testing, and repeat
      IRT analysis followed by clinical review and repeat sweat test at 12 months.
      RESULTS: Over a 24-month period we identified 122 DeltaF508 heterozygotes and
      recruited 57; 4 had borderline sweat chloride levels (40 to 60 mmol/L), 5 (8.8%,
      95% CI 1.4, 16.2) had a second CF mutation (R117H), and 11 (20%, 95% CI 10, 30)
      had the intron 8 5T allele. Three had clinical CF at 12 months (initial sweat
      chloride levels: 53, 51, and 32 mmol/L). Pancreatic electrolyte secretion in the
      subjects with a borderline sweat chloride level was similar to that in patients
      with known CF. CONCLUSION: The excess of DeltaF508 heterozygotes detected by
      IRT/DNA screening is associated with the presence of a second mutation or the 5T
      allele in some infants. Screened infants with borderline sweat chloride levels
      almost certainly have CF, but long-term follow-up of the infants with the
      genotype DeltaF508/R117H and DeltaF508/5T is required to determine their outcome.
      In the meantime, newborn screening should be confined to severe mutations
      associated with classic CF.

PMID- 10931415
TI  - Urine culture from bag specimens in young children: are the risks too high?
AB  - OBJECTIVE: To compare the risks of contaminated culture results and consequent
      adverse clinical outcomes in urine specimens obtained by "clean-voided" bag
      method versus catheterization. STUDY DESIGN: Hospital-based cohort study of all
      children </=24 months with outpatient urine cultures (n = 7584) obtained from
      January 1993 to December 1995. Medical records were followed up for all children
      with contaminated culture results who had 1 or more additional cultures within 7
      days of the original culture. Contamination rates of bag urine cultures from the
      emergency department and a pediatric test center were compared. RESULTS:
      Contamination rates were 62.8% and 9.1% (P <.001) in bag versus catheter
      specimens, respectively. Contamination rates of bag urine specimens collected in
      the emergency department and pediatric test center were 56.4% versus 69. 25%,
      respectively. Of the 3440 contaminated urines, 132 (1.7%) resulted in 1 or more
      adverse clinical outcomes. Adjusted odds ratios (and 95% CI) for these outcomes
      in bag versus catheter specimens were as follows: 4.9 (2.3 to 10.5) for
      unnecessary recall, infinite for delayed diagnosis and treatment, 4.8 (1.8 to
      12.4) for unnecessary treatment, 15.6 (2.1 to 116.8) for unnecessary prolonged
      treatment, 4.1 (1.4 to 12.1) for unnecessary radiologic investigation, and 12.4
      (1.6 to 95.5) for unnecessary hospital admission. CONCLUSIONS: The risks of the
      "noninvasive" bag urine culture appear to exceed its benefits.

PMID- 10931416
TI  - Respiratory syncytial virus pneumonia in the hospital setting: length of stay,
      charges, and mortality.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the most important viral cause
      of lower respiratory tract infection in infants and young children worldwide. No
      vaccine against RSV is available, but prophylactic interventions have been shown
      to be safe and effective in clinical trials. OBJECTIVES: This retrospective
      analysis was conducted to examine the health and economic burden of
      hospitalization for RSV pneumonia. METHODS: Nationally weighted hospital
      discharges for RSV pneumonia among children 4 years old and younger were analyzed
      by using the Healthcare Cost and Utilization Project National Inpatient Sample.
      RESULTS: In 1993, there were estimated to be 16,500 hospital discharges with RSV
      pneumonia, which increased to 19,700 and 20,800 in 1994 and 1995, respectively.
      Children less than 1 year of age accounted for over 70% of these discharges.
      Hospital charges (in 1998 dollars) for RSV pneumonia-associated episodes were
      $295,100,000 in 1993; $392,300,000 in 1994; and $295,800,000 in 1995.
      CONCLUSIONS: With inpatient charges of $300 to $400 million per year in the
      United States, the disease burden of RSV pneumonia is very high in terms of both
      morbidity and economic costs. Emerging prophylactic interventions should have an
      impact on the high burden of RSV pneumonia.

PMID- 10931417
TI  - Alterations in sleep physiology in young children with insulin-dependent diabetes
      mellitus: relationship to nocturnal hypoglycemia.
AB  - OBJECTIVES: To examine the effect of diabetes per se and nocturnal hypoglycemia
      on sleep in children with insulin-dependent diabetes mellitus (IDDM). DESIGN:
      Overnight polysomnography was performed on 3 occasions in 29 children with IDDM -
      twice during metabolic profiling. Sleep data were analyzed from 14 children
      (median [range], 8.7 [5.9 to 12.9] years) with a night of hypoglycemia and a
      nonhypoglycemic night. Seven children in the control group (9 [5.6 to 11.4]
      years) underwent 2 nights of polysomnography, once during metabolic profiling (to
      assess the effects of metabolic profiling), and 15 members of the control group
      had polysomnography only (to assess the effects of diabetes per se and to compare
      with the index group). RESULTS: Children with IDDM had disrupted sleep compared
      with the control group (short wakes, percentage of sleep time, 0.8 [0.5 to 1.9]
      vs 0.0 [0.0 to 0.3], median [interquartile range], IDDM vs control group,
      respectively, P =.001; long wakes, 1.2 [0.7 to 3. 0] vs 0.0 [0.0 to 0.0], P
      =.033; total number of wakes, 6 [3.5 to 11. 5] vs 1 [0 to 2], P =.002). Blood
      sampling disrupted sleep with increased long wakes as percentage of sleep time
      (0.3 [0.0 to 3.8] vs 4.3 [3.1 to 16.9], nonsampling vs sampling night,
      respectively, P =.003). Episodes of hypoglycemia were profound, with a glucose
      nadir of 2.0 [1.4 to 3.3] mmol/L (35.0 [24.5 to 57.8] mg/dL) and prolonged, 308
      [30 to 630] minutes, with no effect on sleep. CONCLUSIONS: Children with diabetes
      had disrupted sleep compared with a control group, but there was no effect of
      profound nocturnal hypoglycemia on sleep quality. J Pediatr 2000;137:233-8)

PMID- 10931419
TI  - Increased need for medical interventions in infants with velocardiofacial
      (deletion 22q11) syndrome.
AB  - Ten of 12 patients diagnosed with deletion 22q11.2 in infancy required a total of
      26 hospitalizations during their first year of life. After heart disease, feeding
      and respiratory problems were the most frequent reasons for intervention.

PMID- 10931418
TI  - Calcium-stimulated insulin secretion in diffuse and focal forms of congenital
      hyperinsulinism.
AB  - OBJECTIVES: To identify infants with hyperinsulinism caused by defects of the
      beta-cell adenosine triphosphate-dependent potassium channel complex and to
      distinguish focal and diffuse forms of hyperinsulinism caused by these mutations.
      STUDY DESIGN: The acute insulin response to intravenous calcium stimulation
      (CaAIR) was determined in 9 patients <20 years with diffuse hyperinsulinism
      caused by defective beta-cell sulfonylurea receptor (SUR1(-/-)), 3 patients with
      focal congenital hyperinsulinism (6 weeks to 18 months), a 10-year-old with
      insulinoma, 5 with hyperinsulinism/hyperammonemia syndrome caused by defective
      glutamate dehydrogenase (6 months to 28 years), 4 SUR1(+/-) heterozygotes with no
      symptoms, and 9 normal adults. Three infants with congenital focal disease, 1
      with diffuse hyperinsulinism, and the child with insulinoma underwent selective
      pancreatic intra-arterial calcium stimulation with hepatic venous sampling.
      RESULTS: Children with diffuse SUR1(-/-) disease and infants with congenital
      focal hyperinsulinism responded to CaAIR, whereas the normal control group,
      patients with hyperinsulinism/hyperammonemia syndrome, and SUR1(+/-) carriers did
      not. Selective arterial calcium stimulation of the pancreas with hepatic venous
      sampling revealed selective, significant step-ups in insulin secretion that
      correlated anatomically with the location of solitary lesions confirmed
      surgically in 2 of 3 infants with congenital focal disease and in the child with
      insulinoma. Selective arterial calcium stimulation of the pancreas with hepatic
      venous sampling demonstrated markedly elevated baseline insulin levels throughout
      the pancreas of the infant with diffuse hyperinsulinism. CONCLUSIONS: The
      intravenous CaAIR is a safe and simple test for identifying infants with diffuse
      SUR1(-/-) hyperinsulinism or with focal congenital hyperinsulinism. Preoperative
      selective arterial calcium stimulation of the pancreas with hepatic venous
      sampling can localize focal lesions causing hyperinsulinism in children. The
      combination of these calcium stimulation tests may help distinguish focal lesions
      suitable for cure by local surgical resection.

PMID- 10931420
TI  - Kawasaki disease in older children and adolescents.
AB  - Features of 28 patients older than 8 years of age with acute Kawasaki disease
      were reviewed. Observations included a predominance of male patients and white
      patients, delays in diagnosis of acute Kawasaki disease, presence of additional
      signs and symptoms, and a substantial incidence of coronary artery abnormalities
      (21%) including mild transient changes.

PMID- 10931421
TI  - Glycogen storage disease type Ib without neutropenia.
AB  - We report 2 patients with atypical glycogen storage disease type Ib without
      neutropenia or infectious complications. Neither patient was deficient in hepatic
      glucose-6-phosphatase activities in microsome-disrupted homogenates; both had
      mutations in the glucose-6-phosphate transporter gene, suggesting an allelic
      variant of glycogen storage disease type Ib.

PMID- 10931422
TI  - Short-chain hydroxyacyl-coenzyme A dehydrogenase deficiency presenting as
      unexpected infant death: A family study.
AB  - We describe a case of liver-specific short-chain hydroxyacyl-coenzyme A
      dehydrogenase deficiency. Enzymatic confirmation of heterozygosity was shown in
      family members, illustrating the recessive nature of this new disorder.
      Heterozygous carriers did not present with biochemical abnormalities when
      challenged by fasting.

PMID- 10931423
TI  - Congenital nasal pyriform aperture stenosis associated with central diabetes
      insipidus.
AB  - We describe a child who has central diabetes insipidus associated with congenital
      nasal pyriform aperture stenosis without any apparent anterior pituitary
      dysfunction. This association further strengthens the concept that congenital
      nasal pyriform aperture stenosis may be a microform of holoprosencephaly.

PMID- 10931424
TI  - Gluten-dependent diabetes-related and thyroid-related autoantibodies in patients
      with celiac disease.
AB  - Patients with celiac disease are at high risk of having autoimmune disorders.
      Moreover, untreated patients with celiac disease have been found to have a higher
      than expected prevalence of organ-specific autoantibodies. In a prospective study
      of 90 patients with celiac disease, we found that the prevalence of diabetes and
      thyroid-related serum antibodies was 11.1% and 14.4%, respectively. Like
      antiendomysium autoantibodies, these organ-specific antibodies seem to be gluten
      dependent and tend to disappear during a gluten-free diet.

PMID- 10931425
TI  - Unusual complications of warfarin therapy: skin necrosis and priapism.
AB  - Skin necrosis and priapism are unusual complications of warfarin therapy. We
      report a teenager with warfarin-associated skin necrosis and priapism who was
      subsequently found to be a compound heterozygote for protein C deficiency and a
      heterozygote for the factor V Leiden mutation.

PMID- 10931427
TI  - Deletion of NKX2.1 gene encoding thyroid transcription factor-1 in two siblings
      with hypothyroidism and respiratory failure.
AB  - Thyroid transcription factor-1 encoded by the NKX2.1 gene is a candidate
      regulator of thyroid and lung morphogenesis and function in humans. We report 2
      female siblings with congenital thyroid dysfunction and recurrent acute
      respiratory distress carrying a heterozygous deletion of chromosome 14q12-13.3,
      resulting in haploinsufficiency for the NKX2.1 gene. This observation further
      supports a physiologic role for thyroid transcription factor-1 in early human
      thyroid and pulmonary function.

PMID- 10931426
TI  - The use of naproxen in the treatment of children with rheumatic fever.
AB  - We evaluated the efficacy and safety of naproxen (10-20 mg/kg/d) for the
      treatment of arthritis and fever related to rheumatic fever in 19 children. Fever
      and arthritis resolved within a median of 1 day of beginning treatment (range, 1
      2 and 1-30 days, respectively). The sole patient with prolonged arthritis had
      small joint involvement. No gastrointestinal, dermatologic, liver, or renal side
      effects were observed. None of the patients developed carditis over the following
      6 months. Naproxen appears to be effective for the treatment of arthritis and
      fever related to rheumatic fever and is well tolerated.

PMID- 10931428
TI  - Edible "bird's nest"-induced anaphylaxis: An under-recognized entity?
AB  - The Chinese delicacy "bird's nest" is the most common cause of food-induced
      anaphylaxis requiring hospitalization among Chinese children in Singapore. This
      investigation has established an immunoglobulin E-mediated cause and has
      characterized the major putative allergens.

PMID- 10931430
TI  - Identification of two subtypes of infantile acid maltase deficiency.
AB  - Infantile patients with acid maltase deficiency have severe hypertrophic
      cardiomyopathy, left ventricular outflow obstruction, and generalized muscle
      weakness and die before 1 year of age. We identified 12 infants with acid maltase
      deficiency who had a similar clinical presentation but less severe cardiomyopathy
      and absence of left ventricular outflow obstruction, and 9 of 12 had longer
      survival with assisted ventilation and supplemental intubation.

PMID- 10931429
TI  - KL-6, a mucinous glycoprotein, as an indicator of chronic lung disease of the
      newborn.
AB  - KL-6 is a mucinous glycoprotein that is preferentially expressed by alveolar type
      2 cells. Plasma KL-6 was higher in infants with chronic lung disease (n = 12)
      than in infants without chronic lung disease (n = 14) on day 0-1, 10, and 30 (P
      =.04). KL-6 correlated with the alveolar-arterial oxygen tension difference on
      day 10 and day 30. Plasma KL-6 may be useful as an early marker of chronic lung
      disease and an indicator of severity.

PMID- 10931431
TI  - An "owl's eyes" view of hydroceles.

PMID- 10931433
TI  - Reply

PMID- 10931434
TI  - (In)efficacy of cisapride.

PMID- 10931432
TI  - Effects of cisapride on QT interval in infants: A prospective study.

PMID- 10931435
TI  - Reply

PMID- 10931437
TI  - Editorial announcement

PMID- 10931436
TI  - T-cell-depleted bone marrow transplantation from unrelated donor for [correction
      of allogeneic sibling for] X-linked hyperimmunoglobulin M syndrome.

PMID- 10931438
TI  - Editorial

PMID- 10931439
TI  - Amphipathic, alpha-helical antimicrobial peptides.
AB  - Gene-encoded antimicrobial peptides are an important component of host defense in
      animals ranging from insects to mammals. They do not target specific molecular
      receptors on the microbial surface, but rather assume amphipathic structures that
      allow them to interact directly with microbial membranes, which they can rapidly
      permeabilize. They are thus perceived to be one promising solution to the growing
      problem of microbial resistance to conventional antibiotics. A particularly
      abundant and widespread class of antimicrobial peptides are those with
      amphipathic, alpha-helical domains. Due to their relatively small size and
      synthetic accessibility, these peptides have been extensively studied and have
      generated a substantial amount of structure-activity relationship (SAR) data. In
      this review, alpha-helical antimicrobial peptides are considered from the point
      of view of six interrelated structural and physicochemical parameters that
      modulate their activity and specificity: sequence, size, structuring, charge,
      amphipathicity, and hydrophobicity. It begins by providing an overview of how
      these vary in peptides from different natural sources. It then analyzes how they
      relate to the currently accepted model for the mode of action of alpha-helical
      peptides, and discusses what the numerous SAR studies that have been carried out
      on these compounds and their analogues can tell us. A comparative analysis of the
      many alpha-helical, antimicrobial peptide sequences that are now available then
      provides further information on how these parameters are distributed and
      interrelated. Finally, the systematic variation of parameters in short model
      peptides is used to throw light on their role in antimicrobial potency and
      specificity. The review concludes with some considerations on the potentials and
      limitations for the development of alpha-helical, antimicrobial peptides as
      antiinfective agents.

PMID- 10931440
TI  - Structural features and biological activities of the cathelicidin-derived
      antimicrobial peptides.
AB  - Cathelicidins are a numerous group of mammalian proteins that carry diverse
      antimicrobial peptides at the C-terminus of a highly conserved preproregion.
      These peptides, which become active when released from the proregion, display a
      remarkable variety of sizes, sequences, and structures, and in fact comprise
      representatives of all the structural groups in which the known antimicrobial
      peptides have been classified. Most of the cathelicidin-derived peptides exert a
      broad spectrum and potent antimicrobial activity and also bind to
      lipopolysaccharide and neutralize its effects. In addition, some of them have
      recently been shown to exert other activities and might participate in host
      defense also by virtue of their ability to induce expression of molecules
      involved in a variety of biological processes. This review is aimed at providing
      a general overview of the cathelicidins and of the peptides derived therefrom,
      with emphasis on aspects such as structure, biological activities in vitro and in
      vivo, and structure/activity relationship studies.

PMID- 10931441
TI  - Class II antimicrobial peptides from lactic acid bacteria.
AB  - Strains of lactic acid bacteria (LAB) produce a wide variety of antibacterial
      peptides. More than fifty of these so-called peptide bacteriocins have been
      isolated in the last few years. They contain 20-60 amino acids, and are cationic
      and hydrophobic in nature. Several of these bacteriocins consist of two
      complementary peptides. The peptide bacteriocins of LAB are inhibitory at
      concentrations in the nanomolar range, and cause membrane permeabilization and
      leakage of intracellular components in sensitive cells. The inhibitory spectrum
      is limited to gram-positive bacteria, and in many cases to bacteria closely
      related to the producing strain. Among the target organisms are food spoilage
      bacteria and pathogens such as Listeria, so that many of these antimicrobial
      peptides could have a potential as food preservatives as well as in medical
      applications.

PMID- 10931442
TI  - Posttranslationally modified bacteriocins--the lantibiotics.
AB  - Lantibiotics are a subgroup of bacteriocins that are characterized by the
      presence of the unusual thioether amino acids lanthionine and 3-methyllanthionine
      generated through posttranslational modification. The biosynthesis of
      lantibiotics follows a defined pathway comprising modifications of the
      prepeptide, proteolytic activation, and export. The genes encoding the
      biosynthesis apparatus and the lantibiotic prepeptide are organized in clusters,
      which also include information for proteins involved in regulation and producer
      self-protection. The elongated cationic lantibiotics primarily act through the
      formation of pores and recent progress with nisin and epidermin has shown that
      specific docking molecules such as lipid II play an essential role in this
      mechanism. Mersacidin and actagardine inhibit cell wall biosynthesis by
      complexing the precursor lipid II, whereas the cinnamycin-like peptides bind to
      phosphoethanolamine thus inhibiting phospholipase A2.

PMID- 10931443
TI  - Combinatorial libraries: a tool to design antimicrobial and antifungal peptide
      analogues having lytic specificities for structure-activity relationship studies.
AB  - In the race for supremacy, microbes are sprinting ahead. This warning by the
      World Health Organization clearly demonstrates that the spread of antibiotic
      resistant bacteria leads to a global health problem and that antibiotics never
      seen before by bacteria are urgently needed. Antimicrobial peptides represent
      such a source for novel antibiotics due to their rapid lytic activity (within
      minutes) through disruption of cell membranes. However, due to the similarities
      between bacterial, fungal, and mammalian plasma cell membranes, a large number of
      antimicrobial peptides have low lytic specificities and exhibit a broad activity
      spectrum and/or significant toxic effect toward mammalian cells. Mutation
      strategies have allowed the development of analogues of existing antimicrobial
      peptides having greater lytic specificities, although such methods are lengthy
      and would be more efficient if the molecular mechanisms of action of
      antimicrobial peptides were clearly elucidated. Synthetic combinatorial library
      approaches have brought a new dimension to the design of novel biologically
      active compounds. Thus, a set of peptide analogues were generated based on the
      screening of a library built around an existing lytic peptide, and on a
      deconvolution strategy directed toward activity specificity. These peptide
      analogues also served as model systems to further study the effect of biomembrane
      mimetic systems on the peptides structural behavior relevant to their biological
      activities.

PMID- 10931445
TI  - Integration of cost-effective early detection programs into the health services
      of developing countries.

PMID- 10931444
TI  - Development of protegrins for the treatment and prevention of oral mucositis:
      structure-activity relationships of synthetic protegrin analogues.
AB  - Protegrin antimicrobial peptides possess activity against gram-positive and gram
      negative bacteria and yeasts. An extensive structure-activity relationship (SAR)
      study was conducted on several hundred protegrin analogues to gain understanding
      of the relationship between the primary and secondary structure of the protegrins
      and their antimicrobial activities, and to identify a protegrin analogue for
      clinical development. Native sequence protegrins are cationic, amphiphilic
      peptides that are characterized by the presence of a beta-sheet structure that is
      maintained by two disulfide bridges. The presence of the beta-sheet is key to the
      stability of the protegrin structure; linearized analogues or analogues that have
      amino acid substitutions that eliminate hydrogen bonding across the beta-sheet
      have reduced activity, especially in the presence of physiological concentrations
      of NaCl. Also, maintaining amphiphilicity of the beta-sheet is key; analogues
      with substitutions of polar amino acids in the hydrophobic face have reduced
      activity. Analogues with reduced positive charge tend to be less active, an
      observation that is more marked for gram-negative than gram-positive bacteria,
      and may implicate binding to lipopolysaccharide as a key mechanistic step in the
      killing of gram-negative bacteria. A very large number of amino acid
      substitutions are tolerated by the protegrin structure, implying that overall
      structural features such as amphiphilicity, charge, and shape are more important
      to activity than the presence of specific amino acids. This lack of importance of
      specific stereochemistry is supported by the fact that completely D-amino acid
      substituted protegrins are fully potent. Based on the SAR studies, and on the
      microbiological data from an animal model, one protegrin analogue, IB-367, was
      selected for clinical development as a topical agent to prevent the oral
      mucositis associated with cancer therapy.

PMID- 10931446
TI  - Immunostained cathepsins B and L correlate with depth of invasion and different
      metastatic pathways in early stage gastric carcinoma.
AB  - BACKGROUND: With the recent development of minimal treatment for early stage
      gastric carcinoma, identifying specific indicators of the metastatic potential of
      primary tumors has become more important. Cathepsin B and cathepsin L, both
      lysosomal cysteine proteases, degrade the extracellular matrix during tumor
      progression. Although many studies have shown their relation to human cancer
      progression, little is known about their roles in the early stage. The
      clinicopathologic significance of cathepsins was therefore studied in early stage
      gastric carcinoma. METHODS: Expression of both cathepsins was studied
      immunohistochemically in 51 tissue specimens from gastric carcinomas that invaded
      the submucosal layer or muscularis propria. The relation between their expression
      and clinicopathologic factors was analyzed. RESULTS: Both cathepsins were
      expressed at higher levels in tumors that invaded the muscularis propria than in
      those within the submucosa (P < 0.05). In addition, tumors with lymphatic
      invasion showed higher cathepsin B expression than those without it (P < 0.05),
      whereas tumors with venous invasion showed higher cathepsin L expression than
      those without it (P < 0.05). No other clinicopathologic factors correlated with
      expression of either cathepsin. CONCLUSIONS: Tumors with overexpression of
      cathepsins have powerful potential for invasiveness in the early stage of gastric
      carcinoma. Moreover, the authors hypothesize that cathepsins may be one of the
      determinants of the metastatic route. To the authors' knowledge, this is the
      first report on specific proteases concerning the mode of metastasis, and the
      results of this study suggest that therapeutic strategies for early stage gastric
      carcinoma might need to be changed according to the status of cathepsins.

PMID- 10931447
TI  - Vascular endothelial growth factor is an in vivo survival factor for tumor
      endothelium in a murine model of colorectal carcinoma liver metastases.
AB  - BACKGROUND: Recent studies have suggested that vascular endothelial growth factor
      (VEGF), in addition to its proangiogenic properties, also functions as a survival
      factor for endothelial cells. The authors hypothesized that inhibition of VEGF
      activity by blockade of VEGF receptor-2 (R-2) function prevents angiogenesis and
      decreases tumor growth in colon carcinoma liver metastases. METHODS: Spleens of
      mice were injected with human colon carcinoma cells producing liver metastases.
      After 7 days of tumor growth, groups of mice received either antibody to VEGFR-2
      (DC101) or phosphate-buffered saline (control). In a follow-up experiment, a
      similar treatment regimen was followed except that mice were sacrificed at 1-week
      intervals to assess the time course of endothelial cell and tumor cell apoptosis.
      RESULTS: After 21 days of therapy, the authors observed a significant decrease in
      vessel counts in liver metastases from human colon carcinoma in nude mice after
      therapy with VEGFR-2 antibody. Tumor cell apoptosis was increased significantly
      in the tumors of mice receiving DC101. Temporal studies with immunofluorescent
      double staining for the microvasculature and apoptotic cells revealed an increase
      in endothelial cell apoptosis that preceded an increase in tumor cell apoptosis.
      In vitro, treatment of human umbilical vein endothelial cells with antibody to
      VEGFR-2 produced a > 2.5-fold increase in endothelial cell apoptosis.
      CONCLUSIONS: Therapy targeting the VEGFR-2 inhibited tumor growth in a murine
      model of colon carcinoma liver metastasis. Surprisingly, this therapy did not
      only inhibit angiogenesis but also led to endothelial cell death. These findings
      suggest that VEGF, via VEGFR-2 signaling, functions as a survival factor for
      tumor endothelial cells in liver metastases from colon carcinoma.

PMID- 10931448
TI  - Different risk factors and prognosis for early and late intrahepatic recurrence
      after resection of hepatocellular carcinoma.
AB  - BACKGROUND: Recent studies have shown that the prognosis of recurrent
      hepatocellular carcinoma (HCC) after resection was dependent on the time of
      recurrence. The current study investigated whether early and late intrahepatic
      recurrences were associated with different risk factors and prognostic factors.
      METHODS: After curative resection of HCC, 246 patients were followed
      prospectively for recurrence. Intrahepatic recurrences were classified into early
      (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and
      prognostic factors for survival after recurrence in each group were analyzed.
      RESULTS: Early and late intrahepatic recurrences developed in 80 patients and 46
      patients, respectively. By multivariate analysis, preoperative tumor rupture (P =
      0.022) and venous invasion (P < 0.001) were independent risk factors for early
      recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor
      for late recurrence. By comparing histologic features of resected recurrent and
      primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as
      intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were
      multicentric occurrences. Despite similar treatments, the prognosis for patients
      with early recurrence was worse than that of patients with late recurrence
      (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent
      prognostic factors for early recurrence were serum albumin level and initial
      tumor pTNM classification, whereas only serum bilirubin level was found to be an
      independent prognostic factor for late recurrence. CONCLUSIONS: Early and late
      intrahepatic recurrences after resection of HCC were associated with different
      risk factors and prognostic factors. Early recurrences appear to arise mainly
      from intrahepatic metastases, whereas late recurrences are more likely to be
      multicentric in origin. The current study suggests that different strategies may
      be needed for the prevention and management of early and late recurrences.
      Further studies based on genetic analysis of clonal origins of tumors are
      required to clarify fully the mechanism of early and late recurrences after
      resection of HCC.

PMID- 10931449
TI  - Noninvasive and minimally invasive papillary carcinomas of the extrahepatic bile
      ducts.
AB  - BACKGROUND: Adenocarcinomas of the extrahepatic bile ducts (EBD) are uncommon
      neoplasms that are morphologically heterogenous and associated with a poor
      prognosis. Papillary carcinomas of the EBD, however, appear to follow a much less
      aggressive clinical course. METHODS: The authors reviewed the clinical records of
      nine patients with papillary carcinoma of the EBD, analyzed the microscopic
      features, and selected immunohistochemical reactivity (p53 and MIB-1) that might
      correlate with patient survival. RESULTS: Six patients were male and three were
      female, with a mean age of 65 years (range, 48-83 years). The clinical
      presentation of disease in these patients was similar to that reported for
      conventional adenocarcinoma of EBD. According to their cell phenotypes, these
      papillary carcinomas were classified as biliary type (7 cases) and intestinal
      type (2 cases). Most were located in the common bile duct and were well
      differentiated (7 cases). Five showed minimal expansile invasion into the ductal
      wall and four were noninvasive. Five patients were treated with a Whipple
      operation, three underwent segmental resections, and one underwent a left hepatic
      lobectomy. One patient died of unrelated causes 16 years after a Whipple
      operation, and another died of postoperative complications. The remaining 7
      patients are alive and disease free 1-13 years after surgery. CONCLUSIONS:
      Noninvasive and minimally invasive papillary carcinomas of the EBD are associated
      with excellent long term prognosis regardless of their cytologic features or
      their immunohistochemical reactivity to p53 and MIB-1. These tumors should be
      distinguished from biliary papillomatosis, intraductal papillary mucinous
      carcinomas of the pancreas extending into the bile ducts, papillary adenomas, and
      papillary hyperplasia.

PMID- 10931450
TI  - Treatment of patients with advanced nonsmall cell lung carcinoma using docetaxel
      and gemcitabine plus granulocyte-colony stimulating factor.
AB  - BACKGROUND: A combination regimen comprised of docetaxel, gemcitabine, and
      granulocyte-colony stimulating factor (G-CSF) was studied in patients with
      advanced nonsmall cell lung carcinoma (NSCLC) to determine its antitumor efficacy
      and tolerance. METHODS: Thirty-four patients with advanced measurable NSCLC (3
      patients with Stage IIIB and 31 patients with Stage IV disease) were treated with
      an intravenous combination chemotherapy regimen comprised of docetaxel, 80
      mg/m(2), on Day 1 and gemcitabine, 1000 mg/m(2), on Days 1 and 10; G-CSF, 5
      microg/kg, was administered subcutaneously between Days 2 and 8. Treatment cycles
      were repeated every 3 weeks. All patients were evaluable for toxicity and
      response assessment. A total of 163 courses was administered. RESULTS: Objective
      tumor response was noted in 17 patients (50%; 95% confidence interval, 32. 5
      67.5%), including 2 complete responses (6%) and 15 partial responses (44%). There
      was no change in 10 patients (29%) and 7 patients developed progressive disease.
      The median duration of response was 6.5 months (range, 3-15 months) and the
      median time to disease progression for all patients was 6.8 months (range, 1.8-18
      months). The median overall survival time was 13.0 months (range, 2. 5-23+
      months) with a 1-year survival rate of 55.8%. Myelosuppression was the most
      frequently encountered adverse reaction, although World Health Organization Grade
      3 or 4 leukocytopenia and/or granulocytopenia occurred in only 18% and 24% of
      patients, respectively. Other toxicities generally were mild to moderate, and
      always fully reversible. CONCLUSIONS: With a response rate of 50% and a median
      survival time of 13 months, the drug combination described in the current study
      appears to have significant activity against advanced metastatic NSCLC. Due to
      its fairly good tolerance and ease of administration, further investigation of
      this regimen appears warranted.

PMID- 10931451
TI  - Prognostic factors for patients with small cell lung carcinoma: analysis of a
      series of 763 patients included in 4 consecutive prospective trials with a
      minimum follow-up of 5 years.
AB  - BACKGROUND: The purposes of this study were to identify prognostic factors for
      response to chemotherapy, overall survival, and long term survival of patients
      with small cell lung carcinoma and to construct a classification of patients on
      the basis of their expected overall survival. METHODS: In the 763 patients
      registered in 4 consecutive clinical trials conducted by the European Lung Cancer
      Working Party from 1982 to 1993, the impact of 21 pretreatment variables
      assessable in a routine practice was analyzed for the various outcomes with a
      minimum follow-up of 5 years. RESULTS: The key prognostic role of disease extent
      was confirmed for all the outcomes. Additional independent prognostic factors for
      response to chemotherapy were gender, neutrophil count, and hemoglobin level; for
      overall survival, these factors were Karnofsky performance status, gender, and
      neutrophil count. Recursive partitioning and amalgamation algorithms (RECPAM)
      analysis classified patients into 4 groups, taking into consideration disease
      extent, Karnofsky performance status, age, gender, and neutrophil count. Median
      survival times for the 4 groups were 60, 47, 36, and 28 weeks, respectively. For
      long term survival, defined as a minimum survival of 2 years (9% of the
      patients), Karnofsky performance status was the only independent predictive
      factor, along with the achievement of a complete response (if this was taken into
      consideration). Small cell lung carcinoma remained the main cause of death among
      these patients. Cure was infrequent, with only 14 patients alive and disease free
      at 5 years (1.8%). CONCLUSIONS: In this study the long term prognosis associated
      with small cell lung carcinoma was poor. The well-known prognostic values of
      disease extent and Karnofsky performance status were confirmed, but the authors
      also identified age and gender (which are more controversial) as independent
      characteristics, in addition to citing the role of complete response in the
      attainment of long term survival. The independent role of neutrophils observed by
      the authors. must be validated by further studies.

PMID- 10931452
TI  - Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel
      and dose-escalating conformal thoracic radiation therapy in unresectable stage
      IIIA/B nonsmall cell lung carcinoma: a modified Phase I trial.
AB  - BACKGROUND: A modified Phase I trial was conducted evaluating the incorporation
      of 3-dimensional conformal radiation therapy (3DCRT) into a strategy of
      sequential and concurrent carboplatin/paclitaxel in Stage III, unresectable
      nonsmall cell lung carcinoma (NSCLC). In addition, dose escalation of thoracic
      conformal radiation therapy (TCRT) from 60 to 74 gray (Gy) was performed.
      Endpoints included response rate, toxicity, and survival. METHODS: Twenty-nine
      patients with unresectable Stage III NSCLC were included. Patients received 2
      cycles of induction carboplatin (AUC 6) and paclitaxel (225 mg/m(2)/3 hours)
      every 21 days. On Day 43, concurrent TCRT and weekly (x6) carboplatin (AUC 2) and
      paclitaxel (45 mg/m(2)/3 hours) was initiated. The TCRT dose was escalated from
      60 to 74 Gy in 4 cohorts. RESULTS: The response rate to induction
      carboplatin/paclitaxel was 52%. Three patients (10%) experienced disease
      progression during the induction phase. No dose-limiting toxicity was seen during
      the escalation of the TCRT dose from 60 to 74 Gy. The major toxicity was
      esophagitis, with 18% of patients developing Radiation Therapy Oncology Group
      Grade 3 esophagitis. The overall response rate was 70% (1 complete response and
      18 partial responses). Survival rates at 1 and 2 years were 69% and 45%, with a
      median survival of 21 months. The 1-year progression free survival probability
      was 41% (95% confidence interval, 23-59%). CONCLUSIONS: Incorporation of 3DCRT
      with sequential and concurrent carboplatin/paclitaxel is feasible, and dose
      escalation of TCRT to 74 Gy is possible with acceptable toxicity. Overall
      response and survival rates are encouraging. Accrual is continuing in a Phase II
      fashion at 74 Gy with sequential and concurrent carboplatin/paclitaxel.

PMID- 10931453
TI  - A phase II study of gemcitabine plus oral etoposide in the treatment of patients
      with advanced nonsmall cell lung carcinoma.
AB  - BACKGROUND: The authors have designed a non-cisplatin-based chemotherapy regimen
      for the treatment of patients with advanced nonsmall cell lung carcinoma (NSCLC).
      This regimen capitalizes on the mild toxicity of gemcitabine, a novel nucleoside
      analog. METHODS: A total of 46 chemotherapy-naive patients with histologically
      confirmed Stage IIIB or IV NSCLC were enrolled. Eligible patients were treated
      with gemcitabine 1000 mg/m(2) on Days 1, 8, and 15, plus oral etoposide 50 mg
      daily for 14 days, which was increased to 21 days if there was no World Health
      Organization (WHO) Grade 3 or 4 toxicity in the 1st 2 cycles (each cycle was 28
      days long). All patients were included for analysis of response and survival
      according to an intention-to-treat principle. RESULTS: The overall response rate
      was 43.5% (95% confidence interval [CI], 30. 7-60.2%). There was 1 complete
      response (2.2%) and 19 partial responses (41.3%). The median survival was 48.0
      weeks (95% CI, 38. 1-75.9 weeks) and the 1-year survival rate was 45% (95% CI, 29
      62%). The median time to progression for all patients was 39.2 weeks (95% CI,
      35.7-49.7 weeks). World Health Organization (WHO) Grade 3 and 4 anemia,
      neutropenia, and thrombocytopenia was reported in 29%, 32%, and 18% of patients,
      respectively. Two patients had reactivation of hepatitis B viral infection that
      resulted in WHO Grade 4 hepatic dysfunction. Other nonhematologic toxicities were
      uncommon. CONCLUSIONS: This non-cisplatin-based regimen of gemcitabine and oral
      etoposide achieved a high response and survival rate. Toxicity appeared to be
      less severe than that associated with existing cisplatin-based regimens. A
      randomized study of this regimen versus a cisplatin-based regimen is indicated.

PMID- 10931454
TI  - Hyperfunction of neutrophils in a patient with BCR/ABL negative chronic myeloid
      leukemia: a case report with in vitro studies.
AB  - BACKGROUND: Among patients diagnosed with chronic myeloid leukemia (CML), a small
      percentage lack a BCR/ABL fusion gene, a landmark of CML. Their clinical features
      are distinct from patients with BCR/ABL positive CML, although to the authors'
      knowledge the pathogenesis to date has been unknown. METHODS: A 50-year-old
      female patient with BCR/ABL negative CML and multiple complications of Graves
      disease, Sweet syndrome, and a fatal pulmonary alveolar proteinosis (PAP) is
      described in the current study. To show a clonal origin of her myeloid cells,
      hypoxanthine phosphoribosyltransferase (HPRT) assay was applied. Because the
      patient developed a progressive and fatal neutrophilia, a screening of cell
      functions in neutrophilic lineage, including in vitro colony assay of her bone
      marrow cells and production of superoxide and interleukin-8 (IL-8) by blood
      neutrophils was performed. RESULTS: Southern blot analysis based on the
      polymorphism of the HPRT gene was compatible with monoclonality of her
      neutrophils. The patient had an increased amount of bone marrow granulocyte
      macrophage progenitor cells, which formed colonies in response to a very low dose
      (0.1 ng/mL) of granulocyte-colony stimulating factor. In vitro production of
      superoxide and IL-8, which is an inducer of positive chemotaxis of neutrophils,
      by her peripheral neutrophils was markedly augmented. Her bronchoalveolar lavage
      fluid also contained a significant amount of IL-8 as well as an unusual
      infiltration of neutrophils. CONCLUSIONS: In the patient in the current study,
      hyperfunction of the neutrophils might have contributed to the onset of PAP as
      well as Sweet syndrome and to the pathogenesis of BCR/ABL negative CML.

PMID- 10931455
TI  - Patterns of breast carcinoma treatment in older women: patient preference and
      clinical and physical influences.
AB  - BACKGROUND: Older women have high rates of breast carcinoma, and there are
      substantial variations in the patterns of care for this population group.
      METHODS: The authors studied 718 breast carcinoma patients age 67 years and older
      who were diagnosed with localized disease between 1995 and 1997 from 29 hospitals
      in 5 regions. Data were collected from patients, charts, and surgeons. Logistic
      regression analysis was used to evaluate determinants of treatment. RESULTS:
      Women who were concerned about body image were 1.8 times more likely (95%
      confidence interval [95% CI], 1.1-2.8) to receive breast conservation surgery and
      radiotherapy than women without this preference, controlling for other factors.
      In contrast, women who preferred receiving no therapy beyond surgery were 3.9
      times more likely (95% CI, 2.9-6.1) to undergo mastectomy than other women, after
      considering other factors. Radiotherapy was omitted after breast conservation 3.4
      times more often (95% CI, 2.0-5.6) among women age 80 years and older than among
      women ages 67-79 years, controlling for covariates. Black women tended to have
      radiotherapy omitted after breast conservation surgery 2.0 times more often (95%
      CI, 0.9-4.4) than white women (P = 0.09). Women age 80 years and older also were
      70% less likely (odds ratio = 0.3; 95% CI, 0.1-0.8) to receive chemotherapy than
      women ages 67-79 years, controlling for health, functional status, and other
      covariates. CONCLUSIONS: After considering other factors, patient preferences and
      age were found to be associated with breast carcinoma treatment patterns in older
      women. Further research and training are needed to provide care for the growing
      population of older women that is both clinically appropriate and consonant with
      a woman's preferences.

PMID- 10931456
TI  - Pathologic features associated with nonsentinel lymph node metastases in patients
      with metastatic breast carcinoma in a sentinel lymph node.
AB  - BACKGROUND: To the authors' knowledge it has not yet been determined which
      patients with primary breast carcinoma and an axillary sentinel lymph node (SN)
      metastasis have additional metastases in nonsentinel lymph nodes. METHODS:
      Pathologic features of the primary breast carcinoma and its SN metastasis were
      examined in 194 patients and correlated with the tumor status of the non-SNs in
      the same axillary basin. Two-level cytokeratin immunohistochemistry was applied
      to the SNs and to non-SNs of cases that were negative by standard hematoxylin and
      eosin examination. RESULTS: Lymph node staging based on SN findings, size of the
      primary tumor, and presence of peritumoral lymphatic vascular invasion (LVI) were
      associated with non-SN metastasis. The majority (63%) of the 101 patients with SN
      macrometastases had non-SN metastases. Extranodal hilar tissue invasion in
      conjunction with SN involvement also was strongly associated with non-SN
      metastasis (P = 0.0001) but was present in only 65% of patients (35 of 54
      patients) with non-SN macrometastases. Approximately 26% of patients (24 of 93
      patients) with SN micrometastases (</= 2.0 mm) had non-SN metastases; among these
      patients only primary tumor size and peritumoral LVI were correlated with non-SN
      metastasis. CONCLUSIONS: Detailed pathologic examination of the primary tumor and
      its SN metastasis may increase precision in the selection of patients for further
      axillary surgery or radiation therapy.

PMID- 10931457
TI  - Usefulness of mass screening for ovarian carcinoma using transvaginal
      ultrasonography.
AB  - BACKGROUND: International Federation of Gynecology and Obstetrics Stage I ovarian
      carcinoma, which has the worst prognosis among all types of gynecologic
      carcinoma, has a high cure rate as has been reported, but early diagnosis is
      difficult and to the authors' knowledge screening methods have not been
      established. Since 1989, the authors have performed transvaginal ultrasonography
      (TVS) as a form of screening for ovarian carcinoma. The purpose of the current
      study was to summarize and evaluate screening results for the last 10 years with
      respect to ovarian carcinoma diagnosis and risk factors. METHODS: Primary
      screening by TVS was performed in asymptomatic women who participated in annual
      uterine cervical carcinoma screening. Four scanning sections by TVS were
      established and all sonograms were recorded. Women with abnormal sonograms (a
      mass > 30 mm in greatest dimension or a mass with a mixed pattern) received
      secondary screening and closer examination with a tumor marker and an imaging
      diagnostic examination. Laparotomy was conducted on all masses with a greatest
      dimension of >/= 60 mm or on suspected malignant masses. Subject information
      related risk factors also were recorded. RESULTS: Subjects were 183,034 women who
      participated in primary screening. Of these women, 51,550 were undergoing
      screening for the first time. The time required for primary screening was 1
      minute per subject. Secondary screening was required for 5309 participants
      (10.3%) and surgery was performed on 324 participants. Twenty-two primary tumors
      and 2 metastatic tumors were detected for a diagnostic rate of 0.047%. Of the 22
      primary tumors, 17 (77.3%) were classified as Stage I carcinoma, with tumor
      markers positive only for 5 (29.4%). The percentage of the total number of Stage
      I ovarian carcinoma cases increased after the induction of screening from 29.7%
      to 58.8%. CONCLUSIONS: These results are significant in that 77.3% of the primary
      ovarian carcinomas found during the current screening were of curable Stage I.
      Increased use of TVS screening for ovarian carcinoma may increase the chance for
      early diagnosis and decrease the mortality of the disease.

PMID- 10931458
TI  - Expression of cyclooxygenase-2 in prostate carcinoma.
AB  - BACKGROUND: Nonsteroidal antiinflammatory drugs inhibiting cyclooxygenase (COX)
      enzyme activity in both its constitutive (COX-1) and inducible (COX-2) isoforms
      were shown also to inhibit the development of colon carcinoma in animal models.
      COX-2 is an inducer of angiogenesis of new blood vessels. The expression of COX-1
      and COX-2 in prostate tissues from patients with prostate carcinoma was
      investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) and
      immunohistochemistry. METHODS: Tumor specimens were obtained from 28 prostate
      carcinoma (PC) patients, 8 benign prostatic hyperplasia (BPH) patients, 1
      prostatic intraepithelial neoplasia (PIN) patient, and 8 specimens of normal
      prostate tissue (NP). Affinity-purified COX-1 and COX-2 antibodies were used in
      immunochemistry. RESULTS: Very weak expression of COX-1 and marked expression of
      immunoreactive COX-2 in tumor cells was obtained. In contrast, expression of both
      isoforms was very weak in all cases of BPH and in the NP tissues. Immunoreactive
      COX-1 also was very weak in all cases of benign tissues. The extent and intensity
      of immunoreactive COX-2 polypeptides in tumor cells was statistically much
      greater than those of cells from BPH. Immunostaining with normal rabbit
      immunoglobulin G was completely negative. By RT-PCR analysis, enhanced expression
      of COX-2, but not COX-1, was observed in PC tissue. BPH displayed faint
      expression of COX-2. CONCLUSIONS: The results of the current study demonstrated
      that human prostate carcinoma cells generated COX-2, and that COX-2 might play an
      important role in the proliferation of prostate carcinoma cells. These findings
      suggest that inhibition of COX-2 development may lead not only to inhibition of
      the proliferation and metastasis of prostate carcinoma but also to the inhibition
      of prostate carcinogenesis.

PMID- 10931460
TI  - Prognostic utility of the recently recommended histologic classification and
      revised TNM staging system of renal cell carcinoma: a Swiss experience with 588
      tumors.
AB  - BACKGROUND: A new, internationally accepted histologic classification of renal
      cell carcinoma (RCC) and a new edition of the TNM staging system were introduced
      in 1997. In the latter, there was a dramatic change in the pT classification of
      organ-confined renal cancer in which the break point between category pT1 and pT2
      was increased from 2.5 cm to 7 cm. METHODS: To study the significance of the new
      pT classification and the new recommendations for histologic classification, 588
      nephrectomy specimens were reevaluated to define morphologic prognostic
      parameters in RCC. pT classification (TNM 1997), histologic subtype, histologic
      tumor grade, presence of necrosis, and sarcomatoid differentiation were assessed.
      RESULTS: The histopathologic review according to the new classification revealed
      487 conventional (clear cell) (83%), 64 papillary (11%), 31 chromophobe (5%), and
      6 collecting duct (1%) RCCs. Clinical follow-up was available for 470 RCCs. The
      new pT classification (1997) was strongly correlated with patient survival (P <
      0.0001). Histologic grade, presence of necrosis, and sarcomatoid differentiation
      provided independent prognostic information on the clear cell subtype of renal
      cancer. Sarcomatoid differentiation, but not tumor necrosis, portended a dismal
      prognosis for patients with papillary RCC. Chromophobe RCC was associated with a
      significantly better prognosis than clear cell RCC (P = 0.05). Papillary RCC with
      scanty cytoplasm and small cells (type 1) behaved less aggressively than
      papillary tumors with eosinophilic cytoplasm and large cells (type 2; P < 0.001).
      CONCLUSIONS: Accurate histologic classification according to the new
      recommendations has implications because the prognostic importance of other
      histologic features that are of independent significance varies with tumor
      subtype. The data suggest that the new pT classification allows good separation
      of prognostic groups of patients with renal cancer.

PMID- 10931459
TI  - Infusional interleukin-2 and 5-fluorouracil with subcutaneous interferon-alpha
      for the treatment of patients with advanced renal cell carcinoma: a southwest
      oncology group Phase II study.
AB  - BACKGROUND: A Phase II trial was conducted to determine the response rate of
      patients with advanced renal cell carcinoma to a three-drug combination of 5
      fluorouracil (5-FU), interleukin-2 (IL-2), and interferon-alpha-2b (IFN-alpha).
      METHODS: A 2-stage accrual plan was used that was designed to determine whether
      response to this regimen was consistent with a true response rate of >/= 30%. The
      regimen was comprised of 5 treatment days weekly for 4 weeks every 6 weeks. Each
      weekly treatment was comprised of 5-FU, 1750 mg/m(2), continuous intravenous
      (i.v.) infusion over 24 hours followed by IL-2, 6 MIU/m(2)/day, continuous i.v.
      infusion for 4 days. IFN-alpha, 6 MU/m(2), was given subcutaneously on Days 1, 2,
      and 5. RESULTS: Thirty-eight patients were entered on study, 3 of whom were
      ineligible. Among the 35 eligible patients there were 3 confirmed partial
      responses (PR) and 1 complete response (CR), for an overall response rate of 11%
      (95% confidence interval, 3-27%). One patient considered as having a PR had
      minimal evidence of residual disease and was free from disease progression at >
      2.5 years of follow-up, as was the patient with CR. Three additional patients not
      qualified as having a PR were showing signs of response at the time they were
      removed from protocol, and another patient who was removed from protocol early
      for management of an infection subsequently responded to the same regimen off
      protocol. Thirteen patients were considered nonassessable (NASS) for response,
      many of whom had multiple poor risk features and were unable to complete 1 cycle
      of treatment. CONCLUSIONS: This multicenter study failed to confirm an
      advantageous overall response rate for this three-drug regimen. However, there
      were two durable responses and indications of responsiveness not scored as PRs
      among patients with more favorable risk factor patterns, and many poor risk NASS
      patients. For these reasons, the response rate reported in the current study may
      be a conservative reflection of the effectiveness of this regimen.

PMID- 10931461
TI  - A Phase II trial of bryostatin-1 for patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: Patients with metastatic renal cell carcinoma have a poor prognosis
      and no standard therapy is available. The authors performed a Phase II trial of
      the novel agent bryostatin-1 in this patient population. METHODS: In all, 30
      patients with measurable, previously untreated metastatic renal cell carcinoma
      were studied. Patients had excellent physiologic reserve and preserved
      performance status. Bryostatin-1 (25 microg/m(2)) was given in the PET
      (polyethyleneglycol, ethanol, and Tween 80) formulation as a 30-minute
      intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. In general,
      treatment was continued until disease progression. RESULTS: Two patients had
      significant objective responses, although methodologic problems made
      interpretation difficult. The median time to progression for all patients was 2.1
      months; the median overall survival was 13.1 months. The treatment was generally
      well tolerated. Myalgia was the most common adverse event. One patient died while
      on study. This was a sudden death for a patient receiving a 15th cycle of
      therapy. Aside from this patient (for whom the correlation of study drug to death
      was not clear), no Grade 4 nonhematologic toxicity was encountered in more than
      150 treatment courses delivered. CONCLUSIONS: There is minimal, if any,
      clinically relevant single-agent activity of bryostatin-1 at this dose and
      schedule for patients with metastatic renal cell carcinoma.

PMID- 10931462
TI  - Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally
      advanced bladder carcinoma.
AB  - BACKGROUND: The aim of this study was to elucidate the associations among
      immunostaining for p53, p21, and mdm2; their respective expression within each
      tumor; and the value of these variables for predicting treatment outcome after
      cystectomy for patients with locally advanced bladder carcinoma. METHODS: The
      hospital records from all 173 patients treated with cystectomy for locally
      advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively
      reviewed. Three consecutive sections from biopsies taken before any treatment
      were stained using the standard immunohistochemical technique for p53, p21, and
      mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression
      and 10% or more for positive p21 and mdm2 expression. RESULTS: Positive
      immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors
      (51%), and for mdm2 in only 16 tumors (9%). The only association found between
      immunostaining for the three antibodies was that most mdm2-positive tumors had
      positive p21 expression. Tumor mapping of regional immunostaining showed no
      association between immunostaining for p53 and p21. In a proportional hazards
      analysis, no association was found between the results of immunostaining for the
      three antibodies and treatment outcome. CONCLUSIONS: Positive or negative
      expression of p53, p21, or mdm2, or combinations of these, was not associated
      with cancer specific mortality after cystectomy for bladder carcinoma. There was
      no association between immunostaining for p21 and p53, whereas positive
      immunostaining for mdm2 was observed in a minority of the tumors. These results
      indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins
      and tumor suppressor proteins along the p53 pathway that are involved in tumor
      development and progression.

PMID- 10931463
TI  - The impact of characteristics of cigarette smoking on urinary tract cancer risk:
      a meta-analysis of epidemiologic studies.
AB  - BACKGROUND: Although narrative reviews have concluded that there is strong
      support for an association between cigarette smoking and urinary tract cancer,
      the association has never been quantified systematically in reviews. The purpose
      of this systematic review was to summarize and quantify the impact of different
      smoking characteristics (status, amount, duration, cessation, and age at first
      exposure) both unadjusted and adjusted for age and gender. METHODS: The authors
      included 43 epidemiologic studies (8 cohort and 35 case-control) and calculated
      summary odds ratios (SORs) by meta-regression analyses for different smoking
      characteristics. They also evaluated changes in summary estimates according to
      differences in study methodology. RESULTS: Smoking status and increased amount
      and duration of smoking were associated with a strong increased risk of urinary
      tract cancer. Smoking cessation and age at first exposure were negatively
      associated with the risk of urinary tract cancer. The age- and gender-adjusted
      SORs for current and former cigarette smokers compared with those for nonsmokers
      were 3.33 (95% confidence interval [CI], 2.63-4.21) and 1.98 (CI, 1.72-2.29),
      respectively. Even though the component studies differed in methodology, the
      results were rather consistent. CONCLUSIONS: The results suggest a substantial
      increase in risk of cancer of the urinary tract for cigarette smokers. Based on
      the results of this study and previous literature, the authors conclude that
      current cigarette smokers have an approximately threefold higher risk of urinary
      tract cancer than nonsmokers. In Europe, approximately half of urinary tract
      cancer cases among males and one-third of cases among females might be
      attributable to cigarette smoking.

PMID- 10931464
TI  - The risk of venous thromboembolism is increased throughout the course of
      malignant glioma: an evidence-based review.
AB  - BACKGROUND: Venous thromboembolism (VTE) frequently complicates the course of
      patients with cancer, and there is evidence to suggest that patients with brain
      tumors are at particularly high risk. The objective of this methodology-based
      literature review was to quantify the rate of incidence of VTE in patients with
      malignant glioma and to determine the factors that predict an increased risk of
      this complication. METHODS: Studies meeting predefined inclusion criteria were
      evaluated independently on an eight-item methodology index by three raters.
      Authors were contacted to resolve ambiguities. The results of the studies were
      summarized and the incidence rate of VTE within the early postoperative phase and
      during extended follow-up were reported separately. RESULTS: Within 6 weeks after
      surgery the incidence rate of deep venous thrombosis (DVT) ranged from 3% to 60%,
      varying with the prophylaxis regimen used, the method of diagnosis, and the study
      design. Beyond 6 weeks postoperatively, the rates of DVT ranged from 0.013 to
      0.023 per patient-month of follow-up. The single study with no significant
      methodologic deficiencies found a 24% rate of incidence of symptomatic DVT over
      the 17 months of follow-up beyond the first 6 postoperative weeks. In 6 studies
      the presence of leg paresis, histologic diagnosis of glioblastoma multiform, age
      >/= 60 years, large tumor size, use of chemotherapy, and length of surgery > 4
      hours were identified as possible risk factors. CONCLUSIONS: The incidence of VTE
      is high throughout the course of malignant glioma. A randomized, controlled trial
      is needed to clarify whether the benefits of long term anticoagulant prophylaxis
      outweigh the risks and costs of such therapy.

PMID- 10931465
TI  - Image-guided core-needle biopsy in patients with suspected or recurrent
      lymphomas.
AB  - BACKGROUND: It is now commonly admitted that the diagnosis of recurrence of
      lymphoma can be assessed by image-guided needle biopsy (IGNB). However, the means
      of obtaining tissue for the original diagnosis of lymphoma is often surgery. The
      aim of this study was to compare the accuracy of IGNB at the time of diagnosis
      and at the time of recurrence or progression. METHODS: The authors performed 212
      IGNBs on 194 patients who eventually had a diagnosis of lymphoma. One hundred
      three IGNBs were obtained at original diagnosis and 109 at recurrence or
      progression. Large-cutting core-biopsy needles, ranging in size from 20 gauge to
      14 gauge, were used. Immunohistochemistry studies were performed in all lymphoma
      cases. RESULTS: A diagnosis of lymphoma with subtyping was obtained in 88% of all
      cases, in 85% at initial diagnosis, and in 89% at follow-up. Therapy was
      initiated on the basis of IGNB in 93% of all cases, in 91% at initial diagnosis,
      and in 94% at follow-up. Benign complications occurred in 7.5% of cases and did
      not require specific treatment. IGNB was equally effective for making a specific
      diagnosis of lymphoma and initiating therapy at the time of original diagnosis
      and at follow-up. CONCLUSIONS: The authors recommend that IGNB be performed as
      the initial procedure for the diagnosis of lymphoma in the absence of peripheral
      lymph nodes, either at presentation or at recurrence.

PMID- 10931466
TI  - Cancer incidence in Abidjan, Ivory Coast: first results from the cancer registry,
      1995-1997.
AB  - BACKGROUND: There are few data concerning cancer incidence rates in contemporary
      West Africa. The first data from the cancer registry of Abidjan, the capital of
      Ivory Coast, for the period 1995-1997 are reported in the current study. METHODS:
      The cancer registry attempts to record data on all new cases of cancer diagnosed
      in the city of Abidjan, including cases without histologic confirmation of
      diagnosis. RESULTS: Two thousand eight hundred fifteen new cancer cases were
      registered in 3 years, corresponding to age-standardized (world population)
      incidence rates of 83.7 per 100,000 in men and 98. 6 per 100,000 in women. As
      reported elsewhere in West Africa, the principal cancers in men were liver cancer
      (15%) and prostate cancer (15.8%), with modest rates of non-Hodgkin lymphoma
      (10.5%) and gastric cancer (4.5%). In women, breast cancer was the most frequent
      tumor (25.7%), followed by cervical cancer (24.0%) and non-Hodgkin lymphoma
      (7.3%). In contrast to other registry data from West Africa, Kaposi sarcoma
      occurs with moderate frequency (7.7% of cases reported in men and 2.1% in women).
      In the pediatric age group, relatively high incidence rates were found for
      Burkitt lymphoma. CONCLUSIONS: Although there most likely is some
      underascertainment of cases, so that the actual incidence rates may be
      underestimated, the cancer profile should be a fair reflection of the true
      situation. In addition to tumors that are well known to be common in sub-Saharan
      Africa, such as cancers of the liver and cervix, this urban population shows some
      features of "Westernization" of cancer patterns, in particular the relatively
      high rates of breast cancer and prostate cancer. The effects of the acquired
      immunodeficiency syndrome epidemic are reflected in the moderate rates of Kaposi
      sarcoma reported.

PMID- 10931467
TI  - Follicular dendritic cell sarcoma of the neck: report of two cases complicated by
      pulmonary metastases.
AB  - BACKGROUND: Follicular dendritic cell (FDC) sarcoma is an uncommon neoplasm
      occurring primarily in lymph nodes but also in extranodal sites. A correct
      diagnosis can be difficult to make, especially in the latter sites. METHODS: Two
      patients with FDC sarcoma of the cervical soft tissues that metastasized to the
      lungs are reported. Both were initially misdiagnosed as having CASTLE (carcinoma
      showing a thymus-like element). Additional immunohistochemical stains were
      performed. RESULTS: The primary tumors showed jigsaw puzzle-like lobulation
      resembling thymic epithelial tumor and consisted of spindly cells arranged in
      fascicles, whorls, and a storiform pattern. The spindly cells had indistinct cell
      borders, vesicular nuclei, and distinct nucleoli. Perivascular spaces were
      present. Lymphocytes were sprinkled throughout the tumor in one case but were
      sparse in the other. The metastatic deposits in the lungs appeared 27 and 2
      years, respectively, after the initial presentation and were histologically
      similar to the original tumors. The FDC nature of the primary and metastatic
      tumors was confirmed by positive staining with CD21/CD35 cocktail and CD23 and by
      negative staining for cytokeratin. In one case, in direct continuity with the
      main tumor, there was a lobulated lesion composed of small lymphocytes punctuated
      by large cells with vesicular nuclei, histologically reminiscent of thymoma. The
      large cells were shown by immunohistochemistry to represent FDCs forming complex
      interconnecting meshworks. It is unclear whether this contiguous mass represents
      a precursor lesion or an unusual-looking component of the neoplasm. CONCLUSIONS:
      FDC sarcoma can look deceptively like a thymic epithelial tumor histologically. A
      correct diagnosis requires a high index of suspicion and immunohistochemical
      evaluation. The tumor shows a propensity to metastasize to the lungs, which can
      be delayed until more than 20 years after initial presentation.

PMID- 10931468
TI  - Expression of cyclin E in placentas with hydropic change and gestational
      trophoblastic diseases: implications for the malignant transformation of
      trophoblasts.
AB  - BACKGROUND: Although much is known about the morphologic, cytogenetic, and
      clinical characters of gestational trophoblastic diseases, little information has
      appeared concerning the parameters related to their persistence or neoplastic
      transformation. Cell cycle alterations in tumor tissue were examined in this
      study in light of obvious changes in the clinical behavior of malignant cells.
      There is an increasing body of evidence suggesting that the abnormal expression
      of cyclins is considered one of the most important events in malignant
      transformation of various human cancers. Among these cell cycle regulators, the
      role of cyclin E in the neoplastic transformation of trophoblast populations has
      been poorly defined. METHODS: Using formalin fixed, paraffin embedded
      trophoblastic tissues, the authors investigated the expression of cyclin E by
      immunohistochemistry in placentas with hydropic change and gestational
      trophoblastic diseases. The specimens examined included tissue from 29 patients
      with complete hydatidiform mole, 18 patients with partial hydatidiform mole, and
      6 patients with choriocarcinoma after term pregnancy or abortion. The authors
      also studied four cases of hydropic abortion. RESULTS: The cyclin E indexes (CEI)
      were as follows: 25.7% +/- 6.2% for hydropic change, 35.3% +/- 12.7% for triploid
      partial moles, 42.2% +/- 13.1% for diploid/tetraploid complete moles, and 63.6%
      +/- 9.5% for choriocarcinomas. There was a significant difference in CEI between
      placentas with hydropic change and partial mole (P = 0.04) and placentas with
      hydropic change and complete mole (P = 0.003). Choriocarcinomas had significantly
      higher cyclin E expression compared with placentas, partial moles, and complete
      moles, respectively. A significant correlation between the expression of cyclin E
      and S-phase fraction was observed in gestational trophoblastic diseases (rank
      correlation coefficient = 0.45, P < 0. 05). The relation between cyclin E
      expression and proliferation was abrogated in placentas with hydropic change,
      suggesting that cyclin E up-regulation represents a genuine aberration.
      CONCLUSIONS: The results of this study were consistent with the concept that
      cyclin E overaccumulation may play an important role in the uncontrolled
      proliferation and neoplastic transformation of trophoblasts.

PMID- 10931469
TI  - High dose therapy and autologous stem cell transplantation for human
      immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly
      active antiretroviral therapy.
AB  - BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has
      allowed the exploration of more dose-intensive therapy such as autologous stem
      cell transplantation (ASCT) in selected patients with human immunodeficiency
      virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on
      the use of myeloablative chemotherapy with ASCT in two HIV positive patients with
      NHL. The first patient underwent ASCT at the time of first disease remission for
      poor risk, diffuse, large cell NHL and the second patient had multiply recurrent,
      chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a
      transplant conditioning regimen of high dose cyclophosphamide, carmustine, and
      etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive
      peripheral blood stem cells (PBSC) utilized for ASCT was collected using
      granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization
      while both patients were receiving concomitant HAART for HIV infection. HAART was
      continued during CBV conditioning. Prompt hematopoietic recovery was observed
      after ASCT. Both patients remained in clinical disease remission from their
      lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS:
      ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34
      positive PBSC can be procured from patients receiving HAART and chemotherapy for
      NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV
      myeloablative chemotherapy regimen without increased acute regimen-related
      toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of
      hematologic function and sustained engraftment after ASCT. Given the poor
      prognosis of patients with HIV-associated NHL treated with conventional
      chemotherapy, further investigation of this approach should be considered.

PMID- 10931470
TI  - Nasopharyngeal carcinoma in childhood and adolescence: a single-institution
      experience with combined therapy.
AB  - BACKGROUND: A high cure rate may be attained for locally advanced,
      undifferentiated nasopharyngeal carcinoma (NPC) in children, provided that a
      combined modality of treatment is employed. Both local and systemic therapies are
      necessary. Results at a single pediatric institution were analyzed. METHODS: From
      November 1988 to December 1997, 16 consecutive patients were treated with NPC at
      the Hospital Garrahan in Buenos Aires, Argentina. The authors were able to
      evaluate 11 patients (9 boys and 2 girls); their median age was 12 (range, 8-14)
      years. Chemotherapy consisted of 3 courses, every 3 weeks, of 5-fluorouracil (500
      mg/m(2)) plus bleomycin (15 mg/m(2)) daily for 4 days, with cisplatin (100
      mg/m(2)) added the last day. External beam radiotherapy was delivered over a
      median of 52 (range, 45-63) days, to a median cumulative dose to the primary site
      of 55 (range, 50-61.2) grays (Gy). The median dose for the lower neck area was 45
      (range, 45-55.8) Gy. All patients received radiotherapy to the primary site and
      to the initially involved lymphoid areas, with daily single doses of 1.8 Gy (5 of
      7 days per week). RESULTS: The main symptoms at onset were cervical mass (100%),
      epistaxis (54%), cephalalgia (36%), and trismus (36%). All cases were Stage IV
      (American Joint Committee on Cancer and International Union Against Cancer TNM
      system). Complete response was achieved in 45% of patients after initial
      chemotherapy. With a median follow-up of 63 (range, 23-119) months, disease free
      survival (with standard error [SE]) and overall survival estimates were 61% (16%)
      and 91% (9%), respectively, at 75 months. Acute toxicity due to therapy was
      tolerable. Chronic sinusitis (73%), hypothyroidism (73%), and mild (64%) or
      moderate (9%) neck fibrosis were detected at follow-up. CONCLUSIONS: Although
      this series is small, the authors concluded that NPC patients have a good chance
      of survival in the setting described, in spite of locally advanced disease.
      Chemotherapy might be useful in preventing the development of systemic
      metastases.

PMID- 10931471
TI  - Asian American and Pacific Islander breast and cervical carcinoma screening rates
      and healthy people 2000 objectives.
AB  - BACKGROUND: Breast carcinoma is the number one cause of cancer-related mortality
      among Asian American and Pacific Islander (AAPI) women, and for certain subgroups
      cervical carcinoma is among the top three causes. Yet AAPI women have the lowest
      cancer screening and early detection rates of all ethnic groups. The practice of
      merging AAPI data hides significant variation among AAPI groups, and the groups
      at highest risk for late presentation of disease become invisible. To the
      authors' knowledge, this study is the first report of disaggregated national data
      for breast and cervical carcinoma screening in AAPI subpopulations. The authors
      used data from the National Health Interview Survey (NHIS 1993 and 1994) and
      evaluated major socioeconomic and access variables associated with screening
      practices. METHODS: Healthy People 2000 (HP2000) criteria were used to evaluate
      the most recent NHIS screening rates for AAPIs as one group and for six distinct
      subgroups compared with HP2000 criteria. The sample included 2756 non-Hispanic
      AAPI and 64,196 non-Hispanic white women age 18 years or older in the 1993 and
      1994 NHIS. The effects of socioeconomic and access-to-care indicators on
      screening were explored. RESULTS: Breast and cervical carcinoma screening rates
      for AAPIs were below those for white women and well below national goals and
      guidelines. Lack of insurance, low income, and lack of a usual source of care had
      a significantly greater negative impact on AAPIs than on white women, indicating
      that AAPIs may be more vulnerable to structural barriers to cancer control
      efforts. CONCLUSIONS: AAPI women have very low rates of breast and cervical
      screening, which increases their chances of later stage disease presentation. To
      reach the Healthy People 2000 objectives, targeted efforts are needed to increase
      cancer screening among AAPI women overall and specific subgroups in particular.

PMID- 10931472
TI  - Brain metastasis from prostate carcinoma.

PMID- 10931473
TI  - Author reply

PMID- 10931474
TI  - Classification of isolated tumor cells and micrometastasis.

PMID- 10931475
TI  - Classification of isolated tumor cells and micrometastasis.

PMID- 10931476
TI  - Author reply

PMID- 10931478
TI  - Author reply

PMID- 10931477
TI  - 5-fluorouracil-induced small bowel toxicity in patients with colorectal
      carcinoma.

PMID- 10931479
TI  - Testicular lymphoma is associated with a high risk of extranodal recurrence.

PMID- 10931480
TI  - Author reply

PMID- 10931481
TI  - Damage to the cytoskeleton of large diameter sensory neurons and myelinated axons
      in vincristine-induced painful peripheral neuropathy in the rat.
AB  - Vincristine, along with other antimitotic chemotherapeutic drugs, produces a
      peripheral neuropathy in humans that is accompanied by painful paresthesias,
      dysesthesias, and occasionally hypoesthesia, and by hyporeflexia (Holland et al.
      [1973] Cancer Res. 33:1258-1264; McLeod and Penny [1969] J Neurol Neurosurg
      Psychiatry 32:297-304; Postma et al. [1993] J Neurooncol. 15:23-27; Sandler et
      al. [1969] Neurology 19:367-374). Systemic administration of vincristine causes
      swelling of unmyelinated axons and disorientation of axonal microtubules (Tanner
      et al. [1998a1998a] J Comp Neurol. 395:481-492) at a time when it also produces
      allodynia and mechanical hyperalgesia (Aley et al. [1996] Neuroscience 73:259
      265; Authier et al. [1999] Neuroreport 10:965-968) and enhanced responsiveness in
      C-fibers in the rat (Tanner et al. [1998b] J Neurosci. 18:6480-6491). Because
      slowing of A-fiber conduction velocities had also been demonstrated (Tanner et
      al. [1998b] J Neurosci. 18:6480-6491), and mechanical hyperalgesia can occur
      secondary to damage to large diameter sensory afferents (Basbaum et al. [1991]
      Can J Physiol Pharmacol. 69:647-651; Coggeshall et al. [1993] Pain 52:233-242;
      Woolf and Mannion [1999] Lancet 353:1959-1964), we sought to determine whether
      vincristine also induced ultrastructural changes in myelinated A-fibers.
      Moreover, since systemic treatment with vincristine did not cause profound
      microtubule depolymerization in the unmyelinated axons of the peripheral nerve,
      we hypothesized that the drug's effects may be more extensive in the cell body,
      because in the spinal ganglion, the blood-nerve barrier is less restrictive. We
      used quantitative ultrastructural methods to analyze the microtubule cytoskeleton
      in myelinated axons in the mid-shaft of the saphenous nerve and in the sensory
      ganglion cells. Vincristine induced swelling of the whole nerve and an increase
      in the cross-sectional areas of myelinated axons but no loss of myelinated axons.
      There was a significant decrease in axonal microtubules, as well as microtubule
      disorganization, in myelinated fibers from vincristine-treated rats. In the
      spinal ganglion, vincristine induced swelling of large diameter sensory neurons
      and a build-up of neurofilaments in the cell bodies and proximal axons,
      suggestive of impaired anterograde axonal transport.

PMID- 10931482
TI  - Glutamate and aspartate immunoreactivity in dorsal root ganglion cells supplying
      visceral and somatic targets and evidence for peripheral axonal transport.
AB  - Glutamate (Glu) is released by primary sensory neurons at their central synapses,
      although immunohistochemical studies have shown that only a proportion of these
      cell bodies are Glu-immunoreactive. Antisera raised against Glu or aspartate
      (Asp) were used to investigate whether neurons that store high levels of these
      substances have a unique neuropeptide content or target projection. In male rats,
      many lumbar and sacral dorsal root ganglion cells and their associated glia show
      high levels of Glu or Asp immunoreactivity, and fewer than half of these also
      express substance P or calcitonin gene-related peptide. Conversely, only a
      minority of peptide-containing neurons store high levels of excitatory amino
      acids. When neurons that were labelled retrogradely from somatic (skin,
      gastrocnemius muscle) or visceral (bladder, rectum) targets were immunostained
      for peptides or amino acids, there was some variation in the peptide expression
      of their sensory nerve supply, but there was very little or no difference in the
      prevalence of Glu- or Asp-immunoreactive neurons. In vitro studies on isolated
      lumbar dorsal root ganglia showed that, after crushing nerve roots, Glu and Asp
      were transported in both central and peripheral directions, similar to substance
      P. These studies showed that primary afferent neurons store different levels of
      Glu and Asp in their somata but that this is not correlated with their target
      tissue or peptide content. This suggests that both visceral and somatic sensory
      neurons may vary considerably in the way they release, store, or metabolise amino
      acids. Peripheral and central transport of amino acids suggests that, in some
      neurons, reuptake at the synapse may need to be supplemented by amino acids that
      are produced or accumulated in the soma.

PMID- 10931483
TI  - Nucleus ambiguus projections to cardiac ganglia of rat atria: an anterograde
      tracing study.
AB  - We injected the anterograde fluorescent tracer 1,1;-dioleyl-3,3,3;, 3;
      tetramethylindocarbocyanine methanesulfonate (DiI) into the nucleus ambiguus (NA)
      and used confocal microscopy to inventory NA fibers and axon terminals in whole
      mounts of rat atrial tissues. Both the axons projecting to cardiac ganglia and
      the innervated principal neurons (PNs) were counted. Rats were injected
      unilaterally in the NA with DiI, either at four sites (between 600 microm rostral
      and 600 microm caudal to the obex) or at nine sites (1,600 microm rostral to
      1,600 microm caudal). Fluoro-Gold was administered intraperitoneally to
      retrogradely label neurons of the dorsal motor nucleus of the vagus (DmnX), NA,
      and cardiac ganglia. To verify that the DiI-labeled fibers examined in the atria
      originated exclusively from the NA, neurons of the DmnX and the nodose ganglia
      were surveyed for DiI labeling. Our observations established that (1) NA fibers
      in the cardiac branches of the vagus numbered in the range of 82-151, left; or 60
      122, right. (2) Both left and right NA supplied substantial numbers of fibers to
      each of the three major cardiac ganglionic plexuses. (3) NA axons terminated in
      dense basket, or calyx, endings around individual PNs. (4) By issuing divergent
      collaterals, individual NA fibers supplied numerous PNs with these calyx endings.
      (5) Labeled axons innervated 2,248 (left vagus) and 1,784 (right), or at least
      56% and 45%, of the cardiac PNs. (6) Divergence (i.e., NA axons:PNs innervated)
      averaged between 1:27 (left vagus) and 1:30 (right vagus). Several features of
      these NA projections to cardiac ganglia contrasted sharply with those of DmnX
      projections that we have recently characterized with the same tracing protocol:
      (1) NA fibers did not innervate small intensely fluorescent cell clusters in
      cardiac ganglia, whereas DmnX axons did. (2) NA efferent fascicles contained more
      large fibers (presumably B-type), whereas the DmnX issued more fine caliber
      fibers (presumably C-type). (3) NA fibers diverged about three times as
      extensively as did DmnX axons. Taken together, our data strongly suggest that
      vagal control of the heart involves the convergence and integration of distinct
      NA and DmnX projections within the cardiac plexuses.

PMID- 10931484
TI  - Domain-restricted expression of two glutamic acid decarboxylase genes in
      midgestation mouse embryos.
AB  - Glutamic acid decarboxylase (GAD) is the biosynthetic enzyme for gamma
      aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central
      nervous system (CNS) of vertebrates. In addition to the adult CNS, GABA and GAD
      also have been detected in embryos, although their precise localization and
      specific functions in embryonic development have not been elucidated. In this
      paper, the authors studied the cellular distribution of two GAD isoforms, GAD65
      and GAD67, in midgestation mouse embryos by in situ hybridization histochemistry.
      With few exceptions, it was found that GAD65 and GAD67 mRNAs are localized in
      overlapping cellular domains of the embryonic CNS that later develop into regions
      with a strong GABAergic contribution. The GAD-expressing cells are situated in
      the differentiating zone of the embryonic day 10.5 (E10.5) through E11.5 CNS and
      in the subventricular zone and the mantle zone of the E12.5 CNS, which suggests
      that they are committed neuronal precursors. By using a specific serum for GABA,
      a similar pattern of distribution was obtained, indicating that GAD mRNAs are
      translated efficiently into enzymatically active GAD, which produces embryonic
      GABA. The expression domains of GAD overlap with those of genes that are known to
      be involved in the patterning of the embryonic CNS. The two GAD mRNAs also are
      detected outside of the embryonic CNS in various cell types, mainly those of
      placodal and neural crest origin. This pattern of expression is consistent with
      the notion that GAD and its product, GABA, play a signaling role during
      development.

PMID- 10931485
TI  - Widespread expression of rat collapsin response-mediated protein 4 in the
      telencephalon and other areas of the adult rat central nervous system.
AB  - The rat collapsin response-mediated protein 4 (rCRMP-4) is a member of a family
      of proteins that are involved in axonal growth. It is found transiently in
      postmitotic neurons, such as those that are generated in the adult hippocampus.
      The authors used immunocytochemistry to investigate whether areas of the rat
      central nervous system (CNS) that retain postnatal neurogenesis express this
      protein. They found pronounced rCRMP-4 immunoreactivity in recently generated
      cells in the dentate granular layer, the subventricular zone, the olfactory
      bulbs, and the rostral migratory stream, four areas in which the production or
      migration of neurons occurs in adulthood. However, rCRMP-4 immunoreactivity also
      is expressed in many other regions of the rat brain in which there is no record
      of adult neurogenesis or neuronal migration, e.g., in the olfactory glomeruli and
      in neurons of the cerebral cortex. In the hypothalamus, intensely rCRMP-4-labeled
      neurons populated the supraoptic, paraventricular, and periventricular nuclei as
      well as the median eminence and the arcuate nucleus. Immunoreactivity for rCRMP-4
      also was present in certain neurons of the interpeduncular nucleus, median raphe,
      superior colliculus, and scattered granule cerebellar neurons. Many of these
      regions are known to display axonal outgrowth and/or synaptic rearrangement in
      adulthood and to coexpress the polysialylated form of the neural cell adhesion
      molecule. Thus, the results of this study suggest that rCRMP-4 expression in the
      CNS is associated with cells that are migrating or are undergoing axonal growth.
      Nevertheless, small, rCRMP-4-immunoreactive cells were seen throughout the brain.
      These cells did not express neuronal, astroglial, or microglial markers, although
      some of them also were immunoreactive for rip antibody, suggesting an
      oligodendroglial lineage.

PMID- 10931486
TI  - Gustatory innervation and bax-dependent caspase-2: participants in the life and
      death pathways of mouse taste receptor cells.
AB  - In the adult mouse tongue, an average of 11% of the gustatory receptor cells are
      replaced each day. In investigating homeostatic cell death mechanisms in
      gustatory renewing epithelium, we observed that taste receptor cells were
      selectively immunopositive for the bcl-2 family death factor, Bax, and for the
      protease Caspase-2 (Nedd2/Ich1). We determined that 8-10% of the taste receptor
      cells of the vallate papilla were Bax positive and that 11% were Caspase-2
      positive. Some of these immunopositive taste cells had apoptotic morphological
      defects. Within the subset of vallate taste cells immunopositive for either
      Caspase-2 or Bax, up to 79% coexpressed both death factors. Bax and Caspase-2
      first appeared in occasional vallate taste receptor cells on the same postnatal
      day-the day after birth. bax null mutation markedly reduced gustatory Caspase-2
      immunoexpression. These observations suggest that taste cell death pathways
      utilize p53, Bax, and Caspase-2 to dispose of aged receptor cells. Apart from
      reducing Caspase-2 expression, Bax deficiency also altered taste organ
      development. bax(-/-) mice had a more profusely innervated vallate papilla, which
      grew to be 25% longer and taller, with the mean taste bud containing more than
      twice the normal number of taste cells. This augmentation of taste organ
      development with increased innervation is complementary to the well-documented
      reduction in taste organ development with sparse innervation. We propose that
      additional taste neurons survived programmed cell death in Bax-deficient mice,
      thereby providing an inductive boost to vallate gustatory development.

PMID- 10931487
TI  - Degranulation, density, and distribution of mast cells in the rat thalamus: a
      light and electron microscopic study in basal conditions and after
      intracerebroventricular administration of nerve growth factor.
AB  - In the adult rat brain mast cells reside selectively in the thalamus. We
      investigated thalamic mast cells stained by acidic toluidine blue or pinacyanol,
      and with histamine immunocytochemistry, focusing on their state of activity
      revealed by degranulation. Mast cells exhibited perivascular prevalence and high
      quantitative variability, between cases and in different sections, with no
      asymmetry or topographical selectivity in thalamic nuclei. Pinacyanol, alone or
      with erythrosine, stained mast cells with higher sensitivity than toluidine blue.
      However, toluidine blue was highly predictive of pinacyanol staining and provided
      the best resolution of mast cell cytoplasmic features. Histamine
      immunocytochemistry labeled 61% of pinacyanol-stained mast cells. Intensely
      toluidine blue-stained granulated cells, as well as cells exhibiting different
      degrees of degranulation that paralleled lighter staining, were observed. The
      response of thalamic mast cells to intracerebroventricular administration of
      nerve growth factor (NGF) and control cytochrome-c injections was evaluated after
      2, 24, and 72 hours. No obvious changes in mast cell number or distribution were
      found after treatment, but massive degranulation was frequently observed after
      NGF administration. Significant decrease of staining intensity of mast cells,
      supporting enhanced degranulation, was documented in NGF-treated animals by
      quantitative image analysis. Ultrastructural features of mast cell degranulation,
      with granule coalescence and matrix dissolution, were detected in untreated and
      NGF-treated cases. The findings point out that mast cells are active in the
      thalamus in basal conditions and that NGF has the potential to elicit long
      lasting degranulation of thalamic mast cells in vivo, exerting a direct effect
      and/or priming these cells to react to endogenous stimuli.

PMID- 10931488
TI  - Spontaneous synaptogenesis in ex vivo sympathetic ganglion and the blockade by
      serum treatment.
AB  - Central denervation for more than 1 month has been shown to cause an increase in
      the number of adrenergic synapses in sympathetic ganglia in vivo. Here, we report
      several lines of evidence that adrenergic synapses may be generated de novo in ex
      vivo superior cervical ganglion (SCG) of adult rats only several hours after the
      isolation. Structures immunoreactive for synaptophysin, a marker of presynaptic
      elements, were drastically decreased 6 days after the preganglionic denervation.
      A significant increase in number of synaptophysin positive boutons was observed
      over 3-8 hours in the denervated SCGs maintained ex vivo at 36 degrees C in
      oxygenated physiologic saline, and this increase was blocked by adding normal
      serum in the saline. Electron microscopic analysis confirmed that the number of
      adrenergic synapses specifically labeled with 5-hydroxydopamine was increased by
      several-fold under the same condition. Intracellular labeling of SCG neurons
      revealed an increase in the incidence (from 8 to 50%) of neurons having dendritic
      plexus after the in vitro incubation. No evidence of axonal sprouting within the
      ganglion was observed. Intracellular recordings from single neurons of denervated
      SCGs revealed that maximum amplitudes of inhibitory postsynaptic potentials,
      which were completely blocked by yohimbine, an alpha2-adrenoceptor antagonist, in
      response to focal stimulation were increased over the several hours. These
      results suggest that dendrites of SCG neurons rapidly develop and exhibit local
      efferent characteristics that underlie the inhibitory synaptic transmission once
      they are subjected to serum deprivation.

PMID- 10931489
TI  - Stereologic study of the hypothalamic infundibular nucleus in young and older
      women.
AB  - Aging in women is associated with dramatic changes in neuronal morphology and
      neuropeptide gene expression in the medial basal hypothalamus. There is
      hypertrophy of neurons expressing substance P and neurokinin B gene transcripts
      in the infundibular (arcuate) nucleus, accompanied by increased tachykinin gene
      expression. In addition, gonadotropin-releasing hormone (GnRH) gene expression is
      increased in a separate subpopulation of neurons within the medial basal
      hypothalamus. In contrast, the number of neurons expressing proopiomelanocortin
      (POMC) mRNA in the infundibular nucleus of older women is decreased. To determine
      whether neuronal degeneration contributes to these phenomena, unbiased
      stereologic methods were used to compare the total number of infundibular neurons
      between groups of young (premenopausal) and older (postmenopausal) women. There
      was no significant difference in the total number of infundibular neurons between
      young (520,000 +/- 42,000 neurons, mean +/- SEM) and older women (505,000 +/-
      51,000 neurons, mean +/- SEM). The mean volume of neuronal somata, however, was
      increased by 40% in the older women (young, 1,860 +/- 180 microm(3) vs. older,
      2,610 +/- 230 microm(3), mean +/- SEM, P < 0.05). These data demonstrate that
      neuronal hypertrophy in older women is not accompanied by degeneration of the
      infundibular nucleus. We conclude that the loss of menstrual cyclicity in middle
      aged women cannot be explained by loss of neurons within the hypothalamic control
      center for reproduction.

PMID- 10931490
TI  - Localization of natriuretic peptides and their activation of particulate
      guanylate cyclase and nitric oxide synthase in the retina.
AB  - In the vertebrate retina, cyclic guanosine monophosphate (cGMP) mediates
      photoreceptor signal transduction and modulates ion channel and gap junction
      conductivity. Although most previous studies have focused on its synthesis by
      nitric oxide (NO)-sensitive soluble guanylate cyclase, cGMP is also synthesized
      by NO-insensitive particulate guanylate cyclases (pGC). Natriuretic peptides and
      their associated pGC-coupled receptors have been reported in retina, but few
      studies have localized these natriuretic peptides or pGCs to specific retinal
      cells or demonstrated that activation of pGCs by natriuretic peptides increases
      cGMP synthesis. In this study, we immunocytochemically localized atrial, brain,
      and C-type natriuretic peptide-like immunoreactivity (ANP-LI, BNP-LI, and CNP-LI,
      respectively) in turtle retina by using isoform specific antisera, and determined
      the ability of each natriuretic peptide isoform to increase cGMP-like
      immunoreactivity (cGMP-LI) in retinal cells. ANP-LI and CNP-LI were localized in
      sparsely distributed amacrine cells with thin, intermittently varicose processes
      in the inner plexiform layer. BNP-LI was localized to abundant somata in the
      inner nuclear and ganglion cell layers and in specific amacrine and horizontal
      cells. Stimulation of turtle eyecups with each of these natriuretic peptides
      increased cGMP-LI in multistratified amacrine cells by means of NO-independent
      mechanisms in the central retina, and in select amacrine and bipolar cells in the
      peripheral retina by a nitric oxide-dependent mechanism. These results indicate
      that natriuretic peptides can modulate the synthesis of cGMP in select retinal
      neurons by two distinct signal transduction pathways in a regionally specific
      manner.

PMID- 10931491
TI  - Neurotransmitters contained in the subcortical extraretinal inputs to the monkey
      lateral geniculate nucleus.
AB  - The lateral geniculate nucleus (LGN) is the thalamic relay of retinal information
      to cortex. An extensive complement of nonretinal inputs to the LGN combine to
      modulate the responsiveness of relay cells to their retinal inputs, and thus
      control the transfer of visual information to cortex. These inputs have been
      studied in the most detail in the cat. The goal of the present study was to
      determine whether the neurotransmitters used by nonretinal afferents to the
      monkey LGN are similar to those identified in the cat. By combining the
      retrograde transport of tracers injected into the monkey LGN with
      immunocytochemical labeling for choline acetyl transferase, brain nitric oxide
      synthase, glutamic acid decarboxylase, tyrosine hydroxylase, or the histochemical
      nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reaction, we
      determined that the organization of neurotransmitter inputs to the monkey LGN is
      strikingly similar to the patterns occurring in the cat. In particular, we found
      that the monkey LGN receives a significant cholinergic/nitrergic projection from
      the pedunculopontine tegmentum, gamma-aminobutyric acid (GABA)ergic projections
      from the thalamic reticular nucleus and pretectum, and a cholinergic projection
      from the parabigeminal nucleus. The major difference between the innervation of
      the LGN in the cat and the monkey is the absence of a noradrenergic projection to
      the monkey LGN. The segregation of the noradrenergic cells and cholinergic cells
      in the monkey brainstem also differs from the intermingled arrangement found in
      the cat brainstem. Our findings suggest that studies of basic mechanisms
      underlying the control of visual information flow through the LGN of the cat may
      relate directly to similar issues in primates, and ultimately, humans.

PMID- 10931492
TI  - Nocturnal tarsier retina has both short and long/medium-wavelength cones in an
      unusual topography.
AB  - The evolutionary position of tarsiers with respect to primates is still debated.
      The type of photoreceptors in the nocturnal Tarsius spectrum retina has been
      compared with the nocturnal New World monkey Aotus trivulgaris and the Old World
      monkey Macaca nemestrina by using immunocytochemical labeling for antisera known
      to be specific for primate cone and rod proteins. In all three species, antisera
      to long/medium (L/M) -wavelength specific cone opsin and cone-specific alpha
      transducin detected a single row of cones. Only Macaca and tarsier retina
      contained cones labeled by antiserum to short (S) -wavelength specific cone
      opsin. Tarsier rod cell bodies were 6-12 deep, depending on retinal eccentricity.
      Tarsier central cones had 2-microm-wide outer (OS) and inner segments, which came
      straight off the cell body. Cone morphology differed little from rods except OS
      were shorter. Macaca cones labeled for 7G6 and calbindin, Aotus cones did not
      label for calbindin, and Tarsius cones did not label for 7G6 or calbindin. In
      tarsier retinal whole-mounts, peak cone density ranged from 11,600-14,200/cones
      mm(2). The 11- to 12-mm-wide peak region centered roughly on the optic disc,
      although foveal counts remain to be completed. Density decreased symmetrically to
      a far peripheral band of 4,200-7, 000/cones mm(2). In contrast, S cone density
      was very low in central retina (0-300/mm(2)), rose symmetrically with
      eccentricity, and peaked at 1,100-1,600/mm(2) in a 2- to 3-mm-wide zone in the
      far periphery. In this zone, S cones were 9-14% of all cones. L/M cones were
      regularly spaced, whereas S cones showed no regular distribution pattern.
      Although the functional characteristics of the tarsier S and L/M cone systems are
      yet to be determined, tarsier cone proteins and distribution have some
      similarities to both New and Old World monkey retinas.

PMID- 10931493
TI  - What is the promise of developmental evolution? Part I: why is developmental
      biology necessary to explain evolutionary innovations?

PMID- 10931494
TI  - Maximal indirect development, set-aside cells, and levels of selection.
AB  - The evolution of metazoan development as described by Davidson et al. (1995.
      Science 270:1319-1325) is readily interpretable in terms of levels-of-selection
      conflicts, for instance, as recently modeled by Michod (1999. Darwinian Dynamics,
      Princeton, NJ: Princeton University Press). Davidson et al. propose certain
      features of early bilaterians including small size, a small and fixed number of
      cell divisions during and subsequent to cleavage, and specification of cell fates
      prior to cell movement. These features suggest constraints on certain parameters
      of Michod's model, specifically t (the time available for cell division) and b
      (the benefit to cells of not cooperating in terms of their rate of replication).
      Such constraints clearly enhance between-cell cooperation and allow
      multicellularity to more easily evolve and be maintained. Nevertheless, these
      constraints are completely abrogated by the phenomenon of "set-aside cells," that
      is, undifferentiated cells that retain indefinite division potential. Levels-of
      selection theory predicts that the evolution of these set-aside cells must be
      accompanied by features which alleviate cell-cell competition, and indeed the
      results of Ransick et al. (1996. Proc Natl Acad Sci USA 93:6759-6763) support
      this prediction: the evolution of "set-aside cells" in metazoans was accompanied
      by the evolution of the sequestration of the germ line.

PMID- 10931495
TI  - Phylogenetic analysis of the Wnt gene family and discovery of an arthropod wnt-10
      orthologue.
AB  - Wnt genes encode a conserved family of secreted signaling proteins that play many
      roles in arthropod and vertebrate development. We have investigated both the
      phylogenetic history and molecular evolution of this gene family. We have
      identified a novel Wnt gene in a diversity of arthropods that it is likely an
      orthologue of the vertebrate Wnt-10 group. Wnt-10 is one of only two cases in
      which orthology between protostome and deuterostome genes could be consistently
      assigned based on our analyses. Despite difficulties in assessing orthologies,
      all of our trees suggest that the most recent common ancestor of protostomes and
      deuterostomes possessed more than the five Wnt genes known from either arthropods
      or nematodes. This suggests that Wnt gene loss has occurred during protostome
      evolution. In addition, we examined the rate of amino acid evolution in the two
      arthropod/deuterostome orthology groups we identified. We found little rate
      variation across taxa, with the exception that Drosophila Wnt-1 is evolving more
      rapidly than all vertebrate and most arthropod orthologues.

PMID- 10931496
TI  - Propagation and maintenance of the 119 human immunoglobulin Vlambda genes and
      pseudogenes during evolution.
AB  - We previously determined a contiguous 1,025,415-nucleotide sequence of the entire
      human immunoglobulin lambda gene locus, in which a total of 36 potentially
      functional Vlambda genes and 33 pseudogenes were localized. We also identified
      many more incomplete Vlambda genes to be characterized further. Some of these
      possessed only a slight sequence homology with the known Vlambda genes, and
      others possessed a high homology but had severely truncated coding regions. Here,
      we made extensive characterization of 50 new Vlambda pseudogenes, totaling 119
      gene segments in the Vlambda gene locus. Of these 119 Vlambda genes, 118 were
      localized within the five Vlambda gene-rich clusters that we previously defined.
      Two of these novel Vlambda pseudogenes possessed the opposite transcriptional
      polarity to all the other Vlambda genes. The present comprehensive analysis of
      119 Vlambda genes validated our previous classification of Vlambda genes and
      provided a basis for a possible mechanism by which a large number of Vlambda
      pseudogenes were propagated and maintained as a particular locus during
      evolution.

PMID- 10931497
TI  - Muscle actin genes and muscle cells in the appendicularian, Oikopleura
      longicauda: phylogenetic relationships among muscle tissues in the urochordates.
AB  - Appendicularians (larvaceans) are planktonic tunicates. They possess a tail
      throughout their life, which marks a distinct difference between appendicularians
      and the other tunicate groups, including salps, doliolids, pyrosomes, and
      ascidians. We isolated cDNA clones encoding muscle-type and cytoplasmic-type
      actin isoforms from the appendicularian, Oikopleura longicauda. The types of the
      actin isoforms were confirmed by amino acid identities in the diagnostic residues
      compared to those of the other chordate muscle and cytoplasmic actins.
      Interestingly the appendicularian muscle actin isoform sequence has an
      intermediate feature between the ascidian tail (larval) muscle actin isoform and
      the body-wall (adult) muscle actin isoform. Analysis of a genomic clone from a
      muscle actin gene revealed that it contains only one intron in the coding region.
      It is located at a position that does not correspond to those of any introns
      reported in other deuterostome actin genes. Whole-mount in situ hybridization
      shows that the muscle actin transcript is detected specifically in the tail
      muscle cells of late tailbud-stage embryos. A signal is also found transiently in
      the region where the heart will form. In adults, the gene is expressed in tail
      muscle cells but not in the heart. Together with results of cytochemical and
      histochemical studies demonstrating the structure of muscle tissue, the present
      study highlights characteristics of appendicularian muscle organization, which
      are compared with those of the larval and adult muscle of ascidians.

PMID- 10931498
TI  - Body weight and tail length divergence in mice selected for rate of development.
AB  - A series of mouse lines has been produced by 19 generations of restricted index
      selection for rate of development during early and late ontogeny. The selection
      program was based on an index with the following four replicated selection
      treatments: E(+) and E(-) were selected to alter birth to 10-day body weight gain
      while holding late gain for both selection lines constant; correspondingly, L(+)
      and L(-) were selected to alter 28- to 56-day body weight gain holding early gain
      for both lines constant. Herein, we characterize response to selection for growth
      rate by analyzing age-specific mouse body weight and tail lengths and for growth
      curves using a logistics model. Selection on developmental rate has resulted in
      divergence in both age-specific and growth curve traits. E(+) and L(+) lines
      reached identical weights during the late selection interval, then diverged to
      unique mature weights. E(-) and L(-) lines similarly achieved identical weights
      during late selection and diverged to unique mature weights. However, the shapes
      of early and late growth curves were significantly divergent, and at least two
      distinct growth patterns are shown to result from selection. Response in body
      weight gain was accompanied by similar, though less pronounced, change in tail
      length traits. Significant response during intervals of restricted growth was
      also found, especially in lines selected for late gain. The evolution of the
      growth trajectory under restricted index selection is discussed in terms of drift
      and available additive genetic variation and covariation.

PMID- 10931499
TI  - Evolutionary history of the uterine serpins.
AB  - A bioinformatics analysis was conducted on the four members of the uterine serpin
      (US) family of serpins. Evolutionary analysis of the protein sequences and 86
      homologous serpins by maximum parsimony and distance methods indicated that the
      uterine serpins proteins form a clade distinct from other serpins. Ancestral
      sequences were reconstructed throughout the evolutionary tree by parsimony. These
      suggested that some branches suffered a high ratio of nonsynonymous to synonymous
      mutations, suggesting episodes of adaptive evolution within the serpin family.
      Analysis of the sequences by neutral evolutionary distance methods suggested that
      the uterine serpins diverged from other serpins prior to the divergence of the
      mammals from other vertebrates. The porcine uterine serpins are paralogs that
      diverged from a single common ancestor within the Sus genus after pigs separated
      from other artiodactyls. The uterine serpins contain several protein kinase C and
      tyrosine kinase phosphorylation sites. These sites may be important for the
      lymphocyte-inhibitory activity of OvUS if, like other basic proteins, OvUS can
      cross the cell membrane of an activated lymphocyte. Internalized OvUS could serve
      as an alternative target to protein kinases important for the mitogenic response
      to antigens.

PMID- 10931500
TI  - Combined-method phylogenetic analysis of Hox and ParaHox genes of the metazoa.
AB  - The clustered Hox genes show a conserved role in patterning the body axis of
      bilaterian metazoans. Increasingly, a broader phylogenetic sampling of non-model
      system organisms is being examined to detect a correlation, if any, between Hox
      gene evolution, and body plan innovations. To assess how Hox gene expression and
      function evolve with changing cluster arrangements, we must be able to reliably
      assign gene orthologies between Hox genes. Recent evidence suggests that a four
      gene proto-Hox cluster duplicated to form the precursor of the present cluster
      and an additional sister-cluster, the ParaHox group. Here, phylogenetic methods
      are used to determine Hox-gene orthologies and to infer probable clustering
      events leading to the current bilaterian Hox complement. This analysis supports
      the ParaHox hypothesis and gives first confirmation that ind (intermediate
      neuroblasts defective) is an anterior ParaHox ortholog from protostomes. This
      analysis supports a proto-Hox cluster of four genes in which the central-class
      member of the ParaHox cluster may have been lost. It is also proposed here that
      ancestral diploblasts had central-class members of both Hox and ParaHox clusters.
      Primitive Hox gene ancestors are estimated by phylogenetic methods and found to
      have no strong affinity to any particular class of extant Hox members.

PMID- 10931501
TI  - Hodin J. 2000. Plasticity and constraints in development and evolution. J exp
      zool (Mol dev evol) 288:1-20
AB  - The sentences on page 8, in paragraph 2 of column 2 reads: In the short-germ
      insects, typified by Drosophila melanogaster, all the segments are specified
      nearly simultaneously in a noncellular, syncitial environment (reviewed in
      Lawrence, '92). By contrast, in the long-germ insects, typified by the
      grasshopper Schistocerca, the segments are specified in a gradual anterior-to
      posterior progression in a cellular environment (reviewed in Patel, '94; Tautz et
      al., '94). The sentences should read: In the long-germ insects, typified by
      Drosophila melanogaster, all the segments are specified nearly simultaneously in
      a noncellular, syncitial environment (reviewed in Lawrence, '92). By contrast, in
      the short-germ insects, typified by the grasshopper Schistocerca, the segments
      are specified in a gradual anterior-to-posterior progression in a cellular
      environment (reviewed in Patel, '94; Tautz et al., '94). The terms "long-germ"
      and "short-germ" were reversed. The germ-type classification is key to the point
      being made in this paragraph: namely, showing that a similar-looking segmental
      plan can be formed by two rather different ontogenetic routes. The author regrets
      the error.

PMID- 10931502
TI  - Exposure to chemicals, offspring sex ratios, and their relevance to teratology.

PMID- 10931503
TI  - Paternal exposures: altered sex ratios.

PMID- 10931504
TI  - Growth retardation and microcephaly induced in mice by placental infection with
      murine cytomegalovirus.
AB  - BACKGROUND: The placenta is regarded as a site of congenital cytomegalovirus
      (CMV) infection. The placental infection of fetuses with murine CMV (MCMV) was
      investigated in a mouse model. METHODS: The placentas and fetuses were examined
      using the polymerase chain reaction (PCR) and Southern blotting for viral DNA and
      immunostaining for viral antigen. Since the transplacental infection rarely
      occurs, the placentas were directly injected with MCMV at day 12.5 of gestation;
      the embryos were then allowed to develop until day 18.5 of gestation. RESULTS:
      Formation of infected foci at day 18. 5 of gestation was found in more than 60%
      of the injected placentas. Infection of about 50% of the embryos occurred from
      the infected placentas. The frequency of infection in the brain was 27%, which
      was the same as that in the liver and higher than that in the lungs. In the
      brains, infected cells were often observed in the ventricular zone of the
      cerebrum and sometimes in the cortical plate and the hippocampus. Developmental
      retardation with microcephaly was observed in about 25% of offspring exposed to
      infection in utero. CONCLUSIONS: These results suggest that formation of infected
      foci in the placenta is important for embryonic congenital infection, and that
      the cerebral ventricular zone is one of the most susceptible sites for CMV
      infection in the embryonic stage.

PMID- 10931505
TI  - Evaluation of the protective activity of deferiprone, an aluminum chelator, on
      aluminum-induced developmental toxicity in mice.
AB  - BACKGROUND: Since deferiprone can be an effective chelating agent for the
      treatment of aluminum (Al) overload, in the present study we investigated whether
      this chelator could protect against Al-induced maternal and developmental
      toxicity in mice. METHODS: A single oral dose of Al nitrate nonahydrate (1,327
      mg/kg) was given on gestation day 12, the most sensitive time for Al-induced
      maternal and developmental toxic effects in mice. At 2, 24, 48, and 72 hr
      thereafter, deferiprone was given by gavage at 0 and 24 mg/kg. Cesarean sections
      were performed on day 18 of gestation and fetuses were examined for malformations
      and variations. RESULTS: Aluminum-induced maternal toxicity was evidenced by
      significant reductions in body weight gain, corrected body weight change, and
      food consumption. Developmental toxicity was evidenced by a significant decrease
      in fetal weight per litter and an increase in the total number of fetuses and
      litters showing bone retardation. No beneficial effects of deferiprone on these
      adverse effects could be observed. By contrast, a more pronounced decrease in
      maternal weight gain and corrected body weight change, as well as a higher number
      of litters with fetuses showing skeletal variations was noted in the group
      exposed to Al nitrate and treated with deferiprone at 24 mg/kg. CONCLUSIONS:
      According to the current results, deferiprone would not be effective to prevent
      Al-induced maternal and embryo/fetal toxicity in mice.

PMID- 10931506
TI  - Transplacental pharmacokinetics and fetal distribution of 2', 3'-didehydro-3'
      deoxythymidine (d4T) and its metabolites in late-term rhesus macaques.
AB  - BACKGROUND: The overall goal of human immunodeficiency virus (HIV) therapy during
      pregnancy is to maintain maternal health and reduce the probability of vertical
      transmission during gestation and delivery, while keeping toxicity risks low.
      Azidothymidine (AZT) is currently recommended for pregnant women infected with
      HIV; however, many pregnant women are unable to tolerate AZT because of toxicity.
      In the present study, the placental transfer and fetal accumulation of the anti
      HIV compound 2',3'-didehydro-3'-deoxythymidine (d4T) and its active
      (triphosphorylated) and inactive (thymine and beta-aminoisobutyric acid)
      metabolites were examined at steady state in late-term rhesus macaques. METHODS:
      On the day of the hysterotomy, the mother was administered an intravenous loading
      dose of d4T, followed by a 3-hr steady-state intravenous infusion that also
      included [(3)H]d4T as a tracer. After 3 hr of infusion, the fetus was delivered
      by cesarean section under halothane/N(2)O anesthesia. Plasma, amniotic fluid, and
      tissues were analyzed for d4T and its inactive metabolites by HPLC; tissue
      samples were analyzed for d4T and active (phosphorylated) metabolites by strong
      anion-exchange HPLC. RESULTS: Maternal steady-state plasma concentrations of d4T
      were 1-2 microg/ml, with a fetal-to-maternal plasma ratio of 0.85 +/- 0.09. The
      fetal tissue distribution of radioactivity was highest in the kidney and lowest
      in the brain. D4T, thymine, and beta-aminoisobutyric acid were detected in all
      fetal tissues examined. CONCLUSIONS: Our data indicate that d4T readily crosses
      the placenta and is present in the fetus as parent compound or its inactive
      metabolites after maternal infusion. Although fetal plasma concentrations of d4T
      were similar to clinical d4T concentrations, no phosphorylated metabolites were
      detected. Teratology 62:93-99, 2000. Published 2000 Wiley-Liss, Inc.

PMID- 10931507
TI  - Antioxidant and GSH-related enzyme response to a single teratogenic exposure to
      the anticonvulsant phenytoin: temporospatial evaluation.
AB  - BACKGROUND: It has been proposed that the anticonvulsant drug phenytoin (PHT)
      requires bioactivation to reactive intermediate(s) to achieve its recognized
      teratogenic potential and that embryonal detoxification power may play a
      fundamental role in the teratogenic response. On this basis, we sought to
      investigate the potential effects of a teratogenic exposure to PHT on the
      activities of antioxidant and GSH-related detoxifying enzymes in gestational
      murine tissues. METHODS: Pregnant Swiss mice were injected intraperitoneally with
      0 (vehicle) or 65 mg/kg of PHT on gestation day (GD) 12 (plug day = GD 1).
      Biochemical determinations, including activities of glutathione transferase,
      glutathione peroxidase, glutathione reductase, glyoxalase I, glyoxalase II,
      catalase, and superoxide dismutase, were carried out on maternal and
      embryonic/fetal livers and in placentas on GD 14 and 19. RESULTS: The major
      findings of this study show that (1) organogenesis-stage conceptal tissues have
      detectable levels of all the tested enzymes; (2) most of the embryonic liver and
      placental enzymes investigated undergo a significant induction within 48 hr (GD
      14) after PHT administration; and (3) in the same tissues a down-regulation of
      enzyme activities is noted near term (GD 19). CONCLUSIONS: Overall, these
      findings show that teratogenic exposure to PHT is associated with a modulation of
      reactive-intermediates-scavenging enzyme activities, and provide further support
      for role of generation of reactive intermediates in PHT-induced teratogenesis.

PMID- 10931508
TI  - Assessment of developmental toxicity of antiretroviral drugs using a rat whole
      embryo culture system.
AB  - BACKGROUND: Previous guidelines for HIV-infected pregnant women have recommended
      zidovudine (ZDV) monotherapy during the second and third trimesters of pregnancy
      to prevent fetal HIV infection. New guidelines suggest that women should continue
      or be offered combination antiretroviral therapy (including protease inhibitors)
      during pregnancy. Nevertheless, little animal or human toxicity data underlie
      these recommendations. METHODS: We used an in vitro rat whole embryo culture
      system to assess the embryo toxicity of various nucleoside analogues, namely,
      ZDV, dideoxyinosine (ddI), and 2', 3'-dideoxycytidine (ddC), and the HIV-1
      protease inhibitor, indinavir, both alone and in combination. RESULTS: Although
      human fetal concentrations of these compounds are unknown, no gross abnormalities
      were detected after incubation with these agents, either alone or in combination
      at concentrations that would be expected to be achievable in human maternal serum
      (1-50 microM). ZDV in combination with ddC at >100 microM, resulted in severe
      growth retardation and morphologic abnormalities not seen with either agent
      singly. CONCLUSIONS: We conclude that the combination of ZDV/ddC results in
      severe concentration-dependent embryo toxicity. No growth retardation or gross
      morphologic abnormalities were found for any of the agents, either singly or in
      combination, at clinically relevant concentrations.

PMID- 10931509
TI  - Teratogenic effects of bis-diamine on early embryonic rat heart: an in vitro
      study.
AB  - BACKGROUND: Bis-diamine induces cardiac defects, including conotruncal anomalies
      in rat embryos when the agent is administered to the mother. To evaluate the
      teratogenic effects and mechanism of bis-diamine, we performed morphological and
      immunohistochemical analyses of early rat embryos cultured in medium containing
      bis-diamine. METHODS: The embryos were removed from mother rats on gestational
      day 10.5 and cultured in medium containing 1 mg of bis-diamine for 6 hr. The
      embryos were then cultured in medium only for another 6, 12, 18, and 42 hr,
      corresponding to embryonic day (ED) 11.0, 11.25, 11.5, and 12.5, respectively.
      Some embryos from the same mothers were used as controls and were cultured in
      medium only for the corresponding periods to the embryos exposed to bis-diamine.
      Some mother rats were given a single oral dose of 200 mg of bis-diamine on
      gestational day 10.5. Embryos from these pregnant rats were removed 6 hr after
      the oral administration of bis-diamine, and were also cultured in medium only for
      6, 12, 18, and 42 hr. RESULTS: No cardiac abnormalities were detected in the
      controls at any stage of development. Thirty-three of 51 (65%) embryos exposed to
      bis-diamine and 15 of 20 (75%) embryos removed from bis-diamine-administered
      mothers showed abnormal cardiac development, including dilated ventricle,
      elongation of outflow tract, and pericardial defect on ED 11.5. Four of six (67%)
      embryos exposed to bis-diamine, and five of seven (71%) removed from bis-diamine
      administered mothers also presented almost the same cardiac abnormalities on ED
      12.5. No cardiac abnormalities were detected in bis-diamine-treated embryos
      before ED 11.5. In addition, the expression of neural cell adhesion molecule (N
      CAM) was examined using immunohistochemical methods. Fewer N-CAM immunoreactive
      cells were detected in the third and fourth aortic arches in the bis-diamine
      treated embryos than in controls on ED 11.5. However, more N-CAM immunoreactive
      cells were detected in the bis-diamine-treated embryos than in controls on ED
      12.5. CONCLUSIONS: These results suggest that bis-diamine induces cardiac
      anomalies by delaying the migration of neural crest cells into the heart and by
      disturbing the proliferation of pericardial precursor during early cardiac
      development.

PMID- 10931510
TI  - Retinoic acid, midkine, and defects of secondary neurulation.
AB  - BACKGROUND: Retinoic acid (RA) is necessary for normal differentiation of the
      tail bud into the secondary neural tube. Excess RA, however, is teratogenic and
      causes neural tube defects (NTDs). The way in which RA modulates secondary
      neurulation is unclear but probably involves RA-regulated downstream genes such
      midkine (MK), which encodes a growth factor implicated in tail bud mesenchymal
      neuroepithelial conversion. Our objective was to determine whether RA-deficiency
      would produce similar defects and if MK is involved. METHODS: Citral, a drug that
      blocks endogenous RA formation, as well as a neutralizing antibody, were used to
      block RA activity in chick embryos. Immunohistochemistry and in situ
      hybridization were used to localize RA and MK in the tail bud. Competitive RT-PCR
      was used to examine the effects of excess RA and RA deficiency due to citral on
      the expression of MK mRNA. RESULTS: Citral-induced NTDs displayed a morphological
      resemblance to those caused by excess RA. However, citral treatment did not
      significantly increase embryonic mortality, and RA rescue of citral-treated
      embryos proved unsuccessful. MK mRNA was detected in the differentiating tail bud
      by in situ hybridization. Competitive RT-PCR showed that excess RA decreased MK
      expression by 60%. Doses of citral that caused a comparable incidence of defects,
      however, caused only a 25% decrease. CONCLUSIONS: The results show that excess RA
      and RA deficiency both cause defects of secondary neurulation. While excess RA
      decreased MK expression, RA deficiency had minimal effects. However, whether or
      not MK is an intermediary in the developmental phenomena regulated
      physiologically or pathologically by RA remains to be elucidated.

PMID- 10931511
TI  - Teratology society: presentation to the FDA public meeting on safety issues
      associated with the use of dietary supplements during pregnancy.

PMID- 10931512
TI  - Evaluation of a combination drug with multiple doses in unbalanced factorial
      design clinical trials.
AB  - Flexibilities for sample size allocation are often demanded for achieving
      multiple study objectives in combination drug trials. The global tests of Hung,
      Chi and Lipicky are extended for analysis of unbalanced factorial design trials
      to test the hypothesis that at least one of the non-zero dose combinations of two
      drugs is more effective than the respective component doses. When the dose
      combinations have heterogeneous effect sizes, an unbalanced design may induce
      greater power than the balanced design. An adjusted p-value approach is proposed
      for testing the individual dose combinations under the condition that the maximum
      type I error probability is protected.

PMID- 10931513
TI  - An approximate unconditional test of non-inferiority between two proportions.
AB  - This paper investigates an approximate unconditional test for non-inferiority
      between two independent binomial proportions. The P-value of the approximate
      unconditional test is evaluated using the maximum likelihood estimate of the
      nuisance parameter. In this paper, we clarify some differences in defining the
      rejection regions between the approximate unconditional and conventional
      conditional or unconditional exact test. We compare the approximate unconditional
      test with the asymptotic test and unconditional exact test by Chan (Statistics in
      Medicine, 17, 1403-1413, 1998) with respect to the type I error and power. In
      general, the type I errors and powers are in the decreasing order of the
      asymptotic, approximate unconditional and unconditional exact tests. In many
      cases, the type I errors are above the nominal level from the asymptotic test,
      and are below the nominal level from the unconditional exact test. In summary,
      when the non-inferiority test is formulated in terms of the difference between
      two proportions, the approximate unconditional test is the most desirable,
      because it is easier to implement and generally more powerful than the
      unconditional exact test and its size rarely exceeds the nominal size. However,
      when a test between two proportions is formulated in terms of the ratio of two
      proportions, such as a test of efficacy, more caution should be made in selecting
      a test procedure. The performance of the tests depends on the sample size and the
      range of plausible values of the nuisance parameter. Published in 2000 by John
      Wiley & Sons, Ltd.

PMID- 10931514
TI  - Estimating disease prevalence from two-phase surveys with non-response at the
      second phase.
AB  - In this paper we compare several methods for estimating population disease
      prevalence from data collected by two-phase sampling when there is non-response
      at the second phase. The traditional weighting type estimator requires the
      missing completely at random assumption and may yield biased estimates if the
      assumption does not hold. We review two approaches and propose one new approach
      to adjust for non-response assuming that the non-response depends on a set of
      covariates collected at the first phase: an adjusted weighting type estimator
      using estimated response probability from a response model; a modelling type
      estimator using predicted disease probability from a disease model; and a
      regression type estimator combining the adjusted weighting type estimator and the
      modelling type estimator. These estimators are illustrated using data from an
      Alzheimer's disease study in two populations.

PMID- 10931515
TI  - Measuring the effectiveness of diagnostic markers in the presence of measurement
      error through the use of ROC curves.
AB  - The area under the receiver operating characteristic curve is frequently used to
      assess the effectiveness of diagnostic markers in distinguishing between diseased
      and healthy individuals. These markers are generally subject to measurement
      error. In this paper confidence intervals for the area under the curve are
      developed which take measurement error into account. These intervals depend on
      the availability of replicated observations for the subject. Both equal and
      unequal numbers of replicates per subject are considered. The practice of
      averaging over replicates and then ignoring measurement error is examined and
      found wanting.

PMID- 10931516
TI  - Estimating the value of an internal biostatistical consulting service.
AB  - Biostatistical consulting is a service business. Although a consulting
      biostatistician's goal is long-term collaborative relationships with
      investigators, this is the same as the long-term goal of any business: having a
      group of contented, satisfied customers. In this era of constrained resources, we
      must be able to demonstrate that the benefit a biostatistical consulting group
      provides to its organization exceeds its actual cost to the institution. In this
      paper, I provide both a theoretical framework for assessing the value of a
      biostatistical service and provide an ad hoc method to value the contribution of
      a biostatistical service to a grant. Using the methods described, our
      biostatistics group returns more than $6 for each dollar spent on institutional
      support in 1998.

PMID- 10931517
TI  - Familial tendency to foetal loss analysed with Bayesian graphical models by Gibbs
      sampling.
AB  - This paper presents several models for investigating whether the HLA
      allogenotypes DR1/Br, DR3 and DR10 are genetic markers for a predisposition of
      experiencing unexplained recurrent foetal losses. A total of 199 women from 113
      families answered questionnaires concerning their pregnancies and 145 of these
      women were HLA typed. The analysis of the data is complicated as dependencies
      between pregnancy outcomes are expected. The main purpose of the paper is to
      illustrate how such analyses can be performed using Bayesian graphical models and
      Gibbs sampling. The analyses are made using the programs BUGS and CODA. Markov
      chain Monte Carlo analyses within a Bayesian framework have become easier with
      the introduction of these programs. However, experience shows that some caution
      is required so we recommend making some initial analyses using very simple models
      and perhaps approximative methods, followed by a model development introducing
      increasing complexity.

PMID- 10931518
TI  - Comparing time to onset of response in antidepressant clinical trials using the
      cure model and the Cramer-von Mises test.
AB  - Currently available antidepressants have a delayed onset of action and there is
      considerable interest in developing new products which exhibit a shorter time to
      response. Previous authors have suggested using a cure model to characterize the
      time to response for the combination of the patients who respond and the patients
      who do not respond. In this paper, we use the cure model and propose a Cramer-von
      Mises statistic to compare the time to response distributions for patients who
      respond to therapy. The asymptotic null distribution of the statistic is derived.
      A bootstap procedure is also proposed for sample sizes typical in antidepressant
      clinical trials. Results of the simulation study suggest that for common designs
      and sample sizes used in such trials, the statistic has reasonable size and power
      properties as long as censoring is moderate.

PMID- 10931519
TI  - The use of sliding time windows for the exploratory analysis of temporal effects
      of smoking histories on lung cancer risk.
AB  - To examine the time-dependent effects of exposure histories on disease we use
      sliding time windows as an exploratory alternative to the analysis of variables
      like time since last exposure and duration of exposure. The method fits a series
      of risk models which contain total cumulative exposure and an additional
      covariate for exposures received during fixed time intervals. Characteristics of
      the fitted models provide insight into the influence of exposure increments at
      different times on disease risk. A simulation study is performed to check the
      validity of the approach. We apply the method to data from a recent German case
      control study on smoking and lung cancer risk with about 4300 lung cancer cases
      and a similiar number of controls. The sliding time window approach indicates
      that the amount of cigarettes smoked from two to 11 years before disease
      incidence is most predicitive of lung cancer incidence. Among different smoking
      profiles that result in the same lifelong cumulative number of cigarettes smoked,
      those with a concentration of smoked cigarettes within 20 years before interview
      bear substantially larger risk than others.

PMID- 10931520
TI  - The probability of a cancer cluster due to chance alone.
AB  - We propose to use a very simple model to test whether a cancer cluster is due to
      chance alone. We focus on the acute childhood leukaemia cluster in Columbus,
      Ohio. In 1975, 12 leukaemia cases were observed in Columbus while the expected
      number is 6 cases per year. According to our simple model, the probability of
      such an occurrence, due to chance alone, is less than 1 per cent. However, if we
      divide the child population of the U.S.A. into 200 regions (each region having
      200 000 children) then the probability that at least one region will see, in a
      given year, 12 or more cases is higher than 80 per cent. So in this sense the
      Columbus cluster could be attributed to chance alone. However, the probability
      that any of the 200 regions see 18 cases or more in a given year is almost 0.
      Thus, a cluster of 18 or more cases in a region of 200 000 children should be
      regarded as highly suspicious and should be investigated.

PMID- 10931521
TI  - Radial glia phenotype: origin, regulation, and transdifferentiation.
AB  - Radial glial cells play a major guidance role for migrating neurons during
      central nervous system (CNS) histogenesis but also play many other crucial roles
      in early brain development. Being among the earliest cells to differentiate in
      the early CNS, they provide support for neuronal migration during embryonic brain
      development; provide instructive and neurotrophic signals required for the
      survival, proliferation, and differentiation of neurons; and may be
      multipotential progenitor cells that give rise to various cell types, including
      neurons. Radial glial cells constitute a major cell type of the developing brain
      in numerous nonmammalian and mammalian vertebrates, increasing in complexity in
      parallel with the organization of the nervous tissue they help to build. In
      mammalian species, these cells transdifferentiate into astrocytes when neuronal
      migration is completed, whereas, in nonmammalian species, they persist into
      adulthood as a radial component of astroglia. Thus, our perception of radial glia
      may have to change from that of path-defining cells to that of specialized
      precursor cells transiently fulfilling a guidance role during brain histogenesis.
      In that respect, their apparent change of phenotype from radial fiber to
      astrocyte probably constitutes one of the most common transdifferentiation events
      in mammalian development.

PMID- 10931522
TI  - Adult rat and human bone marrow stromal cells differentiate into neurons.
AB  - Bone marrow stromal cells exhibit multiple traits of a stem cell population. They
      can be greatly expanded in vitro and induced to differentiate into multiple
      mesenchymal cell types. However, differentiation to non-mesenchymal fates has not
      been demonstrated. Here, adult rat stromal cells were expanded as
      undifferentiated cells in culture for more than 20 passages, indicating their
      proliferative capacity. A simple treatment protocol induced the stromal cells to
      exhibit a neuronal phenotype, expressing neuron-specific enolase, NeuN,
      neurofilament-M, and tau. With an optimal differentiation protocol, almost 80% of
      the cells expressed NSE and NF-M. The refractile cell bodies extended long
      processes terminating in typical growth cones and filopodia. The differentiating
      cells expressed nestin, characteristic of neuronal precursor stem cells, at 5 hr,
      but the trait was undetectable at 6 days. In contrast, expression of trkA, the
      nerve growth factor receptor, persisted from 5 hr through 6 days. Clonal cell
      lines, established from single cells, proliferated, yielding both
      undifferentiated and neuronal cells. Human marrow stromal cells subjected to this
      protocol also differentiated into neurons. Consequently, adult marrow stromal
      cells can be induced to overcome their mesenchymal commitment and may constitute
      an abundant and accessible cellular reservoir for the treatment of a variety of
      neurologic diseases.

PMID- 10931523
TI  - Differential expression of delta opioid receptors and mRNA in proliferating
      astrocytes during the cell cycle.
AB  - Previous immunohistochemical and radioligand binding studies have shown a cell
      cycle-dependent regulation of the delta opioid receptor (DOR). The relationship
      between DOR expression and mitosis in primary astroglial cultures of rat cerebral
      cortex was investigated in this study. The cultures were arrested during the
      G(1)/S transition or during mitosis. The DOR protein level increased twofold (P =
      0.009) during mitosis and DOR mRNA level increased threefold (P = 0.002) during
      the G(1)/S transition compared to nonsynchronized cultures. DOR mRNA was also
      elevated (1.6-fold, P = 0.008) during the G(1)/S transition compared with mitotic
      cells. A premitotic increase in DOR mRNA suggests that elevated DOR protein
      levels during mitosis might be regulated during transcription.

PMID- 10931524
TI  - Gtx, an oligodendrocyte-specific homeodomain protein, has repressor activity.
AB  - Myelin, a multilamellar membrane structure that facilitates nerve conduction, is
      synthesized in the central nervous system (CNS) by oligodendrocytes. Gtx, a
      member of the homeodomain family of transcriptional factors, is a candidate
      regulator of myelin gene expression, because it is uniquely expressed in
      myelinating oligodendrocytes in postnatal rodent brain. To analyze the regulatory
      activity of Gtx, we first identified the optimal Gtx-binding sequence using an in
      vitro DNA-binding assay. This sequence, (A/T)TTAATGA, contains a TAAT core and is
      similar, but not identical, to that of other homeodomain protein binding sites.
      When coexpressed in cultured cells along with a minimal promoter containing five
      tandem repeats of this optimal Gtx-binding sequence, Gtx demonstrated repressor
      activity, which was also present when Gtx was tethered to DNA by way of the
      strong GAL4 DNA-binding domain. Truncations of the GAL4-Gtx fusion identified a
      portable repressor domain within a relatively proline/alanine-rich region N
      terminal to the Gtx homeodomain. Cotransfection of a Gtx expression vector into a
      variety of cell lines, including oligodendrocytes, along with constructs
      containing portions of the PLP, MBP, or Gtx promoters fused to a reporter gene,
      however, did not modulate transcription from any of these promoter constructs.
      These data support the notion that the oligodendrocyte-specific homeodomain
      protein Gtx can act as a transcriptional repressor. In addition, they suggest
      that interaction of Gtx with other, as yet undefined, transcriptional regulators
      modifies Gtx activity in oligodendrocytes.

PMID- 10931525
TI  - Alternative splicing prevents transferrin secretion during differentiation of a
      human oligodendrocyte cell line.
AB  - Transferrin, the iron-transport protein of vertebrate serum, is synthesized
      mainly in the liver, from which it is secreted into the blood. Transferrin is
      also synthesized in oligodendrocytes and is an early marker of their
      differentiation. We have analyzed the regulation of transferrin expression in HOG
      cells, a human oligodendrocyte cell line. Transferrin expression was correlated
      with the appearance of oligodendrocyte differentiation markers when cells were
      exposed to differentiation medium. In contrast to the protein expressed in
      hepatocytes or in Sertoli cells, transferrin was secreted by neither HOG cells
      nor immature rat primary oligodendrocytes in vitro. Moreover, transferrin appears
      to be localized in the cytosol and not in the secretory compartment, as is
      expected for secreted proteins. This transferrin localization was correlated with
      the synthesis of a specific transcript, resulting from an alternative splicing,
      which leads to the elimination of the signal peptide sequence. These results
      suggest the existence of a functional difference between transferrin synthesized
      in the brain and in other organs such as liver and testis. They are in accordance
      with the hypothesis that transferrin plays a specific role, other than iron
      transport, in oligodendrocyte maturation and in the myelination process.

PMID- 10931526
TI  - Regulation of tissue inhibitor of metalloproteinase-3 (Timp-3) mRNA expression
      during rat CNS development.
AB  - To preserve tissue integrity during the structural rearrangements that occur
      during central nervous system (CNS) development, an intricate balance between
      extracellular matrix (ECM) synthesis and degradation must be maintained. The
      matrix metalloproteinases (MMPs) are believed to be the main mediators of ECM
      degradation. Because MMPs function in the turnover of a broad-spectrum of ECM
      proteins their activity is tightly regulated by interaction with tissue
      inhibitors of metalloproteinases (TIMPs). Whereas the primary function of TIMPs
      is to inhibit MMP activity, evidence is mounting that TIMPs are multifunctional
      molecules that exert diverse cell biological functions distinct from their MMP
      inhibitory activities. Although the role of MMPs and TIMPs in the morphogenesis
      of non-neural tissues has been investigated, to date few studies have analyzed
      MMP or TIMP expression during CNS development. In the present report, we
      demonstrate the regulation of Timp-3 mRNA expression throughout the course of CNS
      development. In particular, Timp-3 mRNA is expressed in embryonic ventricular
      zones and the postnatal subventricular zone (SVZ). In addition, Timp-3 is
      expressed in the rostral migratory steam (RMS) to the olfactory bulb in a pattern
      similar to the ECM proteoglycan brevican. These data suggest that TIMP-3 and
      brevican may act in concert to guide neuronal migration along the RMS.

PMID- 10931527
TI  - Requirement of glycolytic and mitochondrial energy supply for loading of Ca(2+)
      stores and InsP(3)-mediated Ca(2+) signaling in rat hippocampus astrocytes.
AB  - A major consequence of brain hypoxia and hypoglycemia, which induces the
      detrimental effects of stroke, is impaired ATP supply. However, it is not yet
      clear to which degree reduced cellular ATP production affects Ca(2+) homeostasis
      and Ca(2+) signaling of glia cells. Here we studied in cultured hippocampal
      astrocytes the influence of inhibition of cellular energy supply on Ca(2+) load
      of intracellular stores. Inhibition of glycolysis in the presence of substrates
      for mitochondrial respiration resulted in an average drop of intracellular ATP
      levels by 35%. Inhibition of oxidative phosphorylation reduced intracellular ATP
      on average by 16%. With inhibition of both glycolysis and mitochondrial ATP
      production, intracellular ATP level was drastically reduced (84%). In astrocytes
      in Ca(2+)-free buffer, cytosolic [Ca(2+)](i) was dramatically increased due to
      inhibition of glycolysis, even in the presence of mitochondrial substrates.
      However, only a minor increase of [Ca(2+)](i) was observed with inhibitors of
      mitochondrial ATP synthesis. Remarkably, the moderate reduction of ATP levels
      found with inhibitors of glycolysis caused a severe loss of Ca(2+) from
      cyclopiazonic acid (CPA)-sensitive Ca(2+) stores. Consequently, inhibition of
      glycolysis reduced P2Y receptor- or thrombin receptor-evoked Ca(2+) responses on
      average by 95%, whereas a reduction of only 26% was found with mitochondrial
      inhibitors. In conclusion, glycolysis is the most important source of ATP for the
      maintenance of Ca(2+) load in stores that are required for transmitter-induced
      signaling. These results are consistent with the concept that a local ATP source
      in the vicinity of endoplasmic reticulum Ca(2+) pumps is required.

PMID- 10931528
TI  - Proliferative and migratory responses of astrocytes to in vitro injury.
AB  - An in vitro "scratch-wound" model was used to evoke and investigate some
      astroglial responses to mechanical injury. The changes in the morphology,
      locomotion, and proliferation of injured astrocytes were analysed under culture
      conditions devoid of blood-derived cells responsible for activating the
      inflammatory cascade. The rate of proliferation was determined by
      immunocytochemical detection of BrdU-incorporating cells located next to or far
      from the wound. The motility of individual cells and the mass-advancement of cell
      assemblies were monitored by computer controlled video-microscopy both in injured
      monolayers and in preparations of single cells or aggregates of astrocytes. The
      large sets of digitalized data allowed a reliable statistical evaluation of
      changes in cell positions providing a quantitative approach for studies on
      dynamics of cell locomotion. The results indicated that cultivated astrocytes
      respond to injury (1) with enhanced nestin immunoreactivity at the expanding
      processes, (2) with increased mitotic activity exceeding the rate caused by the
      liberation from contact inhibition, but (3) without specific, injury-induced
      activation of cell locomotion. Some advantages and drawbacks of "scratch-wound"
      models of astrocytic responses to mechanical injury are presented and discussed.

PMID- 10931529
TI  - Galectin-3 is upregulated in microglial cells in response to ischemic brain
      lesions, but not to facial nerve axotomy.
AB  - We have recently demonstrated that the beta-galactoside-specific lectin galectin
      3 is expressed by microglial cells in vitro, but not by normal resting microglia
      in vivo. In the present study, we have analyzed the expression of galectin-3 by
      microglia under traumatic conditions in vivo using two experimental rat models
      which substantially differ in the severity of lesion related to a breakdown of
      the blood-brain barrier (BBB) and the occurrence of inflammatory processes. These
      two features are absent after peripheral nerve lesion and present after cerebral
      ischemia. Here we show that, following facial nerve axotomy under conditions
      allowing (nerve anastomosis) or not subsequent regeneration (nerve resection),
      galectin-3 is not expressed by microglia in the corresponding facial nucleus 1
      112 days after lesion. Galectin-3 is also absent in microglia at sites of a
      defective BBB in the normal brain, such as the circumventricular organs.
      Following experimental ischemia (i.e., permanent occlusion of the middle cerebral
      artery), in contrast, galectin-3 becomes strongly expressed by activated
      microglia as early as 48 hours after trauma, as determined by
      immunohistochemistry and Western blot analysis. Our findings suggest that the
      expression of galectin-3 by microglia in vivo correlates with the state of
      microglial activation.

PMID- 10931530
TI  - Proteasome inhibition results in increased poly-ADP-ribosylation: implications
      for neuron death.
AB  - This study demonstrates the ability of proteasome inhibitors (lactacystin, MG
      115, MG 132) adenosine diphosphate to induce a time- and dose-dependent increase
      in poly-ADP-ribosylation (PAR) in the neural PC6 cell line, a subclone of PC12
      cells. Elevated levels of PAR contribute to the toxicity associated with impaired
      proteasome activity, based on the ability of PAR inhibitors to ameliorate the
      toxicity associated with the application of lactacystin, MG 115, and MG 132.
      Proteasome inhibitors induced the accumulation of PAR and neuron death in primary
      hippocampal neuron cultures, which were both ameliorated by treatment with PAR
      inhibitors. Together, these data indicate a role for increased PAR in the
      toxicity associated with proteasome inhibition, and suggest that inhibitors of
      PAR may provide neuroprotection in conditions where proteasome inhibition occurs.

PMID- 10931531
TI  - Neuroprotective effect of cyclic GMP against radical-induced toxicity in cultured
      spinal motor neurons.
AB  - We have previously reported that nitric oxide-related cyclic guanosine-3',5'
      monophosphate (GMP) protected spinal nonmotor neurons, but not motor neurons
      against chronic glutamate-induced toxicity, which is associated with selective
      motor neuronal death after glutamate stress. In this report, we investigated the
      effect of cyclic GMP against reactive oxygen species (ROS)-induced toxicity in
      cultured neurons from embryonic rat spinal cords. Pretreatment with a cGMP
      analogue, 8-bromoguanosine monophosphate (8br-cGMP), for 12-24 hours protected
      both spinal motor neurons and nonmotor neurons against injury induced by either
      hydrogen peroxide (H(2)O(2)), or a glutathione depletor, L-buthionine-[S,R]
      sulfoximine (BSO). This protective effect was reversed by coadministration with
      the cGMP-dependent protein kinase (PKG) inhibitor Arg-Lys-Arg-Ala-Arg-Lys-Glu.
      Interestingly, when cultures were exposed to BSO for 24 hours to allow
      irreversible inhibition of glutathione synthesis, 8br-cGMP protected only
      nonmotor neurons. Our results indicate that cGMP attenuates oxidative injury to
      cultured spinal neurons, in a mechanism associated with glutathione synthesis.

PMID- 10931532
TI  - A beta peptides and calcium influence secretion of the amyloid protein precursor
      from chick sympathetic neurons in culture.
AB  - The major constituent of amyloid plaques in the Alzheimer disease (AD) brain is
      the amyloid protein (A beta). A beta has been shown to be neurotoxic to cells,
      but the exact mechanism of its effects are still not known. Most studies have
      focussed on A beta neurotoxicity, but little is known about the effect of A beta
      peptides on cellular protein metabolism and secretion. To examine the effect of A
      beta peptides on APP secretion, chick sympathetic neurons were metabolically
      labeled with [(35)S]methionine and the amounts of radiolabeled APP and A beta
      quantitated. Several A beta peptides (A beta(25-35), [pyroglu(3)]A beta(3-40),
      and [pyroglu(11)]A beta(11-40)) inhibited secretion of [(35)S]APP and increased
      cell-associated [(35)S]APP. There was also a 2-2.5-fold increase in secretion of
      several other proteins when cells were incubated with A beta(25-35). However, the
      amount of A beta secreted into the medium was decreased. Treatment of cells with
      the calcium ionophore A23187 caused a 1.5-fold increase in secreted [(35)S]APP
      and a decrease in cell-associated [(35)S]APP. Although L-type voltage-dependent
      calcium channels (VDCC) have been implicated in A beta toxicity, the effect of L
      type VDCC on APP secretion has not previously been examined. The L-type VDCC
      antagonists nifedipine and diltiazem both increased [(35)S]APP secretion into the
      medium but did not influence the effect of A beta on [(35)S]APP secretion. These
      studies suggest that A beta interferes with the secretory pathway of APP. Insofar
      as secreted APP has been proposed to have a neuroprotective function, the
      accumulation of A beta in the AD brain could decrease secreted APP and thereby
      indirectly increase A beta toxicity.

PMID- 10931533
TI  - Effects of typical and atypical antipsychotics on neuropeptide Y in rat brain
      tissue and microdialysates from ventral striatum.
AB  - The main goal of this study was to investigate effects of typical (haloperidol)
      and atypical (risperidone) antipsychotic drugs on brain regional neuropeptide Y
      (NPY)-like immunoreactivity (-LI) tissue concentrations and on release of NPY-LI
      in freely moving rats. An additional aim was to explore the effect of d
      amphetamine on NPY-LI release following pretreatment with typical and atypical
      antipsychotics. During a 4-week period, male Wistar rats were fed chow to which
      vehicle, risperidone (1.15 mg/100 g food or 2.3 mg/100 g food), or haloperidol
      (1.15 mg/100 g food) were added. In one series of experiments, the animals were
      sacrificed on day 30 with focused microwave irradiation, the brain regions
      dissected and extracted for radioimmunoassay of NPY-LI. In another experimental
      series, probes were inserted into the ventral striatum. The perfusates were
      collected at 60-min intervals; NPY-LI was determined by radioimmunoassay.
      Haloperidol significantly increased NPY-LI in hypothalamus and the occipital
      cortex. In contrast, haloperidol decreased tissue levels of NPY-LI in striatum.
      Moreover, haloperidol and risperidone also significantly decreased extracellular
      NPY-LI concentrations in the ventral striatum. d-amphetamine (1.5 mg/kg)
      significantly increased extracellular NPY-LI in the vehicle group. Both
      haloperidol and risperidone pretreatments abolished the effect of d-amphetamine.
      The results show that d-amphetamine as well as haloperidol and risperidone
      selectively and specifically affect NPY-LI concentrations in brain tissue and
      microdialysates and that the effect of d-amphetamine is abolished by both typical
      and atypical antipsychotics.

PMID- 10931535
TI  - Imidazolium molecular motifs located on dicationic frameworks. Electrospray mass
      spectrometric observation of carbenes: imidazolylidenes
AB  - Electrospray ionization mass spectral analysis of simple dicationic imidazolium
      prototypes (M.2X) is reported and direct observation was obtained for proton
      mediated ion-molecule reactions in the gas phase. The comparative ESI-MS study
      with heterophanes 1a.2Cl and 3.2Br, the open chain system 5.2Br, and their
      regiospecific deuterated counterparts 2a.2Cl, 4.2Br and 6.2Br showed that the
      nature of the frameworks containing two imidazolium subunits modulates their
      electrospray ionization, changing the stability of the common characteristic
      peaks: the carbene specie [M - H](+) or [M - D](+) as well as [M](2+) and [M.
      X](+).Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931534
TI  - Induction of apoptosis in glioma cell lines by TRAIL/Apo-2l.
AB  - TRAIL/Apo-2L, a novel cytokine, is a member of the tumor necrosis factor (TNF)
      family and serves as an extracellular signal triggering apoptosis. TRAIL/Apo-2L
      is capable of killing various transformed cells but not unstimulated primary T
      cells. In this study, five human glioma cells (U87, U118, U178, U563, and A172)
      were examined for their susceptibility to the apoptotic effects of TRAIL/Apo-2L.
      TRAIL/Apo-2L cDNA was isolated by RT-PCR, and recombinant TRAIL/Apo-2L protein
      was purified by the pMAL-c2 system (New England Biolabs, Beverly, MA). Exposure
      of A172 cells to bacterially expressed soluble TRAIL/Apo-2L fusion protein at a
      concentration of 1 microg/ml resulted in significant cell death over a 24-h
      period. Three experiments were performed to suggest that the TRAIL/Apo-2L killing
      was through the induction of apoptosis of A172 target cells. In addition, the
      expression of TRAIL/Apo-2L in different glioma cells was found to be variable,
      and TRAIL/Apo-2L-induced apoptosis was in a cell type-dependent manner. Some
      correlation between the susceptibility to TRAIL/Apo-2L and the expression level
      of one of its cognate receptors, DR4, was observed. In addition, cycloheximide
      worked synergistically with TRAIL/Apo-2L to induce apoptosis in glioma cells.

PMID- 10931536
TI  - Capillary electrochromatography/nanoelectrospray mass spectrometry for attomole
      characterization of peptides.
AB  - The successful coupling of capillary electrochromatography (CEC) to an ion trap
      mass spectrometer via a nanoelectrospray interface (nESI) is described. Using a
      conductively coated tip butted to the end of a CEC column, it was possible to
      obtain a stable spray without any sheath liquid being employed. Selected small
      peptides were separated with CEC columns (100 microm i.d./25 cm long) packed with
      3 microm Hypersil C8 or C18 bonded silica particles with an eluent composed of
      ammonium acetate/acetonitrile. Peptide mixtures of desmopressin, peptide A,
      oxytocin, carbetocin and [Met(5)]-enkephalin were detected in the mid-attomole
      range, which is the lowest amount analyzed using CEC combined with MS detection.
      It was also observed that sensitivity can be compromised at higher separation
      voltages. We demonstrate that CEC/nESI-MS, at the current stage of development,
      represents one of the most sensitive systems for peptide analysis.

PMID- 10931537
TI  - Electron ionization study of ammonia micro-clusters
AB  - An electron impact ion source on a double focusing sector field mass spectrometer
      was used to investigate ammonia micro-clusters produced by the adiabatic free jet
      expansion of ammonia gas. The appearance energies for [NH(3)](n)(+), n </= 9,
      ions have been determined. Results of measurements of appearance pressures of
      selected clusters are described for a range of operating conditions. An empirical
      formula describing the ammonia clusters production is proposed. Copyright 2000
      John Wiley & Sons, Ltd.

PMID- 10931538
TI  - Analysis of N-acetylated hexosamine monosaccharides by ferrocenyl boronation and
      tandem electrospray ionization mass spectrometry.
AB  - A tandem electrospray mass spectrometric (MS(n)) technique for the analysis of N
      acetylated hexose carbohydrates using ferrocene boronate (F(c)Bor) derivatization
      was developed. The biologically important N-acetyl hexosamines can be readily
      distinguished utilizing this technique. The analysis is made possible by
      utilizing the inherent electrochemical properties of the electrospray device to
      produce oxidized, pre-formed single-electron ferrocenyl ions in a non-aqueous
      solvent system. The electrospray device was modified using a custom built cell
      consisting of concentric stainless steel tubes, which produced an enhanced signal
      for the molecular ion of each analyte species. The MS(2) spectra derived from
      isomeric populations of ferrocenyl boronic esters of these carbohydrates when
      generated under the same conditions possessed features unique to each sugar
      allowing easy differentiation between a number of N-acetyl hexosamine isomers.

PMID- 10931539
TI  - Mechanism of negative ion formation from phenol and para-chlorophenol by
      interaction with free electrons
AB  - Dissociative electron attachment (DEA) to phenol and para-chlorophenol in the
      energy range 0-12 eV is studied. Analogies in formation of the resonance states
      in an ionic benzene and its derivatives are found to arise from the similarity of
      the aromatic base of the molecules. Differences in DEA processes are defined
      mainly by the influence of the functional OH-group and, to a lesser degree, by
      the presence of a chlorine atom. A correlation between the energies of the
      resonance states and ionization energies of p-chlorophenol and phenol, analogous
      to that found previously for phenol, is proved. On this basis it is established
      that the dominating mechanism for formation of molecular negative ions at
      energies above 5 eV is Feshbach resonance.Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931540
TI  - Selective detection of nitrated polycyclic aromatic hydrocarbons by electrospray
      ionization mass spectrometry and constant neutral loss scanning.
AB  - The development of a method for selective detection of nitrated polycyclic
      aromatic hydrocarbons (nitro-PAHs) among other polycyclic aromatic compounds
      (PACs) is described. The method is based on electrospray ionization mass
      spectrometry (ESI-MS), performed with a triple quadrupole analyzer and constant
      neutral loss (CNL) scanning. When subjected to ESI conditions, nitro-PAHs give
      rise to M(-), [M - H](-) and [M - H + 16](-) ions, which in turn produce
      fragments by losing 30 u, most probably NO. Other PACs do not undergo such
      fragmentations, and these differences can be exploited for selective detection of
      nitro-PAHs among other PACs. Nitro-PAHs can therefore be monitored through the
      loss of 30 u occurring under negative ion mode ESI conditions. Toward the full
      development of a screening method for nitro-PAHs, this article first discusses
      some general aspects of the negative ion mode full-scan ESI mass spectra obtained
      for these compounds and other PAH derivatives. Because the extent of observation
      of the loss of 30 u is sensitive to the ESI conditions used, the effects of
      ionization parameters such as solvent used, declustering voltage, and solvent
      flow rate are evaluated and discussed. Setting these parameters is very
      important, especially when interfacing a high performance liquid chromatography
      (HPLC) system with the ESI source of a triple quadrupole mass spectrometer.
      Preliminary results of on-line microbore HPLC/ESI-MS separations of PAC standards
      are presented, and elution/ionization conditions discussed.

PMID- 10931541
TI  - Thermochemical determination of the structure of negative ions on the basis of
      data from resonance electron capture mass spectrometry. Phenol, its chlorinated
      derivatives and a thioanalogue
AB  - Appearance energies for [M - H](-) ions from phenol (I), 4-chlorophenol (II),
      pentachlorophenol (III) and pentachlorothiophenol (IV) were measured. The
      following thermochemical data were deduced from experiment: DeltaH(acid) values
      of 343.3, 335.7, 317.1 and 317.1 kcal mol(-1) for RH molecules (I, II, III, and
      IV, respectively) and electron affinities (EAs) of R(.) free radicals 2.55, 2.90,
      3.79, and 3.65 eV, respectively. Our data for phenol (I) and 4-chlorophenol (II)
      demonstrate a higher stabilization of ArO(-) anions than was previously accepted.
      Using the enthalpic shift procedure for molecules and a series of isodesmic
      reactions for free radicals, earlier elaborated by the authors, a new Delta$bf
      H_bf fbf 0$ values for the following gas-phase species were obtained (kcal mol(
      1)): C(6)Cl(5)Br (5.0), C(6)Cl(5)SH (8.5), p-ClC(6)H(4)C(.) (2. 0), C(6)Cl(5)C(.)
      (-15), C(6)Cl(5)S(.) (44). Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931542
TI  - Direct determination of chlorpyrifos and its main metabolite 3,5, 6-trichloro-2
      pyridinol in human serum and urine by coupled-column liquid
      chromatography/electrospray-tandem mass spectrometry.
AB  - A rapid and sensitive automated coupled-column liquid chromatography/electrospray
      tandem mass spectrometry (LC/LC/ES-MS/MS) method has been developed for the
      quantitation of chlorpyrifos and 3,5,6-trichloro-2-pyridinol (TCP) in both human
      serum and urine. Human serum was first protein precipitated with acetonitrile,
      while urine was directly injected into the coupled-column system. A 10 microL
      aliquot was then analyzed using as first separation column a Discovery C18 5
      microm 50 x 2.1 mm; the fraction containing the analyte was transferred on-line
      to the second column consisting of a ABZ+ 5 microm 100 x 2.1 mm, which was
      connected to the electrospray source (Z-spray) of a Quattro LC triple-quadrupole
      instrument. Chlorpyrifos was detected in positive ion mode using four multi
      reaction monitoring (MRM) transitions while TCP was measured in negative ion mode
      using three pseudo-MRM transitions. The clean-up performed by the coupled-column
      approach avoids the use of an internal standard for the correct quantitation of
      both analytes, and the highly automated procedure renders a sample throughput of
      more than 100 samples per day. Both compounds can be determined using the same
      set-up, the only difference in the procedure being the composition of the first
      mobile phase. The method has proved to be fast, reliable and sensitive, yielding
      calibration curves for both analytes with correlation coefficients greater than
      0.9995. The repeatability and reproducibility at 5 and 50 ng/mL was lower than
      8%. The accuracy and precision were evaluated by means of recovery experiments
      from fortified serum (5-50 ng/mL) and urine (1-10 ng/mL) samples, obtaining
      satisfactory recoveries for both compounds (87-113% in serum, and 98-109% in
      urine), with coefficients of variation (CVs) less than 10%. The detection limits
      were similar for chlorpyrifos and metabolite: 1.5 ng/mL in serum, and 0.5 ng/mL
      in urine, where no sample handling took place. The validated procedures provide
      excellent tools for the specific assessment of occupational exposure to the
      organophosphorus pesticide chlorpyrifos, throughout the analysis of both human
      serum and urine, and it is more selective and sensitive than the current assay
      based on the measurement of the decrease in the cholinesterase activity.

PMID- 10931543
TI  - Identification of self-assembly products from N-phosphoamino acids by
      electrospray ionization mass spectrometry
AB  - The self-assembly products of N-(O,O'-diisopropyl)-L-alpha-amino acids in aqueous
      media, N-(O,O'-diisopropyl)phosphoryl dipeptides and tripeptides, were identified
      by electrospray ionization mass spectrometry. A stepwise fragmentation of the [M
      + H](+) ions from the C-terminus of N-phosphopeptides was observed. Copyright
      2000 John Wiley & Sons, Ltd.

PMID- 10931544
TI  - Observation of apigenin anionic clusters in the gas phase
AB  - The ubiquity and favorable medicinal properties of flavonoids make essential the
      determination of flavonoid levels in various matrices. While developing a liquid
      chromatography/tandem mass spectrometry method for the analysis of the flavonoid,
      apigenin, anionic oligomers and nitrate- and chloride-bound clusters of this
      compound were observed. Tandem mass spectrometry of these oligomers and cluster
      ions showed the cleavage of apigenin molecules from the precursor. The
      observation of these cluster ions shows the possibility of post-column
      derivatization techniques to enhance specificity in analysis. Copyright 2000 John
      Wiley & Sons, Ltd.

PMID- 10931545
TI  - Evidence of gold-gold intra- and intermolecular interactions gained by laser
      desorption/ionisation and fast atom bombardment mass spectrometry in the study of
      some gold(I) coordination compounds
AB  - The mass spectrometric behaviour of some two-coordinated linear gold(I) complexes
      has been studied by fast atom bombardment (FAB) and laser desorption/ionisation
      (LDI) methods. The results obtained demonstrate some interesting aspects of Au-Au
      interactions. The detection under FAB conditions of Au(n)(+) clusters, in
      particular of Au(3)(+) species, can be rationalised by the presence of
      significant intramolecular Au-Au interactions, while the formation under LDI
      conditions of Au(n)(+) clusters can be considered indicative of Au(ellipsis)Au
      intermolecular interactions present in the solid state. Copyright 2000 John Wiley
      & Sons, Ltd.

PMID- 10931546
TI  - Stable carbon and oxygen isotopic analysis of carbon monoxide in natural waters.
AB  - Techniques have been developed to allow on-line simultaneous analysis of
      concentration and stable isotopic compositions ((13)C and (18)O) of dissolved
      carbon monoxide (CO) in natural water, using continuous-flow isotope ratio mass
      spectrometry (CF-IRMS). The analytical system consisted sequentially of a He
      sparging bottle of water, a gas dryer, CO(2)-trapping stage using both Ascarite
      trap and silica-gel packed gas chromatography (GC), on-line oxidation to CO(2)
      using the Schutze reagent, cryofocusing, GC purification using a capillary column
      and measurement by CF-IRMS. Each sample analysis takes about 40 minutes. The
      detection limit with delta(13)C standard deviation of 0.5 per thousand is 300
      pmol and that with delta(18)O deviation of 1.0 per thousand is 750 pmol.
      Analytical blanks associated with these methods are 21+/-9 pmol. The procedures
      are evaluated through analyses of temporally varying concentration and isotopic
      compositions of CO in an artificial lake on the university campus. The delta(13)C
      and delta(18)O values of CO showed wide variation in accordance with diurnal
      variation of CO concentration, probably due to significant isotopic effects
      during photochemical production and microbial oxidation of CO in the aquatic
      environment. The delta(13)C and delta(18)O values of CO should be a useful tool
      in studies of the mechanism and pathways of CO production and consumption in
      natural waters.

PMID- 10931547
TI  - Matrix-assisted laser desorption/ionisation time-of-flight characterisation of
      biodegradable aliphatic copolyesters
AB  - Matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) and the
      off-line size exclusion chromatography matrix-assisted laser
      desorption/ionisation (SEC/MALDI) method has been applied to the structural
      characterisation and the molar mass (MM) determination of a series of
      biodegradable copolyesters synthesised by high temperature melt polycondensation
      reaction, and of two commercial copolyesters with the trade name Bionolle. The
      MALDI-TOF spectra of these copolymers showed the presence of cyclic oligomers in
      the lower mass region, in accord with expectations from polycondensation
      kinetics, and the presence of all linear species expected from their method of
      synthesis. The presence of unexpected linear species with olefin and carboxyl as
      end groups suggested the occurrence of undesirable thermal degradation processes
      during the melt polycondensation reaction. The absolute average molar masses
      obtained by the SEC-MALDI method turned out to be lower, by a factor of about two
      for succinate/adipate copolymers, and by a factor of three for succinate/sebacate
      copolymers, with respect to those computed by using polystyrene standards in SEC.
      Furthermore, the MALDI-TOF spectra of SEC fractions allowed not only the
      detection of linear and cyclic oligomers contained in these samples, but also the
      simultaneous determination of the average molar mass of both cyclic and linear
      oligomers. Due to the smaller hydrodynamic volume of cyclic chains with respect
      to linear ones, the ratio (M( cycle)/M( linear))( Ve) at a fixed elution volume
      was found to be 1.25, in good agreement with the theoretical value of 1.24.
      Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931548
TI  - Laser desorption/ionization coupled to tandem mass spectrometry for real-time
      monitoring of paraquat on the surface of environmental particles.
AB  - Aerosol mass spectrometry with laser desorption/ionization was investigated as a
      possible tool for real-time monitoring of the presence of the pesticide paraquat
      on the surface of airborne soil particles. Laser desorption/ionization of
      paraquat dication produced only singly charged ions. The most abundant species
      were [M](+.), [M - H](+), and [M - CH3](+). Operation of the ion trap mass
      spectrometer in the MS(3) mode allowed the reduction of the signal dependence on
      laser fluence fluctuations and permitted the detection of the analyte with good
      sensitivity and high selectivity. The estimated limit of detection in terms of
      surface coverage was 0.016 monolayers, approximately 1 attomole of paraquat on
      the surface of a single micron-sized soil particle.

PMID- 10931549
TI  - Oligosaccharide profiling: the facile detection of mono-, di- and
      oligosaccharides by electrospray orthogonal time-of-flight mass spectrometry
      using 3-aminophenylboronic acid derivatization.
AB  - Monosaccharides, disaccharides and larger carbohydrates can be derivatized using
      3-aminophenylboronic acid (3-APBA). This procedure is carried out at low pH (2.7
      3.0) and allows the use of positive ion mode electrospray orthogonal time-of
      flight mass spectrometry (ES-OTOFMS) to analyze the resulting boronate complexes.
      A carbohydrate profile map of a complex carbohydrate mixture, honey, was prepared
      which displayed superior sensitivity when compared with lithium ion
      cationization. Complexes formed using simple mono- and disaccharides show that
      facile in situ derivatization leads to an equilibrium mixture; which is
      reproducible for a specific set of electrospray conditions. D-Glucose could be
      detected at 5 microM concentration using the standard instrument spray interface.
      Lower detection levels of approximately 500 nM could be achieved using a
      nanospray device. The 3-APBA complexes are observed on instruments employing a
      low temperature interface (140-150 degrees C) which allows formation of the
      boronate species while still promoting efficient desolvation of the ions. The
      spectral identification of 3-APBA complexed carbohydrates in complex mixtures is
      facilitated by the easily observed 1 mass unit separated peak pair bearing the
      1:4 ratio resulting from the natural isotopic abundance of (10)B and (11)B.

PMID- 10931550
TI  - Detection of microcystins using electrospray ionization high-field asymmetric
      waveform ion mobility mass spectrometry/mass spectrometry.
AB  - A combination of electrospray ionization, high-field asymmetric waveform ion
      mobility spectrometry, and mass spectrometry (ESI-FAIMS/MS) was used to analyze
      standard solutions of microcystins-LR, -RR, and -YR. The ability of FAIMS to
      separate ions in the gas phase reduced the amount of background in the mass
      spectrum without compromising the absolute signal for these microcystins. This
      reduction in background resulted in a ten-fold improvement in the signal-to
      background ratio over conventional ESI-MS. Detection limits, using direct
      infusion, were determined to be 4, 2, and 1 nM for microcystins-LR, -RR, and -YR,
      respectively.

PMID- 10931551
TI  - A new gas inlet system for an isotope ratio mass spectrometer improves
      reproducibility
AB  - We have developed a new inlet system for a gas sample isotope ratio mass
      spectrometer (IRMS). It is based on the well-known open split design from the gas
      chromatography/mass spectrometry (GC/MS) system due to its simplicity. The
      advantages over the conventional double inlet system with the metal bellows
      design include an improved reproducibility mainly due to a highly controllable
      pressure and temperature adjustment, a markedly lowered memory effect due to an
      uninterrupted gas flow through the ion source which limits adsorption/desorption
      processes on surfaces, and a single inlet capillary circumventing problems of
      asymmetrical behavior of sample and reference inlet paths. Furthermore, sample
      consumption is of the same order as for conventional measurements (i.e. about 0.4
      mmol per hour), of which however only 2 &mgr;mol/h is used for the actual isotope
      ratio determination since the major gas amount acts as a gas flow seal against
      the atmosphere, corresponding to a 100-200 fold overkill. This may be improved in
      future systems. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931552
TI  - CO(2) concentration measurements on air samples by mass spectrometry
AB  - A new technique for measuring CO(2) concentration in air samples, based on mass
      spectrometry, is described as an alternative to the common gas chromatographic
      method. Using a dual inlet isotope ratio mass spectrometer (IRMS), the ratio of
      the abundances of the m/z peaks 44 and 28 is determined. The precision of
      measurements (standard deviation <3 ppmv) is generally as good as the analysis
      with gas chromatography for small air samples (<1 ml STP of air). A major
      advantage of this new method is the possibility of parallel elemental and
      isotopic measurements of many air components. The technique is further improved
      by new wide mass range mass spectrometers allowing simultaneous intensity
      measurements of several m/z values between 28 and 44, resulting in an uncertainty
      of <0.5 ppm. The precision is somewhat limited by the production of N(2)O and
      NO(2) from N(2) and O(2) in the ion source, which accounts for about half of the
      signal strength at m/z 44. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931553
TI  - A comparative study of laser spray and electrospray
AB  - A comparative study of electrospray and laser spray has been undertaken from
      various aspects. In general, laser spray gave stronger ion signals than
      electrospray, for solutions with the sample concentration of </=10(-5)M. For an
      aqueous solution of arginine, ion intensities of the cluster ions
      H(+)(arginine)(n) with larger n were observed by laser spray than by
      electrospray. This may be due to the enrichment of the sample concentration by
      the selective vaporization of the solvent from the meniscus of the sample
      solution effusing out of the stainless steel capillary by the laser irradiation.
      For an H(2)O/CH(3)OH (1:1, v/v) solution of 10(-5) M Arg-Lys-Arg-Ala-Arg-Lys-Glu,
      laser spray gave stronger ion signals than electrospray while the most highly
      charged ion observed was [M + 4H](4+) for laser spray and [M + 5H](5+) for
      electrospray. Laser spray was found to be the most suitable for the analyses of
      aqueous solutions. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10931554
TI  - Tyrosinase-induced cross-linking of tyrosine-containing peptides investigated by
      matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - Tyrosinase-induced oxidation of tyrosine is known to lead to melanin by cross
      linking of 5,6-dihydroxyindole (DHI) and indole-5,6-quinone intermediates.
      However, tyrosinase-induced cross-linking of tyrosine-containing peptides has not
      been reported. We observed tyrosinase-induced adducts of tyrosine-containing
      peptides by matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry (MALDI-TOFMS). MALDI-TOFMS was also used to observe tyrosine adducts
      at various levels of oxidation derived from acid hydrolysis of the peptide
      adducts. The rate of tyrosinase-induced browning of lys-tyr-lys was about half of
      that of tyrosine. These results indicate that tyrosinase-induced browning of
      tyrosine-containing peptides via direct oxidation and cross-linking of the
      benzene ring of the tyrosine residue occurs at a significant rate and needs to be
      considered in melanogenesis.

PMID- 10931555
TI  - Engineered protein scaffolds for molecular recognition.
AB  - The use of so-called protein scaffolds has recently attracted considerable
      attention in biochemistry in the context of generating novel types of ligand
      receptors for various applications in research and medicine. This development
      started with the notion that immunoglobulins owe their function to the
      composition of a conserved framework region and a spatially well-defined antigen
      binding site made of peptide segments that are hypervariable both in sequence and
      in conformation. After the application of antibody engineering methods along with
      library techniques had resulted in first successes in the selection of functional
      antibody fragments, several laboratories began to exploit other types of protein
      architectures for the construction of practically useful binding proteins.
      Properties like small size of the receptor protein, stability and ease of
      production were the focus of this work. Hence, among others, single domains of
      antibodies or of the immunoglobulin superfamily, protease inhibitors, helix
      bundle proteins, disulphide-knotted peptides and lipocalins were investigated.
      Recently, the scaffold concept has even been adopted for the construction of
      enzymes. However, it appears that not all kinds of polypeptide fold which may
      appear attractive for the engineering of loop regions at a first glance will
      indeed permit the construction of independent ligand-binding sites with high
      affinities and specificities. This review will therefore concentrate on the
      critical description of the structural properties of experimentally tested
      protein scaffolds and of the novel functions that have been achieved on their
      basis, rather than on the methodology of how to best select a particular mutant
      with a certain activity. An overview will be provided about the current
      approaches, and some emerging trends will be identified. (c) 2000 John Wiley &
      Sons, Ltd. Abbreviations used: ABD albumin-binding domain of protein G APPI
      Alzheimer's amyloid beta-protein precursor inhibitor BBP bilin-binding protein
      BPTI bovine (or basic) pancreatic trypsin inhibitor BSA bovine serum albumin CBD
      cellulose-binding domain of cellobiohydrolase I CD circular dichroism Cdk2 human
      cyclin-dependent kinase 2 CDR complementarity-determining region CTLA-4 human
      cytotoxic T-lymphocyte associated protein-4 FN3 fibronectin type III domain GSH
      glutathione GST glutathione S-transferase hIL-6 human interleukin-6 HSA human
      serum albumin IC(50) half-maximal inhibitory concentration Ig immunoglobulin IMAC
      immobilized metal affinity chromatography K(D) equilibrium constant of
      dissociation K(i) equilibrium dissociation constant of enzyme inhibitor LACI-D1
      human lipoprotein-associated coagulation inhibitor pIII gene III minor coat
      protein from filamentous bacteriophage f1 PCR polymerase-chain reaction PDB
      Protein Data Bank PSTI human pancreatic secretory trypsin inhibitor RBP retinol
      binding protein SPR surface plasmon resonance TrxA E. coli thioredoxin

PMID- 10931556
TI  - Drug-DNA recognition: energetics and implications for design.
AB  - In this article we review thermodynamic studies designed to examine the
      interaction of low molecular weight ligands or drugs with DNA. Over the past 10
      years there has been an increase in the number of rigorous biophysical studies of
      DNA-drug interactions and considerable insight has been gained into the
      energetics of these binding reactions. The advent of high-sensitivity
      calorimetric techniques has meant that the energetics of DNA-drug association
      reactions can be probed directly and enthalpic and entropic contributions to the
      binding free energy established. There are two principal consequences arising
      from this type of work, firstly three-dimensional structures of DNA-drug
      complexes from X-ray and NMR studies can be put into a thermodynamic context and
      the energetics responsible for stabilizing the observed structures can be more
      fully understood. Secondly, any rational approach to structure-based drug design
      requires a fundamental base of knowledge where structural detail and
      thermodynamic data on complex formation are intimately linked. Therefore these
      types of studies allow a set of general guidelines to be established, which can
      then be used to develop drug design algorithms. In this review we describe recent
      breakthroughs in duplex DNA-directed drug design and also discuss how similar
      principles are now being used to target higher-order DNA molecules, for example,
      triplex (three-stranded) and tetraplex (four-stranded) structures.

PMID- 10931558
TI  - Molecular similarity analysis between insect juvenile hormone and N, N-diethyl-m
      toluamide (DEET) analogs may aid design of novel insect repellents.
AB  - Molecular similarity analysis of stereoelectronic properties between natural
      insect juvenile hormone (JH), -a synthetic insect juvenile hormone mimic (JH
      mimic, undecen-2-yl carbamate), and N, N-diethyl-m-toluamide (DEET) and its
      analogs reveals similarities that may aid the design of more efficacious insect
      repellents and give a better insight into the mechanism of repellent action. The
      study involves quantum chemical calculations using the AM1 semi-empirical
      computational method enabling a conformational search for the lowest and most
      abundant energy conformers of JH, JH-mimic, and 15 DEET compounds, followed by
      complete geometry optimization of the conformers. Similarity analyses of
      stereoelectronic properties such as structural parameters, atomic charges, dipole
      moments, molecular electrostatic potentials, and highest occupied molecular
      orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies were
      performed on JH, JH-mimic and the DEET compounds. The similarity of
      stereoelectronic attributes of the amide/ester moiety, the negative electrostatic
      potential regions beyond the van der Waals surface, and the large distribution of
      hydrophobic regions in the compounds appear to be the three important factors
      leading to a similar interaction with the JH receptor. The similarity of
      electrostatic profiles beyond the van der Waals surface is likely to play a
      crucial role in molecular recognition interaction with the JH receptor from a
      distance. This also suggests electrostatic bioisosterism of the amide group of
      the DEET compounds and JH-mimic and, thus, a model for molecular recognition at
      the JH receptor. The insect repellent property of the DEET analogs may thus be
      attributed to a conflict of complementarity for the JH receptor binding sites.

PMID- 10931557
TI  - Binding of nascent collagen by amyloidogenic light chains and amyloid
      fibrillogenesis in monolayers of human fibrocytes.
AB  - Light (L) chain dimers expressed by multiple myeloma cells and collected as Bence
      Jones proteins from the urine of human subjects were tested for their ability to
      form deposits in fibroblast monolayer cell cultures. Bence-Jones proteins from
      subjects with primary amyloidosis associated with L chains were shown to form
      fibrillar deposits by the in vitro assay introduced in this report. Filaments
      interspersed with nascent collagen could be detected after only 48 h. Deposition
      of L chains continued over a period of 72 h culminating in the appearance of
      dense fibrils with widths of 80-100 A and a variety of lengths. Formation of
      amyloid-like fibrils was accompanied by interference with the maturation of the
      collagen produced by the fibroblast cells. Fibrils composed of the Mcg lambda
      type L chain were deposited between collagen fibers, thus expanding them
      laterally and leading to their partial disintegration. Mature collagen was
      completely missing from fibroblast monolayers exposed to the Sea lambda chain and
      the Jen kappa chain. Collagen with the characteristic striped pattern matured
      normally in control samples, such as those not dosed with amyloid precursors or
      those treated with a non-amyloidogenic Bence-Jones protein (e.g., the Hud lambda
      chain dimer). By immunochemical techniques using fluorescein- and gold-labeled
      anti-L chain antibodies, amyloidogenic L chains were shown to decorate the
      strands of nascent collagen. This observation suggests that amyloidogenic L
      chains are concentrated in the extracellular matrix by monovalent antigen
      antibody type reactions. The capacity of the Mcg L chain dimer to bind collagen
      derived sequences was tested by soaking crystals with a collagenase substrate, PZ
      Pro-Leu-Gly-Pro-D-Arg. Difference Fourier analysis at 2.7 A resolution indicated
      that the PZ-peptide is a site-filling ligand. It could not be removed from the
      active site by perfusion of the crystal with ammonium sulfate crystallizing
      media. Similar experiments with the collagen-derived peptide (Pro-Pro-Gly)(5)
      showed substantial hysteresis effects extending from one end of the Mcg dimer to
      the other. After the ligand was withdrawn, the active site of the Mcg dimer could
      no longer bind the PZ-peptide. However, if the active site was first blocked by
      the PZ-peptide and subsequently exposed to the (Pro-Pro-Gly)(5) peptide, the
      difference Fourier map was indistinguishable from that obtained with the PZ
      peptide alone. We concluded that amyloidogenic L chains such as the Mcg dimer
      could be concentrated in the perivascular space by binding to normal tissue
      constituents. These components include nascent collagen, which can be deterred
      from maturing as a result of this binding. Participation in such pathological
      activity is also self-destructive to the amyloidogenic L chains, which lose their
      binding capabilities for collagen-derived peptides and also become susceptible to
      irreversible conversion to amyloid fibrils. All of these events may be prevented
      by prior treatment of the amyloidogenic L chains with site-filling ligands. (c)
      2000 John Wiley & Sons, Ltd.

PMID- 10931559
TI  - A Y2000 Update of Current Safety Issues Related to MRI.

PMID- 10931560
TI  - Safety of strong, static magnetic fields.
AB  - Issues associated with the exposure of patients to strong, static magnetic fields
      during magnetic resonance imaging (MRI) are reviewed and discussed. The history
      of human exposure to magnetic fields is reviewed, and the contradictory nature of
      the literature regarding effects on human health is described. In the absence of
      ferromagnetic foreign bodies, there is no replicated scientific study showing a
      health hazard associated with magnetic field exposure and no evidence for hazards
      associated with cumulative exposure to these fields. The very high degree of
      patient safety in strong magnetic fields is attributed to the small value of the
      magnetic susceptibility of human tissues and to the lack of ferromagnetic
      components in these tissues. The wide range of susceptibility values between
      magnetic materials and human tissues is shown to lead to qualitatively differing
      behaviors of these materials when they are exposed to magnetic fields.
      Mathematical expressions are provided for the calculation of forces and torques.

PMID- 10931561
TI  - Review of patient safety in time-varying gradient fields.
AB  - In magnetic resonance, time-varying gradient magnetic fields (dB/dt) may
      stimulate nerves or muscles by inducing electric fields in patients. Models
      predicted mean peripheral nerve and cardiac stimulation thresholds. For gradient
      ramp durations of less than a few milliseconds, mean peripheral nerve stimulation
      is a safe indicator of high dB/dt. At sufficient amplitudes, peripheral nerve
      stimulation is perceptible (i.e., tingling or tapping sensations). Magnetic
      fields from simultaneous gradient axes combine almost as a vector sum to produce
      stimulation. Patients may become uncomfortable at amplitudes 50%-100% above
      perception thresholds. In dogs, respiratory stimulation has been induced at about
      300% of mean peripheral nerve thresholds. Cardiac stimulation has been induced in
      dogs by small gradient coils at thresholds near Reilly's predictions. Cardiac
      stimulation required nearly 80 times the energy needed to produce nerve
      stimulation in dogs. Nerve and cardiac stimulation thresholds for dogs were
      unaffected by 1.5-T magnetic fields.

PMID- 10931562
TI  - Radiofrequency energy-induced heating during MR procedures: a review.
AB  - During an MR procedure, most of the transmitted RF power is transformed into heat
      within the patient's tissue as a result of resistive losses. Not surprisingly,
      the primary bioeffects associated with the RF radiation used for MR procedures
      are directly related to the thermogenic qualities of this electromagnetic field.
      This review article discusses the characteristics of RF energy-induced heating
      associated with MR procedures, with an emphasis on thermal and other physiologic
      responses observed in human subjects.

PMID- 10931563
TI  - Auditory noise associated with MR procedures: a review.
AB  - This review article discusses the various types of acoustic noise produced during
      the operation of MR systems, describes the characteristics of the acoustic noise,
      and presents information regarding noise control techniques. In addition, the
      problems related to acoustic noise for patients and healthcare workers are
      discussed.

PMID- 10931564
TI  - Sensitivity and power deposition in a high-field imaging experiment.
AB  - Image signal-to-noise ratio and power dissipation are investigated theoretically
      up to 400 MHz. While the text is mathematical, the figures give insights into
      predictions. Hertz potential is introduced for probe modeling where charge
      separation cannot be ignored. Using a spherical geometry, the potential from
      current loops that would produce a homogeneous static B1 field is calculated; at
      high frequency it is shown to create an unnecessarily inhomogeneous field.
      However, a totally homogeneous field is shown to be unattainable. Boundary
      conditions are solved for circularly polarized fields, and strategies for limited
      shimming of the sample B1 field are then presented. A distinction is drawn
      between dielectric resonance and spatial field focusing. At high frequency, the
      region of maximum specific absorption is shown to move inside the sample and
      decrease. From the fields in both rotating frames, the signal-to-noise ratio is
      derived and compared with the traditional, low-frequency formulation. On average,
      it is mostly found to be slightly larger at high frequency. Nevertheless, the
      free induction decay is sometimes found to be annulled.

PMID- 10931565
TI  - SAR and temperature changes in the leg due to an RF decoupling coil at
      frequencies between 64 and 213 MHz.
AB  - Specific absorption rate (SAR) due to a butterfly surface coil in a realistic
      model of the leg was calculated for frequencies 64 < or = v < or = 213 MHz. The
      resulting temperature distribution and temperature changes (deltaT) were found
      using the bioheat transfer equation. To compare results at different frequencies,
      the minimum B-field within the coil's footprint in the plane parallel to the coil
      but displaced 50 mm from it was kept constant. To achieve the same minimum B
      field as that associated with operation at 64 MHz that was compliant with safety
      guidelines (peak SAR in 1 cm3 of tissue of 2.3 W/kg), it was predicted that SAR
      would exceed recommended levels when v > or = 149 MHz. The corresponding maximum
      deltaT at 64, 128, and 213 MHz were 0.3, 1.3, and 5.0 degrees C, respectively.

PMID- 10931566
TI  - Safety of MRI-guided endovascular guidewire applications.
AB  - Magnetic radiofrequency (RF) fields applied during magnetic resonance imaging
      (MRI) may induce heating in devices made from conductive materials. The present
      paper reports on theoretical and experimental studies on the RF heating resonance
      phenomenon of an endovascular guidewire. A nitinol-based guidewire was inserted
      into a vessel phantom and imaged at 1.5 and 0.2 T with continuous temperature
      monitoring at the guidewire tip. The heating effects due to different
      experimental settings were examined. A model is developed for the resonant
      current and the associated electric field produced by the guidewire acting as an
      antenna. Temperature increases of up to 17 degrees C were measured while imaging
      the guidewire at an off-center position in the 1.5 T MR system. Power absorption
      produced by the resonating wire decreased as the repetition time was increased.
      No temperature rise was measured at 0.2 T. Considering the potential utility of
      low-field, open MR systems for MRI-guided endovascular interventions, it is
      important to be aware of the safety of such applications.

PMID- 10931567
TI  - Heating around intravascular guidewires by resonating RF waves.
AB  - We examined the unwanted radiofrequency (RF) heating of an endovascular guidewire
      frequently used in interventional magnetic resonance imaging (MRI). A Terumo
      guidewire was partly immersed in an oblong saline bath to simulate an
      endovascular intervention. The temperature rise of the guidewire tip during an
      FFE sequence [average specific absorption rate (SAR) = 3.9 W/kg] was measured
      with a Luxtron fluoroscopic fiber. Starting from 26 degrees C, the guidewire tip
      reached temperatures up to 74 degrees C after 30 seconds of scanning. Touching
      the guidewire may cause sudden heating at the point of contact, which in one
      instance caused a skin burn. The excessive heating of a linear conductor like the
      guidewire can only be explained by resonating RF waves. The capricious
      dependencies of this resonance phenomenon on environmental factors have severe
      consequences for predictability and safety guidelines.

PMID- 10931568
TI  - RF transmit power limit for the barewire loopless catheter antenna.
AB  - The safety of the barewire loopless catheter antenna in transmit mode is
      addressed with respect to radiofrequency (RF) heating. Analytical expressions for
      electric field and specific absorption rate (SAR) distributions surrounding the
      antenna are postulated and experimentally verified. Limiting RF transmit power to
      40-70 mW time-averaged power, depending on the specific antenna design, will
      ensure that the current regulatory guideline of SAR of 8 W/kg in any gram of
      tissue is not exceeded. These limits can act as guidelines for the design of RF
      pulses for use with this device. Further study is required to examine the safety
      of the antenna in receive mode.

PMID- 10931569
TI  - Pre-MRI procedure screening: recommendations and safety considerations for
      biomedical implants and devices.
AB  - Maintaining a safe MR environment is a daily challenge for MR healthcare workers,
      especially in consideration of the increasing number of clinical MR applications
      and the large and growing variety of biomedical implants and devices that are
      currently used in patients. This review article presents policies and procedures
      that should be used to screen all patients and individuals before allowing them
      to enter the magnetic resonance (MR) environment. Information pertaining to MR
      safety and the relative risk factors for implants, devices and materials is
      discussed. A comprehensive pre-MRI procedure screening form that is recommended
      for use by MR facilities is also included.

PMID- 10931570
TI  - Aneurysm clips: evaluation of magnetic field interactions with an 8.0 T MR
      system.
AB  - This study was conducted to evaluate magnetic field interactions for aneurysm
      clips exposed to an 8.0 T magnetic resonance (MR) system. Twenty-six different
      aneurysm clips were tested for magnetic field translational attraction
      (deflection angle test) and torque (qualitative assessment method) using
      previously described techniques. Six of the specific aneurysm clips (i.e. type,
      model, blade length) made from stainless steel alloy (Perneczky) and Phynox
      (Yasargil, models FE 748 and FE 750) displayed deflection angles above 45 degrees
      and torque measurements of +4, indicating that these aneurysm clips maybe unsafe
      for patients or individuals in an 8.0 T MR environment. The specific aneurysm
      clips (i.e. type, model, blade length) made from commercially pure titanium
      (Spetzler), Elgiloy (Sugita), titanium alloy (Yasargil, model FE 750T), and MP35N
      (Sundt) displayed deflection angles less than 45 degrees and torque that ranged
      from + 1 to +4. Accordingly, these aneurysm clips are likely to be safe for
      patients or individuals exposed to an 8.0 T MR system. Depending on the actual
      dimensions and mass, an aneurysm clip made from Elgiloy may or may not be
      acceptable for a patient or individual in the 8.0 T MR environment.

PMID- 10931571
TI  - MR evaluation ex vivo and in vivo of a covered stent-graft for abdominal aortic
      aneurysms: ferromagnetism, heating, artifacts, and velocity mapping.
AB  - Magnetic resonance imaging (MRI) safety was evaluated at 1.5 T in a covered
      nickel titanium stent-graft (Vanguard) used for endovascular treatment of
      abdominal aortic aneurysms (AAAs). Imaging artifacts were assessed on MRI with
      contrast-enhanced (CE) three-dimensional (3D) MR angiography (MRA) and spiral
      computed tomography (CT) in 10 patients as well as ex vivo. Velocity mapping was
      performed in the suprarenal aorta and femoral arteries in 14 patients before and
      after stent-graft placement. For comparison it was also performed in six healthy
      volunteers. No ferromagnetism or heating was detected. Metal artifacts caused
      minimal image distortion on MRI/MRA. The artifacts disturbed image evaluation on
      CT at the graft bifurcation and graft limb junction. No significant differences
      in mean flow were found in patients before and after stent-graft placement. Our
      study indicates that MRI at 1.5 T may be performed safely in patients with the
      (Vanguard) stent-graft. MRI/MRA provides diagnostic image information. Velocity
      mapping is not included in our routine protocol.

PMID- 10931572
TI  - Subchronic in vivo effects of a high static magnetic field (9.4 T) in rats.
AB  - The potential adverse biologic effects of sub chronic (cumulatively 10 weeks)
      exposure to a high magnetic field (9.4 T) were evaluated in young adult male and
      female Fischer rats as well as in their progeny. Biologic end points in adult
      rats included changes in daily clinical observations; spatial memory tests;
      weekly heart rates, body weights, food and water consumption, and the feed
      efficiency ratio; terminal hematologic, blood biochemical and urinary parameter
      changes; gross pathologic findings; and major organ weights. In offspring,
      biologic end points included the gestation period, number of live births, number
      of pups, ratio of male to female pups/litter; postnatal time period of eye
      opening; birth and weekly body weights, behavioral changes, central nervous
      system responses, as well as hematologic, blood biochemistry, and urinary
      parameter changes; and gross pathologic findings. Findings from this study showed
      that there were no adverse biologic effects in male and female adult rats or
      their progeny that could be attributed to 10-week exposure to a 9.4-T static
      magnetic field.

PMID- 10931573
TI  - Biological effects of long-duration, high-field (4 T) MRI on growth and
      development in the mouse.
AB  - The effects of long-duration, high-field magnetic resonance imaging (MRI) on
      fetal growth and postnatal development in mice were studied. Seven experimental
      groups of pregnant ICR mice were exposed for 9 hours on day 9 and/or day 12 post
      coitus (pc) to magnetic fields (4 T static, 5 T/sec switched gradient, and 0.2
      W/kg radiofrequency at 170 MHz) associated with MRI conditions. Two experimental
      groups (sham and exposure groups) were exposed to a combination of ultrasound
      (day 9 pc, 3.25 MHz, focused) and MRI-associated fields (day 12 pc). No
      statistically significant changes in fetal growth were observed in the animals
      exposed to only MRI or ultrasound fields. However, in the combined ultrasound and
      MRI-exposed group, the fetal weight and crown-rump length were reduced compared
      with the sham and cage controls. These results suggest that MRI and ultrasound
      exposure well in excess of current clinical conditions can exert biological
      effects if applied at sensitive stages of fetal development.

PMID- 10931574
TI  - In vitro evaluation of teratogenic effects by time-varying MR gradient fields on
      fetal human fibroblasts.
AB  - The purpose of this study was to evaluate the influence on fetal cell growth in
      vitro of rapidly changing magnetic gradient fields such as those produced by the
      gradient coils of a typical magnetic resonance (MR) imager. The static magnetic
      field and the radiofrequency pulses were disabled during all measurements. Human
      fetal fibroblasts were placed within a specially designed MR-compatible
      incubation system inside the magnet. Trapezoid-shaped waveforms of 500 and 75 Hz
      base frequency and an amplitude of 2 mT were applied for 2-24 hours.
      Proliferation of the cells was monitored for 3 weeks after exposure. Cell cycle
      analysis was performed until 24 hours after exposure to detect alterations in
      cell division. Tests were performed under two different conditions of growth to
      detect increased as well as decreased proliferation effects. None of these tests
      showed differences in proliferation and cell cycle distribution between exposed
      and nonexposed cells.

PMID- 10931575
TI  - Sound-level measurements and calculations of safe noise dosage during EPI at 3 T.
AB  - This paper describes systematic methods for measuring and controlling sound
      levels within a magnetic resonance scanner. The methods are illustrated by
      application to the acoustic noise generated by a 3 T scanner during echoplanar
      imaging (EPI). Across five measurement sessions, sound pressure levels at the
      center of the head gradient coil ranged from 122 to 131 dB SPL [123 to 132
      dB(A)]. For protection against damaging noise exposure, UK and US industrial
      guidelines stipulate that the maximum permitted daily noise dosage is equivalent
      to 90 dB(A) for 8 hours, where noise dosage is a function of the level of an
      acoustic signal and the length of exposure to it. Without hearing protection,
      this equivalent level would be exceeded by less than 5 seconds of exposure to the
      measured levels of scanner acoustic noise. These findings highlight the
      importance of noise reduction and hearing protection for those exposed to the
      acoustic noise generated during EPI.

PMID- 10931576
TI  - Spiral scan peripheral nerve stimulation.
AB  - Time-varying magnetic fields induce electric fields that can cause physiological
      stimulation. Stimulation has been empirically characterized as a function of
      dB/dt and duration based on experiments using trapezoidal and sinusoidal gradient
      waveforms with constant ramp time, amplitude, and direction. For two-dimensional
      (2D) spiral scans, the readout gradient waveforms are frequency- and amplitude
      modulated sinusoids on two orthogonal axes in quadrature. The readout gradient
      waveform therefore rotates with amplitude and angular velocity that are generally
      not constant. It does not automatically follow that spiral stimulation thresholds
      can be predicted using available stimulation models. We scanned 18 normal
      volunteers with a 2D spiral scan and measured global thresholds for axial,
      sagittal, and coronal planes. We concluded that the stimulation model evaluated
      accurately predicts slew rate-limited spiral mean stimulation thresholds, if the
      effective ramp time is chosen to be the half-period at the end of the spiral
      readout.

PMID- 10931577
TI  - Potential MR hazard to patients with metallic heart valves: the Lenz effect.
AB  - The Lenz effect on the motion of metal containing moving parts of artificial
      heart valves has not been considered to date. In this paper the basic theory is
      outlined and a simple model applied to estimate worst-case forces on such valves.
      The results indicate a potential for forces over 100 times greater than for the
      more widely recognized ferromagnetic interation. Resistive pressure effects
      comparable to cardiac pressure differences may occur for such valves in the
      mitral position even at fields as low as 1.5 T. The effect will increase linearly
      with field strength. Additional monitoring and perhaps even exclusion of such
      patients may be prudent, even at 1.5 T.

PMID- 10931578
TI  - EEG-triggered functional MRI in patients with pharmacoresistant epilepsy.
AB  - Functional magnetic resonance imaging (fMRI) triggered by scalp
      electroencephalography (EEG) recordings has become a promising new tool for
      noninvasive epileptic focus localization. Studies to date have shown that it can
      be used safely and that highly localized information can be obtained. So far, no
      reports using comprehensive clinical information and/or long-term follow-up after
      epilepsy surgery in a larger patient group have been given that would allow a
      valuable judgment of the utility of this technique. Here, the results of 11
      patients with EEG-triggered fMRI exams who also underwent presurgical evaluation
      of their epilepsy are given. In most patients we were able to record good quality
      EEG inside the magnet, allowing us to trigger fMRI acquisition by interictal
      discharges. The fMRI consisted of echoplanar multislice acquisition permitting a
      large anatomical coverage of the patient's brain. In 8 of the 11 patients the
      exam confirmed clinical diagnosis, either by the presence (n = 7) or absence (n =
      1) of focal signal enhancement. In six patients, intracranial recordings were
      carried out, and in five of them, the epileptogenic zone as determined by fMRI
      was confirmed. Limitations were encountered a) when the focus was too close to
      air cavities; b) if an active epileptogenic focus was absent; and c) if only
      reduced cooperation with respect to body movements was provided by the patient.
      We conclude that EEG-triggered fMRI is a safe and powerful noninvasive tool that
      improves the diagnostic value of MRI by localizing the epileptic focus precisely.

PMID- 10931581
TI  - Implantable pulse generators (pacemakers) and electrodes: safety in the magnetic
      resonance imaging scanner environment.
AB  - Static magnetic fields, time-varying electric and magnetic fields, and
      electromagnetic interference within the magnetic resonance imaging scanner
      environment can cause the implantable pulse generator (pacemaker) to malfunction
      and render the electrodes hazardous to the patient. This article provides a
      review of the literature and of international regulatory guidance concerning
      safety considerations when these implantable devices are exposed to magnetic
      resonance imaging.

PMID- 10931580
TI  - Safety of MR scanning in patients with nonferromagnetic aneurysm clips.
AB  - The purpose of this study was to report our surveillance of patients with
      nonferromagnetic aneurysm clips (NFAC) who have undergone magnetic resonance
      imaging (MRI). Forty-six patients with NFAC underwent MRI over a 7-year period.
      Medical records were studied for evidence of subjective or objective clinical
      findings as a result of the MRI scan. In two patients with subjective complaints,
      computed tomograms (CT) were reviewed and patient interviews conducted. No
      significant neurologic signs or longterm symptoms were experienced. Two patients
      did not complete their MRI scans due to transient unilateral head pain in one and
      head "pressure" in another. CT scans in these patients demonstrated no evidence
      for hemorrhage or visible change in clip position. We documented no objective
      adverse outcome of patients undergoing MRI with NFAC, confirming that MRI can be
      performed safely in patients with nonferromagnetic aneurysm clips. The cause of
      subjective complaints in two of our patients is unknown.

PMID- 10931579
TI  - Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI
      in adults: results of the U.S. multicenter phase III clinical trials (safety).
AB  - The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in
      546 adults with known or suspected focal liver lesions. An initial contrast
      enhanced computed tomography examination was followed by unenhanced magnetic
      resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI.
      Adverse events were reported for 23% of the patients; most were mild to moderate
      in intensity, did not require treatment, and were not drug related. The most
      commonly reported adverse events were nausea (7%) and headache (4%). The
      incidence of serious adverse events was low (nine events in six patients) and not
      drug related. Injection-associated discomfort was reported for 69% of the
      patients, and the most commonly reported discomforts included heat (49%) and
      flushing (33%). Changes in laboratory values and vital signs were generally
      transient, were not clinically significant, and did not require treatment. There
      were no clinically significant short-term risks from exposure to MnDPDP.

PMID- 10931582
TI  - Safety of approved MR contrast media for intravenous injection.
AB  - In the last 10 years, the use of intravenous contrast media in magnetic resonance
      (MR) has become well-established clinical practice. Contrast media provide
      critical additional diagnostic information in many instances. The gadolinium
      chelates constitute the largest group of MR contrast media and are considered to
      be very safe. These agents are thought to be safer than nonionic iodinated
      contrast agents. Unlike x-ray agents, the gadolinium chelates are not
      nephrotoxic. Minor adverse reactions, including nausea (1%-2% for all agents) and
      hives (<1% for all agents), occur in a very low percent of cases. Health care
      personnel should be aware of the (extremely uncommon) potential for severe
      anaphylactoid reactions in association with the use of MR contrast media and be
      prepared should complications arise. The four gadolinium chelates currently
      available worldwide, gadopentetate dimeglumine, gadoteridol, gadodiamide, and
      gadoterate meglumine, cannot be differentiated on the basis of adverse reactions.
      Far fewer patients have been examined to date with the two other agents that have
      widespread approval, mangafodipir trisodium and ferumoxides. These latter two
      agents are considered to be very safe but have a higher percentage of associated
      adverse reactions (7%-17% with mangafodipir trisodium and 15% with ferumoxides).
      This review discusses the safety issues involved with administration of
      intravenous contrast media in MR imaging, focusing on the six agents (four
      gadolinium chelates, one manganese chelate, and the last a large iron particle)
      with widespread use world-wide.

PMID- 10931583
TI  - Implantable spinal fusion stimulator: assessment of MR safety and artifacts.
AB  - The objective of this investigation was to perform magnetic resonance (MR)
      imaging safety and artifact testing of an implantable spinal fusion stimulator.
      Magnetic field interactions, artifacts, and operational aspects of an implantable
      spinal fusion stimulator were evaluated in association with a 1.5 T MR system.
      Magnetic field-related translational attraction was measured using the deflection
      angle test. A special test apparatus was used to determine torque at 4.7 T.
      Artifacts were characterized using fast multiplanar spoiled gradient-echo, T1
      weighted spin-echo, and T1-weighted fast spin-echo sequences. Operational aspects
      of the implantable spinal fusion stimulator before and after exposure to MR
      imaging at 1.5 T were assessed. In addition, nine patients (six lumbar spine and
      three cervical spine) with implantable spinal fusion stimulators underwent MR
      imaging. The findings indicated that magnetic field interactions were relatively
      minor, artifacts were well characterized and should not create diagnostic
      problems, and there were no changes in the operation of the spinal fusion
      stimulator. The nine patients underwent MR procedures without substantial adverse
      events or complaints. Based on the results of this investigation and in
      consideration of the findings from previous studies of MR imaging safety for the
      implantable spinal fusion stimulator, MR imaging may be performed safely in
      patients using MR systems operating at 1.5 T or less following specific
      recommendations and precautions.

PMID- 10931584
TI  - Perfusion magnetic resonance imaging of the lung: characterization of pneumonia
      and chronic obstructive pulmonary disease. A feasibility study.
AB  - Perfusion magnetic resonance (MR) imaging is a promising new method for detection
      of perfusion defects in the diagnosis of pulmonary embolism. In the present study
      we evaluated the first-pass characteristics of perfusion MR imaging in patients
      with pneumonia or chronic obstructive pulmonary disease (COPD), frequent
      differential diagnoses to pulmonary embolism. Dynamic contrast-enhanced MR images
      of 12 patients with acute pneumonia and 13 patients with exacerbation of COPD
      were acquired in both the coronal and transaxial planes (an inversion recovery
      prepared gradient-echo sequence using 0.05 mmol/kg gadodiamide/injection). The MR
      images and the signal intensity (SI) versus time curves were characterized for
      each disease entity and compared with normal lung and the findings in pulmonary
      embolism from our previous study. The perfusion MR images of pneumonia showed
      distinct regions of increased contrast enhancement; in COPD with signs of
      emphysema (11 of the 13 COPD patients), the images showed a coarse pattern of
      reduced contrast enhancement. The SI versus time curves of pneumonia, COPD with
      signs of emphysema, and normal lung were statistically different, the respective
      pooled SI values (+/-95% CI) being as follows: mean baseline SI, 20.7 (1.1), 7.4
      (0.4), and 8.5 (0.3); mean peak SI, no peak, 12.9 (1.5), and 27 (4.6); and mean
      max change of SI in percent, 110 (27), 79 (22), and 205 (52). Perfusion MR
      imaging of pneumonia and COPD with signs of emphysema showed first-pass that were
      characteristics promising for diagnostic use. Both the MR images and the SI
      versus time curves were different from the perfusion characteristics in normal
      lung and pulmonary embolism shown previously.

PMID- 10931585
TI  - A multicenter validation of an active contour-based left ventricular analysis
      technique.
AB  - Quantitative analysis of functional cardiac magnetic resonance (MR) images has
      been limited by the lack of well-validated, semiautomatic, methods for rapid
      analysis. We describe the evaluation of a DICOM-compatible PC-based parallel
      processing tool, for cardiac magnetic resonance analysis (CAMRA), which supports
      semiautomatic image mensuration using an active contour model-based algorithm.
      The CAMRA software was used to analyze data from 12 patients in a multicenter
      acquisition and analysis trial to compare semiautomatic contour detection with
      manual planimetry of the left ventricular endocardium from short-axis, breath
      held, cine gradient-echo images. There was excellent agreement between the manual
      and semiautomatic measurements of global left ventricular function, with no
      significant (P = 0.32) difference in the determination of ejection fraction (-0.9
      +/- 3.1% [mean difference +/- 1 standard deviation]). There was no significant
      interobserver difference in the semiautomatically measured ejection fraction.
      Additionally, a single observer completed the analysis on data from 30 patients
      and found no significant (P = 0.05) difference in the determination of ejection
      fraction (-1.3 +/- 3.5% [mean difference +/- 1 standard deviation]). The CAMRA
      software demonstrates the capability for the reproducible evaluation of global
      left ventricular function in cardiac patients, with adequate interobserver
      reproducibility for use in multicenter trials.

PMID- 10931586
TI  - Changes in left and right ventricular cardiac function after valve replacement
      for aortic stenosis determined by cine MR imaging.
AB  - The purpose of this study was to determine the changes in function of both the
      left and the right ventricles (LV, RV) before and after aortic valve replacement
      (AVR), compared with age-matched healthy volunteers using magnetic resonance (MR)
      imaging. Fourteen patients with aortic stenosis underwent MR imaging (1.5 T)
      before and 3 (n = 14) and 12 (n = 9) months after surgical valve replacement. An
      electrocardiographically triggered two-dimensional cine fast low-angle shot
      sequence was used for the evaluation of absolute values and indices related to 1
      m(2) body surface area for function, mass, and LV wall thickening. Fourteen age
      matched healthy volunteers served as controls. Before surgery, all patients
      showed significant abnormalities of LV mass and function, whereas RV mass and
      function were not different from those of volunteers and remained mostly
      unchanged. After surgery, normalization of LV ejection fraction, absolute mass,
      and end-systolic wall thickness was observed, whereas the LV mass index failed to
      normalize, and LV volumes remained elevated. Aortic stenosis combined with a
      significant, but not severe reduction in LV function only affects the LV, whereas
      the RV remains unaffected at this stage of disease. AVR leads to improved LV
      function and reduced hypertrophy, but without normalization of LV volumes or the
      LV mass index within 1 year.

PMID- 10931587
TI  - Characterization of experimental spinal cord injury with magnetization transfer
      ratio histograms.
AB  - This study was designed to characterize the severity of tissue damage in
      experimental spinal cord injury using magnetization transfer (MT) histogram
      analysis. Seven Sprague-Dawley rats were subjected to laminectomy and standard
      weight-drop injury to the spinal cord (four rats at 15 cm drop-height and three
      rats at 2.5 cm). Three control animals underwent laminectomy without weight-drop.
      After sacrifice, the animals were scanned at 1.9 T with a pulsed off-resonance MT
      technique. Following magnetic resonance (MR) imaging, the cords were embedded in
      paraffin and sectioned into 5-microm sections for semiquantitative
      histopathological analysis. Composite histograms were generated using data
      spanning an axial distance of 3 cm centered on the injury site. MT histogram
      parameters, such as the amount of tissue with statistical correspondence to
      normal white matter, were highly predictive of histopathological results,
      including myelination state and neurofilament damage. Less correlation with edema
      was observed, suggesting that the technique was most sensitive to true tissue
      alteration.

PMID- 10931588
TI  - Apparent diffusion coefficient in thoracolumbar intervertebral discs of healthy
      young volunteers.
AB  - Apparent diffusion coefficient values (ADC) of healthy intervertebral discs of
      young volunteers in the thoracolumbar spine were determined using a single-shot
      EPI sequence. ADC(z) was in the lumbar spine slightly higher than ADC(x) or
      ADC(y). In vivo diffusion measurements of intervertebral discs may offer a novel
      diagnostic tool to evaluate disc diseases in early phases.

PMID- 10931589
TI  - MRI with mangafodipir trisodium in the detection and staging of pancreatic
      cancer.
AB  - The purpose of this study was to compare prospectively computed tomography (CT)
      and magnetic resonance (MR) imaging before and after mangafodipir trisodium
      infusion for the detection and staging of focal pancreatic lesions. From November
      1996 to October 1997, 43 consecutive patients suspected to have a focal
      pancreatic lesion were included in a phase III study. Triphasic helical CT was
      performed, as well as MRI at 1.5 T, as follows: axial T1-weighted (T1w) turbo
      spin echo (TSE), spectral presaturation with inversion recovery (SPIR) T1w TSE,
      T1w turbo field echo (TFE), and SPIR T2w TSE before and after mangafodipir
      trisodium (0.01 mmol/ml, 0.5 ml/kg) infusion. Imaging results were correlated
      with surgery, laparoscopy, laparoscopic ultrasound, and biopsy. Objective
      measurements were performed by measuring signal intensities (SIs) of lesion and
      parenchyma and calculating contrast indexes (CIs) and contrast-to-noise-ratios
      (CNRs) to assess the delineation of the tumor. SIs were correlated with four
      phantom standards with a known SI. Thirty-eight pancreatic adenocarcinomas were
      present, as well as one cystadenoma, two papillomas, and two cases of focal
      pancreatitis. SI measurements revealed significant increases in CIs for the
      lesion compared with the parenchyma in T1w TSE (69.7 vs 152.7; P = 0. 0003) and
      T1w TFE (107.8 vs 194.2; P = 0.0002). These series also revealed significant
      increases in CNRs (for T1w TSE: 9.7 vs 13.0; P = 0.0407 and for T1w TFE: 14.5 vs
      26.1; P = 0.0001). In the other series, there was no significant increase. CT
      detected 38 lesions, MRI without mangafodipir trisodium detected 39 lesions, and
      MRI with mangafodipir trisodium detected 40 lesions, giving detection accuracy
      rates of 88%, 91%, and 93%, respectively. Staging accuracy rates for vascular
      ingrowth were 81%, 75%, and 81%, respectively. Overall staging accuracy rates
      were 57%, 54%, and 54%, respectively, mostly due to undetected small metastases
      in the peritoneum, omentum, or liver (< 1 cm). This study indicates that a) MRI
      after mangafodipir trisodium gives a better delineation of the tumor in T1w
      series, but b) does not significantly improve the detection rate and staging
      accuracy of focal pancreatic lesions over MRI without this contrast medium.

PMID- 10931590
TI  - Extrahepatic abdominal imaging in patients with malignancy: comparison of MR
      imaging and helical CT in 164 patients.
AB  - The purpose of this study was to compare the performance of magnetic resonance
      (MR) imaging using currently available techniques with contrast-enhanced single
      phase helical computed tomography (CT) in depicting extrahepatic disease in
      patients with malignancy. At two institutions, 164 patients with known or
      suspected malignancy underwent abdominal imaging with contrast-enhanced helical
      CT and MR imaging. The prospective interpretations of the CT scans and MR
      examinations were used to assess the sensitivity of each imaging test in
      detecting benign and malignant extrahepatic disease at 17 anatomic sites. Imaging
      findings were compared with results of surgery in 57 patients and with the
      combined results of image-guided biopsy, follow-up cross-sectional imaging
      studies, other concurrent imaging tests, and clinical follow-up. For the 164
      patients, helical CT scans depicted 221 of 316 (70%) sites of proven extrahepatic
      tumor compared with 288 sites (91%) (P < 0.0001) for MR imaging. For the 57
      patients who underwent exploratory laparotomy, helical CT scans depicted 101 of
      154 (66%) findings of surgically confirmed extrahepatic tumor compared with MR
      imaging, which depicted 139 sites (90%) (P < 0.0001). Anatomic sites at which MR
      imaging showed a significantly greater detection of extrahepatic tumor included
      the peritoneum, bowel, and vascular and osseous structures. For depiction of
      benign extrahepatic disease, there was no significant difference between helical
      CT and MR imaging. MR imaging, using currently available T1-weighted, RARE T2
      weighted, and gadolinium-enhanced imaging, is effective in depicting extrahepatic
      disease in patients with malignancy. Compared with single-phase helical CT
      scanning, MR imaging shows an advantage in depicting tumor involving the
      peritoneum, omentum, bowel, and osseous and vascular structures.

PMID- 10931591
TI  - Reversibility of experimental acute renal failure in rats: assessment with USPIO
      enhanced MR imaging.
AB  - The purpose of this study was to evaluate the potential reversibility of kidney
      lesions in an experimental model of acute renal failure using ultra-small
      particles of iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging. This
      study was conducted in 21 uninephrectomized rats using a model of iodinated
      contrast media-induced renal failure. Thirteen rats received selective
      intraarterial renal administration of diatrizoate (370 mg/ml) and were compared
      with two control groups, including six animals injected with saline and two
      noninjected animals. MR imaging was performed 28 hours, 8 days, and 22 days after
      the procedure. Each MR session included axial and coronal T1- and coronal T2
      weighted images before and after intravenous administration of 60 micromol Fe/kg
      of USPIO. The rats were sacrificed immediately after the last MR session for
      pathologic evaluation. MR images were qualitatively and quantitatively
      interpreted with respect to pathologic data, and differences were statistically
      studied. At day 22, histology showed 4 severely diseased kidneys with focal areas
      of necrosis, 5 mildly diseased kidneys with tubular vacuolization, and 12 normal
      kidneys. On quantitative data, a high correlation between the percentage of
      negative enhancement and histologic data was observed (P < 0.05). Qualitative
      interpretation showed a sensitivity and specificity of USPIO-enhanced T2-weighted
      MR images of 88% and 91%, respectively. Follow-up enhancement curves showed a
      constant increase of intrarenal USPIO negative enhancement in normal kidneys
      between day 1 and day 22, whereas all severely involved kidneys displayed higher
      USPIO negative enhancement at day 1 without significant changes over time until
      day 22. USPIO may be useful for in vivo follow-up of the reversibility of
      experimentally induced iodinated contrast media renal impairment in animals.

PMID- 10931592
TI  - In vivo measurements of relaxivities in the rat kidney cortex.
AB  - The aim of this study was to implement a novel noninvasive method to derive the
      in vivo T1 relaxivity (R1) and T2 relaxivity (R2) in the rat kidney cortex. A two
      compartment gadolinium diethylene triamine pentaacetic acid (Gd-DTPA)
      distribution model was established to estimate the bolus and infusion dosages of
      Gd-DTPA necessary for obtaining the required steady-state concentration levels.
      After a single bolus injection of (99m)Tc-DTPA, several blood samples were
      collected. Based on considerations from the applied two-compartment model, a
      steady-state concentration was predicted approximately 5-10 minutes after the
      bolus injection. The plasma concentration levels of Gd-DTPA were measured by
      simultaneous injection of (99m)Tc-DTPA. Three regions in the cortex (upper,
      central, and lower) of both rat kidneys were used. A statistical evaluation
      resulted in the following in vivo relaxivities found at 7 T: R1 = 1.04 +/- 0.08
      mM(-1)s(-1) and R2 = 10.78 +/- 0.83 mM(-1)s(-1). Using a 95% confidence interval,
      no intracortical differences were detected. The relaxivities R1 and R2 calculated
      in the intact rat kidney cortex were distinctly different from relaxivities found
      in human plasma: (22 degrees C) 4.42 +/- 0.07 mM(-1)s(-1) (r2> 0.98) and R2 =
      5.75 +/- 0.17 mM(-1)s(-1) (r2> 0.98), respectively. The measurements showed a
      marked difference between in vitro and in vivo relaxivities. Comparison of the
      distribution rates in pig, human, and rats shows a distinct proportionality
      between size and renal function.

PMID- 10931593
TI  - Colon diseases: MR evaluation using combined T2-weighted single-shot echo train
      spin-echo and gadolinium-enhanced spoiled gradient-echo sequences.
AB  - This study demonstrates the appearance of large bowel diseases on magnetic
      resonance (MR) images using breath-hold T2-weighted half-Fourier acquisition
      snapshot turbo spin-echo (HASTE), breath-hold T1-weighted spoiled gradient-echo
      (SGE), and breath-hold gadolinium-enhanced T1-weighted SGE with and without fat
      suppression sequences. The study represents a collective experience using a
      generalized combined abdominal-pelvic imaging protocol. Of 29 patients, 27 had
      surgical, endoscopic, microbiological, and/or histopathological correlation, and
      2 had a diagnosis based on characteristic imaging findings. Fifteen patients had
      neoplastic disease including colon adenocarcinoma (n = 11), rectosigmoid
      carcinoid (n = 1), familial adenomatous polyposis (n = 2), and cecal lipoma (n =
      1). Fourteen patients had non-neoplastic disease including diverticulosis (n =
      6), ischemic colitis (n = 2), pseudomembranous colitis (n = 2), acute
      appendicitis with periappendiceal abscess (n = 2), Mycobacterium avium
      intracellulare (MAI) colitis (n = 1), and Crohn's proctocolitis (n = 1). In all
      15 patients with neoplastic diseases, MR imaging depicted the primary lesions and
      demonstrated local extent. Mass lesions were best shown on T2-weighted HASTE and
      gadolinium-enhanced fat-suppressed SGE images. Of 14 patients with non-neoplastic
      diseases, inflammatory changes were best shown on gadolinium-enhanced fat
      suppressed T1-weighted SGE images in all cases. MR imaging with fast scanning
      breath-hold techniques and intravenous gadolinium enhancement provided good
      depiction and characterization of large bowel diseases.

PMID- 10931594
TI  - Acquired generalized lipoatrophy (AGL): highly selective MR lipid imaging and
      localized (1)H-MRS.
AB  - Frequency-selective chemical shift magnetic resonance (MR) imaging was applied on
      the calf musculature and the abdomen of a patient with acquired generalized
      lipoatrophy (AGL; Lawrence syndrome), a very rare syndrome affecting selectively
      several types of adipose tissue accompanied by alterations in glucose and energy
      metabolism. In addition, (1)H-MRS was used for assessment of intra- (IMCL) and
      extramyocellular lipid stores (EMCL) in the skeletal musculature of the calf.
      Results from the AGL patient were compared with an age-matched group of five
      healthy volunteers. Fat-selective imaging of the calf revealed a total lack of
      subcutaneous adipose tissue. No EMCL signal was found in the spectra from the
      soleus muscle of the AGL patient. IMCL signals were present in the spectra but
      were clearly lower than in the controls (14% of normal value in the soleus
      muscle). In abdominal images, subcutaneous fat signal was not detectable, as in
      the calf, but nearly normal conditions were shown for visceral adipose tissue
      between abdominal organs. Fat-selective images showed the liver with high signal
      intensity, indicating hepatic steatosis combined with hepatosplenomegaly. Modern
      chemical shift-selective MR imaging and localized spectroscopy allow a
      noninvasive and quantitative assessment of tissue composition in patients with
      disorders of carbohydrate and lipid metabolism.

PMID- 10931595
TI  - New image contrast mechanisms in intermolecular double-quantum coherence human MR
      imaging.
AB  - We have developed a novel magnetic resonance imaging (MRI) method based on the
      intermolecular double-quantum coherence (DQC) in humans. Combined quantum
      mechanical and classical formalisms were used to characterize the signal and to
      aid in the design of a DQC imaging sequence with conventional or echoplanar
      acquisitions. Imaging contrast was evaluated in volunteers using a 1.5-T clinical
      scanner. The results demonstrated that the DQC images have contrasts
      fundamentally different from the conventional images based on single-quantum
      coherence (SQC). Both our theoretical analysis and experiments suggest that
      signals from DQCs have a higher signal-to-noise ratio than those from zero
      quantum coherence (ZQC) for human brain imaging. The new contrast in DQC imaging
      may be useful for the detection of varying microstructures, potentially improving
      the detection of tumors without the need for contrast agents and providing a
      higher sensitivity and selectivity to magnetic susceptibility distributions in
      functional MRI brain studies.

PMID- 10931596
TI  - Three-dimensional, time-resolved (4D) relative pressure mapping using magnetic
      resonance imaging.
AB  - We describe here a method for generating relative pressure maps from magnetic
      resonance velocity data in three spatial and one temporal dimension (4D). The
      relative pressure map calculated for pulsatile flow in a compliant phantom was
      shown to be consistent with independent pressure transducer measurements. The
      feasibility of performing 4D pressure mapping in vivo is also demonstrated.

PMID- 10931597
TI  - MR-based temperature monitoring for hot saline injection therapy.
AB  - We applied magnetic resonance (MR) phase mapping methods to monitor the thermal
      frequency shift of water in order to study temperature changes from percutaneous
      hot saline injection therapy (PSIT) using in vitro swine livers and in vivo
      rabbit livers. The thermal coefficients calculated from the shifts of the water
      frequency with thermocouple based temperature measurements were -0.0085 +/-
      0.0019 ppm/ degrees C for the in vitro studies and -0.0089 ppm/ degrees C for the
      in vivo studies. The error range was estimated to be +/- 3 degrees C and +/- 4.5
      degrees C, respectively. Color-coded temperature maps were compared with
      macroscopic lesion sizes of the specimen. Regions defined using a 20 degrees C
      elevation in the initial images following hot saline injection (around 55 degrees
      C in absolute temperature) closely correlated with visible coagulation in size.
      We conclude that MR temperature monitoring of PSIT is quite feasible and may be
      helpful in expanding the clinical use of this thermal therapeutic tool for liver
      tumors.

PMID- 10931598
TI  - Role of magnetic resonance in the diagnosis of subclavian steal syndrome.
AB  - Subclavian steal syndrome (SSS) is a condition secondary to an occlusion in the
      proximal subclavian artery, in which the blood supply to the arm is sustained by
      reversal of flow in the ipsilateral vertebral artery. We describe two similar
      cases of SSS due to a right aortic arch with isolated left subclavian artery.
      Diagnosis was made with magnetic resonance imaging (MRI) and angiography (MRA),
      which was confirmed by Doppler ultrasound and X-ray angiography. The exact
      anatomic relationships of the vascular structures were well demonstrated on
      contrast-enhanced MRA, while flow reversal was documented on flow-encoded MRI
      datasets. We conclude that the combination of different MRI modalities forms an
      accurate and reliable alternative in the diagnostic workup of patients with
      suspected SSS.

PMID- 10931599
TI  - Echoplanar imaging in GI clinical practice: assessment of gastric emptying and
      antral motility in four patients.
AB  - Gastric emptying, frequency of antral contractions, and speed of antral
      contraction propagation were assessed in four patients using echoplanar imaging
      techniques. The results obtained and their impact on the diagnosis and management
      of the patients are presented and discussed. This shows that echoplanar
      evaluation of gastric function is noninvasive, well-tolerated by patients,
      detects clinically relevant abnormalities, and has the potential of becoming a
      valuable examination in the clinical gastrointestinal practice.

PMID- 10931600
TI  - Improved 3D quantitative mapping of blood volume and endothelial permeability in
      brain tumors.
AB  - We describe a new method to allow simultaneous mapping of endothelial
      permeability and blood volume in intracranial lesions. The technique is based on
      a tumor leakage profile during the first pass (fp) of contrast bolus calculated
      from the time-dependent plasma-contrast concentration function (PCCF) in three
      dimensional (3D) T1-weighted dynamic studies. The performance of the method has
      been evaluated by comparing results with those obtained from more conventional
      methods in patients with primary brain neoplasms. The new permeability maps
      (k(fp)) are visually compatible with those calculated using a conventional
      multicompartment model (k(tran)). Quantitatively, the new maps are free from
      overestimation of k(tran) due to first-pass effects. The new blood volume maps,
      which segment out the contamination of contrast leakage, agree closely with maps
      derived from susceptibility studies. The new method is fast, robust, and easy to
      perform. The method is suitable for use in clinical environments and is likely to
      be of benefit where longitudinal assessment of treatment response is required.

PMID- 10931601
TI  - Synergistic effect between iron and gadolinium in MRI.
AB  - Different combinations of iron glycerophosphate (Fe) and gadolinium-diethylene
      triamine pentaacetic acid (DTPA) (Gd) were imaged with a three-dimensional (3D)
      gradient-recalled echo (GRE), a 2D GRE, and a HASTE sequence on a 1.5-T MR
      scanner. A combination of Fe and Gd results in a synergistic effect, which
      improves the signal gain for selective 3D imaging of the colon and simultaneously
      decreases the endoluminal signal on the HASTE and 2D GRE images for better
      visualization of water and Gd-enhanced structures in the gut wall.

PMID- 10931604
TI  - Direct stenting: is the future near?

PMID- 10931603
TI  - A randomized study of direct coronary stent delivery compared with stenting after
      predilatation: the NIR future trial. On behalf of the NIR Future Trial
      Investigators.
AB  - This randomized trial compared a strategy of direct stenting without
      predilatation (n = 39) with conventional stenting with predilatation (n = 42) in
      patients with suitable lesions in native vessels > or = 2. 5-mm diameter to be
      covered by either a 9- or 16-mm-length NIR Primo stent. Equipment cost [mean
      (median) +/- SD] was less in those with direct stenting [$1,199 (979) +/- 526]
      than in those with predilatation [$1,455 (1,285) +/- 401, P < 0.001]. There was
      no significant difference in contrast use or fluoroscopy time. Procedural time
      was shorter in the direct stenting group. The clinical outcome at 1 month was
      satisfactory in both groups. In selected patients, a strategy of direct stenting
      is feasible, costs less, and is quicker to perform than the conventional strategy
      of stenting following predilatation.

PMID- 10931602
TI  - Prosthetic heart valves: evaluation of magnetic field interactions, heating, and
      artifacts at 1.5 T.
AB  - The purpose of this study was to use ex vivo testing techniques to determine the
      magnetic resonance imaging (MRI) safety aspects for 32 different heart valve
      prostheses that had not been evaluated previously in association with the 1.5-T
      MR environment. Ex vivo testing was performed using previously described
      techniques for the evaluation of magnetic field interactions (deflection angle
      and torque), heating [gel-filled phantom and fluoroptic thermometry; 15 minutes
      of MRI at a specific absorption rate (SAR) of 1.1 W/kg], and artifacts (using
      gradient echo and T1-weighted spin-echo pulse sequences). Thirteen heart valve
      prostheses displayed interactions with the magnetic field. However, these
      magnetic field interactions were considered relatively minor. Heating was < or
      =0.8 degrees C for these implants. Artifacts varied from mild to severe depending
      on the amount and type of metal used to make the particular heart valve
      prosthesis. For these 32 different heart valve prostheses, the relative lack of
      substantial magnetic field interactions and negligible heating indicate that MR
      procedures may be conducted safely in individuals with these implants using MR
      systems with static magnetic fields of 1.5 T or less.

PMID- 10931605
TI  - Elective coronary stent implantation in cardiogenic shock complicating acute
      myocardial infarction: in-hospital and six-month clinical and angiographic
      results.
AB  - Effective treatment of patients with acute myocardial infarction and cardiogenic
      shock depends on restoring persistent patency of the infarct-related artery.
      Coronary stenting, reducing abrupt or delayed closure related to dissection and
      suboptimal result, may improve PTCA results in cardiogenic shock. Eighteen
      patients (14 males and 4 females, mean age 59 +/- 7 years), referred to
      catheterization laboratory for acute myocardial infarction and shock, had
      elective stent implantation during 14 primary and 4 rescue PTCA. Time delay
      between shock onset and PTCA was 4.1 +/- 3 hr (range, 30 min to 12 hr). The IRA
      was LAD in seven patients (38%), LCx in two (11%), and RCA in eight (45%). One
      patient (5.%) had distal LMCA occlusion. Stent deployment was successful in 100%
      of patients and resulted in TIMI 3 flow in 13 (72%) patients. In 13 (72%) cases,
      cardiogenic shock gradually resolved and the patients were discharged alive. Five
      patients (28%) died because of irreversible hemodynamic deterioration without
      evidence of reinfarction. At 6-month follow-up, all the discharged patients were
      alive and no patient had reinfarction or recurrent angina. Heart transplant was
      required in one patient 5 months after stenting because of refractory congestive
      heart failure. Angiography demonstrated patency of all the coronary arteries
      treated, with TIMI 3 flow in all patients. Stent restenosis rate was 30%, and
      target lesion revascularization with CABG or re-PTCA was not required in any
      case. LV function improved from 39% +/- 15% to 51% +/- 15% (P < 0.01). Elective
      coronary stenting is an effective treatment for acute myocardial infarction
      complicated by cardiogenic shock and may improve acute and long-term survival.

PMID- 10931606
TI  - Coronary stenting versus balloon angioplasty in small coronary artery with
      complex lesions.
AB  - The impact of stenting on small vessels (< 3.0 mm) with complex lesions (B2-C) is
      still controversial. Restenosis rate in this population is high (> 40%). We
      compared early and late outcome of patients with complex coronary lesions in
      small vessel treated with traditional coronary angioplasty (angioplasty group)
      and with elective stent implantation (stent group). Angioplasty group (n = 97)
      and stent group (n = 112) were comparable for all clinical and angiographic
      characteristics. All patients in the two groups had clinical and angiographic
      follow-up. Major adverse cardiac events (MACE) and restenosis rate were
      evaluated. No patients in the two groups experienced in-hospital death or bypass
      surgery. Myocardial infarction occurred in four patients in the angioplasty group
      and in seven patients in the stent group (P = 0.36). No patients in either the
      angioplasty or the stent group had acute stent thrombosis, whereas subacute stent
      thrombosis occurred in only one patients of the stent group (0.9%). Long-term
      MACEs (20 +/- 4 month) were not different in the two groups (angioplasty group
      39% vs. stent group 44%, P = 0.35). Target lesion revascularization rate was 33%
      in the angioplasty group and 34% in the stent group (P = 0.50). Restenosis rate
      was not statistically different in the two groups (stent group 41% vs.
      angioplasty group 38%, P = 0.41). In conclusion, compared to balloon angioplasty,
      elective stent implantation in small vessels with complex lesions does not
      improve early and late outcome. Cathet. Cardiovasc. Intervent. 50:390-397, 2000.

PMID- 10931607
TI  - High versus low-pressure balloon inflation during multilinktrade mark stent
      implantation: acute and long-term angiographic results.
AB  - We compared the impact of low and high-pressure balloon inflation on acute and
      late angiographic results of Multilink stent. Low-pressure balloon inflation (9.5
      +/- 1.9 atm) was used in 43 stents and high pressure (17.1 +/- 1.5 atm) in 44. A
      larger immediate luminal gain was achieved in stents with high-pressure balloon
      inflation (1.80 +/- 0.26 vs. 1.47 +/- 0.62; P = 0.002), resulting in a larger
      mean diameter in this group (2.71 +/- 0.37 vs. 2.48 +/- 0.47; P = 0.017). At
      follow-up, a larger luminal diameter was achieved in the high pressure group
      (1.93 +/- 0.72 vs. 1.45 +/- 0.66; P = 0.002) and a trend to a lower rate of
      angiographic restenosis (15% vs. 38%, P = 0.08).

PMID- 10931608
TI  - Low or high pressure for stent deployment? not always "in medio stat virtus".

PMID- 10931609
TI  - Side-branch occlusion after rotational atherectomy of in-stent restenosis:
      incidence, predictors, and clinical significance.
AB  - We evaluated the incidence, predictors, and clinical significance of side-branch
      occlusion (SBO) after rotational atherectomy (RA) for treatment of in-stent
      restenosis (ISR) and compared it with those of native coronary artery (NC). RA
      was performed in 64 patients with 34 ISR (42 side branches) and 30 NC (40 side
      branches). SBO occurred 14% after RA in ISR group compared with 0% in NC group (P
      < 0.05), and 33% after adjunctive balloon inflation in ISR group compared with
      2.5% in NC group (P < 0.01). Non-Q myocardial infarction developed in seven
      patients in ISR group and four patients in NC group (P = NS). The presence of
      significant side-branch (SB) ostial disease (OR = 4.7, P < 0.05) and ISR lesions
      (OR = 15.5, P < 0.05) were the only independent predictors of SBO by multivariate
      analysis. The incidence of SBO is higher after RA of ISR than RA of NC and may be
      associated with an increased risk of non-Q myocardial infarction.

PMID- 10931610
TI  - Bifurcation disease: to treat or not to treat.

PMID- 10931611
TI  - Long-term follow-up of pregnant women after percutaneous mitral valvuloplasty.
AB  - The aim of this study was to evaluate long-term clinical follow-up and
      echocardiographic data on pregnant patients with mitral stenosis who underwent
      percutaneous mitral valvuloplasty (PMV) in our center and the development of
      their infants. PMV has proven to be an effective alternative to treat pregnant
      patients with mitral stenosis. However, long-term outcome of these patients, as
      well as the potential harmful effects caused by radiation on their infants, still
      awaits to be determined. From January 1988 to February 1999, 30 pregnant women
      (mean gestational duration, 24.95 +/- 5.59 weeks) underwent PMV. Twenty-three
      (77%) were subsequently followed by a medical interview during 5.33 +/- 3.12
      years. Clinical variables such as NYHA functional class (FC), the need of a
      repeat PMV or surgical procedure, the presence of embolic events, and mortality
      rate were evaluated during follow-up. Mitral valve area, mean transmitral
      gradient, and the presence of mitral regurgitation were also assessed by Doppler
      echocardiography. Clinical data on the development of the infants were obtained
      from the assistant pediatricians. All patients were in NYHA FC III or IV before
      the procedure. During follow-up, 91% of them were in FC I and II. Two patients
      (9%) who had remained in FC III underwent a repeat successful PMV; no further
      surgery was required. There were no embolic events or death related to the
      procedure. Echocardiography showed an initial increase in mitral valve area from
      1.14 +/- 0.22 cm(2) to 2.01 +/- 0.21 cm+/- (P < 0.0001). During long-term follow
      up, it decreased to a mean of 1.75 +/- 0.24 cm(2) (P < 0. 0001). Initial
      transmitral valve gradient decreased from 17.73 +/- 4. 56 mm Hg to 5.91 +/- 1.80
      mm Hg (P = 0.0001) and 8.95 +/- 3.58 (P = 0.002) during long-term follow-up.
      Twenty one children (96%), aged 4. 91 +/- 2.8 years, showed normal growth and
      development, and no clinical abnormalities were observed. These favorable long
      term results suggests PVM to be the procedure of choice to treat pregnant women
      with mitral stenosis who remain in FC III or IV despite adequate medical therapy.
      No harmful effects due to the use of radiation were observed in the children.

PMID- 10931612
TI  - Percutaneous inoue balloon valvuloplasty is the procedure of choice for
      symptomatic mitral stenosis in pregnant women.

PMID- 10931613
TI  - The ESSEX (European Scimed Stent Experience) study.
AB  - The aim of the study was to assess the safety and feasibility of implantation of
      the Scimed Radius stent. Secondary objectives were to assess the result of stent
      placement by quantitative coronary angiography (QCA) and intravascular ultrasound
      (IVUS). The ESSEX study was a prospective, multicenter, observational study in
      which candidates for a single elective stent implantation, in a de novo or
      restenotic lesion, reference diameter 2.75-4.00 mm and target lesion < 14 mm in
      length, were enrolled. QCA at baseline, postprocedure, and 6-month follow-up was
      performed. IVUS was used to assess optimal stent implantation. One hundred and
      three patients were enrolled. Forty-four percent of the patients had unstable
      angina. Stent implantation was technically successful in all patients. Additional
      stents were implanted in 17 patients for procedural dissection (16) and spasm
      (1). Ninety-seven percent of patients were event-free at 1 month and 76% at 6
      month follow-up. Angiographic restenosis rates for de novo lesions and for all
      patients were 19% and 21%, respectively. Clinical events occurred at 1- and 6
      month follow-up in 2.9% and 24.3% of patients, respectively. No patients suffered
      subacute thrombosis. Retrospective analysis of peak balloon inflation pressure (<
      or = 12 and > 12 atm) as a determinant of clinical, QCA, and IVUS outcomes
      suggested no benefit or detrimental effect from optimization with high-pressure
      balloon inflation. Implantation of the self-expanding Radius stent is safe and
      efficacious. Based on registry data, clinical, angiographic, and IVUS, data
      comparable with modern balloon-expandable stents were obtained.

PMID- 10931615
TI  - Amplatzer device closure of a residual aortopulmonary window.
AB  - Significant residual defects after surgical closure of aortopulmonary windows
      have previously required re-operation. In this paper, we describe the use of a
      custom made Amplatzer closure device to occlude a hemodynamically significant
      defect in a 5-year-old child. The device was successfully deployed without
      complication, and resulted in a major reduction in aorto-pulmonary flow.

PMID- 10931616
TI  - 18-year experience with transseptal procedures through baffles, conduits, and
      other intra-atrial patches.
AB  - The presence of an intra-atrial patch (IAP) has been considered a relative
      contraindication to transseptal puncture (TSP). The purpose of this study is to
      determine the efficacy and safety of the TSP through baffles, conduits,
      pericardial patches and other prosthetic materials in the intra-atrial septum. We
      reviewed the records of all pediatric patients with IAP who underwent TSP at
      Texas Children's Hospital from November 1979 through February 1998. The review
      included the cardiac diagnoses, indications for TSP, technical difficulties and
      follow up echocardiograms specifically addressing residual atrial shunts A total
      of 1958 TSP were performed. Thirty-nine patients had IAP. Cardiac diagnoses in
      those 39 patients included D-transposition of the great arteries after Mustard
      (10) or Senning procedure (6), single ventricle variant post-Fontan operation
      (4), total anomalous venous return repair (4), atrioventricular canal repair (9)
      and atrial septal defect with patch repair (6). Patients' age ranged from 1-31
      years (median 7 years). The duration from the time of surgical repair to TSP
      ranged from 0.1-21 years (median 5 years). Indications for TSP included
      diagnostic and therapeutic intervention for pulmonary venous obstruction (12),
      creation of a baffle fenestration (2), prosthetic mitral valve evaluation (1),
      left ventricular outflow tract evaluation (1), access the left heart for
      hemodynamic evaluation (23). The IAP was traversed in 38/39 patients (97.5%),
      followed by diagnostic or therapeutic prograde left-heart catheterization. No
      complications were encountered. Follow up echocardiography in 30/38 PTS
      demonstrated no residual shunting across the atrial septum except for two cases
      in which the atrial baffle had been intentionally fenestrated. Transseptal
      puncture through an intra-atrial patch is a safe procedure. This technique is
      effective in permitting diagnostic and therapeutic left heart catheterization and
      does not result in residual shunting through the patch.

PMID- 10931614
TI  - Incidence of thrombocytopenia following coronary stent placement using abciximab
      plus clopidogrel or ticlopidine.
AB  - The incidence of thrombocytopenia with ticlopidine and clopidogrel when used in
      conjunction with abciximab has not been systematically addressed. We evaluated
      the rate of thrombocytopenia in patients undergoing intracoronary stent
      implantation receiving bolus plus infusion of abciximab and either ticlopidine or
      clopidogrel. We noted an incidence of 24% with the combination of 300-mg
      clopidogrel and abciximab. Other doses of ticlopidine (250 and 500 mg) and
      clopidogrel (75 mg) did not result in a statistically significant increase in
      thrombocytopenia over that of the 2.5%-5.2% reported incidence with abciximab
      alone. Length of hospital stay was 2.3 vs. 6.4 days in those developing
      thrombocytopenia (P = 0.06). Four (25%) developed thrombocytopenia requiring
      blood transfusion. Eight (50%) had no sequelae. The combination of 300-mg
      clopidogrel and abciximab results in a significant increase in the incidence of
      thrombocytopenia. This is an important clinical observation that merits further
      study.

PMID- 10931617
TI  - Transseptal puncture through an artificial material: A safe technique

PMID- 10931618
TI  - A new technique for endomyocardial biopsy in infants and small children.
AB  - Endomyocardial biopsy (EMB) is usually performed from the femoral veins in
      infants and small children. This requires the use of a long vascular sheath to
      direct a bioptome to the ventricular septum. We describe a technique of EMB in
      this population that obviates the need for the use of a long vascular sheath. A 5
      Fr 0.038" internal diameter, no-sideholes Cobra catheter (Cook, Bloomington, IN)
      introduced via a 5 Fr short sheath was used to direct a 3 Fr, 60-cm-length Cook
      bioptome to the ventricular septum. From January 1998 to August 1999, this
      technique was used 22 times in seven patients for EMB (median, age 13 months;
      range, 1-72 months). Indications for EMB in this group were posttransplantation
      surveillance (21 times) and evaluation for cardiomyopathy/myocarditis (1). Median
      number of EMB specimens obtained per procedure was 6 (range, 5-9). There was one
      pneumopericardium seen post-EMB with this technique without hemodynamic
      embarrassment. EMB in infants and small children can be performed successfully,
      safely, and repeatedly from the femoral veins without the need for a long sheath.

PMID- 10931619
TI  - Treatment of abdominal aortic pseudoaneurysm with covered stents in a pediatric
      patient.
AB  - An occasional complication of redilating stents placed in children is false
      aneurysm. We report the use of covered stents to treat a false aneurysm of the
      abdominal aorta in an adolescent girl with neurofibromatosis and abdominal
      coarctation of the aorta.

PMID- 10931620
TI  - Interventional treatment of lateral tunnel dehiscence in a total cavopulmonary
      connection using a balloon expandable covered stent.
AB  - In this paper we present a patient with dehiscence of an intra-atrial tunnel
      previously constructed during a total cavopulmonary connection procedure. We
      describe the use of a custom made covered stent to seal off the dehisced segment,
      and abolish the intra-cardiac shunting. We believe this is the first account of
      such a procedure being undertaken.

PMID- 10931621
TI  - Cutting balloon angioplasty for the treatment of in-stent restenosis.
AB  - The results using the Cutting Balloon for the treatment of in-stent restenosis
      may be superior to those of conventional percutaneous transluminal coronary
      angioplasty (PTCA) or even the combination of PTCA preceded by rotational
      atherectomy. The reasons for these possible differences are not yet well defined.
      The case we report suggests that the Cutting Balloon achieves a better final
      result than conventional PTCA, by making the tissue more amenable to being pushed
      outward through the stent struts.

PMID- 10931622
TI  - Successful sealing of perforation of saphenous vein graft by coronary stent.
AB  - Coronary artery perforation is a rare occurrence during angioplasty and could
      lead to major complications requiring emergency surgical intervention. We
      describe a case of perforation of a saphenous vein graft during stenting. The
      perforation was successfully sealed by a second coronary stent.

PMID- 10931623
TI  - Transseptal puncture guided by intracardiac echocardiography during percutaneous
      transvenous mitral commissurotomy in patients with distorted anatomy of the fossa
      ovalis.
AB  - Positioning of the transseptal needle during percutaneous transvenous mitral
      commissurotomy (PTMV) can become a difficult and risky procedure when distortion
      of the interatrial septum exists. We present two cases where intracardiac
      echocardiography (ICE) facilitated the transseptal puncture in the presence of
      bulging of the fossa ovalis into the right atrium.

PMID- 10931624
TI  - Acute left anterior descending artery occlusion in a hemophiliac A patient during
      recombinant factor VIII infusion: treatment with coronary angioplasty.
AB  - Acute myocardial infarction in association with the replacement of recombinant
      factor VIII in hemophiliacs has not been documented. We describe the use of PTCA
      in a hemophiliac A patient who developed acute myocardial infarction during
      factor VIII replacement. Because surgery in hemophiliac A patients remains
      hazardous, PTCA seems to be an attractive alternative.

PMID- 10931625
TI  - Physiology of critical pulmonary valve obstruction in the neonate.

PMID- 10931626
TI  - Cutting balloon angioplasty for in-stent restenosis.

PMID- 10931627
TI  - Balloon aortic valvuloplasty revisited: the role of the inoue balloon and
      transseptal antegrade approach.
AB  - Percutaneous aortic balloon valvuloplasty (PABV) was developed to provide a less
      invasive alternative to aortic valve replacement. Despite initially favorable
      results, PABV has not produced reliable and durable outcomes. The Inoue balloon
      used for PABV via an antegrade transseptal approach may offer an improvement over
      the Mansfield balloons via the identical route. Thirteen consecutive patients
      with severe symptomatic aortic stenosis were referred for percutaneous aortic
      balloon valvuloplasty. All patients were considered unacceptably high-risk
      surgical candidates. Seven consecutive patients underwent antegrade transseptal
      PABV with Mansfield balloons and in the following six the Inoue balloon was used.
      The study group was characterized by advanced age (mean, 77) and multiple
      comorbid conditions (mean, 2.5/patient). Before PABV, the two groups did not
      differ with respect to age, mean NYHA class, LVEF, transaortic gradient, cardiac
      output, or aortic valve area. All patients had initial hemodynamic improvement.
      Complications included one stroke and one vascular injury. After valvuloplasty,
      cardiac output was not significantly changed. However, there was a significant
      decrease in aortic gradient and an increase in aortic valve area in both groups;
      the increase in aortic valve area was significantly greater in those treated with
      the Inoue balloon (P = 0. 039). Total follow-up mortality was high but appeared
      to be delayed in the Inoue group. The use of the Inoue balloon with an antegrade
      transseptal approach warrants further investigation as a preferred technique for
      PABV.

PMID- 10931628
TI  - Transseptal antegrade access for aortic valvuloplasty.

PMID- 10931629
TI  - Vasoseal after intra-aortic balloon pump removal: a pilot study.
AB  - Vascular complications after removal of an intra-aortic balloon pump (IABP) have
      been reported to occur in up to 15% of patients. Vasoseal, a vascular hemostasis
      device (VHD), has been shown to be safe and effective in rapidly achieving
      hemostasis after a cardiac catheterization or percutaneous coronary intervention.
      We propose that similar results can be obtained with the VHD when removing an
      IABP. However, it is necessary to first gain first the experience of deploying
      the VHD without insertion of a guidewire. We studied 10 patients in whom Vasoseal
      was utilized after an IABP was removed. The primary endpoint was a composite of
      major or minor bleeding, infection, and any vascular complication at 7 days. The
      time to achieve hemostasis was also assessed. There was not a single episode of
      bleeding, infection, or vascular injury at 7 days. The time to hemostasis ranged
      between 8 and 17 min (mean, 12.9 min). This VHD can be utilized safely and
      efficaciously when removing an IABP.

PMID- 10931630
TI  - The use of intrastent peripheral stent in large coronary arteries: report of
      three cases.
AB  - We report three cases of coronary angioplasty using the IntraTherapeutics
      Intrastent biliary stent. We describe a technique utilizing routine coronary
      angioplasty equipment including 8 Fr guiding catheters and 0.014" guidewires.
      This technique can be easily performed in large-diameter coronary arteries.

PMID- 10931631
TI  - Transcatheter closure of membranous ventricular septal defects with a new nitinol
      prosthesis in a natural swine model.
AB  - Transcatheter closure of a membranous ventricular septal defect (MVSD) is much
      more difficult than closure of other intracardiac defects because of the
      proximity to the aortic and tricuspid valves and their relatively large size in
      small children. In this report, transcatheter closure of naturally occurring
      membranous VSDs was attempted in 12 Yucatan minipigs. The prosthesis is
      constructed from fine Nitinol wires in the shape of two buttons and a connecting
      waist filled with polyester fiber. Two kinds of prosthesis were used in this
      study: concentric and eccentric left-sided retention disks. A 6 or 7 Fr delivery
      sheath was advanced across the membranous VSD over a wire from femoral vein. The
      prosthesis was inserted through the sheath by pushing the delivery cable to
      deploy a button into left ventricle and the second button was then deployed into
      right ventricle by withdrawing the sheath. Successful implantation of the device
      was achieved in all animals except one. Complete closure rate was 58.3%
      immediately after placement, 100% at 1 week, 90.9% at 1 month and 3 months, and
      100% at 6 months. An associated aneurysm of the membranous septum increased
      significantly in size in two of three animals using the concentric device, and in
      none of the animals using the eccentric device. A trace to mild aortic
      regurgitation was present in two of the three animals using the concentric
      device, and only in one of the eight animals using the eccentric device. Five
      animals developed a trace to mild tricuspid regurgitation. Pathologic examination
      showed all devices to be covered by smooth neoendothelium at 3 months. This
      report presents the first experimental study where closure of membranous
      ventricular septal defects in a swine model was attempted by specially
      constructed devices. Procedural success and occlusion rates are very encouraging
      but overall results cannot equal surgery. Further experimentation is needed with
      devices that are redesigned according to the experience gained from this study.

PMID- 10931632
TI  - Air embolism in the right coronary artery occurring during the left coronary
      angioplasty using the guiding catheter with a side hole.

PMID- 10931633
TI  - Reply to the letter to the editor by janin:

PMID- 10931634
TI  - Optimal stent positioning in coronary arteries: partial balloon inflation to
      overcome cardiac cycle-related motion of the stent/delivery system.

PMID- 10931635
TI  - Effect of an auditory stress on peritoneal and alveolar cells in C57 BL/6J mice
      of advanced age.
AB  - The aim of this study was to analyse the effects of auditory stress on peritoneal
      and alveolar macrophages in C57 BL/6J mice of advanced age, and to compare the
      results to those obtained in old mice submitted to a sham stress, and to those
      observed in young mice submitted to the same auditory stress. We used a
      chemiluminescence assay to measure the production of free oxygen radicals (FOR)
      by macrophages. Eight 22 month-old mice were exposed to a sound stress of 110 dB
      for three consecutive nights; nine were submitted to a sham stress. The results
      were compared to those obtained in young (8 week-old) mice, 21 submitted to noise
      stress, and 17 controls. The corticosterone level was not increased after stress
      in any group. FOR production in old mice was significantly higher than that in
      young mice. Stress did not induce significant changes in FOR production by
      alveolar cells in young mice; however, the FOR production by alveolar cells was
      significantly higher in the stressed group than in the control group of old mice.
      These results show that noise stress is associated with modifications of
      macrophage functions that are influenced by cell localization, the behaviour of
      alveolar and peritoneal macrophages of old mice being clearly different in our
      experimental model.

PMID- 10931636
TI  - Stable and versatile active acridinium esters I.
AB  - The synthesis of acridinium esters with a linking group directly attached to the
      acridine nucleus is described. This strategy will allow the widest possible
      choice of variously substituted phenyl esters without restricting them to those
      structures bearing linking groups on the phenol.

PMID- 10931637
TI  - Stable and versatile active acridinium esters II.
AB  - The synthesis of acridinium esters with a linking group directly attached to the
      acridine nucleus is described. This strategy will allow the widest possible
      choice of variously substituted phenyl esters without restricting them to those
      structures bearing linking groups on the phenol.

PMID- 10931639
TI  - Effect of homocysteine on polymorphonuclear leukocyte activity and luminol
      dependent chemiluminescence.
AB  - Homocysteine is a non-protein-forming sulphur amino acid that plays an important
      role in remethylation and trans-sulphuration processes. In recent years, a high
      plasma homocysteine concentration has been implied as a possible
      pathophysiological factor in atherosclerosis and artery and deep vein thrombosis,
      probably through generation of H(2)O(2), enhanced platelet activity and increased
      production of macrophage-derived tissue factor. Furthermore, an increase of
      polymorphonuclear leukocyte (PMN) activity mediated by homocysteine-generated
      H(2)O(2) has also been reported. Because some preliminary experimental results in
      our laboratory did not confirm this effect of homocysteine on PMNs, we
      investigated the effect of homocysteine on the activity of PMNs, measured by
      their luminol-dependent chemiluminescence. Moreover, we also studied the effect
      of homocysteine in a luminol-hypochlorite chemiluminescent system. Our results
      clearly indicate that homocysteine at micromol/L concentrations (10-100
      micromol/L) slightly inhibits neutrophil chemiluminescence, while it strongly
      inhibits the luminescence of the luminol-hypochlorite system. Therefore, the
      hypothesis that homocysteine induces an increase of H(2)O(2)-mediated neutrophil
      activity is not supported and, probably, the common opinion that views the
      H(2)O(2) generated by homocysteine as a possible mechanism for cardiovascular
      damage should be reconsidered.

PMID- 10931638
TI  - Chemiluminescence activity in whole blood phagocytes of dogs naturally infected
      with Leishmania infantum.
AB  - Dogs are the domestic reservoir of Leishmania infantum, a vector-borne
      intracellular protozoan agent of human visceral leishmaniasis. The role of
      polymorphonuclear leukocytes (PMNs) in the immune defence against this parasite
      has been poorly studied. We have investigated the function of peripheral blood
      PMNs in naive beagle dogs that have been naturally exposed to phlebotomine
      vectors in an area highly endemic for canine leishmaniasis, and found infected by
      Leishmania at the end of the transmission season. Whole blood phagocyte oxidative
      metabolism was assessed by a rapid method that determines a luminol-amplified
      chemiluminescence (CL) emission. This was evaluated using either a soluble
      stimulant, phorbol mirystate acetate (PMA), or phagocytic stimuli, such as
      zymosan unopsonized (ZYM) or opsonized with autologous serum (OPZ). In blood
      samples taken 2 months after exposure to Leishmania transmission, data on CL
      emission revealed a significant decrease of reactive oxygen intermediates (ROI)
      production in the presence of both PMA and ZYM, compared with blood samples
      obtained from dogs before exposure. On the contrary, no variations in CL emission
      were detected in presence of OPZ. Our data indicate that immunological changes
      occur early in canine leishmaniasis and confirm that the role of PMNs and their
      products need to be clarified.

PMID- 10931641
TI  - 5th International symposium on hormones and bioactive substances in milk:
      highlights.
AB  - The 5th International Symposium on Hormones and Bioactive Substances in Milk took
      place in Smolenice Castle near Bratislava, Slovakia on October 7-12, 1996.
      Current knowledge, opinions and perspectives of various aspects were presented
      and thoroughly discussed at the meeting by the representatives of science and
      industry from 17 countries. A significant progress in the expanding field was
      again noted and recent development in specific areas as reviewed in six
      scientific sessions has been summarized by organizers. We are also pleased to
      announce that as the result of unanimous decision of the International Organizing
      Committee the 6th International Symposium on Hormones in Milk will be held in
      1999 again in Smolenice Castle.

PMID- 10931640
TI  - Synthesis and characterization of two novel [Ru(bpy)(2)(phen)](2+)-based
      electrochemiluminescent labels.
AB  - Two novel electrochemiluminescent labels, bis(2, 2'-bipyridine)[5-(3-carboxylic
      acid-propionamido)-1, 10-phenanthroline]ruthenium(II) hexafluorophosphate
      dihydrate and bis(2,2'-bipyridine)[5-(4-carboxylic acid-butanamido)-1, 10
      phenanthroline]ruthenium(II) hexafluorophosphate dihydrate, were synthesized and
      confirmed by IRelemental analysis, and (1)H-NMR spectra were completely assigned
      using the (1)H-(1)H COSY technique. Cyclic voltammograms with different scan
      rates showed quasi-reversible electrochemical behaviour of the two Ru (II)
      complex labels in MeCN solution. Electronic absorption, photoluminescence and
      electrochemiluminescence of Ru(II) complexes were also characterized.

PMID- 10931642
TI  - Effects of reduced milk intake on lymphocytes of neonatal rats.
AB  - Prolactin (PRL) is an immunoregulatory molecule. We previously reported that milk
      PRL passes to the circulation of the neonatal rat and plays a role in neonatal
      immune system maturation. Neonatal rats that had ingested PRL-poor milk
      (bromocriptine treatment of the dam) from days 2-5 of life, showed changed
      patterns of immune system development. In order to rule out the possibility that
      these changes were due to reduced milk intake rather than to milk-PRL, in this
      current study we varied neonatal milk intake by adjusting litter size to 6 or 12
      pups. At day 10, splenocytes and thymocytes were: 1. tested for in vitro
      proliferation to the mitogens phytohemagglutinin or to concanavalin A; 2. stained
      with monoclonal antibodies to surface differentiation antigens and analyzed by
      flow cytometry. We found that reduced milk intake (litter size of 12) led to
      decreased mitogen responsiveness, the opposite of what was seen after ingestion
      of PRL-poor milk. However, a reduction in milk had no significant affect on
      expression of surface differentiation antigens. Therefore, the changes in
      neonatal immune development following ingestion of PRL-poor milk cannot be
      attributed to a decrease in total milk volume.

PMID- 10931643
TI  - Organ distribution of iodide transporter (symporter) in the rat:
      immunohistochemical study.
AB  - Iodide transporter/symporter (NIS) was identified immunohistochemically in rat
      tissues using specific antipeptide serum. Anti-NIS serum was raised in New
      Zealand white rabbits immunized with a conjugate of synthetic NIS peptide (39-53)
      with bovine serum albumin. Immunohistochemical analysis was performed by avidine
      biotin complex method. NIS immunoreactivity was visualized in the thyroid gland,
      gastric and small intestine mucosa, anterior pituitary, adrenal medulla,
      pancreatic islets, kidney, chorioid plexus and several brain and spinal cord
      nuclei. When using antiserum preincubated with synthetic NIS peptide (39-53) or
      rat thyroid homogenate containing NIS, no significant stain of the thyroid gland
      was detected. These findings suggest that NIS is widely distributed and that the
      method used is suitable for studying the distribution of NIS in rats.

PMID- 10931644
TI  - Involvement of Catecholestrogens in the release of pituitary hormones.
AB  - Catecholestrogens (CE), natural metabolic products of 17beta-estradiol and
      estrone, were assayed in anterior and posterior pituitary lobes and in the median
      eminence of the rat. The highest CE values were found in the median eminence and
      the lowest in the anterior pituitary. The CE concentrations in pars nervosa and
      pars intermedia of the posterior pituitary were quite similar. No sexual
      difference in the CE content was found in median eminence, anterior and posterior
      pituitary lobes. The highest CE concentrations were found in the median eminence
      and pars intermedia of lactating rats. During the estrous cycle median eminence
      CE showed maximal values in the morning of the proestrus, while anterior
      pituitary CE showed a decrease in the afternoon of the proestrus. Posterior
      pituitary lobe CE content did not change throughout the stages of the estrous
      cycle. Ovariectomy decreased CE content in the anterior pituitary but did not
      change the CE content in pars nervosa and pars intermedia of the posterior
      pituitary lobe. Estrogen therapy in ovariectomized animals increased CE content
      in pars nervosa. In the lactating rats, the separation of mothers from their pups
      for 4 h increased CE content in the posterior lobe and showed no variations in
      the anterior lobe. When pups were replaced and allowed to suckle for 5 and 30
      min, CE content decreased in both the anterior and posterior pituitary lobes.
      Pars nervosa CE varied with suckling in the same way as the whole posterior lobe
      did. Pars intermedia and median eminence, both of which exhibited high CE values
      in the lactating rats, showed no CE variations in the model of
      separation/suckling. Parallel studies of COMT activity showed no variations in
      any model and in any pituitary lobe except anterior pituitary during the estrous
      cycle: COMT activity at Diestrus 2 was significantly low. The results obtained
      suggest that the CE are involved in the hormonal changes taking place in rat
      sexual cycle and lactation.

PMID- 10931645
TI  - Steroid secretion of preovulatory rat ovarian follicles in the presence of other
      steroids and aromatase inhibitor CGS 16949A.
AB  - Female Wistar rats, displaying a regular 4-day oestrus cycle, were killed in
      succession every 2 or 3 h on the day of pro-oestrus until ovulation. The
      population of preovulatory ovarian follicles was isolated and cultured for 24 h
      in Eagle's medium or in this medium supplemented with testosterone, or
      progesterone or aromatase inhibitor (CGS 16949A, Ciba-Geigy). In collected media
      the released steroids were estimated. The follicles isolated in the morning and
      afternoon secreted predominantly oestradiol and androgens. In the evening a fall
      in oestradiol and androgen levels was observed, whereas progesterone production
      rose, reaching a peak value at 20.00 h. Addition of progesterone suppressed
      oestradiol release at 18.00 h. CGS 16949A inhibited oestradiol secretion in all
      the cultures investigated and in some of them also affected progesterone
      secretion. The presence of testosterone in control cultures changed the
      progesterone release and stimulated oestradiol production at 20.00 h and 22.00 h,
      i.e. during oestradiol decline. These results suggest that the fall in oestradiol
      production is initiated by the lack of aromatizable androgens and this is
      followed by a suppression of aromatase activity. The role of progesterone as an
      inhibitor of the aromatase enzyme system is very probable.

PMID- 10931646
TI  - Hydrochlorothiazide prevents bone loss in castrated male mice.
AB  - The castration of male mice results in osteopenia which is a suitable model for
      evaluating the effect of thiazides on bone. The bones of castrated mice were
      characterized by a decrease of ash weight, bone density and calcium and phosphate
      bone content. When such castrated mice were treated with high dose of
      hydrochlorothiazide (2 mg/day/mouse) the changes in bone density and bone mineral
      concentration resulting from the castration were prevented. Our data indicate a
      beneficial effect of long-term thiazide administration on bone mineral content in
      male mice, which is dose dependent.

PMID- 10931647
TI  - Progesterone, androgen and estradiol production by porcine luteal cell
      subpopulations: dependence on cell composition and periods of luteal phase.
AB  - The size and number small (Sc) and large (Lc) luteal cells and the steroids they
      secrete were determined in porcine corpora lutea (CL) collected on days 1-3, 8-10
      and 14-16 of the estrus cycle. The cells were separated with the aid of Ficoll
      linear gradient. The size of Sc increased in middle-luteal phase (MLP) in
      comparison with early luteal phase (ELP) and retained consistent value until the
      end of the luteal phase (LLP). Lc increased in size with advancing luteal phase,
      their number per CL being greater in MLP than in ELP but decreased in LLP. In
      contrast, the number of Sc decreased in MLP in comparison with ELP and did not
      change in LLP. At the initial luteal phase the majority of small cells did not
      show any histochemical reactivity for delta5-3beta-hydroxysteroid dehydrogenase
      which then increased with luteal phase progress. Lc collected during ELP showed
      5.7 times higher androgen secretion than Sc. A decrease of androgen secretion by
      Lc was observed as the luteal phase progressed but it was three times higher in
      Sc than in Lc collected during LLP. Both types of luteal cells produced estradiol
      even without the addition of substrates. Endogenous estradiol content was always
      higher in Lc than in Sc. Moreover, estradiol secretion by both cell types was
      higher in LLP than in MLP and ELP. These findings suggest that the view on
      granulosa origin of Lc and theca origin of Sc as raised by others may be
      oversimplified. In appears that Sc most likely undergo hypertrophy, but retain
      their prior phenotype and also that some Lc gradually dedifferentiate to Sc as
      the corpus luteum ages.

PMID- 10931648
TI  - Diurnal rhythm of serum melatonin, ACTH and cortisol in asthma patients with long
      term glucocorticoid treatment.
AB  - Forty one patients (21 women and 20 men aged 35 to 45 years), with bronchial
      asthma were divided into two groups: those treated with glucocorticoids (with an
      equivalent daily dose of 8 mg prednisone) and those receiving no glucocorticoid
      preparations. The control group consisted of 27 healthy volunteers. The diurnal
      rhythm of serum melatonin, ACTH and cortisol was evaluated in all subjects. It
      was found that the dysfunction and reduced reactivity of the pituitary-adrenal
      axis in asthmatics receiving chronic glucocorticotherapy was accompanied by
      suppressed melatonin rhythm.

PMID- 10931649
TI  - Assessment of the relationship between collagen metabolism and selected hormonal
      factors in extremely obese women before and after jejunoileostomy.
AB  - The majority of obese persons have hyperinsulinemia and disturbances in the
      secretion of melatonin, catecholamines and pituitary, thyroid, adrenal and
      gonadal hormones. These hormones play an important role in the regulation of
      collagen metabolism either by acting directly or by influencing IGF-I production.
      This study aimed at ascertaining whether, and to what degree, the changes in the
      concentration of hormones listed above as well as in the concentration of sex
      hormone-binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) affect
      the metabolism of collagen as evaluated indirectly from the measurement of
      propeptides of type I (PICP) and type III procollagen (PIIINP) in blood serum and
      hydroxyproline in urine. The study compared 30 women with extreme obesity before
      and three to five years after jejunoileostomy with 20 healthy women of
      reproductive age. All non-operated obese women showed significantly increased
      concentration of serum insulin, IGF-I, melatonin, norepinephrine, free
      triiodothyronine, estradiol, total and free testosterone, PICP, PIIINP and
      urinary excretion of hydroxyproline, while the levels of epinephrine,
      progesterone and SHBG were significantly decreased. Changes in the level of the
      examined markers of collagen metabolism correlated positively with the
      concentration of insulin, IGF-I and sex hormones, while the correlation with
      epinephrine, cortisol and thyroid hormones was negative. All women who were
      treated previously by jejunoileostomy showed a decreased of body mass to regular
      values, normalization of hormonal disturbances and normal collagen metabolism.
      The obtained results show that the increased collagen metabolism observed in
      extremely obese women is caused indirectly by altered endocrine activity.

PMID- 10931650
TI  - Building relationships between academia and the pharmaceutical industry.
AB  - 'The climate is perfect for a proactive search for partners between industry and
      academia.'

PMID- 10931651
TI  - Novel drug development strategy targets protein 'export'

PMID- 10931652
TI  - A new target for HIV-1 entry inhibition?

PMID- 10931653
TI  - Signalling in Huntington's disease: novel targets identified.

PMID- 10931655
TI  - Virtual drug resistance testing in HIV.

PMID- 10931654
TI  - Gender-specific responses reveal untapped potential of kappa-opioids.

PMID- 10931657
TI  - Identification and in vivo efficacy of small-molecule antagonists of integrin
      alphavbeta3 (the vitronectin receptor).
AB  - The integrin alphavbeta3 is thought to play a key role in the initiation and/or
      progression of several human diseases, including osteoporosis, restenosis
      following percutaneous transluminal coronary angioplasty (PTCA), rheumatoid
      arthritis, cancer and ocular diseases. Antagonism of integrin alphavbeta3 is
      therefore expected to provide an approach for the treatment and/or prevention of
      these diseases. A variety of potent, small-molecule alphavbeta3 antagonists have
      been identified, several of which are active in disease models, thereby
      demonstrating the therapeutic potential of alphavbeta3 antagonism. This review
      will focus on recent advances in the identification of small-molecule alphavbeta3
      antagonists, with an emphasis on those studies where small-molecule alphavbeta3
      antagonists have been used in proof-of-concept studies in vivo.

PMID- 10931658
TI  - ADME/PK as part of a rational approach to drug discovery.
AB  - Rational drug discovery requires an early appraisal of all factors impacting on
      the likely success of a drug candidate in the subsequent preclinical, clinical
      and commercial phases of drug development. The study of absorption, distribution,
      metabolism, excretion and pharmacokinetics (ADME/PK) has developed into a
      relatively mature discipline in drug discovery through the application of well
      established in vitro and in vivo methodologies. The availability of improved
      analytical and automation technologies has dramatically increased our ability to
      dissect out the fundamentals of ADME/PK through the development of increasingly
      powerful in silico methods. This is fuelling a shift away from the traditional,
      empirical nature of ADME/PK towards a more rational, in cerebro approach to drug
      design.

PMID- 10931659
TI  - Serial analysis of gene expression: from gene discovery to target identification.
AB  - Serial Analysis of Gene Expression (SAGE) is a sequence-based genomics tool that
      features comprehensive gene discovery and quantitative gene expression
      capabilities. As an 'open' system, SAGE can reveal which genes are expressed and
      their level of expression rather than merely quantifying the expression level of
      a predetermined, and presently incomplete, set of genes as carried out by
      'closed' system gene expression profiling platforms such as microarrays. These
      distinguishing attributes enable SAGE to be used as a primary discovery engine
      that can characterize human disease at the molecular level while illuminating
      potential targets and markers for therapeutic and diagnostic development,
      respectively.

PMID- 10931661
TI  - PharmacogenomicsQualitative gene profiling using differential analysis of
      transcripts with alternative splicing.

PMID- 10931660
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- 10931662
TI  - Combinatorial chemistryMatrix metalloprotease inhibitors.

PMID- 10931664
TI  - The exquisite corpse: a shifting view of the shifting balance.

PMID- 10931663
TI  - Contribution of NO/ONOO- pathway to the deleterious effect of traumatic brain
      injury in mice.

PMID- 10931665
TI  - The armpit effect in hamster kin recognition.

PMID- 10931666
TI  - Selfish cells threaten multicellular life.

PMID- 10931668
TI  - The evolution of base composition and phylogenetic inference.
AB  - Base composition varies at all levels of the phylogenetic hierarchy and
      throughout the genome, and can be caused by active selection or passive mutation
      pressure. This variation can make reconstructing trees difficult. However, recent
      tree-based analyses have shed light on the forces responsible for the evolution
      of base composition, forces that might be very general. More explicit tree-based
      work is encouraged.

PMID- 10931667
TI  - Mites and birds: diversity, parasitism and coevolution.
AB  - Ectoparasites play important roles in the lives of birds. Among these parasites,
      mites offer unique potential because of their extraordinary ecological and
      evolutionary diversity. However, the basic biology of most mites is poorly
      understood, and misleading extrapolations are sometimes made from better studied
      systems involving lice and fleas. Most importantly, not all bird-associated mites
      are parasitic; indeed, recent research suggests that some might even be
      beneficial. Here, we summarize what is known about the diversity of bird-mite
      relationships, and highlight how mites provide an ideal tool for the study of
      host life histories, sexual selection, immunocompetence and cospeciation.

PMID- 10931669
TI  - Arbuscular mycorrhizal fungi, Collembola and plant growth.
AB  - Arbuscular mycorrhizal fungi are ubiquitous in field soils, as are mycophagous
      animals such as Collembola. It has been suggested that these animals reduce the
      functioning of the mycorrhiza and are thus detrimental to plant growth. However,
      recent choice experiments suggest that Collembola preferentially feed on
      nonmycorrhizal fungi in the rhizosphere. If these preferences also occur in field
      soils, then Collembola might indirectly benefit plants through an enhancement of
      mycorrhizal functioning and indirect multitrophic links to foliar-feeding insect
      herbivores.

PMID- 10931670
TI  - Edge effects and ecological processes: are they on the same scale?

PMID- 10931671
TI  - Reply from W.F. Laurance.

PMID- 10931672
TI  - Costs and benefits of Web access to museum data.

PMID- 10931673
TI  - Costs and benefits of Web access to museum data.

PMID- 10931675
TI  - Reply from M. de L. Brooke.

PMID- 10931674
TI  - Costs and benefits of Web access to museum data.

PMID- 10931676
TI  - Have we forgotten the forest because of the trees?

PMID- 10931678
TI  - Microsatellite frequencies in different taxa.

PMID- 10931677
TI  - Reply from N. Brokaw and R.T. Busing.

PMID- 10931679
TI  - Reply from P. Sunnucks.

PMID- 10931681
TI  - Tinker, tailor, scientist, advocate!

PMID- 10931680
TI  - Resistance to xenobiotics and parasites: can we count the cost?
AB  - The nature and cost of single genes of major effect is one of the longest running
      controversies in biology. Resistance, whether to xenobiotics or to parasites, is
      often paraded as an obvious example of a single gene effect that must carry an
      associated fitness 'cost'. However, a review of the xenobiotic resistance
      literature shows that empirical evidence for this hypothesis is, in fact, scarce.
      We postulate that such fitness costs can only be fully interpreted in the light
      of the molecular mutations that might underlie them. We also derive a theoretical
      framework both to encompass our current understanding of xenobiotic resistance
      and to begin to dissect the probable cost of parasite resistance.

PMID- 10931682
TI  - Farnesyltransferase inhibitors potentiate the antitumor effect of radiation on a
      human tumor xenograft expressing activated HRAS.
AB  - Successful radiosensitization requires that tumor cells become more
      radiosensitive without causing an equivalent reduction in the survival of cells
      of the surrounding normal tissues. Since tumor cell radiosensitivity can be
      influenced by RAS oncogene activation, we have hypothesized that inhibition of
      oncogenic RAS activity would lead to radiosensitization of tumors with activated
      RAS. We previously showed in tissue culture that prenyltransferase treatment of
      cells with activated RAS resulted in radiosensitization, whereas treatment of
      cells with wild-type RAS had no effect on radiation survival. Here we ask whether
      the findings obtained in vitro have applicability in vivo. We found that
      treatment of nude mice bearing T24 tumor cell xenografts with farnesyltransferase
      inhibitors resulted in a significant and synergistic reduction in tumor cell
      survival after irradiation. The regrowth of T24 tumors expressing activated RAS
      was also significantly prolonged by the addition of treatment with
      farnesyltransferase inhibitors compared to the regrowth after irradiation alone.
      In contrast, there was no effect on the radiosensitivity of HT-29 tumors
      expressing wild-type RAS. These results demonstrate that specific
      radiosensitization of tumors expressing activated RAS oncogenes can be obtained
      in vivo.

PMID- 10931683
TI  - Influence of ATM function on interactions between telomeres and nuclear matrix.
AB  - The ATM (ataxia telangiectasia mutated) gene product has been implicated in
      mitogenic signal transduction, chromosome condensation, meiotic recombination,
      and cell cycle control. The human ATM protein shows similarity to several yeast
      and mammalian proteins involved in meiotic recombination and cell cycle
      progression. Because of the homology of the human ATM gene to the TEL1 and rad3
      genes of yeast, it has been suggested that mutations in ATM could lead to
      defective telomere maintenance. Recently, we have shown that the ATM gene
      product, which is defective in the cancer-prone disorder ataxia telangiectasia
      (AT), influences chromosome end associations and telomere length. A possible
      hypothesis explaining these results is that the defective telomere metabolism in
      AT cells is due to altered interactions between the telomeres and the nuclear
      matrix. These interactions were examined in nuclear matrix halos prior to and
      after irradiation. A difference was observed in the ratio of soluble and matrix
      associated telomeric DNA between cells derived from AT and normal individuals.
      Treatment with ionizing radiation affected the ratio of soluble and matrix
      associated telomeric DNA only in the AT cells. To test the hypothesis that the
      ATM gene product is involved in interactions between telomeres and the nuclear
      matrix, such interactions were examined in human cells expressing either a
      dominant-negative effect or complementation of the ATM gene. The phenotype of RKO
      colorectal tumor cells expressing ATM fragments containing a leucine zipper motif
      mimics the altered interactions of telomere and nuclear matrix seen in AT cells.
      Fibroblasts from AT individuals transfected with a wild-type ATM gene had
      corrected telomere-nuclear matrix interactions. In experiments designed to
      determine whether there is a link between the altered telomere-nuclear matrix
      interactions and defective telomere movement and clustering, a significant
      difference was observed in the ratio of soluble compared to matrix-associated
      telomeric DNA sequences in meiocytes of Atm(-/-) and control mice. These results
      suggest that the ATM gene influences the interactions between telomeres and the
      nuclear matrix and that alterations in telomere chromatin could be at least
      partly responsible for the pleiotropic phenotypes of the ATM gene. This paper
      summarizes our recent publications on the influence of inactivation of ATM on the
      interaction of telomeres with nuclear matrix in somatic and germ cells.

PMID- 10931685
TI  - Role of PRKCM (PKCmu) in radiation-induced increase of JUN proto-oncogene mRNA
      levels in B-lineage lymphoid cells.
AB  - Exposure of cells to ionizing radiation results in both activation of protein
      kinase C (PRKC, also known as PKC) and induction of transcription of the JUN
      proto-oncogene. PRKC plays a pivotal role in radiation-induced JUN expression,
      since inhibition of PRKC abrogates the JUN signal. However, the specific PRKC
      isoforms involved in radiation-induced elevation of JUN mRNA levels have not been
      identified. Here we demonstrate that in DT40 B-lineage lymphoid cells, the mu
      isoform of PRKC (PRKCM) is critical for the response of JUN to ionizing
      radiation. The zinc chelator, 1, 10-phenanthroline, abrogated induction of JUN
      after exposure to ionizing radiation, indicating that this PRKCM-mediated
      response is also dependent on zinc.

PMID- 10931684
TI  - Lack of effect of TP53 status on fluorodeoxyuridine-mediated radiosensitization.
AB  - Substantial evidence suggests that TP53 (also known as p53) status can influence
      the response of cells to chemotherapy and radiation. We wished to determine if
      TP53 function affected the response of cells to fluoropyrimidines and radiation,
      a combination used for tens of thousands of patients each year. To assess the
      role of TP53 in fluoropyrimidine-mediated radiosensitization, we carried out
      experiments using RKO parental cells (wild-type TP53) and RKO cells
      overexpressing mutant TP53 (which blocks TP53 function) or expressing E6 (which
      degrades TP53). We found that TP53 function had no effect on the ability of
      fluorodeoxyuridine to increase radiation sensitivity. These findings are
      consistent with the hypothesis that the late G(1)-phase checkpoint, which is
      mediated by TP53, is not crucial to radiosensitization. Rather, the ability of
      cells to progress in to S phase in the presence of the drug, which is independent
      of TP53, is more closely associated with increased radiation sensitivity.

PMID- 10931686
TI  - Keratinocytes exposed to ultraviolet radiation reveal three down-regulated genes
      with potential function in differentiation and cell cycle control.
AB  - The incidence of skin cancer is increasing in epidemic proportion. Although solar
      UV radiation is known to be the major risk factor, much information is lacking
      about the molecular mechanisms leading to skin cancer. To gain a deeper insight
      into these mechanisms, we have examined cells of a human keratinocyte cell line
      (HaCat) after exposure to 0.16 minimal erythema doses of UVB radiation. This dose
      led to an S-phase delay that was reversible 22 h postirradiation. To examine gene
      expression 10 h after UV irradiation, a nonradioactive differential display was
      employed. Three genes were identified as being down-regulated significantly. The
      first encodes for topoisomerase-IIbeta-binding protein 1 (expression level 5% 6 h
      after irradiation). This protein is associated with human topoisomerase IIbeta
      and appears to be necessary for DNA replication during the onset of S phase. The
      second gene product has previously been reported to be involved in
      differentiation and is therefore known as differentiation-dependent A4 protein
      (28% 8 h after irradiation). The third gene is XPO1 (also known as CRM1) (5% 8 h
      after irradiation), whose protein is involved in nuclear export of mRNA
      molecules. Differential expression of these genes after UV irradiation has not
      been reported. Because of their potential involvement in cell cycle control and
      differentiation, these proteins could be important for understanding the reaction
      of keratinocytes after exposure to UV radiation.

PMID- 10931687
TI  - Protection of human tumor cells of differing radiosensitivity by WR-1065.
AB  - We examined the ability of WR-1065, the biologically active aminothiol form of
      the clinically used drug amifostine (WR-2721, Ethyol), to protect cultures of two
      human glioblastoma cell lines of greatly differing radiosensitivity from the
      cytotoxic effects of gamma radiation. M059J cells are extremely radiosensitive
      compared to M059K cells (which were derived from the same tumor) and are
      defective in the DNA-dependent protein kinase (DNAPK)-mediated pathway for the
      repair of DSBs. In spite of their marked phenotypic differences, the two
      glioblastoma lines were protected equivalently ( approximately 1.8-fold) after a
      30-min preirradiation treatment with 4 mM WR-1065. These findings are in
      agreement with earlier studies that showed no relationship between the ability of
      another aminothiol, cysteamine, to protect human tumor cells with differing
      abilities to repair DSBs and/or radiosensitivity. Thus it appears that
      differences in intrinsic radiosensitivity and ability to repair DSBs are not
      important general factors in the modulation of the radiosensitivity of human
      cells by aminothiols. Because of a previous report that the radiosensitive mutant
      rodent xrs5 cell line (which, like M059J, is defective in the DNAPK-mediated
      pathway for repairing DSBs) is unusually refractory to the radioprotective
      effects of WR-1065, we re-examined the ability of WR-1065 to protect these cells.
      In contrast to the earlier studies, both the wild-type and mutant rodent lines
      were protected extensively by WR-1065. This discrepancy might be related to some
      unknown factor, such as differences in chromatin organization among xrs5
      subclones that arise during their karyotypic evolution, possibly leading to
      altered DNA-drug associations.

PMID- 10931688
TI  - On the efficiency of hole and electron transfer from the hydration layer to DNA:
      An EPR study of crystalline DNA X-irradiated at 4 K.
AB  - The aim of this project was to gain an improved understanding of how the
      efficiency of hole and electron transfer from the solvation layer to DNA
      decreases as a function of distance from DNA. The packing of DNA in crystals of
      known structure makes it possible to calculate the degree of DNA hydration with a
      precision that is significantly greater than that achievable for amorphous
      samples. Previous work on oligodeoxynucleotide crystals has demonstrated that the
      efficiency of free radical trapping by DNA exposed to ionizing radiation at 4 K
      is relatively insensitive to base sequence, conformation, counterion, or base
      stacking continuity. Having eliminated these confounding variables, it is now
      possible to ascertain the degree of radical transfer that occurs from ionized
      water as a function of DNA hydration (Gamma, in mol water/mol nucleotide). EPR is
      used to measure the hydroxyl radical concentration in crystals irradiated at 4 K.
      From a lack of hydroxyl radicals trapped in the inner hydration mantle, we
      determine that hole transfer to DNA is complete for water molecules located
      within 8 A. This corresponds to Gamma = 9-11 and indicates that hole transfer is
      100% (as efficient as direct ionization of DNA) for water molecules adjacent to
      DNA. Beyond approximately 8 A (Gamma > 10), hydroxyl radicals are observed; thus
      deprotonation of the water radical cation is seen to compete with hole transfer
      to DNA as soon as one water intervenes between the ionized water and DNA. The
      boundary for 0% hole transfer is projected to occur somewhere between 15 and 20
      waters per nucleotide. Electron transfer, on the other hand, is 100% efficient
      across the entire range studied, 4.2 </= Gamma </= 15.6.

PMID- 10931689
TI  - Surfactant sealing of membranes permeabilized by ionizing radiation.
AB  - Acute tissue injury and subsequent inflammation, including tissue edema and
      erythema, can be caused by sufficiently high levels of exposure to gamma
      radiation. The mechanism of this tissue injury is related to the generation of
      reactive oxygen intermediates (ROI) which chemically alter biological molecules
      and cell physiology. Cell membrane lipids are vulnerable to ROI-mediated lipid
      peroxidation that then leads to many of the acute tissue effects. We hypothesize
      that increased cell membrane permeability leading to osmotic swelling and
      vascular transudation is one of these effects. Thus we used adult postmitotic
      rhabdomyocytes in culture and microscopic fluorescence techniques to quantify
      radiation-induced changes in cell membrane permeability. Based on time-resolved
      dye flux measurements, a characteristic lag time of 34 +/- 3 min was determined
      between exposure to 160 Gy of gamma radiation and the decrease in membrane
      permeability. Administration of 0.1 mM nonionic surfactant Poloxamer 188 added to
      the cell medium after irradiation completely inhibited the dye loss over the time
      course of 2 h. Thus a reproducible model was developed for studying the mechanism
      of acute radiation injury and the efficacy of membrane-sealing agents. As only
      supportive measures now exist for treating the acute, nonlethal injuries from
      high-dose radiation exposure, agents that can restore cell membrane function
      after radiation damage may offer an important tool for therapy.

PMID- 10931690
TI  - Radiation-related cancer risks at low doses among atomic bomb survivors.
AB  - To clarify the information in the Radiation Effects Research Foundation data
      regarding cancer risks of low radiation doses, we focus on survivors with doses
      less than 0.5 Sv. For reasons indicated, we also restrict attention mainly to
      survivors within 3, 000 m of the hypocenter of the bombs. Analysis is of solid
      cancer incidence from 1958-1994, involving 7,000 cancer cases among 50,000
      survivors in that dose and distance range. The results provide useful risk
      estimates for doses as low as 0.05-0.1 Sv, which are not overestimated by linear
      risk estimates computed from the wider dose ranges 0-2 Sv or 0-4 Sv. There is a
      statistically significant risk in the range 0-0.1 Sv, and an upper confidence
      limit on any possible threshold is computed as 0.06 Sv. It is indicated that
      modification of the neutron dose estimates currently under consideration would
      not markedly change the conclusions.

PMID- 10931691
TI  - Functional changes in the rat distal colon after whole-body irradiation: dose
      response and temporal relationships.
AB  - The aim of this study was to determine the acute radiation response of the rat
      distal colon by in vivo and in vitro measurements of the functions of the colon
      over a range of radiation doses. Rats received a whole-body irradiation of 2 to
      12 Gy and were studied from 1 to 7 days after exposure. In vivo water and
      electrolyte absorption was measured by insertion of an agarose cylinder in the
      colon of anesthetized rats. In vitro transepithelial electrical parameters
      (potential difference, short-circuit current, transepithelial conductance) were
      measured in Ussing chambers in basal and agonist-stimulated conditions. In vivo
      and in vitro functional studies were completed by standard histological analyses.
      The majority of functional modifications appeared at 4 days after exposure. At
      this time, a dose-dependent decrease in absorption of water and sodium/chloride
      ions in the colon was noted. In contrast, a twofold increase in potassium
      secretion was observed for every radiation dose studied. The response to
      secretagogues was attenuated at doses >8 Gy. Modifications of basal
      transepithelial electrical parameters together with marked histological
      alterations were observed at 4 days with the higher doses (>/=10 Gy). In
      conclusion, these results show that functions of the colon are affected by
      irradiation and may contribute to diarrhea induced by ionizing radiation.

PMID- 10931692
TI  - Local 42 degrees C hyperthermia improves vascular conductance of the R3230Ac rat
      mammary adenocarcinoma during sodium nitroprusside infusion.
AB  - The effect of sodium nitroprusside-induced hypotension on the perfusion of the
      R3230 adenocarcinoma during local 42 degrees C hyperthermia was studied using a
      combination of intravital microscopy and laser Doppler flowmetry. Fischer 344
      rats were implanted with dorsal skin flap window chambers containing the R3230Ac
      tumor and allocated to three treatment groups (34 degrees C with nitroprusside,
      42 degrees C with nitroprusside, and 42 degrees C with 0.9% saline). After
      baseline observation at 34 degrees C, tumors were locally heated to 42 degrees C
      using a water bath and either 0.9% saline or nitroprusside sufficient to reduce
      blood pressure 20% below pretreatment baseline was infused. Nitroprusside at 34
      degrees C decreased tumor vascular conductance 40% with no effect on the diameter
      of arterioles entering the tumor. The diameter of arterioles entering 42 degrees
      C heated tumors increased 35% independent of blood pressure change. Saline at 42
      degrees C had no effect on tumor vascular conductance; however, nitroprusside at
      42 degrees C increased tumor vascular conductance 55%. Local 42 degrees C tumor
      heating, combined with a moderate reduction in blood pressure with nitroprusside,
      overrides the vascular steal effect associated with reduced perfusion pressure
      alone and results in improved tumor perfusion. Observations of the effect of
      vasodilator substances on normothermic tumor perfusion cannot be extrapolated to
      situations where moderate hyperthermia is used.

PMID- 10931693
TI  - A novel drug to reduce tumor perfusion: antitumor effect alone and with
      hyperthermia.
AB  - We have investigated the feasibility of enhancing damage induced by hyperthermia
      in SCK murine tumors by reducing tumor blood perfusion using a new agent, KB
      R8498. Within several minutes of an i.v. injection, the tumor perfusion was
      reduced to less than 20% of the control value, and it recovered to 40-70% of the
      control value by 1 h after injection. The perfusion in normal tissues decreased
      or increased soon after drug administration depending on the tissue type.
      However, by 1 h after drug treatment, perfusion in five of the seven tissues
      examined had returned to the control level. The tumor pH was also reduced after
      i.v. drug administration. Control tumors grew to four times the initial volume in
      6 days. Tumors that were heated at 42.5 degrees C for 60 min were delayed in
      growth by 4 days compared to control tumors. There was a growth delay of 14 days
      when an i.v. injection of KB-R8498 was given and the tumors were heated at 42.5
      degrees C either immediately or 1 h later. In drug-alone studies, the tumor
      growth was delayed by 4 days when the drug was infused continuously at a rate of
      30-50 mg/kg day(-1) for 7 days or about 2 days when mice were treated with five
      daily injections of 30 mg/kg KB-R8498.

PMID- 10931694
TI  - Effect of ELF magnetic fields on protein synthesis in Escherichia coli K12.
AB  - Escherichia coli K12 was used as a model system to determine whether ELF magnetic
      fields (MFs) are a general stress factor. The cells were exposed to ELF MFs (5
      100 Hz) at a maximum intensity of 14 mT r. m.s. for circularly polarized MFs and
      10 mT r.m.s. for vertically polarized MFs. The response of the cells to the MFs
      was estimated from the change in protein synthesis by using 2D PAGE.
      Approximately 1,000 proteins were separated on the 2D gels. The stress-responsive
      proteins such as CH10, DNAK, CH60, RECA, USPA, K6P1 and SODM were identified from
      the SWISS-2DPAGE database on the 2D gels. These proteins respond to most stress
      factors, including temperature change, chemical compounds, heavy metals, and
      nutrients. When the bacterial cells were exposed to each MF at 5-100 Hz under
      aerobic conditions (6.5 h) or at 50 Hz under anaerobic conditions (16 h) at the
      maximum intensity (7.8 to 14 mT r.m.s.), no reproducible changes were observed in
      the 2D gels. Changes in protein synthesis were detected by 2D PAGE with exposure
      to heat shock (50 degrees C for 30 min) or under anaerobic conditions (no
      bubbling for 16 h). Increases in the levels of synthesis of the stress proteins
      were observed in heat-shocked cells (CH60, CH10, HTPG, DNAK, HSLV, IBPA and some
      unidentified proteins) and in cells grown under anaerobic conditions (DNAK, PFLB,
      RECA, USPA and many unidentified proteins). These results suggest that 2D PAGE is
      sufficient to detect cell responses to environmental stress. The high-intensity
      ELF MFs (14 mT at power frequency) did not act as a general stress factor.

PMID- 10931731
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931695
TI  - Radioprotective action of extracellular adenosine on bone marrow cells in mice
      exposed to gamma rays as assayed by the micronucleus test.
AB  - The frequency of micronucleated polychromatic erythrocytes (PCEs) in mouse bone
      marrow was assessed after administration of dipyridamole and/or adenosine
      monophosphate (AMP) to nonirradiated mice or to mice irradiated 15 min later with
      a sublethal dose of 6.5 Gy gamma rays. In nonirradiated mice, the administration
      of the drugs increased the frequency of micronucleated PCEs significantly (by
      108%). In contrast, in irradiated mice, the number of radiation-induced
      micronucleated PCEs was significantly decreased if the mice had been pretreated
      with dipyridamole or AMP alone (by 24% after administration of each of the
      compounds) and in particular after administration of the drugs in combination (by
      36%).

PMID- 10931732
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931733
TI  - Mortality from ruptured abdominal aortic aneurysm in Wales.

PMID- 10931734
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931735
TI  - Fatal and life-threatening complications in antireflux surgery: analysis of 5502
      operations.

PMID- 10931736
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931738
TI  - CORRESPONDENCE: Author's reply

PMID- 10931737
TI  - Cost-effective carotid endarterectomy.

PMID- 10931739
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931740
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931741
TI  - CORRESPONDENCE: Authors' reply

PMID- 10931742
TI  - Intrapericardial lymphangioma with podoplanin immunohistochemical
      characterization of lymphatic endothelial cells.

PMID- 10931743
TI  - A quantitative reverse transcription and polymerase chain reaction assay for
      human IGF-II allows direct comparison of IGF-II mRNA levels in cancerous breast,
      bladder, and prostate tissues.
AB  - Previously, we showed by in situ hybridization that insulin-like growth factor
      (IGF)-II is upregulated in approximately 50% of prostate, breast, and bladder
      tumours. In this study, a quantitative competitive reverse transcription and
      polymerase chain reaction (QC RT-PCR) assay was established and used to quantify
      human IGF-II mRNA levels in cells and tissues. In this QC RT-PCR assay, a
      competitor IGF-II RNA, prepared from a newly constructed plasmid encoding the
      human IGF-II sequence with a 110-bp fragment inserted, was added to RNA samples
      prior to RT-PCR. The human IGF-II specific QC RT-PCR assay has allowed us to
      readily compare the levels of IGF-II mRNA in human tissues and cultured cells.
      Consistent with our previous observations by in situ hybridization, IGF-II mRNA
      was up-regulated in 50% of cancerous breast tissues examined as compared to the
      matching benign tissues, and IGF-II mRNA levels were higher in bladder tumours
      than breast and prostate tumours. In summary, we present here quantitative data
      confirming that a subclass of breast cancer samples has elevated levels of IGF-II
      transcripts by the new competitive RT-PCR assay.

PMID- 10931744
TI  - Endogenous IGFBP-3 is protected from inducible IGFBP-3 protease activity in
      normal adult serum.
AB  - We have recently demonstrated that the presence or absence of IGFBP-3 protease
      activity in physiological fluids may not be determined simply by the presence or
      absence of specific enzymes but rather the presence of inhibitors. In addition,
      it appears that these inhibitors may not only be associated with the protease(s)
      but with the IGFBP-3 itself, protecting it from proteolytic cleavage. To provide
      further evidence for this mechanism of regulation we investigated whether IGFBP-3
      protease activity could be unveiled in normal adult serum (NS) and whether the
      endogenous IGFBP-3 was protected from this activity. The addition of a range of
      concentrations of heparin, induced IGFBP-3 protease activity in NS. This was
      comparable to that seen in pregnancy serum (PS) by virtue of the fragmentation
      pattern and inhibitor profile. While the addition of zinc also revealed IGFBP-3
      protease activity in NS the pattern of fragments differed to that seen in PS.
      Under both conditions, however, the endogenous IGFBP-3 was not proteolytically
      modified. These results demonstrate that IGFBP-3 protease activity is present in
      NS and can be activated, although the endogenous IGFBP-3 is relatively protected
      from such activity.

PMID- 10931745
TI  - Age-related serum levels of insulin-like growth factor-I, -II and IGF-binding
      protein-3 following myocardial infarction.
AB  - Aging retards the repair process by decreasing hormone secretion from the
      somatotrophic axis, which plays a major role in tissue reconstruction after
      injury. The aim of this study was to determine the effect of aging on serum
      insulin-like growth factor-I (IGF-I), IGF-II and IGF-binding protein-3 (IGFBP-3)
      levels following myocardial infarction (MI). For four consecutive days, we
      monitored the variation of serum IGF-I, IGF-II and IGFBP-3 concentrations in 26
      patients aged 19-71 years who were diagnosed with MI. Serum IGF-I, IGF-II and
      IGFBP-3 were measured daily by double antibody radioimmunoassay. Daily serum IGF
      I concentrations showed a significant negative correlation with age (r = -0.528,
      P< 0.001). Total serum IGF-I was significantly (P = 0.002) higher in the younger
      age group (patients under 50 years) compared to the older group (50 years and
      over); 206 +/- 16 ng/ml vs 136 +/- 12 ng/ml. During this investigation, younger
      patients (under 50 years) showed no significant daily variations in IGF-I levels
      compared to older patients (50 years and over) who presented a significant
      decline (P = 0.012). Total serum IGF-II in both groups decreased significantly
      with time. Total serum IGFBP-3 in the younger age group was significantly higher
      (P = 0.046) than in the older age group (3.42 +/- 0.18 microgram/ml vs 2.95 +/-
      0.13 microgram/ml). MI patients in both groups showed significantly lower IGF-I
      and IGF-II (IGFs) with higher IGFBP-3 compared to age- and sex-adjusted levels of
      normal adults (controls). The present results confirm that age and cardiac
      condition affect IGFs and IGFBP-3 levels. We are inclined to believe that older
      patients with a cardiac condition are less able to maintain their blood IGF-I
      levels during the recovery period compared to younger patients. Given the
      biological impact of IGF-I on regeneration, this could explain why older patients
      take longer to recover and heal poorly in comparison to younger patients.

PMID- 10931746
TI  - Growth hormone treatment increases transmural colonic growth in GH-deficient
      dwarf rats.
AB  - Growth hormone (GH) has been implicated as an important factor in the growth
      regulation of several visceral organs including the gastrointestinal tract. Our
      aim was to study the effects of GH administration on colonic growth in dwarf rats
      with an isolated GH deficiency. Dwarf rats were treated with recombinant human
      growth hormone (rhGH; 2.0 mg/kg/day) for four weeks and compared with saline
      treated dwarf rats and rats with normal pituitary function. The colonic wall
      composition was measured by means of stereological techniques. RhGH treatment of
      the dwarf rats increased body weight by 80% and proximal and distal colon weight
      by 63% and 90%, when compared with placebo treated dwarf rats (P< 0.01). The
      weight of the proximal colonic mucosa increased by 83% (P< 0.01), submucosa by
      78% (P< 0.05), and the muscularis propria by 51% (P< 0.001) in rhGH treated dwarf
      rats compared with dwarf controls. The weight of the distal colonic mucosa
      increased by 88% (P< 0.01), submucosa by 88% (P< 0.05) and the muscularis propria
      by 58% (P< 0.05) compared with dwarf controls. The growth of mucosa involved all
      mucosal layers, with a 73 and 92% increase in the proximal and distal colon
      luminal surface area respectively (P< 0.001, P< 0.01). The food consumption,
      expressed as g/day/100 g BW was 13% higher in dwarf rats receiving rhGH than in
      placebo treated rats (P< 0.05) and normal control rats (P< 0.05). When weights of
      the GI tract compartments are corrected for the increase in body weight the
      effects of GH treatment were small or non-significant. RhGH administration in GH
      deficient dwarf rats induces visceral growth with a pronounced increase in
      colonic luminal surface area and growth of all layers of the colonic wall. These
      findings confirm the important role of GH in the regulation of intestinal growth.

PMID- 10931747
TI  - Bioequivalence between ready-to-use recombinant human growth hormone (rhGH) in
      liquid formulation and rhGH for reconstitution.
AB  - The bioequivalence of recombinant human growth hormone (rhGH) for reconstitution,
      at either 24 IU or 8 mg, and three strengths of liquid formulation of rhGH (5, 10
      or 15 mg per 1.5 ml, hGH) was tested in two randomized, single-blind, four
      period, crossover studies in healthy subjects. The study drugs were administered
      by subcutaneous injection at a dose of 2.5 mg rhGH/m(2)body surface area or as a
      fixed dose of 5 mg rhGH. Endogenous hGH release was suppressed by a continuous
      somatostatin infusion. The 90% confidence intervals for the estimated mean ratios
      of AUC(0-24 h)and C(max)(analysis of variance) between all products were within
      80-125% in both studies. Also, no significant differences (P> 0.05; Wilcoxon
      signed rank test) were found between t(max)for the liquid formulations of rhGH.
      These data demonstrate that there is bioequivalence between rhGH for
      reconstitution and the liquid formulations of rhGH.

PMID- 10931748
TI  - Immunofunctional vs immunoreactive growth hormone responses after resistance
      exercise in men and women.
AB  - Immunoassays for growth hormone (GH) may yield variable concentrations for the
      same sample due to the molecular heterogeneity of growth hormone and epitope
      specificity of their antibodies. Strasburger et al. developed an
      "immunofunctional" assay that only detects those GH molecules possessing intact
      sites 1 and 2, which are necessary for inducing receptor dimerization and
      subsequent signal transduction. This study compared the immunoreactive (IR) vs
      immunofunctional (IF) GH concentrations before and after acute resistance
      exercise (i.e. six sets of 10 repetition maximum squats separated by 2 min rest
      periods) in 8 men and 6 women. IF concentrations were determined by an
      ELISA(DSL)and IR GH by a monoclonal IRMA(Nichols). Both men (M) and women (W)
      demonstrated similar increases for IR (M: 1.47 vs 25.0 ng/ml; W: 4.0 vs 25.4
      ng/ml) and IF (M: 0.55 vs 11.66 ng/ml; W: 1.94 vs 10.41 ng/ml) GH following
      exercise. Post-exercise IF GH was significantly less than IR GH for both M and W.
      The ratio of IR/IF after exercise was approximately 2 and similar for both M and
      W. In summary, dynamic exercise elicited a similar rise in M and W for
      immunofunctionally active GH molecules, but the magnitude is lower than when
      detected with another conventional assay.

PMID- 10931749
TI  - Community dynamics: what happens when we rerun the tape?
AB  - The role of historical events, such as disturbances, in producing alternative
      developmental outcomes in forest structure has long been debated. Diversity in
      the assemblages of coexisting species is one measure of alternative outcomes of
      succession. The intermediate disturbance hypothesis proposes that a moderate
      disturbance level produces the highest levels of species diversity. Here, we use
      an agent-based model of forest development under a gradient of lightning strike
      frequency to analyse long-term dynamics of species coexistence in a multi-species
      forest. The configurations of species that result from disturbance dynamics
      reflect the interactions between life-history characteristics of the species and
      disturbance characteristics. Model results suggest that low levels of disturbance
      lead to highly ordered landscapes which exclude fire and are captured by late
      successional species. High levels of disturbance lead to oscillation between
      domination by early successional species and large disturbances. At intermediate
      levels of disturbance, the forest displays the broadest array of developmental
      pathways, highest entropy as measured by Shannon's index of diversity, and
      critical slowing near steady states. Long transients at intermediate regimes may
      reflect the working out of closely balanced constraints of competition between
      species with varying strategic adaptations to disturbance. Intermediate
      disturbance levels also result in the greatest number of alternative diversity
      configurations as outcomes of succession, reflecting an unpredictable and
      nonequilibrium forest dynamic.

PMID- 10931750
TI  - Rapid speciation via parallel, directional selection on regulatory genetic
      pathways.
AB  - Regulatory genetic pathways are ubiquitous in organisms and play a central role
      in the realization of the phenotype during development. We explored the
      proposition that these pathways can provide a plausible source of the epistatic
      variation that has been implicated in the evolution of postzygotic reproductive
      isolation. We modeled gene regulation as a matching function between the product
      of one locus and the promoter site of the next locus in the pathway, with binding
      strength determining the amount of product. When the phenotype is subject to
      parallel selection in a pair of independent populations, we find that the
      fitnesses of F(1)and F(2)hybrids often drop to very low values as the populations
      respond in genetically different and incompatible ways. The simulations support
      the predictions of the analytical models. Hybrid fitness reduction occurs more
      often as the number of loci in the pathway increases, and as the binding site
      interactions become more complex. Less hybrid fitness reduction is seen when the
      populations start with imperfect binding in the pathway. In contrast, when we
      constructed the phenotype without gene regulation using multiplicative rules,
      isomorphic to the additive phenotype commonly assumed in evolutionary models, we
      found no appreciable F(1)fitness reduction and only slight F(2)fitness reduction.
      The interaction of genetic drift and mutation, even at very high rates, did not
      reduce hybrid fitness at all on the time-scales we considered. Clearly, the
      evolution of regulatory genetic pathways can play an important role in
      speciation, but much more empirical information is needed on the effect of
      allelic variability in regulatory site interactions before this role is fully
      understood.

PMID- 10931751
TI  - Intercalation-mediated synthesis and replication: a new approach to the origin of
      life.
AB  - We propose that a molecular midwife, a flat molecule approximately 10 Ax10 A with
      two hydrophobic faces, was essential to the origin of life. This molecule was
      positively charged, water soluble and did not strongly associate with itself in
      solution. It may have been a derivative of phthalocyanine that no longer exists
      on the Earth today, and might have been formed solely from hydrogen cyanide and
      formaldehyde. The midwife tended to intercalate between side groups (bases,
      similar to those in RNA) of polymers to form stacks, which incorporated bare
      bases. The midwife alternated in these stacks with hydrogen-bonded tetrads of
      bases. Under conditions of low water activity, as in a desert during the day,
      bare bases in the stacks were joined together by neutral and chemically
      heterogeneous backbones of no fixed chirality. The components of the backbones
      were the products of the formose reaction of formaldehyde, and were involved in
      the reversible formation of N -glycosides and acetals catalysed by divalent metal
      ions. The final product of this assemblage was a fully intercalated quadruplex of
      four information-containing polymer strands (four proto -RNA molecules). This
      process constituted replication of the original polymer that had seeded the
      formation of the stack. The stack structure ensured that the polymer's base
      sequence was replicated faithfully despite the lack of both homochirality and
      chemical homogeneity in the backbone. At night, water from condensing dew would
      suddenly come in contact with these products, quenching all chemical reactions
      and releasing midwife molecules and single- or double-stranded proto-RNA.
      Evaporation of water during the day then gave new stacks containing one or two
      proto-RNA strands, bare bases, and midwife molecules, which could begin a new
      replication cycle. Our model also allows for the generation of new stacks and the
      extension of existing ones, without restricting the base sequence of either,
      thereby providing a source of genetic information. The proto-RNA replication
      cycle is driven purely by concentration changes caused by the Sun and the
      rotation of the Earth. We propose that this system as a whole could have
      gradually evolved into the RNA World.

PMID- 10931752
TI  - Comparative statics of joint reproductive allocation.
AB  - We perform a perturbation analysis (comparative statics) of how optimal
      reproductive effort and per offspring investment are jointly affected by
      different selective factors. The factors considered are: (1) mortality sources,
      classified according to affected stage (juvenile or adult) and to its nature
      (avoidable or unavoidable), and (2) resource (energy) availability for the adult
      individual. The joint approach reveals both direct and indirect effects of each
      selective pressure. These interactive effects spring from the nonlinearity of
      reproductive expenditure, separated into a part devoted to endowing offspring
      (provisioning cost) and another part invested to make reproduction possible
      (requisite cost). The latter is envisioned as a reverse sigmoid function of
      fecundity (most models, so far, have considered only the first kind of cost). The
      indirect effects have the consequence of enlarging the class of selective
      pressures that can induce changes of offspring size and clutch size, as compared
      with current explanations. So, they illuminate new causes for some effects, and
      show new effects for some well-known selective causes. Several joint patterns in
      the two variables, shown by animals and plants in the field, can thus be given
      more appropriate interpretations than traditional, piecewise, ones.

PMID- 10931753
TI  - Number of triplets in 16S rRNA gene related with pathogenicity of Bacillus spp.
      and Clostridium spp.
AB  - The relation between the number of some trinucleotides in the sequence of 16S
      rRNA gene and pathogenicity of bacterial species from the genera of Bacillus and
      Clostridium was revealed. The species of genus Bacillus, which are pathogenic for
      humans, mammals and insects, have an increased number of AAA and TAT triplets in
      16S rRNA gene. Theoretically, these species, B. anthracis and B. cereus for
      example, may be detected in the specimen by the higher ratio of AAA plus TAT
      triplets to the number of GGG triplet. Species of genus Clostridium, which are
      pathogenic for humans and mammals, have a maximum ratio of AAA and TAT triplet
      numbers. This ratio was higher than 2.6 for pathogenic species and lower than 2.2
      for saprophytic ones. These theoretical data may open a new way for detecting
      pathogenic bacteria through the determination of triplet numbers in the sequences
      of 16S rRNA or rRNA. However, the mechanism of evolutionary relation between the
      number of AAA and TAT triplets in the sequence of 16S rRNA gene and the
      pathogenicity of bacterial species is not known.

PMID- 10931754
TI  - Gene networks capable of pattern formation: from induction to reaction-diffusion.
AB  - One of the main aims of developmental biology is to understand how a single and
      apparently homogeneous egg cell achieves the intricate complexity of the adult.
      Here we present two models to explain the generation of developmental patterns
      through interactions at the gene level. One model considers direct-contact
      induction between cells while the other takes into account diffusion of hormones.
      We show that sets of cells involving identical gene networks and communicating
      through hormones spontaneously exhibit ordered patterns. We have characterized
      these patterns and the specific networks responsible for them. The models allow
      to (i) compare diffusion and direct-contact induction processes as mechanisms of
      pattern generation; (ii) identify the possible range of behaviour of real gene
      networks and (iii) suggest causal mechanisms to generate known patterns. The
      evolutionary implications are discussed.

PMID- 10931755
TI  - A dynamic game-theoretic model of parental care.
AB  - We present a model in which members of a mated pair decide whether to care for
      their offspring or desert them. There is a breeding season of finite length
      during which it is possible to produce and raise several batches of offspring. On
      deserting its offspring, an individual can search for a new mate. The probability
      of finding a mate depends on the number of individuals of each sex that are
      searching, which in turn depends upon the previous care and desertion decisions
      of all population members. We find the evolutionarily stable pattern of care over
      the breeding season. The feedback between behaviour and mating opportunity can
      result in a pattern of stable oscillations between different forms of care over
      the breeding season. Oscillations can also arise because the best thing for an
      individual to do at a particular time in the season depends on future behaviour
      of all population members. In the baseline model, a pair splits up after a
      breeding attempt, even if they both care for the offspring. In a version of the
      model in which a pair stays together if they both care, the feedback between
      behaviour and mating opportunity can lead to more than one evolutionarily stable
      form of care.

PMID- 10931756
TI  - The origin of autumn colours by coevolution.
AB  - We lack an adaptive explanation for a striking phenomenon, that of bright colours
      displayed in autumn by the leaves of many deciduous trees. The usual explanation
      is that it is simply a non-adaptive secondary effect of leaf senescence. A game
      theoretic model of biological signalling provides an adaptive hypothesis for
      autumn colours showing that they can be the result of a process of coevolution
      between insects and trees: if leaf colour acts as a warning indicator of the
      tree's vigour to autumn parasite insects, trees can gain advantage from the
      reduction of parasite load and insects can gain advantage from location of the
      most profitable hosts to lay their eggs. The results of the model are consistent
      with Zahavi's handicap principle. Possible explanations for the origin of the
      system and evidence from natural history are discussed.

PMID- 10931757
TI  - Competition and coexistence in spatially subdivided habitats.
AB  - While non-spatial models predict that like species cannot stably coexist,
      empirical studies suggest that similar species have similar distributions due to
      shared habitat requirements. A model is developed to discuss competition and
      coexistence in subdivided but locally stable habitats. The model predicts that in
      some cases it is possible for one species to exclude the other species from a
      geographic region, while in other cases two competing species can stably coexist.
      The equilibrium level and the fraction of doubly occupied patches, if there is
      coexistence, are determined by the strength of competition on colonization and
      exclusion in such a system. Also, it is possible for two ecologically identical
      species to stably coexist, and two asymmetrically competing species can coexist
      when there is a trade-off between local competition ability and invasion ability.
      When rescue effects are considered, the stable region at internal equilibrium
      point would be reduced, but the fraction of doubly occupied patches would be
      enlarged.

PMID- 10931758
TI  - Dosage, deletions and dominance: simple models of the evolution of gene
      expression.
AB  - Dominance of the wild-type allele over spontaneous null mutations, such as
      deletions, can be explained in terms of the effects of changes in enzyme dose on
      the flux of metabolic pathways. If ever increasing levels of enzyme activity have
      ever decreasing effects on the flux of the biochemical pathway, then halving of
      dosage will always have a lesser effect on flux than half the effect of complete
      removal of gene activity. Furthermore, if gene expression rates are high, then
      halving of dose can have a negligible effect on flux and dominance will be
      strong. Given that strong dominance appears to be common, this leaves open the
      issue of why enzyme activity levels are so high that a halving of expression
      rates is of minimal effect. Why produce so much surplus enzyme? One explanation,
      suggested by Haldane, is that selection favoured high expression levels as a
      defence against mutation. We model this scenario formally and show that
      protection from mutation is an extremely weak force determining expression
      levels. The selective coefficients are only of the order of the mutation rate.
      However, if we suppose a linear mapping of flux with fitness and a monotonic cost
      to increased gene expression, it follows simply that here exists an optimal level
      of gene expression. By contrast to the mutational model, doubling of gene
      expression rates when the system is distant from the optimum is associated with
      extremely high selective coefficients (orders of magnitude higher than the
      mutation rate). When the cost of gene expression is slight the optimal rate of
      expression is such that strong dominance will follow.

PMID- 10931759
TI  - Predicting the time to quasi-extinction for populations far below their carrying
      capacity.
AB  - Populations threatened by extinction are often far below their carrying capacity.
      A population collapse or quasi-extinction is defined to occur when the population
      size reaches some given lower density. If this density is chosen to be large
      enough for the demographic stochasticity to be ignored compared to environmental
      stochasticity, then the logarithm of the population size may be modelled by a
      Brownian motion until quasi-extinction occurs. The normal-gamma mixture of
      inverse Gaussian distributions can then be applied to define prediction intervals
      for the time to quasi-extinction in such processes. A similar mixture is used to
      predict the population size at a finite time for the same process provided that
      quasi-extinction has not occurred before that time. Stochastic simulations
      indicate that the coverage of the prediction interval is very close to the
      probability calculated theoretically. As an illustration, the method is applied
      to predict the time to extinction of a declining population of white stork in
      southwestern Germany.

PMID- 10931760
TI  - Genetic code origin and the strength of natural selection.

PMID- 10931761
TI  - Interaction between sequences and mixtures.

PMID- 10931762
TI  - The Turner syndrome-associated neurocognitive phenotype maps to distal Xp.
AB  - Turner syndrome (TS) is associated with a characteristic neurocognitive profile
      that includes impaired visuospatial/perceptual abilities. We used a molecular
      approach to identify a critical region of the X chromosome for neurocognitive
      aspects of TS. Partial deletions of Xp in 34 females were mapped by FISH or by
      loss of heterozygosity of polymorphic markers. Discriminant function analysis
      optimally identified the TS-associated neurocognitive phenotype. Only subjects
      missing approximately 10 Mb of distal Xp manifested the specified neurocognitive
      profile. The phenotype was seen with either paternally or maternally inherited
      deletions and with either complete or incomplete skewing of X inactivation. Fine
      mapping of informative deletions implicated a critical region of <2 Mb within the
      pseudoautosomal region (PAR1). We conclude that haploinsufficiency of PAR1
      gene(s) is the basis for susceptibility to the TS neurocognitive phenotype.

PMID- 10931764
TI  - Language processing modulated by literacy: a network analysis of verbal
      repetition in literate and illiterate subjects.
AB  - Previous behavioral and functional neuroimaging data indicate that certain
      aspects of phonological processing may not be acquired spontaneously, but are
      modulated by learning an alphabetic written language, that is, learning to read
      and write. It appears that learning an alphabetic written language modifies the
      auditory-verbal (spoken) language processing competence in a nontrivial way. We
      have previously suggested, based on behavioral and functional neuroimaging data,
      that auditory-verbal and written language interact not only during certain
      language tasks, but that learning and developing alphabetic written language
      capacities significantly modulates the spoken language system. Specifically, the
      acquisition of alphabetic orthographic knowledge has a modulatory influence on
      sublexical phonological processing and the awareness of sublexical phonological
      structure. We have suggested that developing an orthographic representation
      system for an alphabetic written language, and integrating a phoneme-grapheme
      correspondence with an existing infrastructure for auditory-verbal language
      processing, will result in a modified language network. Specifically, we suggest
      that the parallel interactive processing characteristics of the underlying
      language-processing brain network differ in literate and illiterate subjects.
      Therefore, the pattern of interactions between the regions of a suitably defined
      large-scale functional-anatomical network for language processing will differ
      between literate and illiterate subjects during certain language tasks. In order
      to investigate this hypothesis further, we analyzed the observed covariance
      structure in a PET data set from a simple auditory-verbal repetition paradigm in
      literate and illiterate subjects, with a network approach based on structural
      equation modeling (SEM). Based on a simple network model for language processing,
      the results of the present network analysis indicate that the network
      interactions during word and pseudoword repetition in the illiterate group
      differ, while there were no significant differences in the literate group. The
      differences between the two tasks in the illiterate group may reflect differences
      in attentional modulation of the language network, executive aspects of verbal
      working memory and the articulatory organization of verbal output. There were no
      significant differences between the literate and illiterate group during word
      repetition. In contrast, the network interactions differed between the literate
      and illiterate group during pseudoword repetition. In addition to differences
      similar to those observed in the illiterate group between word and pseudoword
      repetition, there were differences related to the interactions of the
      phonological loop between the groups. In particular, these differences related to
      the interaction between Broca's area and the inferior parietal cortex as well as
      the posterior-midinsula bridge between Wernicke's and Broca's area. In
      conclusion, the results of this network analysis are consistent with our
      previously presented results and support the hypothesis that learning to read and
      write during childhood influences the functional architecture of the adult human
      brain. In particular, the basic auditory-verbal language network in the human
      brain is modified as a consequence of acquiring orthographic language skills.

PMID- 10931765
TI  - Deficits in visual feature binding under isoluminant conditions.
AB  - The contribution of the magnocellular stream to visual feature binding was
      examined psychophysically through the use of isoluminant stimuli. Subjects were
      presented with three briefly flashed colored letters arranged in an array and
      asked to identify the shape and color of the center letter. The rate of illusory
      conjunctions was much higher when the letters were isoluminant with a gray
      background, compared to when the letters were either brighter or dimmer. Over 90%
      of conjunction errors involved pairing the wrong shape with the correct color,
      rather than vice versa. Directing attention to the target location with a
      nonisoluminant cue did not reduce illusory conjunctions. High rates of binding
      errors under isoluminance are interpreted here in terms of abnormalities in
      visual form processing rather than an attentional effect. In another experiment
      designed to examine the role of synchrony in feature binding, the rate of
      illusory conjunctions was highest when flanking letters were presented before the
      central target letter and not synchronously.

PMID- 10931763
TI  - Estimating Scandinavian and Gaelic ancestry in the male settlers of Iceland.
AB  - We present findings based on a study of Y-chromosome diallelic and microsatellite
      variation in 181 Icelanders, 233 Scandinavians, and 283 Gaels from Ireland and
      Scotland. All but one of the Icelandic Y chromosomes belong to haplogroup 1
      (41.4%), haplogroup 2 (34.2%), or haplogroup 3 (23.8%). We present phylogenetic
      networks of Icelandic Y-chromosome variation, using haplotypes constructed from
      seven diallelic markers and eight microsatellite markers, and we propose two new
      clades. We also report, for the first time, the phylogenetic context of the
      microsatellite marker DYS385 in Europe. A comparison of haplotypes based on six
      diallelic loci and five microsatellite loci indicates that some Icelandic
      haplogroup-1 chromosomes are likely to have a Gaelic origin, whereas for most
      Icelandic haplogroup-2 and -3 chromosomes, a Scandinavian origin is probable. The
      data suggest that 20%-25% of Icelandic founding males had Gaelic ancestry, with
      the remainder having Norse ancestry. The closer relationship with the
      Scandinavian Y-chromosome pool is supported by the results of analyses of genetic
      distances and lineage sharing. These findings contrast with results based on
      mtDNA data, which indicate closer matrilineal links with populations of the
      British Isles. This supports the model, put forward by some historians, that the
      majority of females in the Icelandic founding population had Gaelic ancestry,
      whereas the majority of males had Scandinavian ancestry.

PMID- 10931766
TI  - The influence of stimulus deviance on electrophysiologic and behavioral responses
      to novel events.
AB  - This study investigated the role of stimulus deviance in determining
      electrophysiologic and behavioral responses to "novelty." Stimulus deviance was
      defined in terms of differences either from the immediately preceding context or
      from long-term experience. Subjects participated in a visual event-related
      potential (ERP) experiment, in which they controlled the duration of stimulus
      viewing with a button press, which served as a measure of exploratory behavior.
      Each of the three experimental conditions included a frequent repetitive
      background stimulus and infrequent stimuli that deviated from the background
      stimulus. In one condition, both background and deviant stimuli were simple,
      easily recognizable geometric figures. In another condition, both background and
      deviant stimuli were unusual/unfamiliar figures, and in a third condition, the
      background stimulus was a highly unusual figure, and the deviant stimuli were
      simple, geometric shapes. Deviant stimuli elicited larger N2-P3 amplitudes and
      longer viewing durations than the repetitive background stimulus, even when the
      deviant stimuli were simple, familiar shapes and the background stimulus was a
      highly unusual figure. Compared to simple, familiar deviant stimuli, unusual
      deviant stimuli elicited larger N2-P3 amplitudes and longer viewing times. Within
      subjects, the deviant stimuli that evoked the largest N2-P3 responses also
      elicited the longest viewing durations. We conclude that deviance from both
      immediate context and long-term prior experience contribute to the response to
      novelty, with the combination generating the largest N2-P3 amplitude and the most
      sustained attention. The amplitude of the N2-P3 may reflect how much
      "uncertainty" is evoked by a novel visual stimulus and signal the need for
      further exploration and cognitive processing.

PMID- 10931767
TI  - Sex steroids modify working memory.
AB  - In the last ten years, numerous mechanisms by which sex steroids modify cortical
      function have been described. For example, estrogen replacement improves verbal
      memory in women, and animal studies have shown effects of estrogen on hippocampal
      synaptogenesis and function. Little is known about sex steroid effects on other
      aspects of memory, such as frontal lobe-mediated working memory. We examined the
      relationships between working memory and sex steroid concentrations and whether
      sex steroid supplementation would modify age-related loss of working memory in
      older men and women. Before hormone supplementation, working memory, tested with
      the Subject Ordered Pointing Test (SOP), was worse in older subjects than younger
      subjects, and there was no evidence of gender differences at either age.
      Testosterone supplementation improved working memory in older men, but a similar
      enhancement of working memory was not found in older women supplemented with
      estrogen. In men, testosterone and estrogen effects were reciprocal - with better
      working memory related to a higher testosterone to estrogen ratio. These results
      suggest that sex steroids can modulate working memory in men and can act as
      modulators of cognition throughout life.

PMID- 10931768
TI  - When far becomes near: remapping of space by tool use.
AB  - Far (extrapersonal) and near (peripersonal) spaces are behaviorally defined as
      the space outside the hand-reaching distance and the space within the hand
      reaching distance. Animal and human studies have confirmed this distinction,
      showing that space is not homogeneously represented in the brain. In this paper
      we demonstrate that the coding of space as "far" and "near" is not only
      determined by the hand-reaching distance, but it is also dependent on how the
      brain represents the extension of the body space. We will show that when the
      cerebral representation of body space is extended to include objects or tools
      used by the subject, space previously mapped as far can be remapped as near.
      Patient P.P., after a right hemisphere stroke, showed a dissociation between near
      and far spaces in the manifestation of neglect. Indeed, in a line bisection task,
      neglect was apparent in near space, but not in far space when bisection in the
      far space was performed with a projection lightpen. However, when in the far
      space bisection was performed with a stick, used by the patient to reach the
      line, neglect appeared and was as severe as neglect in the near space. An
      artificial extension of the patient's body (the stick) caused a remapping of far
      space as near space.

PMID- 10931769
TI  - The endogenous modulation of IOR is nasal-temporal asymmetric.
AB  - Inhibition of return (IOR) refers to a reflexive mechanism mediated by
      phylogenetically primitive extrageniculate visuomotor pathways, which apparently
      serves to favor novel spatial locations by inhibiting those recently sampled. We
      demonstrate an asymmetry between temporal and nasal hemifields in the strategic
      modulation of IOR by endogenously controlled attention. Exogenous and endogenous
      precues were manipulated independently on each trial such that precues to
      initiate endogenous spatial orienting were presented after IOR had been activated
      by exogenous visual signals. Both types of precues manifested their
      characteristic effects on reaction time (RT) to detect subsequent targets:
      facilitation by endogenous precues, and IOR by exogenous precues. Under monocular
      viewing, an asymmetric interaction between these two mechanisms was observed.
      While endogenous allocation of attention to the nasal hemifield reduced IOR, no
      endogenous modulation of IOR was present in the temporal hemifield where the
      effects of the two types of precues were independent. These observations suggest
      a framework for understanding the neurobiology of automaticity and control - from
      an evolutionary perspective.

PMID- 10931770
TI  - A model that accounts for activity prior to sensory inputs and responses during
      matching-to-sample tasks.
AB  - Neural network models were examined during delayed matching-to-sample tasks
      (DMS), and neurons in a monkey's prefrontal cortex were studied during the
      performance of comparable tasks. In DMS, various input stimuli follow a sample
      stimulus, and an output should occur whenever the sample reappears. Our previous
      models have been restricted to certain kinds of inputs, outputs, and temporal
      patterns. Here, we generalized the models by training them on both spatial and
      nonspatial inputs, spatial and nonspatial outputs, and both fixed and variable
      interstimulus intervals. Two versions of DMS were presented to both the model and
      the monkey, both involving nonspatial samples: (1) Two stimuli simultaneously
      appeared at a variable interval after the sample; and (2) A series of single
      stimuli appeared at fixed intervals after the sample. Both versions required
      identical spatial responses, reflecting the direction (left or right) of the
      matching stimulus relative to a central origin. Thus, these two versions of DMS
      involved the same samples, memory, and responses, but established different
      response contexts. Our analysis focused on unit activity prior to stimuli, as
      well as that prior to responses, termed anticipatory and response-related
      activity, respectively. In both the model and the monkey, anticipatory activity
      occurred only for fixed interstimulus intervals. In the model, we could determine
      that anticipatory activity acted either like a filter to suppress inappropriate
      responses or it served to enhance the network's general readiness to respond. As
      for response-related activity, units in both the model and the monkey showed
      directional selectivity and had a strong dependence on response context. In the
      model, we could show that this activity contributed both to the suppression of
      inappropriate responses and to the generation of correct ones. None of the
      model's hidden units contributed exclusively to computing the direction of match
      output. Instead, their response-related activity contributed to the computation
      of both the match decision and the correct response direction.

PMID- 10931771
TI  - Cerebral specialization for speech and non-speech stimuli in infants.
AB  - Early cerebral specialization and lateralization for auditory processing in 4
      month-old infants was studied by recording high-density evoked potentials to
      acoustical and phonetic changes in a series of repeated stimuli (either tones or
      syllables). Mismatch responses to these stimuli exhibit a distinct topography
      suggesting that different neural networks within the temporal lobe are involved
      in the perception and representation of the different features of an auditory
      stimulus. These data confirm that specialized modules are present within the
      auditory cortex very early in development. However, both for syllables and
      continuous tones, higher voltages were recorded over the left hemisphere than
      over the right with no significant interaction of hemisphere by type of stimuli.
      This suggests that there is no greater left hemisphere involvement in phonetic
      processing than in acoustic processing during the first months of life.

PMID- 10931772
TI  - Neuroanatomical substrates of arabic number processing, numerical comparison, and
      simple addition: a PET study.
AB  - Positron emission tomography was used to localize the cerebral networks
      specifically involved in three basic numerical processes: arabic numeral
      processing, numerical magnitude comparison, and retrieval of simple addition
      facts. Relative cerebral blood flow changes were measured while normal volunteers
      were resting with eyes closed, making physical judgment on nonnumerical
      characters or arabic digits, comparing, or adding the same digits. Processing
      arabic digits bilaterally produced a large nonspecific activation of occipito
      parietal areas, as well as a specific activation of the right anterior insula.
      Comparison and simple addition fact retrieval revealed a fronto-parietal network
      involving mainly the left intraparietal sulcus, the superior parietal lobule and
      the precentral gyrus. Comparison also activated, but to a lesser extent, the
      right superior parietal lobe, whereas addition also activated the orbito-frontal
      areas and the anterior insula in the right hemisphere. Implications for current
      anatomo-functional models of numerical cognition are drawn.

PMID- 10931773
TI  - A fronto-posterior network involved in visual dimension changes.
AB  - Objects characterized by a unique visual feature may pop out of their
      environment. When participants have to search for such "odd-one-out" targets,
      detection is facilitated when targets are consistently defined within the same
      feature dimension (e.g., color) compared with when the target dimension is
      uncertain (e.g., color or motion). Further, with dimensional uncertainty, there
      is a cost when a given target is defined in a different dimension to the
      preceding target, relative to when the critical dimension remains the same.
      Behavioral evidence suggests that a target dimension change involves a shift of
      attention to the new dimension. The present fMRI study revealed increased
      activation in the left frontopolar cortex, as well as in posterior visual areas
      of the dorsal and ventral streams, specific to changes in the target dimension.
      In contrast, activation in the striate cortex was decreased. This pattern
      suggests control of cross-dimensional attention shifts by the frontopolar cortex,
      modulating visual cortical processing by increased activation in higher-tier
      visual areas and suppression of activation in lower-tier areas.

PMID- 10931774
TI  - The fusiform "face area" is part of a network that processes faces at the
      individual level.
AB  - According to modular models of cortical organization, many areas of the
      extrastriate cortex are dedicated to object categories. These models often assume
      an early processing stage for the detection of category membership. Can
      functional imaging isolate areas responsible for detection of members of a
      category, such as faces or letters? We consider whether responses in three
      different areas (two selective for faces and one selective for letters) support
      category detection. Activity in these areas habituates to the repeated
      presentation of one exemplar more than to the presentation of different exemplars
      of the same category, but only for the category for which the area is selective.
      Thus, these areas appear to play computational roles more complex than detection,
      processing stimuli at the individual level. Drawing from prior work, we suggest
      that face-selective areas may be involved in the perception of faces at the
      individual level, whereas letter-selective regions may be tuning themselves to
      font information in order to recognize letters more efficiently.

PMID- 10931775
TI  - A computational model of information processing in the frontal cortex and basal
      ganglia.
AB  - Performance on the Wisconsin Card Sort Test (WCST) of patients with
      schizophrenia, Parkinson's disease (PD), and Huntington's disease (HD) was
      simulated by a neural network model constructed on principles derived from
      neuroanatomic loops from the frontal cortex through the basal ganglia and
      thalamus. The model provided a computational rationale for the empirical pattern
      of perseverative errors associated with frontal cortex dysfunction and random
      errors associated with striatal dysfunction. The model displayed perseverative
      errors in performance when the gain parameter of the activation function in units
      representing frontal cortex neurons was reduced as an analog of reduced dopamine
      release. Random errors occurred when the gain parameter of the activation
      function in units representing striatal neurons was reduced, or when the
      activation level was itself reduced as an analog of a striatal lesion. The model
      demonstrated that the perseveration of schizophrenic, Huntington's, and demented
      Parkinsonian patients may be principally due to ineffective inhibition of
      previously learned contextual rules in the frontal cortex, while the random
      errors of Parkinson's and Huntington's patients are more likely to be due to
      unsystematic errors of matching in the striatum. The model also made specific,
      empirically falsifiable predictions that can be used to explore the utility of
      these putative mechanisms of information processing in the frontal cortex and
      basal ganglia.

PMID- 10931777
TI  - Object-centered visual neglect, or relative egocentric neglect?

PMID- 10931776
TI  - Brain indices of music processing: "nonmusicians" are musical.
AB  - Only little systematic research has examined event-related brain potentials
      (ERPs) elicited by the cognitive processing of music. The present study
      investigated how music processing is influenced by a preceding musical context,
      affected by the task relevance of unexpected chords, and influenced by the degree
      and the probability of violation. Four experiments were conducted in which
      "nonmusicians" listened to chord sequences, which infrequently contained a chord
      violating the sound expectancy of listeners. Integration of in-key chords into
      the musical context was reflected as a late negative-frontal deflection in the
      ERPs. This negative deflection declined towards the end of a chord sequence,
      reflecting normal buildup of musical context. Brain waves elicited by chords with
      unexpected notes revealed two ERP effects: an early right-hemispheric
      preponderant-anterior negativity, which was taken to reflect the violation of
      sound expectancy; and a late bilateral-frontal negativity. The late negativity
      was larger compared to in-key chords and taken to reflect the higher degree of
      integration needed for unexpected chords. The early right-anterior negativity
      (ERAN) was unaffected by the task relevance of unexpected chords. The amplitudes
      of both early and late negativities were found to be sensitive to the degree of
      musical expectancy induced by the preceding harmonic context, and to the
      probability for deviant acoustic events. The employed experimental design opens a
      new field for the investigation of music processing. Results strengthen the
      hypothesis of an implicit musical ability of the human brain.

PMID- 10931778
TI  - Occupational and environmental lung diseases: an overview.

PMID- 10931779
TI  - Toxicologic methods: controlled human exposures.
AB  - The assessment of risk from exposure to environmental air pollutants is complex,
      and involves the disciplines of epidemiology, animal toxicology, and human
      inhalation studies. Controlled, quantitative studies of exposed humans help
      determine health-related effects that result from breathing the atmosphere. The
      major unique feature of the clinical study is the ability to select, control, and
      quantify pollutant exposures of subjects of known clinical status, and determine
      their effects under ideal experimental conditions. The choice of outcomes to be
      assessed in human clinical studies can be guided by both scientific and practical
      considerations, but the diversity of human responses and responsiveness must be
      considered. Subjects considered to be among the most susceptible include those
      with asthma, chronic obstructive lung disease, and cardiovascular disease. New
      experimental approaches include exposures to concentrated ambient air particles,
      diesel engine exhaust, combustion products from smoking machines, and
      experimental model particles. Future investigations of the health effects of air
      pollution will benefit from collaborative efforts among the disciplines of
      epidemiology, animal toxicology, and human clinical studies.

PMID- 10931780
TI  - Current view of epidemiologic study designs for occupational and environmental
      lung diseases.
AB  - Epidemiologic studies long have played a role in the understanding of the effects
      of the general environment and various occupational exposures on the occurrence
      of acute and chronic diseases of the lung. This article is an overview of
      epidemiologic study designs that have particular relevance to studies of
      environmental and occupational lung disease. The application of times-series
      designs in the context of epidemiologic studies is discussed, as such designs
      have become widely used in studies of health effects ambient air pollution. The
      article emphasizes recent developments in the application of case-control study
      designs, many of which have had particular applications in epidemiologic studies
      related to environmental and occupational lung disease. These case-control
      designs offer efficient and valid alternatives for studies that in the past might
      have been conducted as more costly and time-consuming cohort studies.

PMID- 10931781
TI  - Radon and lung cancer risk: taking stock at the millenium.
AB  - Radon is a well-established human carcinogen for which extensive data are
      available, extending into the range of exposures experienced by the general
      population. Mounting epidemiologic evidence on radon and lung cancer risk, now
      available from more than 20 different studies of underground miners and
      complementary laboratory findings, indicates that risks are linear in exposure
      without threshold. Radon is also a ubiquitous indoor air pollutant in homes, and
      risk projections imply that radon is the second leading cause of lung cancer
      after smoking. Recommended control strategies in the United States and other
      countries, which include testing of most homes and mitigation of those exceeding
      guideline levels, have been controversial. Further research is needed, drawing on
      molecular and cellular approaches and continuing the follow-up of the underground
      miner cohorts, and scientists should work toward constructing mechanistically
      based models that combine epidemiologic and experimental data to yield risk
      estimates with enhanced certainty.

PMID- 10931783
TI  - Outdoor allergens.
AB  - Outdoor allergens are an important part of the exposures that lead to allergic
      disease. Understanding the role of outdoor allergens requires a knowledge of the
      nature of outdoor allergen-bearing particles, the distributions of their source,
      and the nature of the aerosols (particle types, sizes, dynamics of
      concentrations). Primary sources for outdoor allergens include vascular plants
      (pollen, fern spores, soy dust), and fungi (spores, hyphae). Nonvascular plants,
      algae, and arthropods contribute small numbers of allergen-bearing particles.
      Particles are released from sources into the air by wind, rain, mechanical
      disturbance, or active discharge mechanisms. Once airborne, they follow the
      physical laws that apply to all airborne particles. Although some outdoor
      allergens penetrate indoor spaces, exposure occurs mostly outdoors. Even short
      term peak outdoor exposures can be important in eliciting acute symptoms.
      Monitoring of airborne biological particles is usually by particle impaction and
      microscopic examination. Centrally located monitoring stations give regional
      scale measurements for aeroallergen levels. Evidence for the role of outdoor
      allergens in allergic rhinitis is strong and is rapidly increasing for a role in
      asthma. Pollen and fungal spore exposures have both been implicated in acute
      exacerbations of asthma, and sensitivity to some fungal spores predicts the
      existence of asthma. Synergism and/or antagonism probably occurs with other
      outdoor air particles and gases. Control involves avoidance of exposure (staying
      indoors, preventing entry of outdoor aerosols) as well as immunotherapy, which is
      effective for pollen but of limited effect for spores. Outdoor allergens have
      been the subject of only limited studies with respect to the epidemiology of
      asthma. Much remains to be studied with respect to prevalence patterns, exposure
      and disease relationships, and control.

PMID- 10931782
TI  - Environmental tobacco smoke, indoor allergens, and childhood asthma.
AB  - Both environmental tobacco smoke and indoor allergens can exacerbate already
      established childhood albeit primarily through quite disparate mechanisms. In
      infancy and childhood, environmental tobacco smoke (ETS) exposure is associated
      with measures of decreased flow in the airways, bronchial hyperresponsiveness,
      and increased respiratory infections, but the relationship between ETS and
      allergy is poorly understood. Indoor allergens from dust mite, cockroach, and cat
      can be associated with asthma exacerbation in children sensitized to the specific
      allergens. The precise role of either ETS or indoor allergens in the development
      of asthma is less well understood. The strong and consistent association between
      ETS and asthma development in young children may relate to both prenatal and
      postnatal influences on airway caliber or bronchial responsiveness. Dust mite
      allergen levels predict asthma in children sensitized to dust mite. The tendency
      to develop specific IgE antibodies to allergens (sensitization) is associated
      with and may be preceded by the development of a T-helper (Th)2 profile of
      cytokine release. The importance of either ETS or indoor allergens in the
      differentiation of T cells into a Th2-type profile of cytokine release or in the
      localization of immediate-type allergic responses to the lung is unknown. This
      article evaluates the strength of the evidence that ETS or indoor allergens
      influence asthma exacerbation and asthma development in children. We also
      selectively review data for the effectiveness of allergen reduction in reducing
      asthma symptoms and present a potential research agenda regarding these two broad
      areas of environmental exposure and their relationship to childhood asthma.

PMID- 10931784
TI  - Exposures and health effects from inorganic agricultural dusts.
AB  - Most studies of respiratory disease from dust exposure in the agricultural
      workplace have focused on allergic diseases caused by inorganic dusts,
      specifically occupational asthma and hypersensitivity pneumonitis. Exposures to
      inorganic (mineral) dusts among farmers and farm workers may be substantial. Such
      exposures are most frequent in dry-climate farming regions. In such locations
      farming activities that perturb the soil (e.g., plowing, tilling) commonly result
      in exposures to farm operators of 1-5 mg/m(3) respirable dust and >= 20 mg/m(3)
      total dust. The composition of inorganic dust in agriculture generally reflects
      the soil composition. Crystalline silica may represent up to 20% of particles,
      and silicates represent up to 80%. These very high concentrations of inorganic
      dust are likely to explain some of the increase in chronic bronchitis reported in
      many studies of farmers. Pulmonary fibrosis (mixed dust pneumoconiosis) has been
      reported in agricultural workers, and dust samples from the lungs in these cases
      reflect the composition of agricultural soils, strongly suggesting an etiologic
      role for inorganic agricultural dusts. However, the prevalence and clinical
      severity of these cases are unknown, and many exposures are to mixed organic and
      inorganic dusts. Epidemiologic studies of farmers in diverse geographic settings
      also have observed an increase in chronic obstructive pulmonary disease morbidity
      and mortality. It is plausible that agricultural exposure to inorganic dusts is
      causally associated with chronic bronchitis, interstitial fibrosis, and chronic
      obstructive pulmonary disease, but the independent contribution of mineral dusts
      beyond the effects of organic dusts remains to be determined.

PMID- 10931785
TI  - Health effects of asbestos and nonasbestos fibers.
AB  - Exposures to asbestos and synthetic fibers remain areas of great concern in the
      field of occupational lung disease. Despite extensive study, the health effects
      associated with fibers remains an area of substantial controversy. In particular,
      effects of fibers at relatively low doses, particularly for mesothelioma, remain
      a matter of evolving opinion, especially when integrated with the divergence of
      opinion on relative pathogenicity of different fiber types. Mechanistic studies
      continue to provide a window into pathogenesis and some hope for understanding
      dose-response relationships at the lower levels seen in contemporary Western
      workplaces and the general environment. Changes in clinical assessment based on
      use of new chest imaging techniques beyond the traditional plain film are also an
      area of evolution and begin to challenge B-reading as the definitive tool for
      noninvasive assessment of disease. Public health concerns have to a great extent
      been transported to the developing world where there is a strong trend toward
      increased use of asbestos, although it has been virtually eliminated from
      commerce in most developed countries. For nonasbestos fibers, the major unsettled
      issues are their relative potencies as carcinogens for the human lung and
      mesothelium and the need to sort out the relation between physical and chemical
      properties of these fibers and their pathogenicity. The recent discovery of
      "flock worker's lung" due to synthetic fibers once again alerts us to emerging
      diseases associated with new technologies.

PMID- 10931786
TI  - Silicosis and coal workers' pneumoconiosis.
AB  - Exposure to coal mine dust and/or crystalline silica results in pneumoconiosis
      with initiation and progression of pulmonary fibrosis. This review presents
      characteristics of simple and complicated coal workers' pneumoconiosis (CWP) as
      well as pathologic indices of acute and chronic silicosis by summarizing results
      of in vitro, animal, and human investigations. These results support four basic
      mechanisms in the etiology of CWP and silicosis: a) direct cytotoxicity of coal
      dust or silica, resulting in lung cell damage, release of lipases and proteases,
      and eventual lung scarring; b) activation of oxidant production by pulmonary
      phagocytes, which overwhelms the antioxidant defenses and leads to lipid
      peroxidation, protein nitrosation, cell injury, and lung scarring; c) activation
      of mediator release from alveolar macrophages and epithelial cells, which leads
      to recruitment of polymorphonuclear leukocytes and macrophages, resulting in the
      production of proinflammatory cytokines and reactive species and in further lung
      injury and scarring; d) secretion of growth factors from alveolar macrophages and
      epithelial cells, stimulating fibroblast proliferation and eventual scarring.
      Results of in vitro and animal studies provide a basis for proposing these
      mechanisms for the initiation and progression of pneumoconiosis. Data obtained
      from exposed workers lend support to these mechanisms.

PMID- 10931787
TI  - Inorganic dust pneumonias: the metal-related parenchymal disorders.
AB  - In recent years the greatest progress in our understanding of pneumoconioses,
      other than those produced by asbestos, silica, and coal, has been in the arena of
      metal-induced parenchymal lung disorders. Inhalation of metal dusts and fumes can
      induce a wide range of lung pathology, including airways disorders, cancer, and
      parenchymal diseases. The emphasis of this update is on parenchymal diseases
      caused by metal inhalation, including granulomatous disease, giant cell
      interstitial pneumonitis, chemical pneumonitis, and interstitial fibrosis, among
      others. The clinical characteristics, epidemiology, and pathogenesis of disorders
      arising from exposure to aluminum, beryllium, cadmium, cobalt, copper, iron,
      mercury, and nickel are presented in detail. Metal fume fever, an inhalation
      fever syndrome attributed to exposure to a number of metals, is also discussed.
      Advances in our knowledge of antigen-specific immunologic reactions in the lung
      are particularly evident in disorders secondary to beryllium and nickel exposure,
      where immunologic mechanisms have been well characterized. For example, current
      evidence suggests that beryllium acts as an antigen, or hapten, and is presented
      by antigen-presenting cells to CD4+ T cells, which possess specific surface
      antigen receptors. Other metals such as cadmium and mercury induce nonspecific
      damage, probably by initiating production of reactive oxygen species.
      Additionally, genetic susceptibility markers associated with increased risk have
      been identified in some metal-related diseases such as chronic beryllium disease
      and hard metal disease. Future research needs include development of biologic
      markers of metal-induced immunologic disease, detailed characterization of human
      exposure, examination of gene alleles that might confer risk, and association of
      exposure data with that of genetic susceptibility.

PMID- 10931788
TI  - Occupational asthma: a review.
AB  - Occupational asthma is the most common form of occupational lung disease in the
      developed world at the present time. In this review, the epidemiology,
      pathogenesis/mechanisms, clinical presentations, management, and prevention of
      occupational asthma are discussed. The population attributable risk of asthma due
      to occupational exposures is considerable. Current understanding of the
      mechanisms by which many agents cause occupational asthma is limited, especially
      for low-molecular-weight sensitizers and irritants. The diagnosis of occupational
      asthma is generally established on the basis of a suggestive history of a
      temporal association between exposure and the onset of symptoms and objective
      evidence that these symptoms are related to airflow limitation. Early diagnosis,
      elimination of exposure to the responsible agent, and early use of inhaled
      steroids may play important roles in the prevention of long-term persistence of
      asthma. Persistent occupational asthma is often associated with substantial
      disability and consequent impacts on income and quality of life. Prevention of
      new cases is the best approach to reducing the burden of asthma attributable to
      occupational exposures. Future research needs are identified.

PMID- 10931789
TI  - Agricultural lung diseases.
AB  - Agriculture is considered one of the most hazardous occupations. Organic dusts
      and toxic gases constitute some of the most common and potentially disabling
      occupational and environmental hazards. The changing patterns of agriculture have
      paradoxically contributed to both improved working conditions and increased
      exposure to respiratory hazards. Animal confinement operations with increasing
      animal density, particularly swine confinement, have contributed significantly to
      increased intensity and duration of exposure to indoor air toxins. Ongoing
      research has implicated bacterial endotoxins, fungal spores, and the inherent
      toxicity of grain dusts as causes of upper and lower airway inflammation and as
      immunologic agents in both grain and animal production. Animal confinement gases,
      particularly ammonia and hydrogen sulfide, have been implicated as additional
      sources of respiratory irritants. It has become evident that a significant
      percentage of agricultural workers have clinical symptoms associated with long
      term exposure to organic dusts and animal confinement gases. Respiratory diseases
      and syndromes, including hypersensitivity pneumonitis, organic dust toxic
      syndrome, chronic bronchitis, mucous membrane inflammation syndrome, and
      asthmalike syndrome, result from ongoing acute and chronic exposures. In this
      review we focus upon the emerging respiratory health issues in a changing
      agricultural economic and technologic environment. Environmental and occupational
      hazards and exposures will be emphasized rather than clinical diagnosis and
      treatment. Methods of prevention, from both engineering controls and personal
      respiratory perspectives, are also addressed.

PMID- 10931790
TI  - Epidemiology of fine particulate air pollution and human health: biologic
      mechanisms and who's at risk?
AB  - This article briefly summarizes the epidemiology of the health effects of fine
      particulate air pollution, provides an early, somewhat speculative, discussion of
      the contribution of epidemiology to evaluating biologic mechanisms, and evaluates
      who's at risk or is susceptible to adverse health effects. Based on preliminary
      epidemiologic evidence, it is speculated that a systemic response to fine
      particle-induced pulmonary inflammation, including cytokine release and altered
      cardiac autonomic function, may be part of the pathophysiologic mechanisms or
      pathways linking particulate pollution with cardiopulmonary disease. The elderly,
      infants, and persons with chronic cardiopulmonary disease, influenza, or asthma
      are most susceptible to mortality and serious morbidity effects from short-term
      acutely elevated exposures. Others are susceptible to less serious health effects
      such as transient increases in respiratory symptoms, decreased lung function, or
      other physiologic changes. Chronic exposure studies suggest relatively broad
      susceptibility to cumulative effects of long-term repeated exposure to fine
      particulate pollution, resulting in substantive estimates of population average
      loss of life expectancy in highly polluted environments. Additional knowledge is
      needed about the specific pollutants or mix of pollutants responsible for the
      adverse health effects and the biologic mechanisms involved.

PMID- 10931791
TI  - Specific and nonspecific obstructive lung disease in childhood: causes of changes
      in the prevalence of asthma.
AB  - Reversible airway obstruction in childhood includes two major groups of patients:
      those with recurrent wheezing following bronchiolitis in early childhood, and
      those with allergic asthma, which represents an increasingly large proportion of
      cases through the school years. Over the last 40 years of the 20th century,
      allergic asthma has increased in many countries and in relation to several
      different allergens. Although this increase has differed in magnitude in
      different countries and also in the social groups most affected, it has had
      several features in common. The increase generally started between 1960 and 1970,
      has been progressive since then, and has continued into the 1990s without a
      defined peak. Among children 5-18 years of age, the increase has predominantly
      been among allergic individuals. Theories about the causes of the increase in
      asthma have focused on two scenarios: a) that changes in houses combined with
      increased time spent indoors have increased exposure to relevant allergens, or b)
      that changes in diet, antibiotic use, immunizations, and the pattern of
      infections in childhood have led to a change in immune responsiveness such that a
      larger section of the population makes T(H)2, rather than T(H)1 responses
      including IgE antibodies to inhalant allergens. There are, however, problems with
      each of these theories and, in particular, none of the proposed changes can
      explain the progressive nature of the increase over 40 years. The fact that the
      change in asthma has much in common with epidemic increase in diseases such as
      Type II diabetes or obesity suggests that similar factors could be involved.
      Several lines of evidence are reviewed that suggest that the decline in physical
      activity of children, particularly those living in poverty in the United States,
      could have contributed to the rise in asthma. The hypothesis would be that the
      progressive loss of a lung-specific protective effect against wheezing has
      allowed allergic children to develop symptomatic asthma. What is clear is that
      current theories do not provide either an adequate explanation of the increase or
      a practical approach to reversing the current trend.

PMID- 10931793
TI  - Outdoor air pollution and lung cancer.
AB  - In the 1950s evidence of an ongoing epidemic of lung cancer in the United States
      and Western Europe led researchers to examine the role of outdoor air pollution,
      which was considered by some to be a likely cause. Although epidemiologic
      research quickly identified the central role of cigarette smoking in this
      epidemic, and despite progress in reducing outdoor air pollution in Western
      industrialized countries, concerns that ambient air pollution is causing lung
      cancer have persisted to the present day. This concern is based on the fact that
      known carcinogens continue to be released into outdoor air from industrial
      sources, power plants, and motor vehicles, and on a body of epidemiologic
      research that provides some evidence for an association between outdoor air
      pollution and lung cancer. This article reviews the epidemiologic evidence for
      this association and discusses the limitations of current studies for estimating
      the lung cancer risk in the general population. It also identifies research needs
      and suggests possible approaches to addressing outstanding questions.

PMID- 10931795
TI  - : august 8, 2000

PMID- 10931792
TI  - Environmental and genetic risk factors and gene-environment interactions in the
      pathogenesis of chronic obstructive lung disease.
AB  - Current understanding of the pathogenesis of chronic obstructive pulmonary
      disease (COPD), a source of substantial morbidity and mortality in the United
      States, suggests that chronic inflammation leads to the airways obstruction and
      parenchymal destruction that characterize this condition. Environmental factors,
      especially tobacco smoke exposure, are known to accelerate longitudinal decline
      of lung function, and there is substantial evidence that upregulation of
      inflammatory pathways plays a vital role in this process. Genetic regulation of
      both inflammatory responses and anti-inflammatory protective mechanisms likely
      underlies the heritability of COPD observed in family studies. In alpha-1
      protease inhibitor deficiency, the only genetic disorder known to cause COPD,
      lack of inhibition of elastase activity, results in the parenchymal destruction
      of emphysema. Other genetic polymorphisms have been hypothesized to alter the
      risk of COPD but have not been established as causes of this condition. It is
      likely that multiple genetic factors interacting with each other and with a
      number of environmental agents will be found to result in the development of
      COPD.

PMID- 10931796
TI  - Alcohol septal ablation in hypertrophic obstructive cardiomyopathy: the need for
      a registry.

PMID- 10931797
TI  - Smoking increases tissue factor expression in atherosclerotic plaques:
      implications for plaque thrombogenicity.
AB  - BACKGROUND: Smoking increases the risk of atherothrombotic events. To determine
      whether smoking influences plaque thrombogenicity, we examined the effect of
      cigarette smoking and aspirin use on tissue factor (TF) expression in
      atherosclerotic plaques. METHODS AND RESULTS: A total of 23 apoE-/- mice were
      exposed to cigarette smoke with (n=9) or without (n=14) aspirin treatment. Eleven
      mice who were exposed to filtered room air served as controls. Aortic root
      plaques of mice exposed to smoke had higher immunoreactivity for TF (14+/-4%
      versus 6.4+/-3%; P=0.0005), vascular cell adhesion molecule-1 (15+/-4% versus 5+/
      2%; P=0.002), and macrophages (16+/-5% versus 6+/-2%; P=0.002) compared with
      nonsmoking controls. Aspirin treatment attenuated smoking-induced changes in
      plaque composition. In human plaques obtained by carotid endarterectomy, TF
      immunoreactivity (8+/-5% versus 2+/-2%; P=0.0002) and activity (P=0. 03) were
      higher in the plaques from smokers (n=28) than those from nonsmokers (n=28).
      Aspirin use was associated with reduced TF expression in smokers (9+/-8% versus
      3+/-4%; P=0.0017). CONCLUSIONS: Our results suggest increased plaque TF
      expression and thrombogenicity as a novel mechanism for the increased risk of
      atherothrombotic events in smokers. Treatment with aspirin may reduce TF
      expression.

PMID- 10931794
TI  - Interstitial fibrosis and growth factors.
AB  - Interstitial pulmonary fibrosis (IPF) is scarring of the lung caused by a variety
      of inhaled agents including mineral particles, organic dusts, and oxidant gases.
      The disease afflicts millions of individuals worldwide, and there are no
      effective therapeutic approaches. A major reason for this lack of useful
      treatments is that few of the molecular mechanisms of disease have been defined
      sufficiently to design appropriate targets for therapy. Our laboratory has
      focused on the molecular mechanisms through which three selected peptide growth
      factors could play a role in the development of IPF. Hundreds of growth factors
      and cytokines could be involved in the complex disease process. We are studying
      platelet-derived growth factor because it is the most potent mesenchymal cell
      mitogen yet described, transforming growth factor beta because it is a powerful
      inducer of extracellular matrix (scar tissue) components by mesenchymal cells,
      and tumor necrosis factor alpha because it is a pleiotropic cytokine that we and
      others have shown is essential for the development of IPF in animal models. This
      review describes some of the evidence from studies in humans, in animal models,
      and in vitro, that supports the growth factor hypothesis. The use of modern
      molecular and transgenic technologies could elucidate those targets that will
      allow effective therapeutic approaches.

PMID- 10931798
TI  - Effect of plasma homocysteine concentration on early and late events in patients
      with acute coronary syndromes.
AB  - BACKGROUND: Although a raised plasma homocysteine is a risk factor for vascular
      disease, it is not known whether it is associated with an adverse cardiac outcome
      in patients admitted with acute coronary syndromes. We evaluated the relationship
      between plasma homocysteine and short-term (28 days) and long-term (median 2.5
      years) prognosis in acute coronary syndromes. METHODS AND RESULTS: We evaluated
      the relationship of quintiles of homocysteine to fatal and nonfatal coronary
      disease early (28 days) and late (29 days to a median of 2. 5 years) after
      admission to a single unit of patients with unstable angina (n=204) and
      myocardial infarction (n=236). The end points studied were cardiac death (n=67)
      and/or myocardial (re)infarction (n=30). Cox regression and logistic regression
      were used to estimate the relationship of homocysteine to coronary events. The
      event rate within the first 28 days (22 cardiac deaths and 5 nonfatal
      infarctions) was not related to the admission homocysteine level. In the 203
      unstable angina and 214 myocardial infarction survivors, an apparent threshold
      effect was seen on long-term follow-up, with a significant step-up in the
      frequency of events between the lowest 3 quintiles (14 cardiac deaths and 11
      nonfatal infarctions) and the upper 2 quintiles (31 fatal and 12 nonfatal
      events). Patients in the upper 2 quintiles (>12.2 micromol/L) had a 2.6-fold
      increase in the risk of a cardiac event (95% CI, 1.5 to 4.3, P<0.001).
      CONCLUSIONS: Elevated total homocysteine levels on admission strongly predict
      late cardiac events in acute coronary syndromes.

PMID- 10931799
TI  - Acute coronary findings at autopsy in heart failure patients with sudden death:
      results from the assessment of treatment with lisinopril and survival (ATLAS)
      trial.
AB  - BACKGROUND: Sudden unexpected death frequently occurs in chronic heart failure.
      The importance of acute coronary events in triggering sudden death (SD) is
      unclear. METHODS AND RESULTS: We evaluated at autopsy the prevalence of acute
      coronary findings (coronary thrombus, ruptured plaque, or myocardial infarction
      [MI]) and their relation to SD. Autopsy results in 171 patients in the randomized
      ATLAS trial were reviewed. The prevalence of acute coronary findings was 33%: in
      54% of patients with significant coronary artery disease (CAD) who died suddenly,
      32% who died of myocardial failure, but in non-CAD patients, they were present in
      only 5% and 10% respectively. The percentage of patients classified as dying of
      MI was 28% in the autopsy group versus 4% in the nonautopsied group (P<0.0001).
      Of the autopsied group with acute MI, 97% (31 of 32 patients) with SD and 40% (6
      of 15 patients) with myocardial failure did not have the MI diagnosed during
      life. When undiagnosed MI was classified as "sudden unexpected" or "myocardial
      failure" from clinical information only, the distribution of death causes was
      similar in the autopsy and nonautopsied groups. CONCLUSIONS: Acute coronary
      findings are frequent and usually not clinically diagnosed in heart failure
      patients with CAD, particularly in those dying suddenly, suggesting the
      importance of acute coronary events as a trigger for SD in this setting.

PMID- 10931800
TI  - Characterization of plaque components with intravascular ultrasound elastography
      in human femoral and coronary arteries in vitro.
AB  - BACKGROUND: The composition of plaque is a major determinant of coronary-related
      clinical syndromes. Intravascular ultrasound (IVUS) elastography has proven to be
      a technique capable of reflecting the mechanical properties of phantom material
      and the femoral arterial wall. The aim of this study was to investigate the
      capability of intravascular elastography to characterize different plaque
      components. METHODS AND RESULTS: Diseased human femoral (n=9) and coronary (n=4)
      arteries were studied in vitro. At each location (n=45), 2 IVUS images were
      acquired at different intraluminal pressures (80 and 100 mm Hg). With the use of
      cross-correlation analysis on the high-frequency (radiofrequency) ultrasound
      signal, the local strain in the tissue was determined. The strain was color-coded
      and plotted as an additional image to the IVUS echogram. The visualized segments
      were stained on the presence of collagen, smooth muscle cells, and macrophages.
      Matching of elastographic data and histology were performed with the use of the
      IVUS echogram. The cross sections were segmented in regions (n=125) that were
      based on the strain value on the elastogram. The dominant plaque types in these
      regions (fibrous, fibro-fatty, or fatty) were obtained from histology and
      correlated with the average strain and echo intensity. The strain for the 3
      plaque types as determined by histology differed significantly (P=0.0002). This
      difference was mainly evident between fibrous and fatty tissue (P=0.0004). The
      plaque types did not reveal echo-intensity differences in the IVUS echogram
      (P=0.882). CONCLUSIONS: Different strain values are found between fibrous, fibro
      fatty, and fatty plaque components, indicating the potential of intravascular
      elastography to distinguish different plaque morphologies.

PMID- 10931801
TI  - Double-blind study of the safety of clopidogrel with and without a loading dose
      in combination with aspirin compared with ticlopidine in combination with aspirin
      after coronary stenting : the clopidogrel aspirin stent international cooperative
      study (CLASSICS).
AB  - BACKGROUND: Combination therapy with the ADP receptor antagonist ticlopidine plus
      aspirin has emerged as standard care after coronary stenting. Clopidogrel, a new
      ADP receptor antagonist, has greater molar potency than ticlopidine and better
      safety/tolerability. METHODS AND RESULTS: Patients (n=1020) were randomized after
      successful stent placement and initiated on a 28-day regimen of either (1) 300-mg
      clopidogrel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d
      clopidogrel and 325 mg/d aspirin; (2) 75 mg/d clopidogrel and 325 mg/d aspirin;
      or (3) 250 mg BID ticlopidine and 325 mg/d aspirin. The primary end point
      consisted of major peripheral or bleeding complications, neutropenia,
      thrombocytopenia, or early discontinuation of study drug as the result of a
      noncardiac adverse event during the study-drug treatment period. The primary end
      point occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% of
      patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95% CI
      0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac
      death, myocardial infarction, target lesion revascularization) were low and
      comparable between treatment groups (0.9% with ticlopidine, 1.5% with 75 mg/d
      clopidogrel, 1.2% with the clopidogrel loading dose; P=NS for all comparisons).
      CONCLUSIONS: The safety/tolerability of clopidogrel (plus aspirin) is superior to
      that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well
      tolerated, notably with no increased risk of bleeding. Secondary end point data
      are consistent with the hypothesis that clopidogrel and ticlopidine have
      comparable efficacy with regard to cardiac events after successful stenting.

PMID- 10931802
TI  - Inadequate response to treatment in coronary heart disease : adverse effects of
      type D personality and younger age on 5-year prognosis and quality of life.
AB  - BACKGROUND: Improvement in treatment of patients with coronary heart disease
      (CHD) has caused longer survival but also an increase in the number of patients
      at risk for subsequent cardiac events and impaired quality of life (QOL). We
      hypothesized that chronic emotional distress confers an increased risk of poor
      outcome despite appropriate treatment. METHODS AND RESULTS: This prospective
      study examined the 5-year prognosis of 319 patients with CHD. Baseline assessment
      included symptoms of depression/anxiety and distressed personality type (type D
      ie, high negative affectivity and social inhibition). The main end points were
      cardiac death or nonfatal myocardial infarction and impaired QOL. There were 22
      cardiac events (16 nonfatal); they were related to left ventricular ejection
      fraction (LVEF) </=50%, poor exercise tolerance, age </=55 years, symptoms of
      depression, and type D personality. Multivariate analysis yielded LVEF </=50%
      (OR, 3.9; P=0.009), type D personality (OR, 8.9; P=0.0001), and age </=55 years
      (OR, 2.6; P=0.05) as independent predictors of cardiac events. Convergence of
      these risk factors predicted the absence of the expected therapeutic response
      that was observed in 10% of the patients. When 2 or 3 risk factors occurred
      together, the rate of poor outcome was 4-fold higher (P=0. 0001). Estimates of
      medical costs increased progressively with an increasing number of risk factors.
      Smoking, symptoms of depression, and type D personality were independent
      predictors of impaired QOL. CONCLUSIONS: Decreased LVEF, type D personality, and
      younger age increase the risk of cardiac events; convergence of these factors
      predicts nonresponse to treatment. Emotionally stressed and younger patients with
      CHD represent high-risk groups deserving of special study.

PMID- 10931803
TI  - PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial
      infarction in humans.
AB  - BACKGROUND: Inflammation is an important component of ischemic heart disease.
      PTX3 is a long pentraxin whose expression is induced by cytokines in endothelial
      cells, mononuclear phagocytes, and myocardium. The possibility that PTX3 is
      altered in patients with acute myocardial infarction (AMI) has not yet been
      tested. METHODS AND RESULTS: Blood samples were collected from 37 patients
      admitted to the coronary care unit (CCU) with symptoms of AMI. PTX3 plasma
      concentrations, as measured by ELISA, higher than the mean+2 SD of age-matched
      controls (2.01 ng/mL) were found in 27 patients within the first 24 hours of CCU
      admission. PTX3 peaked at 7.5 hours after CCU admission, and mean peak
      concentration was 6.94+/-11.26 ng/mL. Plasma concentrations of PTX3 returned to
      normal in all but 3 patients at hospital discharge and were unrelated to AMI site
      or extent, Killip class at entry, hours from symptom onset, and thrombolysis. C
      reactive protein peaked in plasma at 24 hours after CCU admission, much later
      than PTX3 (P<0.001). Patients >64 years old and women had significantly higher
      PTX3 concentrations at 24 hours (P<0.05). PTX3 was detected by
      immunohistochemistry in normal but not in necrotic myocytes. CONCLUSIONS: PTX3 is
      present in the intact myocardium, increases in the blood of patients with AMI,
      and disappears from damaged myocytes. We suggest that PTX3 is an early indicator
      of myocyte irreversible injury in ischemic cardiomyopathy.

PMID- 10931804
TI  - Race, sex, poverty, and the medical treatment of acute myocardial infarction in
      the elderly.
AB  - BACKGROUND: Race, sex, and poverty are associated with the use of diagnostic
      cardiac catheterization and coronary revascularization during treatment of acute
      myocardial infarction (AMI). However, the association of sociodemographic
      characteristics with the use of less costly, more readily available medical
      therapies remains poorly characterized. METHODS AND RESULTS: We evaluated 169 079
      Medicare beneficiaries >/=65 years of age treated for AMI between January 1994
      and February 1996 to determine the association of patient race, sex, and poverty
      with the use of medical therapy. Multivariable regression models were constructed
      to evaluate the unadjusted and adjusted influence of sociodemographic
      characteristics on the use of 2 admission (aspirin, reperfusion) and 2 discharge
      therapies (aspirin, beta-blockers) indicated during the treatment of AMI. Therapy
      use varied by patient race, sex, and poverty status. Black patients were less
      likely to undergo reperfusion (RR 0.84, 95% CI 0. 78, 0.91) or receive aspirin on
      admission (RR 0.97, 95% CI 0.96, 0. 99) and beta-blockers (RR 0.94, 95% CI 0.88,
      1.00) at discharge. Female patients were less likely to receive aspirin on
      admission (RR 0.98, 95% CI 0.97, 0.99) and discharge (RR 0.98, 95% CI 0.96,
      0.99). Poor patients were less likely to receive aspirin (RR 0.97, 95% CI 0. 96,
      0.98) or reperfusion (RR 0.97, 95% CI 0.93, 1.00) on admission and aspirin (RR
      0.98, 95% CI 0.96, 1.00), or beta-blockers (RR 0.95, 95% CI 0.91, 0.99) on
      discharge. CONCLUSIONS: Medical therapies are currently underused in the
      treatment of black, female, and poor patients with AMI.

PMID- 10931805
TI  - Sudden cardiac death with apparently normal heart.
AB  - BACKGROUND: Mechanisms of sudden cardiac death (SCD) in subjects with apparently
      normal hearts are poorly understood. In survivors, clinical investigations may
      not establish normal cardiac structure with certainty. Large autopsy series may
      provide a unique opportunity to confirm structural normalcy of the heart before
      reviewing a patient's clinical history. METHODS AND RESULTS: We identified and
      reexamined structurally normal hearts from a 13-year series of archived hearts of
      patients who had sudden cardiac death. Subsequently, for each patient with a
      structurally normal heart, a detailed review of the circumstances of death as
      well as clinical history was performed. Of 270 archived SCD hearts identified,
      190 were male and 80 female (mean age 42 years); 256 (95%) had evidence of
      structural abnormalities and 14 (5%) were structurally normal. In the group with
      structurally normal hearts (mean age 35 years), SCD was the first manifestation
      of disease in 7 (50%) of the 14 cases. In 6 cases, substances were identified in
      serum at postmortem examination without evidence of drug overdose; 2 of these
      chemicals have known associations with SCD. On analysis of ECGs, preexcitation
      was found in 2 cases. Comorbid conditions identified were seizure disorder and
      obesity (2 cases each). In 6 cases, there were no identifiable conditions
      associated with SCD. CONCLUSIONS: In 50% of cases of SCD with structurally normal
      hearts, sudden death was the first manifestation of disease. An approach
      combining archived heart examinations with detailed review of the clinical
      history was effective in elucidating potential SCD mechanisms in 57% of cases.

PMID- 10931806
TI  - Differentiation between restrictive cardiomyopathy and constrictive pericarditis
      by early diastolic doppler myocardial velocity gradient at the posterior wall.
AB  - BACKGROUND: The differential diagnosis between restrictive cardiomyopathy (RCM)
      and constrictive pericarditis (CP) is challenging and, despite combined
      information from different diagnostic tests, surgical exploration is often
      necessary. METHODS AND RESULTS: A group of 55 subjects (mean age, 63+/-11 years;
      36 men and 19 women) were enrolled in the study; 15 had RCM, 10 had CP, and 30
      were age-matched, normal controls. The diagnosis of RCM was supported by a
      biopsy; in the CP group, the diagnosis was confirmed either surgically or at
      autopsy. All patients underwent a transthoracic echocardiogram that included the
      assessment of Doppler myocardial velocity gradient (MVG), as measured from the
      left ventricular posterior wall during the predetermined phases of the cardiac
      cycle. MVG was lower (P<0.01) in RCM patients compared with both CP patients and
      normal controls during ventricular ejection (2. 8+/-1.2 versus 4.4+/-1.0 and
      4.7+/-0.8 s(-1), respectively) and rapid ventricular filling (1.9+/-0.8 versus
      8.7+/-1.7 and 3.7+/-1.4 s(-1), respectively). Additionally, during isovolumic
      relaxation, MVG was positive in RCM patients and negative in both CP patients and
      normal controls (0.7+/-0.4 versus -1.0+/-0.6 and -0.4+/-0.3 s(-1), respectively;
      P<0.01). During atrial contraction, MVG was similarly low (P<0.01) in both RCM
      and CP patients compared with normal controls (1.6+/-1.7 and 1.7+/-1.8 versus
      3.8+/-0.9 s(-1), respectively). CONCLUSIONS: Doppler myocardial imaging-derived
      MVG, as measured from the left ventricular posterior wall in early diastole
      during both isovolumic relaxation and rapid ventricular filling, allows for the
      discrimination of RCM from CP.

PMID- 10931807
TI  - Clinical features of hypertrophic cardiomyopathy caused by a Lys183 deletion
      mutation in the cardiac troponin I gene.
AB  - BACKGROUND: Mutations that cause hypertrophic cardiomyopathy (HCM) have been
      identified in 9 genes that code proteins in the sarcomere. Previous reports have
      demonstrated that cardiac troponin I (cTnI) gene mutations may account for
      familial HCM; however, the clinical characteristics and prognosis of patients
      with HCM caused by cTnI gene mutations are not known. METHODS AND RESULTS: We
      analyzed cTnI gene mutations in 130 unrelated probands with HCM and their
      families to clarify the genotype-phenotype correlations. We identified 25
      individuals in 7 families with a Lys183 deletion (Lys183 del) mutation in exon 7
      of the cTnI gene. The disease penetrance in subjects aged >20 years was 88% by
      echocardiography and 96% by ECG. Sudden death occurred in 7 individuals of 4
      families at any age. Overall, 7 (43.8%) of 16 individuals aged >40 years had left
      ventricular systolic dysfunction, and 3 (18.8%) displayed dilated cardiomyopathy
      like features. Of affected individuals, 4 of 5 individuals aged >40 years
      followed by echocardiography showed septal thinning and decreased fractional
      shortening during >5 years of follow-up. CONCLUSIONS: The Lys183 del mutation in
      the cTnI gene in patients with HCM is associated with variable clinical features
      and outcomes. HCM caused by the Lys183 del mutation has a significant disease
      penetrance. This mutation is associated with sudden death at any age and dilated
      cardiomyopathy-like features in those aged >40 years. However, it remains unclear
      whether screening of families with HCM for this mutation will be useful in
      patient management and counseling.

PMID- 10931808
TI  - Remnant lipoproteins induce proatherothrombogenic molecules in endothelial cells
      through a redox-sensitive mechanism.
AB  - BACKGROUND: Triglyceride-rich lipoproteins (TGLs) are atherogenic. However, their
      cellular mechanisms remain largely unexplained. This study examined the effects
      of isolated remnant-like lipoprotein particles (RLPs) on the expression of
      intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1
      (VCAM-1), and tissue factor (TF), proatherothrombogenic molecules, in cultured
      human endothelial cells. METHODS AND RESULTS: RLPs were isolated from plasma of
      hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti
      apoA-1 and anti-apoB-100 monoclonal antibodies. The incubation of cells with RLPs
      significantly upregulated mRNA and protein expression of these molecules. Total
      TGLs (d<1.006) and LDL had fewer or minimal effects on expression of these
      molecules compared with RLPs. RLPs increased intracellular oxidant levels, as
      assessed with an oxidant-sensitive probe. Combined incubation with alpha
      tocopherol or N-acetylcysteine, both antioxidants, suppressed RLP-induced
      increase in expression of these molecules. In patients with higher plasma levels
      of RLPs, plasma levels of soluble forms of ICAM-1 and VCAM-1 were significantly
      higher than in patients with lower RLP levels. Treatment with alpha-tocopherol
      for 1 month decreased levels of the soluble adhesion molecules concomitantly with
      an increase in resistance of RLPs to oxidative modification in patients with high
      RLP levels. CONCLUSIONS: RLPs upregulated endothelial expression of ICAM-1, VCAM
      1, and TF, proatherothrombogenic molecules, partly through a redox-sensitive
      mechanism. RLPs may have an important role in atherothrombotic complications in
      hypertriglyceridemic patients.

PMID- 10931809
TI  - Nebivolol: a third-generation beta-blocker that augments vascular nitric oxide
      release: endothelial beta(2)-adrenergic receptor-mediated nitric oxide
      production.
AB  - BACKGROUND: Nebivolol is a beta(1)-selective adrenergic receptor antagonist with
      proposed nitric oxide (NO)-mediated vasodilating properties in humans. In this
      study, we explored whether nebivolol indeed induces NO production and, if so, by
      what mechanism. We hypothesized that not nebivolol itself but rather its
      metabolites augment NO production. METHODS AND RESULTS: Mouse thoracic aorta
      segments were bathed in an organ chamber. Administration of nebivolol did not
      affect NO production. When nebivolol was allowed to metabolize in vivo in mice,
      addition of plasma of these mice caused a sustained 2-fold increase in NO
      release. Interestingly, coadministration of a selective beta(2)-adrenergic
      receptor antagonist (butoxamine) prevented the response. Immunohistochemistry and
      Western blot analysis demonstrated the presence of beta(2)- but not beta(1)
      adrenergic receptors on endothelial cells. In the absence of calcium, metabolized
      nebivolol failed to increase NO production, suggesting a role for calcium
      dependent NO synthase. With digital fluorescence imaging, a rapid and sustained
      rise in endothelial cytosolic free Ca(2+) concentration was observed after
      administration of metabolized nebivolol, which also was abrogated by butoxamine
      pretreatment. CONCLUSIONS: In vivo metabolized nebivolol increases vascular NO
      production. This phenomenon involves endothelial beta(2)-adrenergic receptor
      ligation, with a subsequent rise in endothelial free [Ca(2+)](i) and endothelial
      NO synthase-dependent NO production. This may be an important mechanism
      underlying the nebivolol-induced, NO-mediated arterial dilation in humans.

PMID- 10931810
TI  - Estimates of repolarization dispersion from electrocardiographic measurements.
AB  - BACKGROUND: Repolarization dispersion (Rd) is frequently mentioned as a predictor
      of cardiac abnormalities. We present a new measure of Rd based on the root-mean
      square (RMS) curve of an ECG lead set and compare its performance with that of
      the commonly used QT dispersion (QTd) measure with the use of recovery times
      measured from directly recorded canine electrograms. METHODS AND RESULTS: Using
      isolated, perfused canine hearts suspended in a torso-shaped electrolytic tank,
      we simultaneously recorded electrograms from 64 epicardial sites and ECGs from
      192 "body surface" sites. RMS curves were derived from 4 lead sets: epicardial,
      body surface, precordial, and a 6-lead optimal set. Repolarization was altered by
      changing cycle length, temperature, and activation sequence. Rd, calculated
      directly from recovery times of the 64 epicardial potentials, was then compared
      with the width of the T wave of the RMS curve and with QTd for each of these 4
      lead sets. The correlation between T-wave width and Rd for each lead set,
      respectively, was epicardium, 0.91; body surface, 0.84; precordial, 0.72; and
      optimal leads, 0.81. The correlation between QTd and Rd for each lead set was
      epicardium, 0.46; body surface, 0.47; precordial, 0.17; and optimal leads, 0.11.
      CONCLUSIONS: RMS curve analysis provides an accurate method of estimating Rd from
      the body surface. In contrast, QTd analysis provides a poor estimate of Rd.

PMID- 10931811
TI  - G-Protein beta(3)-subunit 825T allele is associated with enhanced human atrial
      inward rectifier potassium currents.
AB  - BACKGROUND: A C825T polymorphism was recently identified in the human gene
      encoding for the beta(3)-subunit of heterotrimeric G proteins. The 825T allele is
      associated with a splice variant of Gbeta(3) and enhanced signal transduction. We
      hypothesized that patients carrying the 825T allele exhibit the modified Gbeta(3)
      phenotype. The resulting enhancement of signal transduction should be detectable
      in the Gbetagamma-dimer-mediated acetylcholine-stimulated K(+) current
      (I(K,ACh)). METHODS AND RESULTS: Seventy patients undergoing cardiac surgery were
      genotyped for the C825T polymorphism. In right atrial myocytes from these
      patients, the inward rectifier K(+) currents (I(K1), I(K,ACh)) were studied with
      the whole-cell patch-clamp technique. Background current I(K1) was measured with
      depolarizing ramp pulses and quantified as inward current at -100 mV; mean
      amplitudes were (pA/pF) 4.98+/-0.49 (n=30/93 patients/cells) in patients with CC
      genotype, 4.25+/-0.36 (n=31/121 patients/cells) with TC, and 7. 46+/-1.14 (n=9/32
      patients/cells; P<0.05) with TT. Conversely, mean I(K,ACh), which is maximally
      activated by carbachol (2 micromol/L), was reduced in patients with TT genotype
      (pA/pF, 4.30+/-1.33, n=9/27 patients/cells; P<0.05) compared with the other 2
      groups (6.56+/-0. 54, n=30/80 and 6.16+/-0.45, n=31/117 patients/cells, for CC
      and TC genotype, respectively). Essentially similar results were obtained with
      adenosine (1 mmol/L). CONCLUSIONS: We found an association between the Gbeta(3)
      825T allele and amplitude of human atrial I(K1) and I(K,ACh). Increased
      background current density in TT carriers could shorten action potential duration
      and may be due to I(K,ACh) being constitutively active in this genotype.

PMID- 10931812
TI  - Visualization and temporal/spatial characterization of cardiac radiofrequency
      ablation lesions using magnetic resonance imaging.
AB  - BACKGROUND: The purpose of this study was to describe a system and method for
      creating, visualizing, and monitoring cardiac radiofrequency ablation (RFA)
      therapy during magnetic resonance imaging (MRI). METHODS AND RESULTS: RFA was
      performed in the right ventricular apex of 6 healthy mongrel dogs with a custom
      7F nonmagnetic ablation catheter (4-mm electrode) in a newly developed real-time
      interactive cardiac MRI system. Catheters were positioned to intracardiac targets
      by use of an MRI fluoroscopy sequence, and ablated tissue was imaged with T2
      weighted fast spin-echo and contrast-enhanced T1-weighted gradient-echo
      sequences. Lesion size by MRI was determined and compared with measurements at
      gross and histopathological examination. Ablated areas of myocardium appeared as
      hyperintense regions directly adjacent to the catheter tip and could be detected
      2 minutes after RF delivery. Lesions reached maximum size approximately 5 minutes
      after ablation, whereas lesion signal intensity increased linearly with time but
      then reached a plateau at 12.2+/-2.1 minutes. Lesion size by MR correlated well
      with actual postmortem lesion size and histological necrosis area (55.4+/-7.2
      versus 49.7+/-5.9 mm(2), r=0.958, P<0.05). CONCLUSIONS: RFA can be performed in
      vivo in a new real-time interactive cardiac MRI system. The spatial and temporal
      extent of cardiac lesions can be visualized and monitored by T2- and T1-weighted
      imaging, and MRI lesion size agrees well with actual postmortem lesion size. MRI
      guided RFA may be a useful approach to help facilitate anatomic lesion placement
      and to provide insight into the biophysical effects of new ablation techniques
      and technologies.

PMID- 10931813
TI  - Effects of a K(+) channel opener to reduce transmural dispersion of
      repolarization and prevent torsade de pointes in LQT1, LQT2, and LQT3 models of
      the long-QT syndrome.
AB  - BACKGROUND: This study examines the effects of nicorandil, a K(+) channel opener,
      on transmural dispersion of repolarization (TDR) and induction of torsade de
      pointes (TdP) under conditions mimicking the LQT1, LQT2, and LQT3 forms of the
      congenital long-QT syndrome (LQTS). METHODS AND RESULTS: Transmembrane action
      potentials of epicardial, M, and endocardial cells were recorded simultaneously
      from an arterially perfused wedge of canine left ventricle together with a
      transmural ECG. Chromanol 293B (30 micromol/L) was used to block I(Ks) (LQT1
      model). Isoproterenol (50 to 100 nmol/L) was used to mimic an increase in beta
      adrenergic tone, d-sotalol (100 micromol/L) to block I(Kr) (LQT2 model), and ATX
      II (20 nmol/L) to augment late I(Na) (LQT3 model). Isoproterenol+chromanol 293B,
      d-sotalol, and ATX-II produced preferential prolongation of the action potential
      duration at 90% repolarization (APD(90)) of the M cell, an increase of TDR, and
      spontaneous as well as stimulation-induced TdP (LQT1, 3/6; LQT2, 3/6; LQT3, 5/6).
      Nicorandil (2 to 20 micromol/L) abbreviated the QT interval and APD(90) of the 3
      cell types in the 3 models. High concentrations (10 to 20 micromol/L) completely
      reversed the effects of 293B+/-isoproterenol and those of d-sotalol to increase
      APD(90) and TDR and to induce TdP in LQT1 and LQT2 models. Nicorandil 20
      micromol/L reversed only 50% of the effect of ATX-II and failed to completely
      suppress TdP in the LQT3 model (5/6 to 3/6). CONCLUSIONS: Our data suggest that
      K(+) channel openers may be capable of abbreviating the long QT interval,
      reducing TDR, and preventing spontaneous and stimulation-induced TdP when
      congenital or acquired LQTS is secondary to reduced I(Kr) or I(Ks) but less so
      when it is due to augmented late I(Na).

PMID- 10931814
TI  - Image in cardiovascular medicine. Myocardial infarction after dog bite.

PMID- 10931815
TI  - Concomitant endovascular repair of descending thoracic and abdominal aortic
      aneurysm.

PMID- 10931816
TI  - Nitric oxide synthesis and congestive heart failure.

PMID- 10931817
TI  - Tissue inhibition of angiotensin-converting enzyme activity stimulates
      angiogenesis in vivo: a potential downside.

PMID- 10931818
TI  - Diagnostic marker cooperative study for the diagnosis of myocardial infarction.

PMID- 10931819
TI  - Are all beta-blockers for heart failure the same?

PMID- 10931820
TI  - Effects of acute angiotensin II type 1 receptor antagonism and angiotensin
      converting enzyme inhibition on plasma fibrinolytic parameters in patients with
      heart failure.

PMID- 10931821
TI  - Diagnosing Alzheimer earlier.

PMID- 10931822
TI  - The calcineurin-binding protein cain is a negative regulator of synaptic vesicle
      endocytosis.
AB  - During neurotransmitter release, exocytosed neurotransmitter vesicles are
      recycled by endocytosis, which involves the assembly of a complex of endocytic
      proteins. Assembly of endocytic proteins into a functional complex depends on
      their dephosphorylation by calcineurin, a calcium-sensitive protein phosphatase
      and the inhibitory target of immunosuppressive drugs cyclosporin A and FK506.
      Cain is a recently identified protein inhibitor of calcineurin. We now provide
      evidence that cain is a component of the endocytic protein complex. The proline
      rich region of cain forms a stable association with the SH3 domain of amphiphysin
      1. Using a transferrin uptake assay, we found that overexpression of cain in
      HEK293 cells blocks endocytosis as potently as expression of a dominant negative
      dynamin 1 construct. The use of other calcineurin inhibitors such as cyclosporin
      A and FK506 also blocks endocytosis. Since binding of cain to amphiphysin 1 does
      not affect amphiphysin's interaction with other endocytic proteins, our results
      suggest that cain negatively regulates synaptic vesicle endocytosis by inhibiting
      calcineurin activity, rather than sterically interfering with the assembly of the
      endocytic protein complex.

PMID- 10931823
TI  - Characterization of the extra-large G protein alpha-subunit XLalphas. I. Tissue
      distribution and subcellular localization.
AB  - Our group previously described a new type of G protein, the 78-kDa XLalphas
      (extra large alphas) (Kehlenbach, R. H., Matthey, J., and Huttner, W. B. (1994)
      Nature 372, 804-809 and (1995) Nature 375, 253). Upon subcellular fractionation,
      XLalphas labeled by ADP-ribosylation with cholera toxin was previously mainly
      detected in the bottom fractions of a velocity sucrose gradient that contained
      trans-Golgi network and was differentially distributed to Galphas, which also
      peaked in the top fractions containing plasma membrane. Here, we investigate,
      using a new antibody specific for the XL domain, the tissue distribution and
      subcellular localization of XLalphas and novel splice variants referred to as
      XLN1. Upon immunoblotting and immunofluorescence analysis of various adult rat
      tissues, XLalphas and XLN1 were found to be enriched in neuroendocrine tissues,
      with a particularly high level of expression in the pituitary. By both
      immunofluorescence and immunogold electron microscopy, endogenous as well as
      transfected XLalphas and XLN1 were found to be predominantly associated with the
      plasma membrane, with only little immunoreactivity on internal, perinuclear
      membranes. Upon subcellular fractionation, immunoreactive XLalphas behaved
      similarly to Galphas but was differentially distributed to ADP-ribosylated
      XLalphas. Moreover, the bottom fractions of the velocity sucrose gradient were
      found to contain not only trans-Golgi network membranes but also certain
      subdomains of the plasma membrane, which reconciles the present with the previous
      observations. To further investigate the molecular basis of the association of
      XLalphas with the plasma membrane, chimeric proteins consisting of the XL domain
      or portions thereof fused to green fluorescent protein were analyzed by
      fluorescence and subcellular fractionation. In both neuroendocrine and non
      neuroendocrine cells, a fusion protein containing the entire XL domain, in
      contrast to one containing only the proline-rich and cysteine-rich regions, was
      exclusively localized at the plasma membrane. We conclude that the physiological
      role of XLalphas is at the plasma membrane, where it presumably is involved in
      signal transduction processes characteristic of neuroendocrine cells.

PMID- 10931824
TI  - Synergistic gene interactions control the induction of the mitochondrial
      uncoupling protein (Ucp1) gene in white fat tissue.
AB  - Among a selected group of mouse strains susceptible to dietary obesity, those
      with an enhanced capacity for Ucp1 and brown adipocyte induction in white fat
      preferentially lost body weight following adrenergic stimulation. Based on the
      generality of this mechanism for reducing obesity, a genetic analysis was
      initiated to identify genes that control brown adipocyte induction in white fat
      depots in mice. Quantitative trait locus (QTL) analysis was performed using the
      variations of retroperitoneal fat Ucp1 mRNA expression in progeny of genetic
      crosses between the A/J and C57BL/6J parental strains and selected AXB
      recombinant inbred strains. Three A/J-derived loci on chromosomes 2, 3, and 8 and
      one C57BL/6J locus on chromosome 19 were linked to Ucp1 induction in
      retroperitoneal fat. Although A/J-derived alleles seemed to contribute to
      elevated Ucp1 expression, the C57BL/6J allele on chromosome 19 increased Ucp1
      mRNA to levels higher than parental values. Thus, novel patterns of C57BL/6J and
      A/J recombinant genotypes among the four mapped loci resulted in a transgressive
      variation of Ucp1 phenotypes. Although the extent of the interchromosomal
      interactions have not been fully explored, strong synergistic interactions occur
      between a C57BL/6J allele on chromosome 19 and an A/J allele on chromosome 8. In
      addition to selective synergistic interactions between loci, variations in
      recessive and dominant effects also contribute to the final levels of Ucp1
      expression.

PMID- 10931825
TI  - Cell cycle-dependent coupling of the vasopressin V1a receptor to different G
      proteins.
AB  - Arginine vasopressin (AVP) regulates biological processes by binding to G protein
      coupled receptors. In Swiss 3T3 fibroblasts, expressing the V(1a) subtype of
      vasopressin receptors, AVP mobilizes calcium from intracellular stores. In
      proliferating cells, the AVP-induced increase in intracellular calcium
      concentration ([Ca(2+)](i)) was mediated by G proteins of the G(q) family, which
      are insensitive to pertussis toxin (PTX) pretreatment of the cells. In quiescent
      cells, the AVP-induced increase in [Ca(2+)](i) was partially PTX-sensitive,
      suggesting an involvement of G(i) proteins. We confirmed this by photoaffinity
      labeling of G proteins in Swiss 3T3 cell membranes activated by AVP. In Swiss 3T3
      cells arrested in the G(0)/G(1) phase of the cell cycle, the AVP-induced increase
      in [Ca(2+)](i) was also partially PTX-sensitive but was PTX-insensitive in cells
      arrested in other phases of the cell cycles. The blocking effect of PTX
      pretreatment in G(0)/G(1) cells was mimicked by microinjection of antisense
      oligonucleotides suppressing the expression of the Galpha(i3) subunits. These
      results were confirmed by microinjection of antibodies directed against the C
      terminus of G protein alpha-subunits. The data presented indicate that in Swiss
      3T3 fibroblasts synchronized in the G(0)/G(1) phase of the cell cycle the V(1a)
      receptor couples to G(q/11) and G(i3) to activate the phospholipase C-beta,
      leading to release of intracellular calcium.

PMID- 10931826
TI  - Identification of an aspartic residue in the P-loop of the vanilloid receptor
      that modulates pore properties.
AB  - Vanilloid receptor subunit 1 (VR1) is a nonselective cation channel that
      integrates multiple pain-producing stimuli. VR1 channels are blocked with high
      efficacy by the well established noncompetitive antagonist ruthenium red and
      exhibit high permeability to divalent cations. The molecular determinants that
      define these functional properties remain elusive. We have addressed this
      question and evaluated by site-specific neutralization the contribution on pore
      properties of acidic residues located in the putative VR1 pore region. Mutant
      receptors expressed in Xenopus oocytes exhibited capsaicin-operated ionic
      currents akin to those of wild type channels. Incorporation of glutamine residues
      at Glu(648) and Glu(651) rendered minor effects on VR1 pore attributes, while
      Glu(636) slightly modulated pore blockade. In contrast, replacement of Asp(646)
      by asparagine decreased 10-fold ruthenium red blockade efficacy and reduced 4
      fold the relative permeability of the divalent cation Mg(2+) with respect to
      Na(+) without changing the selectivity of monovalent cations. At variance with
      wild type channels and E636Q, E648Q, and E651Q mutant receptors, ruthenium red
      blockade of D646N mutants was weakly sensitive to extracellular pH acidification.
      Collectively, our results suggest that Asp(646) is a molecular determinant of VR1
      pore properties and imply that this residue may form a ring of negative charges
      that structures a high affinity binding site for cationic molecules at the
      extracellular entryway.

PMID- 10931827
TI  - beta-Adrenergic pathway induces apoptosis through calcineurin activation in
      cardiac myocytes.
AB  - Apoptosis of cardiac myocytes is one of the causes of heart failure. Here we
      examine the mechanism by which the activation of beta-adrenergic receptor induces
      cardiomyocyte apoptosis. Terminal deoxynucleotide transferase-mediated dUTP nick
      end labeling and DNA ladder analyses revealed that isoproterenol (Iso) induced
      the apoptosis of cardiac myocytes of neonatal rats through an increase in
      intracellular Ca(2+) levels. The Iso-induced cardiomyocyte apoptosis was strongly
      inhibited by the L-type Ca(2+) channel antagonist nifedipine and by the
      calcineurin inhibitors cyclosporin A and FK506. Iso reduced the phosphorylation
      levels of the proapoptotic Bcl-2 family protein Bad and induced cytochrome c
      release from mitochondria to the cytosol through calcineurin activation. Infusion
      of Iso increased calcineurin activity by approximately 3-fold in the hearts of
      wild-type mice but not in the hearts of transgenic mice that overexpress dominant
      negative mutants of calcineurin. Terminal deoxynucleotide transferase-mediated
      dUTP nick end labeling analysis revealed that infusion of Iso induced apoptosis
      of cardiac myocytes and that the number of apoptotic cardiomyocytes was
      significantly less in the hearts of the transgenic mice compared with the wild
      type mice. These results suggest that calcineurin plays a critical role in Iso
      induced apoptosis of cardiac myocytes, possibly through dephosphorylating Bad.

PMID- 10931828
TI  - ABC50 interacts with eukaryotic initiation factor 2 and associates with the
      ribosome in an ATP-dependent manner.
AB  - Eukaryotic initiation factor 2 (eIF2) plays a key role in the process of
      translation initiation and in its control. Here we demonstrate that highly
      purified mammalian eIF2 contains an additional polypeptide of apparent molecular
      mass of 110 kDa. This polypeptide co-purified with eIF2 through five different
      chromatography procedures. A cDNA clone encoding the polypeptide was isolated,
      and its sequence closely matched that of a protein previously termed ABC50, a
      member of the ATP-binding cassette (ABC) family of proteins. Antibodies to ABC50
      co-immunoprecipitated eIF2 and vice versa, indicating that the two proteins
      interact. The presence of ABC50 had no effect upon the ability of eIF2 to bind
      GDP but markedly enhanced the association of methionyl-tRNA with the factor.
      Unlike the majority of ABC proteins, which are membrane-associated transporters,
      ABC50 associates with the ribosome and co-sediments in sucrose gradients with the
      40 and 60 S ribosomal subunits. The association of ABC50 with ribosomal subunits
      was increased by ATP and decreased by ADP. ABC50 is related to GCN20 and eEF3,
      two yeast ABC proteins that are not membrane-associated transporters and are
      instead implicated in mRNA translation and/or its control. Thus, these data
      identify ABC50 as a third ABC protein with a likely function in mRNA translation,
      which associates with eIF2 and with ribosomes.

PMID- 10931829
TI  - The effects of changing the site of activating phosphorylation in CDK2 from
      threonine to serine.
AB  - Cyclin-dependent kinases (CDKs) that control cell cycle progression are regulated
      in many ways, including activating phosphorylation of a conserved threonine
      residue. This essential phosphorylation is carried out by the CDK-activating
      kinase (CAK). Here we examine the effects of replacing this threonine residue in
      human CDK2 by serine. We found that cyclin A bound equally well to wild-type CDK2
      (CDK2(Thr-160)) or to the mutant CDK2 (CDK2(Ser-160)). In the absence of
      activating phosphorylation, CDK2(Ser-160)-cyclin A complexes were more active
      than wild-type CDK2(Thr-160)-cyclin A complexes. In contrast, following
      activating phosphorylation, CDK2(Ser-160)-cyclin A complexes were less active
      than phosphorylated CDK2(Thr-160)-cyclin A complexes, reflecting a much smaller
      effect of activating phosphorylation on CDK2(Ser-160). The kinetic parameters for
      phosphorylating histone H1 were similar for mutant and wild-type CDK2, ruling out
      a general defect in catalytic activity. Interestingly, the CDK2(Ser-160) mutant
      was selectively defective in phosphorylating a peptide derived from the C
      terminal domain of RNA polymerase II. CDK2(Ser-160) was efficiently
      phosphorylated by CAKs, both human p40(MO15)(CDK7)-cyclin H and budding yeast
      Cak1p. In fact, the k(cat) values for phosphorylation of CDK2(Ser-160) were
      significantly higher than for phosphorylation of CDK2(Thr-160), indicating that
      CDK2(Ser-160) is actually phosphorylated more efficiently than wild-type CDK2. In
      contrast, dephosphorylation proceeded more slowly with CDK2(Ser-160) than with
      wild-type CDK2, either in HeLa cell extract or by purified PP2Cbeta. Combined
      with the more efficient phosphorylation of CDK2(Ser-160) by CAK, we suggest that
      one reason for the conservation of threonine as the site of activating
      phosphorylation may be to favor unphosphorylated CDKs following the degradation
      of cyclins.

PMID- 10931830
TI  - Cell type-specific regulation of B-Raf kinase by cAMP and 14-3-3 proteins.
AB  - Cyclic AMP can either activate or inhibit the mitogen-activated protein kinase
      (MAPK) pathway in different cell types; MAPK activation has been observed in B
      Raf-expressing cells and has been attributed to Rap1 activation with subsequent B
      Raf activation, whereas MAPK inhibition has been observed in cells lacking B-Raf
      and has been attributed to cAMP-dependent protein kinase (protein kinase A)
      mediated phosphorylation and inhibition of Raf-1 kinase. We found that cAMP
      stimulated MAPK activity in CHO-K1 and PC12 cells but inhibited MAPK activity in
      C6 and NB2A cells. In all four cell types, cAMP activated Rap1, and the 95- and
      68-kDa isoforms of B-Raf were expressed. cAMP activation or inhibition of MAPK
      correlated with activation or inhibition of endogenous and transfected B-Raf
      kinase. Although all cell types expressed similar amounts of 14-3-3 proteins,
      approximately 5-fold less 14-3-3 was associated with B-Raf in cells in which cAMP
      was inhibitory than in cells in which cAMP was stimulatory. We found that the
      cell type-specific inhibition of B-Raf could be completely prevented by
      overexpression of 14-3-3 isoforms, whereas expression of a dominant negative 14-3
      3 mutant resulted in partial loss of B-Raf activity. Our data suggest that 14-3-3
      bound to B-Raf protects the enzyme from protein kinase A-mediated inhibition; the
      amount of 14-3-3 associated with B-Raf may explain the tissue-specific effects of
      cAMP on B-Raf kinase activity.

PMID- 10931831
TI  - Inducible resistance to oxidant stress in the protozoan Leishmania chagasi.
AB  - Leishmania sp. protozoa are introduced into a mammalian skin by a sandfly vector,
      whereupon they encounter increased temperature and toxic oxidants generated
      during phagocytosis. We studied the effects of 37 degrees C "heat shock" or
      sublethal menadione, which generates superoxide and hydrogen peroxide, on
      Leishmania chagasi virulence. Both heat and menadione caused parasites to become
      more resistant to H(2)O(2)-mediated toxicity. Peroxide resistance was also
      induced as promastigotes developed in culture from logarithmic to their virulent
      stationary phase form. Peroxide resistance was not associated with an increase in
      reduced thiols (trypanothione and glutathione) or increased activity of ornithine
      decarboxylase, which is rate-limiting in trypanothione synthesis. Membrane
      lipophosphoglycan increased in size as parasites developed to stationary phase
      but not after environmental exposures. Instead, parasites underwent a heat shock
      response upon exposure to heat or sublethal menadione, detected by increased
      levels of HSP70. Transfection of promastigotes with L. chagasi HSP70 caused a
      heat-inducible increase in resistance to peroxide, implying it is involved in
      antioxidant defense. We conclude that leishmania have redundant mechanisms for
      resisting toxic oxidants. Some are induced during developmental change and others
      are induced in response to environmental stress.

PMID- 10931832
TI  - Biochemical characterization of the TATA-binding protein-Gal4 activation domain
      complex.
AB  - It has been suggested that complexes between gene-specific activators and the
      TATA-binding protein (TBP) play an important role in the expression of many
      genes. However, few detailed studies of well defined activator-TBP complexes have
      been reported. An analysis of the biochemical properties of the complex formed by
      the acidic activation domain (AAD) of the yeast activator Gal4 and TBP is
      presented here. This is shown to be composed of two AAD and one TBP molecule. DNA
      binding experiments reveal that TATA-containing DNAs and the Gal4 AAD bind TBP
      competitively, suggesting that the AAD and TATA boxes recognize overlapping
      surfaces of TBP. The kinetics of the formation and dissociation of the AAD(2)-TBP
      complex is also probed. The impact of these findings on models for Gal4-mediated
      transcriptional activation is considered.

PMID- 10931833
TI  - Synergistic action of hepatocyte nuclear factors 3 and 6 on CYP2C12 gene
      expression and suppression by growth hormone-activated STAT5b. Proposed model for
      female specific expression of CYP2C12 in adult rat liver.
AB  - Growth hormone (GH) exerts sexually dimorphic effects on liver gene transcription
      through its sex-dependent temporal pattern of pituitary hormone secretion.
      CYP2C12 encodes a female-specific rat liver P450 steroid hydroxylase whose
      expression is activated by continuous GH stimulation of hepatocytes. Presently,
      we investigated the role of liver-enriched and GH-regulated transcription factors
      in the activation of CYP2C12 gene expression in GH-stimulated liver cells.
      Transcription of a CYP2C12 promoter-luciferase reporter gene in transfected HepG2
      cells was activated 15-40-fold by the liver-enriched hepatocyte nuclear factor
      (HNF) 3 alpha, HNF3 beta, and HNF6. Synergistic interactions leading to an
      approximately 300-fold activation of the promoter by HNF3 beta in combination
      with HNF6 were observed. 5'-Deletion analysis localized the HNF6 response to a
      single 5'-proximal 96-nucleotide segment. By contrast, the stimulatory effects of
      HNF3 alpha and HNF3 beta were attributable to five distinct regions within the
      1.6-kilobase CYP2C12 proximal promoter. GH activation of the signal transducer
      and transcriptional activator STAT5b, which proceeds efficiently in male but not
      female rat liver, inhibited CYP2C12 promoter activation by HNF3 beta and HNF6,
      despite the absence of a classical STAT5-binding site. The female-specific
      pattern of CYP2C12 expression is thus proposed to reflect the positive
      synergistic action in female liver of liver-enriched and GH-regulated
      transcription factors, such as HNF3 beta and HNF6, coupled with a dominant
      inhibitory effect of GH-activated STAT5b that is manifest in males.

PMID- 10931834
TI  - NF-kappa B activity is required for the deregulation of c-myc expression by the
      immunoglobulin heavy chain enhancer.
AB  - The c-myc gene is translocated to one of the immunoglobulin genes in Burkitt's
      lymphoma resulting in deregulated expression of c-myc. Several enhancers have
      been shown to be important for expression of the immunoglobulin heavy chain gene.
      Four enhancer regions (murine-hypersensitive sites (MHS) 1, 2, 3, and 4) located
      3' of the murine immunoglobulin heavy chain gene play a role in activating
      expression of the translocated c-myc gene. The enhancer regions also result in a
      shift in transcriptional initiation from the P2 promoter to P1 that is
      characteristic of the translocated c-myc allele. We found that the most 3'
      enhancer region (MHS4) activated the c-myc promoter by 46-fold in the Raji
      Burkitt's lymphoma cell line, and it was the most active enhancer in these cells.
      The addition of enhancer regions MHS1,2 and 3 to MHS4 increased c-myc
      transcription by an additional 3-fold and resulted in the full promoter shift
      from P2 to P1. By deletion analysis of enhancer region MHS4, we located a region
      that was critical for the transcriptional activity of MHS4. Electrophoretic
      mobility shift assay analysis revealed that NF-kappaB/Rel family members bound to
      this region. Mutation of the NF-kappaB binding site abolished both the enhancer
      activity and the promoter shift activity of MHS4. An active NF-kappaB site was
      also identified in the human HS4 enhancer. Inhibition of c-myc promoter activity
      driven by the immunoglobulin enhancers was observed with expression of a super
      repressor IkappaBalpha construct. These results indicate that the NF-kappaB/Rel
      transcription factors play an important role in the deregulation of the
      translocated c-myc gene in Burkitt's lymphoma and suggest that interference with
      NF-kappaB function may represent a new approach to the treatment of Burkitt's
      lymphoma.

PMID- 10931835
TI  - WbpO, a UDP-N-acetyl-D-galactosamine dehydrogenase from Pseudomonas aeruginosa
      serotype O6.
AB  - WbpO is associated with B-band lipopolysaccharide biosynthesis in Pseudomonas
      aeruginosa serotype O6. This protein is thought to catalyze the enzymatic
      conversion of UDP-N-acetyl-d-galactosamine (UDP-GalNAc) to UDP-N-acetyl-d
      galactosaminuronic acid (UDP-GalNAcA). WbpO was overexpressed with a C-terminal
      hexahistidine tag. The soluble form of expressed WbpO (WbpO(Sol)) exhibited a
      secondary structure with 29.2% alpha-helix and 20.1% beta-strand. However, no
      enzymatic activity could be detected using either high performance anion exchange
      chromatography or capillary electrophoresis-mass spectrometry analysis. An
      insoluble form of expressed WbpO was purified in the presence of guanidine
      hydrochloride by immobilized metal ion affinity chromatography. After refolding,
      this preparation of WbpO (designated as WbpO(Rf)) exhibited stable secondary
      structure at pH 7.5 to 8.2, and it was enzymatically active. Capillary
      electrophoresis-mass spectrometry and tandem mass spectrometry analysis showed
      that WbpO(Rf) catalyzed the conversion of UDP-GalNAc to UDP-GalNAcA. 26 and 22%
      of the substrate could be converted to UDP-GalNAcA in the presence of NAD(+) and
      NADP(+) as the cofactors, respectively. The K(m) values of WbpO(Rf) for UDP
      GalNAc, NAD(+), and NADP(+) were 7.79, 0.65, and 0.44 mm, respectively. WbpO(Rf)
      can also catalyze the conversion of UDP-GlcNAc to UDP-GlcNAcA. In conclusion,
      this is the first report of the overexpression, purification, and biochemical
      characterization of an NAD(+)/NADP(+)-dependent UDP-GalNAc dehydrogenase. Our
      results also complete the biosynthetic pathway for GalNAcA that is part of the O
      antigen of P. aeruginosa serotype O6 lipopolysaccharide.

PMID- 10931836
TI  - Suppression of DNA repair by human T cell leukemia virus type 1 Tax is rescued by
      a functional p53 signaling pathway.
AB  - The Tax protein of human T cell leukemia virus type 1 is a viral transactivator
      and transforming protein. Tax is known to suppress cellular nucleotide excision
      repair (NER), and this activity has been proposed to play an important role in
      Tax transformation. In this study we have investigated the mechanism by which Tax
      suppresses NER with specific focus on the previously characterized ability of Tax
      to inhibit p53 function. Suppression of NER by Tax was rescued by overexpression
      of wild-type p53; however, a p53 transactivation-incompetent mutant did not
      restore NER activity. The cyclin-dependent kinase inhibitor p21, a major
      transcriptional target of p53, plays an important role in regulating DNA
      replication and repair. Overexpression of p21 reversed Tax-induced suppression of
      NER; however, a p21 C-terminal mutant that lacks the proliferating cell nuclear
      antigen binding domain did not restore NER activity. Thus, p53 and its downstream
      effector p21 can inhibit Tax-mediated suppression of DNA repair. These results
      imply that the inactivation of p53 function by Tax contributes to Tax suppression
      of DNA repair.

PMID- 10931837
TI  - The fate of membrane-bound ribosomes following the termination of protein
      synthesis.
AB  - Contemporary models for protein translocation in the mammalian endoplasmic
      reticulum (ER) identify the termination of protein synthesis as the signal for
      ribosome release from the ER membrane. We have utilized morphometric and
      biochemical methods to assess directly the fate of membrane-bound ribosomes
      following the termination of protein synthesis. In these studies, tissue culture
      cells were treated with cycloheximide to inhibit elongation, with pactamycin to
      inhibit initiation, or with puromycin to induce premature chain termination, and
      ribosome-membrane interactions were subsequently analyzed. It was found that
      following the termination of protein synthesis, the majority of ribosomal
      particles remained membrane-associated. Analysis of the subunit structure of the
      membrane-bound ribosomal particles remaining after termination was conducted by
      negative stain electron microscopy and sucrose gradient sedimentation. By both
      methods of analysis, the termination of protein synthesis on membrane-bound
      ribosomes was accompanied by the release of small ribosomal subunits from the ER
      membrane; the majority of the large subunits remained membrane-bound. On the
      basis of these results, we propose that large ribosomal subunit release from the
      ER membrane is regulated independently of protein translocation.

PMID- 10931838
TI  - Rabbit serum paraoxonase 3 (PON3) is a high density lipoprotein-associated
      lactonase and protects low density lipoprotein against oxidation.
AB  - The paraoxonase gene family contains at least three members: PON1, PON2, and
      PON3. The physiological roles of the corresponding gene products are still
      uncertain. Until recently, only the serum paraoxonase/arylesterase (PON1) had
      been purified and characterized. Here we report the purification, cloning, and
      characterization of rabbit serum PON3. PON3 is a 40-kDa protein associated with
      the high density lipoprotein fraction of serum. In contrast to PON1, PON3 has
      very limited arylesterase and no paraoxonase activities but rapidly hydrolyzes
      lactones such as statin prodrugs (e.g. lovastatin). These differences facilitated
      the complete separation of PON3 from PON1 during purification. PON3 hydrolyzes
      aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents
      but not simple lactones or those with polar substituents. We cloned PON3 from
      total rabbit liver RNA and expressed it in mammalian 293T/17 cells. The
      recombinant PON3 has the same apparent molecular mass and substrate specificity
      as the enzyme purified from serum. Rabbit serum PON3 is more efficient than
      rabbit PON1 in protecting low density lipoprotein from copper-induced oxidation.
      This is the first report that identifies a second PON enzyme in mammalian serum
      and the first to describe an enzymatic activity for PON3.

PMID- 10931839
TI  - Phosphorylation of Syk activation loop tyrosines is essential for Syk function.
      An in vivo study using a specific anti-Syk activation loop phosphotyrosine
      antibody.
AB  - Syk is an important protein-tyrosine kinase in immunoreceptor signaling.
      FcepsilonRI aggregation in mast cells induces tyrosine phosphorylation and
      increased enzymatic activity of Syk. The two adjacent tyrosines in the Syk
      activation loop are thought to be important for the propagation of FcepsilonRI
      signaling. To evaluate the phosphorylation of these tyrosines in vivo and further
      understand the relationship of Syk tyrosine phosphorylation with its function, an
      antibody was developed specific for phosphorylated tyrosines in the activation
      loop of Syk. FcepsilonRI aggregation on mast cells induced the phosphorylation of
      both tyrosine residues of the activation loop. The kinase activity of Syk played
      the major role in phosphorylating its activation loop tyrosines both in vivo and
      in vitro. In FcepsilonRI-stimulated mast cells, the total Syk tyrosine
      phosphorylation paralleled the phosphorylation of its activation loop tyrosines
      and downstream propagation of signals for histamine release. In contrast, the
      cell surface binding of anti-ganglioside monoclonal antibody AA4 induced only
      strong general tyrosine phosphorylation of Syk and minimal histamine release and
      weak phosphorylation of activation loop tyrosines. These results demonstrate that
      phosphorylation of the activation loop tyrosines is important for mediating
      receptor signaling and is a better marker of Syk function than is total Syk
      tyrosine phosphorylation.

PMID- 10931840
TI  - Synaptic localization and presynaptic function of calcium channel beta 4-subunits
      in cultured hippocampal neurons.
AB  - Neurotransmitter release is triggered by the influx of Ca(2+) into the
      presynaptic terminal through voltage gated Ca(2+)-channels. The shape of the
      presynaptic Ca(2+) signal largely determines the amount of released quanta and
      thus the size of the synaptic response. Ca(2+)-channel function is modulated in
      particular by the auxiliary beta-subunits that interact intracellularly with the
      pore-forming alpha(1)-subunit. Using retrovirus-mediated gene transfer in
      cultured hippocampal neurons, we demonstrate that functional GFP-beta(4)
      constructs colocalize with the synaptic vesicle marker synaptobrevin II and
      endogenous P/Q-type channels, indicating that beta(4)-subunits are localized to
      synaptic sites. Costaining with the dendritic marker MAP2 revealed that the
      beta(4)-subunit is transported to dendrites as well as axons. The nonconserved
      amino- and carboxyl-termini of the beta(4)-subunit were found to target the
      protein to the synapse. Physiological measurements in autaptic hippocampal
      neurons infected with green fluorescent protein (GFP)-beta(4) revealed an
      increase in both excitatory post-synaptic current amplitude and paired pulse
      facilitation ratio, whereas the GFP-beta(4) mutant, GFP-beta(4)(Delta50-407),
      which demonstrated a cytosolic localization pattern, did not alter these synaptic
      properties. In summary, our data suggest a pre-synaptic function of the Ca(2+)
      channel beta(4)-subunit in synaptic transmission.

PMID- 10931841
TI  - Direct examination of histone acetylation on Myc target genes using chromatin
      immunoprecipitation.
AB  - Overexpression of c-Myc can lead to altered transcriptional regulation of
      cellular genes and to neoplastic transformation. Although DNA binding is clearly
      required, the mechanism by which recruitment of c-Myc to target promoters results
      in transcriptional activation is highly debated. Much of this controversy comes
      from the difficulty in clearly defining a true Myc target gene. We have
      previously determined that cad is a bona fide Myc target gene and thus now use
      the cad promoter as a model to study Myc function. Others have shown that Myc can
      interact indirectly with histone acetylases and have suggested that Myc mediates
      transcriptional activation by causing an increase in the levels of acetylated
      histones on target promoters. To directly test this model, we employed a
      chromatin immunoprecipitation assay to examine the levels of acetylated histones
      on the cad promoter. Although Myc was bound to the cad promoter in S phase but
      not in G(0) phase, we found high levels of acetylated histones on the promoter in
      both stages. We also examined acetylated histones on the cad promoter before and
      after differentiation of U937 cells. Although the levels of c-Myc bound to the
      cad promoter were greatly reduced after differentiation, we saw high levels of
      acetylated histones on the cad promoter both before and after differentiation.
      Finally, we found that a 30-fold change in binding of N-Myc to the telomerase
      promoter did not result in a concomitant change in histone acetylation. Thus,
      recruitment of a Myc family member to a target promoter does not necessarily
      influence the amount of acetylated histones at that promoter. Further
      investigations are in progress to define the role of Myc in transcriptional
      activation.

PMID- 10931842
TI  - Cooperative interaction between HIV-1 regulatory proteins Tat and Vpr modulates
      transcription of the viral genome.
AB  - The virion-associated protein of human immunodeficiency virus, type 1 (HIV-1),
      Vpr, is a small protein with 96 amino acid residues that has the ability to
      modulate transcription of HIV-1 long terminal repeat (LTR) promoter activity and
      affects several cellular functions. In this study we have employed molecular
      approaches to further investigate the mechanism by which Vpr exerts its
      regulatory effect upon the LTR. We show that by structural and functional
      interaction with Tat, a potent viral regulatory protein, Vpr synergistically
      enhances the transcriptional activity of the HIV-1 LTR. Because Tat utilizes
      cyclin T1 and its partner, CDK9 to elevate the level of transcription from the
      LTR, we examined the cooperativity between Vpr, Tat, and cyclin T1/CDK9 on viral
      gene transcription. Results from co-transfection studies indicated
      superactivation of LTR by Tat and cyclin T1/CDK9 in the presence of wild type
      Vpr. This activation was not observed with the R73S mutant of Vpr, which contains
      arginine to serine transition at residue 73. Interestingly, expression of R73S
      mutant in cells exerts a negative effect on the observed superactivation of the
      LTR by Tat, cyclin T1/CDK9, and wild type Vpr. Results from protein-protein
      interaction studies indicated that Vpr is associated with both Tat and cyclin T1
      in cells expressing these proteins. Use of deletion mutant proteins in binding
      studies revealed that the binding sites for Tat and Vpr within cyclin T1 are
      distinct and that association of these two viral proteins with cyclin T1 is
      independent from each other. These observations suggest a working model on the
      cooperative interaction of Vpr with viral and cellular proteins and its
      involvement in control of viral gene transcription and replication. Moreover
      identification of R73S mutant of Vpr provides a new therapeutic avenue for
      controlling HIV-1 gene transcription and replication in the infected cells.

PMID- 10931843
TI  - Analysis of a Charcot-Marie-Tooth disease mutation reveals an essential internal
      ribosome entry site element in the connexin-32 gene.
AB  - A mutation located in the 5'-untranslated region (5'-UTR) of the nerve-specific
      connexin-32 mRNA, previously found in a family with Charcot-Marie-Tooth disease
      (CMTX), was analyzed for its effect on the expression of a reporter gene
      (luciferase) in transgenic mice and in transfected cells. Whereas both mutant and
      wild-type genes appeared to be transcribed and spliced efficiently, no luciferase
      was detected from the mutant in either system, suggesting that the mutation
      affects translation of the mRNA. When the 5'-UTR of nerve-specific connexin-32
      mRNA was inserted between the two genes of a bicistronic vector and transfected
      into various cell lines, expression of the second gene was significantly
      increased. Because the mutant did not facilitate translation of the second gene
      in the bicistronic mRNA system, this result suggested that the CMTX mutation
      abolished function of an internal ribosome entry site (IRES) in the 5'-UTR of the
      wild-type connexin-32 mRNA. The CMTX phenotype of the mutant 5'-UTR further
      suggested that the wild-type IRES was essential for the translation of the
      connexin-32 mRNA in nerve cells. In addition, other sequence elements of the
      connexin-32 IRES were characterized by mutation analysis. A mutation in either of
      the first two elements investigated showed loss of IRES function, whereas
      mutation of a third element showed gain of function.

PMID- 10931844
TI  - A regulatory role for ADP-ribosylation factor 6 (ARF6) in activation of the
      phagocyte NADPH oxidase.
AB  - In activated neutrophils NADPH oxidase is regulated through various signaling
      intermediates, including heterotrimeric G proteins, kinases, GTPases, and
      phospholipases. ADP-ribosylation factor (ARF) describes a family of GTPases
      associated with phospholipase D (PLD) activation. PLD is implicated in NADPH
      oxidase activation, although it is unclear whether activation of PLD by ARF is
      linked to receptor-mediated oxidase activation. We explored whether ARF
      participates in NADPH oxidase activation by formyl-methionine-leucine
      phenylalanine (fMLP) and whether this involves PLD. Using multicolor forward
      angle light scattering analyses to measure superoxide production in
      differentiated neutrophil-like PLB-985 cells, we tested enhanced green
      fluorescent fusion proteins of wild-type ARF1 or ARF6, or their mutant
      counterparts. The ARF6(Q67L) mutant defective in GTP hydrolysis caused increased
      superoxide production, whereas the ARF6(T27N) mutant defective in GTP binding
      caused diminished responses to fMLP. The ARF1 mutants had no effect on fMLP
      responses, and none of the ARF proteins affected phorbol 12-myristate 13-acetate
      elicited oxidase activity. PLD inhibitors 1-butanol and 2, 3-diphosphoglycerate,
      or the ARF6(N48R) mutant assumed to be defective in PLD activation, blocked fMLP
      elicited oxidase activity in transfected cells. The data suggest that ARF6 but
      not ARF1 modulates receptor-mediated NADPH oxidase activation in a PLD-dependent
      mechanism. Because PMA-elicited NADPH oxidase activation also appears to be PLD
      dependent, but ARF-independent, ARF6 and protein kinase C may act through
      distinct pathways, both involving PLD.

PMID- 10931845
TI  - The role of alpha,beta -dicarbonyl compounds in the toxicity of short chain
      sugars.
AB  - The extent to which sugars serve as targets for superoxide was examined using
      glycolaldehyde as the simplest sugar and using superoxide dismutase (SOD)-replete
      and SOD-null strains growing under aerobic and anaerobic conditions.
      Glycolaldehyde was more toxic to the SOD-null strain than to its SOD-replete
      parent, and this differential effect was oxygen-dependent. The product, glyoxal,
      could be trapped in the medium by 1,2-diaminobenzene and assayed as quinoxaline.
      The SOD-null strain produced more glyoxal and eliminated it more slowly than the
      SOD-replete parent strain. Glyoxal was approximately 10 times more toxic than
      glycolaldehyde and was more toxic to the SOD-null strain than to the parental
      strain. 1,2-Diaminobenzene protected against the toxicity of glycolaldehyde.
      These Escherichia coli strains contained the glutathione-dependent glyoxalases I
      and II, as well as the glutathione-independent glyoxalase III. Of these enzymes,
      glyoxalase III was most abundant, and it was inactivated within the aerobic SOD
      null strain and also in extracts when exposed to the flux of superoxide and
      hydrogen peroxide imposed by the xanthine oxidase reaction. Thus, it appears that
      short chain sugars are oxidized by superoxide yielding toxic dicarbonyls.
      Moreover, the defensive glyoxalase III is also inactivated by the oxidative
      stress imposed by the lack of SOD, thereby exacerbating the deleterious effect of
      sugar oxidation.

PMID- 10931847
TI  - An intronic downstream enhancer promotes 3' splice site usage of a neural cell
      specific exon.
AB  - The human nonmuscle myosin heavy chain B gene contains a 30-nucleotide
      alternative exon, N30, that is included in the mRNA from neural cells but is
      skipped in all other cells. We have previously identified an intronic distal
      downstream enhancer (IDDE) region that is required for neural cell-specific
      inclusion of N30. In this study, we investigated the mechanism by which the IDDE
      promotes N30 exon usage. In vitro splicing analysis using neural cell nuclear
      extracts and two-exon pre-mRNA substrates, which consist of the N30 exon and
      either the upstream (E5) or downstream (E6) exon, demonstrates that the IDDE
      activates upstream E5-N30 splicing by facilitating early prespliceosome complex
      formation. The IDDE has no effect on N30-E6 splicing where the IDDE resides.
      Inspection of splice site consensus sequences shows that a polypyrimidine (Py)
      tract preceding N30 is suboptimal for U2AF binding. Optimizing the Py tract
      completely relieves the requirement for the IDDE in E5-N30 splicing in vitro. In
      transfected cells, the wild-type minigene transcripts, which consist of three
      exons, E5, N30, and E6, undergo neural cell-specific and IDDE-dependent
      alternative splicing of N30. Optimizing the Py tract in minigenes also completely
      relieves the requirement for the IDDE in N30 inclusion. Furthermore,
      overexpression of the truncated U2AF65, which contains the arginine and serine
      dipeptide-rich domain and linker domain, but lacks the RNA binding domain,
      selectively inhibits the IDDE-mediated N30 inclusion in mRNA from the wild-type
      minigene in a dominant negative fashion. These results support the hypothesis
      that the IDDE facilitates the recognition of the 3' splice site preceding N30 by
      a network of protein-protein interactions implicated in the recruitment of U2AF
      to a suboptimal Py tract.

PMID- 10931846
TI  - Mechanism of pH-dependent N-acetylgalactosamine binding by a functional mimic of
      the hepatocyte asialoglycoprotein receptor.
AB  - Efficient release of ligands from the Ca(2+)-dependent carbohydrate-recognition
      domain (CRD) of the hepatic asialoglycoprotein receptor at endosomal pH requires
      a small set of conserved amino acids that includes a critical histidine residue.
      When these residues are incorporated at corresponding positions in an homologous
      galactose-binding derivative of serum mannose-binding protein, the pH dependence
      of ligand binding becomes more like that of the receptor. The modified CRD
      displays 40-fold preferential binding to N-acetylgalactosamine compared with
      galactose, making it a good functional mimic of the asialoglycoprotein receptor.
      In the crystal structure of the modified CRD bound to N-acetylgalactosamine, the
      histidine (His(202)) contacts the 2-acetamido methyl group and also participates
      in a network of interactions involving Asp(212), Arg(216), and Tyr(218) that
      positions a water molecule in a hydrogen bond with the sugar amide group. These
      interactions appear to produce the preference for N-acetylgalactosamine over
      galactose and are also likely to influence the pK(a) of His(202). Protonation of
      His(202) would disrupt its interaction with an asparagine that serves as a ligand
      for Ca(2+) and sugar. The structure of the modified CRD without sugar displays
      several different conformations that may represent structures of intermediates in
      the release of Ca(2+) and sugar ligands caused by protonation of His(202).

PMID- 10931848
TI  - Characterization of the chicken serotonin N-acetyltransferase gene. Activation
      via clock gene heterodimer/E box interaction.
AB  - The abundance of serotonin N-acetyltransferase (arylalkylamine N
      acetyltransferase, AANAT) mRNA in the chicken pineal gland exhibits a circadian
      rhythm, which is translated into a circadian rhythm in melatonin production. Here
      we have started to elucidate the molecular basis of the circadian rhythm in
      chicken AANAT (cAANAT). The 5'-flanking region of the cAANAT gene was isolated
      and found to contain an E box DNA element that confers strong luciferase reporter
      activity. In transfection experiments using chicken pineal cells, an E box
      mutation dramatically decreased reporter activity. Northern blot analysis
      indicated that several putative clock genes (bmal1, Clock, and MOP4) are co
      expressed in the chicken pineal gland. bmal1 mRNA is expressed in a rhythmic
      manner in the chicken pineal gland, with peak levels at early subjective night,
      coincident with the increase in cAANAT expression. Co-transfection experiments in
      COS cells demonstrated that chicken BMAL1/CLOCK and human BMAL1/MOP4 heterodimers
      bound the AANAT E box element and enhanced transcription. These observations
      suggest that binding of clock gene heterodimers to the cAANAT E box is a critical
      element in the expression of the cAANAT gene in vitro.

PMID- 10931849
TI  - Regulation of c-myc mRNA decay in vitro by a phorbol ester-inducible, ribosome
      associated component in differentiating megakaryoblasts.
AB  - The K562 leukemia cell line is bipotential for erythroid and megakaryoblastic
      differentiation. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA)
      activates a genetic program of gene expression in these cells leading to their
      differentiation into megakaryoblasts, a platelet precursor. Thus, K562 cells
      offer a means to examine early changes in gene expression necessary for
      megakaryoblastic commitment and differentiation. An essential requirement for
      differentiation of many hematopoietic cell types is the down-regulation of c-myc
      expression, because its constitutive expression blocks differentiation. TPA
      induced differentiation of K562 cells causes rapid down-regulation of c-myc
      expression, due in part to an mRNA decay rate that is 4-fold faster compared with
      dividing cells. A cell-free mRNA decay system reconstitutes TPA-induced
      destabilization of c-myc mRNA, but it requires at least two components for
      reconstitution. One component fractionates to the post-ribosomal supernatant from
      either untreated or treated cells. This component is sensitive to cycloheximide
      and micrococcal nuclease. The other component is polysome-associated and is
      induced or activated by TPA. Although in dividing cells c-myc mRNA decays via a
      sequential pathway involving removal of the poly(A) tract followed by degradation
      of the mRNA body, TPA activates a deadenylation-independent pathway. The cell
      free mRNA decay system reconstitutes this alternate decay pathway as well.

PMID- 10931850
TI  - PRMT3 is a distinct member of the protein arginine N-methyltransferase family.
      Conferral of substrate specificity by a zinc-finger domain.
AB  - S-Adenosyl-l-methionine-dependent protein arginine N-methyltransferases (PRMTs)
      catalyze the methylation of arginine residues within a variety of proteins. At
      least four distinct mammalian family members have now been described, including
      PRMT1, PRMT3, CARM1/PRMT4, and JBP1/PRMT5. To more fully define the physiological
      role of PRMT3, we characterized its unique putative zinc-finger domain and how it
      can affect its enzymatic activity. Here we show that PRMT3 does contain a single
      zinc-finger domain in its amino terminus. Although the zinc-liganded form of this
      domain is not required for methylation of an artificial substrate such as the
      glutathione S-transferase-fibrillarin amino-terminal fusion protein (GST-GAR), it
      is required for the enzyme to recognize RNA-associated substrates in RAT1 cell
      extracts. The recombinant form of PRMT3 is inhibited by high concentrations of
      ZnCl(2) as well as N-ethylmaleimide, reagents that can modify cysteine sulfhydryl
      groups. We found that we could distinguish PRMT family members by their
      sensitivity to these reagents; JBP1/PRMT5 and Hsl7 methyltransferases were
      inhibited in a similar manner as PRMT3, whereas Rmt1, PRMT1, and CARM1/PRMT4 were
      not affected. We were also able to define differences in these enzymes by their
      sensitivity to inhibition by Tris and free arginine. Finally, we found that the
      treatment of RAT1 cell extracts with N-ethylmaleimide leads to a loss of the
      major PRMT1-associated activity that was immune to inhibition under the same
      conditions as a GST fusion protein. These results suggest that native forms of
      PRMTs can have different properties than their GST-catalytic chain fusion protein
      counterparts, which may lack associated noncatalytic subunits.

PMID- 10931851
TI  - Characterization of the extra-large G protein alpha-subunit XLalphas. II. Signal
      transduction properties.
AB  - In the preceding paper (Pasolli, H. A., Klemke, M., Kehlenbach, R. H. , Wang, Y.,
      and Huttner, W. B. (2000) J. Biol. Chem. 275, 33622-33632), we report on the
      tissue distribution and subcellular localization of XLalphas (extra large
      alphas), a neuroendocrine-specific, plasma membrane-associated protein consisting
      of a novel 37-kDa XL domain followed by a 41-kDa alphas domain encoded by exons 2
      13 of the Galphas gene. Here, we have studied the signal transduction properties
      of XLalphas. Like Galphas, XLalphas undergoes a conformational change upon
      binding of GTPgammaS (guanosine 5'-O-(thio)triphosphate), as revealed by its
      partial resistance to tryptic digestion, which generated the same fragments as in
      the case of Galphas. Two approaches were used to analyze XLalphas-betagamma
      interactions: (i) ADP-ribosylation by cholera toxin to detect even weak or
      transient XLalphas-betagamma interactions and (ii) sucrose density gradient
      centrifugation to reveal stable heterotrimer formation. The addition of betagamma
      subunits resulted in an increased ADP-ribosylation of XLalphas as well as an
      increased sedimentation rate of XLalphas in sucrose density gradients, indicating
      that XLalphas interacts with the betagamma dimer. Surprisingly, however,
      XLalphas, in contrast to Galphas, was not activated by the beta2-adrenergic
      receptor upon reconstitution of S49cyc(-) membranes. Similarly, using
      photoaffinity labeling of pituitary membranes with azidoanilide-GTP, XLalphas was
      not activated upon stimulation of pituitary adenylyl cyclase-activating
      polypeptide (PACAP) receptors or other Galphas-coupled receptors known to be
      present in these membranes, whereas Galphas was. Despite the apparent inability
      of XLalphas to undergo receptor-mediated activation, XLalphas-GTPgammaS markedly
      stimulated adenylyl cyclase in S49cyc(-) membranes. Moreover, transfection of
      PC12 cells with a GTPase-deficient mutant of XLalphas, XLalphas-Q548L, resulted
      in a massive increase in adenylyl cyclase activity. Our results suggest that in
      neuroendocrine cells, the two related G proteins, Galphas and XLalphas, exhibit
      distinct properties with regard to receptor-mediated activation but converge onto
      the same effector system, adenylyl cyclase.

PMID- 10931852
TI  - Cloning, nucleotide sequence, and heterologous expression of the biosynthetic
      gene cluster for R1128, a non-steroidal estrogen receptor antagonist. Insights
      into an unusual priming mechanism.
AB  - R1128 substances are anthraquinone natural products that were previously reported
      as non-steroidal estrogen receptor antagonists with in vitro and in vivo potency
      approaching that of tamoxifen. From a biosynthetic viewpoint, these polyketides
      possess structurally interesting features such as an unusual primer unit that are
      absent in the well studied anthracyclic and tetracyclic natural products. The
      entire R1128 gene cluster was cloned and expressed in Streptomyces lividans, a
      genetically well developed heterologous host. In addition to R1128C, a novel
      optically active natural product, designated HU235, was isolated. Nucleotide
      sequence analysis of the biosynthetic gene cluster revealed genes encoding two
      ketosynthases, a chain length factor, an acyl transferase, three acetyl-CoA
      carboxylase subunits, two cyclases, two oxygenases, an amidase, and remarkably,
      two acyl carrier proteins. Feeding studies indicate that the unusual 4
      methylvaleryl side chain of R1128C is derived from valine. Together with the
      absence of a dedicated ketoreductase, dehydratase, or enoylreductase within the
      R1128 gene cluster, this suggests a functional link between fatty acid
      biosynthesis and R1128 biosynthesis in the engineered host. Specifically, we
      propose that the R1128 synthase recruits four subunits from the endogenous fatty
      acid synthase during the biosynthesis of this family of pharmacologically
      significant natural products.

PMID- 10931853
TI  - cAMP response element-binding protein-binding protein mediates thyrotropin
      releasing hormone signaling on thyrotropin subunit genes.
AB  - Transcription of pituitary alpha-glycoprotein hormone subunit (alpha-GSU) and
      thyrotropin beta subunit (TSH-beta) genes is stimulated by thyrotropin-releasing
      hormone (TRH). Since cAMP response element-binding protein (CREB)-binding protein
      (CBP) integrates a number of cell signaling pathways, we investigated whether CBP
      is important for TRH stimulation of the TSH subunit genes. Cotransfection of E1A
      in GH(3) cells completely blocked TRH stimulation of the TSH subunit genes,
      suggesting that CBP is a key factor for TRH signaling in the pituitary. CBP and
      Pit-1 acted synergistically in TRH stimulation of the TSH-beta promoter, and
      amino acids 1-450 of CBP were sufficient for the TRH effect. In contrast, on the
      human alpha-GSU promoter, CREB and P-Lim mediated TRH signaling. Intriguingly,
      CREB was phosphorylated upon TRH stimulation, leading to CBP recruitment to the
      alpha-GSU promoter. CBP also interacted with P-Lim in a TRH-dependent manner,
      suggesting that P-Lim is an important factor for non-cAMP response element
      mediated TRH stimulation of this promoter. Distinct domains of CBP were required
      for TRH signaling by CREB and P-Lim on the alpha-GSU promoter, amino acids 450
      700 and 1-450, respectively. Thus, the amino terminus of CBP plays a critical
      role in TRH signaling in the anterior pituitary via both Pit-1-dependent and 
      independent pathways, yielding differential regulation of pituitary gene
      products.

PMID- 10931855
TI  - Cell surface heparan sulfate proteoglycans: selective regulators of ligand
      receptor encounters.

PMID- 10931854
TI  - Oxygenation of the endocannabinoid, 2-arachidonylglycerol, to glyceryl
      prostaglandins by cyclooxygenase-2.
AB  - Cyclooxygenases (COX) play an important role in lipid signaling by oxygenating
      arachidonic acid to endoperoxide precursors of prostaglandins and thromboxane.
      Two cyclooxygenases exist which differ in tissue distribution and regulation but
      otherwise carry out identical chemical functions. The neutral arachidonate
      derivative, 2-arachidonylglycerol (2-AG), is one of two described
      endocannabinoids and appears to be a ligand for both the central (CB1) and
      peripheral (CB2) cannabinoid receptors. Here we report that 2-AG is a substrate
      for COX-2 and that it is metabolized as effectively as arachidonic acid. COX-2
      mediated 2-AG oxygenation provides the novel lipid, prostaglandin H(2) glycerol
      ester (PGH(2)-G), in vitro and in cultured macrophages. PGH(2)-G produced by
      macrophages is a substrate for cellular PGD synthase, affording PGD(2)-G.
      Pharmacological studies reveal that macrophage production of PGD(2)-G from
      endogenous sources of 2-AG is calcium-dependent and mediated by diacylglycerol
      lipase and COX-2. These results identify a distinct function for COX-2 in
      endocannabinoid metabolism and in the generation of a new family of
      prostaglandins derived from diacylglycerol and 2-AG.

PMID- 10931856
TI  - Identification and characterization of SA/Scc3p subunits in the Xenopus and human
      cohesin complexes.
AB  - A multisubunit protein complex, termed cohesin, plays an essential role in sister
      chromatid cohesion in yeast and in Xenopus laevis cell-free extracts. We report
      here that two distinct cohesin complexes exist in Xenopus egg extracts. A 14S
      complex (x-cohesin(SA1)) contains XSMC1, XSMC3, XRAD21, and a newly identified
      subunit, XSA1. In a second 12.5S complex (x-cohesin(SA2)), XSMC1, XSMC3, and
      XRAD21 associate with a different subunit, XSA2. Both XSA1 and XSA2 belong to the
      SA family of mammalian proteins and exhibit similarity to Scc3p, a recently
      identified component of yeast cohesin. In Xenopus egg extracts, x-cohesin(SA1) is
      predominant, whereas x-cohesin(SA2) constitutes only a very minor population.
      Human cells have a similar pair of cohesin complexes, but the SA2-type is the
      dominant form in somatic tissue culture cells. Immunolocalization experiments
      suggest that chromatin association of cohesin(SA1) and cohesin(SA2) may be
      differentially regulated. Dissociation of x-cohesin(SA1) from chromatin
      correlates with phosphorylation of XSA1 in the cell-free extracts. Purified cdc2
      cyclin B can phosphorylate XSA1 in vitro and reduce the ability of x-cohesin(SA1)
      to bind to DNA or chromatin. These results shed light on the mechanism by which
      sister chromatid cohesion is partially dissolved in early mitosis, far before the
      onset of anaphase, in vertebrate cells.

PMID- 10931858
TI  - The dynamics of postmitotic reassembly of the nucleolus.
AB  - Mammalian cell nucleoli disassemble at the onset of M-phase and reassemble during
      telophase. Recent studies showed that partially processed preribosomal RNA (pre
      rRNA) is preserved in association with processing components in the
      perichromosomal regions (PRs) and in particles called nucleolus-derived foci
      (NDF) during mitosis. Here, the dynamics of nucleolar reassembly were examined
      for the first time in living cells expressing fusions of the processing-related
      proteins fibrillarin, nucleolin, or B23 with green fluorescent protein (GFP).
      During telophase the NDF disappeared with a concomitant appearance of material in
      the reforming nuclei. Prenucleolar bodies (PNBs) appeared in nuclei in early
      telophase and gradually disappeared as nucleoli formed, strongly suggesting the
      transfer of PNB components to newly forming nucleoli. Fluorescence recovery after
      photobleaching (FRAP) showed that fibrillarin-GFP reassociates with the NDF and
      PNBs at rapid and similar rates. The reentry of processing complexes into
      telophase nuclei is suggested by the presence of pre-rRNA sequences in PNBs.
      Entry of specific proteins into the nucleolus approximately correlated with the
      timing of processing events. The mitotically preserved processing complexes may
      be essential for regulating the distribution of components to reassembling
      daughter cell nucleoli.

PMID- 10931859
TI  - Visualization of tRNA movements on the Escherichia coli 70S ribosome during the
      elongation cycle.
AB  - Three-dimensional cryomaps have been reconstructed for tRNA-ribosome complexes in
      pre- and posttranslocational states at 17-A resolution. The positions of tRNAs in
      the A and P sites in the pretranslocational complexes and in the P and E sites in
      the posttranslocational complexes have been determined. Of these, the P-site tRNA
      position is the same as seen earlier in the initiation-like fMet-tRNA(f)(Met)
      ribosome complex, where it was visualized with high accuracy. Now, the positions
      of the A- and E-site tRNAs are determined with similar accuracy. The positions of
      the CCA end of the tRNAs at the A site are different before and after peptide
      bond formation. The relative positions of anticodons of P- and E-site tRNAs in
      the posttranslocational state are such that a codon-anticodon interaction at the
      E site appears feasible.

PMID- 10931857
TI  - Tracking COL1A1 RNA in osteogenesis imperfecta. splice-defective transcripts
      initiate transport from the gene but are retained within the SC35 domain.
AB  - This study illuminates the intra-nuclear fate of COL1A1 RNA in osteogenesis
      imperfecta (OI) Type I. Patient fibroblasts were shown to carry a heterozygous
      defect in splicing of intron 26, blocking mRNA export. Both the normal and mutant
      allele associated with a nuclear RNA track, a localized accumulation of
      posttranscriptional RNA emanating to one side of the gene. Both tracks had
      slightly elongated or globular morphology, but mutant tracks were cytologically
      distinct in that they lacked the normal polar distribution of intron 26. Normal
      COL1A1 RNA tracks distribute throughout an SC-35 domain, from the gene at the
      periphery. Normally, almost all 50 COL1A1 introns are spliced at or adjacent to
      the gene, before mRNA transits thru the domain. Normal COL1A1 transcripts may
      undergo maturation needed for export within the domain such as removal of a slow
      splicing intron (shown for intron 24), after which they may disperse. Splice
      defective transcripts still distribute thru the SC-35 domain, moving
      approximately 1-3 micrometer from the gene. However, microfluorimetric analyses
      demonstrate mutant transcripts accumulate to abnormal levels within the track and
      domain. Hence, mutant transcripts initiate transport from the gene, but are
      impeded in exit from the SC-35 domain. This identifies a previously undefined
      step in mRNA export, involving movement through an SC-35 domain. A model is
      presented in which maturation and release for export of COL1A1 mRNA is linked to
      rapid cycling of metabolic complexes within the splicing factor domain, adjacent
      to the gene. This paradigm may apply to SC-35 domains more generally, which we
      suggest may be nucleated at sites of high demand and comprise factors being
      actively used to facilitate expression of associated loci.

PMID- 10931860
TI  - Mutants affecting the structure of the cortical endoplasmic reticulum in
      Saccharomyces cerevisiae.
AB  - We find that the peripheral ER in Saccharomyces cerevisiae forms a dynamic
      network of interconnecting membrane tubules throughout the cell cycle, similar to
      the ER in higher eukaryotes. Maintenance of this network does not require
      microtubule or actin filaments, but its dynamic behavior is largely dependent on
      the actin cytoskeleton. We isolated three conditional mutants that disrupt
      peripheral ER structure. One has a mutation in a component of the COPI coat
      complex, which is required for vesicle budding. This mutant has a partial defect
      in ER segregation into daughter cells and disorganized ER in mother cells. A
      similar phenotype was found in other mutants with defects in vesicular
      trafficking between ER and Golgi complex, but not in mutants blocked at later
      steps in the secretory pathway. The other two mutants found in the screen have
      defects in the signal recognition particle (SRP) receptor. This receptor, along
      with SRP, targets ribosome-nascent chain complexes to the ER membrane for protein
      translocation. A conditional mutation in SRP also disrupts ER structure, but
      other mutants with translocation defects do not. We also demonstrate that, both
      in wild-type and mutant cells, the ER and mitochondria partially coalign, and
      that mutations that disrupt ER structure also affect mitochondrial structure. Our
      data suggest that both trafficking between the ER and Golgi complex and ribosome
      targeting are important for maintaining ER structure, and that proper ER
      structure may be required to maintain mitochondrial structure.

PMID- 10931861
TI  - Phosphorylation of the vesicle-tethering protein p115 by a casein kinase II-like
      enzyme is required for Golgi reassembly from isolated mitotic fragments.
AB  - Coat protein I (COPI) transport vesicles can be tethered to Golgi membranes by a
      complex of fibrous, coiled-coil proteins comprising p115, Giantin and GM130. p115
      has been postulated to act as a bridge, linking Giantin on the vesicle to GM130
      on the Golgi membrane. Here we show that the acidic COOH terminus of p115
      mediates binding to both GM130 and Giantin as well as linking the two together.
      Phosphorylation of serine 941 within this acidic domain enhances the binding as
      well as the link between them. Phosphorylation is mediated by casein kinase II
      (CKII) or a CKII-like kinase. Surprisingly, the highly conserved NH(2)-terminal
      head domain of p115 is not required for the NSF (N-ethylmaleimide-sensitive
      fusion protein)-catalyzed reassembly of cisternae from mitotic Golgi fragments in
      a cell-free system. However, the ability of p115 to link GM130 to Giantin and the
      phosphorylation of p115 at serine 941 are required for NSF-catalyzed cisternal
      regrowth. p115 phosphorylation may be required for the transition from COPI
      vesicle tethering to COPI vesicle docking, an event that involves the formation
      of trans-SNARE [corrected] (trans-soluble NSF attachment protein [SNAP] receptor)
      complexes.

PMID- 10931862
TI  - Pex11p plays a primary role in medium-chain fatty acid oxidation, a process that
      affects peroxisome number and size in Saccharomyces cerevisiae.
AB  - The Saccharomyces cerevisiae peroxisomal membrane protein Pex11p has previously
      been implicated in peroxisome proliferation based on morphological observations
      of PEX11 mutant cells. Pex11p-deficient cells fail to increase peroxisome number
      in response to growth on fatty acids and instead accumulate a few giant
      peroxisomes. We report that mutants deficient in genes required for medium-chain
      fatty acid (MCFA) beta-oxidation display the same phenotype as Pex11p-deficient
      cells. Upon closer inspection, we found that Pex11p is required for MCFA beta
      oxidation. Disruption of the PEX11 gene results in impaired formation of MCFA-CoA
      esters as measured in intact cells, whereas their formation is normal in cell
      lysates. The sole S. cerevisiae MCFA-CoA synthetase (Faa2p) remains properly
      localized to the inner leaflet of the peroxisomal membrane in PEX11 mutant cells.
      Therefore, the in vivo latency of MCFA activation observed in Pex11p-deficient
      cells suggests that Pex11p provides Faa2p with substrate. When PEX11 mutant cells
      are shifted from glucose to oleate-containing medium, we observed an immediate
      deficiency in beta-oxidation of MCFAs whereas giant peroxisomes and a failure to
      increase peroxisome abundance only became apparent much later. Our observations
      suggest that the MCFA oxidation pathway regulates the level of a signaling
      molecule that modulates the number of peroxisomal structures in a cell.

PMID- 10931863
TI  - A kinesin-related protein, KRP(180), positions prometaphase spindle poles during
      early sea urchin embryonic cell division.
AB  - We have investigated the intracellular roles of an Xklp2-related kinesin motor,
      KRP(180), in positioning spindle poles during early sea urchin embryonic cell
      division using quantitative, real-time analysis. Immunolocalization reveals that
      KRP(180) concentrates on microtubules in the central spindle, but is absent from
      centrosomes. Microinjection of inhibitory antibodies and dominant negative
      constructs suggest that KRP(180) is not required for the initial separation of
      spindle poles, but instead functions to transiently position spindle poles
      specifically during prometaphase.

PMID- 10931864
TI  - Two distinct regions in a yeast myosin-V tail domain are required for the
      movement of different cargoes.
AB  - The Saccharomyces cerevisiae myosin-V, Myo2p, is essential for polarized growth,
      most likely through transport of secretory vesicles to the developing bud. Myo2p
      is also required for vacuole movement, a process not essential for growth. The
      globular region of the myosin-V COOH-terminal tail domain is proposed to bind
      cargo. Through random mutagenesis of this globular tail, we isolated six new
      single point mutants defective in vacuole inheritance, but not polarized growth.
      These point mutations cluster to four amino acids in an 11-amino acid span,
      suggesting that this region is important for vacuole movement. In addition,
      through characterization of myo2-DeltaAflII, a deletion of amino acids 1,459
      1,491, we identified a second region of the globular tail specifically required
      for polarized growth. Whereas this mutant does not support growth, it complements
      the vacuole inheritance defect in myo2-2 (G1248D) cells. Moreover, overexpression
      of the myo2-DeltaAflII globular tail interferes with vacuole movement, but not
      polarized growth. These data indicate that this second region is dispensable for
      vacuole movement. The identification of these distinct subdomains in the cargo
      binding domain suggests how myosin-Vs can move multiple cargoes. Moreover, these
      studies suggest that the vacuole receptor for Myo2p differs from the receptor for
      the essential cargo.

PMID- 10931865
TI  - Three regions within ActA promote Arp2/3 complex-mediated actin nucleation and
      Listeria monocytogenes motility.
AB  - The Listeria monocytogenes ActA protein induces actin-based motility by enhancing
      the actin nucleating activity of the host Arp2/3 complex. Using systematic
      truncation analysis, we identified a 136-residue NH(2)-terminal fragment that was
      fully active in stimulating nucleation in vitro. Further deletion analysis
      demonstrated that this fragment contains three regions, which are important for
      nucleation and share functional and/or limited sequence similarity with host WASP
      family proteins: an acidic stretch, an actin monomer-binding region, and a
      cofilin homology sequence. To determine the contribution of each region to actin
      based motility, we compared the biochemical activities of ActA derivatives with
      the phenotypes of corresponding mutant bacteria in cells. The acidic stretch
      functions to increase the efficiency of actin nucleation, the rate and frequency
      of motility, and the effectiveness of cell-cell spread. The monomer-binding
      region is required for actin nucleation in vitro, but not for actin
      polymerization or motility in infected cells, suggesting that redundant
      mechanisms may exist to recruit monomer in host cytosol. The cofilin homology
      sequence is critical for stimulating actin nucleation with the Arp2/3 complex in
      vitro, and is essential for actin polymerization and motility in cells. These
      data demonstrate that each region contributes to actin-based motility, and that
      the cofilin homology sequence plays a principal role in activation of the Arp2/3
      complex, and is an essential determinant of L. monocytogenes pathogenesis.

PMID- 10931866
TI  - Functional analysis of a human homologue of the Drosophila actin binding protein
      anillin suggests a role in cytokinesis.
AB  - We have characterized a human homologue of anillin, a Drosophila actin binding
      protein. Like Drosophila anillin, the human protein localizes to the nucleus
      during interphase, the cortex following nuclear envelope breakdown, and the
      cleavage furrow during cytokinesis. Anillin also localizes to ectopic cleavage
      furrows generated between two spindles in fused PtK(1) cells. Microinjection of
      antianillin antibodies slows cleavage, leading to furrow regression and the
      generation of multinucleate cells. GFP fusions that contain the COOH-terminal 197
      amino acids of anillin, which includes a pleckstrin homology (PH) domain, form
      ectopic cortical foci during interphase. The septin Hcdc10 localizes to these
      ectopic foci, whereas myosin II and actin do not, suggesting that anillin
      interacts with the septins at the cortex. Robust cleavage furrow localization
      requires both this COOH-terminal domain and additional NH(2)-terminal sequences
      corresponding to an actin binding domain defined by in vitro cosedimentation
      assays. Endogenous anillin and Hcdc10 colocalize to punctate foci associated with
      actin cables throughout mitosis and the accumulation of both proteins at the cell
      equator requires filamentous actin. These results indicate that anillin is a
      conserved cleavage furrow component important for cytokinesis. Interactions with
      at least two other furrow proteins, actin and the septins, likely contribute to
      anillin function.

PMID- 10931867
TI  - Distinct families of Z-line targeting modules in the COOH-terminal region of
      nebulin.
AB  - To learn how nebulin functions in the assembly and maintenance of I-Z-I bands,
      MYC- and GFP- tagged nebulin fragments were expressed in primary cultured
      skeletal myotubes. Their sites of incorporation were visualized by double
      staining with anti-MYC, antibodies to myofibrillar proteins, and FITC- or
      rhodamine phalloidin. Contrary to expectations based on in vitro binding studies,
      none of the nebulin fragments expressed in maturing myotubes were incorporated
      selectively into I-band approximately 1.0-micrometer F-alpha-actin-containing
      thin filaments. Four of the MYC/COOH-terminal nebulin fragments were incorporated
      exclusively into periodic approximately 0.1-micrometer Z-bands. Whereas both anti
      MYC and Rho-phalloidin stained intra-Z-band F-alpha-actin oligomers, only the
      latter stained the pointed ends of the polarized approximately 1.0-micrometer
      thin filaments. Z-band incorporation was independent of the nebulin COOH-terminal
      Ser or SH3 domains. In vitro cosedimentation studies also demonstrated that
      nebulin SH3 fragments did not bind to F-alpha-actin or alpha-actinin. The
      remaining six fragments were not incorporated into Z-bands, but were incorporated
      (a) diffusely throughout the sarcoplasm and into (b) fibrils/patches of varying
      lengths and widths nested among normal striated myofibrils. Over time, presumably
      in response to the mediation of muscle-specific homeostatic controls, many of the
      ectopic MYC-positive structures were resorbed. None of the tagged nebulin
      fragments behaved as dominant negatives; they neither blocked the assembly nor
      induced the disassembly of mature striated myofibrils. Moreover, they were not
      cytotoxic in myotubes, as they were in the fibroblasts and presumptive myoblasts
      in the same cultures.

PMID- 10931869
TI  - Nicotinic acid adenine dinucleotide phosphate (NAADP(+)) is an essential
      regulator of T-lymphocyte Ca(2+)-signaling.
AB  - Microinjection of human Jurkat T-lymphocytes with nicotinic acid adenine
      dinucleotide phosphate (NAADP(+)) dose-dependently stimulated intracellular
      Ca(2+)-signaling. At a concentration of 10 nM NAADP(+) evoked repetitive and long
      lasting Ca(2+)-oscillations of low amplitude, whereas at 50 and 100 nM, a rapid
      and high initial Ca(2+)-peak followed by trains of smaller Ca(2+)-oscillations
      was observed. Higher concentrations of NAADP(+) (1 and 10 microM) gradually
      reduced the initial Ca(2+)-peak, and a complete self-inactivation of Ca(2+)
      signals was seen at 100 microM. The effect of NAADP(+) was specific as it was not
      observed with nicotinamide adenine dinucleotide phosphate. Both inositol 1,4, 5
      trisphosphate- and cyclic adenosine diphosphoribose-mediated Ca(2+)-signaling
      were efficiently inhibited by coinjection of a self-inactivating concentration of
      NAADP(+). Most importantly, microinjection of a self-inactivating concentration
      of NAADP(+) completely abolished subsequent stimulation of Ca(2+)-signaling via
      the T cell receptor/CD3 complex, indicating that a functional NAADP(+) Ca(2+)
      release system is essential for T-lymphocyte Ca(2+)-signaling.

PMID- 10931868
TI  - p120 catenin regulates the actin cytoskeleton via Rho family GTPases.
AB  - Cadherins are calcium-dependent adhesion molecules responsible for the
      establishment of tight cell-cell contacts. p120 catenin (p120ctn) binds to the
      cytoplasmic domain of cadherins in the juxtamembrane region, which has been
      implicated in regulating cell motility. It has previously been shown that
      overexpression of p120ctn induces a dendritic morphology in fibroblasts
      (Reynolds, A.B. , J. Daniel, Y. Mo, J. Wu, and Z. Zhang. 1996. Exp. Cell Res.
      225:328-337.). We show here that this phenotype is suppressed by coexpression of
      cadherin constructs that contain the juxtamembrane region, but not by constructs
      lacking this domain. Overexpression of p120ctn disrupts stress fibers and focal
      adhesions and results in a decrease in RhoA activity. The p120ctn-induced
      phenotype is blocked by dominant negative Cdc42 and Rac1 and by constitutively
      active Rho-kinase, but is enhanced by dominant negative RhoA. p120ctn
      overexpression increased the activity of endogenous Cdc42 and Rac1. Exploring how
      p120ctn may regulate Rho family GTPases, we find that p120ctn binds the Rho
      family exchange factor Vav2. The behavior of p120ctn suggests that it is a
      vehicle for cross-talk between cell-cell junctions and the motile machinery of
      cells. We propose a model in which p120ctn can shuttle between a cadherin-bound
      state and a cytoplasmic pool in which it can interact with regulators of Rho
      family GTPases. Factors that perturb cell-cell junctions, such that the
      cytoplasmic pool of p120ctn is increased, are predicted to decrease RhoA activity
      but to elevate active Rac1 and Cdc42, thereby promoting cell migration.

PMID- 10931871
TI  - Rabies virus-induced membrane fusion pathway.
AB  - Fusion of rabies virus with membranes is triggered at low pH and is mediated by
      the viral glycoprotein (G). The rabies virus-induced fusion pathway was studied
      by investigating the effects of exogenous lipids having various dynamic molecular
      shapes on the fusion process. Inverted cone-shaped lysophosphatidylcholines
      (LPCs) blocked fusion at a stage subsequent to fusion peptide insertion into the
      target membrane. Consistent with the stalk-hypothesis, LPC with shorter alkyl
      chains inhibited fusion at lower membrane concentrations and this inhibition was
      compensated by the presence of oleic acid. However, under suboptimal fusion
      conditions, short chain LPCs, which were translocated in the inner leaflet of the
      membranes, considerably reduced the lag time preceding membrane merging,
      resulting in faster kinetics of fusion. This indicated that the rate limiting
      step for fusion is the formation of a fusion pore in a diaphragm of restricted
      hemifusion. The previously described cold-stabilized prefusion complex was also
      characterized. This intermediate is at a well-advanced stage of the fusion
      process when the hemifusion diaphragm is destabilized, but lipid mixing is still
      restricted, probably by a ring-like complex of glycoproteins. I provide evidence
      that this state has a dynamic character and that its lipid organization can
      reverse back to two lipid bilayers.

PMID- 10931870
TI  - Mutations in synaptojanin disrupt synaptic vesicle recycling.
AB  - Synaptojanin is a polyphosphoinositide phosphatase that is found at synapses and
      binds to proteins implicated in endocytosis. For these reasons, it has been
      proposed that synaptojanin is involved in the recycling of synaptic vesicles.
      Here, we demonstrate that the unc-26 gene encodes the Caenorhabditis elegans
      ortholog of synaptojanin. unc-26 mutants exhibit defects in vesicle trafficking
      in several tissues, but most defects are found at synaptic termini. Specifically,
      we observed defects in the budding of synaptic vesicles from the plasma membrane,
      in the uncoating of vesicles after fission, in the recovery of vesicles from
      endosomes, and in the tethering of vesicles to the cytoskeleton. Thus, these
      results confirm studies of the mouse synaptojanin 1 mutants, which exhibit
      defects in the uncoating of synaptic vesicles (Cremona, O., G. Di Paolo, M.R.
      Wenk, A. Luthi, W.T. Kim, K. Takei, L. Daniell, Y. Nemoto, S.B. Shears, R.A.
      Flavell, D.A. McCormick, and P. De Camilli. 1999. Cell. 99:179-188), and further
      demonstrate that synaptojanin facilitates multiple steps of synaptic vesicle
      recycling.

PMID- 10931872
TI  - The specificity for the differentiation blocking activity of carcinoembryonic
      antigen resides in its glycophosphatidyl-inositol anchor.
AB  - Ectopic expression of various members of the human carcinoembryonic antigen (CEA)
      family of intercellular adhesion molecules in murine myoblasts either blocks
      (CEA, CEACAM6) or allows (CEACAM1) myogenic differentiation. These surface
      glycoproteins form a subset of the immunoglobulin (Ig) superfamily and are very
      closely related, but differ in the precise sequence of their external domains and
      in their mode of anchorage to the cell membrane. CEA and CEACAM6 are
      glycophosphatidyl-inositol (GPI) anchored, whereas CEACAM1 is transmembrane (TM)
      anchored. Overexpression of GPI-linked neural cell adhesion molecule (NCAM) p125,
      also an adhesion molecule of the Ig superfamily, accelerates myogenic
      differentiation. The molecular requirements for the myogenic differentiation
      block were investigated using chimeric constructs in which the COOH-terminal
      hydrophobic domains of CEA, CEACAM1, and NCAM p125 were exchanged. The presence
      of the GPI signal sequence specifically from CEA in the chimeras was sufficient
      to convert both CEACAM1 and NCAM into differentiation-blocking proteins.
      Conversely, CEA could be converted into a neutral protein by exchanging its GPI
      anchor for the TM anchor of CEACAM1. Since the external domains of CEA, CEACAM1,
      and NCAM can all undergo homophilic interactions, and mutations in the self
      adhesive domains of CEA abrogate its differentiation-blocking activity, the
      structural requirements for differentiation-inhibition are any self-adhesive
      domains attached to the specific GPI anchor derived from CEA. We therefore
      suggest that biologically significant functional information resides in the
      processed extreme COOH terminus of CEA and in the GPI anchor that it determines.

PMID- 10931873
TI  - Restructuring of focal adhesion plaques by PI 3-kinase. Regulation by PtdIns
      (3,4,5)-p(3) binding to alpha-actinin.
AB  - Focal adhesions are an elaborate network of interconnecting proteins linking
      actin stress fibers to the extracellular matrix substrate. Modulation of the
      focal adhesion plaque provides a mechanism for the regulation of cellular
      adhesive strength. Using interference reflection microscopy, we found that
      activation of phosphoinositide 3-kinase (PI 3-kinase) by PDGF induces the
      dissipation of focal adhesions. Loss of this close apposition between the cell
      membrane and the extracellular matrix coincided with a redistribution of alpha
      actinin and vinculin from the focal adhesion complex to the Triton X-100-soluble
      fraction. In contrast, talin and paxillin remained localized to focal adhesions,
      suggesting that activation of PI 3-kinase induced a restructuring of the plaque
      rather than complete dispersion. Furthermore, phosphatidylinositol (3,4, 5)
      trisphosphate (PtdIns (3,4,5)-P(3)), a lipid product of PI 3-kinase, was
      sufficient to induce restructuring of the focal adhesion plaque. We also found
      that PtdIns (3,4,5)-P(3) binds to alpha-actinin in PDGF-treated cells. Further
      evidence demonstrated that activation of PI 3-kinase by PDGF induced a decrease
      in the association of alpha-actinin with the integrin beta subunit, and that
      PtdIns (3,4,5)-P(3) could disrupt this interaction in vitro. Modification of
      focal adhesion structure by PI 3-kinase and its lipid product, PtdIns (3,4,5)
      P(3), has important implications for the regulation of cellular adhesive strength
      and motility.

PMID- 10931874
TI  - Characterization of palladin, a novel protein localized to stress fibers and cell
      adhesions.
AB  - Here, we describe the identification of a novel phosphoprotein named palladin,
      which colocalizes with alpha-actinin in the stress fibers, focal adhesions, cell
      cell junctions, and embryonic Z-lines. Palladin is expressed as a 90-92-kD
      doublet in fibroblasts and coimmunoprecipitates in a complex with alpha-actinin
      in fibroblast lysates. A cDNA encoding palladin was isolated by screening a mouse
      embryo library with mAbs. Palladin has a proline-rich region in the NH(2)
      terminal half of the molecule and three tandem Ig C2 domains in the COOH-terminal
      half. In Northern and Western blots of chick and mouse tissues, multiple isoforms
      of palladin were detected. Palladin expression is ubiquitous in embryonic
      tissues, and is downregulated in certain adult tissues in the mouse. To probe the
      function of palladin in cultured cells, the Rcho-1 trophoblast model was used.
      Palladin expression was observed to increase in Rcho-1 cells when they began to
      assemble stress fibers. Antisense constructs were used to attenuate expression of
      palladin in Rcho-1 cells and fibroblasts, and disruption of the cytoskeleton was
      observed in both cell types. At longer times after antisense treatment,
      fibroblasts became fully rounded. These results suggest that palladin is required
      for the normal organization of the actin cytoskeleton and focal adhesions.

PMID- 10931876
TI  - New insights into the assembly of extracellular microfibrils from the analysis of
      the fibrillin 1 mutation in the tight skin mouse.
AB  - The Tight skin (Tsk) mutation is a duplication of the mouse fibrillin 1 (Fbn1)
      gene that results in a larger (418 kD) than normal (350 kD) protein; Tsk/+ mice
      display increased connective tissue, bone overgrowth, and lung emphysema. Lung
      emphysema, bone overgrowth, and vascular complications are the distinctive traits
      of mice with reduced Fbn1 gene expression and of Marfan syndrome (MFS) patients
      with heterozygous fibrillin 1 mutations. Although Tsk/+ mice produce equal
      amounts of the 418- and 350-kD proteins, they exhibit a relatively mild phenotype
      without the vascular complications that are associated with MFS patients and
      fibrillin 1-deficient mice. We have used genetic crosses, cell culture assays and
      Tsk-specific antibodies to reconcile this discrepancy and gain new insights into
      microfibril assembly. Mice compound heterozygous for the Tsk mutation and
      hypomorphic Fbn1 alleles displayed both Tsk and MFS traits. Analyses of
      immunoreactive fibrillin 1 microfibrils using Tsk- and species-specific
      antibodies revealed that the mutant cell cultures elaborate a less abundant and
      morphologically different meshwork than control cells. Cocultures of Tsk/Tsk
      fibroblasts and human WISH cells that do not assemble fibrillin 1 microfibrils,
      demonstrated that Tsk fibrillin 1 copolymerizes with wild-type fibrillin 1.
      Additionally, copolymerization of Tsk fibrillin 1 with wild-type fibrillin 1
      rescues the abnormal morphology of the Tsk/Tsk aggregates. Therefore, the studies
      suggest that bone and lung abnormalities of Tsk/+ mice are due to
      copolymerization of mutant and wild-type molecules into functionally deficient
      microfibrils. However, vascular complications are not present in these animals
      because the level of functional microfibrils does not drop below the critical
      threshold. Indirect in vitro evidence suggests that a potential mechanism for the
      dominant negative effects of incorporating Tsk fibrillin 1 into microfibrils is
      increased proteolytic susceptibility conferred by the duplicated Tsk region.

PMID- 10931875
TI  - An oligodendrocyte cell adhesion molecule at the site of assembly of the
      paranodal axo-glial junction.
AB  - Two major isoforms of the cell adhesion molecule neurofascin NF186 and NF155 are
      expressed in the central nervous system (CNS). We have investigated their roles
      in the assembly of the node of Ranvier and show that they are targeted to
      distinct domains at the node. At the onset of myelination, NF186 is restricted to
      neurons, whereas NF155 localizes to oligodendrocytes, the myelin-forming glia of
      the CNS. Coincident with axon ensheathment, NF155 clusters at the paranodal
      regions of the myelin sheath where it localizes in apposition to the axonal
      adhesion molecule paranodin/contactin-associated protein (Caspr1), which is a
      constituent of the septate junction-like axo-glial adhesion zone. Immunoelectron
      microscopy confirmed that neurofascin is a glial component of the paranodal axo
      glial junction. Concentration of NF155 with Caspr1 at the paranodal junctions of
      peripheral nerves is also a feature of Schwann cells. In Shiverer mutant mice,
      which assemble neither compact CNS myelin nor normal paranodes, NF155 (though
      largely retained at the cell body) is also distributed at ectopic sites along
      axons, where it colocalizes with Caspr1. Hence, NF155 is the first glial cell
      adhesion molecule to be identified in the paranodal axo-glial junction, where it
      likely interacts with axonal proteins in close association with Caspr1.

PMID- 10931877
TI  - The LIS1-related NUDF protein of Aspergillus nidulans interacts with the coiled
      coil domain of the NUDE/RO11 protein.
AB  - The nudF gene of the filamentous fungus Aspergillus nidulans acts in the
      cytoplasmic dynein/dynactin pathway and is required for distribution of nuclei.
      NUDF protein, the product of the nudF gene, displays 42% sequence identity with
      the human protein LIS1 required for neuronal migration. Haploinsufficiency of the
      LIS1 gene causes a malformation of the human brain known as lissencephaly. We
      screened for multicopy suppressors of a mutation in the nudF gene. The product of
      the nudE gene isolated in the screen, NUDE, is a homologue of the nuclear
      distribution protein RO11 of Neurospora crassa. The highly conserved NH(2)
      terminal coiled-coil domain of the NUDE protein suffices for protein function
      when overexpressed. A similar coiled-coil domain is present in several putative
      human proteins and in the mitotic phosphoprotein 43 (MP43) of X. laevis. NUDF
      protein interacts with the Aspergillus NUDE coiled-coil in a yeast two-hybrid
      system, while human LIS1 interacts with the human homologue of the NUDE/RO11
      coiled-coil and also the Xenopus MP43 coiled-coil. In addition, NUDF
      coprecipitates with an epitope-tagged NUDE. The fact that NUDF and LIS1 interact
      with the same protein domain strengthens the notion that these two proteins are
      functionally related.

PMID- 10931878
TI  - Dissecting the translocase and integrase functions of the Escherichia coli SecYEG
      translocon.
AB  - Recent evidence suggests that in Escherichia coli, SecA/SecB and signal
      recognition particle (SRP) are constituents of two different pathways targeting
      secretory and inner membrane proteins to the SecYEG translocon of the plasma
      membrane. We now show that a secY mutation, which compromises a functional SecY
      SecA interaction, does not impair the SRP-mediated integration of polytopic inner
      membrane proteins. Furthermore, under conditions in which the translocation of
      secretory proteins is strictly dependent on SecG for assisting SecA, the absence
      of SecG still allows polytopic membrane proteins to integrate at the wild-type
      level. These results indicate that SRP-dependent integration and SecA/SecB
      mediated translocation do not only represent two independent protein delivery
      systems, but also remain mechanistically distinct processes even at the level of
      the membrane where they engage different domains of SecY and different components
      of the translocon. In addition, the experimental setup used here enabled us to
      demonstrate that SRP-dependent integration of a multispanning protein into
      membrane vesicles leads to a biologically active enzyme.

PMID- 10931879
TI  - Axo-glial septate junctions. The maestro of nodal formation and myelination?

PMID- 10931880
TI  - Intermediate filaments on the move.

PMID- 10931881
TI  - Killed cultures of Escherichia coli can protect living organisms from acid
      stress.

PMID- 10931882
TI  - On the zymogenic character of chitin synthase 3.

PMID- 10931883
TI  - Authors' reply to cabib

PMID- 10931884
TI  - Transcription factors in Candida albicans - environmental control of
      morphogenesis.

PMID- 10931885
TI  - Families of transmembrane transporters selective for amino acids and their
      derivatives.

PMID- 10931886
TI  - The amino acid/polyamine/organocation (APC) superfamily of transporters specific
      for amino acids, polyamines and organocations.
AB  - In this paper an analysis of 175 currently sequenced transport proteins that
      comprise the amino acid/polyamine/organocation (APC) superfamily is reported.
      Members of this superfamily fall into 10 well-defined families that are either
      prokaryote specific, eukaryote specific or ubiquitous. Most of these proteins
      exhibit 12 probable transmembrane spanners (TMSs), but members of two of these
      families deviate from this pattern, exhibiting 10 and 14 TMSs. All members of
      these families are tabulated, their functional properties are reviewed and
      phylogenetic/sequence analyses define the evolutionary relationships of the
      proteins to each other. Evidence is presented that the APC superfamily may
      include two other currently recognized families that exhibit greater degrees of
      sequence divergence from APC superfamily members than do the proteins of the 10
      established families from each other. At least some of the protein members of
      these two distantly related families exhibit 11 established TMSs. Altogether, the
      APC superfamily probably includes 12 currently recognized families with members
      that exhibit exclusive specificity for amino acids and their derivatives but
      which can possess 10, 11, 12 or 14 TMSs per polypeptide chain.

PMID- 10931887
TI  - Phylogeny of related functions: the case of polyamine biosynthetic enzymes.
AB  - Genome annotation requires explicit identification of gene function. This task
      frequently uses protein sequence alignments with examples having a known
      function. Genetic drift, co-evolution of subunits in protein complexes and a
      variety of other constraints interfere with the relevance of alignments. Using a
      specific class of proteins, it is shown that a simple data analysis approach can
      help solve some of the problems posed. The origin of ureohydrolases has been
      explored by comparing sequence similarity trees, maximizing amino acid alignment
      conservation. The trees separate agmatinases from arginases but suggest the
      presence of unknown biases responsible for unexpected positions of some enzymes.
      Using factorial correspondence analysis, a distance tree between sequences was
      established, comparing regions with gaps in the alignments. The gap tree gives a
      consistent picture of functional kinship, perhaps reflecting some aspects of
      phylogeny, with a clear domain of enzymes encoding two types of ureohydrolases
      (agmatinases and arginases) and activities related to, but different from
      ureohydrolases. Several annotated genes appeared to correspond to a wrong
      assignment if the trees were significant. They were cloned and their products
      expressed and identified biochemically. This substantiated the validity of the
      gap tree. Its organization suggests a very ancient origin of ureohydrolases. Some
      enzymes of eukaryotic origin are spread throughout the arginase part of the
      trees: they might have been derived from the genes found in the early symbiotic
      bacteria that became the organelles. They were transferred to the nucleus when
      symbiotic genes had to escape Muller's ratchet. This work also shows that
      arginases and agmatinases share the same two manganese-ion-binding sites and
      exhibit only subtle differences that can be accounted for knowing the three
      dimensional structure of arginases. In the absence of explicit biochemical data,
      extreme caution is needed when annotating genes having similarities to
      ureohydrolases.

PMID- 10931888
TI  - The cellulose-binding activity of the PsB multiprotein complex is required for
      proper assembly of the spore coat and spore viability in Dictyostelium
      discoideum.
AB  - The terminal event of spore differentiation in the cellular slime mould
      Dictyostelium discoideum is the assembly of the spore coat, which surrounds the
      dormant amoeba and allows the organism to survive during extended periods of
      environmental stress. The spore coat is a polarized extracellular matrix composed
      of glycoproteins and cellulose. The process of spore coat formation begins by the
      regulated secretion of spore coat proteins from the prespore vesicles (PSVs).
      Four of the major spore coat proteins (SP96, PsB/SP85, SP70 and SP60) exist as a
      preassembled multiprotein complex within the PSVs. This complete complex has an
      endogenous cellulose-binding activity. Mutant strains lacking either the SP96 or
      SP70 proteins produce partial complexes that do not have cellulose-binding
      activity, while mutants lacking SP60 produce a partial complex that retains this
      activity. Using a combination of immunofluorescence microscopy and biochemical
      methods we now show that the lack of cellulose-binding activity in the SP96 and
      SP70 mutants results in abnormally assembled spore coats and spores with greatly
      reduced viability. In contrast, the SP60 mutant, in which the PsB complex retains
      its cellulose-binding activity, produces spores with apparently unaltered
      structure and viability. Thus, it is the loss of the cellulose-binding activity
      of the PsB complex, rather than the mere loss of individual spore coat proteins,
      that results in compromised spore coat structure. These results support the idea
      that the cellulose-binding activity associated with the complete PsB complex
      plays an active role in the assembly of the spore coat.

PMID- 10931889
TI  - Fruiting body development in Coprinus cinereus: regulated expression of two
      galectins secreted by a non-classical pathway.
AB  - Fruiting body formation in the basidiomycete Coprinus cinereus is a developmental
      process that occurs as a response of the mycelium to external stimuli. First,
      localized, highly branched hyphal structures (knots) are formed as a reaction to
      nutritional depletion. Hyphal-knot formation is repressed by light; however,
      light signals are essential for the development of the hyphal knot into an
      embryonic fruiting body (primordium) as well as karyogamy, meiosis and fruiting
      body maturation. The role of the different environmental signals in the initial
      phases of fruiting body development was analysed. It was observed that two fungal
      galectins, Cgl1 and Cgl2, are differentially regulated during fruiting body
      formation. cgl2 expression initiated in early stages of fruiting body development
      (hyphal knot formation) and was maintained until maturation of the fruiting body,
      whereas cgl1 was specifically expressed in primordia and mature fruiting bodies.
      Immunofluorescence and immuno-electron microscopy studies detected galectins
      within specific fruiting body tissues. They localized in the extracellular matrix
      and the cell wall but also in membrane-bound bodies in the cytoplasm.
      Heterologous expression of Cgl2 in Saccharomyces cerevisiae indicated that
      secretion of this protein occurred independently of the classical secretory
      pathway.

PMID- 10931890
TI  - Enzymically mediated bioprecipitation of uranium by a Citrobacter sp. : a
      concerted role for exocellular lipopolysaccharide and associated phosphatase in
      biomineral formation.
AB  - A Citrobacter sp. accumulated uranyl ion (UO2(2+)) via precipitation with
      phosphate ligand liberated by phosphatase activity. The onset and rate of uranyl
      phosphate deposition were promoted by NH4(+), forming NH(4)UO(2)PO(4), which has
      a lower solubility product than NaUO(2)PO(4). This acceleration decoupled the
      rate-limiting chemical crystallization process from the biochemical phosphate
      ligand generation. This provided a novel approach to monitor the cell-surface
      associated changes using atomic-force microscopy in conjunction with transmission
      electron microscopy and electron-probe X-ray microanalysis, to visualize
      deposition of uranyl phosphate at the cell surface. Analysis of extracted surface
      materials by (31)P NMR spectroscopy showed phosphorus resonances at chemical
      shifts of 0.3 and 2.0 p.p.m., consistent with monophosphate groups of the lipid A
      backbone of the lipopolysaccharide (LPS). Addition of fUO2(2+) to the extract
      gave a yellow precipitate which contained uranyl phosphate, while addition of
      Cd(2+) gave a chemical shift of both resonances to a single new resonance at 3
      p.p.m. Acid-phosphatase-mediated crystal growth exocellularly was suggested by
      the presence of acid phosphatase, localized by immunogold labelling, on the outer
      membrane and on material exuded from the cells. Metal deposition is proposed to
      occur via an initial nucleation with phosphate groups localized within the LPS,
      shown by other workers to be produced exocellularly in association with
      phosphatase. The crystals are further consolidated with additional, enzymically
      generated phosphate in close juxtaposition, giving high loads of LPS-bound uranyl
      phosphate without loss of activity and distinguishing this from simple
      biosorption, or periplasmic or cellular metal accumulation mechanisms.
      Accumulation of 'tethered' metal phosphate within the LPS is suggested to prevent
      fouling of the cell surface by the accumulated precipitate and localization of
      phosphatase exocellularly is consistent with its possible functions in
      homeostatis and metal resistance.

PMID- 10931891
TI  - Heterogeneous distribution of lysine 6-aminotransferase during cephamycin C
      biosynthesis in Streptomyces clavuligerus demonstrated using green fluorescent
      protein as a reporter.
AB  - The cellular distribution of the cephamycin biosynthetic enzyme lysine 6
      aminotransferase (LAT) has been studied in Streptomyces clavuligerus hyphae by
      confocal microscopy using the S65T mutant of green fluorescent protein (GFP) as a
      reporter. LAT mediates the first committed step in the biosynthesis of the
      secondary metabolite cephamycin C by S. clavuligerus. The enzymic activity of LAT
      varies with time during the growth of S. clavuligerus in liquid medium. To
      investigate if this temporal variation occurs uniformly amongst all hyphae, S.
      clavuligerus was transformed with a plasmid containing the LAT-encoding gene
      translationally fused to the GFP-encoding gene. The LAT-GFP fusion product
      displayed fluorescence spectral characteristics of GFP, and showed similar
      temporal characteristics of LAT activity compared to the wild-type strain of S.
      clavuligerus. The transformed strain exhibited a heterogeneous distribution of
      fluorescence in mycelia grown in liquid cultures. This distribution varied
      significantly as the batch progressed: only a fraction of the mycelia fluoresced
      in the early growth phase, whereas nearly all hyphae fluoresced by the late
      growth phase. Thereafter, a non-uniform distribution of fluorescence was again
      observed in the declining growth phase. A large fraction of the non-fluorescent
      cells in the declining growth phase were found to be non-viable. Observations of
      S. clavuligerus colonies grown on solid agar also showed variation of LAT-GFP
      expression at different stages of growth. These observations in the solid phase
      can be explained in terms of nutrient deprivation and signalling molecules. The
      results suggest that physiological differentiation of S. clavuligerus mycelia
      leading to cephamycin C biosynthesis is both temporally and spatially
      distributed. The findings also revealed that the observed heterogeneity was
      independent of the position of individual cell compartments within the hypha. The
      potential of GFP as a reporter for the quantitative study of cephamycin
      biosynthesis at the cellular level has also been demonstrated.

PMID- 10931892
TI  - Survival in experimental Candida albicans infections depends on inoculum growth
      conditions as well as animal host.
AB  - Evidence is presented that the growth medium used to prepare a Candida albicans
      challenge inoculum is a significant factor determining the ability of a fungus
      strain to gain an initial invasive hold immediately after injection into an
      animal host, and thus determining gross strain lethality. Three C. albicans
      strains, one known to be attenuated in virulence, were grown in two broth media
      and injected intravenously at different doses into female NMRI mice and male
      albino guinea pigs. For each fungus strain and challenge dose, survival was
      longer from inocula grown in a diluted, buffered peptone-based broth than from
      inocula grown in Sabouraud glucose broth. When animals were challenged
      intravenously with yeast doses adjusted to give the same mean survival time
      regardless of strain or growth medium, the progression of fungus tissue burdens
      (c. f.u. g(-1)) in kidneys, lungs, liver, spleen and brain samples was broadly
      similar for all three C. albicans strains but differed between the two animal
      hosts. The morphological form of C. albicans recovered from infected tissues
      differed at the level of both the fungus strain and the host tissue. Use of
      survival-standardized inocula provides a means of distinguishing differences in
      progression of experimental disseminated Candida infections that are related to
      the infecting strain from those related to the animal host.

PMID- 10931893
TI  - Pseudomonas aeruginosa cystic fibrosis clinical isolates produce exotoxin A with
      altered ADP-ribosyltransferase activity and cytotoxicity.
AB  - The role of Pseudomonas aeruginosa exotoxin A (ETA) as a virulence factor in the
      lung infections of cystic fibrosis (CF) patients is not well understood.
      Transcript-accumulation studies of bacterial populations in sputum reveal high
      levels of transcription of toxA, which encodes ETA, in some patients with CF.
      However, in general, tissue damage in the lungs of patients with CF does not seem
      to be consistent with a high level of expression of active ETA. To address this
      discrepancy the authors analysed the production and activity of ETA produced by a
      number of P. aeruginosa CF isolates. One CF isolate, strain 4384, transcribed
      toxA at levels similar to the hypertoxigenic strain PA103 but produced an ETA
      with reduced ADP-ribosyltransferase (ADPRT) activity. Complementation in trans of
      strain 4384 with the wild-type toxA and a mixed toxin experiment suggested the
      absence of inhibitory accessory factors within this strain. The toxA gene from
      strain 4384 was cloned and sequenced, revealing only three mutations in the gene,
      all within the enzymic domain. The first mutation changed Ser-410 to Asn. The
      second mutation was located within an alpha-helix, altering Ala-476 to Glu. The
      third mutation, Ser-515 to Gly, was found at the protein surface. To date, Ser
      410, Ala-476 and Ser-515 have not been reported to play a role in the ADPRT
      activity of ETA. However, it may be the combination of these mutations that
      reduces the enzymic activity of ETA produced by strain 4384. Expression of 4384
      toxA and wild-type toxA in an isogenic strain revealed that 4384 ETA had 10-fold
      less ADPRT activity than wild-type ETA. ETA purified from strain 4384 also
      demonstrated 10-fold less ADPRT activity as compared to wild-type ETA.
      Cytotoxicity assays of purified ETA from strain 4384 indicated that the
      cytotoxicity of 4384 ETA is not reduced; it may be slightly more toxic than wild
      type ETA. Analysis of five other CF isolates revealed a similar reduction in
      ADPRT activity to that seen in strain 4384. Sequence analysis of the enzymic
      domain of toxA from the five CF strains identified a number of mutations that
      could account for the reduction in ADPRT activity. These results suggest that
      some CF isolates produce an ETA with reduced enzymic activity and this may
      partially explain the pathogenesis of chronic lung infections of CF due to P.
      aeruginosa.

PMID- 10931894
TI  - The membrane phospholipids of Neisseria meningitidis and Neisseria gonorrhoeae as
      characterized by fast atom bombardment mass spectrometry.
AB  - The phospholipids of Neisseria meningitidis and Neisseria gonorrhoeae were
      characterized by fast atom bombardment (FAB)-MS and GLC-MS. The major
      phospholipids were phosphatidylethanolamine (PE), followed by
      phosphatidylglycerol (PG), with minor amounts of phosphatidic acid (PA) and trace
      levels of cardiolipin (DPG). All of the phospholipid preparations were variable
      in their fatty acyl substituents, which included C16:1, C16:0, C18:1, C14:0,
      C14:1 and C12:0. By MS/MS analysis, all pathogenic Neisseria spp. phospholipids
      contained a saturated fatty acyl substituent and either a saturated or
      unsaturated fatty acyl substituent in the sn-1 and sn-2 positions, respectively.
      Compared with enteric bacterial species, the phospholipids of N. meningitidis and
      N. gonorrhoeae have increased levels of phospholipids with short-chain fatty acyl
      residues (i.e. increases in C12:0, C14:1 and C14:0) and variable amounts of
      C18:1. The percentage of total PE and PG molecules with the shorter-chain fatty
      acids ranges from 35 to 47% and 42 to 66%, respectively, for N. meningitidis
      while these respective values are <10% and <5% for Escherichia coli. The
      variability and variety of meningococcal and gonococcal phospholipids suggest
      novel genetic mechanisms of neisserial phospholipid assembly and regulation,
      which may be important for the biology and pathogenesis of N. meningitidis and N.
      gonorrhoeae.

PMID- 10931895
TI  - Interactions between Streptococcus suis serotype 2 and different epithelial cell
      lines.
AB  - Streptococcus suis is an important swine pathogen responsible for cases of sudden
      death, septicaemia, meningitis, endocarditis and pneumonia. It is also recognized
      as a zoonotic agent in people occupationally exposed to pigs or pig products.
      Knowledge on virulence factors of S. suis serotype 2 is limited and the
      pathogenesis of the infection is poorly understood. It has been suggested that
      the disease due to S. suis serotype 2 begins with colonization of the
      nasopharyngeal epithelium, followed by either spread within the respiratory tract
      or invasion of the bloodstream. The mechanisms involved in the access of bacteria
      from the bloodstream to the central nervous system are unknown. It is possible
      that epithelial cells of the choroid plexus also play an important role in the
      pathogenesis of the meningitis. Different interactions (adhesion, invasion and
      toxic effects) of S. suis serotype 2 with epithelial cell lines [LLC-PK1, PK(15),
      A549, HeLa and MDCK] were studied and compared to those of a human pathogen which
      also causes meningitis, group B Streptococcus (GBS). The results showed that S.
      suis serotype 2, in contrast to GBS, is able to adhere to but not to invade
      epithelial cells. The adhesin(s) involved seem(s) to be partially masked by the
      capsule and are a part of the cell wall. The haemolysin produced by S. suis
      serotype 2 is responsible for a toxic effect observed on epithelial cells. The
      results described give additional evidence that pathogenesis of the infection
      differs between S. suis and GBS. In particular, it is possible that suilysin
      positive S. suis strains use adherence and cell injury, as opposed to direct
      cellular invasion, as part of a complicated multistep process which leads to
      bacteraemia and meningitis in pigs.

PMID- 10931896
TI  - Environmental regulation of glycosidase and peptidase production by Streptococcus
      gordonii FSS2.
AB  - The synthesis of cell-associated and secreted proteins by Streptococcus gordonii
      FSS2, an infective endocarditis (IE) isolate, was influenced by both
      environmental pH and carbon source. Controlling the pH at 7.5 in stirred batch
      cultures showed that cell-associated and secreted protein concentrations were
      increased during late exponential and stationary phase by 68% and 125%,
      respectively, compared with similar cultures without pH control. The expression
      of five glycosidase and eight peptidase activities were examined using fluorogen
      labelled synthetic substrates. Enzyme activities were significantly down
      regulated during exponential growth, increasing during stationary phase (P<0.01)
      whether the culture pH was controlled at pH 7.5 or allowed to fall naturally to
      pH 4.4. Culture-supernatant activities were significantly increased (P<0.05) when
      the pH was maintained at 6.0 or 7.5, indicating modulation of enzyme activity by
      pH. Growth under nitrogen-limitation/glucose-excess conditions resulted in a
      significant repression of cell-associated glycosidase activities (P<0.01), whilst
      in the supernatant, activities were generally reduced. The expression of
      peptidase activities in the culture supernatant did not significantly change. The
      results suggest a possible role for catabolite repression by glucose in
      regulating enzyme expression. When S. gordonii FSS2 was cultured with 50% (v/v)
      added heat-inactivated foetal bovine serum, several cell-associated enzyme
      activities increased initially but were then reduced as the culture time was
      extended to 116 h. Culture-supernatant enzyme activities (N-acetyl-beta-D
      glucosaminidase, N-acetyl-beta-D-galactosaminidase, thrombin, Hageman factor,
      collagenase and chymotrypsin), however, were significantly increased (P<0.01)
      over the same time period. The findings indicated that most of the important
      glycosidases synthesized by S. gordonii FSS2 were down-regulated by acid growth
      conditions and may also be subject to catabolite repression by glucose but
      conversely may be up-regulated by growth in serum. These results may have
      implications for streptococcal growth in an IE vegetation and in the mouth
      between meals or during sleep.

PMID- 10931897
TI  - Generation of lys-gingipain protease activity in Porphyromonas gingivalis W50 is
      independent of Arg-gingipain protease activities.
AB  - Porphyromonas gingivalis, a black-pigmenting anaerobe implicated in the aetiology
      of periodontal disease, contains two loci, rgpA and rgpB, encoding the
      extracellular Arg-X specific proteases (RGPs, Arg-gingipains), and kgp, which
      encodes a Lys-X specific protease (KGP, Lys-gingipain). The rgpA and kgp genes
      encode polyproteins comprising pro-peptide and catalytic domain with large N- and
      C-terminal extensions which require proteolytic processing at several Arg and Lys
      residues to generate mature enzymes. The product of rgpB contains only a pro
      peptide and the catalytic domain which requires processing at an Arg residue to
      generate active enzyme. An rgpA rgpB double mutant (E8) of P. gingivalis was
      constructed to study the role of RGPs in the processing of KGP. A kgp mutant
      (K1A) was also studied to investigate the role of KGP in the generation of RGPs.
      E8 was stable in the absence of the antibiotics tetracycline and clindamycin
      (selection markers for rgpA and rgpB, respectively) and exhibited the same
      pigmentation, colony morphology and identical growth rates to the parent W50
      strain in the absence of antibiotics, in both complex and chemically defined
      media. The KGP activity of E8, grown in the absence of tetracycline, in whole
      cultures and in culture supernatants (up to 6 d) was identical to levels in W50.
      However, in the presence of tetracycline in the growth medium, the level of KGP
      was reduced to 50% of levels present in whole cultures of W50. Since tetracycline
      had no effect on RGP or KGP activity when incorporated into assay buffer, this
      effect is most likely to be on the synthesis of Kgp polypeptide. K1A was also
      stable in the absence of antibiotics but was unable to pigment, and remained
      straw-coloured throughout growth. RGP activity in whole cultures of K1A was
      identical to levels in W50, but RGP activity in 6 d culture supernatants was
      reduced to 50% of levels present in W50. Thus, although KGP is not required for
      generation of RGP activity from RgpA and RgpB polypeptides, its absence affects
      the release/transport of RGP into culture supernatant.

PMID- 10931898
TI  - Expression of the phospho-beta-glycosidase ArbZ from Lactobacillus delbrueckii
      subsp. lactis in Lactobacillus helveticus: substrate induction and catabolite
      repression.
AB  - ArbZ from Lactobacillus delbrueckii subsp. lactis was previously shown to enable
      utilization of the beta-glucoside arbutin by Escherichia coli. The arbZ gene was
      cloned and expressed in the industrially used beta-glucoside-negative strain
      Lactobacillus helveticus 3036(62). The transformants were able to ferment not
      only arbutin, but also cellobiose, salicin and methyl-beta-glucoside (MbetaGlc).
      Cleavage of beta-glucosides by the transformants depended on the integrity of the
      cytoplasmic membrane, whereas in cell-free extracts only C(6)-phosphorylated
      substrates were hydrolysed. This suggested that ArbZ is a phospho-beta
      glycosidase. ArbZ activity in transformants of Lb. helveticus was subject to
      substrate induction mediated by the beta-glucosides arbutin, salicin and
      MbetaGlc, whereas cellobiose or the beta-galactoside lactose had no inducing
      effect. Northern blot analysis proved that induction by MbetaGlc was due to
      enhanced transcription of arbZ. Catabolite repression of arbZ induction was
      observed with glucose, mannose, fructose and galactose. The induction kinetics
      observed in the presence of these sugars indicated that at least two different
      mechanisms are operative in catabolite repression of arbZ in Lb. helveticus.

PMID- 10931899
TI  - Threshold level of protein kinase A activity and polarized growth in Mucor
      rouxii.
AB  - A model system to study the involvement of cAMP-mediated regulation of a cellular
      process such as hyphal morphogenesis was investigated. Impairment of polarized
      growth was observed when Mucor rouxii sporangiospores were grown in the presence
      of N(6)-cAMP analogues and of SQ 65,442, a cAMP phosphodiesterase inhibitor.
      Together with an effect on isodiametric growth, there was increased pigmentation,
      increased cell fragility and loss of cell adhesiveness. The total effect on
      morphology was attained even after adding the compounds shortly before germ-tube
      emergence; when added after this time growth continued in a non-polarized form
      and rounding of the germ tip was observed. The morphological effect was observed
      under all the nutritional and environmental conditions studied (aerobic
      conditions and defined medium with maltose or glucose, Casamino acids medium with
      glucose, or rich medium; anaerobic conditions with rich medium; and following a
      shift from anaerobiosis to aerobiosis). The time of germ-tube emergence, and the
      size of the cell at this time, was dependent on the growth medium. Protein kinase
      A (PKA) specific activity was followed during the germination process under three
      growth conditions. It was found that the total activity of PKA correlated with
      differentiation and not with growth, and that the total specific activity at the
      time of germination was the same, independent of the culture medium. The time of
      germ-tube emergence correlated with the time of attainment of a threshold level
      of PKA total specific activity. The concentration of dibutyryl-cAMP needed to
      promote isodiametric growth correlated with the total units of activity of PKA to
      be activated per cell. It was concluded that PKA is involved in the morphogenetic
      process of the fungus grown under all the nutritional and ambient conditions
      tested.

PMID- 10931900
TI  - A novel Cellvibrio mixtus family 10 xylanase that is both intracellular and
      expressed under non-inducing conditions.
AB  - Hydrolysis of the plant cell wall polysaccharides cellulose and xylan requires
      the synergistic interaction of a repertoire of extracellular enzymes. Recently,
      evidence has emerged that anaerobic bacteria can synthesize high levels of
      periplasmic xylanases which may be involved in the hydrolysis of small xylo
      oligosaccharides absorbed by the micro-organism. Cellvibrio mixtus, a saprophytic
      aerobic soil bacterium that is highly active against plant cell wall
      polysaccharides, was shown to express internal xylanase activity when cultured on
      media containing xylan or glucose as sole carbon source. A genomic library of C.
      mixtus DNA, constructed in lambdaZAPII, was screened for xylanase activity. The
      nucleotide sequence of the genomic insert from a xylanase-positive clone that
      expressed intracellular xylanase activity in Escherichia coli revealed an ORF of
      1137 bp (xynC), encoding a polypeptide with a deduced M(r) of 43413, defined as
      xylanase C (XylC). Probing a gene library of Pseudomonas fluorescens subsp.
      cellulosa with C. mixtus xynC identified a xynC homologue (designated xynG)
      encoding XylG; XylG and xynG were 67% and 63% identical to the corresponding C.
      mixtus sequences, respectively. Both XylC and XylG exhibit extensive sequence
      identity with family 10 xylanases, particularly with non-modular enzymes, and
      gene deletion studies on xynC supported the suggestion that they are single
      domain xylanases. Purified recombinant XylC had an M(r) of 41000, and displayed
      biochemical properties typical of family 10 polysaccharidases. However, unlike
      previously characterized xylanases, XylC was particularly sensitive to
      proteolytic inactivation by pancreatic proteinases and was thermolabile. C.
      mixtus was grown to late-exponential phase in the presence of glucose or xylan
      and the cytoplasmic, periplasmic and cell envelope fractions were probed with
      anti-XylC antibodies. The results showed that XylC was absent from the culture
      media but was predominantly present in the periplasm of C. mixtus cells grown on
      glucose, xylan, CM-cellulose or Avicel. These data suggest that C. mixtus can
      express non-modular internal xylanases whose potential roles in the hydrolysis of
      plant cell wall components are discussed.

PMID- 10931901
TI  - Use of a flexible cassette method to generate a double unmarked Mycobacterium
      tuberculosis tlyA plcABC mutant by gene replacement.
AB  - Progress in the field of mycobacterial research has been hindered by the
      inability to readily generate defined mutant strains of the slow-growing
      mycobacteria to investigate the function of specific genes. An efficient method
      is described that has been used to generate several mutants, including the first
      double unmarked deletion strain of Mycobacterium tuberculosis. Four mutants were
      constructed: a marked deletion of the plcABC cluster, which encodes three
      phospholipases C; separate unmarked deletions in plcABC and tlyA (encoding a
      haemolysin); and a double unmarked mutant tlyADelta plcABCDelta. To accomplish
      this, two series of vectors were designed, the first of which, named pNIL, allows
      manipulation of the target gene sequence at a variety of convenient restriction
      sites. The second series, named pGOAL, contains marker cassettes flanked by PAC:I
      restriction enzyme sites. The final suicide plasmid vectors were then obtained by
      cloning a marker cassette from a pGOAL vector into the single PAC:I site of the
      pNIL vector with the modified gene of interest. Finally, a two-step strategy was
      employed whereby single cross-over events were first selected, then screening for
      the second cross-over was carried out to yield the mutant strains. This technique
      will now allow the construction of potential vaccine strains without the
      inclusion of antibiotic resistance markers, the ability to make multiple defined
      mutations and the possibility of making more subtle defined mutations, such as
      point mutations.

PMID- 10931902
TI  - Phylogenetic associations of ISAa1 and IS150-like insertion sequences in
      Actinobacillus actinomycetemcomitans.
AB  - The distribution and number of two insertion sequences (ISs), ISAa1 and an IS150
      like element, in the genomes of a collection of Actinobacillus
      actinomycetemcomitans strains previously subjected to population genetic analysis
      were determined to obtain information about their stability and biological
      significance. The hybridization patterns revealed that these IS elements are
      widespread in the genome of A. actinomycetemcomitans strains and that their
      occurrence agrees with the overall population structure of the species. While the
      patterns of ISAa1 showed significant evolutionary stability, the IS150-like
      element showed evidence of intra-genomic variability even within members of the
      previously identified high-toxicity JP2 clone. Searching of the available genome
      sequence of strain HK1651 of the JP2 clone (www.genome.ou.edu/act.html) revealed
      close proximity of the IS elements to housekeeping genes, but no evidence of
      structural disruption of genes or integrations that may be presumed to influence
      pathogenic potential.

PMID- 10931903
TI  - The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all
      major classes of fungicides and some natural toxic compounds.
AB  - This paper reports the functional characterization of AtrBp, an ABC transporter
      from Aspergillus nidulans. AtrBp is a multidrug transporter and has affinity to
      substrates belonging to all major classes of agricultural fungicides and some
      natural toxic compounds. The substrate profile of AtrBp was determined by
      assessing the sensitivity of deletion and overexpression mutants of atrB to
      several toxicants. All mutants showed normal growth as compared to control
      isolates. DeltaatrB mutants displayed increased sensitivity to anilinopyrimidine,
      benzimidazole, phenylpyrrole, phenylpyridylamine, strobirulin and some azole
      fungicides. Increased sensitivity to the natural toxic compounds camptothecin
      (alkaloid), the phytoalexin resveratrol (stilbene) and the mutagen 4
      nitroquinoline oxide was also found. Overexpression mutants were less sensitive
      to a wide range of chemicals. In addition to the compounds mentioned above,
      decreased sensitivity to a broader range of azoles, dicarboximides, quintozene,
      acriflavine and rhodamine 6G was observed. Decreased sensitivity in
      overexpression mutants negatively correlated with levels of atrB expression.
      Interestingly, the overexpression mutants displayed increased sensitivity to
      dithiocarbamate fungicides, chlorothalonil and the iron-activated antibiotic
      phleomycin. Accumulation of the azole fungicide [(14)C]fenarimol by the
      overexpression mutants was lower as compared to the parental isolate,
      demonstrating that AtrBp acts by preventing intracellular accumulation of the
      toxicant. Various metabolic inhibitors increased accumulation levels of
      [(14)C]fenarimol in the overexpression mutants to wild-type levels, indicating
      that reduced accumulation of the fungicide in these mutants is due to increased
      energy-dependent efflux as a result of higher pump capacity of AtrBp.

PMID- 10931904
TI  - Primary sequence and enzymic properties of two modular endoglucanases, Cel5A and
      Cel45A, from the anaerobic fungus Piromyces equi.
AB  - Two endoglucanase cDNAs, designated cel5A and cel45A, were isolated from a cDNA
      library of the anaerobic fungus Piromyces equi. Sequence analysis revealed that
      cel5A has an open reading frame of 5142 bp and encodes a 1714 amino acid modular
      enzyme, Cel5A, with a molecular mass of 194847 Da. Cel5A consists of four
      catalytic domains homologous to family-5 glycosyl hydrolases, two C-terminal
      dockerins and one N-terminal dockerin. This is the first report of a complete
      gene containing tandem repeats of family-5 catalytic domains. The cDNA cel45A has
      an open reading frame of 1233 bp and encodes a 410 amino acid modular enzyme,
      Cel45A, with a molecular mass of 44380 Da. The catalytic domain, located at the C
      terminus, is homologous to the family-45 glycosyl hydrolases. Cel45A is the first
      family-45 enzyme to be described in an anaerobe. The presence of dockerins at the
      N and C termini of Cel5A and at the N terminus of Cel45A implies that both
      enzymes are part of the high-molecular-mass cellulose-degrading complex produced
      by Piromyces equi. The catalytic domain nearest the C terminus of Cel5A and the
      catalytic domain of Cel45A were hyperexpressed as thioredoxin fusion proteins,
      Trx-Cel5A' and Trx-Cel45A', and subjected to biochemical analysis. Trx-Cel5A' has
      a broad substrate range, showing activity against carboxymethylcellulose, acid
      swollen cellulose, barley beta-glucan, lichenin, carob galactomannan, p
      nitrophenyl beta-D-cellobiopyranoside and xylan. Trx-Cel45A' is active against
      carboxymethylcellulose, acid-swollen cellulose and the mixed linkage glucans,
      barley beta-glucan and lichenin.

PMID- 10931905
TI  - Gas vesicle genes in Planktothrix spp. from Nordic lakes: strains with weak gas
      vesicles possess a longer variant of gvpC.
AB  - In cyanobacteria of the genus Planktothrix:, there are three length variants of
      gvpC, the gene that encodes the outer protein of the gas vesicle. Sequence
      analyses indicated that the three allelic variants of gvpC differ principally in
      the presence or absence of a 99 nt and a 213 nt section. Strains with the new
      variant, gvpC(28), which encodes a 28 kDa form of GvpC, produce gas vesicles that
      collapse at the relatively low critical pressure (p(c)) of 0.61-0.75 MPa. The
      authors have identified 12 classes of gvp genotypes that differ in the number and
      arrangement of alternating gvpA-gvpC genes and in the presence of OmegaC, a
      fragment of gvpC. The gvpC(28) gene was found to be the most common variant of
      gvpC amongst 71 strains of Planktothrix: isolated from Nordic lakes: 34 strains
      contained only gvpC(28); 22 strains, which possessed only the shorter gvpC(20)
      gene, produced gas vesicles with a higher p(c) of 0.76-0.91 MPa; and 15 strains,
      which possessed both gvpC(20) and gvpC(28), also produced the stronger gas
      vesicles. Genotypes with only the gvpC(28) genes were more common amongst green
      Planktothrix: strains (33 out of 38) than red strains (one out of 33). It is
      suggested that there is competition between the strains producing the two types
      of gas vesicles, with the stronger forms favoured in lakes deeper than 60 m, in
      which the combination of cell turgor pressure and hydrostatic pressure can
      collapse the weaker gas vesicles. The fact that none of the Nordic lakes are
      deeper than 67 m would explain the absence of the gvpC(16)-containing strains
      that produce even narrower gas vesicles of p(c) 1.0-1.2 MPa, which are common in
      the much deeper Lake Zurich.

PMID- 10931906
TI  - Rapid detection of polyhydroxyalkanoate-accumulating bacteria isolated from the
      environment by colony PCR.
AB  - Colony PCR and semi-nested PCR techniques were employed for screening
      polyhydroxyalkanoate (PHA) producers isolated from the environment. Three
      degenerate primers were designed based on multiple sequence alignment results and
      were used as PCR primers to detect PHA synthase genes. Optimized colony PCR
      conditions were achieved by adding 3% DMSO combined with 1 M betaine to the
      reaction mixture. The sensitivity limit of the colony PCR was 1x 10(5) viable
      cells for Ralstonia eutropha. Nineteen PHA-positive bacteria were used to
      evaluate this PCR protocol; fifteen of the nineteen could be detected by colony
      PCR, and the other four could be detected by applying semi-nested PCR detection
      following colony PCR. In a preliminary screening project, 38 PHA-positive strains
      were isolated from environmental samples by applying the PCR protocol, and their
      phenotype was further confirmed by Nile blue A staining assay. By combining the
      colony PCR and semi-nested PCR techniques, a rapid, reliable and highly accurate
      detection method has been developed for detecting PHA producers. This protocol is
      suitable for screening large numbers of environmental isolates. The PHA
      accumulation ability of well-separated colonies isolated from environmental
      samples can be directly validated by PCR with no further culturing or chromosomal
      DNA extraction procedures. In addition to its application to the screening of
      wild-type isolates, the individual PCR-amplified product is also suitable as a
      specific probe for PHA operon cloning. The results suggest that the application
      of this PCR protocol for rapid detection of PHA producers from the environment is
      plausible.

PMID- 10931907
TI  - Genomic subpopulations within the species Pediococcus acidilactici detected by
      multilocus typing analysis: relationships between pediocin AcH/PA-1 producing and
      non-producing strains.
AB  - A high degree of genetic polymorphism among P. acidilactici strains was
      highlighted by a multilocus typing approach analysing several housekeeping genes
      and by sampling the whole genome using random amplified polymorphic DNA (RAPD)
      fingerprint analysis performed by using a single primer pedA gene targeted in low
      stringency amplification conditions. Restriction fragment length polymorphism of
      the rpoC, ldhD/L and mle genes, and a modified RAPD analysis, permitted the
      grouping of Pediococcus acidilactici strains in seven genotypes (I-VII).
      Genotypic results obtained by analysing housekeeping genes involved in the
      transcription/translation machinery and in primary metabolism were supported by
      phylogenetic analysis based on the partial 16S rDNA sequencing of a reference
      strain of each of the seven clusters obtained. Three of the seven genotypes
      detected showed relationships with pediocin AcH/PA-1 production and carbohydrate
      fermentation patterns: all pediocin-producing and sucrose-positive strains were
      grouped in genotype VII, melibiose-, sucrose- and raffinose-positive strains in
      genotype VI, and arabinose-positive strains in genotype V.

PMID- 10931908
TI  - Analysis of the beta-glucoside utilization (bgl) genes of Shigella sonnei:
      evolutionary implications for their maintenance in a cryptic state.
AB  - The pattern of expression of the genes involved in the utilization of aryl beta
      glucosides such as arbutin and salicin is different in the genus Shigella
      compared to Escherichia coli. The results presented here indicate that the
      homologue of the cryptic bgl operon of E. coli is conserved in Shigella sonnei
      and is the primary system involved in beta-glucoside utilization in the organism.
      The organization of the bgl genes in S. sonnei is similar to that of E. coli;
      however there are three major differences in terms of their pattern of
      expression. (i) The bglB gene, encoding phospho-beta-glucosidase B, is
      insertionally inactivated in S. sonnei. As a result, mutational activation of the
      silent bgl promoter confers an Arbutin-positive (Arb(+)) phenotype to the cells
      in a single step; however, acquiring a Salicin-positive (Sal(+)) phenotype
      requires the reversion or suppression of the bglB mutation in addition. (ii)
      Unlike in E. coli, a majority of the activating mutations (conferring the Arb(+)
      phenotype) map within the unlinked hns locus, whereas activation of the E. coli
      bgl operon under the same conditions is predominantly due to insertions within
      the bglR locus. (iii) Although the bgl promoter is silent in the wild-type strain
      of S. sonnei (as in the case of E. coli), transcriptional and functional analyses
      indicated a higher basal level of transcription of the downstream genes. This was
      correlated with a 1 bp deletion within the putative Rho-independent terminator
      present in the leader sequence preceding the homologue of the bglG gene. The
      possible evolutionary implications of these differences for the maintenance of
      the genes in the cryptic state are discussed.

PMID- 10931909
TI  - Characterization of a tonB mutation in Erwinia chrysanthemi 3937: TonB(Ech) is a
      member of the enterobacterial TonB family.
AB  - The pectinolytic enterobacterium Erwinia chrysanthemi 3937 causes a systemic
      disease in its natural host, the African violet (Saintpaulia: ionantha). It
      produces two structurally unrelated siderophores, chrysobactin and achromobactin.
      Chrysobactin makes a large contribution to invasive growth of the bacterium in
      its host. Insertion mutants of a chrysobactin-defective strain were constructed
      and screened on the universal CAS-agar medium used for siderophore detection. A
      set of mutants affected in the production of achromobactin were identified. This
      paper describes a mutant affected in the transport of all the ferrisiderophores
      used by the bacterium as iron sources. Molecular analysis revealed that the
      insertion mutation disrupts the tonB gene. The predicted Er. chrysanthemi TonB
      protein has a molecular mass of 27600 Da and shares 20-58% identity with the TonB
      proteins from 20 other bacterial species. The pathogenicity of the tonB mutant
      was assessed by inoculation of African violets. The impairment in the spread of
      symptoms was similar in the tonB mutant to that in chrysobactin-defective
      mutants. However, the pectinolytic activity, the major pathogenicity determinant
      in Er. chrysanthemi, appeared to be stimulated twofold in the tonB mutant.

PMID- 10931910
TI  - Analysis of aberrant virulence of Gibberella zeae following transformation
      mediated complementation of a trichothecene-deficient (Tri5) mutant.
AB  - Gibberella zeae causes wheat ear blight and produces trichothecene toxins in
      infected grain. In previous studies, trichothecene production in this fungus was
      disabled by specific disruption of the trichodiene synthase gene (Tri5) and was
      restored by two methods: gene reversion and transformation-mediated mutant
      complementation. In previous field tests of wheat ear blight, trichothecene
      nonproducing mutants were less virulent than the wild-type progenitor strain from
      which they were derived. Trichothecene-producing revertants also were restored to
      wild-type levels of virulence. In contrast, in the field test of wheat ear blight
      reported here, trichothecene-producing strains obtained by Tri5 mutant
      complementation were not restored to wild-type levels of virulence. The
      complemented mutants showed a slightly reduced radial growth compared to the wild
      type strain, but otherwise appeared normal in morphology, pigmentation and sexual
      fertility. Genetic analysis indicated that the aberrant virulence of a
      complemented mutant was likely due to non-target effects that occurred during the
      process of transforming the trichothecene-nonproducing mutant with Tri5. These
      results confirm previous findings that trichothecenes contribute to the virulence
      of G. zeae, but also demonstrate that manipulating this fungus in the laboratory
      may cause it to undergo subtle changes that reduce its virulence.

PMID- 10931911
TI  - Overproduction of an inducible extracellular serine protease improves biological
      control of Pythium ultimum by Stenotrophomonas maltophilia strain W81.
AB  - Stenotrophomonas maltophilia W81 can protect sugar beet against PYTHIUM:-mediated
      damping-off disease through the production of an extracellular protease. Here,
      the proteolytic enzyme of W81 was purified by anion-exchange chromatography and
      characterized as a serine protease. The purified enzyme was fungicidal against
      PYTHIUM: ultimum in vitro. Its synthesis was inducible by casein in W81, and
      mutagenesis of this strain using the luciferase (luxAB) reporter transposon Tn5
      764cd resulted in the isolation of two mutant derivatives (W81M3 and W81M4)
      capable of producing significantly increased levels of extracellular protease in
      the presence of casein. Strain W81M4 also exhibited increased chitinolytic
      activity. The luxAB fusions in strains W81M3 and W81M4 were highly expressed in
      the absence of casein but not in its presence, suggesting that the corresponding
      loci were involved in down-regulating extracellular protease production.
      Extracellular protease production in the W81 wild-type strain and protease
      overproduction in mutants W81M3 and W81M4 were also induced in the presence of
      the autoclaved fungal mycelium. In soil microcosms naturally infested by PYTHIUM:
      spp., inoculation of sugar beet seeds with W81M3 or W81M4 resulted in improved
      biocontrol of PYTHIUM:-mediated damping-off disease compared with W81, and the
      level of protection achieved was equivalent to that conferred by chemical
      fungicides. The wild-type W81 and its mutant derivatives did not differ in
      rhizosphere colonization. Therefore, the improved biocontrol ability of W81M3 and
      W81M4 resulted from their capacity to overproduce extracellular serine protease.

PMID- 10931912
TI  - Induction of the sexual stage of Pestalotiopsis microspora, a taxol-producing
      fungus.
AB  - Pestalotiopsis microspora, isolate NE-32, is an endophyte of the Himalayan yew
      (Taxus wallichiana) that produces taxol, an important chemotherapeutic drug used
      in the treatment of breast and ovarian cancers. Conditions were determined to
      induce the perfect stage (teleomorph) of this organism in the laboratory as a
      critical first step to study inheritance of taxol biosynthetic genes. The perfect
      stage of Pestalotiopsis microspora NE-32 forms in a period of 3-6 weeks on water
      agarose with dried yew needles at 16-20 degrees C with 12 h of light per day.
      Morphological analysis of the teleomorph and sequencing of the 18S rDNA indicates
      that Pestalosphaeria hansenii is the perfect stage of Pestalotiopsis microspora.
      Only certain plants (e.g. yews, some pines, pecan, oat and some barley cultivars)
      allow the production of perithecia. Exhaustive methylene chloride extraction of
      yew (Taxus cuspidata) needles removes their capacity to induce production of
      perithecia. The methylene chloride extract is able to induce formation of
      perithecia by strain NE-32 in a bioassay system utilizing the sterilized sheaths
      of the Cholla cactus (Opuntia bigelovii) spine, indicating that a chemical
      compound(s) in yew stimulates the formation of the perfect stage. This
      hydrophobic plant compound(s) has been designated the perithecial-stimulating
      factor (PSF). The data suggest that plant products may play a role in regulating
      the biology of endophytic microbes.

PMID- 10931913
TI  - Analysis of the splicing machinery in fission yeast: a comparison with budding
      yeast and mammals.
AB  - Based on genetic and bioinformatic analysis, 80 proteins from the newly sequenced
      Schizosaccharomyces pombe genome appear to be splicing factors. The fission yeast
      splicing factors were compared to those of Homo sapiens and Saccharomyces
      cerevisiae in order to determine the extent of conservation or divergence that
      has occurred over the billion years of evolution that separate these organisms.
      Our results indicate that many of the factors present in all three organisms have
      been well conserved throughout evolution. It is calculated that 38% of the
      fission yeast splicing factors are more similar to the human proteins than to the
      budding yeast proteins (>10% more similar or similar over a greater region). Many
      of the factors in this category are required for recognition of the 3' splice
      site. Ten fission yeast splicing factors, including putative regulatory factors,
      have human homologs, but no apparent budding yeast homologs based on sequence
      data alone. Many of the budding yeast factors that are absent in fission yeast
      are associated with the U1 and U4/U6.U5 snRNP. Collectively the data presented in
      this survey indicate that of the two yeasts, S.POMBE: contains a splicing
      machinery more closely reflecting the archetype of a spliceosome.

PMID- 10931914
TI  - From DNA biosensors to gene chips.
AB  - Wide-scale DNA testing requires the development of small, fast and easy-to-use
      devices. This article describes the preparation, operation and applications of
      biosensors and gene chips, which provide fast, sensitive and selective detection
      of DNA hybridization. Various new strategies for DNA biosensors and gene chips
      are examined, along with recent trends and future directions. The integration of
      hybridization detection schemes with the sample preparation process in a 'Lab-on
      a-Chip' format is also covered. While the use of DNA biosensors and gene chips is
      at an early stage, such devices are expected to have an enormous effect on future
      DNA diagnostics.

PMID- 10931915
TI  - Base J originally found in kinetoplastida is also a minor constituent of nuclear
      DNA of Euglena gracilis.
AB  - We have analyzed DNA of EUGLENA: gracilis for the presence of the unusual minor
      base beta-D-glucosyl-hydroxymethyluracil or J, thus far only found in
      kinetoplastid flagellates and in DIPLONEMA: Using antibodies specific for J and
      post-labeling of DNA digests followed by two-dimensional thin-layer
      chromatography of labeled nucleotides, we show that approximately 0.2 mole
      percent of EUGLENA: DNA consists of J, an amount similar to that found in DNA of
      Trypanosoma brucei. By staining permeabilized EUGLENA: cells with anti-J
      antibodies, we show that J is rather uniformly distributed in the EUGLENA:
      nucleus, and does not co-localize to a substantial extent with (GGGTTA)(n)
      repeats, the putative telomeric repeats of EUGLENA: Hence, most of J in EUGLENA:
      appears to be non-telomeric. Our results add to the existing evidence for a close
      phylogenetic relation between kinetoplastids and euglenids.

PMID- 10931916
TI  - Human 100-kDa homologous DNA-pairing protein is the splicing factor PSF and
      promotes DNA strand invasion.
AB  - Proteins promoting homologous pairing could be involved in various fundamental
      biological processes. Previously we detected two mammalian nuclear proteins of
      100 and 75 kDa able to promote homologous DNA pairing. Here we report isolation
      and characterisation of the human (h) 100-kDa DNA-pairing protein, hPOMp100, from
      HeLa nuclei. The peptide sequences of hPOMp100 revealed identity to the human
      splicing factor PSF and a DNA-binding subunit of p100/p52 heterodimer of unknown
      function. Bacterially expressed PSF promotes DNA pairing identical to that of
      hPOMp100. hPOMp100/PSF binds not only RNA but also both single-stranded (ss) and
      double-stranded (ds) DNA and facilitates the renaturation of complementary
      ssDNAs. More important, the protein promotes the incorporation of a ss
      oligonucleotide into a homologous superhelical dsDNA, D-loop formation. A D-loop
      is the first heteroduplex DNA intermediate generated between recombining DNA
      molecules. Moreover, this reaction could be implicated in re-establishing stalled
      replication forks. Consistent with this hypothesis, DNA-pairing activity of
      hPOMp100/PSF is associated with cellular proliferation. Significantly,
      phosphorylation of hPOMp100/PSF by protein kinase C inhibits its binding to RNA
      but stimulates its binding to DNA and D-loop formation and may represent a
      regulatory mechanism to direct this multifunctional protein to DNA metabolic
      pathways.

PMID- 10931917
TI  - K562 cells implicate increased chromatin accessibility in Alu transcriptional
      activation.
AB  - Alu repeats in K562 cells are unusually hypomethylated and far more actively
      transcribed than those in other human cell lines and somatic tissues. Also, the
      level of Alu RNA in K562 cells is relatively insensitive to cell stresses, namely
      heat shock, adenovirus infection and treatment with cycloheximide, which increase
      the abundance of Alu RNA in HeLa and 293 cells. Recent advances in understanding
      the interactions between DNA methylation, transcriptional activation and
      chromatin conformation reveal reasons for the constitutively high level of Alu
      expression in K562 cells. Methylation represses transcription of transiently
      transfected Alu templates in all cell lines tested but cell stresses do not
      relieve this repression suggesting that they activate Alu transcription through
      another pathway. A relatively large fraction of the Alus within K562 chromatin is
      accessible to restriction enzyme cleavage and cell stresses increase the
      chromatin accessibility of Alus in HeLa and 293 cells. Cell stress evidently
      activates Alu transcription by rapidly remodeling chromatin to recruit additional
      templates.

PMID- 10931918
TI  - DNA polymerase beta is required for efficient DNA strand break repair induced by
      methyl methanesulfonate but not by hydrogen peroxide.
AB  - The most frequent DNA lesions in mammalian genomes are removed by the base
      excision repair (BER) via multiple pathways that involve the replacement of one
      or more nucleotides at the lesion site. The biological consequences of a BER
      defect are at present largely unknown. We report here that mouse cells defective
      in the main BER DNA polymerase beta (Pol beta) display a decreased rate of DNA
      single-strand breaks (ssb) rejoining after methyl methanesulfonate damage when
      compared with wild-type cells. In contrast, Pol beta seems to be dispensable for
      hydrogen peroxide-induced DNA ssb repair, which is equally efficient in normal
      and defective cells. By using an in vitro repair assay on single abasic site
      containing circular duplex molecules, we show that the long-patch BER is the
      predominant repair route in Pol beta-null cell extract. Our results strongly
      suggest that the Pol beta-mediated single nucleotide BER is the favorite pathway
      for repair of N-methylpurines while oxidation-induced ssb, likely arising from
      oxidized abasic sites, are the substrate for long-patch BER.

PMID- 10931919
TI  - The glial transcription factor Sox10 binds to DNA both as monomer and dimer with
      different functional consequences.
AB  - Sox10 is an important transcriptional regulator in the neural crest and various
      neural-crest derived lineages, such as the Schwann cells of the peripheral
      nervous system. Recently, we identified the gene for myelin Protein zero (P(0))
      as a transcriptional target of Sox10 in Schwann cells, allowing for the first
      time a detailed analysis of Sox10 responsive elements and their functional
      interaction with Sox10. Here we show that Sox10 functions through two different
      types of DNA response elements, one that allows binding of monomers, and a second
      that favors cooperative binding of two molecules. This dimeric binding required
      the presence of two heptameric Sox binding sites in a specific orientation and
      spacing, and was mediated by an N-terminal region of Sox10 with high conservation
      in the related Sox9, which also exhibited dimeric binding. This argues that the
      conserved region has the capacity to function as a DNA-dependent dimerization
      domain. The interaction between Sox10 dimers and DNA differed dramatically from
      that of Sox10 monomers, as it drastically reduced the protein's off-rate and
      increased the protein-induced angle of DNA bending. These results indicate that
      functionally relevant interactions between Sox10 and DNA occur through completely
      different modes of binding.

PMID- 10931920
TI  - CHL1 is a nuclear protein with an essential ATP binding site that exhibits a size
      dependent effect on chromosome segregation.
AB  - Saccharomyces cerevisiae chl1 mutants have a significant increase in the rate of
      chromosome missegregation. CHL1 encodes a 99 kDa predicted protein with an ATP
      binding site consensus, a putative helix-turn-helix DNA binding motif, and
      homology to helicases. Using site-directed mutagenesis, I show that mutations
      that are predicted to abolish ATP binding in CHL1 inactivate its function in
      chromosome segregation. Furthermore, overexpression of these mutations interferes
      with chromosome transmission of a 125 kb chromosome fragment in a wild-type
      strain. Polyclonal antibodies against CHL1 show that CHL1 is predominantly in the
      nuclear fraction of S. CEREVISIAE: CHL1 function is more critical for the
      segregation of small chromosomes. In chl1Delta1/chl1Delta1 mutants, artificial
      circular or linear chromosomes <150 kb in size exhibit near random segregation
      (0.12 per cell division), whereas all chromosomes tested >225 kb were lost at
      rates (5 x 10(-)(3) per cell division) comparable to that observed for endogenous
      chromosome III. These results reveal an important role for ATPases/DNA helicases
      in chromosome segregation. Such enzymes may alter DNA topology to allow loading
      of proteins involved in maintaining sister chromatid cohesion.

PMID- 10931922
TI  - Proteomics of Mycoplasma genitalium: identification and characterization of
      unannotated and atypical proteins in a small model genome.
AB  - We present the results of a comprehensive analysis of the proteome of Mycoplasma
      genitalium (MG), the smallest autonomously replicating organism that has been
      completely sequenced. Our aim was to identify and characterize all soluble
      proteins in MG that are structurally and functionally uncharacterized. We were
      particularly interested in identifying proteins that differed significantly from
      typical globular proteins, for example, proteins which are unstructured in the
      absence of a 'partner' molecule or those that exhibit unusual thermodynamic
      properties. This work is complementary to other structural genomics projects
      whose primary aim is to determine the three-dimensional structures of proteins
      with unknown folds. We have identified all the full-length open reading frames
      (ORFs) in MG that have no homologs of known structure and are of unknown
      function. Twenty-five of the total 483 ORFs fall into this category and we have
      expressed, purified and characterized 11 of them. We have used circular dichroism
      (CD) to rapidly investigate their biophysical properties. Our studies reveal that
      these proteins have a wide range of structures varying from highly helical to
      partially structured to unfolded or random coil. They also display a variety of
      thermodynamic properties ranging from cooperative unfolding to no detectable
      unfolding upon thermal denaturation. Several of these proteins are highly
      conserved from mycoplasma to man. Further information about target selection and
      CD results is available at http://bioinfo.mbb.yale.edu/genome

PMID- 10931921
TI  - Human immunodeficiency virus type-1 reverse transcription can be inhibited in
      vitro by oligonucleotides that target both natural and synthetic tRNA primers.
AB  - Reverse transcription of human immunodeficiency virus type-1 is primed by
      cellular tRNA(Lys3), which is selectively packaged into viral particles where it
      is bound at its 3' terminus to a complementary sequence of viral RNA termed the
      primer binding site (PBS). Since cellular tRNA(Lys3) is highly conserved, it
      might conceivably serve as a good target for novel antagonists to block reverse
      transcriptase (RT) activity. In this study, we have examined a number of
      antisense oligodeoxyribonucleotides (ODNs) that are complementary to different
      parts of the tRNA primer and, therefore, may interfere with the initiation of RT
      mediated DNA synthesis. We found that the stability of complexes between
      synthetic tRNA(Lys3 )and ODNs was significantly increased when binding occurred
      via sequences involved in tertiary interactions of the tRNA. In particular, ODNs
      with complementarity to both the variable and TPsiC stem-loop of tRNA(Lys3 )bound
      with high affinity to both free tRNA(Lys3 )as well as to the binary
      tRNA(Lys3)/RNA complex. As a result, the initiation of DNA synthesis was severely
      compromised under these conditions. Moreover, RT-associated RNase H activity
      recognized the tRNA within this ternary tRNA(Lys3)/RNA/ODN complex as an RNA
      template and initiated its degradation. Both this RNase H degradation of
      tRNA(Lys3 )as well as the altered structure of the tRNA/RNA complex, due to the
      binding of the ODN, contributed to the inhibition of synthesis of viral DNA. The
      initiation of RT activity was almost completely blocked when using ODNs that
      interfered with intermolecular tRNA/RNA interactions that involved both the PBS
      and sequences outside the PBS. Similar findings were obtained with natural
      preparation of tRNA(Lys3).

PMID- 10931923
TI  - DNA bending induced by DNA (cytosine-5) methyltransferases.
AB  - DNA bending induced by six DNA (cytosine-5) methyltransferases was studied using
      circular permutation gel mobility shift assay. The following bend angles were
      obtained: M.BSP:RI (GG(m5)CC), 46-50 degrees; M.HAE:III (GG(m5)CC), 40-43
      degrees; M.SIN:I (GGW(m5)CC), 34-37 degrees; M.SAU:96I (GGN(m5)CC), 52-57
      degrees; M.HPA:II (C(m5)CGG), 30 degrees; and M.HHA:I (G(m5)CGC), 13 degrees. M.
      HAE:III was also tested with fragments carrying a methylated binding site, and it
      was found to induce a 32 degrees bend. A phase-sensitive gel mobility shift
      assay, using a set of DNA fragments with a sequence-directed bend and a single
      methyltransferase binding site, indicated that M.HAE:III and M. BSP:RI bend DNA
      toward the minor groove. The DNA curvature induced by M.HAE:III contrasts with
      the lack of DNA bend observed for a covalent M.HAE:III-DNA complex in an earlier
      X-ray study. Our results and data from other laboratories show a correlation
      between the bending properties and the recognition specificities of (cytosine-5)
      methyltransferases: enzymes recognizing a cytosine 3' to the target cytosine tend
      to induce greater bends than enzymes with guanine in this position. We suggest
      that the observed differences indicate different mechanisms employed by (cytosine
      5) methyltransferases to stabilize the helix after the target base has flipped
      out.

PMID- 10931924
TI  - DNase I digestion reveals alternating asymmetrical protection of the nucleosome
      by the higher order chromatin structure.
AB  - DNase I was used to probe the higher order chromatin structure in whole nuclei.
      The digestion profiles obtained were the result of single-stranded cuts and were
      independent of pH, type of divalent ion and chromatin repeat length. Furthermore,
      the protection from digestion of the DNA at the entry/exit points on the
      nucleosome was found to be caused not by the H1/H5 histone tails, but by the
      compact structure that these proteins support. In order to resolve symmetry
      ambiguities, DNase I digestion fragments over several nucleosome repeat lengths
      were analysed quantitatively and compared with computer simulations using
      combinations of the experimentally obtained rate constants (some of which were
      converted to 0 to simulate steric protection from DNase I digestion). A clear
      picture of precisely defined, alternating, asymmetrically protected nucleosomes
      emerged. The linker DNA is inside the fibre, while the nucleosomes are positioned
      above and below a helical path and/or with alternating orientation towards the
      dyad axis. The dinucleosomal modulation of the digestion patterns comes from
      alternate protection of cutting sites inside the nucleosome and not from
      alternating exposure to the enzyme of the linker DNA.

PMID- 10931925
TI  - Mapping analysis of the Xylella fastidiosa genome.
AB  - A cosmid library was made of the 2.7 Mb genome of the Gram-negative plant
      pathogenic bacterium Xylella fastidiosa and analysed by hybridisation mapping.
      Clones taken from the library as well as genomic restriction fragments of rarely
      cutting enzymes were used as probes. The latter served as a backbone for ordering
      the initial map contigs and thus facilitated gap closure. Also, the co-linearity
      of the cosmid map, and thus the eventual sequence, could be confirmed by this
      process. A subset of the eventual clone coverage was distributed to the Brazilian
      X.FASTIDIOSA: sequencing network. Data from this effort confirmed more
      quantitatively initial results from the hybridisation mapping that the redundancy
      of clone coverage ranged between 0 and 45-fold across the genome, while the
      average was 15-fold by experimental design. Reasons for this not unexpected
      fluctuation and the actual gaps are being discussed, as is the use of this effect
      for functional studies.

PMID- 10931927
TI  - In vitro expansion of mammalian telomere repeats by DNA polymerase alpha-primase.
AB  - Among the polymerases, DNA polymerase alpha-primase is involved in lagging strand
      DNA synthesis. A previous report indicated that DNA polymerase alpha-primase
      initiates primer RNA synthesis with purine bases on a single-stranded G-rich
      telomere repeat. In this study, we found that DNA polymerase alpha-primase
      precisely initiated with adenosine opposite the 3'-side thymidine in the G-rich
      telomere repeat 5'-(TTAGGG)(n)-3' under rATP-rich conditions. Then, DNA
      polymerase alpha-primase synthesized the nascent DNA fragments by extending the
      primer. It was remarkable that DNA polymerase alpha-primase further expanded the
      product DNA far beyond the length of the template DNA, as ladders of multiple
      hexanucleotides on polyacrylamide gel electrophoresis. Using an oligomer duplex
      5'-A(GGGTTA)(5)-3'/5'-(TAACCC)(5)T-3' as a template-primer, we show that both the
      Klenow fragment of Escherichia coli DNA polymerase I and HIV reverse
      transcriptase could expand telomere DNA sequences as well, giving products
      greater than the size of the template DNA. The maximum product lengths with these
      polymerases were approximately 40-90 nt longer than the template length. Our data
      imply that DNA polymerases have an intrinsic activity to expand the
      hexanucleotide repeats of the telomere sequence by a slippage mechanism and that
      DNA polymerase alpha uses both the repeat DNA primers and the de novo RNA primers
      for expansion. On the other hand, a plasmid harboring a eukaryotic telomere
      repeat showed remarkable genetic instability in E.coli. The telomere repeats
      exhibited either expansions or deletions by multiple hexanucleotide repeats
      during culture for a number of generations, suggesting involvement of the
      slippage mechanism in the instability of telomeric DNA in vivo.

PMID- 10931926
TI  - Differential effects of the protein cofactor on the interactions between an RNase
      P ribozyme and its target mRNA substrate.
AB  - RNase P from Escherichia coli is a tRNA-processing enzyme and consists of a
      catalytic RNA subunit (M1 RNA) and a protein component (C5 protein). M1GS, a gene
      targeting ribozyme derived from M1, can cleave a herpes simplex virus 1 mRNA
      efficiently in vitro and inhibit its expression effectively in viral-infected
      cells. In this study, the effects of C5 on the interactions between a M1GS
      ribozyme and a model mRNA substrate were investigated by site-specific UV
      crosslink mapping. In the presence of the protein cofactor, the ribozyme regions
      crosslinked to the substrate sequence 3' immediately to the cleavage site were
      similar to those found in the absence of C5. Meanwhile, some of the ribozyme
      regions (e.g. P12 and J11/12) that were crosslinked to the leader sequence 5'
      immediately to the cleavage site in the presence of C5 were different from those
      regions (e.g. P3 and P4) found in the absence of the protein cofactor and were
      not among those that are believed to interact with a tRNA. Understanding how C5
      affects the specific interactions between the ribozyme and its target mRNA may
      facilitate the development of gene-targeting ribozymes that function effectively
      in vivo, in the presence of cellular proteins.

PMID- 10931928
TI  - The precursor strategy: terminus methoxyoxalamido modifiers for single and
      multiple functionalization of oligodeoxyribonucleotides.
AB  - Synthesis of new terminus modifiers, bearing, along with a phosphoramidite
      moiety, one, two or four methoxyoxalamido (MOX) precursor groups, is described.
      These modifiers are introduced onto the 5'-end of a synthetic
      oligodeoxyribonucleotide as the last step of an automated synthesis to form the
      MOX precursor oligonucleotide. The MOX groups are then post-synthetically
      derivatized with an appropriate primary amine to construct a 5'-modified
      oligonucleotide. The efficiency and simplicity of the novel modifying strategy
      were demonstrated in the synthesis of a number of 5'-functionalized
      oligonucleotides.

PMID- 10931929
TI  - The spherulites(TM): a promising carrier for oligonucleotide delivery.
AB  - Concentric multilamellar microvesicles, named spherulites(TM), were evaluated as
      an oligonucleotide carrier. Up to 80% oligonucleotide was encapsulated in these
      vesicles. The study was carried out on two different spherulite(TM) formulations.
      The spherulite(TM) size and stability characteristics are presented. Delivery of
      encapsulated oligonucleotide was performed on a rat hepatocarcinoma and on a
      lymphoblastoid T cell line, both expressing the luciferase gene. We showed that
      spherulites(TM) were able to transfect both adherent and suspension cell lines
      and deliver the oligonucleotide to the nucleus. Moreover, 48-62% luciferase
      inhibition was obtained in the rat hepatocarcinoma cell line when the antisense
      oligonucleotide targeted to the luciferase coding region was encapsulated at 500
      nM concentration in spherulites(TM) of different compositions.

PMID- 10931930
TI  - Recognition of native DNA methylation by the PvuII restriction endonuclease.
AB  - Recognizing the methylation status of specific DNA sequences is central to the
      function of many systems in eukaryotes and prokaryotes. Restriction-modification
      systems have to distinguish between 'self' and 'non-self' DNA and depend on the
      inability of restriction endonucleases to cleave their DNA substrates when the
      DNA is appropriately methylated. These endonucleases thus provide a model system
      for studying the recognition of DNA methylation by proteins. We have
      characterized the interaction of R.PVU:II with DNA containing the physiologically
      relevant N4-methylcytosine modification. R.PVU:II binds (N4m)C-modified DNA and
      cleaves it very slowly. Methylated strands in hemimethylated duplexes were
      cleaved at a higher rate than in fully methylated duplexes, in parallel with a
      higher binding affinity for hemimethylated DNA. The co-crystal structures of
      R.PVU:II-DNA, together with a mutagenesis study, have implicated specific amino
      acids in recognition of the methylatable base; one of these is His84. We report
      that replacing His84 with Ala reduced the rate of cleavage of unmodified DNA but,
      in contrast, slightly increased the cleavage of (N4m)C-modified DNA.

PMID- 10931931
TI  - Molecular characterization of an acidic region deletion mutant of Cockayne
      syndrome group B protein.
AB  - Cockayne syndrome (CS) is a human genetic disorder characterized by post-natal
      growth failure, neurological abnormalities and premature aging. CS cells exhibit
      high sensitivity to UV light, delayed RNA synthesis recovery after UV irradiation
      and defective transcription-coupled repair (TCR). Two genetic complementation
      groups of CS have been identified, designated CS-A and CS-B. The CSB gene encodes
      a helicase domain and a highly acidic region N-terminal to the helicase domain.
      This study describes the genetic characterization of a CSB mutant allele encoding
      a full deletion of the acidic region. We have tested its ability to complement
      the sensitivity of UV61, the hamster homolog of human CS-B cells, to UV and the
      genotoxic agent N-acetoxy-2-acetylaminofluorene (NA-AAF). Deleting 39 consecutive
      amino acids, of which approximately 60% are negatively charged, did not impact on
      the ability of the protein to complement the sensitive phenotype of UV61 cells to
      either UV or NA-AAF. Our data indicate that the highly acidic region of CSB is
      not essential for the TCR and general genome repair pathways of UV- and NA-AAF
      induced DNA lesions.

PMID- 10931932
TI  - Combinatorial regulation of phospholipid biosynthetic gene expression by the
      UME6, SIN3 and RPD3 genes.
AB  - The Ume6p-Sin3p-Rpd3p complex negatively regulates expression of genes containing
      a Ume6p binding site. However, these regulatory proteins also function
      independently to regulate gene expression both negatively and positively. The
      model system for this combinatorial regulation is the yeast phospholipid
      biosynthetic pathway. Sin3p negatively regulates the INO1, CHO1, CHO2 and OPI3
      genes while Ume6p negatively regulates the INO1 gene and positively regulates the
      other genes. We have suggested that the positive regulation results from indirect
      effects on expression of the INO2 transcriptional activator gene. Here, we
      demonstrate that the effect of Ume6p on INO2 gene expression is also indirect. We
      also show that Rpd3p is a negative regulator of phospholipid biosynthetic gene
      expression. The ability of Ume6p, Sin3p and Rpd3p to differentially regulate
      expression of the phospholipid biosynthetic genes affects phospholipid
      composition. A sin3 mutant strain lacks detectable levels of
      phosphatidylethanolamine and elevated levels of phosphatidylcholine (PC) and a
      rpd3 mutant strain has reduced levels of PC. These alterations in membrane
      composition suggest that there may exist additional differences in regulation of
      phospholipid biosynthetic gene expression and that membrane compositions may be
      coordinated with other biological processes regulated by Ume6p, Sin3p and Rpd3p.

PMID- 10931934
TI  - The roles of mutS, sbcCD and recA in the propagation of TGG repeats in
      Escherichia coli.
AB  - A 24 triplet TGG.CCA repeat array shows length- and orientation-dependent
      propagation when present in the plasmid pUC18. When TGG(24) is present as
      template for leading-strand synthesis, plasmid recovery is normal in all strains
      tested. However, when it acts as template for lagging-strand synthesis, plasmid
      propagation is seriously compromised. Plasmids carrying deletions in the 5' side
      of this sequence can be isolated and products carrying 15 TGG triplets do not
      significantly interfere with plasmid propagation. Mutations in sbcCD, mutS and
      recA significantly improve the recovery of plasmids with TGG(24) on the lagging
      strand template. These findings suggest that TGG(24) can fold into a structure
      that can interfere with DNA replication in vivo but that TGG(15) cannot.
      Furthermore, since the presence of the MutS and SbcCD proteins are required for
      propagation interference, it is likely that stabilisation of mismatched base
      pairs and secondary structure cleavage are implicated. In contrast, there is no
      correlation of triplet repeat expansion and deletion instability with predicted
      DNA folding. These results argue for a dissociation of the factors affecting DNA
      fragility from those affecting trinucleotide repeat expansion-contraction
      instability.

PMID- 10931935
TI  - Efficient purification of DNA fragments using a protein binding membrane.
AB  - A novel and efficient method has been developed for isolation of correctly
      digested DNA fragments without the use of classic size-dependent electrophoretic
      separation methods. To achieve this, DNA fragments are end-labelled by haptens.
      After specific endonuclease digestion of the hapten-labelled DNA, the DNA is
      incubated with a protein that specifically binds to the hapten. The incubation
      mixture is then passed through a cartridge containing a protein-binding membrane
      that does not bind DNA. Undigested and partly digested DNA are retained on the
      membrane, while correctly digested DNA is selectively recovered for use in
      further downstream applications.

PMID- 10931933
TI  - Protein kinase-A dependent phosphorylation of transcription enhancer factor-1
      represses its DNA-binding activity but enhances its gene activation ability.
AB  - The cAMP-dependent signaling pathway has been implicated in cardiac cell
      growth/differentiation and muscle gene transcription. Previously, we have
      identified a cAMP-inducible E-box/M-CAT hybrid motif in the cardiac alpha-myosin
      heavy chain (alpha-MHC) gene promoter. The two factors, TEF-1 and Max, that bind
      to this motif are found to physically associate with each other and exert a
      positive cooperative effect for gene regulation. Here we show that TEF-1, but not
      Max, is a substrate for protein kinase-A (PK-A)-dependent phosphorylation. TEF-1
      is phosphorylated by PK-A at residue serine-102. This post-translational
      modification of TEF-1 repressed its DNA-binding activity, but not its ability to
      interact with the Max protein. Replacement of serine-102 in TEF-1 by a neutral or
      a charged amino acid did not abolish its DNA-binding ability, suggesting that
      changing a charge at the 102 amino-acid position of TEF-1 was not sufficient to
      inhibit its DNA-binding activity. We also show that PK-A response of the alpha
      MHC gene is stimulated by the presence of wild-type TEF-1 but not by mutant TEF-1
      having serine-102 replaced by alanine, suggesting that phosphorylation at this
      residue accounts for the cAMP/PK-A response of the gene. Thus, these data
      demonstrate that TEF-1 is a direct target of cAMP/PK-A signaling in cardiac
      myocytes.

PMID- 10931936
TI  - A novel method for constructing gene-targeting vectors.
AB  - We developed a simple and rapid method for constructing knockout vectors using
      inverse-PCR (IPCR). The method consists of three steps: (i) digestion of a target
      bacterial artificial chromosome with several restriction enzymes (six-base
      cutters) followed by self-ligation; (ii) IPCR using circular DNAs as templates
      and two primers which are oriented in opposite directions; and (iii) cloning into
      a vector containing a positive selection marker, which results in a typical
      replacement knockout vector. We successfully targeted three mouse genes including
      the HPRT gene using this method. Compared with the conventional method, this
      method requires much less time (no more than 3 weeks). Notably, this method
      requires only small amounts of sequence information (several hundred base pairs
      such as is available from expressed sequence tags) and can be extended to a
      systematic mass production of targeting vectors applicable to many organisms,
      including yeast.

PMID- 10931937
TI  - Directed evolution of green fluorescent protein by a new versatile PCR strategy
      for site-directed and semi-random mutagenesis.
AB  - To develop a simple, speedy, economical and widely applicable method for multiple
      site mutagenesis, we have substantially modified the Quik-Change Site-Directed
      Mutagenesis Kit protocol (Stratagene, La Jolla, CA). Our new protocol consists of
      (i) a PCR reaction using an in vitro technique, LDA (ligation-during
      amplification), (ii) a DPN:I treatment to digest parental DNA and to make
      megaprimers and (iii) a synthesis of double-stranded plasmid DNA for bacterial
      transformation. While the Quik Change Kit protocol introduces mutations at a
      single site, requiring two complementary mutagenic oligonucleotides, our new
      protocol requires only one mutagenic oligonucleotide for a mutation site, and can
      introduce mutations in a plasmid at multiple sites simultaneously. A targeting
      efficiency >70% was consistently achieved for multiple-site mutagenesis.
      Furthermore, the new protocol allows random mutagenesis with degenerative
      primers, because it does not use two complementary primers. Our mutagenesis
      strategy was successfully used to alter the fluorescence properties of green
      fluorescent protein (GFP), creating a new-color GFP mutant, cyan-green
      fluorescent protein (CGFP). An eminent feature of CGFP is its remarkable
      stability in a wide pH range (pH 4-12). The use of CGFP would allow us to monitor
      protein localization quantitatively in acidic organelles in secretory pathways.

PMID- 10931938
TI  - A gene encoding a sphingolipid biosynthesis enzyme determines the sensitivity of
      Saccharomyces cerevisiae to an antifungal plant defensin from dahlia (Dahlia
      merckii).
AB  - We have previously identified a Saccharomyces cerevisiae mutant that is markedly
      more resistant than wild-type to Dahlia merckii antimicrobial peptide 1 (DmAMP1),
      an antifungal plant defensin isolated from seeds of dahlia (Dahlia merckii). A
      complementation approach was followed that consisted of the introduction of a
      genomic library of DmAMP1-sensitive wild-type yeast into the DmAMP1-resistant
      yeast mutant and screening for restored sensitivity to DmAMP1. The gene
      determining sensitivity of S. cerevisiae to DmAMP1 was identified as IPT1, a gene
      encoding an enzyme involved in the last step of the synthesis of the sphingolipid
      mannose-(inositol-phosphate)(2)-ceramide. Strains with a nonfunctional IPT1
      allele lacked mannose-(inositol-phosphate)(2)-ceramide in their plasma membranes,
      bound significantly less DmAMP1 compared with wild-type strains, and were highly
      resistant to DmAMP1-mediated membrane permeabilization. All of these phenotypic
      deviations could be restored by reintroduction of a functional IPT1 gene. Our
      data support a model in which membrane patches containing sphingolipids act as
      binding sites for DmAMP1 or, alternatively, are required to anchor membrane or
      cell wall-associated proteins, which themselves interact with DmAMP1.

PMID- 10931940
TI  - BACE2, a beta -secretase homolog, cleaves at the beta site and within the amyloid
      beta region of the amyloid-beta precursor protein.
AB  - Production of amyloid-beta protein (Abeta) is initiated by a beta-secretase that
      cleaves the Abeta precursor protein (APP) at the N terminus of Abeta (the beta
      site). A recently identified aspartyl protease, BACE, cleaves the beta site and
      at residue 11 within the Abeta region of APP. Here we show that BACE2, a BACE
      homolog, cleaves at the beta site and more efficiently at a different site within
      Abeta. The Flemish missense mutation of APP, implicated in a form of familial
      Alzheimer's disease, is adjacent to this latter site and markedly increases Abeta
      production by BACE2 but not by BACE. BACE and BACE2 respond identically to
      conservative beta-site mutations, and alteration of a common active site Arg
      inhibits beta-site cleavage but not cleavage within Abeta by both enzymes. These
      data suggest that BACE2 contributes to Abeta production in individuals bearing
      the Flemish mutation, and that selective inhibition of these highly similar
      proteases may be feasible and therapeutically advantageous.

PMID- 10931939
TI  - Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons.
AB  - Neurotrophins influence the epigenetic shaping of the vertebrate nervous system
      by regulating neuronal numbers during development and synaptic plasticity. Here
      we attempt to determine whether these growth factors can also regulate
      neurotransmitter plasticity. As a model system we used the selection between
      noradrenergic and cholinergic neurotransmission by paravertebral sympathetic
      neurons. Developing sympathetic neurons express the neurotrophin receptors TrkA
      and TrkC, two highly related receptor tyrosine kinases. Whereas the TrkA ligand
      nerve growth factor (NGF) has long been known to regulate both the survival and
      the expression of noradrenergic traits in sympathetic neurons, the role of TrkC
      and of its ligand neurotrophin-3 (NT3) has remained unclear. We found that TrkC
      expression in the avian sympathetic chain overlaps substantially with that of
      choline acetyltransferase. In sympathetic chain explants, transcripts of the
      cholinergic marker genes choline acetyltransferase and vasoactive intestinal
      polypeptide were strongly enriched in the presence of NT3 compared with NGF,
      whereas the noradrenergic markers tyrosine hydroxylase and norepinephrine
      transporter were reduced. The transcription factor chicken achaete scute homolog
      1 was coexpressed with cholinergic markers. The effects of NT3 are reversed and
      antagonized by NGF. They are independent of neuronal survival and developmentally
      regulated. These results suggest a role for NT3 as a differentiation factor for
      cholinergic neurons and establish a link between neurotrophins and
      neurotransmitter plasticity.

PMID- 10931941
TI  - Interaction of pseudomonas aeruginosa with epithelial cells: identification of
      differentially regulated genes by expression microarray analysis of human cDNAs.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that plays a major role in
      lung function deterioration in cystic fibrosis patients. To identify critical
      host responses during infection, we have used high-density DNA microarrays,
      consisting of 1,506 human cDNA clones, to monitor gene expression in the A549
      lung pneumocyte cell line during exposure to P. aeruginosa. We have identified
      host genes that are differentially expressed upon infection, several of which
      require interaction with P. aeruginosa and the expression of the major subunit of
      type IV pili, PilA. Differential expression of genes involved in various cellular
      functions was identified, and we selected the gene encoding the transcription
      factor interferon regulatory factor 1 (IRF-1) for further analysis. The levels of
      the IRF-1 transcript increased 3- to 4-fold in A549 cells after adherence by P.
      aeruginosa. A similar increase of IRF-1 mRNA was observed in A549 cells exposed
      to wild-type P. aeruginosa when compared to an isogenic, nonpiliated strain.
      However, this difference was abolished when serum was present during the
      incubation of bacteria. Exposure of A549 cells to purified P. aeruginosa
      lipopolysaccharide did not result in a significant increase in IRF-1 mRNA.
      Although the P. aeruginosa-induced increased IRF-1 expression depends on the
      presence of bacterial adhesin, our findings do not preclude the possibility that
      other bacterial products are responsible for IRF-1 activation, which is enhanced
      by bacterial adherence to cells. These data show that microarray technology can
      be an important tool for studying the complex interplay between bacterial
      pathogens and host.

PMID- 10931942
TI  - Glutamate translocation of the neuronal glutamate transporter EAAC1 occurs within
      milliseconds.
AB  - The activity of glutamate transporters is essential for the temporal and spatial
      regulation of the neurotransmitter concentration in the synaptic cleft, and thus,
      is crucial for proper excitatory signaling. Initial steps in the process of
      glutamate transport take place within a time scale of microseconds to
      milliseconds. Here we compare the steady-state and pre-steady-state kinetics of
      the neuronal heterologously expressed glutamate transporter EAAC1, cloned from
      the mammalian retina. Rapid transporter dynamics, as measured by using whole-cell
      current recordings, were resolved by applying the laser-pulse photolysis
      technique of caged glutamate with a time resolution of 100 micros. EAAC1-mediated
      pre-steady-state currents are composed of two components: A transport current
      generated by substrate-coupled charge translocation across the membrane and an
      anion current that is not stoichiometrically coupled to glutamate transport. The
      two currents were temporally resolved and studied independently. Our results
      indicate a rapid glutamate-binding step occurring on a submillisecond time scale
      that precedes subsequent slower electrogenic glutamate translocation across the
      membrane within a few milliseconds. The voltage-dependent steady-state turnover
      time constant of the transporter is about 1/10 as fast, indicating that glutamate
      translocation is not rate limiting. A third process, the transition to an anion
      conducting state, is delayed with respect to the onset of glutamate transport.
      These rapid transporter reaction steps are summarized in a sequential shuttle
      model that quantitatively accounts for the results obtained here and are
      discussed regarding their functional importance for glutamatergic
      neurotransmission in the central nervous system.

PMID- 10931943
TI  - Htra2-beta 1 stimulates an exonic splicing enhancer and can restore full-length
      SMN expression to survival motor neuron 2 (SMN2).
AB  - Spinal muscular atrophy (SMA), a common motor neuron disease in humans, results
      from loss of functional survival motor neuron (SMN1) alleles. A nearly identical
      copy of the gene, SMN2, fails to provide protection from SMA because of a single
      translationally silent nucleotide difference in exon 7. This likely disrupts an
      exonic splicing enhancer and causes exon 7 skipping, leading to abundant
      production of a shorter isoform, SMN2Delta7. The truncated transcript encodes a
      less stable protein with reduced self-oligomerization activity that fails to
      compensate for the loss of SMN1. This report describes the identification of an
      in vivo regulator of SMN mRNA processing. Htra2-beta1, an SR-like splicing factor
      and ortholog of Drosophila melanogaster transformer-2, promoted the inclusion of
      SMN exon 7, which would stimulate full-length SMN2 expression. Htra2-beta1
      specifically functioned through and bound an AG-rich exonic splicing enhancer in
      SMN exon 7. This effect is not species-specific as expression of Htra2-beta1 in
      human or mouse cells carrying an SMN2 minigene dramatically increased production
      of full-length SMN2. This demonstrates that SMN2 mRNA processing can be modulated
      in vivo. Because all SMA patients retain at least one SMN2 copy, these results
      show that an in vivo modulation of SMN RNA processing could serve as a
      therapeutic strategy to prevent SMA.

PMID- 10931945
TI  - TARP: a nuclear protein expressed in prostate and breast cancer cells derived
      from an alternate reading frame of the T cell receptor gamma chain locus.
AB  - Previously, we identified the expression of a prostate-specific form of T cell
      receptor gamma chain (TCRgamma) mRNA in the human prostate and demonstrated that
      it originates from epithelial cells and not from infiltrating T lymphocytes.
      Here, we show that this prostate-specific transcript is also expressed in three
      breast cancer cell lines and breast cancer tissues. Analysis of the cDNA sequence
      predicts that this transcript can encode two protein products of 7 and 13 kDa,
      and in vitro translation experiments showed that both proteins were made. The
      longer ORF encodes a 13-kDa truncated version of TCRgamma, whereas the shorter
      alternative reading frame encodes a 7-kDa protein with five leucine residues in
      heptad repeats followed by a basic region. Studies with specific antibodies
      against each protein product revealed that both prostate and breast cancer cells
      contain only the 7-kDa protein, which is located in the nucleus. We have named
      this protein TCRgamma alternate reading frame protein (TARP). These results
      demonstrate that an alternative protein product is encoded by the TCRgamma locus
      in cells other than T lymphocytes.

PMID- 10931944
TI  - Transgenic overexpression of caveolin-3 in skeletal muscle fibers induces a
      Duchenne-like muscular dystrophy phenotype.
AB  - It recently was reported that Duchenne muscular dystrophy (DMD) patients and mdx
      mice have elevated levels of caveolin-3 expression in their skeletal muscle.
      However, it remains unknown whether increased caveolin-3 levels in DMD patients
      contribute to the pathogenesis of DMD. Here, using a genetic approach, we test
      this hypothesis directly by overexpressing wild-type caveolin-3 as a transgene in
      mice. Analysis of skeletal muscle tissue from caveolin-3- overexpressing
      transgenic mice reveals: (i) a dramatic increase in the number of sarcolemmal
      muscle cell caveolae; (ii) a preponderance of hypertrophic, necrotic, and
      immature/regenerating skeletal muscle fibers with characteristic central nuclei;
      and (iii) down-regulation of dystrophin and beta-dystroglycan protein expression.
      In addition, these mice show elevated serum creatine kinase levels, consistent
      with the myo-necrosis observed morphologically. The Duchenne-like phenotype of
      caveolin-3 transgenic mice will provide an important mouse model for
      understanding the pathogenesis of DMD in humans.

PMID- 10931947
TI  - Requirement for either a host- or pectin-induced pectate lyase for infection of
      Pisum sativum by Nectria hematococca.
AB  - Fungal pathogens usually have multiple genes that encode extracellular hydrolytic
      enzymes that may degrade the physical barriers in their hosts during the invasion
      process. Nectria hematococca, a plant pathogen, has two inducible pectate lyase
      (PL) genes (pel) encoding PL that can help degrade the carbohydrate barrier in
      the host. pelA is induced by pectin, whereas pelD is induced only in planta. We
      show that the disruption of either the pelA or pelD genes alone causes no
      detectable decrease in virulence. Disruption of both pelA and pelD drastically
      reduces virulence. Complementation of the double disruptant with pelD gene, or
      supplementation of the infection droplets of the double disruptant with either
      purified enzyme, PLA, or PLD, caused a recovery in virulence. These results show
      that PL is a virulence factor. Thus, we demonstrate that disruption of all
      functionally redundant genes is required to demonstrate the role of host barrier
      degrading enzymes in pathogenesis and that dismissal of the role of such enzymes
      based on the effects of single-gene disruption may be premature.

PMID- 10931946
TI  - Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and
      full-length cDNA cloning.
AB  - The primary neuroendocrine interface, hypothalamus and pituitary, together with
      adrenals, constitute the major axis responsible for the maintenance of
      homeostasis and the response to the perturbations in the environment. The gene
      expression profiling in the human hypothalamus-pituitary-adrenal axis was
      catalogued by generating a large amount of expressed sequence tags (ESTs),
      followed by bioinformatics analysis (http://www.chgc.sh.cn/ database). Totally,
      25,973 sequences of good quality were obtained from 31,130 clones (83.4%) from
      cDNA libraries of the hypothalamus, pituitary, and adrenal glands. After
      eliminating 5,347 sequences corresponding to repetitive elements and mtDNA,
      20,626 ESTs could be assembled into 9, 175 clusters (3,979, 3,074, and 4,116
      clusters in hypothalamus, pituitary, and adrenal glands, respectively) when
      overlapping ESTs were integrated. Of these clusters, 2,777 (30.3%) corresponded
      to known genes, 4,165 (44.8%) to dbESTs, and 2,233 (24.3%) to novel ESTs. The
      gene expression profiles reflected well the functional characteristics of the
      three levels in the hypothalamus-pituitary-adrenal axis, because most of the 20
      genes with highest expression showed statistical difference in terms of tissue
      distribution, including a group of tissue-specific functional markers. Meanwhile,
      some findings were made with regard to the physiology of the axis, and 200 full
      length cDNAs of novel genes were cloned and sequenced. All of these data may
      contribute to the understanding of the neuroendocrine regulation of human life.

PMID- 10931948
TI  - The E23 early gene of Drosophila encodes an ecdysone-inducible ATP-binding
      cassette transporter capable of repressing ecdysone-mediated gene activation.
AB  - At the onset of Drosophila metamorphosis, the steroid hormone 20-OH ecdysone
      directly induces a small number of early puffs in the polytene chromosomes of the
      larval salivary gland. Proteins encoded by the early genes corresponding to these
      transcriptional puffs then regulate the activity of both the early puffs
      themselves and a much larger set of late puffs. Three of these early genes encode
      transcription factors that play critical regulatory roles during metamorphosis.
      Here we report the cloning, DNA sequence, genomic structure, ecdysone
      inducibility, and temporal expression of an early gene residing in the 23E early
      puff and denoted E23 (Early gene at 23). In contrast to other early genes, E23
      encodes a protein with similarity to ATP-binding cassette transporters. Using
      heat shock-inducible transgenes, we found that E23 overexpression not only
      produces phenotypic abnormalities and lethality, but also interferes with
      ecdysone-mediated gene activation, demonstrating that E23 is capable of
      modulating the ecdysone response. Our results suggest the existence of a
      previously unrecognized regulatory mechanism for modulating steroid hormone
      signaling in Drosophila.

PMID- 10931949
TI  - Altered expression of expansin modulates leaf growth and pedicel abscission in
      Arabidopsis thaliana.
AB  - Expansins are cell-wall-loosening proteins that induce stress relaxation and
      extension of plant cell walls. To evaluate their hypothesized role in cell
      growth, we genetically manipulated expansin gene expression in Arabidopsis
      thaliana and assessed the consequent changes in growth and cell-wall properties.
      Various combinations of promoters were used to drive antisense and sense
      sequences of AtEXP10, which is maximally expressed in the growing leaf and at the
      base of the pedicel. Compared with controls, antisense lines had smaller rosettes
      because of shorter petioles and leaf blades and often acquired a twisted leaf
      morphology. Petiole cells from antisense plants were smaller than controls and
      their cell walls were significantly less extensible in vitro. Sense plants had
      slightly longer petioles, larger leaf blades, and larger cells than controls.
      Abscission at the base of the pedicel, where AtEXP10 is endogenously expressed,
      was enhanced in sense plants but reduced in antisense lines. These results
      support the concept that expansins function endogenously as cell-wall-loosening
      agents and indicate that expansins have versatile developmental roles that
      include control of organ size, morphology, and abscission.

PMID- 10931950
TI  - Blockade of the epidermal growth factor receptor tyrosine kinase suppresses
      tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice.
AB  - Overexpression of ErbB-2/Neu has been causally associated with mammary epithelial
      transformation. Here we report that blockade of the epidermal growth factor
      receptor (EGFR) kinase with AG-1478 markedly delays breast tumor formation in
      mouse mammary tumor virus (MMTV)/Neu + MMTV/transforming growth factor alpha
      bigenic mice. This delay was associated with inhibition of EGFR and Neu
      signaling, reduction of cyclin-dependent kinase 2 (Cdk2) and mitogen-activated
      protein kinase (MAPK) activities and cyclin D1, and an increase in the levels of
      the Cdk inhibitor p27(Kip1). In addition, BrdUrd incorporation into tumor cell
      nuclei was prevented with no signs of tumor cell apoptosis. These observations
      prompted us to investigate the stability of p27. Recombinant p27 was degraded
      rapidly in vitro by untreated but not by AG-1478-treated tumor lysates.
      Proteasome depletion of the tumor lysates, addition of the specific MEK1/2
      inhibitor U-0126, or a T187A mutation in recombinant p27 all prevented p27
      degradation. Cdk2 and MAPK precipitates from untreated tumor lysates
      phosphorylated recombinant wild-type p27 but not the T187A mutant in vitro. Cdk2
      and MAPK precipitates from AG-1478-treated tumors were unable to phosphorylate
      p27 in vitro. These data suggest that increased signaling by ErbB receptors up
      regulates MAPK activity, which, in turn, phosphorylates and destabilizes p27,
      thus contributing to dysregulated cell cycle progression.

PMID- 10931951
TI  - Silent synapses in the developing hippocampus: lack of functional AMPA receptors
      or low probability of glutamate release?
AB  - At early developmental stages, silent synapses have been commonly found in
      different brain areas. These synapses are called silent because they do not
      respond at rest but are functional at positive membrane potentials. A widely
      accepted interpretation is that N-methyl-d-aspartate (NMDA) but not alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are functionally
      expressed on the subsynaptic membrane. Here we show that, in both CA3 and CA1
      hippocampal regions, AMPA-mediated synaptic responses can be detected already at
      early stages of postnatal development. However, some synapses appear silent
      because of a very low probability of glutamate release. They can be converted
      into functional ones by factors that enhance release probability such as paired
      pulse stimulation, increasing the temperature or cyclothiazide (CTZ), a drug that
      blocks AMPA receptor desensitization and increases transmitter release.
      Conversely, conducting synapses can be switched off by increasing the frequency
      of stimulation. Although we cannot exclude that "latent AMPA receptors" can
      become functional after activity-dependent processes, our results clearly
      indicate that, in the neonatal hippocampus, a proportion of glutamatergic
      synaptic connections are presynaptically rather than postsynaptically silent.

PMID- 10931953
TI  - Scan statistics to scan markers for susceptibility genes.
AB  - Scan statistics are applied to combine information on multiple contiguous genetic
      markers used in a genome screen for susceptibility loci. This information may be,
      for example, allele sharing proportions for sib pairs or logarithm of odds (lod)
      scores in general small families. We focus on a dichotomous outcome variable, for
      example, case and control individuals or affected-affected versus affected
      unaffected siblings, and suitable single-marker statistics. A significant scan
      statistic based on the single-marker statistics represents evidence of the
      presence of a susceptibility gene. For a given length of the scan statistic, we
      assess its significance by Monte Carlo permutation tests. Comparing P values for
      varying lengths of scan statistics, we treat the smallest observed P value as our
      statistic of interest and determine its overall significance level. We applied
      this method to a genome screen with autism families. The result was informative
      and surprising: A susceptibility region was found (genome-wide significance
      level, P = 0.038), which is missed with conventional approaches.

PMID- 10931952
TI  - Genomewide insertional mutagenesis in Streptomyces coelicolor reveals additional
      genes involved in morphological differentiation.
AB  - The filamentous soil bacterium Streptomyces coelicolor undergoes a complex cycle
      of morphological differentiation involving the formation of an aerial mycelium
      and the production of pigmented antibiotics. We have developed a procedure for
      generating insertional mutants of S. coelicolor based on in vitro transposition
      of a plasmid library of cloned S. coelicolor DNAs. The insertionally mutated
      library was introduced into S. coelicolor, and transposon insertions were
      recovered at widely scattered locations around the chromosome. Many of the
      insertions revealed previously uncharacterized genes, and several caused novel
      mutant phenotypes, such as altered pigment production, enhanced antibiotic
      sensitivity, delayed or impaired formation of aerial hyphae, and a block in spore
      formation. The sporulation mutant harbored an insertion in one of three adjacent
      genes that are apparently unique to Streptomyces but are each represented by at
      least 20 paralogs at dispersed locations in the chromosome. Individual members of
      the three families often are found grouped together in a characteristic
      arrangement, suggesting that they have a common function.

PMID- 10931954
TI  - Functional MRI at 1.5 tesla: a comparison of the blood oxygenation level
      dependent signal and electrophysiology.
AB  - How well does the functional MRI (fMRI) signal reflect underlying
      electrophysiology? Despite the ubiquity of the technique, this question has yet
      to be adequately answered. Therefore, we have compared cortical maps generated
      based on the indirect blood oxygenation level-dependent signal of fMRI with maps
      from microelectrode recording techniques, which directly measure neural activity.
      Identical somatosensory stimuli were used in both sets of experiments in the same
      anesthetized macaque monkeys. Our results demonstrate that fMRI can be used to
      determine the topographic organization of cortical fields with 55% concordance to
      electrophysiological maps. The variance in the location of fMRI activation was
      greatest in the plane perpendicular to local vessels. An appreciation of the
      limitations of fMRI improves our ability to use it effectively to study cortical
      organization.

PMID- 10931955
TI  - Action potentials reliably invade axonal arbors of rat neocortical neurons.
AB  - Neocortical pyramidal neurons have extensive axonal arborizations that make
      thousands of synapses. Action potentials can invade these arbors and cause
      calcium influx that is required for neurotransmitter release and excitation of
      postsynaptic targets. Thus, the regulation of action potential invasion in axonal
      branches might shape the spread of excitation in cortical neural networks. To
      measure the reliability and extent of action potential invasion into axonal
      arbors, we have used two-photon excitation laser scanning microscopy to directly
      image action-potential-mediated calcium influx in single varicosities of layer
      2/3 pyramidal neurons in acute brain slices. Our data show that single action
      potentials or bursts of action potentials reliably invade axonal arbors over a
      range of developmental ages (postnatal 10-24 days) and temperatures (24 degrees C
      30 degrees C). Hyperpolarizing current steps preceding action potential
      initiation, protocols that had previously been observed to produce failures of
      action potential propagation in cultured preparations, were ineffective in
      modulating the spread of action potentials in acute slices. Our data show that
      action potentials reliably invade the axonal arbors of neocortical pyramidal
      neurons. Failures in synaptic transmission must therefore originate downstream of
      action potential invasion. We also explored the function of modulators that
      inhibit presynaptic calcium influx. Consistent with previous studies, we find
      that adenosine reduces action-potential-mediated calcium influx in presynaptic
      terminals. This reduction was observed in all terminals tested, suggesting that
      some modulatory systems are expressed homogeneously in most terminals of the same
      neuron.

PMID- 10931956
TI  - Evidence of nonspecific surface interactions between laser-polarized xenon and
      myoglobin in solution.
AB  - The high sensitivity of the magnetic resonance properties of xenon to its local
      chemical environment and the large (129)Xe NMR signals attainable through optical
      pumping have motivated the use of xenon as a probe of macromolecular structure
      and dynamics. In the present work, we report evidence for nonspecific
      interactions between xenon and the exterior of myoglobin in aqueous solution, in
      addition to a previously reported internal binding interaction. (129)Xe chemical
      shift measurements in denatured myoglobin solutions and under native conditions
      with varying xenon concentrations confirm the presence of nonspecific
      interactions. Titration data are modeled quantitatively with treatment of the
      nonspecific interactions as weak binding sites. Using laser-polarized xenon to
      measure (129)Xe spin-lattice relaxation times (T(1)), we observed a shorter T(1)
      in the presence of 1 mM denatured apomyoglobin in 6 M deuterated urea (T(1) = 59
      +/- 1 s) compared with that in 6 M deuterated urea alone (T(1) = 291 +/- 2 s),
      suggesting that nonspecific xenon-protein interactions can enhance (129)Xe
      relaxation. An even shorter T(1) was measured in 1 mM apomyoglobin in D(2)O (T(1)
      = 15 +/- 0.3 s), compared with that in D(2)O alone (T(1) = 506 +/- 5 s). This
      difference in relaxation efficiency likely results from couplings between laser
      polarized xenon and protons in the binding cavity of apomyoglobin that may permit
      the transfer of polarization between these nuclei via the nuclear Overhauser
      effect.

PMID- 10931957
TI  - Polyphosphate kinase is essential for biofilm development, quorum sensing, and
      virulence of Pseudomonas aeruginosa.
AB  - The human opportunistic pathogen Pseudomonas aeruginosa causes a variety of
      infections in immunocompromised hosts and in individuals with cystic fibrosis. A
      knockout mutation in the polyphosphate kinase (ppk) gene, encoding PPK
      responsible for the synthesis of inorganic polyphosphate from ATP, renders P.
      aeruginosa cells unable to form a thick and differentiated biofilm. The mutant is
      aberrant in quorum sensing and responses in that production of the quorum-sensing
      controlled virulence factors elastase and rhamnolipid are severely reduced. In a
      burned-mouse pathogenesis model, the virulence of the mutant is greatly reduced
      with severe defects in the colonization of mouse tissues. The conservation of PPK
      among many bacterial pathogens and its absence in eukaryotes suggest that PPK
      might be an attractive target for antimicrobial drugs.

PMID- 10931958
TI  - A retroviral RNA kissing complex containing only two G.C base pairs.
AB  - The dimerization of viral RNA through noncovalent interactions at their 5' ends
      is a key step in the life cycle of retroviruses. In Moloney murine leukemia
      virus, three stem-loops are important in this process. One is a self
      complementary tetraloop (H1), but the other two stem-loops (H2, H3) contain
      highly conserved GACG tetraloops that are not self-complementary sequences. Using
      two-dimensional NMR, we determined the structure of the H3 stem-loop.
      Surprisingly, it forms a stable, homodimeric kissing complex through only two
      intermolecular G small middle dotC base pairs. Cross-strand interactions of the
      adenines adjacent to the intermolecular G small middle dotC base pairs, plus
      unusual strong electrostatic interactions around the base pairs, contribute to
      the unexpected stability. This structure shows how even stem-loops without self
      complementary sequences can facilitate the intermolecular recognition between two
      identical RNAs, and thus initiate dimerization and encapsidation of retroviral
      RNAs.

PMID- 10931959
TI  - Ultrahigh-resolution multicolor colocalization of single fluorescent probes.
AB  - An optical ruler based on ultrahigh-resolution colocalization of single
      fluorescent probes is described in this paper. It relies on the use of two unique
      families of fluorophores, namely energy-transfer fluorescent beads
      (TransFluoSpheres) and semiconductor nanocrystal quantum dots, that can be
      excited by a single laser wavelength but emit at different wavelengths. A
      multicolor sample-scanning confocal microscope was constructed that allows one to
      image each fluorescent light emitter, free of chromatic aberrations, by scanning
      the sample with nanometer scale steps with a piezo-scanner. The resulting spots
      are accurately localized by fitting them to the known shape of the excitation
      point-spread function of the microscope. We present results of two-dimensional
      colocalization of TransFluoSpheres (40 nm in diameter) and of nanocrystals (3-10
      nm in diameter) and demonstrate distance-measurement accuracy of better than 10
      nm using conventional far-field optics. This ruler bridges the gap between
      fluorescence resonance energy transfer, near- and far-field imaging, spanning a
      range of a few nanometers to tens of micrometers.

PMID- 10931961
TI  - Synthesis of organs: in vitro or in vivo?

PMID- 10931960
TI  - The virulence factor AvrXa7 of Xanthomonas oryzae pv. oryzae is a type III
      secretion pathway-dependent nuclear-localized double-stranded DNA-binding
      protein.
AB  - AvrXa7 is a member of the avrBs3 avirulence gene family, which encodes proteins
      targeted to plant cells by a type III secretion apparatus. AvrXa7, the product of
      avrXa7, is also a virulence factor in strain PXO86 of Xanthomonas oryzae pv.
      oryzae. Avirulence and virulence specificities are associated with the central
      repeat domain, which, in avrXa7, consists of 25.5 direct repeat units. Mutations
      in three C-terminal nuclear localization signal motifs eliminated avirulence and
      virulence activities in rice and severely reduced nuclear localization in a yeast
      assay system. Both pathogenicity functions and nuclear localization were restored
      on the addition of the sequence for the nuclear localization signal motif from
      SV40 T-antigen. The loss of avirulence activity because of mutations in the
      acidic transcriptional activation domain was restored by addition of the
      activation domain from the herpes simplex viral protein VP16. The activation
      domain was also required for virulence activity. However, the VP16 domain could
      not substitute for the endogenous domain in virulence assays. In gel shift
      assays, AvrXa7 bound double-stranded DNA with a preference for dA/dT rich
      sequences. The results indicate that products of the avrBs3-related genes are
      virulence factors targeted to host cell nuclei and have the potential to interact
      with the host DNA and transcriptional machinery as part of their mode of action.
      The results also suggest that the host defensive recognition mechanisms are
      targeted to the virulence factor site of action.

PMID- 10931962
TI  - Immunoactive cannabinoids: therapeutic prospects for marijuana constituents.

PMID- 10931971
TI  - The beta-cell K(ATP) channel.

PMID- 10931972
TI  - Variations of intracellular pH in human erythrocytes via K(+)(Na(+))/H(+)
      exchange under low ionic strength conditions.
AB  - The change of intracellular pH of erythrocytes under different experimental
      conditions was investigated using the pH-sensitive fluorescent dye BCECF and
      correlated with (ouabain + bumetanide + EGTA)-insensitive K(+) efflux and Cl(-)
      loss. When human erythrocytes were suspended in a physiological NaCl solution
      (pH(o) = 7.4), the measured pH(i) was 7.19 + or - 0.04 and remained constant for
      30 min. When erythrocytes were transferred into a low ionic strength (LIS)
      solution, an immediate alkalinization increased the pH(i) to 7.70 + or - 0.15,
      which was followed by a slower cell acidification. The alkalinization of cells in
      LIS media was ascribed to a band 3 mediated effect since a rapid loss of
      approximately 80% of intracellular Cl(-) content was observed, which was
      sensitive to known anion transport inhibitors. In the case of cellular
      acidification, a comparison of the calculated H(+) influx with the measured
      unidirectional K(+) efflux at different extracellular ionic strengths showed a
      correlation with a nearly 1:1 stoichiometry. Both fluxes were enhanced by
      decreasing the ionic strength of the solution resulting in a H(+) influx and a
      K(+) efflux in LIS solution of 108.2 + or - 20.4 mmol (l(cells) hr)(-1) and 98.7
      + or - 19.3 mmol (l(cells) hr)(-1), respectively. For bovine and porcine
      erythrocytes, in LIS media, H(+) influx and K(+) efflux were of comparable
      magnitude, but only about 10% of the fluxes observed in human erythrocytes under
      LIS conditions. Quinacrine, a known inhibitor of the mitochondrial
      K(+)(Na(+))/H(+) exchanger, inhibited the K(+) efflux in LIS solution by about
      80%. Our results provide evidence for the existence of a K(+)(Na(+))/H(+)
      exchanger in the human erythrocyte membrane.

PMID- 10931973
TI  - Evidence for basolateral but not apical membrane localization of outwardly
      rectifying depolarization-induced Cl(-) channel in airway epithelia.
AB  - The rat primary cultured-airway monolayer had been an excellent model for
      deciphering the ion channel after nystatin permeabilization of its basolateral or
      apical membrane (Hwang et al., 1996). After apical membrane permeabilization of
      rat primary cultured-airway monolayer, 4,4'-diisothiocyanatostilbene-2, 2'
      disulfonic acid (DIDS)-sensitive outwardly rectifying depolarization-induced Cl(
      ) (BORDIC) currents were observed across the basolateral membrane in symmetrical
      NMG-Cl solution in this study. No significant Cl(-) current induced by the
      application of voltage clamping was observed across the apical membrane in
      symmetrical NMG-Cl solution after basolateral membrane permeabilization. The
      halide permeability sequence for BORDIC current was Br(-) = I(-) > Cl(-). BORDIC
      current was not affected by basolaterally applied bumetanide (0.5 mm).
      Basolateral DIDS (0.2 mm) but not apical DIDS inhibited CFTR mediated short
      circuit current (I(sc)) in an intact monolayer of rat airway epithelia, a T84
      human colonal epithelial cell line, and a Calu-3 human airway epithelial cell
      line. This is the first report showing that depolarization induced Cl(-) current
      is present on the basolateral membrane of airway epithelia.

PMID- 10931974
TI  - Mechanisms of action of rabbit CAP18 on monolayers and liposomes made from
      endotoxins or phospholipids.
AB  - We have investigated the mechanism of action of the cationic antimicrobial
      protein (18 kDa) CAP18 on liposomes and monolayers made from phospholipids and
      enterobacterial lipopolysaccharides (LPS). CAP18 intercalates into lipid matrices
      composed of LPS from sensitive strains, weaker into those made of LPS from a
      resistant strain (Proteus mirabilis strain R45) or negatively charged
      phospholipids, but not into those composed of neutral phosphatidylcholine. From
      the combination of data obtained with fluorescence resonance energy transfer and
      Fourier-transform infrared spectroscopy and film balance measurements, it can be
      concluded that structural differences in the LPS determine the depth of
      intercalation of CAP18 into the respective lipid matrices. Thus, we identified
      the L-Arap4N linked to the first Kdo of the LPS of P. mirabilis strain R45 to be
      responsible for the CAP18 resistance of this strain. These data provide insight
      into CAP18-mediated effects on the integrity of the outer membrane of Gram
      negative bacteria and led to an improved model for rabbit CAP18 membrane
      interaction.

PMID- 10931975
TI  - "Frustrated Exocytosis"--a novel phenomenon: membrane fusion without contents
      release, followed by detachment and reattachment of dense core vesicles in
      Paramecium cells.
AB  - The lipophilic fluorescent dye, FM1-43, as now frequently used to stain cell
      membranes and to monitor exo-endocytosis and membrane recycling, induces a
      cortical [Ca(2+)](i) transient and exocytosis of dense core vesicles
      ("trichocysts") in Paramecium cells, when applied at usual concentrations (</=10
      microm) in presence of extracellular Ca(2+) ([Ca(2+)](o) = 50 microm). When
      [Ca(2+)](o) is kept at 30 nm (<[Ca(2+)](rest)(i)), in about one third of the
      population of extrudable trichocysts docked at the cell membrane, FM1-43 induces
      membrane fusion, visible by FM1-43 fluorescence of the vesicle membrane. However,
      in this system extrusion of secretory contents cannot occur in absence of any
      sufficient Ca(2+)(o). Upon readdition of Ca(2+)(o) or some other appropriate
      Me(2+)(o) at 90 microm, secretory contents can be released (complete exocytosis).
      Resulting ghosts formed in presence of Ca(2+), Sr(2+) or Mn(2+) are vesicular,
      but when formed in presence of Mg(2+), for reasons to be elucidated, they are
      tubular, though both types are endocytosed and lose their FM1-43 stain. In
      contrast, in presence of [Mg(2+)](o) = 3 mm (which inhibits contents release),
      the exocytotic openings reseal and intact trichocysts with labeled membranes and
      with still condensed contents are detached from the cell surface ("frustrated
      exocytosis") within approximately 15 min. They undergo cytoplasmic streaming and
      saltatory redocking, with a half-time of approximately 35 min. During this time,
      the population of redocked trichocysts amenable to exocytosis upon a second
      stimulus increases with a half-time of approximately 35 min. Therefore,
      acquirement of competence for exocytotic membrane fusion may occur with only a
      small delay after docking, and this maturation process may last only a short
      time. A similar number of trichocysts can be detached by merely increasing
      [Mg(2+)](o) to 3 mm, or by application of the anti-calmodulin drug, R24517
      (calmidazolium). Essentially we show (i) requirement of calmodulin and
      appropriate [Me(2+)] to maintain docking sites in a functional state, (ii)
      requirement of Ca(2+)(o) or of some other Me(2+)(o) to drive membrane resealing
      during exo-endocytosis, (iii) requirement of an "empty" signal to go to the
      regular endocytotic pathway (with fading fluorescence), and (iv) occurrence of a
      "filled" signal for trichocysts to undergo detachment and redocking (with
      fluorescence) after "frustrated exocytosis".

PMID- 10931977
TI  - MR imaging of cirrhosis and its complications.

PMID- 10931976
TI  - Functional expression of the murine connexin 36 gene coding for a neuron-specific
      gap junctional protein.
AB  - The mouse connexin 36 (Cx36) gene was mapped on chromosome 2 and an identical
      transcriptional start site was determined in brain and retina on exon I. Rabbit
      polyclonal antibodies to the presumptive cytoplasmic loop of the Cx36 protein
      recognized in immunohistochemical analyses Cx36 expression in the retina,
      olfactory bulb, hippocampus, inferior olive and cerebellum. In olivary neurons
      strong punctate labeling at dendritic cell contacts and weaker labeling in the
      cytoplasm of dendrites were shown by immuno electron microscopy. After expression
      of mouse Cx36 cDNA in human HeLa cells, neurobiotin transfer was increased 1.8
      fold and electrical conductance at least 15-fold compared to untransfected HeLa
      cells. No Lucifer Yellow transfer was detected in either untransfected or Cx36
      transfected HeLa cells. Single Cx36 channels in transfected HeLa cells showed a
      unitary conductance of 14.3 + or - 0. 8 pS. The sensitivity of Cx36 channels to
      transjunctional voltage was low in both HeLa-Cx36 cells and Xenopus oocytes
      expressing mouse Cx36. No increased transfer of neurobiotin was detected in
      heterotypic gap junctions formed by Cx36 and 9 other connexins expressed in HeLa
      cells. Our results suggest that Cx36 channels function as electrical synapses for
      transmission of electrical and metabolic signals between neurons in the central
      nervous system.

PMID- 10931978
TI  - Hepatic morphologic changes in cirrhosis: MR imaging findings.

PMID- 10931979
TI  - Portosystemic collaterals of the upper abdomen: review of anatomy and
      demonstration on MR imaging.

PMID- 10931980
TI  - MR imaging of cirrhotic nodules.

PMID- 10931981
TI  - Transjugular liver biopsy: modified Ross transseptal needle versus quick-core
      biopsy needle.
AB  - BACKGROUND: We evaluated the differences in sample adequacy and safety between a
      transseptal needle and Quick-core biopsy needle for transjugular liver biopsy.
      METHODS: Eighteen consecutive patients who had a bleeding diatheses and/or
      ascites underwent transjugular liver biopsy using a transseptal needle (11
      patients) and Quick-core biopsy needle (seven patients). The length of the
      specimens was measured before fixation. A pathologist reviewed histologic slides
      for sample adequacy and pathologic diagnoses. Clinical records were reviewed for
      complication. RESULTS: In all patients, liver biopsy was successful. A total of
      45 specimens were obtained, with an average of 2.5 passes per patient. The length
      of specimen was significantly longer with the Quick-core biopsy needle than with
      the transseptal needle (p<0.05). Biopsied tissue was fragmented in 17 of 25
      specimens with the transseptal needle but not fragmented in any specimen with the
      Quick-core biopsy needle. All specimens were determined to be adequate except one
      with the transseptal needle. There was no early or delayed complication in any
      patient. CONCLUSION: Transjugular liver biopsy is a safe and effective procedure
      without any significant difference in complication and adequacy when using a
      transseptal needle or Quick-core biopsy needle. Larger specimens can be obtained
      without tissue fragmentation with the Quick-core biopsy needle.

PMID- 10931982
TI  - Benign regenerative nodules with copper accumulation in a case of chronic Budd
      Chiari syndrome: CT and MR findings.
AB  - Budd-Chiari syndrome is a rare disease characterized by hepatic outflow
      obstruction due to different causes. Hepatic nodules in patients with Budd-Chiari
      syndrome are rare and can be due to hepatocellular carcinoma and benign
      regenerative nodules. Imaging descriptions of regenerative nodules in cirrhotic
      livers are numerous, but the imaging findings of benign regenerative nodules
      associated with Budd-Chiari syndrome have only recently been reported. We present
      the computed tomographic and magnetic resonance features of benign regenerative
      hepatic nodules with copper accumulation in a patient with chronic Budd-Chiari
      syndrome.

PMID- 10931983
TI  - Intrahepatic peripheral cholangiocarcinoma: CT evaluation.
AB  - BACKGROUND: The purpose of our study was to evaluate the imaging features and
      patterns of contrast enhancement in peripheral cholangiocarcinomas with computed
      tomography (CT) and correlate these features with histologic findings when
      available. METHODS: We reviewed the CT scans of 24 patients with 25 peripheral
      cholangiocarcinomas proved by orthotopic liver transplantation (n = 1), liver
      resection (n = 7), percutaneous needle biopsy (n = 10), and fine needle
      aspiration biopsy (n = 6). Incremental dynamic nonhelical CT was performed in
      four cases and helical CT in 21 cases. Portal venous phase images were obtained
      in all 25 cases. Fourteen patients underwent helical CT during arterial and
      portal phases. Delayed images were obtained in 20 patients. RESULTS: The size of
      the tumors ranged from 1.2 to 17 cm. Bile duct dilatation was present in 13
      patients (52%), and regional lymph node enlargement was observed in six patients
      (24%). Retraction of the liver capsule was present in nine patients (36%). In
      eight patients (32%), satellite nodules were also detected. All tumors were
      globally hypodense during the portal phase. In 14 patients (70%), delayed images
      disclosed hyperattenuating tumors. Rimlike contrast enhancement was the most
      frequent pattern observed in either arterial (57% of patients) or portal (60% of
      patients) phase imaging. Portal venous encasement was seen in 10 patients (40%).
      CONCLUSION: In the proper clinical setting, detection of a hypodense hepatic
      lesion with peripheral enhancement, biliary dilatation, and contrast enhancement
      on delayed images are highly suggestive of peripheral intrahepatic
      cholangiocarcinoma.

PMID- 10931984
TI  - Hepatobronchial fistula due to transphrenic migration of hepatic echinococcosis:
      MR demonstration.
AB  - We present an uncommon case of hepatic hydatidosis, complicated by transphrenic
      migration of the cyst, in which the use of magnetic resonance performed with
      ultrafast, breath-hold, heavily T2-weighted sequences (HASTE) demonstrated a
      bronchial fistula.

PMID- 10931986
TI  - Choledochocele: diagnosis by magnetic resonance imaging.
AB  - The value of magnetic resonance imaging (MRI) and magnetic resonance
      cholangiopancreatography (MRCP) is demonstrated in a case of a 22-year-old female
      with a small choledochocele clinically presenting with acute cholecystitis and
      pancreatitis. Previous abdominal sonography and computed tomography were not
      diagnostic. MRI and MRCP showed a cystic dilatation of the distal common bile
      duct, intramurally located in the second portion of the duodenum and protruding
      into the duodenal lumen. These findings allowed a confident diagnosis of a
      choledochocele.

PMID- 10931985
TI  - Preoperative evaluation of Klatskin tumor: accuracy of spiral CT in determining
      vascular invasion as a sign of unresectability.
AB  - BACKGROUND: To assess the accuracy of spiral computed tomography (CT) in
      predicting the resectability of Klatskin tumor as determined by vascular
      invasion. METHODS: Twenty-one consecutive patients with Klatskin tumor who had
      undergone laparotomy were included in this study. The preoperative thin-section
      (5-mm-thick) spiral CT scans of these patients were assessed for the surgical
      resectability of tumor by evaluating the vascular invasion. The criterion for
      vascular invasion indicating unresectability was the tumoral invasion of the
      proper hepatic artery or main portal vein or simultaneous invasion of one side of
      the hepatic artery and the other side of the portal vein. RESULTS: All nine
      patients with tumors thought to be unresectable on the basis of CT findings had
      tumors that were unresectable at surgery (positive predictive value, 100%). Of 12
      patients with tumors thought to be resectable, six had resectable tumors
      (negative predictive value, 50%). Spiral CT failed to detect small hepatic
      metastasis (n = 1), lymph node metastasis (n = 1), extensive tumor (n = 2) and
      variation of bile duct (n = 2), which precluded surgical resection. CONCLUSION:
      Spiral CT is a reliable method for detecting vascular invasion and unresectable
      tumors. However, it has limitations in detecting variations of the bile duct or
      the intraductal extent of tumor.

PMID- 10931988
TI  - MR imaging of focal splenic extramedullary hematopoiesis in polycythemia vera:
      case report.
AB  - We report a case with focal mass-like lesion of the spleen in polycythemia vera.
      Magnetic resonance imaging of the lesion showed homogeneous hyperintensity on T2
      weighted images, with progressive enhancement on dynamic magnetic resonance
      images after bolus injection of gadolinium. The magnetic resonance features of
      focal splenic extramedullary hematopoiesis have not been previously reported.

PMID- 10931987
TI  - Influence of paramagnetic contrast on single-shot MRCP image quality.
AB  - To assess the ability of gadolinium enhancement to suppress the overlapping
      vessel signals that diminish the image quality of magnetic resonance
      cholangiopancreatography (MRCP), we obtained MRCP before and after intravenous
      injection of gadolinium. Signal intensity ratio of the common bile duct to the
      main pancreatic duct was significantly improved after the injection of contrast
      media. The image quality of the postcontrast MRCP was better than that of the
      precontrast one.

PMID- 10931989
TI  - Abdominal involvement in neurofibromatosis 1: sonographic findings.
AB  - BACKGROUND: Neurofibromatosis 1 (NF1) has been studied from many viewpoints, but
      its abdominal involvement has rarely been reported. Sonography (US) is now the
      initial diagnostic tool for abdominal exploration, which prompted us to determine
      the clinical manifestations and US findings of abdominal involvement in NF1.
      METHODS: We analyzed the US findings and clinical data of eight NF1 cases with
      abdominal involvement. RESULTS: Abdominal involvement included neurofibromatous
      tumor growth in the liver, mesentery, and retroperitoneum, in addition to
      mesenteric leiomyomatosis and gastric carcinoma. Color Doppler US was useful not
      only in detecting blood flows in the lesions but also in preventing hazardous
      vascular injury during tumor biopsy. CONCLUSION: A better understanding of the
      clinical manifestations and US findings of abdominal involvement in NF1
      translates into improved NF1 patient care.

PMID- 10931991
TI  - Enterolithiasis in Crohn's disease.
AB  - Enterolithiasis of the small bowel is unusual. Etiologic factors include stasis
      secondary to intestinal strictures or diverticula. There have been 19 reported
      cases of enteroliths associated with Crohn's disease and we report three
      additional patients. Enteroliths only occur in longstanding Crohn's disease and
      are important clues to the presence of underlying strictures; they may occur as a
      result of adenocarcinoma complicating Crohn's disease. The radiologic features of
      enteroliths are discussed.

PMID- 10931992
TI  - Eosinophilic ileocolitis secondary to Enterobius vermicularis: case report.
AB  - We describe an unusual presentation of Enterobius vermicularis infestation.
      Computed tomography showed wall thickening in the distal ileum and cecum, with
      fat stranding, ascites and mesenteric adenopathy. Fluoroscopic examination
      confirmed distal ileal transverse fold thickening. Isolation of Enterobius
      vermicularis in stool and biopsy confirmed the diagnosis. Enterobius should be
      included among the causes of eosinophilic ileocolitis.

PMID- 10931990
TI  - 3D CT angiography of the celiac and superior mesenteric arteries with
      multidetector CT data sets: preliminary observations.

PMID- 10931994
TI  - Cavernous hemangioma arising from the lesser omentum: MR findings.
AB  - We report the magnetic resonance findings of an unusual hemangioma in the lesser
      omentum. A well-circumscribed, large mass was identified between the stomach and
      the left lobe of the liver, with compression of adjacent liver parenchyma. The
      mass showed low signal intensity (SI) on T1-weighted images, high SI on T2
      weighted images with multiple septa, and slightly decreased SI on out-of-phase T1
      weighted images. After gadolinium contrast administration, septa within the mass
      showed minimal enhancement on 30-s T1-weighted images and mild enhancement on 5
      min T1-weighted images. The mass was histopathologically diagnosed as a cavernous
      hemangioma comprised of multiple vascular spaces, fibrotic tissue, and
      adipocytes.

PMID- 10931993
TI  - Preoperative assessment of local tumor extent in advanced rectal cancer: CT or
      high-resolution MRI?
AB  - BACKGROUND: We compared high-resolution magnetic resonance imaging (MRI) with
      computed tomography (CT) in the assessment of tumor infiltration in surrounding
      structures for locally advanced primary and recurrent rectal cancer. METHODS:
      Twenty-six patients with operable, locally advanced rectal cancer (15 recurrent
      and 11 primary) were evaluated with conventional pelvic CT and 1.5-T high
      resolution MRI with a quadrature phased-array coil. The images were scored for
      invasion of nine neighboring pelvic structures, and the results were compared
      with surgical and histologic findings. RESULTS: A total of 234 structures in 26
      patients was evaluated for tumor invasion. For MRI the, sensitivity was 97% and
      the specificity 98%; for CT, the sensitivity was 70% and the specificity was 85%.
      The difference in performance was statistically significant (p<0.001). The
      failure most frequently made on CT was the false-positive prediction of pelvic
      floor and piriform muscle invasion (14), whereas MRI showed only four false
      positive predictions. MRI correctly predicted all four cases of sacral bone
      invasion, three of which were missed by CT. MRI was accurate in 20 patients (80%)
      and CT in only five patients (19%). CONCLUSION: High-resolution MRI using a
      quadrature phased-array coil is highly accurate and superior to CT in predicting
      tumor infiltration in surrounding structures for locally advanced primary or
      recurrent rectal cancer and is recommended in the preoperative work-up of these
      tumors.

PMID- 10931995
TI  - Pedunculated exogastric leiomyoblastoma presenting as a wandering abdominal mass.
AB  - We report the imaging findings in a case of pedunculated exogastric
      leiomyoblastoma presenting as a wandering abdominal mass. Ultrasound and computed
      tomography showed a large, mixed solid and cystic mass in the peritoneal cavity.
      Computed tomography clearly showed that the mass was connected to the stomach by
      a narrow stalk. Small bowel follow-through showed subtle extrinsic indentation of
      the gastric body. The mass wandered from the right to the left side of the
      peritoneal cavity during various radiologic examinations.

PMID- 10931996
TI  - Chronic anisakiasis presenting as a mesenteric mass.
AB  - Chronic anisakiasis is a rare entity, and its diagnosis is difficult. We report a
      case of chronic anisakiasis with multiple gastrointestinal manifestations
      presenting as a palpable mesenteric mass, diagnosed by specific serology and
      histologic findings. We describe the computed tomographic appearance of this mass
      and the pathologic correlations. To our knowledge, this is the first time this
      mesenteric location has been detected by imaging before surgery.

PMID- 10931997
TI  - Mesenteric Castleman's disease: case report.
AB  - An asymptomatic case of hyaline vascular-type Castleman's disease localized to
      the mesentery and detected incidentally by ultrasound is presented. Computed
      tomographic, angiographic, and histologic findings are reported. This type of
      Castleman's disease predominates in the thorax and is very rare in the mesentery.

PMID- 10931998
TI  - Retroperitoneal liposarcoma: sonographic findings.
AB  - This study, based on sonographic (US) results of 10 cases with histologically
      proven retroperitoneal liposarcoma (eight well-differentiated and two pleomorphic
      types), shows that the presence of fine echogenic lines within the tumor is a
      useful sign for diagnosing a well-differentiated liposarcoma. Presence of
      numerous fine fibrous septa in the lipomatous tumor tissue is thought to be
      responsible for this interesting phenomenon. Of interest is the fact that the
      direction of these lines changed according to the probe format used: parallel
      horizontal lines when using a linear probe and concentric lines converging toward
      the probe when using a sector or curved linear probe. In contrast, pleomorphic
      liposarcoma does not show this US sign. Knowledge of these US findings is useful
      for the diagnosis of retroperitoneal liposarcoma.

PMID- 10932000
TI  - Abstracts of selected papers from the current literature

PMID- 10931999
TI  - Chronic tuberculous epididymitis: color Doppler US findings with histopathologic
      correlation.
AB  - BACKGROUND: The aim of this study was to determine the color Doppler features of
      tuberculous epididymitis and to correlate these findings with histopathologic
      findings. METHODS: Color Doppler ultrasound (US) findings of 12
      histopathologically proven tuberculous epididymitis and tuberculous epididymo
      orchitis in 11 consecutive patients were retrospectively analyzed. Color Doppler
      US findings of tuberculous epididymitis were correlated with histopathologic
      findings. RESULTS: Color Doppler US findings of tuberculous epididymitis
      demonstrated no blood flow in the epididymal lesions except for focal linear or
      spotty flow signals in the peripheral portion. These findings correlated well
      with pathologic findings; the central portion of the epididymal lesions
      demonstrated granulomas with caseation necrosis, and the peripheral portion of
      the epididymal lesions had several medium to small vessels. CONCLUSIONS: Color
      Doppler US may be helpful for differential diagnosis of tuberculous epididymitis
      and non-tuberculous epididymitis.

PMID- 10932001
TI  - [Molecular cloning of a novel gene located on chromosome 3p25.3 and an analysis
      of its expression in nasopharyngeal carcinoma].
AB  - OBJECTIVE: To obtain the novel genes associated with human nasopharyngeal
      carcinoma(NPC) on chromosome 3p24-26. METHODS: Twenty epithelial-derived
      expressed sequence tags(EST) were selected from chromosome 3p24-26 where loss of
      heterozygosity(LOH) frequently occurs in NPC tissues. Primers were designed based
      on the sequences of these ESTs. RT-PCR was used to amply their corresponding cDNA
      fragments from NPC cell line HNE1 and primary cultures of normal nasopharyngeal
      epithelial cells. The differential expression of two ESTs, T93093 and R41598, was
      confirmed by Northern blot. Then, expression of EST T93093 was further detected
      in 7 normal nasopharyngeal and 19 NPC biopsies. cDNA library screening was used
      to get its full cDNA sequence and the sequence of this novel gene was analyzed by
      bioinformatics. RESULTS: Thirteen ESTs(T62511, N39155, N68660, R61275, T95314,
      R06143, H52697, H66521, AA128685, AA284537, N52379, AA054180, and H98090) showed
      the similar expression level and 5 ESTs(R00732, R07573, R98052, H91759, H17566)
      showed no expression in both types of cells. EST T93093 was down-expressed,
      whereas EST R41598 up-expressed in NPC HNE1 cells. The EST T93093 was also found
      to be down-expressed in 26.3%(5/19) of NPC biopsies. The full length cDNA of this
      gene was obtained and named NAG-7, which is located at chromosome 3p25.3. Its
      1677 bp full length cDNA has a potential open reading frame(ORF) predicting a 94
      amino acid protein with a molecular weight of 11023.87 Dalton. Bioinformatics
      analysis of the NAG-7 gene shows that it is a transmembrane protein containing a
      protein kinase C(PKC) phosphorylation site and a myristyl site. It has no
      significant homology to any reported genes in database of GenBank(AF086709).
      CONCLUSION: NAG-7 is a novel gene down-expressed in NPC, which may be involved in
      the development of NPC.

PMID- 10932003
TI  - [TBX5 mutation in Chinese patients with Holt-Oram syndrome].
AB  - OBJECTIVE: To analyse TBX5 mutation in Chinese patients with Holt-Oram
      syndrome(HOS). METHODS: Seven HOS families were analysed with single strand
      conformation polymorphism(SSCP) and sequencing. RESULTS: Three SSCP changes were
      detected and identified as the TBX5 gene mutation at three new sites. One of the
      changes is a frameshift mutation caused by a base cytidine deletion at the cDNA
      sequence of 416, which altered all the codons after the point, thus it can not
      encode the protein of normal amino acid sequence; another is a missense mutation
      induced by a base substitution(C-->A) at the cDNA sequence of 145, which made the
      codon of that point change from CAG-->AAG, and encoded amino acid changed from
      glutamine(Gln) to lysine(Lys), consequently the change weakened the function of
      TBX5 protein; the third is also a missense mutation which resulted from a base
      substitution (T-->C) at the cDNA sequence of 161, this change made the codon of
      that point change from ATC-->ACC, it changed the encoded amino acid from
      isoleucine(Ile) to threonine(Thr), which reduced the function of TBX5 protein.
      CONCLUSION: HOS in Chinese is caused by mutation in TBX5.

PMID- 10932004
TI  - [Genetic polymorphisms of eight STR loci in a Chinese Han population].
AB  - OBJECTIVE: To understand the allele structure and genetic polymorphism at eight
      STR loci in Chinese Han population and construct a preliminary database. METHODS:
      EDTA-blood specimens were collected from the unrelated individuals in Chengdu,
      China. The DNA samples were extracted with Chelex method and were amplified by
      PCR technique. The PCR products were analyzed by the PAG horizontal
      electrophoresis with discontinuous buffer system and by the approach of the
      automated fluorescence detection. RESULTS: Five STR loci consist of simple repeat
      motifs, while three STR loci contain complex repeat structures. The STR
      polymorphisms at all of the eight loci have been observed in Chinese Han
      population. According to the obtained data, the combined exclusion probability
      and the combined discrimination power for these STR markers in Chinese population
      are 0.9978 and 0.999 999 992, respectively. CONCLUSION: The obtained data are
      beneficial to understanding the population genetics of the eight STR loci in
      Chinese Han population. For forensic genetics, the obtained data can be used to
      calculate the probabilities dealing with the paternity test and the individual
      identification.

PMID- 10932002
TI  - [Study on genetic mutations of the vWF in type 2A von Willebrand disease].
AB  - OBJECTIVE: To study the molecular pathological mechanism of the type 2A von
      Willebrand disease(vWD) and the relationship of the phenotypes with genotypes.
      METHODS: A total of 126 patients with the hereditary hemorrhagic disease were
      examined using bleeding time, vWF:Ag, FVIII:CAg, ristocentin induced platelet
      agglutination assay(RIPA) and multimer analysis of plasma. The exon 28 of
      authenticity vWF gene was studied by PCR, denaturing gradient gel
      electrophoresis(DGGE) and sequencing in the type 2A vWD. RESULTS: Fourteen cases
      were diagnosed as type 2A vWD. Four cases of point mutations resulting in single
      animo acid substitutions, Arg611His, Ala737Glu, Arg834Trp, were identified in 3
      families of type 2A vWD. Ala737Glu substitution in vWF is caused by a novel
      missense mutation. CONCLUSION: The molecular pathological mechanism of the type
      2A vWD is very variant.

PMID- 10932005
TI  - [Study of CFTR gene mutation in Chinese CUAVD patients].
AB  - OBJECTIVE: To analyze the frequency and hot spots of cystic fibrosis
      transmembrane conductance regulator(CFTR) gene in Chinese congenital unilateral
      absence of the vas deferens (CUAVD) patients. METHODS: The mutation of CFTR exons
      2, 3, 4, 5, 6a, 8, 10, 11, 12, 13, 15A, 17b, 19A, 20, 21, and 23 were detected.
      PCR-single strand conformation polymorphism(SSCP) and direct sequencing were
      performed on 15 cases of Chinese CUAVD. RESULTS: One case exhibited an abnormal
      shift SSCP band in exon 17b of CFTR gene and subsequent DNA sequencing showed C
      to A transversion at position 3295 that led to a predicted change of
      Leusine(codon 1055, CTT) to Isoleucine(codon ATT). CONCLUSION: CFTR mutation
      could be detected in Chinese CUAVD patients. The missense mutation, Leu1055Ile,
      was identified as a novel CFTR mutation. It is necessary that Chinese CUAVD
      patients and their wives should be screened for CFTR gene prior to
      intracytoplasmic sperm injection.

PMID- 10932006
TI  - [Study on interphase cytogenetic abnormalities in malignant cells in pleural
      fluids from lung cancer cases].
AB  - OBJECTIVE: To study the interphase cytogenetic abnormalities in malignant cells
      in pleural fluids from lung cancer cases by fluorescence in situ
      hybridization(FISH) and compare the result of FISH with that of conventional
      cytology. METHODS: Twenty-six pleural fluids from the lung cancer cases were
      detected by dual-fluorescence in situ hybridization centromere DNA probes of
      chromosomes 7, 11, 17, and X. RESULTS: In 19 positive pleural fluids the rates of
      hyperdiploid in chromosomes 7, X, 17 and 11 were 16(84.2%), 14(73. 7%), 12(63.2%)
      and 8(42.1%), respectively. In 2 suspicious malignant pleural fluids, both
      chromosomes 7 and X showed hyperdiploid. Two cases of hyperplasia from 5 negative
      specimens also showed gain of chromosome X. Another 3 negative pleural fluids had
      a normal number of chromosome. CONCLUSION: One of the important abnormalities
      occurred in tumor cells derived from pleural fluid of lung cancer is
      hyperdiploid, which can be detected by FISH. Therefore, hyperdiploid in pleural
      fluid cells can be an implication for the malignancy that has not been detected
      or confirmed by cytological examination.

PMID- 10932007
TI  - [Polymorphisms of four STRs and their associations with IDDM in Chinese Han
      population].
AB  - OBJECTIVE: To obtain the polymorphic data of short tandem repeat(STR) loci of
      D15S657, D11S1369, D6S2420 and D6S503 in Chinese Han population and to study the
      association of these four STR loci with insulin-dependent diabetes
      mellitus(IDDM). METHODS: The polymorphisms of the four STRs were studied by
      polymerase chain reaction-polyacrylamide gel electrophoresis(PCR-PAGE) followed
      by direct sequencing of PCR products in 105 normal Chinese Hans and 48 patients
      with IDDM. RESULTS: Seven alleles at D15S657 locus, 5 alleles at D11S1369 locus,
      7 alleles at D6S2420 locus and 4 alleles at D6S503 locus were found. No deviation
      from Hardy-Weinberg equilibrium was observed. The heterozygosities of these loci
      were 0. 7524, 0.6000, 0.6286, 0.6571 and the polymorphic information
      contents(PIC) 0.7616, 0.4430, 0.5345 and 0.5932, respectively. The allele
      frequencies of allele A(5) at D15S657 locus, allele A(5) at D11S1369 locus and
      allele A(4) at D6S2420 locus were increased significantly in patients with IDDM,
      compared to those in the control group. CONCLUSION: The four STRs, used as
      genetic markers, were suitable for case-control study, forensic medicine
      identification and population genetic study. There is an association between the
      polymorphisms of D15S657, D11S1369, D6S2420 and IDDM.

PMID- 10932008
TI  - [Differentiation of achondroplasia and other similar genetic dwarfism by FGFR3
      gene analysis].
AB  - OBJECTIVE: To study the gene mutation of Chinese patients with
      achondroplasia(ACH) and to set up a simple and rapid molecular diagnostic method
      to differentiate ACH from other similar genetic dwarfism. METHODS: The specific
      fragment of fibroblast growth factor receptor 3(FGFR3) transmembrane domain was
      amplified from dried blood spots of 21 patients with ACH and 6 suspicious
      patients with ACH by polymerase chain reaction, then mutation was screened and
      detected by restrictive enzyme analysis, single strand conformation
      polymorphism(SSCP) and denaturing gradient gel electrophoresis(DGGE). RESULTS:
      One out of 6 suspicious cases was ACH and 5 were pseudoachondroplasia(PSACH).
      Twenty-one out of 22 patients with ACH bore a G to A transition at nucleotide
      1138 and 1 bore a G to C transversion at this same position. CONCLUSION: The
      nucleotide 1138 of FGFR3 gene is also the hotspot of mutation in Chinese patients
      with ACH. A simple and rapid molecular diagnostic method has been set up to
      differentiate ACH from other similar genetic dwarfism.

PMID- 10932009
TI  - [Association between hypertensive cerebrovascular stroke and renin-angiotensin
      system gene polymorphism from Chinese cohort in Shanghai].
AB  - OBJECTIVE: To evaluate the association between hypertensive cerebrovascular
      stroke and renin-angiotensin system gene polymorphism from Chinese cohort.
      METHODS: The polymorphisms of angiotensinogen(AGT) and angiotensin-converting
      enzyme(ACE) from 257 cases of simple essential hypertension(EH) and 218 cases of
      hypertensive stroke(131 hemorrhagic cases and 87 ischemic cases were detected by
      PCR-RFLP. RESULTS: The frequencies of DD genotype and D allele of ACE gene in
      ischemic stroke were significantly higher than those in hemorrhagic stroke and
      EH, and the odds ratios(OR) of DD/II genotype were 3.25(2.20-4.79) and 2.87(2.03
      4.06), while the OR of D/I allele were 1.83(1.38-2.43) and 1.69(1.27-2.24)
      respectively. Otherwise, there was no difference in frequency distribution of
      Met235Thr mutation polymorphism and DD+TT/non DD non TT combined among the three
      groups. CONCLUSION: The I/D polymorphism of ACE gene may be one of the risk
      factors and susceptible genetic markers for ischemic stroke with essential
      hypertension in Chinese.

PMID- 10932010
TI  - [Cytochrome P450 1A1 and cytochrome P450 2E1 gene polymorphisms in Guangzhou
      Hans].
AB  - OBJECTIVE: To determine the distribution of cytochrome P450 1A1(CYP1A1) and
      cytochrome P450 2E1(CYP2E1) gene polymorphisms in Guangzhou Hans. METHODS: A
      total of 150 healthy Guangzhou Hans were studied with PCR-RFLP and ASA
      techniques. Current results were compared with the data on other ethnic groups.
      RESULTS: In the 150 individuals tested, the frequencies of the m1(Msp I-) and
      m2(Msp I+) alleles of the Msp I polymorphic site in the 3' non-coding region of
      the CYP1A1 gene were found to be 62.33% and 37.67%, respectively. The observed
      frequencies of the m1m1, m1m2 and m2m2 genotypes were found to be 40%, 44.67% and
      15.33%, respectively, which met Hardy-Weinberg equilibrium. The frequencies of
      the A and G alleles of the exon 7 A4889G polymorphic site in the CYP1A1 gene were
      found to be 79% and 21%, respectively. The observed frequencies of the AA, AG and
      GG genotypes were found to be 62.67%, 32.67% and 4.66%, respectively, which met
      Hardy-Weinberg equilibrium. A close linkage between the Msp I polymorphism and
      exon 7 A4889G polymorphism was observed in Guangzhou Hans(chi(2)=62.2358,
      P<0.005). The frequencies of the C1(Rsa I+, Pst I-) and C2(Rsa I-, Pst I+)
      alleles of the Rsa I polymorphic site in the 5' flanking region of the CYP2E1
      gene were found to be 85.3% and 14.7%, respectively. The observed frequencies of
      the C1C1, C1C2 and C2C2 genotypes were found to be 67.3%, 29.3%, and 3.4%,
      respectively, which met Hardy-Weinberg equilibrium. CONCLUSION: The frequencies
      of the CYP1A1 and CYP2E1 gene polymorphisms in Guangzhou Hans were similar to
      those in Japanese population, but were significantly different from those in
      European populations.

PMID- 10932011
TI  - [Transcriptional expression of apoptosis suppression gene bcl-2 in non-small cell
      lung carcinoma].
AB  - OBJECTIVE: To investigate the role of Bcl-2 gene in oncogenesis and progression
      of non-small cell lung carcinoma(NSCLC). METHODS: The mRNA expressions of Bcl-2
      gene in a series of 137 pulmonary tissues collected at various sites and with
      different properties were studied with Northern hybridization and non-radioactive
      digoxigenin labeling and detection system. RESULTS: According to the observations
      on benign lesions, non-cancer tissues distant from tumour, para-tumour tissues
      and cancer tissues, there was a tendency of mRNA expression increasing of Bcl-2
      gene. Among them, Bcl-2 mRNA expression in lung cancer tissues was significantly
      increased, compared with that in benign lesions and tissues distant from tumour
      (P<0.01). The Bcl-2 mRNA expression in lymph node with cancer metastasis was
      significantly higher than that in lymph node without cancer metastasis(P<0.05).
      The Bcl-2 mRNA expression was relative to cell differentiation of the cancer, but
      not to the histological classification. CONCLUSION: Over expression of Bcl-2 gene
      might be involved in the oncogenesis and metastasis of NSCLC.

PMID- 10932012
TI  - [Estrogen receptor gene polymorphism and its association with clinicopathological
      manifestation of lupus nephritis].
AB  - OBJECTIVE: To investigate the distribution of estrogen receptor (ER) in patients
      with lupus nephritis (LN), and the association between ER gene polymorphism and
      the clinical and pathological features of the disease. METHODS: The Pvu II and
      Xba I restriction fragment length polymorphism (RFLP) of estrogen receptor gene
      were analyzed in 245 biopsy proven LN patients (58 males and 187 females) and 172
      normal controls(101 males and 71 females) by PCR-RFLP. The clinical and
      pathological features of 49 male and 152 female LN patients with genotype PpXx or
      Ppxx, ppxx were then analyzed respectively. RESULTS: It was found that genotype
      PpXx and ppxx, Ppxx were three major genotypes of ER gene in both lupus patients
      group and control group. The distribution of ER gene polymorphism was quite
      different in lupus patients of different genders. The frequency of the PpXx
      genotype was significantly higher in male LN patients than in both the gender
      matched normal controls (P<0.05) and the female LN patients (P<0.05), while no
      difference was shown in the frequency of PpXx genotype between female LN patients
      and female controls. Interestingly, varied clinical and renal pathological
      features were also demonstrated in female patients with different genotypes of ER
      gene. CONCLUSION: The distribution of ER gene polymorphism in LN patients varies
      with gender. The PpXx genotype of ER gene may be associated with the
      susceptibility of LN in male. ER gene polymorphism is probably one of the genetic
      factors contributing to the development of clinical heterogeneity and sexually
      dimorphic manifestations of LN.

PMID- 10932014
TI  - [The application of fluorescence in situ hybridization performed on the
      decolorized G-banding chromosomes in detecting the marker chromosomes of gastric
      cancer].
AB  - OBJECTIVE: Using a rapid, accurate method that detects the marker chromosomes of
      gastric cancer and enhancing the ability of discriminating complicated chromosome
      rearrangements of gastric cancer. METHODS: The improved method of fluorescence in
      situ hybridization(FISH) performed on the decolorized G-banding chromosome was
      used. RESULTS: The changes of two marker chromosomes (M1, M2) of the cell
      line(SGC-7901) of gastric cancer and one marker chromosomes(M3) of one primary
      gastric cancer were respectively analyzed by this method. The M1, M2 and M3 had
      complicated structural chromosome aberrations: del(7)(p15)/del(7)(q22),
      t(1;3)(p11;q11) and del(7)(q32). CONCLUSION: This method showed strong signals,
      low backgrounds and well-repetitions. It may play an important part in exploring
      the chromosome rearrangements in the process of pathogenesis and development of
      gastric cancer.

PMID- 10932013
TI  - [Detection of fetal cells in maternal blood by fluorescence in situ
      hybridization].
AB  - OBJECTIVE: To isolate fetal nucleated cells from maternal blood and determine its
      fetal origin. METHODS: Enrichment and isolation of nucleated cells in maternal
      blood from 20 samples in the first trimester of pregnancy, 20 samples in the mid
      trimester of pregnancy, and 15 samples after delivery. Fluorescence in situ
      hybridization was performed using Y specific probe PY3.4 to identify fetal cells.
      RESULTS: Fifteen women in the first trimester and 15 women in the mid-trimester
      of pregnancy carried male fetuses. The rates of positive cells were 1:6528.0 and
      1:2783.8 respectively, and there was a highly significant difference when these
      rates were compared with the positive cells rate of the 10 female fetuses in the
      same trimesters. No significant difference in positive cells rate was found
      between 1 week after delivery and the mid-trimester of pregnancy, nor was it
      found between 3 months after delivery and the 10 samples of female fetuses in the
      same time. CONCLUSION: These data suggest that fetal cells can be detected as
      early as from 50 days of gestation in maternal blood, in the meantime, the rate
      of fetal cells will increase with gestational age. One week after delivery, fetal
      cells still exist, and 3 months after delivery, the fetal cells will no longer be
      detected.

PMID- 10932015
TI  - [Detection of epidermal growth factor receptor gene amplification in human
      laryngeal carcinomas by means of fluorescence in situ hybridization].
AB  - OBJECTIVE: To detect epidermal growth factor receptor(EGFR) gene amplification in
      human laryngeal carcinoma Hep-2 cell line and laryngeal carcinoma tissues.
      METHODS: The technique of fluorescence in situ hybridization(FISH). RESULTS: The
      EGFR gene amplification of a laryngeal carcinoma Hep-2 cell line and 5 laryngeal
      carcinoma tissues were detected by FISH. In the metaphase chromosome and
      interphase nuclei of Hep-2 cell line and 2 laryngeal carcinoma tissues, distinct
      cluster and multiple dot signals were found. In the interphase nuclei of the
      other 3 laryngeal carcinoma tissues, no increase in the number or extent of the
      hybrid signals was found. CONCLUSION: Compared with normal diploid cell, the EGFR
      gene amplification was observed at different levels ranging from 2 to 8 folds in
      metaphase chromosome and interphase nuclei of Hep-2 cell line and 2 laryngeal
      carcinoma tissues while no amplification was observed in the other 3 laryngeal
      carcinoma tissues. The results demonstrate that quantitative detection of
      amplified gene by FISH in the metaphase chromosome and interphase nuclei is
      useful for detection of laryngeal carcinoma tissues.

PMID- 10932016
TI  - [Detection of DNA strand breakage in human spermatozoa by use of single-cell gel
      electropheresis].
AB  - OBJECTIVE: To establish the single-cell gel electropherosis (SCGE) protocol for
      detection of DNA strand breakage in human spermatozoa. METHODS: The slides on
      which sperm cells and agarose were layered were immersed in a cold lysing
      solution of pH10 to lyse the sperm cells. Sperm nuclei were then pretreated with
      10 mmol/L of DTT for 1 h, 10 microg/ml of RNase A for 4 h and 200 microg/ml of
      proteinase K for 15 h. Lastly, electrophoresis was performed in electrophoresis
      running buffer(pH10) at 12V (0.46V/cm) and 100 mA for 1 h. Sperm nuclei were
      stained with 15 microg/ml of EtBr for 5 min. The percentage of comet cells was
      counted. The in vitro hydrogen peroxide-induced DNA damage in human spermatozoa
      was measured with SCGE established by this laboratory. RESULTS: The comet sperm
      cells in human spermatozoa ranged from 2% to 38%. There was a significant
      variance on the percentage of comet cells between different subjects. Hydrogen
      peroxide increased the percentage of comet sperm in a dose- and time-dependent
      manner. CONCLUSION: SCGE may be used to detect DNA strand breakage in human
      spermatozoa. Hydrogen peroxide-induced DNA damage in human sperm cells was
      detected successfully using SCGE protocol established by this laboratory.

PMID- 10932017
TI  - [Polymorphism of human alleles associated with genetic resistance against HIV-1
      infection and its implications].
AB  - To investigate the genetic susceptibility of different ethnic populations to
      human immunodeficiency virus-1(HIV-1) infection by comparing the characteristics
      of gene mutation frequency and polymorphism of CCR5, CCR2 and SDF-1 alleles among
      different nationalities in the world. The recently reported data on AIDS
      progression in patients, and on gene mutation and polymorphism of CCR5, CCR2b and
      SDF-1 genes were collected. The data also included the HIV-1-associated genes
      polymorphisms of the Chinese individuals detected by the present authors. There
      was a significant link between the gene mutation, polymorphism of HIV-1
      associated genes, genetic susceptibilities and the AIDS progression in patients,
      although the differences of HIV-1-associated gene mutation, polymorphisms existed
      among different ethnic populations in the world. The Chinese individuals are more
      likely to be infected by the M-tropic HIV-1 strain than the American Caucasian.
      The Chinese individuals have very low gene mutation of CCR5Delta32, which would
      be helpful for the prevention and gene therapy against the HIV-1 infection.

PMID- 10932019
TI  - Publication and related biases.

PMID- 10932018
TI  - [Advances in the researches of DNA vaccines against tumors].
AB  - The injection of naked plasmid DNA directly into the muscle cells of hosts has
      been shown to induce potent immune responses, as well as to express large amounts
      of gene product; this has provided a new way of treatment for tumor. The past ten
      years have witnessed tremendous growth in the field of gene therapy for cancer
      using intramuscular injection of plasmid DNA. Many studies have suggested that
      the immunostimulatory DNA sequences(ISS) in vector backbone of plasmid DNA,
      delivering adjuvant and mitogenic activity, are necessary for effective
      intradermal gene immunization. It has been postulated that muscle cells serve as
      a reservoir of expressed antigen with subsequent transfer to bone marrow-derived
      APCs. Thus, immunization with plasmid DNA can trigger strong and persistent cell
      mediated and humoral immune responses to the antigen encoded by the plasmid.
      Increasing evidence demonstrates that DNA immunization can prevent or inhibit
      tumor development. In this review, the present authors presented a discussion on
      the characteristics of immune response to DNA vaccines and a summary of the
      effects of immune response against tumors.

PMID- 10932022
TI  - The effectiveness and cost-effectiveness of prophylactic removal of wisdom teeth.
AB  - BACKGROUND: Removal of wisdom teeth is one of the most common surgical procedures
      performed in the UK. Little controversy surrounds the removal of impacted third
      molars when they are associated with pathological changes such as infection, non
      restorable carious lesions, cysts, tumours, and destruction of adjacent teeth and
      bone. However, the justification for prophylactic removal of impacted third
      molars is less certain and has been debated for many years. OBJECTIVES: To
      provide a summary of existing evidence on prophylactic removal of impacted wisdom
      teeth, in terms of the incidence of surgical complications associated with
      prophylactic removal, and the morbidity associated with retention. METHODS: A
      systematic review of the research literature was undertaken. METHODS - DATA
      SOURCES: An existing review formed the basis of this report, and additional
      literature searches were undertaken, including searches of electronic databases
      (MEDLINE, 1984-99; EMBASE, 1984-99; Science Citation Index, Cochrane Controlled
      Trials Register, National Research Register; Database of Abstracts of Reviews of
      Effectiveness), paper sources (including Clinical Evidence), and web-based
      resources. Relevant organisations and professional bodies were contacted for
      further information. METHODS - STUDY SELECTION: Studies were selected for
      inclusion if they met the following criteria: (1) design - randomised controlled
      trials (RCTs), literature reviews, or decision analyses; (2) participants -
      people with unerupted or impacted third molars, or those undergoing surgical
      removal of third molars either as prophylaxis or due to associated pathological
      changes; (3) reported outcomes - either the pathological changes associated with
      retention of third molars, or post-operative complications following extraction.
      There were no language restrictions on study selection. METHODS - DATA EXTRACTION
      AND SYNTHESIS: Data from included studies were extracted into structured tables
      and individual study validity was assessed against methodological checklists.
      Data were summarised descriptively. Decisions relating to study selection, data
      extraction and validity assessment were made by two independent reviewers, and
      disagreements were resolved by discussion. For non-English papers, translators
      were recruited to assist with study selection and data extraction. RESULTS: Forty
      studies were included in the review: two RCTs, 34 literature reviews, and four
      decision analysis studies. One RCT in the UK focused on the effects of retained
      third molars on incisor crowding (predominantly a cosmetic problem) in patients
      who had previously undergone orthodontic treatment. The results of this trial
      suggested that the removal of third molars to prevent late incisor crowding
      cannot be justified. Another on-going RCT in Denmark compares the effects and
      costs of prophylactic removal of third molars with removal according to
      morbidity. So far, this trial has recruited 200 participants, and preliminary
      results indicate that watchful waiting may be a promising strategy. However, more
      data and longer follow-up of patients are needed to conclude which treatment
      strategy is the most cost-effective. It is also known that a trial is on-going in
      the USA but no results are available so far. The methodological quality of the
      literature reviews was generally poor, and none of the reviews was systematic.
      Conclusions from nine reviews on anterior crowding suggested that there was only
      a weak association between retention of third molars and crowding. Six out of 21
      reviews with a more general scope also concluded that the prophylactic removal of
      third molars was unjustified. Twelve general reviews did not conclude with a
      clear message about the management of third molars. Three reviews suggested that
      prophylactic removal of third molars is appropriate, but these reviews were of
      poorer methodological quality than the majority of other reviews. Three out of
      four papers focusing on surgical management expressed

PMID- 10932023
TI  - Liquid-based cytology in cervical screening: a rapid and systematic review.

PMID- 10932027
TI  - Beyond the year 2000 in CHD research: current understanding of the cellular
      mechanism of atherosclerosis.

PMID- 10932028
TI  - Insights into oxidative stress and atherosclerosis.
AB  - Compelling evidence points to oxidative stress as an important trigger in the
      complex chain of events leading to atherosclerosis. Randomized clinical trials
      have not provided definitive evidence of the beneficial effect of antioxidant
      vitamins. Problems associated with the use of vitamins include their potential
      pro-oxidant effects and the decreased absorption of natural gamma-tocopherol
      caused by alpha-tocopherol supplements. Probucol and amlodipine are more powerful
      lipophilic antioxidants than vitamin E. They also do not appear to have
      significant pro-oxidant properties. Probucol has been shown to prevent coronary
      restenosis after balloon angioplasty in clinical trials. Its high density
      lipoprotein-lowering effect, however, prevents it from being protective against
      progression of coronary atherosclerosis. Slowing or reversing the atherosclerotic
      process with an antioxidant likely requires the use of a powerful lipophilic
      antioxidant that has neutral or positive effects on serum lipids when given alone
      or in combination with a lipid-lowering agent.

PMID- 10932029
TI  - Overview of the prospective randomized evaluation of the vascular effects of
      Norvasc (amlodipine) trial: PREVENT.
AB  - The Prospective Randomized Evaluation of the Vascular Effects of Norvase
      (amlodipine) Trial (PREVENT) was designed specifically to assess if amlodipine
      can be shown to inhibit angiographic progression of lesions 30% or less diameter
      stenosis. A carotid ultrasound substudy was also undertaken. The
      antiatherosclerotic effects were discordant in that minor coronary lesions were
      not affected, whereas carotid intima-media thickness showed significantly less
      progression in the amlodipine-treated patients. Moreover, significant cardiac
      events, particularly admissions to hospital for unstable angina and intervention,
      were significantly reduced in the amlodipine-treated patients. This brief report
      provides an overview and assessment of the implications of these findings.

PMID- 10932030
TI  - Results and clinical implications of the CAPARES trial.
AB  - The Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES) is a multicentre,
      double-blind, placebo controlled restenosis trial investigating the effect of
      amlodipine on angiographic and clinical endpoints in patients undergoing routine
      percutaneous transluminal coronary angioplasty (PTCA) for stable angina pectoris.
      A total of 635 patients were randomized to amlodipine or placebo two weeks before
      PTCA and were followed for four months after PTCA. There were 451 nonstented
      patients who completed the study with angiographic follow-up. Quantitative
      coronary angiography revealed that the loss in minimal luminal diameter from
      immediately after PTCA to the four-month follow-up was unaffected by amlodipine
      treatment. However, the incidence of repeat PTCA and composite clinical events
      were significantly lower in patients treated with amlodipine.

PMID- 10932031
TI  - The future of intravascular ultrasound in the detection and management of
      coronary artery disease.
AB  - Stenosis severity may be underestimated by angiography because the reference
      segment used to quantify the lesion is itself narrowed by atherosclerotic plaque.
      Even assessment of the absolute change in lumen diameter on arteriography cannot
      consistently reflect changes in plaque burden because of the variable presence of
      vascular remodelling. Intravascular ultrasound (IVUS) differs radically from
      angiography by providing cross-sectional images of both the coronary arterial
      lumen and the wall with high resolution. The diffuse nature of coronary artery
      disease is readily seen and the majority of angiographically normal reference
      segments are involved in the atherosclerotic process on IVUS imaging. The precise
      assessment of plaque burden by IVUS makes it the ideal tool for a clinical trial
      of progression and regression of atherosclerosis.

PMID- 10932032
TI  - Evidence that a decrease in liver glycogen content stimulates FFA mobilization
      during exercise.
AB  - This study evaluated a liver glycogen content decrease before exercise on the
      metabolic responses during exercise. Rats injected with glucagon (20 microg x kg(
      1)) were compared to rats with a 50% food restriction (1/2-fast) and normally fed
      rats. All were studied at rest and during exercise (26 m/min, 0% grade). Resting
      liver glycogen concentrations were twice as high (P<.01) in normally fed rats,
      with no significant differences between 1/2-fast and glucagon-injected rats.
      During exercise, liver glycogen content was significantly reduced in normally fed
      rats. After exercise, plasma insulin levels were decreased (P<.01) in all groups,
      and beta-hydroxybutyrate concentrations were similar in normally fed and glucagon
      injected rats and significantly (P<.01) lower in 1/2-fast rats. Exercise caused a
      significant increase in FFA concentrations in all groups (P<.01). No significant
      differences in FFA concentrations were found between 1/2-fast and glucagon
      injected groups (P>0.05).

PMID- 10932033
TI  - The effect of endurance training on phosphoinositide metabolism of extensor
      digitorum longus in rat.
AB  - We tested the hypothesis that endurance training results in changes in inositol
      triphosphate (InsP3) production from membrane phosphoinositides in trained
      muscles during contractile activity, which might have implications for fatigue
      involving calcium-release mechanisms. The extensor digitorum longus (EDL) muscles
      of endurance-trained rats were measured for membrane phosphoinositides,
      fatigability, and the production of inositol phosphates resulting from a 10-s
      tetanic contraction in vitro. In the latter, training resulted in a 22% increase
      in the production of inositol phosphates, in spite of lower phosphoinositides per
      muscle. In a separate group of animals, pretreatment of EDL in vitro for 15 min
      with 20 mM lithium resulted in a gradual decrease in tetanic forces at 100 Hz and
      increased fatigability. These results show for the first time that this metabolic
      system adapts to increased use and may contribute to the associated increased
      fatigue resistance, through its modulation of calcium release by sarcoplasmic
      reticulum.

PMID- 10932034
TI  - The effects of acute passive stretch on muscle protein synthesis in humans.
AB  - We examined the effect of an isolated bout of maximal tolerated passive stretch
      on fractional muscle protein synthetic rate in human soleus muscle. Eight healthy
      males performed two separate trials with the same leg: one session of passive
      stretch and one of intermittent active isometric contraction at a force
      equivalent to that which occurred during the passive stretch trial. This force
      was approximately 40% of maximum voluntary contraction force and produced
      volitional fatigue in approximately 27 min. Intermittent passive stretch, for the
      same duration, elicited a 6.1 degrees increase in joint angle (P<.0005) with
      silent electromyography. Fractional protein synthetic rate from experimental and
      control soleus in each trial was assessed from biopsy samples over the period 10
      22 hr postexercise by the incorporation rate of L-[1-13C] leucine into muscle.
      Protein synthesis was elevated in the soleus of the exercised leg following the
      active contraction trial by 49% (P<.05) but not following the passive stretch
      trial. Results indicate that a single bout of maximal passive stretch does not
      significantly elevate fractional muscle protein synthetic rate in humans and thus
      suggests that muscle stretch per se is not the stimulus for the muscle
      hypertrophy that occurs with resistance training.

PMID- 10932035
TI  - Short-term training: when do repeated bouts become training? Introduction to the
      symposium.

PMID- 10932036
TI  - Short-term training: when do repeated bouts of resistance exercise become
      training?
AB  - Chronic resistance training induces increases in muscle fibre cross-sectional
      area (CSA), otherwise known as hypertrophy. This is due to an increased volume
      percentage of myofibrillarproteins within a given fibre. The exact time-course
      for muscle fibre hypertrophy is not well-documented but appears to require at
      least 6-7 weeks of regular resistive training at reasonably high intensity before
      increases in fibre CSA are deemed significant. Proposed training-induced changes
      in neural drive are hypothesized to increase strength due to increased synchrony
      of motor unit firing, reducedant agonist muscle activity, and/or a reduction in
      any bilateral strength deficit. Nonetheless, increases in muscle protein
      synthesis were observed following an isolated bout of resistance exercise. In
      addition, muscle balance was positive, following resistance exercise when amino
      acids were infused/ingested. This showed that protein accretion occurred during
      the postexercise period. The implications of this hypothesis for training-induced
      increases in strength are discussed.

PMID- 10932037
TI  - Effects of short-term training on physiologic properties of human motor units.
AB  - The human neuromuscular system possesses a remarkable ability to adapt to any
      change in the demands placed upon it. Adaptation to training or disuse is
      reflected in the activation patterns and physiologic properties of the motor unit
      (MU) pool in a given muscle group. This review summarizes the studies that have
      examined such adaptation at the level of the single MU. Disuse, as revealed by
      electrophysiologic studies, results in impaired MU recruitment and smaller twitch
      tensions in low and high threshold MUs. Alternatively, shortterm training
      improves MU recruitment and generally results in larger MU twitch tensions. A
      method has been developed to physiologically characterize and longitudinally
      follow single thenar MUs. Studies utilizing these methods have demonstrated that
      MUs differing in their baseline physiologic characteristics respond very
      differently to identical short-term training programs. These observations at the
      single MU level provide insight into training adaptations in whole muscles and
      muscle groups.

PMID- 10932038
TI  - Adaptations in the muscle cell to training: role of the Na+-K+-Atpase.
AB  - The plasticity of skeletal muscle is evident following the onset of regular
      contractile activity where extensive adaptations can be observed at all levels of
      organization. Among the properties subject to altered regulation is the Na+-K+
      ATPase, an integral membrane protein distributed throughout the sarcolemma and t
      tubule, which functions to maintain high Na+ and K+ transmembrane gradients. This
      protein is uniquely positioned to control muscle excitation and contraction
      processes, metabolic flux rates, and contractility. Pronounced and rapid
      upregulation in the Na+-K+-ATPase content can be observed within the first days
      of exercise and well before the other major ATPase proteins involved in Ca2+ and
      actomyosin cycling. Moreover, the Na+-K+-ATPase is subject to complex messenger
      regulation, involved both in the accommodation and the adaptive responses to
      contractile activity. This emphasizes that adaptive responses can be mediated
      soon after the onset of training and may have profound affects on muscle
      contractility and other cellular adaptations.

PMID- 10932039
TI  - [Physiopathology of iodine: current interest of its measurement in biological
      fluids].
AB  - Iodine plays a central role in thyroid physiology, being both a major constituent
      of thyroid hormones and a regulator of thyroid gland functions. Iodine intakes
      considerably vary according to subjects. Inappropriate iodine intakes are
      worrying in term of public health regarding iodine deficiency (western world
      currently is not exempt) and regarding the frequency of iatrogen iodine
      overloads. Iodine disorders induce a biological and/or clinical expression of
      thyroid dysfunction, and in some cases can disclose pre-existent thyroid
      abnormalities. Determination of serum and urine iodine levels is an useful marker
      in the biological investigation of the thyroid function, can contribute to
      undertake an appropriate therapeutics and follow its efficacy.

PMID- 10932040
TI  - [Myelodysplastic syndromes].
AB  - Myelodysplastic syndromes (MDS) are clonal disorders of pluripotent hematopoietic
      stem cells. MDS occur predominantly over the age of 60 years. The diagnosis of
      MDS is based on the examination of both blood films and bone marrow aspirate.
      Diseases such as vitamin B12 and/or folate deficiency, or cytotoxic therapy
      leading to a marrow dysplasia should be ruled out. Five subtypes are described in
      the FAB classification : refractory anaemia or refractory cytopenia, refractory
      sideroblastic anaemia, refractory anaemia with excess of blasts, refractory
      anaemia with excess of blasts in transformation, chronic myelomonocytic
      leukaemia. This FAB classification is based on a small number of parameters:
      percentage of blood and marrow blasts, percentage of ringed sideroblasts and
      blood monocytes. The anaemia is typically normo- or macrocytic, non regenerative,
      and in half cases is associated with neutropenia and/or thrombocytopenia. During
      blood film examination, cell abnormalities have to be notified, i.e.
      anisocytosis, poikilocytosis of red cells, morphological abnormalities of
      neutrophils including hypogranulation, hypolobulation, abnormal large platelets.
      The prognostic and the treatment of MDS depend on the subtype of the FAB
      classification, the patient's age, the percentage of marrow blasts, the
      importance of cytopenia, the presence or not of cytogenetic abnormalities and the
      existence or not of HLA-identical donor.

PMID- 10932041
TI  - [Pseudoleucopenia due to in vitro leukocyte agglutination polynuclear
      neutrophils: experience of a laboratory, review of the literature and future
      management].
AB  - Leukoagglutination is a rare EDTA-dependent phenomenon resulting in a spurious
      minoration of the leukocyte count performed using automated analyzers. We
      described seven cases. The leukocyte agglutination was detected by unstable WBC
      count, abnormal WBC histograms and presence of clusters of polymorphonuclears on
      the smear. PMN aggregates of 3 to 10 cells or bigger were observed. Discrepancies
      between the erroneous automated WBC count and the real count were moderate in
      most cases. Leukoagglutination was related to lymphoproliferative disorders,
      infections, alcoholic liver diseases, auto-immune diseases. Inflammatory context
      seemed to be requested. For few patients, the artefact occurred regardless of the
      type of anticoagulants (lithium heparin, buffered sodium citrate) and warming at
      37 C did not always increase the WBC. Dilution in Unopette chambers was required.
      We confirmed that leukoagglutination of PMN was an in vitro artefact EDTA and/or
      temperature mediated.

PMID- 10932042
TI  - [Hemoglobin A1C determination and hemoglobinopathies: problems and strategies].
AB  - The semiological value of hemoglobin A1c (HbA1c) as a retrospective and
      cumulative marker of glycemic balance in diabetic patients is greatly weakened in
      case of hemoglobinopathy. The presence of an abnormal hemoglobin raises
      methodological problems due to the interferences generated in most assay methods,
      but also alters the normal process of HbA glycation to HbA1c, and often induces a
      certain level of hemolysis, very variable and impossible to quantify. This paper
      reviews methodological and semiological problems related to the presence of
      abnormal hemoglobin species, and proposes a standardized strategy in case of
      hemoglobinopathies.

PMID- 10932043
TI  - [Standards and recommendations for hospital environmental hygiene].
AB  - The hospital laboratory has important responsibilities in the survey, control and
      prevention of nosocomial infections. Contamination of environment (surfaces, air,
      liquids) has been implicated in nosocomial infections. It is essential to develop
      a monitoring system for biocontamination control in the controlled environment
      areas. Classification of zones at risk (low, medium, high and very high risk)
      should be performed according to relevant guidelines or regulations where these
      exist. According to the classification of the zone at risk appropriate levels of
      biocontamination will be assigned. Standards for acceptable levels of
      microbiologic contamination will be suggested because no uniform agreement have
      been achieved because of the lack of correlation between these levels and
      occurrence of clinical infection.

PMID- 10932044
TI  - [The role of integrons in dissemination of antibiotic resistance].
AB  - Bacteria can transfer genetic information to get protection against most
      antibiotics. The acquisition of resistance genes involves genetic mobile elements
      such as plasmids and transposons. Another genetic structures, named integrons,
      have been described and contain one or more gene cassettes located at a specific
      site. Integrons contain an intI gene encoding a site-specific recombinase
      belonging to the integrase family and a recombination site attI. A gene cassette
      includes an open reading frame and, at the 3'-end, a recombination site attC.
      Integration or excision of cassettes occurs by a site-specific recombination
      mechanism catalyzed by the integrase. However, insertion can rarely occur, at non
      specific sites leading to a stable situation for the cassette. Cassettes are
      transcribed from a common promoter located in the 5'-conserved segment and
      expression of distal genes is reduced by the presence of upstream cassettes. Most
      gene cassettes encode antibiotic resistant determinants but antiseptic resistant
      genes have also been described. Integrons seem to have a major role in the spread
      of multidrug resistance in Gram-negative bacteria but integrons in Gram-positive
      bacteria have been recently described. Moreover, the finding of super-integrons
      with gene cassettes coding for other determinants (biochemical functions,
      virulence factors) in different Gram negative bacteria suggests that integrons
      are probably implied in bacterial genome evolution.

PMID- 10932045
TI  - [Two-center evaluation of eight kits for antithyroid peroxidase autoantibodies
      determinations].
AB  - We compared eight antithyroid peroxidase antibody assay kits in two centres, by
      use of panel sera from 269 patients: controls (n = 100), patients with autoimmune
      thyroid diseases (n = 77 Graves' disease, Hashimoto's thyroiditis), with non
      autoimmune thyroid diseases (n = 69 nodular goiter, differentiated thyroid
      carcinoma), and with autoimmune disease without thyroid pathology (n = 23
      diabetic subjects, rheumatoid polyarthritis). On the controls sera we observed
      different distributions of values. The cut-off values of each kit was, in most
      cases, similar to the value noted in the manufacturer's instructions. In the
      clinical study, we observed few differences. The majority of assays demonstrated
      high diagnostic performance. Some false positive results and the non assessment
      of some sera by competitive immunoassay were observed.

PMID- 10932046
TI  - [Molecular analysis and prenatal diagnosis of beta-thalassemia: about our
      experience in central Tunisia].
AB  - Beta-thalassemia, by its high frequency and its heterogeneity, constitutes a real
      problem of health in Tunisia. Prenatal diagnosis by DNA analysis represents the
      only reality for couples at risk. The denaturant gradient (urea and formamide) on
      polyacrylamide gel electrophoresis has been performed in our laboratory, using
      psoralen as chemical clamps. This method is simple, reliable, safe, rapid,
      without radioactivity and has a reasonable cost (chemical clamps). Even if it
      needs an informatic modelization in other laboratories, this method seems to be
      adapted to our economic and work conditions and to the molecular heterogeneity of
      the Tunisian beta-thalassemia. We present the results of an epidemiological
      molecular study on 75 patients with beta-thalassemia and the results of ten
      prenatal diagnosis. The molecular lesions codon 39 (C-T) and IVS1 nt2 (T-G) are
      the most frequent in our study. This technical approach provides genetic
      counselling for at risk families by offering prenatal diagnosis (reducing as
      possible the cost and the delay of the result) after prealable family study and
      identification of the mutation(s).

PMID- 10932047
TI  - [Standardization and automation of HLA B27 typing by flow cytometry: validation
      and comparison with microlymphocytotoxicity].
AB  - One of the strongest known association between human leukocyte antigen (HLA)
      phenotype and disease is that of ankylosing spondylitis and HLA-B27. Thus, the
      determination of HLA-B27 status is an useful tool in the diagnosis of ankylosing
      spondylitis. To date, the 2 reference methods for HLA typing
      (microlymphocytotoxicity and molecular biology techniques), are costly in terms
      of both technician time and materials, and require a great deal of experience. In
      total, these techniques are not well-suited for routine application in clinical
      immunology laboratories. Use of flow cytometry has recently been applied for HLA
      B27 typing. Nevertheless, it requires an extensive validation protocol. We
      developed a flow cytometry technique as standardized as possible (whole blood,
      automated lysing system, automated photomultiplier voltage calibration,
      definition of thresholds stable with time) and validated our results by
      comparison with microlymphocytotoxicity. In total, 326 samples were analyzed. We
      found 99% of concordant results between the 2 techniques, and neither false
      positive results nor false negative results with flow cytometry could be
      observed. These results illustrate the reliability of the protocol. It should be
      remembered that reference technique remains necessary to confirm the few results
      (< 1%) found in "grey zone" by flow cytometry. Standardization of flow cytometry
      techniques, as described in this work for HLA B27, seems to be a reasonable goal
      for the next decade in clinical immunology laboratories.

PMID- 10932049
TI  - [Pre-analytical precautions and appropriate materials for blood gas analysis].

PMID- 10932048
TI  - [Results of hemograms of a series of top-level cyclists: an example of a factor
      of biological variability].
AB  - We report data about 50 caucasian top-level cyclists (45 males, 5 women, aged
      between 16 and 36 years, mean 25 +/- 4.5). Recruitment was by controlling top
      level athletes in order to follow their blood cell counts to detect variation in
      haemoglobin concentration and hematocrit level (prevention of erythropoietin
      abuse). All samples were drawn in the morning, when the cyclists were at rest,
      according to a standardized protocol. Erythroblastic serie was abnormal in
      several cases (4 anaemias, 3 macrocytosis, 6 low haematocrit level, 10 mean cell
      haemoglobin higher than 32 pg, low reticulocyte count). White blood cells showed
      a trend toward low counts for neutrophils and lymphocytes. Two cyclists had
      platelets counts below 150.109/l. Our data indicated that top-level cyclism had
      some effects on the blood cell counts, which is likely to indicate an effect of
      intense aerobic training on physiological status.

PMID- 10932050
TI  - [Role of blood gases and oxygenation indices pulmonary function testing].

PMID- 10932051
TI  - [Monitoring of blood lactate levels in critical care].

PMID- 10932052
TI  - [From quality control to quality insurance in critical care laboratory].

PMID- 10932053
TI  - [A case of coeliac disease].

PMID- 10932054
TI  - [Comparison of the modified Jaffe method and an enzymatic method for the
      measurement of serum creatinine: practical consequences of a method change in the
      milieu of laboratory of oncologic clinical biology].

PMID- 10932055
TI  - [Lymphocytic meningitis associated with post-diarrhea reactive polyarthritis].

PMID- 10932056
TI  - [Reactive thrombocytosis at risk for thrombosis].

PMID- 10932057
TI  - [Internet sources of information: example of a search on Down syndrome (trisomy
      21)].

PMID- 10932058
TI  - [Measurement of urinary proteins with spectro-reflectometric method with Upro
      Vitros plates with pyrocatechol violet: absence of interference of placement
      replacement therapy].

PMID- 10932059
TI  - [Choice of a technique for the serodiagnosis of a first infection with Epstein
      Barr virus].

PMID- 10932060
TI  - Sites internet
AB  - http://biotribune.com/ Biotribune.com ou la biologie medicale sur internet. Ce
      site est concu comme un portail sur la biologie clinique. Accueil d'internautes
      sur une page comportant, entre autres, les rubriques : actualite, evenements,
      revue des connaissances, rubrique juridique et petites annonces. Biotribune
      propose regulierement des dossiers rediges par des specialistes comportant une
      mise a jour des connaissances orientee sur l'interet diagnostique des tests de
      biologie clinique. Le site propose egalement une revue de presse scientifique
      avec des resumes courts d'articles parus dans les grands journaux internationaux
      tels que The Lancet, New England Journal of Medicine, Science, etc. Vous pouvez
      aussi y tester vos connaissances grace a des cas cliniques et des QCM. Ce site
      propose egalement des petites annonces pratiques pour les laboratoires de ville
      (remplacement, materiel d'occasion, etc.). Les problemes touchant l'assurance
      qualite, les RMO et la nomenclature font egalement l'objet d'information et de
      commentaires. Enfin, vous pourrez vous inscrire a l'un des forums proposes :
      discussion biomedicale ou opinion et reaction sur les sujets touchant au
      professionnel de la biologie medicale. En conclusion, un site complet et agreable
      que l'on souhaite voir s'enrichir et se renouveler regulierement.
      http://www.arcol.asso.fr Site du Comite francais de coordination de recherche sur
      l'atherosclerose et le cholesterol (Arcol). Ce site s'adresse a la fois aux
      cliniciens, aux biologistes et aux non-specialistes interesses par la pathologie
      cardio-vasculaire et ses traitements. On y trouve des rubriques tres didactiques
      sur la physiopathologie et les facteurs de risque de l'atherosclerose, la prise
      en charge nutritionnelle et medicamenteuse des patients. On peut tester ses
      connaissances a l'aide des nombreux cas cliniques richement commentes. Ce site
      regulierement mis a jour contient egalement les recommandations nationales et
      internationales sur la prise en charge du patient hyperlipidemique. On y trouve,
      bien sur, toutes les rubriques telles que : agenda des congres, lien avec les
      autres sites web, bibliographie, etc. Un index par mots cles permet une recherche
      efficace. Un site indispensable a consulter pour tous ceux qui s'interessent aux
      lipoproteines et a l'atherosclerose. n R. Couderc

PMID- 10932062
TI  - The role of viral infections in the natural history of asthma.
AB  - Viral infections have been related to the inception of recurrent wheezing
      illnesses and asthma in infants and are probably the most frequent cause of
      exacerbations of established disease in older children and adults. The well
      recognized clinical effects of viral infections are mainly caused by virus
      induced immune responses. Clinical studies of natural and experimentally induced
      viral infections have led to the identification of mechanisms of inflammation
      that could be involved in producing airway obstruction and lower airway symptoms.
      In addition, host factors that are associated with more vigorous viral
      replication or severe clinical illness are beginning to be identified. Advances
      in molecular virology and our understanding of immune responses to viral
      infections may lead to the development of new strategies for the prevention and
      treatment of virus-induced respiratory disorders.

PMID- 10932063
TI  - Chronic sinusitis.
AB  - Sinusitis is a very common chronic illness with a substantial health care impact.
      This review focuses on factors contributing to sinusitis pathogenesis and
      chronicity, including anatomic factors, disturbances in mucociliary clearance,
      microbial pathogens, and inflammatory factors. A distinction is made between
      "infectious" and "noninfectious" types of inflammation in chronic sinusitis. The
      inflammatory characteristics of noninfectious inflammation are reviewed primarily
      in the context of chronic hyperplastic sinusitis with nasal polyposis. Key
      features of this type of inflammation include the presence of chronic
      inflammatory cells, large numbers of eosinophils, and IL-5-producing T
      lymphocytes. Allergic fungal sinusitis is discussed as a special type of chronic
      sinusitis. Published studies on the outcomes of medical management are reviewed.
      Finally, algorithms for medical management of chronic sinusitis and allergic
      fungal sinusitis are presented.

PMID- 10932064
TI  - Structural biology of allergens.
AB  - One of the major challenges of molecular allergy is to predict the allergenic
      potential of a protein, particularly in novel foods. Two aspects have to be
      distinguished: immunogenicity and cross-reactivity. Immunogenicity reflects the
      potential of a protein to induce IgE antibodies, whereas cross-reactivity is the
      reactivity of (usually preexisting) IgE antibodies with the target protein. In
      addition to these two issues, the relation between IgE-binding potential and
      clinical symptoms is of interest. This is influenced by physical properties (eg,
      stability and size) and immunologic properties (affinity and epitope valence).
      Discussions on immunogenicity and cross-reactivity of allergens rely on the
      establishment of structural similarities and differences among allergens and
      between allergens and nonallergens. For comparisons between the 3-dimensional
      protein folds, the representation as 2-dimensional proximity plots provides a
      convenient visual aid. Analysis of approximately 40 allergenic proteins (or parts
      of these proteins), of which the protein folds are either known or can be
      predicted on the basis of homology, indicates that most of these can be
      classified into 4 structural families: (1) antiparallel beta-strands: the
      immunoglobulin-fold family (grass group 2, mite group 2), serine proteases (mite
      group 3, 6, and 9), and soybean-type trypsin inhibitor (Ole e 1, grass group 11);
      (2) antiparallel beta-sheets intimately associated with one or more alpha
      helices: tree group 1, lipocalin, profilin, aspartate protease (cockroach group
      2); (3) (alpha+beta) structures, in which the alpha- and beta-structural elements
      are not intimately associated: mite group 1, lysozyme/lactalbumin, vespid group
      5; and (4) alpha-helical: nonspecific lipid transfer protein, seed 2S protein,
      insect hemoglobin, fish parvalbumin, pollen calmodulin, mellitin from bee venom,
      Fel d 1 chain 1, serum albumin. Allergens with parallel beta-strands (in
      combination with an alpha-helix linking the two strands, a motif commonly found
      in, for example, nucleotide-binding proteins) seem to be underrepresented. The
      conclusion is that allergens have no characteristic structural features other
      than that they need to be able to reach (and stimulate) immune cells and mast
      cells. Within this constraint, any antigen may be allergenic, particularly if it
      avoids activation of T(H)2-suppressive mechanisms (CD8 cells and T(H)1 cells).

PMID- 10932066
TI  - Increasing prevalence of specific IgE to aeroallergens in an adult population:
      two cross-sectional surveys 8 years apart: the Copenhagen Allergy Study.
AB  - BACKGROUND: There is evidence that the prevalence of respiratory allergy has
      increased in children in many countries. However, this evidence is largely based
      on questionnaire data, and little is known about similar trends in adults.
      OBJECTIVE: We investigated whether the prevalence of specific IgE to
      aeroallergens had increased in an adult general population over an 8-year period.
      METHODS: Two cross-sectional surveys were carried out in 1990 and 1998. A mailed
      screening questionnaire on respiratory symptoms sent to random samples of 15- to
      41-year-old subjects living in Copenhagen (Denmark) preceded both surveys. Random
      samples of responders were invited to a health examination, including assessment
      of specific IgE to 6 common aeroallergens. Totals of 312 (74.6% of the invited
      subjects) and 482 (53.4% of the invited subjects) subjects were examined in 1990
      and 1998, respectively. Analyses of serum samples from both surveys were
      performed in 1999. RESULTS: The prevalence of specific IgE to at least one
      allergen increased significantly from 1990 to 1998 (26.5% vs 33.9%; odds ratio
      adjusted for sex, age, and season of examination, 1.63; 95% confidence interval,
      1.15-2.32; P = .006). This increase remained unexplained after adjustment for
      changes in questionnaire variables on lifestyle and home environment. The
      clinical significance of this increase was underlined by a corresponding increase
      in the prevalence of allergic rhinitis symptoms associated with specific IgE
      positivity. CONCLUSION: We found that the prevalence of specific IgE positivity
      to aeroallergens increased in an adult Danish general population from 1990 and
      1998.

PMID- 10932065
TI  - Mechanisms preventing allergen-induced airways hyperreactivity: role of tolerance
      and immune deviation.
AB  - BACKGROUND: Aeroallergens continuously enter the respiratory tract of atopic
      individuals and provoke the development of asthma characterized by airway
      hyperreactivity (AHR) and inflammation. By contrast, nonatopic individuals are
      exposed to the same aeroallergens, but airway inflammation does not develop.
      However, the mechanisms that prevent allergen-induced respiratory diseases in
      nonatopic subjects are poorly characterized. OBJECTIVE: In this study we compared
      the role of allergen-specific T-cell tolerance and immune deviation in conferring
      protection against the development of allergen-induced AHR. METHODS: We exposed
      mice to intranasal ovalbumin (OVA) to induce T-cell tolerance and examined its
      effects on the subsequent development of AHR and inflammation. RESULTS: We
      demonstrated that exposure of mice to intranasal OVA resulted in peripheral
      CD4(+) T-cell unresponsiveness that very efficiently prevented not only the
      development of AHR but also greatly inhibited airway inflammation and OVA
      specific IgE production. The induction of peripheral T-cell tolerance and
      protection against AHR were not dependent on the presence of IFN-gamma or IL-4.
      The development of AHR was also prevented by an OVA-specific T(H)1-biased immune
      response induced by inhalation of OVA in the presence of IL-12. However, the OVA
      specific T(H)1 response was associated with a significant degree of pulmonary
      inflammation. CONCLUSION: These results indicate that both allergen-specific T
      cell tolerance and T(H)1-biased immune deviation prevent the development of AHR,
      but T(H)1 responses are associated with significantly greater inflammation in the
      lung than is associated with T-cell unresponsiveness. Therefore CD4(+) T-cell
      unresponsiveness critically regulates immune responses to aeroallergens and
      protects against the development of allergic disease and asthma.

PMID- 10932067
TI  - Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal
      allergic rhinitis.
AB  - BACKGROUND: Allergic rhinitis is a common condition often requiring treatment.
      OBJECTIVE: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant
      humanized construct of a murine antibody that binds to circulating IgE, could
      control symptoms and reduce intake of concomitant medication in seasonal allergic
      rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule
      predicted to reduce serum free IgE levels below 25 ng/mL. METHODS: We randomly
      assigned 251 adult subjects with a history of SAR and a positive skin test
      response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3
      times during the season, depending on baseline IgE levels. The primary efficacy
      variable was the subject's average daily nasal symptom severity score (sneezing,
      itching, runny, and stuffy nose) from diary data collected over the double-blind
      treatment period. Secondary efficacy variables included the average number of
      rescue antihistamine tablets per day, the proportion of days with any SAR
      medication use, and rhinoconjunctivitis-specific quality of life (QOL). RESULTS:
      Significant between-treatment differences in favor of rhumAb-E25 were observed in
      average daily nasal symptom severity scores, the average number of tablets of
      rescue antihistamines per day, the proportion of days with any SAR medication
      use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb
      E25-treated subjects and were associated with clinical effectiveness. Recombinant
      humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were
      detected. CONCLUSION: Compared with placebo, rhumAb-E25 was safe and effective in
      controlling birch pollen-induced SAR symptoms, with less concomitant medication
      use and improved QOL. This study shows the therapeutic potential of anti-IgE
      antibody in SAR.

PMID- 10932068
TI  - A springtime olympics demands special consideration for allergic athletes.
AB  - BACKGROUND: The Sydney Olympic and Paralympic Games will be held in September
      October 2000, which is early to mid-spring in the southern hemisphere. Pollen
      sensitive athletes may encounter problems with allergic symptoms triggered by
      pollen exposure, thus compromising their ability to attain peak performance.
      OBJECTIVE: We sought to monitor pollen levels at the major Olympic venues to
      provide information for allergic athletes and their team doctors in order to
      adequately prepare them for Olympic competition. METHODS: We performed
      aerobiologic monitoring of the major Olympic venues to provide a profile of the
      most prevalent pollen species appearing during the spring. In the second part of
      this study, we surveyed a population of elite Australian athletes from Olympic
      sports to ascertain the prevalence of allergic rhinoconjunctivitis, to
      investigate the major allergens involved in sensitization, and to conduct a pilot
      study to assess the effect of allergic rhinoconjunctivitis on quality of life.
      RESULTS: The pollen counts obtained at the 3 major sites were high over the
      period of Olympic competition. Tree pollens appeared from July, and grasses
      appeared from early September and peaked in the second week of October, the
      beginning of Paralympic competition. A relatively small number of pollen
      varieties comprise the majority of the total pollen count. Two hundred fourteen
      athletes (61% male; mean age, 21 +/- 16 years) representing 12 Olympic sports
      participated in the study. Fifty-six percent gave a symptom history consistent
      with allergic rhinoconjunctivitis, 41% had symptoms of allergic
      rhinoconjunctivitis and a positive test response to any one allergen, and 29% had
      seasonal allergic rhinoconjunctivitis (a positive history and at least one
      positive skin prick test response to a seasonal allergen). Athletes from aquatic
      sports were more likely to have symptoms than those from other sports. Symptom
      scores were higher and quality of life ratings were poorer in allergic compared
      with nonallergic athletes over the spring period. CONCLUSION: Olympic team
      managers and medical officers need to adequately prepare Olympic athletes for the
      possibility of exposure to high pollen levels in the weeks leading up to this
      most important sporting event. Symptoms of pollen sensitivity, such as
      rhinoconjunctivitis and exacerbation of asthma, could be devastating to athletes
      expecting peak performance. Potential Olympic athletes should be screened for the
      possibility of pollen allergy and have medical programs with permitted medication
      tailored to meet their needs. This may involve preventative therapy with
      medication, such as intranasal corticosteroid sprays or immunotherapy programs,
      if symptoms are particularly severe. The newer nonsedating antihistamines are the
      treatment of choice for acute intermittent symptoms. Appropriate management will
      ensure that the allergic athlete will safely perform to maximum ability with
      permitted medication during the Spring 2000 Olympic Games in Sydney.

PMID- 10932069
TI  - Asthma in United States olympic athletes who participated in the 1998 olympic
      winter games.
AB  - BACKGROUND: About one of every 5 athletes who participated in the 1996 Summer
      Olympic Games in Atlanta had a past history of asthma, had symptoms that
      suggested asthma, or took asthma medications. No previous study has determined
      the prevalence of asthma in all US athletes who participated in an Olympic Winter
      Games. OBJECTIVES: We sought to determine how many US athletes who participated
      in the 1998 Olympic Winter Games had a past history of asthma, had symptoms that
      suggested asthma, or indicated taking a medication used to treat asthma. METHODS:
      We evaluated responses to questions that asked about allergic and respiratory
      diseases in the United States Olympic Committee Medical History Questionnaire
      that was completed by all 196 athletes who represented the United States at the
      1998 Olympic Winter Games in Nagano, Japan. RESULTS: Forty-three (21.9%) of the
      196 athletes had a previous diagnosis of asthma, and 36 (18. 4%) recorded use of
      an asthma medication at some time in the past. Forty-four (22.4%) reported use of
      an asthma medication, a diagnosis of asthma, or both (our basis for the diagnosis
      of asthma). Thirty-four (17.4%) of the athletes were currently taking an asthma
      medication at the time that they completed the questionnaire or indicated that
      they took these medications on a permanent or semipermanent basis and were
      considered to have active asthma. Athletes who participated in Nordic combined,
      cross-country, and short track events had the highest prevalence of having been
      told that they had asthma or had taken an asthma medication in the past (60.7%)
      in contrast with only one (2.8%) of the 36 athletes who participated in bobsled,
      biathlon, luge, and ski jumping. Eighteen (24%) of 75 athletes who participated
      in alpine, long track, figure skating, snow boarding, and curling had a previous
      diagnosis of asthma or recorded use of an asthma medication. CONCLUSIONS: We
      conclude that asthma appeared to have been more common in athletes who
      participated in the 1998 Winter Games than in athletes who participated in either
      the 1996 or 1984 Summer Games. Clearly, asthma rates vary widely among sports.
      This suggests that the environment in which exercise is performed is important in
      leading to a decrease in the amount of exercise required to trigger asthma and
      perhaps in causing injury to the airways.

PMID- 10932070
TI  - Involvement of ion channels in human eosinophil respiratory burst.
AB  - BACKGROUND: Human eosinophils possess a variety of ion channels that play a
      crucial role in the regulation of cellular activity. During eosinophil
      respiratory burst, efflux of H(+) ions through H(+) channels provides an
      efficient mechanism of H(+) extrusion and charge compensation. Interestingly,
      recent studies suggest that other ion channels may also be involved in this
      process. OBJECTIVE: We sought to investigate the role of ion channels in phorbol
      12-myristate 13-acetate-induced superoxide (O(2)(*-)) generation by human
      eosinophils. METHODS: O(2)(*-) production was measured by using the superoxide
      dismutase-inhibitable reduction of cytochrome c. Ion channel expression and
      function were studied by using RT-PCR and the patch clamp technique,
      respectively. RESULTS: O(2)(*-) generation was affected by several ion channel
      blockers, especially 4,4-diisothio-cyanostilbene-2,2'-disulfonic acid. The
      involvement of Cl(-) channels in this process was confirmed by replacement of Cl(
      ) with gluconate or other anions. The halide dependence of O(2)(*-) production
      could be described by the sequence Cl(-)> or =Br(-)>I(-), which is similar to the
      selectivity sequence of several members of the chloride channel (ClC) family. RT
      PCR studies performed with primers for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6, and the
      cystic fibrosis transmembrane conductance regulator showed only the expression of
      ClC-3. The presence of phorbol 12-myristate 13-acetate-sensitive Cl(-) channels
      in human eosinophils with biophysical properties similar to the ClC-3 channel has
      been studied. CONCLUSION: Cl(-) channels play an important role in the regulation
      of O(2)(*-) production by human eosinophils.

PMID- 10932071
TI  - Suppression of human IL-1beta, IL-2, IFN-gamma, and TNF-alpha production by
      cigarette smoke extracts.
AB  - BACKGROUND: Although cigarette smoking is known to have detrimental effects on
      the immune system, the nature of the immunosuppressive agent or agents is poorly
      understood. OBJECTIVE: The purpose of the current study was to evaluate the
      effects of cigarette smoke extracts from high-tar (unfiltered Camel), medium-tar
      (Marlboro), and low-tar (Carlton) cigarettes on the in vitro production of IL
      1beta, IL-2, IFN-gamma, and TNF-alpha. METHODS: The concentrations of
      hydroquinone and catechol in cigarette smoke extracts were determined by using
      HPLC. Human PBMCs were treated with cigarette smoke extracts, hydroquinone, or
      catechol, and stimulated with anti-CD3 and phorbol-12-myristate-13-acetate.
      Cytokine levels in the supernatants were quantified by ELISA. RESULTS:
      Pretreatment of PBMCs with cigarette smoke extracts derived from a single high-
      or low-tar cigarette suppressed the production of IL-1beta, IL-2, IFN-gamma, and
      TNF-alpha by greater than 90% without significant loss of cell viability.
      Nicotine, at a concentration comparable with that found in the highest-tar
      cigarettes (200 microg/mL), suppressed the production of IL-2, IFN-gamma, and TNF
      alpha by only 21% to 38%. Catechol (50 micromol/L) inhibited production of IL-2
      and IL-1beta by 62% to 73% but had little effect on TNF-alpha or IFN-gamma
      production. In contrast, hydroquinone inhibited the production of all 4 cytokines
      with IC(50) values ranging from 3 micromol/L(IL-1beta) to 29 micromol/L (IFN
      gamma). However, HPLC determination of the hydroquinone concentrations in
      cigarette smoke extracts from single Camel (33+/-4 micromol/L), Marlboro (13+/-2
      micromol/L), and Carlton (<1 micromol/L) cigarettes clearly demonstrated that the
      potent inhibitory effects of the low-tar cigarettes could not be accounted for by
      either hydroquinone or catechol. CONCLUSION: These studies indicate that
      cigarette smoke contains potent inhibitors of cytokine production, at least one
      of which is present even in low-tar cigarettes.

PMID- 10932072
TI  - Evidence for expression of eosinophil-associated IL-12 messenger RNA and
      immunoreactivity in bronchial asthma.
AB  - BACKGROUND: Eosinophils are a source of cytokines within the airways of asthmatic
      individuals that may exert an important immunoregulatory influence. OBJECTIVES:
      We examined IL-12 messenger (m)RNA and protein expression in eosinophils from
      peripheral blood and bronchoalveolar lavage (BAL) fluid obtained from subjects
      with atopic asthma (n = 7), patients with chronic bronchitis (n = 5), and
      nonatopic healthy control subjects (n = 7). To further define this IL-12(+)
      population of eosinophils for the expression of other cytokines, we colocalized
      IL-12 and IL-5 within the peripheral blood eosinophils. METHODS: To detect IL-12
      mRNA and protein expression, we used in situ hybridization and
      immunocytochemistry techniques. The double-immunocytochemistry technique was used
      to localize IL-12 protein to BAL eosinophils and to colocalize IL-5 and IL-12 in
      peripheral blood eosinophils. RESULTS: IL-12 mRNA and immunoreactive protein were
      localized to peripheral blood eosinophils. BAL fluid-derived eosinophils from
      asthmatic subjects were also reactive to IL-12. The percentage of peripheral
      blood eosinophils expressing mRNA for IL-12 was significantly lower in asthmatic
      subjects compared with that found in eosinophils obtained from patients with
      chronic bronchitis (P<.001) and control patients (P <.05). Colocalization studies
      demonstrated that the percentages of IL-12(+) eosinophils that are also IL-5(+)
      were 72% in asthmatic subjects and only 11% in control subjects (P<.001).
      CONCLUSION: These results suggest that eosinophils are a potential source of IL
      12. Eosinophil-derived IL-12 may contribute and modulate the local allergic
      inflammatory responses.

PMID- 10932073
TI  - Increased expression of IL-16 immunoreactivity in bronchial mucosa after
      segmental allergen challenge in patients with asthma.
AB  - BACKGROUND: We have previously shown increased expression of the CD4(+) cell
      chemoattractant IL-16 in bronchial mucosa of patients with asthma. We
      investigated the effects of allergen challenge on airway IL-16 expression.
      METHODS: We investigated the expression of IL-16 immunoreactivity in bronchial
      biopsy samples obtained from atopic asthmatic subjects (n = 19) and normal
      subjects (n = 6) 24 hours after segmental allergen challenge. Control biopsy
      samples were obtained either at baseline or after diluent challenge. IL-16
      expression was correlated to numbers of CD4(+) cells, CD25(+) cells, and
      activated eosinophils. IL-16 bioactivity was assessed in bronchoalveolar fluid
      obtained from patients with asthma. RESULTS: IL-16 expression was higher in
      control biopsy specimens obtained from subjects with asthma compared with normal
      subjects (P<.05). In patients with asthma, numbers of IL-16 immunoreactive cells
      were significantly higher in biopsy specimens obtained after allergen challenge
      compared with control biopsy specimens (P<.001). Allergen provocation was
      associated with release of IL-16 in bronchoalveolar fluid in patients with
      asthma. In normal subjects, there was no difference in the number of IL-16
      immunoreactive cells in biopsy specimens obtained after allergen challenge
      compared with biopsy specimens obtained after diluent challenge. Allergen
      challenge was associated with an increase in the numbers of EG2(+) eosinophils in
      patients with asthma but not in normal subjects. IL-16 expression correlated with
      the numbers of CD4(+) cells and CD25(+) cells after allergen challenge in
      asthmatic subjects with a provocative concentration required to decrease the
      FEV(1) by 20% of its baseline value (PC(20)FEV(1)) < 4 mg/mL. IL-16
      immunoreactive cells were identified mainly as T cells and eosinophils in
      asthmatic subjects after allergen challenge. CONCLUSION: Endobronchial allergen
      provocation in atopic asthmatic patients resulted in increased airway expression
      of IL-16 and release of bioactive IL-16 in airways. IL-16 may contribute to the
      immunoregulation of the inflammatory infiltrate in the airways in response to
      antigen.

PMID- 10932074
TI  - Effect of maternal diet during lactation on development of bovine insulin-binding
      antibodies in children at risk for allergy.
AB  - BACKGROUND: The role of exposure to dietary antigens through maternal milk is
      intriguing, because it may result either in immunization or in tolerance.
      Exposure to cow's milk proteins results in antibody formation against bovine
      insulin in infants at risk for type 1 diabetes. OBJECTIVE: To study the
      appearance of IgG antibodies to bovine and human insulin in infants with an
      atopic family history whose mothers followed a cow's milk-free diet during the
      first 3 months of lactation. METHODS: In a prospective cohort study on prevention
      of food allergies, 123 infants were exclusively breast-fed or received
      supplementation with a hydrolyzed casein-based formula (Nutramigen) until the age
      of 6 months. The mothers either avoided cow's milk during the first 3 months of
      lactation (diet group) or had an unrestricted diet (nondiet group). The levels of
      IgG antibodies to bovine and human insulin were determined by enzyme immunoassay
      at 3, 6, 12, and 18 months and at 4 years. In addition, cord blood was obtained
      at birth and a maternal sample at delivery. RESULTS: At 3 months, IgG antibodies
      to bovine insulin were low in both dietary groups (median levels 0.150 and 0. 114
      optical density units in the diet and nondiet groups). After exposure to dietary
      insulin, IgG antibodies to bovine insulin increased in both groups, reaching a
      peak at 12 months in the nondiet group and at 18 months in the diet group. At 18
      months, IgG antibodies to bovine insulin were lower in infants in the nondiet
      group than in infants in the diet group (0.287 vs 0.500, P<.0001). At 4 years,
      the antibodies no longer differed between the groups. CONCLUSION: The exposure to
      cow's milk proteins through breast milk during the first 3 months of life
      resulted in decreased levels of antibodies to dietary bovine insulin at 18 months
      of age, suggesting a role for breast milk antigens in early tolerance induction.

PMID- 10932075
TI  - Topical steroid treatment of allergic rhinitis decreases nasal fluid TH2
      cytokines, eosinophils, eosinophil cationic protein, and IgE but has no
      significant effect on IFN-gamma, IL-1beta, TNF-alpha, or neutrophils.
AB  - BACKGROUND: Topical treatment with glucocorticoids (GCs) is known to decrease
      eosinophils but not neutrophils in patients with allergic rhinitis. OBJECTIVE: We
      sought to examine whether the differential effects of GC treatment on eosinophils
      and neutrophils are mirrored by differential effects on T(H)1/T(H)2 cytokines and
      the neutrophil-associated cytokines IL-1beta and TNF-alpha. METHODS: Differential
      counts of eosinophils and neutrophils in nasal fluids from 60 children with
      seasonal allergic rhinitis treated with a topical GC were examined after staining
      with May-Grunwald-Giemsa stain. Nasal fluid levels of IFN-gamma, IL-4, IL-6, IL
      10, IL-1beta, and TNF-alpha were examined with ELISA, and IgE and eosinophil
      cationic protein (ECP) levels were examined with RIA. RESULTS: After GC
      treatment, there was a statistically significant decrease of the T(H)2 cytokines
      IL-4, IL-6, and IL-10, as well as ECP and IgE. By contrast, there were no
      significant changes of the levels of IFN-gamma, IL-1beta, TNF-alpha, or
      neutrophils. In the GC-treated patients IL-1beta and TNF-alpha levels correlated
      with neutrophils and ECP, and IL-1beta correlated with eosinophils. Furthermore,
      ECP correlated with both eosinophils and neutrophils. Neither IL-1beta nor TNF
      alpha correlated with IgE. Patients with high neutrophil counts after GC
      treatment were found to have significantly higher eosinophil counts and ECP than
      patients with low counts. CONCLUSIONS: The beneficial effects of topical
      treatment with GC in patients with allergic rhinitis could be attributed to
      downregulation of T(H)2 cytokines, with an ensuing decrease of eosinophils, ECP,
      and IgE. It is possible that neutrophils could counteract the beneficial effects
      of GCs by releasing the proinflammatory cytokines IL-1beta and TNF-alpha.

PMID- 10932076
TI  - Chemokine stromal cell-derived factor 1alpha activates basophils by means of
      CXCR4.
AB  - BACKGROUND: The CXC chemokine receptor 4 (CXCR4) is predominantly expressed on
      inactivated naive T lymphocytes, B lymphocytes, dendritic cells, and endothelial
      cells. CXC chemokine stromal cell-derived factor 1alpha (SDF-1alpha) is the only
      known ligand for CXCR4. To date, the CXCR4 expression and function of SDF-1alpha
      in basophils are unknown. OBJECTIVE: The purpose of this study was to investigate
      the expression of CXCR4 and functions of SDF-1alpha in basophils and to
      characterize the role of the CXCR4-SDF-1alpha receptor ligand pair in the
      allergic inflammation. METHODS: Basophil purification, flow cytometry, real-time
      quantitative RT-PCR assay, Northern blotting, intracellular free Ca(2+) change,
      chemotaxis assay, and histamine release assay were used. RESULTS: CXCR4 is
      abundantly expressed on peripheral blood resting basophils (91%). Likewise, CXCR4
      messenger (m)RNA is expressed in resting basophils (3.2 x 10(3) copies per 2 x
      10(2) cells). The existence of CXCR4 mRNA was also confirmed in basophils by
      means of Northern blot analysis. SDF-1alpha induces an increase in intracellular
      free Ca(2+) in basophils. SDF-1alpha activates basophils to chemotaxis
      (chemotactic index = 3.8) and histamine release (36% of total content) through
      CXCR4 on the cells. The chemokines SDF-1alpha, eotaxin, RANTES, monocyte
      chemoattractant protein (MCP) 1, and macrophage inflammatory protein (MIP) 1alpha
      have been demonstrated at different potencies in induction of chemotaxis (eotaxin
      > SDF-1alpha > RANTES congruent with MCP-1 >> MIP-1alpha) and histamine release
      (MCP-1 congruent with SDF-1alpha > eotaxin > RANTES > MIP-1alpha). The optimal
      concentration seen for SDF-1alpha effects (chemotaxis and histamine release) on
      basophils was 100 ng/mL. CONCLUSION: These results indicate that the CXCR4-SDF
      1alpha receptor ligand pair may be important for the recruitment and activation
      of the basophils, which is a characteristic effector cell of the allergic
      inflammation.

PMID- 10932077
TI  - Regulation of chymase production in human mast cell progenitors.
AB  - BACKGROUND: Although mature tryptase-positive mast cells (MCs) and tryptase and
      chymase double-positive MCs are recognized using in situ staining and are
      preferentially distributed in different tissues, recent findings suggest that
      tryptase-positive MCs can give rise to tryptase and chymase double-positive MCs.
      OBJECTIVE: We investigated the regulation of chymase production in developing
      MCs. METHODS: Human cord blood or peripheral blood cells were cultured in the
      presence of stem cell factor and IL-6 with or without IL-4 in methylcellulose or
      liquid medium. Intracellular chymase and tryptase were determined with
      immunocytochemistry, flow cytometry, and ELISA. Chymase messenger RNA expression
      was examined with 3 different methods, such as Northern blotting. RESULTS: Flow
      cytometric analysis always showed a unimodal histogram of chymase-positive, as
      well as tryptase-positive, cells in the presence of various cytokines, even when
      chymase was not detected in some MCs with immunocytochemistry. The chymase
      protein expression increased by culture duration and was enhanced by cytokines,
      such as a high concentration of stem cell factor or IL-4. Chymase messenger RNA
      was expressed higher in immature MCs than mature chymase protein-rich MCs. We
      generated macroscopic MC colonies in methylcellulose by culturing CD34(+) cells
      for 10 weeks and measured cellular chymase, tryptase, and histamine. The
      chymase/histamine ratio widely varied (0.07-1.01) depending on MC colony, even
      under the same culture conditions, including IL-4, whereas the tryptase/histamine
      ratio was relatively constant (1.02-1.89). CONCLUSION: All human MCs in culture
      are capable of producing chymase, and the production is clonally regulated at
      their progenitors by cytokine-independent mechanisms, as well as being totally
      controlled by cytokine-dependent mechanisms accompanied by maturation.

PMID- 10932078
TI  - IL-5 production by bone marrow stromal cells: implications for eosinophilia
      associated with asthma.
AB  - BACKGROUND: Eosinophil infiltration of bronchial tissue is a hallmark of asthma.
      Recruitment of eosinophils into pulmonary tissue is dependent on the presence of
      IL-5. In addition, IL-5 plays a significant role in the differentiation,
      proliferation, and maturation of eosinophil progenitor cells in the bone marrow
      before recruitment into the lung. The contribution of bone marrow eosinophil
      production to eosinophilia associated with asthma is poorly understood.
      OBJECTIVE: The aims of this study were to determine whether bone marrow stromal
      cells produce IL-5 and to determine whether IL-5 production by stromal cells is
      upregulated by IL-1, an inflammatory cytokine associated with asthma. METHODS: IL
      5 messenger (m)RNA from bone marrow stromal cells was amplified by RT-PCR and
      sequenced. Stromal cells were lysed, and IL-5 protein production was measured by
      ELISA. Upregulation of stromal cell IL-5 transcription, translation, and
      functional effect on eosinophil differentiation was evaluated after stimulation
      with recombinant IL-1alpha and IL-1beta and compared with untreated cells.
      RESULTS: Bone marrow stromal cells transcribe and translate IL-5. The nucleotide
      sequence of IL-5 mRNA from stromal cells was identical to that previously
      reported for murine T cells. IL-5 mRNA abundance in stromal cells increased with
      increasing cell confluence in culture. IL-5 mRNA and protein levels were
      upregulated by exposure of stromal cells to the inflammatory cytokines IL-1alpha
      and IL-1beta. Exposure of stromal cells to IL-1 resulted in increased eosinophil
      differentiation in coculture experiments with nonadherent bone marrow cells.
      CONCLUSION: The production of IL-5 mRNA and protein by bone marrow stromal cells
      is a novel finding that has implications for both normal eosinophilopoiesis and
      development of the accelerated eosinophil production associated with asthma.

PMID- 10932079
TI  - Negative regulation of FcepsilonRI signaling by FcgammaRII costimulation in human
      blood basophils.
AB  - BACKGROUND: Signaling through the antigen receptors of human B and T cells and
      the high-affinity IgE receptor FcepsilonRI of rodent mast cells is decreased by
      cross-linking these receptors to the low-affinity IgG receptor FcgammaRII. The
      inhibition is thought to involve the tyrosine phosphorylation of immunoreceptor
      tyrosine-based inhibitory motifs (ITIMs) in the FcgammaRIIB cytoplasmic tail,
      creating binding sites for SH2-containing protein (Src homology domain containing
      protein tyrosine phosphatase 1 and 2 [SHP-1, SHP-2]) and/or lipid (SH2 domain
      containing polyphosphatidyl-inositol 5-phosphatase) phosphatases that oppose
      activating signals from the costimulated antigen receptors. OBJECTIVE: In human
      basophils and mast cells FcepsilonRI signaling generates mediators and cytokines
      responsible for allergic inflammation. We proposed to determine whether
      FcepsilonRI signaling is inhibited by FcgammaRII costimulation in human basophils
      and to explore the underlying mechanism as an approach to improving the treatment
      of allergic inflammation. METHODS: FcgammaR expression on human basophils was
      examined using flow cytometry and RT-PCR analysis. FcgammaRII/FcepsilonRI
      costimulation was typically accomplished by priming cells with anti-dinitrophenol
      (DNP) IgE and anti-DNP IgG and stimulating with DNP-BSA. Phosphatases were
      identified by Western blotting, and their partitioning between membrane and
      cytosol was determined by cell fractionation. Biotinylated synthetic peptides and
      phosphopeptides corresponding to the FcgammaRIIB ITIM sequence were used for
      adsorption assays. RESULTS: We report that peripheral blood basophils express
      FcgammaRII (in both the ITIM-containing FcgammaRIIB and the immunoreceptor
      tyrosine-based activation motif-containing FcgammaRIIA forms) and that
      costimulating FcgammaRII and FcepsilonRI inhibits basophil FcepsilonRI-mediated
      histamine release, IL-4 production, and Ca(2+) mobilization. The inhibition of
      basophil FcepsilonRI signaling by FcgammaRII/FcepsilonRI costimulation is linked
      to a significant decrease in Syk tyrosine phosphorylation. Human basophils
      express all 3 SH2-containing phosphatases. CONCLUSIONS: Evidence that
      FcgammaRII/FcepsilonRI costimulation induces SHP-1 translocation from the
      cytosolic to membrane fractions of basophils and that biotinylated synthetic
      peptides corresponding to the phosphorylated FcgammaRIIB ITIM sequence
      specifically recruit SHP-1 from basophil lysates particularly implicates this
      protein phosphatase in the negative regulation of FcepsilonRI signaling by
      costimulated FcgammaRII.

PMID- 10932080
TI  - DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in
      mice.
AB  - BACKGROUND: Anaphylactic hypersensitivity is the most serious clinical concern
      facing allergists. However, for the majority of anaphylactic hypersensitivities,
      avoidance is the only therapeutic option presently available. OBJECTIVE: This
      study evaluated the effectiveness of primary gene and protein-immunostimulatory
      DNA vaccination in the prevention of anaphylactic hypersensitivity in a murine
      model. METHODS: Female C3H/HeJ mice were immunized with a plasmid encoding beta
      galactosidase (beta-gal) or beta-gal protein plus an immunostimulatory sequence
      oligodeoxynucleotide. The mice were then T(H2) sensitized to beta-gal by
      coinjection with alum and pertussis and then intravenously challenged with this
      model allergen. RESULTS: Primary gene and protein-immunostimulatory DNA
      vaccination of subsequently T(H2)-sensitized mice reduced the risk of death after
      anaphylactic challenge from 100% to 67% and 58%, respectively (P<.018 vs control
      mice). In addition, gene and protein-immunostimulatory DNA vaccination reduced
      postchallenge plasma histamine levels by greater than 4-fold (P <.05 vs control
      mice). Consistent with previous studies, these DNA-based vaccination strategies
      were further shown to blunt the development of T(H2)-biased immune responses
      after allergen sensitization. Vaccination with protein alone, the experimental
      equivalent of a traditional immunotherapy reagent, provided no protection from
      anaphylaxis nor did it prevent the development of a T(H2)-biased immune profile
      after allergen sensitization. CONCLUSION: The present series of experiments
      demonstrate that both gene vaccination and coimmunization with protein and
      immunostimulatory DNA are effective in attenuating the development of
      anaphylactic hypersensitivity in subsequently T(H2) sensitized mice.

PMID- 10932081
TI  - Antigen-specific and nonspecific determinants of cytokine production during
      topical sensitization of mice to chemical allergens.
AB  - BACKGROUND: Topical exposure to chemical allergens such as trimellitic anhydride
      or 1-chloro-2,4-dinitrochlorobenzene results in the accumulation of dendritic
      cells (DCs) and subsequent rapid up-regulation of CD4 T-cell proliferation and
      cytokine secretion within draining lymph nodes. OBJECTIVE: We investigated the
      contribution of antigen-specific and CD40 ligand (CD40L)-mediated signals to
      chemical allergen-induced CD4 T-cell growth and cytokine production. METHODS: DCs
      enriched from lymph nodes of allergen-challenged animals by metrizamide
      centrifugation were used to stimulate cytokine and proliferative responses by
      magnetic immunobead-sorted CD4 T cells primed in vivo with the same or unrelated
      allergen. Cultures of DCs and T cells were supplemented with antibodies that
      block IL-12 and CD40L activity. RESULTS: Proliferation of CD4 T cells was
      stimulated by DCs primed with the same but not unrelated antigen, whereas IFN
      gamma, IL-12, and IL-10 secretion were provoked equally well by DCs primed with
      either hapten. Blockade of CD40L engagement abrogated production of IFN-gamma
      (80%) and IL-12 (95%) under antigen-nonspecific stimulatory conditions. In
      contrast, IL-10 secretion was enhanced after CD40L blockade under both antigen
      specific and nonspecific conditions. Primary CD4 T cells activated by mitogen
      were also influenced by DCs in the same way. CONCLUSION: These results show that
      during the development of chemical sensitization emerging CD4 T-cell growth and
      cytokine production are regulated by independent mechanisms requiring antigen
      presentation and CD40 signaling, respectively.

PMID- 10932082
TI  - Allergy to iguana.
AB  - BACKGROUND: Furry animals produce allergens that can cause allergic rhinitis and
      asthma. In contrast, scaly animals, such as lizards, are assumed not to be
      allergenic. OBJECTIVE: We sought to evaluate a 32-year-old man who complained of
      allergic rhinitis and asthma symptoms that occurred exclusively in his own home.
      He had dogs and cats at home but denied any increase in symptoms specifically
      associated with these pets. Skin prick testing initially performed to 42 common
      aeroallergens, including cat, dog, and house dust mite, elicited negative
      results. He later reported that the symptoms were worse on exposure to his pet
      iguanas. METHODS: Skin prick tests were subsequently performed to an extract made
      from scales from his pet iguana. Extracts were also prepared from several zoo
      reptiles. Immunoassays for IgE antibody, as well as IgE immunoblots, were
      performed by using these extracts and the patient's serum. RESULTS: The skin
      prick test result with the pet iguana scale extract was positive. The patient's
      serum contained IgE antibody to his own pet iguana and to a zoo iguana.
      CONCLUSION: Our patient's history, skin test results, and in vitro studies
      clearly demonstrate that he is allergic to iguana. Physicians should be aware
      that such allergy to scaly pets may occur and should not restrict history taking
      to questions about furry pets.

PMID- 10932083
TI  - Celery allergy confirmed by double-blind, placebo-controlled food challenge: a
      clinical study in 32 subjects with a history of adverse reactions to celery root.
AB  - BACKGROUND: Celery root is a frequent cause of food allergy in pollen-sensitized
      patients. Because of problems in blinding challenges with fresh vegetables and
      the risk of anaphylactic reactions, no double-blind, placebo-controlled, food
      challenges (DBPCFCs) with celery have been published so far. OBJECTIVE: The aim
      of the study was to confirm the clinical relevance of celery as a food allergen
      by DBPCFCs and to evaluate current diagnostic procedures in patients with true
      allergy. METHODS: DBPCFCs were performed in 32 patients with a history of an
      allergic reaction to celery. The patients underwent skin prick tests (SPTs) with
      celery extracts, crude celery, and different pollen extracts. Specific IgE for
      celery was determined by using the CAP method. RESULTS: Twenty-two of 32 patients
      had a positive DBPCFC result. Two patients reacted to placebo, and 8 patients did
      not respond to the challenge. Of the nonresponders, 4 reacted to an open
      provocation with celery. The sensitivity of CAP determination for specific IgE (>
      or =0.7 kU/L) to celery in patients with a positive DBPCFC result was 73%, 48% to
      86% for SPTs (> or =3 mm) with commercial extracts, and 96% for prick-to-prick
      tests with crude celery. The positive predictive value of the SPT and CAP tests
      was between 87% and 96%, whereas the specificity and negative predictive values
      were poor. CONCLUSION: This study confirms the importance of celery as a food
      allergen for use in DBPCFCs. The SPT and CAP methods proved to be reliable for
      the diagnosis of a relevant allergy to celery in regard to sensitivity and
      positive predictive value but not to specificity and negative predictive value.

PMID- 10932084
TI  - Allergy caused by ingestion of zucchini (Cucurbita pepo): characterization of
      allergens and cross-reactivity to pollen and other foods.
AB  - BACKGROUND: Allergy to zucchini (Cucurbita pepo), a member of the Cucurbitaceae
      family, has not previously been reported. We examined 4 patients complaining of
      allergic symptoms, such as oral allergy syndrome, nausea, diarrhea, or pruritus,
      after the intake of zucchini. OBJECTIVE: After the confirmation of food allergy,
      we wanted to characterize zucchini allergens and examine possible cross-reactions
      to pollen and food. METHODS: The patients underwent skin prick and prick-to-prick
      testing with different allergens, including zucchini, latex, and birch, ragweed,
      and grass pollen. Moreover a double-blind, placebo-controlled, food challenge was
      performed to confirm food allergy. Total and specific serum IgE levels were
      determined by using CAP-FEIA and the enzyme allergosorbent test method (EAST),
      respectively. Proteins from zucchini reacting with patient IgE were detected by
      means of immunoblotting. To characterize cross-reacting IgE antibodies,
      immunoblot- and EAST-inhibition assays were carried out. RESULTS: All patients in
      this study had positive reactions to zucchini both in prick-to-prick tests and
      double-blind, placebo-controlled, food challenges. Specific serum IgE levels to
      zucchini were found in all cases. In blot- and EAST-inhibition assays IgE from
      two patients revealed binding to zucchini profilin at about 15 kd. Furthermore,
      in two cases, including one of the profilin-positive patients, IgE directed
      against cross-reacting carbohydrate determinants was detected. For one patient,
      no cross-reacting IgE could be found, but IgE from this patient reacted strongly
      with a zucchini protein at 17 kd. CONCLUSIONS: We report the first 4 cases of
      food allergy to zucchini. Zucchini allergens can cause systemic reactions and are
      at least partially heat stable. We suggest that allergy to zucchini can occur as
      a result of primary sensitization to zucchini, as well as to cross-reactions to
      the panallergen profilin and cross-reacting carbohydrate determinants.

PMID- 10932085
TI  - In vitro demonstration of IgE antibody to folate-albumin in anaphylaxis from
      folic acid.
AB  - BACKGROUND: Folic acid (the synthetic form of folate B vitamins in foods) is
      widely used in vitamin supplements. Anaphylaxis from ingestion or injection of
      folic acid suggests IgE antibody-mediated mechanisms, but this has not been
      demonstrated previously in vitro. OBJECTIVE: This study was conducted to better
      define the mechanism of folic acid hypersensitivity and cross-reactivity among
      folic acid congeners. METHODS: Skin testing was performed with folic acid
      congeners in a woman who developed anaphylaxis after ingestion of 2 different
      multivitamin preparations containing folic acid. In vitro immunologic serum
      studies were conducted using a folate-human serum albumin (HSA) conjugate
      prepared by a novel application of carbodiimide condensation. RESULTS: The
      patient had positive immediate-type skin test reactions to folic acid and several
      folate analogues including leucovorin (folinic acid). Urticaria developed during
      graded oral test dosing with leucovorin. Using a dot immunoblot assay or an ELISA
      for IgE antibody to folate-HSA, results of the patient's serum testing were
      positive, whereas results of sera from normal control subjects were negative, the
      first in vitro demonstration of IgE to a folic acid-protein conjugate. By ELISA,
      the positive result of the patient's serum was inhibited significantly by serum
      coincubation with folate-HSA, but not HSA or folic acid. CONCLUSIONS: Immediate
      hypersensitivity to folic acid and possibly other vitamins can be mediated by IgE
      antibody to conjugates formed between vitamins and self-proteins or polypeptides.
      Leucovorin can have clinically important immunologic cross-reactivity with folic
      acid. A diet rich in natural folates (pteroylpolyglutamates) appears useful as a
      management strategy for providing adequate nutrition to patients with folic acid
      hypersensitivity.

PMID- 10932086
TI  - Celery allergens in patients with positive double-blind placebo-controlled food
      challenge.
AB  - BACKGROUND: Recently, for the first time, allergy to celery was confirmed by
      double-blind placebo-controlled food challenge (DBPCFC). Api g 1, Api g 4, cross
      reactive carbohydrate determinants (CCD), and a 60 kDa allergen have been
      described as celery allergens. OBJECTIVE: To get insights in IgE responses of
      patients with a positive DBPCFC to celery tuber (celeriac) compared with patients
      with a negative challenge test. METHODS: Specific IgE to native and heated celery
      tuber and to recombinant Api g 1, the major celery allergen, were determined by
      enzyme allergosorbent test and immunoblotting. IgE binding to Api g 1, Api g 4,
      and CCD was confirmed by inhibition experiments that used recombinant Api g 1,
      recombinant Api g 4, pure N-glycans, and extracts of celeriac, lychee fruit, and
      pollens of birch, mugwort, and timothy grass as inhibitors. RESULTS:
      Immunoblotting with sera from 22 patients with a positive DBPCFC to celeriac
      confirmed the presence of known allergenic structures: The major allergen Api g 1
      (16 kDa) was recognized by IgE from 13 of 22 patients (59%). Another major
      allergen was CCD, determined by IgE reactivity in 12 of 22 patients (55%). Celery
      profilin, Api g 4, was recognized by IgE from 5 of 22 patients (23%). CONCLUSION:
      Our DBPCFC-positive patients exclusively presented IgE to known celery allergens,
      although the prevalences were slightly different than were previously reported.
      No obvious differences were found in patients with positive IgE antibody but
      negative challenge test. IgE binding to all 3 structures in celeriac extract was
      inhibited by birch pollen extract, whereas mugwort pollen extract could only
      inhibit IgE reactivity to Api g 4 and CCD. Inhibition experiments with a purified
      carbohydrate moiety clearly showed that the IgE epitope mannose-xylose-fucose
      glycan (Manalpha1-6[Xylbeta1-2]Manbeta1-4GlcNAcbeta1-4[ Fucalpha1-3]GlcNAc) or a
      closely related structure is present in celeriac extract and is important in
      patients with clinical allergy to celery.

PMID- 10932087
TI  - Identification of obeche wood (Triplochiton scleroxylon) allergens associated
      with occupational asthma.

PMID- 10932088
TI  - Allergy to pumpkin and cross-reactivity to other Cucurbitaceae fruits.

PMID- 10932089
TI  - Chlamydia pneumoniae antibodies and adult-onset asthma.

PMID- 10932092
TI  - To the heart of myofibril assembly.
AB  - One of the most fascinating examples of cytoskeletal assembly is the myofibril,
      the contractile structure of striated (i.e. skeletal and cardiac) muscle.
      Myofibrils are composed of repeating contractile units known as sarcomeres,
      perhaps the most highly ordered macromolecular structures in eukaryotic cells.
      When skeletal and cardiac muscle cells differentiate, thousands of structural and
      regulatory molecules assemble into the semicrystalline sarcomeric contractile
      units. As a consequence of this precise assembly, many different classes of
      proteins function together to convert the molecular interactions of actin and
      myosin efficiently into the macroscopic movements of contractile activity.

PMID- 10932093
TI  - Fibroblast-collagen-matrix contraction: growth-factor signalling and mechanical
      loading.
AB  - Fibroblast-collagen-matrix contraction provides a unique way to study reciprocal
      geometric and mechanical interactions between fibroblasts and extracellular
      matrix. Such interactions are difficult to appreciate or examine in routine cell
      culture because the culture surface is usually fixed in place. Forces exerted on
      collagen fibrils by cells cause isometric tension to develop in the cells if the
      collagen resists deformation; by contrast, the cells remain mechanically unloaded
      in the absence of matrix resistance. Recent evidence suggests that the state of
      cellular mechanical loading determines the mechanism that cells use to regulate
      contraction.

PMID- 10932094
TI  - Mitochondria as the central control point of apoptosis.
AB  - Mitochondria play a major role in apoptosis triggered by many stimuli. They
      integrate death signals through Bcl-2 family members and coordinate caspase
      activation through the release of cytochrome c as a result of the outer
      mitochondrial membrane becoming permeable. The mechanisms that lead to this
      permeability are not yet completely understood. Here, we attempt to summarize our
      current view of the mechanisms that lead to the efflux of many proteins from
      mitochondria during apoptosis and the role played by Bcl-2 family proteins in the
      control of this event.

PMID- 10932095
TI  - Signalling by semaphorin receptors: cell guidance and beyond.
AB  - Semaphorins are a large family of secreted or cell-bound signals, known to guide
      axons in developing nervous tissue. They are expressed in a variety of adult and
      embryonic tissues and are thought to have a broader spectrum of functions. Recent
      evidence suggests that semaphorins and their receptors play a key role in the
      control of cellular interactions, most likely in cell-cell repulsion. A subset of
      semaphorins interacts with neuropilins - cell-surface molecules lacking a
      signalling-competent cytoplasmic domain. Another large family of transmembrane
      molecules, namely plexins, bind specifically to semaphorins. Thus plexins, alone,
      or in association with neuropilins, behave as fully functional semaphorin
      receptors. The intracellular responses elicited by plexins are unknown, but their
      large cytoplasmic moiety, containing the strikingly conserved sex-plexin (SP)
      domain, is likely to trigger novel signal-transduction pathways.

PMID- 10932096
TI  - Breaking the COPI monopoly on Golgi recycling.
AB  - The unexpected discovery of a transport pathway from the Golgi to the endoplasmic
      reticulum (ER) independent of COPI coat proteins sheds light on how Golgi
      resident enzymes and protein toxins gain access to the ER from as far as the
      trans Golgi network. This new pathway provides an explanation for how membrane is
      recycled to allow for an apparent concentration of anterograde cargo at distinct
      stages of the secretory pathway. As signal-mediated COPI-dependent recycling also
      involves the concentration of resident proteins into retrograde COPI vesicles,
      the main bulk of lipids must be recycled, possibly through a COPI-independent
      pathway.

PMID- 10932098
TI  - Some reflections on science, industry and education.

PMID- 10932097
TI  - Separation anxiety at the centromere.
AB  - During mitosis, replicated sister-chromatids must maintain cohesion as they
      attach to the mitotic spindle. At anaphase, cohesion is lost simultaneously along
      the entire chromosome, releasing sisters from one another and allowing them to
      segregate to opposite poles. During meiosis, sisters separate in a two-step
      process. At anaphase of meiosis I, cohesion is lost along the chromosome arms but
      is maintained at centromeric regions. Not until meiosis II are sister chromatids
      able to break the connection at the centromere and separate away from one
      another. Recent studies suggest that the centromere exhibits dynamics that are
      very different compared with those of the chromatid arms during both mitosis and
      meiosis. This review discusses the nature of the specialized chromatid cohesion
      seen at the centromere.

PMID- 10932099
TI  - Supramolecular chemistry and technology
AB  - Supramolecular chemistry deals with the association of several chemical species,
      in an organized way and according to well defined purposes. Based on a molecular
      engineering approach, supramolecular structures can be designed from pre-formed
      building blocks, providing a promising route from chemistry to molecular
      nanotechnology. New supramolecular systems have been assembled in our laboratory
      with the use of bridging unities such as tetrapyridylporphyrins, porphyrazines
      and polypyrazines, connecting transition metal complexes and clusters. These
      systems display a very exciting electrochemical and catalytic behavior, and
      interact with DNA, generating 1O2 and leading to efficient oxidative clivage for
      photodynamic terapy applications. Molecular interfaces have been developed,
      exhibiting photocurrent response in the presence of visible-UV light, and
      rectifying properties in the presence of electroactive species. Successful
      applications of the supramolecular species in chemical and bio-sensors have been
      developed.

PMID- 10932100
TI  - Thin molecular films of supramolecular porphyrins.
AB  - A relevant series of symmetric supramolecular porphyrins has been obtained by
      attaching four [RuII(bipy)2Cl] groups to the pyridyl substituents of meso-tetra(4
      pyridyl)porphyrin and its metallated derivatives. These compounds display a rich
      electrochemistry and versatile catalytic, electrocatalytic and photochemical
      properties, associated with the ruthenium-bipyridine and the porphyrin complexes.
      These properties can be transferred to the electrodes by attaching thin molecular
      films of the compounds, by dip-coating, electrostatic assembly or
      electropolymerization. In this way, the interesting properties of those
      supermolecules and supramolecular assemblies can be used to prepare molecular
      devices and sensors.

PMID- 10932101
TI  - Supramolecular effects in dendritic systems containing photoactive groups
AB  - In this article are described dendritic structures containing photoactive groups
      at the surface or in the core. The observed supramolecular effects can be
      attributed to the nature of the photoactive group and their location in the
      dendritic architecture. The peripheric azobenzene groups in these dendrimeric
      compounds can be regarded as single residues that retain the spectroscopic and
      photochemical properties of free azobenzene moiety. The E and Z forms of higher
      generation dendrimer, functionalized with azobenzene groups, show different host
      ability towards eosin dye, suggesting the possibility of using such dendrimer in
      photocontrolled host-guest systems. The photophysical properties of many
      dendritic-bipyridine ruthenium complexes have been investigated. Particularly in
      aerated medium more intense emission and a longer excited-state lifetime are
      observed as compared to the parent unsubstituted bipyridine ruthenium complexes.
      These differences can be attributed to a shielding effect towards dioxygen
      quenching originated by the dendritic branches.

PMID- 10932102
TI  - Interactions between cationic liposomes and drugs or biomolecules.
AB  - Multiple uses for synthetic cationic liposomes composed of
      dioctadecyldimethylammonium bromide (DODAB) bilayer vesicles are presented. Drugs
      or biomolecules can be solubilized or incorporated in the cationic bilayers. The
      cationic liposomes themselves can act as antimicrobial agents causing death of
      bacteria and fungi at concentrations that barely affect mammalian cells in
      culture. Silica particles or polystyrene microspheres can be functionalized by
      coverage with DODAB bilayers or phospholipid monolayers. Negatively charged
      antigenic proteins can be carried by the cationic liposomes which generate a
      remarkable immunoadjuvant action. Nucleotides or DNA can be physically adsorbed
      to the cationic liposomes to be transferred to mammalian cells for gene therapy.
      An overview of the interactions between DODAB vesicles and some biomolecules or
      drugs clearly points out their versatility for useful applications in a near
      future.

PMID- 10932103
TI  - Intercalation compounds involving inorganic layered structures
AB  - Two-dimensional inorganic networks can shown intracrystalline reactivity, i.e.,
      simple ions, large species as Keggin ions, organic species, coordination
      compounds or organometallics can be incorporated in the interlayer region. The
      host-guest interaction usually causes changes in their chemical, catalytic,
      electronic and optical properties. The isolation of materials with interesting
      properties and making use of soft chemistry routes have given rise the
      possibility of industrial and technological applications of these compounds. We
      have been using several synthetic approaches to intercalate porphyrins and
      phthalocyanines into inorganic materials: smectite clays, layered double
      hydroxides and layered niobates. The isolated materials have been characterized
      by elemental and thermal analysis, X-ray diffraction, surface area measurements,
      scanning electronic microscopy, electronic and resonance Raman spectroscopies and
      EPR. The degree of layer stacking and the charge density of the matrices as well
      their acid-base nature were considered in our studies on the interaction between
      the macrocycles and inorganic hosts.

PMID- 10932105
TI  - Porphyrinosilica and metalloporphyrinosilica: hybrid organic-inorganic materials
      prepared by sol-gel processing
AB  - New materials porphyrinosilica and metalloporphyrinosilica template have been
      obtained by a sol-gel processing where functionalyzed porphyrins and
      metalloporphyrins "building blocks" were assembled into a three-dimensional
      silicate network. The optimized conditions for preparation of these materials are
      revised. The monomer precursors porphyrinopropylsilyl and
      metalloporphyrinopropylsilyl preparation reactions and subsequent one pot sol-gel
      processing with tetraethoxysilane are discussed. In the case of metalloporphyrins
      the nitrogen base coordinates to the central metal and acts as a template in the
      molecular imprinting technique. UV-visible absorption spectroscopy,
      thermogravimetric analysis, electron paramagnetic resonance, nuclear magnetic
      spectra, infrared spectra, luminescence spectra, surface area and electron
      spectroscopy imaging of the materials are used to characterize the prepared
      materials. The catalytic activities of these metalloporphyrinosilica-template are
      compared.

PMID- 10932104
TI  - Mimics of copper proteins: structural and functional aspects.
AB  - The importance of copper as an essential element can be estimated by the wide
      range of copper proteins and enzymes playing different roles in biological
      systems. In the last decades many bioinorganic studies were developed on mimetic
      complexes of copper-dependent proteins, in order to verify the interrelations
      between structural and functional properties of active copper centers. Among the
      most studied copper ion ligand, diimine compounds have deserved special attention
      due their flexibility, facility of preparation, and ability to stabilize both
      oxidation states of this metal. In our laboratory, we have been investigating
      some Schiff base copper complexes as mimics of different proteins, with emphasis
      on functional aspects, trying to elucidate mechanisms of reaction, based on
      proposed intermediary species, in addition to molecular shapes. Particularly,
      mimics of the copper-zinc superoxide dismutase, and of monooxigenases and
      oxidases exhibiting dicopper sites are discussed in this work.

PMID- 10932106
TI  - Supramolecular photochemistry and solar cells
AB  - Supramolecular photochemistry as well as solar cells are fascinating topics of
      current interest in Inorganic Photochemistry and very active research fields
      which have attracted wide attention in last two decades. A brief outline of the
      investigations in these fields carried out in our Laboratory of Inorganic
      Photochemistry and Energy Conversion is given here with no attempt of an
      exhaustive coverage of the literature. The emphasis is placed on recent work and
      information on the above mentioned subjects. Three types of supramolecular
      systems have been the focus of this work: (i) cage-type coordination compounds;
      (ii) second-sphere coordination compounds, exemplified by ion-pair photochemistry
      of cobalt complexes and (iii) covalently-linked systems. In the latter,
      modulation of the photoluminescence and photochemistry of some rhenium complexes
      are discussed. Solar energy conversion and development of thin-layer
      photoelectrochemical solar cells based on sensitization of nanocrystalline
      semiconductor films by some ruthenium polypyridyl complexes are presented as an
      important application that resulted from specifically engineered artificial
      assemblies.

PMID- 10932107
TI  - Zirconium phosphonate/1,4,5,8-naphthalenediimides self-assembled films
AB  - The formation and characterization of self-assembled films of zirconium
      phosphonate/N,N'-di(2-phosphonoethyl)-1,4,5,8-naphthalenediimide (DPN) is
      presented. The films were produced on glass substrates by deposition of
      alternating layers of Zr+4 and DPN. Films containing up to 16 layers on each side
      of the substrate were obtained and monitored by absorption spectroscopy and
      ellipsometry. When irradiated, the initially colorless films turned to a
      persistent pinky color reminiscent of that of DPN anion radical. These films are
      a promising material to the development of photovoltaic devices.

PMID- 10932108
TI  - Susceptible hosts: a resort for parasites right in the eye of the immune
      response.
AB  - Trypanosomatid protozoan parasites express an aggressive strategy of parasitism
      by infecting host macrophages and inducing extensive T-lymphocyte activation. One
      goal of such strategy is to drive the immune response of genetically susceptible
      hosts to a state of unresponsiveness regarding parasite killing. Unresponsiveness
      is achieved through different mechanisms, depending on the parasite species. In
      this brief review, recent findings on the molecular and cellular bases of the
      parasites' exploitation of host immune responses are discussed.

PMID- 10932109
TI  - Neonatal lupus syndrome: the heart as a target of the immune system.
AB  - Neonatal lupus erythematosus (NLE) is an auto-immune disease related to systemic
      lupus erythematosus (SLE). Unlike SLE it is not a spontaneous syndrome but rather
      an acquired one. In NLE the most common disease manifestations are a transient
      cutaneous lesion and cardiac conduction disturbances. The cutaneous lesions and
      other non-cardiac manifestations of NLE are transient and disappear about six
      months after birth, at the time when maternal antibodies disappear from the
      neonatal circulation. This fact suggests that maternal antibodies may cross the
      placenta leading to an inflammatory reaction in the fetal tissues. NLE is the
      principal cause of atria-ventricular block, when it is not associated with
      congenital birth defects. All the clinical studies to date correlate the heart
      block in NLE with the presence of certain types of circulating maternal
      antibodies, against the Ro/SSA nuclear proteins, in the serum of the newborn. In
      this paper we discuss animal models that have been developed by our and others
      groups to study the participation of the anti-Ro/SSA antibodies in the
      pathogenesis of the cardiac conduction blockades that occur in NLE.

PMID- 10932112
TI  - Geodesics without conjugate points and curvatures at infinity.
AB  - We study the asymptotic behavior of curvature and prove that the integral of
      curvature along a geodesic without conjugate points is nonpositive and some
      generalizations of Myers theorem and Cohn-Vossen's theorem. Some applications are
      also given.

PMID- 10932111
TI  - O(p + 1) x O(p + 1)-Invariant hypersurfaces with zero scalar curvature in
      euclidean space.
AB  - We use equivariant geometry methods to study and classify zero scalar curvature
      O(p + 1) x O(p + 1)-invariant hypersurfaces in R2p+2 with p > 1.

PMID- 10932110
TI  - Entry, dispersion and differentiation of microglia in the developing central
      nervous system.
AB  - Microglial cells within the developing central nervous system (CNS) originate
      from mesodermic precursors of hematopoietic lineage that enter the nervous
      parenchyma from the meninges, ventricular space and/or blood stream. Once in the
      nervous parenchyma, microglial cells increase in number and disperse throughout
      the CNS; these cells finally differentiate to become fully ramified microglial
      cells. In this article we review present knowledge on these phases of microglial
      development and the factors that probably influence them.

PMID- 10932113
TI  - Surfaces in E3 invariant under a one parameter group of isometries of E3.
AB  - We develop a convenient surface theory in E3 in order to apply it to the class of
      the surfaces invariant under a one-parameter group of isometries of E3. In this
      way we derive intrinsic characterizations along with several results of
      subclasses of this class of surfaces that satisfy certain preassigned properties.
      In the process all results are also effortlessly derived. Among these subclasses
      are those with surfaces; of constant mean curvature, of constant Gaussian
      curvature, isothermic, with constant difference or ratio of the principal
      curvatures.

PMID- 10932114
TI  - Dirac's aether in curved spacetime.
AB  - Proca's equations for two types of fields in a Dirac's aether with electric
      conductivity sigma are solved exactly. The Proca electromagnetic fields are
      assumed with cylindrical symmetry. The background is a static, curved spacetime
      whose spatial section is homogeneous and has the topology of either the three
      sphere S 3 or the projective three-space P 3. Simple relations between the range
      of Proca field lambda, the Universe radius R, the limit of photon rest mass
      mgamma and the conductivity sigma are written down.

PMID- 10932115
TI  - The current status of the New World monkey phylogeny.
AB  - Four DNA datasets were combined in tandem (6700 bp) and Maximum parsimony and
      Neighbor-Joining analyses were performed. The results suggest three groups
      emerging almost at the same time: Atelidae, Pitheciidae and Cebidae. The total
      analysis strongly supports the monophyly of the Cebidae family, grouping Aotus,
      Cebus and Saimiri with the small callitrichines. In the callitrichines, the data
      link Cebuela to Callithrix, place Callimico as a sister group of
      Callithrix/Cebuella, and show Saguinus to be the earliest offshoot of the
      callitrichines. In the family Pithecidae, Callicebus is the basal genus. Finally,
      combined molecular data showed congruent branching in the atelid clade, setting
      up Alouatta as the basal lineage and Brachyteles-Lagothrix as a sister group and
      the most derived branch. Two major points remain to be clarified in the
      platyrrhine phylogeny: (i) what is the exact branching pattern of Aotus, Cebus,
      Saimiri and the small callitrichines, and (ii), which two of these three
      lineages, pitheciines, atelines or cebids, are more closely related?

PMID- 10932117
TI  - A possible chelonian egg from the Brazilian late cretaceous.
AB  - This paper describes a possible fossil egg proceeding from the Bauru Group, Late
      Cretaceous of Parana Basin, Brazil. External morphology, dimensions, texture and
      shell ornamentation examined under electron microscopy show close resemblance to
      the Recent podocnemidid chelonian eggs. Association with bony material in the
      outcrop suggests that it is related to a species of Podocnemis. Computerized
      tomography reveals a high density outer region corresponding to the shell
      component layers, and successive layers with decreasing density towards the
      nucleus. An area of high density in the central region may represent remains of
      an embryo.

PMID- 10932116
TI  - Strategies by which some pathogenic trichomonads integrate diverse signals in the
      decision-making process.
AB  - The interaction between each one of Trichomonas vaginalis and Tritrichomonas
      foetus with their hosts is a complex process in which components associated to
      the cell surfaces of both parasites and host epithelial cells, and also to
      soluble components found in vaginal/urethral secretions, are involved. Either
      cytoadhesion or the cytotoxicity exerted by parasites to host cells can be
      dictated by virulence factors such as adhesins, cysteine proteinases, laminin
      binding proteins, integrins, integrin-like molecules, a cell detachment factor, a
      pore-forming protein, and glycosidases among others. How trichomonads manipulate
      informations from the extracellular medium, transduce such informations, and
      respond to them by stimulating the activities of some surface molecules and/or
      releasing enzymes are the aspects concerning trichomonal virulence which are here
      briefly reviewed and discussed.

PMID- 10932118
TI  - Geometry and kinematics of experimental antiformal stacks.
AB  - Sandbox experiments with different boundary conditions demonstrate that
      antiformal stacks result from a forward-breaking thrust sequence. An obstacle
      blocks forward thrust propagation and transfers the deformation back to the
      hinterland in a previously formed true duplex. In the hinterland, continued
      shortening causes faults to merge toward the tectonic transport direction until
      the older thrusts override the younger thrusts. In experiments using thin sand
      layers or high basal friction, shortening is accommodated by a cyclic process of
      thrusting, back rotation of the newly formed thrust combined with strong vertical
      strain, and nucleation of a new thrust. Continuous deformation produces an
      antiformal stack through progressive convergence of branch lines.

PMID- 10932119
TI  - The Sm-Nd isotopic method in the geochronology laboratory of the University of
      Brasilia.
AB  - Nd isotopes represent one of the best tools to investigate the processes involved
      in the evolution of the continental crust and mantle. This is due mainly to the
      similar geochemical behaviour of Sm and Nd, both light rare earth elements, which
      inhibits their fractionation during most varied geological processes. In order to
      carry out crustal evolution studies in central Brazil, the Sm-Nd isotopic method
      was implanted at the Geochronology Laboratory of the University of Brasilia. The
      Sm-Nd separation methodology is basically that described in Richard et al.
      (1976), with the addition of some improvements. In this study we describe in
      detail the methodology used in Brasilia. Precision and accuracy were checked with
      the international standards such as JB-3, BCR-1, BHVO-1 and La Jolla, and the
      following results were found: JB-3 (Nd=15.74 ppm and Sm=4.28 ppm), BCR-1
      (143Nd/144Nd=0.512647+/-8, Nd=28.73 ppm and Sm=6.66 ppm), BHVO-1 (Nd=24.83 ppm
      and Sm=6.2 ppm) and La Jolla (143Nd/144Nd=0.511835+/-14).

PMID- 10932120
TI  - The eolianites between Sanga do Cabral and Botucatu formations in Rio Grande do
      Sul State, Brazil.
AB  - This paper discusses the facies distribution of Mesozoic eolian sandstones
      between the Sanga do Cabral and Botucatu formations and also their contact
      relationships, in Sao Leopoldo area, State of Rio Grande do Sul (RS), southern
      Brazil. The main distinctive characteristics regarding these sandstones and
      formations are the mineralogical composition, paleocurrents and the occurrence of
      wet interdune deposits. These interdune deposits are characterized by frequent
      thin mudstone layers with mudcracks, ichnofossils and salt impressions. There are
      also some features that resemble plant fossils. The distinctive characteristics
      of these sequences to Sanga do Cabral and Botucatu formations allow us to suggest
      the informal name of Pedreira Sandstone, considering its type section, the
      Pedreira Cliff, at Sapucaia do Sul, RS.

PMID- 10932121
TI  - The quaternary geological history of the Santa Catarina Southeastern Region
      (Brazil).
AB  - This paper supply subsidies for Quaternary geological reconstruction of the
      southeastern State of Santa Catarina coast in Brazil, being based on detailed
      geological mapping supported by a series of drilling data, which allowed to
      establish a stratigraphical hierarchy of the sedimentary deposits. Among the
      mapped geological units stand out the extensive Pleistocene shallow marine sandy
      sediments, which are commonly referred as a barrier island - lagoonal
      depositional system. A drilling campaign done in the domain permitted the
      sampling of material for 14C datings, and the obtained data confirmed some
      previously assumed ages. The sequence of events, that originated the Holocene
      deposits, has been also reconstructed through drilling and 14C dating of the
      collected peat and shell samples. Finally, the main characteristics of the most
      promising mineral prospect of the area, represented by voluminous calcareous
      shell deposits associated with Holocene sediments, are also presented.

PMID- 10932122
TI  - Patterns of sediment dispersion coastwise the State of Bahia - Brazil.
AB  - Using the average directions of the main wave-fronts which approach the coast of
      Bahia State - coinciding with that of the main wind occurring in the area - and
      of their periods, we define a wave climate model based on the construction of
      refraction diagrams. The resulting model of sediment transport was able to
      reproduce, in a general way, the sediment dispersion patterns furnished by
      geomorphic indicators of the littoral drift. These dispersion patterns control
      the generation of different types of sediment accumulations and of coastal
      stretches under erosion. We demonstrate that the presence of the Abrolhos and
      Corumbau Point coral reefs is an important factor controlling the sediment
      dispersion patterns, since them act as a large protection against the waves
      action.

PMID- 10932123
TI  - Test instruments used by Journal of Music Therapy authors from 1984-1997.
AB  - Issues of the Journal of Music Therapy from 1984 to 1997 were selected to
      investigate the application of test instruments in music therapy research. All
      experimental and descriptive research articles were reviewed to determine if the
      methodology included test instruments. Other types of measurements-physiological
      measures, behavioral observations, computerized devices, and self-reports were
      excluded from the analysis. Test instruments were categorized as either
      published, unpublished, or researcher-constructed. A test instrument was
      "published" if, after a search in the "Test Review Locator" of the Buros Mental
      Measurements Web Site, a reference was found in one or more of the following
      publications-Mental Measurement Yearbooks, Tests in Print, or Test Critiques. A
      test was categorized as "unpublished" if the developer was cited in the JMT
      article but the test was not located in one or more of the above publications.
      All other test instruments were categorized as researcher-constructed tests
      designed for the specific study in the article. From 1984-1997, 220 articles were
      published in JMT. Approximately 83% (n = 183) of the total were experimental or
      descriptive research studies. Of the 183 articles research studies, 92 (50%)
      included a test instrument. Reviews of method sections of the 92 articles
      resulted in a listing of 115 different test instruments. Percentages of
      researcher-constructed tests, unpublished tests, and published tests were 25%,
      35%, and 40% respectively. Lists of tests document the all-encompassing range of
      client populations and the broad view of human behavior included in the practice
      of music as therapy. The Journal of Music Therapy, in addition to providing the
      latest research findings regarding the effectiveness of music as a therapeutic
      medium, provides an excellent source for updating information about the
      availability and applicability of test instruments for music therapy clinical
      practice and training.

PMID- 10932124
TI  - Music therapy assessment in school settings: a preliminary investigation.
AB  - The present investigation was undertaken in response to music therapists working
      in school settings for information relating to the availability of music therapy
      assessments and the feasibility of standardizing an assessment instrument for
      music therapists to use in school settings. Five research questions were
      identified, and the music therapy literature was surveyed to compile responses to
      those questions. Three different online data bases (ERIC, PsycINFO, and Article
      1st) were used, covering articles published between 1980 and 1997. Individual
      hand searches were done of the Arts in Psychotherapy, Journal of Music Therapy,
      Journal of Research in Music Education, Journal of the International Association
      of Music for the Handicapped, Music Therapy and Music Therapy Perspectives. The
      questions and responses were as follows: 1. Which music-based assessment tools
      are being used with children with disabilities? Little commonality in assessment
      tools being used by music therapists and researchers was discovered. Of the total
      41 studies, 20 (49%) reported using a "named" or "titled" assessment tool, and in
      the remaining 51% of studies, the authors reported using an untitled, and usually
      experimenter-designed, original assessment tool. 2. Have certain assessments been
      used in more than one study? Very limited replication of existing assessments was
      found. Of the 16 "named" assessments, only 3 were found to be used in more than
      one research study. 3. Are the actual assessments published along with the
      articles describing their use? Only 3 of the 20 studies using named assessments
      were published along with the journal article. Of the remaining 21 studies using
      original, experimenter-designed assessment tools, only 6 (28%) had the assessment
      instrument published with the article. 4. What is the primary purpose for using
      the assessment? Six primary purposes emerged from the review of the literature:
      to compare with data obtained from other assessment measures or from other
      populations (39%), as a baseline or pretest measure (29%), to determine
      eligibility for services or the receipt of treatment (12%), to determine the
      psychometric properties of the assessment (7%), suitability of the instrument for
      the given population (7%), and the identification of musical preferences (5%). 5.
      What are the musical or nonmusic elements being assessed? Musical elements were:
      music perception (37%), musical aptitude (29%), musical preferences (12%), and
      attention to/enjoyment of music (2%). Nonmusical behaviors/responses were: self
      expression (10%), motor responses (10%), behavioral responses (7%), cognitive
      development (2%), and acts of communication (2%). 6. What subject populations are
      being assessed? Subject populations were: children with developmental
      disabilities/mental retardation (44%), children with autism (10%), children with
      hearing impairments (17%), "psychiatric" clients or emotionally disturbed (22%),
      individuals described as "handicapped" (5%), individuals with physical
      disabilities (2%), and a student with a speech impairment (2%). Nondisabled
      individuals were also included in 12 of the aforementioned studies.

PMID- 10932126
TI  - First draft of genome sets new industry standards

PMID- 10932125
TI  - The effect of therapeutic music interventions on the behavior of hospitalized
      children in isolation: developing a contextual support model of music therapy.
AB  - The purpose of this study was to provide preliminary data that support or negate
      a contextual support model of music therapy. The contextual support model of
      music therapy, based on Skinner and Wellborn's (1994) motivational theory of
      coping, argues that therapeutic music environments possess elements of structure,
      autonomy support, and involvement that lead children to become more actively
      engaged with their environment. This study examined three basic suppositions of
      the theory: (a) that music interventions create supportive environments, (b) that
      music interventions increase children's active engagement, and (c) that
      relationships exist between supportive environments and engaging behavior. Ten
      pediatric oncology patients restricted to an isolated environment participated in
      the study. Participants, serving as their own controls, experienced four
      different environmental conditions. Each condition was videotaped to facilitate
      collection of environmental and behavioral data. Statistical analyses of these
      data revealed: (a) that the music environment possessed a significantly higher
      frequency of environmental support elements than other activities typically
      experienced by hospitalized children, (b) that therapeutic music interventions
      elicited significantly more engaging behaviors from hospitalized children than
      other hospital activities, (c) that positive behavioral effects of music
      interventions were not maintained in hospital experiences that followed the music
      session, and (d) that environmental support elements were related to some
      positive behaviors but these behaviors were not consistent across environments.

PMID- 10932127
TI  - Rational limits on genomic patents.

PMID- 10932128
TI  - The bioweapons convention's impact on bioindustry.

PMID- 10932129
TI  - BEP programme.

PMID- 10932131
TI  - Reply to 'Ubiquitin/proteasome system'

PMID- 10932130
TI  - Ubiquitin/proteasome system.

PMID- 10932132
TI  - GMO roundup

PMID- 10932134
TI  - Lentiviruses for stable gene therapy

PMID- 10932133
TI  - Joint genome announcement

PMID- 10932136
TI  - Bacillus identity crisis

PMID- 10932135
TI  - Telomerase linked with cancer risk?

PMID- 10932138
TI  - Enhanced Alzheimer's diagnostics

PMID- 10932139
TI  - Engineering novel carotenoids

PMID- 10932137
TI  - Transgenic blood suckers

PMID- 10932140
TI  - Millennium and Aventis in unique pact.

PMID- 10932141
TI  - CD18 trials disappoint again.

PMID- 10932142
TI  - Genomics company formed from Framingham heart study.

PMID- 10932144
TI  - Researchers discuss NIH's nanotechnology initiative.

PMID- 10932143
TI  - French refuse to implement biotech patent directive.

PMID- 10932145
TI  - British biotech redefines itself.

PMID- 10932146
TI  - Imaging Alzheimer's amyloid.

PMID- 10932147
TI  - A kaleidoscope of carotenoids.

PMID- 10932148
TI  - The possibilities/perplexities of stem cells.

PMID- 10932149
TI  - Biological software for materials engineering.

PMID- 10932150
TI  - Biopharmaceutical benchmarks.

PMID- 10932151
TI  - Emerging themes in medicinal glycoscience.
AB  - The recognition of complex carbohydrates and glycoconjugates as mediators of
      important biological processes has stimulated investigation into their
      therapeutic potential. New approaches for the simplification of glycoconjugate
      synthesis are overcoming the limitations of existing methods and providing a
      diverse array of these biomolecules. As the accessibility of glycoconjugates
      increases, carbohydrate-based constructs are becoming available for analysis as
      medicinal agents in a wide range of therapies.

PMID- 10932152
TI  - Novel hydroxycarotenoids with improved antioxidative properties produced by gene
      combination in Escherichia coli.
AB  - We have used combinatorial biosynthesis to synthesize novel lipophilic
      carotenoids that are powerful cellular antioxidants. By co-expressing three
      different carotenoid desaturases in combination with a carotenoid hydratase, a
      cyclase, and a hydroxylase on compatible plasmids in Escherichia coli, we
      synthesized four novel carotenoids not previously detected in biological material
      or chemically synthesized. Their identification was based on their relative
      retention times on HPLC, spectroscopic properties, molecular weights, number of
      hydroxy groups, and 1H-NMR spectra. The carotenoids were designated as 1-HO-3',
      4'-didehydrolycopene, 3, 1'-(HO)2-gamma-carotene, 1,1'-(HO)2-3, 4, 3', 4'
      tetradehydrolycopene, and 1, 1'-(HO)2-3, 4-didehydrolycopene. These novel acyclic
      derivatives differ from structurally related compounds by extension of the
      conjugated polyene chain as well as additional hydroxy groups at position C-1'.
      We determined their antioxidative activity in a liposome-membrane model system,
      which showed that their ability to protect against photooxidation and radical
      mediated peroxidation reactions was linked to the length of the conjugated double
      bond system and the presence of a single hydroxy group. The protection of
      membrane degradation was superior to the related 1-HO and 1, 1'-(HO)2 lycopene
      derivatives, making them interesting pharmaceutical candidates.

PMID- 10932154
TI  - Recombining germline-derived CDR sequences for creating diverse single-framework
      antibody libraries.
AB  - We constructed a single-chain Fv antibody library that permits human
      complementarity-determining region (CDR) gene fragments of any germline to be
      incorporated combinatorially into the appropriate positions of the variable
      region frameworks VH-DP47 and VL-DPL3. A library of 2 x 109 independent
      transformants was screened against haptens, peptides, carbohydrates, and
      proteins, and the selected antibody fragments exhibited dissociation constants in
      the subnanomolar range. The antibody genes in this library were built on a single
      master framework into which diverse CDRs were allowed to recombine. These CDRs
      were sampled from in vivo-processed gene sequences, thus potentially optimizing
      the levels of correctly folded and functional molecules, and resulting in a
      molecule exhibiting a lower computed immunogenicity compared to naive
      immunoglobulins. Using the modularized assembly process to incorporate foreign
      sequences into an immunoglobulin scaffold, it is possible to vary as many as six
      CDRs at the same time, creating genetic and functional variation in antibody
      molecules.

PMID- 10932153
TI  - Genetic selection for dissociative inhibitors of designated protein-protein
      interactions.
AB  - Many biological processes rely on protein-protein interactions. These processes
      include signal transduction, cell cycle regulation, gene regulation, and viral
      assembly and replication. Moreover, many proteins and enzymes manifest their
      function as oligomers. We describe here an efficient means to sift through large
      combinatorial libraries and identify molecules that block the interaction of
      target proteins in vivo. The power of this approach is demonstrated by the
      identification of nine-residue peptides from a combinatorial library that inhibit
      the intracellular dimerization of HIV-1 protease. Fewer than 1 in 106 peptides do
      so. In vitro biochemical analyses of one such peptide demonstrate that it acts by
      dissociating HIV-1 protease into monomers, which are inactive catalysts.
      Inhibition is enhanced further by dimerizing the peptide. This approach enables
      the facile identification of new molecules that control cellular processes.

PMID- 10932155
TI  - Environmentally safe production of 7-aminodeacetoxycephalosporanic acid (7-ADCA)
      using recombinant strains of Acremonium chrysogenum.
AB  - Medically useful semisynthetic cephalosporins are made from 7
      aminodeacetoxycephalosporanic acid (7-ADCA) or 7-aminocephalosporanic acid (7
      ACA). Here we describe a new industrially amenable bioprocess for the production
      of the important intermediate 7-ADCA that can replace the expensive and
      environmentally unfriendly chemical method classically used. The method is based
      on the disruption and one-step replacement of the cefEF gene, encoding the
      bifunctional expandase/hydroxylase activity, of an actual industrial
      cephalosporin C production strain of Acremonium chrysogenum. Subsequent cloning
      and expression of the cefE gene from Streptomyces clavuligerus in A. chrysogenum
      yield recombinant strains producing high titers of deacetoxycephalosporin C
      (DAOC). Production level of DAOC is nearly equivalent (75-80%) to the total beta
      lactams biosynthesized by the parental overproducing strain. DAOC deacylation is
      carried out by two final enzymatic bioconversions catalyzed by D-amino acid
      oxidase (DAO) and glutaryl acylase (GLA) yielding 7-ADCA. In contrast to the data
      reported for recombinant strains of Penicillium chrysogenum expressing ring
      expansion activity, no detectable contamination with other cephalosporin
      intermediates occurred.

PMID- 10932156
TI  - Reduction of liver Fas expression by an antisense oligonucleotide protects mice
      from fulminant hepatitis.
AB  - Aberrant apoptosis-mediated cell death is believed to result in a number of
      different human diseases. For example, excessive apoptosis in the liver can
      result in fulminant and autoimmune forms of hepatitis. We have explored the
      possibility that inhibition of Fas expression in mice would reduce the severity
      of fulminant hepatitis. To do this, we have developed a chemically modified 2'-O
      (2-methoxy)ethyl antisense oligonucleotide (ISIS 22023) inhibitor of mouse Fas
      expression. In tissue culture, this oligonucleotide induced a reduction in Fas
      mRNA expression that was both concentration- and sequence-specific. In Balb/c
      mice, dosing with ISIS 22023 reduced Fas mRNA and protein expressions in liver by
      90%. The ID50 for this response was 8-10 mg kg-1 daily dosing, and the reduction
      was highly dependent on oligonucleotide sequence, oligonucleotide concentration
      in liver, and treatment time. Pretreatment with ISIS 22023 completely protected
      mice from fulminant hepatitis induced by agonistic Fas antibody, by a mechanism
      entirely consistent with an oligonucleotide antisense mechanism of action. In
      addition, oligonucleotide-mediated suppression of Fas expression reduced the
      severity of acetaminophen-mediated fulminant hepatitis, but was without effect on
      concanavalin A-mediated hepatitis. Our results demonstrate that 2'-O-(2
      methoxy)ethyl containing antisense oligonucleotides targeting Fas can exert in
      vivo pharmacological activity in liver, and suggest that oligonucleotide
      inhibitors of Fas may be useful in the treatment of human liver disease.

PMID- 10932157
TI  - Targeting alzheimer amyloid plaques in vivo.
AB  - The only definitive diagnosis for Alzheimer disease (AD) at present is postmortem
      observation of neuritic plaques and neurofibrillary tangles in brain sections.
      Radiolabeled amyloid-beta peptide (Abeta), which has been shown to label neuritic
      plaques in vitro, therefore could provide a diagnostic tool if it also labels
      neuritic plaques in vivo following intravenous injection. In this study, we show
      that the permeability of Abeta at the blood-brain barrier can be increased by at
      least twofold through covalent modification with the naturally occurring
      polyamine, putrescine. We also show that, following intravenous injection,
      radiolabeled, putrescine-modified Abeta labels amyloid deposits in vivo in a
      transgenic mouse model of AD, as well as in vitro in human AD brain sections.
      This technology, when applied to humans, may be used to detect plaques in vivo,
      allowing early diagnosis of the disease and therapeutic intervention before
      cognitive decline occurs.

PMID- 10932158
TI  - Phage display of peptide epitopes from HIV-1 elicits strong cytolytic responses.
AB  - Although much effort has been expended on evaluating recombinant proteins and
      synthetic peptides as immunogens, they have generally proved incapable of
      inducing an efficient cytotoxic T-cell (CTL) response. Filamentous bacteriophage
      fd can display multiple copies of foreign peptides in the N-terminal region of
      its major coat protein pVIII, 2,700 copies of which make up the virus capsid.
      Here we show that fd virions displaying peptide RT2 (ILKEPVHGV), corresponding to
      residues 309-317 of the reverse transcriptase (RTase) of HIV-1, are able to prime
      a CTL response specific for this HIV-1 epitope in human cell lines. Successful
      priming also requires a T-helper epitope, pep23 (KDSWTVNDIQKLVGK), corresponding
      to residues 249-263 of HIV-1 RTase. Supplying this by displaying it on either the
      same or a separate bacteriophage virion led to activation of antigen-specific
      CD4+ T cells. Likewise, HLA-A2 transgenic mice immunized with bacteriophage
      virions displaying peptide RT2 were shown to mount an effective, specific anti
      HIV-RT2 CTL response. This unexpected ability to elicit a designated cytolytic T
      cell response, in addition to a B-cell response, has important implications for
      access to the class I major histocompatibility complex (MHC) loading compartment
      and the development of recombinant vaccines.

PMID- 10932159
TI  - High-performance affinity beads for identifying drug receptors.
AB  - We have developed a method using novel latex beads for rapid identification of
      drug receptors using affinity purification. Composed of a glycidylmethacrylate
      (GMA) and styrene copolymer core with a GMA polymer surface, the beads minimize
      nonspecific protein binding and maximize purification efficiency. We demonstrated
      their performance by efficiently purifying FK506-binding protein using FK506
      conjugated beads, and found that the amount of material needed was significantly
      reduced compared with previous methods. Using the latex beads, we identified a
      redox-related factor, Ref-1, as a target protein of an anti-NF-kappaB drug,
      E3330, demonstrating the existence of a new class of receptors of anti-NF-kappaB
      drugs. Our results suggest that the latex beads could provide a tool for the
      identification and analysis of drug receptors and should therefore be useful in
      drug development.

PMID- 10932160
TI  - Pulsed electric fields for selection of hematopoietic cells and depletion of
      tumor cell contaminants.
AB  - Purging of tumor cells and selection of stem cells are key technologies for
      enabling stem cell transplantation and stem cell gene therapy. Here we report a
      strategy for cell selection based on physical properties of the cells. Exposing
      cells to an external pulsed electric field (PEF) increases the natural potential
      difference across the cell membrane until a critical threshold is reached and
      pore formation occurs, resulting in fatal perturbation of cell physiology.
      Attaining this threshold is a function of the applied field intensity and cell
      size, with larger cells porated at lower field intensities than smaller cells.
      Since hematopoietic stem cells are smaller than other hematopoietic cells and
      tumor cells, we found that exposure of peripheral blood mononuclear cells (PBMCs)
      to PEFs caused stepwise elimination of monocytes without affecting the function
      of smaller lymphocyte populations. Mobilized peripheral blood exposed to PEFs was
      enriched for CD34+/CD38- cells and stem cell function was preserved. Furthermore,
      PEF treatment was able to selectively purge blood preparations of tumor cells and
      eradicate transplantable tumor.

PMID- 10932161
TI  - Metabolic engineering of astaxanthin production in tobacco flowers.
AB  - Using metabolic engineering, we have modified the carotenoid biosynthesis pathway
      in tobacco (Nicotiana tabacum) to produce astaxanthin, a red pigment of
      considerable economic value. To alter the carotenoid pathway in chromoplasts of
      higher plants, the cDNA of the gene CrtO from the alga Haematococcus pluvialis,
      encoding beta-carotene ketolase, was transferred to tobacco under the regulation
      of the tomato Pds (phytoene desaturase) promoter. The transit peptide of PDS from
      tomato was used to target the CRTO polypeptide to the plastids. Chromoplasts in
      the nectary tissue of transgenic plants accumulated (3S,3'S) astaxanthin and
      other ketocarotenoids, changing the color of the nectary from yellow to red. This
      accomplishment demonstrates that plants can be used as a source of novel
      carotenoid pigments such as astaxanthin. The procedures described in this work
      can serve as a platform technology for future genetic manipulations of
      pigmentation of fruits and flowers of horticultural and floricultural importance.

PMID- 10932162
TI  - Enhancement of transfection by physical concentration of DNA at the cell surface.
AB  - Efficient DNA transfection is critical for biological research and new clinical
      therapies, but the mechanisms responsible for DNA uptake are unknown. Current
      nonviral transfection methods, empirically designed to maximize DNA complexation
      and/or membrane fusion, are amenable to enhancement by a variety of chemicals.
      These chemicals include particulates, lipids, and polymer complexes that optimize
      DNA complexation/condensation, membrane fusion, endosomal release, or nuclear
      targeting, which are the presumed barriers to gene delivery. Most chemical
      enhancements produce a moderate increase in gene delivery and a limited increase
      in gene expression. As a result, the efficiency of transfection and level of gene
      expression after nonviral DNA delivery remain low, suggesting the existence of
      additional unidentified barriers. Here, we tested the hypothesis that DNA
      transfection efficiency is limited by a simple physical barrier: low DNA
      concentration at the cell surface. We used dense silica nanoparticles to
      concentrate DNA-vector (i.e. DNA-transfection reagent) complexes at the surface
      of cell monolayers; manipulations that increased complex concentration at the
      cell surface enhanced transfection efficiency by up to 8.5-fold over the best
      commercially available transfection reagents. We predict that manipulations aimed
      at optimizing DNA complexation or membrane fusion have a fundamental physical
      limit; new methods designed to increase transfection efficiency must increase DNA
      concentration at the target cell surface without adding to the toxicity.

PMID- 10932163
TI  - Heritable gene silencing in Drosophila using double-stranded RNA.
AB  - RNA-mediated interference (RNAi) is a recently discovered method to determine
      gene function in a number of organisms, including plants, nematodes, Drosophila,
      zebrafish, and mice. Injection of double-stranded RNA (dsRNA) corresponding to a
      single gene into organisms silences expression of the specific gene. Rapid
      degradation of mRNA in affected cells blocks gene expression. Despite the promise
      of RNAi as a tool for functional genomics, injection of dsRNA interferes with
      gene expression transiently and is not stably inherited. Consequently, use of
      RNAi to study gene function in the late stages of development has been limited.
      It is particularly problematic for development of disease models that reply on
      post-natal individuals. To circumvent this problem in Drosophila, we have
      developed a method to express dsRNA as an extended hairpin-loop RNA. This method
      has recently been successful in generating RNAi in the nematode Caenorhabditis
      elegans. The hairpin RNA is expressed from a transgene exhibiting dyad symmetry
      in a controlled temporal and spatial pattern. We report that the stably inherited
      transgene confers specific interference of gene expression in embryos, and
      tissues that give rise to adult structures such as the wings, legs, eyes, and
      brain. Thus, RNAi can be adapted to study late-acting gene function in
      Drosophila. The success of this approach in Drosophila and C. elegans suggests
      that a similar approach may prove useful to study gene function in higher
      organisms for which transgenic technology is available.

PMID- 10932164
TI  - European patent oppositions and biotechnology.

PMID- 10932166
TI  - People

PMID- 10932165
TI  - In silico genomes

PMID- 10932167
TI  - New products

PMID- 10932168
TI  - The end of the beginning.

PMID- 10932170
TI  - Tailoring vectors through DNA shuffling.

PMID- 10932169
TI  - Hunting in the calm before the storm.

PMID- 10932172
TI  - TOUCHINGbase

PMID- 10932171
TI  - Subdividing the metamere: one signal, two outcomes.

PMID- 10932174
TI  - Of sex and gender.

PMID- 10932173
TI  - Genetic homogeneity of Icelanders: fact or fiction?

PMID- 10932175
TI  - Hot-stop PCR: a simple and general assay for linear quantitation of allele
      ratios.
AB  - We have developed a simple, quantitative assay for measurement of allele ratios
      that circumvents the problem of heteroduplex formation skewing the results of
      restriction endonuclease digestion of PCR products. This assay, 'hot-stop PCR',
      involves addition of a radiolabelled PCR primer at the final cycle. We applied
      the assay to analysis of loss of imprinting (LOI) of the insulin-like growth
      factor II gene (IGF2) in tumours.

PMID- 10932176
TI  - The NOTCH4 locus is associated with susceptibility to schizophrenia.
AB  - Linkage disequilibrium mapping of the MHC region in 80 British parent-offspring
      trios showed that NOTCH4 was highly associated with schizophrenia. The A-->G
      substitution in the promoter region and the (CTG)n repeat in exon 1 of NOTCH4 may
      be candidate sites conferring susceptibility to schizophrenia.

PMID- 10932177
TI  - How it all happened

PMID- 10932178
TI  - The roads from phenotypic variation to gene discovery: mutagenesis versus QTLs.
AB  - In model organisms, chemical mutagenesis provides a powerful alternative to
      natural, polygenic variation (for example, quantitative trait loci (QTLs)) for
      identifying functional pathways and complex disease genes. Despite recent
      progress in QTLs, we expect that mutagenesis is will ultimately prove more
      effective because the prospects of gene identification are high and every gene
      affecting a trait is potentially a target.

PMID- 10932179
TI  - Amino-terminal fragments of mutant huntingtin show selective accumulation in
      striatal neurons and synaptic toxicity.
AB  - Huntington disease (HD) is caused by expansion of a glutamine repeat in the amino
      terminal region of huntingtin. Despite its widespread expression, mutant
      huntingtin induces selective neuronal loss in striatal neurons. Here we report
      that, in mutant mice expressing HD repeats, the production and aggregation of N
      terminal huntingtin fragments preferentially occur in HD-affected neurons and
      their processes and axonal terminals. N-terminal fragments of mutant huntingtin
      form aggregates and induce neuritic degeneration in cultured striatal neurons. N
      terminal mutant huntingtin also binds to synaptic vesicles and inhibits their
      glutamate uptake in vitro. The specific processing and accumulation of toxic
      fragments of N-terminal huntingtin in HD-affected striatal neurons, especially in
      their neuronal processes and axonal terminals, may contribute to the selective
      neuropathology of HD.

PMID- 10932180
TI  - Mesp2 initiates somite segmentation through the Notch signalling pathway.
AB  - The Notch-signalling pathway is important in establishing metameric pattern
      during somitogenesis. In mice, the lack of either of two molecules involved in
      the Notch-signalling pathway, Mesp2 or presenilin-1 (Ps1), results in contrasting
      phenotypes: caudalized versus rostralized vertebra. Here we adopt a genetic
      approach to analyse the molecular mechanism underlying the establishment of
      rostro-caudal polarity in somites. By focusing on the fact that expression of a
      Notch ligand, Dll1, is important for prefiguring somite identity, we found that
      Mesp2 initiates establishment of rostro-caudal polarity by controlling two Notch
      signalling pathways. Initially, Mesp2 activates a Ps1-independent Notch
      signalling cascade to suppress Dll1 expression and specify the rostral half of
      the somite. Ps1-mediated Notch-signalling is required to induce Dll1 expression
      in the caudal half of the somite. Therefore, Mesp2- and Ps1-dependent activation
      of Notch-signalling pathways might differentially regulate Dll1 expression,
      resulting in the establishment of the rostro-caudal polarity of somites.

PMID- 10932181
TI  - Human microphthalmia associated with mutations in the retinal homeobox gene
      CHX10.
AB  - Isolated human microphthalmia/anophthalmia, a cause of congenital blindness, is a
      clinically and genetically heterogeneous developmental disorder characterized by
      a small eye and other ocular abnormalities. Three microphthalmia/anophthalmia
      loci have been identified, and two others have been inferred by the co
      segregation of translocations with the phenotype. We previously found that mice
      with ocular retardation (the or-J allele), a microphthalmia phenotype, have a
      null mutation in the retinal homeobox gene Chx10 (refs 7,8). We report here the
      mapping of a human microphthalmia locus on chromosome 14q24.3, the cloning of
      CHX10 at this locus and the identification of recessive CHX10 mutations in two
      families with non-syndromic microphthalmia (MIM 251600), cataracts and severe
      abnormalities of the iris. In affected individuals, a highly conserved arginine
      residue in the DNA-recognition helix of the homeodomain is replaced by glutamine
      or proline (R200Q and R200P, respectively). Identification of the CHX10 consensus
      DNA-binding sequence (TAATTAGC) allowed us to demonstrate that both mutations
      severely disrupt CHX10 function. Human CHX10 is expressed in progenitor cells of
      the developing neuroretina and in the inner nuclear layer of the mature retina.
      The strong conservation in vertebrates of the CHX10 sequence, pattern of
      expression and loss-of-function phenotypes demonstrates the evolutionary
      importance of the genetic network through which this gene regulates eye
      development.

PMID- 10932182
TI  - Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice
      expressing mutant (P301L) tau protein.
AB  - Neurofibrillary tangles (NFT) composed of the microtubule-associated protein tau
      are prominent in Alzheimer disease (AD), Pick disease, progressive supranuclear
      palsy (PSP) and corticobasal degeneration (CBD). Mutations in the gene (Mtapt)
      encoding tau protein cause frontotemporal dementia and parkinsonism linked to
      chromosome 17 (FTDP-17), thereby proving that tau dysfunction can directly result
      in neurodegeneration. Expression of human tau containing the most common FTDP-17
      mutation (P301L) results in motor and behavioural deficits in transgenic mice,
      with age- and gene-dose-dependent development of NFT. This phenotype occurred as
      early as 6.5 months in hemizygous and 4.5 months in homozygous animals. NFT and
      Pick-body-like neuronal lesions occurred in the amygdala, septal nuclei, pre
      optic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and
      spinal cord, with tau-immunoreactive pre-tangles in the cortex, hippocampus and
      basal ganglia. Areas with the most NFT had reactive gliosis. Spinal cord had
      axonal spheroids, anterior horn cell loss and axonal degeneration in anterior
      spinal roots. We also saw peripheral neuropathy and skeletal muscle with
      neurogenic atrophy. Brain and spinal cord contained insoluble tau that co
      migrated with insoluble tau from AD and FTDP-17 brains. The phenotype of mice
      expressing P301L mutant tau mimics features of human tauopathies and provides a
      model for investigating the pathogenesis of diseases with NFT.

PMID- 10932183
TI  - EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in
      patients with Wolcott-Rallison syndrome.
AB  - Wolcott-Rallison syndrome (WRS) is a rare, autosomal recessive disorder
      characterized by permanent neonatal or early infancy insulin-dependent diabetes.
      Epiphyseal dysplasia, osteoporosis and growth retardation occur at a later age.
      Other frequent multisystemic manifestations include hepatic and renal
      dysfunction, mental retardation and cardiovascular abnormalities. On the basis of
      two consanguineous families, we mapped WRS to a region of less than 3 cM on
      chromosome 2p12, with maximal evidence of linkage and homozygosity at 4
      microsatellite markers within an interval of approximately 1 cM. The gene
      encoding the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3)
      resides in this interval; thus we explored it as a candidate. We identified
      distinct mutations of EIF2AK3 that segregated with the disorder in each of the
      families. The first mutation produces a truncated protein in which the entire
      catalytic domain is missing. The other changes an amino acid, located in the
      catalytic domain of the protein, that is highly conserved among kinases from the
      same subfamily. Our results provide evidence for the role of EIF2AK3 in WRS. The
      identification of this gene may provide insight into the understanding of the
      more common forms of diabetes and other pathologic manifestations of WRS.

PMID- 10932184
TI  - Adaptive evolution of the tumour suppressor BRCA1 in humans and chimpanzees.
      Australian Breast Cancer Family Study.
AB  - Mutations in BRCA1 (ref. 1) confer an increased risk of female breast cancer. In
      a genome-wide scan of linkage disequilibrium (LD), a high level of LD was
      detected among microsatellite markers flanking BRCA1 (ref. 3), raising the
      prospect that positive natural selection may have acted on this gene. We have
      used the predictions of evolutionary genetic theory to investigate this further.
      Using phylogeny-based maximum likelihood analysis of the BRCA1 sequences from
      primates and other mammals, we found that the ratios of replacement to silent
      nucleotide substitutions on the human and chimpanzee lineages were not different
      from one another (P=0.8), were different from those of other primate lineages
      (P=0.004) and were greater than 1 (P=0.04). This is consistent with the historic
      occurrence of positive darwinian selection pressure on the BRCA1 protein in the
      human and chimpanzee lineages. Analysis of genetic variation in a sample of
      female Australians of Northern European origin showed evidence for Hardy-Weinberg
      (HW) disequilibrium at polymorphic sites in BRCA1, consistent with the
      possibility that natural selection is affecting genotype frequencies in modern
      Europeans. The clustering of between-species variation in the region of the gene
      encoding the RAD51-interaction domain of BRCA1 suggests the maintenance of
      genomic integrity as a possible target of selection.

PMID- 10932185
TI  - Ryk-deficient mice exhibit craniofacial defects associated with perturbed Eph
      receptor crosstalk.
AB  - Secondary palate formation is a complex process that is frequently disturbed in
      mammals, resulting in the birth defect cleft palate. Gene targeting has
      identified components of cytokine/growth factor signalling systems such as Tgf
      alpha/Egfr, Eph receptors B2 and B3 (Ephb2 and Ephb3, respectively), Tgf-beta2,
      Tgf-beta3 and activin-betaA (ref. 3) as regulators of secondary palate
      development. Here we demonstrate that the mouse orphan receptor 'related to
      tyrosine kinases' (Ryk) is essential for normal development and morphogenesis of
      craniofacial structures including the secondary palate. Ryk belongs to a subclass
      of catalytically inactive, but otherwise distantly related, receptor protein
      tyrosine kinases (RTKs). Mice homozygous for a null allele of Ryk have a
      distinctive craniofacial appearance, shortened limbs and postnatal mortality due
      to feeding and respiratory complications associated with a complete cleft of the
      secondary palate. Consistent with cleft palate phenocopy in Ephb2/Ephb3-deficient
      mice and the role of a Drosophila melanogaster Ryk orthologue, Derailed, in the
      transduction of repulsive axon pathfinding cues, our biochemical data implicate
      Ryk in signalling mediated by Eph receptors and the cell-junction-associated Af-6
      (also known as Afadin). Our findings highlight the importance of signal crosstalk
      between members of different RTK subfamilies.

PMID- 10932186
TI  - Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused
      by mutation of ROR2.
AB  - The autosomal recessive form of Robinow syndrome (RRS; MIM 268310) is a severe
      skeletal dysplasia with generalized limb bone shortening, segmental defects of
      the spine, brachydactyly and a dysmorphic facial appearance. We previously mapped
      the gene mutated in RRS to chromosome 9q22 (ref. 4), a region that overlaps the
      locus for autosomal dominant brachydactyly type B (refs 5,6). The recent
      identification of ROR2, encoding an orphan receptor tyrosine kinase, as the gene
      mutated in brachydactyly type B (BDB1; ref. 7) and the mesomelic dwarfing in mice
      homozygous for a lacZ and/or a neo insertion into Ror2 (refs 8,9) made this gene
      a candidate for RRS. Here we report homozygous missense mutations in both
      intracellular and extracellular domains of ROR2 in affected individuals from 3
      unrelated consanguineous families, and a nonsense mutation that removes the
      tyrosine kinase domain and all subsequent 3' regions of the gene in 14 patients
      from 7 families from Oman. The nature of these mutations suggests that RRS is
      caused by loss of ROR2 activity. The identification of mutations in three
      distinct domains (containing Frizzled-like, kringle and tyrosine kinase motifs)
      indicates that these are all essential for ROR2 function.

PMID- 10932187
TI  - Mutation of the gene encoding the ROR2 tyrosine kinase causes autosomal recessive
      Robinow syndrome.
AB  - Robinow syndrome is a short-limbed dwarfism characterized by abnormal
      morphogenesis of the face and external genitalia, and vertebral segmentation. The
      recessive form of Robinow syndrome (RRS; OMIM 268310), particularly frequent in
      Turkey, has a high incidence of abnormalities of the vertebral column such as
      hemivertebrae and rib fusions, which is not seen in the dominant form. Some
      patients have cardiac malformations or facial clefting. We have mapped a gene for
      RRS to 9q21-q23 in 11 families. Haplotype sharing was observed between three
      families from Turkey, which localized the gene to a 4. 9-cM interval. The gene
      ROR2, which encodes an orphan membrane-bound tyrosine kinase, maps to this
      region. Heterozygous (presumed gain of function) mutations in ROR2 were
      previously shown to cause dominant brachydactyly type B (BDB; ref. 7). In
      contrast, Ror2-/- mice have a short-limbed phenotype that is more reminiscent of
      the mesomelic shortening observed in RRS. We detected several homozygous ROR2
      mutations in our cohort of RRS patients that are located upstream from those
      previously found in BDB. The ROR2 mutations present in RRS result in premature
      stop codons and predict nonfunctional proteins.

PMID- 10932188
TI  - Mutations of PVRL1, encoding a cell-cell adhesion molecule/herpesvirus receptor,
      in cleft lip/palate-ectodermal dysplasia.
AB  - Cleft lip, with or without cleft palate (CL/P), is one of the most common birth
      defects, occurring in 0.4 to 2.0 per 1,000 infants born alive. Approximately 70%
      of CL/P cases are non-syndromic (MIM 119530), but CL/P also occurs in many single
      gene syndromes, each affecting a protein critical for orofacial development. Here
      we describe positional cloning of the gene responsible for an autosomal recessive
      CL/P-ectodermal dysplasia (ED) syndrome (CLPED1; previously ED4; ref. 2), which
      we identify as PVRL1, encoding nectin-1, an immunoglobulin (Ig)-related
      transmembrane cell-cell adhesion molecule that is part of the NAP cell adhesion
      system. Nectin-1 is also the principal cell surface receptor for alpha
      herpesviruses (HveC; ref. 7), and the high frequency of CLPED1 on Margarita
      Island in the Caribbean Sea might result from resistance of heterozygotes to
      infection by these viruses.

PMID- 10932189
TI  - Control of neurulation by the nucleosome assembly protein-1-like 2.
AB  - Neurulation is a complex process of histogenesis involving the precise temporal
      and spatial organization of gene expression. Genes influencing neurulation
      include proneural genes determining primary cell fate, neurogenic genes involved
      in lateral inhibition pathways and genes controlling the frequency of mitotic
      events. This is reflected in the aetiology and genetics of human and mouse neural
      tube defects, which are of both multifactorial and multigenic origin. The X
      linked gene Nap1l2, specifically expressed in neurons, encodes a protein that is
      highly similar to the nucleosome assembly (NAP) and SET proteins. We inactivated
      Nap1l2 in mice by gene targeting, leading to embryonic lethality from mid
      gestation onwards. Surviving mutant chimaeric embryos showed extensive surface
      ectoderm defects as well as the presence of open neural tubes and exposed brains
      similar to those observed in human spina bifida and anencephaly. These defects
      correlated with an overproduction of neuronal precursor cells. Protein expression
      studies showed that the Nap1l2 protein binds to condensing chromatin during S
      phase and in apoptotic cells, but remained cytoplasmic during G1 phase. Nap1l2
      therefore likely represents a class of tissue-specific factors interacting with
      chromatin to regulate neuronal cell proliferation.

PMID- 10932190
TI  - Molecular breeding of viruses.
AB  - Genetic recombination is a major force driving the evolution of many viruses.
      Recombination between two copackaged retroviral genomes may occur at rates as
      high as 40% per replication cycle. This enables genetic information to be
      shuffled rapidly, leading to recombinants with new patterns of mutations and
      phenotypes. The in vitro process of DNA shuffling (molecular breeding) mimics
      this mechanism on a vastly parallel and accelerated scale. Multiple homologous
      parental sequences are recombined in parallel, leading to a diverse library of
      complex recombinants from which desired improvements can be selected. Different
      proteins and enzymes have been improved using DNA shuffling. We report here the
      first application of molecular breeding to viruses. A single round of shuffling
      envelope sequences from six murine leukaemia viruses (MLV) followed by selection
      yielded a chimaeric clone with a completely new tropism for Chinese Hamster Ovary
      (CHOK1) cells. The composition and properties of the selected clone indicated
      that this particular permutation of parental sequences cannot be readily attained
      by natural retroviral recombination. This example demonstrates that molecular
      breeding can enhance the inherently high evolutionary potential of retroviruses
      to obtain desired phenotypes. It can be an effective tool, when information is
      limited, to optimize viruses for gene therapy and vaccine applications when
      multiple complex functions must be simultaneously balanced.

PMID- 10932191
TI  - A systematic, genome-wide, phenotype-driven mutagenesis programme for gene
      function studies in the mouse.
AB  - As the human genome project approaches completion, the challenge for mammalian
      geneticists is to develop approaches for the systematic determination of
      mammalian gene function. Mouse mutagenesis will be a key element of studies of
      gene function. Phenotype-driven approaches using the chemical mutagen
      ethylnitrosourea (ENU) represent a potentially efficient route for the generation
      of large numbers of mutant mice that can be screened for novel phenotypes. The
      advantage of this approach is that, in assessing gene function, no a priori
      assumptions are made about the genes involved in any pathway. Phenotype-driven
      mutagenesis is thus an effective method for the identification of novel genes and
      pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant
      mutations in the mouse. We generated and screened over 26,000 mice, and recovered
      some 500 new mouse mutants. Our work, along with the programme reported in the
      accompanying paper, has led to a substantial increase in the mouse mutant
      resource and represents a first step towards systematic studies of gene function
      in mammalian genetics.

PMID- 10932192
TI  - Genome-wide, large-scale production of mutant mice by ENU mutagenesis.
AB  - In the post-genome era, the mouse will have a major role as a model system for
      functional genome analysis. This requires a large number of mutants similar to
      the collections available from other model organisms such as Drosophila
      melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome
      wide, mutagenesis screen in mice. As part of the German Human Genome Project, we
      have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a
      limited screen for recessive mutations. In screening over 14,000 mice for a large
      number of clinically relevant parameters, we recovered 182 mouse mutants for a
      variety of phenotypes. In addition, 247 variant mouse mutants are currently in
      genetic confirmation testing and will result in additional new mutant lines. This
      mutagenesis screen, along with the screen described in the accompanying paper,
      leads to a significant increase in the number of mouse models available to the
      scientific community. Our mutant lines are freely accessible to non-commercial
      users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html).

PMID- 10932193
TI  - Spermiogenesis and exchange of basic nuclear proteins are impaired in male germ
      cells lacking Camk4.
AB  - Ca2+/calmodulin-dependent protein kinase IV (Camk4; also known as CaMKIV), a
      multifunctional serine/threonine protein kinase with limited tissue distribution,
      has been implicated in transcriptional regulation in lymphocytes, neurons and
      male germ cells. In the mouse testis, however, Camk4 is expressed in spermatids
      and associated with chromatin and nuclear matrix. Elongating spermatids are not
      transcriptionally active, raising the possibility that Camk4 has a novel function
      in male germ cells. To investigate the role of Camk4 in spermatogenesis, we have
      generated mice with a targeted deletion of the gene Camk4. Male Camk4-/- mice are
      infertile with impairment of spermiogenesis in late elongating spermatids. The
      sequential deposition of sperm basic nuclear proteins on chromatin is disrupted,
      with a specific loss of protamine-2 and prolonged retention of transition protein
      2 (Tnp2) in step-15 spermatids. Protamine-2 is phosphorylated by Camk4 in vitro,
      implicating a connection between Camk4 signalling and the exchange of basic
      nuclear proteins in mammalian male germ cells. Defects in protamine-2 have been
      identified in sperm of infertile men, suggesting that our results may have
      clinical implications for the understanding of human male infertility.

PMID- 10932194
TI  - Insertion of Inhbb into the Inhba locus rescues the Inhba-null phenotype and
      reveals new activin functions.
AB  - The activins (dimers of betaA or betaB subunits, encoded by the genes Inhba and
      Inhbb, respectively) are TGF-beta superfamily members that have roles in
      reproduction and development. Whereas mice homozygous for the Inhba-null allele
      demonstrate disruption of whisker, palate and tooth development, leading to
      neonatal lethality, homozygous Inhbb-null mice are viable, fertile and have eye
      defects. To determine if these phenotypes were due to spatiotemporal expression
      differences of the ligands or disruption of specific ligand-receptor
      interactions, we replaced the region of Inhba encoding the mature protein with
      Inhbb, creating the allele Inhbatm2Zuk (hereafter designated InhbaBK). Although
      the craniofacial phenotypes of the Inhba-null mutation were rescued by the
      InhbaBK allele, somatic, testicular, genital and hair growth were grossly
      affected and influenced by the dosage and bioactivity of the allele. Thus,
      functional compensation within the TGF-beta superfamily can occur if the
      replacement gene is expressed appropriately. The novel phenotypes in these mice
      further illustrate the usefulness of insertion strategies for defining protein
      function.

PMID- 10932195
TI  - Efficient and accurate replication in the presence of 7,8-dihydro-8-oxoguanine by
      DNA polymerase eta.
AB  - Oxidative damage to DNA has been proposed to have a role in cancer and ageing.
      Oxygen-free radicals formed during normal aerobic cellular metabolism attack
      bases in DNA, and 7, 8-dihydro-8-oxoguanine (8-oxoG) is one of the adducts
      formed. Eukaryotic replicative DNA polymerases replicate DNA containing 8-oxoG by
      inserting an adenine opposite the lesion; consequently, 8-oxoG is highly
      mutagenic and causes G:C to T:A transversions. Genetic studies in yeast have
      indicated a role for mismatch repair in minimizing the incidence of these
      mutations. In Saccharomyces cerevisiae, deletion of OGG1, encoding a DNA
      glycosylase that functions in the removal of 8-oxoG when paired with C, causes an
      increase in the rate of G:C to T:A transversions. The ogg1Delta msh2Delta double
      mutant displays a higher rate of CAN1S to can1r forward mutations than the
      ogg1Delta or msh2Delta single mutants, and this enhanced mutagenesis is primarily
      due to G:C to T:A transversions. The gene RAD30 of S. cerevisiae encodes a DNA
      polymerase, Poleta, that efficiently replicates DNA containing a cis-syn thymine
      thymine (T-T) dimer by inserting two adenines across from the dimer. In humans,
      mutations in the yeast RAD30 counterpart, POLH, cause the variant form of
      xeroderma pigmentosum (XP-V), and XP-V individuals suffer from a high incidence
      of sunlight-induced skin cancers. Here we show that yeast and human POLeta
      replicate DNA containing 8-oxoG efficiently and accurately by inserting a
      cytosine across from the lesion and by proficiently extending from this base
      pair. Consistent with these biochemical studies, a synergistic increase in the
      rate of spontaneous mutations occurs in the absence of POLeta in the yeast
      ogg1Delta mutant. Our results suggest an additional role for Poleta in the
      prevention of internal cancers in humans that would otherwise result from the
      mutagenic replication of 8-oxoG in DNA.

PMID- 10932196
TI  - Mutational hot spot within a new RPGR exon in X-linked retinitis pigmentosa.
AB  - The gene RPGR was previously identified in the RP3 region of Xp21.1 and shown to
      be mutated in 10-20% of patients with the progressive retinal degeneration X
      linked retinitis pigmentosa (XLRP). The mutations predominantly affected a domain
      homologous to RCC1, a guanine nucleotide exchange factor for the small GTPase
      Ran, although they were present in fewer than the 70-75% of XLRP patients
      predicted from linkage studies. Mutations in the RP2 locus at Xp11.3 were found
      in a further 10-20% of XLRP patients, as predicted from linkage studies. Because
      the mutations in the remainder of the XLRP patients may reside in undiscovered
      exons of RPGR, we sequenced a 172-kb region containing the entire gene. Analysis
      of the sequence disclosed a new 3' terminal exon that was mutated in 60% of XLRP
      patients examined. This exon encodes 567 amino acids, with a repetitive domain
      rich in glutamic acid residues. The sequence is conserved in the mouse, bovine
      and Fugu rubripes genes. It is preferentially expressed in mouse and bovine
      retina, further supporting its importance for retinal function. Our results
      suggest that mutations in RPGR are the only cause of RP3 type XLRP and account
      for the disease in over 70% of XLRP patients and an estimated 11% of all
      retinitis pigmentosa patients.

PMID- 10932197
TI  - Missed opportunities in Durban.

PMID- 10932199
TI  - "Catching heart disease": antigenic mimicry and bacterial infections.

PMID- 10932200
TI  - South African government continues policy of inactivity.

PMID- 10932198
TI  - Cellular prion protein is expressed in the human enteric nervous system.

PMID- 10932201
TI  - HIV vaccine trials planned for Africa.

PMID- 10932202
TI  - NIAID funds new groups to develop HIV vaccines.

PMID- 10932203
TI  - ellipsisand AHA announces support for the technique

PMID- 10932205
TI  - Wellcome extension to UK science museum

PMID- 10932206
TI  - GAO reports on CFS funding controversy.

PMID- 10932204
TI  - European ethicists discuss stem cell research...

PMID- 10932208
TI  - NIH expands graduate student training programs

PMID- 10932209
TI  - Spanish oncology center under threat

PMID- 10932207
TI  - Australian academic research buys into Celera.

PMID- 10932210
TI  - Telomere dynamics in cancer progression and prevention: fundamental differences
      in human and mouse telomere biology.
AB  - Cells from the telomerase knockout mouse immortalize with an approximately ten
      million-fold greater frequency than human cells. In this commentary, Wright and
      Shay discuss the implications of this difference between mice and men and its
      relationship to cancer.

PMID- 10932211
TI  - Mice without telomerase: what can they teach us about human cancer?
AB  - Unicellular organisms, human cells and mice have provided insights into the
      processes of senescence, crisis, genomic instability and cancer in humans. Here,
      Artandi and DePinho discuss how studies in mice have uncovered a complex
      interplay between the ARF-p53 pathway, genomic instability due to telomere
      dysfunction, and the suppression or promotion of cancer.

PMID- 10932212
TI  - The shape of the heart

PMID- 10932213
TI  - The methuselah gene: A science fiction adventure thriller

PMID- 10932214
TI  - Will radioiodine be useful in treatment of breast cancer?

PMID- 10932215
TI  - From parathyroid to thymus, via glial cells.

PMID- 10932216
TI  - Gene therapy scores against cancer.

PMID- 10932217
TI  - Human cytomegalovirus - no longer just a DNA virus.

PMID- 10932218
TI  - Lost in the FOG.

PMID- 10932219
TI  - A B-cell activator in Chagas disease.

PMID- 10932220
TI  - A rare find - cells that improve bone marrow transplantation.

PMID- 10932222
TI  - Research news

PMID- 10932221
TI  - Exposing tumor cells to killer cell attack.

PMID- 10932223
TI  - The mammary gland iodide transporter is expressed during lactation and in breast
      cancer.
AB  - The sodium/iodide symporter mediates active iodide transport in both healthy and
      cancerous thyroid tissue. By exploiting this activity, radioiodide has been used
      for decades with considerable success in the detection and treatment of thyroid
      cancer. Here we show that a specialized form of the sodium/iodide symporter in
      the mammary gland mediates active iodide transport in healthy lactating (but not
      in nonlactating) mammary gland and in mammary tumors. In addition to
      characterizing the hormonal regulation of the mammary gland sodium/iodide
      symporter, we demonstrate by scintigraphy that mammary adenocarcinomas in
      transgenic mice bearing Ras or Neu oncogenes actively accumulate iodide by this
      symporter in vivo. Moreover, more than 80% of the human breast cancer samples we
      analyzed by immunohistochemistry expressed the symporter, compared with none of
      the normal (nonlactating) samples from reductive mammoplasties. These results
      indicate that the mammary gland sodium/iodide symporter may be an essential
      breast cancer marker and that radioiodide should be studied as a possible option
      in the diagnosis and treatment of breast cancer.

PMID- 10932224
TI  - a controlled trial of intratumoral ONYX-015, a selectively-replicating
      adenovirus, in combination with cisplatin and 5-fluorouracil in patients with
      recurrent head and neck cancer.
AB  - ONYX-015 is an adenovirus with the E1B 55-kDa gene deleted, engineered to
      selectively replicate in and lyse p53-deficient cancer cells while sparing normal
      cells. Although ONYX-015 and chemotherapy have demonstrated anti-tumoral activity
      in patients with recurrent head and neck cancer, disease recurs rapidly with
      either therapy alone. We undertook a phase II trial of a combination of
      intratumoral ONYX-015 injection with cisplatin and 5-fluorouracil in patients
      with recurrent squamous cell cancer of the head and neck. There were substantial
      objective responses, including a high proportion of complete responses. By 6
      months, none of the responding tumors had progressed, whereas all non-injected
      tumors treated with chemotherapy alone had progressed. The toxic effects that
      occurred were acceptable. Tumor biopsies obtained after treatment showed tumor
      selective viral replication and necrosis induction.

PMID- 10932225
TI  - Identification of the Ebola virus glycoprotein as the main viral determinant of
      vascular cell cytotoxicity and injury.
AB  - Here we defined the main viral determinant of Ebola virus pathogenicity;
      synthesis of the virion glycoprotein (GP) of Ebola virus Zaire induced cytotoxic
      effects in human endothelial cells in vitro and in vivo. This effect mapped to a
      serine-threonine-rich, mucin-like domain of this type I transmembrane
      glycoprotein, one of seven gene products of the virus. Gene transfer of GP into
      explanted human or porcine blood vessels caused massive endothelial cell loss
      within 48 hours that led to a substantial increase in vascular permeability.
      Deletion of the mucin-like region of GP abolished these effects without affecting
      protein expression or function. GP derived from the Reston strain of virus, which
      causes disease in nonhuman primates but not in man, did not disrupt the
      vasculature of human blood vessels. In contrast, the Zaire GP induced endothelial
      cell disruption and cytotoxicity in both nonhuman primate and human blood
      vessels, and the mucin domain was required for this effect. These findings
      indicate that GP, through its mucin domain, is the viral determinant of Ebola
      pathogenicity and likely contributes to hemorrhage during infection.

PMID- 10932226
TI  - A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase.
AB  - Lymphocyte polyclonal activation is a generalized mechanism of immune evasion
      among pathogens. In a mouse model of Trypanosoma cruzi infection (American
      trypanosomiasis), reduced levels of polyclonal lymphocyte responses correlate
      with resistance to infection and cardiopathy. We report here the characterization
      of a parasite protein with B-cell mitogenic properties in culture supernatants of
      infective forms, the cloning of the corresponding gene and the analysis of the
      biological properties of its product. We characterized the protein as a co-factor
      independent proline racemase, and show that its expression as a cytoplasmic
      and/or membrane-associated protein is life-stage specific. Inhibition studies
      indicate that availability of the racemase active site is necessary for mitogenic
      activity. This is the first report to our knowledge of a eukaryotic amino acid
      racemase gene. Our findings have potential consequences for the development of
      new immune therapies and drug design against pathogens.

PMID- 10932227
TI  - Import of host delta-aminolevulinate dehydratase into the malarial parasite:
      identification of a new drug target.
AB  - The parasite Plasmodium berghei imports the enzyme delta-aminolevulinate
      dehydratase (ALAD), and perhaps the subsequent enzymes of the pathway from the
      host red blood cell to sustain heme synthesis. Here we have studied the mechanism
      of this import. A 65-kDa protein on the P. berghei membrane specifically bound to
      mouse red blood cell ALAD, and a 93-amino-acid fragment (ALAD-DeltaNC) of the
      host erythrocyte ALAD was able to compete with the full-length enzyme for binding
      to the P. berghei membrane. ALAD-DeltaNC was taken up by the infected red blood
      cell when added to a culture of P. falciparum and this led to a substantial
      decrease in ALAD protein and enzyme activity and, subsequently, heme synthesis in
      the parasite, resulting in its death.

PMID- 10932228
TI  - Characterization of a newly discovered T-cell receptor beta-chain heterodimer
      expressed on a CD8+ bone marrow subpopulation that promotes allogeneic stem cell
      engraftment.
AB  - The facilitating cell is a rare CD8+ bone marrow subpopulation that can enhance
      allogeneic hematopoietic stem cell engraftment across complete major
      histocompatibility complex barriers without inducing acute graft-versus-host
      disease. Here we describe a CD3epsilon-associated complex on the facilitating
      cell surface that consists of the T-cell receptor beta-chain disulfide-linked to
      a previously unknown 33-kilodalton glycoprotein. Provisionally called FCp33, this
      glycoprotein does not represent any of the known protein chains or surrogates
      associated with CD3-T-cell receptor beta. Expression of this CD3-T-cell receptor
      beta-FCp33 complex directly correlates with the facilitating cell's functional
      ability to enhance allogeneic stem cell engraftment in vivo.

PMID- 10932229
TI  - Increased sensitivity to the stimulant effects of morphine conferred by anti
      adhesive glycoprotein SPARC in amygdala.
AB  - Repeated administration of morphine substantially increases its locomotor
      enhancing activity, a phenomenon termed locomotor sensitization. Here we show
      that secreted protein acidic and rich in cysteine (SPARC), an anti-adhesive
      glycoprotein present in the basolateral amygdala, contributes to the
      establishment of locomotor sensitization. The morphine-induced increase in SPARC
      levels in the basolateral amygdala persisted after morphine withdrawal and
      coincided with the duration of locomotor sensitization. Moreover, a single
      injection of morphine after SPARC infusion into the basolateral amygdala of
      previously uninjected mice substantially enhanced locomotor activity. Thus, SPARC
      may be an important element for establishing locomotor sensitization to morphine.

PMID- 10932230
TI  - Peripherally administered antibodies against amyloid beta-peptide enter the
      central nervous system and reduce pathology in a mouse model of Alzheimer
      disease.
AB  - One hallmark of Alzheimer disease is the accumulation of amyloid beta-peptide in
      the brain and its deposition as plaques. Mice transgenic for an amyloid beta
      precursor protein (APP) mini-gene driven by a platelet-derived (PD) growth factor
      promoter (PDAPP mice), which overexpress one of the disease-linked mutant forms
      of the human amyloid precursor protein, show many of the pathological features of
      Alzheimer disease, including extensive deposition of extracellular amyloid
      plaques, astrocytosis and neuritic dystrophy. Active immunization of PDAPP mice
      with human amyloid beta-peptide reduces plaque burden and its associated
      pathologies. Several hypotheses have been proposed regarding the mechanism of
      this response. Here we report that peripheral administration of antibodies
      against amyloid beta-peptide, was sufficient to reduce amyloid burden. Despite
      their relatively modest serum levels, the passively administered antibodies were
      able to enter the central nervous system, decorate plaques and induce clearance
      of preexisting amyloid. When examined in an ex vivo assay with sections of PDAPP
      or Alzheimer disease brain tissue, antibodies against amyloid beta-peptide
      triggered microglial cells to clear plaques through Fc receptor-mediated
      phagocytosis and subsequent peptide degradation. These results indicate that
      antibodies can cross the blood-brain barrier to act directly in the central
      nervous system and should be considered as a therapeutic approach for the
      treatment of Alzheimer disease and other neurological disorders.

PMID- 10932231
TI  - Fas engagement accelerates liver regeneration after partial hepatectomy.
AB  - Fas (CD95) is a receptor involved in induction of apoptotic cell death of Fas
      bearing cells, including hepatocytes and T cells. Injection of Fas-specific
      antibodies into mice leads to fulminant hepatic failure and death. Fas also
      transduces growth-promoting signals in proliferating T cells, fibroblasts and
      some tumor cells. Here we show that partial hepatectomy, which triggers the
      immediate onset of liver regeneration, protected mice against the lethal effects
      of Fas-specific antibodies and prevented hepatocyte apoptosis in response to Fas
      engagement in vivo. Furthermore, Fas engagement accelerated liver regeneration
      after partial hepatectomy. Liver regeneration kinetics were delayed in mutant
      mice with decreased cell surface Fas expression (lpr mice). In contrast,
      regeneration was not delayed in lpr-cg mutant mice, which have a Fas mutation
      that prevents Fas-induced death but not Fas-dependent proliferative stimulation.
      Our results indicate that Fas engagement on cells in regenerating or healing
      tissues may promote cell growth.

PMID- 10932233
TI  - Fetal immunization by a DNA vaccine delivered into the oral cavity.
AB  - Infectious diseases are the main cause of neonatal morbidity and mortality in
      humans. The World Health Organization estimated that in 1995 approximately 8
      million infants died within the first year of life from infectious diseases,
      including 5 million during the first week of life. Some of the salient pathogens
      involved include herpes simplex virus, human immunodeficiency virus, hepatitis B
      virus, human cytomegalovirus, group B streptococcus, hemophilus and chlamydia.
      Infection with these pathogens usually occurs at the end of pregnancy, during
      birth or by breastfeeding. To reduce the risk of disease transmission, caesarian
      sections, prophylactic treatment with antibiotics or maternal antiviral therapy
      during the last trimester are used where available, together with improved
      neonatal care. None of these approaches, however, completely eliminates the risk
      of neonatal infection. Therefore, active or passive immunization of the fetus
      might represent an effective approach to reduce the high risk of neonatal
      diseases. Here, we demonstrate that a single immunization with a DNA vaccine
      delivered into the amniotic fluid in the oral cavity induces high serum antibody
      titers and a cell-mediated immune response, combined with induction of local
      immunity in the oral cavities of fetal lambs.

PMID- 10932232
TI  - Targeted disruption of the glucose transporter 4 selectively in muscle causes
      insulin resistance and glucose intolerance.
AB  - The prevalence of type 2 diabetes mellitus is growing worldwide. By the year
      2020, 250 million people will be afflicted. Most forms of type 2 diabetes are
      polygenic with complex inheritance patterns, and penetrance is strongly
      influenced by environmental factors. The specific genes involved are not yet
      known, but impaired glucose uptake in skeletal muscle is an early, genetically
      determined defect that is present in non-diabetic relatives of diabetic subjects.
      The rate-limiting step in muscle glucose use is the transmembrane transport of
      glucose mediated by glucose transporter (GLUT) 4 (ref. 4), which is expressed
      mainly in skeletal muscle, heart and adipose tissue. GLUT4 mediates glucose
      transport stimulated by insulin and contraction/exercise. The importance of GLUT4
      and glucose uptake in muscle, however, was challenged by two recent observations.
      Whereas heterozygous GLUT4 knockout mice show moderate glucose intolerance,
      homozygous whole-body GLUT4 knockout (GLUT4-null) mice have only mild
      perturbations in glucose homeostasis and have growth retardation, depletion of
      fat stores, cardiac hypertrophy and failure, and a shortened life span. Moreover,
      muscle-specific inactivation of the insulin receptor results in minimal, if any,
      change in glucose tolerance. To determine the importance of glucose uptake into
      muscle for glucose homeostasis, we disrupted GLUT4 selectively in mouse muscles.
      A profound reduction in basal glucose transport and near-absence of stimulation
      by insulin or contraction resulted. These mice showed severe insulin resistance
      and glucose intolerance from an early age. Thus, GLUT4-mediated glucose transport
      in muscle is essential to the maintenance of normal glucose homeostasis.

PMID- 10932235
TI  - On the market

PMID- 10932234
TI  - Quantification of target gene expression by imaging reporter gene expression in
      living animals.

PMID- 10932237
TI  - Free access?

PMID- 10932238
TI  - Converging on proline: the mechanism of WW domain peptide recognition.

PMID- 10932239
TI  - From crystal clear ligand binding to designer I domains.
AB  - A long awaited crystal structure of an integrin I domain in complex with a
      peptide derived from collagen has revealed the ligand-bound conformation of this
      domain and suggests a mechanism for allosteric control of integrin function by
      ligand binding. Also, a computational protein design approach has allowed the
      creation of stable, high affinity forms of the I domain for the first time.

PMID- 10932240
TI  - Intimate details of the most poisonous poison.
AB  - Crystal structures of type B botulinum neurotoxin, determined under conditions
      relevant to the extracellular binding and intracellular substrate cleavage steps
      of its toxic action, reveal that minimal structural changes occur upon binding a
      ganglioside or after substrate cleavage. The unique structure of this toxin
      provides information for developing preventive measures against botulism.

PMID- 10932241
TI  - Survivin structure: crystal unclear.
AB  - The recent X-ray structures of the anti-apoptotic protein survivin reveal two
      different dimeric interfaces. More experiments are needed to determine the
      biologically relevant dimer interface and to probe survivin function on the basis
      of its structure.

PMID- 10932242
TI  - Picture story. Restricted movement.

PMID- 10932243
TI  - Early ribbon drawings of proteins.

PMID- 10932244
TI  - A tale of two components: a novel kinase and a regulatory switch.
AB  - Histidine protein kinases and response regulators form the basis of
      phosphotransfer signal transduction pathways. Commonly referred to as two
      component systems, these modular and adaptable signaling schemes are prevalent in
      prokaryotes. Structures of the core domains of histidine kinases reveal a protein
      kinase fold different from that of the Ser/Thr/Tyr protein kinase family, but
      similar to that of other ATP binding domains. Recent structure determinations of
      phosphorylated response regulator domains indicate a conserved mechanism for the
      propagated conformational change that accompanies phosphorylation of an active
      site Asp residue. The altered molecular surface promotes specific protein-protein
      interactions that mediate the downstream response.

PMID- 10932245
TI  - Structure of a WW domain containing fragment of dystrophin in complex with beta
      dystroglycan.
AB  - Dystrophin and beta-dystroglycan are components of the dystrophin-glycoprotein
      complex (DGC), a multimolecular assembly that spans the cell membrane and links
      the actin cytoskeleton to the extracellular basal lamina. Defects in the
      dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C
      terminal region of dystrophin binds the cytoplasmic tail of beta-dystroglycan, in
      part through the interaction of its WW domain with a proline-rich motif in the
      tail of beta-dystroglycan. Here we report the crystal structure of this portion
      of dystrophin in complex with the proline-rich binding site in beta-dystroglycan.
      The structure shows that the dystrophin WW domain is embedded in an adjacent
      helical region that contains two EF-hand-like domains. The beta-dystroglycan
      peptide binds a composite surface formed by the WW domain and one of these EF
      hands. Additionally, the structure reveals striking similarities in the
      mechanisms of proline recognition employed by WW domains and SH3 domains.

PMID- 10932246
TI  - Structural basis for phosphoserine-proline recognition by group IV WW domains.
AB  - Pin1 contains an N-terminal WW domain and a C-terminal peptidyl-prolyl cis-trans
      isomerase (PPIase) domain connected by a flexible linker. To address the
      energetic and structural basis for WW domain recognition of phosphoserine
      (P.Ser)/phosphothreonine (P. Thr)- proline containing proteins, we report the
      energetic and structural analysis of a Pin1-phosphopeptide complex. The X-ray
      crystal structure of Pin1 bound to a doubly phosphorylated peptide (Tyr-P.Ser-Pro
      Thr-P.Ser-Pro-Ser) representing a heptad repeat of the RNA polymerase II large
      subunit's C-terminal domain (CTD), reveals the residues involved in the
      recognition of a single P.Ser side chain, the rings of two prolines, and the
      backbone of the CTD peptide. The side chains of neighboring Arg and Ser residues
      along with a backbone amide contribute to recognition of P.Ser. The lack of
      widespread conservation of the Arg and Ser residues responsible for P.Ser
      recognition in the WW domain family suggests that only a subset of WW domains can
      bind P.Ser-Pro in a similar fashion to that of Pin1.

PMID- 10932247
TI  - Probing protein-protein interactions in real time.
AB  - We have used a prototype small cantilever atomic force microscope to observe, in
      real time, the interactions between individual protein molecules. In particular,
      we have observed individual molecules of the chaperonin protein GroES binding to
      and then dissociating from individual GroEL proteins, which were immobilized on a
      mica support. This work suggests that the small cantilever atomic force
      microscope is a useful tool for studying protein dynamics at the single molecule
      level.

PMID- 10932248
TI  - Structure of the DNA binding domain of E. coli SSB bound to ssDNA.
AB  - The structure of the homotetrameric DNA binding domain of the single stranded DNA
      binding protein from Escherichia coli (Eco SSB) bound to two 35-mer single
      stranded DNAs was determined to a resolution of 2.8 A. This structure describes
      the vast network of interactions that results in the extensive wrapping of single
      stranded DNA around the SSB tetramer and suggests a structural basis for its
      various binding modes.

PMID- 10932249
TI  - Structural basis for the inhibition of porcine pepsin by Ascaris pepsin inhibitor
      3.
AB  - The three-dimensional structures of pepsin inhibitor-3 (PI-3) from Ascaris suum
      and of the complex between PI-3 and porcine pepsin at 1. 75 A and 2.45 A
      resolution, respectively, have revealed the mechanism of aspartic protease
      inhibition by this unique inhibitor. PI-3 has a new fold consisting of two
      domains, each comprising an antiparallel beta-sheet flanked by an alpha-helix. In
      the enzyme-inhibitor complex, the N-terminal beta-strand of PI-3 pairs with one
      strand of the 'active site flap' (residues 70-82) of pepsin, thus forming an
      eight-stranded beta-sheet that spans the two proteins. PI-3 has a novel mode of
      inhibition, using its N-terminal residues to occupy and therefore block the first
      three binding pockets in pepsin for substrate residues C-terminal to the scissile
      bond (S1'-S3'). The molecular structure of the pepsin-PI-3 complex suggests new
      avenues for the rational design of proteinaceous aspartic proteinase inhibitors.

PMID- 10932250
TI  - Structure of the heterodimeric complex between CAD domains of CAD and ICAD.
AB  - We present here the structure of the complex between the CAD domain of caspase
      activated deoxyribonuclease (CAD) and the CAD domain of its inhibitor (ICAD),
      determined by nuclear magnetic resonance spectroscopy. The two domains adopt a
      very similar fold, which consists of an alpha-helix and a beta-sheet, and are
      aligned side by side in the complex. Notably, the positive charges on the strand
      beta2 at one end of the beta-sheet of CAD and negative charges around the
      opposite end of the beta-sheet of ICAD are paired in the complex. Point mutations
      of the charged amino acids at this interface, on either CAD or ICAD, prevented
      formation of the functional CAD-ICAD complex. This implies that the interaction
      between the CAD domains of CAD and ICAD is an essential step in the correct
      folding of CAD in the complex.

PMID- 10932251
TI  - Structure of isocitrate lyase, a persistence factor of Mycobacterium
      tuberculosis.
AB  - Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium
      tuberculosis in mice by sustaining intracellular infection in inflammatory
      macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta
      oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential
      as a drug target against persistent infections, we solved its structure without
      ligand and in complex with two inhibitors. Covalent modification of an active
      site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a
      catalytic conformation with the active site completely inaccessible to solvent.
      The structure of a C191S mutant of the enzyme with the inhibitor 3
      nitropropionate provides further insight into the reaction mechanism.

PMID- 10932252
TI  - Critical role of beta-hairpin formation in protein G folding.
AB  - Comparison of the folding mechanisms of proteins with similar structures but very
      different sequences can provide fundamental insights into the determinants of
      protein folding mechanisms. Despite very little sequence similarity, the
      approximately 60 residue IgG binding domains of protein G and protein L both
      consist of a single helix packed against a four-stranded sheet formed by two
      symmetrically disposed beta-hairpins. We demonstrate that, as in the case of
      protein L, one of the two beta-turns of protein G is formed and the other
      disrupted in the folding transition state. Unlike protein L, however, in protein
      G it is the second beta-turn that is formed in the folding transition state
      ensemble. Substitution of an Asp residue by Ala in protein G that eliminates an
      i,i+2 side chain-main chain hydrogen bond in the second beta-turn slows the
      folding rate approximately 20-fold but has virtually no effect on the unfolding
      rate. Taken together with previous results, these findings suggest that the
      presence of an intact beta-turn in the folding transition state is a consequence
      of the overall topology of protein L and protein G, but the particular hairpin
      that is formed is determined by the detailed interatomic interactions that
      determine the free energies of formation of the isolated beta-hairpins.

PMID- 10932253
TI  - Computational design of an integrin I domain stabilized in the open high affinity
      conformation.
AB  - We have taken a computational approach to design mutations that stabilize a large
      protein domain of approximately 200 residues in two alternative conformations.
      Mutations in the hydrophobic core of the alphaMbeta2 integrin I domain were
      designed to stabilize the crystallographically defined open or closed conformers.
      When expressed on the cell surface as part of the intact heterodimeric receptor,
      binding of the designed open and closed I domains to the ligand iC3b, a form of
      the complement component C3, was either increased or decreased, respectively,
      compared to wild type. Moreover, when expressed in isolation from other integrin
      domains using an artificial transmembrane domain, designed open I domains were
      active in ligand binding, whereas designed closed and wild type I domains were
      inactive. Comparison to a human expert designed open mutant showed that the
      computationally designed mutants are far more active. Thus, computational design
      can be used to stabilize a molecule in a desired conformation, and conformational
      change in the I domain is physiologically relevant to regulation of ligand
      binding.

PMID- 10932254
TI  - Conservation of folding pathways in evolutionarily distant globin sequences.
AB  - To test the hypothesis that the folding pathways of evolutionarily related
      proteins with similar three-dimensional structures but widely different sequences
      should be similar, the folding pathway of apoleghemoglobin has been characterized
      using stopped-flow circular dichroism, heteronuclear NMR pulse labeling
      techniques and mass spectrometry. The pathway of folding was found to differ
      significantly from that of a protein of the same family, apomyoglobin, although
      both proteins appear to fold through helical burst phase intermediates. For
      leghemoglobin, the burst phase intermediate exhibits stable helical structure in
      the G and H helices, together with a small region in the center of the E helix.
      The A and B helices are not stabilized until later stages of the folding process.
      The structure of the burst phase folding intermediate thus differs from that of
      apomyoglobin, in which stable helical structure is formed in the A, B, G and H
      helix regions.

PMID- 10932255
TI  - Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at
      2.0 A resolution.
AB  - Botulinum neurotoxin serotype B is a zinc protease that disrupts neurotransmitter
      release by cleaving synaptobrevin-II (Sb2), one of three SNARE proteins involved
      in neuronal synaptic vesicle fusion. The three-dimensional crystal structure of
      the apo botulinum neurotoxin serotype B catalytic domain (BoNT/B-LC) has been
      determined to 2.2 A resolution, and the complex of cleaved Sb2 with the catalytic
      domain (Sb2-BoNT/B-LC) has been determined to 2.0 A resolution. A comparison of
      the holotoxin catalytic domain and the isolated BoNT/B-LC structure shows a
      rearrangement of three active site loops. This rearrangement exposes the BoNT/B
      active site. The Sb2-BoNT/B-LC structure illustrates two distinct binding
      regions, which explains the specificity of each botulinum neurotoxin for its
      synaptic vesicle protein. This observation provides an explanation for the
      proposed cooperativity between binding of full-length substrate and catalysis and
      suggest a mechanism of synaptobrevin proteolysis employed by the clostridial
      neurotoxins.

PMID- 10932256
TI  - Structural analysis of the catalytic and binding sites of Clostridium botulinum
      neurotoxin B.
AB  - Clostridium botulinum neurotoxins are among the most potent toxins to humans. The
      crystal structures of intact C. botulinum neurotoxin type B (BoNT/B) and its
      complex with sialyllactose, determined at 1. 8 and 2.6 A resolution,
      respectively, provide insight into its catalytic and binding sites. The position
      of the belt region in BoNT/B is different from that in BoNT/A; this observation
      presents interesting possibilities for designing specific inhibitors that could
      be used to block the activity of this neurotoxin. The structures of BoNT/B and
      its complex with sialyllactose provide a detailed description of the active site
      and a model for interactions between the toxin and its cell surface receptor. The
      latter may provide valuable information for recombinant vaccine development.

PMID- 10932258
TI  - Laparoscopy in Turkish bariatric surgery: initial experience.
AB  - BACKGROUND: The recent application of the laparoscopic method combines minimal
      invasiveness with reversibility, adjustability and shorter hospital stay. The
      first laparoscopic bariatric operation in Turkey was performed by us in 1998.
      METHODS: We report the results in 50 consecutive patients who underwent the
      laparoscopic application of SAGB between April 1998 and April 1999. The operation
      setting was the same as for the laparoscopic antireflux procedure. After a closed
      CO2 pneumoperitoneum (16-18 mmHg), in the first 20 cases five and in the
      remaining 30 cases four trocars were inserted. A 30 degrees laparoscope was
      placed on the line between the umbilicus and the xiphoid through a 10 mm trocar.
      We followed and respected the main steps of the operation as well. Pre and
      postoperative body weight (BW), body mass index (BMI) and percent excess weight
      (%EW) values were calculated and compared. RESULTS: Our early results were quite
      satisfactory and promising. After an average follow-up period of 1 year (range 6
      18 months), the 50 patients of our laparoscopic series showed a BW of 74 kg
      (range 56-112), a BMI of 29 (range 21-40), and an EW of 62% (range 22-86).
      CONCLUSION: With its lower morbidity rate, shorter hospital stay and better
      cosmetic results, the laparoscopic approach may be considered the first choice in
      bariatric surgery.

PMID- 10932257
TI  - Body composition and muscle constituents during weight loss: studies in obese
      patients following gastroplasty.
AB  - BACKGROUND: The influence of rapid and prolonged weight loss on body composition
      and muscle constituents in the obese patient is not well known. There are serious
      complications related to rapid and prolonged weight loss. It is of general
      interest to increase the understanding of the mechanisms and consequences of
      significant weight loss in man. METHODS: In 40 obese patients, the body
      composition and muscle constituents were studied before and during 1 year of
      weight loss following gastroplasty. The study was undertaken in two groups (A and
      B) of obese patients, comprising 32 women and eight men, body weight 82-175 kg
      and aged 24-49 years. Mean BMI in group A and B was 45 (W/H(2)) and 43 (W/H(2))
      respectively. Body composition was assessed by total body potassium measurements
      and muscle constituents were determined by analyses of muscle specimens obtained
      percutaneously. RESULTS: The preoperative body composition was found to be equal
      parts of lean body mass and body fat. Preoperatively, muscle constituents
      revealed a higher protein content per cell and a lower potassium concentration
      related to fat-free solids. The loss of 18-28% body fat and lean body mass
      occurred in equal proportions during the first 3 postoperative months of rapid
      weight loss, followed by a continuous decrease of body fat but not of lean body
      mass. The concentrations of proteins and potassium per muscle cell revealed a
      reduction during the period of rapid weight loss. The RNA/DNA ratio 1 year after
      surgery was still reduced, indicating a low protein synthesis rate. CONCLUSIONS:
      Preoperatively mean body fat accounted for 50% of the body weight in obese
      patients. Following weight loss, body fat, lean body mass and concentrations of
      proteins were reduced compared to preoperative values. After the period of rapid
      weight loss, with reduction of lean body mass and body fat in parallel, a
      progressive reduction of body fat was observed whereas the lean body mass did not
      decrease further. Protein synthesis rate was still low 12 months after surgery.

PMID- 10932259
TI  - A rare complication of adjustable gastric banding: Wernicke's encephalopathy.
AB  - BACKGROUND: Wernicke's encephalopathy is an uncommon complication seen after
      morbid obesity surgery. Neurological and cardiac symptoms can occur. Early and
      adequate replacement of thiamin is crucial. METHODS: A patient, who was operated
      by adjustable silicone gastric banding had severe vomiting 1 week after the
      operation. Physical examination showed no abnormalities except neurological signs
      consisting of ataxia, disorientation and diplopia. All radiological and
      biochemical parameters were in the normal range. RESULT: After replacement of
      vitamin B1 (thiamin) intravenously 20 mg twice daily, all the neurological signs
      regressed day by day. Oral thiamin pills have been continued. CONCLUSION:
      Wernicke's encephalopathy which occurs as a result of thiamin deficiency is a
      rare complication that has serious morbidity with rapidly progressing neurologic
      symptoms, and must be treated immediately. Surgeons who treat morbidly obese
      patients must follow the metabolic and nutritional status of the patient.

PMID- 10932260
TI  - Vision and insight in the search for gene mutations causing nonsyndromal mental
      deficiency.

PMID- 10932261
TI  - Can bioinformatics help trace the steps from gene mutation to disease?

PMID- 10932262
TI  - Using the electroretinogram to detect and monitor the retinal toxicity of
      anticonvulsants.

PMID- 10932263
TI  - A gene for nonsyndromic mental retardation maps to chromosome 3p25-pter.
AB  - OBJECTIVE: To establish genetic linkage between polymorphic microsatellite loci
      and a disease locus responsible for an autosomal recessive type of nonsyndromic
      mental retardation (MR). BACKGROUND: Although MR is the most common developmental
      disability in the United States, the etiologies of most nonsyndromic cases are
      not known. METHODS: A genealogic database provided information to reconstruct the
      relationships between 32 individuals from five nuclear families in a single
      pedigree with 10 affected individuals with nonsyndromic MR. To find a MR disease
      locus in this population, we performed a genome-wide search using genetic loci
      spaced at 10- to 20-cM intervals. Pairwise linkage analysis, multipoint linkage
      analysis, and haplotype reconstruction were used to localize the disease gene.
      RESULTS: Genetic linkage between a MR disease locus and locus D3S3050 on
      chromosome 3p25-pter was established with a Zmax = 9.18 at theta = 0.00. Fine
      mapping this region delimited a 13. 47-cM candidate interval defined by key
      recombinants at loci D3S3525 and D3S1304. Multipoint linkage analysis refined the
      critical region to a 6.71-cM interval flanked by loci D3S3525 and D3S1560.
      Evidence that a gene for MR resides in this location is supported by previous
      breakpoint deletion mapping studies performed in the chromosome 3p- syndrome.
      CONCLUSIONS: These results suggest that a gene on the subtelomeric region of
      chromosome 3p contributes to general intelligence. The genes for the cell
      adhesion L1-like molecule (CALL), the inositol triphosphate receptor (ITPR1), and
      the AD neuronal thread protein (AD7c-NTP) are leading positional candidates
      because of their role in brain development, neuronal signaling, and structure.

PMID- 10932264
TI  - Mutation spectrum and predicted function of laforin in Lafora's progressive
      myoclonus epilepsy.
AB  - BACKGROUND: Lafora's disease is a progressive myoclonus epilepsy with
      pathognomonic inclusions (polyglucosan bodies) caused by mutations in the EPM2A
      gene. EPM2A codes for laforin, a protein with unknown function. Mutations have
      been reported in the last three of the gene's exons. To date, the first exon has
      not been determined conclusively. It has been predicted based on genomic DNA
      sequence analysis including comparison with the mouse homologue. OBJECTIVES: 1)
      To detect new mutations in exon 1 and establish the role of this exon in Lafora's
      disease. 2) To generate hypotheses about the biological function of laforin based
      on bioinformatic analyses. METHODS: 1) PCR conditions and components were refined
      to allow amplification and sequencing of the first exon of EPM2A. 2) Extensive
      bioinformatic analyses of the primary structure of laforin were completed.
      RESULTS: 1) Seven new mutations were identified in the putative exon 1. 2)
      Laforin is predicted not to localize to the cell membrane or any of the
      organelles. It contains all components of the catalytic active site of the family
      of dual-specificity phosphatases. It contains a sequence predicted to encode a
      carbohydrate binding domain (coded by exon 1) and two putative glucohydrolase
      catalytic sites. CONCLUSIONS: The identification of mutations in exon 1 of EPM2A
      establishes its role in the pathogenesis of Lafora's disease. The presence of
      potential carbohydrate binding and cleaving domains suggest a role for laforin in
      the prevention of accumulation of polyglucosans in healthy neurons.

PMID- 10932265
TI  - Separating the retinal electrophysiologic effects of vigabatrin: treatment versus
      field loss.
AB  - OBJECTIVE: To separate the retinal electrophysiologic markers associated with
      vigabatrin-attributed visual field loss (VGB-VFL) from those associated with
      current vigabatrin therapy. METHODS: A nonrandomly selected cohort of 8 previous
      and 18 current vigabatrin users and a reference cohort of 8 never vigabatrin
      treated patients with epilepsy receiving other antiepilepsy drugs (AED) underwent
      electro-oculography (EOG), electroretinography (ERG), and automated static
      threshold perimetry. A cohort of 22 normal subjects underwent ERG. The validity
      of the retinal electrophysiologic variables to detect the presence and severity
      of VGB-VFL was assessed using receiver operator characteristic curves. RESULTS:
      Of 26 patients exposed to vigabatrin, 18 exhibited VGB-VFL. No patients receiving
      alternative AED showed this type of visual field abnormality. The presence and
      severity of VGB-VFL was significantly associated with the latency (implicit time)
      and amplitude of the ERG cone function. The amplitude of the cone flicker
      response was the strongest predictor of VGB-VFL and revealed a sensitivity of
      100% at a specificity of 75%. The EOG, the photopic and scotopic ERG, and the
      latency of the ERG second oscillatory potential (OP2) were not significantly
      related to the presence of VGB-VFL. Vigabatrin therapy was significantly
      associated with the photopic amplitude, the scotopic a-wave latency, and the
      latency of OP2. CONCLUSION: In patients who cannot perform reliable perimetry,
      the cone-specific ERG flicker amplitude provides the best screening method for
      detecting VGB-VFL.

PMID- 10932267
TI  - Access www.neurology.org now for full-text articles

PMID- 10932266
TI  - Abnormal vergence with upper brainstem infarcts: pseudoabducens palsy.
AB  - BACKGROUND: Infarcts of the rostral brainstem often cause vertical gaze palsies
      but may also produce inappropriate convergence that manifests as pseudoabducens
      palsy and convergence-retraction nystagmus (CRN). Although the substrate for
      vergence has been defined in the monkey as lying dorsal and lateral to the
      oculomotor nucleus, the human homologue is unknown. METHOD: - The authors
      reviewed the clinical features, ocular findings, and CT or MR lesions in seven
      patients with pseudoabducens palsy and "top-of-the-basilar" infarction. They
      reviewed the literature for infarcts causing pseudoabducens palsy or CRN with
      precise autopsy localization. The authors then mapped the location of the
      infarcts on anatomic templates. RESULTS: The smallest MR infarct produced an
      ipsilateral pseudoabducens palsy and CRN, and was located just rostral to the
      oculomotor nucleus, near the midbrain-diencephalic junction. Two patients with
      only contralateral pseudoabducens palsy had both subthalamic and thalamic
      infarction. Four patients with bilateral pseudoabducens palsy had larger infarcts
      involving the midbrain. All patients with pseudoabducens palsy had upgaze palsy.
      Two patients with CRN from the literature had small infarcts near the midbrain
      diencephalic junction at autopsy. CONCLUSIONS: Lesions near the midbrain
      diencephalic junction are important for the development of pseudoabducens palsy.
      Pseudoabducens palsy and CRN are probably both manifestations of abnormal
      vergence activity. Inhibitory descending pathways for convergence may pass
      through the thalamus and decussate in the subthalamic region.

PMID- 10932268
TI  - Transient increase in procollagen propeptides in the CSF after subarachnoid
      hemorrhage.
AB  - BACKGROUND: Meningeal fibrosis following subarachnoid hemorrhage (SAH) has been
      verified histologically in experimental animals and in human autopsy samples, but
      the clinical course of the intrathecal fibroproliferative reaction is unknown.
      The authors therefore studied time-related changes in the CSF concentrations of
      type I (PICP) and type III (PIIINP) procollagen propeptides in patients with
      recent SAH. METHOD: Fifty-two CSF samples were obtained from 39 patients with SAH
      treated surgically and eight samples from eight patients with SAH who were not
      surgically treated. The samples were analyzed for PICP and PIIINP by using
      radioimmunoassays. RESULTS: The authors found a time-dependent increase in PICP
      and PIIINP in the CSF of the patients with SAH. Two weeks after the hemorrhage,
      concentrations were four times higher in patients with SAH than the
      concentrations in the control subjects. Concentrations in patients with SAH then
      declined steadily, but remained slightly but significantly elevated even at 10
      weeks. PICP and PIIINP did not correlate with the age or sex of the patient or
      the amount of blood in the initial CT scan. Four patients developed late
      posthemorrhagic hydrocephalus; their PICP and PIIINP levels were higher than in
      matched patients with SAH without hydrocephalus. CONCLUSIONS: Time-dependent
      changes in CSF concentrations of PICP and PIIINP suggest a transient
      fibroproliferative reaction in the meninges after SAH. The considerable magnitude
      and extended time course of the changes make the measurement of PICP and PIIINP
      practicable for the diagnosis of a fibroproliferative state in patients with
      recent meningeal disease. Furthermore, the results suggest a role for meningeal
      fibrosis in the development of late posthemorrhagic hydrocephalus.

PMID- 10932269
TI  - Unilateral spatial neglect in AD: significance of line bisection performance.
AB  - BACKGROUND: Unilateral spatial neglect has been rarely reported in patients with
      AD, although they often have right and left asymmetry of temporoparietal
      dysfunction. OBJECTIVE: To investigate if patients with AD would show unilateral
      spatial neglect in the line bisection test, and to reveal the relationship
      between their neglect and the area of cerebral dysfunction. METHOD: Thirty-two
      patients with mild to moderate AD and 32 age-matched healthy control subjects
      underwent an extensive line bisection test. SPECT was also obtained for the
      patients. RESULTS: Rightward bisection errors exceeded the normal range in 25% of
      patients with AD. They exhibited greater rightward errors for the longer lines in
      the left hemispace than in the right hemispace, and with the right hand than with
      the left hand; this corresponds to the characteristics of neglect seen after
      right hemisphere lesions. All patients who bisected 200 mm lines with errors over
      10 mm showed disproportionate lowering of performance IQ and asymmetric right
      hemisphere hypoperfusion, especially in the temporoparietal region. Seventy-five
      percent of the patients performed normally in the center presentation but erred
      slightly toward the body midline in the right and left hemispaces. CONCLUSION:
      Left unilateral spatial neglect in mild to moderate AD may be rather common if
      tested with the line bisection test. Rightward errors over 10 mm suggest right
      temporoparietal dysfunction. In AD, three or more bisections of 200 mm lines in
      the center presentation are recommended for detection of neglect. Patients with
      AD but without neglect may have difficulty in shifting attention into the
      peripheral sector of the egocentric space.

PMID- 10932270
TI  - "Preclinical" AD revisited: neuropathology of cognitively normal older adults.
AB  - OBJECTIVE: To classify neuropathologic alterations in the brains of nondemented
      older adults using current sets of criteria for AD. BACKGROUND: AD
      neuropathologic alterations are found in the brains of some nondemented elderly
      subjects and suggest the possibility of presymptomatic AD. Three sets of
      guidelines have been developed to classify AD using senile plaques, neuritic
      plaques, and neurofibrillary tangles (NFT). METHODS: Neuropathologic changes in
      59 older adults followed longitudinally with a standard battery of mental status
      measures were investigated using Khachaturian, Consortium to Establish a Registry
      for Alzheimer's Disease (CERAD), and National Institute on Aging-Reagan Institute
      (NIA-RI) guidelines. AD neuropathologic markers were evaluated in neocortical and
      allocortical regions. Cases were categorized as neuropathologically "normal" or
      "AD-like" and compared for possible mental status differences. RESULTS: Between
      11 and 49% of cases met one or more of the three classifications of AD. With
      adjustments for multiple comparisons, only NFT in hippocampal CA1 region were
      associated with autopsy age, suggesting that this may represent a pathologic
      process associated with normal brain aging. Using the NIA-RI guidelines, subjects
      in the AD-like group performed less well on the immediate paragraph recall and
      word-list delayed recall than their counterparts who did not meet these
      guidelines. CONCLUSIONS: These data indicate that the prevalence of "preclinical"
      AD in our population is relatively low based on the NIA-RI classification.
      Although many subjects had AD-like changes based on CERAD and Khachaturian
      guidelines, they exhibited no differences in mental performance, suggesting that
      the aging brain may be able to withstand such structural changes without
      meaningful impact on mental functioning.

PMID- 10932271
TI  - Mapping the basal ganglia: fMRI evidence for somatotopic representation of face,
      hand, and foot.
AB  - OBJECTIVE: To noninvasively investigate the somatotopy of the basal ganglia in
      humans. METHODS: Functional MRI, 1.5-T, was performed on six normal right-handed
      volunteers during simple acoustically paced motor tasks involving the right hand,
      foot, and face. RESULTS: In a single-subject analysis, statistical parametric
      maps showed overlapping activation extending along the anteroposterior extent of
      the left lentiform nucleus (LLN) for the hand, foot, and face representations.
      Within the LLN, the centers of gravity of each body part, reflecting both the
      extent and gradient of activation, were all located in the retrocommissural
      portion of the putamen. Their spatial relationship followed a similar pattern
      across subjects-face was medial to toes and fingers, toes were dorsal and rostral
      to fingers. CONCLUSIONS: The somatotopic organization of hand, face, and foot
      representation in the human lentiform nucleus suggests a triangular pattern,
      rather than the linear pattern seen in primate studies. The overlap observed
      between the distinct body parts differs from the cortical sensorimotor
      representation, indicating a different organizational concept of the basal
      ganglia.

PMID- 10932272
TI  - Proximal myotonic myopathy: evidence for anticipation in families with linkage to
      chromosome 3q.
AB  - OBJECTIVE: To investigate anticipation in proximal myotonic myopathy (PROMM).
      BACKGROUND: PROMM is a recently described autosomal dominantly inherited disorder
      similar to but distinct from myotonic dystrophy (DM). DM belongs to the group of
      inherited disorders with anticipation caused by an unstable trinucleotide repeat
      expansion. In PROMM, no mutation has been identified, although PROMM has recently
      been mapped to a gene locus on chromosome 3q. METHODS: We investigated 10 German
      families with the PROMM phenotype and linkage to chromosome 3q. We based our
      analysis of anticipation on the age of disease onset. Anticipation was assumed if
      the offspring had first symptoms earlier in life than his or her affected parent.
      For statistical analysis Independence Estimating Equations (IEE) and a Monte
      Carlo bootstrap were used. RESULTS: In 27 affected living parent-offspring pairs
      from these 10 families, the mean difference of disease onset was 18.8 years with
      either statistical analysis (p < 10-14 and p < 10-15). The mean disease onset
      interval in years was greater in father-offspring as compared to the mother
      offspring pairs (p < 0.05; IEE). CONCLUSION: Our findings suggest the occurrence
      of anticipation in parent-offspring pairs from families with the PROMM phenotype
      and linkage to chromosome 3q. The different disease onset intervals in mother
      offspring and father-offspring pairs could indicate a mild parent-of-origin
      effect. These observations are compatible with the suggestion that PROMM, like
      DM, may be a trinucleotide repeat associated disorder. In contrast to DM,
      anticipation in PROMM is milder, a congenital form does not seem to occur, and
      fertility does not appear to be affected.

PMID- 10932273
TI  - Quality of life in ALS depends on factors other than strength and physical
      function.
AB  - OBJECTIVES: To study patients with ALS to determine the following: 1) the
      relationship between physical function and quality of life (QOL); 2) the
      instruments that best reflect patients' own ratings of QOL; and 3) whether
      spiritual/religious factors play a role in determining QOL. METHODS: The authors
      prospectively studied 96 patients with ALS using several instruments, including
      the McGill Quality of Life (MQOL) instrument, the Idler Index of Religiosity, the
      Sickness Impact Profile (SIP)/ALS-19, and several measures of strength and
      physical function. RESULTS: QOL as assessed by patients (MQOL single item score)
      did not correlate with measures of physical function and strength, but correlated
      with the total MQOL score (p < 0.0005), the psychological and existential
      subscores of MQOL (p < 0. 0005), the support subscore of MQOL (p = 0.001), and
      the total Idler score (p = 0.001). In contrast, correlations between SIP/ALS-19
      and these measures were not significant, although SIP/ALS-19 correlated with
      measures of physical function and strength. CONCLUSIONS: QOL, as assessed by the
      patient with ALS, does not correlate with measures of strength and physical
      function, but appears to depend on psychological and existential factors, and
      thus may be measured well by the MQOL scale. Spiritual factors and support
      systems appear to play roles as well. SIP/ALS-19 is a good measure of physical
      function, but not of overall QOL.

PMID- 10932274
TI  - Hereditary motor and sensory neuropathy with myelin folding and juvenile onset
      glaucoma.
AB  - OBJECTIVE: We describe three patients from a family with motor and sensory
      neuropathy accompanied by open-angle glaucoma. BACKGROUND: Autosomal recessive
      demyelinating hereditary motor and sensory neuropathies (HMSN) include different
      disorders. To our knowledge, autosomal recessive HMSN has not been associated
      with juvenile onset glaucoma. METHODS: Sural nerve pathology of the three
      patients were examined, and genetic analysis of the family was performed. RESULT:
      - The most prominent pathologic finding was a highly unusual myelin abnormality
      consisting of irregular redundant loops and folding of the myelin sheath. The
      family survey supports autosomal recessive inheritance. The molecular analysis
      failed to demonstrate either linkage of the disease to MPZ gene, PMP22 gene, Cx32
      gene, orEGR2 gene. Analysis did not establish linkage of the disease to the locus
      of CMT4A, 4B, and 4C genes. CONCLUSION: The present cases may represent a new
      type of HMSN accompanied by juvenile onset glaucoma.

PMID- 10932275
TI  - Immunoregulation and blocking antibodies induced by interferon beta treatment in
      MS.
AB  - OBJECTIVE: To examine the in vivo immunoregulatory properties of interferon beta
      1a (IFN beta-1a) on the T cell responses to myelin basic protein (MBP) and to
      evaluate the occurrence of the blocking antibodies characterized by the ability
      to reverse the effects of IFN beta on T cells in MS patients treated with IFN
      beta. METHODS: The precursor frequency of T cells recognizing MBP and control
      antigens was estimated in a microwell culture system. The cytokine profile of T
      cell lines was measured in ELISA. The binding antibodies were determined in ELISA
      and Western blot. Cytopathic test and the T cell functional assays were used to
      determine the blocking effects of the binding antibodies. RESULTS: Treatment with
      IFN beta resulted in a substantial reduction in the precursor frequency of MBP
      reactive T cells in MS patients. The cytokine profile of MBP-reactive T cells
      that sustained the treatment was altered toward an increased production of
      interleukin (IL)-10 and decreased production of tumor necrosis factor (TNF)alpha
      and IFN-gamma. The immunoregulatory properties of IFN beta on T cells could be
      blocked by the binding antibodies derived from a proportion of patients treated
      with IFN beta (4 of 64, 6.25%). The blocking antibodies also neutralized anti
      viral activity of IFN beta in cytopathic assays, corresponding to previously
      described neutralizing antibodies. CONCLUSIONS: Treatment with IFN beta alters
      the cytokine profile by enhancing the production of IL-10 and downregulating Th1
      cytokines, which may contribute to clinical benefit in MS. The treatment also
      induces blocking antibodies that impair the immunoregulatory properties of IFN
      beta in some individuals.

PMID- 10932276
TI  - Creutzfeldt-Jakob disease with a novel four extra-repeat insertional mutation in
      the PrP gene.
AB  - OBJECTIVE: To investigate the role of a short insertional mutation in the prion
      protein (PrP) gene (PRNP) in prion disease pathogenesis. BACKGROUND: The genetic
      forms of Creutzfeldt-Jakob disease (CJD) are associated with point or insertional
      mutations in PRNP. Whereas patients with five, six, seven, eight, and nine extra
      octapeptide repeats show an autosomal dominant pattern of inheritance and
      features of CJD, Gerstmann-Straussler-Scheinker disease, or atypical dementia,
      patients with one, two, or four extra repeats have typical CJD and lack a family
      history of neurologic disorder. METHODS: A genetic, neuropathologic, and
      biochemical study was carried out in a 65-year-old patient with clinical features
      of sporadic CJD. RESULTS: A novel four extra-repeat insertional mutation of PRNP
      was found in the patient and in his 59-year-old healthy sister. The patient
      showed spongiosis, nerve cell loss, and gliosis associated with diffuse PrP
      immunoreactivity in the cerebral cortex, subcortical gray structures, and
      cerebellum. A peculiar aspect was the presence of focal PrP deposits in the basal
      ganglia and hypothalamus, superimposed to diffuse PrP immunoreactivity. The
      biochemical analysis revealed that both mutant and wild-type PrP participated in
      the pathologic process, and that the protease-resistant core of the altered PrP
      isoforms was distinct from that observed in sporadic, acquired, and other genetic
      forms of CJD. CONCLUSION: These findings support the view that the four extra
      repeat insertion in PRNP is a pathogenic mutation with low penetrance rather than
      a benign polymorphism, and suggest that this mutation results in the formation of
      a distinct PrP conformer.

PMID- 10932277
TI  - Neuropsychological changes between "off" and "on" STN or GPi stimulation in
      Parkinson's disease.
AB  - BACKGROUND: In a previous study on a consecutive series of 62 patients with PD,
      the authors showed that bilateral subthalamic or pallidal continuous high
      frequency deep brain stimulation (DBS) affects neither memory nor executive
      functions 3 to 6 months after surgery. OBJECTIVE: To investigate the specific
      effects of DBS by comparing the performance of patients with the stimulator
      turned "on" and "off." METHODS: The performance of 56 patients on clinical tests
      of executive function was compared after 3 and 12 months of DBS of the
      subthalamic nucleus (STN; n = 48) or the internal globus pallidus (GPi; n = 8)
      with the stimulator "on" or "off." Global intellectual efficiency, verbal
      learning, and mood were also evaluated with the stimulator "on." The performance
      of another group of 20 patients was compared after 6 months of DBS of the STN (n
      = 15) or the GPi (n = 5) with the stimulator "on" or "off" on more experimental
      tests recently shown to be more sensitive to l-dopa therapy. RESULTS: When the
      stimulator was "on," STN patients showed a mild but significant improvement in
      psychomotor speed and working memory. In comparison with the presurgical state,
      STN patients had no cognitive deficit at 12 months, except for lexical fluency.
      There was no differential effect of STN or GPi stimulation. CONCLUSIONS: 1) The
      specific effect of DBS seems to mimic the action of l-dopa treatment in the
      cognitive as in the motor domain; 2) the surgery associated with DBS does not
      appear to affect the cognitive performance of patients with PD 12 months later,
      except for a mild deficit in lexical fluency.

PMID- 10932279
TI  - Activate your online subscription

PMID- 10932278
TI  - Hypoglycemia-induced cerebellar dysfunction and quantitative positron emission
      tomography study.
AB  - OBJECTIVE: To describe an unusual case of hypoglycemia-induced bilateral
      cerebellar dysfunction. BACKGROUND: The cerebellum is known to be resistant to
      hypoglycemia, and selective cerebellar dysfunction caused by hypoglycemia has not
      been reported. Previous studies showed that the ratio between the rate constants
      for glucose uptake and phosphorylation (K1 and k3) is reversed in the cerebellum
      compared with the cerebral cortex; higher K1 in the cerebellum and higher k3 in
      the cerebral cortex. METHODS: Quantitative dynamic PET scanning with labeled
      fluorodeoxyglucose (18F-FDG) was performed to prove altered glucose kinetics in
      the cerebellum of a patient who presented with episodic cerebellar dysfunction
      associated with hypoglycemia. Four control subjects underwent the same study.
      RESULTS: The ratio between K1 and k3 was not reversed in the cerebellum of our
      patient (K1 = 0.082, k3 = 0.192). On the contrary, the ratio was reversed in the
      control subjects (mean K1 = 0.109, mean k3 = 0.080). In addition, the patient's
      cerebellar metabolic rate of glucose (rCMRglu = 27.9 micromol/100 g/minute) and
      the rate constant of glucose egress (k2 = 0.543) were relatively increased
      compared with those of control subjects (mean rCMRglu = 21.9 micromol/100
      g/minute, mean k2 = 0.352). CONCLUSIONS: In a case of episodic bilateral
      cerebellar dysfunction caused by hypoglycemia, quantitative dynamic PET study
      demonstrated decreased glucose uptake-to-utilization ratio and increased leak of
      glucose in the cerebellum. The cerebellum is not invariably resistant to
      hypoglycemia.

PMID- 10932280
TI  - Aberrant neural circuits in malformations of cortical development and focal
      epilepsy.
AB  - Malformations of cortical development (MCD) account for a high proportion of
      medically resistant partial seizures in children and figure prominently in
      pediatric surgical series. In contrast to the results of epilepsy surgery for
      postnatally acquired lesions, seizure freedom in patients with MCD is less
      certain owing to difficulties in defining the epileptic zone, and fully excising
      the epileptogenic cortex. The authors present evidence that, compared with
      postnatally acquired lesions such as those due to tumors or trauma, focal
      epileptogenesis associated with MCD is best conceptualized as a disorder of
      widespread and patchy disturbance of cortical networks. This developmental
      perspective implies that the epileptogenic region in MCD is rarely discrete even
      in patients with focal anatomic lesions, and may include remote cortical or
      subcortical areas. Preoperative investigative protocols based on this model have
      improved surgical results, but outcome remains far from optimal and further
      progress in understanding the complex developmentally based features of MCD is
      required.

PMID- 10932281
TI  - Nonconvulsive focal inhibitory seizure: subdural recording from motor cortex.
AB  - The authors obtained an ictal electrocorticogram with chronically implanted
      subdural electrodes from a 30-year-old man with a low grade glioma in the right
      postcentral gyrus who had a focal inhibitory seizure of the left arm. During the
      ictal paresis, the authors observed epileptic discharges in the positive arm
      motor area of the right precentral gyrus and in its rostral area, but not in the
      negative motor area. The epileptic activity probably inhibited the spinal
      motoneuron pool without eliciting excitatory activity in the corticospinal
      pathway.

PMID- 10932282
TI  - Ictal urinary urge indicates seizure onset in the nondominant temporal lobe.
AB  - The authors describe six patients with medically refractory temporal lobe
      epilepsy whose seizures were characterized by an aura of ictal urinary urge. All
      seizures originated in the nondominant temporal lobe as evidenced from interictal
      spikes, ictal EEG, and MRI. Ictal SPECT, which was obtained in two patients,
      showed a hyperperfusion of the insular cortex, indicating a critical role of the
      insula for the generation of this symptom. Ictal urinary urge represents a new
      lateralizing sign indicating a seizure onset in the nondominant temporal lobe.

PMID- 10932283
TI  - APOE epsilon4 genotype is associated with an earlier onset of chronic temporal
      lobe epilepsy.
AB  - The authors analyzed the association between APOE epsilon4 genotype and clinical
      and MRI findings in 43 refractory temporal lobe epilepsy patients. The
      distribution of the alleles were normal. Ten patients (23%) had an APOE epsilon 4
      allele and had an earlier onset of habitual seizures (with epsilon4 5 +/- 5
      years; without epsilon4 15 +/- 10 years). Quantitative MRI findings were not
      influenced by the APOE epsilon4 genotype. APOE epsilon4 may shorten the latency
      between an initial injury and seizure onset.

PMID- 10932284
TI  - Plasma homocysteine and MTHFR C677T genotype in levodopa-treated patients with
      PD.
AB  - Plasma homocysteine and cysteine levels were measured in 90 patients with PD with
      the MTHFR C677T (T/T) genotype. The authors found that the levels of homocysteine
      a possible risk factor for vascular disease-were elevated by 60% in levodopa
      treated patients with PD, with the most marked elevation occurring in patients
      with the T/T genotype. Cysteine levels in subjects with PD did not differ from
      levels in control subjects. In the T/T genotype patients, homocysteine and folate
      levels were inversely correlated. Increased homocysteine might be related to
      levodopa, MTHFR genotype, and folate in PD.

PMID- 10932285
TI  - AIDS myelopathy is not associated with elevated HIV viral load in cerebrospinal
      fluid.
AB  - The pathogenesis of AIDS-associated myelopathy is unknown. Elevated HIV-1 viral
      load in CSF has been associated with cognitive impairment. The authors
      investigated if a similar association exists in patients with myelopathy. The
      authors evaluated levels of HIV-1 RNA in the CSF of 16 individuals with AIDS
      myelopathy and in 16 nonmyelopathic HIV-infected control subjects. There was no
      correlation between levels of HIV-1 RNA and the presence or severity of
      myelopathy.

PMID- 10932286
TI  - Functional outcomes after gamma knife thalamotomy for essential tremor and MS
      related tremor.
AB  - Twelve patients with a median age of 75 years underwent gamma knife thalamotomy
      for essential tremor (ET) (n = 9) or MS-related tremor (n = 3). All 11 evaluable
      patients noted improvement in action tremor. Six of eight ET patients had
      complete tremor arrest, and the violent action tremor in all three patients with
      MS was improved. One patient developed transient arm weakness. Stereotactic
      radiosurgery for ET and MS-related tremor is safe and effective for patients who
      may be poor candidates for other procedures.

PMID- 10932287
TI  - Cerebral ventricles are smaller in Hispanic than non-Hispanic patients with
      Alzheimer's disease.
AB  - MRI scans were compared between 71 Hispanic and 73 white non-Hispanic patients
      with National Institute of Neurological Disorders and Stroke probable AD.
      Analysis of covariance controlled for age, sex, education, and Mini-Mental State
      Examination scores indicated that ventricular size was smaller in Hispanic than
      white non-Hispanic patients (p = 0.0003). There was no difference in cortical
      atrophy and T2-weighted white matter hyperintense signals between groups.

PMID- 10932288
TI  - Retrospective analysis of the use of cyclosporine in myasthenia gravis.
AB  - The authors reviewed the records of patients with myasthenia gravis who took
      cyclosporine for at least 6 months between November 1987 and January 1999. Of 57
      patients who took cyclosporine for an average of 3.5 years, 55 (96%) had clinical
      improvement. The median time to best clinical response was 7 months.
      Corticosteroids were discontinued or decreased in 95% of 38 patients taking them.
      Major side effects included elevated serum creatinine (28%) and malignancy (11%).
      Five percent could not afford or tolerate the drug.

PMID- 10932289
TI  - Superficial CNS siderosis and spinal pilocytic astrocytoma.

PMID- 10932290
TI  - Anticipation in early- but not late-onset familial amyloid polyneuropathy (TTR
      met 30) in Japan.

PMID- 10932291
TI  - Cluster headache sine headache: case report.

PMID- 10932292
TI  - Influenza vaccine and the risk of relapse of Guillain-Barre syndrome.

PMID- 10932293
TI  - Isolated abducens nerve palsy caused by vascular compression.

PMID- 10932294
TI  - Musical hallucinations with dorsal pontine lesions.

PMID- 10932295
TI  - Remission of HIV myelopathy after highly active antiretroviral therapy.

PMID- 10932296
TI  - Amantadine-induced peripheral neuropathy.

PMID- 10932297
TI  - HLA-DQ1 associated with reflex sympathetic dystrophy.

PMID- 10932298
TI  - Myasthenia, thymoma, presynaptic antibodies, and a continuum of neuromuscular
      hyperexcitability.

PMID- 10932299
TI  - Neurologic complications associated with hepatitis C virus infection.

PMID- 10932300
TI  - Does HHV-8 have a neuroprotective role on the development of HIV encephalopathy?

PMID- 10932301
TI  - Immunization of college students against meningococcal disease.

PMID- 10932302
TI  - Cevimeline (Evoxac) for dry mouth.

PMID- 10932303
TI  - Hypnotic drugs.

PMID- 10932304
TI  - VHL gene inactivation in an endolymphatic sac tumor associated with von Hippel
      Lindau disease.

PMID- 10932305
TI  - No association between Glu/Asp polymorphism of NOS3 gene and ischemic stroke.

PMID- 10932306
TI  - Effectiveness of everyday occupations for changing client behaviors in a
      community living arrangement.
AB  - OBJECTIVE: This study examined the effect of three occupations-based
      interventions for reducing the frequency of dysfunctional behaviors (disruptive
      vocalizations, distraction of others, withdrawal from appropriate social
      interactions) in two women with dual (i.e., developmental, psychiatric)
      conditions. Additionally, the duration of time spent appropriately engaged was
      examined. METHOD: A single-subject, multiple baseline, across-subjects design,
      with two dually diagnosed residents in a Community Living Arrangement (CLA), was
      used to evaluate change in four behaviors under three alternating conditions.
      Condition 1 was CLA (morning and evening combined) compared with the school and
      sheltered workshop, Condition 2 was CLA morning, and Condition 3 was CLA evening.
      Intervention consisted of engagement in everyday occupations associated with the
      school-workshop and CLA settings as well as a positive reinforcement program.
      RESULTS: Using occupations-based interventions and a behavior modification
      program, 5 of 6 behaviors improved significantly in the school-and-workshop
      setting compared to the CLA, under Condition 1. Under Condition 2, the morning
      occupations-based intervention in conjunction with positive reinforcement for
      active participation significantly improved 4 of 6 behaviors for the two
      residents. Similarly, under Condition 3--the evening occupations-based
      intervention--4 of the 6 targeted behaviors improved significantly. CONCLUSION:
      The use of everyday occupations as interventions, in conjunction with positive
      reinforcement for active participation, was effective for decreasing
      dysfunctional behaviors and increasing functional behaviors in two women with
      dual conditions who resided in a CLA.

PMID- 10932307
TI  - Effects of occupational therapy services on fine motor and functional performance
      in preschool children.
AB  - PURPOSE: This study examined how performance components and variables in
      intervention influenced fine motor and functional outcomes in preschool children.
      METHOD: In a sample of 44 preschool-aged children with fine motor delays who
      received occupational therapy services, eight fine motor and functional
      performance assessments were administered at the beginning and end of the
      academic year. Data on the format and intervention activities of each
      occupational therapy session were recorded for 8 months. RESULTS: The children
      received a mean of 23 sessions, in both individual and group format. Most of the
      sessions (81%) used fine motor activities; 29% addressed peer interaction, and
      16% addressed play skills. Visual motor outcomes were influenced by the number of
      intervention sessions and percent of sessions with play goals. Fine motor
      outcomes were most influenced by the therapists' emphasis on play and peer
      interaction goals; functional outcomes were influenced by number of sessions and
      percent of sessions that specifically addressed self-care goals. CONCLUSION: The
      influence of play on therapy outcomes suggests that a focus on play in
      intervention activities can enhance fine motor and visual motor performance.

PMID- 10932308
TI  - Children with burn injuries: purposeful activity versus rote exercise.
AB  - OBJECTIVE: This study was designed to compare measures of pain when children with
      burn injuries were engaged in a purposeful activity, specifically a play
      activity, versus rote exercise. METHOD: Two 6-year-old children participated in a
      study using a single-subject, randomized multiple treatment design to compare two
      conditions: purposeful activity and rote exercise. Data were gathered for each
      session on four dependent measures: number of repetitions of therapeutic exercise
      completed, number and type of overt distress behaviors displayed, scores on self
      report scales of pain intensity, and overall enjoyment of the activity. RESULTS:
      Visual inspection of the graphed data suggested that, early in the rehabilitation
      process, the use of a play activity in comparison to rote exercise yielded better
      outcomes in terms of all four dependent measures. Additionally, the data implied
      that there may be a point later in the rehabilitation of a child with a burn
      injury when rote exercise may be as effective as play activities in meeting
      therapeutic goals. CONCLUSION: This study supports the belief that purposeful
      activity can yield results equal to or better than those achieved using rote
      exercise. Replication of this study is warranted, and the development is
      indicated of a measure of overt behavioral distress that is more appropriate than
      those currently available for children with burn injuries.

PMID- 10932309
TI  - Validating the Draw-A-Man Test as a personal neglect test.
AB  - OBJECTIVES: The purpose of this study was to determine the reliability and
      validity of a Draw-A-Man Test in measuring personal neglect in patients with
      right brain stroke. METHOD: Draw-A-Man Test was administered to 51 persons with
      right cerebrovascular accident (CVA) and 110 age-matched persons without brain
      insult. A categorical classification was developed based on the man drawn in the
      test. Participants who showed homogeneous bilateral representation of body parts
      were considered to not have personal neglect, whereas those who showed unilateral
      body parts were considered to have personal neglect. The completed tests were
      used to blindly categorize the persons with and without personal neglect
      according to the above definition by two raters for calculating interrater
      reliability. The Klein-Bell ADL (Activities of Daily Living) Scale was also
      administered to the participants with right CVA to validate the Draw-A-Man Test.
      RESULTS: This dichotomy--bilateral representation versus unilateral
      representation--showed a high percentage of agreement between two raters. Rater A
      classified all 110 "normal" participants as being without personal neglect and
      classified 13 of the 51 participants with stroke as having personal neglect.
      Participants demonstrating personal neglect showed significantly poorer ADL
      performance than did those without personal neglect. ADL performance was also
      found to be significantly related to somatosensation, motor status of the
      impaired limbs, and muscle strength of the sound limbs. However, even after
      controlling the effect of these variables by partial correlation, personal
      neglect was still highly related to ADL performance. CONCLUSION: The Draw-A-Man
      Test is a reliable and valid tool for discriminating clients with personal
      neglect from those without.

PMID- 10932310
TI  - The discovery of disability: a phenomenological study of unilateral neglect.
AB  - OBJECTIVE: Clients with right brain damage and unilateral neglect often lack
      awareness of their disabilities. This study examined how 4 participants with
      neglect experienced, discovered, and handled their disabilities in the context of
      their everyday life. METHOD: The 4 participants were interviewed five to seven
      times during their rehabilitation process. The data were collected and analyzed
      using the EPP (empirical, phenomenological, psychological) method. FINDINGS:
      Findings revealed seven features that described a discovery process for the 4
      participants. During this process, each participant began to discover and
      understand the consequences of her unilateral neglect in the performance of
      everyday tasks. This increased understanding was a prerequisite to being able to
      use compensatory strategies. CONCLUSION: By experiencing meaningful occupational
      situations, the participants gradually discovered and began to compensate for
      their disabilities in everyday life.

PMID- 10932311
TI  - COTA education and professional development: a historical review.
AB  - This article provides a historical review of certified occupational therapy
      assistant (COTA) education, professional roles, career mobility, and professional
      development. The evolution of COTA education from 2 hospital-based, 12-week
      training programs to the current 162 accredited 2-year college degree or
      professional certificate programs is examined. The expansion of the COTA role
      from well-delineated direct service provider to advanced practitioner able to
      assume leadership roles within the profession is explored. Historic and current
      programs and methods supportive of COTA career mobility and professional
      development goals, including the Career Mobility Program, continuing education,
      career laddering, and the Advanced Practitioner program are described.

PMID- 10932312
TI  - COTA to OTR: factors influencing professional development.
AB  - OBJECTIVE: This pilot study examined factors that influenced the pursuit of a
      professional educational degree by certified occupational therapy assistants
      (COTAs) seeking to become registered occupational therapists (OTRs). METHOD:
      Questionnaires were distributed to 92 COTAs attending a weekend professional
      occupational therapy education program. RESULTS: Although the stressors on these
      students were many, the depth and breadth of motivators, resources, and supports
      and the availability of weekend classes enabled this group of COTAs to pursue
      their professional development goal. Enabling the pursuit of professional degrees
      while working was viewed by the participants as essential to their professional
      development and career mobility. RECOMMENDATIONS: Strategies for meeting the
      diverse needs of COTAs and other nontraditional adult students seeking a
      professional degree in occupational therapy are identified and need to be
      supported by educators and practitioners. An increased appreciation of the
      challenges faced by these students and the development of innovative programming
      to meet their educational needs will strengthen the profession's ability to
      recruit and retain diverse, competent practitioners.

PMID- 10932313
TI  - Attitudes of occupational therapists toward spirituality in practice.
AB  - OBJECTIVE: This study examined (a) occupational therapists' attitudes about
      spirituality in practice on the basis of whether they identified themselves as
      religious, (b) whether their personal definition of spirituality related to their
      religiousness, (c) whether their definition related to their attitude about
      spirituality in practice, and (d) the methods they used to address the spiritual
      needs of clients. METHOD: An attitude questionnaire was developed and mailed to
      396 American occupational therapists. Fifty-two percent (n = 206) of the mailed
      questionnaires were analyzed. RESULTS: Overall, participants indicated a slightly
      positive attitude toward spirituality in occupational therapy practice.
      Participants who considered themselves to be religious indicated a more positive
      view toward spirituality in practice than those who did not consider themselves
      to be religious. Religiousness accounted for only 28% of the variance in choice
      of spirituality definition, indicating that additional variables account for what
      determines therapists' definitions of spirituality. No relationship was found
      between personal definition choice and attitude regarding spirituality in
      practice. The three methods most commonly used to address the spiritual needs of
      their clients were to (a) pray for a client, (b) use spiritual language or
      concepts with a client, and (c) discuss with clients ways that their religious
      beliefs were helpful. CONCLUSION: Therapists' conceptualization of spirituality
      and attitudes about spirituality in occupational therapy practice are quite
      diverse.

PMID- 10932314
TI  - Debate as a teaching strategy.

PMID- 10932315
TI  - Effects of billing Medicaid for occupational therapy services in the schools: a
      pilot study.

PMID- 10932316
TI  - Monitoring and documenting evidence during assessment and intervention.

PMID- 10932317
TI  - Skills training versus psychosocial occupational therapy: a reinterpretation.

PMID- 10932318
TI  - The value of postprofessional education.

PMID- 10932319
TI  - Relevant issues from a Latin's perspective.

PMID- 10932320
TI  - Characteristics of human chondrocytes, osteoblasts and fibroblasts seeded onto a
      type I/III collagen sponge under different culture conditions. A light, scanning
      and transmission electron microscopy study.
AB  - Hyaline cartilage has only a limited capacity of regeneration, thus, lesions of
      articular cartilage can lead to early osteoarthrosis. Current concepts in
      conservative orthopedic therapy do not always lead to satisfying results. As one
      new attempt to facilitate cartilage repair, autologous transplantation of
      articular chondrocytes is investigated in different assays. This study was
      designed to create a resistible and stable cell-matrix-biocomposite with viable
      and biosynthetically active human chondrocytes, osteoblasts or fibroblasts. This
      biocomposite might serve as an implant to treat deep osteochondral defects in the
      knee. We collected cartilage, spongiosa and skin probes from healthy patients
      undergoing hip-surgery and enzymatically liberated the chondrocytes, seeded them
      into culture flasks and cultured them until confluent. The spongiosa and the skin
      samples were also placed in culture flasks and cells cultured until confluent.
      After 4-6 weeks, cells were trypsinized and grown on a type I/III collagen matrix
      (Chondrogide, Geistlich Biomaterials, Wolhusen, Switzerland) for 7 days in
      standard Petri dishes and in a special perfusion chamber culture system. As
      controls, cells were seeded onto plastic surfaces. Then scaffolds were fixed and
      embedded for light microscopy and electron microscopy by routine methods. Light
      microscopically, chondrocytes grown on the surface of the scaffold form clusters
      or a dense layer of sometimes rather fibroblast-like and sometimes roundish,
      chondrocyte-like cells. Only a few cells grow deeper into the matrix. In
      transmission electron microscopy, the cells have a rather chondrocyte-like
      morphology which emphasizes the matrix-induced redifferentiation after
      dedifferentiation of chondrocytes in monolayer-culture in culture flasks.
      Chondrocytes on plastic surfaces have a spinocellular aspect with little signs of
      differentiation. Grown on Chondrogide, cells are more roundish and adhere firmly
      to the collagen fibrils of the scaffold. Osteoblasts grown on the collagen
      scaffold and examined by light microscopy form a thin cell-layer on the surface
      of the matrix with a reticular layer of dendritic cells underneath this sheet.
      Transmission electron micrographs show spinocellular and flat cells on the
      collagen fibrils. Scanning electron micrographs show large dendritic osteoblasts
      on plastic and a confluent layer of flattened, dendritic cells on the collagen
      scaffold. Fibroblasts form a thick multi-layer of typical spinocellular cells on
      the collagen matrix. Fibroblasts grown on plastic surfaces and examined by
      scanning electron microscopy also show a dense layer of fibroblast-like cells.
      For all three different types of cells no morphological differences could be seen
      when comparing cultivation in the perfusion culture system to cultivation in
      standard Petri dishes, although mechanical stress is believed to induce
      differentiation of chondrocytes. Especially the observed partially differentiated
      chondrocyte-matrix biocomposite might serve as an implant to treat deep cartilage
      defects, whereas osteoblasts and fibroblasts seem to be less suited.

PMID- 10932321
TI  - Effects of newly-developed benzodiazepine ligands on noise-induced mitochondrial
      damage in the rat.
AB  - In this study we measured the ability of three newly-synthesized N-arylalkylindol
      3-ylglyoxylylamide derivatives, which have recently been characterized as partial
      agonists at central benzodiazepine binding sites, to prevent the rat cardiac
      mitochondrial alterations resulting from acute loud noise exposure. In
      particular, we evaluated the effects of these new compounds on the
      ultrastructural damage induced by noise stress on the right atrium and ventricle
      after 6 and 12 hr of loud noise exposure. In parallel experiments, we measured
      the affinity of these compounds for peripheral benzodiazepine binding sites.
      Following a single injection of the test products, we observed a cardioprotective
      effect which was more marked after 6 hr compared with 12 hr of noise exposure.
      Confirming our recent data showing that full agonists at benzodiazepine receptors
      produce cardioprotection, we demonstrate in this study that partial agonists,
      like indolylglyoxylylamides, can also produce a cardioprotective effect. Based on
      their greater affinity in binding studies, the protective activity seems to be
      related more to their action at central than at peripheral benzodiazepine
      receptors.

PMID- 10932322
TI  - Distribution of capsaicin-sensitive substance P- and calcitonin gene-related
      peptide-immunoreactive nerves in bovine respiratory tract.
AB  - The distribution of nerve fibers immunoreactive for substance P (SP) and
      calcitonin gene-related peptide (CGRP) was examined by means of
      immunohistochemical methods in the respiratory tract from nose to lung of normal
      and capsaicin-treated cattle. SP- and CGRP-immunoreactive (IR) nerve fibers with
      varicosities were detected in all portions. They were more numerous in calves
      than in cows. They were abundant in the nasal and laryngeal mucosae and tracheal
      bronchus, and few in number in the lung. SP- and CGRP-IR nerve fibers were mainly
      seen in the epithelium, in connective tissue beneath the epithelium and around
      blood vessels, and in the glands throughout the respiratory tract. In contrast,
      SP- and CGRP-IR nerve fibers were sparse in the smooth muscle layer. Capsaicin
      treatment of neonates caused a remarkable reduction in the number of SP- and CGRP
      IR nerve fibers in the respiratory tract of calves. Double immunofluorescence
      experiments showed the colocalization of SP and CGRP in most of the nerve fibers.
      The present findings suggest that SP- and CGRP-IR nerve fibers are involved in
      the regulation of the bovine respiratory tract, and that capsaicin-sensitive SP-
      and CGRP-IR nerve fibers are sensory neurons of the bovine respiratory tract.

PMID- 10932323
TI  - Development of the pattern of dentition and dental laminae of Costa Rican
      plethodontid salamanders (Amphibia: Urodela).
AB  - The pattern of development of teeth and dental laminae of three Costa Rican
      plethodontids (Amphibia, Urodela, Plethodontidae) was investigated using
      transparent preparations, light microscopy and scanning electron microscopy. The
      teeth of the jaws are monostichously positioned, those of the posterior vomeral
      parts are polystichously arranged. The anterior vomeral parts carry
      monostichously positioned teeth at the caudal margin; yet, the adult Bolitoglossa
      subpalmata possesses two lines. As a sex dimorphism adult males display long
      monocuspid premaxillary teeth which protrude to the outside of the mouth cavity.
      All species studied possess paired dental laminae in the lower jaw. Nototriton
      abscondens possesses an unpaired dental lamina in the upper jaw, which is
      constricted between the unpaired premaxillary and the maxillaries. In contrast,
      the dental laminae in the upper jaw of B. subpalmata and Oedipina uniformis are
      segmented into a premaxillary and two maxillary laminae. All species possess a
      pair of anterior vomeral and a pair of posterior vomeral dental laminae in the
      adults, whereas the vomeral dental laminae of the subadults are unsegmented. The
      pattern of dentition is compared with that of Gyrinophilus and Eurycea.

PMID- 10932324
TI  - Effects of a combined thermochemotherapy on markers of apoptosis, differentiation
      and adhesion in the human mammary carcinoma MX-1. A light microscopic and
      immunohistochemical study.
AB  - The susceptibility to apoptotic stimuli, the degree of differentiation and the
      adhesive properties are important determinants of a tumor's biological behavior
      and of the possibility of it's being influenced by treatment. In this study we
      examined the effects of a combined thermochemotherapy, consisting of the
      administration of the alkylating agents ifosfamide or mafosfamide combined with
      hyperthermia at 41 degrees C for one hour, applied to the human mammary carcinoma
      MX-1. We concentrated our observations on the apoptosis-associated proteins bax
      and bcl-2, on cytokeratin and vimentin as markers of differentiation, on
      desmosomes and on the antiadhesive epithelial membrane antigen episialin. These
      proteins were visualized immunohistochemically in cultured cells in vitro as well
      as in xenotransplants growing in nude mice in vivo. We found that the
      susceptibility of the surviving cells to apoptotic stimuli, measured by the
      bax/bcl-2 ratio, was much higher after a combined thermochemotherapy than after
      chemotherapy or thermotherapy alone. Many of these cells could probably be forced
      into apoptosis by later applying another kind of anticancer therapy. With regard
      to the expression of episialin after thermochemotherapy, fewer cells possessed an
      antiadhesive and, therefore, potentially invasive capacity. The number of
      desmosomes seemed not to be affected. As to their higher expression of
      cytokeratin and their unchanged expression of vimentin, the surviving cells
      appear to be more differentiated. Since these results could be observed in vivo
      as well as in vitro, it seems likely that, apart from its influence on the
      perfusion of the tumor, the amplification of the cytostatic efficacy of the
      chemotherapy by hyperthermia must be mediated by a direct mechanism.

PMID- 10932325
TI  - Formation of cartilage in cardiac semilunar valves of chick and quail.
AB  - The development of cartilage in the aortic and pulmonary valves of chick and
      quail was studied using histological, histochemical and immunohistochemical
      techniques. In both species, the earliest evidence of chondrogenesis is the
      formation of smooth muscle alpha-actin-negative prechondrogenic (type II collagen
      negative) cellular condensations in the tunica media of the proximal aorta and
      pulmonary trunk, in front of or slightly distal to the valvular commissures. Such
      condensations are present as early as stage 37 of Hamburger-Hamilton in the
      aortic and pulmonary valves of the chick. In quail embryos, they form somewhat
      later, namely, at stage 38 in the aortic valves and stage 39 in the pulmonary
      valves. In the chick, synthesis of type II collagen starts in the central core of
      the aortic cellular condensations at stage 38. In the pulmonary valves of chick
      and aortic and pulmonary valves of quail, production of type II collagen does not
      begin until stage 40. This production then gradually increases toward the
      periphery of the condensations, which remain devoid of perichondrium prior to
      hatching. After birth, the condensations become transformed into hyaline
      cartilaginous foci. In the aortic valves of some chickens and quails, more or
      less extensive deposits of hyaline cartilage or fibrocartilage form along the
      attachments of the leaflets to their supporting sinuses. They develop later than
      the commissural cartilages. The present findings, together with previous data
      from the literature, suggest that the aortic and pulmonary valve cartilages
      differentiate from neural crest-derived nonmuscular cells.

PMID- 10932326
TI  - Ectopic adrenals in a sirenomelic fetus.
AB  - A sirenomelic malformation was diagnosed in a fetus from the first pregnancy of a
      25-year-old woman, and it was aborted at the 24th week of gestation. The fetus
      represented a sympus monopus. The head, organs of the neck, the thorax, and the
      upper part of abdominal cavity were normally formed. The kidneys, the ureters,
      the urinary bladder and the urethra were not developed. Adrenals of discoid shape
      and normal size were present in the normal position. The large bowel ended
      blindly in the sigmoid colon. Both testes were found in their normal position in
      the pelvis. Two symmetrical structures, resembling ovaries in shape and colour,
      were found near the testes. Histological examination established that these two
      organs were accessory (aberrant) adrenals.

PMID- 10932327
TI  - Delayed ectopic antler growth and formation of a double-head antler in the
      metacarpal region of a fallow buck (Dama dama L.) following transplantation of
      antlerogenic periosteum.
AB  - Autologous transplantation of antlerogenic periosteum to the metacarpal region of
      a fallow buck resulted in the formation of an ectopic pedicle within a few months
      after transplantation. In the following years the pedicle increased in size, but
      no ectopic antler development occurred. However, in the ninth year after
      transplantation a first antler of about 3 cm length grew from the ectopic
      pedicle. The hard ectopic first antler was not cast, and renewed antler growth,
      starting in late spring of the following year, led to the formation of a larger
      subsequent antler of 7.3 cm length. The latter exhibited a distal flattening
      (palmation) and a rudimentary basal coronet, thereby displaying morphological
      features typical of the subsequent antlers of fallow bucks. The results of the
      experiment indicate (1) that transformation from pedicle to antler growth can
      occur several years after pedicle initiation, when the pedicle has reached a
      certain threshold size, (2) that species and age specific features of antler
      morphology tend to be realized even in ectopic locations, and (3) that primary
      and subsequent antler growth was apparently triggered by cells of the pedicle
      periosteum, being derived from the transplanted antlerogenic periosteum. The
      findings thereby emphasize the importance of local factors in the control of
      pedicle/first antler transformation and antler morphogenesis.

PMID- 10932328
TI  - The "human"-like morphology of the swine papilla ilealis.
AB  - The morphology of the ileocecocolic transition, between the small and large
      intestine was studied in 33 male, adult pigs of unknown breed. The results were
      analyzed by the Wilcoxon Test (alpha < or = 0.05). The ileum opened into the
      large intestine, in all of the cases, at the level of the cecocolic junction in
      the form of a conical papilla (ileal papilla) turned towards the large intestine,
      with an oblique caudal and lateral direction, pointing to the cecal lumen. The
      cranial contour is higher than the caudal one, with average values of 3.0 cm, and
      1.5 cm in the fresh specimens and 2.8 cm and 1.4 cm after fixation of the
      specimens. The average diameter of the papilla apex was 1.5 cm, both in the fresh
      specimens and in the fixed ones. In 100% of the cases the ileal papilla appeared
      with a star-shaped orifice in its apex in both the fresh and in the fixed
      specimens. Our studies showed that the transition between the small and large
      intestine of the swine is ileocecocolic, thus similar to humans and different
      from the ileocecal (Perissodactyla, Rodentia, Lagomorpha) and, according to most
      descriptions, ileocolic (dog) transitions found in other animals.

PMID- 10932329
TI  - Arrangement of the tunica muscularis of the ileum, cecum and colon at the
      transition between the small and the large intestines of swine.
AB  - The arrangement of the bundles of muscular fibers in the transition between the
      small and the large intestines was studied in 12 male adult crossbred swine by
      dissection, after immersion in 50% nitric acid solution. The connection between
      the small and the large intestines was formed by the association of the muscular
      tissue, the connective tissue and the fat tissue. The tunica muscularis of these
      organs was organized in thin thread-like bundles and wide ribbon-like bundles of
      variable width and thickness. The superficial bundles of the longitudinal stratum
      of the tunica muscularis of the ileum established the continuity with the large
      intestine; the deep bundles penetrated into the ileal papilla. The limit between
      the cecum and the ascending colon was externally marked by the sulcus cecocolicus
      dorsalis and ventralis. The connection between the cecum and the ascending colon
      was formed by bundles of muscular fibers coming from the ileum, and the taeniae
      ventralis, lateralis and medialis of the cecum. Some bundles of muscular fibers
      from the ascending colon and the cecum headed toward the sulcus cecocolicus. The
      median bundles of muscular fibers of the taenia ventralis of the cecum, near the
      termination of the ileum, were arranged to form a loop around the termination of
      the ileum, mixing with the musculature of the ascending colon at the level of
      this junction.

PMID- 10932330
TI  - [Death is only a problem for the living. Human dignity and plastination].

PMID- 10932331
TI  - Introduction and evaluation of a modular seminar system in gross anatomy teaching
      at the Hannover Medical School.
AB  - We present a new modular seminar system which has been introduced into the gross
      anatomy teaching at the Hannover Medical School. It consists of seven modules
      with a clinical emphasis. The new modular seminar system was evaluated by an
      anonymous questionnaire. The results showed that the seminar system as a whole,
      and the different modules with one exception were highly appreciated by the
      students. The evaluation also revealed that the main reason for the success of a
      module is the manner of the teaching and learning rather than the clinical
      relevance. Taking into account the results of this evaluation we describe the
      appropriate style of teaching for use in a seminar. The success of this new
      approach to small group instruction in Germany should encourage other teachers of
      anatomy and other undergraduate subjects to consider new methods of teaching.

PMID- 10932332
TI  - The incremental validity of lumbar surface EMG, behavioral observation, and a
      symptom checklist in the assessment of patients with chronic low-back pain.
AB  - This study evaluated the comparative ability of lumbar surface EMG, behavioral
      observation, and a symptom checklist to correctly classify three groups of
      participants, (1) 18 patients with chronic low-back pain (CLBP), demonstrating
      excessive and/or anatomically inconsistent motor, sensory, and tenderness
      responses during a neurological examination, (2) 33 patients with CLBP exhibiting
      few or no inconsistent responses, and (3) 30 healthy matched controls.
      Discriminant analyses were used to develop predictive models. Correct
      classification rates for the individual assessments and all combinations of
      assessments were contrasted. Each modality predicted group membership
      significantly better than weighted chance (23%), with the symptom checklist
      approach having the highest individual correct classification rate (64%). The
      best combination of modalities was the symptom checklist and lumbar surface EMG
      (70% correct classification rate). The sensitivity and specificity of the
      individual assessments and all combinations of assessments are also presented.

PMID- 10932333
TI  - Asthma severity, psychophysiological indicators of arousal, and immune function
      in asthma patients undergoing biofeedback-assisted relaxation.
AB  - Asthma is characterized by airway hyper-responsiveness, inflammation, and
      reversible obstruction. Respiratory tract infection, allergies, air pollution,
      and psychosocial factors impact the severity and frequency of asthma symptoms.
      Pharmacotherapy and self-care are the major components in the management of
      asthma, but behavioral interventions also have the potential to affect asthma
      morbidity. We conducted a small, randomized controlled study, examining the
      effects of biofeedback-assisted relaxation in 16 nonsmokers with nonsteroid
      dependent mild asthma. Data were collected on asthma symptoms, pulmonary
      function, indicators of arousal, and cellular immune factors. The trained group
      evidenced a decrease in forehead muscle tension in comparison to the controls,
      but no changes in peripheral skin temperature. Decreases in asthma severity and
      bronchodilator medication usage for the experimental group were observed.
      Pulmonary function testing revealed a significant difference between groups in
      FEV1/FVC at posttest, with the E group having a higher ratio than the controls.
      The cellular immune data showed no significant group differences in total white
      blood cell or lymphocyte counts, but decreases over time were observed.
      Significant differences were observed in the numbers of neutrophils and basophils
      in the trained group compared to controls, which supports the concept of
      decreased inflammation. Results of delayed-type hypersensitivity skin testing
      suggested enhanced function, but they were not conclusive. These findings, though
      limited by size of population, suggest a positive effect of biofeedback-assisted
      relaxation in young, nonsteroid-dependent asthmatics. The mechanisms underlying
      linkages between psychological, behavioral, and immune responses in asthma
      require further study.

PMID- 10932334
TI  - Stress reduction by technology? An experimental study into the effects of
      brainmachines on burnout and state anxiety.
AB  - Stress and burnout are widely acknowledged as major causes of societal and
      individual problems in the Western world. In order to reduce material and
      immaterial expenses, increased efforts are made to enhance relaxation and stress
      reduction. Based on neuropsychological findings, alternative ways have been
      explored, one of them being the application of so-called brain wave
      synchronizers, which are said to induce a relaxation response by entraining alpha
      brain-wave activity (8-13 Hz) through audiovisual stimulation. A double blind,
      quasi-experiment was conducted among employees at a Dutch addiction care center
      to investigate the possible effects of two distinct brainmachine programs on
      burnout and anxiety. Subjects in both conditions showed a significant, immediate
      decrease in state anxiety as assessed by Spielberger's State-Trait Anxiety
      Inventory (STAI) and reported a range of subjective effects. However, a long-term
      effect on burnout, as measured with Maslach's Burnout Inventory (MBI-NL), could
      not be established. A long-term effect on anxiety (STAI), as investigated by
      interrupted time-series measurement, could not be established either. These and
      other findings suggest that the major claims with respect to these machines
      cannot hold over time, although pleasant short-term effects do occur. Individual
      differences in baseline responsivity, the stable character of burnout dimensions,
      or the ill-defined nature of relaxation, or a combination of these, may account
      for these results.

PMID- 10932335
TI  - Evaluation of a psychophysiologically controlled adaptive automation system,
      using performance on a tracking task.
AB  - Three experiments were conducted to evaluate the performance of a
      psychophysiologically controlled adaptive automation system. Subjects were asked
      to perform a compensatory tracking task while their electroencephalogram (EEG)
      was recorded and an engagement index was derived from the EEG, using the alpha,
      beta, and theta bandwidths: beta/(alpha + theta) and beta/theta. In Experiment I,
      EEG was recorded from three different sites: frontal, parietal, and temporal.
      Although tracking performance did not differ as a function of site, the number of
      task mode allocations was greater under a negative feedback contingency than
      under a positive feedback contingency. This effect was seen primarily from
      frontal sites. Experiments II and III evaluated the adaptive automation system,
      using extended runs under positive and negative feedback with either a slope
      (Experiment II) or absolute (Experiment III) criterion used to drive the system.
      Using either criterion, performance was found to be significantly better under
      negative feedback. Future evaluation and use of psychophysiologically controlled
      adaptive automation systems are discussed.

PMID- 10932336
TI  - A clinical study of visualization on depressed white blood cell count in medical
      patients.
AB  - This psychoneuroimmunological study examined the effects of visualization, or
      mental imagery, on immune system response, specifically, on depressed white blood
      cell (WBC) count in 20 medical patients. Subjects were 10 females and 10 males
      and included medical patients diagnosed with cancer, AIDS, viral infections, and
      other medical problems associated with depressed WBC count. Results indicated
      significant increases in WBC count for all patients over a 90-day period, after a
      predicted initial decrease in WBC count. No significant age or sex differences
      were found.

PMID- 10932337
TI  - [Tumor markers in pleural fluid].

PMID- 10932338
TI  - [Effect of output from jet nebulizers on PC20 values in asthmatic children].
AB  - This study aimed to assess the effects of two different nebulizer outputs on
      airway responsiveness to methacholine in asthmatic children. Twenty-seven atopic
      asthmatic children aged 6 to 14 years inhaled methacholine according to the
      Cockroft method until FEV1% had decreased 20% with respect to saline inhalation
      (PC20). The bronchial challenge tests were performed using two different types of
      jet nebulizer: Ava Neb 1780 and Hudson UP Draft II 1730, the outputs of which
      were 205 +/- 13 mg/min and 356 +/- 31 mg/min, respectively (p < 0.05). For 9 out
      of 27 patients (33%) the PC20 values were significantly different (one or more
      double concentrations) for the two nebulizers. However, 7 of those 9 children
      showed significantly lower bronchial responsiveness when the challenge tests were
      conducted with the low output jet nebulizer. This study suggests that using jet
      nebulizers with different outputs can markedly influence the results of
      methacholine challenge tests in asthmatic children. Such an influence could
      introduce significant bias in the assessment of bronchial responsiveness in
      comparative measurements in a single individual or in populations.

PMID- 10932339
TI  - [Mechanical and metabolic reproducibility of resistance test of expiratory
      muscles with incremental threshold loading].
AB  - BACKGROUND: The study of respiratory muscle endurance has mainly focused on
      inspiratory muscles. A new method to measure expiratory muscle endurance, through
      incremental threshold loading using a weighted plunger valve, has recently been
      described. OBJECTIVES: To evaluate the mechanical features of the plunger valve
      and the reproducibility of the method from the standpoint of both mechanics and
      metabolism. METHODS: Four untrained healthy subjects performed an incremental
      test with expiratory threshold loading (50 g every 2 min) on each of three non
      consecutive days; each test continued until the subject could no longer open the
      valve. Mouth pressure was recorded continuously during each test; on the first
      two test days, oxygen consumption (VO2) was also measured. RESULTS: Opening and
      closing pressures were the same and were independent of expiratory flow, with a
      linear load-pressure relationship (4 cmH2O) for every 10 g of weight). The
      maximal tolerated load (MTL) in the three tests was stable for two of the
      subjects, whereas the maximal load was reached by the other two subjects in the
      second and third tests, respectively. When MTL was reached in the third test,
      mean and peak mouth pressures (the latter expressed as percent of maximal
      expiratory pressure [MEP]) were 49 +/- 4% and 71 +/- 4%, respectively; the
      expiratory tension-time index measured at the mouth ([PMEANmouth/MEP] x
      [TE/Ttot]) was 0.25 +/- 0.02 (TE: expiratory time; Ttot: total time). In the
      first and second tests, we also measured oxygen consumption of the recruited
      muscles, which were mainly the expiratory muscles (VO2respmax); consumption in
      the last test was 213 +/- 65 ml O2/min (2.9 +/- 1.1 ml O2/kg/min). The
      intraindividual coefficient of variation ranged from 6.3% to 19.5% for the
      mechanical parameters and from 14% to 21% for the metabolic ones. CONCLUSIONS:
      The expiratory endurance test using a threshold valve allows quantification of
      muscle and metabolic reserve under incremental expiratory loads. The valve has
      appropriate mechanical characteristics for this purpose and reproducibility is
      acceptable, through the precise determination of the may require up to three
      tests.

PMID- 10932340
TI  - [Incidence of bronchopulmonary carcinoma in Castilla-Leon in 1997. Multicenter
      study of the Society of Castilla-Leon of Respiratory Pathology (SOCALPAR). Study
      Group for Bronchopulmonary Carcinoma of the SOCALPAR].
AB  - OBJECTIVES: Although lung cancer is the most frequently diagnosed tumor world
      wide, the real incidence of this diagnosis in Spain is unknown. To contribute to
      determining the incidence of lung cancer in this country, and in view of the lack
      of data from the community of Castilla-Leon, we carried out the present study.
      METHODS: The 56 members of the lung cancer research group of the Castillian
      Leonese Respiratory Disease Society (SOCALPAR) prospectively gathered data on new
      cases diagnosed in our community during 1997. Quality control checks were
      performed locally, at the central office for data management, and by way of
      reviews conducted at referral hospitals. RESULTS: One thousand fifteen cases (95
      women and 920 men) were diagnosed, giving an age-adjusted rate to world
      population of 21.53 cases per 100,000 inhabitants (men: 41.58; women: 4.31). The
      incidence of lung cancer by province of origin was 36.89 for Avila, 43.65 for
      Burgos, 42.07 for Leon, 38.88 for Palencia, 38.88 for Salamanca, 36.72 for
      Segovia, 29.91 for Soria, 45.90 for Valladolid, and 48.71 for Zamora. Smokers or
      ex-smokers accounted for 90.14% of patients with lung cancer. Diagnosis was by
      cytohistology for 877 patients (86.4%), with a predominance of squamous cell
      carcinoma (50.62%), and by clinical or radiologic assessment based on the
      pneumologist's or surgeon's criteria in 138 (13.6%). CONCLUSIONS: The
      standardized incidence of lung cancer in Castilla-Leon in 1997 was 21.53 cases
      per 100,000 inhabitants (men: 41.58; women: 4.31). Diagnosis was by clinical or
      radiological criteria in 13.6%.

PMID- 10932341
TI  - [Compliance with inhalation treatment of patients with chronic obstructive
      pulmonary disease].
AB  - OBJECTIVES: To evaluate patient compliance with inhaled medication therapy in
      chronic obstructive pulmonary disease (COPD), to identify determining factors and
      to propose corrective measures to improve compliance. METHODS: This was an open,
      observational, cross-sectional, non-comparative, single-measurement, non-random
      study. The inhalers were the Serevent Accuhaler, the Serevent Inhalador and the
      Flixotide Inhaler. Compliance was measured in four ways: a) difference in weight
      at the beginning and end of the study for all devices; b) dose counter reading
      for the Accuhaler; c) information from patient diaries (by days and by
      applications); and d) information from patient interviews using the Morinsky
      Green Test. Compliance was rated as follows: poor: < 50%, fair 51%-79%, good 80%
      119%, or "hypercompliant" > 120%. RESULTS: Seventy-two patients (mean age 65
      years) were enrolled. Compliance measured by weight was good in 77.1%, fair in
      11.5%, poor in 1.4% and hypercompliant in 10%. Compliance was good for the
      Accuhaler according to both weight (75%) and counted doses (83.3%). According to
      patient diaries, compliance was good when assessed by applications (98.8%) and by
      days (98.3%). According to the Morinksky-Green test, compliance was good for
      87.9%. CONCLUSIONS: Compliance was good as assessed by the methods used in this
      study. Patients who live in families, who enjoy a high socioeconomic level, have
      simple therapeutic regimens and have a good understanding of their disease and
      inhaler tend to have good compliance. Careful patient follow-up and good patient
      physician communication has improved compliance. However, follow-up studies are
      needed to check these results.

PMID- 10932342
TI  - [Infection and antibiotic use in COPD in primary care].
AB  - OBJECTIVES: The aim of this study was to know the opinion of Spanish primary care
      physicians regarding various aspects of diagnosis and treatment of chronic
      obstructive pulmonary disease (COPD), particularly with regard to bacterial
      infection in COPD. METHODS: A 20-item questionnaire about diagnostic and
      therapeutic aspects of COPD was distributed to 15,000 primary care physicians.
      The sample was stratified to be representative of Spanish geographic areas.
      Participation was voluntary and no incentive was provided; assurance of
      confidentiality of information given. A specially designed program was used for
      data analysis. RESULTS: Valid responses were obtained from 1,852 physicians
      (12.3%), 86% of whom were practicing in public clinics. Increased coughing with
      mucopurulent expectoration was considered the most important sign leading to
      suspicion of respiratory infection according to 70% of the respondents. The germs
      that primary care physicians thought responsible for infection in most cases were
      H. influenzae (83%), S. pneumoniae (79%), Pseudomonas (65%) and M. catarrhalis
      (61%). Antimicrobial spectrum was considered the main criterion for choosing an
      antibiotic (by 91%). The most frequently prescribed antibiotics were by order of
      preference: amoxicillin-clavulanic (50%), macrolides (24%), second and third
      generation cephalosporins (15%) and others. Mean duration of treatment was seen
      to be 10 days in nearly all cases. CONCLUSIONS: The primary care physicians
      surveyed were shown to have a good level of understanding of bacterial infection
      and its treatment in COPD.

PMID- 10932343
TI  - [Bronchodilation test in patients with stable COPD].

PMID- 10932344
TI  - [Biology of muscle injury and repair].

PMID- 10932345
TI  - [Pseudotumoral allergic bronchopulmonary aspergillosis].
AB  - Allergic bronchopulmonary aspergillosis (ABPA) develops as the result of a
      hypersensitivity reaction to fungi of the genus Aspergillus. Clinical and
      radiological presentation can be atypical, requiring a high degree of suspicion
      on the part of the physician who treats such patients. We report the cases of two
      patients with APBA in whom the form of presentation--with few asthma symptoms,
      images showing lobar atelectasia and hilar adenopathy--led to an initial
      suspicion of lung cancer.

PMID- 10932346
TI  - [Spontaneous intercostal pulmonary hernia: a case report].
AB  - In pulmonary hernia or pneumocele the lung protrudes through a defect in the
      chest wall. In this report of a case of spontaneous intercostal lung hernia, we
      describe the pathogenesis and classification of such hernias, including signs,
      symptoms, radiological findings and treatment methods. Our patient presented with
      severe chest pain at the base of the left hemithorax. A chest film and computed
      tomography of the region showed an left intercostal hernia. Surgical treatment
      was successful.

PMID- 10932347
TI  - [Pulmonary poisoning caused by maprotiline: report of a case].

PMID- 10932348
TI  - [Introduction of thoracic drainage tube in vena cava].

PMID- 10932349
TI  - [Reversibility of chronic air-flow obstruction].

PMID- 10932350
TI  - [Lung volume reductive surgery in patient using mechanical ventilation].

PMID- 10932352
TI  - Enhanced attachment of Bradyrhizobium japonicum to soybean through reduced root
      colonization of internally seedborne microorganisms.
AB  - Internally seedborne microorganisms are those surviving common surface
      sterilization procedures. Such microbes often colonize the radicle surface of a
      germinating soybean (Glycine max) seed, introducing an undefined parameter into
      studies on attachment and infection by Bradyrhizobium japonicum. Bacterial
      isolates from surface-sterilized soybean seed, cv. Williams 82 and cv. Maverick,
      used in our studies, were identified as Agrobacterium radiobacter, Aeromonas sp.,
      Bacillus spp., Chryseomonas luteola, Flavimonas oryzihabitans, and Sphingomonas
      paucimobilis. Growth of these microbes during seed germination was reduced by
      treating germinating seeds with 500 micrograms/mL penicillin G. The effects of
      this antibiotic on seedling development and on B. japonicum 2143 attachment,
      nodulation, and nitrogen fixation are reported here. Penicillin G treatment of
      seeds did not reduce seed germination or root tip growth, or affect seedling
      development. No differences in nodulation kinetics, nitrogen fixation onset or
      rates were observed. However, the number of B. japonicum attached to treated
      intact seedlings was enhanced 200-325%, demonstrating that other root-colonizing
      bacteria can interfere with rhizobial attachment. Penicillin G treatment of
      soybean seedlings can be used to reduce the root colonizing microbes, which
      introduce an undefined parameter into studies of attachment of B. japonicum to
      the soybean root, without affecting plant development.

PMID- 10932351
TI  - Molecular analysis of variability within the toxigenic Aspergillus ochraceus
      species.
AB  - Genetic variability of Aspergillus ochraceus was examined at the DNA level. Based
      on the HaeIII-Bg/II generated mitochondrial DNA restriction profiles, most
      isolates could be classified into two distinct groups. These two groups could
      also be distinguished by the random amplified polymorphic DNA technique, and with
      telomeric PCR amplifications. Phylogenetic analysis of sequences of the
      intergenic transcribed spacer region of some of the strains resulted in a
      dendrogram with the same topology as that based on mitochondrial DNA and
      amplified DNA data. None of the isolates with type 2 mtDNA profiles produce
      ochratoxins. Some strains (e.g., A. ochraceus ICMP 939) displayed strain-specific
      mitochondrial DNA patterns, and their amplified DNA profiles were also different
      from all other A. ochraceus strains examined.

PMID- 10932353
TI  - Biodiversity of killer activity in yeasts isolated from the Brazilian rain
      forest.
AB  - The occurrence of killer activity against a panel composed of 22 industrially and
      (or) medically important yeasts was investigated in 438 yeast and yeast-like
      cultures belonging to 96 species, isolated from different environments of the
      Brazilian rain forest. Altogether, 26% of ascomycetes, 56% of basidiomycetes, and
      42% of yeast-like cultures exhibited killer activity against at least one of the
      panel yeasts. More than 15 species never reported before as toxin producers were
      found, with Pseudozyma antarctica, Trichosporon asteroides, and Geotrichum
      klebahnii, showing the broader activity spectra. Plasmid curing did not cure the
      killer phenotypes of Candida maltosa, Debaryomyces hansenii, G. klebahnii, Tr.
      asteroides, Cryptococcus laurentii, and Ps. antarctica.

PMID- 10932354
TI  - Airborne microfungi from eastern Canadian sawmills.
AB  - Working in sawmills is associated with bioaerosol exposure and respiratory health
      problems. This study is the first to analyze the mycoflora of eastern Canadian
      sawmills and the nature of airborne contamination at different work sites. Fifty
      work sites (debarking, sawing, planing, and sorting) within 17 sawmills were
      sampled for airborne microfungi. One thousand seven hundred strains were
      isolated, quantified to determine the frequency of occurrence, and then
      identified. Unlike the European studies, we did not frequently identify the
      presence of fungi that were described in European sawmills as being related to
      respiratory health problems. In eastern Canadian sawmills, Penicillium species
      are the most frequently isolated microfungi.

PMID- 10932355
TI  - Phenotypic characterization of the Xenorhabdus bacterial symbiont of a Texas
      strain of the entomopathogenic nematode Steinernema riobrave, and
      characterization of the Xenorhabdus bovienii bacterial symbiont of a Newfoundland
      strain of Steinernema feltiae.
AB  - Two bacterial symbionts of entomopathogenic nematodes, one of which originated
      from Texas, U.S.A., and the other from Newfoundland, Canada, were characterized
      phenotypically. These strains belonged to the genus Xenorhabdus. The Newfoundland
      (NF) strain was shown to be X. bovienii but the Texas (TX) strain was not
      identified at the species level. Four additional cultures of Xenorhabdus were
      included in the study. These were a strain of X. bovienii (Umea), which was from
      a nematode of European origin, and strains of X. nematophilus, X. beddingii, and
      X. poinarii. The tests used in this study indicated identical properties for the
      NF (North American) and Umea (European) strains of X. bovienii. These could be
      differentiated from the other strains studied by their failure to grow at 34
      degrees C and resistance to low concentrations of a mixture of amoxilline and
      clavulanic acid. The Xenorhabdus TX strain could be differentiated from the other
      strains studied by its failure to grow at 10 degrees C. Of the tests done,
      approximately 30 were useful in distinguishing between the strains and species
      studied.

PMID- 10932356
TI  - Bacterial dynamics in first year sea ice and underlying seawater of Saroma-ko
      Lagoon (Sea of Okhotsk, Japan) and resolute passage (High Canadian Arctic):
      inhibitory effects of ice algae on bacterial dynamics.
AB  - The seasonal development of bacterial abundance in first year bottom ice and
      underlying seawater were studied at Saroma-ko Lagoon in Hokkaido, Japan, and at
      Resolute Passage in the High Canadian Arctic during the algal bloom in spring
      1992. The aim of this study was to evaluate whether the high algal concentrations
      reached during the bloom of ice algae have inhibitory effects on bacterial
      dynamics. Bacterial abundance (measured as total cell count and colony-forming
      units CFU) increased with the increase of the algal biomass up to 500 micrograms
      Chla.L-1 in both locations. Culturable fraction (measured as the percentage of
      CFU counts versus the total cell counts) was between 7% and 22% at Saroma-ko, and
      approximately 0.08% at Resolute Passage. When algal biomass exceeded 500
      micrograms of Chla.L-1, both bacterial abundance and culturable fraction
      decreased significantly. There was a maximum threshold of algal biomass (between
      500 and 800 micrograms of Chla.L-1) after which bacterial dynamics become
      negatively coupled to the algal biomass. These results suggest that bactericidal
      and/or bacteriostatic compounds from these extremely high algal concentrations
      could explain the decrease in bacterial abundance and culturability in bottom ice
      observed after the ice algae bloom.

PMID- 10932357
TI  - Purification and characterization of a common soil component which inhibits the
      polymerase chain reaction.
AB  - DNA prepared from soil usually contains a brown-tinted inhibitor of the
      polymerase chain reaction (PCR) which limits the sensitivity of this technique
      for specific detection of microorganisms. To localize the inhibitor, soil
      fractions were tested for their inhibitory effect on the PCR reaction. A highly
      inhibitory activity, sufficient to account for the inhibition typically exhibited
      by soil DNA, was found to be tightly associated with the soil microorganism
      fraction. After cell breakage, the inhibitory material became soluble, and was
      not separable from DNA by standard purification procedures. A method was derived
      by which most of the inhibitory material could be selectively solubilized from
      the microorganism fraction without cell breakage, using successive washes with
      buffers differing in EDTA concentration. This technique was used to isolate a
      substance with characteristics suggesting that it is the major PCR inhibitor
      contaminating DNA purified from soil. It was found to be an organic, water
      soluble compound of high molecular weight, and was present in a variety of soil
      types from different locations. It was found to be distinctly different in its
      solubility properties from humic and fulvic acids, and also in its FT-IR and NMR
      spectra. It forms a complex with protein and may inhibit the PCR reaction by an
      interaction with Taq DNA polymerase.

PMID- 10932358
TI  - Cometabolic biotransformation of nitrobenzene by 3-nitrophenol degrading
      Pseudomonas putida 2NP8.
AB  - A strain of Pseudomonas putida (2NP8) capable of growing on both 2-nitrophenol
      and 3-nitrophenol, but not on nitrobenzene (NB), was isolated from municipal
      activated sludge. 2-Nitrophenol was degraded by this strain with production of
      nitrite. Degradation of 3-nitrophenol resulted in the formation of ammonia. Cells
      grown on 2-nitrophenol did not degrade nitrobenzene. A specific nitrobenzene
      degradation activity was induced by 3-nitrophenol. Ammonia, nitrosobenzene, and
      hydroxylaminobenzene have been detected as metabolites of nitrobenzene
      degradation by cells grown in the presence of 3-nitrophenol. These results
      indicated a NB cometabolism mediated by 3-nitrophenol nitroreductase.

PMID- 10932359
TI  - Changes in the metabolism of the microalga Chlorella vulgaris when coimmobilized
      in alginate with the nitrogen-fixing Phyllobacterium myrsinacearum.
AB  - In an agroindustrial wastewater pond, a naturally occurring unicellular
      microalga, Chlorella vulgaris, was closely associated with the terrestrial plant
      associative N2-fixing bacterium Phyllobacterium myrsinacearum. When the two
      microorganisms were artificially coimmobilized in alginate beads, they shared the
      same internal bead cavities, and the production of five microalgal pigments
      increased, but there were no effects on the number of the cells or the biomass of
      the microalga. The association, however, reduces the ability of C. vulgaris to
      remove ammonium ions and phosphorus from water. The bacterium produced nitrate
      from ammonium in synthetic wastewater with or without the presence of the
      microalga, and fixed nitrogen in two culture media. Our results suggest that
      interactions between microalgae and associative bacteria should be considered
      when cultivating microalgae for wastewater treatment.

PMID- 10932360
TI  - Host cell invasion and intracellular residence by Aeromonas salmonicida: role of
      the S-layer.
AB  - Virulent strains of the fish pathogen Aeromonas salmonicida, which have surface S
      layers (S+), efficiently adhere to, enter, and survive within macrophages. Here
      we report that S+ bacteria were 10- to 20-fold more adherent to non-phagocytic
      fish cell lines than S-layer-negative (S-) mutants. When reconstituted with
      exogenous S-layers, these S- mutants regained adherence. As well, latex beads
      coated with purified S-layers were more adherent to fish cell lines than uncoated
      beads, or beads coated with disorganized S-layers, suggesting that purified S
      layers were sufficient to mediate high levels of adherence, and that this process
      relied on S-layer structure. Gentamicin protection assays and electron microscopy
      indicated that both S+ and S- A. salmonicida invaded non-phagocytic fish cells.
      In addition, these fish cells were unable to internalize S-layer-coated beads,
      clearly suggesting that the S-layer is not an invasion factor. Lipopolysaccharide
      (which is partially exposed in S+ bacteria) appeared to mediate invasion.
      Surprisingly, A. salmonicida did not show net growth inside fish cells cultured
      in the presence of gentamicin, as determined by viable bacterial cell counts. On
      the contrary, bacterial viability sharply decreased after cell infection. We thus
      concluded that the S-layer is an adhesin that promotes but does not mediate
      invasion of non-phagocytic fish cell lines. These cell lines should prove useful
      in studies aimed at characterizing the invasion mechanisms of A. salmonicida, but
      of limited value in studying the intracellular residence and replication of this
      invasive bacterium in vitro.

PMID- 10932361
TI  - Amylase hyper-producing haploid recombinant strains of Thermomyces lanuginosus
      obtained by intraspecific protoplast fusion.
AB  - Amylase hyper-producing, catabolite-repression-resistant, recombinant strains
      were produced by intraspecific protoplast fusion of thermophilic fungus
      Thermomyces lanuginosus strains, using well-characterized, morphological, and 2
      deoxy-D-glucose resistant markers. The fusant heterokaryons exhibited enhanced
      amylase activities as compared to the amylase hyper-producing parental strain
      (T2). Diploids derived from heterokaryons segregated to stable haploid
      recombinant strains. In the haploid strain (Tlh 4q), approximately 5-fold higher
      specific activities of alpha-amylase and glucoamylase in the culture filtrate
      were observed as compared to the wild-type strain (W0).

PMID- 10932362
TI  - Co-culture of Aeromonas salmonicida and host cells in intraperitoneal implants is
      associated with enhanced bacterial survival.
AB  - An experimental procedure that we named "in vivo co-culture technology" allowed
      us to study the interactions between Aeromonas salmonicida and host cells, inside
      semipermeable chambers implanted in the peritoneal cavity of Atlantic salmon.
      Intraperitoneal implants containing bacteria and host cells, or bacteria and
      lysed cells, consistently yielded higher numbers of viable bacteria than implants
      containing bacteria only. Electron microscopy confirmed that 30 min after chamber
      inoculation, numerous bacteria were already internalized by exudate cells, and
      that at 3 h, destruction of these cells was evident. Thus, the rapid invasion and
      (or) the A. salmonicida-mediated lysis of host cells may constitute a survival
      strategy in vivo. The co-culture of bacteria with exudate peritoneal cells may be
      applicable to the in vivo study of other pathogens.

PMID- 10932363
TI  - Survival of Escherichia coli in freshwater: beta-D-glucuronidase activity
      measurements and characterization of cellular states.
AB  - A rapid enzyme assay measuring beta-D-glucuronidase activity of Escherichia coli
      was tested in survival experiments after discharge of E. coli in river water.
      Enzyme activity was compared with several analyses performed to characterize
      cellular states under stressful conditions. Enzyme activity remained stable under
      starvation and light stress conditions despite losses of culturability,
      respiratory activity, and cytoplasmic membrane integrity. beta-D-Glucuronidase
      activity followed the pattern of genetic and morphologic cell integrity. The
      tested enzyme assay seems well adapted to study the fate of fecal coliforms in
      survival experiments, and appears to be a rapid and efficient way to estimate the
      microbiological quality of surface waters.

PMID- 10932364
TI  - [Compatibility, indications, and limits of nerve sparing technique in lateral
      pelvic lymphadenectomy for advanced rectal carcinoma].
AB  - The aim of radical surgical treatment of rectal cancer is to control the spread
      and prevent recurrence of the disease. In an attempt to improve the results of
      treatment of locally advanced rectal cancer, we advocate an extended surgical
      approach consisting of total mesorectal excision, lateral pelvic lymphadenectomy
      and the nerve sparing technique with resection of autonomic nerves whenever these
      fibers are affected by locally advanced tumor. Nine cases (9.2%) in a personal
      series of 98 patients with rectal carcinoma, operated on over the period from
      January 1992 to December 1997, underwent total mesorectal excision, lateral
      pelvic lymphadenectomy and the nerve sparing technique procedures for locally
      advanced extraperitoneal disease. In 7 patients with stage II or III disease, the
      5-year survival rate was 80% and the 5-year disease-free survival rate 66.7%
      after a mean follow-up of 55 months. None of them experienced local recurrence,
      but one patient died of diffuse metastatic disease 50 months after surgery. One
      patient with stage IV rectal cancer died of disease 13 months postoperatively,
      while another patient with the same stage of disease is still alive with disease
      26 months after surgery. One patient underwent liver resection for a solitary
      metastasis 25 months after the primary operation. Two patients suffered
      postoperatively from urinary retention with mild irregular flow at urodynamic
      testing, but no long-term urinary disturbances persisted. Retrograde ejaculation
      occurred postoperatively in one of the two patients who experienced urinary
      disorders, and another patient had erection disturbances. These sexual
      dysfunctions did not improve during long-term follow-up. Total mesorectal
      excision, lateral pelvic lymphadenectomy, and the nerve sparing technique, with
      resection of the autonomic nerves whenever these fibers are involved, allow
      satisfactory results to be achieved in terms of survival and functional outcome
      in patients with locally advanced rectal cancer. In western subjects, however,
      this procedure is safe only after careful patient selection.

PMID- 10932365
TI  - [Immediate and long-term results in ileoanastomosis with reservoir in 335
      consecutive cases].
AB  - Restorative proctocolectomy with ileal pouch anal anastomosis is the first choice
      procedure for the treatment of ulcerative colitis and familial adenomatous
      polyposis. The introduction of the stapled technique has shortened the duration
      of the procedure and reduced the complication rates. Data on 335 consecutive
      patients undergoing ileal pouch anal anastomosis for ulcerative colitis (277
      pts), Indeterminate colitis (20 pts) and familial adenomatous polyposis (38 pts)
      between 1984 and 1998 were prospectively collected. Parameters evaluated included
      diagnosis, surgical technique, functional outcome, early and late complications
      and their management and results. Twenty-nine patients (8.6%) presented with
      pelvic sepsis. Twelve patients (3.5%) experienced late perianal fistulas. The
      pouch failure rate was 3.4%. Six patients required a re-do pouch procedure, with
      75.9% preservation of sphincter function. No correlation was found between
      complication rates and diagnosis. The mean number of stools was 5.2/24 h. The
      study confirmed the safety and effectiveness of the procedure. In particular,
      morbidity rates are comparable to those of major abdominal procedures and the
      long-term functional results are satisfactory. However, a number of technical
      aspects, such as the anastomosis technique, the need for temporary ileostomy and
      the treatment of indeterminate colitis, still remain controversial.

PMID- 10932366
TI  - [Current indications for sublobar resection in non-small-cell bronchogenic
      carcinoma].
AB  - Over the past 30 years, there has been considerable controversy regarding the
      role of segmental and wedge resections in the management of stage I (T1-T2N0M0)
      non-small-cell lung cancer. Recently, a prospective randomized trial (Lung Cancer
      Study Group, 1995) revealed unfavorable results after limited resection, which,
      in early stage lung cancer, remains a reasonable option for patients with
      compromised pulmonary reserve, especially those in whom a previous contralateral
      resection has been performed. The following report describes the role of limited
      resection in the management of patients with T1-T2N0 non-small-cell lung cancer
      and presents a retrospective review of our series of 125 limited resections out
      of 1356 resections performed for lung cancer. In particular, long term survival
      and the frequency of local/regional recurrence were noted in 92 cases operated on
      with a curative intent. 26.6% vs 12.5% local/regional recurrence rates were
      observed among patients undergoing limited resections for T2 and T1 lung cancer,
      respectively. The five year survival in the limited resection group was 13.5% for
      T1 and 60% for T2 vs 51% and 72% in the standard procedure group, respectively.
      The lobectomy results were superior to those of sublobar resection. The latter
      should be reserved for patients in poor general condition contraindicating a
      standard lobectomy.

PMID- 10932367
TI  - [Palliative treatment of neoplasms of the bilio-pancreatic area. Surgical
      diversion treatment versus endoscopic-percutaneous approach].
AB  - Bilio-pancreatic (BPD) tumours are pathologies with an overall resectability rate
      of 20-25%, with a high percentage of patients directed towards palliative
      treatment (70-90%). One hundred and twenty-eight patients underwent palliative
      treatment for BPD tumours. The M:F ratio was 1:1.5 and the mean age 61 years. The
      tumours were topographically divided into: 84 (63%) localised in the pancreatic
      head region; 34 (25%) biliary duct tumours and 6 arising in the ampulla of Vater.
      42 patients (30%) underwent palliative surgical treatment (group 1) and 86 (70%)
      received non-surgical treatment (endoscopic percutaneous) (group 2). We also
      performed 6 gastrointestinal by-passes (GEA). The early morbidity rate was 36% in
      the first group and 12.8% in the second. The incidence of late morbidity in the
      first group was nil, with a mean survival of 10 months. Mortality was nil in both
      groups. Surgical by-pass is advisable in the presence of patients with a longer
      life expectancy and in good clinical condition but presents a high rate of early
      morbidity and a low percentage of late complications. The authors conclude that
      validity of the methods is similar. They believe that, in selected cases,
      surgical treatment remains the therapy of choice for BPD tumours.

PMID- 10932368
TI  - [New development in Crohn's disease: ++unravelling the mystery and its
      reinstatement as a surgically treatable condition. Part 2. Potential
      etiopathogenesis of "terminal ileitis" and extension of the disease to mesenteric
      small intestine and the colon].
AB  - INTRODUCTION: The aetiopathogenesis of terminal ileitis is still unknown, as is
      the cause of its spread to the small and large bowel. The aim of this study was
      to shed light on these unknown aspects of Crohn's disease. CONCLUSIONS: The lack
      of patency of the ileal branch of the ileocolic lymphatic collector which causes
      terminal ileitis, usually in the earlier part of life, is likely to occur in the
      foetus around the 10th week of pregnancy as a result of a minor abnormality of
      the physiological regression of the vitelline duct. Excessive atrophy of the
      lymphatic network seems to occur, also affecting the rudimentary lymphatic
      vessels in the midgut destined to become the terminal ileum. The terminal ileitis
      spreads to the large bowel in an increasing percentage of cases and is directly
      related to duration of the disease, causing first ileitis plus right colitis, and
      then ileitis plus total colitis (which, however, does not include the rectum). It
      may also include the jejunum, causing skip lesions. This spread of lesions is not
      due to any genetic predisposition (that is to say, it is not predetermined in
      empirical terms), but rather to the extent of the lymphatic obstruction caused by
      the spread of immunocomplexes via the lymphatic network. This is shown by the
      fact that secondary lesions of the jejunum and large bowel are also typical of
      lymphoedema and that their spread is segmentary. In the light of these
      pathogenetic mechanisms, it is reasonable to assume that the spread of the
      process from the ileum to the colon might be prevented by prompt surgery during
      the initial phase of the ileitis. If these views are correct, the traditional
      subdivision of Crohn's disease forms into ileitis, ileocolitis and solitary
      colitis should be replaced by a very simple scheme showing the spread of the
      primary ileitis very often to ileocolitis, first confined to the right colon and
      then total. We cannot include either solitary colitis (not clearly defined in the
      literature) or anorectal Crohn's disease (whose forms have yet to be fully
      acknowledged) in this scheme.

PMID- 10932369
TI  - Analysis of deaths due to injury in Milano: preliminary results.
AB  - We reviewed all trauma deaths occurring in the urban area of Milan during one
      year. Autopsy reports were cross-referenced with pre- and in-hospital records and
      the Injury Severity Score was calculated by a senior surgeon. Causes of deaths
      were defined as central nervous system injury (CNS), hemorrhage (HEM), combined
      central nervous system injury and hemorrhage (CNS + HEM), and burns (BURN).
      Places of death were considered the scene (DOS), during transportation (DOA), the
      emergency room (DER), and hospital. Two multidisciplinary commissions reviewed
      patient reports and deaths were judged non-preventable, possibly preventable or
      frankly preventable, using the unanimous decision rule. The TRISS method was used
      to calculate the probability of survival for in-hospital deaths. Overall trauma
      deaths were 255 with 78.04% blunt and 16.08% penetrating traumas. Burns accounted
      for 5.88%. CNS and CNS + HEM caused 171 (67.05%) deaths. DOS were 91, DOA 48, DER
      34, and in-hospital deaths 33. Victims found dead (49 individuals) were excluded
      from further analysis. The commissions classified 56.31% of deaths as non
      preventable, 32.03% as possibly preventable and 11.65% as frankly preventable.
      The Injury Severity Score decreased from DOS to in-hospital deaths (p < 0.05).
      The preventability rate was higher for in-hospital deaths (p < 0.05). The results
      of this study suggest that the development of a tiered trauma system in Milan is
      mandatory.

PMID- 10932370
TI  - Flexible sigmoidoscopy as a colorectal cancer screening test in the general
      population: recruitment phase results of a randomized controlled trial in
      Lombardia, Italy.
AB  - A two arm multicentre randomized controlled trial is in progress to evaluate the
      efficacy of flexible sigmoidoscopy (FS) as a screening test for colorectal cancer
      in the general population. AIMS: To determine the acceptance rate and feasibility
      of FS as a colorectal cancer screening test in average-risk asymptomatic
      volunteers. Average-risk, asymptomatic subjects, aged 55-64 years and assisted by
      244 general practitioners (GPs) in Lombardy, Italy, were invited by postal
      questionnaire (PQ) to enter a study for the prevention of colorectal cancer and
      asked to indicate their interest in, and willingness to undergo, screening: those
      responding positively were randomized to the intervention or control arms. GPs
      were trained in colorectal cancer screening and proposed free FS to their
      patients randomized to the intervention arm. All sigmoidoscopies were performed
      by experienced endoscopists. Small polyps were removed at FS. Colonoscopy was
      indicated for high risk polyps (size more than 5 mm, more than two adenomas,
      villous histology, severe dysplasia or malignancy). 40,945 subjects were invited.
      667 PQs were returned undelivered due to postal failure. 7,892 (19.59%) subjects
      responded, 2,116 of whom (26.81%) were not included, presenting 1 or more
      exclusion criteria. We randomized 5,778 volunteers and performed 1,582
      sigmoidoscopies out of 2,885 subjects in the intervention arm (54.84% acceptance
      rate). Although the screening procedure had a good attendance rate in the
      intervention group, involvement of the people invited was lower than expected.
      Future FS screening programmes will require a keener focus on recruitment
      strategies, mainly with participation of GPs.

PMID- 10932371
TI  - Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of
      the pancreas.
AB  - Recent reports have demonstrated an improvement in 5-year actuarial survival of
      patients with resected ductal adenocarcinoma. The purpose of this study was to
      determine the factors favoring long-term survival after pancreaticoduodenectomy.
      Between 1974 and 1995, 75 patients with pancreatic head carcinoma underwent
      pancreaticoduodenectomy in our department. The overall postoperative mortality
      rate was 5.3% and morbidity was 24%. Median survival following resection was 17
      months. The estimated 1-, 2- and 5-year survival rates were 68%, 46.7% and 18.7%,
      respectively. Five-year survival was significantly greater for node-negative
      versus node-positive patients (41.7% vs 7.8%, P < 0.001), for smaller (< 3 cm)
      versus larger tumours (33.3% vs 8.8%, P < 0.006), and for negative versus
      positive resection margins (23.3% vs 0, P < 0.001). Other factors, including
      gender, age, and blood transfusion had no significant effect on survival. The
      multivariate analysis was done using the Cox proportional hazards model to
      determine independent prognostic determinants of survival. The presence of
      positive resection margins was the strongest independent predictor of decreased
      survival. Lymph node metastasis, tumour size > 3 cm, and poor histologic
      differentiation were also independent predictors of poor survival. The most
      favorable subset consisted in 17 patients who had negative resection margins,
      negative lymph nodes, and tumor size < 3 cm. Their 5-year survival rate was
      52.9%.

PMID- 10932372
TI  - [Is cell-mediated immunity affected by laparoscopic cholecystectomy?].
AB  - It is well known that surgery significantly decreases cell-mediated immunity.
      Laparoscopic cholecystectomy is a so-called minimally invasive surgical
      procedure, and on the basis of this consideration we investigated whether and how
      the immune system is modified in patients after laparoscopic cholecystectomy
      compared to those undergoing open cholecystectomy. Immune activity (neutrophils,
      total lymphocyte count, lymphocyte subpopulations, multiple skin tests) was
      evaluated in 82 patients on postoperative day 1 and on postoperative days 1, 3
      and 6. Forty-two patients underwent open cholecystectomy and 40 laparoscopic
      cholecystectomy. On postoperative day 1 patients treated by open cholecystectomy
      showed a significant increase (P < 0.05) in plasma neutrophils, whereas this
      parameter was unchanged in patients undergoing laparoscopic cholecystectomy. Skin
      tests revealed a hypo- or anergic response in the majority of patients (81.8%)
      undergoing open surgery compared to those treated laparoscopically (10.5%). Total
      lymphocyte count and lymphocyte subpopulations were normal in the two groups.
      Four cases of respiratory tract infection (4.8%) were detected after open
      cholecystectomy. Laparoscopic cholecystectomy substantially reduces postoperative
      pain and hospitalisation, promotes an earlier recovery and return to normal
      activity and is not associated with postoperative immunosuppression, with a more
      positive postoperative morbidity profile compared to open surgery.

PMID- 10932373
TI  - [1,000 prosthetic hernia repairs: experience of a dedicated team].
AB  - The authors report on their 8-year experience with inguinal prosthetic repair.
      Their personal experience includes 1000 hernioplasties, 639 of which performed
      using the "plug and patch" technique. The postoperative morbidity was 2.7% and
      patients were unsatisfied only in 1.8% of cases (self-evaluation test). Follow-up
      was carried out by means of phone enquiries supplemented by a clinical
      examination in selected cases and in a control group of asymptomatic patients.
      85.4% of the study population and 94.8% of patients operated on in the last 38
      months were contacted by phone. The recurrence rate after "plug and patch" repair
      was statistically adjusted according to the maximal bias test, taking into
      account the percentage of patients lost to follow-up. Other late complications
      were severe neuralgia (0.9%) and rejection of the prosthesis (0.1%). Migration of
      the plug was never observed. The authors confirm that the aims of inguinal hernia
      surgery (significant reduction of recurrences and minimal discomfort for the
      patient) can be best achieved in suitable facilities (hernia centres) by a
      dedicated team of experienced professionals.

PMID- 10932374
TI  - [Crossectomy in the treatment of great saphenous vein insufficiency: a developing
      technique].
AB  - Crossectomy is an old and simple surgical technique for great saphenous vein
      insufficiency. At present the results in the international literature are not
      encouraging, possibly owing to a lack of standardized indications. The authors
      describe their experience. Crossectomy with phlebectomy of collaterals or
      perforating veins was performed (cross < 8 mm) in 132 patients. The mean follow
      up was 21 months in 71 patients: subjective results (patient's opinion) were
      satisfactory to good in 81% for symptoms and in 77% for cosmetic results
      (disappearance of varicose veins). Objective results (surgeon's opinion) were
      less satisfactory: recurrent varicose veins were observed in 17 patients (23%:
      teleangectasias or truncal varices) and a residual saphenous reflux at color
      coded doppler ultrasonography was still present in 43 patients. Postoperative
      saphenous reflux did not correlate closely with symptoms, suggesting that
      crossectomy may improve venous pump function even if reflux is not totally
      abolished. Crossectomy requires further investigation for evaluation of long term
      results; more accurate indications and preoperative screening may further improve
      the success rate of this simple technique.

PMID- 10932375
TI  - Ultrasonographic detection of portal branches and hepatic vein gas associated
      with mesenteric artery occlusion: a new finding correlated with patient
      prognosis?
AB  - The diagnosis of bowel infarction is still a challenge. In some cases, portal
      venous gas is an associated feature and in these patients, the prognosis is very
      poor. We report on our experience with two consecutive cases in which
      ultrasonography showed gas in the portal venous branches, and also in the hepatic
      veins in one of them. At laparotomy, advanced bowel necrosis was found, and both
      patients died within 24 hours. Other cases of portal venous gas associated with
      bowel infarction have been reported, but this is the first report of gas also
      being found in the hepatic veins. There may be a relationship between the amount
      of gas in the intrahepatic veins and the stage of bowel ischemia. Confirmation of
      this might improve the selection of patients and eliminate unnecessary
      procedures.

PMID- 10932376
TI  - [Videothoracoscopic approach in the treatment of intralobar pulmonary
      sequestration. Report of a case].
AB  - The Authors report on the use of a videothorascopic approach in the treatment of
      a patient with intralobar bronchopulmonary sequestration. The latter is a rare
      malformation which more often than not manifests itself in young patients with
      hemophthisis, recurrent infection and cough. The condition is difficult to
      diagnose and is often diagnosed intraoperatively. The treatment is surgical
      resection. The videothorascopic approach was used in a young patient presenting a
      lesion of the left inferior lobe with polycyclic contours suspected of being an
      intralobar bronchopulmonary sequestration, along with medical history findings of
      cough and hyperpyrexia. The approach permitted identification of the lesion in
      the context of the left inferior lobe, safe identification and section of the
      abnormal systemic vessel supplying the lesion and subsequent inferior lobectomy.
      The postoperative course was uneventful and the patient was discharged on
      postoperative day 5 with an excellent esthetic and functional outcome. The
      videothorascopic approach should be taken into consideration for the diagnosis
      and treatment of intralobar bronchopulmonary sequestrations.

PMID- 10932378
TI  - Day surgery: the value of monitored anesthesia care and intraoperative
      monitoring.
AB  - Recently an increasing percentage of patients is receiving care and surgical
      procedures in Day Surgery (DS), undergoing local or loco-regional anesthesia
      techniques, to which many patients appear to be rather reluctant and show fear
      and anxiety. The anesthesiologist can resolve this problem administering i.v.
      hypnotic and analgesic drugs and adjusting their level to patient's needs and
      type of surgery. They increase the patient's compliance to DS care and contribute
      to its diffusion. Nowadays, commonly used drugs permit quick changes of
      anesthesia depth with a fast and safe recovery but these require an appropriate
      monitoring in order to prevent and rapidly detect the onset of complications. In
      this study we analyze the peculiarity of Monitored Anesthesia Care and the
      appropriate intraoperative monitoring especially regarding the use of pulse
      oximetry.

PMID- 10932377
TI  - [Incidental diagnosis of seminoma in male infertility: report of a clinical
      case].
AB  - The aims of the study were to evaluate the association between male infertility
      and risk of developing testis cancer and to establish guidelines for the early
      diagnosis of testis neoplasia in subfertile men. 32-year-old infertile man. The
      patient underwent random testicular biopsy to establish the exact cause of
      infertility. An incidental diagnosis of seminoma was made and the patient then
      underwent right testis excision. Anatomopathologic macroscopic examination
      revealed two nodules, the sizes of which were 0.8 x 0.4 and 0.3 x 0.2 cm,
      respectively. Histologic examination confirmed the diagnosis of typical seminoma,
      pT1, with copious lymphocytic struma infiltration. There appears to be a
      correlation between male infertility and occurrence of seminoma. Diagnosis of
      testis cancer is often incidental and sometimes occurs in men undergoing
      testicular biopsy to investigate infertility. Since the biopsy was not
      specifically targeted in our case, the diagnosis of seminoma was casual. This
      suggests the need for a careful follow-up, including testicular ultrasonography
      as a screening test to achieve an early diagnosis of testis cancer in all
      infertile men, because of their higher risk of developing testis cancer than the
      normal population.

PMID- 10932379
TI  - 4th Congress of the European Haematology Association. Barcelona, Spain, June 9
      12, 1999. Abstracts.

PMID- 10932380
TI  - Instructional Conferences: IV. Interventional Gastroenterology, XIII Clinical
      Gastroenterology, XVI Physicians of Infectious Diseases. Inflammatory Diseases
      and Pancreatic Neoplasms. April 13-14, 2000. Abstracts.

PMID- 10932381
TI  - American Telemedicine Association 4th annual meeting in cooperation with the US
      Department of Defense Telemedicine and Advanced Technology Research Center
      National Aeronautics and Space Administration. Salt Lake City, Utah, USA. April
      18-21, 1999. Abstracts.

PMID- 10932383
TI  - Position and histological structure of the testes in the brown hare (Lepus
      europaeus) during seasonal regression and recrudescence.
AB  - The position and histological structure of the testes of 33 brown hares (Lepus
      europaeus) were studied from July to December. From July to September, the testes
      were located in the scrotum; in October and November, in some animals, the testes
      were positioned more or less in the inguinal canal towards the abdominal cavity,
      and in December none of the investigated animals had testes located in the
      scrotum. Testes were weighed and a quantitative analysis of tissue components was
      performed: the diameter of the seminiferous tubules, the depth of the
      seminiferous epithelium, the thickness of the tunica albuginea, the thickness of
      the peritubular tissue and the relative proportion of seminiferous tubules were
      determined. The tunica albuginea and peritubular tissue were thickest in
      September, October and at the beginning of November. In the same months the
      testis weight was low, and the diameter of the seminiferous tubules, the depth of
      the seminiferous epithelium and the relative proportion of seminiferous tubules
      in the testis tissue were significantly lower than in other months. We did not
      find any correlation between testicular regression or testis weight reduction and
      the change in the position of the testes. During recrudescence of spermatogenesis
      in November and December the testes were located in the inguinal canal.

PMID- 10932382
TI  - Lateral musculature in the whitemouth croaker (Micropogonias furnieri): its
      characterization with respect to different gonadal conditions.
AB  - Histochemical and ultrastructural studies were performed on the lateral
      musculature from individual female whitemouth croaker, Micropogonias furnieri, at
      the anterior, medium and posterior regions. Based upon histochemical myosin
      ATPase (m-ATPase) determination, diverse types of red, pink and white fibres were
      discerned. Red muscle had abundant mitochondria and stained intensely for aerobic
      enzymes, white muscle scarcely stained for the same enzymes and pink muscle
      responded in an intermediate manner. Both white and pink muscle had few
      mitochondria. The relative proportion of red muscle increased towards the caudal
      region; pink muscle diminished towards this region and white muscle modified its
      proportion only in the anterior region. m-ATPase activity showed differences in
      relation to the gonadal condition along the body, particularly in the white
      fibres at the anterior and medium regions.

PMID- 10932384
TI  - Differential localization of immunoreactive alpha- and beta-subunits of S-100
      protein in feline testis.
AB  - This study investigates the differential localization of the alpha-subunit (S100
      alpha) and the beta-subunit (S100-beta) of the S-100 protein in the feline
      testis, using immunohistochemistry with polyclonal antibodies to bovine S-100
      protein (S-100) and monoclonal antibodies to bovine S100-alpha and S100-beta.
      Appreciable differences were observed in the cellular localization of the
      immunoreactivity of each subunit. S-100 was observed in the Sertoli cells, the
      epithelial cells of the transitional segment of the seminiferous tubules, Leydig
      cells and the peritubular cells of the seminiferous tubules, but was not observed
      in the epithelial cells of straight tubules and the rete testis or in the
      endothelial cells of blood and lymph vessels. S100-alpha immunoreactivity was
      localized in Sertoli cells, peritubular cells and the epithelial cells of the
      terminal segment of the tubules, whereas S100-beta immunoreactivity was localized
      in Leydig cells. The differential localization of the alpha- and beta-subunits of
      the S-100 protein in the feline testis suggests that this protein is
      multifunctional and be useful as an investigative tool in studying feline testis
      function.

PMID- 10932385
TI  - [Anatomic-topographic description of the stomach, small intestine, large
      intestine and their arteries of the greater mara (Dolichotis patagonum Desmarest
      1820)].
AB  - The abdominal parts of the alimentary canal and the associated arteries from
      seven male and nine female maras are described. The mara possesses a stomach with
      a single cavity and a glandular mucosa lining. The large stomach is situated
      caudal of the liver at right-angles to the longitudinal body axis. The long
      jejunum is located on the left side of the body caudal of the stomach. The cecum
      has two teniae and numerous haustra which are proximal larger than distal. The
      smooth colon ascendens runs proximal parallel to the cecum and describes distal
      an U-shaped double-loop. The internal surface of the proximal part of the colon
      ascendens is characterized by two parallel mucosal ledges. Cecum and colon
      ascendens lie right caudal of the liver. The colon descendens is coiled and
      situated on the left body side. The A. gastrica sinistra and branches of the A.
      lienalis and the A. hepatica supply the stomach. The A. mesenterica cranialis
      which branches of separately from the A. coeliaca is a large and long vessel that
      supplies the major parts of the small intestine and the colon. The A. mesenterica
      caudalis supplies parts of the colon desendens and of the rectum.

PMID- 10932386
TI  - Expression of neuropeptide Y and neuropeptide Y Y1 receptors and neuronal markers
      following axotomy in the rat spinal cord and gracile nucleus.
AB  - Using immunocytochemistry, the effects of denervation on the expressions of the
      neuropeptide Y Y1 receptor, neuropeptide Y and neuronal markers were investigated
      in the lumbar spinal cord of the rat. Ten, 17 and 24 days after unilateral
      sciatic nerve section, the distribution of the neuropeptide Y Y1 receptor was
      seen in lamina II in the ipsilateral and contralateral side of the lumbar spinal
      cord and gracile nucleus, whereas neuropeptide Y immunoreactivity located
      strongly in laminae I-II and moderately in laminae III-IV in the ipsilateral
      side. Denervation, following section of the sciatic nerve, resulted in no change
      in the distribution of the neuropeptide Y Y1 receptor in the spinal cord. This
      suggests that the neuropeptide Y that is expressed in myelinated afferents
      following nerve section does not affect the expression of this receptor. This is
      particularly apparent in the gracile nucleus which shows clear neuropeptide Y
      staining following sciatic nerve section and no expression of the neuropeptide Y
      Y1 receptor.

PMID- 10932387
TI  - Light and scanning electron microscopic studies of the nasal turbinates of the
      horse.
AB  - The nasal turbinates of 5 young horses were studied by light and scanning
      electron-microscopy. Stratified cuboidal epithelium lined the rostral part of the
      dorsal and ventral nasal turbinates of the vestibular region. The polyangular
      microvillus cells of this region were separated by linear depressions. The mid
      and caudal parts of the dorsal and ventral nasal turbinates and the rostral part
      of the ethmoturbinates were lined by pseudostratified columnar ciliated
      respiratory epithelium. Numerous cilia with dilated blebs on the ciliated cells
      concealed adjacent non-ciliated supporting cells and goblet cells. The olfactory
      zone consisting of the olfactory vesicle and a dense network of olfactory cilia
      localized to the caudal part of the ethmoturbinates. The three regions were
      delineated from each other by transitional zones.

PMID- 10932388
TI  - [Construction principles in the forepaw and hindpaw of the domestic cat (Felis
      catus). 1: Skeleton].
AB  - The differences in the skeleton of the forepaw and hindpaw of the domestic cat
      are an expression of a highly specialized, functional adaption: The mesaxonic
      forepaw with abducable first digit is used for running as well as for catching
      and climbing. The paraxonic hindpaw becomes, particularly through the arched
      construction of the metacarpus, a long and strong caulking tool both in sprinting
      and climbing up. The discussion focuses on evolutionary considerations. Moreover,
      common points and differences in the skeleton of the forepaw and hindpaw of the
      domestic cat and their importance are summarized and briefly compared with the
      situation in the dog.

PMID- 10932389
TI  - The surface features of the epithelial lining of the ducts of the epididymis of
      the ostrich (Struthio camelus).
AB  - The luminal appearance of the various ducts of the epididymis of the ostrich was
      studied by scanning electron microscopy in tissues fixed by immersion in
      glutaraldehyde. The ductal types were similar to those previously described for
      some other species of birds. Numerous short microvilli, as well as a single
      cilium, projected from the apical surface of the rete testis cell. The ciliated
      cells of the efferent ductules projected tufts of cilia into the ductal lumen,
      while the non-ciliated cells bore short microvilli. The connecting and epididymal
      ducts were lined by a columnar cell type whose apical surface bore uniformly
      distributed microvilli and a single, centrally situated cilium. The spermatozoa
      found in all ducts of the epididymis bore a distal cytoplasmic droplet. This
      observation has implications for the maturational process in the ostrich
      spermatozoon in the epididymis. The surface features of the ducts, except for a
      few noteworthy differences, were generally similar to those previously described
      for the male domestic fowl, turkey and duck.

PMID- 10932390
TI  - Mass treatment/prophylaxis during an outbreak of infectious syphilis in
      Vancouver, British Columbia.

PMID- 10932391
TI  - [Chaos and dynamic instability in microbiological systems. A mathematical
      microbiological reflection in the international year of mathematics].

PMID- 10932393
TI  - [Pathogenicity of Enterococcus spp. Characteristics of 169 hospital isolates].
AB  - BACKGROUND: To know the characteristics of Enterococcus spp. strains isolated in
      the hospital; to analyse the importance of this microorganism and its resistance
      to antimicrobial agents. PATIENTS AND METHODS: Retrospective analysis of the case
      histories of 169 patients with Enterococcus spp. isolates, selected at random at
      the Infanta Cristina Hospital in Badajoz. Investigation was carried out on: age,
      date of admission and discharge, clinical symptoms, risk factors, previous
      antibiotic treatment, clinical and microbiological evolution, recommended
      treatment and prescribed treatment. Identification of microorganisms and
      antibiogram with Pos Combo 41 microScam panels, read on Baxter WalkAway-40
      equipment. RESULTS: The most frequently found species was Enterococcus faecalis.
      In 75 cases the isolations were polymicrobial. The enterococci were isolated
      mainly from urinary infections (27%), skin infections (20%), intrabdominal
      infections (14%) and infections from surgical wounds (14%). The existence of
      peripheral catheter was the main risk factor. All the strains of E. faecalis were
      susceptible to the glycopeptides. Two strains of Enterococcus faecium were not
      susceptible to vancomycin and one of these was not susceptible to teicoplanin.
      Mortality was from 21-27.5%. CONCLUSIONS: Enterococcus spp. is frequently
      isolated in nosocomial infections, although in approximately half the cases it is
      associated with other bacteria. For this reason, it is not always possible to
      determine its pathogenic contribution. The isolated strains, except two strains
      of E. faecium, are susceptible to vancomycin. A relation exists between high
      resistance to aminoglucosides and resistance to fluoroquinolones.

PMID- 10932392
TI  - [Safety of liposomal amphotericin B in patients with high risk of
      nephrotoxicity].
AB  - BACKGROUND: Amphotericin B is the medication of choice in systemic or invasive
      fungal infections, but its use often is limited by nephrotoxicity. Lipid
      formulations of amphotericin B have reduced this risk, but it is not known if
      these medications also prevent the deterioration of kidney function in patients
      with previous kidney failure or at risk of kidney failure, such as newborns and
      patients treated with cyclosporine A. METHOD: A retrospective analysis was made
      of epidemiological, clinical and analytic data collected from the clinical
      histories of patients with previous renal failure or at high risk of
      nephrotoxicity who were treated with liposomal amphotericin B at our hospital
      between January 1991 and January 1997. RESULTS: An analysis was made of 23
      patients (15 men and 8 women, mean age 38 years) who met established criteria.
      All had severe immunosuppression. Twelve patients had been treated previously
      with conventional amphotericin B, but treatment was interrupted for kidney
      failure. The other 11 patients in the group received cyclosporine A (9 cases) or
      were at risk of nephrotoxicity because of their underlying disease or situation
      (2 cases). No deterioration of kidney function due to liposomal amphotericin B
      was observed in any patient. In 5 of the 12 patients who had deterioration of
      kidney function as a result of previous use of conventional amphotericin B and
      lived more than one week after changing treatment, it was observed that kidney
      function recovered and baseline creatinine levels were reached. CONCLUSIONS: Our
      findings suggest that liposomal amphotericin B can be used safely in
      immunocompromised patients with fungal infection who have failure or high risk of
      kidney failure.

PMID- 10932394
TI  - [Seroepidemiological study of hepatitis A in Gran Canaria (Spain)].
AB  - BACKGROUND: The aim of this study was to assess the seroprevalence and the risk
      factors of hepatitis A virus (HAV) infection in the population from Gran Canaria
      (Spain) and to determine at which age pre-vaccination testing would be useful.
      METHODS: A transversal observational study of the presence of HAV antibodies
      (IgG) on serum samples obtained from a population ranging from 8 months to 63
      years old was performed between January 1995 and December 1996. IgG anti-HAV were
      detected by a commercial immunoenzyme assay. The study included 547 persons
      resident in Gran Canaria. Epidemiological data (age, sex, number of family
      members, educational level, urban/rural residence and previous history of
      hepatitis) were gathered through a personal interview. Confusing variables were
      excluded by mean a multiple logistic regression analysis. RESULTS: Global
      prevalence of anti-HAV (IgG) was 36.0% (CI 95% 32.0-40.0). The prevalence of anti
      HAV increased significantly with age from 2.3% in children under 4 years until
      98.9% in older than 40 years (OR 3956.0; CI 95% 241.7-64,753.5). Only three
      independent data (age, sex and educational level) were significantly associated
      with HAV seroprevalence. A previous history of hepatitis A was present only in
      4.8% of HAV-positive subjects. CONCLUSIONS: The low prevalence of anti-HAV (IgG)
      in persons under 25 years old suggest that in the adolescent population the
      implementation of universal vaccination programs is recommended even without
      previous serologic screening. Otherwise, the results suggest that HAV
      prevaccination screening in our geographical were must be limited to subjects
      older than 25 years.

PMID- 10932395
TI  - [Usefulness of detecting Mycobacterium tuberculosis by genome amplification in
      the diagnosis of childhood pulmonary tuberculosis].
AB  - OBJECTIVE: To evaluate the polymerase chain reaction in the diagnosis of
      pulmonary tuberculosis in children. PATIENTS AND METHODS: 135 samples (68 sputum
      and 67 gastric aspirates) of 72 patients under 15 years old with suspected
      tuberculosis and a negative acid-fast stain were included in the study. In all
      the samples an acid-fast stain and culture in Lowestein-Jensen with and without
      piruvate were performed. Also, a specific detection of Mycobacterium tuberculosis
      complex (MT) was made by PCR (Amplicor-MT-Roche Diagnostic). Tuberculosis was
      certainly diagnosed when M. tuberculosis was isolated or clinical evidence of
      tuberculosis in positive-PCR cases with negative culture was achieved. RESULTS:
      Ten samples of six patients were positive culture. Four of these samples were
      positive PCR. In addition, two samples of two patients with negative culture were
      positive PCR. Both patients had a clinical diagnosis of pulmonary tuberculosis
      with effective anti-tuberculosis treatment, one of them had also another positive
      PCR and culture sample. The results of sensitivity, specificity, positive
      predictive value and negative predictive value by patient according to the
      reference methodology were 57.1, 100, 100 and 95.4%, respectively, and by sample
      66.6%, 100, 100 and 96.8%, respectively. Other 15 patients presented pulmonary
      tuberculosis with negative PCR and culture; so the sensitivity of the culture and
      the PCR regarding a clinical diagnosis were 27.3% (6/22) and 18% (4/22)
      respectively. CONCLUSION: Due to the diagnosis by culture takes a long time and
      the low percentage of samples of pediatric patients with positive acid-fast rain
      stain, the PCR would be useful in order to achieve quickly and specific diagnosis
      of tuberculosis in a high-prevalence population.

PMID- 10932396
TI  - [Respiratory syncytial virus infection in adult patients hospitalized with
      community-acquired pneumonia].
AB  - OBJECTIVE: To determine the incidence and distribution of infection caused by
      respiratory syncytial virus (RSV) in hospitalized adults with community-acquired
      pneumonia. PATIENTS AND METHODS: Patients were immunocompetent adults
      hospitalized with community-acquired pneumonia, who were prospectively studied in
      our hospital. As a part of the diagnostic protocol, we performed RSV serology
      with paired acute and convalescent phase sera of patients admitted between
      February 1995 and May 1997. Clinical and epidemiological characteristics of
      patients with and without acute infection were compared. RESULTS: Paired RSV
      serology was performed in 250 patients hospitalized with community-acquired
      pneumonia. 97% of them had presence of IgG antibodies but only 17 patients (6.8%)
      had serologic evidence of acute infection; of these, seroconversion was observed
      in eight and positive IgM in nine. Fourteen cases with acute infection (82%)
      occurred between November and May. Three patients had pneumococcal pneumonia, 2
      Legionella pneumophila and 12 pneumonia of unknown etiology. There were no
      clinical differences between patients with and without RSV acute infection but
      those with acute infection had more frequently bilateral involvement in chest
      radiography and a greater proportion of pneumonias of unknown etiology.
      CONCLUSIONS: RSV is a cause of acute infection among adults hospitalized with
      community-acquired pneumonia, mainly between November and May. Further studies to
      assess the role of RSV as a causative agent of pneumonia in this population are
      needed.

PMID- 10932397
TI  - [Stomatococcus mucilaginosus infections. Bibliographic review].

PMID- 10932398
TI  - [Febrile syndrome evolved over a long period and dementia].

PMID- 10932399
TI  - [Ocular trauma in a 35 year old male].

PMID- 10932400
TI  - [Central nervous system tuberculomas seen on positive SPECT in a patient with
      AIDS and multiresistant tuberculosis].

PMID- 10932401
TI  - [Chagas disease: another cause of cerebral mass occurring in patients with
      acquired immunodeficiency syndrome].

PMID- 10932402
TI  - [Etiology of urinary tract infections in a tertiary hospital].

PMID- 10932403
TI  - [Acute renal insufficiency with complication of acute infection by Coxiella
      burnetii].

PMID- 10932404
TI  - [Mononucleosis syndrome with a clinical presentation of Q fever].

PMID- 10932405
TI  - [Protozoan diarrhea in patients with positive serology for the human
      immunodeficiency virus at the time of highly-active retroviral treatment].

PMID- 10932407
TI  - [Chronic osteomyelitis caused by Staphylococcus lugdunensis].

PMID- 10932406
TI  - [Spontaneous bacterial peritonitis produced by Enterococcus faecium].

PMID- 10932408
TI  - [Pelvic inflammatory disease caused by Chlamydia trachomatis as a cause of
      ascites].

PMID- 10932409
TI  - [Diagnostic procedures in Chlamydia pneumoniae infections].

PMID- 10932410
TI  - Introduction: health technology assessment and the European Union.
AB  - Health technology assessment (HTA) has become increasingly important in the
      European Union as an aid to decision making. As agencies and programs have been
      established, there is increasing attention to coordination of HTA at the European
      level, especially considering the growing role of the European Union in public
      health in Europe. This series of papers describes and analyzes the situation with
      regard to HTA in the 15 members of the European Union, plus Switzerland. The
      final paper draws some conclusions, especially concerning the future involvement
      of the European Commission in HTA.

PMID- 10932411
TI  - Health technology assessment in Austria.
AB  - The Austrian healthcare system relies mainly on physicians in private practice
      and on various services provided by hospitals. The social health insurance scheme
      is compulsory, covering 99% of the population. The system is very decentralized.
      While the federal state provides the framework, the nine autonomous provinces are
      responsible for administering health and social services. There is ongoing public
      discussion about centralizing the healthcare system to make it more efficient and
      to enforce structural reforms. Because of concerns about healthcare expenditures,
      in 1997 the Performance-Related Hospital Financing System (LKF), a system similar
      to the diagnosis-related group system, was introduced for hospitals, including a
      plan for large medical devices. It is too early to evaluate the success of this
      new system, although some effects of the LKF system that could have been
      anticipated, such as shortened lengths of stay and more hospitalizations, have
      been seen. Previously, health technologies have been almost uncontrolled in
      Austria. The evaluation of health technologies as an instrument to support or to
      control their dissemination and use or to help define policies is not
      institutionalized or systematically used. It seems clear that structural reforms
      of the Austrian healthcare system are needed. Health technology assessment should
      be part of such reforms.

PMID- 10932412
TI  - Health technology assessment in Belgium.
AB  - The Belgian healthcare system has a Bismarck-type compulsory health insurance,
      covering almost the entire population, combined with private provision of care.
      Providers are public health services, independent pharmacists, independent
      ambulatory care professionals, and hospitals and geriatric care facilities.
      Healthcare responsibilities are shared between the national Ministries of Public
      Health and Social Affairs, and the Dutch-, French-, and German-speaking Community
      Ministries of Health. The national ministries are responsible for sickness and
      disability insurance, financing, determination of accreditation criteria for
      hospitals and heavy medical care units, and construction of new hospitals. The
      six sickness and disability insurance funds are responsible for reimbursing
      health service benefits and paying disability benefits. The system's strength is
      that care is highly accessible and responsive to patients. However, the
      healthcare system's size remained relatively uncontrolled until recently, there
      is an excess supply of certain types of care, and there is a large number of
      small hospitals. The national government created a legal framework to modernize
      the insurance system to control budgetary deficits. Measures for reducing
      healthcare expenditures include regulating healthcare supply, healthcare
      evaluation, medical practice organization, and hospital budgets. The need to
      control healthcare facilities and quality of care in hospitals led to formal
      procedures for opening hospitals, acquiring expensive medical equipment, and
      developing highly specialized services. Reforms in payment and regulation are
      being considered. Health technology assessment (HTA) has played little part in
      the reforms so far. Belgium has no formal national program for HTA. The future of
      HTA in Belgium depends on a changing perception by providers and policy makers
      that health care needs a stronger scientific base.

PMID- 10932413
TI  - Health technology assessment in Denmark.
AB  - The Danish healthcare services are mainly provided by public sector institutions.
      The system is highly decentralized. The state has little direct influence on the
      provision of healthcare services. State influence is exercised through
      legislation and budget allocations. The main task of the state is to initiate,
      coordinate, and advise. Counties, which run the hospitals, also decide on the
      placement of services. The hospital sector is controlled within the framework of
      legislation and global budgets. General practitioners occupy a central position
      in the Danish healthcare sector, acting as gatekeepers to the rest of the system.
      The system works well, and its structure has resulted in steady costs of health
      care for a long period. There is no regulatory mechanism in the Danish health
      services requiring use of health technology assessment (HTA) as a basis for
      policy decisions, planning, or administrative procedures. However, since the late
      1970s a number of comprehensive assessments of health technology have formed the
      basis for national health policy decisions. In 1997, after years of public
      criticism of the quality of hospital care and health technologies, and on the
      basis of a previously developed national HTA strategy, a national institute for
      HTA (DIHTA) was established. There seems to be a growing awareness of evidence
      based healthcare among health professionals and a general acceptance of health
      economic analyses as a basis for health policy decision making. This progress is
      coupled with growing regional HTA activity in the health services. HTA seems to
      have a bright future in Denmark.

PMID- 10932414
TI  - Health technology assessment in Finland.
AB  - Finland has a long tradition of supporting social programs that promote equality
      and the welfare state. The healthcare system is financed mainly by taxation.
      Everyone is insured against illness. Each of Finland's five provinces is run by a
      provincial government that monitors the provision of social welfare and health
      care. However, the municipalities actually provide the services and regulate
      medical equipment and regionalization of services. During the early 1990s, gross
      domestic product (GDP) fell dramatically, and healthcare expenditure rose to 9.4%
      of GDP. Due to the economy's rapid recovery, the share of healthcare expenditure
      has again decreased and now matches the average level of OECD countries of
      approximately 7.7%. The former Finnish method of central planning and norm
      setting has guaranteed a fairly uniform development of necessary services
      throughout the country and free or low-cost access. Tight central planning did
      not, however, create incentives to contain costs. Therefore, in the beginning of
      the 1990s, decision-making power was largely decentralized to the municipalities,
      and the principles of state subsidies were reformed. In 1995, the Finnish Office
      for Health Care Technology Assessment (FinOHTA) was set up as a new unit of the
      National Research and Development Centre for Welfare and Health (STAKES). FinOHTA
      is intended to function as a national central body for advancing HTA-related work
      in Finland, with the ultimate goal of promoting the effectiveness and efficiency
      of Finnish health care. At present, the importance of HTA is widely recognized in
      Finland, especially in the face of rising healthcare costs.

PMID- 10932415
TI  - Health technology assessment in France.
AB  - The French healthcare system combines freedom of medical practice with nationwide
      social security. It is compulsory for every legal resident. A range of public and
      private institutions provide care, and patients have free access to physicians.
      The health coverage system is characterized by solidarity and universal
      responsibility. Although the French system is highly regulated, funding of health
      related expenses is a chronic social problem. Since the 1996 healthcare reform,
      the national objective for reimbursed healthcare expenditures is voted by the
      parliament, and the annual increase of hospital funding is controlled at the
      regional level. An agency for hospitals has been established in every region, and
      it quantifies needs indexes for future equipment and beds. However, establishing
      appropriate reference ratios based on objective assessment is difficult. The idea
      of basing policy and practice decisions on objective assessment grew for years,
      until the National Agency for the Development of Medical Evaluation was
      established in 1989. The 1996 healthcare reform expanded this agency to encompass
      hospital accreditation and renamed it the National Agency for Accreditation and
      Evaluation in Health. In March 1999, the National Agency for Health Products was
      established. It controls the safety of medical products and evaluates products'
      medical benefits before reimbursement decisions. Health technology assessment is
      now related to virtually every health policy process in France, and its role
      increases continually.

PMID- 10932416
TI  - Health technology assessment in Germany. Status, challenges, and development.
AB  - The objectives of this paper are to describe the status and development of health
      technology regulation with regard to coverage decisions and utilization, and to
      analyze the current situation of health technology assessment (HTA) in Germany.
      The relevant literature for controlling health technologies was identified by
      searching the literature and databases and through personal contacts. The
      literature was analyzed with regard to the different sectors in the healthcare
      system. For the analysis of the current state of HTA in Germany, a national
      survey was carried out. In addition, the names of topics under assessment were
      collected. The results show that coverage decisions in the ambulatory sector
      appear to be much more regulated than those in the inpatient sector. The same is
      true for diffusion and usage of technologies. The strict separation of the
      hospital and the ambulatory care sector in Germany constitutes a barrier to
      regulation and to making HTA an effective instrument in Germany. Until recently,
      HTA in Germany focused on biotechnology, such as gene technology. Recently the
      German Scientific Working Group of Technology Assessment in Health Care has
      adopted a systematic methodology to undertake HTAs. It can be concluded that
      regulation of health technologies in Germany is characterized by inconsistencies
      ranging from strict regulation in the ambulatory sector to almost no regulation
      in the rehabilitation sector. Increasing interest in HTA, in conjunction with a
      high priority assigned to evaluation of health technologies by the newly elected
      government, is likely to improve this situation in the future.

PMID- 10932417
TI  - Health technology assessment in Greece.
AB  - In 1983 a health reform aimed to assure universal coverage and equity in the
      distribution of services in Greece. The reform implied state responsibility for
      the financing and delivery of services and a reduction of the private sector. The
      model was a Bismarckian scheme for social insurance. However, healthcare delivery
      remains fragmented and uncoordinated and the private sector is getting stronger.
      The dominant payment system is fee-for-service for the private sector and
      administered prices and salaries for public hospitals and social insurance funds.
      The many insurers have their own eligibility requirements, validation procedures,
      etc. Coverage of services by social security funds, probably among the most
      comprehensive in Europe, is determined more on historical and political grounds
      than on efficiency or cost-effectiveness. The system is plagued by problems,
      including geographical inequalities, overcentralization, bureaucratic management,
      poor incentives in the public sector, open-ended financing, inefficient use of
      hospital beds, and lack of cost-effectiveness. There are no specific legal
      provisions for the control of health technology. Technologies are introduced
      without standards or formal consideration of needs. There are no current efforts
      to control health technology in Greece. However, health technology assessment
      (HTA) has gained increasing visibility. In 1997 a law provided for a new
      government agency responsible for quality control, economic evaluation of health
      services, and HTA. The hope is that the new law may introduce evaluation and
      assessment elements into health policy formulation and assure that cost
      effectiveness, quality, and appropriate use of health technology will receive
      more attention.

PMID- 10932418
TI  - Health technology assessment in Ireland.
AB  - Ireland's health system is primarily funded from general taxation and is publicly
      provided, although private health care retains a considerable role. It is a
      unique structure, a mixture of universal health service free at the point of
      consumption and a fee-based private system where individuals subscribe to private
      health insurance that covers some of their medical expenses. The recent history
      of the Irish health services saw consolidation of existing services and an
      expansion into new areas to adapt to changing practices and needs. There has also
      been a drive to extract maximum efficiency so as to maintain the volume and
      quality of patient services at a time of very tight financial constraints.
      Introduction of new health technologies continued to accelerate. New technologies
      tended to spread rapidly before systematic appraisal of their costs and benefits.
      When the state is involved in funding the public hospital system, acceptance of
      new technology is a matter for discussion between agencies and the Department of
      Health and Children. Decisions about spending annual "development funding" have
      generally not been based on careful assessment of proposals for new technology.
      In 1995, a healthcare reform put new Public Health Departments in Health Boards
      in a prime position in Ireland's health services organization. These departments
      now emphasize evidence-based medicine. While Ireland does not have a national
      health technology assessment (HTA) program, there are plans to form an advisory
      group on HTA in 1998. HTA is seen as a significant element of future health
      policy in Ireland.

PMID- 10932419
TI  - Health technology assessment in Italy.
AB  - Italy has a national health service (SSN) dating to 1978. Italy's system of
      government is characterized by a rather high degree of decentralization of power,
      and the health system is likewise decentralized. Most of the responsibilities for
      health care have been ceded to the regions. The state retains only limited
      coordinating and supervisory powers. The state has a financial responsibility for
      the national health service, but state contributions are limited and expenditures
      in excess of this made by the region must be financed from other sources. Health
      reforms of 1992-93 aimed at making the regions more sensitive to the need to
      control aggregate expenditure and to monitor measures to promote efficiency,
      quality, and citizen-patient satisfaction. The diffusion of individual health
      technologies has been relatively uncontrolled in many regions in Italy, although
      tight central constraints on capital spending have contained diffusion of new
      technology. Regulation of placement of services is a planning function and is the
      responsibility of both the Ministry of Health and the regions. Health technology
      assessment (HTA) activities have been expanding since the early 1990s, but these
      activities tend to be untargeted, uncoordinated, and without priorities.
      Nonetheless, the principal actors in the SSN at national, regional, and local
      levels are becoming more sensitive to the need to apply criteria of clinical and
      cost-effectiveness and to be more rigorous in deciding what services to
      guarantee. There are reasons to be guardedly optimistic about the future of HTA
      in Italy.

PMID- 10932420
TI  - Health technology assessment in Luxembourg.
AB  - Luxembourg's public health insurance is a compulsory insurance for all employees,
      self-employed professionals, farmers, and pensioners. It is financed through
      contributions of the insured people, as well as by state taxes. Providers of
      health care are mainly private nonprofit institutions and self-employed
      professionals. All healthcare procedures are defined in fee schedules determined
      by a common decision of the Ministers of Social Security and Health according to
      proposals of a board of experts. The relative value of a service is also
      determined by the corresponding fee schedule. Hospitals are financed by
      individual budgets negotiated between each hospital and the health insurance.
      These hospital budgets do not cover services provided in hospitals by medical
      specialists, who are reimbursed on a fee-for-service basis. A low on hospital
      planning and organization allows the government to restrict the installation in
      hospitals of very expensive equipment or of equipment for which there is only a
      limited need in Luxembourg hospitals. Until recently there has been limited
      interest in or use of health technology assessment (HTA). However, large hospital
      investments have provoked some interest in the last few years. The Ministry of
      Health has asked for some HTA studies when a concrete decision had to be taken.
      Luxembourg decision makers have become more aware that HTA may help them to
      become more informed about the short- and long-term consequences of the
      application of health technology.

PMID- 10932421
TI  - Health technology assessment in The Netherlands.
AB  - The Dutch healthcare system is not a single overall plan, but has evolved from a
      constantly changing mix of institutions, regulations, and responsibilities. The
      resulting system provides high-quality care with reasonable efficiency and equal
      distribution over the population. Every Dutch citizen is entitled to health care.
      Health insurance is provided by a mix of compulsory national insurance and public
      and private insurance schemes. Hospitals generally have a private legal basis but
      are heavily regulated. Supraregional planning of high-tech medical services is
      also regulated. Hospitals function under fixed, prospective budgets with
      regulation of capital investments. Independent general practitioners serve a
      gatekeeper role for specialist and hospital services and are paid by capitation
      or fee for service. Specialists are paid by fee for service. All physicians' fees
      are controlled by the Ministry of Economic Affairs. Coverage of benefits is an
      important method of controlling the cost of services. There is increasing concern
      about health care quality. Health technology assessment (HTA) has become
      increasingly visible during the last 15 years. A special national fund for HTA,
      set up in 1988, has led to many formal and informal changes. HTA has evolved from
      a research activity into policy research for improving health care on the
      national level. In 1993 the government stated formally that enhancing
      effectiveness in health care was one of its prime targets and that HTA would be a
      prime tool for this purpose. The most important current issue is coordination of
      HTA activities, which is now undertaken by a new platform representing the
      important actors in health care and HTA.

PMID- 10932422
TI  - Health technology assessment in Portugal.
AB  - The Portuguese healthcare system is often portrayed as a National Health Service
      (NHS) model, characterized by universal coverage, comprehensive benefits, nearly
      free services, national tax financing, and public ownership or control of the
      factors of production. However, in reality the system fails to accomplish these
      features in a complete way. There coexist a number of occupation-related health
      insurance schemes that were originally intended to be integrated into the NHS. In
      addition, in key areas the NHS does not provide the wide range of services it
      promises. The public sector has a predominant role in the provision of hospital
      stays and general practitioner consultations, but the private sector provides a
      major portion of specialist consultations, dental consultations, and diagnostic
      services. Major problems in the system led to health reforms in the 1990s. New
      reform proposals include some specific steps concerning health technology,
      including standards for medical equipment based on quality, geographic
      distribution, sustainability, and cost-effectiveness. A new National Plan of
      Health Equipment was completed in 1998, aimed at improving the distribution of
      equipment. Despite reforms, healthcare expenditures continue to rise. There is
      general agreement that gains in efficiency could be made. This situation is
      beginning to encourage interest in health technology assessment (HTA) in
      Portugal, although these activities are not yet very developed. Recently,
      legislation requiring presentation of economic evaluations for new pharmaceutical
      products was enacted. Present plans also call for the creation in the future of a
      national agency for HTA.

PMID- 10932423
TI  - Health technology assessment in Spain.
AB  - The Spanish Constitution of 1978 established a healthcare system available to
      everyone and free at the point of service. The General Health Law of 1986 also
      established the framework for a National Health System (NHS). The Constitution
      and the law form the regulatory framework for the devolution of healthcare
      services to the Autonomous Regions. All the 17 Autonomous Regions have complete
      power regarding public health and planning. However, responsibilities on
      healthcare financing, organization, provision, and management have devolved to
      only seven Autonomous Regions. Financial support for health services comes mostly
      from taxes. Global budgets are a mechanism used by hospitals to control the
      acquisition of medium and low health technology. Major capital investments for
      health technology are controlled by the central government in 10 Autonomous
      Regions (population coverage of 38%) and by the Regional Health Services in the
      seven remaining Autonomous Regions. In 1995 a regulation for basing the
      introduction of new procedures and medical equipment on the assessment of safety,
      efficacy, and efficiency was issued. Health technology assessment (HTA) has a
      long history in Spain, beginning with the Advisory Board on High Technology in
      the government of Catalonia in 1984. This board evolved into the Catalan Agency
      for HTA (CAHTA) in 1994. The Basque Country established a unit for HTA in 1992
      (Osteba) and the Andalusian government created an agency in 1996 (AETSA). A
      national agency for HTA (AETS) was established in 1994. These different programs
      coordinate their work and together act as an Advisory Committee of the
      Interregional Council of the NHS.

PMID- 10932424
TI  - Health technology assessment in Sweden.
AB  - Sweden has a welfare system that is based on the fundamental principle that all
      citizens are entitled to good health and medical care, regardless of where they
      live or what their economic circumstances are. Health and medical care are
      considered to be public sector responsibilities. However, there is growing
      interest in establishing more private alternatives to public care. An important
      characteristic of the Swedish healthcare system is its decentralization, with a
      major role for county councils. County councils are now merging into larger
      administrative units (region). The whole Swedish system is in the process of
      reform, mainly because of perceptions that it was too rigid and had insufficient
      patient orientation. An important factor in the reforms is that power in the
      system will be even more decentralized and will have greater public input. This
      change is seen as calling for increased central follow-up and evaluation of
      matters such as social, ethical, and economic aspects. Although the state has
      decentralized control, it still attempts to control the general direction of the
      system through regulation, subsidy, recommendations, and guidelines. An important
      actor in the system is the Swedish Council on Technology Assessment in Health
      Care (SBU). SBU began in 1987 with assessments of health technologies, but its
      success has recently led policy makers to extend its coverage to dental care.
      Health technology assessment is increasingly visible to policy makers, who find
      it useful in decision making.

PMID- 10932425
TI  - Health technology assessment in Switzerland.
AB  - Switzerland has a mixed public and private healthcare system. All citizens are
      enrolled in compulsory basic health insurance. A 1996 law allows people to choose
      among different sickness funds and managed care plans. The federal government is
      empowered to act on important health issues, but the 26 cantons have prime
      responsibility in health care and social welfare. They have their own laws on
      health care, hygiene, hospitals, and social welfare. These laws are not
      harmonized. The system is complex, with a mix of public (mainly hospitals) and
      private (mainly doctors' offices) providers. The health services are
      decentralized. Ambulatory care was traditionally provided in doctors' offices,
      but the last decade has seen the development of centers for day surgery, group
      practices, and managed care plans. Decisions on placement, location, and
      extension of services are decentralized. The payment system is very complex.
      Current trends include global budgets, cost analyses, and prices related to
      patient categories. However, coverage policy is developed centrally and includes
      both traditionally established services and new technologies. New technologies
      are added to the list only after evaluation by the Federal Coverage Committee.
      The coverage process integrates health technology assessment (HTA). Coverage can
      be granted in stages, including limited coverage and temporary coverage.
      Technologies and coverage can be reevaluated on the basis of registries or
      assessment information. The structure of the Swiss healthcare system does not
      lend itself to the establishment of a national HTA program. However, recent moves
      include the development of a coordinating mechanism for HTA in Switzerland.

PMID- 10932426
TI  - Health technology assessment in the United Kingdom.
AB  - The National Health Service (NHS) provides universal health coverage for all
      British citizens. Most services are free of charge, although modest copayments
      are sometimes applied. About 11% of the population also has private insurance.
      General practitioners, generally the first point of contact for accessing the
      system, are independent contractors who serve as gatekeepers for specialist and
      hospital services and enjoy substantial clinical autonomy. Hospitals are public
      and are regionalized, but the 1990 reforms made them self-governing trusts that
      contract with local purchasers (health authorities and general practitioner
      fundholders). Reforms beginning in 1990 moved the NHS away from a centralized
      administrative structure to more pluralistic arrangements in which competition,
      as well as management, influences how services develop. Health technology and
      health technology assessment (HTA) have gained increasing attention in the NHS
      during this period, as part of a wider NHS Research and Development (R&D)
      Strategy. The strategy promotes a knowledge-based health service with a strong
      research infrastructure and the capacity to critically review its own needs. HTA
      is the largest and most developed of the programs within the strategy. It has a
      formal system for setting assessment priorities involving widespread consultation
      within the NHS, and a National Co-ordinating Centre for Health Technology
      Assessment. The strategy supports related centers such as the U.K. Cochrane
      Centre and the NHS Centre for Reviews and Dissemination. A hallmark of the HTA
      program is strong public participation. The United Kingdom has made a major
      commitment to HTA and to seeking effective means of reviewing and disseminating
      evidence.

PMID- 10932427
TI  - Health technology assessment and health care in the European Union.
AB  - The papers on the 16 European countries presented in this issue show their great
      diversity of health systems. Health technology assessment (HTA) has been
      institutionalized in a number of members of the European Union and has a growing
      impact on health policy. A remaining challenge is to see HTA visible and useful
      at the European level, which requires more active coordination of national and
      regional activities. A network of HTA programs and researchers has been
      established. The HTA-Europe Steering Committee has suggested a number of actions
      by the European Commission to promote further coordination. The most important
      conclusion of the HTA-Europe report is that a permanent coordinating structure is
      needed at the European level.

PMID- 10932428
TI  - Health technology assessment in Europe. Improving clarity and performance.
AB  - This paper discusses the challenges facing health technology assessment (HTA) in
      Europe, based on an explicit analysis of the characteristics of an "optimal" HTA
      system. It has three objectives: a) to elaborate an explicit system of policy
      goals and the characteristics of an optimal HTA system that facilitates the
      achievement of these goals; b) to identify the general institutional incentive
      barriers (government and market failures) that prevent the attainment of an
      optimal HTA system in Europe; and c) to argue that evaluation of the implications
      of health technologies for equity and inequality in health is an essential part
      of this optimal system and a considerable challenge for HTA decision makers,
      especially as national governments realign policy toward equity goals.

PMID- 10932429
TI  - The use and impact of rapid health technology assessments.
AB  - OBJECTIVES: To consider the impact of rapid health technology assessments
      undertaken as part of a program in a provincial healthcare system in response to
      urgent requests for advice. METHODS: Review of the development and preparation of
      20 rapid assessment reports, communication with decision makers within the
      healthcare system, and appraisal of data subsequent to preparation of the
      reports. RESULTS: Fourteen of the assessments were judged to have had an
      influence on policy and other decisions, as judged by responses from those who
      had requested advice. Another four were considered to have provided guidance,
      while having less immediate influence on decisions, and two others had no
      apparent impact. Quality of the assessments was considered acceptable, on the
      basis of literature that subsequently became available and from comments
      received. CONCLUSIONS: These brief reports are considered to be a useful
      component of a health technology assessment program. However, they should be
      regarded as provisional appraisals and followed up with more detailed evaluation
      where possible.

PMID- 10932430
TI  - Is there bias in the publication of individual patient data meta-analyses?
AB  - OBJECTIVE: There is increasing empirical evidence for the existence of bias in
      the publication of primary clinical research, with statistically significant
      results being published more readily, more quickly, and in higher impact
      journals. Meta-analysis of individual patient data (IPD) may represent a gold
      standard of "secondary" clinical research, giving the best possible summary of
      current evidence for a particular question, but publication of these may also be
      subject to bias. This study aimed to explore which factors might be associated
      with publication of IPD meta-analyses and to identify potential sources of bias.
      METHODS: For all known IPD meta-analysis projects in cancer, the responsible
      investigator was surveyed by means of a questionnaire to determine descriptive
      characteristics of the meta-analysis, the nature of the results, and details of
      the publication history. RESULTS: There is no good evidence that overall
      publication status of meta-analyses in cancer is dependent on the statistical or
      clinical significance of the results. However, those meta-analyses with
      nonsignificant results did seem to take longer to publish and were published in
      lower impact journals compared with those with more striking results.
      CONCLUSIONS: Based on the current data, there seems to be no strong association
      between the results of IPD meta-analyses in cancer and publication.

PMID- 10932431
TI  - Identifying studies for systematic reviews. An example from medical imaging.
AB  - OBJECTIVES: To determine if published figures on the proportion of articles
      included in systematic reviews and identified in electronic databases are
      applicable to an example from medical imaging. METHODS: A systematic review was
      performed. Additionally, sensitivity and precision of a MEDLINE search were
      compared with values from three published searches, each customized for a
      specific field. RESULTS: All articles included in the systematic review were in
      electronic databases. The MEDLINE search had low precision compared with searches
      in other fields. CONCLUSIONS: In a specific area of medical imaging, electronic
      databases, including MEDLINE, are reliable sources of articles.

PMID- 10932432
TI  - Preoperative evaluation in elective surgery. INAHTA synthesis report.
AB  - OBJECTIVES: To collect and summarize information published by INAHTA agencies on
      the indications, habitual attitudes and practices, and economic and legal
      implications of preoperative evaluation in elective surgeries. METHOD: The
      authors appraised the information contained in six papers published between 1989
      and 1999 in Sweden, France, Basque Country, the Netherlands, United Kingdom, and
      Catalonia. The section on indications in preoperative evaluation does not present
      global conclusions. The sections addressing habitual attitudes and practices
      among physicians and those addressing economic and legal considerations cover
      only the similarities among the reports and the main ideas relating to these
      issues. RESULTS: The conclusions found in the reports about indications in
      preoperative evaluation are similar or differ slightly, e.g., as regards age
      limits in patients for whom the tests are recommended. However, more important
      differences are shown in other areas, especially in reports where consensus
      methods were used. In some instances, the opinions, attitudes, and customary
      practices of professionals during the preoperative stage do not concur with the
      recommendations extracted from the assessment reports and the customary practice
      of doctors. In relation to economic considerations, a substantial quantity of
      resources could be liberated if the recommended general clinical practices were
      followed. From the point of view of civil law, the evidence-based recommendations
      could be considered as a kind of coded lex artis.

PMID- 10932434
TI  - Do QOL instruments agree? A comparison of the 15D (Health-Related Quality of
      Life) and NHP (Nottingham Health Profile) in hip and knee replacements.
AB  - OBJECTIVES: Several instruments for measuring health-related quality of life
      (HRQOL) have been developed, and others are under construction. The problem is
      whether the different HRQOL measures show comparable results. We first compared
      the functional relationship of the Nottingham Health Profile (NHP) and the 15
      dimensional measure of HRQOL (15D) in hip and knee replacement patients. The
      hypothesis was that condition or intervention does not affect the functional
      relationship between NHP and 15D changes. METHODS: We assessed the agreement of
      the instruments by comparing observed changes in the 15D and its fitted values
      derived by regressing the 15D by the NHP dimensions. Patients (n = 452) were
      recruited consecutively from seven Finnish orthopedic departments during April
      1991-May 1992. HRQOL was measured prior to surgery and 6, 12, and 24 months
      postoperatively. RESULTS: There was a different functional relationship between
      the HRQOL instruments in hip and knee patients; they agreed upon the direction of
      changes in HRQOL in 84% and showed opposite signs in 12%. The NHP showed
      significantly more improvement in quality of life than the 15D. CONCLUSIONS: The
      two instruments were in slight but significant disagreement. Estimates of
      effectiveness can vary according to the instrument used. Comparisons of
      effectiveness in healthcare programs measured by differing instruments need
      information on the functional discrepancies between the instruments in the
      conditions and interventions in which they are applied.

PMID- 10932433
TI  - A comparison of the cost-effectiveness of stroke care provided in London and
      Copenhagen.
AB  - OBJECTIVES: This study compared the relative cost-effectiveness of stroke care
      provided in London and Copenhagen. METHODS: Hospitalized stroke patients at
      centers in London (1995-96) and Copenhagen (1994-95) were included. Each
      patient's use of hospital and community health services was recorded for 1 year
      after stroke. Center-specific unit costs were collected and converted into
      dollars using the Purchasing Power Parity Index. An incremental cost
      effectiveness ratio (ICER) was calculated comparing a Copenhagen model of stroke
      care to a London model, using regression analysis to adjust for case-mix
      differences. RESULTS: A total of 625 patients (297 in Copenhagen, 328 in London)
      were included in the analysis. Most patients in London (85%) were admitted to
      general medical wards, with 26% subsequently transferred to a stroke unit. In
      Copenhagen, 57% of patients were directly admitted to a stroke or neurology unit,
      with 23% then transferred to a separate rehabilitation hospital. The average
      length of total hospital stay was 11 days longer in Copenhagen. Patients in
      Copenhagen were less likely to die than those in London; for patients with
      cerebral infarction the hazard ratio after case-mix adjustment was 0.53 (95% CI
      from 0.35 to 0.80). However, a lower proportion of patients with hemorrhagic
      stroke died in London. The ICER of using the Copenhagen compared with the London
      model of care ranged from $21,579 to $37,444 per life-year gained for patients
      with cerebral infarctions. CONCLUSIONS: The ICERs of the Copenhagen compared with
      the London model of care were within a range generally regarded as cost
      effective.

PMID- 10932436
TI  - Incorporating data from dissertations in systematic reviews.
AB  - OBJECTIVES: To determine whether unpublished dissertations are an important
      source of trials for systematic reviews. METHODS: In a review of infant massage,
      we identified 17 dissertations. We recorded whether each dissertation was
      included in the review and, if so, whether it contributed data to any analyses.
      RESULTS: Thirteen dissertations were excluded, 11 because of poor reporting of
      methodology. Three dissertations were also published as journal papers. The data
      from the remaining dissertation were not included in any analysis. Reviewing data
      on the Cochrane Library, only one of 878 reviews included data from a
      dissertation that might have changed a review's conclusions. CONCLUSIONS:
      Searching for and retrieving unpublished dissertations involves considerable time
      and effort and appears to influence the conclusions of a review only rarely.

PMID- 10932435
TI  - Willingness to pay in treatment of bleeding disorders.
AB  - This paper presents the results of a contingent valuation study measuring
      willingness to pay (WTP) for treatment of patients with von Willebrand's disease.
      Median WTP for treatment of this disorder was $1,500 or $3,500, depending on how
      the initial bid was structured. Regression analysis shows that income, education,
      and a category rating scale for health status were significant in predicting WTP.
      The adjusted annual WTP was $2,178. WTP surveys may increasingly be useful for
      health technology assessment. Starting point bias in how the bids are structured
      must be recognized.

PMID- 10932437
TI  - Reports from the Swedish Council on Technology Assessment in Health Care (SBU).
      The patient-doctor relationship.

PMID- 10932438
TI  - Reports from the Swedish Council on Technology Assessment in Health Care (SBU).
      Urinary incontinence.

PMID- 10932439
TI  - Detoxification centers: who's in the revolving door?
AB  - Data from 443,812 admissions to publicly funded detoxification centers in
      Massachusetts (fiscal year 1984 to fiscal year 1996) were analyzed to assess
      changes in the population served. Substantial increases in admissions of women,
      African Americans, and Hispanics were apparent. Mean age at admission declined
      and unemployment increased. A 25% decline in admissions reporting alcohol use was
      coupled with a twofold increase in reported cocaine use and a fourfold increase
      in heroin use. Detoxification services have evolved. The older, white, male
      alcoholic is no longer the primary consumer. Policy initiatives (e.g., increased
      services for women) and the changing epidemiology of drugs abuse (e.g., increased
      access to heroin) contributed to the changing population served in detoxification
      centers.

PMID- 10932440
TI  - Client typology based on functioning across domains using the CAFAS: implications
      for service planning.
AB  - Cluster analysis was used to develop a five-group typology based on the eight
      subscales of the Child and Adolescent Functional Assessment Scale (CAFAS) using
      data on 4,758 youths referred to Community Mental Health Service Providers in
      Michigan. The groups are described in terms of clinical diagnoses, overall
      impairment in functioning, past and current use of services from other agencies
      (i.e., juvenile justice, social services), and caregiver resourcefulness. From
      most to least impaired, the clusters were the following: Substance
      Users/Externalizers, Comorbid/Self-Harmful, Delinquents, Marked/School Problems,
      and Adjustment Problems with Impairment/Secondary Prevention. The results are
      being used to help identify the most impaired youths with serious emotional
      disturbance (SED) youths, develop specific programs and services for the
      different types of youths being served, determine staff training needs, and
      foster clinical practice in which the youth's progress is continually monitored.

PMID- 10932441
TI  - Help-seeking steps and service use for children in foster care.
AB  - This study describes help-seeking steps and service-use patterns for school-age
      children in foster care. It also examines how these access indices are moderated
      by sociodemographic, enabling, and child disorder factors. Two home interviews
      and a telephone teacher interview were conducted using a sample of 302 randomly
      selected children (age 6-12 years) in foster care. The majority of children (80%)
      were given a psychiatric diagnosis, and 43% of the foster parents perceived a
      need for mental health services for the child. In the past year, about one-half
      of the children had received mental health (51%) and special education services
      (52%). Age and ethnicity, foster parent education, placement history, level of
      monthly benefits, number of caseworker visits, and disorder characteristics were
      related to help-seeking steps and mental health service use. Strategies to
      improve access to mental health services for children in foster care should
      include interventions at the caregiver and system levels.

PMID- 10932442
TI  - Longitudinal effects of integrated treatment on alcohol use for persons with
      serious mental illness and substance use disorders.
AB  - A randomized experimental design was used to assign participants to an integrated
      mental health and substance use treatment program or to standard hospital
      treatment. A multilevel, nonlinear model was used to estimate hospital treatment
      effects on days of alcohol use for persons with serious mental illness and
      substance use disorders over 18 months. The integrated treatment program had a
      significant effect on the rate of alcohol use at 2 months postdischarge, reducing
      the rate of use by 54%. Motivation for sobriety at hospital discharge,
      posttreatment self-help attendance, and social support for sobriety were also
      found to reduce the rate of use during the follow-up period. Implications for
      mental health treatment and aftercare support are discussed.

PMID- 10932443
TI  - Issues and outcomes in integrated treatment programs for dual disorders.
AB  - In an integrated, dual disorder treatment program delivered at two sites, the
      authors address numerous barriers to delivering services to dually diagnosed
      consumers and employ a set of multidimensional indicators to assess outcome.
      Consumers who received services through the well-implemented, integrated services
      program for 12 months were functioning better in the community. There was a cost
      shifting from mental health to drug and alcohol services, as well as a one-third
      increase in the total costs of care by the end of the first year of treatment.
      Program implementation issues are described and the clinical management
      implications for more effectively serving dually diagnosed consumers through
      integrated treatment programs are discussed.

PMID- 10932444
TI  - The American Red Cross disaster mental health services: development of a
      cooperative, single function, multidisciplinary service model.
AB  - Not until 1989 did the Red Cross officially recognize a need for a systematic and
      organized plan for the mental health needs of disaster survivors. Over the next
      decade, the Red Cross Disaster Mental Health Services program has developed and
      evolved to assist both disaster victims and the Red Cross workers who serve them
      to cope with the overwhelming stresses encountered by both groups in the
      aftermath of disasters. The Red Cross now coordinates a large and diverse group
      of mental health professionals from fields of psychology, psychiatry, nursing,
      social work, marriage and family therapy, and counseling who work together
      cooperatively. Cross-disciplinary conflicts are minimized by the Red Cross'
      generic approach to the various mental health professional specialties as
      functionally interchangeable in performing Red Cross duties. This article reviews
      the development of this process and describes one local Red Cross chapter's early
      experience as part of this effort.

PMID- 10932445
TI  - Identifying clinical competencies that support rehabilitation and empowerment in
      individuals with severe mental illness.
AB  - Individuals with severe mental illness often do not receive appropriate treatment
      or rehabilitation. One approach to improving their care begins by identifying
      competencies that clinicians should possess. This project developed a set of core
      clinical competencies that pertain to community-based care and support the goals
      of empowerment and rehabilitation. Development of the competency set began with
      review of existing literature and competency statements, and focus groups and
      interviews with clients, family members, clinicians, managers, experts, and
      advocates. Representatives from each of these groups participated in a national
      panel and used a structured process to identify 37 final competencies. Panel
      members agreed that these competencies are very important in determining outcomes
      and often are not present in current clinicians. This project demonstrates that
      it is possible to develop a core competency set that can be strongly supported by
      diverse groups of stakeholders. These competencies may be useful in clinician
      training, recruitment, and credentialing efforts.

PMID- 10932446
TI  - Large employers' selection criteria in purchasing behavioral health benefits.
AB  - To determine the criteria other than cost large employers use in selecting and
      monitoring behavioral health benefits, this study interviewed 31 of 44 (70.4%)
      randomly selected corporations employing at least 5,000 workers. While more than
      60% of employers considered administrative efficiency and provider access to be
      very influential in their selection of behavioral health benefits, only 12.9%
      (95% confidence interval 0.7%-25.1%) considered clinical outcomes. Employers who
      considered clinical outcomes in their purchasing decision reported significantly
      greater satisfaction with the quality and cost of their behavioral health
      benefits. Following selection, 38.7% of corporations used employee complaints to
      monitor quality problems in their behavioral health benefits; 3.2% used clinical
      outcomes. If society expects employers to purchase behavioral health care on the
      basis of quality as well as cost, more employers need better indicators of
      quality.

PMID- 10932448
TI  - HIV-related services for persons with severe mental illness: policy and practice
      in New Hampshire community mental health.
AB  - Rates of HIV and HIV risk behaviors are elevated among people with severe mental
      illnesses (SMI). Little is known about the extent to which community mental
      health (CMH) centers screen, refer, and educate their clients regarding HIV and
      sexually transmitted diseases (STDs). The authors surveyed CMH administrators and
      clinicians in New Hampshire regarding HIV/STD policy, practices, knowledge, and
      attitudes. HIV/STD service availability varied, and the amount of services
      provided was unrelated to the prevalence of HIV and AIDS in that region.
      Clinicians were knowledgeable about general HIV information but lacked specific
      knowledge about HIV related to persons with SMI. CMH staff had positive attitudes
      about helping clients with HIV issues. Administrators were interested in
      receiving training. Policy leadership, CMH practice guidelines, and training are
      warranted in light of the pressing public health implications of HIV/STDs among
      people with SMI.

PMID- 10932449
TI  - Successful temporary nonsmoker?

PMID- 10932447
TI  - Predictors of patient entry into alcohol treatment after initial diagnosis.
AB  - To improve the quality of care for alcohol-related disorders, key transitions in
      the continuum of care, including treatment entry, must be fully understood. The
      purpose of this study was to investigate identifiable predictors of patient entry
      into a substance-use treatment program following the initial diagnosis of an
      alcohol-related disorder on a medical or surgical inpatient unit. An
      administrative computerized database was used to identify the sample for this
      study. Inpatient and outpatient records were obtained from the Little Rock
      VAMC/DHCP. Predictors of patient entry into treatment within six months of the
      initial diagnosis of an alcohol related disorder included age younger than than
      60 (odds ratio [OR] = 4.6), not married (OR = 1.7), primary diagnosis of an
      alcohol-related disorder (OR = 7.7), diagnosis of a comorbid drug (OR = 4.3) or
      psychiatric disorder (OR = 3.6), diagnosis by a medical as opposed to a surgical
      specialty (OR = 6.0), and African American (OR = 1.7).

PMID- 10932450
TI  - Let's roll up our sleeves and get the job done.

PMID- 10932451
TI  - The World Wide Web: where is it taking APhA?

PMID- 10932452
TI  - American Pharmaceutical Education, 1852-1902.

PMID- 10932453
TI  - DUR: good systems provide assistance, not annoyance.

PMID- 10932454
TI  - The chase is on (and I'm mad as hell).

PMID- 10932455
TI  - APhA drug treatment protocols: management of foot ulcers in patients with
      diabetes.

PMID- 10932456
TI  - Optimizing adherence to pharmaceutical care plans.
AB  - Adherence to pharmacotherapy is essential to optimal therapeutic outcomes. The
      pivotal role of the pharmacist in optimizing adherence encompasses many actions:
      assessing the adherence problem, identifying predisposing factors, providing
      comprehensive counseling, and recommending specific adherence strategies targeted
      to the patient's needs. Patients who have chronic conditions, physical or
      cognitive impairments, or cultural backgrounds outside the mainstream may have
      special needs that should be addressed in the adherence plan. Pharmaceutical care
      plans also should take into account the patient's age, stage of life, and
      literacy level. Although a wide range of adherence aids and strategies are
      available, the key to success is to tailor the intervention to the individual
      patient and, when necessary, to combine interventions to optimize adherence.

PMID- 10932457
TI  - Pharmacists' readiness to assess consumers' over-the-counter product selections.
AB  - OBJECTIVE: To measure and explain pharmacists' readiness to adopt a proposed new
      standard for assessing consumers' over-the-counter product selections. DESIGN:
      Cross-sectional, descriptive study based on the theoretical underpinnings of the
      Transtheoretical Model of Change. A questionnaire was used for data collection.
      Sections included: (1) pharmacists' readiness to engage in a proposed standard of
      practice; (2) the positive and negative aspects of doing so; (3) pharmacists'
      agreement with current legislative status of pharmacist-only products; and (4)
      demographics. SETTING: Community pharmacy. PARTICIPANTS: Community pharmacists in
      one Canadian province. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Pharmacists' readiness to adopt a proposed new standard of care. RESULTS:
      Response rate was 70.6%. Most respondents were staff pharmacists in independent
      pharmacies. The majority were not ready to adopt the proposed new behavior--57.6%
      were in the precontemplation stage. Age, sex, year of graduation, workload, and
      size of town/city had no significant effect on readiness for change. As expected,
      precontemplators showed less overall support for keeping pharmacist-only agents
      behind the counter. Positive and negative beliefs about the proposed standard
      varied across stages. CONCLUSION: Any initiatives to increase pharmacist
      involvement in assessing consumer nonprescription product selections must
      acknowledge that pharmacists differ in their degree of readiness for change.

PMID- 10932458
TI  - Drug utilization review of sedative/hypnotic agents in Texas Medicaid patients.
      Texas Medicaid Vendor Drug Program Drug Utilization Review Board.
AB  - OBJECTIVE: To assess use of sedative/hypnotic agents in Texas Medicaid patients
      and evaluate practitioner receptiveness to intervention letters concerning
      sedative/hypnotic prescribing generated by the Texas Medicaid Drug Utilization
      Review (DUR) Board. DESIGN: Retrospective DUR. SETTING: Texas Medicaid
      retrospective DUR program. PATIENTS OR OTHER PARTICIPANTS: 244 Texas Medicaid
      patients and 291 Texas physicians. INTERVENTION: Patient profiles for Texas
      Medicaid patients were reviewed retrospectively to quantify sedative/hypnotic
      prescribing practices. Intervention letters were prepared and sent to physicians
      directly involved in the care of patients receiving excessive sedative/hypnotic
      therapy. Physician responses were categorized based on information presented in
      the intervention letter and circumstances surrounding the identified patient.
      Prescribing practices were assessed approximately 1 year after the intervention
      to determine the impact of intervention letters on prescribing. MAIN OUTCOME
      MEASURE: Physician response to intervention letter. RESULTS: Responses were
      received from 208 of 291 physicians (71.5%). Approximately 40% of physicians
      agreed in principle with the suggestions offered by the Texas Medicaid DUR Board
      to minimize chronic sedative/hypnotic use. Almost one-half of these physicians
      had discontinued sedative/hypnotic therapy for the identified patients 1 year
      after the intervention. Approximately 9% justified continued sedative/hypnotic
      use based on patient diagnosis or refractory response to treatment, and 55
      physicians (26.4%) were unwilling to alter therapy because of patient-specific
      factors. CONCLUSION: Through the use of retrospective DUR, Texas Medicaid
      patients receiving excessive amounts of sedative/hypnotic agents were identified
      and improvements in sedative/hypnotic therapy were initiated. DUR can be useful
      not only in identifying problem areas, but also in encouraging physicians to
      modify prescribing practices through educational means.

PMID- 10932459
TI  - Effect of patient information on the quality of pharmacists' drug use review
      decisions.
AB  - OBJECTIVE: To evaluate the effect of incremental increases in patient information
      on the quality of pharmacists' clinical decisions related to legally mandated
      prospective drug utilization review (DUR) responsibilities. DESIGN: Unblinded
      comparison of two groups. PARTICIPANTS: 28 community pharmacists in Indiana
      (group 1) and 32 Public Health Service pharmacists employed in the Indian Health
      Service (IHS) (group 2). INTERVENTIONS: Clinical cases involving prescribing
      problems were developed from patient charts. Each case contained four levels of
      increasing patient information: Level 1 included only information required for a
      legal prescription in Indiana; Level 2 added the patient's current medication
      profile, age, and allergies; Level 3 added the diagnosis or reason for use of the
      prescribed medication; and Level 4 added the physician's progress note.
      Pharmacists were asked to evaluate the prescribed drug therapy at each level of
      each case and complete a Dispensing Appropriateness Index (DAI) report, which
      included all prospective DUR criteria required by the Omnibus Budget
      Reconciliation Act of 1990. The quality of pharmacists' DUR decisions at each
      level of patient information was evaluated by comparing pharmacists' responses on
      the DAI reports with the consensus judgment of two clinical experts. RESULTS: The
      quality of both community and IHS pharmacists' DUR decisions improved
      significantly at each incremental level of patient information. CONCLUSION:
      Pharmacists in this study made better decisions when they had access to more
      complete patient information on which to base their decisions.

PMID- 10932460
TI  - Compatibility and stability of linezolid injection admixed with three
      cephalosporin antibiotics.
AB  - OBJECTIVE: To evaluate the physical compatibility and chemical stability of
      linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram,
      ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and
      23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory.
      INTERVENTIONS: The test samples were prepared by adding the required amount of
      the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL. MAIN
      OUTCOME MEASURES: Physical stability and chemical stability based on drug
      concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C
      and 23 degrees C protected from light. RESULTS: All of the linezolid admixtures
      with cephalosporins were clear when viewed in normal fluorescent room light and
      with a Tyndall beam. Measured turbidity and particulate content were low and
      exhibited little change. The cefazolin sodium-containing samples were colorless
      throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had
      a slight yellow tinge initially, and the room temperature samples became a frank
      yellow color after 5 days. The refrigerated samples did not change color. High
      performance liquid chromatography analysis found little or no loss of linezolid
      in any sample stored at either temperature throughout the study. Cefazolin sodium
      and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7
      days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime
      for only 24 hours before cephalosporin decomposition exceeded 10%. Ceftriaxone
      sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4
      degrees C and more than 20% loss occurred in 24 hours at 23 degrees C.
      CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram
      and ceftazidime 2 grams were physically compatible and chemically stable for at
      least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day,
      respectively, at 23 degrees C protected from light. Admixtures of linezolid with
      ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23
      degrees C, which precludes admixture of the two drugs.

PMID- 10932461
TI  - Compatibility screening of linezolid injection during simulated Y-site
      administration with other drugs and infusion solutions.
AB  - OBJECTIVE: To evaluate the physical compatibility of linezolid injection (Zyvox
      Pharmacia) during simulated Y-site administration with 8 infusion solutions and
      110 selected other drugs. DESIGN: Controlled experimental trial. SETTING:
      Laboratory. INTERVENTIONS: Five-milliliter samples of linezolid injection 2 mg/mL
      were mixed with 5 mL samples of the selected infusion solutions and the selected
      other drugs diluted in 5% dextrose injection, or, if necessary to avoid
      incompatibility with the diluent, 0.9% sodium chloride injection. MAIN OUTCOME
      MEASURES: Visual examinations of the samples were performed in normal fluorescent
      light with the unaided eye and using a Tyndall beam (high-intensity
      monodirectional light source) to enhance visualization of small particles and low
      level haze. The turbidity of each sample was measured, and for samples that did
      not exhibit visible precipitation, the particle content was measured, as well.
      All of the samples were assessed initially and at 1 and 4 hours. RESULTS: All of
      the infusion solutions and most of the test drugs were physically compatible with
      linezolid injection during the 4-hour observation period. Physical
      incompatibilities resulted when linezolid injection was combined with five of the
      drugs: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine
      isethionate, and phenytoin sodium. Precipitation, turbidity formation, and/or
      unacceptable changes in measured haze levels were observed. CONCLUSION: Linezolid
      2 mg/mL was physically compatible for 4 hours at room temperature with all 8
      infusion solutions tested and 105 of the drugs tested. Simultaneous Y-site
      administration of linezolid injection with the five drugs resulting in physical
      incompatibilities should be avoided.

PMID- 10932462
TI  - Compatibility and stability of linezolid injection admixed with aztreonam or
      piperacillin sodium.
AB  - OBJECTIVE: To evaluate the physical compatibility and chemical stability of
      linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with aztreonam (Azactam-Squibb)
      2 grams and separately with piperacillin sodium (Pipracil-Lederle) 3 grams over 7
      days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial.
      SETTING: Laboratory. INTERVENTIONS: Test samples were prepared by adding the
      required amount of aztreonam or piperacillin sodium to separate bags of linezolid
      injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical compatibility and
      chemical stability based on drug concentrations initially and after 1, 3, 5, and
      7 days of storage at 4 degrees C and 23 degrees C. RESULTS: All of the linezolid
      admixtures with aztreonam and with piperacillin sodium were clear when viewed in
      normal fluorescent room light and with a Tyndall beam. Measured turbidity and
      particulate content were low and exhibited little change throughout the study at
      both storage temperatures. High-performance liquid chromatography analysis found
      little or no loss of linezolid in any sample stored at either temperature
      throughout the study. Aztreonam in the linezolid admixtures was stable for 7
      days, exhibiting less than 5% loss at 4 degrees C and 9% loss at 23 degrees C.
      Piperacillin sodium in the linezolid admixtures was stable for 7 days at 4
      degrees C, exhibiting no loss, but was stable for only 3 days at 23 degrees C
      with losses of about 5%. Losses had increased to 9% to 12% after 5 days of
      storage at room temperature. CONCLUSION: Admixtures of linezolid 200 mg/100 mL
      with aztreonam 2 grams or piperacillin sodium 3 grams were physically compatible
      and chemically stable for at least 7 days stored at 4 degrees C and for 7 days or
      3 days, respectively, at 23 degrees C.

PMID- 10932463
TI  - Major depression in women: a review of the literature.
AB  - OBJECTIVE: To promote pharmacists' understanding and recognition of major
      depression in women and to review gender/sex-specific differences in its
      prevalence, etiology, risk factors, clinical features, course, and management.
      DATA SOURCES: Clinical literature on this topic in the English language since
      1990, searched through MEDLINE. STUDY SELECTION: Selected review articles and
      clinical trials from peer-reviewed journals. DATA SYNTHESIS: Epidemiologic data
      from diverse cultures indicate that the lifetime prevalence of major depression
      is twice as high in women as in men. The artifact, biological, and psychosocial
      hypotheses have each been proposed to explain the predominance of lifetime
      depression in women. Major depression is a multifactorial disorder and is
      influenced by numerous risk factors, including age, socioeconomic status,
      childhood history of sexual abuse, and recent stressful life events. Clinical
      course and presentation tend to differ between women and men. Women may
      experience different types of depression during various reproductive or life
      stages, including premenses, pregnancy, postpartum, and menopause. Treatment for
      major depression includes psychosocial therapy, pharmacotherapy, and
      electroconvulsive therapy. The literature indicates that major depression is
      often underrecognized and undertreated. CONCLUSION: Biological and psychosocial
      factors contribute to the higher vulnerability of women to major depression. The
      biological-psychosocial origins of depression in women may require a
      multidimensional approach to treatment. By providing education about this
      disease, referring individuals with signs and symptoms of depression for
      evaluation, and encouraging appropriate use of antidepressants, pharmacists can
      improve the detection and treatment of major depression.

PMID- 10932464
TI  - Drug utilization review: mechanisms to improve its effectiveness and broaden its
      scope. The U.S. Pharmacopeia Drug Utilization Review Advisory Panel.
AB  - OBJECTIVE: To address important problems and needed changes in online and
      retrospective drug utilization review (DUR) programs. Emphasis is placed on
      reliability of DUR criteria and the shift of traditional retrospective DUR
      programs toward disease management and health care outcomes. DATA SOURCES:
      Published literature evaluating the role of online and retrospective DUR
      programs. STUDY SELECTION: Particular attention was given to studies assessing
      DUR criteria reliability and new interventions with retrospective DUR programs.
      DATA SYNTHESIS: A literature review was conducted along with an expert summary
      from the U.S. Pharmacopeia Drug Utilization Review Advisory Panel. Studies have
      revealed variations in DUR criteria that could be affecting clinical practice and
      patient care. Appropriate formal methodologies and use of consistent procedures
      in developing online prospective DUR programs and systems could help resolve
      these problems. Traditional retrospective DUR is also shifting to incorporate
      disease management and methodologies from health outcomes and pharmacoeconomics
      studies. CONCLUSIONS: Refinements are needed to improve the reliability and
      validity of online DUR criteria and to minimize false positive messages.
      Databases created as a result of DUR efforts have been used in new and innovative
      ways to incorporate health outcomes data and disease management interventions.
      Additional outcomes data, combined with quality assurance efforts, should
      increase the utility of DUR/disease management efforts in evaluating health
      systems while improving the effectiveness and efficiency of pharmacists' health
      care interventions.

PMID- 10932465
TI  - Using the Internet for research.
AB  - OBJECTIVE: (1) To give an overview of research tools, techniques, and resources
      that are available on the Internet; and (2) to identify valid, pharmacy-related
      information that will reduce uncertainty in the problem-solving activities of
      practitioners. DATA SOURCES: The World Wide Web. STUDY SELECTION: Examples cited
      in the article were evaluated according to the criteria offered in the text as a
      prerequisite for their inclusion. DATA SYNTHESIS: Functional aspects of the
      Internet include communication, commerce, and content. Because a lack of control
      has led to mixed information quality, the use of Internet-based information for
      patient care and professional decision making should be subject to rigorous
      screening criteria. Pharmacists can use Web browsers combined with excellent
      search engines and search techniques to identify quality resources, including
      primary, secondary, and tertiary literature, either fee-based or free, and that
      can be sought actively or distributed on a schedule directly to the desktop of
      the pharmacist. CONCLUSION: The Internet can be an immensely helpful research
      tool, if used appropriately. Whether actively searching or passively receiving
      useful updates, the Internet can function as a value-added asset to any pharmacy
      practice.

PMID- 10932466
TI  - Practice models used by pharmacists in rural Minnesota to obtain Medicare
      reimbursement.
AB  - OBJECTIVES: (1) Define "incident-to" rules for Medicare reimbursement; (2)
      Describe how pharmacists can meet incident-to rules; (3) Provide examples of
      models of practice in rural areas that could be useful for meeting incident-to
      rules; and (4) Develop a strategy for creating a pharmacy practice model that
      could meet Medicare reimbursement rules in rural areas. DESIGN AND PARTICIPANTS:
      A survey of participants from the Pharmacy Rural Education, Practice and Policy
      Institute and the College of Pharmacy, University of Minnesota. SETTING:
      Community, hospital, and clinic practice sites in rural Minnesota. RESULTS: Four
      distinct models of practice have evolved that meet the incident-to rules of
      Medicare for reimbursement. Travel, proximity to physicians, and employment are
      the major determinants of the models described. CONCLUSION: Pharmacists in rural
      areas have demonstrated the ability to satisfy the incident-to rules for Medicare
      reimbursement. Collaborative agreements with physicians must include specific
      employment, practice, and supervisory relationships in order to satisfy these
      rules.

PMID- 10932467
TI  - Peptic ulcer disease: let's help cure it.

PMID- 10932469
TI  - Angiogenesis: a "common denominator" of disease?

PMID- 10932468
TI  - Smoking and the need for vaccination.

PMID- 10932470
TI  - New players, new services: e-scripts revisited.

PMID- 10932471
TI  - Time estimation by patients with frontal lesions and by Korsakoff amnesics.
AB  - We studied time estimation in patients with frontal damage (F) and alcoholic
      Korsakoff (K) patients in order to differentiate between the contributions of
      working memory and episodic memory to temporal cognition. In Experiment 1, F and
      K patients estimated time intervals between 10 and 120 s less accurately than
      matched normal and alcoholic control subjects. F patients were less accurate than
      K patients at short (< 1 min) time intervals whereas K patients increasingly
      underestimated durations as intervals grew longer. F patients overestimated short
      intervals in inverse proportion to their performance on the Wisconsin Card
      Sorting Test. As intervals grew longer, overestimation yielded to underestimation
      for F patients. Experiment 2 involved time estimation while counting at a
      subjective 1/s rate. F patients' subjective tempo, though relatively rapid, did
      not fully explain their overestimation of short intervals. In Experiment 3,
      participants produced predetermined time intervals by depressing a mouse key. K
      patients underproduced longer intervals. F patients produced comparably to normal
      participants, but were extremely variable. Findings suggest that both working
      memory and episodic memory play an individual role in temporal cognition.
      Turnover within a short-term working memory buffer provides a metric for temporal
      decisions. The depleted working memory that typically attends frontal dysfunction
      may result in quicker turnover, and this may inflate subjective duration. On the
      other hand, temporal estimation beyond 30 s requires episodic remembering, and
      this puts K patients at a disadvantage.

PMID- 10932472
TI  - Components of verbal learning and hippocampal damage assessed by T2 relaxometry.
AB  - We studied a group of 31 temporal lobe epilepsy patients (25 left, 6 right) with
      unilateral hippocampal sclerosis evident on magnetic resonance imaging. Single
      slice T2 relaxation times were acquired for the left and right hippocampi.
      Principal components analysis of preoperative memory data resulted in two factors
      that reflect a distinction between arbitrary and semantic forms of verbal recall.
      The former component correlated with left hippocampal T2 relaxation time, while
      the latter component did not. This study suggests that variation in left
      hippocampal integrity is more related to the acquisition of arbitrary associates
      than semantically structured material, and reinforces the possibility that the
      left temporal lobe is functionally heterogeneous with respect to memory.

PMID- 10932473
TI  - Toward solving the inferential problem in laterality research: effects of
      increased reliability on the validity of the dichotic listening right-ear
      advantage.
AB  - As noted by Satz, the prevalence of lateralized language in the general
      population is underestimated substantially by the proportion of people who show
      the typical asymmetry on a laterality task. In a series of two dichotic listening
      experiments with a total of 171 right-handers and 170 left-handers, we tested the
      hypothesis that increased reliability of measurement will lead to increased
      classification accuracy. Experiment 1 showed that neither the frequency nor
      magnitude of the right-ear advantage (REA) for fused rhyming words increased as
      the number of trials increased from 120 to 480. Ear-difference scores were highly
      reliable (r = .85), even when based on 120 trials. Experiment 2, which involved
      lists of dichotic word pairs, yielded similar results. Even though retest
      reliability of the ear-difference score for 132 word pairs was only .45, neither
      the incidence nor strength of the REA increased significantly when the number of
      pairs was increased to 528. The results indicate that the poor classification
      accuracy of dichotic listening tasks cannot be attributed to unreliability.

PMID- 10932474
TI  - Verbal working memory in HIV-seropositive drug users.
AB  - Recent evidence suggests that HIV-seropositive drug users are impaired on tasks
      of visuospatial working memory compared with drug users seronegative for HIV. In
      the current study we evaluated the performance of 30 HIV-seropositive male drug
      users and 30 risk-matched seronegative controls on two measures of verbal working
      memory, the Listening Span and the verbal Self Ordered Pointing Task. Impaired
      working memory performance was significantly more common among HIV-seropositive
      persons compared to controls, with the highest incidence of deficit among
      symptomatic participants. These findings indicate that working memory deficits in
      persons with HIV are not domain-specific and can be demonstrated reliably in drug
      users.

PMID- 10932475
TI  - Evaluation of reading comprehension with neuropsychological and event-related
      brain potential (ERP) methods.
AB  - Evidence is presented for the efficacy of a new method of assessing reading
      comprehension using a standardized reading test that was formatted for computer
      presentation with simultaneous event-related brain potential (ERP) recordings.
      Reading comprehension abilities of 23 healthy undergraduate students were
      evaluated using ERPs. The results revealed a differential ERP response pattern
      for correct and incorrect test items. These response patterns were observed at
      individual participant levels. The findings provided further support for the use
      of ERPs in the neuropsychological assessment of patients who are difficult or
      impossible to assess using behavioral responses because of concomitant motoric
      and/or communicative limitations.

PMID- 10932476
TI  - Factors influencing outcome following mild traumatic brain injury in adults.
AB  - This study aimed to investigate outcome in adults with mild traumatic brain
      injury (TBI) at 1 week and 3 months postinjury and to identify factors associated
      with persisting problems. A total of 84 adults with mild TBI were compared with
      53 adults with other minor injuries as controls in terms of postconcussional
      symptomatology, behavior, and cognitive performance at 1 week and 3 months
      postinjury. At 1 week postinjury, adults with mild TBI were reporting symptoms,
      particularly headaches, dizziness, fatigue, visual disturbance, and memory
      difficulties. They exhibited slowing of information processing on
      neuropsychological measures, namely the WAIS-R Digit Symbol subtest and the Speed
      of Comprehension Test. By 3 months postinjury, the symptoms reported at 1 week
      had largely resolved, and no impairments were evident on neuropsychological
      measures. However, there was a subgroup of 24% of participants who were still
      suffering many symptoms, who were highly distressed, and whose lives were still
      significantly disrupted. These individuals did not have longer posttraumatic
      amnesia (PTA) duration. They were more likely to have a history of previous head
      injury, neurological or psychiatric problems, to be students, females, and to
      have been injured in a motor vehicle accident. The majority were showing
      significant levels of psychopathology. A range of factors, other than those
      directly reflecting the severity of injury, appear to be associated with outcome
      following mild TBI.

PMID- 10932477
TI  - Numbers, models, and understanding of natural intelligence: computational
      neuroscience in the service of clinical neuropsychology.

PMID- 10932478
TI  - How hallucinations may arise from brain mechanisms of learning, attention, and
      volition.
AB  - This article suggests how brain mechanisms of learning, attention, and volition
      may give rise to hallucinations during schizophrenia and other mental disorders.
      The article suggests that normal learning and memory are stabilized through the
      use of learned top-down expectations. These expectations learn prototypes that
      are capable of focusing attention upon the combinations of features that comprise
      conscious perceptual experiences. When top-down expectations are active in a
      priming situation, they can modulate or sensitize their target cells to respond
      more effectively to matched bottom-up information. They cannot, however, fully
      activate these target cells. These matching properties are shown to be essential
      towards stabilizing the memory of learned representations. The modulatory
      property of top-down expectations is achieved through a balance between top-down
      excitation and inhibition. The learned prototype is the excitatory on-center in
      this top-down network. Phasic volitional signals can shift the balance between
      excitation and inhibition to favor net excitatory activation. Such a volitionally
      mediated shift enables top-down expectations, in the absence of supportive bottom
      up inputs, to cause conscious experiences of imagery and inner speech and thereby
      to enable fantasy and planning activities to occur. If these volitional signals
      become tonically hyperactive during a mental disorder, the top-down expectations
      can give rise to conscious experiences in the absence of bottom-up inputs and
      volition. These events are compared with data about hallucinations. The article
      predicts where these top-down expectations and volitional signals may act in the
      laminar circuits of visual cortex and, by extension, in other sensory and
      cognitive neocortical areas, and how the level of abstractness of learned
      prototypes may covary with the abstractness of hallucinatory content. A similar
      breakdown of volition may lead to delusions of control in the motor system.

PMID- 10932479
TI  - Continuum model of mnemonic and amnesic phenomena.
AB  - Amnesia in its various forms is characterized by defects in one or more
      components of a complex system. Implantation of short-term memory occurs in the
      hippocampus, while long-term memory is essentially located in the neocortex;
      these regions are interconnected through complex synaptic structures. In the
      hippocampus, physiological data show that, as predicted by Hebb, excitatory
      synapses between nearby excitatory cells become strengthened by simultaneous
      activation. In contrast with this local process, the preponderance of clinical
      and experimental evidence indicates that cortical recall of a "memory" is the
      reconstruction of fragments stored in different synaptically distant brain
      regions. A mathematical model of memory must reconcile this apparent
      contradiction as well as explain how many different memories and "ideas" can be
      assembled within a given anatomical area. Continuum theory, which treats an
      ensemble of "cell assemblies" or neural networks, offers a step in this
      direction. Linear analysis using this approach shows that it is the nature of the
      neural continuum to generate activity waves of wavelength greater than synaptic
      connection ranges. These waves grow under certain circumstances, and their
      wavelength is controlled by the synaptic parameters. Both hippocampal and
      cortical tissue are subject to such wave growth. In the hippocampus, the local
      Hebbian strengthening controls the global wave growth, making the difference
      between wave decay and growth. The cortical wave structure can become very
      complex, so that reproducible memory recall as well as "creative thought" can be
      accommodated in the theory. Deficits in the functioning of the system may also be
      evaluated potentially by means of "goodness-of-fit" of the clinical and spatially
      resolved data with the model.

PMID- 10932480
TI  - Simulation of cognitive disturbances by a dynamic threshold semantic neural
      network.
AB  - A neural network model with dynamic thresholds, asymmetric connections, and
      clustered memories simulates spread activation that is hypothesized for semantic
      networks in the brain. By altering the parameters of the dynamic threshold a
      large range of disturbances can be generated in the model. These disturbances
      show metaphorical resemblance to certain general clinical descriptions of mental
      disturbances found in psychiatric patients engaged in various cognitive tasks.
      Even though the model is highly theoretical and metaphoric, it may help to gain
      certain insights into the relation between alterations of certain neural
      parameters, for example, thresholds and connectivity, and clinical symptoms in
      patients.

PMID- 10932481
TI  - Errors in a nonlinear graphic-semantic mapping task resulting from lesions in
      Boltzmann machine: is it relevant to dyslexia?
AB  - One of the most fascinating aspects of brain research is the subject of language.
      As in many other cases, the malfunctions that occur in different persons for
      various reasons give us insight on the mechanisms that support our ability to
      talk, read and listen. Following the work of Plaut and associates, we deal with
      the dyslexia disorder, which is the overall name for a large number of reading
      disorders. A Boltzmann machine neural network scheme was trained to implement the
      nonlinear mapping task of graphic representation into semantic representation,
      which may model the brain sections responsible for the translation of a written
      word into meanings and syllables. After training, various types of lesions were
      applied and the performance of the network was tested in order to measure the
      effect of each lesion on the error rate and type distribution that were detected.
      The system's errors were classified into several categories and the distribution
      of errors between the categories was studied. Using the simulations, it is
      demonstrated that a finite scheduling process in the Boltzmann machine causes the
      distribution of the network's errors to be unique and different from its expected
      error distribution. The phenomenon is given a mathematical explanation rooted in
      the statistical mechanics basics of the Boltzmann machine. Test results suggest
      the localization of certain reading functions within the network. Comparison is
      made to relevant types of dyslexia and shows resemblance in major symptoms as
      well as in certain known side effects.

PMID- 10932482
TI  - Virtual lesions and the not-so-modular brain.
AB  - Because lesions usually affect contiguous areas of the brain, cognitive
      neuropsychology has generally posited modularity of brain function, assuming that
      specific regions of the brain have specific dedicated functions. However, a
      review of 36 published functional neuroimaging studies suggests that functions
      are distributed over multiple regions. Or, in other words, specific brain regions
      are usually multifunctional. By a technique of "virtual lesions," I measure the
      contribution that regions of the brain make to tasks imaged in 36 PET
      experiments, and propose a new and more detailed interlink between
      neuropsychology and functional neuroimaging.

PMID- 10932484
TI  - Bronchial artery embolization for hemoptysis.
AB  - BACKGROUND: Massive hemoptysis is a life-threatening condition. Since treatment
      from surgery has high mortality, bronchial artery embolization (BAE) is now safer
      and may be good for chronic hemoptysis as well. MATERIAL AND METHOD: Ten patients
      (6 male, 4 female) with hemoptysis underwent BAE. Five patients had massive life
      threatening hemoptysis (4 tuberculosis and 1 bronchogenic carcinoma) and 5 had
      chronic hemoptysis (4 tuberculosis and 1 bronchogenic carcinoma). All patients
      received BAE by transfemoral arterial approach using gelfoam particles and Ivalon
      as the embolized materials. Bronchial arteries were abnormal in all cases except
      one patient who had bronchogenic carcinoma supplied by the acromiothoracic artery
      to the left upper lobe. RESULTS AND CONCLUSION: Chest radiograph may correlate
      well with angiographic findings if there is one lobar lesion, but multiple lobar
      lesions showed no correlation between the two modalities. Hypervascularity was a
      universal findings in all patients. Other angiographic findings were enlarged
      bronchial or nonbronchial arteries, systemic to pulmonary anastomosis,
      pseudoaneurysm, and extravasation of contrast media. The immediate result of BAE
      achieved 100 per cent but follow-up showed only a 70 per cent success rate with
      one mortality from recurrent massive hemoptysis and two recurrent cases due to
      complications. Ivalon which is a permanent embolized material may be useful for
      recurrent hemoptysis.

PMID- 10932483
TI  - Guideline for the pharmacotherapy of treatment-resistant schizophrenia. Royal
      College of Psychiatrists of Thailand.
AB  - The authors proposed to develop an evidence-based guideline relevant to drug use
      for treatment-resistant schizophrenia (TRS), which will be called "Guideline for
      the Pharmacotherapy of Treatment-Resistant Schizophrenia or PTRS Guideline". The
      authors performed a MEDLINE search (between 1966 and December 1998) and
      classified the study designs of those trials by using the system proposed by the
      Agency for Health Care Policy and Research (AHCPR). The levels of evidence were
      graded and recommendations were made by the use of a system modified from that of
      the AHCPR. One hundred and sixty-three articles met the inclusion criteria for
      the review. For a schizophrenic patient who does not respond to a classical
      antipsychotic, physicians should switch from the first classical antipsychotic to
      the second one, which belongs to a different class. A schizophrenic patient who
      does not respond to at least two adequate trials of classical antipsychotics
      should be classified as a TRS patient. Clozapine should be considered as a first
      line treatment for TRS. Risperidone should be considered in a TRS patient who
      refuses to have regular blood monitoring or has contraindication for clozapine.
      Physicians should use this guideline to accompany others that suggest the
      overview of treatment for schizophrenia. Appropriate application and the
      limitations of the guideline are also discussed.

PMID- 10932485
TI  - The Thai version of Aachen aphasia test (THAI-AAT).
AB  - The lack of a standardized Thai Language aphasia test raises difficulties not
      only with the assessment and treatment planning for the clinical but also with
      the accurate diagnosis and the reliable incidence for research on aphasiology in
      Thailand. This study aimed to use the Thai version of German Aachen aphasia (THAI
      AAT), which is systematically adapted according to well-defined linguistic
      criteria and psychometric requirement, to assess the language deficit of Thai
      aphasic patients. The subjects participating in this study were 125 aphasia
      patients, 60 non-aphasic brain damaged patients and 120 normal subjects. The
      result revealed that the THAI-AAT is linguistically parallel in test design and
      fulfills the same psychometric properties as the original. The THAI-AAT obtains
      the goals: to differential diagnosis of aphasia distinguishing it from non
      aphasic disturbance and to identify the type of aphasic syndrome.

PMID- 10932486
TI  - Effect of omeprazole on gastric mucosa and serum levels of amoxicillin in
      patients with non-ulcer dyspepsia.
AB  - The aim of this study was to determine the interaction between omeprazole and
      amoxicillin, being common agents used in the eradication regimen for H. pylori
      infection. Amoxicillin concentrations in gastric mucosa and serum were
      quantitatively analysed in 12 patients with non-ulcer dyspepsia following the
      administration of one week duration of placebo as group I and omeprazole as group
      II. The study was a blind, cross-over design with a one week wash out period
      between the two treatment groups. Six antral gastric mucosa were biopsied 90
      minutes after oral administration of amoxicillin. Blood samples were collected
      before and after administration at intervals up to 6 hours. All samples were
      analysed for amoxicillin concentration using the HPLC technique. Highly
      intersubject variations of amoxicillin concentrations were observed. The
      concentration of amoxicillin in gastric mucosa ranged from 0.00-1.74 and 0.00
      1.25 micrograms/mg for group I and group II, respectively, with the mean
      concentration of 0.25 +/- 0.48 microgram/mg for group I and 0.28 +/- 0.40
      microgram/mg for group II. The difference was not statistically significant (p =
      0.89). Pharmacokinetic parameters of amoxicillin in serum following regimen I and
      regimen II were not significantly different (p > 0.05). The mean Cmax values were
      14.62 +/- 5.39 and 12.65 +/- 4.76 micrograms/ml, the Tmax were 2.3 +/- 1.0 and
      2.0 +/- 0.9 hour and the AUC0-6 were 40.79 +/- 13.26 and 38.75 +/- 15.04
      micrograms/ml.h in the group I and group II, respectively. From these results, we
      concluded that omeprazole has no effect on gastric mucosa level nor serum levels
      of amoxicillin. The therapeutic efficacy of using these two agents in the
      eradication regimen of H. pylori may be related to other factors rather than
      pharmacokinetic interaction.

PMID- 10932488
TI  - Correlation of oocyte morphology with fertilization rate and embryo quality after
      intracytoplasmic sperm injection.
AB  - To determine whether the morphology of the oocyte assessed under light microscopy
      is related to the results of intracytoplasmic sperm injection (ICSI). 135 ICSI
      oocytes from 15 patients were analyzed. Transvaginal ultrasound-guided oocytes
      retrieval with oocyte morphology evaluation based on shape of the first polar
      body and perivitelline space followed by ICSI. After 48 hours, embryo quality was
      evaluated and compared to each pre-injected oocyte morphology. Normal
      fertilization was achieved in 81.5 per cent of the oocytes (110/135). Abnormal
      fertilization (3 pronuclei) was 1.5 per cent (2/135). Fertilization rate of
      oocytes with good morphology was higher than those with poor morphology, but
      there was no statistical significance (82.4% vs 79.5%; p > 0.05). Oocytes with
      good morphology were significantly fertilized to be embryos with good quality (p
      < 0.001). This study suggests that oocyte morphology correlates with embryo
      quality after ICSI.

PMID- 10932487
TI  - The usefulness of serum insulin-like growth factor-1 (IGF-1) and insulin-like
      growth factor binding protein-3 (IGFBP-3) for evaluation of children with short
      stature.
AB  - The diagnostic value of serum insulin-like growth factor-1 (IGF-1) and insulin
      like growth factor binding protein-3 (IGFBP-3) was studied in 24 growth hormone
      deficient (GHD) and 36 normal variant short stature (NVSS) children. The serum
      IGF-1 and IGFBP-3 concentrations were markedly below the 5th centile for
      chronological age in all 24 GHD children, but were in the low normal range for
      age in most of the NVSS children. The concentrations of IGF-1 and IGFBP-3
      significantly correlated with peak GH concentration, height age, and bone age. To
      account for the age- and sex-dependency, IGF-1 and IGFBP-3 levels were
      transformed to standard deviation score (SDS). Using the -2 SDS as a cut-off
      level to differentiate between GHD and NVSS, the diagnostic value of IGF, as well
      as IGFBP-3, showed sensitivity 100 per cent, specificity 66.7 per cent, and
      accuracy 80 per cent. The combined use of IGF-1 and IGFBP-3 < -2 SDS improved the
      diagnostic value with sensitivity 100 per cent, specificity 77.8 per cent, and
      accuracy 86.7 per cent. We concluded that the serum concentrations of IGF-1 and
      IGFBP-3 could reflect endogenous GH secretion and could be used as a screening
      evaluation of GH status in short children.

PMID- 10932489
TI  - DTH responsiveness of HIV-infected Thai adults.
AB  - A study was carried out in Thailand to determine the frequency of reactivity to
      delayed-type hypersensitivity (DTH) skin tests used for the staging of HIV
      patients in the United States. A four-antigen panel which included tetanus toxoid
      (1:10), Candida (1:10), mumps and Trichophyton antigens was assessed in 221 adult
      subjects from across the full immunological spectrum of HIV disease. Complete
      anergy was found in 38 per cent of 73 subjects with CD4 counts of 0-200 cells/ml
      and in 6 per cent of 78 subjects with 201-400 cells/ml. Partial anergy (response
      to 1 of 4 antigens) was found in 26 per cent of the 0-200 cell/ml group and
      decreased progressively with increasing CD4 cell count. Results suggested that a
      3-member recall antigen panel would provide nearly all the clinically useful
      information gained by the more standard 4-member panel. In conclusion, DTH skin
      testing was confirmed to provide a method of assessing the integrity of cellular
      immune function of HIV-infected Thai adults which correlated with disease
      progression.

PMID- 10932490
TI  - Outcome of preterm premature rupture of membranes.
AB  - OBJECTIVE: To study the incidence and outcome of preterm premature rupture of
      membranes (PPROM). DESIGN: Cross-sectional study. SETTING: Department of
      Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University.
      SUBJECTS: Ninety five PPROM women who were expectant management and delivered
      between January 1, 1997 and December 31, 1997. RESULTS: The incidence of PPROM
      was 7.2 per 1000 deliveries. There were 51 women in the gestational age group at
      or below 34 weeks and 44 women in the gestational age group above 34 weeks.
      Gestational age, total antenatal care visits, total weight gain and neonatal
      birth weight were significantly lower in the gestational age group at or below 34
      weeks (p < 0.05). Abnormal delivery, maternal and neonatal complications were
      significantly more common in the gestational age group at or below 34 weeks (p <
      0.05). Total maternal and neonatal hospital-stay comprised significantly more
      days in the gestational age group at or below 34 weeks (p < 0.05). CONCLUSION:
      Maternal and neonatal outcome were more unfavorable in the gestational age group
      at or below 34 weeks of PPROM. Expectant management should intervene at the
      gestational age at or below 34 weeks of PPROM due to unfavorable maternal and
      neonatal outcome.

PMID- 10932491
TI  - The Thai version of the Positive and Negative Syndrome Scale (PANSS) for
      schizophrenia: criterion validity and interrater reliability.
AB  - The Positive and Negative Syndrome Scale or PANSS is a standardized instrument
      for the measurement of positive and negative symptoms of schizophrenia. The PANSS
      was widely accepted by researchers and was translated into many languages. It is
      now translated into Thai, the PANSS-T. The PANSS-T was carefully assessed for its
      reliability and criterion validity in relation to the PANSS in Thai schizophrenic
      patients. The results were satisfactory. The PANSS-T can now be used by Thai
      researchers in clinical studies of schizophrenia that involve the measurement of
      positive and negative symptoms.

PMID- 10932492
TI  - Survival of children with AIDS: experience in a university hospital in northeast
      Thailand.
AB  - The survival experience of pediatric AIDS patients from three points: birth, age
      at first symptom and age at AIDS diagnosis (by the WHO definition) was studied.
      We had 90 subjects, 46 males and 44 females. They were under 15 years of age and
      were diagnosed as having perinatally-acquired pediatric AIDS. The children came
      to Srinagarind Hospital between January, 1989 and December, 1997. They were
      followed-up until April 30, 1998. Patients who did not come to the hospital were
      traced by confidential mail. The two most common first symptoms were chronic
      diarrhea (36.7%) and persistent lower respiratory tract infection (34.4%). The
      median age at the first symptom was four months (95% CI = 3 to 5 months) and the
      median age at diagnosis was 13 months (95% CI = 11 to 15 months). Thirty-nine
      cases received antiretroviral treatment, either AZT, ddI or both. Forty-five
      cases died, 18 cases lived to the end of the study, 27 could not be followed-up.
      A survival curve was calculated according to the Kaplan and Meier method using
      SPSS version 6.0. The 1- and 2-year survival rates from the time of the first
      symptom were 75.3 per cent (95% CI = 65.8% to 84.7%) and 60.3 per cent (95% CI =
      49.0% to 71.6%). The corresponding survival rates from AIDS diagnosis were 59.7
      per cent (95% CI = 48.4% to 71.1%) and 42.8% (95% CI = 30.3% to 55.3%),
      respectively.

PMID- 10932493
TI  - Maintenance ECT in treatment-resistant schizophrenia.
AB  - Although electroconvulsive therapy (ECT) has been used to treat schizophrenia
      since its inception in 1938, its efficacy as long-term treatment is still
      controversial. A 2-Phase, prospective study has been conducted in 21 patients
      with schizophrenia. The duration of study was 1 year. Bilateral ECT combined with
      flupenthixol (18-24 mg/day) was used throughout. Brief Psychiatric Rating Scale
      (BPRS), Global Assessment of Functioning (GAF), and Mini-Mental-State Exam (MMSE)
      were used to measure the outcome. No patients suffered relapses. There were
      marked reductions in BPRS scores (73 per cent and 70 per cent), and increases in
      GAF scores (68 per cent and 91 per cent), at the end of Phases I and II,
      respectively. This study suggests a long-term efficacy of ECT combined with
      neuroleptic therapy in patients with schizophrenia.

PMID- 10932494
TI  - The clavicular fracture: a biomechanical study of the mechanism of clavicular
      fracture and modes of the fracture.
AB  - A clavicle is an S-shaped long bone whose biomechanical behavior is unlike that
      of a straight tubular long bone. When a clavicle is under a compression load
      along the axis, the force produces a middle one-third clavicular fracture. The
      present study is a biomechanical study to confirm the clinical observations of
      the mechanism of the fracture and to discover the tension site and compression
      site of the fracture, using 12 fresh cadaveric clavicles, a universal testing
      machine and two special grips. One grip was constructed with a contour like a
      sternoclavicular articulation. The grip was mounted at the medial end of the
      clavicle. Another grip was constructed with a contour like an acromioclavicular
      articulation. The grip was mounted at the lateral end of the clavicle. A load was
      applied to the lateral clavicle like a force transmitting from the weight of the
      shoulder girdle. A load was also applied to the medial clavicle like a force from
      the sternocleidomastoid muscle. A compression load was applied along the axis of
      the testing clavicle through the upper grips by using a universal testing
      machine. The result found that the average load of the clavicular fracture was
      1526.19 N. The fracture occurred at the middle one-third of the clavicle in the
      region of the curve of the lateral clavicle changing to the curve of the medial
      clavicle. While primatic cross section of the clavicle at the fracture site
      determined a tension and a compression site of the fracture, the fracture took
      the superoanterior aspect of the clavicle as a tension site and posteroinferior
      aspect as a compression site. The fracture had a ratio of length of the lateral
      fragment to the total length of the clavicle of 0.49. This study confirmed that a
      compression load along the axis of the clavicle produces a middle one-third
      clavicular fracture as in clinical observation and the fracture took the
      superoanterior aspect of the clavicle as a tension site.

PMID- 10932495
TI  - Phase II trial of tropisetron and dexamethasone in the prevention of cisplatin
      induced emesis.
AB  - Thirty-one patients treated with 58 cycles of cisplatin-based chemotherapy at a
      dose > 80 mg/m2 were enrolled into the study using tropisetron and dexamethasone
      in the prevention, of cisplatin-induced emesis. There was 87.9 per cent complete
      control, 10.3 per cent major control, and 1.7 per cent failure for nausea episode
      on the first day of cycle. For the vomiting control, there was 96.6 per cent
      complete control, 3.4 per cent major control, and no failure. After the second
      day, the percentage of complete control increased gradually for both nausea and
      vomiting. The complete control for acute nausea and vomiting was 85.7 per cent
      and 92.9 per cent, respectively. The efficacy for delayed emesis was lower. There
      was 76.4 per cent complete control for delayed nausea and 85.7 per cent for
      delayed vomiting. The treatment was well tolerated without any serious adverse
      events related to tropisetron. Only hiccups was reported in 4 patients and
      recovered spontaneously at the end of the cycle. Combination of tropisetron and
      dexamethasone is an effective and safe antiemetic regimen in the prevention of
      cisplatin-induced emesis.

PMID- 10932496
TI  - Efficacy of UFT plus oral leucovorin in advanced colorectal cancer: a multicenter
      study.
AB  - PURPOSE: To evaluate the efficacy and toxicity of UFT plus oral leucovorin in
      advanced colorectal cancer. MATERIAL AND METHOD: Twenty cases of advanced
      colorectal cancer were entered into the study. All patients must have histologic
      proof and have measurable disease. Prior to the treatment all patients should
      have normal baseline hematology and normal liver and renal function, ECOG
      Performance status < or = 2 and age 18-75 years. Chemotherapeutic drugs consisted
      of UFT 350 mg/m2/day divided into 3 doses (8 hours apart) plus oral leucovorin 15
      mg every 8 hours. Duration of treatment was 21 days per each cycle. Treatment was
      recycled every 28 days. RESULTS: Four cases (22.2%) had partial responses and six
      cases (33.3%) had stable disease. Duration of response was 4(+)-7+ months.
      Toxicity was darkened skin, mild diarrhea and mild alopecia. CONCLUSION: UFT plus
      oral leucovorin was one of the active regimens in the treatment of advanced
      colorectal cancer.

PMID- 10932497
TI  - Toxoplasma gondii antibody in HIV-infected persons.
AB  - Toxoplasmosis in an immunocompromised host was not documented in Thailand until
      1992 when HIV/AIDS infection became pandemic. Patients with toxoplasmic
      encephalitis and cerebral abscess were recorded, particularly from the northern
      part of the country. However, data on the prevalence of the disease in HIV/AIDS
      patients is not yet available. In this study the authors determine the prevalence
      of T. gondii antibody in HIV persons. During a two-year period 312 serum samples
      of which 190 were HIV positive and the remaining samples were negative for HIV
      were tested. In the HIV positive group, 44 samples (23.2%) were positive for
      toxoplasma IgG antibody, whilst in the HIV negative group 36 samples (29.5%) were
      positive. All antibody titres found were not higher than 1:64. There is no
      significant difference of toxoplasma IgG antibody in HIV positive and HIV
      negative persons (p = 0.25). Among the HIV positive and T. gondii antibody
      positive group, 19 out of 44 persons (43.2%) had symptoms and signs of acute
      toxoplasmosis involving the eye and/or the central nervous system. Due to the
      high reactivation rate, the authors propose that all HIV-infected persons should
      be tested for T. gondii antibody and prophylactic treatment of opportunistic
      infection from T. gondii should be considered in those with positive results.

PMID- 10932498
TI  - A rice starch added follow-on formula for infants with sleeping difficulty.
AB  - A total of 15 infants aged between 4-12 months with sleeping difficulty were
      enrolled in the study. All participants were given a test follow-on formula
      (cow's milk based), with added rice starch. The test formula was advised to be
      given at night-time for a 7-day period. Sleeping patterns were recorded 2 days
      prior to the study and during the 7-day study period. It was shown than 11 out of
      15 cases (73.3%) had satisfactory results. Two cases (13.3%) were withdrawn from
      the study by their parents due to vomiting after taking the formula. We found
      that both cases developed concomitant respiratory tract infection one day after
      starting the study, and 2 cases (13.3%) were lost to follow-up. In conclusion,
      the majority of cases showed satisfactory results in terms of night sleeping
      pattern after switching to the rice starch added follow--on formula.

PMID- 10932499
TI  - Nutrients and hormones in heat-dried human placenta.
AB  - This cross-sectional study was to assess the nutrients in terms of protein, fat,
      minerals, and hormones in heat-dried human placenta. Thirty heat-dried human
      placentas, 15 from male and 15 from female, were analyzed for protein (amino
      acids), fiber, fat, moisture, minerals (sodium, potassium, phosphorus, calcium,
      iron, magnesium, zinc, copper, manganese), hormones (estradiol, progesterone,
      testosterone, growth hormone). Heat-dried female human placentas had slightly
      higher fiber content than male, but protein and fat components were not
      different. Mineral levels in placentas were high especially sodium, potassium and
      phosphorus. There were no significant differences in the amount of minerals and
      hormonal profile between female and male placentas. However, hormone levels in
      heat-dried placenta were low compared to physiologic level in human beings. The
      results of this study suggest that the amount of nutrients particularly protein
      and minerals in heat-dried human placentas were enriched.

PMID- 10932500
TI  - Bilateral high radial nerve compressions: a case report.
AB  - A 40-year-old woman with bilateral high radial nerve compressions by non
      traumatic cause was reported. It occurred first at the right radial nerve which
      was explored after a period of investigation and conservative treatment. Two
      constricted sites 2.0 cm apart of the right radial nerve crossed by branches of
      the radial collateral artery beneath the lateral head of the triceps were found.
      The constricted sites including tissue in between was resected and replaced with
      a sural nerve graft. One year later the patient had the same episode on the left
      side. The operative finding was the same as the previous one. Sural nerve graft
      was performed after neurolysis had failed. The patient's normal radial nerve
      function returned in one year. This is the first reported case in the literature
      of bilateral high radial nerve compressions by branches of the radial collateral
      artery.

PMID- 10932501
TI  - To tell or not to tell?

PMID- 10932502
TI  - The current therapy of urinary calculi in Thailand.
AB  - The paper analyses the impact of modern therapy of urinary calculi in Thailand
      since the introduction of ESWL and endourology (PCNL and URS) in 1988. Up to
      then, conservative and open surgical measures had been the standard procedures.
      The study covers 12 medical centres in the north, northeast, south and central
      parts of the country between 1988 and 1997. Approximately 40 ESWL machines have
      been in use. ESWL was used in 66.1 per cent and 20.8 per cent of patients with
      renal and ureteric calculi respectively. Only 1.1 per cent of the patients had
      PCNL. URS was used in 20.8 per cent of patients with ureteric calculi. Open
      operations were required in 32.6 per cent and 53.6 per cent of patients with
      renal and ureteric calculi respectively. Nephrectomy was required in 4.8 per cent
      -16.0 per cent of patients with renal calculi. Certain considerations have been
      put forward to appraise the situation concerning urinary stone therapy in
      Thailand.

PMID- 10932503
TI  - Brachial plexus injury and pain: incidence and the effects of surgical
      reconstruction.
AB  - A prospective study of pain after brachial plexus injury was carried out on 246
      patients with at least 2 years follow-up. All of them had closed traction injury
      from motorcycle accidents. There were 16 females and 230 males aged from 16 to 44
      years old. The patients' biodata, onset of pain, characteristics of pain and
      treatment were recorded. Changes in pain after conservative and operative
      treatment and the outcome of treatment were analysed. Two hundred and nineteen
      patients (89%) had significant pain and 182 patients (74%) had severe pain. Most
      of them had continuous pain with 2 to 20 peaks of severe pain per day. Crushing
      type of pain was the most common but mixed type of pain caused the most distress.
      Conservative treatment before surgery could relieve the pain in 39 patients
      (15.8%). Surgical reconstruction could further relieve the pain in 176 patients
      (80.36%). However, 21 patients (8.5%) still had severe pain. Improvement in
      sensory function had more effect on pain reduction than motor function.

PMID- 10932504
TI  - Comparison between mushroom-type and balloon-type gastrostomy buttons.
AB  - The gastrostomy button has been improved rapidly over the last ten years. The
      gastrostomy button was divided into two groups. The first group had a mushroom
      tip and, in this study, the Bard button represented this group. The other had a
      balloon as an internal stabilizer and the Mic-key button represented this group.
      The authors retrospectively studied all buttons inserted at the Royal Children's
      Hospital, Brisbane between 1988 and 1995. The average longevity of Bard and Mic
      key buttons were 378.82 and 259.62 days respectively. Valve incompetence was the
      most common cause of removal of the Bard button (38%), whereas, balloon rupture
      was the major cause of removal of Mic-key button (44%). Each type of gastrostomy
      button had its own advantages and disadvantages and these special characteristics
      will be discussed.

PMID- 10932505
TI  - Bone mineral density of lumbar spine and proximal femur in normal Thai women.
AB  - OBJECTIVE: To find the reference data for age-specific normal bone mineral
      density in a Thai female population. STUDY DESIGN: Cross-sectional, Descriptive
      study. MATERIAL AND METHOD: 1773 Thai women aged between 11-80 years were
      recruited, using multistage cluster sampling and stratifying from six represented
      provinces in the country, each strata was randomly selected. After recruiting,
      the women were interviewed by well-trained personnel using structured
      questionnaires. Bone mineral density of the lumbar spine 1-4 and nondominant hip
      were measured by Dual Energy Photon Absorptiometer. The scientists, X-rays
      technician were trained and standardized inter and intra observers variation.
      Quality control of examination was measured periodically. Every BMD outcome was
      re-examined by a specialist. RESULTS: The peak bone mineral density of both
      spines and hips was between the age of 30 to 34 years old. Mean Value for spine
      and femoral neck was 0.957 and 0.814 g/cm2 respectively. The BMD of spine and hip
      was significantly decreased after the age of 35 and the loss was accelerated at
      age 50. Osteoporosis for spine and femoral neck is considered when BMD are below
      0.682 and 0.569 g/cm2 respectively. CONCLUSION: The results are important data
      for public health policy, by maximizing bone mass during skeletal growth before
      menopause and minimizing bone loss throughout life as well as for detection of
      important risk factors.

PMID- 10932506
TI  - Whole blood agglutination D-dimer test for the diagnosis of deep vein thrombosis.
AB  - Deep vein thrombosis (DVT) is a clinical syndrome the clinical diagnosis of which
      is unreliable and objective tests often require specialized testing facilities.
      The authors examined the diagnostic accuracy of the whole blood agglutination D
      dimer (SimpliRED) test in this condition. Patients who presented with acute onset
      of leg swelling were included in the study. Whole blood agglutination D-dimer
      test was performed upon admission and followed by the gold standard test,
      contrast venography. Forty three patients had venography proven DVT and proximal
      occlusion was found in 31 of them. The sensitivity and specificity of the test
      for DVT were 88.4 per cent and 53 per cent respectively while the positive
      predictive value (PPV) and the negative predictive value (NPV) were 82.6 per cent
      and 64.3 per cent. Interestingly, when focusing the diagnosis on proximal DVT,
      the sensitivity and NPV rose to 100 per cent, whereas, the specificity and PPV
      remained unchanged (48.3 and 67.4%). In conclusion, whole blood agglutination D
      dimer test (SimpliRED) was sensitive but not specific for DVT diagnosis.
      Moreover, when focusing the diagnosis on proximal DVT, the test had excellent
      sensitivity and NPV. This test, therefore, can be an effective screening tool for
      the high embolic risk proximal DVT.

PMID- 10932507
TI  - Investigation of sex chromosome abnormalities in teratozoospermia of infertile
      men using fluorescence in situ hybridization.
AB  - Fluorescence in situ hybridization is a fast and efficient method of
      investigating chromosomal abnormalities in human spermatozoa. In this study, we
      have established the frequency of sex chromosome disomy (XX, XY and YY) in
      teratozoospermia (98-100% abnormal morphology) of infertile men compared with
      normospermic men using double-probe FISH procedures. A total of 40,000 sperms
      were scored in each group of semen for chromosome X and Y with overall
      hybridization efficiency of 97.00 per cent and 98.02 per cent in infertile men
      and normal men, respectively. It was found that the frequency of disomy XX, XY
      and YY was significantly higher in infertile men compared with normal men (P <
      0.05). It is concluded that the infertile men showed increased frequencies of sex
      chromosomal abnormalities.

PMID- 10932508
TI  - Depression in Thai patients with rheumatoid arthritis.
AB  - A wide spectrum of behavioral and psychological disturbances, in particular
      depression, has been described as a prevalent problem in patients with rheumatoid
      arthritis (RA). The investigators proposed to evaluate the correlations of
      depressive symptoms and the disease activity of RA in Thai patients. A variety of
      aspects of disease activity included in the assessment were the number of swollen
      joints, the number of tender joints, overall tenderness of the joints (assessed
      by using the Ritchie Articular Index), overall pain (assessed by using the visual
      analog scale for pain), joint functional class, and disease duration. The 24-item
      Hamilton Rating Scale for Depression (HRSD) was the measure used to determine the
      severity of depressive symptoms. The correlations of HRSD scores and the data
      relevant to the disease activity were evaluated by using Pearson correlation
      test. A total of 75 female and 4 male patients participated in this study. Their
      mean age and mean duration of disease were 49.81 and 7.48 years, respectively.
      The mean score of HRSD was significantly correlated with those of the number of
      swollen joints, the number of tender joints, the Ritchie Articular Index, the
      visual analog scale for pain, and the joint functional class. In conclusion,
      depression is highly correlated with some respects of the disease activity of RA,
      especially the number of swollen joints and joint functional class. The results
      of the present study are not much different from those of previous studies
      conducted in western countries. Careful evaluation of the disease activity of RA
      will be helpful in detecting the depression comorbidity in Thai patients
      suffering from this disease.

PMID- 10932509
TI  - Seizure threshold in electroconvulsive therapy: III. A long-term study.
AB  - There has been a dearth of long-term studies investigating the seizure-threshold
      changes in patients receiving electroconvulsive therapy (ECT). This study aimed
      to determine changes in seizure threshold over acute, continuation, and
      maintenance ECT (Phases I, II, and III). Twenty schizophrenic patients were
      estimated to have a seizure threshold by the dose-titration method. All patients
      had a rise in seizure threshold at the end of Phase I with 185 +/- 196 per cent
      increments. Ten patients had a further threshold-increase at the sixth month
      (Phase II, n = 20), and four at the twelfth month (Phase III, n = 14). The
      overall threshold-increases of Phases II and III were 370 +/- 342 per cent and
      416 +/- 427 per cent, respectively. Seizure-threshold increases were robust
      during acute ECT, and tended to reach a plateau over the continuation and
      maintenance phases.

PMID- 10932510
TI  - Potassium, sodium and magnesium contents in skeletal muscle of renal stone
      formers: a study in an area of low potassium intake.
AB  - Skeletal muscles surgically obtained from the stone-former group (external
      oblique muscle; n = 202, 82 males & 120 females), control group I (external
      oblique muscle; n = 5, all males), control group II (rectus abdominis muscle; n =
      23, all females) and control group III (quadriceps femoris muscle; n = 11, all
      males) were analyzed for potassium (K), sodium (Na) and magnesium (Mg) contents.
      Muscle samples were digested with 65 per cent HNO3 and determined for K, Na and
      Mg by an atomic absorption spectrophotometer. The results of analysis showed the
      mean K, Na and Mg (+/- S.D.) contents in mumol per one gram of fresh tissue of
      the stone-former group, control groups I, II and III were 73.5 +/- 16.6, 51.3 +/-
      13.4 and 6.6 +/- 1.3, 77.5 +/- 3.9, 43.9 +/- 9.9 and 7.2 +/- 0.5, 83.8 +/- 27.5,
      49.4 +/- 24.1 and 6.7 +/- 1.8 and 85.0 +/- 17.1, 48.5 +/- 12.1 and 6.8 +/- 1.3.
      Among these variables, only the K content of control group III was higher
      significantly (p < 0.05) than that of the stone-former group. In the stone-former
      group, regression analysis showed significant correlations between K and Mg
      contents (r = 0.856, p < 0.001) and K and Na contents (r = -0.325, p < 0.001).
      Due to no available data of the external oblique, we made a comparison of our
      results to the soleus type of skeletal muscle of normal subjects reported by
      Dorup et al and found that the external oblique muscle had lower mean contents of
      K and Mg but a higher Na content than those of the soleus. Our results were
      similar to the K and Mg depleted muscles obtained from the patients receiving
      long-term treatment with diuretic drugs. The results suggest that most of our
      subjects in both the stone-former and the 3 control groups were in a state of K
      and Mg depletion. The causes may be multifactorial, for instance low intake, high
      sweat loss and the existence of environmental inhibitor (s) for K transport like
      vanadium.

PMID- 10932511
TI  - Comparison of norgestrel- versus cyproterone acetate-containing hormone
      replacement therapy on lipid-lipoprotein metabolism.
AB  - To compare the effects on the lipid profile of estradiol valerate with norgestrel
      to a regimen of estradiol valerate with cyproterone acetate. Sixty-four healthy
      women in their perimenopause or early postmenopause, aged between 40-55 years,
      were randomized to one of the two 21-day sequential regimens: estradiol valerate
      2 mg/day for 21 days and combined with either norgestrel 0.5 mg/day or
      cyproterone acetate 1 mg/day from day 12 to 21, with 7 days of drug-free
      interval, for 12 cycles. Lipid profiles were followed at baseline, 6 and 12
      cycles. Sixty-one subjects completed the study, 30 in the norgestrel group and 31
      in the cyproterone group. During 12 cycles of study, serum HDL cholesterol levels
      decreased significantly in the norgestrel group (p < 0.01) and were unchanged in
      the cyproterone group. The levels were significantly lower in the norgestrel
      group than in the cyproterone group (p < 0.05). No differences were found between
      groups as regards LDL cholesterol and total cholesterol levels. Triglyceride
      levels decreased significantly in the norgestrel group (p < 0.01), remained
      unchanged in the cyproterone group and the levels were significantly different
      between groups (p < 0.01). In conclusion, the study demonstrated that sequential
      regimen of estradiol valerate with norgestrel produced less favorable HDL
      cholesterol but more favorable triglyceride levels than the regimen of estradiol
      valerate with cyproterone acetate.

PMID- 10932512
TI  - An open, non comparative study of ofloxacin i.v. on the treatment of acute
      symptomatic urinary tract infection.
AB  - The clinical efficacy and the safety of ofloxacin i.v. in 35 acute symptomatic
      urinary tract patients were evaluated. The drug was intravenously administered,
      400 mg starting dose then 200 mg once-daily for 3-5 days. The therapeutic success
      rate and eradication rate in UTI case were 100 per cent in all cases when
      evaluated immediately after completion of drug treatment, therapeutic success
      rate and eradication rate at the follow-up evaluation were 97.2 per cent and 91.6
      per cent respectively. Also, 5 cases of acute bronchitis and 2 salmonellosis were
      also administered intravenously, 400 mg once-daily dose and 400 mg twice daily
      dose respectively. No serious side effects of ofloxacin i.v. therapy were
      observed in any of our patients.

PMID- 10932513
TI  - Topical ciprofloxacin for bacterial corneal ulcer.
AB  - OBJECTIVE: To assess topical ciprofloxacin in patients with moderate severity of
      suspected bacterial corneal ulcers. STUDY DESIGN: Randomized, controlled clinical
      trial. SETTING: Inpatient at Siriraj Hospital. PARTICIPANTS: All patients with
      suspected corneal ulcers. Patients with fungal cause known before admission and
      an allergy to any medication, were excluded. INTERVENTION: Topical ciprofloxacin
      0.3 per cent or cefazolin (50 mg/ml) and fortified gentamicin (14 mg/ml) were
      given every 15 minutes for the first 6 hours, then every half hour on the first
      day, and every hour while awake till midnight until complete recovery without
      staining of fluorescein and no culture growth. MAIN OUTCOME MEASURES: The primary
      outcomes were the success rate and duration of the healing of the ulcer after
      treatment in each group. RESULTS: Forty-one patients were enrolled. Twelve
      (70.6%) of 17 patients in the ciprofloxacin group were therapeutically successful
      while 15 (62.5%) of 24 patients in the control group showed similar outcome
      without a statistically significant difference. However, the mean duration for
      healing after treatment was not significantly different being 14.6 days in the
      control group and 15.6 days in the ciprofloxacin group. Visual improvement in the
      success cases of the control and ciprofloxacin groups was 46.7 per cent, and 66.7
      per cent, respectively. CONCLUSION: Treatment with topical ciprofloxacin in
      suspected bacterial corneal ulcer should be considered as an alternative to
      standard therapy.

PMID- 10932514
TI  - Correlation between serum insulin and features of metabolic syndrome in Thais.
AB  - Several clinical and metabolic abnormalities, i.e. central obesity, hypertension,
      impaired glucose tolerance or diabetes and dyslipidemia often cluster together
      and are commonly found in patients with atherosclerotic cardiovascular disease.
      Hyperinsulinemia and insulin resistance are often evident in subjects with these
      metabolic abnormalities, so called insulin resistance or metabolic syndrome. In
      the present study, we looked into the correlations between serum insulin or index
      of insulin sensitivity and various clinical and metabolic abnormalities. Subjects
      consisted of 103 males and 118 females. Oral glucose tolerance test was performed
      on all subjects. Homeostasis model assessment of insulin sensitivity (HOMA-S) was
      used to determine insulin sensitivity. In males, HOMA-S was found to be
      significantly correlated with BMI, plasma glucose, insulin, triglycerides and
      waist circumference. Male subjects in the highest quartile of HOMA-S also had
      significantly higher systolic blood pressure compared to those in the lowest
      quartile. In females, HOMA-S was significantly correlated with BMI, blood
      pressure, plasma glucose, insulin, triglycerides, HDL-cholesterol, waist
      circumferences and waist-hip ratio. However, after adjustment for BMI,
      correlation between HOMA-S and blood pressure in women was no longer
      statistically significant. We, therefore, concluded that correlations between
      serum insulin or index of insulin sensitivity with certain metabolic
      abnormalities also existed in Thai subjects. Some of these correlations seem to
      be at least in part dependent on obesity.

PMID- 10932515
TI  - Different reticulocyte volume in diabetes mellitus patients with and without
      hypercholesterolemia and/or hypertriglyceridemia.
AB  - Red cells and reticulocytes from patients with diabetes mellitus (DM) were
      analysed using laser and computer technology of H*3 hematology analyzer. Four
      groups of diabetes mellitus patients: diabetes with normolipemia (DM) (n = 12)
      and DM patients with excess triglyceride (DM-T) (n = 7) or cholesterol (DM-C) (n
      = 21) or both (DM-TC) (n = 21) were studied. Mean corpuscular volume of mature
      red cells (Mean +/- SD = 93.6 +/- 5.5 fl) and reticulocyte (119.1 +/- 12.3 fl) of
      patients with DM-T was not significantly increased from normal (red cell, 90.0 +/
      3.5 fl; reticulocyte, 115.2 +/- 7.3 fl). Plasma triglyceride levels had no
      significant correlation with red cell MCV, reticulocyte MCV and %Hb A1c. This
      suggests that high triglyceride levels in DM are not dose-dependent in producing
      increased MCV of red cells and reticulocytes. Comparing between DM-T and DM-C,
      red cells and reticulocytes from DM-C patients had significantly decreased MCV
      (red cell, 85.5 +/- 6.1 fL; reticulocyte, 103.8 +/- 7.4 fL). Plasma cholesterol
      levels were inversely correlated with MCV of red cells (r = -0.377, p = 0.003)
      and also MCV of reticulocytes (r = -0.418, p = 0.001). In addition, cholesterol
      levels showed considerable correlation with Hb A1c (r = 0.572, p = 0.004). The
      red cell volume change in DM-C patients may be partly due to the shift in balance
      of cholesterol exchange between red cell membranes and serum lipoproteins.

PMID- 10932516
TI  - The utility of conventional dipsticks for urinary protein for screening of
      microalbuminuria in diabetic patients.
AB  - The demonstration that microalbuminuria is predictive of overt diabetic
      nephropathy has created a demand for the routine measurement of urinary albumin
      in diabetic patients. We assessed the sensitivity, specificity, positive and
      negative predictive values of the conventional dipsticks for urinary protein
      (Ames Multistix, Bayer Diagnostic, Australia) as the screening test for
      microalbuminuria in diabetic patients compared with Micral-Test II (Boehringer
      Mannheim, Germany). Radioimmunoassay for albumin was taken as standard for
      comparison. With the urinary albumin concentration of 20 mg/L as a discriminating
      level of microalbuminuria, Micral-Test II had a sensitivity of 98.8 per cent and
      a specificity of 68.6 per cent whereas Ames Multistix had lower sensitivity but
      higher specificity. If urinary albumin concentration of 60 mg/L was used instead
      as a discriminating level of microalbuminuria, none of Ames Multistix by visual
      reading and only 5 of 32 (15.6%) of those by reflectance photometer had false
      negative results. By visual reading, the sensitivity of Ames Multistix was
      increased from 68.1 to 100 per cent with the drop in specificity from 85.7 to
      50.2 per cent. On the other hand, the sensitivity was increased from 37.4 to 84.4
      per cent but the specificity was maintained if reflectance photometer was used.
      In conclusion, Ames Multistix was less sensitive than Micral-Test II in detection
      of urinary albumin concentration above 20 mg/L. At higher urinary albumin
      concentration above 60 mg/L which indicates a clinically significant
      microalbuminuria, the sensitivity of Ames Multistix was increased to 100 per
      cent. Ames Multistix which is much less expensive than Micral-Test II, can be
      used as the screening test for significant microalbuminuria in clinical practice
      particularly in cases having financial problems.

PMID- 10932517
TI  - Left-sided gastroschisis: two case reports in Ratchaburi Hospital.
AB  - Left-sided gastroschisis has rarely been reported. From August 1987 to April
      1998, 73 cases of gastroschisis were treated at the Pediatric Surgical Unit,
      Department of Surgery, Ratchaburi Hospital. The abdominal wall defect of only 2
      cases occurred on the left side of the umbilicus. The 2 cases of left-sided
      gastroschisis were girls and were successfully treated by primary fascial
      closure. After 7 and 1 year follow-up the patients remain asymptomatic.

PMID- 10932519
TI  - Teaching ethics for medical students.

PMID- 10932518
TI  - Fibrolamellar hepatocellular carcinoma in a Thai man who presented with
      hypoglycemia: case report and review of literature.
AB  - We present a case of fibrolamellar hepatocellular carcinoma (FLHCC) in a 22 year
      old Thai man whose presenting symptom was hypoglycemic coma with right
      hemiparesis. The serum marker for hepatitis B virus (HBsAg) was positive and
      serum AFP was very high (over 100,000 IU/ml). The abdominal ultrasonography
      revealed a solitary heterogenic mass, size 5.5 x 6.5 cm in the right lobe. Chest
      X-ray showed multiple lung metastases. Ultrasound-guided needle liver biopsy was
      performed and typical histologic features of FLHCC in non-cirrhotic liver were
      diagnosed. The patient's comatose state and neurological deficits recovered
      rapidly after glucose administration. Unfortunately, the tumor mass could not be
      resected on account of far-advanced stage with metastases. Here, we also review
      of the literature concerning FLHCC in many aspects.

PMID- 10932520
TI  - Noninvasive estimation of the end systolic pressure-volume relationship using
      impedance cardiography.
AB  - PURPOSE: Traditional measures of cardiac contractility such as dp/dt and ejection
      fraction has been noted to be sensitive to preload and afterload conditions. The
      end systolic pressure-volume relationship of the left ventricle (ESPVR, Suga
      Index or Emax) has been found to be the best load independent measure of the
      cardiac contractile state. However, determination of the ESPVR requires very
      highly invasive procedures. Impedance cardiography (IC) is a reliable noninvasive
      method for calculating stroke volume and may also be useful for estimating the
      end systolic volume. METHODS: An equation was derived using the systolic time
      intervals (PEP = pre-ejection period, LVET = left ventricular ejection time) and
      determined stroke volume (SV) as calculated from the impedance cardiograph to
      estimate the end systolic volume of the left ventricle. Likewise, and systolic
      pressure (ESP) was estimated from brachial cuff pressures using a previously
      published method. The resulting ESPVR was then calculated from tracings recorded
      in healthy normal subjects and compared to those obtained from patients in
      decompensated congestive heart failure (ejection fraction < 30% by
      echocardiogram) using the standard t test (p < 0.05). RESULTS: Using the derived
      equation (ESPVR = ESP/(SV/(1.125-1.25(PEP/LVET)) - SV), the ESPVR for the normal
      group of 6 averaged 2.72 +/- 0.71 and was significantly different from the 1.04
      +/- 0.45 found in 6 patients with known systolic dysfunction. In a further test
      of the method, 15 patients who received concurrent echocardiographic and IC
      evaluations were found to have calculated ESPVR values that significantly
      correlated with determined ejection fractions (r = 0.83, p < 0.01). CONCLUSIONS:
      A noninvasive method for estimating the ESPVR that differentiates the myocardial
      contractile state in the clinically setting was derived using parameters obtained
      from IC. While further studies are needed to correlate this new equation with
      invasive measurements, this method has the potential for easily estimating load
      independent contractility in patients with cardiac dysfunction.

PMID- 10932521
TI  - Utilization of parenteral nutrition in patients receiving peripheral blood stem
      cell transplantation.
AB  - A paucity of information is available on the use of parenteral nutrition (PN) in
      patients undergoing peripheral blood stem cell transplantation (PBSCT). To
      characterize the utilization of PN in patients undergoing PBSCT, we conducted a
      retrospective chart review study on adult patients receiving autologous and
      allogeneic PBSCT. Data collection included nutritional parameters such as
      indications for PN, days of PN administration, and PN-associated complications
      (i.e., metabolic, infectious, and mechanical). Outcome parameters assessed
      included length of hospitalization, days to engraftment, graft versus host
      disease (GVHD), and veno-occlusive disease (VOD). A total of twenty-one
      consecutive patients were evaluated with 12 receiving allogeneic PBSCT and 9
      receiving autologous PBSCT. The allogeneic group received PN for a mean of 25
      days compared to 21 days for the autologous group. The rate of metabolic
      abnormalities was significantly higher in the allogeneic group compared to the
      autologous group (1.02 abnormalities/PN days vs 0.61 abnormalities/PN day, p <
      0.05), but mechanical and infectious complications were similar between the two
      groups. Length of hospitalization, days to engraftment, incidence of GVHD and VOD
      did not differ significantly between the two groups. However, mortality prior to
      discharge was significantly higher in the allogeneic vs autologous group (58% vs
      0%, p < 0.05). We conclude that allogeneic PBSCT patients appear to be at a
      greater risk for metabolic complications while receiving PN as compared to
      autologous PBSCT patients. As nausea and vomiting are two primary reasons for
      initiation of PN in this patient population, further studies of aggressive
      antiemetic therapy may prove to decrease the need for PN in PBSCT patients.

PMID- 10932522
TI  - The effect of acute restraint stress on regional brain neurotransmitter levels in
      stress-susceptible pietrain pigs.
AB  - Concentrations of noradrenaline (NA), adrenaline (A), dopamine (DA), 5
      hydroxytryptamine (5-HT), the DA metabolites 3,4-dihydroxyphenylacetic acid
      (DOPAC) and homovanillic acid (HVA) and the main 5-HT metabolite 5-hydroxyindole
      3-acetic acid (5-HIAA) were measured using HPLC in 16 brain areas of control and
      immobilized Pietrain pigs. The animals were immobilized for 15, 30 and 60 min in
      the prone position. Control pigs showed patterns of regional distribution of
      brain monoamines similar to those described for rats, dogs and Duroc pigs.
      However, the absolute values of NA and A in the hypothalamus and preoptic area
      were much higher than those in rats and dogs, but similar to those in Duroc pigs.
      The concentrations of dopamine and its metabolites DOPAC and HVA were highest in
      the caudate nucleus, the nucleus accumbens, the olfactory tubercle and the
      ventral tegmental area. The distributions of serotonin and its metabolite 5-HIAA
      were similar in all examined structures. DOPAC/DA and HVA/DA ratios were higher
      in the cornu ammonis, the hippocampus posterior and the raphe nuclei than in
      other structures, which suggests brain structure-related differences in dopamine
      turnover. The greatest decreases in NA and A content were observed in the
      hypothalamus, the preoptic area and the olfactory tuberculum during the first 30
      min of immobilization stress. 5-HT turnover was increased in the raphe nuclei,
      while DA turnover was affected in the raphe nuclei, the septum, the substantia
      nigra and the olfactory tubercle. We suggest that acute immobilization stress
      caused differences in regional patterns of brain biogenic amines, thereby
      maintaining adequate transmitter levels during stress in stress-susceptible pigs.

PMID- 10932523
TI  - Reproductive efficiency of three estrus synchronization schemes comprising fixed
      time insemination in dairy cows.
AB  - The objective of this field trial was to compare the odds of pregnancy at 25 days
      (P25) and at 60 days (P60), of embryonic death (ED) between 25 and 60 days, and
      of non-pregnant cows returning to heat 20-25 days after artificial insemination
      (AI). Three fixed-time insemination protocols involving combined administration
      of either double gonadotrophin-releasing hormone (GnRH) and prostaglandins (A) or
      GnRH, human chorionic gonadotrophin (hCG) and prostaglandins (B), or double
      treatment with prostaglandins (C) were used. Cows included in the trial were
      selected from five herds, comprising a total of 735 (herd size range 85-250,
      median 120) Holstein dairy cows. Animals used for the study were multiparous, 4-7
      years of age, had expressed at least one overt postpartum heat, were between 60
      and 120 days of lactation and had at least one palpable corpus luteum and no
      gross morphological anomalies of their reproductive tracts. They were randomly
      allocated to receive treatment A (n = 89), B (n = 93), or C (n = 65). Pregnancy
      of cows not observed in heat 18-24 days post AI was diagnosed by transrectal
      ultrasonography at 25-30 days and confirmed by rectal palpation at 60-75 days
      post AI. Those that were detected in heat in the normal period post AI were re
      inseminated. No differences were detected among the three treatment groups
      concerning the odds of P25 (P = 0.5), P60 (P = 0.2) and ED (P = 0.13). In
      contrast, non-pregnant cows that were administered treatment A were less likely
      to exhibit estrous signs in the normal period post AI than those administered
      treatments B (P = 0.02) or C (P = 0.005).

PMID- 10932524
TI  - Comparative electrocardiography in four species of macaws (genera Anodorhynchus
      and Ara).
AB  - Electrocardiograms (ECGs) were recorded during isoflurane anaesthesia from 52
      macaws of four species of the genera Anodorhynchus and Ara in order to establish
      electrocardiographic reference values. The birds examined were clinically healthy
      macaws of the following species: hyacinth macaw (HM; Anodorhynchus hyacinthinus,
      n = 14); green-winged macaw (GWM; Ara chloroptera, n = 11); blue-throated macaw
      (BTM; Ara glaucogularis, n = 15); and red-fronted macaw (RFM; Ara rubrogenys, n =
      12). All ECGs were recorded using a paper speed of 50 mm/s and a calibration of
      10 mm = 1 mV. Significant differences were determined between species for the
      heart rate, duration and amplitude of the P wave, amplitude of the T wave, and
      amplitude of the QRS complex, specially comparing the RFM to the other macaw
      species. No significant differences were found between two species of similar
      body weight: the HM and the GWM.

PMID- 10932525
TI  - Mechanical factors affecting the occurrence of intervertebral disc calcification
      in the dachshund--a population study.
AB  - In a population sample comprising 48 standard wirehaired dachshunds, the
      occurrence of intervertebral disc calcification was determined by plain spinal
      radiography. Body dimensions of the dogs were measured and information obtained
      from owners about exercise patterns, including stair climbing, and the relation
      of these variables to the number of calcified discs was analysed by logistic
      regression. In the Danish population of wirehaired dachshunds, the prevalence of
      disc calcification was estimated at 77%. The spinal distribution of calcified
      discs is similar amongst different populations, while the prevalence varies
      significantly. Most types of exercise included in the variable 'duration of
      exercise' as well as moderate stair climbing seemed to reduce the rate of
      occurrence of disc calcification. The effects of moderate stair climbing (OR =
      0.34) and duration of exercise (OR = 0.52) were statistically significant and the
      effects appear to be additive. Running next to a bicycle was the only type of
      exercise with a positive association with the number of calcified discs. This
      was, however, not significant. Effects of body conformation, including absolute
      and relative body measurements, were not found.

PMID- 10932527
TI  - The effectiveness of the haemodialysate Solcoseryl for second-intention wound
      healing in horses and ponies.
AB  - Second-intention healing of limb wounds in horses is often problematic.
      Solcoseryl is a protein-free, standardized dialysate/ultrafiltrate (HD) derived
      from calf blood, which has been shown to improve healing in both animals and
      humans. The efficacy of HD in the healing of deep wounds in horses and ponies was
      investigated. Deep wounds of 20 by 35 mm were created on both metatarsi (skin,
      subcutis, periosteum) and on both femoral biceps muscles (skin, subcutis, muscle)
      of five horses and five ponies. The wounds on one side were treated with HD, four
      times a week during the period that the wounds were bandaged and once daily
      thereafter. The wounds on the other side were left untreated. In the first 4
      weeks of the healing period HD stimulated healing but inhibited healing
      thereafter. This pattern was significant for all wound groups (P < 0.001).
      Because of this change in effect, the overall effect on wound healing over the
      entire period was not significant (P = 0.77). HD stimulated healing initially by
      provoking a greater initial inflammatory response, faster contraction and faster
      formation of granulation tissue. Subsequently, HD inhibited healing because it
      significantly delayed epithelialization and caused protracted inflammation. The
      effects of HD were most pronounced in the horses. Because this study
      distinguished between contraction and epithelialization, it could be shown that
      HD stimulated contraction but inhibited epithelialization. Therefore, HD is
      useful in horses for the treatment of deep wounds during the initial phase of
      healing by second intention, i.e. during the first weeks when wound contraction
      can be expected. Treatment should be ceased when epithelialization becomes
      predominant.

PMID- 10932526
TI  - Polyamines in the gastro-intestinal tract of goat kids and in the regenerating
      ruminal epithelium of sheep.
AB  - The aim of the present study was to investigate whether temporal changes in
      polyamine concentration and synthesis could be found in the luminal content and
      wall tissue of the rumen and abomasum, two organs which have entirely different
      growth patterns during the first month of life. In the abomasal mucosa there was
      a marked gradual decrease in the ornithine decarboxylase (ODC) activity during
      the first month of life, while the ODC activity in the ruminal mucosa was low
      during the whole experimental period. However, injury of the rumen wall was
      followed by increased ODC activity. The ODC activity in duodenal mucosa was about
      10 times higher than in the ileal mucosa and the ruminal epithelium. In ruminal
      liquid a clear peak in ODC activity was observed during the period 51-70 days
      after birth. The polyamine concentration did not parallel the ODC activity, in
      either the ruminal epithelium or the ruminal liquid. Of the polyamines, the
      spermine concentration was always highest, and with the exception of duodenal
      mucosa, the putrescine concentration was lowest. In liver a clear decrease in
      spermidine concentration from day 1 to about day 60 after birth was observed.
      Otherwise no marked temporal changes in tissue polyamine concentrations were
      observed. Two and a half hours after oral administration of 14C-labelled
      spermine, nearly all of the radioactivity was found in the lumen of the
      gastrointestinal tract. On the other hand, 1 h after intravenous injection of
      polyamines the walls of the gastrointestinal tract were strongly labelled. In
      conclusion, the polyamines needed for ruminal epithelial development seem to come
      from sources other than the ruminal epithelium itself or the ruminal lumen.

PMID- 10932528
TI  - [Malaria in Croatia: in the past, today and tomorrow].
AB  - Until 1964, when officially declared eradicated, malaria had been a major public
      health problem in Croatia. No autochthonous infections have been noted since
      1958. Within ten year period after the eradication three cases were transmitted
      by transfusion. Until 1998, all other cases, a total of 308, were imported.
      Within last 10 years 119 cases were noted. The most of infections were caused by
      P. falciparum (n = 71, 59.66%), than by P. vivax (n = 31, 26.05%), and P. ovale,
      respectively (n = 1, 0.84%). Mixed infections were noted in 8 cases (6.73%), and
      the cause remained undetermined in 6 (1.68%). Seamen make the most of those who
      acquire primary malaria. There are some 30,000 seamen in Croatia. Some 10,000 are
      on foreign ships, therefore many data are definitely not available or incomplete.
      An average of 8 Croatian seamen get infected annually, but this number is
      supposed to be much greater. Mosquitos which are vectors for malaria exist in
      Croatia even today. Sporadic cases of autochthonous malaria in the neighboring
      countries, in which malaria was officially eradicated, are a warning that cases
      of autochthonous malaria might appear in Croatia, too. Due to the increased
      resistance to known antimalaria drugs including mefloquine, chemoprophylaxis when
      indicated, campaign against mosquitos, and control of persons who come from the
      malaria regions are determinants of control of malaria in Croatia, as in
      accordance with World Health Organization recommendations. Besides, further
      research of medically interesting insects, including the genus Anopheles, would
      be useful, at least in the coastal area of Croatia.

PMID- 10932529
TI  - [Family practitioners in the primary health care of preschool-age children--a
      report on well-child care in the practice of 2 family medicine physicians].
AB  - Primary health care of preschool children is organized in the Republic of Croatia
      by pediatricians, general practitioners and family/general practice specialist.
      The aim of this study is to evaluate the care for preschool children in the well
      baby clinics led by general/family specialist. Vaccination and visits data were
      collected from the medical records of 148 children born from January 1st 1992
      till December 31st 1997, registered in two family practice offices in the well
      baby clinics at the Dugave-Travno Health Station of the "Novi Zagreb" Health
      Center. Comparison was made between data on compulsory immunization minimum in
      the Republic of Croatia and data from the Croatian National Institute of Public
      Health on vaccination of infants and preschool children in the Republic of
      Croatia in 1997. Diphtheria, tetanus and poliomyelitis vaccination was 100%,
      pertussis vaccination was 97.2%, measles and parotitis vaccination was 92.2% and
      rubella vaccination was 91.5%. Diphtheria and tetanus revaccination of children
      in the second year of life was 97.6%, pertussis revaccination was 94.4% and
      poliomyelitis revaccination was 96.8%. Comparison of those results proves the
      efficacy of compulsory immunization program of preschool children in
      family/general specialists' offices. The accessibility of general/family
      practice, appropriate education of general/family specialists during the
      specialization in family medicine for primary care of preschool children as well
      as for other family members, the ability of family physician to offer integrated
      continuous care and good cooperation of the family physician and the public nurse
      are the factors that enable appropriate primary care for preschool children in
      general practice/family medicine.

PMID- 10932530
TI  - [Specifics of health services utilization in an affiliated ambulatory general
      medicine practice].
AB  - Rationalisation in primary health care includes solutions such as affiliated
      practices. This study tries to detect specific utilisation of affiliated
      practices. The survey was done in general practice setting Bukovlje and
      affiliated practice Klokocevik, both near Slavonski Brod. A three-month
      prospective study using the International Classification of Primary Care was
      done. The results showed no difference in morbidity. The number of visits per
      patient was 1.29 in the main practice and 1.06 in the affiliated practice. The
      average number of reasons for encounter per one visit was 1.6 in the affiliated
      practice and 1.37 in the main practice. Symptoms and complaints, as well as
      referrals were more frequent reasons for encounter in the main practice (28% vs.
      20%, and 15% vs. 10%). In spite of a similar morbidity, users of the affiliated
      practice less frequently utilised health care, inclined to postpone their visit
      to the doctor and refused referrals. The observed type of health care utilisation
      could present a health risk.

PMID- 10932532
TI  - [Aspiration of foreign bodies in the bronchi in children].
AB  - Records on 28 children (19 boys and 9 girls), mean age 3.1 years (range 6 months
      to 11 years), treated for foreign body aspiration (FBA) at the Department of
      Pediatrics, Split Clinical Hospital, during the 1992-1997 period, were analyzed.
      The mean hospital stay was 12.3 days (range 1 h to 92 days). History data on
      tracheobronchial FBA were available in 23 (82%) children. Radiologic findings
      pointed to FBA in 22 (77%) children. Rigid tracheobronchoscopy was performed in
      all patients, and proved successful in 26 (93%) of children. Digestible foreign
      bodies and food particles were removed in 22 (78%) children. Right-sided and left
      sided bronchial FBA was recorded in 14 (50%) and 13 (46%) patients, respectively,
      whereas bilateral obstruction was present in one patient. The importance of
      suspected FBA in children with pronounced symptoms of coughing, dyspnea and choke
      is emphasized. Rigid tracheobronchoscopy and foreign body removal by forceps
      under anesthesia is an efficient and safe method, and we recommend its wider use
      in clinical practice.

PMID- 10932531
TI  - [Foreign bodies in the airways in children].
AB  - From 1984 to 1998 we treated 22 children (15 male, 7 female) with aspirated
      foreign bodies in their tracheobronchial tree. Most patients (17/22, 77%) were
      aged up to 3 years (two children were seven months old). Only 12 (54%) patients
      had history of aspiration. Most common clinical findings were prolonged
      expiration and impaired respiration on one side (12 patients, 54%) or impaired
      respiration on one side (7 patients, 32%). Chest x-rays mostly showed one-sided
      hyperinflation (64% of cases). 50% of children aspirated walnut into their
      airways. Foreign bodies in most children were installed tracheobronchially on the
      left and right side and in one child the foreign body was found in the larynx.
      The foreign bodies were successfully removed in 19 (85%) patients. In three
      children foreign bodies were not found on time, bronchial obliteration occurred,
      so pulmectomy of the left lung, lobectomy of the left lower lobe, or bilobectomy
      (lower and middle right lobe) had to be done.

PMID- 10932533
TI  - [Choledochal cysts: surgical treatment].
AB  - The excision of the choledochal cyst with bile drainage through intestinal
      conduit is a standard operative procedure in the surgical management of
      choledochal cysts. During the last eight years five patients have been treated
      with this operation at the University Children's Hospital in Zagreb. All the
      patients were girls aged from two months to twelve years. The classical triad of
      pain, jaundice and abdominal mass was observed in only one patient, an eight-year
      old girl. The only symptom in infancy was jaundice. Diagnosis was made by
      abdominal ultrasound, bibliography, CT scan with hepatotropic contrast and in
      older children by ERCP. Four cysts were type Todani I, and one cyst was Todani
      type II. The complete excision of the choledochal cyst with the Roux-Y jejunal
      conduit without antireflux valve was performed. There was neither operative
      morbidity nor mortality. Three months postoperatively the control ultrasonography
      and liver laboratory tests were without abnormalities. The routine control which
      followed did not show episodes of cholangitis, lithiasis, lipid malabsorption,
      blood clotting abnormalities or growth failure. The complete excision of the cyst
      with Roux-Y hepaticoenterostomy is an operative treatment with good results in
      infancy and childhood.

PMID- 10932534
TI  - [The role of zinc in the initial treatment of Wilson's disease in children].
AB  - Wilson's disease (WD) is an inherited disease of copper accumulation, caused by a
      failure of biliary excretion of excess copper. Accumulated copper causes tissue
      damage. The chelating drugs penicillamine and trientine have been the mainstay of
      therapy and most patients with WD were treated with the potentially toxic
      cupriuretic agents. A more recent approach has used zinc, which blocks the
      absorption of copper and increases copper excretion in the stool, and long term
      administration induces a negative copper balance. Until recently, most patients
      have been treated initially with cupriuretic agents to remove excess of copper,
      and then maintained with oral zinc. Recently, zinc has been used for initial
      treatment as well and for treatment of the presymptomatic patients. So far, zinc
      therapy has demonstrated exceptional efficacy and lack of toxicity. In this
      article we present our data on the long-term follow-up of three children with WD,
      whose initial as well as consecutive treatment was zinc sulphate. The results
      demonstrate the efficacy of zinc therapy in treating the presymptomatic patient
      and in initial treatment of symptomatic children with WD. Our data also indicate
      low toxicity. However, pediatric patients must be closely monitored due to
      tendency to stop the treatment when becoming asymptomatic.

PMID- 10932536
TI  - [Wilson's disease revisited].

PMID- 10932535
TI  - [Fetal hypoxia--etiology and pathophysiology of hypoxic damage].
AB  - In current perinatology, the prevention of hypoxic damage to the organs, brain in
      particular, is given special emphasis. The causes of fetal hypoxia include
      maternal (preuterine), intrauterine, umbilical, placental and fetal causes.
      Hypoxia and hypoxic lesions occur prenatally in about 80%, and perinatally in 10
      20% of cases. Hypoxia/ischemia induce cellular and subcellular responses in the
      fetal brain. Some of these are membraneous phenomena such as potassium channel
      activation, enhanced release of excitoxic amino acids aspartate and glutaminate,
      activation of NMDA receptors, transmembranous calcium ion influx, and membranous
      lipid peroxidation. Cytosolic events include the formation of free oxygen
      radicals, release of eicosanoids, prostaglandins, leukotriens and cytokines,
      enzyme activation, and gene induction.

PMID- 10932537
TI  - [The conditions for the germination of basidiomycete spores to obtain monosporic
      cultures].
AB  - Spore germination conditions of Basidiomycetes in a culture have been studied.
      Data about influence of some mineral salts, vitamins and sources of carbon on
      stimulation of quantity of germinating basidiospores are presented. Optimum
      conditions to obtain monosporous cultures from separate germinating basidiospores
      are analyzed in the paper.

PMID- 10932538
TI  - [The effect of ethanol on the fatty acid content of Saccharomyces cerevisiae and
      Schwanniomyces occidentalis cells].
AB  - The influence of ethanol on fatty acid content in the cells of the Crabtree
      positive yeast Saccharomyces cerevisiae and Crabtree-negative Schwanniomyces
      occidentalis has been studied. It was shown, that S. cerevisiae grown in the
      medium with 2% glucose was characterized by the lower level of fatty acids in
      comparison with Schw. occidentalis, while in the medium with 1.5% ethanol no
      significant difference was found between the contents of fatty acids in the cells
      of the yeasts investigated. The level of fatty acids in S. cerevisiae is reduced,
      but that in Schw. occidentalis is enhanced when ethanol was added to the medium
      containing 2% glucose. The growing of both yeast species in the medium with 0.1%
      glucose and ethanol leads to the increase of the amount of esterified fatty
      acids. The level of nonesterified fatty acids increased in Schw. occidentalis and
      decreased under the same conditions in S. cerevisiae. However, the content of
      nonesterified fatty acid in S. cerevisiae grown in the medium with 0.1% glucose
      and 1.5% ethanol was 6.2 times higher as compared with those growing in the
      medium containing 2% glucose and 1.5% ethanol.

PMID- 10932539
TI  - [The molecular-weight characteristics of the bacterial lectins and humus
      components in soil].
AB  - A method has been developed to determine the molecular-weight distribution of
      biologically active substances: bacterial lectins and soil humus compounds. The
      method based on the simultaneous centrifugation of samples and molecular weight
      standards in the density gradient of NaCl solutions or combined gradient of NaCl
      and CsCl solutions permits analysing biologically active substances: lectins,
      proteins, polysaccharides, protein-polysaccharide complexes, humus compounds in
      the interval of molecular weight of 13.7 kappa [symbol: see text] a to 2000 kappa
      [symbol: see text] a. The use of this method in the soil researches makes it
      possible to study the dynamics of change of molecular parameters of the soil
      organic matter depending on agrotechnical methods as well as to determine
      transformation regularities of microbial polysaccharides.

PMID- 10932540
TI  - [The effect of antibiotic preparations and their combinations with probiotics on
      the intestinal microflora of mice].
AB  - Antibiotic drugs (biseptol, polymyxin, canamycin) as well as their combinations
      with probiotics biosporin and subalin have been studied for their effect on mice
      intestine microflora. It has been established that under peroral administration
      of the above drugs dysbacteriosis of the 2-3rd degrees arises in animals; under
      their combined use with probiotics one can prevent the development of
      dysbacteriosis to considerable extent. It has been shown that dysbacteriosis of
      the 2-3rd degrees can be liquidated for 5-7 days, using probiotics biosporin and
      subalin. No self-recovery of normal intestinal microbiocenosis is observed in
      this period. Inconsiderable variations in the composition of normoflora under
      combined use of antibiotics with probiotics are renewed on the 3-5th day after
      stopping the drugs intake.

PMID- 10932542
TI  - [The antibiotic sensitivity of microorganisms isolated from newborn infants].
AB  - Bacterial strains (219) isolated from newborn children were studied for their
      sensitivity to 17 antibiotics. In the case of the species studied the increase of
      resistance to cephalothin, cefazolin, cefotaxime, ceftriaxone, gentamicin,
      tobramycin, chloramphenicol by 5.7 to 43% was found. This evidenced for a
      necessity to revise the tactics of their further use for treatment and
      prophylaxis, while the identification of the strains resistant to ofloxacin and
      ciprofloxacin evidenced for the appearance of new resistance determinants. The
      high level of resistance to antibiotics and practically identical profile of
      antibiotics in the strains isolated from newborns and epidemiologically
      significant environmental objects in the examined hospitals do point to possible
      colonization of newborns by the hospital strains.

PMID- 10932541
TI  - [The effect of biostimulants and fungicides on the growth parameters of natural
      associations of soil microorganisms].
AB  - Biostimulants ivin and emistym take positive effect on the growth characteristics
      of natural association of soil microorganisms: they increase the specific growth
      rate, the number of generations, decrease the lag-phase and duration of
      redoubling the number of microorganisms. Presence of fungicides in the medium
      inhibits the growth of microorganisms. Under combined use of biostimulants and
      fungicides one cannot reveal the negative effect of fungicides on the natural
      associations of microorganisms, however the stimulating action of growth
      regulating substances decreases.

PMID- 10932543
TI  - [AF, a new bacterial preparation based on lactobacilli and its biological
      properties].
AB  - A highly efficient bacterial composition "AF" which includes representatives of
      two genera of microorganisms Enterococcus faecium and Lactobacillus acidophilus
      has been created as a result of analysis of biological properties of a number of
      strains of lactic-acid bacteria. Their biological properties--antagonistic
      activity in respect to pathogenic and conditionally pathogenic microorganisms,
      ability to adhesion and function in the intestine, sensitivity to antibiotics,
      etc., have been studied in the laboratory conditions. Prospects of the use of the
      given composition in production of milk products of functional effects have been
      shown.

PMID- 10932544
TI  - [The intensification of biological nitrogen fixation by using ammonium carbonate
      compounds and the routes of their action on microorganisms and plants].
AB  - The intensification of activity of associative and symbiotic nitrogen fixation
      while using low amounts of ammonium-carbonate compounds, carbonic-ammonium salts,
      in particular, has been established. The main ways and mechanisms of the action
      of ammonium-carbonate salts as a new and perspective agrochemical on
      physiological and biochemical processes of microorganisms and agricultural plants
      were presented on the basis of the analysis of literary information and the
      author's investigations.

PMID- 10932545
TI  - Learning from our mistakes.

PMID- 10932546
TI  - Preventing medical errors. A blueprint for safety.

PMID- 10932547
TI  - Error prevention: one state's approach.

PMID- 10932548
TI  - Physicians can help implement 'culture of safety'.

PMID- 10932549
TI  - Error in medicine: what have we learned?

PMID- 10932550
TI  - Tattoos: their relationship to trauma, psychopathology, and other myths.
AB  - OBJECTIVE: The purpose of this study was to examine the relationship between
      tattoos and reason for presentation to a community hospital emergency department
      (ED): injury, illness, or a psychiatric/chemical dependency problem. In addition,
      to assess contemporary beliefs about tattoos, ED staff and patients were surveyed
      about their attitudes toward and personal experience with tattoos. Demographic
      characteristics of participants also were evaluated relative to tattoos. METHODS:
      All patients seen in the ED during two 24-hour periods in winter 1999 were
      surveyed about tattoos in a personal interview. Hospital staff who regularly
      interact with ED patients were asked the same questions. Data were collected on
      294 patients and 289 staff members. Diagnoses were recorded for all patients,
      then coded as an injury, illness, or psychiatric/chemical dependency complaint.
      RESULTS: In the 16-35 years age group, 35% of patients and 19% of staff had
      tattoos. In the 36-50 years age group, 28% of patients and 11% of staff had
      tattoos, and the 51-65 group had similar percentages: 6% of patients and 5% of
      staff had tattoos. Having a tattoo was not related to presenting complaint. Age
      was a significant predictor of attitudes regarding tattoos: Younger people had a
      more positive attitude. Significantly more smokers (31%) than nonsmokers (13%)
      had tattoos. Education was negatively related to having a tattoo. Gender was not
      significantly related to having a tattoo or to the number of tattoos a person
      had. CONCLUSION: A surprisingly large percentage of young patients presenting to
      the ED had tattoos. No relationship was found between having a tattoo and nature
      of chief complaint.

PMID- 10932551
TI  - Managing risk.

PMID- 10932552
TI  - Opening the National Practitioner Data Bank. Good idea or bad public policy?

PMID- 10932553
TI  - In Minnesota clean air debates, where there's smoke, there's ire.

PMID- 10932554
TI  - The Cochrane Library: a resource for current reviews of clinical evidence.
AB  - The Cochrane Library is a tool for physicians and other health care practitioners
      seeking evidence to inform their decisions. The systematic reviews provide a high
      quality synthesis of the current literature, saving time for busy people. To make
      the library more user-friendly, the collaboration plans to produce a consumer
      summary for each topic in the Database of Systematic Reviews and a cancer library
      aimed at the general public. In contrast to some of the questionable health
      related resources on the Web, the Cochrane Library is an authoritative reference
      that can help physicians with everyday treatment decisions. The collaboration's
      commitment to keeping its resources up to date through vigorous support of
      reviewers should ensure that it remains a valuable Internet tool for physicians.

PMID- 10932555
TI  - [Stability of therapeutic outcome after child- and adolescent psychoanalytical
      therapy--a five-year catamnesis].
AB  - In the Heidelberg study about psychoanalytic therapy with children and
      adolescents 133 cases have been studied in a naturalistic design. Up to now
      results were published on the basis of assessments of experts only. This follow
      up study has investigated the stability of therapy outcomes from the perspectives
      of different raters. For that outcome has been rated five years after the end of
      treatment by experts, parents and children themselves. Good outcomes have been
      stabile and have shown even after five years. Single variables showed further
      improvement in the time of follow-up, for example the social communicative
      impairment with parents. Thus the high rate of successful longterm psychoanalytic
      therapies with children and adolescents could be confirmed from different rater
      perspectives.

PMID- 10932556
TI  - [Zurich Intervention Planning and Evaluation Form (ZIPEF): a procedure for
      quality control of therapeutic interventions].
AB  - This paper introduces the Zurich Intervention Planning and Evaluation Form
      (ZIPEF). The instrument covers (1) treatment problems, (2) interventions as to
      type, duration, and time expenditure, (3) treatment outcome and (4) causal
      factors. A total of 413 treatment problems were evaluated with the ZIPEF in a
      public child and adolescent psychiatric service. Depending on the target (e.g.
      symptoms, personality, relationship) the distribution of types of intervention
      differed. Time expenditures were significantly higher only for client-centred
      interventions than for parent counseling and similar for all other interventions.
      Treatment outcome and cooperation were independent from type of intervention. The
      main causal factor of treatment outcome for almost all types of interventions was
      cooperation followed by resources in some types of intervention. Complexity of
      the treatment problem tended to be another important determinant for treatment
      outcome. In summary, the ZIPEF can contribute to quality management in the area
      of intervention planning and evaluation of clienteles with mental health
      problems.

PMID- 10932557
TI  - [Pilot study of the relationship between attachment styles and problem perception
      in a sample of 9-11 year old children with behavioral disorders].
AB  - Using the Separation Anxiety Test, this study assessed the attachment patterns in
      a sample of 27 boys and girls in psychotherapeutic treatment to test the
      hypothesis of a relationship between attachment styles and problem perception
      (using the problem questionnaire of Westhoff), and concentration. In conformity
      with the hypothesis, results demonstrate children with anxious-avoidant
      attachment showing less, those with anxious-ambivalent attachment indicating more
      problems than average. There was a general tendency for children with behavioral
      disorders reporting more problems than a comparative sample of 19 school
      children. No correlation was found between attachment styles and concentration
      (assessed via the d2-test). The concentrative abilities were generally reduced in
      the clinical sample. The results are discussed in relation to action-theoretical
      assumptions.

PMID- 10932558
TI  - [Development of psychogenic disorders: an integrative model].
AB  - On the basis of clinical experience and empirically based data an integrative
      model of how psychogenic disorders develop is described in this article. The
      development-psychological steps of maturation from the uterine period to
      adolescence are examined with regard to the respective basic conflict to be
      derived from the step, and the disorder forms neurotization, structural disorder,
      and traumatisation are differentiated. Especially the process character of the
      respective development from the basic conflicts over the different coping
      strategies up to the symptom outbreak is emphasized.

PMID- 10932559
TI  - Health beliefs and optimism as predictors of preventive health decisions in Hong
      Kong Chinese.
AB  - The effects of components of the Health Belief Model and optimism on preventive
      intention were examined in 144 Hong Kong Chinese. Two variables related to the
      Health Belief Model, susceptibility and severity, were experimentally manipulated
      for an imaginary flu outbreak and a hypothetical vaccine. Participants indicated
      their intention to take the hypothetical vaccine after reading each of the 4
      combinations of high versus low susceptibility and severity. Analysis suggested
      that both higher susceptibility and higher severity were associated with stronger
      behavioral intention to take the vaccine. Higher optimism scores were
      significantly associated with lower intention to take preventive action. In
      addition, a significant interaction was observed for optimism and severity. The
      effect of optimism was higher when severity was low than when it was high.
      Implications of these findings for research among Chinese were discussed.

PMID- 10932560
TI  - Retrospective self-reports of changes in homosexual orientation: a consumer
      survey of conversion therapy clients.
AB  - We present the results of a survey of 882 dissatisfied homosexual people whom we
      queried about their beliefs regarding conversion therapy and the possibility of
      change in sexual orientation. There were 70 closed-ended questions on the survey
      and 5 open-ended ones. Of the 882 participants, 726 of them reported that they
      had received conversion therapy from a professional therapist or a pastoral
      counselor. Of the participants 779 or 89.7% viewed themselves as "more homosexual
      than heterosexual," "almost exclusively homosexual," or "exclusively homosexual"
      in their orientation before receiving conversion therapy or making self-help
      efforts to change. After receiving therapy or engaging in self-help, 305 (35.1%)
      of the participants continued to view their orientation in this manner. As a
      group, the participants reported large and statistically significant reductions
      in the frequency of their homosexual thoughts and fantasies that they attributed
      to conversion therapy or self-help. They also reported large improvements in
      their psychological, interpersonal, and spiritual well-being. These responses
      cannot, for several reasons, be generalized beyond the present sample, but the
      attitudes and ideas are useful in developing testable hypotheses for further
      research.

PMID- 10932561
TI  - Comparison of conduct-disordered behavior in crack-dealing versus nondealing
      juvenile offenders.
AB  - Currently, little research has investigated psychosocial functioning among
      juvenile crack dealers, and there appear to be few studies comparing dealers to
      nondealing juvenile offenders. The current study examined whether juvenile crack
      dealers display more severe conduct-disordered behavior than their nondealing
      delinquent peers. The records of 130 adolescent males committed to a residential
      training school were studied. Analyses indicated that crack dealers were younger
      when first arrested, had more arrests and commitments, and met more DSM-III-R
      conduct-disorder criteria than their nondealing delinquent peers. In addition,
      the DSM-III-R conduct-disorder criteria met by dealers were more severe, and
      dealers were more likely to be rearrested within six months following release.
      Overall, significant differences between crack dealers and nondealing juvenile
      offenders were found; dealers displayed a more delinquent history and a more
      serious and violent conduct disorder than their nondealing yet delinquent peers.

PMID- 10932562
TI  - Lost letter returns on five topics from urban waterfront, and smaller rural
      communities.
AB  - Of 850 letters "lost" in Florida, 339 (39.9%) were returned in the mail and
      indicated across 5 addressees, 2 sizes of community, and 2 destinations,
      community size and addressees' affiliations were associated with returned
      responses, but not destinations. These findings seem to indicate that there was
      no bias in the willingness of people to help some strangers with a mailing
      address in another Florida county. The similarities of our findings with other
      measures of public response were discussed.

PMID- 10932563
TI  - Criterion-related validity of the Marital Disaffection Scale as a measure of
      marital estrangement.
AB  - The Marital Disaffection Scale was administered, along with measures of positive
      feelings towards spouse, problem-drinking behavior of spouse, workaholic behavior
      of spouse, and marital status, to 323 female members of the American Counseling
      Association. Scores on the Marital Disaffection Scale showed significant inverse
      correlations (r = -.94) with positive feelings towards spouse and (rpb = -.63)
      with marital status. Scores on the Marital Disaffection Scale showed significant
      positive relationships (r = .36) with spouse's problem drinking behavior and (r =
      .48) with workaholic behavior of spouse. The results support the use of the
      Marital Disaffection Scale as a measure of emotional estrangement in marriage.

PMID- 10932564
TI  - Paranormal belief, experience, and the Keirsey Temperament Sorter.
AB  - 121 college students completed the Anomalous Experience Inventory and the Keirsey
      Temperament Sorter. Multiple regression analyses provided significant models
      predicting both Paranormal Experience and Belief; the main predictors were the
      other subscales of the Anomalous Experience Inventory with the Keirsey variables
      playing only a minor role.

PMID- 10932565
TI  - Sexual satisfaction among married women age 50 and older.
AB  - Correlates of sexual satisfaction were identified in a sample of older married
      women. A 70-item questionnaire was mailed to an age-stratified sample of 5,000
      married persons, including 1,000 married women over the age of 50. Usable
      questionnaires were received from 148 participants (14.8% return rate).
      Hierarchical multiple regression analysis, using sexual satisfaction as the
      dependent variable, yielded five predictor variables that accounted for a
      significant portion of the variation in sexual satisfaction (Cumulative R2 =
      .73). These results serve as a reminder that sexual interactions cannot be
      compartmentalized but must be considered within the context of the overall
      marriage relationship. Given the low return rate, interpretations should be
      limited until replication with an adequate sample has been completed.

PMID- 10932566
TI  - Social adjustment in bipolar and unipolar single-episode and recurrently
      depressed inpatients.
AB  - Social adjustment scores were compared using the Social Adjustment Scale for 24
      inpatients with single-episode major depression, 72 with recurrent major
      depression, and 28 with bipolar disorder. There were no differences between the
      three groups either in overall score or on single scales.

PMID- 10932567
TI  - The 1999 Balkan war: changes in ratings of values and prowar attitudes among
      French students.
AB  - This study investigated the association of Kosovo's 1999 war with a value rating
      of 56 female French students and links between values evaluated at two times
      (before and during the war) and attitudes towards the Balkan war. Subjects
      completed a survey of 15 values by means of a 9-point Likert-type scale one month
      before the beginning of the Balkan war (Time 1) and during the war, 3 mo. later
      (Time 2). Attitude towards the war was also measured by means of a 4-item scale
      completed at Time 2. Analysis indicated two slight unpredicted shifts:
      Universalism and Stimulation value-types were rated higher at Time 2 than at Time
      1. Moreover, two value-types were consistently correlated both at Times 1 and 2
      with prowar attitudes: conformity (r = .29 and .27) and universalism (r = -.29
      and -.43). This latter result, consistent with our hypothesis, suggested that
      individuals' values represent modest but significant correlates of prowar
      attitudes.

PMID- 10932568
TI  - Predictors of support to legalize a state lottery in Alabama counties.
AB  - In Alabama support for a lottery to fund education was correlated with indices of
      low income.

PMID- 10932569
TI  - A test of Monroe's Motivated Sequence for its effects on ratings of message
      organization and attitude change.
AB  - The experiment examined Monroe's Motivated Sequence, an organizational pattern
      commonly taught in basic speech courses for its effects on attitude change and
      ratings of comprehensibility of messages. Treatment groups of 21, 23, and 24
      participants read one of three versions of a persuasive message that advocated a
      $50 fee increase to improve parking facilities on campus. One version represented
      Monroe's five-step sequence, a second version reversed the five steps, and a
      third randomly ordered the steps. A control group of 22 read a message unrelated
      to the parking issue. Analysis showed no differences in attitude change across
      the four groups. The Monroe sequence condition did produce significantly higher
      ratings of comprehensibility on one of four comparisons.

PMID- 10932570
TI  - Psychometric properties of the Rosenberg Self-esteem Scale among people with
      arthritis.
AB  - After 30 years of use the factor structure of the Rosenberg Self-esteem Scale
      remains the subject of debate. Most studies have focused on school-aged or
      undergraduate students. There are few psychometric data for older people or for
      those with disabilities. This study compared the factor structures of the
      Rosenberg Self-esteem Scale among 117 adults with arthritis and 185 undergraduate
      students. A two-factor solution provided the best fit for both samples, although
      the item content of the factors differed slightly. Further investigation is
      required to assess whether the difference is due to age or the presence of
      physical disability. Nonetheless, the scale discriminated well between students
      and adults with arthritis.

PMID- 10932571
TI  - Social character of materialism.
AB  - Scores for 170 undergraduates on Richins and Dawson's Materialism scale were
      correlated with scores on Kassarjian's Social Preference Scale, designed to
      measure individuals' character structure. A correlation of .26 between
      materialism and other-directed social character suggested that an externally
      oriented reference system guides materialists' perceptions, judgments,
      acquisitions, and possessions.

PMID- 10932572
TI  - Effect of exposure to photographs of thin models on self-consciousness in female
      college students.
AB  - The purpose of this study was to assess the immediate influence of brief exposure
      to images taken from print media on the general self-consciousness and body self
      consciousness of 67 college women. After viewing photographs of either thin
      female models or control photographs, the women completed the Self-consciousness
      Scale and the Body Self-consciousness Questionnaire. Although alpha was .45, the
      college women who looked at images of thin female models gave immediate ratings
      significantly (p < .001) higher on both general Self-consciousness and Body Self
      consciousness than those who looked at control images.

PMID- 10932573
TI  - Stability of Tringo's hierarchy of preference toward disability groups: 30 years
      later.
AB  - The hierarchy of preference toward disability groups was measured for 171
      subjects on 16 disabilities. Results indicated that the hierarchy of preference
      reported by Tringo (1970) exists today despite many efforts by society to remove
      such stereotypes. Further, the rank-order of the hierarchy appears to be quite
      stable in that only individuals with cancer show an appreciable change in
      relative position.

PMID- 10932574
TI  - Effect of feedback expectancy on NEO-Five Factor Inventory scores.
AB  - Although Costa and McCrae have indicated that respondents can strategically self
      present on the NEO-Five Factor Inventory when instructed to do so, little
      research has examined the situational factors related to the motivation to self
      present. This study examined feedback expectancy concerning test performance as
      one variable that might have relevance to strategic self-presentation on the NEO
      Five Factor Inventory. Participants (N = 108) completed the inventory under one
      of three feedback expectancy conditions: public feedback, private feedback, or a
      control condition. Multiple analyses of variance indicated no significant
      differences on the inventory's domain scores among conditions, suggesting that
      feedback expectancy was not related to performance.

PMID- 10932575
TI  - Confidence interval formulas for split-half reliability coefficients.
AB  - Confidence interval formulas for the Spearman-Brown and the two-part coefficient
      alpha are presented.

PMID- 10932576
TI  - On the epidemiology of violent juvenile crime in America: a total arrest
      referenced approach.
AB  - The catalyst for this study was a widely publicized U.S. government-sponsored
      report forecasting alarming increases in violent juvenile crime. Working from
      data for the entire United States given in annual FBI Uniform Crime Reports, the
      study presented a descriptive statistical, historical profile of violent juvenile
      crime in America based on the percentage of all arrests for criminal homicide,
      forcible rape, robbery, and aggravated assault attributable to juveniles, 1941
      1995. Markedly different patterns resulted from focusing on rates and rates of
      change calculated for 1-, 5-, and 10-yr. periods. Thus, for example, the most
      recent 5-yr. trend for criminal homicide indicated an average annual increase of
      7.81% in the incidence of arrests attributable to juveniles, with a corresponding
      projected increase of 117% from 1995 to 2010. An average annual rate increase of
      5.13% was indicated over the most recent 10-yr. period, leading to a predicted
      increase of 77% in 2010 as compared to 1995. By sharp contrast, focusing on the
      15.3% rate increase which occurred in the most recent single year led to the
      expectation that juvenile arrests will account for 229% more of this nation's
      criminal homicide arrests in 2015 than was the case in 1995. In every case,
      widely discrepant, 15-yr. projection differences such as those noted above, are
      magnified considerably if we assume validity of U.S. census estimates concerning
      increases in the size of America's juvenile population over the time period
      considered. Results of the study are taken to underscore the importance of
      qualifying archival data-based inferences about violent juvenile crime, in terms
      of the specific measure(s) used and time-frame context(s) of the unit(s) of
      analysis.

PMID- 10932577
TI  - Obsession-compulsion, locus of control, depression, and hopelessness: a construct
      validity of the Arabic Obsessive-Compulsive Scale in American and Kuwaiti
      students.
AB  - In samples of 144 American and 209 Kuwaiti college students, the correlations
      among scores on the Arabic Obsessive-Compulsive Scale and external locus of
      control (.26, .25), depression (.31, .55) and hopelessness (.27, .43) were
      significant and positive in both samples, denoting the construct validity of the
      Obsessive-Compulsive Scale. Thus, it can be recommended for use in both
      countries.

PMID- 10932578
TI  - Research on mental retardation: an agenda for the future.
AB  - This article summarizes the results of a study carried out on 12 scientific
      journals that deal with research on mental retardation. The purpose was to
      analyze the type of research currently being published. Data shows that, although
      most of research on mental retardation from 1991 to June, 1999 agrees with the
      multidimensional system proposed by the AAMR in 1992, research still tends to
      focus on a psychopathological model when considering people with mental
      retardation. We conclude by offering several suggestions on the need for a
      collaborative approach between researchers and professionals and the benefits of
      developing a supportive culture for research.

PMID- 10932579
TI  - Attitudes toward death-related choices.
AB  - In 99 high school students, attitudes toward abortion, capital punishment, and
      suicide were not associated.

PMID- 10932580
TI  - ABC relaxation theory and the factor structure of relaxation states, recalled
      relaxation activities, dispositions, and motivations.
AB  - ABC Relaxation Theory proposes 15 psychological relaxation-related states (R
      States): Sleepiness, Disengagement, Physical Relaxation, Mental Quiet,
      Rested/Refreshed, At Ease/At Peace, Energized, Aware, Joy, Thankfulness and Love,
      Prayerfulness, Childlike Innocence, Awe and Wonder, Mystery, and
      Timeless/Boundless/Infinite. The present study summarizes the results of 13
      separate factor analyses of immediate relaxation-related states, states
      associated with recalled relaxation activities, relaxation dispositions, and
      relaxation motivations on a combined sample of 1,904 individuals (group average
      ages ranged from 28-40 yr.). Four exploratory factor analyses of Smith Relaxation
      Inventories yielded 15 items that most consistently and exclusively load
      (generally at least .70) on six replicated factors. These items included happy,
      joyful, energized, rested, at peace, warm, limp, silent, quiet, dozing, drowsy,
      prayerful, mystery, distant, and indifferent. Subsequent factor analyses
      restricted to these items and specifying six factors were performed on 13
      different data sets. Each yielded the same six-factor solution: Factor 1:
      Centered Positive Affect, Factor 2: Sleepiness, Factor 3: Disengagement, Factor
      4: Physical Relaxation, Factor 5: Mental Quiet, and Factor 6: Spiritual.
      Implications for ABC Relaxation Theory are discussed.

PMID- 10932581
TI  - Some psychometric properties of the Positive and Negative Affect Schedule among
      Australian youth.
AB  - The Positive and Negative Affect Schedule (PANAS) was designed to measure two
      independent or orthogonal dimensions of mood. The present study concerned
      selected psychometric characteristics of the schedule in a convenience sample of
      237 Australian adolescents aged 12 to 18 years. The results were generally
      supportive of the schedule's reported psychometric properties and for its use
      across age and nationality.

PMID- 10932582
TI  - Gender differences in self-image described by Malhotra's Self-concept Scale.
AB  - A survey was made of 69 men and 51 women undergraduate students who described
      their self-image using the 15 adjective pairs of Malhotra's (1981) Self-concept
      Scale. Tests of mean differences showed that the men described themselves as more
      rugged, dominating, unorganized, rational, formal, and colorless; and the women
      described themselves as more delicate, submissive, organized, emotional,
      informal, and colorful. These results are consistent with several descriptions of
      male/female differences in the literature, thereby demonstrating that Malhotra's
      scale may be a simple and convenient way to measure these specific aspects of
      self-image.

PMID- 10932583
TI  - Longitudinal evaluation using the Environmental Deprivation Scale-questionnaire
      with felons.
AB  - The status of 32 felons was examined two years after they had completed the
      Environmental Deprivation Scale. Those who violated parole or probation scored
      significantly differently from those who remained on parole or probation or had
      been released. The questionnaire score could be helpful to identify which felons
      require additional supervision or treatment. Larger samples and extended
      evaluation are necessary for firm conclusions.

PMID- 10932584
TI  - Competitiveness and conflict behavior in simulation of a social dilemma.
AB  - This experiment examined the competitive behavior in a seven-choice Prisoner's
      Dilemma game of 108 adult students (68 women, 40 men) classified as high,
      average, or low in competitiveness based on their scores on the Competitiveness
      Index. Participants were then presented one of three preprogrammed response
      conditions representing (1) Competitive, (2) De-escalating, or (3) Noncompetitive
      conflict behavior from a simulated opponent. Participants high in competitiveness
      engaged in more competitive behavior and reported higher satisfaction with the
      task than those low in competitiveness. As expected, the Competitive conditions
      elicited more competitive behavior than Noncompetitive conditions. The results
      suggest competitive individuals may be particularly susceptible to social cues
      that trigger competitive behavior.

PMID- 10932585
TI  - Response rates to surveys with self-addressed, stamped envelopes versus a self
      addressed label.
AB  - Return rates were studied for a survey on the perceived professional preparation
      of therapeutic recreation specialists by directors of college and university
      recreational therapy programs. Specifically, returns for surveys with self
      addressed, stamped return envelopes enclosed were compared to those with self
      adhering return address labels. Of the 75 surveys sent with a self-addressed,
      stamped return envelope, 42 responses (56%) were returned at a cost of $2.58 per
      respondent. Of the 72 surveys sent with a self-adhering return address label 43
      responses (59.7%) were returned at a cost of $1.56 per response. While there was
      no significant difference in return rates, the self-adhering return address label
      was more cost effective than the self-addressed, stamped, return envelopes.

PMID- 10932586
TI  - African adolescents and their teachers: sex and rural-urban comparisons in
      teachers' perceived behaviors.
AB  - This study investigated rural-urban differences in teachers' perceived behaviors
      among African adolescent boys and girls. On the Perceived Teacher Behavior
      Inventory administered to 354 boys and 530 girls from four rural and urban high
      schools in South Africa no significant sex differences were found on the
      subscales of Generalized Support, Positive Expectations, and Participation. Rural
      boys and girls scored significantly higher, however, than their urban peers on
      the Generalized Support and Participation.

PMID- 10932587
TI  - Reply to Winston and Peters' "On the presentation and interpretation of
      international homicide data...".
AB  - The rationale not previously given for handling a data entry for the USA in a
      prior paper is carefully described, which makes clear the criticism leveled is
      not appropriate. Further, brief murder data were presented to illustrate
      "Brimelow's theory of emotional conditioning," which suggests a strong taboo
      against consideration of any genetic contribution to differences among races.

PMID- 10932588
TI  - Psychosocial predictors of depression among Central American immigrants.
AB  - The present study investigated the relationship between stress and depression
      associated with acculturation among Central American immigrants (64 women, 14
      men) and identified the best predictors of depression among Central American
      immigrants. Elevated acculturative stress was significantly associated with
      higher depression. Family dysfunction, ineffective social support, lack of
      hopefulness toward the future, and low socioeconomic status were also
      significantly associated with high depression. The overall findings suggest that
      Central American immigrants who report high acculturative stress may be "at risk"
      for experiencing depression and that effective family and social support,
      hopefulness toward the future, and socioeconomic status may serve to protect
      against depression during acculturation.

PMID- 10932589
TI  - Smoking acquisition: peer influence and self-selection.
AB  - The study examined and contrasted the extent that peer influence and self
      selection for smoking peers may affect acquisition of smoking by adolescents.
      Data for a U.S. national cohort sample of adolescents (N = 4,444) who were
      nonsmokers in the 1989 Teenage Attitudes and Practices Surveys and were re
      interviewed in 1993 were included. The information included measures of smoking
      behavior and smoking status of both boys' and girls' best friends. Analysis
      demonstrated that, although the effects of both peer influence and self-selection
      of smoking friends occurred, self-selection may play a greater role in
      adolescents' beginning to smoke. This implies that, while teaching adolescents to
      resist peer pressure may be necessary, it is perhaps more important to identify
      factors that influence adolescents' decisions in choosing friends who smoke. This
      could lead to more effective preventive strategies.

PMID- 10932590
TI  - Categorization of videogames: some comments on 'Children and electronic games' by
      Funk, et al.
AB  - Comments are made on an article by Funk, et al. about children and electronic
      games. This author argues the cross-cultural differences and developmental
      effects must be taken into account and that the categorization system of
      videogames based on content is incomplete or too general to cover the complex
      actions of contemporary videogames. These factors alone may have implications for
      research.

PMID- 10932591
TI  - Verification of impression of voice in relation to occupational categories.
AB  - The present study examined how personality traits, physical characteristics, and
      occupational categories derived from listening to human voices are related to
      each other. Stimuli were 25 tape-recorded male vocal samples. In Study 1, 114
      undergraduate and graduate students rated each of the 25 voices on 22 personality
      traits and 11 vocal characteristics. Participants were also given a list of 34
      occupational categories from which they selected one suitable occupational
      category for each of the 25 voices. Of 34 occupations, 20 occupations selected
      most frequently were used in Study 2 wherein 90 junior college students rated the
      voices on the 20 occupational categories. Factor analyses produced three factors
      for personality characteristics, for vocal characteristics, and for occupational
      categories. Also, significant correlations among those factors (both positive and
      negative) indicated participants consistently attributed particular personality
      and vocal characteristics to specific voices and assigned those voices to
      particular occupational categories. Stereotypical perception of voices is
      discussed in terms of earwitness identification.

PMID- 10932592
TI  - Career priority patterns among managerial women: a study of four countries.
AB  - This research examined career priority patterns among samples of managerial and
      professional women in Bulgaria, Canada, Norway, and Singapore. Data were
      collected using questionnaires. Women in all four countries shared similar career
      priority patterns, endorsing patterns that combined both career and family.

PMID- 10932593
TI  - Characteristics of families of soldiers who return prematurely from overseas
      deployments: an assessment from Operation Restore Hope (Somalia).
AB  - Nearly 500 wives, married to enlisted soldiers who deployed to Somalia for
      Operation Restore Hope, participated in a postdeployment study in the summer of
      1993. About 10% of their husbands had returned early from Somalia for family
      reasons. Analysis of their wives' reports suggests that early returns were
      associated most often with childbirth or problematic pregnancies rather than
      other factors such as inexperience with deployments, negative attitudes towards
      the military, a lack of support services, or lower coping abilities. However, in
      hindsight, our results probably reflect compliance with military policy at that
      time for that deployment, under which pregnancy-related concerns were one of the
      most legitimate reasons for permitting an early return. The results support
      sociological theories that highlight the importance of macrosocial factors in
      influencing the lives of individual families somewhat independently of the
      microsocial environment of the families.

PMID- 10932594
TI  - A methodological note on mail survey response rates.
AB  - Five mail surveys of broadcast managers during the 1990s yielded consistently low
      response rates. Implications for research are discussed.

PMID- 10932595
TI  - Factors associated with spouses moving away from their military installation
      during an overseas deployment.
AB  - During overseas deployments, many spouses and families move away from their
      initial military installation, usually to live with or near relatives. Relatively
      little has been known about those who move away even though the issue is of
      importance to the military because its support systems are designed on the
      assumption that family members are living in proximity to those support systems.
      The purpose of this research was to describe the characteristics of those who
      actually moved away during a deployment compared to those who stayed but wanted
      to leave and to those who stayed. Results generally fit a social exchange model
      of reasons for moving, staying, or wanting to move but staying. High stress
      appears to lead to a desire to move but other factors act as barriers or
      facilitators to actually moving. Military family support did not predict moving
      away or staying. Implications for military support services are discussed.

PMID- 10932596
TI  - Neuroendocrine tumors. Introduction.

PMID- 10932598
TI  - Introduction to a revised clinicopathological classification of neuroendocrine
      tumors of the gastroenteropancreatic tract.
AB  - A revised clinicopathological classification of neuroendocrine tumors of the
      gastroenteropancreatic tract has been recently developed under the auspices of
      the World Health Organization (WHO) according to advances in the field of tumor
      biology. Here the classification is briefly outlined and discussed together with
      the guidelines for a correct approach to the histopathological diagnosis of
      neuroendocrine tumors and the interpretation of the classification schemes
      covering clinical (hyperfunctional syndromes included), pathological and
      biological patterns, with special emphasis on tumor prognosis.

PMID- 10932597
TI  - State of the art and future prospects in the management of neuroendocrine tumors.
AB  - Neuroendocrine gastroenteropancreatic tumors are rather rare neoplasms with an
      incidence of 1-2 cases per 100,000 people. They show rather varying tumor biology
      and present sometimes distinct clinical symptoms such as flushing, diarrhoea,
      hypoglycemia and gastric ulcers. The biochemical diagnosis is today significantly
      improved by the introduction of chromogranin A as a general tumor marker, which
      is also useful in histopathology. Today the localization procedures include
      somatostatin receptor scintigraphy as the primary investigation together with CT
      or ultrasonography. The basis for treatment of neuroendocrine GEP tumors is not
      only a curative intent but merely amelioration of clinical symptoms, abrogation
      of tumor growth, maintaining and improvement of quality of life. Surgery has
      always to be considered in the treatment of neuroendocrine GEP tumors. It can be
      performed whenever during the course of the disease but it may be more productive
      in earlier stages. Liver dearterialization procedures can furthermore reduce the
      tumor masses in liver together with laser treatment or radiofrequency therapy.
      The medical treatment includes cytotoxic agents, alpha interferons and
      somatostatin analogues. Somatostatin analogues will always be combined with the
      other two alternatives to reduce clinical symptoms. Chemotherapy is particularly
      useful for patients with more aggressive tumors with high proliferation capacity,
      whereas alpha interferon is beneficial in classical midgut carcinoids with low
      proliferation capacity. Quite recently somatostatin based radioactive tumor
      targeted treatment has evolved with preliminary promising data but further
      studies are needed to deliniate its future role in the treatment of
      neuroendocrine tumors in patients.

PMID- 10932599
TI  - Laboratory tests for neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) often have a good prognosis and have peculiar
      biological characteristics, among which the ability to produce and release
      biologically active substances. Hypersecretion of hormones, biogenic amines or
      growth factors often cause severe syndromes that are very debilitating. Now
      sensitive assays for the measurement of these substances have been developed and
      this has improved the possibility of patient follow-up by means of in vitro
      examinations. The decision about which in vitro examination to be utilised for
      NET management is very difficult because of the NET low incidence, the very large
      number of measurable hormones, the difficulty or low patient compliance for some
      diagnostic tests. In this review we describe the most useful laboratory tests for
      determining the diagnosis of NET, their prognostic significance and the clinical
      value of specific marker evaluation in the follow-up of the NET patient.
      Particular consideration has been given to biomarkers for gastroenteropancreatic
      and sympatho-adrenal system tumours and for prostate and breast cancers with
      neuroendocrine differentiation.

PMID- 10932600
TI  - Results and potential of somatostatin receptor imaging in gastroenteropancreatic
      tract tumours.
AB  - BACKGROUND: Somatostatin receptor imaging with 111In-pentetreotide is widely
      accepted as an essential step in the management of patients affected by
      neuroendocrine tumours of the gastro-entero-pancreatic tract. Many data are
      already available on the high sensitivity of this technique. METHODS: We present
      a review of the published data together with the results of a study involving 253
      patients submitted to somatostatin receptor imaging in three Italian hospitals.
      The patients were divided into two groups treated with different acquisition and
      processing protocols. RESULTS: The overall sensitivity was as high as (169/176)
      96% in both groups, while the specificity was higher in the group in which semi
      quantitative evaluation of somatostatin receptor density was performed: (23/26)
      88% vs (39/51) 76%. The use of this method is recommended to increase the
      specificity of 111In-pentetreotide imaging. CONCLUSIONS: Our results with
      somatostatin receptor imaging in neuroendocrine tumours of the gastro-entero
      pancreatic tract demonstrate that all figures of merit are excellent when imaging
      is accurately performed and analysed by experienced operators.

PMID- 10932602
TI  - Intraoperative use of gamma-detecting probes to localize neuroendocrine tumors.
AB  - Neuroendocrine tumors are characterized by the expression of different peptides
      and biogenic amines. These rare tumors tend to grow slowly and are notoriously
      difficult to localize, at least in the early stages. Surgical removal is the only
      definitive therapeutic option for neuroendocrine tumors and relief from
      hyperfunctional status. The effectiveness of surgical treatment is invariably
      dependent upon the complete surgical excision of all tumor tissue, because
      microscopic and occult disease not readily seen by the surgeon may remain in
      situ, leading to shortened survival. Therefore, pre- and intraoperative
      localization of the primary as well as of metastatic tumors is of utmost
      importance. Radioguided surgery (RGS) is an intraoperative technique that enables
      the surgeon to localize radiolabelled tissue based on the characteristics of the
      various tissues. Concerning gastroenteropancreatic tumors (GEP), intraoperative
      gamma probe examination is able to reveal small tumor sites accumulating (111In
      DTPA-D-Phe1)-pentetreotide more efficiently (> 90%) than somatostatin receptor
      scintigraphy (68%-77%), because lesions with a size smaller than 5 mm in greatest
      dimension could be identified. Furthermore, RGS identified 57% more lesions when
      compared to the "palpating finger" of the surgeon. In medullary thyroid cancer
      (MTC), surgical removal of the tumor is the first and most efficient treatment of
      the disease. Persistent or increasing serum calcitonin and carcinoembryonic
      antigen (CEA) levels imply tumor recurrence after thyroid ablation. For imaging
      recurrent MTC many radiopharmaceuticals have been used to visualize tumor sites,
      but none of them has shown excellent sensitivity. Preoperative somatostatin
      receptor scintigraphy and intraoperative RGS in patients with recurrent MTC
      demonstrate only part of the tumor sites and cannot visualize small tumor sites
      (less than 10 mm). In comparison, RGS using 99mTc(V)-DMSA detects metastases with
      a size of 5 mm in diameter, whereas the "palpating finger" of the surgeon
      localized metastases with a size of more than 1 cm in diameter. In patients with
      recurrent MTC, intraoperative gamma probe examination is able to localize over
      30% more tumor lesions when compared with conventional preoperative imaging
      modalities and surgical findings. MIBG scintigraphy is the most sensitive
      technique for the detection and staging of neuroblastoma (sensitivity 92%;
      specificity nearly 100%). Intraoperative RGS with iodine labelled MIBG has been
      developed to improve the definition of tumor limits or to localize small,
      nonpalpable tumors. Comparison of 123I- and 125I-labelled MIBG revealed a
      sensitivity of 91% and 92%, respectively; the specificity of 125I (85%) was
      significantly higher than that of 123I (55%). In addition to scintigraphy of the
      adrenal glands by precusors of adrenal hormones, imaging with a radiolabelled
      somatostatin analogue is possible; however, (111In-DTPA-D-Phe1)-pentetreotide is
      not specific for any adrenal disease or function and the relatively high
      radioligand accumulation in the kidneys limited the use for detection of tumors
      in the area of the adrenal glands.

PMID- 10932601
TI  - New radiopharmaceuticals for receptor scintigraphy and radionuclide therapy.
AB  - In vitro data have demonstrated a high amount of receptors for various hormones
      and peptides on malignant cells of neuroendocrine origin. Among these, binding
      sites for members of the SST-family (hSSTR1-5) are frequently found, and their
      expression has led to therapeutic and diagnostic attempts to specifically target
      these receptors. Receptor scintigraphy using radiolabeled peptide ligands has
      proven its effectiveness in clinical practice. In addition, initial results have
      indicated a clinical potential for receptor-targeted radiotherapy. Based on
      somatostatin (SST) receptor (R) recognition, the novel radiopharmaceuticals
      111In/90Y-DOTA-lanreotide developed at the University of Vienna as well as
      111In/90Y-DOTA-DPhe1-Tyr3-octreotide (NOVARTIS) both have provided promising data
      for diagnosis and treatment of hSSTR-positive tumors. SSTR scintigraphy using
      111In-DTPA-DPhe1-octreotide has a high positive predictive value for the vast
      majority of neuroendocrine tumors and has gained its place in the diagnostic work
      up as well as follow-up of patients. We have used 111In-DOTA-lanreotide
      scintigraphy in 166 patients since 1997 and have seen positive results in 93% of
      patients. In 42 patients with neuroendocrine tumors comparative data were
      obtained. As opposed to 111In-DTPA-DPhe1-octreotide and 111In-DOTA-DPhe1-Tyr3
      octreotide, discrepancies in the scintigraphic results were seen in about one
      third of patients concerning both the tumor uptake as well as tumor lesion
      detection. Initial results both with 90Y-DOTA-lanreotide as well as 90Y-DOTA
      DPhe1-Tyr3-octreotide has pointed out the clinical potential of radionuclide
      receptor-targeted radiotherapy. This new therapy could offer palliation and
      disease control at a reduced cost. The final peptide therapy strategy is most
      probably cheaper than conventional radiotherapies or prolonged chemotherapies.
      Overall, receptor-mediated radiotherapy with 90Y-DOTA-lanreotide/90Y-DOTA-DPhe1
      Tyr3-octre otide might also be effective in patients refractory to conventional
      strategies.

PMID- 10932603
TI  - Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies.
AB  - Positron emission tomography (PET) performed with various radiolabelled compounds
      facilitates the study of tumor biochemistry. If the tumor uptake of an
      administered tracer is greater than that of surrounding normal tissue, it is also
      possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose
      (FDG) was attempted to visualize the tumors, since this tracer had been
      successfully used in oncology, reflecting increased glucose metabolism in
      cancerous tissue. However, this tracer was not to any significant degree taken up
      by the neuroendocrine tumors. Instead, the serotonin precursor 5
      hydroxytryptophan (5-HTP) labeled with 11C was used and showed an increased
      uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake
      was selective and the resolution so high that we could detect more liver and
      lymph node metastases with PET than with CT or octreotide scintigraphy. One
      problem was, however, the high renal excretion of the tracer producing streaky
      artifacts in the area of interest. Using the decarboxylase inhibitor carbidopa,
      given as peroral premedication, the renal excretion decreased 6-fold and at the
      same time the tumor uptake increased 3-fold, hence improving the visualization of
      the tumors. When patients were followed during treatment with PET using 5-HTP as
      a tracer, a > 95% correlation between changes in urinary 5-hydroxyindoleacetic
      acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was
      observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5
      HIAA is considered to be uncommon in endocrine pancreatic tumors (EPTs).
      Initially, 11C-labeled L-DOPA was attempted as another amine important in the
      APUD system. With L-DOPA about half of the EPTs, mainly functioning tumors, could
      be detected. Recently, 5-HTP was explored as a universal tracer also for EPT and
      foregut carcinoids, extending the PET-examination to both thorax and abdomen
      (whole-body PET-examination). With this method we were able to visualize small
      lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not
      detectable by any other method including octreotide scintigraphy, MRI and CT.
      Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A)
      inhibitor harmine with promising results in non-functioning EPTs. We are
      currently exploring a wide range of biochemical systems, including enzymes and
      receptors, both for neurotransmitters and for peptides and proteins in in vitro
      assays with the potential to use some of the developed tracers for in vivo
      visualization and tumor biological studies. In conclusion, PET is a valuable tool
      in the diagnosis of neuroendocrine tumors. It can detect small lesions in the
      thorax and abdomen not detected by other methods, which has been of great value
      preoperatively in several cases. It detects more lesions in the liver and lymph
      nodes than other methods and furthermore, it can be used to monitor treatment
      effects.

PMID- 10932605
TI  - In situ radiotherapy with 111In-pentetreotide. State of the art and perspectives.
AB  - 111In-pentetreotide (Octreoscan) and other radiolabeled somatostatin analogs are
      useful in the management of well differentiated neuroendocrine malignancies such
      as carcinoid or islet cell neoplasms. These radiopeptides bind to membrane bound
      somatostatin receptors (sst 1-5) which are over-expressed in a wide variety of
      neoplasms, especially those arising from the neuroectoderm. Imaging advances
      allow for the noninvasive determination of the presence of sst receptors by
      combining radioactivity [111Indium with a somatostatin analog, DTPA-D-phe1
      octreotide (pentetreotide)]. Radiolabeled somatostatin analogs bind to membrane
      receptors and internalization of the complex occurs. Auger emitting somatostatin
      analogs offer a novel and significantly less toxic approach to controlling
      neoplastic diseases by delivering targeted radiation specifically to receptor
      bearing cells while sparing receptor negative cells. Responses of 62-69% in 85
      patients with metastatic neuroendocrine tumors treated with high dose (6-19.6
      GBq) 111In-pentetreotide, specifically targeting tumor somatostatin receptors,
      have been reported. Objective responses observed included biochemical and
      radiographic responses with prolonged survival. This article will discuss and
      review the multi-center data available to date, the mechanisms of action of
      radiolabeled somatostatin analogs, dosimetry, clinical response parameters, and
      toxicity.

PMID- 10932604
TI  - Role of 131I-metaiodobenzylguanidine (MIBG) in the treatment of neuroendocrine
      tumours. Experience of the National Cancer Institute of Milan.
AB  - BACKGROUND: 45 patients with neuroendocrine tumours (22 neuroblastomas, 10
      phaeochromocytomas, 3 para-gangliomas, 6 medullary thyroid carcinomas and 4
      carcinoids) underwent 131I-MIBG therapy. METHODS: All patients, with the
      exception of 5 phaeochromocytoma cases with nonoperable disease, had previously
      been treated with conventional therapies. Patients had a previous diagnostic
      scintigraphy with 131I-MIBG (activity 20-44.4 MBq) or with 123I-MIBG (activity 74
      222 MBq). The therapeutic activity for adults ranged from 3.7 to 7.4 GBq of 131I
      MIBG; for children from 2.7 to 5.5 GBq. All treatments were repeated at not less
      than 4-weekly intervals. The neuroblastoma patients were divided into two groups:
      the first included 14 patients with advanced metastatic disease not responding to
      previous treatments; the second included 8 patients with documented residual
      neuroblastoma tissue that could not be surgically removed after first-line
      therapy. RESULTS: In neuroblastoma patients with advanced disease resistant to
      previous therapies 2 out of 14 showed a partial response, 9 stable disease and 3
      progression of cancer. In neuroblastoma patients with residual disease (7
      evaluable out of 8) we obtained 3 partial responses; a stable response was
      observed in 3 patients. The results of MIBG therapy in the group of
      phaeochromocytoma patients (9 evaluable out of 10) consisted of 3 partial
      responses, 5 stable disease and 1 progression. Evaluation of the response carried
      out on the basis of biochemical parameters increased the responses and MIBG
      therapy showed good effectiveness in controlling the functional symptoms. In the
      group of paraganglioma patients we observed 1 complete, 1 partial and 1 stable
      response. In patients with medullary thyroid carcinoma a partial response was
      observed in 1 patient with mediastinal metastases and 2 disease stabilisations
      were seen in another 2 patients. Patients with carcinoids who underwent MIBG
      therapy showed 3 disease stabilisations. The overall toxicity was acceptable,
      especially considering that the majority of our patients had had previous
      myelotoxic treatments (chemotherapy and/or radiotherapy, alone or in
      combination). CONCLUSIONS: On the basis of our experience we can conclude that
      131I-MIBG therapy is effective and also well tolerated.

PMID- 10932606
TI  - New clinical trials for the treatment of neuroendocrine tumors.
AB  - In oncology there is an increasing interest in neuroendocrine tumors, whose
      incidence is generally considered low, although in a recent analysis of 5,468
      cases there was an increase in the proportion of pulmonary and gastric carcinoids
      and a decrease in the appendiceal carcinoids. However carcinoid tumors are
      indolent and their diagnosis is often difficult to carry out, so the true
      incidence may be higher. Surgery remains the treatment of choice and it should
      always be considered in patients with neuroendocrine tumors although a complete
      cure is difficult to obtain. Cytotoxic chemotherapy is the medical treatment for
      highly proliferating neuroendocrine tumors, but it has showed a modest benefit.
      Somatostatin analogues, octreotide and lanreotide are the standard hormonal
      treatment for neuroendocrine tumors. Recently, two trials on lanreotide and
      octreotide have been published, and it is worth noting that in each trial a long
      acting formulation has been used: for lanreotide a prolonged-release formulation
      (PR) which allows an injection of 30 mg every 2 weeks, and for octreotide a long
      acting release formulation (LAR) which allows an injection of 10, 20 or 30 mg
      every 28 days. The results of each trial are very promising. However, there are
      methodological and clinical aspects which make it difficult to carry out new
      trials for studying neuroendocrine tumors. The increasing number of biological
      markers deserve further investigations before their wide use in clinical
      practice.

PMID- 10932607
TI  - Updated recommendations on an established test--ANA.

PMID- 10932608
TI  - Hepatitis A vaccination: should we routinely vaccinate children?

PMID- 10932609
TI  - Doctor, can we talk? Physician-patient communication issues that could jeopardize
      patient trust in the physician.
AB  - The essences of the prostate cancer experience were explored through interviews
      with ten early-stage prostate cancer patients who were approximately one year
      post surgical treatment. One theme that emerged from this modified
      phenomenological study dealt with the relationships patients had with their
      physicians. One of the major concerns expressed by the study participants was a
      lack of communication with their physicians. The study provides evidence that
      physicians and other healthcare providers should work more diligently with
      patient communication in order to provide patients with a full understanding of
      their disease, treatment options, and potential adverse outcomes from treatment.

PMID- 10932610
TI  - Concerning to low molecular weight heparins (LMWHs) in acut coronary syndromes.

PMID- 10932611
TI  - Epidemiology of diphtheria in South Dakota.
AB  - Respiratory diphtheria was one of the most common causes of death among children
      in the pre-vaccine era. Since the introduction of diphtheria toxoid vaccine in
      1920s, and its widespread use by the late 1940s, diphtheria became increasingly
      rare in the United States. However, through the 1970s diphtheria remained endemic
      in some states, with reported incidence rates > 1.0 per million population in six
      states (Alaska, Arizona, Montana, New Mexico, South Dakota, and Washington).
      Starting in 1980, less than five cases have been reported each year in the United
      States. The majority of culture-confirmed cases have been associated with
      importation from other countries. Toxigenic Corynebacterium diphtheriae, the
      organism causing diphtheria, was thought to have become rare or even have
      disappeared from previously endemic areas such as South Dakota. However, during
      four months in 1996, 11 persons (one index case, six patients and four household
      contacts) in an American Indian community in South Dakota were found to be
      infected by C. diphtheriae; six of these isolates were toxigenic. The findings in
      this report indicate that despite 20 years without reported respiratory
      diphtheria cases, toxigenic C. diphtheriae is still present in South Dakota. The
      continuous circulation of toxigenic strains of C. diphtheriae emphasizes the need
      for health care providers throughout South Dakota to promote timely vaccination
      against diphtheria among persons of all ages and ethnic groups, to be aware of
      the clinical signs and symptoms of diphtheria so that cases can be promptly
      diagnosed and treated, and further public health measures can be taken to contain
      this serious disease.

PMID- 10932612
TI  - [Comparison of the number of CAG repeats in the gene for androgen receptors in a
      control Yugoslav population and in patients with schizophrenia].
AB  - INTRODUCTION: Dynamic mutations were recently discovered causing hereditary non
      polyposis colon cancer. Soon almost 15 hereditary neurological diseases were
      described caused by the expansion of trinucleotide repeats in target genes. These
      mutations are unstable: the number of trinucleotide repeats is increasing from
      generation to generation. These mutations do not obey Mendelian low. There is a
      positive correlation between the number of repeats and the severity of clinical
      symptoms, as well as with the age of onset. This fact explains the genetical
      basis of anticipation. Since schizophrenia is showing non-Mendelian way of
      inheritance and anticipation, it is believed that it might be caused by
      trinucleotide repeats in some gene(s). We analysed the number of CAG triplets in
      the gene for androgen receptor (AR) where expansions are causing spinal and
      bulbar muscular atrophy in healthy and schizophrenic subjects. The aim of this
      study was to see if the androgen receptor gene in schizophrenic patients shows
      instability in the number of trinucleotide repeats. PATIENTS AND METHODS: In
      healthy Yugoslav population we analysed 85 X chromosomes from 52 non-related
      individuals (33 females and 19 males) from healthy Yugoslav population and 84 X
      chromosomes (41 females and 2 males) from patients with schizophrenia. DNA was
      isolated from peripheral blood leukocytes and used for further PCR amplification
      of the segment of AR gene containing CAG repeats. The exact number of these
      repeats was determined by electrophoresis on a 5% denaturing polyacrilamide gel
      stained by silver. RESULTS: In healthy Yugoslav population we detected 16
      different AR alleles in which the number of CAG triplets was from 14 to 29. The
      most common alleles were with 23 repeats (14.1%) and with 22 repeats (12.9%). The
      average number of CAG triplets per allele was 20.91. In patients with
      schizophrenia we detected 13 AR different alleles. The number of triplets was
      from 17 to 30. The most common allele was with 22 repeats (25%). The average
      number of CAG triplets per allele was 22.1.

PMID- 10932613
TI  - [Dose-response effect of drugs in the chemotherapy of small-cell bronchial
      carcinoma].
AB  - Dose-intensity is an amount of drug delivered per unit of time, expressed as
      mg/m2/week, regardless of the schedule or route of administration. Relative dose
      intensity is an amount of drug delivered per unit of time relative to an
      arbitrary chosen standard single drug or, in a combination regimen, the decimal
      fraction of the ratio of the average dose-intensity of all drugs of the test
      regimen compared to the standard regimen. Calculations can be made with intended
      (planned) dose intensity or actual or received dose intensity. A positive effect
      of dose intensity on outcome (response rate) has been demonstrated in advanced
      ovarian, colon, breast cancers and lymphomas. Small-cell lung cancer (SCLC) is
      very responsive to chemotherapy, although in the majority of patients
      conventional-dose chemotherapy is not effective in meaningfully prolonging median
      survival. Randomized studies suggest that a dose may be important for the success
      of chemotherapy in SCLC. The aim of the present study was to investigate the
      relation between dose-intensity and tumour objective response in a group of
      patients with SCLC treated with two cysplatin-based regimens. Fifty patients were
      randomized to receive 60 mg/m2 of a cysplatin and 120 mg/m2 of etoposide on days
      1, 3 and 5 (Group A), or the same dose of cysplatin and 120 mg/m2 of epirubicin
      (Group B). The intercylce interval was 4 weeks, and 6 cycles were planned. The
      planned dose-intensity of cysplatin was calculated as 15 mg/m2/wk. However, the
      actual or received dose-intensity of cysplatin was 12.55 +/- 1.7 mg/m2/wk and
      13.62 +/- 3.1 mg/m2/wk in Group A and Group B of patients, respectively. In other
      words, in the combination with etoposide, 83.7% of the planned dose of cysplatin
      has been delivered, while in the combination with epirubicin the cysplatin dose
      intensity was 90.8%. The received dose-intensity of etoposide was calculated as
      77.7% (planned dose intensity was 90 mg/m2/wk and actual dose-intensity 70
      mg/m2/wk). Similarly, the received dose intensity of epirubicin was found to be
      82.3% (30 mg/m2/wk planned and 24.4 mg/m2/wk actual). The average dose intensity
      in Group A was found to be 80.72% and in Group B 86.04%. Compared to patients
      with stable and progressive disease, the patients obtained objective tumour
      response received 5% and 10% higher relative dose intensity of cysplatin in Group
      A and Group B, respectively. Relative dose intensity of etoposide and epirubicin
      were similar in patients with or without objective tumour response. In
      conclusion, a positive relation between cysplatin dose intensity and objective
      tumour response was demonstrated. A higher relative dose intensity of cysplatin
      could be reached in combination with epirubicin compared to combination with
      etoposide.

PMID- 10932614
TI  - [Carcinoembryonic antigen in chronic otitis media with cholesteatoma].
AB  - INTRODUCTION: Carcinoembryonic antigen (CEA) is a cell surface glycoprotein and
      member of immunoglobuline superfamily. Recent studies pointed out that this
      glycoprotein also belonged to the family of intercellular adhesive molecules
      (ICAMs). The presence and increased expression of CEA is noticed in chronic
      inflammation of the skin, gall bladder and extrahepatic biliary tract. According
      to our knowledge, this glycoprotein has not been studied previously in chronic
      inflammations of the middle ear mucosa. The purpose of this study was to
      investigate the presence and distribution of carcinoembryonic antigen (CEA) in
      chronic otitis media with cholesteatoma. MATERIALS AND METHODS: The
      immunohistochemical analysis with high affinity monoclonal antibodies against
      human carcinoembryonic antigen (MEDIX Bochemica AB, Finland) was performed in 71
      mucosal samples with chronic inflammation and in 8 samples of the clinically
      healthy middle ear mucosa. The mucosal specimens were taken intraoperatively from
      different regions of the middle ear cleft during surgery of chronic otitis media
      with cholesteatoma. The control samples were obtained during surgery of traumatic
      perforation of the ear drum. For control staining irrelevant monoclonal
      antibodies were used (Anti-h-PRL clone code 5601: OY Medix Biochemica AB,
      Finland). The complex antibody-CEA antigen was visualized by marked Ig mice
      antibody (HRPO Inep, Zemun) and diaminobenzidine (DAB) as chromogene. After being
      prepared through this specific immunohistochemical analysis, all mucosal
      specimens were analysed under the light microscope. RESULTS: Carcinoembryonic
      antigen (CEA) was not detected in non-inflamed, clinically healthy mucosal
      specimens of the middle ear mucosa. The 71 samptes taken from mastoid, attic,
      promontory and protympanon in chronic otitis media with cholesteatoma showed
      positive staining for CEA expression in 56 (79%) biopsy specimens, while in 15
      (21%) CEA has not been identified. CEA was present in squamous epithelium of
      cholesteatoma, then in fibrous stroma and in endothelial cells of blood vessels
      of the lamina propria in the middle ear mucosa. DISCUSSION: Chronic otitis media
      with cholesteatoma is an invasive disease with aggressive destruction of mucosal
      and bony structures of the middle ear. The pathophysiological mechanism of that
      kind of chronic inflammation has not been clarified. Studies which analysed
      excessive expression of CEA in chronic inflammation of the skin pointed out that
      CEA may induce hyperproliferation of keratinocytes. The findings in our study
      confirmed the high level of expression of CEA in squamous epithelium of the
      middle ear cholesteatoma. The endothelial cells of blood vessels and stroma of
      lamina propria, as well as stroma of the granulation tissue were stained
      positively with labelled CEA antibodies. The results of this study showed that
      CEA was present in chronic inflammation of the middle ear mucosa and in the
      squamous epithelium of cholesteatoma. The precise function of the increased
      expression of CEA in chronic otitis media with cholesteatoma will be the subject
      of our further studies.

PMID- 10932615
TI  - [Vasomotor skin tests in non-eosinophilic and eosinophilic long-term (perennial)
      nonallergic rhinitis].
AB  - INTRODUCTION: It has generally been assumed that "perennial" non-allergic
      rhinitis is a heterogeneous syndrome consisting of at least two groups: non
      eosinopilic and eosinophilic. Opposite to non-eosinophilic group, eosinophilic
      group is characterized by nasal secretion eosinophilia, frequent evolution to
      nasal polyposis or complete ASA triad (nasal polyposis, intrinsic asthma and
      intolerance of non-steroidal anti-inflammatory drugs) and by a good response to
      treatment with anti-histamines and corticosteroids. These characteristics
      obviously separate eosinophilic from non-eosinophilic rhinitis and point out the
      importance of nasal secretion eosinophilia for the evolution and therapy of
      rhinitis. However, the distinction between eosinophilic and non-eosinophilic
      rhinitis can only be made by nasal cytology. Skin tests with vasomotor agents
      were carried out to characterize vasomotor skin reactivity in "perennial" non
      allergic rhinitis and determine whether the patients with non-eosinophilic
      rhinitis differ from patients with eosinophilic rhinitis. METHODS: On the basis
      of the examination of nasal smears of eosinophils, 74 patients with "perennial"
      non-allergic rhinitis were divided into non-eosinophilic (n = 63) and
      eosinophilic group (n = 11). Nasal eosinophilic was considered significant when
      20% and more of the cells in nasal smear were eosinophils. Skin reactivity to
      intracutaneous test with different concentrations of papaverine, metacholine,
      histamine and compound 48/48 was measured, as well as specific skin reactivity to
      control saline solution. Pathological skin reactivity to vasomotor agents was
      defined as hyporeactivity to papaverine (5 mg/mL), when wheal-and-flare skin
      reaction diameter was less than 15 mm; hyper-reactivity to metacholine (0.02, 0.2
      and 2.0 mg/mL), when two of three wheal-and-flare skin reaction diameters were
      greater than 15, 25 and 31 mm, respectively; hyper-reactivity to histamine (0.01,
      0.1, 1.0 and 10.0 micrograms/mL), when three of four wheal-and-flare skin
      reaction diameters were greater than 7, 13, 25 and 40 mm, respectively; and hyper
      reactivity to compound 48/80 (0.01, 0.1, 1.0 and 10.0 micrograms/mL, when three
      of four wheal-and-flare skin reaction diameters were greater than 9, 16, 26 and
      38 mm, respectively. RESULTS: Seventy four patients with "perennial" non-allergic
      rhinitis were included in the study. There were 51 females, age range from 18 to
      57 yrs. (mean 37 yrs.) and 23 males, age range from 18 to 73 yrs. (mean 44 yrs.).
      The difference between the number of females and males was significant (p = 1.1 x
      10(-3)), while no significant difference regarding the age between females and
      males was found (p = 0.122). Significant percentage of eosinophils was found in
      15% of "perennial" non-allergic rhinitis patients, and they were classified into
      eosinophilic group (n = 11). In this group, the percentage of eosinophils varied
      from 20% to 80%, mean 35%. In non-eosinophilic group (n = 63), it ranged from 0%
      to 10%, mean 1%. No significant difference concerning sex and age between the two
      groups of the rhinitis patients was observed (Table 1). There was no significant
      intergroup difference for pathological skin reactivity to papaverine,
      metacholine, histamine, compound 48/80 and saline (Table 2). Total pathological
      skin reactivity to vasomotor agents, single and in combination, was found in 78%
      of non-eosinophilic and in 91% of eosiniophilic rhinitis patients (Table 3). In
      both, non-eosinophilic and eosinophilic groups, frequencies of total pathological
      skin reactivity to vasomotor agents was significantly greater than frequencies of
      total normal skin reactivity (p = 1.1 x 10(-5) and p = 0.007 respectively).
      However, the difference of total pathological skin reactivity to vasomotor agents
      between the two groups was not significant (p = 0.552). (ABSTRACT TRUNCATED)

PMID- 10932616
TI  - [Post-traumatic pulmonary and systemic fat embolism in forensic practice.
      Prospective histological study].
AB  - INTRODUCTION: The more or less subclinical presence of fat emboli in the lungs
      and other vital organs, without ischaemic changes in them, whose presence could
      be postmortem established only by microscopic examination, is termed in forensic
      medicine systemic fat embolism. On the other hand, Fat Embolism Syndrome (FES) is
      a clinical manifestation of the presence and influence of fat emboli in organs,
      with clearly defined neurological, respiratory and cutaneous signs and various
      symptoms, grouped in the so called major and minor signs [8-11]. PURPOSE: The
      purpose of this paper is to establish the frequency of post-traumatic occurrence
      of fat emboli in capillaries of the lungs and other organs in cases where the
      cause of death was not related to pulmonary or systemic fat embolism, but where
      the typical fat depot injury was established. MATERIAL AND METHOD: A prospective
      autopsy histological study was carried out. The sample included 56 cases. The
      clinical and autopsy data were analyzed and compared in order to establish the
      value of injury Severity Score--ISS. Histological samples of all vital organs
      were stained by special technique (Sudan III) and the findings in the lungs and
      kidneys were graded according to Sevitt's criteria [12]. All data were
      statistically analyzed (chi 2 test, ANOVA). RESULTS AND DISCUSSION: The sample
      included 38 males (average age 53.10 years) and 18 females (average age 54.84
      years). The older (ANOVA; p = 0.0017) males (chi 2 = 7.14; p < 0.01), injured as
      pedestrians (ANOVA, p-->0) were statistically significantly more represented. The
      most common determined causes of death were: cerebral contusions (30),
      exsanguination (22), respiratory disorders (9), combustion (6), spinal cord
      contusions (1), and others (complication of injuries, such as inflammations or
      sepsis--4). These causes were singular or competitive plural. The average value
      of ISS was 34.59 (SD = 13.16) and that of outliving period 3.70 days (SD = 5.88).
      The distribution of outliving period was log-normal. Pulmonary fat embolism was
      established in all cases: in 14 cases pulmonary fat embolism of the first degree;
      in 16 of the second grade and in 26 of the third degree. Pulmonary fat embolism
      of the third degree could be the precipitate singular or concurrent cause of
      death. The presence of fat emboli in glomeruli was established in 39 cases: in 30
      cases the kidney fat embolism of the first degree was established, in 6 of the
      second degree and in 3 cases of the third degree. In 11 cases the presence of fat
      globules in brain capillaries was established and in 3 cases in the capillaries
      of other organs (heart, liver, spleen). By analyzing the clinical and autopsy
      data, as well as microscopic findings, we concluded that in four cases the cause
      of death was associated with systemic fat embolism, what previously had been
      missed. CONCLUSION: In all our sample cases pulmonary fat embolism was verified,
      and in a great number of them systemic fat embolism. According to medicolegal
      principles, pulmonary and systemic fat embolism that develop a few hours after
      trauma can be considered as a consequence of typical body fat depot injury. The
      later developed FES could be considered as the complication of such an injury.
      Pulmonary and systemic fat embolism could complicate the basic trauma, e.g.
      craniocerebral, abdominal or thoracic, and could be considered as the
      precipitating cause of death. Because of non-specific and non-characteristic
      macroscopic autopsy findings, pulmonary and systemic fat embolism could be missed
      as the cause of death.

PMID- 10932617
TI  - [Massive pneumonia with severe acute respiratory insufficiency after chicken pox
      in a female patient].
AB  - A female patient who developed massive bilateral pneumonia with severe
      respiratory insufficiency during recovery from varicella, is presented. Blood
      serologic analyses detected the cause of infection--Mycoplasma pneumoniae, while
      Streptococcus pneumoniae was isolated by bacteriological examination of the
      sputum. M. pneumoniae is a causative agent of acute upper and lower respiratory
      airway infections with a frequently mild clinical picture. This agent rarely
      provokes massive pneumonia with severe clinical appearance as described in the
      patient, who had immunodeficiency due to previous infection with Varicella zoster
      virus.

PMID- 10932618
TI  - [Hartnup disease (report of 2 cases in one family)].
AB  - INTRODUCTION: The Hartnup mutation affects the amino acid transport system of the
      intestine and kidney used by a large group of neutral amino acids (monoamino
      monocarboxylic acids) resulting in a characteristic pattern of neutral
      aminoaciduria [2, 5, 6]. METHODS AND PATIENTS: In this research clinical and
      neurological methods and a great number of laboratory tests were used. Patient 1.
      A 16-year-old girl, born in 1972, was a full-term newborn. Her psychomotor
      development was normal. She is the eldest of three children in the family. Till
      the age of 10 the girl was healthy, except for the mild skin disorders on
      uncovered parts of the body, face and hands, occurring in springtime almost every
      year. She had had two exacerbations of the disease. The first exacerbation lasted
      between the end of April and August 22, 1982. The second began in the middle of
      November 1987 and finished on May 31, 1988. A changeable and severe clinical
      feature in this girl was characterized by polymorphic, transient mainly cerebral
      symptoms, papilloedema with peripapillary haemorrhage and pellagra-like skin
      rash. At the beginning of the disease the left spastic haemiplegia with bilateral
      Babinski's reflex and diffuse brain oedema were observed. Signs of the upper
      motor neurone lesion and myoclonic jerks of limbs and face were most persistent
      during the first and second exacerbation of the disease. Dysinhibition
      phenomenon: mandibular, snout and palmomental reflexes were sometimes positive.
      Mental states at the time of hospitalization were changed and characterized by
      bradypsychic, torpid, disoriented in time and confused at the beginning of the
      disease. She had severe psychotic episodes during the second relapse of the
      disease. The symptoms and signs of the disease as well as pellagra-like skin rash
      resolved with nicotinamide therapy. Patient 2. A 38-year-old man; clinically
      healthy, with no skin lesions. A gross aminoaciduria was found in this case.
      However, the amino acids pattern was atypical. DISCUSSION: This new, rare disease
      was described [1] with complex and variable clinical symptoms, intermittent
      course, permanent aminoaciduria and other biochemical features. In our
      symptomatic patient diagnosis of Hartnup disease was established during the
      second exacerbation of the disease. CONCLUSION: Two cases of Hartnup disease, one
      symptomatic and one asymptomatic, were diagnosed in a five member family. A child
      in this family died at the age of 3.5 probably from Hartnup disease.

PMID- 10932619
TI  - [Giant epithelioid leiomyosarcoma of the stomach].
AB  - Epithelioid leiomyosarcoma of the stomach is an uncommon tumour, predominantly in
      old persons. The majority of tumours are small, giant tumours are rare. A tumour
      is more frequent in the upper part of the stomach. It rarely gives secondary
      deposits, almost only large ones. In a few big published series of patients,
      secondary deposit were not found in lymph nodes or other organs. Gastrointestinal
      bleeding, easy fatigue and pain are the usual symptoms of the disease. Endoscopic
      and fine needle biopsy was successful in single cases. A limited wedge gastric
      resection is considered as one of the most appropriate surgical treatments. Major
      resections are reserved for giant tumours infiltrating surrounding organs, and
      for recurrencies. Due to rare involvement of lymph nodes, systematic lymph node
      dissection is not regarded as a necessary procedure. The recurrencies can be
      successfully removed in a number of cases. Chemo- and radiotherapy are generally
      regarded as useless. We present a 61-year old male patient who had discomfort in
      the upper abdomen. CT scan was performed but radiologist missed to diagnose an
      obvious mass in the upper mid-abdomen. Three years later he came with high
      temperature and leukocytosis. The preoperative examination showed conflicting
      results, ultrasonography that the tumour did not belong to the liver but CT scan
      showed that the tumour arose from the left lobe of the liver. Barium swallow
      showed signs of external pressure on the stomach from the right toward left and
      downwards. During the operation, a giant gastric tumour (215 x 139 x 135 mm)
      originating in the antral part of the small gastric curvature was removed with
      distal 2/3 of the stomach. Histologic examination showed epithelioid
      leiomyosarcoma of the stomach with umbilical ulceration. About 50% of the tumour
      was necrotic. There were no lymph node deposits. Temperature and WBC count
      dropped to the normal value soon after surgery. The patient stayed symptom-free
      so far, five months after the operation.

PMID- 10932620
TI  - [Clinical manifestations of familial hypercholesterolemia].
AB  - Familial hypercholesterolaemia (FH) is an autosomal-dominant inherited disorder
      clinically characterized by high serum cholesterol (low-density lipoprotein--LDL
      fraction) concentrations, xanthomas and premature atherosclerosis. Homozygous
      individuals suffer from vascular disease in childhood or young adolescence since
      heterozygous persons are usually at ligh risk of premature cardiovascular death.
      We present a 42-year old female with coronary heart disease and tuber and
      tendinous xanthomas, which appeared as a consequence of delayed diagnosis of
      familial hypercholesterolaemia. She was admitted to the hospital due to unstable
      angina pectoris. On admission the patient was haemodinamically compensated.
      Cardiac rhythm was regular and heart sounds were of normal intensity. She also
      presented two systolic murmurs. The first, the ejection murmur had maximal
      intensity in the second right intercostal space and radiated to the appex. The
      second murmur was regurgitant, generated at the appex and propagated to the
      anterior aixllary line. On inspection, we observed xanthomas in Achillis tendons
      and palmar extensors as well as tuberous xanthomas in the knees and fingers of
      both hands and feet. We also observed bilateral xantholasms. Arcus corneae was
      detected by ophthalmological examination. On admittance, the cholesterol serum
      level was 13.2 mmol/L, and LDL fraction was 7.6 mmol/L. Echocardiography revealed
      sclerosis of the aortic valve and mitral annulus. Coronarography documented the
      three-vessel disease. An aggressive medical treatment, which consisted of bile
      salts and HMGCoA reductase inhibitors, resulted in significant lowering of serum
      cholesterol--more than 30%. However, due to refractory angina pectorts, she had
      to be operated on and aorto-coronary by-pass was performed.

PMID- 10932621
TI  - [T-cell-rich B-cell lymphoma].
AB  - The authors present three patients, one female and two males, with special forms
      of non-Hodgkin's lymphoma, the so called T-cell rich B-cell lymphoma (TCRBCL).
      This is a relatively new entity which has not yet been described in our
      literature. The first diagnosis in our female patient was Hodgkin's disease.
      However, the revision of old and new lymph node samples and use of
      immunohistochemical analysis helped the establishing of diagnosis--TCRBCL. In the
      other two patients the diagnosis of TCRBCL was established on the basis of
      immunohistochemical analysis of the lymph node which indicated the dominating T
      lymphocytes, positive to pan-T antigen (CD45 RO+), with considerably lower count
      of B-lymphocyte elements positive to CD20+. The female patient survived 33 months
      from the time of diagnosis. The other two patients experienced complete remission
      lasting 10 and 12 months after the end of therapy.

PMID- 10932622
TI  - [Helicobacter pylori and coronary disease].

PMID- 10932623
TI  - [Chemotherapy of carcinoma of the germinal epithelium of the testis].

PMID- 10932624
TI  - [Critical approach to the diagnosis of benign prostatic hyperplasia].

PMID- 10932625
TI  - [Importance of knowledge of information on adverse effects and interactions of
      drugs].

PMID- 10932627
TI  - Dr Archer on the right track.

PMID- 10932626
TI  - Concerns still there.

PMID- 10932628
TI  - A lifesaving exam.

PMID- 10932629
TI  - Help your staff help you.

PMID- 10932630
TI  - MedBytes.

PMID- 10932631
TI  - Forum on ethics. The conspiracy of silence.

PMID- 10932632
TI  - It just makes sense.

PMID- 10932633
TI  - See you in court?

PMID- 10932634
TI  - Stress burnout and addiction.

PMID- 10932635
TI  - Prescription for cooperation.

PMID- 10932636
TI  - Publicity helps.

PMID- 10932637
TI  - Reuse of single-use medical devices: informed consent and physician liability.
AB  - This overview addresses the controversial practice of reuse and reprocessing of
      single-use medical devices and the issues this practice raises for physician
      liability. Specifically, we describe the health risks associated with medical
      device reprocessing, analyze the market costs arising from the reuse and
      reprocessing of single-use medical devices, and discuss physician liability for
      failure to obtain informed consent of the patient for the use of reprocessed
      single-use medical devices.

PMID- 10932638
TI  - Abuse of Hispanic elders.
AB  - The nature, extent, and consequences of Hispanic elder abuse are described
      infrequently and often underconsidered. We reviewed information of 16,677
      Hispanic elders living in the community who were abused between 1991 and 1995;
      these were based on valid cases reported to the Adult Protective Services (APS)
      office in Texas. Data did not include nursing home victims. Hispanic elders
      accounted for 20.6% of all elderly cases reported to APS. A 10% to 20% annual
      increase was seen over each of the past 5 years. Self-neglect was the most
      commonly identified form of abuse (63.2%). Cases with more than 1 allegation were
      common. The most common perpetrators (excluding self) were adult children
      (44.6%). Women were twice as likely as men to suffer abuse of any kind.
      Reluctance of victims to become involved in services to ameliorate their
      situations is a major barrier to effective intervention. Strategies to prevent
      abuse of Hispanic elders are needed and should focus on known characteristics of
      the abused and abusers.

PMID- 10932639
TI  - Tarasoff in Texas.
AB  - Texas physicians do not have a statutory duty to warn potential victims of their
      patients' violent conduct but may warn medical or law enforcement authorities if
      the patient is a danger to himself, to the treating physician, or to others.
      Moreover, the Medical Practice Act of Texas does not authorize even permissive
      exceptions to confidentiality, thereby preventing physicians from legally warning
      victims. Nonetheless, 5 Texas appellate courts already have addressed a
      clinician's duty to issue protective warnings to reasonably identifiable victims.
      The approaches of these 5 courts have been similar, but important differences
      warrant attention. In 1998, the Supreme Court of Texas, in a fact-specific
      decision, did not adopt a duty for physicians to protect third persons from their
      patients' violent acts. All Texas physicians should become familiar with the
      emerging jurisprudence of professional protective responsibilities and
      liabilities to third persons who can be harmed physically by their patients'
      violent conduct.

PMID- 10932641
TI  - Coffee debate still percolating.

PMID- 10932642
TI  - New treatment for heart attack.

PMID- 10932643
TI  - Thermoregulation: more than skin deep.

PMID- 10932640
TI  - Tough-love rehab after stroke.

PMID- 10932644
TI  - Less salt for lower blood pressure?

PMID- 10932645
TI  - New nutrition guidelines.

PMID- 10932647
TI  - Celiac disease and stomach upset.

PMID- 10932646
TI  - Herbal hazard.

PMID- 10932648
TI  - White-coat hypertension.

PMID- 10932649
TI  - Islet-cell transplants for type 1 diabetes.

PMID- 10932650
TI  - Choosing a colon cancer screening test.

PMID- 10932651
TI  - Controlling Crohn's disease.

PMID- 10932652
TI  - I'm a 43-year-old woman who recently had a hysterectomy for severe endometriosis.
      Will hormone replacement therapy trigger a recurrence of my disease?

PMID- 10932653
TI  - What are cluster headaches and how are they treated?

PMID- 10932654
TI  - Management of neck lumps--a triage model.
AB  - We report our experience in the out-patient triage of 100 patients presenting
      with a lump in the neck. The out-patient visit consisted of a general history and
      examination, assessment of the upper air and food passages and, where indicated,
      ultrasound and core needle biopsy of the lump. Other investigations were
      performed as appropriate. One hundred neck lump patients were seen in a 9 month
      period. Ninety-six of these lumps were diagnosed on an out-patient basis, only
      four requiring admission for formal excision biopsy. Among the diagnoses were
      eleven lymphomas, nine parotid neoplasms, nine lymph node metastases, five
      thyroglossal cysts, and four branchial cysts. Almost half the patients seen had
      either a reactive lymphadenopathy, or no abnormality. The establishment of a
      tissue diagnosis on an out-patient basis allowed appropriate referrals to be made
      and management plans to be formulated. The theoretical risk of seeding of
      malignant cells in the needle tract is acknowledged and discussed.

PMID- 10932655
TI  - Ultra-conservative skin-sparing 'keyhole' mastectomy and immediate breast and
      areola reconstruction.
AB  - The popularity of skin-sparing mastectomy (SSM) which preserves the breast skin
      envelope is increasing, but the risks and benefits of this approach are only
      beginning to emerge. A technique involving ultra-conservative SSM and immediate
      breast reconstruction (IBR) has been evaluated to establish the surgical and
      oncological sequelae of skin conservation. Between 1994-1998, 67 consecutive
      patients underwent 71 SSM and expander-assisted immediate latissimus dorsi (LD)
      breast reconstructions (follow up, 24.1 months; range, 2-52 months). Breast
      resection, axillary dissection and reconstruction were performed through a 5-6 cm
      circular peri-areolar 'keyhole' incision. Patients were discharged 6.5 days
      (range, 5-15 days) after the 3.9 h (range, 3.0-5.5 h) procedure, and expansion
      was completed by 4.0 months (range, 0-10 months). Local recurrence occurred in 3%
      of breasts at risk, skin envelope necrosis occurred in 10%, and contralateral
      surgery was required to achieve symmetry in 14%. SSM and IBR is an oncologically
      safe, minimal-scar procedure which can be performed by surgeons trained in
      'oncoplastic' techniques. It results in low rates of local recurrence and
      complication, and reduces the need for contralateral surgery.

PMID- 10932656
TI  - Hibernating myocardium in post-ischaemic heart failure: pathophysiology,
      identification and revascularisation.

PMID- 10932657
TI  - Insertion of self-expanding metal stents for malignant dysphagia: assessment of a
      simple endoscopic method.
AB  - AIM: To assess the efficacy, safety and long-term results of self-expanding
      metallic prostheses, placed using an entirely endoscopic method, for the relief
      of dysphagia in oesophageal carcinoma. PATIENTS AND METHODS: A consecutive series
      of 50 patients (30 men, 20 women), aged 43-91 years (median, 75 years) underwent
      stent placement (Ultraflex Stent, Boston Scientific, Watertown, MA, USA) under
      general anaesthesia without fluoroscopic control. RESULTS: Stent placement was
      successful in all patients. Swallowing improved from dysphagia score 4, 3 or 2 to
      score 1 (or 0) in all patients available for long-term follow-up (excluding two
      patients who died, and two who had resection, in the immediate post-stenting
      period). There were two early deaths that were, or could have been, procedure
      related and one early complication, in addition to technical problems in 6 cases,
      all early in the series. Seven patients required endoscopic laser treatment, on
      13 occasions, subsequently for tumour in-growth or over-growth. Of the 46
      patients with long-term stents in situ, 36 patients died with a median survival
      time of 4 months (range 10 days to 24 months). At the time of writing, 10
      patients are still alive with a median survival of 4 months (range 1-11 months).
      CONCLUSIONS: Self-expanding metallic stents provide rapid, safe and effective
      relief of dysphagia. They can provide long-term palliation (> 1 year) with
      endoscopic laser treatment for recurrent in-growing/over-growing tumour.
      Fluoroscopic control is not necessary for the safe and accurate placement of such
      stents.

PMID- 10932658
TI  - Oesophageal syncope.
AB  - Oesophageal syncope is loss of consciousness on swallowing, which is thought to
      be associated with an abnormal vagovagal reflex that leads to transient
      bradycardia. Patients with this potentially lethal condition may present to
      neurologists, cardiologists or gastroenterologists. It may be associated with
      cardio-active drug therapy, previous myocardial infarction, or with an organic
      lesion of the lower oesophagus. Barium and manometric studies, in association
      with ECG monitoring, should, therefore, be carried out in all cases. In many
      patients, however, it appears to be a functional abnormality for which no cause
      can be determined. In the absence of a condition necessitating surgical
      correction, medical therapy in the form of anticholinergic or sympathomimetic
      agents is occasionally helpful. Total denervation of the affected portion of the
      oesophagus has successfully prevented further symptoms, but insertion of a
      programmed cardiac pacemaker is currently the definitive treatment of choice.

PMID- 10932659
TI  - Fissurectomy as a treatment for anal fissures in children.
AB  - INTRODUCTION: Anal fissures, characterised by painful defecation and rectal
      bleeding, are common in both children and infants. A significant proportion are
      resistant to simple laxative therapy, and no simple surgical treatment has been
      described which does not risk compromising sphincteric function. This study
      reports the initial experience of fissurectomy as a treatment of this condition.
      PATIENTS AND METHODS: Over a 36 month period, 37 children with an anal fissure
      were treated by fissurectomy. There were 14 boys and 23 girls, with an age range
      of 17 weeks to 12 years. Fissurectomy was performed under general anaesthetic,
      with additional caudal anaesthesia. Stay sutures were used to avoid the need for
      an anal retractor, thereby preventing stretching of the internal anal sphincter.
      Of the 37 operations, 36 (97%) were performed as day cases and all children were
      discharged on laxative therapy. RESULTS: At review, 6 weeks postoperatively, 30
      (81%) were asymptomatic. Six (16%) patients were symptomatic; however, 4 of these
      had failed to comply with the postoperative laxative regimen. One patient failed
      follow-up. CONCLUSIONS: Fissurectomy is a successful treatment for anal fissures,
      when combined with postoperative laxative therapy. As dilatation of the internal
      anal sphincter is not involved, the risk of iatrogenic faecal incontinence is
      obviated.

PMID- 10932660
TI  - Pancreatic injury: an audit and a practical approach.
AB  - Pancreatic injuries are uncommon, difficult to diagnose and there is no uniform
      standard for treatment. The purpose of this study was to audit the management of
      pancreatic injuries in our practice. Equally important is to attempt to find out
      a simple management plan particularly in the era of increasing conservative
      treatment of injured patients. There were 22 cases of pancreatic injury. The
      average Glasgow coma scale of 10.9 and injury severity score of 29.1. When
      computed tomography is used it has a sensitivity of 33.3% which became 100% if
      repeated or other injuries were identified. There was one case in grade I which
      was treated non-operatively. There were 15 patients in grade II and they were
      treated by drainage. Distal pancreatectomy and splenectomy was the treatment of 3
      patients with grade III injury. One patient had pancreatico-jejunostomy for grade
      IV injury and subsequently developed pancreatic fistula. Pancreaticoduodenectomy
      was the treatment of choice for two patients with grade V and both subsequently
      died. The over all mortality of this series was 22.7% and intra-abdominal
      abscesses noted in 9.1%. This series indicated that there is a need to adopt
      'bail out' procedures particularly in grade IV and V pancreatic injury. A
      simplified management plan is suggested.

PMID- 10932661
TI  - What do trainees think about advanced trauma life support (ATLS)?
AB  - Advanced trauma life support (ATLS) has become a desirable or even essential part
      of training for many surgeons and anaesthetists, but aspects of the ATLS course
      have attracted criticism. In the absence of published data on the views of
      trainees, this study sought their opinions in a structured questionnaire, which
      was completed by trainees in accident and emergency (A & E) (26), anaesthetic
      (82), general surgical (26), orthopaedic (42) and other (5) posts in different
      hospitals (response rate 66%). Of the trainees, 78% had done an ATLS course and,
      of these, 83% considered ATLS a 'major advantage' or 'essential' for practising
      their proposed specialty--100% for A & E, 94% for orthopaedics, 92% for general
      surgery, and 75% for anaesthetics. ATLS was considered a major curriculum vitae
      (CV) advantage by 94%, 85%, 50%, and 45%, respectively. Over 90% had positive
      attitudes towards ATLS, and 74% selected 'genuine improvement of management of
      trauma patients' as the most important reason for doing the course: 93% thought
      ATLS saved lives. Of the respondents, 83% thought that all existing consultants
      dealing with trauma patients should have done the course, and 41% thought it
      offered major advantages to doctors not involved in trauma. Funding problems for
      ATLS courses had been experienced by 14% trainees. This survey has shown that
      most trainees view ATLS positively. They believe that it provides genuine
      practical benefit for patients, and very few regard ATLS primarily as a career
      advantage or mandate.

PMID- 10932662
TI  - Patient outcome alone does not justify the centralisation of vascular services.
AB  - BACKGROUND: The Provision of Vascular Services document from the Vascular
      Surgical Society of Great Britain and Ireland argues for the centralisation of
      vascular services into units served by a minimum of four vascular consultants.
      The rationale for this is the presumed advantages of improved patient care,
      better utilisation of resources and a more comprehensive arrangement of
      consultant vascular cover. Since April 1998, the Royal Surrey County Hospital
      (RSCH) has had a single-handed vascular consultant with out-of-hours cross
      district consultant vascular cover. OBJECTIVES: To use P-POSSUM analysis to
      determine patient outcome from the RSCH vascular unit, and to compare these with
      previously published P-POSSUM analysis from a major vascular unit in Leeds.
      PATIENTS AND METHODS: All patients undergoing major vascular surgery or
      amputation between April and November 1998 were analysed. RESULTS: 86 patients
      underwent 102 surgical procedures in 92 separate admissions. Data retrieval was
      100%. Predicted (E) mortality 16 cases; observed (O) mortality 13 cases; O:E
      ratio 0.80. Predicted morbidity 26 cases; observed morbidity 19; O:E ratio 0.73.
      O:E ratio for mortality from Leeds = 0.83. CONCLUSIONS: Patient outcome in a
      single-handed vascular unit, with cross-district consultant cover, is equivalent
      to that found in a major vascular unit. Centralisation of vascular services
      cannot be justified on the basis of differences in patient outcome.

PMID- 10932663
TI  - The evolution of a vascular surgeon at a district general hospital: is sub
      specialisation inevitable?
AB  - We report a 15-year retrospective audit to evaluate the change in arterial
      surgical commitment on general surgical case mix of a single surgeon with a
      vascular interest at a district general hospital. There was a 409% increase in
      the number of arterial procedures performed combined with a fall of 52% in the
      total number of operations over the study period. We conclude that, with such a
      rapidly growing arterial caseload, sub-specialisation to vascular surgery is
      inevitable.

PMID- 10932664
TI  - Regional variation in varicose vein operations in England 1989-1996.
AB  - AIM: To determine accuracy of Office of Population Censuses and Surveys (OPCS)
      codes for varicose vein (VV) operations and differences in regional activity over
      7 years. METHODS: OPCS codes were obtained for VV operations (L85, L87) for the 8
      English regions 1989/90-1995/96. Data were also obtained for the 4 districts of
      the old Oxford Region. Centrally collected codes for one hospital were compared
      with audit data from the same hospital. RESULTS: There was a marked inter
      regional variation in VV activity, e.g. in 1995/96 the range of
      operations/100,000 population was 102 (Anglia & Oxford) to 138 (West Midlands).
      There was a gradual increase in the number of operations carried out nationally
      from 98/100,000 in 1989/90 to 121/100,000 in 1995/96. The numbers peaked in
      1991/92, coinciding with a 'waiting list initiative'. When compared with audit
      data, accuracy of coding improved throughout the study period. There was a 55%
      inaccuracy in 1989/90 compared with 2% in 1995/96. In each year, codes
      overestimated the volume of work actually carried out. CONCLUSION: OPCS codes
      broadly reflect VV activity. Difference in VV activity in different parts of the
      country are apparent.

PMID- 10932665
TI  - A prospective randomised trial of tourniquet in varicose vein surgery.
AB  - A prospective randomised trial of 50 patients was carried out to assess the
      autoclavable Lofquist cuff (Boazal, Sweden) as a tourniquet in varicose vein
      surgery and determine the effect on bleeding, bruising, cosmesis and patient pain
      and activity. Patients undergoing unilateral long saphenous vein ligation,
      stripping and avulsions were randomised to tourniquet or no tourniquet. Lofquist
      cuffs were applied after inflation to 120 mmHg to the upper thigh for the
      duration of the surgery. Varicose vein grade, duration of surgery, blood loss,
      extent of bruising at 7 days, pain and activity scores over the first week, and
      wound complications and cosmetic result at 6 weeks were recorded. Patients' age,
      sex, and varicose vein grade were similar in the two groups. Peroperative blood
      loss (median, range) was significantly reduced in the tourniquet group (0 ml, 0
      20 ml) compared to the no tourniquet group (125 ml, 20-300; P < 0.01). Operative
      time and thigh bruising (median, range) were also reduced in the tourniquet group
      (30 min, 11-47 min; 72 cm2, 30-429 cm2), respectively, compared to the no
      tourniquet group (37 min, 18-50 min; 179 cm2, 24-669 cm2) both (P < 0.01). There
      was no difference in pain and activity scores in the two groups and cosmetic
      results were also similar. The use of the Lofquist cuff tourniquet during
      varicose vein surgery reduces peroperative blood loss, operative time and
      postoperative bruising without any obvious drawbacks.

PMID- 10932666
TI  - Revision hip arthroplasty activity in a single UK health region: an audit of 1265
      cases.
AB  - Revision hip arthroplasty is an operation which is steadily increasing in number
      and can often be technically challenging. We have utilised a regional hip
      register (the Trent Regional Arthroplasty Study) to analyse the epidemiology of
      revision hip arthroplasties in a single UK health region. The study shows that of
      the large number (1265) of procedures performed over a 7-year period (1991-1997),
      the majority were performed by general orthopaedic surgeons, with 91 different
      surgeons performing the operation and only two surgeons performing more than 20
      procedures per year. Of more than 100 prosthetic combinations used for the
      procedure, the Charnley prosthesis was the most common (38.3% of acetabular
      revisions and 37.5% of femoral revisions). The same component was also the most
      commonly explanted (43%). There was an even geographical spread across the region
      with revision hip arthroplasty being performed in all hospitals with an
      orthopaedic in-patient facility. Prospective audit of this large and varied
      cohort is necessary to determine differences in outcome (if any) between
      'specialist' hip surgeons and general orthopaedic surgeons.

PMID- 10932667
TI  - Tackling osseous hydatidosis using orthopaedic oncology techniques.
AB  - Hydatid disease of bone is rare; success in management is difficult as recurrence
      is common. We report the successful use of orthopaedic oncological techniques and
      technology in treating a patient with hydatid disease affecting his humerus.

PMID- 10932668
TI  - Drain fixation made foolproof.
AB  - A reliable method of securing drain tubing is presented. Knots made from two half
      hitches have been used in the sailing world for many years. They provide a
      strong, slip-free knot which is simple to learn, tie, teach and easy to remove.

PMID- 10932669
TI  - The management of women with breast symptoms referred to secondary care clinics
      in Sheffield: implications for improving local services.

PMID- 10932670
TI  - Database of outcome measures by the Clinical Effectiveness Unit (CEU) of the
      Royal College of Surgeons of England.

PMID- 10932671
TI  - Treatment of infective and potentially infective complications of vascular bypass
      grafting using gentamicin with collagen sponge.

PMID- 10932672
TI  - Colonic diverticular disease.

PMID- 10932673
TI  - The assessment of obesity: methods for measuring body fat and global prevalence
      of obesity.
AB  - Fat is a normal component of the human body that is stored in adipose tissue.
      Obesity can be defined as a condition of excessive fat accumulation to the extent
      that health and well-being are affected. Body fat can be determined in vivo in
      different ways, using rather accurate laboratory techniques or using simple
      estimation techniques that can also be applied in field conditions. For
      population studies, the World Health Organization defines cut-off values for
      obesity based on the body mass index (BMI): weight/height squared (kg/m2).
      Generally, for adults, if the BMI exceeds 25 kg/m2, a subject is considered to be
      overweight, and if the BMI exceeds the value of 30 kg/m2, a subject is considered
      obese. However, the relationship between body fat percentage and BMI differs
      between ethnic groups, and, as a consequence, cut-off points for overweight and
      obesity based on BMI will have to be ethnicity specific. This means that, in some
      populations, the cut-off points could be lower or higher than the recommended
      figures. Adapting cut-off point values will have important consequences for
      prevalence data in some countries as the prevalence of obesity will dramatically
      increase or decrease. The prevalence of obesity, in children as well as in
      adults, is high in many countries all over the world and is rising. Given the
      impact of obesity on health, this is a public health issue that needs to be
      addressed seriously.

PMID- 10932674
TI  - The pathogenesis of obesity.
AB  - Obesity is an extremely challenging medical condition because it is a
      multifactorial disease that lies at the interface between the biology of body
      energy regulation and an environment (physical and sensory) that has been
      increasingly characterized as 'hostile to good health'. The deceptively
      straightforward anthropomorphic definition of obesity is the excessive
      accumulation of body fat. However, obesity is a chronic disease that is much more
      than excessive fat. It involves genetic predisposition and metabolic, hormonal
      and behavioural aspects and results in significant morbidity, reduced quality of
      life, discrimination and early mortality. The development and maintenance of
      obesity can be considered to result from the integration, or the accumulation, of
      small daily errors in energy balance over several months and years. The
      biological factors involved increase the predisposition toward the expansion of
      adipose tissue mass together with the consequences of an environment that
      promotes increased food intake and decreased physical activity. Multiple
      aetiologies may result in similar degrees of obesity.

PMID- 10932675
TI  - Childhood obesity: the genetic-environmental interface.
AB  - Obesity has a high prevalence in children living in industrialized countries.
      Excess adiposity is the result of a prolonged positive energy balance. Both
      genetic and environmental factors are involved. A genetic predisposition to
      obesity has been ascertained from, for example, twin studies. Animal models of
      genetic obesity have been used to identify candidate genes, which have, in some
      cases, also been demonstrated in humans. Genome scanning has highlighted some of
      the human genes that may be involved. Several environmental factors promote an
      imbalance between nutrient intake and nutrient oxidation in genetically
      predisposed children. Fat intake is associated with adiposity in children. The
      low thermogenesis induced by fat intake is another potential contributory factor.
      Oxidative activity in skeletal muscles greatly influences total energy
      expenditure as well as fat oxidation rate. Sedentary behaviour promotes low
      energy requirements in children. Moreover, low skeletal muscle activity reduces
      fat oxidation, favouring fat gain. Several socio-economic and cultural factors
      affect the dietary and physical activity habits of children. Finally, the
      enlargement of the fat mass induces compensatory metabolic reactions to oppose
      further fat gain. Further research on the factors responsible for the
      pathogenesis of obesity is necessary to identify more sensitive targets for the
      effective prevention and treatment of childhood obesity.

PMID- 10932676
TI  - Overweight is risking fate.
AB  - Obesity is the result of ancient evolutionary survival mechanisms in a modern
      environment of affluence. When pressures from this environment generate a long
      term or chronic hypothalamic arousal, neuroendocrine-endocrine and autonomic
      nervous systems are activated, leading to disease-generating 'risk factors'
      including the metabolic syndrome, with visceral fat accumulation as a
      conveniently observable marker. The susceptibility to develop these co
      morbidities is probably dependent on a functional defect of the inhibitory
      feedback control of the hypothalamus-pituitary-adrenal axis by central
      glucocorticoid receptors, often based on a prevalent polymorphism of the gene
      locus for this receptor. This means that moderate ('peripheral') obesity is a
      fairly innocent condition while, when hypothalamic arousal is added, as indicated
      by the internalization of excess body fat ('central' obesity), a highly malignant
      condition develops in genetically susceptible individuals. Obesity research would
      benefit from a distinction between these two types of condition.

PMID- 10932677
TI  - Clinical evaluation of the obese patient.
AB  - An appropriate evaluation is the first step in developing a treatment plan for
      the overweight individual. The medical history should evaluate aetiological
      factors that may have played a role in the development of obesity. The physical
      examination and laboratory tests should extend this evaluation to risk factors
      associated with obesity. The natural history of the development of obesity then
      provides a guide to selecting appropriate treatment algorithms.

PMID- 10932678
TI  - Behavioural treatment of the overweight patient.
AB  - The goal of obesity treatment has changed significantly in the past decade. Where
      once the goal was a reduction to ideal weight, the current objective is the
      achievement of a healthier weight. For many obese individuals, this means losing
      as little as 5-15% of their initial weight. This article briefly describes
      behavioural methods to help obese individuals modify their eating and activity
      habits in order to achieve these new goals. A review of recent studies shows that
      patients treated by a comprehensive group behavioural programme lose
      approximately 9% of their initial weight in 20 weeks and, without further
      treatment, maintain a loss of 5% 1 year later. Methods of improving the
      maintenance of weight loss include increasing physical activity, extending the
      length of behavioural treatment and, with appropriately selected individuals,
      combining behavioural and pharmacological interventions. The importance of
      helping obese individuals adopt realistic treatment expectations is also
      discussed.

PMID- 10932679
TI  - Dietary approaches to reducing body weight.
AB  - Diet is one of the cornerstones of a weight loss programme. Although there is
      little evidence that diet composition plays a clinically important role in the
      absorption or expenditure of energy, it does appear to play a role in food
      intake. Diets with a deficit of 500-1000 kcal per day will produce weight losses
      of between 300 and 1000 g per week, depending on the patient's weight. Formulae
      for estimating energy intake are provided. Starvation diets with an energy intake
      below 200 kcal per day are no longer used, but very low-energy diets with an
      energy intake of between 200 and 800 kcal per day have been used, although there
      is little to support the use of energy levels below 800 kcal per day. Ad libitum
      low-fat diets have been reported to produce weight losses that average 1.6 g per
      day for each 1% reduction in the level of fat. In a meta-analysis, overweight
      subjects lost 5-7 kg before reaching a new plateau. In normal weight subjects,
      the loss was only 0.5 kg. A low-fat diet may be of value in helping patients to
      maintain their weight loss. Higher-protein diets were more effective than low
      protein diets in one clinical trial. The type of carbohydrate in the low-fat diet
      does not appear to influence weight loss. Alcohol, on the other hand, is poorly
      satiating and may replace fat in oxidative processes, thus enhancing the risk of
      obesity.

PMID- 10932680
TI  - Physical activity and obesity.
AB  - The regular practice of physical activity promotes metabolic adaptations that
      facilitate the regulation of energy and fat balance. These effects are important
      for a better control of body weight in the obese individual and should enable him
      or her to involve adipose tissue to a lesser extent in this regulation. Physical
      activity favours a negative energy and fat balance, particularly if activities
      are prolonged and vigorous. The achievement of a negative energy and fat balance
      with physical activity also strongly depends on the nutritional context in which
      it is performed. In the long term, an active lifestyle and low-fat food habits
      are expected to induce a substantial body weight loss in the obese. This weight
      loss is progressively attenuated over time, presumably because of the decreased
      impact of a reduced adipose tissue mass on the regulation of energy and fat
      balance. For the obese individual complying with an activity programme and
      healthy food habits, a body weight loss of 10% is a realistic goal before the
      occurrence of resistance to further loss of body fat.

PMID- 10932681
TI  - Drug treatment of obesity.
AB  - Drugs to treat obesity can be divided into three groups: those which reduce food
      intake, those which alter metabolism and those which increase thermogenesis.
      Monoamines acting on noradrenergic receptors, serotonin receptors, dopamine
      receptors and histamine receptors can reduce food intake. A number of peptides
      also affect food intake. The noradrenergic drugs phentermine, diethylpropion,
      mazindol benzphetamine and phendimetrazine are approved only for short-term use.
      Sibutramine, a norepinephrine-serotonin re-uptake inhibitor, is approved for long
      term use. Orlistat inhibits pancreatic lipase and can block 30% of triglyceride
      hydrolysis in subjects eating a 30% fat diet. The only thermogenic drug
      combination that has been tested is ephedrine and caffeine, but this treatment
      has not been approved by regulating agencies. Leptin is currently in clinical
      trials and other drugs that may modulate peptide-feeding systems are being
      developed.

PMID- 10932683
TI  - The controversy of single-lumen versus double-lumen tube during thoracoscopy.

PMID- 10932682
TI  - Surgical intervention for the severely obese.
AB  - Severe obesity is a grave disease in the U.S. as well as other industrialized
      nations. This disease has many ramifications on both an individual and social
      levels. It affects 12.5 million people in the U.S., according to national survey
      data. The health risks of severe obesity include hypertension, hyperlipidaemia,
      cardiomyopathy, diabetes, hypoventilation disorders, increased risk of
      malignancy, cholelithiasis, degenerative arthritis, infertility, and psychosocial
      impairments. Medical weight reduction programmes have rarely achieved long-term
      success. Most authorities now agree that bariatric surgery is the treatment of
      choice for well-informed and motivated obese patients with acceptable operative
      risks, who strongly desire substantial weight loss or who have severe impairments
      because of their weight. Surgery is indicated for patients with a BMI greater
      than 40 kg/m2, or for those with serious medical co-morbidities and a BMI greater
      than 35 kg/m2. Three procedures, the adjustable silicone gastric banding (ASGB),
      vertical gastric banding (VBG), and gastric bypass (GB), have produced the best
      results to date. Each of these procedures is much more effective than dietary
      therapies. Each has advantages and disadvantages, with GB producing greater
      sustained weight loss in the long-term, with a slightly higher risk of metabolic
      complications. All can be done with surprisingly low operative mortality. The
      pronounced weight loss induced with these operations can relieve and bring co
      morbid diseases, such as diabetes and hypertension, once thought to be only
      barely controllable, into full long-term remission.

PMID- 10932684
TI  - Haemostasis-altering drugs and central neuraxial block.
AB  - PURPOSE: The purpose of this article is to review the literature concerning the
      use of epidural and spinal anaesthesia in patient receiving haemostasis-altering
      drugs, and to provide clear guidelines concerning the safe use of those
      anaesthetic in this category of patients. SOURCE: Relevant articles identified
      via a medline search and recommendation issued from consensus conferences were
      consulted. PRINCIPLE FINDINGS: Bleeding in the spinal canal is a very rare
      occurrence which makes it difficult to conduct randomised studies. Analysis of
      published case reports provide insight concerning the associated risk factors
      that may increase the risk of spinal haematoma. Those risk factors are
      predominantly, anticoagulation and puncture difficulties. Although many studies
      are reassuring, zero events does not mean that the risk is zero. Caution is
      always advised because the consequences of a spinal haematoma are devastating.
      CONCLUSION: Central neuraxial block should be avoided in fully anticoagulated
      patients. In partially anticoagulated patient, strict delays should be respected
      according to the pharmacology of the anticoagulants used, before institution of
      the central neuraxial block. Manipulation of epidural catheters should not be
      done unless the level of anticoagulation is low.

PMID- 10932685
TI  - The 5HT3 receptors and the descending nociceptive pathway--a review.
AB  - There has been a huge and exciting increase in our recent understanding of the
      pathogenesis of pain. Neurophysiological and pharmacological evidence have
      demonstrated that 5-HT now plays an important albeit discrete role in pain
      transmission at various levels of the pain pathway. Although 5-HT is clearly
      involved in spinal analgesia, its mode of action is still obscure and perplexing
      perhaps because it has multiple and often opposing effects mediated by its
      multiple receptor subtypes. The involvement of 5-HT3 antagonists and agonists
      have been found to either facilitate or inhibit nociceptive processing in the
      dorsal horn cells. Thus the understanding of the descending serotonergic
      analgesic system may enable the development of new non-opioid, non-addictive
      analgesics.

PMID- 10932686
TI  - The diaphragmatic compound muscle action potentials (DCMAPs) at different lung
      volumes--a prospective electrophysiological study of the respiratory system.
AB  - Phrenic nerve conduction study and measurements of static lung volumes such as
      functional residual capacity (FRC), total lung capacity (TLC) and residual
      volumes (RV) using body plethysmography were carried out in 31 normal healthy
      male subjects (31 +/- 8 years). The objective was to correlate changes in
      latency, amplitude, duration and area of diaphragmatic compound muscle action
      potential (DCMAPs) with lung volumes and changes in them with changes in
      postures. The mean phrenic nerve latency did not show any significant change with
      lung volumes or postures, but the latency and height of the subject had a
      significant correlationship (r = 0.68). The peak to peak amplitude of DCMAP
      showed a significant relationship with the quantitative lung volumes (r = 0.65).
      The amplitude was significantly higher and duration reduced (p < 0.001) at TLC as
      compared with those at measured FRC and RV in both sitting and supine postures.
      The area under the curve did not change significantly. Similarly, amplitudes and
      latency did not show any significant relation with other anthropometric
      parameters. The study evaluates a new quantitative relationship between DCMAPs
      amplitude and lung volumes. This may be carefully used along with other clinical
      parameters in critically ill patients for an early weaning from ventilator.
      Posture exerts minimal influence on DCMAPs amplitude; since DCMAPs amplitudes
      depends on the position of the diaphragm which in turn depends on dipolic
      potential, its electromagnetic fields and its moving angle subtends at the
      recording electrode, one can confidently use it to predict lung volume in
      respiratory failure due to neuromuscular diseases where subjective lung function
      assessment is impossible. However, a further study is in process in the critical
      care unit to confirm its utility.

PMID- 10932687
TI  - Comparison between two different propofol dosage regimens for insertion of cuffed
      oro-pharyngeal airway.
AB  - Conditions for insertion of the cuffed oropharyngeal airway (COPA) were assessed
      following two different dosage regimens of propofol: group I (n = 40): 1.5 mg.kg
      1; group II (n = 40): 2.5 mg.kg-1. The insertion conditions were evaluated by
      using a scoring system (-, + and +2) of gag and cough reflexes. The necessary use
      of additional dosage of propofol and the duration of post-induction apnea were
      also recorded. There were no significant differences between the two groups in
      the incidence of coughing, gagging and the additional usage of induction agent.
      The mean (+/- SD) duration of apnea was significantly longer in the high dose
      group: 9 +/- 6 min vs 5 +/- 7 min (p = 0.007). Low dose of propofol combines
      efficient insertion conditions with decreased length of post-induction apnea.

PMID- 10932688
TI  - Advance directives: the impact on the anesthesiologist.

PMID- 10932689
TI  - Arteriovenous fistula in chronic renal failure patients: comparison between three
      different anesthetic techniques.
AB  - The creation of arteriovenous fistula is an established form of therapy for
      patients with chronic renal failure. Anesthetic management in such patients is
      governed by the presence of risk factors such as hypertension, ischemic heart
      disease, diabetes, chronic pulmonary disease, anemia, coagulopathy, metabolic
      acidosis and/or hyperkalemia. In an attempt to improve the quality of anesthetic
      care and outcome we designed the present study to compare the different
      anesthetic techniques which are used for creation of arteriovenous fistula.
      Retrospectively we reviewed 164 patients who underwent creation of arteriovenous
      fistula. We retrieved the data concerning the age, sex, ASA class, and coexisting
      diseases. The patients were classified into three groups depending on the
      anesthetic technique received. Group A (n = 48) patients received general
      anesthesia; group B (n = 39), patients received brachial plexus block and group C
      (n = 77), patients received local infiltration anesthesia. Chi-square test was
      used to compare between the percentages among the different groups. The
      percentages of cardiac patients showed significant differences between groups A
      and B and also between groups A and C. There was a significant difference between
      the groups A and B also between the groups A and C but not between groups B and C
      concerning age. ASA classes were not significantly different among the groups.
      Among the total number of patients, 34 were diabetics and 75 patients were
      cardiac. Axillary brachial plexus block was complete in 70% of patients and
      incomplete in 27% and failed in 3% of patients. We conclude that chronic renal
      failure patients are at increased risk during anesthesia. We conclude that
      brachial plexus blockade or local anesthetic infiltration are good alternatives
      to general anesthesia in these patients undergoing creation of arteriovenous
      fistula. Age, ASA class and cardiac status were the three determining factors for
      the choice of the anesthetic technique. Further multivariate prospective study
      are needed to confirm these results.

PMID- 10932690
TI  - Quadriplegia caused by cervical epidural abscess: late diagnosis due to
      iatrogenic sedation and muscular relaxation--case report.

PMID- 10932691
TI  - Transient hemiparesis after lumbar epidural analgesia for labor and delivery--a
      case report.

PMID- 10932692
TI  - Double T-piece, an injector, and Bird ventilator use in MRI suite.
AB  - The double T-piece breathing system is described. The Bird Ventilator Mark 2 is
      utilised as an oxygen pressure jet to drive an injector placed at the distal end
      of the double T-piece breathing system. An active anti-pollution assembly is
      employed. Both the double T-piece breathing system and the anti-pollution
      assembly are valveless. The injector's design is described. The ventilator
      functioned properly at 1.8 m distance from 1.5 tesla electromagnet without
      degrading its imaging. The Bird ventilator, the injector, and the double T-piece
      breathing system are small in size, easy to handle, and can be used for
      paediatric and adult patients.

PMID- 10932693
TI  - [Familial hypercholesterolemia: recognition and prevention of cardiac
      complications at a young age].
AB  - A man aged 35 and a woman aged 30 visited a lipid clinic because of a raised
      total cholesterol level, which was also present in a number of first-degree
      relatives. Apart from the lipid abnormalities they had no risk factors for
      coronary disease. Both proved to have familial hypercholesterolaemia. The man had
      vague angina pectoris symptoms and a high dose of cholesterol synthesis
      inhibitors was prescribed. Coronary angiography showed severe stenoses; a
      coronary balloon angioplasty was successfully performed. The woman, however, died
      at age 33 suddenly from myocardial infarction. Familial hypercholesterolaemia may
      cause unexpected cardiovascular complications and sudden death of young persons.
      Timely diagnosis of the condition on the basis of adequate anamnesis and thorough
      physical examination, more rapid administration of cholesterol-lowering agents
      and alertness for anginous complaints may prevent myocardial infarctions and save
      lives in these patients.

PMID- 10932694
TI  - ["Critical-illness" polyneuropathy and -myopathy].
AB  - Critical-illness polyneuropathy and myopathy (CIPNM) can be considered a part of
      the syndrome of multiple organ dysfunction. CIPNM is the commonest cause of
      muscle weakness acquired in the intensive care unit. Its incidence is 35-80%
      during prolonged mechanical ventilation. For a (differential) diagnosis,
      electrophysiological investigations are usually necessary, and sometimes a muscle
      biopsy. CIPNM may be induced by triggering of the immune response leading to
      increased vascular permeability with tissue invasion of inflammatory cells and
      local damage. There is a relation between myopathy and medication, notably
      corticosteroids. Clinical improvement usually follows when the CIPNM patient
      survives the underlying disease, but weaning from artificial ventilation is often
      difficult, and rehabilitation prolonged.

PMID- 10932695
TI  - [Immunology in medical practice. XXX. Organ transplantation: indications and
      results].
AB  - During the past 30 years, solid organ transplantation has developed into a
      routine medical procedure. Currently, one-year transplant survival rates for
      kidney, heart, liver and pancreas are between 80 and 90%; for most organs, the
      long-term results are fair with 5-year survival rates of 60%. Inclusion criteria
      for potential recipients have become less stringent. These days, potential
      recipients are rarely excluded on the basis of their calendar age alone. The
      development of more and stronger immunosuppressive drugs has facilitated
      transplantation across wider immunological differences between donor and
      recipient with good results. While the number of patients on the waiting lists
      for organ transplantation increased, the number of organs offered for donation
      decreased. This has resulted in waiting times of several years for most organ
      transplantations. While the short-term outcome has improved significantly over
      the past decades, the long-term outcome has not. Most renal transplants, for
      example, are lost due to chronic rejection. The challenge for the future will be
      to improve the long-term outcome of organ transplantation and to decrease the
      morbidity associated with chronic immunosuppressive therapy.

PMID- 10932696
TI  - [Higher prevalence of familial hypercholesterolemia than expected in adult
      patients of four family practices in Netherlands].
AB  - OBJECTIVE: To determine the prevalence of familial hypercholesterolaemia (FH).
      DESIGN: Patient record screening, questionnaire and if necessary, case finding.
      METHODS: Over the period mid-1990-mid-1992 (approximately 2.5 years) 8,800 adult
      individuals (age 18 years and over) in 4 general practices in Hoofddorp, the
      Netherlands, were screened for risk factors for coronary artery disease and
      invited for further analysis. Of the 3,289 selected and invited individuals 2,719
      (83%) were investigated. Total cholesterol concentrations were investigated 3
      times and if the mean value was above 8.0 mmol/l patients were referred to a
      lipid clinic to investigate the possible existence of FH. RESULTS: 114 patients
      were eligible for referral to a lipid clinic of whom 92 (81%) were indeed
      referred. Of these, 38 patients were diagnosed with FH: 23 men and 15 women, with
      a mean age of 47.7 years (range: 21-74). CONCLUSION: The prevalence of FH in this
      investigated population was at least 1:232. This is more than 1:500, the
      estimated number of FH patients in the Dutch population.

PMID- 10932697
TI  - [Hemodynamic and ventilatory complications of mechanical ventilation with high
      intrinsic positive end-expiratory pressure].
AB  - In three mechanically ventilated patients ventilatory and circulatory
      complications resulted from high levels of intrinsic positive end-expiratory
      pressure (PEEPi): progressive pulmonary hyperinflation due to impairment of the
      expiration. PEEPi was initially not considered as the cause of shock and low
      tidal volumes and/or high inflation pressures. In a 74-year-old man the
      circulation deteriorated further when hand bagging was started in an attempt to
      improve his ventilatory condition; after reduction of the respiration rate, he
      recovered well. In a 40-year-old woman with relapsing polychondritis sedation
      helped to reduce the respiratory rate so as to restore sufficient expiratory
      time. A 59-year-old woman developed acute exacerbation of severe chronic
      obstructive pulmonary disease, and went into shock during interhospital ambulance
      transport; she was stabilized after recognition of PEEPi and adjustment of the
      setting of the ventilator. Detection of PEEPi (e.g. by the finding of a deep
      inflation level on physical examination) is more important than exact measurement
      of PEEPi. If PEEPi is detected, the ventilator should be set at PEEP at 80-90% of
      PEEPi, low frequency (e.g. 8/min) and a long expiratory time, and high
      inspiratory flow.

PMID- 10932698
TI  - [Fewer X-rays, while maintaining quality of care using clinical protocols for
      physical diagnosis of ankle injuries].

PMID- 10932699
TI  - [Fewer X-rays, while maintaining quality of care using clinical protocols for
      physical diagnosis of ankle injuries].

PMID- 10932700
TI  - [Fewer X-rays, while maintaining quality of care using clinical protocols for
      physical diagnosis of ankle injuries].

PMID- 10932701
TI  - [Fewer X-rays, while maintaining quality of care using clinical protocols for
      physical diagnosis of ankle injuries].

PMID- 10932702
TI  - [Beneficial effects of vitamin A in measles].

PMID- 10932703
TI  - [Serum lactate level as an indicator of tissue hypoxia in severely ill patients].

PMID- 10932704
TI  - [Insufficient scientific evidence for efficacy of widely used electrotherapy,
      laser therapy and ultrasound treatment in physiotherapy].

PMID- 10932705
TI  - [Fifty years of plastic surgery in Netherlands. VIII. Craniofacial surgery].

PMID- 10932706
TI  - [Diabetes mellitus after treatment with clozapine].

PMID- 10932707
TI  - Comparison of five methods for the detection of measles specific immunoglobulin G
      antibody.
AB  - In this work we compare the sensitivity, specificity and predictive values of
      hemagglutination inhibition (HI), immunofluorescent assay (IFA), biotin
      streptavidin immunofluorescent assay (B/SA-IFA), enzyme-linked immunosorbent
      assay (EIA) and plaque neutralization test (PN). This study includes serum
      samples from children taken before and after vaccination, children with
      clinically diagnosed measles and household contacts. EIA were the most specific
      and better serological diagnostic test. HI and IFA had high sensitivity but low
      specificity. An alternative to EIA is B/SAIFA, which is cheaper than EIA and can
      be used in the study of small outbreaks or in isolated cases.

PMID- 10932708
TI  - Pathogenicity bioassays of Hirsutella thompsonii fisher and H. nodulosa petch
      strains facing up to Tetranychus urticae Koch.
AB  - The objective of this work was to determine, trough bioassays, the most virulent
      strains of Hirsutella to be used as a control alternative in a pest intregrated
      wield program are those which are most pathogenic to CL50 just as H. nodulosa
      (HnC83) with 5 x 10(5) conidia/ml, and H. thompsonii (HtMOR and HtM5) with 1 x
      10(6) and 1.1 x 10(6) conidia/ml respectively. The strain we recommend to attack
      Tetranychus urticae is H. thompsonii HtMOR. Although it did not seem to be the
      most aggressive to CL50, it was the strain that required the lowest concentration
      (0.0014%/1.5 x 10(10)) to kill 95% of the population evaluated. At the same time,
      the strain that we considered as having a lower virulence was HtM2 (4 x 10(6)
      c/ml) and the lowest virulence was detected both in HtC59 and HtC77 (1 x 10(10)
      c/ml).

PMID- 10932709
TI  - Antibiotic 26-deoxylaidlomycin isolated from Streptomyces sp. Ar386 from
      Brazilian soil.
AB  - An actinomycete strain (Ar386) was isolated from the soil of the Araraquara
      region, SP, Brazil. The strain, named Streptomyces jacareensis, formed irregular
      rayed, rugose, grayish-white mycelium with sinuous, branched hyphae carrying rare
      isolated spores; assimilated glucose, galactose, inositol, ribose, maltose,
      sucrose, melibiose and starch but not mannitol, rhamnose, arabinose, xylose,
      lactose and raffinose; and contained LL-diaminopimelic acid in its cell wall. An
      antibiotic active against Gram-positive bacteria, which was characterized as
      being 26-deoxylaidlomycin and which may have application against poultry
      coccidiosis, was isolated from cultures of the strain. This was the first
      isolation of this antibiotic from a microorganism of the genus Streptomyces and
      also the first isolation of this antibiotic in Brazil.

PMID- 10932710
TI  - [Emergent diseases caused by viruses].
AB  - In this work a review on viral emerging infectious diseases is discussed. Some
      examples such as hemorrhagic fevers diseases, the Acquired Immunodeficiency
      Syndrome (AIDS) and zoonotic diseases, are included. In this review are discussed
      the main factors influencing the widespread and geographic distribution of viral
      emerging diseases, finally some important actions directed to strength the
      prevention and control measures of viral emerging diseases, are discussed.

PMID- 10932711
TI  - [Non-specific resistance in Brucella infection].
AB  - Brucellosis is still a critical public health problem in many countries around
      the world. In humans, the infection is mainly acquired through the ingestion of
      milk-derived products from infected cattle. After the penetration of the bacteria
      in the body, several serum components are activated, and the immediate
      consequence is the attraction of phagocytic cells. The evolution of the disease
      often courses to a long lasting form, with frequent relapses. This appears to be
      due to the capability of Brucella's of surviving and, even more, multiplying
      within the mononuclear phagocytic cells. First, the intracellular location
      protects the bacteria from the effect of antibiotics. On the other hand, several
      studies have shown alterations in the phagocytic function. In some cases, the
      defects in phagocytosis are intrinsic to the host. However, Brucella organisms
      also display many mechanisms to evade the intracellular killing, which appears to
      be the reason for the success of the bacterium in dwelling within macrophages.

PMID- 10932713
TI  - Inhibition of trypomastigotes' infectivity by a monoclonal antibody directed to a
      glycoconjugated fraction of epimastigotes of Trypanosoma cruzi.
AB  - In this work it was shown that the infectivity of trypomastigote forms of
      Trypanosoma cruzi was affected upon the interaction with the Monoclonal Antibody
      (McAb) 2E9, which was raised against a glycoconjugated fraction of membranes of
      epimastigotes (Tulahuen strain). Characterization of the epitope recognized by
      this McAb, as well as its effects on complement mediated lysis and host cell
      invasion are reported. Immunocytochemical analysis showed that the McAb was
      reactive with two macromolecules (41-58 kDa) present on Trypanosoma cruzi
      epimastigotes (Tulahuen and Y strain), while it recognized several
      trypomastigotes macromolecules, showing a more intense reactivity with a band of
      80 kDa. By indirect immunofluorescence, it was found there were subpopulations of
      blood and tissue culture derived trypomastigotes which attach the antibody to
      varying degrees. Studies using chemical or enzymatically treated antigens
      suggested that the McAb 2E9 was directed against carbohydrate epitopes, which
      were identified as being--galactosyl residues. In addition, preliminary results
      are shown, suggesting that the epitope recognized by the McAb 2E9 is involved in
      adhesion/or internalization of trypomastigotes.

PMID- 10932712
TI  - [Helicobacter pylori, 13 years after the original publication].
AB  - Helicobacter pylori a gram negative bacilli is related with development of
      gastroduodenal disease as chronic active gastritis, peptic ulcer disease MALT
      type lymphomas and gastric cancer. The WHO defined H. pylori as a human
      carcinogen agent. Helicobacter colonizes the gastric epithelium and promotes
      inflammation and mucosal damage. Third part of the world's population is infected
      by the bacteria and many researchers consider that the mode of transmission
      between human being is via the fecal-oral and/or oral-oral manner. H. pylori may
      be identified in saliva, gastric juice, gastric biopsies and feces by different
      methods. The eradication of this microorganism disminished the gastrointestinal
      tract disease.

PMID- 10932715
TI  - Prevention of nonspecific reactions on reversed passive latex agglutination assay
      (RPLA) for detecting low amounts of staphylococcal enterotoxins.
AB  - The SET-RPLA, from Denka Seiken Co. Ltd., Tokio, a commercial reversed passive
      latex agglutination test kit, has been recommended to establish the
      enterotoxicity capacity of some staphylococcal strains, implicated in food
      poisoning outbreaks that produce low levels of enterotoxins (SE). Despite the
      RPLA specificity, the occurrence of nonspecific reactions when testing low-SE
      producing is common. In order to control these nonspecific reactions the addition
      of purified normal rabbit IgG purified was applied on approximately 350
      staphylococcal isolates from human milk and anatomic sites of healthy dental
      student carriers. The results indicated that addition of 5% (v/v) of purified
      normal rabbit IgG (0.74 mg/mL) to the culture supernatant fluid is a simple and
      reliable tool for the controlling of nonspecific reactions in the RPLA assay.

PMID- 10932714
TI  - Electron microscopy and biological properties of pBR322 DNA condensed with the
      trivalent cations spermidine and hexammine cobalt (III).
AB  - Electron microscopy and the biological properties of susceptibility to DNase I,
      genetic transcription, and transformation of pBR322 DNA compacted with spermidine
      or hexammine cobalt (III), were analyzed in order to characterize the association
      of DNA in its compacted form with these two different trivalent cations.
      Spermidine and hexammine cobalt (III) produced an average 4-fold reduction of the
      DNA perimeter in compact DNA forms, which were doughnut-shaped toroids and
      cylinders. Both compacted DNAs were resistant to the hydrolytic activity of DNase
      I. However, spermidine-condensed pBR322 DNA was 10-fold and 4 to 6-fold more
      active in transcription and transformation, respectively, than naked pBR322. I.
      Hexammine cobalt (III)-condensed pBR322 was inactive in both biological
      properties. An inhibitory effect of hexammine cobalt (III) on RNA polymerase and
      genetic transformation activities was discarded because at higher ionic strength,
      in which DNA is not compacted by hexammine cobalt (III), transcription and
      transformation were similar to those observed with naked DNA. This information
      showed that the interaction of hexammine cobalt (III) with the DNA converted the
      pBR322 DNA into an inert molecule. In contrast, pBR322 did not loose its
      biological properties after its interaction with the polyamine spermidine; i.e.,
      experimental condensation of pBR322 DNA by spermidine produced compacted DNA that
      is more similar to compact native genomes than relaxed DNA. These experiments led
      us to conclude that spermidine-condensed DNA can be used to study the roll of the
      native supercoiling of DNA in the regulation of genetic replication and
      transcription, as well as to study the mechanisms that allow the accessibility of
      the supercoiled or condensed DNA substrate for enzymes.

PMID- 10932716
TI  - Purification and partial characterization of a chromate reductase from Bacillus.
AB  - A soluble NADH-dependent enzyme capable of reducing hexavalent chromium [Cr(VI)]
      to the trivalent form [Cr(III)] was purified from chromate-resistant Bacillus QC1
      2. An enriched single protein band of 24 kDa was observed by SDS-PAGE following
      HPLC ion-exchange and size-exclusion procedures. In the latter step, the chromate
      reductase showed a molecular mass of 44 kDa, which suggested that the enzyme
      consists of two subunits of about 24 kDa. Purified chromate reductase displayed
      optimal activity at a temperature and pH of 37 degrees C and 7.0, respectively.
      The enzyme showed a Km of 0.35 mM for chromate and a Vmax of 50 nmol Cr(VI)
      reduced per minute per mg protein.

PMID- 10932717
TI  - Lectin activity from the cattle tick (Boophilus microplus) saliva.
AB  - The capability of Boophilus microplus saliva (BmS) and lectins to induce
      immunosuppression in mice and to agglutinate erythrocytes from distinct animal
      species were compared. CD-1 mice were distributed into groups (two for each
      substance) of 4-5 animals/group and treated intraperitoneally (i.p.) with 50 mg
      and 150 mg of BmS; concanavalin A (Con A); potato's lectin (PL), striped bean
      lectin (SBL) or 0.1 ml of phosphate buffered saline (PBS). All mice were
      immunized i.p. with 2 x 108 sheep erythrocytes (SE) 48 hours after treatment.
      Five days after immunization sera was obtained from mice to determine anti-SE
      antibody titer by direct hemagglutination. The mean antibody titers (Log2)
      obtained was 5.5 and 4.2 for BmS, 4.4 and 0 for Con A, 5.2 and 4.8 for PL, 4.6
      and 0 for SBL and 7.4 for PBS. BmS and lectins were tested to agglutinate mouse
      (M), rat (Rt), rabbit (Rb), sheep (S) and human A (HA), human B (HB) and human O
      (HO) erythrocytes. BmS agglutinated Rb, S, HA, HB and HO erythrocytes at titer
      (Log2) of 1, 1, 6, 1 and 2 respectively. Con A and PL agglutinated erythrocytes
      from all species tested, while SBL agglutinated M, S and HA erythrocytes. A 50%
      inhibition of agglutination of HA erythrocytes by BmS was observed when D(+)
      Galactosamine and D(+) Glucosamine, at 0.2 M, were used. The results obtained
      indicate that BmS contains a weak nonspecific lectin which is inhibited by
      aminated sugars, and that induces immunosuppression in mice as other lectins.

PMID- 10932718
TI  - beta-Galactosidase production by Kluyveromyces marxianus cultured in shake
      flasks.
AB  - beta-Galactosidase production by K. marxianus was studied in shake flasks. Enzyme
      production was strongly influenced by culture conditions determining oxygen
      transfer rates. Working volume turned out to be the most significant parameter
      affecting enzyme yields: the higher the volume, the higher the specific activity
      of the enzyme. The use of dehydrated whey (as the source of lactose) resulted in
      a large increase in the specific enzyme activity as compared with the use of pure
      lactose. This effect is likely due to a lower dissolved oxygen concentration
      along the fermentation. In the range of kL a between 40 and 90 h-1, enzyme
      activity did not seem to depend on kL a, whereas a drastic drop in the final
      specific enzyme activity was observed for kL a values above 90 h-1.

PMID- 10932719
TI  - Isolation of Vibrio and Pseudomonas from brown shrimp (Penaeus californiensis
      Holmes) intestine.
AB  - Bacteria of the genera Vibrio, Pseudomonas and Aeromonas were isolated from the
      intestine of apparently healthy brown shrimp (Penaeus californiensis Holmes)
      cultured in a tidal pond. Species from these genera of bacteria have been
      reported as shrimp pathogens and have been involved in human gastrointestinal
      disorders related to seafood consumption. Isolation was done first in Marine
      broth, then in selective media (TCBS, Cetrimide and MacConkey). The oxidase
      negative strains were discarded as insignificant to shrimp culture. The
      identification of oxidase positive strains was based in morphological and
      colonial characteristics, biochemical capabilities, and both salinity and
      temperature tolerance. API 20E system and fatty acid analysis were also included.
      Three potentially pathogenic bacteria, Vibrio parahaemolyticus, Vibrio furnissii
      and Pseudomonas putida were isolated and identified from healthy shrimp
      intestine.

PMID- 10932720
TI  - Isolation of Chlamydia psittaci involved in abortion of goats in Mexico: first
      report.
AB  - A group of 35 healthy adult goats ranging from two to six years old were bought
      from a chlamydiosis and brucellosis-free flock; they were vaccinated against
      Brucella melitensis with Rev1 vaccine at reduced doses, and one month later
      placed in isolation units. The animals were one month pregnant at the moment of
      purchase, and during the third month of pregnancy 10 out of the 35 dams aborted.
      Necropsy of the aborted fetus and examination of the foetal membranes was
      performed where no macroscopic lesions were observed. Abomasal liquid, foetal
      lung and liver, and placenta samples were taken for bacteriological analysis
      while sera from the goats that aborted was collected for serological
      investigation. Chlamydia psittaci was isolated in all cases, while no Brucella
      was detected. All sera reacted positive to anti-Chlamydia antibodies by the
      indirect immunofluorescence test. This represents the first report of Chlamydia
      psittaci isolation from cases of goat abortion in Mexico.

PMID- 10932721
TI  - Sensitivity and specificity of an ELISA as a screening test for the diagnosis of
      Brucella ovis in sheep.
AB  - A hot saline extract of Brucella ovis strain REO 198 at a concentration of 5
      micrograms/ml in phosphate buffer pH 7.2 was used to adsorb onto Maxisorb plates
      and incubated at 37 degrees C during 12 h; unadsorbed excess antigen was washed
      off thrice with phosphate buffer containing 0.5% Tween 20. As blocking agent 1%
      skim milk was used. The conjugate used was protein G bound to peroxidase diluted
      1:100. Thirty three sheep sera from bacteriologically confirmed infected animals
      and 39 sheep sera from healthy animals from disease-free zones were used. Sera
      were diluted 1:200. ELISA's sensitivity was 97% and specificity 84%. The cut-off
      value was chosen for a high sensitivity (100%) despite some loss of specificity
      in order to diminish false negative results rendering thus a suitable screening
      test for sheep epididimitis caused by Brucella ovis.

PMID- 10932722
TI  - Molecular cloning of the gene that codes for the pyruvate kinase of Bacillus
      subtilis: primary characterization of a strain carrying this gene insertionally
      inactivated.
AB  - We have cloned and characterized the pykA gene from Bacillus subtilis which codes
      for a pyruvate kinase (PK) enzyme. This gene has been located downstream a
      putative phosphofructokinase gene, suggesting that they are part of the same
      operon. The deduced amino acid sequence of this PK showed a strong similarity to
      other PKs from different sources; however, as it has been found in other bacilli,
      the B. subtilis pykA enzyme had an extra C-terminal sequence consisting of about
      112 amino acid residues. This gene was insertionally inactivated at the
      chromosomal level, with an antibiotic resistance marker. The analysis of this
      mutation in wild type and pts- backgrounds, indicated that B. subtilis has no
      other pyruvate kinase activity capable of complementing the absence of PykA.

PMID- 10932723
TI  - Cholera in north Brazil: on the occurrence of strains of Vibrio cholerae O1 which
      fail to ferment sucrose during routine plating on thiosulphate-citrate-bile salt
      sucrose agar (TCBS). A new problem in diagnosis and control?
AB  - The occurrence is recorded from a biochemical strain variant of Vibrio cholerae
      O1 originating from the municipality of Oiapoque, Amapa State, north Brazil and
      responsible for an epidemic outbreak of cholera in that region in August, 1994.
      The principal characteristic of the strain is its incapacity of break down
      sucrose on T.C.B.S. agar plates, and its delayed utilization of that sugar only
      after 48 hs. when cultivated in liquid medium. The strain spread rapidly in north
      Brazil, becoming responsible for most of the cases of cholera reported in
      Amazonian Brazil. The importance of this observation in laboratory diagnosis and
      the control of cholera is discussed.

PMID- 10932724
TI  - Frequency of adhesive factors and enterotoxins in strains of Escherichia coli
      isolated from piglets with diarrhea.
AB  - Neonatal colibacillosis is one of the most prevalent illnesses in pig farms. In
      order to examine the frequency of adherence factors and the production of
      enterotoxins in strains of E. coli, we collected stool specimens from 500 piglets
      between 1 and 10 days of age with diarrhea, including piglets from several
      different farms on the periphery of Merida, Yucatan. One thousand and eighty
      (1080) strains of E. coli were isolated, of which 127 (11.76%) produced STa, and
      62 (5.74%) produced adherence factors. Of these, 30 (48.39%) produced factor K88,
      18 (29.03%) produced factor 987P, 12 (19.35%) produced K99, and 2 (3.23%)
      produced F41. Of the 62 strains which produced adherence factors, 42 (67.74%)
      also produced STa, and of these, 17 (40.84%) produced factor K88, 13 (30.95%)
      produced 987P, 10 (23.81%) produced K99, and 2 (4.76%) produced F41. In summary,
      of the 1080 strains isolated, 42 (3.89%) produced both STa toxin and adherence
      factors, 85 (7.87%) produced STa but did not produce adherence factors, and 933
      (86.39%) produced neither STa or adherence factors. No LT-producing E. coli was
      detected in this study.

PMID- 10932725
TI  - A simple procedure for determining the presence and concentration of Listeria
      monocytogenes in dairy products.
AB  - This paper presents a simple method for determining both the presence and
      concentration of Listeria monocytogenes in dairy products. The method involves
      application of the Most Probable Number (MPN) technique and enrichment of a 25 g
      sample. Our tests showed that the MPN correlates with the Colony Forming Units
      (CFU), and estimated concentrations of as low as 1 bacterium/gr or less. We also
      studied the influence of Listeria innocua as an accompanying flora. We detected
      L. monocytogenes, even in the presence of concentrations of 4 times as much L.
      innocua. Nonetheless, L. monocytogenes could not be detected when the
      concentration of L. innocua surpassed 90%.

PMID- 10932726
TI  - Hemolysins and verotoxin (VT) in enteric Escherichia coli isolated from pigs.
AB  - One hundred and three E. coli strains isolated from the intestinal contents of
      pigs were examined for hemolysis and verotoxin production on Vero monolayer
      cells. Hemolysins were produced by 18 (17.5%) strains;--hemolysin was produced by
      6 strains of which 4 belonged to serotype O149:K91, K88ac;--hemolysin was
      produced by 8 strains which could no be serotyped; 1 strain produced-hemolysin
      and possessed fimbrial antigens K88; the remaining 3 strains were enterohemolytic
      and VT producers. Among the 85 non-hemolytic strains, 11 showed some antigenic
      properties. Only 3 could be serotyped (O64:K 'V142'; O157:K 'V17' and O149:K91);
      4 had fimbrial antigens K88 and 1 strain was K99, and 3 possessed capsular
      antigen (K89). According to these results it is possible to conclude that both
      hemolytic and non-hemolytic E. coli strains could be pathogenic.

PMID- 10932727
TI  - [Respiratory oxidases: the enzymes which use most of the oxygen which living
      things breathe].
AB  - The respiratory oxidases are the last enzymes of the aerobic respiratory chain.
      They catalize the reduction of molecular oxygen to water, with generation of an
      electrochemical gradient useful for the energy demanding cellular processes. Most
      of the oxidases belong to the heme-copper superfamily. They possess a heme-copper
      center, constituted of a high spin heme and a CuB center, where the reduction of
      oxygen takes place and probably where the link to proton pumping is located. The
      superfamily is divided in two classes: the quinol- and the cytochrome c-oxidases.
      The latter are divided in the aa3 and the cbb3-type cytochrome c oxidases. The
      main difference between quinol- and the aa3-type cytochrome c-oxidases is the CuA
      center, which is absent in the quinol oxidases. The cbb3-type cytochrome oxidases
      have the binuclear center, but lack the CuA center. They also does not have the
      classical subunits II and III. These differences seem not to affect the oxygen
      reduction or the proton pumping. Probably the oxidases have evolved from some
      denitrification enzymes and prior the photosynthetic process. Also is possible
      that the cbb3-type cytochrome oxidases or others very similar have been the first
      oxidases to appear.

PMID- 10932728
TI  - Association between hemolytic uremic syndrome and verotoxin-producing strains of
      E. coli.
AB  - One of the most frequent etiologic agents of Hemolytic Uremic Syndrome (HUS) is
      Escherichia coli O157H7, a microorganism that possesses virulence factors (Shiga
      like Toxins I and II and adhesion fimbriae). The present study was set up to
      determine the relationship between HUS and the presence of Verotoxin in patients
      of "Nino Jesus" Children's Hospital. Tucuman, Argentina. 19 Children between 0
      and 4 years old suffering from HUS (typical and atypical symptoms) and 15 control
      children of similar sex and age were selected. Presence of enterohemorrhagic E.
      coli was studied in both groups using molecular hybridization techniques. Free
      Verotoxin and Verotoxin-producing E. coli were analyzed in Vero cells. The
      following results were obtained: 1) The cytotoxic effect on Vero cells from fecal
      filtrates was observed in all children suffering from HUS 2) Verotoxin-producing
      E. coli was detected in only 12 of them 3) None of the filtrates of feces from
      control children presented a cytotoxic effect on Vero cells 4) In 8 of the
      patients suffering from HUS serotype O157H7 was isolated, in one O55K59 and in 3
      typification of E. coli was not possible with the serums assayed 5) 77.5% of the
      strains isolated from HUS patients gave a positive molecular hybridization
      reaction, showing the following: Adhesion Fimbriae (AF) (25%); AF + Shiga-like
      Toxin I (13.75%); AF + Shiga-like Toxin II (20%); AF + Shiga-like Toxins I and II
      (41.25%). In patients suffering from atypical HUS a combination of AF + Shiga
      like Toxins I and II was found. The 15 control children did not hybridize to the
      probes assayed. From the results obtained we may conclude that there exists a
      relationship between HUS and the presence of Verotoxin in the children suffering
      from HUS studied. The predominant serotype in our cases was O157H7 and Shiga-like
      Toxin II was found with highest frequency.

PMID- 10932729
TI  - Symptomatic bacteriuria due to Ureaplasma and Mycoplasma in adults.
AB  - 314 women, and 52 men were screened during 18 months, for the presence of
      Ureaplasma urealyticum and Mycoplasma hominis in a midstream specimens of urine.
      All the patients were adults with symptoms of urinary tract infection who
      consulted a physician at a Primary Health Center "Jose Castro Villagrana" in
      Tlalpan, D.F. Mexico. Ureaplasma urealyticum was isolated in 54 (17.1%) of the
      women and 8 (15.4%) of the men. Only Escherichia coli and Gardnerella vaginalis
      were isolated more frequently in both groups, 36.6% and 25.4%, respectively in
      women and 58.5% and 30.8% in men Mycoplasma hominis was isolated in 12 (3.8%) in
      women and 4 (7.7%) in men. The bacteriuria due to fastidious bacteria or
      Ureaplasmas that is not detected by routine culture methods are relatively common
      and would not necessarily respond to antibiotic treatment for conventional
      urinary tract pathogens.

PMID- 10932730
TI  - Fungal agents isolated from cancer patients.
AB  - With the aim to know the frequency of mycotic agents in patients with different
      types of cancer, samples were obtained from 81 patients from the Hospital de
      Oncologia, Centro Medico Nacional Siglo XXI, IMSS from May 1995 through May 1996.
      In a conventional grouping seven (7) ambulatory patients were found in early
      stages, twenty seven (27) occasionally hospitalized patients were found in
      intermediate stage and forty seven (47) hospitalized patients in terminal stage
      of cancer. The different samples were processed through routine mycologycal
      methods and the following fungi species were isolated and identified: fifty four
      strains (58%) of Candida albicans followed by eleven strains (11.8%) of Candida
      tropicalis, six strains (6.45%) of Candida parapsilosis, five strains (5.37%) of
      Candida krusei, four strains (4.3%) of Candida humicola and five strains (5.37%)
      of Rodothorula rubra. From medical devices like catheter tips, drainage catheters
      (Pen rouse, Foley) and gallbladder catheters; four (4) strains of C. albicans,
      three (3) strains of Rodothorula rubra and two (2) strains of Aspergillus sp were
      isolated. Of the Candida non albicans it was relevant to find C. krusei more
      frequently than Rodothorula rubra, Aspergillus sp and Penicillum sp. The
      frequency of the presence of fungi increases commensurately to the advancement of
      the clincal stage of the cancer.

PMID- 10932731
TI  - [Poisoning by enterotoxin from Staphylococcus aureus associated with mocha
      pastry. Microbiology and epidemiology].
AB  - A brief description of a foodborne outbreak due to S. aureus enterotoxin
      associated with the consumption of mocha cake in the city of Guadalajara is
      presented. The cake was prepared in a bakery and affected nearly 100 persons. S.
      aureus was isolated from the nose and skin of one of the pastry cooks. A S.
      aureus strain isolated from the cake involved in the outbreak was not only unable
      to grow in the mocha cream, but it actually decreased in numbers by 2 log after
      72 h of storage at 30 degrees C. The pH of mocha cream ranged from 6.2 to 6.6,
      and water activity from 0.833 to 0.859, with a media of 0.841. In preparing mocha
      cake at the shop, one half of the dough used to be sprayed with a sucrose
      solution in water (20% w/v); mocha cream was spread on the other half of the
      dough before overlapping the two halves. When mocha cake was prepared in this
      manner, and stored at 30 degrees C, S. aureus increased in number by more than 4
      log after 48 h. S. aureus did not grow in the cake stored at 4-7 degrees C.
      Contributory factors in this outbreak were an increase of water activity in the
      interphase of the mocha and the cake dough, storage of the cake in an
      unrefrigerated area, and an unusually high ambient temperature (28-32 degrees C)
      at that time.

PMID- 10932732
TI  - [Identification of caprine arthritis encephalitis virus using histopathological,
      immunohistochemica, and ultrastructural examination of tissues from seropositive
      goats in Mexico].
AB  - This study demonstrated the presence of viral particles suggestive of arthritis
      encephalitis virus through the clinic, serologic, pathologic, immunohistochemic
      and ultrastructural studies in dairy goats. In the postmortem studies the tissues
      used were: synovial membrane, lungs and mammary gland from goats with clinical
      signs characteristic of the disease and positive for serum antibodies to the
      virus.

PMID- 10932733
TI  - Use of a duplex PCR/DNA probe assay to monitor Babesia bovis and Babesia bigemina
      in cattle during a vaccination trial.
AB  - A Duplex Polymerase Chain Reaction (DPCR)/DNA probe assay was used to detect
      Babesia bovis and B. bigemina DNA in cattle undergoing immunization trials. Blood
      samples were collected from 15 non-splenectomized, 1-2 years old bulls,
      inoculated with 1 x 10(7) each of culture-derived B. bovis- and B. bigemina
      infected erythrocytes. 15 bulls inoculated with normal erythrocytes served as a
      control group. All cattle were field exposed to tick-transmitted Babesia 21 days
      (20 animals, Group I) and 60 days (10 animals, Group II) post-inoculation (PI).
      After immunization, the DPCR/DNA probe assay detected B. bigemina and B. bovis
      parasite DNA in all inoculated animals from days 4 to 14 PI. At challenge, B.
      bovis DNA was detected in all control animals as early as day 8 (Group I), or day
      11 (Group II) post-introduction to a tick-infested area. The immunized bulls
      showed B. bovis positive PCR/DNA probe signals from day 0 (Group II) and day 8
      (group I), up to day 32 post-exposure to ticks. Positive B. bigemina signals were
      detected from day 0 (Group I) and day 8 (Group II), up to day 36 post-exposure to
      ticks. During challenge, it was not possible to clearly define whether the
      PCR/DNA probe signals detected in the blood from immunized cattle were a result
      of amplified DNA from the culture-derived parasites, from the tick-transmitted
      parasites, or both.

PMID- 10932734
TI  - Arsenic resistance determinants from environmental bacteria.
AB  - Arsenic resistance determinants from 42 environmental bacterial isolates (32 Gram
      negative) were analyzed by DNA: DNA hybridization using probes derived from
      Escherichia coli and Staphylococcus plasmid or chromosomal arsenic resistance
      (ars) genes. In colony hybridization assays, 11 and 1 Gram negative strains
      hybridized with the E. coli chromosome and plasmid probes, respectively. No
      hybridization was detected using a probe containing only the arsA (ATPase) gene
      from E. coli plasmid or with a Staphylococcus plasmid ars probe. From Southern
      hybridization tests of some of the positive strains it was concluded that
      homology to ars chromosomal genes occurred within chromosome regions, except in
      an E. coli isolate where hybridization occurred in both the chromosome and a 130
      kb plasmid. Our results show that DNA sequences homologous to E. coli ars
      chromosomal genes are commonly present in the chromosomes of environmental
      arsenic-resistant Gram negative isolates.

PMID- 10932735
TI  - [Bacterial systems for expelling toxic metals].
AB  - Bacteria have developed diverse resistance strategies towards toxic metals with
      which they interact in the environment. The mechanisms of tolerance include
      extracellular precipitation, sequestration by cell envelopes, intracellular
      accumulation, redox transformations and membrane efflux systems. Genes
      responsible for these processes may be encoded by the chromosome or by plasmids.
      Since some toxic metals are also essential micronutrients (i.e. copper, cobalt,
      zinc, nickel), bacteria must precisely adjust the functioning of uptake and
      efflux systems to maintain their adequate intracellular levels. In the case of
      metals with no biological function (i.e. cadmium, silver), transport systems must
      be oriented only to the extrusion of the toxic ions. In the last few years,
      several bacterial systems devoted to the efflux of toxic metals were analyzed at
      the molecular level resulting in a detailed understanding of the biochemical
      mechanisms of resistance. Among these are the membrane pathways that extrude
      cations derived from copper, cadmium, zinc, nickel, cobalt and silver. Two
      general mechanisms have been found: those involving P-type ATPases, and some
      using proton antiporter systems.

PMID- 10932736
TI  - Glutathione S-transferase in helminth parasites.
AB  - Glutathione S-transferases (GSTs; EC 2.5.1.18) are a large family of
      multifunctional dimeric enzymes that conjugate reduced glutathione to
      electrophilic centers in hydrophobic organic compounds. The GST enzymatic
      activity has been described in the adult and larval stages of helminths. Several
      forms and isoforms of the enzyme have been purified and GST genes have also been
      isolated and expressed as recombinant proteins. The helminth GSTs participate in
      detoxification of lipid hydroperoxides and carbonyl cytotoxics produced by oxygen
      reactive intermediates (ORI). The ORIs can come from the endogenous parasite
      metabolism or from the host immune system. The helminth GSTs are able to
      conjugate glutathione to xenobiotic compounds or to bind to anthelminth drugs.
      GST is usually localized near to host-parasite interface. This enzyme has been
      identified as a potentially vulnerable target in immunotherapy and chemotherapy.
      The present review compiles current knowledge about the biochemical
      characteristics of the enzyme, its presence, localization, induction, structural
      heterogeneity, relationship with mammalian GSTs, detoxification capacity and
      ability to induce protection in several animal models.

PMID- 10932737
TI  - [Microbial sources of pigments].
AB  - Pigments from natural sources has been obtained since long time ago, and their
      interest has increased due to the toxicity problems caused by those of synthetic
      origin. In this way the pigments from microbial sources are a good alternative.
      Some of more important natural pigments, are the carotenoids, flavonoids
      (anthocyanins) and some tetrapirroles (chloropyls, phycobilliproteins). Another
      group less important are the betalains and quinones. The carotenoids are
      molecules formed by isoprenoids units and the most important used as colorant are
      the alpha and beta carotene which are precursors of vitamin A, and some
      xantophylls as astaxanthin. The pigment more used in the industry is the beta
      carotene which is obtained from some microalgae and cyanobacteria. The
      astaxanthin another important carotenoid is a red pigment of great commercial
      value, and it is used in the pharmaceutical feed and acuaculture industries. This
      pigments is mainly obtained from Phaffia rhodozyma and Haematococcus pluvialis
      and other organisms. The phycobilliproteins obtained from cyanobacteria and some
      group of algae, have recently been increased on the food industries. In the last
      years it has been used as fluorescent marker in biochemical assays. Our research
      group have carried out studies about the factors that improve the production of
      these pigments obtained from different microbial species as well as the methods
      for their extraction and application.

PMID- 10932738
TI  - [Biosynthesis of congeners during alcohol fermentation].
AB  - The flavor of alcoholic beverages is a consequence of a complex mixture of many
      compounds, including small concentrations of some volatile metabolites known as
      congeners, which are produced by the yeast during the fermentation. The more
      important compounds are those that can be found in all the alcoholic beverages in
      different concentrations, and they can be grouped on the following chemical
      species: higher alcohols, esters, and carboniles. In the current paper the
      biochemical pathways that produce these compounds from the raw materials are
      reviewed. Research done in this field has led to a more complete knowledge
      concerning to organoleptic profiles of alcoholic beverages and to a better
      control for the production of the final product.

PMID- 10932739
TI  - Action against Vibrio cholerae O1 Tox+ of chemical products used in the lemon
      production.
AB  - Tucuman is the first lemon exporting province in Argentina and the fourth lemon
      exporter in the world. The present work was set up to study the survival of
      Vibrio cholerae O1 Tox+ after application of different chemical products used in
      the lemon production (from its cultivation until its packing). The following
      products were studied: copper oxychloride, benomil (a carbamate), active
      chlorine, sodium-o-phenylphenoate, guazatine (a polyamine mixture), imazalil (an
      imidazole) and fresh and dehydrated lemon peel. Using different dilutions of the
      products above mentioned antimicrobial tests were carried out with different
      exposure times against V. cholerae Serogroup O1, Biotype El Tor, Serotype Inaba.
      The microorganism was used at concentrations of 10(2), 10(4), 10(6) and 10(8) CFU
      ml-1, the latter one being considered as an infectious dose. The following
      results were obtained: 1) Active chlorine (chlorinated water) showed bactericidal
      activity at concentrations of 0.5 x 10(-1), 10(-1), y 2 x 10(-1) g l-1 after 10
      min of exposure time. 2) Copper oxychloride, sodium-o-phenylphenoate, guazatine
      and imazalil showed bactericidal activity against V. cholerae at concentrations
      of 10(2) and 10(4) CFU ml-1. 3) Due to the fact that the fruit is successively
      sprayed with several chemical products during its cultivation, it could be
      proposed that the result of the successive treatments is superior to the result
      of a treatment with each of the individual products. This consideration should be
      taken into account when evaluating the eventual protection of the lemon.

PMID- 10932742
TI  - Functional Bradyrhizobium japonicum NifA expression under a hybrid nptII-nifH
      promoter in E. coli and Acetobacter diazotrophicus SRT4.
AB  - A hybrid promoter consisting of the in tandem fusion of the Tn5 nptII and the
      Klebsiella pneumoniae nifH promoters was constructed to study the functionality
      of the nif genes transcriptional activator NifA from Bradyrhizobium japonicum in
      two different host bacteria. beta-galactosidase experiments in E. coli revealed
      that the hybrid nptII-nifH promoter can behave as a constitutive or a NifA
      inducible promoter depending on the aeration conditions. Expression of the B.
      japonicum NifA from the hybrid nptII-nifH promoter (plasmid pBPF204) induced "in
      trans" lacZ transcription from the Azotobacter chroococcum nifH promoter in E.
      coli and A. diazotrophicus cells grown at low pO2. Similarly, the plasmid pBPF204
      increased nitrogenase activity in A. diazotrophicus cells grown under
      microaerobic conditions. Based on these results, we suggest that the B. japonicum
      NifA could function as an efficient O2-sensitive transcriptional activator of nif
      genes in genetically distant diazotrophic bacteria.

PMID- 10932741
TI  - Effect of beta-lactamase inhibitors on minimum inhibitory concentration of
      ampicillin and amoxicillin for Staphylococcus aureus strains.
AB  - Seventy strains of Staphylococcus aureus isolated from the nasopharynx (80%),
      urinary tract (16%), skin (1 strain) and eyes (2 strains) of patients at the
      clinical laboratory "El eritrocito" were analyzed. Susceptibility to 12
      antibiotics was tested by the method of Kirby-Bauer. Minimal inhibitory
      concentration (MIC) of ampicillin, ampicillin + sulbactam, amoxicillin and
      amoxicillin + clavulanic acid were determined by plate dilution. Percentages of
      resistance were: Penicillin and ampicillin (100%), ceftazidime (81.4%),
      erythromycin (68.6%), tetracycline (31.4%) trimethoprim-sulphametoxasol (25.7%),
      dicloxacillin and pefloxacin (12.8%), cefuroxime and cefotaxime (4.3%),
      gentamicin (2.8%), cephalothin (0%). All strains were resistant to three or more
      antibiotics, with higher percentages of resistance to four (31.4%), three
      (27.1%), five (21.4%) and six (12.9%) drugs. One strain was resistant to nine
      antibiotics and 5.9% were resistant to seven. 97.5% of the strains were beta
      lactamase-positive. The MIC50 of ampicillin and amoxicillin was 500 micrograms/ml
      and the MIC90 were 1727 micrograms/ml and 2000 micrograms/ml, respectively. beta
      lactamase inhibitors sulbactam and clavulanic acid reduced these values
      eightfold, except for the MIC50 of ampicillin + sulbactam whose reduction was
      sixteen fold. These results show that the combination of beta-lactamic + beta
      lactamase inhibitor was more efficient than cephalosporins for killing these beta
      lactamase-positive strains.

PMID- 10932740
TI  - Serological activity of white-tail deer against several species of Brucella.
AB  - In Mexico, brucellosis is a widely distributed disease of domesticated ruminants,
      but its frequency in wild ruminants has not been documented. Since northeast
      Mexico is the main distribution area of white-tailed deer and has been reported
      as an area positive for brucellosis in domesticated species, the present study
      was conducted in order to determine serological activity against several species
      of the genus Brucella in white-tailed deer. A total of 208 sera of white-tailed
      deer were collected during the springs of 1994 and 1995 in the north part of the
      states of Nuevo Leon and Coahuila. Each serum was analyzed for the detection of
      antibodies against two smooth (B. abortus and B. melitensis) and one rough (B.
      ovis) species of the genus Brucella. The serological tests used for the
      determination of the presence of antibodies against Brucella were card and plate
      agglutination for B. abortus, plate agglutination and rivanol precipitation for
      B. melitensis, and agar gel immunodiffusion for B. ovis. Each assay had positive
      and negative controls. None of the analyzed samples was found to be positive, and
      only two sera showed partial plate agglutination against B. melitensis at a
      dilution of 1:25; however, at higher dilutions and to the rivanol precipitation
      test the same samples were negative. Therefore, the percentage of positive sera
      was estimated at 0% (0/208). This result makes evident the absence of positive
      white-tailed deer against Brucella in the sampled area, despite that this disease
      is considered present in domesticated species. Therefore, white-tailed deer does
      not have, at the present time, an important role for the dispersion of the
      disease. The same result has been reported in other countries.

PMID- 10932743
TI  - Identification of bacteria in water for pharmaceutical use.
AB  - Different systems for the obtention of water used in Biopharmaceutical Industry
      were characterized from the bacteriological point of view. Determination of
      aerobic mesophilic microorganisms was performed; as well as the isolation of
      contaminant microorganisms for what the techniques of membrane filtration was
      used. For the identification of the more representative species there were made
      conventional biochemical tests and quick systems: API. The results show that
      water serving as tap water for purification systems fulfill with the
      microbiological requirements to this kind of water. All the isolated
      microorganisms were gram-negative bacteria characteristics of this environment:
      Pseudomonas putida, Xanthomonas maltophilia, Aeromonas salmonicida ssp.
      salmonicida, Flavimonas coryzihabitans and Acinetobacter iwoffi. The
      ultrafiltration and distillation tested systems fulfill with the established
      microbiological limits, except for deionization and distilled water storing
      systems. The isolation showed that approximately the 76.9% were of Gram-negative
      bacteria, the 14.6% of Gram-positive cocci and the 8.5% Gram-positive sporulated
      bacilli. The most representative genus of purified water were: Pseudomonas, with
      the higher percent of incidence, Staphylococcus, Bacillus, Flavobacterium,
      Sphingomonas, Aeromonas and Agrobacterium.

PMID- 10932744
TI  - A review on the use of microorganisms as probiotics.
AB  - A literature review on the use of live microorganisms as probiotics is presented.
      Topics discussed are the definition of probiotic; the normal microflora of the
      digestive system of mammals, including bacterial interactions in the gut,
      colonization, modification of metabolic processes, and immunostimulation.
      Probiotics studies in humans and in farmed animals, with special emphasis on the
      use of Lactobacillus spp. and Bifidobacterium spp. are also discussed.

PMID- 10932745
TI  - Serological survey of canine borreliosis.
AB  - Lyme disease or Borreliosis, a tick-borne disease caused by Borrelia burgdorferi,
      has been described recently in dogs. A total of 850 blood samples were obtained
      from dogs in the metropolitan area of Monterrey, Mexico. An indirect
      immunofluorescent assay (IFA) was used to detect antibodies against Borrelia
      burgdorferi, the etiologic agent of Lyme disease in human beings. The 16% (136)
      of these dogs had positive results. These findings suggest that exposition to
      this microorganism is common in dogs in this area and that this disease is of
      importance to veterinarians.

PMID- 10932746
TI  - Behavior of enterotoxigenic strains of Staphylococcus aureus in milk fermented
      with a yogurt starter culture.
AB  - The ability of a yogurt starter culture formed by Streptococcus salivarius subsp.
      thermophilus and Lactobacillus delbrueckii subsp bulgaricus to inhibit the growth
      of four enterotoxin type A and B producers Staphylococcus aureus strains (ATCC
      6538, S6, FRI-100 and a strain isolated from milk) during fermentation of milk
      and subsequent storage was investigated. Sterile skim milk was inoculated with
      about 10(6) CFU/ml of S. aureus and with about 10(6) CFU of starter culture, and
      incubated at 42 degrees C during 8 h, followed by refrigeration at 4 degrees C.
      Samples were taken every 2 h during fermentation and every 2 days during storage.
      Viable count of lactic acid bacteria and S. aureus as well as pH, acidity,
      thermostable deoxyribonuclease (TNase) and staphylococcal enterotoxin A (SEA)
      production were evaluated. Behavior of four strains was similar; S. aureus
      survived the 8 h fermentation with LAB, and its population began to decrease from
      the first day of storage, being completely inhibited at 9-10 days. TNase and SEA
      production were positive in all samples taken along the study. It was
      demonstrated that enterotoxigenic strains of S. aureus were able to survive the
      fermentation of milk with a yogurt starter culture and they were inhibited after
      several days during storage of the fermented product, contrary to the general
      belief which considered it very difficult due to the low pH. Even though S.
      aureus was inhibited, TNase and SEA were demonstrable along the storage.
      Therefore, fermented milks may play an important role in the transmission of this
      organism.

PMID- 10932747
TI  - [Application of gas chromatography in the identification of Enterobacter cloacae,
      Enterobacter aerogenes, and Enterobacter agglomerans].
AB  - Enterobacter cloacae, Enterobacter aerogenes and Enterobacter agglomerans were
      identified using gas chromatography as a substitution of the traditional
      techniques. Their acid methyl esters profiles were determined using a gas
      chromatograph Hewlett Packard 5890A and a RSL-150 heliflex capillary column. A
      total of 120 samples were analyzed from reference strains (ATCC 13047, 13048,
      27155) and environmental isolations, eleven fatty acids were included in the
      profiles from which cis-9, 10-methyleneoctadecanoic acid (peak 24), cis-9
      hexadecenoic acid (peak 14), octadecanoic acid (peak 23) and dodecanoic acid
      (peak 3), were the most important for the differentiation of the three species
      analyzed.

PMID- 10932749
TI  - [Phagocytic activity of polymorphonuclear leukocytes of pregnant women].
AB  - Cellular and humoral immunity are depressed during pregnancy, for this reason the
      non-specific immunity mediated by polymorphonuclear leukocytes plays an important
      role in the defense against bacterial infections. The objective of this study was
      evaluate the phagocytosis, phagocytic index (particles ingested average by cell)
      and nitroblue tetrazolium reduction (NBTr) in three trimesters of pregnancy. The
      phagocytosis and rNBT assays were carried out by means of adherence on surface of
      the glass. The resulted showed that phagocytosis, phagocytic index and NBTr were
      normal in two first trimesters of pregnancy compared with nonpregnant women
      group. However, phagocytosis and phagocytic index were significantly decrease (p
      < 0.05) in the third trimester pregnancy. This phagocytosis deficiency possibly
      explains the increase of respiratory infections, diarrhea disease and
      bacteriuria. Several factors could be responsible of this non-specific immunity
      depressed during pregnancy. Further studies are necessary to define the
      biological significance of this immunosuppression.

PMID- 10932748
TI  - Bacterial vaginosis a "broad overview".
AB  - Bacterial vaginosis (BV) was first reported in 1995 by Gardner and Dukes, who
      described the unique clinical signs and symptoms and the distinctive nature of
      the vaginal discharge associated with it. They also described a "new" causative
      organism, which they named "Haemophilus vaginalis", subsequently renamed
      Gardnerella vaginalis. BV is currently the most prevalent cause of infectious
      vaginitis among women attending for genitourinary diseases. BV has a complex
      microbiology. Lactobacillus populations, which are usually dominant in healthy
      women, are replaced by a polymicrobial group of organisms that includes G.
      vaginalis, anaerobic Gram-negative rods such as Prevotella species,
      Peptostreptococcus species, Mycoplasma hominis, Ureaplasma urealyticum, and often
      Mobiluncus species. Anaerobic bacteria produce enzymes, aminopeptidases, that
      degrade protein and decarboxylases that convert amino acids and other compounds
      to amines. Those amines contribute to the signs and symptoms associated with the
      syndrome, raising the vaginal pH and producing a discharge odor. The excessive
      amounts of bacteria characteristic of the syndrome attach to epithelial cell
      surfaces, resulting in "clue cell". Nearly half the patients report no noticeable
      symptoms, but many develop a characteristic copious, malodorous discharge if
      untreated. Results from epidemiologic studies have associated BV with serious
      upper genital tract infections and adverse pregnancy outcome. In particular, the
      presence of BV in pregnant women increases the risk of preterm delivery, and
      evidence is now compelling that BV is a cause of preterm delivery. The interest
      in potential invasiveness of G. vaginalis has increased. However, virulence
      determinants have not been studied enough. The most important therapy includes
      clindamycin and metronidazole.

PMID- 10932750
TI  - [Dichotomous keys for identifying Staphylococcus isolated from bovine milk].
AB  - Many efforts have been done in order to identify species of Gram positive and
      catalase positive coccus isolated from raw milk. The aim of this epidemiological
      observation, was to identify different strains isolated from raw milk according
      to conventional criteria and to recommend a useful and practical methodology for
      their correct identification. Gram positive and catalase positive coccus were
      tested for bacitracin resistance, novobiocin susceptibility, coagulase and others
      tests (e.g. carbohydrate fermentation). Dichotomic keys were designed to typify
      Staphylococcus' species. They were grouped into: Group I, coagulase positive,
      novobiocin susceptibility; Group II coagulase negative novobyocin resistance; and
      Group III coagulase negative novobiocin susceptibility. 62 strains were tested
      and S. hycus (17.7%) was the most isolated species, S. aureus (14.5%), S. sciuri
      (12.9%) and S. haemolyticus (11.3%) were also isolated. S. epidermidis was not
      isolated.

PMID- 10932751
TI  - Search for antiviral activity of certain medicinal plants from Cordoba,
      Argentina.
AB  - The antiviral activity of alcoholic extracts of several species belonging to the
      Asteraceae, Labiatae, Plantaginaceae, Schizaceae, Umbelliferae, Usneaceae and
      Verbenaceae families has been studied. The tests were carried out in Vero celis
      pseudorabies virus strain RC/79 (herpes suis virus) system. Eight plant extracts
      (Achyrocline satureioides, Ambrossia tenuifolia, Baccharis articulata, Eupatorium
      buniifolium, Mynthostachys verticillata, Plantago brasiliensis, Plantago mayor L
      and Verbascum thapsus) were able to inhibit at least 2 log, the viral
      infectivity.

PMID- 10932752
TI  - [Serotyping of strains of Serpulina hyosenteriae isolated form swine with porcine
      dysentery symptoms in the province of Buenos Aires].
AB  - Seventeen Serpulina hyodysenteriae strains isolated from faeces, rectal swabs and
      intestinal contents of pigs with Swine Dysentery, from farms located in Buenos
      Aires province were serotyped. Samples on selective media (trypticase soy agar
      added by 5% ovine blood, 400 mg/l spectinomicin, 30 mg/l colistin, 30 mg/l
      vancomycin) were streaked and incubated under anaerobic atmosphere for 72 h at 42
      degrees C. Suspected S. hyodysenteriae growth were identified by strong beta
      hemolytic zone, without colonies, and the spirillar morphology, using the
      Victoria Blue 4-R stain were criteria following by S. hyodysenteriae preliminar
      identification. The following antigens were made by phenolic extraction from a
      concentrated inocula washed twice in PBS pH 7: whole-cell (WC), boiled cell (BC)
      and lipopolysaccharide (LPS). Two serological test were: coagglutination and
      immunodiffusion, using polyclonal rabbit antisera against the 9 serotypes of S.
      hyodysenteriae and S. innocens, using WC and BC like antigens for the first test
      and BC and LPS for the second. The Dot-ELISA Test was performed using BC and LPS
      antigens and monoclonal antibodies (AbM) against serotypes 1, 2, 3, 8, 9 of S.
      hyodysenteriae, AbM species-specific and AbM against S. innocens. All isolated S.
      hyodysenteriae strains belonged to serotype 8. Like in other countries occurred,
      it would exit a high regional prevalence of S. hyodysenteriae serotype, being the
      serotype 8 in Argentine.

PMID- 10932753
TI  - Evaluation of the antimicrobial susceptibilities of coagulase-negative
      staphylococci by E-test.
AB  - Coagulase-negative staphylococci (CoNS) have recently emerged as important
      nosocomial pathogens. In this study, the susceptibility of 53 isolates of CoNS
      (42 S. epidermidis, 6 S. haemolyticus, 3 S. caprae, 1 S. lugdunensis and 1 S.
      chromogenes) obtained over a 1 year period at a Brazilian Hospital were tested
      for vancomycin, teicoplanin, cephalothin, penicillin, oxacillin, and
      chloramphenicol. The minimal inhibitory concentration (MICs) were determined by
      the E-test using saturated swabs or the flooding method. No isolates showed
      resistance to vancomycin, 3 (5.7%) were resistant to teicoplanin, 5 (9.4%) to
      cephalotin, most of them, (47, 88.6%) were resistant to penicillin, 19 (35.8%) to
      oxacillin and 27 (50.9%) to chloramphenicol. The study shows that the increased
      resistance of CoNS can cause serious infections of difficult treatment. The E
      test proved to be a convenient and reliable method for MIC determination of CoNS
      isolates and the qualitative and quantitative results obtained by flooding were
      much more reproducible than the results obtained using swabs.

PMID- 10932754
TI  - A serological survey of leptospirosis in sheep in Chile.
AB  - In order to investigate exposure to Leptospira spp. in sheep in the Xth Region in
      the south of Chile, 629 ovine serum samples were collected from 11 convenience
      selected sheep farms, using within farm random sampling. The sera collected were
      examined for antibodies to the following serovars; icterohaemorrhagiae,
      autumnalis, hardjo, pomona, ballum, and canicola, using the Microscopic
      Agglutination Test. Ten out of eleven flocks had sheep which were seropositive
      for at least one Leptospira spp. Positive tests, the majority at low titres, were
      obtained from 36/629 (5.7%) of all the serum samples tested. The most frequently
      detected serovars were, in descending order: icterohaemorrhagiae, autumnalis and
      hardjo. The greatest proportion of positive samples came from sheep which were
      over 30 months old.

PMID- 10932756
TI  - [Mechanisms of pathogenicity and adhesion in Pasteurella haemolytica].
AB  - Pasteurella haemolytica is one of the bacteria most commonly isolated from
      pneumonic cases in ruminants. Some of the mechanisms and factors involved in the
      pathogenesis of the disease are partially documented; and the early stages of
      bacterial colonization have not been totally clarified. Therefore a review is
      presented in this paper, particularly related with the mechanisms of bacterial
      pathogenicity responsible of pulmonary damage to ruminants, as well as a detailed
      analysis of the adherence process.

PMID- 10932755
TI  - [Verification of the proteolytic and lipolytic activities of the microbial flora
      isolated from raw, refrigerated, type B milk. II. Psychrotrophic microorganisms].
AB  - The aim of this work was to evaluate the microbiological quality of raw type B
      milk, kept under refrigeration at 3 degrees C, for a period of 15 days. The milk
      was enumerated and isolated a total of 180 microorganisms, of which 80 were
      psychrotrophics. The ability of these microorganisms to produce lipolysis and/or
      proteolysis in the milk was evaluated. Concerning the microbiological analysis,
      the samples analyzed presented high values for total counting. The results from
      the initial counting were 2.7 x 10(4) UFC/ml for psychrotrophic, with a
      predominance of Gram negative bacilli, which were highly lipolytic and had
      proteolytic activities associated.

PMID- 10932757
TI  - Mastitis outbreak due to Mycoplasma californicum and Mycoplasma canadense in a
      commercial dairy herd in the state of Jalisco, Mexico.
AB  - A commercial dairy herd with 282 cows in lactation suddenly began to have a
      problem with atypical clinical mastitis. The first 28 cases showed severe
      purulent mastitis with hard swollen mammary glands, but without systemic signs of
      illness Some of the cows were lame. The cases were not responsive to antibiotics.
      The evidence suggested that milking machine malfunction and other management
      practices may have contributed to spread infection and to increase the number of
      clinical cases. Culture of milk of the affected cows and bulk tank milk yielded
      mycoplasma colonies that were identified as Mycoplasma californicum and
      Mycoplasma canadense. This is the first isolation and report of these mycoplasmas
      in Mexico and Latin America. The 28 positive cows were segregated and culled;
      however, the owner did not follow the recommendations to sample all the milking
      and dry cows and to implement other preventive measures. Consequently, losses
      were much greater and 177 cows were culled.

PMID- 10932758
TI  - [Antimicrobial resistance among species of Salmonella, Shigella, Escherichia, and
      aeromonas isolated from children with diarrhea in 7 Argentinian centers].
AB  - The increasing levels of resistance of enteropathogenic bacteria against
      antimicrobial agents present geographic variations. We have analysed the
      antimicrobial susceptibility of isolates obtained from 4,364 children under 5
      years of age with acute diarrhea, in 7 cities of Argentina. Diarrheagenic E. coli
      exhibited 74.5% of resistance against ampicillin, 64.2% against sulfametoxazole
      trimethoprim, and Shigella spp., 62% and 75.6% respectively. Salmonella sp.
      showed 35%, 14%, 41.8%, 65.4%, 14.5%, and 13.6% of resistance against ampicillin,
      chloranfenicol, sulfametoxazole-trimetoprim, sulfadiazin, gentamycin, and
      fosfomycin respectively. These values are higher than the ones observed in
      developed countries. Aeromonas showed significantly lower resistance percentage.
      Important differences in our country were observed, consequently, local trials
      should be carried out in order to apply corrective measures.

PMID- 10932760
TI  - [Susceptibility of Biomphalaria glabrata to Schistosoma mansoni from Venezuela
      and Brazil].
AB  - Schistosoma mansoni partially develops its life cycle into snails of the Family
      Planorbid. Biomphalaria glabrata represents an important host-intermediate. This
      paper reports experimental infection with miracidia vs. snail in sympatric and
      parapatric combination. The infection assay to sympatric combination were: BH
      snail (Belo Horizonte, Brasil) vs. a common geographic origin parasite, and
      Barbula, Carabobo State, Venezuela vs. SM Venezuela parasitic. The parapatric
      combination were: BH snail vs. SM; Barbula vs. BH; Caripe Monagas State,
      Venezuela vs. SM and Caripe vs. SM. During the study period was observed not
      miracid penetration. The infection percentage ranged from 88.89% in Barbula vs.
      SM combination to 0.00% in the Caripe vs. BH and BH vs. SM combination. We
      concluded which different existence of susceptibility from evaluated combination.

PMID- 10932759
TI  - Random amplified polymorphic DNA (RAPD) analysis of Paracoccidioides brasiliensis
      isolates.
AB  - Five Paracoccidioides brasiliensis isolates of humans origin were analyzed using
      three arbitrary primers (3301, 3304 and 3307 of 10, 9 and 10 oligonucleotides
      respectively) in random amplified polymorphic DNA (RAPD) analysis. The analysis
      of the complex RAPD profiles obtained were carried out using the Dice similarity
      coefficient that distinguished the isolated Pb 02 from the others (Pb 18, Pb 192,
      Pb 265 and Pb SN). The results revealed limited intraspecific genomic variations
      in these P. brasiliensis isolates and indicate that RAPD can be useful for
      analysis of P. brasiliensis genome for characterization or differentiation within
      this genus.

PMID- 10932761
TI  - [Molecular characterization of rotavirus in the city of Santafe de Bogota,
      Colombia. Determination of the electrophenotypes and typing of a strain by RT
      PCR].
AB  - 131 diarrheic samples obtained from children taken to the emergency room of the
      Misericordia Hospital in Santafe de Bogota were cultivated for rotavirus. These
      virus were found to be etiological agents for the diarrhea in 42 (32%) of the
      patients. In order to characterize electrophoretically the rotavirus they were
      cultured in cell line MA-104, total RNA was extracted and subjected to
      electrophoresis in SDS-PAGE and then the retrotranscription polymerase chain
      reaction. Eight different electrophoretic patterns were found. All patterns
      correspond to group A. Eight positive PAGE samples and the control type RRV were
      cultured in cell line MA-104. Viral growth was found only in the control and four
      of the samples. Total RNA was extracted from all five infected cultures and gene
      9, which codifies for protein VP7 was amplified. All four samples and the control
      were shown to be G3. The finding of eight different electrophoretic types, all of
      them belonging to group A, show a diversity in co-circulating rotavirus strains.
      These findings contribute to a better understanding of viral acute
      gastroenteritis natural history and should help in developing new epidemiological
      vigilance strategies, prevention and control of rotavirus in children population
      of Santafe de Bogota.

PMID- 10932762
TI  - Cellular immune response of intracecally inoculated Mongolian gerbils with
      Entamoeba histolytica trophozoites.
AB  - We analyzed the local and systemic cellular immune response in mongolian gerbils
      inoculated with Entamoeba histolytica. Two groups were intracecally inoculated
      with E. histolytica trophozoites and two groups were used as controls. A
      inoculated groups and a control groups were sacrificed on days 10 and 30 post
      inoculation (p.i), the spleen and mesenteric lymph nodes (MLNs) lymphocytes (Ly)
      were isolated and incubated in vitro with 2 different amebic antigens. The
      proliferative Ly response of inoculated groups was greater than the Ly mitogenic
      response seen in control groups, at day 10 p.i. as well as day 30 p.i. (alpha =
      0.05). Ly response of MLNs was greater in comparison to those of the spleen
      (alpha = 0.05). In other four groups, intradermal reactions with a antigen were
      used to demonstrated delayed hypersensitivity in gerbils after being inoculated
      with E. histolytica trophozoites. The percentage of volume increase of the
      plantar pad swelling were measured. Groups inoculated presented greater increases
      (alpha = 0.05) than groups controls. The evidence presented herein demonstrates
      that the presence of E. histolytica trophozoites in cecum induced a local and
      systemic cellular immune response.

PMID- 10932763
TI  - [A new trichromic safranin stain for the detection of Cryptosporidium parvum,
      Cyclospora cayetanensis, species of Microsporidia and Isospora belli in fecal
      material].
AB  - Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis and Microsporidia
      are frequent pathogens in the immunodeficient host, which may cause multiple
      infections. The above mentioned parasites are found in feces by the application
      of different specific tintorial techniques. The objective of this work was the
      development of a stain for the simultaneous detection of these parasites,
      reducing costs as well as the time taken to make the diagnosis. The safranin
      trichrome stain is simple, chip and its results are similar to those of specific
      tints. All microorganisms are easy to detect and besides being perfectly
      distinguishable from fungi and faecal elements.

PMID- 10932764
TI  - [In vitro predatory activity of 8 fungal isolates against the nematode
      Panagrellus redivivus].
AB  - The aim of this study was to evaluate the predacious capacity in vitro of eight
      isolates of nematophagous fungi: four of Arthrobotrys sp., one of Arthrobotrys
      oligospora, one of Duddingtonia flagrans, one of Dactylaria sp. and one
      Monacrosporium eudermatum. Nine groups of Petri dishes with 13 repetitions each
      were set up. The fungi were seeded in fluor-corn-agar media, following this each
      Petri dish was added with 150 larvae of the free living nematode Panagrellus
      redivivus. Five days after larval addition these were collected by
      Baermannization and were quantified. A significant difference (p < 0.05) between
      all treated group was observed respect with the control. Isolates FTHO-8 D.
      flagrans, R6 M. eudermatum, DAC Dactylaria sp. as well as FTHO-4 and FTHO-6
      Arthrobotrys sp., showed an excellent predatory activity (> 90%) and they could
      be considered as potential bio-control agents in future field trials.

PMID- 10932765
TI  - [In vitro nematophagous capacity of Duddingtonia flagrans maintained under 2
      conditions of preservation].
AB  - One trial was carried out to evaluate the nematophagous capacity of two
      Duddingtonia flagrans cultures, one maintained during one year at laboratory
      temperature and the other one was a recent culture, twelve Petri dishes with
      flour-corn-agar media were seeded with the 1YC another 12 Petri dishes were
      inoculated with the RC. Both were added with 150 larvae/dish of the free living
      nematode Panagrellus redivivus and 12 fluor-corn-agar dishes only with the free
      living nematode were used as a control. The results showed that the nematophagous
      capacity of both cultures were similar but it was statistically different (p <
      0.05) with respect to the control group. It was concluded that the nematophagous
      capacity of D. flagrans was not affected in spite of being kept one year at
      laboratory temperature.

PMID- 10932766
TI  - Four biochemical tests for identification of probable enteroinvasive Escherichia
      coli strains.
AB  - Enteroinvasive Escherichia coli (EIEC) share important features with Shigella
      spp., but EIEC strains are difficult to identify because their biochemical
      reactions are variable, and Sereny tests or other biological and molecular assays
      are expensive or hard to perform. The aim of this work was to detect probable
      enteroinvasive E. coli strains by using four biochemical tests, in children under
      5 years of age with and without acute diarrhea. 330 strains of E. coli isolated
      from children with diarrhea, and 660 strains from children without diarrhea were
      studied. All strains were tested with the following tests: mucus , lysine and
      ornithine decarboxylase and motility. The strains which were negative to the four
      tests were tested by Sereny assay. Twelve strains (3.6%) isolated from children
      with diarrhea were negative to the tests proposed; eleven were lactose positive
      and only one was lactose negative. Three strains (0.5%) from children without
      diarrhea were negative to the tests proposed and were lactose positive. All the
      15 strains (100%) were positive in Sereny assay. We recommend the use of these
      four biochemical tests for initial detection of EIEC strains, because their cost
      is very low and it is feasible carry out them in small diagnostic laboratories.

PMID- 10932767
TI  - [Colibacillosis in swine: proof of vaccine efficacy].
AB  - The damage caused in the economy and animal sanity by the porcine colibacilosis
      are significant and they deserve the investigation of preventive measures that
      give answers to the producers. Existing at the present time approximately 21,000
      pigs in Corrientes and 110,000 in Chaco provinces of Argentine, the losses for
      diarrhea that exterminate whole litters, acquire relevance, specially if they can
      be prevented or cured. For that reason, having 21 strains of enteropathogenic and
      verocitotoxigenic E. coli (ETEC/VTEC) isolated from pigs of the North East of
      Argentine, that were recognized by PCR, two were selected, containing the genes
      for STIa, STIb, LTI, VT2e (SLT-IIv) and F4 (K88). They were spread on nutrient
      agar and Minca medium, to obtain the suspension in PBS, which was inactivated
      with formol. After the sterility and innocuity controls, it was diluted to a 12 x
      10(8) concentration to make the mouse protection test in 20 mice, of 18-20 g,
      inoculating the vaccine the days 1, 4, 7 and 10, by the intraperitoneal route,
      doses of 0.25 ml each one. The day 21 after beginning the test the animals were
      challenged with 50 LD50, and a protection of 85% was obtained. To determine the
      LD50, we prepared a suspension in physiologic solution, corresponding to Mac
      Farland's tube No 10, making dilutions from 10(-1) to 10(-5) and applying the
      statistical method of Reed and Muench. These first results encourage us to
      continue working after a prophylactic measure that were effective, potent and
      elaborated with strains of this area.

PMID- 10932768
TI  - [Prevalence of Chlamydia trachomatis in newborn infants with respiratory
      problems].
AB  - The prevalence of C. trachomatis in neonates with respiratory distress was
      studied after 24 h of birth, nine patients were positive for C. trachomatis
      culture (12.9%). The chest radiographs showed six with hyaline membrane disease
      and two with pneumonia. One patient with treatment of ventilation mechanics
      developed bronchopulmonary dysplasia and was C. trachomatis positive in a second
      cell culture. Of the nine patients with C. trachomatis, eight were neonates
      preterm with low weight to the birth and with leukocytosis. Six patients were
      delivered by cesarean section. These results suggest that C. trachomatis can
      participate in an important way in the development of the distress respiratory in
      infants preterm.

PMID- 10932769
TI  - [Non-fermenting Gram-negative bacilli: distribution in clinical specimens and
      antimicrobial susceptibility].
AB  - In the present work was studied the prevalence, distribution in clinical
      specimens, and antimicrobial susceptibility of non-fermentative Gram-negative
      bacilli (NFGNB) from patients attended at Hospital "Angela I. de Llano"
      (Corrientes, Argentina). A total of 125 strains of NFGNB were recovered from
      various clinical specimens from July, 1997 to December, 1998. Isolates were
      identified by classical biochemical tests. Drug sensitivity was performed by
      standard methods with cefotaxime (CTX), ceftazidime (CAZ), piperacillin (PIP),
      ampicillin-sulbactam (AMS), piperacillin/tazobactam (TAZ), imipenem (IMP),
      amikacin (AKN), gentamicin (GEN) and ciprofloxacin (CIP). The most common
      isolates were Pseudomonas aeruginosa (48.8%); Acinetobacter baumannii (16.8%),
      Acinetobacter spp. (6.4%), Chryseobacterium spp. (5.6%), Stenotrophomonas
      maltophilia (4%), and others (18.4%). Most of them were recovered from
      respiratory secretions (36.0%), and urine (26.4%). IMP was the most effective
      antimicrobial. Many species of NFGNB showed resistance to several antibiotics
      tested (CTX, GEN, AMS, and CIP). Due to multiresistance found by more prevalent
      NFGNB, constant survey of antibacterial sensibility are essential for a correct
      control and management of nosocomial infections, and ambulatory patients with
      some risk factors.

PMID- 10932770
TI  - [Identification of Escherichia coli and coliforms in childhood urinary sepsis
      using CROMOCEN CC chromogenic-fluorogenic medium].
AB  - In the last few years, the use of chromogenic and fluorogenic reactions for the
      identification of the most important pathogens in human urinary tract infections
      has became a powerful tool in clinic diagnostic. The study was carry out in two
      hospitals in Havana City, comparing the performance of experimental medium with
      the traditional one: C.L.E.D. Medium produced by Centro Nacional de Biopreparados
      (BIOCEN). Additional biochemical test were applied (indole, motility, citrate,
      H2S glucose and lactose) for the more accurate identification of different
      strains. During the test 119 positive samples were evaluated with 82 identified
      as E. coli (68.9%). As coliforms 18 samples (15.1%) were identify without any
      biochemical test. The diagnostic sensitivity was 100% and diagnostic specificity
      of new medium was of 97.4% for all assayed samples.

PMID- 10932772
TI  - Role of the calcareous corpuscles in cestode physiology: a review.
AB  - Cysticercosis is a parasitic disease caused by the larval stage or cysticercus of
      the cestode tapeworm Taenia solium. Cysticerci are able to survive in the host
      tissues for long periods in the presence of an immune response. Tissues of
      cestodes contain mineral concretions termed calcareous corpuscles. These
      corpuscles might serve for the focal deposition of exceeding amounts of calcium
      protecting the larvae against calcification. Studies on the morphology and
      composition of calcareous corpuscles in cestodes have resulted in a number of
      hypotheses on their origin and function. Calcareous corpuscles are believed to
      form either intracellularly or extracellularly and the cell type involved, the
      place of formation and the mechanism of mineral deposition seem to be also
      diverse. This review intends to provide an updated guide to the published
      literature on calcareous corpuscles in cestodes, giving emphasis on their role in
      larval physiology. Understanding biomineralization might lead to novel ways for
      the treatment of diseases caused by cestode larvae.

PMID- 10932771
TI  - [Cell cultures as a system for distinguishing between strains ofClostridium
      chauvoei and Clostridium septicum isolated in northeastern Mexico].
AB  - Clostridium chauvoei and C. septicum have similar characteristics as far as
      results from biochemical methods and gas chromatography (GC) are concerned. A
      total of 267 samples collected from sick or dead animals in the fields from
      Northeast Mexico, were bacteriologically analysed and differentiated by the GC
      technique. From these strains, 16 belong to the group of C. chauvoei/C. septicum.
      Studies on the effect of toxin on cell cultures of the lines EBL, 3T3, BHK21
      BSR/PK5/88, CHO-K1 and MDCK were performed. The objective was to obtain further
      data for identification, as the results from GC do not allow exact
      differentiation between C. chauvoei and C. septicum species. The results were
      obtained in tests with BHK21-BSR/PK5/88 cells as this had proved to be the most
      sensitive cell line, closely followed by 3T3 and CHO-K1 cells. MDCK cells were of
      little sensitivity. Results of the cytotoxin test of the 16 strains were
      reproducible and suggested a differentiation between C. chauvoei and C. septicum
      other than indicated by GC. The cytotoxin test is a highly specific system that
      provides also an additional method to distinguish between C. chauvoei and C.
      septicum strains.

PMID- 10932774
TI  - Diet-drug dilemma.

PMID- 10932773
TI  - The sunny side of eggs.

PMID- 10932775
TI  - Fibroid face-off.

PMID- 10932776
TI  - COX-2 inhibitors and Celebrex: safe or suspect?

PMID- 10932777
TI  - From sunburn to skin cancer.

PMID- 10932778
TI  - Low vitamin D linked to bone fractures.

PMID- 10932779
TI  - Gallbladder surgery: getting a better look.

PMID- 10932780
TI  - Drink fluids to lower cancer risk.

PMID- 10932782
TI  - More vitamin C recommended.

PMID- 10932781
TI  - Controlling acid reflux disease.

PMID- 10932783
TI  - Do aneurysms run in your family?

PMID- 10932784
TI  - Driving safely with epilepsy.

PMID- 10932785
TI  - The development of reference materials for paralytic shellfish poisoning toxins
      in lyophilized mussel. I: Interlaboratory studies of methods of analysis.
AB  - This paper describes the first part of a project undertaken to develop mussel
      reference materials for Paralytic Shellfish Poisoning (PSP) toxins. Two
      interlaboratory studies were undertaken to investigate the performance of the
      analytical methodology for several PSP toxins, in particular saxitoxin (STX) and
      decarbamoyl-saxitoxin (dc-STX) in lyophilized mussels, and to set criteria for
      the acceptance of results to be applied during the second part of the project:
      the certification exercise. In the first study, 18 laboratories were asked to
      measure STX and dc-STX in rehydrated lyophilized mussel material and to identify
      as many other PSP toxins as possible with a method of their choice. In the second
      interlaboratory study, 15 laboratories were additionally asked to determine
      quantitatively STX and dc-STX in rehydrated lyophilized mussel and in a saxitoxin
      enriched mussel material. The first study revealed that three out of four post
      column derivatization methods and one pre-column derivatization method sufficed
      in principle to determine STX and dc-STX. Most participants (13 of 18) obtained
      acceptable calibration curves and recoveries. Saxitoxin was hardly detected in
      the rehydrated lyophilized mussels and results obtained for dc-STX yielded a CV
      of 58% at a mass fraction of 1.86 mg/kg. Most participants (14 out of 18)
      identified gonyautoxin-5 (GTX-5) in a hydrolysed extract provided. The first
      study led to provisional criteria for linearity, recovery and separation. The
      second study revealed that 6 out of 15 laboratories were able to meet these
      criteria. Results obtained for dc-STX yielded a CV of 19% at a mass fraction of
      3.49 mg/kg. Results obtained for STX in the saxitoxin-enriched material yielded a
      CV of 19% at a mass fraction of 0.34 mg/kg. Saxitoxin could not be detected in
      the PSP-positive material. Hydrolysis was useful to confirm the identity of GTX-5
      and provided indicative information about C1 and C2 toxins in the PSP-positive
      material. The methods used in the second interlaboratory study showed
      sufficiently consistent analysis results to undertake a certification exercise to
      assign certified values for STX and dc-STX in lyophilized mussel.

PMID- 10932786
TI  - Influence of atmospheric pollution on the lead content of wines.
AB  - Over the last century, the atmospheric fallout of anthropogenic lead has evolved
      with time, as a function of the chronological variability of transient lead
      inputs from both industrial and gasoline origins. This variability has been
      mostly documented over North America and northern Europe. In this study we used
      ICP-MS for the determination of lead isotope ratios and showed that a series of
      French wines followed the evolution of the environmental lead record over the
      last century. We observe the same three-step chronological evolution of the lead
      isotopic composition, which reflects a western European signal. In the post 1950
      vintages, the lead isotope composition reflects a dominant atmospheric fallout.
      Since approximately 1950, Pb concentrations have been much lower than before,
      decreasing consistently from approximately 0.25 mg l-1 around the early 1950s,
      down to less than approximately 0.1 mg l-1 nowadays. Reflecting the airborne
      pollution, the lead isotopic signature is also specific of the continental origin
      of the wines and lead isotope ratios determination in wines appears to be a
      promising tool for certifying wine authenticity.

PMID- 10932787
TI  - Toxic and trace elements in liver, kidney and meat from cattle slaughtered in
      Galicia (NW Spain).
AB  - The aims of this study were to determine the levels of some toxic and trace
      metals in cattle meat in Spain and to compare them with concentrations in cattle
      elsewhere and to maximum acceptable levels. Arsenic, cadmium, lead, copper and
      zinc concentrations in the liver, kidney and muscle (meat) from 438 calves (6-10
      months old) and 56 cows (2-16 years old) slaughtered in Galicia (NW Spain) in
      1996 were quantified. The arithmetic mean fresh weight concentrations in calf
      liver, kidney and muscle respectively were 0.043, 0.055, 0.004 mg/kg for arsenic,
      0.032, 0.070, 0.001 mg/kg for cadmium, 0.053, 0.052, 0.009 mg/kg for lead, 64.6,
      4.91, 0.677 mg/kg for copper and 47.7, 14.4, 47.8 mg/kg for zinc. In cows, these
      concentrations were 0.046, 0.068, 0.005 mg/kg (arsenic), 0.097, 0.458, 0.001
      mg/kg (cadmium), 0.057, 0.066, 0.017 mg/kg (lead), 60.3, 3.67, 1.26 mg/kg
      (copper) and 59.8, 20.0, 52.7 mg/kg (zinc). Except for copper levels in the liver
      which were high, metal concentrations in cattle were generally low in Galicia and
      broadly similar to those in the rest of Europe, Australia and Canada. Arsenic,
      cadmium and lead concentrations in Galician cattle rarely exceeded acceptable
      maximum concentrations that have been adopted by many countries. Copper and zinc
      concentrations in Galician cattle did exceed acceptable maximum concentrations
      but the frequency with which this occurred depended upon which acceptable maximum
      concentration was used; regulatory values differ markedly between countries.

PMID- 10932788
TI  - Aflatoxin B1 residues in eggs of laying hens fed a diet containing different
      levels of the mycotoxin.
AB  - The present study was carried out to evaluate the excretion of aflatoxin B1
      residues in eggs of young laying hens fed aflatoxin B1-contaminated rations for 8
      weeks. To this end, 96 twenty-week-old hens were randomly distributed into four
      experimental groups (24 birds per group) and given rations containing either 0
      (controls), 100 micrograms, 300 micrograms or 500 micrograms aflatoxin B1/kg
      feed. Egg aflatoxin B1 residues were determined by thin layer chromatography; two
      samples per treatment per week were used for analysis. Egg production and average
      egg weights were not affected (p < 0.05) in the groups receiving aflatoxin B1
      contaminated rations. Residues of aflatoxin B1 were detected only in the eggs of
      hens given 500 micrograms/kg feed, at levels that ranged from 0.05 to 0.16
      microgram/kg (average: 0.10 microgram/kg). The results indicate that the feed to
      eggs aflatoxin B1 transmission ratio was approximately 5000:1, emphasizing the
      importance of controlling aflatoxin levels in rations for laying hens.

PMID- 10932789
TI  - A method for determining fumonisin B1 in corn using immunoaffinity column clean
      up and thin layer chromatography/densitometry.
AB  - A method for determining fumonisin B1 (FB1) in corn was developed and the clean
      up optimized in order to give an extract suitable for one-dimensional thin layer
      chromatographic (TLC) analysis. FB1 was extracted with a solution of
      methanol:water (80:20, v/v), purified through an immunoaffinity column and
      separated on a C18 reversed phase TLC plate. The FB1 was visualized with 0.1
      mol/l sodium tetraborate, 0.40 mg/ml fluorescamine in acetonitrile and 0.01 mol/l
      boric acid:acetonitrile (2:3, v/v) for fluorescence detection, and quantified by
      densitometric analysis. Water, acetonitrile:water (1:1 v/v) and
      acetonitrile:water (4:1 v/v) were evaluated as TLC solvents for running both
      standards and samples together with derivatization procedures aimed at improving
      separation, resolution, sensitivity and linearity. The mean recovery for FB1 for
      spiked samples was found to be 85% and the linear equation of standard
      calibration curve by densitometric analysis gave an r2 value higher than 0.99.
      The maximum coefficient of variation for replicate analysis of spiked samples was
      19%. The absolute amount of FB1 standard detectable on a TLC plate was 2 ng,
      giving a detection limit for the method of 0.1 mg/kg. The method has been shown
      to be robust in the application of FB1 monitoring in corn (214 samples) collected
      in different regions of the country. FB1 was detected in 99% of these samples in
      the range of 0.2 to 6 mg/kg.

PMID- 10932790
TI  - Determination of ethyl carbamate in some fermented Korean foods and beverages.
AB  - Ethyl carbamate has been associated with cancer for several decades. It is mainly
      found in fermented foods and beverages. In view of the importance of fermented
      foods in the Korean diet and the significant level of ethyl carbamate expected,
      we determined ethyl carbamate concentrations in some of the staple food items and
      estimated the daily intake for the Korean population. Ethyl carbamate in
      commercial samples of kimchi, soy sauce, vinegar, soybean paste, and alcoholic
      beverages were determined by gas chromatography-mass spectrometry/selective ion
      monitoring (GC-MS/SIM). Homemade soy sauce and kimchi were also analysed. The
      maximum ethyl carbamate concentrations observed were 73 micrograms/kg in soy
      sauce, 7.9 micrograms/kg in soybean paste, 2.5 micrograms/l in vinegar, 16.2
      micrograms/kg in kimchi and 15.4 mu/l in Korean traditional alcoholic beverages.
      Combining these values with the average daily food intake data, we estimated that
      the maximum daily exposure of Korean population to ethyl carbamate is 2.8
      micrograms/day, which is not a negligible amount considering the 'virtually safe
      dose' derived by animal experiment ranges between 1.2 and 4.8 micrograms/day. It
      would be desirable to closely monitor ethyl carbamate levels in Korean foods and
      to find ways to reduce the daily intake.

PMID- 10932791
TI  - Flashbulb memories? The effects of when the initial memory report was obtained.
AB  - Why have some researchers found reports of flashbulb memories to be stable, while
      others have observed inconsistencies? Paradoxically, it appears that relatively
      long delays between event and initial documentation have produced greater
      consistency of participants' reports. To investigate this directly, we collected
      the initial documentation of hearing about O.J. Simpson's acquittal either five
      hours or one week after the acquittal was read. Observed consistency of memories
      varied as a function of documentation time; following an eight-week retention,
      the delayed reports were more consistent. The delayed group also reported fewer
      propositions in their initial documentation. We proposed a consolidation model to
      explain these results: during the days immediately following a newsworthy event,
      the narrative structure of these memories changes in that some details are
      forgotten. After this consolidation period, the memories may solidify. Thus, it
      may have been easier for the delayed group to provide consistent memories at the
      two intervals.

PMID- 10932792
TI  - Interruption and bizarreness effects in the recall of script-based text.
AB  - Recall of script, script-irrelevant, and script-interruptive actions in script
      based stories was examined in four experiments. By varying the plausibility of
      the script-irrelevant and the script-interruptive actions, the bizarreness effect
      (i.e., enhanced recall for bizarre, implausible actions) was assessed within the
      context of script-based text. In addition, presentation of script-interruptive
      actions actions allowed for an assessment of the interruption effect (i.e.,
      enhanced recall for interruptive actions). A bizarreness effect was found, to the
      extent that implausible script-irrelevant actions were better recalled than their
      more plausible counterparts and script actions. However, implausible actions were
      not better recalled than script-interruptive actions, nor did bizarreness
      significantly enhance recall of script-interruptive actions. These results are
      discussed in terms of recent assumptions underlying interruptions underlying
      interruption and bizarreness effects, and in terms of recent assumptions about
      how scripted and nonscripted actions are retained in memory.

PMID- 10932793
TI  - Practice and feedback effects on the confidence-accuracy relation in eyewitness
      memory.
AB  - It has been claimed that the lack of a reliable confidence-accuracy relation in
      eyewitness memory stems from eyewitnesses' lack of knowledge concerning their
      relative expertise. Two studies tested this idea by contrasting the effects of
      practice alone with practice with feedback in three successive eyewitness tests.
      Experiment 1 tested recall for events, and Experiment 2 used recognition of faces
      as test materials. Both studies showed that practice alone did not increase the
      confidence-accuracy relation, but practice with feedback on relative performance
      produced robust increases in the confidence-accuracy relation. This suggests that
      lack of calibration is one factor that causes the reported lack of association
      between confidence and accuracy for eyewitness memory.

PMID- 10932794
TI  - A jigsaw puzzle theory of memory.
AB  - The principal novel feature of this paper is the notion that a coherent memory
      can be synthesised from a set of partially coherent memory fragments by
      maximising a particular function, Harmony (Smolensky, 1986). The appeal of
      Harmony is that it fulfils two functions: it is at the heart of the synthesis
      algorithm and it provides a natural measure for "feeling-of-knowing". The model
      is applied to feeling-of-knowing data, flashbulb memories, flashbacks,
      repression, dissociation, memory stability across repeated recalls, and the
      effects of cue size on retrieval.

PMID- 10932795
TI  - The distribution of early childhood memories.
AB  - The quantitative distribution of autobiographical memories for the first decade
      of life is described. The distribution, based on over 11,000 autobiographical
      memories from age 10 and younger from published studies, is nearly identical for
      males and females, for participants of different ages, and for different methods
      of collecting data, including using words to cue memories from anywhere in the
      lifespan or from just the childhood years, exhaustive listing of all early
      memories, and interviews.

PMID- 10932796
TI  - Assessment of chest pain in the emergency room. The role of nuclear cardiology.

PMID- 10932797
TI  - Mitochondrial oligomycin-sensitive ATPase during isoproterenol-induced cell
      injury of myocardium.
AB  - The enzymatic activity of the mitochondrial oligomycin-sensitive ATPase was
      investigated during isoproterenol-induced cell injury of myocardium, using rat
      heart homogenates and a potentiometric method. The enzymatic activity of the
      oligomycin-sensitive ATPase and the inhibitory action of oligomycin do not show
      significant alterations upon treatment with isoproterenol. These results are
      inconsistent with the hypothesis that modifications in the active configuration
      of the mitochondrial ATPase take place during isoproterenol-induced injury of
      myocardium.

PMID- 10932798
TI  - [Double inlet left ventricle. Morphopathology and surgical anatomy].
AB  - Because of the possibility of surgical treatment of double inlet left ventricle,
      its basic morphologic features of surgical and imaging importance are analyzed.
      Seventeen hearts were studied with the segmental sequential system. The situs was
      solitus in thirteen; dextroisomerism in three and levoisomerism in one. The
      atrioventricular valves were separated in nine; there was a common
      atrioventricular valve in eight; straddling of the atrioventricular valve in
      seven and stenosis in two. The rudimentary right ventricle was to the right side
      in twelve hearts and to the left side in five. The discordant ventriculoarterial
      connection was the most frequent (seven), followed by the concordant one (five)
      and double outlet right ventricle (five). There was pulmonary stenosis in five.
      The ventricular septum did not reach the crux cordis. The ventricular septal
      defect was bigger in straddling atrioventricular valves than in valves completely
      open into the left ventricle, being restrictive in ventriculoarterial
      concordance. Surgical treatment varies as the complexity of this cardiopathy
      does, from cardiac septation to palliation procedures. The morphologic knowledge
      of this cardiac malformation is basic to interpret correctly the diagnostic
      imaging.

PMID- 10932799
TI  - [Chromosome 22 (22q.11.2) deletion. Etiology of conotruncal heart abnormalities].
AB  - Important advances in the diagnosis and treatment of congenital heart disease
      (CHD) have been made in the past 50 years. Nowadays echocardiogram plays an
      important role in the diagnosis. This procedure is able to identify a wide range
      of malformations. Cardiac catheterization is mainly a therapeutic tool, surgery
      is now performed much earlier because CHDS are diagnosed sometimes before birth
      or very early in life. All this advances in the diagnosis and treatment of this
      group of patients, allows them not only a better quality of life but also the
      possibility of reaching adulthood and having children. The study of the etiology
      of CHD is a field that has not evolved as fast as the assessment and treatment.
      Nowadays we have a larger population of adults with CHD. The discovery of a
      microdeletion of chromosome 22 q11.2 associated with conotruncal cardiac defects,
      proves a common etiology for clinical phenotypes and conotruncal malformations.
      In order to identify, which of these patients share the same etiology and
      presented with this syndrome, we collected a group that shared not only heart
      defects of the conotruncal type but also specific phenotypic alterations such as
      broad nasal bridge, nasal dimple, high palate, and digitalization of the first
      finger among others. The first two patients studied with FISH technique were
      positive to monosomy of a locus on chromosome 22. Those patients with CHD of
      conotruncal type should undergo microdeletion testing so genetic counseling can
      be offered as well as appropriate treatment in areas such as cardiology and
      developmental psychology.

PMID- 10932800
TI  - [Initial experience with the use of Levovist in adult patients with suboptimal
      echocardiograms].
AB  - OBJECTIVE: To report our experience with the use of Levovist in echocardiographic
      studies. METHOD: We studied consecutively patients with suboptimal
      echocardiographic studies. A bolus of 4 gr @ 400 mg/ml was administered via
      antecubital vein and a second echocardiogram was performed during the ensuing
      minutes. RESULTS: Between June and July 1998 we studied 16 patients with
      suboptimal echocardiograms, seven males and nine females, ages 29-77. There were
      six patients with coronary artery disease (CAD), three with mitral regurgitation
      (MR), one with dynamic subaortic stenosis, five with right chambers dilatation
      and one with a left atrial tumor. No patient referred discomfort or had any
      complication-with Levovist. The mean time of the contrast effect was nine
      minutes. A better delineation of endocardial borders was observed this allowed
      better evaluation of wall motion and left ventricular function in patients with
      CAD. There was Doppler enhancement in patients with MR and subaortic stenosis
      facilitating its evaluation. We documented atrial septal defect non visualized
      previously in two of five patients with right chambers dilatation. There was a
      better delineation of the left atrial tumor. CONCLUSIONS: Levovist showed
      enhancement of all Doppler modalities and facilitated de evaluation of MR, left
      ventricular function, subaortic stenosis and a cardiac tumor. It was safe and
      well tolerated.

PMID- 10932802
TI  - [A comparative study of Rashkind, Grifka and coil devices in percutaneous closing
      of patent ductus arteriosus].
AB  - This study was performed to evaluate the efficacy of transcatheter Coil and
      Grifka closure of the patent ductus arteriosus in comparison to our experience
      with the Rashkind umbrella device. Ninety seven patients (36 male and 61 females)
      underwent occlusion of the PDA. The following variables were compared: age, sex,
      ductus diameter, morphology, device, occlusion time, residual shunt, multiple
      device and complications. Data obtained were compared using the Student's test
      and Chi 2. Median patient age was 7.82 +/- 6.89, forty five patients underwent
      transcatheter Rashkind-17 closure, 19 patients with Rashkind-12, 18 patients with
      Coil and 13 patients with Grifka device, in two patients the closure could not be
      performed. There were differences between the morphology and device used (p =
      0.008), between the ductus diameter and device used (p < 0.001). There was
      immediate closure in 26.7% in the Rashkind-17 group compared with, 57.9% for the
      Rashkind-12 group, 83.3% for Coil group and of 91.7% for Grifka group. The
      occlusion within 24 hrs of implantation was 60% with Rashkind-17, 78.9% with
      Rashkind-12, 94.4% with Coil and 100% with Grifka. Residual shunt persisted for
      more than a year in 7 patients with Rashkind-17 and 1 with Rashkind 12, (p =
      0.001), in 4 patients two devices wore placed. The complications were, 15.5% for
      Rashkind-17, 26.3% for Rashkind-12, 5.2% for Coil and 30% for Grifka, (p =
      0.004), one coil and one Grifka embolized. Transcatheter Coil and Grifka
      occlusion are more effective in achieving immediate closure than the Rashkind
      device. The indication to use each device is made according to the morphology and
      size of the ductus.

PMID- 10932801
TI  - [Pharmacological cardioversion with intravenous propafenone in atrial
      fibrillation].
AB  - The efficacy and safety of intravenous propafenone for conversion of recent-onset
      and chronic atrial fibrillation was assessed in 46 patients. 40 with atrial
      fibrillation associated with or without structural heart disease (mean age 63 +/-
      14 years) and 6 patients with atrial fibrillation related to the Wolff-Parkinson
      White syndrome (mean age 34.8 +/- 13 years). Propafenone treatment was
      administered at 2 mg/kg over 15 minutes under continuous electrocardiographic
      monitoring. In 28 of 32 (87.5%) patients with paroxysmal and/or recent-onset
      atrial fibrillation a stable sinus rhythm was restored within 1 hour after
      propafenone (mean 17 +/- 11 minutes) and in only 3 of 8 (37.5%) with chronic
      atrial fibrillation (p < 0.05). Conversion to sinus rhythm was obtained in 5 of 6
      (83.3%) patients with atrial fibrillation related ventricular preexcitation, mean
      time 21 +/- 12 minutes. Propafenone had an additional effect reducing mean heart
      rate (141 +/- 21 to 102 +/- 15 beat per minute, p < 0.05) and the shortest
      preexcited R-R intervals was increased, mean 231.6 +/- 27.8 to 355 +/- 37.2
      milliseconds (p < 0.001) in cases associated with ventricular preexcitation.
      Dizziness, hypotension and transient conduction disturbances occurred in only one
      patient with rheumatic valvular heart disease: EF 40%. Propafenone is an
      effective and safe antiarrhythmic drug for converting paroxysmal and/or recent
      onset atrial fibrillation of various origins with a more limited efficacy in
      chronic atrial fibrillation.

PMID- 10932803
TI  - [Focal atrial fibrillation treated with radiofrequency].
AB  - Atrial fibrillation is usually thought to be due to multiple circulating
      reentrant wavelets. From previous studies, a focal mechanism is considered to be
      very unlikely. This focal source could be successfully treated by radiofrequency
      catheter ablation. We report a patient without structural heart disease, but with
      multiple episodes of syncope and palpitations related to atrial tachycardia and
      atrial fibrillation. Electrophysiological study demonstrated that all atrial
      arrhythmias were due to one focus located in the left atrium at the ostium of the
      left superior pulmonary vein that was successfully treated with the use of a mean
      of three radiofrequency pulses, without complications. The pulmonary veins are an
      important source of ectopic beats, initiating frequent paroxysm of atrial
      fibrillation. These foci respond to treatment with radiofrequency ablation.

PMID- 10932804
TI  - [Placement of permanent epicardial pacemaker in a newborn with congenital
      complete AV block].
AB  - Isolated congenital atrioventricular block is reported in one out of 20,000 live
      births. The optimistic view on the prognosis and indications for permanent pacing
      have been modified in the last 35 years. The purpose of this report is to present
      a prenatally diagnosed case, outlining the surgical technique for permanent
      pacing. The infant was a male born by cesarean section, weighted 3030 grs and had
      a structurally normal heart. His ECG showed complete AV block with narrow QRS,
      atrial rate was 140 and ventricular rate was 55. We implanted a epicardial
      pacemaker VVIR by midline laparatomy. The lead was unipolar 35 cms long screw-in
      type and was placed in the right ventricle through the xiphoid process. The
      pacemaker was placed in a GoreTex bag and fixed intraperitoneal to the abdominal
      wall. The infant did well after the procedure and he was discharged in good
      condition one week later. We conclude that it is appropriate to implant a
      permanent pacemaker in these patients with low ventricular rate thus reducing the
      risk of sudden cardiac death. The surgical technique is safe and makes easy the
      generator replacement.

PMID- 10932805
TI  - [Thoracic circle in the electrical exploration of the heart].

PMID- 10932807
TI  - Drug use and abuse in sport.
AB  - This chapter describes evolving patterns of drug misuse in sport, and reciprocal
      systems for defining and detecting doping, across the late twentieth century. The
      International Olympic Committee's list of prohibited substances and methods is
      presented as a primary tool for developing and administering such systems.
      Developments in the list since its introduction have been stimulated both by
      increasingly sophisticated detection methods, and by the imperative to recognise
      and anticipate trends in doping. The historical argument that doping is
      incompatible with the ethical nature of sport, and relates to pressures and
      inducements to misuse drugs, particularly at the elite level, is also addressed.
      Finally, recent developments in international collaboration between governments
      and the sporting community are covered, and continued efforts to harmonize
      standards in anti-doping policies and practices are advocated.

PMID- 10932808
TI  - Doping among adolescent athletes.
AB  - The use of drugs to enhance physical performance and appearance has been observed
      for thousands of years. Today individuals, including adolescents, continue to
      employ a wide variety of drugs in the hope of improving their athletic
      performance and looking better. Unfortunately, beyond the assessment of anabolic
      androgenic steroid (AAS) use, very little is known regarding the use, safety and
      efficacy of other performance-enhancing drugs and nutritional supplements among
      adolescents. Most studies report that 3-12% of adolescent males admit to using an
      AAS at some time during their life. Among adolescent females, studies find that 1
      2% report having used steroids. The current strategy for dealing with performance
      enhancing drug use by adolescents is multi-faceted and primarily involves
      education and prevention strategies, interdiction and drug testing programmes.
      However, the demand for performance-enhancing drugs has been created by our
      societal fixation on winning and physical appearance. In order to alter the
      current use of performance-enhancing drugs by adolescents, we as a society must
      come to grips with our addiction to sport and the importance we place on winning
      and appearance. We must change our values.

PMID- 10932806
TI  - [Release of nitric oxide induced by blood flow. Update and perspectives of
      research].

PMID- 10932809
TI  - The female athlete.
AB  - Over the past 30 years, the number of women participating in organized sports has
      grown dramatically. Several forms of menstrual irregularities have been described
      in the female athlete: primary and secondary amenorrhoea, oligomenorrhoea, short
      luteal phases and anovulation. The incidence of menstrual irregularities is much
      higher in activities where a thin body is required for better performance. The
      hormonal pattern seen in these athletes is a hypothalamic amenorrhoea profile.
      There appears to be a decrease in gonadotrophin-releasing hormone (GnRH) pulses
      from the hypothalamus, which in turn decreases the pulsatile secretion of
      luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and shuts down
      stimulation of ovary. Recently, another type of amenorrhoea has been described in
      swimmers which is characterized by mild hyperandrogenism. Athletes with low
      weight are at risk of developing the female athletic triad, which includes
      amenorrhoea, osteoporosis and disordered eating. Athletes with this triad are
      susceptible to stress fractures. Other issues include the pregnant athlete.
      Intensive exercise during pregnancy can cause bradycardia. Safe limits of aerobic
      exercise in pregnancy depend on previous exercise habits. Infertility, which may
      develop with exercise, is probably reversible with reduction of exercise or
      weight gain. High impact sports activities may produce urinary incontinence.
      Oestrogen replacement therapy is often prescribed in amenorrhoeic athletes, but
      bone loss may not be completely reversible.

PMID- 10932810
TI  - Anabolic steroids.
AB  - Anabolic steroids are synthetic derivatives of testosterone modified to enhance
      the anabolic rather than the androgenic actions of the hormone. The anabolic
      effects are considered to be those promoting protein synthesis, muscle growth and
      crythopoiesis. There are numerous side-effects to anabolic steroids, including
      hypertension and atherosclerosis, blood clotting, jaundice, hepatic carcinoma,
      tendon damage, psychiatric and behavioural effects and, in males, reduced
      fertility and gynaccomastia. Anabolic steroids were added to the International
      Olympic Committee's list of banned substances in 1975. The majority of 'evidence'
      concerning the efficacy of anabolic steroids as performance enhancing agents is
      anecdotal. In the main, experimental investigations have been poorly designed
      scientifically, clinically and statistically. The percentage of positive test
      results from IOC accredited laboratories has remained consistently low. However,
      athletes take their steroids during training and out-of-competition testing is
      not conducted in all countries, although international co-operation is now under
      consideration. Despite the lack of conclusive evidence, steroids users will
      continue to hold the view that their effects are efficacious and they are
      therefore unlikely to be persuaded to curtail their use.

PMID- 10932811
TI  - Growth hormone abuse.
AB  - Doping with growth hormone (GH) has become an increasing problem in sports during
      the last 10 years. GH has a reputation of being fairly effective among GH users,
      although the effectiveness is not undisputed, and the few controlled studies that
      have been performed with supraphysiological GH doses to athletes have shown no
      significant positive effects of GH in the aspect of a doping agent. There is no
      method yet to discover GH doping, but current intensive research in this matter
      will hopefully produce a method in the years to come. This article describes the
      GH physiology, the clinical use of GH, the athlete's view, administration
      regimens and side effects.

PMID- 10932812
TI  - Central nervous system stimulants.
AB  - Three major types of CNS stimulant are currently abused in sport: amphetamine,
      cocaine and caffeine. Each drug type has its own characteristic mechanism of
      action on CNS neurones and their associated receptors and nerve terminals.
      Amphetamine is widely abused in sports requiring intense anaerobic exercise where
      it prolongs the tolerance to anaerobic metabolism. It is addictive, and chronic
      abuse causes marked behavioural change and sometimes psychosis. Major sports
      abusing amphetamine are cycling, American football, ice-hockey and baseball.
      Cocaine increases tolerance to intense exercise, yet most of its chronic effects
      on energy metabolism are negative. Its greatest effects seem to be as a central
      stimulant and the enhancement of short-term anaerobic exercise. It is highly
      addictive and can cause cerebral and cardiovascular fatalities. Caffeine enhances
      fatty acid metabolism leading to glucose conservation, which appears to benefit
      long-distance endurance events such as skiing. Caffeine is also addictive, and
      chronic abuse can lead to cardiac damage. Social abuse of each of the three drugs
      is often difficult to distinguish from their abuse in sport.

PMID- 10932813
TI  - Blood boosting and sport.
AB  - Reinfusion of whole blood or packed red blood cells (RBCs) increasing the
      haemoglobin concentration ([Hb]) above the individual's normal values increases
      VO2max and enhances physical performance. During submaximal exercise heart rate
      and blood lactate concentration ([Hla]) are reduced, while arterial blood
      pressure remains unchanged despite increased haematocrit (Hct). There is no
      method available for detecting this type of blood 'doping'. Seven weeks of
      injection with recombinant human erythropoietin (rhEPO) (20-40 IU per kg body
      weight) increased [Hb] and Hct, maximal oxygen uptake (VO2max) and physical
      performance were increased. The change in VO2max per gram change in [Hb] is the
      same after reinfusion of blood and after rhEPO injections. During submaximal
      exercise arterial blood pressure is increased, which despite a reduced heart
      rate, puts greater stress on the circulation even in trained athletes. An
      electrophoretic method is available to detect the use of rhEPO but it is costly
      and slow and therefore it can not be used in sport. Indirect markers of increased
      erythopoiesis may be used. However, further research in this field is necessary.

PMID- 10932814
TI  - Test method: GH.
AB  - The abuse of recombinant human growth hormone in sports is considered to be a
      widespread phenomenon, but until today all our knowledge thereof is based on
      rumor, anonymous surveys or accidental observations by customs officers. Although
      growth hormone (GH) is listed as a prohibited class E substance by the
      International Olympic Committee (IOC) no official test for the detection of GH
      abuse is implemented. Because of the high degree of identity in the amino acid
      sequence between recombinant and endogenous GH and because of the pulsatile
      nature of GH secretion, as well as inter-individual variations, it was believed
      to be undetectable. Recently, new proposals have been made to overcome this
      problem. On the basis of differential immunoassays it is possible to determine
      the relative content of GH isoforms in the circulation and thus to detect the
      application of recombinant GH. Furthermore, changes in GH dependent parameters
      after the administration of recombinant GH have been shown to be a possible
      indicator of GH abuse.

PMID- 10932815
TI  - Test methods: anabolics.
AB  - In the International Olympic Committee (IOC) accredited laboratories, specific
      methods have been developed to detect anabolic steroids in athletes' urine. The
      technique of choice to achieve this is gas-chromatography coupled with mass
      spectrometry (GC-MS). In order to improve the efficiency of anti-doping
      programmes, the laboratories have defined new analytical strategies. The final
      sensitivity of the analytical procedure can be improved by choosing new
      technologies for use in detection, such as tandem mass spectrometry (MS-MS) or
      high resolution mass spectrometry (HRMS). A better sample preparation using
      immuno-affinity chromatography (IAC) is also a good tool for improving
      sensitivity. These techniques are suitable for the detection of synthetic
      anabolic steroids whose structure is not found naturally in the human body. The
      more and more evident use, on a large scale, of substances chemically similar to
      the endogenous steroids obliges both the laboratory and the sports authorities to
      use the steroid profile of the athlete in comparison with reference ranges from a
      population or with intraindividual reference values.

PMID- 10932816
TI  - Erythropoietin test methods.
AB  - Recombinant human erythropoietin (rhEPO), which increases red cell mass, is one
      of the most abused substances in sport. Abuse is currently undetectable by the
      only direct routine method, immunoassay, since blood and urine rhEPO are
      immunologically indistinguishable from endogenous EPO. Elevated EPO levels are
      only detectable several days after rhEPO administration. Indirect parameters have
      therefore been introduced, primarily the haematocrit level, but also markers of
      functional iron deficiency during or after rhEPO administration (hypochromic red
      cells and reticulocytes, serum transferrin receptors, ferritin levels) and, in
      the urine, fibrin degradation products. Although iron status indices have yielded
      promising results, athletes are currently banned solely on the basis of their
      haematocrit. Yet various factors can cause false positive haematocrit results
      with potentially fatal consequences to athletes' careers. Until new direct assays
      such as liquid chromatography-mass spectrometry have been evaluated and
      introduced, efforts must be directed at using a battery of tests to increase the
      sensitivity and specificity and reduce the number of false positives and false
      negatives.

PMID- 10932818
TI  - Ionizing radiation, part 1: X- and gamma-radiation, and neutrons. Overall
      introduction.

PMID- 10932817
TI  - Techniques for analytical testing of unconventional samples.
AB  - Forensic scientists have long detected the presence of drugs and their
      metabolites in biological materials using body fluids such as urine, blood and/or
      other biological liquids or tissues. For doping analysis, only urine has so far
      been collected. In recent years, remarkable advances in sensitive analytical
      techniques have encouraged the analysis of drugs in unconventional biological
      samples such as hair, saliva and sweat. These samples are easily collected,
      although drug levels are often lower than the corresponding levels in urine or
      blood. This chapter reviews recent studies in the detection of doping agents in
      hair, saliva and sweat. Sampling, analytical procedures and interpretation of the
      results are discussed in comparison with those obtained from urine and blood
      samples.

PMID- 10932819
TI  - X-radiation and gamma-radiation.

PMID- 10932820
TI  - Neutrons.

PMID- 10932821
TI  - Physiology of pain.
AB  - The substantial increase in our collective knowledge of pain physiology and
      pharmacology over the past decade has had a significant effect on the practice of
      clinical veterinary medicine. An overview of the basic anatomical and physiologic
      components of nociceptive processing is presented, as well as a discussion of the
      sensitizing events that occur within the nervous system in acute and chronic
      pathologic pain states. The unique features of visceral and neuropathic pain are
      also outlined. With the goal of improving the success of our therapeutic
      interventions, the final section is devoted to the various classes of analgesic
      drugs and techniques, and how they are best incorporated into pain management
      strategies.

PMID- 10932822
TI  - Pain assessment and general approach to management.
AB  - To manage pain successfully, assessment of the presence and degree of pain is
      essential. This article describes the various signs and behaviors that may be
      presumed to be associated with pain of varying degrees. Conditions that are
      associated with pain and situations that influence the severity of pain are also
      discussed. The general approach to management of these situations is outlined,
      with an introduction to the various articles in this issue dealing with specific
      mechanisms and modalities involved in the treatment of pain.

PMID- 10932823
TI  - Opioid analgesics.
AB  - Opioids are useful and potent drugs for the management of pain in small animal
      patients. They have a wide therapeutic index and can be given by a number of
      different routes. Some of these techniques (e.g., epidural and intraarticular)
      allow for the production of profound analgesia in a localized area of the body
      while limiting the dose and the side effects, and others provide a noninvasive
      method for the delivery of continuous analgesia (e.g., transdermal
      administration).

PMID- 10932824
TI  - Mechanism of action of nonsteroidal anti-inflammatory drugs.
AB  - After more than a century of use, pharmacologists thought they had discovered the
      mechanism of action of nonsteroidal anti-inflammatory drugs (NSAIDs) when their
      inhibitory action on the production of prostaglandins was described. This action
      was located at the inhibition of the enzyme responsible for the conversion of
      arachidonic acid to prostaglandins, namely cyclo-oxygenase. More recently, it has
      been recognized that more than one isoform of the enzyme exists. The two forms of
      cyclo-oxygenase described are widely different in their location, activity, and
      role, especially because the COX-1 isoenzyme seems to be mainly a constitutive
      enzyme whereas the COX-2 isoenzyme is inducible. This separation of activity
      appears to be correlated with the separation of function of the various
      prostaglandins, whereas the constitutive form is associated with "physiologic"
      functions and the inducible form with inflammatory responses. Recent advances
      have included the development of drugs with a high specificity toward the
      inducible enzyme (COX-2) to focus on the anti-inflammatory actions, because many
      of the unwanted side effects of NSAIDs have been associated with inhibition of
      the constitutive isoform (COX-1). Other recent developments in studies of the
      NSAIDs have included potential therapeutic actions in other degenerative
      conditions.

PMID- 10932825
TI  - Nonsteroidal anti-inflammatory analgesics. Indications and contraindications for
      pain management in dogs and cats.
AB  - Nonsteroidal anti-inflammatory analgesics (NSAIAs) are effective in controlling
      most acute and chronic pain conditions. In veterinary practice these analgesics
      may be superior to opioids in that the duration of action is much longer, with
      equal efficacy in many instances, making effective pain management possible for
      most veterinary patients. NSAIAs act synergistically in combination with other
      modalities of pain management, including all opioids, local anesthetics, and
      various sedatives. Because of their mechanism of action, however, there is a
      potential for perturbation of several homeostatic functions mediated by
      prostaglandins. Not all NSAIAs are equal in efficacy and safety, so careful
      patient and NSAIA selection with appropriate monitoring is advised. This article
      discusses the indications and contraindications for NSAIA use with a short
      description of the currently available NSAIAs approved for use in veterinary
      patients.

PMID- 10932826
TI  - Adjunctive analgesic therapy.
AB  - Adjuvant analgesics are drugs that have weak or nonexistent analgesic action when
      administered alone but can enhance analgesic actions when coadministered with
      known analgesic agents. Such agents are often administered in cases of refractory
      pain. For some chronic pain syndromes, however, they may constitute a first-line
      approach. Because pain is such an individual experience, analgesic regimens may
      require several drugs at varying dosages to confer a comfortable state.
      Adjunctive therapies such as the tricyclic antidepressants, anticonvulsants, N
      methyl-D-aspartic acid receptor antagonists and low-dose intravenous local
      anesthetics, to name a few, have proved to be efficacious in relieving certain
      types of pain, especially neuropathic and cancer pain. Their use in animals is
      increasing, with anecdotal reports of some success.

PMID- 10932827
TI  - Pharmacologic considerations for opiate analgesic and nonsteroidal anti
      inflammatory drugs.
AB  - When administering opioid analgesic drugs or nonsteroidal anti-inflammatory
      drugs, veterinarians are often not familiar enough with the underlying
      pharmacology of the drugs, particularly with the potential for drug interactions
      and adverse effects. This article considers some of the pharmacologic features of
      these drugs and provides a basis for important interactions, contraindications,
      and adverse effects.

PMID- 10932828
TI  - Local and regional anesthesia.
AB  - Local anesthetics have the unique ability to produce complete blockade of sensory
      nerve fibers and prevent or pre-empt the development of secondary (central)
      sensitization to pain. For this reason, local and regional anesthetic techniques
      are often used with opioids, alpha 2-receptor agonists, dissociatives, and anti
      inflammatory drugs as part of a multimodal strategy to manage pain. Lidocaine and
      bupivacaine are the local anesthetics used most commonly in dogs and cats.
      Lidocaine has a fast onset (10-15 min) and an intermediate duration of action (60
      120 min), and is used for short diagnostic and surgical procedures. Bupivacaine
      has a slow onset (20-30 min) and a long duration of action (240-360 min), and is
      used to control pain both preoperatively and postoperatively. Local anesthetics
      are relatively safe if they are administered correctly. Administration of an
      excessive dose and accidental intravenous administration are probably the most
      common causes of systemic toxicity in small animals. Doses of local anesthetics,
      especially those for cats and small dogs, should always be calculated carefully.
      In many animals, the most simple and elegant way to control pain perioperatively
      is to perform a local or regional anesthetic block. Veterinarians should not
      hesitate to incorporate local and regional anesthetic techniques into their pain
      management strategies for dogs and cats.

PMID- 10932829
TI  - Epidural analgesia and anesthesia.
AB  - This review describes the beneficial effects of the use of epidural drugs for pre
      emptive analgesia, intraoperative analgesia with an inhalant-sparing effect, and
      prolonged postoperative analgesia. Epidural morphine oxymorphone, or
      hydromorphone is recommended for use in small animals in combination with a local
      anesthetic of appropriate duration for procedures involving the hind end,
      although epidural morphine or hydromorphone may be more appropriate for
      procedures on the thorax and forelimbs. Side effects are few and can usually be
      easily managed, with the benefits outweighing any detrimental effects that might
      occur.

PMID- 10932830
TI  - Acupuncture for management of pain.
AB  - Acupuncture is the technique of inserting needles into specific areas of the body
      to elicit a physiologic response. Although acupuncture is based on the paradigms
      of traditional Chinese medicine, there are numerous physiologic and clinical
      studies that document and validate its use. Control of pain is a major indication
      for the use of acupuncture. It can be used in conjunction with analgesic drugs or
      alone to make patients more comfortable.

PMID- 10932831
TI  - Chemical restraint and analgesia for diagnostic and emergency procedures.
AB  - Diagnostic or emergency procedures are a necessity; however, the accompanying
      stress, discomfort, and pain must be considered and alleviated. The requirement
      for restraint and analgesia varies with the individual animal and its condition.
      Safe protocols are suggested for specific patient concerns. Recommendations for
      stabilization are included to reduce the detrimental effects of the drugs used.
      Alternatives are presented when feasible for animals in less critical condition.
      Technique of administration and dose adjustment is covered, as is drug selection.

PMID- 10932832
TI  - Acute pain management.
AB  - We encounter patients with acute pain many times each day, and few aspects of
      veterinary practice offer such an opportunity to help so many in such a
      profoundly rewarding way. As emphasized here and elsewhere, we now have excellent
      tools with which to help these animals, and the biggest impediment to optimal
      treatment of their pain is often our own difficulty in recognizing its presence.
      Perhaps the single most important aspect of treating acute pain is to cultivate
      an ability to see past our personal biases and expectations which may limit
      treatment and to rediscover the common sense we had about pain before we entered
      the profession. By rededicating ourselves to seeking out, preventing, and
      relieving pain, we not only perform a vital service for our patients but also
      elevate our profession even as we reap financial and spiritual rewards for our
      efforts. What could be better?

PMID- 10932833
TI  - Perioperative pain management.
AB  - The management of perioperative pain starts with the use of approaches to
      minimize anxiety and distress before the procedure. The administration of
      analgesics or local anesthetics before the start of surgery reduces the
      nociceptive input occurring during the procedure and reduces the need for
      postoperative analgesics. As the animal recovers from anesthesia, it is important
      to administer analgesics to minimize the patient's experience of pain and to
      continue this therapy through at least the first 12 to 24 hours. Techniques that
      provide a continuous level of analgesia are more effective than those that allow
      the pain to return.

PMID- 10932834
TI  - Management of chronic osteoarthritic pain.
AB  - Osteoarthritis is a common cause of chronic pain in small animals. Although there
      is currently no known cure, the disease can often be palliated by a combination
      of weight control, regulated exercise, anti-inflammatory medications, and disease
      modifying osteoarthritic agents. The diagnosis, recommended treatments, and many
      of the newer drugs and disease-modifying agents are discussed in this article.

PMID- 10932835
TI  - Management of cancer pain.
AB  - Pain secondary to cancer in animals should be promptly addressed to alleviate
      suffering, stress, and anxiety and to improve quality of life. Uncontrolled
      cancer pain can have a negative effect on the owners and caregivers of affected
      animals. The pathophysiology of cancer pain is discussed in this article, along
      with pain evaluation and monitoring. Treatment of cancer pain should be
      individualized, and a step-wise approach to the management of cancer pain is
      presented. The use of opioids, nonsteroidal anti-inflammatory drugs, and adjuvant
      medications are also reviewed.

PMID- 10932836
TI  - Update: AIDS malignancies, AIDS prevention.

PMID- 10932837
TI  - HAART and adherence.

PMID- 10932839
TI  - Deja vu all over again?

PMID- 10932838
TI  - Fulminant liver failure from acute HCV superinfection in a patient with HIV, HBV,
      and HDV coinfections.

PMID- 10932840
TI  - Global network to advance development of HIV vaccines.

PMID- 10932841
TI  - Viral changes lead to chronic hepatitis C.

PMID- 10932842
TI  - Drug abuse, HIV/AIDS, and hepatitis C.

PMID- 10932843
TI  - Disulfiram and buprenorphine for treating cocaine addiction.

PMID- 10932844
TI  - New Web site provides information about the NIH Minority Health Initiative.

PMID- 10932845
TI  - Viability of HIV-1 in syringes: implications for interventions among injection
      drug users.
AB  - We have determined that the duration of survival of HIV-1 in syringes typically
      used by injectors of illicit drugs can exceed 6 weeks. The percentage of syringes
      with viable virus varied with the volume of blood remaining in the syringes and
      the temperature at which syringes were stored. These experiments underscore the
      need for needle exchange programs and other HIV prevention interventions that
      promote the availability of clean syringes and the removal of potentially
      infectious ones from circulation.

PMID- 10932846
TI  - Strategies to optimize the impact of needle exchange programs.
AB  - In the United States today, half of all new HIV infections are injection drug use
      associated, many of which are a result of the reuse and sharing of contaminated
      syringes. Thus, providing access to sterile syringes for injection drug users is
      an important part of preventing HIV transmission. Needle exchange programs (NEPs)
      have been established as one successful approach to providing sterile injection
      equipment. The medical literature shows that these programs are effective in
      decreasing both syringe sharing and HIV incidence in injection drug users. In
      addition, many NEPs are also beneficial because they provide other injection drug
      use-relevant services. There are several strategies that can be adopted in order
      to optimize the impact of needle exchange programs, at both the community and
      national levels. These include establishing NEPs in communities that need them,
      expanding and improving those that already exist, and implementing such programs
      on a larger national scale with the provision of federal funds.

PMID- 10932847
TI  - HIV among older adults: age-specific issues in prevention and treatment.
AB  - A substantial and increasing number of people have acquired HIV infections in
      their later years, as a result of male-to-male sexual contact or blood
      transfusion. However, heterosexual transmission also occurs, and substance abuse
      is often a factor. Health and service practitioners need to develop sensitivity
      to the needs of HIV-infected elderly people and their families. Prevention
      efforts and education should be incorporated as part of their initial assessment.
      Issues of treatment regimens, adherence, confidentiality, social support, and
      nondiscrimination are critical concerns when serving this population.

PMID- 10932848
TI  - Why didn't I go to Durban?

PMID- 10932850
TI  - Indirect amperometric detection of underivatized amino acids in microcolumn
      liquid chromatography with carbon film based ring-disk electrodes.
AB  - An indirect amperometric detection of underivatized amino acids has been
      developed using a carbon film based ring-disk electrode (CFBRDE) in microcolumn
      liquid chromatography (LC). Bromide present in the mobile phase could be
      efficiently oxidized to bromine at the upstream (disk) electrode, and was
      subsequently detected at the downstream (ring) electrode. Most of the
      underivatized amino acids that are electroinactive under conventional
      amperometric conditions react rapidly with the electrogenerated bromine, the
      concentration of amino acids can therefore be indirectly determined by
      continuously monitoring the reduction current of bromine. The signal monitored at
      the downstream electrode was largely dependent on the bromide concentration in
      the mobile phase. Under optimized conditions, the response linearly increased
      with the concentration for most of the amino acids over a concentration range of
      1-100 microM, with a correlation coefficient of 0.990-0.993. The detection limits
      for most of the amino acids were below 1 microM (0.2 pmol). It was demonstrated
      that detection with a ring-disk electrode offers the advantages of achieving a
      much higher collection efficiency caused by a decrease in flow rate in the
      microcolumn LC.

PMID- 10932851
TI  - A remote flow cell for UV absorbance detection with capillary HPLC based on a
      single strand fiber optic.
AB  - A remote flow cell based on a single strand of fused-silica fiber optic was built
      for UV absorbance detection with a packed capillary HPLC system, using
      commercially available pumps, detection electronics (Shimadzu) and fittings. This
      'off-column' flow cell design is applicable to both pressure and electro
      osmotically driven systems. The goals were to minimize the linearity and light
      leakage problems that often limit the performance of UV absorbance detection with
      capillary chromatography. A linear dynamic range of 10(3) (reserpine, lambda =
      220 nm), and a concentration detection limit of 5.1 x 10(-8) mol l-1 were
      observed. Baseline noise was measured at 3.5 x 10(-5) absorbance units (AU), with
      a standard deviation of 1.7 x 10(-5) AU. The illuminated volume of approximately
      3 nl was optimized for capillaries with inner diameters in the range 50-100
      microns, and flow rates from 100 nl min-1 to 1 microliter min-1. These
      modifications of readily available instrumentation have allowed the construction
      of a practical system for fractionating complex mixtures of peptides in small
      amounts, prior to mass spectrometry or additional wet chemistry steps.

PMID- 10932849
TI  - Enantioselective supercritical fluid chromatography using ristocetin A chiral
      stationary phases.
AB  - Racemic mixtures of five acidic drugs have been successfully separated by
      supercritical fluid chromatography (SFC) using macrocyclic antibiotic chiral
      stationary phases (CSPs). A ristocetin A CSP has been prepared 'in-house' and
      effectively applied in packed capillary SFC to separate the enantiomers of
      dichlorprop (R(s) = 1.4), ketoprofen (R(s) = 0.9) and warfarin (R(s) = 0.9). The
      commercial ristocetin A CSP (Chirobiotic R) was subsequently studied in packed
      column SFC with similar results where the enantiomers of warfarin (R(s) = 2.2),
      coumachlor (R(s) = 2.5) and thalidomide (R(s) = 0.6) were separated.
      Interestingly, differences were observed between the two differently immobilised
      CSPs where the enantiomers of dichlorprop and ketoprofen, which were separated on
      the 'in-house' CSP, could not be separated on the commercial phase.

PMID- 10932852
TI  - Derivatization of tertiary amphetamines with 9-fluorenylmethyl chloroformate for
      liquid chromatography: determination of N-methylephedrine.
AB  - The fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) was evaluated for
      the derivatization of tertiary amphetamines prior to liquid chromatographic
      analysis. Conditions for the derivatization were investigated, including the
      reaction time, the derivatization reagent concentration and the pH, using N
      methylephedrine as a model compound. On the basis of these studies, a method for
      the quantification of N-methylephedrine is presented. The method involves
      derivatization with FMOC at ambient temperature and separation of the derivatives
      formed on a LiChrospher C18, 5 microns, 125 x 4 mm id column using acetonitrile
      water gradient elution. The proposed procedure shows good linearity, accuracy and
      reproducibility in the 1.0-25.0 micrograms mL-1 concentration range. The limit of
      detection was 0.1 microgram mL-1 and the limit of quantification was 0.5
      microgram mL-1. The utility of the assay was demonstrated by determining N
      methylephedrine in water and urine samples.

PMID- 10932853
TI  - High-performance liquid chromatographic assay of erythromycin from biological
      matrix using electrochemical or ultraviolet detection.
AB  - Two chromatographic methods were developed for the determination of erythromycin
      A (EA) residues in animal tissues (muscle, liver, kidney and fat of cattle, pigs
      and poultry) and cow's milk. In addition to a more traditional method using
      electrochemical detection, we developed an original alternative method based on
      UV detection at 236 nm, by pretreating to create a chromophore in the molecule.
      An internal standard was used with both methods to check the variability of the
      analytical system. Analysis times and performance were compared. The recovery of
      EA from various matrices was greater than 95%. For both methods the
      quantification limit for EA was 0.25 microgram ml-1 for plasma, 0.025 microgram g
      1 for milk and 0.125 microgram g-1 for the other biological matrices. The methods
      can be used to check for EA residues in these matrices; in fact, the statutory
      maximum residue limits (MRLs) of EA are 0.4 microgram g-1 in muscle, kidney,
      liver and fat of beef cattle, sheep, pigs and poultry, and 0.04 microgram g-1 in
      cow's and sheep's milk.

PMID- 10932854
TI  - Electrophoretic behavior study and determination of some active components in
      Chinese medicinal preparations by capillary electrophoresis.
AB  - The determination of icariin (IC), rhein (RH), chrysophanol (CH), physcion (PHY),
      glycyrrhetic acid (GE), and glycyrrhizic acid (GI), in traditional Chinese
      preparations, Anshen Bunao oral liquid and Maren pill, has been investigated by
      micellar electrokinetic capillary electrophoresis. With borate buffer (10 mM),
      SDS (20 mM) and acetonitrile (10%) as background electrolyte (pH 9.55), 20 kV
      applied voltage and 254 nm UV detection, the six active compounds were completely
      separated within 10 min. The effects of buffer pH, concentration of borate, SDS
      and modifier on electrophoretic behavior and separation are discussed. Regression
      equations revealed linear relationships (correlation coefficients: 0.9960-0.9999)
      between the peak-area of each component and the content. In addition, the levels
      of the six active compounds in two kinds of traditional Chinese medicinal
      preparations were easily determined with recoveries of from 94.7% to 106.4%.

PMID- 10932855
TI  - Measurement of beta-agonist residues in retinal tissue of food producing animals.
AB  - This report presents the results of an investigation on the accumulation of beta
      agonist residues in the retinal tissue of food producing animals. Three different
      species, calf, pig and turkey, were treated with six different beta-agonists and
      analysed for beta-agonist residues in retinal tissue applying a newly developed
      retina preparation procedure which provides sufficient sample material for
      multiple analyses. The results show that all selected beta-agonists accumulate in
      the retina, though in varying concentrations. The results are discussed on the
      basis of existing binding theories and with regard to their impact on the
      existing residue control strategy for beta-agonists.

PMID- 10932856
TI  - Flow injection-pulse amperometric detection of ephedrine at a cobalt
      phthalocyanine modified carbon paste electrode.
AB  - Direct detection of ephedrines and other underivatized amino compounds (amines,
      alicyclic amines, alkanolamines, and amino acids) can be carried out via
      electrocatalytic oxidation at a carbon paste electrode (CPE) modified with cobalt
      phthalocyanine (CoPC) in alkaline solution (0.10 mol L-1 NaOH). Most of the amino
      compounds tested could be determined using the CoPC/CPE in an amperometric flow
      detector. The analytical signal of ephedrine was stabilised by alternating the
      potential between an anodic detection potential of +0.30 V (+0.45 V for other
      amino compounds) applied for 220 ms and a cathodic reactivation potential of 
      0.30 V applied for 100 ms (potentials versus SCE). The linear response range for
      ephedrine was within 1-100 mumol L-1 and the detection limit was 0.8 mumol L-1
      with a 100 microL sample loop and a typical sampling ra 60 h-1. The signal
      (oxidation peak current) reproducibility was 2-3%. The method was applied to the
      determination of ephedrine in pharmaceutical formulations with results comparable
      to those obtained with a standard spectrophotometric method.

PMID- 10932857
TI  - Application of principal component regression to luminescence data for the
      screening of ciprofloxacin and enrofloxacin in animal tissues.
AB  - A new screening method for the analysis of enrofloxacin and ciprofloxacin in
      edible animal tissues is described. The method is based on the application of
      principal component regression to luminescence measurements after reaction of
      quinolones with terbium(III) in a micellar medium. The method was used, first, to
      discriminate between quinolone-containing or quinolone-not-containing samples
      (concentration below the detection limit) and, then, to quantify the sum of both
      analytes. Standards in a pure-water matrix, using the first three principal
      components, were used for the determination. RRMSE range from 4 to 10% depending
      on the analyte. Calibration was successfully applied to the analysis of spiked
      chicken and trout muscle at concentrations between 10 and 50 micrograms kg-1.

PMID- 10932859
TI  - Trace determination of carbendazim, fuberidazole and thiabendazole in water by
      application of multivariate calibration to cross-sections of three-dimensional
      excitation-emission matrix fluorescence.
AB  - The simultaneous determination of carbendazim, fuberidazole and thiabendazole was
      accomplished by cross-section (CS) fluorimetry in combination with multivariate
      calibration algorithms. The total luminescence information of the compounds was
      used to optimise the linear trajectories of the CS. A comparison between
      principal component regression (PCR) and two partial least squares (PLS)
      algorithms, PLS-1 and PLS-2, with different pre-processing methodologies was
      made. The final model, which applied the PLS-1 method, built using pesticide
      standard and emission spectra, was successfully used for the determination of
      these compounds in synthetic mixtures. However, a different PLS-1 multivariate
      calibration model, based on CS through the total luminescence spectroscopic data,
      was necessary for determining the cited pesticides in water samples. Mean
      centring was the best pre-processing technique in both PLS-1 models. This later
      calibration model was built from ultra-pure water samples spiked with known
      carbendazim, fuberidazole and thiabendazole concentrations, after solid-phase
      extraction (SPE). The method, which had a precision better than 5%, was shown to
      be suitable for carbendazim, fuberidazole and thiabendazole monitoring in water
      samples at trace levels.

PMID- 10932858
TI  - Use of partial least-squares regression for multicomponent determinations based
      on kinetic spectrofluorimetric data. Simultaneous determination of canrenone and
      spironolactone in urine.
AB  - A new spectrofluorimetric method for the simultaneous determination of canrenone
      and spironolactone in urine is proposed. The method is based on the different
      rates at which the two analytes react with hot sulfuric acid to form a trienone.
      The kinetic spectrofluorimetric data are processed by partial least-squares
      regression. The effects of sulfuric acid concentration and temperature on the
      system under study were also evaluated and the optimum values for carring out the
      reaction were 50% and 50 degrees C, respectively. The method was checked by
      analyzing urine samples that they contained both diuretics. The accuracy and the
      precision of the method were tested. The relative standard errors in the
      quantification of each analyte in all tested samples were 3.69 and 3.59%. The
      proposed method was validated by comparison with a high performance liquid
      chromatographic method for urine samples.

PMID- 10932860
TI  - Ratiometric oxygen sensing: detection of dual-emission ratio through a single
      emission filter.
AB  - A new method and device for the ratiometric measurement of oxygen concentration
      are presented. They are based on the use of a dual-emission oxygen-sensitive dye.
      The method allows the exclusion of the influence of emission overlap. The
      detection of the dual-emission ratio is performed using a single long-pass
      emission filter. The device described is simpler than the widely used lifetime
      instruments and could easily be a stand-alone low-cost instrument.

PMID- 10932861
TI  - Fast urinary screening for paracetamol using on-line microwave assisted
      hydrolysis and spectrophotometric detection.
AB  - A fully automated urinary screening system for paracetamol and its metabolites is
      proposed. The method comprises on-line acid microwave assisted hydrolysis of the
      drug to p-aminophenol followed by reaction with o-cresol in alkaline medium. The
      indophenol blue dye formed can be continuously monitored at 620 nm. The detection
      limit achieved, 0.1 microgram ml-1, allows a high dilution of the samples, thus
      reducing potential interferences from the sample matrix (mainly protein
      degradation during urine hydrolysis). The proposed screening system also
      possesses an adequate selectivity, as the major interferent, epinephrine, is
      tolerated at concentrations higher than those that could be found in the positive
      urine samples. The reproducibility, expressed as relative standard deviation, was
      3.0% and the sample frequency 20 h-1. The reliability of the method was
      established at five concentrations (between 0.5 and 4 times the detection limit).
      Finally, it was applied to the screening of several human urine samples. The
      results obtained were compared with those provided by batch acid hydrolysis, and
      were similar in all instances.

PMID- 10932862
TI  - Application of sample pre-oxidation of arsenite in human urine prior to
      speciation via on-line photo-oxidation with membrane hydride generation and ICP
      MS detection.
AB  - A pre-oxidation procedure which converts arsenite [As(III)] into arsenate [As(v)]
      was investigated in urinary arsenic speciation prior to on-line photo-oxidation
      hydride generation with ICP-MS detection. This sample pre-oxidation method
      eliminates As(III) and As(v) preservation concerns and simplifies the
      chromatographic separation. Four oxidants, Cl2, MnO2, H2O2 and I3-, were
      investigated. Chlorine (ClO-aq) and MnO2 selectively converted As(III) into As(v)
      in pure water samples, but the conversion was inefficient in the complex urine
      matrix. Oxidation of As(III) by H2O2 was least affected by the urine matrix, but
      the removal of excess H2O2 at pH 10 proved difficult. The most appropriate
      oxidant for the selective conversion of As(III) into As(v) with minimal
      interference from the urine matrix is I3- at pH 7. Unlike H2O2, excess oxidant
      can be easily removed by the addition of S2O3(2-). The I3-(-)S2O3(2-) treatment
      on a fortified sample of reconstituted NIST SRM 2670 freeze dried urine indicated
      that arsenobetaine (AsB), dimethlyarsinic acid (DMA), monomethylarsonic acid
      (MMA) and As(v) were not chemically degraded with recoveries ranging from 95 to
      102% for all arsenicals. Sample clean-up involved pH adjustment prior to C18
      filtration in order to achieve efficient As(III) conversion and quantitative
      recoveries of AsB and DMA. The concentrations determined in NIST SRM 2670 freeze
      dried urine were AsB 17.2 +/- 0.5, DMA 56 +/- 4 and MMA 10.3 +/- 0.3 with a
      combined total of 83 +/- 5 micrograms L-1 (+/- 2 sigma).

PMID- 10932863
TI  - New guidance protects against transmission from hepatitis B infected but e
      antigen negative health care workers.

PMID- 10932864
TI  - [Structure of ATP-dependent potassium channels: SUR/Kir6 molecular complex].

PMID- 10932865
TI  - [ATP-dependent potassium channels and insulin secretion: essential but not
      sufficient role].

PMID- 10932866
TI  - [Hyperinsulinemia, a heterogeneous illness].

PMID- 10932867
TI  - [Apollinaire Bouchardat Prize 2000. Immunogenetic approach to type 1 diabetes in
      man].

PMID- 10932868
TI  - [Continuous measurement of blood glucose: invasive methods using glucose
      capture].

PMID- 10932869
TI  - [Blood glucose monitoring by inverse iontophoresis].

PMID- 10932870
TI  - [Continuous monitoring of blood glucose by non-invasive methods].

PMID- 10932871
TI  - [Atherosclerosis: risks and challenges].

PMID- 10932872
TI  - [Diabetes and arterial thrombosis].

PMID- 10932873
TI  - [Hyperglycemia and atherosclerosis].

PMID- 10932874
TI  - [Infections and atherosclerosis].

PMID- 10932875
TI  - [Prevention of ischemic cardiovascular complications in type 2 diabetes].

PMID- 10932876
TI  - [Management of hyperalgesic diabetic neuropathy].

PMID- 10932877
TI  - [Functional insulin therapy in the type 1 diabetic].

PMID- 10932878
TI  - [The diabetic shoulder].

PMID- 10932879
TI  - [Metabolic anomalies after antiretroviral treatment].

PMID- 10932880
TI  - [Development and use of a telemedicine system for medical surveillance of
      diabetic patients].

PMID- 10932881
TI  - [Strengths and limitations of Hba1c determination. The point of view of the
      biologist].

PMID- 10932882
TI  - [Strengths and limitations of Hba1c determination: the point of view of the
      clinician].

PMID- 10932883
TI  - [Should one wait for a blood glucose meter?].

PMID- 10932884
TI  - [Significance of fasting blood glucose and at 17 hours in the type 2 diabetic].

PMID- 10932885
TI  - [Is it necessary to measure the postprandial blood glucose in the diabetic?].

PMID- 10932886
TI  - [Studies on conditions for the culture of rabbit corneal epithelium].
AB  - PURPOSE: Research was aimed at comparison of isolation methods as well as
      determination of growth and differentiation dynamics of rabbit corneal epithelium
      (CE) in vitro. Adhesion, growth and differentiation of CE cells growing on
      collagen membranes were evaluated. MATERIAL AND METHODS: Research was performed
      on the cells of rabbit corneal epithelium isolated mechanically or enzymatically
      (Dispase II) from comeas excised at the edge of limbus. CE cells were cultured in
      media with high or low contents of calcium, with addition of FCS, insulin,
      cholera toxin and EGF. RESULTS: In comparison with mechanical isolation,
      enzymatic isolation yielded 4-5 times more living undifferentiated (CE) cells.
      The highest dynamics of in vitro growth was observed in primary cultures in low
      calcium medium supplemented with the above substances. After 20 population
      doublings cells were differentiated and died. Only few cells on collagen
      membranes adhered to the collagen but did not enter division. CONCLUSIONS:
      Current research allowed for determination of methodology for CE excision and
      isolation. Optimal conditions for in vitro growth have been established. Growth
      dynamics and proliferation of CE in vitro have been evaluated. Growth of CE on
      standard collagen membrane has not been observed.

PMID- 10932887
TI  - [Failures of brachytherapy in posterior uveal melanoma].
AB  - PURPOSE: To estimate the risk factors responsible for unsuccessful treatment of
      melanoma with episcleral plaque brachytherapy. MATERIAL AND METHODS: Based on 23
      cases of choroidal melanoma, in which the eyes had to be enucleated after earlier
      brachytherapy, clinical characteristics of the tumors, type of plaque therapy and
      reasons of enucleation were analysed. Histopathologic examination of enucleated
      eyes was performed by standard techniques and immunohistochemical stains on
      formalin-fixed paraffinembedded tumor tissues. RESULTS: Tumor size is the most
      valuable risk factor for prognosis in plaque brachytherapy of melanoma. The
      direct indications for enucleation were: increase of tumor mass, optic disc
      invasion, consecutive glaucoma and extrascleral extension. Histopathological
      examination revealed 17 mixed-cell melanoma, 4 spindle-cell, 1 epithelioid and 1
      necrotic. Post-irradiation necrosis was found in only 6 tumors. CONCLUSIONS: It
      is very difficult to predict the results of conservative treatment of melanomas
      basing on their clinical characteristics. The aggressive nature of the tumors and
      their resistance to irradiation seem to be the likely explanation of failures.

PMID- 10932888
TI  - [Optic neuritis as the initial manifestation of multiple sclerosis].
AB  - Optic neuritis (ON) may be the initial manifestation of multiple sclerosis (MS).
      We report on a partially retrospective (1960-1984) and longitudinal study (1985
      1995) of patients with MS that had earlier ON. The study group (ON + MS)
      comprised 173 confirmed cases of ON, the control group (MS) included 767 MS
      patients without history of initial ON. The time lapse from ON to MS was less
      than 5 years in 128 patients (73.99%), 6-10 years in 37 (21.39%) and more than 10
      years in only 8 (4.62%). ON does not affect the course of MS, age at onset,
      duration of disease or life expectancy. Disability status (EDSS) in both groups
      was similar although EDSS progression was somewhat slower and the relapse rate
      per year was lower (0.37) in group ON + MS. We conclude with respect to survival
      and relapse rate that ON is a prognostically somewhat favorable manifestation of
      MS.

PMID- 10932889
TI  - [Functional results in children with retinopathy of prematurity stage 4 and 5].
AB  - AIM OF THE PAPER: To investigate the structural and functional results in
      children with retinopathy of prematurity stage 4 and 5. MATERIAL AND METHODS: 91
      children with ROP stage 4 and 5 were observed by the authors in years 1990-1998.
      In all patients the clinical course of the disease, visual acuity and binocular
      vision were examined during follow-up. RESULTS: Most patients with ROP stage 4
      and 5 are blind or practically blind, even the children in whom only stage 4a was
      diagnosed. CONCLUSION: Prognosis for vision in children with ROP stage 4 and 5 is
      poor and all methods of surgical treatment of retinal detachment should be
      performed in these children to safeguard some kind of useful vision in some
      patients.

PMID- 10932890
TI  - [Hormonal changes in male patients with primary open angle glaucoma].
AB  - INTRODUCTION: Primary open angle glaucoma (POAG) is the most common type of
      glaucoma, pathogenesis of which is not completely known. Several clinical studies
      show that glucocorticoid hormones may be implicated in the pathogenesis of POAG
      and ocular hypertension. Glucocorticoid receptors have been identified in human
      outflow tissue of the eye. AIMS: The purpose of this study, therefore, was to
      evaluate the serum concentration of total cortisol (TF), total testosterone (TT),
      free testosterone (FT), FSH (follitropin), LH (lutropin), ACTH
      (adrenocorticotropin), SHBG (sex hormone-binding globulin), DHEA-SO4
      (dehydroepiandrosterone sulfate) as well as free cortisol (UFF) and 17-OHCS in 24
      hours urinary samples in patients treated because of POAG. PATIENTS AND METHODS:
      Studies were performed in the group of 30 male patients, aged 55 +/- 13 years,
      treated because of glaucoma for more than two years. Serum and urinary
      concentration of hormones were studied using RIA methods (DPC). RESULTS: The
      serum concentration of TF (652.03 +/- 315.43 nmol/l), UFF (248.75 +/- 99.39
      nmol/l) and 17-OHCS (5.47 +/- 2.64 mg/24 h) in urine was increased compared with
      control group. There was not significant difference in concentration of pituitary
      gonadal axis hormones in glaucomatous and control groups of patients. CONCLUSION:
      The results could point to the fact that changes in the endocrine system are one
      of the factors involved in the pathogenesis of POAG. We conclude that an elevated
      level of cortisol, free cortisol and its metabolites is closely related to the
      POAG.

PMID- 10932891
TI  - [Application of numeric integration in waveform morphology of visual evoked
      potentials in optic nerve diseases. Numeric integration method].
AB  - PURPOSE: Presentation of new waveform analysis of pattern and flash visual evoked
      potentials (VEPs) in patients with optic neuropathy. MATERIAL AND METHODS: The
      study involved 48 patients with acute optic neuritis (2nd group), 60 patients
      with demyelinating (3rd group), 32 patients with compressive (4th group), 24
      patients with nonarteritic anterior ischemic optic neuropathy (5th group) and 32
      healthy subjects (1st group). Using computer system UTAS E-1000 (pattern and
      flash stimulation) the VEPs tests were performed. Amplitude, latency of 8 VEP
      components, 4 gradients, mean waveform and 16 areas of numeric integrals were
      calculated. Results were analysed with the use of AN-STAT software. RESULTS:
      Statistical difference recorded under pattern stimulation was obtained in latency
      of 3rd, 4th, 5th components of VEP in comparing 3th and 4th groups, as well as
      amplitude of 3rd waveform, second gradient, areas of integrals between cursors
      number 2 and 4 in comparing 3rd and 5th groups (p < 0.001). Statistical
      difference recorded under flash stimulation was obtained in latency of 4th
      component in comparing 2nd and 5th groups, in amplitude of 7th waveform, areas of
      integrals covering 160 and 224, 224 and 256 ms, between cursors number 2 and 4 in
      comparing 4th and 5th groups, as well as in a range of areas of integrals
      covering 160 and 192 ms in comparing 4th and 5th groups (p < 0.001). CONCLUSION:
      Results prove clinical potency of the presented new comprehensive method in
      analysis of VEP in optic nerve diseases.

PMID- 10932892
TI  - [Assessment of the retinal blood flow by DRG retina Doppler in primary open angle
      glaucoma and normal tension glaucoma].
AB  - PURPOSE: The aim of the study was to evaluate the blood flow in central retinal
      artery (CRA) in primary open angle glaucoma (POAG) and normal tension glaucoma
      (NTG). MATERIAL AND METHODS: Two groups of patients were examined: I group
      consisted of 15 patients (19 eyes) with POAG, II group of 16 patients (32 eyes)
      with NTG. The controls were age-matched healthy persons. Blood flow velocities
      and resistance index in central retinal artery were measured by DRG Retina
      Doppler. RESULTS: We found decreased blood flow velocity in CRA in most of the
      patients with NTG and in part of the patients with POAG. Significant increase of
      resistance index was found only in NTG group. CONCLUSION: Our study confirmed
      that assessment of the blood flow in central retinal artery appears to be a
      valuable method in diagnosis of neuropathy mechanism in glaucoma.

PMID- 10932893
TI  - [Implantation of black diaphragm intraocular lenses in congenital and traumatic
      aniridia].
AB  - PURPOSE: To evaluate the safety and efficacy of the black diaphragm intraocular
      lens (IOL) implantation for the treatment of congenital and traumatic aniridia.
      MATERIAL AND METHODS: Seven black diaphragmatic IOLs were implanted in the eyes
      of 6 patients between 1997 and 1998. There were 5 males and 1 female. The mean
      age of them was 42.8 years (range: 22-54 years). Follow-up ranged from 9 to 20
      months (mean: 14.2 months). Traumatic aniridia was present in 4 eyes and
      congenital aniridia in 3 eyes. Pars plana vitrectomy was combined with the simple
      outside-in method of scleral fixation of IOLs in 6 cases. Three of these eyes
      were aphakic (all with traumatic aniridia) and in 3 eyes (two congenital cases,
      one traumatic case) subluxated lens was simultaneously removed. In one case of
      congenital aniridia with mature cataract, ECCE and ciliary sulcus implantation
      without scleral fixation were performed. RESULTS: There were very few
      complications. Ciliary sulcus bleeding appeared in 2 cases during scleral
      fixation. Transient post-operative corneal oedema was observed in 2 eyes, raised
      intraocular pressure in 3 eyes, and dispersed blood in vitreous cavity in 2 eyes.
      All IOLs were well centred. The improvement in best corrected visual acuity was
      achieved in 5 cases, while good pre-operative best corrected visual acuity was
      maintained in 2 cases. CONCLUSIONS: Diaphragmatic IOL can be fixated to the
      sclera in cases without capsular support or it can be implanted into ciliary
      sulcus after ECCE. Reconstruction of 5 mm pupil and intraocular correction of
      aphakia enable good visual rehabilitation of patients. The combined procedure of
      pars plana vitrectomy and scleral fixation of diaphragmatic lens is safe and
      effective in traumatic and congenital aniridia.

PMID- 10932894
TI  - [Cataract extraction and lens implantation in glaucomatous eyes after
      trabeculectomy].
AB  - PURPOSE: Presentation of problems connected with an implantation of eye lens
      after trabeculectomy with changed anatomic conditions. PATIENTS AND METHODS: In
      51 cases of patients with cataract and glaucoma, following a trabeculectomy
      operation, ECCE was made by corneal incision and lens implantation into posterior
      chamber. In the analysis, the following were taken into consideration: state of
      the eye before cataract operation, intrasurgical difficulties with necessary
      application of additional surgical actions, evaluation of postoperative course.
      RESULTS: In 41.1% of patients, surgical operations followed a non-typical way and
      the below procedures were necessary: loosening of adhesions, mechanical pupillary
      dilation, tearing off fibrous or stained membrane, iridorrhaphy and pupil
      reconstruction. Posterior chamber lens was implanted in 96% of patients and the
      following acuity was achieved: 0.5-1.0 in 25 eyes, 0.3-0.4 in 13 eyes, 0.02-0.2
      in 10 eyes. There was no acuity improvement in 3 eyes only. CONCLUSIONS:
      Operation posterior chamber lens implantation after trabeculectomy can proceed in
      a non-typical way because of changed anatomic conditions. Postoperative
      functional results depend on the degree of nerve lesion (injury), but they are
      often better than preoperative prognoses indicate.

PMID- 10932895
TI  - [Use of YAG-Selecta laser and argon laser in the treatment of open angle
      glaucoma].
AB  - INTRODUCTION: The falling success rate of ALT (Argon Laser Trabeculoplasty) has
      raised the interest in some new laser techniques, such as q-switched Nd:YAG laser
      trabeculoplasty (Coherent Selecta 7000). The "selective" laser trabeculoplasty
      destroys melanosomes of pigmented trabecular meshwork cells, sparing adjacent non
      pigmented cells and tissues. AIM: Our goal was to establish the IOP lowering
      effect of selective laser trabeculoplasty (SLT--Selecta Laser Trabeculoplasty) in
      comparison with ALT. MATERIAL AND METHODS: We have examined 27 patients (10 men,
      17 women) aged 35-82, with open angle glaucoma and visual field deterioration
      despite maximal tolerated topical therapy (21 patients--POAG, 3--NPG, 1-
      pigmentary glaucoma, 1--pseudoexfoliative glaucoma, 1--juvenile glaucoma). One
      eye of each patient was randomly chosen for SLT, the other eye underwent ALT. In
      each method 50 burns were applied in 180 degrees angle with power settings of 600
      1000 mW for ALT and energy settings of 0.5-1.4 mJ for SLT. The IOP was measured 1
      hour before laser treatment and 1, 2, 24 hours and 3 months after treatment.
      RESULTS: The mean initial IOP in eyes selected for SLT was significantly higher
      (21.26 +/- 4.82 mm Hg) than in eyes selected for ALT (20.26 +/- 4.01 mm Hg), t
      test: p = 0.037. However, there was no statistically significant difference in
      the IOP lowering effect between eyes treated with SLT and eyes treated with ALT.
      The mean IOP drop from the pre-treatment values was -2.85 +/- 4.62 mm Hg after
      SLT and -2.63 +/- 3.60 mm Hg after ALT (t-test, p = 0.84). All values: 2, 24
      hours and 3 months after treatment were significantly lower than pre-treatment
      values in both groups (t-test, p < 0.03). Only in the 1st hour after SLT the IOP
      drop was not significant. There was a significant correlation between the amount
      of pigment on the trabecular meshwork and the IOP fall (U Mann-Whitney test). In
      SLT group 6 patients (21%) developed mild iritis during 1st day after laser
      treatment, which disappeared after fluorometholon drop therapy. CONCLUSION: Both
      methods--SLT and ALT--have equivalent IOP lowering effect in short time
      observation (3 months). Due to entirely novel mode of Selecta laser action, long
      term results may show significant differences.

PMID- 10932896
TI  - [Extremely advanced basal cell carcinoma in periocular region: a case report].
AB  - A case of extreme basal cell carcinoma affecting eyelids region in a 66-year old
      man is presented. Long time duration, large destruction of the face tissues and
      histopathological type of metatypic basal cell carcinoma (bcc) eliminated any way
      of therapy (surgery, radiotherapy, chemotherapy). We present this case because
      bcc as localy invasive tumor with low growth, diagnosed and treated at early
      stage can lead to complete recovery.

PMID- 10932897
TI  - [Goniodysgenesis associated with Rubinstein-Taybi syndrome].
AB  - Rubinstein-Taybi syndrome is a constellation of clinical findings characterized
      by mental and motor retardation, broad thumbs and broad first toes, typical
      facies. Ocular and adnexal abnormalities are quite common and include
      antimongoloid slant of the palpebral fissures, epicanthal folds, congenital
      obstruction of the lacrimal excretory system, ptosis, strabismus, congenital
      cataract and congenital glaucoma. The authors describe the case of a 1-year-old
      male with the Rubinstein-Taybi syndrome associated with unilateral congenital
      glaucoma. The case emphasizes the importance of detailed complete ocular
      examinations in patients with Rubinstein-Taybi syndrome, and also highlights the
      occurrence of ocular abnormalities rarely associated with this disease.

PMID- 10932898
TI  - [A case of a patient with immune ring of cornea].
AB  - A case of an 8-year-old girl with immune ring is presented. Immune reaction in
      the cornea after the second assault of the same antigen, probably HSV, produced
      immuno-complexes deposited in the cornea as a ring-shaped lattice. In our case
      the girl was admitted to hospital because of blurred vision, corneal deposits in
      the shape of a ring with keratomycosis suspicion in the eye. 3 months before she
      suffered from a minor injury to this eye (corneal abrasion with a finger while
      playing). Immune ring was recognised. Following Missoten's recommendations the
      girl was treated mainly with topical steroids (ophticor) every 15 minutes on the
      first day until the afternoon, subsequently with dexamethasone 4 times a day--for
      10 days with decreased frequency continuously in an amount stopping the immune
      reaction. After 3 days the regression of deposits and the visual acuity improved.
      I believe this disease is not rare but rarely recognised and my aim is to
      approach this problem more thoroughly.

PMID- 10932899
TI  - [Devic disease: a rare cause of retrobulbar optic neuritis: a case report].
AB  - A case of 58-year-old woman with recurrent retrobulbar optic neuritis (ron) and
      transverse myelitis is presented. The patient was admitted to the opthalmology
      unit because of acute right retrobulbar optic neuritis. In 1997 she complained of
      left retrobulbar optic neuritis. One year later transverse myelitis of thoracic
      spine with spastic paraparesis occurred. MRI examination showed T2 hyperintensive
      focus in the thoracic spine (Th8-Th9, probably demyelinisation). Nowadays MRI
      examination of the optic nerves and brain showed demyelinisation focus in the
      right optic nerve. There was no pathological changes in the brain. The diagnosis
      of Devic disease was established. Treatment with intravenous methyloprednisolon
      was administered with slight improvement. The pathology and clinical course of
      Devic disease are discussed.

PMID- 10932900
TI  - [Differences between the so-called Szczecin-localization method of treating the
      squint and the traditional methods].
AB  - The author shows the differences which have arisen between the methods for the
      last 35 years. The differences concern both the conservative and surgical
      treatments. Differences in the treatment of the squints in adults and infants in
      the first year of life are discussed. The author also presents discrepancies in
      the criteria of cure.

PMID- 10932901
TI  - Anti-HCV antibodies are detectable in the gingival crevicular fluid of HCV
      positive subjects.
AB  - AIMS: To verify the possible of identifying HCV-positive subjects by assaying
      hepatitis C immunological markers in the gingival crevicular fluid. METHODS: Ten
      HCV-EIA-positive subjects and ten HCV-EIA negative subjects were enrolled. One
      specimen each of blood, saliva and gingival crevicular fluid were collected from
      each subjects, and anti-HCV antibodies determined using a rapid test described
      elsewhere. RESULTS: The test was highly sensitive and specific (100%) on whole
      blood, but unable to detect anti-HCV antibodies in any specimen on whole saliva;
      anti-HCV antibodies were detected in about 80% of gingival crevicular fluid
      specimens from HCV-positive subjects, suggesting that the HCV virus and anti-HCV
      antibodies may enter the pounth in the gingival crevicular fluid and then spread
      outside the mouth via the saliva. CONCLUSIONS: The gingival crevicular fluid
      could be a valid alternative to blood for detection of HCV-positive subjects; in
      association with the HCV rapid test this may be a useful procedure for use in
      routine dental practice.

PMID- 10932902
TI  - [A new "light" maxillomandibular fixation system].
AB  - BACKGROUND: A new "light" maxillo-mandibular fixation system for treatment of
      mandibular fractures, based on use of special pins, is proposed. METHODS: Fifteen
      patients with non-displaced mandibular fractures (angle, body and symphysis),
      have been treated at the Department of Maxillofacial Surgery, S. Paolo University
      Hospital, Milan. The system is based on pins formed by a no. 1 metal wire and a
      bead. The free end of the pin is threaded around a tooth and then wound three or
      four times around the bead to fix it in place and, at the same time, separate it
      from the gingiva. One pin is usually positioned on each quadrant. Once the pins
      are in place they are tied to each other using a loop no. 0 to complete the
      maxillo-mandibular fixation. Particular attention was paid to maintain a correct
      individual occlusion. The time of maxillo-mandibular block was 10-15 days.
      RESULTS: Results were good with complete healing of all fractures, restoration of
      individual occlusion, minimal periodontal lesions and a good compliance for the
      treatment by the patients. CONCLUSIONS: It is suggested to use this system
      routinely because quick, economic, easy on periodontium and relatively
      comfortable for the patients. The contraindication include an unstable occlusion,
      the absence of a suitable pair of teeth on both sides of the jaws, avulsion or
      trauma or periodontopathy of one of the teeth needed for the fixation system.

PMID- 10932903
TI  - [Analysis of morphological variations of the maxilla in unilateral complete cleft
      lip and palate after presurgical orthopedic treatment by a functional obturating
      plate].
AB  - BACKGROUND: The authors' aim is to show, through a morphological analysis, how
      the use of a passive functional plate in hard acrylic resin can guide the growth
      of the maxillary segments in babies born with cleft lip and palate. METHODS: The
      authors have obtained, with a scanner gray scales, bidimensional monochromatic
      images of nine babies' dental casts with cleft lip and palate at birth and at the
      time of the first cheilo-rhinoplastic surgery. A graphic analysis on these images
      was made comparing the charts drawn by Bolter's points identified on the
      maxillary alveolar arch. RESULTS: The overlapping of the graphic analysis of the
      mean of values recorded at birth and after the application of the functional
      passive plate in hard acrylic resin shows how it is possible to promote the
      growth of maxillary alveolar arch with unilateral complete cleft. CONCLUSIONS:
      The authors believe that the presurgical orthopedic functional treatment can lay
      the bases for a symmetric and balanced skeletal growth of the cleft maxillary.
      This treatment will promote a better future occlusal relationship. It's also
      pointed out how this functional approach can favour plastic surgery in reducing
      cleft's size.

PMID- 10932904
TI  - [Sports activities and maxillofacial injuries. Current epidemiologic and clinical
      aspects relating to a series of 379 cases (1982-1998)].
AB  - BACKGROUND: The constant improvement in the quality of individual life and
      growing interest in sporting activities have resulted in an increased use of
      sport in free time at amateur level. As a result, sports injuries have steadily
      increased since the late 1980s. The aim of this study was to illustrate our
      experience in the treatment of injuries in this particular category. METHODS: The
      series included patients admitted to the Division of Maxillofacial Surgery at
      Turin University over a 15-year period. A total of 379 maxillofacial fractures
      caused by sporting activities were recorded out of a total of 2925 cases. The
      factors examined included: the type of sport, the age and sex of the patient, the
      cause of the injury, the site of the lesion and the treatment. RESULTS: Sports
      injuries represent 12.9% of total injuries. The mean age of patients was 32.1
      years and the male/female ratio was 5.6:1. A range of 36 sports were examined,
      but football (43.5%), cycling (23.4%) and skiing (13.9%) represented 80.9%. The
      injuries observed involved different areas of the face with a prevalence of the
      orbital/zygomatic complex (47.4%) compared to the mandibular region (42%). The
      most important forms of treatment and preventive therapy were examined and a
      comparison was made of their incidence. CONCLUSIONS: The authors conclude by
      emphasizing the importance of prevention in sports injuries.

PMID- 10932906
TI  - [Oral lupus erythematosus. Description and analysis of 11 cases].
AB  - BACKGROUND: The aim of this study is to evaluate all the cases of lupus
      erythematosus with oral involvement coming to the Department of Oral Medicine in
      the last 15 years (1984-1998). METHODS: The files of the Oral Medicine Department
      of the University of Turin have been reviewed to search oral manifestations of
      lupus erythematosus according to international accepted diagnostic criteria.
      RESULTS: A total of eleven patients 7 women (64%) and 4 men (36%) with a mean age
      of 46 years were included. Three patients (27%) had discoid lupus erythematosus
      (LED) whereas 8 (73%) had systemic lupus erythematosus (LES). In four patients
      the diagnosis of lupus was made after oral diagnosis, whereas 7 patients (64%)
      had a previous diagnosis of lupus. Clinical aspect was typical in 8 cases (73%)
      while one patient had leukoplakia-like white patches and two patients (18%) had
      lichen-like oral lesion. CONCLUSIONS: This study suggest that primitive oral
      lesion of lupus are quite rare but frequently may have atypical features often
      difficult to differentiate from lichen planus.

PMID- 10932905
TI  - Tetracycline fibres used to control bacterial infection during guided tissue
      regeneration (GTR).
AB  - AIMS: The colonization of suspected periodontal pathogens during the healing of
      periodontal defects treated by guided tissue regeneration (GTR) with e-PTFE
      membranes and tetracycline fibers was investigated. METHODS: Fifteen patients,
      each with one pair of angular periodontal bone defects of comparable size and
      morphology were recruited for the study. In a matched-pair study design, the test
      defects were treated with e-PTFE membranes in combination with tetracycline
      fibers, while control defects were treated with e-PTFE membranes alone.
      Microbiological specimens were taken from control as well as from test sites
      preoperatively (T0), intraoperatively (T1), two weeks after surgery (T2) and from
      membranes at time of removal (T3). Cultural methods were used to identify the
      following species: Porphyromonas gingivalis (Pg), Prevotella intermedia (Pi),
      Fusobacterium nucleatum (Fn) and Actinobacillus actinomicetemcomitans (Aa).
      RESULTS: At baseline and T1, none of the suspected periodontal pathogens were
      detected at test or control sites. Levels of P. intermedia and F. nucleatum, as
      mean percentages of total culturable microflora, were detected at levels
      significantly higher in control sites than test sites at times T2 and T3.
      CONCLUSIONS: Findings from this study suggest that e-PTFE membranes are
      frequently colonized by periodontal pathogens, and that bacterial colonization of
      healing sites after GTR procedures can be kept under control with a controlled
      delivery system releasing tetracycline.

PMID- 10932907
TI  - [Major aphthous stomatitis (Sutton's disease): etiopathogenesis, histological and
      clinical aspects].
AB  - Major aphthous stomatitis (Sutton's disease) is a clinical variant of recurrent
      aphthous stomatitis differentiated by its high level of morbidity. It is
      generally found in areas of non-keratinized mucosa and is characterised by the
      presence of necrotic giant ulcers accompanied by intense pain. While this
      pathology has been the subject of molecular studies, its etiopathogenesis is
      still unknown. The most widely accredited hypothesis is that it represents an
      immune mechanism, namely the immunological response of mucosa with antigenic
      anomalies, modulated by altered local reactivity and influenced by triggering
      factors. After an extensive review of the various etiopathogenetic hypotheses,
      clinical and pathological aspects, the authors outline a number of therapeutic
      protocols including the use of topical and systemic cortisone, immunomodulators
      and alternative therapies like laser and ultrasound, or medications to protect
      the ulcers. They stress that the lack of etiopathogenetic uniformity precludes
      any specific treatment.

PMID- 10932908
TI  - [Synovial chondromatosis of the temporomandibular joint].
AB  - Synovial chondromatosis is an uncommon monoarticular proliferative disease of the
      synovium characterized by loose bodies developed in the synovial membrane. The
      literature is reviewed and two cases of synovial chondromatosis of the
      temporomandibular joint characterized by swelling, pain and limitation of
      mandibular movement are reported. Radiographic evidence of loose bodies may or
      may not be present. Computed tomography (CT) or magnetic resonance (MR) might be
      helpful in the diagnosis of synovial chondromatosis. The treatment of choice of
      synovial chondromatosis is surgical and the loose bodies should be removed by
      arthrotomy with examination of the joint cavity. In our patients, no recurrence
      had occurred according to other authors' experience.

PMID- 10932909
TI  - [Topical treatment of peri-implantitis with metronidazole dental gel 25%.
      Clinical analysis and microbiological control].
AB  - BACKGROUND: Aim of this research is to verify the efficacy of metronidazole
      dental gel 25%, used as a topical antibiotic for the treatment of peri
      implantitis. The efficacy of the medicine in the starting phase of the disease
      (mucositis), as well as during peri-implantitis involving bone-bearing loss has
      been evaluated. METHODS: Twenty patients were chosen as a sample for the study.
      After careful evaluation of the several protocols concerning peri-implantitis
      treatment, some diagnostic clinical parameters have been recorded for each
      patient and metronidazole dental gel 25% (Elyzol Cabon) has been administered in
      two applications at perimplants pocket (one after a week). For each patient 3
      microbiological drawings were made for the evaluation of the bacterial population
      around the implant site. RESULTS: From the microbiological examination a decrease
      of Gram- and an increase of Gram+ which returned in almost all the patients to
      normal levels have been observed; moreover, in all the patients a gradual
      decrease of PMN, resolution index of the inflammatory process was obtained,
      confirmed also by a remarkable improvement of all the observed diagnostic
      parameters, except for the peri-implants bone radiotransparency which was
      unchanged. CONCLUSIONS: The research showed that the peri-implant diseases can be
      positively resolved by using the metronidazole dental gel 25% topical antibiotic.
      This drug led to a 60-70% decrease of Gram-, and 40-50% increase for Gram+,
      bringing these back to normal values in almost all the patients. Moreover, a good
      recovery of the peri-implants soft tissues has been observed.

PMID- 10932910
TI  - Health care provider partnership takes action on egregious insurer dominance in
      state.

PMID- 10932911
TI  - An interview with Ronald J. Clearfield, MD. Interview by Charles Cutler.

PMID- 10932912
TI  - Physician-driven program continues to grow.

PMID- 10932913
TI  - Contact capitation: tips for implementation.

PMID- 10932914
TI  - Managing addiction: looking back, looking forward. Interview by Maureen Hoepfer.

PMID- 10932915
TI  - Treatment for atrial fibrillation complications.

PMID- 10932916
TI  - [Guidelines: several principles of the National Program].

PMID- 10932917
TI  - [Narrative approach in clinical practice: competence of tomorrow's physician].

PMID- 10932918
TI  - [Current epidemiological and clinical aspects of tuberculosis: A study in the
      Hospital of Pisa].
AB  - OBJECTIVES: To describe epidemiological and clinical features of tuberculosis
      (tbc) cases identified recently in the Pisa area (Tuscany, Italy). MATERIALS AND
      METHODS: We performed a retrospective study of all cases of tbc notified to the
      Public Health Service in Pisa during January 1996-December 1998. The diagnosis of
      tbc was made following the criteria of the Public Health Ministry. RESULTS:
      Eighty-eight patients affected by tbc were identified. Diagnosis was
      microbiologically proven (positive culture for M. tuberculosis) in 42 patients.
      Sixty-nine patients had pulmonary tbc, 14 extrapulmonary and 5 mixed tbc. Mean
      age was 56.4 years (range 16-87 years). Nineteen patients were extra European
      Community citizens. The incidence of tbc (N./100,000) was 8.4 in 1996, 10 in 1997
      and 3.2 in 1998. In 5.7% of the cases tbc was associated with advanced HIV
      infection. The chest X-ray showed pleural effusion in 12 patients and cavitation
      in 26 patients. Fever was not present in 36.4% of the patients at the moment of
      diagnosis. 12% of the isolated strains of M. tuberculosis were in vitro multidrug
      resistant. CONCLUSIONS: The data presented showed an important rate of tbc in
      Pisa, similar to the incidence of tbc reported by other studies carried out on a
      national scale. We have yet to understand if the decreased rate observed in 1998
      represents a new trend. The isolation rate of multidrug-resistant strains of M.
      tuberculosis in Pisa seems higher than the rates reported in other geographical
      areas. Therefore monitoring of M. tuberculosis susceptibility to antimicrobial
      agents is necessary.

PMID- 10932920
TI  - [Disseminated histoplasmosis in patients with AIDS. 2 case reports].
AB  - Histoplasmosis is endemic in some areas of United States and in South America,
      and generally causes an acute self-limiting respiratory infection. In elderly and
      immunosuppressed patients the infection can spread through the blood, causing a
      severe systemic illness. Here we describe two cases of disseminated
      histoplasmosis in AIDS patients. The first was observed in an Italian woman who
      had never visited endemic countries, and was recognized only at autopsy; the
      second was observed in a trans-sexual patient, arrived in Italy from Brazil.
      Clinical suspicion of histoplasmosis is important in immunocompromised patients
      of non-endemic areas as symptoms are often aspecific and misdiagnosis is
      frequent.

PMID- 10932919
TI  - [Alpha 1-antitrypsin deficiency: the Brescia clinical study].
AB  - In a longitudinal clinical study, two hundred subjects have been evaluated in
      order to identify alpha 1-antitrypsin deficiency patients. According to their
      serum alpha 1-antitrypsin levels, they have been divided into three groups: 25
      patients with severe deficiency (with both pathological alleles--ZZ, SZ or Z and
      rare deficiency allele--and, if clinically suggested, to be treated with
      augmentation therapy), 92 patients with intermediate deficiency (with one
      pathological allele, to be followed up in order to evaluate the risk to develop
      deficiency related disease) and 63 healthy subjects (normal alleles MM). They
      performed lung function test (including cardiopulmonary exercise test and
      methacholine bronchial challenge) chest X-ray and high resolution computed
      tomography, blood tests. Severe deficiency patients also performed perfusional
      lung scan to detect early disorders of blood flow, evaluation of arterial blood
      gases and liver echotomography. Expiratory flow limitation, the prevalence of
      vascular disease, the amount of urine elastin products and correlations between
      the amount of nitric oxide exhaled and bronchial hyperresponsiveness have been
      also investigated. The study showed that in Brescia county the deficiency is more
      common than expected and that evaluation of liver and vessels might be as useful
      as lung function tests. In addition, beneficial effect on local system has been
      observed. The longitudinal study might permit to detect early organ damage and to
      eliminate additive risk factors.

PMID- 10932921
TI  - [Acute disseminated encephalomyelitis as initial clinical manifestation of common
      variable immunodeficiency. A case report].
AB  - Common variable immunodeficiency (CVID) is a primary immunodeficiency disease
      characterized by severe and recurrent infections which affect both lung and
      gastrointestinal systems. On the contrary, central nervous system involvement,
      related to virus infections, is an important, rare and usually fatal complication
      occurring in a later phase of the disease. Furthermore, CVID may predispose to a
      variety of autoimmune diseases. Here, we report the case of a 20 years old girl
      who developed acute disseminated encephalomyelitis as the first clinical feature
      in CVID. The infective agent was not determined and there was no history of
      recent vaccinations. CVID was diagnosed on the basis of the significant reduction
      of serum immunoglobulin concentration, in the absence of either diseases
      responsible for secondary immunodeficiency or functional and/or quantitative
      abnormalities of lymphocyte subsets, phagocytes and complement fractions. The
      treatment with high doses of native intravenous immunoglobulins (IVIG) combined
      with corticosteroids in the early phase led to a complete recovery with
      restitutio ad integrum. This case outlines the possible relationship between
      autoimmune diseases and infections in CVID, as suggested by the finding of either
      viral encephalitis in CVID patients and the well-known autoimmune pathogenesis of
      acute disseminated encephalomyelitis. In such a condition, the combination of
      IVIG and corticosteroids may offer considerable advantages in terms of
      therapeutical efficacy.

PMID- 10932922
TI  - [Antibiotic therapy of otorhinolaryngologic infections].

PMID- 10932923
TI  - [Recurrent polychondritis].

PMID- 10932924
TI  - [Drug therapy of dyslipidemias].

PMID- 10932925
TI  - [Treatment of hypertriglyceridemia. Current aspects].
AB  - The hypertriglyceridemia attends the physiopathology of the atherosclerosis by
      various mechanisms: association of low levels of high density lipoprotein
      cholesterol (HDL-c), modification of quality of low density lipoprotein
      cholesterol (LDL-c), influence on hemostatic processes, association with other
      hazard's factors (obesity, hypertension, etc.). The hypertriglyceridemia
      distinguishes in primary and secondary. In primary forms the origin is
      essentially genetic, while the secondary ones are metabolic consequence of
      various pathologies (renal, thyroid, diabetes mellitus etc.). The
      hypertriglyceridemia's treatment is founded on a correct feeding and/or on
      eventual use of drugs. Apart from the secondary forms, in which is obligatory to
      treat at first the basal disease, the pharmacological therapy of the
      hypertriglyceridemia is suggested only in resistant cases to alone dietetic
      therapy and overall in presence of other factors of atherothrombotic hazard. The
      most utilized drugs are: omega-3 fatty acids, the nicotinic acid and its
      derivatives, the fibrates and the statins. The stronghold of alpha-glucosidases
      inhibitors is the acarbose. It reduces the biosynthesis of very low density
      lipoproteins (VLDL) by the reduction of substrata with an improvement of glucidic
      metabolism. Atorvastatin and cerivastatin develop a greater action to reduce
      serum levels of triglycerides as to the foregoing ones because of the better
      selectivity of receptor binding, the greater halflife and inhibition of the
      apolipoprotein's B100 synthesis.

PMID- 10932926
TI  - [Nephrolithiasis].
AB  - The development of efficacious techniques for stone elimination, and in
      particular of extracorporeal lithotripsy, slackened, in the last two decades, the
      pharmacological research on nephrolithiasis, with the result that the currently
      available efficacious drugs are very few. Instead, the recent elucidation of some
      relevant etiopathogenetic aspects, with special reference to the quantitative and
      qualitative changes of specific urinary inhibitors of crystallization, could open
      new therapeutic avenues for many lithiasic forms, now considered idiopathic.

PMID- 10932928
TI  - [Preventive verapamil therapy in cluster headache].

PMID- 10932927
TI  - [Histoplasmosis: not only a tropical disease].
AB  - Histoplasmosis is a fungal infection resulting from inhalation of spores from the
      fungus Histoplasma capsulatum; it is known to be endemic in various parts of the
      world, especially in North and Latin America, and can produce a spectrum of
      illness, from subclinical infection to progressive disseminated disease. The
      majority of infected persons have an asymptomatic, self-limiting illness.
      Clinical pneumonia occurs in those with exposure to a large number of infecting
      spores. Disseminated histoplasmosis usually occurs in immunosuppressed patients
      or in patients with chronic illness. Diagnosis is best made by visualization of
      yeast in tissue or by culture. In most cases, amphotericin B is the initial drug
      of choice, followed by one of the azoles for lifelong maintenance therapy.
      Itraconazole is the drug of choice for treatment of disseminated histoplasmosis
      in less severe cases, while fluconazole therapy for histoplasmosis is only
      moderately effective.

PMID- 10932929
TI  - Social workers and politics in the new century.

PMID- 10932930
TI  - Reducing welfare benefits: consequences for adequacy of and eligibility for
      benefits.
AB  - During the past two decades, most states have allowed welfare benefit levels to
      erode with inflation. Very little attention has been paid by academics and policy
      makers to the potential effects of the Personal Responsibility and Work
      Opportunity Reconciliation Act of 1996 on welfare benefit levels. This article
      provides a number of explanations for likely reductions in states' welfare
      benefit levels. Consequences of reducing welfare benefit levels are examined. The
      article shows how small changes in benefit levels can alter profoundly
      eligibility for welfare. Social workers need to advocate for increases in welfare
      benefit levels which, at the very least, keep up with inflation.

PMID- 10932931
TI  - Understanding a work-family fit for single parents moving from welfare to work.
AB  - Teng and Pittman's model of "work-family fit" served as a theoretical base for
      exploring the experiences of families moving from welfare to work. Responding to
      open-ended telephone interview questions, 30 recently hired welfare recipients
      described factors that were needed for them to make a smooth transition into
      work, be successful at their jobs, and balance work and family. The individuals
      appeared to experience greater success when their own needs and the needs of
      their families were being met and when they were able to meet the demands of
      work, leading to greater work-family fit. Support from the workplace and other
      community sources, as well as participants' personal attributes contributed to
      this work-family fit. Specific strategies based on these findings are offered for
      employers, social workers, and community organizations.

PMID- 10932933
TI  - The inclusive workplace: an ecosystems approach to diversity management.
AB  - This article's main argument is that organizations need to expand their notion of
      diversity to include not only the organization itself, but also the larger
      systems that constitute its environment. The concept of "the inclusive
      workplace," introduced here, refers to a work organization that is not only
      accepting and using the diversity of its own work force, but also is active in
      the community, participates in state and federal programs to include working poor
      people, and collaborates across cultural and national boundaries with a focus on
      global mutual interests. Using an ecosystems perspective, the article outlines a
      value-based model and a practice-based model of the inclusive workplace as they
      pertain to the different organizational levels, from the micro to the macro.
      Finally, implications for the social work profession are drawn with specific case
      examples for each system level.

PMID- 10932932
TI  - Teenage parents and welfare reform: findings from a survey of teenagers affected
      by living requirements.
AB  - An important component of welfare reform aimed at minor teenage parents is a
      requirement that the teenager live in an appropriate living situation, typically
      with a parent or guardian. The State of Massachusetts developed Teen Living
      Programs as an alternate living arrangement for minor teenage parents receiving
      welfare who are unable to live with family members. This article reports on a
      survey of 199 teenage parents who lived in the Teen Living Programs. Three
      research questions were asked: Who are the teenagers served by these programs?
      What services were provided? To what extent have teenagers attained key outcomes?
      Outcomes measured included educational attainment, employment, welfare status,
      homelessness, and subsequent pregnancy. Implications for social policy, further
      program development, and clinical intervention are discussed.

PMID- 10932934
TI  - The social work ethics audit: a risk-management strategy.
AB  - In recent years, social work's knowledge base related to professional ethics has
      expanded significantly. However, most practicing social workers concluded their
      formal professional education at a time when comprehensive ethics education was
      not a critical or mandated component of the curriculum. This article integrates
      current knowledge on social work ethics and introduces the concept of a social
      work ethics audit to aid social workers in their efforts to identify pertinent
      ethical issues; review and assess the adequacy of their current ethics-related
      practices; modify their practices as needed; and monitor the implementation of
      these changes.

PMID- 10932936
TI  - Infants and toddlers with disabilities: relationship-based approaches.

PMID- 10932935
TI  - Child support policy: some critical issues and the implications for social work.

PMID- 10932937
TI  - Recovered memory therapy.

PMID- 10932938
TI  - Social work and speciesism.

PMID- 10932939
TI  - Social work and speciesism.

PMID- 10932940
TI  - Social work and speciesism.

PMID- 10932942
TI  - Keeping pace with cardiac implants.

PMID- 10932941
TI  - Social work and speciesism.

PMID- 10932943
TI  - Exercising toward diabetes control.

PMID- 10932945
TI  - The role of alternative treatments for cancer.

PMID- 10932944
TI  - Sore throat: when is it serious?

PMID- 10932946
TI  - Why have I developed pulmonary fibrosis even though I don't smoke?

PMID- 10932947
TI  - When should I consider surgery for rectocele?

PMID- 10932948
TI  - Heartburn. Don't ignore the fire.

PMID- 10932949
TI  - Health tips. Fresher breath.

PMID- 10932950
TI  - NIH studying dietary supplements for arthritis.

PMID- 10932951
TI  - Third drug to treat Alzheimer's approved.

PMID- 10932952
TI  - Diabetes advances. New management tools.

PMID- 10932953
TI  - Online pharmacies. Convenient--but safe?

PMID- 10932954
TI  - Outer ear infections. Get treatment early.

PMID- 10932955
TI  - I've had a tingling sensation in my outer thigh. What might this be?

PMID- 10932956
TI  - Can kava supplements help relieve my anxiety?

PMID- 10932957
TI  - Management of acute otitis media.

PMID- 10932958
TI  - Criteria for weaning from mechanical ventilation.

PMID- 10932960
TI  - Scale for identification of "at risk" families for underfive deaths.
AB  - India currently has an infant mortality rate (IMR) of 73 and aims to reach 60 per
      1000 live births by 2000 A.D. The "at risk" approach which has been traditionally
      used for Maternal and Child Health services could help to reduce costs. The main
      objective of the study was to identity socio-demographic "risk factors" at family
      level for underfive deaths and assess the validity and efficiency of a risk index
      scale for this purpose. A computerised database on about 71,000 individuals in 28
      villages in Ballabgarh Block exists since 1987. All the underfive deaths in the
      study area during the period 1991-95 were compared with age and sex matched
      controls on socio-demographic variables. All variables which were found
      significant at 10% level were taken in for logistic regression. The variables
      found significant were used to construct a ten point scale. This scaling system
      was applied to all the families with an underfive child during the two year
      period 1996-97. Validity and efficiency of this approach was calculated. A total
      of 849 cases and their age and sex matched controls were studied. The variables
      which were significantly associated with risk of underfive deaths were: not
      received measles vaccine (2.19; 1.58-3.04), history of sibling death (2.03; 1.19
      3.45), maternal illiteracy (1.86; 1.23-2.81), never used a contraceptive (1.59;
      1.17-2.14), having more than 4 children (1.46; 1.04-2.05). About 40% of houses
      were labelled as high risk. The sensitivity and specificity were around 60%. The
      improvement in efficiency by the risk approach was 33%. Risk approach is helpful
      in identifying families who are at greater risk of having underfive deaths. It
      results in a modest increase in the efficiency of services.

PMID- 10932959
TI  - Hazard analysis and critical control points of weaning foods.
AB  - Hazards and critical control points were identified during the preparation,
      feeding and storage of weaning foods fed to the children (6-24 months) belonging
      to low income group (LIG) families using survey methods, spot and indepth
      observations and microbial analysis. High microbial counts were obtained for the
      weaning food samples procured from the families that were rated as poor for both
      personal hygiene and environmental sanitation. Food samples that were held at
      ambient temperature (25-35 degrees C) showed high counts of coliforms, AMCC,
      yeast and mold, Staphylococcus aureus and Bacillus cereus. Spice mixtures and mop
      samples also revealed high counts for all these organisms. Coliforms were not
      isolated from the water samples of all the 10 households. However, a high count
      of Bacillus cereus (10(3-5)/ml) was observed in water samples of two selected
      households. The hazards and critical control points identified were high initial
      contamination of raw foods, poor environmental sanitation and personal hygiene,
      feeding of overnight moist foods stored at ambient temperature and insufficient
      steaming of these foods.

PMID- 10932961
TI  - Birth weight at Changlang, Arunachal Pradesh.
AB  - The data on birth weight of 524 (male--287, female--237) live born singleton
      babies of Changlang have been subjected to analysis in relation to sex, mean
      birth weight and low birth weight (LBW). For the purpose of comparison, the
      present data were sub-divided into three categories--Tangsa Tribe (T.T.), Tribes
      excluding Tangsa (T) and other groups (O.G.). Tribal babies of Changlang are
      found to be heavier than babies of other groups. It has also been observed that
      occurrence of LBW among tribal babies of Changlang is less than that of the
      babies of other groups of Changlang and it is much less than that of Bengali
      babies of Calcutta and Marathi babies of Pune District. It is apparent that
      tribal babies of Changlang are more healthier than caste babies of N.E. India.

PMID- 10932962
TI  - Hypoglycemia in small for gestational age babies.
AB  - The main objectives of the study were to find the incidence and risk factors
      associated with development of hypoglycemia in small for gestational age (SGA)
      babies, to compare haemoglucotest strips (Boehringer Mannheim) with the standard
      laboratory method (glucose-hexokinase) for estimation of blood glucose, and to
      measure the insulin and cortisol responses of SGA babies. This was a prospective
      longitudinal study. The sample included SGA babies and over a period of six
      months, 127 consecutively born small for gestational age babies were investigated
      prospectively for development of hypoglycemia in first 48 hrs of life. Plasma
      samples were taken during episodes of hypoglycemia for insulin and cortisol
      estimation and compared with non-hypoglycemic controls. The overall incidence of
      hypoglycemia was 25.2% in SGA babies and 98% of the episodes occurred within
      first 24 hrs. Compared to non-hypoglycemics, mothers of hypoglycemic babies had
      higher incidence of receiving i.v. fluids (5% dextrose) during labour. The
      hypoglycemic babies were more likely to be sick and oral feeds had been initiated
      by one hour of life in only 37% of them compared to 63% of non-hypoglycemic
      babies. Plasma insulin/glucose ratio was significantly higher in hypoglycemic
      than non-hypoglycemic babies, whereas the cortisol levels were similar. Small for
      gestational age babies are highly prone to develop hypoglycemia in first 24 hrs
      of life.

PMID- 10932963
TI  - Aerodigestive foreign bodies.
AB  - Accidents with foreign bodies (FBs) are most common within the first two years of
      life. The airway FBs present a diagnostic dilemma as both the history and the
      investigations can be misleading. The persistent hypoxia presents a threat to
      life as does extraction. Moreover, the chemical pneumonitis induced by vegetative
      FB makes the situation even more worse. The FB of digestive tract are
      comparatively benign unless long standing. It is neither necessary for the airway
      FB to present with respiratory symptoms and signs nor for the FB of digestive
      tract to complain of dysphagia/throat pain. Oesophagoscopy may have to be done if
      an esophageal FB is causing only recurrent respiratory infections without
      dysphagia. The situation in dealing with FB varies from site to site in the
      aerodigestive tract. This article stresses the various dubious factors including
      the history, examination and investigation which can lead to misdiagnosis and
      also those problems which are encountered during planned extraction as well as
      post-operatively.

PMID- 10932964
TI  - Insulin analogues and management of diabetes mellitus.
AB  - The introduction of insulin analogues, of which insulin lispro is the prototype,
      marks a very important milestone in the management of patients with diabetes
      mellitus. It differs from regular human insulin in its quicker onset and shorter
      duration of action. In various clinical trials, insulin lispro was found to be
      superior to regular human insulin in controlling postprandial hyperglycemia
      without increasing the risk of hypoglycemia. It improved the quality of life of
      diabetic patients by providing more flexibility to meal plans. Recently, another
      short acting insulin analogue called insulin aspart has been tried in clinical
      studies with benefits similar to insulin lispro. The turn of the millennium is
      now witnessing the development of long acting insulin analogues like insulin
      glargine, which can provide continuous low-level basal insulin concentrations
      similar to natural settings. In this review, we discuss the potential of insulin
      analogues in the modern management of diabetes with emphasis on insulin lispro.

PMID- 10932965
TI  - Diabetes mellitus in newborns and infants.
AB  - Diabetes mellitus is uncommon in infancy and newborn period. The two common forms
      seen are the transient and permanent forms of diabetes mellitus of the newborn.
      They have to be differentiated from the transient hyperglycemic states (Blood
      sugar > 125 mg/dl) seen in newborns who receive parenteral glucose infusions and
      in those with septicemia and CNS disorders. Transient diabetes mellitus of the
      newborn (TDNB) is defined as hyperglycemia occurring within the first month of
      life lasting at least 2 weeks and requiring insulin therapy. Most of these cases
      resolve spontaneously by 4 months. It has a reported incidence of 1 in 45,000 to
      60,000 live births. The most likely etiology is a maturational delay of cAMP
      mediated insulin release. The clinical features include small for datedness,
      proneness for birth asphyxia, open-eye alert facies, dehydration, emaciation,
      polyuria and poydipsia. These children are prone to septicemia and urinary tract
      infections. They have hyperglycemia, glucosuria, absent or mild ketonuria, low
      basal insulin, C-peptide and IGF-1 levels. Treatment consists of hydration and
      judicious administration of insulin with close monitoring. Thirty percent of
      these children are likely to develop permanent neonatal diabetes. Compared to
      transient form, permanent diabetes mellitus is uncommon. It is usually due to
      pancreatic dysgenesis often associated with other malformations and rarely due to
      type 1 diabetes mellitus. The diagnosis is based on the demonstration of both
      exocrine and endocrine pancreatic dysfunction. These children are managed as type
      1 diabetes mellitus. They are prone to develop the vascular complications of
      diabetes at an earlier date.

PMID- 10932966
TI  - Management of undescended testis.
AB  - The term cryptorchidism indicates a testis, which has failed to descend to the
      scrotum and is located at any point along the normal path of descent or at an
      ectopic site. Hormones play a pivotal role in testicular descent except during
      the migration to the level of internal inguinal ring. Cryptorchidism is present
      in about 4.5% of newborns with a higher incidence in preterms. The incidence
      decreases to 1.2% by the first year. It is classified as palpable and impalpable.
      The most common site of an ectopic testis is superficial inguinal pouch.
      Retractile testis is often bilateral and most common in boys between 5 and 6
      years of age. Hypospadias and inguinal hernias are the most common associated
      anomalies seen with undescended testis. A thorough clinical examination helps in
      arriving at the etiology. A short hCG stimulation test helps to exclude anorchia.
      Different imaging techniques are of little help in diagnosis and require the help
      of an experienced radiologist. Laparoscopy has an important role in the diagnosis
      and management of undescended testis. The common complications include torsion
      and atrophy of testis. Infertility is seen in about 40% of unilateral and 70% of
      bilateral cryptorchidism. Undescended testis is 20 to 40 times more likely to
      undergo malignant transformation than normal testis. Both hCG and GnRH have been
      used with limited success in these children. All boys with cryptorchidism should
      be referred to a pediatric surgeon before 2 years of age. These children should
      be followed up every year after surgery to identify testicular tumors.

PMID- 10932968
TI  - Renovascular hypertension treated by renal autotransplantation.
AB  - Renal autotransplantation is rarely performed by surgical procedure for the
      management of renovascular hypertension. We report 2 interesting cases of
      renovascular hypertension which were treated successfully by renal
      autotransplantation.

PMID- 10932969
TI  - Biotinidase deficiency--a treatable entity.
AB  - Biotinidase deficiency is a well recognised treatable cause of a wide spectrum of
      progressive neurological symptoms. Recent reports have stressed the need to
      screen children with early onset of seizures, encephalopathy, neurodevelopmental
      delay, skin rash and alopecia. Enzyme estimation remains the conclusive test. We
      present a patient with biotinidase deficiency suspected on the above clinical
      grounds and diagnosed on the basis of metabolic acidosis, raised blood lactate,
      ketonuria and positive dinitrophenylhydrazine (DNPH) test and confirmed on
      urinary organic acid profile. Supplementation with biotin resulted in marked
      clinical improvement and normalisation of metabolic parameters. Thus the
      clinician should be alert to simple clinical pointers which aid in early
      diagnosis of these disorders.

PMID- 10932967
TI  - The child with micropenis.
AB  - Micropenis refers to an extremely small penis with a stretched penile length of
      less than 2.5 SD below the mean for age or stage of sexual development. It should
      be differentiated from a buried or hidden penis and aphallia. It is important to
      use a standard technique of stretched penile measurement and nomograms for age to
      identify children with micropenis. All children above 1 year of age with a
      stretched penile length of less than 1.9 cm need evaluation. Based on etiology
      they can be classified as hypogonadotropic hypogonadism (hypothalamic or
      pituitary failure), hypergonadotropic hypogonadism (testicular failure), partial
      androgen insensitivity syndrome and idiopathic groups. The help of a pediatric
      endocrinologist, geneticist, pediatric surgeon and/or urologist is often
      necessary. Growth velocity is an important determinant of associated hypothalamic
      or pituitary pathology. GnRH and/or hCG stimulation tests are often helpful in
      evaluating the etiology. Similarly chromosomal studies are indicated in a few.
      Often the diagnosis is inferred by the presence of clinical features suggestive
      of a syndrome usually associated with hypogonadotropic hypogonadism. Irrespective
      of the underlying cause a short course of testosterone should be tried in
      patients with micropenis and an assessment of the penis to respond should be
      made. Transdermal DHT has also been reported to be effective in prepubertal
      children. Children with hypopituitarism and GH deficiency respond to appropriate
      hormonal therapy. Surgical correction is not indicated in the common endocrine
      types of micropenis. Many studies have shown that most testosterone treated
      children have satisfactory gain in length of penis and sexual function. Thus
      sexual reassignment is done very infrequently now.

PMID- 10932970
TI  - Methyl-prednisolone in neurologic complications of Mycoplasma pneumonia.
AB  - In patients with Mycoplasma pneumonia extrapulmonary manifestations such as
      encephalitis, meningitis, cerebellar and brain stem involvement, cranial nerve
      lesions, peripheral neuropathy, polymyositis have been observed. We report a 16
      year-old girl with M. pneumonia infection, acute behavioral changes and coma.
      Treatment with high dose methyl-prednisolone and clarithromycin led to rapid
      clinical improvement.

PMID- 10932971
TI  - Poland anomaly and ulna shortage in two cousins.

PMID- 10932972
TI  - Hypomelanosis of Ito.

PMID- 10932973
TI  - Comments on cystic fibrosis in India.

PMID- 10932974
TI  - Gynaecology in the new millennium.
AB  - Great challenges await the gynaecologist in the 21st century. While advances in
      medical technology necessitate that gynaecology move more towards a medical
      discipline than a surgical one, gynaecologists will be expected to play an
      increasingly important role in the modern woman's life. This fundamental change
      is influenced by four main factors, namely, the world's aging population, spread
      of information technology, advances in molecular based medical therapy, and the
      changing lifestyle of the woman in the next century. Our role cannot get any
      lesser as we continue to advise, educate and facilitate the lives of women, and
      we must aspire a new generation of responsible gynaecologists to continue this
      ambition.

PMID- 10932975
TI  - Laparoscopic management of heterotopic pregnancy: a review.
AB  - Laparoscopic management of ectopic pregnancies is becoming more common. Having
      recently successfully treated one case of heterotopic pregnancy by laparoscopy in
      our department, the object of the present paper is to review the literature
      regarding laparoscopically treated cases of heterotopic pregnancy in order to
      assess benefits, complications and safety of this procedure. A Medline search
      yielded 10 additional cases with ampullary, interstitional or cornual tubal
      pregnancy, respectively. All surgical procedures were uncomplicated and all in
      utero pregnancies progressed normally. Despite a small number of cases, lack of
      complications in these reports is encouraging feasibility of laparoscopic
      management of heterotopic pregnancy.

PMID- 10932976
TI  - The association of transforming growth factor-beta 1 with myometrial invasion of
      endometrial carcinomas through effects on matrix metalloproteinase.
AB  - OBJECTIVE: The association of transforming growth factor-beta 1 (TGF-beta 1) with
      a matrix metalloproteinase (MMP) and a tissue inhibitor of metalloproteinase
      (TIMP), as well as myometrial invasion of endometrial cancer was studied.
      METHODS: The effects of TGF-beta 1 on cellular invasiveness, gelatinase activity,
      and expression of TIMP-1 were examined in 2 endometrial adenocarcinoma cell
      lines, KLE and Ishikawa. Plasma was obtained from 8 endometrial cancer patients
      with Stage-Ia disease, from 6 with Stage-Ib disease, and from 4 with Stage-Ic
      disease, and the levels of TGF-beta 1 were measured by enzyme immunoassays. The
      immunohistochemical expression of MMP-9, TIMP-1, TGF-beta 1, and TGF-beta
      receptor Type I in tumor tissue from the same patients also was detected.
      RESULTS: Invasiveness, gelatinase activity, and the expression of TIMP-1 were
      higher in KLE cells than in Ishikawa cells, and they were increased by treatment
      with rTGF-beta 1. The expression of TGF-beta receptor Type I was higher in KLE
      cells than in Ishikawa cells, which were unresponsive to exogenous TGF-beta 1.
      The plasma levels of TGF-beta 1 were greater in Stage-Ib and Stage-Ic patients
      than in Stage-Ia patients. MMP-9 and TGF-beta receptor Type I were expressed
      mainly in tumor cells, while TIMP-1 and TGF-beta 1 were localized in both tumor
      epithelial cells and stromal cells. MMP-9 and TIMP-1 were expressed only in Stage
      Ib and Stage-Ic patients, although TGF-beta 1 and TGF-beta receptor Type I were
      ubiquitous. CONCLUSIONS: Myometrial invasion of endometrial cancers involves an
      increase in gelatinase activity, regulated to some extent by TGF-beta 1 in an
      autocrine or paracrine fashion.

PMID- 10932977
TI  - Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening
      in native Japanese women.
AB  - OBJECTIVE: This study was conducted to assess the usefulness of dimeric inhibin A
      as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3
      markers for native Japanese women. METHODS: Serum specimens from 367 native
      Japanese women in the second trimester were assayed for dimeric inhibin A levels.
      Day specific dimeric inhibin A medians were established for gestational ages 15.0
      21.9. Weekly median values for the native Japanese were compared with those of a
      U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome
      and 3 trisomy 18 cases were also assayed for dimeric inhibin A. RESULTS: Dimeric
      inhibin A levels did not vary greatly over the gestational age range as expected.
      Median value comparison showed that native Japanese dimeric inhibin A medians are
      higher than the U.S. population medians by an average of 7.95%. Native Japanese
      dimeric inhibin A median values in this study are 1.77 times higher in Down's
      syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A
      levels show no significant difference from the unaffected pregnancies.
      CONCLUSIONS: This report shows for the first time that dimeric inhibin A can be
      informative as a fourth marker for Down's syndrome screening in native Japanese
      women. We expect the addition of dimeric inhibin A to a triple marker protocol
      will increase the accuracy of predicted risk for all pregnancies screened and
      increase the detection rate of Down's syndrome affected pregnancies.

PMID- 10932978
TI  - Reasons for improper simple hysterectomy in patients with invasive cervical
      cancer in the northern region of Thailand.
AB  - OBJECTIVE: To determine the reasons for improper simple hysterectomy in the
      presence of invasive cervical cancer. METHODS: The medical records of 70 patients
      who had undergone simple hysterectomy in the presence of invasive cervical cancer
      and were referred to Chiang Mai University Hospital between January 1991 and
      December 1998 were reviewed. RESULTS: Approximately half of the patients
      presented with abnormal vaginal bleeding. Failure to perform a Papanicolaou smear
      before the operation accounted for 35.4%. Normal pelvic examination in which no
      gross invasive tumor was observed accounted for 59%. The most common indications
      for inappropriate operation was cervical dysplasia. The reasons for inappropriate
      simple hysterectomy included lack of preoperative cervical cytology (22.8%),
      incomplete evaluation of cervical dysplasia or microinvasion on biopsy (21.4%),
      false-negative cervical cytology (18.6%), failure to perform an endocervical
      curettage following conization (8.6%), emergency hysterectomy (8.6%), failure to
      perform indicated conization (5.6%), errors in colposcopic examination (4.3%),
      incomplete evaluation of an abnormal cervical cytology (1.4%), failure to perform
      endocervical currettage following loop conization (1.4%), failure to review slide
      (1.4%), failure to check the pathology report (1.4%), failure to biopsy a gross
      cervical lesion, and skipped lesion in upper part of the endocervix (1.4%). One
      case of invasive disease was missed for unknown reason. CONCLUSION: Most cases of
      inappropriate hysterectomy resulted from deviation from guideline for cervical
      cancer detection. Preoperative Papanicolaou smear and strict adherence to the
      well-established diagnostic protocol for patients with an abnormal smear are
      advised to prevent such occurrence.

PMID- 10932980
TI  - A case report: verrucous carcinoma of the endometrium--the difficulty of
      diagnosis, and a review of the literature.
AB  - A verrucous carcinoma is a subtype of well-differentiated squamous-cell
      carcinomas, arising in the vagina, vulva, and uterine cervix. But a verrucous
      carcinoma very rarely arises in the uterine endometrium. The present paper
      presents a case of a verrucous carcinoma of the endometrium that is described in
      association with the tumor marker SCC; this paper also includes a review of the
      relevant literature.

PMID- 10932979
TI  - Comparison of sex chromosome aneuploidy in spermatozoa of fertile men and those
      requiring ICSI treatment detected by fluorescence in situ hybridization.
AB  - OBJECTIVE: To compare the frequencies of aneuploidy for chromosomes X, Y and 18
      in spermatozoa of infertile and fertile males, using 3-color fluorescence in situ
      hybridization. METHODS: Twelve infertile patients who underwent intracytoplasmic
      sperm injection treatment at Queen's Medical Centre, Nottingham were studied.
      Three fertile men served as controls. Aneuploidy frequencies in both groups were
      compared using 2-sample t-tests. RESULTS: A total of 26,615 ad 93,649 cells were
      scored in the control and infertile groups respectively. The frequencies of
      diploidy, sex chromosome disomy and chromosome 18 disomy in the fertile (0.11,
      0.28 and 0.11%) compared to the infertile males (0.05, 0.18 and 0.06%) were not
      statistically significantly different. CONCLUSION: Our preliminary data do not
      indicate an increased risk from paternal origin sex chromosome aneuploidies in
      ICSI. However, we recommend further investigations of the cytogenetic
      constitution of spermatozoa from severe male factor patients.

PMID- 10932981
TI  - Heavy-for-date infants: their backgrounds and relationship with gestational
      diabetes.
AB  - OBJECTIVE: Gestational diabetes (GDM) is closely related to birth weight. Heavy
      for-date (HFD) infants, especially those with macrosomia, cause many perinatal
      complications. This study was performed to examine the backgrounds of HFD infants
      and to determine such infants' relationship with GDM. METHOD: Eighty cases of HFD
      infants who were delivered from 1996 through 1998 were analyzed. The random blood
      glucose level was used for screening for GDM. RESULTS: Maternal body weight and
      the body-mass index before pregnancy and at delivery and the blood glucose level
      at the second trimester were positively correlated with birth weight. However,
      only 8.8% of HFD cases were detected by this screening method in the first
      trimester, and 11.3% of HFD cases were detected in the second trimester and only
      1 case of borderline-type was detected by subsequent 75-g OGTT. CONCLUSIONS:
      Maternal obesity is an independent and more important risk factor for HFD infants
      than glucose intolerance.

PMID- 10932982
TI  - Post partum splenic artery aneurysm rupture.
AB  - Ruptured splenic artery aneurysm during pregnancy is a rare event with high
      maternal and fetal mortality rate. A case of ruptured splenic artery aneurysm in
      the post partum period is presented. The literature is reviewed on
      pathophysiology, clinical presentation and management of this rare and
      potentially fatal entity.

PMID- 10932983
TI  - Ten years' experience of antenatal mean corpuscular volume screening and prenatal
      diagnosis for thalassaemias in Hong Kong.
AB  - OBJECTIVE: To determine the prevalence of thalassaemia carriers in Hong Kong.
      SUBJECTS AND METHODS: From 1988 to 1997, 25,834 (53.7%) of 48,089 mothers were
      screened for thalassaemias by mean corpuscular volume (MCV) at the first
      antenatal visit. RESULTS: In the screened population of 25,834, 2229 (8.6%) had
      MCV < or = 75 fl. Of these, 1121 (4.3%) were alpha-thal, 715 (2.8%) were beta
      thal, 23 (0.1%) were alpha beta-thal, 57 (0.2%) were other haemoglobin variants,
      and 281 (1.1%) had either iron deficiency or uncertain causes. Out of 200
      pregnancies at risk for homozygous alpha-thal-1 and 32 at risk for beta-thal
      major, 27 homozygous alpha-thal-1 and 7 beta-thal major were identified, compared
      favourably with the expected figures of 23 and 9. CONCLUSION: Antenatal screening
      for thalassaemias by MCV is simple, effective and reliable. Universal screening
      has a different impact as bone marrow or cord blood stem cell transplant provides
      cure for beta-thal major. At risk couples have, as an alternative to termination
      of pregnancy, the option of early detection and treatment for their affected
      newborns or fetuses.

PMID- 10932984
TI  - Adverse pregnancy outcome following post-chorionic villus sampling amniocentesis
      compared to chorionic villus sampling.
AB  - OBJECTIVE: To assess the adverse pregnancy outcome of post-chorionic villus
      sampling (CVS) amniocentesis and chorionic villus sampling. METHODS: Adverse
      pregnancy outcomes of 32 post-CVS amniocentesis cases and 264 CVS only cases were
      compared. The base-line characteristics were comparable in the 2 groups. RESULTS:
      One (3.1%) chromosomal abnormality was detected in the post-CVS amniocentesis
      group, compared to 5 (1.8%) in the CVS only group (p > 0.05). The fetal loss rate
      (spontaneous abortions and stillbirths) among continuing pregnancies was 3.2% in
      the post-CVS amniocentesis group and 3.5% in the CVS only group (p > 0.05). No
      statistically significant difference was found in the incidence of neonatal
      death, preterm delivery, fetal growth restriction, or congenital anomalies
      between the 2 groups. CONCLUSION: Adverse pregnancy outcome occurred at a similar
      frequency in the post-CVS amniocentesis group as in the CVS only group.
      Therefore, a subsequent amniocentesis after CVS can be considered as a safe
      procedure that does not introduce any additional adverse pregnancy outcome
      compared to that of CVS only.

PMID- 10932985
TI  - Chemotherapy in recurrent epithelial ovarian cancer (EOC): an analysis of
      prognostic factors.
AB  - OBJECTIVE: Prognosis of patients with recurrent epithelial ovarian cancer (EOC)
      is generally poor. Cisplatin is the most effective drug. We used three cisplatin
      based chemotherapeutic (CT) regimens and retrospectively analyzed the data to
      determine the response rate, toxicity, survival and the impact of various
      prognostic factors on the outcome. PATIENTS AND METHODS: Between August, 1989 and
      September, 1997, 102 patients were diagnosed to have recurrent EOC. Sixty-five of
      102 patients received CT every 3 weeks using cisplatin 75 mg/m2 i.v. day 1 plus
      cyclophosphamide 750 mg/m2 i.v. day 1 (CP, Group A, n = 29), cisplatin 75 mg/m2
      i.v. day 1, plus adriamycin 40 mg/m2 i.v. day 1 and cyclophosphamide (CAP, Group
      B, n = 22) and paclitaxel 135 mg/m2 i.v. day 1 plus cisplatin 75 mg/m2 i.v. day 1
      (TP, Group C, n = 14). Twelve patients received single agent CT and were not
      analyzed. Remaining 25 patients refused CT treatment and were followed for
      survival. RESULTS: The overall response rate (complete and partial) was 59.2% for
      patients receiving CP (Group A), 45% for CAP (Group B) and 76.9% for those
      receiving TP (Group C), p = ns. Response rate was significantly higher for
      patients with platinum sensitive disease compared to those with platinum
      resistant disease; 55.76 vs 39%, p < 0.007. CT was generally tolerated well; 2
      patients died of CT toxicity, one each in Group A (CP) and C (TP), respectively.
      The median survival from the date of relapse for patients receiving chemotherapy
      was 15 months compared to 4 months for those who did not receive chemotherapy, p
      < 0.001. Chemotherapy responders had a significantly higher median survival than
      chemotherapy non-responders, 24 months vs 10 months, p < 0.01. The median overall
      survival was not significantly different in the 3 groups; Group A--15 months,
      Group B--12 months and 15 months in Group C, p = 0.738. On univariate analysis-
      time since last CT (< 6 months vs > 6 months, p < 0.037, response to previous CT,
      p < 0.0183, cisplatinum sensitivity vs resistance, p < 0.032, number of sites (<
      2 vs > 2) of recurrence, p < 0.004 and response to salvage CT, p < 0.01 were
      associated with survival benefit. On multivariate analysis, 2 factors--platinum
      sensitivity and response to salvage CT attained significance. CONCLUSIONS: Our
      study confirms the benefit of platinum based chemotherapy in recurrent EOC.
      Patients with platinum sensitive disease, and those responding to salvage
      chemotherapy benefit most.

PMID- 10932986
TI  - Prenatal diagnosis of severe tricuspid insufficiency in Ebstein's anomaly with
      pulmonary atresia and intact ventricular septum: a case report.
AB  - Pulmonary atresia with intact ventricular septum is an uncommon congenital
      cardiac anomaly which very often present varying degrees of downward displacement
      and dysplasia of the tricuspid valve. A 23-year-old woman was referred at 23
      weeks' gestation because of fetal cardiomegaly detected by routine
      ultrasonography. Ebstein's anomaly with pulmonary atresia was diagnosed by fetal
      echocardiography. On pulsed Doppler examination, a severe tricuspid regurgitation
      was detected. Pulmonary atresia was suspected, as forward flow was not detected
      into pulmonary artery. The fetus was terminated at 25 weeks. At the postmorterm
      examination Ebstein's anomaly with pulmonary atresia and intact ventricular
      septum were confirmed. The finding of right atrial enlargement on an early
      sonogram should prompt the search for tricuspid valve abnormalities with
      tricuspid regurgitation and the presence or development of pulmonary atresia or
      stenosis. With the information provided, early detection of tricuspid valve
      disease should be possible so that the option of therapeutic abortion can be
      offered.

PMID- 10932988
TI  - Distance education: how far can we go?

PMID- 10932987
TI  - Immature brain injury via peroxynitrite production induced by inducible nitric
      oxide synthase after hypoxia-ischemia in rats.
AB  - OBJECTIVE: To determine whether, and if so how, iNOS expresses and affects brain
      injury induced by hypoxia-ischemia in an immature brain. MATERIAL AND METHODS:
      Seven-day-old Wistar rat pups were exposed to right common carotid artery
      ligation followed by 1.5 hours of hypoxia. The time course of iNOS mRNA
      expression, enzymatic activity, and protein production in the cerebral cortex
      were determined. The extent of the infarct area in the cerebral cortex and the
      production of 3-nitrotyrosine (a biomarker of peroxynitrite) were compared
      between the control pups and pups treated with S-methyl-isothiourea (a selective
      iNOS inhibitor). RESULTS: In the cortex ipsilateral to carotid ligation, iNOS
      mRNA appeared from 6 hours to 24 hours after hypoxia-ischemia and disappeared at
      48 hours. The iNOS protein and its activity also increased at 12 hours and
      reached a maximum level at 48 hours after the insult. The percentage of damage in
      the cerebral cortex was significantly higher in the control pups than in treated
      pups (31.9 vs 10.6%). Tri-nitrotyrosine following iNOS expression-positive cells
      were located predominantly at the infarct and peri-infarct regions. CONCLUSIONS:
      iNOS expression might be an important determinant of ischemic immature brain
      injury.

PMID- 10932989
TI  - Making the case for a college-run case management practice.

PMID- 10932990
TI  - Acculturation and accommodation in qualitative and quantitative research.

PMID- 10932991
TI  - Nurse executive. Make the glue red.

PMID- 10932992
TI  - Public policy. An opportunity to revisit the issues.

PMID- 10932993
TI  - Current strengths and limitations of doctoral education in nursing: are we
      prepared for the future?
AB  - The number of doctoral programs in nursing has increased significantly over the
      past 20 years. This growth has been driven in part by the pressing need to supply
      faculty to teach in undergraduate and graduate programs in nursing. Yet,
      enrollment in and graduation from these programs has remained fairly constant
      even as the number of programs has grown. During this 20-year period, there have
      been numerous conferences, workshops, and meetings devoted to the topic of
      doctoral education with a constant thread running through them calling for the
      need to maintain quality--quality students, quality faculty, quality research,
      and quality course work and requirements--in them. Faculty teaching in these
      programs have given considerable thought to ways of assuring quality in the
      program of study so as to ensure the graduate's ability to function as a teacher
      and researcher. Yet, despite these efforts, still less than 50 per cent of
      nursing faculty possess the doctorate, faculty are experiencing difficulty in
      fulfilling the tripartite mission of colleges and universities, and extramural
      funding for research is very unevenly distributed across programs and, in total,
      is inadequate to build the science. This article examines the strengths and
      weaknesses of doctoral programs in nursing at the start of the new millennium in
      which the challenges in higher education are forecasted to become more focused
      and intense, using accepted benchmarks of quality for students, faculty, and
      curricula.

PMID- 10932994
TI  - Responsibility-centered management: a 10-year nursing assessment.
AB  - In 1988-89, Indiana University became the first public university to implement
      responsibility-centered management (RCM) comprehensively. This article describes
      and assesses the implementation of RCM on the core campus of Indiana University
      School of Nursing in Indianapolis. It describes how RCM encouraged an information
      rich environment, particularly with the advent of economic modeling; decision
      making linked to strategic goals/objectives; and a performance-based reward
      structure (e.g., merit pay increases and incentive plans). It ends with a
      discussion about the worth of RCM and the changes that frame-work produced,
      particularly in reconceptualizing the roles of the business officer and dean. The
      most profound consequence of RCM may be the effect it has in encouraging
      rethinking of what it means to be a school of nursing at this point in time.

PMID- 10932995
TI  - Specialist nurses in Australia: the ICN and international regulation.
AB  - This article focuses on the relationship between specialist nurses in Victoria
      (Australia) and the International Council of Nurses (ICN). A major consideration
      is whether international standards can be applied across international
      boundaries. The ICN has represented the worldwide nursing community for the past
      100 years. In 1997 the Royal College of Nursing (Australia) gained membership to
      the ICN and to its Regulation Network. With growing interest about
      internationalization, a key question is whether Australian nurses will accept the
      Council recommendations on regulation. In a report on specialist nurse education
      in Australia, recommendations were made that included the adoption of the ICN
      definition for specialist practice. A survey of the opinions of 75 nurses
      practicing in Victoria, toward a selection of recommendations from the report,
      showed strong agreement on definition and much less agreement on minimum
      credentials. Findings from the survey are discussed in relation to the
      international profile that is now expected of specialist nurses in Australia and
      a potential future role for professional organizations.

PMID- 10932996
TI  - Student-faculty joint authorship: ethical and legal concerns.
AB  - Although faculty mentoring through joint authorship with students offers benefits
      to both, the claim of joint authorship of students' works by faculty members may
      raise ethical and legal concerns. Whether based on institutional policies,
      faculty members' mandates or suggestions, or even students' invitations, such
      claims may violate principles of autonomy, fidelity, veracity, and justice.
      Moreover, such claims may be contrary to basic requirements of copyright law
      relating to joint authorship and derivative works. Unjustified claims to
      authorship may have adverse effects on the student-faculty relationship, give
      rise to professional embarrassment for the individual faculty and the
      institution, or lead to legal liability. The responsibility to address ethical
      and legal concerns inherent in such joint authorship rests with the
      administration and faculty of the individual nursing education department.

PMID- 10932997
TI  - Nurses' lived experience of being a preceptor.
AB  - Registered nurses' lived experience of preceptorship was studied in this
      phenomenological study. To illuminate the meaning of registered nurses'
      experience of being a preceptor for student nurses, individual tape-recorded
      interviews were conducted with 17 registered nurses. They narrated their
      experience of being a personal preceptor for student nurses during practical
      training on a hospital unit, and the interviews transcribed verbatim were
      analyzed phenomenological-hermeneutically. The analysis revealed two main themes
      (1) including the student in their daily work and (2) increasing awareness of the
      process of learning, as well as six other themes, which contributed to a new
      comprehension of the meaning of being a preceptor. All the themes were related to
      the ongoing preceptor-preceptee relationship. The preceptors' thinking on past
      experiences and their ideas of nursing care in the future were present
      simultaneously. Nurses acting as preceptors were perceived as conscious
      individuals, demanding a balance of their daily work responsibility with
      increased awareness of the professional demands of nursing care. Preceptors
      gained increased awareness of and a desire to fulfill the student nurses' varied
      learning needs and increased awareness of their own learning process.

PMID- 10932999
TI  - American healthcare scene is changing rapidly.

PMID- 10932998
TI  - A collaborative research utilization approach to evaluate the effects of pain
      management standards on patient outcomes.
AB  - The generation of research-based knowledge is incomplete unless it reaches
      clinicians at the point of care. Despite major advances in clinical research
      related to pain management, inadequate pain relief has become a significant
      quality issue in hospitalized patients, which has created an imperative for
      research-based pain management. Using a collaborative research utilization model,
      multidisciplinary academic scientists were paired with clinicians and
      undergraduate and graduate students to form a partnership that (1) examined the
      research base in pain management, (2) generated a research-based standard for
      pain management, and (3) evaluated the effect of that standard on four patient
      outcome variables in a 230-bed teaching hospital. A 2-group, pretest-intervention
      posttest, quasi-experimental clinical trial composed of 173 surgical and oncology
      subjects was conducted. Subjects whose caregiver used the new standard had less
      pain during their hospital stay, less interference by pain with quality-of-life
      indicators, and greater satisfaction with the interventions used as well as
      caregiver responsiveness to their pain. Interestingly, each of these improvements
      decreased after their discharge home. These results strongly suggest the need for
      better postdischarge preparation for pain management and for further development
      and testing of pain management standards in postdischarge settings. They also
      provide the basis for extending the model to address other situations in which
      there is a lag between the promising results of empirical research and their
      integration into practice.

PMID- 10933000
TI  - Violence and nursing.

PMID- 10933002
TI  - A critical review of the literature on foot orthoses.
AB  - Many reports have been published on the value of foot orthoses in treating a
      variety of biomechanical problems. This article reports on the application of
      rules developed in the 1980s to assess the scientific rigor, and hence the
      clinical applicability, of these publications.

PMID- 10933001
TI  - Velocity of the center of pressure during walking.
AB  - The purpose of this study was to describe the velocity of the center of pressure
      during walking in a sample of young, healthy individuals. The velocity of the
      center of pressure was recorded in 60 subjects while they walked barefoot over a
      floor-mounted pressure platform. The results of this study indicate that the
      velocity of the center of pressure follows a predictable pattern during the
      stance phase of walking. Intraclass correlation coefficients calculated to
      measure between-trial reliability for specific parameters of the velocity of the
      center of pressure ranged from 0.361 to 0.912. These study results suggest that
      velocity of the center of pressure may be a useful measurement in future gait
      research.

PMID- 10933003
TI  - The normal foot.
AB  - The term "normal foot" has many different interpretations. This article reviews
      some of the ways in which the word "normal" has been used historically to
      describe the foot. Also discussed are the problems of attempting to determine
      what should constitute a normal foot and proposed criteria for distinguishing
      between the normal and the pathological.

PMID- 10933004
TI  - Effectiveness of various materials in reducing plantar shear forces. A pilot
      study.
AB  - Vertical plantar forces are known to be a major precipitating factor in the
      development of foot pathology. It is also postulated that shear forces are
      important in the pathogenesis of foot ulcers in patients with diabetes mellitus.
      Various materials are used in insoles designed to reduce forces on the foot.
      While many foam materials have been tested for their ability to dissipate
      vertical forces, few studies have tested the effect of these materials on shear
      forces. This study assessed the effectiveness of five different materials in
      reducing plantar shear forces and compared two new gel materials with three of
      the more conventional foam materials. Four subjects were tested while walking
      over a force platform with one of the five materials taped to the surface. Peak
      force, impulse, and resultant shear force data were analyzed. The gel materials
      were significantly better than the foam materials at reducing shear forces. Thus
      the use of gel materials in insoles may be indicated for the reduction of plantar
      shear forces on the diabetic foot.

PMID- 10933005
TI  - The biomechanics, etiology, and treatment of cycling injuries.
AB  - The authors review the biomechanics of cycling and discuss the ideal cyclist's
      morphology. Examination of the cyclist when resting and when cycling is
      described. A variety of overuse injuries commonly sustained by cyclists are
      reviewed, and strategies for altering the cyclist's mechanics to relieve the pain
      are described. Because the bicycle and the cyclist must be considered as a unit,
      this article offers instruction for adjusting the bicycle as well as the cyclist.

PMID- 10933006
TI  - The role of theory in understanding the midtarsal joint.

PMID- 10933007
TI  - Cryptococcal arthritis in an immunocompetent host.
AB  - Cryptococcus neoformans is an opportunistic pathogen that occasionally causes
      indolent disease in the immunocompetent. Cryptococcal arthritis is especially
      rare, and diagnosis is typically delayed. Fungal arthritis should be considered
      in cases of chronic, indolent joint inflammation. To our knowledge, this report
      documents the first use of fluconazole for treatment of cryptococcal infection
      confined to a joint.

PMID- 10933008
TI  - The medicinal potential of blueberries. A new nutraceutical for South Carolina
      farmers.

PMID- 10933009
TI  - Diminished medical morale syndrome. A profession's impairment.

PMID- 10933010
TI  - How medicine lost its way: perspectives of two physicians--grandfather and
      granddaughter.

PMID- 10933011
TI  - Long-term results of laser in situ keratomileusis for high myopia.
AB  - The objective of this study was to evaluate the results of laser in situ
      keratomileusis (LASIK) for high myopia after a follow-up of two years. A total of
      42 eyes from 33 patients with high myopia (range: -9.00 D to -25.50 D) were
      studied. LASIK was performed using an automated microkeratome (Steinway, USA) and
      OmniMed II excimer laser with the standard MKM program (Summit Technology, Inc.,
      Waltham, MA) in all patients. The patients were followed up at one, three, six,
      12 and 24 months. During follow-up manifest refraction and best corrected and
      uncorrected visual acuity were measured. Any complications were also analyzed.
      The two-year follow-up results were as follows. The mean postoperative manifest
      spherical equivalents (MSE) were -0.51 D at one month, -1.09 D at three months, 
      1.78 D at six months, -2.17 D at 12 months and -2.61 D at 24 months. Myopic
      regression continued during the two-year follow-up (p < 0.05). The accuracy of
      the intended postoperative correction within +/- 2.00 D was 73.8% at one month,
      69.1% at three months, 52.4% at six months, 52.4% at 12 months, and 45.2% at 24
      months. The best corrected visual acuity (BCVA) was unchanged or increased in 35
      eyes (83.3%). Only three eyes (7.2%) lost two or more lines of BCVA. This was due
      to irregular astigmatism in one eye, macular degeneration in one eye, and
      rhegmatogenous retinal detachment in one eye. In this study, LASIK was effective
      and safe in the correction of high myopia, however continuous myopic regression
      was seen over the two-year follow-up. Refining the nomogram to adjust for
      progressive myopic regression will be necessary in order to obtain better
      results.

PMID- 10933012
TI  - Corneal flap dimensions in laser in situ keratomileusis using the Innovatome
      automatic microkeratome.
AB  - To evaluate the thickness and size consistency of the corneal flap created with
      the Innovatome automatic microkeratome and to determine any correlation between
      preoperative variables and these corneal flap dimensions, we performed a
      prospective study comprising of 268 eyes of 143 patients having laser in situ
      keratomileusis. Either No. 170 or No. 190 blade was used, and preoperative
      variables including the central corneal thickness, keratometry (K) reading,
      spherical equivalent, and the blade type were measured. The mean central corneal
      flap thickness was 138.8 +/- 23.5 microns (range, 71.6-193.7 microns) in blade
      170 group, and 148.3 +/- 25.4 microns (range, 80.3-211.7 microns) in blade 190
      group. No relationship was found between the corneal flap thickness and the
      preoperative K reading or the spherical equivalent, but the corneal flap
      thickness increased with the preoperative central corneal thickness. The mean
      vertical flap diameter was 9.18 +/- 0.25 mm (range, 8.50-9.75 mm) in blade 170
      group, and 9.50 +/- 0.31 mm (range, 8.75-10.00 mm) in blade 190 group. No
      relationship was found between the corneal flap diameter and the preoperative
      central corneal thickness or the spherical equivalent, but the corneal flap size
      increased with the preoperative K reading.

PMID- 10933013
TI  - Stimulation of macrophage function by S-antigen: production of nitric oxide.
AB  - In this study, we investigated whether retinal soluble proteins, such as S
      antigen, play a role in the induction of nitric oxide by macrophages in vitro.
      Cells from the murine macrophage cell line RAW 264.7 and rat and rabbit
      peritoneal macrophages were incubated in the presence of retinal soluble protein.
      The nitrite level in the cultured supernatant was measured to determine nitric
      oxide production using the Griess reaction. S-antigen induced significant, dose
      dependent nitrite production in both RAW 264.7 and rat peritoneal macrophages.
      The induction of inducible nitric oxide synthase by retinal protein was inhibited
      by the iNOS-specific inhibitor, aminoguanidine and the tyrosine inhibitor,
      genistein. These results show that soluble retinal protein significantly induces
      nitric acid production by macrophages. Increased production of reactive oxygen
      species by macrophages in the presence of this soluble retinal protein in vivo
      may accelerate photoreceptor degeneration in uveitis.

PMID- 10933014
TI  - Long-term visual recovery after scleral buckling procedure of rhegmatogenous
      retinal detachment involving the macula.
AB  - The long-term visual recovery after a scleral buckling procedure for
      rhegmatogenous retinal detachment involving the macula was investigated
      retrospectively. The patients had been treated with a segmental or encircling
      scleral buckle procedure and in this study the follow-up period was between 5 and
      11 years. In order to investigate the natural course of functional recovery of
      the reattached retina, all cases with a history of intraocular surgery or trauma
      were excluded. In this investigation, 34 patients were selected in which 35 eyes
      were studied. The best corrected visual acuities between a 6-month and 5-year
      postoperative period were compared. They were found to be more improved 5 years
      after surgery than after 6-month by two or more lines in 19 eyes (54%). In these
      19 eyes, the visual acuities continued to improve up to 10 years after surgery.
      Improvement in the long-term postoperative visual acuity was found to correlate
      with the shorter duration of macular detachment (30 days), zero or mild myopia (
      6 diopters) and to a lesser extent, retinal detachment. the visual function of
      the reattached human retinas may continue to improve over the long term,
      especially when these beneficial factors are present.

PMID- 10933015
TI  - Effect of IOP elevation on matrix metalloproteinase-2 in rabbit anterior chamber.
AB  - To investigate changes in the level of matrix metalloproteinase-2 (MMP-2) in the
      anterior chamber of rabbit with intraocular pressure (IOP) elevation. The IOP was
      elevated with scleral encircling in 12 rabbits. In the control group (4 rabbits),
      IOP was not changed after scleral encircling, and in group 1 (4 rabbits) and 2 (4
      rabbits), IOP was elevated about 10 and 20 mmHg respectively after scleral
      encircling. At 2 days after scleral encircling, aqueous sampling was performed
      and levels of MMP-2 were checked by Western blots and gelatin zymograms. The
      greater the IOP elevation, the more MMP-2 expression in the anterior chamber by
      Western blots and gelatin zymograms. The increase in MMP-2 expression in response
      to IOP elevation may have important implications for the IOP feedback control
      mechanism.

PMID- 10933016
TI  - A comparison of Min's glasses and conventional occlusion therapy in the treatment
      of amblyopic children: a prospective study.
AB  - Min's glasses are specially manufactured in order to enhance the satisfaction of
      the wearer and increase treatment effectiveness. We compared the effectiveness of
      Min's glasses with that of conventional occlusion therapy in amblyopic pediatric
      patients. We prospectively studied 60 amblyopic patients. For four to 30 months,
      24 of the patients were treated with conventional patch occlusion (patch group)
      and 36 of them were treated with Min's glasses (glasses group). We compared the
      improvement in visual acuity and the treatment compliance between both groups,
      according to age (over six and less than six), sex, type of amblyopia, and the
      duration of treatment. Sixteen patients (66.7%) in the patch group and 32
      patients (88.9%) in glasses group showed improvement in visual acuity (p =
      0.002). The pre-treatment average log MAR acuity was 0.56 +/- 0.25 in the patch
      group, and 0.59 +/- 0.25 in the glasses group. The average improvement in visual
      acuity was a 0.17 log MAR score in the patch group, and a 0.31 log MAR score in
      the glasses group (p = 0.004). Compliance was 59.54% in the patch group and
      83.44% in the glasses group (p = 0.012). The pre-treatment average log MAR acuity
      was 0.49 +/- 0.23 for children over six years of age in the patch group, and 0.58
      +/- 0.28 for children over six years of age in the glasses group. For children
      over six years of age in the glasses group the improvement in visual acuity (0.29
      log MAR score) was greater than for children over six years of age in the patch
      group (0.06 log MAR score) (p = 0.0003). The pre-treatment average log MAR acuity
      was 0.55 +/- 0.22 for female patients in the patch group, and 0.60 +/- 0.25 for
      female patients in the glasses group. Female patients in the glasses group also
      showed a greater visual acuity improvement (0.29 log MAR score) than female
      patients in the patch group (0.14 log MAR score) (p = 0.0028). However, there
      were no differences between the groups in patients less than six years of age and
      in male patients. In conclusion, Min's glasses were more effective than
      conventional treatment with a patch in improving visual acuity and encouraging
      compliance in pediatric amblyopic patients, especially in children over six years
      of age and in girls.

PMID- 10933017
TI  - Inadvertent topical exposure to isocyanates caused damage to the entire eyeball.
AB  - Isocyanates are part of a group of important chemicals necessary in the
      production of adhesives, synthetic rubbers, and a variety of plastics. They are
      known to have minimal toxic effects when administered locally. However, we
      experienced a case of damage involving the entire eyeball in a person who
      accidentally exposed his eye to isocyanates. The patient presented with inflamed
      conjunctiva, and shrunken cornea and sclera, with focal atrophic changes in the
      iris. The lens and vitreous were opacified. After removal of the lens and
      vitreous, there were large areas of atrophic retina and areas of retinal necrosis
      with holes. We found that locally absorbed isocyanates can cause damage to the
      entire eyeball. Therefore, we recommend that if there is any evidence of
      isocyanate penetration, early vitrectomy should be performed to help in
      determining the extent of retina damage and to decrease the amount of toxic
      substance in the vitreous.

PMID- 10933018
TI  - Massive suprachoroidal hemorrhage with retinal and vitreous incarceration; a
      vitreoretinal surgical approach.
AB  - Suprachoroidal hemorrhage(SH) may cause the expulsion of the intraocular
      contents. Vitreous incarceration in the wound and retinal detachment with SH are
      extremely poor prognostic signs. Treatment modalities depend on the severity of
      eye damage. This particular patient had "kissing" hemorrhagic choroidal
      detachment which completely filled the vitreous cavity after cataract surgery. It
      seemed to be inoperable. Secondary surgery was delayed 3 days to lower IOP to
      normal levels. The eye underwent anterior drainage sclerotomy under constantly
      maintained limbal or pars plana infusion fluid line pressure. The authors
      performed a pars plana vitrectomy, followed by perfluorocarbon liquid injection
      and a silicone oil tamponade. After this surgical approach, the patient attained
      an attached retina and a visual acuity of 5/200 at the 3 month follow-up.

PMID- 10933019
TI  - A family with Leber's hereditary optic neuropathy with mitochondrial 11778/ND4
      and 4216/ND1 mutations.
AB  - Leber's hereditary optic neuropathy (LHON) is caused by a point mutation in the
      mitochondrial deoxynucleic acid (mtDNA) and accounts for 30% of bilateral optic
      atrophy of unknown etiology. The authors found a Korean family with mtDNA
      mutations in the nucleotide positions (np) 11778 and np 4216. This is the first
      report confirming a secondary mtDNA np 4216 mutation in Koreans, as well as the
      first report of a Korean family harboring both primary and the secondary
      mutations that the authors are aware of.

PMID- 10933020
TI  - Optic neuritis after bee sting.
AB  - The purpose of this report is to document an unusual case of fully recovered
      vision after optic neuritis caused by bee sting. A 46-year-old man presented with
      sudden visual loss after being stung by a bee on the left conjunctiva. He
      developed optic disc swelling and there was a delay in the P100 wave of the
      pattern visual evoked potential (VEP). The patient received acute treatment, with
      intravenous methylprednisolone followed by oral prednisolone. Two days later,
      visual acuity in the left eye was recovered to 20/20 and P100 latency in pattern
      VEP was also normalized. Furthermore, visual field and color vision tests
      revealed no remaining abnormalities. This case suggests that early corticosteroid
      treatment is effective in optic neuritis caused by bee sting.

PMID- 10933021
TI  - [Pretreatment of acid-induced lung injury with specific neutrophil elastase
      inhibitor ONO-5046 did not exasperate the subsequent bacterial lung infection by
      Pseudomonas aeruginosa].
AB  - Patients with acid lung injuries are at high risk for bacterial pulmonary
      infections which commonly occur several days after the acid aspiration. We
      reported that a specific neutrophil elastase inhibitor ONO-5046 inhibited the
      multi-organ injury caused by acid-instillation into the lung. In this study, we
      evaluated the effect of ONO-5046 on lung infection by Pseudomonas aeruginosa (PAO
      1:Ps.) following acid-induced lung injury in rat lungs. Animals received 0.2 ml
      of hydrochloric acid (pH = 1) into the right lungs. Pretreated animals were
      administered ONO-5046 (30 mg.kg-1) i.v. 15 min. before acid instillation. Other
      groups received vehicle (saline). Twenty four hours later, they were instilled
      with 0.1 ml of Ps. 1 x 10(8) cfu into the left lungs. Four hours after bacterial
      challenge, the animals were deeply anesthetized and killed. Bronchoalveolar
      lavage was done on each lung separately to evaluate neutrophil elastase activity,
      neutrophil number and protein permeability of lung endothelium and epithelium.
      The numbers of Ps. in the lungs were measured. In the Ps.-instilled lung, the
      number of Ps. or the protein permeability was not increased with ONO-5046
      pretreatment compared with those in the untreated group. Pretreatment inhibited
      the exasperation of the protein permeability indirectly caused by Ps. infection
      in the acid-instilled lung. It was indicated that ONO-5046 could inhibit the
      indirect lung injury caused by acid-instillation into the lung without
      aggravating the subsequent bacterial infection.

PMID- 10933023
TI  - [A comparison of bullard laryngoscope and intubating laryngeal mask using
      fiberoptic guidance for tracheal intubation].
AB  - The purpose of this study is to compare the success rate of tracheal intubation,
      intubation time and laryngoscopic view of the larynx by Bullard laryngoscope or
      by intubating laryngeal mask using fiberoptic guidance in 50 patients. Following
      a standardized induction protocol, conventional laryngoscopic view by Macintosh's
      laryngoscope was obtained and classified by Cormack's grades. We measured the
      times from incertion of laryngoscopy or laryngeal mask until obtaining the best
      view of the larynx and until tracheal intubation. A best view by Bullard
      laryngoscopy or by fiberoscopy through the laryngeal mask was classified by
      Cormack's grades. The success rate of tracheal intubation was higher by Bullard
      laryngoscopy than by intubating laryngeal mask. The durations of laryngoscopy and
      tracheal intubation were significantly shorter and Cormack's grades were
      significantly lower by Bullard laryngoscopy than by laryngeal mask and
      fiberscopy. These results demonstrate that tracheal intubation by Bullard
      laryngoscope is faster and more successful compared with intubating laryngeal
      mask using fiberoptic guidance.

PMID- 10933022
TI  - [Target-controlled propofol infusion for general anesthesia in three obese
      patients].
AB  - We report three cases in which the target-controlled propofol infusion technique
      was used in obese patients for general anesthesia. General anesthesia was induced
      by intravenous administration of fentanyl 150-300 micrograms and ketamine 50-80
      mg and propofol 2 micrograms.ml-1 to achieve a target blood concentration by
      target-controlled infusion system. Anesthetic maintenance was achieved by
      ketamine 1 mg.kg-1.h-1 for 1 hour after the induction, propofol at target blood
      concentration of 2-3.5 micrograms.ml-1 and the intermittent epidural injection of
      1.5% lidocaine through an epidural catheter. The surgical procedures were
      uneventful. The estimated blood concentrations of propofol at emergence from
      anesthesia calculated by ConGrace ranged from 1.49-1.69 micrograms.ml-1, and it
      took 230-300 seconds to emerge from anesthesia. The target-controlled propofol
      infusion technique appears useful to control the depth of anesthesia in obese
      patients.

PMID- 10933024
TI  - [A new sedation technique with propofol during spinal anesthesia].
AB  - We compared our new sedation technique with propofol during spinal anesthesia
      (Group B, n = 50) with a previously described method by Mackenzie et al. (Group
      A, n = 20). In Group A, propofol was started at a rate of 6 mg.kg-1.h-1 for 10
      minutes, followed by continuous infusion at a rate of 4 mg.kg-1.h-1 till the end
      of surgery. In Group B, propofol 0.4 mg.kg-1 was administered by a bolus
      injection at the beginning. One-hundred and fifty minutes after the first
      injection, propofol 0.2 mg.kg-1 was added. The third dose of 0.1 mg.kg-1 of
      propofol was given 150 seconds after the second dose, followed by continuous
      infusion at a rate of 4 mg.kg-1.h-1 till the end of surgery. When adequate
      sedation was not obtained in Group B, propofol 0.1 mg.kg-1 was added by bolus
      fashion occasionally. In Group A, it took 9 min. 29 sec. to complete adequate
      sedation assessed by Mackenzie and Grant's sedation score. On the other hand, in
      Group B, it was 7 min. 27 sec. (P < 0.05 compared with Group A). There was
      neither excitation nor movement during sedation in Group B, while 5 patients
      experienced such events in Group A. The blood concentrations of propofol in Group
      B was 0.946 +/- 0.076 microgram.ml-1 and 0.693 +/- 0.136 microgram.ml-1 at 5
      minutes and 10 minutes after the beginning of propofol, respectively. These
      values were significantly lower than those reported by Kugimiya. Our newly
      developed method for sedation with propofol during spinal anesthesia would be
      safer and more effective than that previously described by Mackenzie et al.

PMID- 10933025
TI  - [A comparison of fentanyl and buprenorphine in total intravenous anesthesia using
      propofol during spinal surgery].
AB  - A retrospective study was performed to compare the hemodynamic effect and
      postoperative pain relief of fentanyl (Group F, n = 11) and buprenorphine (Group
      B, n = 11) in total intravenous anesthesia (TIVA) using propofol during spinal
      surgery. All patients were premedicated with midazolam (3-5 mg) i.m. Anesthesia
      was maintained with propofol infusion, and increments of fentanyl or single dose
      of buprenorphine with 40% oxygen in air. Total doses of fentanyl and
      buprenorphine were 7.6 +/- 1.0 micrograms.kg-1 and 2.0 +/- 0.4 micrograms.kg-1,
      respectively. Maintenance doses of propofol (Group F: 5.5 +/- 0.8 mg.kg-1.h-1,
      Group B: 5.9 +/- 1.1 mg.kg-1.h-1) and vecuronium were not significantly
      different. Mean arterial pressures from 2 hours after incision to the end of
      surgery were elevated significantly in Group F than in Group B. Recovery time
      (Group F 12.5 +/- 6.1 min vs Group B 11.8 +/- 6.1 min) and extubation time (Group
      F 19.5 +/- 10.3 min vs Group B 15.0 +/- 7.0 min) were not different. At the end
      of anesthesia, seven patients in Group F and one patient in Group B (P < 0.01)
      complained of severe pain. All patients in Group F, and only two in Group B (P <
      0.02) received analgesics within 20 hours. Neither nausea nor respiratory
      depression was found in both groups. This study suggests that buprenorphine would
      provide a more stable hemodynamic state and better postoperative pain relief than
      fentanyl in TIVA using propofol.

PMID- 10933026
TI  - [Anesthetic management for neonates with congenital cystic adenomatoid
      malformation].
AB  - We experienced two cases of congenital cystic adenomatoid malformation (CCAM)
      diagnosed by prenatal ultrasonography. The first case with type I CCAM underwent
      the resection of the right upper lobe 8 days after birth. Postoperative course
      was uneventful. The second case with type III CCAM developed non-immune hydrops,
      severe mediastinal shift, and polyhydroamnios at 29 weeks' gestation. At 30
      weeks' gestation, cesarean section was performed. Immediately after birth, the
      resection of lung tumor for the neonate was performed. However, the neonate died
      on the 1st postoperative day.

PMID- 10933027
TI  - [Cesarean section in a pregnant patient with placenta percreta involving the
      urinary bladder].
AB  - Placenta percreta involving adjacent structures is serious complication of
      pregnancy with a high mortality rate. A 32-year-old woman, gravida 4, para 3, who
      had previously undergone a cesarean section, was admitted to our hospital at 31
      weeks' gestation for placenta previa. At 33 weeks' gestation, the diagnosis of
      placenta percreta with involvement of the urinary bladder was made by
      ultrasonography and magnetic resonance imaging. At 34 weeks' gestation, an
      elective cesarean section was scheduled. Anesthesia was maintained with
      sevoflurane in oxygen before delivery, and with nitrous oxide in oxygen, fentanyl
      and midazolam after delivery. During the operation, attempts to remove the
      placenta resulted in massive hemorrhage. Blood loss for the procedure was 13,800
      g. Because of the extreme hemorrhage, we encountered hemorrhagic shock and
      postoperative complications despite the preoperative preparation. In case of
      placenta percreta, it is essential to prepare adequate volume of blood for
      transfusion at the start of surgery and secure large bore intravenous lines. A
      rapid transfusion device may be recommended. Regarding the anesthetic management,
      general anesthesia is preferable in consideration of the risk of hemorrhagic
      shock and the length of operation time. Furthermore, we need team approach and
      preoperative management to prevent the uncontrolled hemorrhage in such a severe
      case.

PMID- 10933028
TI  - [A case of drug allergy to hydroxyzine used for premedication].
AB  - A 37-year-old woman, scheduled for total knee replacement, complained of nausea
      and abdominal pain 30 min after pre-medication with intramuscular atropine and
      hydroxyzine. Hypoxemia and skin eruption all over her body was noticed in the
      operating room. Although hemodynamic changes were not observed, the operation was
      postponed. LST (lymphocyte stimulation test) showed the positive response with
      hydroxyzine but negative with atropine and antibiotics. This result suggests that
      hypersensitivity was caused by hydroxyzine in this patient.

PMID- 10933029
TI  - [Damage of a laryngeal mask airway during anesthesia].
AB  - A 21-year-old man was scheduled for fixation of a fractured radius and ulna under
      general anesthesia using a laryngeal mask airway (LM). Anesthesia was induced
      with propofol 120 mg and fentanyl 0.1 mg. After administration of vecuronium 6
      mg, we attempted insertion of the LM (# 5). The first trial was unsuccessful
      because the tube of the LM was bent in the pharynx. We attempted it again and the
      LM was successfully inserted. It was connected with the anesthetic circuit, and
      manual ventilation was started. However, the LM was suddenly broken at the basal
      part of the tube connector before the start of operation, and it became detached
      from the anesthetic circuit. Therefore, we removed the remaining LM from the
      mouth, and inserted a new LM (# 5). The peroperative course was uneventful. We
      conclude that inspection of a recycled LM is important before using it in order
      to prevent such an event as the present case.

PMID- 10933030
TI  - [Anesthetic management of an extremely low birth weight neonate for two thoracic
      surgeries of patent ductus arterious and coarctation of the aorta].
AB  - An extremely low birth weight (832 g) and 29 gestational week neonate underwent
      surgical ligation of patent ductus arterious 20 days after birth and repair of
      coarctation of the aorta two months after the first operation. She developed
      asphyxia neonatorum and was artificially ventilated because of IRDS and attack of
      apnea. At the first operation, anesthesia was maintained with fentanyl and
      sevoflurane. The only perioperative complication was severe hypothermia (34.5
      degrees C). At the second operation, anesthesia maintenance was identical to the
      first operation. The only perioperative complication was mild hyperthermia (37.7
      degrees C). The key points of anesthetic management were the use of a low
      inspired oxygen fraction to avoid retrolental fibroplasia at a gestational age
      before 32 weeks and management of the baby's temperature.

PMID- 10933031
TI  - [Successful fiberoptic intubation for a patient with lingual tonsillar
      hyperplasia].
AB  - Hypertrophied lingual tonsils are rare, but may cause difficulty or inability in
      tracheal intubation during induction of general anesthesia. A 39-yr-old woman was
      scheduled for resection of symptomatic hypertrophied lingual tonsils. In this
      patient, we examined two methods of oro-tracheal intubation either with rigid
      laryngoscopy or flexible fiberoscopy using trans-nasal fiberopic monitoring.
      Direct laryngoscopy failed to expose the trachea because of large hypertrophied
      tissue, and fiberoscopic intubation was also difficult since a large mass
      hindered acquiring a suitable view. However, transnasal fiberoscopic monitoring
      could guide the orotracheal fiber into the trachea for intubation. When an
      anesthesiologist can predict the abnormality of lingual tonsils, this combination
      might be recommended for difficult airway and intubation.

PMID- 10933032
TI  - [Anesthetic management of a patient with chronic high spinal cord injury (second
      report)].
AB  - We administered anesthesia twice to a 43-year-old male patient with complete
      sensory and motor disturbance below the upper thoracic nerves due to chronic high
      spinal cord injury. The first operation was the gluteus maximus musculocutaneous
      flap for closure of a sacral decubitus ulcer under general anesthesia. The second
      was the transurethral lithotripsy for the bladder stone under spinal anesthesia.
      Severe hypertension occurred probably due to autonomic hyperreflexia (AH) during
      both operations. Therefore, we must be careful in anesthetic management of
      patients with chronic high spinal cord injury, because AH might occur in any
      anesthetic administration.

PMID- 10933033
TI  - [Patent blue-induced false-methemoglobinemia].
AB  - We experienced an anesthetic case, in which interference in oxygen saturation
      values by patent blue was mistaken for nitroglycerin-induced methemoglobinemia. A
      40-year-old woman underwent mastectomy for breast cancer under general
      anesthesia. Nitroglycerin was infused to produce hypotensive anesthesia. Patent
      blue was locally injected around the cancer by a surgeon and surgery was started.
      A few minutes later, oxygen saturation by finger pulse oximeter suddenly
      decreased from 100% to 90%. And then, blood gas analysis was performed to confirm
      this change. The decrease of oxygen saturation and the increase of methemoglobin
      were also observed in the finding of blood gas analysis. At first, we judged
      these changes as methemoglobinemia by nitroglycerin infusion. Finally, however,
      we concluded that all these changes were attributable to the interference by
      patent blue on oxygen saturation value because we found that there had been some
      inconsistent findings as methemoglobinemia. The fact seems that nothing happened
      to the patient during the episode. This case showed us that anesthesiologists
      should understand the principle of hematological monitors and the meaning of the
      data obtained by monitors.

PMID- 10933034
TI  - [Anesthetic management of a patient with latex allergy diagnosed preoperatively].
AB  - Since the first report in 1979, the number of patients with latex allergy has
      progressively increased. We experienced an anesthetic management of a 3 year-old
      child who underwent the repair of anal atresia. The first operation was performed
      in newborn period. After the surgery, the patient developed skin rash and the
      loss of consciousness every time anal irrigation was made with latex-containing
      catheter. Latex-allergy was diagnosed at the age of 3 years, with the positive
      skin test by latex extract. It took enormous time and efforts to find out the
      possibility of latex-contamination in a wide variety of medical equipments and
      supplies to prevent allergic reaction during perioperative period. In this
      patient, perioperative cause was uneventful. It is suggested that preoperative
      preparation is essential and caution should be also paid to prevent allergic
      reaction in daily life.

PMID- 10933035
TI  - [Combined intercostal nerve block and epidural anesthesia in a patient with
      severe aortitis syndrome].
AB  - A 74-year-old woman with aortitis syndrome was scheduled for mastectomy. Her left
      vertebral artery was totally occluded and left carotid arteries, left subclavia
      artery and bilateral common renal arteries were occluded. For anesthesia a
      catheter was inserted into the epidural space between T3 and T4. Lidocaine 80 mg
      (2%, 4 ml) was administered epidurally. Then intercostal nerve block was
      performed with bupivacaine 15 mg (0.5%, 3 ml) at T3 and T4 level. Local
      infiltration of lidocaine 50 mg (1%, 5 ml) was added. During the surgery,
      hemodynamics were stable and no neurological symptom was observed. Epidural
      anesthesia alone might be sufficient for anesthesia if higher concentration of
      local anesthetic was used. However, to avoid hemodynamic change, we used 1%
      lidocaine and added intercostal nerve block. We conclude that combined
      intercostal nerve block and epidural anesthesia was useful for a patient with
      severe aortitis syndrome in oder to monitor consciousness to detect cerebral
      ischemia and to avoid hemodynamic instability.

PMID- 10933036
TI  - [General anesthesia for a patient with Cornelia de Lange syndrome].
AB  - Cornelia de Lange syndrome involves anomalies in cardio-vascular and musculo
      skeletal systems, and mental retardation. In addition, a patient with this
      syndrome shows a peculiar look. A 22-year-old woman with Cornelia de Lange
      syndrome underwent general anesthesia twice. She has a small mouth, thin lips, a
      short neck, short limbs, and stiffness of the neck and some joints associated
      with slight mental retardation. She was scheduled for arthroscopy and then for
      rotational acetabular osteotomy and valgus osteotomy. The maximum distance
      between the upper and lower incisors was 34 mm, when she opened her mouth.
      Anesthesia was induced with sevoflurane increased slowly to 7.0% in oxygen 6
      l.min-1 in both procedures. After the administration of 4% lidocaine 3.5 ml into
      the pharynx, orotracheal intubation was attempted, but was not successful. Then
      blind naso-tracheal intubation was performed successfully under spontaneous
      respiration under sevoflurane-oxygen inhalation. The induction of anesthesia with
      sevoflurane under spontaneous respiration was useful for blind naso-tracheal
      intubation in a case with difficult intubation such as in Cornelia de Lange
      syndrome.

PMID- 10933037
TI  - [Intraoperative autologous blood transfusion was effective in a massive blood
      loss during living-related donor liver transplantation].
AB  - We have experienced massive blood loss (> 80,000 g) during living-related donor
      liver transplantation (LRDLT) of a 14-year old girl with biliary atresia. As
      available homologous blood was not sufficient, we transfused autologous blood
      (13,400 ml) during operation. Although immunosuppressant was administered to the
      patient, severe infection did not occur for 10 days after the operation. Cold
      ischemia time of the graft liver was about 16 hr, but her postoperative liver
      function was well-maintained. The case suggests that intraoperative autologus
      blood transfusion is effective if homologous blood is insufficient during LRDLT.

PMID- 10933038
TI  - [Use of modified infrared aural canal thermometers during cardiac surgery].
AB  - Two kinds of modified infrared aural canal thermometers (Mimippi, Superthermo)
      are currently available in Japan. We therefore evaluated their accuracy and
      precision for clinical use. For the purpose of this investigation, we considered
      accuracy to be the mean difference between the test thermometers and the
      reference thermocouple. Precision was examined from the standard deviation of the
      difference between the test and reference values. We evaluated ten patients for
      cardiopulmonary bypass surgery under mild hypothermia (approximately 32 degrees
      C). Aural canal temperatures were measured in a random order with each infrared
      thermometer, and compared with readings from a thermocouple positioned at the
      contralateral tympanic membrane. Compared with the thermocouple, the Mimippi had
      regression slope 0.87 and correlation coefficient 0.79. In contrast, slope of the
      Superthermo regression was 0.74. The correlation coefficient for the Superthermo
      was 0.71. The accuracy (offset, or bias) was 0.91 degree C with the Mimippi. In
      contrast, it was 1.32 degrees C with the Superthermo. The precision (standard
      deviation) of the Mimippi was 0.65. In contrast, it was 0.73 degree C with the
      Superthermo. We conclude that both thermometers were moderately accurate and
      precise for perioperative use.

PMID- 10933039
TI  - [A multicenter study of cardiac events and anesthetic management of patients with
      ischemic heart diseases for noncardiac surgery--a follow-up report].
AB  - We have conducted a joint research project to investigate the incidence of
      ischemic heart disease in patients for noncardiac surgery and to define the risk
      of perioperative cardiac complications in these patients. From September to
      November 1997 we had 7288 patients scheduled to undergo noncardiac surgery in the
      8 departments of anesthesiology. Of these patients, 228 (3.1%) patients had
      ischemic heart disease, and 30 of them (13.2%) developed perioperative cardiac
      events. Critical cardiac events, including perioperative myocardial ischemia and
      lethal arrhythmia, occurred in 7 of these patients. In our region of Japan, 3-4%
      of surgical patients tend to develop ischemic heart disease and 3.1% of them
      demonstrated severe cardiac complications perioperatively. Compared with United
      States we encounter fewer surgical patients with ischemic heart disease, but the
      risk of developing perioperative cardiac complications in such patients is almost
      the same for both countries.

PMID- 10933040
TI  - [Cracks of polycarbonate three-way stopcock are caused by fat emulsion not by
      propofol].
AB  - We found fine cracks in a three-way stopcock after continuous infusion of
      propofol (Diprivan, Astra-Zeneca, UK). In this paper the possible mechanism was
      investigated. At first we checked various three-way stopcocks of various
      manufactures, such as JMS, Terumo, Nipro and Top. All of them were made with
      polycarbonate. Fine cracks were observed in all stopcocks after 6 hours of liquid
      contact with propofol between the three-way stopcock and male connector. Based on
      the mechanical stretch tests of polycarbonate plastic strips with saline, 10% fat
      emulsion (Intralipid, Otsuka, Japan), or 1% propofol in 10% fat emulsion
      (Diprivan), significantly greater cracks were observed in both fat group and
      propofol group, compared with the saline group. But there was no significant
      difference in cracks between fat and propofol groups. The size of crack increased
      in a time and strength dependent manner. We conclude that the cause of cracks in
      three-way stopcock is fat emulsion as a vehicle of propofol not propofol itself.

PMID- 10933041
TI  - [New study on the history of anesthesiology (2)--who is the first Japanese to
      write a scientific paper for the journal "Anesthesiology"?].
AB  - The beginning of modern anesthesiology in Japan dates back to 1950 when Dr M.
      Saklad of Rhode Island Hospital came to Japan to give his lectures on
      endotracheal anesthesia and related procedures. Since then, many Japanese
      surgeons visited the United States to learn anesthesiology in depth and they
      began to write their papers for foreign journals. According to my survey of the
      journal "Anesthesiology" from Vol 1 (1940) through Vol 21 (1960), I found 12
      scientific papers written by Japanese. The first paper by Japanese appeared in
      this journal published in 1955 entitled as "Observations on the action of
      thiopental (Pentothal) on the laryngeal reflex" by Akira Horita et al. He was
      born in the United States in 1928 as a son of Japanese immigrants. He was
      graduated from the University of Washington at Seattle to become professor or
      pharmacology. The first paper based on studies performed in Japan by Japanese
      authors appeared in 1956. It was entitled as "The spread of drugs used for spinal
      anesthesia" by Kitahara et al. This paper is the English translation of their
      Japanese paper which appeared in Nippon Rinsho Geka Ikai Zasshi entitled as
      "Basic Study on Spinal Anesthesia in 1953".

PMID- 10933042
TI  - The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer
      progression.
AB  - As the process of tumor progression proceeds from the normal cellular state to a
      preneoplastic condition and finally to the fully invasive form, the molecular
      characteristics of the cell change as well. These characteristics can be
      considered a molecular fingerprint of the cell at each stage of progression and,
      analogous to fingerprinting a criminal, can be used as markers of the progression
      process. Based on this premise, the Cancer Genome Anatomy Project was initiated
      with the broad goal of determining the comprehensive molecular characterization
      of normal, premalignant, and malignant tumor cells, thus making a reality the
      identification of all major cellular mechanisms leading to tumor initiation and
      progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997). "New
      opportunities for uncovering the molecular basis of cancer." Nat. Genet., 16: 415
      516.], www.ncbi.nlm.nih.gov/ncicgap/). The expectation of determining the genetic
      fingerprints of cancer progression will allow for 1) correlation of disease
      progression with therapeutic outcome; 2) improved evaluation of disease
      treatment; 3) stimulation of novel approaches to prevention, detection, and
      therapy; and 4) enhanced diagnostic tools for clinical applications. Whereas
      acquiring the comprehensive molecular analysis of cancer progression may take
      years, results from initial, short-term goals are currently being realized and
      are proving very fruitful.

PMID- 10933043
TI  - Allogeneic astrocytoma in immune competent dogs.
AB  - We have induced in canines long-term immune tolerance to an allogeneic cell line
      derived from a spontaneous canine astrocytoma. Allogeneic astrocytoma cells were
      implanted endoscopically into the subcutaneous space of fetal dogs before the
      onset of immune competency (< 40th gestational day). At adulthood, dogs rendered
      tolerant successfully serve as recipients of intracranial transplants of their
      growing allogeneic, subcutaneous tumor. Transplanted dogs subsequently develop a
      solid brain tumor with histological features similar to the original astrocytoma.
      This model may allow rapid development and evaluation of new therapies for brain
      tumors, as well as afford tumor biology studies that are untenable in smaller,
      immune incompetent, or inbred animals harboring less representative tumors.

PMID- 10933044
TI  - Early increases in breast tumor xenograft water mobility in response to
      paclitaxel therapy detected by non-invasive diffusion magnetic resonance imaging.
AB  - An important goal in cancer chemotherapy is to sensitively and quantitatively
      monitor the response of individual patients' tumors to successful, or
      unsuccessful, therapy so that regimens can be altered iteratively. Currently,
      tumor response is monitored by frank changes in tumor morphology, yet these
      markers take long to manifest and are not quantitative. Recent studies suggest
      that the apparent diffusion coefficient of water (ADCw), measured noninvasively
      with magnetic resonance imaging, is sensitively and reliably increased in
      response to successful CTx. In the present study, we investigate the combination
      chemotherapy response of human breast cancer tumor xenografts sensitive or
      resistant to Paclitaxel by monitoring changes in the ADCw. Our results indicate
      that there is a clear, substantial, and early increase in the ADCw after
      successful therapy in drug sensitive tumors and that there is no change in the
      ADCw in p-glycoprotein-positive tumors, which are resistant to Paclitaxel. The
      mechanism underlying these changes is unknown yet is consistent with apoptotic
      cell shrinkage and a concomitant increase in the extracellular water fraction.

PMID- 10933045
TI  - Cyclosporin A reverses chemoresistance in patients with gynecologic malignancies.
AB  - Multidrug resistance is a major obstacle in successful systemic therapy of
      gynecologic malignancies. The objectives of this study are to evaluate the
      activity of cyclosporin A used to overcome drug resistance in a variety of
      gynecologic malignancies. Forty women (29 with ovarian cancer, 7 with uterine
      cancer, 3 with cervical cancer, and 1 with choriocarcinoma) were treated with
      cyclosporin A, 4 mg/kg intravenously, 6 hours before and 18 hours after the
      specific chemotherapeutic agent, to which the tumor had developed drug
      resistance. All patients had shown resistance to the chemotherapy agent used in
      combination with cyclosporin A. All patients had been heavily pretreated (mean,
      2.8 previous chemotherapy regimens). Overall, among 38 available patients with
      gynecologic malignancies, a 29% objective response rate was observed. Twenty-six
      (65%) of all patients received three or more cycles of cyclosporin A. There was a
      25% response rate for patients with ovarian cancer patients and 50% for those
      with uterine cancer. There were no responses among the three patients with
      cervical cancer, and the patient with choriocarcinoma had a complete response.
      All patients were evaluable for toxicity. Leukopenia and nausea were the most
      common toxic reactions, but in most cases they were transient, and only three
      patients required a treatment delay. The most common grade 3 or 4 toxicity was
      thrombocytopenia, which was observed in 22% of the patients. Cyclosporin A is
      well tolerated and has significant potential for reversal of chemoresistance in
      heavily pretreated patients with ovarian and uterine malignancies.

PMID- 10933046
TI  - Cancer patient T cells genetically targeted to prostate-specific membrane antigen
      specifically lyse prostate cancer cells and release cytokines in response to
      prostate-specific membrane antigen.
AB  - The expression of immunoglobulin-based artificial receptors in normal T
      lymphocytes provides a means to target lymphocytes to cell surface antigens
      independently of major histocompatibility complex restriction. Such artificial
      receptors have been previously shown to confer antigen-specific tumoricidal
      properties in murine T cells. We constructed a novel zeta chain fusion receptor
      specific for prostate-specific membrane antigen (PSMA) termed Pz-1. PSMA is a
      cell-surface glycoprotein expressed on prostate cancer cells and the neovascular
      endothelium of multiple carcinomas. We show that primary T cells harvested from
      five of five patients with different stages of prostate cancer and transduced
      with the Pz-1 receptor readily lyse prostate cancer cells. Having established a
      culture system using fibroblasts that express PSMA, we next show that T cells
      expressing the Pz-1 receptor release cytokines in response to cell-bound PSMA.
      Furthermore, we show that the cytokine release is greatly augmented by B7.1
      mediated costimulation. Thus, our findings support the feasibility of adoptive
      cell therapy by using genetically engineered T cells in prostate cancer patients
      and suggest that both CD4+ and CD8+ T lymphocyte functions can be synergistically
      targeted against tumor cells.

PMID- 10933047
TI  - Inhibition of T-cell acute lymphoblastic leukemia proliferation in vivo by re
      expression of the p16INK4a tumor suppressor gene.
AB  - T-cell acute lymphoblastic leukemia (T-ALL) is characterized by the presence of
      differentiation-inhibited pro- and pre-T-cell blasts. The p16INK4a tumor
      suppressor gene has been shown to be frequently deleted in human T-ALL cases.
      Deletion of p16INK4a may be associated with poor prognosis and relapse of the
      disease. Radiation-induced murine T-ALL in C57B1/6 mice shares pathogenetic and
      molecular characteristics with the human disease. We used the murine disease as a
      model to study the status of the INK4/ARF gene locus and to examine the effect of
      p16INK4a-re-expression in T-ALL cells on their leukemic potential in vivo. In 9
      of 17 radiation-induced murine T-ALL cell lines, the p16INK4a protein was not
      expressed as determined by immunoblotting. Southern blot analysis revealed
      homozygous deletions of the p16INK4a gene locus in three of the nine lines, along
      with the genes encoding p15INK4b and p19ARF. Transduction of p16INK4a-negative T
      ALL lines with retrovirus encoding p16INK4a significantly inhibited their in
      vitro proliferation by inducing G1-arrest. Importantly, re-expression of p16INK4a
      in p16INK4a-negative T-ALL cells obliterated the induction of lethal disseminated
      leukemia in syngeneic mice. This is the first demonstration that re-establishment
      of p16INK4a expression is critical for in vivo growth regulation of T-ALL cells.

PMID- 10933048
TI  - Induction and characterization of human glioma clones with different
      radiosensitivities.
AB  - To facilitate investigation of the molecular mechanisms of tumor cell
      radiosensitivities, we have generated a set of clones with different
      radiosensitivities from a human glioma cell line U-251 MG-Ho. Forty-four colonies
      were isolated by subjecting parent cells to the mutagen N-methylnitrosourea and
      then irradiating these cells with increasing doses of x-rays. About half of the
      clones displayed different radiosensitivities than the parent cells. We selected
      one of the most sensitive clones (X3i) and one of the most resistant clones (Y6)
      for further study. Isoeffective doses for these two clones differed by about a
      factor of 1.7; the relative radiosensitivities of both clones were stable for at
      least 30 cell culture passages. These two clones do not differ significantly in
      either the induction or repair of radiation-induced DNA double-strand breaks as
      measured by pulsed field gel electrophoresis. Radiation-induced apoptosis
      measured by terminal deoxynucleotide transferase-mediated dUTP nick end labeling
      assay and micronucleus formation were similar in both clones. However,
      potentially lethal damage repair was greater in the radioresistant Y6 clone than
      in the radiosensitive X3i clone as determined by colony-forming efficiency assay.

PMID- 10933050
TI  - Functional coexpression of HSV-1 thymidine kinase and green fluorescent protein:
      implications for noninvasive imaging of transgene expression.
AB  - Current gene therapy technology is limited by the paucity of methodology for
      determining the location and magnitude of therapeutic transgene expression in
      vivo. We describe and validate a paradigm for monitoring therapeutic transgene
      expression by noninvasive imaging of the herpes simplex virus type 1 thymidine
      kinase (HSV-1-tk) marker gene expression. To test proportional coexpression of
      therapeutic and marker genes, a model fusion gene comprising green fluorescent
      protein (gfp) and HSV-1-tk genes was generated (tkgfp gene) and assessed for the
      functional coexpression of the gene product, TKGFP fusion protein, in rat 9L
      gliosarcoma, RG2 glioma, and W256 carcinoma cells. Analysis of the TKGFP protein
      demonstrated that it can serve as a therapeutic gene by rendering tkgfp
      transduced cells sensitive to ganciclovir or as a screening marker useful for
      identifying transduced cells by fluorescence microscopy or fluorescence-activated
      cell sorting (FACS). TK and GFP activities in the TKGFP fusion protein were
      similar to corresponding wild-type proteins and accumulation of the HSV-1-tk
      specific radiolabeled substrate, 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5
      iodo-uracil (FIAU), in stability transduced clones correlated with gfp
      fluorescence intensity over a wide range of expression levels. The tkgfp fusion
      gene itself may be useful in developing novel cancer gene therapy approaches.
      Valuable information about the efficiency of gene transfer and expression could
      be obtained by non-invasive imaging of tkgfp expression with FIAU and clinical
      imaging devices (gamma camera, positron-emission tomography [PET], single photon
      emission computed tomography [SPECT]), and/or direct visualization of gfp
      expression in situ by fluorescence microscopy or endoscopy.

PMID- 10933049
TI  - Cytochromes P450 are expressed in proliferating cells in Barrett's metaplasia.
AB  - The expression of cytochromes P450 (CYP) in Barrett's esophagus and esophageal
      squamous mucosa was investigated. Esophagectomy specimens from 23 patients were
      examined for CYP expression of CYP1A2, CYP3A4, CYP2C9/10, and CYP2E1 by
      immunohistochemical analysis, and the expression of CYP1A1, CYP3A4, CYP1B1,
      CYP2E1, and CYP2C9/10 in these tissues was further confirmed by reverse
      transcription polymerase chain reaction. Immunohistochemical analysis of
      esophageal squamous mucosa (n = 12) showed expression of CYP1A2, CYP3A4, CYP2E1,
      and CYP2C9/10 proteins, but it was noted that cells within the basal
      proliferative zone did not express CYPs. Immunohistochemical analysis of
      Barrett's esophagus (n = 13) showed expression of CYP1A2, CYP3A4, CYP2E1, and
      CYP2C9/10 that was prominent in the basal glandular regions, which are areas
      containing a high percentage of actively proliferating cells. Immunohistochemical
      staining for both proliferating cell nuclear antigen and the CYPs further
      supported the colocalization of CYP expression to areas of active cell
      proliferation in Barrett's esophagus, whereas in the esophageal squamous
      epithelium, CYP expression is limited to cells that are not proliferating. RT-PCR
      with amplification product sequence analysis confirmed CYP1A1, CYP3A4, CYP1B1,
      CYP2E1, and CYP2C9/10 mRNA expression in Barrett's esophagus. These data suggest
      that the potential ability of cells in Barrett's esophagus to both activate
      carcinogens and proliferate may be important risk factors affecting
      carcinogenesis in this metaplastic tissue.

PMID- 10933051
TI  - Replication-competent herpes simplex virus vector G207 and cisplatin combination
      therapy for head and neck squamous cell carcinoma.
AB  - Replication-competent virus vectors are attractive therapeutic agents for cancer.
      G207, a second-generation, multimutated herpes simplex virus type 1 (HSV-1), is
      one such vector that is safe in primates and efficacious against human tumors in
      athymic mice. Squamous cell carcinoma is the most frequently encountered
      malignancy of the head and neck, and the chemotherapeutic agent cisplatin is a
      standard treatment for recurrent head and neck cancer. In this study we examine
      the therapeutic potential of G207, alone and in combination with cisplatin,
      against squamous cell carcinoma. Human squamous cell carcinoma cell lines are
      sensitive to G207 replication and cytotoxicity in vitro at a multiplicity of
      infection of 0.01, including cisplatin sensitive (UMSCC-22A), moderately
      sensitive (UMSCC-38), and weakly sensitive (SQ20B) cell lines. Cisplatin did not
      inhibit the cytopathic effect of G207. G207 inhibited the growth of established
      subcutaneous head and neck tumors in athymic mice. The therapeutic effects of
      cisplatin and G207 in vivo were independent. However, in cisplatin-sensitive
      tumors (UMSCC-38), combination therapy resulted in 100% cures in contrast to 42%
      with G207 or 14% with cisplatin alone. We conclude that G207 should be considered
      for the treatment of head and neck cancer and that combination with
      chemotherapeutic agents may improve efficacy.

PMID- 10933052
TI  - Sulindac sulfide, but not sulindac sulfone, inhibits colorectal cancer growth.
AB  - Sulindac sulfide, a metabolite of the nonsteroidal antiinflammatory drug (NSAID)
      sulindac sulfoxide, is effective at reducing tumor burden in both familial
      adenomatous polyposis patients and in animals with colorectal cancer. Another
      sulindac sulfoxide metabolite, sulindac sulfone, has been reported to have
      antitumor properties without inhibiting cyclooxygenase activity. Here we report
      the effect of sulindac sulfone treatment on the growth of colorectal carcinoma
      cells. We observed that sulindac sulfide or sulfone treatment of HCA-7 cells led
      to inhibition of prostaglandin E2 production. Both sulindac sulfide and sulfone
      inhibited HCA-7 and HCT-116 cell growth in vitro. Sulindac sulfone had no effect
      on the growth of either HCA-7 or HCT-116 xenografts, whereas the sulfide
      derivative inhibited HCA-7 growth in vivo. Both sulindac sulfide and sulfone
      inhibited colon carcinoma cell growth and prostaglandin production in vitro, but
      sulindac sulfone had no effect on the growth of colon cancer cell xenografts in
      nude mice.

PMID- 10933053
TI  - HPV16-E7 expression causes fluorodeoxyuridine-mediated radiosensitization in
      SW620 human colon cancer cells.
AB  - We have reported that HT29 colon cancer cells, which are radiosensitized by
      fluorodeoxyuridine (FdUrd), exhibit a greater increase in cyclin E-dependent
      kinase activity and progress further into S phase in the presence of FdUrd than
      do SW620 colon cancer cells, which are only minimally sensitized by this drug
      (Cancer Res 56: 3203, 1996). Although these findings suggested that the ability
      to progress into S phase in the presence of FdUrd permits cells to be
      radiosensitized, we wished to test this hypothesis by attempting to drive SW620
      human colon cells into S phase by transducing them with the HPV16-E7 gene. Two
      parameter flow cytometry showed that E7-transduced cells progressed through S
      phase after radiation and FdUrd treatment more rapidly than SW620 parental cells.
      We found that E7-transduced SW620 cells were significantly radiosensitized by
      FdUrd (100 nmol/L, 14 hours) with an enhancement ratio for 2 clones of 1.47 +/-
      0.03 and 1.51 +/- 0.14, compared with 1.24 +/- 0.04 in SW620 parental cells.
      These data strongly support the hypothesis that dysregulation of S-phase
      progression is an important factor in FdUrd-mediated radiosensitization.

PMID- 10933056
TI  - BRCA1 partially reverses the transforming activity of the ras oncogene.
AB  - The BRCA1 gene is associated with hereditary breast and ovarian cancers. BRCA1
      fits the model of a classic tumor suppressor gene, a hypothesis supported by
      recent work demonstrating that expression of BRCA1 inhibits growth of breast and
      ovarian cancer cell lines. The present study was designed to test the potential
      of BRCA1 to reverse the transforming activity of the ras oncogene. The v-Ha ras
      oncogene was cloned downstream of the retrovirus LTR and stably expressed in Rat
      1 cells (Rat-1/ras). Rat-1/ras (R/R) cells were fully transformed as indicated by
      change in morphology, colony formation in soft-agarose and tumor induction in
      nude mice. BRCA1 was stably expressed in R/R cells under the CMV promoter (R/R
      BRCA1). The expression of ras and BRCA1 was confirmed by Western blot using
      monoclonal antibodies (mAbs) specific to ras and BRCA1, respectively. R/R-BRCA1
      cells grew slower than the negative control, which was R/R cells transfected with
      vector alone (R/R-pCEP4). R/R-BRCA1 cells generated approximately 5 to 10 times
      less colonies in a soft-agarose assay compared to the negative control. When
      injected into nude mice, R/R-BRCA1 cells exhibited a delayed onset of
      tumorigenesis and generated smaller tumors compared to R/R or R/R-pCEP4 cells.
      These data strongly suggest that BRCA1 partially reverses the transforming
      activity of the v-Ha ras oncogene indicating that BRCA1 can bypass the effects of
      the v-Ha ras oncogene on cell growth. BRCA1, therefore, may be used in therapy of
      tumors arising due to activation of v-Ha ras oncogene.

PMID- 10933057
TI  - Invasiveness of hepatocellular carcinoma cell lines: contribution of membrane
      type 1 matrix metalloproteinase.
AB  - Intrahepatic metastasis is one of the malignant features of hepatocellular
      carcinoma (HCC). Matrix metalloproteinases (MMPs) and urokinase-type plasminogen
      activator (u-PA)/plasmin, are known to be associated with the invasive properties
      of various types of tumor cells. In this study, we examined which proteinases
      play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6
      cells constitutively expressed mRNAs for both membrane-type 1 matrix
      metalloproteinase (MT1-MMP) and u-PA and invaded through reconstituted MATRIGEL
      in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not
      invade. However, hepatocyte growth factor (HGF) induced MT1-MMP expression on the
      surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a
      concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was
      induced in HGF-treated JHH-7 cells. MMP inhibitor, rather than serine proteinase
      inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC
      cell lines into athymic nude mice caused visible intrahepatic metastases in vivo.
      Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured
      JHH-7 cells did not. These findings suggest that MT1-MMP plays an important role
      in the invasive properties of HCC cells, and that HGF modifies the invasive
      properties of noninvasive HCC cells.

PMID- 10933055
TI  - HSV-1-based vectors for gene therapy of neurological diseases and brain tumors:
      part II. Vector systems and applications.
AB  - Many properties of HSV-1 are especially suitable for using this virus as a vector
      to treat diseases affecting the central nervous system (CNS), such as Parkinson's
      disease or malignant gliomas. These advantageous properties include natural
      neurotropism, high transduction efficiency, large transgene capacity, and the
      ability of entering a latent state in neurons. Selective oncolysis in combination
      with modulation of the immune response mediated by replication-conditional HSV-1
      vectors appears to be a highly promising approach in the battle against malignant
      glioma. Helper virus-free HSV/AAV hybrid amplicon vectors have great promise in
      mediating long-term gene expression in the PNS and CNS for the treatment of
      various neurodegenerative disorders or chronic pain. Current research focuses on
      the design of HSV-1-derived vectors which are targeted to certain cell types and
      support transcriptionally regulatable transgene expression. Here, we review the
      recent developments on HSV-1-based vector systems and their applications in
      experimental and clinical gene therapy protocols.

PMID- 10933058
TI  - Killing of brain tumor cells by hypoxia-responsive element mediated expression of
      BAX.
AB  - The presence of radioresistant hypoxic cells in human brain tumors limits the
      overall effectiveness of conventional fractionated radiation therapy. Tumor
      specific therapies that target hypoxic cells are clearly needed. We have
      investigated the expression of suicide genes under hypoxia by a hypoxia
      responsive element (HRE), which can be activated through hypoxia-inducible factor
      1 (HIF-1). We transfected plasmids containing multiple copies of HRE into U-87 MG
      and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ
      gene expression under anoxia. Gene expression under anoxia versus oxia was
      increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI
      cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87
      MG cells was induced by the plasmid that contained three HREs, but not by the
      plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the
      control of HREs, cells transfected with the BAX plasmids were preferentially
      killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated
      gene expression is active in brain tumor cells, and that the amount of increased
      gene expression obtained is dependent on the cell line, the HRE copy number, and
      the degree of hypoxia.

PMID- 10933054
TI  - HSV-1-based vectors for gene therapy of neurological diseases and brain tumors:
      part I. HSV-1 structure, replication and pathogenesis.
AB  - The design of effective gene therapy strategies for brain tumors and other
      neurological disorders relies on the understanding of genetic and
      pathophysiological alterations associated with the disease, on the biological
      characteristics of the target tissue, and on the development of safe vectors and
      expression systems to achieve efficient, targeted and regulated, therapeutic gene
      expression. The herpes simplex virus type 1 (HSV-1) virion is one of the most
      efficient of all current gene transfer vehicles with regard to nuclear gene
      delivery in central nervous system-derived cells including brain tumors. HSV-1
      related research over the past decades has provided excellent insight into the
      structure and function of this virus, which, in turn, facilitated the design of
      innovative vector systems. Here, we review aspects of HSV-1 structure,
      replication and pathogenesis, which are relevant for the engineering of HSV-1
      based vectors.

PMID- 10933060
TI  - Identification and characterization of CD44RC, a novel alternatively spliced
      soluble CD44 isoform that can potentiate the hyaluronan binding activity of cell
      surface CD44.
AB  - Soluble CD44 proteins generated by proteolytic cleavage or aberrant intron
      retention have been shown to antagonize the ligand binding activity of the
      corresponding cell surface receptor, inducing apoptosis and inhibiting tumor
      growth. Interestingly, such findings appear to contradict recent studies
      demonstrating a correlation between the presence of high levels of soluble CD44
      in the serum of cancer patients and poor prognosis. In the present study, we
      report the cloning of a novel, naturally occurring, differentially expressed,
      soluble CD44 isoform, designated CD44RC, which, in contrast to previously
      described soluble CD44 proteins, can dramatically enhance the hyaluronan binding
      activity of cell surface CD44. Sequence analysis suggests that CD44RC is
      generated by an alternative splicing event in which the 3' end of CD44 exon 2 is
      spliced into an internal splice acceptor site present within exon 18, altering
      reading frame and giving rise to a soluble protein with a unique COOH terminus.
      Functional studies suggest that CD44RC enhances hyaluronan binding by adhering to
      chondroitin sulfate side-chains attached to cell surface CD44, generating a
      multivalent complex with increased avidity for hyaluronan.

PMID- 10933059
TI  - Treatment of experimental brain tumors with trombospondin-1 derived peptides: an
      in vivo imaging study.
AB  - Antiangiogenic and antiproliferative effects of synthetic D-reverse peptides
      derived from the type 1 repeats of thrombospondin (TSP1) were studied in rodent
      C6 glioma and 9L gliosarcomas. To directly measure tumor size and vascular
      parameters, we employed in vivo magnetic resonance (MR) imaging and corroborated
      results by traditional morphometric tissue analysis. Rats bearing either C6 or 9L
      tumors were treated with TSP1-derived peptide (D-reverse amKRFKQDGGWSHWSPWSSac,
      n=13) or a control peptide (D-reverse amKRAKQAGGASHASPASSac, n=12) at 10 mg/kg,
      administered either intravenously or through subcutaneous miniosmotic pumps
      starting 10 days after tumor implantation. Eleven days later, the effect of
      peptide treatment was evaluated. TSP1 peptide-treated 9L tumors (50.7+/-44.2 mm3,
      n=7) and C6 tumors (41.3+/-34.2 mm3, n=6) were significantly smaller than tumors
      treated with control peptide (9L: 215.7+/-67.8 mm3, n=6; C6: 184.2+/-105.2 mm3,
      n=6). In contrast, the in vivo vascular volume fraction, the mean vascular area
      (determined by microscopy), and the microvascular density of tumors were not
      significantly different in any of the experimental groups. In cell culture, TSP1,
      and the amKRFKQDGGWSHWSPWSSac peptide showed antiproliferative effects against C6
      with an IC of 45 nM for TSP1. These results indicate that TSP1-derived peptides
      retard brain tumor growth presumably as a result of slower de novo blood vessel
      formation and synergistic direct antiproliferative effects on tumor cells. We
      also show that in vivo MR imaging can be used to assess treatment efficacy of
      novel antiangiogenic drugs non-invasively, which has obvious implications for
      clinical trials.

PMID- 10933061
TI  - Promotion of tumor invasion by cooperation of granulocytes and macrophages
      activated by anti-tumor antibodies.
AB  - We investigated the potential role of anti-tumor antibodies and tumor antigens in
      the formation of immune complexes which promote matrix degradation and
      angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in
      tumor invasion and metastasis. In vitro invasion assays and in vivo models of
      metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes
      which induce granulocytes and macrophages together to mediate tumor invasion and
      metastasis by processes including extracellular matrix degradation and
      angiogenesis. These results suggest the existence of a tumor promoting role of a
      B-cell immune response induced by shed tumor associated antigens of solid,
      nonlymphoid tumors.

PMID- 10933062
TI  - DNA damage measured by the comet assay in head and neck cancer patients treated
      with tirapazamine.
AB  - Tirapazamine (TPZ) [3-amino-1,2,4-benzotriazine 1,4-dioxide, SR4233, WIN 59075,
      and Tirazone] is a novel anticancer drug that is selectively activated by the low
      oxygen environment in solid tumors. By killing the radioresistant hypoxic cells,
      TPZ potentiates the antitumor efficacy of fractionated irradiation of
      transplanted tumors in mice. As this cell kill is closely correlated with TPZ
      induced DNA damage, we investigated whether human head and neck cancers would
      show DNA damage similar to that seen in mouse tumors following TPZ
      administration. TPZ-induced DNA damage in both transplanted tumors in mice and in
      neck nodes of 13 patients with head and neck cancer was assessed using the
      alkaline comet assay on cells obtained from fine-needle aspirates. The oxygen
      levels of the patients' tumors were also measured using a polarographic oxygen
      electrode. Cells from the patients' tumors showed DNA damage immediately
      following TPZ administration that was comparable to, or greater than, that seen
      with transplanted mouse tumors. The heterogeneity of DNA damage in the patients'
      tumors was greater than that of individual mouse tumors and correlated with tumor
      hypoxia. The similarity of TPZ-induced DNA damage in human and rodent tumors
      suggests that tirapazamine should be effective when added to radiotherapy or to
      cisplatin-based chemotherapy in head and neck cancers.

PMID- 10933064
TI  - Imaging in cancer: a National Cancer Institute "extraordinary opportunity".

PMID- 10933063
TI  - Relationship of p53 mutations to epidermal cell proliferation and apoptosis in
      human UV-induced skin carcinogenesis.
AB  - Human skin is continually subjected to UV-irradiation with the p53 gene playing a
      pivotal role in repair of UV-induced DNA damage and apoptosis. Consequently, p53
      alterations are early events in human UV-induced skin carcinogenesis. We studied
      13 squamous cell carcinomas (SCC), 16 actinic keratoses (AK), 13 samples adjacent
      to an AK (chronically sun-damaged), and 14 normal-appearing skin samples for p53
      mutation, p53 immunostaining (IHC), apoptosis (in situ TUNEL and morphology), and
      proliferation (PCNA). The frequency of p53 mutation increased from 14% in normal
      skin, to 38.5% in sun-damaged skin, 63% in AK, and 54% in SCC. p53 IHC increased
      similarly. Apoptosis (TUNEL) increased from 0.06 +/- 0.02%, to 0.1 +/- 0.2, 0.3
      +/- 0.3, and 0.4 +/- 0.3 in normal skin, sun-damaged skin, AK, and SCC,
      respectively. Apoptosis was strongly correlated with proliferation (i.e., TUNEL
      and PCNA, r = 0.7, P < 0.0001), and proliferation was significantly increased in
      the progression from normal skin to SCC. Bax was significantly increased in SCC
      compared to AK. These data imply that apoptosis in samples with a high frequency
      of p53 mutation may not necessarily be p53-dependent. We suggest that there is a
      mechanism for apoptosis in response to increased cellular proliferation that is
      p53-independent.

PMID- 10933065
TI  - Optical coherence tomography: an emerging technology for biomedical imaging and
      optical biopsy.
AB  - Optical coherence tomography (OCT) is an emerging technology for performing high
      resolution cross-sectional imaging. OCT is analogous to ultrasound imaging,
      except that it uses light instead of sound. OCT can provide cross-sectional
      images of tissue structure on the micron scale in situ and in real time. Using
      OCT in combination with catheters and endoscopes enables high-resolution
      intraluminal imaging of organ systems. OCT can function as a type of optical
      biopsy and is a powerful imaging technology for medical diagnostics because
      unlike conventional histopathology which requires removal of a tissue specimen
      and processing for microscopic examination, OCT can provide images of tissue in
      situ and in real time. OCT can be used where standard excisional biopsy is
      hazardous or impossible, to reduce sampling errors associated with excisional
      biopsy, and to guide interventional procedures. In this paper, we review OCT
      technology and describe its potential biomedical and clinical applications.

PMID- 10933066
TI  - Non-invasive in vivo characterization of breast tumors using photon migration
      spectroscopy.
AB  - Frequency-domain photon migration (FDPM) is a non-invasive optical technique that
      utilizes intensity-modulated, near-infrared (NIR) light to quantitatively measure
      optical properties in thick tissues. Optical properties (absorption, mu(a), and
      scattering, mu(s)', parameters) derived from FDPM measurements can be used to
      construct low-resolution (0.5 to 1 cm) functional images of tissue hemoglobin
      (total, oxy-, and deoxy-forms), oxygen saturation, blood volume fraction, water
      content, fat content and cellular structure. Unlike conventional NIR
      transillumination, FDPM enables quantitative analysis of tissue absorption and
      scattering parameters in a single non-invasive measurement. The unique functional
      information provided by FDPM makes it well-suited to characterizing tumors in
      thick tissues. In order to test the sensitivity of FDPM for cancer diagnosis, we
      have initiated clinical studies to quantitatively determine normal and malignant
      breast tissue optical and physiological properties in human subjects.
      Measurements are performed using a non-invasive, multi-wavelength, diode-laser
      FDPM device optimized for clinical studies. Results show that ductal carcinomas
      (invasive and in situ) and benign fibroadenomas exhibit 1.25 to 3-fold higher
      absorption than normal breast tissue. Within this group, absorption is greatest
      for measurements obtained from sites of invasive cancer. Optical scattering is
      approximately 20% greater in pre-menopausal versus post-menopausal subjects due
      to differences in gland/cell proliferation and collagen/fat content. Spatial
      variations in tissue scattering reveal the loss of differentiation associated
      with breast disease progression. Overall, the metabolic demands of hormonal
      stimulation and tumor growth are detectable using photon migration techniques.
      Measurements provide quantitative optical property values that reflect changes in
      tissue perfusion, oxygen consumption, and cell/matrix development.

PMID- 10933067
TI  - Use of reporter genes for optical measurements of neoplastic disease in vivo.
AB  - Revealing the cellular and molecular changes associated with cancer, as they
      occur in intact living animal models of human neoplastic disease, holds
      tremendous potential for understanding disease mechanisms and elucidating
      effective therapies. Since light is transmitted through mammalian tissues, at a
      low level, optical signatures conferred on tumor cells by expression of reporter
      genes encoding bioluminescent and fluorescent proteins can be detected externally
      using sensitive photon detection systems. Expression of reporter genes, such as
      the bioluminescent enzyme firefly luciferase (Luc) or variants of green
      fluorescent protein (GFP) in transformed cells, can effectively be used to reveal
      molecular and cellular features of neoplasia in vivo. Tumor cell growth and
      regression in response to various therapies have been evaluated non-invasively in
      living experimental animals using these reporter genes. Detection of Luc-labeled
      cells in vivo was extremely sensitive with signals over background from as few as
      1000 human tumor cells distributed throughout the peritoneal cavity of a mouse
      with linear relationships between cell number and signal intensity over five
      logs. GFP offers the strength of high-resolution ex vivo analyses following in
      vivo localization of the tumor. The dynamic range of Luc detection allows the
      full disease course to be monitored since disease progression from small numbers
      of cells to extensive disease can be assessed. As such, therapies that target
      minimal disease as well as those designed for late stage disease can be readily
      evaluated in animal models. Real time spatiotemporal analyses of tumor cell
      growth can reveal the dynamics of neoplastic disease, and facilitate rapid
      optimization of effective treatment regimens. Thus, these methods improve the
      predictability of animal models of human disease as study groups can be followed
      over time, and can accelerate the development of therapeutic strategies.

PMID- 10933069
TI  - High resolution X-ray computed tomography: an emerging tool for small animal
      cancer research.
AB  - Dedicated high-resolution small animal imaging systems have recently emerged as
      important new tools for cancer research. These new imaging systems permit
      researchers to noninvasively screen animals for mutations or pathologies and to
      monitor disease progression and response to therapy. One imaging modality, X-ray
      microcomputed tomography (microCT) shows promise as a cost-effective means for
      detecting and characterizing soft-tissue structures, skeletal abnormalities, and
      tumors in live animals. MicroCT systems provide high-resolution images (typically
      50 microns or less), rapid data acquisition (typically 5 to 30 minutes),
      excellent sensitivity to skeletal tissue and good sensitivity to soft tissue,
      particularly when contrast-enhancing media are employed. The development of
      microCT technology for small animal imaging is reviewed, and key considerations
      for designing small animal microCT imaging protocols are summarized. Recent
      studies on mouse prostate, lung and bone tumor models are overviewed.

PMID- 10933068
TI  - Intravital fluorescence videomicroscopy to study tumor angiogenesis and
      microcirculation.
AB  - Angiogenesis and microcirculation play a central role in growth and metastasis of
      human neoplasms, and, thus, represent a major target for novel treatment
      strategies. Mechanistic analysis of processes involved in tumor vascularization,
      however, requires sophisticated in vivo experimental models and techniques.
      Intravital microscopy allows direct assessment of tumor angiogenesis,
      microcirculation and overall perfusion. Its application to the study of tumor
      induced neovascularization further provides information on molecular transport
      and delivery, intra- and extravascular cell-to-cell and cell-to-matrix
      interaction, as well as tumor oxygenation and metabolism. With the recent
      advances in the field of bioluminescence and fluorescent reporter genes,
      appropriate for in vivo imaging, the intravital fluorescent microscopic approach
      has to be considered a powerful tool to study microvascular, cellular and
      molecular mechanisms of tumor growth.

PMID- 10933070
TI  - Characterizing tumors using metabolic imaging: PET imaging of cellular
      proliferation and steroid receptors.
AB  - Treatment decisions in oncology are increasingly guided by information on the
      biologic characteristics of tumors. Currently, patient-specific information on
      tumor biology is obtained from the analysis of biopsy material. Positron emission
      tomography (PET) provides quantitative estimates of regional biochemistry and
      receptor status and can overcome the sampling error and difficulty in performing
      serial studies inherent with biopsy. Imaging using the glucose metabolism tracer,
      2 -deoxy-2- fluoro-D-glucose (FDG), has demonstrated PET's ability to guide
      therapy in clinical oncology. In this review, we highlight PET approaches to
      imaging two other aspects of tumor biology: cellular proliferation and tumor
      steroid receptors. We review the biochemical and biologic processes underlying
      the imaging, positron-emitting radiopharmaceuticals that have been developed,
      quantitative image-analysis considerations, and clinical studies to date. This
      provides a basis for evaluating future developments in these promising
      applications of PET metabolic imaging.

PMID- 10933071
TI  - Fluorescence spectroscopy of neoplastic and non-neoplastic tissues.
AB  - Fast and non-invasive, diagnostic techniques based on fluorescence spectroscopy
      have the potential to link the biochemical and morphologic properties of tissues
      to individual patient care. One of the most widely explored applications of
      fluorescence spectroscopy is the detection of endoscopically invisible, early
      neoplastic growth in epithelial tissue sites. Currently, there are no effective
      diagnostic techniques for these early tissue transformations. If fluorescence
      spectroscopy can be applied successfully as a diagnostic technique in this
      clinical context, it may increase the potential for curative treatment, and thus,
      reduce complications and health care costs. Steady-state, fluorescence
      measurements from small tissue regions as well as relatively large tissue fields
      have been performed. To a much lesser extent, time-resolved, fluorescence
      measurements have also been explored for tissue characterization. Furthermore,
      sources of both intrinsic (endogenous fluorophores) and extrinsic fluorescence
      (exogenous fluorophores) have been considered. The goal of the current report is
      to provide a comprehensive review on steady-state and time-resolved, fluorescence
      measurements of neoplastic and non-neoplastic, biologic systems of varying
      degrees of complexity. First, the principles and methodology of fluorescence
      spectroscopy are discussed. Next, the endogenous fluorescence properties of
      cells, frozen tissue sections and excised and intact bulk tissues are presented;
      fluorescence measurements from both animal and human tissue models are discussed.
      This is concluded with future perspectives.

PMID- 10933072
TI  - Imaging transgene expression with radionuclide imaging technologies.
AB  - A variety of imaging technologies are being investigated as tools for studying
      gene expression in living subjects. Noninvasive, repetitive and quantitative
      imaging of gene expression will help both to facilitate human gene therapy trials
      and to allow for the study of animal models of molecular and cellular therapy.
      Radionuclide approaches using single photon emission computed tomography (SPECT)
      and positron emission tomography (PET) are the most mature of the current imaging
      technologies and offer many advantages for imaging gene expression compared to
      optical and magnetic resonance imaging (MRI)-based approaches. These advantages
      include relatively high sensitivity, full quantitative capability (for PET), and
      the ability to extend small animal assays directly into clinical human
      applications. We describe a PET scanner (microPET) designed specifically for
      studies of small animals. We review "marker/reporter gene" imaging approaches
      using the herpes simplex type 1 virus thymidine kinase (HSV1-tk) and the dopamine
      type 2 receptor (D2R) genes. We describe and contrast several radiolabeled probes
      that can be used with the HSV1-tk reporter gene both for SPECT and for PET
      imaging. We also describe the advantages/disadvantages of each of the assays
      developed and discuss future animal and human applications.

PMID- 10933073
TI  - Applications of magnetic resonance in model systems: tumor biology and
      physiology.
AB  - A solid tumor presents a unique challenge as a system in which the dynamics of
      the relationship between vascularization, the physiological environment and
      metabolism are continually changing with growth and following treatment. Magnetic
      resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) studies have
      demonstrated quantifiable linkages between the physiological environment,
      angiogenesis, vascularization and metabolism of tumors. The dynamics between
      these parameters continually change with tumor aggressiveness, tumor growth and
      during therapy and each of these can be monitored longitudinally, quantitatively
      and non-invasively with MRI and MRS. An important aspect of MRI and MRS studies
      is that techniques and findings are easily translated between systems. Hence, pre
      clinical studies using cultured cells or experimental animals have a high
      connectivity to potential clinical utility. In the following review, leaders in
      the field of MR studies of basic tumor physiology using pre-clinical models have
      contributed individual sections according to their expertise and outlook. The
      following review is a cogent and timely overview of the current capabilities and
      state-of-the-art of MRI and MRS as applied to experimental cancers. A companion
      review deals with the application of MR methods to anticancer therapy.

PMID- 10933076
TI  - Noninvasive monitoring of airway inflammation.

PMID- 10933077
TI  - Thunderstorm-associated asthma in an inland town in south-eastern Australia. Who
      is at risk?
AB  - The aim of the study was to characterize patients at risk of asthma exacerbation
      during spring thunderstorms and identify potential measures to ameliorate the
      impact of those events. A case-control study was conducted among patients aged 7
      60 yrs, who attended Wagga Hospital (NSW, Australia) for asthma during the period
      of 1 June 1997 to 31 October 1997. One hundred and eighty-three patients who
      attended on 30 and 31 October 1997 were the cases and the remaining 121 patients
      were the controls. Questionnaire data were obtained from 148 (81%) cases and 91
      (75%) controls. One hundred and thirty-eight (95%) cases who attended during the
      thunderstorm gave a history of hayfever prior to the event compared to 66 (74%)
      controls who attended at other times (odds ratio (OR) 6.01, 95% confidence
      interval (CI) 2.55-14.15); 111 (96%) cases were allergic to rye grass pollen
      compared to 47 (64%) controls (OR 23.6, 95% CI 6.6-84.3). Among subjects with a
      prior diagnosis of asthma (64% cases and 82% controls), controls (56%) were more
      likely to be taking inhaled steroids at time of the thunderstorm than cases (27%,
      OR 0.3, 95% CI 0.16-0.57). History of hayfever and allergy to rye grass are
      strong predictors for asthma exacerbation during thunderstorms in spring. The
      lower rate of inhaled steroid use in thunderstorm cases suggests that this
      treatment may be effective in preventing severe attacks during thunderstorms.

PMID- 10933074
TI  - Applications of magnetic resonance in model systems: cancer therapeutics.
AB  - The lack of information regarding the metabolism and pathophysiology of
      individual tumors limits, in part, both the development of new anti-cancer
      therapies and the optimal implementation of currently available treatments.
      Magnetic resonance [MR, including magnetic resonance imaging (MRI), magnetic
      resonance spectroscopy (MRS), and electron paramagnetic resonance (EPR)] provides
      a powerful tool to assess many aspects of tumor metabolism and pathophysiology.
      Moreover, since this information can be obtained nondestructively, pre-clinical
      results from cellular or animal models are often easily translated into the
      clinic. This review presents selected examples of how MR has been used to
      identify metabolic changes associated with apoptosis, detect therapeutic response
      prior to a change in tumor volume, optimize the combination of metabolic
      inhibitors with chemotherapy and/or radiation, characterize and exploit the
      influence of tumor pH on the effectiveness of chemotherapy, characterize tumor
      reoxygenation and the effects of modifiers of tumor oxygenation in individual
      tumors, image transgene expression and assess the efficacy of gene therapy. These
      examples provide an overview of several of the areas in which cellular and animal
      model studies using MR have contributed to our understanding of the effects of
      treatment on tumor metabolism and pathophysiology and the importance of tumor
      metabolism and pathophysiology as determinants of therapeutic response.

PMID- 10933078
TI  - Frequency and determinants of exaggerated bronchoconstriction during shortened
      methacholine challenge tests in epidemiological and clinical set-ups.
AB  - The European Respiratory Society guidelines on bronchial provocation testing have
      proposed time-saving procedures, which may lead to unwanted exaggerated
      responses. The frequency and determinants of exaggerated bronchoconstriction in
      response to methacholine inhalation testing in clinical and epidemiological
      settings have not been assessed. The authors evaluated: 1) the prevalence of
      exaggerated bronchoconstriction, 2) its relation to time-saving measures
      (starting methacholine concentration and skipping concentrations); and 3)
      associations between such reactions and risk factors, respiratory symptoms and/or
      lung function parameters. Clinical (n=408) and epidemiological (n=711) groups
      were included. Exaggerated bronchoconstriction was defined as either a fall > or
      =20% following saline or a > or =30% fall in forced expiratory volume in one
      second (FEV1) after methacholine inhalations. Cases were compared with two groups
      of subjects: 1) with measurable bronchial responsiveness (MBR); and 2) without
      MBR. In the epidemiological group, 84 subjects (12%) presented exaggerated
      bronchoconstriction. Skipped concentrations accounted for an exaggerated
      bronchoconstriction in 18 of these. In the clinical group, 41 subjects (10%)
      experienced exaggerated reactions. Skipped concentrations accounted for an
      exaggerated bronchoconstriction in five of these. The provocative concentration
      of methacholine causing a 20% fall in FEV1 values were marginally lower in
      subjects with exaggerated bronchoconstriction. Questionnaire analysis in
      epidemiological subjects showed some symptoms of asthma and rhinitis to be more
      prevalent in cases than in subjects without MBR. In conclusion, methacholine
      inhalation tests with time-saving measures result in a 10% risk of exaggerated
      bronchoconstriction as defined in this study and bronchial responsiveness is more
      prominent in subjects with exaggerated bronchoconstriction.

PMID- 10933075
TI  - Three-dimensional magnetic resonance spectroscopic imaging of brain and prostate
      cancer.
AB  - Clinical applications of magnetic resonance spectroscopic imaging (MRSI) for the
      study of brain and prostate cancer have expanded significantly over the past 10
      years. Proton MRSI studies of the brain and prostate have demonstrated the
      feasibility of noninvasively assessing human cancers based on metabolite levels
      before and after therapy in a clinically reasonable amount of time. MRSI provides
      a unique biochemical "window" to study cellular metabolism noninvasively. MRSI
      studies have demonstrated dramatic spectral differences between normal brain
      tissue (low choline and high N-acetyl aspartate, NAA) and prostate (low choline
      and high citrate) compared to brain (low NAA, high choline) and prostate (low
      citrate, high choline) tumors. The presence of edema and necrosis in both the
      prostate and brain was reflected by a reduction of the intensity of all
      resonances due to reduced cell density. MRSI was able to discriminate necrosis
      (absence of all metabolites, except lipids and lactate) from viable normal tissue
      and cancer following therapy. The results of current MRSI studies also provide
      evidence that the magnitude of metabolic changes in regions of cancer before
      therapy as well as the magnitude and time course of metabolic changes after
      therapy can improve our understanding of cancer aggressiveness and mechanisms of
      therapeutic response. Clinically, combined MRI/MRSI has already demonstrated the
      potential for improved diagnosis, staging and treatment planning of brain and
      prostate cancer. Additionally, studies are under way to determine the accuracy of
      anatomic and metabolic parameters in providing an objective quantitative basis
      for assessing disease progression and response to therapy.

PMID- 10933079
TI  - Long-term effects of asthma education for physicians on patient satisfaction and
      use of health services.
AB  - This randomized clinical trial evaluated the long-term impact of an interactive
      seminar for physicians based on principles of self-regulation on clinician
      behaviour, children's use of health services for asthma, and parent's views of
      physician performance. Seventy-four general practice paediatricians, and 637 of
      their asthma patients aged 1-12 yrs, were randomized to treatment or control.
      Children and parents were blind to physicians' participation. Data were collected
      at baseline and follow-up through self-administered surveys (paediatricians),
      telephone interviews (parents) and medical records. The seminar focused on
      development of communication and teaching skills and use of therapeutic medical
      regimens for asthma as outlined in the National Asthma Education and Prevention
      Program guidelines. Approximately 2 yrs postintervention, treatment group
      physicians were more likely than control physicians to: use protocols for
      delivering asthma education (odds ratio (OR) 4.9, p=0.2), write down for patients
      how to adjust medicines when symptoms change (OR 5.7, p=0.05), and provide more
      guidelines for modifying therapy (OR 3.8, p=0.06). Parents scored treatment group
      physicians higher than control physicians on five specific positive communication
      behaviours. Children seen by treatment group physicians had fewer
      hospitalizations (p=0.03) and those with higher levels of emergency department
      (ED) use at baseline had fewer subsequent ED visits (p=0.03). No differences
      regarding the number of office visits were noted. There were no significant
      differences found between treatment and control group physicians in the amount of
      time spent with patients during office visits (26 versus 29 min) or in the number
      of patients treated with anti-inflammatory medicine. It is concluded that
      interactive asthma seminars for paediatricians had significant long-term benefits
      for their asthma care.

PMID- 10933080
TI  - Interferon-gamma increases IL-12 mRNA expression and attentuates allergic late
      onset airway responses in the Brown Norway rat.
AB  - Interferon gamma is a T-helper cell (Th)-1-type cytokine that has been suggested
      to inhibit the development of an atopic Th2-type profile of cytokine expression.
      The aim of this study was to investigated the effect of exogenous rat interferon
      gamma on antigen-induced airway responses, and on Th1 and Th2-type cytokine
      messenger ribonucleic acid (mRNA) expression in the Brown Norway rat. Rats were
      actively sensitized to ovalbumin and 14 days later underwent an aerosolized
      ovalbumin challenge. Animals were intratracheally administered either interferon
      gamma (3,000 U) or control solvent 30 min prior to, and 2 and 4 h following,
      antigen challenge. Lung resistance was monitored over an 8-h time period. Using
      in situ hybridization and immunocytochemistry, the levels of Th1- (interleukin
      12) and Th2-type (interleukin4 and -5) cytokine mRNA, and major basic protein
      expression in the bronchoalveolar lavage fluid of these rats 8 h after ovalbumin
      challenge were also determined. Administration of interferon gamma attenuated the
      development of the late-onset airways response in ovalbumin-sensitized antigen
      challenged rats (p<0,05). The expression of interleukin-4 and -5 mRNA in the
      bronchoalveolar lavage fluid of interferon gamma treated rats was significantly
      attenuated compared to ovalbumin-challenged saline-treated controls (p<0.001).
      This was accompanied by a significant increase in the expression of interleukin
      12 mRNA, and a reduction in eosinophil numbers. Intratracheal administration of
      interferon gamma modulates the allergic late-onset airways response in rats, and
      this is associated with a reduction in the expression of T-helper cell 2-type
      cytokines and an increase in interleukin-12 messenger ribonucleic acid expression
      within the airways. The present results support a role for interferon gamma in
      the pathophysiology of acute allergic airway responses, possibly by virtue of its
      ability to modulate T-helper cell 1- 2-type cytokine expression within the lungs.

PMID- 10933081
TI  - Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis.
AB  - Exercise-induced asthma (or bronchoconstriction) afflicts millions of people
      worldwide. While generally self-limiting, it can hinder performance and reduce
      activity levels, thus it is an important condition to diagnose and treat. The
      objective of this review was to assess the prophylactic effect of a single dose
      of nedocromil sodium on exercise-induced asthma. The Cochrane Airways Group
      trials register, the Cochrane Controlled Trials Register, Current Contents,
      reference lists of relevant articles, review articles and textbooks were searched
      for randomized trials comparing a single dose of nedocromil to placebo to prevent
      exercise-induced asthma in people >6 yrs of age. Authors and the drug
      manufacturer were contacted for additional trials. Trial quality assessments and
      data extraction were conducted independently by two reviewers. Authors were
      contacted when possible. Twenty trials were included. All were rated as having
      good methodological quality. Nedocromil inhibited bronchoconstriction in all age
      groups. The pooled weighted mean difference for the maximum percentage fall in
      forced expiratory volume in one second was 15.6%, (95% confidence interval (95%
      CI): 13.2-18.1) and for the peak expiratory flow was 15.0% (95% CI: 8.3-21.6).
      These differences are both statistically and clinically significant. After
      nedocromil the time to recover normal lung function was <10 min compared to >30
      min with placebo. Nedocromil had a greater effect on people with a fall in lung
      function of >30% from baseline. There were no significant adverse effects
      reported with this short-term use. In conclusion, Nedocromil taken before
      exercise appears to reduce the severity and duration of exercise-induced
      bronchoconstriction. This effect appears to be more pronounced as severity
      increases.

PMID- 10933082
TI  - The effect of insecticide aerosols on lung function, airway responsiveness and
      symptoms in asthmatic subjects.
AB  - The object of this study was to compare the effect of standard and "low irritant"
      insecticide aerosols on lung function, airway hyperresponsiveness (AHR) and
      symptoms in asthmatic subjects. A double blind randomized, crossover study was
      conducted in 25 asthmatic subjects who reported sensitivity to insecticide
      aerosols. All subjects were exposed for 30 min, on separate occasions, to two
      standard insecticide formulations (A and B), one low irritant formulation (C) and
      a negative control aerosol. Spirometric function and chest, nose and eye symptoms
      were recorded during, and for 90 min after, the exposure. AHR to methacholine was
      measured 90 min after the exposure. Compared to the negative control, the maximum
      fall in forced expiratory volume in one second (FEV1) was slightly greater after
      standard insecticides (mean differences from control +/-95% confidence interval:
      aerosol A, 3.3+/-3.6%, p=0.08; aerosol B, 5.1+/-4.7%, p=0.04), AHR was
      significantly more severe (mean difference from control: aerosol A, 0.35+/-0.29
      doubling doses, p=0.028; aerosol B, 0.52+/-0.43 doubling doses, p=0.028), and
      symptoms were more severe. The low irritant test aerosol (C) did not differ
      significantly from the negative control with respect to FEV1, AHR or symptoms. It
      is concluded that some insecticide aerosols trigger symptoms and falls in lung
      function in some people with asthma. Furthermore, these aerosols may also
      increase airway hyperresponsiveness, although the mechanism of this effect has
      not been determined. The low irritant formulation did not appear to have the same
      effects.

PMID- 10933083
TI  - Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant
      asthmatics.
AB  - Asthma is characterized by chronic airway inflammation resulting from
      overproduction of pro-inflammatory mediators, such as leukotrienes (LT). The
      authors questioned the biosynthetic capacity of asthmatic patients for lipoxins
      (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory
      responses that inhibit pro-inflammatory events. Levels of LXA4, 15-epi-LXA4 and
      LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics
      (AIA), 11 aspirin-tolerant asthmatics (ATA) and eight healthy volunteers using a
      stimulated whole blood protocol. Both LXA4 and 15-epi-LXA4 were generated in
      whole blood activated by the divalent cation ionophore, A23187. Higher levels of
      LXA4 were produced in ATA than either AIA or healthy volunteers. Exposure of AIA
      whole blood to interleukin-3 prior to A23187 did not elevate their reduced
      capacity to generate LXA4. Generation of a bronchoconstrictor, LTC4, was similar
      in both AIA and ATA. Consequently, the ratio of LXA4:LTC4 quantitatively favoured
      the bronchoconstrictor for AIA and differed from both ATA and healthy subjects.
      In addition, the capacity for 15-epi-LXA4 generation was also diminished in AIA,
      since whole blood stimulated in the presence of aspirin gave increased levels
      only in samples from ATA. The present results indicate that asthmatics possess
      the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin
      intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant
      asthmatics for these potentially protective lipid mediators. This previously
      unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant
      asthmatic patients may contribute to their more severe clinical phenotype, and
      represents a novel paradigm for the development of chronic inflammatory
      disorders.

PMID- 10933084
TI  - S and Z alpha1-antitrypsin alleles are risk factors for bronchial
      hyperresponsiveness in young farmers: an example of gene/environment interaction.
AB  - Several studies have found an association between the rare Pi-alleles and asthma
      or bronchial hyperresponsiveness (BHR). This study deals with the effect of Pi
      type on BHR among 2,308 young Danish people living in rural areas with a mean +/-
      SD age of 19.7+/-2.4 yrs. Interviews, pulmonary function testing, bronchial
      histamine provocation and skin-prick tests were performed. Serum alpha1
      antitrypsin levels were determined and phenotyping was performed by means of
      isoelectric focusing and the subjects categorized into four groups: 1) MM and MX;
      2) MS; 3) MZ; and 4) rare, i.e. SZ, SS and ZZ. Among the farmers, a significant
      positive trend for sensitization towards house dust mites was found, ranging from
      12% in the MM group to 22% in the rare Pi-group. A positive test for trend was
      found within the Pi-groups in a one-sided test for doctor-diagnosed asthma with a
      peak prevalence of 40% for these symptoms among smokers in the rare Pi-group. On
      multiple logistic regression analysis, an increased odds ratio (OR) for BHR was
      found among farming school attendants with the rare Pi-alleles. The OR (95%
      confidence interval) was 1.71 (0.84-3.49) for MS, 1.93 (1.10-3.39) for MZ and
      4.34 (1.19-15.8) for the rare Pi-group. Such a relationship was not found among
      the conscripts. These results show that a gene/environment interaction may exist
      between the farming occupation and the rare Pi-alleles, leading to a higher
      proportion of bronchial hyperresponsiveness related to the rare Pi-alleles in
      farming school attendants, in contrast to what is found among other young people
      living in rural areas.

PMID- 10933085
TI  - High-resolution computed tomographic characteristics in acute farmer's lung and
      in its follow-up.
AB  - High resolution computed tomography (HRCT) scans are increasingly used in
      hypersensitivity pneumonitis (HP). This study looked at HRCT findings at
      different phases of farmer's lung (FL), a common form of HP. A cross sectional
      analysis of 95 HRCT scans of FL cases (20 acute, 75 with a history of FL, 48
      still in contact (Ex +) (dairy farm), and 27 who had ceased contact (Ex-)) was
      made. All scans were read independently by two, and if needed by three,
      radiologists blinded to the category. The lungs were divided into six regions
      (fives lobes + lingula), and read for attenuation/mosaic, ground-glass,
      micronodules, fibrosis, and emphysema. A score of 0-3 was given for each region
      and each variable: 0 = absence, 1 =<25% of the surface, 2 = 25-50%, 3 =>50%.
      Mediastinal lymphadenopathy was also noted. Ground glass, predominating in the
      lower lobes, was the most frequent feature in the acute and Ex+ cases. Other
      abnormalities had no preferential distribution. Ex+ had more ground-glass than
      the Ex- (p=0.0025). Emphysema was more frequently seen than interstitial fibrosis
      (p=0.004). Mediastinal lymphadenopathy was present in 26 cases (9 acute, 10 Ex+
      and 7 Ex-). In conclusion, in farmer's lung: 1) ground-glass predominates in the
      lower lobes while the other abnormalities have no anatomic predilection; 2)
      contact avoidance allows a better resolution of computed tomography abnormalities
      than continued exposure; 3) emphysema is a more frequent finding than
      interstitial fibrosis; and 4) the presence of mediastinal lymphadenopathy has no
      negative diagnostic value.

PMID- 10933086
TI  - Environmental exposure to air pollution and allergens and peak flow changes.
AB  - Laboratory-based studies have shown that ozone and nitrogen dioxide can
      potentiate the effect of allergen in sensitized asthmatic subjects, but it is not
      known whether this interaction is important under natural exposure conditions.
      Thirty-five subjects with clinical diagnoses of asthma or chronic obstructive
      pulmonary disease and with a provocative dose causing a 20% fall in forced
      expiratory volume in one second methacholine <12.25 micromol (using the Yan
      method) kept peak expiratory flow (PEF) records for a 4-week period during late
      summer, with concurrent measurement of spore and pollen counts and pollution
      levels. Multiple regression analysis was then used to determine the effect on PEF
      of aeroallergen, and of the interaction between aeroallergen and pollutant
      levels. A statistically significant interaction was demonstrated between total
      spore count and ozone, but not nitrogen dioxide. Mean PEF fell in association
      with increasing spore count (same-day and 24-h lag level) and PEF variability
      increased with increasing spore count (24-h lag level only); both changes were
      greater the higher the prior ozone level. These results suggest that ozone can
      potentiate the effect of aeroallergens in subjects with bronchial hyperreactivity
      under natural exposure conditions. However, the effect was small, and the
      clinical significance of the interaction requires further study.

PMID- 10933087
TI  - The effect of lung biopsy on lung function in diffuse lung disease.
AB  - The aim of this study was to investigate the effect on lung function of lung
      biopsy used in the diagnosis of diffuse lung disease carried out by an open
      procedure or by video-assisted thoracoscopy. One hundred and sixteen patients
      with diffuse lung disease who attended the Royal Brompton Hospital were studied
      retrospectively. Thirty five patients underwent open lung biopsy, and 33 video
      assisted thoracoscopic biopsy and 48 had their diagnosis made without biopsy. All
      patients underwent lung function tests before and after surgery, or at an
      interval of 3-6 months in those who did not undergo biopsy. No significant
      differences were found in changes in lung function between those who had and had
      not undergone biopsy, and the proportions of patients whose lung function
      improved or deteriorated were similar. Lung biopsy by an open procedure or by
      video-assisted thoracoscopy did not differ in its effects on lung function. The
      results for older patients, those with severe disease and those with fibrosing
      alveolitis were the same as for the whole group. Open lung biopsy for the
      diagnosis of diffuse lung disease does not deleteriously affect lung function
      whether carried out by an open or a minimally invasive procedure.

PMID- 10933088
TI  - HLA-Gm/kappam interaction in sarcoidosis. Suggestions for a complex genetic
      structure.
AB  - The aetiology of sarcoidosis is still unknown. Environmental exposures are
      believed to interact with genetic factors in determining the pattern of
      sarcoidosis presentation, progression and prognosis. The frequency of serological
      polymorphism of immunoglobulin G heavy chain (Gm) and kappa light chain (kappam)
      markers in 107 patients with biopsy-proven sarcoidosis and in 227 controls, and
      their interactions with histocompatibility leukocyte antigen (HLA) class I, II,
      and III markers, were studied. A "protective" effect of the Gm(3 5*) phenotype in
      the sarcoid group versus controls (p-value for number of specificities tested
      (p(c))=0.05, odds ratio 0.15) and a reduced frequency of Gm(3 23 5*) in patients
      with advanced chest radiographic stage (Chi-squared (two degrees of
      freedom)(chi2(2df) 17.61, p(c)=0.0058) were observed. With reference to epistatic
      interactions, the combination Gm(3 23 5*)/BfS had a "protective" effect towards
      stage II (chi2(2dt) 13.86, p(c)=0.043). Finally, correspondence analysis defined
      two clusters: HLA-DR4, C4BQ0, Gm(1, 3, 17 23 5*, 21, 28) and BfF associated with
      stage II, and HLA-DR3, C4AQ0, kappam(1) and Gm(3 23 5*) associated with stage I.
      These data further support the hypothesis that sarcoidosis results from an
      interplay of environmental factors and genes, each contributing to the
      susceptibility/resistance to and/or the clinical heterogeneity of the disease. In
      addition, these data provide the first evidence of an interaction between
      immunoglobulin G heavy chain/kappa light chain markers and histocompatibility
      leukocyte antigen class III genes in a disease.

PMID- 10933089
TI  - Prevalence of wheeze during childhood: retrospective and prospective assessment.
AB  - The question "Has your child ever had wheezing or whistling in the chest at any
      time in the past?" is a simple and widely used proxy measure for the lifetime
      prevalence of asthma. Our aim was to test its validity in a longitudinal survey,
      comparing retrospective recall with prospective assessment of lifetime
      prevalence. A population-based cohort of 1,422 children, surveyed twice
      previously, was studied again at age 8-13 yrs by postal questionnaire using
      standardized questions from the International Study of Asthma and Allergies in
      Childhood (ISAAC). Of those traced (1,190) questionnaires were returned by 89%.
      The prevalence of current wheeze was higher than in the previous surveys (20.5%
      versus 12.4% and 12.5%). Reported "wheeze ever" increased significantly from
      survey 1 (15.6%) to survey 2 (22.4%) and survey 3 (39.2%) and was very similar to
      the cumulative lifetime prevalence assessed prospectively over three surveys
      (42.8%). The retrospective question had a good negative predictive value (97%)
      and a reasonable positive predictive value (65%) compared to prospective
      assessment. Children reporting "wheeze ever" (but not current wheeze) in surveys
      1 and 2 had at survey 3 an asthma prevalence higher than never-wheezers but lower
      than current-wheezers. It is concluded that retrospective recall of wheeze at age
      8-13 yrs is a valid proxy measure for the lifetime prevalence of wheeze.

PMID- 10933090
TI  - Similar prevalence of respiratory symptoms and atopy in Estonian schoolchildren
      with changing lifestyle over 4 yrs.
AB  - The prevalence of allergic sensitization and clinical manifestations is low in
      Eastern Europe, despite a continuous increase in industrialized countries with a
      market economy. The aim of the present study was to study changes in the
      prevalence of respiratory symptoms and atopic sensitization over time among
      schoolchildren in Estonia, in relation to environmental changes as the country
      transformed into a market economy. A cross-sectional study of 10-yr-old children
      was carried out between October 1996 and April 1997, employing a questionnaire
      regarding the prevalence of wheezing, rhinitis and itching rash (n=979) and skin
      prick tests with seven inhalant allergens (n=640). The results were compared with
      those of a similar study performed in 1992-1993. The 12-month prevalence of
      wheeze was 8.3%, as compared to 9.4% in 1992-1993 (NS) and of asthma was 2.5
      versus 3.2% (NS). The prevalence of a positive skin-prick test result was 14.3%
      in both studies. Furthermore, the prevalence of sensitivity to the individual
      allergens was similar, except for a significantly higher prevalence of dog
      sensitivity in 1996-1997 (4.7 versus 2.0%). The prevalence of respiratory and
      other potentially allergic symptoms, as well as the prevalence of atopic
      sensitization, remains low in Estonian 10-yr-old children, despite a changing
      lifestyle over the past 4 yrs. This could indicate that the time period was too
      short for environmental changes to affect the prevalence of allergy, or
      alternatively that risk factors associated with a "western lifestyle" are of
      particular significance earlier in life.

PMID- 10933091
TI  - Sputum induction in young cystic fibrosis patients.
AB  - A culture from the lower airway secretions is the optimal sample to guide
      antibiotic therapy in cystic fibrosis (CF) lung disease. The authors therefore
      examined whether sputum induction is an efficient, safe and acceptable procedure
      in CF children without spontaneous expectorations. Nineteen patients were
      studied. Their mean age (range) was 8.6 yrs (4.3-15.2 yrs). Their mean forced
      expiratory volume in one second (FEV1) was 88% predicted (46-122%). NaCl
      solutions from 0.9-6% were inhaled, after baseline lung function tests before and
      after salbutamol. All patients did produce secretions. Alveolar macrophages were
      present in 16/19 induced samples. The procedure induced minor but significant
      bronchoconstriction: the mean change (range) in postsalbutamol FEV1 (% pred) was 
      7 (-24-16). Percutaneous oxygen saturation remained above 90% in all children.
      The test had to be discontinued in one child because of cough and wheeze.
      Acceptability of the procedure evaluated using a visual analogue scale from -7-7
      showed a mean value (range) at the final concentration of -1.23 (-6.16-5.88). It
      is concluded that sputum induction is possible, safe and acceptable in cystic
      fibrosis children who do not expectorate spontaneously.

PMID- 10933092
TI  - Hydrogen peroxide and nitric oxide in exhaled air of children with cystic
      fibrosis during antibiotic treatment.
AB  - Cystic fibrosis (CF) patients characteristically have severe chronic airway
      inflammation associated with bacterial infection. A noninvasive marker of airway
      inflammation could be a useful guide to treatment of CF lung disease. The aim of
      this study was to assess whether measurement of hydrogen peroxide (H2O2) and
      nitric oxide (NO) in exhaled air can serve to monitor the effect of treatment
      with antibiotics in CF-children with acute infective pulmonary exacerbations.
      Sixteen CF-patients (mean age 12.3 yrs) with exacerbation of their lung infection
      were treated with intravenous antibiotics in an uncontrolled study. During
      treatment, H2O2 in exhaled air condensate was measured twice a week. In addition,
      serial NO measurements were performed in nine patients. During antibiotic
      treatment the median H2O2 concentration in exhaled air condensate decreased
      significantly from 0.28 microM (range 0.07-1.20 microM) to 0.16 microM (range
      0.05-0.24 microM, p=0.002) and the mean forced expiratory volume in one second
      significantly increased from 55% predicted to 75% pred (p=0.001). In individual
      subjects, changes of H2O2 and FEV1 between pairs of serial measurements
      correlated weakly (p=0.08). Data on exhaled NO were inconclusive; exhaled NO did
      not change systematically during treatment. It is concluded that cystic fibrosis
      patients with an acute pulmonary exacerbation have abnormally high concentrations
      of hydrogen peroxide, but not of nitric oxide, in exhaled air, which decrease
      during intravenous antibiotic treatment. Further controlled studies should
      establish if exhaled hydrogen peroxide, may serve as a noninvasive parameter of
      airway inflammation to guide antibiotic treatment in cystic fibrosis lung
      disease.

PMID- 10933094
TI  - Chlamydia pneumoniae infection in adults with chronic cough compared with healthy
      blood donors.
AB  - In a small uncontrolled study, persistent cough has recently been found to be
      associated with serological evidence of acute Chlamydia pneumoniae infection. In
      order to assess whether C. pneumoniae plays a role in chronic cough, the
      prevalence of C. pneumoniae infection in 201 adult patients with chronic cough
      was compared with the prevalence in 106 healthy blood donors without respiratory
      tract symptoms in the preceding 3 months. A microimmunofluorescence antibody test
      was used to determine C. pneumoniae antibodies in the immunoglobulin (Ig)M, IgG
      and IgA fractions. Further, nasopharyngeal aspirates from the 201 patients were
      examined for C. pneumoniae deoxyribonucleic acid by polymerase chain reaction
      (PCR). As judged by serology, nine patients (4%) and one control (1%) had acute
      C. pneumoniae infection, and 92 patients (46%) and 42 controls (40%) had previous
      or chronic C. pneumoniae infection. Of the nine patients with acute infection,
      three were C. pneumoniae PCR positive, and they all had an IgM antibody titre
      response. The remaining six patients had either an IgG antibody titre of > or
      =512 (five patients) or an IgA antibody titre of > or =512 (one patient). None of
      these six patients had detectable IgM antibodies. The mean cough period for the
      five IgG positive patients (10.8 weeks) was significantly longer than the mean
      cough period for the remaining patient population (6.4 weeks; p=0.004). It is
      concluded that Chlamydia pneumoniae infection was not statistically significantly
      more prevalent in patients with chronic cough than in healthy blood donors, and
      that Chlamydia pneumoniae appears to have a minor role in patients with chronic
      cough. Direct detection of Chlamydia pneumoniae by polymerase chain reaction on
      nasopharyngeal aspirates is highly correlated with detectable immunoglobulin M
      antibodies, but in the late stages of prolonged cough serological testing of
      immunoglobulin G and immunoglobulin A may be more beneficial for obtaining a
      microbiological diagnosis.

PMID- 10933093
TI  - Antenatal retinoic acid does not alter alveolization or postnatal lung function
      in preterm sheep.
AB  - Retinoic acid exposure has been shown to promote surfactant production in foetal
      rats and to promote alveolization in neonatal rats. It was hypothesized that
      antenatal retinoic acid treatment would promote alveolization and accelerate
      functional maturation in the lungs of late gestation preterm sheep. Foetuses
      received a single i.m. injection of all-trans retinoic acid (RA, 20 mg x kg(-1))
      or vehicle control at 115 days gestation (term=150 days) and were delivered at
      125 days gestation. To examine the longer term effects of RA on alveolization a
      second group of animals received RA or vehicle at 121 days gestation and were
      delivered at 146 days gestation. Liver retinol levels at time of delivery were 2
      3-fold higher in both preterm and near-term RA treated animals, indicating a
      significant impact of RA treatment on retinol metabolism. Dynamic compliance, gas
      exchange, lung gas volume and saturated phosphatidylcholine pool size at 125 days
      were unaffected by antenatal RA treatment. Alveolar volume, wall thickness and
      number at 125 or 146 days were also unaffected by RA treatment. Retinoic acid, as
      administered in this study, does not appear to accelerate structural or
      functional maturation of the foetal sheep lung. Response to retinoic acid may be
      species dependent, highlighting a need for caution when interpreting results from
      animal based studies.

PMID- 10933095
TI  - Antibacterial activity of human neutrophil peptide-1 against Mycobacterium
      tuberculosis H37Rv: in vitro and ex vivo study.
AB  - The aim of the study was to investigate the activity of human neutrophil peptide
      (HNP)-1 to kill Mycobacterium tuberculosis H37Rv in vitro and ex vivo in the
      murine macrophage cell line J744A.1 on the basis of colony forming units.
      Macromolecular biosynthesis was studied by monitoring the incorporation of
      radioactive precursors into different macromolecules. The binding and
      localization studies were carried out with radioiodinated HNP-1 whereas the
      cytotoxicity of HNP-1 to macrophages was determined by trypan blue exclusion
      assay. A concentration dependent inhibition in the growth of M. tuberculosis
      H37Rv was observed in the presence of HNP-1. The minimum inhibitory concentration
      and median inhibitory concentration of HNP-1 were found to be 2.5 microg x mL(-1)
      and 0.8 microg x mL(-1). Treatment of both in vitro grown and phagocytosed
      mycobacterial cells with HNP-1 resulted in generalized inhibition in the
      macromolecular biosynthesis with maximum inhibition in deoxyribonucleic acid and
      lipid biosynthesis. HNP-1 exhibited equilibrium binding with respect to time and
      two-thirds of bound radioactivity was shown to be present inside the macrophages.
      Approximately 50% and 98% killing of intracellular mycobacteria was observed
      after 3 days of treatment with 5 microg x mL(-1) and 40 microg x mL(-1) of HNP-1,
      respectively. HNP-1 exhibited low cytotoxicity towards the macrophage cell line
      at the bactericidal concentration to mycobacteria. From the results of this
      study, it is concluded that human neutrophil peptide-1 possesses potent
      bactericidal activity against virulent mycobacteria in vitro as well as
      mycobacteria replicating within macrophages.

PMID- 10933096
TI  - Long-term treatment with continuous positive airway pressure improves quality of
      life in obstructive sleep apnoea syndrome.
AB  - Continuous positive airway pressure (CPAP) is an established treatment of
      obstructive sleep apnoea syndrome (OSAS). While it is known that CPAP reverses
      the pathological breathing pattern and improves daytime sleepiness, there are no
      sufficient data on the long-term influence of CPAP on quality of life in patients
      with OSAS. Thirty-nine patients with polysomnographically verified OSAS
      (apnoea/hypopnoea index (AHI): (mean+/-SD) 46.8+/-21.8 events x h(-1)) were
      prospectively studied. All patients answered three quality of life measures
      (Complaint List, Nottingham Health Profile Part 1 (NHP), and Verbal Analogue
      Scale "quality of life") prior to the initiation of CPAP therapy. After a mean of
      9 months they were re-evaluated by polysomnography, and completed the
      questionnaires once again. As expected, CPAP was effective in treating the sleep
      related breathing disorder. AHI decreased significantly from (mean+/-SD) 46.8+/
      21.8 events x h(-1) to 3.3+/-6.3 events x h(-1), and minimum oxygen saturation
      increased from 77.1+/-9.3% to 89.9+/-3.4%, while body mass index did not change
      significantly (31.3+/-5.4 versus 30.8+/-4.8 kg x m(-2)). During long-term
      treatment with CPAP the Complaint List revealed a significant improvement of the
      extent of subjective impairment due to physical and general complaints (26.4+/
      9.9 versus 20.4+/-11.1), and NHP a significant improvement of emotional reactions
      (19.8+/-21.7 versus 11.1+/-14.0) and energy (50.8+/-36.6 versus 32.1+/-36.7), but
      not of pain, physical mobility, sleep, social isolation, and quality of life as
      assessed by the It is concluded that long-term continuous positive airway
      pressure therapy is effective in improving not only pathological breathing
      patterns but also parameters that estimate quality of life in patients with
      obstructive sleep apnoea syndrome.

PMID- 10933098
TI  - Cardiovascular risk factors in patients with obstructive sleep apnoea syndrome.
AB  - Cardiovascular disorders are common in patients with obstructive sleep apnoea
      syndrome (OSAS) but there is debate as to whether OSAS is an independent risk
      factor for their development, since OSAS may be associated with other disorders
      and risk factors that predispose to cardiovascular disease. In an effort to
      quantify the risk of OSAS patients for cardiovascular disease arising from these
      other factors, the authors assessed the future risk for cardiovascular disease
      among a group of 114 consecutive patients with established OSAS prior to nasal
      continuous positive airway pressure therapy, using an established method of risk
      prediction employed in the Framingham studies. Patients were 100 males, aged
      (mean+/-SD) 52+/-9.0 yrs, and 14 females, aged 51+/-10.4 yrs, with an
      apnoea/hypopnoea index of 45+/-22 x h(-1). Based on either a prior diagnosis, or
      a mean of three resting blood pressure recordings >140 mmHg systolic and/or 90
      diastolic, 68% of patients were hypertensive. Only 18% were current smokers,
      while 16% had either diabetes mellitus or impaired glucose tolerance, and 63% had
      elevated fasting cholesterol and/or triglyceride levels. The estimated 10-yr risk
      of a coronary heart disease (CHD) event in males was (mean+/-SEM) 13.9+/-0.9%,
      95% confidence interval (95% CI) 12.1-16.0, and for a stroke was 12.3+/-1.4%; 95%
      CI 9.4-15.1, with a combined 10 yr risk for stroke and CHD events of 32.9+/-2.7%;
      95% CI 27.8-38.5 in males aged >53 yrs. These findings indicate that obstructive
      sleep apnoea syndrome patients are at high risk of future cardiovascular disease
      from factors other than obstructive sleep apnoea syndrome, and may help explain
      the difficulties in identifying a potential independent risk from obstructive
      sleep apnoea syndrome.

PMID- 10933097
TI  - Evaluation of a portable respiratory recording device for detecting apnoeas and
      hypopnoeas in subjects from a general population.
AB  - This study was designed to validate a new home portable respiratory recording
      device (PRRD) to identify sleep apnoea and hypopnoea in a group of subjects
      (n=116), from a sample of the general population. Full night polysomnography
      (PSG) was used as the gold standard and simultaneously performed with PRRD. PRRD
      measurements included oronasal airflow (thermistry), chest wall impedance, oxygen
      saturation, snoring and body position. The sensors were unique for each recording
      system. Data obtained was blindly reviewed and analysed. A high level of
      agreement between both methods apnoea/hypopnoea index by PSG and the respiratory
      disturbance index (RDI) by PRRD was observed. Accuracy of the PRRD was evaluated
      in terms of sensitivity and specificity for different RDI-PRRD cut-off points
      with respect to AHI-PSG >10 and AHI-PSG >30. A logistic regression model was
      performed to estimate the chance per unit of RDI of apnoeas. A received operating
      characteristic (ROC) curve was drawn to obtain the sensitivity/specificity
      profile for each observed RDI value obtained. From the ROC curve the authors
      identified the better cut-off points, which represent a balanced
      sensitivity/specificity. Through a classification table defined by the cut-off
      point, the post-odds to exhibit the disease was calculated. For a full PSG cut
      off point of 10 a PRRD of six showed a balanced sensitivity of 95% and a
      specificity of 92%. For a full PSG cut-off point of 30 a PRRD of 16 shows a
      balanced sensitivity/specificity (100% and 97%, respectively). Post odds of
      apnoea were calculated for each cut-off point. In conclusion, these data suggest
      that the portable respiratory recording device is an effective device to identify
      apnoeas and hypopnoeas in a general population and is therefore a suitable device
      to be used in epidemiological studies.

PMID- 10933099
TI  - Bronchoscopy in the preoperative staging of oesophageal cancer below the tracheal
      bifurcation: a prospective study.
AB  - Oesophageal cancer located above the level of the tracheal bifurcation is
      frequently complicated by its spread into the airways and by the simultaneous
      occurrence of malignant bronchial tumours. Although bronchoscopy is an essential
      procedure in identifying malignant tumoral invasion of the airways and detection
      of primary airway tumours in patients with suprabifurcal oesophageal cancer, its
      role in patients with infrabifurcal oesophageal cancer is not clear. This study
      aimed to assess the value of fibreoptic bronchoscopy in the preoperative staging
      of oesophageal cancer located below the level of the tracheal bifurcation. In a
      prospective protocol, bronchoscopic findings were correlated with the results of
      other staging procedures, operative results and survival in 51 patients with
      oesophageal cancer located below the level of the tracheal bifurcation. One
      unsuspected primary bronchial cancer in a patient with squamous cell oesophageal
      cancer and one case of lower lobe invasion of an oesophageal adenocarcinoma were
      found. By excluding from surgery these two patients in whom curative resection
      was not possible bronchoscopy was the sole decisive staging investigation in 6.5%
      of potentially operable and 3.9% of all patients. Suspect macroscopic
      abnormalities were shown in 15.7% of the patients at bronchoscopy. Taking
      bronchoscopic biopsy as the gold standard the positive predictive value for all
      macroscopic abnormalities was only 25% (95% confidence interval (CI) 3.2-65.1%).
      The overall accuracy of bronchoscopy with biopsy and brush and washing cytology
      in proving or excluding airway invasion in otherwise potentially operable
      patients was 100% (95% CI 89.4-100%). Bronchoscopy is useful in the preoperative
      staging of oesophageal carcinoma located below the level of the tracheal
      bifurcation, particularly if the oesophageal cancer is of the squamous cell type.

PMID- 10933100
TI  - Cytokine release from the nasal mucosa and whole blood after experimental
      exposures to organic dusts.
AB  - The aim of this study was to assess the cytokine response after nasal exposure to
      organic dusts. In a double blinded, crossover study five garbage workers with
      occupational airway symptoms and five healthy garbage workers were intranasally
      exposed to endotoxin (lipopolysaccharide LPS), beta-1,3-D-glucan (GLU),
      Aspergillus sp., compost or the saline dilute for 15 min. Nasal cavity volume and
      nasal lavage (NAL) were performed at baseline and 3, 6, 11 h postexposure. NAL
      was analysed with differential cell counts, cysteinyl-leukotrienes, tumour
      necrosis factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A whole blood assay
      on cytokine-release was performed with LPS and GLU. NAL cytokines neutrophils,
      lymphocytes and albumin increased significantly at 6 h after LPS exposure. GLU
      induced an increase in albumin and a slight increase in IL-1beta 6-11 h post
      exposure. In the WBA a significant increase in all cytokines after exposure to
      LPS as well as GLU was found. Significantly more cells were seen in NAL of the
      control group 6 h post LPS exposure. In conclusion lipopolysaccharide is the most
      potent inducer of inflammation in the nasal mucosa whereas compost and beta-1,3-D
      glucan only induce minor changes. This reaction to lipopolysaccharide is
      attenuated in workers with occupational airway symptoms. In whole blood assay,
      however, beta-1,3-D-glucan also induces cytokine release, indicating a different
      protective effect of the nasal mucosa towards lipopolysaccharide and beta-1,3-D
      glucan.

PMID- 10933101
TI  - Endothelin-1 in stable bronchiectasis.
AB  - Endothelin (ET)-1 has been suggested to promote neutrophil adhesion to
      endothelium, migration to inflamed areas, and release of elastase. ET-1 might
      therefore play a role in the pathogenesis of bronchiectasis, a chronic
      inflammatory and infective airway disease which is still poorly understood.
      Thirty five patients with stable bronchiectasis (20 females, mean age+/-SD 49.1+/
      15.0 yrs) and 18 control subjects (8 females, 49.4+/-11.3 yrs) were recruited
      prospectively. The ET-1 levels in serum and sputum were measured by commercially
      available enzyme linked immunosorbent assay (ELISA) kits. Patients with
      Pseudomonas aeruginosa in their sputum had a significantly higher serum level of
      ET-1 (median 25.8, interquartile range 13-43.9 pg x mL(-1)) than patients without
      P. aeruginosa (0, 0-10.5 pg x mL(-1); p=0.0004) and healthy control subjects
      (4.6, 0-16.3 pg x mL(-1); p=0.002). However, patients with and without P.
      aeruginosa infection had no significant difference in sputum ET-1 level (p=0.15).
      There was no correlation between serum or sputum ET-1 levels with the serum and
      sputum levels of the interleukin (IL)-1beta, IL-8 and tumour necrosis factor
      (TNF)-alpha; the number of bronchiectasis lung lobes; and spirometry. Serum ET-1
      level correlated with 24 h sputum volume for the bronchiectasis patients (r=0.51,
      p=0.002). The results, therefore, suggest a significant pathogenic role for
      endothelin-1 among Pseudomonas aeruginosa-infected patients with bronchiectasis.
      Further studies should be performed to evaluate the clinico-pathological
      correlation and expression of endothelin-1 in bronchiectasis.

PMID- 10933102
TI  - Induced sputum cell counts: their usefulness in clinical practice.
AB  - Airway inflammation is fundamental to the aetiology and persistence of asthma and
      other airway conditions. The presence and type of airway inflammation can be
      difficult to detect clinically, delaying the introduction of appropriate
      treatment. Induced sputum cell counts are a relatively noninvasive, safe and
      reliable method of identifying airway inflammation. They can accurately
      discriminate eosinophilic airway inflammation from noneosinophilic airway
      inflammation, and help guide therapy. Eosinophilic airway inflammation is steroid
      responsive whilst noneosinophilic (usually neutrophilic) inflammation generally
      is not. Macrophages containing haemosiderin can be useful in detecting left
      ventricular dysfunction and macrophages containing lipid are suggestive of
      oropharyngeal reflux with microaspiration, both of which can complicate or
      confuse assessment of airway disease. To date, studies using induced sputum are
      primarily observational. Management studies based on examination of induced
      sputum are now needed to validate the clinical utility of this test.

PMID- 10933103
TI  - Phenotypic diversity and molecular mechanisms of airway smooth muscle
      proliferation in asthma.
AB  - Chronic persistent asthma is characterized by poorly reversible airflow
      obstruction and airways inflammation and remodelling. Histopathological studies
      of airways removed at post mortem from patients with severe asthma reveal marked
      inflammatory and architectural changes associated with airway wall thickening.
      Increased airway smooth muscle content, occurring as a result of hyperplastic
      and/or hypertrophic growth, is believed to be one of the principal contributors
      to airway wall thickening. In recent years, significant advances have been made
      in elucidating the mediators and the intracellular pathways that regulate
      proliferation of airway smooth muscle. The contribution that smooth muscle makes
      to persistent airflow obstruction may not, however, be limited simply to its
      increased bulk within the airway wall. Interest is growing in the possibility
      that reversible phenotypic modulation and increased heterogeneity of airway
      smooth muscle function may also be a feature of the asthmatic airway. This review
      focuses on possible mechanisms controlling smooth muscle phenotype heterogeneity
      as well as on the mediators and intracellular pathways implicated in its cellular
      proliferation. Particular attention is paid to mechanisms involving activation of
      the extracellular signal regulated kinase-, protein kinase C- and
      phosphoinositide 3-kinase-dependent pathways, since these appear to be the major
      candidate second messenger pathways for G protein- and tyrosine kinase-coupled
      receptor-stimulated proliferation.

PMID- 10933104
TI  - Scintigraphic comparison of budesonide deposition from two dry powder inhalers.
AB  - Chlorofluorocarbons (CFCs), used in metered dose inhalers (MDIs), have been
      identified as being deleterious to the environment leading to a ban on their
      production. Dry powder inhalers (DPIs) are a widely used alternative to MDIs. One
      disadvantage of DPIs is that in vivo lung deposition can be influenced by the
      patient's inspiratory flow rate. The ASTA Medica multi-dose dry powder inhaler
      (AM-MDPI) has been designed to offer low resistance on inhalation, so that
      asthmatic patients can achieve inhaled flow rates of approximately 90 L x min(
      1). The aim of the study was to evaluate the in vivo deposition of budesonide
      from the AM-MDPI at different flow rates and to compare this with delivery from a
      Turbuhaler DPI at a high flow rate. The study was a scintigraphic, randomized,
      crossover study in which 13 healthy volunteers inhaled a single 200 microg dose
      of radiolabelled budesonide on four separate occasions with a minimum 44-h
      washout period between dosings. At the lowest flow rate of 54 L x min(-1),
      comparable to that for the Turbuhaler (58 L x min(-1)), a similar percentage of
      the metered dose was delivered to the lung (AM-MDPI median 19.9%; Turbuhaler
      median 21.4%). At high flow rate (peak inspiratory flow rate 99 L x min(-1)) the
      AM-MDPI delivered significantly more drug to the lung (median 32.1% of metered
      dose) than at 65 L x min(-1) or 54 L x min(-1) (median 25.0% and 19.9% of metered
      dose, respectively), thus demonstrating flow rate dependence. The pattern of
      regional lung deposition from the AM-MDPI was similar for all three inhalation
      manoeuvres. It was concluded that the ASTA Medica multi-dose dry powder inhaler
      achieves at least as much deposition of budesonide in the lungs as a Turbuhaler
      when used at similar inspiratory flow rates.

PMID- 10933105
TI  - A patient with fatigue and subfebrile temperature.

PMID- 10933106
TI  - Chronic thromboembolic pulmonary hypertension and upper limb thrombosis.

PMID- 10933107
TI  - Circulating endothelin-1 and obstructive sleep apnoea.

PMID- 10933108
TI  - Joseph Lister: surgeon scientist (1827-1912).

PMID- 10933109
TI  - Surgically induced urologic models in swine.
AB  - The porcine urological system is similar anatomically and physiologically to that
      of humans. Swine have a true multirenculate, multipapillate kidney with a
      calyceal system like that of humans. The gross anatomic and histologic
      characteristics of the porcine and the human kidney are more similar than most
      other commonly used laboratory animals. The physiologic functions of the urinary
      system including urodynamic parameters are also similar to humans. Swine have
      been used extensively as models of urologic conditions in humans, most commonly
      in obstructive urologic syndromes. A large number of investigative procedures can
      be performed in one experiment both in acute and chronic models. Recently, a new
      technique of surgically induced antenatal lower urinary tract obstruction in
      swine has been developed.

PMID- 10933110
TI  - Effects of body temperature on accuracy of continuous cardiac output
      measurements.
AB  - Intermittent measurement of cardiac output is routine in the critically ill
      surgical patient. A new catheter allows real-time continuous measurement of
      cardiac output. This study evaluated the impact of body temperature variation on
      the accuracy of these measurements compared to standard intermittent bolus
      thermodilution technique. This prospective study in a university hospital
      surgical intensive care unit included 20 consecutive trauma patients. Data were
      collected with pulmonary artery catheters, which allowed both continuous (COC)
      and bolus (COB) thermodilution measurements. The catheter was placed through
      either the subclavian or internal jugular vein. Measurements for COB were
      performed using a bolus (10 cm3) of ice-cold saline with a closed-injectate
      delivery system at end-expiration. Computer-generated curves were created on a
      bedside monitor, and the average of three measurements within 10% of one another
      was used as COB. COC was determined as the average of the displayed CO before and
      after thermodilution CO measurements. Body temperature was measured from the
      pulmonary artery catheter and was grouped as < or =36.5 degrees C, 36.6-38.4
      degrees C, and > or =38.5 degrees C. COB and COC were compared for agreement by
      plotting the mean of the differences (COB - COC) between the methods. The
      differences were plotted against the average of each pair and analyzed with
      linear regression. One hundred seventy-eight paired measurements were made over a
      period of 1 to 3 days. CO ranged from 3.7 to 15.5 L/min. Eighty-one percent of
      measurements were at a temperature of 36.5-38.4 degrees C. Approximately 7% of
      measurements were at a temperature below 36.5 degrees C and 11.2% were in
      patients with a core temperature above 38.5 degrees C. Correlation between the
      two techniques was 0.96, 0.91, and 0.82 for temperatures of < or =36.5 degrees C,
      36.6-38.4 degrees C, and > or = 38.5 degrees C, respectively. In conclusion, the
      COC measurements correlate well with COB in trauma patients with a core
      temperature < or =38.5 degrees C. The accuracy degraded at higher temperatures,
      which may be related to the smaller signal-to-noise ratio at elevated body
      temperatures.

PMID- 10933112
TI  - Measurement of intracellular gamma-interferon, interleukin-4, and interleukin-10
      levels in patients following laparoscopic cholecystectomy.
AB  - Major surgery suppresses intracellular T-cell cytokine production. Laparoscopic
      surgery has been reported to have no effect on in vitro lymphocyte reactivity,
      but its effects on intracellular cytokine production are unknown. This study
      measured T-cell intracellular gamma-interferon, interleukin-4 (IL-4), and
      interleukin-10 (IL-10), along with serum interleukin-6 (IL-6) and cortisol
      levels, immediately before and 1 day after laparoscopic cholecystectomy in a
      cohort of six Air Force and veteran patients. Stimulated intracellular levels of
      gamma-interferon were slightly, but not significantly, elevated during the
      postoperative period in all T-cell subsets. There were no postoperative changes
      in stimulated IL-4 or IL-10 levels. Postoperative serum IL-6 levels, but not
      serum cortisol levels, were significantly elevated compared to preoperative
      values. In conclusion, laparoscopic surgery causes slight trauma but has no
      effect on T-cell intracellular interferon, IL-4, and IL-10 responses.

PMID- 10933111
TI  - Benzoporphyrin derivative monacid ring A (Verteporfin) alone has no inhibitory
      effect on intimal hyperplasia: in vitro and in vivo results.
AB  - Benzoporphyrin derivative monoacid ring A (Verteporfin, BPD-MA), a
      photosensitizing drug, has been suggested as having inhibitory effects on smooth
      muscle cell (SMC) proliferation in rabbit aortic intimal injuries. The effect of
      BPD-MA on vascular SMCs in the absence of light stimulation in vitro and in vivo
      was studied using models of intimal hyperplasia. Human SMCs were incubated with
      BPD-MA for 4 h in darkness. A small (20%) but significant decrease in viability
      (n =42,p < .05) was noted for BPD-MA concentrations above 15 microg/mL. This was
      an all-or-none phenomenon with no further decrease in viability at higher
      concentrations. Treatment with BPD-MA was also carried out in vivo using a
      balloon injury model of intimal hyperplasia in rabbit aortas. Thirty-three
      rabbits were randomized into five groups and given intravenous BPD-MA (2 mg/kg)
      according to the following schedule: Group 1 (n = 8), BPD-MA 25 min prior to
      injury; Group 2 (n = 8), BPD-MA 25 min prior to injury plus a second dose 4 weeks
      later; Group 3 (n = 4), BPD-MA immediately postinjury; Group 4 (n = 7), BPD-MA
      immediately postinjury plus a second dose 4 weeks later; or Group 5 (n = 6), no
      drug (control group). No statistically significant difference was seen in the
      amount of intimal hyperplasia that developed in the five groups.

PMID- 10933113
TI  - Effects of somatostatin analogues and vitamin C on bacterial translocation in an
      experimental intestinal obstruction model of rats.
AB  - The passage of viable endogenous bacteria and their products across the intact
      intestinal mucosal barrier, disseminating to the mesenteric lymph nodes,
      peritoneal cavity, spleen, liver, and circulation, is defined as bacterial
      translocation. Intestinal obstruction induces bacterial translocation due to
      mucosal disruption, motility dysfunction, and increased intestinal volume,
      leading to bacterial overgrowth. In a rat model of intestinal obstruction, the
      effects of both high-dose vitamin C (350 microg/kg), an antioxidant agent known
      to have a cytoprotective effect in ischemia-reperfusion injury, and somatostatin
      (20 microg/kg), a gastrointestinal antisecretory agent, in preventing bacterial
      translocation were studied. Both intestinal and liver samples from the rats was
      observed, and it was found that the rate of bacterial translocation was 100% in
      the control group, and only 43% for the rats who were given intraperitoneal
      vitamin C and somatostatin. The difference was statistically significant. In
      conclusion, we are convinced that vitamin C and somatostatin analogues may have
      protective effects against bacterial translocation in mechanical bowel
      obstruction.

PMID- 10933114
TI  - Role of Ritalin in preschoolers.

PMID- 10933115
TI  - 1999 Dennis P. Cantwell, M.D., Memorial Award.

PMID- 10933116
TI  - Mecamylamine in Tourette's syndrome: a two-year retrospective case study.
AB  - OBJECTIVE: To test the efficacy and safety of a nicotinic, acetylcholine
      antagonist, mecamylamine, in the treatment of Tourette's syndrome (TS). METHODS:
      This is a retrospective, open-label study of 24 patients; 18 of whom were not
      responding to accepted medication for treatment of their TS and six of whom were
      receiving no medication. All 24 of them received mecamylamine in 2.5-6.25 mgm/day
      dose, at varying starting dates during the years June 1997 to June 1999. There
      were four females, 20 males, with 19 patients under the age of 18 years and five
      over the age of 18. Efficacy was evaluated by the Clinical Global Impression
      Scale (CGI); safety by adverse events notes during the time mecamylamine was
      administered. RESULTS: The number of days each patient received mecamylamine
      varied from 8 days to 550 days; with nine patients more than 200 days, six
      patients from 100-200 days, five patients for 50-100 days, and four patients 0-50
      days. Comparing baseline CGI with that obtained on the date of last evaluation
      for each patient, a significant improvement in clinical assessment of severity of
      illness was obtained for the total group (Wilcoxon signed rank test, p < 0.0001).
      The six patients who received mecamylamine only also significantly improved
      (Wilcoxon signed rank test, p < 0.2). Case vignettes are described. CONCLUSIONS:
      Mecamylamine at 2.5-6.25 mgm/day has no significant peripheral parasympathetic
      activity and may be safely taken long term (up to 550 days in this study). It has
      a significant effect in relieving motor and vocal tics and in mood and behavior
      disturbances of children, adolescents, and adults with TS.

PMID- 10933117
TI  - Treatment of childhood-onset schizophrenia with olanzapine.
AB  - This paper reports on a clinical observation of 15 hospitalized youths ages 6-13
      years diagnosed with childhood-onset schizophrenia and acutely treated with
      olanzapine. Initial sedation was the most common side effect observed. Youngsters
      who had not had a previous trial on any psychotropic did better than those that
      had failed a previous medication trial. Age was inversely correlated with
      positive response to olanzapine. Patients who experienced initial sedation did
      best once the initial sedation wore off. The majority of patients in the study
      improved on olanzapine.

PMID- 10933118
TI  - Long-term risperidone for pervasive developmental disorder: efficacy,
      tolerability, and discontinuation.
AB  - To investigate the safety (e.g., weight gain, liver function, extrapyramidal side
      effects, and seizures) and efficacy of the long-term use of risperidone in
      children and adolescents and to ascertain the effects of drug withdrawal in a
      semi-naturalistic prospective, subjects with autism or pervasive developmental
      disorders not otherwise specified (PDDNOS) were treated with risperidone for 6
      months after which parents were given the option of continuing for a further 6
      months (final assessment at 12 months). Behavioral rating included Childhood
      Autism Rating Scale (CARS), Child Psychiatric Rating Scale (CPRS), Clinical
      Global Impression (CGI), and Child-Global Assessment Scale (C-GAS). Risperidone
      significantly ameliorated behavioral symptoms of PDD in 10 out of 11 subjects,
      with the effects on core symptoms being of smaller amplitude and of slower onset.
      No loss of effectiveness was observed in patients who continued risperidone for
      12 months, while a relapse of associated behavioral symptoms occurred in the
      others. Weight gain was common, although the rate of increase lessened over a
      period of time; after drug withdrawal, considerable weight loss was observed in
      the patient who had previously shown the most significant increase. After 6
      months of therapy, two patients developed facial dystonia: this disappeared after
      reducing dosage in one case, after drug discontinuation in the other. Amenorrhea
      was also observed, but no changes in liver function, blood tests or EEG were
      reported. The data indicate that risperidone is an effective and relatively safe
      drug for long term treatment of behavioral disruption in autistic children and
      adolescents.

PMID- 10933119
TI  - Efficacy and safety findings from naturalistic fluoxetine drug treatment in
      adolescent and young adult patients.
AB  - This article reports on the efficacy and safety of the selective serotonin
      reuptake inhibitor, fluoxetine, in 213 patients (ages 11-23 years) treated by
      psychiatrists/neurologists (PN) or general practitioners/internists (GPI). Data
      were derived from naturalistic drug utilization observation (DUO) studies with
      fluoxetine (n = 18,759 patients). Data collection--at the start and the end of
      the observation period (< or =6 weeks)--included patient characteristics,
      diagnoses, medication, co-medication, efficacy, and adverse events (AEs).
      Nonparametric statistics and descriptive p values (two-tailed) were used.
      Analyses revealed various differences between PN (n = 56) and GPI (n = 157)
      samples as to patient and treatment characteristics (p < 0.001-0.08). Based on
      both Clinical Global Impression (CGI; all p < 0.001) and self-assessment (total n
      = 47; Zung SDS, all p < or = 0.003), both PN and GPI patients showed improvements
      in their symptomatology over time, including suicidality (all p < 0.001; there
      were no group differences). Overall AE rates were higher in PN patients (p <
      0.01; 17.9% vs. 4.5%); the frequency and type of AEs in both subgroups were
      typical for fluoxetine and the total DUO samples. In fact, AE rates were lower
      compared to controlled trials. Findings suggest that PN patients were more
      severely ill at observation start and suffered a more complicated treatment
      course. However, clinical efficacy showed highly significant improvements in both
      subgroups; AE rates were low in both--although higher in PN patients. Thus,
      results support a positive benefit/risk ratio of fluoxetine use for this young
      patient population.

PMID- 10933120
TI  - An open trial of paroxetine in the treatment of children and adolescents
      diagnosed with dysthymia.
AB  - This open-label study examined the potential efficacy of paroxetine in the
      treatment of children and adolescents diagnosed with dysthymia over a period of 3
      months. Seven subjects were evaluated by the Hamilton Depression Rating Scale
      (HAM-D), by the Clinical Global Impression Severity of Illness Scale (CGI-S), and
      the Clinical Global Impression Improvement Scale (CGI-I). Seventy-one percent of
      patients had a satisfactory response, suggesting the efficacy of paroxetine in
      children with dysthymia.

PMID- 10933121
TI  - Does zinc moderate essential fatty acid and amphetamine treatment of attention
      deficit/hyperactivity disorder?
AB  - Zinc is an important co-factor for metabolism relevant to neurotransmitters,
      fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine
      metabolism, believed intimately involved in attention-deficit/hyperactivity
      disorder (ADHD). To explore the relationship of zinc nutrition to essential fatty
      acid supplement and stimulant effects in treatment of ADHD, we re-analyzed data
      from an 18-subject double-blind, placebo-controlled crossover treatment
      comparison of d-amphetamine and Efamol (evening primrose oil, rich in gamma
      linolenic acid). Subjects were categorized as zinc-adequate (n = 5), borderline
      zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell, and urine zinc
      levels; for each category, placebo-active difference means were calculated on
      teachers' ratings. Placebo-controlled d-amphetamine response appeared linear with
      zinc nutrition, but the relationship of Efamol response to zinc appeared U
      shaped; Efamol benefit was evident only with borderline zinc. Placebo-controlled
      effect size (Cohen's d) for both treatments ranged up to 1.5 for borderline zinc
      and dropped to 0.3-0.7 with mild zinc deficiency. If upheld by prospective
      research, this post-hoc exploration suggests that zinc nutrition may be important
      for treatment of ADHD even by pharmacotherapy, and if Efamol benefits ADHD, it
      likely does so by improving or compensating for borderline zinc nutrition.

PMID- 10933122
TI  - Structured interview and uniform assessment improves diagnostic reliability.
AB  - OBJECTIVE: To compare a Childhood Uniform Assessment Package (CUAP), including a
      computerized structured diagnosis, with routine assessment and treatment in
      public mental health settings. DATA SOURCES/STUDY SETTINGS: Data was collected
      prospectively on 250 children and adolescents in both public mental health
      inpatient and outpatient settings in a large metropolitan area and a rural area.
      STUDY DESIGN: Subjects were randomized to either routine assessment and treatment
      as usual (ATU) or ATU plus an additional "gold standard" assessment battery
      Childhood Uniform Assessment Package (CUAP). Outcome measures were taken at
      admission (baseline), discharge, and again 6 months later. METHODS: The study was
      conducted at a State Hospital (CUAP, n = 75; ATU, n = 75) and a Community Mental
      Health center (CUAP, n = 50; ATU, n = 50). The "gold standard" diagnostic process
      was established at the Children's Medical Center-Dallas. Research focused on a
      comparison of the CUAP diagnostic process to the existing diagnostic process
      (ATU) and the service delivery system of an inpatient and outpatient public
      sector clinical treatment setting. PRINCIPAL FINDINGS: A bachelor's level
      individual can be trained to administer a highly reliable diagnostic battery to
      meet a "gold standard," suggesting a possible cost-effective way to assist in
      diagnostic evaluations. Higher reliability was found between this standardized
      assessment package (CUAP) and inpatient physicians than for outpatient
      physicians. The highest interrater reliabilities were found for attention deficit
      and substance abuse disorders, less so for the other behavior disorders. The use
      of CUAP results in more reliable diagnoses in public settings than those provided
      by typical clinical staff by identifying mood and anxiety disorders (disorders
      with the lowest reliability) with better reliability. The addition of "gold
      standard" diagnostic assessments (CUAP) did not appear to affect length of stay,
      number of medication changes, use of seclusion or restraints, and other
      behavioral interventions in the inpatient setting. Outpatient follow-up services
      did not differ for CUAP versus ATU either. CONCLUSIONS: A standard uniform
      assessment package that includes a structured diagnostic instrument can improve
      overall diagnostic reliability but may not have a significant overall impact in
      clinical treatment strategies or outcomes without additional intervention to
      assure proper use of the information. A well-trained bachelor's level assistant
      can administer such a battery.

PMID- 10933123
TI  - Infection-triggered anorexia nervosa in children: clinical description of four
      cases.
AB  - BACKGROUND: Anorexia nervosa (AN) is a serious illness with no definitive
      treatment. Clinical and research evidence led to the hypothesis that some
      children with AN may have a pediatric autoimmune neuropsychiatric disorder
      associated with streptococcus (PANDAS), similar in pathogenesis to other
      hypothesized PANDAS disorders. METHODS: Four youngsters (ages, 11-15 years) with
      PANDAS AN were treated with an open trial of antibiotics, in addition to
      conventional treatment. They were evaluated for eating disorder and obsessive
      compulsive symptoms, and for weight gain. Evidence of streptococcal infection
      came from clinical evaluation, throat cultures, and two serological tests: anti
      deoxyribonuclease B (anti-DNase B) and anti-streptolysin O (ASO) titers. The
      "rheumatic" marker D8/17 was also measured. This B-cell alloantigen is
      associated, in several publications, with poststreptococcal autoimmunity:
      Rheumatic fever (RF), Sydenham's chorea (SC), and possibly PANDAS obsessive
      compulsive disorder (OCD) and tic disorders. RESULTS: There was clinical evidence
      of possible antecedent streptococcal infection in all four patients, two of whom
      had comorbid OCD, with possible infection-triggered AN. All four had the
      rheumatic marker: A percentage of D8/17-positive B cells of 28-38%, with a mean
      of 33% (12% or more is considered positive for the marker). The patients
      responded to conventional treatment plus antibiotics with weight restoration and
      decreased eating disorder and obsessive-compulsive symptoms. Three needed to gain
      weight and did so. CONCLUSIONS: There may be a link between infectious disease
      and some cases of AN, which raises the possibility of new treatment.

PMID- 10933124
TI  - Treatment of bipolar I disorder in an adolescent with olanzapine.
AB  - Bipolar I disorder is estimated to affect 0.6% of adolescents. Lithium, sodium
      valproate, carbamazapine, and adjunctive treatment with benzodiazapines and
      antipsychotics have been used to treat bipolar I disorders. We report a case of a
      17-year-old adolescent male with bipolar I disorder who responded favorably to
      the treatment with the atypical antipsychotic olanzapine. We hypothesize that
      olanzapine's broad affinity for both dopaminergic and serotonergic receptors may
      be related to the beneficial therapeutic outcome.

PMID- 10933125
TI  - Apolipoprotein A-I, cyclodextrins and liposomes as potential drugs for the
      reversal of atherosclerosis. A review.
AB  - Several studies have revealed that high-density lipoprotein (HDL) is the most
      reliable predictor for susceptibility to cardiovascular disease. Since
      apolipoprotein A-I (apoA-I) is the major protein of HDL, it is worthwhile
      evaluating the potential of this protein to reduce the lipid burden of lesions
      observed in the clinic. Indeed, apoA-I is used extensively in cell culture to
      induce cholesterol efflux. However, while there is a large body of data emanating
      from in-vitro and cell-culture studies with apoA-I, little animal data and scant
      clinical trials examining the potential of this apolipoprotein to induce
      cholesterol (and other lipid) efflux exists. Importantly, the effects of
      oxysterols, such as 7-ketocholesterol (7KC), on cholesterol and other lipid
      efflux by apoA-I needs to be investigated in any attempt to utilise apoA-I as an
      agent to stimulate efflux of lipids. Lessons may be learnt from studies with
      other lipid acceptors such as cyclodextrins and phospholipid vesicles (PLVs,
      liposomes), by combination with other effluxing agents, by remodelling the
      protein structure of the apolipoprotein, or by altering the composition of the
      lipoprotein intended for administration in-vivo. Akin to any other drug, the
      usage of this apolipoprotein in a therapeutic context has to follow the
      traditional sequence of events, namely an evaluation of the biodistribution,
      safety and dose-response of the protein in animal trials in advance of clinical
      trials. Mass production of the apolipoprotein is now a simple process due to the
      advent of recombinant DNA technology. This review also considers the potential of
      cyclodextrins and PLVs for use in inducing reverse cholesterol transport in-vivo.
      Finally, the potential of cyclodextrins as delivery agents for nucleic acid-based
      constructs such as oligonucleotides and plasmids is discussed.

PMID- 10933126
TI  - Body distribution of poly-DL-lactide-poly(ethylene glycol) microspheres with
      entrapped leptospira interrogans antigens following intravenous and oral
      administration to guinea-pigs.
AB  - Poly-DL-lactide-poly(ethylene glycol) (PELA) microspheres with entrapped antigens
      were administered intravenously and orally into guinea-pigs to quantitatively
      determine the in-vivo distribution and release profiles. PELA microspheres
      containing 125I-labelled outer-membrane protein Leptospira interrogans antigens
      (125I-OMP) were prepared by double-emulsion solvent extraction procedure, and
      characterized with respect to size, morphology and in-vitro release profiles. The
      fractured sections of liver and spleen were inspected by scanning electron
      microscopy, which indicated that microspheres had successfully been entrapped
      within the above tissues after intravenous injection and oral administration. At
      predetermined intervals, the blood and such tissues as the liver, spleen, kidney,
      thyroid, small intestine and mesentery were collected, and the radioactivity was
      measured by gamma scintillation counting. Following intravenous administration,
      56.7% of administered microspheres were accumulated in immunization-related
      tissues, and 40.1% of microspheres were located in the liver and spleen. However,
      there was limited uptake efficiency (8.33%) following oral administration, and
      49.5% of the absorbed microspheres were located in the intestinal mucosa.
      Compared with in-vitro release, the in-vivo release profiles of 125I-OMP from
      PELA microspheres, determined from the decreasing radioactivity in the above
      tissues, were much faster and the burst effect was higher. Antigen-loaded PELA
      microspheres were efficiently entrapped within immunization-related tissues after
      intravenous administration, but orally administered PELA microspheres showed
      limited uptake efficiency. Further investigation is needed to improve intestinal
      absorption.

PMID- 10933127
TI  - A human oral-throat cast integrated with a twin-stage impinger for evaluation of
      dry powder inhalers.
AB  - The aim of this study was to investigate the applicability of replacing the glass
      throat from a twin-stage impinger (TSI) with a human oral-throat cast.
      Monodisperse aerosols were used to calibrate the human oral cast-TSI at 60 L min(
      1) and cut-off in particle size was compared with that of the TSI described in
      the British Pharmacopoeia which employs a glass throat. The amount of salbutamol
      sulphate (and lactose) delivered by the Cyclohaler depositing on various elements
      of the in-vitro model were determined. The calibration of the model containing a
      human oral-throat cast at 60 L min(-1) gave a particle size cut-off of 5.2 microm
      which was less than that of the TSI (6.3 microm). The oral-throat cast trapped
      more drug than the glass throat model with a formulation that employed the larger
      carrier (63-90 microm; P<0.05) while it trapped a lesser amount of drug with
      those filled with the lower size carrier (Lactochem, micronised lactose). The
      greater amount of lactose in the formulation that employed the larger-sized
      carrier (63-90 microm) was deposited closer to the inlet of the oral-throat cast
      than to the inlet of the glass throat model. Replacement of the glass throat in
      the TSI by the human oral-throat cast, leads to a change in deposition
      efficiency, with the cast having a higher filter efficiency and hence more
      aerosol particles being captured before their entry into the TSI. This should be
      investigated further to determine whether such a model might provide a more
      realistic assessment of the in-vivo characteristics of an aerosol in comparison
      with the TSI currently being employed, which utilises the glass throat as the
      portal of entry.

PMID- 10933128
TI  - Cytotoxicity and teratogenicity of chlorhexidine diacetate released from hollow
      nylon fibres.
AB  - Intra-uterine contraceptive devices are associated with an increased incidence of
      pelvic infections, possible due to the introduction of vaginal bacteria into the
      uterus at insertion. One potential means to overcome this problem is the use of a
      device which releases the antimicrobial agent chlorhexidine although such an
      approach carries with it the risk of adverse effects on the endometrium and,
      possibly, teratogenic effects. Cultured monolayers of endometrial cells were used
      to assess the cytotoxicity of both chlorhexidine and chlorhexidine-releasing
      devices. The results indicated that the agent is toxic at concentrations of 1
      microg mL(-1) and that the devices potentiated the toxicity. When the devices
      were tested in a guinea-pig model, endometrial damage was seen only at the high
      dose of chlorhexidine, suggesting that there is greater distribution of
      chlorhexidine in-vivo. Assessment of the teratogenic effects of chlorhexidine in
      rat embryonic limb bud tissue cells in-vitro showed that the foetal cells were
      highly susceptible to the toxic effects of chlorhexidine, but that there was no
      evidence of teratogenicity. Overall, the findings suggest that chlorhexidine
      releasing devices may be a safe means of reducing infections related to intra
      uterine devices, but that the chlorhexidine may have a toxic effect on foetal
      cells.

PMID- 10933130
TI  - Recombinant factor VIII SQ--stability of VIII: C in homogenates from porcine,
      monkey and human subcutaneous tissue.
AB  - The aim of this paper was to investigate whether a formulation-based approach to
      understanding and addressing stability could generate a subcutaneous factor VIII
      preparation for patients as an alternative to the existing intravenous products.
      The low bioavailability of subcutaneously administered factor VIII could have
      several causes: proteolytic degradation of the protein in the interstitium;
      adsorption to tissue, in particular to acidic phospholipids such as L-alpha
      phosphatidyl-L-serine (phosphatidylserine); the absence of free von Willebrand
      factor in the interstitium; phagocytosis by macrophages in the interstitium or in
      the lymph nodes; and coagulation could be initiated upon injection. This study
      was undertaken to investigate the first three factors in-vitro (i.e., proteolytic
      degradation, adsorption to tissue and the protective effect of von Willebrand
      factor). The influence of some other macromolecular stabilisers and protease
      inhibitors was also investigated. The stability of factor VIII activity (VIII: C)
      was investigated in homogenates from porcine, monkey and human subcutaneous
      tissue. Possible coagulation was prevented in these studies by the presence of
      both citrate and antithrombin. An exploratory in-vivo study was performed in the
      pig; plasma samples were assayed with a factor VIII:Ag (90kDa) ELISA. The
      decrease in VIII:C appeared to be more pronounced in homogenates from monkey and
      human tissues than in porcine homogenate. The results from human tissue
      homogenate resembled the degradation profile seen in monkey homogenate. Both the
      von Willebrand factor and phosphatidylserine/phosphatidylcholine (PS/PC)
      liposomes showed a significant stabilising effect on VIII:C in the tissue
      homogenates. The qualitative pattern was similar in porcine, monkey and human
      tissue. A combination of several protease inhibitors seemed to have a protective
      effect on the stability of VIII: C albeit at high concentrations of inhibitors
      and the effect was less than that of PS/PC. An exploratory in-vivo study was
      performed in the pig with phosphatidylserine in two formulations; either in the
      form of PS/PC liposomes or together with Polysorbate 80 in the form of mixed
      micelles (phosphatidylserine/P80). Including phosphatidylserine in the
      formulations appeared to increase the availability, of subcutaneously
      administered r-VIII SQ in the pig. However, further studies are necessary,
      preferably in the monkey where in-vitro studies indicate a closer resemblance to
      the human. In conclusion, a proposed inactivation mechanism for r-VIII SQ in
      subcutaneous tissue could be adsorption to phospholipid surfaces followed by
      proteolytic degradation. However, additional studies are required due to the
      multitude of factors influencing the subcutaneous absorption route. A combination
      of protease inhibitor(s) together with phosphatidylserine-containing liposomes
      are suggested for further investigation, preferably in a monkey animal model.

PMID- 10933129
TI  - Investigations of the in-vitro metabolism of three opioid tetrapeptides by
      pancreatic and intestinal enzymes.
AB  - The metabolism of three opioid tetrapeptides, Tyr-D-Arg-Phe-Nva-NH2, Tyr-D-Arg
      Phe-Phe-NH2 and Tyr-D-Ala-Phe-Phe-NH2, was investigated in the presence of pure
      pancreatic enzymes (trypsin, chymotrypsin, elastase, carboxypeptidase A and
      carboxypeptidase B), as well as in the presence of pure carboxylesterase and
      aminopeptidase N. The cleavage patterns of the pure pancreatic enzymes were then
      compared with those found in rat and human jejunal fluid. Metabolism was also
      studied in homogenates from different intestinal regions (duodenum, jejunum,
      ileum and colon) and in enterocyte cytosol from rats. The effect of various
      protease inhibitors was investigated in the jejunal homogenate. The parent
      peptides were assayed by high-performance liquid chromatography and metabolites
      were identified by means of liquid chromatography-mass spectrometry. Of the pure
      enzymes, the quickest hydrolysis of the peptides was observed for the pancreatic
      enzymes chymotrypsin, trypsin and carboxypeptidase A. In most cases they formed
      the corresponding deamidated tetrapeptides (chymotrypsin and trypsin) or
      tripeptides with a missing C-terminal amino acid (carboxypeptidase A). Regional
      differences in intestinal metabolism rates were found for all three peptides (P <
      0.001), with the highest rates observed in jejunal and/or colonic homogenates.
      The deamidated tetrapeptides were formed both in rat intestinal homogenates and
      in enterocyte cytosol. Metabolism in the jejunal homogenate was markedly
      inhibited by some serine and combined serine and cysteine protease inhibitors. In
      conclusion, the C-terminal amide of these tetrapeptides did not fully stabilise
      them against intestinal deamidase and carboxypeptidase activities. The
      significant hydrolysis of the peptides by pure chymotrypsin, trypsin and
      carboxypeptidase A showed that lumenal pancreatic proteases might be a clear
      metabolic obstacle in oral delivery even for small peptides such as these
      tetrapeptides.

PMID- 10933131
TI  - Intravenous formulations of the enantiomers of thalidomide: pharmacokinetic and
      initial pharmacodynamic characterization in man.
AB  - Thalidomide, a racemate, is coming into clinical use as an immunomodulating and
      antiinflammatory drug. These effects may chiefly be exerted by S-thalidomide, but
      the enantiomers are interconverted in-vivo. Thalidomide is given orally, although
      parenteral administration would be desirable in some clinical situations. The aim
      of this study was to prepare solutions of the enantiomers of thalidomide for
      intravenous administration and to investigate their pharmacokinetics and sedative
      effects following infusion in man. Solubility and stability of the enantiomers in
      5% glucose solution was investigated. After a dose-determination experiment in
      one subject, six healthy male volunteers received R- and S-thalidomide separately
      by 1-h infusions in a randomized double-blind cross-over study. Blood was sampled
      over 22h and sedative effects were recorded. Blood concentrations of the
      enantiomers were determined by stereospecific HPLC. A four-compartment model
      consisting of a two-compartment model for each enantiomer, with elimination from
      both compartments, connected by rate constants for chiral inversion was fitted to
      the concentration data, while the sedative effects were correlated with the blood
      concentrations of R- and S-thalidomide by means of logistic regression. The
      enantiomers of thalidomide were chemically stable in solution for at least a week
      at room temperature. The infusions were well tolerated. Sedation, which was the
      only observed effect, was related to the blood concentration of R-thalidomide.
      Inter-individual variation in the disposition of the enantiomers was modest (e.g.
      terminal half-lives ranged between 3.9 and 5.3h). Pharmacokinetic modelling
      predicted that varying the infusion time of a fixed dose of S-thalidomide between
      10 min and 6h would have little influence on the maximal blood concentration of
      formed R-thalidomide. To our knowledge this is the first time that thalidomide
      has been administered intravenously.

PMID- 10933132
TI  - Isolation and identification of three potential impurities of pholcodine bulk
      drug substance.
AB  - Three previously unreported manufacturing impurities were isolated from a
      pholcodine mother liquor using preparative reversed-phase HPLC. The liquor was
      the residue remaining after recrystallisation of a production batch of
      pholcodine. The impurities, which are structurally related to pholcodine, were
      initially detected by thin-layer chromatography (TLC). Their structures were
      determined after separation by preparative HPLC (Econo-Prep 5 microm C18 column,
      30 cm x 21.2 mm i.d.). Structure elucidation was carried out using nuclear
      magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and ultra violet
      (UV) spectroscopy. The impurities were identified as alkylated derivatives of
      pholcodine possessing second 2-morpholinoethyl substituents at various positions.

PMID- 10933133
TI  - In-vitro in-vivo correlation models for glibenclamide after administration of
      metformin/glibenclamide tablets to healthy human volunteers.
AB  - In this study, level C and A in-vitro in-vivo correlation (IVIVC) models were
      developed for glibenclamide. In-vitro dissolution data were collected for the
      glibenclamide component of three metformin/glibenclamide tablets using a USP Type
      II apparatus. In-vivo plasma concentration data were obtained after
      administration of the prototype formulations to 24 healthy volunteers and subject
      to deconvolution analysis to obtain percentage in-vivo absorbed profiles.
      Multiple linear level C models were developed for CMAX and AUC(0-48) using
      percentage in-vitro dissolved data at 10, 45 and 120 min. Initially, the level A
      model was constructed for the first 2 h only, based on availability of in-vitro
      data. Another level A model was attempted using a time-scaled approach, with
      percentage in-vivo absorbed at time t and percentage in-vitro dissolved at time
      t/I as the correlating data. Internal predictability was evaluated for the level
      C and time-scaled level A models. For all level C approaches, linear regression
      models with r2 > 0.99 were determined. The prediction errors (% PE) for Cmax and
      AUC(0-48) were less than 1% for all formulations at all three chosen time points.
      The deconvolution analysis indicated biphasic absorption for glibenclamide, with
      one phase occurring at 2-3h and another at 6-12h after dose administration. The
      level A model using 2-h data was not unique for all formulations and was
      therefore not developed. The time-scaling factor I correlated highly (r2 = 0.99)
      with in vitro mean dissolution time (MDT). A linear regression time scaled model
      (r2 = 0.97) was successfully developed using in-vitro and in-vivo data from all 3
      formulations. However, the internal predictability of the time-scaled model was
      poor, with % PE values for Cmax and AUC(0-48) being as much as 30.5% and 18.7%,
      respectively. The results indicate that level C models have good internal
      predictability. Though a time-scaled level A IVIVC model was successfully
      developed, the model was found to have poor internal predictability.

PMID- 10933134
TI  - Structure-activity relationships of anthraquinones in the decrease of intestinal
      motility.
AB  - The effects of substituted anthraquinones on intestinal motility were evaluated
      in-vitro using rabbit small intestinal strips. This structure-activity
      relationship study revealed the critical requirement of a hydroxy group at R2
      position. The intestinal motility was inhibited 50% (IC50) by emodine (8 microM),
      2-hydroxy anthraquinone (20 microM), 2,6-dihydroxy anthraquinone (25 microM), 2,7
      dihydroxy anthraquinone (10 microM), 1,2,4-trihydroxy anthraquinone (80 microM)
      and 1,2,5,8-tetra-hydroxyanthraquinone (9 microM). The presence of other polar
      groups at R2 position such as an amino, aldehyde and carboxylic acid group
      significantly reduced the activity (IC50 360-400 microM). The presence of a
      methyl group and esterification of the carboxylic acid at R2 position was found
      to abolish the activity. These data are useful for the future development of
      anthraquinones as laxative agents.

PMID- 10933135
TI  - The effect of progesterone on spontaneous and agonist-evoked contractions of the
      rat aorta and portal vein.
AB  - The mechanisms underlying the suppression of vasocontractility caused by
      progesterone were investigated by studying changes in the contractile force of
      rat isolated aorta and portal vein, induced by altering extracellular
      concentrations of noradrenaline (NA) potassium ions (K+) and calcium ions (Ca2+).
      In the aorta, progesterone (10 microM) had a general suppressive effect on NA-,
      Ca2+- and K+-induced contractions. In contrast, in the portal vein a more
      selective suppression of contractions was observed. Both tonic and phasic
      components of contractions induced by cumulative addition of Ca2+ to tissues
      equilibrated in Ca2+-free saline were suppressed. The phasic but not tonic
      components of contractions induced by NA addition were suppressed. There was no
      significant effect on tonic contractions induced by elevated (40-120 mM) K+, but
      a concentration-dependent suppression of the phasic component of contractions was
      observed during depolarisation with smaller elevations of K+ concentrations (5-20
      mM). These results suggest that on the portal vein the suppressive effect of
      progesterone is due to a potassium channel opening action, whilst on the aorta a
      different or additional mechanism of suppression exists.

PMID- 10933136
TI  - Effects of the oral administration of a beta3-adrenergic agonist on lipid
      metabolism in alloxan-diabetic rats.
AB  - Previous studies have reported that beta3-adrenergic agonists regulate plasma
      glucose, triglycerides and free fatty acids in situations of hyperglycaemia and
      dyslipidaemia in rodents. In this study Trecadrine, a novel compound with
      affinity for beta3-adrenergic receptors, has been tested in an alloxan-induced
      model of hyperglycaemia in rats. Alloxan-induced hyperglycaemic rats were orally
      treated with Trecadrine (1 mg/kg/day for 4 days), resulting in an improvement of
      hyperglycaemia (from 16.6 to 8.3 mmol L(-1), P < 0.001). This effect was not
      associated with statistical differences in plasma insulin levels, which may be
      explained by changes in insulin resistance and carbohydrate oxidation in
      peripheral tissues. Furthermore, a reduction in internal white fat weight (-39%),
      which was not statistically significant, as well as in plasma triglycerides (from
      1.89 to 0.33 mmol L(-1), P < 0.001) and free fatty acids (from 0.70 to 0.39 mmol
      L(-1), P < 0.001), was found after Trecadrine administration. Trecadrine
      apparently induced lipolytic activity in adipocytes, as suggested by the increase
      of oxygen consumption in white adipose tissue (+282%, P < 0.001), while free
      fatty acids decreased apparently through their utilisation in other tissues.
      Furthermore, the increase in brown adipose tissue oxygen consumption (+50%, P <
      0.01) and in rectal temperature (P < 0.05) suggests that both glucose and fatty
      acid oxidation may be enhanced in this tissue. These results give support to the
      possible therapeutic use of beta3-adrenergic compounds in situations of
      hyperglycaemia, particularly when this is accompanied by hypertriglyceridaemia.

PMID- 10933137
TI  - Inhibition of vascular smooth muscle tone by the H+, K+-ATPase inhibitor SCH
      28080.
AB  - Vascular smooth muscle is thought to possess an H+-K+ ATPase that contributes to
      the regulation of intracellular K+ concentration and pH. We have examined the
      effect of the H+, K+-ATPase inhibitor SCH 28080 on vascular smooth muscle tone in
      guinea-pig and human isolated arteries, and on 86Rb+ uptake in cultured guinea
      pig aortic smooth muscle cells. SCH 28080 (0.1-300 microM) produced relaxation of
      isolated guinea-pig aorta, guinea-pig pulmonary artery and human pulmonary
      artery. Relaxation occurred in tissues pre-contracted with phenylephrine,
      histamine or the thromboxane mimetic U44069. Relaxation. was reversible, and was
      not affected by tetrodotoxin, indomethacin, nordihydroguiaretic acid (NDGA), 1
      aminobenzotriazole (1-ABT), N(G)-nitro-L-arginine methyl ester (L-NAME), removal
      of the endothelium or removal of extracellular K+. SCH 28080 had no effect on
      86Rb+ uptake in cultured guinea-pig aortic smooth muscle cells. In conclusion,
      SCH 28080 relaxes vascular smooth muscle at concentrations known to inhibit the
      H+-K+ ATPase. The persistence of relaxation in a K+-free medium and the failure
      of SCH 28080 to inhibit 86Rb+ uptake suggest that relaxation may be unrelated to
      H+, K+-ATPase inhibition, and indicate that this agent may not be considered as a
      selective H+, K+-ATPase inhibitor in vascular preparations.

PMID- 10933138
TI  - Effect of iron(III) chitosan intake on the reduction of serum phosphorus in rats.
AB  - Because of the widespread use of aluminium- and calcium-containing phosphate
      binders for the control of hyperphosphataemia in patients with end-stage renal
      failure, an iron(III) chitosan complex was synthesised and fed to rats to measure
      its effect on serum phosphorus and calcium, intestinal phosphate binding and
      phosphate absorption. Thirty-six Wistar rats were randomly selected and
      distributed into a baseline group (n = 6), a control group (n = 8 (days 0-15), n
      = 8 (days 16-30)) and a treatment group (n = 8 (days 0-15), n = 8 (days 16-30)).
      The control groups ingested AIN-76 diet mix with a 1% w/w fibre content; however,
      the treatment groups had the fibre content completely substituted with iron(III)
      chitosan. The mean weights of the treated rats were slightly lower from 15 days
      (not significant); but overall, rat growth was not stunted in the treatment
      groups. The serum phosphorus levels of the treated group (n = 8) were
      significantly reduced after 15 days (P = 0.004; control: 5.7+/-0.9 mg dL(-1);
      treatment: 4.4+/-0.5 mg dL(-1); 95% CI of difference: 0.5-2.2) and 30 days (P =
      0.002; control: 5.5+/-0.9 mg dL(-1); treatment = 4.1+/-06 mg dL(-1); 95% CI of
      difference: 0.6-2.3) as compared with the respective control group. The serum
      calcium-phosphorus product was 62.0+/-12.1 mg2 dL(-2) for the control and 45.1+/
      6.6 mg2 dL(-2) for the treatment group after 30 days (P = 0.004). The serum iron
      concentration of the treatment group did not differ from the baseline value after
      15 and 30 days, but the treatment group was significantly higher than the control
      group (P<0.05) after 30 days. The faeces phosphorus levels (mg day(-1)) were
      higher (P<0.01) and its iron content was much higher (P<0.01) for the treated
      group. The urine phosphorus (mg kg(-1)) was not significantly reduced for the
      treated group, but the mean was consistently less. The kidney and liver weights
      of both groups were similar, but the phosphorus content of the kidney (mg (g
      kidney)(-1)) was higher for the treated group after 30 days (P = 0.041; control,
      4.2+/-1.2 mg g(-1) vs treatment, 5.6+/-1.4 mg g(-1). Because iron(III) chitosan
      had a high phosphorus-binding capacity of 308 (mg P) per gram of Fe3+ for both
      the in-vitro (pH 7.5) and in-vivo studies, which is greater than nearly all
      commonly used phosphate binders, and a small net phosphorus absorption difference
      of 3.7 mg day(-1), it is an efficient phosphate binder for lowering serum
      phosphate levels without increasing serum calcium levels.

PMID- 10933139
TI  - The ethanol-soluble part of a hot-water extract from Artemisia iwayomogi inhibits
      liver fibrosis induced by carbon tetrachloride in rats.
AB  - This study was carried out to investigate the protective effects of the hot-water
      extract from Artemisia iwayomogi (Compositae) on carbon tetrachloride-induced
      liver fibrosis in rats. Liver injury was induced by oral administration of carbon
      tetrachloride (1 mL kg(-1)) twice a week during 4 weeks of A. iwayomogi
      treatment. Extracts from A. iwayomogi were prepared and administered to rats
      orally (2 g kg(-1) as A. iwayomogi for 4 weeks) as follows: group 1, hot-water
      extract; group 2, ethanol-soluble part of hot-water extract; group 3, ethanol
      insoluble part of hot-water extract; and group 4, methanol extract. In rats
      treated with the ethanol-soluble part of the hot-water extract, liver
      hydroxyproline content was reduced to 74% that of carbon tetrachloride control
      rats (P < 0.05). Protein expression of alpha smooth muscle cell like actin was
      also decreased in rats treated with the ethanol-soluble part of the hot-water
      extract, which indicates inhibition of hepatic stellate cell activation. Liver
      malondialdehyde levels were significantly lowered in rats treated with the
      ethanol-soluble part of hot-water extract (P < 0.05). Serum cholesterol levels in
      rats treated with hot-water extract, ethanol-soluble or -insoluble parts of hot
      water extract or methanol extract were significantly reduced when compared with
      those of carbon tetrachloride control rats (P < 0.05). The ethanol-soluble part
      of the hot-water extract from A. iwayomogi inhibited fibrosis and lipid
      peroxidation in rats with liver fibrosis induced by carbon tetrachloride. Both
      hot-water extract (either ethanol-soluble or -insoluble) and methanol extract of
      A. iwayomogi also lowered serum cholesterol levels in fibrotic rats.

PMID- 10933140
TI  - Antitumour activity and side effects of combined treatment with chitosan and
      cisplatin in sarcoma 180-bearing mice.
AB  - We examined the possible modulation by chitosan of the antitumour effects and
      side effects of cisplatin (cis-diaminedichloroplatinum, CDDP). The study showed
      that CDDP had potent antitumour activity when administered orally as well as
      intraperitoneally. We also compared the antitumour activity and side effects of
      orally administered CDDP plus orally administered chitosan versus
      intraperitoneally administered CDDP plus orally administered chitosan in sarcoma
      180-bearing mice. When CDDP (1.25 mgkg(-1) x 2 day(-1)) was intraperitoneally
      administered to sarcoma 180-bearing mice, myelotoxicity (the reduction of
      leucocyte and platelet numbers), nephrotoxicity (the increase of blood nitrogen
      urea level), immunotoxicity (the reduction of spleen and thymus weight) and a
      reduction in body weight resulted. These intraperitoneally administered CDDP
      induced side effects were not prevented by oral administration of chitosan (150
      mgkg(-1) x 2 day(-1) and 750 mgkg(-1) x 2 day(-1)) for 14 consecutive days. On
      the other hand, the side effects such as the reductions of body and spleen
      weights induced by orally administered CDDP (1.25 mgkg(-1) x 2 day(-1)) were
      prevented by the oral administration of chitosan (150 mgkg(-1) x 2 day(-1) and
      750 mg kg(-1) x 2 day(-1)). From these results, we conclude that the orally
      administered chitosan plus CDDP might be useful for the prevention of body weight
      reduction and immunotoxicity (the reduction of spleen weight) induced by the
      orally administered CDDP without diminishing antitumour activity.

PMID- 10933141
TI  - Effect of Luffa echinata on lipid peroxidation and free radical scavenging
      activity.
AB  - The dried alcoholic (50%) extract of the plant Luffa echinata was investigated
      for inhibition of lipid peroxidation, for hydroxyl radical scavenging activity
      and interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). It
      was found that the test extract exhibited a considerable inhibition of lipid
      peroxidation and possessed hydroxyl radical scavenging activity. Evaluation of
      antiradical scavenging activity showed significant interaction with DPPH. These
      properties could be considered as a useful and exploitable combination for
      justifying the reported activity.

PMID- 10933142
TI  - In-vitro inhibition of human erythrocyte acetylcholinesterase by salvia
      lavandulaefolia essential oil and constituent terpenes.
AB  - Sage (Salvia spp) is reputed in European herbal encyclopaedias to enhance memory,
      and current memory-enhancing/anti-dementia drugs are based on enhancing
      cholinergic activity by inhibiting cholinesterase. In this study the effects of
      Salvia lavandulaefolia Vahl. (Spanish sage) essential oil and some of its
      constituent terpenes on human erythrocyte acetylcholinesterase were examined in
      vitro. The main constituents in the essential oil batch used for analysis of
      cholinesterase inhibition were camphor (27%), 1,8-cineole (13%), alpha- and beta
      pinene (10-15%) and bornyl acetate (10%) with other minor constituents (1% or
      less) including geraniol, limonene, linalool, terpineol and gamma-terpinene.
      Using the Ellman spectrophotometric method, kinetic analysis was conducted on the
      interaction of the essential oil and the main monoterpenoids, camphor, 1,8
      cineole and alpha-pinene. IC50 values were obtained for the essential oil, 1,8
      cineole and alpha-pinene and were 0.03 microL [corrected] mL(-1), 0.67 mM and
      0.63 mM, respectively. Camphor and other compounds tested (geraniol, linalool and
      gamma-terpinene) were less potent (camphor IC50: >10mM). The essential oil, alpha
      pinene, 1,8-cineole and camphor were found to be uncompetitive reversible
      inhibitors. These findings suggest that if the inhibitory activity of the
      essential oil is primarily due to the main inhibitory terpenoid constituents
      identified, there is a major synergistic effect among the constituents. Since no
      single constituent tested was particularly potent, it remains to be determined
      whether these in-vitro cholinesterase inhibitory activities are relevant to in
      vivo effects of the ingestion of S. lavandulaefolia essential oil on brain
      acetylcholinesterase activity.

PMID- 10933143
TI  - Renal disease associated with hepatitis C infection after kidney and liver
      transplantation.

PMID- 10933144
TI  - A wake-up call for new strategies to improve living donor graft outcomes in
      pediatric kidney recipients.

PMID- 10933145
TI  - Making statistical sense of the transient immunodominance of HLA matching?

PMID- 10933146
TI  - On interleukin-8, neutrophil activation, and bronchiolitis obliterans syndrome in
      lung transplantation.

PMID- 10933147
TI  - Effect of hypothermic pulmonary artery flushing on capillary filtration
      coefficient.
AB  - BACKGROUND: We previously demonstrated that surfactant dilution and inhibition
      occur immediately after pulmonary artery flushing with hypothermic modified Euro
      Collins solution. Consequently, we speculated that increased capillary
      permeability contributed to these surfactant changes. To test this hypothesis, we
      evaluated the effects of hypothermic pulmonary artery flushing on the pulmonary
      capillary filtration coefficient (Kfc), and additionally performed a biochemical
      analysis of surfactant. METHODS: We used a murine isolated, perfused lung model
      to measure the pulmonary capillary filtration coefficient and hemodynamic
      parameters, to determine the wet to dry weight ratio, and to evaluate surfactant
      by biochemical analysis of lung lavage fluid. We defined three study groups. In
      group I (controls), we harvested lungs without hypothermic pulmonary artery
      flushing, and measured Kfc immediately. In group II (in situ flush), we harvested
      lungs after hypothermic pulmonary artery flushing with modified Euro-Collins
      solution, and then measured Kfc. Experiments in groups I and II were designed to
      evaluate persistent changes in Kfc after pulmonary artery flushing. In group III
      (ex vivo flush), we flushed lungs ex vivo to evaluate transient changes in Kfc
      during hypothermic pulmonary artery flushing. RESULTS: Groups I and II did not
      differ significantly in capillary filtration coefficient and hemodynamics. Group
      II showed significant alterations on biochemical surfactant analysis and a
      significant increase in wet-to-dry weight ratio, when compared with group I. In
      group III, we observed a significant transient increase in capillary filtration
      coefficient during pulmonary artery flushing. CONCLUSIONS: Hypothermic pulmonary
      artery flushing transiently increases the capillary filtration coefficient, leads
      to an increase in the wet to dry weight ratio, and induces biochemical surfactant
      changes. These findings could be explained by the effects of hypothermic modified
      Euro-Collins solution on pulmonary capillary permeability.

PMID- 10933148
TI  - Tumor necrosis factor-alpha neutralization reduces lung injury after experimental
      allogeneic bone marrow transplantation.
AB  - BACKGROUND: Idiopathic pneumonia syndrome (IPS) is a frequent and potentially
      fatal complication of bone marrow transplantation (BMT). We have previously shown
      that experimental IPS is associated with increased levels of lipopolysaccaride
      (LPS) and tumor necrosis factor-alpha (TNFalpha) in the bronchoalveolar lavage
      (BAL) fluid, and that administration of LPS to animals with extensive graft
      versus host exacerbated underlying lung injury (Blood 1996; 88: 3230). METHODS:
      Lethally irradiated CBA mice received BMT from allogeneic (B10.BR) or syngeneic
      (CBA) donors. The role of TNFalpha in the exacerbation of pulmonary toxicity
      caused by LPS injection and in the evolution of IPS after allogeneic BMT was
      examined by neutralizing TNFalpha after BMT using a soluble binding protein
      (rhTNFR:Fc). RESULTS: Five weeks after BMT, administration of rhTNFR:Fc
      dramatically reduced mortality and prevented the exacerbation of lung injury
      caused by LPS administration. This protective effect was associated with
      preservation of pulmonary function and with marked reductions of cells,
      neutrophils, and LPS in the BAL fluid of treated animals. TNFalpha neutralization
      from week 4 to 6 after allogeneic BMT effectively halted the progression of
      systemic GVHD and significantly reduced, but did not prevent lung injury that
      developed during the treatment period. CONCLUSIONS: We conclude that TNFalpha is
      central to early LPS induced toxicity in this model and is a significant, but not
      the exclusive contributor to the development of IPS after allogeneic BMT.

PMID- 10933149
TI  - Local blood flow regulation in transplanted rat pancreatic islets: influence of
      adenosine, angiotensin II, and nitric oxide inhibition.
AB  - BACKGROUND: Transplanted islets lack endothelial cells immediately after
      implantation and therefore depend on an adequate revascularization for their
      survival and function. However, the functional properties of the newly formed
      islet graft microvessels are largely unknown. This study aimed to investigate the
      blood flow regulation of transplanted pancreatic islets. METHODS: Pancreatic
      islets were syngeneically transplanted beneath the renal capsule of control and
      streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks
      later using laser-Doppler flowmetry. Adenosine (0.6 mg x kg(-1) x min(-1),
      angiotensin II (AT II; 0.17 microg x kg(-1) x min(-1)) and the nitric oxide
      synthase inhibitor NG-nitro-L-arginine (25 mg/ kg) were given to each animal.
      RESULTS: An increased basal blood flow and basal vascular conductance in the
      islet grafts, but not in the renal cortex, were seen in diabetic rats compared
      with control rats. Adenosine increased, and AT II decreased, the vascular
      conductance of the islet grafts in both nondiabetic and diabetic animals. A more
      pronounced circulatory response to AT II was observed in kidneys of diabetic
      animals, whereas there was no difference in the islet graft blood flow response
      between nondiabetic and diabetic animals. NG-Nitro-L-arginine decreased islet
      graft blood flow and vascular conductance in both nondiabetic and diabetic
      recipients, but the effect was more pronounced in the non-diabetic animals.
      CONCLUSIONS: Islet graft blood flow was influenced by adenosine, AT II, and
      nitric oxide inhibition in all animals. However, diabetic animals were less
      dependent on nitric oxide to maintain a basal blood flow in the islet graft.

PMID- 10933150
TI  - Predictors of graft survival in pediatric living-related kidney transplant
      recipients.
AB  - BACKGROUND: A successful kidney transplant from a living-related donor (LRD)
      remains the most effective renal replacement therapy for children with end-stage
      renal failure. The use of LRD kidneys results in decreased time on dialysis,
      increased graft survival, and better function compared with kidneys transplanted
      from cadaver donors. We retrospectively analyzed data from the United Network of
      Organ Sharing (UNOS) Scientific Renal Transplant Registry to determine risk
      factors for graft loss in children who received an LRD kidney. METHODS: Data was
      obtained from the UNOS Scientific Renal Transplant Registry on 2418 children
      ranging in age from 0 to 18 years who underwent an LRD kidney transplantation
      between January 1988 and December 1994. Multivariate analysis of graft survival
      was performed using Kaplan-Meier and Cox regression models. RESULTS: The effects
      of age, pretransplantation dialysis, early rejection, and race were found to
      significantly affect graft survival. Gender, peak panel-reactive antibody, and
      ABO blood type were not found to be significant risk factors. Infants <2 years of
      age initially had the worst graft survival; however, over time their results
      stabilized, and at 7 years estimated graft survival was good (71%). Adolescents
      ranging in age from 13-18 years had the best initial graft survival, but as time
      went on graft survival worsened (55%). Patients who underwent pretransplantation
      dialysis had a relative risk for graft loss of 1.77 (P<0.001), whereas those who
      had an early rejection had a relative risk for graft loss of 1.41 (P<0.002).
      African-Americans had a significantly higher relative risk for graft loss than
      either Caucasians (1.57, P<0.0005) or Hispanics (2.01, P<0.0003). CONCLUSIONS:
      Predictors of graft survival for children who receive LRD kidney transplants
      include age at transplantation, pretransplantation dialysis, early rejection, and
      race. Over time, adolescents and African-Americans seem to have the lowest graft
      survival.

PMID- 10933151
TI  - Comparative allograft histology after liver transplantation for cryptogenic
      cirrhosis, alcohol, hepatitis C, and cholestatic liver diseases.
AB  - BACKGROUND: End-stage liver disease for which no cause can be identified,
      cryptogenic cirrhosis, is a common indication for liver transplantation.
      Allograft inflammation and fibrosis have been reported to recur with similar
      frequencies after liver transplantation for cryptogenic cirrhosis and hepatitis C
      (HCV). METHODS: We determined sequential posttransplant allograft histology in
      four groups of recipients: 31 transplanted for cryptogenic cirrhosis, 70 for
      cholestatic etiologies, 40 for alcoholic liver disease, and 56 for HCV. Modified
      hepatitis activity index (HAI) and fibrosis stage were determined at 4 months, 1
      year, and at most recent biopsy posttransplantation. RESULTS: The prevalence of
      HAI > or = 2 among cryptogenic recipients was similar to that of cholestatic and
      alcoholic recipients at 4 months, 1 year, and at most recent evaluation (mean
      45+/-17 months posttransplantation). For HCV-infected recipients, the frequency
      of HAI > or = 2 was more than for cryptogenic recipients at 1 year (52 vs. 29%,
      P=0.04) and at most recent evaluation (64 vs. 15%, P=0.003). Fibrosis scores for
      cryptogenic, cholestatic, and alcoholic recipients were similar at all
      timepoints. The proportion of HCV-infected recipients with fibrosis stage >2 was
      more than that of cryptogenic recipients at 4 months (29 vs. 12%, P=0.05), 1
      years (46 vs. 7%, P=0.0002), and at most recent evaluation (42 vs. 15%, P=0.06).
      None of the cryptogenic recipients developed cirrhosis. RESULTS: The frequency of
      elevated HAI and fibrosis stage in recipients who undergo transplantation for
      cryptogenic cirrhosis is similar to that of recipients who undergo
      transplantation for cholestatic etiologies and significantly less than that of
      HCV-infected recipients. Fibrosis stage and HAI are generally stable after
      transplantation for cryptogenic cirrhosis. These data do not suggest a viral
      etiology of liver disease in the majority of patients with cryptogenic cirrhosis.

PMID- 10933152
TI  - Conversion from azathioprine [correction of azathioprina] to mycophenolate
      mofetil in pediatric renal transplant recipients with chronic rejection.
AB  - BACKGROUND: Chronic rejection is the leading cause of graft failure. Both
      nonimmunological and immunological mechanisms contribute to this pathology.
      METHODS: We studied changes in kidney function, mixed lymphocyte culture, cell
      mediated lympholysis, serum HLA class I antigens, cytotoxic antibodies, and
      lymphocyte population before and after 6 months of follow-up in 22 pediatric
      renal transplanted patients. The immunosuppressive protocol used was:
      cyclosporine, azathioprine, and corticosteroids. Eight patients demonstrated
      chronic graft rejection (by biopsy), group I; and eight patients had no clinical
      evidence of chronic and/or acute rejection, group II. Substitution of
      mycophenolate mofetil (MMF) (600 mg/m2 bid for azathioprine was done in patients
      of groups I and II. Another six patients with chronic rejection, did not receive
      MMF, group III. RESULTS: Creatinine clearance increased in group I (44+/-5 vs.
      51.1+/- ml/min/1.73 m2, P<0.03) but it decreased in group III (30+/-3 vs. 25+/-2,
      P<0.01). Urinary protein excretion decreased only in group I (0.3+/-0.03 to
      0.06+/-0.03 g/24 hr, P<0.03). During MMF therapy antidonor mixed lymphocyte
      culture decreased 62 and 70% (P<0.05) in group I and II. Cell-mediated
      lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group I.
      Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group
      II. Serum HLA class I antigens, only decreased from 0.7+/-0.1 to 0.5+/-0.1
      microl/ml, P<0.05, in group I. CD19+ decreased from 7.9+/-1.1 to 5.6+/-0.8%,
      P<0.05, and 7.8+/-1.2 to 5.5+/-0.9%, P<0.05, in groups I and II, respectively.
      CD16+ increased from 5.7+/-1.1 to 8.6+/-1.3 (P<0.05) only in group I.
      CONCLUSIONS: Our data suggest that substituting MMF for azathioprine therapy
      leads to an improvement in the immunosuppression and renal function in children
      with on-going chronic rejection.

PMID- 10933153
TI  - Bacteremia after intestinal transplantation in children correlates temporally
      with rejection or gastrointestinal lymphoproliferative disease.
AB  - BACKGROUND: Bacteremia occurs frequently after intestinal transplantation (ITx)
      in children. During our initial experience with this procedure, we noted that
      bacteremic episodes tended to occur simultaneously with the presence of rejection
      and/or gastrointestinal (GI) posttransplant lymphoproliferative disease (PTLD).
      AIM: To document the association of bacteremia with rejection and GI PTLD in
      pediatric ITx recipients. METHODS: Retrospective analysis of all medical records
      from 62 children who underwent ITx between July 1990 and January 1998 at
      Children's Hospital of Pittsburgh. A bacteremic episode was defined as two
      positive blood cultures from different sites at the same time or from the same
      site at different times. Rejection and PTLD were defined using previously
      published criteria. RESULTS: A total of 39/62 ITx recipients had 133 blood stream
      infections (2.1 episodes/patient) including 121 episodes of bacteremia and 12 of
      fungemia. Enteric organisms were the most frequently recovered pathogens (Gram
      negative rods, n=76; enterococci, n=36). Enteric organisms were recovered as a
      single organism (n=57), with another enteric bacteria (n=23), or with coagulase
      negative staphylococci (CONS) (n=24). CONS were recovered as a single organism on
      21 occasions. An obvious source of bacteremia was not found for 115/121 episodes.
      Endoscopy was performed for 107 of the 115 bacteremia episodes; an abnormal
      histology was identified in 74 revealing rejection (n=36), GI PTLD (n=21), or
      both (n=17). When endoscopy showed GI pathology, enteric organisms alone or in
      combination with CONS were recovered on 63/107 occasions, although CONS were
      recovered alone only 11 times. CONCLUSIONS: Bacteremia accompanies GI rejection
      and intestinal PTLD in ITx recipients. Endoscopy should be performed to inspect
      the allograft when bacteremia occurs without an obvious source in these patients.
      This is especially true for patients with bacteremia due to enteric organisms.

PMID- 10933154
TI  - Relationship of recipient age and development of chronic allograft failure.
AB  - BACKGROUND: The elderly are the fastest growing segment of the end stage renal
      disease (ERSD) population. Older renal transplant recipients experience fewer
      acute rejection episodes than do younger patients. Despite this, death censored
      graft survival is no better in these older transplant recipients than in younger
      recipients. We examined the United States Renal Data System (USRDS) database to
      determine whether recipient age itself has an independent effect on the
      development of chronic allograft failure (CAF). METHODS: We analyzed 59,509
      patients from the files of the USRDS. To determine whether age was an independent
      risk factor for CAF, the population was analyzed separately for Caucasians,
      African-Americans, and other ethnic groups. All renal transplant recipients from
      1988 to 1997 were examined. Both univariate and multivariate analysis were
      performed using chronic allograft failure as the outcome of interest. RESULTS:
      Actuarial 8-year censored graft survival was significantly decreased in the older
      age groups 67% for ages 18-49 vs. 61.8% for ages 50-64 vs. 50.7% for ages 65+
      (P<0.001). In the multivariate analysis, recipient age was a strong and
      independent risk factor for the development of chronic allograft failure in
      Caucasians (RR 1.29 for ages 50-64, RR 1.67 for ages older than 65). These
      findings were reinforced by an analysis that was restricted to living donor
      transplants without acute rejection. CONCLUSION: In Caucasians increased
      recipient age is an independent risk factor for the development of chronic renal
      allograft failure.

PMID- 10933155
TI  - Increased incidence of cardiac complications in kidney transplant recipients with
      cytomegalovirus disease.
AB  - BACKGROUND: The transplant literature has not shown cytomegalovirus (CMV) disease
      to be a significant risk factor for posttransplant cardiac complications. A large
      number of nontransplant studies have, however, reported an association between
      coronary heart disease (CHD) and CMV disease. Pathology studies have demonstrated
      a high incidence of CMV in atheromatous plaques from the coronary circulation.
      METHODS: We performed multivariate analysis to determine if posttransplant CMV
      disease was a significant risk factor for cardiac complications in kidney
      transplant recipients. We also performed univariate analysis to determine which
      cardiac complications were more common in the recipients with CMV disease.
      RESULTS: Between January 1, 1984 and June 30, 1997, 1859 adults underwent kidney
      transplants at our institution. Of these, 377 developed one of the following
      cardiac complications posttransplant: myocardial infarction, angina, arrhythmia,
      congestive heart failure, and angiographic vessel occlusion. By multivariate
      analysis, significant risk factors for one of the above cardiac complications
      were recipient age >50 years [odds ratio (OR)=2.5, P=0.0001], diabetes (OR=1.99,
      P=0.0001), a history of cardiac disease pretransplant (OR= 1.34, P=0.04), and CMV
      disease (OR=1.5, P=0.01). Univariate analysis demonstrated that recipients with
      CMV disease had a higher overall incidence of cardiac complications. Arrhythmias,
      congestive heart failure, and vessel occlusion were more common in those with CMV
      disease. The incidence of myocardial infarction, angina, and cardiac arrest did
      not differ between the two groups (recipients with versus without CMV disease).
      CONCLUSIONS: CMV disease is associated with an increased risk of cardiac
      complications in kidney transplant recipients. In our series, angiographic vessel
      occlusion was more common in recipients with CMV disease. This interesting
      finding may support the theory that CMV plays some role in the pathogenesis of
      CHD.

PMID- 10933156
TI  - Non-heart-beating donors from the streets: an increasing donor pool source.
AB  - BACKGROUND: Non-heart-beating donors have become a source for organ donation,
      especially kidneys. The emergency room and the critical care unit are the two
      sources for this kind of donor. Three years ago, our hospital began a policy of
      obtaining organs and tissues successfully from subjects who died in the streets.
      METHODS: We consider as potential organ donors people who die out-of-hospital,
      are less than 50 years old, with less than 15 min of asystolia without cardiac
      massage, with a known etiology of death, and without general contraindications
      for donating. After death diagnosis, the cadaver is taken to the hospital where
      an emergency room doctor certifies the death. Afterward, the cadaver is
      transferred to the operating room where a cardiopulmonary bypass is performed to
      preserve the organs while the legal aspects of donation go on. RESULTS: Up to
      now, 111 cadavers have been taken as non-heart-beating donors; 53 of them have
      been actual donors. The average time before arrival to the hospital was 68+/-2.64
      min, and the average interval between cardiac arrest and the beginning of
      cardiopulmonary bypass was 111.33+/-7.09 min. We have obtained 105 kidneys, 12
      livers, 84 corneas, and 31 pancreata for islets isolation as well as 49 long
      bones. Seventy-two kidneys were transplanted, with a probability of survival of
      83% at 36 months. CONCLUSIONS: Our experience indicates that it is possible to
      obtain organs for transplant from donors who die in the streets and are brought
      to the hospital under strict selection criteria.

PMID- 10933157
TI  - Permanent detrimental effect of nonimmunological factors on long-term renal graft
      survival: a parsimonious model of time-dependency.
AB  - PURPOSE: We attempted to model and test the pattern of effects of prognostic
      factors on renal graft survival during the posttransplantation time course.
      PATIENTS AND METHODS: Patients who received a cadaveric kidney-only transplant
      between January 1990 and December 1995 in Eurotransplant, who received
      cyclosporine as induction therapy, and who had a complete follow-up at the time
      of analysis were included in the study (n= 10614). An index summarizing all
      covariate information was calculated and used for modeling the time-dependent
      effects with relation to graft failure. RESULTS: The immunological factors (HLA
      mismatch and % panel-reactive antibody) were seen to have a slowly decreasing
      negative effect on renal graft survival. The cold ischemic trauma (>24 hr)
      exerted a permanent detrimental effect on the grafts. The use of organs obtained
      from old donors was associated with a constant higher risk of graft loss.
      CONCLUSIONS: An analysis of determinants of human allograft dysfunction should
      also study the interaction between the effects and time. Nonimmunological factors
      had a constant detrimental effect on graft failure, whereas the impact of the
      immunological factors--although remaining important for late graft loss--very
      slowly decreased. In the context of marginal transplants, clustering of
      unfavorable factors should be avoided to prevent late graft losses.

PMID- 10933158
TI  - Epitope analysis of HLA class I donor specific antibodies in sensitized renal
      transplant recipients.
AB  - OBJECTIVE: The goal of this study was to evaluate the epitope specificity of
      donor-specific HLA class I antibodies detected in the serum of alloimmunized from
      a previous renal graft patients. METHOD: A total of 410 serum samples from 87
      patients who had lost a previous graft, were collected every 4 months during a 2
      year follow-up period. All recipients and donors were typed for class I HLA
      antigens by a standard lymphocytotoxicity technique. To define the specificities
      of the HLA class I antibodies, two techniques were used in parallel: the
      antihuman globulin augmented CDC (AHG-CDC) technique and an ELISA technique. The
      mismatched HLA-antigens and the detected HLA class I antibodies were categorized
      as intra-cross-reactive group mismatches (intra-CREGs-MMs) and other-CREG-MMs.
      For each sensitized patient actual and at risk epitope specificities were
      defined. RESULTS: Thirty-eight patients (43.7%) had developed IgG HLA class I
      specific antibodies with stable specificities against mismatched alloantigens
      from the previous graft. A total of 60 antibody reactivity patterns and 82
      specificities against private and public epitope were recognized. Patients with
      only intra-CREGs-MMs produced HLA class I-specific antibodies less frequently
      than patients with only other-CREG-MMs, although the difference was nearly
      statistically significant (P=0.053). All HLA class I donor-specific antibodies
      were considered to have specificities against the private epitopes of the
      mismatched graft HLA-antigens. In the cases where HLA class I alloreactivity was
      spreading to more than one donor antigens, we considered that the detected
      antibodies had specificities against the private and the shared between the
      alloantigens epitope(s). No epitope-specific antibodies were detected against
      shared epitopes between the mismatched alloantigens and the HLA-antigens of the
      patients. In 11/38 cases (28.9%) HLA class I alloreactivity spreading to non
      graft antigens was detected. These antibodies were directed against HLA-antigens
      that share epitope(s) and have strong serological reactivity with the immunogenic
      alloantigens. CONCLUSION: Our data show that a small number of private and public
      alloepitopes seem to be responsible for antibody production in patients
      sensitized from a previous graft. A detailed description of these HLA-epitopes,
      in the context of clinical graft complications, may lead to an improved organ
      allocation strategy.

PMID- 10933159
TI  - Immunophilins may limit calcineurin inhibition by cyclosporine and tacrolimus at
      high drug concentrations.
AB  - BACKGROUND: The immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK506
      or FK) are qualitatively similar but differ in molar potency. Both drugs
      sterically inhibit the phosphatase activity of calcineurin (CN) but differ in
      molar potency. In our study we explored whether differential inhibition of CN
      explained the differences in molar potency of FK versus CsA. METHODS: We compared
      their effects on NFATC2 dephosphorylation using Western analysis, interferon
      gamma production using ELISA, and CN phosphatase activity using the CN assay in
      human peripheral blood leukocytes (PBL) and mouse spleen cell suspension.
      RESULTS: The FK concentration inhibiting 50% (IC50) of all three activities was
      approximately 0.2 microg/ml in human PBL, versus 5-20 microg/ml for CsA. Although
      inhibition of interferon-gamma secretion and NFATC2 dephosphorylation was
      complete, inhibition of CN phosphatase activity was incomplete with both drugs at
      saturation, particularly with FK. Inhibition of CN phosphatase activity was
      incomplete whether FK treatment was in vivo in mouse or in vitro in various human
      and mouse tissues, especially brain. Exogenous FKBP12 or CyPA increased CN
      phosphatase inhibition, suggesting that incomplete inhibition of CN phosphatase
      activity reflected limiting amounts of active immunophilin. CONCLUSIONS: These
      data contradict the prevailing assumption that immunophilins are abundant and not
      limiting for inhibition of CN by CsA or FK. Further, the observation that FK and
      CsA completely inhibit immune function without completely inhibiting CN suggests
      that the inhibition of immune function is not mediated by general CN inhibition
      but by inhibition of a subset of CN which is critical for lymphocyte activation.

PMID- 10933160
TI  - Prolongation of liver allograft survival after interleukin-10 gene transduction
      24-48 hours before donation.
AB  - BACKGROUND: Interleukin- (IL) 10 may be a potent regulator for controlling of
      allograft rejection. A single administration of IL-10 is not effective for
      controlling graft rejection. Gene transfer is an attractive vehicle for
      prolonging the expression of short-lived proteins. METHODS: Donor or recipient
      livers were transduced with 1 x 10(10) p.f.u. of replication-deficient adenovirus
      vectors harboring human IL-10 cDNA (AdCMVhIL-10) via the ileocecal vein before or
      after rat orthotopic liver transplantation. RESULTS: DA allografts given AdCMVhIL
      10 24-48 hr before donation survived for more than 56 days in Lewis recipients,
      although DA allografts given the adenovirus vector 7 days or 6 hr before, and 3
      days after transplantation were rejected within 30 days in recipients. Serum
      levels of human IL-10 in gene-transferred rats were maximum from day 2 to 7. The
      serum level of human IL-10 then decreased gradually, and human IL-10 was not
      detected by ELISA 30 days after gene-transduction. In gene-transduced long-term
      surviving liver allografts, IL-10 was expressed, and the expression of IL-4 was
      also up-regulated on posttransplant day 3, despite the expression of Th1
      cytokines (IL-2 and interferon-gamma), although in rejected liver allografts, IL
      2 and interferon-gamma were expressed without expression of IL-4 and IL-10.
      CONCLUSIONS: The prolongation of survival of IL-10 cDNA transferred liver
      allografts might be due to inhibition of the early phase of alloimmune-response
      by over expression of IL-10, despite the expression of IL-2 and interferon-gamma.

PMID- 10933161
TI  - Increased protein synthesis after T cell activation in presence of cyclosporin A.
AB  - BACKGROUND: The immunosuppressive drug, cyclosporin A (CsA), blocks immune
      responses by inhibiting the calcineurin-dependent dephosphorylation of the
      nuclear factor of activated T cells (NFAT). We have previously reported that T
      cells activated in presence of CsA exhibit particular properties. In our study,
      we have tested the hypothesis that T cells activated in presence of CsA display a
      differential pattern of gene expression. METHODS: T lymphocytes were activated in
      vitro by Concanavalin A with or without CsA. The cells were: (1) pulsed with 35S
      methionine to label the newly synthesized proteins that in turn were revealed by
      2D-gel electrophoresis; (2) analyzed by flow cytometry for activation markers
      expression; and (3) examined by gel electrophoresis for early tyrosine
      phosphorylation events. RESULTS: The proteomic patterns of T lymphocytes
      activated by Concanavalin A, with or without CsA, were compared. In keeping with
      the well-known effect of the immunosuppressor, many polypeptides were not found
      in its presence. Remarkably, several newly synthesized polypeptides were detected
      only when activation was carried out in presence of CsA. In addition,
      immunologically relevant proteins, such as CD44 and CD69, escape CsA-inhibitory
      action. Furthermore, CsA did not modify the early protein tyrosine
      phosphorylation events resulting from T cell triggering. CONCLUSIONS: The present
      data show that the effect of CsA on protein synthesis is more complex than
      anticipated. Signaling provided by T cell activation and the blockade of the
      calcineurin-dependent pathway by CsA results in an altered program of gene
      expression.

PMID- 10933162
TI  - Graft-versus-leukemia effect in minor antigen mismatched chimeras given delayed
      donor leucocyte infusion: immunoregulatory aspects and role of donor T and ASGM1
      positive cells.
AB  - BACKGROUND: Previous studies have demonstrated that delayed donor leukocyte
      infusion (DLI) can increase graft-versus-leukemia (GVL) without increasing graft
      versus-host-disease (GVHD) in MHC mismatched bone marrow (BM) chimeras. In our
      report, the immune status of minor antigen mismatched BM chimeras given DLI was
      studied. Particularly the role of donor ASGM1 positive or T cells in the graft
      versus-leukemia effect (GVL) was investigated. METHODS: AKR mice (H2k, Mls1a,
      Thy1.1) received TBI (9,5 Gy) and T cell-depleted (TCD) C3H (H2k, Mls2a, Thy1.2)
      BM alone (BM chimeras), or TCD BM together with immunocompetent C3H spleen cells
      at the time of BM transplantation (BM+SP chimeras), or TCD BM and 3 weeks later
      C3H spleen cells (DLI chimeras). Chimerism and T lymphocyte subsets were scored
      using FACS and anti-Thy, anti-Vbeta6, anti-IL2-beta receptor, anti-CD4, anti-CD3,
      and anti-CD8 mAbs. Leukemia challenge consisted of 5 x 10(6) AKR T cell lymphoma
      (BW4157) cells injected i.v. ASGM1 positive (ASGM1+) cells and T cells were
      depleted using anti-ASGM1 or anti-Thy1.2 antibodies, respectively. Immune
      tolerance was studied using MLR and CML tests. RESULTS: BM + SP chimeras
      developed acute and lethal GVHD, whereas DLI chimeras were totally free from
      GVHD. In DLI chimeras, host-reactive cytotoxic T cells (CTL) could not be induced
      and host-reactive CD8Vbeta6 cells were deleted whereas CD4Vbeta6 cells and MLR
      reactivity persisted temporarily. In contrast, in BM+SP chimeras, anti-host CTL
      were easily generated and an expansion of both host-reactive CD8Vbeta6 and
      CD4Vbeta6 T cells was found as well as high anti-host MLR reactivity. Depletion
      of either ASGM1 + cells or T cells from the DLI inoculum resulted in an
      abrogation of GVL reactivity, suggesting that both cell populations were involved
      in the protection against BW4157 leukemia. Three weeks after DLI, the GVL effect
      waned which correlated with the disappearance of host-reactive CD4 cells and MLR
      reactivity. CONCLUSION: In minor antigen mismatched BM chimeras, anti-host
      reactivity after DLI is characterized by (1) an absence of clinical GVHD, (2)
      clonal deletion of host-reactive CD8 cells, (3) an absence of anti-host CTL
      induction, and ( 4) a temporary persistence of host-reactive CD4 T cells and of
      MLR reactivity. In addition, either donor ASGM1+ cells or an interaction between
      these cells and T cells contribute to the GVL effect.

PMID- 10933163
TI  - Cyclosporine inhibits class II major histocompatibility antigen presentation by
      xenogeneic endothelial cells to human T lymphocytes by altering expression of the
      class II transcriptional activator gene.
AB  - BACKGROUND: Cyclosporine (CsA) is currently given to recipients of vascularized
      xenografts as part of the immunosuppressive regimen required to prevent the
      hyperacute rejection phase. The effects of CsA on non-lymphoid immune cells, such
      as endothelial cells (ECs), have not been well characterized and sometimes seem
      contradictory, because both protective and adverse effects have been reported. In
      the present study, we investigated in vitro whether CsA could alter the
      antigenicity of activated porcine aortic endothelial cells (PAECs) by reducing
      class I and class II MHC antigen expression. METHODS: The effect of CsA on MHC
      antigen expression during tumor necrosis factor (TNF)-alpha- or lymphocyte
      mediated PAEC activation was evaluated in vitro by flow cytometry and correlated
      to the ability of porcine ECs to promote human T lymphocyte proliferation. The
      effect of CsA on class II MHC antigen mRNA expression was also analyzed and
      related to class II transcriptional activator (CIITA) mRNA expression. RESULTS:
      Flow cytometry analysis showed that TNF-alpha-mediated induction of class II MHC
      antigen expression on PAECs was completely inhibited by CsA, whereas expression
      of class I MHC was reduced by 50%. The inhibition was dose dependent (at drug
      concentrations ranging from 2.5 microg/ml to 20.0 microg/ml) and was consistently
      observed at all time points (24-72 hr) during the activation period. Decreased
      MHC antigen expression dramatically reduced the ability of PAECs to further
      promote human T-cell proliferation. Similar levels of inhibition were achieved
      using an anti-porcine class II MHC blocking monoclonal antibody. Pretreatment of
      PAECs with CsA for 4 hr before coculture with human peripheral blood leukocytes
      efficiently blocked the induction on PAECs of E-selectin and class II MHC
      antigens and inhibited overexpression of class I antigens. Semiquantitative
      reverse transcriptase-polymerase chain reaction experiments showed that CsA
      markedly reduced the steady-state level of porcine class II (SLA-DRA and SLA-DQA)
      mRNA at 16 hr, compared with PAECs stimulated with TNF-alpha alone. The reduced
      level of class II MHC mRNA was associated with a lack of CIITA expression at this
      time point, suggesting that CsA could alter transcription or promote the rapid
      decay of CIITA mRNA. CONCLUSION: Our study indicates that CsA could play a role
      in preventing porcine MHC antigens being directly presented to human T
      lymphocytes by xenogeneic ECs.

PMID- 10933164
TI  - Elevated levels of interleukin-8 and transforming growth factor-beta in
      bronchoalveolar lavage fluid from patients with bronchiolitis obliterans
      syndrome: proinflammatory role of bronchial epithelial cells. Munich Lung
      Transplant Group.
AB  - BACKGROUND: Obliterative bronchiolitis (OB), the most important long-term
      complication after lung transplantation, is thought to be a manifestation of
      chronic rejection within the airways, with the hallmarks inflammation and
      fibroproliferation. METHODS: To characterize the inflammatory process in the
      context of OB we quantified tumor necrosis factor-alpha, interleukin (IL)-8, IL
      10, and transforming growth factor (TGF)-beta on the protein and mRNA level in
      bronchoalveolar lavage fluid samples obtained from patients with bronchiolitis
      obliterans syndrome (BOS) and without BOS. In addition, bronchial cells sampled
      by bronchial brushing were analyzed for mRNA expression. RESULTS: In respiratory
      epithelial lining fluid (ELF) from BOS patients the protein levels of IL-8
      (52.4+/-22.2 vs. 4.4+/-0.9 pg/ml ELF, P<0.005) and TGF-beta (5.6+/-1.9 vs. 0.9+/
      0.2 ng/ml ELF, P<0.005) were significantly elevated. In addition, bronchoalveolar
      lavage fluid cells of BOS patients showed increased expression of TGF-beta
      (1.13+/-0.44 vs. 0.45+/-0.16, optical density [O.D.]/O.D. glyceraldehyde-3
      phosphate dehydrogenase [GAPDH], P=0.11) and IL-8 (0.25+/-0.13 vs. 0.09+/-0.03
      O.D/O.D. GAPDH, P=0.53) without the differences reaching statistical
      significance. In contrast, IL-8 mRNA expression of bronchial cells was
      significantly higher in the BOS group (0.85+/-0.40 vs. 0.22+/-0.10 O.D./O.D.
      GAPDH, P<0.05). CONCLUSIONS: We assume that IL-8 and TGF-beta may act as key
      mediators for airway inflammation and fibroproliferation in the pathogenesis of
      OB, with bronchial epithelial cells serving as a relevant source of IL-8.

PMID- 10933166
TI  - African-American renal transplant recipients experience decreased risk of death
      due to infection: possible implications for immunosuppressive strategies.
AB  - INTRODUCTION: African-American renal transplant recipients tend to experience
      more acute rejection episodes and have shorter graft survival than Caucasian
      renal transplant recipients. Various factors have been posited to be responsible
      for this difference, including relative under immunosuppression. We reasoned that
      by looking at the balance of acute rejections versus death due to infection, we
      could ascertain whether African-American renal recipients might have more reserve
      to tolerate an increase in pharmacological immunosuppression. METHODS: We
      analyzed the United States Renal Data System (USRDS) data from 1987 to 1997
      regarding acute rejection episodes and infectious deaths. All other pertinent
      factors were gathered for a multivariate analysis. A total number of 68,885 adult
      renal transplant recipients were analyzed. RESULTS: When corrected for all
      covariates, the relative risk for acute rejection (1.3) was higher although the
      relative risk for infectious death was lower (0.7) in African-Americans as
      compared with Caucasians (P<0.01). CONCLUSION: Our study would indicate that
      relative to Caucasians, African-American renal transplant recipients are at
      decreased risk for infectious death and therefore may tolerate the more intensive
      immunosuppression that may be necessary to narrow the gap in acute rejection
      rates between African-Americans and Caucasian renal transplant recipients.

PMID- 10933165
TI  - Association of natural killer cell depletion with induction of mixed chimerism
      and allograft tolerance in non-human primates.
AB  - BACKGROUND: Nonmyeloablative T cell depletion followed by donor bone marrow
      infusion has proved to be an effective approach to induction of mixed chimerism
      and tolerance of organ allografts in non-human primates. To help define the
      mechanisms involved we have compared T cell depletion with ATG versus anti-CD2
      monoclonal antibody with respect to establishment of mixed chimerism and
      induction of tolerance. METHOD: Both nonmyeloablative regimens included low dose
      total body irradiation (1.5 Gy x 2), thymic irradiation (7 Gy), splenectomy and
      kidney plus donor bone marrow transplantation, followed by a 4-week
      posttransplant course of cyclosporine. In addition, the ATG group (13 recipients)
      received antithymocyte globulin, although the LOCD2b group (10 recipients) were
      treated with an anti-CD2 monoclonal antibody (LOCD2b). RESULTS: In the ATG group,
      11 of 13 monkeys developed multilineage chimerism and 9 survived for more than
      100 days without kidney allograft rejection. In contrast, 0/10 monkeys in the
      LOCD2b group developed chimerism, 5 died of infection and 5 suffered progressive
      rejection; only 1 recipient survived beyond 100 days. Sequential monitoring of
      peripheral blood mononuclear cells revealed greater T cell (CD3+) depletion in
      the LOCD2b-treated animals compared to those receiving ATG. However, NK cells
      (CD16+CD8+) were significantly more depleted in the ATG group and NK function
      remained abrogated longer after ATG than LOCD2b treatment (3 weeks vs. <5 days).
      CONCLUSION: Despite excellent T cell depletion by LoCD2b, ATG was more effective
      in inducing chimerism and tolerance. This difference correlated with anti-NK
      activity of the two reagents. These data suggest that NK cells may also resist
      engraftment of allogeneic bone marrow cells in this model.

PMID- 10933168
TI  - Inducible nitric oxide synthase transcription in human lung transplantation.
AB  - BACKGROUND: Recent animal data suggest that inducible nitric oxide synthase
      (iNOS) mRNA expression in the bronchoalveolar lavage (BAL) may be useful for the
      diagnosis of lung rejection. The aim of this study was to evaluate iNOS mRNA
      transcription in the BAL fluid of human lung allografts. METHODS: iNOS mRNA
      transcription was quantified by competitive reverse transcription-polymerase
      chain reaction in 51 BAL cell pellets of lung transplant patients. According to
      bacteriological and histological results, BAL samples were divided into three
      groups: normal (n=21), acute rejection (AR, n=15), and infection (INF, n=15).
      RESULTS: Compared with the control group, iNOS transcription increased
      significantly with INF (P=0.0005) but only slightly with AR (P>0.05). INF values
      were significantly higher than AR values (P=0.0029). CONCLUSION: BAL iNOS mRNA
      transcript determination by competitive reverse transcription-polymerase chain
      reaction may be useful in differentiating infected from normal and/or acutely
      rejecting allografts.

PMID- 10933167
TI  - Cytokine-induced functional suppression of microencapsulated rat pancreatic
      islets in vitro.
AB  - BACKGROUND: It is likely that inflammatory cytokines are released near
      microencapsulated islets in vivo. METHODS: Rates of insulin release or glucose
      oxidation were measured after culture of microencapsulated rat islets with
      interleukin (IL)-1beta and tumor necrosis factor-(TNF-alpha). Their ability to
      recover from IL-1beta-induced suppression was also investigated. RESULTS:
      Microencapsulated islets were suppressed after exposure to IL-1beta, which was
      potentiated by TNF-alpha. After exposure to lower IL-1beta concentrations,
      microencapsulated islets had similar oxidation rates as corresponding controls.
      At higher concentrations, microencapsulated islets were more suppressed than
      nonencapsulated islets. Microencapsulated and control islets were able to recover
      from suppression after exposure to 2.5 U/ml of IL-1beta. CONCLUSIONS:
      Microencapsulation using the present alginate/poly-L-lysine/alginate capsules
      does not protect islets against the detrimental effects of IL-1beta and TNF
      alpha. Indeed, microencapsulated islets seem to be more susceptible to
      suppression at higher concentrations of IL-1beta. However, after exposure to a
      lower concentration of IL-1beta, microencapsulated islets can recover.

PMID- 10933169
TI  - Serum erythropoietin levels in kidney donors after renal transplantation.
AB  - BACKGROUND: Renal transplantation is the treatment of choice for many patients
      with end-stage renal disease. In the donor, renal excretory function is not
      affected after nephrectomy; however, little is known about other functions such
      as erythropoietin production. We studied the erythropoietin production in renal
      donors after nephrectomy. METHODS: We included healthy individuals fulfilling the
      criteria for kidney donation. Blood samples were collected before and monthly
      from 1 to 6 months after nephrectomy. Complete blood cell counts and
      erythropoietin were assayed. RESULTS: Eight kidney donors were studied. A
      significant increase in erythropoietin levels was observed during the first 3
      months, but no difference was observed by the 4th month as compared with basal
      values. CONCLUSIONS: Erythropoietin production rose during the first 3 months
      after nephrectomy. However, erythropoietin was normal by the 4th month. Unchanged
      hemoglobin levels may suggest that the compensatory production of erythropoietin
      could participate in the preservation of an adequate physiological status of the
      donor after nephrectomy.

PMID- 10933170
TI  - Initial results of solitary pancreas transplants performed without regard to
      donor/recipient HLA mismatching.
AB  - BACKGROUND: We hypothesized that solitary pancreas transplants could be performed
      successfully even in the presence of poor HLA matching if an aggressive approach
      were taken with regard to immunosuppressive protocol and the performance of
      allograft biopsy. METHODS: Seven pancreas-after-kidney transplants and seven
      pancreas transplants alone were performed without consideration given to the
      degree of HLA mismatching (MM) using tacrolimus (FK506)/mycophenolate mofetil
      (MMF)/prednisone maintenance therapy. Mean (+/-SD) total HLA MM was 4.8+/-1.2.
      All patients were followed for at least 6 months. The first four cases were
      induced with ATGAM for 7 to 10 days. In the remaining 10 cases, an ultrasound
      guided percutaneous needle biopsy was attempted on a protocol basis 10 days after
      completing induction with OKT3 for 7 (n=2) or 14 (n=8) days. RESULTS: Overall
      patient survival, graft survival, and incidence of acute rejection requiring
      treatment were 86, 79, and 50%, respectively. Two patients receiving ATGAM
      developed grade III-IV rejection at 3 weeks. Both patients receiving OKT3 for 7
      days developed early grade III rejection. However, only three of eight patients
      receiving OKT3 for 14 days developed rejection requiring treatment. Protocol
      biopsy was successfully performed in six of seven patients and uncovered three
      cases of otherwise undetectable grade III-IV rejection. CONCLUSIONS: Although
      based on a small number of cases, our results suggest that solitary pancreas
      transplants with a poor HLA match can be performed with an acceptable rejection
      incidence and graft survival rate using an OKT3/FK506/MMF/prednisone regimen with
      protocol biopsy.

PMID- 10933171
TI  - Detection and monitoring of intracranial pressure dysregulation in liver failure
      by ultrasound.
AB  - BACKGROUND: Development of elevated intracranial pressure (ICP) in hepatic
      failure indicates poor prognosis. Its detection by invasive methods poses
      methodological problems. We applied ultrasound studies of the optic nerves to
      noninvasively estimated ICP status. METHODS: A total of 22 pediatric patients
      with hepatic failure were examined by serial B scan ultrasound and followed up
      clinically. Outcome was scored as survival or death due to multiorgan failure
      (MOF) or raised ICP. In 18 patients, transplantations were performed. RESULTS:
      Four patients died before transplantation was possible (raised ICP: n=3, MOF:
      n=1). After OLT there were 10 survivors and 8 patients died (MOF: n=3, raised
      ICP: n=5). In 10 patients we found optic nerve sheath diameter (ONSD) above
      normal limits. Eight patients died, mostly because of raised ICP (n=7). Only 2 of
      the 10 survivors experienced a transient ONSD increase, steadily normalized after
      transplantation. Preoperatively, normal ONSD was detected in four of seven
      patients. The outcome of these four cases was clearly superior (three survivors
      and one MOF) compared with abnormal pre-OLT ultrasound findings (raised ICP:
      n=3). CONCLUSION: Patients with poor prognosis related to raised ICP in pediatric
      liver failure can be identified by ultrasound measurement of ONSD without the
      disadvantages of invasive procedures. Although the exact intracranial pressure
      level cannot be deduced from single examinations, ONSD trends can reflect the
      evolution of ICP in hepatic encephalopathy.

PMID- 10933172
TI  - Persistent human herpesvirus 8 viremia before Kaposi's sarcoma development in a
      liver transplant recipient.
AB  - HHV8 DNA has been detected in essentially all Kaposi's sarcoma (KS) lesions
      investigated, including those associated with transplantation. However, the
      possibility of human herpesvirus 8 (HHV8) detection in serum before appearing in
      the tumor is unknown. We therefore studied the natural history of HHV8 infection
      in a liver transplant recipient who developed KS 9 months after receiving the
      hepatic allograft. The presence of HHV8 DNA was retrospectively analyzed by using
      polymerase chain reaction in frozen stored follow-up serum specimens and KS
      tissues (skin and lymph node biopsies). Although KS was diagnosed the day +279
      posttransplant by histopathological examination of KS tissues, retrospective
      analysis showed that HHV8 DNA was present in all successive serum specimens taken
      from the day +119 onward. Accordingly, asymptomatic and persistent HHV8 viremia
      may precede the appearance of typical KS lesions. Monitoring transplant
      recipients for HHV8 could be useful for developing therapeutic and prophylactic
      strategies.

PMID- 10933173
TI  - Prevention of cardiac allograft arteriosclerosis using antisense proliferating
      cell nuclear antigen oligonucleotide.
AB  - Cardiac allograft arteriosclerosis limits long-term survival of recipients and is
      characterized by intimal thickening comprised of proliferative smooth muscle
      cells. Proliferating-cell nuclear antigen (PCNA) plays a pivotal role in the cell
      cycle regulatory genes involved in smooth muscle cell proliferation. To test the
      hypothesis that antisense PCNA oligodeoxynucleotide (ODN) can prevent allograft
      arterial intimal hyperplasia, we performed single intraluminal delivery of the
      antisense or sense PCNA ODN or no transfer into murine cardiac allografts. DBA/2
      murine hearts were transfected and transplanted into B10.D2 mice; the allografts
      were harvested 4 weeks later. Severe intimal thickening with enhanced expression
      of PCNA was observed in untransfected and sense PCNA ODN-treated allografts,
      whereas antisense PCNA ODN prevented neointimal formation.

PMID- 10933174
TI  - Questionable long-term benefit of mycophenolate.

PMID- 10933175
TI  - Risk factors for tumor development after renal transplantation.

PMID- 10933176
TI  - CD34 selected alloPBSCT and adoptive immunotherapy.
AB  - To circumvent aGVHD in the early phase after allogeneic stem cell transplantation
      but to provide GVL activity later on, we performed alloPBSCT with CD34+ selected
      grafts followed by delayed add-back of CD3+ T cells. Ten consecutive patients
      having an HLA-identical sibling donor were enrolled on to this trial. Four
      patients were in first CR of high-risk ALL, another four in first CR of AML, one
      was in second myeloid blast crisis of CML, and one was in PR of relapsed NHL.
      Conditioning consisted of 2 x 60 mg/kg CY plus 12 Gy TBI. G-CSF (Filgrastim)
      mobilized peripheral cells were CD34+ selected using the Isolex 300i system in
      nine patients and the CliniMacs system in one. Median CD34+ purity was 86%. A
      median of 2.8 x 10(6)/kg CD34+ cells were transplanted. The number of CD3+ cells
      in the allografts was 5.7 x 10(4)/kg (median) after Isolex 300i, and 0.2 x
      10(4)/kg after CliniMacs. All patients received G-CSF (Filgrastim) and engrafted
      rapidly. Standard-dose CsA was administered, and until day +60 no aGVHD occurred.
      At that time point, seven patients received 2 x 10(6)/kg CD3+ cells while CsA had
      been tapered to 50% of the starting dose. One of these patients died after a
      second T cell boost given on day +90 without concomitant immunosuppression due to
      grade IV intestinal aGVHD. Three others developed cutaneous cGVHD. Taken
      together, T cell depletion by CD34+ selection does not impair rapid engraftment
      in the HLA-identical sibling donor setting. Using standard-dose CsA the risk for
      acute GVHD seems to be minimized. Add-back of 2 x 10(6)/kg CD3+ cells on day +60
      with CsA protection is feasible. However, whether this is the optimal time point
      and number of T cells remain to be further elucidated.

PMID- 10933177
TI  - Faster engraftment of neutrophils and platelets with peripheral blood stem cells
      from unrelated donors: a comparison with marrow transplantation.
AB  - Engraftment was achieved in 43/45 (95%) recipients of peripheral blood stem cells
      (PBSC) from HLA-compatible unrelated donors (n = 45), compared to all 45 patients
      in matched controls receiving bone marrow and 14/18 (78%) recipients of CD34
      selected PBSC (P < 0.01). The time to reach ANC >0.5 x 10(9)/l was a median of 16
      days in the PBSC and CD34 groups, compared to 20 days in the bone marrow controls
      (P < 0.001 vs PBSC). The time to reach platelets >50 x 10(9)/l was a median of 23
      days in the PBSC group and 24 days in the CD34 group, which was significantly
      faster than 29 days in the bone marrow controls (P < 0.01). Acute GVHD grades II
      IV developed in 30% in the PBSC group, 20% in the recipients of bone marrow and
      18% in the CD34 group. The corresponding figures for chronic GVHD were 59%, 85%
      and 0% (P < 0.01) in the three groups, respectively. The probability of non
      relapse death was 27% in the recipients of PBSC, 21% in the bone marrow controls
      and 60% in the CD34 group (NS). The 2-year leukaemia-free survival was 46% in the
      PBSC group, 41% in the bone marrow group and 25% in the CD34 group (NS).

PMID- 10933178
TI  - CD34+ selected cells in mismatched stem cell transplantation: a single centre
      experience of haploidentical peripheral blood stem cell transplantation.
AB  - Over the past 3 years we have performed 10 haploidentical peripheral blood stem
      cell transplants in patients with incurable haematological malignancies and no
      prospect of a matched unrelated donor within an adequate time period.
      Conditioning consisted of ATG, TBI, thiotepa, cyclophosphamide and additional
      radioimmunotherapy in five patients. All patients received G-CSF mobilized
      peripheral blood stem cell grafts. GVHD prophylaxis consisted of T cell depletion
      by CD34+ selection; no post-transplant immunosuppression was given in nine
      patients. Stable engraftment was achieved in nine patients; one case of acute
      graft rejection was observed. Seven patients developed grade I acute GVHD, and
      six patients have developed chronic GVHD. Infections were the most significant
      clinical problem post transplant. Two patients have suffered a relapse of their
      disease and two further patients have died of transplant-related complications.
      After a median follow-up of 13 months (range 5-37 months) six patients are
      surviving in remission. We conclude that haploidentical PBSCT is a reasonable
      alternative to a MUD transplant.

PMID- 10933179
TI  - New strategies in the treatment of graft-versus-host disease.
AB  - GVHD continues to be a major complication after allogeneic hematopoietic stem
      cell transplantation even when the recipient is given immunosuppression for the
      prophylaxis of this severe disease. There have been many advances in the
      prevention and treatment of GVHD, using compounds such as cyclosporine, FK506,
      mycophenolate mofetil or monoclonal IL-2 receptor antagonist. New strategies seem
      to include sequential therapy involving the blocking of both endogenous cytokines
      and alloreactive donor cells. However, further clinical and laboratory studies
      are needed in order to improve the therapy of established GVHD.

PMID- 10933180
TI  - New strategies in GVHD prophylaxis.
AB  - Despite immunosuppressive therapy using cyclosporine (CsA) and prednisolone and
      methotrexate (MTX), the incidence for aGVHD grade II to IV after transplantation
      from HLA matched unrelated donors (MUD) is 78%, the incidence for grade III and
      IV 36%. Since GVHD contributes to morbidity and mortality after MUD-BMT, a more
      effective prophylactic regimen is needed in order to prevent these transplant
      associated complications. Recently, we described that mycophenolate mofetil (MMF,
      CellCept), an immunosuppressive agent successfully used for the prevention of
      acute rejection in renal allograft recipients, can safely and effectively be used
      for the treatment of aGVHD in hematopoietic stem cell transplantation.
      Information on the i.v. formulation of mycophenolic acid (MPA) is not yet
      available. Here we report on the i.v. formulation of MMF in hematopoietic stem
      cell recipients. MMF is effective in the prophylaxis of acute GVHD after stem
      cell transplantation; the optimal dosage needs further investigation. At the
      present time the relevance of measurement of plasma MPA concentrations on MMF
      dosage is not yet understood and further evaluation is required.

PMID- 10933181
TI  - New strategies in allogeneic stem cell transplantation: immunotherapy using
      irradiated allogeneic T cells.
AB  - Recipients of T cell-depleted allogeneic bone marrow transplants have increased
      risks of relapse and graft rejection. The addition of donor T cells to the TCD
      allograft will decrease the risk of graft rejection but will increase the risk of
      graft-versus-host disease (GVHD). Relapse of leukemia or lymphoma following
      allogeneic bone marrow transplantation can be successfully treated with post
      transplant infusions of donor lymphocytes. A relatively small number of donor T
      cells can have a profound anti-tumor effect and facilitate engraftment, but has
      an unpredictable potential for severe GVHD. An alternative to using viable
      immunocompetent donor immune cells to facilitate engraftment and to treat
      relapsed patients are donor lymphocytes that have been treated to limit their
      ability to proliferate and cause GVHD. T cells treated with irradiation retain
      cytotoxic activity against tumor cells and host immune cells. We have tested the
      hypothesis that allogeneic donor T cells treated with low-dose irradiation will
      facilitate engraftment and mediate an anti-leukemia effect in a mouse model of
      bone marrow transplantation. Multiple infusions of irradiated allogeneic donor
      lymphocytes in the peri-transplant period had graft-enhancing activity without
      resulting in GVHD. Murine recipients of irradiated allogeneic splenocytes and
      allogeneic bone marrow had stable donor-derived hematopoiesis without a
      significant contribution of irradiated donor cells to the T cell compartment.
      Removing T cells from the allogeneic splenocytes prior to irradiation largely
      eliminated their graft facilitating activity. Based upon the promising results of
      the pre-clinical murine studies, we initiated a phase I clinical trial of
      multiple infusions of irradiated allogeneic lymphocytes in patients who had
      relapsed after allogeneic BMT. Of 12 patients treated to date on this study,
      three have shown objective responses of their leukemia or lymphoma to multiple
      infusions of irradiated donor lymphocytes. We have initiated a new phase I
      clinical study to test the efficacy of multiple infusions of irradiated
      allogeneic cytotoxic T cells to facilitate engraftment in allogeneic
      transplantation. Successive cohorts of patients will be transplanted with
      allogeneic stem cells alone, or a combination of allogeneic stem cells and
      increasing numbers of irradiated allogeneic T cells. Irradiated allogeneic
      lymphocytes that retain short-term allo-specific cytotoxicity and lack the
      potential for clonal expansion in vivo can be considered as a novel form of
      immunotherapy with defined pharmacokinetics.

PMID- 10933182
TI  - Autologous and allogeneic stem cell transplantation in multiple myeloma.
AB  - Multiple myeloma is still an incurable disease. The standard conventional
      chemotherapy comprises melphalan and prednisone (MP). Combination chemotherapy
      regimens could not improve the median survival of 36 months observed with MP. In
      the French IFM90 study, HD therapy with TBI plus melphalan 140 mg/m2 was shown to
      prolong overall survival and progression-free survival compared to conventional
      treatment. Nonetheless, most patients eventually succumb due to disease
      progression. Allogeneic transplantation may induce long-term remissions and even
      cure, but is hampered by a high transplantation-related mortality (TRM).
      Currently, efforts are made to reduce this TRM and to evaluate the graft-versus
      myeloma effect.

PMID- 10933183
TI  - A comparative study of peripheral blood stem cell vs bone marrow transplantation
      from unrelated donors (MUD): a single center study.
AB  - Peripheral blood stem cell transplants (PBSCT) from unrelated donors (n = 37)
      were compared with bone marrow transplants (BM, bone marrow group, n = 37) in a
      matched pair analysis. Ten patients (2, class 1) in the alloPBSCT group and seven
      patients (2, class 1) in the BM group had one HLA locus mismatch donor,
      respectively. The following factors were matched: HLA-compatibility, diagnosis,
      disease stage, age and gender. The median age in the PBSC group was 37 years (19
      56, excluding one 6-year-old child) and in the BM group 37 years (18-53). The BM
      group consisted of 12 females and 25 males, 17 females and 20 males were in the
      PBSC group. Twelve patients in the BM and 11 patients in the PBSC group were
      diagnosed with AMI,; 7/7, ALL; 15/15, CML; 2/3, MDS; 1/1, NHL. Thirty-four
      (14/20) of the 74 patients (45%) were considered as high risk patients. The
      conditioning regimen was BU/CY for standard risk patients with myeloid diseases
      (31 patients) and TBI/CY for ALL and NHL patients (36 patients); six patients
      received intensified conditioning with VP16 (2 patients), thiotepa (2 patients)
      or melphalan (1 patient). The GVHD prophylaxis regimen was used according to the
      Seattle protocol. DFS was 51% (19 patients) with a median of 352 days and 59% (21
      patients) with a median of 760 days, in PBSC and BM transplants, respectively.
      The median time to leukocyte engraftment in PBSC patients was 14 days (range 6-26
      days) and in the BM group 19 days (range 9-29 days; P < 0.02). The time of
      platelet engraftment did not differ significantly between the groups. The
      incidence of grade II-IV acute GVHD was 40% (four patients died, 13%) in the PBSC
      group and 20)% (three patients died, 8%) in the BM group, respectively (P < 0.05,
      log-rank). No signs of aGVHD were found in 19% of the patients in the PBSC and
      27% in the BM group. Our results indicate that allogeneic PBSCT does lead to a
      significantly faster leukocyte engraftment. The significant increase with regard
      to the incidence and shorter time of onset of severe aGVHD in PBSC patients,
      compared to marrow transplant patients, need to be confirmed in a randomised
      trial.

PMID- 10933184
TI  - 'Sepsis' and multi-organ failure: predictors of poor outcome after hematopoietic
      stem cell transplantation in children.
AB  - Prognostic scores, such as the PRISM and APACHE II, have been established,
      predicting with reasonable accuracy the outcome of patients admitted to intensive
      care units (ICU). In keeping with previous reports, we found, however, that these
      scores failed to perform in a series of 28 recipients of hematopoietic auto- or
      allografts (BMT) who required ICU admission for reasons including respiratory
      (82%) and multi-organ (36%) failure. We therefore retrospectively analyzed the
      charts of these patients, evaluating predisposing factors and prognostic
      variables which might confound the validity of these ICU tools which in other
      clinical scenarios have proven so valuable. Of all the parameters tested,
      logistic analysis established the following as predictors for poor outcome:
      increased C-reactive protein (CRP) to > 10 mg/dl (P = 0.04), macroscopic
      hemorrhage (P = 0.04), hypotension (mean arterial pressure < normal) (P = 0.04)
      and GVHD > or = III (P = 0.002). Most of these factors are not accounted for by
      the standard prognostic questionnaires. The development of an 'oncological' or
      'post-BMT' risk of mortality score, taking into account these patients' specific
      clinical problems, might improve the risk assessment for this patient group, and
      might thus facilitate the timely recognition of those patients most in need of
      more intensive therapeutic measures.

PMID- 10933186
TI  - Depletion of alloreactive donor T cells using immunomagnetic cell selection.
AB  - Donor T cells support both engraftment and immune reconstitution after allogeneic
      BMT. Moreover, they may exert potent anti-tumor effects (graft-versus-leukemia,
      GVL), which are used for adoptive immunotherapy. On the other hand, infusion of
      allogeneic T cells is frequently associated with the manifestation of immune
      reactions against healthy tissue, which may lead to life-threatening graft-versus
      host disease (GVHD). To overcome this problem, we developed a new strategy for
      the exclusive depletion of alloreactive cells from donor leukocytes. We activated
      donor T cells by co-cultivation with a stroma layer of recipient cells and
      analyzed activation kinetics of CD3+, CD4+ and CD8+ T cells. Based on these data,
      activated cells were then depleted based on expression of activation-induced
      antigens using magnetic cell sorting (MACS). Alloreactivity of donor T cells was
      remarkably decreased after depletion of cells expressing either CD25 or CD69, as
      was shown in suitable in vitro assays. The lowest level of alloreactivity was
      found when both CD25- and CD69-positive cells were depleted. Importantly,
      depleted cell fractions preserved reactivity against third-party cells. In
      summary, we found that MACS-based ex vivo depletion of alloreactive cells may be
      a suitable way to prevent GVHD and therefore improve allogeneic BMT and adoptive
      immunotherapy.

PMID- 10933185
TI  - Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v.
      busulfan and cyclophosphamide (i.v. BuCy).
AB  - Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic
      hematopoietic stem cell transplantation (BMT) was investigated in a phase II
      trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome
      (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy
      60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were
      treated, only eight of whom were in CR1. The rest were either refractory to
      induction chemotherapy (four patients) or in a more advanced stage of their
      disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated.
      Their median age was 41 years (range 21-64). Engraftment to > or =500
      neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the
      median time of neutropenia was only 11 days (range 4-28 days). The most common
      regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including
      BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to
      CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment
      related mortality (TRM) of 5.7%. Three patients developed VOD and two of them
      died. There was no direct regimen-related pulmonary or neurologic toxicity.
      Overall, the clinical side-effect spectrum was analogous to what would be
      expected from a high-dose oral Bu-based regimen; there was no unique toxicity
      experienced with the used solvent system. The disease-free survival in the high
      risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44%
      and 31%, respectively. The 13 patients still alive in CR have been followed for a
      median of 24 months (range 18-32). Pharmacokinetic analysis showed very good
      interdose reproducibility, and limited interpatient variability in area under the
      plasma concentration vs time curve, peak concentration, and clearance of Bu after
      this i.v. formulation. We conclude, that this new i.v. Bu formulation is well
      tolerated; it has an impressive safety profile, and we suggest that it should be
      considered as appropriate replacement for oral busulfan in pretransplant
      conditioning therapy prior to allogeneic BMT for patients with AML or MDS.

PMID- 10933187
TI  - Targeting p53, hdm2, and CD19: vaccination and immunologic strategies.
AB  - Peptides presented by class I major histocompatibility complex (MHC) molecules
      and derived from normal self-proteins that are expressed at elevated levels by
      cells from a variety of human (Hu) malignancies provide, in theory, potential
      target antigens for a broad-spectrum, cytotoxic T lymphocyte (CTL)-based
      immunotherapy of cancer and hematologic malignancies. However, as such tumor- and
      leukemia-associated self-proteins are also expressed at low levels in some types
      of normal tissues, such as thymus, spleen and lymphohemopoietic cells, these self
      MHC-self-peptide complexes may also represent thymic and/or peripheral
      tolerogens, thereby preventing immune responses. This is particularly true for
      class I MHC-peptide complexes expressed by bone marrow-derived cells in the
      thymus, as such expression would cause negative selection of immature thymic T
      cells with high avidity for self-MHC-self-peptide complexes. This intrathymic
      deletion of potentially self-reactive T cells could result in a peripheral T cell
      repertoire purged of CTL precursors with sufficient avidity to recognize natural
      tumor associated self-epitopes presented by class I MHC molecules on tumor cells.
      HLA-transgenic (Tg) mice provide the basis of an experimental strategy that
      exploits species differences between Hu and murine (Mu) protein sequences in
      order to circumvent self-tolerance and obtain HLA-restricted CTL specific for
      epitopes derived from tumor- and leukemia-associated Hu self proteins, such as
      p53, Her-2/neu, hdm2 and CD19.

PMID- 10933188
TI  - Bcr/abl+ autologous dendritic cells for vaccination in chronic myeloid leukemia.
AB  - In chronic myeloid leukemia (CML) ex vivo generated DC are characterized by
      constitutive expression of bcr/abl and possibly other yet undefined leukemia
      associated antigens, since these DC share a common progeny with leukemic cells.
      Induction of anti-leukemic T cell responses has been described in vitro. For a
      phase I vaccination study, autologous bcr/abl+ DC are generated under GMP
      conditions mainly from monocyte precursors in chronic phase CML patients. Lin-,
      CD80+, CD86+, CD83+, DR+ DC could be generated in sufficient numbers for s.c.
      vaccination with 1 x 10(6)-5 x 10(7) DC. Using monocyte precursors, the yield of
      DC per seeded PBMC was in the range of 1-6%. Furthermore, we could demonstrate in
      vitro that the T cell stimulatory ability of CD34+-derived DC can be augmented by
      a factor 2-3 by retroviral transduction with a gene coding for interleukin-7. DC
      based vaccination strategies are a promising clinical approach, particularly as
      postremission immunotherapy in the setting of autologous stem cell
      transplantation.

PMID- 10933189
TI  - Treatment of patients with malignant lymphomas with monoclonal antibodies.
AB  - Malignant lymphomas represent a heterogenous group of B and T cell-derived
      malignancies. Most lymphomas are sensitive to chemo- and radiotherapy, however
      many patients will eventually relapse. Immunotherapeutic approaches including
      monoclonal antibodies, cytokines or vaccination approaches may offer an
      alternative treatment of chemotherapy-resistant residual cells especially in
      cases with low tumor burden or residual disease following chemo- or radiotherapy.
      Monoclonal antibodies have been successfully applied in their native form, or
      coupled with radioisotopes or toxins to selectively destroy lymphoma cells and
      promising results in early clinical trials have been obtained. Alternatively,
      bispecific antibodies and idiotypic vaccination strategies are used to target
      autologous T cells to eliminate lymphoma cells. A humanized anti-CD20 antibody
      showed excellent results in chemotherapy refractory lymphomas and has recently
      been approved for clinical application in CD20 positive B cell lymphomas.

PMID- 10933190
TI  - Immunotherapy of hematologic malignancies and metastatic solid tumors in
      experimental animals and man.
AB  - Following engraftment of donor hematopoietic cells and induction of host-versus
      graft tolerance, immunocompetent lymphocytes of donor origin can induce graft
      versus-leukemia (GVL) and graft-versus-tumor (GVT) effects. Engraftment of
      allogeneic bone marrow cells can be accomplished following non-myeloablative
      conditioning while possibly controlling graft-versus-host disease (GVHD). GVL and
      GVT effects may thus be successfully accomplished following non-myeloablative
      stem cell transplantation (NST) as shown by data derived from experimental
      animals and man.

PMID- 10933191
TI  - Unrelated cord blood transplantation vs matched unrelated donor bone marrow
      transplantation: the risks and benefits of each choice.
AB  - Matched sibling BMT is the treatment of choice for many malignant and non
      malignant diseases. Unfortunately, donor availability limits its applicability
      with only approximately one-third of patients having HLA-matched family members.
      For the remaining two-thirds of patients who need an allogeneic procedure, an
      alternative donor is required. Matched unrelated donor (MUD) bone marrow
      transplants have proven useful for many of these patients, however, matched
      donors may be unavailable or too time-consuming to find. In addition, MUD
      transplants are associated with high morbidity and mortality secondary to severe
      graft-versus-host disease (GVHD), organ toxicity, and infections. For those
      patients without a matched related or unrelated volunteer donor, unrelated
      umbilical cord blood transplantation (UCBT) is a feasible alternative. UCBT has
      been associated with a lower incidence and severity of GVHD than MUD BMT,
      allowing successful transplantation in the HLA-mismatched setting, thus
      increasing the donor pool. This manuscript reviews the available literature
      regarding these two procedures, assesses their risk/benefit ratio, and arrives at
      several conclusions regarding their relative indications.

PMID- 10933192
TI  - Evaluation of engraftment of ex vivo expanded cord blood cells in humans.
AB  - Cord blood transplants (CBT) result in high rates of engraftment in patients
      transplanted because of inherited diseases even across marked HLA disparities,
      mostly in children, with less severe manifestations of GVHD than BM and PBSC
      transplants. Evaluation of engraftment potential of CBT based on early progenitor
      content is difficult due to their inaccurate quantification. Instead, post-thaw
      nucleated cell counts (Pt-NCC) are commonly used for this purpose. We have
      analyzed engraftment as a function of pre-freeze nucleated cell counts (Pf-NCC)
      in patients receiving CBT because of inherited diseases. We have observed median
      times to engraftment of 26 days or less, shortest times ranging 8 to 13 days,
      late engraftment or graft failures tending to be associated with age >15 years
      and infusions of <3.7 x 10(7)/Pf-NCC/kg. These data may be appropriate references
      to evaluate engraftment of CBT performed with previously ex vivo expanded cells.
      CBT performed with units of which one aliquot has been previously culture
      expanded have resulted in times to engraftment similar to the ones observed in
      the above-mentioned analysis. In these trials it is not possible to trace the
      actual origin of the early engrafting cells because the pre-cultured cells lack
      differentiating markers. To better evaluate the engraftment dynamics of culture
      expanded CB cells in humans, we have used a model of simultaneously transplanting
      cells from two different donors to the same patient. Preliminary results of
      patients that have simultaneously received one uncultured CB unit and culture
      expanded purified CB CD34+ cells obtained from a second one show no significant
      contribution of cultured cells to early engraftment, and no prohibitive
      unfavorable immunological problems have been observed.

PMID- 10933194
TI  - Genetic modification of haematopoietic cells for combined resistance to
      podophyllotoxins, other agents covered by MDR1-mediated efflux activity and
      nitrosoureas.
AB  - Genetic transfer and expression of drug-resistance functions into haematopoietic
      stem and progenitor cells is a promising means to overcome both the acute and
      longterm side-effects of cytotoxic drugs in bone marrow. Here, we describe a
      functional analysis of a retroviral vector that co-expresses human cDNAs for
      multidrug resistance 1/P-glycoprotein (MDR1) and a double mutant of O(6)
      alkylguanine-alkyltransferase (hATPA/GA) to high levels. The hATPA/GA protein
      contains two amino acid substitutions that render it resistant to compounds such
      as O(6)-benzylguanine that inhibit the wild-type protein which is often
      overexpressed in resistant tumour cells. Evidence for simultaneous drug
      resistance of genetically modified primary murine progenitor cells to colchicine
      or the podophyllotoxin etoposide, both covered by MDR1-mediated efflux activity,
      and the nitrosourea BCNU, which is counteracted by hATPA/GA, is presented using
      in vitro colony assays.

PMID- 10933193
TI  - Cord blood transplantation and cord blood bank in Japan.
AB  - The first cord blood transplantation (CBT) was performed in a 5-year-old boy with
      acute myelogenous leukemia from his HLA-identical sibling donor in 1994. Since
      then there have been 17 related and 131 unrelated CBTs in Japan. Overall survival
      and disease-free survival (DFS) were over 70% in sibling donor CBT. DFS of
      unrelated CBT in leukemia and other hematological malignancies was 43%, and OS of
      UCBT in non-malignant diseases was 63%. HLA disparity between the donor and the
      recipient did not affect the incidence and severity of acute graft-versus-host
      disease (GVHD) or survival. Cell dose was the most important factor for
      engraftment and survival both in malignant and in non-malignant diseases. The
      Japanese government has recently established the nationwide cord blood bank
      network, and eight local cord blood banks are financially supported by the
      government. 20,000 units of CB are planned to be collected and stored in the next
      5 years by this network.

PMID- 10933196
TI  - Development of a cytomegalovirus vector for somatic gene therapy.
AB  - The development of new and improved vector systems is central for realization of
      new concepts for gene therapy. The tropism of human cytomegalovirus (CMV) for
      hematopoietic progenitor cells and the large genome size (230 kbp) that offers a
      unique cloning capacity make this virus a promising vector candidate for gene
      transfer into hematopoietic cells and for therapy of congenital and acquired
      diseases of the hematopoietic system. Recently, we cloned the CMV genome as a
      bacterial artificial chromosome (BAC) in Escherichia coli and established
      efficient mutagenesis procedures for CMV - a prerequisite for vector
      construction. Here, we report on the construction of a recombinant GFP virus that
      will be used to re-evaluate the tropism of CMV and to monitor gene transfer into
      target cells. Further goals of CMV vector development are the evaluation of the
      cloning capacity and the construction of replication-deficient vectors.

PMID- 10933195
TI  - Amphotropic and VSV-G-pseudotyped retroviral vectors transduce human
      hematopoietic progenitor cells with similar efficiency.
AB  - One restriction of retroviral gene transfer into hematopoietic stem cells is the
      low level of amphotropic virus receptor. In the present study, we examined
      whether retroviral vectors pseudotyped with the G-protein of vesicular stomatitis
      virus (VSV) can overcome this restriction. Human progenitor cells purified by
      magnetic beads and cell sorting were transduced with an amphotropic or VSV-G
      pseudotyped retroviral vector containing the truncated human nerve growth factor
      receptor as a marker gene. Cells were prestimulated with flt-3 ligand, stem cell
      factor, and interleukin-3 and transduced on fibronectin. Marker gene expression
      was analyzed by flow cytometry. Transduction efficiencies of amphotropic and VSV
      G-pseudotyped virus for CD34+ cells did not differ significantly. Gene transfer
      into CD34+CD38- cells, which are enriched in more immature progenitors, was not
      restricted and transfer efficiencies for this subset were also similar for both
      pseudotypes. The addition of fibronectin improved gene transfer with the
      amphotropic vector considerably (5- to 19.3-fold, mean 12.6), while the effect on
      the VSV-G-pseudotype was far less pronounced (1- to 3.9-fold, mean 2.1, P =
      0.04). In conclusion, high levels of gene transfer to human hematopoietic
      progenitors were achieved with an optimized transduction protocol, and
      transduction efficiencies could not be improved further by the use of VSV-G
      pseudotypes.

PMID- 10933197
TI  - Allogeneic vaccination for renal cell carcinoma: development and monitoring.
AB  - An allogeneic tumor cell vaccine should display a natural immunogenicity that
      allows the stimulation of tumor-reactive effector cells in patients. Furthermore,
      the vaccine should express antigens that are shared by many tumors to which
      patients are not tolerant. A variety of tumor peptides should be presented by
      different HLA-molecules due to limited MHC matching with recipients and last but
      not least, the vaccine should have a strong growth potential in vitro to allow
      adequate amounts of vaccine to be generated for long-term usage. In vitro and in
      situ studies with the renal cell carcinoma cell line RCC-26 demonstrate: (1) RCC
      26 can induce complex allospecific responses through direct priming; (2) RCC-26
      can not only reactivate cytotoxic T lymphocytes (CTL) of a memory phenotype but
      they also can induce de novo tumor-antigen associated responses in normal donors;
      (3) these cells present epitopes restricted by several MHC molecules, allowing
      the vaccination of patients matched for different HLA alleles; and (4) they
      stimulate HLA-A*0201-restricted T cells bearing characteristic T cell receptors
      (TCR). Thus, in addition to using limiting dilution killer and ELISPOT assays,
      molecular tracking of a tumor-specific TCR can be used to judge the development
      of antitumor reactivity and vaccine efficiency.

PMID- 10933198
TI  - Functional deficiencies of components of the MHC class I antigen pathway in human
      tumors of epithelial origin.
AB  - An association between oncogenic transformation and repression of different
      components of the MHC class I antigen processing machinery (APM) have been
      described in murine model systems. In order to discover whether a similar
      correlation exists, human tumor cell lines of distinct histology with altered ras
      protein were analyzed for the expression of APM components utilizing RT-PCR and
      Western blot analyses. A heterogeneous expression pattern of MHC class I
      antigens, TAP peptide transporter, proteasome subunits, proteasome activator PA28
      and the chaperones calnexin, calreticulin as well as tapasin was displayed by
      these tumor cell lines. Single or combined deficiencies in the expression and/or
      function of TAP, LMP2, LMP10 and tapasin were demonstrated in 11 of 12 cell lines
      studied, whereas the expression of calnexin, calreticulin, beta2-microglobulin,
      LMP7 and PA28alpha was unaltered or only weakly decreased. The impaired
      expression of TAP, LMP subunits and tapasin was not associated with altered ras,
      but resulted in reduced MHC class I surface expression. In particular, a
      significant allele- and locus-specific downregulation of the HLA-A and HLA-B
      haplotypes was found. IFN-gamma treatment corrected the TAP, LMP and tapasin
      deficiencies and enhanced the constitutive PA28alpha, LMP7, calnexin and
      calreticulin expression which was accompanied with increased levels of MHC class
      I antigens. Thus, dysregulation rather than structural alterations of different
      APM components might be one mechanism of colon carcinoma, small cell lung
      carcinoma and pancreatic carcinoma cell lines to evade immune recognition.

PMID- 10933199
TI  - Retroviral transduction of T lymphocytes for suicide gene therapy in allogeneic
      stem cell transplantation.
AB  - Transplantation of suicide gene modified allogeneic T lymphocytes is an approach
      to prevent T cell mediated GVHD while preserving the 'graft-versus-leukemia'
      (GVL) effect of an allograft. A prerequisite for such a therapy is the efficient
      transduction of T cells with suitable vectors. Since existing techniques allow
      only insufficient transduction of T cells, the development of more efficient gene
      transfer protocols into these cells is of great importance. We present here a
      protocol for the highly efficient transduction of human primary T cells at high
      densities (1 x 10(6) cells/ml) by retroviral infection. The presented protocol
      allowed us to obtain transduction rates of more than 70% of CD3+ cells after two
      cycles of infection. It is based on the use of FBS-free media for both the
      production of retrovirus-containing supernatant, as well as the cultivation of
      the primary T cells. Since the protocol presented here works just as efficiently
      under large scale conditions, it may easily be adapted to clinical needs and
      'good manufacturing practice' (GMP) standards.

PMID- 10933200
TI  - Gene therapy of chronic granulomatous disease.
AB  - Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder which
      results from absence or malfunction of the respiratory burst oxidase normally
      expressed in neutrophils and other phagocytic leukocytes. Two-thirds of the
      patients are males hemizygous for mutations in the X-linked gene coding for gp91
      phox. As a therapeutic approach towards the X-linked form of CGD bicistronic
      retroviral vectors containing the gp91-phox gene and a selectable marker gene
      were constructed. The ability of these vectors to restore NADPH oxidase activity
      was tested in a human myeloid leukemic cell line that is defective in superoxide
      production, as well as in primary CD34+ cells obtained from X-CGD patients. Under
      optimal conditions 80% of the CD34+ cells derived from bone marrow of one X-CGD
      patient were transduced. The level of superoxide production, in phagocytes
      derived from transduced cells was 68.9% of normal levels. Considering that low
      levels of superoxide generating activity are sufficient for normal host defense,
      the present experiments provide the basis for the development of a gene
      replacement therapy for the X-linked form of CGD.

PMID- 10933201
TI  - Protection of hematopoietic cells against combined O6-benzylguanine and
      chloroethylnitrosourea treatment by mutant forms of O6-methylguanine DNA
      methyltransferase.
AB  - This report demonstrates that expression of the P140A O6-methylguanine DNA methyl
      transferase (MGMT) mutant via retrovirus-mediated gene transfer leads to
      significant, but modest, resistance of cells to both 6-benzylguanine (6-BG)
      depletion and treatment with 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU).
      Expression of the P140A/G156A double mutant appeared to be associated with
      reduced or unstable protein in hematopoietic cells.

PMID- 10933202
TI  - Engineering drug resistance in human cells.
AB  - Many of the problems with current anti-tumour therapies stem from a lack of
      specificity for tumour as opposed to normal tissues. To address the problem of
      collateral toxicity during anti-tumour chemotherapy we have been developing a
      gene therapy approach to protect normal tissues from the toxic and potentially
      mutagenic effects of chemotherapeutic agents. As a paradigm for this we have been
      examining the potential of the DNA repair protein O6-alkylguanine-DNA
      alkyltransferase (ATase) to confer genetic chemoprotection to the bone marrow. By
      transfer and expression of a mutant form of this protein, which is resistant to
      inactivation by the tumour sensitising agent O6-benzylguanine (O6-beG), we have
      been able to demonstrate protection of murine bone marrow in vitro from the
      cytotoxic and clastogenic effects of O6-beG in combination with the anti-tumour
      agent temozolomide. This protection is seen in multiple lineages, including
      erythroid and granulocyte/macrophage progenitors, as well as more primitive
      cells. Importantly, significant protection of the platelet lineage is also seen,
      with faster recovery of platelets. The multi-lineage protection seen has
      encouraged us to take this approach forward to clinical trial in the near future.

PMID- 10933203
TI  - Clinical scale production of an improved retroviral vector expressing the human
      multidrug resistance 1 gene (MDR1).
AB  - Retroviral vectors are currently the most important and best characterized tools
      for ex vivo genetic modification of hematopoietic progenitor/stem cells. As a
      prerequisite for clinical applications, large volumes of high-titer vector
      supernatants have to be generated in compliance with 'GMP' guidelines. This goal
      can be reached using a carefully selected producer cell clone and a conventional
      large-scale cell culture system. The retroviral vector SF1m provides efficient
      expression of the human multidrug resistance 1 (MDR1) gene in hematopoietic
      progenitor/stem cells in vitro and in NOD/SCID mouse repopulating human cells in
      vivo. Currently, a clinical phase I/II study is in preparation to test whether
      intensified consolidation chemotherapy is enabled by autologous transplantation
      of peripheral blood progenitor/stem cells that have been genetically modified
      with SF1m. Using multi-tray cell factories >19 l of serum-free vector containing
      supernatant were generated from cells of a previously established SF1m-producer
      clone, based on the PG13 packaging cell line. Testing of the final samples
      revealed sufficient quality (>1.5 x 10(6) infectious particles/ml) for clinical
      scale transduction of CD34+ cells. Results from the production runs and the
      applied biosafety concept are described.

PMID- 10933204
TI  - Human multidrug resistance-1 gene transfer to long-term repopulating human
      mobilized peripheral blood progenitor cells.
AB  - Mobilized peripheral blood progenitor cells (PBPC) are an attractive target for
      the retrovirus-mediated transfer of cytostatic drug resistance genes. We analyzed
      NOD/SCID mouse repopulating CD34+ PBPC from cancer patients following retroviral
      Transwell transduction in various cytokine combinations with the FMEV-based
      (Friend-mink cell focus forming/murine embryonic stem cell virus) hybrid vector
      SF-MDR carrying the human multidrug resistance-1 (MDR1) gene. Five to 10 weeks
      following transplantation of 2.0 x 10(6) CD34+ PBPC into NOD/SCID mice we
      observed medium to high levels of human cell engraftment with up to 33%. The
      extent of vector-marked human cells was assessed by a quantitative real-time
      polymerase chain reaction (PCR). SF-MDR gene transfer into long-term in vivo
      repopulating human hematopoietic cells was optimal in the presence of either IL
      3/IL-6/SCF/FL or FL/TPO/SCF resulting in three-fold (12.4% +/- 1.7%) or four-fold
      (16.5% +/- 6.8%) higher average proportions of gene-marked human cells in
      NOD/SCID mice as compared to IL-3 alone (P < 0.01). In conclusion, we could
      optimize the engraftment capacity and the retroviral gene transfer to CD34+ PBPC
      using cocktails of early acting cytokines in combination with the recombinant
      fibronectin fragment CH-296. Our data suggest that the NOD/SCID model provides a
      valid assay to estimate the gene transfer efficiency to repopulating human PBPC
      that may be achievable in clinical autologous transplantation settings.

PMID- 10933205
TI  - Prefrontal cortical contributions to working memory: evidence from event-related
      fMRI studies.
AB  - Working memory refers to the short-term retention of information that is no
      longer accessible in the environment, and the manipulation of this information,
      for subsequent use in guiding behavior. In this review, we will present data from
      a series of event-related functional magnetic-resonance-imaging (fMRI) studies of
      delayed-response tasks that were designed to investigate the role of different
      regions of the prefrontal cortex (PFC) during different working-memory component
      processes. From these data, we conclude that: (1) lateral PFC is anatomically
      organized according to the types of cognitive operations that one performs when
      attempting to temporarily maintain and manipulate information; and (2) consistent
      with the picture that has emerged from the monkey electrophysiological
      literature, human lateral PFC is involved in several encoding- and response
      related processes as well as mnemonic and nonmnemonic processes that are engaged
      during the temporary maintenance of information. Thus, lateral PFC activity
      cannot be ascribed to the function of a single, unitary cognitive operation.

PMID- 10933206
TI  - Object working memory and visuospatial processing: functional neuroanatomy
      analyzed by event-related fMRI.
AB  - We report an event-related functional magnetic-resonance-imaging (fMRI)
      experiment that investigates the relationship of transient visual object memory,
      visuospatial orienting, and object recognition. Delayed object matching and
      visuospatial orienting involved a highly overlapping network of brain areas.
      Common areas were the frontal eye fields (FEF), the pre-supplementary motor area
      (pre-SMA)/SMA complex, the precentral gyri, and the horizontal and descending
      branches of the intraparietal sulcus (IPS). Selective delay activation was
      observed anterior to the FEF and in the ascending part of the IPS. Right
      dorsolateral prefrontal cortex was involved in goal-directed visual search, but
      showed no delay activity.

PMID- 10933207
TI  - Segregation of working memory functions within the dorsolateral prefrontal
      cortex.
AB  - It is now widely accepted that the prefrontal cortex (PFC) plays a critical role
      in the neural network subserving working memory (WM). At least three related
      questions are still under debate: (1) is the PFC critical for all constituent
      processes of WM (i.e., short-term storage, manipulation, and utilization of
      mental representations) or only in one or a few of them? (2) Is there segregation
      of function among different cytoarchitectonic subdivisions of the PFC? (3) If
      this be the case, is this segregation based on the nature of the information
      being processed or on the type of cognitive operation performed? The present
      review article describes findings in the monkey supporting a modular "domain
      specific" model of PFC functional organization with respect to WM operations. In
      this model, the dorsolateral prefrontal cortex (DLPFC) is composed of several
      subregions, based primarily on the nature of the information being processed in
      WM. Storage and processing functions are integrally related in each area. Future
      studies designed to map as yet uncharted areas of prefrontal cortex with refined
      anatomical and physiological approaches may provide a critical test of the model
      and evaluate the extent to which it applies generally or, instead, mainly to
      visual domains or only to dorsolateral convexity areas.

PMID- 10933208
TI  - The role of the lateral frontal cortex in mnemonic processing: the contribution
      of functional neuroimaging.
AB  - Evidence is now converging which suggests that, at the area level, working-memory
      processes within the dorsolateral and ventrolateral frontal cortices are
      organised according to the type of processing required, rather than according to
      the nature (i.e. domain) of the information being processed, as has been widely
      assumed. In a recent study using functional magnetic-resonance imaging (fMRI),
      performance of visual spatial and visual non-spatial working-memory tasks was
      shown to involve identical regions of the lateral prefrontal cortex when all
      factors unrelated to the type of stimulus material were appropriately controlled.
      These results concur fully with recent reviews of the imaging literature, which
      demonstrate that spatial, visuospatial and verbal working-memory studies have
      produced distributed patterns of overlapping activation foci within these lateral
      frontal regions. Moreover, two recent positron-emission tomography studies have
      demonstrated that either, or both, the ventrolateral and dorsolateral frontal
      regions can be activated in spatial working-memory tasks, depending on the
      precise executive processes that are called upon by the task being performed.
      Similarly, when the executive requirements of a simple verbal working-memory task
      (e.g. forwards versus backwards digit span) are manipulated, differential
      activation within these two frontal cortical areas is observed. The results
      provide further evidence that the mid-dorsolateral and mid-ventrolateral frontal
      cortical areas make distinct "executive" contributions to memory and correspond
      with a fractionation of working-memory processes in psychological terms.

PMID- 10933209
TI  - The role of the mid-dorsolateral prefrontal cortex in working memory.
AB  - Recent studies with nonhuman primates have shown that lesions of the mid
      dorsolateral prefrontal cortex, which extends from the lip of the dorsal bank of
      the sulcus principalis to the midline (i.e., dorsal area 46 and 9/46 and area 9),
      give rise to severe and long-lasting impairments on self-ordered and externally
      ordered tasks designed to tax executive processing within working memory, rather
      than short-term memory per se. Lesions limited to area 9 give rise to a mild
      impairment on these tasks. Thus, the mid-dorsolateral prefrontal region has been
      shown to be critical for the monitoring of multiple events in working memory. The
      mid-dorsolateral prefrontal region receives visuospatial input from the posterior
      dorsolateral region (areas 8 and 6) and from the cortex within the middle part
      (sulcal area 46) and the caudal part (area 8) of the sulcus principalis.
      Nonspatial visual input originates from the ventrolateral prefrontal cortex.
      Thus, lesions focused on the middle to caudal part of the sulcus principalis
      would affect visuospatial input, but would not affect the flow of nonspatial
      visual object information that reaches the mid-dorsolateral prefrontal region
      from the ventrolateral prefrontal cortex. Lesions of the sulcus principalis
      produce a spatially selective impairment, whereas lesions of the mid-dorsolateral
      prefrontal region produce a more general impairment of the monitoring and
      manipulation of information in working memory. The results of recent functional
      neuroimaging studies with human subjects are consistent with the above findings
      from work with the monkey.

PMID- 10933210
TI  - Functional connectivity of the anterior cingulate cortex within the human frontal
      lobe: a brain-mapping meta-analysis.
AB  - A database of positron-emission-tomography studies published between January 1993
      and November 1996 was created to address several questions regarding the function
      and connectivity of the human anterior cingulate cortex (ACC). Using this
      database, we have previously reported on the relationship between behavioural
      variables and the probability of blood-flow response in distinct subdivisions of
      the ACC. The goal of the current analysis was to discover which areas of the
      frontal cortex show increased blood-flow co-occurring consistently with increased
      blood-flow in the ACC. Analyses of the frequency distributions of peaks in the
      ACC and the remaining frontal cortex (FC) yielded several important findings.
      First, FC peaks in the precentral gyrus, superior frontal gyrus, middle frontal
      gyrus, inferior frontal gyrus, medial frontal gyrus and orbitomedial frontal gyri
      were more frequent in subtractions that also yielded a peak in the ACC than in
      those that did not yield an ACC peak. Second, regional differences in the
      frequency distribution of these FC peaks were observed when the ACC peaks were
      subdivided into the rostral versus caudal ACC and supracallosal versus
      subcallosal ACC. Peaks in the precentral gyrus and in the vicinity of the
      supplementary motor area were more prevalent in subtractions with co-occurring
      peaks in the caudal than with the rostral ACC. Peaks in the middle frontal gyrus
      were more frequent in subtractions with co-occurring peaks in the paralimbic part
      of the supracallosal ACC, relative to the subcallosal or limbic supracallosal
      ACC. These observations are consistent with known differences in the anatomic
      connectivity in these cortical regions, as defined in non-human primates. Further
      analyses of the influence of behavioural variables on the relationships between
      the ACC and other regions of the frontal cortex suggested that this type of meta
      analysis may provide testable hypotheses about functional and effective
      connectivity within the human frontal lobe.

PMID- 10933211
TI  - Executive frontal functions.
AB  - This chapter presents a conceptual model of the representational and executive
      functions of the cortex of the frontal lobe derived from empirical evidence
      obtained principally in the monkey. According to this model, the neuronal
      networks of the frontal lobe that represent motor or executive memories are
      probably the same networks that cooperate with other cerebral structures in the
      temporal organization of behavior. The prefrontal cortex, at the top of the
      perception-action cycle, plays a critical role in the mediation of contingencies
      of action across time, an essential aspect of the temporal organization of
      behavior. That role of cross-temporal mediation is based on the interplay of two
      short-term cognitive functions: one retrospective, of short-term memory or
      sensory working memory, and the other prospective, of attentive set (or motor
      working memory). Both appear represented in the neuronal populations of
      dorsolateral prefrontal cortex. At least one of the mechanisms for the retention
      of working memory of either kind seems to be the reentry of excitability through
      recurrent cortical circuits. With those two complementary and temporally
      symmetrical cognitive functions of active memory for the sensory past and for the
      motor future, the prefrontal cortex secures the temporal closure at the top of
      the perception-action cycle.

PMID- 10933212
TI  - Control of action as mediated by the human frontal lobe.
AB  - Conscious control of action involves the voluntary initiation and the continuous
      adjustment of motor activity. Neuroimaging data provide evidence that the plan
      for a movement is developed with respect to the behavioral context in prefrontal
      cortex, while the synergies of a motor program are coded by premotor cortex and
      the specific movement parameters by the motor cortex. It is suggested that the
      initiational aspects of conscious motor activity are implemented in a medial
      system of information flow and the integrative aspects in a lateral system of the
      human frontal lobe.

PMID- 10933213
TI  - One more cup of coffee for the road: object-action assemblies, response blocking
      and response capture after frontal lobe damage.
AB  - We report data from a patient, FK, who manifested 'utilisation' behaviour after
      bilateral lesions of the medial frontal and anterior temporal lobes. In tasks
      requiring actions to be made with the hand compatible with the orientation of a
      cup, FK was able to ignore irrelevant distractors that fell in the path of action
      to the target. However, errors were made when the distractors were other cups.
      These errors reflected the hand selected on the basis of the properties of the
      target, suggesting that distractors competed to control the action after
      selection of the target. When similar in kind to the target, distractors
      sometimes captured the action. However, distractors that were associated with an
      action related to the target blocked the usual hand response. These results
      suggest a complex interlocking of attention and action when grasping responses
      are made to a target amongst distractors. There is initial selection of the
      target, but distractors on the path of a reach can then compete for control of
      the action. Distractors can be inhibited if they do not match the properties of
      the specified target, and there can also be inhibition of concurrently activated
      responses. We show that the magnitude of the inhibition is proportional to the
      strength of learned object-action associations.

PMID- 10933214
TI  - Massive impairment in executive functions with partial preservation of other
      cognitive functions: the case of a young patient with severe degeneration of the
      prefrontal cortex.
AB  - Historical bases for the special role of the prefrontal cortex are outlined and
      the case of a 27-year-old woman with massive bilateral prefrontal damage of
      unknown etiology is then described. Frontal lobe degeneration was repeatedly
      examined with magnetic resonance imaging and fluoro-deoxy-D-glucose-positron
      emission tomography and was found to include both orbital and dorsolateral
      aspects of the frontal lobes. While the degeneration initially measured was
      limited to portions of the orbital, medial and dorsolateral parts of both frontal
      lobes, with right-sided predominance, a second brain scan 15 months later
      revealed massive shrinkage of both frontal lobes, together with additional
      involvement of the posterior association cortices. The patient had completed her
      high-school education and had superior verbal long-term memory, normal short-term
      memory, and normal priming, but manifested grossly deficient scores in various
      frontal lobe-sensitive tests. Though a number of neurological examinations were
      performed, no plausible cause for the damage was established.

PMID- 10933215
TI  - Specialisation within the prefrontal cortex: the ventral prefrontal cortex and
      associative learning.
AB  - This paper provides evidence that the ventral prefrontal cortex plays a role in
      the learning of tasks in which subjects must learn to associate visual cues and
      responses. Imaging with both positron-emission tomography (PET) and functional
      magnetic-resonance imaging (fMRI) reveals learning-related increases in activity
      when normal subjects learn visual associative tasks. Evidence is also presented
      from an event-related fMRI study that activity in this area is time-locked both
      to the presentation of the visual stimuli and also to the time of the motor
      response. Finally, it is shown in a study of monkeys that removal of the ventral
      prefrontal area 12 (including 45 A) impairs the ability of monkeys to relearn a
      visual associative task (visual matching), even though there were no demands on
      working memory. It is, therefore, proposed that the ventral prefrontal cortex
      constitutes part of the circuitry via which associations are formed between
      visual cues and the actions or choices that they specify. On the basis of the
      existing anatomical and electrophysiological data, it is argued that the
      prefrontal cortex is the only area that can represent cues, responses and
      outcomes.

PMID- 10933216
TI  - Role of prefrontal cortex in a network for arbitrary visuomotor mapping.
AB  - In arbitrary visuomotor mapping, an object instructs a particular action or
      target of action, but does so in a particular way. In other forms of visuomotor
      control, the object is either the target of action (termed standard mapping) or
      its location provides the information needed for targeting (termed
      transformational mapping). By contrast, in arbitrary mapping, the object's
      location bears no systematic spatial relationship with the action.
      Neuropsychological and neurophysiological investigation has, in large part,
      identified the neural network that underlies the rapid acquisition and
      performance of arbitrary visuomotor mappings. This network consists of parts of
      the premotor (PM) and prefrontal (PF) cortex, the hippocampal system (HS), and
      the basal ganglia (BG). Here, we propose specialized contributions of the
      network's different components to its overall function. To do so, we invoke the
      concept of distributed information-processing architectures, or modules, which
      may involve a variety of neural structures. According to this view, recurrent
      neural networks involving cortex, basal ganglia, and thalamus operate largely in
      parallel. Each of these interacting networks can be termed a cortical-BG module.
      A large number of these modules include PM neurons, and they can be termed PM
      cortical-BG modules. A comparable number include PF neurons, termed PF cortical
      BG modules. We propose that PM and PF cortical-BG modules compute specific object
      to-action mappings, in which the network learns the action associated with a
      given input. These mappings serve as specific solutions to arbitrary visuomotor
      mapping problems. However, they are also exemplars of more abstract rules, such
      as the knowledge that nonspatial visual information (e.g., color) can guide the
      choice of action. We propose that PF cortical-BG modules subserve abstract rules
      of this kind, along with other problem-solving strategies. This view should not
      be taken to imply that the PF network lacks the capacity to compute specific
      mappings, but rather that it has higher-order mapping functions in addition to
      its lower-order ones. Furthermore, it seems likely that PF provides PM with
      pertinent sensory information. The hippocampal system appears to play a role
      parallel to that of both neocortical-BG networks discussed here. However, in
      accord with several models, it operates mainly in the intermediate term, pending
      the consolidation of the relevant information in those neocortical-BG networks.

PMID- 10933217
TI  - Chemical neuromodulation of frontal-executive functions in humans and other
      animals.
AB  - Neuromodulation of frontal-executive function is reviewed in the context of
      experiments on rats, monkeys and human subjects. The different functions of the
      chemically identified systems of the reticular core are analysed from the
      perspective of their possible different interactions with the prefrontal cortex.
      The role of dopamine in spatial working memory is reviewed, taking account of its
      deleterious as well as facilitatory effects. Baseline-dependent effects of
      dopaminergic manipulation are described in rats on an attentional task, including
      evidence of enhanced function following infusions of D1 receptor agonists into
      the prefrontal cortex. The precise nature of the cognitive task under study is
      shown to be a powerful determinant of the effects of mesofrontal dopamine
      depletion in monkeys. Parallels are identified in human subjects receiving drugs
      such as the indirect catecholamine agonists L-dopa, methylphenidate and the
      dopamine D2 receptor blocker sulpiride. The effects of these drugs on different
      types of cognitive function sensitive to frontal lobe dysfunction are contrasted
      with those of a manipulation of 5-HT function, dietary tryptophan depletion.
      Hypotheses are advanced that accord the ascending systems a greater deal of
      specificity in modulating prefrontal cortical function than has hitherto been
      entertained, and clinical and theoretical implications of this hypothesis are
      discussed.

PMID- 10933218
TI  - The metencephalic floor plate of chick embryos expresses two secretory
      glycoproteins homologous with the two glycoproteins secreted by the
      subcommissural organ.
AB  - The nature and the function of the compounds secreted by the floor plate (FP) of
      the metencephalon are little known. The FP cells of the hindbrain react with
      antibodies (AFRU) against the glycoproteins secreted by the subcommissural organ
      (SCO). One of the these proteins, RF-Gly I, is a 540-kDa core glycosylated
      protein. The aims of the present investigation were to identify by immunoblot the
      AFRU-immunoreactive compound secreted by the FP of chick embryos, to establish
      temporal and regional patterns of this secretory activity, and to obtain
      information about the fate of these compounds. It was established that the SCO
      and FP of chick embryos secrete two AFRU-immunoreactive compounds of 540 and 230
      kDa. The two compounds secreted by the FP have been designated as FP-Gly I and FP
      Gly II. The expression of these proteins was circumscribed to the metencephalic
      FP, and occurred from HH 29 to HH 36. Within the FP cells, FP-Gly I and FP-Gly II
      were confined to the supranuclear and apical regions, which under the electron
      microscope displayed numerous cisternae of the rough endoplasmic reticulum and
      granules. Aggregates of AFRU-immunoreactive material appeared on the free surface
      of the FP. The possibility that FP-Gly I and FP-Gly II are released into the
      ventricle to reach distant targets is discussed.

PMID- 10933219
TI  - Expression of the janus kinases-signal transducers and activators of
      transcription pathway in Hassall's corpuscles of the human thymus.
AB  - The janus kinases (JAK) and signal transducers and activators of transcription
      (STAT) pathway has been shown to play a key role in cytokine-mediated signal
      transduction, and to regulate growth, differentiation, and death of both normal
      and transformed cells. In the present study, we investigated
      immunohistochemically the distribution of the JAK-STAT pathway in the human
      thymus. Various elements of the pathway were abundantly expressed in Hassall's
      corpuscles, located in the thymus medulla and representing terminal stages of the
      thymic medullary epithelium. Furthermore, the elements of the pathway showed
      distinct localization in Hassall's corpuscles. JAK1, JAK2, and TYK2 were
      expressed in high amounts in the entirety of Hassall's corpuscles, whereas JAK3
      was in the outer layer. STAT1, STAT2, and STAT6 were abundantly expressed in the
      entire Hassall's corpuscles, whereas STAT5 was in the outer layer. These findings
      strongly suggest that the JAK-STAT pathway may play a role in thymic medullary
      epithelial maturation.

PMID- 10933220
TI  - Spermatogenesis proceeds normally in mice without linker histone H1t.
AB  - The histone gene H1t is expressed exclusively in pachytene spermatocytes of the
      testis. In this report we have eliminated the single copy H1t gene by homologous
      recombination from the mouse genome to analyse the function of the H1t protein
      during spermatogenesis. Mice homozygous for the mutated H1t gene locus developed
      normally and showed no anatomic abnormalities until the adult stage. In addition,
      H1t-deficient mice were fertile and reproduced as wild-type mice. The process of
      spermatogenesis and the testicular morphology remained unchanged in the absence
      of H1t. RNase protection analysis demonstrated that H1.1, H1.2 and H1.4 histone
      gene expression is enhanced during spermatogenesis in H1t-deficient mice.

PMID- 10933221
TI  - Expression of matrix metalloproteinases and their inhibitors during hepatic
      tissue repair in the rat.
AB  - Matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) are
      thought to play an essential role in liver injury associated with tissue
      remodeling. However, their distinct expression profile in different liver repair
      models still remains to be established. Hepatic expression of collagenase (MMP
      13), gelatinases A and B (MMP-2, -9), stromelysin-1 and -2 (MMP-3, -10), membrane
      type MMP-1 (MMP-14), and TIMP-1 and -2 was studied following single and repeated
      CCl4-mediated injury and after partial hepatectomy. Expression was analyzed by
      reverse transcription-PCR (RT-PCR), northern blot analysis, zymography, and
      immunohistochemistry. Following a single toxic liver injury, MMPs and TIMPs were
      induced in a distinct time frame in that expression of most MMPs was induced
      during the early phase of liver injury, was maximal during the inflammatory
      reaction, and was diminished in the recovery phase. In contrast, TIMP and MMP-2
      steady state mRNA levels remained constant in the early phase, were strongly
      induced during tissue inflammation, and remained increased until the recovery
      phase. Interestingly, hepatic TNF-alpha expression paralleled the MMP induction
      profile, while the increase of TGF-beta1 expression mapped to the increase of
      TIMPs. Chronic liver injury was accompanied by an increase in the steady state
      mRNA levels of MMP-2 and TIMPs, while other MMPs remained more or less unchanged
      or were diminished. Partial hepatectomy was followed by a dramatic increase of
      MMP-14 and to a lesser extent also of TIMP-1 expression; other MMPs and TIMPs
      were not significantly induced. Liver injury is accompanied by profound changes
      in hepatic MMP/TIMP expression, the latter being critically dependent on the type
      of injury. Single toxic injury resulting in complete restoration was
      characterized by a sequential induction of MMPs and TIMPs suggesting initial
      matrix breakdown and matrix restoration thereafter. Chronic liver injury leading
      to fibrosis displays overall diminished matrix degradation mainly through TIMP
      induction, while liver regeneration induced by partial hepatectomy caused an
      induction of MMP-14 and TIMP-1 only, which might be unrelated to matrix turnover
      but connected to pericellular fibrinolysis or fibrolysis required for
      hepatocellular replication.

PMID- 10933222
TI  - Nuclear transport of histone 2b in mammalian cells is signal- and energy
      dependent and different from the importin alpha/beta-mediated process.
AB  - Histone 2b nuclear transport was investigated using the digitonin-permeabilized
      cell system and the rat liver resealed nuclear envelope system. In permeabilized
      cells, maximal uptake of histone 2b is dependent on cytosolic components and an
      appropriate energy source. Addition of the recombinant proteins importin
      alpha/beta, and Ran, as well as ATP and GTP, to cytosol-depleted permeabilized
      cells does not enhance the uptake of histone 2b in contrast to that of
      nucleoplasmin serving as a control. Nuclear import of histone 2b cannot be
      blocked by addition of an excess of a nuclear localization signal-bearing peptide
      or nucleoplasmin. Similar results were obtained with resealed nuclear envelopes.
      As shown previously, resealed vesicles respond to the importin signal for the
      uptake of nuclear localization signal-bearing proteins which allows investigation
      of the import mechanism independent of intranuclear binding to chromatin. Uptake
      of histone 2b therefore seems to be an energy-requiring transport mechanism
      different from the import of proteins bearing a typical nuclear localization
      signal.

PMID- 10933223
TI  - The organization of adherens junctions in mouse osteoblast-like cells (MC3T3-E1)
      and their modulation by triiodothyronine and 1,25-dihydroxyvitamin D3.
AB  - Cadherin-mediated cell-cell adhesion is essential for the development and
      survival of multicellular tissues. Thus it is hypothesized that these molecules
      also play a fundamental role for the development and maintenance of bone by
      mediating cellular crosstalk between osteogenic cells and by providing targets
      for the sorting and migration of osteogenic precursors toward the bone surface.
      We describe the localization of cadherin-11 and N-cadherin along the cell margins
      of mouse osteoblast-like cells, the colocalization of "pancadherin" with alpha
      catenin, beta-catenin, p120, and vinculin, and the association of these complexes
      with the actin microfilaments. Furthermore, we measured the influence of cell
      confluency and the effects of the osteogenic hormones triiodothyronine (T3) and
      1,25-dihydroxyvitamin D3 (D3) on these parameters. By mRNA studies we found the
      abundantly expressed cadherin-11 being unaffected during T3- and D3-induced
      osteoblastic differentiation. However, protein levels of N-cadherin and
      "pancadherin" were strongly suppressed by D3. We also observed a clear
      distinction in cadherin immunolocalization when comparing confluent control and
      confluent hormone-treated cultures. Immunoprecipitation experiments indicated
      that vinculin is part of the junctional complex, and that the association of
      "pancadherin"/beta-catenin is strongly increased after treatment with T3 which
      might influence the functional competence of cell-cell contacts. Thus, this study
      demonstrates the molecular organization of adherens junctions in mouse
      osteoblastic MC3T3-E1 cells and their sensitivity to the osteogenic factors T3
      and D3 in confluent cultures.

PMID- 10933224
TI  - Cytoskeletal involvement during hypo-osmotic swelling and volume regulation in
      cultured chick cardiac myocytes.
AB  - The membrane skeleton in spherical cardiac myocytes subjected to hypo-osmotic
      challenge was examined by laser scanning confocal microscopy. A distinct cortical
      layer intimately localized under the plasmalemma was revealed for spectrin and
      actin (including filamentous actin and alpha-sarcomeric actin). Desmin filaments
      were abundant and in close contact with the plasmalemma. During swelling and
      subsequent regulatory volume decrease (RVD) the structural integrity of these
      cytoskeletal elements remained intact, and the close association between actin
      and plasmalemma persisted as confirmed by double immunolabeling. Subplasmalemmal
      beta-tubulin labeling was sparse. Hypo-osmotic conditions disrupted the
      microtubules and depolymerized tubulin. Neither pretreatment with taxol nor with
      colchicine, resulted in any effect on cell volume regulation. The present results
      show that actin, desmin, and spectrin contribute to a subplasmalemmal
      cytoskeletal network in spherical cardiac myocytes, and that this membrane
      skeleton remains structurally intact during swelling and RVD. It is suggested
      that the integrity of this membrane skeleton is important for stabilization of
      the plasmalemma and the membrane-integrated proteins during hypo-osmotic
      challenge, and that it may participate in the regulation of the cell volume.

PMID- 10933225
TI  - Enzyme cytochemical localization of sarcosine oxidase activity in the liver and
      kidney of several mammals.
AB  - We investigated the enzyme cytochemical localization of sarcosine oxidase (SOX)
      in the liver and kidney of several mammals using a cerium technique. First we
      measured the enzyme activities in the liver and kidney of several mammals and in
      several organs of mice. The highest activity was found in the Chinese hamster,
      followed by the mouse. Therefore, we used hamster and mouse tissues for enzyme
      cytochemistry. The liver and kidneys were fixed by perfusion with various
      concentrations of glutaraldehyde for 10 min. Tissue slices were incubated in
      reaction medium consisting of 50 mM TRIS-maleate buffer (pH 7.8), 9 mM sodium
      azide, 9.8 mM sarcosine, 25 microM FAD, 2 mM cerium chloride, 0.002% saponin, and
      0.003% Triton X-100 for 0.5-8 h at 37 degrees C. Optimum staining reaction was
      obtained in tissues fixed with 0.2% glutaraldehyde, followed by incubation for 2
      4 h. Electron-dense reaction products were present exclusively in peroxisomes.
      Within the peroxisomes strong reactions were observed in the matrix subjacent to
      the limiting membrane decreasing toward the center. The staining reaction was
      completely inhibited by 2 mM N-bromosuccinimide. These results indicated that SOX
      is a peroxisomal enzyme and that the enzyme might be associated with the
      peroxisomal membrane.

PMID- 10933226
TI  - Paediatric neurosurgery, old art and new science.

PMID- 10933227
TI  - Medulloepithelioma of the optic nerve with intradural extension--report of two
      cases and a review of the literature.
AB  - Medulloepithelioma is an uncommon tumour. Among the various sites of origin the
      optic nerve is rare. We report here two cases of medulloepithelioma of the optic
      nerve that had extended intradurally into the cranial cavity. A review of the
      published cases is also given.

PMID- 10933228
TI  - Treatment of early-onset dystonia: update and a new perspective.
AB  - Dystonia is a rare disease of childhood, often leading to devastating functional
      impairment. Medical treatment is reviewed, although its efficacy is often
      limited. Recent advances in functional neurosurgery have opened up a new field in
      the management of dystonic patients, and the results of deep brain stimulation
      are given particular emphasis.

PMID- 10933229
TI  - Medulloblastoma in children--the Ottawa experience.
AB  - A retrospective review of 36 children diagnosed with medulloblastoma in the
      Ottawa area between 1974 and 1997 was completed (mean age 7.8+/-4.2 years, range
      1.2-15.3 years). Via a suboccipital approach, complete tumor resection was
      achieved in 75% and subtotal resection (>90%) in 25%, without any operative
      mortality. The tumor was located in the vermis in 39% and in the cerebellar
      hemisphere in 11%; it occupied both locations in 50%. In 47% of the children a
      ventriculoperitoneal shunt was required. Postoperatively, craniospinal radiation
      at 3600 cGy with a boost to the posterior fossa was administered. Chemotherapy
      was used in 56%. The 1-year survival rate was 92%, and survival plateaued at 54%
      at 5 years. Children less than 3 years of age fared worse than those over 3 years
      old. While the male-to-female ratio was 1.6:1, there was no gender difference in
      survival. Chang's classification was used to grade the tumors. T stage did not
      have an impact on survival, but M stage did. No statistically significant
      difference in survival was found between the patients who had a total resection
      and those who had a subtotal resection. There was no difference in survival in
      terms of tumor location, hydrocephalus or ventriculoperitoneal shunt.
      Chemotherapy showed no survival benefit. The recurrence rate was 26%, and its
      timing followed Collin's law. Recurrence led to death within 1-9 months. GH
      deficiency was diagnosed in 5 patients and hypothyroidism in 4 patients. The mean
      follow-up time was 4.4+/-3.7 years, with a range of 2.5 months to 16.5 years.
      Fourteen patients died, 5 were lost to follow-up, and 7 were transferred to adult
      care without persistent disease. Ten children are presently being followed up by
      the Neuro-oncology Clinic. Four children continue to be followed through
      psychology services. Our results are comparable to those in larger series, and
      are similar to those of the Montreal Children's Hospital.

PMID- 10933230
TI  - Proof of the patent subcutaneous fibrous tract in children with V-P shunt
      malfunction.
AB  - A connective tissue sheath that forms around the peritoneal catheter of silicone
      ventriculo-peritoneal (V-P) shunt tubing is quite often observed in children with
      V-P shunts. However, proof of the passage of cerebrospinal fluid (CSF) through
      these sheaths has been reported in only one published study to date. We present
      four cases associated with chronic malfunction of the V-P shunt peritoneal
      catheter. In these cases, CSF passage through the subcutaneous fibrous tract,
      which had a pericatheter connective tissue sheath, was demonstrated around the V
      P shunt peritoneal catheter. In the first case the patient suffered intermittent
      headache attacks over a long period of time; abdominal migration of the
      peritoneal catheter was detected. The second patient, who had been asymptomatic
      in the follow-up period with an outgrown peritoneal catheter, was admitted with
      acute hydrocephalus symptoms. A peritoneal catheter disconnection was detected in
      another patient, who had had multiple shunt revisions previously. In the last
      case, an obstruction of the peritoneal catheter was detected. The existence of
      the subcutaneous fibrous tract and its function were demonstrated by radio-opaque
      shuntogram in two cases and radionuclide shuntogram in the other two cases. In
      all four cases V-P shunt revision was performed. Within this study, the possible
      passage of CSF through a fibrous tract in cases of migration, outgrowth,
      disconnection or obstruction of the peritoneal shunt catheter was demonstrated.
      In conclusion, patients with shunt malfunction with a well-grown pericatheter
      fibrous sheath who are either asymptomatic or minimally symptomatic and show no
      evidence of active ventricular dilatation on their cranial CT scan should not be
      regarded as having arrested hydrocephalus until radio-opaque or radionuclide
      shuntogram studies have been done.

PMID- 10933231
TI  - Immunohistochemical tenascin-C expression in paediatric supratentorial
      glioblastoma multiforme.
AB  - Tenascin-C (TN-C) plays an important part in the growth of neoplastic tissue,
      leading to new vessel development. TN-C has been assessed in adult glioblastoma
      multiforme (GBM) and has been evaluated as anti-neoplastic therapy. No studies
      have focused on this tissue in paediatric GBM. Tissues were obtained from six
      paediatric supratentorial GBMs. Immunohistochemistry was performed using a mouse
      antibody directed against human TN-C, and expression in tumour vasculature was
      described on the basis of TN-C immunoreactivity. The expression was minimal in
      three, moderate in two, and intense in one specimen. TN-C was not correlated with
      clinical history, neurological findings, or with tumour site. Although based on a
      limited number of patients, this study provides additional insights into tumour
      growth modulation and cytogenetic profile of paediatric GBM. The detailed
      understanding of events responsible for GBM growth is a prerequisite for the
      development of therapeutic modalities leading to improved prognosis and cure.

PMID- 10933232
TI  - Recurrence in a different location of a cerebral arteriovenous malformation in a
      child after radiosurgery.
AB  - The case of a 9-year-old girl with a right parietal arteriovenous malformation
      (AVM) of the brain obliterated after gamma knife (GK) radiosurgery with
      subsequent regrowth in a different site is reported. As far as we know, this is
      the first reported case of regrowth of an AVM in a different location after
      radiosurgery in a child. This situation has to be considered within the context
      of causes of unsuccessful treatment of AVMs with radiosurgery and justifies
      angiographic monitoring of pediatric patients until they reach adulthood.

PMID- 10933233
TI  - Lateral spike conduction velocity in the visual cortex affects spatial range of
      synchronization and receptive field size without visual experience: a learning
      model with spiking neurons.
AB  - Classical receptive fields (cRF) increase in size from the retina to higher
      visual centers. The present work shows how temporal properties, in particular
      lateral spike velocity and spike input correlation, can affect cRF size and
      position without visual experience. We demonstrate how these properties are
      related to the spatial range of cortical synchronization if Hebbian learning
      dominates early development. For this, a largely reduced model of two successive
      levels of the visual cortex is developed (e.g., areas V1 and V2). It consists of
      retinotopic networks of spiking neurons with constant spike velocity in lateral
      connections. Feedforward connections between level 1 and 2 are additive and
      determine cRF size and shape, while lateral connections within level 1 are
      modulatory and affect the cortical range of synchronization. Input during
      development is mimicked by spike trains with spatially homogeneous properties and
      a confined temporal correlation width. During learning, the homogeneous lateral
      coupling shrinks to limited coupling structures defining synchronization and
      related association fields (AF). The size of level-1 synchronization fields
      determines the lateral coupling range of developing level-1-to-2 connections and,
      thus, the size of level-2 cRFs, even if the feedforward connections have distance
      independent delays. AFs and cRFs increase with spike velocity in the lateral
      network and temporal correlation width of the input. Our results suggest that AF
      size of V1 and cRF size of V2 neurons are confined during learning by the
      temporal width of input correlations and the spike velocity in lateral
      connections without the need of visual experience. During learning from visual
      experience, a similar influence of AF size on the cRF size may be operative at
      successive levels of processing, including other parts of the visual system.

PMID- 10933234
TI  - The dynamics of a neuronal culture of dissociated cortical neurons of neonatal
      rats.
AB  - Neuronal networks of dissociated cortical neurons from neonatal rats were
      cultured over a multielectrode dish with 64 active sites, which were used both
      for recording the electrical activity and for stimulation. After about 4 weeks of
      culture, a dense network of neurons had developed and their electrical activity
      was studied. When a brief voltage pulse was applied to one extracellular
      electrode, a clear electrical response was evoked over almost the entire network.
      When a strong voltage pulse was used, the response was composed of an early
      phase, terminating within 25 ms, and a late phase which could last several
      hundreds of milliseconds. Action potentials evoked during the early phase
      occurred with a precise timing with a small jitter and the electrical activity
      initiated by a localized stimulation diffused significantly over the network. In
      contrast, the late phase was characterized by the occurrence of clusters of
      electrical activity with significant spatio-temporal fluctuations. The late phase
      was suppressed by adding small amounts of D(-)-2-amino-5-phosphonovaleric acid to
      the extracellular medium, or by increasing the amount of extracellular Mg2+. The
      electrical activity of the network was substantially increased by the addition of
      bicuculline to the extracellular medium. The results presented here show that the
      neuronal network may exist in two different dynamical states: one state in which
      the neuronal network behaves as a non-chaotic deterministic system and another
      state where the system exhibits large spatio-temporal fluctuations,
      characteristic of stochastic or chaotic systems.

PMID- 10933235
TI  - A neural mechanism of hierarchical discrimination of odors in the olfactory
      cortex based on spatiotemporal encoding of odor information.
AB  - We propose a neural mechanism for discrimination of different complex odors in
      the olfactory cortex based on the dynamical encoding scheme. Both constituent
      molecules of the odor and their mixing ratios are encoded simultaneously into a
      spatiotemporal activity pattern (limit cycle attractor) in the olfactory bulb
      [Hoshino O, Kashimori Y, Kambara T (1998) Biol Cybern 79:109-120]. We present a
      functional model of the olfactory cortex consisting of some dynamical mapping
      modules. Each dynamical map is represented by itinerancy among the limit cycle
      attractors. When a temporal sequence of spatial activity patterns corresponding
      to a complex odor is injected from the bulb to the network of the olfactory
      cortex, the neural activity state of each mapping module is fixed to a relevant
      spatial pattern injected. Recognition of an odor is accomplished by a combination
      of firing patterns fixed in all the mapping modules. The stronger the response
      strength of the component, the earlier the component is recognized. The
      hierarchical discrimination of an odor is made by recognizing the components in
      order of decreasing response strengths.

PMID- 10933236
TI  - Short-window spectral analysis of cortical event-related potentials by adaptive
      multivariate autoregressive modeling: data preprocessing, model validation, and
      variability assessment.
AB  - In this article we consider the application of parametric spectral analysis to
      multichannel event-related potentials (ERPs) during cognitive experiments. We
      show that with proper data preprocessing, Adaptive MultiVariate AutoRegressive
      (AMVAR) modeling is an effective technique for dealing with nonstationary ERP
      time series. We propose a bootstrap procedure to assess the variability in the
      estimated spectral quantities. Finally, we apply AMVAR spectral analysis to a
      visuomotor integration task, revealing rapidly changing cortical dynamics during
      different stages of task processing.

PMID- 10933237
TI  - A dynamical-systems model for Parkinson's disease.
AB  - The juxtaposition of hypokinetic and hyperkinetic symptoms in Parkinson's disease
      (PD) presents a challenge in modeling the basal ganglia. We propose a model of
      the striatum that can account for the mixture of symptoms seen in PD. In the
      model, the problem of motor planning is cast in terms of a particle in a
      potential, where potentials are generated internally in striatal modules, subject
      to afferent control. Planned movement is governed by Hamilton's equations, where
      potential energy is supplied by potentials expressed in the striatum. To test the
      model in realistic situations, a dynamic simulation of a two-link robot arm was
      used. Normal movement is modeled and shown to exhibit observed experimental
      properties. Symptoms of PD are reproduced by modeling hypothetical consequences
      of PD pathology.

PMID- 10933238
TI  - Disparity tuning as simulated by a neural net.
AB  - Previous research has suggested that the processing of binocular disparity in
      complex cells may be described with an energy formalism. The energy formalism
      allows for a representation of disparity by differences in the position or in the
      phase of monocular receptive subfields of binocular cells, or by combination of
      these two types. We studied the coding of disparities with an approach
      complementary to previous algorithmic investigations. Since realization of these
      representations is probably not genetically determined but learned during
      ontogeny, we used backpropagation networks to study which of these three
      possibilities were realized within neural nets. Three types of networks were
      trained with noise patterns in analogy to the three types of energy models. The
      networks learned the task and generalized to untrained correlated noise pattern
      input. Outputs were broadly tuned to spatial frequency and did not respond to
      anti-correlated noise patterns. Although the energy model was not explicitly
      implemented, we could analyze the outputs of the networks using predictions of
      the energy formalism. After learning was completed, the model neurons preferred
      position shifts over phase shifts in representing disparity. We discuss the
      general meaning of these findings and the correspondences and deviations between
      the energy model, V1 neurons, and our networks.

PMID- 10933239
TI  - Identification of nonstationary dynamics in physiological recordings.
AB  - We present a novel framework for the analysis of time series from dynamical
      systems that alternate between different operating modes. The method
      simultaneously segments and identifies the dynamical modes by using predictive
      models. In extension to previous approaches, it allows an identification of
      smooth transition between successive modes. The method can be used for analysis,
      diagnosis, prediction, and control. In an application to EEG and respiratory data
      recorded from humans during afternoon naps, the obtained segmentations of the
      data agree with the sleep stage segmentation of a medical expert to a large
      extent. However, in contrast to the manual segmentation, our method does not
      require a priori knowledge about physiology. Moreover, it has a high temporal
      resolution and reveals previously unclassified details of the transitions. In
      particular, a parameter is found that is potentially helpful for vigilance
      monitoring. We expect that the method will generally be useful for the analysis
      of nonstationary dynamical systems, which are abundant in medicine, chemistry,
      biology and engineering.

PMID- 10933240
TI  - Hepatitis C virus infection in cocaine users--a silent epidemic.
AB  - Over a recent three year period, approximately 600 individuals responded to
      newspaper advertisements for research studies requiring healthy, cocaine using
      subjects. These subjects were screened using a standard phone interview in order
      to eliminate individuals with known medical or psychiatric illnesses that would
      exclude them from ongoing neuroimaging studies of drug abuse. Individuals were
      specifically asked about their hepatitis and HIV status. Of these, 170 subjects
      passed the phone screen, having no known medical or psychiatric illness outside
      of cocaine abuse/dependence and were willing to be further evaluated for the
      studies. These subjects were brought to the Medical College of Wisconsin's
      General Clinical Research Center and tested for, among other measures, hepatitis
      B, hepatitis C, and HIV. Of these, 144 completed the examination and all testing.
      In this cohort of assumed healthy subjects, 47 (33%) tested positive for
      antibodies to the hepatitis C virus (HCV). Only 7 (5%) tested positive for the
      hepatitis B surface antigen and 2 (1.4%) to HIV. The demographics of this cohort
      are 56% African-American, 81% male, 75% never-married, 55% unemployed with a mean
      age of 36 years. The percentage of subjects reporting any lifetime intravenous
      drug use among the HCV(+) and the HCV(-) cohorts was 77% vs. 29% respectively.
      Some routes of HCV transmission are still unclear and may reflect lifestyle or
      other factors related to cocaine use outside of parenteral drug use. Since almost
      all HCV infections become chronic, and many progress to chronic active hepatitis,
      cirrhosis, and ultimately hepatocellular carcinoma, these observations suggest a
      significant epidemic in an unsuspecting population with little regular access to
      health care. These individuals also form a large pool for the continued
      transmission of HCV to the general population. Additional public health
      interventions are suggested.

PMID- 10933241
TI  - Severely mentally ill patients with and without substance use disorders:
      characteristics associated with treatment attrition.
AB  - We aimed to describe characteristics associated with attrition for patients in
      community mental health treatment with chronic mental illness with and without
      substance use disorders. Baseline assessments included symptom severity,
      treatment satisfaction, social support, and a structured diagnostic interview.
      Treatment attrition was assessed at six months. At six months, 36% of the dual
      diagnosis group (n = 25), and 61% of the mental illness alone group (n = 23) were
      lost to follow-up. Attrition in the dually diagnosed group tended to be
      associated with less satisfaction with treatment, and higher mean symptom scores.
      There were no characteristics associated with attrition in the group of patients
      with mental illness alone. However, client satisfaction tended to increase among
      the mental illness alone patients that were successfully followed. The dually
      diagnosed group that remained in treatment had a significantly lower mean
      treatment satisfaction score than the mental illness alone group at six months.
      This type of investigation should aid in patient care and evaluation of treatment
      programs for persons with severe mental illness and co-occurring substance use
      disorders.

PMID- 10933242
TI  - Agency-based tracking of difficult-to-follow populations: runaway and homeless
      youth programs in St. Louis, Missouri.
AB  - OBJECTIVES: This study explored agency-based tracking methods for one of the most
      difficult-to-follow populations: runaway and homeless youth. METHODS: A total of
      118 program discharges from three federally funded agencies serving runaway/
      homeless youth in St. Louis, Missouri were tracked for a follow-up study of this
      population. Agency staff attempted to locate and interview program participants
      three months post-discharge using a protocol that systematically varied times and
      location of contact attempts. Separate analyses were conducted to compare the
      group of subjects whose locations were ascertained with those who were not, and
      who were successfully interviewed with those who were not. Variables related to
      the tracking protocol and individual descriptive and service use variables were
      examined in these analyses. RESULTS: Sixty-nine percent of the sample was
      successfully located and fifty-nine percent interviewed. Significant findings
      included: fewer contact attempts over fewer days were made for individuals
      successfully interviewed, individuals tracked through Division of Family Services
      were less likely to be both located and interviewed, and individuals successfully
      located were significantly younger. CONCLUSIONS: This report provides encouraging
      evidence that even relatively unsophisticated protocols for tracking agency
      clients developed in collaboration with community agencies can--with consistent
      implementation--yield follow-up samples that are acceptably representative of
      program participants.

PMID- 10933243
TI  - Expanded school mental health services: assessing needs related to school level
      and geography.
AB  - We surveyed 62 school administrators from three midatlantic (MD, VA, WV) and one
      northeastern (CT) state on factors relevant to developing school-based mental
      health programs. Administrators were from schools that varied on education level
      (elementary, middle, and high) and geographic location (urban, suburban, and
      rural), with equivalent numbers in each subgroup. Administrators provided ratings
      to questions grouped in five categories: (a) Stressful Conditions, (b)
      Internalizing Behavioral Problems, (c) Externalizing Behavioral Problems, (d)
      Substance Abuse, and (e) Barriers to Mental Health Care, and provided open-ended
      comments on needs of youth and mental health programs for them. They rated
      behavioral and substance abuse problems as progressively more serious as students
      advanced in school level. Urban youth were reported to encounter higher stress
      and present more severe internalizing problems than suburban or rural youth.
      Suburban and rural schools provided more health and mental health services than
      urban schools. Across geographic locales, physical health services far
      outnumbered mental health services. Findings related to barriers to mental health
      care, and the viability of schools as delivery sites for comprehensive mental
      health services, are discussed.

PMID- 10933245
TI  - The caregiver's perception of behavioral disturbance in relatives with
      schizophrenia: a stress-coping approach.
AB  - This article suggests some theoretical orientations in studying behavioral
      disturbance from a stress-coping perspective. First, an overview of Lazarus and
      Folkman's cognitive theory of stress is presented. Secondly, some linkages are
      proposed between the rating scales used to measure behavioral disturbance and the
      concepts of this theory. Future research directions are then suggested to further
      explore the affective, cognitive and behavioral responses related to the
      management of disturbing behaviors.

PMID- 10933244
TI  - Instruments measuring behavioral disturbance in relatives with schizophrenia.
AB  - This article presents a review of 16 instruments measuring behavioral disturbance
      of persons with schizophrenia as perceived by their family members. Information
      about the domain, the types of rating scales, and the psychometric properties of
      these instruments are provided. Future directions in the study of behavioral
      disturbance are proposed.

PMID- 10933246
TI  - Obsessive-compulsive disorder in popular magazines.
AB  - To examine what the general public is learning about Obsessive-Compulsive
      Disorder (OCD) through popular magazines, all articles listed in the Reader's
      Guide to Periodical Literature under the topic headings of "obsessive-compulsive
      behavior" or "obsessive-compulsive disorder" between 1983 and 1997 were read and
      rated. Only 31 of the 107 articles under these headings dealt explicitly with
      OCD, and these were found to be reasonably accurate in their presentations of
      symptoms, causes, and treatments. Many of the other articles under the target
      headings, however, focused on incidents of "stalking" of famous people by
      "obsessed" fans. The implications of the content patterns of these articles for
      understanding and misunderstanding of OCD are discussed.

PMID- 10933247
TI  - What recovery means to us: consumers' perspectives.
AB  - In this article two consumer leaders use their own experiences to explain the
      meaning and significance of recovery. They emphasize the importance of hope,
      personal responsibility, education, advocacy, and peer support. They also address
      controversial issues, such as the nature of the therapeutic relationship, the
      place of medications in symptom control, and the need for attitudinal changes in
      mental health professionals.

PMID- 10933249
TI  - The microbiological safety of food.

PMID- 10933248
TI  - Putting recovery into practice: a commentary on "what recovery means to us".

PMID- 10933250
TI  - Modulation of actA gene expression in Listeria monocytogenes by iron.
AB  - This study analysed the invasiveness of Listeria monocytogenes into enterocyte
      like Caco-2 cells in which iron depletion was achieved by picolinic acid
      treatment. Both entry and intracellular multiplication varied depending on the
      endogenous iron content of bacterial and eukaryotic cells. The behaviour within
      enterocytes was correlated with a 10-fold increased transcription of the actA
      gene observed in bacterial cells grown under conditions of iron stress.

PMID- 10933251
TI  - A putative heat-labile enterotoxin expressed by strains of Aeromonas media.
AB  - Fifteen isolates of Aeromonas media (seven from diarrhoeal stools, four from
      water and four from superficial skin ulcers of catfish) were examined for
      enterotoxin production. Ten of these isolates (six diarrhoeal, one from water and
      three from fish) caused accumulation of fluid in the initial rabbit ileal loop
      (RIL) tests. Isolates from diarrhoeal stools and fish caused relatively more
      fluid accumulation than those from water. Those strains that caused little or no
      fluid accumulation in the initial experiments became enterotoxin producers after
      one passage through RILs, regardless of source, and also showed gradual
      enhancement of fluid outpouring after each subsequent passage. Inocula of c. 1 x
      10(4) viable cells and 0.25 ml of culture filtrate (CF) caused fluid accumulation
      similar to that of toxigenic Vibrio cholerae 569B. The enterotoxic factor(s) were
      inactivated when held at 56 degrees C for 20 min or 65 degrees C for 10 min and
      showed biological activity over a wide range of pH values. These results suggest
      that strains of A. media, whether from diarrhoeal stools, water or infected fish,
      are potentially enterotoxigenic and may have the potential to produce a heat
      labile and pH-stable diarrhoeagenic factor in the same way as other known heat
      labile and pH-stable enterotoxins.

PMID- 10933252
TI  - Adhesion of Salmonella enterica var Enteritidis strains lacking fimbriae and
      flagella to rat ileal explants cultured at the air interface or submerged in
      tissue culture medium.
AB  - Rat ileal air interface and submerged explant models were developed and used to
      compare the adhesion of Salmonella enterica var Enteritidis wild-type strains
      with that of their isogenic single and multiple deletion mutants. The modified
      strains studied were defective for fimbriae, flagella, motility or chemotaxis and
      binding was assessed on tissues with and without an intact mucus layer. A
      multiple afimbriate/aflagellate (fim-/fla-) strain, a fimbriate but aflagellate
      (fla-) strain and a fimbriate/flagellate but non-motile (mot-) strain bound
      significantly less extensively to the explants than the corresponding wild-type
      strains. With the submerged explant model this difference was evident in tissues
      with or without a mucus layer, whereas in the air interface model it was observed
      only in tissues with an intact mucus layer. A smooth swimming chemotaxis
      defective (che-) strain and single or multiple afimbriate strains bound to
      explants as well as their corresponding wild-type strain. This suggests that
      under the present experimental conditions fimbriae were not essential for
      attachment of S. enterica var Enteritidis to rat ileal explants. However, the
      possession of active flagella did appear to be an important factor in enabling
      salmonellae to penetrate the gastrointestinal mucus layer and attach specifically
      to epithelial cells.

PMID- 10933253
TI  - Cytokine concentrations in seminal plasma from subfertile men are not indicative
      of the presence of Ureaplasma urealyticum or Mycoplasma hominis in the lower
      genital tract.
AB  - The inflammatory response to the presence of Ureaplasma urealyticum or Mycoplasma
      hominis in the lower genital tract of subfertile men without any signs or
      symptoms of infection was investigated by measuring the concentrations of
      interleukin (IL)-6, IL-8, tumour necrosis factor-alpha (TNF-alpha) and interferon
      gamma (IFN-gamma) in seminal plasma. Semen samples were collected from 30 culture
      positive subfertile males and 23 culture-negative subfertile males. Enzyme-linked
      immunosorbent assays showed that IL-8 was present in relatively high
      concentrations (0.12-4.8 ng/ml) in all semen samples investigated. In contrast,
      the other cytokines were only detectable in 72% (IFN-gamma), 44% (IL-6) and 19%
      (TNF-gamma) of the samples and were present in relatively low concentrations (1
      410 pg/ml). Seminal plasma cytokine concentrations were similar in samples from
      culture-positive and culture-negative males. These data strongly indicate that
      the presence of U. urealyticum or M. hominis in the lower genital tract of
      subfertile males reflects a silent colonisation rather than infection.

PMID- 10933254
TI  - Prolonged survival of mice with Pseudomonas aeruginosa-induced sepsis by rIL-12
      modulation of IL-10 and interferon-gamma.
AB  - Interleukin-12 (IL-12) is thought to play an important role as a modulator of
      levels of IL-10 and interferon-gamma (IFN-gamma). To address the therapeutic
      effects of rIL-12 in an endogenous sepsis model in mice, which closely mimics the
      pathophysiology of septicaemia in man, the effects of rIL-12 on the levels of
      cytokines such as IL-10 and IFN-gamma, and on the survival of septic mice
      infected with Pseudomonas aeruginosa PAO1 were examined. First, in the endogenous
      sepsis model, the serum levels of IFN-gamma and IL-10 remained normal until days
      8 and 10, respectively, when significant rises were seen. On day 11, levels of
      IFN-gamma returned to normal, but levels of IL-10 remained high. Interestingly,
      the IL-10 serum level reached a maximum 2 days later than the IFN-gamma serum
      level. In the light of these results, septic mice were given 0.01 microg of rIL
      12 by intraperitoneal injection and the serum levels of endogenous cytokines and
      the survival times were examined. Mice treated with rIL-12 on days 5, 6 and 7
      after infection survived significantly longer than control septic mice treated
      with saline only. Treatment with rIL-12 also led to a significant increase of the
      serum IFN-gamma level and a decrease of the serum IL-10 level on day 11. These
      results suggest that rIL-12 exerts therapeutic activity against endogenous sepsis
      caused by P. aeruginosa by stimulating proinflammatory responses and attenuating
      anti-inflammatory responses.

PMID- 10933255
TI  - Bactericidal effect of extracorporeal shock waves on Staphylococcus aureus.
AB  - Despite considerable knowledge about the effects of shock waves on eukaryotic
      soft tissues, no data are available concerning their effect on prokaryotic micro
      organisms. In vitro studies on the bactericidal effect of extracorporeal shock
      waves on staphylococci were performed with energy levels that are standard for
      the disintegration of calculi. Suspensions containing 10(4)-10(5) cfu of
      Staphylococcus aureus/ml were sealed in plastic tubes and exposed to shock waves,
      resulting in a mean decrease of 3.1 log(10). Whereas impulse rates of > or =350
      resulted in a decrease of cfu/ml equalling the detection limit, lower numbers of
      impulses did not result in an appreciable bactericidal effect. The bactericidal
      effect of extracorporeal shock waves might provide the basis for the development
      of novel therapeutic strategies for bacterial infections.

PMID- 10933256
TI  - Effect of probiotic bacteria on prevalence of yeasts in oropharyngeal biofilms on
      silicone rubber voice prostheses in vitro.
AB  - The proliferation of yeasts in the mixed bacterial and fungal biofilms colonising
      silicone rubber voice prostheses in laryngectomised patients is the main cause of
      malfunctioning of the valve mechanism on the oesophageal side of the prostheses.
      Indwelling voice prostheses usually have to be replaced every 3-4 months. The
      consumption of probiotic bacteria is largely motivated by health claims related
      to the urogenital and lower digestive tract, but not to the upper digestive
      tract. The present study examined the influence of probiotic bacteria on the
      prevalence of yeasts in oropharyngeal biofilms on silicone rubber voice
      prostheses, as formed in a modified Robbins device. Exposure of oropharyngeal
      biofilms on voice prostheses to suspensions of Bifidobacterium infantis 420 or
      Enterococcus faecium 603 did not significantly reduce the number of yeasts in the
      biofilm. However, suspensions of Lactobacillus fermentum B54, L. rhamnosus 744 or
      L. lactis cremoris SK11 led to a reduction in the number of yeasts harvested from
      the voice prostheses. Suspensions of L. casei Shirota and Streptococcus
      thermophilus B significantly reduced the number of yeasts in the biofilm to 39%
      and 33%, respectively. The reduction brought about in yeast prevalence in the
      mixed biofilm was greatest by exposure to a suspension of L. lactis 53, with
      yeast prevalence only 4% of the control. In conclusion, the study demonstrated
      that the prevalence of yeasts in oropharyngeal biofilms on silicone rubber voice
      prostheses might be controlled by consumption of probiotic bacteria.

PMID- 10933257
TI  - Effect of antimicrobial factors in human milk on rhinoviruses and milk-borne
      cytomegalovirus in vitro.
AB  - Various antimicrobial factors present in human milk were tested for in-vitro
      antiviral activity against three rhinoviruses (two clinical isolates and
      rhinovirus 2) and an isolate of cytomegalovirus (CMV) from human milk. These
      factors included the gangliosides GM1, 2 and 3, sialyl-lactose, chondroitin
      sulphates A, B and C, prostaglandins E2 and F2alpha, monolaurin, vitamin A and
      the protein lactoferrin. All were tested for their ability to inhibit growth of
      the viruses in cell culture. Human milk was also tested for antiviral activity
      against these viruses. Only vitamin A, monolaurin and lactoferrin inhibited the
      growth of CMV, whereas both prostaglandins enhanced the growth of this virus at
      least four-fold. CMV infects infants from milk but, nevertheless, the milk-borne
      CMV isolate showed no special resistance to any of the antiviral factors tested.
      None of the compounds inhibited or enhanced the growth of the rhinoviruses.
      However, human milk decreased the growth of some of the rhinoviruses and specific
      secretory immunoglobulin A (sIgA) neutralised the virus.

PMID- 10933258
TI  - Inhibition of virulence factor expression and swarming differentiation in Proteus
      mirabilis by p-nitrophenylglycerol.
AB  - Proteus mirabilis is a common cause of upper urinary tract infections that can
      involve invasion of host urothelial cells. The ability to invade urothelial cells
      is coupled closely to swarming, a form of multicellular behaviour in which
      vegetative bacteria differentiate into hyperflagellate, filamentous swarming
      cells capable of co-ordinated and rapid population migration. Co-ordinate
      expression of virulence factors including urease, protease, haemolysin and
      flagellin during swarm-cell differentiation in P. mirabilis has been reported. To
      investigate the effects of p-nitrophenylglycerol (PNPG), a potent anti-swarming
      agent, on the various swarming-associated traits of P. mirabilis and to elucidate
      the relationships among them, P. mirabilis growth rate, swarming/swimming
      activity, cell invasion ability and the ability to express various virulence
      factors were monitored in the presence or absence of PNPG. It was found that PNPG
      could inhibit the growth rate, swarming differentiation and swarming/swimming
      activities of P. mirabilis. The expression of virulence factors such as protease,
      urease, haemolysin and flagellin in P. mirabilis was also inhibited by PNPG. The
      ability of P. mirabilis to invade human urothelial cells was reduced dramatically
      in the presence of PNPG. These results suggest that PNPG has the potential to be
      developed as an agent active against the effects of P. mirabilis infection.

PMID- 10933259
TI  - A rapid method for detecting extracellular proteinase activity in Cryptococcus
      neoformans and a survey of 63 isolates.
AB  - A rapid method to detect extracellular proteolytic activity around colonies of
      Cryptococcus neoformans was developed with tannic acid used to complex with
      residual protein in a solid medium. A survey was conducted with 32 isolates of C.
      neoformans var. gattii and 31 isolates of C. neoformans var. neoformans which
      were cultured on medium containing gelatin as the sole nitrogen source. The
      annulus of clearing around fungal colonies was > 1.2 mm in 24 (77%) isolates of
      C. neoformans var. neoformans compared with only 7 (22%) isolates of C.
      neoformans var. gattii. There was no difference in proteolytic activity between
      environmental and human clinical isolates of C. neoformans. However, there was a
      difference between the size of the annulus around animal isolates of C.
      neoformans var. neoformans and isolates of the same variety from other sources.
      The annuli around the 14 animal isolates were all >1.2 mm, while 7 (70%) of 10
      human clinical isolates and only 3 (43%) of 7 environmental isolates were scored
      in the high proteinase range. A difference between the genetic types (as
      characterised by RAPD typing) of C. neoformans var. gattii was also evident with
      17 (77%) of 22 VG-I isolates having a small annulus compared with only 1 (17%) of
      6 VG-II and VG-III isolates with annuli of similar size. Relatively low
      proteinase production by C. neoformans var. gattii may reduce local and systemic
      spread of infection in mammalian hosts.

PMID- 10933260
TI  - Human epithelial cell death caused by Actinobacillus actinomycetemcomitans
      infection.
AB  - The gingival sulcus is the shallow crevice around the tooth, and its epithelium
      is a gateway for initial bacterial infection in periodontal disease. Recent
      studies have shown that Actinobacillus actinomycetemcomitans invades an
      epithelial cell line, KB cells, in vitro. The aim of the present study was to
      clarify the changes in KB cells after A. actinomycetemcomitans infection. The
      cytotoxic effects of A. actinomycetemcomitans on KB cells were determined at 72,
      96 and 120 h after infection by an MTT assay. Nuclear morphological changes were
      observed by staining with Hoechst 33258. Cytoplasmic histone-associated DNA
      fragmentation in the infected KB cells was determined by ELISA. A.
      actinomycetemcomitans was cytotoxic on KB cells, and condensation and degradation
      of the nuclei were observed. DNA fragmentation was increased after the infection.
      In addition, A. actinomycetemcomitans showed similar cytotoxic effects on human
      gingival epithelial cells. The present study demonstrated that A.
      actinomycetemcomitans induces apoptotic cell death of oral epithelial cells in an
      in-vitro culture system. This induced apoptosis might be involved in the
      initiation and progression of periodontitis.

PMID- 10933261
TI  - Evaluation of a phenotypic scheme for identification of the 'butyrate-producing'
      Peptostreptococcus species.
AB  - Gram-positive anaerobic cocci (GPAC) are isolated from approximately one quarter
      of all infections involving anaerobic bacteria. However, studies of the
      significance of this group of pathogens have been hindered by an inadequate
      taxonomy and the lack of a valid identification scheme. In the present study, a
      phenotypic scheme for the identification of 'butyrate-producing' GPAC based on
      the analysis of volatile fatty acid profiles by gas-liquid chromatography,
      biochemical profiles (including the use of the rapid ID 32 A commercial kit) and
      carbohydrate fermentation reactions, was evaluated. The identity of 68 clinical
      isolates of GPAC was determined by application of the scheme published by
      Murdoch. The scheme was found to be easy to apply and only four of the test
      isolates could not be readily assigned to a species or well-defined group. The
      species most frequently identified in the test collection were
      Peptostreptoccoccus vaginalis, P. tetradius and the betaGAL group. A large number
      of strains was assigned to the heterogeneous 'prevotii/tetradius' group. Some
      species regarded as being restricted to particular clinical sites were shown to
      be more widespread than previously thought. The clinical source of the isolates
      did not show any consistent correlation with species identity.

PMID- 10933262
TI  - Typing of Pneumocystis carinii f. sp. hominis by PCR-SSCP to indicate a high
      frequency of co-infections.
AB  - Broncho-alveolar lavage specimens from patients with Pneumocystis carinii
      pneumonia were investigated by PCR-single strand conformation polymorphism (SSCP)
      analysis of four genomic regions for P. carinii f. sp. hominis. In all, 32% of
      specimens produced two bands (one allele) for each of the four genomic regions,
      suggesting an infection with a single P.c. hominis type. The other specimens
      displayed more than two bands for at least one of the four genomic regions,
      suggesting several theoretical possibilities: co-infections, heterozygosity of
      diploid or polyploid organisms, or multicopy genes. Quantification of the
      different alleles and analysis of mixtures of specimens showed that different
      alleles of a genomic region were most often present in different proportions in a
      given specimen. In contrast, experiments with plasmid insertion of two alleles
      resulted in the detection of identical proportions of the two alleles. This
      suggests that neither heterozygosity of diploid organisms nor multicopy genes are
      responsible for the presence of two alleles. Unequal proportions are most likely
      explained by the occurrence of co-infections. The putative co-infecting types
      could be identified in the majority of specimens.

PMID- 10933263
TI  - Biochemical, antimicrobial susceptibility and genotyping studies on
      Corynebacterium urealyticum isolates from diverse sources.
AB  - Thirty-two isolates of Corynebacterium urealyticum, isolated between 1991 and
      1995, were studied by biochemical tests, phospholipid content, analysis of fatty
      and mycolic acids, ribotyping, whole-cell protein patterns and antimicrobial
      susceptibility to six antibiotics. Nineteen isolates were from human and human
      related sources (HHRS); the remainder were from animal and animal-related sources
      (AARS). Most C. urealyticum isolates were similar in their biochemical and whole
      cell protein profiles, although most HHRS isolates were alkaline phosphatase
      positive (84%) and produced almost identical protein patterns, whereas AARS
      isolates were quite diverse. The qualitative composition of cellular fatty acids
      was identical for all isolates examined. Twelve different ribotypes were obtained
      with HindIII producing four-to-seven bands. Ribotypes 8, 9 and 10 were
      predominant in isolates from HHRS, whereas in isolates from AARS, ribotypes 5 and
      6 predominated. AARS isolates were significantly less antibiotic-resistant, in
      comparison with HHRS isolates. Ribotyping appeared to be the most useful tool for
      strain characterisation.

PMID- 10933264
TI  - Isolation of Shiga toxin-producing Escherichia coli including O157:H7 strains
      from dairy cattle and beef samples marketed in Calcutta, India.

PMID- 10933265
TI  - Choosing a retrospective design to assess joint genetic and environmental
      contributions to risk.
AB  - The authors consider issues that should be weighed when designing a retrospective
      study in which a focus of interest is the joint role of genetic and environmental
      factors in causing a disease. In place of the classical case-control design, in
      which controls are sampled from the same population that gives rise to the cases,
      one could study cases only. The case-only approach can be usefully extended by
      genotyping the two biologic parents of each case and in effect letting the
      parental genotype data provide the genetic control. Alternatively, one could
      carry out a case-control study in which the controls are siblings or cousins of
      the cases and inference is based on within-family parameters. The authors compare
      and contrast the parameters that can be estimated and the assumptions that must
      be made when each of these designs is used. The investigator must also consider
      certain practical issues, such as the availability of parents or sibling
      controls.

PMID- 10933266
TI  - Risk factors for trachoma: 6-year follow-up of children aged 1 and 2 years.
AB  - The authors investigated the long-term stability of risk factors in predicting
      the presence of active trachoma and severe inflammatory trachoma in 176 children
      in Kongwa, Tanzania, who were aged 1 and 2 years in 1989 and were available for
      follow-up in 1995. Familial cattle ownership, living more than 2 hours away from
      a water source, and facial cleanliness at both time points were associated with
      the presence of active trachoma at both time points (odds ratio (OR) = 2.58, 95%
      confidence interval (CI): 1.15, 5.79; OR = 3.07, 95% CI: 1.23, 7.64; and OR =
      0.52, 95% CI: 0.26, 1.03, respectively). An association of familial cattle
      ownership with facial cleanliness and water accessibility was observed. Having a
      clean face at both time points was associated with lower odds of active trachoma
      at both time points for children in non-cattle-herding families (OR = 0.40, 95%
      CI: 0.18, 0.87). Living more than 2 hours away from a water source at both time
      points increased the odds of active trachoma at both time points in children of
      cattle-herding families (OR = 8.00, 95% CI: 1.99, 32.10). Noticeably, severe
      inflammatory trachoma at baseline predicted mortality in children from villages
      in which trachoma was less common (OR = 3.75, 95% CI: 1.09, 12.98). The results
      suggest that risk factor reduction could diminish persistent disease.

PMID- 10933268
TI  - Effect of continuing or stopping smoking during pregnancy on infant birth weight,
      crown-heel length, head circumference, ponderal index, and brain:body weight
      ratio.
AB  - The objective of this study was to determine whether stopping smoking between the
      first prenatal care visit and the 32nd week of pregnancy affects the smoking
      associated changes in five infant anthropometric indices. The study population
      consisted of 15,185 births in the Swedish Medical Birth Register from 1991 and
      1992. The associations between birth weight, crown-heel length, head
      circumference, ponderal index, brain:body weight ratio, maternal smoking status
      at the first prenatal care visit and at 32 weeks' gestation, and other maternal
      and infant characteristics were assessed using multivariate linear regression.
      The infants of 946 women who stopped smoking before week 32 of pregnancy were
      statistically indistinguishable from the 9,802 infants of nondaily smokers in
      terms of birth weight, head circumference, and brain:body weight ratio, but they
      retained a significant deficit in crown-heel length of 0.23 cm (standard error,
      0.08) and a significant elevation in ponderal index of 0.027 (standard error,
      0.009). In this study, stopping smoking between the first prenatal care visit and
      week 32 of pregnancy prevented smoking-associated deficits in infant birth
      weight, head circumference, and brain:body weight ratio, but did not completely
      prevent deficits in crown-heel length in comparison with nonsmokers' infants of
      the same age, and did not prevent elevation of ponderal index in comparison with
      nonsmokers' infants of the same weight and age.

PMID- 10933267
TI  - Inverse association of physical fitness with plasma fibrinogen level in children:
      the Columbia University BioMarkers Study.
AB  - Plasma fibrinogen has emerged as a risk factor for cardiovascular disease in
      adults, but relatively little is known about the correlates of plasma fibrinogen
      level in childhood. In the Columbia University BioMarkers Study (1994-1998), the
      authors evaluated the association between physical fitness and plasma fibrinogen
      level in 193 children 4-25 years old; 68% were Hispanic and 46% male. Fitness
      level assessed by treadmill testing was inversely associated with plasma
      fibrinogen (r = -0.24, p<0.001). Plasma fibrinogen levels showed a graded inverse
      relation with tertiles of fitness assessed by treadmill (p<0.001). In
      multivariate analyses, after adjustment for age, sex, race/ethnicity, body mass
      index, and presence of the A allele in the -455 position of the beta-fibrinogen
      promoter gene, the fitness level remained inversely associated with plasma
      fibrinogen level (beta = -1.3, 95% confidence interval (CI): -2.3, -0.34).
      Resting heart rate was also correlated with plasma fibrinogen level (r = 0.18,
      p<0.05). Fibrinogen levels (mg/dl) increased over tertiles of resting heart rate
      (p = 0.002) and were significantly associated with resting heart rate in
      multivariate analysis (beta = 0.82, 95% CI: 0.17, 1.5). These findings indicate
      that plasma fibrinogen is inversely associated with physical fitness in children
      independent of body mass index.

PMID- 10933269
TI  - Breast cancer and active and passive smoking: the role of the N-acetyltransferase
      2 genotype.
AB  - The association of breast cancer with passive and active smoking was investigated
      in slow and fast acetylators of aromatic amines in a Geneva, Switzerland, study
      in 1996-1997. A slow acetylator was homozygous for one, or heterozygous for two,
      of three N-acetyltransferase 2 (NAT2) polymorphisms determined on buccal cell DNA
      from 177 breast cancer cases and 170 age-matched, population controls. The
      reference group consisted of women never regularly exposed to active or passive
      smoke. Among premenopausal women, the odds ratios were homogeneous in slow and
      fast acetylators: 3.2 (95% confidence interval (CI): 1.2, 8.7) for passive
      smoking and 2.9 (95% CI: 1.1, 7.5) for active smoking. Among postmenopausal
      women, the odds ratios for fast acetylators were 11.6 (95% CI: 2.2, 62.2) for
      passive and 8.2 (95% CI: 1.4, 46.0) for active smoking; the corresponding effects
      were also apparent but less strong in slow acetylators. After the nonexposed and
      the passive smokers were grouped in a single reference category, active smoking
      was associated with postmenopausal breast cancer in slow acetylators (odds ratio
      (OR) = 2.5, 95% CI: 1.0, 6.2) but not in fast acetylators (OR = 1.3, 95% CI: 0.5,
      3.3). Thus, the associations of both passive and active smoking with breast
      cancer appear stronger in fast than in slow NAT2 genotypes. Separating passive
      smokers from the nonexposed impacts on the inference about a possible NAT2
      smoking interaction.

PMID- 10933270
TI  - Risk of ovarian cancer in relation to estrogen and progestin dose and use
      characteristics of oral contraceptives. SHARE Study Group. Steroid Hormones and
      Reproductions.
AB  - Although past studies have shown that oral contraceptives with 50 microg or more
      of estrogen reduce the risk of ovarian cancer, it is not clear whether newer,
      lower-dose formulations do as well. We conducted a population-based, case-control
      study in the Delaware Valley to assess the impact of dose of oral contraception
      on risk of ovarian cancer. Cases aged 20-69 years with a diagnosis of epithelial
      ovarian cancer ascertained between May 1994 and July 1999 (n = 767) were compared
      with community controls (n = 1,367). Compared with never users, the adjusted risk
      of ovarian cancer was reduced by 40% for oral contraceptive users overall, with
      longer duration of use affording greater protection. The ovarian cancer risk
      reduction was similar for women who initiated oral contraception before 1972,
      when high-dose pills dominated the market; between 1972 and 1980; and after 1980,
      when newer, lower-dose pills dominated. Oral contraceptive estrogen and progestin
      content were compared for cases and controls after adjustment for current age,
      number of pregnancies, race, and family history of ovarian cancer. Use of low
      estrogen/low-progestin pills afforded an estimated risk reduction (odds ratio =
      0.5, 95% confidence interval: 0.3, 0.6) that was identical to that for high
      estrogen/high-progestin pills (odds ratio = 0.5, 95% confidence interval: 0.3,
      0.7).

PMID- 10933271
TI  - Oral contraceptive and benign ovarian tumors.
AB  - Whether use of combined oral contraceptives (OC) protects against benign ovarian
      tumors is unknown. A case-control study of pathologically confirmed benign
      ovarian tumors was conducted in the New York City area and included cases
      diagnosed from January 1, 1992, to December 31, 1993, and controls identified by
      random digit dialing. There were 196 cases with serous adenomas, 176 with
      teratomas, 311 with endometriomas, and 65 with mucinous adenomas. Interview data
      were used to determine contraceptive use. Ever use of OC was associated with a
      decreased risk of these benign tumors (age- and hospital-adjusted odds ratio =
      0.79, 95% confidence interval: 0.60, 1.05). In histologic subgroup analyses, the
      risk of ovarian tumors was reduced for both current and past OC users. Among
      tumor subtypes, the risk reduction was greatest for women who had endometriotic
      lesions. The risk reduction also was greater for women who had used OC for more
      than 24 months. Protection against benign ovarian tumors may be an additional
      noncontraceptive benefit of OC use.

PMID- 10933272
TI  - Lifetime risks, incubation period, and serial interval of tuberculosis.
AB  - The lifetime risk of developing disease, the incubation period, and the time
      period between infection and transmission (the serial interval) are three
      important measures for interpreting trends in tuberculous infection and disease
      but are complicated by strong age dependencies regarding disease risk and by the
      potential for reinfection to occur. By using a model of the epidemiology of
      tuberculosis in England and Wales, the authors demonstrated that all three
      measures changed dramatically during the 20th century largely as a result of
      declines in the risk of infection. The estimated lifetime risk was highest
      following infection in early adulthood and declined with year of infection; the
      age-weighted average was approximately 12% during the last 50 years. Incubation
      period distributions depend on whether they are viewed prospectively (from
      infection to disease onset) or retrospectively (since infection for cases with
      disease onset at a particular time). As children rarely develop infectious forms
      of tuberculosis, infections acquired in childhood are associated with
      considerably longer serial intervals than those acquired in adulthood. These
      unusual properties are probably shared by other infections with long intervals
      between infection and disease. The results are important for interpreting data on
      transmission patterns, as are now being derived from molecular epidemiologic
      studies.

PMID- 10933273
TI  - Adiposity and mortality in men.
AB  - The relation between measures of adiposity and mortality has been a controversial
      topic. The authors examined prospectively the relation between several measures
      of adiposity and risks of overall and cause-specific mortality in 39,756 US men
      aged 40-75 years. During 10 years of follow-up (1986-1996), 1,972 deaths (747
      from cancer, 423 from cardiovascular disease, and 802 from other causes) were
      documented. An elevated risk of death among the leanest men was partly accounted
      for by excess mortality during early follow-up and high mortality among those
      with a history of recent weight loss. After exclusion of men with substantial
      recent weight loss and deaths occurring during the first 4 years of follow-up,
      overall and cardiovascular disease mortality among men aged <65 years increased
      linearly with greater body mass index (BMI) (weight (kg)/height (m)2);
      multivariate relative risks for overall mortality were 1.0 (referent) for a BMI
      of <23, 1.21 for a BMI of 23-24.9, 1.19 for a BMI of 25-26.9, 1.39 for a BMI of
      27-29.9, and 1.97 for a BMI of >30 (test for trend: p< 0.001). Among men aged >
      or =65 years, there were no significant relations between BMI and overall,
      cardiovascular disease, or cancer mortality risk. However, waist circumference
      strongly predicted risk of death from cardiovascular disease among the older men.
      These findings indicated that the relation between body fat and mortality was
      influenced by reverse causation and varied by age.

PMID- 10933274
TI  - Incidence of hypertension and educational attainment: the NHANES I epidemiologic
      followup study. First National Health and Nutrition Examination Survey.
AB  - Previous research has demonstrated the association between cardiovascular disease
      and education. However, few studies have described the incidence of hypertension,
      a risk factor for cardiovascular disease, by education or other socioeconomic
      status indicators. To examine the association between hypertension incidence and
      education, the authors analyzed data from the First National Health and Nutrition
      Examination Survey (NHANES I) Epidemiologic Followup Study (NHEFS) (1971-1984).
      The relative risk of hypertension incidence (blood pressure > or =160/95 and/or
      using antihypertensive medication) by education was calculated for non-Hispanic
      Whites (aged 25-64 years) and non-Hispanic Blacks (aged 25-44 years) normotensive
      at baseline using Cox proportional hazards models. The age-adjusted relative risk
      of hypertension incidence among persons with less than 12 years of education
      compared with those with more than 12 years was significant among non-Hispanic
      Whites aged 25-44 years (men: relative risk (RR) = 2.14, 95% confidence interval
      (CI): 1.29, 3.54; women: RR = 2.06, 95% CI: 1.39, 3.05) but not among non
      Hispanic Blacks (RR = 1.16, 95% CI: 0.63, 2.14). Relative risks for non-Hispanic
      White men remained stable after adjusting for age, systolic blood pressure, body
      mass index, and region of residence; relative risks for non-Hispanic White women
      were reduced but remained significant. Non-Hispanic White men and women aged 45
      64 years with less than 12 years of education were not at higher risk of
      developing hypertension compared with their more educated counterparts. These
      results demonstrate a significant interaction between age and education with an
      independent association between education and hypertension incidence among
      younger but not older non-Hispanic White men and women.

PMID- 10933275
TI  - Evaluation of alternative approaches to assign nutrient values to food groups in
      food frequency questionnaires.
AB  - Although every food frequency questionnaire (FFQ) requires a nutrient database to
      produce nutrient intake estimates, it is often unclear how a particular database
      has been generated. Moreover, alternative methods for constructing a database
      have not been rigorously evaluated. Using 24-hour recalls from the 1994-1996
      Continuing Survey of Food Intake by Individuals, the authors categorized 5,261
      individual foods reported by 10,019 adults into 170 food groups consistent with
      line items on an FFQ. These food groups were used to generate 10 potential
      nutrient databases for a FFQ that varied by whether the authors 1) used means or
      medians, 2) did or did not consider age, 3) incorporated collapsing strategies
      for small age-gender-portion size cells, 4) excluded outliers in a regression,
      and 5) used weighted median nutrient density x age-gender-portion size-specific
      median gram weights (Block method). Mean error, mean squared error, and mean
      absolute error were calculated and compared across methods, with error being the
      difference in total observed (from recalls for each individual) and total
      estimated intake (from each of the 10 methods) for seven nutrients. Mean methods
      for assigning nutrients to food groups were superior to median approaches for all
      measurements. Among the mean methods, no single variation was consistently
      better.

PMID- 10933276
TI  - Re: "Estimates of the annual number of clinically recognized pregnancies in the
      United States, 1981-1991".

PMID- 10933277
TI  - Re: "Use of two-segmented logistic regression to estimate change-points in
      epidemiologic studies".

PMID- 10933279
TI  - Battered gay men: an exploration of abuse, help seeking, and why they stay.
AB  - In comparison to a large body of literature about battered heterosexual women and
      a growing body about battered lesbians, this is one of the first published
      studies that investigates the experiences of battered gay and bisexual men.
      Results indicated that these men suffered patterns, forms, and frequencies of
      physical, emotional, and sexual abuse similar to what has been documented by
      research on battered heterosexual and lesbian women. Likewise, the most commonly
      reported reasons for staying--namely, hope for change and love for partner-
      appear to be universal to the experience of being battered. Unlike battered
      heterosexual women, respondents in this study were not likely to report that
      being financially trapped was a major reason why they had remained. HIV-status,
      however, appears to significantly influence their decision to remain. Moreover,
      lack of knowledge about domestic violence and the lack of availability of
      appropriate resources play a significant role in same-gender domestic violence
      victims' decisions to remain. Like battered lesbians, battered gay men
      infrequently sought assistance from battered women's services and perceived these
      services as not helpful. By contrast, individual counselors and agencies who
      provided individual counselors were rated as quite helpful.

PMID- 10933278
TI  - Re: "Does arsenic exposure increase the risk for circulatory disease?".

PMID- 10933280
TI  - Prevalence of extradyadic sex in male couples of mixed HIV status and its
      relationship to psychological distress and relationship quality.
AB  - This study assessed the prevalence of extradyadic sex and the relationship
      between such activity and psychological distress and relationship quality in male
      couples of mixed HIV serostatus. Sixty-three couples were interviewed and had
      sufficient data for inclusion in all analyses. With regard to sexual activity
      during the year prior to being interviewed, 19 (30%) couples were monogamous, 18
      (29%) described themselves as "open," 13 (21%) kept extradyadic sex a secret from
      their partners, and in 13 couples there was only partial knowledge of extradyadic
      sex. Though not statistically significant, monogamous and open couples
      consistently scored lower numerically on measures of psychological distress and
      higher on measures of relationship quality, compared to "partial knowledge" and
      "secretive" couples. When pooled, monogamous and open couples scored
      significantly higher on measures of dyadic consensus, affectional expression,
      dyadic satisfaction, and sexual satisfaction compared to the combined subgroup of
      partial knowledge and secretive couples.

PMID- 10933281
TI  - Gay male couples: the importance of coming out and being out to parents.
AB  - This exploratory study applied grounded theory methodology to examine what
      coupled gay men thought were the relationship impacts of being out to parents and
      in-laws. Data were collected from an accidental sample of 40 men in 20 homosexual
      couples using a standardized, open-ended interview. Virtually all of the
      respondents who had come out to their parents experienced initial and ongoing
      parental and in-law disapproval for their lifestyles and relationships. However,
      most men believed that it benefitted their unions to be out to their parents and
      partner's parents. Not having to hide the relationship was seen as a primary
      relationship advantage. Inclusion of one's partner in family events also emerged
      as a significant benefit. In contrast to the existing literature, a large
      proportion of respondents believed that parental/in-law antagonism had no adverse
      impacts on their dyads. They shielded their relationships by maintaining a strong
      sense of independence and in turn solid intergenerational boundaries. This study
      provides evidence to suggest that disclosure of sexual orientation to parents may
      be a distinctive, important developmental task for gay men which is critical to
      their relationships with their partners. Based on the findings of this research,
      mental health practitioners would be advised to assist gay men in the
      establishment and maintenance of strong intergenerational boundaries to protect
      their unions from parental/in-law disapproval.

PMID- 10933282
TI  - The value of children to lesbian and non-lesbian mothers.
AB  - This study compares the responses of a sample of lesbian and non-lesbian mothers
      to items on the Value of Children (VOC) Scale. This instrument measures the
      reasons that may explain why adults become parents and the values and functions
      for children in the lives of adults. Results indicate that there are more
      similarities than differences between lesbian and non-lesbian mothers in
      responses on the VOC Scale. Only one subscale that measures goals and incentives
      for assuming parenthood and having children differentiated between the groups.
      The lack of differences in response patterns on the VOC scale between lesbian and
      non-lesbian mothers may be attributed to the similar socialization experiences of
      women in our society regarding parenthood and the expectations of individuals
      upon assuming this role in adulthood. The significant differences in responses on
      the one subscale may be attributed to differences in world-views of lesbian and
      non-lesbian mothers.

PMID- 10933283
TI  - The effects of sexual orientation in the courtroom: a double standard.
AB  - Homonegativity is a term that many psychologists use to describe irrational fear
      of homosexuality. Due to a growing number of male rapes in the United States and
      the unchecked levels of homonegativity, it is hypothesized that homosexuals will
      be treated differently from heterosexuals in sexual assault trials. Four
      conditions were examined controlling for the gender and sexuality of both the
      defendant and the victim and a sexual assault trial text was created controlling
      for factors known to affect juror's decisions. Seventy-two participants were
      divided among the four conditions. This research supports the hypothesis with
      highly significant results. Future research is suggested.

PMID- 10933284
TI  - Attitudes of psychologists and psychologists-in-training to homosexual women and
      men: an Australian study.
AB  - Homophobic reactions of Australian psychologists (n = 43), postgraduate
      psychology students (n = 17) and undergraduate psychology students (n = 44) were
      compared using Van de Ven's (1994) measures of cognitive, affective and
      behavioral dimensions of homophobia. Results suggested that undergraduates were
      significantly more homophobic than psychologists in their thinking, intentional
      behavior and feelings of fear or discomfort in relation to lesbians and gay men.
      No other significant group differences were found. Gender differences were found
      only in relation to one affective dimension of homophobia. Low levels of positive
      affective response to homosexuals were observed across groups and gender. The
      study underscores the importance of assessing homophobic response
      multidimensionally. Implications for the training of Australian psychologists are
      discussed.

PMID- 10933285
TI  - Juan Gabriel and audience interpretation. cultural impressions of effeminacy and
      sexuality in Mexico.
AB  - Juan Gabriel's purported effeminacy and sexuality have made him a controversial
      subject in Mexico, but still loved by fans. Juan Gabriel, by trying to gain
      acceptance into Mexican society, has become part of a hybrid culture, between the
      feminine/masculine and homosexual/bisexual/heterosexual groups. This study
      focuses on interviews with 20 participants who discuss Juan Gabriel's popularity
      and sexuality. The findings of the study indicate that Juan Gabriel may be
      considered by his fans to be effeminate, and consequently homosexual. Even though
      homophobia is widespread in Mexico, Juan Gabriel's fans tend to ignore or
      exoticize his sexuality, thus affording his success. It is also possible that
      Juan Gabriel, consciously or not, uses his controversial sexuality as a way to
      generate popular interest.

PMID- 10933286
TI  - Routine vaginal cuff smear testing in post-hysterectomy patients with benign
      uterine conditions: when is it indicated?
AB  - BACKGROUND: By the age of 60 years, an estimated 33% of women will have undergone
      a hysterectomy. Approximately 85% of these hysterectomies are performed for
      benign disease. The object of this study was to evaluate cytologic findings from
      vaginal cuff smears in patients who have undergone hysterectomy for benign
      uterine conditions. METHODS: We conducted a community-based retrospective study
      and follow-up of women with vaginal cuff cytologic smears who had had a
      hysterectomy for benign uterine conditions. A total of 220 women were randomly
      selected who had one or more vaginal cuff smears. The main outcomes measures were
      invasive carcinoma, dysplastic lesions, and infections detected by vaginal cuff
      smear testing. The setting was a large inner-city hospital. RESULTS: Ninety-seven
      percent of 220 women who underwent hysterectomy for benign uterine conditions and
      who were observed for an average of 89 months had no cytologic abnormalities on
      vaginal cuff smears. Cytologic evaluation found no invasive carcinomas.
      Dysplastic lesions were detected in 7 patients (3%). Seventy percent of patients
      (n = 154) had one or more infections; these infections included bacterial
      vaginosis (106), trichomoniasis (95), candidiasis (40), koilocytosis suggestive
      of human papilloma virus (HPV) infection (3), and cytopathic effect of herpes
      (4). The prevalence of koilocytosis was much higher in the patients with
      dysplasia (P = .0003). CONCLUSIONS: Most routine vaginal cuff cytology screening
      tests need not be performed in women who have had a hysterectomy for benign
      uterine conditions.

PMID- 10933288
TI  - Colorado family practice graduates' preparation for and practice of emergency
      medicine.
AB  - BACKGROUND: Family physicians provide care in emergency departments, especially
      in rural areas; however, no published data describe how they perceive their
      preparation for emergency practice. We surveyed graduates of Colorado family
      practice residencies concerning their emergency medicine practice, their comfort
      working in emergency departments, and their perceived preparation for practicing
      emergency medicine. METHODS: Seventy recent graduates of Colorado residencies
      were surveyed regarding their location, work in emergency departments, contact
      with emergency medical services (EMS) personnel, and perceptions about their
      emergency medical training. RESULTS: Forty-five percent of respondents practiced
      in rural settings, 33% worked in emergency departments (56% rural, 14% urban),
      60% reported contact with EMS personnel (91% rural, 32% urban), 54% believed
      their training adequately prepared them for working in emergency departments (82%
      rural vs 32% urban), 63% of rural and 22% of urban respondents indicated they
      wanted more major trauma experience during training, 70% reported discomfort with
      managing trauma, and 44% were interested in a 6-month emergency medicine
      fellowship. CONCLUSIONS: Most respondents believed their training in emergency
      medicine was adequate; however, most also reported discomfort with trauma
      management. Improved training for family physicians who provide emergency care
      could include expanded trauma care opportunities, increased work with EMS
      personnel, and postresidency training.

PMID- 10933287
TI  - Low national breast and cervical cancer-screening rates in American Indian and
      Alaska Native women with diabetes.
AB  - BACKGROUND: The cervical cancer mortality rate for American Indian and Alaska
      Native women is twice that of all races in the United States. To date the only
      published national breast and cervical cancer-screening rates for American Indian
      and Alaska Native women are based on self-reported data. When the Indian Health
      Service (IHS) conducts an annual audit on patients with diabetes, it includes
      cancer screening. This observational study presents national breast and cervical
      cancer-screening rates for American Indian and Alaska Native women with diabetes.
      METHODS: Cancer-screening rates were extracted from the 1995 diabetic audit for
      the 12 IHS areas. These rates were compared with rates for women without diabetes
      of the same age, 50 to 69 years, by chart review, at four IHS hospitals in the
      Aberdeen IHS area. RESULTS: Screening rates for women with diabetes in the 12
      areas varied: mammogram (ever) 35% to 78%; clinical breast examination (last
      year) 28% to 70%, and Papanicolaou smear (last year) 26% to 69%. The Aberdeen IHS
      area women with diabetes had 51% more clinic visits per year than women without
      diabetes, but the groups had similar screening rates. CONCLUSION: Cancer
      screening rates for American Indian and Alaska Native women vary by region. In
      the Aberdeen IHS area, women with diabetes had more visits (missed opportunities)
      but similar screening rates as women without diabetes. The diabetic audit could
      be used to monitor national IHS cancer-screening trends for women with diabetes
      and in the Aberdeen IHS area for all women aged 50 to 69 years.

PMID- 10933289
TI  - Social anxiety disorder: common, disabling, and treatable.
AB  - BACKGROUND: Social anxiety disorder (also known as social phobia) is
      characterized by extreme fear, avoidance, or both of one or more social or
      performance situations, such as making a presentation, meeting new people, or
      eating in front of others. This condition is common, with a lifetime prevalence
      of up to 13%, and one third of affected persons have major dysfunction. METHODS:
      The English-language literature on social anxiety disorder indexed on MEDLINE was
      searched using the phrases "social phobia" or "social anxiety disorder;" this
      search was supplemented with other data sources, such as recent textbooks, to
      determine common clinical symptoms, differential diagnosis, and management in the
      primary care setting. RESULTS: Recognition and treatment of social anxiety
      disorder is poor; only a small minority of patients with this condition have it
      appropriately diagnosed or treated. Primary care physicians should suspect social
      anxiety disorder in patients who have specific symptoms and signs (such as
      hyperhidrosis, flushing, tremor, and white-coat hypertension), in patients who
      have symptoms of anxiety (such as chest pain, palpitations, or dizziness), or in
      patients who have another known anxiety disorder, depression, or substance abuse.
      Drug treatment consists of serotonin-reuptake inhibitors, monoamine oxidase
      inhibitors, or high-potency benzodiazepines. A specific type of psychotherapy
      called cognitive behavioral therapy is another effective treatment, but it is not
      acceptable or accessible to most patients. CONCLUSIONS: Because social anxiety
      disorder is common, disabling, and treatable, primary care physicians should
      intensify their efforts to recognize it.

PMID- 10933290
TI  - Medical evaluation for driver qualification for patients with cardiovascular
      disorders.
AB  - BACKGROUND: Primary care physicians commonly care for patients whose disabilities
      caused by cardiovascular diseases result in difficulty driving an automobile.
      Patients often seek their physician's advice as to whether they can continue to
      drive safely. METHODS: A MEDLINE literature search was performed from 1966 to
      2000, using the query terms "automobile driving" and "automobile driving and
      cardiac." Selected articles were reviewed, as well as additional articles found
      through review of the references. In some cases articles were found by searching
      the Internet using the above key words and new query terms guided by the results
      of the original search. RESULTS AND CONCLUSIONS: The most important factor
      determining eligibility is whether the patient reports manifestations of cerebral
      hypoxia. Laboratory procedures are available for patients in whom the decision is
      difficult. Sometimes a referral to a specialist is needed. Many patients with a
      known cardiovascular disorder can continue to drive safely. Some conditions
      require a waiting period before driving can be resumed, while others call for a
      complete cessation of driving. Several guidelines from the literature are listed
      that can be helpful to primary care physicians when dealing with questions from
      their patients on this important topic.

PMID- 10933291
TI  - Onychomycosis: improved cure rates with itraconazole and terbinafine.
AB  - Onychomycosis is a disease that is important to our patients. Based on the
      current literature, recent developments of newer antifungal agents have improved
      cure rates of onychomycosis in the past few years (Table 3). No significant
      differences in safety and tolerability between itraconazole and terbinafine
      exist. Terbinafine does appear to have a preferable drug interaction profile.
      Daily therapy with either agent at standard doses has been shown to be effective
      when compared with placebo. When studies have directly compared daily
      administration of terbinafine and itraconazole, both medications have shown
      similar efficacy. Daily terbinafine therapy, however, appears to be more
      effective than pulse therapy with itraconazole. In addition, one small study
      showed a trend in favor of continuous rather than intermittent terbinafine
      therapy and similar efficacy of intermittent itraconazole and intermittent
      terbinafine therapy. Furthermore, terbinafine is more cost-effective than
      itraconazole. Finally, as quality-of-life data suggest, onychomycosis is
      important to our patients and affects both physical and psychosocial components
      of our patients' lives.

PMID- 10933293
TI  - Small-bowel obstruction secondary to dental impression material.

PMID- 10933292
TI  - Treatment of AIDS and HIV-related conditions: 2000.

PMID- 10933294
TI  - Fatal massive amphetamine ingestion associated with hyperpyrexia.

PMID- 10933295
TI  - An unsuspected case of a degenerating leiomyoma.

PMID- 10933296
TI  - Hard subcutaneous lumps--pilomatricomas: a report of three cases.

PMID- 10933297
TI  - Can the generalist survive the 21st century?

PMID- 10933298
TI  - Diagnosis of bacterial sinusitis.

PMID- 10933299
TI  - Uterine inversion.

PMID- 10933300
TI  - Birth and death: through a child's eyes.

PMID- 10933301
TI  - Management of nondeflating urethral catheter.

PMID- 10933302
TI  - Toxic hepatitis caused by herbal medicine.

PMID- 10933303
TI  - Fibrinogen, other putative markers of inflammation, and weight gain in middle
      aged adults--the ARIC study. Atherosclerosis Risk in Communities.
AB  - PURPOSE: Weight gain is an important risk factor for the development of the
      metabolic syndrome, and inflammatory mediators are strongly associated with this
      syndrome. Our aim was to investigate whether inflammation predicts the
      development of weight gain in populations. RESEARCH METHODS AND PROCEDURES: We
      investigated selected markers of inflammation in the prediction of weight gain
      over an approximately 3-year period in a biethnic cohort of 13,017 men and women,
      45 to 64 years of age, using multiple linear and logistic regression modeling.
      RESULTS: In adjusted models, those in the highest quartile of fibrinogen gained,
      during the first 3 years of follow-up, an estimated 0.23 kg/year more than those
      in the lowest quartile (p < 0.001). Adjusted odds of a large (greater than the
      90th percentile) weight gain for those in the highest quartile of fibrinogen were
      1.65 (95% confidence interval [CI], 1.38 to 1.97) times those in the lowest
      quartile. Similarly adjusted odds ratios for a large weight gain for those with
      high levels of white blood cell count, factor VIII, and von Willebrand factor
      were 1.38 (1.14 to 1.67), 1.28 (1.08 to 1.53), and 1.28 (1.08 to 1.51),
      respectively. DISCUSSION: Fibrinogen and other putative markers of inflammation
      predict weight gain in middle-aged adults. Given the known links between the
      inflammatory response and intermediary metabolism and the methodological
      strengths of the Atherosclerosis Risk in Communities (ARIC) cohort, these
      findings, though without immediate clinical applicability, suggest that
      inflammatory processes play a role in the development of the metabolic syndrome
      and cardiovascular disease in part through stimulation of weight gain.

PMID- 10933304
TI  - Visceral adipose tissue and markers of the insulin resistance syndrome in obese
      black and white teenagers.
AB  - OBJECTIVE: To determine the relationships between visceral and general adiposity,
      cardiovascular fitness, and markers of the insulin resistance syndrome in obese
      black and white teenagers. RESEARCH METHODS AND PROCEDURES: Cross-sectional
      survey of 81 obese 13- to 16-year-old youths. Visceral adipose tissue was
      measured with magnetic resonance imaging, and percentage body fat was measured
      with dual-energy X-ray absorptiometry. Cardiovascular fitness was assessed with a
      submaximal treadmill test. Fasting blood samples were analyzed for
      lipids/lipoproteins and insulin. Resting blood pressure was obtained using an
      automated cuff. RESULTS: Visceral adipose tissue was significantly correlated
      with unfavorable levels of: triacylglycerol (r = 0.27, p < 0.05), total
      cholesterol (r = 0.27, p < 0.05), high-density lipoprotein cholesterol (r = 
      0.26, p < 0.05), the ratio of total cholesterol/high-density lipoprotein
      cholesterol (r = 0.42, p < 0.01), low-density lipoprotein cholesterol (r = 0.27,
      p < 0.05), apolipoprotein B (r = 0.38, p < 0.01), and systolic blood pressure (r
      = 0.30, p < 0.01). Multiple regression analyses revealed that visceral adipose
      tissue was more powerful than percentage body fat for explaining variance in
      lipoproteins (e.g., for the ratio of total cholesterol/high-density lipoprotein
      cholesterol, r2 = 0.13, p < 0.01, and for systolic blood pressure, r2 = 0.07, p <
      0.05). Ethnicity was the most powerful of the demographic predictors for blood
      lipids (r2 = 0.15 for triacylglycerol with lower levels in blacks; r2 = 0.10 for
      high-density lipoprotein cholesterol with higher levels in blacks; r2 = 0.06 for
      the ratio of total cholesterol/high-density lipoprotein cholesterol with lower
      levels in blacks). Cardiovascular fitness was not retained as a significant
      predictor of markers of the insulin resistance syndrome. DISCUSSION: Some of the
      deleterious relationships between visceral adiposity and markers for the insulin
      resistance syndrome seen in adults were already present in these obese young
      people.

PMID- 10933305
TI  - Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood
      Institute Family Heart Study.
AB  - OBJECTIVE: Considering that waist-to-hip ratio (WHR) is a simple anthropometric
      measure of obesity and is a better predictor of coronary heart disease than body
      mass index (BMI), the genetic underpinnings of WHR are of interest. The
      inheritance pattern of WHR, before and after adjustment for BMI (WHR-BMI), was
      investigated in 2713 individuals from 1038 nuclear families in the National
      Heart, Lung, and Blood Institute Family Heart Study (NHLBI-FHS). RESEARCH METHODS
      AND PROCEDURES: Waist and hip measurements were taken twice, and the means of the
      measurements were used to calculate the WHR. Adjustments for age were carried out
      separately by sex, using stepwise multiple regression procedures for WHR and WHR
      BMI phenotypes. Segregation analysis was applied using the unified model as
      implemented in the computer program POINTER. RESULTS: For age-adjusted WHR, the
      segregation results suggested an additive major gene that accounts for 35% of the
      phenotypic variance, and approximately 30% of the sample are homozygous for the
      "high" genotype. The results for age- and BMI-adjusted WHR were also compatible
      with a major gene; however, the multifactorial model provided the most
      parsimonious fit to the data. DISCUSSION: Although the genetic mechanisms for
      several obesity traits have been studied, tests of Mendelian segregation on this
      simple anthropometric measure (WHR) have not been reported previously. This study
      provides evidence for the presence of a major gene for age-adjusted WHR,
      suggesting that it is an appropriate trait for further genetic analysis,
      especially because it has strong predictive value and probably relates
      biologically to cardiovascular risk.

PMID- 10933306
TI  - Comparison of zinc reduction with platinum reduction for analysis of deuterium
      enriched water samples for the doubly labeled water technique.
AB  - OBJECTIVE: Isotope ratio mass spectrometry of hydrogen and oxygen is frequently
      used to determine total energy expenditure (TEE) using doubly labeled water.
      Conventionally, hydrogen isotope ratio is determined in hydrogen gas generated
      from water samples using zinc reduction. We compare this with a new automated
      platinum method to determine the ratios of hydrogen isotopes in deuterium
      enriched water samples. RESEARCH METHODS AND PROCEDURES: The platinum method of
      sample preparation was compared with the zinc method in three ways: analytical
      variation in deuterium enrichment (within sample; n = 51), analytical variation
      in TEE estimates (within sample set; n = 10), and level of agreement of TEE
      estimates between both methods (n = 14). RESULTS: For the zinc method, the
      standard deviation for multiple sets of triplicate 2H2O sample analysis was +/
      4.36 per thousand and +/-2.07 per thousand for platinum. The correlation between
      TEE estimates when sample sets were analyzed in duplicate was r = 0.89 for zinc
      and r = 0.83 for platinum. The intercept and slope of the regression line were
      significantly different from the line of identity for duplicate TEE estimates by
      zinc but were not different from the line of identity for platinum. After
      correction for the intra-assay variation of each method, the correlation between
      zinc and platinum for TEE was 0.77, and the intercept, but not the slope, of the
      regression was significantly different from the line of identity. The mean
      difference between the zinc method and the platinum method was 56 kcal/day, and
      the 95% confidence interval was -438 to 550 kcal/day. DISCUSSION: These data
      suggest that the platinum method is at least as reliable as the zinc method as a
      sample preparation technique for isotope ratio mass spectrometry of deuterium
      enriched water samples. The platinum method is also less costly and less labor
      intensive than the zinc method.

PMID- 10933307
TI  - The "good enough" body size as judged by people of varying age and weight.
AB  - OBJECTIVE: To examine the concept of the "good enough" body size acceptability
      across a wide range of ages and weight status. RESEARCH METHODS AND PROCEDURES:
      Subjects were 303 children, 427 adolescents, 261 young adults, and 326 middle-age
      adults who selected acceptable body sizes from an array of drawings representing
      their own age and gender. They also selected body sizes representing their own
      actual and ideal size. RESULTS: A large majority (87%) of subjects considered
      their own body size socially acceptable. This finding applied to both genders in
      all age groups and to underweight, normal weight, and overweight subjects. Even
      among obese subjects, 48% considered their own body size socially acceptable. For
      the large percentage of subjects who reported a discrepancy between their actual
      and ideal body sizes, most considered their own body size acceptable. This
      finding also applied to both genders in all age groups and to underweight, normal
      weight, and overweight subjects. DISCUSSION: Most male and female subjects across
      a wide range of ages and status considered their own body size to be within the
      range of socially acceptable body sizes even though, for many, it did not match
      their ideal. The implications of expanding body size research to include the
      conceptual framework of body size acceptability is discussed in terms of
      contributing to a paradigm of positive psychology.

PMID- 10933308
TI  - Central exendin-4 infusion reduces body weight without altering plasma leptin in
      (fa/fa) Zucker rats.
AB  - OBJECTIVE: To investigate whether chronic administration of the long-acting
      glucagon-like peptide-1 receptor agonist exendin-4 can elicit sustained
      reductions in food intake and body weight and whether its actions require an
      intact leptin system. RESEARCH METHODS AND PROCEDURES: Male lean and obese Zucker
      (fa/fa) rats were infused intracerebroventricularly with exendin-4 using osmotic
      minipumps for 8 days. RESULTS: Exendin-4 reduced body weight in both lean and
      obese Zucker rats, maximum suppression being reached on Day 5 in obese (8%) and
      Day 7 in lean (16%) rats. However, epididymal white adipose tissue weight was not
      reduced, and only in lean rats was there a reduction in plasma leptin
      concentration. Food intake was maximally suppressed (by 81%) on Day 3 in obese
      rats but was reduced by only 18% on Day 8. Similarly, in lean rats food intake
      was maximally reduced (by 93%) on Day 4 of treatment and by 45% on Day 8. Brown
      adipose tissue temperature was reduced from Days 2 to 4. Plasma corticosterone
      was elevated by 76% in lean but by only 28% in obese rats. DISCUSSION: Chronic
      exendin-4 treatment reduced body weight in both obese and lean Zucker rats by
      reducing food intake: metabolic rate was apparently suppressed. These effects did
      not require an intact leptin system. Neither does the absence of an intact leptin
      system sensitize animals to exendin-4. Partial tolerance to the anorectic effect
      of exendin-4 in lean rats may have been due to elevated plasma corticosterone and
      depressed plasma leptin levels, but other counter-regulatory mechanisms seem to
      play a role in obese Zucker rats.

PMID- 10933309
TI  - The effect of repeated episodes of dietary restriction and refeeding on systolic
      blood pressure and food intake in exercise-trained normotensive rats.
AB  - OBJECTIVE: To explore the effects of weight cycling and exercise on blood
      pressure and macronutrient intake in Sprague-Dawley rats. RESEARCH METHODS AND
      PROCEDURES: Female Sprague-Dawley rats (n = 62; 5 months old) were assigned to an
      ad libitum (Con) or weight-cycled (Cyc) group. They were either sedentary (Con
      Sed and Cyc-Sed) or exercise-trained (Con-Ex and Cyc-Ex) on a motorized treadmill
      (20 m/minute; 60 minutes/day; 6 days/week). The Cyc groups underwent 2 cycles of
      3 weeks of 60% food restriction followed by 5 weeks of ad libitum refeeding using
      a macronutrient self-selection diet. Body mass and food intake were analyzed
      weekly. Systolic blood pressure (SBP) was measured at baseline and during the
      first and fifth weeks of each refeeding. RESULTS: For both cycling periods, SBP
      was elevated in Cyc vs. Con groups at Week 1 of refeeding, but was similar among
      groups by Week 5 of refeeding. Both Con groups had greater total energy intake
      than the Cyc groups for both cycling periods (Cycle 1: 2882.2 +/- 75.1, Con-Sed;
      2916.1 +/- 67.1, Con-Ex; 2692.2 +/- 58.7, Cyc-Sed; and 2780.5 +/- 52.4 kcal, Cyc
      Ex) (Cycle 2: 2815.8 +/- 75.1, Con-Sed; 2938.8 +/- 49.4, Con-Ex; 2577.1 +/- 60.5,
      Cyc-Sed; and 2643.5 +/- 65.9 kcal, Cyc-Ex). Relative fat intake (percentage of
      total kcal/week) was significantly less for Con-Ex and Cyc-Ex than Con-Sed and
      Cyc-Sed throughout both refeeding periods. DISCUSSION: Weight cycling failed to
      produce significant sustained effects on SBP, body mass, or food intake. Exercise
      training, irrespective of diet, lowered dietary fat intake.

PMID- 10933310
TI  - Increased adipose angiotensinogen gene expression in human obesity.
AB  - OBJECTIVE: Adipose angiotensinogen has been suggested as a stimulator of adipose
      tissue growth and development. Therefore, the association of subcutaneous adipose
      angiotensinogen gene expression with human obesity was studied. RESEARCH METHODS
      AND PROCEDURES: The study group consisted of 17 men, undergoing either gastric
      banding for obesity or elective laparoscopic cholecystectomy (7 obese, 10 non
      obese men; body mass index 22 to 51 kg/m2; age 26 to 68 years). Subcutaneous
      adipose angiotensinogen mRNA and 18S ribosomal RNA (reference gene) levels were
      measured using competitive quantitative reverse transcriptase-polymerase chain
      reaction. RESULTS: Adipose angiotensinogen mRNA expression was about two times
      increased in obesity. The levels of 18S rRNA did not differ between the two
      groups. Body weight correlated independently and positively with adipose
      angiotensinogen mRNA expression after adjusting for differences in age and
      height. DISCUSSION: Adipose angiotensinogen gene expression is elevated in
      obesity in men.

PMID- 10933311
TI  - The obesity epidemic: metabolic imprinting on genetically susceptible neural
      circuits.
AB  - The apparent obesity epidemic in the industrialized world is not explained
      completely by increased food intake or decreased energy expenditure. Once obesity
      develops in genetically predisposed individuals, their obese body weight is
      avidly defended against chronic caloric restriction. In animals genetically
      predisposed toward obesity, there are multiple abnormalities of neural function
      that prime them to become obese when dietary caloric density and quantity are
      raised. Once obesity is fully developed, these abnormalities largely disappear.
      This suggests that obesity might be the normal state for such individuals.
      Formation of new neural circuits involved in energy homeostasis might underlie
      the near permanence of the obese body weight. Such neural plasticity can occur
      during both nervous system development and in adult life. Maternal diabetes,
      obesity, and undernutrition have all been associated with obesity in the
      offspring of such mothers, especially in genetically predisposed individuals.
      Altered brain neural circuitry and function often accompanies such obesity. This
      enhanced obesity may then be passed on to subsequent generations in a feed
      forward, upward spiral of increasing body weight across generations. Such
      findings suggest a form of "metabolic imprinting" upon genetically predisposed
      neural circuits involved in energy homeostasis. Centrally acting drugs used for
      obesity treatment lower the defended body weight and alter the function of neural
      pathways involved in energy homeostasis. But they generally have no permanent
      effect on body weight or neural function. Thus, early identification of obesity
      prone mothers, infants, and adults and treatment of early obesity may be the only
      way to prevent the formation of permanent neural connections that promote and
      perpetuate obesity in genetically predisposed individuals.

PMID- 10933312
TI  - Pre-emptive liver transplantation in primary hyperoxaluria type 1: a
      controversial issue.

PMID- 10933313
TI  - Compliance in pediatric transplant.

PMID- 10933314
TI  - Liver transplantation: to do or not to do?

PMID- 10933315
TI  - Surveillance endomyocardial biopsy in pediatric heart transplantation: fashion or
      foible?

PMID- 10933316
TI  - Long-term results of pre-emptive liver transplantation in primary hyperoxaluria
      type 1.
AB  - In primary hyperoxaluria type 1 (PH 1), deficiency or mistargeting of hepatic
      alanine glyoxylate aminotransferase (AGT) results in over-production of oxalate
      and hyperoxaluria, leading to nephrocalcinosis and development of end-stage renal
      disease (ESRD) in the majority of patients. Renal transplantation (Tx) alone
      carries a high risk of disease recurrence as the metabolic defect is not cured.
      Therefore, combined liver/kidney Tx is recommended for patients with ESRD. An
      alternative approach is to cure PH 1 by pre-emptive isolated liver Tx (PLTx)
      before ESRD has occurred, but this approach has been carried out only
      occasionally and there are no uniformly accepted recommendations concerning the
      timing of this procedure. We report follow-up 3-5.7 yr after performing
      successful PLTx in four children (at the age of 3-9 yrs) with PH 1 prior to the
      occurrence of ESRD (glomerular filtration rate [GFR] range 27-98 mL/min/1.73 m2).
      There was no mortality or long-term morbidity associated with the Tx procedure.
      Plasma and urinary oxalate levels normalized rapidly within 4 weeks, and renal
      function did not deteriorate under immunosuppression, even in one patient with
      advanced chronic renal failure (GFR 27 mL/min/1.73 m2) who showed a stable course
      for more than 5.7 yrs. Although treatment must be individualized in this severe
      metabolic disorder, and PLTx has to be regarded as an invasive procedure, we
      consider that PLTx should be offered and considered early in the course of PH 1.
      PLTx cures the metabolic defect in PH 1 and can help to prevent, or at least
      delay, the progression to ESRD and systemic oxalosis.

PMID- 10933317
TI  - A comparison of microbiologic flora of the sinuses and airway among cystic
      fibrosis patients with maxillary antrostomies.
AB  - The placement of maxillary antrostomies among cystic fibrosis (CF) patients has
      been used as a treatment to allow localized antibiotic lavage of infected sinus
      passages. This procedure is increasingly recommended by lung transplantation
      centers as a prerequisite prior to accepting a CF patient as a candidate for
      transplantation. Our study attempts to define the degree of identity between
      sinus, endotracheal and sputum cultures from 35 patients. The samples (n = 137)
      were collected within two weeks of each other. An analysis of the microbiologic
      type, strain, and antibiotic resistance patterns was undertaken. Randomization
      analysis was performed and a p-value of < 0.05 was considered significant. The
      results indicated a high degree of correlation between sinus-sputum pairs (n =
      55) and endotracheal samples (p < 0.008). This study provides evidence that there
      is a potential for cross-infection between sinus passages and the lower airway.
      The localized irrigation of CF sinus cavities post-transplantation may be
      warranted in an attempt to reduce bacterial counts and potential direct infection
      of the allograft. However, it is unlikely that this will eliminate this risk
      because bacterial colonization continues and the CF trachea is another source of
      infection.

PMID- 10933318
TI  - Endomyocardial biopsy in pediatric heart transplant recipients: a useful
      exercise? (Analysis of 1,169 biopsies).
AB  - The objective of this study was to define the diagnostic yield for endomyocardial
      biopsy (EMB) procedures performed for various indications in a large pediatric
      heart transplant population. Endomyocardial biopsy procedure has been employed as
      the 'gold standard' for rejection surveillance. Previous studies have questioned
      the value of surveillance EMB beyond the early post-transplant period. We
      retrospectively reviewed data on 82 pediatric heart transplant recipients with
      serial EMB. A total of 1,169 EMB were performed during a follow-up period of 2
      149 months (median 41 months). EMB were classified by age at transplantation,
      time from transplant, immunosuppressive regimen used [tacrolimus vs. cyclosporin
      A (CsA)] and indication, i.e. surveillance, follow-up after rejection or lowering
      of immunosuppression, non-specific clinical symptoms and graft dysfunction.
      During the first year after heart transplantation, surveillance EMB demonstrated
      significant rejection [International Society for Heart and Lung Transplantation
      (ISHLT) grade > or = 3A] in 18% of biopsies with the yield being 14-43% for all
      other indications. Surveillance EMB 1-5 yr post-transplantation were found to
      have a lower diagnostic yield in infants (4%, vs. 13% in children) and in
      patients with favorable first-year rejection history (9% vs. 17% in 'frequent
      rejectors'). Tacrolimus-based immunosuppression was associated with significantly
      less rejection, but only in the first year post-transplantation (14% in
      tacrolimus vs. 24% in CsA surveillance EMB, p = 0.035). Surveillance EMB remains
      an important diagnostic tool for rejection surveillance during the first 5 years
      after pediatric heart transplantation. Endomyocardial biopsy is particularly
      warranted after reduction of immunosuppression and for monitoring for ongoing
      rejection after treatment of acute rejection episodes.

PMID- 10933319
TI  - Lipoprotein abnormalities are highly prevalent in pediatric heart transplant
      recipients.
AB  - The role of hyperlipidemia in graft coronary artery disease (GCAD) is
      controversial although hyper-triglyceridemia is an independent risk factor.
      Recent studies show that 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)
      inhibitors decrease the incidence of GCAD in adults. The incidence of GCAD in
      pediatric patients is lower than in adults; it is not clear whether age-related
      differences in lipid metabolism account for some of this protection. This study
      was performed to: characterize the lipoprotein profile in children after heart
      transplantation; demonstrate that total cholesterol (TC) is a poor marker for
      underlying lipoprotein abnormalities; and to compare lipid abnormalities in
      patients who had been converted from cyclosporin A (CsA) to tacrolimus. Seventy
      one determinations of fasting lipoprotein profiles were performed in a cohort of
      28 children. Each child had at least two determinations on separate occasions.
      TC, low-density lipoprotein (LDL), and serum triglyceride (TG) levels were
      categorized as abnormal if greater than the 75th percentile for age and gender. A
      high-density lipoprotein (HDL) level less than the 25th percentile was considered
      abnormal. Immunosuppression included CsA or tacrolimus, azathioprine, and
      prednisone. We found that 90% of the patients studied had abnormalities of either
      TG or HDL. In contrast, LDL tended to be normal when adjusted for age and gender.
      TC was a poor indicator of any underlying abnormality in TG, LDL, or HDL. In
      patients converted to tacrolimus, no significant differences were found in the
      levels of TG, LDL or HDL compared with each patient's respective values while
      receiving CsA. Hence, lipoprotein abnormalities among pediatric heart transplant
      recipients are highly prevalent. TC is a poor screening tool in the evaluation
      for lipid abnormalities. Lipoprotein profiles remain statistically unchanged
      after conversion from CsA to tacrolimus.

PMID- 10933320
TI  - Non-adherence in pediatric liver transplant recipients--an assessment of risk
      factors and natural history.
AB  - Despite the fact that non-adherence to medical therapy is one of the major causes
      of late morbidity and mortality in pediatric liver transplant recipients, little
      is known of the risk factors involved in this behavior. Three cases of fatal non
      adherence are reported. Factors associated with non-adherence were investigated
      by performing a retrospective chart review of a panel of 27 variables in an age
      matched cohort of 15 pediatric liver transplant recipients. The most striking
      differences between the severely non-adherent group and the age-matched cohort
      included history of substance abuse, child abuse (physical or sexual), not having
      two parents at home, having received public assistance, having been diagnosed
      with a psychiatric disorder, and history of school dropout. In addition it
      appeared that a pretransplant diagnosis of autoimmune hepatitis was associated
      with more significant medical sequelae related to non-adherence. These findings
      are preliminary owing to the retrospective design of this study, but could be
      used as a starting point for a prospective study of this important phenomenon.

PMID- 10933321
TI  - Conversion from cyclosporin A to tacrolimus in pediatric liver transplantation.
AB  - The dosing regimen for conversion from cyclosporin A (CsA) to tacrolimus
      immunosuppression was studied in 12 pediatric liver allograft recipients.
      Patients were stratified according to their age. Tacrolimus was started orally at
      a dosage of 0.05 mg/kg b.i.d., 12 h after stopping CsA administration and
      increased thereafter if needed. Tacrolimus and CsA concentrations were assayed by
      immunoassay using, respectively, an IMx and a TDx autoanalyzer (Abbott-France).
      Mean CsA concentration was in the therapeutic range 12 h prior to and at the time
      of introduction of tacrolimus. After 72 h of tacrolimus therapy, CsA
      concentrations were undetectable whereas mean tacrolimus concentration was 10.4
      ng/mL with a mean dose of 0.09 mg/ kg b.i.d. The decline of CsA concentration was
      clearly biphasic. A slower decline in CsA concentration was detected after
      initiation of tacrolimus therapy, suggesting an inhibition of CsA metabolism by
      tacrolimus. No nephrotoxicity was observed. This dosage regimen allowed effective
      immunosuppression while avoiding additive nephrotoxicity.

PMID- 10933322
TI  - Fatal deterioration of neurological disease after orthotopic liver
      transplantation for valproic acid-induced liver damage.
AB  - We describe a 12-year-old girl with an early onset neurologic disease of slow
      progressiveness and electro-encephalography showing epileptic activity. The girl
      developed fulminant liver failure 5 months after the start of valproic acid
      treatment. Repeated mitochondrial assays failed to prove a mitochondrial
      disorder, but muscle biopsies were slightly pathological. Liver histology
      indicated acute-on-chronic liver disease. Six weeks after a successful orthotopic
      liver transplantation her neurological condition deteriorated rapidly, soon
      leading to generalized cortical disease and death. Post-mortem brain examination
      showed advanced central nervous destruction. We suggest that this is a late-onset
      Huttenlocher variant of Alpers' syndrome, where fulminant liver failure can be
      triggered by valproic acid, and orthotopic liver transplantation can subsequently
      trigger a fatal neurologic deterioration. Our case illustrates that when a
      referral center receives a previously unknown patient with hepatocellular
      insufficiency, it might be impossible to differentiate between fulminant vs.
      acute-on-chronic liver failure, and the decision whether to perform a liver
      transplantation or not would become difficult.

PMID- 10933323
TI  - Graft failure secondary to necrotizing enterocolitis in multi-visceral
      transplantation recipients: two case reports.
AB  - We report on two recipients of multi-visceral grafts who exhibited sudden onset
      of acute abdomen discomfort 2 weeks post-transplantation after a fairly
      uneventful immediate post-operative course. Both patients were shown to have
      pneumatosis intestinalis and one had air in the portal vein. Both patients
      underwent exploration, which showed non-viable intestine (terminal ileum and
      colon in the first patient and the entire small intestine distal to the ligament
      of Treitz in the second patient). There was no vascular thrombosis. The necrotic
      intestine was resected in both cases. The first patient developed sepsis and died
      15 days later despite the rescue efforts. The second patient was re-transplanted
      twice and is doing well. The histopathology of the segments involved revealed
      cryptitis, vasculitis, and features of transmural necrosis. Accordingly, both
      clinical and pathologic features are diagnostic of necrotizing enterocolitis. To
      our knowledge this is the first report of this complication following intestinal
      or multi-visceral transplantation.

PMID- 10933324
TI  - A decade of living donor transplantation in North American children: the 1998
      annual report of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS).
AB  - This report of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) covers the years 1987-1997, and analyzes data on 2,904 living donor
      (LD) transplants performed in 2,779 patients. Since 1991, approximately 300 LD
      transplants have been performed each year at the participating centers of the
      NAPRTCS. Caucasian children account for 72% of all LD recipients while African
      American children constitute only 11%. There has been a gradual decline in the
      number of transplants performed in children under the age of 6 years from a peak
      of 30% in 1987, to 21% in 1997. Preoperative calcineurin inhibitor therapy has
      dropped from 71% in 1987 to 38% in 1997. Through 1996, at six months post
      transplant 97% of recipients were receiving prednisone, 88% were maintained on
      cyclosporin A, and 79% were receiving azathioprine. Of patients transplanted in
      1997, 47% are maintained on mycophenolate and 10% are maintained on tacrolimus.
      By day 15, 20% of index transplant patients have had an acute rejection and by
      the end of the first year 47% have had a rejection episode. Among patients
      transplanted in 1995-1996, 40% had a rejection in the first year. Nine per cent
      of rejection episodes are irreversible in children under 2 years of age and 5% of
      the episodes are irreversible in 25-year-old children. Estimated graft survival
      probability at 1 year is 91%, at 3 years it is 84% and at 5 years it is 78.5%.
      Rejection accounts for 33% of graft loss and recurrence constitutes another 10%.
      Influential prognostic variables for graft survival are race (African-American
      vs. others, relative risk (RR) = 2.0, p < 0.001), > 5 random transfusions (RR =
      1.6, p < 0.001, T cell induction therapy (RR = 0.78, p = 0.01), and later year of
      entry (1989-1990 vs. 1994-1995, RR = 0.95, p = 0.04). Patient survival at 1 and 3
      years was 97% and 96.5%, respectively, however, the 3-year patient survival of
      children under 2 years was 89%. The mean height deficit baseline (n=2,677) was 
      1.86, at 1 year post-transplant (n=1,459) it was -1.80, and at 5 years post
      transplant (n=592) it was -2,06. This report, devoted specifically to LD
      pediatric transplants, raises the issues regarding the use of immunosuppression
      such as preoperative calcineurin inhibitors and T-cell antibodies. Studies to
      address the high incidence of chronic rejection and recurrence of original
      disease are necessary. Additional areas of concern are the high infant mortality
      and continued growth retardation post-transplantation.

PMID- 10933326
TI  - Should cardiologists forget about platelets and take an interest in blood
      leukocytes?

PMID- 10933325
TI  - Continuing improvement in cadaver donor graft survival in North American
      children: the 1998 annual report of the North American Pediatric Renal Transplant
      Cooperative Study (NAPRTCS).
AB  - This report of the North American Pediatric Renal Transplant Cooperative Study
      (NAPRTCS) covers the years 1987-1997, and analyses data on 3,133 cadaver donor
      (CD) transplants performed in 2,736 patients. There has been a steady decline in
      the number of CD transplants in children since 1996. Kidneys recovered from
      donors under 10 years of age accounted for 35% of all transplants in 1987,
      whereas by 1996 they comprised less than 20%. Caucasian children received 54% of
      CD transplants, whereas African-American children received 21%. Children under 6
      years of age received 17% of CD transplants. Approximately half (46%) of the
      patients were induced with a T-cell antibody, and at 7 years post-transplant
      triple therapy is used in 70% of those with a functioning graft. Cyclosporin A is
      the primary immunosuppressant, with 92% of the patients being maintained on it at
      5 years post-transplant. Among patients receiving a transplant in 1997, 11% were
      initiated with another calcineurin inhibitor, tacrolimus. At 15 days post
      transplant 20% of the patients have had a rejection episode and by day 45, 46%
      have had an acute rejection. The probability of developing a rejection within the
      first year was reduced from 71% in 1987-1988 to 47% in 1995-1996.

PMID- 10933327
TI  - A new aortic Dacron conduit for surgical treatment of aortic root pathology.
AB  - BACKGROUND: This article describes a new aortic Dacron conduit that has been
      designed for use in all types of surgery of the aortic root. Its use is aimed at
      facilitating the surgical procedure and obtaining a natural anatomical
      configuration of the aortic root. METHODS: The modified Dacron conduit is
      obtained by adding a smaller piece of Dacron tube that is resilient in the
      horizontal plane to one end of a standard Dacron conduit. Upon implantation, this
      small piece of Dacron conduit will stretch in the horizontal plane creating
      pseudosinuses and a new sinotubular junction. This modified conduit has been used
      in 4 cases for a Bentall operation in association with a mechanical or a
      biological valve, in 4 cases in a Yacoub type of valve sparing procedure and in 1
      case in a David type I of valve sparing procedure. All patients had aortic root
      aneurysm with severe aortic regurgitation. There were 6 males and 3 females with
      a mean age of 61 +/- 16 years. In most cases a 28 mm Dacron conduit was used.
      RESULTS: All surgery was carried out without mortality or morbidity. The creation
      of pseudosinuses was confirmed intraoperatively by visual inspection.
      Transesophageal echocardiography in patients who had undergone the Bentall
      operation showed a normally functioning valve prosthesis with a suitably shaped
      aortic root. In patients who had undergone the valve sparing procedures it showed
      a competent aortic valve, the creation of pseudosinuses of normal shape and
      depth, and the presence of a well defined sinotubular junction. Angiography
      confirmed that the prosthetic aortic root perfectly resembled the normal root
      anatomy. CONCLUSIONS: This modified new aortic root conduit appears to perfectly
      reproduce a normal root anatomy without the need of modifying the original
      techniques.

PMID- 10933328
TI  - Cardiac pacing in heart failure patients with left bundle branch block: impact of
      pacing site for optimizing left ventricular resynchronization.
AB  - BACKGROUND: Acute left ventricular pacing has been associated with hemodynamic
      improvement in patients with congestive heart failure and wide QRS complex. We
      hypothesized that pacing two left ventricular sites simultaneously would produce
      faster activation and better systolic function than single-site pacing. METHODS:
      We selected 14 heart failure patients (NYHA functional class III or IV) in normal
      sinus rhythm with left bundle branch block and QRS > 150 ms. An 8F dual
      micromanometer catheter was placed in the aorta for measuring +dP/dt (mmHg/s),
      aortic pulse pressure (mmHg), and end-diastolic pressure (mmHg). Pacing leads
      were positioned via coronary veins at the posterior base and lateral wall.
      Patients were acutely paced VDD at the posterior base, lateral wall, and both
      sites (dual-site) with 5 atrioventricular delays (from 8 ms to PR -30 ms). Pacing
      sequences were executed in randomized order using a custom external computer
      (FlexStim, Guidant CRM). RESULTS: Dual-site pacing increased peak +dP/dt
      significantly more than posterior base and lateral wall pacing. Dual-site and
      posterior base pacing raised aortic pulse pressure significantly more than
      lateral wall pacing. Dual-site pacing shortened QRS duration by 22 %, whereas
      posterior base and lateral wall pacing increased it by 2 and 12%, respectively (p
      = 0.006). CONCLUSIONS: In heart failure patients with left bundle branch block,
      dual-site pacing improves systolic function more than single-site stimulation.
      Improved ventricular activation synchrony, expressed by paced QRS narrowing, may
      account for the additional benefit of dual- vs single-site pacing in enhancing
      contractility. This novel approach deserves consideration for future heart
      failure pacing studies.

PMID- 10933329
TI  - Heart rate variability in patients with variant angina: effect of the presence of
      significant coronary stenosis.
AB  - BACKGROUND: The syndrome of variant angina occurs in patients with a wide
      spectrum of coronary disease ranging from angiographically normal coronary
      arteries to severe three-vessel disease. Survival and choice of therapy for these
      patients are determined by the extent of underlying fixed coronary obstruction.
      We examined whether heart rate variability (HRV) due to reduced vagal outflow may
      correlate with the severity of coronary stenoses in such patients. METHODS:
      Fifteen men and 2 women with clinically unstable variant angina underwent 24-hour
      Holter monitoring from which low and high-frequency power, standard deviation of
      mean 24-hour RR interval, proportion of adjacent RR intervals that differed by
      more than 50 ms, and mean root square of differences between successive RR
      intervals were extracted by power spectral analysis. Coronary angiography was
      later performed to determine coronary pathology and verify variant angina. As
      controls we studied an age-matched control group of 8 subjects (5 men, 3 women)
      with no clinical and/or electrocardiographic evidence of coronary heart disease
      or spasm as shown by negative treadmill exercise and hyperventilation tests.
      RESULTS: All measured components of HRV were significantly lower in the 9
      patients with severe coronary artery disease compared to the 8 patients with
      normal coronary arteries or < 40% stenosis. The two groups were otherwise similar
      in terms of age and clinical parameters. CONCLUSIONS: These preliminary findings
      on a small but carefully selected group of patients with variant angina indicate
      that the analysis of HRV can select patients with severe disease for a more
      intensive approach. These findings require confirmation on a larger patient
      series.

PMID- 10933331
TI  - Predictors of long-term clinical outcome in patients undergoing multiple vessel
      stenting for coronary artery disease.
AB  - BACKGROUND: Coronary artery stenting reduces the restenosis rate compared to
      coronary angioplasty alone. With the increased number of procedures completed
      with stent placement there has been a parallel increase in the number of
      procedures performed in patients with multivessel disease and therefore a rise in
      the number of patients receiving multiple stents. The clinical outcome and the
      predictors of the outcome of patients receiving multiple stents are not known.
      METHODS: To evaluate the clinical outcome of patients with multivessel coronary
      artery disease undergoing multiple stenting we studied 133 consecutive patients
      who had received > 1 stent in at least two vessels. A total of 375 coronary
      stents (2.8 stent per patient) were implanted in elective procedure situations.
      Clinical follow-up was complete in 100%. RESULTS: During follow-up 2 patients
      (1.5%) died (1 cardiac death), 4 patients (3%) had acute myocardial infarction,
      96 patients (72.1%) remained angina-free, and 31 patients (23.3 %) had recurrence
      of angina. Repeat revascularization procedure was performed in 45 patients
      (33.8%); 43 patients (32.3%) underwent coronary angioplasty; 2 patients (1.5%)
      underwent coronary artery bypass grafting. The female gender and the presence of
      diabetes were significant (p < 0.05) predictors for coronary angioplasty or
      coronary artery bypass grafting procedures during follow-up. Recurrence of angina
      was also significantly (p < 0.05) associated with unstable angina at the time of
      the first procedure as well as diabetes and the female gender. Diabetes, the
      female gender and unstable angina were highly predictive factors of major adverse
      cardiac events during follow-up. CONCLUSIONS: Multiple vessel stenting in
      patients with multivessel coronary artery disease is associated with an
      acceptable immediate and long-term clinical outcome and could be considered as an
      alternative therapeutic option in these patients. Predictors of an adverse long
      term outcome are the female gender and the presence of diabetes mellitus.

PMID- 10933330
TI  - Intravenous versus oral initial load of propafenone for conversion of recent
      onset atrial fibrillation in the emergency room: a randomized trial.
AB  - BACKGROUND: Non-valvular paroxysmal atrial fibrillation is a common clinical
      condition associated with a high risk of thromboembolism and hemodynamic problems
      which increase with the duration of arrhythmia. Therefore, even if arrhythmia
      ceases spontaneously within 24 hours in about half of the patients, a higher
      early conversion rate is desirable. Propafenone either by intravenous or oral
      load has been shown effective in conversion to sinus rhythm. METHODS: We
      consecutively randomized all emergency patients with non-valvular atrial
      fibrillation lasting no more than 48 hours to either intravenous or oral initial
      load of propafenone. They all received further oral doses if still on atrial
      fibrillation after the initial load. Exclusion criteria were: mean ventricular
      rate < 65 b/min, age > 75 years, recent acute myocardial infarction, overt heart
      failure, conduction defects, ventricular preexcitation, thyroid dysfunction,
      renal or hepatic insufficiency, pregnancy, current treatment with propafenone or
      other antiarrhythmic drugs, and intolerance to propafenone. Primary and secondary
      end-points were the conversion to sinus rhythm within 12 and 48 hours of
      randomization respectively. RESULTS: Ninety-seven patients were randomized to
      intravenous (n = 49) or oral (n = 48) treatment. Overall, sinus rhythm
      restoration occurred in 83.3% of patients within 12 hours and in 98.9% at 24
      hours. Recovery rate resulted significantly greater for intravenous treatment at
      1 and 3 hours (p < 0.001 and p = 0.001, respectively). At 6, 12 and 24 hours no
      significant difference between the two groups was observed (p = 0.77, p = 0.81
      and p = 0.99, respectively). No patient needed treatment suspension. CONCLUSIONS:
      In patients with recent-onset non-valvular atrial fibrillation treated with
      propafenone within 48 hours, conversion to sinus rhythm occurred in more than 80%
      within 12 hours. Even if intravenous initial load appears to be slightly more
      rapid, the oral way is easier to administer and cheaper. The choice may depend on
      the specific organization of the single emergency room.

PMID- 10933332
TI  - Assessment of echocardiographic abnormalities in patients with systemic lupus
      erythematosus: correlation with levels of antiphospholipid antibodies.
AB  - BACKGROUND: The aim of this study was to evaluate the incidence of morphologic
      and functional cardiac abnormalities in patients with systemic lupus
      erythematosus and correlate the data with antiphospholipid antibody (aPL) levels.
      METHODS: Ninety-one patients with systemic lupus erythematosus were enrolled and
      divided into two groups according to the presence (Group 1, n = 45) or absence of
      aPL (Group 2, n = 46). All patients underwent standard two-dimensional and
      Doppler echocardiographic examination. aPL were detected by a standardized and
      validated ELISA test. Five patients with regional ventricular dysfunction also
      underwent coronary angiography. The chi2 test was used for the statistical
      analysis of the data. For smaller groups of samples the Fisher's exact test was
      employed. RESULTS: Pericardial effusion was detected in 19 patients without any
      statistical difference between the two groups. A valvular involvement was present
      in 39 patients: a moderate-severe degree was more frequent in Group 1 (p = 0.02).
      Regional wall motion abnormalities were observed in 8 patients: only 1 in Group 2
      and 7 in Group 1 (p = 0.03). Coronary angiography showed normal arteries in all
      patients of Group 1. CONCLUSIONS: aPL play a role in the pathogenesis of the
      severity of valvular lesions as well as in regional myocardial dysfunction,
      suggesting a small vessel disease.

PMID- 10933333
TI  - Cardiac abnormalities in type 1 diabetes.
AB  - BACKGROUND: Left ventricular (LV) structural and hemodynamic consequences of type
      1 diabetes mellitus are not fully understood. METHODS: To evaluate LV geometry,
      systolic and diastolic function in type 1 diabetes, Doppler echocardiograms were
      performed in 40 normotensive, type 1 diabetic patients without coronary heart
      disease or valvular lesions (22 men, 18 women, mean age 43 +/- 6 years, body mass
      index 24.7 +/- 2.8 kg/m2) and in 40 age and sex-matched non-diabetic normotensive
      controls (22 men, 18 women, mean age 43 +/- 5 years, body mass index 23.2 +/- 2.8
      kg/m2), in a case-control design. RESULTS: Patients had higher systolic blood
      pressure than controls (p < 0.03) and comparable diastolic blood pressure and
      heart rate. LV dimension and mass were higher in patients than in controls (both
      p < 0.0001) whereas relative wall thickness did not differ. For comparable levels
      of end-systolic stress, patients exhibited a higher ejection fraction than
      controls (p < 0.01) and normal midwall shortening. Cardiac output was also higher
      (p < 0.001), whereas total peripheral resistance was lower in patients than in
      controls (p < 0.0001). Isovolumic relaxation time and E deceleration were
      prolonged in patients and peak A velocity was greater than in controls (all p <
      0.01), whereas the difference in duration between A and pulmonary vein peak
      reverse flow at atrial contraction was comparable. In subgroup analyses, all
      reported features were independent of a) presence of target organ damage; b)
      duration of disease; c) levels of glycosylated hemoglobin. CONCLUSIONS: In
      normotensive patients with type 1 diabetes: 1) there was a moderate increase in
      LV mass; 2) LV chamber function was supernormal and wall mechanics was normal; 3)
      LV active relaxation was impaired but chamber stiffness was normal.

PMID- 10933334
TI  - Images in cardiovascular medicine. A case of free-floating left atrial thrombus
      in mitral valve stenosis.

PMID- 10933335
TI  - Gamma-hydroxybutyric acid in the treatment of alcoholism: dosage fractioning
      utility in non-responder alcoholic patients.
AB  - Gamma-hydroxybutyric acid (GHB) has recently been introduced in clinical practice
      for alcoholism management, due to its utility in inducing abstinence from
      alcohol. In the present study we investigated the usefulness of greater dosage
      fractioning of GHB in non-responder alcoholics to the usual three administrations
      per day. A total of 154 alcoholics were admitted to the study and were treated
      with GHB (50 mg/Kg orally administered three times per day) for 8 weeks (phase
      1); the patients who continued to drink alcohol in phase 1 were administered the
      same dose of GHB divided into six times per day for another 8 weeks (phase 2). Of
      the 154 patients, 115 completed phase 1; 78 (67.8%) of these began and maintained
      abstinence (group A) while 37 subjects (32.2%) continued to drink alcohol (group
      B) showing a craving significantly higher than group A at the end of phase 1 (P <
      0.001); in these patients the major fractioning of the drug in phase 2 caused a
      significant reduction in craving (P < 0.005) and 26 (70.2%) began and maintained
      abstinence. Moreover no significant differences in final craving score between
      group A and B was observed. Within the limits of an open study, our data show
      that non-responder subjects to the conventional fractioning of GHB seem to
      benefit from the greater fractioning of the drug and seem to indicate the need
      for a slow-release form of GHB with a prolonged action.

PMID- 10933336
TI  - Heroin snorters versus injectors: comparison on drug use and treatment outcome in
      age-matched samples.
AB  - Drug use histories and treatment outcomes were compared for age, race and gender
      matched samples of intravenous (IV; n = 28) versus intranasal (IN; n = 28) opiate
      abusers entering a 3-day inpatient detoxification unit. Data were derived from
      the Addiction Severity Index (ASI) interview. Both groups reported daily heroin
      use prior to detoxification, but IV users reported more days of alcohol and
      multiple drug use during the past 30 days. Despite age matching, IV users also
      started using alcohol at an earlier age and accumulated more lifetime months of
      regular alcohol, cocaine and multidrug use. IV users were more likely to enter
      treatment following the detox, but no significant outcome differences were noted
      at 1 and 3 months post-detoxification. The results show that intravenous, as
      compared to intranasal, opiate users have both a more severe pattern and a more
      extensive history of the use of non-opiate drugs.

PMID- 10933338
TI  - Differential tolerance to morphine's immunomodulatory effects following
      continuous administration.
AB  - Rats were continuously infused with either morphine or saline via an osmotic
      minipump for 20 consecutive days. Effects on immune status were assessed on the
      twentieth day of the chronic administration period following a bolus injection of
      morphine administered 1 h prior to sacrifice. The morphine injection suppressed
      measures of splenic natural killer (NK) cell activity, mitogen-stimulated T-cell
      proliferation, and gamma-interferon (IFN) production in rats that received saline
      via the minipump. In rats that received chronic morphine via the minipump, the
      morphine injection also suppressed mitogen-stimulated splenocyte proliferation
      and gamma-IFN production but did not suppress NK cell activity. These data
      indicate that chronic morphine administration via osmotic minipumps leads to
      differential tolerance to the immunomodulatory effects of morphine. These
      findings support previous results indicating differential tolerance development
      within the immune system following chronic morphine administration via the
      drinking water.

PMID- 10933337
TI  - Butorphanol agonist effects and acute physical dependence in opioid abusers:
      comparison with morphine.
AB  - This study compared the direct effects and acute physical dependence of
      butorphanol and morphine, opioids with differing actions at mu versus kappa
      receptors. Six non-dependent heroin-using volunteers were exposed to six
      conditions in a within-subject, Latin square design using double-blind
      procedures. In each session, agonist effects of single i.m. injections of
      butorphanol (3 and 6 mg/70 kg), morphine (15 and 30 mg/70 kg), lorazepam (4 mg/70
      kg) or saline were evaluated. Butorphanol and morphine produced effects of
      comparable magnitude on miosis and reports of 'any drug effect'. Volunteers
      reported dysphoria, confusion and sedation after butorphanol, subjective effects
      that overlapped with those of lorazepam, whereas morphine produced euphoria and
      stimulation. Acute physical dependence (i.e. precipitated withdrawal responses to
      naloxone 10 mg/70 kg i.m. administered 6 h after each treatment) significantly
      increased after 30 mg/70 kg morphine but not after butorphanol treatments. These
      differences in naloxone sensitivity are likely due to differences in opioid
      receptor (mu versus kappa) activity, affinity and efficacy of these compounds.
      Pharmacological ramifications of these results are discussed.

PMID- 10933339
TI  - Dopaminergic and serotonergic alterations in the rat brain during ethanol
      withdrawal: association with behavioral signs.
AB  - Changes in dopaminergic and serotonergic levels and metabolites in cerebral
      cortex, corpus striatum and hippocampus were investigated during the first 6-h of
      withdrawal in ethanol-dependent Wistar rats. Ethanol was given by a liquid diet
      for 21 days. The concentration of ethanol was 7.2% (v/v) for the last 15 days of
      the exposure. After 2, 4 and 6 h of ethanol withdrawal, and after audiogenic
      stimulus (100 dB for 60 s) at 6 h of ethanol withdrawal, various brain regions
      were assayed for levels of dopamine (DA), DOPAC, HVA, serotonin (5-HT) and 5
      HIAA. Behavioral signs of ethanol withdrawal and blood ethanol levels were also
      evaluated in other parallel groups of ethanol-dependent rats. Significant
      decreases in 5-HT levels and significant increases in HVA levels in striatum were
      found during the first 6 h of ethanol withdrawal and after the audiogenic
      seizures. In hippocampus, 5-HIAA levels were significantly reduced after 2 h of
      ethanol withdrawal and after the audiogenic seizures. 5-HIAA levels significantly
      increased after 2 h of ethanol withdrawal in cerebral cortex. Significant
      increases in both DA and 5-HT levels were also found in cerebral cortex after the
      audiogenic seizures. The results suggest that the levels of DA, 5-HT and their
      metabolites are altered by ethanol withdrawal. Furthermore, this may suggest that
      DA and 5-HT may be involved in the first 6 h of ethanol withdrawal syndrome in
      rats.

PMID- 10933340
TI  - Flunitrazepam and triazolam: a comparison of behavioral effects and abuse
      liability.
AB  - The performance, observer-rated, and participant-rated effects of orally
      administered placebo, and two benzodiazepines, flunitrazepam (2, 4 and 8 mg/70
      kg) and triazolam (0.25, 0.5 and 1 mg/70 kg), were compared in 14 sedative drug
      abusers using a double-blind crossover design. Both flunitrazepam and triazolam
      produced dose-related decrements in memory and psychomotor/cognitive performance,
      and increases in many participant- and observer-rated measures. Effects of
      flunitrazepam had an earlier onset and a longer duration than those of triazolam.
      Although there was evidence that the flunitrazepam doses selected for study were
      somewhat higher overall relative to the selected triazolam doses, analysis of the
      participant-rated measures collected 24 h after drug administration (next-day)
      suggests that flunitrazepam may have a greater abuse liability than triazolam
      when abuse liability is assessed 24 h after drug administration. The highest
      flunitrazepam dose produced effects that were significantly greater than those of
      the highest triazolam dose on next-day ratings of good effects, take again, and
      worth; all tested flunitrazepam doses produced effects greater than any triazolam
      dose on next-day ratings of liking and take again. The highest flunitrazepam
      dose, but no triazolam dose, significantly increased the maximum dollar value at
      which participants chose drug over money in a Drug versus Money Choice Procedure.

PMID- 10933341
TI  - Ketoconazole reduces low dose cocaine self-administration in rats.
AB  - Ketoconazole is an oral antimycotic agent approved by the FDA for the treatment
      of fungal disease which also blocks the synthesis of adrenocorticosteroids and
      functions as a glucocorticoid receptor antagonist. In these experiments, adult
      male Wistar rats were allowed alternating 15-min periods of access to food
      reinforcement and cocaine self-administration (0.125, 0.25 or 0.5 mg/kg per
      infusion) during daily 2-h sessions. A 1-min timeout separated access to the two
      reinforcers. Pretreatment with ketoconazole (25 mg/kg, i.p.) significantly
      decreased plasma corticosterone and reduced low dose (i.e. 0.125-0.25 mg/kg per
      infusion) cocaine self-administration without affecting food-reinforced
      responding. In fact, pretreatment with ketoconazole resulted in rates and
      patterns of self-administration at these doses that were indistinguishable from
      those observed during cocaine extinction. However, cocaine self-administration at
      the highest dose tested in these experiments (i.e. 0.5 mg/kg per infusion) was
      not significantly affected by ketoconazole. These data suggest the potential
      utility of ketoconazole or related drugs as adjuncts in the treatment of cocaine
      abuse and further underscore the role for corticosterone in cocaine
      reinforcement.

PMID- 10933342
TI  - The onset of heroin use and criminal behaviour: does order make a difference?
AB  - The extent to which the onset of criminality with respect to heroin use accounts
      for heterogeneity within a heroin-using population was investigated among 400
      community and incarcerated methadone maintenance patients. Those for whom crime
      preceded heroin use (primary antisocials) were younger and more likely to be male
      than those for whom heroin use preceded crime (secondary antisocials). Primary
      antisocials were also more likely to have committed violent crime and to qualify
      for a diagnosis of antisocial personality disorder (ASPD). It is concluded that
      taking the order of onset of heroin use and criminality into account may reduce
      the risk of overdiagnosing ASPD among this population and help clarify the
      relationship between drug use and crime.

PMID- 10933343
TI  - Management of coronary artery disease: therapeutic options in patients with
      diabetes.
AB  - OBJECTIVES: The aim of this review is to discuss the particularities of coronary
      artery disease (CAD), the effect of intensive medical management and the outcome
      of percutaneous and surgical revascularization in patients with diabetes mellitus
      (DM). BACKGROUND: CAD represents the leading cause of death in patients with DM.
      Numerous clinical, biological and angiographic risk factors have been shown to be
      associated with CAD in diabetic patients. METHODS: Metabolic abnormalities in
      patients with DM including insulin resistance, hyperglycemia and dyslipidemia are
      briefly discussed. Then the potential roles of medical management and of
      percutaneous and surgical coronary revascularization are more extensively
      reviewed. RESULTS: More vigorous control of hyperglycemia, hyperlipidemia,
      hypertension and other risk factors may be of crucial importance for risk
      reduction. Despite remarkable progress in recent years, the choice of a coronary
      revascularization strategy remains a challenge in these patients. Diabetic
      patients with CAD are predisposed to higher cardiovascular events after balloon
      angioplasty. Whether stenting and new antiplatelet drugs improve the results of
      percutaneous revascularization in this population needs further evaluation. The
      superiority of the surgical approach is also not definitely established.
      Therefore, many aspects of coronary revascularization are still unclear in these
      patients. CONCLUSIONS: The results of ongoing randomized trials comparing
      multiple coronary stents to bypass surgery will likely provide some answers to
      our questions and additional randomized trials evaluating intensive diabetic
      control with or without coronary revascularization are needed to determine the
      best therapeutic approach in these patients.

PMID- 10933344
TI  - Thrombolytic therapy in older patients.
AB  - OBJECTIVES: We compared outcomes following thrombolytic therapy and primary
      angioplasty with no reperfusion therapy in a population-based cohort of older
      patients presenting with acute myocardial infarction (AMI) and indications for
      acute reperfusion. BACKGROUND: Evidence supporting the efficacy of acute
      reperfusion (thrombolytic therapy or primary angioplasty) in the elderly with
      suspected AMI is not as strong as it is in younger groups. METHODS: From a
      national cohort of Medicare beneficiaries with AMI, we identified 37,983 patients
      age 65 or older who presented within 12 h of symptom onset with ST elevation or
      left bundle branch block. A total of 14,341 (37.8%) received thrombolytic therapy
      and 1,599 (4.2%) underwent primary angioplasty within 6 h of hospital arrival.
      RESULTS: After adjustment for demographic, clinical, hospital and physician
      factors, and co-interventions, thrombolytic therapy was not associated with a
      better 30-day survival (odds ratio [OR] 1.01; 95% confidence interval [CI]: 0.94
      to 1.09) compared with no therapy, whereas primary angioplasty was (OR 0.79; 95%
      CI: 0.66 to 0.94). At one year, both thrombolytic therapy (OR 0.84; 95% CI: 0.79
      to 0.89) and primary angioplasty (OR 0.71; 95% CI: 0.61 to 0.83) were associated
      with a survival benefit. CONCLUSIONS: In this national sample of older patients,
      those who received thrombolytic therapy or primary angioplasty had lower
      mortality at one year compared with those who did not receive a reperfusion
      strategy. However, only primary angioplasty was associated with better survival
      at 30 days. Our findings should heighten interest in further investigating the
      best approach to the treatment of older patients with suspected AMI and ST
      segment elevation or left bundle branch block.

PMID- 10933345
TI  - Massive pulmonary embolism: percutaneous emergency treatment by pigtail rotation
      catheter.
AB  - OBJECTIVES: This study was designed to assess the feasibility, efficacy and
      safety of mechanical fragmentation of pulmonary emboli using a new rotational
      pigtail catheter system. BACKGROUND: Acute massive pulmonary embolism associated
      with right ventricular dysfunction is frequently lethal, despite high-dose
      thrombolytic therapy. Adjunctive catheter fragmentation may prevent a fatal
      outcome. METHODS: In 20 patients (age 58.9+/-10.5 years) with severe hemodynamic
      impairment, massive pulmonary emboli were fragmented by mechanical action of the
      rotating pigtail. Fifteen patients received thrombolysis after embolus
      fragmentation or no thrombolysis at all (noninterference group). RESULTS:
      Prefragmentation pulmonary arterial occlusion was 68.6 +/- 11.3% for both lungs.
      Pulmonary placement and navigation of the fragmentation catheter was easy and
      rapid. Fragmentation time was 17+/-8 min. The noninterference group showed a
      decrease pre- to postfragmentation of shock index from 1.28+/-0.53 to 0.95+/-0.38
      (p = 0.011), mean pulmonary artery pressure from 31+/-5.7 to 28+/-7.5 mm Hg (p =
      0.02) and a recanalization by fragmentation of 32.9+/-11.8% (mean angiographic
      score per treated lung from 7.4 to 5.0). Overall mortality was 20%. CONCLUSIONS:
      Fragmentation by pigtail rotation catheter provided for a rapid and safe
      improvement of the hemodynamic situation and an average recanalization of about
      one-third of the pulmonary embolic occlusion. The method appears useful
      especially in high-risk patients threatened by right ventricular failure, to
      accelerate thrombolysis, and as a minimal-invasive alternative to surgical
      embolectomy.

PMID- 10933346
TI  - Clinical benefit of glycoprotein IIb/IIIa blockade with Abciximab is independent
      of gender: pooled analysis from EPIC, EPILOG and EPISTENT trials. Evaluation of
      7E3 for the Prevention of Ischemic Complications. Evaluation in Percutaneous
      Transluminal Coronary Angioplasty to Improve Long-Term Outcome with Abciximab GP
      IIb/IIIa blockade. Evaluation of Platelet IIb/IIIa Inhibitor for Stent.
AB  - OBJECTIVES: We sought to determine the efficacy and safety of platelet
      glycoprotein IIb/IIIa receptor (GP IIb/IIIa) blockade with abciximab in women
      undergoing percutaneous coronary intervention. BACKGROUND: Although gender
      differences in response to platelet glycoprotein IIb/IIIa receptor blockade have
      been described, there have been no large clinical studies to assess these
      differences. METHODS: Outcomes were determined using meta-analysis technique.
      RESULTS: In the pooled analysis, the primary end point of death, myocardial
      infarction (MI) or urgent revascularization within 30 days was reduced from 11.3%
      to 5.8% (p<0.001) in men and from 12.7% to 6.5% (p<0.001) in women treated with
      abciximab. At six months, death, MI or urgent revascularization was reduced from
      14.1% to 8.3% (p<0.001) in men and 16.0% to 9.9% (p<0.001) in women receiving
      abciximab. At one year, mortality was reduced from 2.7% to 1.9% (p = 0.06) in men
      and 4.0% to 2.5% (p = 0.03) in women treated with abciximab. Major bleeding
      events occurred in 2.9% versus 3.0% (p = 0.96) of women and 2.7% versus 1.3% (p =
      0.003) of men treated with placebo versus abciximab, respectively. Minor bleeding
      events occurred in 4.7% versus 6.7% (p = 0.01) of women and 2.3% versus 2.2% (p =
      0.94) of men treated with placebo versus abciximab, respectively. CONCLUSIONS:
      This pooled analysis demonstrated no gender difference in protection from major
      adverse outcomes with GP IIb/IIIa inhibition with abciximab. Although women had
      higher rates of both major and minor bleeding events with abciximab compared with
      men, major bleeding in women was similar with and without abciximab. There was a
      small increased risk of minor bleeding with abciximab in women.

PMID- 10933347
TI  - Long-term clinical outcome after endoluminal reconstruction of diffusely
      degenerated saphenous vein grafts with less-shortening wallstents.
AB  - OBJECTIVES: This study was designed to evaluate the immediate and long-term
      clinical results of patients undergoing endoluminal reconstruction in diffusely
      degenerated saphenous vein grafts (SVGs) with elective implantation of one or
      more less-shortening Wallstents. BACKGROUND: The optimal treatment strategy for
      patients with diffusely degenerated SVGs is controversial. Endoluminal
      reconstruction by stent implantation is one proposed strategy; however, there are
      few data regarding long-term clinical outcome. METHODS: Between May 1995 and
      September 1998, 6,534 consecutive patients underwent angioplasty in our
      institution, including 440 who were treated for SVG lesions. Of these, 126 (115
      men, 11 women, median age 69.5 years, range: 33-86 years) with old SVGs (mean
      age: 13+/-5 years) diffusely degenerated stenosed or occluded (mean lesion
      length: 27+/-12 mm) were treated electively with implantation of one or multiple
      (total 197) less-shortening Wallstents. RESULTS: Before discharge, 13 patients
      (10.3%) sustained at least one major cardiovascular event, including 4 deaths
      (3.2%), 11 myocardial infarctions (MI) (8.7%), and 3 repeat revascularizations
      (target vessel = 1, nontarget vessel = 2, 2.4%). Surviving patients were followed
      for 22+/-11 months: 13 patients (11.1%) died, 11 (9.4%) sustained an MI, 37
      underwent angioplasty (31.6%), and 4 (3.4%) underwent bypass surgery. The
      estimated three-year event-free survival rates (freedom from death, and freedom
      from death/MI/target vessel revascularization) were (mean +/- SE) 81.1+/-7.8% and
      43.2+/-18.5%, respectively. CONCLUSIONS: The long-term clinical outcome of
      patients undergoing endoluminal reconstruction in diffusely degenerated SVG is
      relatively poor, mainly because of a high incidence of death or MI and the
      frequent need for repeat angioplasty. It is unlikely that percutaneous
      intervention alone will provide a satisfactory or definitive solution for these
      patients.

PMID- 10933348
TI  - A comparison of short- and long-term outcomes for balloon angioplasty and
      coronary stent placement.
AB  - OBJECTIVES: We sought to compare patient outcomes for coronary stent placement
      and balloon angioplasty. BACKGROUND: Since 1994, the number of patients treated
      only with balloon angioplasty has decreased nationally, whereas the use of
      coronary stents as an alternative has grown tremendously. The objectives of this
      study were to compare short- and long-term survival and subsequent
      revascularization rates for patients undergoing single-vessel balloon angioplasty
      and coronary stent placement. METHODS: New York's Coronary Angioplasty Registry
      was used to identify New York patients undergoing either balloon angioplasty or
      stent placement between July 1, 1994, and December 31, 1996. Statistical models
      were used to compare risk-adjusted short- and long-term survival and subsequent
      coronary artery bypass graft surgery (CABG) and percutaneous coronary
      interventions (PCIs). RESULTS: No significant differences were found in adjusted
      in-patient mortality, but patients who had balloon angioplasty were, on average,
      1.36 times more likely to have died at any time during the two-year period after
      the index procedure (p = 0.003). The adjusted in-patient CABG rate was
      significantly higher for balloon angioplasty (2.72% vs. 1.66%, p<0.0001), and the
      adjusted two-year CABG rate was also significantly higher for balloon angioplasty
      (10.81% vs. 7.25%, p<0.001). The adjusted two-year rate for subsequent PCIs was
      also significantly higher for balloon angioplasty (19.6% vs. 14.3%, p<0.0001).
      Although measures were taken to eliminate or minimize the effect of selection
      bias, it should be noted that patients with stents were healthier at hospital
      admission than patients who had balloon angioplasty. CONCLUSIONS: Stent placement
      is associated with significantly lower risk-adjusted long-term mortality, CABG
      and subsequent PCI rates, as compared with balloon angioplasty.

PMID- 10933349
TI  - The French Randomized Optimal Stenting Trial: a prospective evaluation of
      provisional stenting guided by coronary velocity reserve and quantitative
      coronary angiography. F.R.O.S.T. Study Group.
AB  - OBJECTIVES: We sought to make a prospective comparison of systematic stenting
      with provisional stenting guided by Doppler measurements of coronary velocity
      reserve and quantitative coronary angiography. BACKGROUND: Despite the increasing
      use of stents during percutaneous transluminal coronary angioplasty, it is
      unclear whether systematic stenting is superior to a strategy of provisional
      stenting in which stents are placed only in patients with unsatisfactory results
      or as a bail-out procedure. METHODS: Two hundred fifty-one patients undergoing
      elective coronary angioplasty were randomly assigned either to provisional
      stenting (group 1, in which stenting was performed if postangioplasty coronary
      velocity reserve was <2.2 and/or residual stenosis > or =35% or as bail-out) or
      to systematic stenting (group 2). The primary end point was the six-month
      angiographic minimal lumen diameter (MLD). Major adverse cardiac events were
      secondary end points (death, acute myocardial infarction and target lesion
      revascularization). RESULTS: Stenting was performed in 48.4% of patients in group
      1 and 100% of patients in group 2 (p<0.01). Six months after angioplasty, the MLD
      did not differ between groups (1.90+/-0.79 mm vs. 1.99+/-0.70 mm, p = 0.39), as
      was the rate of binary restenosis (27.1% vs. 21.4%, p = 0.37). Among patients
      with restenosis, 13/32 (40.6%) in group 1 but 100% (25/25) in group 2 had in
      stent restenosis (p<0.01). Target lesion revascularization (15.1% vs. 14.4% in
      groups 1 and 2 respectively, p = 0.89) and major adverse cardiac events (15.1%
      vs. 16.0%, p = 0.85) were not significantly different. CONCLUSIONS: Systematic
      stenting does not provide superior angiographic results at six months as compared
      with provisional stenting.

PMID- 10933351
TI  - Enhanced peripheral vasodilation in humans after a fatty meal.
AB  - OBJECTIVES: We sought to study the effects of a fatty meal on vascular
      reactivity, including endothelial function and maximal vasodilation. BACKGROUND:
      Recent reports regarding the physiological changes in peripheral vasculature
      after eating a fatty meal have been controversial. METHODS: Twelve volunteers
      were studied before, 3 h after, and 6 h after a high-fat meal (1030 kcal, 61 g
      fat) rich in saturated fatty acids, and 10 were restudied after a similar meal
      rich in monounsaturated fatty acids. Endothelial function was assessed as flow
      mediated dilatation (FMD) in the brachial artery using ultrasound. Resting and
      postischemic forearm blood flow (FBF) were recorded using venous occlusion strain
      gauge plethysmography, before, and every 10 to 15 s after, 5 min upper arm
      ischemia. RESULTS: Brachial artery basal diameter, resting FBF and postischemic
      hyperemia increased after high-fat meals (all p<0.001), whereas FMD did not
      change. The increase in resting FBF correlated with increases in postprandial
      insulin (r = 0.80, p<0.002) and triglyceride (r = 0.77, p<0.005) levels.
      CONCLUSIONS: We concluded that eating a fatty meal induces vasodilation and
      increases resting and stimulated FBF and that these observations are probably
      mediated by postprandial changes in insulin and/or triglyceride levels. The
      metabolic changes that occur after meals are not associated with impaired
      endothelial nitric oxide release in the conduit arteries.

PMID- 10933350
TI  - Atorvastatin but not L-arginine improves endothelial function in type I diabetes
      mellitus: a double-blind study.
AB  - OBJECTIVES: We sought to determine the effects of oral L-arginine and the
      hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial
      function in young patients with type I diabetes mellitus (DM). BACKGROUND:
      Endothelial dysfunction, a key early event in atherosclerosis, occurs in young
      patients with type I DM, and its reversal may benefit the progression of vascular
      disease. Cholesterol reduction in L-arginine improve endothelial function in
      nondiabetic subjects, but their effect in patients with type I DM is unknown.
      METHODS: In a double-blind, 2x2 factorial study, we investigated the effect of L
      arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery
      vascular function in 84 normocholesterolemic young adults (mean+/-SD: age 34
      years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96+/-0.89
      mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated
      dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN)
      were assessed noninvasively using high resolution ultrasound at baseline and
      after six weeks of treatment. RESULTS: Atorvastatin resulted in a 48+/-10%
      decrease in serum LDL cholesterol levels, whereas L-arginine levels increased by
      247+/-141% after L-arginine therapy. By analysis of covariance, treatment with
      atorvastatin resulted in a significant increase in FMD (p = 0.018. L-Arginine
      therapy had no significant effect on endothelial function, and there was no
      significant change in dilation to GTN after either intervention. CONCLUSIONS: In
      young patients with type I DM, improvement in endothelial dysfunction can be
      demonstrated after just six weeks of treatment with atorvastatin. In contrast to
      studies of hypercholesterolemia, however, L-arginine had no benefit. Treatment
      with atorvastatin at an early stage may have an impact on the progression of
      atherosclerosis in these high risk patients.

PMID- 10933352
TI  - Plasma concentration of soluble vascular cell adhesion molecule-1 and subsequent
      cardiovascular risk.
AB  - OBJECTIVES: The purpose of this study was to evaluate whether soluble vascular
      cell adhesion molecule-1 (sVCAM-1) is a marker for increased cardiovascular risk.
      BACKGROUND: Soluble forms of cellular adhesion molecules (CAMs) may be useful
      markers of endothelial activation and local or systemic inflammation. Recent
      studies indicate that plasma concentration of soluble intercellular adhesion
      molecule-1 (sICAM-1) is elevated many years before a first myocardial infarction
      (MI) occurs. However, only a few prospective studies have evaluated whether sVCAM
      1 is also a marker for increased cardiovascular risk. METHODS: Baseline plasma
      samples were obtained prospectively from 14,916 healthy participants in the
      Physicians' Health Study. In a nested, case-control study design, the plasma
      concentration of sVCAM-1 was measured in 474 men with confirmed MI during the
      nine-year follow-up period, and in an equal number of control subjects who
      remained free of reported cardiovascular disease and who were matched for age,
      smoking status and length of follow-up. RESULTS: No significant difference in the
      median baseline sVCAM-1 concentration was found between case and control subjects
      (638 vs. 634 ng/ml; p = NS). Cardiovascular risk was similar between patients
      with sVCAM-1 levels in the highest quartile and those in the lowest quartile, in
      both crude (relative risk [RR] 1.28, 95% confidence interval [CI] 0.85 to 1.92)
      and adjusted (RR 1.17, 95% CI 0.71 to 1.91) matched-pairs analyses. CONCLUSIONS:
      In contrast to previous data on sICAM-1, we found no evidence of an association
      between sVCAM-1 levels and the risk of future MI in a large cohort of apparently
      healthy men. These data suggest important pathophysiologic differences between
      sVCAM-1 and sICAM-1 in the genesis of atherothrombosis.

PMID- 10933353
TI  - Simvastatin inhibits the monocyte expression of proinflammatory cytokines in
      patients with hypercholesterolemia.
AB  - OBJECTIVE: The purpose of this study was to assess if simvastatin has an anti
      inflammatory activity in patients with hypercholesterolemia. BACKGROUND:
      Simvastatin, an inhibitor of 3-hydroxy-methyl-glutaryl coenzyme A (HMG-CoA)
      reductase, reduced cardiovascular events in patients with myocardial infarction
      and hypercholesterolemia. METHODS: Sixteen patients with polygenic
      hypercholesterolemia were randomly allocated to diet (n = 8) or diet plus 20
      mg/day simvastatin (n = 8) for eight weeks. Before and at the end of treatment
      period, lipid profile and monocyte expression of tumor necrosis factor-alpha
      (TNF) and interleukin-1beta (IL-1beta) were measured. RESULTS: At baseline no
      difference in lipid profile and monocyte expression of TNF and IL-1beta were
      observed between the two groups. In patients allocated to diet alone, no change
      in lipid profile and monocyte expression of TNF and IL-1beta was seen. In
      patients with diet plus simvastatin, significant decreases of total cholesterol (
      27%, p<0.02), low density lipoprotein-cholesterol (-33%, p<0.02), and monocyte
      expression of TNF (-49%, p<0.02) and IL-1beta (-35%, p<0.02) were observed. At
      the end of treatment period, patients treated with simvastatin had lower
      cholesterol and monocyte TNF and IL-1beta than did patients assigned to diet
      alone. CONCLUSION: This study suggests that simvastatin possesses anti
      inflammatory activity via the inhibition of pro-inflammatory cytokines TNF and IL
      1beta expressed by monocytes.

PMID- 10933354
TI  - Diffuse intimal thickening of coronary arteries in patients with coronary spastic
      angina.
AB  - OBJECTIVES: The purpose of this study was to evaluate the extent of
      atherosclerotic changes in angiographically normal coronary arteries using
      intravascular ultrasound (IVUS) technique in patients with coronary spastic
      angina. BACKGROUND: Nitric oxide activity was shown to be decreased in coronary
      arteries of patients with coronary spastic angina (CSA). Decrease in nitric oxide
      causes arterial intimal hyperplasia or thickening. However, it remains unclear
      whether intimal thickening is diffusely present in coronary arteries of patients
      with CSA. METHODS: The IVUS study was performed in 26 patients with CSA and with
      normal coronary angiograms and in 31 control subjects in whom age and gender was
      matched with those in patients with CSA. RESULTS: Compared with control subjects,
      patients with CSA had significantly larger percent intima + media area (%I + M
      area), intima + media area and maximal intima + media thickness in all of
      proximal, middle and distal segments (p<0.01, respectively). Lumen area was
      comparable between these groups. The presence of spasm was the most powerful
      independent predictor of increase in percent intima + media area, in multiple
      regression analysis with the traditional risk factors as covariates. CONCLUSIONS:
      Intimal thickening existed entirely in a coronary artery in patients with CSA and
      with normal angiograms, independently of other traditional risk factors. The
      diffuse intimal thickening in the spasm coronary arteries is intimately related
      with coronary spasm.

PMID- 10933355
TI  - Randomized, placebo-controlled trial of the angiotensin-converting enzyme
      inhibitor, ramipril, in patients with coronary or other occlusive arterial
      disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with
      Ramipril.
AB  - OBJECTIVES: The primary objective of this study was to investigate the effects of
      the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid
      atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular
      disease. BACKGROUND: Angiotensin-converting enzyme inhibitors have been shown to
      reduce the risk of coronary events in various patient groups and to prevent the
      development of atherosclerosis in animal models. It has been hypothesized that
      the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on
      atherosclerosis. METHODS: Six hundred seventeen patients were randomized in equal
      proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and
      four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left
      ventricular mass was assessed by M-mode echocardiography. RESULTS: Blood pressure
      (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the
      ramipril group compared with the placebo group (p<0.001). There was no difference
      between groups in the changes in common carotid artery wall thickness (p = 0.58)
      or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8
      g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04).
      CONCLUSIONS: The results provide no support for the hypothesis that reduced
      atherosclerosis is responsible for the beneficial effects of ACE inhibitors on
      major coronary events. It is more likely that the benefits are due to lower BP,
      reduced left ventricular mass or other factors such as reversal of endothelial
      dysfunction.

PMID- 10933357
TI  - Acute effects of urinary bladder distention on the coronary circulation in
      patients with early atherosclerosis.
AB  - OBJECTIVES: We sought to examine whether distention of the urinary bladder, a
      physiologic stimulus, could induce impaired coronary circulation in patients with
      early atherosclerosis. BACKGROUND: Distention of the urinary bladder reflexively
      causes an increase in sympathetic activity. The effect of such distention on the
      coronary circulation in patients with early atherosclerosis remains unknown.
      METHODS: To assess the effect of bladder distention on coronary dynamic forces,
      epicardial and microvascular responses were measured with an intracoronary
      Doppler flow wire in 40 patients with early atherosclerosis (<50% diameter
      stenosis). Patients were randomized into two groups according to whether they did
      not (group 1, n = 20) or did have (group 2, n = 20) pretreatment with an alpha1
      adrenergic receptor blocker (oral doxazosin, 2 mg). Coronary flow velocity was
      monitored by quantitative coronary angiography at baseline, during urinary
      bladder distention and after intracoronary nitroglycerin injection. RESULTS:
      Bladder distention significantly decreased the coronary diameter in the stenotic
      segments (p<0.001), decreased coronary blood flow (p<0.001) and increased
      coronary resistance (p<0.001), as compared with baseline values, in group 1
      patients. In group 2 patients with bladder distention, the angiographic variables
      did not show significant changes, as compared with baseline values. No
      significant differences were noted between the groups in the responses of the
      angiographic variables after nitroglycerin administration. CONCLUSIONS: The
      present study shows, for the first time, that urinary bladder distention caused
      vasoconstriction of coronary conduit and resistance vessels involved mechanisms
      related to alpha1 adrenoceptors. Pretreated administration of doxazosin reversed
      the changes toward baseline. Vasoconstriction during bladder distention can be
      relieved after nitroglycerin administration, suggesting an unchanged
      responsiveness of vascular smooth muscle cells to such distention.

PMID- 10933356
TI  - Regional diastolic function by pulsed Doppler myocardial mapping for the
      detection of left ventricular ischemia during pharmacologic stress testing: a
      comparison with stress echocardiography and perfusion scintigraphy.
AB  - OBJECTIVES: We evaluated regional diastolic function by pulsed Doppler myocardial
      mapping for the detection of left ventricular ischemia during pharmacologic
      stress testing. BACKGROUND: Evaluation and quantification of diastolic myocardial
      function remain a challenge for imaging techniques in stress tests. METHODS: A
      prospective study compared the detection of coronary artery stenosis: 1) by
      pulsed Doppler myocardial mapping, 2) by two-dimensional echocardiographic
      dobutamine stress test, and 3) by perfusion scintigraphy in 64 patients using
      coronary angiography for reference. An age matched subgroup of 10 patients with
      normal angiograms and two-dimensional echocardiographic stress test served as
      control group. Peak myocardial contraction velocity (Vc) and lengthening rate
      during early diastolic left ventricular (LV) filling (VE) were measured in 12 LV
      segments from three apical views. RESULTS: In controls, myocardial velocities
      increased during stress by > or =3.6 cm/s (p < 0.001). In LV segments depending
      on a stenosed artery (n = 70), VE decreased by > or =1 cm/s and, thus, was
      different from control segments (n = 112, p < 0.001) and from scar segments (n =
      13, p < 0.01), whereas the change of Vc was similar to that in scar segments. A
      stress induced 2 cm/s reduction of VE discerned the best diagnostic accuracy
      (sensitivity 84%, specificity 93%) in comparison with two-dimensional
      echocardiography (78% and 71%) and perfusion scintigraphy (61% and 86%). Using
      receiver operating curves at incremental levels of luminal narrowing, these
      relations persisted. CONCLUSIONS: Quantification of diastolic myocardial function
      by pulsed Doppler myocardial mapping during dobutamine stress test was shown to
      be a feasible, accurate, reproducible, noninvasive technique that should be
      considered to be a sensitive alternative to the present echocardiographic and
      scintigraphic imaging techniques for stress tests.

PMID- 10933358
TI  - Prevalence and correlates of aortic regurgitation in American Indians: the Strong
      Heart Study.
AB  - OBJECTIVES: We sought to determine the prevalence and correlates of aortic
      regurgitation (AR) in a population-based sample group. BACKGROUND: Concern over
      induction of AR by weight loss medication highlights the importance of assessing
      the prevalence and correlates of AR in unselected patient groups. METHODS: Aortic
      regurgitation was assessed by color flow Doppler echocardiography in 3,501
      American Indian participants age 47 to 81 years during the second Strong Heart
      Study. RESULTS: Mild (1+) AR was present in 7.3%, 2+ AR in 2.4% and 3+ to 4+ AR
      in 0.3% of participants, more frequently in those > or =60 years old than in
      those <60 years old (14.4% vs. 5.8%, p<0.001); AR was unrelated to gender.
      Compared with participants without AR, those with mild AR had a lower body mass
      index (p<0.004) and higher systolic pressure (p<0.003). Participants with AR had
      larger aortic root diameters (3.6+/-0.4 vs. 3.4+/-0.4 cm, p<0.001), higher
      creatinine levels (1.3+/-1.3 vs. 1.0+/-1.0 mg/dl, p<0.001) and higher urine
      albumin/creatinine levels (3.6+/-2.3 vs. 3.3+/-2.0 log, p<0.001), as well as
      higher prevalences of aortic stenosis (AS) or mitral stenosis (MS) (p<0.001).
      Regression analysis showed that AR was independently related to older age and
      larger aortic roots (p<0.0001), AS and absence of diabetes (p = 0.002), MS (p =
      0.003) and higher log urine albumin/creatinine (p = 0.005). CONCLUSIONS: Aortic
      regurgitation occurred in 10% of a sample group of middle-aged to older adults
      and was related to older age, larger aortic root diameter, aortic and mitral
      stenosis and albuminuria. There was no association of AR with being overweight
      and a negative association of AR with diabetes.

PMID- 10933360
TI  - Quantification of tricuspid regurgitation by measuring the width of the vena
      contracta with Doppler color flow imaging: a clinical study.
AB  - OBJECTIVE: We sought to evaluate the vena contracta width (VCW) measured using
      color Doppler as an index of severity of tricuspid regurgitation (TR).
      BACKGROUND: The VCW is a reliable measure of mitral and aortic regurgitation, but
      its value in measuring TR is uncertain. METHODS: In 71 consecutive patients with
      TR, the VCW was prospectively measured using color Doppler and compared with the
      results of the flow convergence method and hepatic venous flow, and its
      diagnostic value for severe TR was assessed. RESULTS: The VCW was 6.1+/-3.4 mm
      and was significantly higher in patients with, than those without, severe TR
      (9.6+/-2.9 vs. 4.2 +/- 1.6 mm, p<0.0001). The VCW correlated well with the
      effective regurgitant orifice (ERO) by the flow convergence method (r = 0.90, SEE
      = 0.17 cm2, p<0.0001), even when restricted to patients with eccentric jets (r =
      0.93, p < 0.0001). The VCW also showed significant correlations with hepatic
      venous flow (r = 0.79, p < 0.0001), regurgitant volume (r = 0.77, p<0.0001) and
      right atrial area (r = 0.46, p< 0.0001). A VCW > or =6.5 mm identified severe TR
      with 88.5% sensitivity and 93.3% specificity. In comparison with jet area or
      jet/right atrial area ratio, the VCW showed better correlations with ERO (both
      p<0.01) and a larger area under the receiver operating characteristic curve (0.98
      vs. 0.88 and 0.85, both p<0.02) for the diagnosis of severe TR. CONCLUSIONS: The
      VCW measured by color Doppler correlates closely with severity of TR. This
      quantitative method is simple, provides a high diagnostic value (superior to that
      of jet size) for severe TR and represents a useful tool for comprehensive,
      noninvasive quantitation of TR.

PMID- 10933359
TI  - Surgical left atrial appendage ligation is frequently incomplete: a
      transesophageal echocardiograhic study.
AB  - OBJECTIVES: This study sought to determine the incidence of incomplete ligation
      of the left atrial appendage (LAA) during mitral valve surgery. BACKGROUND:
      Ligation of the LAA to prevent future thromboembolic events is commonly performed
      during mitral surgery. However, success in completely excluding the appendage
      from the circulation has never been systematically assessed. METHODS: Using
      transesophageal Doppler echocardiography, we studied 50 patients who underwent
      mitral valve surgery and ligation of the LAA. Thirty patients were studied
      immediately postoperative, and 20 patients were studied 6 days to 13 years after
      surgery. Incomplete ligation was detected by demonstrating a color jet traversing
      the separation between the left atrial body and appendage. RESULTS:
      Transesophageal echocardiography detected incomplete LAA ligation in 18 of 50
      (36%) patients. The incidence of incomplete ligation was not significantly
      different between patients studied immediately postoperative and patients studied
      at various times after surgery. Type of mitral surgery (repair vs. replacement),
      operative approach (sternotomy vs. port access), left atrial size or degree of
      mitral regurgitation did not significantly correlate with the incidence of
      incomplete appendage ligation. However, the power to detect a significant
      difference in left atrial size was only 64%. Spontaneous echo contrast or
      thrombus was identified within appendages in 9 of 18 (50%) patients with
      incomplete ligation, while 4 of these 18 (22%) patients had thromboembolic
      events. CONCLUSIONS: Surgical LAA ligation is frequently incomplete. The similar
      incidence of incomplete ligation detected immediately postoperative and at
      various times thereafter suggest that this results from an intraoperative
      phenomenon rather than from gradual dehiscence of sutures over years. The
      incidence of incomplete left atrial ligation was unrelated to type of surgery,
      surgical approach, left atrial size or degree of mitral regurgitation. Residual
      communication between the incompletely ligated appendage and the left atrial body
      may produce a milieu of stagnant blood flow within the appendage and be a
      potential mechanism for embolic events.

PMID- 10933361
TI  - The clinical, cardiac, renal, arterial and neurohormonal effects of omapatrilat,
      a vasopeptidase inhibitor, in patients with chronic heart failure.
AB  - OBJECTIVES: We sought to examine the effects of long-term vasopeptidase
      inhibition in patients with heart failure. BACKGROUND: The long-term effects of
      omapatrilat, an agent that inhibits both neutral endopeptidase and angiotensin
      converting enzyme, on clinical status, neurohormonal indexes and left ventricular
      function in patients with chronic heart failure (CHF) have not been previously
      documented. METHODS: Forty-eight patients in New York Heart Association
      functional class II or III, with left ventricular ejection fraction (LVEF)< or
      =40% and in sinus rhythm were randomized to a dose-ranging pilot study of
      omapatrilat for 12 weeks. Measurements were performed at baseline and 12 weeks.
      RESULTS: There was an improvement in functional status, as reported by the
      patient (p<0.001) and physician (p<0.001) at 12 weeks. Dose-dependent
      improvements in LVEF (p<0.001) and LV end-systolic wall stress (sigma) (p<0.05)
      were seen, together with a reduction in systolic blood pressure (p<0.05). There
      was evidence of a natriuretic effect (p<0.001), and total blood volume decreased
      (p<0.05). Omapatrilat induced an increase in postdose plasma atrial natriuretic
      peptide levels (p<0.01) in the high dose groups, with a reduction in predose
      plasma brain natriuretic peptide (p<0.001) and epinephrine (p<0.01) levels after
      12 weeks of therapy. Omapatrilat was well tolerated. CONCLUSIONS: The sustained
      hemodynamic, neurohumoral and renal effects of omapatrilat, together with
      improved functional status, suggest that vasopeptidase inhibition has potential
      as a new therapeutic modality for the treatment of CHF.

PMID- 10933362
TI  - High dose angiotensin-converting enzyme inhibition prevents fluid volume
      expansion in heart transplant recipients.
AB  - OBJECTIVES: We sought to test the hypothesis that plasma volume (PV) expansion in
      heart transplant recipients (HTRs) is caused by failure to reflexively suppress
      the renin-angiotensin-aldosterone (RAA) axis. BACKGROUND: Extracellular fluid
      volume expansion occurs in clinically stable HTRs who become hypertensive. We
      have previously demonstrated that the RAA axis is not reflexively suppressed by a
      hypervolemic stimulus in HTRs. METHODS: Plasma volume and fluid regulatory
      hormones were measured in eight HTRs (57+/-6 years old) both before and after
      treatment with captopril (225 mg/day). Antihypertensive and diuretic agents were
      discontinued 10 days before. The HTRs were admitted to the Clinical Research
      Center (CRC), and, after three days of a constant diet containing 87 mEq/day of
      Na+, PV was measured by using the modified Evans blue dye dilution technique.
      After approximately four months (16+/-5 weeks), the same HTRs again discontinued
      all antihypertensive and diuretic agents; they were progressed to a captopril
      dose of 75 mg three times per day over 14 days, and the CRC protocol was
      repeated. RESULTS: Captopril pharmacologically suppressed (p<0.05) supine rest
      levels of angiotensin II (-65%) and aldosterone (-75%). The reductions in
      vasopressin and atrial natriuretic peptide levels after captopril did not reach
      statistical significance. The PV, normalized for body weight (ml/kg), was
      significantly reduced by 12% when the HTRs received captopril. CONCLUSIONS:
      Extracellular fluid volume is expanded (12%) in clinically stable HTRs who become
      hypertensive. Pharmacologic suppression of the RAA axis with high-dose captopril
      (225 mg/day) returned HTRs to a normovolemic state. These findings indicate that
      fluid retention is partly engendered by a failure to reflexively suppress the RAA
      axis when HTRs become hypervolemic.

PMID- 10933363
TI  - Long-term follow-up of 34 adults with isolated left ventricular noncompaction: a
      distinct cardiomyopathy with poor prognosis.
AB  - OBJECTIVES: We sought to describe characteristics and outcome in adults with
      isolated ventricular noncompaction (IVNC). BACKGROUND: Isolated ventricular
      noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of
      compaction of the loose interwoven meshwork. Knowledge regarding diagnosis,
      morbidity and prognosis is limited. METHODS: Echocardiographic criteria for IVNC
      include-in the absence of significant heart lesions-segmental thickening of the
      left ventricular myocardial wall consisting of two layers: a thin, compacted
      epicardial and an extremely thickened endocardial layer with prominent
      trabeculations and deep recesses. Thirty-four adults (age >16 years, 25 men)
      fulfilled the diagnostic criteria and were followed prospectively. RESULTS: At
      diagnosis, mean age was 42 + 17 years, and 12 patients (35%) were in New York
      Heart Association class III/IV. Left ventricular end-diastolic diameter was 65 +
      12 mm and ejection fraction 33 + 13%. Apex and/or midventricular segments of both
      the inferior and lateral wall were involved in >80% of patients. Follow-up was 44
      + 40 months. Major complications were heart failure in 18 patients (53%),
      thromboembolic events in 8 patients (24%) and ventricular tachycardias in 14
      patients (41%). There were 12 deaths: sudden in six, end-stage heart failure in
      four and other causes in two patients. Four patients underwent heart
      transplantation. Automated cardioverter/defibrillators were implanted in four
      patients. CONCLUSIONS: Diagnosis of IVNC by echocardiography using strict
      criteria is feasible. Its mortality and morbidity are high, including heart
      failure, thrombo-embolic events and ventricular arrhythmias. Risk stratification
      includes heart failure therapy, oral anticoagulation, heart transplantation and
      implantation of an automated defibrillator/cardioverter. As IVNC is a distinct
      entity, its classification as a specific cardiomyopathy seems to be more
      appropriate.

PMID- 10933366
TI  - Left ventricular dysfunction predicted by early troponin I release after high
      dose chemotherapy.
AB  - OBJECTIVES: We investigated the role of cardiac troponin I (cTnI) in patients
      with aggressive malignancies treated with high-dose chemotherapy (HDC).
      BACKGROUND: High dose chemotherapy is potentially limited by cardiac toxicity.
      Considering the fact that cardiac dysfunction may become clinically evident weeks
      or months after HDC, the availability of an early marker of myocardial injury,
      able to predict late ventricular impairment, is a current need. METHODS: We
      measured, in 204 patients (45+/-10 years) affected by cancer resistant to
      conventional treatment, the cTnI plasma concentration after every single cycle of
      HDC. According to the cTnI value (< or = or >0.4 ng/ml), patients were divided
      into a troponin positive (cTnI+, n = 65) and a troponin negative (cTnI-, n = 139)
      group. All patients underwent echocardiographic examination during the following
      seven months. RESULTS: In the cTnI- group, left ventricular ejection fraction
      (LVEF) progressively decreased after HDC, reaching a maximal reduction after
      three months; however, myocardial depression was transient and no longer
      detectable at later follow-up. By contrast, in the cTnI+ group LVEF reduction was
      more marked and still evident at the end of the follow-up. In cTnI+ patients, a
      close relationship between the short-term cTnI increment and the greatest LVEF
      reduction was found (r = -0.87, p<0.0001). CONCLUSIONS: The elevation of cTnI in
      patients undergoing HDC for aggressive malignancies accurately predicts the
      development of future LVEF depression. In this setting, cTnI can be considered a
      sensitive and reliable marker of acute minor myocardial damage with relevant
      clinical and prognostic implications.

PMID- 10933365
TI  - Plasma atherogenic markers in congestive heart failure and posttransplant (heart)
      patients.
AB  - OBJECTIVES: We hypothesized that plasma factors important for the development of
      atherosclerosis play a major role in the occurrence of cardiac allograft
      vasculopathy (CAV). BACKGROUND: Cardiac allograft vasculopathy is a major cause
      of death among heart transplant recipients, has a poorly understood pathogenesis
      and has similarities to atherosclerotic coronary disease. METHODS: The study
      population consisted of 93 postcardiac transplant recipients. Thirty-one patients
      with congestive heart failure (CHF) and 18 healthy individuals served as control
      subjects. Posttransplant coronary anatomy was evaluated by angiography and
      intravascular ultrasound. Laboratory analyses of lipids, homocysteine, vitamin
      B12 and folate, fibrinogen, von Willebrand factor antigen (vWFAg) and renin were
      obtained on all participants. RESULTS: Posttransplant patients were found to have
      elevated serum triglycerides, total cholesterol/ high-density lipoprotein
      cholesterol ratio, lipoprotein (a), homocysteine, vWFAg, fibrinogen and renin and
      lower high-density lipoprotein cholesterol. Most of these laboratory atherogenic
      factors were also elevated to a similar degree in the CHF control population.
      Although most atherogenic markers were elevated, there was little correlation
      with CAV severity. Cardiac allograft vasculopathy severity varied with time after
      transplantation, 3-hydroxy-methyl-glutaryl-coenzyme A reductase inhibitor use and
      prior cytomegalovirus infection. Even within the normal range, lower RBC folate
      levels were associated with increased severity of CAV. CONCLUSIONS: The
      posttransplant course is associated with increased clinical and laboratory
      atherogenic factors, some of which likely contribute to the severity of coronary
      vasculopathy. Compared with normal control subjects, many of these markers are
      already increased in pretransplant CHF patients with or without occlusive
      coronary artery disease.

PMID- 10933367
TI  - The relationship of the erythrocyte sedimentation rate to inflammatory cytokines
      and survival in patients with chronic heart failure treated with angiotensin
      converting enzyme inhibitors.
AB  - OBJECTIVES: The object of the study was to assess the relationship between
      erythrocyte sedimentation rate (ESR) and inflammatory cytokine production in
      chronic heart failure (CHF). Our findings lead us to re-evaluate the prognostic
      value of the ESR in assessing patients with CHF. BACKGROUND: The search for
      simple prognostic markers in CHF that can be assessed anywhere at low cost is
      important. Increases in ESR are related to the acute phase response in states of
      inflammation and infection. METHODS: Initially, we studied ESR in relation to
      plasma levels of inflammatory cytokines in 58 CHF patients. The findings prompted
      us to analyze the mortality predictive power of ESR compared with established
      risk factors in these patients and (retrospectively) in a second group of 101
      clinically stable CHF patients who had ESR measured. RESULTS: In all 159 CHF
      patients (age 62+/-2 years, New York Heart Association [NYHA] class 2.7+/-0.1),
      ESR ranged from 1 to 96 mm/h (median 14 mm/h). The ESR was correlated with tumor
      necrosis factor (TNF)-alpha (r = 0.31, p<0.05), soluble TNF receptor-1 (r = 0.48,
      p<0.0005), soluble TNF receptor-2 (r = 0.39, p<0.005) and interleukin 6 (r =
      0.45, p<0.005) levels. High ESR levels indicated a poor prognosis (p<0.0001), and
      this was independent of age, NYHA class, ejection fraction and peak oxygen
      consumption (p < 0.005). Patients with ESR above median (> or =15 mm/h) compared
      with patients with ESR <15 mm/h had an impaired survival (hazard ratio 2.62, 95%
      confidence interval 1.58-4.36, p<0.0001). CONCLUSIONS: Our study demonstrates
      that in CHF a high ESR is an unfavorable prognostic sign, independent of
      patients' symptomatology and ventricular function. These results are in
      diametrical contrast to previous results. This may reflect a change in the
      underlying pathophysiology due to today's treatment with angiotensin-converting
      enzyme inhibitors.

PMID- 10933364
TI  - Low-dose enoximone improves exercise capacity in chronic heart failure. Enoximone
      Study Group.
AB  - OBJECTIVES: This study was designed to evaluate the effects of low-dose enoximone
      on exercise capacity. BACKGROUND: At higher doses the phosphodiesterase
      inhibitor, enoximone, has been shown to increase exercise capacity and decrease
      symptoms in heart failure patients but also to increase mortality. The effects of
      lower doses of enoximone on exercise capacity and adverse events have not been
      evaluated. METHODS: This is a prospective, double-blind, placebo-controlled,
      multicenter trial (nine U.S. centers) conducted in 105 patients with New York
      Heart Association class II to III, ischemic or nonischemic chronic heart failure
      (CHF). Patients were randomized to placebo or enoximone at 25 or 50 mg orally
      three times a day. Treadmill maximal exercise testing was done at baseline and
      after 4, 8 and 12 weeks of treatment, using a modified Naughton protocol.
      Patients were also evaluated for changes in quality of life and for increased
      arrhythmias by Holter monitoring. RESULTS: By the protocol-specified method of
      statistical analysis (the last observation carried-forward method), enoximone at
      50 mg three times a day improved exercise capacity by 117 s at 12 weeks (p =
      0.003). Enoximone at 25 mg three times a day also improved exercise capacity at
      12 weeks by 115 s (p = 0.013). No increases in ventricular arrhythmias were
      noted. There were four deaths in the placebo group and 2 and 0 deaths in the
      enoximone 25 mg three times a day and enoximone 50 mg three times a day groups,
      respectively. Effects on degree of dyspnea and patient and physician assessments
      of clinical status favored the enoximone groups. CONCLUSIONS: Twelve weeks of
      treatment with low-dose enoximone improves exercise capacity in patients with
      CHF, without increasing adverse events.

PMID- 10933368
TI  - Estrogen is associated with improved survival in aging women with congestive
      heart failure: analysis of the vesnarinone studies.
AB  - OBJECTIVES: This study sought to evaluate the effects of postmenopausal estrogen
      use on mortality in aging women with congestive heart failure (CHF). BACKGROUND:
      The age-related increase in CHF mortality in women may be related to a menopause
      associated increased incidence of coronary artery disease. In addition to
      inhibiting coronary atherosclerosis, estrogen may also have protective effects on
      cardiac myocytes independent of the coronary vasculature. We hypothesized that
      estrogen use is associated with improved survival in elderly women with CHF.
      METHODS: Associations between survival, estrogen use and patient characteristics
      were assessed in 1,134 women who were at least 50 years of age, had CHF and left
      ventricular ejection fraction (EF) < or =30% and were enrolled in one of three
      clinical trials of vesnarinone. RESULTS: All-cause 12-month mortality was 15.0%
      among the 237 estrogen users versus 27.1% among the 897 estrogen nonusers (p =
      0.004 for unadjusted comparison of survival). Similar results were observed for
      cardiac mortality. Regression analysis demonstrated that estrogen use was
      independently associated with improved survival (relative risk of mortality =
      0.68, 95% confidence interval 0.48 to 0.96, p = 0.03). Advanced age, low EF, New
      York Heart Association class IV CHF, Caucasian race and abnormal serum
      creatinine, sodium, potassium and transaminase were independently associated with
      increased mortality. CONCLUSIONS: Estrogen use among older women with CHF is
      associated with decreased overall and cardiac mortality.

PMID- 10933369
TI  - Sarcolemmal Na+/H+ exchanger activity and expression in human ventricular
      myocardium.
AB  - OBJECTIVES: To determine sarcolemmal Na+/H+ exchanger (NHE) activity and
      expression in human ventricular myocardium. BACKGROUND: Although the sarcolemmal
      NHE has been implicated in various physiological and pathophysiological phenomena
      in animal studies, its activity and expression in human myocardium have not been
      studied. METHODS: Ventricular myocardium was obtained from unused donor hearts
      with acute myocardial dysfunction (n = 5) and recipient hearts with chronic end
      stage heart failure (n = 11) through a transplantation program. Intracellular pH
      (pHi) was monitored in enzymatically isolated single ventricular myocytes by
      microepifluorescence. As the index of sarcolemmal NHE activity, the rate of H+
      efflux at a pHi of 6.90 J(H6.9)) was determined after the induction of
      intracellular acidosis in bicarbonate-free medium. Na+/H+ exchanger isoform 1
      (NHE1) expression in ventricular myocardium was determined by immunoblot
      analysis. RESULTS: Human ventricular myocytes exhibited readily detectable
      sarcolemmal NHE activity after the induction of intracellular acidosis, and this
      activity was suppressed by the NHE1-selective inhibitor HOE-642 (cariporide) at 1
      micromol/L. Sarcolemmal NHE activity of myocytes was significantly greater in
      recipient hearts (JH6.9 = 1.95+/-0.18 mmol/L/min) than it was in unused donor
      hearts (J(H6.9 = 1.06+/-0.15 mmol/L/min). In contrast, NHE1 protein was expressed
      in similar abundance in ventricular myocardium from both recipient and unused
      donor hearts. CONCLUSIONS: Sarcolemmal NHE activity of human ventricular myocytes
      arises from the NHE1 isoform and is inhibited by HOE-642. Sarcolemmal NHE
      activity is significantly greater in recipient hearts with chronic end-stage
      heart failure than it is in unused donor hearts, and this difference is likely to
      arise from altered posttranslational regulation.

PMID- 10933370
TI  - Circadian rhythm and sudden death in heart failure: results from Prospective
      Randomized Amlodipine Survival Trial.
AB  - OBJECTIVE: The purpose of this study was to address the timing of sudden death in
      advanced heart failure patients. BACKGROUND: Sudden death is a catastrophic event
      in cardiovascular disease. It has a circadian pattern prominent in the early AM,
      which has been thought to be due to a surge of sympathetic stimulation. We
      postulated that the distribution of events in advanced heart failure, with
      chronic sympathetic activation, would be more uniform implicating other potential
      mechanisms. METHODS: We analyzed data from Prospective Randomized Amlodipine
      Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and
      1-h blocks for uniformity of distribution in the entire cohort, and in the
      prespecified ischemic and nonischemic stratum. Further analyses were undertaken
      in the treatment groups of amlodipine and placebo, and among those receiving
      background therapy of aspirin and warfarin. RESULTS: Sudden deaths in the overall
      cohort showed a nonuniform distribution with a PM peak but not an AM peak. The
      ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic
      stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or
      warfarin use altered the distribution. CONCLUSIONS: Sudden death in advanced
      heart failure did not show an AM peak, suggesting that circadian sympathetic
      activation did not strongly influence these events. The PM peak noted is likely
      complex in origin and was not affected by antiischemic or antithrombotic
      medications.

PMID- 10933371
TI  - Responses to constant work rate bicycle ergometry exercise in primary pulmonary
      hypertension: the effect of inhaled nitric oxide.
AB  - OBJECTIVES: The purpose of this study was to investigate the responses of
      patients with primary pulmonary hypertension (PPH) to constant work rate exercise
      and to examine the effect of nitric oxide (NO) inhalation. BACKGROUND: Maximal
      exercise tolerance is reduced in PPH, but gas exchange responses to constant work
      rate exercise have not been defined. We hypothesized that increased pulmonary
      vascular resistance in PPH would reduce the rate of rise of minute oxygen
      consumption in response to a given work rate. Because NO may lower pulmonary
      vascular pressures in PPH, we also postulated that inhaled NO might ameliorate
      gas exchange abnormalities. METHODS: Nine PPH patients and nine matched normal
      subjects performed 6-min duration constant work rate cycle ergometry exercise
      (33.9+/-13.4 W). Patients performed two experiments: breathing air and breathing
      air with NO (20 ppm). Preexercise right ventricular systolic pressure was
      assessed by Doppler echocardiography. Normal subjects performed the air
      experiment only. Gas exchange and heart rate responses were characterized by
      fitting monoexponential curves. RESULTS: In PPH patients, resting right
      ventricular systolic pressure fell after NO inhalation (from 83.8+/-16.9 to
      73.9+/-21.6 mm Hg, p<0.01, analysis of variance with Tukey correction), but not
      after breathing air alone (from 88.0+/-20.8 to 86.7+/-20.6 mm Hg, p = NS). Nitric
      oxide did not affect any of the gas exchange responses. Minute oxygen consumption
      was similar by the end of exercise in patients and normals, but increased more
      slowly in patients (mean response time [MRT]: air, 63.17+/-14.99 s; NO, 61.60+/
      15.45 s) than normals (MRT, 32.73+/-14.79, p<0.01, analysis of variance, Tukey
      test). Minute oxygen consumption kinetics during recovery were slower in patients
      (MRT air: 82.50+/-29.94 s; NO, 73.36+/-15.87 s) than in normals (MRT, 34.59+/
      7.11 s, p<0.01). Heart rate kinetics during exercise and recovery were
      significantly slower in patients than in normals. CONCLUSIONS: The cardiac output
      response is impaired in PPH. Nitric oxide lowered pulmonary artery pressure at
      rest, but failed to improve exercise gas exchange responses.

PMID- 10933372
TI  - Ventricular tachycardias above the initially programmed tachycardia detection
      interval in patients with implantable cardioverter-defibrillators: incidence,
      prediction and significance.
AB  - OBJECTIVES: This retrospective study was performed to provide data on ventricular
      tachycardias (VT) with a cycle length longer than the initially programmed
      tachycardia detection interval (TDI) in patients with implantable cardioverter
      defibrillators (ICDs). BACKGROUND: It has been clinical practice to program a
      safety margin of 30 to 60 ms between the slowest spontaneous or inducible VT and
      the TDI. METHODS: Baseline characteristics of 659 consecutive patients with ICDs
      were prospectively; follow-up information was retrospectively collected. RESULTS:
      During a mean follow-up of 31+/-23 months, 377 patients (57.2%) had at least one
      recurrent VT or ventricular fibrillation; 47 patients (7.1%) suffered 61 VTs
      above the TDI. The risk of a VT above the TDI ranged between 2.7% and 3.5% per
      year during the first four years after ICD implantation. The difference between
      the cycle length of the slowest VT before ICD implantation, spontaneous or
      induced, and the first VT above TDI was 108+/-58 ms. Fifty-four VTs (88.5%) above
      the TDI were associated with significant clinical symptoms (angina or palpitation
      63.9%, heart failure 6.6% and syncope 8.2%). Six patients (9.8%) had to be
      resuscitated. Kaplan-Meyer analysis identified New York Heart Association class
      II or III (p = 0.021), ejection fraction < 0.40 (p = 0.027), spontaneous
      (p<0.001) or inducible (p<0.001) monomorphic VTs and the use of class III
      antiarrhythmic drugs (amiodarone, p<0.001; sotalol, p = 0.004) as risk predictors
      of VTs above the TDI. The risk of recurrent VTs above TDI was 11.8%, 12.5% and
      26.6% during the first, second and third year after first VT above TDI,
      respectively. CONCLUSIONS: The risk of VTs above the TDI is significantly
      increased in some patients, and many VTs above TDI cause significant clinical
      symptoms. A larger safety margin between spontaneous or inducible VTs and the TDI
      seems to be necessary in selected patients. This is in conflict with an increased
      risk of inadequate episodes and demands highly specific and sensitive detection
      algorithms in these patients.

PMID- 10933373
TI  - Clusters of ventricular tachycardias signify impaired survival in patients with
      idiopathic dilated cardiomyopathy and implantable cardioverter defibrillators.
AB  - OBJECTIVES: This retrospective study was undertaken to provide data on
      occurrence, significance and therapy of ventricular tachyarrhythmia (VT) clusters
      (VTCs) in patients with dilated cardiomyopathy (DCM) and implantable cardioverter
      defibrillators (ICDs). BACKGROUND: Data on the clinical significance of VTCs are
      lacking in patients with DCM and ICDs. METHODS: Baseline characteristics of 106
      consecutive patients with DCM and ICDs were prospectively collected, and chart
      reviews and episode data retrospectively analyzed. A VTC was defined as > or =3
      sustained VTs/24 h. RESULTS: During a mean follow-up of 33+/-23 months, 73
      patients (68.9%) had recurrent VT or ventricular fibrillation (VF), 43 patients
      (40.6%) suffered only single VTs and 30 patients (28.3%) experienced 52 clusters
      of VTs. Actuarial survival free of VT or VF was 44.6%, 33.0% and 26.5%, and
      survival free of VTC was 77.3%, 72.2% and 67.1% after one, two and three years,
      respectively. Independent predictors of VT clusters were heart failure before ICD
      implantation (p = 0.033), presenting monomorphic VT (p = 0.044), EF <0.40 (p =
      0.014) and inducible mVT, especially with right bundle branch block and superior
      axis configuration (p<0.001). Survival free of recurrent VTCs was 50.8%, 38.1%
      and 19.0% after one, two and three years, respectively. Once a VTC had occurred,
      only 56.7%, 46.4%, 30.9% and 15.5% of patients survived and were not transplanted
      after one, two, three and four years, respectively. Survival was even more
      reduced if a VTC was associated with cardiac decompensation: 65.6% and 21.9%
      after one and two years, respectively. CONCLUSIONS: Despite antiarrhythmic
      intervention, clusters of VTs occur and recur frequently in patients with DCM.
      They signify impaired survival, especially if they are associated with cardiac
      decompensation, and may be a harbinger of progressive myocardial deterioration
      rather than a primarily arrhythmic problem. The benefit of ICD therapy may
      therefore be low in these patients.

PMID- 10933374
TI  - Diagnostic value of tachycardia features and pacing maneuvers during paroxysmal
      supraventricular tachycardia.
AB  - OBJECTIVES: The purpose of this prospective study was to quantitate the
      diagnostic value of several tachycardia features and pacing maneuvers in patients
      with paroxysmal supraventricular tachycardia (PSVT) in the electrophysiology
      laboratory. BACKGROUND: No study has prospectively compared the value of multiple
      diagnostic tools in a large group of patients with PSVT. METHODS: One hundred
      ninety-six consecutive patients who had 200 inducible sustained PSVTs during an
      electrophysiology procedure were included. The diagnostic values of four baseline
      electrophysiologic parameters, nine tachycardia features and five diagnostic
      pacing maneuvers were quantified. RESULTS: The only tachycardia characteristic
      that was diagnostic of atrioventricular (AV) nodal reentry was a septal
      ventriculoatrial (VA) time of <70 ms, and no pacing maneuver was diagnostic for
      AV nodal reentry. An increase in the VA interval with the development of a bundle
      branch block was the only tachycardia characteristic that was diagnostic for
      orthodromic tachycardia, but it occurred in only 7% of all tachycardias. An
      atrial-atrial-ventricular response upon cessation of ventricular overdrive pacing
      was diagnostic of atrial tachycardia, and this maneuver could be applied to 78%
      of all tachycardias. Burst ventricular pacing excluded atrial tachycardia when
      the tachycardia terminated without depolarization of the atrium, but the result
      could be obtained only in 27% of patients. CONCLUSIONS: This prospective study
      quantitates the diagnostic value of multiple observations and pacing maneuvers
      that are commonly used during PSVT in the electrophysiology laboratory. The
      findings demonstrate that diagnostic techniques rarely provide a diagnosis when
      used individually. Therefore, careful observations and multiple pacing maneuvers
      are often required for an accurate diagnosis during PSVT. The results of this
      study provide a useful reference with which new diagnostic techniques can be
      compared.

PMID- 10933375
TI  - Results of transvenous occlusion of secundum atrial septal defects with the
      fourth generation buttoned device: comparison with first, second and third
      generation devices. International Buttoned Device Trial Group.
AB  - OBJECTIVES: The purpose of this study was to assess safety and effectiveness of
      the fourth generation buttoned device in dosing atrial septal defects (ASDs) and
      to test the hypothesis that introduction of double button reduces unbuttoning
      rate without reducing effectiveness. BACKGROUND: Because of the high unbuttoning
      rate (7.2%) with first, second and third generation buttoned devices, the device
      was modified (fourth generation) so that there were two radiopaque spring buttons
      4 mm apart on the button loop attached to the occluder. METHODS: During a four
      year period ending in September 1997, 423 patients, ages 1.5 to 80 years (median
      16 years), underwent closure of ASD at 40 medical centers around the world.
      RESULTS: The ASD size varied between 5 and 30 mm (median 17 mm). The device size
      varied between 25 and 60 mm. Unbuttoning occurred in 4 (0.9%) of 423 patients.
      Effective occlusion, defined as no (n = 343) or trivial (n = 34) residual shunt
      on echo-Doppler studies performed within 24 h of the procedure, was demonstrated
      in 377 patients (90%). Thus, the unbuttoning rate (0.9 vs. 7.2%) decreased
      (p<0.01) while effective occlusion rate (90 vs. 92%) remained unchanged (p>0.1)
      with this device, compared with earlier generation devices. During follow-up from
      one month to five years (23+/-15 months), 21 (5%) of 417 patients required
      surgical (n = 12) or transcatheter (n = 9) reintervention, mostly to treat
      significant residual shunt. In the remaining patients there was gradual reduction
      and disappearance of the residual shunt. No wire integrity problems were
      observed. CONCLUSIONS: These data suggest that the fourth generation buttoned
      device is as effective as earlier generation devices, but without significant
      unbuttoning. Follow-up results remained good, with a reintervention-free rate of
      89% at five years.

PMID- 10933376
TI  - Atrioventricular septal defects diagnosed in fetal life: associated cardiac and
      extra-cardiac abnormalities and outcome.
AB  - OBJECTIVES: We sought to establish the outlook for fetuses diagnosed with
      atrioventricular septal defect (AVSD) prenatally and its relation to additional
      cardiac, extracardiac and chromosomal abnormalities. BACKGROUND: Prediction of
      likely outcome of AVSD presenting prenatally is complicated by the wide variation
      in associated features. METHODS: Computerized records from 14,726 pregnancies
      referred to a fetal cardiology center were reviewed retrospectively. Pathological
      reports, postnatal records, follow-up inquiries and review of echocardiographic
      video recordings supplemented analysis of the records for all those with AVSD.
      RESULTS: Atrioventricular septal defect was confirmed in 301 fetuses. Eighty-six
      (39%) of the 218 with known karyotype had trisomy 21, and 21/218 (10%) had other
      chromosome abnormalities. Right isomerism occurred in 37/301 (12%) fetuses, left
      isomerism in 62 (20%), mirror image atrial arrangement in 2 (1%), and 200 (67%)
      had usual arrangement. Atrioventricular septal defect occurred without any other
      intracardiac abnormality in 155 fetuses (51%). Extracardiac abnormalities and
      nonkaryotypic syndromes were evident in 40 fetuses (13%, confidence interval [CI]
      9.5-17.1%). Uncomplicated cardiac anatomy was significantly associated with the
      presence of karyotype abnormality (p < 0.0001). Parents opted for termination of
      pregnancy in 175/298 (58.5%). For the continuing pregnancies, Kaplan-Meier
      estimates for live birth, survival past the neonatal period and survival to three
      years were 82% (CI 75.3-88.9%), 55% (CI 46.0%-0/64.3%) and 38% (CI 27.1-48.6%),
      respectively. Fetal hydrops and earlier year of diagnosis were independent
      variables with adverse influence on survival. CONCLUSIONS: Despite some
      improvements in the outlook for AVSD diagnosed prenatally, the overall prognosis
      remains considerably poorer than that implied from surgical series. The detection
      of associated cardiac and extracardiac abnormalities is important in order to
      give the best indication of the likely outcome when counseling parents.

PMID- 10933377
TI  - P wave signal-averaged electrocardiogram as a new marker for atrial
      tachyarrhythmias in postoperative Fontan patients.
AB  - OBJECTIVES: This study was undertaken to determine the potential role of P wave
      signal-averaged electrocardiogram (PSAECG) for risk assessment of atrial
      tachyarrhythmias (ATs) in patients after Fontan operation. BACKGROUND: Onset of
      atrial flutter/fibrillation (AFF) in patients who have undergone Fontan operation
      for univentricular hearts constitutes an unfavorable clinical event associated
      with a high risk of cardiovascular complications. There is no data available on
      PSAECG in postoperative Fontan patients to predict potential susceptibility to
      ATs. METHODS: Twenty-four post-Fontan patients and 15 age-matched healthy
      subjects were prospectively studied with PSAECG, and the following measurements
      were made: filtered P wave duration (FPWD), P wave vector integrals (PINTs), root
      mean-square voltage for the initial 30 ms (RMSi30), and duration of persistent
      amplitude signals <4 microV from the beginning of the P wave (Di4). RESULTS: The
      FPWDs were significantly longer in the study group patients with ATs when
      compared with the study group patients without ATs (p<0.01) and compared with the
      controls (p < 0.001). An FPWD cut point of 135 ms resulted in a sensitivity of
      71% and a specificity of 81% in differentiating patients with ATs from patients
      without ATs among the postoperative Fontan patients. The PINT was significantly
      greater in Fontan patients with AFF and also without AFF when compared with
      controls (p<0.01, p<0.05, respectively). The RMSi30 and the Di4 were not
      significantly different between study and control groups. CONCLUSIONS: Signal
      averaged P wave duration is significantly prolonged in postoperative Fontan
      patients. A prolonged signal-averaged P wave duration may be an effective
      noninvasive marker to predict risk of development of ATs in this patient group.

PMID- 10933378
TI  - Cardiac beta-adrenoceptors in chronic uremia: studies in humans and rats.
AB  - OBJECTIVES: The purpose of this study was to elucidate whether cardiac beta
      adrenergic effects may be blunted in patients on maintenance hemodialysis (HD)
      and may help to explain autonomic dysfunction. BACKGROUND: Patients on HD often
      suffer from autonomic dysfunction. METHODS: We investigated the cardiovascular
      response of five HD patients (age: 46.1+/-7.9 years) and six healthy volunteers
      (age: 48.2+/-7.5 years) to isoprenaline, pirenzepine and phenylephrine. For
      analysis of underlying mechanisms of beta-adrenoceptor hyporesponsiveness, six
      week-old male Wistar rats were rendered uremic by 5/6-nephrectomy (n = 9; SNX)
      and were killed for removal of the heart after six to seven weeks. Sham-operated
      rats (n = 15) served as controls. RESULTS: In the patient study, isoprenaline
      (3.5, 7, 17, 35 ng/kg/min, i.v.) led to an increase in heart rate, and shortening
      of the heart rate corrected duration of the electromechanical systole (QS2c),
      both of which were significantly reduced in HD patients. Baroreflex sensitivity
      was significantly reduced in HD patients. The response to low parasympathomimetic
      doses of pirenzepine was unchanged. In the rat study, left ventricular strips
      were placed in an organ bath, electrically driven and exposed to isoprenaline
      (10(-11) to 10(-6) mol/liter). While pD2 values were unchanged, maximum effect at
      the highest concentration was significantly reduced in SNX rats. The response to
      carbachol was not altered, nor was the M2-cholinoceptor density. There was no
      difference in beta-adrenoceptor density, or in immunodetectable amount of Gs and
      Gi protein. Activation of adenylyl cyclase evoked by isoprenaline was
      significantly reduced in left ventricular membranes of SNX rats, whereas effects
      of 10 micromol/liter GTP, 10 mmol/liter NaF, 10 micromol/liter forskolin and 10
      mmol/liter Mn2+ were not altered. CONCLUSIONS: Cardiac beta-adrenergic responses
      are blunted in chronic uremia due to reduced isoprenaline-dependent activation of
      adenylyl cyclase. This might be caused by an "uncoupling" of the receptor or by
      an inhibition of the receptor by uremic toxins.

PMID- 10933379
TI  - Coronary collateral development during chronic ischemia: serial assessment using
      harmonic myocardial contrast echocardiography.
AB  - OBJECTIVES: We sought to characterize collateral development in an experimental
      model of chronic myocardial ischemia by using myocardial contrast
      echocardiography (MCE). BACKGROUND: Coronary collaterals maintain myocyte
      viability during myocardial ischemia. The natural history and determinants of
      collateral development are difficult to study serially in vivo. METHODS: The left
      anterior descending coronary artery (LAD) in nine dogs was encircled (day 0) with
      a hydraulic occluder and ameroid constrictor to enable reversible and gradual
      total LAD occlusion, respectively. Myocardial contrast echocardiography was
      performed using intravenous injection of perfluorocarbon gas-containing
      microbubbles during two-dimensional harmonic echocardiographic imaging.
      Myocardial contrast echocardiography images and radiolabeled microsphere flow
      measurements were obtained during transient LAD occlusion on day 0. Over the
      ensuing six weeks, MCE imaging was performed during LAD occlusion at 10-day
      intervals. RESULTS: Myocardial contrast echocardiography risk area size
      (expressed as a percent of the left ventricular short axis slice) decreased over
      the course of six weeks (32%+/-3% on day 0, 21% +/-3% at day 10, 5+/-3% at day
      20, 1%+/-1% at day 30 and 1%+/-1% at day 42, p< or =0.001 vs. day 0).
      Radiolabeled microsphere-derived LAD flow, normalized to left circumflex flow,
      correspondingly increased between day 0 and day 42 (0.14+/-0.02 to 0.90+/-0.07,
      p<0.02). CONCLUSIONS: Collateral development occurs relatively early and rapidly
      in this chronic canine model. Myocardial contrast echocardiography using harmonic
      imaging and intravenous injection of microbubbles can uniquely track the spatial
      and temporal course of collateral growth, and may be a powerful tool for
      noninvasively mapping the efficacy of therapeutic angiogenic strategies in vivo.

PMID- 10933380
TI  - The bubbles and the science of life.

PMID- 10933381
TI  - Effects of a nitrate-free interval on tolerance, vasoconstrictor sensitivity and
      vascular superoxide production.
AB  - OBJECTIVES: In the present study, we tested whether a nitrate-free interval is
      able to prevent increases in vascular superoxide (O2*-) and the development of
      hypersensitivity to vasoconstrictors and whether this may result in restoration
      of vascular nitroglycerin (NTG) sensitivity. BACKGROUND: Intermittent NTG-patch
      treatment (12 h patch on/patch-off) has been shown to increase ischemic periods
      in patients with stable coronary arteries, suggesting a rebound-like situation
      during the patch-off period. Recently, we demonstrated that long-term treatment
      with NTG induces tolerance, which was in part related to increases in vascular
      O2*- and increased vasoconstrictor sensitivity. METHODS: New Zealand white
      rabbits received a continuous application of NTG patches (0.4 mg/h) or an
      intermittent application of NTG patches (12 h patch on, 12 h patch off) for three
      days. Isometric tension studies were performed with aortic rings, and vascular
      O2*- was estimated using lucigenin-derived chemiluminescence (5 micromol/liter).
      Expression of the copper/zinc (Cu/Zn) superoxide dismutase (SOD) was assessed by
      Western blotting, and SOD activity was measured by autooxidation of 6
      hydroxydopamine. RESULTS: Continuous treatment with NTG caused tolerance to NTG,
      cross-tolerance to the endothelium-dependent vasodilator acetylcholine, increased
      vascular O2*-, reduced Cu/Zn SOD expression and increased sensitivity to
      vasoconstrictors such as phenylephrine, serotonin and angiotensin II. On/off
      treatment with NTG improved tolerance, corrected endothelial dysfunction and
      decreased vascular O2*-. In addition the reduction in SOD expression was less
      pronounced, whereas increases in the sensitivity to vasoconstrictors such as
      phenylephrine and serotonin remained nearly unchanged. CONCLUSIONS: Enhanced
      vasoconstrictor sensitivity may explain, at least in part, the rebound phenomena
      observed in patients during a 12-h NTG patch-off period.

PMID- 10933382
TI  - Modulation of in vivo cardiac hypertrophy with insulin-like growth factor-1 and
      angiotensin-converting enzyme inhibitor: relationship between change in myosin
      isoform and progression of left ventricular dysfunction.
AB  - OBJECTIVES: Supplemental myocardial hypertrophy induced by insulin-like growth
      factor (IGF)-1 may prevent transition from hypertrophy to heart failure under
      chronic mechanical overload. BACKGROUND: Several studies have suggested that IGF
      1 treatment may be beneficial in chronic heart failure. In addition, recent
      studies indicated that the amount of alpha-myosin heavy chain (MHC) plays a
      significant hemodynamic role in large animals including humans. METHODS: We
      treated Dahl salt-sensitive hypertensive rats on a long-term basis with IGF-1.
      The effects were compared with those produced by treatment using a sub
      antihypertensive dose of temocapril, an angiotensin-converting enzyme (ACE)
      inhibitor. At 11 weeks, when these rats displayed compensated left ventricular
      hypertrophy (LVH), they were randomized to three groups: 1) IGF group (3
      mg/kg/day); 2) temocapril group (1 mg/kg/day); and 3) vehicle (control) group.
      RESULTS: After 15 weeks, the control rats showed left ventricular (LV)
      enlargement and severe LV dysfunction and rapidly died of pulmonary congestion
      (mean survival time: 16.8+/-0.5 weeks). The survival time was significantly
      shortened (15.6+/-0.3 weeks) in the IGF-1 group but significantly prolonged
      (19.5+/-0.6 weeks) in the temocapril group. The rats in the IGF-1 group showed
      accelerated LV dilation and dysfunction. Of the several parameters investigated,
      it was found that the relative amounts of MHC isoforms differed among the three
      groups. The alpha-MHC mRNA level was decreased by 52% (p<0.01) in the IGF group,
      while it increased by 58% (p<0.01) in the temocapril group compared with the
      control group. These changes were related to the progression of LV dysfunction.
      CONCLUSIONS: Supplemental myocardial hypertrophy with long-term IGF-1 treatment
      may not be beneficial if concentric LVH already exists. Our data suggest that IGF
      1 may not protect myocardial performance when its hypertrophic effect aggravates
      the reduction of alpha-MHC. By contrast, the ACE inhibitor may improve myocardial
      function and prognosis by preventing the down-regulation of this isoform.

PMID- 10933384
TI  - Do no harm.

PMID- 10933383
TI  - Exercise training restores ischemic preconditioning in the aging heart.
AB  - OBJECTIVES: To investigate the effects of ischemic preconditioning in hearts from
      adult and both sedentary and trained senescent rats. BACKGROUND: Ischemic
      preconditioning does not prevent postischemic dysfunction in the aging heart,
      probably because of reduction of cardiac norepinephrine release. Exercise
      training can reverse the age-related decrease of norepinephrine production.
      METHODS: We investigated the effects on mechanical parameters of ischemic
      preconditioning against 20 min of global ischemia followed by 40 min of
      reperfusion in isolated perfused hearts from adult (six months) and sedentary or
      trained (six weeks of graduated swim training) senescent (24 months) rats.
      Norepinephrine release in coronary effluent was determined by high-performance
      liquid chromatography. RESULTS: Final recovery of percent-developed pressure was
      significantly improved after preconditioning in adult hearts (91.6+/-9.6%) versus
      unconditioned controls (54.2+/-5.1%, p<0.01). The effect of preconditioning on
      developed pressure recovery was absent in sedentary but present in trained
      senescent hearts (39.6+/-4.1% vs. 64.3+/-7.1%, p<0.05). Norepinephrine release
      significantly increased after preconditioning in adult and in trained but not in
      sedentary senescent hearts. The depletion of myocardial norepinephrine stores by
      reserpine abolished preconditioning effects in adult and trained senescent
      hearts. CONCLUSIONS: In adult and trained but not in sedentary senescent hearts,
      preconditioning reduces postischemic dysfunction and is associated with an
      increase in norepinephrine release. Preconditioning was blocked by reserpine in
      both adult and trained senescent hearts. Thus, exercise training may restore
      preconditioning in the senescent heart through an increase of norepinephrine
      release.

PMID- 10933385
TI  - President's page: geographic variations in delivery of cardiovascular care: an
      issue of great importance to cardiovascular specialists.

PMID- 10933386
TI  - Plasma concentrations of bacterial lipopolysaccharide: a marker of infection or
      inflammation?

PMID- 10933387
TI  - Coronary heart disease and Chlamydia pneumoniae DNA in blood mononuclear cells.

PMID- 10933388
TI  - The electric cardiographic abnormalities are not hidden!

PMID- 10933389
TI  - Xid-like phenotypes: a B cell signalosome takes shape.

PMID- 10933390
TI  - Monomeric and oligomeric complexes of the B cell antigen receptor.
AB  - The current structural model of the B cell antigen receptor (BCR) describes it as
      a symmetric protein complex in which one membrane-bound immunoglobulin molecule
      (mIg) is noncovalently bound on each side by an Ig-alpha/Ig-beta heterodimer.
      Using peptide-tagged Ig-alpha proteins, blue native polyacrylamide gel
      electrophoresis (BN-PAGE), and biosynthetical labeling of B cells, we find that
      the mIg:Ig-alpha/Ig-beta complex has a stoichiometry of 1:1 and not 1:2. An anti
      Flag stimulation of B cells coexpressing Flag-tagged and wild-type Ig-alpha
      proteins results in the phosphorylation of both Ig-alpha proteins, suggesting
      that on the surface of living B cells, several BCR monomers are in contact with
      each other. A BN-PAGE analysis after limited detergent lysis provides further
      evidence for an oligomeric BCR structure.

PMID- 10933391
TI  - Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent
      mechanism.
AB  - Lymphocyte enhancer factor-1 (LEF-1) is a member of the LEF-1/TCF family of
      transcription factors, which have been implicated in Wnt signaling and
      tumorigenesis. LEF-1 was originally identified in pre-B and T cells, but its
      function in B lymphocyte development remains unknown. Here we report that LEF-1
      deficient mice exhibit defects in pro-B cell proliferation and survival in vitro
      and in vivo. We further show that Lef1-/- pro-B cells display elevated levels of
      fas and c-myc transcription, providing a potential mechanism for their increased
      sensitivity to apoptosis. Finally, we establish a link between Wnt signaling and
      normal B cell development by demonstrating that Wnt proteins are mitogenic for
      pro-B cells and that this effect is mediated by LEF-1.

PMID- 10933393
TI  - Diversity in the CDR3 region of V(H) is sufficient for most antibody
      specificities.
AB  - All rearranging antigen receptor genes have one or two highly diverse
      complementarity determining regions (CDRs) among the six that typically form the
      ligand binding surface. We report here that, in the case of antibodies, diversity
      at one of these regions, CDR3 of the V(H) domain, is sufficient to permit
      otherwise identical IgM molecules to distinguish between a variety of hapten and
      protein antigens. Furthermore, we find that somatic mutation can allow such
      antibodies to achieve surprisingly high affinities. These results are consistent
      with a model in which the highly diverse CDR3 loops are the key determinant of
      specificity in antigen recognition in both T cell receptors (TCR) and antibodies,
      whereas the germline-encoded CDR1 and CDR2 sequences are much more cross
      reactive.

PMID- 10933392
TI  - Phospholipase Cgamma2 is essential in the functions of B cell and several Fc
      receptors.
AB  - Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of
      PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have
      decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell
      deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens
      are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent
      antibody production is absent. The similarity to Btk- or Blnk-deficient mice
      demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma
      signaling is also defective, resulting in a loss of collagen-induced platelet
      aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4
      function. The results define a signal transduction pathway broadly utilized by
      immunoglobulin superfamily receptors.

PMID- 10933394
TI  - CD19 regulates Src family protein tyrosine kinase activation in B lymphocytes
      through processive amplification.
AB  - CD19 regulates constitutive and antigen receptor-induced signaling thresholds in
      B lymphocytes through its unique cytoplasmic domain. Herein, we demonstrate a
      novel molecular mechanism where interactions between CD19 and Lyn amplify basal
      and antigen receptor-induced Src family kinase activation. Lyn expression was
      required for CD19 tyrosine phosphorylation in primary B cells. Experiments with
      purified proteins demonstrated that CD19-Y513 was Lyn's initial phosphorylation
      and binding site. This led to processive phosphorylation of CD19-Y482, which
      recruited a second Lyn molecule, allowing for transphosphorylation and
      amplification of Lyn activation. In vivo, CD19 deficiency impaired, and CD19
      overexpression enhanced, Lyn kinase activity. Thus, CD19 functions as a
      specialized adapter protein for the amplification of Src family kinases that is
      crucial for intrinsic and antigen receptor-induced signal transduction.

PMID- 10933395
TI  - Coreceptor reversal in the thymus: signaled CD4+8+ thymocytes initially terminate
      CD8 transcription even when differentiating into CD8+ T cells.
AB  - A central paradigm of T cell development is that CD4+8+ (DP) thymocytes
      differentiate into CD4+ or CD8+ T cells in response to intrathymic signals that
      extinguish transcription of the inappropriate coreceptor molecule. Contrary to
      this prevailing paradigm, we now demonstrate that signaled DP thymocytes
      initially terminate CD8 transcription even when differentiating into CD8+ T
      cells. Remarkably, thymocytes that have selectively terminated CD8 transcription
      can be signaled by IL-7 to differentiate into CD8+ T cells by silencing CD4
      transcription and reinitiating CD8 transcription, events we refer to as
      "coreceptor reversal." These observations significantly alter our understanding
      of CD8+ T cell differentiation and lead to a new perspective ("kinetic
      signaling") on CD4/CD8 lineage determination in the thymus. These observations
      also suggest a novel mechanism by which bipotential cells throughout development
      can determine their appropriate cell fate.

PMID- 10933397
TI  - Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by
      controlling association of histone deacetylases and acetylases with MEF2.
AB  - TCR signaling leading to thymocyte apoptosis is mediated through the expression
      of the Nur77 family of orphan nuclear receptors. MEF2 has been shown to be the
      major transcription factor responsible for calcium-dependent Nur77 transcription.
      Cabin1 was recently identified as a transcriptional repressor of MEF2, which can
      be released from MEF2 in a calcium-dependent fashion. The molecular basis of
      repression of MEF2 by Cabin1, however, has remained unknown. We report that
      Cabin1 represses MEF2 by two distinct mechanisms. Cabin1 recruits mSin3 and its
      associated histone deacetylases 1 and 2; Cabin1 also competes with p300 for
      binding to MEF2. Thus, activation of MEF2 and the consequent transcription of
      Nur77 are controlled by the association of MEF2 with the histone deacetylases via
      the calcium-dependent repressor Cabin1.

PMID- 10933398
TI  - The CD28-related molecule ICOS is required for effective T cell-dependent immune
      responses.
AB  - While CD28 is critical for expansion of naive T cells, recent evidence suggests
      that the activation of effector T cells is largely independent of CD28/B7. We
      suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important
      role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T
      cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS
      attenuates lung mucosal inflammation induced by Th2 but not Th1 effector
      populations. Our data indicate a critical function for the third member of the
      CD28 family in T cell-dependent immune responses.

PMID- 10933396
TI  - Notch1 signaling promotes the maturation of CD4 and CD8 SP thymocytes.
AB  - Notch proteins regulate many developmental processes. Notch1 is highly expressed
      on thymocytes, but its role in regulating their development is not known. We show
      that activation of Notch1 signaling in CD4+CD8+ double positive thymocytes
      promotes the maturation of both CD4+ and CD8+ single positive thymocytes and that
      this occurs in the absence of interactions between the T cell receptor and MHC
      molecules expressed on thymic epithelial cells. We have also identified several
      genes that are transcriptionally regulated by Notch1 in T cells and show that
      they are upregulated during maturation into both single positive lineages. These
      observations suggest that Notch1 signaling plays a role in promoting maturation
      into both the CD4 and CD8 T cell lineages.

PMID- 10933399
TI  - The NOD Idd9 genetic interval influences the pathogenicity of insulitis and
      contains molecular variants of Cd30, Tnfr2, and Cd137.
AB  - Previous analyses of NOD mice have shown that some genes control the development
      of both insulitis and diabetes, while other loci influence diabetes without
      reducing insulitis. Evidence for the existence of a gene only influencing
      diabetes, Idd9 on mouse chromosome 4, is provided here by the development of a
      novel congenic mouse strain, NOD.B10 Idd9. NOD.B10 Idd9 mice display profound
      resistance to diabetes even though nearly all develop insulitis. Subcongenic
      analysis has demonstrated that alleles of at least three B10 genes, Idd9.1,
      Idd9.2, and Idd9.3 are required to produce Idd9-mediated diabetes resistance.
      Candidate genes with amino acid differences between the NOD and B10 strains have
      been localized to the 5.6 cM Idd9.2 interval (Tnfr2, Cd30) and to the 2.0 cM
      Idd9.3 interval (Cd137).

PMID- 10933400
TI  - Export of antigenic peptides from the endoplasmic reticulum intersects with
      retrograde protein translocation through the Sec61p channel.
AB  - Antigenic peptides are translocated by the TAP peptide transporter from the
      cytosol into the endoplasmic reticulum (ER) for loading onto MHC class I
      molecules. Peptides that fail to bind need to be removed from the ER. Here we
      provide evidence that peptide export utilizes the Sec61p translocon as
      demonstrated by blocking this channel with bacterial exotoxin. Peptide export
      interferes with the retrotranslocation of beta2-microglobulin from the ER to the
      cytosol, suggesting similar pathways for the disposal of proteins and
      oligopeptides. Peptide export requires ATP supply to the ER lumen but is
      independent of ATP hydrolysis.

PMID- 10933401
TI  - Essential role for the dsRNA-dependent protein kinase PKR in innate immunity to
      viral infection.
AB  - The double-stranded (ds) RNA-dependent protein kinase PKR is considered to play
      an important role in interferon's (IFN's) response to viral infection. Here, we
      demonstrate that mice lacking PKR are predisposed to lethal intranasal infection
      by the usually innocuous vesicular stomatitis virus, and also display increased
      susceptibility to influenza virus infection. Our data indicate that in normal
      cells, PKR primarily prevents virus replication by inhibiting the translation of
      viral mRNAs through phosphorylation of eIF2alpha, while concomitantly assisting
      in the production of autocrine IFN and the establishment of an antiviral state.
      These results show that PKR is an essential component of innate immunity that
      acts early in host defense prior to the onset of IFN counteraction and the
      acquired immune response.

PMID- 10933402
TI  - Clonal acquisition of inhibitory Ly49 receptors on developing NK cells is
      successively restricted and regulated by stromal class I MHC.
AB  - We report an in vitro stroma-dependent system for the clonal growth and
      differentiation of natural killer (NK) cells from lymphoid-restricted bone marrow
      progenitors or bone marrow NK1.1+ cells. Strikingly, the potential to initiate
      expression of specific Ly49 receptors becomes increasingly restricted as NK cells
      develop. Moreover, when NK cells express a Ly49 receptor specific for stromal
      cell class I MHC, they are less likely to initiate expression of another Ly49
      receptor in the clonal culture system. The results indicate multiple roles for
      stromal cells in NK cell development, in supporting clonal growth, in initiation
      of Ly49 receptor expression, and in formation of the NK cell receptor repertoire.

PMID- 10933403
TI  - Functional foods and health claims: a public health policy perspective.
AB  - OBJECTIVE: To propose a policy framework for the regulation of functional foods
      and health claims within a public health context. DESIGN: This article reviews
      the empirical evidence and public health principles associated with functional
      foods and health claims to analyse the issues, challenge the assumptions that
      have emerged and explore options for moving forward. SETTING: Functional foods
      and health claims are among the more controversial and complex issues being
      debated by food regulators internationally. Proponents of functional foods and
      health claims state that functional foods may reduce health care expenditure and
      health claims are a legitimate nutrition education tool that will help them
      inform consumers of the health benefits of certain food products. Conversely,
      opponents of these developments respond that it is the total diet that is
      important for health, not so-called 'magic bullets'. Moreover, they argue that
      health claims will enable manufacturers to indulge in marketing hyperbole and
      essentially blur the distinction between food and drugs. This topic provides a
      valuable case study of public policy in relation to food and health. CONCLUSION:
      The need to maintain a general prohibition on health claims while accommodating
      specific exemptions supported by scientific substantiation is recommended.
      Nutrition education and monitoring and evaluation are integral to the proposed
      regulatory framework. The intention of this policy position is to encourage
      research and development of innovative food products while avoiding an
      inappropriate medicalization of the general food supply.

PMID- 10933404
TI  - Dietary pattern, nutrient intake and growth of adolescent school girls in urban
      Bangladesh.
AB  - OBJECTIVE: To investigate the dietary pattern and nutritional status of
      adolescent girls attending schools in Dhaka city and to examine the association
      with various social factors. DESIGN: Cross-sectional study. SETTING: Girls high
      schools in Dhaka city. SUBJECTS: A total of 384 girls, aged from 10 to 16 years,
      who were students of classes VI to IX of 12 girls high schools in Dhaka city were
      selected by systematic random sampling. Nutrient intake was assessed using the 24
      h recall method and the usual pattern of food intake was examined using a 7-day
      food frequency questionnaire. RESULTS: The prevalence of undernutrition among the
      participants assessed as stunting was 10% overall with younger girls being less
      stunted (2%) than older girls (16%), whereas 16% were thin with relatively more
      of the younger girls (21%) being thin than of the older girls (12%). Based on the
      usual pattern of food intake, a substantial proportion of the girls did not
      consume eggs (26%), milk (35%) or dark green leafy vegetables (20%). By
      comparison, larger proportions consumed meat (50%) and fish (65%) at least four
      times a week. For the intake of energy and protein, only 9 and 17% of the girls,
      respectively, met the recommended daily allowance (RDA). For nearly 77% of the
      girls, the intake of fat was less than the recommendation. Intakes less than the
      RDA were found for iron (77% of the girls), calcium (79%), vitamin A (62%),
      vitamin C (67%), and riboflavin (96%). Based on the food consumption data,
      cereals were the major source of energy (57%), thiamin (67%), niacin (63%) and
      iron (37%). Animal sources supplied 50% of dietary protein. Cooking fats were the
      principal source of fat (67%) in the diet. Milk was the major contributor for
      riboflavin and preformed vitamin A (retinol). Leafy vegetables and fruits were
      the main sources of provitamin A (carotenes). The girls from families with less
      educated parents were more likely to be thin and short for their age. Those girls
      from families with lower incomes and less educated parents had a dietary pattern
      which tended to be poor with regard to egg, milk, meat and fruit, with lower
      intakes of protein, fat and riboflavin. CONCLUSION: The findings indicate that
      the diets of these girls tended to be inadequate both for macronutrients and
      micronutrients, with significant health implications. There was also a
      relationship between the family income and the education of the parents with the
      nutritional status of the girls.

PMID- 10933405
TI  - A longitudinal study of iron status in children at 12, 24 and 36 months.
AB  - OBJECTIVES: To assess iron status in a sample of clinically well, Caucasian
      children and explore the complex factors which contribute to iron deficiency
      during infancy. DESIGN: Infants recruited at birth and followed longitudinally at
      1, 2, 3, 4, 5, 6, 9, 12, 24 and 36 months; feeding practices and socioeconomic
      data recorded. Iron status assessed using venous blood at 12, 24 and 36 months.
      SETTING: Baseline data recorded in the maternity unit. Follow-up visits took
      place in the infants' homes and blood sampling in a paediatric hospital.
      SUBJECTS: Subjects comprised a mixed socioeconomic group of healthy children (n =
      121). Blood samples taken from 85, 72 and 67% at 12, 24 and 36 months,
      respectively. RESULTS: Prevalence of anaemia (Hb < 110 g l(-1)) in the
      longitudinal sample (n = 76) increased from 2.6% at age 12 months to 9.2% at 24
      months, and at age 36 months (n = 70) was 8%. The most significant finding was
      that at age 12 months, cows' milk consumption was negatively associated with iron
      status. Other variables also had an influence. At both 24 and 36 months the most
      significant predictor of iron status was earlier iron status. CONCLUSIONS:
      Infants born to anaemic mothers or mothers who smoke and infants who consume
      cows' milk during infancy are at increased risk of developing anaemia. Breast
      milk is the ideal, but for the infant who is not breast fed an iron fortified
      formula should be used. Advice to mothers should focus on the importance of
      introducing nutrient dense complementary foods, such as meat, which contains
      readily absorbable iron.

PMID- 10933406
TI  - Sales data of a supermarket--a tool for monitoring nutrition interventions.
AB  - OBJECTIVE: The aim of the study was to examine the daily variations in sales data
      for individual food items in a supermarket and to assess the usefulness of the
      computerized sales data of supermarkets for reliable monitoring and evaluation of
      shopping behaviour. DESIGN: Longitudinal observational study. SETTING: The study
      was carried out in one supermarket in Mikkeli, Finland. Seventy-nine packed food
      items from food groups important for salt and fat intake were monitored. In all
      food groups both 'healthier' and 'reference' products were included for
      assessment of both direct sales and proportional sales. The sales data were
      collected daily for 2 months in May and September 1996 by reading the European
      Article Numbering (EAN) codes of the packed foods. RESULTS: The proportional
      sales turned out to be a more stable and useful measure than the direct sales
      data and the variation remained the same when the monitoring time was increased
      from 1 week to 1 month. CONCLUSION: Proportional sales data are proposed as a
      tool for measuring the effect of nutrition interventions and also as a possible
      indirect assessment for population salt and fat intake.

PMID- 10933407
TI  - Effects of reduced-fat diets with different fatty acid compositions on serum
      lipoprotein lipids and apolipoproteins.
AB  - OBJECTIVE: To compare the effects on serum lipoproteins of three isocaloric diets
      with reduced total fat and saturated fatty acid (SFA) contents but with different
      proportions of monounsaturated (MUFA) and polyunsaturated fatty acids (PUFA).
      DESIGN: A low-fat diet (LF) provided 20 en% fat, 7.9% SFA, 7.8% MUFA, 3.0% PUFA;
      a high-PUFA diet (HP) 26 en% fat, 7.5% SFA, 8.2% MUFA, 8.1% PUFA; and a high-MUFA
      diet (HM) 26 en% fat, 7.3% SFA, 14.1% MUFA, 3.2% PUFA. Diets were consumed for 8
      weeks in a parallel design, after 2 weeks on a habitual diet with 33-34 en% fat,
      13-14% SFA, 12% MUFA, 6% PUFA, and followed by an 8-week period on habitual diet.
      Compliance to diet was monitored by repeated food records and weekly visits to a
      nutritionist. SUBJECTS: 45 free-living, middle-aged couples who were randomly
      allocated into the three diet groups; 43 men and 44 women completed the study.
      RESULTS: During the diet periods, a small but significant reduction in body
      weight of 0.4-1.0 kg was observed in all groups. Similar and significant
      reductions of mean weight-adjusted serum total cholesterol (4-8%), low-density
      lipoprotein (LDL) cholesterol (7-11%), and high-density lipoprotein (HDL)
      cholesterol (8-11%) were observed during the diets. HDL2-cholesterol and
      apoprotein (apo) A-I levels were reduced whereas HDL3-cholesterol and apoA-II
      increased. ApoB was significantly decreased during the HM diet only. Serum
      triglycerides increased significantly during diets LF (25%, P < 0.01) and HP
      (19%, P < 0.05) but not during diet HM (5%, NS). CONCLUSIONS: Reduction in the
      intake of total fat and saturated fatty acids reduced serum LDL-cholesterol and
      HDL2-cholesterol concentrations irrespective of the relative proportions of MUFA
      and PUFA in the diets. The results suggest that there might be some advantage in
      increasing the proportion of MUFA in low-fat diets, since the HM diet rich in
      MUFA reduced apoB and slightly attenuated the increase in serum triglycerides
      that is commonly associated with dietary fat reduction.

PMID- 10933408
TI  - Wernicke-Korsakoff syndrome in Sydney hospitals after 6 years of thiamin
      enrichment of bread.
AB  - OBJECTIVES: To estimate the incidence of Wernicke's encephalopathy (WE) and
      Korsakoff's psychosis (KP) before and after the introduction of thiamin
      enrichment of bread in Australia. DESIGN AND SUBJECTS: Inpatient records were
      examined in 17 major public general hospitals in greater Sydney for the 4 years
      1993-96 (inclusive) with the International Classification of Diseases (ICD) 9
      diagnoses 265.1 (WE), 291.1 and 294.0 (KP). Relevant clinical data were recorded
      on a specially designed form so that cases could be classified as confirmed or
      probable WE, confirmed or probable KP, confirmed or probable Wernicke-Korsakoff
      syndrome (WE + KP) or not WE or KP. The average number of cases of WE + KP was 38
      acute (new) cases and 69 total (acute + chronic) cases per annum for all the
      hospitals combined. RESULTS: This study used the same methods as our earlier
      retrospective examination of Wernicke-Korsakoff cases in essentially the same
      hospitals for 1978-93. Records for 1993 were thus pulled twice and, while
      individual cases (using hospital index number) did not always coincide, the total
      numbers for 1993 were 69 and 70. For the 5 years after 1991 the number of acute
      cases of WE and KP in Sydney hospitals was 61% of the number for the 5 years
      before 1991 (P<0.01). There is, however, no continuing downward trend.
      CONCLUSIONS: These results are consistent with a 40% reduction of the incidence
      of acute WE and KP since bread has been enriched with thiamin. The disease
      complex has, however, not been eliminated. To achieve this, further public health
      action would be needed, such as addition of thiamin to beer.

PMID- 10933409
TI  - Development and testing of a quantitative food frequency questionnaire for use in
      Kerala, India.
AB  - OBJECTIVE: To develop and test a food frequency questionnaire (FFQ) for use in
      rural areas of Kerala, India. DESIGN: Based on food use and market surveys of the
      study area, a quantitative 81-item interviewer-administered FFQ was developed. A
      validation study was conducted consisting of 24-h diet recalls (24HR)
      administered on 8 days randomly selected over an entire year and two
      administrations of the FFQ, one at the beginning of the 1-year period and the
      other at the end. FFQ and 24HR-derived nutrient scores were compared using
      correlation and regression analyses and by examining differences in the nutrient
      scores. SETTING: Rural villages in Ernakulum district, Kerala, South India.
      SUBJECTS: In each of 30 households, the male head of household and female food
      preparer were enrolled. RESULTS: Pearson (parametric) correlation coefficients
      (r(p)) averaged about 0.50 in comparing nutrient scores derived from the 24HR
      with those from the first FFQ and about 0.55 in comparing the second FFQ. On
      average, Spearman correlation coefficients (r(s)) were slightly lower than the
      r(p) in comparing the scores derived from the first FFQ, but virtually identical
      for the second FFQ. Regression analyses indicated better agreement in the
      comparison of the 24HR-derived scores with the first FFQ than the second FFQ.
      Difference scores, however, tended to be larger in comparing the first FFQ scores
      with the 24HR. CONCLUSIONS: This FFQ produces results broadly comparable to those
      used in Europe and North America, indicating its suitability for comparing
      exposures within a study population in reference to health-related endpoints.

PMID- 10933410
TI  - Magnitude, determinants and impact of under-reporting of energy intake in a
      cohort study in Greece.
AB  - OBJECTIVES: To investigate the frequency and the determinants of under-reporting
      in a semi-quantitative food frequency questionnaire used in the Greek segment of
      the European Prospective Study on Nutrition, Cancer and Health (EPIC study).
      DESIGN: A food frequency questionnaire was completed by 9262 adult men and women.
      The questions included in this questionnaire covered the average intake of
      approximately 150 food items and beverages over 1 year. Evaluation of under
      reporting was conducted on an individual basis taking into account the expected
      daily variation of nutritional intakes during the time period of recording.
      Individuals whose energy intake was lower than 1.14*BMR (basal metabolic rate)
      were defined as under-reporters. SETTING: Urban and rural population of Greece.
      RESULTS: The data indicated underestimation of energy intake by 11.8% of
      individuals enrolled. Results from a logistic regression model indicated that
      body mass index (BMI), gender, age and educational level were significant
      predictors of under-reporting. The proportion of overweight participants (BMI
      >30) who tend to under-report energy intake was more than twice that of normal
      weight individuals. Men were significantly more prone to under-reporting compared
      to women, while low education individuals under-report more often than others.
      Exclusion of under-reporters generated, as expected, mean nutrient values that
      were significantly higher (by about 6%) than those derived from the total number
      of participants. When the nutrient values were energy-adjusted, however, or were
      expressed as percentages of energy intake for macronutrients or as nutrient
      densities for micronutrients, the emerging differences were minimal and generally
      statistically not significant. CONCLUSIONS: Under-reporting does exist and it is
      more extensive among men, those with low education levels and the overweight
      participants. Adjustment for energy intake minimizes the bias generated by under
      reporting with respect to particular nutrients and their association with various
      disease outcomes in the cohort.

PMID- 10933411
TI  - Alcohol consumption and risk of benign proliferative epithelial disorders of the
      breast: a case-cohort study.
AB  - OBJECTIVE: To study the association between alcohol consumption and risk of
      benign proliferative epithelial disorders (BPED) of the breast (conditions which
      are thought to have premalignant potential). DESIGN: Case-cohort study. SETTING:
      The study was undertaken within the 56,537 women in the Canadian National Breast
      Screening Study (NBSS) who completed self-administered dietary questionnaires.
      (The NBSS is a randomized controlled trial of screening for breast cancer in
      women aged 40-59 years at recruitment.) SUBJECTS: The study subjects were the 657
      women in the dietary cohort who were diagnosed with biopsy-confirmed incident
      BPED. For comparative purposes, a subcohort consisting of a random sample of 5681
      women was selected from the full dietary cohort. After exclusions for various
      reasons, the analyses were based on 557 cases and 5028 non-cases. RESULTS: When
      compared to non-drinkers, rate ratios (95% CI) for those consuming > 0 and < or
      =10 g of ethanol day(-1), >10 and < or =20 g day(-1), >20 and < or =30 g day(-1)
      and >30 g day(-1) were 0.35 (0.27-0.45), 0.26 (0.18-0.39), 0.29 (0.18-0.48), and
      0.23 (0.13-0.40), respectively (the associated P value for the trend was 0.089).
      Similar findings were obtained from analyses conducted separately in the screened
      and control arms of the NBSS, in premenopausal and postmenopausal women, and for
      non-atypical and atypical forms of BPED, and there was little difference between
      the results for screen-detected and interval-detected BPED. CONCLUSIONS: Alcohol
      consumption was associated with a non-dose-dependent reduction in risk of BPED.

PMID- 10933412
TI  - Intake of fruits, vegetables, folic acid and related nutrients and risk of breast
      cancer in postmenopausal women.
AB  - OBJECTIVE: To determine the role of fruit and vegetable consumption and dietary
      intake of folic acid and related nutrients such as methionine, cysteine and
      alcohol in the aetiology of breast cancer. DESIGN: Population based case-control
      study. SETTING: Part of the European Community Multicentre Study on Antioxidants,
      Myocardial Infarction, and Cancer of the Breast (EURAMIC) in Berlin, Germany.
      SUBJECTS: As part of the EURAMIC study, dietary intake data were collected in 43
      postmenopausal women diagnosed with breast cancer between 1991 and 1992 in
      Berlin, Germany, and compared to 106 population-based controls. RESULTS: Odds
      ratios (ORs) adjusted for major risk factors of breast cancer but not for total
      energy intake showed a non-significant inverse association between a high intake
      of vegetables (OR=0.76, 95% CI=0.48-1.20) and fruits (OR=0.74, 95% CI=0.48-1.15)
      and breast cancer. Once results were adjusted for total energy intake the
      associations became much weaker (vegetables: R=0.86, 95% CI=0.51-1.46; fruits:
      OR=0.82, 95% CI=0.51-1.32). For all nutrients, the effect of energy adjustment
      was more profound and the inverse associations disappeared when results were
      adjusted for energy intake (total folate-not energy adjusted: OR = 0.79, 95%
      CI=0.51-1.21; energy adjusted: OR=1.14, 95% CI=0.73-1.79; folate equivalents-not
      energy adjusted: OR=0.81, 95% CI=0.53-1.23; energy adjusted: OR=1.16, 95% CI=0.78
      1.74; methionine-not energy adjusted: OR=0.60, 95% CI=0.35-1.03; energy adjusted:
      OR=1.29, 95% CI=0.76-2.19; cysteine-not energy adjusted: OR=0.52, 95% CI=0.29
      0.94; energy adjusted: OR=1.22, 95% CI=0.75-1.97). Alcohol intake was inversely
      associated with breast cancer in a non-significant way, possibly due to the
      relatively low alcohol intake of the study population. CONCLUSIONS: The results
      of this study do not provide firm evidence that a high intake of fruits and
      vegetables, folic acid, methionine or cysteine reduces the risk of getting breast
      cancer.

PMID- 10933413
TI  - Relationship between alcohol and nutrient intakes and blood status indices of
      older people living in the UK: further analysis of data from the National Diet
      and Nutrition Survey of people aged 65 years and over, 1994/5.
AB  - OBJECTIVE: To examine the relationships between alcohol consumption and a range
      of nutrient intakes and blood status indices in older people. DESIGN: National
      Diet and Nutrition Survey: cross-sectional survey of nationally representative
      sample of people aged 65 years or over. SETTING: Mainland Britain during 1994/5.
      SUBJECTS: 1198 people (623 males, 575 females) aged 65 years or over, of whom 925
      were living in private households and 273 were living in institutions. RESULTS:
      Intermediate alcohol consumption (particularly 0.1-14 units week(-1); 1 unit = 8
      g) derived from a 4-day diet diary or a 12-month recall questionnaire, was
      associated with higher intakes of vitamins C, E, B1, iron, calcium, energy from
      food, carbohydrate and non-starch polysaccharides than heavy alcohol consumption
      (28 + units week(-1)) or abstinence, after adjustment for a number of factors
      (age, sex, domicile, social class, cigarette smoking, self-reported health, grip
      strength and total energy intake). Intermediate alcohol consumption was also
      associated with higher blood concentrations (independent of intake) of vitamin C,
      beta-cryptoxanthin, lutein and calcium, with the lowest concentrations being
      found in heavy alcohol users. The lowest concentrations of serum ferritin were
      found in light drinkers and the highest levels in heavier alcohol drinkers.
      Alcohol consumption ranging from 0.1 to >28 units week(-1) was directly
      correlated with intakes of B vitamins, total energy and fat, with blood
      concentrations (independent of intake) of lycopene, high density lipoprotein
      (HDL)-cholesterol, plasma pyridoxal phosphate and retinol, and with blood
      pressure and grip strength. CONCLUSIONS: Compared with abstinence and heavy
      drinking, light to moderate alcohol consumption in older people is associated
      with higher intakes of certain nutrients, and higher blood concentrations
      (independent of intake) of some micronutrient status indices, including
      antioxidants. The explanation for the latter associations remains unclear and
      further investigation is recommended. Heavier alcohol consumption is associated
      with both beneficial and adverse effects with respect to nutrient intakes and
      health status.

PMID- 10933414
TI  - Plasma fibrinogen of black South Africans: the BRISK study.
AB  - OBJECTIVE: To describe the distribution of plasma fibrinogen and relationships
      with other risk factors for coronary heart disease (CHD) and stroke in the black
      population of the Cape Peninsula. DESIGN: A cross-sectional survey of a
      stratified proportional sample of randomly selected black men and women. SETTING:
      Households in Gugulethu, Langa, Nyanga, New Crossroads, KTC, Old Crossroads and
      Khayelitsha in the Cape Peninsula, South Africa. SUBJECTS: One subject per
      household (352 men and 447 women), aged 15-64 years, voluntarily participated.
      Visitors, pregnant, lactating, ill, mentally retarded and intoxicated subjects
      were excluded. RESULTS: Mean fibrinogen (thrombin time coagulation method) of men
      and women were higher than published data for Europeans but slightly lower than
      values of black Americans. Women aged 45-54 years had the highest level (3.13+/
      0.89 g l(-1)) and men aged 15-24 years had the lowest (2.13+/-0.88 g l(-1)).
      Fifteen per cent of the men and 12% of the women had a level greater than 1
      standard deviation of the mean for their age group. Univariate and multivariate
      analyses revealed significant (P<0.05) positive correlations of fibrinogen with
      smoking habit, age, body mass index (BMI), total and low-density lipoprotein
      (LDL) cholesterol, triglycerides, blood pressure and white blood cell count, and
      significant negative correlations with high-density lipoprotein (HDL)
      cholesterol, gamma glutamyl transferase (GGT), serum iron and ferritin. The
      correlations with BMI, serum lipoproteins, iron, ferritin, and GGT suggest that
      nutritional status and therefore diet influences plasma fibrinogen. CONCLUSION:
      Relatively high fibrinogen levels, tending to cluster with other, including diet
      related, risk factors for CHD and stroke, were observed in black South Africans.
      It is suggested that fibrinogen may contribute to the high stroke incidence of
      this population group.

PMID- 10933415
TI  - Undernutrition and elevated blood lead levels: effects on psychomotor development
      among Jamaican children.
AB  - OBJECTIVE: We examined whether or not the effect of elevated blood lead levels on
      children's psychomotor development was modified by their nutritional status.
      DESIGN: Anthropometry, developmental quotients (DQs), blood lead levels and
      haemoglobin were measured in lead exposed and unexposed children with different
      levels of nutritional status. Social background and maternal height and verbal
      intelligence were also measured. Testers, anthropometrists and interviewers
      established reliabilities with a trainer before the study began. SETTING:
      Children were from two suburban areas in Kingston, Jamaica. All measurements on
      the children were carried out at a research unit. Social background and maternal
      measurements were carried out at the children's homes. SUBJECTS: The exposed
      group comprised 58 children (3-6 years) attending the same preschool which was
      situated in a lead contaminated environment. The unexposed group comprised 53
      children attending a nearby preschool without lead contamination. RESULTS: The
      exposed children had significantly higher blood lead levels and lower DQs, and
      their homes had poorer facilities than the unexposed children. The deficit in DQ
      was greater (10.6 points) among children with weight for height less than -1 SD
      (National Center for Health Statistics references) than among better nourished
      children (2 points). CONCLUSIONS: Undernourished children exposed to lead may
      have more serious developmental deficits than better nourished children.

PMID- 10933416
TI  - The relationship between spermine content of human milk during the first
      postnatal month and allergy in children.
AB  - DESIGN: Qualitative case study and mathematical model. SETTING: Belgium.
      OBJECTIVES: To evaluate the correlation between the polyamine mean concentration
      of the milk drunk during the first postnatal month and the appearance of allergy
      in children who drank this milk. RESULTS: A model that describes the dependence
      of the allergy appearance with the spermine mean concentration of milk drunk
      during the first postnatal month was established. CONCLUSIONS: This model shows
      that 5.02 nmol ml(-1) of spermine is a critical value to prevent the appearance
      of allergy.

PMID- 10933417
TI  - Food consumption patterns in the adult population of the Basque Country (EINUT
      I).
AB  - OBJECTIVE: Dietary surveys are a valuable tool in nutrition surveillance
      programmes to monitor the nutritional status of a group or population of a
      country. The objective of this study was to assess the food consumption pattern
      in the adult population of the Basque Country (Spain). DESIGN: A cross-sectional
      nutritional survey was carried out in 1990. Dietary habits were assessed by means
      of '24-h recall' during 3 non-consecutive days and a food frequency
      questionnaire. SETTING: Population survey in the Basque Country (Spain).
      SUBJECTS: Random sample of the adult population (25-60 years) in the Basque
      Country (n = 2348). RESULTS: Results draw a food pattern characterized by a high
      consumption of meat, 163+/-3.04 g day(-1) (mean +/- SEM), supplied mainly by
      poultry, butchery products, veal and fish (88+/-2.68 g day(-1)). The average
      consumption of milk and dairy products was 359+/-5.19 g day(-1), although 39% of
      the sample did consume less than 2 portions from this group of foods daily. Olive
      oil was the most widely used fat for cooking (45%), followed by sunflower seed
      oil (30%). Cereals supplied 21.5% of the average energy intake and the
      consumption of vegetables and garden products was 159+/-3.13 g day(-1). Only 29%
      of the group usually had 2 or more portions of vegetables per day. Women consumed
      higher amounts of chocolate, cookies, sweets and coffee (P < 0.01) than men.
      Younger adults consumed more meat (P < 0.01), while the older community consumed
      more fish, vegetables and fruit (P < 0.01). More highly educated people consumed
      more dairy products, vegetables and butter (P < 0.01). Conversely, less educated
      people consumed higher amounts of olive oil, pulses and bread (P < 0.01).
      CONCLUSIONS: The dietary pattern observed in the Basque Country, although in
      keeping with its traditions, is in harmony with the actual dietary trends in
      Mediterranean countries. In order to satisfy the dietary guidelines suggested by
      the Spanish Society of Community Nutrition, it would be desirable to gradually
      increase the consumption of vegetables, fresh garden produce, fruit and cereals.
      At the same time, it would be advisable to decrease the consumption of animal
      products (whole fat dairy products, meat, added fats) so the proportion of energy
      intake from fat can be reduced by 5% (3% from saturated fatty acids).

PMID- 10933418
TI  - Factors which influence 'healthy' eating patterns: results from the 1993 Health
      Education Authority health and lifestyle survey in England.
AB  - OBJECTIVES: This study explores the factors that influence eating patterns in a
      nationally representative sample of the English population. DESIGN: Subjects were
      interviewed in 1993; questions covered basic demographic details, attitudes about
      nutrition, and they completed a short food frequency questionnaire that had
      previously been validated. Cluster analysis was used to summarize dietary intake
      into more or less healthy clusters. SETTING: A random sample of the English
      population. SUBJECTS: A cross-sectional survey of 5553 men and women (response
      rate 70%) aged between 16 and 74 years. RESULTS: As defined from the cluster
      analysis about half the sample were currently reporting a more healthy diet;
      respondents in the better educated middle-aged demographic cluster were more
      likely to report eating a more healthy diet than respondents in the younger lower
      income family cluster. About three-quarters of all respondents believed that they
      either already ate a healthy diet or had changed to a healthy diet in the last 3
      years. For those respondents who said they were eating a healthy diet about half
      of them were eating a more healthy diet. Respondents who had not changed their
      diet were more likely than those who had to believe that healthy foods were just
      another fashion (men 34% v. 13%; women 30% v. 12%), or expensive (men 50% v. 35%;
      women 53% v. 40%); they were less likely to care about what they ate (men 45% v.
      13%; women 27% v. 7%). Nearly three-quarters of all respondents agreed that
      experts never agree about what foods are good for you. Younger, low-income
      families, and those who smoked, were the group least likely to be eating a more
      healthy diet. CONCLUSIONS: The results of this study suggest that about half of
      the population has reported a change to a healthier diet over the last 3 years
      and that overall about half of the population report eating a healthy diet. Those
      who had not made any change and were currently reporting a less healthy diet were
      more likely to smoke and come from the 'worse off group in the survey; they were
      also more likely to hold negative attitudes about healthy eating. A more focused
      and integrated approach to promoting healthy lifestyle in general is required,
      while at the same time ensuring that there is continued support for the majority
      of the population who have made healthy dietary changes.

PMID- 10933419
TI  - Validation with biological markers for food intake of a dietary assessment method
      used by Swedish women with three different dietary preferences.
AB  - OBJECTIVES: To validate a dietary assessment method, a 4-day food record together
      with a duplicate portion technique, with biological markers for food intake.
      DESIGN: Four days of duplicate portions were collected in parallel with food
      recording. A 24-h urine sample and the faeces corresponding to the food intake
      (using a coloured marker) were collected. Completeness of urine and faeces
      collections was assessed using para-aminobenzoic acid (PABA) in urine and cadmium
      in faeces, respectively. Biomarkers of food intake (energy, protein, fibre,
      sodium, potassium, calcium) were measured in urine and faeces. SETTING: Swedish
      west coast. SUBJECTS: Non-smoking Swedish women, 20-50 years of age, consuming a
      mixed diet (n = 34), a mixed diet rich in shellfish (n = 17) or a vegetarian/high
      fibre diet (n = 23). RESULTS: The average ratio (food intake according to the
      dietary assessment methods/ biological marker) for protein, sodium, potassium and
      calcium was 0.86. This indicates an underestimation of the food intake by
      approximately 15%. The ratio of stated fibre intake to biological marker was 1.20
      for the mixed diet and the vegetarian diet group, indicating an overestimation by
      approximately 20%. CONCLUSIONS: The underestimation of the intake of protein,
      sodium, potassium and calcium by all three groups and the overestimation of the
      fibre intake by two groups indicate that underreporting is selective to certain
      nutrients and foods and to various groups of people. The two dependent dietary
      assessment methods were equally good in measuring protein intake, which indicates
      that the women recorded what they actually duplicated.

PMID- 10933420
TI  - A comparison of selected nutrient intakes derived from three diet assessment
      methods used in a low-fat maintenance trial.
AB  - OBJECTIVE: In the vast majority of surveys and research in humans, dietary data
      are obtained from self-reports: recalls; records; or historical methods, usually
      food frequency questionnaires (FFQ). This study provides a rare opportunity to
      compare data derived from all three methods. DESIGN: A crossover study of dietary
      fat in which data were collected using an average of 11.4 food records and 11.7
      24-h diet recalls. Using simple subtraction and correlation, energy and nutrient
      intakes derived from the three methods were compared to each other and with those
      derived from a single FFQ. Analysis of variance was used to evaluate sources of
      variability in nutrient intakes estimated from the individual days of records and
      recalls. SETTING: An independent, free-standing medical research institute.
      SUBJECTS: 13 men who were compliant with study procedures. RESULTS: FFQ-derived
      estimates of energy and nutrient intake were highest (e.g. 1967 kcal versus 1858
      kcal and 1936 kcal for the records and recalls, respectively). Mean differences
      in energy and nutrient intakes and their variances were lowest and correlation
      coefficients highest in comparing the records and recalls (e.g. for fat the mean
      difference was 5.0 g, and r = 0.85). Analysis of variance of individual days of
      record- and recall-derived data (n = 300) revealed that there was no effect due
      to either method (record or recall) or the sequence of administration.
      CONCLUSIONS: Results of this study indicate that the FFQ overestimated dietary
      intake. Energy and nutrient results obtained from the records and recalls were
      interchangeable. However, based on smaller SDs around the means, it appears that
      the recalls may perform slightly better in estimating dietary intake in groups
      such as these well-educated, highly compliant men.

PMID- 10933421
TI  - Curriculum design for professional development in public health nutrition in
      Britain.

PMID- 10933422
TI  - Food photographs: practical guidelines I. Design and analysis of studies to
      validate portion size estimates.

PMID- 10933423
TI  - Food photographs: practical guidelines II. Development and use of photographic
      atlases for assessing food portion size.

PMID- 10933424
TI  - Predicting percentage of individuals consuming foods from percentage of
      households purchasing foods to improve the use of household budget surveys in
      estimating food chemical intakes.
AB  - OBJECTIVE: To examine the hypothesis that there is sufficient agreement between
      percentage of households purchasing selected foods using household budget surveys
      and percentage of individuals consuming these foods as determined in individual
      based surveys to allow the former to act as a surrogate for the latter when
      estimating food chemical intakes using household budget data. DESIGN: Database
      study. SETTING: Databases from Sweden, The Netherlands. Ireland and the UK.
      SUBJECTS: 319 foods (Sweden n = 60, The Netherlands n = 80, Ireland n = 90, UK n
      = 89). RESULTS: Pearson correlations demonstrated a high degree of linear
      association between % households purchasing and % consumers (r = 0.86).
      Regression analysis defined a close positive relationship between the two
      datasets (slope 0.95, intercept +2.74). Across countries, using the regression
      equation, the % households predicted % consumers to within 5% of the true value
      for between 33 and 48% of foods and to within 10% for between 53 and 78% of
      foods. CONCLUSIONS: Values for % households can be used as a crude surrogate for
      % consumers and can thus play a role in improving estimates of food additive
      intake.

PMID- 10933425
TI  - Reducing iron deficiency anaemia due to heavy menstrual blood loss in Nigerian
      rural adolescents.
AB  - OBJECTIVE: Menstrual disorders are common in young women, and heavy menstrual
      blood losses (MBL) are an important cause of anaemia. Menstrual morbidity
      normally goes untreated in developing countries where cultural barriers also
      serve to mask the problems. We investigated the prevalence of menstrual
      morbidity, and measured MBL and its relationship to iron deficiency in a rural
      adolescent population. The rationale was to assess whether or not reducing heavy
      MBL could be part of a strategy to reduce iron deficiency anaemia. SETTING: Rural
      village in south-east Nigeria. DESIGN: Cross-sectional survey. SUBJECTS: The
      study included all non-pregnant, unmarried nulliparous girls (< 20 years) who had
      menstruated, and who lived in K'Dere village. METHODS: A field worker allocated
      to each girl completed a questionnaire, and supervised recovery and collection of
      soiled pads and ensured blood sampling. MBL was measured using the standard
      alkaline haematin method. Haemoglobin (Hb), serum iron, transferrin saturation
      and protoporphyrin levels (ZPP) were also measured. RESULTS: 307 girls completed
      MBL measurements; 11.9% refused to participate. 12.1% had menorrhagia (> 80 ml);
      median MBL was 33.1 ml. Menorrhagia was more frequent in girls who had
      menstruated for > 2 years (P = 0.048), and had longer duration of menses (P <
      0.001). Iron status as measured by haematocrit, serum iron, transferrin
      saturation and ZPP values was inversely related to MBL. Neither height nor body
      mass index for age was associated with current iron status. CONCLUSIONS: The
      level of menorrhagia detected (12%) may be an 'expected' level for a condition
      which often has no underlying pathology. Heavy MBL is one of the most important
      factors contributing to iron deficiency anaemia. Measures are needed to alleviate
      menstrual disorders, and improve iron status. Oral contraceptives can be part of
      a strategy to reduce anaemia, particularly for adolescents at high risk of
      unwanted pregnancies.

PMID- 10933426
TI  - The nutritional status of older Rwandan refugees.
AB  - OBJECTIVE: To assess the nutritional status of older people in an unstable
      situation. DESIGN: Anthropometric and socioeconomic data were collected cross
      sectionally. Body mass index (BMI), arm muscle area (AMA) and arm fat area (AFA)
      were calculated to evaluate nutritional status. For 41 subjects with kyphosis,
      height was estimated from arm span using sex-specific regression equations from
      the non-kyphotic group. SETTING: The study was carried out in the post-emergency
      phase in a Rwandan refugee camp in Karagwe district, north-west Tanzania.
      SUBJECTS: Measurements were obtained from 413 men and 415 women aged 50-92 years.
      RESULTS: The prevalence of undernutrition (BMI < 18. 5) was 19.5% in men and
      13.1% in women and was higher above age 60 years in both sexes: in men the
      prevalences were 23.2% and 15.0% (P < 0.05) and in women 15.1% and 10.9% for the
      older and younger age groups respectively. AMA, which is important in relation to
      the ability to remain active and independent, was also significantly lower in
      older age groups. No difference was found in AFA. The proportion with low BMI was
      much higher in the group with kyphosis. CONCLUSIONS: Even in this population of
      older Rwandans who managed to reach the camp and survive in exile for more than a
      year, undernutrition does occur and is more prevalent at an advanced age. The
      higher prevalence of undernutrition in kyphotic people illustrates the importance
      of including this group in nutritional status assessments.

PMID- 10933427
TI  - The validation of physical activity instruments for measuring energy expenditure:
      problems and pitfalls.
AB  - OBJECTIVE: To review and categorize the problems associated with undertaking
      physical activity validation studies and to construct a checklist against which
      any study could be compared. RESULTS: The studies reviewed demonstrated problems
      in defining the dimension of physical activity that is of interest and in the
      selection of an appropriate comparison technique. Ideally this should be closely
      related to the true exposure of interest and assess that exposure objectively and
      without correlated error from the study instrument in question. In many studies
      inappropriate comparison methods have been chosen which do not measure the true
      underlying exposure and which are likely to have correlated error. The choice of
      study populations, the frame of reference of the exposure measurement and the use
      of appropriate statistical methods are also problematic areas. CONCLUSIONS: There
      is no ideal measurement instrument or validation study design that is suitable
      for all situations. However, the checklist in this paper provides a means whereby
      the appropriateness of studies already undertaken or at the planning stage can be
      assessed.

PMID- 10933428
TI  - Effectiveness of a dietary intervention strategy in general practice: effects on
      blood lipids, health and well-being.
AB  - OBJECTIVES: To evaluate the effect of a dietary treatment programme on blood
      cholesterol concentration in hypercholesterolaemic patients in general practice
      and to analyse subjectively experienced side-effects. DESIGN: A 1-year parallel
      trial comparing a new treatment programme with conventional treatment. SETTING:
      General practitioners in Roskilde county, Denmark. SUBJECTS: 355 men and women,
      aged 20-60 years, with a persistent blood cholesterol concentration above age-
      and gender-specific cut-off points (265 in an intervention group and 90 in a
      control group). INTERVENTION: A treatment strategy based on collaboration between
      doctor and dietitian using individual dietary advice and feedback from measured
      biological parameters. MAIN OUTCOME MEASURES: Serum lipids, body weight, blood
      pressure, dietary behaviour, health parameters, quality of life parameters and
      acceptance by patients and general practitioners. RESULTS: Total blood
      cholesterol concentration decreased by 14% (1.07 mmol l(-1), P < 0.0001) in 159
      patients in the intervention group, not having any lipid altering drug during
      treatment, in addition to 3% from screening to start of treatment. In 65 patients
      in the control group, without any lipid altering drug, the reduction of
      cholesterol concentration was 4% (0.27 mmol l(-1), P < 0.01; intervention vs.
      control P < 0.001). In the intervention group overweight subjects (body mass
      index > 30) reduced body weight by 6% (P < 0.0001). Systolic blood pressure was
      reduced by 11% (P < 0.0001) and diastolic blood pressure by 10% (P < 0.0001) and
      19% (P < 0.003) for intervals 90-110 mmHg and > 110 mmHg, respectively. Risk
      score decreased and self-assessed health, physical and psychological well-being
      improved. CONCLUSIONS: The treatment strategy tested proved to be efficient,
      without side-effects and well accepted by patients and general practitioners. The
      results strongly suggest that hypercholesterolaemia can efficiently be treated
      non-pharmacologically in general practice.

PMID- 10933429
TI  - Outcome research.

PMID- 10933430
TI  - The neurofibromatoses. An overview.
AB  - The last two decades have seen clinical and molecular delineation of the
      different forms of neurofibromatosis. Differentiation of these forms is not just
      an academic exercise: their natural history, management and genetic counselling
      are quite different. Of the numerical classifications of neurofibromatosis
      proposed in the past, only neurofibromatosis type 1 (Nf1) and neurofibromatosis
      type 2 (Nf2) are now well delineated clinically and have been shown to be
      distinct at the molecular level. For both forms of neurofibromatosis, patients
      with clinical generalised disease have been demonstrated to be mosaic at the
      molecular level, and features of segmental or mosaic Nf1 and Nf2 have been
      delineated. Other reported forms of neurofibromatosis are rarer; they include
      Watson syndrome, hereditary spinal neurofibromatosis, familial intestinal
      neurofibromatosis, autosomal dominant cafe-au-lait spots alone, autosomal
      dominant neurofibromas alone, and schwannomatosis, the latter believed to be a
      variant of Nf2. Further delineation is needed for individuals having overlapping
      features of Noonan's syndrome and neurofibromatosis (the so-called
      Noonan/neurofibromatosis syndrome) and the syndrome of "multiple naevi, multiple
      schwannomas and multiple vaginal leiomyomas". In this article we review the forms
      of neurofibromatosis which we believe are true clinical entities. Particular
      attention is given to the neurological manifestations of neurofibromatosis.

PMID- 10933431
TI  - Presenile primary cognitive decline or Alzheimer's dementia: 7-year clinical and
      neuropsychological follow-up.
AB  - Early diagnosis of presenile Alzheimer's disease (AD), which would serve for
      prognosis and for guiding choices of treatment, is still an important, difficult
      task for the clinical neurologist. We studied 24 patients, 12 of whom had minor
      cognitive impairment or questionable dementia (PICD) and 12 who met NINCDS-ADRDA
      criteria for presenile AD (PAD). Using clinical, neuropsychological,
      neurophysiological and neuroradiological methods, we followed the patients up to
      two disease end-points: death or untestable condition. This paper concentrates on
      the main clinical and neuropsychological findings relative to these two end
      points. All PAD patients evolved into clinically evident Alzheimer-type dementia,
      became untestable within 60 months and died within 72 months. Only 3 of the PICD
      patients became demented; 2 of them died during the follow-up and 1 died eight
      months later. The other 9 PICD patients showed only moderate cognitive decline,
      compatible with normal aging processes. Neurophysiological and neuroradiological
      findings might be an important tool for arriving at a correct early diagnosis,
      when they are assessed with clinical neuropsychological data.

PMID- 10933432
TI  - Word-list learning in normally developing children: effects of semantic
      organization and retention interval.
AB  - Immediate and 15-min delayed recall of semantically related or unrelated word
      lists was investigated in 144 normally developing children ranging from 5 to 10
      years of age. Immediate recall for the related and unrelated lists increased in a
      parallel fashion as a function of age. The ability to cluster semantically
      related items during immediate recall also improved with age. However, in no age
      class recall scores and clustering indexes were significantly associated.
      Forgetting rate passing from the last immediate to the delayed recall trial
      increased for the unrelated list but decreased for the related list of words as a
      function of age. Results of regression analyses revealed that a developmental
      increase in forgetting on the unrelated list was actually due to the higher
      number of words recalled in the last immediate trial by older children. As for
      the related list, instead, the larger reliance on the clustering strategy of
      recall by older children was responsible for the progressive reduction of
      forgetting.

PMID- 10933433
TI  - Systemic lupus erythematosus and myoclonic epileptic manifestations.
AB  - Systemic lupus erythematosus (SLE) frequently involves the central nervous system
      (CNS) and, in fact, epileptic manifestations may be one of the earliest symptoms
      of SLE. These early occurrences of epilepsy, however, can easily be misdiagnosed
      as indication of pure epileptic syndrome when the SLE diagnosis is still largely
      incomplete. We present a young girl who developed myoclonic photosensitive
      seizures at the onset of the illness, erroneously diagnosed as manifestation of a
      "pure" epileptic syndrome. Shortly after the onset of an anticonvulsant therapy
      (lamotrigine), there was a remarkable impairment of the general clinical
      condition: at that time a diagnosis of SLE was made and a specific treatment
      began. However, the seizures persisted and evolved toward status epilepticus
      which needed pentobarbitone therapy in an intensive care unit (ICU). After
      recovery, the girl gradually got better and during the 23 months of follow-up she
      received only corticosteroid therapy and did not experience seizures nor SLE
      relapses.

PMID- 10933434
TI  - Motor evoked potentials in a case of stiff-man syndrome: a longitudinal study.
AB  - The clinical and neurophysiological findings in a patient with a typical stiff
      man syndrome and their three-year evolution are described. The patient had high
      titers of anti-glutamic acid decarboxylase antibodies in both serum and
      cerebrospinal fluid. Magnetic resonance imaging (MRI) of brain and spinal cord
      was normal. Transcranial magnetic stimulation (TMS) revealed a distinctive motor
      evoked potential (MEP) pattern in proximal lower limb muscles consisting of
      markedly increased MEP amplitudes and MEP/M ratios, reduced excitability
      thresholds, and absent silent period. However, MEP latencies, central and
      peripheral conduction times and amplitudes obtained by magnetic spinal root
      stimulation were normal. Treatment with benzodiazepine and baclofen normalized
      both the clinical picture and the MEP values. TMS may be useful both as a
      diagnostic tool and to monitor the response to drug treatment.

PMID- 10933435
TI  - Outcome research and patient-oriented measures in the multiperspective assessment
      of neurological and musculoskeletal disorders. Consensus Conference: Third Roman
      Neurophysiology Day, Outcome Research in Neurology and in Musculoskeletal
      Disorders--24 October 1998.

PMID- 10933436
TI  - Requests for electromyography from general practitioners and specialists:
      critical evaluation.

PMID- 10933437
TI  - Assessing olfaction in the Italian population: methodology and clinical
      application.
AB  - Disorders of the sense of smell are receiving growing clinical as well as
      experimental attention. Indeed, several neurological conditions have been
      associated with peripheral or central deficits of the olfactory system. In recent
      years, particular emphasis has been attributed to the early and severe olfactory
      impairment in neurodegenerative diseases, such as Alzheimer's dementia and
      Parkinson's disease. Olfactory assessment has also been included in comprehensive
      pre- and post-surgical evaluations of temporal lobe epilepsy. Moreover, the
      request for standardized methods of olfactory evaluation by forensic and
      occupational medicine is greatly increasing. Despite this requirement, there is
      no agreement in the Italian neurological community on olfactory assessment. This
      lack prompted us to generate a battery of standardized tests capable of bypassing
      cross-cultural differences in olfactory assessment and to be potentially useful
      in the clinical as well as experimental settings. Procedures of assessment of
      olfactory acuity (detection threshold), identification (multiple choice odor
      naming), discrimination (differentiation between similar/dissimilar odorants) and
      memory (recognition of a substance previously smelled) are fully described. In
      order to control bias factors depending upon the nature of the investigated
      disorder and the applied olfactory tasks, a minimal complementary
      neuropsychological assessment is recommended.

PMID- 10933438
TI  - Interferon beta treatment in relapsing-remitting multiple sclerosis: a post
      marketing study in Lombardia, Italy. Multiple Sclerosis Centers of Lombardia,
      Italy.
AB  - The aim of the study was to evaluate the efficacy of interferon beta-1a (IFN-beta
      1a) and beta-1b (IFN-beta-1b) in clinical practice for the treatment of relapsing
      remitting multiple sclerosis (RR MS). Patients were selected and prospectively
      monitored according to a predefined protocol. An appropriate form was prepared to
      collect clinical data of multiple sclerosis patients attending the MS Centers of
      Lombardia, Italy. On 30 June 1998, 317 patients were treated with IFN-beta-1b and
      156 with IFN-beta-1a. Basal expanded disability status scale (EDSS) and relapse
      frequency were similar in both groups of patients. The annual relapse rate
      consistently decreased from 1.76 to 0.63 at 1 year and to 0.51 at 2 years for the
      IFN-beta-1b group and from 1.6 to 1.0 at 1 year for the IFN-beta-1a group.
      Disability remained stable in most patients. Dropouts (20.5%) were affected by
      more active disease compared to patients who continued to be treated. This study
      confirms the efficacy of both treatments, showing a more marked effect than
      expected from the clinical trials' results, probably due to differences in
      selection criteria and exclusion of dropouts.

PMID- 10933439
TI  - Chronic neuroborreliosis in infancy.
AB  - Lyme disease is a polymorphic and multisystemic disease caused by Borrelia
      burgdorferi. Neurological manifestations are found in 10%-50% of cases. We
      present 2 cases followed for 5 and 6 years of chronic relapsing-remitting
      neuroborreliosis. Diagnosis of neuroborreliosis in these cases was based on serum
      and cerebrospinal fluid findings. We discuss clinical, neurophysiological,
      laboratory and instrumental aspects regarding the difficulties of reaching a
      correct diagnosis. Further studies, especially in the field of immunology, should
      help identify the mechanisms responsible for the disease becoming chronic. With
      this knowledge, it may be possible to design immunological therapies for
      relapses, and to prevent the evolution of the disease.

PMID- 10933440
TI  - Italian multicentre study of carpal tunnel syndrome: clinical-neurophysiological
      picture and diagnostic pathway in 461 patients and differences between the
      populations enrolled in the northern, central and southern centres. Italian CTS
      Study Group.
AB  - The economic trend in our country, as in other countries, now requires us to pay
      more attention to the social and economic aspects of health. Therefore, it is
      important to evaluate the diagnostic pathway and the socioeconomic aspects of
      pathologies. The Italian CTS Study Group performed a wide multicentre and
      multidimensional study (through a patient-, physician- and neurophysiologically
      oriented evaluation) on 461 idiopathic CTS patients to evaluate the clinical
      neurophysiological picture and the diagnostic pathway. The whole population and
      the differences between the populations enrolled in the neurophysiological
      centres of the northern, central and southern parts of Italy were analysed. This
      study provided new and interesting information. As concerns the whole population,
      we observed different diagnostic pathways in relation to the level of schooling.
      As concerns the comparison of the populations, the southern centres have a
      population of CTS patients with higher frequency of hand stress and more severe
      nerve impairment.

PMID- 10933441
TI  - Usefulness of segmental and comparative tests in the electrodiagnosis of carpal
      tunnel syndrome: the Italian multicenter study. Italian CTS Study Group.
AB  - The Italian CTS Study Group performed a wide multicentric and multiparametric
      study to quantify the increase of electrodiagnostic sensitivity using an extended
      neurophysiological protocol and particularly segmental and comparative tests. The
      study also evaluated the clinical features of carpal tunnel syndrome (CTS)
      diagnosed by these tests, using validated physician- and patient-oriented
      measurements. The study group was composed of 740 patients for a total of 1123
      idiopathic CTS hands. Overall, the sensitivity of standard tests (median digit
      wrist sensory conduction velocity and wrist-thenar distal motor latency) was
      83.5%. Comparative/segmental tests disclosed abnormal findings in a further 11.4%
      of cases, providing CTS electrodiagnosis in about 7 of 10 "standard negative"
      cases. The overall sensitivity of the electrodiagnostic protocol was 94.9%. The
      CTS population diagnosed by segmental/comparative tests had a clinical picture
      characterized by a high percentage of pain, and severe discomfort but no
      limitation in functional daily activity. Our data confirm the usefulness of a
      complete neurophysiological assessment by using segmental/comparative tests when
      standard tests yield normal results.

PMID- 10933442
TI  - Transitory and permanent visual field defects induced by occipital lobe seizures.
AB  - Visual field defects are rarely associated with epilepsy. We report two patients
      with a long history of cryptogenetic occipital epilepsy. Both patients suffer
      complex partial crises accompanied by concentric reduction of the visual field
      followed, in the first one, by a prolonged left homonymous hemianopsia, and in
      the second one, by a permanent right inferior quadrantopsia. Occipital and
      occipito-temporal epileptic activity has been registered between seizures in both
      patients, and in one patient also during the seizure itself. Differential
      diagnosis has been considered, especially with migraine.

PMID- 10933443
TI  - A case of segmental myoclonus in amputation stump: evidence for spinal generator
      and physiopathogenetic hypothesis.
AB  - We describe a 68-year-old woman who experienced pain and phantom limb sensation
      following an above-the-knee amputation of the right leg. A month later, the
      patient had myoclonic jerks of the stump. Polymyo-graphic recordings showed
      synchronous jerks in the vastus medialis and adductors of the thigh on the right
      side. The patient responded to clonazepam. We conclude that the myoclonic jerks
      were of spinal cord origin.

PMID- 10933444
TI  - Familiar protein C deficiency and cerebral vein thrombosis in a young adult
      patient.

PMID- 10933445
TI  - Treatment of chronic inflammatory demyelinating polyneuropathy.
AB  - The management of chronic inflammatory demyelinating polyradiculoneuropathy
      (CIDP) is the main topic of this review. A few comments will also be made about
      treatment of the demyelinating form of paraproteinaemic demyelinating
      polyneuropathy (PDN) and of multifocal motor neuropathy (MMN). The review briefly
      describes the main characteristics of these neuropathies, and examines case
      series and trials which evaluated the principal therapeutic strategies for CIDP,
      PDN and MMN, such as intravenous immunoglobulin (IVIg) therapy, steroid
      treatment, plasma exchange and immunosuppressor administration. Controlled trials
      demonstrated that IVIg, steroid treatment and plasma exchange are effective in
      CIDP. For PDN the therapeutic strategies are the same as for idiopathic CIDP, but
      usually the clinical response is poorer. For MMN, IVIg therapy is definitely the
      first choice treatment.

PMID- 10933446
TI  - Neuronal ceroid lipofuscinoses: a review.
AB  - Neuronal ceroid lipofuscinoses (NCLs) are among the most common neurodegenerative
      diseases in childhood but rarely present in adulthood. The main symptoms are
      psychomotor deterioration, visual failure, epilepsy and motor disturbances. The
      NCLs are morphologically characterized by the accumulation of lipopigments within
      numerous cell types and loss of neurons. Pathogenesis is unknown. The current
      clinical classification recognizes six classic types of NCL and several atypical
      forms. Electrophysiological and neuroradiological findings may be of diagnostic
      significance, but disease recognition rests on the demonstration of a typical
      ultrastructural pattern. Genetic studies have demonstrated that several different
      genetic loci are involved in the pathogenesis of NCL, but the molecular
      mechanisms underlying neuronal death and lipopigment accumulation are not
      understood.

PMID- 10933447
TI  - Motor representation of the hand in the human cortex: an f-MRI study with a
      conventional 1.5 T clinical unit.
AB  - The purpose of this study was to show a gradient of possible bilateral activation
      for movements of the non-dominant vs. dominant hand, as well as for areas
      involved in complex vs. simple hand movements. A standard 1.5 T magnetic
      resonance imaging (MRI) system has been utilized to localize the cortical motor
      hand areas, using the blood oxygen level dependent contrast (BOLDc) technique and
      single-section fast low-angle shot (FLASH) imaging. Ten normal right-handed
      subjects volunteered for the study. The motor tasks consisted of simple (flexion
      extension) finger movements of either hand, and complex movements (finger-to
      thumb opposition in a repeating, pre-planned sequence) of the non-dominant hand.
      Simple movements caused contralateral activation of the primary motor area (MA);
      ipsilateral activation was observed for the non-dominant hand only. Supplementary
      motor area (SMA) was also activated, with a clear contralateral prevalence. The
      ratio of bilateral activation of MA did not change with complex movements of the
      non-dominant hand, while SMA as well as lateral premotor area were largely
      bilaterally activated in this task. In conclusion, the ipsilateral MA is
      activated for movements--even simple--performed with the non-dominant hand. There
      is widespread functional activity, involving both contralateral and ipsilateral
      SMA, for complex movements.

PMID- 10933448
TI  - Italian multicentre study of carpal tunnel syndrome: study design. Italian CTS
      Study Group.
AB  - In September 1996, during a carpal tunnel syndrome (CTS) symposium, the Italian
      CTS Study Group was funded. The group designed a strict clinical and
      neurophysiological protocol for performing a wide multicentre study on idiopathic
      CTS in hands. In addition to the traditional evaluations, the group also adopted
      a validated patient-oriented measurement in order to obtain comprehensive and
      reliable data for the clinical picture. The study was designed to: (1) better
      assess the clinical picture of the CTS population, especially using new
      measurement tools (patient-oriented); (2) evaluate the sensitivity of an
      electrodiagnostic protocol; (3) re-evaluate the validity of a neurophysiological
      classification; and (4) evaluate the influence of social status and quantify some
      of the aspects regarding economic and social costs. The study design is
      described.

PMID- 10933449
TI  - Utility of multimodal evoked potential study and electroencephalography in
      mitochondrial encephalomyopathy.
AB  - We performed electroencephalography (EEG) and multimodal evoked potential (EP)
      studies in 16 patients with various forms of mitochondrial encephalomyopathy
      (ME). The electrophysiological investigations revealed signs of involvement of
      the peripheral and central nervous system (CNS) in 14 patients, with a high
      incidence of visual-EP (VEP) alterations, indicative of visual pathway
      vulnerability in mitochondrial diseases. No specific pattern of abnormalities
      emerged and, in particular, clinical and laboratory findings did not correlate
      with each other. EP (particularly VEP and electroretinogram) investigations
      should be part of the diagnostic work-up of patients with mitochondrial disorders
      in order to better characterize the clinical picture, disclose involvement of
      specific sensory systems of the CNS, and assess patients with atypical clinical
      presentations.

PMID- 10933450
TI  - Population-based case-control study of essential tremor.
AB  - Current epidemiologic data on the association between environmental factors and
      essential tremor (ET) are scanty. In a population-based case-control study we
      investigated the relationship between some putative risk factors and ET. In the
      present study, we included all subjects identified during a door-to-door
      prevalence survey in a Sicilian community, affected by ET, and alive on 1
      November 1987 (n=31). Of the 31 prevalent cases of ET, we were able to contact 28
      subjects. Twenty-eight controls were randomly selected from the general
      population and matched to each case for age and sex. Exposure variables were
      investigated by interviewing the patients and their controls or close relatives,
      using a structured questionnaire. The odds for habitual alcohol consumption were
      0.3, indicating a protective effect. The odds for exposure to agricultural
      chemicals and domestic animals were 2.5 and 2.7, respectively, suggesting a role
      as potential risk factors. However, the associations found by us were not
      statistically significant.

PMID- 10933451
TI  - Hypokalemic thyrotoxic paralysis: a rare cause of tetraparesis with acute onset
      in Europeans.
AB  - We describe a 21-year-old Italian male affected by hypokalemic tetraparesis with
      acute onset. In the emergency ward, the patient was agitated, with tachycardia
      (140/min) and systolic hypertension (180/70 mm Hg). He was not able to flex the
      lower extremities against a light resistance and furthermore, he was hypotonic
      and without tendon reflexes. One hour later he developed strength deficit of the
      upper extremities as well. Biochemical analyses revealed severe hypopotassemia
      (2.1 meg/l). After administration of 140 meq potassium phosphate, the patient
      began to improve, and 12 h after the onset he was able to walk normally.
      Successive investigations documented an undiagnosed case of Graves' disease.
      Thyrotoxic hypokalemic paralysis has been observed almost only in Asians,
      however, with this case and others reported, we believe that it should be
      considered as a cause of muscular paralysis also in Caucasians.

PMID- 10933452
TI  - Prevalence of microembolic signals in patients with different types of mono
      leaflet and bi-leaflet prosthetic heart valves.
AB  - Microembolic signals (MES) have been described in patients with different types
      of prosthetic valves. The aim of our study was to compare prevalence of MES in
      patients with mono-leaflet and bi-leaflet valves, and to correlate them with
      different clinical and echocardiographic parameters. We evaluated 42 patients, 15
      with mono-leaflet and 27 with bi-leaflet valves, with 30-minute bilateral
      simultaneous transcranial Doppler monitoring for the identification of MES. All
      patients performed blood testing for international normalized ratio (INR), color
      coded duplex of supra-aortic vessels, and echocardiography. Eighteen patients
      (43%) showed MES; 61% of MES were detected bilaterally, 17% only on the left and
      22% only on the right middle cerebral artery (MCA), with no interhemispheric
      difference. MES did not correlate with patient's age, echocardiographic
      parameters, INR, presence of atrial fibrillation, or site of valve replacement.
      One (7%) of the 15 patients with mono-leaflet valves had MES, as opposed to 17
      (63%) of the 27 with bileaflet valves (p=0.0003). Patients with bileaflet valves
      and MES had valves of older implantation and, only for aortic valves, larger
      valve size.

PMID- 10933453
TI  - X-linked adrenoleukodystrophy: first report of the Italian Study Group.
AB  - In this paper we report Italian data on X-linked adrenoleukodystrophy (ALD)
      collected from 1985 to 1997. This disease appears to be the most common of the
      peroxisomal disorders and is associated with a functional defect of the
      peroxisomal very long chain fatty acid (VLCFA) oxidation. In Italy 117 cases have
      been recognized, but many cases may be unrecognized due to the heterogeneous
      clinical manifestations that vary from mild to very severe forms. To control the
      devastating course of this disease two therapeutic approaches are under
      evaluation: bone marrow transplantation (BMT) and dietary treatment based on a
      mixture of glyceroyl trioleate (GTO) and glyceroyl trierucate (GTE). Our
      experience of 68 subjects submitted to dietary treatment shows that almost all
      patients with signs of cerebral involvement at the beginning of treatment
      worsened or died, patients with the milder form, adrenomyeloneuropathy (AMN),
      remained stable, while 4 of the 15 presymptomatic subjects developed neurological
      signs of the disease. In recent years a more accurate selection of patients and
      donors for BMT has given favourable results, but some strict criteria should be
      respected.

PMID- 10933455
TI  - The Italian Journal of Neurological Sciences included in the Cochrane Master
      List.

PMID- 10933454
TI  - Neuropsychological and neuroimaging correlates in corticobasal degeneration.
AB  - The aim of this study was to correlate neuropsychological and neuroimaging
      findings in corticobasal degeneration (CBD). Three patients with clinical
      criteria for CBD were examined by means of neuropsychological tests, brain
      magnetic resonance imaging (MRI), and flow and metabolism neuroimaging
      techniques. Neuropsychological assessment revealed impairment in executive
      functions, manual dexterity and motor programming with significant asymmetry
      between upper limbs. Ideomotor and oral apraxia were also detected, and memory
      deficits were observed in one patient. MRI revealed cortical dilation of the
      frontal and peri-rolandic regions, symmetrical in one case and asymmetrical in
      the other two cases. An increased T2 signal intensity in the posterolateral
      putamen and substantia nigra ipsilateral to the cortical atrophy was observed in
      one patient. Asymmetries of both frontal and parietal cortices and basal ganglia
      were detected in all three patients by 18-fluorodeoxyglucose positron emission
      tomography; temporal region hypometabolism was associated in one patient. These
      cortical and subcortical asymmetries were observed in two patients by single
      photon emission tomography with the tracer technetium Tc 99m hexamethyl
      propylenamine oxime; cortical asymmetry was observed in only one patient. The
      results showed that functional neuroimaging findings correlated well with
      neuropsychological aspects in CBD. Neuroimaging and neuropsychological
      correlations may contribute toward understanding anatomical and functional
      abnormalities associated with this neurodegenerative disorder.

PMID- 10933456
TI  - Intravenous gammaglobulin treatment in chronic progressive multiple sclerosis.

PMID- 10933457
TI  - Requests for electromyography from general practitioners and specialists:
      critical evaluation.
AB  - In order to improve the quality of service and limit costs of a local
      electromyographic service, the requests for electromyographic (EMG) examination
      issued by general practitioners and specialists were critically evaluated. The
      diagnoses suspected by referring doctors were compared with medical history and
      clinical data to analyze (1) the utility of EMG for the final diagnosis and (2)
      the concordance with that of the neurophysiologist and with the EMG results. In
      1994 and 1995, there were 3482 patients referred to the EMG service. Only
      patients undergoing EMG for the first time (2706 subjects) were considered. In
      76.6% of cases, the referring doctor had indicated the suspected diagnosis in the
      request. This diagnosis was compatible with medical history, symptoms and the
      results of neurological examination in 57.6% of cases. In 77.2%, the
      neurophysiologist considered the EMG useful in confirming the clinical diagnosis.
      The suspected diagnosis was confirmed by the clinical diagnosis of the
      neurophysiologist and by the EMG results in 54.2% and 45.4% of cases,
      respectively. When the request was issued by neurosurgeons, neurologists,
      orthopedists, rheumatologists and physiatrists, the suspected diagnosis was more
      accurate; as a consequence the EMG was more correctly oriented than when the
      request was issued by other specialists or by general practitioners. It is
      recommended that neurological examination be a prerequisite for EMG requests
      issued by general practitioners.

PMID- 10933458
TI  - The expression of GABA(A) receptor subunits in the substantia nigra is
      developmentally regulated and region-specific.
AB  - The substantia nigra pars reticulata (SNR) controls the spread of seizures.
      GABA(A)ergic drug (agonist or antagonist) infusions into the SNR have age
      specific and site-specific effects on flurothyl-induced seizures. Developmental
      and cell-specific regulation of GABA(A) receptor subunit expression may be
      responsible for these specific effects. To test this hypothesis, in situ
      hybridization was used to examine regional expression of alpha1 and gamma2L
      GABA(A) receptor subunit mRNAs in the SNR during development. Distinct temporal
      and spatial patterns of expression were observed. In rats at postnatal days (PN)
      21-60, fewer neurons were labeled with probes directed to alpha1 and gamma2L
      subunits in SNRanterior compared with SNRposterior. In addition, neurons in
      SNRanterior contained higher amounts of hybridization grains than in
      SNRposterior. In PN 15 rats, the labeling of neurons was relatively diffuse
      throughout the anterior and posterior SNR regions with moderate amounts of
      hybridization grains for both subunits. The finding of age-related differential
      distribution of alpha1 and gamma2L subunit mRNAs in the SNR suggests that GABA(A)
      receptor heterogeneity may play a role in the age-specific and site-specific
      effects of GABA(A)ergic agents on seizures in the SNR.

PMID- 10933459
TI  - FFT approximation in Alzheimer's disease.
AB  - The electroencephalographic modifications that occur during the course of
      Alzheimer's disease are characterised by an increase in the potential of low
      frequency bands, a diminution in the potential of alpha activity, and a change in
      the topographical distribution of the potential of all band frequencies. In this
      study, the fast Fourier transform (FFT) approximation was used to characterise
      modifications in the electroencephalogram location or orientation of the source
      of the dipole equivalent of the delta, theta, alpha1, alpha2, beta1 and beta2
      frequencies in 20 with patients with Alzheimer's disease and in a control group
      of 20 age-matched subjects. A statistical (t-test) comparison of the two groups
      revealed a significant change in the location of the dipolar source along the
      vertical axis in 18 (90%) of the patients; this change involved all the frequency
      bands. There was also a significant movement of the dipolar source of the alpha1
      band towards the anterior regions. In addition, the control group showed that
      there was a significant correlation between age and a more surface expression of
      the source of the delta, theta, alpha1 and beta1 bands.

PMID- 10933460
TI  - Utility of Tc 99m HMPAO SPECT in the early diagnosis of Rasmussen's syndrome.
AB  - Neuroradiological examinations are important in the diagnosis of Rasmussen's
      syndrome (RS), but they frequently result normal in the early phase of the
      disease. We performed Tc 99m HMPAO SPECT (single photon emission computed
      tomography) on an 11-year, 5-month-old, right-handed girl, two months since the
      first seizure. SPECT showed a reduced uptake of HMPAO in the left temporal region
      despite normal results with magnetic resonance imaging (MRI). After six months,
      she developed epilepsia partialis continua, neurological signs appeared, and MRI
      showed cortical atrophy on the left side. SPECT seems to be a useful, inexpensive
      and diffuse technology able to give information in the early phases of RS useful
      in the prevention of serious consequences of the disease within a medical
      therapeutic program (ganciclovir or intravenous immunoglobulins).

PMID- 10933461
TI  - Long-term survival in a patient with supratentorial glioblastoma: clinical
      considerations.
AB  - Glioblastoma, a malignant tumor of neuroepithelial origin, is relatively uncommon
      in childhood, during which it accounts for 7%-9% of brain tumors. A few patients
      (about 3%) live more than 5 years. We report a 13-year-old girl who was admitted
      because one month earlier she had begun to present headache and diplopia. Brain
      computed tomography (CT) showed a right frontal tumor. At operation, complete
      excision of the visible tumor was performed. Histologic examination showed that
      the tumor was a glioblastoma multiforme. The patient underwent 52 Gy of external
      beam radiotherapy to the enhancing tumor mass plus 3-cm border, and chemotherapy
      with nitrosourea (BCNU). Fourteen years, 9 months later, the patient presents
      neither neurological deficits nor radiological relapse. We confirm that younger
      age, the one immutable prognostic factor, supports a particularly aggressive
      approach to the treatment of glioblastomas.

PMID- 10933462
TI  - Encephalopathy, hearing loss and retinal occlusions (Susac's syndrome): a new
      case.
AB  - We describe a young woman with retinal arteriolar occlusions, encephalopathy, and
      hearing loss. At present this disorder is known as Susac's syndrome, a
      microangiopathy of the brain and retina whose pathogenesis is, however, unknown.
      The article reviews the clinical features of this rare, but not unusual, syndrome
      that can easily be misdiagnosed as multiple sclerosis.

PMID- 10933463
TI  - Light chain deposition disease neuropathy resembling amyloid neuropathy in a
      multiple myeloma patient.
AB  - A 65-year-old man with IgG lambda multiple myeloma developed severe
      polyneuropathy with prominent thermal-pain sensory impairment and autonomic
      failure. Although the clinical presentation suggested amyloid neuropathy, nerve
      biopsy showed the immunohistochemical and ultrastructural features typical of
      light chain deposition disease (LCDD). A precise morphologic and clinical
      description of LCDD neuropathy is given for the first time in the present report.

PMID- 10933464
TI  - Chorea as a symptom of neuroborreliosis: a case study.
AB  - Borrelia burgdorferi (Bb) can cause a large number of neurological symptoms.
      Although extrapyramidal disturbances are rare (representing less than 2% of all
      neurological complications), diffuse choreic dyskinesias have been described
      during the course of mild encephalitis. The data published in the literature
      suggest that there are clinical and neurological analogies between
      neuroborreliosis and multiple sclerosis (MS). The presence of specific anti-Bb
      antibodies in cerebrospinal fluid is a discriminating factor that allows a
      diagnosis of neuroborreliosis to be made. We describe the case of a patient with
      Lyme disease, characterised by widespread chorea and behavioural disturbances.
      Emphasis is placed on the atypical onset and evolution, the difficulties
      encountered in formulating a diagnosis, and the uncertainties concerning the
      pathophysiology and clinical/neuroradiological correlations of the disease.

PMID- 10933465
TI  - One hundred years of the Golgi apparatus: history of a disputed cell organelle.
AB  - In April 1898 at the Medico-Surgical Society of Pavia, Camillo Golgi communicated
      his finding of a novel intracellular structure, which he had detected in nerve
      cells by means of a variant of the "black reaction" he had developed earlier for
      the staining of the nervous tissue. On the basis of the "netlike" appearance and
      intracellular location of this structure, Golgi defined it as "internal reticular
      apparatus". The reality of the organelle was debated for fifty years, since some
      investigators believed that the structure, which was soon designated as Golgi
      apparatus, represented an artifact of metallic impregnation. The controversy was
      finally solved in the mid-1950s by studies based on electron microscopy. Linked
      to the cell organelle he had discovered, Golgi's contributions to cytology had a
      great impact on biomedical sciences of the twentieth century.

PMID- 10933467
TI  - Ethics and neurology in the Islamic world. Continuity and change.
AB  - The continuous developments in medicine and, consequently, in medical ethics,
      create new questions for Muslim physicians, medical jurists and religious
      authorities. This paper focuses on some aspects of Islamic medical ethics, with
      particular references to neuroethics, in the light of past and present Muslim
      literature.

PMID- 10933466
TI  - One hundred years of Golgi's "perineuronal net": history of a denied structure.
AB  - Perineuronal nets are reticular structures enwrapping cell bodies and the largest
      dendrites of several neuronal populations. Discovered by Camillo Golgi, who
      described them in detail in 1898, they were intensely studied by the most famous
      contemporary neurohistologists for about twenty years. The opinion of Ramon y
      Cajal that perineuronal nets were a fixation artifact ended the first period of
      studies. Only a few researchers, among whom the Italian neurologists Besta and
      Belloni, went on with their studies up to the 1930s documenting the morphology of
      perineuronal nets of different mammals and of man both in normal and in
      pathological conditions. Only after about fifty years, the advances in the field
      of cytochemistry allowed the elucidation of not only the actual existence of
      perineuronal nets, but also their chemical nature, showing conclusively that they
      are complex organisations of extracellular matrix molecules, namely glycoproteins
      and proteoglycans. The research on perineuronal nets today involves several
      groups engaged to elucidate their biological properties and functional role.

PMID- 10933468
TI  - Stressful life events and multiple sclerosis: a retrospective study.

PMID- 10933469
TI  - Meningeal metastases: clinical aspects and diagnosis.
AB  - The authors review the clinical and diagnostic aspects involved in leptomeningeal
      disease due to solid tumours, leukaemias and lymphomas. The importance of the
      combination of clinical findings with cerebral spinal fluid (CSF) examination and
      imaging studies in making an early diagnosis is underlined. The raising
      prevalence of this complication of systemic cancer deserves specific attention on
      the part of neurologists involved in consultation liason with general medicine
      and oncology.

PMID- 10933470
TI  - Paroxysmal positional vertigo.
AB  - Paroxysmal positional vertigo (PPV) is the peripheral vertiginous syndrome that
      is most frequently encountered in clinical practice. It is characterised by
      paroxysmal vertiginous attacks that are triggered by head movements and last no
      more than a few seconds, and is often accompanied by nausea and vomiting. The aim
      of this review is to provide a complete and updated description of the two
      principal manifestations of the syndrome: posterior semicircular canal (PSC-PPV)
      and horizontal semicircular canal PPV (HSC-PPV).

PMID- 10933471
TI  - A normative study on visual reaction times and two Stroop colour-word tests.
AB  - Two-hundred and nine normal subjects underwent a study aimed at providing norms
      for some attention tests currently used in neuropsychological examination. Norms
      were calculated taking into account the demographic variables. Our battery
      included single visuo-manual and go/no-go reaction times, and two versions of the
      Stroop Colour-Word Test. For the latter test, we employed a traditional version
      based on card presentation and a new version based on computer-assisted
      presentation. We evaluated the intercorrelation of the different tests, and
      studied the statistical regression models in order to adjust the original scores
      according to age, education and gender. Normative values were calculated
      following the Equivalent Scores method. The pattern of intercorrelation of our
      battery and the regression models of the scores are discussed with reference to
      the literature. The newly developed computer-assisted presentation of the Stroop
      test offers some advantages over the traditional version, especially with
      patients affected by spatial disorders.

PMID- 10933472
TI  - Affective disorders and multiple sclerosis: a controlled study on 65 Italian
      patients.
AB  - A high prevalence of major mood disorders in multiple sclerosis (MS) patients has
      been reported. In this study, we investigated the frequency of previous or
      present major mood disorders in 65 patients with clinically definite multiple
      sclerosis (Poser criteria) and in 31 polyneuropathy (PNP) patients. All patients
      underwent a questionnaire designed after DSM-IV definitions for major mood
      disorders. A higher lifetime risk for development of a major mood disorder was
      evident in MS patients (log rank test, p<0.001). Of all MS patients with a major
      mood disorder, at least 34% had one first-degree relative affected by a mood
      disorder, while the corresponding figure was 14% among PNP cases. Our data
      confirm the high lifetime risk for depression in MS patients and suggest that, at
      least in a subset of MS patients with depression, the genetic basis for
      depression operates with similar mechanisms as those at work in families with
      primary depression. However, this is not necessarily true for other subsets of
      depressed MS patients' families.

PMID- 10933473
TI  - Total removal of an intramedullary cavernous angioma by transthoracic approach.
AB  - Intramedullary cavernous angiomas are rare vascular malformations; all published
      cases have been surgically approached posteriorly by standard laminectomy. We
      describe the case of a 63-year-old man with an intramedullary cavernous angioma,
      anteriorly located in the thoracic spinal cord. The angioma was operated on by
      transthoracic approach and totally removed.

PMID- 10933474
TI  - Bilateral periventricular nodular heterotopia associated with coeliac disease and
      palatoschisis.
AB  - Periventricular nodular heterotopia (PNH) is considered a distinct entity in
      relation to the other forms of neuronal migration disorders (NMD), because PNH
      patients usually have normal neurological and mental examination results. We
      report the case of a 48-year-old woman with bilateral periventricular nodular
      heterotopia associated with epilepsy, coeliac disease, palatoschisis and other
      dysmorphic features. Her intelligence quotient (I.Q.) and the results of a
      neurological examination were normal, but she suffered from a drug-resistant
      epileptic syndrome characterised by predominantly generalised and sporadic
      partial seizures. It has recently been suggested that an X-linked dominant
      inheritance may play a role in bilateral periventricular nodular heterotopia, and
      it is thought that a genetic defect is probably responsible for coeliac disease.
      In our patient, a genetic disorder may have produced both diseases and the
      dysmorphic syndrome, although the coexistence of PNH, epileptic seizures, coeliac
      disease and palatoschisis could be coincidental. Further observations are needed
      to ascertain whether the simultaneous presence of these disorders is simply an
      unusual association of unrelated pathologies or a new and distinct pathological
      entity.

PMID- 10933475
TI  - Hereditary motor and sensory neuropathy type II (HMSN-II) and neurogenic muscle
      hypertrophy: a case report and literature review.
AB  - We present two siblings affected by hereditary motor and sensory type II
      neuropathy (HMSN-II) with neuromyotonia, and associated with muscle hypertrophy
      of the thighs and calves in one. We review the literature about the association
      between HMSN-II, neuromyotonia and muscle hypertrophy. Muscle enlargement in HMSN
      II is rare and may be sporadic or under genetic control. In our patient, muscle
      hypertrophy was sporadic and probably due to neuromyotonia. The relationship
      between muscle hypertrophy and neuromyotonia can be deduced by the fact that both
      conditions were reduced after diphenylhydantoin treatment (200 mg/day).

PMID- 10933476
TI  - Guidelines for the therapeutic use of botulinum toxin in movement disorders.

PMID- 10933477
TI  - Thromboembolic neurologic events in patients with antiphospholipid-antibody
      syndrome.

PMID- 10933478
TI  - The concept of consciousness: a challenge for the neuroscientist.

PMID- 10933480
TI  - Multivariate analysis of primitive reflexes in patients with human
      immunodeficiency virus type-1 infection and neurocognitive dysfunction.
AB  - To prove that primitive reflexes are independent markers of symptomatic human
      immunodeficiency virus type-1 (HIV-1) infection, a case-control study was carried
      out in a tertiary care, university teaching hospital. Thirty HIV-1-positive
      symptomatic cases, 30 seropositive asymptomatic controls and 30 HIV-1
      seronegative controls consented to participate and were selected consecutively. A
      single examiner blinded to serostatus administered the Mini-Mental State Exam and
      a structured neurological exam to each participant. Up to 45% of cases had
      cognitive impairment. The occurrence of neurologic signs between seropositive
      cases and seropositive controls was similar, but the number of primitive reflexes
      was significantly higher in cases (P < 0.001). By multivariate discriminant
      analysis, all primitive reflexes but two correctly classified 83.3% of all
      participants (P = 0.0013). The model had a positive predictive value of 97% when
      motor, mood, and cognitive symptoms were added (P = 0.0001). Primitive reflexes
      were independent predictors of HIV-1 serostatus, especially for those with
      cognitive dysfunction. Primitive reflexes should be included in future case
      definitions of HIV-1-related neurocognitive disorders.

PMID- 10933481
TI  - Photic driving response in primary headache: diagnostic value tested by
      discriminant analysis and artificial neural network classifiers.
AB  - The aim of this study was to discriminate migraine patients (MWoA) from tension
      type headache (TTH) patients and normals in order to confirm that the photic
      driving response in the medium frequency range is a marker of migraine and to
      test the hypothesis that MWoA and TTH are separate disorders based on
      electrophysiological pattern. We recruited 120 MWoA patients, 64 TTH patients,
      and 51 healthy controls without any history of headache or of migraine
      inheritance, according to International Headache Society (IHS) criteria. The
      classification method was discriminant analysis using both linear discriminant
      analysis with a stepwise selection of predictors and an artificial neural network
      classifier (NNs). The mean amplitude of the first harmonic elicited by flash
      stimulation in the 15-27 Hz range was significantly increased over Fp1, C3, C4,
      P4, O2, and O1 electrodes in MWoA and TTH patients in comparison with normal
      subjects. Using both classification methods, only the control subjects were
      correctly distinguished. When only the patient groups were matched, no
      significant difference was detectable. The increased brain response to visual
      stimulation detected in both migraine and TTH suggests a common neuronal
      dysfunction in the two headache subtypes.

PMID- 10933479
TI  - A concept of consciousness.
AB  - The term "consciousness", so widely used in clinical settings, is considered
      extremely complex and practically undefinable. Historically, consciousness was
      ignored by the great classical philosophers, and was regarded as a basic
      condition of "being". This changed with Descartes and during the ensuing
      centuries. A simplified, reductionistic and easily definable concept of
      consciousness is proposed; consciousness is proposed to consist of three main
      components: vigilance, mental contents, and selective attention. These three
      components can be investigated with modern neuroscientific methods--vigilance
      being the most readily explorable function. The striking differences between
      sleep and coma are pointed out (along with some observations on sleep
      initiation). Special attention is paid to epileptic impairment of consciousness
      and, in particular, to the spike-wave absence which is thought to be due to a
      temporary suspension of the "working memory circuits" within the frontal lobe.

PMID- 10933482
TI  - Simulating prosopagnosia through a lesion of lateral connections in a feed
      forward neural network.
AB  - We show that particular features of prosopagnosic impairment can be simulated by
      a connectionist model trained with an unsupervised learning procedure. In
      particular we describe a Kohonen's neural network which is able to correctly
      recognize and categorize a series of digitized pictures of faces when learning is
      characterized by certain parameter values, but which shows a prosopagnosic
      behavior when lateral connections are lesioned. We discuss the relationship
      between this result and some neurophysiological hypotheses about prosopagnosia.

PMID- 10933483
TI  - Motor imagery in a locked-in patient: evidence from transcranial magnetic
      stimulation.
AB  - Motor evoked potentials (MEPs) to transcranial magnetic stimulation were
      evaluated in a case of locked-in syndrome due to a large pontine infarction. In
      this patient, magnetic resonance imaging (MRI) and somatosensory evoked
      potentials demonstrated a tegmental involvement. One month after the attack, no
      MEP could be recorded from the right abductor digiti minimi (ADM) or either
      tibialis anterior muscle. On the contrary, MEPs were obtained from the left ADM,
      although with a prolonged latency and a reduced amplitude. When the patient was
      requested to think about the abduction of her paralyzed left little finger, the
      latency and the elicitability of these responses improved as compared with the
      relaxed condition. These severe MEP alterations correctly predicted a poor
      recovery of motor function in the chronic stage. However, although the tegmental
      involvement raises the question of an insufficient cortical motor arousal,
      preserved motor imagery suggested a normal cortical motor area activation.

PMID- 10933484
TI  - Locally delivered chemotherapy and repeated surgery can improve survival in
      glioblastoma patients.
AB  - We treated 54 patients, newly diagnosed for glioblastoma, with systemic
      chemotherapy (carmustine (BCNU) 100 mg/m2 and cisplatin 90 mg/m2 every 6 weeks)
      and radiotherapy soon after surgery. In 10 cases the treatment was combined with
      locoregional chemotherapy (1 mg bleomycin on days 1-2, and 3 mg mitoxantrone on
      day 3, repeated every 20 days) administered from an Ommaya reservoir. At tumor
      recurrence, all patients were treated with procarbazine, lomustine and
      vincristine (PCV); 15 of 54 were reoperated and treated with locoregional
      chemotherapy. The median time to disease progression (TTP) and overall survival
      time (ST) for the whole group were 10.8 and 23.1 months, respectively. The ST of
      the 15 reoperated patients who also received locoregional treatment at disease
      recurrence was 27.6 months; this was significantly longer than that of patients
      not reoperated and not treated locally (log-rank p=0.04). The results in our
      reoperated subgroup support the opinion that a second operation could be suitable
      if it is part of the whole program of treatment.

PMID- 10933485
TI  - Psychiatric symptoms as late onset of Wilson's disease: neuroradiological
      findings, clinical features and treatment.
AB  - We describe a case of Wilson's disease with late psychiatric onset. Major
      depressive disorder was the first clinical manifestation at the age of 38 years.
      After pharmacotherapy with antidepressive agents, a manic episode was observed.
      Extrapyramidal hand tremor and micrography were the first neurological signs.
      Emotional lability occurred during worsening of extrapyramidal signs. Diagnosis
      was based on urinary and serum copper levels, ceruloplasmin serum level, Kayser
      Fleischer ring, and liver biopsy that detected cirrhosis. Magnetic resonance
      imaging revealed basal ganglia hyperintensity on T1-weighted images, and
      hypodensity in the central part and hyperintensity in the peripheral part of the
      lentiform nucleus on T2-weighted images. Hyperintensity on T2-weighted images was
      also observed in the dorsal part of the midbrain. 123I-iodobenzamide single
      photon emission computed tomography (IBZM-SPECT) detected a normal distribution
      of the drug in the brain, with better signal in the right side and deficit of D2
      dopaminergic receptors in the basal ganglia. Abnormal manganese erythrocyte level
      was observed. Treatment was based on penicillamine, zinc salts, low-copper diet,
      antidepressant agents, interpersonal psychotherapy and neurorehabilitation.

PMID- 10933486
TI  - Radiation-induced rhombencephalopathy.
AB  - We report the case of a patient who underwent radiotherapy of the neck because of
      an epidermoid carcinoma in Rosenmuller's fossa. Eleven months later, T1-weighted
      brain magnetic resonance imaging (MRI) revealed a bulbo-pontine lesion, and the
      clinical course and sequential MRI results led to a diagnosis of radionecrosis
      induced rhombencephalopathy. At a distance of more than three years, the lesion
      is no longer visible on MRI images but the severe neurological deficits remain.
      The clinical picture has not been improved by treatment with prednisone,
      hyperbaric oxygen, symptomatic therapies or anticoagulants.

PMID- 10933487
TI  - Recurrence of ibuprofen-induced aseptic meningitis in an otherwise healthy
      patient.
AB  - We report the case of a 74-year-old woman who had three episodes of aseptic
      meningitis in a period of 20 years. These episodes always occurred a few hours
      after the assumption of a non-steroidal anti-inflammatory drug (NSAID) per os.
      Nevertheless, the pharmacological anamnesis did not receive proper attention,
      neither the first nor the second time, and the meningeal syndrome with aseptic
      liquor was attributed to a viral aggression. However, when the third episode
      occurred, due to the strict time correlation between the assumption of the drug
      and the occurrence of symptoms, both the results of the liquoral analysis and the
      anamnestic records allowed recognition of ibuprofen as the cause of acute
      meningitis.

PMID- 10933488
TI  - Innervation of the human epidermis. A historical review.
AB  - Skin biopsy represents an attractive technique to evaluate the extensive
      innervation of human epidermis, as demonstrated by the immunoreactivity of the
      intra-epidermal nerve fibers to the marker protein gene product 9.5. Intra
      epidermal nerve fibers can be reliably quantified, and their density correlates
      with both the presence and the severity of sensory neuropathy. The first
      description of nerve fibers within human epidermis was published by Paul
      Langerhans. However, the limitations imposed by the relatively insensitive
      staining methods led several investigators working during the following century
      to deny or minimize their existence. The author reviews the assumptions and the
      striking discrepancies emerging from the wide literature on cutaneous sensory
      terminations since the late nineteenth century and highlights the new
      developments emerging from the most recent works.

PMID- 10933489
TI  - Thromboembolic neurologic events in patients with antiphospholipid-antibody
      syndrome.

PMID- 10933490
TI  - Could flumazenil reverse neurological deficits in acute cerebral ischemia?

PMID- 10933491
TI  - Structural requirements of pyrroloquinoline quinone dependent enzymatic
      reactions.
AB  - On the basis of crystal structures of the pyrroloquinoline quinone (PQQ)
      dependent enzymes methanol dehydrogenase (MDH) and soluble glucose dehydrogenase
      (s-GDH), different catalytic mechanisms have been proposed. However, several
      lines of biochemical and kinetic evidence are strikingly similar for both
      enzymes. To resolve this discrepancy, we have compared the structures of these
      enzymes in complex with their natural substrates in an attempt to bring them in
      line with a single reaction mechanism. In both proteins, PQQ is located in the
      center of the molecule near the axis of pseudo-symmetry. In spite of the absence
      of significant sequence homology, the overall binding of PQQ in the respective
      active sites is similar. Hydrogen bonding interactions are made with polar
      protein side chains in the plane of the cofactor, whereas hydrophobic stacking
      interactions are important below and above PQQ. One Arg side chain and one
      calcium ion are ligated to the ortho-quinone group of PQQ in an identical fashion
      in either active site, in agreement with their proposed catalytic function of
      polarizing the PQQ C5-O5 bond. The substrates are bound in a similar position
      above PQQ and within hydrogen bond distance of the putative general bases Asp297
      (MDH) and His144 (s-GDH). On the basis of these similarities, we propose that MDH
      and s-GDH react with their substrates through an identical mechanism, comprising
      general base-catalyzed hydride transfer from the substrate to PQQ and subsequent
      tautomerization of the PQQ intermediate to reduced PQQ.

PMID- 10933492
TI  - Topography of a 2.0 A structure of alpha1-antitrypsin reveals targets for
      rational drug design to prevent conformational disease.
AB  - Members of the serpin family of serine proteinase inhibitors play important roles
      in the inflammatory, coagulation, fibrinolytic, and complement cascades. An
      inherent part of their function is the ability to undergo a structural
      rearrangement, the stressed (S) to relaxed (R) transition, in which an extra
      strand is inserted into the central A beta-sheet. In order for this transition to
      take place, the A sheet has to be unusually flexible. Malfunctions in this
      flexibility can lead to aberrant protein linkage, serpin inactivation, and
      diseases as diverse as cirrhosis, thrombosis, angioedema, emphysema, and
      dementia. The development of agents that control this conformational
      rearrangement requires a high resolution structure of an active serpin. We
      present here the topology of the archetypal serpin alpha1-antitrypsin to 2 A
      resolution. This structure allows us to define five cavities that are potential
      targets for rational drug design to develop agents that will prevent
      conformational transitions and ameliorate the associated disease.

PMID- 10933493
TI  - NMR structure of a concatemer of the first and second ligand-binding modules of
      the human low-density lipoprotein receptor.
AB  - The ligand-binding domain of the human low-density lipoprotein receptor consists
      of seven modules, each of 40-45 residues. In the presence of calcium, these
      modules adopt a common polypeptide fold with three conserved disulfide bonds. A
      concatemer of the first and second modules (LB(1-2)) folds efficiently in the
      presence of calcium ions, forming the same disulfide connectivities as in the
      isolated modules. The three-dimensional structure of LB(1-2) has now been solved
      using two-dimensional 1H NMR spectroscopy and restrained molecular dynamics
      calculations. No intermodule nuclear Overhauser effects were observed, indicating
      the absence of persistent interaction between them. The near random-coil NH and H
      alpha chemical shifts and the low phi and psi angle order parameters of the four
      residue linker suggest that it has considerable flexibility. The family of LB(1
      2) structures superimposed well over LB1 or LB2, but not over both modules
      simultaneously. LB1 and LB2 have a similar pattern of calcium ligands, but the
      orientations of the indole rings of the tryptophan residues W23 and W66 differ,
      with the latter limiting solvent access to the calcium ion. From these studies,
      it appears that although most of the modules in the ligand-binding region of the
      receptor are joined by short segments, these linkers may impart considerable
      flexibility on this region.

PMID- 10933494
TI  - The active site and substrates binding mode of malonyl-CoA synthetase determined
      by transferred nuclear Overhauser effect spectroscopy, site-directed mutagenesis,
      and comparative modeling studies.
AB  - The active sites and substrate bindings of Rhizobium trifolii molonyl-CoA
      synthetase (MCS) catalyzing the malonyl-CoA formation from malonate and CoA have
      been determined based on NMR spectroscopy, site-directed mutagenesis, and
      comparative modeling methods. The MCS-bound conformation of malonyl-CoA was
      determined from two-dimensional-transferred nuclear Overhauser effect
      spectroscopy data. MCS protein folds into two structural domains and consists of
      16 alpha-helices, 24 beta-strands, and several long loops. The core active site
      was determined as a wide cleft close to the end of the small C-terminal domain.
      The catalytic substrate malonate is placed between ATP and His206 in the MCS
      enzyme, supporting His206 in its catalytic role as it generates reaction
      intermediate, malonyl-AMP. These findings are strongly supported by previous
      biochemical data, as well as by the site-directed mutagenesis data reported here.
      This structure reveals the biochemical role as well as the substrate specificity
      that conservative residues of adenylate-forming enzymes have.

PMID- 10933495
TI  - Optimization of the catalytic properties of Aspergillus fumigatus phytase based
      on the three-dimensional structure.
AB  - Previously, we determined the DNA and amino acid sequences as well as biochemical
      and biophysical properties of a series of fungal phytases. The amino acid
      sequences displayed 49-68% identity between species, and the catalytic properties
      differed widely in terms of specific activity, substrate specificity, and pH
      optima. With the ultimate goal to combine the most favorable properties of all
      phytases in a single protein, we attempted, in the present investigation, to
      increase the specific activity of Aspergillus fumigatus phytase. The crystal
      structure of Aspergillus niger NRRL 3135 phytase known at 2.5 A resolution served
      to specify all active site residues. A multiple amino acid sequence alignment was
      then used to identify nonconserved active site residues that might correlate with
      a given favorable property of interest. Using this approach, Gln27 of A.
      fumigatus phytase (amino acid numbering according to A. niger phytase) was
      identified as likely to be involved in substrate binding and/or release and,
      possibly, to be responsible for the considerably lower specific activity (26.5
      vs. 196 U x [mg protein](-1) at pH 5.0) of A. fumigatus phytase when compared to
      Aspergillus terreus phytase, which has a Leu at the equivalent position. Site
      directed mutagenesis of Gln27 of A. fumigatus phytase to Leu in fact increased
      the specific activity to 92.1 U x (mg protein)(-1), and this and other mutations
      at position 27 yielded an interesting array of pH activity profiles and substrate
      specificities. Analysis of computer models of enzyme-substrate complexes
      suggested that Gln27 of wild-type A. fumigatus phytase forms a hydrogen bond with
      the 6-phosphate group of myo-inositol hexakisphosphate, which is weakened or lost
      with the amino acid substitutions tested. If this hydrogen bond were indeed
      responsible for the differences in specific activity, this would suggest product
      release as the rate-limiting step of the A. fumigatus wild-type phytase reaction.

PMID- 10933496
TI  - A model of troponin-I in complex with troponin-C using hybrid experimental data:
      the inhibitory region is a beta-hairpin.
AB  - We present a model for the skeletal muscle troponin-C (TnC)/troponin-I (TnI)
      interaction, a critical molecular switch that is responsible for calcium
      dependent regulation of the contractile mechanism. Despite concerted efforts by
      multiple groups for more than a decade, attempts to crystallize troponin-C in
      complex with troponin-I, or in the ternary troponin-complex, have not yet
      delivered a high-resolution structure. Many groups have pursued different
      experimental strategies, such as X-ray crystallography, NMR, small-angle
      scattering, chemical cross-linking, and fluorescent resonance energy transfer
      (FRET) to gain insights into the nature of the TnC/TnI interaction. We have
      integrated the results of these experiments to develop a model of the TnC/TnI
      interaction, using an atomic model of TnC as a scaffold. The TnI sequence was fit
      to each of two alternate neutron scattering envelopes: one that winds about TnC
      in a left-handed sense (Model L), and another that winds about TnC in a right
      handed sense (Model R). Information from crystallography and NMR experiments was
      used to define segments of the models. Tests show that both models are consistent
      with available cross-linking and FRET data. The inhibitory region TnI(95-114) is
      modeled as a flexible beta-hairpin, and in both models it is localized to the
      same region on the central helix of TnC. The sequence of the inhibitory region is
      similar to that of a beta-hairpin region of the actin-binding protein profilin.
      This similarity supports our model and suggests the possibility of using an
      available profilin/actin crystal structure to model the TnI/actin interaction. We
      propose that the beta-hairpin is an important structural motif that communicates
      the Ca2+-activated troponin regulatory signal to actin.

PMID- 10933497
TI  - Soft metal ions, Cd(II) and Hg(II), induce triple-stranded alpha-helical assembly
      and folding of a de novo designed peptide in their trigonal geometries.
AB  - We previously reported the de novo design of an amphiphilic peptide
      [YGG(IEKKIEA)4] that forms a native-like, parallel triple-stranded coiled coil.
      Starting from this peptide, we sought to regulate the assembly of the peptide by
      a metal ion. The replacement of the Ile18 and Ile22 residues with Ala and Cys
      residues, respectively, in the hydrophobic positions disrupted of the triple
      stranded alpha-helix structure. The addition of Cd(II), however, resulted in the
      reconstitution of the triple-stranded alpha-helix bundle, as revealed by circular
      dichroism (CD) spectroscopy and sedimentation equilibrium analysis. By titration
      with metal ions and monitoring the change in the intensity of the CD spectra at
      222 nm, the dissociation constant Kd was determined to be 1.5 +/- 0.8 microM for
      Cd(II). The triple-stranded complex formed by the 113Cd(II) ion showed a single
      113Cd NMR resonance at 572 ppm whose chemical shift was not affected by the
      presence of Cl- ions. The 113Cd NMR resonance was connected with the betaH
      protons of the cysteine residue by 1H-113Cd heteronuclear multiple quantum
      correlation spectroscopy. These NMR results indicate that the three cysteine
      residues are coordinated to the cadmium ion in a trigonal-planar complex. Hg(II)
      also induced the assembly of the peptide into a triple-stranded alpha-helical
      bundle below the Hg(II)/peptide ratio of 1/3. With excess Hg(II), however, the
      alpha-helicity of the peptide was decreased, with the change of the Hg(II)
      coordination state from three to two. Combining this construct with other
      functional domains should facilitate the production of artificial proteins with
      functions controlled by metal ions.

PMID- 10933499
TI  - The unfolding enthalpy of the pH 4 molten globule of apomyoglobin measured by
      isothermal titration calorimetry.
AB  - The unfolding enthalpy of the pH 4 molten globule from sperm whale apomyoglobin
      has been measured by isothermal titration calorimetry, using titration to acid
      pH. The unfolding enthalpy is close to zero at 20 degrees C, in contrast both to
      the positive values expected for peptide helices and the negative values reported
      for holomyoglobin and native apomyoglobin. At 20 degrees C, the hydrophobic
      interaction should make only a small contribution to the unfolding enthalpy
      according to the liquid hydrocarbon model. Our result indicates that some factor
      present in the unfolding enthalpies of native proteins makes the unfolding
      enthalpy of the pH 4 molten globule less positive than expected from data for
      peptide helices.

PMID- 10933498
TI  - The dihydrolipoyl acyltransferase (BCE2) subunit of the plant branched-chain
      alpha-ketoacid dehydrogenase complex forms a 24-mer core with octagonal symmetry.
AB  - Little is known of the plant branched-chain alpha-ketoacid dehydrogenase complex.
      We have undertaken a detailed study of the structure of the dihydrolipoyl
      acyltransferase (BCE2) subunit that forms the core of the complex, to which two
      other enzymes attach. Mature Arabidopsis thaliana BCE2 was expressed in
      Escherichia coli. The soluble recombinant protein was purified using a Superose 6
      size-exclusion column to >90% homogeneity and was catalytically active. The
      recombinant protein formed a stable complex with a native molecular mass of 0.95
      MDa and an S coefficient of 19.4, consistent with formation of a 24-mer. Negative
      staining transmission electron microscopy of the recombinant protein confirmed
      that BCE2 forms a core with octagonal symmetry. Despite divergence of mammalian
      and plant BCE2s, there is clearly conservation of structure that is independent
      of primary sequence.

PMID- 10933500
TI  - Bovine beta-lactoglobulin: interaction studies with palmitic acid.
AB  - Bovine beta-lactoglobulin (BLG) in vivo has been found complexed with fatty
      acids, especially palmitic and oleic acid. To elucidate the still unknown
      structure-function relationship in this protein, the interactions between 13C
      enriched palmitic acid (PA) and BLG were investigated by means of one-, two-, and
      three-dimensional NMR spectroscopy in the pH range 8.4-2.1. The NMR spectra
      revealed that at neutral pH the ligand is bound within the central cavity of BLG,
      with the methyl end deeply buried within the protein. The analysis of 13C spectra
      of the holo protein revealed the presence of conformational variability of bound
      PA carboxyl end in the pH range 8.4-5.9, related to the Tanford transition. The
      release of PA starts at pH lower than 6.0, and it is nearly complete at acidic
      pH. This finding is relevant in relation to the widely reported hypothesis that
      this protein can act as a transporter through the acidic gastric tract. Ligand
      binding and release is shown to be completely reversible over the entire pH range
      examined, differently from other fatty acid binding proteins whose behavior is
      analyzed throughout the paper. The mode of interaction of BLG is compatible with
      the proposed function of facilitating the digestion of milk fat during the
      neonatal period of calves.

PMID- 10933501
TI  - Autopalmitoylation of tubulin.
AB  - Pure rat brain tubulin is readily palmitoylated in vitro using [3H]palmitoyl CoA
      but no added enzymes. A maximum of approximately six palmitic acids are added per
      dimer in 2-3 h at 36-37 degrees C under native conditions. Both alpha and beta
      tubulin are labeled, and 63-73% of the label was hydroxylamine-labile, presumed
      thioesters. Labeling increases with increasing pH and temperature, and with low
      concentrations of guanidine HCl or KCl (but not with urea) to a maximum of
      approximately 13 palmitates/dimer. High SDS and guanidine HCl concentrations are
      inhibitory. At no time could all 20 cysteine residues of the dimer be
      palmitoylated. Polymerization to microtubules, or use of tubulin S, markedly
      decreases the accessibility of the palmitoylation sites. Palmitoylation increases
      the electrophoretic mobility of a portion of alpha tubulin toward the beta band.
      Palmitoylated tubulin binds a colchicine analogue normally, but during three
      warm/cold polymerization/depolymerization cycles there is a progressive loss of
      palmitoylated tubulin, indicating decreased polymerization competence. We
      postulate that local electrostatic factors are major regulators of reactivity of
      tubulin cysteine residues toward palmitoyl CoA, and that the negative charges
      surrounding a number of the cysteines are sensitive to negative charges on
      palmitoyl CoA.

PMID- 10933503
TI  - The X-ray structure of the NAD-dependent 5,10-methylenetetrahydrofolate
      dehydrogenase from Saccharomyces cerevisiae.
AB  - Eucaryotes possess one or more NADP-dependent methylene-THF dehydrogenases as
      part of multifunctional enzymes. In addition, yeast expresses an unusual
      monofunctional NAD-dependent enzyme, yMTD. We report X-ray structures for the
      apoenzyme and its complex with NAD+ at 2.8 and 3.0 A resolution, respectively.
      The protein fold resembles that seen for the human and Escherichia coli
      dehydrogenase/cyclohydrolase bifunctional enzymes. The enzyme has two prominent
      domains, with the active site cleft between them. yMTD has a noncanonical NAD
      binding domain that has two inserted strands compared with the NADP-binding
      domains of the bifunctional enzymes. This insert precludes yMTD from dimerizing
      in the same way as the bifunctional enzymes. yMTD functions as a dimer, but the
      mode of dimerization is novel. It does not appear that the difference in
      dimerization accounts for the difference in cofactor specificity or for the loss
      of cyclohydrolase activity. These functional differences are probably accounted
      for by minor differences within the tertiary structure of the active site of the
      monomeric protein.

PMID- 10933502
TI  - The disulfide bond pattern of catrocollastatin C, a disintegrin-like/cysteine
      rich protein isolated from Crotalus atrox venom.
AB  - The disulfide bond pattern of catrocollastatin-C was determined by N-terminal
      sequencing and mass spectrometry. The N-terminal disintegrin-like domain is a
      compact structure including eight disulfide bonds, seven of them in the same
      pattern as the disintegrin bitistatin. The protein has two extra cysteine
      residues (XIII and XVI) that form an additional disulfide bond that is
      characteristically found in the disintegrin-like domains of cellular
      metalloproteinases (ADAMs) and PIII snake venom Zn-metalloproteinases (SVMPs).
      The C-terminal cysteine-rich domain of catrocollastatin-C contains five disulfide
      bonds between nearest-neighbor cysteines and a long range disulfide bridge
      between CysV and CysX. These results provide structural evidence for a
      redefinition of the disintegrin-like and cysteine-rich domain boundaries. An
      evolutionary pathway for ADAMs, PIII, and PII SVMPs based on disulfide bond
      engineering is also proposed.

PMID- 10933504
TI  - HYR, an extracellular module involved in cellular adhesion and related to the
      immunoglobulin-like fold.
AB  - Domains belonging to the immunoglobulin-like fold are responsible for a wide
      variety of molecular recognition processes. Here we describe a new family of
      domains, the HYR family, which is predicted to belong to this fold, and which
      appears to be involved in cellular adhesion. HYR domains were identified in
      several eukaryotic proteins, often associated with Complement Control Protein
      (CCP) modules or arranged in multiple copies. Our analysis provides a sequence
      and structural basis for understanding the role of these domains in interaction
      mechanisms and leads to further characterization of heretofore undescribed
      repeated domains with similar folds found in several bacterial proteins involved
      in enzymatic activities (some chitinases) or in cell surface adhesion
      (streptococcal C-alpha antigen).

PMID- 10933505
TI  - Structure of a protein G helix variant suggests the importance of helix
      propensity and helix dipole interactions in protein design.
AB  - Six helix surface positions of protein G (Gbeta1) were redesigned using a
      computational protein design algorithm, resulting in the five fold mutant
      Gbeta1m2. Gbeta1m2 is well folded with a circular dichroism spectrum nearly
      identical to that of Gbeta1, and a melting temperature of 91 degrees C,
      approximately 6 degrees C higher than that of Gbeta1. The crystal structure of
      Gbeta1m2 was solved to 2.0 A resolution by molecular replacement. The absence of
      hydrogen bond or salt bridge interactions between the designed residues in
      Gbeta1m2 suggests that the increased stability of Gbeta1m2 is due to increased
      helix propensity and more favorable helix dipole interactions.

PMID- 10933506
TI  - Charge-charge interactions influence the denatured state ensemble and contribute
      to protein stability.
AB  - Several recent studies have shown that it is possible to increase protein
      stability by improving electrostatic interactions among charged groups on the
      surface of the folded protein. However, the stability increases are considerably
      smaller than predicted by a simple Coulomb's law calculation, and in some cases,
      a charge reversal on the surface leads to a decrease in stability when an
      increase was predicted. These results suggest that favorable charge-charge
      interactions are important in determining the denatured state ensemble, and that
      the free energy of the denatured state may be decreased more than that of the
      native state by reversing the charge of a side chain. We suggest that when the
      hydrophobic and hydrogen bonding interactions that stabilize the folded state are
      disrupted, the unfolded polypeptide chain rearranges to compact conformations
      with favorable long-range electrostatic interactions. These charge-charge
      interactions in the denatured state will reduce the net contribution of
      electrostatic interactions to protein stability and will help determine the
      denatured state ensemble. To support this idea, we show that the denatured state
      ensemble of ribonuclease Sa is considerably more compact at pH 7 where favorable
      charge-charge interactions are possible than at pH 3, where unfavorable
      electrostatic repulsion among the positive charges causes an expansion of the
      denatured state ensemble. Further support is provided by studies of the ionic
      strength dependence of the stability of charge-reversal mutants of ribonuclease
      Sa. These results may have important implications for the mechanism of protein
      folding.

PMID- 10933507
TI  - Decoys 'R' Us: a database of incorrect conformations to improve protein structure
      prediction.
AB  - The development of an energy or scoring function for protein structure prediction
      is greatly enhanced by testing the function on a set of computer-generated
      conformations (decoys) to determine whether it can readily distinguish native
      like conformations from nonnative ones. We have created "Decoys 'R' Us," a
      database containing many such sets of conformations, to provide a resource that
      allows scoring functions to be improved.

PMID- 10933508
TI  - Structural effects of the active site mutation cysteine to serine in Bacillus
      cereus zinc-beta-lactamase.
AB  - Beta-lactamases are involved in bacterial resistance. Members of the metallo
      enzyme class are now found in many pathogenic bacteria and are becoming thus of
      major clinical importance. Despite the availability of Zn-beta-lactamase X-ray
      structures their mechanism of action is still unclear. One puzzling observation
      is the presence of one or two zincs in the active site. To aid in assessing the
      role of zinc content in beta-lactam hydrolysis, the replacement by Ser of the
      zinc-liganding residue Cys168 in the Zn-beta-lactamase from Bacillus cereus
      strain 569/H/9 was carried out: the mutant enzyme (C168S) is inactive in the mono
      Zn form, but active in the di-Zn form. The structure of the mono-Zn form of the
      C168S mutant has been determined at 1.85 A resolution. Ser168 occupies the same
      position as Cys168 in the wild-type enzyme. The protein residues mostly affected
      by the mutation are Asp90-Arg91 and His210. A critical factor for the activity of
      the mono-Zn species is the distance between Asp90 and the Zn ion, which is
      controlled by Arg91: a slight movement of Asp90 impairs catalysis. The evolution
      of a large superfamily including Zn-beta-lactamases suggests that they may not
      all share the same mechanism.

PMID- 10933509
TI  - Mesoscopic surfactant organization and membrane protein crystallization.
AB  - The paucity of detailed X-ray crystallographic structures of integral membrane
      proteins arises from substantive technical obstacles in the overexpression of
      multimilligram quantities of protein, and in the crystallization of purified
      protein-detergent complexes (PDCs). With rare exception, crystal contacts within
      the lattice are mediated by protein-protein interaction, and the detergent
      surrounding the protein behaves as a disordered solvent. The addition and use of
      surfactants that display mesoscopic self-assembly behavior in membrane protein
      crystallization experiments presents a novel alternative strategy. Well-ordered
      crystals of the water channel human aquaporin-1 (hAQP1) that diffract to 4 A
      resolution have been obtained with this approach.

PMID- 10933510
TI  - Folding of a three-stranded coiled coil.
AB  - Coiled coils consist of two or more amphipathic a-helices wrapped around each
      other to form a superhelical structure stabilized at the interhelical interface
      by hydrophobic residues spaced in a repeating 3-4 sequence pattern. Dimeric
      coiled coils have been shown to often form in a single step reaction in which
      association and folding of peptide chains are tightly coupled. Here, we ask
      whether such a simple folding mechanism may also apply to the formation of a
      three-stranded coiled coil. The designed 29-residue peptide LZ16A was shown
      previously to be in a concentration-dependent equilibrium between unfolded
      monomer (M), folded dimer (D), and folded trimer (T). We show by time-resolved
      fluorescence change experiments that folding of LZ16A to D and T can be described
      by 2M (k1)<==>(k(-1)) D and M + D (k2)<==>(k(-2)) T. The following rate constants
      were determined (25 degrees C, pH 7): k1 = 7.8 x 10(4) M(-1) s(-1), k(-1) = 0.015
      s(-1), k2 = 6.5 x 10(5) M(-1) s(-1), and k(-2) = 1.1 s(-1). In a separate
      experiment, equilibrium binding constants were determined from the change with
      concentration of the far-ultraviolet circular dichroism spectrum of LZ16A and
      were in good agreement with the kinetic rate constants according to K(D) = k1/2k(
      1) and K(T) = k2/k(-2). Furthermore, pulsed hydrogen-exchange experiments
      indicated that only unfolded M and folded D and T were significantly populated
      during folding. The results are compatible with a two-step reaction in which a
      subpopulation of association competent (e.g., partly helical) monomers associate
      to dimeric and trimeric coiled coils.

PMID- 10933511
TI  - van't Hoff enthalpies without baselines.
AB  - Analysis of thermal melting curves represents one important approach for
      evaluating protein stability and the consequences of amino acid substitution on
      protein structure. By use of the van't Hoff relationship, the differential
      melting curve can be robustly fit to only three parameters, two of which are the
      underlying physical constants of melting temperature (Tm) and van't Hoff enthalpy
      (deltaHvH). Calculated Tm and deltaHvH values are insensitive to the choice of
      pre- and post-transition baselines. Consequently, the method accurately computes
      Tm and deltaHvH for extremely truncated data sets, in the complete absence of
      baseline information, and for proteins with low melting temperatures, where the
      traditional direct approach routinely fails. Moreover, agreement between deltaHvH
      values obtained using points derived from pre- vs. post-transition data provide
      an independent method for detecting some classes of non-two-state transitions.
      Finally, fitting of the differential denaturation curve should prove useful for
      analysis of abbreviated data sets obtained from high throughput array analysis of
      protein stability.

PMID- 10933512
TI  - Cyclo-oxygenase-2 inhibitors: rationale and therapeutic potential for Alzheimer's
      disease.
AB  - The newly introduced cyclo-oxygenase-2 (COX-2) inhibiting nonsteroidal anti
      inflammatory drugs (NSAIDs) have been established as effective agents in treating
      arthritic conditions, while greatly reducing the gastrointestinal adverse effects
      of traditional NSAIDs. There are expectations that NSAIDs will be useful in the
      treatment of Alzheimer's disease (AD), and that COX-2 inhibitors might have a
      role. However, a recently reported clinical trial of a COX-2 inhibitor in AD
      indicated that it was neither protective nor did it accelerate the decline. The
      expectations were based on pathological evidence of inflammatory changes
      associated with AD lesions and epidemiological evidence of a reduced prevalence
      of AD in populations taking NSAIDs. They were supported by preliminary evidence
      showing efficacy of NSAIDs in treating patients with AD. These data are based on
      the use of traditional NSAIDs. Whether COX-2 inhibitors would be similarly
      effective was uncertain since COX-2 is constitutively expressed in neurons.
      Animal experiments suggest that COX-2 may be performing adaptive functions
      associated with normal neurons and protective functions associated with stressed
      neurons. These results emphasise that the appropriate target for NSAID trials in
      AD is COX-1, but they also indicate that there would be no contraindication to
      the use of those traditional NSAIDs which have mixed COX-1/COX-2 inhibiting
      activity.

PMID- 10933516
TI  - Application of chrome azurol S for the extractive spectrophotometric
      determination of fluoxetine and fluvoxamine.
AB  - Chrome azurol S has been tested as a spectrophotometric reagent for the
      determination of fluoxetine (FXT) and fluvoxamine (FXM). It reacts in aqueous
      media with FXT and FXM forming coloured, sparingly soluble in water compounds.
      These compounds can be quantitatively extracted with some organic solvents. This
      property has been exploited for the development of the extractive
      spectrophotometric methods for the determination of fluoxetine and fluvoxamine.

PMID- 10933513
TI  - Drug therapy for gynaecological cancer in older women.
AB  - A substantial proportion of all women dying from gynaecological malignancies are
      aged >75 years. Many reports have indicated that the survival of these patients
      is decreased compared with younger patients. Differences in biological behaviour,
      stage of the disease at presentation, and reluctance to undergo aggressive
      treatment with its associated morbidity are among the factors thought to be
      responsible for this difference in outcomes. However, investigations also
      indicate that elderly patients may receive less surgical and chemotherapeutic
      treatment without obvious clinical rationale. This overview is aimed at providing
      a guideline of chemotherapy appropriate for patients with epithelial ovarian,
      uterine (corpus and cervix), and vulvar cancer, aged 70 to 75 years and over.
      Platinum-based chemotherapy is the cornerstone of drug treatment in patients with
      ovarian cancer. Patients aged between 70 and 75 years with a good performance
      status can be treated with cisplatin- or carboplatin-based chemotherapy.
      Carboplatin, either in combination or as a single-agent, may offer advantages in
      patients aged >75 years and in those with a poor performance status. For patients
      with early recurrence there is no standard treatment, but several cytostatic and
      hormonal agents can be used with palliative intent. Patients with a late
      recurrence are probably best retreated with a platinum-based regimen. In
      metastatic endometrial cancer, hormonal therapy is the first choice in tumours
      expressing a progesterone receptor. Poorly differentiated tumours infrequently
      respond to endocrine therapy. In this situation, and for patients with tumours
      that have become resistant to hormonal manipulation, platinum-based chemotherapy
      may be used. The use of carboplatin-based regimens seems preferable in elderly
      patients, particularly in those with a decreased performance status. The
      usefulness of chemotherapy in elderly patients with cervical cancer is limited.
      In case of recurrent or metastatic disease, the use of single agent (low-dose)
      cisplatin should be balanced against best supportive care. Although overall
      chemoradiation seems superior than radiotherapy alone in patients with locally
      advanced cervical cancer, the feasibility of this approach in elderly patients
      needs further investigation. Chemoradiation might also be considered in patients
      with locally advanced vulvar cancer. However, treatment-related morbidity can be
      considerable and randomised studies are lacking to prove a survival benefit. Our
      understanding of the tolerance and effectiveness of chemotherapy in elderly
      patients is still incomplete due to a paucity of trials that specifically focus
      on this subset of patients. However, there appears no argument to withhold
      chemotherapy based purely on age.

PMID- 10933517
TI  - Indirect determination of captopril by AAS.
AB  - An indirect method is described for the determination of captopril (KPL) in
      pharmaceutical preparations by atomic absorption spectrometry (AAS). The
      procedure is based on the complexation of KPL with an excess of Pd(II) ion. The
      unreacted Pd(II) was resoluted on a cationic ion-exchanger resin, while Pd(II)
      KPL sequestrate was not retained. The effluent Pd(II) sequestrade was measured by
      AAS. The absorbance is found to increase linearly with increasing KPL
      concentration, because the amount of Pd(II) is related to the concentration of
      KPL, which is corroborate by the calculated correlation coefficient value of
      0.9939. The system obeys Beer's law for 1-40 microg ml(-1), S.D. was found to be
      0.039 (n = 5). The Pd(II)-KPL complex was obtained in the solid phase.
      Characterization of the complex was performed by elemental analysis, TG,
      conductance measurements and IR, 1H-NMR spectroscopy.

PMID- 10933518
TI  - Assay of ephedrine hydrochloride and theophylline in pharmaceutical formulations
      by differential-derivative spectroscopy.
AB  - Rapid and accurate binary mixture resolution of ephedrine hydrochloride and
      theophylline was performed. Differential-derivative spectrophotometry with a zero
      crossing measurement technique was used for the quantitative determination of
      ephedrine hydrochloride and theophylline in pharmaceuticals. Neither sample
      pretreatment nor separation were required. Linear calibration graphs of
      differential first derivative values (at 262.4 and 256.3 nm for theophylline and
      ephedrine hydrochloride, respectively) versus concentration (in the ranges 6.0
      40.0 and 100.0-1000.0 microg ml(-1) for theophylline and ephedrine hydrochloride,
      respectively) were obtained with negligible intercepts. Vierordt's method was
      also developed for a comparison method. Commercial tablet and laboratory-prepared
      mixtures containing both drugs were assayed using the developed methods. Both
      methods showed good linearity, precision and reproducibility.

PMID- 10933514
TI  - The relationship between cholesterol and stroke: implications for
      antihyperlipidaemic therapy in older patients.
AB  - Various studies on the relationship between serum cholesterol level and the risk
      of stroke have been published recently. Subsequent reviews have extrapolated
      information on stroke from the clinical trials originally aimed at lowering
      cholesterol for the primary and secondary prevention of myocardial infarction
      (MI) in middle-aged patients. We have reviewed the epidemiological knowledge on
      the relationship between serum cholesterol levels and stroke, and also focused on
      possible reduction of the risk of stroke with hydroxymethylglutaryl coenzyme A
      (HMG-CoA) reductase inhibitor treatment. Possible benefits from such therapy are
      particularly relevant for the elderly population which is at particularly high
      risk for stroke. The effects of serum cholesterol levels on the risk for
      haemorrhagic and ischaemic stroke have been evaluated. Indirect epidemiological
      evidence indicates that serum levels of total cholesterol and its subfractions
      are determinants of stroke, but their associations are relatively weak. When
      exploring the possible association of serum cholesterol levels with the increased
      risk of stroke with aging, we concluded that, as in younger adults, elevated
      total cholesterol and decreased high density lipoprotein-cholesterol levels
      predispose to ischaemic stroke in the elderly. The mechanism through which serum
      cholesterol levels increase stroke risk is based on its actions on the artery
      walls. Indirect evidence suggests that the reduction in the stroke risk with HMG
      CoA reductase inhibitors is larger than would be expected with reduction of
      elevated serum cholesterol level alone. Therefore, antioxidant and endothelium
      stabilising properties of HMG-CoA reductase inhibitors may contribute in reducing
      the risk of stroke in recipients. Lowering high serum cholesterol with HMG-CoA
      reductase inhibitors has been beneficial in the primary and secondary prevention
      of MI. No trials have specifically tested the effect of cholesterol lowering with
      HMG-CoA reductase inhibitors on stroke occurrence. High serum cholesterol levels
      are a risk factor for ischaemic stroke, although the risk imparted is lower than
      that for MI. Although the relative risk of stroke associated with elevated serum
      cholesterol levels is only moderate, its population attributable risk is high
      given the increase in the elderly population worldwide. The effect of cholesterol
      reduction with HMG-CoA reductase inhibitors on prevention of ischaemic stroke
      should be evaluated in prospective, randomised, placebo-controlled trials in the
      elderly. The tolerability of lipid-lowering drugs in the elderly and the cost
      effectiveness of primary prevention of stroke using lipid-lowering drugs also
      needs to be assessed in the elderly.

PMID- 10933515
TI  - Docetaxel: a review of its use in non-small cell lung cancer.
AB  - Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents,
      is effective in the treatment of patients with locally advanced and metastatic
      non-small cell lung cancer (NSCLC). In noncomparative trials in patients with
      NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38%
      and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan,
      docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously
      untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher
      response rates than either vinorelbine or ifosfamide in previously treated
      patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year
      survival rate compared with those who received vinorelbine or ifosfamide.
      Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that
      are similar to those reported for most platinum-containing standard combinations
      such as cisplatin plus vinorelbine. Combination of docetaxel with one other
      antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy
      naive patients; triple chemotherapy combinations produced responses in 51 and 60%
      of patients. Promising results from a few small studies and one large phase II
      study have also indicated a potential role for docetaxel as neoadjuvant therapy.
      The main dose-limiting adverse event associated with docetaxel is neutropenia,
      and fluid retention is common in many patients. The tolerability profile is
      generally acceptable in the majority of patients, although extra care has to be
      taken in patients with impaired liver function to minimise the risk of severe or
      febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by
      patients receiving treatment for locally advanced and metastatic NSCLC, and
      produces response and survival rates equivalent to many current standard
      treatment options. Comparative studies have shown that docetaxel monotherapy
      provides significant survival benefits over best supportive care or treatment
      with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel
      monotherapy are particularly encouraging in patients refractory or resistant to
      cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant
      docetaxel has produced improved survival compared with local treatment alone.
      Combinations of docetaxel with other antineoplastic agents have produced
      relatively high response and 1-year survival rates; however, further comparative
      studies are required to confirm these benefits. In the meantime, docetaxel is a
      welcome addition to the options available for patients with advanced NSCLC.

PMID- 10933519
TI  - Study on electrooxidation of cefadroxil monohydrate and its determination by
      differential pulse voltammetry.
AB  - In this work electrooxidation of cefadroxil monohydrate was investigated using a
      glassy carbon electrode depending on pH and supporting electrolyte. It was shown
      that the direct determination of the substance from capsules and in oral
      suspension could be made by differential pulse voltammetry (DPV). UV and first
      derivative UV spectrophotometric methods are also proposed as comparative
      methods.

PMID- 10933520
TI  - A rapid high performance liquid chromatographic (HPLC) assay for the
      determination of oxytetracycline in commercial pharmaceuticals.
AB  - In the present study, a simple, sensitive and rapid reversed-phase high
      performance liquid chromatographic (HPLC) method with ultraviolet detection for
      the analysis of oxytetracycline (OTC) is developed and applied to the
      determination of the antibiotic in commercial pharmaceutical preparations
      (powder, capsules, vaginal tablets and ointment). The isocratic elution is
      performed with methanol-0.01 M oxalic acid, pH 3.0 (30:70, v/v) at a flow rate of
      0.95 ml min, using a Silasorb C8 analytical column, 250 x 4 mm, 10 microm.
      Codeine is used as internal standard. Absorbance is monitored at 250 nm where
      both analyte of interest and internal standard have significant absorption. Total
      analysis time was approximately 7 min. Data with respect to precision and
      accuracy and limits of detection are reported and discussed. The described method
      can be readily utilised for analysis of pharmaceutical products and
      pharmacokinetic studies as well.

PMID- 10933521
TI  - Use of mixed anhydrides for the determination of terfenadine in dosage forms and
      spiked human plasma.
AB  - Terfenadine reacts with mixed anhydrides (malonic and acetic anhydrides)
      producing a yellow-coloured product with intense fluorescence. Based on this
      fact, a spectrophotometric method was developed for the determination of
      terfenadine in dosage forms. The relation between the absorbance at 395 nm and
      the concentration is rectilinear over the range 0.5-5 microg ml(-1) (molar
      absorptivity is 1.405 x 10(5) l mol(-1) cm (-1)). The reaction product was also
      measured spectrofluorimetrically at 435 nm after excitation at 395 nm. The
      fluorescence intensity was directly proportional to the concentration over the
      range 0.5-4 ng ml(-1) with minimum detectability (S/N = 2) of 0.07 microg ml(-1)
      (approximately 1.5 x 10(-10) M). The different parameters affecting the
      development and stability of the reaction product were carefully studied and
      incorporated into the procedure. The proposed spectrophotometric method was
      successfully applied to the determination of terfenadine in tablets and
      suspensions; the percentage recoveries were 99.83 +/- 0.75 and 99.65 +/- 0.83,
      respectively. The proposed spectrofluorimetric method was applied to the
      determination of terfenadine in spiked human plasma. The percentage recovery was
      99.35 +/- 2.19. The method is highly sensitive and specific. No interference was
      noticed from co-formulated drugs, such as pseudoephedrine and ibuprofen.

PMID- 10933522
TI  - Development and optimisation of a flow injection assay for fluticasone propionate
      using an asymmetrical design and the variable-size simplex algorithm.
AB  - A flow injection analysis method is described to determine fluticasone
      propionate, based upon a novel adaptation of the reaction of o-phthalaldehyde
      with a thiol and a primary amine. The method, which allows both UV and
      fluorescence detection, has been optimised using experimental design. First a
      screening is executed to select the significant factors and in a second step
      these factors are optimised with the variable-size simplex algorithm. In the
      screening step, a two-level fractional factorial design is compared with an
      asymmetrical design containing the same number of experiments, but in which one
      factor is at three levels. It was found that in both designs the same significant
      variables are detected for the two-level factors, but that for the three-level
      factor the asymmetrical design confirms an expectation of having a (local)
      optimum in the examined domain, whilst from the two-level design this is not at
      all apparent. Complete optimisation was carried out for both UV and fluorescence
      detection. The two detection methods did not have the same significant variables.
      For the UV detection, the temperature and the pH adjustment on-line
      (concentration of sodium hydroxide and amount of boric acid) were the most
      critical parameters. For the fluorimetric detection the temperature and the
      fraction of methanol were critical. Moreover the conditions found to be optimal
      are different for both detection methods.

PMID- 10933523
TI  - Determination of cefaclor by selective sample enrichment/clean-up on silica gel
      bonded polyelectrolyte in ion-exchange column chromatography.
AB  - A silica gel-bound cationic polyelectrolyte, poly[N-chloranil N,N,N',N'-
      tetramethylethylene diammonium dichloride], modified as ion-exchanger capable of
      molecular recognition of beta-lactam antibiotic, was used in solid phase
      extraction through column chromatography for a sample clean-up and enrichment of
      analyte from a dilute solution. The optimum and selective sorption conditions for
      a model antibiotic, cefaclor, were established. The high selectivity of polymer
      at pH 9.5 and flow rate as high as 5 ml/min were observed for the quantitative
      sorption of cefaclor. The desorption by 0.1 N HCl at flow rate of 0.1 ml/min and
      subsequent heating at 80 degrees C for 2 h allowed the antibiotic to be detected
      as corresponding oxazolone form in UV-spectrophotometric and differential pulse
      adsorptive stripping voltammetric measurements. The potential of the suggested
      approach was illustrated by estimating cefaclor in urine and blood plasma
      samples.

PMID- 10933524
TI  - Improved high-performance liquid chromatographic method for analysis of L
      carnitine in pharmaceutical formulations.
AB  - A reversed-phase high performance liquid chromatographic method for analysis of L
      carnitine is described. The improved method is able to provide a high resolution
      between L-carnitine and crotonoylbetaine, a major impurity and degradation
      product, and suitable for quantitative analysis of L-carnitine in pharmaceutical
      formulations, such as solution, tablets, and capsules. The resolution, linearity,
      accuracy and reproducibility of the method are discussed.

PMID- 10933525
TI  - Direct-injection LC-MS-MS method for high-throughput simultaneous quantitation of
      simvastatin and simvastatin acid in human plasma.
AB  - A direct-injection liquid chromatography-mass spectrometry-mass spectrometry (LC
      MS-MS) method was developed and validated for the simultaneous quantitation in
      human plasma of the widely used cholesterol-lowering prodrug simvastatin and its
      in vivo generated active drug, simvastatin acid. The plasma samples were injected
      into the LC-MS-MS system after simply adding the internal standard solution in an
      aqueous buffer and centrifuging. The analytes in the buffered plasma samples were
      found to be stable for at least 24 h at 4 degrees C. The method was successfully
      validated under the challenging condition of using a large number of quality
      control (QC) samples including those in which the ratio of the simvastatin
      concentration to the simvastatin acid concentration was different from the
      concentration ratio in the calibration curve standards. Under the dual
      stabilizing conditions of lower temperature (4 degrees C) and lower plasma pH of
      4.9, the in-process hydrolysis of simvastatin to simvastatin acid or the
      lactonization of simvastatin acid to simvastatin was minimized to < or = 1.0%.
      Although the entire run time for on-line cleanup and analysis was only 2.5 min,
      chromatographic base-line separation of simvastatin from simvastatin acid, which
      was required to avoid the interference by simvastatin acid with the simvastatin
      selected reaction monitoring channel, was achieved. The desired lower limit of
      quantitation of 0.5 ng/ml was achieved by injecting only an equivalent of 8.0
      microl of the plasma sample. The extraction column lasted for at least 500
      injections.

PMID- 10933527
TI  - Rapid liquid chromatographic method for simultaneous determination of
      tetracyclines antibiotics and 6-epi-doxycycline in pharmaceutical products using
      porous graphitic carbon column.
AB  - A rapid and selective high performance liquid chromatographic (HPLC) method has
      been developed for the separation and determination of five commercially used
      tetracyclines. The chromatography was performed on a porous graphitic carbon
      (PGC) column, using 0.05 M potassium phosphate buffer (pH 2.0)--acetonitrile (40
      + 60) as the mobile phase and ultraviolet detection at 268 nm. The method permits
      the simultaneous determination of oxytetracycline, metacycline, chlortetracycline
      and doxycycline as well as the separation of one of their common impurities (6
      Epi-doxycycline) in bulk powder and pharmaceutical preparations with detection
      limits of 0.5-2 microg ml(-1) and recoveries of 98.9-100.5%. Correlation
      coefficients for calibration curves in the range of 5-50 microg ml(-1) were
      greater than 0.999 for all tetracyclines. The within- and between-day precision
      was determined for both retention times and peak area. It is suggested that the
      proposed HPLC-PGC method should be used for routine quality control and dosage
      form assay of tetracyclines in pharmaceutical preparations. The chromatographic
      behaviour of the five tetracyclines was examined under variable mobile phase
      compositions, the results revealed that elution order and selectivity were
      dependent on the buffer agent used. Comparison between retentions obtained with
      PGC and with silica-based stationary phase (ODS), showed similar variations of
      the capacity factors with the mobile phase composition, but with a different
      elution order.

PMID- 10933526
TI  - First-derivative spectrophotometric and LC determination of cefuroxime and
      cefadroxil in urine.
AB  - Two methods are presented for the determination of cefuroxime and cefadroxil in
      human urine using first (1D) derivative spectrophotometry and high-performance
      liquid chromatography. Cefuroxime and cefadroxil were determined by measurement
      of their first-derivative amplitude in 0.1 N sodium hydroxide at 292.5 and 267.3
      nm, respectively in the concentration range of 2-10 microg ml(-1) for each drug.
      The HPLC method depends upon using a LiChrospher 100 RP-18 (5 microm) column at
      ambient temperature for cefuroxime and 35 degrees C for cefadroxil with mobile
      phases consisting of water-acetonitrile-acetic acid (85:15:0.1 v/v) at a flow
      rate of 1.5 ml min(-1) for cefuroxime; and 0.02 M potassium dihydrogen phosphate
      acetonitrile (95:5 v/v) containing 0.003% (w/v) hexanesulphonic acid sodium salt
      and adjusted to apparent pH 3 with phosphoric acid at a flow rate of 2 ml min(-1)
      for cefadroxil. Quantitation was achieved with UV detection at 275 and 260 nm for
      cefuroxime and cefadroxil, respectively, based on peak area with linear
      calibration curves at the concentration ranges of 2-10 microg ml(-1) for
      cefuroxime and 5-20 microg ml(-1) for cefadroxil. The proposed methods were
      applied to the determination of dissolution rate for tablets and capsules
      containing each drug. The urinary excretion patterns as the cumulative amounts
      excreted have been calculated for each drug using the proposed methods.

PMID- 10933529
TI  - Determination of bile acids in pharmaceutical formulations using micellar
      electrokinetic chromatography.
AB  - A micellar electrokinetic chromatography method (MEKC) has been developed and
      validated for the determination of bile acids (BA) such as ursodeoxycholic acid
      (UDCA), dehydrocholic acid (DHCA) and deoxycholic acid (DCA) in pharmaceuticals
      for quality control purpose. The background electrolyte consisted of 20 mM borate
      phosphate buffer containing 50 mM sodium dodecylsulfate (SDS), and acetonitrile
      as additive. UV detection was set at 185 nm. Selectivity, linearity, range,
      repeatability, intermediate precision and accuracy showed good results.
      Comparison of the values obtained by MEKC and HPLC methods were in close
      agreement.

PMID- 10933530
TI  - Spectrophotometric studies and application of imipramine-eriochrome cyanine R
      system for determination of imipramine in pharmaceuticals.
AB  - Eriochrome cyanine R (ECR) has been tested as reagent for the determination of
      imipramine. It reacts in neutral medium with imipramine forming reddish compound,
      which can be quantitatively extracted into n-butanol. This property has been
      successfully used for the extractive-spectrophotometric determination of
      imipramine. Beer's law is obeyed in concentration range of 10-80 microg ml(-1) of
      imipramine. The method was applied to the determination of imipramine in its
      pharmaceutical.

PMID- 10933528
TI  - Determination of slime-producing S. epidermidis specific antibodies in human
      immunoglobulin preparations and blood sera by an enzyme immunoassay: correlation
      of antibody titers with opsonic activity and application to preterm neonates.
AB  - Slime-producing Staphylococcus epidermidis is responsible for severe infections
      in immunocompromised patients and, particularly, in premature infants who are
      transiently deficient in IgG. A sulfated polysaccharide with molecular mass of 20
      kDa (20-kDa PS) has been recognized as the major polysaccharide component and
      antigenic determinant of S. epidermidis extracellular slime layer. The presence
      of adequate amounts of antibodies to 20-kDa PS in patients' sera would be of
      importance to prevent or treat slime-producing S. epidermidis bacteremia.
      Administration of intravenous immunoglobulin (IVIG) is considered to be a
      reasonable IgG replacement therapy and has been widely used to prevent or treat
      neonatal sepsis. Clinical trials have shown conflicting results on the efficacy
      of IVIGs and this phenomenon has been attributed to the variability of IVIG
      preparations in the content and opsonic activity of IgG against microorganisms of
      clinical importance. Monitoring of antibodies to distinct bacterial
      macromolecules, which are species-specific and responsible for bacterial
      infections, has not been performed previously. A highly precise and repeatable
      enzyme immunoassay was developed to determine quantitatively the levels of
      antibodies against the 20-kDa PS of S. epidermidis slime. The amount of 20-kDa PS
      specific antibodies found in 27 lots of an IVIG preparation (Sandoglobulin)
      correlated well with their in vitro opsonic activity against slime-producing S.
      epidermidis. The majority of lots (75%) having titers higher than 200 units/ml
      showed significant opsonic activity (50-75%) towards slime-producing S.
      epidermidis. Sandoglobulin lots with titers higher than 200 units/ml of 20-kDa PS
      specific IgG were administered as a prophylactic agent to low-birth weight (lower
      than 1700 g) preterm neonates immediately after birth. The levels of total and 20
      kDa PS specific IgG in neonates' blood sera were significantly higher than those
      found in the control group, even 10 days after the last infusion. The rate of
      slime-producing S. epidermidis bacteremia in neonates who received IVIG was also
      considerably lower than those in the control group. The results of this study
      suggest that specific IgG titers estimated by the developed enzyme immunoassay
      may well be indicative of the IVIG opsonic activity against slime-producing S.
      epidermidis. Furthermore, administration of Sandoglobulin with titers higher than
      a cut-off value of 200 units/ml may significantly protect preterm neonates
      against slime-producing S. epidermidis bacteremia.

PMID- 10933531
TI  - Determination of divalent carboxylic acids in traditional Chinese herbal and
      patent medicines using HPLC with double cell quartz crystal detector.
AB  - A rapid, simple and sensitive high performance liquid chromatography (HPLC)
      method combined with a novel double cell quartz crystal (DCQC) detector is
      described for the determination of divalent carboxylic acids in traditional
      Chinese herbal and patent medicines. The chromatographic system involves the use
      of a muBondapak-NH2 column with 20 mM KH2PO4 (pH 3.4, adjusted by
      H3PO4)/acetonitrile (95:5%) as a mobile phase. The DCQC detector has a low
      temperature coefficient and high conductance sensitivity independent of the
      background from 7.2 to 2500 microS. Analysis of sample is completed without the
      use of an ion suppression device.

PMID- 10933532
TI  - Characterization of a novel degradation product of 2,2'-dithiobis[N
      isoleucylbenzamide], an inhibitor of HIV nucleocapsid protein zinc fingers.
AB  - Zinc finger motifs have been found to be important in a variety of protein
      structures including transcription factors and viral nucleocapsid proteins.
      Recently, it was demonstrated that various aromatic disulfides effectively remove
      the metal ion from the zinc finger, resulting in an alteration of tertiary
      structure in this region of the protein, thereby inhibiting transcription. Among
      these compounds, 2,2'-dithiobis[N-isoleucylbenzamide] exhibits activity against
      human immunodeficiency virus (HIV)-type 1 in vitro and has been selected for
      preclinical development as an anti-HIV agent. Analysis of this agent by reversed
      phase high-performance liquid chromatography (HPLC) indicated a significant
      quantity of two additional compounds. Identifying the parent disulfide was
      accomplished by scanning eluting peaks with positive ion thermospray ionization
      (TSP) mass spectrometry (MS). Solution-induced disproportionation of the
      disulfide into its sulfhydryl monomer was demonstrated by treating the drug with
      dithiothreitol (DTT) prior to HPLC analysis. TSP-MS analysis of the remaining
      chromatographic peak suggested a molecular weight of 265, which, with 1H-nuclear
      magnetic resonance (NMR) data of the isolated material, allowed us to elucidate
      the chemical structure as N-isoleucyl-benzisothiazolone. Contact with stainless
      steel, such as that employed in an HPLC system, was found to accelerate
      degradation of the parent disulfide to the benzisothiazolone.

PMID- 10933533
TI  - Development and validation of an IL-6 immuno-receptor assay based on surface
      plasmon resonance.
AB  - Interleukin-6 (IL-6) is a pleiotropic cytokine which interacts with the specific
      IL-6 receptor at the surface of the T lymphocytes. A combined immuno- and
      receptor-assay has been developed and validated to characterize the biological
      activity of recombinant IL-6 (rIL-6). This assay is based on Surface Plasmon
      Resonance (SPR) technology. From each experiment two successive interactions were
      monitored: anti-IL-6 antibody/rIL-6 and rIL-6/IL-6 soluble Receptor (sIL-6R).
      Based on the first interaction an immuno-assay for rIL-6 was optimized and
      validated. Based on the second interaction a receptor-assay for rIL-6 biological
      activity was optimized and validated. The assays were validated by performing
      three different assays on three different days. The intra- and inter-day
      precisions (%CV) for the immuno-assay were respectively 0.9% and 1.7%. The
      overall recovery of the immuno-assay was 98.9 +/- 1.6. Intra- and inter-day
      precisions for the receptor-assay were respectively 1.1% and 1.4%. The overall
      recovery of the receptor-assay was 99.4% +/- 1.1. This immuno-receptor assay has
      allowed to compare the rIL-6 stability after storage at different temperatures.
      The results did not show significant difference between the three lower storage
      temperatures (-70, -20 and 5 degrees C). However, results obtained for the
      aliquot stored at 25 degrees C have shown a drastic denaturation of the rIL-6.
      These results illustrate the advantage of this method combining the evaluation of
      the immunological and biological integrity of the drug and high reproducibility
      and precision of the biosensor based technology.

PMID- 10933534
TI  - Photodegradation kinetic study and stability-indicating assay of danazol using
      high-performance liquid chromatography.
AB  - A selective high-performance liquid chromatographic procedure for the stability
      indicating determination of danazol in the presence of its photolytic degradation
      products is demonstrated. The photolysis was carried out in glass vials and
      quartz cell under UV light at 254 nm. Satisfactory results were obtained for the
      assay and recovery testing with RSD values less than 2%. Kinetic parameters
      evaluated comprise the order of reaction and the rate constants of the
      degradation of the danazol irradiated in glass vials or quartz cell.

PMID- 10933535
TI  - Development and validation of an HPLC assay for fentanyl, alfentanil, and
      sufentanil in swab samples.
AB  - A high performance liquid chromatography (HPLC) method for the assay of fentanyl
      citrate, alfentanil hydrochloride, and sufentanil citrate swab samples was
      developed and validated in order to control a cleaning procedure. The swabbing
      procedure involved Super POLX 1200 wipers moistened with water. The assay
      employed extraction of swabs with water and analysis by isocratic, reversed
      phase, HPLC with varying ultraviolet (UV) detection for desired sensitivity,
      depending on the analyte. The method was shown to be selective and linear from
      the limits of quantitation (0.10, 0.20, and 0.15 microg/swab for fentanyl
      citrate, alfentanil, and sufentanil, respectively) to over three times these
      concentrations. The assay limits (detection levels) per swab area were set at
      least at 0.2% of the concentrations of the actives in the drug products (0.02,
      0.10, and 0.10 microg/swab or approximately 0.03, 0.02, and 0.2% for fentanyl
      citrate, alfentanil, and sufentanil, respectively). It should be noted that all
      active concentrations listed in this work were calculated based on the salt form
      concentration for fentanyl (citrate salt) and the free base forms for alfentanil
      and sufentanil. No reference standard was available for alfentanil hydrochloride
      and sufentanil citrate. Drug product was used instead throughout this study.

PMID- 10933536
TI  - Determination of thiols following their separation by CZE with amperometric
      detection at a carbon electrode.
AB  - The amperometric detection (AD) employing a carbon disk electrode as a working
      electrode to determine the thiol compounds, including cysteine (CYS), glutathione
      (GSH), 6-thiopurine (TP), and methimazole (MMI), following their separation by
      capillary zone electrophoresis (CZE) is described in this paper. The detection
      potential was chosen at +1100 mV and all analytes exhibit good response at this
      potential on the carbon disk electrode. The reproducibility, linearity, and
      recovery were evaluated under the optimum conditions. The four analytes can be
      baseline resolved within 20 min and the detection limits reached about 10(-6)
      mol/l of magnitude. The method was applied to the separation and determination of
      the actual thiol samples and the analytical results were satisfactory.

PMID- 10933537
TI  - Optimised extraction of folic acid from multivitamin-mineral preparations for
      liquid chromatographic analysis.
AB  - Degradation of folic acid may occur during extraction of multivitamin-mineral
      preparations. The degradation may be caused by presence of ions such as Fe3+ and
      Cu2+, however, the buffer composition may also be critical. This study presents
      an optimised extraction procedure tested on 24 different products of multivitamin
      mineral tablets. The present method yielded mean recoveries of 97% (n = 20) for
      folic acid and prevented degradation of folic acid in at least 24 h in extracts
      from multivitamin-mineral tablets.

PMID- 10933538
TI  - Simultaneous determination of benzodiazepines in whole blood or serum by HPLC/DAD
      with a semi-micro column.
AB  - A simple and sensitive high performance liquid chromatographic (HPLC) method
      using a semi-micro column, C8 reversed-phase column (3 mm i.d.) and a low flow
      rate 0.3 ml/min was developed and validated for the determination of five
      frequently prescribed benzodiazepines: clonazepam, diazepam, flunitrazepam,
      midazolam and oxazepam. Quantification was performed at 220 nm with
      methylclonazepam as internal standard. The method involved a simple extraction
      from alkalinized blood (1 ml) into 1-chlorobutane and provided excellent
      sensitivity, recovery, accuracy and reproducibility for benzodiazepines in
      therapeutic or toxic concentrations.

PMID- 10933539
TI  - Determination of the pKa values of beta-blockers by automated potentiometric
      titrations.
AB  - The acid-base equilibrium constants of the beta-blockers atenolol, oxprenolol,
      timolol and labetalol were determined by automated potentiometric titrations. The
      pKa values were obtained in water-rich or water methanol medium (20% MeOH) to
      obviate the solubility problems associated with the compounds. The initial
      estimates of pKa values were obtained from Gran's method and then, were refined
      by the NYTIT and ZETA versions of the LETAGROP computer program. The resultant
      values were 9.4 (I = 0.1 M KCl, 20% methanol) for atenolol, 9.6 (I = 0.1 M KCl)
      for oxprenolol, 9.4 (I = 0.1 M KCl, 20% methanol) for timolol and 7.4 and 9.4 (I
      = 0.1 M KCl) for labetalol. The potentiometric method was found to be accurate
      and easily applicable. The operational criteria for applying the methodology are
      indicated.

PMID- 10933540
TI  - High performance liquid chromatographic determination of ambroxol in the presence
      of different preservatives in pharmaceutical formulations.
AB  - A high-performance chromatographic method is described for simultaneous
      determination of ambroxol in the presence of different preservatives in syrups.
      The method separates ambroxol from methyl- ethyl-, propyl- and butyl paraben and
      from other multi-component mixtures. The retention behaviour of ambroxol and
      parabens as a function of both pH and mobile phase composition was investigated.
      The eluents were monitored with a UV detector at 247 nm. Linear relationships
      between the amount of pharmaceutical compounds and peak heights were confirmed at
      the concentrations of 0.74-14.08 microg ml(-1). The high recovery (no extraction
      of the samples is required) and the low %RSD confirm the suitability of the
      proposed method for the determination of ambroxol in different pharmaceutical
      preparations.

PMID- 10933541
TI  - Investigation and analytical application of the reactions of eriochrome cyanine R
      with fluvoxamine and fluoxetine.
AB  - Eriochrome cyanine R (ECR) reacts with fluvoxamine (FXM) and fluoxetine (FXT)
      forming coloured ion-association compounds. The composition of the compounds,
      studied by spectrophometric methods showed that the molar ratio ECR:FXM = 1:2 and
      ECR:FXT = 1:2. The formation and extraction conditions of the compounds were
      established. The compounds were characterised by UV, VIS, and IR spectrometry. It
      was found that the compounds are insoluble in water but quantitatively extracted
      into buthanol. Under the optimal experimental conditions fluvoxamine and
      fluoxetine were determined in the range 2-40 microg/ml and 2-20 microg/ml,
      respectively. The relative standard deviation is about +/- 2%.

PMID- 10933542
TI  - Spectrophotometric determination of two N-(4-quinolyl) anthranilic acid
      derivative (glafenine and floctafenine).
AB  - Spectrophotometric methods were developed for the determination of glafenine and
      floctafenine. The first method depends upon the determination of glafenine in raw
      material and tablets as well as in the presence of its main degradation product
      glafenic acid (up to 40%). Differential first derivative spectral response at 245
      nm in 0.1 N hydrochloric acid, where the corresponding degradation product
      exhibits no contribution in 0.1 N sodium hydroxide. The method allows the
      determination of 2.5-30 microg ml(-1). The second method depends upon the
      reaction of floctafenine with 2,3-dichloro 5,6-dicyano-p-benzoquinone (DDQ) in
      acetonitrile to give highly colored complex that could be measured quantitatively
      at (about) lambda(max) 538 nm. The method permits the determination of 40-180
      microg ml(-1) or by measuring the first derivative spectral response of the color
      at 610 nm. The method permits the determination of floctafenine in presence of
      thiocolchicoside. The methods mentioned both simplicity and sensitivity, having
      excellent precision and accuracy (100.31 +/- 0.63, 100.78 +/- 0.77 and 99.90 +/-
      0.56 for glafenine and floctafenine, respectively). The results were of
      comparable accuracy and reproducibility with the reported methods.

PMID- 10933543
TI  - Poly(vinyl chloride) ion-selective electrodes for piribedil determination.
AB  - Piribedil (PD) ion-selective electrodes have been constructed from poly(vinyl
      chloride) matrix membrane containing piribedil-tetraphenylborate (PD-TPB) as the
      electroactive component with dibutylphthalate or dioctylphthalate as the
      plasticizing solvent mediator. The electrodes displayed a linear response over
      the concentration range 2.0 x 10(-5) to 10(-2) M PD. The working pH ranges of the
      electrodes were 3.5-6.4 and 3.0-6.0, and the isothermal coefficients of the cells
      were 0.00129 and 0.00096 V/degrees C respectively. The electrodes were used for
      the determination of the diprotonated PD species, the most successful being that
      based on dioctylphthalate solvent mediator. The electrodes show a linear response
      over the concentration range of 8.0 x 10(-6) to 10(-2) M PD, with Nernstain slope
      30 mV/PD concentration decade when preconditioned by soaking in distilled water
      for 30 min. The electrodes exhibit good selectivity for the PD with respect to a
      large number of inorganic cations and organic substances of biological fluids.
      Piribedil is determined successfully in pure solutions and in tablets or in
      biological fluids using the standard additions and potentiometric titration
      methods. The membrane withstood soaking in distilled water for more than 5
      months.

PMID- 10933544
TI  - A simple kinetic spectrophotometric method for the determination of oxamniquine
      in formulations and spiked biological fluids.
AB  - A simple and sensitive kinetic method for the determination of oxamniquine in
      pharmaceutical preparations and biological fluids was developed. The procedure is
      based upon a kinetic investigation of the oxidation reaction of the drug with
      alkaline potassium permanganate at room temperature for a fixed time of 20 min.
      The absorbance of the colored manganate ions was measured at 610 nm.
      Alternatively, the decrease in the absorbance of potassium permanganate after
      addition of the drug was measured at 525 nm. The absorbance concentration plots
      in both procedures were rectilinear over the range 0.5-4 microg ml(-1). The
      concentration of oxamniquine is calculated using the corresponding calibration
      equation for the fixed-time method. The determination of oxamniquine by fixed
      concentration and rate-constant methods was feasible with the calibration
      equations obtained but the fixed time method had been found to be more
      applicable. Both procedures were applied to the determination of oxamniquine in
      formulations. The results obtained were in good agreement with those obtained
      using the official method. The fixed time method of 20 min was further applied to
      spiked human urine and plasma, the recoveries (%) were 100.94 +/- 0.57 and 98.07
      +/- 0.88 for urine and plasma, respectively, at 610 nm, and 97.51 +/- 1.27 and
      95.69 +/- 1.23 for urine and plasma, respectively, at 525 nm.

PMID- 10933545
TI  - A chemiluminescent assay for hydroperoxide level of phosphatidylcholine
      hydroperoxide fraction purified by two Sep-Pak cartridges in biological samples.
AB  - A chemiluminescent assay for hydroperoxide level of phosphatidylcholine
      hydroperoxide (PCOOH) fraction purified from biological samples was presented.
      This method utilized of two Sep-Pak cartridges. A lipid soluble fraction was
      isolated from each homogenized tissue or blood by Folch's method. The mixture of
      phosphatidylcholine (PC) and PCOOH was separated from the lipid soluble fraction
      by a Sep-Pak silica cartridge. A Sep-Pak tC18 cartridge made complete separation
      of both PCOOH and PC possible. The hydroperoxide level of PCOOH fraction was
      quantified by the reaction with ferrous ion using 2-methyl-6-[p-methoxyphenyl]
      3,7-dihydroimidazo[1,2-a]pyrazin++ +-3-one as a chemiluminescent dye. The mixture
      of positional isomers, 1-hexadecanoyl-2-[9, or 10-hydroperoxyl octadecanoyl]-sn
      glycero-3-phosphocholine was used as an authentic standard. The good recovery
      rate for authentic PCOOH of 87.1 +/- 11.6% (mean +/- S.E., n = 4) was obtained by
      using two Sep-Pak cartridges. Linear calibration curve was obtained in the range
      from 2.5 to 20 nmol, and the detection limit of the standard was 10 pmol (signal
      to-noise ratio > 3). This method was applied to the investigation of the lipid
      peroxidation induced by reperfusion of the liver with cold preservation,
      mimicking liver transplantation in rats. The effect of liposome-encapsulated
      dichloromethylene diphosphonate (LEDD), which eliminate of Kupffer cells to
      prevent the generation of oxygen radicals on the lipid peroxidation, was compared
      with the untreated group as a control. After 1 h reperfusion at 37 degrees C the
      hydroperoxide level obtained the liver without preservation in the untreated
      group was 12.4 +/- 2.4 nmol/100 mg lipid (n = 4) and levels increased
      significantly by prolongation of the preservation time. On the other hand, the
      hydroperoxide level in the LEDD treated group did not change up to 24 h
      preservation. These results suggest that this improved assay for hydroperoxide
      level of PCOOH fraction in biological samples can be applied to investigations
      involving lipid peroxidation because of its simplicity and accuracy.

PMID- 10933546
TI  - Characterization of clinafloxacin photodegradation products by LC-MS/MS and NMR.
AB  - Exposure of clinafloxacin to light results in photochemical degradation. The
      polar and nonpolar photodegradation products were profiled by HPLC using two sets
      of conditions. Clinafloxacin was subjected to severe light exposure conditions to
      obtain elevated levels of the photodegradation products for characterization. The
      structures of eight new degradation products were elucidated based on information
      from LC-MS/MS fragmentation and NMR spectra following isolation by preparative
      HPLC. Two photodegradation routes were identified: (1) dechlorination, followed
      by further reactions involving the quinolone ring, to yield polar
      photodegradation products; and (2) degradation of the pyrrolidine side-chain,
      yielding the nonpolar photodegradation products.

PMID- 10933547
TI  - In-use testing of extemporaneously prepared suspensions of second generation non
      nucleoside reversed transcriptase inhibitors in support of phase I clinical
      studies.
AB  - DPC 961 and 963 are two of a series of prospective second generation non
      nucleoside reverse transcriptase inhibitors (NNRTIs) being considered for the
      treatment of HIV infections. The 'powder in a bottle' approach was used for drug
      administration for Phase I clinical studies. This new approach consists of
      compounding the active drug as a suspension or solution at the clinical site
      immediately before dosing. Prior to clinical use, studies were conducted to
      determine the compatibility of the drugs with the suspending agent, the recovery
      of the drugs using the administration procedure and the dissolution profile of
      the suspensions. The stability of the DPC 961 and 963 in the dosing formulation
      was followed over a 24-h period using a stability indicating HPLC method. In
      addition, the dissolution profiles of the suspensions were established for future
      comparison with solid dosage forms. Although the two drugs have very similar
      chemical structures, they clearly exhibited different behaviors in liquid/liquid
      extraction and dissolution experiments. These differences could be related to the
      physical characteristics of the powders, such as particle size and surface area.
      The results of the in-use testing of the suspension showed adequate recovery of
      the drugs from the bottle at two drug levels. The stability of DPC 961 and 963 in
      the suspending agent was sufficient for constitution and administration of the
      suspensions at the clinical site.

PMID- 10933549
TI  - Integrated sample collection and handling for drug discovery bioanalysis.
AB  - An integrated sample handling process for drug discovery bioanalysis is
      described. The streamlining of study design, sample collection and automatic
      bioanalytical sample processing is demonstrated. Specific details for the entire
      procedure regarding the time saved, ease of automation and integration are
      defined. Details of sample handling involved a sample collection map, sample
      collection formatting and volume, dilution schemes for high concentration
      samples, choice of biological fluid and evaluating the capabilities of two liquid
      handling workstations. Numerous comparisons were conducted between the new
      approaches and the conventional sample handling approaches. The precision and
      accuracy obtained from the new integrated sample handling process were comparable
      to those obtained from a conventional approach, as were pharmacokinetic profiles
      and parameters. This new sampling process greatly improved the efficiency of drug
      discovery bioanalysis. The integration of pre-clinical protocol design, sample
      collection and bioanalysis processes was also achieved.

PMID- 10933548
TI  - A simple high performance liquid chromatographic method for the quantification of
      total cotinine, total 3'-hydroxycotinine and caffeine in the plasma of smokers.
AB  - A simple isocratic HPLC procedure has been developed for the quantification of
      caffeine and the nicotine metabolites cotinine, 3'-hydroxycotinine, cotinine
      glucuronide and 3'-hydroxycotinine glucuronide in the plasma of smokers. The
      glucuronide conjugates were determined indirectly via initial basic hydrolysis of
      the analyte sample followed by quantification of the resulting deconjugation
      product. Plasma was basified, extracted with dichloromethane, evaporated, the
      residue dissolved water and an aliquot part was analyzed by HPLC. The method
      utilized a Partisil-10 SCX cation-exchange column and an isocratic mobile phase
      of sodium phosphate buffer: methanol (92:8 v/v, 0.1 M, adjusted to pH 4.8 with
      triethylamine) at a flow rate of 1.5 ml/min. UV detection was at 254 nm. All
      solutes were separated with good resolution, and quantification was determined
      using an internal standard of N,N-diethylnicotinamide. The retention times were:
      caffeine 5.1 min, 3'-hydroxycotinine 7.2 min, N,N-diethylnicotinamide 9.5 min,
      and cotinine 15.5 min. Detection limits for caffeine, 3'-hydroxycotinine,
      cotinine, and total cotinine were 10 ng/ml; the detection limit for total 3'
      hydroxycotinine was 20 ng/ml. The inter-day and intra-day variations for all
      analytes were between 1 and 8%. This analytical method is suitable for the
      determination of caffeine and nicotine metabolite levels in large numbers of
      clinical samples.

PMID- 10933550
TI  - Development and validation of a single robust HPLC method for the
      characterization of a pharmaceutical starting material and impurities from three
      suppliers using three separate synthetic routes.
AB  - Novel approaches to the development of analytical procedures for monitoring
      incoming starting material in support of chemical/pharmaceutical processes are
      described. High technology solutions were utilized for timely process development
      and preparation of high quality clinical supplies. A single robust HPLC method
      was developed and characterized for the analysis of the key starting material
      from three suppliers. Each supplier used a different process for the preparation
      of this material and, therefore, each suppliers' material exhibited a unique
      impurity profile. The HPLC method utilized standard techniques acceptable for
      release testing in a QC/manufacturing environment. An automated experimental
      design protocol was used to characterize the robustness of the HPLC method. The
      method was evaluated for linearity, limit of quantitation, solution stability,
      and precision of replicate injections. An LC-MS method that emulated the release
      HPLC method was developed and the identities of impurities were mapped between
      the two methods.

PMID- 10933551
TI  - Determination of free levels of phenytoin in human plasma by liquid
      chromatography/tandem mass spectrometry.
AB  - A liquid chromatography combined with tandem mass spectrometry assay for the
      determination of free levels of the highly protein bound drug phenytoin (5,5
      diphenylhydantoin) in human plasma is described. The assay was demonstrated to be
      reliable, accurate and precise, and specific for phenytoin. The procedure
      involves isolation of the unbound drug from the drug/protein complex by
      ultrafiltration. Liquid-liquid extraction was employed to extract the resultant
      ultrafiltrate. PHT was separated on a 50 x 3 mm reversed-phase column using
      isocratic mobile phase conditions that yielded a run time of 1.5 min, enabling
      high throughput sample analysis. Linearity was obtained over the range 5.00 to
      500 ng/ml. Both between-run and within-run coefficients of variation were less
      than 15% and accuracy's across the assay range were all within 100 +/- 10%. The
      assay was successfully implemented to support a clinical interaction study with
      phenytoin.

PMID- 10933552
TI  - Design of experiment and data analysis by JMP (SAS institute) in analytical
      method validation.
AB  - Validation of an analytical method through a series of experiments demonstrates
      that the method is suitable for its intended purpose. Due to multi-parameters to
      be examined and a large number of experiments involved in validation, it is
      important to design the experiments scientifically so that appropriate validation
      parameters can be examined simultaneously to provide a sound, overall knowledge
      of the capabilities of the analytical method. A statistical method through design
      of experiment (DOE) was applied to the validation of a HPLC analytical method for
      the quantitation of a small molecule in drug product in terms of intermediate
      precision and robustness study. The data were analyzed in JMP (SAS institute)
      software using analyses of variance method. Confidence intervals for outcomes and
      control limits for individual parameters were determined. It was demonstrated
      that the experimental design and statistical analysis used in this study provided
      an efficient and systematic approach to evaluating intermediate precision and
      robustness for a HPLC analytical method for small molecule quantitation.

PMID- 10933553
TI  - Determination of the minor component bromhexine in cotrimoxazole-containing
      tablets by absorption spectrophotometry and partial least-squares (PLS-1)
      multivariate calibration.
AB  - The mucolitic bromhexine [N-(2-amino-3,5-dibromobenzyl)-N-methylcyclohexylamine]
      has been determined in cotrimoxazole-containing tablets by partial least-squares
      (PLS-1) multivariate of spectrophotometric calibration data in the spectral range
      310-350 nm. In the studied commercial tablets, cotrimoxazole is present in large
      excess (ca. 100:1 in weight) with respect to bromhexine, and a high degree of
      spectral overlapping exists among bromhexine and cotrimoxazole components.
      However, the obtained recoveries are reasonably good with the presently discussed
      technique.

PMID- 10933554
TI  - The high performance liquid chromatography electrospray ionization mass
      spectrometry analysis of diverse basic pharmaceuticals on cyanopropyl and
      pentafluorophenylpropyl stationary phases.
AB  - Cyanopropyl (CN) and pentafluorophenylpropyl (PFPP) modified silica columns give
      good retention and good peak shape for the high performance liquid
      chromatography/electrospray ionization/mass spectrometry (HPLC/ESI/MS) analysis
      of several classes of basic drugs. These phases enhance the ESI-MS signal by
      providing good retention of basic drugs with a mobile phase containing 90%
      acetonitrile. With C18 columns, in order to achieve good retention of basic
      drugs, only a mobile phase containing less than 40% acetonitrile can be used.
      Higher concentrations of acetonitrile produce a larger MS signal in the ESI
      process; the MS signal was a factor of 9 and 12 times greater on the CN and PFPP
      phases when compared with the C18 phase for the analysis of codeine. The C18
      phase required only 4.0-6.0% acetonitrile to obtain the same retention time for
      codeine. The CN and PFPP stationary phases can be used for the analysis of a
      range of basic drugs, including many compounds which are poorly retained on the
      popular C18 and C8 stationary phases. Applications of CN and PFPP columns in the
      HPLC/ESI/MS of basic drugs include the analysis of antimalarials, such as
      quinine, bronchodilators, such as salbutamol and tulobuterol, cardioactive drugs,
      such as procainamide and beta-blockers, tricyclic antidepressants (TCAs), such as
      protriptyline and trimipramine and alkaloids, such as morphine and codeine. The
      CN and PFPP phases are also useful for the analysis of bufuralol and its
      metabolite, hydroxy-bufuralol. All the above analyses were performed using the
      same mobile phase, 90% acetonitrile; thus the HPLC method development process was
      expedited. The CN and PFPP phases also gave reproducible retention times and peak
      shape after more than 8 h of analyses.

PMID- 10933555
TI  - Simultaneous determination of a novel thrombin inhibitor and its two metabolites
      in human plasma by liquid chromatography/tandem mass spectrometry.
AB  - I, 3-(2-phenethylamino)-6-methyl-1-(2-amino-6-methyl-5-methylene-c
      arboxamidomethylpyridinyl)-pyrazinone dihydrochloride monohydrate, is a potent,
      orally active thrombin inhibitor. The compound also has two metabolites which
      have been shown to have thrombin inhibitory activity: benzylic alcohol M3
      metabolite (II) and hydroxymethylpyrazinone M7 metabolite (III). A liquid
      chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous
      determination of I and its two metabolites in human plasma has successfully been
      developed. The method consists of treating 0.5 ml plasma with 2 N NaOH and
      extracting I, II, III and internal standard (IV) with ethyl acetate:methyl-t
      butyl ether (1:3, v/v). The analytes were then back-extracted into 2% formic
      acid. The analytes were chromatographed by high performance liquid chromatography
      (HPLC) and detected by MS/MS. Positive ionization was used on a heated nebulizer
      probe monitoring precursor --> product ion combinations in multiple reaction
      monitoring mode. The linear range is 0.5-1000 nM for I and III and 0.75-1000 nM
      for II. Recoveries were 88, 74, 78 and 102.1% for I, II and III and the internal
      standard, respectively in human plasma. Intraday variation using this method was
      < or = 7.9% for I, < or = 9.0%, for II and < or = 9.5% for III across the
      standard curve range. This method exhibits good linearity and reproducibility for
      the three analytes.

PMID- 10933556
TI  - Age of restorations at replacement in permanent teeth in general dental practice.
AB  - The ages of 6,761 restorations replaced in permanent teeth, 6,088 in adults > or
      =19 years of age and 673 in adolescents < or =18 years, were available for
      analyses. The results showed that the median age of amalgam restorations in
      adults was 11 years and that of resin-based composite restorations 8 years. This
      difference in longevity was significant (P = 0.000 l). The median age of failed
      conventional glass ionomer restorations in adults was 4 years and for resin
      modified glass ionomer 2 years. In adolescents, the median longevity of failed
      amalgam restorations was 5 years and that of composite restorations 3 years,
      while both types of glass ionomers had a median longevity of 2 years. The data
      were subdivided based on clinician gender and practice setting. The results
      showed that the median age of amalgam and composite restorations replaced Its
      male clinicians was higher than that for female clinicians irrespective of
      clinical setting. The median age of amalgam and composite restorations replaced
      by salaried dentists was significantly lower than that by private practitioners.
      Minor differences were noted in longevity of restorations between male and female
      patients. The age of replaced restorations was shortest for the group of
      clinicians with the least clinical experience and highest for those that
      graduated > or = 30 years ago.

PMID- 10933557
TI  - Attitudes to dental health and care among 20 to 25-year-old Swedes: results from
      a questionnaire.
AB  - During the last 3 decades, large resources have been allocated through the
      organized dental care system for the improvement of dental health among children
      and teenagers in Sweden. The aim of this study was to describe attitudes related
      to dental health and dental care among 20 to 25-year-old Swedes. A random sample
      of 650 individuals was drawn from the database of the National Social Insurance
      Board of Sweden. A postal questionnaire comprising 70 questions was delivered to
      the subjects and the response rate was 78%. A high proportion of the respondents
      considered themselves to have a high need for dental care. They had a strong
      conception of being able to influence their own dental health. Quite a few were
      concerned about their dental health. A high proportion indicated that they were
      satisfied with their dental function, but fewer individuals were satisfied with
      the appearance of their teeth. The respondents also reported good reception by
      their dentists, although opinions differed between the sexes. Women reported a
      significantly higher degree of discomfort and unease than men. Most respondents
      had adopted good oral hygiene habits but dental floss was rarely used. The
      majority of subjects indicated that they attended dental examinations on an
      annual basis. There is a need for further investigation into patients' attitudes
      to dental health and dental care. It is important to understand the significance
      patients attach to different concepts in the dental treatment. This would enhance
      our understanding of how the concept of felt need is expressed and transformed
      into demand for care.

PMID- 10933558
TI  - Neuroendocrine cells in Malassez epithelium and gingiva of the cat.
AB  - Malassez epithelium has been designated as epithelial cell rests, the biological
      significance of which is still under debate. This study was designed to analyze
      Malassez epithelium for the presence of neuroendocrine cells. Gingival tissue was
      included as a positive control. Using immunohistochemistry, confocal and light
      microscopy, Malassez epithelium and gingival epithelium from mature cats (n = 5)
      were examined for cells containing the neuropeptides calcitonin gene-related
      peptide (CGRP), substance P (SP), and vasoactive intestinal peptide (VIP). Both
      Malassez epithelium and the basal epithelial cell layers in gingival rete pegs
      regularly displayed cells immunoreactive to CGRP, SP, and VIP. The immunopositive
      cells were most frequently present in the epithelial cell clusters and strands of
      Malassez located in the cervical half of thc periodontal ligament. Double
      immunolabeling revealed cellular co-expression of CGRP or SP with VIP, and the
      neuropeptides were co-localized in the cellular compartments. Labeled cells in
      both epithelia were occasionally supported by immunoreactive nerve fibers. This
      study shows that cells immunoreactive to CGRP, SP, and VIP arc located within the
      cat Malassez epithelium. The localization of neuroendocrine cells verifies the
      diversity of this epithelium and confirms that Malassez epithelium is composed of
      different cell types, in common with epithelia from other locations. The presence
      of neuroendocrine cells in Malassez epithelium strongly suggests biological
      functions of this tissue, and the neuropeptide content may thus indicate
      endocrine functions of the cells.

PMID- 10933559
TI  - Dental conditions in middle-aged and older people in Denmark and Sweden: a
      comparative study of the influence of socioeconomic and attitudinal factors.
AB  - In 1998-99 two parallel questionnaire studies were performed in Denmark and
      Sweden. In Denmark the age group was 45-69 years and in Sweden 55-79 years. One
      aim was to study the influence of socioeconomic and attitudinal factors on dental
      status in the two countries. For the comparable age groups 55-69 years there was
      a striking difference in dental conditions between the countries. In Sweden, 72%
      had either all teeth remaining, missing teeth replaced by fixed prosthodontics,
      or only one or two single missing teeth not replaced. The corresponding figure
      for Denmark was 44%. Among Danes, 34% were wearing removable denture(s) or were
      edentulous in one jaw or both jaws, compared with 15%, among Swedes. In logistic
      regression models, higher income and longer education were significantly
      associated with the best dental status categories in Denmark but not in Sweden.
      In the model with wearing removable denture(s) as the dependent variable, lower
      income and lower education level showed a significant influence for the Danes. In
      Sweden, lower income showed a significant influence but education level was
      insignificant. In both Denmark and Sweden, a positive attitude toward the
      importance of dental appearance was associated with an increased risk of wearing
      removable denture(s).

PMID- 10933560
TI  - Longitudinal radiological study of the oral health parameters in an elderly
      Finnish population.
AB  - In the oldest elderly, an increase in the number of remaining teeth may increase
      oral infection foci. The aim of this follow-up study was to examine the
      radiologically detected oral health condition of a group of home-living elderly
      in Helsinki at 5-year intervals. The population of this study comprised 103 home
      living elderly people, all participants of the population-based Helsinki Aging
      Study. Panoramic radiography supplemented by intraoral radiographs was performed
      on all these participants at the Institute of Dentistry, University of Helsinki,
      in 1990-1991. Follow-up radiographic examination was completed in 1995-1996. Mean
      number of teeth decreased during the follow-up period from 13.2 +/- 9.0 to 12.5
      +/- 9.2 (P= 0.0001). Mean number of teeth with periapical lesions decreased in
      men from 1.3 +/- 1.4 to 0.6 +/- 0.9 (P = 0.007), but no differences in number of
      teeth with periapical findings were observed in women. There were relatively few
      changes in the subjects' radiographic periodontal findings. However, fewer teeth
      with vertical bone pockets >1-3 mm deep were found in the follow-up study than 5
      years earlier (0.6 +/- 1.2 vs 1.1 +/- 1.8; P= 0.0008). In both the baseline and
      the follow-up studies the radiographic findings occurred in the subjects who had
      retained more natural teeth. In the follow-up study, 68% of the subjects had
      radiographically detected signs of chronic oral infection foci. It may be
      concluded that radiographically detected oral health parameters remain relatively
      unchanged, but treatment need is higher among those who have successfully
      retained their natural dentition into old age.

PMID- 10933561
TI  - Perioral and dental perception of mechanical stimulus among subjects with and
      without awareness of bruxism.
AB  - We studied whether perioral and dental sensitivity to mechanical stimulation is
      changed in subjects with awareness of bruxism. Tactile detection threshold in the
      vermilion border of the lower lip and in the upper incisor was determined using
      calibrated monofilaments (von Frey hairs) and spatial resolution threshold of the
      lip was determined using a grating orientation task. The tactile detection
      threshold and the spatial resolution threshold in the perioral region were not
      significantly different between bruxers (n = 7) and asymptomatic control subjects
      (n = 13). Neither was the detection threshold for mechanical stimulation of the
      tooth different between bruxers (n = 6) and asymptomatic controls (n = 6). It is
      concluded that the tactile sensitivity of perioral region or the tooth is not
      significantly changed in subjects with awareness of bruxism.

PMID- 10933562
TI  - Changes in masticatory mandibular movements in growing individuals: a six-year
      follow-up.
AB  - The pattern of mandibular movement during chewing is influenced by several
      central and peripheral factors. The aim of the present study was to determine
      whether changes in masticatory function, characterized by mandibular velocity and
      displacement, occurred during individuals' normal growth. Forty-seven children, 9
      15 years of age, were followed over a 6-year period. All had an Angle Class I
      occlusion with no obvious orthodontic problems. Oral motor function with respect
      to mandibular displacement, duration, and velocity was monitored 3-dimensionally
      with an opto-electronic method. The chewing cycle was divided into an opening,
      closing, and occlusal phase. Total body height was measured. During the follow-up
      period, all masticatory variables except the 3-dimensional opening distance
      showed significant changes. The total chewing cycle duration, the opening and
      occlusal time of the chewing cycle, and the 3-dimensional closing distance
      increased during the growth period, while the closing time of the chewing cycle,
      the 2-dimensional lateral and vertical distances and both the opening and closing
      velocity decreased. The children who grew proportionally most in height during
      the 6-year period, i.e. the youngest children in the group studied, showed a
      significantly larger decrease in the opening velocity. From this study it becomes
      evident that the variables of the chewing cycle undergo a continuous process of
      change during growth. This is possibly a reflection of anatomical changes,
      maturation of the central nervous system, and altered functional demands.

PMID- 10933563
TI  - Swedish dentists' decisions on preparation techniques and restorative materials.
AB  - This study aimed at mapping the preparation techniques and restorative materials
      that Swedish dentists are using for primary approximal and occlusal carious
      lesions. It involved sending a pre-coded questionnaire to a random sample of 923
      dentists, with eight items concerning approximal and occlusal restorative
      preparation techniques and dental materials. Responses were received from 651
      (70.5%) dentists. To restore a primary approximal carious lesion in an adolescent
      with low caries activity and good oral hygiene, the tunnel preparation was chosen
      by 48% of the dentists, the saucer-shaped preparation by 32%, and the traditional
      Class II preparation by 20%. The most common preparation technique for restoring
      an occlusal carious lesion was removal of the carious part only, which was chosen
      by 74% of the dentists. For a lower second molar with a minor occlusal caries
      lesion combined with a suspected dentin lesion as judged radiographically, about
      half of the dentists chose to restore the carious part only and 27% would seal
      the rest of the fissure system in addition. For a similar lesion with no obvious
      radiolucency in the dentin, about 1/3 chose the 'no treatment' alternative, 1/3
      fluoride treatment, and the rest fissure sealing or other techniques. Composite
      was used most often and amalgam least often for both approximal and occlusal
      carious lesions.

PMID- 10933564
TI  - An insulin receptor gene polymorphism is associated with diastolic blood pressure
      in Chinese subjects with components of the metabolic syndrome.
AB  - Insulin resistance has been described as a possible underlying link for the
      clustering of Type 2 diabetes mellitus, hypertension, obesity, and dyslipidemia,
      known as the metabolic syndrome. Mutations within the insulin receptor have been
      associated with hypertension in some white and Oriental populations. We examined
      the relationship between the insulin receptor NsiI restriction fragment-length
      polymorphism (RFLP) and biochemical and anthropometric parameters associated with
      these disorders in 933 Chinese subjects. Of the 933 subjects, 117 were control
      subjects and 816 had one or more components of the metabolic syndrome: 59.7%
      hypertension, 64.6% glucose intolerance, 55.3% dyslipidemia, and 53.3% obesity.
      The prevalences of the N1 allele and N1N1 genotype were 74.4% and 55.8%,
      respectively, in the whole population. No differences were observed in the
      genotype and allele frequency distributions between the control group and the
      cohorts with glucose intolerance, hypertension, or dyslipidemia alone or in
      combination. Using one-way ANOVA, there was a weak relationship between the
      insulin receptor genotypes and diastolic blood pressure (DBP), P = .069. The DBP
      was significantly higher in subjects carrying the N1N1 genotype in both the total
      population (80 +/- 13 v 76 +/- 12 mm Hg, P = .038) and subjects with glucose
      intolerance (80 +/- 12 v 76 +/- 10 mm Hg, P = .048). Using stepwise multiple
      regression, the insulin receptor NsiI polymorphism was found to be an independent
      predictor of DBP in this Chinese population, P = .018. Age, gender, and body mass
      index (BMI) were also included in the analysis and were all significantly
      associated with diastolic DBP. To conclude, the insulin receptor gene NsiI RFLP
      is associated with DBP in these Chinese subjects.

PMID- 10933565
TI  - Association of plasma viscosity and carotid thickening in a French working
      cohort.
AB  - Plasma viscosity and intima-media thickness (IMT) are frequently associated with
      cardiovascular disease and its risk factors. We evaluated the association of
      rheologic and vascular factors in asymptomatic subjects. Plasma viscosity
      (coaxial cylinder viscometry) and both preintrusive and intrusive atherosclerosis
      in the carotid arteries (ultrasonography) were investigated in 246 men and 337
      women aged 17 to 65 years from the AXA study, a prospective cohort of healthy
      workers. Plasma viscosity was positively related to age-adjusted mean bifurcation
      carotid artery IMT (P < .01 for men; P < .04 for women) and maximum carotid
      artery IMT (P < .01 for men; P < .02 for women), but not to mean common carotid
      artery IMT. Multivariate adjustment affected these relations to a greater extent
      in men than in women. The odds ratio (range) of having intrusive atherosclerosis
      in relation to 1 SD greater plasma viscosity was 2.27 (1.52 -3.38) in men and
      1.63 (1.17-2.26) in women. Adjustment of age, waist-to-hip ratio, smoking,
      hypercholesterolemia, hypertension, diabetes, and fibrinogen had very little
      effect on the magnitude of these odds ratios. Thus, plasma viscosity was
      associated with carotid thickening, suggesting that rheologic factors are
      involved in the subclinical phase of atherosclerosis.

PMID- 10933566
TI  - Studies on flow-mediated vasodilation and intima-media thickness of the brachial
      artery in patients with primary hyperparathyroidism.
AB  - The endothelium is a newly recognized target organ of parathyroid hormone (PTH)
      and may contribute to its effects on vascular tone and blood pressure regulation.
      Flow-mediated vasodilation (FMD), brachial and carotid intima-media thickness
      (IMT) were studied in patients with primary hyperparathyroidism (pHPT) and
      controls to evaluate endothelial function and structural arterial vessel wall
      alterations. Sixteen patients with pHPT (mean +/- SEM, age 44 +/- 5 years; PTH
      229 +/- 72 ng/L; serum calcium 3.0 +/- 0.06 mmol/L; serum phosphate 2.0 +/- 0.2
      mg/L) and 16 normocalcemic control subjects matched for age, sex, and blood
      pressure were included. Diabetes, hypertension, and vascular disease were
      excluded in both groups. End-diastolic diameter, flow-mediated (FMD) and
      nitroglycerin-mediated (NMD) dilation of the brachial artery were measured by a
      multigate pulsed Doppler system (echo-tracking). IMT was determined using
      automatic analysis of the M-line signal. Endothelium-dependent FMD was impaired
      in patients compared to controls (4.6 +/- 1.6% v 19.2 +/- 3.9%, P < .001). NMD
      (23.8 +/- 3.1% v. 22.4 +/- 2.8%, P = NS), carotid and brachial IMT (0.60 +/- 0.04
      mm v 0.64 +/- 0.06 mm, P = NS, and 0.46 +/- 0.04 mm v 0.47 +/- 0.08 mm, P = NS,
      respectively) and artery diameters were not different. Endothelium-dependent
      vasodilation is impaired in patients with primary hyperparathyroidism despite
      normal IMT. Endothelial dysfunction may contribute to increased cardiovascular
      morbidity and mortality in pHPT.

PMID- 10933567
TI  - Membrane, intracellular, and plasma magnesium and calcium concentrations in
      preeclampsia.
AB  - Changes in intracellular calcium and magnesium concentrations seem to be involved
      in the pathogenesis of preeclampsia, whereas the role of cell membranes has not
      been studied in detail yet. To investigate the changes in calcium and magnesium
      metabolism in normal pregnancy and preeclampsia, plasma, intracellular, and
      membrane calcium and magnesium concentrations were determined in a clinical
      study. Twenty-five control, 18 untreated healthy pregnant, and 16 nulliparas
      preeclamptic women were investigated. Plasma, cellular, and membrane
      (erythrocytes) calcium and magnesium contents were measured by atomic absorption
      spectroscopy. Plasma and intracellular magnesium concentrations were
      significantly lower in the healthy pregnant group and the preeclamptic group as
      compared to controls (P < .01). In erythrocyte membranes magnesium content was
      found significantly decreased in the preeclamptic women as compared to healthy
      subjects (P < .001). There was a significant decrease in the plasma calcium
      concentration in the preeclamptic group compared to controls or healthy pregnant
      women (P < .05). Membranous calcium content was significantly increased in the
      preeclamptic group versus controls or healthy pregnant women (P < .001) and an
      inverse correlation with membranous magnesium content was found (r = -0.79,P <
      .01). Lowered plasma, intracellular, and membrane magnesium concentrations in
      preeclampsia may contribute to the development in hypertension in pregnancy. In
      addition, a disturbed calcium homeostasis is observed in preeclampsia.

PMID- 10933568
TI  - Temporal relation between blood pressure and serum creatinine in young adults
      from a biracial community: the Bogalusa Heart Study.
AB  - It is well recognized that end-stage renal disease (ESRD) is associated with
      accelerated and malignant hypertension. The association of renal disease and what
      is considered as normal blood pressure is still not clear. The present study
      examined the temporal relation between blood pressure and renal function
      reflected by serum creatinine in a biracial (black-white) community-based
      population enrolled in the Bogalusa Heart Study. The study included 662 young
      adults aged 19 to 32 years, (white men, n = 188; white women, n = 289; black men,
      n = 67; and black women, n = 118) who were followed for an average of 7.4 years.
      In black men, partial correlation adjusted for age, body mass index, serum
      glucose, uric acid, and cigarette smoking showed that baseline systolic and
      diastolic blood pressure are not significantly related to baseline serum
      creatinine, but significantly related to serum creatinine at follow-up (r = 0.38,
      P = .008 and r = 0.42, P = .003, respectively). Multivariate regression analysis
      further showed a significant prediction of serum creatinine at follow-up by
      baseline systolic and diastolic blood pressure (0.031 mg/dL and 0.037 mg/dL rise
      in follow-up serum creatinine for every 10 mm Hg increase in systolic (P = .000)
      and diastolic (P = .001) blood pressure at baseline, but not the other way
      around. Other race and sex groups did not show such significant temporal
      relations. We conclude that in young black men, higher blood pressure levels
      within normal range precede and explain part of the increase in serum creatinine,
      a measure of decline in renal function. Thus, our results underscore the
      beneficial effect of maintaining blood pressure levels lower than what is
      considered as the upper normal limit, particularly in black men.

PMID- 10933569
TI  - Intermediate but not low doses of aspirin can suppress angiotensin-converting
      enzyme inhibitor-induced cough.
AB  - This self-matched control study aimed to compare the efficiency of two different
      regimens of active treatment: aspirin in low (100 mg daily) versus intermediate
      (500 mg daily) doses in abolishing angiotensin-converting enzyme inhibitor (ACEI)
      induced cough. A dry bothersome cough is the most common adverse class effect of
      all angiotensin-converting enzyme inhibitors. Prostaglandins (PG) have been
      pinpointed as playing a leading role in the genesis of ACEI-associated cough. The
      role of different doses of the most commonly used PG inhibitor-aspirin-in ACEI
      cough modification was not yet elucidated. Of 350 consecutive ACEI-treated
      patients, we identified 34 (9.7%) nonsmoking ACEI-related coughers. Patients with
      lung disease, nonsteroidal anti-inflammatory drug (NSAID) treatment, and those
      who did not agree to participate in the study were excluded. In the remaining 14
      ACEI coughers (eight men, six women; mean age, 63 +/- 11 years), the treatment
      was discontinued; the dry cough completely disappeared, but returned in all
      patients within 1 week after ACEI reintroduction. At the end of the rechallenge
      period, patients started a low dose of aspirin for 1 week, switching thereafter
      to the intermediate dose of aspirin for an additional week. On each visit the
      cough severity (CS, 0-4) and frequency (CF, 0-10) scores were registered. Low
      doses of aspirin were ineffective in suppressing ACEI-induced cough, whereas
      intermediate doses completely abolished cough in five patients and reduced
      coughing in all but one patient; CS and CF decreased, respectively, from 2.5 +/-
      1.0 to 0.9 +/- 1.1, P < .002 and from 6.6 +/- 2.4 to 2.4 +/- 1.1, P < .0002.
      Overall, intermediate doses of aspirin beneficially modified cough scores in 13
      (93%) patients, enabling nine (64%) to continue ACEI treatment. Aspirin did not
      influence blood pressure control either in hypertensives or in postinfarction
      patients. We conclude that intermediate but not low doses of aspirin probably can
      suppress ACEI-induced cough. These findings propose a new alternative therapeutic
      approach for patients with ACEI-related cough, especially those in whom ACEI
      treatment seems to be essential.

PMID- 10933570
TI  - Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment
      with irbesartan or atenolol.
AB  - Essential hypertension is often accompanied by abnormalities of the
      coagulation/fibrinolytic system, predisposing to a procoagulant state. The aim of
      the present study was to compare the effects of atenolol (beta1-blocker agent)
      and irbesartan (angiotensin II type 1 receptor antagonist) on plasma levels of
      hemostatic/fibrinolytic and endothelial function markers in a cohort of
      previously untreated hypertensives. Fifty-four patients were randomly assigned to
      atenolol 25 to 150 mg (26 patients) or irbesartan 75 to 300 mg (28 patients). The
      plasma levels of plasminogen activator inhibitor-1 antigen, thrombomodulin,
      tissue factor pathway inhibitor antigen, fibrinogen, and factor XII were
      determined before and after 6 months of therapy. Age, gender distribution, body
      mass index, lipid profile, and baseline values of the measured markers were
      similar in both groups. Baseline values for systolic and diastolic blood
      pressure, as well as the reduction after treatment, were not significantly
      different between the two groups. Treatment with irbesartan was associated with a
      significant decrease in the levels of all the parameters. Similar findings were
      observed in the atenolol group, except for factor XII and tissue factor pathway
      inhibitor levels, which were not significantly decreased in this group. The
      reduction, however, of fibrinogen, plasminogen activator inhibitor-1, and
      thrombomodulin was significantly greater in the irbesartan than in the atenolol
      group. In conclusion, the results indicated that, despite an equally controlled
      blood pressure, 6-month therapy with irbesartan was associated with a more
      favorable modification of hemostatic/fibrinolytic status than atenolol.

PMID- 10933572
TI  - Exercise echocardiography versus exercise electrocardiography in the diagnosis of
      coronary artery disease in hypertension.
AB  - In hypertension, coronary artery disease (CAD) can be overestimated by stress
      electrocardiography (ECG) and scintigraphy due to frequent false-positive
      results. Exercise tests are also limited by an excessive blood pressure increase,
      and pharmacologic pressure normalization decreases the accuracy of the test. The
      aim of this study was to assess the accuracy of exercise echocardiography as an
      alternative test for CAD detection in hypertension, both before and after
      adequate blood pressure control. We studied 59 hypertensive and 59 normotensive
      patients undergoing coronary angiography for chest pain. Upright bicycle exercise
      ECG and echocardiographic tests were performed in each group in the absence of
      therapy; in hypertensives, the tests were repeated a day apart after blood
      pressure normalization with sublingual nifedipine. Significant CAD (lumen
      narrowing >50%) was detected in 22 hypertensive and 41 normotensive patients. In
      the two groups, sensitivity, specificity, and diagnostic accuracy of exercise
      echocardiography performed before treatment were not statistically different
      (95%, 94%, 94% in hypertensives and 82%, 77%, 83% in normotensives,
      respectively), but were significantly higher than for the exercise ECG test (68%,
      70%, and 69%, respectively). After blood pressure lowering, exercise
      echocardiography sensitivity slightly decreased (91%), whereas specificity (100%)
      and diagnostic accuracy (96%) did not vary; on the contrary, exercise ECG
      sensitivity decreased to 45%. Therefore, according to our data, exercise
      echocardiography can be an accurate test and more reliable than exercise ECG to
      detect CAD in normotensives as well as in hypertensives. Normalization of blood
      pressure with nifedipine does not affect its accuracy, but markedly reduces the
      sensitivity of exercise ECG.

PMID- 10933571
TI  - The influence of left ventricular geometry on coronary vasomotion in patients
      with essential hypertension.
AB  - The objective of this study was to assess the influence of left ventricular (LV)
      geometric pattern on coronary vasomotion in patients with essential hypertension.
      We studied 34 hypertensive patients, who had never been treated, with
      angiographically normal coronary arteries. Patients were classified into four LV
      geometric patterns by echocardiography: normal, concentric remodeling, eccentric
      hypertrophy, and concentric hypertrophy. The responses of coronary vasomotion in
      left anterior descending artery to vasoactive agents (acetylcholine, isosorbide
      dinitrate, adenosine triphosphate) were examined using a Doppler guidewire and
      quantitative coronary angiography. The percent increase in coronary blood flow
      evoked with acetylcholine (endothelium-dependent vasomotion) showed lowest in
      concentric hypertrophy, followed by eccentric hypertrophy, concentric remodeling,
      and normal geometry. The significant linear relationship between acetylcholine
      induced coronary blood flow and LV mass was noted. There was no difference in the
      percent increase in coronary blood flow evoked with isosorbide dinitrate
      (endothelium-independent vasomotion of conduit vessel) among the four groups. The
      percent increase in coronary blood flow evoked with adenosine triphosphate
      (endothelium-independent vasomotion of resistant vessel) was significantly lower
      in patients with concentric hypertrophy than in the other three groups. The
      results in this study suggest that coronary vasomotion may be associated with LV
      geometry in patients with hypertension. The endothelium-dependent vasodilation is
      impaired progressively as LV hypertrophy advances. The endothelium-independent
      vasodilation of microvessels is impaired only in concentric hypertrophy. This
      advanced abnormality of coronary vasomotion may contribute to the high
      cardiovascular morbidity and mortality in patients with concentric hypertrophy.

PMID- 10933573
TI  - Different structural vascular changes in angiotensin II-treated and cold-stressed
      rats.
AB  - The role of the renin-angiotensin and sympathetic nervous system in the
      pathogenesis of structural vascular changes in experimental hypertension was
      investigated by comparing the effect of angiotensin II (ANG II) administration
      and of sympathetic stimulation by cold stress on the structure and composition of
      mesenteric arteries of rats. Adult male Sprague-Dawley rats were administered
      subcutaneously 100 ng/kg per min ANG II or exposed to 5 degrees C cold overnight
      for 12 weeks. Sham-operated rats were controls. At the end of treatment, the
      mesenteric circulation of rats was perfusion-fixed for morphometric measurements
      by light microscopy and volume density measurements by point counting on electron
      micrographs. Tail systolic blood pressure of ANG II-treated rats increased by 37
      mm Hg at week 2 and remained elevated for the rest of the experiment. The
      systolic BP of cold-stressed rats measured at room temperature did not change.
      These findings were confirmed by direct measurement of mean arterial pressure in
      free-moving rats. Compared to control rats, medial thickening of large and small
      arteries in ANG II-treated and cold-stressed rats was the main finding of this
      study. Thickening of the media in the two treated groups of rats appeared to be
      due to hypertrophy of vascular muscle, as indicated by the increased width of
      smooth muscle cells. Loose matrix (interstitial fluid compartment) was increased
      in media of large arteries of ANG II-treated rats, and collagen was increased in
      the outer media of arteries of cold-stressed rats. Measurements of compositional
      changes in addition to morphometric changes are needed to detect differences in
      the pathogenesis of structural vascular changes in the various forms of
      hypertension.

PMID- 10933574
TI  - Afferent arteriolar reactivity to angiotensin II is enhanced during the early
      phase of angiotensin II hypertension.
AB  - Increased renal microvascular reactivity may contribute to the blunted pressure
      natriuretic response and increase in blood pressure during the development of
      angiotensin II hypertension. The current studies were performed to determine
      renal microvascular reactivity during the early phases of angiotensin II-infused
      hypertension. Male-Sprague Dawley rats received angiotensin II (60 ng/min) or
      vehicle via an osmotic minipump. Normotensive and angiotensin II hypertensive
      rats were studied 1 and 2 weeks after implantation of the minipump. Systolic
      blood pressure averaged 117 +/- 4 mm Hg (n = 31) before pump implantation.
      Angiotensin II infusion increased systolic blood pressure to 149 +/- 3 and 187 +/
      5 mm Hg on infusion days 6 and 12, respectively. Renal microvascular responses
      to angiotensin II and norepinephrine at renal perfusion pressures of 100 and 150
      mm Hg were observed using the in vitro juxtamedullary nephron preparation.
      Afferent arteriolar diameters of 1-week normotensive animals averaged 22 +/- 1
      microm and after 2 weeks of vehicle infusion averaged 21 +/- 1 microm at a
      perfusion pressure of 100 mm Hg. In animals infused with angiotensin II for 1 or
      2 weeks, diameters of the afferent arterioles perfused at a pressure of 100 mm Hg
      were 20% and 9% smaller, respectively. Additionally, 1- and 2-week hypertensive
      animals had an enhanced responsiveness of the renal microvasculature to
      angiotensin II. At a perfusion pressure of 100 mm Hg, angiotensin II (10 nmol/L)
      decreased afferent arteriolar diameter by 26 +/- 5% and 22 +/- 3% in the 1- and 2
      week angiotensin II hypertensive rats, respectively. In 1- and 2-week
      normotensive animals, angiotensin II (10 nmol/L) decreased afferent arteriolar
      diameter by 18 +/- 2% and 15 +/- 2%, respectively, at a perfusion pressure of 100
      mm Hg. In contrast, the afferent arteriolar response to norepinephrine was not
      altered in angiotensin II hypertensive rats. These data demonstrate an elevated
      renal microvascular resistance and enhanced vascular reactivity that is selective
      for angiotensin II in the early phases of hypertension development after infusion
      of angiotensin II. Thus, an alteration in renal microvascular function
      contributes to the blunted pressure natriuretic response and progressive
      development of hypertension.

PMID- 10933575
TI  - Microvascular responses to endothelin in deoxycorticosterone acetate-salt
      hypertensive rats.
AB  - The objective of the present study was to determine if endothelin-1 played a role
      in the elevated peripheral resistance in deoxycorticosterone-acetate (DOCA)-salt
      hypertension. Radioimmunoassay showed that the concentration of endothelin-1 was
      higher in thoracic aorta of the DOCA-salt group than that of the control
      normotensive (CN) group. Responses of arterioles in the rat cremaster to
      endothelin-1 were also observed using in vivo closed circuit television
      microscopy. Microvascular sensitivity to endothelin-1 was decreased in the DOCA
      salt group. In the presence of an endothelin type A (ET-A) receptor antagonist,
      low concentrations of endothelin-1 induced a significant vasoconstriction in the
      DOCA-salt group. In the presence of endothelin type B (ET-B) receptor antagonist,
      microvascular responses to endothelin-1 were attenuated in the DOCA-salt group.
      These results indicated that the increased tissue level of endothelin-1 may
      decrease the ET-A receptor-mediated vascular response to endothelin-1. However,
      the ET-B receptor-mediated vasoconstriction is potentiated during DOCA-salt
      hypertension.

PMID- 10933577
TI  - Glomerular basement membrane polyanion distribution and nitric oxide in
      spontaneous hypertensive rats: effects of salt loading and antihypertensive
      therapy with propranolol.
AB  - Cationic colloidal gold (CCG), a polycationic histochemical probe, was used to
      analyze the distribution of glomerular basement membrane (GBM) polyanions, mainly
      heparan sulfate proteoglycan in spontaneous hypertensive rats (SHR) with or
      without salt loading and antihypertensive treatment with propranolol. The changes
      of mean GBM width and anionic sites distribution were assessed by electron
      microscopy. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO2) +
      nitrate (NO3), stable metabolites of NO. SHR had decreased NO production and
      increased GBM width (27%) compared with the control Wistar-Kyoto (WKY) rats. The
      chronic high dietary salt intake resulted in a significant increase in blood
      pressure, proteinuria, and renal function in the SHR rats. The chronic high salt
      dietary intake resulted in a decrease in NO in the WKY and a further reduction in
      NO production in the SHR. The GBM anionic sites count was similar in the SHR and
      WKY nonsalt-loaded groups, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/microm GBM,
      respectively, but significantly lower in both salt-loaded SHR and WKY, 9.9 +/-
      0.55 (P < .01) and 9.6 +/- 0.55 (P < .01) CCG counts/microm GBM, respectively.
      Antihypertensive treatment with propranolol in the salt-loaded SHR group resulted
      in lower blood pressure, a further decrease in NO production, but no significant
      changes in GBM width and anionic sites count. It is concluded that chronic high
      salt intake may be deleterious to the permselectivity of the GBM. A low NO
      production state that results from chronic salt loading in already hypertensive
      rats will result in more severe organ (renal) damage, most probably by the
      addition of the loss of GBM permselectivity to the existing pathomorphologic
      changes.

PMID- 10933576
TI  - Effects of acute and chronic angiotensin receptor blockade on myocardial vascular
      blood volume and perfusion in a pig model of coronary microembolization.
AB  - Based on the reduction of ischemic cardiac events in clinical trials and
      experimental observations, inhibition of the effects of angiotensin II on
      coronary microcirculatory function may afford myocardial protection after injury.
      The immediate effects of intracoronary AT1 receptor blockade with irbesartan were
      examined in a pig model in the healthy myocardium and in acute ischemia induced
      by injection of 30-microm microspheres into the left anterior descending coronary
      artery (LAD). Electron-beam computed tomography was performed for in-vivo
      quantitative measurements of regional intramyocardial vascular blood volume
      (V(B)) and perfusion (F(M)), as well as left ventricular ejection fraction (LVEF)
      and muscle mass. Ratios of V(B) and F(M) in the anterior (LAD-supplied)/ inferior
      (control) myocardium were generated. At baseline, 0.2 mg/kg irbesartan injected
      into the LAD increased V(B) and F(M) ratios significantly by 27 +/- 8% and 51 +/-
      13%, respectively. After anterior coronary microembolization, V(B) and F(M)
      ratios were 0.60 +/- 0.05 and 0.51 +/- 0.05, respectively, and were significantly
      increased by irbesartan (by 24 +/- 10% and by 36 +/- 11%, respectively). After 4
      weeks of treatment with oral irbesartan (n = 7) or placebo (n = 7), an improved
      LVEF (56 +/- 4% v 44 +/- 4%, P = .046) was observed in irbesartan-treated
      animals, but no difference in LV end-diastolic volumes or muscle mass. Resting
      V(B) (0.95 +/- 0.06 v 0.76 +/- 0.06; P = .047) and F(M) (0.84 +/- 0.05 v 0.64 +/-
      0.04; P = .016) ratios were significantly greater in irbesartan-treated animals.
      Using adenosine, there was a trend for higher V(B) and F(M) ratios in irbesartan-
      v placebo-treated animals. Therefore, in a pig model of acute myocardial
      ischemia, AT1 receptor blockade by irbesartan induced microvascular vasodilation
      and, ostensibly, conveyed myocardial protection. Long-term treatment with
      irbesartan resulted in moderate enhancements of resting V(B) and F(M) compared
      with placebo, suggesting a role for coronary microcirculatory effects of chronic
      AT1 receptor blockade in preserving LVEF.

PMID- 10933578
TI  - Different association of hypertension and insulin-related metabolic syndrome
      between men and women in 8437 nondiabetic Chinese.
AB  - Insulin resistance may cause a metabolic syndrome but whether insulin resistance
      causes hypertension is very controversial. Furthermore, it remains unclear
      whether the link between the insulin-resistance-related metabolic syndrome and
      hypertension is different between men and women. We examined fasting insulin,
      glucose, triglyceride and high-density lipoprotein (HDL)-cholesterol levels,
      systolic blood pressure, body mass index, and waist-to-hip ratio in a dataset
      from 8437 nondiabetic residents (age range, 30 to 89 years) in Kinmen. Factor
      analysis, a multivariate correlation statistical technique, was used to
      investigate the clustering and interdependence of these risk variables. Factor
      analysis identified two factors for men (n = 3659) and three factors for women (n
      = 4778, respectively. In men, a cluster of insulin, triglyceride, HDL
      cholesterol, body mass index, and waist-to-hip ratio (metabolic syndrome)
      accounted for 29.7%, and a cluster of systolic blood pressure and glucose
      (hyperglycemia plus hypertension) accounted for 18.1% of the total variance in
      all variables considered. In women, a cluster of insulin, triglyceride, body mass
      index, waist-to-hip ratio, and systolic blood pressure (metabolic syndrome plus
      hypertension) accounted for 29.4%, a cluster of systolic blood pressure, glucose,
      and triglyceride (hyperglycemia plus hypertension plus dyslipidemia) accounted
      for 14.0%, and a cluster of triglyceride and HDL-cholesterol (dyslipidemia)
      accounted for 16.2% of the total variance. In conclusion, a distinct insulin
      resistance-related metabolic syndrome characterized by hyperinsulinemia,
      dyslipidemia, and obesity was observed for both men and women in this Chinese
      population. However, hypertension was linked to the metabolic syndrome in women
      only.

PMID- 10933579
TI  - Love those mice!

PMID- 10933580
TI  - Hepatitis C virus: evasion of the interferon-induced antiviral response.
AB  - Hepatitis C virus (HCV) is an emerging virus of great medical significance. A low
      drug-response rate and a high frequency of persistent infection have caused HCV
      to reach pandemic proportions. Many infected individuals go on to develop liver
      cirrhosis and hepatocellular carcinoma, and HCV is now the leading reason for
      liver transplants in the United States. Differences in genotype response to
      interferon therapy suggests that one or more viral genes may participate in
      evasion of the interferon-mediated cellular antiviral response. This review
      focuses on the viral genes that interact with the host cell to evade the
      interferon response and on the insights that these interactions may provide into
      HCV pathogenesis.

PMID- 10933581
TI  - Three-dimensional electron cryo-microscopy as a powerful structural tool in
      molecular medicine.
AB  - Electron cryo-microscopy has established itself as a valuable method for the
      structure determination of protein molecules, protein complexes, and cell
      organelles. This contribution presents an introduction to the various aspects of
      three-dimensional electron cryomicroscopy. This includes the need for sample
      preservation in the microscope vacuum, strategies for minimizing radiation
      damage, methods of improving the poor signal-to-noise ratio in electron
      micrographs of unstained specimens, and the various methods of three-dimensional
      image reconstruction from projections. The various specimen types (e.g., flat and
      tubular two-dimensional crystals, protein filaments, individual protein
      molecules, and large complexes) require different means of three-dimensional
      reconstruction, and we review the five major reconstruction techniques (electron
      crystallography, helical reconstruction, icosahedral reconstruction, single
      particle reconstruction, and electron tomography), with an emphasis on electron
      crystallography. Several medically relevant three-dimensional protein structures
      are chosen to illustrate the potential of electron cryo-microscopy and image
      reconstruction techniques. Among the structural methods, electron cryo-microscopy
      is the only tool for studying objects that range in size from small proteins over
      macromolecular complexes to cell organelles or even cells.

PMID- 10933582
TI  - Bid, a critical mediator for apoptosis induced by the activation of Fas/TNF-R1
      death receptors in hepatocytes.
AB  - The Bcl-2 family proteins consist of both antiapoptosis and pro-apoptosis members
      that regulate apoptosis typically at the mitochondrial level, mainly by
      controlling the release of cytochrome c and other mitochondrial apoptotic events.
      However, death signals mediated by Fas/TNF-R1 receptors can usually activate
      caspases directly, bypassing the need for mitochondria and escaping the
      regulation by Bcl-2 family proteins. Bid is a novel pro-apoptosis Bcl-2 family
      protein that is activated by Caspase 8 in response to Fas/TNF-R1 death receptor
      activation. Activated Bid is translocated to mitochondria and induces cytochrome
      c release, which in turn activates the downstream caspases. This Bid-mediated
      pathway is critical in hepatocyte apoptosis induced by Fas/TNF-R1 engagement,
      where direct activation of cytosolic caspase cascade seems inefficient. The
      dependence on Bid, and thus on the mitochondrial cytochrome c release, of
      hepatocyte apoptosis induced by the death receptors also renders it sensitive to
      the inhibitory regulation by the anti-apoptosis members of the Bcl-2 family
      proteins, such as Bcl-2 and Bcl-xL. Moreover, the revealing of this death pathway
      in hepatocytes is important to the understanding of the pathogenesis of a number
      of hepatic diseases such as hepatitis or endotoxemia-related hepatic failure.

PMID- 10933583
TI  - Rapid analysis of alpha1-antitrypsin PiZ genotype by a real-time PCR approach.
AB  - alpha1-Antitrypsin (AAT) deficiency is a common inherited cause of emphysema and
      cirrhotic liver disease. Current laboratory diagnosis of Pi (proteinase
      inhibitor) status by protein analysis depends on the availability of blood
      samples and has a limited accuracy. Single-strand conformational polymorphism
      (SSCP) analysis and direct DNA sequencing can be performed from blood cells or
      from tissue samples, but it is a time-consuming procedure not suitable for
      screening purposes. We used a Light-Cycler assisted PCR approach to identify the
      PiZ mutation and to determine hetero- and homozygous carrier status from whole
      blood and from paraffin-embedded archival tissue specimens. The results were
      compared to those obtained by standard PCR amplification followed by SSCP and
      direct DNA sequencing. Light-Cycler assisted PCR identified heterozygous PiZ
      mutations in 16 samples, a homozygous PiZ status in three cases, and wild-type
      PiM in five control samples. In all cases the results were confirmed by SSCP and
      direct DNA sequencing. Light-Cycler assisted PCR has a high detection rate for
      the PiZ mutation. It can be performed from blood or from fixed archival tissues,
      requires only small amounts of DNA, and allows a rapid diagnosis on a high output
      level.

PMID- 10933584
TI  - Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester
      hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins
      in mouse peritoneal macrophages.
AB  - We investigated the effect of endogenous apolipoprotein (apo) E synthesis in
      mouse peritoneal macrophages on cholesterol efflux and intracellular cholesteryl
      ester hydrolysis mediated by high-density lipoprotein-3 (HDL3) and lipid-free
      apolipoproteins (apo). After loading with acetylated LDL (acLDL) peritoneal
      macrophages from wild-type (apoE(+/+)) and apoE-deficient (apoE(-/-)) mice were
      incubated with medium alone or with liposomes, HDL3, lipid-free apoA-I, or lipid
      free apoE3. Cholesterol and cholesteryl esters in the cells and culture media
      were quantified by HPLC. Incubation of apoE(+/+) or apoE(-/-) macrophages for 18
      h with medium alone or with liposomes did not cause significant changes in
      cellular cholesterol. Addition of HDL3, apoA-I, or apoE3 to the medium led to
      significant cholesterol efflux, which was less efficient in apoE(-/-) macrophages
      than in apoE(+/+) macrophages. HDL and lipid-free apolipoproteins were more
      effective in reducing the cellular content of cholesteryl esters of apoE(+/+)
      macrophages than of apoE(-/-) macrophages, suggesting that endogenous apoE
      stimulates cholesteryl ester hydrolysis. The difference in the mass of
      cholesteryl esters was more pronounced for cholesteryl arachidonate and linoleate
      than for cholesteryl oleate or palmitate. Furthermore, in [(14)C]arachidonate
      labeling experiments cholesterol arachidonate hydrolysis was higher in apoE(+/+)
      macrophages than in apoE(-/-) macrophages in the presence of cholesterol efflux
      mediated by HDL3 or apoA-I. In contrast, in the absence of cholesterol efflux
      cholesterol arachidonate synthesis was higher in apoE(+/+) macrophages than in
      apoE-/- macrophages. Taken together, our data suggest that endogenous apoE
      stimulates cholesterol efflux and intracellular cholesteryl ester hydrolysis
      mediated by HDL3 and lipid-free apolipoproteins in mouse peritoneal macrophages.
      This may contribute to the antiatherogenic effect of apoE.

PMID- 10933585
TI  - Antisense prevention of neuronal damages following head injury in mice.
AB  - Closed head injury (CHI) is an important cause of death among young adults and a
      prominent risk factor for nonfamilial Alzheimer's disease. Emergency intervention
      following CHI should therefore strive to improve survival, promote recovery, and
      prevent delayed neuropathologies. We employed high-resolution nonradioactive in
      situ hybridization to determine whether a single intracerebro-ventricular
      injection of 500 ng 2'-O-methyl RNA-capped antisense oligonucleotide (AS-ODN)
      against acetylcholinesterase (AChE) mRNA blocks overexpression of the stress
      related readthrough AChE (AChE-R) mRNA splicing variant in head-injured mice.
      Silver-based Golgi staining revealed pronounced dendrite outgrowth in
      somatosensory cortex of traumatized mice 14 days postinjury that was associated
      with sites of AChE-R mRNA overexpression and suppressed by anti-AChE AS-ODNs.
      Furthermore, antisense treatment reduced the number of dead CA3 hippocampal
      neurons in injured mice, and facilitated neurological recovery as determined by
      performance in tests of neuromotor coordination. In trauma-sensitive transgenic
      mice overproducing AChE, antisense treatment reduced mortality from 50% to 20%,
      similar to that displayed by head-injured control mice. These findings
      demonstrate the potential of antisense therapeutics in treating acute injury, and
      suggest antisense prevention of AChE-R overproduction to mitigate the detrimental
      consequences of various traumatic brain insults.

PMID- 10933587
TI  - B-1 cells: the lineage question revisited.
AB  - The origins and functions of B-1 cells have sparked a good deal of controversy,
      largely centered on whether these B cells are developmentally distinct from the
      principal B cell populations (B-2) found in peripheral lymphoid organs. However,
      the prime criteria for assigning B-1 and B-2 cells to separate developmental
      lineages are satisfied by studies published some time ago that 1) identify
      distinct sources of progenitors for B-1 and B-2 cells; 2) show that these
      progenitors express their inherent commitment developing under the same
      conditions in co-transfer recipients; and, 3) have distinctive developmental
      patterns revealed by analysis of cells at various stages along the B-cell
      development pathway. I review these developmental studies here both to clarify
      the issue and to set the stage for presentation of evidence from more recent
      studies, which further define the functional differences between B-1 and B-2
      cells and reveal intriguing complexities in the selective and other mechanisms
      that control the V(H) composition of the B-1 antibody repertoire.

PMID- 10933588
TI  - B-cell commitment, development and selection.
AB  - Here we review three areas in B-cell development in the mouse, with a focus on
      relevance to B-1/CD5+ B cells. Multiparameter flow cytometry has allowed the
      dissection of intermediate stages of developing B cells, both in fetal liver and
      bone marrow. In the first area, we present recent work that has delineated a
      fraction of pre-pro-B cells, committed to the B lineage, but lacking any
      immunoglobulin rearrangements. Next, the role of the pre-B-cell receptor in B
      cell repertoire selection has become clear in the past few years, but we present
      work suggesting that the action of this process during fetal life is different,
      resulting in selection of a very distinct repertoire compared with adult.
      Finally, we describe a new VH3609 antithymocyte Ig transgenic mouse model system
      that has provided the first definitive evidence for the role of self-antigen in
      development and maintenance of natural autoreactive B cells.

PMID- 10933589
TI  - Repertoire selection by pre-B-cell receptors and B-cell receptors, and genetic
      control of B-cell development from immature to mature B cells.
AB  - During B-cell development the surrogate light (SL) chain is selectively expressed
      in progenitor and precursor B cells during the developmental stages of D(H) to
      J(H) and V(H) to D(H)J(H) rearrangements. Approximately half of all muH chains
      produced by these rearrangements cannot pair with SL chains and cannot form a pre
      B-cell receptor (pre-BCR). A spectrum of affinities between VpreB and individual
      V(H) domains generates preB cells with pre-BCR of different fitness which, in
      turn, determines the extent of the pre-B II-cell proliferation and the fidelity
      of allelic exclusion of the H chain locus. Once pre-BCR is expressed, SL chain
      expression is turned off. As pre-B II cells proliferate, SL is diluted out, thus
      limiting pre-BCR formation. As a consequence, pre-B II cells stop proliferating,
      become small and resting and begin to rearrange the L chain loci. Multiple
      rearrangements of the kappaL chain alleles are often detected in wild-type small
      pre-B II cells. Around 20% of the muH chain-expressing small pre-B II cells also
      express L chains but do not display the Ig on the surface. Hence, it is likely
      that not all L chains originally generated in resting pre-B II cells can pair
      with the muH chain previously present in that cell. The best fitting ones are
      selected preferentially to generate sIg+ B cells. Furthermore, the transition of
      immature B cells from the bone marrow to spleen and their development to mature
      cells appear as two separate steps controlled by different genes.

PMID- 10933590
TI  - The role of the preBCR, the interleukin-7 receptor, and homotypic interactions
      during B-cell development.
AB  - Considerable progress has been made in defining intermediate stages in the
      process leading from stem cells to mature B cells. Cell-bound and secreted
      molecules direct the progression through these stages and regulate the selection
      of clones from which the immune repertoire emerges. In fact, a myriad of signals
      derived from B-cell progenitors themselves and the microenvironment in which they
      develop direct the differentiation process. These signals are provided by B-cell
      antigen receptors (BCR) and their surrogates, and by adhesion and cytokine
      receptors. The co-operation of these receptors to control survival, expansion,
      and differentiation of early B-cell progenitors is the topic of this review.
      Specifically, we will summarize recent findings from our laboratory demonstrating
      that preBCR expression lowers the threshold for interleukin (IL)-7
      responsiveness. How signals initiated by these receptors may intersect at this
      critical point of B-cell selection will be discussed. At the stage following IL-7
      responsiveness we have shown that interactions between B-cell progenitors
      themselves promote their differentiation to immunoglobulin-secreting B cells. We
      propose that one function of stromal cells, known to be central to B
      lymphopoiesis, is to promote critical preB-preB homotypic interactions and
      ensuing signals.

PMID- 10933591
TI  - B-cell repertoire formation: role of the recombination signal sequence in non
      random V segment utilization.
AB  - V, D, and J gene segments rearrange at different frequencies in vivo. Each
      rearranging gene segment is flanked by a recombination signal sequence (RSS),
      which is composed of a conserved heptamer and nonamer, separated by a spacer of
      conserved length but not conserved sequence. We summarize data from our lab and
      other labs showing that in many cases, but not all, the RSS can account for
      differences in recombination frequencies observed in vivo. Our approach is to
      determine the initial frequency of rearrangement of the V genes in vivo, and then
      place the RSSs of two V genes into a competition recombination substrate to
      determine the relative frequency with which the two RSSs support recombination.
      In one example, we have shown that a polymorphism in the heptamer of a Vkappa
      gene can result in a significant reduction in recombination frequency. This
      particular allele is prevalent in Navajos and absent in other populations. We
      suggest that this single change may play a major role in the high susceptibility
      of Navajos to Haemophilus influenzae infection, since this Vkappa gene is
      important in the antibody response to this bacteria. We also describe experiments
      showing that the sequence of the spacer of the RSS can play an important role in
      relative recombination frequencies.

PMID- 10933592
TI  - B-cell subsets and the mature preimmune repertoire. Marginal zone and B1 B cells
      as part of a "natural immune memory".
AB  - The rate of elimination of a pathogenic agent is of critical importance for the
      host and determines the extent and consequences of the infection. Antibody
      production, along with the activity of other cells of the immune system, plays an
      important role early and late in the response and contributes to all containment
      and elimination of the organism. B-cell clones reaching the mature long-lived
      pool are heterogeneous: some belong to the B1 B-cell subset, some are enriched in
      the CD21high compartment (mostly marginal zone (MZ)), whereas others recirculate
      primarily among the B-cell follicles (FO). This segregation is a T-independent,
      CD40L-independent but BCR/CD19-dependent process. Antigen encounter will recruit
      antigen-specific cells from the pool of mature B-lymphocytes and activate them to
      perform effector functions. CD21highCD23low B cells enriched in the MZ of the
      spleen initiate the early plasmablast wave during the first 3 days of an antibody
      response against particulate T-independent bacterial antigens. These findings
      indicate a functional heterogeneity within the mature B-lymphocyte population. MZ
      B cells and B1 B, in contrast to FO B cells, have the unique capacity to generate
      effector cells in early stages of the immune response against (particulate)
      antigens that are scavenged efficiently in these specialized anatomical sites.

PMID- 10933593
TI  - Pre-B and pre-T-cell receptors: conservation of strategies in regulating early
      lymphocyte development.
AB  - Early lymphocyte development is characterized by the regulated activity of the
      V(D)J recombinase and the positive and negative selection of cells based on the
      structure of their assembled antigen receptor genes. Developing B and T cells use
      remarkably similar signaling complexes, the pre-B-cell receptor (pre-BCR) and the
      pre-T-cell receptor (pre-TCR) respectively, to monitor the progress of antigen
      receptor gene assembly This review will compare and contrast the regulation and
      activities of the pre-BCR and pre-TCR signaling complexes. In addition, we will
      consider a number of critical but as yet unanswered questions prompted by such an
      analysis.

PMID- 10933594
TI  - Transcriptional regulation of early B-lymphocyte differentiation.
AB  - Differentiation of hematopoietic progenitors into the B-lymphocyte lineage
      requires co-ordination of a complex network of transcriptional regulators.
      Lineage specificity is likely to result from combinatorial mechanisms of gene
      regulation. Four general functions are mediated by transcription factors in the
      differentiating pro-B cell. First, a cascade of B-cell-restricted transcription
      factors is upregulated. Second, genes involved in the specification of other cell
      fates are repressed. Both activation and repression require the participation of
      different classes of transcriptional regulators, including proteins of the Ikaros
      family that can recruit chromatin-modifying complexes. Third, the expression of
      genes that facilitate B-cell proliferation and differentiation are activated.
      Lastly, genes required for recombination are expressed and targeted to the
      immunoglobulin loci, thus initiating the characteristic rearrangement of the
      immunoglobulin genes. The interactions and functions of transcription factors in
      pro-B-cell differentiation are discussed.

PMID- 10933595
TI  - Fidelity and infidelity in commitment to B-lymphocyte lineage development.
AB  - During B-lymphocyte development in mouse fetal liver and bone marrow, a pre-B I
      cell stage is reached in which the cells express B-lineage-specific genes, such
      as CD19, Ig alpha and Igbeta and VpreB and lambda5, which encode the surrogate
      light (SL) chain. In these pre-B I cells both alleles of the immunoglobulin heavy
      (IgH) chain locus are D(H)J(H) rearranged. Transplantation of pre-B I cells from
      wild-type (e.g. C57Bl/6) mice in histocompatible RAG-deficient hosts leads to
      long-term reconstitution of some of the mature B-cell compartments and to the
      establishment of normal IgM levels, a third of the normal serum IgA levels, and
      IgG levels below the detection limit. Neither T-lineage nor myeloid cells of
      donor origin can be detected in the transplanted hosts, indicating that the pre-B
      I cells are committed to B-lineage differentiation. Consequently, the B-cell
      reconstituted hosts respond to T-cell-independent antigens but not to T-cell
      dependent antigens. Responses to T-cell-dependent antigens can be restored in the
      pre-B I-cell-transplanted, RAG-deficient hosts by the concomitant transplantation
      of mature CD4+ T cells. The transplanted wild-type pre-B I cells do not home back
      to the bone marrow and become undetectable shortly after transplantation. B
      lymphocyte development in Pax-5-deficient mice becomes arrested at the transition
      of pre-B I to pre-B II cells i.e. at the stage when V(H) to D(H)J(H)
      rearrangements occur and when the pre-B-cell receptor, complete with muH chains
      and SL chains, is normally formed. T-lineage and myeloid cell development in
      these mice is normal. Pre-B I cells of Pax-5-deficient mice have a wild-type pre
      B I-cell-like phenotype: while they do not express Pax-5-controlled CD19 gene,
      and express Ig alpha to a lesser extent, they express Igbeta, VpreB and lambda5,
      and proliferate normally in vitro on stromal cells in the presence of interleukin
      (IL)-7. Clones of these pre-B I cells carry characteristic D(H)J(H)
      rearrangements on both IgH chain alleles. However, removal of IL-7 from the
      tissue cultures, unlike wild-type pre-B I cells, does not induce B-cell
      differentiation to surface IgM-expressing B cells, but induces macrophage
      differentiation. This differentiation into macrophages requires either the
      presence of stromal cells or addition of macrophage colony-stimulating factor (M
      CSF). Addition of M-CSF followed by granulocyte-macrophage colony-stimulating
      factor induces the differentiation to MHC class II-expressing, antigen-presenting
      dendritic cells. In vitro differentiation to granulocytes and osteoclasts can
      also be observed in the presence of the appropriate cytokines. Moreover,
      transplantation of Pax-5-deficient pre-B I clones into RAG-deficient hosts, while
      not allowing B-cell differentiation, leads to the full reconstitution of the
      thymus with all stages of CD4-CD8- and CD4+CD8+ thymocytes, to normal positive
      and negative selection of thymocytes in the thymus, and to the development of
      normal, reactive mature CD4+ and CD8+ T-cell compartments in the peripheral
      lymphoid tissues, all carrying the clone-specific D(H)J(H) rearrangements. On the
      other hand, Ig alpha, Igbeta, VpreB and lambda5 are turned off in the thymocytes,
      demonstrating that the expression of these genes does not commit cells
      irreversibly to the B lineage. Further more, Pax-5-deficient pre-B I cells are
      long-term reconstituting cells. They home back to the bone marrow of the RAG
      deficient host, can be reisolated and regrown in tissue culture, and can be
      retransplanted into a secondary RAG-deficient host. This again develops
      thymocytes and mature T cells and allows the transplanted clonal pre-B I cells to
      home to the bone marrow.

PMID- 10933596
TI  - All B cells are progeny of endothelial cells: a new perspective.
AB  - We present here a speculative view of embryonic hematopoiesis. We do this with
      the hope of finding directions for future study, keeping in mind that our model
      may diverge from the real situation. However, we want to emphasize that previous
      models have neglected the possibility that endothelial cells (EC) represent a
      progenitor of hematopoietic cells (HPC). Emerging evidence, including our own,
      and previous histological studies argue for the presence of hemogenic EC. We
      discuss seemingly contradictory points of view of embryonic hematopoiesis, such
      as the origin of lymphogenic progenitors, and have shown that they may be
      resolved more satisfactorily by introducing this notion. Obviously, a good model
      should be a testable one, so we are currently developing experimental systems to
      demonstrate that all B cells are, indeed, the progeny of EC.

PMID- 10933597
TI  - The role of Bruton's tyrosine kinase in B-cell development and function: a
      genetic perspective.
AB  - Mutations in Bruton's tyrosine kinase (Btk) result in the B-cell
      immunodeficiencies X-linked agammaglobulinemia in humans and X-linked
      immunodeficiency in mice. These diseases are characterized by blocks in B-cell
      development at multiple stages and impaired function of residual mature B cells.
      This review focuses on a series of in vivo genetic studies that have begun to
      define the mechanism by which Btk regulates B-cell development and function. The
      functional interactions between Btk and other signaling molecules defined by this
      approach are more complex than initially appreciated from in vitro biochemical
      and cell culture studies.

PMID- 10933598
TI  - Early B-lymphocyte precursors and their regulation by sex steroids.
AB  - This review describes an improved characterization of early B-lymphocyte
      precursors in mice and the remarkable sensitivity of the same cells to hormones.
      The nuclear enzyme terminal deoxynucleotidyl transferase (TdT) was used as a
      marker to image and characterize bone marrow cells lacking all lineage-associated
      markers. Most early TdT+ precursors have a distinctive density of c-kit and
      express the interleukin-7Ralpha chain, as well as flt-3/flk2, but lack CD34. An
      understanding of those cell surface properties made it possible to obtain highly
      enriched, viable cells with the potential to give rise to CD19+ lymphocytes in
      culture. A series of other flow cytometry and culture experiments suggested a
      possible differentiation sequence for these early pro-B cells. This new model was
      used to advantage in our studies of sex steroids. It appears that early
      precursors represent a hormone-sensitive control point for determining numbers of
      new B lymphocytes that are produced within bone marrow. We also compare and
      contrast these findings with B lymphopoiesis in humans.

PMID- 10933599
TI  - E2A proteins: essential regulators at multiple stages of B-cell development.
AB  - The development of mature B lymphocytes from multipotent progenitor cells
      requires the co-ordinated activities of a number of transcriptional regulatory
      proteins. The transcription factors encoded by the E2A gene are required for the
      development of committed B-lineage cells and regulate the expression of essential
      B-lineage genes at multiple stages of differentiation and activation. In this
      review we discuss the evidence that the E2A gene products function in the
      regulation of 1) transcription factors required for B-lineage determination, 2)
      essential proteins involved in pro-B and pre-B-cell development, 3) accessibilty
      and recombination of the IgH and IgL chain loci, and 4) isotype switching in
      activated, mature B lymphocytes.

PMID- 10933600
TI  - Terminal deoxynucleotidyl transferase and repertoire development.
AB  - In mice, the absence of terminal deoxynucleotidyl transferase (Tdt) expression
      during fetal and neonatal life provides a window in development where clones of
      lymphocytes are generated that provide protective immunity. Introducing premature
      Tdt activity interferes with the development of these clones and results in an
      impaired ability to make protective antibodies. Conversely, gene-targeted
      disruption of Tdt prevents N additions at all stages of T and B-lymphocyte
      development and promotes the development of fetal-like T and B-cell clones into
      adulthood, with accompanying alterations in repertoire. The alternative splice
      forms of Tdt may be necessary to provide regulatory mechanisms to restrict N
      addition to appropriate stages of the developmental pathways, the details of
      which are being revealed. The evidence continues to build that Tdt is a key
      player in influencing the outcome of V(D)J recombination during lymphocyte and
      repertoire development.

PMID- 10933601
TI  - Apoptosis and its modulation during B lymphopoiesis in mouse bone marrow.
AB  - Studies in normal, gene-deleted, transgenic and mutant mice have examined
      apoptotic cell death and its role in B lymphopoiesis in bone marrow. Apoptotic
      activity has been quantitated among phenotypically defined populations of
      precursor B cells using flow cytometry of apoptotic cells and an established
      model of B-cell development. In normal mice, the frequencies of apoptotic cells
      (apoptotic index) and accumulation of apoptotic cells during short-term culture
      (apoptotic rate) are maximal at around the pro/pre-B-cell transition and among
      immature B lymphocytes. The brief period between onset of apoptosis and clearance
      by macrophages (apoptotic transit time) is similar for most precursor B-cells.
      Apoptosis-modulating factors produce substantial changes in apoptotic activity
      among pro-B and pre-B cells, associated with altered expression of bcl-2 family
      proteins. Pro-B-cell apoptosis, normally extensive, is markedly suppressed in the
      absence of p53. Complete pro-B-cell abortion in RAG-2 deletion provides an assay
      for apoptotic fractions in other experimental systems. Pre-B-cell apoptosis is
      enhanced by deficiencies of interleukin (IL)-7, Abl protooncogene or colony
      stimulating factor (CSF)-1 and overexpression of heat-stable antigen, and is
      inhibited by IL-7 and p190bcr/abl transgenes. CSF-1 and melatonin administration
      inhibit pre-B-cell apoptosis, probably via stromal cell stimulation. Such
      apoptotic modulation has implications for B-cell homeostasis, quality control,
      immunodeficiency and neoplasia.

PMID- 10933603
TI  - The chicken B-cell receptor complex and its role in avian B-cell development.
AB  - The bursa of Fabricius is critical to normal B-lymphocyte development in birds.
      During embryonic life, B-cell precursors migrate to the bursal rudiment and those
      which have undergone productive V(D)J recombination colonize lymphoid follicles
      and undergo immunoglobulin V gene diversification by gene conversion. The chicken
      surface IgM complex appears structurally and functionally equivalent to its
      mammalian counterpart, with homologs to CD79a and CD79b. Expression of a
      truncated Igmu chain is sufficient to drive the early stages of B-cell
      development in the embryo bursa. Bursal cells expressing the truncated mu
      receptor complex proliferate in bursal follicles, and those which contain V gene
      rearrangements undergo V gene diversification by gene conversion. The bursa is a
      gut-associated organ and antigen is focused to bursal lymphoid follicles after
      hatch. While expression of the truncated mu chain is sufficient to support B-cell
      development in the embryo, B cells expressing this receptor are rapidly
      eliminated after hatch. We suggest the possibility that B-cell development in the
      bursa after hatch is driven by encounter with antigen leading to redistribution
      of B cells within the lymphoid follicle, B-cell proliferation and V gene
      repertoire development by gene conversion.

PMID- 10933602
TI  - Microenvironmental influences on human B-cell development.
AB  - Mammalian B-cell development can be viewed as a developmental performance with
      several acts. The acts are represented by checkpoints centered around commitment
      to the B-lineage and functional Ig gene rearrangement--culminating in expression
      of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through
      these checkpoints is profoundly influenced by the fetal liver and adult bone
      marrow (BM) stromal cell microenvironments. Our laboratory has developed a model
      of human B-cell development that utilizes freshly isolated/non-transformed human
      BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem
      cells plated in this human BM stromal cell microenvironment commit to the B
      lineage and progress through the pre-BCR and BCR checkpoints. This human BM
      stromal cell microenvironment also provides survival signals that prevent
      apoptosis in human B-lineage cells. Human B-lineage cells exhibit differential
      expression of Notch receptors and human BM stromal cells express the Notch ligand
      Jagged-1. These results suggest a potential role for Notch in regulating B
      lineage commitment and/or progression through the pre-BCR and BCR checkpoints.

PMID- 10933604
TI  - B-cell development in the amphibian Xenopus.
AB  - The amphibian Xenopus and mammals have similar organization and usage of their
      immunoglobulin gene loci with combinatorial joining of V, D and J elements. The
      differences in B-cell development between mammals and this amphibian are due to
      major differences in developmental kinetics, cell number and lymphoid organ
      architecture. Unlike mammals, the immune system of Xenopus develops early under
      pressure to develop quickly and to produce a heterogeneous repertoire before
      lymphocyte numbers reach 5,000, thereby imposing a limitation on clonal
      amplification. In addition, it is submitted to metamorphosis. Thus, during the
      early antigen-independent period, several features of B-cell development related
      to immune diversification are under strict genetically preprogramed control: 1) D
      reading frames contribute complementary determining region 3 with features that
      occur in mammals by somatic selection, 2) the temporal stepwise utilization of
      V(H) genes in Xenopus occur in families probably because of structural DNA
      features rather than their position in the locus. Larval and adult immune
      responses differ in heterogeneity. Larval rearrangements lack N diversity. During
      the course of immune responses, somatic mutants are generated at the same rate as
      in other vertebrates but are not optimally selected, probably due to the simpler
      organization of the lymphoid organs, with neither lymph nodes nor germinal
      centers resulting in poor affinity maturation. Switch from IgM to other isotypes
      is mediated by loop-excision deletion of the IgM constant region gene via switch
      regions which, unlike their mammalian counterpart, are A-T rich and reveal
      conserved microsites for the breakpoints.

PMID- 10933605
TI  - Development of the antibody repertoire in rabbit: gut-associated lymphoid tissue,
      microbes, and selection.
AB  - Rabbits generate their antibody repertoire in three stages. First, a neonatal
      repertoire is generated by B lymphopoiesis in fetal liver and bone marrow and is
      limited by preferential V(H) gene segment usage. Between 4 and 8 weeks after
      birth a complex primary antibody repertoire is developed by somatically
      diversifying the neonatal repertoire through somatic hypermutation and a somatic
      gene conversion-like mechanism in gut-associated lymphoid tissue (GALT). In
      rabbits, unlike other species, the development of the primary antibody repertoire
      through somatic diversification of Ig genes appears to be dependent on intestinal
      microbial flora. The primary antibody repertoire is subsequently modified during
      antigen-dependent immune responses in which VDJ genes further diversify both by
      somatic hypermutation and by a gene conversion-like mechanism (the secondary
      repertoire). During the various stages of development, the antibody repertoire is
      modified and shaped by selective processes. In this review, we discuss the roles
      of GALT, microbes, and B-cell selection in generating antibody diversity in
      rabbits.

PMID- 10933606
TI  - Role of natural killer cells in iscador mediated inhibition of metastasis by
      adoptive immunotherapy.
AB  - Iscador activated (in vivo and in vitro) splenocytes were found to inhibit
      metastatic tumour growth in C57BL/6 mice. In order to check whether NK cells are
      involved in the antimetastatic activity of Iscador activated splenocytes ,animals
      were depleted of NK cells using antiasialo GMI antibodies. When spleen cells
      activated in vivo with Iscador were injected into animals pretreated with
      Antiasialo GM I antibodies, there was an average of 44.6 tumour nodules on 21st
      day indicating that stimulation of NK cell activity produced by the Iscador
      compensate for the NK cell depletion by Antiasialo GM I antibody. Animals treated
      with Iscador activated splenocytes showed an average survival period of 68 days
      whereas that of control tumour bearing animals treated with Ab the average
      survival was 19.3 days. The lung collagen hydroxyproline content, serum sialic
      acid levels, markers of metastasis were also significantly (P<0.001) lowered in
      these animals compared to those of the untreated tumour bearing animals. gamma
      glutamyl transpeptidase a marker of neoplastic growth, was also significantly
      reduced (P<0.001) in animals treated with activated splenocytes.

PMID- 10933607
TI  - Aminoguanidine-induced amelioration of autoimmune encephalomyelitis is mediated
      by reduced expression of inducible nitric oxide synthase in the spinal cord.
AB  - To elucidate whether an inducible nitric oxide synthase (iNOS) inhibitor,
      aminoguanidine (AMG), affects the expression of iNOS in the spinal cords of rats
      with experimental autoimmune encephalomyelitis (EAE), we induced EAE in Lewis
      rats, and treated EAE rats with AMG. AMG (200mg/kg administered intraperitoneally
      from day 0 to day 7 post-immunization) significantly reduced the clinical
      severity of EAE paralysis. AMG, however did not prevent the occurrence of EAE.
      Western blot analysis showed that iNOS expression was significantly reduced in
      the spinal cords of rats with EAE treated with AMG compared with rats treated
      with the vehicle. This finding supports the conclusion that the production of
      nitric oxide by iNOS plays an important role in the induction of EAE. The
      corollary is that the amelioration of EAE paralysis by the treatment with AMG is
      associated with the suppression of iNOS expression in the target organ i.e. the
      spinal cord.

PMID- 10933608
TI  - IL-12 reverses established tolerance mediated by TCRalphabeta+ but not by
      TCRgammadelta+ suppressor T cells.
AB  - Topical cutaneous painting with chemically reactive haptens induces the ability
      to subsequently elicit contact sensitivity (CS) responses in the skin. These CS
      responses are in vivo examples of acquired, antigen (Ag)-specific T cell
      immunity, and are a form of delayed-type hypersensitivity (DTH). In contrast,
      high dose i.v. administration of the hapten can induce Ag-specific tolerance. In
      some instances this specific immune hyporeactivity is due to suppressor T cells.
      We investigated the effect of IL-12 on reversal of tolerance due to suppressor T
      cells that were induced by i.v. administration of hapten in either normal
      TCRalpha+/+, or in immunodeficient TCRalpha-/- mice. In the TCRalpha+/+ mice,
      tolerance is mediated by TCRalphabeta+ suppressor T cells, while in the TCRalpha
      /- mice the tolerance is due to suppressive TCRgammadelta+ cells. Treatment with
      IL-12 reversed suppressor mediated by the TCRalphabeta+ cells, but did not affect
      tolerance due to TCRgammadelta+ suppressor cells. Another difference was that the
      alphabetaTCR+ suppressor cells produced a soluble suppressor factor that could
      replace the surppressor cells, while gammadeltaTCR+ suppressor cells did not. We
      hypothesized that IL-12 may strengthen responses of target CS-effector T cells
      influenced by the hapten-MHC-specificity of alphabeta suppresssor cells, or
      suppressor factor. On the other hand, gammadeltaTCR+ suppressive cells likely
      have specificity for the hapten alone, and are not MHC-restricted, and therefore
      probably do not operate via peptide-MHC interactions, that could be strengthened
      by IL-12. The ability of IL-12 to strengthen the resistance of CS-effector T
      cells to alphabeta TCR suppressor cells, may be due to the ability of IL-12 to
      increase T cell costimulation mediated by signaling mechanisms acting via B7.1
      and B7.2. In contrast, gammadeltaTCR+ suppressor cells, that are largely hapten
      specific, probably do not interact with peptide/MHC complexes on APC, and thus
      are not affected by IL-12 strengthening of co-stimulation.

PMID- 10933609
TI  - IFN-gamma inhibits the suppressive effects of PGE2 on the production of tumor
      necrosis factor-alpha by mouse macrophages.
AB  - Tumor necrosis factor-alpha (TNF-alpha) has become known as a central mediator of
      responses to endotoxin, rheumatoid diseases, and other forms of inflammation.
      Current investigations indicate that the production of TNF-alpha is controlled by
      other mediators, including interferon-gamma (IFN-gamma) and prostaglandin E2
      (PGE2). In the present study, we investigated the regulatory effects of IFN-gamma
      and/or PGE2 on LPS-induced TNF-alpha production and mRNA expression in mouse
      peritoneal macrophages using the enzyme immunoassay and Northern blot analysis,
      respectively. In response to 10 ng/ml of LPS, TNF-alpha production reached a
      maximum at approximately 4 hrs, followed by rapid decline. At the molecular
      level, TNF-alpha mRNA accumulated rapidly after LPS exposure, reaching a peak by
      3 hr, and declined more rapidly than did the production of TNF-alpha. Exposure of
      macrophages to 100 U/ml of IFN-gamma caused an increase in both the TNF-alpha
      production and mRNA expression induced by LPS. Exogenous PGE2 caused a dose
      dependent reduction in LPS-induced TNF-alpha mRNA accumulation as well as TNF
      alpha production. Macrophages primed with IFN-gamma showed the reduced
      responsiveness to the suppressive effect of PGE2 on the production of TNF-alpha
      and the accumulation of TNF-alpha mRNA. These findings indicate that the
      suppressive effects induced by PGE2 on the accumulation of TNF-alpha mRNA as well
      as the production of TNF-alpha can be reduced by the pretreatment of macrophages
      with IFN-gamma. These studies demonstrate the role of IFN-gamma as an
      immunomodulating compound that may effectively regulate TNF-alpha production by
      modulation of macrophage responsiveness to PGE2.

PMID- 10933611
TI  - B cells from autoimmune BXSB mice are hyporesponsive to signals provided by CD4+
      T cells.
AB  - Male BXSB mice, unlike female BXSB mice, develop an early-onset, lupus-like
      disease characterized by high levels of anti-nuclear antibodies (Abs) and total
      Ig. It has recently been shown that the male BXSB mice contain an expanded
      population of large B cells which are hyperresponsive to stimulation by anti-CD40
      mAb. The present study was undertaken to determine whether their potential for
      extra CD40 signaling enabled the B cells from male BXSB mice to hyper-respond to
      CD40L-expressing CD4+ T cells. In contrast to expectations, large B cells from
      male BXSB mice did not interact with CD4+ T cells in a positive manner; cultures
      of B cells from antigen (Ag)-primed male BXSB mice, unlike cultures of B cells
      from Ag-primed female mice, generated few antibody forming cells (AFC) following
      interaction with activated CD4+T cells. In addition, B cells from male BXSB mice,
      unlike B cells from female BXSB mice, failed to upregulate MHC class II molecules
      following interaction with activated CD4+ T cells. Subsequent experiments
      revealed that the inability of the B cells from the male mice to upregulate MHC
      class II molecules in response to T cell-mediated activation resided primarily in
      the population of large B cells. Large B cells from male BXSB mice were also
      defective in their ability to proliferate following stimulation with activated
      CD4+ T cells. Taken together, these findings demonstrated that similar to B cells
      in lupus patients, large B cells from male BXSB mice could function in a
      hyporesponsive manner, and that this hyporesponsiveness related to the inability
      of the B cells to interact in a positive manner with CD4+T cells.

PMID- 10933610
TI  - Cytokine regulation of CD44 expression on rat intestinal epithelial cells.
AB  - CD44 comprises a family of type I transmembrane glycoproteins that is expressed
      on a wide range of cells including those of epithelial, lymphoid and myeloid
      lineage. Although expression of CD44 in the small intestine is typically
      localised in the crypts of Lieberkuhn, we have reported the expression of CD44 on
      mature, intestinal villus epithelial cells during the development of small bowel
      allograft rejection. The mechanisms underlying CD44 up-regulation are unknown,
      although it may be influenced by localised cytokine production. This study used
      flow cytometry to assess the effects of recombinant IFN-gamma and TNF-alpha on
      CD44 expression and hyaluronan binding by the rat small intestinal epithelial
      cell lines, RIE and IEC 6. IFN-gamma upregulated CD44 expression on RIE (155% of
      unstimulated control) and IEC 6 (209% of unstimulated control) cells, whereas TNF
      alpha had no effect. IFN-gamma had no qualitative effect on CD44, as binding of
      the ubiquitously expressed extracellular matrix polysaccharide hyaluronan was
      unchanged. RIE and IEC 6 cells expressed the 82 kDa and 130 kDa major isoforms of
      CD44, however cytokine stimulation did not affect the expression of these, nor
      did stimulation induce the expression of other variants. In summary, these
      findings demonstrate that CD44 expression by intestinal epithelial cells can be
      regulated by cytokines, yet their ability to bind hyaluronan and the isoform of
      the expressed CD44 remains unaltered. It appears that localised inflammatory
      conditions and cytokine production may modify epithelial cell expression of CD44,
      however the physiological role for such a response has yet to be elucidated.

PMID- 10933613
TI  - Simplified method to generate large quantities of dendritic cells suitable for
      clinical applications.
AB  - The present study describes the optimization of an in vitro culture method for
      generating large amounts of dendritic cells (DC) in serum-free conditions from
      leukapheresis containing a mixed population of peripheral blood mononuclear cells
      (PBMC) which are cultured in the presence of GM-CSF and IL-13. Initial
      comparisons between the generation of DC from bulk and monocyte-enriched
      leukapheresis products showed that the presence of lymphocytes during the culture
      favors the differentiation of monocytes into DC. DC yields obtained from mixed
      mononuclear cell cultures were between 38 and 54% higher than yields obtained
      from monocyte-enriched cultures. Both types of cultures resulted in the
      generation of DC with an immature phenotype (CD83- and high phagocytic activity),
      which have been previously shown to be good stimulators for T cell responses. DC
      yields of bulk cultures in serum-free conditions were significantly higher than
      those obtained in the presence of 2% human serum. The cytokines of the
      supernatants of serum-free cultures comprised a significant content of pro
      inflammatory cytokines such as IL-1, IL-12 and TNF-alpha. Maturation of DC
      generated by this method can be induced by treatment with double-stranded RNA,
      LPS or TNF-alpha, resulting in enhanced surface expression of CD80, CD86, CD40,
      CD83 and MHC molecules on the DC. The methodology described here offers the
      possibility for generating large amounts of clinical grade DC from bulk
      leukapheresis products, thus avoiding DC precursor purification steps, and
      thereby minimizing the risks of contamination. This culture process may be
      applied to cell-based therapeutic approaches for the treatment of cancer or
      chronic viral infections.

PMID- 10933612
TI  - Induced minor malformations in the neocortex of normal mice do not alter
      immunological functions.
AB  - The interactive relationship between the CNS and the immune system is well
      established. Major lesions in the brain have been shown to affect immune
      response. However, whether minor, focal lesions (ectopias), as seen in autoimmune
      mice, may induce alterations in the immune system is unknown. To address this
      point, ectopic lesions in the neocortex were induced in neonatal DBA/2 mice
      (Induced minor malformations; IMM) and their immune capabilities were assessed at
      adulthood. Serum was collected from each animal and analyzed for the presence of
      autoantibodies. In addition, splenic lymphocytes and thymocytes were collected to
      ascertain proliferative capabilities and to assess for possible phenotypic
      changes in lymphocyte subsets. Mice with IMM did not manifest IgG autoantibodies
      against cardiolipin, dsDNA or brain membrane antigens. Total lymphocyte
      cellularity was not affected. The induction of cerebrocortical ectopias did not
      impair the ability of splenic and thymic lymphocytes to proliferate in response
      to anti-CD3 antibodies or Concanavalin-A (Con-A) as determined by non-radioactive
      (Alamar Blue) and radioactive (3H-thymidine) assays. Moreover, no difference in
      proliferation of unstimulated and anti-CD3-stimulated splenic lymphocytes exposed
      to rIL-2 or rIL-7 was observed. Flow cytomeric analysis of a variety of cell
      surface antigens, indicated that there was no difference in lymphocyte subsets
      between control and IMM groups. Therefore, we conclude that induced IMM lesions
      in the CNS of normal DBA/2 mice do not alter immune functions.

PMID- 10933614
TI  - Detection of antibodies to gangliosides and glycolipids in various intravenous
      immunoglobulin (IVIg) preparations.
AB  - The aim of this study was to examine the presence of antibodies to GM1 and
      sulfatide in various IVIg preparations. Five brands of commercially available
      human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and
      compared. Serial dilutions of each of the above preparations were prepared at a
      working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well
      microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid
      sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin,
      Isiven), except for Cutter IVIg, contained low to medium titers of the
      autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies
      to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and
      Isiven contained only low-titer of autoantibodies to sulfatide. The presence of
      natural autoantibodies to myelin in human sera may explain the presence of the
      tested antibodies within IVIg preparations. Measurements of antibodies to
      ganglioside and glycolipid in sera of Guillain-Barre patients immediately
      following IVIg, would probably not reveal antibody decrease. Alternatively, long
      term (several weeks) follow-up of titers might result in their modification due
      to inhibition of antibodies production by IVIg.

PMID- 10933615
TI  - Change in transaminases in hepatitis C virus- and HIV-coinfected patients after
      highly active antiretroviral therapy: differences between complete and partial
      virologic responders?
AB  - Patients with HIV and hepatitis C virus (HCV) coinfection have more severe
      hepatitis-related disease than do patients with HCV infection alone. Highly
      active antiretroviral therapy (HAART) with protease inhibitor appears to restore
      pathogen-specific immune responses, especially in patients with persistent
      undetectable HIV viral load. To evaluate the potent impact of immune restoration
      induced by HAART on the course of HCV-related disease, HCV viremia and levels of
      transaminases were compared between two groups of patients: 10 HIV/HCV-coinfected
      patients with persistently undetectable HIV viremia (group A) and 12 HIV/HCV
      coinfected patients with persistent detectable HIV viremia. No difference was
      detected in HCV viral load in either group. An increase in transaminases was
      found only in patients with persistent undetectable HIV viral load, which was
      correlated with the increase in CD8+ T cells. This may suggest that the
      restoration of CD8+ T cell cytotoxicity could lead to an enhancement of hepatitis
      C-related disease in HCV/HIV-coinfected patients receiving HAART.

PMID- 10933616
TI  - Substantial correlation between HIV type 1 drug-associated resistance mutations
      in plasma and peripheral blood mononuclear cells in treatment-experienced
      patients.
AB  - The correlation of detectable HIV-1 drug resistance mutations in plasma and PBMCs
      in patients extensively treated with all antiretroviral drug classes has not been
      fully elucidated. The detection of mutations in PBMCs may reveal resistant HIV-1
      associated with past therapies. In addition, these measures in PBMCs may have a
      practical value when plasma virus is at low levels that are difficult to detect
      with current assays. The reverse transcriptase (RT) and protease (P) genes were
      analyzed for drug resistance, using an in-house method carried out on 36 paired
      samples of plasma and PBMCs from 12 treatment-experienced patients in order to
      investigate resistance in the two compartments. When viruses in plasma and PBMCs
      were analyzed by patient, the mean of the Cohen kappa values was 0.728
      (substantial agreement). When viruses were analyzed by codon the mean of the
      Cohen kappa values was 0.715 (substantial agreement). Baseline samples were
      concordant at 280 of 288 (97%) codons analyzed. This study shows that a minority
      of mutations associated with previous therapy can be detected in PBMCs and not in
      plasma. Overall, mutations in plasma and PBMCs showed a substantial correlation
      in extensively treated patients, suggesting that either compartment is suitable
      for the detection of mutations as a virological guide for clinical care.

PMID- 10933617
TI  - Virologic and CD4+ cell responses to new nucleoside regimens: switching to
      stavudine or adding lamivudine after prolonged zidovudine treatment of human
      immunodeficiency virus infection. ACTG 302 Study Team. AIDS Clinical Trials
      Group.
AB  - Clinical benefit of zidovudine alone in the treatment of HIV infection wanes
      after several years, with decreasing CD4+ cell numbers and increasing HIV RNA in
      plasma. To develop treatment strategies following prolonged zidovudine treatment,
      92 subjects from the AIDS Clinical Trials Group (ACTG) 175 study after a median
      of 3.6 years of zidovudine monotherapy were randomized to treatment with
      stavudine or zidovudine and lamivudine. Evaluation of long-term changes, the
      average of 40- and 48-week HIV plasma RNA, demonstrated that lamivudine and
      zidovudine provided significantly greater virologic suppression compared with
      stavudine (mean decrease 0.70 versus 0.18 1og10 copies/ml,p = 0.003). Twenty-nine
      percent of zidovudine plus lamivudine recipients had HIV RNA levels below 500
      copies per milliliter at 48 weeks as compared with 4% of stavudine recipients (p
      = 0.02). Both regimens significantly increased CD4+ cell numbers, the means of
      weeks 40 and 48 rose to 49 and 36 CD4+ cells per cubic millimeter among
      zidovudine plus lamivudine and stavudine recipients, respectively. Treatments
      were well tolerated and only 3 of 92 subjects died or developed AIDS within 48
      weeks. In zidovudine-experienced subjects, addition of lamivudine resulted in
      significantly decreased plasma HIV RNA levels at 48 weeks compared with treatment
      with stavudine alone.

PMID- 10933618
TI  - Causal relationships between HIV-1 coreceptor utilization, tropism, and
      pathogenesis in human thymus.
AB  - The pathogenic differences between CXCR4 (X4)- and CCR5 (R5)-utilizing strains of
      HIV-1 may be predominantly due to differences in viral tropism, which in turn may
      be due to differential coreceptor utilization. We tested this hypothesis in the
      human thymus organ of the SCID-hu Thy/Liv mouse, using recombinants of NL4-3 that
      were isogenic except for Env coreceptor-binding determinants of the V1-V3 loops.
      Conversion of NL4-3 from an X4 to an R5 isolate was associated with altered
      tropism for cell subpopulations within the Thy/Liv organ (with a higher frequency
      of infection of thymic stromal cells, including macrophages), a slower rate of
      replication, and a lower level of cytopathicity. These observations underscore
      the causal relationships between tropism, coreceptor use, and cytopathicity in
      the human thymus in vivo.

PMID- 10933619
TI  - An AB recombinant and its parental HIV type 1 strains in the area of the former
      Soviet Union: low requirements for sequence identity in recombination. UNAIDS
      Virus Isolation Network.
AB  - In the former Soviet Union (SU) increasing numbers of HIV-1 infections among
      injecting drug users (IDU) have been reported, especially in the Ukraine. The
      main subtype transmitted among the IDUs seems to be subtype A, but limited
      numbers of subtype B cases have also been reported. In Kaliningrad, Russia, an AB
      recombinant strain was earlier shown to be responsible for the local outbreak.
      Here we describe the genetic relationship of HIV-1 strains circulating among IDUs
      in the former SU. For subtype A and the AB recombinant strains nearly full-length
      genomes were sequenced, and for one subtype B strain the entire envelope gene was
      cloned. The relationship between the AB recombinant strain and the subtype A and
      subtype B strains and the mosaic structure of the recombinant was studied by
      phylogenetic analysis. Ukrainian A and B strains were shown to be the probable
      parental viruses of the Kaliningrad AB recombinant strain. In the envelope gene
      the recombination breakpoint could also be precisely mapped to a region of
      similarity of only 14 base pairs. This suggests that only short stretches of
      absolute sequence identity may be needed for efficient RNA recombination between
      HIV-1 subtypes.

PMID- 10933620
TI  - The immunodeficiency virus coreceptor, Bonzo/STRL33/TYMSTR, is expressed by
      macaque and human skin- and blood-derived dendritic cells.
AB  - Dendritic cells (DCs) have been shown to be important in the replication of human
      and simian immunodeficiency viruses (HIV and SIV, respectively) in vivo and in
      vitro. DCs express CD4 and several chemokine receptors, such as CCR5 and CXCR4,
      which are important for viral entry. In vivo, DCs are abundant at body surfaces,
      where they might be one of the first cells that encounter naturally transmitted
      virus. Furthermore, DCs pulsed with HIV or SIV in vitro can efficiently transmit
      virus to T cells, thereby propagating vigorous viral replication. Reports have
      implicated Bonzo/STRL33/TYMSTR to be an additional alternative coreceptor for HIV
      and especially SIV infection. However, at present there are no reports regarding
      the expression of Bonzo/STRL33/TYMSTR by human or macaque DCs. Here we
      demonstrate the presence of Bonzo/STRL33/TYMSTR transcripts in rhesus macaque and
      human skin-derived DCs, in immature and mature blood monocyte-derived DCs, and in
      T cells from both skin and blood. Therefore, Bonzo/STRL33/TYMSTR is expressed in
      DCs and T cells that can play a role in the transmission of immunodeficiency
      viruses.

PMID- 10933621
TI  - A comparative study of the impact of HIV infection on natural killer cell number
      and function in Thais and North Americans.
AB  - Innate immunity may play a role in preventing HIV infection and progression to
      AIDS. Most studies of natural killer (NK) cell function have been conducted in
      populations with different HLA allele frequencies and HIV subtypes than those
      found in Southeast Asia. NK cell number and function, defined as CD3- cells
      expressing CD16+/CD56+ and the ability to lyse K562 cells, were enumerated in 42
      HIV-seronegative Thais and 20 HIV-seronegative North Americans. The number and
      percentage of NK cells were similar for both groups, but cytotoxicity function
      expressed as lytic units (LU20) of NK cells was significantly greater in the Thai
      subjects compared with the North American subjects (p = 0.004). Comparisons were
      also conducted between the HIV-seronegative groups and HIV-infected subjects from
      both Thailand and North America. NK cell number and function were not
      significantly different between the Thai HIV-seronegative and -seropositive
      groups. However, the comparison between the North American HIV-seronegative and 
      seropositive subjects demonstrated profound impairment of NK cell number,
      percentage, and function (p < 0.001). Matching the Thai and North American HIV
      infected subjects on CD4+ cell count revealed higher NK number and function in
      the Thai subjects (p < 0.001). The study indicates that NK function in both HIV
      seronegative and -seropositive Thais is elevated relative to similar groups in
      North America.

PMID- 10933622
TI  - Inhibition of natural killer cell cytotoxicity and interferon gamma production by
      the envelope protein of HIV and prevention by vasoactive intestinal peptide.
AB  - Natural killer (NK) cell dysfunction is common in human immunodeficiency virus
      (HIV)-infected subjects, although its mechanisms are poorly understood. A direct
      effect of HIV envelope glycoprotein gp120 may be involved. We investigated the in
      vitro effects of gp120 on the major NK cell effector functions, natural
      cytotoxicity and cytokine production. In addition, the ability of the vasoactive
      intestinal peptide (VIP) to modulate these effects was investigated. Our results
      indicated that gp120 inhibits NK natural cytotoxicity and showed, for the first
      time, that the inhibition affects also the production of the proinflammatory
      cytokine interferon-gamma (IFN-gamma). Interestingly, the inhibitory effect on NK
      cell functions was obtained with gp120 at concentrations within the range
      measured in the serum of HIV-infected subjects. Furthermore, we showed that the
      inhibitory activity of gp120 can be prevented by coincubation with VIP, even if
      VIP has no stimulatory activity by itself. Taken together these data suggest that
      (1) an inhibitory effect of gp120 may account for the NK cell dysfunction in HIV
      infected subjects; (2) the gp120-mediated decrease in IFN-gamma production by NK
      cells may contribute to the cytokine imbalance observed in HIV infection; and (3)
      VIP counteracts the inhibitory effect of gp120 on NK cell functions.

PMID- 10933623
TI  - Phylogenetic analysis of protease and transmembrane region of HIV type 1 group O.
AB  - The molecular diversity and phylogenetic relationship of 22 HIV-1 group O strains
      were examined on the basis of the protease gene and the N-terminal region of
      gp41env. Analysis of the newly characterized protease sequences with 12 reference
      sequences revealed no specific clustering patterns, despite the distinct
      geographic locations of the specimens. In contrast, analysis of the newly
      sequenced gp41 sequences with 34 published sequences revealed two distinct
      clusters, each represented by one full-length sequence (MVP5180 and ANT-70).
      Further, four of the specimens classified as group O in the protease region
      clustered with group M in the gp41 region (three subtype A and one subtype G,
      respectively), suggesting dual and/or recombinant infections with HIV-1 groups M
      and O. The presence of two distinct clusters in the gp41 region indicates at
      least two possible subtypes within group O viruses, and this may provide useful
      information regarding molecular epidemiological studies of group O infections.

PMID- 10933624
TI  - Introduction of HIV type 1 subtype E virus into South Korea.
AB  - Subtype E HIV-1 is the most prevalent strain in Southeast Asia. Although subtype
      B is prevalent in Korea, geographical distance and increases in travel may lead
      to the spread of subtype E in Korea. Therefore, we tried to identify and monitor
      the patterns of HIV subtype E virus introduction into Korea. The divergence of
      nucleotide sequences within the envelope region (V3 to V5) of Korean subtype E
      isolates ranged from 4.3 to 14.6% (n = 8; mean, 9.5 +/- 2.8%). In pairwise
      comparisons of subtype E isolates between Korea and other regions, the divergence
      of nucleotide sequences between 8 Korean and 16 Asian subtype E variants ranged
      from 1.3 to 15.2% (mean, 7.8 +/- 2.6%), whereas the divergence of nucleotide
      sequences between 8 Korean and 2 African variants ranged from 11.7 to 20.7%
      (mean, 15.4 +/- 2.2%). A phylogenetic tree showed that Korean subtype E isolates
      cluster with the Asian isolates but far from the African isolates. These
      epidemiological and molecular epidemiological data suggest that HIV-1 subtype E
      strains have been transmitted into Korea from endemic areas of Southeast Asia
      rather from Africa.

PMID- 10933625
TI  - Comparison of Vpu sequences from diverse geographical isolates of HIV type 1
      identifies the presence of highly variable domains, additional invariant amino
      acids, and a signature sequence motif common to subtype C isolates.
AB  - We compared the Vpu sequences from 101 strains of HIV-1 isolated from diverse
      geographical regions and various subtypes in order to identify regions of high
      variability, and those amino acid residues that were highly conserved or
      invariant. In addition to the highly conserved casein kinase II (CKII)
      phosphorylation sites, our analysis identified additional invariant residues in
      the transmembrane domain and in the first and second alpha-helical domains. Our
      analysis revealed that all subtype C sequences had a conserved LRLL motif at the
      C terminus that was also found in A/C intersubtype recombinants. While our
      analysis demonstrated the conservation of CKII domains in HIV-1 group M and O
      isolates, the number of potential CKII phosphorylation sites was variable in
      SIVcpz sequences. The results of this study will provide a basis for future
      mutagenesis studies to examine the role of certain amino acid residues in the
      structure and function of Vpu.

PMID- 10933626
TI  - SDF-1 production by placental cells: a potential mechanism of inhibition of
      mother-to-fetus HIV transmission.

PMID- 10933627
TI  - Methods used to conduct the pan-European Union survey on consumer attitudes to
      physical activity, body weight and health.
AB  - OBJECTIVE: The purpose of conducting this survey was to identify data on consumer
      attitudes towards and beliefs about physical activity, body weight and health
      among the 15 countries of the EU. DESIGN: A cross-sectional study to get a
      picture of the attitudes to physical activity, body weight and health in the EU.
      For this, it was considered important that samples be nationally representative
      so that inferences drawn from the data could be applied to the population in each
      country as well as to the EU population as a whole. Using a non-probability
      sampling method employing quota controls (and the national weight) we obtained
      large sample sizes from each country which were nationally representative in
      terms of the variables age, sex and regional distribution. To ensure samples were
      truly nationally representative a national weight was used when analysing the
      data using the same characteristics as those used to define quotas. When
      examining pooled estimates for the total EU sample a population weight was
      applied. RESULTS: In total, 15,239 subjects aged 15 years and upwards in the EU
      completed the survey. This article gives details on the methods used in carrying
      out the survey from design of the questionnaire to sample selection,
      questionnaire administration and analysis of the data. The methods and their
      limitations are discussed.

PMID- 10933628
TI  - Regional, demographic and national influences on attitudes and beliefs with
      regard to physical activity, body weight and health in a nationally
      representative sample in the European Union.
AB  - INTRODUCTION: Although the benefits of physical activity regarding body-weight
      gain and health in general are now widely accepted, physical activity levels
      remain low among citizens in the western world. This could be attributed to
      certain attitudes and beliefs about physical activity. Identifying and
      understanding these parameters would be the first step in an attempt to increase
      the levels of physical activity in populations generally characterized as having
      a sedentary lifestyle. OBJECTIVE: The aim of the present study was to identify
      the attitudes and beliefs regarding physical activity, body weight and health in
      a nationally representative sample in the EU and in particular to explore the
      demographic and national (cultural) influences on attitudes towards physical
      activity. DESIGN: In each member state of the EU, approximately 1000 adults aged
      15 years and over, were selected to complete an interviewer-assisted face-to-face
      questionnaire. Overall, a sample of 15,239 individuals in the EU participated in
      the study. Subject selection was quota-controlled to ensure samples in each
      country were nationally representative. RESULTS: On a European level wide
      variations were observed regarding the levels, beliefs and attitudes towards
      physical activity. More positive beliefs were observed among Finns, while less
      positive beliefs were observed among southern Europeans. A similar pattern was
      observed for attitudes, with the Portuguese having the highest percentage feeling
      that they do not need to be more physically active than they already are.
      However, most southern Europeans felt that a campaign would encourage them to
      become more active than they already are. On a demographic level, the youngest,
      more educated and most physically active subjects had more positive attitudes and
      beliefs towards physical activity and the health benefits derived from it; while
      for the overweight, beliefs and attitudes toward physical activity were related
      primarily to the benefits related to weight control. CONCLUSIONS: Lower levels of
      physical activity, an unwillingness to become active among non-participants and
      confusion regarding the weight gain benefits and general health benefits of
      exercise were reported more frequently among southern Europeans and older and
      less educated subjects. The Finns scored highest in all these parameters,
      possibly due to the programmes implemented and the beliefs and behaviour changes
      observed in this country during the last few years. The actions taken in Finland
      and their benefits could be employed appropriately in the other European states.

PMID- 10933629
TI  - Relationship between attitudes to health, body weight and physical activity and
      level of physical activity in a nationally representative sample in the European
      Union.
AB  - OBJECTIVE: To explore the factors that influence attitudes and beliefs about the
      effects of body weight and physical activity on health. DESIGN: Cross-sectional
      survey using a face-to-face interview-assisted questionnaire. SETTING: The survey
      was conducted between March and April 1997 in the 15 member states of the EU.
      SUBJECTS: Approximately 1000 adults aged 15 years plus from each country were
      selected by quota-controlled sampling; the total sample was of 15,239 persons
      (7162 males and 8077 females). Data were weighted by population size for each
      country and by age, gender and regional distribution within countries. RESULTS:
      Overall 27% of men and 35% of women reported not engaging in any form of
      recreational activity; rates were highest in those with a primary-level education
      (37% men, 43% women) compared with tertiary-level education (20% men, 25% women).
      Recreational activity levels declined with age and tended to be lowest in those
      who were more physically active at work. Eighteen per cent of respondents
      believed that physical activity was one of the two greatest influences on health;
      13% mentioned body weight, 38% mentioned food, 41% mentioned smoking and 33%
      mentioned stress. Logistic regression was used to assess for the effects of
      gender, age, educational level, body mass index (BMI), smoking status, activity
      level and country on beliefs that body weight and physical activity influenced
      health. Primary-educated, overweight, ex- and non-smoking women were most likely
      to mention body weight as an influence; young tertiary-educated, thinner, non
      smoking and active males were most likely to mention physical activity. There was
      wide variation across Europe in reported behaviour and beliefs, which persisted
      after taking account of all of the other factors in the regression model.
      CONCLUSIONS: Relatively few people in some countries believed body weight and
      physical activity were important influences on health. Many people mentioned
      stress and it might be possible to use this interest to motivate changes in
      physical activity to relieve stress. It may be important to take a more
      integrated approach to activity patterns that consider the role of work and
      recreation. Although social and demographic factors were important, after
      adjusting for these factors there was still wide between-country variation in
      reported attitudes, beliefs and behaviour. This will need to be taken into
      account in any activity promotion campaigns.

PMID- 10933630
TI  - Physical activity levels and body weight in a nationally representative sample in
      the European Union.
AB  - OBJECTIVES: The main objectives of this pan-European study were: (1) to identify
      different types of physical activity and the time devoted to them, (2) to assess
      physical activity/inactivity at work and in leisure time, and (3) to determine
      self-reported body weight and height. DESIGN AND SUBJECTS: In each member state
      of the EU, approximately 1000 adults, aged 15 years or more, were selected to
      participate in an interview-assisted face-to-face questionnaire on physical
      activity and body weight. In each country, sample selection was quota-controlled
      to ensure national representativeness. Overall, 15,239 subjects in the EU
      completed the study. RESULTS: On average in the EU, nearly three-quarters of the
      population participate in some kind of activity. In general, the highest
      proportions of participants were found in the Nordic countries and the lowest in
      the southern ones. At the European level, the five most common activities include
      walking, gardening, cycling, keep fit and swimming. Higher participation rates
      were found among men, younger subjects and those with a higher level of
      education. The majority of Europeans fall within the normal body mass index (BMI)
      range but more than one-third are overweight (31%) or obese (10%) and 11% have a
      BMI below 20. CONCLUSIONS: Several risk groups related to physical activity
      emerge from this survey: women, those with a lower level of education, older
      subjects, the overweight/obese and the underweight. Programmes to promote
      physical activity need to be tailored to the different groups identified in each
      country/region in order to increase adherence of non-participants and for the
      maintenance of those already engaged in activities.

PMID- 10933631
TI  - Stages of change towards physical activity in a nationally representative sample
      in the European Union.
AB  - OBJECTIVE: To examine the distribution of the stages of change towards physical
      activity across Europe and the influence of sociodemographic variables on this
      distribution. DESIGN: A cross-sectional study in which quota-controlled,
      nationally representative samples of approximately 1000 adults from each country
      completed a face-to-face interview-assisted questionnaire. SETTING: The survey
      was conducted in the 15 member states of the European Union between March and
      April 1997. SUBJECTS: The questionnaire was completed by 15,239 subjects (aged 15
      years upwards). Data were weighted by population size for each country and by
      sex, age and regional distribution within each member state. RESULTS: Twenty-nine
      per cent of subjects were in the precontemplation stage, while a similar
      proportion (30%) were in the maintenance stage. Ten per cent had been physically
      active but had relapsed recently. Considerable intercountry variation existed
      with Scandinavian countries tending to be lower in the precontemplation stage and
      southern countries tending to be higher (particularly Greece and Portugal). Men
      and younger subjects with a higher education level were more likely to be in the
      maintenance stage. Overweight and obese subjects were more likely to be in the
      precontemplation stage than normal-weight subjects. In terms of barriers to
      participating in physical activity 'not being the sporty type' was more important
      for those in precontemplation stages, while 'work/study commitments' was more
      important for those people in the maintenance stage. CONCLUSIONS: The model of
      the stages of behavioural change towards physical activity was able to
      distinguish people according to their level and attitude to physical activity.
      The considerable intercountry and sociodemographic variation in the distribution
      of stages of change suggest that targeted programmes aimed at specific subgroups
      in the population identified using the model may be more effective in promoting
      physical activity.

PMID- 10933632
TI  - Variables independently associated with self-reported obesity in the European
      Union.
AB  - OBJECTIVE: The rapid increase in obesity rates over recent years suggest that
      cultural and societal influences are affecting the adjustment in the energy
      balance equation in addition to other physiopathological or genetic determinants.
      Therefore, a pan-EU study was carried out to explore the influence of
      sociodemographic factors as well as some attitudes (smoking and exercise) on the
      prevalence of obesity in the adult population of all 15 member states of the EU.
      DESIGN: Overall, a sample of 15,239 individuals aged 15 years and upwards in the
      EU completed the questionnaire. Subject selection was quota-controlled to make
      the sample nationally representative following a multistage stratified cluster
      sampling. Self-reported height and weight were used to calculate body mass index
      (BMI). RESULTS: From the EU average results, it can be seen that only about half
      of the EU population (48%) is within the normal weight range, while the obesity
      (BMI > or = 30 kg m(-2)) prevalence was about 10% in the EU and the overweight
      prevalence was 36.6% and 25.6% among men and women, respectively. UK subjects had
      the highest prevalence of obesity (12%), while Italians, French and Swedes had
      the lowest levels of obesity (about 7%). Concerning age and social class
      interactions, logistic regression analysis showed that high social class and
      younger individuals in all groups had a lower odds ratio for obesity prevalence.
      People with a higher level of education are less likely to be obese, while the
      interaction between educational levels and obesity was different for men and
      women. A low participation in various leisure-time physical activities, the lack
      of interest (precontemplation) in being involved in exercise/physical activity
      and the increasing number of hours sitting down at work appear to be predictors
      of obesity. Single individuals were less prone to become obese than couples or
      widowed/divorced people. Finally, smoking status was statistically linked to the
      prevalence of obesity, since non-smokers or ex-smokers for more than 1 year
      presented a higher tendency for a BMI > 30. CONCLUSIONS: This survey confirms
      that a priority area for health intervention aimed at preventing the development
      of obesity should be to increase levels of physical activity, although the
      approach will depend on the population, especially with respect to educational
      and socioeconomic aspects.

PMID- 10933633
TI  - Recent body-weight changes and weight loss practices in the European Union.
AB  - OBJECTIVES: The aim of this paper is to describe recent weight changes and weight
      loss practices in the EU, and in particular to describe the group of subjects who
      were in a recent state of weight gain. DESIGN AND SUBJECTS: Overall, 15,239
      adults aged 15 years and upwards composed of 1000 from each EU member state were
      selected to complete the interview-assisted face-to-face questionnaire. In each
      member state, sample selection was quota-controlled to ensure national
      representativeness. RESULTS: This survey points to a fairly alarming tendency of
      more normal weight, overweight or obese European people being in a state of
      weight gain rather than weight loss. But it is also worrying that almost a fifth
      of underweight people are in the process of losing more weight. The
      recommendations for interventions to promote weight loss might be somewhat
      different between countries in the EU as the common weight loss practices differ
      between such countries. Overall, a campaign alone may not be effective in
      encouraging people to do more physical activity in Europe. Additional methods
      should be found. Furthermore, a combination of diet and exercise as a method of
      weight control is underestimated or undervalued by the general population who are
      either overweight or obese.

PMID- 10933634
TI  - Body image perception in relation to recent weight changes and strategies for
      weight loss in a nationally representative sample in the European Union.
AB  - OBJECTIVES: To assess body image perception and satisfaction with current body
      image across the EU and to explore the influence of sociodemographic variables,
      body-weight change and strategies for losing weight on body image perception.
      DESIGN: A cross-sectional study in which quota-controlled, nationally
      representative samples of approximately 1000 adults from each country completed a
      face-to-face interview-assisted questionnaire. SETTING: The survey was conducted
      in the 15 member states of the EU between March and April 1997. SUBJECTS: The
      questionnaire was completed by 15,239 subjects (aged 15 years and upwards). Data
      were weighted by population size for each country and by sex, age and regional
      distribution within each member state. RESULTS: Just 39% of respondents in the EU
      were satisfied with their weight and these were more likely to be male (46%)
      rather than female (31%). Across the EU 29% of Finnish subjects were content with
      their weight compared with 47% in Belgium and 48% in Luxembourg. The highest
      percentage of subjects who were content with their body weight was among females
      who were underweight (58%) and males who were normal weight (66%). A further 20%
      of underweight females wished to be lighter compared to only 5% of males. Diet
      was the most frequently selected method for losing weight especially among
      females wishing to be considerably lighter (27%) while males were as likely to
      use exercise as diet as a strategy to lose weight. CONCLUSIONS: Geographical and
      sociodemographical influences on body image perception are evident across the EU.
      There were clear gender differences in the desire to be thinner with a high
      proportion of females who were underweight being content to be so.

PMID- 10933636
TI  - Chronic prostatitis-an infectious disease?

PMID- 10933635
TI  - Perceived benefits and barriers to physical activity in a nationally
      representative sample in the European Union.
AB  - OBJECTIVE: To examine the attitudes of consumers, in particular their perceived
      benefits and barriers to physical activity from all EU member states, and having
      a measure of prevailing levels of activity, inactivity and self-reported body
      weight and body shape. DESIGN: Cross-sectional survey using an interview-assisted
      face-to-face questionnaire. SETTING: The survey was conducted between March and
      April 1997 in the 15 member states of the EU. SUBJECTS: Overall, 15,239 EU
      subjects, classified according to sex, age (six levels) and highest level of
      education attained (primary, secondary or tertiary), completed the survey. Sample
      selection of subjects in each EU member state was quota-controlled to ensure they
      were nationally representative. RESULTS: The most important motivation for people
      to participate in physical activity is to maintain good health (42%), to release
      tension (30%) and to get fit (30%). The importance of the health argument is
      highest in older persons and in subjects with a primary education level. Only 13%
      of the EU population (16% of women, 10% of men) perceived losing weight as a
      benefit of physical exercise. The most important barriers to increase physical
      activity are work or study commitments (28%) and the subjects' belief that they
      are not 'the sporty type' (25%). There is considerable between-country variation
      in the answering pattern within the EU.

PMID- 10933637
TI  - The use of in vitro pharmacodynamic models of infection to optimize
      fluoroquinolone dosing regimens.

PMID- 10933638
TI  - Flucytosine: a review of its pharmacology, clinical indications,
      pharmacokinetics, toxicity and drug interactions.
AB  - Flucytosine (5-FC) is a synthetic antimycotic compound, first synthesized in
      1957. It has no intrinsic antifungal capacity, but after it has been taken up by
      susceptible fungal cells, it is converted into 5-fluorouracil (5-FU), which is
      further converted to metabolites that inhibit fungal RNA and DNA synthesis.
      Monotherapy with 5-FC is limited because of the frequent development of
      resistance. In combination with amphotericin B, 5-FC can be used to treat severe
      systemic mycoses, such as cryptococcosis, candidosis, chromoblastomycosis and
      aspergillosis. Recently, 5-FC has been combined with newer azole antifungal
      agents; it also plays an important role in a new approach to the treatment of
      cancer. The severe side effects of 5-FC include hepatotoxicity and bone-marrow
      depression. In most patients, these side effects are concentration dependent,
      predictable, possibly avoidable with close monitoring to maintain 5-FC
      concentrations at <100 mg/L, and reversible with drug discontinuation or
      reduction of dose. 5-FC is well absorbed after oral administration, penetrates
      into body tissues well and is excreted mainly by the kidneys. In renal failure,
      major dose adjustments have to be made. The most important drug interaction of 5
      FC occurs with concomitant administration of 5-FC and nephrotoxic drugs,
      especially amphotericin B. Owing to the crucial role of glomerular filtration in
      5-FC elimination, drugs that impair this mechanism will decrease the elimination
      of 5-FC and thus prolong its half-life.

PMID- 10933639
TI  - Evaluation of (1R,2R)-1-(5'-methylfur-3'-yl)propane-1,2,3-triol, a sphydrofuran
      derivative isolated from a Streptomyces species, as an anti-herpesvirus drug.
AB  - (1R,2R)-1-(5'-Methylfur-3'-yl)propane-1,2,3-triol (MFPT), a stable anhydro
      derivative of sphydrofuran, was obtained from the culture broth of STREPTOMYCES:
      sp. strain FV60 as an inhibitor of herpes simplex virus type 1 (HSV-1). The
      compound showed antiherpetic activity with a 50% inhibitory concentration of 1.2
      IM in an in vitro assay system. Although the binding of virus to host cells was
      not inhibited, the penetration of virus into cells was moderately blocked by
      MFPT. Some of the viruses, once they had penetrated cells, failed to form plaques
      in the presence of MFPT. When added to the late stages of HSV-1 replication, MFPT
      also inhibited virus production. Sodium dodecyl sulphate-polyacrylamide gel
      electrophoresis analysis of isotope-labelled HSV-specific proteins revealed that
      a protein or proteins with reduced molecular weight (about 120 kDa) was clearly
      detected in cells treated with MFPT. Western blot analysis with antibodies
      against three HSV-specific glycoproteins (gB, gC and gD) showed a significant
      difference in gC synthesis between untreated and MFPT-treated cells. Release of
      progeny viruses was suppressed by MFPT. Syncytium formation by HSV-1 strain HF
      was inhibited and small plaques with rounded cells were formed in MFPT-treated
      cell cultures. When wild-type HSV-1 was serially propagated under the selective
      pressure of MFPT, resistant virus emerged. MFPT-resistant progeny were
      accompanied by the formation of plaques with rounded cells. These results, taken
      together, suggest that MFPT might act by limiting the maturation of HSV-specific
      glycoproteins, particularly of HSV-1 gC.

PMID- 10933640
TI  - Modulation of fluconazole sensitivity by the interaction of mitochondria and
      erg3p in Saccharomyces cerevisiae.
AB  - We studied the effects of fluconazole, an ergosterol-depleting agent, in
      Saccharomyces cerevisiae, a genetically tractable fungus closely related to
      Candida albicans. The wild-type Saccharomyces strain was sensitive to
      fluconazole, but the isogenic cytoplasmic petite mutant (rho-) was resistant. The
      mechanism of resistance of rho- mutants appeared to involve uncoupling of
      oxidative phosphorylation. However, the petite strain with a mutation in cent5, 6
      desaturase (erg3 rho-) was sensitive to fluconazole, in contrast to its erg3 rho+
      counterpart. It is known that erg3 mutants are azole resistant through the
      accumulation of 14-methyl-fecosterol, a less toxic ergosterol intermediate. These
      results indicate that mitochondria function as important physiological partners
      with Erg3p in the accumulation of toxic sterol intermediates in the presence of
      azoles.

PMID- 10933641
TI  - Efflux-mediated resistance to fluconazole could be modulated by sterol
      homeostasis in Saccharomyces cerevisiae.
AB  - Saccharomyces cerevisiae has long been used as a model organism in the study of
      the ergosterol pathway and its inhibitors. The Pdr5 protein (Pdr5p), an ATP
      binding cassette transporter, plays an important role in active efflux of azole
      antifungals and therefore in azole sensitivity and resistance in S. cerevisiae.
      We have identified the Fluconazole Dominant Resistance-1 (FDR-1) mutant, which
      has a single dominant mutation conferring high-level resistance to fluconazole.
      FDR-1 has been found to be an activated allele of the Pleiotropic Drug Resistance
      1 (PDR-1) gene (termed PDR1-100) and to upregulate PDR5 transcription. Resistance
      of PDR1-100 to fluconazole decreased in the background of mutations known to
      affect sterol homeostasis. Hence, the resistance to fluconazole of PDR1-100 was
      paradoxically decreased in an erg3 PDR1-100 double mutant. The erg3 mutants are
      resistant to azoles and accumulate 14-methyl-fecosterol instead of ergosterol in
      the presence of azoles. These results reinforce the emerging evidence in both S.
      cerevisiae and Candida albicans that sterols could serve as substrates for Pdr5p
      for transport across membranes.

PMID- 10933642
TI  - Antibiotic resistance patterns of aerobic coryneforms and furazolidone-resistant
      Gram-positive cocci from the skin surface of the human axilla and fourth toe
      cleft.
AB  - Samples of skin surface bacteria from 28 healthy subjects plated directly on to
      selective and non-selective media revealed that the proportion of aerobic
      coryneforms and furazolidone-resistant Gram-positive cocci (FURECs) resistant to
      erythromycin was significantly greater in the fourth toe cleft than in the axilla
      (P < 0.05). There were more erythromycin-resistant bacteria than tetracycline
      resistant bacteria at both sites (P = 0.001 for the toe cleft; P < 0.01 for the
      axilla). In total, 160 distinct isolates were obtained, of which 42 were FURECs
      and 118 were aerobic coryneforms. Of these, 153 (96%) were resistant to
      erythromycin and 66 (41%) to tetracycline. All except seven of the tetracycline
      resistant strains were also resistant to erythromycin. The resistant isolates
      belonged to a variety of species. CDC group ANF corynebacteria were most numerous
      and composed 31% of all isolates. The majority (76%) of FURECs were identified as
      Micrococcus luteus. MIC determinations on selected strains revealed that
      tetracycline-resistant FURECs were sensitive to doxycycline and minocycline, as
      were most tetracycline-resistant coryneforms. Nine coryneform isolates were cross
      resistant to all three tetracyclines. Only a minority of erythromycin-resistant
      FURECs (21%) demonstrated a macrolide-lincosamide-streptogramin type B (MLS)
      resistant phenotype with inducible or constitutive cross-resistance to
      clindamycin and the type B streptogramin, pristinamycin IA. Twenty-nine
      erythromycin-resistant FURECs had a novel phenotype distinct from MLS and
      macrolide-streptogramin type B resistance. In contrast, most coryneforms (79%)
      were MLS resistant. Among the remainder, two unusual erythromycin resistance
      phenotypes were apparent, both of which differed from the unusual phenotype in
      FURECs. This study has revealed that the non-staphylococcal aerobic flora of skin
      contains a considerable reservoir of tetracycline and erythromycin resistance
      determinants. The three unusual macrolide resistance phenotypes may be associated
      with novel resistance mechanisms.

PMID- 10933643
TI  - Cross-resistance patterns among clinical isolates of Klebsiella pneumoniae with
      decreased susceptibility to cefuroxime.
AB  - The frequency of decreased susceptibility to cefuroxime and quinolones and the
      correlation between these drug resistance traits was investigated in clinical
      isolates of Klebsiella pneumoniae from two Danish counties. Eighty-three randomly
      selected clinical isolates of K. pneumoniae with decreased susceptibility to
      cefuroxime were examined for cross-resistance patterns and the production of beta
      lactamases. The frequency of resistance to cefuroxime and ciprofloxacin has
      increased from <5% in 1990 to 15% and 7% in 1998, respectively. Two of the 83
      isolates were multiply resistant and seemed to produce extended-spectrum beta
      lactamases. However, cross-resistance to ciprofloxacin and other classes of drug
      in 68% of the remaining isolates indicates that other resistance mechanisms, such
      as penetration barriers, had probably been selected in these Danish isolates. The
      susceptibility to ciprofloxacin decreased successively with decreasing
      susceptibility to cefuroxime for K. pneumoniae. This did not occur in cefuroxime
      resistant Escherichia coli.

PMID- 10933644
TI  - Increasing resistance to fluoroquinolones in escherichia coli from urinary tract
      infections in the netherlands.
AB  - In continuous surveillance of routine samples from five Dutch laboratories, we
      studied resistance to the antibiotics most commonly prescribed for urinary tract
      infections (UTI) in The Netherlands, namely norfloxacin, amoxycillin,
      trimethoprim and nitrofurantoin, from 1989 to 1998 in >90000 Escherichia coli
      isolates. Resistance to norfloxacin increased from 1.3% in 1989 to 5.8% in 1998.
      Multiresistance, defined as resistance to norfloxacin and at least two of the
      other three antibiotics, increased from 0.5% in 1989 to 4. 0% in 1998.
      Multivariate analysis of the norfloxacin resistance demonstrated that this yearly
      increase (the odds ratio was 1.0 in 1989, 1.6 in 1992, 2.9 in 1995 and 6.1 in
      1998) was independent of other determinants of resistance to norfloxacin, such as
      age, gender and origin of the isolate. Analysis of strata, classified by year,
      age and gender, demonstrated an association between prescription of
      fluoroquinolones (defined daily doses per case of UTI) and resistance to
      norfloxacin in E. coli (P < 0.001). There was no significant association with the
      prescription of nitrofuran derivatives (nitrofurantoin) and trimethoprim with or
      without sulphamethoxazole. The yearly increase of resistance to fluoroquinolones
      in E. coli from UTI may stem from increased prescription of fluoroquinolones for
      UTI. Resistance of E. coli to these agents is likely to increase further as
      fluoroquinolone use increases in future.

PMID- 10933645
TI  - A comparative study of the in vitro susceptibilities of clinical and laboratory
      selected resistant isolates of Aspergillus spp. to amphotericin B, itraconazole,
      voriconazole and posaconazole (SCH 56592).
AB  - We investigated the in vitro susceptibilities of clinical and laboratory-selected
      Aspergillus spp. to posaconazole, and compared the results with those obtained
      for amphotericin B, itraconazole and voriconazole. Conidial suspensions from
      clinical isolates (284 Aspergillus fumigatus, 66 Aspergillus niger, 31
      Aspergillus flavus and 43 Aspergillus spp.) and laboratory-selected resistant A.
      fumigatus isolates (15 resistant to amphotericin B, 25 to itraconazole and 12 to
      voriconazole) were prepared and their susceptibilities to various antifungal
      agents determined using a previously described broth macrodilution technique. The
      geometric mean MICs (mg/L) of posaconazole for A. fumigatus (0.17 +/- 0.11) and
      non-A. fumigatus aspergilli (0.16 +/- 0.28) were significantly lower (P 0.05)
      than those for amphotericin B, itraconazole and voriconazole. Amphotericin B
      resistant A. fumigatus isolates were as susceptible to posaconazole as the
      parental strain. Itraconazole- and voriconazole-resistant isolates showed low
      level (two- to three-fold increase in MICs) cross-resistance to posaconazole. The
      minimum fungicidal concentrations (mg/L) of posaconazole for A. fumigatus (n =
      58) and non-A. fumigatus aspergilli (n = 40) were 4. 45 +/- 2.70 (range 0.25-8)
      and 4.14 +/- 3.03 (range 0.5-8), respectively. Time-kill studies showed that the
      fungicidal activity of posaconazole against A. fumigatus is time- and
      concentration-dependent (for example, posaconazole 4 mg/L killed >99% of A.
      fumigatus conidia within 24 h). These results suggest that overall, posaconazole
      has better activity and a smaller range of MICs for Aspergillus spp., including
      those with reduced susceptibility to amphotericin B, itraconazole and
      voriconazole.

PMID- 10933646
TI  - Intravenous infusion of erythromycin inhibits CXC chemokine production, but
      augments neutrophil degranulation in whole blood stimulated with Streptococcus
      pneumoniae.
AB  - Macrolides may influence the inflammatory response to an infection by mechanisms
      that are unrelated to their antimicrobial effect. Indeed, erythromycin and other
      macrolides inhibit cytokine production and induce degranulation of neutrophils in
      vitro. CXC chemokines are small chemotactic cytokines that specifically influence
      neutrophil functions. To determine the effect of a clinically relevant dose of
      erythromycin on the production of CXC chemokines and neutrophil degranulation,
      six healthy humans received a 30 min iv infusion of erythromycin (1000 mg). Whole
      blood obtained before and at various times after the infusion was stimulated ex
      vivo with heat-killed Streptococcus pneumoniae. Ex vivo production of the CXC
      chemokines interleukin 8 (IL-8) and epithelial cell-derived neutrophil attractant
      78 (ENA-78), in whole blood obtained after erythromycin infusion, was lower than
      that in blood drawn before erythromycin infusion (maximum inhibition post
      infusion: 32.9 +/- 6.5% and 35.2 +/- 12.6% decrease in production, respectively,
      expressed as percentage change relative to production before infusion of
      erythromycin, both P < 0.05). In contrast, infusion of erythromycin was
      associated with an enhanced capacity of whole blood to release the neutrophil
      degranulation products bactericidal/permeability increasing protein (BPI), human
      neutrophil elastase (HNE) and human lactoferrin (HLF) upon stimulation with S.
      pneumoniae. Effects of erythromycin were greatest 4 h after infusion was stopped,
      when BPI, HNE and HLF concentrations were increased by +107.6 +/- 33.5%, +134.7
      +/- 34.8% and +205.9 +/- 55.9 %, respectively (expressed as percentage change
      relative to production before infusion of erythromycin) (all P < 0. 05). These
      results indicate the ability of erythromycin to reduce CXC chemokine production
      and to enhance neutrophil degranulation in human blood.

PMID- 10933647
TI  - Influence of a new fluoroquinolone, AF3013 (the active metabolite of
      prulifloxacin), on macrophage functions against Klebsiella pneumoniae: an in
      vitro comparison with pefloxacin.
AB  - The efficacy of an antibiotic in the treatment of bacterial infections depends
      upon the interaction of bacterium, drug and phagocytes. In this study we have
      investigated the influence of AF3013, a new fluoroquinolone, on the activities of
      mouse peritoneal macrophages against Klebsiella pneumoniae, in comparison with
      the influence of pefloxacin. Bacterial susceptibility to phagocytosis and
      intracellular killing were determined after klebsiellae and macrophages had been
      incubated simultaneously with inhibitory concentrations of both AF3013 and
      pefloxacin and following pre-exposure of the microorganisms and the macrophages
      individually to the same concentrations of each drug. Under the experimental
      conditions used, both AF3013 and pefloxacin potentiated the phagocytic and
      microbicidal activities of the macrophages, although different mechanisms may be
      involved.

PMID- 10933648
TI  - Grepafloxacin against penicillin-resistant pneumococci in the rabbit meningitis
      model.
AB  - Grepafloxacin, a new fluoroquinolone, produced bactericidal activity comparable
      to that of vancomycin and ceftriaxone in the treatment in rabbits of meningitis
      caused by a pneumococcal strain highly resistant to penicillin (MIC 4 mg/L)
      (triangle uplog(10) cfu/mL*h for grepafloxacin, -0.32 +/- 0.15; dose, 15 mg/kg
      iv; triangle uplog(10) cfu/mL*h for vancomycin, -0.39 +/- 0.18; dose, 2 x 20
      mg/kg iv; triangle uplog(10) cfu/mL*h for ceftriaxone, -0.32 +/- 0. 12; dose, 125
      mg/kg iv). Higher doses of grepafloxacin (30 mg/kg and 2 x 50 mg/kg) did not
      improve the killing rates. The combination of grepafloxacin with vancomycin was
      not significantly superior to monotherapies (P > 0.05). In vitro, grepafloxacin
      was bactericidal at concentrations above the MIC. Using concentrations around the
      MIC, addition of vancomycin to grepafloxacin showed synergic activity.

PMID- 10933649
TI  - Comparative efficacy of 5 days of dirithromycin and 7 days of erythromycin in
      skin and soft tissue infections.
AB  - We investigated the comparative efficacy and safety of dirithromycin and
      erythromycin in the treatment of skin and soft tissue infections in this double
      blind, randomized, multicentre study, in which 439 patients were randomized to
      treatment with dirithromycin (500 mg daily for 5 days) or erythromycin (250 mg
      every 6 h for 7 days). All randomized patients were included in the termination
      analysis, which showed that 187 of 220 (85.0%) dirithromycin recipients and 177
      of 219 (80.8%) erythromycin recipients were clinically cured or improved (95%
      confidence interval (CI) -3.0% to +11.4%). In the termination analysis of the 211
      bacteriologically evaluable patients, clinical cure or improvement occurred in 83
      of 100 (83%) dirithromycin recipients and in 89 of 111 (80.2%) erythromycin
      recipients (95% CI -7.8% to +13.4%), and bacteriological eradication occurred in
      85 of 100 (85%) and 89 of 111 (80.2%), respectively. Adverse events were similar
      in incidence and nature between the two groups, except that there was less nausea
      with dirithromycin (3.6% versus 8.2%; P = 0.042). Ten of 220 (4.5%) dirithromycin
      recipients and 27 of 219 (12.3%) erythromycin recipients returned >20% of their
      prescribed medication (P = 0.033). In the treatment of skin and soft tissue
      infections, dirithromycin (500 mg daily for 5 days) was comparable in efficacy
      to, and caused significantly less nausea than, erythromycin (250 mg every 6 h for
      7 days). Compliance with the dirithromycin regimen was superior to that with the
      erythromycin regimen.

PMID- 10933650
TI  - Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating
      amphotericin B.
AB  - NS-718, a lipid nanosphere incorporating amphotericin B, is effective against
      pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with
      that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using
      renal cell cultures and in vivo by biochemical analysis, histopathological study
      of the kidney and pharmacokinetic study of amphotericin B following intravenous
      infusion of the formulation in rats. Incubation with NS-718 resulted in
      significantly less damage of cultured human renal proximal tubular epithelial
      cells compared with D-AmB. Serum blood urea and creatinine concentrations
      increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in
      those given the same dose of NS-718. Histopathological examination of the kidney
      showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated
      rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were
      higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest
      that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates
      the nephrotoxicity of amphotericin B.

PMID- 10933651
TI  - Investigation of the anti-inflammatory and membrane-stabilizing potential of
      spiramycin in vitro.
AB  - The effects of the 16-member macrolide spiramycin (2.5-80 mg/L) and the 14-member
      agent clarithromycin on the production of superoxide by activated human
      neutrophils were compared in vitro and related to membrane-stabilizing activity.
      Superoxide production was measured by lucigenin-enhanced chemiluminescence with N
      formyl-L-methionyl-L-leucyl-L-phenylalanine (1 microM) as the stimulus, and
      membrane-stabilizing activity was measured by a haemolytic procedure.
      Clarithromycin, but not spiramycin, caused dose-related inhibition of superoxide
      production by activated neutrophils and also protected erythrocytes against
      haemolysis, while spiramycin possessed only weak membrane-stabilizing activity.
      These observations underscore the apparent association between the anti
      inflammatory and membrane-stabilizing properties of macrolides.

PMID- 10933652
TI  - Relationship between outer membrane alterations and susceptibility to
      antimicrobial agents in isogenic strains of Klebsiella pneumoniae.
AB  - The activities of beta-lactams, chloramphenicol, tetracycline, fluoroquinolones
      and aminoglycosides against Klebsiella pneumoniae C3 (O1:K66, producing porins
      OmpK35 and OmpK36) and a set of isogenic mutants derived from it lacking the O
      antigen of lipopolysaccharide (LPS), capsular K antigen, or one or both porins
      were determined. MICs remained within one dilution step in mutants deficient in
      antigen O, in capsule or in one of the two porins. No increases in the MICs of
      aminoglycosides, fluoroquinolones, tetracycline and chloramphenicol were observed
      for strains deficient in the two porins, but the MICs of ampicillin, cephalothin,
      cefoxitin, cefotaxime and ceftazidime for this type of mutant increased four- to
      >256-fold. The highest MICs of beta-lactams were obtained in a porin-deficient
      mutant expressing increased beta-lactamase activity. It is concluded that
      isolated outer membrane alterations in K. pneumoniae are not decisive factors in
      increasing resistance to antimicrobial agents, but porin loss co-operates with
      beta-actamase production to increase resistance to beta-lactams.

PMID- 10933653
TI  - Salicylate induction of phenotypic resistance to quinolones in Serratia
      marcescens.
AB  - The influence of salicylic acid on the permeability and susceptibility of
      Serratia marcescens to both nalidixic acid and ciprofloxacin was studied, as well
      as the effect of salicylate on outer membrane proteins and lipopolysaccharide. As
      salicylic acid concentration increased, ciprofloxacin accumulation decreased with
      a concomitant, previously observed, reduction in the porin content of the outer
      membrane. Resistance to ciprofloxacin and nalidixic acid was enhanced when
      bacteria grew in the presence of salicylic acid.

PMID- 10933654
TI  - Susceptibility of Helicobacter pylori to mupirocin, oxazolidinones,
      quinupristin/dalfopristin and new quinolones.
AB  - The in vitro activities of mupirocin, quinupristin/dalfopristin, linezolid,
      eperezolid, sitafloxacin, clinafloxacin, moxifloxacin, amoxycillin, metronidazole
      and clarithromycin were tested at pH 7.4 against 57 strains of Helicobacter
      pylori. The most active agents (mupirocin, sitafloxacin and clinafloxacin) were
      also tested for activity at pH 5.4 against the same strains. Mupirocin was very
      active at pH 7.4 and 5.4 (MIC90 0.25 and 0.12 mg/L, respectively).
      Quinupristin/dalfopristin, linezolid and eperezolid had low activity (MIC90 4, 8
      and 4 mg/L, respectively). Sitafloxacin (MIC90 </= 0.008 mg/L) was the most
      active fluoroquinolone, while clinafloxacin (MIC90 0.12 mg/L) and moxifloxacin
      (MIC90 2 mg/L) were least active.

PMID- 10933655
TI  - In vitro antibiotic susceptibility of Francisella tularensis isolated from humans
      and animals.
AB  - The in vitro susceptibility of 38 strains of Francisella tularensis (biovar F.
      tularensis palaearctica) was determined using Etests on cysteine heart agar
      plates with 2% haemoglobin. All strains were susceptible to the antibiotics
      traditionally used to treat tularaemia, such as streptomycin (MIC(90) 4.0 mg/L),
      tetracycline (MIC(90) 0.38 mg/L) and chloramphenicol (MIC(90) 0.38 mg/L), and to
      aminoglycosides, such as tobramycin (MIC(90) 1.5 mg/L) and gentamicin (MIC(90)
      1.0 mg/L). The quinolones examined had low MIC(90)s: ciprofloxacin, 0.016 mg/L;
      levofloxacin, 0.016 mg/L; grepafloxacin, 0.047 mg/L; and trovafloxacin, 0.032
      mg/L. In contrast, all the strains were resistant to beta-lactams and
      azithromycin. Quinolones thus seem to be promising drugs for the treatment of
      tularaemia.

PMID- 10933656
TI  - Development of simultaneous resistance to fluconazole in Candida albicans and
      Candida dubliniensis in a patient with AIDS.
AB  - In this report, we describe a patient with recurrent episodes of oral candidosis
      who finally suffered from fluconazole-refractory oral and oesophageal candidosis.
      The patient was monitored for 4 years until his death from AIDS. During the
      observation period, persistent colonization with both Candida albicans and
      Candida dubliniensis was observed. From the appearance of the first episode of
      oral candidosis, the patient was treated with fluconazole for 18 months. The
      infection became unresponsive to fluconazole 400 mg/day. In vitro susceptibility
      testing revealed the development of resistance to fluconazole in C. albicans and
      C. dubliniensis. Molecular typing confirmed the persistence of the same C.
      albicans and C. dubliniensis strains which developed resistance after up to 3
      years of asymptomatic colonization. This observation demonstrates that Candida
      spp. other than C. albicans may develop resistance to fluconazole in a patient
      who is repeatedly exposed to the drug.

PMID- 10933657
TI  - Antimicrobial resistance of mesophilic Aeromonas spp. isolated from two European
      rivers.
AB  - The activity of 19 antibiotics and four antiseptics and/or disinfectants was
      studied against 138 non-redundant strains of Aeromonas spp. (104 Aeromonas
      caviae, 22 Aeromonas sobria and 12 Aeromonas hydrophila) isolated from two
      European rivers. Antibiotic resistance frequencies were: nalidixic acid, 59%;
      tetracycline, 14%; fosfomycin, 8%; tobramycin and cotrimoxazole, 7%; cefotaxime,
      4%; chloramphenicol, 2%; gentamicin, 1%. Most of the nalidixic acid-resistant
      strains were susceptible to fluoroquinolones (54-98%). Antibiotic resistance
      rates varied according to the source of the strains. All Aeromonas spp. strains
      were killed by 50 ppm of chlorine, cetylpyridinium chloride and peracetic acid,
      and by 1600 ppm of glutaraldehyde.

PMID- 10933658
TI  - Activity of antibiotics used in human medicine for Campylobacter jejuni isolated
      from farm animals and their environment in Lancashire, UK.
AB  - A retrospective study of 96 Campylobacter jejuni isolated from farm animals and
      the environment showed that most were less susceptible than the NCTC type strain
      to nalidixic acid (MICs 4-32 mg/L), ciprofloxacin (MICs 1-2 mg/L) and
      erythromycin (MICs 16-64 mg/L), but had similar susceptibility to tetracycline
      (MICs 4-8 mg/L) and kanamycin (MICs 4-8 mg/L). None had the high MICs of
      ciprofloxacin (>32 mg/L) or erythromycin (1024 mg/L) typically associated with
      clinical resistance in this species. Some farms used antimicrobial agents, but
      there was no obvious association between the use of agents and the susceptibility
      of the isolates.

PMID- 10933659
TI  - Community antibiotic therapy, hospitalization and subsequent respiratory tract
      isolation of Haemophilus influenzae resistant to amoxycillin: a nested case
      control study.
AB  - The study objective was to determine whether recent community antibiotic
      prescribing and hospitalization are associated with beta-lactam resistance in
      respiratory isolates of Haemophilus influenzae. Data obtained for hospitalization
      and community prescribing (in the previous 3 months) from 412 adults (>15 years)
      in whom an episode of respiratory tract infection had been described, during
      which H. influenzae was isolated, were analysed. Seventy-three (17.7%) isolates
      of H. influenzae were resistant to amoxycillin. Resistance was associated with
      recent hospitalization [odds ratio (OR) 3.2, 1.8-5.6] and antibiotic exposure in
      the community (2.1, 1.2-3.6). These variables were independently associated with
      amoxycillin resistance [hospitalization (OR 4.5, 1. 7-12.5) and community beta
      lactam antibiotic exposure (3.9, 1.6-9. 8)]. Hospitalized patients probably
      received antibiotics during their admission although aquisition of the organism
      or the beta-lactamase via plasmids from other Gram-negative organisms in the
      hospital could also be a factor. Control measures to reduce the inappropriate use
      of antimicrobials in the community and in hospital need to be reinforced.

PMID- 10933660
TI  - Treatment of experimental osteomyelitis caused by methicillin-resistant
      Staphylococcus aureus with a biodegradable system of lactic acid polymer
      releasing pefloxacin.
AB  - A novel biodegradable system of D-,L-dilactide delivering pefloxacin was
      implanted in 104 rabbits with experimental osteomyelitis caused by methicillin
      resistant Staphylococcus aureus (MRSA), 26 serving as controls. Animals were
      killed on each third day and viable bacterial counts and levels of pefloxacin in
      bone tissue were determined. A 99. 9% decrease in viable count of bacteria was
      achieved by day 12 and complete bacterial eradication on day 33. Pefloxacin was
      released gradually, reaching its peak on day 15 at levels 100 times the MIC of
      pefloxacin for MRSA. The biodegradable system described may have a future role in
      the therapeutic approach to osteomyelitis.

PMID- 10933661
TI  - Plasma, urine and skin pharmacokinetics of cefepime in burns patients.
AB  - We studied the pharmacokinetics of cefepime (2 g bd) in six burns patients.
      Blood, urine and skin samples were collected to measure cefepime concentrations.
      A two-compartment model was fitted to the data. At day 1, t(1/2beta) was 2.45 +/-
      0.56 h, V(ss) 0.36 +/- 0.1 L/kg, total clearance 152 +/- 25.2 mL/min, and AUC 217
      +/- 34 mg*h/L. There was no statistical difference between day 1 and day 3 for
      any of the pharmacokinetic parameters. We demonstrated good penetration of
      cefepime in skin. These results show that it is not necessary to change the
      standard dosage of cefepime in burns patients.

PMID- 10933662
TI  - Concentrations of single-dose meropenem (1 g iv) in bronchoalveolar lavage and
      epithelial lining fluid.
AB  - The concentrations of meropenem were measured in plasma, bronchoalveolar lavage
      (BAL) and epithelial lining fluid (ELF) 0.5-8 h after the administration of a
      single 1 g iv dose of meropenem. Thirty-five patients undergoing bronchoscopy
      were studied. Mean concentrations in plasma, BAL and ELF, respectively, measured
      by high performance liquid chromatography, were as follows: 0.5 h: 25. 96, 0.14,
      5.04 mg/L; 1 h: 14.98, 0.09, 7.07 mg/L; 2 h: 12.01, 0.06, 3.86 mg/L; 4 h: 2.51,
      0.04, 2.20 mg/L; 6 h: 0.57, 0, 0.59 mg/L; 8 h: 0.29, 0, 0 mg/L. Throughout the 2
      h following infusion, concentrations in ELF exceeded the MIC90 for all nosocomial
      and community-acquired respiratory pathogens, including Pseudomonas aeruginosa
      (3.05 mg/L), Haemophilus influenzae (0.16 mg/L) and penicillin-resistant
      Streptococcus pneumoniae (0.86 mg/L). These results support the clinical efficacy
      of meropenem in the treatment of a wide range of pulmonary infections.

PMID- 10933663
TI  - Reply

PMID- 10933664
TI  - Antiviral susceptibilities of herpes simplex virus from immunocompetent subjects
      with recurrent herpes labialie: a UK-based survey.

PMID- 10933665
TI  - PCR detection of the vanA gene in a vancomycin-resistant Enterococcus faecalis
      clinical isolate from Hungary.

PMID- 10933667
TI  - Assessment of the Etest method for detection of penicillin resistance in acute
      suppurative oral infection.

PMID- 10933668
TI  - Comparison of the MICs of cefepime for extended-spectrum beta-lactamase-producing
      and non-extended-spectrum beta-lactamase-producing strains of Enterobacter
      cloacae.

PMID- 10933666
TI  - Detection of extended-spectrum beta-lactamases with Etest and double-disc
      potentiation methods.

PMID- 10933669
TI  - In vitro antibacterial activities of telithromycin, a new ketolide, against
      bacteria causing infections in obstetric and gynaecological patients.

PMID- 10933670
TI  - In vitro activity of newer fluoroquinolones against Stenotrophomonas maltophilia.

PMID- 10933671
TI  - Inhibition of staphylococcal growth by fusidic acid prevents production of
      volatile metabolites.

PMID- 10933672
TI  - In vitro antifungal susceptibility of Alternaria spp. and Ulocladium spp.

PMID- 10933673
TI  - Azole cross-resistance to ketoconazole, fluconazole, itraconazole and
      voriconazole in clinical Candida albicans isolates from HIV-infected children
      with oropharyngeal candidosis.

PMID- 10933674
TI  - Mucocutaneous leishmaniasis associated with HIV infection treated successfully
      with liposomal amphotericin B (AmBisome)

PMID- 10933675
TI  - Increased neutralization sensitivity and reduced replicative capacity of human
      immunodeficiency virus type 1 after short-term in vivo or in vitro passage
      through chimpanzees.
AB  - Development of disease is extremely rare in chimpanzees when inoculated with
      either T-cell-line-adapted neutralization-sensitive or primary human
      immunodeficiency virus type 1 (HIV-1), at first excluding a role for HIV-1
      neutralization sensitivity in the clinical course of infection. Interestingly, we
      observed that short-term in vivo and in vitro passage of primary HIV-1 isolates
      through chimpanzee peripheral blood mononuclear cells (PBMC) resulted in a
      neutralization-sensitive phenotype. Furthermore, an HIV-1 variant reisolated from
      a chimpanzee 10 years after experimental infection was still sensitive to
      neutralization by soluble CD4, the CD4 binding site recognizing antibody IgG1b12
      and autologous chimpanzee serum samples, but had become relatively resistant to
      neutralization by polyclonal human sera and neutralizing monoclonal antibodies.
      The initial adaptation of HIV-1 to replicate in chimpanzee PBMC seemed to
      coincide with a selection for viruses with low replicative kinetics. Neither
      coreceptor usage nor the expression level of CD4, CCR5, or CXCR4 on chimpanzee
      PBMC compared to human cells could explain the phenotypic changes observed in
      these chimpanzee-passaged viruses. Our data suggest that the increased
      neutralization sensitivity of HIV-1 after replication in chimpanzee cells may in
      part contribute to the long-term asymptomatic HIV-1 infection in experimentally
      infected chimpanzees.

PMID- 10933676
TI  - Semliki forest virus budding: assay, mechanisms, and cholesterol requirement.
AB  - All enveloped viruses must bud through a cellular membrane in order to acquire
      their lipid bilayer, but little is known about this important stage in virus
      biogenesis. We have developed a quantitative biochemical assay to monitor the
      budding of Semliki Forest virus (SFV), an enveloped alphavirus that buds from the
      plasma membrane in a reaction requiring both viral spike proteins and
      nucleocapsid. The assay was based on cell surface biotinylation of newly
      synthesized virus spike proteins and retrieval of biotinylated virions using
      streptavidin-conjugated magnetic particles. Budding of biotin-tagged SFV was
      continuous for at least 2 h, independent of microfilaments and microtubules,
      strongly temperature dependent, and relatively independent of continued exocytic
      transport. Studies of cell surface spike proteins at early times of infection
      showed that these spikes did not efficiently bud into virus particles and were
      rapidly degraded. In contrast, at later times of infection, spike protein
      degradation was markedly reduced and efficient budding was then observed. The
      previously described cholesterol requirement in SFV exit was shown to be due to a
      block in budding in the absence of cholesterol and correlated with the continued
      degradation of spike proteins at all times of virus infection in sterol-deficient
      cells.

PMID- 10933677
TI  - Fast screening procedures for random transposon libraries of cloned herpesvirus
      genomes: mutational analysis of human cytomegalovirus envelope glycoprotein
      genes.
AB  - We have cloned the human cytomegalovirus (HCMV) genome as an infectious bacterial
      artificial chromosome (BAC) in Escherichia coli. Here, we have subjected the HCMV
      BAC to random transposon (Tn) mutagenesis using a Tn1721-derived insertion
      sequence and have provided the conditions for excision of the BAC cassette. We
      report on a fast and efficient screening procedure for a Tn insertion library.
      Bacterial clones containing randomly mutated full-length HCMV genomes were
      transferred into 96-well microtiter plates. A PCR screening method based on two
      Tn primers and one primer specific for the desired genomic position of the Tn
      insertion was established. Within three consecutive rounds of PCR a Tn insertion
      of interest can be assigned to a specific bacterial clone. We applied this method
      to retrieve mutants of HCMV envelope glycoprotein genes. To determine the
      infectivities of the mutant HCMV genomes, the DNA of the identified BACs was
      transfected into permissive fibroblasts. In contrast to BACs with mutations in
      the genes coding for gB, gH, gL, and gM, which did not yield infectious virus,
      BACs with disruptions of open reading frame UL4 (gp48) or UL74 (gO) were viable,
      although gO-deficient viruses showed a severe growth deficit. Thus, gO (UL74), a
      component of the glycoprotein complex III, is dispensable for viral growth. We
      conclude that our approach of PCR screening for Tn insertions will greatly
      facilitate the functional analysis of herpesvirus genomes.

PMID- 10933678
TI  - Complex formation between potyvirus VPg and translation eukaryotic initiation
      factor 4E correlates with virus infectivity.
AB  - The interaction between the viral protein linked to the genome (VPg) of turnip
      mosaic potyvirus (TuMV) and the translation eukaryotic initiation factor
      eIF(iso)4E of Arabidopsis thaliana has previously been reported. eIF(iso)4E binds
      the cap structure (m(7)GpppN, where N is any nucleotide) of mRNAs and has an
      important role in the regulation in the initiation of translation. In the present
      study, it was shown that not only did VPg bind eIF(iso)4E but it also interacted
      with the eIF4E isomer of A. thaliana as well as with eIF(iso)4E of Triticum
      aestivum (wheat). The interaction domain on VPg was mapped to a stretch of 35
      amino acids, and substitution of an aspartic acid residue found within this
      region completely abolished the interaction. The cap analogue m(7)GTP, but not
      GTP, inhibited VPg-eIF(iso)4E complex formation, suggesting that VPg and cellular
      mRNAs compete for eIF(iso)4E binding. The biological significance of this
      interaction was investigated. Brassica perviridis plants were infected with a
      TuMV infectious cDNA (p35Tunos) and p35TuD77N, a mutant which contained the
      aspartic acid substitution in the VPg domain that abolished the interaction with
      eIF(iso)4E. After 20 days, plants bombarded with p35Tunos showed viral symptoms,
      while plants bombarded with p35TuD77N remained symptomless. These results suggest
      that VPg-eIF(iso)4E interaction is a critical element for virus production.

PMID- 10933679
TI  - Polarization of allogeneic T-cell responses by influenza virus-infected dendritic
      cells.
AB  - The developing immune response in the lymph nodes of mice infected with influenza
      virus has both Th1- and Th2-type characteristics. Modulation of the interactions
      between antigen-presenting cells and T cells is one mechanism that may alter the
      quality of the immune response. We have previously shown that the ability of
      dendritic cells (DC) to stimulate the proliferation of alloreactive T cells is
      changed by influenza virus due to viral neuraminidase (NA) activity. Here we show
      that DC infected with influenza virus A/PR/8/34 (PR8) stimulate T cells to
      produce different types of cytokines in a dose-dependent manner. Optimal amounts
      of the Th1-type cytokines interleukin-2 (IL-2) and gamma interferon (IFN-gamma)
      were produced from T cells stimulated by DC infected with low doses of PR8, while
      the Th2-type cytokines IL-4 and IL-10 were produced only in response to DC
      infected with high doses of PR8. IL-2 and IFN-gamma levels corresponded with T
      cell proliferation and were dependent on the activity of viral NA on the DC
      surface. In contrast, IL-4 secretion required the treatment of T cells with NA.
      Since viral particles were released only from DC that are infected with high
      doses of PR8, our results suggest that viral NA on newly formed virus particles
      desialylates T-cell surface molecules to facilitate a Th2-type response. These
      results suggest that the activity of NA may contribute to the mixed Th-type
      response observed during influenza virus infection.

PMID- 10933680
TI  - Vaccine protection against simian immunodeficiency virus by recombinant strains
      of herpes simplex virus.
AB  - An effective vaccine for AIDS may require development of novel vectors capable of
      eliciting long-lasting immune responses. Here we report the development and use
      of replication-competent and replication-defective strains of recombinant herpes
      simplex virus (HSV) that express envelope and Nef antigens of simian
      immunodeficiency virus (SIV). The HSV recombinants induced antienvelope antibody
      responses that persisted at relatively stable levels for months after the last
      administration. Two of seven rhesus monkeys vaccinated with recombinant HSV were
      solidly protected, and another showed a sustained reduction in viral load
      following rectal challenge with pathogenic SIVmac239 at 22 weeks following the
      last vaccine administration. HSV vectors thus show great promise for being able
      to elicit persistent immune responses and to provide durable protection against
      AIDS.

PMID- 10933682
TI  - Mechanism of Rep-mediated adeno-associated virus origin nicking.
AB  - The single-stranded adeno-associated virus type 2 (AAV) genome is flanked by
      terminal repeats (TRs) that fold back on themselves to form hairpinned
      structures. During AAV DNA replication, the TRs are nicked by the virus-encoded
      Rep proteins at the terminal resolution site (trs). This origin function
      apparently requires three sequence elements, the Rep binding element (RBE), a
      small palindrome that comprises a single tip of an internal hairpin within the TR
      (RBE'), and the trs. Previously, we determined the sequences at the trs required
      for Rep-mediated cleavage and demonstrated that the trs endonuclease reaction
      occurs in two discrete steps. In the first step, the Rep DNA helicase activity
      unwinds the TR, thereby extruding a stem-loop structure at the trs. In the second
      step, Rep transesterification activity cleaves the trs. Here we investigate the
      contribution of the RBE and RBE' during this process. Our data indicate that Rep
      is tethered to the RBE in a specific orientation during trs nicking. This
      orientation appears to align Rep on the AAV TR, allowing specific nucleotide
      contacts with the RBE' and directing nicking to the trs. Accordingly, alterations
      in the polarity or position of the RBE relative to the trs greatly inhibit Rep
      nicking. Substitutions within the RBE' also reduce Rep specific activity, but to
      a lesser extent. Interestingly, Rep interactions with the RBE and RBE' during
      nicking seem to be functionally distinct. Rep contacts with the RBE appear
      necessary for both the DNA helicase and trs cleavage steps of the endonuclease
      reaction. On the other hand, RBE' contacts seem to be required primarily for TR
      unwinding and formation of the trs stem-loop structure, not cleavage. Together,
      these results suggest a model of Rep interaction with the AAV TR during origin
      nicking through a tripartite cleavage signal comprised of the RBE, the RBE', and
      the trs.

PMID- 10933681
TI  - Analysis of the pore structure of the influenza A virus M(2) ion channel by the
      substituted-cysteine accessibility method.
AB  - The M(2) ion channel of influenza A virus is a small integral membrane protein
      whose active form is a homotetramer with each polypeptide chain containing 96
      amino-acid residues. To identify residues of the transmembrane (TM) domain that
      line the presumed central ion-conducting pore, a set of mutants was generated in
      which each residue of the TM domain (residues 25 to 44) was replaced by cysteine.
      The accessibility of the cysteine mutants to modification by the sulfhydryl
      specific reagents methane thiosulfonate ethylammonium (MTSEA) and MTS
      tetraethylammonium (MTSET) was tested. Extracellular application of MTSEA evoked
      decreases in the conductances measured from two mutants, M(2)-A30C and M(2)-G34C.
      The changes observed were not reversible on washout, indicative of a covalent
      modification. Inhibition by MTSEA, or by the larger reagent MTSET, was not
      detected for residues closer to the extracellular end of the channel than Ala-30,
      indicating the pore may be wider near the extracellular opening. To investigate
      the accessibility of the cysteine mutants to reagents applied intracellularly,
      oocytes were microinjected directly with reagents during recordings. The
      conductance of the M(2)-W41C mutant was decreased by intracellular injection of a
      concentrated MTSET solution. However, intracellular application of MTSET caused
      no change in the conductance of the M(2)-G34C mutant, a result in contrast to
      that obtained when the reagent was applied extracellularly. These data suggest
      that a constriction in the pore exists between residues 34 and 41 which prevents
      passage of the MTS reagent. These findings are consistent with the proposed role
      for His-37 as the selectivity filter. Taken together, these data confirm our
      earlier model that Ala-30, Gly-34, His-37, and Trp-41 line the channel pore (L.
      H. Pinto, G. R. Dieckmann, C. S. Gandhi, C. G. Papworth, J. Braman, M. A.
      Shaughnessy, J. D. Lear, R. A. Lamb, and W. F. DeGrado, Proc. Natl. Acad. Sci.
      USA 94:11301-11306, 1997).

PMID- 10933683
TI  - Formation and characterization of the trimeric form of the fusion protein of
      Semliki Forest Virus.
AB  - Enveloped animal viruses infect cells via fusion of the viral membrane with a
      host cell membrane. Fusion is mediated by a viral envelope glycoprotein, which
      for a number of enveloped animal viruses rearranges itself during fusion to form
      a trimeric alpha-helical coiled-coil structure. This conformational change from
      the metastable, nonfusogenic form of the spike protein to the highly stable form
      involved in fusion can be induced by physiological activators of virus fusion and
      also by a variety of destabilizing conditions. The E1 spike protein subunit of
      Semliki Forest virus (SFV) triggers membrane fusion upon exposure to mildly
      acidic pH and forms a homotrimer that appears necessary for fusion. We have here
      demonstrated that formation of the E1 homotrimer was efficiently triggered under
      low-pH conditions but not by perturbants such as heat or urea, despite their
      induction of generalized conformational changes in the E1 and E2 subunits and
      partial exposure of an acid-specific E1 epitope. We used a sensitive fluorescence
      assay to show that neither heat nor urea treatment triggered SFV-liposome fusion
      at neutral pH, although either treatment inactivated subsequent low-pH-triggered
      fusion activity. Once formed, the low-pH-induced E1 homotrimer was very stable
      and was only dissociated under harsh conditions such as heating in sodium dodecyl
      sulfate. Taken together, these data, as well as protein structure predictions,
      suggest a model in which the less stable native E1 subunit specifically responds
      to low pH to form the more stable E1 homotrimer via conformational changes
      different from those of the coiled-coil type of fusion proteins.

PMID- 10933684
TI  - A new mutant class, made by targeted mutagenesis, of phage PRD1 reveals that
      protein P5 connects the receptor binding protein to the vertex.
AB  - Phage PRD1 and adenovirus share a number of structural and functional
      similarities, one of which is the vertex organization at the fivefold-symmetry
      positions. We developed an in vitro mutagenesis system for the linear PRD1 genome
      in order to make targeted mutations. The role of protein P5 in the vertex
      structure was examined by this method. Mutation in gene V revealed that protein
      P5 is essential. The absence of P5 did not compromise the particle assembly or
      DNA packaging but led to a deficient vertex structure where the receptor binding
      protein P2, in addition to protein P5, was missing. P5(-) particles also lost
      their DNA upon purification. Based on this and previously published information
      we propose a spatial model for the spike structure at the vertices. This
      resembles to the corresponding structure in adenovirus.

PMID- 10933685
TI  - DNA vaccines for influenza virus: differential effects of maternal antibody on
      immune responses to hemagglutinin and nucleoprotein.
AB  - Maternal antibody is the major form of protection from disease in early life when
      the neonatal immune system is still immature; however, the presence of maternal
      antibody also interferes with active immunization, placing infants at risk for
      severe bacterial and viral infection. We tested the ability of intramuscular and
      gene gun immunization with DNA expressing influenza virus hemagglutinin (HA) and
      nucleoprotein (NP) to raise protective humoral and cellular responses in the
      presence or absence of maternal antibody. Neonatal mice born to influenza virus
      immune mothers raised full antibody responses to NP but failed to generate
      antibody responses to HA. In contrast, the presence of maternal antibody did not
      affect the generation of long-lived CD8(+) T-cell responses to both HA and NP.
      Thus, maternal antibody did not affect cell-mediated responses but did affect
      humoral responses, with the ability to limit the antibody response correlating
      with whether the DNA-expressed immunogen was localized in the plasma membrane or
      within the cell.

PMID- 10933686
TI  - The synthetic immunomodulator murabutide controls human immunodeficiency virus
      type 1 replication at multiple levels in macrophages and dendritic cells.
AB  - Macrophages and dendritic cells are known to play an important role in the
      establishment and persistence of human immunodeficiency virus (HIV) infection.
      Besides antiretroviral therapy, several immune-based interventions are being
      evaluated with the aim of achieving better control of virus replication in
      reservoir cells. Murabutide is a safe synthetic immunomodulator presenting a
      capacity to enhance nonspecific resistance against viral infections and to target
      cells of the reticuloendothelial system. In this study, we have examined the
      ability of Murabutide to control HIV type 1 (HIV-1) replication in acutely
      infected monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Highly
      significant suppression of viral replication was consistently observed in
      Murabutide-treated cultures of both cell types. Murabutide did not affect virus
      entry, reverse transcriptase activity, or early proviral DNA formation in the
      cytoplasm of infected cells. However, treated MDMs and MDDCs showed a dramatic
      reduction in nuclear viral two-long terminal repeat circular form and viral mRNA
      transcripts. This HIV-1-suppressive activity was not mediated by inhibiting
      cellular DNA synthesis or by activating p38 mitogen-activated protein kinase.
      Furthermore, Murabutide-stimulated cells expressed reduced CD4 and CCR5 receptors
      and secreted high levels of beta-chemokines, although neutralization of the
      released chemokines did not alter the HIV-1-suppressive activity of Murabutide.
      These results provide evidence that a clinically acceptable immunomodulator can
      activate multiple effector pathways in macrophages and in dendritic cells,
      rendering them nonpermissive for HIV-1 replication.

PMID- 10933687
TI  - MM1, a temperate bacteriophage of the type 23F Spanish/USA multiresistant
      epidemic clone of Streptococcus pneumoniae: structural analysis of the site
      specific integration system.
AB  - We have characterized a temperate phage (MM1) from a clinical isolate of the
      multiply antibiotic-resistant Spanish/American 23F Streptococcus pneumoniae clone
      (Spain(23F)-1 strain). The 40-kb double-stranded genome of MM1 has been isolated
      as a DNA-protein complex. The use of MM1 DNA as a probe revealed that the phage
      genome is integrated in the host chromosome. The host and phage attachment sites,
      attB and attP, respectively, have been determined. Nucleotide sequencing of the
      attachment sites identified a 15-bp core site (5'-TTATAATTCATCCGC-3') that has
      not been found in any bacterial genome described so far. Sequence information
      revealed the presence of an integrase gene (int), which represents the first
      identification of an integrase in the pneumococcal system. A 1.5-kb DNA fragment
      embracing attP and the int gene contained all of the genetic information needed
      for stable integration of a nonreplicative plasmid into the attB site of a
      pneumococcal strain. This vector will facilitate the introduction of foreign
      genes into the pneumococcal chromosome. Interestingly, DNAs highly similar to
      that of MM1 have been detected in several clinical pneumococcal isolates of
      different capsular types, suggesting a widespread distribution of these phages in
      relevant pathogenic strains.

PMID- 10933688
TI  - Infection of human cells by dengue virus is modulated by different cell types and
      viral strains.
AB  - Although prior studies have investigated cellular infection by dengue virus (DV),
      many have used highly passaged strains. We have reassessed cellular infection by
      DV type 2 (DV2) using prototype and low-passage isolates representing genotypes
      from different geographic areas. We observed marked variation in the
      susceptibility to infection among cell types by different DV2 strains. HepG2
      hepatoma cells were susceptible to infection by all DV2 strains assayed. Although
      the prototype strain generated higher titers of secreted virus than the low
      passage isolates, this difference did not correspond to positive- or negative
      strand viral RNA levels and thus may reflect variation in efficiency among DV2
      isolates to translate viral proteins or package and/or secrete virus. In
      contrast, human foreskin fibroblasts were susceptible to the prototype and low
      passage Thai isolates but not to five Nicaraguan strains tested, as reflected by
      the absence of accumulation of negative-strand viral RNA, viral antigen, and
      infectious virus. A similar pattern was observed with the antibody-dependent
      pathway of infection. U937 and THP-1 myeloid cells and peripheral blood monocytes
      were infected in the presence of enhancing antibodies by the prototype strain but
      not by low-passage Nicaraguan isolates. Again, the barrier appeared to be prior
      to negative-strand accumulation. Thus, depending on the cell type and viral
      isolate, blocks that limit the production of infectious virus in vitro may occur
      at distinct steps in the pathway of cellular infection.

PMID- 10933690
TI  - Involvement of the zinc-binding capacity of Sendai virus V protein in viral
      pathogenesis.
AB  - The V protein of Sendai virus (SeV) is nonessential to virus replication in cell
      culture but indispensable to viral pathogenicity in mice. The highly conserved
      cysteine-rich zinc finger-like domain in its carboxyl terminus is believed to be
      responsible for this viral pathogenicity. In the present study, we showed that
      the cysteine-rich domain of the SeV V protein could actually bind zinc by using
      glutathione-S-transferase fusion proteins. When the seven conserved cysteine
      residues at positions 337, 341, 353, 355, 358, 362, and 365 were replaced
      individually, the zinc-binding capacities of the mutant proteins were greatly
      impaired, ranging from 22 to 68% of that of the wild type. We then recovered two
      mutant SeVs from cDNA, which have V-C(341)S and V-C(365)R mutations and represent
      maximal and minimal zinc-binding capacities among the corresponding mutant fusion
      proteins, respectively. The mutant viruses showed viral protein synthesis and
      growth patterns similar to those of wild-type SeV in cultured cells. However, the
      mutant viruses were strongly attenuated in mice in a way similar to that of SeV
      V(DeltaC), which has a truncated V protein lacking the cysteine-rich domain, by
      exhibiting earlier viral clearance from the mouse lung and less virulence to
      mice. We therefore conclude that the zinc-binding capacity of the V protein is
      involved in viral pathogenesis.

PMID- 10933689
TI  - Characterization of chemokine receptor utilization of viruses in the latent
      reservoir for human immunodeficiency virus type 1.
AB  - Latently infected resting CD4(+) T cells provide a long-term reservoir for human
      immunodeficiency virus type 1 (HIV-1) and are likely to represent the major
      barrier to virus eradication in patients on combination antiretroviral therapy.
      The mechanisms by which viruses enter the latent reservoir and the nature of the
      chemokine receptors involved have not been determined. To evaluate the phenotype
      of the virus in this compartment with respect to chemokine receptor utilization,
      full-length HIV-1 env genes were cloned from latently infected cells and assayed
      functionally. We demonstrate that the majority of the viruses in the latent
      reservoir utilize CCR5 during entry, although utilization of several other
      receptors, including CXCR4, was observed. No alternative coreceptors were shown
      to be involved in a systematic fashion. Although R5 viruses are present in the
      latent reservoir, CCR5 was not expressed at high levels on resting CD4(+) T
      cells. To understand the mechanism by which R5 viruses enter latent reservoir,
      the ability of an R5 virus, HIV-1 Ba-L, to infect highly purified resting CD4(+)
      T lymphocytes from uninfected donors was evaluated. Entry of Ba-L could be
      observed when virus was applied at a multiplicity approaching 1. However,
      infection was limited to a subset of cells expressing low levels of CCR5 and
      markers of immunologic memory. Naive cells could not be infected by an R5 virus
      even when challenged with a large inoculum. Direct cell fractionation studies
      showed that latent virus is present predominantly in resting memory cells but
      also at lower levels in resting naive cells. Taken together, these findings
      provide support for the hypothesis that the direct infection of naive T cells is
      not the major mechanism by which the latent infection of resting T cells is
      established.

PMID- 10933691
TI  - E2F proteins are posttranslationally modified concomitantly with a reduction in
      nuclear binding activity in cells infected with herpes simplex virus 1.
AB  - The transition from G(1) to S phase in the cell cycle requires sequential
      activation of cyclin-dependent kinase 4 (cdk4) and cdk2, which phosphorylate the
      retinoblastoma protein, causing the release of E2F. Free E2F upregulates the
      transcription of genes involved in S phase and cell cycle progression. Recent
      studies from this and other laboratories have shown that herpes simplex virus 1
      stabilizes cyclin D3 early in infection and that early events in viral
      replication are sensitive to inhibitors of some cdks. On the other hand cdk2 is
      not activated. Here we report studies on the status of members of E2F family in
      cycling HEp-2 and HeLa cells and quiescent serum-starved, contact-inhibited human
      lung fibroblasts. The results show that (i) at 8 h postinfection or thereafter,
      E2F-1 and E2F-5 were posttranslationally modified and/or translocated from
      nucleus to the cytoplasm, (ii) E2F-4 was hyperphophorylated, and (iii) overall,
      E2F binding to cognate DNA sites was decreased at late times after infection.
      These results concurrent with those cited above indicate that late in infection
      activation of S-phase genes is blocked both by posttranslational modification and
      translocation of members of E2F family to inactive compartments and by the
      absence of active cdk2. The observation that E2F were also posttranslationally
      modified in quiescent human lung fibroblasts that were not in S phase at the time
      of infection suggests that specific viral gene products are responsible for
      modification of the members of E2F family and raises the possibility that in
      infected cells, activation of the S phase gene is an early event in viral
      infection and is then shut off at late times. This is consistent with the timing
      of stabilization of cyclin D3 and the events blocked by inhibitors of cdks.

PMID- 10933692
TI  - Simian-human immunodeficiency virus containing a human immunodeficiency virus
      type 1 subtype-E envelope gene: persistent infection, CD4(+) T-cell depletion,
      and mucosal membrane transmission in macaques.
AB  - The envelope (env) glycoprotein of human immunodeficiency virus type 1 (HIV-1)
      determines several viral properties (e.g., coreceptor usage, cell tropism, and
      cytopathicity) and is a major target of antiviral immune responses. Most
      investigations on env have been conducted on subtype-B viral strains, prevalent
      in North America and Europe. Our study aimed to analyze env genes of subtype-E
      viral strains, prevalent in Asia and Africa, with a nonhuman primate model for
      lentivirus infection and AIDS. To this end, we constructed a simian
      immunodeficiency virus/HIV-1 subtype-E (SHIV) recombinant clone by replacing the
      env ectodomain of the SHIV-33 clone with the env ectodomain from the subtype-E
      strain HIV-1(CAR402), which was isolated from an individual in the Central
      African Republic. Virus from this recombinant clone, designated SHIV-E-CAR,
      replicated efficiently in macaque peripheral blood mononuclear cells.
      Accordingly, juvenile macaques were inoculated with cell-free SHIV-E-CAR by the
      intravenous or intravaginal route; virus replicated in these animals but did not
      produce hematological abnormalities. In an attempt to elicit the pathogenic
      potential of the recombinant clone, we serially passaged this viral clone via
      transfusion of blood and bone marrow through juvenile macaques to produce SHIV-E
      P4 (fourth-passage virus). The serially passaged virus established productive
      infection and CD4(+) T-cell depletion in juvenile macaques inoculated by either
      the intravenous or the intravaginal route. Determination of the coreceptor usage
      of SHIV-E-CAR and serially passaged SHIV-E-P4 indicated that both of these
      viruses utilized CXCR4 as a coreceptor. In summary, the serially passaged SHIV
      subtype-E chimeric virus will be important for studies aimed at developing a
      nonhuman primate model for analyzing the functions of subtype-E env genes in
      viral transmission and pathogenesis and for vaccine challenge experiments with
      macaques immunized with HIV-1 env antigens.

PMID- 10933693
TI  - Macrophages escape inhibition of major histocompatibility complex class I
      dependent antigen presentation by cytomegalovirus.
AB  - The mouse cytomegalovirus (MCMV) m152- and m06-encoded glycoproteins gp40 and
      gp48, respectively, independently downregulate major histocompatibility complex
      (MHC) class I surface expression during the course of productive MCMV infection
      in fibroblasts. As a result, presentation of an immediate-early protein pp89
      derived nonapeptide to H-2L(d)-restricted CD8(+) cytotoxic T cells is completely
      prevented in fibroblasts. Here we demonstrate that MCMV-infected primary bone
      marrow macrophages and the macrophage cell line J774 constitutively present pp89
      peptides during permissive MCMV infection to cytotoxic T lymphocytes (CTL). In
      contrast to fibroblasts, expression of the m152 and m06 genes in macrophages does
      not affect surface expression of MHC class I. Assessment of pp89 synthesis and
      quantification of extracted peptide revealed a significantly higher efficiency of
      macrophages than of fibroblasts to process pp89 into finally trimmed peptide. The
      yield of pp89 peptide determined in MCMV-infected tissues of bone marrow chimeras
      confirmed that bone marrow-derived cells represent a prime source of pp89
      processing in parenchymal organs. The finding that macrophages resist the viral
      control of MHC I-dependent antigen presentation reconciles the paradox of
      efficient induction of CMV-specific CD8(+) CTL in vivo despite extensive
      potential of CMVs to subvert MHC class I.

PMID- 10933694
TI  - Induction of p53-independent apoptosis by the adenovirus E4orf4 protein requires
      binding to the Balpha subunit of protein phosphatase 2A.
AB  - Previous studies have indicated that the E4orf4 protein of human adenovirus type
      2 (Ad2) induces p53-independent apoptosis. We believe that this process may play
      a role in cell death and viral spread at the final stages of productive
      infection. E4orf4 may also be of therapeutic value in treating some diseases,
      including cancer, through its ability to induce apoptosis when expressed
      individually. The only previously identified biochemical function of E4orf4 is
      its ability to associate with the Balpha subunit of protein phosphatase 2A
      (PP2A). We have used a genetic approach to determine the role of such
      interactions in E4orf4-induced cell death. E4orf4 deletion mutants were of only
      limited value, as all were highly defective. We found that E4orf4 proteins from
      most if not all adenovirus serotypes induced cell death, and thus point mutations
      were introduced that converted the majority of highly conserved residues to
      alanines. Such mutants were used to correlate Balpha-subunit binding, association
      with PP2A activity, and cell killing following the transfection of appropriate
      cDNAs into p53-null H1299 or C33A cells. The results indicated that binding of
      the Balpha subunit is essential for induction of cell death, as every mutant that
      failed to bind efficiently was totally defective for cell killing. This class of
      mutations (class I) largely involved residues between amino acids 51 and 89.
      Almost all E4orf4 mutant proteins that associated with PP2A killed cancer cells
      at high levels; however, several mutants that associated with significant levels
      of PP2A were defective for killing (class II). Thus, binding of E4orf4 to PP2A is
      essential for induction of p53-independent apoptosis, but E4orf4 may possess one
      or more additional functions required for cell killing.

PMID- 10933695
TI  - Sequence variability of Borna disease virus: resistance to superinfection may
      contribute to high genome stability in persistently infected cells.
AB  - The RNA genome of Borna disease virus (BDV) shows extraordinary stability in
      persistently infected cell cultures. We performed bottleneck experiments in which
      virus populations from single infected cells were allowed to spread through
      cultures of uninfected cells and in which RNase protection assays were used to
      identify virus variants with mutations in a 535-nucleotide fragment of the M-G
      open reading frames. In one of the cell cultures, the major virus species
      (designated 2/1) was a variant with two point mutations in the G open reading
      frame. When fresh cells were infected with a low dose of a virus stock prepared
      from 2/1-containing cells, only a minority of the resulting persistently infected
      cultures contained detectable levels of the variant, whereas the others all
      seemed to contain wild-type virus. The BDV variant 2/1 remained stable in the
      various persistently infected cell cultures, indicating that the cells were
      resistant to superinfection by wild-type virus. Indeed, cells persistently
      infected with prototype BDV He/80 were also found to resist superinfection with
      strain V and vice versa. Our screen for mutations in the viral M and G genes of
      different rat-derived BDV virus stocks revealed that only one of four stocks
      believed to contain He/80 harbored virus with the original sequence. Two stocks
      mainly contained a novel virus variant with about 3% sequence divergence, whereas
      the fourth stock contained a mixture of both viruses. When the mixture was
      inoculated into the brains of newborn mice, the novel variant was preferentially
      amplified. These results provide evidence that the BDV genome is mutating more
      frequently than estimated from its invariant appearance in persistently infected
      cell cultures and that resistance to superinfection might strongly select against
      novel variants.

PMID- 10933696
TI  - Mutations in the 5' nontranslated region of bovine viral diarrhea virus result in
      altered growth characteristics.
AB  - The 5' nontranslated region (NTR) of pestiviruses functions as an internal
      ribosome entry site (IRES) that mediates cap-independent translation of the viral
      polyprotein and probably contains additional cis-acting RNA signals involved in
      crucial processes of the viral life cycle. Computer modeling suggests that the 5'
      terminal 75 nucleotides preceding the IRES element form two stable hairpins, Ia
      and Ib. Spontaneous and engineered mutations located in the genomic region
      comprising Ia and Ib were characterized by using infectious cDNA clones of bovine
      viral diarrhea virus. Spontaneous 5' NTR mutations carrying between 9 and 26 A
      residues within the loop region of Ib had no detectable influence on specific
      infectivity and virus growth properties. After tissue culture passages, multiple
      insertions and deletions of A residues occurred rapidly. In contrast, an
      engineered mutant carrying 5 A residues within the Ib loop was genetically stable
      during 10 tissue culture passages. This virus was used as starting material to
      generate a number of additional mutants. The analyses show that (i) deletion of
      the entire Ib loop region resulted in almost complete loss of infectivity that
      was rapidly restored during passages in cell culture by insertions of variable
      numbers of A residues; (ii) mutations within the 5'-terminal 4 nucleotides of the
      genomic RNA severely impaired virus replication; passaging of the supernatants
      obtained after transfection resulted in the emergence of efficiently replicating
      mutants that had regained the conserved 5'-terminal sequence; (iii) provided the
      conserved sequence motif 5'-GUAU was retained at the 5' end of the genomic RNA,
      substitutions and deletions of various parts of hairpin Ia or deletion of all of
      Ia and part of Ib were found to support replication, but to a lower degree than
      the parent virus. Restriction of specific infectivity and virus growth of the 5'
      NTR mutants correlated with reduced amounts of accumulated viral RNAs.

PMID- 10933697
TI  - Moving the glycoprotein gene of vesicular stomatitis virus to promoter-proximal
      positions accelerates and enhances the protective immune response.
AB  - Vesicular stomatitis virus (VSV) is the prototype of the Rhabdoviridae and
      contains nonsegmented negative-sense RNA as its genome. The 11-kb genome encodes
      five genes in the order 3'-N-P-M-G-L-5', and transcription is obligatorily
      sequential from the single 3' promoter. As a result, genes at promoter-proximal
      positions are transcribed at higher levels than those at promoter-distal
      positions. Previous work demonstrated that moving the gene encoding the
      nucleocapsid protein N to successively more promoter-distal positions resulted in
      stepwise attenuation of replication and lethality for mice. In the present study
      we investigated whether moving the gene for the attachment glycoprotein G, which
      encodes the major neutralizing epitopes, from its fourth position up to first in
      the gene order would increase G protein expression in cells and alter the immune
      response in inoculated animals. In addition to moving the G gene alone, we also
      constructed viruses having both the G and N genes rearranged. This produced three
      variant viruses having the orders 3'-G-N-P-M-L-5' (G1N2), 3'-P-M-G-N-L-5' (G3N4),
      and 3'-G-P-M-N-L-5' (G1N4), respectively. These viruses differed from one another
      and from wild-type virus in their levels of gene expression and replication in
      cell culture. The viruses also differed in their pathogenesis, immunogenicity,
      and level of protection of mice against challenge with wild-type VSV.
      Translocation of the G gene altered the kinetics and level of the antibody
      response in mice, and simultaneous reduction of N protein expression reduced
      replication and lethality for animals. These studies demonstrate that gene
      rearrangement can be exploited to design nonsegmented negative-sense RNA viruses
      that have characteristics desirable in candidates for live attenuated vaccines.

PMID- 10933698
TI  - Role of viral persistence in retaining CD8(+) T cells within the central nervous
      system.
AB  - The continued presence of virus-specific CD8(+) T cells within the central
      nervous system (CNS) following resolution of acute viral encephalomyelitis
      implicates organ-specific retention. The role of viral persistence in locally
      maintaining T cells was investigated by infecting mice with either a
      demyelinating, paralytic (V-1) or nonpathogenic (V-2) variant of a neurotropic
      mouse hepatitis virus, which differ in the ability to persist within the CNS.
      Class I tetramer technology revealed more infiltrating virus-specific CD8(+) T
      cells during acute V-1 compared to V-2 infection. However, both total and virus
      specific CD8(+) T cells accumulated at similar peak levels in spinal cords by day
      10 postinfection (p.i.). Decreasing viral RNA levels in both brains and spinal
      cords following initial virus clearance coincided with an overall progressive
      loss of both total and virus-specific CD8(+) T cells. By 9 weeks p.i., T cells
      had largely disappeared from brains of both infected groups, consistent with the
      decline of viral RNA. T cells also completely disappeared from V-2-infected
      spinal cords coincident with the absence of viral RNA. By contrast, a significant
      number of CD8(+) T cells which contained detectable viral RNA were recovered from
      spinal cords of V-1-infected mice. The data indicate that residual virus from a
      primary CNS infection is a vital component in mediating local retention of both
      CD8(+) and CD4(+) T cells and that once minimal thresholds of stimuli are lost, T
      cells within the CNS cannot survive in an autonomous fashion.

PMID- 10933699
TI  - Identification of mouse hepatitis virus papain-like proteinase 2 activity.
AB  - Mouse hepatitis virus (MHV) is a 31-kb positive-strand RNA virus that is
      replicated in the cytoplasm of infected cells by a viral RNA-dependent RNA
      polymerase, termed the replicase. The replicase is encoded in the 5'-most 22 kb
      of the genomic RNA, which is translated to produce a polyprotein of >800 kDa. The
      replicase polyprotein is extensively processed by viral and perhaps cellular
      proteinases to give rise to a functional replicase complex. To date, two of the
      MHV replicase-encoded proteinases, papain-like proteinase 1 (PLP1) and the
      poliovirus 3C-like proteinase (3CLpro), have been shown to process the replicase
      polyprotein. In this report, we describe the cloning, expression, and activity of
      the third MHV proteinase domain, PLP2. We show that PLP2 cleaves a substrate
      encoding the first predicted membrane-spanning domain (MP1) of the replicase
      polyprotein. Cleavage of MP1 and release of a 150-kDa intermediate, p150, are
      likely to be important for embedding the replicase complex in cellular membranes.
      Using an antiserum (anti-D11) directed against the C terminus of the MP1 domain,
      we verified that p150 encompasses the MP1 domain and identified a 44-kDa protein
      (p44) as a processed product of p150. Pulse-chase experiments showed that p150 is
      rapidly generated in MHV-infected cells and that p44 is processed from the p150
      precursor. Protease inhibitor studies revealed that unlike 3CLpro activity, PLP2
      activity is not sensitive to cysteine protease inhibitor E64d. Furthermore,
      coexpression studies using the PLP2 domain and a substrate encoding the MP1
      cleavage site showed that PLP2 acts efficiently in trans. Site-directed
      mutagenesis studies confirmed the identification of cysteine 1715 as a catalytic
      residue of PLP2. This study is the first to report enzymatic activity of the PLP2
      domain and to demonstrate that three distinct viral proteinase activities process
      the MHV replicase polyprotein.

PMID- 10933701
TI  - Existence of distinct GB virus C/hepatitis G virus variants with different
      tropism.
AB  - To study the existence of GB virus C/hepatitis G virus (GBV-C/HGV) variants with
      different tropism, we have analyzed the heterogeneity and quasispecies
      composition of GBV-C/HGV isolated from in vitro-infected peripheral blood
      mononuclear cells (PBMC) and from sera, livers, and PBMC from two chronically
      infected patients. For this purpose, the GBV-C/HGV 5' noncoding region (5'NCR)
      was amplified by reverse transcription-PCR and the amplified products were cloned
      and sequenced. These analyses showed that the master 5'NCR sequences isolated
      from the in vitro-infected PBMC and from the PBMC isolated from the patient whose
      serum was used as the inoculum were identical but different from that of the
      inoculum. Furthermore, phylogenetic analysis revealed that all PBMC sequences
      grouped together into a branch which was separate from those of the inoculum. For
      one of the two chronically infected patients, all the sequences from the PBMC and
      one from the liver clustered into a single branch while the sequences from the
      serum and all the other liver sequences grouped together in the other branch. For
      the other patient, the sequences from the serum and PBMC and three sequences from
      the liver grouped together into one branch, while the remaining five sequences
      from the liver were separated in a different cluster. In conclusion, our results
      support the existence of different GBV-C/HGV variants with different tissue
      tropism.

PMID- 10933700
TI  - Characterization and epitope mapping of neutralizing monoclonal antibodies
      produced by immunization with oligomeric simian immunodeficiency virus envelope
      protein.
AB  - In an attempt to generate broadly cross-reactive, neutralizing monoclonal
      antibodies (MAbs) to simian immunodeficiency virus (SIV), we compared two
      immunization protocols using different preparations of oligomeric SIV envelope
      (Env) glycoproteins. In the first protocol, mice were immunized with soluble
      gp140 (sgp140) from CP-MAC, a laboratory-adapted variant of SIVmacBK28.
      Hybridomas were screened by enzyme-linked immunosorbent assay, and a panel of 65
      MAbs that recognized epitopes throughout the Env protein was generated. In
      general, these MAbs detected Env by Western blotting, were at least weakly
      positive in fluorescence-activated cell sorting (FACS) analysis of Env-expressing
      cells, and preferentially recognized monomeric Env protein. A subset of these
      antibodies directed toward the V1/V2 loop, the V3 loop, or nonlinear epitopes
      were capable of neutralizing CP-MAC, a closely related isolate (SIVmac1A11),
      and/or two more divergent strains (SIVsmDeltaB670 CL3 and SIVsm543-3E). In the
      second protocol, mice were immunized with unfixed CP-MAC-infected cells and MAbs
      were screened for the ability to inhibit cell-cell fusion. In contrast to MAbs
      generated against sgp140, the seven MAbs produced using this protocol did not
      react with Env by Western blotting and were strongly positive by FACS analysis,
      and several reacted preferentially with oligomeric Env. All seven MAbs potently
      neutralized SIVmac1A11, and several neutralized SIVsmDeltaB670 CL3 and/or
      SIVsm543-3E. MAbs that inhibited gp120 binding to CD4, CCR5, or both were
      identified in both groups. MAbs to the V3 loop and one MAb reactive with the
      V1/V2 loop interfered with CCR5 binding, indicating that these regions of Env
      play similar roles for SIV and human immunodeficiency virus. Remarkably, several
      of the MAbs generated against infected cells blocked CCR5 binding in a V3
      independent manner, suggesting that they may recognize a region analogous to the
      conserved coreceptor binding site in gp120. Finally, all neutralizing MAbs
      blocked infection through the alternate coreceptor STRL33 much more efficiently
      than infection through CCR5, a finding that has important implications for SIV
      neutralization assays using CCR5-negative human T-cell lines.

PMID- 10933702
TI  - Poxvirus-induced immunostimulating effects on porcine leukocytes.
AB  - The prophylactic application of inactivated parapox ovis viruses (Baypamun; Bayer
      AG, Leverkusen, Germany) has been shown to reduce efficiently the outbreak of
      stress-mediated diseases in different species. However, little is known about the
      basic mechanism behind this observed stimulatory property. We therefore tested
      eight inactivated poxvirus strains belonging to three different genera
      (Orthopoxvirus, Avipoxvirus, and Parapoxvirus) for their capacity to activate
      cells of the porcine innate and specific immune systems in vitro. The results
      indicated that poxviruses failed to induce increased phagocytosis, oxidative
      burst, or natural killer cell activity in swine. In contrast, enhanced release of
      interleukin-2, alpha interferon, and gamma interferon, as well as strong
      proliferation, could be measured. Flow cytometric analyses and cell sorting
      experiments identified T-helper cells as the main target responding to
      inactivated poxviruses: the activated cells had a CD4(high) CD25(+) major
      histocompatibility complex type II-positive phenotype and were the major source
      of secreted cytokines. Together, the results demonstrated that all tested
      poxviruses possessed immunostimulating capacity. These in vitro poxvirus-induced
      effects may be responsible at least in part for the in vivo immunostimulating
      capacity of inactivated poxviruses.

PMID- 10933703
TI  - Coxsackievirus expression of the murine secretory protein interleukin-4 induces
      increased synthesis of immunoglobulin G1 in mice.
AB  - We cloned the sequence encoding murine interleukin-4 (mIL-4), including the
      secretory signal, into the genome of CVB3/0, an artificially attenuated strain of
      coxsackievirus B3, at the junction of the capsid protein 1D and the viral
      protease 2Apro. Two strains of chimeric CVB3 were constructed using, in one case,
      identical sequences to encode 2Apro cleavage sites (CVB3/0-mIL4/47) on either
      side of the inserted coding sequence and, in the other case, nonidentical
      sequences that varied at the nucleotide level without changing the amino acid
      sequences (CVB3-PL2-mIL4/46). Transfection of HeLa cells yielded progeny viruses
      that replicated with rates similar to that of the parental CVB3/0 strain,
      although yields of mIL-4-expressing strains were approximately 10-fold lower than
      those of the parental virus. Western blot analysis of viral proteins isolated
      from HeLa cells inoculated with either strain of chimeric virus demonstrated that
      the chimeric viruses synthesized capsid protein 1D at approximately twofold
      higher levels than the parental virus. mIL-4 protein was detected by enzyme
      linked immunosorbent assay (ELISA) in HeLa cells inoculated with either strain of
      chimeric virus. Lysates of HeLa cells inoculated with either chimeric virus
      induced the proliferation of the mIL-4-requiring murine MC-9 cell line,
      demonstrating biological activity of the CVB3-expressed mIL-4. Reverse
      transcription (RT)-PCR analysis of viral RNA derived from sequential passaging of
      CVB3/0-mIL4/47 in HeLa cells demonstrated deletion of the mIL-4 coding sequence
      occurring by the fourth passage, while similar analysis of CVB3-PL2-mIL4/46 RNA
      demonstrated detection of the mIL-4 coding sequence in the virus population
      through 10 generations in HeLa cells. mIL-4 protein levels determined by ELISA
      were consistent with the stability and loss data determined by RT-PCR analysis of
      the passaged viral genomes. Studies of insert stability of CVB3-PL2-mIL4/46
      during replication in mice showed the presence of the viral mIL-4 insert in
      pancreas, heart, and liver at 14 days postinfection. Comparison of the murine
      antibody responses to CVB3-PL2-mIL4/46 and the parental CVB3/0 strain
      demonstrated an increased level of CVB3-binding serum immunoglobulin G1 in mice
      inoculated with CVB3-PL2-mIL4/46.

PMID- 10933704
TI  - Construction, phenotypic analysis, and immunogenicity of a UL5/UL29 double
      deletion mutant of herpes simplex virus 2.
AB  - A number of studies have shown that replication-defective mutant strains of
      herpes simplex virus (HSV) can induce protective immunity in animal systems
      against wild-type HSV challenge. However, all of those studies used viruses with
      single mutations. Because multiple, stable mutations provide optimal levels of
      safety for live vaccines, we felt that additional mutations needed to be
      engineered into a candidate vaccine strain for HSV-2 and genital herpes. We
      therefore isolated an HSV-2 strain with deletion mutations in two viral DNA
      replication protein genes, UL5 and UL29. The resulting double deletion mutant
      virus strain, dl5-29, fails to form plaques or to give any detectable single
      cycle yields in normal monkey or human cells. Nevertheless, dl5-29 expresses
      nearly the same pattern of gene products as the wild-type virus or the single
      mutant viruses and induces antibody titers in mice that are equivalent to those
      induced by single deletion mutant viruses. Therefore, it is feasible to isolate a
      mutant HSV strain with two mutations in essential genes and with an increased
      level of safety but which is still highly immunogenic.

PMID- 10933705
TI  - In vitro and in vivo infection of neural cells by a recombinant measles virus
      expressing enhanced green fluorescent protein.
AB  - This study focused on the in vitro infection of mouse and human neuroblastoma
      cells and the in vivo infection of the murine central nervous system with a
      recombinant measles virus. An undifferentiated mouse neuroblastoma cell line
      (TMN) was infected with the vaccine strain of measles virus (MVeGFP), which
      expresses enhanced green fluorescent protein (EGFP). MVeGFP infected the cells,
      and cell-to-cell spread was studied by virtue of the resulting EGFP
      autofluorescence, using real-time confocal microscopy. Cells were differentiated
      to a neuronal phenotype, and extended processes, which interconnected the cells,
      were observed. It was also possible to infect the differentiated neuroblastoma
      cells (dTMN) with MVeGFP. Single autofluorescent EGFP-positive cells were
      selected at the earliest possible point in the infection, and the spread of EGFP
      autofluorescence was monitored. In this instance the virus used the
      interconnecting processes to spread from cell to cell. Human neuroblastoma cells
      (SH-SY-5Y) were also infected with MVeGFP. The virus infected these cells, and
      existing processes were used to initiate new foci of infection at distinct
      regions of the monolayer. Transgenic animals expressing CD46, a measles virus
      receptor, and lacking interferon type 1 receptor gene were infected
      intracerebrally with MVeGFP. A productive infection ensued, and the mice
      exhibited clinical signs of infection, such as ataxia and an awkward gait,
      identical to those previously observed for the parental virus (Edtag). Mice were
      sacrificed, and brain sections were examined for EGFP autofluorescence by
      confocal scanning laser microscopy over a period of 6 h. EGFP was detected in
      discrete focal regions of the brain and in processes, which extended deep into
      the parenchyma. Collectively, these results indicate (i) that MVeGFP can be used
      to monitor virus replication sensitively, in real time, in animal tissues, (ii)
      that infection of ependymal cells and neuroblasts provides a route by which
      measles virus can enter the central nervous system in mouse models of
      encephalitis, and (iii) that upon infection, the virus spreads transneuronally.

PMID- 10933707
TI  - Activation of interferon regulatory factor 3 is inhibited by the influenza A
      virus NS1 protein.
AB  - We present a novel mechanism by which viruses may inhibit the alpha/beta
      interferon (IFN-alpha/beta) cascade. The double-stranded RNA (dsRNA) binding
      protein NS1 of influenza virus is shown to prevent the potent antiviral
      interferon response by inhibiting the activation of interferon regulatory factor
      3 (IRF-3), a key regulator of IFN-alpha/beta gene expression. IRF-3 activation
      and, as a consequence, IFN-beta mRNA induction are inhibited in wild-type (PR8)
      influenza virus-infected cells but not in cells infected with an isogenic virus
      lacking the NS1 gene (delNS1 virus). Furthermore, NS1 is shown to be a general
      inhibitor of the interferon signaling pathway. Inhibition of IRF-3 activation can
      be achieved by the expression of wild-type NS1 in trans, not only in delNS1 virus
      infected cells but also in cells infected with a heterologous RNA virus
      (Newcastle disease virus). We propose that inhibition of IRF-3 activation by a
      dsRNA binding protein significantly contributes to the virulence of influenza A
      viruses and possibly to that of other viruses.

PMID- 10933706
TI  - The genome of a very virulent Marek's disease virus.
AB  - Here we present the first complete genomic sequence, with analysis, of a very
      virulent strain of Marek's disease virus serotype 1 (MDV1), Md5. The genome is
      177,874 bp and is predicted to encode 103 proteins. MDV1 is colinear with the
      prototypic alphaherpesvirus herpes simplex virus type 1 (HSV-1) within the unique
      long (UL) region, and it is most similar at the amino acid level to MDV2,
      herpesvirus of turkeys (HVT), and nonavian herpesviruses equine herpesviruses 1
      and 4. MDV1 encodes 55 HSV-1 UL homologues together with 6 additional UL proteins
      that are absent in nonavian herpesviruses. The unique short (US) region is
      colinear with and has greater than 99% nucleotide identity to that of MDV1 strain
      GA; however, an extra nucleotide sequence at the Md5 US/short terminal repeat
      boundary results in a shorter US region and the presence of a second gene
      (encoding MDV097) similar to the SORF2 gene. MD5, like HVT, encodes an ICP4
      homologue that contains a 900-amino-acid amino-terminal extension not found in
      other herpesviruses. Putative virulence and host range gene products include the
      oncoprotein MEQ, oncogenicity-associated phosphoproteins pp38 and pp24, a lipase
      homologue, a CxC chemokine, and unique proteins of unknown function MDV087 and
      MDV097 (SORF2 homologues) and MDV093 (SORF4). Consistent with its virulent
      phenotype, Md5 contains only two copies of the 132-bp repeat which has previously
      been associated with viral attenuation and loss of oncogenicity.

PMID- 10933708
TI  - Detachment of human immunodeficiency virus type 1 from germinal centers by
      blocking complement receptor type 2.
AB  - After the transition from the acute to the chronic phase of human
      immunodeficiency virus (HIV) infection, complement mediates long-term storage of
      virions in germinal centers (GC) of lymphoid tissue. The contribution of
      particular complement receptors (CRs) to virus trapping in GC was studied on
      tonsillar specimens from HIV-infected individuals. CR2 (CD21) was identified as
      the main binding site for HIV in GC. Monoclonal antibodies (MAb) blocking the CR2
      C3d interaction were shown to detach 62 to 77% of HIV type 1 from tonsillar cells
      of an individual in the presymptomatic stage. Although they did so at a lower
      efficiency, these antibodies were able to remove HIV from tonsillar cells of
      patients under highly active antiretroviral therapy, suggesting that the C3d-CR2
      interaction remains a primary entrapment mechanism in treated patients as well.
      In contrast, removal of HIV was not observed with MAb blocking CR1 or CR3. Thus,
      targeting CR2 may facilitate new approaches toward a reduction of residual virus
      in GC.

PMID- 10933709
TI  - CD40 ligand-dependent activation of cytotoxic T lymphocytes by adeno-associated
      virus vectors in vivo: role of immature dendritic cells.
AB  - Recombinant adeno-associated virus type 2 (rAAV) is being explored as a vector
      for gene therapy because of its broad host range, good safety profile, and
      persistent transgene expression in vivo. However, accumulating evidence indicates
      that administration of AAV vector may initiate a detectable cellular and humoral
      immune response to its transduced neo-antigen in vivo. To elucidate the cellular
      basis of the AAV-mediated immune response, C57BL/6 mouse bone marrow-derived
      immature and mature dendritic cells (DCs) were infected with AAV encoding beta
      galactosidase (AAV-lacZ) and adoptively transferred into mice that had received
      an intramuscular injection of AAV-lacZ 10 days earlier. Unexpectedly, C57BL/6
      mice but not CD40 ligand-deficient (CD40L(-/-)) mice adoptively transferred with
      AAV-lacZ-infected immature DCs developed a beta-galactosidase-specific cytotoxic
      T-lymphocyte (CTL) response that markedly diminished AAV-lacZ-transduced gene
      expression in muscle fibers. In contrast, adoptive transfer of AAV-lacZ-infected
      mature DCs failed to elicit a similar CTL response in vivo. Our findings
      indicate, for the first time, that immature DCs may be able to elicit a CD40L
      dependent T-cell immunity to markedly diminish AAV-lacZ transduced gene
      expression in vivo when a sufficient number of DCs capturing rAAV vector and/or
      its transduced gene products is recruited.

PMID- 10933710
TI  - Identification of immunodominant and conformational epitopes in the capsid
      protein of hepatitis E virus by using monoclonal antibodies.
AB  - Antibody to the capsid (PORF2) protein of hepatitis E virus (HEV) is sufficient
      to confer immunity, but knowledge of B-cell epitopes in the intact capsid is
      limited. A panel of murine monoclonal antibodies (MAbs) was generated following
      immunization with recombinant ORF2.1 protein, representing the C-terminal 267
      amino acids (aa) of the 660-aa capsid protein. Two MAbs reacted exclusively with
      the conformational ORF2.1 epitope (F. Li, J. Torresi, S. A. Locarnini, H. Zhuang,
      W. Zhu, X. Guo, and D. A. Anderson, J. Med. Virol. 52:289-300, 1997), while the
      remaining five demonstrated reactivity with epitopes in the regions aa 394 to
      414, 414 to 434, and 434 to 457. The antigenic structures of both the ORF2.1
      protein expressed in Escherichia coli and the virus-like particles (VLPs)
      expressed using the baculovirus system were examined by competitive enzyme-linked
      immunosorbent assays (ELISAs) using five of these MAbs and HEV patient sera.
      Despite the wide separation of epitopes within the primary sequence, all the MAbs
      demonstrated some degree of cross-inhibition with each other in ORF2. 1 and/or
      VLP ELISAs, suggesting a complex antigenic structure. MAbs specific for the
      conformational ORF2.1 epitope and a linear epitope within aa 434 to 457 blocked
      convalescent patient antibody reactivity against VLPs by approximately 60 and
      35%, respectively, while MAbs against epitopes within aa 394 to 414 and 414 to
      434 were unable to block patient serum reactivity. These results suggest that
      sequences spanning aa 394 to 457 of the capsid protein participate in the
      formation of strongly immunodominant epitopes on the surface of HEV particles
      which may be important in immunity to HEV infection.

PMID- 10933711
TI  - Targeted infection of endothelial cells by avian influenza virus A/FPV/Rostock/34
      (H7N1) in chicken embryos.
AB  - The tissue tropism and spread of infection of the highly pathogenic avian
      influenza virus A/FPV/Rostock/34 (H7N1) (FPV) were analyzed in 11-day-old chicken
      embryos. As shown by in situ hybridization, the virus caused generalized
      infection that was strictly confined to endothelial cells in all organs. Studies
      with reassortants of FPV and the apathogenic avian strain A/chick/Germany/N/49
      (H10N7) revealed that endotheliotropism was linked to FPV hemagglutinin (HA). To
      further analyze the factors determining endotheliotropism, the HA-activating
      protease furin was cloned from chicken tissue. Ubiquitous expression of furin and
      other proprotein convertases in the chick embryo indicated that proteolytic
      activation of HA was not responsible for restriction of infection to the
      endothelium. To determine the expression of virus receptors in embryonic tissues,
      histochemical analysis of alpha2,3- and alpha2,6-linked neuraminic acid was
      carried out by lectin-binding assays. These receptors were found on endothelial
      cells and on several epithelial cells, but not on tissues surrounding endothelia.
      Finally, we analyzed the polarity of virus maturation in endothelial cells.
      Studies on cultured human endothelial cells employing confocal laser scanning
      microscopy revealed that HA is specifically targeted to the apical surface of
      these cells, and electron microscopy of embryonic tissues showed that virus
      maturation occurs also at the luminar side. Taken together, these observations
      indicate that endotheliotropism of FPV in the chicken embryo is determined, on
      one hand, by the high cleavability of HA, which mediates virus entry into the
      vascular system, and, on the other hand, by restricted receptor expression and
      polar budding, which prevent spread of infection into tissues surrounding
      endothelia.

PMID- 10933712
TI  - Role of human cytomegalovirus immediate-early proteins in cell growth control.
AB  - Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that has been implicated
      in several disorders, including an association between HCMV reactivation and the
      overproliferation of arterial smooth muscle cells observed in restenosis.
      Although HCMV can mediate a growth-arrest phenotype in infected cells, the virus
      can also promote an environment conducive to proliferation. Here, we present
      evidence that the HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, may be
      responsible for inducing this proliferative environment by altering cell cycle
      control. We find that expression of either of these IE proteins can alter the
      cell cycle distribution of randomly cycling cells towards S and G(2)/M phases.
      Additionally, we find that expression of IE2-86, but not IE1-72, induces
      quiescent cells into S phase and delays cell cycle exit. In the absence of p53,
      IE1-72 expression can induce S phase and delay cell cycle exit. We also
      demonstrate that p53 protein levels increase in fibroblasts following the
      expression of IE1-72. The observed accumulation of p53 protein in IE1-72
      expressing cells may account for the inability of IE1-72 to induce S phase and
      delay cell cycle exit. Our data suggest that expression of HCMV IE1-72 and IE2-86
      is sufficient to alter the cell cycle to generate an environment conducive to
      proliferation.

PMID- 10933713
TI  - Membrane interface-interacting sequences within the ectodomain of the human
      immunodeficiency virus type 1 envelope glycoprotein: putative role during viral
      fusion.
AB  - We have identified a region within the ectodomain of the fusogenic human
      immunodeficiency virus type 1 (HIV-1) gp41, different from the fusion peptide,
      that interacts strongly with membranes. This conserved sequence, which
      immediately precedes the transmembrane anchor, is not highly hydrophobic
      according to the Kyte-Doolittle hydropathy prediction algorithm, yet it shows a
      high tendency to partition into the membrane interface, as revealed by the Wimley
      White interfacial hydrophobicity scale. We have investigated here the membrane
      effects induced by NH(2)-DKWASLWNWFNITNWLWYIK-CONH(2) (HIV(c)), the membrane
      interface-partitioning region at the C terminus of the gp41 ectodomain, in
      comparison to those caused by NH(2)-AVGIGALFLGFLGAAGSTMGARS-CONH(2) (HIV(n)), the
      fusion peptide at the N terminus of the subunit. Both HIV(c) and HIV(n) were seen
      to induce membrane fusion and permeabilization, although lower doses of HIV(c)
      were required for comparable effects to be detected. Experiments in which
      equimolar mixtures of HIV(c) and HIV(n) were used indicated that both peptides
      may act in a cooperative way. Peptide-membrane and peptide-peptide interactions
      underlying those effects were further confirmed by analyzing the changes in
      fluorescence of peptide Trp residues. Replacement of the first three Trp residues
      by Ala, known to render a defective gp41 phenotype unable to mediate both cell
      cell fusion and virus entry, also abrogated the HIV(c) ability to induce membrane
      fusion or form complexes with HIV(n) but not its ability to associate with
      vesicles. Hydropathy analysis indicated that the presence of two membrane
      partitioning stretches separated by a collapsible intervening sequence is a
      common structural motif among other viral envelope proteins. Moreover, sequences
      with membrane surface-residing residues preceding the transmembrane anchor
      appeared to be a common feature in viral fusion proteins of several virus
      families. According to our experimental results, such a feature might be related
      to their fusogenic function.

PMID- 10933714
TI  - ATP is required for correct folding and disulfide bond formation of rotavirus
      VP7.
AB  - Rotavirus is one of very few viruses that utilize the endoplasmic reticulum (ER)
      for assembly, and therefore it has been used as an attractive model to study ER
      associated protein folding. In this study, we have examined the requirements for
      metabolic energy (ATP) for correct folding of the luminal and ER-associated VP7
      of rotavirus. We found that VP7 rapidly misfolds in an energy-depleted milieu and
      is not degraded within 60 min. We also found that VP7 attained a stable minimum
      energy state soon after translation in the ER. Most surprisingly, energy
      misfolded VP7 could be recovered and establish correct disulfide bonds and
      antigenicity following a shift to an ATP-rich milieu. Using a Semliki Forest
      virus expression system, we observed that VP7 requires ATP and cellular, but not
      viral, factors for correct disulfide bond formation. Our results show for the
      first time that the disulfide bond formation of rotavirus VP7 is an ATP-dependent
      process. It has previously been shown that chaperones hydrolyze ATP during
      interaction with newly synthesized polypeptides and prevent nonproductive intra-
      and intermolecular interactions. The most reasonable explanation for the energy
      requirement of VP7 is thus a close interaction during folding with an ATP
      dependent chaperone, such as BiP (Grp78), and possibly with protein disulfide
      isomerase. Taken together, our observations provide new information about folding
      of ER-associated proteins in general and rotavirus VP7 in particular.

PMID- 10933715
TI  - Functional interaction between pleiotropic transactivator pUL69 of human
      cytomegalovirus and the human homolog of yeast chromatin regulatory protein SPT6.
AB  - The phosphoprotein pUL69 of human cytomegalovirus (HCMV), which is a herpesvirus
      of considerable medical importance in immunosuppressed patients and newborns, has
      previously been identified as an early-late viral protein that can stimulate
      several viral and cellular promoters and thus exerts a rather broad activation
      pattern. To gain insight into the mechanism of this transactivation process, we
      looked for cellular factors interacting with pUL69 in a yeast two-hybrid screen.
      Using a B-lymphocyte cDNA library fused to the GAL4 activation domain, we
      identified 34 clones, 11 of which comprised one distinct gene. Interaction with
      this gene turned out to be very strong, producing beta-galactosidase levels 100
      fold greater than the background as measured in an ONPG (o-nitrophenyl-beta-D
      galactopyranoside) assay. Sequencing identified this gene as the human homolog of
      the yeast factor SPT6, which is thought to be involved in the regulation of
      chromatin structure. A direct interaction of pUL69 and the carboxy terminus of
      hSPT6 could be demonstrated using in vitro pull-down experiments. After having
      generated a specific antiserum that is able to detect the endogenous hSPT6
      protein, we were able to observe an in vivo interaction of both proteins by
      coimmunoprecipitation analysis. The interaction domain within pUL69 was mapped to
      a central domain of this viral protein that is conserved within the homologous
      proteins of other herpesviruses such as the ICP27 protein of herpes simplex
      virus. Internal deletions within this central domain, as well as a single amino
      acid exchange at position C495, resulted in a loss of interaction. This
      correlated with a loss of the transactivation potential of the respective
      mutants, suggesting that the hSPT6 interaction of pUL69 is essential for
      stimulating gene expression. Furthermore, we demonstrate that the carboxy
      terminus of hSPT6 also binds to histon H3 and that this interaction can be
      antagonized by pUL69. This allows the deduction of a model by which pUL69 acts as
      an antirepressor by competing for binding of histones to hSPT6, thereby
      antagonizing the chromatin remodeling function of this cellular protein.

PMID- 10933716
TI  - Molecular cloning and functional analysis of three type D endogenous retroviruses
      of sheep reveal a different cell tropism from that of the highly related
      exogenous jaagsiekte sheep retrovirus.
AB  - Integrated into the sheep genome are 15 to 20 copies of type D endogenous loci
      that are highly related to two exogenous oncogenic viruses, jaagsiekte sheep
      retrovirus (JSRV) and enzootic nasal tumor virus (ENTV). The exogenous viruses
      cause infectious neoplasms of the respiratory tract in small ruminants. In this
      study, we molecularly cloned three intact type D endogenous retroviruses of sheep
      (enJS56A1, enJS5F16, and enJS59A1; collectively called enJRSVs) and analyzed
      their genomic structures, their phylogenies with respect to their exogenous
      counterparts, their capacity to form viral particles, and the expression
      specificities of their long terminal repeats (LTRs). In addition, the pattern of
      expression of enJSRVs in vivo was studied by in situ hybridization. All of the
      three enJSRV proviruses had open reading frames for at least one of the
      structural genes. In particular, enJS56A1 had open reading frames for all
      structural genes, but it could not assemble viral particles when highly expressed
      in human 293T cells. We localized the defect for viral assembly in the first two
      thirds of the gag gene by making a series of chimeras between enJS56A1 and the
      exogenous infectious molecular clone JSRV(21). Phylogenetic analysis
      distinguished five ovine type D retroviruses: enJSRV groups A and B, ENTV, and
      two exogenous JSRV groups (African versus United Kingdom/North America isolates).
      Transient transfection assays indicated that the LTRs of the three enJSRVs were
      not preferentially active in differentiated lung epithelial cells. This suggests
      that the pulmonary tropic JSRV developed from a type D retrovirus that did not
      have lung specificity. Consistent with this, in situ hybridization of a panel of
      normal ovine tissues revealed high expression of enJSRV mRNA in the luminal
      epithelium and glandular epithelium of the uterus; lower expression was localized
      in the lamina propria of the gut and in the bronchiolar epithelium of the lungs.

PMID- 10933717
TI  - Human immunodeficiency virus type 1 induces apoptosis in CD4(+) but not in CD8(+)
      T cells in ex vivo-infected human lymphoid tissue.
AB  - Progression of human immunodeficiency virus (HIV) disease is associated with
      massive death of CD4(+) T cells along with death and/or dysfunction of CD8(+) T
      cells. In vivo, both HIV infection per se and host factors may contribute to the
      death and/or dysfunction of CD4(+) and CD8(+) T cells. Progression of HIV disease
      is often characterized by a switch from R5 to X4 HIV type 1 (HIV-1) variants. In
      human lymphoid tissues ex vivo, it was shown that HIV infection is sufficient for
      CD4(+) T-cell depletion. Here we address the question of whether infection of
      human lymphoid tissue ex vivo with prototypic R5 or X4 HIV variants also depletes
      or impairs CD8(+) T cells. We report that whereas productive infection of
      lymphoid tissue ex vivo with R5 and X4 HIV-1 isolates induced apoptosis in CD4(+)
      T cells, neither viral isolate induced apoptosis in CD8(+) T cells. Moreover, in
      both infected and control tissues we found similar numbers of CD8(+) T cells and
      similar production of cytokines by these cells in response to phorbol myristate
      acetate or anti-CD3-anti-CD28 stimulation. Thus, whereas HIV-1 infection per se
      in human lymphoid tissue is sufficient to trigger apoptosis in CD4(+) T cells,
      the death of CD8(+) T cells apparently requires additional factors.

PMID- 10933718
TI  - Sodium-dependent neutral amino acid transporter type 1 is an auxiliary receptor
      for baboon endogenous retrovirus.
AB  - The baboon endogenous retrovirus (BaEV) belongs to a large, widely dispersed
      interference group that includes the RD114 feline endogenous virus and primate
      type D retroviruses. Recently, we and another laboratory independently cloned a
      human receptor for these viruses and identified it as the human sodium-dependent
      neutral amino acid transporter type 2 (hASCT2). Interestingly, mouse and rat
      cells are efficiently infected by BaEV but only become susceptible to RD114 and
      type D retroviruses if the cells are pretreated with tunicamycin, an inhibitor of
      protein N-linked glycosylation. To investigate this host range difference, we
      cloned and analyzed NIH Swiss mouse ASCT2 (mASCT2). Surprisingly, mASCT2 did not
      mediate BaEV infection, which implied that mouse cells might have an alternative
      receptor for this virus. In addition, elimination of the two N-linked
      oligosaccharides from mASCT2 by mutagenesis, as substantiated by protein N
      glycosidase F digestions and Western immunoblotting, did not enable it to
      function as a receptor for RD114 or type D retroviruses. Based on these results,
      we found that the related ASCT1 transporters of humans and mice are efficient
      receptors for BaEV but are relatively inactive for RD114 and type D retroviruses.
      Furthermore, elimination of the two N-linked oligosaccharides from extracellular
      loop 2 of mASCT1 by mutagenesis enabled it to function as an efficient receptor
      for RD114 and type D retroviruses. Thus, we infer that the tunicamycin-dependent
      infection of mouse cells by RD114 and type D retroviruses is caused by
      deglycosylation of mASCT1, which unmasks previously buried sites for viral
      interactions. In contrast, BaEV efficiently employs the glycosylated forms of
      mASCT1 that occur normally in untreated mouse cells.

PMID- 10933719
TI  - Chimeric yellow fever/dengue virus as a candidate dengue vaccine: quantitation of
      the dengue virus-specific CD8 T-cell response.
AB  - We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which
      expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2)
      virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice
      with this chimeric virus induced a CD8 T-cell response specific for the DEN-2
      virus prM and E proteins. This response protected YF/DEN virus-immunized mice
      against lethal dengue encephalitis. Control mice immunized with the parental YFV
      17D were not protected against DEN-2 virus challenge, indicating that protection
      was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN
      vaccine-primed CD8 T cells expanded and were efficiently recruited into the
      central nervous systems of DEN-2 virus challenged mice. At 5 days after
      challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E
      proteins, and 34% of CD8 T cells in the central nervous system recognized these
      proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the
      protective efficacy of the YF/DEN virus, stressing the key role of the antiviral
      T-cell response.

PMID- 10933720
TI  - The collagen repeat sequence is a determinant of the degree of herpesvirus
      saimiri STP transforming activity.
AB  - Herpesvirus saimiri (HVS) is divided into three subgroups, A, B, and C, based on
      sequence divergence at the left end of genomic DNA in which the saimiri
      transforming protein (STP) resides. Subgroup A and C strains transform primary
      common marmoset lymphocytes to interleukin-2-independent growth, whereas subgroup
      B strains do not. To investigate the nononcogenic phenotype of the subgroup B
      viruses, STP genes from seven subgroup B virus isolates were cloned and
      sequenced. Consistent with the lack of oncogenic activity of HVS subgroup B
      viruses, STP-B was deficient for transforming activity in rodent fibroblast
      cells. Sequence comparison reveals that STP-B lacks the signal-transducing
      modules found in STP proteins of the other subgroups, collagen repeats and an
      authentic SH2 binding motif. Substitution mutations demonstrated that the lack of
      collagen repeats but not an SH2 binding motif contributed to the nontransforming
      phenotype of STP-B. Introduction of the collagen repeat sequence induced
      oligomerization of STP-B, resulting in activation of NF-kappaB activity and
      deregulation of cell growth control. These results demonstrate that the collagen
      repeat sequence is a determinant of the degree of HVS STP transforming activity.

PMID- 10933721
TI  - The 5' RNA terminus of spleen necrosis virus stimulates translation of nonviral
      mRNA.
AB  - The RU5 region at the 5' RNA terminus of spleen necrosis virus (SNV) has been
      shown to facilitate expression of human immunodeficiency virus type 1 (HIV)
      unspliced RNA independently of the Rev-responsive element (RRE) and Rev. The SNV
      sequences act as a distinct posttranscriptional control element to stimulate gag
      RNA nuclear export and association with polyribosomes. Here we sought to
      determine whether RU5 functions to neutralize the cis-acting inhibitory sequences
      (INSs) in HIV RNA that confer RRE/Rev dependence or functions as an independent
      stimulatory sequence. Experiments with HIV gag reporter plasmids that contain
      inactivated INS-1 indicated that neutralization of INSs does not account for RU5
      function. Results with luciferase reporter gene (luc) plasmids further indicated
      that RU5 stimulates expression of a nonretroviral RNA that lacks INSs. Northern
      blot and RT-PCR analyses indicated that RU5 does not increase the steady-state
      levels or nuclear export of the luc transcript but rather that the U5 region
      facilitates efficient polyribosomal association of the mRNA. RU5 does not
      function as an internal ribosome entry site in bicistronic reporter plasmids, and
      it requires the 5'-proximal position for efficient function. Our results indicate
      that RU5 contains stimulatory sequences that function in a 5'-proximal position
      to enhance initiation of translation of a nonretroviral reporter gene RNA. We
      speculate that RU5 evolved to overcome the translation-inhibitory effect of the
      highly structured encapsidation signal and other replication motifs in the 5'
      untranslated region of the retroviral RNA.

PMID- 10933723
TI  - Characterization of the coronavirus M protein and nucleocapsid interaction in
      infected cells.
AB  - Coronavirus contains three envelope proteins, M, E and S, and a nucleocapsid,
      which consists of genomic RNA and N protein, within the viral envelope. We
      studied the macromolecular interactions involved in coronavirus assembly in cells
      infected with a murine coronavirus, mouse hepatitis virus (MHV).
      Coimmunoprecipitation analyses demonstrated an interaction between N protein and
      M protein in infected cells. Pulse-labeling experiments showed that newly
      synthesized, unglycosylated M protein interacted with N protein in a pre-Golgi
      compartment, which is part of the MHV budding site. Coimmunoprecipitation
      analyses further revealed that M protein interacted with only genomic-length MHV
      mRNA, mRNA 1, while N protein interacted with all MHV mRNAs. These data indicated
      that M protein interacted with the nucleocapsid, consisting of N protein and mRNA
      1, in infected cells. The M protein-nucleocapsid interaction occurred in the
      absence of S and E proteins. Intracellular M protein-N protein interaction was
      maintained after removal of viral RNAs by RNase treatment. However, the M protein
      N protein interaction did not occur in cells coexpressing M protein and N protein
      alone. These data indicated that while the M protein-N protein interaction, which
      is independent of viral RNA, occurred in the M protein-nucleocapsid complex, some
      MHV function(s) was necessary for the initiation of M protein-nucleocapsid
      interaction. The M protein-nucleocapsid interaction, which occurred near or at
      the MHV budding site, most probably represented the process of specific packaging
      of the MHV genome into MHV particles.

PMID- 10933722
TI  - Mink cell focus-forming murine leukemia virus infection induces apoptosis of
      thymic lymphocytes.
AB  - In a previous study we identified the subpopulations of thymus cells that were
      infected by the lymphomagenic MCF13 murine leukemia virus (MLV) (F. K. Yoshimura,
      T. Wang, and M. Cankovic, J. Virol. 73:4890-4898, 1999) and observed an effect on
      thymus size by virus infection. In this report we describe our results which
      demonstrate that MCF13 MLV infection of thymuses reduced the number of T
      lymphocytes in this organ. Histological examination showed diffuse lymphocyte
      depletion, which was most striking in the CD4(+) CD8(+) lymphocyte-enriched
      cortical zone. Consistent with this, flow cytometric analysis showed that the
      lymphocytes which were depleted were predominantly the immature CD3(-) CD4(+)
      CD8(+) and CD3(+) CD4(+) CD8(+) cells. A comparison of the percentages of live,
      apoptotic, and dead cells of the gp70(+) and gp70(-) thymic lymphocytes suggested
      that this effect on thymus cellularity is a result of virus infection. Studies of
      the survival of thymic T lymphocytes in culture showed that cells from MCF13 MLV
      inoculated mice underwent greater apoptosis and death than cells from control
      animals. Assays for apoptosis included 7-amino-actinomycin D staining, DNA
      fragmentation, and cleavage of caspase-3 and poly(ADP-ribose) polymerase
      proenzymes. Our results suggest that apoptosis of thymic lymphocytes by virus
      infection is an important step in the early stages of MCF13 MLV tumorigenesis.

PMID- 10933724
TI  - Reovirus-induced apoptosis is mediated by TRAIL.
AB  - Members of the tumor necrosis factor (TNF) receptor superfamily and their
      activating ligands transmit apoptotic signals in a variety of systems. We now
      show that the binding of TNF-related, apoptosis-inducing ligand (TRAIL) to its
      cellular receptors DR5 (TRAILR2) and DR4 (TRAILR1) mediates reovirus-induced
      apoptosis. Anti-TRAIL antibody and soluble TRAIL receptors block reovirus-induced
      apoptosis by preventing TRAIL-receptor binding. In addition, reovirus induces
      both TRAIL release and an increase in the expression of DR5 and DR4 in infected
      cells. Reovirus-induced apoptosis is also blocked following inhibition of the
      death receptor-associated, apoptosis-inducing molecules FADD (for FAS-associated
      death domain) and caspase 8. We propose that reovirus infection promotes
      apoptosis via the expression of DR5 and the release of TRAIL from infected cells.
      Virus-induced regulation of the TRAIL apoptotic pathway defines a novel mechanism
      for virus-induced apoptosis.

PMID- 10933725
TI  - Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8(+)
      T lymphocytes in healthy seropositive donors.
AB  - Human cytomegalovirus (HCMV) infection is largely asymptomatic in the
      immunocompetent host, but remains a major cause of morbidity in immunosuppressed
      individuals. Using the recently described technique of staining antigen-specific
      CD8(+) T cells with peptide-HLA tetrameric complexes, we have demonstrated high
      levels of antigen-specific cells specific for HCMV peptides and show that this
      may exceed 4% of CD8(+) T cells in immunocompetent donors. Moreover, by staining
      with tetramers in combination with antibodies to cell surface markers and
      intracellular cytokines, we demonstrate functional heterogeneity of HCMV-specific
      populations. A substantial proportion of these are effector cytotoxic T
      lymphocytes, as demonstrated by their ability to lyse peptide-pulsed targets in
      "fresh" killing assays. These data suggest that the immune response to HCMV is
      periodically boosted by a low level of HCMV replication and that sustained
      immunological surveillance contributes to the maintenance of host-pathogen
      homeostasis. These observations should improve our understanding of the
      immunobiology of persistent viral infection.

PMID- 10933726
TI  - Moloney murine leukemia virus-induced tumors show altered levels of proapoptotic
      and antiapoptotic proteins.
AB  - Moloney murine leukemia virus (M-MuLV) is a replication-competent, simple
      retrovirus that induces T-cell lymphomas when inoculated into neonatal mice. The
      tumor cells are typically derived from immature T cells. During preleukemic
      times, a marked decrease in thymic size is apparent in M-MuLV-inoculated mice. We
      previously demonstrated that this thymic regression is correlated with enhanced
      levels of thymocyte apoptosis (C. Bonzon and H. Fan, J. Virol. 73:2434-2441,
      1999). In this study, we investigated the apoptotic state of M-MuLV-induced
      tumors. M-MuLV-induced tumors were screened for expression of the apoptotic
      proteins Fas and Bcl-2 by three-color flow cytometric analysis. Single-positive
      (SP; CD4(+) CD8(-) and CD4(-) CD8(+)) tumor cells generally displayed lower cell
      surface expression of Fas than SP thymocytes from uninoculated control mice.
      Double-positive (DP; CD4(+) CD8(+)) M-MuLV-induced tumor cells fell into two
      categories: those with normal high levels of Fas and those with low levels of
      Fas. Additionally, the vast majority of DP tumors showed elevated Bcl-2 levels.
      The DP tumor cells retaining normal/high Fas expression were capable of
      transducing an apoptotic signal upon anti-Fas engagement. In addition, DP and
      CD4(+) SP tumor populations displayed higher levels of Fas ligand than normal
      thymocytes with the same phenotypes. In contrast, CD8(+) SP and CD4(-) CD8(-)
      tumors did not show elevated Fas ligand expression. There was no significant
      correlation between Fas and Fas ligand expression in the DP tumors, suggesting
      that Fas Ligand expression was not the driving force behind Fas down-regulation.
      These results suggest that both the Fas death receptor and mitochondrial pathways
      of apoptotic death are active in M-MuLV-induced tumors and that they must be
      modulated to permit cell survival and tumor outgrowth.

PMID- 10933727
TI  - Human immunodeficiency virus type 1 Vpr contains two leucine-rich helices that
      mediate glucocorticoid receptor coactivation independently of its effects on G(2)
      cell cycle arrest.
AB  - Human immunodeficiency virus type 1 (HIV-1) Vpr participates in nuclear targeting
      of the viral preintegration complex in nondividing cells and induces G(2) cell
      cycle arrest in proliferating cells, which creates an intracellular milieu
      favorable for viral replication. Vpr also activates the transcription of several
      promoters and enhancers by a poorly understood mechanism. Vpr enhances
      glucocorticoid receptor (GR) signaling and may mediate the effects of steroids on
      HIV replication. More specifically, recombinant Vpr can potentiate virion
      production from U937 cells, downregulate NF-kappaB induction, and enhance
      programmed cell death, all effects also mediated by glucocorticoids. Vpr has been
      proposed to act as a GR coactivator, although other studies suggest that these
      enhancing effects are merely a consequence of G(2) cell cycle arrest. We now
      demonstrate that Vpr functions as a GR coactivator and that this activity is
      independent of cell cycle arrest. In addition, we show that the Vpr-induced
      coactivation requires an intact glucocorticoid response element, that it is
      dependent on the presence of hormone and the corresponding receptor, and that it
      is mediated by the two highly conserved leucine-rich domains within Vpr that
      resemble the GR coactivator signature motif.

PMID- 10933729
TI  - Structure of African swine fever virus late promoters: requirement of a TATA
      sequence at the initiation region.
AB  - A number of mutations, including deletions, linker scan substitutions, and point
      mutations, were performed in the promoter of the late African swine fever virus
      (ASFV) gene coding for the capsid protein p72. The consequences of the mutations
      in terms of promoter activity were analyzed by luciferase assays using plasmids
      transfected into infected cells. The results showed that the promoter function is
      contained between nucleotides -36 and +5 relative to the transcription initiation
      site. Moreover, two major essential regions for promoter activity, centered at
      positions -13 and +3, were located along the 41-bp sequence, the latter mapping
      in the transcription start site. Sequence alignment with other ASFV late
      promoters showed homology in the region of transcriptional initiation, where the
      presence of the sequence TATA was observed in most of the promoters. Substitution
      of these four residues in three other late viral promoters strongly reduced their
      respective activities. These results show that cis-acting control elements of
      ASFV p72 gene transcription are restricted to a short sequence of about 40 bp and
      suggest that transcription of late genes is initiated around a TATA sequence that
      would function as an initiator element.

PMID- 10933728
TI  - Regulation of the Epstein-Barr virus C promoter by AUF1 and the cyclic
      AMP/protein kinase A signaling pathway.
AB  - EBNA2 is an Epstein-Barr virus (EBV)-encoded protein that regulates the
      expression of viral and cellular genes required for EBV-driven B-cell
      immortalization. Elucidating the mechanisms by which EBNA2 regulates viral and
      cellular gene expression is necessary to understand EBV-induced B-cell
      immortalization and viral latency in humans. EBNA2 targets to the latency C
      promoter (Cp) through an interaction with the cellular DNA binding protein CBF1
      (RBPJk). The EBNA2 enhancer in Cp also binds another cellular factor, C promoter
      binding factor 2 (CBF2), whose protein product(s) has not yet been identified.
      Within the EBNA2 enhancer in Cp, we have previously identified the DNA sequence
      required for CBF2 binding and also determined that this element is required for
      efficient activation of Cp by EBNA2. In this study, the CBF2 activity was
      biochemically purified and microsequenced. The peptides sequenced were identical
      to the hnRNP protein AUF1. Antibodies against AUF1 but not antibodies to related
      hnRNP proteins reacted with CBF2 in gel mobility shift assays. In addition,
      stimulation of the cellular cyclic AMP (cAMP)/protein kinase A (PKA) signal
      transduction pathway results in an increase in detectable CBF2/AUF1 binding
      activity extracted from stimulated cells. Furthermore, the CBF2 binding site was
      able to confer EBNA2 responsiveness to a heterologous promoter when transfected
      cells were treated with compounds that activate PKA or by cotransfection of
      plasmids expressing a constitutively active catalytic subunit of PKA. EBNA2
      mediated stimulation of the latency Cp is also increased in similar
      cotransfection assays. These results further support an important role for CBF2
      in mediating EBNA2 transactivation; they identify the hnRNP protein AUF1 as a
      major component of CBF2 and are also the first evidence of a cis-acting sequence
      other than a CBF1 binding element that is able to confer responsiveness to EBNA2.

PMID- 10933730
TI  - The mouse mammary tumor virus transcription enhancers for hematopoietic
      progenitor and mammary gland cells share functional elements.
AB  - Expression of mouse mammary tumor virus (MMTV)-encoded superantigens in B
      lymphocytes is required for viral transmission and pathogenesis. We have
      previously established a critical role of an enhancer element within the long
      terminal repeat (LTR) for MMTV sag gene expression in B-lymphoid progenitor
      cells. We now demonstrate enhancer activity of this element in a promyelocytic
      progenitor cell line. We also map the position of the enhancer within the U3
      region of the MMTV LTR and show that the progenitor cell enhancer shares
      functional elements with a previously described mammary gland-specific enhancer.

PMID- 10933731
TI  - Characterization of a replication-defective human immunodeficiency virus type 1
      att site mutant that is blocked after the 3' processing step of retroviral
      integration.
AB  - Two activities of retroviral integrase, 3' processing and DNA strand transfer,
      are required to integrate viral cDNA into a host cell chromosome. Integrase
      activity has been analyzed in vitro using purified protein and recombinant DNA
      substrates that model the U3 and U5 ends of viral cDNA or by using viral
      preintegration complexes (PICs) that form during virus infection. Numerous
      studies have investigated changes in integrase or viral DNA for effects on both
      3' processing and DNA strand transfer activities using purified protein, but
      similar analyses have not been carried out using PICs. Here, we analyzed PICs
      from human immunodeficiency virus type 1 (HIV-1) strain 604del, an integration
      defective mutant lacking 26 bp of U5, and revE1, a revertant of 604del containing
      an additional 19-bp deletion, for levels of 3' processing activity that occurred
      in infected cells and for levels of in vitro DNA strand transfer activity.
      Whereas revE1 supported one-third to one-half of the level of wild-type DNA
      strand transfer activity, the level of 604del DNA strand transfer activity was
      undetectable. Surprisingly, integrase similarly processed the 3' ends of 604del
      and revE1 in vivo. We therefore conclude that 604del is blocked in its ability to
      replicate in cells after the 3' processing step of retroviral integration.
      Whereas Western blotting showed that wild-type, revE1, and 604del PICs contained
      similar levels of integrase protein, Mu-mediated PCR footprinting revealed only
      minimal protein-DNA complex formation at the ends of 604del cDNA. We propose that
      604del is replication defective because proteins important for DNA strand
      transfer activity do not stably associate with this cDNA after in vivo 3'
      processing by integrase.

PMID- 10933732
TI  - Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that
      shows homology to viral and cellular interferon regulatory factors.
AB  - The genome of the human herpesvirus 8 (HHV-8) contains a cluster of open reading
      frames (ORFs) encoding proteins with homology to the cellular transcription
      factors of the interferon regulatory factor (IRF) family. Two of these
      homologues, vIRF-1 and vIRF-2, were previously identified and functionally
      analyzed. In this study, we have characterized a novel gene, designated vIRF-3,
      encoded within the previously predicted ORF K10.5 and our newly identified ORF
      K10. 6. Northern blotting of RNA extracted from BCBL-1 cells with a vIRF-3
      specific probe and reverse transcription-PCR analyses revealed a single
      transcript of 2.2 kb with a splice present in the coding region. The vIRF-3 mRNA
      levels in BCBL-1 cells were increased upon 12-O-tetradecanoylphorbol-13-acetate
      treatment, with kinetics of expression similar to those of the early immediate
      genes. The vIRF-3 ORF encodes a 73-kDa protein with homology to cellular IRF-4
      and HHV-8-encoded vIRF-2 and K11. In transient transfection assays with the
      IFNACAT reporter, vIRF-3 functioned as a dominant-negative mutant of both IRF-3
      and IRF-7 and inhibited virus-mediated transcriptional activity of the IFNA
      promoter. Similarly, the overexpression of vIRF-3 in mouse L929 cells resulted in
      inhibition of virus-mediated synthesis of biologically active interferons. These
      results suggest that by targeting IRF-3 and IRF-7, which play a critical role in
      the activation of alpha/beta interferon (IFN) genes, HHV-8 has evolved a
      mechanism by which it directly subverts the functions of IRFs and down-regulates
      the induction of the IFN genes that are important components of the innate
      immunity.

PMID- 10933733
TI  - A monomeric GTPase-negative MxA mutant with antiviral activity.
AB  - MxA is a large, interferon-induced GTPase with antiviral activity against RNA
      viruses. It forms large oligomers, but whether oligomerization and GTPase
      activity are important for antiviral function is not known. The mutant protein
      MxA(L612K) carries a lysine-for-leucine substitution at position 612 and fails to
      form oligomers. Here we show that monomeric MxA(L612K) lacks detectable GTPase
      activity but is capable of inhibiting Thogoto virus in transiently transfected
      Vero cells or in a Thogoto virus minireplicon system. Likewise, MxA(L612K)
      inhibited vesicular stomatitis virus multiplication. These findings indicate that
      MxA monomers are antivirally active and suggest that GTP hydrolysis may not be
      required for antiviral activity. MxA(L612K) is rapidly degraded in cells, whereas
      wild-type MxA is stable. We propose that high-molecular-weight MxA oligomers
      represent a stable intracellular pool from which active MxA monomers are
      recruited.

PMID- 10933734
TI  - Transfer of specificity for human immunodeficiency virus type 1 into primary
      human T lymphocytes by introduction of T-cell receptor genes.
AB  - The introduction of genes encoding T-cell receptor (TCR) chains specific for
      human immunodeficiency virus into T cells of infected patients represents a means
      to quantitatively and qualitatively improve immunity to the virus. Our results
      demonstrate that the high level of TCR expression required for physiologic
      functioning can be reproducibly achieved with retroviral vectors encoding full
      length unmodified TCR chains under the control of a strong internal constitutive
      phosphoglycerate kinase promoter.

PMID- 10933735
TI  - Sex differences in Seoul virus infection are not related to adult sex steroid
      concentrations in Norway rats.
AB  - Field studies of hantavirus infection in rodents report that a higher percentage
      of infected individuals are males than females. To determine whether males were
      more susceptible to hantavirus infection than females, adult male and female Long
      Evans rats (Rattus norvegicus) were inoculated with doses of Seoul virus ranging
      from 10(-4) to 10(6) PFU. The 50% infective doses (ID(50)) were not significantly
      different for male and female rats (10(0.05) and 10(0.8) PFU, respectively). To
      determine whether sex differences in response to infection were related to
      circulating sex steroid hormones, sex steroid concentrations were manipulated and
      antibody responses and virus shedding were assessed following inoculation with
      the ID(90). Regardless of hormone treatment, males had higher anti-Seoul virus
      immunoglobulin G (IgG) and IgG2a (i.e., Th1) responses than females and IgG1
      (i.e., Th2) responses similar to those of females. Males also shed virus in
      saliva and feces longer than females. Manipulation of sex steroids in adulthood
      did not alter immune responses or virus shedding, suggesting that sex steroids
      may organize adult responses to hantavirus earlier during ontogeny.

PMID- 10933736
TI  - Neurologic and developmental disability after extremely preterm birth. EPICure
      Study Group.
AB  - BACKGROUND AND METHODS: Small studies show that many children born as extremely
      preterm infants have neurologic and developmental disabilities. We evaluated all
      children who were born at 25 or fewer completed weeks of gestation in the United
      Kingdom and Ireland from March through December 1995 at the time when they
      reached a median age of 30 months. Each child underwent a formal assessment by an
      independent examiner. Development was evaluated with use of the Bayley Scales of
      Infant Development, and neurologic function was assessed by a standardized
      examination. Disability and severe disability were defined by predetermined
      criteria. RESULTS: At a median age of 30 months, corrected for gestational age,
      283 (92 percent) of the 308 surviving children were formally assessed. The mean
      (+/-SD) scores on the Bayley Mental and Psychomotor Developmental Indexes,
      referenced to a population mean of 100, were 84+/-12 and 87+/-13, respectively.
      Fifty-three children (19 percent) had severely delayed development (with scores
      more than 3 SD below the mean), and a further 32 children (11 percent) had scores
      from 2 SD to 3 SD below the mean. Twenty-eight children (10 percent) had severe
      neuromotor disability, 7 (2 percent) were blind or perceived light only, and 8 (3
      percent) had hearing loss that was uncorrectable or required aids. Overall, 138
      children had disability (49 percent; 95 percent confidence interval, 43 to 55
      percent), including 64 who met the criteria for severe disability (23 percent; 95
      percent confidence interval, 18 to 28 percent). When data from 17 assessments by
      local pediatricians were included, 155 of the 314 infants discharged (49 percent)
      had no disability. CONCLUSIONS: Severe disability is common among children born
      as extremely preterm infants.

PMID- 10933737
TI  - Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with
      tissue plasminogen activator in acute myocardial infarction. Stent versus
      Thrombolysis for Occluded Coronary Arteries in Patients with Acute Myocardial
      Infarction Study Investigators.
AB  - BACKGROUND: Prevention of myocardial damage is the main goal of all reperfusion
      therapies in patients with acute myocardial infarction. The relative efficacy of
      various reperfusion strategies is under intensive investigation. We assessed
      whether coronary stenting combined with the blockade of platelet glycoprotein
      IIb/IIIa receptors produces a greater degree of myocardial salvage than
      fibrinolysis with an accelerated infusion of alteplase, a tissue plasminogen
      activator, in patients with acute myocardial infarction. METHODS: A total of 140
      patients were enrolled in the randomized trial; 71 were assigned to receive a
      stent plus abciximab, and 69 to receive intravenous alteplase. The primary end
      point was the degree of myocardial salvage, determined by means of serial
      scintigraphic studies with technetium Tc 99m sestamibi. The secondary end point
      was a composite of death, reinfarction, and stroke within six months after
      randomization. RESULTS: In the group that received a stent plus abciximab, the
      median size of the final infarct was 14.3 percent of the left ventricle (25th and
      75th percentiles, 6.8 and 24.5 percent), as compared with a median of 19.4
      percent (25th and 75th percentiles, 7.9 and 34.2 percent) in the alteplase group
      (P=0.02). This difference was due to the larger salvage index (the percentage of
      the left ventricle that was salvaged, divided by the percentage that was
      compromised by the initial perfusion defect) in the stent group: 0.57 (25th and
      75th percentiles, 0.35 and 0.69), as compared with 0.26 (25th and 75th
      percentiles, 0.09 and 0.61; P<0.001). The cumulative incidence of death,
      reinfarction, or stroke at six months was lower in the stent group than in the
      alteplase group (8.5 vs. 23.2 percent. P=0.02; relative risk, 0.34; 95 percent
      confidence interval, 0.13 to 0.88). CONCLUSIONS: In patients with acute
      myocardial infarction, coronary stenting plus abciximab leads to a greater degree
      of myocardial salvage and a better clinical outcome than does fibrinolysis with a
      tissue plasminogen activator.

PMID- 10933738
TI  - A comparison of suture repair with mesh repair for incisional hernia.
AB  - BACKGROUND: Incisional hernia is an important complication of abdominal surgery.
      Procedures for the repair of these hernias with sutures and with mesh have been
      reported, but there is no consensus about which type of procedure is best.
      METHODS: Between March 1992 and February 1998, we performed a multicenter trial
      in which we randomly assigned to suture repair or mesh repair 200 patients who
      were scheduled to undergo repair of a primary hernia or a first recurrence of
      hernia at the site of a vertical midline incision of the abdomen of less than 6
      cm in length or width. The patients were followed up by physical examination at
      1, 6, 12, 18, 24, and 36 months. Recurrence rates and potential risk factors for
      recurrent incisional hernia were analyzed with the use of life-table methods.
      RESULTS: Among the 154 patients with primary hernias and the 27 patients with
      first-time recurrent hernias who were eligible for the study, 56 had recurrences
      during the follow-up period. The three-year cumulative rates of recurrence among
      patients who had suture repair and those who had mesh repair were 43 percent and
      24 percent, respectively, with repair of a primary hernia (P=0.02; difference, 19
      percentage points; 95 percent confidence interval, 3 to 35 percentage points).
      The recurrence rates were 58 percent and 20 percent with repair of a first
      recurrence of hernia (P=0.10; difference, 38 percentage points; 95 percent
      confidence interval, -1 to 78 percentage points). The risk factors for recurrence
      were suture repair, infection, prostatism (in men), and previous surgery for
      abdominal aortic aneurysm. The size of the hernia did not affect the rate of
      recurrence. CONCLUSIONS: Among patients with midline abdominal incisional
      hernias, mesh repair is superior to suture repair with regard to the recurrence
      of hernia, regardless of the size of the hernia.

PMID- 10933739
TI  - Separation of conjoined twins with the twin reversed-arterial-perfusion sequence
      after prenatal planning with three-dimensional modeling.

PMID- 10933740
TI  - Strategies for making more organs available for transplantation.

PMID- 10933741
TI  - Islet amyloid and type 2 diabetes mellitus.

PMID- 10933742
TI  - Case records of the Massachusetts General Hospital. Weekly clinicopathological
      exercises. Case 24-2000. A 23-year-old man with seizures and a lesion in the left
      temporal lobe.

PMID- 10933743
TI  - Extremely preterm birth--defining the limits of hope.

PMID- 10933744
TI  - Organ donation by unrelated donors.

PMID- 10933745
TI  - Nondirected donation of kidneys from living donors.

PMID- 10933746
TI  - Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery
      Foundation, Inc., Washington, DC, September 24-27, 2000. 2000 Official Program.

PMID- 10933747
TI  - Reduction of neuronal damage in ischemic stroke using a combination therapy of
      TMB-8 with L-arginine.
AB  - Treatment with a combination of a calcium antagonist TMB-8 and NO donors, L
      arginine and N alpha-benzoyl-L-arginine ethyl ester (BAEE) to prevent
      experimental ischemic stroke were studied in rats through the permanent occlusion
      of the middle cerebral artery and common carotid artery for 60 minutes. When the
      animals were treated with TMB-8, L-arginine, BAEE or NO synthetase inhibitor,
      nitro-L-arginine at time 0 of ischemia, the areas of neuronal necrosis were
      reduced by 98%, 99%, 99% and 89%, respectively. When these compounds were
      administered at 6 hrs after ischemia, the areas of neuronal necrosis were reduced
      by 91%, 96%, 86% and 81%, respectively. When TMB-8, L-arginine, BAEE or nitro-L
      arginine were administered at 24 hours after ischemia, the necrosis areas were
      reduced less effectively by 80%, 89%, 77% and 60%, respectively. A combination
      with TMB-8 and L-arginine at time 0, 6 or 24 hr after ischemia resulted in the
      areas of necrosis being reduced by 99%, 99%, and 89%, respectively. Treatment
      with the combination of TMB-8 and BAEE at time 0, 6 or 24 hrs after ischemia,
      resulted in the areas of necrosis being reduced by 99%, 96%, and 82%,
      respectively. When the drugs were administered at 0 hr of ischemia, L-arginine,
      BAEE and nitro-L-arginine increased NO synthase activity in the ischemic cortex
      from 369 +/- 27 of ischemic control to 614 +/- 39, 511 +/- 32 and 406 +/- 16
      respectively 1 days after stroke. TMB-8 was a potent agent in reducing
      intracellular calcium from the base line and blocking the elevation of calcium
      induced by KCl. The spectrin proteolysis protein, a calcium-activated proteolysis
      protein was also inhibited by TMB-8 in the ischemic cortex. These results
      indicated that a combination of TMB-8 and L-arginine is more effective in
      treating ischemic stroke by simultaneously reducing calcium-activated proteolysis
      and improving of cerebral blood flow than using TMB-8 or L-arginine alone.

PMID- 10933748
TI  - Mutagenesis and expression of the E3-19k lumenal domain of adenovirus type 2.
AB  - CD8+ T cells recognize viral or tumor antigens of 8-10 residues derived from
      cytosolic proteins that are bound to the class I molecules of the major
      histocompatibility complex (MHC). To escape this immune surveillance, adenovirus
      expresses a protein, E3-19k, that specifically down-regulates the cell surface
      expression of class I MHC molecules on infected cells. To most effectively
      manipulate the T-cell response to virus-infected cells, it is essential to
      understand the mechanism by which viruses, such as adenoviruses, down-regulate
      the class I MHC function. We have subcloned the lumenal domain of adenovirus E3
      19k protein in order to characterize its interactions with the class I MHC
      molecules. Several point mutations have also been generated on the E3-19k lumenal
      domain with either the first 96 or 108 amino acids. Attempts to crystallize the
      complexes between E3-19k and class I MHC molecule had been initiated.

PMID- 10933749
TI  - Effect of acarbose administration on plasma concentrations of zinc and copper in
      patients with NIDDM.
AB  - Acarbose reduces the intestinal absorption of dietary carbohydrate, thereby
      ameliorating postprandial hyperglycemia in diabetes mellitus. Dietary
      carbohydrate can modulate the bioavailability of some trace minerals like zinc
      and copper. Deficiencies in these minerals are associated with glucose
      intolerance. It is still unknown whether acarbose's reduction of intestinal
      carbohydrate absorption causes the short supply of these minerals. Thus, we
      investigated the changes in plasma zinc and copper levels in patients with NIDDM,
      after administration of acarbose for 3 months. The results showed that acarbose
      did not significantly affect fasting and postprandial plasma levels of these
      minerals, even after acarbose withdrawal. This study indicated that acarbose
      administration in NIDDM patients over a 3-month period does not influence plasma
      levels of zinc or copper.

PMID- 10933750
TI  - Greater tuberosity osteotomy for treatment of impinge rotator cuff tear.
AB  - Forty-two consecutive patients in whom an impingement of rotator cuff tear had
      been treated with greater tuberosity osteotomy and repair were evaluated by
      relief of pain, return of range of motion and strength of shoulder. The oriental
      acromion is thin and easy to break during the traditional acromioplasty
      procedures. When the decompression is achieved by osteotomy on the greater
      tuberosity which is the common location of cuff tear, not only is adequate
      decompression achieved but also the coracoacromial ligament is preserved.
      Comparison of the results of greater tuberosity osteotomy with those of previous
      acromioplasty studies shows they are mostly similar. At present, these techniques
      can be recommended for use by Chinese orthopaedic surgeons who have to deal with
      the typical oriental bony structures.

PMID- 10933751
TI  - Applicability of BSID-II in diagnosing developmental delay at Kaohsiung area.
AB  - The purpose of this study was to investigate the applicability of BSID-II in
      diagnosing children with developmental delay in Kaohsuing area. Five hundred and
      forty-four children, all who were patients of Developmental Delay Clinic of
      Kaohsuing Medical University, participated in this study. The instrument of this
      study was the Bayley Scales of Infant Development--second edition (BSID-II), the
      primary value of which was in diagnosing developmental delay and planning
      intervention strategies. The standardization and statistical properties of BSID
      II made it one of the best measures of infant development available. The findings
      as follows: (1) the alpha coefficients were between .95 and .99, which were
      higher than data on manual of BSID-II; (2) the reproducibilities, which were
      different with each examiner, were between .9503 and .9633, that were good enough
      to be a developmental scale; (3) Standard Errors of Measurement were between
      2.8589 and 3.8206. It was a restricted sample so that these also were lower than
      the data on manual of BSID-II. This evidence shows BSID-II is a highly reliable
      instrument of developmental assessment at Kaohsuing area. A special norm for
      developmentally delayed children and quality control of examiners are suggested.

PMID- 10933752
TI  - Pituitary tumor cosecreting thyrotropin and prolactin causing hyperthyroidism--a
      case report.
AB  - We report a case of a pituitary tumor cosecreting thyrotropin and prolactin with
      clinical manifestation of thyrotoxicosis, which is a very rare clinical disorder.
      Octreotide therapy is effective in suppressing the secretion of thyrotropin,
      prolactin, and thyroid hormones, and by this, renders relief of symptoms and
      complications of thyrotoxicosis.

PMID- 10933753
TI  - Coexistent insulin dependent diabetes mellitus and hyperthyroidism in a patient
      with Down's syndrome.
AB  - The prevalence of thyroid disease is increased in Down's syndrome. Compared with
      adults, thyroid dysfunction in children with Down's syndrome is less frequently
      reported. Insulin dependent diabetes mellitus is also uncommon in Down's syndrome
      children. Coexistent insulin dependent diabetes mellitus and hyperthyroidism in
      Down's syndrome was only reported once previously in literature. We report an 8
      year-old girl with Down's syndrome that had polyuria, polydipsia, abdominal pain
      and urinary incontinence one and half a month prior to admission. Physical
      examination revealed typical face of Mongolism and tachycardia. Thyroid glands
      were not palpable. Laboratory data revealed diabetic ketoacidosis with plasma
      glucose: 860 mg/dl. She had thyroid hyperfunction with TSH: < 0.1 microU/ml, T3:
      219.7 ng/dl, T4: 15 micrograms/dl. Thyroid autoimmune antibodies were also
      increased. There was markedly increased radiotracer uptake in the bilateral
      thyroid glands in Tc-99 thyroid scan. We suggest that Down's syndrome children
      with insulin dependent diabetes mellitus should be evaluated carefully for
      thyroid function and autoimmune disease.

PMID- 10933754
TI  - Open total talar dislocation--report of two cases.
AB  - Total dislocation of talus from all its surrounding joints (tibiotalar, subtalar
      and talonavicular) is an extremely rare injury. Because of its rarity, only few
      case reports can be found in the literature. In the review of the literature,
      infection and AVN are the most commonly encountered complications that affect the
      outcome of these severe injuries. Herein we report two cases of open total talar
      dislocation. Immediate debridement, reduction of the talus, and primary skin
      closure was done followed by cast immobilization. After more than 2 years follow
      up, neither infection nor AVN was found. We conclude that reimplantation of the
      talus is preferable if the wound is relatively clean. Talectomy, or combined with
      tibiocalcaneal fusion should be reserved for later salvage procedure.

PMID- 10933755
TI  - Concentration dependency of rat blood: air partition coefficients of some
      volatile organic chemicals.
AB  - The rat blood:air partition coefficient (PC) of lipophilic volatile organic
      chemicals (VOCs) cannot be predicted with the sole consideration of their
      solubility in blood water and lipids, suggesting an important role of blood
      proteins. The possible concentration dependency and the quantitative nature of
      VOC binding to blood proteins [i.e., association constant (Ka), number of binding
      sites (n)] have not been investigated previously. The objectives of this study
      were therefore (1) to determine the concentration dependency of the blood:air PC
      (P(b:a)) of four VOCs, bromoform (BF), chloroform (CF), chlorobenzene (CB), and
      ethylbenzene (EB), hypothesized to display binding to rat blood proteins; and (2)
      to derive Ka and n values for these chemicals in rat blood. In vitro studies were
      conducted using 0.1-0.5 ml whole blood, or an equivalent mixture of water and n
      octanol exposed to varying amounts of VOCs (BF, 0.11-11.4 micromol; CB, 0.11-24.6
      micromol; CF, 0.11-186.6 micromol; and EB, 0.11-20.2 micromol) in sealed glass
      vials. The P(b:a) of CB, CF, and EB decreased significantly at higher amounts
      added, with no significant change in their n-octanol + water mixture:air PC. For
      each in vitro exposure situation, the concentration of free chemical (Cfree) in
      rat blood was calculated with the PC for the n-octanol + water mixture, whereas
      the concentration of bound plus free chemical (Ctot) was calculated from
      knowledge of the PC determined experimentally with whole blood. The respective
      values of Ka and n for hemoglobin binding estimated by linear regression of a
      plot of the reciprocal of the molar ratio of bound chemical versus 1/Cfree were:
      BF, 0.8, 4; CB, 2.8, 1.4; CF, 1.8, 1.2; and EB, 2, 1.4. The results of this study
      suggest that the concentration-dependent nature of P(b:a) need not be considered
      for modeling rat inhalation exposures to these VOCs for up to several thousand
      parts per million.

PMID- 10933756
TI  - In vivo cytokine production and resistance to infection after acute exposure to
      3,4-dichloropropionaniline.
AB  - 3,4-Dichloropropionaniline (propanil) is an extensively used postemergent
      herbicide that has been shown to produce toxic and immunotoxic effects. The
      present report examined if acute exposure to propanil altered in vitro or in vivo
      cytokine production in response to antigenic stimulation. Studies to determine
      resistance to infection by the intracellular bacterium Listeria monocytogenes
      after exposure to propanil were also conducted. Our experiments demonstrate that
      in vivo exposure to propanil during bacterial infection reduced the subsequent in
      vitro production of interferon-gamma (IFN-gamma) by splenocytes and liver
      nonparenchymal cells in response to antigenic and mitogenic stimulation.
      Additional experiments examined the production of cytokines in vivo after
      propanil exposure alone or combined propanil exposure and L. monocytogenes
      infection. It was found that the endogenous levels of cytokines in the liver,
      spleen, and blood were similar in control and propanil-treated mice. The levels
      of cytokines were also similar in control and exposed mice that were infected
      with L. monocytogenes. Initial resistance to the infection was not affected by
      exposure to propanil. These results demonstrate that in vivo exposure to propanil
      during a bacterial infection suppresses the subsequent in vitro production of
      cytokines but that the endogenous levels are not affected during the initial
      stages of infection.

PMID- 10933757
TI  - Estradiol and pesticide methoxychlor do not exhibit additivity or synergism in
      the reproductive tract of adult ovariectomized mice.
AB  - The pesticide methoxychlor (MXC) is a DDT substitute that exhibits estrogenic
      activities in different animals. To determine whether there is synergism between
      purified MXC and a natural estrogen, ovariectomized adult mice received 3 daily
      intraperitoneal doses of either 2.5 or 25 ng estradiol-17beta or 0.125, 0.25, or
      0.5 mg MXC administered separately or in combination. The mice were sacrificed on
      d 4. Reproductive tracts were excised, weighed, and one uterine horn was flushed
      with phosphate-buffered saline, with the fluid electrophoresed on a one
      dimensional sodium dodecyl sulfate polyacrylamide gel to determine albumin
      content. The remaining uterine horn and vagina were prepared for histology and
      epithelial height measurements. Estradiol significantly increased reproductive
      tract weights. Although both the vaginal and uterine epithelial heights increased
      in mice treated with combined chemicals when compared to controls, the organ
      histology did not show increased stimulation. Albumin content was significantly
      elevated only in the estradiol group. The present data do not suggest that either
      synergism or additive effects occurred between an estrogen and MXC in the
      reproductive tracts of ovariectomized adult mice. In fact, combining MXC with
      estradiol suggests inhibitory effects.

PMID- 10933759
TI  - Maximizing liver transplantation from non-heart-beating donors.
AB  - In order to increase the supply of transplantable organs, an increasing number of
      organ procurement organizations are adopting policies regarding donations from
      non-heart-beating donors. Few centers, however, actually recover and transplant
      these organs. This article reviews a case in which kidneys and livers imported
      from out of state were successfully recovered from a non-heart-beating donor and
      transplanted. In addition, the article demonstrates how cooperation and
      flexibility in transplant personnel can increase the number of organs
      transplanted from a non-heart-beating donor.

PMID- 10933758
TI  - In vitro studies of cellular and molecular developmental toxicity of adjuvants,
      herbicides, and fungicides commonly used in Red River Valley, Minnesota.
AB  - Recent epidemiologic studies showed increased frequency of birth defects in
      pesticide applicators and general population of the Red River Valley, Minnesota.
      These studies further indicated that this crop growing area used more
      chlorophenoxy herbicides and fungicides than elsewhere in Minnesota. Based on
      frequency of use and known biology, certain herbicides, pesticide additives,
      fungicides, and mycotoxins are suspect agents. To define whether these agents
      affect developmental endpoints in vitro, 16 selected agrochemicals were examined
      using the MCF-7 breast cancer cell line. In the flow cytometric assay, cell
      proliferation in this estrogen-responsive cell line indicates xenobiotic-mediated
      estrogenic effects. Cell viability, morphology, ploidy, and apoptosis were
      incorporated in this assay. Data showed that the adjuvants X-77 and Activate Plus
      induced significant cell proliferation at 0.1 and 1 microg/ml. The commercial
      grade herbicides 2,4-D LV4 and 2,4-D amine induced cell proliferation at 1 and 10
      microg/ml. The reagent-grade 2,4-D products failed to induce proliferation over
      the same concentration range, suggesting that other ingredients in the commercial
      products, presumably adjuvants, could be a factor in these results. The
      fungicides triphenyltin and mancozeb induced apoptosis at concentrations of 4.1
      microg/ml (10(-5) M) and 50 microg/ml, respectively. Triphenyltin also induced
      aneuploidy (C2/M arrest) at 0.41 microg/ml (10(-6) M). Data provide a mechanistic
      step to understanding human reproductive and developmental effects in populations
      exposed to these agrochemicals, and initiative to focusing limited resources for
      future in vivo animal developmental toxicity studies.

PMID- 10933760
TI  - Family adaptation to a child's transplant: pretransplant phase.
AB  - The purpose of this study was to explore the relationship between family stress,
      family coping, social support, perception of stress, and family adaptation from
      the mother's perspective during the pretransplant period in the context of the
      Double ABC-X Model of Family Adaptation. The process of seeking a transplant for
      a child is very stressful, and before interventions can be developed, clinicians
      need to understand how aspects of family life are affected. Twenty-nine mothers
      whose children were being evaluated for a liver transplant constituted the sample
      for this exploratory study. Higher family strains, fewer coping skills, and
      higher perception of stress were related to more unhealthy family adaptation
      during the pre-transplant phase. Data point to the need for close evaluation not
      only for the child's needs but for the family's needs as the family begins the
      process of seeking a transplant for the child.

PMID- 10933761
TI  - Abnormalities in fluids, electrolytes, and metabolism of organ donors.
AB  - Abnormal serum concentrations of electrolytes, hormones, and glucose are common
      throughout donor care. The organ procurement coordinator must properly interpret
      and plan treatment for these changes to prevent intracellular dysfunction in
      donor organs. This article describes abnormalities in magnesium, phosphorous,
      calcium, sodium, potassium, and glucose levels; polyuria; and thyroid and
      pituitary changes. Their potential consequences are discussed, and
      recommendations for treatment options are presented.

PMID- 10933762
TI  - Maintaining acid-base balance in organ donors.
AB  - An abnormal blood pH may cause the loss of donor organs through harmful
      physiological consequences. The organ procurement coordinator must correctly
      analyze the acid-base abnormality and treat its cause while normalizing the blood
      pH. We recommend that treatment of acidemia or alkalemia be first directed toward
      changing parameters on the mechanical ventilator, using the Paco2 to modify blood
      pH. Thereafter, hydrochloric acid or sodium bicarbonate may be administered to
      correct the calculated metabolic acid-base deficit. The types of acidosis or
      alkalosis, dead space effect during mechanical ventilation, base excess, base
      deficit, and the appropriate evaluation of blood lactate are also discussed as
      related to the correction of the acid-base status throughout donor care.

PMID- 10933763
TI  - Japanese organ transplant law: a historical perspective.
AB  - Although organ transplantation following brain death has progressed in the West,
      it has lagged far behind in Japan, following the first such case in 1968. As
      effective immunosuppressants made transplantation a better option, Japanese
      patients increasingly sought treatment overseas. Japanese physician groups
      studied issues related to transplantation but did not succeed in making brain
      dead donor transplants available to patients, and the matter was referred to the
      government. However, transplant medicine was still marked by controversy, and as
      political pressure was applied the controversy deepened, splintering public
      opinion. At the same time, transplant groups continued working to establish
      structures to allow transplantation to proceed. Public awareness and knowledge of
      brain death grew, and acceptance widened. Eventually, legislation was passed in
      June 1997 that allowed organ donations from some brain-dead donors. The law is
      restrictive, and such organ transplants in Japan are still limited.

PMID- 10933764
TI  - Pregnancy in lung transplant recipients.
AB  - Eight female lung transplant recipients, all of whom became pregnant after
      transplant, were reported to the National Transplantation Pregnancy Registry from
      US transplant centers. Outcomes of the 8 pregnancies were 4 live births, 3
      therapeutic abortions, and 1 spontaneous abortion. Three of the 4 newborns were
      premature, with low birth weight (< 2500 grams). Rejection during pregnancy
      occurred in 3 pregnancies (38%). All 8 transplant recipients reported at least 1
      complication during pregnancy, including shortness of breath, rejection, and
      infection. Two of the 4 deliveries were by cesarean section. At follow-up, all
      children were developing well with no residual problems. Female lung transplant
      recipients may face higher risks during pregnancy than other solid organ
      transplant recipients.

PMID- 10933765
TI  - Factors associated with adherence to treatment regimens after lung
      transplantation.
AB  - CONTEXT: The number of patients currently awaiting lung transplantation far
      exceeds the supply of available organs. Adherence to postoperative treatment
      regimens is essential for optimal posttransplant success. OBJECTIVE: The present
      study was designed to examine the demographic and psychological factors
      associated with compliance in patients who have had lung transplants. DESIGN:
      Eighteen women and 13 men participated in this study an average of 24 months
      after transplantation, completing a demographic form, a self-report compliance
      measure, a social support questionnaire, and the Multidimensional Health Locus of
      Control Scale. A significant other or family member and the posttransplant nurse
      coordinator also rated each subject's compliance with the posttransplant regimen.
      RESULTS: Although patients rated themselves as being compliant with aspects of
      their self-care, on more subtle measures of compliance, their self-reported
      compliance was not as impressive. Patients who had had their transplants more
      recently appeared to be more compliant. Patients with cystic fibrosis used their
      spirometer more often than patients with other lung diseases. Family support was
      significantly correlated with self-reported compliance. CONCLUSIONS: This study
      suggests that how patients are asked about adherence to treatment regimens
      influences how compliant they appear. The data also indicate that the longer
      after transplant, the less compliant the patient, and suggests the need for
      patient reeducation at some point after transplant. Longitudinal studies are
      needed to assess the degree to which compliance affects the number of rejection
      and febrile episodes as well as patient mortality after lung transplant.

PMID- 10933766
TI  - Reducing transplant evaluation costs by early identification of unsuitable
      patients.
AB  - Many patients undergo a full transplant evaluation and are rejected for
      transplant on the basis of the test results. Some of these patients could be
      identified earlier in the evaluation process, thus reducing the cost of
      undergoing a full evaluation. Subjects in this study were 117 patients who had
      undergone a heart transplant evaluation over a 6-month period. The rates of
      acceptance, rejection, deferral, and those deferred and later listed were
      monitored: 53% were accepted, 17.1% rejected, 18.8% deferred, and a further 11.1%
      were deferred and then later listed. Of the group that was rejected, 45% were
      rejected on the basis of the cardiopulmonary exercise test and deemed too well
      for transplant. Other reasons for patients being rejected were obesity,
      psychological or social issues, and as a result of other diagnostic testing. The
      transplant evaluation process can be modified so that the cardiopulmonary
      exercise test is performed first, which would reduce the ultimate cost of a
      transplant evaluation from $11,330 to $680. The cardiopulmonary exercise test has
      become an intrinsic part of the cardiac evaluation process and is a strong
      indicator of a patient's suitability for transplant.

PMID- 10933767
TI  - Cataracts, the community and care: are we prepared?

PMID- 10933768
TI  - Operated and unoperated cataract in Australia.
AB  - PURPOSE: To quantify the prevalence of cataract, the outcomes of cataract surgery
      and the factors related to unoperated cataract in Australia. METHODS:
      Participants were recruited from the Visual Impairment Project: a cluster,
      stratified sample of more than 5,000 Victorians aged 40 years and over. At
      examination sites interviews, clinical examinations and lens photography were
      performed. Cataract was defined in participants who had: had previous cataract
      surgery, cortical cataract greater than 4/16, nuclear greater than Wilmer
      standard 2, or posterior subcapsular greater than 1 mm2. RESULTS: The participant
      group comprised 3,271 Melbourne residents, 403 Melbourne nursing home residents
      and 1,473 rural residents. The weighted rate of any cataract in Victoria was
      21.5%. The overall weighted rate of prior cataract surgery was 3.79%. Two hundred
      and forty-nine eyes had had prior cataract surgery. Of these 249 procedures, 49
      (20%) were aphakic, 6 (2.4%) had anterior chamber intraocular lenses and 194
      (78%) had posterior chamber intraocular lenses. Two hundred and eleven of these
      operated eyes (85%) had best-corrected visual acuity of 6/12 or better, the legal
      requirement for a driver's license. Twenty-seven (11%) had visual acuity of less
      than 6/18 (moderate vision impairment). Complications of cataract surgery caused
      reduced vision in four of the 27 eyes (15%), or 1.9% of operated eyes. Three of
      these four eyes had undergone intracapsular cataract extraction and the fourth
      eye had an opaque posterior capsule. No one had bilateral vision impairment as a
      result of cataract surgery. Surprisingly, no particular demographic factors (such
      as age, gender, rural residence, occupation, employment status, health insurance
      status, ethnicity) were related to the presence of unoperated cataract.
      CONCLUSIONS: Although the overall prevalence of cataract is quite high, no
      particular subgroup is systematically underserviced in terms of cataract surgery.
      Overall, the results of cataract surgery are very good, with the majority of eyes
      achieving driving vision following cataract extraction.

PMID- 10933769
TI  - Cataract extraction in a major ophthalmic hospital: day-case or overnight stay?
AB  - PURPOSE: Cataract surgery is increasing in Australia and represents a significant
      burden on limited health resources. This study examines the frequency and
      outcomes of cataract surgery for patients who were hospitalized overnight
      compared with those treated as day surgery cases. METHODS: Medical records of 671
      consecutive admissions for cataract surgery at the Royal Victorian Eye and Ear
      Hospital were reviewed. Data analysed included demographic features, insurance
      status, length of hospitalization, ophthalmic conditions, medical conditions,
      social problems and planned surgical technique. Ophthalmic and anaesthetic
      complications, active ophthalmic and medical interventions were also studied.
      RESULTS: Of the 671 patient admissions for cataract during the study period, 226
      (33.4%) were hospitalized overnight. Factors significantly associated with
      overnight hospitalization in univariate analyses include older age, female sex,
      country residence, Veterans' Affairs insurance, monocular vision status, pre
      existing ischaemic heart disease, pre-existing asthma/chronic obstructive lung
      disease, absence of carer, transportation problems, planned extra-capsular
      cataract extraction technique, ophthalmic complications and active ophthalmic
      and/or medical interventions. After adjusting for possible confounding factors
      using backwards stepwise multivariate logistic regression models all except pre
      existing ischaemic heart disease and ophthalmic complications were significantly
      associated with overnight admission for cataract surgery. In total, 14 cases
      (2.1%) needed active ophthalmic and/or medical interventions, 13 overnight cases
      and one day case. CONCLUSIONS: These data suggest that many patients who are
      hospitalized overnight for cataract surgery could be safely treated as day cases.
      Such a shift in the pattern of care for cataract surgery could provide a
      significant potential for health care savings.

PMID- 10933770
TI  - The New Zealand cataract and refractive surgery survey 1997/1998.
AB  - BACKGROUND: This study documents the current practice for cataract and refractive
      surgery in New Zealand. METHOD: A postal questionnaire was distributed in late
      1997 to all consultant members of the Ophthalmological Society of New Zealand
      that were resident in the country at that time. Most questions were identical to
      the 1997 survey of the American Society of Cataract and Refraction Surgeons
      (ASCRS) to enable a comparison. RESULTS: There were 98 returns from 101 surveys
      distributed. Of the returns, 72 performed cataract surgery, 23 performed PRK and
      11 performed LASIK. ASCRS members did more refractive surgery than did New
      Zealanders: 28 versus 1% of 1-5 RK per month, 7 versus 1% of 1-2 clear lens
      extractions per month and 85 versus 51% had access to an excimer laser. For
      cataract surgery, ASCRS members used more topical anaesthesia (30 vs 5.5%), used
      no sutures more often (73 vs 51%), used more preoperative antibiotics (76 vs 26%)
      and used fewer injections of antibiotic/steroids (38 vs 61%). Otherwise the two
      groups were broadly similar.

PMID- 10933771
TI  - Symptomatic intraocular inflammation in multiple sclerosis.
AB  - PURPOSE: The aim of this study was to determine the type and outcome of uveitis
      in patients with multiple sclerosis. METHODS: A retrospective study of 16
      patients attending the uveitis clinic who had a clinically definite diagnosis of
      multiple sclerosis and symptomatic intraocular inflammation. The type of uveitis
      and complications present as well as the outcome of therapeutic intervention,
      either medical or surgical, was determined. RESULTS: Chronic, bilateral anterior
      uveitis was present in six patients. Secondary cataracts requiring surgery
      occurred in 10 eyes, and trabeculectomy was done on five eyes for secondary
      glaucoma. Symptomatic vitritis (visual blurring and/or visually significant
      floaters) occurred in eight patients and was bilateral in four. Occlusive
      peripheral retinal vasculitis with subsequent areas of ischaemia and
      neovascularization requiring panretinal laser photocoagulation developed in eight
      eyes, five of which also required vitrectomy. Other posterior segment
      complications included macular oedema (four) and epiretinal membrane involving
      the macula (two). Five patients required systemic steroids for control of
      posterior uveitis. The median visual improvement following cataract surgery or
      vitrectomy was 3 Snellen lines to a median visual acuity of 6/18. CONCLUSIONS: A
      wide range of clinical patterns of uveitis, which may be both symptomatic and
      sight-threatening, occur in patients with multiple sclerosis. In addition, the
      complications of uveitis may cause significant visual morbidity, much of which is
      amenable to appropriate surgical intervention. It is important that these
      potentially remediable conditions are recognized and treated to ensure that
      patients with multiple sclerosis retain optimum visual function.

PMID- 10933772
TI  - Intravenous pulse methylprednisolone in the treatment of uveitis associated with
      multiple sclerosis.
AB  - PURPOSE: To demonstrate the safety and effectiveness of intravenous
      methylprednisolone (IVMP) in the treatment of uveitis in association with
      multiple sclerosis (MS). METHODS: Uveitis is an unusual manifestation of MS that
      may be severe, chronic and require systemic immunosuppression therapy. High-dose
      IVMP has previously been shown to be effective in the treatment of inflammatory
      eye disease and MS. Eight episodes of uveitis in five patients with MS were
      treated over a 10-year period in an open, uncontrolled trial. Two patients had
      chronic anterior uveitis, one patient had bilateral panuveitis and two patients
      had intermediate uveitis. RESULTS: All patients responded to IVMP with evidence
      of a decrease in intraocular inflammatory activity and improved visual acuity
      (VA) within 2 weeks of commencing treatment. There were no severe ocular or
      systemic steroid side effects. CONCLUSIONS: Intravenous methylprednisolone is an
      effective, well-tolerated form of therapy for uveitis in patients with MS.

PMID- 10933773
TI  - Management of diabetic retinopathy by Australian ophthalmologists. Working Group
      on Evaluation of the NHMRC Retinopathy Guideline Distribution. National Health
      and Medical Research Council.
AB  - OBJECTIVE: To describe current management practices of diabetic retinopathy used
      by Australian ophthalmologists. SETTING: Two-page self-administered questionnaire
      mailed to 622 ophthalmologists listed with the Royal Australian College of
      Ophthalmologists. METHODS: The survey included questions about practice details
      such as size and location; specialty; current practice with regard to management
      of patients with diabetes; confidence in screening for diabetic retinopathy; and
      a number of patient scenarios related to screening, follow-up and treatment of
      diabetic retinopathy. RESULTS: Of the 577 eligible ophthalmologists, 475 (82%)
      completed the questionnaire. They had been practicing ophthalmology between 1 and
      50 years (median 16 years) and 89 (19%) indicated that they had a subspecialty
      interest either in vitreo-retinal surgery or in medical retina. For 145 (30.5%)
      of the ophthalmologists, at least one of their practices was located in a country
      area. The estimated percentage of patients with diabetes ranged from 0.1 to 60%
      (mean = 9.9%). Retinal specialists perform between 0 and 750 macular focal
      photocoagulation procedures per year (mean = 94) compared with a range of 0-350
      for nonretinal specialists (mean = 10.3) (t = 6.1, P < 0.001). The
      ophthalmologists were presented with a hypothetical patient with cataract
      requiring surgery and clinically significant macular oedema that would be
      difficult to treat (but not impossible) because of the cataract. Seventy-seven
      ophthalmologists (16%) said they would delay the macular laser therapy until
      after the cataract surgery had been performed. In multivariate logistic
      regression models, nonretinal specialists were 4.44 times as likely to perform
      the cataract surgery first (95%CL = 1.57, 12.6) and ophthalmologists who had been
      in practice more than 15 years were 2.50 times as likely to perform cataract
      surgery first (95%CL = 1.47, 4.26). There were other examples of practice that
      differed from the National Health and Medical Research Council (NHMRC) guidelines
      in patient scenarios. The majority of ophthalmologists (60%) expressed a moderate
      or strong need to learn more about the management of diabetic retinopathy.
      DISCUSSION: The variability in the management of diabetic retinopathy by
      Australian ophthalmologists and the desire of ophthalmologists to learn more
      about diabetic retinopathy provide evidence to support the need for the NHMRC
      Guidelines for Diabetic Retinopathy. These data will be used to evaluate changes
      in practice as a result of the implementation of the guidelines.

PMID- 10933774
TI  - Adverse effects of topical antiglaucoma drugs on the ocular surface.
AB  - PURPOSE: This study was designed to determine the effect of long-term
      antiglaucoma topical medication on the ocular surface; measuring basal Schirmer's
      and tear break-up time tests using conjunctival impression cytology. METHODS: The
      ocular surfaces of 30 control subjects (group 1), 24 primary open-angle glaucoma
      patients treated with 0.5% betaxolol hydrochloride (group 2), 27 primary open
      angle glaucoma patients treated with 0.5% timolol maleate (group 3) and 26
      primary open-angle glaucoma patients treated with 0.5% betaxolol and 1%
      dipivefrin hydrochloride (group 4) were evaluated. Basal Schirmer's and tear
      break-up time tests were measured and ocular surface changes were determined by
      impression cytology. Impression cytology specimens of each group were graded and
      scored in the range 0-3 according to Nelson's method. RESULTS: Patients in groups
      2, 3 and 4 showed statistically significant fewer normal basal Schirmer's tests
      (wettability) and tear break-up time tests (P < 0.01). Also, the conjunctival
      impression cytology scores were significantly higher in groups 2, 3 and 4 than in
      group 1 (P < 0.01). CONCLUSIONS: The conclusion was that it is possible that
      conjunctival surface and tear film function change after the long-term use of
      antiglaucoma medication.

PMID- 10933775
TI  - Antimicrobial susceptibility of 19 Australian corneal isolates of Acanthamoeba.
AB  - PURPOSE: To determine the in vitro drug susceptibility of Australian corneal
      isolates of Acanthamoeba and to correlate the results with patient treatment and
      visual outcome. METHODS: Acanthomoeba isolates were obtained from a reference
      laboratory Cyst suspensions were prepared from 19 strains and exposed to 10
      antimicrobial agents for 7 days. The minimum drug concentrations required to
      inhibit excystation were determined. Inhibited cells were then plated out to
      determine minimum cysticidal concentrations. RESULTS: Overall, propamidine proved
      to be the most active anti-Acanthamoeba agent tested. The disinfectant
      polyhexamethylene biguanide, either pure or in Baquacil, was also effective.
      Pentamidine, hexamidine, chlorhexidine and chloroxylenol had intermediate
      activity, while neomycin, amphotericin B and povidone-iodine had poor activity.
      There was no clear relationship between in vitro susceptibility and visual
      outcome. CONCLUSIONS: Propamidine and polyhexamethylene biguanide drops are
      recommended as initial choices for the treatment of Acanthamoeba keratitis. The
      variability in the susceptibility to any one agent suggests that individual
      testing of isolates is necessary to identify the most appropriate treatment. A
      number of factors influence visual outcome in these cases; further studies are
      required to resolve the importance or otherwise of in vitro susceptibility.

PMID- 10933776
TI  - Reversal of floppy eyelid syndrome with treatment of obstructive sleep apnoea.
AB  - PURPOSE: To describe the beneficial effects of treatment of obstructive sleep
      apnoea on the symptoms and signs of floppy eyelid syndrome. METHOD: A case of
      sleep apnoea with associated floppy eyelid syndrome is reported. RESULTS: A 32
      year-old man presented with left floppy eyelid syndrome and a known diagnosis of
      obstructive sleep apnoea. He underwent treatment for 4 years with continuous
      positive airways pressure by mask during sleep and the symptoms and signs of his
      floppy eyelid syndrome disappeared. CONCLUSION: Treatment of obstructive sleep
      apnoea may reverse the changes of floppy eyelid syndrome.

PMID- 10933777
TI  - Neuroretinitis associated with cat scratch disease in a child.

PMID- 10933778
TI  - Characterization of the interaction of phospholipase A(2) with
      phosphatidylcholine-phosphatidylglycerol mixed lipids.
AB  - The first requirement in the hydrolysis of phospholipid bilayers by phospholipase
      A(2) is the interaction of the enzyme with the bilayer surface. The catalytic
      ability of phospholipase A(2) has been shown to be extremely sensitive to the
      topology of the bilayer to which it binds and hydrolyzes. Phospholipid bilayer
      properties and composition such as unsaturation, charge, and the presence of
      reaction products are known regulators of the catalytic activity of phospholipase
      A(2) toward the phospholipids and influences the binding of enzyme to the
      membrane. We show in this paper that the effect of increased anionic lipid
      results in enhanced binding that can be described quantitatively in terms of a
      simple phenomenological model. However, the interaction with anionic lipid does
      not singularly dominate the thermodynamics of binding, nor can the lag phase
      observed in the time course of hydrolysis of large unilamellar vesicles simply be
      the result of limited interaction between the enzyme and the bilayer.
      Furthermore, we show that phospholipase A(2) from Akgistrodon piscivorus
      piscivorus can exist in at least two bilayer-bound states and that the absence of
      a fluorescence change upon mixing the enzyme with lipid bilayers does not
      necessarily indicate the absence of an interaction.

PMID- 10933779
TI  - The effects of polar and/or ionizable residues in the core and flanking regions
      of hydrophobic helices on transmembrane conformation and oligomerization.
AB  - To explore the influence of amino acid composition on the behavior of membrane
      inserted alpha-helices, we examined the behavior of Lys-flanked polyleucyl (pLeu)
      helices containing a single polar/ionizable residue within their hydrophobic
      core. To evaluate the location of the helices within the membrane by
      fluorescence, each contained a Trp residue at the center of the sequence. When
      incorporated into dioleoylphosphatidylcholine (DOPC) model membrane vesicles,
      pLeu helices with or without a single Ser, Asn, Lys, or Asp residue in the
      hydrophobic core maintained a transmembrane state (named the N state) at neutral
      and acidic pH. In this state, the central Trp exhibited highly blue-shifted
      fluorescence, and fluorescence quenching by nitroxide-labeled lipids showed it
      located at the bilayer center. A state in which Trp fluorescence red-shifted by
      several nanometers (named the B state) was observed above pH 10-11. B state
      formation appears to result from deprotonation of the flanking Lys residues.
      Despite the red shift in Trp emission, fluorescence quenching showed that in the
      B state the Trp at most is only slightly shallower than in the N state,
      suggesting the B state also is a transmembrane or near-transmembrane structure.
      The B state is characterized by increased helix oligomerization, as shown by the
      dependence of Trp lambda(max) on the concentration of the peptide within the
      bilayer at high pH. The pLeu peptide with a Asp residue in the core underwent a
      pH-dependent transition at a lower pH than the other peptides (pH 8-9). At high
      pH, it exhibited both a more highly red-shifted fluorescence and shallower Trp
      location than the other peptides. This state (named the S state) did not exhibit
      a concentration-dependent Trp lambda(max). We attribute S state behavior to the
      formation of a charged Asp residue at high pH, and a consequent movement of the
      Asp toward the membrane surface, resulting in the formation of a nontransmembrane
      state. We conclude that a polar or ionizable residue can readily be tolerated in
      a single transmembrane helix, but that the charges on ionizable residues in the
      core and regions flanking the helix significantly modulate the stability of
      transmembrane insertion and/or helix-helix association.

PMID- 10933780
TI  - How does GAP catalyze the GTPase reaction of Ras? A computer simulation study.
AB  - The formation of a complex between p21(ras) and GAP accelerates the GTPase
      reaction of p21(ras) and terminates the signal for cell proliferation. The
      understanding of this rate acceleration is important for the elucidation of the
      role of Ras mutants in tumor formation. In principle there are two main options
      for the origin of the effect of GAP. One is a direct electrostatic interaction
      between the residues of GAP and the transition state of the Ras-GAP complex and
      the other is a GAP-induced shift of the structure of Ras to a configuration that
      increases the stabilization of the transition state. This work examines the
      relative importance of these options by computer simulations of the catalytic
      effect of Ras. The simulations use the empirical valence bond (EVB) method to
      study the GTPase reaction along the alternative associative and dissociative
      paths. This approach reproduces the trend in the overall experimentally observed
      catalytic effect of GAP: the calculated effect is 7 +/- 3 kcal/mol as compared to
      the observed effect of approximately 6.6 kcal/mol. Furthermore, the calculated
      effect of mutating Arg789 to a nonpolar residue is 3-4 kcal/mol as compared to
      the observed effect of 4.5 kcal/mol for the Arg789Ala mutation. It is concluded,
      in agreement with previous proposals, that the effect of Arg789 is associated
      with its direct interaction with the transition state charge distribution.
      However, calculations that use the coordinates of Ras from the Ras-GAP complex
      (referred to here as Ras') reproduce a significant catalytic effect relative to
      the Ras coordinates. This indicates that part of the effect of GAP involves a
      stabilization of a catalytic configuration of Ras. This configuration increases
      the positive electrostatic potential on the beta-phosphate (relative to the
      corresponding situation in the free Ras). In other words, GAP stabilizes the GDP
      bound configuration of Ras relative to that of the GTP-bound conformation. The
      elusive oncogenic effect of mutating Gln61 is also explored. The calculated
      effect of such mutations in the Ras-GAP complex are found to be small, while the
      observed effect is very large (8.7 kcal/mol). Since the Ras is locked in its Ras
      GAP configuration in our simulations, we conclude that the oncogenic effect of
      mutation of Gln61 is indirect and is associated most probably with the structural
      changes of Ras upon forming the Ras-GAP complex. In view of these and the results
      for the Ras' we conclude that GAP activates Ras by both direct electrostatic
      stabilization of the transition state and an indirect allosteric effect that
      stabilizes the GDP-bound form. The present study also explored the feasibility of
      the associative and dissociative mechanism in the GTPase reaction of Ras. It is
      concluded that the reaction is most likely to involve an associative mechanism.

PMID- 10933782
TI  - Photolabeling identifies position 172 of the human AT(1) receptor as a ligand
      contact point: receptor-bound angiotensin II adopts an extended structure.
AB  - An angiotensin II (AngII) peptidic analogue in which the third residue (valine)
      was substituted with the photoreactive p-benzoyl-L-phenylalanine (Bpa) was used
      to identify ligand-binding sites of the human AT(1) receptor. High-affinity
      binding of the analogue, (125)I-[Bpa(3)]AngII, to the AT(1) receptor
      heterologously expressed in COS-7 cells enabled us to efficiently photolabel the
      receptor. Chemical and enzymatic digestions of the (125)I-[Bpa(3)]AngII-AT(1)
      complex were performed, and receptor fragments were analyzed in order to define
      the region of the receptor with which the ligand interacts. Results show that
      CNBr hydrolysis of the photolabeled receptor gave a glycosylated fragment which,
      after PNGase-F digestion, migrated as a 11.4 kDa fragment, circumscribing the
      labeled domain between residues 143-243 of the AT(1) receptor. Digestion of the
      receptor-ligand complex with Endo Lys-C or trypsin followed by PNGase-F treatment
      yielded fragments of 7 and 4 kDa, defining the labeling site of (125)I
      [Bpa(3)]AngII within residues 168-199 of the AT(1) receptor. Photolabeling of
      three mutant receptors in which selected residues adjacent to residue 168 were
      replaced by methionine within the 168-199 fragment (I172M, T175M, and I177M)
      followed by CNBr cleavage revealed that the bound photoligand (125)I
      [Bpa(3)]AngII forms a covalent bond with the side chain of Met(172) of the second
      extracellular loop of the AT(1) receptor. These data coupled with previously
      obtained results enable us to propose a model whereby AngII adopts an extended
      beta-strand conformation when bound to the receptor and would orient itself
      within the binding domain by having its N-terminal portion interacting with the
      second extracellular loop and its C-terminus interacting with residues of the
      seventh transmembrane domain.

PMID- 10933781
TI  - Reversing the substrate specificities of phenylalanine and tyrosine hydroxylase:
      aspartate 425 of tyrosine hydroxylase is essential for L-DOPA formation.
AB  - The catalytic domains of the pterin-dependent enzymes phenylalanine hydroxylase
      and tyrosine hydroxylase are homologous, yet differ in their substrate
      specificities. To probe the structural basis for the differences in specificity,
      seven residues in the active site of phenylalanine hydroxylase whose side chains
      are dissimilar in the two enzymes were mutated to the corresponding residues in
      tyrosine hydroxylase. Analysis of the effects of the mutations on the isolated
      catalytic domain of phenylalanine hydroxylase identified three residues that
      contribute to the ability to hydroxylate tyrosine, His264, Tyr277, and Val379.
      These mutations were incorporated into full-length phenylalanine hydroxylase and
      the complementary mutations into tyrosine hydroxylase. The steady-state kinetic
      parameters of the mutated enzymes showed that the identity of the residue in
      tyrosine hydroxylase at the position corresponding to position 379 of
      phenylalanine hydroxylase is critical for dihydroxyphenylalanine formation. The
      relative specificity of tyrosine hydroxylase for phenylalanine versus tyrosine,
      as measured by the (V/K(phe))/(V/K(tyr)) value, increased by 80000-fold in the
      D425V enzyme. However, mutation of the corresponding valine 379 of phenylalanine
      hydroxylase to aspartate was not sufficient to allow phenylalanine hydroxylase to
      form dihydroxyphenylalanine at rates comparable to that of tyrosine hydroxylase.
      The double mutant V379D/H264Q PheH was the most active at tyrosine hydroxylation,
      showing a 3000-fold decrease in the (V/K(phe))/(V/K(tyr)) value.

PMID- 10933783
TI  - Mechanism of the phenylpyruvate tautomerase activity of macrophage migration
      inhibitory factor: properties of the P1G, P1A, Y95F, and N97A mutants.
AB  - Phenylpyruvate tautomerase (PPT) has been studied periodically since its activity
      was first described over forty years ago. In the last two years, the mechanism of
      PPT has been investigated more extensively because of the discovery that PPT is
      the same protein as the immunoregulatory cytokine known as macrophage migration
      inhibitory factor (MIF). The mechanism of PPT is likely to involve general base
      general acid catalysis. While several lines of evidence implicate Pro-1 as the
      general base, the identity of the general acid remains unknown. Crystal
      structures of MIF with the competitive inhibitor (E)-2-fluoro-p-hydroxycinnamate
      bound in the active site and that of the protein complexed with the enol form of
      a substrate, (p-hydroxyphenyl)pyruvate, suggest that Tyr-95 is the only candidate
      in the vicinity that can function as a general acid catalyst. Although Tyr-95 is
      nearby the bound inhibitor and substrate, it is not within hydrogen bonding
      distance of either ligand. In this study, Tyr-95 was mutated to phenylalanine,
      and the kinetic and structural properties of the Y95F mutant were determined.
      This alteration produces a fully active enzyme, which shows no significant
      structural changes in the active site. The results indicate that Tyr-95 does not
      function as the general acid catalyst in the reaction catalyzed by wild-type PPT.
      The mechanism of PPT was studied further by constructing and characterizing the
      kinetic properties of two mutants of Pro-1 (P1G and P1A) and one mutant of Asn-97
      (N97A). The mutation of Asn-97, a residue implicated in the binding of the
      phenolic hydroxy group of the keto and enol isomers of (p-hydroxyphenyl)pyruvate
      and of (E)-2-fluoro-p-hydroxycinnamate affects only the binding affinity of the
      inhibitor. However, the mutations of Pro-1 have a profound effect on the values
      of k(cat) and k(cat)/K(m) and clearly show that Pro-1 is a critical residue in
      the reaction. The results are discussed in terms of a mechanism in which Pro-1
      functions as both the general acid and the general base catalyst.

PMID- 10933784
TI  - Binding kinetics and ligand specificity for the interactions of the C2B domain of
      synaptogmin II with inositol polyphosphates and phosphoinositides.
AB  - Synaptotagmin II (Syt II) is a key protein in the calcium-dependent exocytosis of
      synaptic vesicles. It contains two domains homologous to the C2 regulatory region
      of protein kinase C. The C2A domain acts as a calcium sensor, while the C2B
      domain has high affinity for inositol polyphosphates (InsP(n)()s) and
      phosphoinositide polyphosphates (PtdInsP(n)()s). We describe the use of a surface
      plasmon resonance biosensor in determining the binding kinetics of the C2B domain
      with InsP(n)() and PtdInsP(n) ligands. Biosensor surfaces were prepared with
      covalently attached Ins(1,4,5)P(3), Ins(1,3,4,5)P(4), and InsP(6) ligands. The
      interactions of bacterially expressed His(6)-tagged C2B and (C2A+C2B) domains of
      Syt II were examined in the presence and absence of competing InsP(n)s and
      PtdInsP(n)s. Both His(6)-C2B and His(6)-(C2A+C2B) exhibited the highest affinity
      for the Ins(1,3,4,5)P(4)-modified surface with a K(D) value of 6 nM. The His(6)
      (C2A+C2B) had a 10-fold lower association rate constant for the InsP(6)-linked
      surface (k(a) = 4.6 x 10(3) M(-1) s(-1)) than for the Ins(1,3,4,5)P(4)-modified
      surface (k(a) = 6.8 x 10(4) M(-1) s(-1)). Two water-soluble phosphoinositides,
      dioctanoyl-PtdIns(3,4,5)P(3) and dioctanoyl-PtdIns(4,5)P(2), were superior to the
      soluble InsP(n)s in displacing binding to the Ins(1,3,4,5)P(4)-modified surface.
      The binding of His(6)-C2B and His(6)-(C2A+C2B) to InsP(n) surfaces did not show
      significant calcium dependence. These data support a model in which the binding
      of the C2B domain of Syt II to PtdInsP(n)s is important for the docking and/or
      fusion of the secretory vesicles to the synaptic plasma membrane.

PMID- 10933785
TI  - Phosphatidylcholine activation of human heart (R)-3-hydroxybutyrate dehydrogenase
      mutants lacking active center sulfhydryls: site-directed mutagenesis of a new
      recombinant fusion protein.
AB  - (R)-3-Hydroxybutyrate dehydrogenase (BDH) is a lipid-requiring mitochondrial
      enzyme with a specific requirement of phosphatidylcholine (PC) for function. A
      plasmid has been constructed to express human heart (HH) BDH in Escherichia coli
      as a hexahistidine-tagged fusion protein (HH-Histag-BDH). A rapid two-step
      affinity purification yields active HH-Histag-BDH (and six mutants) with high
      specific activity ( approximately 130 micromol of NAD(+) reduced.min(-1).mg(-1)).
      HH-Histag-BDH has no activity in the absence of phospholipid and exhibits a
      specific requirement of PC for function. The HH-Histag-BDH-PC complex (and HH-BDH
      derived therefrom by enterokinase cleavage) has apparent Michaelis constants
      (K(m) values) for NAD(+), NADH, (R)-3-hydroxybutyrate (HOB), and acetoacetate
      (AcAc) similar to those for bovine heart or rat liver BDH. A computed structural
      model of HH-BDH predicts the two active center sulfhydryls to be C69 (near the
      adenosine moiety of NAD) and C242. With both sulfhydryls derivatized, BDH has
      minimal activity, but site-directed mutagenesis of C69 and/or C242 now shows that
      neither of these cysteines is required for PC activation or catalysis (the double
      mutant, C69A/C242A, is highly active with essentially normal kinetic parameters).
      Six cysteine mutants each have an increased K(m)(NADH) (2-6-fold) but an
      unchanged K(m)(NAD)+. The C242S and C69A/C242S enzymes (but not the analogous
      C242A mutants nor the C69A or C69S mutants) exhibit approximately 10-fold
      increases in K(m)(HOB) and K(m)(AcAc), reflecting an altered substrate binding
      site. Thus, although C242 (in the C-terminal lipid binding domain of BDH) is
      close to the active site, it appears to be in a hydrophobic environment and only
      indirectly defines the substrate binding site at the catalytic center of BDH.

PMID- 10933786
TI  - Crystal structure and immunoglobulin G binding properties of the human major
      histocompatibility complex-related Fc receptor(,).
AB  - The neonatal Fc receptor (FcRn) performs two distinct but related functions:
      transport of maternal immunoglobulin G (IgG) to pre- or neonatal mammals, thus
      providing passive immunity, and protection of IgG from normal serum protein
      catabolism. FcRn is related to class I MHC proteins but lacks a functional
      peptide binding groove. The crystal structure of human FcRn has been determined
      at 2.7 A resolution and compared to the previously described structure of rat
      FcRn [Burmeister et al. (1994) Nature 372, 336-343] and to the structures of MHC
      and MHC-related proteins. Human FcRn is structurally similar to the rat receptor
      but does not form receptor dimers in the crystals as observed in crystals of rat
      FcRn. The interaction between human FcRn and IgG was characterized by determining
      the binding stoichiometry using equilibrium gel filtration and by deriving
      binding affinities for the different human IgG subclasses using a surface plasmon
      resonance assay. Like rat and mouse FcRn, human FcRn interacts with IgG with a
      2:1 receptor:ligand stoichiometry. The binding of human FcRn to the four human
      IgG subclasses shows subclass and allotype variations but no clear subclass
      affinity differences that correlate with serum half-lives. The structure of human
      FcRn and studies of its ligand binding are relevant to current efforts to use
      FcRn-mediated regulation of IgG half-life in serum to increase the lifetimes of
      antibody-based therapeutics.

PMID- 10933787
TI  - Crystal structure at 2.5 A resolution of zinc-substituted copper amine oxidase of
      Hansenula polymorpha expressed in Escherichia coli.
AB  - Copper amine oxidases (CAOs) catalyze the two-electron oxidation of primary
      amines to aldehydes, utilizing molecular oxygen as a terminal electron acceptor.
      To accomplish this transformation, CAOs utilize two cofactors: a mononuclear
      copper, and a unique redox cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ
      or TOPA quinone). TPQ is derived via posttranslational modification of a specific
      tyrosine residue within the protein itself. In this study, the structure of an
      amine oxidase from Hansenula polymorpha has been solved to 2.5 A resolution, in
      which the precursor tyrosine is unprocessed to TPQ, and the copper site is
      occupied by zinc. Significantly, the precursor tyrosine directly ligands the
      metal, thus providing the closest analogue to date of an intermediate in TPQ
      production. Besides this result, the rearrangement of other active site residues
      (relative to the mature enzyme) proposed to be involved in the binding of
      molecular oxygen may shed light on how CAOs efficiently use their active site to
      carry out both cofactor formation and catalysis.

PMID- 10933788
TI  - The receptor binding conformation of bombyxin is induced by alanine(B15).
AB  - Bombyxin is an insect hormone with an insulin-like structure which affects the
      reduction of stored carbohydrates in the silkworm Bombyx mori. The receptor
      binding surface of bombyxin includes a trough on the interface between the B
      chain helix and the N-terminal A chain helix. Alanine(B15) is located on the edge
      of this feature, whereas the bottom is formed by hydrophobic core residues
      Ile(A2) and Leu(B14). Replacement of alanine(B15) with bulkier residues produces
      a negative steric effect on bombyxin receptor binding; alpha-aminobutyric acid
      reduced the affinity to 6.5%, valine to 1.1%, norvaline to 0.88%, and leucine to
      0.05%. CD spectra of these analogues were indistinguishable from each other and
      identical to that of bombyxin. Changing the backbone structure by replacing
      alanine with glycine and alpha-aminoisobutyric acid resulted in analogues with
      activities of 3.7 and 1.4%, respectively, but also a disturbed structure as
      determined by CD spectroscopy. Replacement of other residues on the periphery of
      the trough, i.e., arginines at positions B12 and B16, also reduced the level of
      receptor binding but to a lesser extent than the replacement of alanine(B15). The
      level of receptor binding for citrulline(B12) bombyxin was 17% and for
      citrulline(B16) bombyxin was 45%. When it is considered that glycine(A1) is
      located on the edge of the same trough but across from Ala(B15) and is required
      for maintenance of the overall structure of bombyxin, it is proposed that the
      bombyxin receptor binding site forms a contiguous hydrophobic area consisting of
      residues Ile(A2), Leu(B14), and Ala(B15).

PMID- 10933789
TI  - Structural studies of the high mobility group globular domain and basic tail of
      HMG-D bound to disulfide cross-linked DNA.
AB  - HMG-D is an abundant high mobility group chromosomal protein present during early
      embryogenesis in Drosophila melanogaster. It is a non-sequence-specific member of
      a protein family that uses the HMG domain for binding to DNA in the minor groove.
      The highly charged C-terminal tail of HMG-D contains AK motifs that contribute to
      high-affinity non-sequence-specific DNA binding. To understand the interactions
      of the HMG domain and C-terminal tail of HMG-D with DNA in solution, a complex
      between a high-affinity truncated form of the protein and a disulfide cross
      linked DNA fragment was studied using heteronuclear NMR techniques. Despite its
      relatively high affinity for the single "prebent" site on the DNA, K(d) = 1.4 nM,
      HMG-D forms a non-sequence-specific complex with the DNA as indicated by exchange
      broadening of the protein resonances at the DNA interface in solution. The
      secondary structural elements of the protein are preserved when the protein is
      complexed with the DNA, and the DNA-binding interface maps to the regions of the
      protein where the largest chemical shift differences occur. The C-terminal tail
      of HMG-D confers high-affinity DNA binding, has an undefined structure, and
      appears to make direct contacts in the major groove of DNA via residues that are
      potentially regulated by phosphorylation. We conclude that while the HMG domain
      of HMG-D recognizes DNA with a mode of binding similar to that used by the
      sequence-specific HMG domain transcription factors, there are noteworthy
      differences in the structure and interactions of the C-terminal end of the DNA
      binding domain and the C-terminal tail.

PMID- 10933790
TI  - Specificity of lipid incorporation is determined by sequences in the N-terminal
      37 of apoB.
AB  - The N-terminal 17% of apolipoprotein B (apoB-17) is secreted lipid-poor while
      apoB-41 particles are secreted with a triacylglycerol (TAG)-rich core. Thus, the
      sequence between apoB-17 and apoB-41 is necessary for the assembly of TAG-rich
      lipoproteins. To delineate this region, C127 cells were permanently transfected
      to secrete the N-terminal 29, 32.5, or 37% of apoB. Density gradient
      centrifugation showed that secreted apoB-29, apoB-32.5, and apoB-37 had peak
      densities of 1.25, 1.22, and 1.16 g/mL and percent lipid of particle weights of
      30, 37, and 49%, respectively. Calculated anhydrous particle diameters were: apoB
      29 = 81 A, apoB-32.5 = 88 A, and apoB-37 = 101 A. Immunoprecipitated particles
      labeled with [(3)H]oleate showed that, as apoB length increased from apoB-29 to
      apoB-32.5 and apoB-37, the number of TAG (core) molecules per apoB particle
      increased almost 16-fold from 8 to 32 to 124, while phospholipids and
      diacylglycerols (surface lipids) increased only slightly from 71 to 87 to 97
      molecules, respectively. Thus, sequences in the C-terminus of apoB-29 bind
      phospholipids and diacylglycerols, sequences between apoB-29 and apoB-32.5
      augment TAG binding and sequences between apoB-32.5 and apoB-41 account for the
      marked incorporation of TAG at a rate of approximately 1 TAG per 2 amino acids.
      Cryoelectron micrographs of isolated apoB-37 particles revealed mostly spherical
      particles of approximately 110 A (11.0 nm) with an electron lucent center,
      consistent with these particles having a TAG core. We suggest that the predicted
      amphipathic beta-sheets beginning at apoB-29, starts to preferentially recruit
      core lipids into apoB and propose that the consistent presence of DAG in the
      secreted particles may have a role in fission of the nascent lipoprotein
      particles from the endoplasmic reticulum membrane.

PMID- 10933791
TI  - Temperature effects on the catalytic efficiency, rate enhancement, and transition
      state affinity of cytidine deaminase, and the thermodynamic consequences for
      catalysis of removing a substrate "anchor".
AB  - To obtain a clearer understanding of the forces involved in transition state
      stabilization by Escherichia coli cytidine deaminase, we investigated the
      thermodynamic changes that accompany substrate binding in the ground state and
      transition state for substrate hydrolysis. Viscosity studies indicate that the
      action of cytidine deaminase is not diffusion-limited. Thus, K(m) appears to be a
      true dissociation constant, and k(cat) describes the chemical reaction of the ES
      complex, not product release. Enzyme-substrate association is accompanied by a
      loss of entropy and a somewhat greater release of enthalpy. As the ES complex
      proceeds to the transition state (ES), there is little further change in entropy,
      but heat is taken up that almost matches the heat that was released with ES
      formation. As a result, k(cat)/K(m) (describing the overall conversion of the
      free substrate to ES is almost invariant with changing temperature. The free
      energy barrier for the enzyme-catalyzed reaction (k(cat)/K(m)) is much lower than
      that for the spontaneous reaction (k(non)) (DeltaDeltaG = -21.8 kcal/mol at 25
      degrees C). This difference, which also describes the virtual binding affinity of
      the enzyme for the activated substrate in the transition state (S), is almost
      entirely enthalpic in origin (DeltaDeltaH = -20.2 kcal/mol), compatible with the
      formation of hydrogen bonds that stabilize the ES complex. Thus, the transition
      state affinity of cytidine deaminase increases rapidly with decreasing
      temperature. When a hydrogen bond between Glu-91 and the 3'-hydroxyl moiety of
      cytidine is disrupted by truncation of either group, k(cat)/K(m) and transition
      state affinity are each reduced by a factor of 10(4). This effect of mutation is
      entirely enthalpic in origin (DeltaDeltaH approximately 7.9 kcal/mol), somewhat
      offset by a favorable change in the entropy of transition state binding. This
      increase in entropy is attributed to a loss of constraints on the relative
      motions of the activated substrate within the ES complex. In an Appendix, some
      objections to the conventional scheme for transition state binding are discussed.

PMID- 10933792
TI  - Mechanism of the bisphosphatase reaction of 6-phosphofructo-2-kinase/fructose-2,6
      bisphosphatase probed by (1)H-(15)N NMR spectroscopy.
AB  - The histidines in the bisphosphatase domain of rat liver 6-phosphofructo-2
      kinase/fructose-2,6-bisphosphatase were labeled with (15)N, both specifically at
      N1' and globally, for use in heteronuclear single quantum correlation (HSQC) NMR
      spectroscopic analyses. The histidine-associated (15)N resonances were assigned
      by correlation to the C2' protons which had been assigned previously [Okar et
      al., Biochemistry 38, 1999, 4471-79]. Acquisition of the (1)H-(15)N HSQC from a
      phosphate-free sample demonstrated that the existence of His-258 in the rare N1'
      tautomeric state is dependent upon occupation of the phosphate binding site
      filled by the O2 phosphate of the substrate, fructose-2,6-bisphosphate, and
      subsequently, the phosphohistidine intermediate. The phosphohistidine
      intermediate is characterized by two hydrogen bonds involving the catalytic
      histidines, His-258 and His-392, which are directly observed at the N1' positions
      of the imidazole rings. The N1' of phospho-His-258 is protonated ((1)H chemical
      shift, 14.0 ppm) and hydrogen bonded to the backbone carbonyl of Gly-259. The N1'
      of cationic His-392 is hydrogen bonded ((1)H chemical shift, 13.5 ppm) to the
      phosphoryl moiety of the phosphohistidine. The existence of a protonated phospho
      His-258 intermediate and the observation of a fairly strong hydrogen bond to the
      same phosphohistidine implies that hydrolysis of the covalent intermediate
      proceeds without any requirement for an "activated" water. Using the labeled
      histidines as probes of the catalytic site mutation of Glu-327 to alanine
      revealed that, in addition to its function as the proton donor to fructose-6
      phosphate during formation of the transient phosphohistidine intermediate at the
      N3' of His-258, this residue has a significant role in maintaining the structural
      integrity of the catalytic site. The (1)H-(15)N HSQC data also provide clear
      evidence that despite being a surface residue, His-446 has a very acidic pK(a),
      much less than 6.0. On the basis of these observations a revised mechanism for
      fructose-2,6-bisphosphatase that is consistent with all of the previously
      published kinetic data and X-ray crystal structures is proposed. The revised
      mechanism accounts for the structural and kinetic consequences produced by
      mutation of the catalytic histidines and Glu-327. It also provides the basis for
      a hypothetical mechanism of bisphosphatase activation by cAMP-dependent
      phosphorylation of Ser-32, which is located in the N-terminal kinase domain.

PMID- 10933793
TI  - Investigation of human low-density lipoprotein by (1)H nuclear magnetic resonance
      spectroscopy: mobility of phosphatidylcholine and sphingomyelin headgroups
      characterizes the surface layer.
AB  - The resolution of the trimethyl headgroup resonance of phosphatidylcholine (PC)
      and sphingomyelin (SM) in the intact human low-density lipoprotein (LDL) (1)H NMR
      spectrum at 600 MHz enabled the investigation of LDL surface structure and
      phospholipid-apoB interactions. We have previously shown that a higher proportion
      of PC headgroups (25-35% of total PC in LDL) compared to SM were tightly bound to
      apoB and therefore NMR-invisible [Murphy, H. C., et al. (1997) Biochem. Biophys.
      Res. Commun. 234 (3), 733-737]. In the present study, we have investigated the
      mobility of phospholipid (PL) headgroups, using (1)H NMR spin-spin (T(2))
      relaxation measurements, in LDL isolated from nine volunteers. We show that both
      PC and SM exist in two additional and distinct environments indicated by the
      biexponential behavior of the relaxation decays in each case. The data showed
      that 36% of PC headgroups had a short T(2) component, mean T(2) of 31 ms, and 64%
      had a longer T(2) component of 54 ms. Approximately 15% of SM headgroups had a
      short T(2) component (mean T(2) of 27 ms) and 85% had a longer T(2) component of
      78 ms. Therefore the majority of SM headgroups (85%) were more mobile than PC (P
      < 0.001) and since PC headgroups in organic media were more mobile than SM, we
      conclude that the characteristic high mobility of LDL SM is not an intrinsic
      property but arises from a high degree of order in molecular packing of the
      surface PL of human LDL. We suggest that because PC and SM interact
      differentially with cholesterol and possibly with neighboring phospholipids, this
      results in the formation of relatively long-lived microdomains of PL in vivo.

PMID- 10933794
TI  - Inhibition of expression of the type I G protein-coupled receptor for vasoactive
      intestinal peptide (VPAC1) by hammerhead ribozymes.
AB  - Vasoactive intestinal peptide (VIP) is a neuromediator expressed widely in the
      nervous, gastrointestinal, respiratory, and immune systems. Two G protein-coupled
      receptors (GPCRs), designated VPAC1 and VPAC2, bind VIP with high affinity and
      transduce increases in [cyclic AMP](i) and [Ca(2+)](i). As there are no potent
      VPAC1- or VPAC2-selective antagonists, a hammerhead ribozyme (Rz) strategy
      capable of in vivo application was adopted to inactivate individual domains of
      VPAC1. Three Rzs were designed to cleave mRNA encoding the amino terminus, the
      third intracellular loop, and the cytoplasmic tail of human VPAC1 and were
      introduced by transfection into HEK-293 cells expressing recombinant human VPAC1.
      Each Rz specifically degraded VPAC1 mRNA and down-regulated VPAC1 protein and VIP
      binding activity, as assessed by ribonuclease protection assays, Western blots,
      and binding of (125)I-VIP. Rz-mediated down-regulation of VPAC1 was associated
      with up to 75% suppression of VIP signaling of increases in [cyclic AMP](i) and
      [IP3](i), and of cyclic AMP response element-luciferase reports. The Rz specific
      for the amino terminus inhibited VPAC1 expression and signaling to the greatest
      extent. VIP-evoked cellular responses thus appear to be proportional to the level
      of VPAC1 expression. Specific Rzs may be powerful tools for manipulating tissue
      specific contributions of GPCRs in vitro and in vivo.

PMID- 10933795
TI  - Packing of the transmembrane helices of Na,K-ATPase: direct contact between beta
      subunit and H8 segment of alpha-subunit revealed by oxidative cross-linking.
AB  - Spatial relationships among the transmembrane (TM) segments of alpha- and beta
      subunits of the Na,K-ATPase molecule have been investigated using oxidative
      induction of disulfide bonds. The catalytic alpha-subunit contains 10 TM alpha
      helices (H1-H10) with 9 Cys residues located within or close to the membrane
      moiety. There is one Cys residue in the single TM segment of beta-subunit
      (Hbeta). Previously, the cross-linking products containing the beta-subunit and
      two fragments of alpha-subunit (the N-terminal containing H1-H2 helices and the C
      terminal containing H7-H10 helices) have been identified in experiments with
      membrane-bound or detergent-solubilized preparations of the membrane moiety of
      trypsin-digested Na,K-ATPase [Sarvazyan, N. A., Modyanov, N. N., and Askari, A.
      (1995) J. Biol. Chem. 270, 26528-26532 and Sarvazyan, N. A., Ivanov, A.,
      Modyanov, N. N., and Askari, A. (1997) J. Biol. Chem. 272, 7855-7858]. Here, we
      have shown that Cu(2+)-phenanthroline treatment of digitonin-solubilized
      preparation provides the most efficient formation of intersubunit cross-linked
      product that is predominantly a dimer of beta-subunit and a 22-kDa C-terminal
      alpha-fragment containing H7-H10 helices. This cross-linked product was isolated
      and subjected to CNBr cleavage. The resulting fragments were electrophoretically
      separated and sequenced. A 17-kDa peptide composed of Ile853-Met942 alpha
      fragment and Ala5-Met56 beta-fragment was identified as a product of intersubunit
      disulfide cross-link between Cys44 of Hbeta and either Cys911 or Cys930, located
      in H8. This provides the first direct experimental evidence of the juxtaposition
      of Hbeta and H8 within the Na,K-ATPase molecule. The second detected cross-linked
      product was composed of alpha-fragments Lys947-Met963 and Tyr974-Tyr1016 linked
      by induced disulfide bridge between Cys964 (H9) and Cys983 (H10). The spatial
      proximity of these Cys residues defines the mutual orientation of H9 and H10
      helices of alpha-subunit.

PMID- 10933796
TI  - Insights into the HER-2 receptor tyrosine kinase mechanism and substrate
      specificity using a transient kinetic analysis.
AB  - The HER-2/erbB-2/c-neu proto-oncogene encodes for an EGF receptor-like protein
      which has been implicated in the pathogenesis of several human malignancies.
      Although much has been learned about the physiological significance of this
      receptor tyrosine kinase, its catalytic mechanism remains poorly understood. We
      have expressed, purified, and characterized two recombinant proteins
      corresponding to a full-length (HCD) and truncated (HKD) construct of the HER-2
      intracellular tyrosine kinase domain and have identified an optimal substrate
      (GGMEDIYFEFMGGKKK; HER2Peptide) through screening of a degenerate peptide
      library. We have conducted a transient kinetic analysis of the HER-2 proteins
      (HCD and HKD) to illuminate mechanistic details of the HER-2 pathway. In
      particular, stopped-flow fluorescence studies with mant (N-methylanthraniloyl)
      nucleotide derivatives provided direct measurements of the association and
      dissociation rate constants for these nucleotide interactions with the HER-2
      recombinant proteins, thereby enabling the determination of nucleotide K(d)
      values. Moreover, the actual step of chemical catalysis was isolated using rapid
      chemical quench techniques and shown to occur approximately 3-fold faster than
      the steady-state rate which corresponds to product release. Evidence is also
      provided that suggests a conformational change that is partially rate-limiting at
      least in HCD. Furthermore, the role that the phosphorylation state of the protein
      may play on catalysis was examined. Studies carried out with pre-phosphorylated
      recombinant HER-2 proteins suggest that while autophosphorylation is not a
      prerequisite for enzymatic activity, this protein modification actually directly
      affects the catalytic mechanism by enhancing the rate of ADP release and that of
      the rate-limiting step. While a pre-steady-state kinetic analysis has been
      carried out on the catalytic subunit of cAMP-dependent serine/threonine kinase,
      to our knowledge, this study represents the first reported transient kinetic
      investigation of a receptor tyrosine kinase. This work serves as a basis for
      comparison of these two important protein kinase families and in this report we
      highlight these similarities and differences.

PMID- 10933797
TI  - Asp338 controls hydride transfer in Escherichia coli IMP dehydrogenase.
AB  - IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with the
      concomitant reduction of NAD(+). This reaction involves the formation of a
      covalent adduct with an active site Cys. This intermediate, E-XMP, hydrolyzes to
      produce XMP. The mutation of Asp338 to Ala severely impairs the activity of
      Escherichia coli IMPDH, decreasing the value of k(cat) by 650-fold. No (D)V(m) or
      (D)V/K(m) isotope effects are observed when 2-(2)H-IMP is the substrate for wild
      type IMPDH. Values of (D)V(m) = 2.6 and (D)V/K(m) (IMP) = 3.4 are observed for
      Asp338Ala. Moreover, while a burst of NADH production is observed for wild-type
      IMPDH, no burst is observed for Asp338Ala. These observations indicate that the
      mutation has decreased the rate of hydride transfer by at least 5 x 10(3)-fold.
      In contrast, k(cat) for the hydrolysis of 2-chloroinosine-5'-monophosphate is
      decreased by only 8-fold. In addition, the rate constant for inactivation by 6
      chloropurine riboside 5'-monophosphate is increased by 3-fold. These observations
      suggest that the mutation has little effect on the nucleophilicity of the active
      site Cys residue. These results are consistent with a recent crystal structure
      that shows a hydrogen bonding network between Asp338, the 2'-OH of IMP, and the
      amide group of NAD(+) [Colby, T. D., Vanderveen, K., Strickler, M. D., Markham,
      G. D., and Goldstein, B. M. (1999) Proc. Natl. Acad. Sci. U.S.A. 96, 3531-3536].

PMID- 10933798
TI  - Substrate binding stabilizes S-adenosylhomocysteine hydrolase in a closed
      conformation.
AB  - Comparison of crystal structures of S-adenosylhomocysteine (AdoHcy) hydrolase in
      the substrate-free, NAD(+) form [Hu, Y., Komoto, J., Huang, Y., Gomi, T., Ogawa,
      H., Takata, Y., Fujioka, M., and Takusagawa, F. (1999) Biochemistry 38, 8323
      8333] and a substrate-bound, NADH form [Turner, M. A., Yuan, C.-S., Borchardt, R.
      T., Hershfield, M. S., Smith, G. D., and Howell, P. L. (1998) Nat. Struct. Biol.
      5, 369-376] indicates large differences in the spatial arrangement of the
      catalytic and NAD(+) binding domains. The substrate-free, NAD(+) form exists in
      an "open" form with respect to catalytic and NAD(+) binding domains, whereas the
      substrate-bound, NADH form exists in a closed form with respect to those domains.
      To address whether domain closure is induced by substrate binding or its
      subsequent oxidation, we have measured the rotational dynamics of spectroscopic
      probes covalently bound to Cys(113) and Cys(421) within the catalytic and
      carboxyl-terminal domains. An independent domain motion is associated with the
      catalytic domain prior to substrate binding, suggesting the presence of a
      flexible hinge element between the catalytic and NAD(+) binding domains.
      Following binding of substrates (i.e., adenosine or neplanocin A) or a
      nonsubstrate (i.e., 3'-deoxyadenosine), the independent domain motion associated
      with the catalytic domain is essentially abolished. Likewise, there is a
      substantial decrease in the average hydrodynamic volume of the protein that is
      consistent with a reduction in the overall dimensions of the homotetrameric
      enzyme following substrate binding and oxidation observed in earlier
      crystallographic studies. Thus, the catalytic and NAD(+) binding domains are
      stabilized to form a closed active site through interactions with the substrate
      prior to substrate oxidation.

PMID- 10933799
TI  - NMR studies of ligand carboxylate group interactions with arginine residues in
      complexes of Lactobacillus casei dihydrofolate reductase with substrates and
      substrate analogues.
AB  - In a series of complexes of Lactobacillus casei dihydrofolate reductase (DHFR)
      formed with substrates and substrate analogues, the (1)H/(15)N NMR chemical
      shifts for the guanidino group of the conserved Arg 57 residue were found to be
      sensitive to the mode of binding of their H(eta) protons to the charged oxygen
      atoms in ligand carboxylate groups. In all cases, Arg 57 showed four
      nonequivalent H(eta) signals indicating hindered rotation about the N(epsilon)
      C(zeta) and C(zeta)-N(eta) bonds. The H(eta)(12) and H(eta)(22) protons have
      large downfield shifts as expected for a symmetrical end-on interaction with the
      ligand carboxylate group. The chemical shifts are essentially the same in the
      complexes with folate and p-aminobenzoyl-L-glutamate (PABG) and similar to those
      found previously for the methotrexate complex reflecting the strong and similar
      hydrogen bonds formed with the carboxylate oxygens. Interestingly, the rates of
      rotation about the N(epsilon)-C(zeta) bond for the complexes containing the
      weakly binding PABG fragment are almost identical to those measured in the
      complex with methotrexate, which binds 10(7) times more tightly. In the
      methotrexate complex, this rotation depends on correlated rotations about the
      N(epsilon)-C(zeta) bond of Arg 57 and the C(alpha)-C' bond of the ligand
      glutamate alpha-carboxylate group. Thus, even in a fragment such as PABG, which
      has a much faster off-rate, the carboxylate group binds to the enzyme in a
      similar way to that in a parent molecule such as folate and methotrexate with the
      rotation about the N(epsilon)-C(zeta) bond of Arg 57 being essentially the same
      in all the different complexes.

PMID- 10933800
TI  - Identification of Asp-130 as the catalytic nucleophile in the main alpha
      galactosidase from Phanerochaete chrysosporium, a family 27 glycosyl hydrolase.
AB  - Characterization of the complete gene sequence encoding the alpha-galactosidase
      from Phanerochaete chrysosporium confirms that this enzyme is a member of
      glycosyl hydrolase family 27 [Henrissat, B., and Bairoch, A. (1996) Biochem. J.
      316, 695-696]. This family, together with the family 36 alpha-galactosidases,
      forms glycosyl hydrolase clan GH-D, a superfamily of alpha-galactosidases, alpha
      N-acetylgalactosaminidases, and isomaltodextranases which are likely to share a
      common catalytic mechanism and structural topology. Identification of the active
      site catalytic nucleophile was achieved by labeling with the mechanism-based
      inactivator 2',4', 6'-trinitrophenyl 2-deoxy-2,2-difluoro-alpha-D-lyxo
      hexopyranoside; this inactivator was synthesized by anomeric deprotection of the
      known 1,3,4,6-tetra-O-acetyl-2-deoxy-2, 2-difluoro-D-lyxo-hexopyranoside
      [McCarter, J. D., Adam, M. J., Braun, C., Namchuk, M., Tull, D., and Withers, S.
      G. (1993) Carbohydr. Res. 249, 77-90], picrylation with picryl fluoride and 2, 6
      di-tert-butylpyridine, and O-deacetylation with methanolic HCl. Enzyme
      inactivation is a result of the formation of a stable 2-deoxy-2,2-difluoro-beta-D
      lyxo-hexopyranosyl-enzyme intermediate. Following peptic digestion, comparative
      liquid chromatographic/mass spectrometric analysis of inactivated and control
      enzyme samples served to identify the covalently modified peptide. After
      purification of the labeled peptide, benzylamine was shown to successfully
      replace the 2-deoxy-2,2-difluoro-D-lyxo-hexopyranosyl peptidyl ester by
      aminolysis. The labeled amino acid was identified as Asp-130 of the mature
      protein by further tandem mass spectrometric analysis of the native and
      derivatized peptides in combination with Edman degradation analysis. Asp-130 is
      found within the sequence YLKYDNC, which is highly conserved in all known family
      27 glycosyl hydrolases.

PMID- 10933801
TI  - Phosphorylation of human p53 on Thr-55.
AB  - The pleiotropic function of p53 is believed to be greatly influenced by
      phosphorylation, and several sites on p53 are known to be targets for distinct
      protein kinases. In this study, we observed that affinity-purified p53 from
      overexpressing cells was phosphorylated by a co-purified protein kinase in vitro.
      To identify phosphorylation site(s), the resulting phosphorylated p53 protein was
      subjected to primary and secondary proteolytic cleavage, and phosphopeptides were
      fractionated by a two-dimensional peptide gel system. Phosphoamino acid analysis
      and manual Edman degradation of the isolated phosphopeptides enabled us to
      unequivocally identify Thr-55 as the major phosphorylation site on p53.
      Furthermore, comparative phosphopeptide mapping data suggest that DNA-PK is not
      the kinase responsible for this phosphorylation. Significantly, using a phospho
      specific antibody for Thr-55, we have shown that Thr-55 is indeed phosphorylated
      in vivo. These data define Thr-55 as a novel phosphorylation site and for the
      first time show threonine phosphorylation of human p53.

PMID- 10933802
TI  - Decreased lateral aggregation of a variant recombinant fibrinogen provides
      insight into the polymerization mechanism.
AB  - We analyzed the polymerization of BbetaA68T fibrinogen, the recombinant
      counterpart of fibrinogen Naples, a variant known to have decreased thrombin
      binding. When polymerized with equal thrombin concentrations, BbetaA68T
      fibrinogen had a longer lag time and lower rate of lateral aggregation, V(max),
      than normal recombinant fibrinogen, but a similar final turbidity. At thrombin
      concentrations that equalized the rates of fibrinopeptide A release, BbetaA68T
      fibrinogen polymerized with a lag time and V(max) similar to normal, but reached
      a significantly lower final turbidity. Similar results were produced when
      BbetaA68T was polymerized with Ancrod, which cleaves fibrinopeptide A at the same
      rate from either fibrinogen, and when BbetaA68T desA monomers were polymerized.
      The polymerization of desAB fibrin monomers, which circumvents fibrinopeptide
      release, was the same for both fibrinogens. We confirmed that turbidity was
      indicative of fiber thickness by scanning electron microscopy of fibrin clots.
      Here, we present the first experimental evidence of fibrin polymerization with a
      normal period of protofibril formation and rate of lateral aggregation, but with
      a significantly decreased extent of lateral aggregation. We conclude that the
      decreased lateral aggregation seen in BbetaA68T fibrinogen is due to an altered
      step in the enzymatic phase of its polymerization process. We propose that during
      normal polymerization a subtle conformational change in the E domain occurs,
      between the release of FpA and FpB, and that this change modulates the mechanism
      of lateral aggregation. Without this change, the lateral aggregation of BbetaA68T
      fibrinogen is impaired such that variant clots have thinner fibers than normal
      clots.

PMID- 10933803
TI  - Zymogen factor IX potentiates factor IXa-catalyzed factor X activation.
AB  - Intrinsic factor X activation is accelerated >10(7)-fold by assembly of the
      entire complex on the activated platelet surface. We have now observed that
      increasing the concentration of zymogen factor IX to physiologic levels (
      approximately 100 nM) potentiates factor IXa-catalyzed activation of factor X on
      both activated platelets and on negatively charged phospholipid vesicles. In the
      presence and absence of factor VIIIa, factor IX (100 nM) lowered the K(d,appFIXa)
      approximately 4-fold on platelets and 2-10-fold on lipid vesicles. Treatment of
      two factor IX preparations with active-site inhibitors did not affect these
      observations. Autoradiographs of PAGE-separated reactions containing either
      (125)I-labeled factor IX or (125)I-labeled factor X showed that the increased
      factor X activation was not due to factor Xa-mediated feedback activation of
      factor IX and that there was increased cleavage of factor X heavy chain in the
      presence of factor IX in comparison with control reactions but only in the
      presence of both the enzyme and the surface. Since plasma concentrations of
      prothrombin, factor VII, protein C, or protein S did not by themselves potentiate
      factor Xa generation and did not interfere with the potentiation of the reaction
      of factor IX, the effect is specific for factor IX and is not attributable to the
      Gla domain of all vitamin K-dependent proteins. These observations indicate that
      under physiologic conditions, plasma levels of the zymogen factor IX specifically
      increase the affinity of factor IXa for the intrinsic factor X activation
      complex.

PMID- 10933804
TI  - Isolation and characterization of EMS16, a C-lectin type protein from Echis
      multisquamatus venom, a potent and selective inhibitor of the alpha2beta1
      integrin.
AB  - We have isolated and characterized EMS16, a potent and selective inhibitor of the
      alpha2beta1 integrin, from Echis multisquamatus venom. It belongs to the family
      of C-lectin type of proteins (CLPs), and its amino acid sequence is homologous
      with other members of this protein family occurring in snake venoms. EMS16 (M(r)
      approximately 33K) is a heterodimer composed of two distinct subunits linked by S
      S bonds. K562 cells transfected with alpha2 integrin selectively adhere to
      immobilized EMS16, but not to two other snake venom-derived CLPs, echicetin and
      alboaggregin B. EMS16 inhibits adhesion of alpha2beta1-expressing cells to
      immobilized collagen I at picomolar concentrations, and the platelet/collagen I
      interaction in solution at nanomolar concentrations. EMS16 inhibits binding of
      isolated, recombinant I domain of alpha2 integrin to collagen in an ELISA assay,
      but not the interaction of isolated I domain of alpha1 integrin with collagen IV.
      Studies with monoclonal antibodies suggested that EMS16 binds to the alpha2
      subunit of the integrin. EMS16 inhibits collagen-induced platelet aggregation,
      but has no effect on aggregation induced by other agonists such as ADP,
      thromboxane analogue (U46619), TRAP, or convulxin. EMS16 also inhibits collagen
      induced, but not convulxin-induced, platelet cytosolic Ca(2+) mobilization. In
      addition, EMS16 inhibits HUVEC migration in collagen I gel. In conclusion, we
      report a new, potent viper venom-derived inhibitor of alpha2beta1 integrin, which
      does not belong to the disintegrin family.

PMID- 10933806
TI  - Mixed membranes of sphingolipids and glycerolipids as studied by spin-label ESR
      spectroscopy. A search for domain formation.
AB  - The temperature dependences of the ESR spectra from different positional isomers
      of sphingomyelin and of phosphatidylcholine spin-labeled in their acyl chain have
      been compared in mixed membranes composed of sphingolipids and glycerolipids. The
      purpose of the study was to identify the possible formation of sphingolipid-rich
      in-plane membrane domains. The principal mixtures that were studied contained
      sphingomyelin and the corresponding glycerolipid phosphatidylcholine, both from
      egg yolk. Other sphingolipids that were investigated were brain cerebrosides and
      brain gangliosides, in addition to sphingomyelins from brain and milk. The outer
      hyperfine splittings in the ESR spectra of sphingomyelin and of
      phosphatidylcholine spin-labeled on C-5 of the acyl chain were consistent with
      mixing of the sphingolipid and glycerolipid components, in fluid-phase membranes.
      In the gel phase of egg sphingomyelin and its mixtures with phosphatidylcholine,
      the outer hyperfine splittings of sphingomyelin spin-labeled at C-14 of the acyl
      chain of sphingomyelin are smaller than those of the corresponding sn-2 chain
      spin-labeled phosphatidylcholine. This is in contrast to the situation with
      sphingomyelin and phosphatidylcholine spin-labeled at C-5, for which the outer
      hyperfine splitting is always greater for the spin-labeled sphingomyelin. The
      behavior of the C-14 spin-labels is attributed to a different geometry of the
      acyl chain attachments of the sphingolipids and glycerolipids that is consistent
      with their respective crystal structures. The two-component ESR spectra of
      sphingomyelin and phosphatidylcholine spin-labeled at C-14 of the acyl chain
      directly demonstrate a broad two-phase region with coexisting gel and fluid
      domains in sphingolipid mixtures with phosphatidylcholine. Domain formation in
      membranes composed of sphingolipids and glycerolipids alone is related primarily
      to the higher chain-melting transition temperature of the sphingolipid component.

PMID- 10933805
TI  - R-domain interactions with distal regions of CFTR lead to phosphorylation and
      activation.
AB  - Cystic fibrosis is caused by the aberrant function of the cystic fibrosis
      transmembrane conductance regulator (CFTR) protein. We examined whether
      intramolecular binding interactions involving the regulatory (R) domain
      contributed to CFTR regulation and function. When the R-domain (amino acids 596
      836) was coexpressed with Delta1-836 CFTR (a carboxyl hemi-CFTR beginning
      immediately after the R-domain), strong binding between the two polypeptides was
      exhibited. The R-domain that co-immunoprecipitated with Delta1-836 exhibited a
      slower mobility on SDS-PAGE that resulted from phosphorylation of the protein. A
      larger CFTR polypeptide that included the R-domain (M837X) also exhibited a
      phosphorylation-dependent mobility shift when coexpressed with Delta1-836.
      Moreover, coexpression of M837X and Delta1-836 led to enhanced halide
      permeability in living cells. The activity, unlike in full-length CFTR, was
      present without forskolin activation, but still sensitive to the PKA inhibitor,
      Rp-8-CPT-cAMPS. This PKA inhibition of activity was found to be dependent on the
      carboxy region of the R-domain, amino acids 723-836. Our results indicate that
      the R-domain binds CFTR residues after amino acid 836 and that this binding
      facilitates phosphorylation and CFTR activation. We have also characterized a
      subdomain within CFTR (residues 723-837) that is necessary for PKA-dependent
      constitutive activation. Finally, these experiments demonstrate that constitutive
      CFTR activity can be accomplished by at least two mechanisms: (1) direct
      modulation of the R-domain to abrogate PKA regulation and (2) modifications that
      increase R-domain susceptibility to steady-state phosphorylation through PKA.

PMID- 10933807
TI  - Simultaneous phosphorylation of Ser11 and Ser18 in the alpha-subunit promotes the
      recruitment of Na(+),K(+)-ATPase molecules to the plasma membrane.
AB  - Renal sodium homeostasis is a major determinant of blood pressure and is
      regulated by several natriuretic and antinatriuretic hormones. These hormones,
      acting through intracellular second messengers, either activate or inhibit
      proximal tubule Na(+),K(+)-ATPase. We have shown previously that phorbol ester
      (PMA) stimulation of endogenous PKC leads to activation of Na(+),K(+)-ATPase in
      cultured proximal tubule cells (OK cells) expressing the rodent Na(+), K(+)
      ATPase alpha-subunit. We have now demonstrated that the treatment with PMA leads
      to an increased amount of Na(+),K(+)-ATPase molecules in the plasmalemma, which
      is proportional to the increased enzyme activity. Colchicine, dinitrophenol, and
      potassium cyanide prevented the PMA-dependent stimulation of activity without
      affecting the increased level of phosphorylation of the Na(+), K(+)-ATPase alpha
      subunit. This suggests that phosphorylation does not directly stimulate
      Na(+),K(+)-ATPase activity; instead, phosphorylation may be the triggering
      mechanism for recruitment of Na(+),K(+)-ATPase molecules to the plasma membrane.
      Transfected cells expressing either an S11A or S18A mutant had the same basal
      Na(+),K(+)-ATPase activity as cells expressing the wild-type rodent alpha
      subunit, but PMA stimulation of Na(+),K(+)-ATPase activity was completely
      abolished in either mutant. PMA treatment led to phosphorylation of the alpha
      subunit by stimulation of PKC-beta, and the extent of this phosphorylation was
      greatly reduced in the S11A and S18A mutants. These results indicate that both
      Ser11 and Ser18 of the alpha-subunit are essential for PMA stimulation of Na(+),
      K(+)-ATPase activity, and that these amino acids are phosphorylated during this
      process. The results presented here support the hypothesis that PMA regulation of
      Na(+),K(+)-ATPase is the result of an increased number of Na(+),K(+)-ATPase
      molecules in the plasma membrane.

PMID- 10933808
TI  - SH3 binding sites of ZG29p mediate an interaction with amylase and are involved
      in condensation-sorting in the exocrine rat pancreas.
AB  - ZG29p, a novel pancreas-specific zymogen granule protein, has been proposed to
      act as a 'helper protein' in granule formation. To address its function in more
      detail, we searched for putative binding partners of ZG29p. In zymogen complexes
      isolated by nondenaturing isoelectric focusing, ZG29p was associated with a
      protein complex consisting of amylase and cationic trysinogen. Amylase also
      coeluted with ZG29p after immunoaffinity chromatography using an antibody to
      recombinant ZG29p. Cross-linking experiments with granule content proteins
      revealed a direct interaction between recombinant ZG29p and amylase. An
      interaction was also observed when purified amylase was used, whereas no
      interaction with recombinant or purified cationic trypsinogen was seen. ZG29p
      could also be cross-linked to three membrane proteins with molecular masses of
      40, 18, and 16 kDa. The binding of ZG29p to amylase and to the membrane proteins
      was inhibited in the presence of synthetic peptides matching the consensus
      sequence of proline-rich SH3 binding sites present in ZG29p. The synthetic
      peptides could be cross-linked to amylase and to three yet unidentified acidic
      content proteins with molecular masses of about 30 kDa. The peptides also
      interacted with purified or recombinant amylase, but not with recombinant or
      purified cationic trypsinogen. In a condensation-sorting assay, the binding
      (sorting) of zymogen complexes to the granule membrane was reduced in the
      presence of the peptides. Our results indicate that the interaction of ZG29p with
      amylase is mediated by SH3 binding domains and that these domains are involved in
      the sorting of amylase to the granule membrane.

PMID- 10933809
TI  - Recruitment and activation of Raf-1 kinase by nitric oxide-activated Ras.
AB  - Nitric oxide (NO) and related species serve as cellular messengers in various
      physiological and pathological processes. The monomeric G protein, Ras,
      transduces multiple signaling pathways with varying biological responses. We have
      previously reported that NO triggers Ras activation and recruitment of an
      effector, phosphatidylinositol 3'-kinase (PI3K) and Ras-dependent activation of
      mitogen-activated protein (MAP) kinases which include extracellular signal
      regulated kinases (ERKs), c-Jun NH(2)-terminal kinase (JNK), and p38 MAP kinase.
      In this study, we further defined NO-activated Ras signaling pathways. We have
      identified Raf-1 as another effector recruited by NO-activated Ras in T
      lymphocytes. NO activation results in association of Ras and Raf-1 and is
      biologically significant, as we observe an NO-induced increase in Raf-1 kinase
      activity. Downstream to Raf-1 kinase lie MAP kinases and their subsequent
      downstream targets, transcription factors. We found that treatment of T
      lymphocytes with NO yielded phosphorylation of the transcription factor, Elk-1.
      This phoshorylation is dependent on NO binding to the cysteine 118 residue of
      Ras. By further delineating the pathway with pharmacological inhibitors, Elk-1
      phosphorylation was also found to be dependent on PI3K and ERK. Moreover, NO
      triggered an increase in mRNA levels of the proinflammatory cytokine, tumor
      necrosis factor-alpha (TNF-alpha), which was ERK dependent. Thus, we have defined
      an NO-induced signaling pathway in T lymphocytes arising at the membrane where NO
      activated Ras recruits Raf-1 and culminating in the nucleus where Elk-1 is
      phosphorylated and TNF-alpha messenger RNA is induced. This NO-activated Ras
      mediated signaling pathway may play a critical role in Elk-1-induced
      transcriptional activation of T lymphocytes, host defense and inflammation.

PMID- 10933810
TI  - Effects of 5' leader and 3' trailer structures on pre-tRNA processing by nuclear
      RNase P.
AB  - Eukaryotic transfer RNA precursors (pre-tRNAs) contain a 5' leader preceding the
      aminoacyl acceptor stem and a 3' trailer extending beyond this stem. An early
      step in pre-tRNA maturation is removal of the 5' leader by the endoribonuclease,
      RNase P. Extensive pairing between leader and trailer sequences has previously
      been demonstrated to block RNase P cleavage, suggesting that the 5' leader and 3'
      trailer sequences might need to be separated for the substrate to be recognized
      by the eukaryotic holoenzyme. To address whether the nuclear RNase P holoenzyme
      recognizes the 5' leader and 3' trailer sequences independently, interactions of
      RNase P with pre-tRNA(Tyr) containing either the 5' leader, the 3' trailer, or
      both were examined. Kinetic analysis revealed little effect of the 3' trailer or
      a long 5' leader on the catalytic rate (k(cat)) for cleavage using the various
      pre-tRNA derivatives. However, the presence of a 3' trailer that pairs with the
      5' leader increases the K(m) of pre-tRNA slightly, in agreement with previous
      results. Similarly, competition studies demonstrate that removal of a
      complementary 3' trailer lowers the apparent K(I), consistent with the structure
      between these two sequences interfering with their interaction with the enzyme.
      Deletion of both the 5' and 3' extensions to give mature termini resulted in the
      least effective competitor. Further studies showed that the nuclear holoenzyme,
      but not the B. subtilis holoenzyme, had a high affinity for single-stranded RNA
      in the absence of attached tRNA structure. The data suggest that yeast nuclear
      RNase P contains a minimum of two binding sites involved in substrate
      recognition, one that interacts with tRNA and one that interacts with the 3'
      trailer. Furthermore, base pairing between the 5' leader and 3' trailer hinders
      recognition.

PMID- 10933811
TI  - Region-specific DNA damage by AT-specific DNA-reactive drugs is predicted by drug
      binding specificity.
AB  - Bizelesin and adozelesin are DNA-reactive antitumor drugs that alkylate adenines
      at the 3' ends of their preferred binding sites [5'T(A/T)(4)A3'and 5'(A/T)(3)(
      4)A3', respectively]. We used these drugs to examine the determinants for region
      specific damage of human genomic DNA. The distribution of bizelesin binding
      motifs in several regions analyzed "in silico" correlated well with the
      experimentally determined lesions in these regions assessed by quantitative
      polymerase chain reaction (QPCR) stop assay. In contrast to the typically low
      motif density, clusters of potential bizelesin binding sites were found in the
      matrix-associated regions (MAR domains) of the c-myc and apolipoprotein B (apoB)
      genes. Accordingly, lesions induced by bizelesin in these domains (2.13 and 7.06
      lesions kbp(-1) microM(-1), respectively) markedly exceeded lesions in bulk DNA
      (0.87 lesions kbp(-1) microM(-1)) or in regions with typically low motif density
      (e.g., 0.75 and 0.87 lesions kbp(-1) microM(-1) in a beta-globin gene and c-myc
      origin of replication regions, respectively). Consistent with the more frequent,
      less localized adozelesin motif, actual lesions induced by adozelesin exceeded by
      severalfold lesions by bizelesin in four selected regions (within the c-myc and
      HPRT loci). Whereas adozelesin is likely to affect similar regions as bizelesin,
      adozelesin's more promiscuous binding probably compromises its relative
      specificity for such targets. In contrast, findings for bizelesin provide for the
      first time a proof of principle that a small molecular weight drug can
      preferentially damage specific regions in cellular DNA. Targeting of critical
      repetitive sequences, such as AT-rich MAR domains, which allow for clustering of
      drug binding motif, can be the paradigm for region specificity of small molecular
      weight agents.

PMID- 10933812
TI  - Site-specific topoisomerase I-mediated DNA cleavage induced by nogalamycin: a
      potential role of ligand-induced DNA bending at a distal site.
AB  - Many DNA binding ligands (e.g., nogalamycin, actinomycin D, terbenzimidazoles,
      indolocarbazoles, nitidine, and coralyne) and various types of DNA lesions (e.g.,
      UV dimers, DNA mismatches, and abasic sites) are known to stimulate topoisomerase
      I-mediated DNA cleavage. However, the mechanism(s) by which these covalent and
      noncovalent DNA interactions stimulate topoisomerase I-mediated DNA cleavage
      remains unclear. Using nogalamycin as a model, we have studied the mechanism of
      ligand-induced topoisomerase I-mediated DNA cleavage. We show by both mutational
      and DNA footprinting analyses that the binding of nogalamycin to an upstream site
      (from position -6 to -3) can induce highly specific topoisomerase I-mediated DNA
      cleavage. Substitution of this nogalamycin binding site with a DNA bending
      sequence (A(5)) stimulated topoisomerase I-mediated DNA at the same site in the
      absence of nogalamycin. Replacement of the A(5) sequence with a disrupted DNA
      bending sequence (A(2)TA(2)) significantly reduced the level of topoisomerase I
      mediated DNA cleavage. These results, together with the known DNA bending
      property of nogalamycin, suggest that the nogalamycin-DNA complex may provide a
      DNA structural bend to stimulate topoisomerase I-mediated DNA cleavage.

PMID- 10933813
TI  - Solution structure of monomeric peptide YY supports the functional significance
      of the PP-fold.
AB  - Peptide YY (PYY) belongs to a family of peptides including neuropeptide Y (NPY)
      and pancreatic peptide (PP) that regulate numerous functions through both central
      and peripheral receptors. The solution structure of these peptides is
      hypothesized to be critically important in receptor selectivity and activation,
      based on prior demonstration of a stable tertiary conformation of PP called the
      "PP-fold". Circular dichroism (CD) spectra show a pH-dependent structural
      transition in the pH range 3-4. Thus we describe the tertiary structure of
      porcine PYY in water at pH 5.5, 25 degrees C, and 150 mM NaCl, as determined from
      2D (1)H NMR data recorded at 500 MHz. A constraint set consisting of 396
      interproton distances from NOE data was used as input for distance geometry,
      simulated annealing, and restrained energy minimization calculations in X-PLOR.
      The RMSDs of the 20 X-PLOR-generated structures were 0.71 +/- 0.14 and 1.16 +/-
      0.17 A, respectively, for backbone and heavy atom overlays of residues 1-34. The
      resulting structure consists of two C-terminal helical segments from residues 17
      to 22 and 25 to 33 separated by a kink at residues 23, 24, and 25, a turn
      centered around residues 12-14, and the N-terminus folded near residues 30 and
      31. The well-defined portions of the PYY structure reported here bear a marked
      similarity to the structure of PP. Our findings strongly support the importance
      of the stable folded structure of this family of peptides for binding and
      activation of Y receptor subtypes.

PMID- 10933814
TI  - Conformational changes in the PBX homeodomain and C-terminal extension upon
      binding DNA and HOX-derived YPWM peptides.
AB  - PBX is a member of the three amino acid loop extension (TALE) class of
      homeodomains. PBX binds DNA cooperatively with HOX homeodomain proteins that
      contain a conserved YPWM motif. The amino acids immediately C-terminal to the PBX
      homeodomain increase the affinity of the homeodomain for its DNA site and HOX
      proteins. We have determined the structure of the free PBX homeodomain using NMR
      spectroscopy. Both the PBX homeodomain and the extended PBX homeodomain make
      identical contacts with a 5'-TGAT-3' DNA site and a YPWM peptide. A fourth alpha
      helix, which forms upon binding to DNA, stabilizes the extended PBX structure.
      Variations in DNA sequence selectivity of heterodimeric PBX-HOX complexes depend
      on the HOX partner; however, a comparison of five different HOX-derived YPWM
      peptides showed that each bound to PBX in the same way, differing only in the
      strength of the association.

PMID- 10933815
TI  - Active site dynamics in the lead-dependent ribozyme.
AB  - Conformational dynamics are an important property of ribozymes and other RNA
      molecules but there is currently only limited information on the relationship
      between dynamics and RNA function. A recent structural study of the lead
      dependent ribozyme, known as the leadzyme, showed significant dynamics at the
      active site and indicated that a structural rearrangement is required for the
      reaction to proceed from the ground to the transition state. In this work,
      microsecond-to-millisecond dynamics of the leadzyme are probed by analysis of the
      power dependence of (13)C NMR relaxation times in the rotating frame (T(1)(rho)).
      These results revealed a wide range of conformational dynamics for various
      residues in the leadzyme. For residue A25 in the active site, the power
      dependence of T(1)(rho) yielded an exchange lifetime similar to that previously
      measured by line-shape analysis, and provides an important calibration of this
      T(1)(rho) methodology for probing the dynamics of macromolecules. Strong evidence
      was also found for a previously suggested dynamic network of hydrogen bonds
      stabilizing the GAAA tetraloop motif. Within the active site of the leadzyme,
      internal motions are observed on a wide variety of time scales, suggesting a
      complex landscape of accessible states, and potential correlations between
      observed motions and catalytic function are discussed. These results demonstrate
      that the power dependence of (13)C T(1)(rho) relaxation times provides a valuable
      method for probing dynamics in nucleic acids.

PMID- 10933816
TI  - Mutation of aspartate 804 of Na(+),K(+)-ATPase modifies the cation binding pocket
      and thereby generates a high Na(+)-ATPase activity.
AB  - A series of six different mutants (D804A, D804E, D804G, D804N, D804Q, and D804S)
      of aspartate 804 present in transmembrane segment 6 of the rat Na(+),K(+)-ATPase
      alpha(1)-subunit were prepared and expressed in Sf9 cells by use of the
      baculovirus expression system. In contrast to the wild-type enzyme all mutants
      except D804Q showed a very high Na(+)-ATPase activity, which was hardly further
      stimulated by the addition of K(+). The ATPase activity of the mutants was
      already nearly maximal at 10 microM ATP and most of them could be phosphorylated
      in the absence of Na(+) at pH 6.0 and 21 degrees C, suggesting that they strongly
      prefer the E(1) over the E(2) conformation. However, Na(+) dose-dependently
      lowered the steady-state phosphorylation level, as a consequence of the increased
      affinity for Na(+) in the dephosphorylation reaction of the mutants compared to
      the wild-type enzyme. Conversely, the affinity for K(+) in the dephosphorylation
      reaction was decreased for the mutants as compared to that for the wild-type
      enzyme. When the pH was increased or the temperature was decreased, the
      phosphorylation level of the mutants decreased and the Na(+) activation in the
      phosphorylation reaction became apparent. It is concluded that upon mutation of
      aspartate 804 the affinity of the cation-binding pocket is changed relatively in
      favor of Na(+) instead of K(+), as a consequence of which the enzyme has obtained
      a preference for the E(1) conformation.

PMID- 10933817
TI  - The sorbinil trap: a predicted dead-end complex confirms the mechanism of aldose
      reductase inhibition.
AB  - Kinetic and crystallographic studies have demonstrated that negatively charged
      aldose reductase inhibitors act primarily by binding to the enzyme complexed with
      oxidized nicotinamide dinucleotide phosphate (E.NADP(+)) to form a ternary dead
      end complex that prevents turnover in the steady state. A recent fluorescence
      study [Nakano and Petrash (1996) Biochemistry 35, 11196-11202], however, has
      concluded that inhibition by sorbinil, a classic negatively charged aldose
      reductase inhibitor, results from binding to the enzyme complexed with reduced
      cofactor (E.NADPH) and not binding to E.NADP(+). To resolve this controversy, we
      present transient kinetic data which show unequivocally that sorbinil binds to
      E.NADP(+) to produce a dead-end complex, the so-called sorbinil trap, which
      prevents steady-state turnover in the presence of a saturating concentration of
      aldehyde substrate. The reported fluorescence binding results, which we have
      confirmed independently, are further shown to be fully consistent with the
      proposed sorbinil trap mechanism. Our conclusions are supported by KINSIM
      simulations of both pre-steady-state and steady-state reaction time courses in
      the presence and absence of sorbinil. Thus, while sorbinil binding indeed occurs
      to both E.NADPH and E.NADP(+), only the latter dead-end complex shows significant
      inhibition of the steady-state turnover rate. The effect of tight-binding
      kinetics on the inhibition patterns observed for zopolrestat, another negatively
      charged inhibitor, is further examined both experimentally and with KINSIM, with
      the conclusion that all reported aldose reductase inhibition can be rationalized
      in terms of binding of an alrestatin-like inhibitor at the active site, with no
      need to postulate a second inhibitor binding site.

PMID- 10933818
TI  - Catalase-peroxidase (Mycobacterium tuberculosis KatG) catalysis and isoniazid
      activation.
AB  - Resonance Raman spectra of native, overexpressed M. tuberculosis catalase
      peroxidase (KatG), the enzyme responsible for activation of the antituberculosis
      antibiotic isoniazid (isonicotinic acid hydrazide), have confirmed that the heme
      iron in the resting (ferric) enzyme is high-spin five-coordinate. Difference
      Raman spectra did not reveal a change in coordination number upon binding of
      isoniazid to KatG. Stopped-flow spectrophotometric studies of the reaction of
      KatG with stoichiometric equivalents or small excesses of hydrogen peroxide
      revealed only the optical spectrum of the ferric enzyme with no hypervalent iron
      intermediates detected. Large excesses of hydrogen peroxide generated oxyferrous
      KatG, which was unstable and rapidly decayed to the ferric enzyme. Formation of a
      pseudo-stable intermediate sharing optical characteristics with the porphyrin pi
      cation radical-ferryl iron species (Compound I) of horseradish peroxidase was
      observed upon reaction of KatG with excess 3-chloroperoxybenzoic acid,
      peroxyacetic acid, or tert-butylhydroperoxide (apparent second-order rate
      constants of 3.1 x 10(4), 1.2 x 10(4), and 25 M(-1) s(-1), respectively).
      Identification of the intermediate as KatG Compound I was confirmed using low
      temperature electron paramagnetic resonance spectroscopy. Isoniazid, as well as
      ascorbate and potassium ferrocyanide, reduced KatG Compound I to the ferric
      enzyme without detectable formation of Compound II in stopped-flow measurements.
      This result differed from the reaction of horseradish peroxidase Compound I with
      isoniazid, during which Compound II was stably generated. These results
      demonstrate important mechanistic differences between a bacterial catalase
      peroxidase and the homologous plant peroxidases and yeast cytochrome c
      peroxidase, in its reactions with peroxides as well as substrates.

PMID- 10933819
TI  - Spectroscopic comparison of the heme active sites in WT KatG and its S315T
      mutant.
AB  - KatG, the catalase-peroxidase from Mycobacterium tuberculosis, has been
      characterized by resonance Raman, electron spin resonance, and visible
      spectroscopies. The mutant KatG(S315T), which is found in about 50% of isoniazid
      resistant clinical isolates, is also spectroscopically characterized. The
      electron spin resonance spectrum of ferrous nitrosyl KatG is consistent with a
      proximal histidine ligand. The Fe-His stretching vibration observed at 244 cm(-1)
      for ferrous wild-type KatG and KatG(S315T) confirms the imidazolate character of
      the proximal histidine in their five-coordinate high-spin complexes. The ferrous
      forms of wild-type KatG and KatG(S315T) are mixtures of six-coordinate low-spin
      and five-coordinate high-spin hemes. The optical and resonance Raman signatures
      of ferric wild-type KatG indicate that a majority of the heme exists in a five
      coordinate high-spin state, but six-coordinate hemes are also present. At room
      temperature, more six-coordinate low-spin heme is observed in ferrous and ferric
      KatG(S315T) than in the WT enzyme. While the nature of the sixth ligand of LS
      ferric wild-type KatG is not completely clear, visible, resonance Raman, and
      electron spin resonance data of KatG(S315T) indicate that its sixth ligand is a
      neutral nitrogen donor. Possible effects of these differences on enzyme activity
      are discussed.

PMID- 10933820
TI  - Formation of a bis(histidyl) heme iron complex in manganese peroxidase at high pH
      and restoration of the native enzyme structure by calcium.
AB  - Manganese peroxidase (MnP) from Phanerochaete chrysosporium undergoes a pH
      dependent conformational change evidenced by changes in the electronic absorption
      spectrum. This high- to low-spin alkaline transition occurs at approximately 2 pH
      units lower in an F190I mutant MnP when compared to the wild-type enzyme. Herein,
      we provide evidence that these spectral changes are attributable to the formation
      of a bis(histidyl) heme iron complex in both proteins at high pH. The resonance
      Raman (RR) spectra of both ferric proteins at high pH are similar, indicating
      similar heme environments in both proteins, and resemble that of ferric
      cytochrome b(558), a protein that contains a bis-His iron complex. Upon reduction
      with dithionite at high pH, the visible spectra of both the wild-type and F190I
      MnP exhibit absorption maxima at 429, 529, and 558 nm, resembling the absorption
      spectrum of ferrous cytochrome b(558). RR spectra of the reduced wild-type and
      F190I mutant proteins at high pH are also similar to the RR spectrum of ferrous
      cytochrome b(558), further suggesting that the alkaline low-spin species is a
      bis(histidyl) heme derivative. No shift in the low-frequency RR bands was
      observed in 75% (18)O-labeled water, indicating that the low-spin species is most
      likely not a hydroxo-heme derivative. Electronic and RR spectra also indicate
      that addition of Ca(2+) to either the ferric or ferrous enzymes at high pH
      completely restores the high-spin pentacoordinate species. Other divalent metals,
      such as Mn(2+), Mg(2+), Zn(2+), or Cd(2+), do not restore the enzyme under the
      conditions studied.

PMID- 10933821
TI  - Nonhydrolyzable diubiquitin analogues are inhibitors of ubiquitin conjugation and
      deconjugation.
AB  - A series of nonhydrolyzable ubiquitin dimer analogues has been synthesized and
      evaluated as inhibitors of ubiquitin-dependent processes. Dimer analogues were
      synthesized by cross-linking ubiquitin containing a terminal cysteine (G76C) to
      ubiquitin containing cysteine at position 11 ((76-11)Ub(2)), 29 ((76-29)Ub(2)),
      48 ((76-48)Ub(2)), or 63 ((76-63)Ub(2)). A head-to-head dimer of cysteine G76C
      ((76-76)Ub(2)) served as a control. These analogues are mimics of the different
      chain linkages observed in natural polyubiquitin chains. All analogues showed
      weak inhibition toward the catalytic domain of UCH-L3 and a UBP pseudogene. In
      the absence of ubiquitin, isopeptidase T was inhibited only by the dimer linked
      through residue 29. In the presence of 0.5 microM ubiquitin, isopeptidase T was
      inhibited by several of the dimer analogues, with the (76-29)Ub(2) dimer
      exhibiting a K(i) of 1.8 nM. However, USP14, the human homologue of yeast Ubp6,
      was not inhibited at the concentrations tested. Some analogues of ubiquitin dimer
      also acted as selective inhibitors of conjugation and deconjugation of ubiquitin
      catalyzed by reticulocyte fraction II. (76-76)Ub(2) and (76-11)Ub(2) did not
      inhibit the conjugation of ubiquitin, while (76-29)Ub(2), (76-48)Ub(2), and (76
      63)Ub(2) were potent inhibitors of conjugation. This specificity is consistent
      with the known ability of cells to form K29-, K48-, and K63-linked polyubiquitin
      chains. While (76-11)Ub(2), (76-29)Ub(2), and (76-63)Ub(2) inhibited release of
      ubiquitin from a pool of total conjugates, (76-48)Ub(2) and (76-76)Ub(2) showed
      no significant inhibition. Isopeptidase T was shown to specifically disassemble
      two conjugates (assumed to be di- and triubiquitin with masses of 26 and 17 kDa)
      formed in the reticulocyte lysate system. This activity was inhibited
      differentially by all dimer analogues. The inhibitor selectivity for
      deconjugation of the 26 and 17 kDa conjugates was similar to that observed for
      isopeptidase T. The observations suggest that these two conjugated proteins of
      the reticulocyte lysate are specific substrates for isopeptidase T in lysates.

PMID- 10933822
TI  - Accelerated accumulation of amyloid beta proteins on oxidatively damaged lipid
      membranes.
AB  - The fully developed lesion of Alzheimer's Disease is a dense plaque composed of
      fibrillar amyloid beta-proteins with a characteristic and well-ordered beta-sheet
      secondary structure. Because the incipient lesion most likely develops when these
      proteins are first induced to form beta-sheet secondary structure, it is
      important to understand factors that induce amyloid beta-proteins to adopt this
      conformation. In this investigation we used a novel form of infrared spectroscopy
      that can characterize the conformation, orientation, and rate of accumulation of
      the protein on various lipid membranes to determine whether oxidatively damaged
      phospholipid membranes induce the formation of beta-sheet secondary structure in
      a 42-residue amyloid beta-protein. We found that membranes containing oxidatively
      damaged phospholipids accumulated amyloid beta-protein significantly faster than
      membranes containing only unoxidized or saturated phospholipids. Accelerated
      accumulation was also seen when 3 mol % G(M1) ganglioside was incorporated into a
      saturated phosphatidylcholine membrane. The accumulated protein more completely
      adopted a beta-sheet conformation on oxidized membranes, and the plane of the
      beta-sheet was oriented parallel to the plane of the membrane. These results
      indicate that oxidatively damaged phospholipid membranes promote beta-sheet
      formation by amyloid beta-proteins, and they suggest a possible role for lipid
      peroxidation in the pathogenesis of Alzheimer's Disease.

PMID- 10933823
TI  - Dependence of apparent viscosity on mycelial morphology of Streptomyces fradiae
      culture in various nitrogen sources.
AB  - To examine what causes increased viscosity in culture broth in Streptomyces
      fradiae culture, various natural nitrogen sources were investigated.
      Extracellular protease activity increased with culture time and decomposed the
      natural nitrogen source into amino acids. In the case of gluten meal, after a
      culture time of 5 d, concentrations of glutamic acid and aspartic acid had
      increased to 600 and 200 mg/L, respectively, which were about 3- and 2-fold as
      high as levels in cultures under similar conditions using Pharmamedia. For
      various amino acids tested, the addition of glutamic acid or aspartic acid
      mixture to the culture medium raised the apparent viscosity to its highest
      demonstrated value, 260 mPa.s after 5 d of culture, which was 3-fold higher than
      without amino acids. Consumption of the decomposed glutamic acid and aspartic
      acid was dependent on the activities of glutamate dehydrogenase and aspartate
      aminotransferase, respectively. When ammonium ion was used as the nitrogen
      source, cell concentration reached 1.75 g/L measured as an intracellular nucleic
      acid concentration, which was about 2.3-fold higher than that with any other
      natural nitrogen source. However, apparent viscosity was only 75 mPa.s, a value
      one-third that of the amino acid mixture, and 70% of the pellets were bigger than
      1.2 x 10(4) microm(2). In the case of gluten meal or the amino acid mixture,
      pellets bigger than 1.2 x 10(4) microm(2) comprised only 8%. This demonstrates
      that consumption of some amino acids affected the formation of filamentous
      morphology, which caused an increase in the apparent viscosity of the culture
      broth, and the apparent viscosity was not caused by the mycelial concentration
      but the mycelial morphology.

PMID- 10933824
TI  - Color and toxicity removal following tyrosinase-catalyzed oxidation of phenols.
AB  - The products of phenol oxidation catalyzed by mushroom tyrosinase (polyphenol
      oxidase, EC 1.14.18.1) were assessed in terms of their residual color and
      toxicity. The addition of aluminum sulfate had little effect on the removal of
      colored products from phenol solutions treated with tyrosinase. Although chitosan
      was used successfully to remove the color when added before the reaction
      initiation or after the reaction completion, the required dose of chitosan was
      lower when it was added after the reaction. In this case, the minimum doses of
      chitosan required to achieve 90% color removal were proportional to the logarithm
      of the initial concentration of phenol. The color removal induced by chitosan
      addition appeared to be the result of chemical interaction followed by a
      coagulation mechanism. All treated solutions of phenol and chlorophenols, except
      2,4-dichlorophenol, had substantially lower toxicities than their corresponding
      initial toxicities, as measured using the Microtox assay. Chitosan addition
      significantly enhanced the reduction in toxicity. The toxicities of the phenol
      solutions treated with tyrosinase were markedly lower than previously reported
      toxicities of solutions treated with peroxidase enzymes.

PMID- 10933825
TI  - Dry-grind process for fuel ethanol by continuous fermentation and stripping.
AB  - Conversion of a high-solids saccharified corn mash to ethanol by continuous
      fermentation and stripping was successfully demonstrated in a pilot plant
      consuming 25 kg of corn per day. A mathematical model based on previous pilot
      plant results accurately predicts the specific growth rate obtained from these
      latest results. This model was incorporated into a simulation of a complete dry
      grind corn-to-ethanol plant, and the cost of ethanol production was compared with
      that of a conventional process. The results indicate a savings of $0.03 per
      gallon of ethanol produced by the stripping process. The savings with stripping
      result from the capacity to ferment a more concentrated corn mash so there is
      less water to remove downstream.

PMID- 10933826
TI  - Enhancement of kasugamycin production by pH shock in batch cultures of
      Streptomyces kasugaensis.
AB  - Biosynthesis of kasugamycin could be greatly enhanced by applying a
      nonnutritional stress of pH shock, that is, sequential pH changes from a neutral
      pH to an acidic condition and then back to the neutral condition. During the
      acidic period, cell growth decreased to nil. After recovery of the neutral
      condition, the cell growth resumed after a time lag concurrently with the
      biosynthesis of kasugamycin at a greatly enhanced rate compared with the control
      case without a pH shock. In a series of experiments performed to identify the
      optimal length of pH shock, four different lengths (6, 12, 24, and 48 h) of pH
      shock were applied. The best result was obtained when pH shock was applied for 24
      h, with kasugamycin productivity approximately 7-fold higher than that of the
      control.

PMID- 10933827
TI  - Precursor-directed biosynthesis of 6-deoxyerythronolide B analogs in Streptomyces
      coelicolor: understanding precursor effects.
AB  - A fermentation process employing precursor-directed biosynthesis is being
      developed for the manufacture of 6-deoxyerythronolide B (6-dEB) analogues.
      Through a plasmid-based system in Streptomyces coelicolor, 6-dEB synthesis is
      catalyzed by 6-dEB synthase (DEBS). 6-dEB synthesis is abolished by inactivation
      of the ketosynthase (KS) 1 domain of DEBS but can be restored by providing
      synthetic activated diketides. Because of its inherent catalytic flexibility, the
      KS1-deficient DEBS is capable of utilizing unnatural diketides to form various 13
      substituted 6-dEBs. Here we characterize process variables associated with
      diketide feeding in shake-flask experiments. 13-R-6-dEB production was found to
      depend strongly on diketide feed concentrations, on the growth phase of cultures
      at feeding time, and on the R-group present in the diketide moiety. In all cases
      a major portion of the fed diketides was degraded by the cells.

PMID- 10933828
TI  - Expression of single chain antibodies (ScFvs) for c-myc oncoprotein in
      recombinant Escherichia coli membranes by using the ice-nucleation protein of
      Pseudomonas syringae.
AB  - The ice nucleation protein (INP) is a glycosyl phosphatidylinositol anchored
      outer membrane protein found in certain Gram-negative bacteria. In this study,
      the INP from Pseudomonas syringae was applied as a fusion partner with the single
      chain antibody fragment (ScFv) against the human oncoprotein c-myc. Two new
      plasmids pNinaZ-myc and pNinaZScFv-BsaA1 were constructed and cloned into
      Escherichia coli JM109. The expression of the fusion protein was successfully
      demonstrated in the cloned cells. The fusion proteins had no effect on the
      viability of the host cells. Ice nucleation activity measurements and flow
      cytometry studies were followed to investigate the membrane expression of the
      fusion protein.

PMID- 10933829
TI  - Production of D-amino acid using whole cells of recombinant Escherichia coli with
      separately and coexpressed D-hydantoinase and N-carbamoylase.
AB  - We developed a fully enzymatic process employing D-hydantoinase and N
      carbamoylase for the production of D-amino acid from 5'-monosubstituted
      hydantoin. For the comparison of the reaction systems using two sequential
      enzymes, D-hydantoinase of Bacillus stearothermophilus SD1 and N-carbamoyl-D
      amino acid amidohydrolase (N-carbamoylase) of Agrobacterium tumefaciens NRRL
      B11291 were separately expressed in each host cell and coexpressed in the same
      host cell. A high level and constitutive expression of both enzymes in
      Escherichia coli in a soluble form was achieved using a promoter derived from B.
      stearothermophilus SD1. The expression levels of both enzymes ranged from 17% to
      23% of the total soluble protein, depending on the expression system. In the case
      of employing separately expressed enzymes, the product yield of D
      hydroxyphenylglycine from D,L-p-hydroxyphenylhydantoin and productivity were 71%
      and 2.57 mM/g-cell/h in 15 h, respectively. The accumulation of N-carbamoyl-D
      hydroxyphenylglycine was significant over the reaction time. On the other hand,
      use of coexpressed enzymes resulted in 98% product yield of D
      hydroxyphenylglycine in 15 h, minimizing the level of intermediates in the
      reaction mixture. The productivity of coexpressed whole cell reaction was
      estimated to be 6.47 mM/g-cell/h in 15 h. The coexpressed system was tested for
      an elevated concentration of D,L-p-hydroxyphenylhydantoin, and efficient
      production can be achieved.

PMID- 10933830
TI  - A recombinant lipoprotein antigen against Lyme disease expressed in E. coli:
      fermentor operating strategies for improved yield.
AB  - Decorin-binding lipoprotein, lpp-DBP, a bacterial surface adhesin, shows promise
      as a vaccine against Lyme disease. It is expressed in recombinant E. coli as an
      undesirable 20.5 KDa apoprotein that is subsequently lipidated in vivo to the
      desired 22 KDa lpp-DBP form. This study defines fermentation conditions for
      maximizing lpp-DBP yield. Super broth medium, a low post-induction temperature
      (30 degrees C), and a glucose feed based on dissolved oxygen resulted in high lpp
      DBP yield and minimized apoprotein formation. Since cells lysed within 2-3 h
      after induction, the cell yield was maximized by growing cells to high cell
      density prior to induction. Compared to a glucose feed based on maintaining a
      constant fermentor glucose concentration (Glucose-Stat), feeding based on
      maintaining a constant dissolved oxygen level (DO-Stat) improved yields. Also, a
      dissolved oxygen level of 60% (air saturation) was best, as no product
      degradation was detected by Western blotting and SDS-PAGE. Acetic acid levels
      under both modes of glucose feed were sufficiently low, and no adverse growth
      effects were observed.

PMID- 10933831
TI  - Reactivity of 3-HBA-6-hydroxylase with diethylpyrocarbonate and N
      bromosuccinimide: effect of chemical modifications on kinetic and spectral
      properties of the enzyme.
AB  - The rapid inactivation of 3-HBA-6-hydroxylase by 100 microM diethylpyrocarbonate
      or 40 microM N-bromosuccinimide and protection offered by the substrate, 3
      hydroxybenzoate, against these chemical modifications implicate the involvement
      of histidine and tryptophan in the catalytic activity of the enzyme. Inactivation
      of the enzyme by diethylpyrocarbonate followed pseudo-first-order kinetics, and
      an "n" value of 1.3 was obtained. Inactivation of the enzyme by N
      bromosuccinimide was instantaneous and failed to follow pseudo-first-order
      kinetics. Distinct and incremental changes in the UV absorption, emission
      fluorescence, and near UV-CD spectra of the enzyme upon its titration with
      increasing concentrations of diethylpyrocarbonate or N-bromosuccinimide may be
      ascribed to modification and/or changes in the microenvironment of aromatic amino
      acid residue(s) such as tryptophan in the enzyme.

PMID- 10933832
TI  - Characterization and catalytic property of surfactant-laccase complex in organic
      media.
AB  - The oxidation of o-phenylenediamine catalyzed in anhydrous organic solvents by
      surfactant-laccase complex was investigated. The complex was prepared by
      utilizing a novel preparation technique in water-in-oil (W/O) emulsions. The
      surfactant-laccase complex effectively catalyzed the oxidation reaction in
      various dry organic solvents, while laccase, lyophilized from an aqueous buffer
      solution in which its activity was optimized, exhibited no catalytic activity in
      nonaqueous media. To optimize the preparation and reaction conditions for the
      surfactant-enzyme complexes, we examined the effects of pH in the water pool of
      W/O emulsions, the concentration of enzyme and surfactant at the preparation
      stage, and the nature of organic solvents at the reaction stage on the laccase
      activity in organic media. Surfactant-laccase complex showed a strong pH
      dependent catalytic activity in organic media. Its optimum activity was obtained
      when the complex was prepared at a pH of about 3. Interestingly, native laccase
      in an aqueous buffer solution exhibited an optimum activity at the same pH of 3.
      The optimum preparation conditions of surfactant-laccase complex were [laccase] =
      0.8 mg/mL and [surfactant] = 10 mM, and the complex showed the highest catalytic
      activity in toluene among nine anhydrous organic solvents. The effect of a
      cosolubilized mediator (1-hydroxybenzotriazole (HBT)) on the reaction was also
      investigated. The addition of HBT at the preparation stage of the enzyme complex
      did not accelerate the catalytic reaction because HBT was converted to an
      inactive benzotriazole (BT) by laccase. However, the addition of HBT at the
      reaction stage enhanced the catalytic performance by a factor of five compared to
      that without HBT.

PMID- 10933833
TI  - Enzymatic synthesis of alpha-butylglucoside linoleate in a packed bed reactor for
      future pilot scale-up.
AB  - The enzymatic synthesis of a mixture of unsaturated fatty acid alpha
      butylglucoside esters, containing more than 60% alpha-butylglucoside linoleate,
      was achieved through lipase-catalyzed esterification. The continuous evaporation
      under reduced pressure of the water produced enabled substrate conversions
      greater than 95% to be reached. Two immobilized lipases from Candida antarctica
      (Chirazyme L2, c.-f., C2) and Rhizomucor miehei (Chirazyme L9, c.-f.) were
      compared in stirred batch and packed bed configurations. When the synthesis was
      carried out in stirred batch mode, C. antarctica lipase appeared to be of greater
      interest than the R. miehei enzyme in terms of stability and regioselectivity.
      Surprisingly, a change in the process design to a packed bed configuration
      enabled the stability of R. miehei lipase to be significantly improved, while the
      C. antarctica lipase efficiency to synthesize unsaturated fatty acid alpha
      butylglucoside esters was slightly decreased. Water content in the
      microenvironment of the biocatalyst was assumed to be responsible for such
      changes. When the process is run in stirred batch mode, the conditions used
      promote the evaporation of the essential water surrounding the enzyme, which
      probably leads to R. miehei lipase dehydration. In contrast, the packed bed
      design enabled such water evaporation in the microenvironment of the biocatalyt
      to be avoided, which resulted in a tremendous improvement of R. miehei lipase
      stability. However, C. antarctica lipase led to the formation of 3% diesters,
      whereas the final percentage of diesters reached 21% when R. miehei enzyme was
      used as biocatalyst. A low content of diesters is of greater interest in terms of
      alpha-butylglucoside linoleate application as linoleic acid carrier, and
      therefore the enzyme choice will have to be made depending on the properties
      expected for the final product.

PMID- 10933835
TI  - Regioselective enzymatic diol esterification in batch and fixed-Bed adsorptive
      reactors: experiments and modeling.
AB  - The dynamic behavior of batch and fixed-bed adsorptive reactors is studied for
      the enzyme-catalyzed regioselective esterification of propionic acid and 2-ethyl
      1,3-hexanediol in hexane. The reaction is equilibrium-limited with an apparent
      equilibrium constant of 0.6 +/- 0.1 at 22 degrees C. Moreover, accumulation of
      water produced in the reaction onto the biocatalyst causes a decrease in the
      catalytic activity. As a result, improvements in both reaction rate and final
      conversion can be achieved by operating in an adsorptive-reactor mode. Control of
      water in the reactor is achieved with a catalytically inert ion-exchange resin in
      Na-form. The resin prevents an excessive accumulation of water on the biocatalyst
      and reduces equilibrium limitations. The thermodynamic activity of water is
      identified as a key parameter for the design of such reactors. A mathematical
      model capable of predicting the water activity as a function of the varying
      concentrations of reactants and products is thus developed and found to
      successfully predict the experimental behavior observed in laboratory reactors.
      Substantial improvements in performance predicted by the model are seen
      experimentally in batch reactions and during the transient operation of
      continuous-flow fixed-bed reactors combining adsorptive and catalytic functions.

PMID- 10933834
TI  - Production of alpha-galactosyl epitopes via combined use of two recombinant whole
      cells harboring UDP-galactose 4-epimerase and alpha-1,3-galactosyltransferase.
AB  - alpha-Galactosyl epitopes (or alpha-Gal, oligosaccharides with a terminal
      Galalpha1,3Gal sequence) are a class of biologically important oligosaccharides
      in great demand in bulk quantities for basic and clinical studies on preventing
      hyperacute rejection in pig-to-primate organ xenotransplantation. A truncated
      bovine alpha-1, 3-galactosyltransferase, the key enzyme responsible for the
      biosynthesis of the terminal structure of alpha-Gal, was cloned and overexpressed
      previously. The acceptor specificity was further studied in the present paper,
      and lactose and galactose derivatives were found to be good acceptors. To develop
      a more proficient reaction process, we report herein an example of an efficient
      enzymatic synthesis of alpha-Gal oligosaccharides catalyzed by the combination of
      two recombinant Escherichia coli whole cells harboring the genes of a UDP
      galactose 4-epimerase and the alpha-1, 3-galactosyltransferase, respectively.
      Using lactosyl azide (LacN(3)) as the acceptor for the glycosyltransferase, the
      combined use of the two recombinant cells efficiently produced alpha-Gal epitope
      Gal alpha1,3LacN(3) in 60-68% yield.

PMID- 10933836
TI  - Improving the cytochrome P450 enzyme system for electrode-driven biocatalysis of
      styrene epoxidation.
AB  - Cytochrome P450 enzymes catalyze a vast array of oxidative and reductive
      biotransformations that are potentially useful for industrial and pharmaceutical
      syntheses. Factors such as cofactor utilization and slow reaction rates for
      nonnatural substrates limit their large-scale usefulness. This paper reports
      several improvements that make the cytochrome P450cam enzyme system more
      practical for the epoxidation of styrene. NADH coupling was increased from 14 to
      54 mol %, and product turnover rate was increased from 8 to 70 min(-1) by
      introducing the Y96F mutation to P450cam. Styrene and styrene oxide mass balance
      determinations showed different product profiles at low and high styrene
      conversion levels. For styrene conversion less than about 25 mol %, the
      stoichiometry between styrene consumption and styrene oxide formation was 1:1. At
      high styrene conversion, a second doubly oxidized product, alpha
      hydroxyacetophenone, was formed. This was also the exclusive product when Y96F
      P450cam acted on racemic, commercially available styrene oxide. The alpha
      hydroxyacetophenone product was suppressed in reactions where styrene was present
      at saturating concentrations. Finally, styrene epoxidation was carried out in an
      electroenzymatic reactor. In this scheme, the costly NADH cofactor and one of the
      three proteins (putidaredoxin reductase) are eliminated from the Y96F P450cam
      enzyme system.

PMID- 10933837
TI  - A study of mass transfer kinetics in an enantiomeric separation system using a
      polymeric imprinted stationary phase.
AB  - Chromatographic data pertaining to the enantioseparation of L- and D
      phenylalanine anilide (PA) on a polymeric stationary phase imprinted with L-PA
      were studied from the viewpoints of phase equilibrium, mass transfer kinetics,
      and the thermodynamic properties of this enantiomeric separation system. The
      concentration dependence of the lumped mass transfer rate coefficient (k(m,L))
      previously published was analyzed to obtain new information concerning the mass
      transfer characteristics in this chiral separation system. It was shown that
      intraparticle diffusion contributed much more to k(m,L) than
      adsorption/desorption. The positive concentration dependence of k(m,L) seemed to
      be interpreted by considering that of the surface diffusion coefficient, itself
      explained by the heterogeneous surface model. The characteristic features of the
      phase equilibrium, the mass transfer kinetics, and the thermodynamics of the
      enantiomeric separation system probably result from the adsorption energy
      distribution on the surface of the imprinted phase having an exponential decay.

PMID- 10933838
TI  - Stability of subtilisin and lysozyme under high hydrostatic pressure.
AB  - The stabilities of subtilisin and lysozyme under hydrostatic pressures up to 200
      MPa were investigated for up to 7 days at 25 degrees C. Methods were chosen to
      assess changes in tertiary and secondary protein structure as well as aggregation
      state. Tertiary structure was monitored in situ with second derivative UV
      spectroscopy and after pressure treatment by dynamic light scattering and second
      derivative UV spectroscopy. Secondary structure and potential secondary
      structural changes were characterized by second derivative FTIR spectroscopy.
      Changes in aggregation state were assessed using dynamic light scattering.
      Additionally, protein concentration balances were carried out to detect any loss
      of protein as a function of pressure. For the conditions tested, neither protein
      shows measurable changes in tertiary or secondary structure or signs of
      aggregation. Lysozyme concentration balances show no dependence on pressure.
      Subtilisin concentration balances at high protein concentration (4 mg/mL and
      higher) do not show pressure dependence. However, the concentration balances
      carried out at 0.4 mg/mL show a clear sign of pressure dependence. These results
      may be explained by protein interaction with the vial surface and appear to be
      rate limited by the equilibrium between active and inactive protein on the
      surface. Pressure increases protein loss, and the estimated partial molar volume
      change between the two states is estimated to be -20 +/- 10 mL/mol.

PMID- 10933840
TI  - GC-MS analysis of amino acids rapidly provides rich information for isotopomer
      balancing.
AB  - Gas chromatography-mass spectrometry (GC-MS) is a rapid method that provides rich
      information on isotopomer distributions for metabolic flux analysis. First, we
      established a fast and reliable experimental protocol for GC-MS analysis of amino
      acids from total biomass hydrolyzates, and common experimental pitfalls are
      discussed. Second, a suitable interface for the use of mass isotopomer data is
      presented. For this purpose, a general, matrix-based correction procedure that
      accounts for naturally occurring isotopes is introduced. Simulated and
      experimentally determined mass distributions of unlabeled amino acids showed a
      deviation of less than 3% for 89% of the analyzed fragments. Third, to
      investigate general properties of GC-MS-based isotopomer balancing, altered flux
      ratios through glycolysis and pentose phosphate pathway and/or exchange fluxes
      were simulated. Different fluxes were found to exert specific and significant
      influence on the mass isotopomer distributions, thus indicating that GC-MS data
      contain valuable information for metabolic flux analysis. Fourth, comparison of
      different methods revealed that GC-MS analysis provides the largest number of
      independent constraints on amino acid isotopomer abundance, followed by
      correlation spectroscopy and fractional enrichment analysis by nuclear magnetic
      resonance.

PMID- 10933839
TI  - Use of UV absorbance To monitor furans in dilute acid hydrolysates of biomass.
AB  - A simple method based on UV spectra was developed for the estimation of total
      furans (furfural and hydroxymethylfurfural) in hemicellulose hydrolysates. UV
      spectra of hemicellulose hydrolysate contained a single dominant peak at around
      278 nm. Approximately two-thirds of this peak can be attributed to furan
      absorbance (furfural and hydroxymethylfurfural). At 284 nm, both furfural and
      hydroxymethylfurfural have equal absorbance on a weight basis. A comparison of
      HPLC determinations for different samples of hydrolysate was used to develop a
      simple equation that allows the accurate prediction of total furans based on the
      difference in absorbance at 284 and 320 nm. This method may prove useful for
      quality control applications during the production of biomass syrups using a
      dilute acid hydrolysis process and during treatments for the amelioration of
      toxins. Although furans represent only a portion of the toxins present in
      hemicellulose hydrolysates, the abundance of furans appears to serve as a useful
      marker to predict relative toxicity.

PMID- 10933842
TI  - High cell density culture of Yarrowia lipolytica using a one-step feeding
      process.
AB  - Yarrowia lipolytica is a potentially useful host for heterologous protein
      production. To develop an efficient culture method for high cell density
      cultivation and heterologous gene expression of Y. lipolytica, the effects of
      medium components and their concentrations on the growth of Y. lipolytica have
      been investigated. Addition of yeast extract to the culture media was found to
      significantly reduce the long lag phase encountered when Y. lipolytica was
      cultivated in synthetic culture media containing high concentrations of glycerol.
      Therefore, by enriching with 0.3% yeast extract the synthetic culture medium
      containing 15% glycerol, we could cultivate Y. lipolytica up to 83 g/L dry cell
      weight in a batch culture. Furthermore, over 100 g/L and 88 units/mL of rice
      alpha-amylase activity were obtained in less than 50 h with a one-step feeding
      process in which a recombinant Y. lipolytica expressing rice alpha-amylase was
      cultivated in the 10% glycerol medium enriched with 0.3% yeast extract and fed
      only once with the concentrated feeding medium (60% glycerol). The easy
      cultivation of recombinant Y. lipolytica to a high cell density may strengthen
      its position as a host for heterologous protein production.

PMID- 10933841
TI  - Influence of baculovirus-host cell interactions on complex N-linked glycosylation
      of a recombinant human protein.
AB  - The conditions required for mammalian-type complex N-linked glycosylation of
      human proteins produced in insect cells with the baculovirus expression vector
      system were investigated. Marked alterations to N-linked glycosylation of human
      placental secreted alkaline phosphatase (SEAP) were observed with different
      baculovirus species, insect cell lines, and cell culture media. When a
      recombinant Autographa californica nucleopolyhedrovirus (AcMNPV) was used to
      produce SEAP in Trichoplusia ni (Tn-4h) cells cultured in serum-free medium,
      structural analyses indicated <1% hybrid and no complex oligosaccharides attached
      to SEAP, a typical result with the baculovirus expression vector system. However,
      when fetal bovine serum was added to the culture medium, 48 +/- 4% of the
      oligosaccharides were hybrid or complex (but asialylated) glycans. When a
      recombinant T. ni nucleopolyhedrovirus (TnSNPV) was similarly used to express
      SEAP in Tn-4h cells cultured in serum-containing medium, only 24 +/- 3% of the
      glycans contained terminal N-acetylglucosamine and/or galactose residues. In
      contrast, SEAP produced in Sf9 cells grown in serum-containing medium with AcMNPV
      contained <1% hybrid oligosaccharides and no complex oligosaccharides. The
      results illustrate that baculovirus type, host cell type, and the growth medium
      all have a strong influence on the glycosylation pathway in insect cells,
      resulting in significant alterations in structures and relative abundance of N
      linked glycoforms. Although the addition of sialic acid residues to the SEAP
      glycans was not detected, possible approaches to obtain sialylated glycans are
      discussed.

PMID- 10933843
TI  - Selective flocculation and precipitation for the improvement of virus-like
      particle recovery from yeast homogenate.
AB  - The purification of an intracellular product from a complex mixture of
      contaminants after cell disruption is a common problem in processes downstream of
      fermentation systems. This is particularly challenging for the recovery of
      particulate (80 nm in diameter) multimeric protein products, named virus-like
      particles (VLPs), from cell debris and other intracellular components. Selective
      flocculation for debris removal followed by selective precipitation of the target
      protein can be used as a preclarification step to aid purification. In this
      paper, selective borax flocculation of cell debris in yeast homogenate, followed
      by selective poly(ethylene glycol) precipitation of VLPs are defined with a view
      to demonstrating their potential in aiding the initial clarification stages of
      the purification sequence. The translation from laboratory scale to pilot scale
      operation is addressed, demonstrating the challenge of scale-up of solid-liquid
      separation stages for biological particle processing.

PMID- 10933844
TI  - Nutrient medium optimization for rosmarinic acid production by Lavandula vera MM
      cell suspension.
AB  - The overall effect of NH(4)NO(3), KNO(3), and KH(2)PO(4) on the biosynthesis of
      rosmarinic acid and cell biomass by Lavandula vera MM cell suspension was studied
      by the method of the full factor experiment. Polynomial regression models were
      elaborated to give a quantitative description of the processes of biosynthesis of
      rosmarinic acid (Y(1)) and cell biomass (Y(2)) as a result of the variation of
      the concentration of NH(4)(+), 0.09 g/L < or = X(1) < or = 0. 23 g/L; NO(3)(-),
      2.44 g/L < or = X(2) < or = 3.02 g/L; and KH(2)PO(4), 0. 170 < or = X(3) < or =
      0.425 g/L. Optimization procedures according to the modified Simplex method
      allowed us to establish the optimal conditions for the biosynthesis of rosmarinic
      acid by Lavandula vera MM: X(1*) = 0.09 g/L; X(2*) = 3.02 g/L, and X(3*) = 0.170
      g/L, where Y(1)max = 1786.74 mg/L (27 times higher compared with the cultivation
      in the standard Linsmayer-Skoog medium). As a result, modified ingredients of the
      Linsmayer-Skoog nutrient medium were applied for the cultivation of Lavandula
      vera MM to achieve a maximum yield of rosmarinic acid.

PMID- 10933845
TI  - Design of a molecular chaperone-assisted protein folding bioreactor.
AB  - Escherichia coli molecular chaperone GroEL and co-chaperone GroES are well known
      to assist the folding/refolding of a diverse range of substrate proteins. Despite
      this, there have been relatively few reports of the GroEL/GroES molecular
      chaperone system being used as a biotechnology tool for protein
      folding/refolding. In this paper, a solution-phase protein folding bioreactor is
      described that involves the complete GroEL/GroES system. The main features of
      this bioreactor are the use of a stirred-cell concentrator fitted with a 100 kDa
      molecular weight cutoff membrane and an attached buffer reservoir. This
      bioreactor system was used successfully for assisted-batch refolding of
      guanidinium chloride (Gu-HCl) unfolded mitochondrial malate dehydrogenase (mMDH).
      We believe that protein folding bioreactor systems of this type could have wide
      potential utility for the folding/refolding of unfolded protein substrates.

PMID- 10933846
TI  - Recovery of poly(3-hydroxybutyrate) from coagulated Ralstonia eutropha using a
      chemical digestion method.
AB  - For economic recovery of poly(3-hydroxybutyrate) (PHB) from culture broths of
      Ralstonia eutropha containing PHB, Al-based and Fe-based coagulants were used in
      the pretreatment step. The coagulated cells were then separated by
      centrifugation, and PHB was extracted by chemical digestion with a sodium
      hypochlorite/chloroform dispersion solution. The practical upper limits of dosage
      were found to be 1, 500 mg-Al/L and 1,000 mg-Fe/L, respectively, for Al- and Fe
      based coagulants. When the harvested cells were treated with a 50% sodium
      hypochlorite/chloroform dispersion solution, PHB recovery and purity were 90-94%
      and 98-99%, respectively. The influence of the use of coagulants on the PHB
      recovery process was found to be insignificant. Despite the residual Al and Fe in
      the recovered PHB (less than 450 mg-Al/kg-PHB and 750 mg-Fe/kg-PHB,
      respectively), no detectable amounts of Al and Fe were leached from films made of
      the recovered PHB under acidic conditions. The use of Fe-based coagulants is less
      recommended because the Fe impurity can cause an unwanted colorization problem in
      the final product.

PMID- 10933847
TI  - Functional expression of horseradish peroxidase in E. coli By directed evolution

PMID- 10933848
TI  - Elimination of matrix-based interferences to a fluorescent nitrite/nitrate assay
      by a simple filtration procedure.
AB  - Pathophysiological levels of oxygen radical metabolites have been studied as
      indicators of trauma caused by burn insult. The 2, 3-diaminonaphthalene assay is
      routinely used in the determination of nitrite/nitrate levels in biological
      fluids and cellular extracts as one indicator of nitric oxide activity. Several
      laboratories, including ours, have noted matrix-based interferences resulting in
      decreased assay sensitivity during nitrite/nitrate analysis. We evaluated
      filtration using Millipore Ultrafree-MC 10,000 NMWL filters for the ability to
      eliminate matrix-based interferences from human serum and tissue culture medium,
      thereby restoring assay sensitivity.

PMID- 10933849
TI  - Two-dimensional agarose gel electrophoresis as a tool to isolate genus- and
      species-specific repetitive DNA sequences.
AB  - Two-dimensional electrophoresis in agarose gels separates DNA-restriction
      fragments not only by molecular weight but also according to their AT-cluster
      content. The method produced genus-specific spot patterns of multicopy DNA
      fragments of grains as well as spot patterns of highly repetitive DNA fragments
      of ciliates, demonstrated for barley, spelt, and Tetrahymena. Further
      investigations in regard to their specificity by hybridization with three other
      grain species (wheat, oat, and rye) and three ciliate species (Tetrahymena
      thermophila, Tetrahymena pigmentosa, and Tetrahymena borealis) were performed.
      The DNA samples from spelt and Tetrahymena were demonstrated to be genus specific
      for Triticum and species specific for Tetrahymena pyriformis, respectively.

PMID- 10933851
TI  - Anchor polymerase chain reaction display: a high-throughput method to resolve,
      score, and isolate dimorphic genetic markers based on interspersed repetitive DNA
      elements.
AB  - Genes which confer a disease when mutated, or for which population variability
      contributes to a quantitative trait such as longevity or disease susceptibility,
      can be localized in the genetic map by use of an appropriately dense set of
      polymorphic DNA markers. Here we describe an anchor PCR method for high
      throughput genotyping, which can be used to amplify the DNA segments flanking an
      interspersed repetitive sequence such as a transposon, and to limit the number of
      product bands per reaction to facilitate marker resolution. We used this method
      to amplify and display DNA fragments flanking the Tc1 transposable elements from
      different strains of the nematode Caenorhabditis elegans, varying widely in
      insert number, and to analyze marker segregation in recombinant inbred lines
      generated from an interstrain cross. Since essentially all eukaryotic genomes
      contain abundant interspersed repeat families, many of which are dimorphic (for
      presence or absence of specific elements) among populations, this method can be
      used for rapid genotyping and fine-scale chromosomal mapping in many species,
      including those for which extensive mapping and sequencing data do not yet exist.

PMID- 10933850
TI  - Discrimination of primer 3'-nucleotide mismatch by taq DNA polymerase during
      polymerase chain reaction.
AB  - We investigated the effect of primer-template mismatch on the efficiency of
      polymerase chain reaction. For primers with T, C, or G as the 3' nucleotide,
      Thermus aquaticus (Taq) DNA polymerase was highly specific for template
      complementarity to this base, but was somewhat less constrained opposite the
      penultimate nucleotide. In contrast, primers with a 3'-terminal A were less
      efficiently amplified regardless of the corresponding nucleotide on the template
      strand. Thus, allele-specific PCR with Taq polymerase offers the greatest
      template discrimination (40- to 100-fold) against mismatch to a primer's 3'
      terminal T, G, or C, but not A. Nucleotides at the penultimate position are
      responsible for roughly one-fifth as much mismatch discrimination (8- to 20
      fold), and amplification efficiency is reduced when T and especially A occupy
      this primer position. We thus have defined conditions which allow robust
      discrimination for PCR-mediated analysis of single-nucleotide polymorphisms
      (SNPs), and for reduction in complexity of anchor-ligation PCR products.

PMID- 10933852
TI  - Noninvasive tracing of recombinant proteins with "fluorophenylalanine-fingers".
AB  - High-level residue-specific replacement of phenylalanine residues in recombinant
      human annexin V and azurin from Pseudomonas aeruginosa with o
      fluorophenylalanine, m-fluorophenylalanine, and p-fluorophenylalanine has been
      achieved using the selective pressure incorporation method. Incorporation was
      confirmed analytically and by UV spectroscopy while the secondary and tertiary
      structures of these protein mutants in solution remained unchanged upon the
      effected substitutions. Fluorinated phenylalanines alone and when integrated into
      proteins exhibit two characteristic and prominent shoulders ("fingers") in the UV
      spectrum in the range of 260-270 nm, which do not overlap with the contributions
      of tyrosine and tryptophan residues in the protein UV spectra. Thus, the presence
      of such "fluorophenylalanine fingers" ("FF fingers") opens a new spectral window
      to identify the labeled target protein among other nonlabeled cellular proteins
      in preparative work by simple UV spectroscopy. In the coming era of proteomics
      such a reliable, cheap, and easy reproducible methodology might have a great
      potential for speeding up the identification and characterization of target
      molecules in the total protein output from the genomes of a variety of organisms.

PMID- 10933854
TI  - In vivo determination of substrate specificity of hepatitis C virus NS3 protease:
      genetic assay for site-specific proteolysis.
AB  - Hepatitis C virus (HCV) NS3 protease is responsible for the processing of the
      viral polyprotein and is considered as a primary target for the development of
      anti-HCV therapy. We have developed a genetic method in yeast to screen for good
      substrate sequences of the NS3 protease. A library of fusion proteins was
      constructed with a transcription factor, GAL4, linked to the intracellular domain
      of an integral membrane protein, STE2, by a randomized protease substrate
      sequence. In yeast cells expressing NS3 protease, the substrate sequences in the
      fusion proteins were specifically recognized and cleaved. This cleavage resulted
      in the release of GAL4 from the cytoplasmic membrane and the subsequent
      activation of reporter genes by GAL4, which was detected by the growth of yeast
      cells on selective media. Based on the analysis of 69 isolated substrate
      sequences, a consensus sequence was deduced: (Glu/Asp)-X-Val-Val-(Leu/Pro)-Cys /
      (Ser/Ala), with the scissile bond being located between Cys and Ser or Ala and X
      not being determined. This is largely consistent with the previous results
      obtained by biochemical methods. An oligopeptide containing the deduced sequence
      was highly efficiently cleaved in vitro by the purified NS3 protease. These data
      demonstrated that the present genetic method could be used as an efficient tool
      for the in vivo determination of substrate specificity of proteases.

PMID- 10933853
TI  - Flow cytometry-based biosensor for detection of multivalent proteins.
AB  - Microsphere-based flow cytometric detection of cholera toxin (CT) through
      distance-dependent fluorescence resonant energy transfer (FRET) has been
      developed. Simultaneous double-fluorescence changes induced by multivalent
      interactions between CT and fluorophore (both fluorescence donor and acceptor)
      labeled ganglioside GM1 on a biomimetic membrane surface (supported bilayers of
      phospholipids) can be measured by a commercial flow cytometer, providing a
      convenient and sensitive detection method for CT. The flow cytometry-based
      biosensor is capable of detecting less than 10 pM CT within 30 min. The signal
      generation strategy coupled with flow cytometry also provides a convenient method
      for kinetic studies of multivalent interactions. The surface density and the
      ratio of donor/acceptor-labeled GM1 on the surfaces of phospholipid bilayers are
      optimized to achieve high sensitivity.

PMID- 10933855
TI  - Analysis of N-linked oligosaccharides released from glycoproteins separated by
      two-dimensional gel electrophoresis.
AB  - Protocols have been developed for the characterization of carbohydrate covalently
      attached (N-linked) to an asparagine residue in glycoproteins, after separation
      by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Mixtures of
      proteins (each at a level from 0.5 to 50 microg) were resolved in the first
      dimension according to their isoelectric points (pI), followed by separation in
      the orthogonal axis on the basis of their molecular weights. Glycans were
      released directly from excised gel spots after digestion with PNGase F, with or
      without prior treatment with trypsin. In a third method, glycoproteins were
      electroblotted onto poly(vinylidene difluoride) before glycans were released by
      PNGase F. For all these procedures profiles of the neutral and sialic acid
      containing oligosaccharide mixtures were obtained after derivatization with 3
      acetamido-6-aminoacridine, and analysis by matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry and/or high-performance
      liquid chromatography. Potential applications to proteomics are discussed.

PMID- 10933856
TI  - Effects of halothane, enflurane, and isoflurane on measurements of Ca(2+) by
      calcium electrode and aequorin luminescence.
AB  - We assessed the possible effects of the volatile halogenated anesthetics
      halothane, enflurane, and isoflurane on Ca(2+) electrode measurements and on the
      Ca(2+) sensitivity of the bioluminescent protein aequorin. In Ca(2+)-EGTA buffers
      of different pCa values (7. 870, 6.726, 6.033, 4.974, 4.038, and 2.995) and in
      serial Ca(2+) dilutions (10(-4), 10(-3), and 10(-2) M), halothane, enflurane, and
      isoflurane each caused a concentration-dependent and reversible increase in the
      absolute value of the negative electrode potential. Isoflurane and enflurane had
      larger effects than halothane. Neither of these anesthetics changed aequorin
      luminescence at any pCa tested in the range 2-8. There was no potentiation or
      inactivation of aequorin luminescence over a period of up to 2 h. These results
      suggest that (1) halothane, enflurane, and isoflurane interfere with Ca(2+)
      electrode measurements, most likely by changing the physicochemical properties of
      the membrane; (2) these anesthetics do not inactivate or otherwise modify the
      characteristics of the reaction of Ca(2+) with aequorin; and (3) these
      anesthetics do not change the apparent affinity of EGTA for Ca(2+).

PMID- 10933857
TI  - Determination of plasma free fatty acids by high-performance liquid
      chromatography with electrochemical detection.
AB  - Determination of free fatty acids (FFAs) in control serum and human plasma was
      carried out by high-performance liquid chromatography with electrochemical
      detection. Peak height for palmitic, palmitoleic, stearic, oleic, linoleic, and
      arachidonic acids at a detection potential of -415 mV vs a saturated calomel
      electrode showed a linear relation to acid amount in the range 50-1600 pmol. The
      present method for plasma free fatty acid determination required only 10 microL
      of plasma sample. The method is simple and the time for blood pretreatment is
      short. Change in plasma FFA with blood glucose level was monitored before and
      after meal ingestion by this method, using one male and one female subject. It
      was possible to rapidly reduce plasma FFA and increase blood glucose subsequent
      to the meal. The present method is thus shown to have potential for clinical
      application.

PMID- 10933858
TI  - An easy and accurate agarose gel assay for quantitation of bacterial plasmid copy
      numbers.
AB  - An assay for quantitation of plasmid copy numbers in bacterial cell cultures has
      been developed and validated. The method combines isolation of total bacterial
      DNA (including both plasmid and genomic DNA), running a series of twofold
      dilutions of total DNA in an agarose gel followed by ethidium bromide staining,
      and subsequent scanning of the gel picture negatives. We have developed a novel
      set of rules for integration of the scan data that allows us to achieve high
      assay precision, accuracy, and sensitivity. The assay validation results were as
      follows: intra- and interassay precision with %CV of 8.2-9.9 and 7.1-9.8%,
      respectively; ruggedness with %CV of 9.3-17.5%; spike recovery of 80-102%; and
      sensitivity of 1 plasmid copy per genome.

PMID- 10933859
TI  - Determination by electrospray mass spectrometry of the outersphere association
      constants of DNA/platinum complexes using 20-mer oligonucleotides and
      ([Pt(NH(3))(4)](2+), 2Cl(-)) or ([Pt(py)(4)](2+), 2Cl(-)).
AB  - The cytotoxic effects of cisplatin, cis-diamminedichloroplatinum(II), are
      generally ascribed to the formation of DNA adducts. Several in vitro as well as
      in vivo studies showed that cisplatin binds preferentially to guanines belonging
      to (G)(n) sequences (n > or = 2). After mono- or diaquation of cisplatin, giving
      the cationic complexes cis-[PtCl(NH(3))(2)(H(2)O)](+) and cis
      [Pt(NH(3))(2)(H(2)O)(2)](2+), DNA platination occurs in two steps: the cationic
      complex gives an outersphere association with DNA and the actual coordination
      then occurs by substitution of one aqua ligand by guanine-N7. For a better
      understanding of the (G)(n) selectivity of cisplatin giving the biologically
      active adducts, also necessary for the conception of new platinum drugs, the
      respective contribution of the outersphere association and actual guanine
      platination must be investigated. To check the role of outersphere association in
      the overall platination process, we used electrospray mass spectrometry (ESMS) to
      detect and quantify outersphere association between 20-mer oligonucleotides and
      platinum complexes. The 20-mer oligonucleotides were single- or double-stranded,
      with the same number of guanines either isolated or adjacent to each other. To
      deal only with outersphere association and check the influence of platinum
      ligands, the [Pt(NH(3))(4)](2+) and [Pt(py)(4)](2+) complexes were used. We
      characterized by ESMS all the different outersphere association species formed
      during titration of each oligonucleotide with the various platinum complexes and
      evaluated their affinity constants. The ESMS results demonstrate that the
      outersphere association depends on electrostatic interactions and on the ability
      of the platinum ligands to participate to hydrogen bonding, particularly within
      the duplex form.

PMID- 10933860
TI  - Fluorometric determination of mucin-type glycoproteins by the galactose oxidase
      peroxidase method.
AB  - We developed a convenient and specific method for the determination of mucin-type
      glycoproteins using galactose oxidase and horseradish peroxidase on the basis of
      the contents of galactosyl and N-acetylgalactosaminyl residues in glycoproteins.
      Galactose and galactosamine residues released from glycoproteins after hydrolysis
      were oxidized with galactose oxidase and subsequently the resultant hydrogen
      peroxide was determined by a combination of horseradish peroxidase and 3-(p
      hydroxyphenyl) propionic acid as a fluorogenic substrate. The contents of
      galactose/galactosamine residues in N- and O-glycans, as determined by the
      galactose oxidase-peroxidase method, were in good agreement with those described
      in the previous reports. We applied the present method to determine mucin-type
      glycoproteins secreted from rat gastric mucosa by stimulation with misoprostol, a
      prostaglandin E(1) analogue in vivo. Thus, the galactose oxidase-peroxidase
      method is useful for the determination of mucin-type glycoproteins in biological
      materials.

PMID- 10933861
TI  - A fluorometric method for measurement of oxygen radical-scavenging activity of
      water-soluble antioxidants.
AB  - The relative activities of the antioxidants Trolox, ascorbic acid, uric acid,
      quercetin, and rutin, and the activities of total antioxidants in serum samples
      were determined using a fluorometric assay based on the dye 6-carboxyfluoroscein
      (6C-Fl) as a fluorescent indicator; 2,2'-azobis-2-amidinopropane hydrochloride
      (AAPH) as a peroxyl radical generator; 6-hydroxy-2,5,7, 8-tetramethyl-1-chroman-2
      carboxylic acid (Trolox) as a calibrator; and phosphate buffer (pH 7.0) as a
      solvent. Incubation of 6C-Fl in 0. 075 M phosphate buffer, in the presence of
      AAPH at 37 degrees C, resulted in loss of its fluorescence signal at 520 nm with
      excitation at 495 nm. The antioxidants Trolox, ascorbic acid, and uric acid
      provided protection of the fluorescence of 6C-Fl, and the relative antioxidant
      activities, determined by the net protection area under curve technique, were
      found to be 1:0.4:1, respectively. Trolox and ascorbic acid were used to validate
      this assay. A linear correlation of the net protection value with the
      concentration of serum, Trolox, ascorbic acid, and uric acid was demonstrated.
      Quercetin and rutin were shown to have strong antioxidant activities, nearly 10
      times those of vitamin C. This assay is simple, reliable, and suitable for
      automation to handle many samples and requires few microliters of serum samples.

PMID- 10933862
TI  - Intrinsic bending in GGCC tracts as probed by fluorescence resonance energy
      transfer.
AB  - Double-stranded oligonucleotides containing the sequence 5'-GGCC-3' can be
      intrinsically bent, according to X-ray crystallography and gel electrophoresis
      mobility studies. We have performed fluorescence resonance energy transfer (FRET)
      experiments with dye-labeled oligonucleotides to further investigate the solution
      structure of this sequence. We find that 5'-GGCC-3'-containing oligonucleotides
      bring 5'-attached donor and acceptor dyes much closer together than a comparable
      "straight" sequence that contains 5'-GCGC-3'. The bend angle for the 5'-GGCC-3'
      sequence is estimated to be approximately 70 degrees, much larger than the
      crystallographically observed 23 degrees kink but in agreement with other FRET
      work. In contrast to gel electrophoresis studies, divalent metal ions do not
      promote increased kinking in 5'-GGCC-3' above background as judged by FRET. Thus,
      sequence-dependent structural effects in DNA may be a complicating feature of
      FRET experiments.

PMID- 10933863
TI  - Hybridization assay at a disposable electrochemical biosensor for the attomole
      detection of amplified human cytomegalovirus DNA.
AB  - A disposable electrochemical biosensor for the detection of DNA sequences related
      to the human cytomegalovirus (HCMV) is described. The sensor relies on the
      adsorption of an amplified human cytomegalovirus DNA strand onto the sensing
      surface of a screen-printed carbon electrode, and to its hybridization to a
      complementary single-stranded biotinylated DNA probe. The extent of hybrids
      formed was determined with streptavidin conjugated to horseradish peroxidase. The
      peroxidase label was indirectly quantified by measuring the amount of the
      chromophore and electroactive product 2,2'-diaminoazobenzene generated from the o
      phenylenediamine substrate. The intensity of differential pulse voltammetric peak
      currents resulting from the reduction of the enzyme-generated product was related
      to the number of target HCMV-amplified DNA molecules present in the sample, and
      the results were compared to those obtained with standard methods, i.e., agarose
      gel electrophoresis quantification and colorimetric hybridization assay in a
      microtiter plate. A detection limit of 0.6 amol/ml of HCMV-amplified DNA fragment
      was obtained with the electrochemical DNA biosensor. The electrochemical method
      was 23,000-fold more sensitive than the gel electrophoresis technique and 83-fold
      more sensitive than the colorimetric hybridization assay in a microtiter plate.

PMID- 10933864
TI  - Quantification of active caspase 3 in apoptotic cells.
AB  - We describe an enzyme-linked immunosorbent assay (ELISA) for quantifying relative
      amounts of active caspase 3 in apoptotic cells. Covalent modification of caspase
      3 active sites with a biotinylated inhibitor differentiates active from latent
      caspases. Capture on an ELISA plate with an antibody specific for caspase 3 makes
      the assay specific for caspase 3. Detection is with horseradish peroxidase (HRP)
      conjugated streptavidin that binds to the biotinylated inhibitor covalently bound
      to caspase 3. Using the assay we detected 6.6 ng active caspase 3 per 10(6)
      apoptotic staurosporine-treated Jurkat cells. Specificity of the assay for
      caspase 3 was demonstrated by lack of signal with purified caspases 2, 7, 8, and
      10 that were modified by a biotinylated inhibitor. Specificity was also
      demonstrated by lack of signal with apoptotic MCF-7 cells which do not express
      caspase 3. The ability to discriminate between active and latent caspase 3 was
      shown by Western blotting with HRP-streptavidin and anti-caspase 3. Although
      latent caspase 3 was captured it was not covalently modified with the
      biotinylated inhibitor. The basic principle of using a covalent inhibitor to
      identify active enzymes and an antibody to differentiate between enzymes with
      similar activities has potential for quantifying active members of many classes
      of enzymes.

PMID- 10933865
TI  - Synthesis and applications of stereospecifically (3)H-labeled arachidonic acids
      as mechanistic probes for lipoxygenase and cyclooxygenase catalysis.
AB  - Stereospecifically (3)H-labeled substrates are useful tools in studying the
      mechanism of hydrogen abstractions involved in the oxygenation of polyunsaturated
      fatty acids. Here, we describe modified methods for the synthesis of arachidonic
      acids labeled with a single chiral tritium on the methylene groups at carbons 10
      or 13. The appropriate starting material is a ketooctadecanoic acid which is
      prepared from an unsaturated C18 fatty acid precursor or by total synthesis. The
      (3)H label is introduced by NaB(3)H(4) reduction and the resulting tritiated
      hydroxy fatty acid then is tosylated, separated into the enantiomers by chiral
      phase HPLC, and subsequently transformed into stearic acids. A variety of
      stereospecifically labeled unsaturated fatty acids are obtained using literature
      methods of microbial transformation with the fungus Saprolegnia parasitica. Two
      applications are described: (i) In incubations of [10S-(3)H]- and [10R
      (3)H]arachidonic acids in human psoriatic scales we show that a 12R-lipoxygenase
      accounts not only for synthesis of the major product 12R-HETE, but it contributes
      also, through subsequent isomerization, to the minor amounts of 12S-HETE. (ii)
      The [10R-(3)H]- and [10S-(3)H]arachidonic acids were also used to demonstrate
      that prostaglandin ring formation by cyclooxygenases does not involve carbocation
      formation at C-10 of arachidonic acid as was hypothesized recently.

PMID- 10933866
TI  - High-performance cation-exchange chromatography and pulsed amperometric detection
      for the separation, detection, and quantitation of N-alkylated imino sugars in
      biological samples.
AB  - The use of imino sugars for the potential treatment of lysosomal glycolipid
      storage diseases and hepatitis virus infections requires accurate, quantitative
      measurement of these compounds in biological samples. We demonstrate here the
      versatility of cation-exchange chromatography and pulsed amperometric detection
      of a range of compounds that differ in both isometric structure and N-alkyl chain
      length. Although column retention appears dependent upon residual charge on the
      imine function, successful isocratic separation can be achieved by secondary
      hydrophobic interactions. A series of N-alkylated deoxynojirimycin compounds
      containing C(1-10) alkyl chains are readily separated and detected by pulsed
      amperometry after cation suppression. Using experimentally derived response
      factors for imino sugars and measurement of peak areas we have developed a
      reliable method for quantitatively determining concentrations in solution. A
      rapid protocol for the removal of protein and contaminants in biological samples
      is described. This has allowed the successful measurement of imino sugars in
      animal tissues and will be useful for understanding the factors involved in
      compound bioavailability and in the design of novel therapeutics.

PMID- 10933867
TI  - Reevaluation of the electrophoretic migration behavior of soluble globular
      proteins in the native and detergent-denatured states in polyacrylamide gels.
AB  - Although sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis is
      widely used for estimating molecular masses of proteins, considerable uncertainty
      still exists both about the structure of SDS-protein complexes and about their
      mechanism of electrophoretic migration. In this study, soluble globular proteins,
      with masses of 14-200 kDa, were heat-denatured in the presence of SDS and their
      relative total molecular volume and net charge were estimated from Ferguson plots
      of electrophoretic mobility vs acrylamide concentration. Native globular protein
      served as standards for overall molecular size and effective radii. Results
      revealed at least two independent electrophoretic migration mechanisms for the
      SDS-protein complexes: (i) for proteins in the 14-65 kDa range at <15%
      acrylamide, linear Ferguson plots suggested that they migrated ideally and that
      their effective radii could be estimated in this manner: (ii) concave plots at
      higher gel concentrations, and for complexes derived from larger proteins,
      indicated that migration in these cases could be described by reptation theory.
      Migration of the large proteins at lower gel concentrations and small proteins at
      higher gel concentrations was not well described by either theory, representing
      intermediate behavior not described by these mechanisms. These data support
      models in which all but the smallest SDS-protein complexes adopt a necklace-like
      structure in which spherical micelles are distributed along the unfolded
      polypeptide chain. Possible relations to recent alternative models of gel
      electrophoresis are also discussed.

PMID- 10933868
TI  - Changes in the time-resolved fluoroimmunoassay of plasma enterolactone.

PMID- 10933869
TI  - Use of 2-methylpropan-2-ol to inhibit proteolysis and other protein interactions
      in a tissue homogenate: an illustrative application to the extraction of
      cathepsins B and L from liver tissue.

PMID- 10933870
TI  - Polymerase chain reaction-single-strand conformation polymorphism based
      determination of two major genetic defects responsible for a phenotypic
      polymorphism of cytochrome P450 (CYP) 2C19 in the Japanese population.

PMID- 10933871
TI  - A micro-Bradford membrane protein assay.

PMID- 10933872
TI  - Isolation of single-stranded DNA using denaturing DNA chromatography.

PMID- 10933873
TI  - Polysaccharide labeling with N-methylisatoic anhydride: generation of ultraviolet
      chromophores and blue fluorophores.

PMID- 10933874
TI  - A biotin-conjugated substrate facilitating analysis of HIV-1 integrase activity
      on minigels.

PMID- 10933875
TI  - Induction of the heme oxygenase-1 gene by metalloporphyrins.
AB  - Induction of expression of heme oxygenase-1 (HO-1) has been studied in primary
      cultures of chick embryo liver cells and in the LMH line of avian hepatoma cells.
      Cells were transiently transfected with selected constructs containing portions
      of the 5'-untranslated (promoter) region of the HO-1 gene linked to luciferase as
      reporter gene. LMH cells that had been stably transfected with selected wild type
      or mutant constructs were also studied. Metalloporphyrins, especially Fe
      protoporphyrin (heme) and Co protoporphyrin strongly induced luciferase
      expression in both types of transfected cells. Low concentrations of Zn
      mesoporphyrin, an inhibitor of HO activity, exerted a synergistic effect on heme
      , but not Co protoporphyrin-dependent induction. The antioxidant and &bond;SH
      donor N-acetyl cysteine had little effect on the metalloporphyrin-dependent
      inductions of HO-1, in contrast to its marked inhibitory effect on the sodium
      arsenite-dependent induction of the HO-1 gene. Deletional analysis showed that
      the key element(s) required for the metalloporphyrin-dependent induction of HO-1
      is located between -3.6 and -5.6 kb upstream of the transcription starting point.
      Data from electrophoretic mobility shift and site-directed mutagenesis
      experiments excluded a role for consensus AP-1 binding elements at -1576, -3647,
      or -4578 in the inductions produced by heme or Co protoporphyrin.

PMID- 10933876
TI  - A nuclear matrix-associated factor, SAF-B, interacts with specific isoforms of
      AUF1/hnRNP D.
AB  - One class of heterogeneous nuclear ribonucleoproteins (hnRNPs), AUF1/hnRNP D,
      consists of four isoform proteins (p45, p42, p40, and p37) which are generated by
      alternative splicing. The present study was therefore undertaken to clarify any
      isoform-specific differences in terms of their functions and nucleocytoplasmic
      localization. All isoforms primarily localized in the nucleus. However,
      heterokaryon analysis and a study using RNA polymerase II inhibitor revealed that
      p40/p37 exhibited a continuous shuttling between the nucleus and cytoplasm.
      Constant nuclear retention activity was mapped to the p45/p42-specific sequence
      at the C-terminal region, which is retained by alternative splicing. Using this
      domain as a probe, we performed a yeast two-hybrid screening and we found that
      scaffold attachment factor B (SAF-B), a nuclear matrix-associated protein,
      exhibits protein-protein interaction to this region. Colocalization of p45/p42
      and SAF-B was observed as a speckle in the nucleus. Interestingly, p45/p42
      isoforms appeared to act as a negative regulator in gene expression by forming a
      complex with SAF-B. Thus, the present study revealed that the isoform-specific
      functions of AUF1/hnRNP D are defined by intracellular shuttling capacity.

PMID- 10933877
TI  - Ebselen lowers plasma interleukin-6 levels and glial heme oxygenase-1 expression
      after focal photothrombotic brain ischemia.
AB  - Heme oxygenase-1, an inducible heat shock protein, is upregulated by oxidative
      stress, and its expression is modulated by proinflammatory cytokines such as IL-1
      and IL-6. In the present study, we investigated the effects of postlesional,
      orally applied ebselen, a neuroprotective antioxidant, on serum levels of IL-6
      and cerebral heme oxygenase-1 expression following focal ischemia induced by
      photothrombosis. Ebselen (50 mg/kg body weight) was given 30 min postlesion to
      male Wistar rats. Animals were divided into four groups: sham-operated vehicle
      control (n = 9), sham-operated ebselen control (n = 8), lesioned vehicle control
      (n = 14), and lesioned ebselen-treated (n = 17). Ebselen treatment resulted in a
      significant lowering of IL-6 plasma levels (26 +/- 5 pg/ml) as compared with that
      seen in lesioned vehicle controls (48 +/- 9 pg/ml) at 24 h postlesion. In sham
      operated rats IL-6 was not detectable. Heme oxygenase-1-positive glial cells were
      quantitated within topographically determined perilesional brain regions. Within
      the 0.5-mm-wide rim region directly associated with the lesion core, no
      differences in the amount of heme oxygenase-1-positive glial cells were found.
      However, in the more remote ipsilateral perilesional cortex, significantly fewer
      heme oxygenase-1-positive glial cells were present within the supragranular
      cortical layers of lesioned ebselen-treated rats compared to lesioned vehicle
      controls (P < 0.001). In sham-operated rats, no glial heme oxygenase-1 induction
      occurred. The results indicate that postlesional ebselen treatment lowered plasma
      IL-6 levels subsequent to a photothrombotic lesion concomitant with a lowering of
      the heme oxygenase-1 response in glial cells.

PMID- 10933878
TI  - Stearoyl-CoA desaturase 1 coding sequences and antisense RNA affect lipid
      secretion in transfected chicken LMH hepatoma cells.
AB  - Hepatic stearoyl CoA desaturase (SCD) activity in chickens from a fat line is
      higher than that of chickens from a lean line and correlates with plasma
      triacylglycerol concentrations. Furthermore, in these lines, the hepatic SCD1
      mRNA level is positively correlated with the adipose tissue weight. To analyze
      the contribution of the SCD1 gene in the regulation of adiposity in the early
      stages of triacylglycerol secretion, SCD1 coding sequence and antisense RNA
      expression vectors were transfected in LMH cells. After selection, these cells
      were analyzed with regard to SCD1 expression and lipid secretion. The amounts of
      secreted triacylglycerols and phospholipids were shown to be higher in LMH cells
      transfected with the SCD1 gene, but reduced in those transfected with the SCD1
      antisense sequences when compared to cells transfected with the vector alone
      (without SCD1 sequences). These results provide direct evidence that the
      expression of the SCD1 gene plays a major role in the triacylglycerol and
      phospholipid secretion process.

PMID- 10933879
TI  - Promethazine oxidation by redox mediation in peroxidase reactions.
AB  - The effect of promethazine on peroxidase-catalyzed oxidation of 3,3', 5,5'
      tetramethylbenzidine was investigated at pH 5.4. Promethazine dose dependently
      introduced a lag in the appearance of tetramethylbenzidine charge-transfer
      complex monitored at 652 nm. Increasing concentrations of tetramethylbenzidine
      however decreased the lag period proportional to the tetramethylbenzidine
      concentration. Addition of promethazine to preformed charge transfer complex
      caused rapid bleaching of the blue-colored complex. Titration of promethazine
      with the yellow-colored diimine gave rise to the blue charge-transfer complex and
      the complete reduction of the species to the colorless parent amine compound. The
      available evidence suggests that promethazine is oxidized via redox mediation by
      tetramethylbenzidine peroxidase-oxidized products.

PMID- 10933880
TI  - Purification and properties of multiple isoforms of a novel thiol
      methyltransferase involved in the production of volatile sulfur compounds from
      Brassica oleracea.
AB  - Five functional isoforms of a novel plant thiol methyltransferase from the leaves
      of cabbage (Brassica oleracea L.) were purified to electrophoretic homogeneity.
      Pooled, partly purified preparations of the enzyme were previously shown to
      methylate thiol compounds released upon the hydrolysis of glucosinolates. The
      enzyme could also accept halide ions as substrates. The estimated molecular
      masses of the purified isoforms ranged between 26 and 31 kDa. The three most
      abundant isoforms of the enzyme could all catalyze the S-adenosyl-l-methionine
      dependent methylation of thiocyanate, a number of organic thiols and iodide.
      However, the kinetic properties of these forms toward various substrates differed
      widely. None of the isoforms examined methylated the O- and N-equivalents of the
      thiol substrates. The three isoforms also had distinct pH optima, covering the
      range from 5 to 9. Their kinetic analysis indicated that they shared a sequential
      substrate binding mechanism and an Ordered Bi Bi mechanism for substrate binding
      and product release. Partial internal amino acid sequence from one isoform showed
      high similarity to an Arabidopsis EST of unknown function, and to a recently
      cloned methyl chloride transferase from Batis maritima. The differences in the pH
      optima and kinetic properties of the isoforms suggest that each may methylate a
      specific substrate or a narrow group of substrates under cellular conditions.

PMID- 10933881
TI  - Copper-mediated toxicity of 2,4,5-trichlorophenol: biphasic effect of the
      copper(I)-specific chelator neocuproine.
AB  - The lipophilic copper(I)-specific chelator neocuproine has been frequently used
      as an inhibitor of copper-mediated damage in biological systems. In this
      communication we report that the copper-mediated toxicity of 2,4,5
      trichlorophenol is markedly potentiated by neocuproine at levels which are near
      stoichiometric with respect to the copper concentration but is inhibited at
      higher concentrations. However, no potentiation was observed when neocuproine was
      substituted by bathocuproinedisulfonic acid, a negative charged ligand with
      essentially the same copper-binding characteristics as neocuproine. We found that
      the potentiation by neocuproine was due to the formation of a lipophilic copper
      complex, while the inhibition by bathocuproinedisulfonic acid was due to the
      formation of a hydrophilic one. Caution in the use of neocuproine to study copper
      mediated toxicity is advised.

PMID- 10933882
TI  - Kinetic and functional characterization of 1,4-dideoxy-1, 4-imino-d-arabinitol: a
      potent inhibitor of glycogen phosphorylase with anti-hyperglyceamic effect in
      ob/ob mice.
AB  - The effects of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) were investigated on
      preparations of glycogen phosphorylase (GP) and in C57BL6J (ob/ob) mice by (13)C
      NMR in vivo. Independent of the phosphorylation state or the mammalian species or
      tissue from which GP was derived, DAB inhibited GP with K(i)-values of
      approximately 400 nM. The mode of inhibition was uncompetitive or noncompetitive,
      with respect to glycogen and P(i), respectively. The effects of glucose and
      caffeine on the inhibitory effect of DAB were investigated. Taken together, these
      data suggest that DAB defines a novel mechanism of action. Intraperitoneal
      treatment with DAB (a total of 105 mg/kg in seven doses) for 210 min inhibited
      glucagon-stimulated glycogenolysis in obese and lean mice. Thus, liver glycogen
      levels were 361 +/- 19 and 228 +/- 19 micromol glucosyl units/g with DAB plus
      glucagon in lean and obese mice, respectively, compared to 115 +/- 24 and 37 +/-
      8 micromol glucosyl units/g liver with glucagon only. Moreover, with glucagon
      only end-point blood glucose levels were at 29 +/- 2 and 17.5 +/- 2 mM in obese
      and lean mice, respectively, compared to 17.5 +/- 1 and 12 +/- 1 mM with glucagon
      plus DAB. In conclusion, DAB is a novel and potent inhibitor of GP with an
      apparently distinct mechanism of action. Further, DAB inhibited the hepatic
      glycogen breakdown in vivo and displayed an accompanying anti-hyperglycemic
      effect, which was most pronounced in obese mice. The data suggest that inhibition
      of GP may offer a therapeutic principle in Type 2 diabetes.

PMID- 10933883
TI  - ATP's impact on the conformation and holoenzyme formation in relation to the
      regulation of brain glutamate decarboxylase.
AB  - To investigate ATP as a potential factor in the regulation of brain glutamate
      decarboxylase (GAD), the impact of ATP on the enzyme conformation and holoenzyme
      formation was investigated. ATP at 100 microM quenches fluorescence emission
      intensity of the holoenzyme of GAD (holoGAD) by 18% after a correction for the
      inner filter effect and enhances fluorescence steady-state polarization from
      0.158 to 0. 183 when excited at 280 or 295 nm. These findings suggest that ATP
      moderately changes the microenvironment of one or more tryptophan or tyrosine
      residues in holoGAD and alters these residues from a more mobile state to a less
      mobile one. A moderate ATP-induced conformational change in holoGAD is also
      supported by the observations that ATP increases the thermal denaturation
      temperature of holoGAD by 2 degrees C, as derived from temperature-dependent
      fluorescence spectra, and decreases the alpha-helical content of holoGAD by 8
      10%, as determined by circular dichroism. Moreover, ATP does not affect the keto
      enol tautomerization of holoGAD and has little or no direct effect on its
      activity, implying that the ATP interacting domain in holoGAD is not at the
      active site. Kinetics studies, as demonstrated by stopped-flow fluorescence and
      UV/visible spectroscopy, demonstrate that formation of holoGAD involves two
      steps: a fast reaction forming an apoGAD-cofactor intermediate complex, followed
      by a slow reaction involving the conformational change in the intermediate
      complex. ATP reduces the rate constant of the fast step to one-third and
      decreases the rate of the slow step and the intermediate complex formation
      constant to 60% of their original values. The present data suggest that ATP may
      regulate the interconversion between apoGAD and holoGAD by interacting with
      apoGAD rather than holoGAD. By slowing down the rate of intermediate complex
      formation, ATP reduces the amount of holoGAD formed.

PMID- 10933884
TI  - Linoleic acid diols are novel substrates for human UDP-glucuronosyltransferases.
AB  - Linoleic acid diol glucuronides have been isolated previously from urine of
      patients suffering from generalized peroxisomal disorders. Glucuronidation of
      linoleic acid and linoleic acid diols by human liver microsomes was studied to
      investigate the role of glucuronide conjugation in the metabolism of linoleic
      acid diols. Glucuronide products were isolated and analyzed by TLC and HPLC-MS.
      HPLC-MS showed ions with (m/z) corresponding to singly glucuronidated linoleic
      acid diols while TLC revealed that the glucuronidation was at a hydroxyl
      position. Kinetic analysis gave apparent K(m) values in the range of 50-200
      microM and V(max) rates from 5 to 12 nmol/mg x min. These rates are substantially
      higher than activities seen for most endogenous hydroxylated substrates. Assays
      using each of the four individually purified linoleic acid diol enantiomers
      suggest that glucuronidation occurs at only one of the two hydroxyl groups of
      each enantiomer. These results show for the first time that hydroxylated fatty
      acids are actively glucuronidated by human liver microsomes and suggest that
      glucuronidation may play a significant role in the biotransformation of linoleic
      acid diols in humans.

PMID- 10933885
TI  - The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused
      not only by the low-expression but also by low affinity of CYP2D6.
AB  - CYP2D6 exhibits genetic polymorphism with interindividual differences in
      metabolic activity. We have found a significant influence on the pharmacokinetics
      of venlafaxine by the CYP2D6*10 allele in a Japanese population. CYP2D6.10, which
      is translated from CYP2D6*10, has two amino acid substitutions: Pro34 --> Ser and
      Ser486 --> Thr. In this study, CYP2D6.10 was expressed in Saccharomyces
      cerevisiae and its catalytic activity for CYP2D6 substrates was investigated. The
      CYP2D6*10B- and *10C-associated cDNA were isolated from human lymphocyte
      genotyped as CYP2D6*10. In addition, three forms of CYP2D6, Pro34/Thr486 (PT),
      Ser34/Ser486 (SS), and Pro34/Ser486 (wild type, CYP2D6.1), were constructed by
      PCR-site mutagenesis to clarify the effects of the two amino-acid substitutions.
      The expression of CYP2D6 protein was confirmed by immunoblotting using CYP2D
      antibody. The absorbance at 450 nm was measured by CO-reduced difference spectra
      from five all microsome preparations. The CYP2D6 forms with Pro34 --> Ser amino
      acid substitution were at a lower expression than CYP2D6.1 from the findings of
      immunoblotting and spectral analysis. The apparent K(m) values of CYP2D6.1,
      CYP2D6.10A, and CYP2D6.10C were 1.7, 8.5, and 49.7 microM, respectively, for
      bufuralol 1'-hydroxylation, and 9.0, 51.9, and 117.4 microM, respectively, for
      venlafaxine O-demethylation, respectively. The V(max) values were not
      significantly different among the three variants. These findings suggest that the
      decreased in vivo clearance by CYP2D6*10 was caused not only by low expression of
      but also the increased K(m) value of CYP2D6.

PMID- 10933886
TI  - Activation of thiol-dependent antioxidant activity of human serum albumin by
      alkaline pH is due to the B-like conformational change.
AB  - Antioxidant activity of human serum albumin (HSA) increased steeply as the
      reaction mixture was shifted from neutral to alkaline pH. The antioxidant
      activity was also remarkably increased by Ca(2+) or a cationic detergent
      (cetyltrimethylammonium chloride). Carboxyl group modification of HSA resulted in
      about 40-fold increase of the antioxidant activity. The chemical modification
      study indicated that in addition to functional cysteine(s), cationic amino acid
      residues such as histidine, arginine and lysine appeared to involve in the
      antioxidant reaction. HSA also exhibited alkaline-pH dependent peroxidase
      activity to remove fatty acid hydroperoxide. At neutral pH, only two thiols of
      Cys-289 and free Cys-34 of HSA were modified by a thiol-specific modification
      reagent, 5-((((2-iodoacetyl)amino)ethy)amino)naphthalene-1-sulfonic acid (I14),
      regardless of the presence or absence of dithiothreitol (DTT), and the resultant
      antioxidant activity was not decreased, suggesting that Cys-289 and Cys-34 did
      not participate in the antioxidant reaction. At alkaline pH, I14 modified several
      additional HSA thiols in the presence, but did not in the absence of DTT. The
      antioxidant activity of the modified HSA was remarkably decreased to as much as
      30% of the antioxidant activity given by the unmodified HSA in the absence of
      DTT. The HPLC pattern for tryptic peptides containing modified cysteine(s)
      derived from the I14-treated c-HSA (carboxyl group-modified HSA) at pH 7.0 with
      DTT was very similar to that of the I14-modified HSA at pH 8.0 with DTT. Taken
      together, these results suggest that activation of thiol-dependent antioxidant
      activity of HSA at alkaline pH is due to the conformational change favorable for
      the functional cysteine(s)-mediated catalysis.

PMID- 10933887
TI  - Intracellular thiol depletion causes mitochondrial permeability transition in
      ebselen-induced apoptosis.
AB  - Ebselen, a selenoorganic compound, has recently been shown to display a novel
      property of inducing apoptosis through rapid depletion of intracellular thiols in
      human hepatoma cells, HepG(2). The present study was thus designed to explore the
      mechanism of how ebselen triggers apoptosis upon depletion of intracellular
      thiols. The results demonstrated that ebselen treatment triggered mitochondrial
      permeability transition rather rapidly as revealed by redistribution of calcein
      green fluorescence from cytosol into mitochondria. Ebselen treatment also caused
      a dose- and time-dependent loss of mitochondrial membrane potential (MMP) and
      release of cytochrome c. Pretreatment with N-acetylcysteine, a precursor of
      intracellular reduced glutathione (GSH) synthesis, significantly attenuated the
      ebselen-induced MMP disruption and subsequently inhibited the apoptosis. In
      contrast, pretreatment with buthionine sulfoximine, a specific inhibitor of
      intracellular GSH synthesis, significantly augmented the ebselen-induced MMP
      alteration, and enhanced the apoptosis. Although ebselen treatment significantly
      increased the intracellular superoxide radical and calcium concentrations,
      superoxide dismutase, and BAPTA (a calcium chelator), however, failed to prevent
      ebselen-induced MMP loss and apoptosis. Neither caspase-9 nor caspase-3
      activation was detected in ebselen-treated cells. Z-VAD-FMK, a general caspase
      inhibitor, also had no effect on ebselen-induced MMP decrease and apoptosis. The
      overall findings thus suggest that mitochondrial permeability transition resulted
      from intracellular thiol depletion is a critical event in ebselen-induced
      apoptosis.

PMID- 10933888
TI  - Essential role of trehalose in the synthesis and subsequent metabolism of
      corynomycolic acid in Corynebacterium matruchotii.
AB  - A previous paper indicated that corynomycolates synthesized by the fluffy layer
      fraction prepared from Corynebacterium matruchotii cells appeared exclusively as
      alpha-trehalose 6-monocorynomycolate (TMM) (T. Shimakata, K. Tsubokura, T.
      Kusaka, and K. Shizukuishi, 1985, Arch. Biochem. Biophys. 238, 497-508). In the
      present communication, the role of trehalose in the synthesis and subsequent
      metabolism of corynomycolic acids was reexamined. Consequently the following
      facts were clarified: (i) trehalose 6-phosphate (T-6-P), but not trehalose,
      stimulated corynomycolate synthesis from palmitate in the presence of ATP; the
      immediate product was TMM, which showed a rapid turnover. Since the turnover was
      blocked by addition of alpha-trehalose, only TMM accumulated among corynomycolate
      containing substances. These results strongly suggested that T-6-P is an
      essential component as the acceptor in corynomycolate-synthetic system; (ii) TMM
      was the precursor not only to alpha-trehalose 6,6'-dicorynomycolate (TDM) and
      free corynomycolic acids but also to cell wall corynomycolate; (iii) addition of
      alpha-trehalose blocked the transfer of the corynomycolate moiety from TMM to
      cell wall corynomycolate, TDM, and free corynomycolic acids to a similar extent.
      These results clearly indicate that trehalose plays an essential role in the
      metabolism of corynomycolate after Claisen condensation and subsequent reduction
      in C. matruchotii.

PMID- 10933889
TI  - Role of Ser(289) in RARgamma and its homologous amino acid residue of RARalpha
      and RARbeta in the binding of retinoic acid.
AB  - The biological actions of retinoic acid (RA) are mediated by retinoic acid
      receptors (RARalpha, -beta, and -gamma) and retinoid X receptors (RXRalpha, 
      beta, and -gamma). Although the ligand-binding domains of RARs and RXRs have been
      suggested to share the same novel folding pattern, the ligand-binding pockets of
      each of the retinoid receptors must have unique structural features since it has
      been possible to develop RAR subtype-selective and RXR-selective retinoids. We
      have previously demonstrated the importance for RA binding and RA-dependent
      transactivation of Arg(276) in RARalpha and Arg(278) in RARgamma; however, in
      RARbeta Arg(269) functions in conjunction with Lys(220). Here we have examined
      the role of the hydroxyl group of RARgamma Ser(289) and its homologous amino acid
      residues in RARalpha (Ser(287)) and RARbeta (Ser(280)) alone and in conjunction
      with their respective RARgamma Arg(278) homologs for RA binding and RA-dependent
      transactivation activity. The hydroxyl group of this Ser in all three RARs was
      found by itself not to be important for RA binding and RA-dependent
      transactivation activity. However, in RARalpha and RARgamma this Ser appears to
      play a small role in conjunction with Arg(276) and Arg(278), respectively, for
      these activities. Alternatively, strong synergism was observed in RARbeta between
      Ser(280) and Arg(269) for RA-binding and RA-dependent transactivation activity.
      This provides further evidence that the mechanism of interaction between the
      carboxylate group of retinoids and the amino acid residues in the ligand binding
      pocket of RARbeta is different from that of RARalpha and RARgamma.

PMID- 10933890
TI  - Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement
      of Glut1-mediated glucose transport.
AB  - In cells expressing only the Glut1 isoform of glucose transporters, we have shown
      that glucose transport is markedly stimulated in response to hypoxia or
      inhibition of oxidative phosphorylation, conditions that would be expected to
      cause a stimulation of AMP-activated protein kinase (AMPK) activity. In the
      present study we tested the hypothesis that the stimulation of AMPK activity
      might be accompanied by an enhancement of Glut1-mediated glucose transport.
      Exposure of Clone 9 cells, 3T3-L1 preadipocytes, and C(2)C(12) myoblasts (cells
      that express only the Glut1 isoform) to 5-aminoimidazole-4
      carboxamideribonucleoside (AICAR), an adenosine analog that stimulates AMPK
      activity, resulted in a marked increase in the rate of glucose transport (ranging
      from four- to sixfold) that was accompanied by activation of AMPK. This
      stimulation of AMPK activity was associated with an increase in the
      phosphorylation of threonine 172 on the activation loop of its alpha subunit,
      with the predominant change being in the alpha-2 isoform. Exposure of Clone 9
      cells to 5-iodotubercidin, an inhibitor of adenosine kinase, abolished the
      accumulation of AICAR-5'-monophosphate (ZMP), stimulation of AMPK, and the
      enhancement of glucose transport in response to AICAR. There was no significant
      increase in the content of Glut1 in plasma membranes of Clone 9 cells exposed to
      AICAR. We conclude that stimulation of AMPK activity is associated with
      enhancement of Glut1-mediated glucose transport, and that the glucose transport
      response is mediated by activation of Glut1 transporters preexisting in the
      plasma membrane.

PMID- 10933891
TI  - Peroxisome proliferator-activated receptor alpha (PPARalpha) activators,
      bezafibrate and Wy-14,643, increase uncoupling protein-3 mRNA levels without
      modifying the mitochondrial membrane potential in primary culture of rat
      preadipocytes.
AB  - Uncoupling proteins (UCPs) are inner mitochondrial membrane transporters which
      act as pores for H(+) ions, dissipating the electrochemical gradient that
      develops during mitochondrial respiration at the expense of ATP synthesis. We
      have studied the effects of two fibrates, bezafibrate and Wy-14,643, on UCP-3 and
      UCP-2 mRNA levels in primary monolayer cultures of rat adipocytes and
      undifferentiated preadipocytes. Treatment with both PPARalpha activators for 24 h
      up-regulated UCP-3 mRNA levels. Thus, bezafibrate treatment resulted in an 8-fold
      induction in UCP-3 mRNA levels in preadipocytes compared with the 3.5-fold
      induction observed in adipocytes. Differences in the induction of UCP-3 between
      these cells correlated well with the higher expression of PPARalpha and RXRalpha
      mRNA values in preadipocytes compared to adipocytes. Wy-14,643 caused similar
      effects on UCP-3 mRNA expression. In contrast to UCP-3, UCP-2 mRNA levels were
      only slightly modified by bezafibrate in adipocytes. The induction in UCP-3
      expression was not accompanied by changes in the mitochondrial membrane potential
      of rat primary preadipocytes after bezafibrate or Wy-14,643 treatment. Since it
      has been proposed that UCP-3 could be involved in the regulation of the use of
      fatty acids as fuel substrates, the UCP-3 induction achieved after bezafibrate
      and Wy-14, 643 treatment may indicate a higher oxidation of fatty acids, limiting
      their availability to be stored as triglycerides. This change may result in a
      reduced rate of conversion of preadipocytes to adipocytes, which directly affects
      fat depots.

PMID- 10933892
TI  - Proteolytic degradation of tyrosine nitrated proteins.
AB  - Tyrosine nitration is a covalent posttranslational protein modification that has
      been detected under several pathological conditions. This study reports that
      nitrated proteins are degraded by chymotrypsin and that protein nitration
      enhances susceptibility to degradation by the proteasome. Chymotrypsin cleaved
      the peptide bond between nitrated-tyrosine 108 and serine 109 in bovine Cu,Zn
      superoxide dismutase. However, the rate of chymotryptic cleavage of nitrated
      peptides was considerably slower than control. In contrast, nitrated bovine Cu,Zn
      superoxide dismutase was degraded at a rate 1. 8-fold faster than that of control
      by a gradient-purified 20S/26S proteasome fraction from bovine retina. Exposure
      of PC12 cells to a nitrating agent resulted in the nitration of tyrosine
      hydroxylase and a 58 +/- 12.5% decline in the steady-state levels of the protein
      4 h after nitration. The steady-state levels of tyrosine hydroxylase were
      restored by selective inhibition of the proteasome activity with lactacystin.
      These data indicate that nitration of tyrosine residue(s) in proteins is
      sufficient to induce an accelerated degradation of the modified proteins by the
      proteasome and that the proteasome may be critical for the removal of nitrated
      proteins in vivo.

PMID- 10933893
TI  - Short-term hypothermia activates hepatic mitochondrial sn-glycerol-3-phosphate
      dehydrogenase and thermogenic systems.
AB  - The contribution of the sn-glycerol-3-phosphate (G-3-P) shuttle in the control of
      energy metabolism is well established. It is also known that its activity may be
      modulated by hormones involved in thermogenesis, such as thyroid hormones or
      dehydroepiandrosterone and its metabolites, that act by inducing de novo
      synthesis of mitochondrial G-3-P dehydrogenase (mGPDH). However, little is known
      as to the factors that may influence the activity without enzyme induction. In
      the present study we investigated the possible role of the G-3-P shuttle in the
      thermogenic response to different hypothermic stresses. It was found that a
      decrease of body temperature causes the liver rapidly to enhance mGPDH activity
      and G-3-P-dependent respiration. The enhancement, which does not result from de
      novo synthesis of enzymes, has the potential of increasing heat production both
      by decreased ATP synthesis during the oxidation of G-3-P and by activation of the
      glycolytic pathway.

PMID- 10933894
TI  - 2,4-Dienoyl-CoA reductase from Escherichia coli is a novel iron-sulfur
      flavoprotein that functions in fatty acid beta-oxidation.
AB  - 2,4-Dienoyl-CoA reductase is an enzyme that is required for the beta-oxidation of
      unsaturated fatty acids with even-numbered double bonds. The 2,4-dienoyl-CoA
      reductase from Escherichia coli was studied to explore the catalytic and
      structural properties that distinguish this enzyme from the corresponding
      eukaryotic reductases. The E. coli reductase was found to contain 1 mol of flavin
      mononucleotide and 4 mol each of acid-labile iron and sulfur in addition to 1 mol
      of flavin adenine dinucleotide per mole of protein. Redox titrations revealed a
      requirement for 5 mol of electrons to completely reduce 1 mol of enzyme and
      provided evidence for the formation of a red semiquinone intermediate. The
      reductase caused a significant polarization of the substrate carbonyl group as
      indicated by an enzyme-induced red shift of 38 nm in the spectrum of 5-phenyl-2,4
      pentadienoyl-CoA. However, suspected cis --> trans isomerase and
      Delta(3),Delta(2)-enoyl-CoA isomerase activities were not detected in this
      enzyme. It is concluded that the 2, 4-dienoyl-CoA reductases from E. coli and
      eukaryotic organisms are structurally and mechanistically unrelated enzymes that
      catalyze the same type of reaction with similar efficiencies.

PMID- 10933895
TI  - Membrane binding of MARCKS-related protein studied by tryptophan fluorescence
      spectroscopy.
AB  - MARCKS-related protein (MRP) is a peripheral membrane protein whose binding to
      membranes is mediated by the N-terminal myristoyl moiety and a central, highly
      basic effector domain. MRP mediates cross-talk between protein kinase C and
      calmodulin and is thought to link the actin cytoskeleton to the plasma membrane.
      Since MRP contains no tryptophan residues, we mutated a phenylalanine in the
      effector domain to tryptophan (MRP F93W) and used fluorescence spectroscopy to
      monitor binding of the protein to phospholipid vesicles. We report in detail the
      evaluation procedure necessary to extract quantitative information from the raw
      data. The spectra of MRP F93W obtained in the presence of increasing amounts of
      lipid crossed at an isosbestic point, indicating a simple transition between two
      states: free and membrane-bound protein. The change in fluorescence toward values
      typical of a more hydrophobic environment was used to quantify membrane binding.
      The partition coefficient agreed well with values obtained previously by other
      methods. To study the interaction of the N-terminus of MRP with membranes, a
      tryptophan residue was also introduced at position 4 (MRP S4W). Our data suggest
      that only the myristoylated N-terminus interacted with liposomes. These results
      demonstrate the versatility of site-directed incorporation of tryptophan residues
      to study protein-membrane interactions.

PMID- 10933896
TI  - Effects of multisensory environmental stimulation on contextual conditioning in
      the developing rat.
AB  - The effect of increased exposure to multisensory stimulation during development
      on conditioned freezing to contextual cues in preweanling Sprague-Dawley rats was
      examined. Rats given increased environmental stimulation exhibited long-term
      contextual conditioning at a younger age than rats that did not receive such
      stimulation when there was either low or moderate levels of conditioning
      (Experiments 1 and 2). These differences in contextual conditioning were not a
      result of the stimulated rats reacting differently to shock (Experiment 4) or
      merely freezing more than the nonstimulated rats in all situations (Experiment
      3). The role of the glucocorticoid system in the enhanced contextual learning of
      stimulated preweanling rats and the advantages of the contextual conditioning
      procedure for studying the effects of environmental stimulation are discussed.

PMID- 10933897
TI  - Electrolytic lesions of the pedunculopontine nucleus disrupt concurrent learned
      aversion induced by NaCl.
AB  - Bilateral electrolytic lesions in the pedunculopontine nucleus (PPN) impair
      acquisition of short-term, or concurrent, Taste Aversion Learning (TAL) in rats.
      This type of TAL is characterized by the daily presentation of two different
      flavor stimuli at the same time, one associated with simultaneous intragastric
      administration of an aversive product (hypertonic NaCl) and the other with
      physiological saline. Sham-lesioned control animals learn this taste
      discrimination task, but both lesioned animals and control animals learn a long
      term, or delayed, TAL task in which each gustatory stimulus is presented
      individually every other day and the intragastric products, LiCl (0.15 M) and
      physiological saline, are administered after a 15-min delay. These results are
      analyzed in the context of the cerebellar circuits involved in learning and in
      relation to the two TAL modalities described above.

PMID- 10933898
TI  - Long-lasting and context-specific freezing preference is acquired after spaced
      repeated presentations of a danger stimulus in the crab Chasmagnathus.
AB  - A visual danger stimulus elicits an escape response in the crab Chasmagnathus
      that declines after repeated presentations. Previous results report that such
      waning may be retained as context-signal memory (CSM) or signal memory (SM): CSM
      is long lasting, associative, and produced by spaced training, while SM is an
      intermediate memory, nonassociative, and produced by massed training. The
      performances of both spaced and massed trained crabs are here examined, using
      video analysis to determine topographic changes in the behavioral response during
      and after training. During spaced training, escape vanishes and is mainly
      replaced by freezing, while during massed training, escape decreases over trials
      without being replaced by any defensive response. After 24 h, the marked
      proclivity to freezing persists in spaced trained crabs, while a high level of
      escaping is shown by massed trained crabs. The long-lasting freezing preference
      of spaced trained crabs proves to be context-specific and apparent from the very
      first presentation of the danger stimulus at testing, though freezing is not
      triggered by the sole exposure to the context. We conclude (a) that freezing
      preference is the acquired response of the CSM process; (b) that CSM can be
      properly categorized as an instance of contextual conditioning and SM of
      classical habituation; (c) that CSM and SM are not two phases of a memory
      processing but two distinctly types of memory; and (d) that therefore, the
      temporal distribution of training trials has a drastic effect on crab's memory,
      more dramatic than that previously described. The possibility that massed and
      spaced presentations of the same stimulus may represent two different stimulus
      types is discussed.

PMID- 10933899
TI  - Noradrenergic receptor blockade of the NTS attenuates the mnemonic effects of
      epinephrine in an appetitive light-dark discrimination learning task.
AB  - These experiments examined the contribution of noradrenergic neurons in the
      nucleus of the solitary tract (NTS) in mediating the memory-facilitating effects
      of epinephrine. In Experiment 1, saline or 0.05 or 0.1 mg/kg of epinephrine was
      given intraperitoneally (ip) to rats after the second day of training in a light
      dark Y-maze discrimination task. On a 20-trial retention test given 2 and 7 days
      later, the 0.1 mg/kg epinephrine group made significantly more correct responses
      than controls and required fewer trials to reach criterion. In Experiment 2,
      phosphate-buffered saline or the noradrenergic antagonist dl-propranolol (0.3 or
      1.0 microg/0.5 microl) was infused into the NTS prior to an ip injection of
      saline or 0.1 mg/kg of epinephrine. The memory-enhancing effects of epinephrine
      were attenuated by the infusion of 0.3 microg/0.5 microl of dl-propranolol into
      the NTS. These findings indicate an involvement of NTS noradrenergic neurons in
      mediating the effects of peripheral epinephrine on memory storage processes.

PMID- 10933901
TI  - Hippocampal expression of the orphan nuclear receptor gene hzf-3/nurr1 during
      spatial discrimination learning.
AB  - The immediate-early gene hzf-3, also known as nurr1, is a member of the inducible
      orphan nuclear receptor family and is one candidate in the search for genes
      associated with learning and memory processes. Here we report that acquisition of
      a spatial food search task is accompanied by elevated levels of hzf-3 mRNA in the
      hippocampus. Adult male Long-Evans rats were handled, food-restricted, and
      allowed to habituate to the maze prior to training. During acquisition, rats were
      given one training session per day for 5 days. Each training session consisted of
      five trials in which animals searched the maze for food located in 4 of 16 holes
      in the floor of the maze. Training resulted in spatial acquisition of the task.
      Northern blot analysis showed significant increases in hippocampal hzf-3 mRNA 3 h
      after training in the maze. Next, brains were obtained from Naive, Habituated,
      Day 1, Day 3, and Day 5 animals and processed for in situ hybridization. The
      results showed significant increases of hzf-3 mRNA in CA1 and CA3 subregions of
      the dorsal hippocampus during acquisition of the task. We conclude that
      expression of the hzf-3 gene in the brain is associated with long-term spatial
      memory processes. The present results are the first to implicate an orphan
      nuclear receptor in long-term information storage in the hippocampus.

PMID- 10933900
TI  - Glycine(B) receptor antagonists and partial agonists prevent memory deficits in
      inhibitory avoidance learning.
AB  - Activation of N-methyl-d-aspartate (NMDA) receptors has been hypothesized to
      mediate certain forms of learning and memory. This hypothesis is based on the
      ability of competitive and uncompetitive NMDA receptor antagonists to disrupt
      learning. We investigated the effects of glycine site antagonists and partial
      agonists on deficits of acquisition (learning) and consolidation (memory) in a
      single trial inhibitory avoidance learning paradigm. Posttraining administration
      of either hypoxia (exposure to 7% oxygen) or the convulsant drug
      pentylenetetrazole (PTZ) (45 mg/kg) to mice impaired consolidation without
      producing neuronal cell death. Pretreatment with the competitive glycine
      antagonist 7-chlorokynurenic acid (7KYN) and the glycine partial agonists 1
      aminocyclopropanecarboxylic acid (ACPC) and (+)HA-966 prevented memory deficits
      induced by hypoxia and PTZ, but did not affect scopolamine-induced learning
      impairment. In addition, ACPC prevented consolidation deficits evoked by a
      nonexcitotoxic concentration of l-trans-pyrrolidine-2, 4-dicarboxylate, a
      competitive inhibitor of glutamate transport that increases extracellular levels
      of glutamate. Moreover, (+)HA-966, 7KYN, and ACPC facilitated both acquisition
      and consolidation of inhibitory avoidance training, an effect that was dose
      dependent and reversed by glycine. These results indicate that memory deficits
      induced by both hypoxia and PTZ involve NMDA receptor activation. Furthermore,
      the present findings demonstrate that glycine site antagonists and partial
      agonists prevent memory deficits of inhibitory avoidance learning by affecting
      consolidation, but not acquisition processes.

PMID- 10933902
TI  - Gene therapy on the RAC.

PMID- 10933904
TI  - Cystic fibrosis gene therapy trials and tribulations.

PMID- 10933903
TI  - Rational design of viral vectors based on rigorous analysis of capsid structures.

PMID- 10933905
TI  - Policy statement of the American Society of Gene Therapy on reporting of patient
      adverse events in gene therapy trials.

PMID- 10933906
TI  - Changing roles for academia and industry in genetics and gene therapy.

PMID- 10933907
TI  - Tissue engineering.

PMID- 10933908
TI  - Type-specific epitope locations revealed by X-ray crystallographic study of
      adenovirus type 5 hexon.
AB  - A major obstacle to the use of adenovirus as a vector for gene therapy is the
      host immune response to hexon, the major protein component of the icosahedral
      capsid. A solution lies in creating novel vectors with modified or chimeric
      hexons to evade the immune response to native hexon. The crystal structure of
      hexon from human adenovirus type 5 (ad5), the type primarily used for gene
      therapy, has been determined to facilitate the design of such molecules. As the
      951-amino-acid (aa) ad5 hexon sequence is closely related to that of ad2 (967 aa;
      86% aa identity), the ad5 structure was solved by molecular replacement with a
      model constructed from the known ad2 hexon. During refinement, greater than 25%
      of the sequence was reassigned, resulting in a relocation of two epitope regions,
      from buried positions in the ad2 model to external sites at the top of the ad5
      molecule. The resultant model is in better agreement with crystallographic data,
      while maintaining the overall topology of ad2 hexon. This work suggests that all
      hexons have the same basic fold and that the ad5 hexon structure provides an
      accurate and representative model for designing new adenovirus vectors.

PMID- 10933909
TI  - Efficient transduction of nondividing cells by optimized feline immunodeficiency
      virus vectors.
AB  - Second- and third-generation three-plasmid vector systems, termed FELIX, were
      constructed from feline immunodeficiency virus (FIV). To enhance vector
      production, the weak FIV long terminal repeat promoter was replaced with the
      human cytomegalovirus enhancer/promoter. To construct a minimal system in which
      Gag-Pol was the only viral protein present, the cytoplasmic transport element was
      used in place of the FIV Rev-RRE system to facilitate nuclear export of Gag-Pol
      and the transfer vector. Unconcentrated vector titers routinely exceeded 1 x
      10(6) IU/mL for most constructs tested. Second- and optimized third-generation
      vectors were capable of efficiently infecting G1/S- and G2/M-arrested cells. FIV
      based FELIX vectors transduced human dendritic cells, hepatocytes, and aortic
      smooth muscle with efficiencies similar to that of a control 3T3 cell line. All
      three of these primary cell types were transducible by both the second- and third
      generation FELIX vectors, demonstrating that FIV Gag-Pol alone contains the
      determinants necessary for transduction of primary cells. In cross-packaging
      tests, we observed that HIV Gag-Pol does not substantially package FIV vectors;
      consequently, use of such vectors in human immunodeficiency virus-infected cells
      should not lead to efficient mobilization of the inserted gene. Thus, this FIV
      based vector system offers high efficiency and stable delivery of genes to
      numerous nondividing and primary cell types, opening new avenues for biological
      inquiry into normal human cells.

PMID- 10933910
TI  - Free cholesterol enhances adenoviral vector gene transfer and expression in CAR
      deficient cells.
AB  - Efficient adenovirus vector-mediated gene transfer depends on the presence of
      sufficient amounts of the high-affinity coxsackie-adenovirus (Ad) receptor (CAR)
      on the surface of the target cell leading to receptor-mediated endocytosis of the
      vector. The present study evaluates the effect of free cholesterol, a lipid
      component of endocytic vesicles, on Ad uptake into CAR-deficient cells. Infection
      in the presence of free cholesterol at its maximum solubility in water led to
      increased binding, uptake, and expression of Ad in human skin fibroblasts and
      alveolar macrophages, two primary human cells known to be deficient in CAR. The
      effect of free cholesterol was maximal at its solubility maximum in aqueous
      solution. Increase of Ad vector-mediated gene transfer with cholesterol was
      dependent on the lack of CAR receptor expression on the surface and was
      diminished by overexpression of CAR in CAR-deficient cells. Cholesterol-mediated
      increase of Ad-mediated gene expression was dependent on coincubation of both
      cholesterol and Ad and was not dependent on the cholesterol content of the cell.
      Increased Ad vector-mediated gene expression in the presence of free cholesterol
      was also observed in murine skin in vivo. Structural analysis of the Ad
      cholesterol mixture showed complexation between Ad particles leading to formation
      of multivirus aggregates due to hydrophobic interaction. The addition of free
      cholesterol with Ad vectors may be a simple way to increase Ad-mediated gene
      transfer to cells that are poor targets due to their lack of a sufficient number
      of Ad receptors.

PMID- 10933911
TI  - Human T lymphocyte genetic modification with naked DNA.
AB  - Endowing T lymphocytes with novel functional attributes by genetic modification
      is under development for a broad range of clinical cellular immunotherapy
      applications. To circumvent many of the limitations associated with viral vector
      systems, a plasmid-based electroporation system that reliably generates G418
      resistant primary human T lymphocyte clones was developed. TCR alpha/beta+
      CD4+CD8-, and CD4-CD8+ T lymphocyte clones can be routinely isolated from OKT3
      stimulated peripheral blood mononuclear cells electroporated with linear plasmid
      DNA in a limiting dilution drug selection format. Fluorescence in situ
      hybridization (FISH) studies performed on T cell metaphase spreads using a probe
      specific for plasmid sequence demonstrated a single FISH signal doublet that
      varied in chromosomal location from clone to clone. Southern blot analysis using
      a Neo-specific probe verified chromosomal integration of plasmid vector at a
      single site. Band intensity quantitation of blots developed with a zeta-specific
      probe capable of annealing to both endogenous TCR-zeta and the introduced
      chimeric zeta sequence demonstrated that integrated plasmid was present at a
      single copy number. Expression levels of the CD20-specific chimeric
      immunoreceptor construct from a CMV immediate/early promoter present in the
      plasmid vector varied widely from clone to clone but remained stable during ex
      vivo expansion to cell numbers in excess of 10(10). This T lymphocyte genetic
      modification strategy is currently being piloted in a FDA-sanctioned adoptive
      therapy trial for recurrent lymphoma.

PMID- 10933912
TI  - Therapy of head and neck squamous cell carcinoma with an oncolytic adenovirus
      expressing HSV-tk.
AB  - Currently available therapeutic modalities for advanced head and neck squamous
      cell carcinoma (HNSCC), such as radical surgery, high-dose radiotherapy, and
      chemotherapy, are of limited efficacy. Overall survival has not significantly
      improved over the past 30 years; thus, HNSCC represents a promising target for
      new therapeutic approaches, such as gene therapy. A major obstacle to the
      development of effective suicide gene therapy strategies that rely on in situ
      transduction of tumor cells is the poor distribution of the vector throughout the
      tumor. To address this problem we evaluated the use of Ad.OW34, an Elb 55 kD and
      HSV-tk-carrying, replication-competent adenoviral vector that has a wild-type
      adenovirus phenotype in replicating cells, in combination with ganciclovir (GCV)
      as a treatment for HNSCC xenografts in nude mice and compared its efficacy with
      that of a standard replication-deficient adenovirus expressing HSV-tk (Ad.TK). In
      this model, Ad.OW34 had a significantly greater antitumor effect than the
      traditional Ad.TK vector, administered alone or in combination with GCV.
      Interestingly, GCV did not further enhance the oncolytic efficacy of Ad.OW34. GCV
      also aborts viral replication and thus represents a fail-safe feature of this
      vector not found in wild-type adenovirus.

PMID- 10933913
TI  - Long-term and significant correction of brain lesions in adult
      mucopolysaccharidosis type VII mice using recombinant AAV vectors.
AB  - Most lysosomal storage diseases, including mucopolysaccharidosis, affect the
      central nervous system (CNS). They often induce severe and progressive mental
      retardation. Replacement therapy by purified enzyme infusions is a promising
      approach for the treatment of peripheral organs but without effect on CNS
      pathology because the enzyme cannot cross the blood-brain barrier. Intracranial
      injection of recombinant adeno-associated virus (AAV) vectors offers an
      alternative for sustained local enzyme delivery from genetically engineered
      cells. We stereotactically injected an AAV vector containing the human beta
      glucuronidase cDNA into the striatum of adult mice severely affected by
      mucopolysaccharidosis type VII at the time of treatment. Six weeks later, beta
      glucuronidase activity in the injected hemisphere was comparable to that of
      heterozygous mice, which have a normal phenotype. Areas staining positive for
      enzyme activity enlarged with time, representing more than 10% of the hemisphere
      volume by 16 weeks. A complete reversion of lysosomal storage lesions was evident
      in these areas, as well as in most neurons located in surrounding negative areas
      and in the noninjected hemisphere. Thus, a single intracerebral injection of AAV
      vectors could achieve a broad and sustained lysosomal enzyme delivery, allowing
      for stable reversion of storage lesions in a significant fraction of the adult
      brain.

PMID- 10933914
TI  - Connexin 43-enhanced suicide gene therapy using herpesviral vectors.
AB  - Tumor cell transduction with the herpes simplex virus (HSV) thymidine kinase (tk)
      gene and treatment with ganciclovir (GCV) is a widely studied cancer gene
      therapy. Connexin (Cx)-dependent gap junctions between cells facilitate the
      intercellular spread of TK-activated GCV, thereby creating a bystander effect
      that improves tumor cell killing. However, tumor cells often have reduced
      connexin expression, thus thwarting bystander killing and the effectiveness of
      TK/GCV gene therapy. To improve the effectiveness of this therapy, we compared an
      HSV vector (TOCX) expressing Cx43 in addition to TK with an isogenic tk vector
      (TOZ.1) for their abilities to induce bystander killing of Cx-positive U-87 MG
      human glioblastoma cells and Cx-negative L929 fibrosarcoma cells in vitro and in
      vivo. The results showed that low-multiplicity infection of U-87 MG cells with
      TOCX only minimally increased GCV-mediated cell death compared with infection by
      TOZ.1, consistent with the endogenous level of Cx in these cells. In contrast,
      bystander killing of L929 cells was markedly enhanced by vector-mediated
      expression of Cx. In vivo experiments in which U-87 MG cells were preinfected at
      low multiplicity and injected into the flanks of nude mice showed complete cures
      of all animals in the TOCX group following GCV treatment, whereas untreated
      animals uniformly formed fatal tumors. TOCX injection into U-87 MG intradermal
      and intracranial tumors resulted in prolonged survival of the host animals in a
      GCV-dependent manner. Together, these results suggest that the combination of TK
      and Cx may be beneficial for the treatment of human glioblastoma.

PMID- 10933915
TI  - Angiogenesis monitored by perfusion with a space-filling microbead suspension.
AB  - Numerous laboratories are focusing efforts on delivering gene products to induce
      or prevent the development of new blood vessels in adults, with the hope of
      rescuing ischemic tissues, circumventing cardiac bypass surgery, or inhibiting
      tumor growth. Current approaches to the assessment of vascular continuity involve
      the introduction of either dyes or fluorescent microspheres to track blood flow.
      However, dyes and dextrans are subject to leakage when vessels are
      hyperpermeable, a situation that may occur in studies of tumor vasculature and
      during efforts to stimulate therapeutic angiogenesis. Furthermore, the
      microspheres that are used for flow studies do not allow a comprehensive visual
      analysis of vascular continuity. Here we report a method for the visual
      assessment of microvascular continuity in mouse muscle under circumstances in
      which vessels are leaky. The approach involves perfusion of the vasculature with
      fluorescent beads that are much smaller than those used for flow studies. The
      suspension behaves like a fluid and completely fills the vessels, yet the beads
      do not leak from VEGF-permeablized capillaries and remain localized in
      histological sections. Use of beads with the proper fluorescence emission
      wavelengths allows immunofluorescent colocalization with vessel-specific markers.
      We compare this improved method with other methods for tracking vascular
      continuity involving dextrans and larger beads. This approach should aid in the
      dynamic study of tumor angiogenesis and the evaluation of efforts to deliver
      angiogenic factors.

PMID- 10933916
TI  - Improved adeno-associated virus vector production with transfection of a single
      helper adenovirus gene, E4orf6.
AB  - Recent advances in adeno-associated virus (AAV) vector production have eliminated
      the need for adenovirus infection by transfection of plasmids encoding the
      adenovirus E2A, E4orf6, and VA RNA transcription units. We report here the
      generation of significantly higher AAV vector titers with transfection of the
      single adenovirus gene, E4orf6, when used in conjunction with the split AAV
      packaging plasmids MTrep and CMVcap. Transduction in a murine lung model with
      these higher titer vector stocks was greater than that observed with traditional
      preparation methods. The generation of higher titer AAV vector stocks with fewer
      adenovirus gene products and free of replication-competent AAV will enhance the
      potential for AAV in clinical applications.

PMID- 10933917
TI  - Metabolic biotinylation of recombinant proteins in mammalian cells and in mice.
AB  - The avidin-biotin system is a fundamental technology in biomedicine for
      immunolocalization, imaging, nucleic acid blotting, and protein labeling. While
      this technology is robust, it is limited by the fact that mammalian proteins must
      be expressed and purified prior to chemical biotinylation using cross-linking
      agents which modify proteins at random locations to heterogeneous levels and can
      inactivate protein function. To circumvent this limitation, we demonstrate the
      ability to metabolically biotinylate tagged proteins in mammalian cells and in
      mice using the endogenous biotinylation enzymes of the host. Endogenously
      biotinylated proteins were readily purified from mammalian cells using monomeric
      avidin and eluted under nondenaturing conditions using only biotin as the
      releasing agent. This technology should allow recombinant proteins and fragile
      protein complexes to be produced and purified from mammalian cells as well as
      from transgenic plants and animals. In addition, this technology may be
      particularly useful for cell-targeting applications in which proteins or viral
      gene therapy vectors can be biotinylated at genetically defined sites for
      combination with other targeting moieties complexed with avidin.

PMID- 10933919
TI  - Modern Medicine, a Young Society, and a New Journal.

PMID- 10933918
TI  - Safety and biological efficacy of a lipid-CFTR complex for gene transfer in the
      nasal epithelium of adult patients with cystic fibrosis.
AB  - Gene transfer is an attractive option to treat the basic defect in cystic
      fibrosis. In a double-blind, placebo-controlled, rising-dose tolerance study in
      the nasal epithelium, we tested the safety and efficacy of a cationic liposome [p
      ethyl-dimyristoylphosphadityl choline (EDMPC) cholesterol] complexed with an
      expression plasmid containing hCFTR cDNA. Eleven adult CF patients were studied
      in a protocol that allowed comparisons within individual subjects: vector and
      placebo were sprayed into alternate nostrils at intervals over 7 h. After dosing,
      vector-specific DNA was present in nasal lavage of all subjects for up to 10
      days. There were no adverse events. The vector-treated epithelium did not exhibit
      a significant increase in CFTR-mediated Cl- conductance from baseline and was not
      different from the placebo-treated nostril: mean deltaCFTR Cl- conductance, mV +/
      SEM, -1.6+/-0.4 vs -0.6+/-0.4, respectively. CFTR-mediated Cl- conductance
      increased toward normal during repetitive nasal potential difference measurements
      over the 3 days before dosing which influenced the postdosing calculations. No
      vector-specific mRNA was detected in the nasal epithelial scrape biopsies,
      although endogenous CFTR mRNA was detected in all subjects. We conclude that the
      lipid-DNA complex is safe, but did not produce consistent evidence of gene
      transfer to the nasal epithelium by physiologic or molecular measures.

PMID- 10933920
TI  - A "friendly merger" in the war on cancer.

PMID- 10933921
TI  - Targeting gene therapy--a reality?

PMID- 10933922
TI  - Rescue of skeletal muscles of gamma-sarcoglycan-deficient mice with adeno
      associated virus-mediated gene transfer.
AB  - In humans, a subset of cases of Limb-girdle muscular dystrophy (LGMD) arise from
      mutations in the genes encoding one of the sarcoglycan (alpha, beta, gamma, or
      delta) subunits of the dystrophin-glycoprotein complex. While adeno-associated
      virus (AAV) is a potential gene therapy vector for these dystrophies, it is
      unclear if AAV can be used if a diseased muscle is undergoing rapid degeneration
      and necrosis. The skeletal muscles of mice lacking gamma-sarcoglycan (gsg-/-
      mice) differ from the animal models that have been evaluated to date in that the
      severity of the skeletal muscle pathology is much greater and more representative
      of that of humans with muscular dystrophy. Following direct muscle injection of a
      recombinant AAV [in which human gamma-sarcoglycan expression is driven by a
      truncated muscle creatine kinase (MCK) promoter/enhancer], we observed
      significant numbers of muscle fibers expressing gamma-sarcoglycan and an overall
      improvement of the histologic pattern of dystrophy. However, these results could
      be achieved only if injections into the muscle were prior to the development of
      significant fibrosis in the muscle. The results presented in this report show
      promise for AAV gene therapy for LGMD, but underscore the need for intervention
      early in the time course of the disease process.

PMID- 10933923
TI  - The TRAIL decoy receptor TRUNDD (DcR2, TRAIL-R4) is induced by adenovirus-p53
      overexpression and can delay TRAIL-, p53-, and KILLER/DR5-dependent colon cancer
      apoptosis.
AB  - The cell surface decoy receptor proteins TRID (also known as DcR1 or TRAIL-R3)
      and TRUNDD (DcR2, TRAIL-R4) inhibit caspase-dependent cell death induced by the
      cytotoxic ligand TRAIL in part because of their absent or truncated cytoplasmic
      death domains, respectively. We previously identified the death domain containing
      proapoptotic TRAIL death receptor KILLER/DR5 (TRAIL-R2) as an upregulated
      transcript following exposure of cancer cells, with wild-type but not with mutant
      or degraded p53 proteins, to a cytotoxic dose of adriamycin. In the present
      studies we provide evidence that expression of the TRAIL decoy receptors TRUNDD
      and TRID increases following infection of cancer cells with p53-expressing
      adenovirus (Ad-p53), in a manner similar to other p53 target genes such as
      KILLER/DR5 and p21WAF1/CIP1. Subsequent overexpression of TRUNDD in colon cancer
      cell lines caused a significant delay in killing induced by TRAIL. Furthermore,
      cotransfection of TRUNDD with either p53 or KILLER/DR5 (at a 4:1 DNA ratio) in
      colon cancer cells decreased cell death caused by either gene. This protective
      effect of TRUNDD was not dependent on the presence of TRAIL, and overexpression
      of TRUNDD did not alter the protein levels of either p53 or KILLER/ DR5. Further
      deletion studies showed that whereas protection by TRUNDD against TRAIL-mediated
      apoptosis did not require an intact intracellular domain (ICD), the first 43
      amino acids of the ICD of TRUNDD were needed for protection against cell death
      induced by p53 or KILLER/DR5. Our results suggest a model in which the TRAIL
      decoy receptors may be induced by p53, thereby attenuating an apoptotic response
      that appears to involve KILLER/DR5. Therefore, the p53-dependent induction of
      TRUNDD may provide a mechanism to transiently favor cell survival over cell
      death, and overexpression of TRUNDD may be another mechanism of escape from p53
      mediated apoptosis in gene therapy experiments.

PMID- 10933924
TI  - Lymphoid development and function in X-linked severe combined immunodeficiency
      mice after stem cell gene therapy.
AB  - Mutations of the common gamma chain (gammac) of cytokine receptors cause X-linked
      severe combined immunodeficiency (XSCID), a candidate disease for gene therapy.
      Using an XSCID murine model, we have tested the feasibility of stem cell gene
      correction. XSCID bone marrow (BM) cells were transduced with a retroviral vector
      expressing the murine gammac (mgammac) and engrafted in irradiated XSCID animals.
      Transplanted mice developed mature B cells, naive T cells, and mature natural
      killer (NK) cells, all of which were virtually absent in untreated mice. The
      mgammac transgene was detected in all treated mice, and we could demonstrate
      mgammac expression in newly developed lymphocytes at both the RNA and protein
      level. In addition, treated mice showed T cell proliferation responses to
      mitogens and production of antigen-specific antibodies upon immunization. Four of
      seven treated animals showed a clear increase of the transgene positive cells,
      suggesting in vivo selective advantage for gene-corrected cells. Altogether,
      these results show that retroviral-mediated gene transfer can improve murine
      XSCID and suggest that similar strategies may prove beneficial in human clinical
      trials.

PMID- 10933925
TI  - Sustained expression of therapeutic level of factor IX in hemophilia B dogs by
      AAV-mediated gene therapy in liver.
AB  - We demonstrate that a single intraportal vein injection of a recombinant adeno
      associated virus (rAAV) vector encoding canine factor IX (cFIX) cDNA under the
      control of a liver-specific enhancer/promoter leads to a long-term correction of
      the bleeding disorder in hemophilia B dogs. Stable expression of the therapeutic
      level of cFIX (5% of normal level) was detected in the plasma of a dog injected
      with an AAV vector at a dose of 4.6 x 10(12) particles/kg for over 7 months. Both
      whole-blood clotting time (WBCT) and activated partial thromboplastin time (aPTT)
      of the treated dogs have been greatly decreased since the treatment. No anti
      canine factor IX antibodies have been detected in the treated animals.
      Importantly, no bleeding has been observed in the dog that expresses a
      therapeutic level of cFIX for 7 months following vector administration. Moreover,
      no persistent significant hepatic enzyme abnormalities were detected in the
      treated dogs. Thus, a single intraportal injection of a rAAV vector expressing
      cFIX successfully corrected the bleeding disorder of hemophilia B dogs,
      supporting the feasibility of using AAV-based vectors for liver-targeted gene
      therapy of genetic diseases.

PMID- 10933926
TI  - Adenovirus-mediated inducible gene expression in vivo by a hybrid ecdysone
      receptor.
AB  - Precise control of transgene expression would markedly facilitate certain
      applications of gene therapy. To regulate expression of a transferred gene in
      response to an exogenous compound in vivo, we modified the ecdysone-responsive
      system. We combined the advantages of the Drosophila (DmEcR) and the Bombyx
      ecdysone receptor (BmEcR) by creating a chimeric Drosophila/Bombyx ecdysone
      receptor (DB-EcR) that preserved the ability to bind to the modified ecdysone
      promoter without exogenous retinoid X receptor (RXR). In cultured cells, DB-EcR
      effectively mediates ligand-dependent transactivation of a reporter gene at lower
      concentrations of the chemical ecdysone agonist GS-E than VgRXR (DmEcR + RXR).
      Transgene delivery in vivo was achieved by intramyocardial injection of
      recombinant adenovirus vectors in adult rats. Upon stimulation with GS-E, DB-EcR
      potently (>40-fold induction) activated gene expression in vivo while VgRXR was
      not induced. This hybrid ecdysone receptor represents an important new tool for
      in vivo transgene regulation with potentially diverse applications in somatic and
      germline transfer.

PMID- 10933927
TI  - Intrakines--evidence for a trans-cellular mechanism of action.
AB  - Human CXCR4 is the receptor for the CXC chemokine SDF-1alpha and also acts as a
      coreceptor for T lymphotropic HIV-1 strains. Blocking the surface expression of
      this receptor via an intrakine approach has recently been shown to efficiently
      prevent HIV-1 infection of T cells. The CXC-chemokine gene is fused to an
      endoplasmic reticulum retention signal (KDEL) that retains the newly synthesized
      chemokine and its receptor within the cell, where both are subsequently degraded.
      We constructed MoMuLV-based vectors containing the SDF-KDEL construct driven by
      the "MND" long terminal repeat, using eGFP as a marker gene (MND-SDF-KDEL-IRES
      eGFP) and a control vector (MND-X-IRES-eGFP). CEM human T lymphoblastic leukemia
      cells were transduced with the intrakine vector or the control vector. We
      detected a marked downregulation of CXCR4 expression in the cells transduced with
      the intrakine vectors as opposed to the cells transduced with the control vector.
      However, the eGFP-negative fraction of the cells transduced with the intrakine
      vector displayed the same CXCR4 downregulation as the eGFP-positive fraction,
      suggesting an effect in trans. The possibility of this being due to eGFP being
      silenced while SDF-KDEL was still expressed was excluded by Southern and Northern
      blot analyses. Upon cultivating the control cells with supernatant of the cells
      transduced with the intrakine vector, we observed a downregulation of CXCR4
      expression on the control cells. Experiments using rhSDF-1alpha showed
      downregulation by the supernatant to be comparable to that achieved by the
      exogenous addition of 30 ng/ml SDF-1alpha. To assess the bioactivity of the
      secreted substance in the supernatant, a chemotaxis assay was performed. The
      transmigration observed was, once again, within the range of that achieved by the
      addition of 30 ng/ml SDF-1alpha. We conclude that the intrakine SDF-KDEL, apart
      from acting within the cell, is also in part secreted and causes the
      downregulation of the receptor by acting like a secreted chemokine.

PMID- 10933928
TI  - Transduction of human PBMC-derived dendritic cells and macrophages by an HIV-1
      based lentiviral vector system.
AB  - Professional antigen-presenting cells, such as dendritic cells (DCs) and
      macrophages, are target cells for gene therapy of infectious disease and cancer.
      However, transduction of DCs and macrophages has proved difficult by most
      currently available gene transfer methods. Several recent studies have shown that
      lentiviral vector systems can efficiently transduce many nondividing and
      differentiated cell types. In this study, we examined the gene transfer to DCs
      and macrophages using a lentiviral vector system. Human DCs were propagated from
      the adherent fraction of peripheral blood mononuclear cells (PBMCs) by culture in
      medium containing GM-CSF, IL-4, and TNF-alpha. Human macrophages were propagated
      from adherent PBMCs in medium containing GM-CSF. High titers of a replication
      defective vesicular stomatitis virus glycoprotein G pseudotyped HIV-1-based
      vector encoding the enhanced yellow fluorescent protein were produced. In
      immature DCs (culture days 3 and 5), transduction efficiencies of 25 to 35% were
      achieved at a multiplicity of infection of 100. However, the transduction
      efficiency was decreased in more mature DCs (culture day 8 or later).
      Furthermore, monocyte-derived macrophages were also transduced by the lentiviral
      vector system. In addition, Alu-LTR PCR demonstrated the integration of the HIV-1
      provirus into the cellular genome of the transduced DCs and macrophages.
      Allogeneic mixed lymphocyte reactions revealed similar antigen-presenting
      functions of untransduced and lentivirally transduced DCs. Thus, the results of
      this study demonstrate that both PBMC-derived DCs and macrophages can be
      transduced by lentiviral vectors.

PMID- 10933929
TI  - Aerosol delivery of robust polyethyleneimine-DNA complexes for gene therapy and
      genetic immunization.
AB  - Aerosol delivery of plasmid DNA to the lungs offers the possibility of direct
      application of gene preparations to pulmonary surfaces as a means of treating a
      variety of genetic pulmonary disorders. However, the process of jet nebulization
      rapidly degrades naked DNA, viral vectors, and many lipid-based formulations.
      While complexing DNA with cationic lipids has been shown to significantly
      stabilize plasmid DNA, losses of biological activity often occur during
      nebulization, severely limiting the efficiency of aerosol delivery of many such
      complexes. In conjunction with the design of aerosol delivery systems appropriate
      for DNA delivery, we have developed formulations using polyethyleneimine (PEI, a
      polycationic polymer) and DNA that result in a high level of pulmonary
      transfection (10- to 100-fold greater than many cationic lipids) and are stable
      during nebulization. In addition, these PEI-based formulations exhibit a high
      degree of specificity for the lungs. The properties of PEI-based formulations
      that make them resistant to nebulization and efficient as DNA delivery vectors
      for pulmonary sites have been investigated. Potential applications of this
      technology, including the use of aerosolized PEI-DNA for genetic immunization,
      are discussed.

PMID- 10933930
TI  - Hepatic expression of apolipoprotein E inhibits progression of atherosclerosis
      without reducing cholesterol levels in LDL receptor-deficient mice.
AB  - Apolipoprotein E (apoE) is a multifunctional protein synthesized by the liver and
      by tissue macrophages. Plasma apoE (derived primarily from the liver) regulates
      plasma lipoprotein metabolism, but macrophage-derived apoE was shown to slow the
      progression of atherosclerosis independent of plasma lipid levels. We utilized
      liver-directed gene transfer to test the hypothesis that hepatic expression of
      human apoE would inhibit atherogenesis even in a model in which apoE expression
      has little effect on plasma lipoproteins. LDL receptor-deficient mice fed a
      western-type diet for 5 weeks were injected with a second-generation recombinant
      adenovirus encoding human apoE3 or control virus. Plasma cholesterol levels were
      not significantly different in the two groups of mice after virus injection. Four
      weeks after injection, atherosclerosis was examined using three independent
      assays. Expression of apoE was associated with significantly reduced
      atherosclerosis compared with control mice in both the aortic arch (decreased by
      43%) and the aortic root (decreased by 59%). In summary, hepatic overexpression
      of apoE inhibited progression of atherosclerosis in LDL receptor-deficient mice
      without reducing plasma cholesterol levels. This finding indicates that liver
      derived plasma apoE can influence early atherogenesis through mechanisms other
      than modulation of lipoprotein metabolism and that liver-directed gene transfer
      and overexpression of apoE may be a therapeutic approach to atherosclerosis.

PMID- 10933931
TI  - Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir
      administration in patients with current malignant brain tumors.
AB  - Between December 1996 and September 1998, 13 patients with advanced recurrent
      malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3
      with anaplastic astrocytoma) were treated with a single intratumoral injection of
      2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a
      replication-defective adenoviral vector bearing the herpes simplex virus
      thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk),
      followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was
      20:1. Our primary objective was to determine the safety of this treatment.
      Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely
      tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited
      central nervous system toxicity with confusion, hyponatremia, and seizures. One
      patient is living and stable 29.2 months after treatment. Two patients survived
      >25 months before succumbing to tumor progression. Ten patients died within 10
      months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis.
      Neuropathologic examination of postmortem tissue demonstrated cavitation at the
      injection site, intratumoral foci of coagulative necrosis, and variable
      infiltration of the residual tumor with macrophages and lymphocytes.

PMID- 10933932
TI  - Painful lessons.

PMID- 10933933
TI  - Reports of adenovector "death" are greatly exaggerated.

PMID- 10933934
TI  - Gene therapy for hemophilia: a step closer to reality.

PMID- 10933935
TI  - Minding the Cs and Gs.

PMID- 10933936
TI  - Gene therapy as drug development.

PMID- 10933937
TI  - Progress and potential for gene-based medicines.
AB  - During the past decade researchers have explored the potential of gene-based
      medicines to extend current treatments employing chemical entities and proteins.
      However, progress has been slower than was originally predicted due to our
      limited knowledge of the genetic components of major diseases, the complexity of
      developing active biological agents as therapies, and the stringent and time
      consuming tests necessary to ensure safety prior to introduction of these novel
      modalities in the clinic. In spite of the present technology challenges and
      clinical setbacks in gene therapy it is anticipated that gene-based medicines
      will find their niche in disease prevention and management strategies in the
      coming decade, extending the repertoire of medicines available to satisfy key
      unmet medical needs. Additionally, progress in xenotransplantation research is
      creating the opportunity to use gene-modified porcine organs for human
      transplantation. This innovative approach aims to address the current
      insufficiency of human donor organs for clinical transplantation.

PMID- 10933938
TI  - Role of vector in activation of T cell subsets in immune responses against the
      secreted transgene product factor IX.
AB  - Defining immune responses against the secreted transgene product in a gene
      therapy setting is critical for treatment of genetic diseases such as hemophilia
      B (coagulation factor IX deficiency). We have previously shown that intramuscular
      administration of an adeno-associated viral (AAV) vector results in stable
      expression of therapeutic levels of factor IX (F.IX) and may be associated with
      humoral immune responses against F.IX. This study demonstrates that intramuscular
      injection of an AAV vector expressing F.IX fails to activate F.IX-specific
      cytotoxic T lymphocytes (CTLs) in hemostatically normal or in hemophilia B mice,
      so that there is an absence of cellular immune responses against F.IX. However,
      transgene-derived F.IX can cause B cell responses characterized by production of
      T helper cell-dependent antibodies (predominantly IgG1, but also IgG2 subclasses)
      resulting from activation of CD4+ T helper cells primarily of the Th2 subset. In
      contrast, administration of an adenoviral vector efficiently activated F.IX
      specific CTLs and T helper cells of both Th1 and Th2 subsets, leading to
      inflammation and destruction of transduced muscle tissue and activation of B
      cells as well. Therefore, vector sequences fundamentally influence T cell
      responses against transgene-encoded F.IX. In conclusion, activation of the immune
      system in AAV-mediated gene transfer is restricted to pathways mediated by F.IX
      antigen presentation through MHC class II determinants resulting in T and B cell
      responses that are more comparable to responses in the setting of protein
      infusion rather than of viral infection/gene transfer.

PMID- 10933939
TI  - Targeted delivery of plasmid DNA to myogenic cells via transferrin-conjugated
      peptide nucleic acid.
AB  - We describe a novel approach to conjugate a targeting ligand to plasmid DNA
      without affecting either its supercoiled conformation or its ability to be
      efficiently transcribed. A 14-mer peptide nucleic acid (PNA) containing lysine
      and cysteine on each end was designed to target to a unique sequence located at
      the antibiotic resistance gene of the plasmid. The binding of PNA to the plasmid
      was found to be dose-dependent and sequence-specific and not to change the
      conformation of the plasmid. Transferrin (Tf) was conjugated with PNA via a
      reversible disulfide bond using N-succinimidyl-3-(2-pyridyldithio)propionate. Tf
      PNA retained the ability to the plasmid in a sequence-specific manner. The
      efficiency of this bioconjugate for delivering plasmid was examined in cultured
      myoblasts and myotubes. Naked DNA and Tf-PNA/DNA showed no transfection activity
      in either myoblasts or myotubes. Polyethyleneimine (PEI) is required for
      significant increase of the transfection efficiency. At N:P ratio of 5, Tf-PNA
      enhanced gene transfection about fourfold over that of the DNA/PEI complex in
      both myoblasts and myotubes. This enhancement could be inhibited by excess free
      Tf, indicating that the enhancement of transfection was through Tf-mediated
      endocytosis. These findings suggest that this targeting system may have the
      potential for gene transfer to myogenic cells in vivo.

PMID- 10933940
TI  - Characterization of anti-CCR5 ribozyme-transduced CD34+ hematopoietic progenitor
      cells in vitro and in a SCID-hu mouse model in vivo.
AB  - The cellular entry of HIV is mediated by the specific interaction of viral
      envelope glycoproteins with the cell-surface marker CD4 and a chemokine receptor
      (CCR5 or CXCR4). Individuals with a 32-base-pair (bp) deletion in the CCR5 coding
      region, which results in a truncated peptide, show resistance to HIV-1 infection.
      This suggests that the downregulation of CCR5 expression on target cells may
      prevent HIV infection. Therefore, ribozymes that inhibit the CCR5 expression
      offer a novel approach for anti-HIV gene therapy. To assess the effect of an anti
      CCR5 ribozyme (R5Rbz) on macrophage differentiation, CD34+ hematopoietic
      progenitor cells were transduced with a retroviral vector carrying RSRbz and
      allowed to differentiate in the presence of appropriate cytokines. R5Rbz
      transduced CD34+ cells differentiated normally into mature macrophages that
      carried CD14 and CD4 surface markers, expressed the anti-CCR5 ribozyme, and
      showed significant resistance to viral infection upon challenge with the HIV-1
      BaL strain. Using an in vivo thymopoiesis model, the effect of RSRbz on stem cell
      differentiation into thymocytes was evaluated by reconstituting SCID-hu mice
      thymic grafts with ribozyme-transduced CD34+ cells. FACS analysis of cell
      biopsies at 4 and 6 weeks postengraftment for HLA, CD4, and CD8 markers showed
      comparable levels of reconstitution and similar percentages of subpopulations of
      thymocytes between grafts receiving R5Rbz-transduced and control CD34+ cells. RT
      PCR assays demonstrated the expression of the anti-CCR5 ribozyme in CD4+, CD8+,
      and CD4+/CD8+ thymocyte subsets derived from RSRbz-transduced CD34+ cells. These
      results indicate that anti-CCR5 ribozyme can be introduced into hematopoietic
      stem cells without adverse effects on their subsequent lineage-specific
      differentiation and maturation. The expression of anti-CCR5 ribozymes in HIV-1
      target cells offers a novel gene therapy strategy to control HIV infection.

PMID- 10933941
TI  - Reduced inflammatory response to plasmid DNA vectors by elimination and
      inhibition of immunostimulatory CpG motifs.
AB  - An inflammatory response is invariably associated with administration of gene
      transfer complexes composed of cationic lipids and plasmid DNA (pDNA). In the
      lung, an influx of neutrophils and elevated levels of several proinflammatory
      cytokines such as TNF-alpha, IFN-gamma, IL-6, and IL-12 characterize this dose
      dependent response. The induction of these cytokines was shown previously to be
      due in part to the presence of unmethylated CpG dinucleotides in the bacterially
      derived pDNA. We have eliminated 270 of 526 CpG dinucleotides in a reporter
      plasmid (pCFA-CAT) and tested the inflammatory response to cationic lipid:pDNA
      complexes containing the modified vector (pGZA-CAT) after intravenous (i.v.) or
      intranasal (i.n.) delivery into BALB/c mice. Compared to the unmodified vector,
      the CpG-reduced pGZA-CAT was found to be significantly less immunostimulatory, as
      the levels of IL-12, IFN-gamma, and IL-6 in the serum 24 h after i.v. delivery
      were reduced by 40 to 75%. Similar reductions in cytokine levels were also
      observed in the bronchoalveolar lavage fluids (BALF) after i.n. administration,
      while the levels of reporter gene expression were not affected by the
      modifications. We have also investigated known inhibitors of the CpG signaling
      pathways in order to decrease the inflammatory response. Two such inhibitors,
      chloroquine and quinacrine, greatly reduced the induction of IL-12 from mouse
      spleen cells in vitro and inhibited cytokine production in the lung by
      approximately 50% without affecting gene expression. These results illustrate
      that use of a less immunostimulatory pDNA vector or inhibitors of CpG
      immunostimulation can reduce significantly the toxicity associated with cationic
      lipid:pDNA complexes thereby increasing the therapeutic index of this synthetic
      gene transfer vector.

PMID- 10933942
TI  - Evaluation of the biodistribution, persistence, toxicity, and potential of germ
      line transmission of a replication-competent human adenovirus following
      intraprostatic administration in the mouse.
AB  - Adenovirus-mediated gene transfer may hold much promise in the treatment of human
      cancer. However, concerns regarding vector dissemination beyond the target
      tissue, particularly with replication-competent viruses, require an evaluation of
      the persistence of viral infection in collateral tissue and vector-associated
      toxicities. In addition, for indications such as prostate cancer, the proximity
      of the point of viral administration to organs of the male reproductive system
      raises concerns regarding inadvertent germ-line transmission of genes carried by
      the virus. To address these concerns, the biodistribution, persistence, toxicity,
      and potential of germ-line transmission of a replication-competent adenovirus
      (Ad5-CD/TKrep) following intraprostatic administration in the mouse was examined.
      Ad5-CD/TKrep (10(10) vp, 5 x 10(11) vp/kg) was injected intraprostatically on Day
      1 of the study and its presence in the major organs of the male urogenital tract
      (prostate, testes, seminal vesicles, and urinary bladder) and liver was
      determined on Days 8 and 29. For comparison, a parallel group of animals was
      injected with the same dose of a related replication-defective Ad5-FGNR virus. To
      evaluate germ-line transmission, Ad5-CD/TKrep-injected males were mated to
      females on Days 8 and 29 and resulting embryos were examined for AdS-CD/TKrep
      viral DNA. Ad5-CD/TKrep viral DNA was detected in all major organs of the adult
      male urogenital tract and liver 7 and 28 Days postinjection. Interestingly,
      relative to the replication-defective Ad5-FGNR adenovirus, the replication
      competent Ad5-CD/TKrep virus accumulated to a much greater level (approximately
      300-fold) and persisted for a longer period of time in prostate, testes, and
      liver. This difference could not be explained on the basis of differences in
      viral infectivity, suggesting that the AdS-CD/TKrep virus may be capable of
      replicating in mouse tissues in vivo. In vitro infection of six mouse cell lines
      representing prostate, testes, and liver demonstrated that the Ad5-CD/TKrep virus
      was indeed capable of replicating in these mouse cell types, albeit with reduced
      efficiencies relative to human cells. Despite the fact that the Ad5-CD/TKrep
      vector persisted in the adult male gonads and may have replicated in vivo, we
      observed no evidence of germ-line transmission in 149 offspring examined. To
      evaluate the toxicity of combining Ad5-CD/TKrep viral therapy with CD/5-FC and
      HSV-1 TK/GCV suicide gene therapies as a prerequisite for a human trial, an
      escalating dose (10(8), 10(9), 10(10) vp) of Ad5-CD/TKrep was administered
      intraprostatically followed by 7 days of 5-FC and GCV double prodrug therapy.
      Although the virus persisted in the mouse urogenital tract and liver for up to 28
      days postinjection, most of the toxicities observed were expected, minimal, and
      self-limiting. These results lead us to believe that intraprostatic
      administration of the Ad5-CD/TKrep virus to humans concomitant with double
      suicide gene therapy will be associated with acceptable toxicities and will not
      result in vertical transmission of viral-encoded genes through the germ line.

PMID- 10933943
TI  - Immunogene therapy for murine melanoma using recombinant adenoviral vectors
      expressing melanoma-associated antigens.
AB  - Adenoviral vectors expressing tumor-associated antigens can be used to evoke a
      specific immune response and inhibit tumor growth. In this study, we tested the
      efficacy of adenoviral vectors encoding human gp100 (Ad2/hugp100), murine gp100
      (Ad2/mugp100), or murine TRP-2 (Ad2/muTRP-2) for their ability to elicit a
      specific cellular immune response and inhibit the growth of B16 melanoma tumor
      cells in the mouse. C57BL/6 mice were immunized with Ad2/hugp100, Ad2/mugp100, or
      Ad2/muTRP-2 either 2 weeks prior to B16-F10 tumor challenge (prophylactic
      treatment) or 3 days after tumor challenge (active treatment). Ad2/hugp100 and
      Ad2/muTRP-2 administered to two or more intradermal (i.d.) sites inhibited
      subsequent subcutaneous tumor growth in > or = 80% of the mice and elicited an
      antigen-specific cytotoxic T lymphocyte response, whereas other administration
      routes were not as effective. Ad2/mugp100 administered to two i.d. sites did not
      inhibit tumor growth or provoke cellular immunity. Immunization was less
      effective with active treatment where tumor growth was not significantly
      inhibited by a single dose of either Ad2/muTRP-2 or Ad2/hugp100. However,
      increasing the number of intradermal immunization sites and the number of doses
      resulted in progressive improvements in protection from tumor growth in the
      active treatment model. In conclusion, breaking host tolerance to elicit
      protective immunity by using adenoviral vectors expressing melanoma-associated
      antigens is dependent upon the choice of antigen, the site of administration, and
      the number of doses. These observations provide insights into the clinical
      applicability of adenoviral vaccines for immunotherapy of malignant diseases.

PMID- 10933944
TI  - Prolonged high-level detection of retrovirally marked hematopoietic cells in
      nonhuman primates after transduction of CD34+ progenitors using clinically
      feasible methods.
AB  - Low-level retroviral transduction and engraftment of hematopoietic long-term
      repopulating cells in large animals and humans remain primary obstacles to the
      successful application of hematopoietic stem cell (HSC) gene transfer in humans.
      Recent studies have reported improved efficiency by including stromal cells
      (STR), or the fibronectin fragment CH-296 (FN), and various cytokines such as
      flt3 ligand (FLT) during ex vivo culture and transduction in nonhuman primates.
      In this work, we extend our studies using the rhesus competitive repopulation
      model to further explore optimal and clinically feasible peripheral blood (PB)
      progenitor cell transduction methods. First, we compared transduction in the
      presence of either preformed autologous STR or immobilized FN. Long-term
      clinically relevant gene marking levels in multiple hematopoietic lineages from
      both conditions were demonstrated in vivo by semiquantitative PCR, colony PCR,
      and genomic Southern blotting, suggesting that FN could replace STR in ex vivo
      transduction protocols. Second, we compared transduction on FN in the presence of
      IL-3, IL-6, stem cell factor (SCF), and FLT (our best cytokine combination in
      prior studies) with a combination of megakaryocyte growth and development factor
      (MGDF), SCF, and FLT. Gene marking levels were equivalent in these animals, with
      no significant effect on retroviral gene transfer efficiency assessed in vivo by
      the replacement of IL-3 and IL-6 with MGDF. Our results indicate that SCF/G-CSF
      mobilized PB CD34+ cells are transduced with equivalent efficiency in the
      presence of either STR or FN, with stable long-term marking of multiple lineages
      at levels of 10-15% and transient marking as high as 54%. These results represent
      an advance in the field of HSC gene transfer using methods easily applied in the
      clinical setting.

PMID- 10933946
TI  - A matter of trust.

PMID- 10933945
TI  - Discordance between expression and genome transfer titering of HSV amplicon
      vectors: recommendation for standardized enumeration.
AB  - Herpes simplex virus-derived amplicon vectors are well suited to the development
      of gene-based therapy for neurodegenerative diseases. The plasmid-based amplicon
      vector system allows for facile introduction of transcription units, possesses
      the potential for carrying gene inserts up to approximately 130 kb in length, and
      can be packaged into infectious virus devoid of contaminating cytotoxic helper
      virus. For accurate assessments to be made regarding vector comparison and
      improvements in vector design, a standard for titering prepared virus stocks must
      be established. At present, packaged amplicon vectors are routinely titered using
      reporter gene expression units to quantitate numbers of infectious amplicon
      virions. The strength of the promoter, sensitivity of detection of the gene
      product, and choice of titering cell type can greatly influence the apparent
      numbers of infectious virus particles. This is especially evident when
      comparisons are made between two amplicon vectors that possess different
      promoters. To this end, we have developed a new titering method based on a real
      time quantitative PCR technique that allows for enumeration of transducing
      particles. This new approach ensures that amplicon comparison experiments are
      initiated with equivalent transduction units, thus allowing for a fair assessment
      of expression and therapeutic efficacy differences.

PMID- 10933947
TI  - Fluorescence methods reveal intracellular trafficking of gene transfer vectors:
      the light toward the end of the tunnel.

PMID- 10933948
TI  - Immunobiology and the future of myoblast transfer therapy.
AB  - Myoblast transfer therapy (MTT) is a cell-mediated gene transfer method aimed at
      the restoration of normal dystrophin expression in Duchenne muscular dystrophy
      (DMD). Initial clinical MTT trials were conducted amid much controversy, as they
      were based on very few animal studies. Unfortunately, the trials were of little
      therapeutic benefit. As a result, there has been a renaissance of interest in
      experimental studies in animal models. In MTT, myoblasts are obtained by muscle
      biopsy from normal, i.e., dystrophin-positive, donors, expanded in culture, and
      injected directly into the muscles of dystrophic recipients. The major
      requirement for successful MTT is the survival of injected donor myoblasts in the
      host environment. However, a vast majority of donor cells fail to survive for
      more than 1 h after injection, and very few last beyond the first week. This
      review on the immunological aspects of MTT focuses in particular on the roles of
      specific components of the host immune response, the effects of tissue culture on
      donor cells, and strategies under development to circumvent the problem of donor
      myoblast death after injection in vivo.

PMID- 10933949
TI  - Stable transduction of actively dividing cells via a novel adenoviral/episomal
      vector.
AB  - Many gene therapy indications would benefit from vectors capable of achieving
      efficient in vivo delivery and long-term transgene expression in either dividing
      or nondividing cells. Such vector systems are not yet available. To achieve both
      goals, we have used noncytotoxic E1- and E4-deleted adenoviral vectors as
      vehicles for delivering an Epstein-Barr virus-based self-replicating episome
      (replicon) via Cre/loxP site-specific recombination. Co-infection of human cells
      with a proreplicon-encoded and a Cre-expressing adenovirus resulted in efficient
      delivery and excision of a functional replicon in the absence of vector-induced
      cytotoxicity. In addition, replication and nuclear retention of the replicon in
      the cell progeny translated into a prolonged transgene expression in actively
      dividing cells, both in vitro and in vivo. Combining desired features from
      different viruses within a single hybrid vector system should expand the range of
      clinical indications currently amenable to gene transfer.

PMID- 10933950
TI  - Route of administration determines induction of T-cell-independent humoral
      responses to adeno-associated virus vectors.
AB  - Vectors based on adeno-associated viruses (AAV) type 2 show promise for treating
      chronic diseases because transgene expression appears to be stable. This study
      evaluated the impact of humoral immunity to the capsid proteins on vector uptake
      by hepatocytes following an intravascular approach. Route of vector
      administration in mice had a qualitative effect on antivector B cell responses.
      Administration of vector into the tail vein resulted in T-cell-dependent (TD) B
      cell responses that were completely inhibited with depleting CD4 antibody.
      Delivery of vector into the portal circulation via the spleen yielded B cell
      response that were partially T cell independent (TI) rendering strategies based
      on T cell inhibition ineffective in allowing vector readministration. The TI B
      cell response was short lived in comparison to the TD response. Rhesus monkeys
      produced a B cell memory response to intraportal vector which appeared to be T
      cell dependent based on Ig isotypes. Gene therapy strategies that require AAV
      vector readministration should consider vector biodistribution and its impact on
      B cell activation.

PMID- 10933951
TI  - Superior transduction of mouse hematopoietic stem cells with 10A1 and VSV-G
      pseudotyped retrovirus vectors.
AB  - The inefficient transduction of human hematopoietic stem cells (HSC) with
      amphotropic retroviral vectors has been an obstacle to gene therapy for
      hematopoietic diseases. We have previously reported low levels of amphotropic
      retrovirus receptor (Pit-2) mRNA and higher levels of gibbon ape leukemia virus
      (GALV) or 10A1 retrovirus receptor (Pit-1) mRNA in mouse and human HSC. The
      vesicular stomatitis virus (VSV-G) uses an abundant membrane phospholipid as a
      receptor. We hypothesized that transduction of HSC requires relatively high
      levels of retrovirus receptor molecules. Because mouse HSC can be efficiently
      transduced by ecotropic virus through the abundant ecotropic receptor, the mouse
      is an ideal model to compare receptor levels and transduction. We have developed
      a cotransduction assay where ecotropic retrovirus transduction is a positive
      internal control for downstream steps in retrovirus transduction. A comparison of
      mouse HSC transduction with amphotropic, 10A1, and VSV-G envelopes showed that
      the level of amphotropic and 10A1 receptor mRNA in HSC correlated with the
      frequency of transduction. Transduction with VSV-G vectors was similar to that
      with 10A1 vectors. We conclude that the level of retrovirus receptor on HSC is
      critical for HSC transduction and that GALV or VSV-G vectors would be better for
      human HSC transduction.

PMID- 10933953
TI  - Neural precursor cells for delivery of replication-conditional HSV-1 vectors to
      intracerebral gliomas.
AB  - Cellular delivery of a replication-conditional herpes simplex virus type 1 (HSV
      1) vector provides a means for gene therapy of invasive tumor cells. LacZ-bearing
      neural precursor cells, which can migrate and differentiate in the brain, were
      infected with a ribonucleotide reductase-deficient HSV-1 mutant virus (rRp450)
      that replicates only in dividing cells. Replication of rRp450 in neural precursor
      cells was blocked prior to implantation into the tumor by growth arrest in late
      G1 phase through treatment with mimosine. Viral titers in the medium of mimosine
      treated, rRp450-infected neural precursor cells were below detection levels 3
      days after infection. In culture, after removal of mimosine and passaging, cells
      resumed growth and replication of rRp450 so that, 7 days later, virus was present
      in the medium and cell death was evident. Mimosine-treated neural precursor cells
      injected into established intracerebral CNS-1 gliomas in nude mice migrated
      extensively throughout the tumor and into the surrounding parenchyma beyond the
      tumor over 3 days. Mimosine-treated neural precursor cells, infected with rRp450
      and injected into intracerebral CNS-1 tumors, also migrated within the tumor with
      the appearance of foci of HSV-thymidine kinase-positive (TK+) cells, presumably
      including tumor cells, distributed throughout the tumor and in the surrounding
      parenchyma over a similar period. This migratory cell delivery method has the
      potential to expand the range of delivery of HSV-1 vectors to tumor cells in the
      brain.

PMID- 10933952
TI  - Nuclear-associated plasmid, but not cell-associated plasmid, is correlated with
      transgene expression in cultured mammalian cells.
AB  - Intracellular plasmid is rapidly incorporated into the nucleus of HeLa cells
      following cationic lipoplex transfection. CV1 cells are less effective in
      translocating plasmid to the nucleus and also express less transgene than HeLa
      cells. Cultured HeLa and CV1 cells and corresponding isolated nuclei were
      analyzed after transfection of a Cy3-labeled pGreenLantern plasmid (Cy3-pGL).
      Flow cytometry was used to measure both plasmid delivery and transgene expression
      from the plasmid encoding a CMV promoter-driven green fluorescent protein. During
      transfection, HeLa cells rapidly incorporated the plasmid, reaching a maximum of
      80% Cy3-pGL positive cells 8 h posttransfection. The average Cy3-pGL-positive
      HeLa cell contained approximately 2470 plasmid copies. Forty-eight percent of the
      nuclei isolated from the transfected HeLa cells were positive for the plasmid
      marker after 8 h. In contrast to HeLa cells, fewer CV1 cells and CV1 nuclei
      incorporated plasmid DNA with peak transfection occurring after 12 h for 36% of
      the cells and after 8 h for 12% of the nuclei. However, the average Cy3-pGL
      positive CV1 cell did not have a significantly different number of total cellular
      plasmid copies than the average positive HeLa cell. CV1 nuclei, however, had half
      as much nuclear associated plasmid as HeLa nuclei. HeLa cells are more efficient
      than CV1 cells at transporting plasmid from the cytoplasm to the nucleus. This
      study demonstrates the use of a novel quantitative method to study plasmid
      transport from the cytoplasm to the nucleus and the effect on transgene
      expression.

PMID- 10933954
TI  - Hepatocyte transplantation improves survival in mice with liver toxicity induced
      by hepatic overexpression of Mad1 transcription factor.
AB  - Hepatic overexpression of Mad1 with an adenoviral vector, AdMad, induced liver
      toxicity in immunodeficient mice. Transduction of cultured hepatocytes with AdMad
      inhibited cellular DNA synthesis and cell cycling, along with increased lactate
      dehydrogenase release, indicating cytotoxicity. When dipeptidyl peptidase IV
      deficient F344 rat hepatocytes were transplanted into the liver of
      immunodeficient mice after treatment with AdMad, significant portions of the
      liver were repopulated. This was in agreement with corresponding losses of host
      hepatocytes, which showed increased apoptosis rates. Mortality in mice following
      AdMad treatment decreased significantly when animals were subjected to hepatocyte
      transplantation. The findings indicated that Mad1 overexpression perturbed
      hepatocyte survival. Investigation of pathophysiological mechanisms concerning
      specific cell cycle regulators in acute liver toxicity will thus be appropriate.
      Cell therapy has potential for treating acute liver injury under suitable
      circumstances.

PMID- 10933955
TI  - Optimization of nonviral gene transfer of vascular smooth muscle cells in vitro
      and in vivo.
AB  - Gene therapy strategies for the prevention of restenosis postangioplasty are
      promising. Nonviral gene transfer to the arterial wall in vivo has so far been
      limited by poor efficiency. This study aimed to optimize transfection of primary
      vascular smooth muscle cells using cationic nonviral formulations based on
      cholesterol derivates (DC-, DAC-, DCQ-, and Sp-Chol), double-chained amphiphils
      (LipofectAMINE, DOTMA, DOSGA, DOSPER, and DOCSPER), or heterogeneous reagents
      (Superfect, Effectene, and Tfx-50). Estimation of transfection efficiencies was
      performed using galactosidase assays at different ratios of transfection reagent
      to plasmid DNA with reporter gene. Toxicity was monitored by analyzing cell
      metabolism. Transfer efficiency and safety were determined in a porcine
      restenosis model for local gene therapy using morphometry, histology,
      galactosidase assays, and reverse-transcriptase polymerase chain reaction. The
      highest in vitro transfection efficiency was achieved using the recently
      developed DOCSPER liposomes, with transfer rates of at least 20% in vascular
      smooth muscle cells. Transfer efficiency was further enhanced up to 20% by
      complexing with poly-L-lysine. Transfection efficiency in vivo in a porcine
      restenosis model was up to 15% of adventitial cells using DOCSPER versus 0.1%
      using LipofectAMINE. Toxicity in vivo and in vitro was lowest using DOCSPER.
      Increased biological effects were demonstrated following optimization of transfer
      conditions.

PMID- 10933957
TI  - From the ASGT president

PMID- 10933956
TI  - IRES-dependent second gene expression is significantly lower than cap-dependent
      first gene expression in a bicistronic vector.
AB  - The internal ribosome entry site (IRES) has been widely used to coexpress
      heterologous gene products by a message from a single promoter. However, little
      is known about the efficiency of IRES-dependent second gene expression in
      comparison with that of first gene expression. This study was undertaken to
      characterize the relative expression of IRES-dependent second gene in a
      bicistronic vector, which was derived from the 5' untranslated regions of the
      encephalomyocarditis virus (EMCV). IRES-dependent second gene expression was
      compared with cap-dependent first gene expression in several cultured cell lines
      and in mouse liver in vivo. The expression of the IRES-dependent second gene
      ranged from 6 to 100% (in most cases between 20 and 50%) that of the first gene.
      Second gene expression in a plasmid without the IRES was 0.1-0.8% (with some
      exceptions) that of the first gene. These findings have important implications
      for the use of IRES, i.e., care should be taken regarding the decreased capacity
      of IRES-dependent downstream gene expression as well as in determining which gene
      should be positioned as the first or second gene in a bicistronic vector.

PMID- 10933958
TI  - A prescription for gene therapy.

PMID- 10933959
TI  - AAV and RT-PCR: true or false?

PMID- 10933960
TI  - Genetic targeting of adenoviral vectors.

PMID- 10933961
TI  - Adenovirus-mediated gene therapy for mucopolysaccharidosis VII: involvement of
      cross-correction in wide-spread distribution of the gene products and long-term
      effects of CTLA-4Ig coexpression.
AB  - Recombinant adenoviruses expressing human beta-glucuronidase (AxCAhGUS) and CTLA
      4Ig (AxCACTLA-4Ig) were generated and therapeutic efficacy was investigated using
      a murine model of mucopolysaccharidosis type VII (MPSVII). Seven days after the
      intravenous administration of AxCAhGUS, high levels of beta-glucuronidase (GUSB)
      activity were observed in the liver, spleen, heart, lung, kidney, and serum,
      while viral DNA was predominantly detected in the liver. To investigate the
      contribution of in vivo cross-correction of GUSB between the liver and other
      organs, we injected the serum obtained from the transduced mice into untreated
      MPSVII mice. Similar distributions of GUSB activity were observed in the serum
      injected mice, suggesting that GUSB activities detected in the extrahepatic
      organs were due to the cross-correction rather than the direct gene transduction.
      This result also suggested that maintaining high levels of GUSB in the systemic
      circulation was essential for the effective treatment of MPSVII. To achieve this,
      we injected AxCAhGUS and AxCACTLA-4Ig into MPSVII mice. Serum GUSB activity was
      sustained at high levels for more than 200 days and morphological normalization
      of the liver and spleen was observed for a year. This suggests that long-term
      therapeutic efficacy in visceral organs of MPSVII is achievable by coexpression
      of CTLA-4Ig through an in vivo cross-correction pathway.

PMID- 10933962
TI  - In vivo selection of hepatocytes transduced with adeno-associated viral vectors.
AB  - A murine model for hereditary tyrosinemia Type I (HTI) was evaluated for in vivo
      gene therapy with adeno-associated viral (AAV) vectors expressing the enzyme
      fumarylacetoacetate hydrolase. Transduction of a limited number of hepatocytes
      was accomplished following infusion of vector into the portal circulation.
      Corrected hepatocytes were expanded in vivo by withdrawing a drug which prevents
      the accumulation of toxic metabolites. The liver was eventually repopulated with
      hepatocytes harboring a functional and apparently integrated AAV provirus.
      Recipient animals regained normal liver function and architecture and the
      underlying metabolic derangements were normalized. After 9 months, vector-treated
      animals showed benign hepatomas, whereas in untreated animals areas of marked
      dysplasia were present within hepatomas.

PMID- 10933963
TI  - Biocompatibility of cardiovascular gene delivery catheters with adenovirus
      vectors: an important determinant of the efficiency of cardiovascular gene
      transfer.
AB  - Gene therapy approaches hold promise for the treatment of a wide variety of
      cardiovascular diseases. Many strategies for cardiovascular gene therapy involve
      catheter-mediated vector delivery via intramyocardial injection, intracoronary
      infusion, or direct gene transfer into the vessel wall. Several different gene
      delivery catheters have been developed and utilized in preclinical and clinical
      studies of cardiovascular gene therapy. However, rigorous studies of the
      biocompatibility of these catheters with gene therapy vectors have not yet been
      reported. In this report, we have examined the compatibility of cardiovascular
      gene therapy catheters and catheter constituents with first-generation E1/E3
      deleted adenovirus vectors. We show that (i) currently available catheters
      rapidly and efficiently inactivate adenovirus vector infectivity; (ii) this
      inactivation is mediated by a variety of commonly used catheter constituents
      including stainless steel, nitinol, and polycarbonate; (iii) catheter-mediated
      inactivation of adenovirus vectors can be prevented by preflushing catheters with
      solutions of serum albumin; and (iv) it is possible to identify a set of catheter
      materials that are compatible with current adenovirus vectors. These results
      underscore the importance of catheter/vector compatibility and suggest methods
      for increasing the efficiency of catheter-mediated cardiovascular gene therapy.

PMID- 10933965
TI  - Retroviral delivery of peptide modulators of cellular functions.
AB  - Stable transduction of genetic material, in combination with sensitive
      methodologies for in vivo study of cell physiology, provides an opportunity to
      efficiently evaluate the functions of regulatory proteins. To dissect the minimal
      therapeutic function of such proteins, we have stably expressed protein
      microdomains as fusions, composed of short peptides, and detected specific
      subfunctions distinct from holoprotein function, using flow cytometry and other
      techniques. We demonstrate that retroviral delivery of the 24-amino-acid
      proliferating cell nuclear antigen-binding motif (p21C), derived from the C
      terminus of the cell cycle inhibitor protein, p21, is sufficient to induce cell
      cycle arrest. Cells expressing this peptide motif reversibly execute both G1- and
      G2-checkpoint controls that are normally activated subsequent to interference
      with DNA synthesis. The p21C effect is distinct from results obtained with an
      intact p21 protein that also binds cyclin-CDK complexes and arrested cells
      exclusively at the G1/S transition. Thus, microdomains can exert unique
      biological effects compared to the parental molecules from which they were
      derived. To further evaluate the peptide delivery strategy, we analyzed the role
      of various kinases in IgE-mediated stimulation of mast cell exocytosis. Primary
      bone marrow-derived mast cells were transduced with retroviral constructs
      encoding short-kinase inhibitor motifs and analyzed by flow cytometry for effects
      on exocytosis. We found that a specific protein kinase A (PKA) inhibitor peptide
      suppressed IgE-mediated stimulation of mast cell exocytosis. This anti-exocytotic
      effect was mimicked by a small molecule inhibitor of PKA (KT5720). Thus, the
      ability to express protein microdomains can be a powerful means to subtly perturb
      cellular physiology in manners that reveal new paths for therapeutic
      intervention. We believe that such approaches might allow for new forms of gene
      therapy to become available.

PMID- 10933966
TI  - CD34 splice variant: an attractive marker for selection of gene-modified cells.
AB  - This study presents a promising selection system for gene-modified cells other
      than human hematopoietic progenitor and endothelial cells based on transgenic
      expression of human CD34. Three retrovirally transduced variants of CD34 were
      compared, differing in the length of their cytoplasmic domains. These were the
      full-length transmembrane protein (flCD34), a truncated form (tCD34) that is
      found as a naturally occurring splice variant and has a partial deletion of the
      cytoplasmic domain for signal transduction, and an engineered variant which is
      completely deprived of its cytoplasmic tail (dCD34). All three variants allowed
      selection of gene-modified cells using commercially available immunoaffinity
      technology. However, examination by flow cytometry as well as by Southern,
      Northern, and Western blot revealed that dCD34, as opposed to tCD34, is not
      stably anchored in the membrane and thus is expressed at low levels on the
      surface of transduced cells. Therefore, tCD34 was chosen as the more promising
      candidate for a clinically applicable cell surface marker. We show that gene
      modified human primary T lymphocytes expressing tCD34 can be enriched to high
      purity (>95%) using clinically approved immunoaffinity columns. In addition, we
      demonstrate the utility of tCD34 for surface marking of murine hematopoietic
      cells in vivo, including primary T lymphocytes detected 9 weeks after bone marrow
      transplantation.

PMID- 10933964
TI  - Prolongation of cardiac allograft survival using dendritic cells treated with NF
      kB decoy oligodeoxyribonucleotides.
AB  - Dendritic cells (DC) classically promote immune responses but can be manipulated
      to induce antigen-specific hyporesponsiveness in vitro. The expression of
      costimulatory molecules (CD40, CD86, CD80) at the DC cell surface correlates with
      their capacity to induce or suppress immune responses. Expression of these
      molecules is associated with NF-kB-dependent transcription of their genes. DC
      tolerogenicity has been associated with impaired NF-kB-dependent transcription of
      costimulatory genes as well as NF-kB translocation to the nucleus. In this
      report, we demonstrate that double-stranded oligodeoxyribonucleotides containing
      binding sites for NF-kB (NF-kB ODN) are efficiently incorporated by bone marrow
      derived DC and specifically inhibit NF-kB-dependent transcription of a reporter
      gene. Moreover, exposure of DC to the oligonucleotide decoys inhibited
      lipopolysaccharide (LPS)-induced nitric oxide production, a marker of DC
      maturation. Treatment of bone marrow-derived DC progenitors with NF-kB ODN
      selectively suppressed the cell-surface expression of costimulatory molecules
      without interfering with MHC class I or class II expression. Furthermore, NF-kB
      ODN DC induced allogeneic donor-specific hyporesponsiveness in mixed leukocyte
      cultures, and this was associated with inhibition of Th1-type cytokine
      production. Finally, infusion of NF-kB ODN-modified bone marrow-derived DC into
      allogeneic recipients prior to heart transplantation resulted in significant
      prolongation of allograft survival in the absence of immunosuppression. Specific
      interference with NF-kB and other transcriptional pathways involved in immune
      stimulation in DC using ODN decoy approaches could be one means to promote
      tolerance induction in organ transplantation.

PMID- 10933967
TI  - Use of the ornithine decarboxylase promoter to achieve N-MYC-mediated
      overexpression of a rabbit carboxylesterase to sensitize neuroblastoma cells to
      CPT-11.
AB  - Overexpression of specific transcription factors by tumor cells can be exploited
      to regulate expression of proteins that induce apoptosis or activate prodrugs,
      thereby producing tumor-selective toxicity. A majority of advanced-stage
      neuroblastomas overexpress the transcription factor N-MYC, and this
      overexpression is associated with poor prognosis. This study describes regulation
      of expression by N-MYC, via the ornithine decarboxylase (ODC) promoter, of a
      rabbit liver carboxylesterase (CE) that activates the prodrug CPT-11.
      Chloramphenicol acetyltransferase reporter assays and CE activity assays in
      transiently transfected neuroblastoma cell lines (SJNB-1, SJNB-4, NB-1691) and
      rhabdomyosarcoma cell lines (JR1neo20, JR1Nmyc6, JR1Nmyc9) support this approach
      as a potential method for sensitizing tumor cells to CPT-11. Clonogenic assays
      with IMR32 human neuroblastoma cells which express N-MYC and that had been stably
      transfected with a plasmid containing an ODC promoter/CE cassette corroborated
      results of enzyme activity assays. Specifically, IMR32.ODC.CE cells expressed
      approximately eightfold more CE activity than IMR32.CMV.neo cells; and 5 microM
      CPT-11 reduced the clonogenic potential of IMR32.ODC.CE cells to zero, while 50
      microM CPT-11 was required to produce the same effect with IMR32.CMV.neo cells.
      Current experiments focus on adenoviral delivery of an ODC promoter/CE cDNA
      cassette for potential virus-directed enzyme prodrug therapy applications.

PMID- 10933968
TI  - Herpes simplex viral and amplicon vector-mediated gene transfer into glia and
      neurons in organotypic spinal cord and dorsal root ganglion cultures.
AB  - The progression of neurodegenerative diseases and secondary consequences of
      spinal cord injury may be diminished by introducing transgenes to glia, spinal
      neurons, and/or sensory neurons. Organotypic cultures of spinal cord slices and
      dorsal root ganglia proved to be an excellent system in which to compare the
      relative neurotropism of a replication-defective recombinant herpes simplex virus
      and herpes virus-derived amplicon vectors. Hundreds of beta-galactosidase
      expressing cells, transduced by the viral vectors, were observed in spinal cord
      slices 3 and 8 days postinfection. Immunostaining to identify the infected cell
      type indicated that oligodendrocytes were permissive for viral vector
      transduction of beta-galactosidase in the spinal cord slice, whereas neurons were
      not. Heparan sulfate proteoglycan, the initial receptor for herpes contact with
      cells, was highly expressed in the white matter of the spinal cord slice, but was
      negligible in the gray matter. In contrast to the spinal cord, many fewer cells
      were infected in the dorsal root ganglia (DRG) by these vectors, but a majority
      of infected cells were identified as sensory neurons. Heparan sulfate
      proteoglycan expression was abundant in the sensory fibers emanating from the DRG
      and also surrounded each neuron within the ganglion. Our results demonstrate HSV
      induced transgene expression that is amenable to ex vivo assessment of its
      physiological impact.

PMID- 10933969
TI  - A modular set of helper-dependent herpes simplex virus expression vectors.
AB  - Herpes simplex virus (HSV) has many favorable properties in terms of its
      potential to serve as a delivery and expression platform for gene-based
      therapies, including the ability to establish persistent infections, a broad
      tissue tropism, episomal maintenance of transduced genes, and a large genome that
      can incorporate many additional cDNAs. Helper-dependent HSV vectors (commonly
      known as HSV amplicons) are well positioned to exploit the biology of the virus,
      since they contain only the two cis elements required for HSV replication and
      packaging and thus do not require the silencing of any viral genes to prevent
      toxicity to transduced cells over the course of cDNA expression. In this report
      we describe the development of a set of modular HSV amplicon vectors that can
      easily be modified to incorporate different genetic elements or alternatively can
      be used to retrofit existing expression constructs such that they can be packaged
      into infectious HSV particles.

PMID- 10933970
TI  - Characterization of the dopamine defect in primary cultures of dopaminergic
      neurons from hypoxanthine phosphoribosyltransferase knockout mice.
AB  - Lesch-Nyhan disease (LND) is an X-linked metabolic disorder caused by lack of
      activity of the purine salvage enzyme hypoxanthine phosphoribosyltransferase
      (HPRT) and characterized by hyperuricemia and debilitating neurological
      manifestations. The mechanisms underlying the neuropathology are not well
      understood and the principal neurochemical lesion characterized to date is a
      deficiency of the dopamine system in the basal ganglia. To facilitate the study
      of mechanism(s) by which HPRT deficiency causes the dopamine defect, we have
      compared the survival and dopamine phenotype of primary cultures of dopamine
      neurons derived from HPRT-deficient mice with the dopaminergic neurons from wild
      type mice. The survival of dopaminergic neurons from both sources was promoted to
      an equal extent by glial cell line-derived neurotrophic factor (GDNF), a potent
      survival factor for dopamine neurons in vitro. Although the survival of the HPRT
      deficient neurons was indistinguishable from that of cells derived from wild-type
      counterparts, the HPRT-deficient cells demonstrated a persistent deficiency of
      dopamine content and dopamine uptake with increasing neuritic differentiation,
      indicating that GDNF does not restore the normal phenotype in HPRT-deficient
      dopamine neurons despite its well-known protective and regenerative properties in
      several neurodegeneration models. Nevertheless, the demonstration that GDNF
      trophic support promotes the survival of these dopaminergic neurons will
      facilitate gaining a better understanding of the neuropathological mechanisms of
      LND by allowing a more extensive analysis of the cells central to the Lesch-Nyhan
      phenotype, the dopaminergic neurons of the basal ganglia.

PMID- 10933971
TI  - Gene therapy: beyond 2000.

PMID- 10933972
TI  - Parkinson's disease: a neurodegenerative disease particularly amenable to gene
      therapy.

PMID- 10933974
TI  - Gene therapy for ocular disease.

PMID- 10933973
TI  - Gene-based vaccines.

PMID- 10933975
TI  - Adeno-associated viral-mediated gene transfer to hepatoma: thymidine
      kinase/interleukin 2 is more effective in tumor killing in non-ganciclovir (GCV)
      treated than in GCV-treated animals.
AB  - Interleukin 2 (IL-2) enhancement of herpes simplex virus-thymidine kinase (HSV
      TK)/ganciclovir (GCV)-induced tumor killing was studied by cloning the human
      interleukin 2 gene into an HSV-TK-bearing adeno-associated viral (AAV) vector
      (TK/IL-2). The mouse hepatocellular carcinoma cell line Hepa 1-6 was used as a
      model in this study. We found that TK/IL-2-transduced Hepa 1-6 cells were more
      susceptible to ganciclovir treatment than tumor cells transduced with only TK in
      both nude mice and immunocompetent C57L/J mice. TK/IL-2-transduced tumors also
      showed shrinkage without GCV treatment. The tumor-killing effect of AAV-mediated
      TK/IL-2 gene transfer was further studied by inoculating animals with TK/IL-2- or
      TK-transduced tumor cells mixed with unmodified cells with or without GCV
      treatment. Although tumor growth in each group was inhibited, the best result was
      obtained from the TK/IL-2-transduced group without GCV treatment. In this group,
      10% of the transduced tumor cells could eradicate the whole tumor in 50% of the
      animals tested as well as provide long-term protection against tumor cell
      rechallenge. When this group was treated with GCV, the antitumor effect of TK/IL
      2 was reduced. We attribute this to the early ablation of transgene-bearing tumor
      cells by GCV treatment, which thus reduces the duration of IL-2 expression. We
      conclude that (i) TK/IL-2 plus GCV treatment generates a stronger tumor-killing
      effect than HSV-TK plus GCV and (ii) tumor killing of TK/IL-2 is more effective
      in non-GCV-treated animals than in GCV-treated animals.

PMID- 10933976
TI  - Lentiviral vectors: regulated gene expression.
AB  - Lentiviral vectors can deliver and express genes in a wide variety of dividing
      and nondividing cells. These include terminally differentiated neurons, myotubes,
      hepatocytes, and hematopoietic stem cells. We now describe the generation of
      lentiviral vectors in which the expression of the transgene can be regulated. We
      have developed an inducible lentiviral vector system that contains the entire
      tetracycline (Tet)-regulated system developed by H. Bujard and colleagues. The
      novel vector expresses the GFP reporter gene and the tetracycline transactivator
      under the control of the tetracycline-inducible promoter and the human CMV
      promoter, respectively. In vitro transduction of human 293 cells resulted in a
      very low basal expression of GFP in the presence of the effector substance
      doxycyline. Withdrawal of doxycyline induced a more than 500-fold increase in
      transgene expression. Switching transgene expression "off and on" did not change
      either the kinetics or the magnitude of induction. Maximal suppression of GFP
      mRNA transcription was achieved within 24 h of addition of the drug; however, due
      to the slow turnover rate of GFP, green fluorescent cells could be detected up to
      10 days following doxycyline treatment. Following transduction of rat brain with
      recombinant lentiviruses, doxycyline-regulated GFP expression could be observed
      in terminally differentiated neurons. Specifically, by adding or withdrawing
      doxycyline from the rats' drinking water, induction and suppression of GFP
      expression could be regulated in vivo. These studies show that an inducible
      lentiviral vector can deliver and regulate transgene expression in vivo. We
      believe that regulated gene expression is an essential tool for successful gene
      therapy approaches.

PMID- 10933977
TI  - Inclusion of the hepatic locus control region, an intron, and untranslated region
      increases and stabilizes hepatic factor IX gene expression in vivo but not in
      vitro.
AB  - We systematically compared human factor IX gene expression from a variety of
      plasmids containing different cis-regulatory sequences after transfection into
      different hepatocyte cell lines, or in vivo, after their injection into the
      livers of mice. Although there was a 1.5- to 2.0-fold variation in gene
      expression from cultured cells, a 65-fold variation was observed in the in vivo
      studies. We found that a plasmid containing the apolipoprotein E locus control
      region (HCR), human alpha1-antitrypsin (hAAT) promoter, hFIX minigene (hFIXmg)
      sequence including a portion of the first intron (intron A), 3'-untranslated
      region (3'-UTR), and a bovine growth hormone polyadenylation signal (bpA)
      produced the highest serum level of human factor IX, reaching 18 microg/ml
      (normal = 5 microg/ml) 1 day after injection. Although most of the plasmid DNAs
      resulted in transient gene expression, inclusion of an intron, a polyadenylation
      signal from either the 1.7-kb 3'-UTR or the 0.3-kb bpA, and the HCR resulted in
      persistent and therapeutic levels of hFIX gene expression, ranging from 0.5 to 2
      microg/ml (10 to 40% of normal) for 225 days (length of experiment). These data
      underscore the importance of cis sequences for enhancing in vivo hepatic gene
      expression and reemphasize the lack of correlation of gene expression in tissue
      culture and in vivo studies.

PMID- 10933978
TI  - Introduction of a xenogeneic gene via hematopoietic stem cells leads to specific
      tolerance in a rhesus monkey model.
AB  - Host immune responses against foreign transgenes may be a major obstacle to
      successful gene therapy. To clarify the impact of an immune response to foreign
      transgene products on the survival of genetically modified cells, we studied the
      in vivo persistence of cells transduced with a vector expressing a foreign
      transgene compared to cells transduced with a nonexpressing vector in the
      clinically predictive rhesus macaque model. We constructed retroviral vectors
      containing the neomycin phosphotransferase gene (neo) sequences modified to
      prevent protein expression (nonexpressing vectors). Rhesus monkey lymphocytes or
      hematopoietic stem cells (HSCs) were transduced with nonexpressing and neo
      expressing vectors followed by reinfusion, and their in vivo persistence was
      studied. While lymphocytes transduced with a nonexpressing vector could be
      detected for more than 1 year, lymphocytes transduced with a neo-expressing
      vector were no longer detectable within several weeks of infusion. However, five
      of six animals transplanted with HSCs transduced with nonexpression or neo
      expression vectors, and progeny lymphocytes marked with either vector persisted
      for more than 2 years. Furthermore, in recipients of transduced HSCs, infusion of
      mature lymphocytes transduced with a second neo-expressing vector did not result
      in elimination of the transduced lymphocytes. Our data show that introduction of
      a xenogeneic gene via HSCs induces tolerance to the foreign gene products. HSC
      gene therapy is therefore suitable for clinical applications where long-term
      expression of a therapeutic or foreign gene is required.

PMID- 10933979
TI  - An adenovirus encoding proapoptotic Bax induces apoptosis and enhances the
      radiation effect in human ovarian cancer.
AB  - Overexpression of proapoptotic Bax favors death in cells resistant to ionizing
      radiation. We hypothesized that expression of Bax via adenoviral-mediated gene
      delivery could sensitize radiation-refractory cells to radiotherapy. An inducible
      Bax recombinant adenovirus (Ad/Bax) had been generated using the Cre/loxp system.
      Human ovarian cancer cell lines and primary, patient-derived cancer cells from
      ascites were irradiated and infected with the Ad/Bax and an expression-inducing
      vector, Ad/Cre. Cell death was evaluated by crystal violet staining, fluorescence
      activated cell sorter analysis of Annexin V, and colony formation assay (cell
      lines only). To further characterize the mechanism of death, cell morphology was
      examined by nuclear staining with Hoechst 33258. Lastly, to evaluate the capacity
      of the combined treatment to inhibit tumor growth, mice were injected
      subcutaneously with ovarian cancer cells exposed to Bax, radiation therapy (RT),
      or both, and tumor size was measured periodically. Infection of the cancer cell
      lines and primary cells with both Ad/Bax and Ad/Cre significantly enhanced
      sensitivity to ionizing radiation, achieving high levels of cell killing in short
      term assays. In addition, the combination of Bax and radiotherapy reduced the
      survival fraction of cell lines 2 logs in standard colony-forming assays.
      Investigation into the involved mechanism suggests that Bax-mediated
      radiosensitization occurs through both apoptosis and necrosis pathways. Further,
      mice subcutaneously injected with ovarian tumor cells previously treated with
      radiation, or with radiation and irrelevant viruses, consistently developed tumor
      nodules. In addition, approximately 80% of injections were followed by tumor
      formation after treatment with Ad/Bax and Ad/Cre alone. In contrast, tumor
      formation was completely inhibited after combined treatment with Ad/Bax and
      Ad/Cre and radiation. Augmentation of the effect of radiotherapy on human ovarian
      cancer cells and primary cancer cells from patients via a recombinant adenovirus
      encoding Bax is feasible.

PMID- 10933980
TI  - Restricted expression of an adenoviral vector encoding Fas ligand (CD95L)
      enhances safety for cancer gene therapy.
AB  - Gene transfer of Fas ligand (CD95L) using adenoviral vectors has been shown to
      generate apoptotic responses and potent inflammatory reactions that can be used
      to induce the regression of malignancies in vivo, but these vectors also cause
      significant hepatotoxicity that may limit their clinical utility. Here we
      describe an adenoviral vector encoding CD95L with restricted gene expression that
      reduces its toxicity in vivo. Preclinical efficacy and gene expression studies of
      lineage-restricted CD95L adenoviral vectors were performed. To enhance its
      cytotoxicity and reduce potential systemic effects, a noncleavable CD95L was made
      by deleting a segment containing the cleavage site (CD95L deltaQP). Higher CD95L
      expression of this mutant was observed on the tumor cell surface, together with a
      reduction in the release of soluble CD95L. This CD95L cleavage mutant was then
      expressed under control of a smooth muscle-specific promoter, SM22apha, and
      analyzed for its ability to suppress the growth of tumors of smooth muscle origin
      in vivo. Growth of human leiomyosarcomas but not gliomas was inhibited after ADV
      gene transfer into tumor-bearing immunodeficient mice. In contrast to viral
      promoters, in which mortality was uniformly seen after injection of 10(12)
      particles, no significant hepatic injury or systemic toxicity was observed in
      mice, and the maximum tolerated dose was increased > or = 10- to 100-fold. These
      findings suggest that restricted specificity of adenoviral CD95L gene expression
      enhances the safety of this approach for cancer gene therapy.

PMID- 10933981
TI  - Transduction of human CD34+ CD38- bone marrow and cord blood-derived SCID
      repopulating cells with third-generation lentiviral vectors.
AB  - The major limitations of Moloney murine leukemia virus (MoMLV)-based vectors for
      human stem cell applications, particularly those requiring bone marrow (BM) stem
      cells, include their requirement for mitosis and retroviral receptor expression.
      New vectors based upon lentiviruses such as HIV-1 exhibit properties that may
      circumvent these problems. We report that novel third-generation, self
      inactivating lentiviral vectors, expressing enhanced green fluorescent protein
      (EGFP) and pseudotyped with vesicular stomatitis virus G glycoprotein (VSV-G),
      can efficiently transduce primitive human repopulating cells derived from human
      BM and cord blood (CB) tested by the SCID-repopulating cell (SRC) assay. Highly
      purified CD34+ CD38- CB or BM cells were efficiently transduced (4-69%) and
      stably expressed in EGFP for 40 days in culture following infection for only 24 h
      without fibronectin, polybrene, or cytokines. Nonobese diabetic/severe combined
      immune-deficient (NOD/SCID) mice transplanted with transduced cells from either
      CB or BM donors were well engrafted, demonstrating maintenance of SRC during the
      infection procedure. Serially obtained femoral BM samples indicated that the
      proportion of EGFP+ cells within both myeloid and lymphoid lineages was
      maintained or even increased over time, averaging 42.3 +/- 6.6% for BM donors and
      23.3 +/- 7.2% for CB at 12 weeks. Thus, the third-generation lentivectors readily
      transduce human CB and BM stem cells, under minimal conditions of ex vivo
      culture, where MoMLV-based vectors are ineffective. Since CB is inappropriate for
      most therapeutic applications, the efficient maintenance and transduction of BM
      derived SRC during the short infection procedure are notable advantages of
      lentivectors.

PMID- 10933982
TI  - Amplification of transgene expression in vitro and in vivo using a novel
      inhibitor of histone deacetylase.
AB  - Enhancement of transgene expression is an important issue in human gene therapy.
      Here we describe a novel system for enhancing transgene expression by
      cointroduction of plasmid DNA with FR901228, a water-soluble histone deacetylase
      inhibitor. When a luciferase expression vector was cointroduced into cells with
      FR901228, luciferase gene expression was enhanced 50-fold in the mouse melanoma
      cell line B16-F1 and 5200-fold in NIH3T3 cells in comparison to cells without the
      drug. Luciferase gene expression enhancement was dependent on both drug dose and
      treatment time. Acetylated histones increased in accordance with drug dose, and
      the activation of gene expression occurred at the transcriptional level. The
      stimulation of luciferase gene expression by FR901228 was also observed in a B16
      F1 clone stably expressing luciferase. Cointroduction of the luciferase plasmid
      with FR901228 into a B16-F1 tumor mass activated luciferase gene expression 3- to
      4-fold. Thus, activation of transgene expression by FR901228 may serve as a new
      tool for gene therapy.

PMID- 10933983
TI  - Conflict of interest.

PMID- 10933984
TI  - A population-based study of the prevalence, clinical characteristics and effect
      of ethnicity in epilepsy.
AB  - The aim of this study was to determine the prevalence and clinical
      characteristics of epilepsy and seizure disorders in Bradford. The method used
      was a community-based cross-sectional study. Case ascertainment was by review of
      medical records identified by searching practice databases using diagnostic codes
      and from repeat prescribing data. A specialist epilepsy nurse reviewed the
      records in 39 practices covering a population of 225 439. Clinical review was
      undertaken where there was limited information available in the records. In
      total, 1643 cases of epilepsy were identified (prevalence 7.3/1000). The
      prevalence of epilepsy increased with age. Classification of patients by
      internationally agreed definitions showed 1013 (62%) of cases with active
      epilepsy (prevalence 4. 5/1000); 421 (26%) with epilepsy in remission on
      treatment and 209 (13%) with epilepsy in remission off treatment. The
      standardized rate for all patients of South Asian origin was 3.6/1000 compared to
      7.8/1000 in the rest of the population (OR 0.46; 95% CI 0.38, 0.57). An
      underlying aetiology was identified in 29.5% of cases. Cerebrovascular disease
      and head injuries were the commonest causes. CONCLUSIONS: The prevalence of
      epilepsy supports previous epidemiological estimates and highlights the public
      health importance of epilepsy. The low prevalence in the South Asian population
      is a surprising finding and further research into cultural attitudes to epilepsy
      and the impact of stigma in the South Asian population in the UK is required.

PMID- 10933985
TI  - Dissociation, hypnotizability, coping styles and health locus of control:
      characteristics of pseudoseizure patients.
AB  - Although literature in this area is relatively sparse, the occurrence of
      psychogenic non-epileptic seizures (pseudoseizures) has been linked to stress,
      anxiety and possible dissociative tendencies. An association between dissociation
      and hypnotic susceptibility has also been proposed and dissociative tendencies
      have themselves been found to relate to the use of emotion-focused coping
      strategies. In order to investigate the hypothesis that pseudoseizure patients
      may exhibit higher levels of dissociation, a more emotion-focused coping style,
      and greater hypnotic susceptibility than the general population, the
      questionnaire responses of 20 patients with pseudoseizures were compared with
      those obtained from a non-clinical control group. As predicted, pseudoseizure
      patients demonstrated some evidence of higher levels of dissociation and escape
      avoidance coping strategies. They also expressed a greater belief in external
      control over health and higher depression scores, compared to the control group,
      but the previously reported elevation in hypnotizability scores in the
      pseudoseizure patients was not found. Possible explanations for this pattern of
      results are discussed.

PMID- 10933986
TI  - Near infrared spectroscopy (NIRS) distinguishes seizure types.
AB  - Near infrared spectroscopy (NIRS) is a noninvasive method for bedside measurement
      of cerebral oxygenation (SaO(2)). The purpose of this study was to establish
      differences in SaO(2)for complex partial seizures (CPS) and rapidly secondarily
      generalized CPS (RCPS). We studied eight adults with medically refractory
      epilepsy undergoing evaluation for temporal lobectomy. We continually measured
      cerebral SaO(2)via a Somanetic Invos 3100a cerebral oximeter, pre-ictal (5
      minutes), ictal, immediate (30 seconds) post-ictal, and late post-ictal (5
      minutes after ictus). Seventeen seizures (12 CPS, four RCPS and one subclinical)
      were recorded in eight patients. The percentage change in cerebral SaO(2)from pre
      ictal to ictal periods was derived. Cerebral SaO(2)increased (percentage change,
      mean: 16.6, SD: 13.9) for CPS and decreased (percentage change, mean: 51.1, SD:
      18.1) for RCPS. No change in cerebral oximetry was recorded for the subclinical
      seizure. Post-ictal (immediate and late) increase in cerebral SaO(2)was seen for
      11 of the 17 seizures (nine CPS and two RCPS). Peripheral SaO(2)rose greater than
      93% for all CPS and the subclinical seizure, but decreased between 78 and 84%
      during RCPS. These results suggest NIRS distinguishes cerebral SaO(2)patterns
      between CPS and RCPS. The decrease in peripheral SaO(2), however, may account for
      the decrease in cerebral SaO(2)seen in generalized seizures.

PMID- 10933987
TI  - Inter-ictal and post-ictal psychoses in frontal lobe epilepsy: a retrospective
      comparison with psychoses in temporal lobe epilepsy.
AB  - There have been few studies of the psychopathology of patients with frontal lobe
      epilepsy (FLE). The majority of studies of both inter-ictal and post-ictal
      psychoses have strongly suggested the influence of temporal lobe disturbance on
      psychoses. Patients with organic brain damage or schizophrenia, however,
      sometimes show frontal lobe dysfunction. The purpose of this study was to better
      understand the effect, if any, of frontal lobe disturbance and seizure on
      psychopathology. Patients were divided into four groups based on epilepsy type
      and preceding seizures; 8 with FLE/inter-ictal psychosis, 3 with FLE/post-ictal
      psychosis, 29 with temporal lobe epilepsy (TLE)/inter-ictal psychosis, and 8 with
      TLE/post-ictal psychosis. Psychopathologic symptoms were retrospectively reviewed
      based on case notes, using a modified brief psychiatric rating scale (BPRS).
      Psychomotor excitement, hostility, suspiciousness, and hallucinatory behaviour
      were prominent features in all four groups. Six orthogonal factors were derived
      by factor analysis from the original data based on the 18 BPRS items. FLE
      patients with inter-ictal psychosis showed marked hebephrenic characteristics
      (i.e. emotional withdrawal and blunted effect). Our findings suggest that
      patients with FLE can exhibit various psychiatric symptoms. However, their
      psychotic symptoms, hebephrenic symptoms in particular, may often be overlooked.

PMID- 10933988
TI  - The lateralizing and surgical prognostic value of a single 2-hour EEG in mesial
      TLE.
AB  - We investigated 109 patients who received anterior temporal lobectomy for
      intractable mTLE by post-operative follow-up for at least 11/2 years. We reviewed
      pre-operative 2-hour interictal EEGs, counted interictal epileptiform discharges
      (IEDs), and compared the lateralization of IEDs with the side of surgery and
      surgical outcome. Twenty of 22 patients who had no spikes and 44 of 51 who had
      unitemporal spikes became seizure free after surgical resection. The correct
      lateralization of the epileptogenic side was possible in 90. 9% of the patients
      with unitemporal IEDs. In 12 seizure-free patients of 15 patients with less than
      70% predominance of IED in one temporal lobe, the positive predictive value of
      the lateralization was 41.7%. In 16 seizure-free patients of 21 with more than
      70% preponderance of IED in one lobe, the positive predictive value was 81.3%.
      Surgical outcome of patients with unitemporal and bitemporal IEDs were not
      significantly different. Interictal scalp EEG can be used as a lateralizing tool
      in mTLE when the temporal IEDs appear with more than 70% preponderance in one
      side. Although the presence of bitemporal IEDs often causes confusion in terms of
      the correct lateralization, it does not affect the surgical outcome.

PMID- 10933989
TI  - The information needs and understanding of 5-10-year old children with epilepsy,
      asthma or diabetes.
AB  - This exploratory study compared the information needs and understanding of 25 5
      10-year olds with epilepsy with those of 10 children with asthma and 10 with
      diabetes (of the same age range). The children were interviewed whilst attending
      specialist clinics by the first author and were unaware of her professional
      status. All the children had access to specialist nurses and their families had
      received literature about their condition. The interview covered five main areas:
      knowledge of their condition, psychological effects, medication, restrictions on
      lifestyle, where they obtained their information and if they had unanswered
      questions. The children with epilepsy had far more unanswered questions and felt
      excluded from discussions with doctors. They also appeared reluctant to tell
      their friends their diagnosis and, at such a young age, felt stigmatized by their
      condition. The results highlight a contrast in the understanding of children with
      epilepsy when compared with those with asthma or diabetes. It is proposed that if
      a simple biological model were used to explain epilepsy this could aid children's
      understanding and reduce their reluctance to disclose their diagnosis.

PMID- 10933990
TI  - Familial adult onset myoclonic epilepsy associated with migraine.
AB  - We report a new type of migraine associated epileptic syndrome in a family: adult
      onset myoclonic epilepsy with benign course and migraine. Affected members of the
      family had myoclonic and rare generalised tonic-clonic seizures. Most of the
      patients, but not all, had a history of migraine. Also, some cases of the family
      had only migraine. This family will be discussed because of two distinct
      features. Firstly, in this family a different type of epilepsy, adult onset
      myoclonic epilepsy was diagnosed that has not been classified in the ILAE 1989,
      classification(s), but was similar to that previously reported in Japanese
      families. Secondly, in most of the cases migraine was associated with the
      epilepsy.

PMID- 10933991
TI  - The relationship between photosensitive temporal lobe epilepsy and eye closure
      activity.
AB  - We describe a 16-year-old female patient affected by photo-induced temporal lobe
      epilepsy. During intermittent photic stimulation she showed a photoparoxysmal
      response in the EEG. This case was diagnosed from clinical symptoms, single
      photon emission computer tomography, and EEG data. The clinical symptoms were
      relieved by the administration of carbamazepine. As these photoparoxysmal
      responses were observed not only during photic stimulation, but also when patient
      was closing her eyes during an eye-opening test in complete darkness, we propose
      the existence of an alternative pathway such as from the extraocular muscles or
      orbicularis oculi, or activation of cortical activity due to the change of
      consciousness by closing eyes in inducing photosensitive epilepsy. We describe an
      additional case and discuss a novel aspect of photo-induced temporal lobe
      epilepsy.

PMID- 10933992
TI  - A case of post-anoxic encephalopathy with initial massive myoclonic status
      followed by alternating Jacksonian seizures.
AB  - To contrast stimulus-sensitive generalized myoclonus with ensuing multifocal
      localized myoclonus in a patient with post-anoxic coma, we stressed the clinical
      as well as electroencephalographical differences between his initial generalized
      and subsequent focal myoclonus. While generalized myoclonus was presumably of
      extracortical origin and responsive to valproic acid, alternating Jacksonian
      seizures were definitely cortical and suppressed with phenytoin. These two
      different types of myoclonus should not be confused in post-anoxic coma.

PMID- 10933993
TI  - Abstracts of posters presented at 'Northern Exposure' annual scientific meeting
      of the British Branch of the International League against Epilepsy, Edinburgh,
      March 30th-April 1st, 2000.

PMID- 10933994
TI  - Re: Shorvon 'Oxcarbazepine, a review' Seizure 2000;9:75-79.

PMID- 10933997
TI  - Sensory habituation of auditory receptor neurons: implications for sound
      localization.
AB  - Auditory receptor neurons exhibit sensory habituation; their responses decline
      with repeated stimulation. We studied the effects of sensory habituation on the
      neural encoding of sound localization cues using crickets as a model system. In
      crickets, Teleogryllus oceanicus, sound localization is based on binaural
      comparison of stimulus intensity. There are two potential codes at the receptor
      neuron level for interaural intensity difference: interaural difference in
      response strength, i.e. spike rate and/or count, and interaural difference in
      response latency. These are affected differently by sensory habituation. When
      crickets are stimulated with cricket-song-like trains of sound pulses, response
      strength declines for successive pulses in the train, and the decrease becomes
      more pronounced as the stimulus intensity increases. Response decrement is thus
      greater for receptors serving the ear ipsilateral to the sound source, where
      intensity is higher, resulting in a decrease in the interaural difference in
      response strength. Sensory habituation also affects response latency, which
      increases for responses to successive sound pulses in the stimulus train. The
      change in latency is independent of intensity, and thus is similar for receptors
      serving both ears. As a result, interaural latency difference is unaffected by
      sensory habituation and may be a more reliable cue for sound localization.

PMID- 10933996
TI  - Evidence of a guanylyl cyclase natriuretic peptide receptor in the gills of the
      new zealand hagfish Eptatretus cirrhatus (Class Agnatha).
AB  - Natriuretic peptide binding sites were examined in the gills of the hagfish
      Eptatretus cirrhatus (Class Agnatha, subfamily Eptatretinae) using radio-ligand
      binding techniques, molecular cloning and guanylyl cyclase assays. Iodinated rat
      atrial natriuretic peptide ((125)I-rANP) and iodinated porcine C-type natriuretic
      peptide ((125)I-pCNP) bound specifically to the lamellar folds and cavernous
      tissue of E. cirrhatus gills, and 0.3 nmol l(-1) rat ANP competed for 50 % of
      specific (125)I-rANP binding sites. Affinity cross-linking of (125)I-rANP to gill
      membranes followed by sodium dodecylsulphate-polyacrylamide gel electrophoresis
      revealed a single binding site of 150 kDa. In the presence of Mn(2+), 0.1 nmol l(
      1) rANP inhibited cGMP production, whereas 1 micromol l(-1) rANP stimulated cGMP
      production rates. At 1 micromol l(-1), pCNP also stimulated cGMP production. The
      production of cGMP was also measured in the presence and absence of ATP with
      either Mn(2+) or Mg(2+). Reverse transcriptase polymerase chain reaction (RT-PCR)
      of hagfish gill RNA, followed by cloning and sequencing of PCR products, produced
      a partial cDNA sequence of a natriuretic peptide guanylyl cyclase receptor. The
      deduced amino acid sequence indicated 87-91 % homology with other natriuretic
      peptide guanylyl cyclase receptors. This study indicates the presence of a
      natriuretic peptide guanylyl cyclase receptor in the gills of E. cirrhatus that
      is similar to the natriuretic peptide guanylyl cyclase receptors in higher
      vertebrates. These observations demonstrate that the coupling of natriuretic
      peptide receptors with guanylyl cyclase has a long evolutionary history.

PMID- 10933998
TI  - Phenotypic plasticity of early myogenesis and satellite cell numbers in atlantic
      salmon spawning in upland and lowland tributaries of a river system.
AB  - Early myogenesis was studied in the offspring of Atlantic salmon (Salmo salar L.)
      spawning in a lowland (Sheeoch) and an upland (Baddoch) tributary of the River
      Dee System, Aberdeenshire, Scotland. Eggs from each population were incubated at
      the simulated natural thermal regimes of each stream, which was on average 2.8
      degrees C cooler for the Baddoch than for the Sheeoch. Relationships between
      muscle cellularity variables, the density of myonuclei and responses to
      temperature were investigated using multivariate statistical techniques. These
      revealed highly significant temperature effects (P<0.001) at hatch (H) and first
      feeding (FF) and significant interactions between population and temperature
      (P<0.001), indicating that Baddoch and Sheeoch salmon responded differently to
      the two temperature regimes. The total cross-sectional area of white muscle
      (WF.ta) at the adipose fin was relatively independent of temperature at hatch and
      first feeding in the Sheeoch population. In contrast, for alevins of Baddoch
      origin, WF.ta was 18.9% (H) and 30.5% (FF) higher in fish incubated at Baddoch
      than at Sheeoch temperatures. At hatch, there were 15.6% more white muscle fibres
      (WF.no) at the cooler incubation temperature in fish of Sheeoch origin and 6.0%
      more in fish of Baddoch origin. However, by first feeding, the difference in
      WF.no between temperatures had narrowed to 7.2% in the Sheeoch fish and increased
      to 17.4% in the Baddoch population. In contrast, at hatch, the density of
      myonuclei was 59.8% higher at the warmer incubation temperature in the Sheeoch
      population and 23.5% higher in the Baddoch population, but differences were less
      evident at first feeding. In Baddoch fish, 22.5% of the total muscle nuclei were
      actively dividing at first feeding, as assessed by staining for proliferating
      cell nuclear antigen (PCNA). Of the PCNA-positive nuclei, 78% were present in
      cells that stained for the c-met tyrosine kinase receptor, a marker of satellite
      cells and their division products. The proportion of c-met-positive cells
      staining for individual myogenic regulatory factors was 72.4% for the myogenic
      transcription factor MyoD, 76.3% for the myogenic transcription factor Myf-5,
      62.1% for myogenin and 48.7% for the myogenic transcription factor Myf-6. For the
      Sheeoch population, there were 26.5% more c-met-expressing (P<0.01) and 23.2%
      more myogenic-regulatory-factor-expressing (P<0.05) cells at Sheeoch than at
      Baddoch temperatures. In contrast, incubation temperature had no significant
      effects on satellite cell density in the Baddoch population.

PMID- 10933999
TI  - Early thermal experience has different effects on growth and muscle fibre
      recruitment in spring- and autumn-running Atlantic salmon populations.
AB  - The consequence of early thermal experience for subsequent growth patterns was
      investigated in Atlantic salmon (Salmo salar L.). Spring- and autumn-running
      salmon were caught in upland (Baddoch) and lowland (Sheeoch) tributaries of the
      River Dee, Aberdeenshire, Scotland, respectively, on the final stages of their
      spawning migrations. The eggs were incubated at the simulated natural temperature
      regime of each stream, which was on average 2.8 degrees C lower for the Baddoch.
      The offspring, representing 11 families per population, were transferred at first
      feeding to constant environmental conditions (12-14 degrees C; 16h:8h light:dark
      photoperiod) and reared in replicate tanks. Salmon of both populations were
      longer and heavier at 6 and 12 weeks in fish initially reared under the cooler
      Baddoch regime. Length frequency distributions became bimodal after 18 weeks, and
      only the upper growth mode was studied. Modelling of length distributions at 40
      weeks revealed significantly different patterns of muscle growth according to
      initial temperature regime, but only for the Sheeoch salmon. In fish of Sheeoch
      origin, significantly more white muscle fibres were recruited per mm(2) increase
      in myotomal cross-sectional area at Sheeoch than at Baddoch temperatures
      (P<0.01). After 40 weeks, the density of white fibres was 10.4 % higher in fish
      initially reared at the Sheeoch (533+/-6 mm(-2)) than at the Baddoch (483+/-5 mm(
      2)) thermal regimes (means +/- s.e.m., 16 fish per group; P<0.001). Muscle
      satellite cells were identified using an antibody to c-met. At 24 weeks, the
      density of muscle satellite cells was 29 % higher in Sheeoch salmon reared to
      first feeding at the temperature of their natal stream than at cooler Baddoch
      temperatures (P<0.01). In contrast, the number and size distributions of white
      muscle fibres in the myotomes of Baddoch salmon were independent of early thermal
      experience.

PMID- 10934000
TI  - Locomotor repertoire of the larval zebrafish: swimming, turning and prey capture.
AB  - Larval zebrafish (Brachydanio rerio) are a popular model system because of their
      genetic attributes, transparency and relative simplicity. They have approximately
      200 neurons that project from the brainstem into the spinal cord. Many of these
      neurons can be individually identified and laser-ablated in intact larvae. This
      should facilitate cellular-level characterization of the descending control of
      larval behavior patterns. Towards this end, we attempt to describe the range of
      locomotor behavior patterns exhibited by zebrafish larvae. Using high-speed
      digital imaging, a variety of swimming and turning behaviors were analyzed in 6-
      to 9-day-old larval fish. Swimming episodes appeared to fall into two categories,
      with the point of maximal bending of the larva's body occurring either near the
      mid-body (burst swims) or closer to the tail (slow swims). Burst swims also
      involved larger-amplitude bending, faster speeds and greater yaw than slow swims.
      Turning behaviors clearly fell into two distinct categories: fast, large-angle
      escape turns characteristic of escape responses, and much slower routine turns
      lacking the large counterbend that often accompanies escape turns. Prey-capture
      behaviors were also recorded. They were made up of simpler locomotor components
      that appeared to be similar to routine turns and slow swims. The different
      behaviors observed were analyzed with regard to possible underlying neural
      control systems. Our analysis suggests the existence of discrete sets of
      controlling neurons and helps to explain the need for the roughly 200 spinal
      projecting nerve cells in the brainstem of the larval zebrafish.

PMID- 10934001
TI  - Olfactory learning in the cricket Gryllus bimaculatus.
AB  - The olfactory learning capability of the cricket Gryllus bimaculatus was studied.
      Crickets were deprived of drinking water for 4 days and were individually trained
      to associate peppermint with water and vanilla with NaCl solution. Their odour
      preference was tested before and after training by allowing them to choose
      between peppermint or vanilla sources. The time spent visiting each source served
      as a measure of odour preference. Crickets exhibited an initial preference for
      vanilla over peppermint, but preference for the latter increased after only one
      training session. The olfactory memory formed by a single training session
      decayed with time but remained for at least 24 h. Memory formed by three training
      sessions was extremely robust, and did not decay significantly between 1 and 7
      days after training. The preference formed was easily altered by reversal
      training in which vanilla was associated with water and peppermint with saline
      solution. This study shows that crickets have a highly developed olfactory
      learning capability characterized by fast acquisition, long retention and easy
      rewriting of memory.

PMID- 10934002
TI  - The mechanics of swallowing and the muscular control of diverse behaviours in
      gopher snakes.
AB  - Snakes are excellent subjects for studying functional versatility and potential
      constraints because their movements are constrained to vertebral bending and
      twisting. In many snakes, swallowing is a kind of inside-out locomotion. During
      swallowing, vertebral bends push food from the jaws along a substantial length of
      the body to the stomach. In gopher snakes (Pituophis melanoleucus) and king
      snakes (Lampropeltis getula), swallowing often begins with lateral bending of the
      head and neck as the jaws advance unilaterally over the prey. Axial movement then
      shifts to accordion-like, concertina bending as the prey enters the oesophagus.
      Once the prey is completely engulfed, concertina bending shifts to undulatory
      bending that pushes the prey to the stomach. The shift from concertina to
      undulatory bending reflects a shift from pulling the prey into the throat (or
      advancing the mouth over the prey) to pushing it along the oesophagus towards the
      stomach. Undulatory kinematics and muscular activity patterns are similar in
      swallowing and undulatory locomotion. However, the distinct mechanical demands of
      internal versus external force exertion result in different duty factors of
      muscle activity. Feeding and locomotor movements are thus integral functions of
      the snake axial system.

PMID- 10934004
TI  - Hydrodynamics, shell shape, behavior and survivorship in the owl limpet Lottia
      gigantea.
AB  - On wave-swept rocky shores, limpets are subjected to water velocities in excess
      of 20 m s(-1), which may impose large hydrodynamic forces. Despite the extreme
      severity of this flow environment, predictions from conical models suggest that
      limpets' shells are typically far from the optimal shape that would minimize the
      risk of dislodgment, a deviation that is allowed by the high tenacity of the
      limpets' adhesive system. In this study, we test this conclusion using an actual
      limpet. The shell of Lottia gigantea differs substantially from the hydrodynamic
      optimum in that its apex is displaced anteriorly to form a plough, which is used
      to defend the limpet's territory. The hydrodynamic effects of this shape are
      similar to those observed in conical models: the animal experiences an increased
      lift when facing into the flow and a decreased lift when the flow is at its back.
      However, neither effect has a substantial impact on the risk of dislodgment. When
      the animal is stationary, its adhesion to the substratum is very strong, and its
      risk of being dislodged is small regardless of its orientation to the flow and
      despite its sub-optimal shape. In contrast, when the animal is crawling rapidly,
      its adhesion is substantially decreased, and it would probably be dislodged by
      rapid flow even if the shell were shaped optimally. The risk of dislodgment by
      waves is therefore functionally independent of shell shape. In essence, despite
      the extremely high water velocities to which this species is subjected, its shell
      has had the 'permission' of the flow environment to respond to other selective
      factors, in particular those associated with its aggressive, territorial
      behavior. The result is a shell that is both a potent territorial weapon and a
      functional (albeit less than optimal) hydrodynamic shape.

PMID- 10934003
TI  - Limits to optimization: fluid dynamics, adhesive strength and the evolution of
      shape in limpet shells.
AB  - Limpets are commonly found on wave-swept rocky shores, where they may be
      subjected to water velocities in excess of 20 m s(-1). These extreme flows can
      impose large forces (lift and drag), challenging the animal's ability to adhere
      to the substratum. It is commonly thought that the conical shape of limpet shells
      has evolved in part to reduce these hydrodynamic forces while providing a large
      aperture for adhesion. This study documents how lift and drag actually vary with
      the shape of limpet-like models and uses these data to explore the potential of
      hydrodynamic forces to serve as a selective factor in the evolution of limpet
      shell morphology. At a low ratio of shell height to shell radius, lift is the
      dominant force, while at high ratios of height to radius drag is dominant. The
      risk of dislodgment is minimized when the ratio of height to radius is 1.06 and
      the apex is in the center of the shell. Real limpets are seldom optimally shaped,
      however, with a typical height-to-radius ratio of 0.68 and an apex well anterior
      of the shell's center. The disparity between the actual and the hydrodynamically
      optimal shape of shells may be due to the high tenacity of limpets' adhesive
      system. Most limpets adhere to the substratum so strongly that they are unlikely
      to be dislodged by lift or drag regardless of the shape of their shell. The
      evolution of a tenacious adhesion system (perhaps in response to predation) has
      thus preempted selection for a hydrodynamically optimal shell, allowing the shell
      to respond to alternative selective factors.

PMID- 10934005
TI  - Acoustic identification of twelve species of echolocating bat by discriminant
      function analysis and artificial neural networks.
AB  - We recorded echolocation calls from 14 sympatric species of bat in Britain. Once
      digitised, one temporal and four spectral features were measured from each call.
      The frequency-time course of each call was approximated by fitting eight
      mathematical functions, and the goodness of fit, represented by the mean-squared
      error, was calculated. Measurements were taken using an automated process that
      extracted a single call from background noise and measured all variables without
      intervention. Two species of Rhinolophus were easily identified from call
      duration and spectral measurements. For the remaining 12 species, discriminant
      function analysis and multilayer back-propagation perceptrons were used to
      classify calls to species level. Analyses were carried out with and without the
      inclusion of curve-fitting data to evaluate its usefulness in distinguishing
      among species. Discriminant function analysis achieved an overall correct
      classification rate of 79% with curve-fitting data included, while an artificial
      neural network achieved 87%. The removal of curve-fitting data improved the
      performance of the discriminant function analysis by 2 %, while the performance
      of a perceptron decreased by 2 %. However, an increase in correct identification
      rates when curve-fitting information was included was not found for all species.
      The use of a hierarchical classification system, whereby calls were first
      classified to genus level and then to species level, had little effect on correct
      classification rates by discriminant function analysis but did improve rates
      achieved by perceptrons. This is the first published study to use artificial
      neural networks to classify the echolocation calls of bats to species level. Our
      findings are discussed in terms of recent advances in recording and analysis
      technologies, and are related to factors causing convergence and divergence of
      echolocation call design in bats.

PMID- 10934006
TI  - Action of adenosine on energetics, protein synthesis and K(+) homeostasis in
      teleost hepatocytes.
AB  - In a comparative study, we analysed the effects of adenosine on the energetics,
      protein synthesis and K(+ )homeostasis of hepatocytes from the anoxia-tolerant
      goldfish Carassius auratus and the anoxia-intolerant trout Oncorhynchus mykiss.
      The rate of oxygen consumption did not respond immediately to the addition of
      adenosine to the cells from either species, but showed a significant decrease in
      trout hepatocytes after 30 min. The anaerobic rate of lactate formation was not
      significantly affected by adenosine in goldfish hepatocytes, but was increased in
      trout cells. We also studied the effects of adenosine on the two most prominent
      ATP consumers in these cells, protein synthesis and Na(+)/K(+)-ATPase activity.
      Under aerobic conditions, adenosine inhibited protein synthesis of hepatocytes
      from goldfish by 51% and of hepatocytes from trout by 32%. During anoxia, the
      rate of protein synthesis decreased by approximately 50% in goldfish hepatocytes
      and by 90% in trout hepatocytes, and this decrease was not altered by the
      presence of adenosine. Adenosine inhibited normoxic Na(+)/K(+)-ATPase activity
      and K(+ )efflux by 20-35% in the cells of both species. An investigation into the
      mechanism underlying the inhibition of protein synthesis by adenosine indicated
      that, in the goldfish cells, adenosine acts via a membrane receptor-mediated
      pathway, i.e. the effect of adenosine was abolished by applying the A1 receptor
      antagonist 8-phenyltheophylline. In the trout, however, the uptake of adenosine
      into hepatocytes seems to be required for an effect on protein synthesis.
      [Ca(2+)](i) does not seem to be involved in the inhibition of protein synthesis
      by adenosine.

PMID- 10934007
TI  - Power output by an asynchronous flight muscle from a beetle.
AB  - The basalar muscle of the beetle Cotinus mutabilis is a large, fibrillar flight
      muscle composed of approximately 90 fibers. The paired basalars together make up
      approximately one-third of the mass of the power muscles of flight. Changes in
      twitch force with changing stimulus intensity indicated that a basalar muscle is
      innervated by at least five excitatory axons and at least one inhibitory axon.
      The muscle is an asynchronous muscle; during normal oscillatory operation there
      is not a 1:1 relationship between muscle action potentials and contractions.
      During tethered flight, the wing-stroke frequency was approximately 80 Hz, and
      the action potential frequency in individual motor units was approximately 20 Hz.
      As in other asynchronous muscles that have been examined, the basalar is
      characterized by high passive tension, low tetanic force and long twitch
      duration. Mechanical power output from the basalar muscle during imposed,
      sinusoidal strain was measured by the work-loop technique. Work output varied
      with strain amplitude, strain frequency, the muscle length upon which the strain
      was superimposed, muscle temperature and stimulation frequency. When other
      variables were at optimal values, the optimal strain for work per cycle was
      approximately 5%, the optimal frequency for work per cycle approximately 50 Hz
      and the optimal frequency for mechanical power output 60-80 Hz. Optimal strain
      decreased with increasing cycle frequency and increased with muscle temperature.
      The curve relating work output and strain was narrow. At frequencies
      approximating those of flight, the width of the work versus strain curve,
      measured at half-maximal work, was 5% of the resting muscle length. The optimal
      muscle length for work output was shorter than that at which twitch and tetanic
      tension were maximal. Optimal muscle length decreased with increasing strain. The
      curve relating work output and muscle length, like that for work versus strain,
      was narrow, with a half-width of approximately 3 % at the normal flight
      frequency. Increasing the frequency with which the muscle was stimulated
      increased power output up to a plateau, reached at approximately 100 Hz
      stimulation frequency (at 35 degrees C). The low lift generated by animals during
      tethered flight is consistent with the low frequency of muscle action potentials
      in motor units of the wing muscles. The optimal oscillatory frequency for work
      per cycle increased with muscle temperature over the temperature range tested (25
      40 degrees C). When cycle frequency was held constant, the work per cycle rose to
      an optimum with increasing temperature and then declined. We propose that there
      is a temperature optimum for work output because increasing temperature increases
      the shortening velocity of the muscle, which increases the rate of positive work
      output during shortening, but also decreases the durations of the stretch
      activation and shortening deactivation that underlie positive work output, the
      effect of temperature on shortening velocity being dominant at lower temperatures
      and the effect of temperature on the time course of activation and deactivation
      being dominant at higher temperatures. The average wing-stroke frequency during
      free flight was 94 Hz, and the thoracic temperature was 35 degrees C. The
      mechanical power output at the measured values of wing-stroke frequency and
      thoracic temperature during flight, and at optimal muscle length and strain,
      averaged 127 W kg(-1)muscle, with a maximum value of 200 W kg(-1). The power
      output from this asynchronous flight muscle was approximately twice that measured
      with similar techniques from synchronous flight muscle of insects, supporting the
      hypothesis that asynchronous operation has been favored by evolution in flight
      systems of different insect groups because it allows greater power output at the
      high contraction frequencies of flight.

PMID- 10934008
TI  - Circulatory impairment induced by exercise in the lizard Iguana iguana.
AB  - Mechanical integration of the cardiac, muscular and ventilatory pumps enables
      mammals to vary cardiac output over a wide range to match metabolic demands. We
      have found this integration lacking in a lizard (Iguana iguana) that differs from
      mammals because blood flow from the caudal body and ventilation are maximal
      after, rather than during, exercise. Because Iguana iguana are constrained from
      ventilation during intense locomotion, they appear to be unable to recruit the
      abdomen and thorax as a pump for venous return. This constraint on simultaneous
      running and costal breathing arises from their musculoskeletal design, which is
      similar to that of basal tetrapods, and so a constraint on venous return during
      exercise may be ancestral for tetrapods. We suggest that mechanical coupling of
      the pulmonary and cardiac pumps may have been important for the evolution of high
      speed locomotor stamina in terrestrial vertebrates.

PMID- 10934009
TI  - Geographic and altitudinal variation in water balance and metabolic rate in a
      California grasshopper, Melanoplus sanguinipes.
AB  - The importance of respiratory patterns and the physical properties of cuticular
      lipids to insect water balance were investigated in natural populations of the
      grasshopper Melanoplus sanguinipes. I specifically test the hypotheses that
      patterns of discontinuous ventilation affect water loss and that increased
      amounts and melting points of cuticular lipid reduce water loss. Using flow
      through respirometry, rates of water loss and carbon dioxide release from
      grasshoppers were quantified at 25, 35 and 42 degrees C. Populations displayed
      substantial variation, with high-elevation populations exhibiting the greatest
      water loss and metabolic rates. Behavior leading to discontinuous gas exchange
      was observed in several populations, but its occurrence decreased dramatically at
      high temperatures and was not correlated with a reduction in the rate of water
      loss. The amount and melting point of cuticular lipids were determined for each
      individual using gas chromatography and Fourier-transform infrared spectroscopy.
      Increased amounts and higher melting points of cuticular lipids were strongly
      correlated with lower rates of water loss in populations. I show that
      discontinuous gas exchange is unlikely to be a mechanism for reducing water loss
      in these insects and that the lipid properties are primarily responsible for
      variation in overall water loss rates.

PMID- 10934011
TI  - A role for the rice homeobox gene Oshox1 in provascular cell fate commitment.
AB  - The vascular tissues of plants form a network of interconnected cell files
      throughout the plant body. The transition from a genetically totipotent
      meristematic precursor to different stages of a committed procambial cell, and
      its subsequent differentiation into a mature vascular element, involves
      developmental events whose molecular nature is still mostly unknown. The rice
      protein Oshox1 is a member of the homeodomain leucine zipper family of
      transcription factors. Here we show that the strikingly precise onset of Oshox1
      gene expression marks critical, early stages of provascular ontogenesis in which
      the developmental fate of procambial cells is specified but not yet stably
      determined. This suggests that the Oshox1 gene may be involved in the
      establishment of the conditions required to restrict the developmental potential
      of procambial cells. In support of this hypothesis, ectopic expression of Oshox1
      in provascular cells that normally do not yet express this gene results in
      anticipation of procambial cell fate commitment, eventually culminating in
      premature vascular differentiation. Oshox1 represents the first example of a
      transcription factor whose function can be linked to specification events
      mediating provascular cell fate commitment.

PMID- 10934010
TI  - The olfactory placodes of the zebrafish form by convergence of cellular fields at
      the edge of the neural plate.
AB  - The primary olfactory sensory system is part of the PNS that develops from
      ectodermal placodes. Several cell types, including sensory neurons and support
      cells, differentiate within the olfactory placode to form the mature olfactory
      organ. The olfactory placodes are thought to arise from lateral regions of the
      anterior neural plate, which separate from the plate through differential cell
      movements. We determined the origins of the olfactory placodes in zebrafish by
      labeling cells along the anterior-lateral edge of the neural plate at times
      preceding the formation of the olfactory placodes and examining the later fates
      of the labeled cells. Surprisingly, we found that the olfactory placode arises
      from a field of cells, not from a discrete region of the anterior neural plate.
      This field extends posteriorly to the anterior limits of cranial neural crest and
      is bordered medially by telencephalic precursors. Cells giving rise to progeny in
      both the olfactory organ and telencephalon express the distal-less 3 gene.
      Furthermore, we found no localized pockets of cell division in the anterior
      lateral neural plate cells preceding the appearance of the olfactory placode. We
      suggest that the olfactory placodes arise by anterior convergence of a field of
      lateral neural plate cells, rather than by localized separation and proliferation
      of a discrete group of cells.

PMID- 10934012
TI  - Roles of BMP signaling and Nkx2.5 in patterning at the chick midgut-foregut
      boundary.
AB  - Patterning of the gut into morphologically distinct regions results from the
      appropriate factors being expressed in strict spatial and temporal patterns to
      assign cells their fates in development. Often, the boundaries of gene expression
      early in development correspond to delineations between different regions of the
      adult gut. For example, Bmp4 is expressed throughout the hindgut and midgut, but
      is not expressed in the early gizzard. Ectopic BMP4 in the gizzard caused a
      thinning of the muscularis. To understand this phenotype we examined the
      expression of the receptors transducing BMP signaling during gut development. We
      find that the BMP receptors are differentially expressed in distinct regions of
      the chicken embryonic gut. By using constitutively activated versions of the BMP
      type I receptors, we find that the BMP receptors act similarly to BMP4 in the
      gizzard when ectopically expressed. We show that the mesodermal thinning seen
      upon ectopic BMP signaling is due to an increase in apoptosis and a decrease in
      proliferation within the gizzard mesoderm. The mesodermal thinning is
      characterized by a disorganization and lack of differentiation of smooth muscle
      in the gizzard mesoderm. Further, ectopic BMP receptors cause an upregulation of
      Nkx2.5, the pyloric sphincter marker, similar to that seen with ectopic BMP4.
      This upregulation of Nkx2.5 is a cell-autonomous event within the mesoderm of the
      gizzard. We also find that Nkx2.5 is necessary and sufficient for establishing
      aspects of pyloric sphincter differentiation.

PMID- 10934013
TI  - RNAi analysis of Deformed, proboscipedia and Sex combs reduced in the milkweed
      bug Oncopeltus fasciatus: novel roles for Hox genes in the hemipteran head.
AB  - Insects have evolved a large variety of specialized feeding strategies, with a
      corresponding variability in mouthpart morphology. We have, however, little
      understanding of the developmental mechanisms that underlie this diversity. Until
      recently it was difficult to perform any analysis of gene function outside of the
      genetic model insects Drosophila melanogaster and Tribolium castaneum. In this
      paper, we report the use of dsRNA-mediated interference (RNAi) to dissect gene
      function in the development of the milkweed bug Oncopeltus fasciatus, which has
      specialized suctorial mouthparts. The Hox genes Deformed (Dfd), proboscipedia
      (pb) and Sex combs reduced (Scr) have previously been shown to be expressed in
      the gnathal appendages of this species. Strikingly, the milkweed bug was found to
      have an unusual expression pattern of pb. Here, by analyzing single and
      combination RNAi depletions, we find that Dfd, pb and Scr are used in the
      milkweed bug to specify the identity of the mouthparts. The exact roles of the
      genes, however, are different from what is known in the two genetic model
      insects. The maxillary appendages in the bug are determined by the activities of
      the genes Dfd and Scr, rather than Dfd and pb as in the fly and beetle. The
      mandibular appendages are specified by Dfd, but their unique morphology in
      Oncopeltus suggests that Dfd's target genes are different. As in flies and
      beetles, the labium is specified by the combined activities of pb and Scr, but
      again, the function of pb appears to be different. Additionally, the regulatory
      control of pb by the other two genes seems to be different in the bug than in
      either of the other species. These novelties in Hox function, expression pattern
      and regulatory relationships may have been important for the evolution of the
      unique Hemipteran head.

PMID- 10934014
TI  - decapentaplegic is a direct target of dTcf repression in the Drosophila visceral
      mesoderm.
AB  - Drosophila T cell factor (dTcf) mediates transcriptional activation in the
      presence of Wingless signalling and repression in its absence. Wingless
      signalling is required for the correct expression of decapentaplegic (dpp), a
      Transforming Growth Factor (beta) family member, in parasegments 3 and 7 of the
      Drosophila visceral mesoderm. Here we demonstrate that a dpp enhancer element,
      which directs expression of a reporter gene in the visceral mesoderm in a pattern
      indistinguishable from dpp, has two functional dTcf binding sites. Mutations that
      reduce or eliminate Wingless signalling abolish dpp reporter gene expression in
      parasegment 3 and reduce it in parasegment 7 while ectopic expression of Wingless
      signalling components expand reporter gene expression anteriorly in the visceral
      mesoderm. However, mutation of the dTcf binding sites in the dpp enhancer results
      in ectopic expression of reporter gene expression throughout the visceral
      mesoderm, with no diminution of expression in the endogenous sites of expression.
      These results demonstrate that the primary function of dTcf binding to the dpp
      enhancer is repression throughout the visceral mesoderm and that activation by
      Wingless signalling is probably not mediated via these dTcf binding sites to
      facilitate correct dpp expression in the visceral mesoderm.

PMID- 10934015
TI  - Functional equivalence of the transcription factors Pax2 and Pax5 in mouse
      development.
AB  - Pax2 and Pax5 arose by gene duplication at the onset of vertebrate evolution and
      have since diverged in their developmental expression patterns. They are
      expressed in different organs of the mouse embryo except for their coexpression
      at the midbrain-hindbrain boundary (MHB), which functions as an organizing center
      to control midbrain and cerebellum development. During MHB development, Pax2
      expression is initiated prior to Pax5 transcription, and Pax2(-/-) embryos fail
      to generate the posterior midbrain and cerebellum, whereas Pax5(-/-) mice exhibit
      only minor patterning defects in the same brain regions. To investigate whether
      these contrasting phenotypes are caused by differences in the temporal expression
      or biochemical activity of these two transcription factors, we have generated a
      knock-in (ki) mouse, which expresses a Pax5 minigene under the control of the
      Pax2 locus. Midbrain and cerebellum development was entirely rescued in
      Pax2(5ki/5ki) embryos. Pax5 could furthermore completely substitute for the Pax2
      function during morphogenesis of the inner ear and genital tracts, despite the
      fact that the Pax5 transcript of the Pax2(5ki )allele was expressed only at a
      fivefold lower level than the wild-type Pax2 mRNA. As a consequence, the Pax2(5ki
      )allele was able to rescue most but not all Pax2 mutant defects in the developing
      eye and kidney, both of which are known to be highly sensitive to Pax2 protein
      dosage. Together these data demonstrate that the transcription factors Pax2 and
      Pax5 have maintained equivalent biochemical functions since their divergence
      early in vertebrate evolution.

PMID- 10934016
TI  - Zebrafish kit mutation reveals primary and secondary regulation of melanocyte
      development during fin stripe regeneration.
AB  - Fin regeneration in adult zebrafish is accompanied by re-establishment of the
      pigment stripes. To understand the mechanisms underlying fin stripe regeneration
      and regulation of normal melanocyte stripe morphology, we investigated the
      origins of melanocytes in the regenerating fin and their requirement for the kit
      receptor tyrosine kinase. Using pre-existing melanin as a lineage tracer, we show
      that most fin regeneration melanocytes develop from undifferentiated precursors,
      rather than from differentiated melanocytes. Mutational analysis reveals two
      distinct classes of regeneration melanocytes. First, an early regeneration class
      develops dependent on kit function. In the absence of kit function and kit
      dependent melanocytes, a second class of melanocytes develops at later stages of
      regeneration. This late kit-independent class of regeneration melanocytes has
      little or no role in wild-type fin stripe development, thus revealing a secondary
      mode for regulation of fin stripes. Expression of melanocyte markers in
      regenerating kit mutant fins suggests that kit normally acts after mitf and
      before dct to promote development of the primary kit-dependent melanocytes. kit
      dependent and kit-independent melanocytes are also present during fin stripe
      ontogeny in patterns similar to those observed during regeneration.

PMID- 10934017
TI  - CHORIPETALA and DESPENTEADO: general regulators during plant development and
      potential floral targets of FIMBRIATA-mediated degradation.
AB  - Two Antirrhinum majus mutants, choripetala (cho) and despenteado (desp), exhibit
      identical highly pleiotropic phenotypes including petaloid transformation of
      first whorl floral organs, narrowing of both vegetative and floral organs,
      reduction in carpel size and fertility and delayed germination. The petaloid
      first whorl results from ectopic expression of the class B genes DEFICIENS and
      GLOBOSA and is correlated with the ectopic expression of the proposed class B/C
      gene regulator FIMBRIATA (FIM). Ectopic class B gene expression is apparent from
      the earliest point at which class B gene transcription can be detected in the
      wild type, indicating that the pre-patterning of the class B domain has been
      disrupted in these mutants. Single and double mutant analyses indicate that CHO
      and DESP also play a role in regulation of the class C domain. Interestingly, the
      cho and desp mutations partially suppress the phenotype of fim null mutants,
      suggesting that the F-box protein FIM may target a member of the CHO/DESP pathway
      for degradation. We propose that CHO and DESP are members of a 'basal regulatory
      function' influencing many processes throughout plant development and in
      particular are directly or indirectly required for the repression of class B and
      C genes during early stages of flower development.

PMID- 10934018
TI  - Some fly sensory organs are gliogenic and require glide/gcm in a precursor that
      divides symmetrically and produces glial cells.
AB  - In flies, the choice between neuronal and glial fates depends on the asymmetric
      division of multipotent precursors, the neuroglioblast of the central nervous
      system and the IIb precursor of the sensory organ lineage. In the central nervous
      system, the choice between the two fates requires asymmetric distribution of the
      glial cell deficient/glial cell missing (glide/gcm) RNA in the neuroglioblast.
      Preferential accumulation of the transcript in one of the daughter cells results
      in the activation of the glial fate in that cell, which becomes a glial
      precursor. Here we show that glide/gcm is necessary to induce glial
      differentiation in the peripheral nervous system. We also present evidence that
      glide/gcm RNA is not necessary to induce the fate choice in the peripheral
      multipotent precursor. Indeed, glide/gcm RNA and protein are first detected in
      one daughter of IIb but not in IIb itself. Thus, glide/gcm is required in both
      central and peripheral glial cells, but its regulation is context dependent.
      Strikingly, we have found that only subsets of sensory organs are gliogenic and
      express glide/gcm. The ability to produce glial cells depends on fixed, lineage
      related, cues and not on stochastic decisions. Finally, we show that after
      glide/gcm expression has ceased, the IIb daughter migrates and divides
      symmetrically to produce several mature glial cells. Thus, the glide/gcm
      expressing cell, also called the fifth cell of the sensory organ, is indeed a
      glial precursor. This is the first reported case of symmetric division in the
      sensory organ lineage. These data indicate that the organization of the fly
      peripheral nervous system is more complex than previously thought.

PMID- 10934020
TI  - The Arabidopsis COMATOSE locus regulates germination potential.
AB  - Mutation of the COMATOSE locus in Arabidopsis results in a marked reduction in
      germination potential. Whilst the morphology of comatose (cts) embryos is not
      altered, physiological analysis reveals that mature cts seeds do not respond to
      gibberellin. Prolonged chilling of imbibed seeds only partially restores
      germination potential, and seeds do not after ripen. Genetic analysis shows that
      the cts phenotype is expressed in the embryo and phenotypic differences between
      wild-type and mutant plants were not observed during other stages of plant growth
      and development. Therefore cts represents a new class of mutant, with a specific
      lesion that results in severely impaired germination potential. Genetic
      interactions were analysed between cts and loci that regulate embryo maturation,
      and abscisic acid biosynthesis and perception. Results from these studies showed
      that the cts mutant phenotype required the wild-type action of these loci, and
      suggested that CTS exerts a repressive function on these loci. A model is
      presented postulating that CTS promotes increased germination potential, and
      represses embryo dormancy. These functions of CTS may result in the removal of
      embryo dormancy as a prerequisite to germination.

PMID- 10934019
TI  - The expression of Myf5 in the developing mouse embryo is controlled by discrete
      and dispersed enhancers specific for particular populations of skeletal muscle
      precursors.
AB  - The development of skeletal muscle in vertebrate embryos is controlled by a
      transcriptional cascade that includes the four myogenic regulatory factors Myf5,
      Myogenin, MRF4 and MyoD. In the mouse embryo, Myf5 is the first of these factors
      to be expressed and mutational analyses suggest that this protein acts early in
      the process of commitment to the skeletal muscle fate. We have therefore analysed
      the regulation of Myf5 gene expression using transgenic technology and find that
      its control is markedly different from that of the other two myogenic regulatory
      factor genes previously analysed, Myogenin and MyoD. We show that Myf5 is
      regulated through a number of distinct and discrete enhancers, dispersed
      throughout 14 kb spanning the MRF4/Myf5 locus, each of which drives reporter gene
      expression in a particular subset of skeletal muscle precursors. This region
      includes four separate enhancers controlling expression in the epaxial muscle
      precursors of the body, some hypaxial precursors of the body, some facial muscles
      and the central nervous system. These elements separately or together are unable
      to drive expression in the cells that migrate to the limb buds and in some other
      muscle subsets and to correctly maintain expression at late times. We suggest
      that this complex mechanism of control has evolved because different inductive
      signals operate in each population of muscle precursors and thus distinct
      enhancers, and cognate transcription factors, are required to interpret them.

PMID- 10934021
TI  - EGF receptor attenuates Dpp signaling and helps to distinguish the wing and leg
      cell fates in Drosophila.
AB  - Wing and leg precursors of Drosophila are recruited from a common pool of
      ectodermal cells expressing the homeobox gene Dll. Induction by Dpp promotes this
      cell fate decision toward the wing and proximal leg. We report here that the
      receptor tyrosine kinase EGFR antagonizes the wing-promoting function of Dpp and
      allows recruitment of leg precursor cells from uncommitted ectodermal cells. By
      monitoring the spatial distribution of cells responding to Dpp and EGFR, we show
      that nuclear transduction of the two signals peaks at different position along
      the dorsoventral axis when the fates of wing and leg discs are specified and that
      the balance of the two signals assessed within the nucleus determines the number
      of cells recruited to the wing. Differential activation of the two signals and
      the cross talk between them critically affect this cell fate choice.

PMID- 10934022
TI  - Molecular characterization of the TrkA/NGF receptor minimal enhancer reveals
      regulation by multiple cis elements to drive embryonic neuron expression.
AB  - Neural development relies on stringent regulation of key genes that mediate
      specialized function. TrkA is primarily expressed in neural crest-derived sensory
      and sympathetic neurons where it transmits critical survival information. We have
      identified a 457 base pair sequence upstream of the murine first TrkA coding exon
      that is conserved in human and in chick, and is sufficient for expression in the
      correct cells with appropriate timing. Mutation analysis of consensus
      transcription factor binding domains within the minimal enhancer reveals a
      complex positive regulation that includes sites required for global expression
      and sites that are specifically required for DRG, trigeminal or sympathetic
      expression. These results provide a foundation for identification of the
      transcriptional machinery that specifies neurotrophin receptor expression.

PMID- 10934023
TI  - Dual origin and segmental organisation of the avian scapula.
AB  - Bones of the postcranial skeleton of higher vertebrates originate from either
      somitic mesoderm or somatopleural layer of the lateral plate mesoderm.
      Controversy surrounds the origin of the scapula, a major component of the
      shoulder girdle, with both somitic and lateral plate origins being proposed.
      Abnormal scapular development has been described in the naturally occurring
      undulated series of mouse mutants, which has implicated Pax1 in the formation of
      this bone. Here we addressed the development of the scapula, firstly, by
      analysing the relationship between Pax1 expression and chondrogenesis and,
      secondly, by determining the developmental origin of the scapula using chick
      quail chimeric analysis. We show the following. (1) The scapula develops in a
      rostral-to-caudal direction and overt chondrification is preceded by an
      accumulation of Pax1-expressing cells. (2) The scapular head and neck are of
      lateral plate mesodermal origin. (3) In contrast, the scapular blade is composed
      of somitic cells. (4) Unlike the Pax1-positive cells of the vertebral column,
      which are of sclerotomal origin, the Pax1-positive cells of the scapular blade
      originate from the dermomyotome. (5) Finally, we show that cells of the scapular
      blade are organised into spatially restricted domains along its rostrocaudal axis
      in the same order as the somites from which they originated. Our results imply
      that the scapular blade is an ossifying muscular insertion rather than an
      original skeletal element, and that the scapular head and neck are homologous to
      the 'true coracoid' of higher vertebrates.

PMID- 10934024
TI  - Timely translation during the mouse oocyte-to-embryo transition.
AB  - In the mouse, completion of oocyte maturation and the initiation of
      preimplantation development occur during transcriptional silence and depend on
      the presence and translation of stored mRNAs transcribed in the growing oocyte.
      The Spin gene has three transcripts, each with an identical open reading frame
      and a different 3' untranslated region (UTR). (Beta)-galactosidase-tagged
      reporter transcripts containing each of the different Spin 3'UTRs were injected
      into oocytes and zygotes and (beta)-galactosidase activity was monitored. Results
      from these experiments suggest that differential polyadenylation and translation
      occurs at two critical points in the oocyte-to-embryo transition - upon oocyte
      maturation and fertilization - and is dependent on sequences in the 3'UTR. The
      stability and mobility shifts of ten other maternal transcripts were monitored by
      reprobing a northern blot of oocytes and embryos collected at 12 hour intervals
      after fertilization. Some are more stable than others and the upward mobility
      shift associated with polyadenylation correlates with the presence of cytoplasmic
      polyadenylation elements (CPEs) within about 120 nucleotides of the nuclear
      polyadenylation signal. A survey of the 3' UTRs of expressed sequence tag
      clusters from a mouse 2-cell stage cDNA library indicates that about one third
      contain CPEs. We suggest that differential transcript stability and a
      translational control program can supply the diversity of protein products
      necessary for oocyte maturation and the initiation of development.

PMID- 10934025
TI  - Wnt/(beta)-catenin signaling regulates the expression of the homeobox gene Cdx1
      in embryonic intestine.
AB  - During mammalian development, the Cdx1 homeobox gene exhibits an early period of
      expression when the embryonic body axis is established, and a later period where
      expression is restricted to the embryonic intestinal endoderm. Cdx1 expression is
      maintained throughout adulthood in the proliferative cell compartment of the
      continuously renewed intestinal epithelium, the crypts. In this study, we provide
      evidence in vitro and in vivo that Cdx1 is a direct transcriptional target of the
      Wnt/(beta)-catenin signaling pathway. Upon Wnt stimulation, expression of Cdx1
      can be induced in mouse embryonic stem (ES) cells as well as in undifferentiated
      rat embryonic endoderm. Tcf4-deficient mouse embryos show abrogation of Cdx1
      protein in the small intestinal epithelium, making Tcf4 the likely candidate to
      transduce Wnt signal in this part of gut. The promoter region of the Cdx1 gene
      contains several Tcf-binding motifs, and these bind Tcf/Lef1/(beta)-catenin
      complexes and mediate (beta)-catenin-dependent transactivation. The
      transcriptional regulation of the homeobox gene Cdx1 in the intestinal epithelium
      by Wnt/(beta)-catenin signaling underlines the importance of this signaling
      pathway in mammalian endoderm development.

PMID- 10934026
TI  - sucker encodes a zebrafish Endothelin-1 required for ventral pharyngeal arch
      development.
AB  - Mutation of sucker (suc) disrupts development of the lower jaw and other ventral
      cartilages in pharyngeal segments of the zebrafish head. Our sequencing,
      cosegregation and rescue results indicate that suc encodes an Endothelin-1 (Et
      1). Like mouse and chick Et-1, suc/et-1 is expressed in a central core of arch
      paraxial mesoderm and in arch epithelia, both surface ectoderm and pharyngeal
      endoderm, but not in skeletogenic neural crest. Long before chondrogenesis,
      suc/et-1 mutant embryos have severe defects in ventral arch neural crest
      expression of dHAND, dlx2, msxE, gsc, dlx3 and EphA3 in the anterior arches.
      Dorsal expression patterns are unaffected. Later in development, suc/et-1 mutant
      embryos display defects in mesodermal and endodermal tissues of the pharynx.
      Ventral premyogenic condensations fail to express myoD, which correlates with a
      ventral muscle defect. Further, expression of shh in endoderm of the first
      pharyngeal pouch fails to extend as far laterally as in wild types. We use mosaic
      analyses to show that suc/et-1 functions nonautonomously in neural crest cells,
      and is thus required in the environment of postmigratory neural crest cells to
      specify ventral arch fates. Our mosaic analyses further show that suc/et-1
      nonautonomously functions in mesendoderm for ventral arch muscle formation.
      Collectively our results support a model for dorsoventral patterning of the
      gnathostome pharyngeal arches in which Et-1 in the environment of the
      postmigratory cranial neural crest specifies the lower jaw and other ventral arch
      fates.

PMID- 10934027
TI  - GATA2 is required for the generation of V2 interneurons.
AB  - During embryogenesis, transcription factor GATA2 is expressed in a variety of
      distinct cell types, and earlier experiments showed that GATA2 is a vital
      regulator of both hematopoiesis and urogenital development. Despite the fact that
      GATA2 is expressed early and abundantly in the nervous system, there has been no
      demonstration of its direct participation in neurogenesis. We show here that
      GATA2 is expressed in the ventral spinal cord exclusively in newly generated V2
      interneurons, suggesting that GATA2 might be required for the generation of this
      discrete neuronal population. Proof for this hypothesis was provided by showing
      that the number of cells expressing V2 neuronal markers was drastically
      diminished in gata2 null mutant embryos. The tissue-specific enhancer that
      directs gata2 transcription specifically in V2 neurons was localized to a 190 bp
      intragenic element lying within gata2 intron 5, and this element is both
      necessary and sufficient to confer GATA2 spinal cord expression. The
      identification of a V2-specific enhancer should allow fundamental new insight
      into the genetic hierarchy of regulatory events that govern neurogenesis in a
      well-defined cell lineage.

PMID- 10934028
TI  - Reconciling different models of forebrain induction and patterning: a dual role
      for the hypoblast.
AB  - Several models have been proposed for the generation of the rostral nervous
      system. Among them, Nieuwkoop's activation/transformation hypothesis and
      Spemann's idea of separate head and trunk/tail organizers have been particularly
      favoured recently. In the mouse, the finding that the visceral endoderm (VE) is
      required for forebrain development has been interpreted as support for the latter
      model. Here we argue that the chick hypoblast is equivalent to the mouse VE,
      based on fate, expression of molecular markers and characteristic anterior
      movements around the time of gastrulation. We show that the hypoblast does not
      fit the criteria for a head organizer because it does not induce neural tissue
      from naive epiblast, nor can it change the regional identity of neural tissue.
      However, the hypoblast does induce transient expression of the early markers Sox3
      and Otx2. The spreading of the hypoblast also directs cell movements in the
      adjacent epiblast, such that the prospective forebrain is kept at a distance from
      the organizer at the tip of the primitive streak. We propose that this movement
      is important to protect the forebrain from the caudalizing influence of the
      organizer. This dual role of the hypoblast is more consistent with the Nieuwkoop
      model than with the notion of separate organizers, and accommodates the available
      data from mouse and other vertebrates.

PMID- 10934029
TI  - A phospholipid kinase regulates actin organization and intercellular bridge
      formation during germline cytokinesis.
AB  - The endgame of cytokinesis can follow one of two pathways depending on
      developmental context: resolution into separate cells or formation of a stable
      intercellular bridge. Here we show that the four wheel drive (fwd) gene of
      Drosophila melanogaster is required for intercellular bridge formation during
      cytokinesis in male meiosis. In fwd mutant males, contractile rings form and
      constrict in dividing spermatocytes, but cleavage furrows are unstable and
      daughter cells fuse together, producing multinucleate spermatids. fwd is shown to
      encode a phosphatidylinositol 4-kinase (PI 4-kinase), a member of a family of
      proteins that perform the first step in the synthesis of the key regulatory
      membrane phospholipid PIP2. Wild-type activity of the fwd PI 4-kinase is required
      for tyrosine phosphorylation in the cleavage furrow and for normal organization
      of actin filaments in the constricting contractile ring. Our results suggest a
      critical role for PI 4-kinases and phosphatidylinositol derivatives during the
      final stages of cytokinesis.

PMID- 10934031
TI  - <FONT COLOR=#0E3193>Triplet deciphers genomes
AB  - particularly up to date features, Gerald Karp's book includes a section in the
      Cancer chapter on angiogenesis, as does Lodish et al., but in Karp the
      information imparted extends to a scheme showing the effect of endostatin on
      mouse tumours, replete with photographs of mice from such an experiment. All of
      this has resulted in a book that is focused but highly informative and a delight
      to browse through. If it appears by now that your reviewer is suggesting you
      should dash out and buy all three of these books, I can only admit that I am
      delighted to have them on my shelf. If you have to choose, for fundamental
      biochemical science with a fair degree of breadth thrown in it has to be
      Lehninger. For a comprehensive molecular biology course Lodish et al. is the
      equal of anything else on the market. For a broad grounding in cell and molecular
      biology that will appeal especially to medical students go for Karp.

PMID- 10934030
TI  - Serrate and Notch specify cell fates in the heart field by suppressing
      cardiomyogenesis.
AB  - Notch signaling mediates numerous developmental cell fate decisions in organisms
      ranging from flies to humans, resulting in the generation of multiple cell types
      from equipotential precursors. In this paper, we present evidence that activation
      of Notch by its ligand Serrate apportions myogenic and non-myogenic cell fates
      within the early Xenopus heart field. The crescent-shaped field of heart mesoderm
      is specified initially as cardiomyogenic. While the ventral region of the field
      forms the myocardial tube, the dorsolateral portions lose myogenic potency and
      form the dorsal mesocardium and pericardial roof (Raffin, M., Leong, L. M.,
      Rones, M. S., Sparrow, D., Mohun, T. and Mercola, M. (2000) Dev. Biol., 218, 326
      340). The local interactions that establish or maintain the distinct myocardial
      and non-myocardial domains have never been described. Here we show that Xenopus
      Notch1 (Xotch) and Serrate1 are expressed in overlapping patterns in the early
      heart field. Conditional activation or inhibition of the Notch pathway with
      inducible dominant negative or active forms of the RBP-J/Suppressor of Hairless
      [Su(H)] transcription factor indicated that activation of Notch feeds back on
      Serrate1 gene expression to localize transcripts more dorsolaterally than those
      of Notch1, with overlap in the region of the developing mesocardium. Moreover,
      Notch pathway activation decreased myocardial gene expression and increased
      expression of a marker of the mesocardium and pericardial roof, whereas
      inhibition of Notch signaling had the opposite effect. Activation or inhibition
      of Notch also regulated contribution of individual cells to the myocardium.
      Importantly, expression of Nkx2. 5 and Gata4 remained largely unaffected,
      indicating that Notch signaling functions downstream of heart field
      specification. We conclude that Notch signaling through Su(H) suppresses
      cardiomyogenesis and that this activity is essential for the correct
      specification of myocardial and non-myocardial cell fates.

PMID- 10934032
TI  - Do growth and cell division rates determine cell size in multicellular organisms?
AB  - Studies in yeast have provided some clues to how cell size might be determined in
      unicellular eukaryotes; yet little attention has been paid to this issue in
      multicellular organisms. Reproducible cell sizes might be achieved in the
      dividing cells of multicellular organisms by the coordination of growth with cell
      division. Recently, mutations in genes encoding homologues of components of the
      mammalian insulin/phosphoinositide 3-kinase signalling pathway have been shown to
      affect organ growth and cell size during Drosophila melanogaster imaginal disc
      development. The data suggest that signalling through this pathway alters cell
      size because it primarily affects the growth of these organs (i.e. their increase
      in mass) and does not have a proportional impact on cell division. These
      observations are in keeping with the hypothesis that growth and cell division are
      regulated independently, and that cell size is just a consequence of the rate at
      which tissues grow and the cells within them divide. However, signalling through
      this pathway can affect cell cycle phasing and at least influence cell division.
      These interactions may provide a means of coordinating growth and cell division,
      such that cells divide only when they are above a minimum size.

PMID- 10934033
TI  - Roles of phospholipid signaling in chemoattractant-induced responses.
AB  - Chemoattractants, including chemokines, play a central role in regulation of
      inflammatory reactions by attracting and activating leukocytes. These molecules
      have been found to regulate metabolism of phosphatidylinositol 4,5-bisphosphate
      (PtdIns(4,5)P(2)) via phospholipase C (PLC) and phosphoinositide 3-kinase (PI3K).
      Recent studies of mouse lines that lack PLC-(beta)2, PLC-(beta)3, or PI3K(gamma)
      demonstrate that chemoattractants act through PLC-(beta)2 and PLC-(beta)3 to
      hydrolyze PtdIns(4,5)P(2) and through PI3K(gamma) to phosphorylate
      PtdIns(4,5)P(2) in mouse neutrophils. These studies also confirmed the importance
      and revealed new roles of these signaling pathways in chemoattractant-induced
      responses.

PMID- 10934034
TI  - Effector caspases are dispensable for the early nuclear morphological changes
      during chemical-induced apoptosis.
AB  - Nuclear morphological changes during apoptosis are very distinct and effector
      caspases have been implicated to play a central role in these processes. To
      investigate this in greater detail we examined the effect of blocking caspase
      activity and its activation on the nuclear morphological change in Jurkat T cells
      undergoing apoptosis after staurosporine treatment. In the presence of caspase
      inhibitors, like benzyloxycarbonyl-Val-Ala-Asp fluoro-methylketone (z-VAD-FMK), N
      acetyl Tyr-Val-Ala-Asp chloromethylketone (Ac-YVAD-CMK) and benzyloxy-carbonyl
      Asp-Glu-Val-Asp (OMe) fluoromethylketone (z-DEVD-FMK), staurosporine-treated
      Jurkat cells displayed a nuclear morphological change distinct from that of
      normal and apoptotic cells. This nuclear morphological change is an early event,
      characterised by convoluted nuclei with cavitations, and clumps of chromatin
      abutting to inner regions of the nuclear envelope between the nuclear pores. Both
      the nuclear envelope and endoplasmic reticulum were grossly dilated. This pre
      apoptotic nuclear change precedes the externalisation of phosphatidylserine,
      chromatin condensation and DNA laddering, and can be dissociated from the
      formation of high molecular weight DNA fragments and cell shrinkage. Although
      cytochrome c efflux from the mitochondria and the processing of caspase-3 were
      observed in Jurkat cells with pre-apoptotic nuclear morphology, caspase-2, -6, -7
      and -8 were not activated. In the presence of z-DEVD-FMK or Ac-YVAD-CMK, caspase
      3 was processed to both the p17 and p20 fragments in staurosporine-treated cells,
      but only to p20 fragment in the presence of z-VAD-FMK. However, the caspase-3
      substrate, poly(ADP ribose) polymerase was not cleaved in the presence of z-VAD
      FMK, despite >70% of the cells have pre-apoptotic nuclei. In addition, caspase-3
      null MCF-7 cells also undergo pre-apoptotic nuclear change when treated with
      staurosporine in the presence of caspase inhibitors, indicating that caspase-3 is
      not required for the early nuclear morphological change in cells undergoing
      apoptosis. Although cell death in staurosporine-treated Jurkat cells was markedly
      delayed, they eventually die without discernible downstream apoptotic features.
      Other apoptotic stimuli like etoposide and the heavy metal chelator, N,N,N',N'
      tetrakis (2-pyridylmethyl) ethylenediamine also induced this nuclear
      morphological change in Jurkat cells in the presence of z-VAD-FMK. In summary,
      the effector caspases are not involved in early nuclear morphological change,
      which precedes the conventional hallmark morphological changes associated with
      chemical-induced apoptosis.

PMID- 10934035
TI  - Membrane recruitment of Rac1 triggers phagocytosis.
AB  - Rac1 is a &Rgr;-family GTP-binding protein that controls lamellipodia formation
      and membrane ruffling in fibroblasts. Recently, Rac1 and Cdc42, another member of
      the &Rgr;-family, have been shown to regulate Fc receptor-mediated phagocytosis
      in macrophages by controlling different steps of membrane and actin dynamics
      leading to particle engulfment. Here, we investigated the function of Rac1 using
      a membrane recruitment system that mimics phagocytosis. Recruitment of an
      activated Rac1 protein to the cytoplasmic domain of an engineered membrane
      receptor by using rapamycin as a bridge induces ingestion of latex beads bound to
      the receptor. Rac1-mediated bead uptake depends on actin polymerisation since
      actin filaments accumulate at the bead/membrane binding sites and internalisation
      is inhibited by cytochalasin D. Internalisation is also abolished upon
      substitution of Phe37 to Leu in the Rac1 effector region. Our results indicate
      that by promoting actin polymerisation at particle attachment sites, Rac1 by
      acting through specific downstream effectors induces plasma membrane remodeling
      that allows particle internalisation in a membrane-enclosed phagosome.

PMID- 10934036
TI  - Ligand-induced internalization of neurotensin in transfected COS-7 cells:
      differential intracellular trafficking of ligand and receptor.
AB  - The neuropeptide neurotensin (NT) is known to be internalized in a receptor
      mediated fashion into its target cells. To gain insight into the mechanisms
      underlying this process, we monitored in parallel the migration of the NT1
      neurotensin receptor subtype and a fluorescent analog of NT (fluo-NT) in COS-7
      cells transfected with a tagged NT1 construct. Fluo-NT internalization was
      prevented by hypertonic sucrose, potassium depletion and cytosol acidification,
      demonstrating that it proceeded via clathrin-coated pits. Within 0-30 minutes,
      fluo-NT accumulated together with its receptor in Acridine Orange-positive,
      acidic organelles. These organelles concentrated transferrin and immunostained
      positively for rab 5A, therefore they were early endosomes. After 30-45 minutes,
      the ligand and its receptor no longer colocalized. Fluo-NT was first found in rab
      7-positive late endosomes and later in a nonacidic juxtanuclear compartment
      identified as the Trans-Golgi Network (TGN) by virtue of its staining for
      syntaxin 6. This juxtanuclear compartment also stained positively for rab 7 and
      for the TGN/pericentriolar recycling endosome marker rab 11, suggesting that the
      ligand could have been recruited to the TGN from either late or recycling
      endosomes. By that time, internalized receptors were detected in Lamp-1
      immunoreactive lysosomes. These results demonstrate that neurotensin/NT1 receptor
      complexes follow a recycling cycle that is unique among the G protein-coupled
      receptors studied to date, and provide the first evidence for the targeting of a
      nonendogenous protein from endosomes to the TGN.

PMID- 10934037
TI  - Intracellular distribution and mobilization of unesterified cholesterol in
      adipocytes: triglyceride droplets are surrounded by cholesterol-rich ER-like
      surface layer structures.
AB  - In addition to their central role in triglyceride storage, fat cells are a
      primary depot of unesterified cholesterol (FC) in the body. In comparison,
      peripheral cells contain very little FC. This difference in adipocytes versus
      peripheral tissues is inconsistent with the current theory of cholesterol
      homeostasis. Attempting to resolve this discrepancy, we examined intracellular
      storage sites of FC in murine 3T3-F442A adipocytes. Using the cholesterol-binding
      antibiotic, filipin, in combination with high resolution fluorescence microscopy,
      intense fluorescent staining characteristically decorated the periphery of
      triglyceride droplets (TGD) as well as the plasma membrane (PM) of fat cells.
      Filipin-staining was not visible inside the lipid droplets. Purification of TGD
      by subcellular fractionation demonstrated that the rise in total FC content of
      adipocytes upon differentiation was attributable to an increase in TGD-FC, which
      contributed up to one third of the total cellular FC. The protein component of
      purified TGD from cultured adipocytes as well as from murine adipocytes obtained
      from fresh tissues contained the lumenal endoplasmic reticulum (ER)
      immunoglobulin binding protein (BiP) and the integral ER membrane protein
      calnexin. Efflux experiments using the extracellular FC acceptors (&bgr;)
      cyclodextrin or apolipoprotein A-I demonstrated that TGD-associated FC was
      releasable from TGD. Whereas FC efflux from adipocytes was unaffected in the
      presence of brefeldin A or monensin, the secretion of a control protein,
      lipoprotein lipase, was effectively reduced. In summary, our findings identify
      the TGD surface layer as primary intracellular storage site for FC within
      adipocytes. We suggest that the structural role of ER-resident proteins in this
      adipocyte TGD envelope has been previously neglected. Our findings support the
      suggestion that an ER-like structure, albeit of modified lipid composition,
      constitutes the lipid droplets' surface layer. Finally, the efflux process of FC
      from adipocytes upon extracellular stimulation with (beta)-cyclodextrin provides
      evidence for an energy-dependent intracellular trafficking route between the TGD
      FC pool and the PM-FC sites which is distinct from the secretory pathway of
      proteins.

PMID- 10934038
TI  - The RING finger protein SNURF modulates nuclear trafficking of the androgen
      receptor.
AB  - The androgen receptor (AR) is a transcription factor that mediates androgen
      action. We have used the green fluorescent protein (GFP) technique to investigate
      dynamics of nuclear trafficking of human AR in living cells. In the absence of
      ligand, the GFP-AR fusion protein is distributed between cytoplasm and nuclei.
      Androgen exposure leads to a rapid and complete import of GFP-AR to nuclei of CV
      1 cells (>=90% nuclear in 30 minutes), whereas a pure antiandrogen, Casodex,
      elicits a slower (<40% nuclear in 30 minutes) and incomplete transfer. Unliganded
      ARs with mutations in the basic amino acids of the bipartite nuclear localization
      signal (NLS) within the second zinc finger and the hinge region are predominantly
      cytoplasmic and their androgen-dependent nuclear import is severely compromised
      ((3/4)20% nuclear in 30 minutes). Interestingly, substitutions of the Leu
      residues flanking the bipartite NLS lead to inefficient nuclear transfer in
      response to androgen ((3/4)20% nuclear in 30 minutes). The ligand-binding domain
      of AR, which represses bipartite NLS activity, contains an agonist-specific NLS.
      The small nuclear RING finger protein SNURF, which interacts with AR through a
      region overlapping with the bipartite NLS, facilitates AR import to nuclei and
      retards its export on hormone withdrawal. More AR is associated with the nuclear
      matrix in the presence than absence of coexpressed SNURF. We suggest that the
      SNURF-mediated tethering of AR in nuclei represents a novel mechanism for
      activating steroid receptor functions.

PMID- 10934039
TI  - Nerve growth factor stimulates coupling of beta1 integrin to distinct transport
      mechanisms in the filopodia of growth cones.
AB  - The cycling of membrane receptors for substrate-bound proteins via their
      interaction with the actin cytoskeleton at the leading edge of growth cones and
      other motile cells is important for neurite outgrowth and cell migration.
      Receptor delivered to the leading edge binds to its ligand, which induces
      coupling of the receptor to a rearward flowing network of actin filaments. This
      coupling is thought to facilitate advance. We show here that a soluble growth
      factor stimulates this cycling. We have used single particle tracking to monitor
      the effects of nerve growth factor (NGF) on the movements of beta1 integrin in
      the plane of the plasma membrane of the filopodia of growth cones. Beta1 integrin
      was visualized by its binding of 0.2 microm beads coated with a monoclonal Ab
      directed against an extracellular epitope distant from the binding site for
      extracellular matrix ligands. The beads were observed by video microscopy. Beads
      coated with a low concentration of antibody, and therefore bound to unliganded
      receptor with little cross-linking, showed an increase in both diffusion and
      directed forward transport in response to NGF. Transport had a net velocity of 37
      microm/minute and was characterized by brief periods of sustained forward
      excursions with a velocity of 75-150 microm/minute. There was a 2-fold increase
      in the number of beads accumulated at the tips of filopodia after 10 minutes,
      indicating that NGF enhanced the delivery of beta1 integrin to the periphery.
      Forward transport was dependent on an intact actin cytoskeleton and myosin
      ATPase, since treatment with cytochalasin D or the myosin ATPase inhibitor
      butanedione monoxime inhibited the transport but not the diffusion of receptors.
      NGF also greatly increased the steady rearward migration of beads coated with a
      high density of (&bgr;)1 integrin antibody, indicating that coupling of cross
      linked receptor to the retrograde flow of actin is also enhanced. The rate of the
      retrograde flow of actin was unaffected by NGF. These studies show that a soluble
      factor can stimulate the coupling of a receptor for substrate-bound factor to two
      actomyosin-based transport mechanisms and thus facilitate the response of the
      growth cone to the substrate-bound factor by increasing cycling of the receptor
      at the periphery.

PMID- 10934040
TI  - Microtubule minus-end anchorage at centrosomal and non-centrosomal sites: the
      role of ninein.
AB  - The novel concept of a centrosomal anchoring complex, which is distinct from the
      gamma-tubulin nucleating complex, has previously been proposed following studies
      on cochlear epithelial cells. In this investigation we present evidence from two
      different cell systems which suggests that the centrosomal protein ninein is a
      strong candidate for the proposed anchoring complex. Ninein has recently been
      observed in cultured fibroblast cells to localise primarily to the post-mitotic
      mother centriole, which is the focus for a classic radial microtubule array. We
      show here by immunoelectron microscopical analyses of centrosomes from mouse L929
      cells that ninein concentrates at the appendages surrounding the mother centriole
      and at the microtubule minus-ends. We further show that localisation of ninein in
      the cochlear supporting epithelial cells, where the vast majority of the
      microtubule minus-ends are associated with apical non-centrosomal sites, suggests
      that it is not directly involved in microtubule nucleation. Ninein seems to play
      an important role in the positioning and anchorage of the microtubule minus-ends
      in these epithelial cells. Evidence is presented which suggests that ninein is
      released from the centrosome, translocated with the microtubules, and is
      responsible for the anchorage of microtubule minus-ends to the apical sites. We
      propose that ninein is a non-nucleating microtubule minus-end associated protein
      which may have a dual role as a minus-end capping and anchoring protein.

PMID- 10934041
TI  - Activation of protein kinase Calpha inhibits growth of pancreatic cancer cells
      via p21(cip)-mediated G(1) arrest.
AB  - We have analyzed human pancreatic cancer cells to explore the growth regulatory
      function of protein kinase C (PKC)alpha. PKCalpha subcellular redistribution,
      activation kinetics and downregulation were examined in detail and correlated to
      immediate and delayed effects on cell-cycle regulatory pathways. TPA treatment
      resulted in transient PKC(&agr;) activation accompanied by translocation of the
      enzyme into membrane and nuclear compartments, and was followed by subsequent
      downregulation. TPA-induced inhibition of DNA synthesis was prevented by a PKC
      antagonist and was reproduced by microinjection of recombinant PKCalpha,
      indicating that activation of this isoenzyme was required and sufficient for
      growth inhibitory effects. PKC(&agr;) activation arrested cells in the G(1) phase
      of the cell cycle as a consequence of selective inhibition of cyclin dependent
      kinase (CDK)2 activity with concomitant hypophosphorylation of Rb. The inhibition
      of CDK2 activity resulted from induction of p21(cip1) cyclin-dependent kinase
      inhibitors. Levels of p21(cip1) remained elevated and CDK2 activity repressed in
      spite of PKCalpha downregulation, indicating that downstream effectors of
      PKCalpha are the primary determinants for the duration of PKC-mediated growth
      inhibition. The PKCalpha-induced block in cell proliferation persisted even
      though cells were kept in the presence of growth factors, suggesting that
      induction of PKCalpha results in a permanent withdrawal of pancreatic cancer
      cells from the cell cycle.

PMID- 10934043
TI  - alpha3beta1 and alpha6beta4 integrin receptors for laminin-5 are not essential
      for epidermal morphogenesis and homeostasis during skin development.
AB  - Continuous regeneration and homeostasis of the stratified epidermis requires
      coordinated regulation of cell proliferation, cell differentiation, and cell
      survival. Integrin-mediated cell adhesion to the extracellular matrix has
      important roles in regulating each of these processes. Integrins alpha3beta1 and
      alpha6beta4 are both receptors on epidermal keratinocytes for the basement
      membrane protein laminin-5, the major ligand for epidermal adhesion in mature
      skin. Ablation in mice of either alpha3beta1 or alpha6beta4, through null
      mutation of the gene encoding the alpha3, alpha6, or beta4 integrin subunit,
      results in epidermal blistering of varying severity. Our previous studies showed
      that, despite blistering, differentiation and stratification of the epidermis
      appeared essentially normal in mice that lacked either alpha3beta1 or
      alpha6beta4. However, these studies did not definitively address the specific
      developmental importance of each integrin, since they may have overlapping and/or
      compensatory functions. Given the individual importance of alpha3beta1 or
      alpha6beta4 in maintaining the dermo-epidermal junction in mature skin, we sought
      to determine the importance of these integrins for embryonic skin development and
      epidermal morphogenesis. In the current study, we analyzed skin development in
      mutant embryos that completely lack both integrins alpha3beta1 and alpha6beta4.
      Although alpha3beta1/alpha6beta4-deficient embryos displayed epidermal blistering
      by stage E15.5 of development, they also retained regions of extensive epidermal
      adhesion to the basement membrane through stage E16.5, indicating alternative
      adhesion mechanisms. Apoptosis was induced in detached epidermis of
      alpha3beta1/alpha6beta4-deficient embryos, exemplifying vividly the importance of
      epithelial attachment to the basement membrane for cell survival. However,
      apoptotic cells were completely absent from attached epidermis of
      alpha3beta1/alpha6beta4-deficient embryos, showing that epithelial adhesion that
      occurred independently of alpha3beta1 and alpha6beta4 also protected cells from
      apoptosis. Remarkably, in the absence of the known laminin-5 binding integrins
      (alpha3beta1, alpha6beta4, and alpha6beta1), keratinocytes retained the capacity
      to proliferate in the epidermis, and epidermal stratification and skin
      morphogenesis appeared normal prior to blister formation. These findings show
      that while alpha3beta1 and alpha6beta4 are both required for integrity of the
      dermo-epidermal junction, neither one is essential for epidermal morphogenesis
      during skin development.

PMID- 10934042
TI  - Cyclic AMP and LDL trigger a rapid enhancement in gap junction assembly through a
      stimulation of connexin trafficking.
AB  - Given the rapid turnover of connexin proteins, gap junction (GJ) assembly
      represents an important means of regulating the extent of GJ communication
      between cells. This report describes an increase in the level of GJ assembly
      within one hour following treatment with cAMP-elevating reagents or low density
      lipoprotein (LDL). Dye transfer methods and freeze-fracture with electron
      microscopy were used to assay junctional permeability and structure,
      respectively, subsequent to the dissociation, recovery and reaggregation of
      Novikoff hepatoma cells. Reaggregating cells in the presence of agents that
      increase cAMP levels (8-Br-cAMP, forskolin and IBMX) enhanced both dye transfer
      rates between cells and the extent of GJ formation 2- to 3-fold. These data and
      studies with the protein kinase A inhibitor, H-89, indicate that cAMP signaling
      plays a key role in enhanced assembly. The response to LDL parallels that to cAMP
      and relies on the activity of both adenylyl cyclase and protein kinase A.
      Immunoblot analysis revealed no change in the level of connexin43 (Cx43) or its
      phosphorylation states over a period of 2.5 hours. However, three agents
      (brefeldin A, monensin and nocodazole), that inhibit intracellular membrane
      trafficking by different mechanisms, all blocked the enhanced assembly of GJs
      when triggered by either elevated cAMP or exposure to LDL. Related studies, which
      employed trafficking inhibitors at different stages in GJ assembly, suggested
      that Cx43 trafficking during enhanced assembly is regulated, in part, by cell
      contact. Intracellular sources of Cx43 were characterized by colabeling for
      several markers of cytoplasmic membrane systems. We conclude that an increase in
      GJ assembly: (i) occurs rapidly in the presence of elevated cAMP or LDL, (ii)
      does not require an increase in Cx43 levels or major changes in Cx43
      phosphorylation and (iii) is dependent upon the trafficking of Cx43 from
      intracellular storage sites.

PMID- 10934044
TI  - Pyk2 and FAK differentially regulate progression of the cell cycle.
AB  - We have previously identified FAK and its associated signaling pathways as a
      mediator of cell cycle progression by integrins. In this report, we have analyzed
      the potential role and mechanism of Pyk2, a tyrosine kinase closely related to
      FAK, in cell cycle regulation by using tetracycline-regulated expression system
      as well as chimeric molecules. We have found that induction of Pyk2 inhibited
      G(1) to S phase transition whereas comparable induction of FAK expression
      accelerated it. Furthermore, expression of a chimeric protein containing Pyk2 N
      terminal and kinase domain and FAK C-terminal domain (PFhy1) increased cell cycle
      progression as FAK. Conversely, the complementary chimeric molecule containing
      FAK N-terminal and kinase domain and Pyk2 C-terminal domain (FPhy2) inhibited
      cell cycle progression to an even greater extent than Pyk2. Biochemical analyses
      indicated that Pyk2 and FPhy2 stimulated JNK activation whereas FAK or PFhy1 had
      little effect on it, suggesting that differential activation of JNK by Pyk2 may
      contribute to its inhibition of cell cycle progression. In addition, Pyk2 and
      FPhy2 to a greater extent also inhibited Erk activation in cell adhesion whereas
      FAK and PFhy1 stimulated it, suggesting a role for Erk activation in mediating
      differential regulation of cell cycle by Pyk2 and FAK. A role for Erk and JNK
      pathways in mediating the cell cycle regulation by FAK and Pyk2 was also
      confirmed by using chemical inhibitors for these pathways. Finally, we showed
      that while FAK and PFhy1 were present in focal contacts, Pyk2 and FPhy2 were
      localized in the cytoplasm. Interestingly, both Pyk2 and FPhy2 (to a greater
      extent) were tyrosine phosphorylated and associated with Src and Fyn. This
      suggested that they may inhibit Erk activation in an analogous manner as the
      mislocalized FAK mutant (&Dgr;)C14 described previously by competing with
      endogenous FAK for binding signaling molecules such as Src and Fyn. This model is
      further supported by an inhibition of endogenous FAK association with active Src
      by Pyk2 and FPhy2 and a partial rescue by FAK of Pyk2-mediated cell cycle
      inhibition.

PMID- 10934045
TI  - Involvement of Iba1 in membrane ruffling and phagocytosis of
      macrophages/microglia.
AB  - Ionized calcium binding adaptor molecule 1, Iba1, is an EF hand calcium binding
      protein whose expression is restricted to macrophages/microglia. In this study,
      Iba1 was shown to colocalize with F-actin in membrane ruffles induced by
      macrophage colony-stimulating factor and in phagocytic cups formed during zymosan
      phagocytosis. Expression of mutant Iba1 carrying either N- or C-terminal
      deletions or carrying a substitution in the calcium binding domain, suppressed
      the membrane ruffling and the phagocytosis. These results indicate that Iba1 is a
      key molecule in membrane ruffling and the phagocytosis of macrophages/microglia.
      Furthermore, Iba1 colocalized with a small GTPase Rac in the membrane ruffles and
      the phagocytic cups. The Iba1 mutants also suppressed membrane ruffling induced
      by dominant active Rac1V12, but do not affect microspikes by Cdc42V12 and stress
      fibers by RhoAV14. These observations suggest that Iba1 is involved in Rac and
      calcium signaling pathways.

PMID- 10934046
TI  - Activation-induced nuclear translocation of RING3.
AB  - RING3 is a novel protein kinase linked to human leukaemia. Its Drosophila
      homologue female sterile homeotic is a developmental regulator that interacts
      genetically with trithorax, a human homologue of which is also associated with
      leukaemia. The RING3 structure contains two mutually related bromodomains that
      probably assist in the remodelling of chromatin and thereby affect transcription.
      Consistent with this hypothesis, a RING3-like protein has been identified in the
      mouse Mediator complex, where it is associated with transcription factors. We
      show that, whilst RING3 is constitutively localised to the nucleus of
      exponentially growing HeLa cells, it is delocalised throughout serum-starved
      fibroblasts. We use immunostaining and confocal microscopy to demonstrate that
      RING3 translocates to the fibroblast nucleus upon serum stimulation. After
      translocation, RING3 participates in nuclear protein complexes that include E2F
      proteins; it transactivates the promoters of several important mammalian cell
      cycle genes that are dependent on E2F, including dihydrofolate reductase, cyclin
      D1, cyclin A and cyclin E. We use site-directed mutagenesis of a putative nuclear
      localisation motif to show that the activation-induced nuclear localisation and
      consequent transcriptional activity of RING3 depends on a monopartite, classical
      nuclear localisation sequence. These observations refine and extend the mechanism
      by which RING3 contributes to E2F-regulated cell cycle progression. Deregulation
      of this mechanism may be leukaemogenic.

PMID- 10934047
TI  - The protease-activated receptor-2 upregulates keratinocyte phagocytosis.
AB  - The protease-activated receptor-2 (PAR-2) belongs to the family of seven
      transmembrane domain receptors, which are activated by the specific enzymatic
      cleavage of their extracellular amino termini. Synthetic peptides corresponding
      to the tethered ligand domain (SLIGRL in mouse, SLIGKV in human) can activate PAR
      2 without the need for receptor cleavage. PAR-2 activation is involved in cell
      growth, differentiation and inflammatory processes, and was shown to affect
      melanin and melanosome ingestion by human keratinocytes. Data presented here
      suggest that PAR-2 activation may regulate human keratinocyte phagocytosis. PAR-2
      activation by trypsin, SLIGRL or SLIGKV increased the ability of keratinocytes to
      ingest fluorescently labeled microspheres or E. coli K-12 bioparticles. This PAR
      2 mediated increase in keratinocyte phagocytic capability correlated with an
      increase in actin polymerization and *-actinin reorganization, cell surface
      morphological changes and increased soluble protease activity. Moreover, addition
      of serine protease inhibitors downmodulated both the constitutive and the PAR-2
      mediated increases in phagocytosis, suggesting that serine proteases mediate this
      functional activity in keratinocytes. PAR-2 involvement in keratinocyte
      phagocytosis is a novel function for this receptor.

PMID- 10934049
TI  - Translocation of protein tyrosine phosphatase Pez/PTPD2/PTP36 to the nucleus is
      associated with induction of cell proliferation.
AB  - Pez is a non-transmembrane tyrosine phosphatase with homology to the FERM (4.1,
      ezrin, radixin, moesin) family of proteins. The subcellular localisation of Pez
      in endothelial cells was found to be regulated by cell density and serum
      concentration. In confluent monolayers Pez was cytoplasmic, but in cells cultured
      at low density Pez was nuclear, suggesting that it is a nuclear protein in
      proliferating cells. This notion is supported by the loss of nuclear Pez when
      cells are serum-starved to induce quiescence, and the rapid return of Pez to the
      nucleus upon refeeding with serum to induce proliferation. Vascular endothelial
      cells normally exist as a quiescent confluent monolayer but become proliferative
      during angiogenesis or upon vascular injury. Using a 'wound' assay to mimic these
      events in vitro, Pez was found to be nuclear in the cells that had migrated and
      were proliferative at the 'wound' edge. TGFbeta, which inhibits cell
      proliferation but not migration, inhibited the translocation of Pez to the
      nucleus in the cells at the 'wound' edge, further strengthening the argument that
      Pez plays a role in the nucleus during cell proliferation. Together, the data
      presented indicate that Pez is a nuclear tyrosine phosphatase that may play a
      role in cell proliferation.

PMID- 10934048
TI  - Drosophila D-titin is required for myoblast fusion and skeletal muscle striation.
AB  - An ethylmethane sulfonate (EMS) mutagenesis of Drosophila melanogaster aimed at
      discovering novel genes essential for neuromuscular development identified six
      embryonic lethal alleles of one genetic locus on the third chromosome at 62C. Two
      additional lethal P element insertion lines, l(3)S02001 and l(3)j1D7, failed to
      complement each other and each of the six EMS alleles. Analysis of genomic
      sequence bracketing the two insertion sites predicted a protein of 16,215 amino
      acid residues, encoded by a 70 kb genomic region. This sequence includes the
      recently characterized kettin, and includes all known partial D-Titin sequences.
      We call the genetic locus, which encodes both D-Titin and kettin, D-Titin. D
      Titin has 53 repeats of the immunoglobulin C2 domain, 6 repeats of the
      fibronectin type III domain and two large PEVK domains. Kettin appears to be the
      NH2-terminal one third of D-Titin, presumably expressed via alternative splicing.
      Phenotype assays on the allelic series of D-Titin mutants demonstrated that D
      Titin plays an essential role in muscle development. First, D-Titin has an
      unsuspected function in myoblast fusion during myogenesis and, second, D-Titin
      later serves to organize myofilaments into the highly ordered arrays underlying
      skeletal muscle striation. We propose that D-Titin is instrumental in the
      development of the two defining features of striated muscle: the formation of
      multi-nucleate syncitia and the organization of actin-myosin filaments into
      striated arrays.

PMID- 10934050
TI  - Airway resistance.

PMID- 10934051
TI  - Thrombocytopenic disorders in critically ill patients.

PMID- 10934052
TI  - Exposure to diesel exhaust aggravates nasal allergic reaction in guinea pigs.
AB  - Diesel exhaust particulates (DEP) () and exposure to diesel exhaust (DE) induce
      nasal mucosal hyperresponsiveness to histamine. Therefore, in the present study,
      we investigated whether or not exposing guinea pigs to DE aggravates the nasal
      allergic reaction induced by repeated nasal administration of ovalbumin (OVA).
      Guinea pigs were exposed to filtered air or to DE (DE containing 0.3 or 1.0
      mg/m(3) of DEP) for 5 wk. During exposure to filtered air or to DE, guinea pigs
      were administered 1% of OVA in saline into the nasal cavities once a week.
      Sneezes were counted and nasal secretions were measured as indices of sneezing
      responses and rhinorrhea for 20 min after OVA administration. Titers of specific
      anti-OVA-IgG and anti-OVA-IgE and the number of eosinophils infiltrated into both
      nasal epithelium and subepithelium were measured at the end of the exposure to
      DE. Exposure to DE enhanced the number of sneezes and the amount of nasal
      secretions induced by OVA. Titers of specific anti-OVA-IgG and anti-OVA-IgE also
      significantly increased in DE-exposed animals. Exposure to DE also augmented the
      number of eosinophils that infiltrated both the nasal epithelium and the
      subepithelium induced by OVA. These results suggest that exposure to DE enhances
      the nasal allergic reaction induced by repeated antigen administration in guinea
      pigs.

PMID- 10934053
TI  - Deformation-induced injury of alveolar epithelial cells. Effect of frequency,
      duration, and amplitude.
AB  - The onset of ventilator-induced lung injury (VILI) is linked to a number of
      possible mechanisms. To isolate the possible role of alveolar epithelial
      deformation in the development of VILI, we have developed an in vitro system in
      which changes in alveolar epithelial cell viability can be measured after
      exposure to tightly controlled and physiologically relevant deformations. We
      report here a study of the relative effect of deformation frequency, duration,
      and amplitude on cell viability. We exposed rat primary alveolar epithelial cells
      to a variety of biaxial stretch protocols, and assessed deformation-induced cell
      injury quantitatively, using a fluorescent cell viability assay. Deformation
      induced injury was found to depend on repetitive stretching, with cyclic
      deformations significantly more damaging than tonically held deformations. In
      cyclically deformed cells, injury occurred rapidly, with the majority of cell
      death occurring during the first 5 min of deformation. Deformation-induced injury
      was increased with the frequency of sustained cyclic deformations, but was not
      dependent on the deformation rate during a single stretch. Reducing the amplitude
      of cell deformations by superimposing small cyclic deformations on a tonic
      deformation significantly reduced cell death as compared with large-amplitude
      deformations with the same peak deformation.

PMID- 10934054
TI  - Reverse-thrust ventilation in hypercapnic patients with acute respiratory
      distress syndrome. Acute physiological effects.
AB  - Techniques of tracheal gas insufflation (TGI) have been shown to enhance CO(2)
      clearance efficiency in mechanically ventilated patients with acute respiratory
      distress syndrome (ARDS). Clinical studies have explored the effects of such
      techniques only at moderate intratracheal gas flow rates, with TGI superimposed
      to mechanical ventilation in a continuous fashion, or synchronized to the
      expiratory phase of the duty cycle. We examined the effects of intratracheal
      pulmonary ventilation (ITPV), delivering the entire tidal volume (VT) in the
      proximity of the tracheal carina, with all the gas flow supplied continuously
      through a reverse-thrust catheter (RTC). A potential limitation in the
      application of TGI is dynamic hyperinflation. Therefore, in a subgroup of
      patients, we also evaluated the effects of ITPV on end-expiratory lung volume
      (EELV) by respiratory inductive plethysmography (RIP). Eleven patients with ARDS
      under volume-cycled mechanical ventilation were subsequently switched to ITPV at
      the same baseline respiratory rate, I:E ratio, and VT. At the same minute volume,
      Pa(CO(2)) decreased from 70 +/- 12.3 to 59 +/- 9.5 mm Hg, with a percent
      reduction of 15 +/- 4% (range from 10 to 20%). The CO(2) decrease was greater in
      patients with higher baseline Pa(CO(2)) levels (DeltaPa(CO(2)) = 0.29 x Pa(CO(2))
      - 9.48, r = 0.95). During transition from mechanical ventilation to ITPV,
      tracheal positive end-expiratory pressure (PEEP(tr)) decreased with a
      correspondent decrease in EELV. Both were restored by increasing the PEEP at the
      ventilator by 3.6 +/- 2.0 cm H(2)O. These data suggest that in patients with ARDS
      ITPV effectively reduces dead space ventilation and the employment of the RTC may
      limit or avoid dynamic hyperinflation.

PMID- 10934055
TI  - Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic
      obstructive pulmonary disease.
AB  - Ethane is a product of lipid peroxidation and can be measured in the exhaled air
      as an index of oxidative stress. Oxidant/antioxidant imbalance is important in
      the pathogenesis of chronic obstructive pulmonary disease (COPD). Therefore, we
      measured exhaled ethane in 22 patients with COPD (mean age +/- SEM, 59 +/- 8 yr;
      19 male) and compared it with other noninvasive markers of oxidative stress and
      inflammation such as carbon monoxide (CO), measured electrochemically, and nitric
      oxide (NO), measured by chemiluminescence. Exhaled ethane was collected during a
      flow and pressure-controlled exhalation into a reservoir, discarding dead space
      air contaminated with ambient air. A sample of the collected expired air was
      analyzed by chromatography. Compared with normal subjects (n = 14; eight men;
      age, 33 +/- 2.8 yr), patients with COPD not on steroid treatment (n = 12; FEV(1),
      58 +/- 6%) had elevated levels of exhaled ethane (2.77 +/- 0.25 and 0.88 +/- 0.09
      ppb, respectively, p < 0.05), CO (5.96 +/- 0.50 and 2.8 +/- 0.25 ppm, p < 0.05)
      and NO (11.86 +/- 0.53 and 6.77 +/- 0.50 ppb, p < 0.05) levels. Ethane was
      correlated to FEV(1) (r = -0.67, p < 0.05). Patients receiving steroid treatment
      (n = 10; FEV(1), 56 +/- 2%) had lower levels of ethane (0.48 +/- 0.05 ppb) than
      did steroid-treated patients, whereas CO (5.99 +/- 0.63 ppm) and NO (9.11 +/-
      0.53 ppb) levels were similar in the two treatment groups. Exhaled ethane is
      elevated, correlates with FEV(1), and is significantly lower in patients treated
      with steroids, so it may be complementary to the use of NO and CO in assessing
      and monitoring oxidative stress in COPD.

PMID- 10934056
TI  - Right ventricular function in respiratory distress syndrome and subsequent
      partial liquid ventilation. Homeometric autoregulation in the right ventricle of
      the newborn animal.
AB  - Infant respiratory distress syndrome (IRDS) and subsequent partial liquid
      ventilation (PLV) cause increased pulmonary vascular resistance, thus raising
      afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right
      (RV) and left ventricular (LV) contractility and systolic pump function were
      assessed using indices derived from RV and LV pressure-volume relations, obtained
      by micromanometric and conductance catheters during transient inferior vena cava
      occlusion. Pulmonary function deteriorated during IRDS with a significant
      decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen
      (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant
      increase and pulmonary vascular resistance showed a substantial though not
      significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic
      volume (EDV) did not change. RV contractility showed a significant increase
      during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES))
      increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload
      corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did
      not change significantly. LV pump function and contractility were unchanged.
      During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular
      resistance remained high; indices for RV contractility showed a sustained
      significant increase compared with baseline conditions whereas indices for LV
      pump function and contractility remained unchanged. These results show that the
      right ventricle of the newborn heart, in the face of increased pulmonary vascular
      resistance, is able to maintain cardiac output through homeometric
      autoregulation.

PMID- 10934057
TI  - Critical roles for interleukin-4 and interleukin-5 during respiratory syncytial
      virus infection in the development of airway hyperresponsiveness after airway
      sensitization.
AB  - In mice, respiratory syncytial virus (RSV) infection can enhance the consequences
      of allergic airway sensitization, resulting in lung eosinophilia and the
      development of airway hyperresponsiveness (AHR) to inhaled methacholine (MCh). To
      delineate a role for interleukin-5 (IL-5), interleukin-4 (IL-4), and interferon
      gamma (IFN-gamma) in mediating the effects of RSV infection on subsequent
      allergic sensitization, we treated BALB/c mice with anti-IL-5 during acute RSV
      infection but not during subsequent exposure to ovalbumin (OVA). IL-5-deficient
      and IL-4-deficient mice were also treated with IL-5 either during acute RSV
      infection or during the sensitization period. Airway responsiveness to inhaled
      MCh was assessed and numbers of lung eosinophils were monitored. Anti-IL-5
      treatment during RSV infection reduced AHR and lung eosinophilia after subsequent
      exposure to allergen. In IL-5-deficient or IL-4-deficient mice lung eosinophilia
      and AHR after RSV infection and allergen exposure were also markedly reduced. IL
      5 administration during RSV infection restored the responses to allergen in both
      IL-5- and IL-4-deficient mice. However, IL-5 administration only during
      sensitization restored these responses in IL-4-deficient but not in IL-5
      deficient animals. IFN-gamma-deficient mice developed AHR and some lung
      eosinophilia after allergen exposure alone and when RSV infection preceded
      allergen, these responses were enhanced. We conclude that both IL-5, particularly
      during acute infection, and IL-4 are critical in mediating the effects of RSV
      infection on allergic airway sensitization, resulting in the development of AHR
      and lung eosinophilia.

PMID- 10934058
TI  - Tracheal gas insufflation. Limits of efficacy in adults with acute respiratory
      distress syndrome.
AB  - In mechanically ventilated adults with acute respiratory distress syndrome
      (ARDS), peak airway pressures (Paw(peak)) above 35 cm H(2)O may increase the risk
      of barotrauma or volutrauma. Tracheal gas insufflation (TGI), an adjunctive
      ventilatory technique, may facilitate a reduction in set inspiratory pressure in
      these patients, and thereby in the tidal volume (VT) and Paw(peak) used in their
      ventilation, without a consequent increase in arterial carbon dioxide tension
      (PaCO(2)). The purpose of this study was to: (1) assess the limits of efficacy of
      continuous TGI at two levels of decreased mechanical ventilatory support; and (2)
      determine an appropriate time interval after initiation of TGI at which to
      evaluate response. We prospectively studied eight adults with ARDS and increased
      airway pressures (40.2 +/- 2.7 cm H(2)O) who were managed with pressure-control
      ventilation (PCV). After obtaining baseline ventilatory and hemodynamic measures,
      we initiated TGI at 10 L/min, adjusting ventilator positive-end expiratory
      pressure (PEEP) to maintain baseline VT, and decreased the set inspiratory
      pressure by 5 cm H(2)O. Data were obtained after 30 and 60 min. Set inspiratory
      pressure was then decreased by an additional 5 cm H(2)O (total: 10 cm H(2)O), and
      data were again obtained after 30 min. Baseline (zero TGI) measures were then
      again recorded. Thirty minutes after decreasing the set inspiratory pressure by 5
      cm H(2)O with TGI at 10 L/min, there was a 15% decrease in Paw(peak) and a 16%
      decrease in VT as compared with their baseline values. However, Pa(CO(2))
      remained constant (59 +/- 10 mm Hg versus 57 +/- 6 mm Hg) (p = NS). There was no
      change in Pa(O(2)) or in hemodynamic variables, and no differences between
      variables, at 30 min versus 60 min in seven subjects. The remaining subject did
      not tolerate the reduction in set inspiratory pressure for 60 min. Thirty minutes
      after the set inspiratory pressure was decreased by 10 cm H(2)O with TGI at 10
      L/min, there was a 26% decrease in Paw(peak) and a 26% decrease in VT. However,
      Pa(CO(2)) increased by 19% and Pa(O(2)) decreased by 13%. Six subjects completed
      this phase of the protocol for 30 min, and one subject completed it for 60 min.
      TGI can be used to rapidly facilitate a 5 cm H(2)O reduction in set inspiratory
      pressure without an increase in Pa(CO(2)). The ability to achieve a 5 cm H(2)O
      reduction in set inspiratory pressure without adverse physiologic effects was
      evident within 30 min. Attempts to further reduce set inspiratory pressure were
      not successful.

PMID- 10934060
TI  - Injurious effects of hypocapnic alkalosis in the isolated lung.
AB  - Mechanical ventilation can worsen morbidity and mortality by causing ventilator
      associated lung injury, especially where adverse ventilatory strategies are
      employed. Adverse strategies commonly involve hyperventilation, which frequently
      results in hypocapnia. Although hypocapnia is associated with significant lung
      alterations (e.g., bronchospasm, airway edema), the effects on alveolar-capillary
      permeability are unknown. We investigated whether hypocapnia could cause lung
      injury independent of altering ventilatory strategy. We hypothesized that
      hypocapnia would cause lung injury during prolonged ventilation, and would worsen
      injury following ischemia-reperfusion. We utilized the isolated buffer-perfused
      rabbit lung model. Pilot studies assessed a range of levels of hypocapnic
      alkalosis. Experimental preparations were randomized to control groups (FI(CO(2))
      = 0.06) or groups with hypocapnia (FI(CO(2)) = 0.01). Following prolonged
      ventilation, pulmonary artery pressure, airway pressure, and lung weight were
      unchanged in the control group but were elevated in the group with hypocapnia;
      elevation in microvascular permeability was greater in the hypocapnia versus
      control groups. Injury following ischemia-reperfusion was significantly worse in
      the hypocapnia versus control groups. In a preliminary series, degree of lung
      injury was proportional to the degree of hypocapnic alkalosis. We conclude that
      in the current model (1) hypocapnic alkalosis is directly injurious to the lung
      and (2) hypocapnic alkalosis potentiates ischemia-reperfusion-induced acute lung
      injury.

PMID- 10934059
TI  - Improvements in outcomes of acute respiratory failure for patients with human
      immunodeficiency virus-related Pneumocystis carinii pneumonia.
AB  - In the early 1990s, hospital survival among patients with human immunodeficiency
      virus (HIV)-related Pneumocystis carinii pneumonia (PCP) and respiratory failure
      was poor, approximately 20%. We examined ICU use and outcomes for patients with
      acute respiratory failure from PCP from 1995 to 1997. We conducted a
      retrospective medical record review using a random sample of 71 hospitals in
      seven regions of the United States. Among 1,660 patients with confirmed or
      presumed PCP, 155 (9%) received mechanical ventilation for respiratory failure.
      Factors that predicted use of mechanical ventilation, independent of severity of
      illness on hospital admission, included African-American ethnicity and geographic
      location (p </= 0.002). Hospital survival for patients receiving mechanical
      ventilation was 38% (95% CI 30, 46). Controlling for severity of illness,
      patients who were on PCP prophylaxis prior to developing PCP were less likely to
      survive to hospital discharge (p </= 0.02). There were no significant differences
      in hospital survival regardless of whether patients had received less than or
      more than 5 d of PCP treatment prior to respiratory failure (39 versus 29%; p =
      0.5). In conclusion, from 1995 to 1997, hospital survival after PCP requiring
      mechanical ventilation was approximately 40%. Physicians caring for patients with
      severe HIV-related PCP should be aware of the improvements in outcomes for this
      disease before making recommendations about withholding or withdrawing
      ventilatory support for respiratory failure.

PMID- 10934061
TI  - Upper airway resistance syndrome. Central electroencephalographic power and
      changes in breathing effort.
AB  - Upper airway resistance syndrome (UARS) is defined by excessive daytime
      sleepiness and tiredness, and is associated with increased breathing effort. Its
      polygraphic features involve progressive increases in esophageal pressure (Pes),
      terminated by arousal (AR) as defined by the American Sleep Disorders Association
      (ASDA). With the arousal there is an abrupt decrease in Pes, called Pes reversal.
      However, Pes reversal can be seen without the presence of an AR. We performed
      spectral analysis on electroencephalographic data from a central lead for both AR
      and nonarousal (N-AR) events obtained from 15 UARS patients (eight men and seven
      women). Delta band activity was increased before and surrounding Pes reversal
      regardless of the presence or absence of AR. In the period after Pes reversal,
      alpha, sigma, and beta activity showed a greater increase in AR events than in N
      AR events. The Pes measures were identical leading up to the point of reversal,
      but showed a longer-lasting and significantly greater decrease in respiratory
      effort after an AR. The data indicate that substantial electroencephalographic
      changes can be identified in association with Pes events, even when ARs cannot be
      detected according to standard criteria; however, visually identifiable
      electroencephalographic arousals clearly have a greater impact on ongoing
      inspiratory effort.

PMID- 10934062
TI  - Lung and chest wall mechanics in anesthetized children. Influence of body
      position.
AB  - The mechanical behavior of the lung and chest wall has not been determined in
      preschool children. We therefore obtained static expiratory pressure-volume (P-V)
      curves of the respiratory system, partitioned into lung and chest wall components
      using esophageal (Pes) and airway pressure (Paw) registration in 17 anesthetized
      children (0.2 to 15.5 yr) in the supine and lateral position. From the P-V curves
      the inspiratory capacity (IC), the chest wall elastance (Ecw), and the maximal
      compliance of the respiratory system (Crs) and lungs (C(lung)) were calculated
      and related to growth. At IC (Paw = 30 cm H(2)O), Pes was the same in the two
      positions: 11 +/- 3 cm H(2)O. In contrast, at end-expiration (Paw = 0), Pes was
      close to zero in the lateral position, but markedly positive in the supine
      position (7 +/- 2 cm H(2)O). C(lung) was similar in both positions and increased
      with growth. Thus, C(lung) in the lateral position (ml/cm H(2)O) = 0.0017 x
      length(2.26) (cm), r(2) = 0.90. Crs and IC were approximately 20% greater (p </=
      0.001) in the supine position than in the lateral, and correlated strongly (r(2)
      >/= 0.93) with power functions of length in both positions. Ecw expressed as a
      fraction of total respiratory system elastance (Ecw/Ers) was 33 +/- 12% in the
      lateral position and 12 +/- 16% supine (p < 0.001). We conclude that the
      respiratory mechanics in children correlated closely with body size and showed
      important differences between the supine and lateral positions.

PMID- 10934063
TI  - Outcomes of critically ill patients denied consideration for liver
      transplantation.
AB  - Patients with advanced liver disease (ALD) leading to admission to the ICU are
      often evaluated for possible orthotopic liver transplantation (OLT). Those deemed
      ineligible for listing for OLT must be managed by medical therapy. The number of
      patients not eligible for OLT listing will likely increase given the current
      organ transplant shortage. We performed a retrospective multivariate analysis of
      mortality predictors for patients denied listing for OLT. One hundred and eighty
      three patients denied OLT listing were evaluated over a 3(1)/(2)-yr period,
      beginning in 1994. Overall mortality was 56% for those not listed versus 12% for
      those listed for OLT (p < 0.001). Independent predictors of increased mortality
      among those not listed were APACHE II score (p = 0.001; OR 1.11), sepsis (p =
      0.04; OR 2.41), and the need for mechanical ventilation (p = 0.001; OR 3.71).
      Gastrointestinal (GI) bleeding was associated with decreased mortality (p = 0.02;
      OR 0.44). We conclude that critically ill patients with ALD denied OLT listing
      have substantially higher mortality than those listed for OLT. APACHE II score,
      sepsis, and the need for mechanical ventilation predict increased mortality in
      this group. Conversely, GI bleeding predicts decreased mortality; therefore,
      aggressive resuscitative measures seem merited in these patients.

PMID- 10934064
TI  - Lung function reference values in Chinese children and adolescents in Hong Kong.
      I. Spirometric values and comparison with other populations.
AB  - As part of a comprehensive evaluation of lung function in Hong Kong-born Chinese
      children and adolescents, this study was conducted to determine updated
      prediction equations for spirometry, to evaluate the secular changes of lung
      function during the past decade, and to compare these results with other data
      sets. The results are based on 852 (392 male, 460 female) healthy students, age 7
      to 19 yr, recruited from seven schools in Hong Kong. All were born and lived in
      Hong Kong, nonsmokers, free from past or present symptoms or diseases affecting
      the respiratory tract. A body plethysmograph was used to record lung function
      measurements. Natural logarithmic values of lung volumes and body height were
      used in the final regression model. Prediction equations for FVC, FEV(1), and
      maximal expiratory flow at 50% of the FVC (MEF(50)) for both sexes are presented,
      with standing height as the dependent variable. Compared with Hong Kong data from
      1985, the results show a significant increase in height-corrected FVC and FEV(1)
      in both boys and girls, over the whole height range. Compared with recent data of
      whites, FVC in boys were 8 to 10% lower in the study population, and the
      difference increased to 12% above the 165 cm height ranges, while FVC in Chinese
      girls had similar or only slightly lower predicted values. FEV(1) values showed a
      similar pattern with lesser difference between the two ethnic groups. Compared
      with recent data from Chinese children in Singapore, a similar pattern with
      overall lesser difference of the two populations was present in boys, whereas
      there was no significant difference between girls in the two places. Our findings
      support the conclusion that exogenous factors may contribute significantly to the
      differences in lung function values among ethnic groups and that it is important
      to examine normative values of various populations for secular trends.

PMID- 10934065
TI  - Lung function reference values in Chinese children and adolescents in Hong Kong.
      II. Prediction equations for plethysmographic lung volumes.
AB  - As part of a comprehensive evaluation of lung function in Hong Kong Chinese
      children and adolescents, over a thousand healthy subjects aged 7-19 yr from
      seven schools were recruited for lung function testing that included spirometry
      and, in many cases, lung subdivision measurements. Lung function tests were
      performed using SensorMedics Automated Body Plethysmograph according to published
      standards. Of these, 551 subjects (219 males), aged 8-19 yr, had satisfactory
      lung subdivision indices recorded. Analysis for the values of lung subdivisions
      including total lung capacity (TLC), residual volume (RV), and functional
      residual capacity (FRC) demonstrated that standing height and sitting height were
      the best predictors of lung volumes. After allowing for standing height or
      sitting height in the regression models for lung volumes, age at examination was
      the second best parameter, although its inclusion into the equations contributed
      to less than 1% of explained variance for boys and 3% for girls. These are the
      first reported data in international literature on reference values for lung
      subdivisions in Chinese children and adolescents.

PMID- 10934066
TI  - Maximal and partial expiratory flow rates in a population sample of 10- to 11-yr
      old schoolchildren. Effect of volume history and relation to asthma and maternal
      smoking.
AB  - The effect of volume history on forced expiratory flow rates has been reported to
      differ between patients with asthma and healthy persons, and it has been
      hypothesized that the peripheral airway inflammation of patients with asthma may
      underlie this difference. There are no published data, however, on the
      distribution of such volume history effects or the relation of these effects to
      airways disease in children. We obtained combined partial and maximal forced
      expiratory flow-volume curves on 1,834 children, age 10-11 yr, in eight
      communities in the United States and Canada. The effect of a deep inhalation on
      forced expiratory flow rates at low lung volumes was quantitated by the ratio of
      V (30) during a maximal expiratory maneuver (V (30M)) to V (30) during a partial
      expiratory maneuver (V (30P)). The V (30M)/V (30P) ratio was slightly higher
      among girls than boys (1.26 versus 1.18, p = 0.0001) indicating that a deep
      inhalation increased V (30) slightly more among girls than among boys. The V
      (30M)/V (30P) ratio was related to neither history of asthma nor to maternal
      smoking. In contrast, most spirometric indices from either the maximal or the
      partial expiratory flow-volume curve were lower in association with a history of
      asthma or a report of maternal smoking. The ratio of FEF(25-75)/FVC was
      particularly consistent as a measurement that discriminated both of these effects
      in boys and girls. These results suggest that the measurement of volume history
      effects offers no benefits for epidemiological studies of childhood respiratory
      disease whereas spirometric indices such as the FEF(25-75)/FVC ratio are quite
      sensitive to the effects of asthma and environmental tobacco smoke exposure on
      the airways.

PMID- 10934067
TI  - Predictors of pain control in patients undergoing flexible bronchoscopy.
AB  - The purpose of this study was to assess the extent to which patients undergoing
      flexible bronchoscopy (FOB) experience pain and to identify patient factors and
      process of care factors that are associated with pain. We conducted a prospective
      cohort study on 481 patients undergoing FOB. Overall control of pain during FOB
      was the primary outcome. The mean age of the patients was 48 yr, 50% were male,
      and 32% required supplemental oxygen prior to FOB. Pain control was excellent in
      36% of patients, but 10% considered it to be fair or poor. Patient factors
      associated with excellent pain control were excellent health (versus poor health,
      OR = 6.25 [95% CI, 2.28-16.67]), more education (college education versus high
      school education, OR = 1.72 [95% CI, 1.05-2.86]), and not having asthma (OR =
      2.86 [95% CI, 1.09-7.14]). Process of care factors associated with excellent pain
      control were not being bothered by scope insertion (versus bothered, OR = 3.65
      [95% CI, 1.99-6.98]), no memory of FOB (versus some memory, OR = 2.33 [95% CI,
      1.24-4.44]), and higher ratings of information about the procedure (per 1-point
      increase on a 12-point scale, OR = 1.57 [95% CI, 1.41-1.78]). This is the first
      large-scale, prospective study to evaluate patient and process of care factors
      that influence pain control during FOB. It demonstrated that there are patient
      characteristics and process of care factors that need to be considered when
      evaluating pain during bronchoscopy. Improved preparation of patients with lower
      education, inferior health status, and asthma may lead to decreased pain during
      FOB. Bronchoscopists may be able to reduce pain during FOB by identifying methods
      to decrease pain on scope insertion, by improving the information provided to
      patients, and by achieving greater levels of amnesia during FOB.

PMID- 10934068
TI  - Production of endogenous nitric oxide in chronic obstructive pulmonary disease
      and patients with cor pulmonale. Correlates with echo-Doppler assessment.
AB  - Exhaled nitric oxide (NO) production in stable chronic obstructive pulmonary
      disease (COPD) has been loosely related to the severity of illness, being
      significantly reduced in the most severe cases. Pulmonary hypertension is
      associated with lower NO output from the lung. In this study expired NO was
      measured in patients with severe stable COPD with or without cor pulmonale (CP).
      Echocardiographic estimates of right heart function, lung function, diffusion
      capacity, respiratory muscle strength, and arterial blood gases were obtained in
      34 consecutive patients with stable COPD (mean age, 68 +/- 7 yr). Expired NO was
      measured by chemiluminiscence to obtain fractional exhaled concentrations at peak
      (FENOp) and at plateau (FENOpl) points of the single-breath curve and resting NO
      output (V NO). All measurements of expired NO output, FENOp, FENOpl and V NO
      showed a negative correlation with both systolic pulmonary artery pressure (Pspa)
      (r = -0.51, -0.63, and -0.63, respectively, p < 0.01 for all) and right ventricle
      wall dimension (r = -0.41, -0.59, and -0.43, respectively, p < 0.05 for all), but
      not with any measurement of lung function. When the patients were divided
      according to the Pspa using a cutoff limit of 35 mm Hg, those subjects with CP
      showed lower FENOp (13.2 +/- 4.0 versus 36.7 +/- 30.8 ppb, p < 0.05), FENOpl (5.7
      +/- 1.9 versus 8.9 +/- 4.7 ppb, p < 0.05), and V NO (69. 2 +/- 5.6 versus 107.6
      +/- 14.6 nl/ min, p = 0.02) than did those with a normal resting Pspa. NO
      production from the airways was significantly lower and inversely related to
      development of CP in patients with severe COPD. Impaired endothelial release may
      account for the reduced levels of expired NO.

PMID- 10934069
TI  - Quality of dyspnea in bronchoconstriction differs from external resistive loads.
AB  - To test the hypothesis that patients perceive the same quality of dyspnea during
      mild bronchoconstriction and external resistive loads, we studied subjects with
      asthma under two conditions: (1) during methacholine bronchoprovocation to mimic
      the bronchospasm of mild asthma and (2) while breathing on a circuit to which was
      added a range of external resistors to mimic the mechanical load of mild asthma.
      During each of these stimuli, respiratory variables, overall dyspnea intensity on
      a modified Borg scale, and the qualitative descriptors of breathlessness from a
      19-item questionnaire were assessed. The "chest tightness" and "constriction"
      responses were significantly more frequent in the methacholine trials as compared
      with the external load trials (p < 0.0001). The "chest tightness" or
      "constriction" response was chosen during 92% of the 26 trials of methacholine
      bronchoconstriction compared with 3% of the 72 trials of breathing against the
      external resistors. Changes in functional residual capacity were not
      significantly different between the two conditions. We conclude that in mild
      asthma, the sensation of chest tightness is distinct from the sensation of work
      and effort and is not attributable to the mechanical load imposed on the
      respiratory system.

PMID- 10934070
TI  - Diaphragm recruitment during nonrespiratory activities.
AB  - We previously found that weight lifters could generate greater inspiratory
      pressures and had more diaphragm mass than control subjects. We postulated that
      the weight-lifting activity itself provided a strength-training stimulus to the
      diaphragm. To evaluate the extent to which the diaphragm is recruited during
      strenuous nonrespiratory activities, we measured transdiaphragmatic pressure
      (Pdi) in six healthy subjects during biceps curls, bench press, power lift, and
      sit-ups. Each maneuver was performed with and without added weight (control), and
      with and without an abdominal binder. The weighted maneuvers were performed
      either during inspiration or expiration. Maximal static transdiaphragmatic
      pressure (Pdi(max)) was measured during a combined inspiratory and expulsive
      maneuver. Group mean values of Pdi increased during all activities when compared
      with control (57 +/- 24 versus 18 +/- 10 cm H(2)O [mean +/- SD] [p < 0.001]), as
      task intensity increased (98 +/- 14 versus 35 +/- 13 cm H(2)O for high- and low
      intensity activities, respectively) (p < 0.001), and with abdominal binding (75
      +/- 25 versus 59 +/- 25 cm H(2)O) (p < 0.05). Peak levels of Pdi attained during
      the activities were 126 +/- 11 cm H(2)O or 0.65 +/- 0.09 of Pdi(max). Changes in
      gastric pressure accounted for 85 +/- 4% of the increase in Pdi during the
      activities whereas it accounted for only 58 +/- 9% of the rise in Pdi during the
      control activities (p < 0.001). We conclude that during a range of weight-lifting
      activities, the diaphragm is recruited and Pdi is raised to a level that may
      provide a significant strength-training stimulus to the diaphragm.

PMID- 10934071
TI  - Tuberculosis in the homeless. A prospective study.
AB  - We set out to determine tuberculosis incidence and risk factors in the homeless
      population in San Francisco. We also examined the transmission of tuberculosis by
      molecular methods. We followed a cohort of 2,774 of the homeless first seen
      between 1990 and 1994. There were 25 incident cases during the period 1992 to
      1996, or 270 per 100,000 per year (350/100,000 in African Americans, 450/100,000
      in other nonwhites, 60/100,000 in whites). Ten cases were persons with
      seropositive HIV. Independent risk factors for tuberculosis were HIV infection,
      African American or other nonwhite ethnicity, positive tuberculin skin test (TST)
      results, age, and education; 60% of the cases had clustered patterns of
      restriction fragment length polymorphism, thought to represent recent
      transmission of infection with rapid progression to disease. Seventy-seven
      percent of African-American cases were clustered, and 88% of HIV-seropositive
      cases. The high rate of tuberculosis in the homeless was due to recent
      transmission in those HIV-positive and nonwhite. African Americans and other
      nonwhites may be at high risk for infection or rapid progression. Control
      measures in the homeless should include directly observed therapy and incentive
      approaches, treatment of latent tuberculous infection in those HIV-seropositive,
      and screening in hotels and shelters.

PMID- 10934072
TI  - Effect of aminoguanidine on lung fluid filtration after endotoxin in awake sheep.
AB  - It has been suggested that enhanced generation of nitric oxide by inducible
      nitric oxide synthase (iNOS) may contribute to acute lung injury. We hypothesized
      that aminoguanidine (AG), a proposed selective inhibitor of iNOS, would alter
      pulmonary hemodynamics, fluid filtration, and gas exchange after endotoxin in
      chronically instrumented awake sheep. Eighteen sheep were randomly assigned to
      receive either AG (10 mg/kg + 1 mg/kg/h), or NaCl 0.9% intravenously for 4 h,
      beginning 2 h after injection of Escherichia coli endotoxin (1 microgram/kg).
      After endotoxin, pulmonary artery pressure (Ppa), capillary pressure (Pc), and
      vascular resistance index (PVRI) rose concomitantly with six-fold increments in
      lung lymph flow (Q L) and protein clearance (CL). Extravascular lung water (EVLW)
      doubled, as assessed with the thermal dye dilution technique; Pa(O(2)) decreased,
      AaPO(2) and venous admixture (Q S/Q T) increased. After AG, Q L and CL increased
      further by approximately 30%, whereas EVLW remained unchanged, despite an
      additional increase in Pc. Ppa, PVRI, and systemic vascular resistance index
      rose, whereas cardiac index and pulmonary blood volume index declined. In
      addition, Pa(O(2)) rose, and AaPO(2) and Q S/Q T decreased. We conclude that in
      endotoxemic sheep, AG improves gas exchange and increases Q L and CL, whereas
      EVLW remains unchanged in spite of enhanced Pc. Apparently, increased lymphatic
      drainage prevents EVLW from rising after AG.

PMID- 10934073
TI  - Comparison of apnea identified by respiratory inductance plethysmography with
      that detected by end-tidal CO(2) or thermistor. The CHIME Study Group.
AB  - As part of the Collaborative Home Infant Monitoring Evaluation (CHIME) we
      compared apnea identified by a customized home monitor using respiratory
      inductance plethysmography (RIP) with simultaneously recorded polysomnography
      acquired nasal end-tidal CO(2) (PET(CO(2))) and nasal/oral thermistor in 422
      infants during overnight laboratory recordings to determine concordance between
      techniques, sources of disagreement, and capacity of RIP to detect obstructed
      breaths within an apnea. Among 233 episodes of apnea identified by at least one
      method as >/= 16 s, 120 were observed by the CHIME monitor, 219 by PET(CO(2)),
      and 163 by thermistor. The positive predictive value of the CHIME-identified
      apnea was 89.2% (95% CI 83, 95) and 73% (95% CI 65, 81) for PET(CO(2)) and
      thermistor, respectively. However, the sensitivity of the CHIME monitor in
      identifying events detected by the other methods was only approximately 50%.
      Among 87 apnea events identified by all three techniques, no two methods showed
      high agreement in measurement of apnea duration: RIP and PET(CO(2)) (ICC = 0.54),
      RIP and thermistor (ICC = 0.13), PET(CO(2)) and nasal thermistor (ICC = 0.41).
      Among the 179 breaths identified by RIP as obstructed, 79.9% were judged to be
      obstructed on the PET(CO(2)) and 80.4% were judged to be obstructed on the
      thermistor channel. Among 238 breaths identified on PET(CO(2)) as obstructed,
      54.2% were determined to be obstructed by RIP. Among 204 breaths identified on
      thermistor as obstructed, 55. 4% were determined to be obstructed by RIP. Reasons
      for discrepancies in apnea detection among channels included body movement,
      partial airway obstruction, and obstructed breaths. Despite these limitations the
      CHIME monitor provides an opportunity to record physiological data previously
      unavailable in the home.

PMID- 10934074
TI  - Tobramycin solution for inhalation reduces sputum Pseudomonas aeruginosa density
      in bronchiectasis.
AB  - We conducted a placebo-controlled, double-blind, randomized study to evaluate the
      microbiological efficacy and safety of inhaled tobramycin for treatment of
      patients with bronchiectasis and Pseudomonas aeruginosa. Patients were randomly
      assigned to receive either tobramycin solution for inhalation (TSI) (n = 37) or
      placebo (n = 37), which was self-administered twice daily for 4 wk and followed
      by 2-wk off-drug. At Week 4, the TSI group had a mean decrease in P. aeruginosa
      density of 4.54 log(10) colony-forming units (cfu)/g sputum compared with no
      change in the placebo group (p < 0.01). At Week 6, P. aeruginosa was eradicated
      in 35% of TSI patients but was detected in all placebo patients. Investigators
      indicated that 62% of TSI patients showed an improved medical condition compared
      with 38% of placebo patients (odds ratio = 2.7, 95% confidence interval [CI] 1.1
      to 6.9). Tobramycin-resistant P. aeruginosa strains developed in 11% of TSI
      patients and 3% of placebo patients (p = 0.36). The mean percent change in FEV(1)
      percent predicted from Week 0 to Week 4 was similar for the TSI and placebo
      groups (p = 0.41). More TSI-treated patients than placebo patients reported
      increased cough, dyspnea, wheezing, and noncardiac chest pain, but the symptoms
      did not limit therapy. Additional study is warranted to further evaluate TSI in
      bronchiectasis patients.

PMID- 10934076
TI  - Symptom perception during acute bronchoconstriction.
AB  - The hypothesis underlying the present study was that some of the variability in
      symptom intensity seen during acute bronchoconstriction may result from varying
      intensities of several stimuli yielding several sensations that can be identified
      by specific descriptive expressions (symptoms). A total of 232 subjects inhaled
      methacholine in doubling concentrations to a 20% decrease in FEV(1), or 64 mg/ml.
      The study identified the prevalence of dyspnea, nonspecific discomfort associated
      with the act of breathing, and 10 specific symptom expressions. Each symptom
      intensity was rated in Borg scale units. The contribution of the specific
      symptoms to the intensity of dyspnea is illustrated in the following equation (r
      = 0. 84): Dyspnea = 0.44 + 0.19 Difficult breathing + 0.41 Chest tightness + 0.20
      Breathlessness + 0.14 Labored breathing + 0.11 Chest pain. Dyspnea was more
      intense with broncho-constriction, baseline pulmonary impairment, weight, and sex
      (being female). Dyspnea was less intense with age (being older) and as airway
      responsiveness to methacholine increased (p < 0.05 for all factors). Chest
      tightness and chest pain were at polar extremes on the discrimination scale,
      i.e., easily discriminated; chest tightness, difficult and labored breathing were
      not easily discriminated.

PMID- 10934075
TI  - Mycobacterial lipoarabinomannan induces an inflammatory response in the mouse
      lung. A role for interleukin-1.
AB  - Lipoarabinomannan (LAM), a cell wall component of Mycobacterium tuberculosis,
      induces the production of cytokines and chemokines in vitro. Interleukin-1 (IL-1)
      contributes to granuloma formation in tuberculosis (TB), and exerts effects via
      the IL-1 receptor type I (IL-1R). To determine the effects of LAM in the
      pulmonary compartment in vivo and to establish the role of endogenous IL-1
      herein, normal and IL-1R deficient ((-/-)) mice were intranasally inoculated with
      LAM (50 microgram). In normal mice, LAM resulted in a neutrophilic cell influx
      into the bronchoalveolar lavage fluid (BALF). LAM also induced increases in the
      lung concentrations of macrophage inflammatory protein-2 (MIP-2), keratinocyte
      (KC), tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, and IL-1beta. IL-1R(-/
      ) mice had less influx of granulocytes in their BALF than wild-type mice. Also,
      lung TNF-alpha levels were lower in IL-1R(-/-) mice. LAM may be an important
      stimulator of innate immunity in infection with M. tuberculosis via mechanisms
      that involve endogenous IL-1 activity.

PMID- 10934077
TI  - Determinants of the exercise endurance capacity in patients with chronic
      obstructive pulmonary disease. The power-duration relationship.
AB  - To characterize the determinants of the power-duration (W-t) relationship in
      patients with chronic obstructive pulmonary disease (COPD), we evaluated 8
      nonhypoxemic patients (FEV(1) = 1.27 +/- 0.26 L) and 10 healthy controls. After
      an initial maximum-incremental exercise test on cycle ergometer (peak), the
      subjects underwent four high-intensity constant-load tests to the limit of
      tolerance (t), each on different days. The W-t relationship was found to be
      hyperbolic in both groups. Absolute values of both the critical power asymptote
      (theta(F)) and the curvature constant (W') were lower in patients than in control
      subjects. However, when expressed as percentage of peak work rate theta(F) was
      significantly higher in patients compared with control subjects (81.8 +/- 3.3%
      versus 67.5 +/- 3.7%, respectively, p < 0.01). There were severe reductions in t
      in the patients that were consistently associated with higher breathlessness
      scores and V E/MVV ratios. Interestingly, all patients were able to sustain
      exercise at theta(F) for 20 min despite near-maximum physiological and subjective
      stresses. We conclude that the reductions of both parameters of the hyperbolic W
      t relationship (theta(F) and W') in patients with COPD were due to the
      ventilatory constraints and their sensory consequences. Importantly, theta(F)
      separated a "sustainable" from a "nonsustainable" exercise-intensity domain: this
      parameter consistently occurred closer to peak work rate in patients than the
      healthy control subjects.

PMID- 10934078
TI  - Short-course empiric antibiotic therapy for patients with pulmonary infiltrates
      in the intensive care unit. A proposed solution for indiscriminate antibiotic
      prescription.
AB  - Inappropriate antibiotic use for pulmonary infiltrates is common in the intensive
      care unit (ICU). We sought to devise an approach that would minimize unnecessary
      antibiotic use, recognizing that a gold standard for the diagnosis of nosocomial
      pneumonia does not exist. In a randomized trial, clinical pulmonary infection
      score (CPIS) (Pugin, J., R. Auckenthaler, N. Mili, J. P. Janssens, R. D. Lew, and
      P. M. Suter. Diagnosis of ventilator-associated pneumonia by bacteriologic
      analysis of bronchoscopic and nonbronchoscopic "blind" bronchoalveolar lavage
      fluid. Am. Rev. Respir. Dis. 1991;143: 1121-1129) was used as operational
      criteria for decision-making regarding antibiotic therapy. Patients with CPIS </=
      6 (implying low likelihood of pneumonia) were randomized to receive either
      standard therapy (choice and duration of antibiotics at the discretion of
      physicians) or ciprofloxacin monotherapy with reevaluation at 3 d; ciprofloxacin
      was discontinued if CPIS remained </= 6 at 3 d. Antibiotics were continued beyond
      3 d in 90% (38 of 42) of the patients in the standard as therapy compared with
      28% (11 of 39) in the experimental therapy group (p = 0.0001). In patients in
      whom CPIS remained </= 6 at the 3 d evaluation point, antibiotics were still
      continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of
      the patients in the experimental therapy group (p = 0.0001). Mortality and length
      of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost
      (p = 0.003) of antimicrobial therapy in the experimental as compared with the
      standard therapy arm. Antimicrobial resistance, or superinfections, or both,
      developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of
      37) of the patients in the standard therapy group (p = 0.017). Thus,
      overtreatment with antibiotics is widely prevalent, but unnecessary in most
      patients with pulmonary infiltrates in the ICU. The operational criteria used,
      regardless of the precise definition of pneumonia, accurately identified patients
      with pulmonary infiltrates for whom monotherapy with a short course of
      antibiotics was appropriate. Such an approach led to significantly lower
      antimicrobial therapy costs, antimicrobial resistance, and superinfections
      without adversely affecting the length of stay or mortality.

PMID- 10934079
TI  - Relation between phase of menstrual cycle and emergency department visits for
      acute asthma.
AB  - Hormonal fluctuations during the menstrual cycle are hypothesized to influence
      the course of asthma among women. A recent study found that almost 50% of
      emergency department (ED) visits occur during the perimenstrual phase. Our
      prospective cohort study in 64 EDs examined the relation between phase of
      menstrual cycle and visits for acute asthma. A total of 288 women with acute
      asthma were evaluated with a standardized patient interview and medical record
      review after excluding subjects who were pregnant, on hormonal therapy,
      postmenopausal, status post hysterectomy, had incomplete reproductive data, or
      whose ED visit fell more than 28 d after their last menstrual period. Only 13%
      reported reproductive factors as a personal asthma trigger. For all subjects, ED
      asthma visits were classified by menstrual phase: 33% were preovulatory (Days 5
      to 11), 26% were periovulatory (Days 12 to 18), 20% were postovulatory (Days 19
      to 25), and 21% were perimenstrual (Days 26 to 4), p = 0.008. There was no
      significant association between phase of menstrual cycle and asthma severity. Our
      data indicate that ED visits for acute asthma among women are more frequent
      during the preovulatory phase in contrast to other studies reporting more visits
      in the perimenstrual phase.

PMID- 10934080
TI  - Long-term follow-up of hexamethylene diisocyanate-, diphenylmethane diisocyanate
      , and toluene diisocyanate-induced asthma.
AB  - In 1976-1992 245 new cases of asthma induced by diisocyanates were diagnosed,
      caused by hexamethylene diisocyanate (HDI) in 39%, diphenylmethane diisocyanate
      (MDI) in 39%, and toluene diisocyanate (TDI) in 17% of the cases. Our aim was to
      study the clinical outcome of diisocyanate-induced asthma. A questionnaire was
      sent to the 235 patients alive in 1995, and validated by reexamining clinically
      91 of them. The study was carried out on average 10 () yr after the diagnosis. Of
      the patients 82% experienced symptoms of asthma, 34% used no medication, and 35%
      were on regular medication. The patients having displayed immunoglobulin E (IgE)
      antibodies to isocyanates used less medication (OR 0.273; CI 0.098, 0.758) and
      had fewer symptoms of asthma (OR 0.329; CI 0.124, 0.875) than the IgE-negative
      ones. They also had a significantly shorter duration of symptoms (p = 0.0025),
      latency period (p = 0.0249), and duration of exposure (p = 0.0008) than the IgE
      negative patients. This did not, however, entirely explain the more favourable
      outcome of the IgE-positive patients. Patients with HDI-induced asthma used less
      medication (OR 0.412; CI 0.229, 0.739) than patients with MDI- and TDI-induced
      asthma. The results confirm the generally rather poor medical outcome of
      diisocyanate-induced asthma; the persistence of symptoms and unspecific bronchial
      reactivity were pronounced in TDI-induced asthma. A more favourable outcome was
      associated with IgE mediation and HDI inducement.

PMID- 10934081
TI  - Effect of recombinant human platelet-activating factor-acetylhydrolase on
      allergen-induced asthmatic responses.
AB  - Platelet-activating factor (PAF) is a potent lipid mediator associated with key
      features of asthma such as airway constriction, eosinophil infiltration, edema,
      and mucus accumulation. Regulation of PAF occurs primarily through degradation to
      biologically inactive lyso-PAF by cellular and secreted PAF-acetylhydrolase (PAF
      AH). We evaluated the effect of human recombinant PAF-AH (rPAF-AH) on the dual
      phase asthmatic response in atopic subjects with mild asthma. Effects on induced
      sputum cell counts and differentials, eosinophilic cationic protein (ECP), and
      tryptase were evaluated. Enrolled subjects demonstrated a positive skin test and
      a dual asthmatic response to allergen inhalation challenge. Fourteen subjects
      received rPAF-AH (1 mg/kg) or placebo intravenously in a randomized, double
      blind, placebo-controlled, two-period crossover study. Treatment with rPAF-AH did
      not significantly reduce either the early- or late-asthmatic response. Sputum
      eosinophil cell counts were not affected by treatment, but there was a trend
      toward a reduction in sputum neutrophils. No significant change in sputum ECP and
      tryptase was observed between rPAF-AH and placebo. Thus, at the dose studied, the
      unique anti-PAF agent rPAF-AH demonstrated no significant effect on the allergen
      induced dual-phase asthmatic response.

PMID- 10934082
TI  - Prostaglandin E(2) enhances chemical and mechanical sensitivities of pulmonary C
      fibers in the rat.
AB  - It has been recently reported that pulmonary reflex responses to injection or
      inhalation challenge of capsaicin are enhanced by exogenous Prostaglandin E(2)
      (PGE(2)). The present study was carried out to determine whether PGE(2) enhances
      the stimulatory effects of chemical stimulants and lung inflation on vagal
      pulmonary C fibers, and if so, whether the excitabilities of other types of lung
      afferents are also augmented by PGE(2). In anesthetized, open-chest rats,
      administration of PGE(2) (1.5 microgram/kg/min for 2 min) did not significantly
      change the baseline activity of vagal pulmonary C fibers, but it markedly
      enhanced the stimulatory effects of both low (0.25 microgram/kg) and high doses
      (0.5 microgram/kg) of capsaicin on these fibers. Similarly, potentiating effects
      of PGE(2) were found on the pulmonary C-fiber responses to injections of lactic
      acid and adenosine, although considerable variability existed in the degrees of
      potentiation between the different stimulants. Furthermore, PGE(2) infusion also
      significantly enhanced the C-fiber response to constant-pressure lung inflation
      (tracheal pressure [Pt] = 30 cm H(2)O). In contrast, PGE(2) did not alter the
      responses of either slowly adapting pulmonary receptors or rapidly adapting
      pulmonary receptors to lung inflation. In summary, these results show that the
      sensitivity of pulmonary C-fiber afferents to both mechanical and chemical
      stimuli is enhanced by PGE(2), suggesting that endogenous release of this
      autocoid may play a part in the airway irritation and dyspneic sensation
      associated with airway inflammation.

PMID- 10934083
TI  - Muscarinic control of histamine release from airways. Inhibitory M1-receptors in
      human bronchi but absence in rat trachea.
AB  - Isolated human bronchi and rat tracheae were incubated in organ baths to measure
      histamine release. The calcium ionophore A23187, 3 micromol/L in rat trachea and
      10 micromol/L in human bronchi, stimulated histamine release by 145 +/- 50% (n =
      6) and 270 +/- 48% (n = 7) above the prestimulation level, respectively.
      Acetylcholine (100 pmol/L; human bronchi) or oxotremorine (1, 100, 10,000 nmol/L;
      rat trachea) did not affect the spontaneous histamine release. In rat tracheae
      neither acetylcholine nor oxotremorine inhibited A23187-evoked histamine release,
      whereas 100 pmol/L acetylcholine significantly suppressed the evoked histamine
      release in human bronchi by 86%. For receptor characterization the following
      subtype-specific muscarinic receptor antagonists were applied: pirenzepine (M1
      subtype), para-fluorohexahydrosiladifendiol (pFHHSiD; similar affinities at human
      cloned M1-, M3-, and M4-receptors), AF-DX 116 (M2 subtype), and clozapine
      (antagonist at cloned M1-, M2-, M3-receptors; agonist at cloned M4-receptors).
      Pirenzepine, pFHHSiD, AF-DX 116, and clozapine (100 nmol/L each) antagonized the
      inhibitory effect of 100 pmol/L acetylcholine by 83 +/- 20% (n = 6), 83 +/- 9% (n
      = 8), 50 +/- 14% (n = 6), and 35 +/- 7% (6). In conclusion, a species difference
      exists in the cholinergic control of histamine release between human and rat
      airways. In human airways muscarinic receptors most likely of the M1 subtype are
      involved in the inhibitory control of mast cell function, whereas such an
      inhibitory pathway does not exist in the rat trachea.

PMID- 10934084
TI  - FE(NO): relationship to exhalation rates and online versus bag collection in
      healthy adolescents.
AB  - Measurement of exhaled nitric oxide (FE(NO)) is a noninvasive and practical
      method for assessing airway inflammation. We conducted this investigation to
      determine the most appropriate flow rate for FE(NO) measurement and to obtain
      normal values for FE(NO). We determined which expiratory flow was easy to
      sustain, generated reproducible values, and provided good correlation between
      offline and online measurements. Thirty-two healthy subjects (15- 18 yr old)
      underwent spirometry and FE(NO) measurements, using a chemiluminescent NO
      analyzer at expiratory flow rates of 46, 31, 23, 15, 10, 7, 5, and 4 ml/s. The
      major findings were as follows: (1) FE(NO) increased as flow rates decreased,
      with strong correlation between FE(NO) values and flow rates at the four highest
      flows (0. 85- 0.93, p < 0.001); (2) there were no significant differences and
      good agreement between offline bag and online FE(NO) values for the four highest
      flows (p < 0.09-0.83); (3) online FE(NO) values increased with age 15-17 yr at
      all flow rates, but decreased at age 18 yr; and (4) using multiple regression,
      significant predictors of FE(NO) were flow, body surface area, age, and FEF(25
      75). On the basis of these results, we provide FE(NO) values for healthy
      adolescents and propose that the ideal flow rate for children is between 30 and
      50 ml/s.

PMID- 10934085
TI  - Assessment of neural inspiratory time in ventilator-supported patients.
AB  - Neural inspiratory time (TI) is a measurement of fundamental importance in
      studies of patient-ventilator interaction. The measurement is usually based on
      recordings of flow, esophageal pressure (Pes), and transdiaphragmatic pressure
      (Pdi), but the concordance of such estimates of neural TI with a more direct
      measurement of neural activity has not been systematically evaluated. To address
      this issue, we studied nine ventilator-supported patients in whom we employed
      esophageal electrode recordings of the diaphragmatic electromyogram (EMG) as the
      reference measurement of neural TI. Comparison of the indirect estimates of
      neural TI duration, based on flow, Pes, and Pdi against the reference
      measurement, revealed a mean difference (bias) ranging from -54 to 612 ms during
      spontaneous breathing and from -52 to 714 ms during mechanical ventilation; the
      respective precisions (standard deviations of the differences) ranged from 79 to
      175 ms and from 74 to 221 ms. Because an indirect estimate of neural TI duration
      could be identical to that of the reference measurement and yet be displaced in
      time, this lag or lead was quantified as the phase angle of neural TI onset. Flow
      based estimates of the onset of neural TI displayed a systematic lag, which may
      be explained at least in part by concurrent intrinsic positive end-expiratory
      pressure. In conclusion, the indirect estimates of the onset and duration of
      neural TI in ventilator-dependent patients displayed poor agreement with the
      diaphragmatic EMG measurement of neural TI.

PMID- 10934086
TI  - Occupational exposure risks in individuals with PI*Z alpha(1)-antitrypsin
      deficiency.
AB  - We obtained questionnaire and spirometry data from 128 alpha(1)-antitrypsin
      (alpha(1)AT)-deficient individuals with phenotype PI*Z to examine the
      relationship between chronic respiratory symptoms, airflow limitation, treatment
      requirements, and semiquantitative estimates of occupational exposure to dust,
      fumes, smoke, and gas. After adjusting for age, smoking, and prior lower
      respiratory tract infections, increased prevalence of chronic cough (OR = 4.69,
      95% CI = 1.57-13.74, p = 0.006) and having left a job due to breathlessness (OR =
      2.72, 95% CI = 1.07-6.92, p = 0.036) were seen in individuals reporting high
      mineral dust exposure compared with those with no exposure. Subjects reporting
      high mineral dust exposure also had significantly lower FEV(1) (31% predicted for
      high exposure versus 36% for low and 40% for unexposed, p = 0.032). The excess
      risk of chronic cough seen with occupational fumes or smoke exposure disappeared
      after adjusting for mineral dust exposure, but the association with lower
      FEV(1)/FVC ratio persisted (p = 0.022). Personal tobacco use was a significant
      risk factor for most outcome measures, but no interaction with occupational
      exposure was seen. These results suggest that occupational inhalational exposures
      are independently associated with respiratory symptoms and airflow limitation in
      severely alpha(1)AT-deficient individuals.

PMID- 10934087
TI  - Influence of chemoreceptor stimuli on genioglossal response to negative pressure
      in humans.
AB  - Genioglossal muscle (GG) activity is modulated by both chemoreceptive and
      mechanoreceptive reflexes that help stabilize airway patency. We assessed the
      effects of blood gas changes, within the range encountered during mild
      obstructive apnea-arousal cycles, on GG activity and the GG reflex to upper
      airway negative pressure. Eighteen healthy adults were studied while awake under
      5 conditions: (1) baseline (PET(CO(2)) = 40 mm Hg, Sa(O(2)) = 99%); (2)
      hypercapnia (PET(CO(2)) = 45 mm Hg); (3) hypocapnia (PET(CO(2)) = 35 mm Hg,
      induced via hyperventilation with an iron lung ventilator); (4) hypoxia (Sa(O(2))
      = 87%); and (5) hypercapnia plus hypoxia (PET(CO(2)) = 45 mm Hg, Sa(O(2)) = 87%).
      Measurements included airflow, choanal and epiglottic pressures (Pchoa and Pepi),
      upper airway resistance, phasic and tonic GG EMG, and the GG reflex to negative
      pressure (Pchoa = -12.5 cm H(2)O). Ventilation increased from a baseline of 10.7
      up to 22.7 L. min(-1) under conditions of altered blood gases. Peak inspiratory
      phasic GG EMG increased from 6. 5 to 11.1% of maximal contraction but there were
      no significant changes in either tonic GG EMG (range, 4.3 to 5.8% of maximum) or
      magnitude of the GG reflex (range, 4.1 to 5.5% of maximum). Among conditions
      there was a high correlation between upper airway pressures and peak phasic GG
      EMG (Pchoa, r = 0.97, p < 0.01; Pepi, r = 0.87; p = 0.06). We conclude that in
      this range of blood gases: (1) the GG reflex to negative pressure is unchanged;
      (2) slow airway pressure changes throughout inspiration, generated either
      actively or passively, influence GG EMG activity; and (3) mechanoreceptive
      control of GG EMG can fully explain all changes in GG activity, suggesting that
      chemoreceptive inputs to GG are minimal, or are not simply summated with
      mechanoreceptor inputs.

PMID- 10934088
TI  - Enhanced release of superoxide from polymorphonuclear neutrophils in obstructive
      sleep apnea. Impact of continuous positive airway pressure therapy.
AB  - Obstructive sleep apnea (OSA) is associated with increased cardiovascular
      morbidity and mortality. Free oxygen radicals have been implicated in the
      pathogenesis of cardiovascular disorders. Therefore, we aimed to test the
      hypothesis that increased oxidative stress constitutes one underlying mechanism
      for the connection between OSA and cardiovascular disease. In 18 patients with
      OSA the release of superoxide from polymorphonuclear neutrophils was determined
      after stimulation with the bacterial tripeptide
      formylmethionylleucylphenylalanine (fMLP) and the calcium ionophore A23.
      Superoxide production was measured as superoxide dismutase-inhibitable reduction
      of cytochrome c. Blood samples were obtained before and after two nights of CPAP
      therapy and after 4.8 +/- 0.6 mo of follow-up. Ten healthy young volunteers and
      10 lung cancer patients without OSA but a similar spectrum of comorbidity served
      as controls. Before CPAP, neutrophil superoxide generation was markedly enhanced
      in OSA when compared with both control groups. Effective CPAP therapy led to a
      rapid and long-lasting decrease of superoxide release in OSA. In conclusion, OSA
      is linked with a "priming" of neutrophils for enhanced respiratory burst. The
      increased superoxide generation, which might have major impact on the development
      of cardiovascular disorders, is virtually fully reversed by effective CPAP
      therapy.

PMID- 10934089
TI  - Cryptogenic organizing pneumonia. Characteristics of relapses in a series of 48
      patients. The Groupe d'Etudes et de Recherche sur les Maladles "Orphelines"
      Pulmonaires (GERM"O"P).
AB  - Cryptogenic organizing pneumonia (COP) is a clinicopathologic syndrome
      characterized by rapid resolution with corticosteroids, but frequent relapses
      when treatment is tapered or stopped. We retrospectively studied relapses in 48
      cases of biopsy-proven COP. One or more relapses (mean 2.4 +/- 2.2) occurred in
      58%. At first relapse, 68% of patients were still under treatment for the initial
      episode. Compared with the no-relapse group, nine patients with multiple (>/= 3)
      relapses had longer delays between first symptoms and treatment onset (22 +/- 17
      versus 11 +/- 8 wk, p = 0.02), and elevated gamma-glutamyltransferase (124 +/- 98
      versus 29 +/- 13 IU/L, p = 0.001) and alkaline phosphatase (190 +/- 124 versus
      110 +/- 68 IU/L, p = 0.04) levels. Relapses did not adversely affect outcome.
      Corticosteroid treatment side effects occurred in 25% of patients. Standardized
      treatment in 14 patients allowed a reduction of prednisone cumulated doses (p <
      0.05) without affecting outcome or relapse rate. We conclude that: (1) delayed
      treatment increases the risk of relapses; (2) mild cholestasis identifies a
      subgroup of patients with multiple relapses; (3) relapses do not affect outcome,
      and prolonged therapy to suppress relapses appears unnecessary; (4) a
      standardized treatment allows a reduction in steroid doses.

PMID- 10934090
TI  - Zafirlukast improves asthma control in patients receiving high-dose inhaled
      corticosteroids.
AB  - Not all asthma can be adequately controlled, despite the use of high-dose inhaled
      corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in
      the pathogenesis of asthma, we hypothesized that the leukotriene receptor
      antagonist zafirlukast, in combination with high-doses of inhaled
      corticosteroids, might be efficacious in severe asthma. In a double-blind,
      parallel group study, 368 chronic adult asthmatic patients treated with inhaled
      corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of
      asthma symptoms during the run in period of the study, were randomly assigned to
      receive additional treatment with a high dose of zafirlukast (80 mg twice daily)
      (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast
      produced a significant improvement over baseline in the primary study endpoint of
      mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p <
      0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom
      score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast
      significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]:
      0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients
      requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2
      to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids,
      zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk
      of an asthma exacerbation, suggesting that the contribution of leukotrienes to
      asthma symptoms and exacerbations is not adequately controlled by high-dose
      inhaled corticosteroids.

PMID- 10934091
TI  - CC chemokines and interleukin-5 in bronchial lavage fluid from patients with
      status asthmaticus. Potential implication in eosinophil recruitment.
AB  - In status asthmaticus (SA), severe bronchial inflammation is associated with
      acute respiratory failure. Neutrophils are the prominent cells found in bronchi
      from SA patients, but eosinophils are also recruited within the first 48 h after
      the beginning of mechanical ventilation (MV). Interleukin (IL)-5 and CC
      chemokines have been directly implicated in the pathophysiology of allergic
      asthma. However, their involvement in SA had not been determined. The aim of this
      study was to evaluate the production of CC chemokines and of IL-5 in airways from
      ventilated patients with SA as compared with mild asthma (A), and to assess the
      role of these mediators in eosinophil recruitment. We measured levels of the
      chemokines monocyte chemotactic proteins (MCPs)-1 and -3; regulated on
      activation, normal T-cell expressed and secreted (RANTES); macrophage
      inflammatory peptide (MIP)-1alpha; and eotaxin; and of the cytokine IL-5 in
      bronchial lavage fluid (BLF) from 10 SA patients, four patients without
      respiratory disease but undergoing ventilation (V) who were receiving MV, 11
      patients with A, and eight healthy volunteers (C). We further evaluated in vitro
      eosinophil chemotactic activity of BLF from the various groups. Levels of MCP-1,
      MIP-1alpha, RANTES, and IL-5 were significantly higher in the SA than in the V,
      A, and C groups. MCP-3 and eotaxin values were not significantly different in the
      SA and other groups; however, their levels, as well as those of MIP-1alpha,
      RANTES, and IL-5 correlated with eosinophil influx. Eosinophil chemotactic
      activity in BLF was increased in asthmatic subjects (A and SA groups) as compared
      with the other groups, and in SA patients as compared with A patients. Addition
      of neutralizing anti-IL-5, anti-MCP-3, anti-eotaxin, and anti-RANTES antibodies
      significantly inhibited the eosinophil chemotactic activity as compared with that
      of native BLF. This study shows that the levels of various CC chemokines and IL-5
      are increased in airways of SA patients, and are potentially involved in
      eosinophil recruitment.

PMID- 10934092
TI  - Comparable efficacy of administration with face mask or mouthpiece of nebulized
      budesonide inhalation suspension for infants and young children with persistent
      asthma.
AB  - A randomized, double-blind, placebo-controlled, parallel-group study including
      481 children at 37 centers in the United States demonstrated the efficacy and
      safety of budesonide inhalation suspension in doses of 0.25 mg once daily, 0.25
      mg twice daily, 0.5 mg twice daily, and 1.0 mg daily in infants and young
      children with persistent asthma. The retrospective analysis presented here
      compares the efficacy of treatment with the suspension administered through a
      face mask or mouthpiece. All patients receiving budesonide inhalation suspension
      via face mask or mouthpiece showed clinical improvements in nighttime and daytime
      asthma symptoms as compared with administration of a placebo. The improvements
      were of similar magnitude as those observed in an analysis of all patients
      treated. Improvements in nighttime asthma symptoms were statistically significant
      with budesonide at 0.25 mg daily (p = 0.040), 0.25 mg twice daily (p = 0.008),
      and 0.5 mg twice daily (p = 0.046) delivered by face mask. In patients using
      mouthpieces, nighttime asthma symptoms improved significantly in the 0.25-mg
      twice-daily (p = 0.005) and 1.0-mg daily (p = 0.035) groups. Patients receiving
      budesonide at 0.5 mg twice daily via a face mask improved significantly in
      daytime asthma symptoms (p = 0.009). The use of breakthrough medication was
      reduced in patients receiving budesonide via face masks or mouthpieces relative
      to placebo, and treatment was well tolerated in all study groups. This
      retrospective analysis suggests that nebulized budesonide inhalation suspension
      can be administered effectively by either face mask or mouthpiece to young
      children with persistent asthma.

PMID- 10934093
TI  - beta(2)-adrenergic receptor Arg16/Arg16 genotype is associated with reduced lung
      function, but not with asthma, in the Hutterites.
AB  - In a genome-wide screen for asthma loci in the Hutterites, a marker locus on
      chromosome 5q23-31 showed evidence of linkage to asthma (C. Ober and colleagues,
      Hum. Molec. Genet. 1998;7:1393). To determine whether the beta(2)-adrenergic
      receptor (beta(2)AR) gene is the 5q-linked asthma locus in the Hutterites, we
      genotyped this sample for polymorphisms in the beta(2)AR gene. Neither the
      Arg16Gly nor Gln27Glu polymorphisms showed evidence of linkage to qualitative
      measures of asthma and bronchial hyperresponsiveness (BHR) (p > 0.10) or to
      quantitative measures of serum IgE and airway reactivity (p > 0.10). In contrast,
      FEV(1) percentage of predicted and FVC percentage of predicted were significantly
      lower among individuals homozygous for the Arg16 allele (FEV(1) %: 98.3 +/- 13.2%
      versus 103. 8 +/- 14.9%, p = 0.003; FVC %: 104.2 +/- 12.3% versus 108.3 +/- 13.
      2%, p = 0.02 by t test). These findings held true for adolescents and adults, but
      not for children </= 12 yr of age. This study demonstrates that the observed
      linkage to asthma in the 5q23-31 region is unrelated to variation in the
      beta(2)AR gene. However, it is the first study to suggest that the beta(2)AR
      Arg16Gly polymorphism influences either lung growth or the rate of decline of
      lung function with age.

PMID- 10934094
TI  - A small-molecule, tight-binding inhibitor of the integrin alpha(4)beta(1) blocks
      antigen-induced airway responses and inflammation in experimental asthma in
      sheep.
AB  - The leukocyte integrin very late antigen-4 (alpha(4)beta(1), CD49d/CD29) is an
      adhesion receptor that plays an important role in allergic inflammation and
      contributes to antigen-induced late responses (LAR) and airway
      hyperresponsiveness (AHR). In this study, we show that single doses of a new
      small-molecule, tight-binding inhibitor of alpha(4), BIO-1211, whether given by
      aerosol or intravenously, either before or 1.5 h after antigen challenge blocks
      allergen- induced LAR and post-antigen-induced AHR in allergic sheep. Multiple
      treatments with doses of BIO-1211 that were ineffective when given singly, were
      protective. BIO-1211 also provided dose-dependent inhibition of the early airway
      response (EAR) to antigen. In conjunction with the functional protection against
      the antigen-induced LAR and AHR, sheep treated with BIO-1211 before challenge
      showed significantly reduced: (1) numbers of eosinophils in bronchoalveolar
      lavage (BAL), (2) BAL levels of the inflammatory marker tissue kallikrein, and
      (3) numbers of inflammatory cells (lymphocytes, eosinophils, metachromatic
      staining cells, and neutrophils) in bronchial biopsies obtained after challenge
      when compared with corresponding biopsies after vehicle treatment. More
      importantly, we show for the first time that an inhibitor of alpha(4) was able to
      reverse post-antigen-induced AHR, thereby decreasing the time of recovery from
      the normal period of > 9 d to 3 d. Our results show that effective inhibition of
      antigen-induced airway responses can be achieved with single doses of a potent
      small-molecule inhibitor of alpha(4) and that such agents may be used
      therapeutically, as well as prophylactically, to alleviate allergen- induced
      inflammatory events. These data provide further support and extend the evidence
      for the role of alpha(4) integrins in the pathophysiologic events that follow
      airway antigen challenge.

PMID- 10934095
TI  - Permanent declines in pulmonary function following pneumonia in human
      immunodeficiency virus-infected persons. The Pulmonary Complications of HIV
      Infection Study Group.
AB  - Human immunodeficiency virus (HIV)-associated respiratory infections, most
      notably Pneumocystis carinii pneumonia (PCP), but also bacterial pneumonia (BP),
      result in reductions in lung function that have been studied mainly during the
      course of acute infection. Whether HIV-associated pneumonias also cause permanent
      changes in pulmonary function is unknown. In this study we investigated the long
      term effects of PCP and BP on pulmonary function in a cohort of HIV-infected
      persons. One thousand, one hundred forty-nine HIV-infected persons were followed
      in a prospective, observational cohort study at six centers in the United States.
      Study participants had pulmonary function testing performed at regular preset
      intervals. PCP and BP diagnoses were verified with defined criteria. Longitudinal
      multivariate analysis was used to model pulmonary function in terms of
      demographic data and occurrence of PCP or BP. We found that PCP or BP was
      associated with permanent decreases in FEV(1), FVC, FEV(1)/FVC, and the diffusing
      capacity of carbon monoxide. Neither infection resulted in statistically
      significant changes in TLC. We conclude that PCP and BP result in expiratory
      airflow reductions that persist after the acute infection resolves. The clinical
      implications of these changes are unknown, but they may contribute to prolonged
      respiratory complaints in HIV-infected patients who have had pneumonia.

PMID- 10934096
TI  - Separation of alveolar surfactant into subtypes. A comparison of methods.
AB  - Alveolar surfactant is known to exist in several morphologic forms or subtypes
      which have been separated from bronchoalveolar lavage fluid (BAL) by two types of
      methods-differential centrifugation (DC) and equilibrium buoyant density gradient
      centrifugation (EBDC). DC separates BAL into large aggregates (LA) and small
      aggregates (SA); EBDC separates BAL into three peaks called ultraheavy (UH),
      heavy (H), and light (L). We compared these two separation methods by subjecting
      replicates of the same pools of BALF from groups of mice to DC and EBDC in
      parallel assays. We found that each method was highly internally consistent, but
      that the amount of phospholipid in the LA fraction of DC was consistently and
      substantially less (by 33 to 43%) than that found in the UH + H fractions of
      EBDC. This appeared to be due to failure of DC to sediment all of the
      phospholipid that banded as UH or H in EBDC despite adjustments in the time and g
      force of DC. In experiments where differentially labeled purified H and L
      subtypes were subjected to DC over a wide range of g-force and time conditions,
      cross-contamination of the DC pellet and supernatant with heterologous subtypes
      was always present (4 to 33% cross-contamination). Addition of extraneous serum
      proteins to the BAL, as a model of lung damage, resulted in further
      inconsistencies in DC but not EBDC. Investigators may wish to bear these
      considerations in mind when planning or interpreting the results of experiments
      bearing on surfactant subtype analysis.

PMID- 10934097
TI  - Polymer-surfactant treatment of meconium-induced acute lung injury.
AB  - Substances (for example, serum proteins or meconium) that interfere with the
      activity of pulmonary surfactant in vitro may also be important in the
      pathogenesis or progression of acute lung injury. Addition of polymers such as
      dextran or polyethylene glycol (PEG) to surfactants prevents and reverses
      surfactant inactivation. The purpose of this study was to find out whether
      surfactant/polymer mixtures are more effective for treating one form of acute
      lung injury than is surfactant alone. Acute lung injury in adult rats was created
      by tracheal instillation of human meconium. Injured animals, which were
      anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with
      surfactant mixtures, remained hypoxic and required high ventilator pressures to
      maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured
      animals maintained normal values for oxygen and compliance of the respiratory
      system. The greatest improvement in both oxygenation (178%) and compliance (42%)
      occurred in animals with lung injury that were treated with Survanta and PEG
      (versus untreated control animals; p < 0.01), whereas little improvement was
      found after treatment with Survanta alone. Similar results were found when
      postmortem pulmonary pressure-volume curves and histology were examined. We
      conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics,
      and histologic appearance of the lungs in a rat model of acute lung injury caused
      by meconium.

PMID- 10934098
TI  - Neutrophil-dependent and neutrophil-independent alterations in the nasal
      epithelium of ozone-exposed rats.
AB  - Ozone induces epithelial hyperplasia and mucous cell metaplasia (MCM) in nasal
      transitional epithelium (NTE) of rats. A transient neutrophil influx accompanies
      upregulation of mucin messenger RNA (mRNA) before the onset of MCM. The present
      study was designed to examine the role of neutrophils in ozone-induced epithelial
      changes in the NTE of rats. Fourteen hours before inhalation exposure, male
      F344/N rats were injected intraperitoneally with antirat neutrophil antiserum to
      deplete circulating neutrophils, or were injected with normal (control) serum.
      Rats were then exposed to 0 ppm (filtered air) or 0.5 ppm ozone (8 h/d) for 1 or
      3 d. Maxilloturbinates lined with NTE were analyzed to determine the epithelial
      labeling index; numeric densities of neutrophils, total epithelial cells, and
      mucous secretory cells; amount of stored intraepithelial mucosubstances; and
      steady-state ratMUC-5AC (mucin) mRNA levels. At 2 h after 3 d of exposure, rats
      treated with antiserum had 90% fewer circulating neutrophils than did rats
      treated with control serum. Antiserum-treated, ozone-exposed rats had 87% fewer
      infiltrating neutrophils than did control serum-treated, ozone-exposed rats. At 4
      d after 3 d of exposure, antiserum-treated, ozone-exposed rats had 66% less
      stored intraepithelial mucosubstances and 58% fewer mucous cells in their NTE
      than did control serum-treated, ozone-exposed rats. Antiserum treatment had no
      effects on ozone-induced epithelial cell proliferation or mucin mRNA
      upregulation. The results of this study indicated that ozone-induced MCM was
      neutrophil-dependent, whereas ozone-induced epithelial cell proliferation and
      mucin gene upregulation were neutrophil-independent.

PMID- 10934099
TI  - Prostaglandin E(2) decreases allergen-stimulated release of prostaglandin D(2) in
      airways of subjects with asthma.
AB  - Prostaglandin E(2) (PGE(2)) inhibits the early and late bronchoconstrictor
      response to inhaled allergen. The mechanisms of action, however, are not
      understood. We investigated the effect of inhaled PGE(2) on the release of
      prostaglandin D(2) (PGD(2)), preformed mast cell mediators, and other products of
      arachidonic acid metabolism. We compared inhaled PGE(2) (100 microgram) to
      placebo in a randomized double-blind crossover study. Ten atopic asthmatics
      underwent bronchoscopy immediately after inhalation of PGE(2) or placebo.
      Bronchoalveolar lavage (BAL) was performed at baseline, and in a separate segment
      4 min after allergen instillation. Nebulized PGE(2) was well tolerated. PGE(2)
      concentrations in baseline lavage fluid were significantly greater after PGE(2)
      inhalation than after placebo. PGD(2) concentrations after allergen challenge
      were significantly reduced in those subjects receiving nebulized PGE(2) compared
      with control subjects. We conclude that PGE(2) can be safely delivered by
      inhalation. Nebulized PGE(2) administered before to segmental allergen challenge
      reduced PGD(2) in BAL fluid (BALF). PGE(2) also decreased the production of other
      mediators of the arachidonic acid pathway, although not significantly. The
      reduction of PGD(2) may be part of the mechanism by which PGE(2) blocks the early
      asthmatic response.

PMID- 10934100
TI  - Obstructive sleep apnea syndrome. fifty-one consecutive patients treated by
      maxillofacial surgery.
AB  - The place of surgical treatment in obstructive sleep apnea syndrome (OSAS)
      remains unclear. Uvulopalatopharyngoplasty (UPPP) has a response rate of 41%
      overall and only 5% when retrolingual narrowing is present. Thus, in cases with
      suspected hypopharyngeal collapse maxillofacial surgery has been proposed with
      improved results. The Stanford group has designed a step-by-step surgical
      procedure tailored to the specific anatomical abnormalities encountered in each
      patient. The goal is to avoid a full maxillomandibular advancement osteotomy
      (MMO), at least in a subgroup of patients, beginning with a limited mandibular
      osteotomy (with or without hyoid myotomy and hyothyroidopexy and with or without
      UPPP) (phase 1 surgery). In this procedure MMO is performed as the second or
      third step (phase 2 surgery). The present study reports on our prospective
      experience with 51 consecutive patients (64 surgical procedures) treated by the
      step-by-step maxillofacial surgery previously described by the Stanford team.
      Only 2 of the 53 patients initially treated were lost for follow-up. Surgery was
      considered a success if the postoperative apnea and hypopnea index (AHI) was less
      than 15/h with at least a 50% reduction. Forty-four patients had phase 1 surgery.
      The success rate was 22.7% (10 of 44). The mean AHI was unchanged with a trend
      for reduction in the apnea index. Twenty patients had maxillomandibular
      advancement surgery (phase 2) (13 failures of phase 1, 7 patients primarily
      because of facioskeletal deformities). The AHI decreased from 59 +/- 29/h to 11
      +/- 9/h after phase 2. Of the patients 75% (15 of 20) were considered to have had
      a successful outcome. In conclusion, phase 1 does not seem effective in most
      patients with OSAS. The results of phase 2 surgery are successful in young
      patients with severe OSAS even if the surgical technique is more aggressive.

PMID- 10934101
TI  - Partial liquid ventilation ventilates better than gas ventilation.
AB  - Partial liquid ventilation (PLV) improves oxygenation in several models of lung
      injury. However, PLV has only been compared with conventional gas ventilation
      (GV) with low PEEP. Both PLV and GV can markedly improve oxygenation when PEEP is
      set above the lower corner pressure (Plc) on the inspiratory pressure-volume (P
      V) curve of the total respiratory system. We questioned if the use of PEEP set
      above the Plc during PLV and GV would result in similar gas exchange. Lung injury
      was induced in 12 sheep by saline lavage before randomization to PLV (n = 6) or
      GV (n = 6). Animals in the PLV group were filled with perflubron (22 ml/kg) until
      a meniscus at the teeth was observed. Both groups were then ventilated with
      pressure control (FI(O(2)), 1.0; rate, 20/min; I:E, 1:1) and PEEP (1 cm H(2)O
      above the Plc on the inspiratory P-V curve). Peak inspiratory pressure (PIP) was
      limited to 35 cm H(2)O. Animals were ventilated for 5 h and then killed for
      histologic examinations. All 12 animals survived the 5-h ventilation period.
      After increasing PEEP above Plc, Pa(O(2)) increased significantly (p < 0.01) in
      both the GV and the PLV groups, but it did not differ significantly between
      groups (p = 0.86) at any time during the experiment. Pa(CO(2)) and VD/VT in GV
      increased markedly throughout the experiment after increasing PEEP (p < 0.001),
      but there was no significant change in Pa(CO(2)) in PLV (p = 0.13). Mean arterial
      blood pressure, mean pulmonary artery pressure, pulmonary artery occlusion
      pressure, and central venous pressure, increased and SVR decreased in GV (p <
      0.05). The extent and the severity of lung injury in the dependent regions was
      greater in the GV group (p < 0.05). Both PLV and GV improved oxygenation, but PLV
      resulted in better ventilation than GV while preserving lung structure when PEEP
      was set 1 cm H(2)O above the Plc and PIP limited to 35 cm H(2)O.

PMID- 10934102
TI  - Serological diagnosis of idiopathic pulmonary alveolar proteinosis.
AB  - Previously, we reported the specific occurrence of neutralizing autoantibodies
      against granulocyte-macrophage colony-stimulating factor (GM-CSF) in the
      bronchoalveolar lavage fluid from 11 Japanese patients with idiopathic pulmonary
      alveolar proteinosis (I-PAP). The autoantibody was also detected in sera from all
      5 I-PAP patients examined. To determine that the existence of the autoantibody is
      not limited to the Japanese patients, we examined sera from 24 I-PAP patients in
      five countries and showed that the autoantibody was consistently and specifically
      present in such patients. Thus, detection of the autoantibody in sera can be used
      for diagnosis of I-PAP. To establish a simple and convenient method for diagnosis
      of I-PAP, we developed a novel latex agglutination test using latex beads coupled
      with recombinant human GM-CSF. GM-CSF binding proteins isolated from the sera
      using the latex beads were identified as the autoantibodies of IgG(1) and IgG(2).
      The titer of the autoantibody determined by this test correlated with that
      determined by ELISA. Agglutination was positive in 300-fold diluted sera from all
      24 I-PAP patients, but negative in sera from four secondary PAP patients, two
      congenital PAP patients, 40 patients with other lung diseases, and 38 of 40
      normal subjects. These results establish that the latex agglutination test is a
      reliable method for serological diagnosis of I-PAP with high sensitivity (100%)
      and specificity (98%).

PMID- 10934103
TI  - The effect of age and duration of disease on airway structure in fatal asthma.
AB  - We hypothesized that if airway remodeling is related to duration of asthma, that
      when matched for severity, the airways of older adults should show greater
      alterations than the airways of younger adults. Using standard morphometric
      techniques, we compared airways with basement membrane perimeters (Pbm) between 2
      and 10 mm from young individuals who died of asthma (n = 14, range 17-23 yr), and
      older individuals with fatal asthma (n = 13, range 40-49 yr). Comparisons were
      also made with normal airways from age-matched adults. Wall area was increased in
      old individuals with fatal asthma compared with young individuals with fatal
      asthma, primarily due to greater adventitial area, whereas wall area in young
      individuals with fatal asthma was not different from control subjects. Within
      muscle bundles the connective tissue matrix was increased around individual cells
      in individuals with asthma, unrelated to age. After adjustment for this change,
      smooth muscle area in both asthma groups was still greater than in age-matched
      control subjects, in old individuals with fatal asthma 4-fold greater (p = 0.04),
      and in young individuals with fatal asthma 2-fold greater (p = 0.03). Airway
      narrowing was increased in old versus young individuals with fatal asthma, with
      both groups more narrowed than control subjects. Intralumenal obstruction and
      subepithelial collagen in the two asthma groups were significantly greater than
      in control subjects, but there was no age effect. These data provide support for
      the hypothesis that there is an increase in airway wall area, including smooth
      muscle, and airway narrowing with increasing duration of severe asthma or with
      older age. The observation that total wall thickness was not greater in young
      individuals with young fatal asthma than in control subjects suggests that
      factors other than airway wall geometry contribute to the pathogenesis of fatal
      attacks in this age group.

PMID- 10934104
TI  - Left atrial and ventricular filling in chronic obstructive pulmonary disease. An
      echocardiographic and Doppler study.
AB  - Abnormal left ventricular (LV) diastolic function has frequently been reported in
      patients with chronic obstructive pulmonary disease (COPD). In the present work,
      diastolic function was studied by a combined analysis of pulmonary venous and
      mitral blood flow velocities in 34 patients with COPD clinically stable and
      without history of heart disease, and 20 control subjects. We confirmed the
      increased contribution of the atrial contraction to the LV filling in COPD
      patients in comparison with control subjects; furthermore, a decreased left
      atrial (LA) filling during the ventricular systole was observed. Changes in LV
      filling were not the consequence of a systolic dysfunction, because LV systolic
      function was normal. Doppler indices indicated that LA pressure was below 15 cm
      H(2)O in all the patients with COPD and control subjects. Several factors can be
      put forward to explain these changes; the first one is tachycardia. In addition
      to hypoxemia and medications, echocardiography suggested that a decreased LV
      preload participated in increased heart rate. Analysis of Doppler transmitral and
      pulmonary venous flows demonstrated the role of the ventricular interdependence
      because a correlation existed between LA and LV filling pattern and right
      ventricle pressure and diameter.

PMID- 10934105
TI  - Cyclooxygenase inhibition increases interleukin 5 and interleukin 13 production
      and airway hyperresponsiveness in allergic mice.
AB  - The immunomodulatory role of arachidonic acid metabolites in allergic
      sensitization is undefined. Prostaglandin E(2) (PGE(2)), a product of arachidonic
      acid metabolism through the cyclooxygenase pathway, has been reported to favor
      Type 2-like cytokine secretion profiles in murine and human CD4(+) T cells by
      inhibiting the production of Type 1-associated cytokines. On the basis of these
      in vitro data, we hypothesized that indomethacin, a nonselective cyclooxygenase
      inhibitor, would diminish allergen-induced production of Type 2 cytokines in
      mice, and protect against airway hyperresponsiveness (AHR) to methacholine. We
      found that ovalbumin-sensitized mice that were treated with indomethacin (OVA
      indomethacin mice) had significantly greater AHR (p < 0.05) and higher levels of
      IL-5 (176 +/- 52 versus 66 +/- 4 pg/ml) and IL-13 (1,226 +/- 279 versus 475 +/-
      65 pg/ml) in lung supernatants than mice sensitized with ovalbumin alone (OVA
      mice), while levels of IL-4 and serum IgE were not different. Lung mRNA
      expression of the C-C chemokine MCP-1 was increased in OVA-indomethacin mice,
      while there was no difference between the two groups in lung mRNA expression of
      eotaxin, MIP-1alpha, MIP-1beta, or MIP-2. Histologic examination revealed greater
      pulmonary interstitial eosinophilia in OVA-indomethacin mice as well. Contrary to
      our expectations, we conclude that in the BALB/c mouse, cyclooxygenase inhibition
      during allergen sensitization increases AHR, production of IL-5 and IL-13, and
      interstitial eosinophilia.

PMID- 10934106
TI  - Sleep architecture and respiratory disturbances in children with obstructive
      sleep apnea.
AB  - Little is known regarding sleep architecture in children with the obstructive
      sleep apnea syndrome (OSAS). We hypothesized that sleep architecture was normal,
      and that apnea increased over the course of the night, in children with OSAS. We
      analyzed polysomnographic studies from 20 children with OSAS and 10 control
      subjects. Sleep architecture was similar between the groups. Of obstructive
      apneas 55% occurred during rapid eye movement (REM) sleep. The apnea index, apnea
      duration, and degree of desaturation were greater during REM than non-REM sleep.
      OSAS data from the first and third periods of the night (periods A and C) were
      compared. Both the overall and the REM apnea index increased between periods A
      and C (11 to 25/h, p < 0.02; and 24 to 51/h, p < 0.01, respectively). There was
      no difference in Sa(O(2)) over time. Spontaneous arousals, but not respiratory
      related arousals, were more frequent during non-REM than REM sleep; these did not
      change from periods A to C. We conclude that children with OSAS have normal sleep
      stage distribution. OSAS is predominantly a REM phenomenon in children.
      Obstructive apnea worsens over the course of the night, independent of the
      changing amounts of REM sleep. We speculate that this increase in apnea severity
      may be secondary to upper airway muscle fatigue, changes in upper airway
      neuromotor control, or changes in REM density.

PMID- 10934107
TI  - Human isolated bronchial smooth muscle contains functional ryanodine/caffeine
      sensitive Ca-release channels.
AB  - Human bronchial smooth muscle (HBSM) contraction is implicated in a variety of
      respiratory diseases, including asthma. Yet, the presence of an operative calcium
      induced calcium release (CICR) mechanism, identified in various smooth muscles,
      has not been established in HBSM. We therefore studied Ca-releasing mechanisms in
      HBSM obtained at thoracotomy with special attention to ryanodine-sensitive
      receptor channels (RyRs). In freshly isolated bronchial myocytes, ryanodine (0.5
      to 50 microM) and caffeine (1 to 25 mM) induced transient increases in the
      cytoplasmic calcium concentration ([Ca(2+)](i)). Higher ryanodine concentrations
      (> 100 microM) inhibited the caffeine-induced [Ca(2+)](i) response, which was
      also blocked in the presence of tetracaine (300 microM) or ruthenium red (200
      microM), two potent CICR inhibitors. In HBSM strips, caffeine induced a transient
      contraction which, likewise, was inhibited by ryanodine and tetracaine. However,
      ryanodine (200 microM) modified neither the [Ca(2+)](i) response nor the
      contraction induced by K(+)-rich (110 mM) solution. Reverse
      transcriptase/polymerase chain reaction (RT-PCR) and RNase protection assay
      performed in HBSM have revealed the existence of mRNAs encoding only the type 3
      RyR. We also characterized acetylcholine-induced [Ca(2+)](i) and contractile
      responses. None of these responses was altered by ryanodine or by tetracaine.
      These results demonstrate, for the first time, the existence of functional RyRs
      in HBSM cells which, owing to the type of isoform or the amount of protein
      expressed, are not involved, under physiologic conditions, in depolarization- or
      agonist-induced contraction.

PMID- 10934108
TI  - The Fas/Fas-ligand system is not required for bleomycin-induced pulmonary
      fibrosis in mice.
AB  - Recent studies suggest that Fas-Fas-ligand (FasL) interactions play an important
      role in the development of lung injury and fibrosis. However, evidence to support
      this concept is still indirect. To determine whether Fas-FasL interaction is
      required for the development of bleomycin-induced pulmonary fibrosis in mice, we
      used Fas-deficient (lpr) and FasL-deficient (gld ) mice as animal models. After
      intratracheal instillation of bleomycin, we examined the lungs of mice through
      bronchoalveolar lavage, histologic studies, DNA nick-end labeling, and
      hydroxyproline assay. The development of cellular infiltrates, bronchiolar and
      alveolar epithelial apoptosis, and fibrosis following bleomycin instillation in
      the lungs in lpr mice and gld mice was similar to their development in wild-type
      mice. The results of this study show that bleomycin-induced pulmonary fibrosis
      does not require Fas-FasL interaction, and that epithelial cell apoptosis after
      bleomycin exposure is mediated by Fas-independent pathways.

PMID- 10934109
TI  - Increase in reactive nitrogen species production in chronic obstructive pulmonary
      disease airways.
AB  - Peroxynitrite, nitrogen dioxide, and other reactive nitrogen species (RNS) that
      are formed in the reaction of nitric oxide (NO) with superoxide anion, and in
      peroxidase-dependent mechanisms, have a potent inflammatory action. These
      molecules may therefore increase in number and have a role in inflammatory airway
      diseases. In the present study, we quantified RNS using immunostaining of
      nitrotyrosine and inducible NO synthase (iNOS) in airway inflammatory cells
      obtained by the induced sputum technique, and also quantified the exhaled NO
      concentration in subjects with chronic obstructive pulmonary disease (COPD),
      subjects with asthma, and healthy subjects (HS). Immunoreactivity for iNOS
      observed in the airway inflammatory cells was significantly and similarly higher
      in subjects with COPD and asthma than in HS, although exhaled NO levels were
      increased only in subjects with asthma. Inflammatory cells showed obvious
      nitrotyrosine immunoreactivity in subjects with COPD and to a lesser extent in
      those with asthma, but not in HS. There was a significant negative correlation
      between the percent predicted values of FEV(1) and the amount of nitrotyrosine
      formation in subjects with COPD, but not in those with asthma and HS. These
      results suggest that: (1) RNS may be involved in the pathobiology of the airway
      inflammatory and obstructive process in COPD; and (2) NO produced in the airways,
      presumably via iNOS, is consumed by its reaction with superoxide anion and/or
      peroxidase-dependent mechanisms.

PMID- 10934110
TI  - Enhanced expression of hepatocyte growth factor by pulmonary ischemia-reperfusion
      injury in the rat.
AB  - Hepatocyte growth factor (HGF) has recently been noted to function as a
      pulmotrophic factor for lung regeneration. The present study was conducted to
      determine if HGF would be induced in a rat model of pulmonary ischemia
      reperfusion (IR) injury, which was established by occlusion of the left lung, and
      to examine the significance of HGF in subsequent lung repair. The sham-operated
      rats underwent simple thoracotomy in which the lung was not clamped. We measured
      the plasma and the tissue levels of HGF by enzyme-linked immunosorbent assays,
      and the expression of HGF mRNA by Northern blotting. The plasma HGF level was
      markedly elevated after pulmonary ischemia and reached the peak value on the
      third postoperative day, being 5-fold higher than that of the sham-operated rats.
      HGF mRNA expression and the tissue HGF levels were augmented twofold in the
      ischemic reperfused lung. Immunohistochemical analysis revealed that the
      infiltrating alveolar macrophages were intensely stained for HGF. DNA synthesis
      of alveolar epithelial cells, as identified by proliferating cell nuclear antigen
      (PCNA) staining, was 3-fold higher in the reperfused lung than in the sham
      operated lung. Notably, HGF-neutralizing treatment with an anti-HGF antibody
      reduced DNA synthesis of alveolar epithelial cells in the reperfused lung and
      aggravated lung injury. This study shows that HGF was induced in the ischemic
      reperfused lung and may play an important role in regeneration of an injured lung
      after pulmonary IR.

PMID- 10934111
TI  - Evaluating the role of inducible nitric oxide synthase using a novel and
      selective inducible nitric oxide synthase inhibitor in septic lung injury
      produced by cecal ligation and puncture.
AB  - We studied the role of inducible nitric oxide synthase (iNOS) in septic lung
      injury using a novel and selective iNOS inhibitor (a fused piperidine derivative;
      ONO-1714) following a cecal ligation and puncture (CLP) procedure. All rats that
      received CLP died within 48 h after the intervention. The subcutaneous injection
      of ONO-1714 at 0.03 mg/kg every 12 h resulted in a significantly longer survival
      time than the saline control only when administration was started 12 h after the
      CLP procedure. The other administration schedules, which started immediately or 6
      h after the intervention, did not show any improvement in the survival rates in
      comparison with the saline control. The administration of ONO-1714 at higher (0.1
      mg/ kg) or lower (0.01 mg/kg) doses when given anytime after the intervention did
      not improve the survival rates. The NO(x) (NO(2)(-) + NO(3)(-)) levels in the
      plasma significantly increased 12 h after intervention in comparison with NO(x)
      at 0 h and thereafter further increased in parallel with the time elapsed. The
      CLP rats that were initially treated with ONO-1714 (0.03 mg/kg subcutaneously
      every 12 h) 12 h after intervention showed significantly reduced NO(x) levels in
      the plasma in comparison with the saline control. The NO synthase activity in
      lung homogenates increased from 6 to 24 h after the CLP and thereafter decreased
      to 42 h. The administration of ONO-1714 inhibited iNOS activity (under calcium
      free conditions) in preference to total iNOS activity (under calcium-dependent
      conditions) in lung homogenates, which thus suggested that this compound
      selectively inhibited iNOS in lung tissue. The iNOS protein expression in the
      lung and liver homogenates showed a similar time course with alterations of NOS
      activity, namely a maximum level at 24 h after the intervention followed by
      decreasing levels to 42 h. On the other hand, other isozymes of NOS, eNOS, and
      nNOS in lung homogenates, were constantly expressed over the time course after
      the CLP. Since the iNOS mRNA expression in lung homogenates continued to elevate
      until 42 h, the decrease in iNOS activity and protein expression later than 24 h
      after the CLP was thus considered to be due to some posttranscriptional mechanism
      during the late phase of sepsis. In conclusion, intervention with a potent and
      selective iNOS inhibitor seemed to improve survival in CLP rats when used at the
      appropriate doses and time points. However, the self-limited mechanism of iNOS
      regulation in the lungs may also indicate that iNOS plays only a limited role in
      sepsis and septic shock.

PMID- 10934112
TI  - Monocyte chemoattractant protein (MCP)-4 expression in the airways of patients
      with asthma. Induction in epithelial cells and mononuclear cells by
      proinflammatory cytokines.
AB  - Chemokines are chemotactic cytokines that play an important role in recruiting
      leukocytes in allergic inflammation. Monocyte chemoacctractant protein (MCP)-4 is
      a CC chemokine with potent chemotactic activities for eosinophils, monocytes, T
      lymphocytes, and basophils and therefore represents a good candidate to
      participate in allergic reactions. To determine if MCP-4 plays a role in asthma,
      we have investigated the expression of MCP-4 messenger RNA (mRNA) and protein in
      the airways of patients with asthma and normal control subjects by in situ
      hybridization and immunohistochemistry. We found that MCP-4 mRNA and protein was
      significantly upregulated in the epithelium and submucosa of bronchial biopsies
      and in the bronchoalveolar lavage (BAL) cells of patients with asthma compared
      with normal control subjects (p < 0. 01). In addition, MCP-4 protein was
      significantly elevated in the BAL fluid of patients with atopic asthma when
      compared with normal control subjects (p < 0.01) and there was a significant
      correlation between MCP-4, eotaxin, and eosinophils. In support of our in situ
      findings demonstrating MCP-4 expression in epithelial cells and mononuclear cells
      in vivo, we have found that MCP-4 expression can be induced in these cells in
      vitro by tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta). Interferon-gamma (IFN-gamma) acted synergistically with TNF-alpha and IL
      1beta in the induction of mRNA MCP-4 mRNA expression in A549 cells, whereas the
      glucocorticoid dexamethasone diminished the cytokine-induced expression of MCP-4.
      Our findings demonstrate that MCP-4 is upregulated in the airways of patients
      with asthma and suggest that MCP-4 plays a role in the recruitment of eosinophils
      into the airways of patients with asthma.

PMID- 10934113
TI  - Vitronectin protects alveolar macrophages from silica toxicity.
AB  - Silicosis is an interstitial lung disease caused by the inhalation of crystalline
      silicon dioxide. Current concepts suggest that a crucial step in the development
      of silicosis is silica-induced injury of alveolar macrophages (AM). The adhesive
      protein vitronectin is a natural constituent of the lung, in which its function
      is largely unexplored. This study investigated a possible role for vitronectin in
      protecting AM from silica exposure. In this study, the concentration of
      vitronectin was shown to be increased in the bronchoalveolar lavage fluid of
      silica-treated rats. Vitronectin affinity for silica was shown both in vitro and
      in vivo by immunostaining. Vitronectin reduced silica-induced injury to cultured
      AM as determined with the (51)Cr release assay. Vitronectin reduced silica
      induced free radical production as determined with a cell-free thiobarbituric
      acid assay. Additionally, vitronectin reduced the silica-induced respiratory
      burst in AM as determined with chemiluminescence. This study suggests that
      vitronectin may protect AM during the initial exposure to silica.

PMID- 10934114
TI  - Physical findings and the risk for obstructive sleep apnea. The importance of
      oropharyngeal structures.
AB  - In this study, we hypothesized that anatomic abnormalities of the oropharynx,
      particularly narrowing of the airway by the lateral pharyngeal walls, tonsils,
      and tongue, would be associated with an increased likelihood for obstructive
      apnea among patients presenting to a sleep disorders center. To test this
      hypothesis, we used data from a cohort of 420 patients presenting to the Penn
      Center for Sleep Disorders. Associations between individual variables in the
      clinical evaluation model and sleep apnea as defined by a respiratory disturbance
      index greater than or equal to 15 events per hour were characterized by odds
      ratios (ORs) with 95% confidence intervals (CIs). Multivariable logistic
      regression was used to simultaneously estimate ORs for multiple variables and to
      control for other relevant patient characteristics. Results showed that narrowing
      of the airway by the lateral pharyngeal walls (OR = 2.5; 95% CI, 1.6-3.9) had the
      highest association with obstructive sleep apnea (OSA) followed by tonsillar
      enlargement (OR = 2.0; 95% CI, 1.0-3.8), enlargement of the uvula (OR = 1.9; 95%
      CI, 1.2-2.9), and tongue enlargement (OR = 1.8; 95% CI, 1.0-3.1). Low-lying
      palate, retrognathia, and overjet were not found to be significantly associated
      with OSA. Controlling for BMI and neck circumference, only lateral narrowing and
      enlargement of the tonsils maintained their significant (OR = 2.0 and 2.6,
      respectively). A subgroup analysis examining differences between male and female
      subjects showed that no oropharyngeal risk factor achieved significance in women
      while lateral narrowing was the sole independent risk factor in men. These
      findings suggest that enlargement of the oropharyngeal soft tissue structures,
      particularly the lateral pharyngeal walls, is associated with an increased
      likelihood of OSA among patients presenting to sleep disorders centers.

PMID- 10934115
TI  - Pulmonary lymphangioleiomyomatosis in a man.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disease reported to occur
      exclusively in women. We describe a phenotypically normal man with pulmonary LAM.
      Fluorescence in situ hybridization (FISH) studies performed on the lung biopsy
      confirmed a normal XY genotype. Our patient also had stigmata of tuberous
      sclerosis complex (TSC), including facial angiofibromas and renal angiomyolipoma.
      Immunohistochemical stains of both LAM and renal angiomyolipoma showed positive
      immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin
      (TSC2). Loss of heterozygosity (LOH) for TSC2 was further demonstrated in the
      renal angiomyolipoma. Coupled with the results of immunostains, these findings
      are consistent with TSC2 mutation.

PMID- 10934116
TI  - Varicella-zoster virus detection by polymerase chain reaction using
      bronchoalveolar lavage specimens.
AB  - We report the use of polymerase chain reaction (PCR) techniques from a
      bronchoalveolar lavage (BAL) specimen for the successful early diagnosis in a
      case of atypical but severe varicella-zoster virus (VZV) pneumonitis. Atypical
      presentations of disseminated VZV frequently prolong the time required for
      accurate diagnosis, resulting in increased morbidity, or mortality. Although
      further investigation is necessary to determine the sensitivity and positive
      predictive value of this test, PCR analysis of bronchoscopic specimens may
      expedite the diagnosis of disseminated VZV.

PMID- 10934118
TI  - Familial aggregation and segregation analysis of eosinophil levels.

PMID- 10934117
TI  - Increased risk of fibrosing alveolitis associated with interleukin-1 receptor
      antagonist and tumor necrosis factor-alpha gene polymorphisms.
AB  - Fibrosing alveolitis (FA) is characterized by persistent inflammation and
      elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1
      beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung.
      Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position
      -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic
      inflammatory disease populations. We have tested the hypothesis that
      predisposition to FA may also be influenced by these polymorphisms by genotyping
      88 cases and matched controls from England and 61 cases and 103 unmatched
      controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele
      2 in each case. For IL-1RN allele 2, in the English group, the relative odds of
      FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95%
      confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of
      1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA
      was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p
      = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of
      TNF-A allele 2 was also associated with increased risk of FA in the English (OR,
      1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to
      5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF
      A (-308) allele 2 confer increased risk of developing FA and, therefore, that
      unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in
      this condition.

PMID- 10934119
TI  - Vitamin D receptor gene polymorphism in patients with sarcoidosis.

PMID- 10934120
TI  - Acute respiratory failure in patients with severe community-acquired pneumonia: a
      prospective randomized evaluation of noninvasive ventilation.

PMID- 10934121
TI  - Measurement of airway inflammation in children. Introduction.

PMID- 10934122
TI  - The concept of airway inflammation.

PMID- 10934123
TI  - The role of inflammation in airway disease: remodeling.

PMID- 10934124
TI  - Clinical implications of inflammation in young children.

PMID- 10934125
TI  - Bronchoalveolar lavage and tracheal aspirate for assessing airway inflammation in
      children.

PMID- 10934126
TI  - Brush biopsy and mucosal biopsy.

PMID- 10934127
TI  - Gas analysis.

PMID- 10934128
TI  - Upper airway sampling.

PMID- 10934130
TI  - Statistical/design methods.

PMID- 10934129
TI  - Sampling methods: urine/blood analysis.

PMID- 10934131
TI  - Immunopathology of allergy and asthma in childhood.

PMID- 10934132
TI  - Protective and harmful effects of viral infections in childhood on wheezing
      disorders and asthma.

PMID- 10934133
TI  - Environmental air pollution.

PMID- 10934134
TI  - Inflammatory markers in clinical practice.

PMID- 10934135
TI  - Developmental airway cell biology. The "normal" young child.

PMID- 10934136
TI  - Context dependency of markers of disease.

PMID- 10934137
TI  - Aberrant ALK tyrosine kinase signaling. Different cellular lineages, common
      oncogenic mechanisms.

PMID- 10934138
TI  - Germline and somatic mutation analysis of MLH3 in MSI-positive colorectal cancer.
AB  - Microsatellite instability (MSI) is characteristic of hereditary nonpolyposis
      colorectal cancer, and occurs in a subset (10 to 15%) of unselected colorectal
      cancer cases. In hereditary nonpolyposis colorectal cancer, MSI is caused by
      defects in five mismatch repair genes, and in sporadic cases the main cause seems
      to be somatic MLH1 promoter methylation. Most likely additional hereditary
      nonpolyposis colorectal cancer genes remain to be discovered. Genes with simple
      repeats in their coding region are often targets for deletions in MSI-positive
      tumors. Several genes (TGFbeta RII, IGFIIR, MSH3, MSH6, BAX, MBD4) with
      significance in tumorigenesis harbor repeats in their coding regions and are
      often somatically inactivated because of deletions causing frameshifts. Recently,
      a novel human mismatch repair gene, MLH3, was cloned and shown to be involved in
      mammalian mismatch repair. To evaluate the possible role of MLH3 in hereditary
      cancer, we performed germline single-strand conformation polymorphism-analysis
      for 52 patients displaying features of inherited colorectal cancer. Forty-six of
      these had been diagnosed with MSI-positive tumors. No germline mutations were
      found. Similar to MSH3 and MSH6, MLH3 harbors mononucleotide repeats, ie, (A(6))
      (A(9)), in its coding region, which makes it a putative target for somatic
      mutations in MSI-positive tumors. To evaluate its somatic inactivation we
      performed a deletion search focusing on eight exonic MLH3 mononucleotide repeats
      in a series of 93 MSI-positive tumors. Somatic deletions were found in 8.6% of
      the samples, a frequency similar to one detected in neutral noncoding
      mononucleotide repeats. No evidence of involvement of MLH3 in MSI tumorigenesis
      was obtained.

PMID- 10934139
TI  - Losses of chromosomes 1p and 3q are early genetic events in the development of
      sporadic pheochromocytomas.
AB  - Despite several loss of heterozygosity studies, a comprehensive genomic survey of
      pheochromocytomas is still lacking. To identify DNA copy number changes which
      might be important in tumor development and progression and which may have
      diagnostic utility, we evaluated genetic aberrations in 29 sporadic adrenal and
      extra-adrenal pheochromocytomas (19 clinically benign tumors and 10 malignant
      lesions). Comparative genomic hybridization was performed using directly
      fluorochrome-conjugated DNA extracted from frozen (16) and paraffin-embedded (13)
      tumor tissues. The most frequently observed changes were losses of chromosomes
      1p11-p32 (86%), 3q (52%), 6q (34%), 3p, 17p (31% each), 11q (28%), and gains of
      chromosomes 9q (38%) and 17q (31%). No amplification was identified and no
      difference between adrenal and extra-adrenal tumors was detected. Progression to
      malignant tumors was strongly associated with deletions of chromosome 6q (60%
      versus 21% in clinically benign lesions, P = 0.0368) and 17p (50% versus 21%).
      Fluorescence in situ hybridization confirmed the comparative genomic
      hybridization data of chromosomes 1p, 3q, and 6q, and revealed aneuploidy in some
      tumors. Our results suggest that the development of pheochromocytomas is
      associated with specific genomic aberrations, such as losses of 1p, 3q, and 6q
      and gains of 9q and 17q. In particular, tumor suppressor genes on chromosomes 1p
      and 3q may be involved in early tumorigenesis, and deletions of chromosomes 6q
      and 17p in progression to malignancy.

PMID- 10934140
TI  - Neurodegeneration with brain iron accumulation, type 1 is characterized by alpha
      , beta-, and gamma-synuclein neuropathology.
AB  - Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden
      Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by
      Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar
      ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in
      the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological
      lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal
      inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here
      we show that there is an accumulation of alpha-synuclein (alphaS) in LB-like
      inclusions, glial inclusions, and spheroids in the brains of three NBIA 1
      patients. Further, beta-synuclein (betaS) and gamma-synuclein (gammaS)
      immunoreactivity was detected in spheroids but not in LB-like or glial
      inclusions. Western blot analysis demonstrated high-molecular weight alphaS
      aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl
      sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of alphaS
      were markedly reduced in the Triton X-100-soluble fractions compared to control
      brain, and unlike other synucleinopathies, insoluble alphaS did not accumulate in
      the formic acid-soluble fraction. These findings expand the concept of
      neurodegenerative synucleinopathies by implicating alphaS, betaS, and gammaS in
      the pathogenesis of NBIA 1.

PMID- 10934141
TI  - Genetic imbalances with impact on survival in head and neck cancer patients.
AB  - Chromosomal imbalances in 113 primary head and neck squamous cell carcinomas
      (HNSCCs) determined by comparative genomic hybridization were correlated with
      patients survival using custom-made computer software which enabled the
      assessment of individual chromosomal loci. The Kaplan-Meier analysis revealed
      that overrepresentations of 2q12, 3q21-29, 6p21.1, 11q13, 14q23, 14q24, 14q31,
      14q32, 15q24, 16q22, and deletions of 8p21-22 and 18q11.2 were significantly
      associated with both shorter disease-free interval and disease-specific survival
      in this tumor collective. Multivariate Cox proportional hazards regression models
      consistently identified the gains of 3q21-29, 11q13, and the loss of 8p21-22 as
      independent prognostic markers carrying a higher significance than the nodal
      status as the only clinicopathological parameter with statistical importance. In
      addition, these three markers allowed a molecular dissection of the patients with
      low clinical risk (pN0 and pT2 tumors). Thus, the genomic data being derived from
      the evaluation of primary HNSCC enabled a stratification of the patients into
      subgroups with different survival highlighting the necessity of a genetically
      based tumor classification for refining diagnosis and treatment of HNSCC
      patients.

PMID- 10934142
TI  - TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors.
AB  - Inflammatory myofibroblastic tumors (IMTs) are neoplastic mesenchymal
      proliferations featuring an inflammatory infiltrate composed primarily of
      lymphocytes and plasma cells. The myofibroblastic cells in some IMTs contain
      chromosomal rearrangements involving the ALK receptor tyrosine-kinase locus
      region (chromosome band 2p23). ALK-which is normally restricted in its expression
      to neural tissues-is expressed strikingly in the IMT cells with 2p23
      rearrangements. We now report a recurrent oncogenic mechanism, in IMTs, in which
      tropomyosin (TPM) N-terminal coiled-coil domains are fused to the ALK C-terminal
      kinase domain. We have cloned two ALK fusion genes, TPM4-ALK and TPM3-ALK, which
      encode approximately 95-kd fusion oncoproteins characterized by constitutive
      kinase activity and tyrosylphosphorylation. Immunohistochemical and molecular
      correlations, in other IMTs, implicate non-TPM ALK oncoproteins that are
      predominantly cytoplasmic or pre- dominantly nuclear, presumably depending on the
      subcellular localization of the ALK fusion partner. Notably, a TPM3-ALK oncogene
      was reported recently in anaplastic lymphoma, and TPM3-ALK is thereby the first
      known fusion oncogene that transforms, in vivo, both mesenchymal and lymphoid
      human cell lineages.

PMID- 10934143
TI  - Colorectal carcinomas arising in the hyperplastic polyposis syndrome progress
      through the chromosomal instability pathway.
AB  - The hyperplastic polyposis syndrome is characterized by the presence within the
      colon of multiple large hyperplastic polyps. We describe a case of hyperplastic
      polyposis syndrome associated with two synchronous carcinomas, one of which
      arises within a pre-existing hyperplastic lesion. Comparative genomic
      hybridization was used to determine genetic changes in both carcinomas and
      several associated hyperplastic lesions. Microsatellite analysis at five loci was
      performed on carcinomas and representative hyperplastic polyps, and p53 status
      was analyzed by immunohistochemistry. Both carcinomas showed multiple genetic
      aberrations, including high level gains of 8q and 13q, and loss of 5q. These
      changes were not seen in the hyperplastic polyps. Microsatellite instability was
      not seen in the carcinomas, four separate hyperplastic polyps, the hyperplastic
      polyp with mild adenomatous change associated with the carcinoma, or a separate
      serrated adenoma. Allelic imbalance in the cancers at D5S346 and D17S938
      suggested allelic loss of both p53 and APC, as well as at the loci D13S263,
      D13S174, D13S159, and D18S49. An early invasive carcinoma in one hyperplastic
      polyp stained for p53 protein, but the associated hyperplastic polyp was
      negative. In this case, neoplastic progression followed the typical genetic
      pathway of common colorectal carcinoma and occurred synchronously with mutation
      of p53.

PMID- 10934144
TI  - Overexpression of clusterin in human breast carcinoma.
AB  - Clusterin has been implicated in numerous processes including active cell death,
      immune regulation, cell adhesion and morphological transformation. The purpose of
      this study was to examine clusterin expression in a large series of breast
      carcinomas by immunohistochemistry and in situ hybridization. The study included
      40 samples of non-neoplastic glandular epithelia, 42 benign lesions, 15 atypical
      intraductal hyperplasias, 35 carcinomas in situ, 114 invasive carcinomas, and
      lymph node metastases from 40 patients. Epithelial normal cells were always
      negative for clusterin expression and only 19% of the benign lesions presented
      positive staining. In contrast to the benign lesions, however, the frequency of
      clusterin positive samples increased in atypical hyperplasias (47%, P = 0.08),
      intraductal carcinomas (49%, P = 0.01) and invasive carcinomas (53%, P < 0.001).
      Positive staining presented a cytoplasmic pattern, except in 3 cases of invasive
      carcinomas which had nuclear staining. Clusterin mRNA by in situ hybridization
      confirmed the specific cellular pattern of clusterin expression by
      immunohistochemistry. Clusterin expression was associated with large tumor size
      (P = 0.04), estrogen and progesterone receptor negative status (P = 0.02 and P =
      0.001, respectively) and with the progression from primary carcinoma to
      metastatic carcinoma in lymph nodes (80% metastatic nodes had positive
      expression) (P = 0.004). Ten of 15 (67%) primary carcinomas without clusterin
      expression became positive in lymph node metastases, while most (22 of 25, 88%)
      of the clusterin-positive primary carcinomas were also immunoreactive in
      metastases. In survival analysis, clusterin expression did not represent a
      prognostic indicator by uni- or multivariate analysis. The increased clusterin
      expression in breast carcinomas tended to correlate inversely with the apoptotic
      index (P = 0.09) which indicates that clusterin gene expression is not a
      prerequisite to cellular death by apoptosis. From these results, we suggest that
      clusterin may have a role in tumorigenesis and progression of human breast
      carcinomas.

PMID- 10934145
TI  - alpha-synuclein promotes mitochondrial deficit and oxidative stress.
AB  - Abnormal accumulation of the presynaptic protein alpha-synuclein has recently
      been implicated in the pathogenesis of Alzheimer's and Parkinson's diseases.
      Because neurodegeneration in these conditions might be associated with
      mitochondrial dysfunction and oxidative stress, the effects of alpha-synuclein
      were investigated in a hypothalamic neuronal cell line (GT1-7). alpha-Synuclein
      overexpression in these cells resulted in formation of alpha-synuclein
      immunopositive inclusion-like structures and mitochondrial alterations
      accompanied by increased levels of free radicals and decreased secretion of
      gonadotropin-releasing hormone. These alterations were ameliorated by
      pretreatment with anti-oxidants such as vitamin E. Taken together these results
      suggest that abnormal accumulation of alpha-synuclein could lead to mitochondrial
      alterations that may result in oxidative stress and, eventually, cell death.

PMID- 10934146
TI  - The expression and distribution of the hypoxia-inducible factors HIF-1alpha and
      HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages.
AB  - The cellular response to hypoxia includes the hypoxia-inducible factor-1 (HIF-1)
      induced transcription of genes involved in diverse processes such as glycolysis
      and angiogenesis. Induction of the HIF-regulated genes, as a consequence of the
      microenvironment or genetic changes, is known to have an important role in the
      growth of experimental tumors. Hypoxia-inducible factors 1alpha and 2alpha (HIF
      1alpha and HIF-2alpha) are known to dimerize with the aryl hydrocarbon receptor
      nuclear translocator in mediating this response. Because regulation of the alpha
      chain protein level is a primary determinant of HIF activity, our aim was to
      investigate the distribution of HIF-1alpha and HIF-2alpha by immunohistochemistry
      in normal and pathological tissues using monoclonal antibodies (mAb). We raised a
      new mAb to detect HIF-1alpha, designated 122, and used our previously validated
      mAb 190b to HIF-2alpha. In the majority of solid tumors examined, including
      bladder, brain, breast, colon, ovarian, pancreatic, prostate, and renal
      carcinomas, nuclear expression of HIF-1alpha and -2alpha was observed in varying
      subsets of the tumor cells. HIF-2alpha was also strongly expressed by subsets of
      tumor-associated macrophages, sometimes in the absence of any tumor cell
      expression. Less frequently staining was observed in other stromal cells within
      the tumors and in normal tissue adjacent to tumor margins. In contrast, in normal
      tissue neither molecule was detectable except within subsets of bone marrow
      macrophages, where HIF-2alpha was strongly expressed.

PMID- 10934147
TI  - Differential expression of fibromodulin, a transforming growth factor-beta
      modulator, in fetal skin development and scarless repair.
AB  - Transforming growth factor-beta (TGF-beta1, -beta2, and -beta3) has been
      implicated in the ontogenetic transition from scarless fetal repair to adult
      repair with scar. Generally, TGF-beta exerts its effects through type I and II
      receptors; however, TGF-beta modulators such as latent TGF-beta binding protein-1
      (LTBP-1), decorin, biglycan, and fibromodulin can bind and potentially inhibit
      TGF-beta activity. To more fully explore the role of TGF-beta ligands, receptors,
      and potential modulators during skin development and wound healing, we have used
      a rat model that transitions from scarless fetal-type repair to adult-type repair
      with scar between days 16 and 18 of gestation. We showed that TGF-beta ligand and
      receptor mRNA levels did not increase during the transition to adult-type repair
      in fetal skin, whereas LTBP-1 and fibromodulin expression decreased. In addition,
      TGF-beta1 and -beta3; type I, II, and III receptors; as well as LTBP-1, decorin,
      and biglycan were up-regulated during adult wound healing. In marked contrast,
      fibromodulin expression was initially down-regulated in adult repair.
      Immunostaining demonstrated significant fibromodulin induction 36 hours after
      injury in gestation day 16, but not day 19, fetal wounds. This inverse
      relationship between fibromodulin expression and scarring in both fetal and adult
      rat wound repair suggests that fibromodulin may be a biologically relevant
      modulator of TGF-beta activity during scar formation.

PMID- 10934148
TI  - Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.
AB  - Osteoprotegerin ligand (OPGL) targets osteoclast precursors and osteoclasts to
      enhance differentiation and activation, however, little is known about OPGL
      effects on osteoclast survival. In vitro, the combination of OPGL + colony
      stimulating factor-1 (CSF-1) is required for optimal osteoclast survival.
      Ultrastructurally, apoptotic changes were observed in detached cells and culture
      lysates exhibited elevated caspase 3 activity, particularly in cultures lacking
      CSF-1. DEVD-FMK (caspase 3 inhibitor) partially protected cells when combined
      with OPGL, but not when used alone or in combination with CSF-1. CSF-1 maintained
      NF-kappaB activation and increased the expression of bcl-2 and bcl-X(L) mRNA, but
      had no effect on JNK activation. In contrast, OPGL enhanced both NF-kappaB and
      JNK kinase activation and increased the expression of c-src, but not bcl-2 and
      bcl-X(L) mRNA. These data suggest that aspects of both OPGL's and CSF-1's
      signaling/survival pathways are required for optimal osteoclast survival. In
      mice, a single dose of OPG, the OPGL decoy receptor, led to a >90% loss of
      osteoclasts because of apoptosis within 48 hours of exposure without impacting
      osteoclast precursor cells. Therefore, OPGL is essential, but not sufficient, for
      osteoclast survival and endogenous CSF-1 levels are insufficient to maintain
      osteoclast viability in the absence of OPGL.

PMID- 10934149
TI  - The proapoptotic BH3-only protein bim is expressed in hematopoietic, epithelial,
      neuronal, and germ cells.
AB  - Proapoptotic Bcl-2 family members activate cell death by neutralizing their anti
      apoptotic relatives, which in turn maintain cell viability by regulating the
      activation of the cell death effectors, the caspases. Bim belongs to a distinct
      subgroup of proapoptotic proteins that only resemble other Bcl-2 family members
      within the short BH3 domain. Gene targeting experiments in mice have shown that
      Bim is essential for the execution of some but not all apoptotic stimuli, for
      hematopoietic cell homeostasis, and as a barrier against autoimmunity. There are
      three Bim isoforms, Bim(S), Bim(L), and Bim(EL), which have different
      proapoptotic potencies due at least in part to differences in interaction with
      the dynein motor complex. The expression pattern of Bim was investigated by
      immunohistochemical staining, immunoprecipitation followed by Western blotting,
      and in situ hybridization. Bim was found in hematopoietic, epithelial, neuronal,
      and germ cells. Bim(L) and Bim(EL) were coexpressed at similar levels in many
      cell types, but Bim(S) was not detected. Microscopic examination revealed a
      punctate pattern of Bim(L) and Bim(EL) immunostaining, indicating association
      with cytoplasmic structures. These results are discussed in the context of the
      phenotype of Bim-deficient mice and the post-translational regulation of Bim's
      pro-apoptotic activity.

PMID- 10934150
TI  - In vivo detection of vascular adhesion protein-1 in experimental inflammation.
AB  - Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial
      glycoprotein which mediates leukocyte-endothelial cell interactions. To study the
      pathogenetic significance of VAP-1 in inflammatory disorders, an in vivo
      immunodetection method was used to detect the regulation of luminally expressed
      VAP-1 in experimental skin and joint inflammation in the pig and dog. Moreover,
      VAP-1 was studied as a potential target to localize inflammation by
      radioimmunoscintigraphy. Up-regulation of VAP-1 in experimental dermatitis and
      arthritis could be visualized by specifically targeted immunoscintigraphy.
      Moreover, the translocation of VAP-1 to the functional position on the
      endothelial surface was only seen in inflamed tissues. These results suggest that
      VAP-1 is both an optimal candidate for anti-adhesive therapy and a potential
      target molecule for imaging inflammation.

PMID- 10934151
TI  - Association of B7-1 co-stimulation with the development of graft arterial
      disease. Studies using mice lacking B7-1, B7-2, or B7-1/B7-2.
AB  - To investigate the roles of B7-1 and/or B7-2 co-stimulatory molecule in the
      development of graft arterial disease (GAD), major histocompatibility complex
      (MHC) class II-mismatched allograft hearts were transplanted into wild-type, B7
      1(-/-), B7-2(-/-), or B7-1/B7-2(-/-) recipient mice. Grafts were explanted at 4
      or 8 weeks and used for histological and immunohistochemical analyses, RNase
      protection assay, and flow cytometry of graft infiltrating cells. Grafts in wild
      type recipients showed macrophage, recipient MHC class II, and B7 molecule co
      localization by immunohistochemistry to GAD lesions. Flow cytometry revealed that
      CD11b(+) and MHC class II(+) graft infiltrating cells expressed B7-1 more than B7
      2, whereas B7-2 expression was predominant in CD11b(-) cells at 4 and 8 weeks.
      GAD was significantly attenuated in the allografts in B7-1(-/-) and B7-1/B7-2(-/
      ) but not in B7-2(-/-) recipients compared to wild-type hosts. Interferon-gamma
      mRNA levels were comparable in all graft combinations, whereas interleukin-4 mRNA
      levels decreased in grafts in B7-2 deficient hosts, but did not correlate with
      GAD attenuation. The findings indicate distinct roles for B7-1 and B7-2 co
      stimulatory molecules in the development of GAD, potentially because of
      differential expression of B7-1 and B7-2 molecules on distinct stimulator and/or
      effector cell populations.

PMID- 10934152
TI  - Differential effects of simian immunodeficiency virus infection on immune
      inductive and effector sites in the rectal mucosa of rhesus macaques.
AB  - The rectal mucosa, a region involved in human immunodeficiency virus/simian
      immunodeficiency virus (SIV) infection and transmission, contains immune
      inductive sites, rectal lymphoid nodules (RLN), and effector sites, the lamina
      propria (LP). This study was designed to evaluate cell populations involved in
      rectal mucosal immune function in both RLN and LP, by immunocytochemical analysis
      of rectal mucosa from 11 SIV-infected (2 to 21 months postinfection) and five
      naive rhesus macaques. In the rectum, as previously observed in other intestinal
      regions, CD4(+) cells were dramatically reduced in the LP of SIV-infected
      macaques, but high numbers of CD4(+) cells remained in RLN indicating maintenance
      of T cell help in inductive sites. Cells expressing the mucosal homing receptor
      alpha4beta7 were dramatically decreased in the RLN and LP of most SIV-infected
      macaques. The RLN of both naive and SIV-infected macaques contained high numbers
      of CD68 + MHC-II+ macrophages and cells expressing the co-stimulatory molecules
      B7-2 and CD40, as well as IgM + MHCII+ and IgM + CD40+ B cells, indicating
      maintenance of antigen presentation capacity. The LP of all three macaques SIV
      infected for 2 months contained many B7-2+ cells, suggesting increased activation
      of antigen-presenting cells. LP of SIV-infected rectal mucosa contained increased
      numbers of IgM+ cells, confirming previous observations in small intestine and
      colon. The data suggest that antigen-presentation capacity is maintained in
      inductive sites of SIV-infected rectal mucosa, but immune effector functions may
      be altered.

PMID- 10934154
TI  - Comparison of the T cell patterns in leprous and cutaneous sarcoid granulomas.
      Presence of Valpha24-invariant natural killer T cells in T-cell-reactive leprosy
      together with a highly biased T cell receptor Valpha repertoire.
AB  - The T-cell-reactive (eg, tuberculoid and reversal) forms of leprosy represent a
      well-defined granulomatous reaction pattern against an invading pathogen. The
      immune response in cutaneous sarcoidosis is a granulomatous condition that
      pathologically is very similar to T-cell reactive leprosy. However, it lacks a
      defined causative agent. In view of the role of NKT cells in murine granulomas
      induced by mycobacterial cell walls, we have searched for the presence of NKT
      cells in the cutaneous lesions of both leprosy and sarcoidosis. These cells were
      present in T-cell-reactive leprosy but were undetectable in cutaneous
      sarcoidosis. We have also studied the TCR Valpha repertoire in the two diseases.
      In addition to Valpha24(+) NKT cells, all patients with T-cell-reactive leprosy
      showed a very restricted T-cell-reactive Valpha repertoire with a strong bias
      toward the use of the Valpha6 and Valpha14 segments. Valpha6 and Valpha14(+) T
      cells were polyclonal in terms of CDR3 length and Jalpha usage. In contrast, most
      sarcoidosis patients showed a diverse usage of Valpha chains associated with
      clonal or oligoclonal expansions reminiscent of antigen-driven activation of
      conventional T cells. Thus the origin and perpetuation of the two kinds of
      granulomatous lesions appear to depend on altogether distinct T-cell recruiting
      mechanisms.

PMID- 10934153
TI  - Induction of cell-cycle regulators in simian immunodeficiency virus encephalitis.
AB  - Neuronal degeneration associated with human immunodeficiency virus encephalitis
      has been attributed to neurotoxicity of signaling molecules secreted by
      activated, infected macrophages. We hypothesized that the barrage of signals
      present in the extracellular milieu of human immunodeficiency virus-infiltrated
      brain causes inappropriate activation of neuronal cell-cycle machinery. We
      examined the presence of three members of the cell-cycle control machinery: pRb,
      E2F1, and p53 in the simian immunodeficiency virus encephalitis (SIVE) model.
      Compared to noninfected and simian immunodeficiency virus-infected,
      nonencephalitic controls, we observed increased protein expression of E2F1 and
      p53 and aberrant cellular localization of E2F1 and pRb. In SIVE, E2F1 was
      abundant in the cytoplasm of neurons in both neurons and astrocytes proximal to
      SIVE pathology in the basal ganglia. pRb staining was nuclear and cytoplasmic in
      cortical neurons of SIVE cases. Antibodies to phosphorylated pRb also labeled the
      cytoplasm of cortical neurons. These data suggest that in SIVE, cell signaling
      results in phosphorylation of pRb which may result in subsequent alteration in
      E2F1 activity. As increased E2F1 and p53 activities have been linked to cell
      death, these data suggest that the neurodegeneration in SIVE could in part be
      because of changes in expression and activity of cell-cycle machinery.

PMID- 10934155
TI  - Gelatinase B is required for alveolar bronchiolization after intratracheal
      bleomycin.
AB  - Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP
      9), has been described in the lungs in pulmonary fibrosis. Intratracheal
      bleomycin is often used experimentally to produce lesions resembling human
      fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced
      fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B
      deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin
      the two groups of mice were indistinguishable in terms of pulmonary histology and
      total lung collagen and elastin. However, the lungs of gelatinase B-deficient
      mice showed minimal alveolar bronchiolization, whereas bronchiolization was
      prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified
      immunohistochemically in terminal bronchiolar cells and bronchiolized cells 7 and
      14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA
      was increased at the same times. Many bronchiolized cells displayed Clara cell
      features by electron microscopy. Some bronchiolized cells stained with antibody
      to helix transcription factor 4, a factor associated with the ciliated cell
      phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin
      irrespective of gelatinase B. However, gelatinase B is required for alveolar
      bronchiolization, perhaps by facilitating migration of Clara cells and other
      bronchiolar cells into the regions of alveolar injury.

PMID- 10934156
TI  - Differential expression of the rat gamma-glutamyl transpeptidase gene promoters
      along with differentiation of hepatoblasts into biliary or hepatocytic lineage.
AB  - gamma-Glutamyl transpeptidase (GGT), a major enzyme of glutathione (GSH)
      homeostasis, is often used as a biliary marker to follow the differentiation of
      hepatic precursor cells. The expression of the GGT gene is driven by different
      promoters and yields multiple mRNAs, depending on the cell type or the stage of
      differentiation. In the present study, we analyzed the GGT mRNA expression
      pattern by quantitative reverse transcriptase-polymerase chain reaction or by in
      situ hybridization i) in the liver, in vivo, at early stages of development; ii)
      in oval cells, which proliferate and differentiate into hepatocytes in response
      to galactosamine injury in vivo; and finally, iii) during hepatoblast
      differentiation, in vitro. We show that GGT gene transcription originates from
      promoters P3, P4, and P5 in rat hepatic precursor cells. Differentiation of these
      cells induces profound alterations in GGT gene expression, leading to extinction
      of promoters P4 and P5, when they differentiate into the hepatocytic pathway, and
      to extinction of promoters P3 and P5 when they differentiate into the biliary
      pathway. This diversity in GGT mRNA expression provides unique molecular probes
      to follow hepatic precursor cell differentiation. Furthermore, the identification
      of factors governing GGT P5 and P4 promoter expression should provide further
      insight into the molecular events that occur as the liver precursor cell
      differentiates into the hepatic lineages.

PMID- 10934157
TI  - Liver damage using suicide genes. A model for oval cell activation.
AB  - Liver regeneration from the facultative hepatic stem cells, the oval cells, takes
      place in situations in which liver regeneration from pre-existing hepatocytes is
      prevented. Different models have been used to stimulate oval cell response. Many
      of them involve the use of carcinogenic agents with or without partial
      hepatectomy. In this study we show that adenovirus-mediated gene transfer of the
      suicide gene thymidine kinase followed by ganciclovir administration caused
      hepatotoxicity of variable intensity. Rats with moderate elevation in serum
      transaminases recovered normal liver architecture few weeks after adenovirus
      injection. In contrast, rats with severe liver damage exhibited a marked and
      persisting activation of oval cells accompanied by ductular hyperplasia. In some
      rats, such lesion eventually evolved to cholangiofibrosis and in one rat to
      cholangiocarcinoma. Deposition of fibronectin and increased number of hepatic
      stellate cells were found in association with oval cells and cholangiofibrotic
      lesions. Hepatocyte growth factor was hyperexpressed in the livers with intense
      oval cell response or ductular proliferation, suggesting a participation of this
      factor in those lesions. In summary, our data demonstrate activation of oval cell
      response after gene transfer of thymidine kinase followed by ganciclovir
      administration. These findings indicate that high doses of this therapy causes
      liver damage together with an impairment in hepatocellular regeneration.

PMID- 10934159
TI  - Characterization of genomic alterations in hepatoblastomas. A role for gains on
      chromosomes 8q and 20 as predictors of poor outcome.
AB  - As data on the genomic alterations in hepatoblastoma (HB) are limited, 34 HB
      tumors and three HB cell lines were screened for DNA copy number changes by
      comparative genomic hybridization. The average number of chromosomal imbalances
      per tumor was 2.3 +/- 0.5 (mean +/- SEM) with gains sevenfold more frequent than
      losses. The most frequent gains of chromosomal material in HB tumors were on 2q
      (44%), 1q (41%), 2p (29%), 20 (24%), 22q (18%), 8q (15%), 8p and 12q (9% each),
      as well as 7q, 12p, and 17 (6% each) and the only recurrent loss was on 4q in 12%
      of cases. Highly amplified sequences were identified in four tumors and mapped to
      2q24 in two cases, to 8q in two cases (once to 8q11.2-q13 and once to 8q11.2
      q21.3) as well as to 10q24-q26 in one case. In one cell line, highly amplified
      DNA sequences were mapped to 7p and 8q. Comparison to previously published data
      on this series of HB revealed that the number of chromosomal imbalances was
      significantly higher in HB tumors with loss of heterozygosity on 11p (P = 0.03),
      whereas in five of 10 HB biopsies without chromosomal imbalances, beta-catenin
      gene mutations were found. HB patients were divided into a good (no evidence of
      disease) and a poor (died of disease) outcome group according to their clinical
      course after standard therapy. Two alterations were found to be significantly
      associated with poor outcome: gain on 8q (P = 0.007) and gain on 20 (P = 0.009).
      In summary, our analysis allowed the identification of gains on chromosomes 1q
      and 2 as hallmark DNA copy number changes in HB with 2q24 as a critical
      chromosomal band. Furthermore, this study provided evidence that gains on 8q and
      20 play a role as markers of prognostic significance in HB.

PMID- 10934158
TI  - Cellular origin of regenerating parenchyma in a mouse model of severe hepatic
      injury.
AB  - Several treatments in rodents, including administration of the alkylating agent
      dipin, followed by two-thirds partial hepatectomy in mice combine destruction of
      liver parenchyma with hepatocyte mitoinhibition. These treatments induce
      proliferation of bile epithelial-like cells (termed oval cells), development of
      foci composed of small hepatocytes, and eventual replacement of damaged
      parenchyma by healthy hepatocytes. It has been proposed that these oval cells
      represent transitional cells in a nonhepatocytic liver facultative stem cell
      lineage that can give rise to the small hepatocyte foci, and that these foci
      eventually become confluent and replace liver parenchyma. In this study, we used
      in vivo cell lineage marking in genetically chimeric livers to test the
      hypothesis that hepatocytes can serve as the precursor cell type to the small
      hepatocyte foci that develop in mouse liver after treatment with dipin plus
      partial hepatectomy. Although we do not exclude the possibility that some small
      hepatocyte foci may be stem cell-derived, we demonstrate that hepatocyte-derived
      foci are present after dipin-induced liver damage in mice.

PMID- 10934160
TI  - Patterns of chromosomal imbalances in parathyroid carcinomas.
AB  - In this study we have characterized chromosomal imbalances in a panel of 29
      parathyroid carcinomas using comparative genomic hybridization (CGH). The most
      frequently detected imbalances were losses of 1p and 13q that were seen in >40%
      of the cases. The commonly occurring regions of loss were assigned to 1p21-p22
      (41%), 13q14-q31 (41%), 9p21-pter (28%), 6q22-q24 (24%), and 4q24 (21%), whereas
      gains preferentially involved 19p (45%), Xc-q13 (28%), 9q33-qter (24%), 1q31-q32
      (21%) and 16p (21%). The distribution of CGH alterations supports the idea of a
      progression of genetic events in the development of parathyroid carcinoma, where
      gains of Xq and 1q would represent relatively early events that are followed by
      loss of 13q, 9p, and 1p, and by gain of 19p. A sex-dependent distribution was
      also evident for two of the common alterations with preferential gain of 1q in
      female cases and of Xq in male cases. When the CGH profiles for the 29 carcinomas
      were compared with our previously published results for sporadic parathyroid
      adenomas, highly significant differences were revealed. Loss of 1p, 4q, and 13q
      as well as gains of 1q, 9q, 16p, 19p and Xq were significantly more common in the
      carcinomas than in the adenomas. In contrast, loss of the 11q13 region, which is
      the most common CGH abnormality in sporadic adenomas, was not detected in any of
      the carcinomas. Taken together, the findings identify several candidate locations
      for tumor suppressor genes and oncogenes that are potentially involved in
      parathyroid carcinogenesis.

PMID- 10934161
TI  - Induction of MDM2-P2 transcripts correlates with stabilized wild-type p53 in
      betel- and tobacco-related human oral cancer.
AB  - MDM2, a critical element of cellular homeostasis mechanisms, is involved in
      complex interactions with important cell-cycle and stress-response regulators
      including p53. The mdm2-P2 promoter is a transcriptional target of p53. The aim
      of this study was to determine the association between mdm2-P2 transcripts and
      the status of the p53 gene in betel- and tobacco-related oral squamous cell
      carcinomas (SCCs) to understand the mechanism of deregulation of MDM2 and p53
      expression and their prognostic implications in oral tumorigenesis. Elevated
      levels of MDM2 proteins were observed in 11 of 25 (44%) oral hyperplastic
      lesions, nine of 15 (60%) dysplastic lesions, and 71 of 100 (71%) SCCs. The
      intriguing feature of the study was the identification and different subcellular
      localization of three isoforms of MDM2 (ie, 90 kd, 76 kd, and 57 kd) in oral SCCs
      and their correlation with p53 overexpression in each tumor. The hallmark of the
      study was the detection of mdm2-P2 transcripts in 12 of 20 oral SCCs
      overexpressing both MDM2 and p53 proteins while harboring wild-type p53 alleles.
      Furthermore, mdm2 amplification was an infrequent event in betel- and tobacco
      associated oral tumorigenesis. The differential compartmentalization of the three
      isoforms of MDM2 suggests that each has a distinct function, potentially in the
      regulation of p53 and other gene products implicated in oral tumorigenesis. In
      conclusion, we report herein the first evidence suggesting that enhanced
      translation of mdm2-P2 transcripts (S-mdm2) may represent an important mechanism
      of overexpression and consequent stabilization and functional inactivation of
      wild-type p53 serving as an adverse prognosticator in betel- and tobacco-related
      oral cancer. The clinical significance of the functional inactivation of wild
      type p53 by MDM2 is underscored by the significantly shorter median disease-free
      survival time (16 months) observed in p53/MDM2-positive cases as compared to
      those which did not show co-expression of these proteins (median time, 26 months;
      P = 0.02).

PMID- 10934162
TI  - Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury
      in mice by a caspase inhibitor.
AB  - LPS (lipopolysaccharide) is one of the major factors that induce acute lung
      injury. Recently, it was reported that LPS induced disseminated endothelial
      apoptosis, preceding nonendothelial tissue damage. Caspases play important roles
      in apoptosis, including tumor necrosis factor-alpha-induced apoptosis, in several
      systems. We therefore investigated whether the injection of a caspase inhibitor
      prevents LPS-induced apoptosis and acute lung injury in mice. LPS (30 mg/kg) was
      administered intravenously to Institute for Cancer Research mice. Electron
      microscopic findings demonstrated characteristic features of apoptosis in
      endothelial cells and alveolar epithelial cells. The caspase-3 activity and the
      number of terminal dUTP nick-end labeling-positive cells in lung tissues were
      significantly increased after LPS administration. Benzyloxycarbonil-Val-Ala-Asp
      fluoromethylketone (Z-VAD.fmk), which is a broad-spectrum caspase inhibitor, was
      injected before and after the administration of LPS. The injection of Z-VAD.fmk
      suppressed the caspase-3 activity in lung tissues, and significantly decreased
      the number of terminal dUTP nick-end labeling-positive cells. Furthermore, the
      survival rate of mice was prolonged significantly by the injection of Z-VAD.fmk.
      These results indicate that apoptosis may play an important role in acute lung
      injury, and thus that inhibition of caspase activity may constitute a new
      therapeutic approach for treatment of this disease.

PMID- 10934164
TI  - Effect of the E200K mutation on prion protein metabolism. Comparative study of a
      cell model and human brain.
AB  - The hallmark of prion diseases is the cerebral accumulation of a conformationally
      altered isoform (PrP(Sc)) of a normal cellular protein, the prion protein
      (PrP(C)). In the inherited form, mutations in the prion protein gene are thought
      to cause the disease by altering the metabolism of the mutant PrP (PrP(M))
      engendering its conversion into PrP(Sc). We used a cell model to study
      biosynthesis and processing of PrP(M) carrying the glutamic acid to lysine
      substitution at residue 200 (E200K), which is linked to the most common inherited
      human prion disease. PrP(M) contained an aberrant glycan at residue 197 and
      generated an increased quantity of truncated fragments. In addition, PrP(M)
      showed impaired transport of the unglycosylated isoform to the cell surface.
      Similar changes were found in the PrP isolated from brains of patients affected
      by the E200K variant of Creutzfeldt-Jakob disease. Although the cellular PrP(M)
      displayed some characteristics of PrP(Sc), the PrP(Sc) found in the E200K brains
      was quantitatively and qualitatively different. We propose that the E200K
      mutation cause the same metabolic changes of PrP(M) in the cell model and in the
      brain. However, in the brain, PrP(M) undergoes additional modifications, by an
      age-dependent mechanism that leads to the formation of PrP(Sc) and the
      development of the disease.

PMID- 10934163
TI  - Expression of angiotensin AT(1) and AT(2) receptors in adult rat cardiomyocytes
      after myocardial infarction. A single-cell reverse transcriptase-polymerase chain
      reaction study.
AB  - The effector hormone of the renin-angiotensin system, angiotensin II, plays a
      major role in cardiovascular regulation. In rats, both angiotensin receptor
      subtypes, AT(1) and AT(2), are up-regulated after myocardial infarction but
      previous studies failed to identify the cell types which express the AT(2)
      receptor in the heart. To address this question we established a single-cell
      reverse transcriptase-polymerase chain reaction for AT(1) and AT(2) receptors to
      determine whether these receptor subtypes are expressed in adult rat
      cardiomyocytes before and 1 day after myocardial infarction. By laser-assisted
      cell picking, section profiles of single cells without genomic DNA contamination
      were isolated. After dividing samples into two identical aliquots, polymerase
      chain reaction amplification for AT(1) and AT(2) receptors was carried out and
      polymerase chain reaction products were subjected to gel electrophoresis.
      Compared to control (n = 4) and sham-operated animals (n = 4), the number of
      cardiomyocytes expressing the AT(1) receptor mRNA 1 day after myocardial
      infarction (n = 4) was not changed (42% and 33% versus 45%, respectively). On the
      other hand, AT(2) receptor mRNA was expressed in 8% and 13%, respectively, of
      cardiomyocytes gained from control (n = 4) and sham-operated animals (n = 4) and
      in 14% isolated after myocardial infarction (n = 4). These results demonstrate
      for the first time that the AT(2) receptor is expressed in adult cardiomyocytes
      in vivo. They further suggest that the previously observed up-regulation of
      cardiac AT(1) and AT(2) receptors after myocardial infarction involves cell types
      other than cardiomyocytes.

PMID- 10934165
TI  - Staging of cytoskeletal and beta-amyloid changes in human isocortex reveals
      biphasic synaptic protein response during progression of Alzheimer's disease.
AB  - We have examined the relationships between dementia, loss of synaptic proteins,
      changes in the cytoskeleton, and deposition of beta-amyloid plaques in the
      neocortex in a clinicopathologically staged epidemiological cohort using a
      combination of biochemical and morphometric techniques. We report that loss of
      synaptic proteins is a late-stage phenomenon, occurring only at Braak stages 5
      and 6, or at moderate to severe clinical grades of dementia. Loss of synaptic
      proteins was seen only after the emergence of the full spectrum of tau and beta
      amyloid pathology in the neocortex at stage 4, but not in the presence of beta
      amyloid plaques alone. Contrary to previous studies, we report increases in the
      levels of synaptophysin, syntaxin, and SNAP-25 at stage 3 and of alpha-synuclein
      and MAP2 at stage 4. Minimal and mild clinical grades of dementia were associated
      with either unchanged or elevated levels of synaptic proteins in the neocortex.
      Progressive aggregation of paired helical filament (PHF)-tau protein could be
      detected biochemically from stage 2 onwards, and this was earliest change
      relative to the normal aging background defined by Braak stage 1 that we were
      able to detect in the neocortex. These results are consistent with the
      possibility that failure of axonal transport associated with early aggregation of
      tau protein elicits a transient adaptive synaptic response to partial de
      afferentation that may be mediated by trophic factors. This early abnormality in
      cytoskeletal function may contribute directly to the earliest clinically
      detectable stages of dementia.

PMID- 10934166
TI  - Identification of genetic loci controlling the characteristics and severity of
      brain and spinal cord lesions in experimental allergic encephalomyelitis.
AB  - Experimental allergic encephalomyelitis (EAE) is the principal genetically
      determined animal model for multiple sclerosis (MS), the major inflammatory
      disease of the central nervous system (CNS). Although genetics clearly play a
      role in susceptibility to MS, attempts to identify the underlying genes have been
      disappointing. Considerable variation exists between MS patients with regard to
      the severity of clinical signs, mechanism of demyelination, and location of CNS
      lesions, confounding the interpretation of genetic data. A mouse-human synteny
      mapping approach may allow the identification of candidate susceptibility loci
      for MS based on the location of EAE susceptibility loci. To date, 16 regions of
      the mouse genome have been identified that control susceptibility or clinical
      signs of EAE. In this work, we examined the genetic control of histopathological
      lesions of EAE in an F2 intercross population generated from the EAE susceptible
      SJL/J and EAE resistant B10.S/DvTe mouse strains. Composite interval mapping was
      used to identify 10 quantitative trait loci (QTL), including seven newly
      identified loci controlling the distribution and severity of CNS lesions
      associated with murine EAE. QTL on chromosome 10 control lesions in the brain,
      whereas QTL on chromosomes 3, 7, and 12 control lesions in the spinal cord.
      Furthermore, sexually dimorphic QTL on chromosomes 2, 9, and 11 control CNS
      lesions in females, whereas QTL on chromosomes 10, 11, 12, 16, and 19 control
      lesions in males. Our results suggest that the severity and location of CNS
      lesions in EAE are genetically controlled, and that the genetic component
      controlling the character and severity of the lesions can be influenced by sex.

PMID- 10934167
TI  - Proinflammatory cytokine, chemokine, and cellular adhesion molecule expression
      during the acute phase of experimental brain abscess development.
AB  - Brain abscess represents the infectious disease sequelae associated with the
      influx of inflammatory cells and activation of resident parenchymal cells in the
      central nervous system. However, the immune response leading to the establishment
      of a brain abscess remains poorly defined. In this study, we have characterized
      cytokine and chemokine expression in an experimental brain abscess model in the
      rat during the acute stage of abscess development. RNase protection assay
      revealed the induction of the proinflammatory cytokines interleukin (IL)-1alpha,
      IL-1beta, IL-6, and tumor necrosis factor-alpha as early as 1 to 6 hours after
      Staphylococcus aureus exposure. Evaluation of chemokine expression by reverse
      transcription-polymerase chain reaction demonstrated enhanced levels of the CXC
      chemokine KC 24 hours after bacterial exposure, which correlated with the
      appearance of neutrophils in the abscess. In addition, two CC chemokines,
      monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha
      were induced within 24 hours after S. aureus exposure and preceded the influx of
      macrophages and lymphocytes into the brain. Analysis of abscess lesions by in
      situ hybridization identified CD11b+ cells as the source of IL-1beta in response
      to S. aureus. Both intercellular adhesion molecule-1 and platelet endothelial
      cell adhesion molecule expression were enhanced on microvessels in S. aureus but
      not sterile bead-implanted tissues at 24 and 48 hours after treatment. These
      results characterize proinflammatory cytokine and chemokine expression during the
      early response to S. aureus in the brain and provide the foundation to assess the
      functional significance of these mediators in brain abscess pathogenesis.

PMID- 10934168
TI  - Rapid development of vein graft atheroma in ApoE-deficient mice.
AB  - Several animal models manifesting lesions resembling neointimal hyperplasia of
      human vein grafts have been developed, but no spontaneous atheromatous lesions in
      their vein grafts have been observed. We developed and here characterize a new
      animal model of vein graft atheroma, a maturated atherosclerotic plaque, in apoE
      deficient mice. The lesion displayed classical complex morphological features and
      heterogeneous cellular compositions and consisted of a fibrous cap, infiltrated
      mononuclear cells, foam cells, cholesterol crystal structure, necrotic core with
      calcification, and neovasculature. Cell component analysis revealed smooth muscle
      cells (SMCs) localized in the cap region, macrophages which made up a large
      portion of the lesions, and CD4+ T cells scattered under the cap. Importantly,
      apoptotic/necrotic cells determined by TUNEL assay in vein grafts into apoE-/-
      mice were significantly higher than wild-type mice, although a similar number of
      proliferating cell nuclear antigen-positive cells in both types of lesions was
      found. Interestingly, vascular SMCs cultivated from aortas of apoE-deficient mice
      showed a high rate of spontaneous apoptosis/necrosis and a higher rate of cell
      death stimulated by a nitric oxide donor, sodium nitroprusside, H(2)O(2), and
      oxidized low density lipoprotein (LDL), although no difference in proliferation
      of both SMCs incubated with platelet-derived growth factor, angiotensin II, LDL,
      and oxidized LDL was seen. Thus, the pathogenic mechanisms of vein graft atheroma
      involve increased intimal cell death initiated by biomechanical stress and
      amplified by hypercholesterolemia, which leads to continuous recruitment of blood
      mononuclear cells to constitute atheromatous lesions. This mouse model resembling
      human vein graft disease has many advantages over other animal models.

PMID- 10934169
TI  - Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid
      carcinomas.
AB  - Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene
      and, following loss of p53 function, may progress to anaplastic carcinomas. Mice
      with thyroid-targeted expression of ret/PTC1 developed papillary thyroid
      carcinomas that were minimally invasive and did not metastasize. These mice were
      crossed with p53-/- mice to investigate whether loss of p53 would promote
      anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53
      /- mice died or were euthanized by 17 weeks of age due to the development of
      thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1
      mice developed thyroid carcinomas, but tumors in p53-/- mice were more
      anaplastic, larger in diameter, more invasive, and had a higher mitotic index
      than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any
      of the experimental p53+/+ and p53+/- mice </=28 weeks of age or p53-/- mice </=
      17 weeks of age; however, an older (170-day-old) male p53-/- mouse used to
      maintain the colony developed anaplastic thyroid carcinoma with liver metastases.
      These findings demonstrate that the lack of functional p53 in ret/PTC1 mice
      promotes anaplasia and invasiveness of thyroid carcinomas.

PMID- 10934171
TI  - Online access to CGH data of DNA sequence copy number changes.

PMID- 10934170
TI  - TRAF4 deficiency leads to tracheal malformation with resulting alterations in air
      flow to the lungs.
AB  - TRAF4 is one of six identified members of the family of TNFR-associated factors.
      While the other family members have been found to play important roles in the
      development and maintenance of a normal immune system, the importance of TRAF4
      has remained unclear. To address this issue, we have generated TRAF4-deficient
      mice. Despite widespread expression of TRAF4 in the developing embryo, as well as
      in the adult, lack of TRAF4 expression results in a localized, developmental
      defect of the upper respiratory tract. TRAF4-deficient mice are born with a
      constricted upper trachea at the site of the tracheal junction with the larynx.
      This narrowing of the proximal end of the trachea results in respiratory air flow
      abnormalities and increases rates of pulmonary inflammation. These data
      demonstrate that TRAF4 is required to regulate the anastomosis of the upper and
      lower respiratory systems during development.

PMID- 10934172
TI  - Academic general practice: no time for ivory towers.

PMID- 10934173
TI  - 'Partners in pain'--the game of painmanship revisited.

PMID- 10934174
TI  - Primary care involvement in human immune deficiency virus infection-a pan
      European view. The Eurosupport Study Group.
AB  - OBJECTIVE: The aim of this study was to compare the primary care experiences of
      human immunodeficiency virus (HIV)-positive individuals across Europe. METHODS:
      An anonymous self-administered questionnaire study was carried out between August
      1996 and August 1997. A total of 15 HIV/AIDS treatment centres and 14 HIV support
      organizations in 11 European countries participated in the distribution of
      questionnaires. Overall, 1366 completed questionnaires were included in the
      analysis from a total of 2751 distributed (50% response rate). The majority of
      respondents were homosexual men (53.6%), and 54.2% had AIDS or symptomatic HIV
      disease. The main outcome measures were use of GP services in the preceding 6
      months, GP involvement in HIV care provision, satisfaction with current service
      provision and reasons for non-involvement of the primary care services. RESULTS:
      Most patients (64.8%) had visited their GP at least once in the preceding 6
      months, but 53.9% of respondents reported that their GP was not involved in their
      HIV care. Of these patients, 53.4% would like their GP to be involved. Patients
      from central European countries were more likely to have seen their GP than their
      counterparts from northern and southern countries (P < 0.005), and were less
      worried that the GP would not have enough knowledge about HIV (P = 0.002) or
      would not be sympathetic (P = 0.052). CONCLUSIONS: There are clear differences in
      GP utilization by HIV-positive individuals across Europe, reflecting in part
      local service provision but primarily patients' attitudes and beliefs. Strategies
      to promote the involvement of primary health care services need to address
      patients' core beliefs, if these are to be changed.

PMID- 10934175
TI  - Attitudes to lifestyle risk factors for coronary heart disease amongst South
      Asians in Leicester: a focus group study.
AB  - BACKGROUND: South Asians have a significantly higher risk of mortality from
      coronary heart disease (CHD) compared with the general population in the UK.
      There is a lack of evidence on attitudes to and knowledge of risk factors for CHD
      amongst South Asians. Such information is important for the provision of
      effective health promotion services. OBJECTIVES: The aim of the study was to
      identify key issues relating to knowledge of and attitudes to lifestyle risk
      factors for CHD amongst South Asians aged over 40 years in Leicester, UK. METHOD:
      A qualitative focus group analysis was carried out using randomly selected South
      Asians from GP lists and South Asians attending community centres. Group
      discussions were taped, translated and transcribed. The transcripts were analysed
      using qualitative methodology to identify key issues and themes. RESULTS:
      Participants expressed a range of attitudes to and different levels of knowledge
      of lifestyle risk factors for CHD. Barriers to improving lifestyle with respect
      to diet and exercise were identified; these included lack of information (e.g. of
      how to cook traditional Indian food more healthily) and cultural barriers, such
      as lack of women-only exercise facilities. Participants perceived stress as an
      important cause of CHD, and stress directly related to ethnic minority status was
      described frequently. Language was identified as a key barrier to accessing
      health services. CONCLUSION: Health professionals need to provide individually
      tailored health promotion for South Asians which avoids stereotyping, but
      recognizes potential cultural obstacles to change. The issue of stress amongst
      South Asians requires more research and needs to be recognized as an important
      issue by health professionals. South Asians still face problems accessing health
      and leisure services due to language and cultural issues.

PMID- 10934176
TI  - Socio-economic characteristics of adult frequent attenders in general practice:
      secondary analysis of data.
AB  - OBJECTIVE: This study was carried out to determine the effect of a range of socio
      economic features on frequent attendance in general practice from a large
      database of general practice consultations using two definitions of frequent
      attendance. METHODS: Secondary analyses were carried out of data from the Fourth
      National Survey of Morbidity in General Practice covering 60 general practices in
      England and Wales. A total of 283 842 adult patients and their consultations
      between September 1991 and August 1992 were examined. The main outcome measure
      was the odds ratio of being a frequent attender (95% confidence intervals).
      RESULTS: Using a definition of 12+ consultations/year, men were less likely to be
      frequent attenders (OR 0.14, 95% CI 0.13-0.17); however, the difference between
      men and women lessens with age. Patients who were more likely to be frequent
      attenders included those who were divorced or widowed (1.41, 1.31-1.51); from
      social classes IIIM (1.23, 1.17-1.29) and IV/V (1.33, 1.26-1.41); South Asian
      people (1.38, 1.16-1.65); or unemployed (1.61, 1.46-1.77). Other factors
      signifying isolation or poverty were also linked to frequent attendance. Using
      the definition of '6+ consultations for minor problems' produced broadly similar
      results although the relative weight of the factors showed some differences.
      CONCLUSIONS: Socio-economic factors were important indicators of frequent
      attendance in general practice. Results were very similar using either
      definition, suggesting that both are valid for further work. Furthermore,
      frequent attendance is a complex process associated with many factors outside the
      control of the GP.

PMID- 10934177
TI  - Health services can be cool: partnership with adolescents in primary care.
AB  - Young people's health is giving rise to increasing concern. However, despite
      recent government emphasis on patient involvement and partnership, little
      discussion has occurred concerning how this may be achieved with younger age
      groups in primary care. Here we outline issues relating to adolescents' health
      and characteristics of current provision. These are considered in the context of
      innovative services that have incorporated adolescents' views. Finally, we
      discuss the challenge of establishing a partnership with adolescents and propose
      strategies for achieving this.

PMID- 10934178
TI  - Family physician job satisfaction in different medical care organization models.
AB  - OBJECTIVES: The aim of the present study was to estimate physician job
      satisfaction at the Mexican Institute of Social Security (IMSS), the Ministry of
      Health (SSA) and in the private sector, and to measure the association between
      these different family medical care organization models. METHODS: A comparative
      cross-sectional design was used to investigate the job satisfaction of family
      physicians in private and institutional family medicine clinics. Satisfaction was
      measured with a previously constructed and validated instrument. The instrument
      measures the satisfaction in four areas: 'global satisfaction', 'institution
      where the physician works', 'the patients' and 'themselves as physicians'.
      RESULTS: One hundred and seven IMSS physicians, 106 SSA physicians and 97 private
      physicians were selected randomly from a census according to the sample size. The
      sample was weighted. Fifty-one percent of IMSS and SSA physicians were
      dissatisfied, against 25% in the private sector, in the first three areas.
      Comparing the private model and the IMSS, differences were found (P < 0.0001) in
      the area of 'global satisfaction' [odds ratio (OR) = 2.47, 95% confidence
      interval (CI) 1.69-3.67], 'institution where the physician works' (OR = 2.12, CI
      1. 45-3.13) and 'themselves as physicians' (OR = 1.84, CI 1.28-2.65). When the
      private/SSA groups were compared, the differences were similar (P < 0.0001). No
      differences were found in terms of 'the patients'. When stratifying, the risks
      increased in females, in the group aged 31-40 years and in specialists in family
      medicine. CONCLUSIONS: The organization model is associated with dissatisfaction
      in all areas, except in 'the patients'.

PMID- 10934179
TI  - Lung function measurement in general practice. General practice measurements
      compared with laboratory measurements during the DIMCA trial.
AB  - BACKGROUND: Lung function measurement in the general practice setting (GPS) is of
      growing importance. OBJECTIVE.:The aim of this study was to compare results from
      a lung function laboratory (LFL) with those in a GPS. METHODS: Comparisons were
      made for decline calculated from GPS and LFL measurements and intra-individual
      paired measurements. Test characteristics of the spirometer used in the GPS were
      also assessed. RESULTS: The mean decline in lung function was: -0.037 l/year [95%
      confidence interval (CI) -0.202 to 0.129] from LFL data and -0.027 l/year (95% CI
      -0.242 to 0.188) from GPS data. The mean intra-individual difference was -0.0025
      l (95% CI -0.493 to 0.488 l). The test characteristics of the spirometer used in
      GPS did not meet all of the American Thoracic Society guidelines; in particular,
      the random error was too large. The difference in assessments between measurement
      in LFL and GPS were such that misclassification might occur if slopes were
      calculated. CONCLUSIONS. :Repeated measurement in this study showed that GPS
      measurements are not interchangeable with LFL measurements. Therefore, one has to
      be cautious when interchanging lung function data from an LFL and a GPS.

PMID- 10934180
TI  - Tympanometry for diagnosis and treatment of otitis media in general practice.
AB  - OBJECTIVE: The aim of this study was to evaluate the role of tympanometry for
      diagnosis, treatment and follow-up of otitis media in general practice. METHODS:
      The results from otoscopy performed by 40 physicians in general practice in Vejle
      County, Denmark were combined with the clinical condition and this was recorded
      as the preliminary decision about diagnosis, treatment and follow-up.
      Subsequently, tympanometry was performed in 3176 children aged between 1 month
      and 16 years; a total of 6352 tympanometries. With this added knowledge, a final
      decision about diagnosis, treatment and follow-up was recorded. The practitioners
      were trained in performing tympanometry including the interpretation of the
      results. Simultaneously, they were involved in the establishment of guidelines
      for diagnosis, treatment and follow-up of otitis media in general practice. The
      main outcome measures were changes between preliminary and final decisions about
      diagnoses, treatments and follow-up regimens. RESULTS: Tympanometry was performed
      successfully in 87.7% of the children, and in 26.4% changes in diagnoses were
      found. However, tympanometry did not influence the distributions of the main
      outcome measures in the sample as a whole. Uncomplicated cases were checked in
      general practice and referrals to specialists were not increased. CONCLUSION:
      Tympanometry can be performed successfully in general practice after appropriate
      instruction. In 26.4% of children, the diagnoses were changed, which may result
      in more appropriate treatment and follow-up. Tympanometry is a clinically
      relevant supplement to the examination of a child in general practice.

PMID- 10934181
TI  - The general practice perspective on cancer services in Lothian.
AB  - OBJECTIVES: The aim of the present study was to obtain views from general
      practices about current and potential improvements to services for patients with
      suspected lung, large bowel, non-melanoma skin and breast cancer. METHOD: A
      questionnaire study was carried out of 134 general practices within the Lothian
      Health Board boundary. Information was sought about referral choices,
      communication, quality of care, liaison between community and hospital, health
      promotion, treatment outcomes and palliative care. Main outcome measures were
      determinants of primary care referral behaviour and clinical investigation
      strategies, and perception of quality in secondary care and health promotion
      services. RESULTS: Seventy-nine general practices (59%) returned completed
      questionnaires. One-fifth of practices maintained a cancer register, and 85%
      provide patient information about cancer prevention. Initial management was
      disease dependent. Most cases of suspected lung cancer, about half of suspected
      colorectal cancer cases and very few cases of suspected breast cancer were
      investigated in primary care before referral to hospital. Hospital referral
      depended on knowledge of local services. A minority of practices wanted referral
      guidelines. It was estimated that 92% of lung and breast cancer cases, 68% of
      colorectal cancers and 35% of skin cancers are seen within 4 weeks. Breast cancer
      care was rated more highly than that for other cancers. One-third ranked
      community nursing support as 'excellent' and 10-15% described it as 'fair' or
      'poor'; 77% describe palliative care as 'excellent' or 'good'. Fifty-one percent
      believe that communication with hospital is 'excellent' or 'good'. Practices were
      sometimes unaware of the hospital's post-diagnosis management plan; communication
      was often too slow and practices often received 'poor' advice about symptom
      control. Eighty percent thought that hospital follow-up for breast, colorectal
      and lung cancer should be routine; 20% thought that it was indicated for non
      melanomatous skin cancer. CONCLUSIONS: Communication problems between primary and
      secondary sectors need to be tackled innovatively and the perceived quality
      variation in services addressed-perhaps by developing local guidelines. Practices
      would welcome further education about health promotion resources and cancer
      epidemiology.

PMID- 10934182
TI  - Effects of screening for disorders among the elderly: an intervention study in
      general practice.
AB  - BACKGROUND: Preventive assessment of prevalent disorders may be considered as an
      instrument to maintain independence in the elderly. However, the outcomes of
      studies on these types of screening differ considerably regarding their effects.
      OBJECTIVES: The aim of the present study was to assess the effects of GPs'
      screening of the elderly on four highly prevalent disorders with possibilities
      for treatment: hearing and visual disorders, urinary incontinence and mobility
      disorders. METHODS: In an intervention study in 12 general practices, 1121
      subjects aged 75 years and over were screened. Randomization was done by practice
      into an intervention group (576) and a control group (545). In the intervention
      group, all elderly patients were screened for the four disorders during the first
      year of the study. When the GP and patient agreed on intervention, usual care was
      provided by the GP. The patients in the control group were not screened in the
      first year. In the second year, all patients in both groups were screened for the
      four disorders. RESULTS: For none of the four disorders was a measurable effect
      of the screening at the population level found. In the first year, 1013 new
      disorders were found involving 479 of 576 people. The GPs considered information
      to be new in 293 cases. In 245 cases (out of 293), the GP discussed the new
      information with the patient. Of the 89 cases in which the patient agreed with an
      intervention, improvement was reported in 17 cases. CONCLUSIONS: Implementing a
      standardized screening programme for four highly prevalent disorders for elderly
      people is not recommended. Preventive assessment of the elderly should be applied
      in ways other than by screening. Preventive care should pay attention to the
      individual needs of the elderly, should be started before the age of 75 years and
      should be offered in a flexible way.

PMID- 10934183
TI  - Japanese paediatricians' judgement of the appropriateness of bathing for children
      with colds.
AB  - OBJECTIVES: This study investigated the decisions which Japanese paediatricians
      make regarding bathing a child with a common cold. METHODS: A total of 486
      printed questionnaires were mailed to paediatricians systematically sampled from
      the list of members of the Japanese Pediatric Association. The questionnaire
      included two main questions. (i) Do you permit a 2- to 4-year-old child with a
      common cold to take a bath? (ii) If the answer to (i) was 'yes', what conditions
      should limit bathing of such children, and if the answer was 'no', why do you
      forbid bathing? In addition, the questionnaire included the age and sex of the
      practitioner, and the type and location of the practice. RESULTS: A total of 269
      paediatricians returned questionnaires (response rate 55%); of these, 88%
      permitted a child with a cold to take a bath. Of these paediatricians, 5%
      permitted it without any conditions. The main conditions for taking a bath
      indicated by these paediatricians were 'no fever' (72%), 'not in a severe
      physical condition' (27%) and 'after 2 or 3 days from onset' (19%). Thirty-nine
      paediatricians indicated a specific body temperature at which bathing was
      appropriate. One-third of these paediatricians did not permit bathing at body
      temperatures above 38 degrees C. Of the 31 paediatricians (12%) who answered that
      a child with a cold should not take a bath, 61% were concerned for the physical
      well-being of the child. However, 29% provided no supporting evidence.
      CONCLUSIONS: Japanese paediatricians' judgements concerning bathing of a child
      with a cold are related to the effects of bathing on physical condition. Bathing
      immersed up to the neck does not always affect physical conditions. It is
      necessary to establish appropriate parental and patient education concerning
      bathing of children with colds.

PMID- 10934184
TI  - Detected atrial fibrillation in north Italy: rates, calculated stroke risk and
      proportion of patients receiving thrombo-prophylaxis.
AB  - BACKGROUND: Atrial fibrillation (AF) is a major risk factor in the development of
      ischaemic stroke. The rate of embolic events can be reduced significantly by
      appropriate therapy. Epidemiological data and information about the attitude of
      physicians towards prophylaxis of thromboembolism are crucial to determine future
      strategies to decrease strokes in patients with AF. Unfortunately, these data are
      unknown in Italy. OBJECTIVES: The aims of this study were to study the prevalence
      of diagnosed AF in northern Italy, to estimate the percentage of high, moderate
      and low risk patients and to investigate the pattern of embolic prophylaxis among
      GPs. METHODS: Fifty-one GPs reviewed all the clinical records of subjects aged
      >/=40 years and identified those patients with chronic or paroxysmal AF. RESULTS:
      Among 41 050 patients, 719 [1.75%; 95% confidence interval (CI) 1.59-1.91] had AF
      (70% chronic, 30% paroxysmal). Only 4% were at low risk for ischaemic stroke,
      whereas 32% were at moderate and 64% at high risk. Contraindications to
      antiplatelet or anticoagulant therapy were present in 11% of AF patients.
      Antithrombotic prophylaxis was underused among the 51 GPs. CONCLUSIONS: Detection
      of AF could be 30-40% lower than real prevalence and, therefore, adequate
      evaluation and treatment aimed at avoiding ischaemic stroke could be denied to a
      great number of Italian patients. AF detection and prophylaxis of thromboembolic
      risk can be improved among GPs in northern Italy.

PMID- 10934185
TI  - The demand for out-of-hours care from GPs: a review.
AB  - BACKGROUND: The perception of a relentless increase in demand for out-of-hours
      care has led to the development of new models of organization. A comprehensive
      review of the evidence about the demand for out-of-hours care has, however, been
      lacking. OBJECTIVE: The aim of this study was to review all published work
      relating to out-of-hours care in UK general practice which included data about
      the demand for care, and the variation in demand. METHODS: Searches were
      conducted in MEDLINE (1966-December 1999) and EMBASE (1988- October 1999).
      Further references were identified from those cited in papers, and by use of the
      Science Citation Index to extract articles which cited key papers. Information
      about night visit fee claims was also obtained from the NHS performance
      indicators. The review was restricted to research in the UK published since 1959.
      RESULTS AND CONCLUSIONS: The activity of GPs has been used as a proxy indicator
      for the demand for out-of-hours primary care. Most research has been based on
      claims for night visit fees, which reflect only a small proportion of all out-of
      hours care. Night visit rates vary widely between areas, practices and individual
      doctors, for reasons which remain largely unexplained. There is evidence that
      levels of provision of out-of-hours care have risen considerably, but the wide
      variation between areas, and differences between studies in terms of definition
      and methodology, make it difficult to confirm this finding. The recent use of
      electronic call management systems by general practice co-operatives allows an
      accurate assessment to be made from routinely collected data of the total demand
      for out-of-hours care. This information will make it possible to assess the
      impact on general practice of new models of service provision, such as NHS Direct
      and primary care walk-in centres.

PMID- 10934186
TI  - What is the ideal body weight?

PMID- 10934187
TI  - Chronic pain in primary care.

PMID- 10934188
TI  - dFADD, a novel death domain-containing adapter protein for the Drosophila caspase
      DREDD.
AB  - Apoptotic cell death occurs through activation of procaspases, the precursors of
      a group of aspartate-specific cysteine proteases known as caspases. Procaspase
      activation is mediated by death adapter proteins such as the mammalian proteins
      FADD and Apaf-1 and the Caenorhabditis elegans protein CED-4. These adapters bind
      to procaspases and facilitate oligomerization and subsequent auto-proteolytic
      processing of the zymogens. Here we report cloning and characterization of dFADD,
      a FADD homologue in Drosophila. dFADD contains a death domain that is highly
      homologous to the FADD death domain, and it also shares a novel domain with a
      Drosophila caspase DREDD, which we call death-inducing domain. dFADD binds to
      DREDD through the death-inducing domain and enhances the cell death activity and
      proteolytic processing of DREDD. dFADD and DREDD are stabilized by their
      interaction. The structural and functional similarities between dFADD and FADD
      suggest the existence of a FADD-like apoptosis pathway in Drosophila.

PMID- 10934189
TI  - Functional interaction between the p160 coactivator proteins and the
      transcriptional enhancer factor family of transcription factors.
AB  - SRC1, initially identified as a nuclear receptor coactivator, was found to
      interact with a member of the transcriptional enhancer factor (TEF) family of
      transcription factors, TEF-4. The interaction, which occurs in both intact cells
      and in a cell-free system, is mediated by the highly conserved basic helix-loop
      helix/Per-Arnt-Sim (bHLH-PAS) domain present in the N-terminal region of SRC1.
      Moreover, all three members of the p160 family of nuclear receptor coactivators,
      SRC1, TIF2, and RAC3, are able to potentiate transcription from a TEF response
      element in transient transfection experiments, and this activation requires the
      presence of the bHLH-PAS domain. These results suggest that the p160 proteins
      could be bona fide coactivators of the TEF family of transcription factors.

PMID- 10934190
TI  - Mechanism of inactivation of NF-kappa B by a viral homologue of I kappa b alpha.
      Signal-induced release of i kappa b alpha results in binding of the viral
      homologue to NF-kappa B.
AB  - Activation of the nuclear factor kappa B plays a key role in viral pathogenesis,
      resulting in inflammation and modulation of the immune response. We have
      previously shown that A238L, an open reading frame from African swine fever virus
      (ASFV), encoding a protein with 40% homology to porcine I kappa B alpha exerts a
      potent anti-inflammatory effect in host macrophages, where it down-regulates NF
      kappa B-dependent gene transcription and proinflammatory cytokine production.
      This paper reveals the mechanism of suppression of NF-kappa B activity by A238Lp.
      A238Lp is synthesized throughout infection as two molecular mass forms of 28 and
      32 kDa, and vaccinia-mediated expression of A238L demonstrated that both proteins
      are produced from a single gene. Significantly, the higher 32-kDa form of A238L,
      but not the 28-kDa form, interacts directly with RelA, the 65-kDa subunit of NF
      kappa B, indicating that the binding is dependent on a post-translational
      modification. Immunoprecipitation analysis shows the NF-kappa B p65-A238L p32
      heterodimer is a separate complex from NF-kappa B-I kappa B alpha, and it resides
      in the cytoplasm. Moreover, we show that ASFV infection stimulates the NF kappa B
      signal transduction pathway, which results in the rapid degradation of endogenous
      I kappa B alpha, although both forms of A238Lp are resistant to stimulus-induced
      degradation. Using the proteasome inhibitor MG132, we show that when degradation
      of I kappa B alpha is inhibited, A238Lp binding to NF-kappa B p65 is reduced. The
      results suggest that the virus exploits its activation of the NF-kappa B pathway
      to enable its own I kappa B homologue to bind to NF-kappa B p65. Last, we show
      that synthesis of I kappa B alpha is increased during ASFV infection, indicating
      RelA-independent transcription of the I kappa B alpha gene.

PMID- 10934191
TI  - Modulation of the catalytic activity of the Src family tyrosine kinase Hck by
      autophosphorylation at a novel site in the unique domain.
AB  - Autophosphorylation is a key event in the activation of protein kinases. In this
      study, we demonstrate that autophosphorylation of the recombinant Src family
      kinase Hck leads to a 20-fold increase in its specific enzymatic activity. Hck
      was found to autophosphorylate readily to a stoichiometry of 1.3 mol of phosphate
      per mol of enzyme, indicating that the kinase autophosphorylated at more than one
      site. Solid phase sequencing and two-dimensional mapping of the phosphopeptide
      fragments derived from the autophosphorylated enzyme revealed that the kinase can
      undergo autophosphorylation at the following two sites: (i) Tyr-388, which is
      located to the consensus autophosphorylation site commonly found in the
      activation loop of many protein kinases, and (ii) Tyr-29, which is located in the
      unique domain of Hck. Hck purified from mouse bone marrow-derived macrophages
      could also autophosphorylate in vitro at both Tyr-388 and Tyr-29, indicating that
      naturally occurring Hck can also autophosphorylate at Tyr-29. Furthermore, Hck
      transiently expressed in human embryonic kidney 293T cells was found to be
      phosphorylated at Tyr-29 and Tyr-388, proving that Hck can also undergo
      autophosphorylation at both sites in vivo. The recombinant enzyme carrying the
      mutation of Tyr-388 to Phe was also able to autophosphorylate at Tyr-29, albeit
      at a significantly slower rate. A 2-fold increase in the specific enzymatic
      activity was seen with this mutant despite the stoichiometry of
      autophosphorylation only approaching 0.2 mol of phosphate per mol of enzyme. This
      indicates that autophosphorylation of Tyr-29 contributes significantly to the
      activation of Hck. Regulation of the catalytic activity by phosphorylation of Tyr
      29 in the unique domain may represent a new mechanism of regulation of Src family
      tyrosine kinases.

PMID- 10934192
TI  - Oxidized low density lipoprotein inhibits interleukin-12 production in
      lipopolysaccharide-activated mouse macrophages via direct interactions between
      peroxisome proliferator-activated receptor-gamma and nuclear factor-kappa B.
AB  - Lipopolysaccharide (LPS) increases the production of interleukin-12 (IL-12) from
      mouse macrophages via a kappaB site within the IL-12 p40 promoter. In this study,
      we found that oxidized low density lipoprotein (oxLDL) inhibited this LPS
      stimulated production of IL-12 in a dose-dependent manner while native LDL did
      not. OxLDL inhibited p40 promoter activation in monocytic RAW264.7 cells
      transiently transfected with p40 promoter/reporter constructs, and the repressive
      effect mapped to a region in the p40 promoter containing a binding site for
      nuclear factor-kappaB (NF-kappaB) (p40-kappaB). Activation of macrophages by LPS
      in the presence of oxLDL resulted in markedly reduced binding to the kappaB site,
      as demonstrated by the electrophoretic mobility shift assays. In contrast, native
      LDL did not inhibit the IL-12 p40 promoter activation and NF-kappaB binding to
      the kappaB sites, suggesting that oxidative modification of LDL was crucial for
      the inhibition of NF-kappaB-mediated IL-12 production. 9-Hydroxyoctadecadienoic
      acid, a major oxidized lipid component of oxLDL, significantly inhibited IL-12
      production in LPS-stimulated mouse macrophages and also suppressed NF-kappaB
      mediated activation in IL-12 p40 promoter. The NF-kappaB components p50 and p65
      directly bound peroxisome proliferator-activated receptor-gamma (PPAR-gamma) in
      vitro. In cotransfections of CV-1 and HeLa cells, PPAR-gamma inhibited the NF
      kappaB transactivation in an oxLDL-dependent manner. From these results, we
      propose that oxLDL-mediated suppression of the IL-12 production from LPS
      activated mouse macrophages may, at least in part, involve both inhibition of the
      NF-kappaB-DNA interactions and physical interactions between NF-kappaB and PPAR
      gamma.

PMID- 10934193
TI  - Structural and functional analysis of the recombinant G domain of the laminin
      alpha4 chain and its proteolytic processing in tissues.
AB  - The C-terminal G domains of laminin alpha chains have been implicated in various
      cellular and other interactions. The G domain of the alpha4 chain was now
      produced in transfected mammalian cells as two tandem arrays of LG modules,
      alpha4LG1-3 and alpha4LG4-5. The recombinant fragments were shown to fold into
      globular structures and could be distinguished by specific antibodies. Both
      fragments were able to bind to heparin, sulfatides, and the microfibrillar
      fibulin-1 and fibulin-2. They were, however, poor substrates for cell adhesion
      and had only a low affinity for the alpha-dystroglycan receptor when compared
      with the G domains of the laminin alpha1 and alpha2 chains. Yet antibodies to
      alpha4LG1-3 but not to alpha4LG4-5 clearly inhibited alpha(6)beta(1) integrin
      mediated cell adhesion to laminin-8, indicating the participation of alpha4LG1-3
      in a cell-adhesive structure of higher complexity. Proteolytic processing within
      a link region between the alpha4LG3 and alpha4LG4 modules was shown to occur
      during recombinant production and in endothelial and Schwann cell culture.
      Cleavage could be attributed to three different peptide bonds and is accompanied
      by the release of the alpha4LG4-5 segment. Immunohistology demonstrated abundant
      staining of alpha4LG1-3 in vessel walls, adipose, and perineural tissue. No
      significant staining was found for alpha4LG4-5, indicating their loss from
      tissues. Immunogold staining demonstrated an association of the alpha4 chain
      primarily with microfibrillar regions rather than with basement membranes, while
      laminin alpha2 chains appear primarily associated with various basement
      membranes.

PMID- 10934195
TI  - Regulation of AP1 (Jun/Fos) factor expression and activation in ovarian granulosa
      cells. Relation of JunD and Fra2 to terminal differentiation.
AB  - AP1 transcription factors control rapid responses of mammalian cells to stimuli
      that impact proliferation, differentiation, and transformation. To determine
      which AP1 factors are present in and regulated by hormones in ovarian cells
      during specific stages of proliferation and differentiation, we used both in
      vitro and in vivo models, Western blotting, immunohistochemistry, DNA binding
      assays, and transfections of AP1 promoter-reporter constructs. The expression
      patterns of Jun and Fos family members in response to hormones (follicle
      stimulating hormone (FSH), luteinizing hormone (LH), and cAMP) were distinct.
      JunB, c-Jun, c-Fos, and Fra2 were rapidly but transiently induced by FSH in
      immature granulosa cells. JunD and Fra2 were induced by LH and maintained as
      granulosa cells terminally differentiated into luteal cells. Forskolin and
      phorbol myristate acetate acted synergistically to enhance transcription of an
      AP1(-73COL)-luciferase construct. JunD appears to be one mediator of this effect,
      since JunD was a major component of the AP1-DNA binding complex in granulosa
      cells, and menin, a selective inhibitor of JunD, blocked transcription of -73COL
      luciferase. Thus, FSH and LH via cAMP induce specific AP1 factors, the AP1
      expression patterns are distinct, and that of JunD and Fra2 correlates with the
      transition of proliferating granulosa cells to terminally differentiated, non
      dividing luteal cells.

PMID- 10934194
TI  - iota-Carrageenases constitute a novel family of glycoside hydrolases, unrelated
      to that of kappa-carrageenases.
AB  - iota-Carrageenases are polysaccharide hydrolases that cleave the beta-1,4
      linkages between the d-galactose-4-sulfate and 3, 6-anhydro-d-galactose-2-sulfate
      residues in the red algal galactans known as iota-carrageenans. We report here on
      the purification of iota-carrageenase activity from the marine bacterium Zobellia
      galactanovorans and on the characterization of iota-carrageenase structural
      genes. Genomic libraries from this latter bacterium as well as from Alteromonas
      fortis were functionally screened for the presence of iota-carrageenase(+)
      clones. The Z. galactanovorans and A. fortis iota-carrageenase genes encode
      homologous proteins of 53.4 and 54.8 kDa, respectively. Based on hydrophobic
      cluster analysis and on the (1)H NMR monitoring of the products of the
      overexpressed A. fortis iota-carrageenase, these enzymes appear to form a new
      family of glycoside hydrolases, unrelated to that of kappa-carrageenases and with
      an inverting mechanism of hydrolysis. They both feature a 45-amino acid-long N
      terminal segment with sequence similarity to the N-terminal region of several
      other polysaccharidases. In those for which a three-dimensional structure is
      available, this conspicuous segment, also deemed "glycanase motif" (Chua, J. E.
      H., Manning, P. A., and Morona, R. (1999) Microbiology (Reading) 145, 1649-1659),
      corresponds to a strand-helix-strand "cap" that covers the N-terminal end of a
      common, right-handed beta-helical fold.

PMID- 10934196
TI  - Modulation of glutathione S-transferase alpha by hepatitis B virus and the
      chemopreventive drug oltipraz.
AB  - Persistent infection by hepatitis B virus (HBV) and exposure to chemical
      carcinogens correlates with the prevalence of hepatocellular carcinoma in endemic
      areas. The precise nature of the interaction between these factors is not known.
      Glutathione S-transferases (GST) are responsible for the cellular metabolism and
      detoxification of a variety of cytotoxic and carcinogenic compounds by catalysis
      of their conjugation with glutathione. Diminished GST activity could enhance
      cellular sensitivity to chemical carcinogens. We have investigated GST isozyme
      expression in hepatocellular HepG2 cells and in an HBV-transfected subline. Total
      GST activity and selenium-independent glutathione peroxidase activity are
      significantly decreased in HBV transfected cells. On immunoblotting, HBV
      transfected cells demonstrate a significant decrease in the level of GST Alpha
      class. Cytotoxicity assays reveal that the HBV transfected cells are more
      sensitive to a wide range of compounds known to be detoxified by GST Alpha
      conjugation. Although no significant difference in protein half-life between the
      two cell lines was found, semi-quantitative reverse transcription-polymerase
      chain reaction shows a reduced amount of GST Alpha mRNA in the transfected cells.
      Because the HBV x protein (HBx) seems to play a role in HBV transfection, we also
      demonstrated that expression of the HBx gene into HepG2 cells decreased the
      amount of GST Alpha protein. Transient transfection experiments using both rat
      and human GST Alpha (rGSTA5 and hGSTA1) promoters in HepG2 cells show a decreased
      CAT activity upon HBx expression, supporting a transcriptional regulation of both
      genes by HBx. This effect is independent of HBx interaction with Sp1. Treatment
      with oltipraz, an inducer of GST Alpha, partially overcomes the effect of HBx on
      both promoters. Promoter deletion studies indicate that oltipraz works through
      responsive elements distinct from AP1 or NF-kappaB transcription factors. Thus,
      HBV infection alters phase II metabolizing enzymes via different mechanisms than
      those modulated by treatment with oltipraz.

PMID- 10934197
TI  - Characterization of the L1-neurocan-binding site. Implications for L1-L1
      homophilic binding.
AB  - The L1 adhesion molecule is a 200-220-kDa membrane glycoprotein of the Ig
      superfamily implicated in important neural processes including neuronal cell
      migration, axon outgrowth, learning, and memory formation. L1 supports homophilic
      L1-L1 binding that involves several Ig domains but can also bind with high
      affinity to the proteoglycan neurocan. It has been reported that neurocan can
      block homophilic binding; however, the mechanism of inhibition and the precise
      binding sites in both molecules have not been determined. By using fusion
      proteins, site-directed mutagenesis, and peptide blocking experiments, we have
      characterized the neurocan-binding site in the first Ig-like domain of human L1.
      Results from molecular modeling suggest that the sequences involved in neurocan
      binding are localized on the surface of the first Ig domain and largely overlap
      with the G-F-C beta-strands proposed to interact with the fourth Ig domain during
      homophilic binding. This suggests that neurocan may sterically hinder a proper
      alignment of L1 domains. We find that the C-terminal portion of neurocan is
      sufficient to mediate binding to the first Ig domain of L1, and we suggest that
      the sushi domain cooperates with a glycosaminoglycan side chain in forming the
      binding site for L1.

PMID- 10934198
TI  - Functional complementation of BLNK by SLP-76 and LAT linker proteins.
AB  - Recent studies have demonstrated a requirement for the SLP-76 (SH2 domain
      containing leukocyte protein of 76 kDa) and LAT (linker for activation of T
      cells) adaptor/linker proteins in T cell antigen receptor activation and T cell
      development as well as the BLNK (B cell linker) linker protein in B cell antigen
      receptor (BCR) signal transduction and B cell development. Whereas the SLP-76 and
      LAT adaptor proteins are expressed in T, natural killer, and myeloid cells and
      platelets, BLNK is preferentially expressed in B cells and monocytes. Although
      BLNK is structurally homologous to SLP-76, BLNK interacts with a variety of
      downstream signaling proteins that interact directly with both SLP-76 and LAT.
      Here, we demonstrate that neither SLP-76 nor LAT alone is sufficient to restore
      the signaling deficits observed in BLNK-deficient B cells. Conversely, the
      coexpression of SLP-76 and LAT together restored BCR-inducible calcium responses
      as well as activation of all three families of mitogen-activated protein kinases.
      Together, these data suggest functional complementation of SLP-76 and LAT in T
      cell antigen receptor function with BLNK in BCR function.

PMID- 10934199
TI  - Kinetic analysis of the cyclin-dependent kinase-activating kinase (Cak1p) from
      budding yeast.
AB  - Cak1p, the Cyclin-dependent kinase-activating kinase from budding yeast, is an
      unusual protein kinase that lacks many of the highly conserved motifs observed
      among members of the protein kinase superfamily. Cak1p phosphorylates and
      activates Cdc28p, the major cyclin-dependent kinase (CDK) in yeast, and is
      thereby required for passage through the yeast cell cycle. In this paper, we
      explore the kinetics of CDK phosphorylation by Cak1p, and we examine the role of
      the catalytic step in the reaction mechanism. Cak1p proceeds by a sequential
      reaction mechanism, binding to both ATP and CDK2 with reasonable affinities,
      exhibiting K(d) values of 7.2 and 0.6 microm, respectively. Interestingly, these
      values are approximately the same as the K(M) values, indicating that the binding
      of substrates is fast with respect to catalysis and that the most likely reaction
      mechanism is rapid equilibrium random. Cak1p is a slow enzyme, with a catalytic
      rate of only 4.3 min(-)(1). The absence of a burst phase indicates that product
      release is not rate-limiting. This result, and a solvent isotope effect, suggests
      that a catalytic step is rate-limiting.

PMID- 10934200
TI  - Side chain orientation in the selectivity filter of a voltage-gated Ca2+ channel.
AB  - Four glutamate residues (EEEE locus) are essential for ion selectivity in voltage
      gated Ca(2+) channels, with ion-specific differences in binding to the locus
      providing the basis of selectivity. Whether side chain carboxylates or
      alternatively main chain carbonyls of these glutamates project into the pore to
      form the ion-binding locus has been uncertain. We have addressed this question by
      examining effects of sulfhydryl-modifying agents (methanethiosulfonates) on 20
      cysteine-substituted mutant forms of an L-type Ca(2+) channel. Sulfhydryl
      modifiers partially blocked whole oocyte Ba(2+) currents carried by wild type
      channels, but this block was largely reversed with washout. In contrast, each of
      the four EEEE locus glutamate --> cysteine mutants (0 position) was persistently
      blocked by sulfhydryl modifiers, indicating covalent attachment of a modifying
      group to the side chain of the substituted cysteine. Cysteine substitutions at
      positions immediately adjacent to the EEEE locus glutamates (+/-1 positions) were
      also generally susceptible to sulfhydryl modification. Sulfhydryl modifiers had
      lesser effects on channels substituted one position further from the EEEE locus
      (+/-2 positions). These results indicate that the carboxylate-bearing side chains
      of the EEEE locus glutamates and their immediate neighbors project into the water
      filled lumen of the pore to form an ion-binding locus. Thus the structure of the
      Ca(2+) channel selectivity filter differs substantially from that of ancestral
      K(+) channels.

PMID- 10934201
TI  - RNA polymerase-cNMP-ligated cAMP receptor protein (CRP) mutant interactions in
      the enhancement of transcription by CRP mutants.
AB  - The enhancement of the transcription of three synthetic promoters by cNMP-ligated
      cAMP receptor protein (CRP)/mutant complexes was determined from the
      transcription yields of a short AAUU transcript in an abortive initiation in
      vitro transcription assay. The cNMP-ligated CRP and mutants were cAMP, cGMP, and
      cIMP ligated with CRP, T127L CRP, S128A CRP, and T127L/S128A CRP. The
      transcriptional activation of a 152-base pair lacUV5 promoter (synlac promoter)
      with a CRP consensus binding site sequence (syncon promoter) was enhanced by an
      average factor of 12.3 +/- 0.5 with the cAMP-ligated complexes of CRP/mutants and
      cGMP-ligated T127L, although their promoter binding site affinities varied by a
      factor of 5. However, in the presence of bound RNA polymerase, the binding
      affinities only ranged from 0.8 +/- 0.2 x 10(7) m(-)(1) for cAMP-ligated CRP* to
      1.8 +/- 0. 3 x 10(7) m(-)(1) for cAMP-ligated CRP, indicating that the CRP/mutant
      interacts with the bound RNA polymerase, which would account for the near
      constancy of the enhancement factors. The corresponding enhancement factors for
      the synlac promoter and a promoter with a different CRP binding site sequence
      (syngal promoter) were also nearly the same, 7.2 +/- 0.7 and 6 +/- 1,
      respectively. The binding reaction of the syncon promoter to the RNA polymerase
      is exothermic, with a binding constant (K(b)) = 2.1 +/- 0. 2 x 10(7) m(-1).

PMID- 10934202
TI  - A cellular protein, hnRNP H, binds to the negative regulator of splicing element
      from Rous sarcoma virus.
AB  - Incomplete RNA splicing is a key feature of the retroviral life cycle. This is in
      contrast to the processing of most cellular pre-mRNAs, which are usually spliced
      to completion. In Rous sarcoma virus, splicing control is achieved in part
      through a cis-acting RNA element termed the negative regulator of splicing (NRS).
      The NRS is functionally divided into two parts termed NRS5' and NRS3', which bind
      a number of splicing factors. The U1 and U11 small nuclear ribonucleoproteins
      interact with sequences in NRS3', whereas NRS5' binds several proteins including
      members of the SR [corrected] family of proteins. Among the proteins that
      specifically bind NRS5' is a previously unidentified 55-kDa protein (p55). In
      this report we describe the isolation and identification of p55. The p55 binding
      site was localized by UV cross-linking to a 31-nucleotide segment, and a protein
      that binds specifically to it was isolated by RNA affinity selection and
      identified by mass spectrometry as hnRNP H. Antibodies against hnRNP H
      immunoprecipitated cross-linked p55 and induced a supershift of a p55-containing
      complex formed in HeLa nuclear extract. Furthermore, UV cross-linking and
      electrophoretic mobility shift assays indicated that recombinant hnRNP H
      specifically interacts with the p55 binding site, confirming that hnRNP H is p55.
      The possible roles of hnRNP H in NRS function are discussed.

PMID- 10934203
TI  - The alpha 3(IV)185-206 peptide from noncollagenous domain 1 of type IV collagen
      interacts with a novel binding site on the beta 3 subunit of integrin alpha Vbeta
      3 and stimulates focal adhesion kinase and phosphatidylinositol 3-kinase
      phosphorylation.
AB  - We have recently identified integrin alpha(v)beta(3) and the associated
      CD47/integrin-associated protein (IAP) together with three other proteins as the
      potential tumor cell receptors for the alpha(3) chain of basement membrane type
      IV collagen (Shahan, T.A., Ziaie, Z., Pasco, S., Fawzi, A., Bellon, G.,
      Monboisse, J. C., and Kefalides, N. A. (1999) Cancer Res. 59, 4584-4590). Using
      different cell lines expressing alpha(v)beta(3), alpha(IIb)beta(3), and/or CD47
      and a liquid phase receptor capture assay, we now provide direct evidence that
      the synthetic and biologically active alpha3(IV)185-206 peptide, derived from the
      alpha3(IV) chain, interacts with the beta(3) subunit of integrin alpha(v)beta(3),
      independently of CD47. Increased alpha3(IV) peptide binding was observed on
      transforming growth factor-beta(1)-stimulated HT-144 cells shown to up-regulate
      alpha(v)beta(3) independently of CD47. Also, incubation of HT-144 melanoma cells
      in suspension induced de novo exposure of ligand-induced binding site epitopes on
      the beta(3) subunit similar to those observed following Arg-Gly-Asp-Ser (RGDS)
      stimulation. However, RGDS did not prevent HT-144 cell attachment and spreading
      on the alpha3(IV) peptide, suggesting that the alpha3(IV) binding domain on the
      beta(3) subunit is distinct from the RGD recognition site. alpha3(IV) peptide
      binding to HT-144 cells in suspension stimulated time-dependent tyrosine
      phosphorylation, while the RGDS peptide did not. Two major phosphotyrosine
      proteins of 120-130 and 85 kDa were immunologically identified as focal adhesion
      kinase and phosphatidylinositol 3-kinase (PI3-kinase). A direct involvement of
      PI3-kinase in alpha3(IV)-dependent beta(3) integrin signaling could be
      documented, since pretreatment of HT-144 cells with wortmannin, a PI3-kinase
      inhibitor, reverted the known inhibitory effect of alpha3(IV) on HT-144 cell
      proliferation as well as membrane type 1-matrix metalloproteinase gene
      expression. These results provide evidence that the alpha3(IV)185-206 peptide, by
      directly interacting with the beta(3) subunit of alpha(v)beta(3), activates a
      signaling cascade involving focal adhesion kinase and PI3-kinase.

PMID- 10934204
TI  - Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase.
      Regulation of MR-GEF by M-Ras-GTP interaction.
AB  - Although the Ras subfamily of GTPases consists of approximately 20 members, only
      a limited number of guanine nucleotide exchange factors (GEFs) that couple
      extracellular stimuli to Ras protein activation have been identified.
      Furthermore, no novel downstream effectors have been identified for the M-Ras/R
      Ras3 GTPase. Here we report the identification and characterization of three Ras
      family GEFs that are most abundantly expressed in brain. Two of these GEFs, MR
      GEF (M-Ras-regulated GEF, KIAA0277) and PDZ-GEF (KIAA0313) bound specifically to
      nucleotide-free Rap1 and Rap1/Rap2, respectively. Both proteins functioned as
      Rap1 GEFs in vivo. A third GEF, GRP3 (KIAA0846), activated both Ras and Rap1 and
      shared significant sequence homology with the calcium- and diacylglycerol
      activated GEFs, GRP1 and GRP2. Similarly to previously identified Rap GEFs, C3G
      and Smg GDS, each of the newly identified exchange factors promoted the
      activation of Elk-1 in the LNCaP prostate tumor cell line where B-Raf can couple
      Rap1 to the extracellular receptor-activated kinase cascade. MR-GEF and PDZ-GEF
      both contain a region immediately N-terminal to their catalytic domains that
      share sequence homology with Ras-associating or RalGDS/AF6 homology (RA) domains.
      By searching for in vitro interaction with Ras-GTP proteins, PDZ-GEF specifically
      bound to Rap1A- and Rap2B-GTP, whereas MR-GEF bound to M-Ras-GTP. C-terminally
      truncated MR-GEF, lacking the GEF catalytic domain, retained its ability to bind
      M-Ras-GTP, suggesting that the RA domain is important for this interaction. Co
      immunoprecipitation studies confirmed the interaction of M-Ras-GTP with MR-GEF in
      vivo. In addition, a constitutively active M-Ras(71L) mutant inhibited the
      ability of MR-GEF to promote Rap1A activation in a dose-dependent manner. These
      data suggest that M-Ras may inhibit Rap1 in order to elicit its biological
      effects.

PMID- 10934205
TI  - Multiple mechanisms underlie neurotoxicity by different types of Alzheimer's
      disease mutations of amyloid precursor protein.
AB  - We examined a neuronal cell system in which single-cell expression of either
      familial Alzheimer's disease (FAD) gene V642I-APP or K595N/M596L-APP (NL-APP) in
      an inducible plasmid was controlled without affecting transfection efficiency.
      This system revealed that (i) low expression of both mutants exerted toxicity
      sensitive to both Ac-DEVD-CHO (DEVD) and glutathione ethyl ester (GEE), whereas
      wild-type APP (wtAPP) only at higher expression levels caused GEE/DEVD-resistant
      death to lesser degrees; (ii) toxicity by the V642I mutation was entirely
      GEE/DEVD sensitive; and (iii) toxicity by higher expression of NL-APP was
      GEE/DEVD resistant. The GEE/DEVD-sensitive death was sensitive to pertussis toxin
      and was due to G(o)-interacting His(657)-Lys(676) domain. The GEE/DEVD-resistant
      death was due to C-terminal Met(677)-Asn(695). APP mutants lacking either domain
      unraveled elaborate intracellular cross-talk between these domains. E618Q-APP,
      responsible for non-AD type of a human disease, only exerted GEE/DEVD-resistant
      death at higher expression. Therefore, (i) different FAD mutations in APP cause
      neuronal cell death through different cytoplasmic domains via different sets of
      mechanisms; (ii) expression levels of FAD genes are critical in activating
      specific death mechanisms; and (iii) toxicity by low expression of both mutants
      most likely reflects the pathogenetic mechanism of FAD.

PMID- 10934206
TI  - Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic
      phospholipase A2-linked cascade.
AB  - Reactive oxygen species (ROS) are important regulatory molecules implicated in
      the signaling cascade triggered by tumor necrosis factor (TNF)-alpha, although
      the events through which TNF-alpha induces ROS generation are not yet well
      characterized. We therefore investigated selected candidates likely to mediate
      TNF-alpha-induced ROS generation. Consistent with the role of Rac in that
      process, stable expression of Rac(Asn-17), a dominant negative Rac1 mutant,
      completely blocked TNF-alpha-induced ROS generation. To understand better the
      mediators downstream of Rac, we investigated the involvement of cytosolic
      phospholipase A(2) (cPLA(2)) activation and metabolism of the resultant
      arachidonic acid (AA) by 5-lipoxygenase (5-LO). TNF-alpha-induced ROS generation
      was blocked by inhibition of cPLA(2) or 5-LO, but not cyclooxygenase, suggesting
      that TNF-alpha-induced ROS generation is dependent on synthesis of AA and its
      subsequent metabolism to leukotrienes. Consistent with that hypothesis, TNF-alpha
      Rac-dependently stimulated endogenous production of leukotriene B(4) (LTB(4)),
      while exogenous application of LTB(4) increased levels of ROS. In contrast,
      application of leukotrienes C(4), D(4), and E(4) or prostaglandin E(2) had little
      effect. Our findings suggest that LTB(4) production by 5-LO is situated
      downstream of the Rac-cPLA(2) cascade, and we conclude that Rac, cPLA(2), and
      LTB(4) play pivotal roles in the ROS-generating cascade triggered by TNF-alpha.

PMID- 10934207
TI  - Lysyl hydroxylase 3 is a multifunctional protein possessing collagen
      glucosyltransferase activity.
AB  - Lysyl hydroxylase (EC ) and glucosyltransferase (EC ) are enzymes involved in
      post-translational modifications during collagen biosynthesis. We reveal in this
      paper that the protein produced by the cDNA for human lysyl hydroxylase isoform 3
      (LH3) has both lysyl hydroxylase and glucosyltransferase (GGT) activities. The
      other known lysyl hydroxylase isoforms, LH1, LH2a, and LH2b, have no GGT
      activity. Furthermore, antibodies recognizing the amino acid sequence of human
      LH3 and those against a highly purified chicken GGT partially inhibited the GGT
      activity. Similarly, a partial inhibition was observed when these antibodies were
      tested against GGT extracted from human skin fibroblasts. In vitro mutagenesis
      experiments demonstrate that the amino acids involved in the GGT active site
      differ from those required for LH3 activity.

PMID- 10934208
TI  - Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type
      2C alpha and beta 2 isoforms.
AB  - We previously reported that the activating phosphorylation on cyclin-dependent
      kinases in yeast (Cdc28p) and in humans (Cdk2) is removed by type 2C protein
      phosphatases. In this study, we characterize this PP2C-like activity in HeLa cell
      extract and determine that it is due to PP2C beta 2, a novel PP2C beta isoform,
      and to PP2C alpha. PP2C alpha and PP2C beta 2 co-purified with Mg(2+)-dependent
      Cdk2/Cdk6 phosphatase activity in DEAE-Sepharose, Superdex-200, and Mono Q
      chromatographies. Moreover, purified recombinant PP2C alpha and PP2C beta 2
      proteins efficiently dephosphorylated monomeric Cdk2/Cdk6 in vitro. The
      dephosphorylation of Cdk2 and Cdk6 by PP2C isoforms was inhibited by the binding
      of cyclins. We found that the PP2C-like activity in HeLa cell extract, partially
      purified HeLa PP2C alpha and PP2C beta 2 isoforms, and the recombinant PP2Cs
      exhibited a comparable substrate preference for a phosphothreonine containing
      substrate, consistent with the conservation of threonine residues at the site of
      activating phosphorylation in CDKs.

PMID- 10934209
TI  - NMR structure and mutagenesis of the third Bir domain of the inhibitor of
      apoptosis protein XIAP.
AB  - The inhibitor of apoptosis proteins (IAPs) regulate the caspase family of
      cysteine proteases, which play an important role in the execution of programmed
      cell death. Human X-linked inhibitor of apoptosis protein (XIAP) is a potent
      inhibitor of caspases-3, -7, and -9. Here we show that the Bir3 domain is the
      minimal region of XIAP that is needed for potent caspase-9 inhibition. The three
      dimensional structure of the Bir3 domain of XIAP, determined by NMR spectroscopy,
      resembles a classical zinc finger and consists of five alpha-helices, a three
      stranded beta-sheet, and a zinc atom chelated to three cysteines and one
      histidine. The structure of the Bir3 domain is similar to that of the Bir2 domain
      of XIAP but differs from the previously determined structure of the Bir3 domain
      of MIHB. Based on site-directed mutagenesis, we have identified the regions of
      the Bir3 domain of XIAP that are important for inhibiting caspase-9. Despite the
      structural similarities of the Bir2 and Bir3 domain of XIAP, a different set of
      residues were found to be critical for inhibiting the individual caspases. These
      results suggest that XIAP inhibits caspase-3 and caspase-9 in a different manner.

PMID- 10934210
TI  - Molecular and cellular properties of the rat AA4 antigen, a C-type lectin-like
      receptor with structural homology to thrombomodulin.
AB  - The murine fetal stem cell marker AA4 has recently been cloned and is known to be
      the homolog of the human phagocytic C1q receptor involved in host defense. We
      herein report the molecular cloning and the cellular expression pattern of the
      rat AA4 antigen. Modular architecture analysis indicated that the rat AA4 is a
      member of C-type lectin-like family and, interestingly, displays similar domain
      composition and organization to thrombomodulin. Northern blot and reverse
      transcriptase-polymerase chain reaction analyses indicated that rat AA4 was
      encoded by a single transcript of 7 kilobases expressed constitutively in all
      tissues. In situ hybridization showed that AA4 was expressed predominantly by
      pneumocytes and vascular endothelial cells. Using an affinity purified polyclonal
      antibody raised against a rat AA4-Fc fusion protein, AA4 was identified as a
      glycosylated protein of 100 kDa expressed by endothelial cells > platelets > NK
      cells and monocytes (ED1+ cells). The staining was associated to the cell surface
      and intracytoplasmic vesicles. Conversely, erythrocytes, T and B lymphocytes,
      neutrophils, and macrophages (ED2+ cells) were consistently negative for AA4. As
      expected, the macrophage cell line NR8383 expressed weak levels of AA4. Taken
      together, our results support the idea that AA4/C1qRp is involved in some cell
      cell interactions.

PMID- 10934211
TI  - The non-competitive antagonists 2-methyl-6-(phenylethynyl)pyridine and 7
      hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester interact with
      overlapping binding pockets in the transmembrane region of group I metabotropic
      glutamate receptors.
AB  - We have investigated the mechanism of inhibition and site of action of the novel
      human metabotropic glutamate receptor 5 (hmGluR5) antagonist 2-methyl-6
      (phenylethynyl)pyridine (MPEP), which is structurally unrelated to classical
      metabotropic glutamate receptor (mGluR) ligands. Schild analysis indicated that
      MPEP acts in a non-competitive manner. MPEP also inhibited to a large extent
      constitutive receptor activity in cells transiently overexpressing rat mGluR5,
      suggesting that MPEP acts as an inverse agonist. To investigate the molecular
      determinants that govern selective ligand binding, a mutagenesis study was
      performed using chimeras and single amino acid substitutions of hmGluR1 and
      hmGluR5. The mutants were tested for binding of the novel mGluR5 radioligand
      [(3)H]2-methyl-6-(3-methoxyphenyl)ethynyl pyridine (M-MPEP), a close analog of
      MPEP. Replacement of Ala-810 in transmembrane (TM) VII or Pro-655 and Ser-658 in
      TMIII with the homologous residues of hmGluR1 abolished radioligand binding. In
      contrast, the reciprocal hmGluR1 mutant bearing these three residues of hmGluR5
      showed high affinity for [(3)H]M-MPEP. Radioligand binding to these mutants was
      also inhibited by 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl
      ester (CPCCOEt), a structurally unrelated non-competitive mGluR1 antagonist
      previously shown to interact with residues Thr-815 and Ala-818 in TMVII of
      hmGluR1. These results indicate that MPEP and CPCCOEt bind to overlapping binding
      pockets in the TM region of group I mGluRs but interact with different non
      conserved residues.

PMID- 10934212
TI  - Cloning and characterization of Xenopus Rsk2, the predominant p90 Rsk isozyme in
      oocytes and eggs.
AB  - The 90-kDa ribosomal S6 kinases, the p90 Rsks, are a family of intracellular
      serine/threonine protein kinases distinguished by two distinct kinase domains.
      Rsks are activated downstream of the ERK1 (p44) and ERK2 (p42) mitogen-activated
      protein (MAP) kinases in diverse biological contexts, including progression
      through meiotic and mitotic M phases in Xenopus oocytes and cycling Xenopus egg
      extracts, and are critical for the M phase functions of Xenopus p42 MAPK. Here we
      report the cloning and biochemical characterization of Xenopus Rsk2. Xenopus Rsk1
      and Rsk2 are specifically recognized by commercially available RSK1 and RSK2
      antisera on immunoblots, but both Rsk1 and Rsk2 are immunoprecipitated by RSK1,
      RSK2, and RSK3 sera. Rsk2 is about 20-fold more abundant than the previously
      described Xenopus Rsk1 protein; their concentrations are approximately 120 and 5
      nm, respectively. Rsk2, like Rsk1, forms a heteromeric complex with p42 MAP
      kinase. This interaction depends on sequences at the extreme C terminus of Rsk2
      and can be disrupted by a synthetic peptide derived from the C-terminal 20 amino
      acids of Rsk2. Finally, we demonstrate that p42 MAP kinase can activate
      recombinant Rsk2 in vitro to a specific activity comparable to that found in Rsk2
      that has been activated maximally in vivo. These findings underscore the
      importance of the Rsk2 isozyme in the M phase functions of p42 MAP kinase and
      provide tools for further examining Rsk2 function.

PMID- 10934213
TI  - Expression and characterization of the naturally occurring mutation L394R in
      human gamma-glutamyl carboxylase.
AB  - Patients with mutation L394R in gamma-glutamyl carboxylase have a severe bleeding
      disorder because of decreased biological activities of all vitamin K-dependent
      coagulation proteins. Vitamin K administration partially corrects this
      deficiency. To characterize L394R, we purified recombinant mutant L394R and wild
      type carboxylase expressed in baculovirus-infected insect cells. By kinetic
      studies, we analyzed the catalytic activity of mutant L394R and its binding to
      factor IX's propeptide and vitamin KH(2). Mutant L394R differs from its wild-type
      counterpart as follows: 1) 110-fold higher K(i) for Boc-mEEV, an active site
      specific, competitive inhibitor of FLEEL; 2) 30-fold lower V(max)/K(m) toward the
      substrate FLEEL in the presence of the propeptide; 3) severely reduced activity
      toward FLEEL carboxylation in the absence of the propeptide; 4) 7-fold decreased
      affinity for the propeptide; 5) 9-fold higher K(m) for FIXproGla, a substrate
      containing the propeptide and the Gla domain of human factor IX; and 6) 5-fold
      higher K(m) for vitamin KH(2). The primary defect in mutant L394R appears to be
      in its glutamate-binding site. To a lesser degree, the propeptide and KH(2)
      binding properties are altered in the L394R mutant. Compared with its wild-type
      counterpart, the L394R mutant shows an augmented activation of FLEEL
      carboxylation by the propeptide.

PMID- 10934215
TI  - Modifications in lignin and accumulation of phenolic glucosides in poplar xylem
      upon down-regulation of caffeoyl-coenzyme A O-methyltransferase, an enzyme
      involved in lignin biosynthesis.
AB  - Caffeoyl-coenzyme A O-methyltransferase (CCoAOMT) methylates, in vitro, caffeoyl
      CoA and 5-hydroxyferuloyl-CoA, two possible precursors in monolignol biosynthesis
      in vivo. To clarify the in vivo role of CCoAOMT in lignin biosynthesis,
      transgenic poplars with 10% residual CCoAOMT protein levels in the stem xylem
      were generated. Upon analysis of the xylem, the affected transgenic lines had a
      12% reduced Klason lignin content, an 11% increased syringyl/guaiacyl ratio in
      the noncondensed lignin fraction, and an increase in lignin-attached p
      hydroxybenzoate but otherwise a lignin composition similar to that of wild type.
      Stem xylem of the CCoAOMT-down-regulated lines had a pink-red coloration, which
      coincided with an enhanced fluorescence of mature vessel cell walls. The reduced
      production of CCoAOMT caused an accumulation of O(3)-beta-d-glucopyranosyl
      caffeic acid, O(4)-beta-d-glucopyranosyl-vanillic acid, and O(4)-beta-d
      glucopyranosyl-sinapic acid (GSA), as authenticated by (1)H NMR. Feeding
      experiments showed that O(3)-beta-d-glucopyranosyl-caffeic acid and GSA are
      storage or detoxification products of caffeic and sinapic acid, respectively. The
      observation that down-regulation of CCoAOMT decreases lignin amount whereas GSA
      accumulates to 10% of soluble phenolics indicates that endogenously produced
      sinapic acid is not a major precursor in syringyl lignin biosynthesis. Our in
      vivo results support the recently obtained in vitro enzymatic data that suggest
      that the route from caffeic acid to sinapic acid is not used for lignin
      biosynthesis.

PMID- 10934214
TI  - Biosynthesis of the galactan component of the mycobacterial cell wall.
AB  - The structural core of the cell walls of Mycobacterium spp. consists of
      peptidoglycan bound by a linker unit (-alpha-L-Rhap-(1-->3)-D-GlcNAc-P-) to a
      galactofuran, which in turn is attached to arabinofuran and mycolic acids. The
      sequence of reactions leading to the biogenesis of this complex starts with the
      formation of the linker unit on a polyprenyl-P to produce polyprenyl-P-P-GlcNAc
      Rha (Mikusova, K., Mikus, M., Besra, G. S., Hancock, I., and Brennan, P. J.
      (1996) J. Biol. Chem. 271, 7820-7828). We now establish that formation of the
      galactofuran takes place on this intermediate with UDP-Galf as the Galf donor
      presented in the form of UDP-Galp and UDP-Galp mutase (the glf gene product) and
      is catalyzed by galactofuranosyl transferases, one of which, the Mycobacterium
      tuberculosis H37Rv3808c gene product, has been identified. Evidence is also
      presented for the growth of the arabinofuran on this polyprenyl-P-P-linker unit
      galactan intermediate catalyzed by unidentified arabinosyl transferases, with
      decaprenyl-P-Araf or 5-P-ribosyl-PP as the Araf donor. The product of these
      steps, the lipid-linked-LU-galactan-arabinan has been partially characterized in
      terms of its heterogeneity, size, and composition. Biosynthesis of the major
      components of mycobacterial cell walls is proving to be extremely complex.
      However, partial definition of arabinogalactan synthesis, the site of action of
      several major anti-tuberculosis drugs, facilitates the present day thrust for new
      drugs to counteract multiple drug-resistant tuberculosis.

PMID- 10934217
TI  - Fatty acid regulation of gene transcription.

PMID- 10934218
TI  - Glucose regulation of gene transcription.

PMID- 10934219
TI  - Sterol regulatory element-binding proteins (SREBPs): key regulators of
      nutritional homeostasis and insulin action.

PMID- 10934220
TI  - Signal transduction by CXC chemokine receptor 4. Stromal cell-derived factor 1
      stimulates prolonged protein kinase B and extracellular signal-regulated kinase 2
      activation in T lymphocytes.
AB  - We report that stromal cell-derived factor (SDF)-1 has the remarkable capacity to
      induce sustained signaling through CXC chemokine receptor 4 (CXCR4). In contrast
      to other chemokines, such as monocyte chemotactic protein 1 (CC chemokine
      receptor 2 [CCR2]), macrophage inflammatory protein 1beta (CCR5), liver and
      activation-regulated chemokine (LARC [CCR6]), Epstein-Barr virus-induced molecule
      1 ligand chemokine (ELC [CCR7]), and IP10 (CXCR3), SDF-1 stimulates the prolonged
      activation of protein kinase B and extracellular signal-regulated kinase (ERK)-2.
      Activation of protein kinase B is reversed by displacement of SDF-1 from CXCR4 or
      inhibition of phosphatidylinositol 3-kinase. Although increasing concentrations
      of SDF-1 enhance CXCR4 internalization, kinase activation is prolonged. In
      addition, restimulation yields >60% of initial protein kinase B activity,
      indicating that the remaining receptors are not desensitized. Furthermore,
      activation is prolonged by inhibiting SDF-1 degradation. The sustained activation
      of cell survival and mitogenic pathways may account for the unique role of SDF-1
      and CXCR4 in embryogenesis and lymphopoiesis.

PMID- 10934221
TI  - Deficiency in the transcription factor interferon regulatory factor (IRF)-2 leads
      to severely compromised development of natural killer and T helper type 1 cells.
AB  - Interferon (IFN) regulatory factor (IRF)-2 was originally described as an
      antagonist of IRF-1-mediated transcriptional regulation of IFN-inducible genes.
      IRF-1(-/)- mice exhibit defective T helper type 1 (Th1) cell differentiation. We
      have used experimental leishmaniasis to show that, like IRF-1(-/)- mice, IRF-2(
      /)- mice are susceptible to Leishmania major infection due to a defect in Th1
      differentiation. Natural killer (NK) cell development is compromised in both IRF
      1(-/)- and IRF-2(-/)- mice, but the underlying mechanism differs. NK (but not
      NK(+) T) cell numbers are decreased in IRF-2(-/)- mice, and the NK cells that are
      present are immature in phenotype. Therefore, like IRF-1, IRF-2 is required for
      normal generation of Th1 responses and for NK cell development in vivo. In this
      particular circumstance the absence of IRF-2 cannot be compensated for by the
      presence of IRF-1 alone. Mechanistically, IRF-2 may act as a functional agonist
      rather than antagonist of IRF-1 for some, but not all, IFN-stimulated regulatory
      element (ISRE)-responsive genes.

PMID- 10934222
TI  - X-linked lymphoproliferative disease. 2B4 molecules displaying inhibitory rather
      than activating function are responsible for the inability of natural killer
      cells to kill Epstein-Barr virus-infected cells.
AB  - 2B4 is a surface molecule involved in activation of the natural killer (NK) cell
      mediated cytotoxicity. It binds a protein termed Src homology 2 domain-containing
      protein (SH2D1A) or signaling lymphocyte activation molecule (SLAM)-associated
      protein (SAP), which in turn has been proposed to function as a regulator of the
      2B4-associated signal transduction pathway. In this study, we analyzed patients
      with X-linked lymphoproliferative disease (XLP), a severe inherited
      immunodeficiency characterized by critical mutations in the SH2D1A gene and by
      the inability to control Epstein-Barr virus (EBV) infections. We show that, in
      these patients, 2B4 not only fails to transduce triggering signals, but also
      mediates a sharp inhibition of the NK-mediated cytolysis. Other receptors
      involved in NK cell triggering, including CD16, NKp46, NKp44, and NKp30,
      displayed a normal functional capability. However, their activating function was
      inhibited upon engagement of 2B4 molecules. CD48, the natural ligand of 2B4, is
      highly expressed on the surface of EBV(+) B cell lines. Remarkably, NK cells from
      XLP patients could not kill EBV(+) B cell lines. This failure was found to be the
      consequence of inhibitory signals generated by the interaction between 2B4 and
      CD48, as the antibody-mediated disruption of the 2B4-CD48 interaction restored
      lysis of EBV(+) target cells lacking human histocompatibility leukocyte antigen
      (HLA) class I molecules. In the case of autologous or allogeneic (HLA class I(+))
      EBV(+) lymphoblastoid cell lines, restoration of lysis was achieved only by the
      simultaneous disruption of 2B4-CD48 and NK receptor-HLA class I interactions.
      Molecular analysis revealed that 2B4 molecules isolated from either XLP or normal
      NK cells were identical. As expected, in XLP-NK cells, 2B4 did not associate with
      SH2D1A, whereas similar to 2B4 molecules isolated from normal NK cells, it did
      associate with Src homology 2 domain-containing phosphatase 1.

PMID- 10934223
TI  - Depletion of CD4(+) T cells causes reactivation of murine persistent tuberculosis
      despite continued expression of interferon gamma and nitric oxide synthase 2.
AB  - Tuberculosis is a major cause of death in much of the world. Current estimates
      are that one-third of the world's population is infected with Mycobacterium
      tuberculosis. Most infected persons control the infection but in many cases may
      not eliminate the organism. Reactivation of this clinically latent infection is
      responsible for a large proportion of active tuberculosis cases. A major risk
      factor for reactivation of latent tuberculosis is HIV infection, suggesting a
      role for the CD4(+) T cell subset in maintaining the latent persistent infection.
      In this study, we tested the requirement for CD4(+) T cells in preventing
      reactivation in a murine model of latent tuberculosis. Antibody-mediated
      depletion of CD4(+) T cells resulted in rapid reactivation of a persistent
      infection, with dramatically increased bacterial numbers in the organs, increased
      pathology in the lungs, and decreased survival. Although CD4(+) T cells are
      believed to be a major source of interferon (IFN)-gamma, expression of the gene
      for IFN-gamma in the lungs of CD4(+) T cell-depleted mice was similar to that in
      control mice. In addition, inducible nitric oxide synthase production and
      activity was unimpaired after CD4(+) T cell depletion, indicating that macrophage
      activation was present even during CD4(+) T cell deficiency. These data indicate
      that CD4(+) T cells are necessary to prevent reactivation but may have roles in
      addition to IFN-gamma production and macrophage activation in controlling a
      persistent tuberculous infection.

PMID- 10934224
TI  - A hierarchical role for classical pathway complement proteins in the clearance of
      apoptotic cells in vivo.
AB  - The strongest susceptibility genes for the development of systemic lupus
      erythematosus (SLE) in humans are null mutants of classical pathway complement
      proteins. There is a hierarchy of disease susceptibility and severity according
      to the position of the missing protein in the activation pathway, with the
      severest disease associated with C1q deficiency. Here we demonstrate, using novel
      in vivo models of apoptotic cell clearance during sterile peritonitis, a similar
      hierarchical role for classical pathway complement proteins in vivo in the
      clearance of apoptotic cells by macrophages. Our results constitute the first
      demonstration of an impairment in the phagocytosis of apoptotic cells by
      macrophages in vivo in a mammalian system. Apoptotic cells are thought to be a
      major source of the autoantigens of SLE, and impairment of their removal by
      complement may explain the link between hereditary complement deficiency and the
      development of SLE.

PMID- 10934225
TI  - Association between kinin B(1) receptor expression and leukocyte trafficking
      across mouse mesenteric postcapillary venules.
AB  - Using intravital microscopy, we examined the role played by B(1) receptors in
      leukocyte trafficking across mouse mesenteric postcapillary venules in vivo. B(1)
      receptor blockade attenuated interleukin (IL)-1beta-induced (5 ng
      intraperitoneally, 2 h) leukocyte-endothelial cell interactions and leukocyte
      emigration ( approximately 50% reduction). The B(1) receptor agonist des
      Arg(9)bradykinin (DABK), although inactive in saline- or IL-8-treated mice,
      caused marked neutrophil rolling, adhesion, and emigration 24 h after challenge
      with IL-1beta (when the cellular response to IL-1beta had subsided). Reverse
      transcriptase polymerase chain reaction and Western blot revealed a temporal
      association between the DABK-induced response and upregulation of mesenteric B(1)
      receptor mRNA and de novo protein expression after IL-1beta treatment. DABK
      induced leukocyte trafficking was antagonized by the B(1) receptor antagonist des
      arg(10)HOE 140 but not by the B(2) receptor antagonist HOE 140. Similarly, DABK
      effects were maintained in B(2) receptor knockout mice. The DABK-induced
      responses involved the release of neuropeptides from C fibers, as capsaicin
      treatment inhibited the responses. Treatment with the neurokinin (NK)(1) and
      NK(3) receptor antagonists attenuated the responses, whereas NK(2), calcitonin
      gene-related peptide, or platelet-activating factor receptor antagonists had no
      effect. Substance P caused leukocyte recruitment that, similar to DABK, was
      inhibited by NK(1) and NK(3) receptor blockade. Mast cell depletion using
      compound 48/80 reduced DABK-induced leukocyte trafficking, and DABK treatment was
      shown histologically to induce mast cell degranulation. DABK-induced trafficking
      was inhibited by histamine H(1) receptor blockade. Our findings provide clear
      evidence that B(1) receptors play an important role in the mediation of leukocyte
      endothelial cell interactions in postcapillary venules, leading to leukocyte
      recruitment during an inflammatory response. This involves activation of C fibers
      and mast cells, release of substance P and histamine, and stimulation of NK(1),
      NK(3), and H(1) receptors.

PMID- 10934226
TI  - The Rho family guanine nucleotide exchange factor Vav-2 regulates the development
      of cell-mediated cytotoxicity.
AB  - Previous pharmacologic and genetic studies have demonstrated a critical role for
      the low molecular weight GTP-binding protein RhoA in the regulation of cell
      mediated killing by cytotoxic lymphocytes. However, a specific Rho family guanine
      nucleotide exchange factor (GEF) that activates this critical regulator of
      cellular cytotoxicity has not been identified. In this study, we provide evidence
      that the Rho family GEF, Vav-2, is present in cytotoxic lymphocytes, and becomes
      tyrosine phosphorylated after the cross-linking of activating receptors on
      cytotoxic lymphocytes and during the generation of cell-mediated killing. In
      addition, we show that overexpression of Vav-2 in cytotoxic lymphocytes enhances
      cellular cytotoxicity, and this enhancement requires a functional Dbl homology
      and Src homology 2 domain. Interestingly, the pleckstrin homology domain of Vav-2
      was found to be required for enhancement of killing through some, but not all
      activating receptors on cytotoxic lymphocytes. Lastly, although Vav and Vav-2
      share significant structural homology, only Vav is able to enhance nuclear factor
      of activated T cells-activator protein 1-mediated gene transcription downstream
      of the T cell receptor. These data demonstrate that Vav-2, a Rho family GEF,
      differs from Vav in the control of certain lymphocyte functions and participates
      in the control of cell-mediated killing by cytotoxic lymphocytes.

PMID- 10934227
TI  - Clonal expansions of CD8(+) T cells dominate the T cell infiltrate in active
      multiple sclerosis lesions as shown by micromanipulation and single cell
      polymerase chain reaction.
AB  - Clonal composition and T cell receptor (TCR) repertoire of CD4(+) and CD8(+) T
      cells infiltrating actively demyelinating multiple sclerosis (MS) lesions were
      determined with unprecedented resolution at the level of single cells. Individual
      CD4(+) or CD8(+) T cells were isolated from frozen sections of lesional tissue by
      micromanipulation and subjected to single target amplification of TCR-beta gene
      rearrangements. This strategy allows the assignment of a TCR variable region (V
      region) sequence to the particular T cell from which it was amplified. Sequence
      analysis revealed that in both cases investigated, the majority of CD8(+) T cells
      belonged to few clones. One of these clones accounted for 35% of CD8(+) T cells
      in case 1. V region sequence comparison revealed signs of selection for common
      peptide specificities for some of the CD8(+) T cells in case 1. In both cases,
      the CD4(+) T cell population was more heterogeneous. Most CD4(+) and CD8(+)
      clones were represented in perivascular infiltrates as well as among parenchymal
      T cells. In case 2, two of the CD8(+) clones identified in brain tissue were also
      detected in peripheral blood. Investigation of the antigenic specificities of
      expanded clones may help to elucidate their functional properties.

PMID- 10934228
TI  - Human monocyte-derived dendritic cells induce naive T cell differentiation into T
      helper cell type 2 (Th2) or Th1/Th2 effectors. Role of stimulator/responder
      ratio.
AB  - The subset of dendritic cells (DCs) and the nature of the signal inducing DC
      maturation determine the capacity of DCs to generate polarized immune responses.
      In this study, we show that the ability of human monocyte-derived DCs (myeloid
      DC(1)) to promote T helper type 1 (Th1) or Th2 differentiation was also found to
      be critically dependent on stimulator/responder ratio. At a low ratio (1:300),
      mature DCs that have been differentiated after inflammatory (Staphylococcus
      aureus Cowan 1 or lipopolysaccharide) or T cell-dependent (CD40 ligand)
      stimulation induced naive T cells to become Th2 (interleukin [IL]-4(+), IL-5(+),
      interferon gamma) effectors. Th2 differentiation was dependent on B7-CD28
      costimulation and enhanced by OX40-OX40 ligand interactions. However, high DC/T
      cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that
      the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant
      since it allows the antigen-presenting cells to initiate an appropriate response
      for the signal received at the peripheral sites. Controlling the number and the
      rate of DC migration to the T cell areas in lymphoid tissues may be important for
      the therapeutic use of DCs.

PMID- 10934229
TI  - Cell-specific transcriptional regulation of human leukotriene B(4) receptor gene.
AB  - Leukotriene B(4) (LTB(4)) is a lipid mediator that activates leukocytes and is
      involved in host defense and inflammation. BLT1, a high-affinity receptor for
      LTB(4) (originally termed BLT), is expressed exclusively in inflammatory cells
      and is inducible in macrophages upon activation. The mechanisms of tissue
      specific expression and induction of BLT1 are important for the understanding of
      mechanism of onset and the potential treatment of inflammatory disorders. Here,
      we report the genomic structure and a promoter analysis of the human BLT1 gene,
      with an emphasis on the mechanism of cell-specific transcription. No TATA or CAAT
      elements exist around the transcription initiation sites, but a GC-rich sequence
      is observed in this region. A reporter gene assay revealed that a region
      approximately 80 basepair upstream from the initiator sequence is required for
      the basal transcription of the BLT1 gene. Sp1 was found to be a major activator
      of basal transcription by electrophoretic mobility shift assays and site-directed
      mutagenesis. The CpG sites of the BLT1 promoter region were highly methylated in
      BLT1-nonexpressing cells, but not methylated in BLT1-expressing cells. Further,
      methylation of this region in vitro inhibited the promoter activity to
      approximately 15% of the control. Thus, methylation at CpG sites in the promoter
      region is important for cell-specific transcription of the BLT1 gene. The
      promoter region of the BLT1 gene is localized within the open reading frame (ORF)
      of the BLT2 gene, which encodes a low-affinity receptor for LTB(4) (Yokomizo, T.,
      K. Kato, K. Terawaki, T. Izumi, and T. Shimizu. 2000. J. Exp. Med. 192:421-431).
      To our knowledge, this is the first example of "promoter in ORF" in higher
      eukaryotes.

PMID- 10934230
TI  - A second leukotriene B(4) receptor, BLT2. A new therapeutic target in
      inflammation and immunological disorders.
AB  - Leukotriene B(4) (LTB(4)) is a potent chemoattractant and activator of both
      granulocytes and macrophages. The actions of LTB(4) appear to be mediated by a
      specific G protein-coupled receptor (GPCR) BLT1, originally termed BLT (Yokomizo,
      T., T. Izumi, K. Chang, Y. Takuwa, and T. Shimizu. 1997. Nature. 387:620-624).
      Here, we report the molecular cloning of a novel GPCR for LTB(4), designated
      BLT2, which binds LTB(4) with a Kd value of 23 nM compared with 1.1 nM for BLT1,
      but still efficiently transduces intracellular signaling. BLT2 is highly
      homologous to BLT1, with an amino acid identity of 45.2%, and its open reading
      frame is located in the promoter region of the BLT1 gene. BLT2 is expressed
      ubiquitously, in contrast to BLT1, which is expressed predominantly in
      leukocytes. Chinese hamster ovary cells expressing BLT2 exhibit LTB(4)-induced
      chemotaxis, calcium mobilization, and pertussis toxin-insensitive inhibition of
      adenylyl cyclase. Several BLT1 antagonists, including U 75302, failed to inhibit
      LTB(4) binding to BLT2. Thus, BLT2 is a pharmacologically distinct receptor for
      LTB(4), and may mediate cellular functions in tissues other than leukocytes. BLT2
      provides a novel target for antiinflammatory therapy and promises to expand our
      knowledge of LTB(4) function. The location of the gene suggests shared
      transcriptional regulation of these two receptors.

PMID- 10934231
TI  - Targeted disruption of the leukotriene B(4) receptor in mice reveals its role in
      inflammation and platelet-activating factor-induced anaphylaxis.
AB  - Leukotrienes are derived from arachidonic acid and serve as mediators of
      inflammation and immediate hypersensitivity. Leukotriene B(4) (LTB(4)) and
      leukotriene C(4) (LTC(4)) act through G protein-coupled receptors LTB(4) receptor
      (BLTR) and Cys-LTR, respectively. To investigate the physiological role of BLTR,
      we produced mice with a targeted disruption of the BLTR gene. Mice deficient for
      BLTR (BLTR(-/-)) developed normally and had no apparent hematopoietic
      abnormalities. Peritoneal neutrophils from BLTR(-/-) mice displayed normal
      responses to the inflammatory mediators C5a and platelet-activating factor (PAF)
      but did not respond to LTB(4) for calcium mobilization or chemotaxis.
      Additionally, LTB(4) elicited peritoneal neutrophil influx in control but not in
      BLTR(-/-) mice. Thus, BLTR is the sole receptor for LTB(4)-induced inflammation
      in mice. Neutrophil influx in a peritonitis model and acute ear inflammation in
      response to arachidonic acid was significantly reduced in BLTR(-/-) mice. In
      mice, intravenous administration of PAF induces immediate lethal anaphylaxis.
      Surprisingly, female BLTR(-/-) mice displayed selective survival (6 of 9; P =
      0.002) relative to male (1 of 11) mice of PAF-induced anaphylaxis. These results
      demonstrate the role of BLTR in leukotriene-mediated acute inflammation and an
      unexpected sex-related involvement in PAF-induced anaphylaxis.

PMID- 10934232
TI  - BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a
      dominant role in eosinophil accumulation in a murine model of peritonitis.
AB  - Leukotriene B(4) (LTB(4)) is a potent chemoattractant active on multiple
      leukocytes, including neutrophils, macrophages, and eosinophils, and is
      implicated in the pathogenesis of a variety of inflammatory processes. A seven
      transmembrane-spanning, G protein-coupled receptor, called BLTR (LTB(4)
      receptor), has recently been identified as an LTB(4) receptor. To determine if
      BLTR is the sole receptor mediating LTB(4)-induced leukocyte activation and to
      determine the role of LTB(4) and BLTR in regulating leukocyte function in
      inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene
      disruption. This mouse reveals that BLTR alone is responsible for LTB(4)-mediated
      leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo.
      Furthermore, despite the apparent functional redundancy with other
      chemoattractant-receptor pairs in vitro, LTB(4) and BLTR play an important role
      in the recruitment and/or retention of leukocytes, particularly eosinophils, to
      the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key
      receptor that mediates LTB(4)-induced leukocyte activation and establishes a
      model to decipher the functional roles of BLTR and LTB(4) in vivo.

PMID- 10934233
TI  - Activating Ly-49D and inhibitory Ly-49A natural killer cell receptors demonstrate
      distinct requirements for interaction with H2-D(d).
AB  - The activating Ly-49D receptor and the inhibitory Ly-49A receptor mediate
      opposing effects on natural killer (NK) cell cytotoxicity after interaction with
      the same major histocompatibility complex ligand, H2-D(d). To compare Ly-49D and
      Ly-49A interactions with H2-D(d), we created mutations in H2-D(d) and examined
      the functional ability of these mutants to activate lysis through Ly-49D or to
      inhibit lysis through Ly-49A. Specific single amino acid changes in either the H2
      D(d) alpha(1) helix or the alpha(2) helix abrogated Ly-49D-mediated cytotoxicity,
      but these changes had no significant effect on Ly-49A-dependent inhibition. Each
      of three alpha(2) domain mutations in the floor of the peptide binding groove
      reduced functional recognition by either Ly-49D or Ly-49A, but all three were
      required to fully abrogate inhibition by Ly-49A. Our studies indicate that Ly
      49D/H2-D(d) interactions require distinct determinants compared with Ly-49A/H2
      D(d) interactions. These differences have important implications for the
      integration of activating and inhibitory signals in NK cells.

PMID- 10934234
TI  - Mast cells can amplify airway reactivity and features of chronic inflammation in
      an asthma model in mice.
AB  - The importance of mast cells in the development of the allergen-induced airway
      hyperreactivity and inflammation associated with asthma remains controversial. We
      found that genetically mast cell-deficient WBB6F(1)-W/W(v) mice that were
      sensitized to ovalbumin (OVA) without adjuvant, then challenged repetitively with
      antigen intranasally, exhibited much weaker responses in terms of bronchial
      hyperreactivity to aerosolized methacholine, lung tissue eosinophil infiltration,
      and numbers of proliferating cells within the airway epithelium than did
      identically treated WBB6F(1)-+/+ normal mice. However, W/W(v) mice that had
      undergone selective reconstitution of tissue mast cells with in vitro-derived
      mast cells of congenic +/+ mouse origin exhibited airway responses that were very
      similar to those of the +/+ mice. By contrast, W/W(v) mice that were sensitized
      with OVA emulsified in alum and challenged with aerosolized OVA exhibited levels
      of airway hyperreactivity and lung tissue eosinophil infiltration that were
      similar to those of the corresponding +/+ mice. Nevertheless, these W/W(v) mice
      exhibited significantly fewer proliferating cells within the airway epithelium
      than did identically treated +/+ mice. These results show that, depending on the
      "asthma model" investigated, mast cells can either have a critical role in, or
      not be essential for, multiple features of allergic airway responses in mice.

PMID- 10934235
TI  - The scent of a phagocyte: Advances on leukotriene b(4) receptors.

PMID- 10934236
TI  - Developmental profile of the changing properties of NMDA receptors at cerebellar
      mossy fiber-granule cell synapses.
AB  - During cerebellar development, granule cells display well characterized changes
      in the expression of NMDA receptor (NMDAR) NR2 subunits, switching from NR2B to
      NR2A and NR2C in mature cells. Although various studies, including experiments on
      mutant mice with one or more NR2 subunit types deleted, suggest that NR2A, NR2B,
      and NR2C subunits contribute to synaptic NMDARs, changes in the properties of the
      mossy fiber EPSC during development have not been fully evaluated. In particular,
      information on NMDAR EPSCs in mature animals is lacking. We have examined
      pharmacological and kinetic properties of NMDARs at mossy fiber-granule cell
      synapses from their formation to maturity [postnatal day 7 (P7)-P40 rats].
      Significant changes were seen in the relative amplitudes of the non-NMDAR- and
      NMDAR-mediated components of the evoked EPSC and in the decay kinetics of the
      latter. The NMDA/non-NMDA ratio was similar at P7, P21, and P40, but showed a
      clear peak at P12. This change coincided with a speeding of the NMDAR EPSC decay,
      accompanied by a decrease in sensitivity to ifenprodil (selective NR2B
      antagonist). By P21, sensitivity of the NMDAR EPSC to Mg(2+) was approximately
      threefold less than that at P12 (IC(50), 76 vs 28 microm), suggesting
      incorporation of the NR2C subunit. However, the predicted slowing of decay
      kinetics to a value more characteristic of NR2C deactivation, was not seen until
      P40. Our data are consistent with the known switch from NR2B to NR2A subunits
      during the first two postnatal weeks, but suggest a gradual incorporation of the
      NR2C subunit that modifies Mg(2+) sensitivity and only later influences EPSC
      kinetics.

PMID- 10934237
TI  - A role for the beta isoform of protein kinase C in fear conditioning.
AB  - The protein kinase C family of enzymes has been implicated in synaptic plasticity
      and memory in a wide range of animal species, but to date little information has
      been available concerning specific roles for individual isoforms of this category
      of kinases. To investigate the role of the beta isoform of PKC in mammalian
      learning, we characterized mice deficient in the PKC beta gene using anatomical,
      biochemical, physiological, and behavioral approaches. In our studies we observed
      that PKC beta was predominantly expressed in the neocortex, in area CA1 of the
      hippocampus, and in the basolateral nucleus of the amygdala. Mice deficient in
      PKC beta showed normal brain anatomy and normal hippocampal synaptic
      transmission, paired pulse facilitation, and long-term potentiation and normal
      sensory and motor responses. The PKC beta knock-out animals exhibited a loss of
      learning, however; they suffered deficits in both cued and contextual fear
      conditioning. The PKC expression pattern and behavioral phenotype in the PKC beta
      knock-out animals indicate a critical role for the beta isoform of PKC in
      learning-related signal transduction mechanisms, potentially in the basolateral
      nucleus of the amygdala.

PMID- 10934238
TI  - Membrane and synaptic actions of halothane on rat hippocampal pyramidal neurons
      and inhibitory interneurons.
AB  - A relatively small number of inhibitory interneurons can control the excitability
      and synchronization of large numbers of pyramidal neurons in hippocampus and
      other cortical regions. Thus, anesthetic modulation of interneurons could play an
      important role during anesthesia. The aim of this study was to investigate
      effects of a general anesthetic, halothane, on membrane and synaptic properties
      of rat hippocampal interneurons. GABA receptor-mediated IPSCs were recorded with
      whole-cell patch-clamp techniques in visually identified CA1 pyramidal cells and
      interneurons located at the border of stratum lacunosum-moleculare and stratum
      radiatum. Halothane (0.35 mm congruent with 1.2 vol%) depressed evoked IPSC
      amplitudes recorded from both pyramidal cells and inhibitory interneurons. Also,
      halothane considerably prolonged the decay time constant of evoked IPSCs in
      pyramidal cells and interneurons. The frequencies of miniature IPSCs were
      increased by halothane (two- to threefold) in both types of neuron. On the other
      hand, halothane effects on resting membrane potentials were variable but minimal
      in both types of neurons. In current-clamp recordings, halothane depressed EPSP
      amplitudes and increased IPSP amplitudes recorded from both types of neurons. In
      addition, halothane increased the failure rate of synaptically evoked action
      potentials. Taken together, these data provide evidence that halothane increases
      GABA(A) receptor-mediated synaptic inhibition between synaptically connected
      interneurons and depresses excitatory transmission, similar to effects observed
      in pyramidal neurons.

PMID- 10934239
TI  - Coactivation of beta-adrenergic and cholinergic receptors enhances the induction
      of long-term potentiation and synergistically activates mitogen-activated protein
      kinase in the hippocampal CA1 region.
AB  - Interactions between noradrenergic and cholinergic receptor signaling may be
      important in some forms of learning. To investigate whether noradrenergic and
      cholinergic receptor interactions regulate forms of synaptic plasticity thought
      to be involved in memory formation, we examined the effects of concurrent beta
      adrenergic and cholinergic receptor activation on the induction of long-term
      potentiation (LTP) in the hippocampal CA1 region. Low concentrations of the beta
      adrenergic receptor agonist isoproterenol (ISO) and the cholinergic receptor
      agonist carbachol had no effect on the induction of LTP by a brief train of 5 Hz
      stimulation when applied individually but dramatically facilitated LTP induction
      when coapplied. Although carbachol did not enhance ISO-induced increases in cAMP,
      coapplication of ISO and carbachol synergistically activated p42 mitogen
      activated protein kinase (p42 MAPK). This suggests that concurrent beta
      adrenergic and cholinergic receptor activation enhances LTP induction by
      activating MAPK and not by additive or synergistic effects on adenylyl cyclase.
      Consistent with this, blocking MAPK activation with MEK inhibitors suppressed the
      facilitation of LTP induction produced by concurrent beta-adrenergic and
      cholinergic receptor activation. Although MEK inhibitors also suppressed the
      induction of LTP by a stronger 5 Hz stimulation protocol that induced LTP in the
      absence of ISO and carbachol, they had no effect on LTP induced by high-frequency
      synaptic stimulation or low-frequency synaptic stimulation paired with
      postsynaptic depolarization. Our results indicate that MAPK activation has an
      important, modulatory role in the induction of LTP and suggest that coactivation
      of noradrenergic and cholinergic receptors regulates LTP induction via convergent
      effects on MAPK.

PMID- 10934240
TI  - Somatostatin-induced regulation of SST(2A) receptor expression and cellsurface
      availability in central neurons: role of receptor internalization.
AB  - To investigate the effects of somatostatin (somatotropin release-inhibiting
      factor, SRIF) on the regulation of SST(2A) receptors in mammalian brain, we
      examined how blockade of SRIF release or stimulation by the SRIF analog [d
      Trp(8)]-SRIF would affect the expression and cell surface availability of SST(2A)
      receptors in rat brain slices. First, we measured the intensity of SST(2A)
      immunoreactivity, using quantitative light microscopic immunocytochemistry, and
      levels of SST(2A) mRNA, using semiquantitative RT-PCR, under conditions of acute
      SRIF release blockade. Incubation of slices from the claustrum or basolateral
      amygdala, two regions previously shown to contain high concentrations of SST(2A)
      receptors, in Ca(2+)-free Ringer's for 40 min induced a decrease in the intensity
      of SST(2A) receptor immunoreactivity and concentration of SST(2A) mRNA as
      compared with control values obtained in Ca(2+)-supplemented Ringer's. These
      effects were counteracted in a dose-dependent manner by the addition of 10-100 nm
      [d-Trp(8)]-SRIF to the Ca(2+)-free medium. Furthermore, both of these effects
      were abolished in the presence of the endocytosis inhibitors phenylarsine oxide
      or hyperosmolar sucrose, suggesting that they were dependent on receptor
      internalization. Electron microscopic immunogold labeling confirmed the existence
      of an agonist-induced internalization of SST(2A) receptors in central neurons. At
      a high (10 microm), but not at a low (10 nm), concentration of agonist this
      internalization resulted in a significant decrease in cell surface receptor
      density, irrespective of the presence of Ca(2+) in the medium. Taken together,
      these results suggest that ligand-induced endocytosis is responsible for rapid
      transcriptional (increase in SST(2A) expression) and trafficking (loss of cell
      surface receptors) events involved in the control of the somatostatinergic
      signal.

PMID- 10934241
TI  - Two distinct Ca(2+)-dependent signaling pathways regulate the motor output of
      cochlear outer hair cells.
AB  - The outer hair cells (OHCs) of the cochlea have an electromotility mechanism,
      based on conformational changes of voltage-sensitive "motor" proteins in the
      lateral plasma membrane. The translocation of electrical charges across the
      membrane that accompanies electromotility imparts a voltage dependency to the
      membrane capacitance. We used capacitance measurements to investigate whether
      electromotility may be influenced by different manipulations known to affect
      intracellular Ca(2+) or Ca(2+)-dependent protein phosphorylation. Application of
      acetylcholine (ACh) to the synaptic pole of isolated OHCs evoked a Ca(2+)
      activated apamin-sensitive outward K(+) current. It also enhanced
      electromotility, probably because of a phosphorylation-dependent decrease of the
      cell's axial stiffness. However, ACh did not change the voltage-dependent
      capacitance either in conventional whole-cell experiments or under perforated
      patch conditions. The effects produced by the Ca(2+) ionophore ionomycin mimicked
      those produced by ACh. Hyperpolarizing shifts of the voltage dependence of
      capacitance and electromotility were induced by okadaic acid, a promoter of
      protein phosphorylation, whereas trifluoperazine and W-7, antagonists of
      calmodulin, caused opposite depolarizing shifts. Components of the protein
      phosphorylation cascade-IP(3) receptors and calmodulin-dependent protein kinase
      type IV-were immunolocalized to the lateral wall of the OHC. Our results suggest
      that two different Ca(2+)-dependent pathways may control the OHC motor output.
      The first pathway modulates cytoskeletal stiffness and can be activated by ACh.
      The second pathway shifts the voltage sensitivity of the OHC electromotile
      mechanism and may be activated by the release of Ca(2+) from intracellular stores
      located in the proximity of the lateral plasma membrane.

PMID- 10934242
TI  - Functional uncoupling of adenosine A(2A) receptors and reduced responseto
      caffeine in mice lacking dopamine D2 receptors.
AB  - Dopamine D(2) receptors (Rs) and adenosine A(2A)Rs are coexpressed on
      striatopallidal neurons, where they mediate opposing actions. In agreement with
      the idea that D(2)Rs tonically inhibit GABA release from these neurons,
      stimulation-evoked GABA release was significantly greater from striatal/pallidal
      slices from D(2)R null mutant (D(2)R(-/-)) than from wild-type (D(2)R(+/+)) mice.
      Release from heterozygous (D(2)R(+/-)) slices was intermediate. However, contrary
      to predictions that A(2A)R effects would be enhanced in D(2)R-deficient mice, the
      A(2A)R agonist CGS 21680 significantly increased GABA release only from
      D(2)R(+/+) slices. CGS 21680 modulation was observed when D(2)Rs were antagonized
      by raclopride, suggesting that an acute absence of D(2)Rs cannot explain the
      results. The lack of CGS 21680 modulation in the D(2)R-deficient mice was also
      not caused by a compensatory downregulation of A(2A)Rs in the striatum or globus
      pallidus. However, CGS 21680 significantly stimulated cAMP production only in
      D(2)R(+/+) striatal/pallidal slices. This functional uncoupling of A(2A)Rs in the
      D(2)R-deficient mice was not explained by reduced expression of G(s), G(olf), or
      type VI adenylyl cyclase. Locomotor activity induced by the adenosine receptor
      antagonist caffeine was significantly less pronounced in D(2)R(-/-) mice than in
      D(2)R(+/+) and D(2)R(+/-) mice, further supporting the idea that D(2)Rs are
      required for caffeine activation. Caffeine increased c-fos only in D(2)R(-/-)
      globus pallidus. The present results show that a targeted disruption of the D(2)R
      reduces coupling of A(2A)Rs on striatopallidal neurons and thereby responses to
      drugs that act on adenosine receptors. They also reinforce the ideas that D(2)Rs
      and A(2A)Rs are functionally opposed and that D(2)R-mediated effects normally
      predominate.

PMID- 10934243
TI  - A novel leg-shaking Drosophila mutant defective in a voltage-gated K(+)current
      and hypersensitive to reactive oxygen species.
AB  - 1,1'-Dimethyl-4,4'-bipyridinium dichloride (methyl viologen; paraquat), an
      herbicide that causes depletion of NADPH and generates excessive reactive oxygen
      species (ROS) in vivo, has been used to screen for ROS-sensitive Drosophila
      mutants. One mutant so isolated, named quiver(1) (qvr(1)), has a leg-shaking
      phenotype. Mutants of the Shaker (Sh), Hyperkinetic (Hk), and ether a go-go (eag)
      genes, which encode different K(+) channel subunits that regulate the A-type K(+)
      current (I(A)) in different ways, exhibit leg shaking under ether anesthesia and
      have heightened metabolic rates and shortened life spans. We found that Sh, Hk,
      and eag mutant flies were all hypersensitive to paraquat. Double-mutant
      combinations among the three channel mutations and qvr(1) had drastically
      enhanced sensitivity to paraquat. Synaptic transmission at the larval
      neuromuscular junction was increased in the qvr(1) mutant to the level of Sh
      mutants. Similar to eag Sh double mutants, double mutants of eag and qvr(1)
      showed striking enhancement in synaptic transmission and a wings-down phenotype,
      the hallmarks of extreme hyperexcitability. Voltage-clamp experiments
      demonstrated that the qvr(1) mutation specifically disrupted the Sh-dependent
      I(A) current without altering the other currents [I(K), Ca(2+)-activated fast
      (I(CF)) and slow (I(CS)) currents, and I(Ca)] in larval muscles. Several
      deficiency strains of the qvr locus failed to complement qvr(1) and confirmed
      that ether-induced leg shaking, reduced I(A) current, and paraquat
      hypersensitivity map to the same locus. Our results suggest that the qvr gene may
      encode a novel K(+) channel-related polypeptide and indicate a strong link
      between a voltage-activated K(+) current and vulnerability to ROS.

PMID- 10934244
TI  - P2X7 receptors in Muller glial cells from the human retina.
AB  - ATP has been shown to be an important extracellular signaling molecule. There are
      two subgroups of receptors for ATP (and other purines and pyrimidines): the
      ionotropic P2X and the G-protein-coupled P2Y receptors. Different subtypes of
      these receptors have been identified by molecular biology, but little is known
      about their functional properties in the nervous system. Here we present data for
      the existence of P2 receptors in Muller (glial) cells of the human retina. The
      cells were studied by immunocytochemistry, electrophysiology, Ca(2+)
      microfluorimetry, and molecular biology. They displayed both P2Y and P2X
      receptors. Freshly enzymatically isolated cells were used throughout the study.
      Although the [Ca(2+)](i) response to ATP was dominated by release from
      intracellular stores, there is multiple evidence that the ATP-induced membrane
      currents were caused by an activation of P2X(7) receptors. Immunocytochemistry
      and single-cell RT-PCR revealed the expression of P2X(7) receptors by Muller
      cells. In patch-clamp studies, we found that (1) benzoyl-benzoyl ATP (BzATP) was
      the most effective agonist to evoke large inward currents and (2) the currents
      were abolished by P2X antagonists; however, (3) long-lasting application of BzATP
      did not cause an opening of large pores in addition to the cationic channels. By
      microfluorimetry it was shown that the P2X receptors mediated a Ca(2+) influx
      that contributed a small component to the total [Ca(2+)](i) response. Activation
      of P2X receptors may modulate the uptake of neurotransmitters from the
      extracellular space by Muller cells in the retina.

PMID- 10934245
TI  - The Lurcher mutation identifies delta 2 as an AMPA/kainate receptor-like channel
      that is potentiated by Ca(2+).
AB  - Neurodegeneration in Lurcher (Lc) mice results from constitutive activation of
      delta 2, a subunit of ionotropic glutamate receptors (GluRs) with unknown natural
      ligands and channel properties. Homo-oligomeric channels of GluR-delta2 with the
      Lurcher mutation (GluR-delta 2(Lc)) expressed in human embryonic kidney 293 cells
      showed a doubly rectifying current-voltage relation reminiscent of the block by
      intracellular polyamines in AMPA/kainate channels. Similarly, the fraction of the
      total current carried by Ca(2+) was approximately 2-3%, comparable with that
      found in Ca(2+)-permeable AMPA/kainate channels. Currents through GluR-delta
      2(Lc) channels were also potentiated by extracellular Ca(2+) in a biphasic
      manner, with maximal potentiation occurring at physiological concentrations of
      Ca(2+). We examined the functional role of the Q/R site in GluR-delta 2(Lc) by
      replacing glutamine with arginine. Analogous to AMPA/kainate receptors, GluR
      delta 2(Lc)(R) channels showed no voltage-dependent block by intracellular
      polyamines and were nominally impermeable to Ca(2+). The potentiation by Ca(2+),
      however, remained intact. Hence, GluR-delta 2(Lc) channels are functionally
      similar to the AMPA/kainate receptor channels, consistent with the high-sequence
      identity shared by these subunits within the channel-lining M2 and M3 segments.
      Furthermore, potentiation by Ca(2+) and a permeability to Ca(2+) comparable with
      that of AMPA/kainate receptors provide a possible cause for cell death in Lurcher
      mice and may contribute to cerebellar long-term depression under physiological
      conditions.

PMID- 10934246
TI  - Genetically similar transduction mechanisms for touch and hearing in Drosophila.
AB  - To test the effects of mechanosensory mutations on hearing in Drosophila, we have
      recorded sound-evoked potentials originating from ciliated sensory neurons in
      Johnston's organ, the chordotonal organ that is the sensory element of the fly's
      antennal ear. Electrodes inserted close to the antennal nerve were used to record
      extracellular compound potentials evoked by near-field sound stimuli. Sound
      evoked potentials are absent in atonal mutant flies, which lack Johnston's organ.
      Mutations in many genes involved in mechanotransduction by tactile bristles also
      eliminate or reduce the Johnston's organ response, indicating that related
      transduction mechanisms operate in each type of mechanosensory organ. In
      addition, the sound-evoked response is affected by two mutations that do not
      affect bristle mechanotransduction, beethoven (btv) and touch-insensitive-larvaB
      (tilB). btv shows defects in the ciliary dilation, an elaboration of the axoneme
      that is characteristic of chordotonal cilia. tilB, which also causes male
      sterility, shows structural defects in sperm flagellar axonemes. This suggests
      that in addition to the shared transduction mechanism, axonemal integrity and
      possibly ciliary motility are required for signal amplification or transduction
      by chordotonal sensory neurons.

PMID- 10934247
TI  - The Ets transcription factor GABP is required for postsynaptic differentiation in
      vivo.
AB  - At chemical synapses, neurotransmitter receptors are concentrated in the
      postsynaptic membrane. During the development of the neuromuscular junction,
      motor neurons induce aggregation of acetylcholine receptors (AChRs) underneath
      the nerve terminal by the redistribution of existing AChRs and preferential
      transcription of the AChR subunit genes in subsynaptic myonuclei. Neural agrin,
      when expressed in nonsynaptic regions of muscle fibers in vivo, activates both
      mechanisms resulting in the assembly of a fully functional postsynaptic
      apparatus. Several lines of evidence indicate that synaptic transcription of AChR
      genes is primarily dependent on a promoter element called N-box. The Ets-related
      transcription factor growth-associated binding protein (GABP) binds to this motif
      and has thus been suggested to regulate synaptic gene expression. Here, we
      assessed the role of GABP in synaptic gene expression and in the formation of
      postsynaptic specializations in vivo by perturbing its function during
      postsynaptic differentiation induced by neural agrin. We find that neural agrin
      mediated activation of the AChR epsilon subunit promoter is abolished by the
      inhibition of GABP function. Importantly, the number of AChR aggregates formed in
      response to neural agrin was strongly reduced. Moreover, aggregates of
      acetylcholine esterase and utrophin, two additional components of the
      postsynaptic apparatus, were also reduced. Together, these results are the first
      direct in vivo evidence that GABP regulates synapse-specific gene expression at
      the neuromuscular junction and that GABP is required for the formation of a
      functional postsynaptic apparatus.

PMID- 10934248
TI  - A novel SNAP25-caveolin complex correlates with the onset of persistent synaptic
      potentiation.
AB  - We have identified synaptic protein complexes in intact rat hippocampal slices
      using the rapid chemical cross-linking reagent paraformaldehyde. Cellular
      proteins were rapidly cross-linked, solubilized, separated electrophoretically by
      SDS-PAGE, and then identified immunologically. Multiple complexes containing
      syntaxin, the synaptosomal-associated protein of 25 kDa (SNAP25), and vesicle
      associated membrane protein (VAMP) were observed to coexist in a single
      hippocampal slice including a 100 kDa cross-linked protein complex that exhibited
      the same electrophoretic migration as a member of the previously identified SDS
      resistant soluble N-ethylmaleimide-sensitive fusion attachment protein receptor
      "core" of the 20 S complex. A VAMP-synaptophysin complex, reported previously in
      vitro, was also observed in the hippocampal slices. This study links biochemical
      and physiological studies involving presynaptic proteins implicated in secretion
      and confirms that these proteins that have been studied extensively previously in
      the presence of detergent do form "bona fide" cellular complexes. Importantly, we
      have also detected additional novel protein complexes that do not correspond to
      complexes identified previously in vitro. After the induction of persistent
      synaptic potentiation, an abundant 40 kDa SNAP25-caveolin1 complex was observed.
      The SNAP25-caveolin1 complex was not abundant in control slices and, therefore,
      represents the first demonstration of a reorganization of protein complexes in
      intact hippocampal slices during the induction of synaptic potentiation. The
      interaction between caveolin1 and SNAP25 was confirmed biochemically by
      demonstration of the association of caveolin with recombinant-immobilized SNAP25
      and by the coimmunoprecipitation of SNAP25 using caveolin-specific antisera.
      Caveolin1, like SNAP25, was observed to be abundant in isolated hippocampal nerve
      terminals (synaptosomes). Immunofluorescent studies demonstrated that both SNAP25
      and caveolin1 are present in neurons and colocalize in axonal varicosities. These
      results suggest that a short-lasting SNAP25-caveolin interaction may be involved
      in the early phase of synaptic potentiation.

PMID- 10934249
TI  - F-actin is concentrated in nonrelease domains at frog neuromuscular junctions.
AB  - To gain insight into the role of F-actin in the organization of synaptic vesicles
      at release sites, we examined the synaptic distribution of F-actin by using a
      unique synaptic preparation of frog target-deprived nerve terminals. In this
      preparation, imaging of the synaptic site was unobstructed by the muscle fiber
      cytoskeleton, allowing for the examination of hundreds of synaptic sites in their
      entirety in whole mounts. At target-deprived synaptic sites F-actin was
      distributed in a ladder-like pattern and was colocalized with beta-fodrin.
      Surprisingly, F-actin stain, which we localized to the nerve terminal itself, did
      not overlap a synaptic vesicle marker, suggesting that it was concentrated in
      nonrelease domains of nerve terminals between clusters of synaptic vesicles.
      These findings suggest that the majority of the presynaptic F-actin is not
      involved in tethering synaptic vesicles. Instead, the strategic presynaptic
      positioning of this cytoskeletal meshwork in nonrelease domains of the nerve
      terminal suggests alternate functions such as restricting synaptic vesicles to
      release domains, recycling synaptic vesicles, or stabilizing the nerve terminal.

PMID- 10934250
TI  - The weaver mutation reverses the function of dopamine and GABA in mouse
      dopaminergic neurons.
AB  - In the present study, we characterized the intrinsic electrophysiological
      properties and the membrane currents activated by dopamine (DA) D(2) and GABA(B)
      receptors in midbrain dopaminergic neurons, maintained in vitro in a slice
      preparation, from wild-type and homozygous weaver (wv/wv) mice. By using patch
      clamp techniques, we found that membrane potential, apparent input resistance,
      and spontaneous firing of wv/wv dopaminergic neurons were similar to those of
      dopamine-containing cells recorded from nonaffected (+/+) animals. More
      interestingly, the wv/wv neurons were excited rather than inhibited by dopamine
      and the GABA(B) agonist baclofen. This neurotransmitter-mediated excitation was
      attributable to the activation of a G-protein-gated inward current that reversed
      polarity at a membrane potential of approximately -30 mV. We suggest that the
      altered behavior of the receptor-operated wv G-protein-gated inwardly rectifying
      K(+) channel 2 (GIRK2) might be related to the selective degeneration of the
      dopaminergic neurons. In addition, the wv GIRK2 would not only suppress the
      autoreceptor-mediated feedback inhibition of DA release but could also establish
      a feedforward mechanism of DA release in the terminal fields.

PMID- 10934251
TI  - Neuropathology in mice expressing human alpha-synuclein.
AB  - The presynaptic protein alpha-synuclein is a prime suspect for contributing to
      Lewy pathology and clinical aspects of diseases, including Parkinson's disease,
      dementia with Lewy bodies, and a Lewy body variant of Alzheimer's disease. alpha
      Synuclein accumulates in Lewy bodies and Lewy neurites, and two missense
      mutations (A53T and A30P) in the alpha-synuclein gene are genetically linked to
      rare familial forms of Parkinson's disease. Under control of mouse Thy1
      regulatory sequences, expression of A53T mutant human alpha-synuclein in the
      nervous system of transgenic mice generated animals with neuronal alpha
      synucleinopathy, features strikingly similar to those observed in human brains
      with Lewy pathology, neuronal degeneration, and motor defects, despite a lack of
      transgene expression in dopaminergic neurons of the substantia nigra pars
      compacta. Neurons in brainstem and motor neurons appeared particularly
      vulnerable. Motor neuron pathology included axonal damage and denervation of
      neuromuscular junctions in several muscles examined, suggesting that alpha
      synuclein interfered with a universal mechanism of synapse maintenance. Thy1
      transgene expression of wild-type human alpha-synuclein resulted in similar
      pathological changes, thus supporting a central role for mutant and wild-type
      alpha-synuclein in familial and idiotypic forms of diseases with neuronal alpha
      synucleinopathy and Lewy pathology. These mouse models provide a means to address
      fundamental aspects of alpha-synucleinopathy and test therapeutic strategies.

PMID- 10934252
TI  - Expression of GAP-43 and SCG10 mRNAs in lateral geniculate nucleus of normal and
      monocularly deprived macaque monkeys.
AB  - We performed nonradioactive in situ hybridization histochemistry (ISH) in the
      lateral geniculate nucleus (LGN) of the macaque monkey to investigate the
      distribution of mRNA for two growth-associated proteins, GAP-43 and SCG10. GAP-43
      and SCG10 mRNAs were coexpressed in most neurons of both magnocellular layers
      (layers I and II) and parvocellular layers (layers III-VI). Double-labeling using
      nonradioactive ISH and immunofluorescence revealed that both GAP-43 and SCG10
      mRNAs were coexpressed with the alpha-subunit of type II calcium/calmodulin
      dependent protein kinase, indicating that both mRNAs are expressed also in
      koniocellular neurons in the LGN. We also showed that GABA-immunoreactive neurons
      in the LGN did not contain GAP-43 and SCG10 mRNAs, indicating that neither GAP-43
      nor SCG10 mRNAs were expressed in inhibitory interneurons in the LGN. GABA
      immunoreactive neurons in the perigeniculate nucleus, however, contained both GAP
      43 and SCG10 mRNAs, indicating that both mRNAs were expressed in inhibitory
      neurons in the perigeniculate nucleus, which project to relay neurons in the LGN.
      Furthermore, to determine whether the expression of GAP-43 and SCG10 mRNAs is
      regulated by visual input, we performed nonradioactive ISH in the LGN and the
      primary visual area of monkeys deprived of monocular visual input by intraocular
      injections of tetrodotoxin. Both mRNAs were downregulated in the LGN after
      monocular deprivation for 5 d or longer. From these results, we conclude that
      both GAP-43 and SCG10 mRNAs are expressed in the excitatory relay neurons of the
      monkey LGN in an activity-dependent manner.

PMID- 10934253
TI  - Cysteine-string protein increases the calcium sensitivity of neurotransmitter
      exocytosis in Drosophila.
AB  - Previous studies suggest that the vesicular cysteine-string protein (CSP) may
      modulate presynaptic Ca(2+) channel activity in fast neurotransmitter release. To
      test this hypothesis, we analyzed the dynamics of presynaptic Ca(2+) ion influx
      with the Ca(2+) indicator fluo-4 AM at csp mutant neuromuscular junctions of
      Drosophila. From 24 to 30 degrees C, stimulus-evoked, relative presynaptic Ca(2+)
      signals were increasingly larger in csp mutant boutons than in controls. Above 30
      degrees C, Ca(2+) signals declined and were similar to controls at 34 degrees C.
      A prolonged decay of Ca(2+) signals in mutant boutons at high temperatures
      indicated abnormally slow Ca(2+) clearance. Cytosolic Ca(2+) at rest was
      determined with the ratiometric Ca(2+) indicator fura-2 AM and was similar in
      mutant and control boutons at 24 degrees C but higher in mutant boutons at 34
      degrees C. Despite larger Ca(2+) signals in mutant boutons, evoked
      neurotransmitter release was always reduced in csp mutants and exhibited
      pronounced facilitation. Thus, a lack of Ca(2+) entry cannot explain the
      reduction of neurotransmitter release in csp mutants. At all temperatures tested,
      raising extracellular Ca(2+) increased transmitter release elicited by single
      stimuli in csp mutants. Collectively, these data suggest multiple functions for
      CSP at synaptic terminals. Increased Ca(2+) signals coupled with reduced release
      suggest a direct function of CSP in exocytosis downstream from Ca(2+) entry.
      Because the reduction of evoked release in csp mutants is counteracted by
      increased Ca(2+) levels, we suggest that CSP primarily increases the Ca(2+)
      sensitivity of the exocytotic machinery.

PMID- 10934254
TI  - The A53T alpha-synuclein mutation increases iron-dependent aggregation and
      toxicity.
AB  - Parkinson's disease (PD) is the most common motor disorder affecting the elderly.
      PD is characterized by the formation of Lewy bodies and death of dopaminergic
      neurons. The mechanisms underlying PD are unknown, but the discoveries that
      mutations in alpha-synuclein can cause familial PD and that alpha-synuclein
      accumulates in Lewy bodies suggest that alpha-synuclein participates in the
      pathophysiology of PD. Using human BE-M17 neuroblastoma cells overexpressing wild
      type, A53T, or A30P alpha-synuclein, we now show that iron and free radical
      generators, such as dopamine or hydrogen peroxide, stimulate the production of
      intracellular aggregates that contain alpha-synuclein and ubiquitin. The
      aggregates can be identified by immunocytochemistry, electron microscopy, or the
      histochemical stain thioflavine S. The amount of aggregation occurring in the
      cells is dependent on the amount of alpha-synuclein expressed and the type of
      alpha-synuclein expressed, with the amount of alpha-synuclein aggregation
      following a rank order of A53T > A30P > wild-type > untransfected. In addition to
      stimulating aggregate formation, alpha-synuclein also appears to induce toxicity.
      BE-M17 neuroblastoma cells overexpressing alpha-synuclein show up to a fourfold
      increase in vulnerability to toxicity induced by iron. The vulnerability follows
      the same rank order as for aggregation. These data raise the possibility that
      alpha-synuclein acts in concert with iron and dopamine to induce formation of
      Lewy body pathology in PD and cell death in PD.

PMID- 10934255
TI  - Integrin alpha(1) beta(1)-mediated activation of cyclin-dependent kinase 5
      activity is involved in neurite outgrowth and human neurofilament protein H Lys
      Ser-Pro tail domain phosphorylation.
AB  - Cellular adhesion to the extracellular matrix is mediated by a diverse class of
      alpha/beta heterodimeric receptors known as integrins, which transduce signals to
      activate multiple intracellular signal transduction pathways within the cells.
      The signaling pathway linking integrins to mediate neuronal process outgrowth is
      not well understood. Here, we have provided evidence that intracellular signaling
      by the alpha(1)beta(1) integrin-induced activation of cyclin-dependent kinase 5
      (cdk5) is involved in neurite outgrowth and human neurofilament protein H (hNF-H)
      Lys-Ser-Pro (KSP) tail domain phosphorylation in differentiated human SH-SY5Y
      cells. The integrin alpha(1) and beta(1) monoclonal antibodies and BL-1, a
      specific cdk5 inhibitor, inhibited these effects. We also demonstrated that cdk5
      activity and hNF-H KSP tail domain phosphorylation were increased in cdk5/p35 and
      hNF-H tail domain co-transfected HEK293 cells grown on laminin. This increased
      hNF-H tail domain phosphorylation was triggered by cdk5 activation. Taken
      together, these results indicated that cdk5 may play an important role in
      promoting neurite outgrowth and hNF-H tail KSP domain phosphorylation through the
      integrin alpha(1)beta(1) signaling pathway.

PMID- 10934257
TI  - Nerve terminals form but fail to mature when postsynaptic differentiation is
      blocked: in vivo analysis using mammalian nerve-muscle chimeras.
AB  - To better understand the role of the postsynaptic cell in the differentiation of
      presynaptic terminals, we transplanted muscles that lacked postsynaptic
      differentiation from mutant mice into normal adult immunocompatible hosts and
      attached the host nerve to the grafts. Host motor axons innervated wild-type
      grafted muscle fibers and established normal appearing chimeric neuromuscular
      junctions. By repeated in vivo imaging, we found that these synapses were stably
      maintained. Results were different when nerves entered transplanted muscles
      derived from mice lacking muscle-specific receptor tyrosine kinase (MuSK) or
      rapsyn, muscle-specific components required for postsynaptic differentiation.
      Initial steps in presynaptic differentiation (e.g., formation of rudimentary
      arbors and vesicle clustering at terminals) occurred when wild-type neurites
      contacted MuSK- or rapsyn deficient muscle fibers, either in vivo or in vitro.
      However, wild-type terminals contacting MuSK or rapsyn mutant muscle fibers were
      unable to mature, even when the chimeras were maintained for up to 7 months.
      Moreover, in contrast to the stability of wild-type synapses, wild-type nerve
      terminals in mutant muscles underwent continuous remodeling. These results
      suggest that postsynaptic cells supply two types of signals to motor axons: ones
      that initiate presynaptic differentiation and others that stabilize the immature
      contacts so that they can mature. Normal postsynaptic differentiation appears to
      be dispensable for initial stages of presynaptic differentiation but required for
      presynaptic maturation.

PMID- 10934256
TI  - Origin and molecular specification of striatal interneurons.
AB  - The striatum, the largest component of the basal ganglia, contains projection
      neurons and interneurons. Whereas there is considerable agreement that the
      lateral ganglionic eminence (LGE) is the origin of striatal projection neurons,
      less is known about the origin of striatal interneurons. Using focal injections
      of retrovirus into the ventral telencephalon in vitro, we demonstrate that most
      striatal interneurons tangentially migrate from the medial ganglionic eminence
      (MGE) or the adjacent preoptic/anterior entopeduncular areas (POa/AEP) and
      express the NKX2.1 homeodomain protein. Although the majority of striatal
      interneurons (cholinergic, calretinin(+), and parvalbumin(+)) maintain the
      expression of NKX2.1 into adulthood, most of the interneurons expressing
      somatostatin (SOM), neuropeptide Y (NPY), and neural nitric oxide synthase (NOS)
      appear to downregulate the expression of NKX2.1 as they exit the neuroepithelium.
      Analysis of striatal development in mice lacking Nkx2.1 suggests that this gene
      is required for the specification of nearly all striatal interneurons. Similar
      analysis of mice lacking the Mash1 basic helix-loop-helix (bHLH) or both the Dlx1
      and Dlx2 homeodomain transcription factors demonstrates that these genes are
      required for the differentiation of striatal interneurons. Mash1 mutants
      primarily have a reduction in early-born striatal interneurons, whereas Dlx1/2
      mutants primarily have reduced numbers of late-born striatal interneurons. We
      also present evidence implicating the Lhx6 and Lhx7 LIM-homeobox genes in the
      development of distinct interneuron subtypes. Finally, we hypothesize that,
      within the MGE, radially migrating cells generally become projection neurons,
      whereas tangentially migrating cells mainly form interneurons of the striatum and
      cerebral cortex.

PMID- 10934258
TI  - Antisense suppression of potassium channel expression demonstrates its role in
      maturation of the action potential.
AB  - A developmental increase in delayed rectifier potassium current (I(Kv)) in
      embryonic Xenopus spinal neurons is critical for the maturation of excitability
      and action potential waveform. Identifying potassium channel genes that generate
      I(Kv) is essential to understanding the mechanisms by which they are controlled.
      Several Kv genes are upregulated during embryogenesis in parallel with increases
      in I(Kv) and produce delayed rectifier current when heterologously expressed,
      indicating that they could encode channels underlying this current. We used
      antisense (AS) cRNA to test the contribution of xKv3.1 to the maturation of
      I(Kv), because xKv3.1 AS appears to suppress specifically heterologous expression
      of potassium current by xKv3.1 mRNA. The injection of xKv3.1 AS into embryos
      reduces endogenous levels of xKv3.1 mRNA in the developing spinal cord and
      reduces the amplitude and rate of activation of I(Kv) in 40% of cultured neurons,
      similar to the percentage of neurons in which endogenous xKv3.1 transcripts are
      detected. The current in these mature neurons resembles that at an earlier stage
      of differentiation before the appearance of xKv3.1 mRNA. Furthermore, AS
      expression increases the duration of the action potential in 40% of the neurons.
      No change in voltage-dependent calcium current is observed, suggesting that the
      decrease in I(Kv) is sufficient to account for lengthening of the action
      potential. Computer-simulated action potentials incorporating observed reductions
      in amplitude and rate of activation of I(Kv) exhibit an increase in duration
      similar to that observed experimentally. Thus xKv3.1 contributes to the
      maturation of I(Kv) in a substantial percentage of these developing spinal
      neurons.

PMID- 10934259
TI  - Unique expression patterns of cell fate molecules delineate sequential stages of
      dentate gyrus development.
AB  - The dentate gyrus of the hippocampus is uniquely organized with a displaced
      proliferative zone that continues to generate dentate granule cells throughout
      life. We have analyzed the expression of Notch receptors, Notch ligands, and
      basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine
      whether the need to maintain a pool of undifferentiated precursors is reflected
      in the patterns of expression of these genes. Many of these genes are expressed
      diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in
      the rat, just preceding the migration of newly born granule cells and dentate
      precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and
      Id3 expression are all concentrated in the area that specifically gives rise to
      granule cells and dentate precursor cells. Two days later, at the time of
      migration of the first granule cells and dentate precursor cells, cells
      expressing Mash1 are seen in the migratory route from the subventricular zone to
      the developing dentate gyrus. Newly born granule cells expressing NeuroD are also
      present in this migratory pathway. In the first postnatal week, precursor cells
      expressing Mash1 reside in the dentate hilus, and by the third postnatal week
      they have largely taken up their final position in the subgranular zone along the
      hilar side of the dentate granule cell layer. After terminal differentiation,
      granule cells born in the hilus or the subgranular zone begin to express NeuroD
      followed by NeuroD2. This study establishes that the expression patterns of bHLH
      mRNAs evolve during the formation of the dentate gyrus, and the precursor cells
      resident in the mature dentate gyrus share features with precursor cells found in
      development. Thus, many of the same mechanisms that are known to regulate cell
      fate and precursor pool size in other brain regions are likely to be operative in
      the dentate gyrus at all stages of development.

PMID- 10934260
TI  - A critical period for nicotine-induced disruption of synaptic development in rat
      auditory cortex.
AB  - Cholinergic markers in the middle layers of rat auditory cortex are transiently
      upregulated during the second postnatal week, at which time alpha 7 nicotinic
      acetylcholine receptors (nAChRs) selectively regulate NMDA receptor (NMDAR)
      mediated EPSPs. To investigate the developmental role of this regulation, we
      determined whether manipulating nAChR function at specific times during the first
      4 weeks after birth could alter subsequent neuronal function. Rat pups were
      injected twice daily with nicotine (1 or 2 mg/kg) or saline during approximately
      the first, second, or fourth postnatal week (i. e., before, during, or after the
      peak upregulation of nAChRs). Glutamate EPSPs and intrinsic membrane properties
      were measured during whole-cell recordings from visually identified pyramidal
      neurons in layers II-IV of brain slices prepared at least 15 hr after the last
      injection. Chronic nicotine exposure (CNE) had little effect on intrinsic
      membrane properties and during week 1 or 4 did not affect synaptic function.
      However, CNE during week 2 resulted in EPSPs with long durations, multiple peaks,
      and enhanced NMDAR components. These changes remained significant even 10 d after
      CNE. Rapid application of nicotine, which in control neurons selectively enhances
      NMDAR EPSPs during week 2, produced only weak effects after CNE. Receptor binding
      studies showed that CNE-induced EPSP alterations occurred in the absence of
      altered alpha 7 nAChR numbers or agonist binding affinity. Thus, altered
      stimulation of nAChRs by CNE during week 2, but not before or after, disrupts the
      development of glutamate synapses in rat auditory cortex.

PMID- 10934261
TI  - Reduction of neuromuscular activity is required for the rescue of motoneurons
      from naturally occurring cell death by nicotinic-blocking agents.
AB  - Spinal motoneurons (MNs) in the chick embryo undergo programmed cell death
      coincident with the establishment of nerve-muscle connections and the onset of
      synaptic transmission at the neuromuscular junction. Chronic treatment of embryos
      during this period with nicotinic acetylcholine receptor (nAChR)-blocking agents
      [e.g., curare or alpha-bungarotoxin (alpha-BTX)] prevents the death of MNs.
      Although this rescue effect has been attributed previously to a peripheral site
      of action of the nAChR-blocking agents at the neuromuscular junction (NMJ),
      because nAChRs are expressed in both muscle and spinal cord, it has been
      suggested that the rescue effect may, in fact, be mediated by a direct central
      action of nAChR antagonists. By using a variety of different nAChR-blocking
      agents that target specific muscle or neuronal nAChR subunits, we find that only
      those agents that act on muscle-type receptors block neuromuscular activity and
      rescue MNs. However, paralytic, muscular dysgenic mutant chick embryos also
      exhibit significant increases in MN survival that can be further enhanced by
      treatment with curare or alpha-BTX, suggesting that muscle paralysis may not be
      the sole factor involved in MN survival. Taken together, the data presented here
      support the argument that, in vivo, nAChR antagonists promote the survival of
      spinal MNs primarily by acting peripherally at the NMJ to inhibit synaptic
      transmission and reduce or block muscle activity. Although a central action of
      these agents involving direct perturbations of MN activity may also play a
      contributory role, further studies are needed to determine more precisely the
      relative roles of central versus peripheral sites of action in MN rescue.

PMID- 10934262
TI  - FGF/FGFR-2(IIIb) signaling is essential for inner ear morphogenesis.
AB  - Interactions between FGF10 and the IIIb isoform of FGFR-2 appear to be crucial
      for the induction and growth of several organs, particularly those that involve
      budding morphogenesis. We determined their expression patterns in the inner ear
      and analyzed the inner ear phenotype of mice specifically deleted for the IIIb
      isoform of FGFR-2. FGF10 and FGFR-2(IIIb) mRNAs showed distinct, largely
      nonoverlapping expression patterns in the undifferentiated otic epithelium.
      Subsequently, FGF10 mRNA became confined to the presumptive cochlear and
      vestibular sensory epithelia and to the neuronal precursors and neurons. FGFR
      2(IIIb) mRNA was expressed in the nonsensory epithelium of the otocyst that gives
      rise to structures such as the endolymphatic and semicircular ducts. These data
      suggest that in contrast to mesenchymal-epithelial-based FGF10 signaling
      demonstrated for other organs, the inner ear seems to depend on paracrine signals
      that operate within the epithelium. Expression of FGF10 mRNA partly overlapped
      with FGF3 mRNA in the sensory regions, suggesting that they may form parallel
      signaling pathways within the otic epithelium. In addition, hindbrain-derived
      FGF3 might regulate otocyst morphogenesis through FGFR-2(IIIb). Targeted deletion
      of FGFR-2(IIIb) resulted in severe dysgenesis of the cochleovestibular
      membraneous labyrinth, caused by a failure in morphogenesis at the otocyst stage.
      In addition to the nonsensory epithelium, sensory patches and the
      cochleovestibular ganglion remained at a rudimentary stage. Our findings provide
      genetic evidence that signaling by FGFR-2(IIIb) is critical for the morphological
      development of the inner ear.

PMID- 10934263
TI  - Spatial-temporal distribution of whisker-evoked activity in rat somatosensory
      cortex and the coding of stimulus location.
AB  - Rats use their facial vibrissae ("whiskers") to locate and identify objects. To
      learn about the neural coding of contact between whiskers and objects, we
      investigated the representation of single-vibrissa deflection by populations of
      cortical neurons. Microelectrode arrays, arranged in a geometric 10 x 10 grid,
      were inserted into the thalamo-recipient layers of "barrel cortex" (the vibrissal
      region of somatosensory cortex) in urethane-anesthetized rats, and neuronal
      activity across large sets of barrel-columns was measured. Typically, 5 msec
      after deflection of a whisker a 0.2 mm(2) focus of activity emerged. It rapidly
      expanded, doubling in size by 7 msec, before retracting and disappearing 28-59
      msec after stimulus onset. The total territory engaged by the stimulus ranged
      from 0.5 to 2.9 mm(2) (2-11 barrels). Stimulus site dictated the domain of
      activity. To quantify the coding of whisker location, we applied the population
      d' measure of discriminability. Activity patterns elicited by two whiskers were
      highly discriminable at the initial cortical response; peak discriminability
      typically occurred within 16 msec of stimulus onset. To determine how widely
      information about stimulus location was distributed, we measured population d'
      while excluding response data from the on-center electrodes of the two tested
      whiskers. Response patterns remained discriminable, indicating that information
      about stimulus location was distributed across barrel cortex. Taken together,
      these results show that single-whisker deflections are represented in a
      multicolumn region constrained by barrel cortex map topography. The nature of
      this coding allows information about stimulus location to be coded extremely
      rapidly and unambiguously by one to two spikes per neuron.

PMID- 10934265
TI  - Dissociable neural responses in human reward systems.
AB  - Reward is one of the most important influences shaping behavior. Single-unit
      recording and lesion studies in experimental animals have implicated a number of
      regions in response to reinforcing stimuli, in particular regions of the extended
      limbic system and the ventral striatum. In this experiment, functional
      neuroimaging was used to assess neural response within human reward systems under
      different psychological contexts. Nine healthy volunteers were scanned using
      functional magnetic resonance imaging during the performance of a gambling task
      with financial rewards and penalties. We demonstrated neural sensitivity of
      midbrain and ventral striatal regions to financial rewards and hippocampal
      sensitivity to financial penalties. Furthermore, we show that neural responses in
      globus pallidus, thalamus, and subgenual cingulate were specific to high reward
      levels occurring in the context of increasing reward. Responses to both reward
      level in the context of increasing reward and penalty level in the context of
      increasing penalty were seen in caudate, insula, and ventral prefrontal cortex.
      These results demonstrate dissociable neural responses to rewards and penalties
      that are dependent on the psychological context in which they are experienced.

PMID- 10934264
TI  - Granule-like neurons at the hilar/CA3 border after status epilepticus and their
      synchrony with area CA3 pyramidal cells: functional implications of seizure
      induced neurogenesis.
AB  - A group of neurons with the characteristics of dentate gyrus granule cells was
      found at the hilar/CA3 border several weeks after pilocarpine- or kainic acid
      induced status epilepticus. Intracellular recordings from pilocarpine-treated
      rats showed that these "granule-like" neurons were similar to normal granule
      cells (i. e., those in the granule cell layer) in membrane properties, firing
      behavior, morphology, and their mossy fiber axon. However, in contrast to normal
      granule cells, they were synchronized with spontaneous, rhythmic bursts of area
      CA3 pyramidal cells that survived status epilepticus. Saline-treated controls
      lacked the population of granule-like cells at the hilar/CA3 border and CA3
      bursts. In rats that were injected after status epilepticus with
      bromodeoxyuridine (BrdU) to label newly born cells, and also labeled for
      calbindin D(28K) (because it normally stains granule cells), many double-labeled
      neurons were located at the hilar/CA3 border. Many BrdU-labeled cells at the
      hilar/CA3 border also were double-labeled with a neuronal marker (NeuN). Taken
      together with the recent evidence that granule cells that are born after seizures
      can migrate into the hilus, the results suggest that some newly born granule
      cells migrate as far as the CA3 cell layer, where they become integrated
      abnormally into the CA3 network, yet they retain granule cell intrinsic
      properties. The results provide insight into the physiological properties of
      newly born granule cells in the adult brain and suggest that relatively rigid
      developmental programs set the membrane properties of newly born cells, but
      substantial plasticity is present to influence their place in pre-existing
      circuitry.

PMID- 10934266
TI  - Relationship among discharges of neighboring neurons in the rat prefrontal cortex
      during spatial working memory tasks.
AB  - The relationship among discharges of neurons that were recorded simultaneously
      with tetrodes in the rat medial prefrontal cortex was analyzed. Spatial working
      memory tasks were divided into several distinct stages based on the behavioral
      correlates of individual neurons, and interneuronal correlation of signal (mean
      discharge rate at each stage) and noise (trial-to-trial deviation from the
      signal) was calculated. Behavioral correlates of neighboring neurons were quite
      heterogeneous and, accordingly, average signal correlation was relatively low (
      approximately 0.16). Noise correlation was even lower ( approximately 0.06), but
      neuronal noise was more correlated among the neurons with similar signals. Spikes
      underlying the signal and noise correlation among the prefrontal cortical neurons
      were loosely synchronized over a few hundred milliseconds. These results suggest
      that neighboring prefrontal cortical neurons process largely independent
      information and have weakly correlated noise and that precisely synchronized
      spikes play a relatively minor role in producing the correlated signal and noise
      among these neurons.

PMID- 10934267
TI  - Prefrontal-temporal circuitry for episodic encoding and subsequent memory.
AB  - Humans encounter and form memories for multiple types of experiences that differ
      in content, novelty, and memorability. Critical for understanding memory is
      determining (1) how the brain supports the encoding of events with differing
      content and (2) whether neural regions that are sensitive to novelty also
      influence whether stimuli will be subsequently remembered. This event-related
      functional magnetic resonance imaging (fMRI) study crossed content
      (picture/word), novelty (novel/repeated), and subsequent memory
      (remembered/forgotten) to examine prefrontal and temporal lobe contributions to
      encoding. Results revealed three patterns of encoding-related activation in
      anatomically connected inferior prefrontal and lateral temporal structures that
      appeared to vary depending on whether visuospatial/visuo-object,
      phonological/lexical, or semantic attributes were processed. Event content also
      modulated medial temporal lobe activity; word encoding predominantly activated
      the left hemisphere, whereas picture encoding activated both hemispheres.
      Critically, in prefrontal and temporal regions that were modulated by novelty,
      the magnitude of encoding activation also predicted whether an event would be
      subsequently remembered. These results suggest that (1) regions that demonstrate
      a sensitivity to novelty may actively support encoding processes that impact
      subsequent explicit memory and (2) multiple content-dependent prefrontal-temporal
      circuits support event encoding. The similarities between prefrontal and lateral
      temporal encoding responses raise the possibility that prefrontal modulation of
      posterior cortical representations is central to encoding.

PMID- 10934269
TI  - Impact of correlated synaptic input on output firing rate and variability in
      simple neuronal models.
AB  - Cortical neurons are typically driven by thousands of synaptic inputs. The
      arrival of a spike from one input may or may not be correlated with the arrival
      of other spikes from different inputs. How does this interdependence alter the
      probability that the postsynaptic neuron will fire? We constructed a simple
      random walk model in which the membrane potential of a target neuron fluctuates
      stochastically, driven by excitatory and inhibitory spikes arriving at random
      times. An analytic expression was derived for the mean output firing rate as a
      function of the firing rates and pairwise correlations of the inputs. This
      stochastic model made three quantitative predictions. (1) Correlations between
      pairs of excitatory or inhibitory inputs increase the fluctuations in synaptic
      drive, whereas correlations between excitatory-inhibitory pairs decrease them.
      (2) When excitation and inhibition are fully balanced (the mean net synaptic
      drive is zero), firing is caused by the fluctuations only. (3) In the balanced
      case, firing is irregular. These theoretical predictions were in excellent
      agreement with simulations of an integrate-and-fire neuron that included multiple
      conductances and received hundreds of synaptic inputs. The results show that, in
      the balanced regime, weak correlations caused by signals shared among inputs may
      have a multiplicative effect on the input-output rate curve of a postsynaptic
      neuron, i.e. they may regulate its gain; in the unbalanced regime, correlations
      may increase firing probability mainly around threshold, when output rate is low;
      and in all cases correlations are expected to increase the variability of the
      output spike train.

PMID- 10934268
TI  - Postsynaptic variability of firing in rat cortical neurons: the roles of input
      synchronization and synaptic NMDA receptor conductance.
AB  - Neurons in the functioning cortex fire erratically, with highly variable
      intervals between spikes. How much irregularity comes from the process of
      postsynaptic integration and how much from fluctuations in synaptic input? We
      have addressed these questions by recording the firing of neurons in slices of
      rat visual cortex in which synaptic receptors are blocked pharmacologically,
      while injecting controlled trains of unitary conductance transients, to
      electrically mimic natural synaptic input. Stimulation with a Poisson train of
      fast excitatory (AMPA-type) conductance transients, to simulate independent
      inputs, produced much less variability than encountered in vivo. Addition of NMDA
      type conductance to each unitary event regularized the firing but lowered the
      precision and reliability of spikes in repeated responses. Independent Poisson
      trains of GABA-type conductance transients (reversing at the resting potential),
      which simulated independent activity in a population of presynaptic inhibitory
      neurons, failed to increase timing variability substantially but increased the
      precision of responses. However, introduction of synchrony, or correlations, in
      the excitatory input, according to a nonstationary Poisson model, dramatically
      raised timing variability to in vivo levels. The NMDA phase of compound AMPA-NMDA
      events conferred a time-dependent postsynaptic variability, whereby the
      reliability and precision of spikes degraded rapidly over the 100 msec after the
      start of a synchronous input burst. We conclude that postsynaptic mechanisms add
      significant variability to cortical responses but that substantial synchrony of
      inputs is necessary to explain in vivo variability. We suggest that NMDA
      receptors help to implement a switch from precise firing to random firing during
      responses to concerted inputs.

PMID- 10934270
TI  - NAC-1 is a brain POZ/BTB protein that can prevent cocaine-induced sensitization
      in the rat.
AB  - Levels of the mRNA NAC-1 are increased in the rat forebrain weeks after cocaine
      exposure. This long-term neuroadaptation occurs during the expression of
      behavioral sensitization, a model of psychostimulant-induced paranoia. NAC-1, the
      protein encoded by this cocaine-regulated mRNA, contains a Pox virus and zinc
      finger/bric-a-brac tramtrack broad complex (POZ/BTB) motif, which mediates
      interactions among several transcriptional regulators. The present studies
      demonstrate that NAC-1 acts as a transcription factor. NAC-1 was localized to the
      nucleus of neurons in the brain. Transfection of NAC-1 in cell culture repressed
      transcription of a reporter gene. NAC-1 was also able to affect the actions of
      other POZ/BTB proteins in mammalian two-hybrid studies; these interactions
      required the presence of the POZ/BTB domain. However, NAC-1 appears to be a
      unique POZ/BTB transcriptional regulator because it does not contain any zinc
      finger regions found in these other DNA-binding proteins. Adenoviral-mediated
      overexpression of NAC-1 protein in the rat nucleus accumbens prevented the
      development but not the expression of behavioral sensitization produced by
      repeated administration of cocaine. Thus, NAC-1 may modify the long-term
      behaviors of psychostimulant abuse by regulating gene transcription in the
      mammalian brain.

PMID- 10934271
TI  - Modulation of absence seizures by the GABA(A) receptor: a critical rolefor
      metabotropic glutamate receptor 4 (mGluR4).
AB  - Experimental absence seizures are associated with perturbations in the
      presynaptic release of GABA and glutamate within thalamocortical circuitry. The
      release of both glutamate and GABA is regulated by group III metabotropic
      glutamate receptors (mGluRs). Therefore, we examined the susceptibility of mice
      lacking the mGluR4 subtype of mGluR (mGluR4(-/-)) versus their wild-type controls
      (mGluR4(+/+)) to absence seizures induced either by gamma-hydroxybutyrate (GHB)
      or the GABA(B) agonist (-) baclofen or by low doses of the GABA(A) receptor
      (GABA(A)R) antagonists pentylenetetrazole, bicuculline, or picrotoxin. There was
      no difference between mGluR4(-/-) and mGluR4(+/+) mice in threshold to absence
      seizures induced by either GHB or (-) baclofen. In contrast, the mGluR4(-/-) mice
      were markedly resistant to absence seizures induced by low doses of GABA(A)R
      antagonists. No differences were observed between mGluR4(-/-) and mGluR4(+/+)
      mice in threshold to clonic or tonic seizures induced by higher doses of GABA(A)R
      antagonists, strychnine, or electroshock, indicating that seizure resistance in
      the mGluR4(-/-) mice was restricted solely to absence seizures. The resistance of
      mGluR4(-/-) mice to absence seizures induced by GABA(A)R antagonists was mimicked
      by bilateral administration of a mGluR4 antagonist into the nucleus reticularis
      thalami (nRT) of mGluR4(+/+) mice. Conversely, intra-nRT administration of a
      mGluR4 agonist in mGluR4(+/+) mice exacerbated GABA(A)R-induced absence seizures.
      These data indicate that the presence of mGluR4 within nRT is critical to
      GABAergic modulation of thalamocortical synchronization in normal and
      pathological states, such as generalized absence epilepsy.

PMID- 10934272
TI  - The role of ventromedial prefrontal cortex in the recovery of extinguished fear.
AB  - Conditioned fear responses to a tone paired with footshock extinguish when the
      tone is presented repeatedly in the absence of shock. Rather than erase the tone
      shock association, extinction is thought to involve new learning accompanied by
      inhibition of conditioned responding. Despite much interest in extinction from a
      clinical perspective, little is known about the neural circuits that are
      involved. Although the prefrontal cortex has a well established role in the
      inhibition of inappropriate behaviors, previous reports have disagreed as to the
      role of the ventromedial prefrontal cortex (vmPFC) in extinction. We have
      reexamined the effects of electrolytic vmPFC lesions made before training on the
      acquisition, extinction, and recovery of conditioned fear responses in a 2 d
      experiment. On Day 1 vmPFC lesions had no effect on acquisition or extinction of
      conditioned freezing and suppression of bar pressing. On Day 2 sham rats
      recovered only 27% of their acquired freezing, whereas vmPFC-lesioned rats
      recovered 86%, which was indistinguishable from a control group that never
      received extinction. The high recovery in lesioned rats could not be attributed
      to decreased motivation or altered sensitivity to footshock. vmPFC lesions that
      spared the caudal infralimbic (IL) nucleus had no effect. Thus, the vmPFC
      (particularly the IL nucleus) is not necessary for expression of extinction, but
      it is necessary for the recall of extinction learning after a long delay. These
      data suggest a role of the vmPFC in consolidation of extinction learning or the
      recall of contexts in which extinction took place.

PMID- 10934273
TI  - Testing the disinhibition hypothesis of epileptogenesis in vivo and during
      spontaneous seizures.
AB  - The "disinhibition" hypothesis contends that (1) seizures begin when granule
      cells in the dentate gyrus of the dorsal hippocampus are disinhibited and (2)
      disinhibition occurs because GABAergic interneurons are excessively inhibited by
      other GABAergic interneurons. We tested the disinhibition hypothesis using the
      experimental model that inspired it-naturally epileptic Mongolian gerbils. To
      determine whether there is an excess of GABAergic interneurons in the dentate
      gyrus of epileptic gerbils, as had been reported previously, GABA
      immunocytochemistry, in situ hybridization of GAD67 mRNA, and the optical
      fractionator method were used. There were no significant differences in the
      numbers of GABAergic interneurons. To determine whether granule cells in
      epileptic gerbils were disinhibited during the interictal period, IPSPs were
      recorded in vivo with hippocampal circuits intact in urethane-anesthetized
      gerbils. The reversal potentials and conductances of IPSPs in granule cells in
      epileptic versus control gerbils were similar. To determine whether the level of
      inhibitory control in the dentate gyrus transiently decreases before seizure
      onset, field potential responses to paired-pulse perforant path stimulation were
      obtained from the dorsal hippocampus while epileptic gerbils experienced
      spontaneous seizures. Evidence of reduced inhibition was found after, but not
      before, seizure onset, indicating that seizures are not triggered by
      disinhibition in this region. However, seizure-induced depression of inhibition
      may amplify and promote the spread of seizure activity to other brain regions.
      These findings do not support the disinhibition hypothesis and suggest that in
      this model of epilepsy seizures initiate by another mechanism or at a different
      site.

PMID- 10934274
TI  - Physiological and anatomical organization of multiwhisker response interactions
      in the barrel cortex of rats.
AB  - To understand the physiological properties and anatomical organization of the
      spatiotemporal interaction of the responses to multiwhisker stimulation in
      neurons of the rat barrel cortex, single-unit recordings of 114 neurons were
      performed across all layers (layer II/III, n = 39; IV, n = 33; V/VI, n = 42) of
      the posteromedial barrel subfield of the primary somatosensory cortex of
      anesthetized rats. Two neighboring principal and adjacent whiskers (PW and AW,
      respectively) in the same row were deflected rostrally or caudally at varying
      interstimulus intervals (ISIs). In 37% of the neurons, the response to the
      combined stimulus was significantly larger than the sum of the responses to
      stimulation of the individual whiskers. In instances in which response
      facilitation was observed, selectivity was noted for the combination (75%) of the
      PW with a particular AW or for a particular direction (60%) of whisker
      deflection. The direction bias of the responses to multiwhisker stimulation was
      well correlated with that of the sum of the responses to single whisker
      stimulation (r = 0.83; p < 0.001). The pattern and magnitude of the response
      interaction in the neurons of the superficial layers were closely related to the
      location of the recorded cell in the barrel columns. Multiwhisker stimulation at
      short ISIs (</=3 msec) evoked prominent response facilitation in cells located
      close to the border between two columns (p < 0.05, one-way ANOVA), where two
      excitatory inputs were expected to arrive at the same time. Our results suggest
      that the spatiotemporal patterns of multiwhisker stimulation, such as whisker
      combination, direction of deflection, and timing, are expressed as different
      magnitudes of response interaction, which depends on the proximity of cells to
      home and adjacent barrel columns.

PMID- 10934275
TI  - Transduction sites of vagal mechanoreceptors in the guinea pig esophagus.
AB  - Extrinsic afferent neurons play an essential role in both sensation and reflex
      control of visceral organs, but their specialized morphological peripheral
      endings have never been functionally identified. Extracellular recordings were
      made from fine nerve trunks running between the vagus nerve and esophagus of the
      guinea pig. Mechanoreceptors, which responded to esophageal distension, fired
      spontaneously, had low thresholds to circumferential stretch, and were slowly
      adapting. Calibrated von Frey hairs (0.12 mN) were used to probe the serosal
      surface at 100-200 sites, which were mapped on a video image of the live
      preparation. Each stretch-sensitive unit had one to three highly localized
      receptive fields ("hot spots"), which were marked with Indian ink applied on the
      tip of the von Frey hair. Recorded nerve trunks were then filled anterogradely,
      using biotinamide in an artificial intracellular solution. Receptive fields were
      consistently associated with intraganglionic laminar endings (IGLEs) in myenteric
      ganglia, but not with other filled neuronal structures. The average distance of
      receptive fields to IGLEs was 73 +/- 14 microm (24 receptive fields, from 12
      units; n = 5), compared to 374 +/- 17 microm for 240 randomly generated sites (n
      = 5; p < 0.001). After maintained probing on a single receptive field,
      spontaneous discharge of units was inhibited, as were responses to distension.
      During adapted discharge to maintained distension, interspike intervals were
      distributed in a narrow range. This indicates that multiple receptive fields
      interact to encode mechanical distortion in a graded manner. IGLEs are
      specialized transduction sites of mechanosensitive vagal afferent neurons in the
      guinea pig esophagus.

PMID- 10934276
TI  - Performance of fly visual interneurons during object fixation.
AB  - Neurons involved in the processing of optic flow are usually analyzed using
      stimuli designed by the experimenter. However, in real life optic flow depends on
      locomotive behavior. We characterized the performance of motion-sensitive neurons
      in the visual system of the fly using optic flow as occurring in behavioral
      situations during object fixation. Optic flow generated by tethered flying flies
      in a flight simulator was subsequently replayed while recording the responses of
      two cell types in the fly's motion pathway presumably involved in the detection
      of objects and of deviations from a straight flight course, respectively. FD1b
      cells, which are representatives of the so-called figure-detection cells,
      responded very specifically to object motion. Although object selectivity of
      these cells is attributable to inhibition during large-field motion, the
      influence of background motion during object fixation was almost negligible. In
      contrast, the cells of the so-called horizontal system (HS cells) are most
      sensitive to background motion, as elicited during deviations of the animal from
      its course. During object fixation, the responses of HS cells depended on both
      object and background motion. The simulated distance of the background to the fly
      did not have a strong influence on the responses of either cell type. The
      specificity for detecting deviations from a straight course is enhanced by
      subtraction of the signals of HS cells in both halves of the brain. In contrast,
      the FD1b cells in the two halves of the brain need to interact in a nonlinear way
      to ensure efficient detection of objects.

PMID- 10934278
TI  - Modulation of hippocampal excitability and seizures by galanin.
AB  - Previous studies have shown that the expression of the neuropeptide galanin in
      the hippocampus is altered by seizures and that exogenous administration of
      galanin into the hippocampus attenuates seizure severity. To address the role of
      endogenous galanin in modulation of hippocampal excitability and its possible
      role in seizure mechanisms, we studied two types of transgenic mice: mice with a
      targeted disruption of the galanin gene (GalKO) and mice that overexpress the
      galanin gene under a dopamine-beta-hydroxylase promoter (GalOE). GalKO mice
      showed increased propensity to develop status epilepticus after perforant path
      stimulation or systemic kainic acid, as well as greater severity of
      pentylenetetrazol-induced convulsions. By contrast, GalOE mice had increased
      resistance to seizure induction in all three models. Physiological tests of
      hippocampal excitability revealed enhanced perforant path-dentate gyrus long-term
      potentiation (LTP) in GalKO and reduced LTP in GalOE. GalKO showed increased
      duration of afterdischarge (AD) evoked from the dentate gyrus by perforant path
      simulation, whereas GalOE had increased threshold for AD induction.
      Depolarization-induced glutamate release from hippocampal slices was greater in
      GalKO and lower in GalOE, suggesting that alterations of physiological and
      seizure responses in galanin transgenic animals may be mediated through
      modulation of glutamate release. Our data provide further evidence that
      hippocampal galanin acts as an endogenous anticonvulsant and suggest that
      genetically induced changes in galanin expression modulate both hippocampal
      excitability and predisposition to epileptic seizures.

PMID- 10934277
TI  - AMPA receptor-mediated, calcium-dependent CREB phosphorylation in a subpopulation
      of auditory neurons surviving activity deprivation.
AB  - Although dependence on afferent synaptic activity has been shown for central
      neurons in every sensory system, the mechanisms of afferent maintenance of target
      sensory neurons are not understood. Neurons in the cochlear nucleus (CN) require
      afferent activity for maintenance and survival. One of the earliest changes seen
      after activity deprivation is an increase in intracellular calcium that leads to
      the death of 30% of the neuronal population. Sixty minutes after deafferentation,
      the surviving neurons show increased phosphorylation of the transcription factor
      calcium/cAMP response element-binding protein (CREB). CREB phosphorylation in
      activity-deprived CN neurons is dependent on increased intracellular calcium
      resulting from influx through AMPA receptors and is mediated by
      calcium/calmodulin-dependent kinases and protein kinase A. We conclude that in CN
      neurons, the deafferentation-induced increase in calcium activates at least two
      kinase pathways that phosphorylate CREB in surviving neurons. We hypothesize that
      this phosphorylation results in the transcription of genes containing the
      calcium/cAMP response element within their promoter regions, and these genes code
      for proteins that allow the neurons to compensate for their hypercalcemic,
      activity-deprived state.

PMID- 10934279
TI  - NMDA, but not dopamine D(2), receptors in the rat nucleus accumbens areinvolved
      in guidance of instrumental behavior by stimuli predicting reward magnitude.
AB  - Expectancy of future reward is an important factor guiding the speed of
      instrumental behavior. The present study sought to explore whether signals
      transmitted via the NMDA subtype of glutamate receptors and via dopamine D(2)
      receptors in the nucleus accumbens (NAc) are critical for the determination of
      reaction times (RTs) of instrumental responses by the expectancy of future
      reward. A simple RT task for rats demanding conditioned lever release was used in
      which the upcoming reward magnitude (5 or 1 pellet) was signaled in advance by
      discriminative stimuli. In trained rats, RTs of conditioned responses with
      expectancy of a high reward magnitude were found to be significantly shorter. The
      shortening of RTs by stimuli predictive of high reward to be obtained was dose
      dependently impaired by bilateral intra-NAc infusion of the competitive NMDA
      antagonist dl-2-amino-5-phosphonovaleric acid (APV) (1, 2, or 10 microg in 0.5
      microl/side), but not by infusion of the preferential dopamine D(2) antagonist
      haloperidol (5 and 12.5 microg in 0.5 microl/side) or by infusion of vehicle (0.5
      microl/side). In conclusion, the data reveal that in well trained animals
      stimulation of intra-NAc NMDA, but not of dopamine D(2), receptors, is critically
      involved in guiding the speed of instrumental responses according to stimuli
      predictive of the upcoming reward magnitude.

PMID- 10934280
TI  - Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1
      beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on
      heat-evoked calcitonin gene-related peptide release from rat skin.
AB  - Proinflammatory cytokines contribute to the development of inflammatory and
      neuropathic pain and hyperalgesia in many in vivo models. The rat skin model was
      used to investigate the effects of proinflammatory cytokines on the basal and
      heat-evoked release of calcitonin gene-related peptide from nociceptors in vitro.
      In contrast to the excitatory effects of cytokines observed in vivo, none of the
      cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at
      normal skin temperature of 32 degrees C. However, the cytokines IL-1beta, tumor
      necrosis factor (TNF)-alpha, and IL-6 but not IL-8 induced a pronounced and
      transient sensitization of the heat-evoked CGRP release from nociceptors in
      vitro. This heat sensitization was dose dependent, with EC(50) for IL-1 beta of
      2.7 ng/ml and for TNF-alpha of 3.1 ng/ml. The maximum IL-1 beta effect reached
      almost 600% of the heat-evoked release, and the maximum TNF-alpha effect induced
      a rise in CGRP release of 350%. In contrast to IL-1 beta and TNF-alpha, IL-6 did
      not induce heat sensitization when applied alone but was only effective in the
      presence of soluble IL-6 receptor. This suggests a constitutive expression of
      signaling receptors for TNF and IL-1 beta and the signal transduction molecule
      gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine
      signaling observed in the present study was independent of transcriptional
      pathways because sensitization occurred on short latency in vitro and under
      conditions that excluded chemotactic accumulation of immune cells from blood
      vessels. Our results demonstrate that interleukins may play an important role in
      the initiation of heat hyperalgesia in inflammation and neuropathy.

PMID- 10934281
TI  - Nitric oxide-stimulated increase in extracellular adenosine accumulation in rat
      forebrain neurons in culture is associated with ATP hydrolysis and inhibition of
      adenosine kinase activity.
AB  - Adenosine is a putative endogenous sleep-inducing substance, and nitric oxide has
      been implicated in arousal and sleep mechanisms. We found that various nitric
      oxide donors, including diethylamine NONOate (DEA/NO), stimulated large increases
      in extracellular adenosine in nearly pure cultures of forebrain neurons. The
      effect of DEA/NO could be blocked by 2-phenyl-4,4,5, 5-tetramethyl-imidazoline-1
      oxyl-oxide and could not be mimicked by degraded solutions of DEA/NO or by DEA
      itself; therefore, it was caused by nitric oxide release on hydrolysis of the
      parent compound. The accumulation of adenosine was not blocked by probenecid or
      GMP, suggesting that neither extracellular cAMP nor extracellular AMP was the
      source, and that adenosine was therefore the most likely species transported
      across the plasma membrane. To pursue this further, we tested the effect of
      DEA/NO on cellular ATP and found a significant fall in ATP associated with
      exposure to nitric oxide. In addition, exposure to DEA/NO nearly completely
      inhibited adenosine kinase activity. It has been found previously that adenosine
      kinase is inhibited by its substrate, adenosine. We found that exposure to nitric
      oxide increased intracellular adenosine to 125 +/- 18% of control values (p <
      0.01), consistent with the possibility that in our system the inhibition of
      adenosine kinase is related to an increase in intracellular adenosine, and that
      the effect of nitric oxide on extracellular adenosine is significantly
      potentiated by substrate inhibition of adenosine kinase. Furthermore, nitric
      oxide-stimulated adenosine accumulation may be important in the regulation of
      behavioral state.

PMID- 10934282
TI  - Mechanisms for ovariectomy-induced hyperalgesia and its relief by calcitonin:
      participation of 5-HT1A-like receptor on C-afferent terminals in substantia
      gelatinosa of the rat spinal cord.
AB  - Chronic treatment with calcitonin in osteoporotic patients alleviates the pain
      associated with this condition by an unknown mechanism. In ovariectomized rats
      that develop osteoporosis and hyperalgesia, we examined whether a functional
      change in serotonergic systems in the spinal dorsal horn was involved, using
      whole-cell recordings from substantia gelatinosa neurons in spinal cord slices
      and [(3)H]8-hydroxy-2(di-n-propylamino)tetralin ([(3)H]8-OH-DPAT) binding.
      Hyperalgesia could be attributed to the elimination of presynaptic inhibition by
      5-HT of glutamatergic primary C-afferent terminals and an associated decrease in
      the density of [(3)H]8-OH-DPAT binding sites whose receptors are neither 5-HT(1A)
      nor 5-HT(7)-subtype. These changes in serotonergic systems were restored after
      chronic treatment with calcitonin. Reversal of 5-HT receptor changes by
      calcitonin treatment may provide an explanation for its analgesic actions in
      patients.

PMID- 10934283
TI  - Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity
      in the rat brain: role of microglia.
AB  - Inflammation in the brain has been increasingly associated with the development
      of a number of neurological diseases. The hallmark of neuroinflammation is the
      activation of microglia, the resident brain immune cells. Injection of bacterial
      endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia
      nigra of adult rats produced neurodegeneration only in the substantia nigra.
      Although LPS appeared to impact upon mesencephalic neurons in general, an
      extensive loss of dopaminergic neurons was observed. Analysis of the abundance of
      microglia revealed that the substantia nigra had the highest density of
      microglia. When mixed neuron-glia cultures derived from the rat hippocampus,
      cortex, or mesencephalon were treated with LPS, mesencephalic cultures became
      sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose
      dependent manner with the production of inflammatory factors and a loss of
      dopaminergic and other neurons. In contrast, hippocampal or cortical cultures
      remained insensitive to LPS treatment at concentrations as high as 10 microg/ml.
      Consistent with in vivo observations, mesencephalic cultures had fourfold to
      eightfold more microglia than cultures from other regions. The positive
      correlation between abundance of microglia and sensitivity to LPS-induced
      neurotoxicity was further supported by the observation that supplementation with
      enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive
      cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data
      indicate that the region-specific differential susceptibility of neurons to LPS
      is attributable to differences in the number of microglia present within the
      system and may reflect levels of inflammation-related factors produced by these
      cells.

PMID- 10934284
TI  - Molecular aspects of polycythemia vera (review).
AB  - Polycythemia vera (PV) is a rare, progressive myeloproliferative disorder thought
      to originate from the clonal expansion of a multipotent haemopoietic stem cell.
      This disease is characterised by hyperproliferation of the erythroid, myeloid and
      megakaryocyte lineages in the early phase, anaemia and fibrosis in the spent
      phase, and with a significant number of patients developing acute myeloid
      leukaemia (AML) in the final phase. Studies investigating the growth factor
      requirements of committed progenitors have shown hypersensitivity to a number of
      haemopoietic growth factors (HGF) in vitro and several HGF receptor and
      signalling molecule alterations have been reported. The findings to date,
      however, are unable to account for the transformation of a primitive stem cell
      and the many alterations to growth factor responses seen in PV progenitors.
      Identification of the primary lesion that leads to the pathogenesis of PV is of
      major importance given the profound effects on regulation of the haemopoietic
      stem cell compartment. In this article we focus on characteristics of the
      disease, research findings to date and possible mechanisms to explain altered
      growth factor responses, receptor alterations and signalling abnormalities in PV.

PMID- 10934285
TI  - Regulation of apolipoprotein E production in macrophages (review).
AB  - Apolipoprotein E (apo E), a 34 kDa component of lipoproteins produced by the
      liver and in circulating macrophages, plays a critical role in the reverse
      transport of cholesterol to the liver via the circulation. Cholesterol-rich
      macrophages (macrophage foam cells) are a major cell type in human
      atherosclerotic lesions. Apo E deficiency in mice leads to the formation of
      atherosclerotic lesions. Conversely, macrophage-specific expression of apo E in
      these deficient mice can reduce the extent of atherosclerosis. These
      observations, together with the anti-inflammatory and anti-proliferative
      properties of Apo E, demonstrate an atheroprotective role for the apolipoprotein.
      Agents that regulate macrophage metabolism are also able to modulate apo E
      expression. Sterol loading, for example, enhances apo E synthesis and secretion.
      Additionally, exposure of macrophage foam cells to cholesterol acceptors such as
      apo A-1, the protein component of high density lipoprotein, further enhance apo E
      secretion. Cytokines can have a negative regulatory effect on apo E production in
      macrophages. Apo E expression is controlled at the transcriptional, post
      transcriptional and post-translational level. Here, we review the cellular and
      molecular mechanisms modulating apo E synthesis and secretion in macrophages.

PMID- 10934286
TI  - Chaperone-mediated cross-priming: a hitchhiker's guide to vesicle transport
      (review).
AB  - The resident endoplasmic reticulum (ER) chaperone proteins GRP94 (gp96) and
      calreticulin can activate the immune system to slow or stop the progression of
      tumors by escorting tumor-derived peptides into the endogenous antigen
      presentation pathway of antigen presenting cells (APC). Although the
      phenomenology of cross-priming is well worked out, the mechanism(s) remains
      unclear. Continuing insights into cellular protein trafficking pathways suggest
      several means by which chaperones could travel from the extracellular space into
      the endosome, lysosome or ER of APC. In particular, proteins that cycle between
      two or more compartments and those that undergo and mediate retrograde flow offer
      models of how exogenous chaperones might travel in the APC. New insights into how
      non-chaperone proteins access the APC antigen presentation pathway also suggest
      several ways this process could occur.

PMID- 10934287
TI  - Mutational analysis of HIV-1 gag proteins (review).
AB  - The mature Gag proteins of human immunodeficiency virus type 1 (HIV-1) are major
      components of infectious virions, and thought to carry out numerous functions
      throughout the HIV-1 replication cycle. We have recently generated numerous gag
      gene mutants of HIV-1 to genetically study the functions of the Gag proteins.
      Through the biological and biochemical analyses, our HIV-1 gag mutants have been
      grouped into early (defective for uncoating/reverse transcription), late
      (defective for virion release/maturation), and early/late (defective for both
      steps) mutants. Many mutants are found to efficiently inhibit the replication of
      wild-type virus. Worthy of note, there are some early mutants which show host
      cell-dependent replication potential.

PMID- 10934288
TI  - Suppression of the tissue factor-dependent coagulation cascade: a contributing
      factor for the development of intratumoral hemorrhage in glioblastoma.
AB  - To clarify factors that may contribute to the development of intratumoral
      hemorrhage, we analyzed the expression of tissue factor (TF), an initiator of the
      extrinsic coagulation pathway, and of tissue factor pathway inhibitor (TFPI) in
      glioblastomas with or without massive intratumoral hematoma. Among 196 glioma
      cases reviewed, there were 13 with macroscopic intratumoral hemorrhage. We
      focused on the glioblastomas and used immunoblot- and immunohistochemical methods
      to compare the expression of TF and TFPI in 9 glioblastomas with macroscopic
      hematoma and 30 glioblastomas without macroscopic hemorrhage. Although TF was
      expressed in most glioblastomas irrespective of the presence or absence of
      macroscopic hemorrhage, the staining patterns differed significantly: TF-positive
      glioma cells were diffusely present in the non-hemorrhage group; in the group
      with hemorrhage, positive cells, primarily macrophages, were scattered throughout
      the tissue examined. The expression of TFPI was significantly higher in the group
      with than in the group without hemorrhage. Our results suggest that local
      suppression of the TF-dependent coagulation cascade is a contributing factor that
      permits the occurrence of intratumoral hemorrhage.

PMID- 10934289
TI  - Pheophorbide a, a moiety of chlorophyll a, induces apoptosis in human lymphoid
      leukemia molt 4B cells.
AB  - The exposure of human lymphoid leukemia Molt 4B cells to pheophorbide a (PPB a),
      a moiety of chlorophyll a, led both to growth inhibition and induction of
      programmed cell death (apoptosis). The growth inhibition by PPB a was much
      stronger than that by chlorophyll a. Morphological change showing apoptotic
      bodies was observed in the Molt 4B cells treated with PPB a. The fragmentation by
      PPB a of DNA to oligonucleosomal-sized fragments, that are characteristics of
      apoptosis, was observed to be concentration- and time-dependent. These findings
      suggest that growth inhibition by PPB a of Molt 4B cells results from the
      induction of apoptosis and that PPB a, moiety of chlorophyll a, is essential for
      exertion of antitumor and apoptosis-inducing activity in these cells.

PMID- 10934290
TI  - Genetic variations of the midkine (MK) gene in human sporadic colorectal and
      gastric cancers.
AB  - Midkine (MK), a retinoic acid responsible protein, is regulated during
      development and may play an important role in tumorigenesis. A search for genetic
      variations of the MK gene, located on chromosome 11q11.2 in humans, has not yet
      been conducted in cancers. To examine the entire coding region, as well as 4
      regions of the promoter covering all functional motifs, 8 sets of intron-based
      and promoter region primers were designed. Using these primers, polymerase chain
      reaction-single strand conformation polymorphism (PCR-SSCP) analysis of genomic
      DNA samples from 60 sporadic colorectal and 37 sporadic gastric cancer patients
      was carried out. This analysis, followed by DNA sequencing, revealed a
      heterozygous g/t polymorphism at the 62nd base on intron 3 in five colorectal
      tumors (8.3%) and one gastric tumor (2.7%). In the promoter region, a
      heterozygous CTT deletion, creating a (CTTTT)2 repeat, in one colorectal cancer
      sample (1.67%) and a heterozygous 2-bp deletion in the G7 tract in another
      colorectal cancer patient were detected. A/G and A/A alleles were also detected
      at nt. -1741 in 36 (97.3%) and one (2.7%) gastric cancer samples, respectively.
      The A/G alleles were observed in all colorectal cancer patients (100%). All
      variations observed in the promoter region showed polymorphism. These results
      suggest that in sporadic colorectal and gastric cancers some gene alterations are
      present in the MK promoter region, but alterations in the coding region are rare.

PMID- 10934291
TI  - Differential transcriptional regulation of silencer of death domains in cord
      blood and peripheral blood lymphocytes.
AB  - We have shown that neonatal lymphocytes are deficient in TNF-induced apoptosis.
      Recently, a 60 kDa protein termed silencer of death domains (SODD) has been shown
      to prevent spontaneous apoptosis. The binding of SODD to DD of the TNFR-I
      maintains DD in monomeric form and prevents their aggregation which is required
      for the apoptotic signal. We examined the expression of SODD mRNA during TNF
      induced apoptosis. Although in non-stimulated cord blood lymphocytes the
      constitutive expression of SODD mRNA was lower than that of non-stimulated
      peripheral blood lymphocytes, following anti-CD3 stimulation SODD mRNA was
      significantly increased in cord blood lymphocytes at 12 and 24 h, returning to
      the baseline at 48 h. In contrast, a modest decrease in SODD transcript was
      observed in peripheral blood lymphocytes. Furthermore, TNF downregulated SODD
      mRNA expression in peripheral blood lymphocytes, whereas it had no significant
      effect on SODD transcripts in cord blood lymphocytes. Therefore, differential
      regulation of SODD may be one of the mechanisms responsible for decreased TNF
      induced apoptosis in neonatal lymphocytes.

PMID- 10934292
TI  - Suppressive effect of endogenous regucalcin on the enhancement of protein
      synthesis and aminoacyl-tRNA synthetase activity in regenerating rat liver.
AB  - The effect of regucalcin, which is a regulatory protein in Ca2+ signaling, on
      protein synthesis in regenerating rat liver was investigated. Protein synthesis
      was assayed in a reaction mixture containing the 5500 g supernatant fraction in
      the presence of [3H]leucine. The presence of anti-regucalcin monoclonal antibody
      (100 and 150 ng/ml) in the reaction mixture caused a significant elevation of in
      vitro protein synthesis. This elevation was completely prevented by the addition
      of regucalcin (1.0 microM). Regenerating liver after partial hepatectomy (HPX)
      induced a significant increase in protein synthesis. This increase was
      significantly enhanced by the presence of anti-regucalcin monoclonal antibody
      (100 ng/ ml). This enhancement was remarkable at 24 and 48 h after HPX.
      [3H]Leucyl-tRNA synthetase activity in the 105000 g supernatant fraction
      (cytosol) of the liver homogenate from normal rats was significantly raised by
      the presence of antibody (100 and 150 ng/ml) in the enzyme reaction mixture.
      Regenerating liver caused a significant elevation of the enzyme activity at 24,
      48, and 72 h after HPX. This elevating was significantly enhanced in the presence
      of antibody (100 ng/ml). The present study suggests that endogenous regucalcin
      has a suppressive effect on the enhancement of protein synthesis in regenerating
      rat liver with a proliferative cells.

PMID- 10934293
TI  - Tissue urokinase-type plasminogen activator receptor levels in breast cancer.
AB  - Cancer invasion is induced by several proteolytic enzyme systems associated with
      the destruction of basement membrane and extracellular matrix. Urokinase-type
      plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1) have
      been reported as prognostic factors in breast cancer patients and plasminogen
      activation is regulated by various factors such as uPAR and growth factors. Thus,
      we examined the tissue levels of urokinase-type plasminogen activator receptor
      (uPAR) in breast cancer patients. Tissue uPAR levels were measured by ELISA assay
      in 268 breast cancer patients. The median and mean values of tissue uPAR level in
      breast cancer were 3.5 ng/mg cytosol protein and 4.8+/-3.6 ng/mg cytosol protein,
      respectively. Tissue uPAR level was the highest in T1 stage, but there was no
      statistical significance between the T stages (p>0.05), nor in nodal stage, in
      the value of uPAR according to progression. And the value of uPAR expression was
      not associated with estrogen and progesterone receptor status, number of involved
      node and percent of node involvement. In TNM stage, tissue uPAR levels were
      higher in patients with stage I-II than in patients with stage III-IV (p=0.027).
      In univariate analysis, nodal factor (p=0.002) and TNM stage (p=0.0004) were
      significant. But, multivariate analysis showed that TNM stage was the only
      significant prognostic factor (p=0.0002). These results suggest that uPAR is
      mainly associated with initial tumor invasion and other factors might be involved
      in later stages of cancer progression.

PMID- 10934294
TI  - Serum HDL cholesterol concentration in patients with squamous cell and small cell
      lung cancer.
AB  - Cancer patients often present altered serum lipid profile including changes of
      HDL cholesterol level. The aim of our work was to evaluate serum level of HDL
      cholesterol in patients with squamous cell and small cell lung cancer and its
      dependence on histological type and clinical stage of lung cancer. Fasting serum
      level of HDL cholesterol was analysed in 135 patients with newly diagnosed lung
      cancer and compared to a control group of healthy men. All lung cancer patients,
      as well as subgroups of squamous cell and small cell lung cancer had
      statistically significantly lower HDL cholesterol concentration than controls.
      There were no statistically significant differences of HDL cholesterol level
      between the histological types or between clinical stages of each histological
      type of lung cancer.

PMID- 10934296
TI  - Expression of the inducible form of the nitric oxide synthase gene in the livers
      of mice with chronic hepatitis.
AB  - The interferon-gamma (IFN-gamma) transgenic mouse expresses the exogenous IFN
      gamma gene in the liver and develops chronic hepatitis. For the present
      experiment, four IFN-gamma transgene (+) mice of 48 weeks of age and 16 IFN-gamma
      transgene (+) mice of 8 weeks of age were used. The four IFN-gamma transgene (+)
      mice of 48 weeks of age showed significantly elevated plasma alanine
      aminotransferase (ALT) and expressed the inducible form of nitric oxide synthase
      (iNOS) mRNA in the liver. Of the 16 IFN-gamma transgene (+) mice of 8 weeks of
      age, iNOS mRNA was expressed in the livers of three. These three mice exhibited
      higher plasma ALT levels than the other mice of 8 weeks of age. The present
      results suggest that iNOS mRNA expression in the liver might be correlated with
      the progression of hepatitis.

PMID- 10934295
TI  - Functional integrity of dispersed islet cells attached to a two-dimensional
      microsupport.
AB  - Dispersed rat pancreatic islet cells were cultured overnight in the presence of
      polystyrene two-dimensional microsupports. About 1.7-1.9x10(6) cells attached to
      the microsupports (832 cm2) were found to display both an insulin content and
      secretory response to D-glucose and/or theophylline comparable to those otherwise
      found in cultured free islet cells. It is proposed that advantage could be taken
      of this approach to study the function of islet cells attached in a standardized
      number to such two-dimensional microsupports.

PMID- 10934297
TI  - Prolongation of the insulinotropic action of glucagon-like peptide 1 by the
      dimethyl ester of succinic acid in an animal model of type-2 diabetes.
AB  - Adult rats, that had been injected with streptozotocin during the neonatal
      period, received a primed constant infusion of succinic acid dimethyl ester (SAD;
      0.5 micromol followed by 0.25 micromol x min(-1), both per g body wt.) in saline
      for 15 min and, at the 5th min of such an infusion, an intravenous injection of
      GLP-1 (5 pmol per g body wt.). Within 2 min, the ester increased the plasma
      insulin concentration by 0.33+/-0.05 nM. Likewise, within 2 min, GLP-1 provoked a
      marked increase in plasma insulin concentration; such an increase was comparable
      in rats infused with either saline or SAD, with an overall mean value of 0.93+/
      0.07 nM. In the rats infused with SAD, however, the secretory response to GLP-1
      appeared more sustained than in the saline-infused animals. For instance, the
      paired ratio for the insulinogenic index at 10/2 min after GLP-1 injection
      averaged 30.5+/-4.0% in SAD-infused rats, as compared (P<0.025) to only 17.0+/
      2.5% in saline-infused animals. These findings suggest that succinic acid esters
      could be used to prolong the insulinotropic action of GLP-1 in the treatment of
      type-2 diabetes.

PMID- 10934298
TI  - Enhancement of protein tyrosine phosphatase activity in the proliferation of
      cloned rat hepatoma H4-II-E cells: suppressive role of endogenous regucalcin.
AB  - The role of endogenous regucalcin in the regulation of protein tyrosine
      phosphatase activity in the proliferation of the cloned rat H4-II-E hepatoma
      cells was investigated. Cells were cultured for 6 to 96 h in a medium containing
      1.0 or 10% fetal bovine serum (FBS). Cell numbers were significantly raised by
      culture with 10% FBS in comparison with that of 1.0% FBS. Protein tyrosine
      phosphatase activity in the cells was significantly elevated by culture with 10%
      FBS for 24 to 96 h as compared with that of 1% FBS. Such an increase was not seen
      in protein phosphatase activity toward phosphoserine or phosphothreonine. The
      presence of anti-regucalcin monoclonal antibody (50 or 100 ng/ml) in the enzyme
      reaction mixture caused a remarkable elevation of protein tyrosine phosphatase
      activity in the cells obtained by culture with 1.0 or 10% FBS. This elevation was
      completely prevented by the addition of regucalcin (10-6 M). The effect of
      antibody in elevating protein tyrosine phosphatase activity in the cells was
      significantly inhibited by the addition of okadaic acid (10-6 M) or vanadate (10(
      6) M), an inhibitor of protein phosphatase, in the reaction mixture. The present
      study suggests that protein tyrosine phosphatase activity in the cloned rat
      hepatoma cells is increased in serum-stimulated cell proliferation, and that
      endogenous regucalcin has a suppressive role in the enhancement of the enzyme
      activity in proliferative cells.

PMID- 10934301
TI  - Changing of the guard.

PMID- 10934299
TI  - Opioid analgesic-induced apoptosis and caspase-independent cell death in human
      lung carcinoma A549 cells.
AB  - We characterized anticancer effects of opioid analgesics that are clinically used
      for cancer patients for pain relief. Treatment with 100 microM buprenorphine, a
      representative analgesic, induced cell death of human carcinomas, such as A549
      (squamous epithelial cell of lung cancer), MCF-7 (breast cancer) and N417 (small
      cell of lung cancer), but not in KATO III (gastric cancer) cells as evaluated by
      alamar blue assay. Among 18 clinically utilized and related analgesics,
      buprenorphine and loperamide showed potent inhibition of cell viability. However,
      these anti-cancer effects were not affected by opioid receptor antagonists nor by
      pertussis toxin. Buprenorphine-induced cell death occurred as early as 1 h after
      the addition, and its T1/2 of cell viability inhibition was 3 h. The cell death
      manifested the characteristics of apoptosis, such as DNA-laddering and nuclear
      fragmentation, which were sensitive to a caspase inhibitor, Z-Asp-CH2-DCB. The
      nuclear fragmentation was independent of cell cycle phase specificity. The
      activity of caspase-3-like protease which is known to be closely related to
      apoptotic DNA laddering was markedly enhanced by buprenorphine. However, the
      inhibition of cell viability by buprenorphine was not affected by the caspase
      inhibitor. These findings suggest that some opioid analgesics induce typical
      apoptotic features sensitive to the caspase inhibitor, while also inhibition of
      cell viability insensitive to the inhibitor.

PMID- 10934300
TI  - Transplacental effects of maternal feeding with high fat diets on lipid exchange
      and response of the splenic lymphoid system in mice offspring exposed to low
      doses of carcinogen.
AB  - We studied whether feeding pregnant female mice with different fats affects lipid
      exchange and activity of the splenic lymphoid system in offspring exposed to low
      doses of carcinogen. Female mice were fed diets with either 7% or 15% corn oil or
      olive oil. The 4-week-old offspring of these mice were transferred to a chow
      diet, and exposed to a low dose of the carcinogen, dimethylbenz(a)antracene (2
      mg/kg). Results of experiments were studied 5 months later. Concentrations of
      polyunsaturated linoleic and oleic acids were determined in the blood and liver
      of mothers and offspring. The activity of the splenic immune system in offspring
      was studied using immunohistochemical methods for evaluating the number of
      different types of lymphocytes (B and T cells), mitotic and apoptotic indexes and
      the number of Fas-positive lymphocytes. Serum concentrations of the fatty acids
      examined were unchanged in the blood of the mothers and their offspring.
      Concentration of both linoleic and oleic acids was significantly higher in the
      liver of mothers fed the 15% olive-oil or corn-oil diets. This high level was
      maintained in linoleic acid in offspring of mothers fed the 15% olive-oil diet.
      Spleen weight was higher in offspring of mothers fed a 15% corn-oil diet compared
      to those fed the 7% corn-oil diet. The 15% olive-oil diet slightly decreased the
      weight of the spleen compared to counterparts fed the 15% corn-oil diet.
      Immunohistochemical studies showed that the olive diet, partially of 15%,
      significantly stimulated B-cell blast transformation. The finding reflects the
      reaction of B lymphocyte-producing splenic zones to the carcinogenic effect,
      though to a weak extent. T lymphocyte-producing zones did not respond to the
      diets studied, probably due to the weak carcinogenic effect and lack of tumor
      appearance. The Fas activity of both B and T cells in the spleen was stimulated
      by the carcinogen and enhanced by feeding the mothers on the olive-oil diet.
      Maternal feeding with a diet rich in olive oil before pregnancy results in
      stimulation of morphological and functional attributes of the splenic immune
      system of the offspring, particularly related to producing of B lymphocytes.

PMID- 10934302
TI  - Fifty-third World Health Assembly: impact on cardiovascular disease.

PMID- 10934303
TI  - Gone in sixty nanoseconds.

PMID- 10934304
TI  - Implantation of permanent pacemakers outside the operating room: is there cause
      for concern?

PMID- 10934305
TI  - Implantation of permanent pacemakers in the electrophysiology laboratory: what it
      has changed in a general teaching hospital.
AB  - BACKGROUND: Analysis of surveys concerning current practice in pacemaker
      implantation has shown a difference between the United States and Canada: almost
      70% of pacemakers are implanted in the operating room (OR) by surgeons in Canada,
      while in the United States, 70% of the implantations are done in a
      catheterization laboratory. OBJECTIVE: To analyze the impact (in terms of
      complications, time on the waiting list, length of hospitalization and costs) of
      moving surgery from the OR to the electrophysiology laboratory (EPL) in a 450-bed
      Canadian teaching hospital. Data were collected on 100 consecutive implantations
      in the OR and, subsequently, on 100 procedures in the EPL. RESULTS: The
      populations were identical in age (68+/-18 and 69+/-18 years, respectively) and
      sex ratio (both groups were 58% male). The implantation technique differed: the
      subclavian approach was used in 73% of patients in the OR group and in 99% of
      those in the EPL group. Antibiotic prophylaxis was given to all patients. The
      dual chamber rate was 22% in the OR group and 28% in the EPL group. Complication
      rates were similar in the two groups. Eleven per cent of procedures in the OR
      group and 46% in the EPL group were elective. For patients who underwent
      nonelective surgery, the time from indication to implantation was reduced from
      3.3+/-2.6 days in the OR group to 1. 9+/-1.8 days in the EPL group (P=0.0005),
      and the total stay in hospital was 10.2+/-7.4 days and 6.9+/-7.8 days,
      respectively (P=0. 01). For both elective and nonelective surgery, the total stay
      in hospital was 9.2+/-7.4 days in the OR group and 4.2+/-6.4 days in the EPL
      group (P<0.00001). The overall cost reduction, taking into account an arbitrary
      earlier discharge in the EPL group, was almost 50%. CONCLUSIONS: In this general
      teaching hospital, moving pacemaker implantation surgery from the OR to the EPL
      was safe and reduced by almost 50% the hospitalization stay by reducing the delay
      before implantation and by allowing elective surgery.

PMID- 10934306
TI  - Dyslipidemias and the primary prevention of cardiovascular disease: analysis of
      the FAMUS primary care register.
AB  - BACKGROUND: Primary prevention of cardiovascular disease with a pharmacological
      approach to dyslipidemias is controversial. Little is known about the clinical
      management by general practitioners in this area. OBJECTIVES: To evaluate the
      patterns of treatment of patients in primary prevention who were entered in the
      FAmily Medicine, Universite de Sherbrooke (FAMUS) register and to calculate the
      probability of their receiving a hypolipidemic agent according to the presence of
      various risk profiles. PATIENTS AND METHODS: Descriptive study based on the FAMUS
      prospective primary care register. Data from patients in primary prevention
      (those who had not sustained a cardiovascular event) were extracted and analyzed.
      MAIN RESULTS: Of the 52,505 patients in the register, 48, 190 were identified as
      being in primary prevention. Of these, 22,250 (46.2%) had a complete lipid
      profile on record, and 2300 had received a prescription for a hypolipidemic agent
      (4.8%). Patients under pharmacological treatment had significantly higher lipid
      values. The adjusted relative risk of being treated with a hypolipidemic agent
      was 1.3 for smokers, 1.3 for diabetic patients, 2.0 for those with a positive
      family history of premature cardiovascular disease, 2.2 for hypertensives and 3.3
      for men over 45 years of age or women over 55 years, compared with patients who
      were not taking lipid-lowering medications. The number of risk factors was even
      more strongly associated with the probability of being treated. CONCLUSION:
      Overall, few patients in primary prevention in the register were treated with a
      pharmacological agent. The presence of associated risk factors in this study was
      an important predictor for treatment, suggesting that patients in primary
      prevention are being evaluated globally as a function of all of their risk
      factors, not just their lipid and lipoprotein levels. Further attention,
      nonetheless, needs to be directed to the segment of the population with multiple
      risk factors whose lipoprotein profile is unknown or who are not being treated to
      guideline target levels.

PMID- 10934307
TI  - Maude E Abbott - physician and scientist of international fame.
AB  - Dr Maude E Abbott (1869 to 1940) is the only Canadian and the only woman
      represented in Diego Rivera's great mural of the History of Cardiology in Mexico
      City. She gained this place among the world's famous physicians and scientists by
      her outstanding studies of congenital heart disease. Her atlas of 1000 cases with
      clinical, pathological and morphological findings is the first systematic study
      of these anomalies. Dr Abbott developed a pathophysiological classification of
      cardiovascular defects fundamental for the development of cardiac surgery. She
      also considered prevention by prenatal care, recognizing possible genetic and
      environmental risk factors. Maude Abbott was a thoughtful clinician and a
      brilliant scientist of incomparable industry. She leaves an unfinished legacy to
      make the prevention of congenital heart disease a reality.

PMID- 10934308
TI  - Maude Abbott: a biography.
AB  - Maude Abbott was a pediatrician and cardiologist who spent her life working as a
      pathologist at McGill University, Montreal, Quebec and published over 100
      articles. Her magnum opus was The Atlas of Congenital Heart Disease, which listed
      a classification of cardiac disease based on 1000 pathological cases. Her work as
      a pathologist and her correlation of pathological samples with physical symptoms
      provided a foundation of the classification of heart disease and the medical
      surgical interventions. She also predicted causation and prevention. She
      introduced the use of pathological specimens to medical teaching. In addition to
      her papers on pathology, Abbott also published articles and books on the history
      of medicine. In January 2000, Canada Post produced a stamp as a tribute to her
      work.

PMID- 10934309
TI  - Endothelin receptor antagonists and their developing role in cardiovascular
      therapeutics.
AB  - Endothelin (ET) -1 is a potent vasoconstrictor and promitogenic peptide produced
      by the vascular endothelium. The ET system is activated in atherosclerosis and in
      most cardiovascular conditions associated with increased vascular tone and
      remodelling. There are two ET-receptor (ET-R) subtypes: the ETA-Rs mediate smooth
      muscle vasoconstriction and proliferation, and the more complex ETB-Rs have
      antagonistic actions - they serve a dual role of clearance and vasodilation in
      the endothelium, while in smooth muscle cells they also provoke vasoconstriction.
      Selective ETA-R and nonselective ETA/B-R antagonists are entering the clinical
      development phase. These agents have shown their effectiveness in the therapy of
      various models of heart failure, pulmonary hypertension, systemic hypertension
      and ischemia-reperfusion and in the prevention of restenosis. In patients with
      congestive heart failure, short term ET-antagonist (ET-R) therapy provides
      hemodynamic and symptomatic improvement. Because of the dual role of the ETB-R,
      nonselective antagonists may provide greater or fewer benefits than selective ETA
      R antagonists: a lack of direct comparison of the two categories of agents,
      however, does not allow this distinction at present. In the evaluation of this
      new class of therapeutic agents, particular attention should be paid to potency
      and receptor selectivity of a compound, the alterations in ETA-R and ETB-R
      activity brought on by pathological conditions, the proportions of ETA versus ETB
      R of the target system, and finally, the net importance of the possible
      protective role of the endothelial ETB versus the deleterious effects of the
      smooth muscle ETB-R.

PMID- 10934310
TI  - Intracoronary ultrasound imaging: methods and clinical applications.
AB  - OBJECTIVE: To review the development of intracoronary ultrasound, its current
      utility and the impetus for its continued development as a coronary imaging
      modality. DATA SOURCES: English-language literature (1966 to 1999) was searched
      in the MEDLINE database with the key words 'ultra- sound', 'intravascular' and
      'intracoronary', and limited to human studies. In addition, an online public
      access catalogue was searched using the subject headings 'cardiovascular diseases
      - therapy', 'heart diseases' and 'vascular diseases'. STUDY SELECTION AND DATA
      EXTRACTION: Articles relating to the history of intravascular or intracoronary
      ultrasound, methods and materials employed, advantages and disadvantages, safety
      issues and future directions of research in the area of intracoronary ultrasound
      were selected. DATA SYNTHESIS: Intracoronary ultrasound has been shown to improve
      upon demonstrated weaknesses of coronary angiography. This imaging technique,
      while invasive, has not been associated with significant, acute adverse effects
      and has proved to be useful in guiding interventions, and evaluating the
      mechanism and extent of their success. Technological limitations with respect to
      the equipment employed, and the acquisition, processing and display of images are
      the subject of intense research focus because they hinder more widespread
      clinical use of intracoronary ultrasound. CONCLUSIONS: Intracoronary ultrasound
      has emerged as a safe and useful tool in the visualization of the coronary
      vasculature. Technological limitations and questions about long term safety are a
      concern. Its ability to overcome the inherent limitations of coronary
      angiography, and to guide and evaluate coronary interventions supports the notion
      that this technique will continue to assume an ever-expanding role in
      interventional cardiology.

PMID- 10934311
TI  - Hydatid cyst of the heart located in the interventricular septum.
AB  - Cardiac hydatosis is a rare condition, and the localization of a hydatid cyst
      within the interventricular septum is exceptional. A 61-year-old man found to
      have a hydatid cyst of the interventricular septum is reported. Presenting
      manifestations were congestive heart failure and signs suggestive of an aortic
      valvulopathy. Diagnosis was made by Doppler echocardiography and confirmed by
      magnetic resonance imaging. The cyst was approached surgically by right
      ventriculotomy. Despite a technically successful intervention without rupture of
      the cyst or appearance of a conduction delay, the patient died on the 20th
      postoperative day because of acute respiratory distress syndrome complicating
      infectious pneumonia.

PMID- 10934312
TI  - Cardiac tamponade as the first clinical manifestation of metastatic
      adenocarcinoma of the lung.
AB  - A 62-year-old woman presented in the emergency department with new onset of
      dyspnea and clinical signs of cardiac tamponade. She had a history of cigarette
      smoking and a family history of adenocarcinoma, pancreatic and breast carcinoma.
      An emergency two-dimensional echocardiogram confirmed the diagnosis of cardiac
      tamponade. Therapeutic pericardiocentesis resulted in prompt relief. Cytology
      confirmed malignant glandular cells, consistent with a metastatic adenocarcinoma.
      Computerized chest tomography confirmed pulmonary involvement.

PMID- 10934313
TI  - Celebrating our heroes.

PMID- 10934314
TI  - Introduction-1890 to the present: beginning the third century of the growth cone

PMID- 10934315
TI  - Substrate-cytoskeletal coupling as a mechanism for the regulation of growth cone
      motility and guidance.
AB  - Growth cones are highly motile structures at the end of neuronal processes,
      capable of receiving multiple types of guidance cues and transducing them into
      directed axonal growth. Thus, to guide the axon toward the appropriate target
      cell, the growth cone carries out different functions: it acts as a sensor,
      signal transducer, and motility device. An increasing number of molecular
      components that mediate axon guidance have been characterized over the past
      years. The vast majority of these molecules include proteins that act as guidance
      cues and their respective receptors. In addition, more and more signaling and
      cytoskeleton-associated proteins have been localized to the growth cone.
      Furthermore, it has become evident that growth cone motility and guidance depends
      on a dynamic cytoskeleton that is regulated by incoming guidance information.
      Current and future research in the growth cone field will be focussed on how
      different guidance cues transmit their signals to the cytoskeleton and change its
      dynamic properties to affect the rate and direction of growth cone movement. In
      this review, we discuss recent evidence that cell adhesion molecules can regulate
      growth cone motility and guidance by a mechanism of substrate-cytoskeletal
      coupling.

PMID- 10934316
TI  - The clutch hypothesis revisited: ascribing the roles of actin-associated proteins
      in filopodial protrusion in the nerve growth cone.
AB  - We seek to understand how the nerve growth cone acts as a sensory motile machine
      to respond to chemical cues in the developing embryo. This review focuses on
      filopodial protrusion and F-actin-based motility because there is good evidence
      that these processes are required for axon guidance. The clutch hypothesis, which
      states that filopodial protrusion occurs by actin assembly when an actin filament
      is fixed with respect to the substrate (i.e., a clutch is engaged), was
      postulated by Mitchison and Kirscher to link protrusion to actin dynamics.
      Protrusion would require functional modules for movement of material into
      filopodia, clutching the F-actin, F-actin assembly at the tip, and retrograde
      flow. In this review, recent studies of actin-associated proteins involved in
      filopodial protrusion will be summarized, and their roles will be assessed in the
      context of the clutch hypothesis. The large number of proteins involved in
      filopodial motility and their complex interactions make it difficult to
      understand how these proteins act in protrusion. Recently, we have used
      microscale chromophore-assisted laser inactivation (micro-CALI) for the focal and
      acute inactivation of specific actin-associated proteins during filopodial
      protrusion to address their in situ roles. Our findings suggest that myosin V
      functions in moving membranes or other material forward in extending filopodia,
      that talin acts in the clutch module, and that zyxin acts in actin assembly at
      the tip during filopodial protrusion, perhaps by recruiting Ena/VASP family
      members to promote actin elongation at this site.

PMID- 10934318
TI  - Common mechanisms underlying growth cone guidance and axon branching.
AB  - During development, growth cones direct growing axons into appropriate targets.
      However, in some cortical pathways target innervation occurs through the
      development of collateral branches that extend interstitially from the axon
      shaft. How do such branches form? Direct observations of living cortical brain
      slices revealed that growth cones of callosal axons pause for many hours beneath
      their cortical targets prior to the development of interstitial branches. High
      resolution imaging of dissociated living cortical neurons for many hours revealed
      that the growth cone demarcates sites of future axon branching by lengthy pausing
      behaviors and enlargement of the growth cone. After a new growth cone forms and
      resumes forward advance, filopodial and lamellipodial remnants of the large
      paused growth cone are left behind on the axon shaft from which interstitial
      branches later emerge. To investigate how the cytoskeleton reorganizes at axon
      branch points, we fluorescently labeled microtubules in living cortical neurons
      and imaged the behaviors of microtubules during new growth from the axon shaft
      and the growth cone. In both regions microtubules reorganize into a more plastic
      form by splaying apart and fragmenting. These shorter microtubules then invade
      newly developing branches with anterograde and retrograde movements. Although
      axon branching of dissociated cortical neurons occurs in the absence of targets,
      application of a target-derived growth factor, FGF-2, greatly enhances branching.
      Taken together, these results demonstrate that growth cone pausing is closely
      related to axon branching and suggest that common mechanisms underlie directed
      axon growth from the terminal growth cone and the axon shaft.

PMID- 10934317
TI  - Regulating actin dynamics in neuronal growth cones by ADF/cofilin and rho family
      GTPases.
AB  - Growth cone motility and navigation in response to extracellular signals are
      regulated by actin dynamics. To better understand actin involvement in these
      processes we determined how and in what form actin reaches growth cones, and once
      there, how actin assembly is regulated. A continuous supply of actin is
      maintained at the axon tip by slow transport, the mobile component consisting of
      an unassembled form of actin. Actin is co-transported with actin-binding
      proteins, including ADF and cofilin, structurally related proteins essential for
      rapid turnover of actin filaments in vivo. ADF and cofilin activity is regulated
      through phosphorylation by LIM kinases, downstream effectors of the Rho family of
      GTPases, Cdc42, Rac and Rho. Attractive and repulsive extracellular guidance cues
      might locally alter actin dynamics by binding specific GTPase-linked receptors,
      activating LIM kinases, and subsequently modulating the activity of ADF/cofilin.
      ADF is enriched in growth cones and is required for neurite outgrowth. In
      addition, signals that influence growth cone behavior alter ADF/cofilin
      phosphorylation, and overexpression of ADF enhances neurite outgrowth. Growth
      promoting effects of laminin are mimicked by expression of constitutively active
      Cdc42 and blocked by expression of the dominant negative Cdc42. Repulsive effects
      of myelin and sema3D on growth cones are blocked by expression of constitutively
      active Rac1 and dominant negative Rac1, respectively. Thus a series of complex
      pathways must exist for regulating effectors of actin dynamics. The bifurcating
      nature of the ADF/cofilin phosphorylation pathway may provide the integration
      necessary for this complex regulation.

PMID- 10934319
TI  - Neurotrophins and the dynamic regulation of the neuronal cytoskeleton.
AB  - The morphology of neuronal axons and dendrites is dependent on the dynamics of
      the cytoskeleton. An understanding of neurodevelopment and adult neuroplasticity
      must therefore include a detailed description of the intrinsic and extrinsic
      mechanisms that regulate the organization and dynamics of actin filaments and
      microtubules. In this paper we review recent advances in the understanding of the
      dynamic regulation of neuronal morphology by interactions among cytoskeletal
      components and the regulation of the cytoskeleton by neurotrophins.

PMID- 10934320
TI  - Regulation of growth cone behavior by calcium: new dynamics to earlier
      perspectives.

PMID- 10934321
TI  - From the growth cone surface to the cytoskeleton: one journey, many paths.
AB  - The mechanisms that guide axons through a complex cellular landscape to reach
      appropriate target cells are central to our understanding of neural development.
      Decades of work suggest that guidance information is interpreted by signaling
      machinery that controls the complex and dynamic cytoskeleton at the growth cone
      leading edge. Recent insights from the areas of signal transduction and cell
      biology have identified a number of key components that play central roles in
      this chain of command, including members of the Ena/VASP and WASP family of
      proteins. Although our understanding of the precise mechanism by which these
      proteins control actin assembly is still incomplete, these players are emerging
      as potential sites of integration that translate convergent signals into
      directional cell movement. This brief review explores some of the most recent
      articles on this topic.

PMID- 10934322
TI  - The role of a LAR-like receptor tyrosine phosphatase in growth cone collapse and
      mutual-avoidance by sibling processes.
AB  - Among the many cells or parts of cells that a growth cone may encounter during
      its embryonic migrations are other processes or parts of its parent cell. Such an
      event can be expected to be relatively frequent in the genesis of neuronal
      arbors, for instance, where the density of innervation of a target region can be
      quite high. Few experimental studies have addressed the very interesting question
      of whether a process "recognizes" siblings in some unique way, in a manner that
      can be distinguished from, say, how it interacts with unrelated cells. One
      example can be found in the leech, where sibling branches in the terminal fields
      of identified mechanosensory cells avoid each other strictly while permitting
      some significant continuing contact and overlap with homologues, a phenomenon
      that has been dubbed "self-avoidance." Another example has been reported in
      cultured Helisoma neurons, where severing a branch of a neuron allows sibling
      neurites to form electrical junctions with it, although normally sibling neurites
      do not do so. In both of these instances, coincidental activity was proposed as
      one means to achieve recognition of self and as possibly leading to the blocking
      of a continuing interaction among the parts, although alternative explanations
      were indeed considered possible.

PMID- 10934323
TI  - The receptor tyrosine phosphatase CRYPalpha affects growth cone morphology.
AB  - During development of the nervous system receptor tyrosine kinases and receptor
      protein tyrosine phosphatases act in a coordinate way during axon growth and
      guidance. In the developing avian retinotectal system, many different receptor
      protein tyrosine phosphatases are expressed. Most of them have unknown functions.
      Retinal ganglion cells express at least three different members of this receptor
      family on their axons and growth cones: CRYPalpha, CRYP-2 and PTPmu. CRYPalpha
      interacts heterophilically with at least two different ligands found in the basal
      membranes of the retina and the optic tectum. To analyze the role of the
      CRYPalpha-ligand interaction, retinal ganglion cell axons were grown on retinal
      basal membranes (inner limiting membrane) and the receptor-ligand interaction was
      blocked from both the receptor side (by receptor specific antibodies) and from
      the ligand side by using a receptor-alkaline phosphatase fusion protein. Both of
      these treatments reduced average retinal axon length and induced a dramatic
      change in morphology of retinal ganglion cell growth cones on basal membranes,
      but not on other substrates like laminin, N-cadherin, matrigel- and detergent
      treated basal membranes. These results suggest that CRYPalpha and its ligand act
      as growth-promoting molecules during intraretinal axon growth.

PMID- 10934324
TI  - Molecular basis of semaphorin-mediated axon guidance.
AB  - The semaphorin family of proteins constitute one of the major cues for axonal
      guidance. The prototypic member of this family is Sema3A, previously designated
      semD/III or collapsin-1. Sema3A acts as a diffusible, repulsive guidance cue in
      vivo for the peripheral projections of embryonic dorsal root ganglion neurons.
      Sema3A binds with high affinity to neuropilin-1 on growth cone filopodial tips.
      Although neuropilin-1 is required for Sema3A action, it is incapable of
      transmitting a Sema3A signal to the growth cone interior. Instead, the
      Sema3A/neuropilin-1 complex interacts with another transmembrane protein, plexin,
      on the surface of growth cones. Certain semaphorins, other than Sema3A, can bind
      directly to plexins. The intracellular domain of plexin is responsible for
      initiating the signal transduction cascade leading to growth cone collapse, axon
      repulsion, or growth cone turning. This intracellular cascade involves the
      monomeric G-protein, Rac1, and a family of neuronal proteins, the CRMPs. Rac1 is
      likely to be involved in semaphorin-induced rearrangements of the actin
      cytoskeleton, but how plexin controls Rac1 activity is not known. Vertebrate
      CRMPs are homologous to the Caenorhabditis elegans unc-33 protein, which is
      required for proper axon morphology in worms. CRMPs are essential for Sema3A
      induced, neuropilin-plexin-mediated growth cone collapse, but the molecular
      interactions of growth cone CRMPs are not well defined. Mechanistic aspects of
      plexin-based signaling for semaphorin guidance cues may have implications for
      other axon guidance events and for the basis of growth cone motility.

PMID- 10934325
TI  - Dynamic regulation of cell adhesion molecules during axon outgrowth.

PMID- 10934326
TI  - The multiple decisions made by growth cones of RGCs as they navigate from the
      retina to the tectum in Xenopus embryos.
AB  - Retinal ganglion cells (RGCs) of Xenopus laevis send axons along a stereospecific
      pathway from the retina to their target the optic tectum. Viewed from the point
      of the growth cone, this journey is reflected by discrete processes of axon
      initiation, axon outgrowth, navigation, target recognition, and innervation.
      These processes are characterised by distinct signalling mechanisms that trigger
      dynamic changes in growth cone morphology and behavior. Here we review work
      primarily from our laboratory, examining these events from a cellular and
      molecular perspective, focusing on the roles of FGFs, netrins, receptors, and
      intracellular effectors.

PMID- 10934327
TI  - Growth cone form, behavior, and interactions in vivo: retinal axon pathfinding as
      a model.
AB  - Studies in vitro have revealed a great deal about growth cone behaviors,
      especially responses to guidance molecules, both positive and negative, and the
      signaling systems mediating these responses. Little, however, is known about
      these events as they take place in vivo. With new imaging methods, growth cone
      behaviors can be chronicled in the complex settings of intact or semi-intact
      systems. With the retinal projection through the optic chiasm as a model, we
      examined the hypothesis previously drawn from static material that growth cone
      form is position-specific: growth cone form in fact reflects specific behaviors,
      including rate and tempo of extension, that are more or less prominent in
      different locales in which growth cones are situated. Other studies show that
      growth cones interact with cells along the pathway, both specialized nonneuronal
      cells and other neurons, some expressing known guidance molecules. The present
      challenge is to bridge dynamic imaging with electron microscopy and molecular
      localization, in order to link growth cone behaviors with cell and molecular
      interactions in the natural setting in which growth cones extend.

PMID- 10934328
TI  - Mechanisms of growth cone guidance and motility in the developing grasshopper
      embryo.
AB  - During neuronal pathfinding in vivo, growth cones must reorient their direction
      of migration in response to extracellular guidance cues. The developing
      grasshopper limb bud has proved to be a model system in which to examine
      mechanisms of growth cone guidance and motility in vivo. In this review we
      examine the contributions of adhesion and multiple guidance cues (semaphorins 1
      and 2) in directing a growth cone steering event. Recent observations have
      suggested that the tibial pioneer growth cones are not directed via mechanisms of
      differential adhesivity. We present a model of growth cone steering that suggests
      a combination of adhesive and guidance receptors are important for a correct
      steering event and that guidance molecules may be important regulators of
      adhesive interactions with the actin cytoskeleton.

PMID- 10934329
TI  - Genetic analysis of growth cone migrations in Caenorhabditis elegans.
AB  - Model organisms like Caenorhabditis elegans allow the study of growth cone
      motility and guidance in vivo. We are using circumferential axon guidance in C.
      elegans to study both the mechanisms of guidance and the interactions between
      different guidance systems in vivo. A genetic screen has identified suppressors
      of the specific axon guidance defects caused by ectopic expression of UNC-5, the
      repulsive receptor for the UNC-6/netrin guidance cue. These mutations identify
      eight genes whose products are required for the function of UNC-5 in these cells.
      In principle, the functions of some of these genes may involve unc-73, which
      encodes a multidomain, cytoplasmic protein that is an activator of the rac and
      rho GTPases. Loss of UNC-73 causes errors in axon guidance, and it is
      hypothesized that UNC-73 acts in multiple signaling pathways used by guidance
      receptors on the growth cone surface to regulate the underlying cytoskeleton.
      Here we summarize and discuss these recent developments that are advancing our
      understanding of growth cone signal transduction in vivo.

PMID- 10934330
TI  - Interstitial fluid and hypoechoic wall: two sonographic signs of breast abscess.
AB  - PURPOSE: Many mammographic and sonographic features of breast abscess overlap
      with those of carcinoma. We reviewed the usefulness of interstitial fluid and
      hypoechoic walls in the sonographic diagnosis of breast abscess. METHODS: The
      sonograms and records of 65 patients with breast infection and 60 contemporaneous
      patients with breast cancer were retrospectively reviewed. RESULTS: Of 49
      abscesses identified in patients with breast infection, 14 (29%) had adjacent
      interstitial fluid that was sonographically visible, and 15 (31%) had a
      hypoechoic wall. No patients with breast cancer had either sign. The overall
      sensitivity of the presence of either sign was 55%, and the specificity was 100%.
      CONCLUSIONS: Two sonographic findings, interstitial fluid and a hypoechoic wall,
      are relatively specific for breast abscess and may aid in the diagnosis of breast
      disease.

PMID- 10934331
TI  - Sonographic and pathologic findings in typical and atypical medullary carcinomas
      of the breast.
AB  - PURPOSE: We investigated whether there was a relationship between the sonographic
      and histologic appearances of medullary carcinomas of the breast to determine
      whether sonography is helpful in the differentiation of typical and atypical
      medullary carcinomas. METHODS: We retrospectively reviewed the histologic slides
      and sonograms of 20 patients who had been diagnosed with medullary carcinoma of
      the breast. We then classified the carcinomas as typical or atypical based on
      strict histologic criteria. We also evaluated the relationship between
      sonographic findings and the histologic reclassification. RESULTS: Eight (40%) of
      the 20 medullary carcinomas were classified as typical, and 12 (60%) were
      classified as atypical. On sonography, a smooth outline was visualized in 6 (75%)
      of the 8 typical medullary carcinomas but in none of the 12 atypical carcinomas.
      A jagged margin was sonographically visualized in 10 (83%) of the 12 atypical
      carcinomas, and a focal irregularity in the margin was visualized in 2 (17%) of
      the 12 atypical carcinomas. Four of the typical medullary carcinomas had
      posterior enhancement, and 9 of the atypical medullary carcinomas showed
      retrotumoral shadowing. The difference in tumor-margin regularity between typical
      and atypical medullary carcinomas was found to be statistically significant (p <
      0.001) using the 2-tailed Fisher's exact test. CONCLUSIONS: To prevent
      overdiagnosis of medullary carcinoma, a thorough pathologic review of the entire
      tumor is recommended if sonography shows a jagged margin or a margin with focal
      irregularity.

PMID- 10934332
TI  - Color Doppler sonographic evaluation of spontaneous portosystemic shunts and
      inversion of portal venous flow in patients with cirrhosis.
AB  - PURPOSE: The aim of the study was to evaluate the usefulness of color Doppler
      sonography in the detection of spontaneous portosystemic shunts and abnormal
      blood flow direction in the portal vein in patients with cirrhosis. METHODS:
      Patients were 67 men and 42 women (mean age, 53 +/- 14 years) with cirrhosis
      confirmed by liver biopsy. All patients underwent abdominal gray-scale and color
      Doppler sonographic evaluations to detect the presence of spontaneous
      portosystemic shunts and to analyze portal vein blood flow direction. RESULTS:
      Spontaneous portosystemic shunts were found in 41 patients (38%), most often as
      splenorenal shunts (21%) and patent umbilical veins (14%). Less frequent were
      gastric collaterals, gallbladder varices, collaterals to thrombotic portal veins,
      mesoiliac shunts, and portorenal shunts to the right kidney. The presence of
      shunts was associated with that of esophageal varices (p < 0.01), ascites (p <
      0.01), and inversion of portal flow (p < 0. 001) but not with splenomegaly. The
      direction of portal venous flow was normal (hepatopetal) in 80 patients (73%),
      hepatofugal in 10 (9%), and bidirectional in 7 (6%); 12 patients (11%) had
      partial portal vein thrombosis. CONCLUSIONS: Portosystemic shunts and the
      direction of portal venous flow are important features in the sonographic
      diagnosis of portal hypertension.

PMID- 10934333
TI  - Sonographic features of acute colonic diverticulitis: the "dome sign".
AB  - PURPOSE: This study was performed to clarify the sonographic features of acute
      colonic diverticulitis to enable its differentiation from appendicitis. METHODS:
      Of 119 patients who were referred to our hospitals for lower abdominal pain
      between June 1997 and December 1998 and underwent sonography, 12 patients had a
      definitive diagnosis of acute colonic diverticulitis and 4 patients a tentative
      diagnosis. Seventy-eight patients were diagnosed as having acute appendicitis,
      confirmed by appendectomy. In the 16 patients with diagnoses of diverticulitis,
      the sonographic and clinical features of acute colonic diverticulitis were
      studied. RESULTS: Among the 12 patients with definitive diagnoses of acute
      colonic diverticulitis, sonographic findings included localized thickening of the
      colonic wall (100%) and a hemispheric mass (the "dome sign") protruding at the
      thickened colonic wall (100%) and consisting of a hypoechoic wall (100%) and a
      central echogenic area (66%). The presence of diverticula was confirmed by barium
      enema x-ray study in all 12 patients. The 4 patients with tentative diagnoses of
      acute colonic diverticulitis all had colonic wall thickening but no dome sign.
      Colonoscopy revealed colitis in 3 of these patients. All 16 patients recovered
      with conservative treatment, without laparotomy. CONCLUSIONS: Sonography was
      useful for differentiating acute colonic diverticulitis from appendicitis. The
      sonographic finding of the dome sign seems to be specific for acute colonic
      diverticulitis.

PMID- 10934335
TI  - Sonographic findings in renal parenchymal malacoplakia.
AB  - Malacoplakia of the kidney is a rare inflammatory disorder. We describe a case of
      bilateral renal malacoplakia in which the patient had diffuse involvement of the
      left kidney and a focal lesion in the right kidney. Sonography showed a diffusely
      echogenic, enlarged left kidney with loss of corticomedullary differentiation and
      a single anechoic lesion measuring 1.8 x 1.6 x 1.3 cm in the right kidney. A left
      nephrectomy was performed, and the right kidney was managed conservatively with
      sonographic monitoring.

PMID- 10934334
TI  - Relative risk of cancer in sonographically detected thyroid nodules with
      calcifications.
AB  - PURPOSE: The aim of this prospective study was to evaluate the significance of
      sonographically detected thyroid calcifications in the diagnosis of thyroid
      cancer. METHODS: One hundred eighty-eight patients with thyroid disease,
      including 37 with thyroid cancer, were included in the study. Each patient
      underwent preoperative, high-resolution sonography to evaluate the thyroid gland
      for the presence of calcifications. RESULTS: The highest incidence of
      calcification was found in thyroid cancer (54%), followed by multinodular goiter
      (40%), solitary nodular goiter (14%), and follicular adenomas (12%). The
      incidence of cancer was significantly higher in calcified nodules (29%) than in
      noncalcified nodules in the entire group (14%) (p = 0.019), with a relative risk
      of 2.5. In the group of solitary thyroid nodules, the incidence of cancer in the
      calcified nodules (55%) was higher than in the nodules without calcification
      (23%) (p = 0.016). Multiple noncalcified thyroid nodules harbored cancer in only
      5% of cases. Compared with multiple noncalcified thyroid nodules, the solitary
      calcified nodules demonstrated a relative risk of 22.8. In both the solitary and
      multiple nodules, the relative risk in the presence of calcification was about
      the same, around 4. Patients younger than 40 years with calcified nodules
      constituted a high-risk group, with a relative risk of 3.8 versus 2.5 in patients
      older than 40 years with calcified nodules. CONCLUSIONS: The detection of thyroid
      calcifications by sonography is diagnostically valuable, especially in cases
      involving a solitary nodule or a young person. The presence of calcifications in
      these cases should raise the suspicion of malignancy. The low incidence of cancer
      in patients with multiple noncalcified thyroid nodules suggests that a more
      conservative approach may be appropriate in such cases.

PMID- 10934336
TI  - Spontaneous rupture of hydronephrotic kidney during pregnancy: value of serial
      sonography.
AB  - Hydronephrosis during pregnancy is common but rarely results in renal rupture. We
      report an unusual case of spontaneous rupture of a hydronephrotic kidney during
      pregnancy. Although we could not predict the renal rupture on the basis of
      sonographic findings, serial sonography was useful in the early detection and
      management of the rupture.

PMID- 10934337
TI  - Doppler sonographic diagnosis of primary transitional cell carcinoma of the
      ureter.
AB  - Primary carcinoma arising in the urothelium of the ureter is rare, accounting for
      only 1% of all cancers of the upper urinary tract. We describe a case in which
      primary transitional cell carcinoma of the right ureter was sonographically
      detected in a 45-year-old woman. The mass exhibited tumoral vascularity on power
      Doppler sonography and spectral analysis.

PMID- 10934338
TI  - Pancreatic arteriovenous malformation presenting as cysts: Doppler sonographic
      diagnosis.
AB  - A 50-year-old man presented with multiple lesions resembling cysts throughout the
      pancreas on gray-scale sonography. Pulsatile blood flow detected within the
      lesions on color Doppler sonography led to the diagnosis of pancreatic
      arteriovenous malformation (PAVM). Most previously reported PAVMs have been
      described as having a poorly defined, reticular, or mosaic-like hypoechoic
      appearance on gray-scale sonography; the cystic appearance of the PAVM seen in
      our case is unusual.

PMID- 10934339
TI  - Transient appendiceal enlargement in a patient with colonic amebiasis:
      sonographic detection and follow-up.
AB  - A case of colonic amebiasis with no clinical signs of acute appendicitis but with
      sonographic visualization of an enlarged appendix is reported. As antiamebic
      therapy resolved the clinical signs and symptoms of the amebiasis, the
      sonographic appearance of the appendix returned to normal. Thus, an enlarged
      appendix does not necessarily indicate clinical appendicitis in patients with
      colonic amebiasis.

PMID- 10934340
TI  - Flow cytometry testing in PNH. How much is enough?

PMID- 10934341
TI  - Application of flow cytometry to the diagnosis of paroxysmal nocturnal
      hemoglobinuria.
AB  - Within the contemporary multitude of complex methods used in clinical flow
      cytometry, very few techniques exist which can be described as disease-specific
      diagnostic tests. Detection of glycophosphatidylinositol (GPI)-linked antigens on
      hematopoietic cells using monoclonal antibodies and flow cytometry forms the
      basis of a specific diagnostic test for paroxysmal nocturnal hemoglobinuria
      (PNH). Absent or markedly diminished expression of GPI-linked antigens is, in the
      appropriate clinical setting, specific for all patients with PNH. Clinically, PNH
      is a syndrome characterized by bone marrow failure, acquired hemolytic anemia,
      and a thrombotic tendency. The molecular genetic lesion responsible for this
      condition is a somatic mutation of the X-linked pig-a gene within a multipotent
      hematopoietic stem cell. Due to its rarity, delay in diagnosis is not uncommon
      for patients with PNH. Once a definitive diagnosis is established, this can make
      a considerable impact on patient management and prognosis. In this article, we
      review the complimentary roles that molecular biology and flow cytometry have
      played in unraveling the genotypic and phenotypic aspects of this unique
      condition.

PMID- 10934343
TI  - Proposed flow cytometric reference method for the determination of erythroid F
      cell counts.
AB  - BACKGROUND: Quantitation of adult erythrocytes (RBC) containing fetal hemoglobin
      (F cells) is of potential clinical utility in evaluating erythropoietic
      disorders, such as myelodysplasia and hemoglobinopathies, and in monitoring F
      cell augmenting therapy. F-cell counting methodologies include fluorescence
      microscopy and flow cytometry. Previous flow cytometric methods have employed an
      isotype antibody control to distinguish F cells from non-F cells. We investigated
      the feasibility of using the orange autofluorescence signal (FL2) in
      glutaraldehyde-fixed RBC to substitute for fluorescein isothiocyanate (FITC)
      labeled isotype control antibody use in F-cell quantitation. METHODS: Our
      previously published method for fetal red cell detection in fetomaternal
      hemorrhage was used, employing a FITC-labeled anti-hemoglobin F (HbF) monoclonal
      antibody reagent. Blood samples with varying F-cell counts were quantitated for F
      cells using both immunofluorescence microscopy and flow cytometry comparing FITC
      labeled isotype to FL1 thresholding defined by FL2 autofluorescence. RESULTS: F
      cell percentages obtained by using an FL2 defined threshold for FL1 gating
      correlated well with expected values in diluted blood samples (r(2) = 0.994,
      slope = 1. 019, intercept = 0.24), values obtained using an isotype control (r(2)
      = 0.996, slope = 1.012, intercept = -0.17), and microscopic immunofluorescence
      counts (r(2) = 0.989, slope = 0.999, intercept = -0.72). F-cell quantitation by
      the isotype control and FL2 autofluorescence methods was also comparable in 40
      blood samples (r(2) = 0.994, slope = 1.014, intercept = 0.03). Intra-assay,
      interobserver, and interinstrument precision with this autofluorescence gating
      method exhibited low imprecision (coefficient of variation <14%). CONCLUSION:
      This novel method is a more objective and less laborious alternative for F-cell
      quantitation by flow cytometry compared to using an isotype control or
      microscopy, thereby providing a more robust methodology for clinical studies and
      consideration as a laboratory reference method for F-cell counting.

PMID- 10934342
TI  - Flow cytometric analysis of glycosylphosphatidyl-inositol-anchored proteins to
      assess paroxysmal nocturnal hemoglobinuria clone size.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by total or partial
      deficiency of membrane proteins anchored to the cell surface through a
      glycosylphosphatidyl-inositol (GPI) moiety. The relationship between the size of
      the PNH clone, determined by the expression of GPI-anchored proteins (AP; CD14,
      CD48, CD55, CD59, and CD66b) on erythrocytes, lymphocytes, monocytes, and
      granulocytes using forward and side scatter analysis, and severity of the disease
      was evaluated in 19 PNH patients. CD55 antigen expression did not delineate
      abnormal erythrocytes as well as did anti-CD59. The proportion of monocytes
      deficient in CD55, CD59, CD48, and CD14 (48-97%) and of granulocytes deficient in
      CD55, CD59, and CD66b (60-99%) was greater than the proportion of erythrocytes
      deficient in CD59 (24-95%) and the proportion of lymphocytes deficient in CD55
      and CD59 (30-98%). There were no significant correlations among reticulocyte,
      leukocyte, and platelet counts and GPI-AP-deficient immunophenotypes in red and
      white blood cells. However, high coefficients of determination were seen between
      hemoglobin levels and granulocytes deficient in CD59 (r(2) = 0.76), CD55 (r(2) =
      0.74), and CD66b (r(2) = 0.74) antigens and between hemoglobin and monocytes
      deficient in CD55 (r(2) = 0.73), CD59 (r(2) = 0.80), and CD14 (r(2) = 0.75)
      antigens. These results are interpreted as indicating that the size of PNH clone
      is better assessed by immunophenotypic analysis of monocytes and granulocytes
      rather than of lymphocytes and erythrocytes.

PMID- 10934344
TI  - Shift of aberrant antigen expression at relapse or at treatment failure in acute
      leukemia.
AB  - The flow cytometric detection of aberrant antigen expression is one method
      proposed for the quantification of minimal residual disease (MRD) in acute
      leukemias. The present study was designed to investigate the stability of the
      aberrant antigen expression at relapse or at treatment failure of initial
      chemotherapy. For this purpose, multiparameter immunophenotyping with a panel of
      15 monoclonal antibodies was used at diagnosis as well as at relapse (43 patients
      with overall 65 aberrations) and at treatment failure (35 patients with overall
      66 aberrations). There was a significant decrease in the percentage of the
      initially described aberrant antigen expression on leukemia blasts at relapse (P
      = 0.001; n = 65) as well as at treatment failure (P = 0.0001; n = 66) considering
      all aberrations in the whole leukemia population. Concerning only patients with
      acute myelogenous leukemia (AML), significant decreases in the aberrant
      expression could be detected at relapse (P = 0.031; n = 42) and at treatment
      failure (P = 0.0001; n = 52). The changes in patients with acute lymphoblastic
      leukemia (ALL) were significant only at relapse (P = 0.006; n = 23). Initially,
      the most informative aberration was not detectable in four patients at relapse
      and in seven patients at treatment failure. A decrease of under 50% of the
      initial value was observed in another 8 patients at relapse and in 10 patients at
      treatment failure. In further studies assessing the detection of aberrant antigen
      expression for MRD, quantification of the relapses should be explicitly analyzed
      regarding the persistence of the initially described aberrant antigen expression.

PMID- 10934346
TI  - Forum: journal club

PMID- 10934345
TI  - Cyclins of phases G1, S and G2/M are overexpressed in aneuploid mammary
      carcinomas.
AB  - Expression of cyclins A, B1 and D1 in human breast cancer was analyzed using dual
      parameter flow cytometry with simultaneous evaluation of the DNA content. The
      asynchronous MCF-7 breast adenocarcinoma cells were used to implement flow
      cytometry analysis and to analyze the cell cycle distribution of cyclins. The
      patterns of the cyclin expression were also analyzed in vivo in fresh tissue
      specimens of human breast carcinomas. The combined measurement of DNA and cyclins
      showed a higher cyclin expression in aneuploid (11.5 +/- 2.0%, 4.3 +/- 1.1%, and
      19.5 +/- 3.4% positive cells for cyclins A, B, and D1, respectively) than in
      diploid carcinomas (3.9 +/- 1.2%, 1.1 +/- 0.4%, and 5.0 +/- 1.2% positive cells
      for cyclins A, B, and D1, respectively). A positive relationship was also found
      between cyclin A and D1 expression and H(3)-thymidine labeling index. In the in
      vitro model, the asynchronous growing MCF-7 cells showed a variable number of
      cells expressing cyclins in an unscheduled way, unrelated to the phase at which
      these cyclins are expressed in normal cells. A similar condition was also
      observed in tumors. In conclusion, the data showed a deregulated expression of
      cyclins in a transformed adenocarcinoma cell line and in breast tumors.
      Furthermore, overexpression of these proteins is related to the aneuploid and
      high proliferative activity of human mammary carcinomas.

PMID- 10934347
TI  - Current lead natural products for the chemotherapy of human immunodeficiency
      virus (HIV) infection.
AB  - A large variety of natural products have been described as anti-HIV agents, and
      for a portion thereof the target of interaction has been identified. Cyanovirin
      N, a 11-kDa protein from Cyanobacterium (blue-green alga) irreversibly
      inactivates HIV and also aborts cell-to-cell fusion and transmission of HIV, due
      to its high-affinity interaction with gp120. Various sulfated polysaccharides
      extracted from seaweeds (i.e., Nothogenia fastigiata, Aghardhiella tenera)
      inhibit the virus adsorption process. Ingenol derivatives may inhibit virus
      adsorption at least in part through down-regulation of CD4 molecules on the host
      cells. Inhibition of virus adsorption by flavanoids such as (-)epicatechin and
      its 3-O-gallate has been attributed to an irreversible interaction with gp120
      (although these compounds are also known as reverse transcriptase inhibitors).
      For the triterpene glycyrrhizin (extracted from the licorice root Glycyrrhiza
      radix) the mode of anti-HIV action may at least in part be attributed to
      interference with virus-cell binding. The mannose-specific plant lectins from
      Galanthus, Hippeastrum, Narcissus, Epipac tis helleborine, and Listera ovata, and
      the N-acetylgl ucosamine-specific lectin from Urtica dioica would primarily be
      targeted at the virus-cell fusion process. Various other natural products seem to
      qualify as HIV-cell fusion inhibitors: the siamycins [siamycin I (BMY-29304),
      siamycin II (RP 71955, BMY 29303), and NP-06 (FR901724)] which are tricyclic 21
      amino-acid peptides isolated from Streptomyces spp that differ from one another
      only at position 4 or 17 (valine or isoleucine in each case); the betulinic acid
      derivative RPR 103611, and the peptides tachyplesin and polyphemusin which are
      highly abundant in hemocyte debris of the horseshoe crabs Tachypleus tridentatus
      and Limulus polyphemus, i.e., the 18-amino-acid peptide T22 from which T134 has
      been derived. Both T22 and T134 have been shown to block T-tropic X4 HIV-1
      strains through a specific antagonism with the HIV corecept or CXCR4. A number of
      natural products have been reported to interact with the reverse transcriptase,
      i.e., baicalin, avarol, avarone, psychotrine, phloroglucinol derivatives, and, in
      particular, calanolides (from the tropical rainforest tree, Calophyllum
      lanigerum) and inophyllums (from the Malaysian tree, Calophyllum inophyllum). The
      natural marine substance illimaquinone would be targeted at the RNase H function
      of the reverse transcriptase. Curcumin (diferuloylmethane, from turmeric, the
      roots/rhizomes of Curcuma spp), dicaffeoylquinic and dicaffeoylt artaric acids, L
      chicoric acid, and a number of fungal metabolites (equisetin, phomasetin,
      oteromycin, and integric acid) have all been proposed as HIV-1 integrase
      inhibitors. Yet, we have recently shown that L-c hicoric acid owes its anti-HIV
      activity to a specific interaction with the viral envelope gp120 rather than
      integrase. A number of compounds would be able to inhibit HIV-1 gene expression
      at the transcription level: the flavonoid chrysin (through inhibition of casein
      kinase II, the antibacter ial peptides melittin (from bee venom) and cecropin,
      and EM2487, a novel substance produced by Streptomyces. (ABSTRACT TRUNCATED)

PMID- 10934348
TI  - PPAR agonists as direct modulators of the vessel wall in cardiovascular disease.
AB  - Successful management of cardiovascular (CV) disease and associated metabolic
      syndromes, such as diabetes, is a major challenge to the clinician. Reducing CV
      risk factors, such as abnormal lipid profiles, insulin resistance or hypertension
      is the foundation of such therapy. A relatively new class of therapeutic agent,
      activators of peroxisome proliferator-activated receptors (PPAR), is poised to
      make a major impact with regard to several areas of risk factor management.
      However, there is growing evidence that PPAR agonists may also influence the CV
      system directly by modulating vessel wall function. These observations suggest
      that additional benefit, in the treatment of CV disease, may derive not only from
      the ability of agents to modify risk factors but also to influence directly the
      cellular mechanisms of disease within the vessel wall. A precedent for this dual
      action comes from examination of the effects of inhibitors of HMG CoA reductase
      (statins), where risk factor modulation is accompanied by direct actions on the
      vessel wall. In this review, we summarize the evidence suggesting that PPAR
      agonists may directly modulate vessel wall function, and that these may parallel
      those effects reported recently for the statins.

PMID- 10934349
TI  - Targeting drugs to the brain by redox chemical delivery systems.
AB  - Chemical delivery systems (CDSs) based on the redox conversion of a lipophilic
      dihydropyridine to an ionic, lipid-insoluble pyridinium salt have been developed
      to improve the access of therapeutic agents to the central nervous system. A
      dihydropyridinium-type CDS or a redox analog of the drug is sufficiently
      lipophilic to enter the brain by passive transport, then undergoes an enzymatic
      oxidation to an ionic pyridinium compound, which promotes retention in the CNS.
      At the same time, peripheral elimination of the entity is accelerated due to
      facile conversion of the CDS in the body. This review discusses chemical,
      physicochemical, biochemical, and biological aspects in relation to the
      principles and practical implementation of the redox brain-targeting approach to
      various classes of drugs. Representative examples to the brain-enhanced delivery
      of neurotransmitters, steroids, anticonvulsants, antibiotics, antiviral,
      anticancer and antidementia agents, and neuropeptides and their analogs are
      presented in detail. In vivo and in vitro studies and preliminary clinical data
      of several novel derivatives have been promising, which could lead to a practical
      use of the redox CDSs after proper pharmaceutical development. The investigations
      accentuate the need for considering physicochemical, metabolic, and
      pharmacokinetic properties in designing of carrier systems that are able to
      target drugs into the central nervous system.

PMID- 10934351
TI  - Innovation in Crop Protection: Trends in Research.
AB  - In the absence of the remarkable levels of growth in the yields of important
      crops, neither the rapid increase in living standards in industrialized countries
      nor the adequate standard of nutrition for the greater part of the world's
      population would have been possible. Alongside high-yielding varieties, improved
      agricultural techniques, and rapid mechanization, the chemical industry has also
      contributed substantially to progress in agriculture since roughly the middle of
      the nineteenth century. From the chemists "kitchens" came two "magic weapons":
      artificial fertilisers and chemical agents for crop protection. Today both have
      become indispensable to modern yield- and quality-orientated agriculture. This
      review spans the development of the crop-protection industry from its earliest
      beginnings to the present day and attempts to portray how the research-based crop
      protection industry is prepared for current and future challenges. Considerable
      space is thus dedicated to the discussion of trends in research.

PMID- 10934352
TI  - Scanning Near-Field Optical Microscopy and Spectroscopy as a Tool for Chemical
      Analysis.
AB  - Research into the nanometer-scale region is currently of relevance in many
      branches of modern science and engineering, such as in microelectronics,
      supramolecular chemistry, and in a biological context. A great deal of attention
      is given to the design of molecular devices, usually towards understanding the
      function of existing "molecular machines". Central to this task are powerful
      diagnostic tools capable of recording chemical information with spatial
      resolution in the nanometer range. While elemental analysis of surfaces with a
      lateral resolution of a few dozen nanometers is almost routine, analysis of
      molecular species with a resolution of <1 um is very difficult. Scanning
      tunneling and atomic-force microscopies usually do not give any chemical
      information. By combining scanning near-field optical microscopy (SNOM)-the
      "optical member" of the family of scanning-probe microscopies-with optical
      spectroscopy, it is possible to obtain molecular information from sample areas as
      little as 50 nm in diameter. In SNOM, a light source is scanned above the object
      of interest at a distance of a few nanometers. In the optical near field, the
      illuminated area is not subject to the Abbe diffraction limit, but merely by the
      size of the illuminating source. High quality SNOM probes can be reproducibly
      prepared by a chemical-etching method. These etched probes have an optical
      transmission up to 1000-fold higher than commercial (pulled) SNOM tips and can
      withstand higher laser power. This last advantage allows not only high resolution
      optical imaging, but also localized spectroscopic investigations of surfaces and
      even optical "nanosampling" by pulsed-laser ablation. The ablated material can be
      transported over a considerable distance, which opens the possibility for its
      subsequent analysis with a complementary, highly sensitive analytical method,
      such as mass spectrometry.

PMID- 10934354
TI  - Giant Porphyrinoids: From Figure Eights to Nanomolecular Cavities.

PMID- 10934353
TI  - On Closed-Shell Interactions, Polar Covalences, d Shell Holes, and Direct Images
      of Orbitals: The Case of Cuprite Discussions with Professors and Doctors G. von
      Bunau, B. Engelen, H. D. Lutz, J. Niu-Schwarz, and A. Pfitzner (Siegen, Germany),
      R. Hoffmann (Ithaka, NY, USA), C. J. Humphreys (Cambridge, UK), A. Kirfel (Bonn,
      Germany), T. Lippman and J. Schneider (Hamburg, Germany), K. Schwarz (Vienna,
      Austria), M. Spackman (Armidale, Australia), J. C. H. Spence, M. O'Keefe and J.
      M. Zuo (Tempe AZ, USA), and financial support by Deutsche Forschungsgemeinschaft
      (DFG) and by Fonds der Chemischen Industrie (FCI) are all gratefully
      acknowledged.

PMID- 10934355
TI  - The Tumor Suppressor p53 in the Center of a Strategy Aiming at the Alleviation of
      Side Effects in Cancer Therapies.

PMID- 10934356
TI  - Poly(polyoxometalate) Dendrimers: Molecular Prototypes of New Catalytic Materials
      This work was supported by the U.S. Army Research Office. We thank Dr. G. R.
      Baker for providing the dendritric samples and Dr. Ira A. Weinstock for
      discussions.

PMID- 10934357
TI  - Dimerization of an Inactive Fragment of Huperzine A Produces a Drug with Twice
      the Potency of the Natural Product This work was supported by the Research Grants
      Council of Hong Kong (HKUST6156/97M), the Biotechnology Research Institute
      (HKUST), the Mayo Foundation, and the Istituto Pasteur Fondazione Cenci
      Bolognetti (E.P.). We thank Prof. X. C. Tang (Shanghai Institute of Materia
      Medica) for a gift of (-)-1.

PMID- 10934358
TI  - Naked-Eye Detection of Anions in Dichloromethane: Colorimetric Anion Sensors
      Based on Calix

PMID- 10934359
TI  - Photoacid-Induced Fluorescence Quenching: A New Strategy for Fluorescent Imaging
      in Polymer Films The authors thank the Korea Ministry of Science and Technology
      for financial support (KIST 2V00363).

PMID- 10934360
TI  - Halogen Bonding versus Hydrogen Bonding in Driving Self-Assembly Processes
      Perfluorocarbon-hydrocarbon self-assembly, part IX. This work was supported by
      MURST (Cofinanziamento '99) and EU (COST-D12-0012). We thank Dr. A. Lunghi and
      Dr. P. Cardillo (Stazione Sperimentale Combustibili, S. Donato Milanese, Italy)
      for ARC experiments. Part VIII: ref. 9.

PMID- 10934361
TI  - Spin-Density Map of the Triplet Ground State of a Titanium(IV) Complex with
      Schiff-Base Diquinone Radical Ligands: An Investigation Using Polarized-Neutron
      Diffraction and Density-Functional Theory This work was supported by the 3MD EU
      network (contract ERB 4061 PL 97-0197).

PMID- 10934362
TI  - A Novel Solid-Phase Assembly for Identifying Potent and Selective RNA Ligands We
      thank Professors David Wilson and David Boykin for a generous gift of the
      aromatic amidine derivatives and Professor Kol for a generous gift of eilatin
      containing complexes. We are grateful to Dr. Georg Schlechtingen and Professor
      Murray Goodman for assistance with peptide synthesis and to Ibis Therapeutics for
      partial support. N.W.L. is supported by a National Institute of Health Molecular
      Biophysics Training Grant (GM 08326).

PMID- 10934363
TI  - 3,3'-Azobis(6-amino-1,2,4,5-tetrazine): A Novel High-Nitrogen Energetic Material
      This work was supported at Los Alamos by the joint program of the Department of
      Defense and the Department of Energy for the preparation and characterization of
      new energetic materials, and at the Naval Research Laboratory by the Office of
      Naval Research, Mechanics Division.

PMID- 10934364
TI  - Synthesis of Prussian Blue Nanoparticles and Nanocrystal Superlattices in Reverse
      Microemulsions We thank the Swiss National Science Foundation for a postdoctoral
      fellowship to S.V. and the University of Bristol for a postgraduate studentship
      to M.L.

PMID- 10934365
TI  - Synthesis and Characterization of Ph(4)Te(4)I(4), Containing a Te(4) Square, and
      Ph(3)PTe(Ph)I.

PMID- 10934366
TI  - Highly Enantioselective Aldol Reaction with 2-Trimethylsilyloxyfuran: The First
      Catalytic Asymmetric Autoinductive Aldol Reaction The authors wish to thank J. C.
      Jullian for his help in NMR experiments, Dr. X. Franck for stimulating
      discussions, and Prof. R. Hocquemiller for his continuous interest in this study.
      Thanks are due to M.J. Vega Capela for the experiments with heptadecanal. L.
      Tache and B. Mbeninack are acknowledged for the preparation of the (R,R)-2
      isomer.

PMID- 10934367
TI  - Interconversion between u-eta(2),eta(2)-C(60) and u(3)-eta(2),eta(2),eta(2)-C(60)
      on a Carbido Pentaosmium Cluster Framework We are grateful to the Korea Science
      Engineering Foundation (KOSEF) for financial support (project no. 1999-1-122-001
      5) of this research and a postdoctoral fellowship to K.L. The X-ray diffraction
      studies were carried out at the X-ray Crystallographic Laboratory of Yonsei
      University, which was supported in part by KOSEF.

PMID- 10934368
TI  - Preparation, Structure, and Redox Reactions of Nine-Membered Cyclic Peroxides: A
      Novel Electrochromic System Undergoing Reversible Extrusion and Trapping of O(2)
      This work was supported by the Ministry of Education, Science, and Culture, Japan
      (No. 10146101). Financial support by the Izumi Science and Technology Foundation
      and by a Research Grant from the Iwatani Naoji Foundation (T.S.) are gratefully
      acknowledged. J.N. thanks JSPS Research Fellowships for Young Scientists. We
      thank Prof. Tamotsu Inabe (Hokkaido University) for the use of facilities to
      analyze the X-ray structures. Technical support by Mr. Kenji Watanabe and Dr. Eri
      Fukushi (GC-MS & NMR Laboratory, Faculty of Agriculture, Hokkaido University) is
      gratefully acknowledged.

PMID- 10934369
TI  - A New Asymmetric Carbon-Carbon Bond Forming Reaction: Four-Component
      Stereoselective Synthesis of (Z)-4,6-Dihydroxy-3-methylalk-2-enyl Methyl Sulfones
      This work was supported by the Swiss National Science Foundation.

PMID- 10934370
TI  - Metamorphic Channels in Periodic Mesoporous Methylenesilica This work was
      supported by the NSERC of Canada. M.J.M. is grateful to NSERC for postgraduate
      (1995-1999) and postdoctoral fellowships (1999-2001). G.A.O. thanks the Killam
      Foundation for the award of an Isaac Walton Killam research fellowship (1995
      1997).

PMID- 10934371
TI  - Electropolymerization of pi-Conjugated Oligomers Containing Phosphole Cores and
      Terminal Thienyl Moieties: Optical and Electronic Properties We thank the CNRS,
      the MENRT, the Conseil Regional de Bretagne for financial support of this work
      and Prof. C. Moinet for helpful discussions.

PMID- 10934372
TI  - The First Structurally Characterized Metal-SeH Compounds:

PMID- 10934373
TI  - Synthesis and Crystal Structure of a Cumulenic Quinoidal Porphyrin Dimer with
      Strong Electronic Absorption in the Infrared We thank the Engineering and
      Physical Sciences Research Council (UK) and the Defence Evaluation and Research
      Agency (DERA, UK) for support and the EPSRC Mass Spectrometry Service in Swansea
      for FAB mass spectra.

PMID- 10934374
TI  - Fully Reversible Cyclic Dimerization of Diphosphanylketenimines Promoted by
      Intramolecular C-H small middle dot small middle dot small middle dotN Hydrogen
      Bonds This work was supported by the Spanish Ministerio de Educacion y Ciencia
      (project nos. DGE-96-PB-0317 and PB96-0556).

PMID- 10934375
TI  - Dianionic Homoleptic Biphosphinine Complexes of Group 4 Metals This work was
      supported by the CNRS and the Ecole Polytechnique.

PMID- 10934376
TI  - Investigation of Electronic Communication and Guest Inclusion Using
      Photoluminescent Macrocyclic Receptors with Ru(II) Centers and Ph(2)P-C identical
      withC-C identical withC-PPh(2) Spacers This work was supported by the US National
      Science Foundation CAREER Award (CHE-9733546).

PMID- 10934377
TI  - The Absolute Configuration and Asymmetric Total Synthesis of the CP Molecules (CP
      263,114 and CP-225,917, Phomoidrides B and A) We thank Drs. D. H. Huang, G.
      Siuzdak, and R. Chadha for assistance with NMR spectroscopy, mass spectrometry,
      and X-ray crystallography, respectively. This work was financially supported by
      the National Institutes of Health (USA), The Skaggs Institute for Chemical
      Biology, doctoral fellowships from the National Science Foundation (P.S.B.) and
      Boehringer Ingelheim (Y.H.), and grants from Array Biopharma, Boehringer
      Ingelheim, Schering Plough, Pfizer, Glaxo, Merck, Hoffmann-La Roche, DuPont, and
      Abbott Laboratories.

PMID- 10934378
TI  - An Iron Wheel on a Tin Drum: A Novel Assembly of a Hexaferrocene Unit on a Tin
      Oxygen Cluster This work was supported by the Department of Science and
      Technology, New Delhi (grant to V.C.). V.C. is also grateful to the the Homi
      Bhabha Fellowship Council for a fellowship. The National Science Foundation (USA)
      is thanked for the purchase of an X-ray machine (grant CHE-9709005 to D.P.).

PMID- 10934379
TI  - Molecular Signal Transduction through Conformational Transmission of a
      Perhydroanthracene Transducer This work was supported by the Deutsche
      Forschungsgemeinschaft and the Fonds der Chemischen Industrie. Support by the NMR
      group of Dr. C. Mugge is gratefully acknowledged.

PMID- 10934380
TI  - Lithium, Sodium, and Copper(I) Supersilylphosphanediides M(2)PSitBu(3): Compounds
      with Novel Spherical (M(2)P)(n) Frameworks Compounds of Silicon, Part 133;
      Supersilyl Compounds of Phosphorus, Part 6. This work was supported by the
      Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen Industrie. Part
      132: N. Wiberg, T. Passler, S. Wagner, J. Organomet. Chem. 2000, 598/2, 304; Part
      5: N. Wiberg, A. Worner, H.-W. Lerner, K. Karaghiosoff, H. Noth, Z. Naturforsch.
      B 1998, 53, 1004.

PMID- 10934381
TI  - Confinement of

PMID- 10934382
TI  - Globular Amphiphiles: Membrane-Forming Hexaadducts of C(60) This work was been
      supported by the Deutsche Forschungsgemeinschaft and by the Fonds der Chemischen
      Industrie. We thank Dr. K. Fischer and Prof. Dr. K. Schmidt from the Institute of
      Physical Chemistry at the University of Mainz for performing the light scattering
      measurements.

PMID- 10934383
TI  - In Situ Monitoring of a Heterogeneous Palladium-Based Polyketone Catalyst We
      thank Dr. H. P. C. E. Kuipers for his stimulating interest, the members of the
      Carilon Polymer Team within Shell for valuable discussions, and Shell
      International Chemicals B.V. for giving permission to publish this paper.

PMID- 10934384
TI  - Induction of Lamellar Mesomorphic Structures in Columnar-Phase-Forming 1,3,5
      Triazines through Charge-Transfer Interactions with Electron Acceptors This work
      was supported by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen
      Industrie. D.J. is very grateful to Prof. C. Tschierske, Martin-Luther
      Universitat Halle, Germany, for helpful discussions.

PMID- 10934385
TI  - Combinatorial Surface Chemistry-Is it Possible? The authors thank the Charles E.
      Culpeper Foundation for the financial support of this work.

PMID- 10934386
TI  - Selenium-Bridged Gold(I) Complex Cations

PMID- 10934387
TI  - Channel-Forming Peptaibols Are Potent Elicitors of Plant Secondary Metabolism and
      Tendril Coiling We gratefully acknowledge the gift of ampullosporin A,
      bergofungins A-C, and the chrysospermins from Prof. U. Grafe (Hans-Knoll
      Institute for Natural Products Research, Jena), and we thank Dr. T. Nurnberger
      (Institute for Plant Biochemistry, Halle) for a sample of systemin.

PMID- 10934388
TI  - Sol-Gel Polycondensation of Tetraethoxysilane in a Cholesterol-Based Organogel
      System Results in Chiral Spiral Silica.

PMID- 10934390
TI  - Femtochemistry: Atomic-Scale Dynamics of the Chemical Bond Using Ultrafast Lasers
      (Nobel Lecture) Copyright((c)) The Nobel Foundation 2000. We thank the Nobel
      Foundation, Stockholm, for permission to print this lecture.
AB  - Over many millennia, humankind has thought to explore phenomena on an ever
      shorter time scale. In this race against time, femtosecond resolution (1 fs=10(
      15) s) is the ultimate achievement for studies of the fundamental dynamics of the
      chemical bond. Observation of the very act that brings about chemistry-the making
      and breaking of bonds on their actual time and length scales-is the wellspring of
      the field of femtochemistry, which is the study of molecular motions in the
      hitherto unobserved ephemeral transition states of physical, chemical, and
      biological changes. For molecular dynamics, achieving this atomic-scale
      resolution using ultrafast lasers as strobes is a triumph, just as X-ray and
      electron diffraction, and, more recently, STM and NMR spectroscopy, provided that
      resolution for static molecular structures. On the femtosecond time scale, matter
      wave packets (particle-type) can be created and their coherent evolution as a
      single-molecule trajectory can be observed. The field began with simple systems
      of a few atoms and has reached the realm of the very complex in isolated,
      mesoscopic, and condensed phases, as well as in biological systems such as
      proteins and DNA structures. It also offers new possibilities for the control of
      reactivity and for structural femtochemistry and femtobiology. This anthology
      gives an overview of the development of the field from a personal perspective,
      encompassing our research at Caltech and focusing on the evolution of techniques,
      concepts, and new discoveries.

PMID- 10934391
TI  - Acetylenic Coupling: A Powerful Tool in Molecular Construction.
AB  - Acetylenic coupling is currently experiencing some of the most intensive study of
      its long history. Rigid and sterically undemanding di- and oligoacetylene
      moieties, which are frequently encountered in natural products, are finding
      increasing application as key structural elements in synthetic receptors for
      molecular recognition. Interesting electronic and optical properties of
      extensively pi-conjugated systems have spurred research into new linear
      oligoalkynes and acetylenic carbon allotropes. The synthetic challenges
      associated with these efforts have in turn spawned new methods. While classical
      Glaser conditions are still frequently used for homocoupling, the demand for
      increasingly selective heterocoupling conditions has provided the focus of
      research over the past decades. These efforts have undoubtedly been hampered by a
      relatively poor mechanistic understanding of these processes. More recently,
      palladium-catalyzed coupling methods have led to improvements in both the
      selectivity and reliability of acetylenic homo- and heterocouplings and paved the
      way for their application to ever more complicated systems. The variety of
      acetylenic coupling protocols, the current mechanistic understanding, and their
      application in natural product and targeted synthesis are discussed
      comprehensively for the first time in this review, with an emphasis on the most
      recently developed methods, and their application to the synthesis of complex
      macromolecular structures.

PMID- 10934392
TI  - Highly Polar Metal-Metal Bonds in "Early-Late" Heterodimetallic Complexes.
AB  - Metal-metal bond polarity in its extreme form involving transition elements is
      found in di- or polynuclear complexes in which molecular fragments containing
      metal atoms from the two ends of the d block in the periodic table are combined.
      This linkage by direct metal-metal bonds of metal centers having very different
      oxidation states has been a challenge to the synthetic chemist. The suppression
      of degradative reaction channels caused by intramolecular single-electron
      transfer and the protection of the highly Lewis acidic early transition metal
      center by an appropriately designed ligand shell have opened up the systematic
      investigation of such systems. Concomitant with this development, advances in the
      conceptual framework for the quantitative description of bond polarity have led
      to a refined understanding of the nature of this type of metal-metal bonding. The
      greatest stimulus for the development of this field of research is the
      investigation of the cooperative reactivity of two or more coordination centers
      in their interaction with and transformation of organic substrates. This
      cooperativity, which is characterized by the different functions adopted by the
      metal centers in these conversions offers attractive perspectives in
      stoichiometric or even catalytic transformations.

PMID- 10934393
TI  - Two-Dimensional Crystals of Poly(3-Alkyl- thiophene)s: Direct Visualization of
      Polymer Folds in Submolecular Resolution This work was supported by the European
      Union in the framework of Frequent-Esprit 24793.

PMID- 10934394
TI  - Dioxadiazadecalin/Salen Tautomeric Macrocycles and Complexes: Prototypal Dynamic
      Combinatorial Virtual Libraries New Supramolecular Host Systems, Part 12. Part
      11: ref. 1. We gratefully acknowledge support by a research grant from the Israel
      Science Foundation and by an Intel Scholarship (to A.S.), as well as the valuable
      assistance of Shimon Hauptman with mass spectrometry and Yuri Paskover as an
      undergraduate research student.

PMID- 10934395
TI  - Lanthanide

PMID- 10934396
TI  - Selective Hydroxylation of a Steroid at C-9 by an Artificial Cytochrome P-450 We
      thank the National Institutes of Health, the National Science Foundation, and the
      Environmental Protection Agency for financial support of this research. J.Y.
      acknowledges support from an NCERQA EPA Graduate Fellowship and a Bristol-Myers
      Squibb Graduate Fellowship.

PMID- 10934397
TI  - A Porous Crystalline Molecular Solid Explored by Hyperpolarized Xenon We thank
      the Italian Ministry of Universities and Scientific Research (PRIN program) for
      financial support. The research with laser-polarized xenon was supported by the
      Director, Office of Energy Research, Office of Basic Energy Science, Materials
      Sciences Division of the U.S. Department of Energy. T.M. thanks the Alexander von
      Humboldt Foundation for a Feodor Lynen Fellowship.

PMID- 10934398
TI  - A Three-Dimensional Polyrotaxane Network This paper is dedicated to the memory of
      Professor Chung Hoe Koo, who first introduced X-ray crystallography to Korea. We
      gratefully acknowledge the Korean Ministry of Science and Technology (Creative
      Research Initiative Program) for support of this work and the Korean Ministry of
      Education (Brain Korea 21 program) for graduate studentships to E.L. and J.H.

PMID- 10934399
TI  - Ordered Hierarchical Porous Materials: Towards Tunable Size- and Shape-Selective
      Microcavities in Nanoporous Channels The Pacific Northwest National Laboratory is
      operated by Battelle for the U.S. Department of Energy under Contract DE-AC06
      76RL0 1830. This work is supported by the Office of Basic Energy Sciences,
      Division of Materials Sciences, of the U.S. Department of Energy.

PMID- 10934400
TI  - Hierarchical Pore Structures through Diatom Zeolitization We are grateful to
      BNFL, BOC, Engelhard, ICI, and EPSRC for financial support and to Richard
      Plaisted and James Forrest for providing the colloidal silicalite. We would also
      like to thank Micromeritics Ltd. for their help in obtaining the sorption and
      porosimetry data.

PMID- 10934401
TI  - Small-Molecule Inhibitors of HIV-1 Protease Dimerization Derived from Cross
      Linked Interfacial Peptides This work was supported by NIH (GM52739) and NSF
      (9457372-CHE).

PMID- 10934402
TI  - A Highly Efficient and Convergent Reaction for the Synthesis of Bridgehead Enone
      Containing Polycyclic Ring Systems Financial support from the NIH (GM59403-01A1),
      Bristol-Myers Squibb, Merck Research Laboratories, Pharmacia & Upjohn, Smith
      Kline Beecham, the Corning Fund, and the Research Corporation is gratefully
      acknowledged. G.L. acknowledges Eli Lilly for a graduate fellowship.

PMID- 10934403
TI  - Hydrogen-Bonded Molecular Ribbons as Templates for the Synthesis of Modified
      Mineral Phases This work was supported by the ICI Strategic Research Fund, the
      EPSRC, and the Wellcome Trust.

PMID- 10934404
TI  - Interanionic O-H small middle dot small middle dot small middle dotO
      Interactions: The Charge Density Point of View The Oak Ridge National Laboratory
      is managed by Lockheed Martin Energy Research Corporation for the US Department
      of Energy (DE-AC05-96OR22464). Prof. M. Moret and Dr. L. Carlucci are thanked for
      help in crystallizing large samples suitable for the neutron study. P.M.
      gratefully acknowledges DANSYNC center under the Danish Natural Science Research
      Council for a post-doctoral grant.

PMID- 10934405
TI  - A New Kinetic Template Synthesis of Triphosphacyclodecanes This work was funded
      by the EPSRC.

PMID- 10934406
TI  - Cross-Coupling Reactions between alpha,beta-Unsaturated Ketones and Aldehydes
      with CrCl(2): Aldol Condensation and Cyclopropanol Formation Financial support by
      a Grant-in-Aid for Scientific Research on Priority Area No. 706 from the Ministry
      of Education, Science, Sports and Culture of Japan is gratefully acknowledged. We
      would also like to thank Professor Ilhyong Ryu of Osaka Prefecture University for
      helpful discussions, and Dr. Teruhiko Ishikawa of Okayama University for
      conducting the NOE experiments.

PMID- 10934407
TI  - Highly 1,2-trans Stereoselective Allylations of 1,2-O-Isopropylidene-Protected
      Glycofuranosides This work was supported by the Canary Islands Consejeria de
      Educacion y Ciencia (PI1998/109), the Spanish Comision Interministerial de
      Ciencia y Tecnologia (PB98-0443-C02-02), and the FEDER (1SD97-0747-C04-01).

PMID- 10934408
TI  - A Hexagonal Perovskite Intergrowth Compound: La(2)Ca(2)MnO(7) We are thankful for
      financial support from the Youth Scientist Excellency Foundation (29625101), NSFC
      (29731010), and State Key Basic Research Program. Work performed at Argonne is
      supported by US DOE-BES under Contract No. W-31-109-ENG-38.

PMID- 10934409
TI  - Synthesis of the Kedarcidin Core Structure by a Transannular Cyclization Pathway
      Financial support from the National Institutes of Health is gratefully
      acknowledged.

PMID- 10934410
TI  - Enantioselective Generation of Benzylic Stereocenters Mediated by a Remote
      Sulfoxide This work was supported by the Direccion General de Investigacion
      Cientifica y Tecnica (Grants PB98-0062 to M.C.C. and PB98-0078 to J.L.G.R.).

PMID- 10934411
TI  - Continuous Reactions in Supercritical Water: A New Route to La(2)CuO(4) with a
      High Surface Area and Enhanced Oxygen Mobility We thank Ms. E. P. Chinennikova,
      Dr. A. Cabanas, Dr. J. A. Darr, Dr. D. A. Graham, and Mr. M. Guyler for their
      help. We are grateful to EPSRC (grant no. GR/K84929), the Royal Society, NATO,
      the Royal Academy of Engineering, and the Russian Foundation for Basic Research
      for support.

PMID- 10934412
TI  - Evidence for Dangling Bond Mediated Dimerization of Furan on the Silicon (111)
      (7x7) Surface This work was supported by the National University of Singapore
      (grant no. 3970612).

PMID- 10934413
TI  - Lord of the Rings: An Octameric Lanthanum Pyrazolonate Cluster Coordination
      Number Incommensurate Cluster Formation, Part 14. This research was supported by
      the NSF (CHE-9709621 and INT-9603212) and by NATO (SRG951516). We gratefully
      acknowledge Dr. Frederick J. Hollander for help in the crystal structure
      determination. Part 13: T. N. Parac, M. Scherer, K. N. Raymond, Angew. Chem.
      2000, 112, 1288-1291; Angew. Chem. Int. Ed. 2000, 39, 1239-1242.

PMID- 10934414
TI  - Evidence for Scattering Resonances in the H+D(2) Reaction We thank Donald G.
      Truhlar, Patrick Brown, Zee Hwan Kim, and Stephen Cho for careful and critical
      reading of the manuscript prior to publication. We also thank Andrew J. Alexander
      for his assistance in the preparation of the polar plots. Elf-Atochem (B.D.B.),
      the Hertz Foundation and Stanford University (J.D.A.), and the National Science
      Foundation (A.E.P.) are gratefully acknowledged for their support in the form of
      Graduate Fellowships. This work was supported at Stanford University by the U.S.
      National Science Foundation under Grant Number CHE-99-00305 and at Universidad
      Complutense by DGCYT PB98-0762-C03-01.

PMID- 10934415
TI  - New Chiral Auxiliaries for the Construction of Quaternary Stereocenters by Copper
      Catalyzed Michael Reactions This work was supported by the Deutsche
      Forschungsgemeinschaft and the Fonds der Chemischen Industrie. We are also
      grateful to the Degussa-Huls AG for gifts of amino acids and to Prof. Dr. S.
      Blechert for his support.

PMID- 10934416
TI  - Detection of a 2,3-Aminomutase in the Mushroom Cortinarius violaceus This
      contribution was supported by the Deutsche Forschungsgemeinschaft (SFB 369).

PMID- 10934417
TI  - Demonstration of Chiral Enantiomerization in a Four-Atom Molecule This work was
      supported at Erlangen by the Deutsche Forschungsgemeinschaft and the Fond der
      Chemischen Industrie. We thank Prof. K. Mislow (Princeton) and Prof. P. Mezey
      (Saskatoon, Saskatchewan) for helpful discussions.

PMID- 10934418
TI  - 1,3-Stereoinduction in Radical Reactions.

PMID- 10934419
TI  - Carbohydrate Derivatives for Use in Drug Design: Cyclic alpha(v)-Selective RGD
      Peptides This work was supported by the Fonds der Chemischen Industrie, the
      Deutsche Forschungsgemeinschaft, and the Sanderstiftung. The authors thank M.
      Urzinger, B. Cordes, M. Kranawetter, M. Wolff, and A. Zeller for technical
      assistance.

PMID- 10934420
TI  - A Short Total Synthesis of Kuehneromycin A This work was generously supported by
      the Deutsche Forschungsgemeinschaft and the Fazit-Stiftung. We are grateful to
      Prof. W. Steglich, Ludwig-Maximilians-Universitat Munchen, for copies of spectra
      of natural kuehneromycin A and for recording 600 MHz (1)H NMR spectra of our
      synthetic sample. We thank BASF AG, Ludwigshafen, Germany, Pfizer AG, Karlsruhe,
      Germany, Haarmann & Reimer GmbH, Holzminden, Germany, Wacker GmbH, Burghausen,
      Germany, DEGUSSA AG, Frankfurt a. M., Germany and Bayer AG, Leverkusen, Germany,
      for chemicals and laboratory equipment.

PMID- 10934421
TI  - The First Low Molecular Weight Antibiotic from Lactic Acid Bacteria:
      Reutericyclin, a New Tetramic Acid.

PMID- 10934422
TI  - Synthesis of the Adduct DMAP small middle dotBrP(=N-Mes*)(2) and of the Salt

PMID- 10934423
TI  - (2,6-Mes(2)H(3)C(6))(2)BiH, a Stable, Molecular Hydride of a Main Group Element
      of the Sixth Period, and Its Conversion to the Dibismuthene (2,6
      Mes(2)H(3)C(6))BiBi(2,6-Mes(2)C(6)H(3)) This work was supported by the National
      Science Foundation. The Bruker SMART 1000 difractometer was funded in part by NSF
      Instrumentation Grant CHE-9808259. Mes=2,4,6-Me(3)C(6)H(2).

PMID- 10934424
TI  - Synthesis of (E)-alpha,beta-Unsaturated Esters and Amides with Total Selectivity
      Using Samarium Diiodide We thank the II Plan Regional de Investigacion del
      Principado de Asturias (PB-PGI99-01) and the Ministerio de Educacion y Cultura
      (PB97-1278) for financial support. J.M.C. thanks Carmen Fernandez for her help.
      H.R.S. thanks the Universidad de Oviedo for a predoctoral fellowship.

PMID- 10934426
TI  - Synthesis and Structure of the Germylyne Complexes trans-

PMID- 10934425
TI  - Investigations of Lipid-Protein Interactions on Monolayers of Chain-Substituted
      Phosphatidylcholines This work was supported by the Deutsche
      Forschungsgemeinschaft.

PMID- 10934427
TI  - Isolation of a Kinetically Stabilized 1,3,6-Triphosphafulvene This work was
      supported in part by a Grant-in-Aid for Scientific Research (No. 09239101) from
      the Ministry of Education, Science, Sports and Culture, Japan.

PMID- 10934428
TI  - Fast Photoisomerization of a Rhodopsin Model-An Ab Initio Molecular Dynamics
      Study This work was supported by the Deutsche Forschungsgemeinschaft (Graduate
      College "Struktur und Dynamikheterogener Systeme").

PMID- 10934429
TI  - Special feature on electrospray ionization

PMID- 10934430
TI  - Some tenets pertaining to electrospray ionization mass spectrometry.
AB  - The field of electrospray ionization mass spectrometry is reviewed with emphasis
      placed upon advances in the elucidation of fundamental mechanistic aspects of the
      ionization process that have been reported over the past 10 years. The analytical
      consequences of these findings are also examined. Eight central conclusions or
      'tenets' are presented, as deduced from the body of work contained in 80
      references.

PMID- 10934431
TI  - Electrolytic deposition of metals on to the high-voltage contact in an
      electrospray emitter: implications for gas-phase ion formation.
AB  - The electrospray ion source is an electrolytic flow cell. Electrolytic reactions
      in the electrospray emitter maintain the production of charged droplets by this
      ion source that contain an excess of ions of one polarity. These redox reactions
      necessarily change the composition of the solution that initially enters the
      emitter. As a result, the ions ultimately observed in the gas phase by
      electrospray mass spectrometry (ESMS) may be substantially influenced by both the
      nature and extent of these electrochemical reactions. It is demonstrated in this
      paper that Ag(+), Cu(2+) and Hg(2+) ions in solution can be electrolytically
      reduced and deposited as the respective metals on to the surface of the high
      voltage contact in the electrospray emitter in negative ion mode electrospray.
      The deposited metals are shown to be liberated from the surface by switching the
      electrospray high-voltage polarity to operate in the positive ion mode. The
      deposited metals are oxidized in positive ion mode, releasing the metal ions back
      into solution where they are detected in the electrospray mass spectrum. In a
      semi-quantitative analysis, it was found that up to 50% of the Ag(+) in a 2.5
      microM solution was deposited on the high-voltage contact of the emitter as the
      solution flowed through the emitter. Deposition of Cu(2+) and Hg(2+) was less
      efficient. These data illustrate that in the analysis of metals by ESMS, one must
      be aware that both the concentration and form of the metals may be altered by
      electrochemical processes in the emitter. Hence reduction or oxidation of metals
      in the electrospray emitter, which may remove ions from solution, or change metal
      valence, would be expected to impact both quantitative metal determinations and
      metal speciation attempts using ESMS.

PMID- 10934432
TI  - Importance of gas-phase proton affinities in determining the electrospray
      ionization response for analytes and solvents.
AB  - The effect of gas-phase proton transfer reactions on the mass spectral response
      of solvents and analytes with known gas-phase proton affinities was evaluated.
      Methanol, ethanol, propanol and water mixtures were employed to probe the effect
      of gas-phase proton transfer reactions on the abundance of protonated solvent
      ions. Ion-molecule reactions were carried out either in an atmospheric pressure
      electrospray ionization source or in the central quadrupole of a triple
      quadrupole mass spectrometer. The introduction of solvent vapor with higher gas
      phase proton affinity than the solvent being electrosprayed caused protons to
      transfer to the gas-phase solvent molecules. In mixed solvents, protonated
      solvent clusters of the solvent with higher gas-phase proton affinity dominated
      the resulting mass spectra. The effect of solvent gas-phase proton affinity on
      analyte response was also investigated, and the analyte response was suppressed
      or eliminated in solvents with gas-phase proton affinities higher than that of
      the analyte.

PMID- 10934433
TI  - Kinetics of small ion evaporation from the charge and mass distribution of
      multiply charged clusters in electrosprays
AB  - The distribution of charge z and radii R in clusters electrosprayed from
      formamide solutions of tetraheptylammonium bromide was investigated by selecting
      those within a narrow range of electrical mobilities Z(1) in a first differential
      mobility analyzer (DMA), reducing their charge to unity by passage through a
      neutralizing chamber containing a radioactive (alpha) source, and measuring the
      mobilities Z(z) of the resulting discrete set of singly charged clusters in a
      second DMA. After correcting for the polarization contribution to cluster drag,
      the tandem DMA data yield the range of radii present at detectable levels for
      each charge state up to z = 9. Because small ion evaporation from electrospray
      drops leads to charge loss when a drop reaches a certain critical radius
      R(crit)(z), the measured maximum and minimum cluster radii associated with a
      given z can be used to infer the activation energy Delta for ion evaporation as a
      function of drop charge and curvature. These results confirm the Iribarne-Thomson
      ion-evaporation mechanism, and support earlier theoretical expressions for the
      functional form of Delta(z,R). The different phenomenon of ion evaporation from
      metastable multiply charged dry clusters is also observed at characteristic times
      of 1 s. Its activation energy is estimated as approximately 0.3 eV larger than
      for ion evaporation from the drops. This new process complicates the
      interpretation of the present measurements in terms of ion evaporation from
      liquid surfaces, but introduces no radical change in the picture. It helps
      understand why salt clusters with more than two or three charges are harder to
      see in mass spectrometers than in mobility studies under ambient conditions.
      Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10934435
TI  - Mass spectrometric study of persistent acid metabolites of nonylphenol ethoxylate
      surfactants.
AB  - A mass spectrometric study was carried out on two nonylphenoxycarboxylic acids,
      NP1EC and NP2EC (where 1 and 2 indicate the number of ethoxylate units attached
      to the nonylphenoxy moiety), that are persistent metabolites of widely used
      nonionic surfactant nonylphenol ethoxylates. In a gas chromatographic/mass
      spectrometric (GC/MS) study of the methyl esters of NP1EC and NP2EC, two series
      of fragment ions were observed in electron ionization (EI) mass spectra; m/z (179
      + 14n, n = 0-7) and m/z (105 + 14n, n = 0-4) for NP1ECMe and m/z (223 + 14n, n =
      0-7) and m/z (107 + 14n, n = 0-5) for NP2ECMe. Similarity indices were used to
      compare quantitatively the mass spectra of isomers. The mass spectra of two
      isomers were found to be similar whereas those of the remaining isomers were
      readily distinguishable from each other. The abundant fragment ions of the two
      NPECMes were investigated further by GC/MS/MS; product ions resulting from
      cleavage in the alkyl moiety, cleavage in the ECMe moiety and cleavage in both
      moieties were detected. Possible structures of the nonyl groups in the two esters
      were inferred. GC/chemical ionization (CI) mass spectra of the NPECMes with
      isobutane as reagent gas showed characteristic hydride ion-abstracted fragment
      ions shifted by 1 Da from those in the corresponding EI mass spectra. The
      sensitivity of a selected ion monitoring quantitation method for the NPECMes is
      enhanced under CI conditions compared with that under EI conditions. With
      electrospray ionization MS/MS, [M - H](-) ions of NP1EC (m/z 277) and NP2EC (m/z
      321) were observed and, upon collision-induced dissociation of [M - H](-) of each
      of the two acids, fragment ions of m/z 219 corresponding to deprotonated
      nonylphenol, were observed in each case. Based on this observation, a rapid,
      simple and reliable selected product ion quantitation method is proposed for
      NP1EC and NP2EC.

PMID- 10934436
TI  - Structural analysis of (methyl-esterified) oligogalacturonides using post-source
      decay matrix-assisted laser desorption/ionization time-of-flight mass
      spectrometry.
AB  - The use of post-source decay matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry for the structural analysis of ((partly) methyl
      esterified) oligogalacturonides (oligoGalA) is described. The fragmentation
      behavior of purified (un)saturated oligoGalA (degree of polymerization 3-6),
      methyl-esterified and methyl-glycosydated oligoGalA was studied. General
      fragmentation patterns are described and used for the elucidation of the
      positions of methyl esters on partly methyl-esterified oligoGalA. This technique
      now permits the determination of the position of methyl esters or other
      substituents on pectic fragments, helping in understanding the mode of action of
      pectinolytic enzymes.

PMID- 10934437
TI  - Mass spectral fragmentation pathways in cyclic difluoramino and nitro compounds
AB  - The recently synthesized compounds 4, 4-bis(difluoramino)-1-nitropiperidine (I),
      1,4,4-trinitropiperidine (II), 1,1,4,4-tetranitrocyclohexane (III), 1,1,4, 4
      tetrakis(difluoramino)cyclohexane (IV) and 3,3,7, 7-tetrakis(difluora
      mino)octahydro-1,5-dinitro-1,5-diazocine (HNFX, V) are being considered as
      potential energetic materials. The mass spectra of these compounds were studied
      using electron ionization (EI) mass spectrometry. A collision-induced
      dissociation (CID) study of the major EI peaks was carried out using a Finnigan
      TSQ 700 tandem mass spectrometer. The mass fragmentation pathways are constructed
      and discussed. The decomposition of HNFX (V), under EI, appeared to parallel the
      thermal decomposition of nitramines where N-NO(2) cleavage is often the first
      step. However, the two nitramines with a six-membered ring structure (I and II)
      underwent initial loss of a geminal substituent; loss of a nitramine nitro group
      was the secondary step. The two cyclohexane structures (III and IV) showed
      similar initial fragmentation pathways, featuring successive losses of nitro or
      difluoramino groups. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10934438
TI  - Characterization of silica dissolved in sodium chloride solution using fast atom
      bombardment mass spectrometry
AB  - The chemical species of silica dissolved in sodium chloride (NaCl) solution were
      identified by means of fast atom bombardment mass spectrometry (negative ion
      mode). The concentration of silica in 0.1 M NaCl solution is < 0.6 mmol dm(-3)
      (mM) and application to the identification of the silicate species at low
      concentrations such as in natural waters level is also possible. An apparent peak
      at m/z 95, which corresponds to SiO(OH)(3)(-) in 0.1 M NaCl solution, was not
      confirmed owing to the interference of the peaks corresponding to NaCl(2)(-);
      however, peaks for complexes such as Si(OH)(2)O(2)Na(-), Si(2)(OH)(5)O(2)(-),
      Si(2)(OH)(4)O(3)Na(-), Si(2)(OH)(3)O(4)Na(2)(-), Si(2)(OH)(2)O(5)Na(3)(-),
      Si(4)(OH)(7)O(5)(-), Si(4)(OH)(6)O(6)Na(-) and Si(4)(OH)(5)O(7)Na(2)(-) were
      detected. The existence of the trimer and its Na(+) complexes such as
      Si(3)(OH)(7)O(3)(-), Si(3)(OH)(6)O(4)Na(-) and Si(3)(OH)(5)O(5)Na(2)(-) was not
      clearly shown. These complexes can be confirmed not only in the form of the anion
      itself (e.g. Si(2)(OH)(5)O(2)(-)), but also in the form of some complexes with
      sodium ions, such as Si(2)(OH)(4)O(2)Na(-). Copyright 2000 John Wiley & Sons,
      Ltd.

PMID- 10934434
TI  - A brief overview of the present status of the mechanisms involved in electrospray
      mass spectrometry.
AB  - A brief account of the mechanisms by which ions in solution are converted to ions
      in the gas phase is given on the basis of information available in the literature
      and the four companion articles on electrospray mass spectrometry (ESMS) in this
      issue. The following stages/phenomena are described: (a) production of the
      charged droplets at the ES capillary tip; (b) evolution of the charged droplets
      due to solvent evaporation and droplet fission caused by Coulombic repulsion of
      the charges on the droplets; production of the gas phase ion from very small
      charged droplets by the charge residue model (CRM) or the ion evaporation method
      (IEM); (c) dependence of the sensitivity in ESMS on the chemical nature of the
      analyte and its concentration as well as on the concentration of other
      electrolytes that are present in the solution; qualitative predictions on the
      sensitivity of the analyte based on the surface activity of the analyte ions; (d)
      relationship between ions produced in the gas phase and original ions present in
      the solution; and (e) globular proteins. Much of the information presented in (a)
      (e) has been available for some time in the literature. However some significant
      advances are relatively recent. Recent results by de la Mora and co-workers,
      including their contribution in this Special Feature, provide very strong
      evidence that small ions (in distinction from macroions such as bio-macroions)
      are produced by IEM. On the other hand, macroions and particularly the
      polyprotonated globular proteins are produced by CRM. Also noteworthy is the
      development of an equation by Enke with which the observed relative ion signal
      intensities of the gas-phase ions produced can be predicted on the basis of the
      ion concentration in solution over a wide concentration range. The recognition
      that the sensitivity of organic analyte ions can be qualitatively predicted on
      the basis of the hydrophilicity or hydrophobicity of the part of the molecule
      that is not part of the charged (ionic) group and affects the surface activity of
      the ionic species is also noteworthy and a very useful relatively recent
      development.

PMID- 10934440
TI  - Comparison of direct infusion and on-line liquid chromatography/electrospray
      ionization mass spectrometry for the analysis of nucleic acids.
AB  - The applicability of ion-pair reversed-phase high-performance liquid
      chromatography/electrospray ionization mass spectrometry (IP-RP-HPLC/ESI-MS) and
      direct infusion/ESI-MS to the characterization of nucleic acid mixtures was
      evaluated by the analysis of the reaction products obtained from solid-phase
      synthesis of a 39-mer oligonucleotide. IP-RP-HPLC/ESI-MS was performed using 200
      microm i.d. capillary columns packed with octadecylated, micropellicular
      poly(styrene-divinylbenzene) particles and applying gradients of acetonitrile in
      50 mM triethylammonium bicarbonate (TEAB). Three different solvent systems were
      utilized for direct infusion/ESI-MS with removal of metal cations by on-line
      cation exchange: (1) 10 mM triethylamine (TEA) in 50% aqueous acetonitrile, (2)
      2.2 mM TEA, 400 mM hexafluoro-2-propanol (HFIP) in 20% aqueous methanol and (3)
      50 mM TEAB in 10% aqueous acetonitrile. Owing to its separation capability, the
      highest selectivity and specificity were achieved with IP-RP-HPLC/ESI-MS, which,
      apart form the 39-mer target sequence, allowed the identification of two
      isobutyryl-protected target sequences and a 10-mer and 20-mer failure sequence.
      Direct infusion/ESI-MS with TEA-acetonitrile or TEA-HFIP-methanol as solvent
      revealed signals for the 39-mer in the m/z range 700-1600. The presence of
      derivatives containing one, two, three and four isobutyryl groups indicated that
      the hydrolysis of the protecting groups after solid-phase synthesis was not
      complete. Failure sequences could not be identified by direct infusion/ESI-MS
      under conditions favoring multiple charging of the analytes owing to the high
      chemical background and coincidental overlapping of m/z signals. However,
      efficient charge state reduction upon addition of carbonic acid to the
      electrosprayed solvent shifted the signals of the 39-mer and derivatives to m/z
      values >2400 and allowed the detection of seven different failure sequences,
      ranging from the 8-mer to the 23-mer, in the mixture.

PMID- 10934439
TI  - Tandem mass spectrometry studies of green tea catechins. Identification of three
      minor components in the polyphenolic extract of green tea.
AB  - Liquid chromatography/electrospray ionization mass and tandem mass spectrometry
      (MS/MS) techniques were used to identify two minor components and one new
      compound in the polyphenolic extract of green tea (Camellia sinensis).
      Identification and structure assignments were based on previously reported sub
      structural features in the MS/MS product, precursor and neutral loss scans of
      reference samples. The structures of two minor components, related to the known
      green tea components epicatechin gallate (ECG, 5) and epigallocatechin gallate
      (EGCG, 6), are formed by methylation at the 3"-O-position of the gallic acid
      moiety. The new compound contained a gallic acid ester group, but had only one
      phenolic group in either the A- or B-ring, relative to the structure of 5. High
      resolution mass measurements supported the empirical formula assigned to the new
      compounds. An important fragmentation for defining the position of methylation of
      the ester function involves ionization of the phenolic group at the 4"-position
      of the gallic acid, followed by elimination of the ester function as a neutral
      with concomitant formation of the m/z 169 ion. If the 4"-position is blocked by
      methylation, the formation of m/z 169 incorporating the gallic acid group would
      be blocked. Thus, the presence of an ion representing the ester group indicates a
      free 4"-phenol and the absence of this ion would signify the 4"-position as a
      site of methylation. The operation of this mechanism should be general and useful
      in assigning the site of methylation of any polyphenolic ester group in natural
      products. A similar conclusion can be drawn concerning alkylation or
      esterification of the 4'-position of the catechins, i. e. blocking the 4'-phenol
      would prevent formation of the m/z 125 ion common to all of the catechin
      compounds thus far examined. Therefore, mass spectral data are of considerable
      importance in deducing the sites of alkylation or esterification in the
      structures of the components of green tea.

PMID- 10934441
TI  - Selenium speciation in animal tissues after enzymatic digestion by high
      performance liquid chromatography coupled to inductively coupled plasma mass
      spectrometry.
AB  - A procedure is described for the enzymatic digestion of tuna and mussel samples
      that allows the determination of selenium species by high-performance liquid
      chromatography in conjunction with inductively coupled plasma mass spectrometry.
      The species were extracted by two-step enzymatic hydrolysis with a non-specific
      protease (subtilisin). The selenium species were separated on a Spherisorb 5
      ODS/AMINO column using two different chromatographic conditions, namely phosphate
      buffers at pH 2.8 and pH 6.0 as mobile phases. The method determines organic
      (trimethylselenonium, selenocystine, selenomethionine and selenoethionine) and
      inorganic selenium species (selenite and selenate), but only organic selenium
      species were found in the samples. The sum of identified selenium species in the
      sample was about 30% of the total selenium present in the enzymatic extract
      despite the fact that recoveries of total hydrolysed selenium were 93-102%.
      Trimethylselenonium ion and selenomethionine were found in both tuna and mussel
      samples and an unknown selenium species was also found in tuna samples.

PMID- 10934442
TI  - Tandem mass spectrometric study of 1,3,5-trinitrobenzene molecular ion: an
      unusual ortho effect involving a hydrogen atom from the aromatic ring
AB  - Unimolecular (metastable) and collision-induced dissociation of 1,3, 5
      trinitrobenzene molecular ion was studied using linked scans and mass-analyzed
      ion kinetic energy spectrometry on a hybrid instrument of EBEqQ geometry. An
      unusual ortho effect leading to the loss of OH radical from the parent molecular
      ion is observed as a unimolecular dissociation process only in the first-field
      free region between the ion source and the electric sector, although
      corresponding dissociation in the ion source is of negligible abundance (<0.1%).
      This unimolecular process is taken over by other dissociation pathways when the
      parent ion is collisionally activated, suggesting that this dissociation process
      occurs only in a very narrow energy window with a rate constant of the order of 2
      x 10(5) s(-1). Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10934443
TI  - Modification of capillaries coupled to micro-flow nebulizers: a new strategy for
      on-line interference removal in inductively coupled plasma mass spectrometry.
AB  - The application of interference removal within modified silica capillaries for
      the introduction of liquid samples by a micro-flow nebulizer into an inductively
      coupled plasma quadrupole mass spectrometer is described using the example of
      (103)Rh and its mass interferences resulting from (63)Cu (ArCu(+)), (87)Rb
      (RbO(+)), (87)Sr (SrO(+)) and (206)Pb (Pb(2+)). A strong cation exchanger was
      covalently bound to the capillary surface and its ability to interact with
      cations in aqueous solution was investigated. At pH 7. 0 the interfering elements
      can be selectively adsorbed within the capillaries without hampering the elution
      of Rh. The capillaries are easily regenerated by flushing with 10(-3) M
      hydrochloric acid in order to exchange retained cations for protons. Calibrations
      show no significant difference between the absence and presence of interfering
      elements, so the detection limit for Rh of 6.0 ng l(-1) (3sigma) is not
      influenced by adding up to a 100-fold excess of interferents. The method
      developed is compared with a mathematical correction model for inductively
      coupled plasma mass spectrometry using the example of Rh determination in
      particulate car exhaust fumes and the results obtained are discussed.

PMID- 10934444
TI  - Liquid secondary ion mass spectrometric investigation of ion-pair precipitates of
      some ethoxylates with barium tetraphenylborate
AB  - Liquid secondary ion mass spectrometry seems to be useful technique for the
      qualitative characterization of ion-pair precipitates of ethoxylates with barium
      tetraphenylborate. In the positive mode, barium complexes of ethoxylates were
      examined. In the negative mode, the ion signal of tetraphenylborate had 100%
      intensity relative to the matrix peaks. The low-resolution mass spectra were
      found to be suitable for checking the purity of ion-pair precipitates of
      ethoxylates with barium tetraphenylborate. On the basis of B/E mass spectra, the
      fragmentation routes of [M - H + Ba](+) ions are proposed. Copyright 2000 John
      Wiley & Sons, Ltd.

PMID- 10934445
TI  - Effect of metal cationization on the low-energy collision-induced dissociation of
      loganin, epi-loganin and ketologanin studied by electrospray ionization tandem
      mass spectrometry
AB  - The effect of alkali metal and silver cationization on the collision-induced
      dissociation (CID) of loganin (1), epi-loganin (2) and ketologanin (3) is
      discussed. Their protonated molecular ions fragment mainly by glycosidic
      cleavages. The epimeric pairs (1 and 2) show differences in the abundances of the
      resulting fragment ions. Lithium cationization induces new dissociation pathways
      such as the retro-Diels-Alder (RDA) fragmentation followed by rearrangement.
      Unlike the dissociation of protonated molecular ions, the dissociation of
      lithiated molecules also provides lithiated sugar fragments. The CID of
      dilithiated molecules is substantially different from that of the monolithiated
      precursors. RDA reaction appears to be favoured by the presence of the additional
      lithium atom in the molecule. In addition, other ring cleavages are also induced.
      The abundances of the various fragment ions are different in the CID spectra of
      the epimeric pairs. Extensive D labelling and (6)Li labelling experiments
      confirmed many of the ion structures proposed. The CID spectra of the sodiated
      ions are generally weaker, although similar to those of the corresponding
      lithiated species. Higher alkali metal ion (K(+), Rb(+) and Cs(+)) adducts
      generated only the corresponding metal ions as products of CID. Similar
      fragmentations were also observed in the CID of the [M + Ag](+) ions of these
      compounds, the epimeric pairs showing characteristic differences in their CID
      behaviour. Copyright 2000 John Wiley & Sons, Ltd.

PMID- 10934446
TI  - Automated liquid chromatographic/tandem mass spectrometric method for screening
      beta-blocking drugs in urine.
AB  - An automated liquid chromatographic/tandem mass spectrometric (LC/MS/MS) method
      is presented for the screening and confirmation of 16 beta-blocking drugs in
      clinical and autopsy urine samples. The described method involved C(18) solid
      phase extraction, LC separation and MS analysis on a triple-stage quadrupole mass
      analyser. Samples were initially pre-screened for the presence of any beta
      blocking drugs using LC/MS with selected ion monitoring. Any compounds
      tentatively identified as beta-blocking drugs on the basis of their LC retention
      time and protonated molecular ion were then automatedly subjected to a second
      analysis in which the relevant MS/MS product ion mass spectra were acquired.
      These product ion mass spectra were then automatically searched against a 400
      substance mass spectral library containing previously acquired beta-blocking
      drugs. The results demonstrated that library search of beta-blocking drugs in
      urine with MS/MS product ion mass spectra was more reliable and produced fewer
      false negatives than library searching with mass spectra derived from single
      stage quadrupole MS. The limits of identification in the MS/MS product ion scan
      ranged from 0.02 mg l(-1) for carvedilol to 1.2 mg l(-1) for pindolol, the
      majority of the values being below 0.2 mg l(-1).

PMID- 10934447
TI  - Optimization of capillary electrophoresis conditions for coupling to a mass
      spectrometer via a sheathless interface.
AB  - When optimizing a capillary electrophoresis/electrospray ionization mass
      spectrometry (CE/ESI-MS) system, consideration has to be given not only to the
      separation but also to the electrospray stability. Methods developed for CE/UV
      analysis of drugs and peptides were considered and modified to be suitable for a
      CE/MS system with a robust sheathless interface. Different concentrations of the
      organic modifiers acetonitrile, methanol and 2-propanol were used in the
      separation buffer. The type and concentrations of these modifiers were also
      compared with reference to electrospray stability, sensitivity and time of
      analysis. In addition, different ionic strengths in the buffers were evaluated
      with reference to electrospray stability. The repeatability was used for the
      estimation of electrospray stability. The degree to which these parameters
      influenced the separation and the ESI stability was studied using a nine-peptide
      standard mixture and the antibiotic drugs bacampicillin and ampicillin as test
      substances. The analysis time and resolution were used as measures of the
      efficiency of the separation. A time-of-flight MS analyzer was used since it has
      the potential advantages of becoming a better fit for integration of CE with MS
      owing to the speed and sensitivity of this mass analyzer. The detection limit,
      i.e. 1 microM, for bacampicillin was comparable to what could be achieved with
      CE/MS on a quadrupole instrument using selected ion monitoring and sheath flow
      ESI.

PMID- 10934448
TI  - Current awareness.
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books,
      Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion
      Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins;
      Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural
      Products; 7 Analysis of Organic Compounds; 8 Analysis of
      Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11
      Elemental Analysis. Within each section, articles are listed in alphabetical
      order with respect to author (5 Weeks journals - Search completed at 27th. Apr
      2000)

PMID- 10934449
TI  - In this issue

PMID- 10934450
TI  - Widening awareness of hyperglycemia unawareness.
AB  - Hyperglycemia unawareness is the term suggested to me (M. Muggeo, personal
      communication, 1997) to encompass very broadly all of the stages in diabetes
      mellitus from the onset of any degree of hyperglycemia until the diagnosis is
      actually made. Diabetes and its handmaiden, obesity, are growing in epidemic
      proportions in the US and worldwide. In contrast to obesity where the diagnosis
      is recognized quite early by the patient, the family and the physician, the
      diagnosis of diabetes may be delayed from 5 to 15 years after its onset1-5. A
      significant minority of adults, when newly diagnosed with Type 2 diabetes, have
      definable evidence of macrovascular or microvascular complications. Presumably
      those same individuals, were we able to examine their cells and organs, would
      show additional evidence of the complications of diabetes. Likewise, with the
      recognition that hyperglycemia per se is a very powerful determinant of the
      complications of diabetes, we suspect that even those people with the delayed
      recognition of hyperglycemia but without evidence of complications at the time of
      diagnosis already have sustained some of the underlying damage typical of
      diabetic complications. This is supported by the finding that in this group of
      patients, there are those who will have an 'accelerated rate' of onset of
      diabetic complications2 (relative to patients with Type 1 diabetes where the
      onset of hyperglycemia is very close to the time of the diagnosis). Our
      interpretation is that the progress of the disease may not really be especially
      rapid; rather, the dating of the onset has been incorrect.

PMID- 10934451
TI  - Early detection of undiagnosed diabetes mellitus: a US perspective.
AB  - Undiagnosed Type 2 diabetes has become a common condition in the US, comprising
      one-third of all cases of the disease. We believe that screening for and
      detection of undiagnosed Type 2 diabetes is an important endeavor. In this review
      we provide evidence that diabetes is a condition that is appropriate for
      population screening and detection. This includes evidence that: 1. Type 2
      diabetes is a significant health problem. It affects more than 16 million adults
      in the US and places these individuals at high risk for serious complications of
      the eyes, nerves, kidneys, and cardiovascular system. 2. There is a latent phase
      before diagnosis of Type 2 diabetes. During this period of undiagnosed disease,
      risk factors for diabetic micro- and macrovascular complications are markedly
      elevated and diabetic complications are developing. 3. Diagnostic criteria for
      diabetes have been established and are based on plasma glucose values. These
      criteria define a group of individuals with significant hyperglycemia who also
      have a high frequency of risk factors for micro- and macrovascular disease. 4.
      The natural history of Type 2 diabetes is understood. In most patients, diabetes
      proceeds inexorably from genetic predisposition, through the stage of insulin
      resistance and hyperinsulinemia, to beta cell failure and overt clinical disease.
      5. There are effective and acceptable therapies available for Type 2 diabetes and
      its complications. Treating hyperglycemia to prevent complications is more
      effective than treating these complications after they have developed.
      Furthermore, guidelines for treatment to prevent cardiovascular disease in people
      known to have diabetes are more stringent than in those individuals who are not
      known to have diabetes. 6. There is a suitable test for screening for undiagnosed
      Type 2 diabetes that has high sensitivity and specificity - measurement of
      fasting plasma glucose. Guidelines for identifying persons at high risk for
      diabetes have been established.

PMID- 10934452
TI  - Reverse cholesterol transport in diabetes mellitus.
AB  - There are epidemiological data and experimental animal models relating the
      development of premature atherosclerosis with defects of the reverse cholesterol
      transport (RCT) system. In this regard, the plasma concentrations of the high
      density lipoprotein (HDL) subfractions, of cholesteryl ester transfer protein
      (CETP), as well as the activity of the enzyme lecithin-cholesterol acyl
      transferase (LCAT) play critical roles. However, there has been plenty of
      evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater
      arterial wall cell uptake of modified apoB-containing lipoproteins whereas a
      primary or predominant defect of the RCT system is still a subject of debate. In
      other words, in spite of the fact that in DM the composition and rates of
      metabolism of the HDL particles are greatly altered and display a diminished in
      vitro efficiency to remove cell cholesterol, definitive in vivo demonstration of
      the importance of this fact in atherogenesis is lacking. Furthermore, the roles
      played by LCAT and CETP in RCT in DM are difficult to interpret because the in
      vitro procedures of measurement utilized have either been inadequate, or
      inappropriately interpreted. Knock-out or transgenic mice are much needed models
      to investigate the roles of LCAT, CETP, phospholipid transfer protein (PLTP), and
      of a CETP inhibitor in the development of atherosclerosis of experimental DM.

PMID- 10934453
TI  - Beta cell destruction in the development of autoimmune diabetes in the non-obese
      diabetic (NOD) mouse.
AB  - In the non-obese diabetic (NOD) mouse model of Type 1 (insulin-dependent)
      diabetes, evidence suggests that pancreatic beta cells are destroyed in part by
      apoptotic mechanisms. The precise mechanisms of beta cell destruction leading to
      diabetes remain unclear. The NOD mouse has been studied to gain insight into the
      cellular and molecular mediators of beta cell death, which are discussed in this
      review. Perforin, secreted by CD8(+) T cells, remains one of the only molecules
      confirmed to be implicated in beta cell death in the NOD mouse. There are many
      other molecules, including Fas ligand and cytokines such as interferon-gamma,
      interleukin-1 and tumor necrosis factor-alpha, which may lead to beta cell
      destruction either directly or indirectly via regulation of toxic molecules such
      as nitric oxide. As beta cell death can occur in the absence of perforin, these
      other factors, in addition to other as yet unidentified factors, may be important
      in the development of diabetes. Effective protection of NOD mice from beta cell
      destruction may therefore require inhibition of multiple effector mechanisms.

PMID- 10934454
TI  - Symptomatic and counterregulatory hormonal responses to acute hypoglycaemia
      induced by insulin aspart and soluble human insulin in Type 1 diabetes.
AB  - BACKGROUND: The aim of this study was to assess hypoglycaemia awareness with the
      insulin analogue, insulin aspart. The counterregulatory hormonal and symptomatic
      responses to hypoglycaemia induced by insulin aspart were compared with soluble
      human insulin in a double-blind, randomised, two-period crossover trial in
      patients with Type 1 diabetes. The primary objective was to compare the blood
      glucose threshold for autonomic activation during hypoglycaemia induced by
      insulin aspart and soluble human insulin. Secondary objectives were to compare
      the counterregulatory, symptomatic and physiological responses to hypoglycaemia.
      METHODS: 20 patients were screened, 17 were randomised and 16 completed the
      study. Acute hypoglycaemia was induced by intravenous infusion of insulin aspart
      or soluble human insulin (100 U ml(-1) at a rate of 2 mU kg(-1) min(-1)).
      RESULTS: No statistical difference between insulin aspart and soluble human
      insulin was shown for the primary blood glucose endpoint; mean arterialised blood
      glucose concentrations (+/-SD) at the onset of autonomic activation were 1. 88+/
      0.39 mmol L(-1) for insulin aspart and 1.89+/-0.43 mmol L(-1) for soluble human
      insulin (not significant). No statistical differences were observed between the
      two insulins for the secondary endpoints: counterregulatory hormonal responses,
      autonomic responses, hypoglycaemia symptom scores, cognitive function and blood
      glucose responses. No serious adverse events were reported during the study.
      CONCLUSIONS: Insulin aspart and soluble human insulin elicit the same
      counterregulatory and symptomatic responses to acute hypoglycaemia in patients
      with Type 1 diabetes.

PMID- 10934455
TI  - Metabolic characteristics and urine albumin excretion rate in relation to
      pubertal maturation in Type 1 diabetes.
AB  - BACKGROUND: The objective of this study was to assess the impact of pubertal
      maturation on urinary albumin excretion rate (AER) and persistent
      microalbuminuria, and to identify possible factors affecting urinary AER in
      adolescents with Type 1 diabetes. METHODS: One hundred patients aged 9.1-19.0
      years with a duration of diabetes of >2 years out of 138 eligible adolescents
      with Type 1 diabetes from an outpatient diabetes clinic participated in the
      study, together with 100 healthy controls. A timed overnight urine sample was
      collected in the hospital, where all the adolescents stayed for 22-24 h, and
      microalbuminuria was confirmed with at least one consecutive positive sample (AER
      20-200 microg/min). RESULTS: The prevalence of persistent microalbuminuria was
      6%. All the patients affected were girls: one prepubertal (T I), one in late
      puberty (T IV) and three postpubertal (T V). These patients had significantly
      higher HbA(1c) levels than did the normoalbuminuric girls with Type 1 diabetes.
      Neither duration of diabetes nor age differed significantly between the two
      groups. AER increased more conspicuously with pubertal maturation in the boys
      with Type 1 diabetes than in the control boys, while the girls with diabetes had
      significantly higher body mass index (BMI) and serum total and LDL cholesterol
      than did the control girls. HbA(1c) was independently associated with AER in a
      multiple regression model. Diastolic blood pressure (BP) was elevated in both
      girls and boys with Type 1 diabetes as compared with healthy adolescents, while
      no difference was observed between the patients with microalbuminuria and
      normoalbuminuria. CONCLUSIONS: Persistent microalbuminuria was mainly observed in
      late puberty and after puberty among adolescents with Type 1 diabetes. Female sex
      and poor metabolic control predispose such adolescents to this condition during
      pubertal maturation.

PMID- 10934456
TI  - Family association studies of markers on chromosome 2q and Type 1 diabetes in
      subjects from South India.
AB  - BACKGROUND: Several Type 1 diabetes susceptibility loci have been located to
      chromosome 2q12-21. However, results have not always been consistent and this may
      reflect study design and the population analysed. We have used a family-based
      design to look for an association between Type 1 diabetes and markers located to
      2q12-21. METHODS: Ninety-one South Indian families consisting of subjects with
      Type 1 diabetes and their parents were genotyped for eight polymorphic markers
      localised to 2q12-21, which includes the interleukin-1 gene cluster. Radiation
      hybrid mapping was used to localise the map position of D2S308 and D2S363 on 2q12
      21. The extended transmission disequilibrium test was used for statistical
      analysis. RESULTS: No associations were found between Type 1 diabetes and markers
      located in and around the interleukin-1 gene cluster or the interleukin-1 Type 1
      receptor. In contrast, a suggestive association was found between Type 1 diabetes
      and two closely-linked markers telomeric of the interleukin-1 gene cluster
      (D2S308 and D2S363, separated by 3.3 cR) (p=0.004 and p=0.002, respectively).
      CONCLUSION: This preliminary study suggests that a locus close to D2S308 and
      D2S363 is involved in the aetiology of Type 1 diabetes in the South Indian
      population.

PMID- 10934458
TI  - Fears and phobias in people with diabetes.
AB  - Phobic disorders are more common in people with diabetes than in the general
      population. The management of phobic disorders in patients with diabetes,
      particularly when associated with a fear of hypoglycaemia, is especially
      challenging and requires close collaboration between psychological medicine and
      diabetes teams. Difficulty in distinguishing symptoms of anxiety from those of
      hypoglycaemia, and the real dangers associated with hypoglycaemia, complicate the
      delivery of psychological interventions that are used routinely in the treatment
      of phobias. Avoidance of hypoglycaemia can lead to deterioration in diabetes
      control. This case report describes a man with Type 1 diabetes who developed
      agoraphobia with panic disorder, associated with fear of hypoglycaemia and
      deterioration in glycaemic control. The management of patients with diabetes and
      phobic disorders, with particular reference to those associated with fear of
      hypoglycaemia, is discussed.

PMID- 10934459
TI  - Current awareness
AB  - In order to keep subscribers up-to-date with the latest developments in their
      field, John Wiley & Sons are providing a current awareness service in each issue
      of the journal. The bibliography contains newly published material in the field
      of diabetes/metabolism. Each bibliography is divided into 17 sections: 1 Books,
      Reviews & Symposia; 2 General; 3 Genetics; 4 Epidemiology; 5 Immunology; 6
      Prediction; 7 Prevention; 8 Intervention: a&rpar General; b&rpar Pharmacology; 9
      Pathology: a&rpar General; b&rpar Cardiovascular; c&rpar Neurological; d&rpar
      Renal; 10 Endocrinology & Metabolism; 11 Nutrition; 12 Animal Studies; 13
      Techniques. Within each section, articles are listed in alphabetical order with
      respect to author (8 Weeks journals - Search completed at 19th Apr. 2000)

PMID- 10934457
TI  - Effects of prolonged exposure to pancreatic glucagon on the function,
      antigenicity and survival of isolated human islets.
AB  - BACKGROUND: Certain clinical conditions are associated with inappropriately high
      levels of circulating glucagon. To date, little information is available about
      the direct effects of prolonged exposure of human islet cells to pancreatic
      glucagon. In the present study we evaluated the function, antigenicity and
      survival of human islets exposed for 24 h to human pancreatic glucagon. METHODS:
      We prepared human islets of Langerhans by collagenase digestion and density
      gradient purification, incubated them for 24 h with 44 or 430 pmol/l pancreatic
      glucagon at physiological (5.5 mmol/l) glucose level, and evaluated their insulin
      release function, which was then compared with that obtained from islets kept at
      high (11.1 mmol/l) glucose concentration. In addition, aliquots of the islets
      were evaluated to assess their chemotactic properties towards human monocyte
      macrophage cells, and their potency to induce cytokine release from human
      lymphocytes. Finally, survival of the islet cells cultured under varying
      conditions was evaluated, and an assessment was performed of mRNA expression of
      Bcl-2 and Bax proteins. RESULTS: The insulin secretion results demonstrated that,
      compared to the control islets, the islets previously exposed to either 44 or 430
      pmol/l glucagon exhibited changes in insulin release in response to glucose,
      consisting of augmented secretion at low glucose challenge, and no further
      significant increase at high glucose stimulation, similar to the effects observed
      with islets pre-cultured with high glucose. These effects were reversible, as
      documented by the recovery of normal islet sensitivity to glucose after an
      additional 24-h culture in medium lacking glucagon. Compared to control islets,
      the culture medium from islets pre-cultured with high glucagon or high glucose
      showed an increased chemotactic potency towards human monocyte-macrophage cells.
      In addition, human lymphocytes released a greater amount of tumour necrosis
      factor alpha when co-cultured with the islets pre-exposed to high glucagon or
      high glucose, whereas no significant difference was observed (in comparison with
      control islets) as regards the release of gamma-interferon, interleukin-2 and
      interleukin-10. The TUNEL technique and RT-PCR showed, respectively, no major
      difference in cell survival and expression of mRNA encoding for Bcl-2 and Bax
      protein between control islets and islets kept for 24 h in the presence of high
      glucagon or high glucose. CONCLUSIONS: Our results show that in vitro exposure of
      human islets to pancreatic glucagon for 24 h causes changes in the function and
      antigenicity of isolated human islets that are similar to the changes observed
      after pre-culture with increased glucose levels. Under our experimental
      conditions, these changes were not accompanied by any evidence of cytotoxicity.

PMID- 10934460
TI  - The Houston Vision Assessment Test (HVAT): an assessment of validity. The
      Cataract Outcome Study Group.
AB  - PURPOSE: Cataract surgery is one of the most successful procedures in medicine,
      and outcome is typically measured by a single factor - improvement in visual
      acuity. Health-related functional outcome testing, which quantifies the patient's
      self-reported perception of impairment, can be integrated with objective clinical
      findings. Based on the patient's self-assessed lifestyle impairment, the
      physician and patient together can make an informed decision on the treatment
      that is most likely to benefit the patient. METHOD: A functional outcome test
      (the Houston Vision Assessment Test - HVAT, copyrighted 1990, 1992) was evaluated
      in a cataract population of 149 patients from seven study centers. Test results
      were correlated with objective ophthalmic endpoints. The HVAT divides an
      estimated total impairment into subcomponents of Visual Impairment (correctable
      by cataract surgery) and non-visual Physical Impairments (co-morbidities not
      affected by cataract surgery). RESULTS: In this prospective study, the average
      Visual Impairment score improved by 19 points (65%) following cataract extraction
      (the mean HVAT Visual Impairment score was 29 points before surgery and 10 points
      at 5 months post-surgery, a change of 65%). Physical Impairment remained
      unchanged by surgery. Visual acuity was a poor predictor of Visual Impairment.
      CONCLUSIONS: The HVAT has 11 simple questions. It may be self-administered and is
      available on the Internet: http://www.DHAC.com. The physician may err if his
      decision in favor of cataract surgery is based only on visual acuity. The HVAT
      has the potential to guide the decision-making process between patient and
      physician.

PMID- 10934461
TI  - Diabetes, fasting blood glucose and age-related cataract: the Blue Mountains Eye
      Study.
AB  - AIMS: To examine the relationship between diabetes and the presence of cortical,
      nuclear and posterior subcapsular (PSC) cataract in a defined older population,
      while controlling for known cataract risk factors. METHODS: Slit-lamp and
      retroillumination lens photographs were taken on 3654 participants attending the
      population-based Blue Mountains Eye Study during 1992-94. Masked grading of the
      photographs was performed using the Wisconsin Cataract Grading System. RESULTS:
      217 subjects (5.9% of the population) had previously diagnosed diabetes and 66
      (1.8%) had diabetes diagnosed from fasting blood glucose measurements. Cortical
      cataract, PSC and past cataract surgery were associated with known diabetes in
      age-sex adjusted models. However, only PSC (odds ratio (OR) 1.8, 95% confidence
      interval (CI) 1.0-3.1) and past cataract surgery (OR 2.5, CI 1.5-4.2) remained
      statistically significantly associated with diabetes after further adjustment for
      other known cataract risk factors. Increasing therapy, as an index of diabetes
      severity (oral or insulin treatment, compared to treatment by diet alone), was
      associated with a markedly increased risk of PSC (OR 5.4). CONCLUSIONS: These
      findings support previous research showing that diabetes has a harmful effect on
      the lens. The markedly increased risk for PSC may also have been reflected in the
      association found between diabetes and past cataract surgery. Contrary to
      findings from the Beaver Dam Eye Study, we found only a weak association with
      cortical cataract, which was not statistically significant after adjusting for
      other known cataract risk factors.

PMID- 10934463
TI  - Regional variation in blindness in children due to microphthalmos, anophthalmos
      and coloboma.
AB  - BACKGROUND: The prevalence and causes of blindness in children vary widely
      between regions. Few epidemiological data are available on the relative
      importance of the major congenital anomalies of the globe (i.e., microphthalmos,
      anophthalmos, coloboma) as causes of blindness in children. The aim of this study
      was to determine the re-gional variation in the proportion of severe visual
      impairment and blindness due to congenital abnormalities of the globe in children
      in schools for the blind and in those identified through Community Based
      Rehabilitation programs. Other objectives were to estimate the prevalence of
      blindness due to major congenital abnormalities, and to investigate their
      etiology. METHODS: Data on the causes of blindness in children were collected
      between 1990 and 1998 using standard methods, definitions and reporting form in
      26 countries. Children were examined in schools for the blind and in Community
      Based Rehabilitation programs. RESULTS: Of 7,113 children aged 3-15 years with
      severe visual impairment and blindness examined, 762 (10.7%) had microphthalmos,
      161 (2.3%) had anophthalmos, and 96 (1.3%) had coloboma. There are large regional
      differences in the proportion of severe visual loss in blind school children,
      ranging from 1.4% in Cuba to 33.2% in Sri Lanka. Severe visual loss due to
      congenital abnormalities of the globe is estimated to affect between 0.4 and
      16.2/100,000 children in the countries studied. An underlying cause could not be
      identified in 84.2%. CONCLUSIONS: Major congenital abnormalities of the globe are
      important causes of severe visual loss in children, particularly in Asian
      countries. Further research into etiology is warranted in order to plan
      prevention programs.

PMID- 10934462
TI  - Baseline self-reported cataract and subsequent mortality in Physicians' Health
      Study I.
AB  - PURPOSE: To examine whether a reported history of cataract, a possible marker of
      aging, is associated with future mortality. METHODS: Participants were 18,669 of
      the 22,071 U.S. male physicians enrolled in the Physicians' Health Study I who
      had complete information at study entry, including self-report of presence or
      absence of baseline cataract. Participants were without a previous history of
      myocardial infarction, stroke, transient cerebral ischemia, or cancer (except non
      melanoma skin cancer). Reported deaths were confirmed by an End Points Committee
      of physicians. RESULTS: A total of 581 participants reported a personal history
      of cataract at baseline. During an average of 12.4 years of follow-up, there were
      1,514 deaths including 496 due to cardiovascular (CV) and 1,018 due to non-CV
      causes. After adjustment for differences in age, men who reported cataract at
      baseline had a non-significant 9% increased risk of death from any cause compared
      to men who did not report cataract (RR, 1.09; 95% CI, 0.91-1.30). The RRs were
      1.03 (95% CI, 0.75-1.41) for CV death and 1.12 (95% CI, 0.90-1.40) for non-CV
      death. Adjustment for other risk factors had little effect on these estimates.
      Similar results were obtained in analyses conducted separately among those with
      and without self-reported diabetes at baseline. CONCLUSIONS: These results from a
      population of generally healthy physicians indicate that a report of a history of
      cataract is not associated with any material increase in mortality after
      adjustment for differences in age between men with and without cataract.
      Additional investigation of this cohort is in progress to determine whether
      incident age-related cataracts as well as their subtypes, confirmed by medical
      record review, are associated with increased mortality.

PMID- 10934464
TI  - Serious fireworks-related eye injuries.
AB  - OBJECTIVE: To analyze and compare epidemiological and clinical information on
      serious fireworks-related eye injuries from two affiliates of the United States
      Eye Injury Registry. METHOD: Retrospective review. RESULTS: In the Eye Injury
      Registry of Alabama (EIRA) database, 185 of the 4150 injuries (4.4%) were caused
      by fireworks. In the Hungarian Eye Injury Registry database, only two of the 1245
      cases (0.1%, p=0.000001) were fireworks-related. In the EIRA, 79% of patients
      were males and 87% were under 31 years. A bystander was injured in 67% of the
      cases, being an average of 23 feet away; 39% of bystanders had a final vision <
      or =19/200. No injured person wore eye protection. Bottle rockets caused 80% of
      the 185 injuries. Overall, 20% of eyes had <5/200 final visual acuity. Twenty
      five percent of bottle rocket-injured eyes, compared to 64% of those injured by
      other devices, had > or =20/40 final vision (p=0. 000004). CONCLUSIONS. The rate
      of fireworks-related serious eye injuries has not decreased in Alabama in the
      last 16 years; most patients are young males. Since bystanders are at a
      measurable risk even at a distance of 100 feet, wearing eye protection is
      recommended to both bystanders and operators. Bottle rockets cause most of the
      injuries and the more severe ones, and should be the prime target for prevention.
      The benefit of a strict and enforced legislative ban on private fireworks
      displays is demonstrated by the much lower incidence figure in Hungary. Such a
      ban should be considered in other countries where fireworks-related eye injuries
      are common.

PMID- 10934465
TI  - A survey of vernal keratoconjunctivitis and other eosinophil-mediated external
      eye diseases amongst Palestinians.
AB  - PURPOSE: To determine the morbidity of vernal, atopic and other disease mediated
      by eosinophils amongst the Palestinian Community of East Jerusalem, West Bank and
      Gaza Strip. METHOD: In a prospective outpatient study, 840 people were screened
      for evidence of eosinophilic external eye disease by history taking and medical
      examination of the external eye, conjunctiva, nose and paranasal sinuses in the
      outpatient clinic. The surgical and iatrogenic morbidity of the condition was
      concurrently estimated, and the prescribing habits of local West Bank
      ophthalmologists were carefully evaluated. The favoured regime was locally
      manufactured antihistamine drops, usually in combination with an aminoglycoside
      antibiotic that characteristically exacerbates the condition. Topical steroids,
      such as guttae prednisolone forte, were also overused as a modality to treat the
      condition. CONCLUSIONS: Since the recent decline of endemic trachoma, vernal eye
      disease is now the leading cause of outpatient ophthalmic morbidity amongst
      Palestinians of East Jerusalem. The disease accounts for at least 9. 8% of
      approximately 74,400 annual outpatient attendances to ophthalmic clinics in East
      Jerusalem, the West Bank and Gaza. The manifestations of the disease, however,
      are more protean than this. In the context of poor hygiene and sometimes dubious
      medical practice, vernal eye disease is often responsible for serious anterior
      segment and external ophthalmic disease.

PMID- 10934466
TI  - Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase
      9 to the Apaf-1 apoptosome.
AB  - The cellular-stress response can mediate cellular protection through expression
      of heat-shock protein (Hsp) 70, which can interfere with the process of apoptotic
      cell death. Stress-induced apoptosis proceeds through a defined biochemical
      process that involves cytochrome c, Apaf-1 and caspase proteases. Here we show,
      using a cell-free system, that Hsp70 prevents cytochrome c/dATP-mediated caspase
      activation, but allows the formation of Apaf-1 oligomers. Hsp70 binds to Apaf-1
      but not to procaspase-9, and prevents recruitment of caspases to the apoptosome
      complex. Hsp70 therefore suppresses apoptosis by directly associating with Apaf-1
      and blocking the assembly of a functional apoptosome.

PMID- 10934467
TI  - Negative regulation of the Apaf-1 apoptosome by Hsp70.
AB  - Release of cytochrome c from mitochondria by apoptotic signals induces ATP/dATP
      dependent formation of the oligomeric Apaf-1-caspase-9 apoptosome. Here we show
      that the documented anti-apoptotic effect of the principal heat-shock protein,
      Hsp70, is mediated through its direct association with the caspase-recruitment
      domain (CARD) of Apaf-1 and through inhibition of apoptosome formation. The
      interaction between Hsp70 and Apaf-1 prevents oligomerization of Apaf-1 and
      association of Apaf-1 with procaspase-9. On the basis of these results, we
      propose that resistance to apoptosis exhibited by stressed cells and some
      tumours, which constitutively express high levels of Hsp70, may be due in part to
      modulation of Apaf-1 function by Hsp70.

PMID- 10934468
TI  - CENP-E forms a link between attachment of spindle microtubules to kinetochores
      and the mitotic checkpoint.
AB  - Here we show that suppression of synthesis of the microtubule motor CENP-E
      (centromere-associated protein E), a component of the kinetochore corona fibres
      of mammalian centromeres, yields chromosomes that are chronically mono
      orientated, with spindles that are flattened along the plane of the substrate.
      Despite apparently normal microtubule numbers and the continued presence at
      kinetochores of other microtubule motors, spindle poles fragment in the absence
      of CENP-E, which implicates this protein in delivery of components from
      kinetochores to poles. CENP-E represents a link between attachment of spindle
      microtubules and the mitotic checkpoint signalling cascade, as depletion of this
      motor leads to profound checkpoint activation, whereas immunoprecipitation
      reveals a nearly stoichiometric association of CENP-E with the checkpoint kinase
      BubR1 during mitosis.

PMID- 10934469
TI  - Cohesin ensures bipolar attachment of microtubules to sister centromeres and
      resists their precocious separation.
AB  - The multisubunit protein complex cohesin is required to establish cohesion
      between sister chromatids during S phase and to maintain it during G2 and M
      phases. Cohesin is essential for mitosis, and even partial defects cause very
      high rates of chromosome loss. In budding yeast, cohesin associates with specific
      sites which are distributed along the entire length of a chromosome but are more
      dense in the vicinity of the centromere. Real-time imaging of individual
      centromeres tagged with green fluorescent protein suggests that cohesin bound to
      centromeres is important for bipolar attachment to microtubules. This cohesin is,
      however, incapable of resisting the consequent force, which leads to sister
      centromere splitting and chromosome stretching. Meanwhile, cohesin bound to
      sequences flanking the centromeres prevents sister chromatids from completely
      unzipping and is required to pull back together sister centromeres that have
      already split. Cohesin therefore has a central role in generating a dynamic
      tension between microtubules and sister chromatid cohesion at centromeres, which
      lasts until chromosome segregation is finally promoted by separin-dependent
      cleavage of the cohesin subunit Scc1p.

PMID- 10934470
TI  - Formation of the male-specific muscle in female Drosophila by ectopic fruitless
      expression.
AB  - The Drosophila fruitless (fru) gene product Fru has been postulated to be a
      neural sex-determination factor that directs the development of at least two male
      specific characteristics, namely courtship behaviour and formation of the muscle
      of Lawrence (MOL). The fru gene encodes a putative transcription factor with a
      BTB domain and two zinc-finger motifs, and with consensus Tra-binding sequences.
      The binding of Tra to these sequences results in sex-specific alternative
      splicing of the fru mRNA, leading to production of the 'male-type' or 'female
      type' Fru protein. We show here that the Fru protein is not detected in the
      female central nervous system (CNS), despite the similar level of expression of
      fru mRNA in both male and female CNS. As ectopic expression of both the 'male
      type' (with the sequence for the amino-terminal extension) and 'female-type'
      (without the sequence for the amino-terminal extension) fru cDNA can induce
      formation of the MOL in females, the presence or absence of the Fru protein, and
      not its sex-specific structure, seems to be responsible for the sexually
      dimorphic actions of the fru gene.

PMID- 10934471
TI  - Receptor-mediated hydrolysis of plasma membrane messenger PIP2 leads to K+
      current desensitization.
AB  - Phosphatidylinositol bisphosphate (PIP2) directly regulates functions as diverse
      as the organization of the cytoskeleton, vesicular transport and ion channel
      activity. It is not known, however, whether dynamic changes in PIP2 levels have a
      regulatory role of physiological importance in such functions. Here, we show in
      both native cardiac cells and heterologous expression systems that receptor
      regulated PIP2 hydrolysis results in desensitization of a GTP-binding protein
      stimulated potassium current. Two receptor-regulated pathways in the plasma
      membrane cross-talk at the level of these channels to modulate potassium
      currents. One pathway signals through the betagamma subunits of G proteins, which
      bind directly to the channel. Gbetagamma subunits stabilize interactions with
      PIP2 and lead to persistent channel activation. The second pathway activates
      phospholipase C (PLC) which hydrolyses PIP2 and limits Gbetagamma-stimulated
      activity. Our results provide evidence that PIP2 itself is a receptor-regulated
      second messenger, downregulation of which accounts for a new form of
      desensitization.

PMID- 10934472
TI  - Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and
      Notch2.
AB  - Proteins encoded by the fringe family of genes are required to modulate Notch
      signalling in a wide range of developmental contexts. Using a cell co-culture
      assay, we find that mammalian Lunatic fringe (Lfng) inhibits Jagged1-mediated
      signalling and potentiates Delta1-mediated signalling through Notch1. Lfng
      localizes to the Golgi, and Lfng-dependent modulation of Notch signalling
      requires both expression of Lfng in the Notch-responsive cell and the Notch
      extracellular domain. Lfng does not prevent binding of soluble Jagged1 or Delta1
      to Notch1-expressing cells. Lfng potentiates both Jagged1- and Delta1-mediated
      signalling via Notch2, in contrast to its actions with Notch1. Our data suggest
      that Fringe-dependent differential modulation of the interaction of
      Delta/Serrate/Lag2 (DSL) ligands with their Notch receptors is likely to have a
      significant role in the combinatorial repertoire of Notch signalling in mammals.

PMID- 10934473
TI  - p95-APP1 links membrane transport to Rac-mediated reorganization of actin.
AB  - Motility requires protrusive activity at the cellular edge, where Rho family
      members regulate actin dynamics. Here we show that p95-APP1 (ArfGAP-putative, Pix
      interacting, paxillin-interacting protein 1), a member of the GIT1/PKL family, is
      part of a complex that interacts with Rac. Wild-type and truncated p95-APP1
      induce actin-rich protrusions mediated by Rac and ADP-ribosylation factor 6
      (Arf6). Distinct p95-APP1-derived polypeptides have different distributions,
      indicating that p95-APP1 cycles between the cell surface and endosomes. Our
      results show that p95-APP1 functionally interacts with Rac and localizes to
      endosomal compartments, thus identifying p95-APP1 as a molecular link between
      actin organization, adhesion, and membrane transport during cell motility.

PMID- 10934474
TI  - The cell-polarity protein Par6 links Par3 and atypical protein kinase C to Cdc42.
AB  - PAR (partitioning-defective) proteins, which were first identified in the
      nematode Caenorhabditis elegans, are essential for asymmetric cell division and
      polarized growth, whereas Cdc42 mediates establishment of cell polarity. Here we
      describe an unexpected link between these two systems. We have identified a
      family of mammalian Par6 proteins that are similar to the C. elegans PDZ-domain
      protein PAR-6. Par6 forms a complex with Cdc42-GTP, with a human homologue of the
      multi-PDZ protein PAR-3 and with the regulatory domains of atypical protein
      kinase C (PKC) proteins. This assembly is implicated in the formation of normal
      tight junctions at epithelial cell-cell contacts. Thus, Par6 is a key adaptor
      that links Cdc42 and atypical PKCs to Par3.

PMID- 10934475
TI  - A mammalian PAR-3-PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and
      cell polarity.
AB  - Cellular asymmetry is critical for the development of multicellular organisms.
      Here we show that homologues of proteins necessary for asymmetric cell division
      in Caenorhabditis elegans associate with each other in mammalian cells and
      tissues. mPAR-3 and mPAR-6 exhibit similar expression patterns and subcellular
      distributions in the CNS and associate through their PDZ (PSD-95/Dlg/ZO-1)
      domains. mPAR-6 binds to Cdc42/Rac1 GTPases, and mPAR-3 and mPAR-6 bind
      independently to atypical protein kinase C (aPKC) isoforms. In vitro, mPAR-3 acts
      as a substrate and an inhibitor of aPKC. We conclude that mPAR-3 and mPAR-6 have
      a scaffolding function, coordinating the activities of several signalling
      proteins that are implicated in mammalian cell polarity.

PMID- 10934476
TI  - Stimulation of erythropoiesis by inhibiting a new hematopoietic death receptor in
      transgenic zebrafish.

PMID- 10934477
TI  - BAX-dependent transport of cytochrome c reconstituted in pure liposomes.

PMID- 10934478
TI  - Anaphase spindle position is monitored by the BUB2 checkpoint.

PMID- 10934479
TI  - The nuclear import function of Smad2 is masked by SARA and unmasked by TGFbeta
      dependent phosphorylation.

PMID- 10934480
TI  - In search of a function.

PMID- 10934481
TI  - Ubiquitin biology: an old dog learns an old trick.
AB  - Regulated protein degradation in eukaryotes occurs principally through covalent
      tagging of substrates with ubiquitin, thereby targeting them for destruction by
      26S proteasomes. Classical allostery has now been added to the repertoire of
      mechanisms that can modulate ubiquitin tagging, allowing feed-forward regulation
      to be achieved through targeted protein destruction.

PMID- 10934482
TI  - Growth and polarity: the case for scribble.

PMID- 10934483
TI  - LAP proteins: what's up with epithelia?
AB  - How cells maintain their overall shape and size, and the related question of how
      proteins and other molecules reach and stay at their specific subcellular
      locations, are among the most difficult and exciting problems in cell biology.
      Three recent studies have made a significant contribution to this area by
      identifying new proteins, called LAP proteins, that have critical functions in
      maintaining the shape and apical-basal polarity of epithelial cells.

PMID- 10934484
TI  - Cell polarity: new PARtners for Cdc42 and Rac.
AB  - Three recent papers have reported the surprising finding that Cdc42 and Rac1,
      both of which are known to be involved in maintaining apico-basolateral polarity
      of epithelial cells, can each bind to a protein complex containing Par6, Par3 and
      PKCzeta. These latter three proteins have known functions in the polarization of
      mother cells before asymmetric cell division in Caenorhabditis elegans. These
      latest results indicate a possible link between the mechanisms used to maintain
      cell polarity and to set up asymmetric cell divisions.

PMID- 10934485
TI  - The consequences of incontinentia pigmenti.

PMID- 10934488
TI  - Deciphering the structure of living beings

PMID- 10934487
TI  - Honest Jim

PMID- 10934486
TI  - Multi-layered regulation of courtship behaviour.
AB  - The fruitless gene governs courtship in male, but not female, Drosophila, yet it
      is expressed and specifically spliced in the brains of both sexes. New
      experiments reveal that a splice-recognition site retained in the mature message
      in females provides the basis for sex-specific translational repression.

PMID- 10934489
TI  - Negative thinking: anion channels claim their rights

PMID- 10934490
TI  - Lessons from the history of light microscopy.
AB  - Historically, the late arrival of optical microscopy is something of a puzzle,
      although it may be a testament to the fact that the development of new technology
      is driven by the desire for scientific knowledge, and not the other way around.
      The explorations that began in the 17th century are by no means complete, but who
      is carrying them forward now?

PMID- 10934491
TI  - Evolution and function of ubiquitin-like protein-conjugation systems.
AB  - Ubiquitin functions by covalently modifying other proteins. In the past few
      years, a surprising number of other proteins have been identified that, despite
      often being only slightly similar to ubiquitin, can also be attached to proteins.
      Newly discovered parallels between the activation of ubiquitin and the
      biosynthesis of certain enzyme cofactors now hint at the possible evolutionary
      origins of the ubiquitin system.

PMID- 10934492
TI  - Prevention of systemic mycoses in patients who are not neutropenic: should we do
      it? Can we do it?
AB  - It has been well documented that serious fungal infections may cause death in 5%
      to 10% of patients in certain high risk groups, such as those undergoing lung,
      pancreas, or liver transplantation. Patients in intensive care units, such as
      those with underlying severe disease, multi-organ fungal infection, those with
      catheters, those on broad spectrum antibacterial agents, and those in renal
      failure are also at risk and may be candidates for antifungal prophylaxis.
      However, recommendations regarding the use of antifungal drugs for prophylaxis in
      non-neutropenic patients are unclear. Several clinical trials in transplant
      recipients have supported the use of fluconazole for prophylaxis, particularly in
      liver transplantation, though the data are too few to permit generalized
      conclusions for all organ transplant recipients. There is also a trial in which
      antifungal prophylaxis has been successful after gut perforation. However, there
      are also reports in which high doses of fluconazole have not reduced fungal
      infection. The appropriate circumstances for prophylaxis are still undergoing
      definition. It is the author's opinion that effective prophylaxis will become
      more problematic in the future. In a year or two, once the drug becomes generic,
      the price of fluconazole will fall dramatically. A sharp increase in use is
      likely to occur, and is likely to be followed by increasing fluconazole
      resistance in both Candida albicans and non-albicans colonization and infections.
      The situation is similar to the consequences of widespread fluconazole use in
      AIDS patients. The best methods to delay resistance include strict handwashing,
      careful control of antibacterials, restricting fluconazole use to those
      situations where it has been most clearly shown to be beneficial, and carefully
      monitoring patients in intensive care units.

PMID- 10934493
TI  - Epidemiology and treatment of hematogenous candidiasis: a Brazilian perspective.
AB  - Hematogenous candidemia is an increasingly frequent problem among patients who
      are immunosuppressed, receiving parenteral nutrition and/or antibiotics, or who
      have invasive medical devices such as indwelling catheters. In Brazil, Candida
      albicans was responsible for 53/145 (37%) of candidemia in 6 different tertiary
      care hospitals. The most common non-albicans species were C. parasilosis (25%),
      C. tropicalis (24%), C. rugosa (5%) and C. glabrata (4%). The main risk factors
      for infection were antibiotic use and the presence of a central venous catheter.
      The main risk factors for mortality were patient age (older patients at risk) and
      not removing the catheter. Because of the great number of non-albicans species
      and varied degrees of antifungal drug sensitivity, laboratory identification and
      sensitivity testing is very important. All patients with documented candidemia
      should be treated. Drugs to be used are amphotericin B and/or fluconazole.
      Fluconazole resistance is not yet a problem in Brazil, perhaps because it is
      rarely used as prophylaxis due to its high cost. Intravenous catheters should be
      removed immediately if the patient has a short term catheter, or if the patient
      is clinically unstable due to the infection and has a long term catheter in
      place.

PMID- 10934494
TI  - Molecular epidemiology of group A rotavirus causing acute diarrhea in infants and
      young children hospitalized in Rio de Janeiro, Brazil, 1995-1996.
AB  - During 1995-1996, an epidemiological survey was conducted at Fernandes Figueira
      Institute (Rio de Janeiro, DC) on group A rotavirus strains causing acute
      diarrhea in infants and young children. Rotaviruses were detected in 15.7% of
      examined specimens. Among the rotavirus strains tested for dsRNA by PAGE, 70%
      belonged to the long pattern and 30% to the short pattern. A long pattern
      classified as LA was the prevalent electropherotype among all of the types, and
      the prevalent short pattern was a unique SA type. Fifteen years ago, LA type was
      prevalent in the city among long patterns, and a SB type among short patterns,
      showing a substitution of circulating electropherotypes. The long pattern
      occurred throughout the period studied and in all age ranges studied (0-5 years
      old), but the short pattern occurred only in young children (age range 0-11
      months) in May 1995, and September 1996. The data demonstrate epidemiologic
      differences between long and short electropherotypes incidence; the long
      electropherotype strains circulate throughout the community and the short
      electropherotype strains appear only in young children. Rotavirus was observed
      throughout the period studied but there were peaks of infection in the months of
      May and September.

PMID- 10934495
TI  - HTLV-I associated myelopathy: clinical and epidemiological profile.
AB  - The prevalence of HTLV-I reaches 1.8% among blood donors in Salvador, and 40%
      among chronic myelopathy patients in the state of Bahia, Brazil. The present
      study shows the epidemiological and clinical picture of patients attending the
      HAM/TSP Outpatient Unit at the Foundation of Neurology and Neorusurgery (FNN).
      114 patients had epidemiologic data collected and 51 of these patients, who had
      regularly attended the HAM/TSP Unit for at least 1 year, were evaluated for
      signs, symptoms and disease progression. Most of the 114 patients were female
      (70%), of African descent, and with a mean age of 51. Sexually transmitted
      diseases and blood transfusion were the most common risk factors. Paraparesis
      with spasticity was the predominant sign (85%), bladder dysfunction occurred in
      75%, intestinal dysfunction was recorded in 48%. Sensory examination was normal
      in 50% of the cases studied. The patients' functional status, as measured by the
      Kurtzke Disability Scale, during the 1 year observation period changed only in
      early disease. Steroid therapy with prednisone was the most commonly used
      treatment in this group.

PMID- 10934496
TI  - The relationship between rainfall and human leptospirosis in Florianopolis,
      Brazil, 1991-1996.
AB  - The relationship between serologically confirmed cases of leptospirosis and the
      amount of rainfall in greater Florianopolis, in southern Brazil, was studied
      retrospectively for the period 1991 to 1996. Maximum daily and total monthly
      rainfall for present and previous months were statistically significant
      predictors of the number of cases of leptospirosis in Poisson regression models.
      However, daily maximum rainfall data showed a much better model fit than total
      monthly rainfall. For each millimeter increase in maximum daily rainfall for the
      month above the average for the period studied, there was an increase of 0.55% in
      the number of leptospirosis cases relative to the period average. For the past
      month's daily maximum, this increase was 0.21%. Maximum daily rainfall during the
      month is a sensitive indicator of large amounts of rain falling in a brief period
      of time. This may cause flash floods and, thus, disseminate pathogenic Leptospira
      among the human population, particularly in densely populated areas with large
      rodent populations and without adequate drainage. This situation is typical for
      the association of tropical rainstorms and the spread of leptospirosis among slum
      dwellers.

PMID- 10934497
TI  - Risk factors for methicillin resistant and sensitive Staphylococcus aureus
      infection in a Brazilian university hospital.
AB  - Two hundred three isolates of S. aureus were collected from 140 patients during a
      1 year period in our hospital in Minas Gerais, Brazil. Of these patients, 102
      acquired the infection in the hospital (nosocomial) and are the subject of this
      report. Fifty-seven patients had Methicillin-sensitive S. aureus (MSSA) strains
      identified, and 45 had Methicillin-resistant S. aureus (MRSA) strains. The most
      common sites of clinical infections by S. aureus were bloodstream (bacteremia),
      surgical/skin wounds and lung (pneumonia). The patients with MRSA infections were
      most likely to be in the surgical and clinical wards, but those with MSSA
      infections were most likely to be in the neonatal and emergency units. By
      univariate analysis, we found several factors associated with an increased risk
      of MRSA infections: age, mean preinfections and total duration of hospital stay,
      use of 3 or more antimicrobials, presence of 3 or more indwelling devices (mainly
      vascular and urinary catheters). Colonization (67.6% x 27.8%; p<0.05) and
      multicolonization (89% x 11.0%; p<0.05) were more associated with MRSA infection.
      Of the total of 203 isolates, 110 MRSA were found to be multiresistant, with 106
      showing resistance to 5 or more antibiotics, compared to 15/93 (16%) of the MSSA
      isolates. The most serious cases and higher colonization rates of MRSA occurred
      in elderly patients. The presence of nosocomial MRSA is a serious medical problem
      which requires continued attention to care in the overuse of antibiotics and
      indwelling devices in hospitals.

PMID- 10934498
TI  - Detecting polysaccharide antigen of Neisseria meningitidis group C in
      cerebrospinal fluid by dot-ELISA assay.
AB  - Cerebrospinal fluid (CSF) samples from 210 patients (200 with clinical evidence
      of bacterial meningitis, 10 with other clinical neurologic disease) were tested
      by a Dot-ELISA assay for detection of polysaccharide antigen of N. meningitidis
      group C. CSF samples were treated with EDTA 0.1 M, at pH 7.5 and heated to 90>C
      for 10 min. Polyclonal antiserum was purified by use of ethanol fractionation.
      The results were compared to those using bacterial culture (BC), latex
      agglutination (LA), counterimmunoelectrophoresis (CIE), and direct microscopy
      (DM) methods. Test results showed a correlation of 93.3%, 94.3%, 91.0% and 69.5%
      respectively, and sensitivity of 0.947 and specificity of 0.930. This study
      suggests that the dot-ELISA assay of CSF is a useful alternative technique for
      the diagnosis of group C meningitis.

PMID- 10934499
TI  - Lactic acidosis and antiretroviral therapy: a case report and literature review.
AB  - Antiretrovirals, particularly nucleoside analogue reverse transcriptase
      inhibitors (RTIs) - DDI, 3TC and D4T, are widely used to effectively control
      human immunodeficiency virus (HIV) infection. These drugs have several adverse
      effects including anemia, peripheral neuropathy, pancreatitis and, on rare
      occasions, lactic acidosis. We describe the case of a 39 year old patient who had
      severe lactic acidosis after receiving stavudine (D4T) and didanosine (DDI) for
      an 8 month period. She had never manifested an opportunistic infection and
      presented a CD4 count of 378 cells/mm3 and an undetectable viral load (< 400
      copies/ml). The purpose of the following report is to alert clinicians and
      infectious diseases specialists to the occurrence of lactic acidosis in
      asymptomatic HIV patients receiving antiretrovirals for long periods of time.

PMID- 10934500
TI  - Vaccines for the future: problems and potential solutions from the countries that
      need them.

PMID- 10934501
TI  - Fighting spirit.

PMID- 10934502
TI  - Suggestions, commendations, and recommendations.

PMID- 10934503
TI  - Qigong database.

PMID- 10934504
TI  - Medicine and story: a novel clinical panorama arising from a unitary mind/body
      approach to physical illness.
AB  - Since 1987, all patients referred by family physicians for internal medicine
      consultation at the Institute for Integrative Health Studies (Christchurch, New
      Zealand) have been assessed by the author from both physical (normative internal
      medicine) and psychological (psychodynamic, interpersonal, object relations, and
      self psychological) perspectives. Depending upon the material emerging in each
      case, the treatment options available for the particular disorder, and patient
      preferences, many patients have gone on to mind/body oriented discussions or
      psychotherapy with the author (detailed in Broom 1997), or with one of a team of
      therapists supervised by the author. This clinical experience, mixing internal
      medicine and psychotherapy approaches to physical illnesses (with or without
      organic findings), points to the following: (1) Profound connections between the
      patients' perceptions of their life-events and experience and the development of
      illness in both organic and nonorganic illnesses; (2) a rich fund of information
      in the patients' verbal language about the meaning of the illnesses; (3) the
      crucial importance of clinical attunement to macro- and micro-life events
      surrounding symptom emergence; and (4) the decisive role a clinician's implicit
      paradigm of "personhood" plays in patient care. This paper broadly outlines the
      presuppositions for this integrative clinical approach, and illustrates the
      approach with case material. Additionally, it summarizes the kinds of listening,
      and other skills, that have proved clinically useful. In all, the material
      illustrates that a combination of orthodox biomedical approaches and a "story
      approach" (which focuses on meaning leading to illness) offers considerable
      potential benefits to patients with physical symptomatologies including those
      with organic findings.

PMID- 10934505
TI  - Broom's story.

PMID- 10934506
TI  - The difference between taking an anamnesis and listening to a (life) story.

PMID- 10934507
TI  - The role of narrative in medicine: a multi-theoretical perspective.

PMID- 10934508
TI  - Story, medicine, and healthcare.

PMID- 10934510
TI  - Broom responds

PMID- 10934509
TI  - Patient narratives.

PMID- 10934511
TI  - Abstracts of recently published studies

PMID- 10934512
TI  - Placebo and health--II. How to produce not only powerful but, more importantly,
      reliable placebo healing and analgesia.

PMID- 10934513
TI  - Placebo and health-II

PMID- 10934515
TI  - A bridge for consciousness--II. Knowledge management and consciousness.

PMID- 10934516
TI  - Events and websites

PMID- 10934514
TI  - Placebo and health--II. Three perspectives on the placebo response: expectancy,
      conditioning, and meaning.

PMID- 10934517
TI  - The FokI methyltransferase from Flavobacterium okeanokoites. Purification and
      characterization of the enzyme and its truncated derivatives.
AB  - The gene encoding the FokI methyltransferase from Flavobacterium okeanokoites was
      cloned into an Escherichia coli vector. The transcriptional start sites were
      mapped as well as putative -10 and -35 regions of the fokIM promoter. Enzyme
      overproduction was ensured by cloning the fokIM gene under the phi 10 promoter of
      phase T7. M.FokI was purified using a two-step chromatography procedure. M.FokI
      is a monomeric protein with a M(r) = 76,000 +/- 1,500 under denaturing
      conditions. It contains 21 Arg residues, and at least one of which is required
      for activity as shown by inhibition using 2,3-butanedione. Deletion mutants in
      the N- and C-terminus of M.FokI were isolated and characterized. The N-terminal
      derivative (M.FokIN) methylates the adenine residue within the sequence 5'-GGATG
      3', whereas the C-terminal derivative (M.FokIC) modifies the adenine residue
      within the sequence 5'-CATCC-3'. Substrate-protection studies, utilizing chemical
      modification combined with data on the effect of divalent cations and pH on
      methylation activity, proved the existence of two catalytic centers within the
      FokI methyltransferase molecule. M.FokI and its truncated derivatives require S
      adenosyl-L-methionine as the methyl-group donor, and they are strongly inhibited
      by divalent cations (Mg2+, Ca2+, Ba2+, Mn2+, and Zn2+) and S-adenosyl-L
      homocysteine. The Km values for the methyl donor, S-adenosyl-L-methionine are 0.6
      microM (M.FokI), 0.4 microM (M.FokIN), and 0.9 microM (M.FokIC) while the Km
      values for substrate lambda DNA are 1.2 nM (M.FokI), 1.4 nM (M.FokIN), and 1.3 nM
      (M.FokIC).

PMID- 10934518
TI  - A simple and rapid method for isolating myelin basic protein.
AB  - The conduction of impulses along axons of nerves is facilitated by the myelin
      sheath, composed of proteins and lipid. Myelin basic proteins (MBPs) are
      extrinsic membrane proteins that play an important role in the structural
      organization of the myelin sheath. In the central nervous system, MBPs account
      for 30-40% of total protein. The traditional method of MBP isolation involves the
      use of chloroform-ethanol, which would destroy the native form of MBP. A modified
      method for maintaining its native form was developed. The white matter of porcine
      brain was directly extracted by buffers containing different concentrations of
      sodium chloride owing to MBP solubilized at high concentration of NaCl. The MBP
      was further purified by cation exchange chromatography and buffers containing
      glycine and salts. Purified MBP were consistently obtained by this method.

PMID- 10934519
TI  - Therapeutic genes for cancer gene therapy.
AB  - Cancer still represents a disease of high incidence and is therefore one major
      target for gene therapy approaches. Gene therapy for cancer implies that ideally
      selective tumor cell killing or inhibition of tumor cell growth can be achieved
      using nucleic acids (DNA and RNA) as the therapeutic agent. Therefore, the
      majority of cancer gene therapy strategies introduce foreign genes into tumor
      cells which aim at the immunological recognition and destruction, the direct
      killing of the target cells or the interference with tumor growth. To achieve
      this goal for gene therapy of cancer, a broad variety of therapeutic genes are
      currently under investigation in preclinical and in clinical studies. These genes
      are of very different origin and of different mechanisms of action, such as human
      cytokine genes, genes coding for immunostimulatory molecules/antigens, genes
      encoding bacterial or viral prodrug-activating enzymes (suicide genes), tumor
      suppressor genes, or multidrug resistance genes.

PMID- 10934522
TI  - Methods for long-term virus preservation.
AB  - Viruses exhibit a wide variety of structural and chemical differences, but, in
      general, their infectivity may be destroyed by degradative enzymes that destroy
      nucleic acids, by detergents that solubilize the lipid-containing envelopes thus
      exposing the nucleic acid, by temperatures higher than about 50 degrees C, or by
      chemicals that breakdown capsid proteins. Preserving the viruses at low or ultra
      low temperatures, and/or in the absence of water, slows down these destructive
      processes sufficiently to increase significantly the length of time that the
      virus can be stored as infectious material. Supplements such as serum are
      presumed to stabilize the environmental conditions and to block degradative
      processes. The methods by which viruses may be preserved for long periods of time
      are similar to those employed for other microorganisms and are relatively simple.
      Nevertheless, attention to detail, good laboratory practice, aseptic technique,
      meticulous recordkeeping, and regular monitoring of the stored materials will
      increase the success rate and reduce problems of contamination or loss in the
      storage containers, where many different viruses may be stored for posterity!
      This article describes some of the simplest and most reliable storage procedures
      for viruses, but the author recognizes that everyone will have a favorite method
      to suit his or her own particular virus.

PMID- 10934521
TI  - Methods for studying prion protein (PrP) metabolism and the formation of protease
      resistant PrP in cell culture and cell-free systems. An update.
AB  - Transmissible spongiform encephalopathies (TSE) or prion diseases result in
      aberrant metabolism of prion protein (PrP) and the accumulation of a protease
      resistant, insoluble, and possibly infectious form of PrP, PrP-res. Studies of
      PrP biosynthesis, intracellular trafficking, and degradation has been studied in
      a variety of tissue culture cells. Pulse-chase metabolic labeling studies in
      scrapie-infected cells indicated that PrP-res is made posttranslationally from an
      apparently normal protease-sensitive precursor, PrP-sen, after the latter reaches
      the cell surface. Cell-free reactions have provided evidence that PrP-res itself
      can induce the conversion of PrP-sen to PrP-res in a highly species- and strain
      specific manner. These studies have shed light on the mechanism of PrP-res
      formation and suggest molecular bases for TSE species barrier effects and agent
      strain propagation.

PMID- 10934520
TI  - Reporter gene vectors and assays.
AB  - Gene reporter systems play a key role in gene expression and regulation studies.
      This review describes the ideal reporter systems, including reporter expression
      vector design. It summarizes the many uses of genetic reporters and outlines the
      currently available and commonly used reporter systems. Each system is described
      in terms of the reporter gene, the protein it encodes, and the assays available
      for detecting presence of the reporter. In addition, each reporter system is
      analyzed in terms of its recommended uses, advantages, and limitations.

PMID- 10934523
TI  - Transformation of nuclear and plastomic plant genomes by biolistic particle
      bombardment.
AB  - Microprojectile bombardment is a powerful method for the transformation of
      various organisms and tissues. For plants, the biolistic approach is primarily
      used for transformation of cereals and other monocotyledons, as well as for
      dicotyledonous plants shown to be recalcitrant to Agrobacterium-based
      transformation of organellar genomes, and transformation of plant and algal
      chloroplasts has recently been reported. In this protocol paper we provide
      methods for nuclear and plastomic transformation of plants using the biolistic
      technique.

PMID- 10934524
TI  - Generation of stable recombinant retroviruses containing the beta-globin genes
      linked to complex regulatory elements by using transient transfection.
AB  - A transient packaging method for a retroviral vector containing beta-globin
      sequences, mediated by Ca3(PO4)2 precipitation, generated stable recombinant beta
      globin retroviruses with intact viral genomes. We suggest the use of this method
      as an alternative means to overcome the production of beta-globin encoding
      retroviruses with aberrant viral genomes using the routine packaging procedure.

PMID- 10934525
TI  - Basic problems of serological laboratory diagnosis.
AB  - Serological laboratory diagnosis is inflicted with at least two kinds of basic
      problems. One type relates to the fact that the serological diagnosis of
      infectious diseases is double indirect: First, to diagnose an infectious disease,
      the identification of the microbial agent is sought that caused the disease.
      Second, to identify this infectious agent, the patient's immune response to
      potential agents is measured. So, the serological test is neither measuring
      directly disease nor the cause of the disease, but the patient's immune system.
      Another type of problem is based on the fact that each person's immune system is
      very individual. The exact physicochemical properties of antibodies are unique
      for each clone of antibodies. The way an individual's immune system sees an
      infectious agent depends not only on the genetic makeup of the person but also on
      the personal experience from former encounters with infectious agents. Both types
      of problems lead to complexities in selecting the appropriate test, in
      interpreting the results, and in standardizing serological tests. Therefore, a
      close collaboration of the laboratory with the clinic is mandatory to avoid
      erroneous conclusions from serological test results, which might lead to wrong
      decisions in patient care.

PMID- 10934526
TI  - Gene mapping by linkage and association analysis.
AB  - Genetic analysis is used to map genes, including disease loci, to positions
      within the human genome. Linkage analysis depends on the co-segregation of a gene
      (locus) and a phenotype through a pedigree, while association analysis, or
      linkage disequilibrium mapping, depends on measuring deviation from the random
      occurrence of alleles in a haplotype in unrelated individuals or nuclear
      families. Complex computer programs may be used in both forms of analysis. In
      recent years most interest has focused on identifying genes involved in common,
      multifactorial diseases. Here I review some current and developing techniques of
      genetic analysis and give references to where further information can be
      obtained.

PMID- 10934528
TI  - ABI sequencing analysis. Manipulation of sequence data from the ABI DNA
      sequencer.
AB  - The ABI Sequencing Analysis application is designed specifically for the analysis
      of data produced by the ABI DNA Sequencer. The ABI sequencer is a laser-based
      instrument that utilizes fluorescent labels to analyze the products of a
      sequencing reaction as they migrate through a gel. After the data are collected
      from a sequencing run, the Analysis program identifies and tracks the sample
      lanes of the gel and subsequently normalizes and integrates the raw data into a
      chromatogram of the final sequence. For the user, there are basically two types
      of files that can be manipulated to potentially improve the analysis results. The
      Gel File consists of a computer generated image of the sequencing gel with the
      fluorescent DNA banding patterns. This image allows the user to view and edit the
      tracking lines generated and used by Analysis to collect data points for each
      sample. Individual Sample Files are stored for each of the samples analyzed and
      include the chromatogram, raw data, and annotations and information regarding the
      sample and sequence run. Generally, the products of a sequencing reaction are
      easily resolved and the Analysis software interprets the correct nucleotide
      sequence. Ambiguous base calls tend to occur near the end of the sequence and may
      be either edited or deleted by the user before exporting the data for further
      comparisons or alignments. Occasionally the tracking lines within the gel image
      may need to be adjusted or moved. The sample data are then reextracted from the
      Gel File and analyzed again. This review explains the general operation of
      Analysis in terms of viewing and editing a chromatogram, retracking the lanes of
      a Gel File, and analyzing the final sample data. The three versions 1.2.1, 2.1.2,
      and 3.3 are discussed.

PMID- 10934527
TI  - Human identity testing with PCR-based systems.
AB  - Large numbers of repetitive stretches of DNA are present within the human genome
      that are associated with human individuality due to their polymorphic character.
      Approximately one-third of these repeat sequences is arranged as microsatellites
      or short tandem repeats (STRs) whose valuable application as state-of-the-art
      technique in human identity testing will be briefly summarized in this review.
      Prerequisites for successful DNA typing using STRs amplified by polymerase chain
      reaction (PCR) are outlined and particular attention is paid to the molecular
      structure of STRs from autosomes as well as from the Y chromosome. A
      comprehensive overview about current and emerging methods of STR analysis is
      given as well.

PMID- 10934529
TI  - Generation of baculovirus expression vectors.
AB  - The baculovirus expression system has become an important tool for the expression
      of heterologous genes because it has several positives attributes. First, high
      quantities of protein are produced because the target genes are driven by strong
      viral promoters. Second, most eukaryotic posttranslational modifications are
      carried out in insect cells in an authentic manner. Thus, proteins expressed with
      the baculovirus expression system usually have the same activities as the
      authentic protein. Several approaches have been developed to obtain recombinant
      baculoviruses easily and nowadays many modified baculoviral DNAs and a huge
      variety of transfer plasmids are available. Here, we described the rapid
      generation of recombinant baculoviruses using parental viral DNA that
      incorporates a lethal deletion and can be selected against. This basic approach
      should be suitable for the majority of applications.

PMID- 10934530
TI  - T-DNA transfer to maize plants.
AB  - Agrobacterium-mediated transformation is the method of choice to engineer
      desirable genes into plants. Here we describe a protocol for demonstrating T-DNA
      transfer from Agrobacterium into the economically important graminaceous plant
      maize. Expression of the T-DNA-located GUS gene was observed with high efficiency
      on shoots of young maize seedlings after cocultivation with Agrobacterium.

PMID- 10934531
TI  - Modification of the GeneScan 2500 fluorescent dye standard for accurate product
      sizing.
AB  - This article describes a procedure for modification of the commercially prepared
      GeneScan 2500 size standard for allelotyping with large DNA fragments such as
      variable number tandem repeats (VNTRs). Here a procedure was used to adapt
      commercially available size standards for the sizing of the interleukin-6 (IL6)
      3'VNTR, which has allele sizes ranging from 600 to 900 base pairs. The procedure
      involves inclusion of products from the target PCR reaction as additional size
      standards for use with the size standard and is therefore applicable to the
      sizing of any product with any commercial size standard. Initially alleles were
      sized by fluorescent cycle sequencing to give a true estimate of their size (base
      pairs). Subsequently, the major alleles were labeled with a pig-tailed ROX-dye
      labeled primer and inserted into the standard range. Finally alleles were resized
      following PCR with an un-pig-tailed HEX labeled primer and the modified standard.
      Once the size standard is modified, stocks can be stored indefinitely and
      replenished by re-PCR of selected alleles using the ROX-labeled primer.
      Modification of this approach can be applied to the sizing of any product where
      it is thought that commercially available size standards are performing
      suboptimally. Modification of size standards in this way does not affect
      performance in size regions other than those for which the extra products are
      included.

PMID- 10934532
TI  - Mycobacteria: bugs and bugbears (two steps forward and one step back).
AB  - The use of molecular techniques to study the mycobacteria has advanced greatly
      since the first genomic libraries of Mycobacterium tuberculosis and M. leprae
      were constructed in 1985. However, there are still pitfalls for the unwary. Most
      of the problems associated with the use of molecular techniques to study
      mycobacteria can be related to one of the following problems: slow growth rate
      causing problems with contamination; the formation of macroscopic clumps when
      grown in culture; resistance to standard chemical lysis procedures; the
      requirement for containment facilities for pathogenic species; the lack of
      suitable genetic vectors; and the problems of spontaneous antibiotic resistance.
      Despite these problems, considerable progress has been made and standard
      techniques have been developed for the preparation of protein, nucleic acids (DNA
      and RNA) and cell wall components, chemical and transposon mutagenesis and gene
      replacement methods, the use of reporter genes and expression vectors, and
      improved detection and drug sensitivity testing.

PMID- 10934533
TI  - Protein-protein interactions in signaling cascades.
AB  - The process of signal transduction is dependent on specific protein-protein
      interactions. In many cases these interactions are mediated by modular protein
      domains that confer specific binding activity to the proteins in which they are
      found. Rapid progress has been made in the biochemical characterization of
      binding interactions, the identification of binding partners, and determination
      of the three-dimensional structures of binding modules and their ligands. The
      resulting information establishes the logical framework for our current
      understanding of the signal transduction machinery. In this overview a variety of
      protein interaction modules are discussed, and issues relating to binding
      specificity and the significance of a particular interaction are considered.

PMID- 10934534
TI  - Time-resolved fluoroimmunoassay.
AB  - A method is reported to set up a standard competitive TR-FIA. A simple and
      inexpensive way to prepare reagents and carry out operations is presented as
      well, with the aim to make it possible to perform a very sensitive analytical
      procedure in a personalized way within a nondedicated biochemistry laboratory.
      This protocol is general and can be easily modified with consideration to the
      analytical target. Once the antibody is available, both its labeling with
      diethylenetriaminepentaacetic acid dianhydride and Eu3+, and the setting-up of
      the assay with measurement of europium ion time-resolved fluorescence in a home
      made enhancement solution become feasible.

PMID- 10934536
TI  - Direct and indirect methods of measuring Helicobacter pylori drug susceptibility
      in vitro.
AB  - This article outlines a number of methods for the determination of inhibitory and
      bactericidal activity against H. pylori. Direct methods rely on the ability of
      bacteria to divide and multiply and ultimately form visible colonies after
      subjection to antibiotic treatment. Indirect methods rely on the measurement of
      metabolic activity as a viability marker and are much more rapid, especially
      taking into account the slow growth and fastidious nature of the organism.
      Inhibitory concentration measurement does not indicate the bactericidal ability
      of a drug; inhibition of growth does not necessarily correlate with cell death.
      Theoretical generation of viable but nonculturable bacteria could bring in to
      question the validity of direct measurements based on the colony forming ability
      of an organism posttreatment.

PMID- 10934535
TI  - Recombinant vaccinia viruses. Design, generation, and isolation.
AB  - The technologies of recombinant gene expression have greatly enhanced the
      structural and functional analyses of genetic elements and proteins. Vaccinia
      virus, a large double-stranded DNA virus and the prototypic and best
      characterized member of the poxvirus family, has been an instrumental tool among
      these technologies and the recombinant vaccinia virus system has been widely
      employed to express genes from eukaryotic, prokaryotic, and viral origins.
      Vaccinia virus is also the prototype live viral vaccine and serves as the basis
      for well established viral vectors which have been successfully evaluated as
      human and animal vaccines for infectious diseases and as anticancer vaccines in a
      variety of animal model systems. Vaccinia virus technology has also been
      instrumental in a number of unique applications, from the discovery of new viral
      receptors to the synthesis and assembly of other viruses in culture. Here we
      provide a simple and detailed outline of the processes involved in the generation
      of a typical recombinant vaccinia virus, along with an up to date review of
      relevant literature.

PMID- 10934537
TI  - Member risk adjustment for ambulatory episodes of care.
AB  - The purpose of this study was to model health-plan member risk based on member
      characteristics in order to separate member risk from other utilization
      determinants for the use of health care services across sites of care. The
      approach was to build episodes of care (EOCs) by sorting one year of
      encounter/claims data into Common Treatment Categories (CTCs). These data came
      from a variety of health plans, both capitated and non-capitated, covering over 2
      million lives. The EOCs were characterized by an array of event and intensity
      measures. Episode-level risk for each of these measures was modeled by
      regressions based on member demographic and clinical characteristics. The results
      of this study show that member characteristics explain a substantial amount of
      event and intensity variation within episodes and that no single performance
      measure can summarize the care of health plan members. This method for evaluating
      member risk can be used both to stratify members according to their future risk
      and potentially to assess provider or health plan performance or to adjust
      reimbursement for performance or risk selection.

PMID- 10934538
TI  - The quick response initiative in the emergency department: who benefits?
AB  - OBJECTIVES: This collaborative project between two community hospitals, a
      Metropolitan Home Care Program and the University, was designed to quantify the
      applicability (who is eligible for) and acceptability (who will likely comply
      with) Home Care services, provided through a Quick Response Program (QRP)
      initiative as compared to usual hospital care services, to patients, families and
      physicians. METHODS: During a 6 week period of sampling (5 days per week, 8 hours
      per day) in two Emergency Departments (ED) in moderately sized community
      hospitals in a major metropolitan city, all patients triaged to the urgent
      category were assessed for eligibility for QRP services by on-site Home Care
      Coordinators using specific criteria. Patients meeting the criteria initially
      were reviewed by the ED physician for approval for QRP services and then
      randomized to experimental and control conditions. Patients not meeting the
      eligibility criteria were managed by the usual ED services procedures.
      Demographic and clinical data were obtained on all urgent category patients at
      presentation to the ED. Additionally, the nature and cost of all health care
      services used by the ED patients during the ED event and 10 days follow up, were
      obtained through hospital and Home Care record abstraction and compared among the
      different sample groups. RESULTS: The QRP Initiative was applicable to 2% of the
      total ED patient population and 5% of the urgent category of patients triaged in
      the ED. It was acceptable to 97% of this eligible group. One hundred and fifty
      five patients who initially qualified for QRP were excluded from eligibility at a
      subsequent assessment. Ninety of these patients were admitted to hospital and 65
      were discharged home. In the total "exclusion" group, 37 refused Home Care
      services including the QRP. HEALTH CARE PRACTICE IMPLICATIONS: The sampling
      results raise important questions about broader system issues concerning the role
      of the hospital and community in providing health care services and the social
      value or utility that guides the allocation of health care funds. What level of
      applicability and acceptability would justify priority services for certain
      target groups. In the future, policy makers will need to be able to show that it
      is in the best interest of patients and society to prioritize mixtures of
      services to certain target groups.

PMID- 10934539
TI  - Predictors of Medicare costs in elderly beneficiaries with breast, colorectal,
      lung, or prostate cancer.
AB  - BACKGROUND: Determining the apportionment of costs of cancer care and identifying
      factors that predict costs are important for planning ethical resource allocation
      for cancer care, especially in markets where managed care has grown. DESIGN: This
      study linked tumor registry data with Medicare administrative claims to determine
      the costs of care for breast, colorectal, lung and prostate cancers during the
      initial year subsequent to diagnosis, and to develop models to identify factors
      predicting costs. SUBJECTS: Patients with a diagnosis of breast (n = 1,952),
      colorectal (n = 2,563), lung (n = 3,331) or prostate cancer (n = 3,179) diagnosed
      from 1985 through 1988. RESULTS: The average costs during the initial treatment
      period were $12,141 (s.d. = $10,434) for breast cancer, $24,910 (s.d. = $14,870)
      for colorectal cancer, $21,351 (s.d. = $14,813) for lung cancer, and $14,361
      (s.d. = $11,216) for prostate cancer. Using least squares regression analysis,
      factors significantly associated with cost included comorbidity, hospital length
      of stay, type of therapy, and ZIP level income for all four cancer sites. Access
      to health care resources was variably associated with costs of care. Total R2
      ranged from 38% (prostate) to 49% (breast). The prediction error for the
      regression models ranged from < 1% to 4%, by cancer site. CONCLUSIONS: Linking
      administrative claims with state tumor registry data can accurately predict costs
      of cancer care during the first year subsequent to diagnosis for cancer patients.
      Regression models using both data sources may be useful to health plans and
      providers and in determining appropriate prospective reimbursement for cancer,
      particularly with increasing HMO penetration and decreased ability to capture
      complete and accurate utilization and cost data on this population.

PMID- 10934540
TI  - Efficiency measurement of health care: a review of non-parametric methods and
      applications.
AB  - There has been increasing interest in measuring the productive performance of
      health care services, since the mid-1980s. This paper reviews this literature
      and, in particular, the concept and measurement of efficiency and productivity.
      Concerning measurement, we focus on the use of Data Envelopment Analysis (DEA), a
      technique particularly appropriate when multiple outputs are produced from
      multiple inputs. Applications to hospitals and to the wider context of general
      health care are reviewed and the empirical evidence from both the USA and Europe
      (EU) is that public rather than private provision is more efficient.

PMID- 10934541
TI  - Estimating the prevalence of injecting drug users on the basis of Markov models
      of the HIV/AIDS epidemic: applications to Italian data.
AB  - This paper addresses some important issues related to the estimation of the
      extent of injecting drug use. The population of injecting drug (heroin) users in
      Italy is estimated on the basis of a dynamic model of the health consequences, in
      particular using AIDS incidence data. The use of the prevalence estimates to
      monitor the impact of health care and law enforcement interventions is outlined.

PMID- 10934542
TI  - Decision support for malaria-control programmes--a system dynamics model.
AB  - Although malaria claims millions of casualties every year there are hardly any
      recent efforts to model its epidemiology in order to support decision-makers of
      malaria-control programmes. There have been ample attempts to develop analytical
      models during the era of WHO malaria eradication programmes (1950-1970), but none
      of them was detailed enough to honour the high complexity arising from the
      interdependencies of the environment, the parasite, vector and host system. This
      paper presents a multi-group system dynamics model of the spread of malaria in an
      African country. Epidemiological details are included so that the impact of
      several intervention programmes can be simulated and analysed. The model's basic
      structure is fully described and some examples of the simulations are presented.
      It becomes obvious that detailed multi-group system dynamics models are valuable
      to assess the effectiveness and efficiency of anti-malaria campaigns.

PMID- 10934543
TI  - Is uterine cervical cancer a potentially preventable sexually transmitted
      disease?

PMID- 10934544
TI  - In vitro susceptibility of Plasmodium falciparum to four antimalarial drugs in
      the Central Province of Papua New Guinea.
AB  - The susceptibility of Plasmodium falciparum to chloroquine, quinine, mefloquine
      and halofantrine was investigated in the Central Province of Papua New Guinea
      between March 1995 and September 1996, when chloroquine resistance was widely
      present in the country. The standard World Health Organization in vitro microtest
      methodology was used in the study. Of the 30 isolates tested for chloroquine
      susceptibility all were resistant to chloroquine with median IC50 of 1.15 mumol/l
      (range 0.54 to 4.24), indicating a high prevalence and degree of resistance.
      Three isolates each for quinine (3/31) and halofantrine (3/28) showed resistance
      at concentrations of 51.2 mumol/l and 10 nM respectively, while all 31 isolates
      tested for mefloquine were fully susceptible. The comparative analysis of median
      IC50 values between isolates resistant and susceptible to chloroquine showed
      chloroquine-resistant isolates to be less susceptible to quinine and halofantrine
      while fully susceptible to mefloquine. It seems that the evolution of chloroquine
      resistance together with increased use of quinine treatment of P. falciparum
      malaria may increase the risk of emergence of quinine resistance and possibly of
      halofantrine resistance as well. The development of mefloquine resistance,
      however, is independent of chloroquine resistance.

PMID- 10934546
TI  - Hypertension among adults of the Purari delta of the Gulf Province, Papua New
      Guinea.
AB  - This study, carried out in 1995, found evidence of high blood pressure in a rural
      population in the Gulf Province of Papua New Guinea. Although the prevalence of
      obesity as assessed by the body mass index has increased since 1980, blood
      pressure was not associated with height or weight. Rather, it was associated with
      fat patterning: increased truncal fatness was associated with greater systolic
      blood pressure in both males and females. Of the modernization variables
      examined, the only one associated with blood pressure was type of income, and
      this for systolic blood pressure among females only. Body mass index was also
      associated with type of income, this being greatest among the small number of
      adults with some form of paid employment. Blood pressure showed no association
      with age, thus conforming to the hypertension pattern seen at early stages of
      modernization.

PMID- 10934545
TI  - A study of the correlation of prostatic pathology and serum prostate-specific
      antigen (PSA) levels: a perspective from Papua New Guinea.
AB  - A review of serum prostate-specific antigen (PSA) values from January 1994 to May
      1997 and their correlation with the histopathology of prostate specimens was
      carried out in the Department of Pathology, Port Moresby General Hospital. The
      study has shown that this biochemical investigation has not been properly used
      for the maximum benefit of the patient population. Remedial measures are
      suggested to improve the sensitivity and specificity of PSA in a setting with
      limited resources.

PMID- 10934547
TI  - Tuberculosis control in Papua New Guinea.

PMID- 10934549
TI  - Meckel-Gruber syndrome: report of an affected Papua New Guinean family.
AB  - We present the first case report of a Papua New Guinean family affected by Meckel
      Gruber syndrome. Of six children, five of whom died, three definitely and two
      possibly were affected.

PMID- 10934548
TI  - Multiple liver abscesses: an unusual case which demonstrates the importance of
      ultrasonography in the detection of liver pathology.
AB  - A 48-year-old caucasian male was admitted to hospital with right-sided chest
      pain, pyrexia and cough. He had no history of dysentery. He was treated with
      erythromycin and cotrimoxazole for right lower lobe pneumonia but failed to
      respond. Tender hepatomegaly developed and ultrasound scan demonstrated multiple
      abscesses in the liver. Entamoeba histolytica was identified in his faeces. He
      was treated with intravenous metronidazole, chloramphenicol and gentamicin and
      then oral tinidazole, after which improvement was rapid. He was later transferred
      to Australia. Subsequent abdominal CAT scan and aspiration of abscesses confirmed
      the diagnosis of multiple amoebic liver abscesses with secondary bacterial
      infection. Final treatment was with oral ciprofloxacin and metronidazole for four
      weeks. Ultrasonography is a noninvasive technique which is invaluable in the
      diagnosis of abdominal and especially liver pathology. This technique should be
      available in larger centres in tropical countries. Anyone living in or visiting
      the tropics should be aware of possible exotic diseases presenting in unusual
      ways.

PMID- 10934550
TI  - The public health imperative in Papua New Guinea.

PMID- 10934552
TI  - Halofantrine versus quinine-Fansidar combination in the treatment of post
      chloroquine falciparum parasitaemia.
AB  - The standard first-line treatment for malaria in adults in Papua New Guinea is
      chloroquine; for severe and treatment-failure malaria standard therapy is a
      combination of quinine and Fansidar (sulphadoxine-pyrimethamine). These standard
      treatments are currently under revision. The present study evaluated the effect
      of halofantrine in treatment-failure falciparum malaria in adults in Port Moresby
      compared to standard therapy. In the halofantrine group all parasites were
      cleared by day 5 after starting therapy, in the quinine-Fansidar group by day 7.
      There was no evidence of recurrence of parasitaemia during the 21-day follow-up
      in either group. Nausea was associated with halofantrine use in 68% of patients.
      In the quinine-Fansidar group 79% had muffled deafness, 32% tinnitus and 26%
      dizziness; 32% of patients withdrew from treatment on day 2 because of
      intolerance to quinine. Halofantrine in this study population provided an
      efficacy against treatment-failure falciparum malaria similar to that of quinine
      Fansidar, with a more favourable profile of adverse effects.

PMID- 10934553
TI  - Plasmodium ovale species in Papua New Guinea--lest we forget.
AB  - The microscopical diagnosis of Plasmodium ovale infection is reviewed and its
      similarity to Plasmodium vivax emphasized. Its presence in Papua New Guinea has
      been recognized for many years, from a time not long after Stephens first
      described the species in 1922, but it is rarely reported. There is no doubt of
      its presence in Papua New Guinea, together with P. falciparum, P. vivax and P.
      malariae, but its exact prevalence and distribution has not been determined.

PMID- 10934554
TI  - Antenatal haemoglobin profile at the Port Moresby General Hospital.
AB  - From 1 November 1995 to 10 April 1996, 1001 consecutive mothers who had attended
      the Port Moresby General Hospital (PMGH) antenatal clinic and were delivered in
      the Maternity Unit of the PMGH were surveyed for their antenatal haemoglobin (Hb)
      levels. One or more Hb results had been noted in the antenatal records of 997
      subjects. The mean of the first Hb level for this sample was 10.6 +/- 1.72 g/dl.
      The first Hb level was below 10.0 g/dl in 33% of the 997 subjects. The dates were
      reliable in 777 subjects. The mean first Hb for this group was the same as for
      the total sample. A subgroup of 449 subjects with reliable dates and first Hb
      measurement at < or = 26 weeks gestation had a first Hb mean of 10.9 +/- 1.78
      g/dl. Among those with reliable dates, 569 had two or more Hb measurements, the
      last being at > or = 34 weeks. In this subgroup, the mean of the last Hb was 11.1
      +/- 1.60 g/dl. The first Hb was measured at < or = 26 weeks in 352 subjects in
      this subgroup. The means for the first and last Hb levels for this subset were
      10.9 +/- 1.78 and 11.1 +/- 1.57 g/dl, respectively; the paired t test did not
      show any difference between the first and last Hb levels. For subjects in the
      total sample who had two or more Hb measurements, the mean for the lowest Hb
      level was 10.0 +/- 1.54; 45% had levels below 10.0 g/dl at some time during the
      pregnancy.

PMID- 10934551
TI  - Safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine
      (PedvaxHIB) in Papua New Guinean children.
AB  - BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae
      type b (Hib) in young Papua New Guinean children, the incorporation of a Hib
      conjugate vaccine into a nationwide immunization program would be of major public
      health benefit. The choice of the Hib conjugate vaccine will be based on the
      evaluation of several Hib conjugate vaccines, after consideration of such factors
      as the ease of incorporation into the current vaccination schedule, cost,
      kinetics of antibody responses and safety. METHODS: This study evaluated the
      safety and immunogenicity of Hib polysaccharide-Neisseria meningitidis outer
      membrane protein complex conjugate vaccine (PRP-OMPC) in Papua New Guinea. 95
      children were recruited at Goroka Base Hospital, Eastern Highlands Province, and
      enrolled in the study. PRP-OMPC was administered at ages 2, 4 and 12 to 15
      months. Blood was collected before each dose, one month after the second and
      booster doses, and at ages 18 and 24 months. Antibody to PRP (anti-PRP) was
      measured by radioimmunoassay. RESULTS: PRP-OMPC was generally well tolerated. At
      successive sampling times from the prevaccination bleed through the 1-month post
      booster bleed, geometric mean titres were 0.18, 1.45, 2.54, 1.03 and 8.05
      micrograms/ml, respectively (n = 60). The proportions of subjects with anti-PRP
      titres > or = 1.0 microgram/ml were 2%, 62%, 73%, 47% and 93%, respectively (n =
      60). Persistence of anti-PRP was ascertained in 41 subjects. The GMTs at 18 and
      24 months were 3.42 and 2.0 micrograms/ml, respectively. CONCLUSIONS: PRP-OMPC
      was found to be immunogenic after the first dose and to elicit a robust booster
      response. Antibody titres persisted until age 24 months, at which time 100% of
      subjects had anti-PRP > or = 0.15 microgram/ml. These results are consistent with
      previous studies in US Native American infants and in Gambian infants.

PMID- 10934555
TI  - A case-control study of stillbirths at the Port Moresby General Hospital.
AB  - From September 1995 to May 1997, 315 consecutive stillbirths and 315 randomly
      selected controls were studied at the Port Moresby General Hospital to determine
      the causes of the deaths, to describe the sociodemographic and reproductive
      characteristics of the mothers, and to see if there were any avoidable factors in
      the stillbirths and where the responsibility for them lay. 249 (79%) of the
      stillbirths were antepartum and 14% were intrapartum; the timing of death could
      not be determined in the remaining 21 (7%). 36% of the stillbirths were
      unexplained. The common identified causes were: syphilis (VDRL and TPHA positive)
      10%, intrauterine growth restriction/placental insufficiency 9%, antepartum
      haemorrhage 9%, malaria 6%, major congenital abnormalities 6%, cord accidents 6%,
      pregnancy-induced hypertension 5% and acute intrapartum asphyxia 4%. Multiple
      logistic regression analysis showed a significant association between stillbirth
      and the following variables: husband's occupation unskilled, age over 35 years,
      poor antenatal attendance, a past history of stillbirth, syphilis and malaria. An
      avoidable factor was established in 41% of the cases; in 60% the responsibility
      for the avoidable factor lay with the patient and her relatives.

PMID- 10934556
TI  - X-ray survey for pulmonary tuberculosis and chest diseases in the Ok Tedi region
      of Western Province, Papua New Guinea.
AB  - X-ray photofluorography is a relatively expensive way to detect pulmonary
      tuberculosis (PTB). Those patients with suggestive positive chest X-ray still
      require Mantoux skin testing, blood tests and a positive sputum smear for the
      acid-fast bacillus Mycobacterium tuberculosis to make a definitive diagnosis of
      PTB. Photofluorography does detect most pulmonary pathological conditions,
      including lesions suggestive of PTB, and possible cardiac abnormalities. It is
      more cost-effective for large numbers in urban areas where there is poverty and
      overcrowding; and it is useful in early detection of cases of PTB. It is
      impractical to use in the isolated mountainous areas in the highlands region of
      Papua New Guinea and in Western Province, and where there is no road system. It
      cannot detect other forms of TB. In children and infants it is difficult to
      obtain good quality films and to interpret them. The scoring chart devised by
      Biddulph and Edwards is an excellent alternative where a diagnosis is not obvious
      in a chronically ill child. Active case detection by health workers in the field
      offers an excellent chance of finding TB cases. Although the cost of staining and
      looking at sputum smears and performing Mantoux tests can also be time consuming,
      these methods are relatively less expensive and more accurate. A simple method of
      processing sputum before Ziehl-Neelsen staining using ordinary household bleach
      vastly improves the detection rate of acid-fast bacilli. The new technology of
      demonstrating positive TB antigens in the blood of patients with active disease
      is still being assessed.

PMID- 10934557
TI  - Molecular genetics of Alzheimer's disease: what have we learned?
AB  - Alzheimer's disease (AD), by far the most common form of dementia in the elderly,
      is clinically characterized by gradual, progressive loss in cognitive functioning
      and changes in personality, ultimately leading to death. It is now well
      established that genetic factors play an important role in AD. So far, three
      genes have been identified in which mutations cause autosomal-dominant AD: the
      amyloid precursor protein (APP) gene on chromosome 21, the presenilin 1 (PSEN1)
      gene on chromosome 14, and the homologous presenilin 2 (PSEN2) gene on chromosome
      1. A major susceptibility gene, the apolipoprotein E (APOE) gene, was identified
      on chromosome 19.

PMID- 10934558
TI  - Mechanisms of functional restoration after brain injury.
AB  - The mechanisms accounting for clinical improvement after brain injury are still a
      matter of debate. Better knowledge of the recovery process is important for it
      might be influenced by therapy. This article reviews a number of studies devoted
      to the physiopathology of recovery from aphasia and visuo-spatial neglect after
      the acute stage, using various methods (cerebral blood flow and metabolism
      measurements, dichotic listening, transcranial Doppler ultrasonography,
      functional magnetic resonance imaging) with special reference to the contribution
      of methods using activation procedures.

PMID- 10934559
TI  - Demographic characteristics and prognosis in a Flemish amyotrophic lateral
      sclerosis population.
AB  - We describe the genetic and demographic characteristics of patients with
      amyotrophic lateral sclerosis (ALS) in Flanders, Belgium. Prognostic factors
      related to survival are examined. ALS was familial in 8.6% of all MND patients.
      In 6 of 8 apparently unrelated families, an SOD1 mutation was found. In sporadic
      ALS, mean age at onset was 57.1 years. There was a male preponderance (1.2:1) and
      the disease had a bulbar onset in 19%. Median survival was 32 months (95% CI 26
      46). The presence of an APOE-epsilon 4 allele was not associated with a bulbar
      onset of ALS, an earlier age at onset or a shorter median survival. Variables
      examined in a multivariate analysis included age, sex, site of onset, delay from
      onset to diagnosis, and % forced vital capacity. Shorter survival was
      independently associated with higher age, bulbar onset, a short diagnostic delay,
      and a lower percent-predicted vital capacity at study entry. Simple clinical
      baseline characteristics can assist the clinician in estimating prognosis in ALS.
      The demographic characteristics of the Flemish ALS population do not seem to
      differ from those described in other parts of the world.

PMID- 10934561
TI  - The three responses of the blink reflex in adult and juvenile migraine.
AB  - Recent theories about migraine pathogenesis have emphasized the role of the
      trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The
      blink reflex (BR) could be a suitable method to evaluate the trigeminal system in
      migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic
      division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and
      15 juvenile migraine without aura subjects were selected, in order to evaluate
      the BR features, including the subjective perceptive and pain thresholds and the
      R1, R2 and R3 components intensity thresholds and amplitudes. The
      electrophysiological procedure was carried out during the pain free phase. The
      findings were compared with those of 28 healthy controls, 18 adults and 10
      children. In both adult and juvenile migraine sufferers an early appearance of
      the R3 response at almost the R2 threshold was observed in comparison with age
      matched controls. Unfortunately, the anatomic and physiologic organization of the
      R3 component is uncertain: its early onset could suggest a dysfunction of the
      inhibitory control system on the trigeminal networks, which may predispose to
      migraine attacks.

PMID- 10934560
TI  - Neuropraxia of the cervical spinal cord following cervical spinal cord trauma: a
      report of five patients.
AB  - Neuropraxia of the cervical spinal cord is a rare condition which is almost
      exclusively reported in American football players following cervical
      hyperextension or hyperflexion trauma. In this entity-neurological symptoms of
      both arms and legs for a period of up to 15 minutes are observed with complete
      recovery. We report the characteristics of five patients not involved in contact
      sport activities with a neuropraxia of the spinal cord following cervical trauma.
      In four of the five patients, this syndrome was associated with a cervical canal
      stenosis. Surgical decompression was performed in two patients with progressive
      neurological symptoms after an initial period of recovery. The cases illustrates
      that although neuropraxia of the spinal cord is usually seen in athletes, also
      other persons may be at risk for developing this condition, especially when a
      preexisting spinal stenosis is present. Patients who experienced neuropraxia of
      the spinal cord should thus be evaluated carefully for the presence of cervical
      spinal cord abnormalities.

PMID- 10934562
TI  - Isolated bilateral abducens nerve palsy in primary sphenoidal sinus non-Hodgkin
      lymphoma.
AB  - Isolated bilateral abducens nerve palsy is a rare complication of intracavernous
      tumors. A middle-aged man complaining of chronic horizontal diplopia was found to
      have bilateral abducens palsy as an initial manifestation of a massive non
      Hodgkin lymphoma, originating from the sphenoidal sinus. This case is unique in
      two respects: the initial clinical presentation of isolated bilateral abducens
      involvement and the nature of the tumor, since only two cases of sphenoidal sinus
      lymphoma have been reported.

PMID- 10934563
TI  - Usefulness of gait analysis combined with motor point block in a stroke patient.
AB  - This clinical note describes a typical case of dynamic varus deformity of the
      rear foot in a stroke patient. An overactive Tibialis Posterior muscle seemed
      mainly responsible for the varus deformity. However, this hypothesis was not
      confirmed by a motor point block of this muscle. It appeared that the Tibialis
      Posterior and Extensor Hallucis Longus muscles were both involved in the varus
      deformity. A double motor point block of both the Tibialis Posterior and Extensor
      Hallucis Longus muscles was performed. Kinematic and kinetic data showed
      improvement. This case report illustrates the usefulness of gait analysis
      combined with motor point block in the diagnosis and management of gait
      disturbance.

PMID- 10934565
TI  - Sudden unexpected death in epilepsy in adults with mental retardation.
AB  - The medical records of residents of a facility for persons with mental
      retardation from January 1, 1978, through December 31, 1997, were analyzed to
      identify incidence of sudden unexpected death for groups of 180 individuals with
      and 125 without comorbid epilepsy. Eighty deaths were identified, with 55
      occurring in the epilepsy group and 25 in the nonepilepsy group. The rate of
      sudden unexpected death was 1.3 deaths per 1,000 patient years in the nonepilepsy
      group and 3.6 deaths per 1,000 patient years in the epilepsy group. The risk
      factors for sudden unexpected death in the epilepsy group were nonambulatory
      status and poorly controlled seizure disorder (increased seizure rate and
      increased number of antiepileptic drugs).

PMID- 10934564
TI  - Hypertrophic olivary degeneration.

PMID- 10934566
TI  - Patterns of behavioral adjustment and maladjustment in mental retardation:
      comparison of children with and without ADHD.
AB  - A variety of behavioral and emotional problems have been associated with
      attention deficit disorder with hyperactivity (ADHD) in children of average
      intellect. In contrast, little is known about concomitant behavioral and
      emotional problems in children with ADHD and mental retardation. In this study,
      we used the Personality Inventory for Children-Revised to assess the behavioral
      adjustment of 48 children with mental retardation and ADHD compared to that of 47
      children with mental retardation without ADHD. The ADHD group had significantly
      more symptoms of depression, family conflict, noncompliance, anxiety,
      hyperactivity, inadequate social skills, and academic problems. Results are
      strongly suggestive of significant behavioral and emotional problems in children
      with ADHD and mental retardation, thus mirroring the pattern associated with ADHD
      in the general school-age population.

PMID- 10934567
TI  - Comparing parent and teacher ratings of social competence and problem behaviors.
AB  - A comparison between parent and teacher ratings of 109 school children on the
      French version of the Nisonger Child Behavior Rating Form, which measures social
      competence and problem behaviors of children with developmental disabilities, was
      conducted. Results indicated no significant differences between parent and
      teacher ratings on the two social competence subscales and two problem behavior
      subscales. Ratings differed significantly on three problem behavior subscales:
      (a) Conduct Problem, (b) Insecure/Anxious, and (c) Hyperactive. These results may
      be indicative of complementary information according to the context (home vs.
      school). Also, results support the premise that it is important to collect
      information from multiple sources in order to obtain a complete and global
      assessment of the child's problem behavior/psychopathology.

PMID- 10934568
TI  - Dynamics of lip dyskinesia associated with neuroleptic withdrawal.
AB  - The lip movements associated with dyskinesia in adults with mental retardation
      were investigated through a dynamic analysis at medication baseline, at the
      points of the highest level of withdrawal dyskinesia as indexed by the DISCUS
      rating scale, and at the lowest level of dyskinesia following complete withdrawal
      of the medication. Results showed that the changes in the amount of lip
      oscillations following medication reduction and eventual withdrawal were strongly
      linked to changes in the structural complexity of the dynamics of lip motions.
      These findings provide evidence that neuroleptic medication reduces the df of the
      dynamics of the movement output and that this change is inversely related to the
      level of tardive dyskinetic motion observed in the clinical setting.

PMID- 10934569
TI  - Randomized trial of intensive early intervention for children with pervasive
      developmental disorder.
AB  - Young children with pervasive developmental disorder were randomly assigned to
      intensive treatment or parent training. The intensive treatment group (7 with
      autism, 8 with pervasive developmental disorder not otherwise specified--NOS)
      averaged 24.52 hours per week of individual treatment for one year, gradually
      reducing hours over the next 1 to 2 years. The parent training group (7 with
      autism, 6 with pervasive developmental disorder NOS) received 3 to 9 months of
      parent training. The groups appeared similar at intake on all measures; however,
      at follow-up the intensive treatment group outperformed the parent training group
      on measures of intelligence, visual-spatial skills, language, and academics,
      though not adaptive functioning or behavior problems. Children with pervasive
      developmental disorder NOS may have gained more than those with autism.

PMID- 10934570
TI  - Early behavior signs of psychiatric phenotypes in fragile X syndrome.
AB  - Whether preschool males with fragile X syndrome can be distinguished from those
      with idiopathic developmental delay in the four problem behavior areas associated
      with the fragile X phenotypes was examined. Males with fragile X (n = 41) and age
      and IQ-matched controls (n = 16) were rated by their mothers on the Dimensions
      of Temperament Scale-Revised, the Child Behavior Checklist, and the Aberrant
      Behavior Checklist--Community. The fragile X group showed deficits in motor
      skills, increased initial avoidance, decreased social withdrawal, deficits in
      attention, increased hyperactivity, and positive mood. They were distinguished
      from controls on all of these variables except hyperactivity and attention. When
      maternal characteristics were controlled for, the fragile X group showed a
      significantly higher level of generalized activity level than did controls.

PMID- 10934571
TI  - Behavior states are real and observable.
AB  - Mudford, Hogg, and Roberts (1999) published additional concerns about their
      failure to achieve interobserver agreement on adults with mental retardation when
      using an experimental, 13-category behavior state code we earlier provided to
      them at their request. They presented findings of interobserver agreements from a
      videotape of their 3 adult participants that was scored by observers at the
      University of Kansas. In this response we present extensive investigations
      demonstrating the reliable measurement of behavior state among infants and adults
      with mental retardation, including independent data from other state researchers.
      We give arguments showing why their "videotape study" does not meet requirements
      for acceptable research methodology and discuss other procedural issues for
      measuring state behavior among infants with and those without disabilities.

PMID- 10934572
TI  - Genetics of the risk for alcoholism.
AB  - This paper reviews the literature on the importance of genetic influences in the
      development of alcohol abuse and dependence (alcoholism). The alcohol use
      disorders are fairly typical of most complex genetic conditions in that multiple
      genetic influences combine together to explain approximately 40% to 60% of the
      risk. One useful approach for identifying specific genes related to alcoholism
      involves identifying a population in which known genetic factors are controlled
      and using genome scan and/or case-control, association approaches to search for
      specific genes. Several characteristics, or endophenotypes, have been identified
      as both genetically influenced and contributing toward the risk for alcoholism,
      including alcohol-metabolizing enzymes, the low level of response to alcohol, and
      electrophysiological measures. The potential importance of each of these
      characteristics is reviewed, and data relating to the search for specific genetic
      material for each endophenotype are presented. These findings are placed in the
      perspective of the impact that they are likely to have on both prevention and
      treatment efforts in the alcohol field.

PMID- 10934573
TI  - Substance dependence and other psychiatric disorders among drug dependent
      subjects: race and gender correlates.
AB  - Persons in drug treatment with drug dependence were interviewed with the NIMH
      Diagnostic Interview Schedule to ascertain DSM-III-R disorders. Lifetime
      prevalence rates were 64% for alcohol dependence, 44% for antisocial personality
      disorder (ASPD), 39% for phobic disorders, 24% for major depression, 12% for
      dysthymia, 10% for generalized anxiety disorder, 3% for panic disorder, 3% for
      mania, 3% for obsessive compulsive disorder, 2% for bulimia, 1% for
      schizophrenia, and 1% for anorexia. When stratified by race and age, significant
      main effects were seen, but there were no significant interactions except in "any
      non-substance disorder" and in the mean number of non-substance use disorders.
      Caucasians had a higher mean number of drug dependence disorders and higher
      overall rates of "any other" disorder than African-Americans, and Caucasians and
      males had higher mean numbers of non-substance use disorders than African
      Americans and females, respectively. This was related to rates of alcohol,
      cannabis, and hallucinogen dependence, and ASPD rates that were higher among men
      than women and higher among Caucasian respondents than African-American for
      alcohol, cannabis, hallucinogen, opiate and sedative dependence, major
      depression, dysthymia, and generalized anxiety disorder. In contrast, women had
      higher rates than men of amphetamine dependence, phobic disorder, major
      depression, dysthymia, panic disorder, obsessive compulsive disorder, and mania.
      African-Americans had higher rates than Caucasians of amphetamine, cocaine, and
      phencyclidine dependence, but for no comorbid disorders were the rates higher
      among African-Americans than Caucasians. The differences according to gender in
      rates of disorders among substance dependent persons are consistent with the
      results of general population surveys, but the differences in rates according to
      race are in contrast to these same community surveys. Limitations in the utility
      of the concept of race as a valid category diminish the generalizability of the
      findings; however, one possible explanation is differential treatment seeking in
      African-American and Caucasian populations that would result in the differences
      seen.

PMID- 10934574
TI  - Psychiatric disorders among drug dependent subjects: are they primary or
      secondary?
AB  - The relationship between substance use disorders and comorbid psychiatric
      conditions was investigated among 425 persons in drug treatment who met DSM-III-R
      criteria for drug dependence. Using the NIMH Diagnostic Interview Schedule to
      ascertain DSM-III-R psychiatric disorders among these drug dependent subjects,
      lifetime prevalence rates were 64% for alcohol abuse/dependence, 44% for
      antisocial personality disorder, 39% for phobic disorders, 24% for major
      depression, 12% for dysthymia, and 10% for generalized anxiety disorder. We found
      that antisocial personality disorder and phobias generally had onsets prior to
      the onset of drug dependence (that is, they were primary disorders). The majority
      of drug dependent persons with generalized anxiety disorder reported an onset
      after the onset of drug dependence (that is, they had secondary generalized
      anxiety). Alcohol dependence, depression, and dysthymia were divided nearly
      evenly between earlier (primary disorder) and later (secondary disorder). These
      results are consistent with the body of literature indicating the importance of
      antisocial syndromes in the etiology of substance abuse and the literature
      indicating the complex, varying nature of the relationship of psychiatric
      disorders to substance dependence. Finally, a precise nomenclature for "age of
      onset," "primary," and "secondary" was developed for this study that is critical
      to understanding these issues and is recommended for other studies.

PMID- 10934575
TI  - Routine hospital alcohol detoxification practice compared to symptom triggered
      management with an Objective Withdrawal Scale (CIWA-Ar).
AB  - Charts of patients hospitalized for uncomplicated alcohol withdrawal were
      examined and detoxification practices compared. Patients detoxified using a
      Clinical Institute Withdrawal Assessment for Alcohol-revised (CIWA-Ar) based PRN
      protocol on the addiction unit received significantly fewer chlordiazepoxide
      milligram equivalents over shorter duration than patients managed by other
      detoxification methods on other hospital units. Significantly fewer patients
      received benzodiazepines in the CIWA-Ar protocol managed group, but inter-group
      differences (p < 0.01) remained when only medicated patients were compared.
      Differences between the protocol and non-protocol groups did not reach
      statistical significance when PRN only strategies were examined, suggesting that
      the use of a symptom-triggered strategy may account for the noted effects.

PMID- 10934576
TI  - The effect of stimulant and sedative use on treatment outcome of patients
      admitted to methadone maintenance treatment.
AB  - While methadone maintenance treatment (MMT) has been demonstrated to be an
      effective treatment for opiate dependence, its impact on the treatment outcome of
      other illicit drug abuse is not as clear. Using the initial urine drug screen
      (UDS) and follow-up UDS at 1, 6, 12, and 24 months, 167 patients consecutively
      admitted to MMT were evaluated for opiate, sedative (predominantly
      benzodiazepine), and stimulant (predominantly cocaine) use. Retention for the
      opiate only group was 97.32 days longer on average than for patients using
      opiates along with stimulants, sedatives, or both stimulants and sedatives.
      Patients abusing opiates only had the greatest decrease in drug use; however, MMT
      was also associated with decreases in cocaine and sedative use over the 24 month
      follow-up period. There was no evidence that patients "switched" their drugs of
      abuse with time in treatment. The negative impact of non-opiate drug use on
      outcome in MMT and its implications for treatment planning are discussed.

PMID- 10934577
TI  - Skin conductance hypo-responding in recently abstinent cocaine dependent
      inpatients.
AB  - Skin conductance has been used as a measure of physiological arousal in cocaine
      cue reactivity studies. In this study, skin conductance responses in recently
      abstinent (average 3.1 +/- 1.7 days) cocaine dependent inpatients (N = 30) were
      assessed. A video depicting individuals preparing and using cocaine was the cue
      stimulus. Skin conductance responses were not increased by the stimulus cue.
      Several explanations are explored that may support not using skin conductance as
      an outcome measure in recently abstinent cocaine dependent patients.

PMID- 10934578
TI  - Psychiatric symptoms in problem gambling and non-problem gambling substance
      abusers.
AB  - This study compared demographic characteristics, Addiction Severity Index (ASI)
      ratings, and psychiatric symptoms in 103 substance abusers with and without
      gambling problems. Thirty-one of the substance abusers were identified as
      probable pathological gamblers on the South Oaks Gambling Screen. Although no
      differences in demographic characteristics or ASI ratings were noted between the
      groups, subjects with a gambling problem consistently reported more psychiatric
      distress than substance abusers without a gambling problem. Specifically, they
      had increased ratings on somatization, obsessive-compulsive, interpersonal
      sensitivity, hostility, and paranoia scales. These results are discussed in terms
      of the need to identify and treat gambling problems among substance abusers.

PMID- 10934579
TI  - Heroin-related deaths in Sydney, Australia. How common are they?
AB  - The objective of this article was to determine the number of recent deaths caused
      by accidental illicit drug overdoses seen at the NSW Institute of Forensic
      Medicine, Glebe (Sydney). All Forensic cases (3559) were reviewed during the
      period July 1995-February 1997. Any that were classified as accidental illicit
      drug overdose were followed up, and demographic and toxicological data were
      collected for analysis. Our results found that one hundred and forty three
      accidental illicit drug overdoses were identified from 3359 autopsies during the
      20 month data collection period (4%). Male to female ratio was 5:1, but females
      predominated in the methadone toxicity group. Most of the cases were under 40
      years of age. Toxicological results showed that 80% of the deaths were associated
      with morphine (heroin) levels in the toxic range, although 91% had morphine
      present at some level. Only 35% of cases had significant levels of bile morphine,
      suggesting "chronic" usage. In many cases, multiple illicit substances and/or
      alcohol were thought to be important contributing factors. Cocaine was found in
      13% of cases, and all of these had morphine (heroin) in their blood. Methadone
      was found in 13% of cases, and 13/19 had toxic levels--9/19 also had morphine in
      their blood. Only two cases had amphetamines or methamphetamines in their blood.
      The authors conclude that Heroin overdose is by far the most common cause of
      accidental illicit drug overdose. Those at greatest risk are naive users and
      those who are not tolerant. There is an urgent need for increased awareness and
      further education concerning the dangers of heroin use, particularly of multiple
      drug use (including alcohol). Only about one-third of these cases appear to be
      "chronic" users.

PMID- 10934580
TI  - Immunoreactivity to cytokeratin 8/18 in patients with soluble liver antigen (SLA)
      positive autoimmune hepatitis (AIH type 3) is not sufficient for diagnostic use.
AB  - "Soluble liver antigen" (SLA) has been reported to be an infrequent but in
      certain cases a unique marker of autoimmune hepatitis, with cytokeratins 8 and 18
      as major antigenic components. Using precharacterized sera, we could confirm
      trypsin sensitivity and a molecular weight of approximately 50 kD of the reactive
      protein. However, the reaction differed from that of cytokeratins 8 and 18 by
      molecular weight and a pI of 7.5. A significant reactivity to cytokeratin 8 and
      18 preparations was seen in only 1/12 patients. Immunoscreening of a human liver
      expression gene bank yielded no clones with sequence homology to cytokeratins. We
      conclude that reactivity in SLA positive sera is not mainly directed against
      cytokeratins 8/18 and recommend native antigen preparations for diagnostic use
      until the exact molecular nature of the 52 kD SLA antigen has been elucidated.

PMID- 10934581
TI  - Geographic grouping of Cryptococcus neoformans var. gattii by random amplified
      polymorphic DNA fingerprint patterns and ITS sequence divergence.
AB  - Eleven reference strains of Cryptococcus neoformans var. gattii were analyzed by
      random amplified polymorphic DNA (RAPD) patterns using three oligo primers. Three
      major RAPD pattern profiles (profiles I, II and III) were identified with A-1
      oligo primer. Each profile was found to relate to a geographic region. Since the
      strains which belong to profiles I and II were mainly the isolates from America,
      and profile III from Asia with A-1 primer, these three profiles were assigned to
      the geographic grouping of America-1, America-2 and Asia, respectively. Analysis
      of rDNA sequences coding an internal transcribed spacer (ITS) region of C.
      neformans var. gattii revealed that the fungus with each RAPD profile has
      characteristic base sequences at the four positions (10 and 15 positions in ITS1
      and 8 and 56 positions at ITS2) of the ITS regions. On the basis of the
      combinations of the four bases specific for the ITS regions, four ITS types, AAGG
      (America-1), AAAC (America-2), GGGC (Asia-1) and AGGC (Asia-2) were identified:
      the geographic group of Asia was further classified into two subgroups of Asia-1
      and Asia-2 based on the ITS typing. Clinical isolates from Thailand (6 strains)
      and Brazil (7 strains) were found to belong to the geographic group of America-1
      nd America-2, respectively. Five reference strains of C. neoformans var. gattii
      from the CBS culture collection were classified into two America-2, one Asia-1
      and two Asia-2 groups. This ITS region analysis allowed us to distinguish all
      isolates of C. neoformans var. gattii into four geographic groups based on the
      ITS base sequence, and further molecular epidemiological and ecological research
      on this fungus is recommended.

PMID- 10934582
TI  - Evaluation of two commercial procedures for quantification of human
      immunodeficiency virus type 1 RNA with respect to HIV-1 viral subtype and
      antiviral treatment.
AB  - To determine the reliability of two commercial assays for quantifying the human
      immunodeficiency type 1 (HIV-1) RNA levels in patients infected with different
      HIV-1 subtypes and managed with various drug regimens, blind testing of 127
      plasma samples from 57 patients infected with HIV-1 subtypes A, B, C and E was
      performed using the Amplicor HIV-1 Monitor Test (Roche) and Quantiplex HIV-1 RNA
      3.0 Assay (Chiron). Included were time course studies in 7 patients in whom the
      virus load was correlated with CD4+ cell counts and therapy. Both assays were
      accurate and precise to measure standardized amounts of viral load and displayed
      high correlation coefficients that were independent of gender and treatment
      modality, even though some assay-specific differences may exist in the
      quantification of viral subtype RNA. Time course studies showed comparable
      inverse associations between the CD4+ count and viral load measured by the two
      assays. Hence, both the Amplicor HIV-1 Monitor Test and the Quantiplex HIV-1 RNA
      3.0 Assay promise to be useful for the management of HIV-1 infected patients.

PMID- 10934583
TI  - Serum antibodies in celiac disease.
AB  - Celiac disease is characterized by small intestinal damage which often leads to
      global malabsorption. For diagnosis an intestinal biopsy to demonstrate the
      mucosal changes is mandatory. However, serological tests are useful additional
      tools to confirm the diagnosis and to monitor therapy. These serological tests,
      which are based on the detection of antibodies against gliadin and autoantibodies
      against components of the extracellular matrix, are described in this article.

PMID- 10934584
TI  - Cryo-press, a type of sample preparation method based on freeze-fracture.

PMID- 10934586
TI  - [Effect of the novel aminoadamantane derivative A-7 on Parkinsonian syndrome
      induced by systemic administration of neurotoxin MPTP].
AB  - A new antiparkinsonian drug, N-(2-adamantyl)hexamethyleneimine hydrochloride (A
      7), was studied on the model of parkinsonism syndrome (PS) induced by MPTP
      neurotoxin. A-7 (5-20 mg/kg) attenuated the MPTP induced akinesia and rigidity
      manifestations in C57B1/6 mice, the effect being more pronounced than that of
      cyclodol and levodopa and comparable to that of midantane (amantadine). A-7 also
      decreased the PS manifestations in rats: removed tremor, rigidity, and
      oligokinesia, normalized the MPTP-violated bioelectrical activity of nucleus
      caudatus, sensomotor cortex, and dorsal hippocamp, and eliminated pathologic slow
      activity, paroxysmal discharges, and high-frequency activity discharges. The
      activity of A-7 exceeded that of levodopa (enhancing tremor) and cyclodol (not
      eliminating the pathologic slow activity).

PMID- 10934587
TI  - [Participation of D1 dopamine and alpha2 adrenoreceptors in formation of the
      frequency spectrum of the cortical activity in rats].
AB  - Intracerebroventricular injections of the alpha 2-adrenoreceptor agonist
      clonidine (1, 10, and 100 nmole) produced a dose-dependent decrease in the low
      frequency (1.5-3.0 Hz) EEG components and increase in the EEG theta-rhythm (4.3
      7.2 Hz) in freely moving rats with chronically implanted electrodes in the cortex
      and a cannule in the lateral ventricle. The beta-frequency EEG components (20.8
      26.5 Hz) were stimulated by smaller doses of clonidine and reliably inhibited by
      the maximum doses. The alpha 2-adrenoreceptor antagonist yohimbine potentiated
      the effect of clonidine in the theta- and beta-ranges. The D1-dopaminergic
      receptor agonist SKF-38393 (100 nmole) reduced EEG intensity in the 1.9-2.5 and
      9.3-13.8 Hz and increased intensity in the 4.9-5.7 and 20.3-26.5 Hz regions.
      Preliminary injection of the D1-antagonist SCH-23390 prevented from the agonist
      effects in the high-frequency part of the spectrum. The possible participation of
      the pre- and post-synaptic dopaminergic D1- and alpha 2-adrenergic receptors in
      the EEG profile variation under the action of the above agents is discussed.

PMID- 10934588
TI  - [Effects of bromantane and sidnocarb on long-term operant conditioning and its
      vegetative correlates in rats].
AB  - Bromantan (20 mg/kg, p.o.) and sydnocarb (10 mg/kg, p.o.) augment the efficacy of
      a 5-h operant activity in rats, the effect being achieved through different
      pathways. Sydnocarb increases the number of operant reactions and exhausts the
      sympathico adrenal system reserves. Bromantan favors the activity optimization by
      reducing the number of errors at a smaller number of operant reactions. Bromantan
      increases the tension of motivational component (electric pain irritation
      avoidance), whereas sydnocarb decreases this component of the operant behavior.
      None of the two drugs affects the degree of functional activation of the
      cardiovascular system.

PMID- 10934589
TI  - [Bis-ammonium adamantane derivatives--novel modulators of polyamine binding
      sites].
AB  - Experiments on intact rats and mice showed that the polyamine agonist spermine
      and the bis-ammonium adamantyl-containing compounds IEM-1460 and IEM-1754
      potentiate the NMDA induced analgesia and convulsions and eliminate the analgesic
      effects of nicotine and kainate. Arcain, a competitive polyamine antagonist,
      eliminated (at the same dose) the activating and blocking effects of spermine,
      IEM-1460 and IEM-1754. In small doses, IEM-1754 (similarly to arcain) removed the
      analgesic effect of NMDA. It is suggested that IEM-1460 (similarly to spermine)
      is a polyamine agonist, while IEM-1754 is an antagonist/agonist of the polyamine
      site of NMDA, AMPA/kainate, and nicotinic receptors. The potentiating activity of
      IEM-1460 is two orders higher as compared to that of spermine.

PMID- 10934590
TI  - [Tropoxin and cerebrovascular effects of serotonin].
AB  - The effect of serotonin on the brain blood supply was studied in rats before and
      after ischemic damage. The ischemic damage, induced by ligation of the middle
      meningeal artery, markedly enhanced the constrictor effect of serotonin on the
      brain vessels. Tropoxin, a 5HT2 receptor blocker, completely eliminated these
      cerebrovascular effects of serotonin.

PMID- 10934591
TI  - [Comparative analysis of the cardioprotective effect of antioxidant dibunol and
      agonists of mu- and delta-opioid receptors during oxidative stress].
AB  - Upon intravenous injection of the delta-opioid receptor agonists, the isolated
      perfused rat heart became resistant to free radical damage. The cardioprotector
      activity of the delta-receptor agonists is more pronounced than that of the
      antioxidant dibunol. Both dibunol and the delta-receptor agonists favored a
      decrease in the level of diene conjugates in myocardium. Stimulation of the mu
      opioid receptors did not change the resistance of rat heart to the oxidative
      stress.

PMID- 10934592
TI  - [Pharmacodynamics and pharmacokinetics of the new specific bradycardic
      preparation bradizole].
AB  - The new drug Bradizol (SM-345), a 2-mercaptobenzimidazole derivative producing a
      specific bradycardic effect, is quite rapidly eliminated upon intravenous bolus
      in anaesthetiezed cats. After a combined injection (bolus followed by a 60-min
      infusion), a constant bradizol concentration in the blood plasma is observed over
      a time period of 90 min. The bradizol-induced bradycardic effect and the drug
      concentration in the blood plasma are tightly correlated. Upon per os
      administration of bradizol to the experimental animals, neither the drug is
      detected in the blood plasma, nor the bradycardic effect is observed. It is
      suggested that bradizol, possessing antiarrhythmic, antifibrillator, and
      antiischemic properties, can be used (by intravenous injections) for the therapy
      of patients with diverse tachyarrhythmia geneses, including those with the
      ischemic heart disease.

PMID- 10934593
TI  - [Effects of SH-compounds on changes in the antioxidant enzyme activity in various
      tissues during acute pancreatitis].
AB  - In rats with experimental acute pancreatitis, activity of the antioxidant defense
      enzyme in pancreatic and liver tissues increases, while that in the blood
      erythrocytes decreases. Preliminary administration of SH-compounds, especially
      unithiol, favored an increase in the activity of superoxide dismutase, catalase,
      and glutathione peroxidaze.

PMID- 10934594
TI  - [Effect of the long term administration of bromantan on the reproductive function
      in rats].
AB  - Bromantan is a new psychostimulator possessing actoprotector properties. The drug
      was administered to rats over two months (males) and two weeks (females) at a
      daily dose of 30 and 200-mg/kg, and the reproduction function parameters were
      monitored. Then the experimental animals were coupled and the embryonal
      characteristics of the breed were determined. Upon termination of the drug
      administration, the functional state of sperm and the morphology of gonads were
      studied again. It was found that bromantan (30 mg/kg) unreliably decreases the
      absolute amount of sperm in males. In females, the drug did not affect the ovary
      weight coefficient and increased the gestation index. After termination of the
      drug administration, the ovary weight coefficient increased. Bromantan affected
      neither the fertilizing capacity of male and female gametes nor the embryonal
      characteristics of the breed.

PMID- 10934595
TI  - [Antithrombotic activity of para-aminobenzoic acid].
AB  - Mechanisms of the anticoagulant activity of p-aminobenzoic acid (PABA) were
      studied. The specific antithrombin activity of PABA is aIIa = 7.00 +/- 0.32 IU/mg
      and the specific antiactivated factor Xa activity is aXa = 6.70 +/- 0.12 IU/mg.
      Study of the antithrombotic activity of PABA in rats with a model of venous
      stasis showed that intravenous injection of PABA at a dose of 1.5 mg/kg prevented
      the experimental thrombosis development 1.5 h after injection. The activity
      exhibited a peak 3 h after drug injection and ceased by the 5th hour. Equal
      antithrombotic activity in the rat blood plasma was observed for fraxiparin at a
      dose of 40 aXa IU/kg and PABA at 25 aXa IE/kg (1.5 mg/kg). At the same time, PABA
      affected neither the number of thrombocytes nor their response to the thrombocyte
      aggregation factors (ADP or adrenaline).

PMID- 10934596
TI  - [Inhibitory effects of serotonin and sodium ascorbate on the oxidative
      aggregation of lipoproteins].
AB  - Milk lipoproteins (MLPs) are structurally and biochemically similar to blood
      lipoproteins, which allow the former to be used as model objects for studying the
      properties of the latter. The results of turbidimetric measurements showed a
      change in the light scattering from MLP suspensions upon contact with Fe3+ ions
      in the free from or in chelate complexes with o-phenanthroline and EDTA. No such
      effect was observed for Fe2+ ions. The effect of Cu2+ ions (in microscopic
      amounts) was similar to that of Fe3+, while Ca2+ and Mg2+ produce no effect. It
      was found that 1,1-azabicyclohexanecarbonitrile-2-methylpropionamidine
      dihydrochloride (an azoinitiator capable of spontaneous decomposition with the
      formation of peroxide radicals in an oxygen containing-medium) introduced into an
      MLP suspension produces the same effect as Fe3+ and Cu2+ ions. Study of the
      particle size distribution in a microcapillary by the method of impedance
      measurements showed that a change in the light scattering from the suspension is
      caused by the MLP aggregation. The action of aggregation factors upon the MLPs
      led to their oxidation, as indicated by accumulation of the TBA-active products.
      The ability of copper ions to oxidize MLPs agrees with the data reported on the
      copper-ion-induced oxidation of blood lipoproteins, which was observed in
      studying a relationship between this oxidation and clinical manifestations of
      atherosclerosis. Thus, pronounced oxidation of both milk an blood lipoproteins in
      the presence of microscopic amounts of copper ions is indicative of a similarity
      of these processes. The process of lipoprotein aggregation induced by various
      oxidizing agents is inhibited by sodium ascorbate and serotonin. At the same
      time, beta-naphthol (an antioxidant soluble in lipids) does not affect the
      aggregation process. It is suggested that the oxidative aggregation of
      lipoproteins mag be related to the problem of atherogenesis and thrombogenesis.

PMID- 10934598
TI  - [Pharmacological study of papain from the papaya plant cultivated in Uzbekistan].
AB  - It was experimentally established that papain from papaya cultivated in
      Uzbekistan possesses a pronounced proteolytic activity: 0.1, 0.5, and 1% papain
      solutions decreased the weight of burn crust in vitro and accelerated
      experimental burn healing in vivo. Under clinical conditions, papain produced
      therapeutic effect in patients with inflammatory disorders in genitals,
      intestine, liver, and eye. The pharmacological effects of papain produced from
      Uzbek papaya are identical to those of the commercial product from Merck.

PMID- 10934597
TI  - [Alcohol consumption and anti-alcohol effect of afobazol in MR and NMRA rats].
AB  - Dynamics of the alcohol intake variation in MR and MNRA inbred rats with
      different emotional-stress reaction (ESR) phenotypes was studied in the course of
      a 7-month voluntary alcoholization. Initially, the MNRA rats with an active ESR
      phenotype showed a higher level of a 15% aqueous ethanol consumption than did the
      MR rats. After 3 months, the consumption of ethanol in the highly emotional MR
      rats sharply increased and was retained on a high level during subsequent
      alcoholization. The new anxiolytic agent afobazol [5-ethoxy
      2(morpholinoethylthio)-benzimidazole hydrochliride] did not potentiate the CNS
      depressant action of alcohol. A 2-week administration of afobazol (1 mg/kg, i.p.)
      after a 6-month alcoholization markedly reduced the alcohol consumption and
      reduced the craving to alcohol in the rats of both lines studied.

PMID- 10934599
TI  - [Anxiety models on mice: experimental evaluation and criticism of the method].
AB  - The analysis of publications in the field of experimental psychopharmacology (in
      particular, anxiety models) shows a lack of data concerning the general
      methodological problems such as reproducibility and reliability of data. There
      are only a few works where important characteristics concerning solution pH, sham
      injections, body temperature, locomotion indices (basal and injection-modulated),
      etc, are reported. Figures on the illumination level in experimental chambers are
      generally missing. Three simplest, fastest, and most commonly used anxiety models
      (dark-light compartments, social isolation test, elevated plus-maze) are
      considered with special attention to the mistakes and artifacts most frequently
      encountered in registration of the experimental animal behavior and in the data
      interpretation.

PMID- 10934600
TI  - [Brain ischemia induced by gravitational overload].
AB  - It is suggested that radial gravitational overloads in craniocaudal direction,
      during which the pressure in meningeal arteries drops to zero, can be used to
      model the ischemic state. The post-ischemic period is characterized by increasing
      content of lipid peroxidation products in the venous blood and by violation of
      the neurological state in rats. This ischemia model, requiring no anaesthesia for
      the experimental animals, can be used in the directed search for new
      neuroprotectors and their characterization.

PMID- 10934601
TI  - [Efficacy of purine nucleotides on purinergic P2 platelet receptors by small
      angle light scattering].
AB  - The effect of purines on the activation and aggregation of thrombocytes in rats
      and rabbits was studied by the method of small-angle light scattering. The EC50
      values of ADP, inducing the activation and aggregation of thrombocytes, reflect
      the sequence of the agonist action on various receptors: P2X1, 20-40 nM; P2Y1, 90
      110 nM; P2YADP, 120-240 nM. It was demonstrated that ADP behaves as partial
      agonist not only with respect to P2X1 receptors, but with respect to P2Y1
      receptors as well. Thrombocytes activated by 20 nM ADP or 100-nM ATP pass into a
      refracter state in the absence of further stimulation. The reaction halftime is
      tau 1/2 = 6.0 +/- 0.2 min for the cells activated with ADP and tau 1/2 = 16.5 +/-
      0.2 min for ADP.

PMID- 10934602
TI  - [Acamprosate--a novel treatment for alcoholism].
AB  - The properties of acamprosate (calcium acetylhomotaurate), a new remedy for the
      treatment of alcoholism, are reviewed. The efficacy of this drug has been
      verified by numerous clinical tests in West Europe. The pharmacological activity
      of acamprosate is related to the drug action upon central neuromediator systems.
      No side or addiction effects of the drug were reported. Data on the clinical and
      pharmacological characteristics of acamprosate are summarized.

PMID- 10934603
TI  - [Bisphosphonates in pharmacotherapy of bone diseases].
AB  - Bisphosphonates represent a new class of drugs that has been developed in the
      past three decades for the treatment of various bone diseases and calcium
      metabolism disorders. Possessing high affinity to the bone-forming minerals,
      these substances can be used as inhibitors of the ectopic calcification and bone
      resorption. Bisphosphonates not only prevent from the loss of bones in the case
      of osteoporosis of various types (e.g., after the menopause), but provide for an
      increase in the bone mineral density as well. Therefore, these drugs offer an
      important additional means of therapy in cases of osteoporosis and other bone
      disorders.

PMID- 10934604
TI  - [An investigation of factors associated with failure of extracorporeal shock wave
      lithotripsy for ureteral calculi].
AB  - In this study, we attempted to determine which patients with ureteral calculi are
      likely to have an unsuccessful outcome for extracorporeal shock wave lithotripsy
      (ESWL). The records of 388 patients with ureteral calculi treated with ESWL at
      Ijinkai Takeda General Hospital between January 1997 and December 1998 were
      retrospectively reviewed. Three hundred seventeen patients had been treated with
      ESWL alone (single session 156, multiple sessions 161) and 71 with transurethral
      ureterolithotripsy (TUL) due to failure of ESWL. We compared these two groups by
      multivariate logistic regression analysis, which revealed that (1) middle and
      lower ureteral calculi, (2) stones > 8 mm, (3) moderate to severe hydronephrosis
      and (4) failure of the first session ESWL were factors associated with poor
      outcome of ESWL. Although each predictive value of these factors was relatively
      low (29.6-38.6%), the rate of failure of ESWL was 85.0% when patients had all
      four factors. We therefore recommend an early change in treatment modality to TUL
      for patients with ureteral calculi when all four risk factors listed above are
      present.

PMID- 10934605
TI  - [The relationships among DNA ploidy type determined by laser scanning cytometry,
      the overexpression of p53 protein and the numerical aberrations of chromosome 7
      in bladder cancer].
AB  - The cellular DNA content of certain malignancies is regarded as a prognostic
      parameter. The mutant p53 is thought to destabilize centrosome replication, which
      leads to aberrant mitosis and chromosome instability. We investigated the
      relationship among DNA ploidy pattern type, numerical aberrations of chromosome 7
      and p53 overexpression in 20 transitional cell carcinomas of the urinary bladder.
      The DNA ploidy pattern type was determined by laser scanning cytometry, while p53
      overexpression was investigated immunohistochemically. Using fluorescence in situ
      hybridization with chromosome-specific probes, the copy number of chromosome 7
      was counted by touch preparations of interphase nuclei. The cytometric analysis
      revealed that the DNA patterns were highly correlated with both the numerical
      aberrations of chromosome 7 (p = 0.0002) and the overexpression of p53. The
      incidences of p53 overexpression in DNA aneuploid tumors and DNA diploid ones
      were 78% and 10%, respectively (p = 0.0017). Our results suggest that the
      overexpression of abnormal p53 protein induces DNA aneuploidy in bladder cancer.

PMID- 10934606
TI  - [Clinical features of multiple primary cancers including prostate cancer].
AB  - We analyzed the clinical features of multiple primary cancers (MPCs) that
      included prostate cancer. MPCs were observed in 93 (15.2%) of the patients
      suffering from prostate cancer. In the MPC group, the organ most commonly
      involved was the stomach, followed by bladder, colon and lungs. The median age at
      diagnosis of the first, second and third cancers was 72, 74, and 75 years old,
      respectively, and the duration between the first and second cancers (median: 20
      months) was longer than that between the second and third cancers (median: 8
      months). In the 37 MPC patients whose cause of death was obvious, 29 (78.4%) died
      of a cancer; prostate cancer was not so common (6 patients) as the cause of
      death. Age at diagnosis and grade distribution of prostate cancer were not
      significantly different between the MPC and single primary cancer (SPC) groups.
      However, the proportion of earlier stage was significantly (p < 0.01) higher in
      the MPC group than in the SPC group, and this trend was more obvious in patients
      whose prostate cancer was diagnosed as the second cancer. The prostate cancer
      specific survival rates were significantly higher in the patients with MPC, and
      this trend was more obvious in the patients with stage D or moderately
      differentiated cancer. It is important in the follow up of prostate cancer
      patients to be aware of the possibility of the occurrence of a second cancer.

PMID- 10934607
TI  - [Retroperitoneal paraganglioma incidentally detected by health examination: a
      case report].
AB  - We report a case of non-functioning retroperitoneal paraganglioma detected
      incidentally by health examination in a 60-year-old female without any clinical
      manifestation. She was admitted to our hospital for the purpose of evaluation of
      a renal mass detected by ultrasound sonography. Computed tomography, magnetic
      resonance imaging and angiography revealed the heterogeneously-enhanced 10 x 10
      cm mass in the left retroperitoneal space without any distant metastasis. It was
      suspected to be a renal cell carcinoma. All laboratory data, including those from
      endocrinological examinations, were within normal ranges. Radical nephrectomy was
      performed to resect en bloc the mass and the left kidney. The pathological and
      immunohistochemical examinations of the mass which was completely separated from
      the kidney and the adrenal gland, showed characteristic features of paraganglioma
      with vascular and capsular invasion, with a final clinical diagnosis of the
      pathologically-malignant non-functioning paraganglioma occurring between the left
      kidney and the adrenal gland.

PMID- 10934608
TI  - [A case of chromophobe cell renal carcinoma].
AB  - We report a case of chromophobe cell renal carcinoma. A 27-year-old male suffered
      from right flank pain and gross hematuria. Drip infusion pyelography and
      ultrasonographic examination revealed a right renal mass and it was diagnosed as
      renal oncocytoma by needle biopsy of the right kidney. He was referred to our
      hospital for the operation and right radical nephrectomy was performed. The cut
      surface of the tumor was beige in color. The cytoplasm of the tumor cells stained
      positively for colloidal iron and showed a negative reaction for Vimentin. From
      these results, this tumor was given a diagnosis of chromophobe cell renal
      carcinoma.

PMID- 10934609
TI  - [Bellini duct carcinoma of the kidney: a case report].
AB  - This is a report of a case of Bellini duct carcinoma of the kidney. A 72-year-old
      male was admitted to our hospital for the treatment of left renal tumor. The
      abdominal computed tomographic scan showed hypoattenuating tumor with
      infiltrative spread into the renal cortex. The renal angiography revealed a
      hypovascular tumor. Left nephro-ureterectomy was performed because transitional
      cell carcinoma was suspected in the frozen section. The gross examination
      revealed an infiltrating white-gray tumor centered in the renal medulla. No
      hemorrhage was discovered, but partial necrosis was found. Capsular infiltration
      was not seen. Histologically, tumor cells were mostly scattered and partially
      showed a papillary and tubular structure. Cells had abundant eosinophilic
      cytoplasm and large irregular nuclei. Immunohistochemical studies revealed
      positive reactions for cytokeratin, epithelial membrane antigen and ulex
      europaeus agglutinin. We diagnosed this patient with Bellini duct carcinoma. He
      died due to drastic progression of metastasis from carcinoma two months
      postoperatively.

PMID- 10934610
TI  - [Adult Wilms' tumor: a case report].
AB  - We present a case report of adult Wilms' tumor and reviewed from 1981. A 22-year
      old woman with chief complaints of gross hematuria and right backache was
      introduced to our hospital in March 1998. Abdominal computed tomography (CT)
      revealed a solitary irregular mass (5.0 cm) at the lower pole of right kidney
      with no contrast medium enhancement. Angiography showed a hypovascular character,
      but irregular vascularization was found in the tumor. We performed a radical
      nephrectomy with a preoperative diagnosis of malignant renal tumor. Finally,
      adult Wilms' tumor (epithelial type) was diagnosed by pathological examination.
      We retrospectively studied the clinical and radiological features in 16 reported
      cases of adult Wilms' tumor from 1981. The average age was distinctly younger
      than that of renal cell carcinoma. Nearly half of the cases were at an advanced
      clinical stage (direct invasion or metastasis to other organs) at first
      consultation. Radiologically, Wilms' tumor tends to be visualized as a low
      density mass in the precontrast CT scan (75.0%) and hypovascular tumor by
      selective angiography (84.6%). Although this is not a definitive character to
      distinguish adult Wilms' tumor from renal cell carcinoma, it may be useful
      information for differential diagnosis.

PMID- 10934611
TI  - [Renocolic fistula: a case report].
AB  - A 78-year-old woman had disregarded pneumaturia since April 1998. In March 1999,
      computed tomography and barium enema were done to examine anemia and positive
      fecal occult blood, revealing a left renocolic fistula and bilateral renal
      stones. Intravenous pyelography revealed a left staghorn calculus, non
      functioning kidney, and right partial staghorn calculus. Urinalysis showed pyuria
      and the culture grew Proteus vulgaris and Klebsiella oxytoca. Smear and culture
      of the urine were negative for acid-fast bacilli. In consideration of the
      patient's age and conservation of right renal function, right pyelolithotomy was
      performed first. Three weeks later, left nephrectomy and partial colectomy were
      done. The postoperative course was uneventful. A renocolic fistula is relatively
      rare and to our knowledge there have been 37 cases reported in Japan, including
      our case. Surgery is the main therapy and was performed in 31 patients. Among
      them, surgery was not curative in 1 and 5 died of postoperative complications.
      Thus, surgery is not safe in all cases. However, despite her age and bilateral
      renal dysfunction, our patient was successfully operated on.

PMID- 10934612
TI  - Retroperitoneoscopic heminephrectomy of the right upper collecting system
      emptying into an ectopic ureterocele in a 5-year-old girl: a case report.
AB  - A 5-year-old girl with a history of recurrent urinary tract infection since the
      age of 14 months was diagnosed as having a right duplicated urinary collecting
      system with the upper ureter ectopically opening in the urethra. She underwent
      retroperitoneoscopic heminephrectomy for a right dysplastic kidney and open
      ureterocelectomy and reimplantation of the refluxing lower ureter via
      Pfannenstiel incision. She survived the procedure without serious complications
      and resumed normal daily activities by day 6. To the best of our knowledge, this
      case is the 16th case of laparoscopic heminephrectomy for pediatric patients and
      the first case treated by the retroperitoneal approach in the English literature.

PMID- 10934613
TI  - [A case of patent urachus in an adult male].
AB  - A 31-year-old man was referred to our hospital for evaluation of urachal rest.
      The history of his present illness dated back to birth, when the umbilicus was
      projected and urinary discharge was noted. At that time, the symptom of discharge
      had spontaneously subsided. At the age of 22, however, the patient again
      experienced discharge from the umbilicus. Although he did not seek treatment,
      after six years this symptom disappeared. Around this time, however, pyuria was
      revealed during medical examination, and abdominal ultrasonography (US) suggested
      the presence of urachal rest. At the time of hospitalization, physical
      examination revealed that the patient's right testis was not palpable. He was
      diagnosed with patent urachus with hemilateral aplasia and monorchism by US,
      computed tomography, magnetic resonance imaging and cystoscopy. The patient
      subsequently underwent radical operation. Patent urachus in adults is very rare,
      and only a few cases have been reported. To our knowledge, only one previously
      reported case involved a recurrence after spontaneous healing. Further, this is
      the first report of a patient with patent urachus with hemilateral aplasia and
      monorchism. Radical operation is generally recommended, based on the fact that
      very few cases heal conservatively.

PMID- 10934615
TI  - [A case of prostatic small cell carcinoma].
AB  - A 66-year-old man was referred to our hospital with a complaint of lumbago.
      Digital rectal examination showed an enlarged, irregular prostate with stony
      hardness. The serum level of prostate specific antigen (PSA) was elevated.
      Abdominal computed tomography showed enlarged common iliac and paraaortic lymph
      nodes, and multiple liver metastases. Bone scintigraphy showed multiple bone
      metastases. Histological and immunohistochemical examinations indicated small
      cell carcinoma and adenocarcinoma of the prostate. Chemotherapy could not be
      performed due to acute hepatic failure. The patient died 1 month after his first
      visit.

PMID- 10934614
TI  - [Localized amyloidosis of the ureter and bladder treated effectively by occlusive
      dressing technique therapy using dimethyl sulfoxide: a case report].
AB  - We report here the first case of localized amyloidosis of the ureter and bladder
      to be treated effectively by occlusive dressing technique therapy using dimethyl
      sulfoxide. The patient was a 48-year-old woman whose chief complaint was
      macrohematuria and right back pain. Ultrasound sonography demonstrated right
      hydronephrosis and an intravesical mass in the region of the right ureteral
      orifice. Retrograde pyelography revealed severe stricture of the right lower
      ureter. Cystoscopy demonstrated a yellow submucosal tumor around the right
      ureteral orifice. We suspected urinary tract amyloidosis, and transurethral
      biopsy and resection of the intravesical mass were performed under right ureteral
      stenting. Histopathological diagnosis was amyloidosis. There was no evidence of
      systemic amyloidosis. To treat residual amyloidosis of the ureter and bladder, we
      performed occlusive dressing technique therapy using dimethyl sulfoxide every
      day. After 6 months of therapy, the right hydronephrosis disappeared, and there
      was no evidence of a recurrence of amyloidosis. We concluded that this therapy
      was very effective and safe for urinary tract amyloidosis.

PMID- 10934616
TI  - [Extensive Fournier's gangrene: a case report].
AB  - We report a case of extensive Fournier's gangrene that could not be rescued
      despite emergent debridement. A 51-year-old man presented at another hospital
      with cough, diarrhea and abdominal pain. He was diagnosed with acute enteritis
      and hospitalized. The next morning, he became severely hypotensive and his
      scrotum was swollen and black. The perineal skin also was black. Septic shock and
      disseminated intravascular coagulation were suspected. He was transferred to our
      emergency room, and was immediately diagnosed with Fournier's gangrene and acute
      peritonitis. Computed tomographic scan revealed soft-tissue gas in the scrotum,
      the retroperitoneal cavity and the abdominal wall. Emergent debridement and
      laparotomy was performed. Gangrene was also seen at the intestinal wall and the
      peritoneum, however, resection of intestine was not done because of his poor
      performance status. Although potent antibiotics and catecholamine were
      administered, he died of multiple organ failure 29 hours after the operation.
      This is the first case of Fournier's gangrene extending into the abdominal cavity
      reported in the Japanese literature.

PMID- 10934617
TI  - [Labial adhesion in a reproductive woman with difficulties of sexual intercourse
      and urination: a case report].
AB  - A 27-year-old female patient consulted us with chief complaints of difficulties
      of sexual intercourse and urination. On examination, the labia was found to be
      extensively fused at the midline, with a pinhole opening. We diagnosed it as
      labial adhesion. We operated on it under lumbar anesthesia. Four months after the
      operation, there were no symptoms of recurrence. Labial adhesion is thought to be
      caused by inflammation, lack of sexual activity and estrogen deficiency. It is
      not uncommon in children and post-menopausal women, but is extremely rare in
      reproductive women.

PMID- 10934618
TI  - Damage control mechanisms in articular cartilage: the role of the insulin-like
      growth factor I axis.
AB  - Articular chondrocytes maintain cartilage throughout life by replacing lost or
      damaged matrix with freshly synthesized material. Synthesis activity is
      regulated, rapidly increasing to well above basal levels in response to cartilage
      injury. Such responses suggest that synthesis activity is linked to the rate of
      matrix loss by endogenous "damage control" mechanisms. As a major stimulator of
      matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to
      play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its
      bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs)
      secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I
      axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block
      IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently
      found that the expression of one binding protein, IGFBP-3, increases with
      chondrocyte age, paralleling an age-related decline in synthesis activity. In
      addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to
      metabolic disturbances that contribute to cartilage degeneration. These
      observations indicate that IGFBP-3 plays a crucial role in regulating matrix
      synthesis in cartilage, and suggest that cartilage damage control mechanisms may
      fail due to age-related changes in IGFBP-3 expression or distribution. Our
      investigation of this hypothesis began with immunolocalization studies to
      determine the tissue distribution of IGFBP-3 in human cartilage. We found that
      IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix,
      where it co-localized with fibronectin, but not with the other matrix proteins
      tenascin-C and type VI collagen. This result suggested that the IGFBP-3
      distribution is determined by binding to fibronectin. Binding studies using
      purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but
      not to tenascin-C or type VI collagen. Finally, we investigated the metabolic
      effects of fibronectin and IGFBP-3 in a chondrocyte culture system. These
      experiments showed that fibronectin enhanced the inhibitory effect that low
      concentrations of IGFBP-3 had on matrix synthesis. Taken together, these
      observations confirm that IGFBP-3-fibronectin interactions affect the IGF-I axis,
      and they indicate that IGF-I is stored in the chondrocyte territorial matrix
      through binding to a complex of IGFBP-3 and intact fibronectin. This arrangement
      may play an important role in cartilage damage control mechanisms. The local
      increase in matrix synthesis following injury could result from damage-induced
      IGF-I release from such pools. An age-related failure to organize this system may
      contribute to degenerative disease.

PMID- 10934619
TI  - Transforming growth factor beta one (TGF-beta 1) enhancement of the chondrocytic
      phenotype in aged perichondrial cells: an in vitro study.
AB  - BACKGROUND: Perichondrium is recognized as a tissue with chondrogenic potential
      yielding cells which can be used for osteochondral repair. Factors which
      influence the proliferative ability and chondrocytic phenotype of such cells
      include age and presence of specific growth factors, i.e. TGF-beta 1. The present
      in vitro study assessed proliferation and markers of chondrocytic phenotype in
      cells extracted from the rib perichondrium of four- to five-year-old aged
      rabbits, and assessed the effects of exogenously added TGF-beta 1 on those cells.
      METHODS: Assays included 3H-thymidine incorporation (cell proliferation), 35S
      sulfate incorporation (proteoglycan synthesis) and quantitative RT-PCR for
      determination of type II collagen gene expression. RESULTS: The results
      demonstrated that addition of TGF-beta 1 to the culture media stimulated
      thymidine incorporation and proteoglycan synthesis up to four- and five-fold,
      respectively, in aged perichondrium-derived cells. Moreover, the exogenous
      addition of TGF-beta 1 to the culture media resulted in an upregulation of
      transcriptional expression of the type II collagen gene. CONCLUSIONS: In summary,
      the present study has demonstrated that exogenously added TGF-beta 1 can
      stimulate proliferation and chondrocytic phenotype in aged perichondrium-derived
      cells in vitro.

PMID- 10934620
TI  - Open reduction and cementation for femoral head fracture secondary to avascular
      necrosis: preliminary report.
AB  - Current treatment for femoral head avascular necrosis has shown good results in
      early stages of disease, but are not as impressive after progression to collapse.
      We treated 19 patients (20 hips) with Stage III avascular necrosis (AVN) by open
      reduction augmented by methylmethacrylate cementation. Follow up ranges from 6
      months to 2 years (average = 8.7 months). We followed patient progress with pre-
      and post-operative Harris Hip Scores, Womac Osteoarthritis Index and a Health
      Status Questionnaire (SF36). All patients realized immediate post-operative pain
      relief and improvement in function. Harris Hip, Womac Osteoarthritis Index and
      SF36 physical health scores improved significantly from 54.0 to 79.5 (p < 0.05),
      54.3 to 29.8 (p < 0.05) and 28.4 to 42.4 (p < 0.05), respectively. Three patients
      had a conversion to total hip arthroplasty. Cementation is technically simple,
      burns no bridges and enables patients a rapid recovery. The long term results, in
      regards to progression of disease and secondary arthritis, are unknown.

PMID- 10934621
TI  - High density polyetherurethane foam as a fragmentation and radiographic surrogate
      for cortical bone.
AB  - BACKGROUND: Although one of the most important factors in predicting outcome of
      articular fracture, the comminution of the fracture is only subjectively
      assessed. To facilitate development of objective, quantitative measures of
      comminution phenomena, there is need for a bone fragmentation surrogate. METHODS:
      Laboratory investigation was undertaken to develop and characterize a novel
      synthetic material capable of emulating the fragmentation and radiographic
      behavior of human cortical bone. RESULT: Screening tests performed with a drop
      tower apparatus identified high-density polyetherurethane foam as having suitable
      fragmentation properties. The material's impact behavior and its quasi-static
      mechanical properties are here described. Dispersal of barium sulfate (BaSO4) in
      the resin achieved radio-density closely resembling that of bone, without
      detectably altering mechanical behavior. The surrogate material's ultimate
      strength, elastic modulus, and quasi-static toughness are within an order of
      magnitude of those of mammalian cortical bone. The spectrum of comminution
      patterns produced by this material when impacted with varying amounts of energy
      is very comparable to the spectrum of bone fragment comminution seen clinically.
      CONCLUSIONS: A novel high-density polyetherurethane foam, when subjected to
      impact loading, sustains comminuted fracture in a manner strikingly similar to
      cortical bone. Moreover, since the material also can be doped with radio
      opacifier so as to closely emulate bone's radiographic signature, it opens many
      new possibilities for CT-based systematic study of comminution phenomena.

PMID- 10934622
TI  - Antibiotic bead production.
AB  - We are reporting a practical technique for the production of antibiotic beads for
      use in combating musculoskeletal infections. The technique utilizes bead molds
      with tobramycin powder mixed with polymethylmethacrylate on twisted wire strands
      to produce strands of 25 beads of various sizes. These beads are gas sterilized
      and available for use "off the shelf" in a manner that is much more efficient
      than traditional production by hand on the back table in the operating room. Our
      technique was also utilized at a second institution to demonstrate its efficacy
      at another site.

PMID- 10934624
TI  - Differences in men's and women's mean ankle ligamentous laxity.
AB  - The incidence of ligamentous ankle injuries is known to be one of the most common
      athletic injuries that exists. Recently, there has been a great deal of interest
      regarding the increased risk of female ligamentous injury, such as the anterior
      cruciate ligament, lateral ankle sprains and others. The purpose of this study is
      to evaluate whether or not normal lateral ankle ligamentous laxity is similar in
      male and female athletes. This study selects 22 male and 27 female college
      athletes who have had no significant ligamentous ankle injuries requiring medical
      treatment. They were placed on a Telos ligamentous stress device and stressed to
      a level of 15 daN. Radiographs were then obtained to determine talar tilt at this
      level of ankle stress. Results were compared between men and women showing that
      there was a statistically significant difference. Women had a much greater
      ligamentous laxity of the lateral ankle than men.

PMID- 10934623
TI  - Blood management and patient specific transfusion options in total joint
      replacement surgery.
AB  - Strategies for blood management in the perioperative period of total joint
      replacement are changing with the better understanding of blood loss and blood
      replacement options in this population. The preoperative, intraoperative and
      postoperative options for blood management are outlined. Rationale for patient
      specific options are described.

PMID- 10934626
TI  - Treatment of idiopathic clubfoot: an historical review.
AB  - Idiopathic clubfoot, one of the most common problems in pediatric orthopaedics,
      is characterized by a complex three-dimensional deformity of the foot. The
      treatment of clubfoot is controversial and continues to be one of the biggest
      challenges in pediatric orthopaedics. This controversy is due in part to the
      difficulty in measuring and evaluating the effectiveness of different treatment
      methods. We believe the heart of the debate is a lack of understanding of the
      functional anatomy of the deformity, the biological response of young connective
      tissue to injury and repair, and their combined effect on the long-term treatment
      outcomes. The aim of this review is not only to assess the different methods of
      clubfoot treatment used over the years in light of an evolving understanding of
      the pathoanatomy of the deformity, but to also clarify factors that allow a safe,
      logical approach to clubfoot management. Further research will be needed to fully
      understand the pathogenesis of clubfoot, as well as the long-term results and
      quality of life for the treated foot.

PMID- 10934625
TI  - Is bone a target-tissue for the nervous system? New advances on the understanding
      of their interactions.
AB  - Bone cells respond in specific ways to various hormones and growth factors, but
      the biology of skeletal innervation and its physiologic significance in bone
      metabolism is poorly understood. With the introduction of immunohistochemical
      staining techniques and new molecular biology tools, the knowledge in this field
      has significantly improved. In this review, we update current understanding of
      the effects of neuropeptides on bone metabolism, specifically vasoactive
      intestinal peptide (VIP) and calcitonin-gene related peptide (CGRP). In addition,
      new information concerning the role of growth factors, such as neurotrophins, is
      also discussed. There is strong evidence to suggest that bone can be a target of
      the nervous system. Further investigations in this field will allow us to answer
      questions related to pre-natal development, bone growth, fracture healing,
      osteoporosis, osteoarthritis or neoplasias of mesoderm origin.

PMID- 10934627
TI  - Diabetic muscle infarction.
AB  - Diabetic muscle infarction is a rare complication of diabetes mellitus that is
      not clearly defined in the orthopaedic literature. This study is a descriptive
      case series of 7 new cases of diabetic muscle infarction and 55 previously
      reported cases in the literature. In the majority of patients, diabetic muscle
      infarction presents as a localized, exquisitely painful swelling and limited
      range of motion of the lower extremity. No cases affecting the muscles of the
      upper extremity have been observed. The onset is usually acute, persists for
      several weeks, and resolves spontaneously over several weeks to months without
      the need for intervention. Diabetic muscle infarction is a condition that should
      be considered in the differential diagnosis of any diabetic patient with lower
      extremity pain and swelling without systemic signs of infection. Magnetic
      resonance imaging is sensitive and specific enough to make the diagnosis. Muscle
      biopsy and surgical irrigation and debridement are not recommended since they are
      associated with complications. Pain management and activity restriction in the
      acute phase followed by gentle physical therapy is the treatment of choice.
      Recurrences in the same or opposite limb are common. Although the short-term
      prognosis is very good and the majority of cases resolve spontaneously, the long
      term survival is uncertain in this patient population.

PMID- 10934628
TI  - Volar plate arthroplasty of the thumb interphalangeal joint.
AB  - The fibrocartilaginous volar plate of the thumb interphalangeal joint is
      anatomically quite similar to the volar plate of the digital proximal
      interphalangeal joint. Due to this similarity, Eaton's technique of volar plate
      arthroplasty may also be utilized in fracture-dislocations of the thumb
      interphalangeal joint.

PMID- 10934630
TI  - The future of orthopaedic basic and clinical research: where have we been? Where
      should we go? How do we get there?

PMID- 10934629
TI  - Stress fracture of the hip and pubic rami after fusion to the sacrum in an adult
      with scoliosis: a case report.
AB  - Correction of adult scoliosis frequently involves long segmental fusions, but
      controversy still exists whether these fusions should include the sacrum. It has
      been suggested that forces associated with activities of daily living transfer
      the stresses to the remaining levels of the spine and to the pelvis. The case
      described here was a 43-year-old woman with scoliosis and chronic back pain
      refractory to non-surgical modalities. Radiographically, the patient had a 110
      degree lumbar curve. An anterior and posterior fusion with Luque-Galveston
      instrumentation was performed. Six months postoperatively the patient returned
      with a 2-week history of right hip pain with no history of trauma. There was
      radiographic evidence of a displaced femoral neck fracture and pubic rami
      fractures. The femoral neck fracture was treated with a total hip replacement.
      Further surgeries were required to correct a lumbar pseudoarthrosis and hardware
      failure. We believe that this case provides evidence that fusion into the
      lumbosacral junction may distribute forces through the pelvic bones and hip
      resulting in stress and potential hardware complications, especially in patients
      at risk due to osteopenic conditions.

PMID- 10934631
TI  - Academic medicine and industry--the ethical dilemma.

PMID- 10934632
TI  - Back to the future?

PMID- 10934633
TI  - The misinformation boom.

PMID- 10934634
TI  - Orthopaedic professional scientific organizations what should their role be? How
      should they be managed?

PMID- 10934635
TI  - Using root cause analysis to address patient satisfaction and other improvement
      opportunities.
AB  - BACKGROUND: Despite the considerable attention that health care organizations are
      devoting to the measurement of patient satisfaction, there is often confusion
      about how to systematically use these data to improve an organization's
      performance. A model to use in applying traditional quality improvement methods
      and tools to patient satisfaction problems includes five primary steps: (1)
      identifying opportunities, (2) prioritizing opportunities, (3) conducting root
      cause analysis, (4) designing and testing potential solutions, and (5)
      implementing the proposed solution. PATIENT SATISFACTION SURVEYS: A satisfaction
      survey serves best as a high-level screening device, not as a tool to provide
      highly detailed information about the root causes of patient dissatisfaction. The
      primary purpose of the survey in the model is to identify improvement
      opportunities and areas of significant improvement or deterioration. Secondary
      tools such as brief patient interviews or focus groups may better serve to probe
      intensively into the problem areas identified by the survey. These tools allow
      for a direct dialog with the patient to uncover root causes of dissatisfaction
      and establish potential solutions. DISCUSSION: Although the primary focus of this
      model has been patient satisfaction issues, the basic steps could easily be
      applied to virtually any improvement opportunity. Improvement teams should commit
      to a schedule of 90-minute weekly meetings for 7 weeks. The model, a simple
      translation of traditional improvement methods and tools to address the unique
      issues facing patient satisfaction improvement teams, can save improvement teams
      considerable time, resources, and frustration as they design and launch
      initiatives to improve patient satisfaction.

PMID- 10934636
TI  - Internet-based monitoring and benchmarking in ambulatory surgery centers.
AB  - BACKGROUND: Each year the number of surgical procedures performed on an
      outpatient basis increases, yet relatively little is known about assessing and
      improving quality of care in ambulatory surgery. Conventional methods for
      evaluating outcomes, which are based on assessment of inpatient services, are
      inadequate in the rapidly changing, geographically dispersed field of ambulatory
      surgery. Internet-based systems for improving outcomes and establishing
      benchmarks may be feasible and timely. METHODS: Eleven freestanding ambulatory
      surgery centers (ASCs) reported process and outcome data for 3,966 outpatient
      surgical procedures to an outcomes monitoring system (OMS), during a
      demonstration period from April 1997 to April 1999. ASCs downloaded software and
      protocol manuals from the OMS Web site. Centers securely submitted clinical
      information on perioperative process and outcome measures and postoperative
      patient telephone interviews. Feedback to centers ranged from current and
      historical rates of surgical and postsurgical complications to patient
      satisfaction and the adequacy of postsurgical pain relief. RESULTS: ASCs were
      able to successfully implement the data collection protocols and transmit data to
      the OMS. Data security efforts were successful in preventing the transmission of
      patient identifiers. Feedback reports to ASCs were used to institute changes in
      ASC staffing, patient care, and patient education, as well as for accreditation
      and marketing. The demonstration also pointed out shortcomings in the OMS, such
      as the need to simplify hardware and software installation as well as data
      collection and transfer methods, which have been addressed in subsequent OMS
      versions. DISCUSSION: Internet-based benchmarking for geographically dispersed
      outpatient health care facilities, such as ASCs, is feasible and likely to play a
      major role in this effort.

PMID- 10934637
TI  - Physician participation in TQM in geriatric medicine.
AB  - BACKGROUND: Quality improvement (QI) approaches such as total quality management
      (TQM) and continuous quality improvement (CQI) have great potential for improving
      the care provided to older people. Geriatricians have the necessary experience
      and skills to initiate and lead these QI efforts. A national sample of practicing
      geriatricians was surveyed in 1998 regarding involvement in, satisfaction with,
      and insights regarding TQM processes in four care settings. RESULTS: Of 537
      questionnaires returned in time for analysis, 497 were included for analysis
      after omitting questionnaires that were undeliverable or unusable (n = 25) and
      those from respondents who worked fewer than 20 hours per week (n = 15). More
      than one-third of the respondents (37.1%) reported no TQM activity at all. For
      the remainder, the primary site for TQM activity was the nursing home (33.0%),
      the hospital (22.5%), the office (11.4%), and the patient's home (3.7%). A
      majority of the respondents spent two hours per week or less on TQM projects.
      Planning an intervention and acting to maintain it in practice after its
      evaluation were the two stages of the improvement cycle these respondents engaged
      in most frequently. DISCUSSION: More geriatricians should be encouraged to
      participate in TQM training and in specific projects to improve systems of care
      for older people. Incentives to increase participation should be made available.
      Rapid-cycle improvement may fit better with physicians' culture of working for
      outcomes that have relatively short turnaround times.

PMID- 10934638
TI  - Implementing CQI projects in hospitals.
AB  - BACKGROUND: Quality improvement approaches such as continuous quality improvement
      (CQI) and total quality management are widely used, but little is known about how
      much it costs to use the principles and techniques required to implement CQI
      processes. In the Robert Wood Johnson Foundation's Improving the Quality of
      Hospital Care (IQHC) program, four consortia of hospitals were funded in the
      early 1990s. Interviews with quality managers at 38 of the consortia hospitals
      were conducted in 1995 to determine the costs of conducting CQI projects to allow
      an estimation of the marginal cost of using CQI processes (particularly cross
      disciplinary teams) to improve quality of care. CQI PROJECTS: Quality managers
      described 69% of project outcomes as critical to clinical services. Team members
      identified the issues their teams addressed and selected the project 64% of the
      time, the methods of analysis 87% of the time, and the approaches to resolving
      the problem or issue 97% of the time. Most of the respondents agreed that the
      team members had the authority to resolve the problem without appealing to higher
      levels of management. Costs for hospitals' most recently completed projects
      varied widely, from $148 for the entire project to $18,590. The length or
      duration of the projects also varied widely, from 1 month to 66 months.
      DISCUSSION: In the hospitals included in this sample, all of which were highly
      self-selected (evidenced by their participation in a voluntary consortium of
      hospitals focused on quality of care), knowledge of CQI processes appeared to be
      fairly thorough. Teams appeared to have a reasonable amount of autonomy. New CQI
      projects should be subjected to scrutiny in terms of their likely contribution to
      quality of care, as distinct from other positive outcomes.

PMID- 10934639
TI  - Using a SANE interdisciplinary approach to care of sexual assault victims.
AB  - BACKGROUND: Many hospitals have recognized the need to develop policies and
      procedures for female sexual assault victims' prompt access to emergency medical
      care and for collecting law enforcement evidence. At Lehigh Valley Hospital
      (Allentown, Penn), care in the emergency department (ED) for sexual assault
      victims was covered by oncall obstetricians and gynecologists. Although many
      aspects of rape management were in place, a busy ED with varying levels of
      physician response and exposure to the process of rape management contributed to
      a lack of standardized, objective, timely, and compassionate medical management
      of sexual assault victims. DEVELOPING THE PROGRAM: The Sexual Assault Nurse
      Examiner (SANE) interdisciplinary approach to care of sexual assault victims was
      implemented in May 1998. Community education and awareness projects emphasized
      prevention of sexual assault and domestic violence, as well as minimization of
      trauma for victims by promoting services that provide a supportive, caring, and
      healing environment. RESULTS: Comparing a baseline group of 130 sexual assault
      victims with 39 patients who were evaluated after the SANE approach was
      implemented indicated increased clinical interaction and significant improvements
      in quality indicators, such as completeness of evaluation and information
      gathered relevant to medical-legal issues. DISCUSSION: Law enforcement staff
      developed a more collaborative relationship with SANE examiners through the
      interdisciplinary team approach. Collaborative relationships were initiated with
      several other hospitals in the hospital's integrated delivery system to help
      offset some of the program's training, continuing education, and on-call costs
      and to allow for joint outcomes collection. The SANE program became a core ED
      service in July 1999.

PMID- 10934640
TI  - High bone mass in a female Hutterite population.
AB  - We examined a Hutterite population (n = 243) to determine if their agriculturally
      diverse, self-sufficient communal lifestyle promotes optimal bone mass attainment
      because of adequate calcium intake and high physical activity levels during
      growth and young adulthood. We measured total body (TB) and lumbar bone mineral
      content (BMC) and bone mineral density (BMD) in 39 school-age (younger) females
      and 204 working (older) females. Forty-five percent of older females and 79% of
      younger females currently consumed > or = 3 servings (svg) of dairy per day.
      Older females had lumbar (0.6 +/- 1.3) and TB (1.1 +/- 1.1) BMD Z scores greater
      than 0 (both, p < 0.001). The lumbar BMD Z score of younger females was not
      different from 0 (-0.1 +/- 1.0; p = 0.5). Both lumbar (r = 0.46; p < 0.001) and
      TB (r = 0.20; p = 0.02) BMD Z scores increased with increasing age. In multiple
      regression analyses for older females, lumbar bone area (p < 0.001), weight (p <
      0.001), current hours on feet per day (p = 0.01), colony workload (p < 0.01), and
      estrogen status (p = 0.06) predicted lumbar BMC. TB bone area (p < 0.001),
      current hours on feet per day (p < 0.001), and colony workload (p < 0.01)
      predicted TB BMC. For younger females, lumbar bone area (p < 0.001), weight (p <
      0.01), years in present colony (p = 0.02), and menses (p < 0.001) predicted
      lumbar BMC. TB bone area (p < 0.001), height (p < 0.01), years in present colony
      (p = 0.03), and menses (p < 0.01) predicted TB BMC. The effect of colony workload
      could not be separated from other factors different by colony. A heritability
      estimate of 0.66 was calculated for lumbar BMD using mother and daughter Z
      scores. Adequate calcium intake during growth, high physical activity early in
      life, and genetic factors may be contributing to above normal BMD levels in adult
      female Hutterites.

PMID- 10934641
TI  - Exercise, dietary calcium, and bone gain in girls and young adult women.

PMID- 10934642
TI  - Developmental expression and tissue distribution of Phex protein: effect of the
      Hyp mutation and relationship to bone markers.
AB  - Mutations in PHEX, a phosphate-regulating gene with homology to endopeptidases on
      the X chromosome, are responsible for X-linked hypophosphatemia (XLH). The murine
      Hyp homologue has the phenotypic features of XLH and harbors a large deletion in
      the 3' region of the Phex gene. We characterized the developmental expression and
      tissue distribution of Phex protein, using a monoclonal antibody against human
      PHEX, examined the effect of the Hyp mutation on Phex expression, and compared
      neprilysin (NEP), osteocalcin, and parathyroid hormone/parathyroid hormone
      related protein (PTH/PTHrP) receptor gene expression in bone of normal and Hyp
      mice. Phex encodes a 100- to 105-kDa glycoprotein, which is present in bones and
      teeth of normal mice but not Hyp animals. These results were confirmed by in situ
      hybridization (ISH) and ribonuclease protection assay. Phex protein expression in
      femur and calvaria decreases with age, suggesting a correlation between Phex
      expression and bone formation. Immunohistochemical studies detected Phex protein
      in osteoblasts, osteocytes, and odontoblasts, but not in osteoblast precursors.
      In contrast to Phex, the abundance of NEP messenger RNA (mRNA) and protein is not
      significantly altered in Hyp bone. Similarly, osteocalcin and PTH/PTHrP receptor
      gene expression are not compromised in bone of Hyp mice. Our results are
      consistent with the hypothesis that loss of Phex function affects the
      mineralizing activity of osteoblasts rather than their differentiation.

PMID- 10934643
TI  - The effects of bone marrow transplantation on X-linked hypophosphatemic mice.
AB  - The genes responsible for X-linked hypophosphatemic (XLH) vitamin D-resistant
      rickets and the murine homolog, hypophosphatemic mice (Hyp), were identified as
      PHEX and Phex (phosphate-regulating gene with homology to endopeptidases on the X
      chromosome), respectively. However, the mechanism by which inactivating mutations
      of PHEX cause XLH remains unknown. We investigated the mechanisms by syngeneic
      bone marrow transplantation (BMT) from wild mice to Hyp mice. The expression of
      the Phex gene was detected in mouse BM cells. BMT introduced a chimerism in
      recipient Hyp mice and a significant increase in the serum phosphorus level. The
      renal sodium phosphate cotransporter gene expression was significantly increased.
      The effect of BMT on the serum phosphorus level depended on engraftment
      efficiencies, which represent the dosage of normal gene. Similarly, the serum
      alkaline phosphatase (ALP) activity was decreased and bone mineral density was
      increased. Furthermore, the renal expression of 25-hydroxyvitamin D3 24
      hydroxylase, which is a key enzyme in the catabolic pathway and is increased in
      XLH/Hyp, was improved. From these results, we conclude that transplantation of
      normal BM cells improved abnormal bone mineral metabolism and deranged vitamin D
      metabolism in Hyp by replacing defective gene product(s) with normal gene
      product(s). This result may provide strong evidence for clinical application of
      BMT in metabolic bone disorders.

PMID- 10934644
TI  - Fibroblastic stromal cells express receptor activator of NF-kappa B ligand and
      support osteoclast differentiation.
AB  - Osteoclast formation in bone is supported by osteoblasts expressing receptor
      activator of NF-kappa B ligand (RANKL) and macrophage colony-stimulating factor
      (M-CSF) expression. Numerous osteotropic factors regulate expression levels of
      RANKL and the RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts, thereby
      affecting osteoclast differentiation. However, not only in RANKL widely expressed
      in soft tissues, but osteoclasts have been noted in extraskeletal lesions. We
      found that cultured skin fibroblastic cells express RANKL, M-CSF, and OPG
      messenger (mRNA). Stimulation by 1 alpha,25 dihydroxyvitamin D3 [1,25(OH)2D3]
      plus dexamethasone (Dex) augmented RANKL and diminished OPG mRNA expression in
      fibroblastic cells and caused the formation of numerous osteoclasts in cocultures
      of skin fibroblastic cells with hemopoietic cells or monocytes. The osteoclasts
      thus formed expressed tartrate-resistant acid phosphatase (TRAP) and calcitonin
      (CT) receptors and formed resorption pits in cortical bone. Osteoclast formation
      also was stimulated (in the presence of Dex) by prostaglandin E2 (PGE2),
      interleukin-11 (IL-11), IL-1, tumor necrosis factor-alpha (TNF-alpha), and
      parathyroid hormone-related protein (PTHrP), factors which also stimulate
      osteoclast formation supported by osteoblasts. In addition, granulocyte
      macrophage-CSF (GM-CSF), transforming growth factor-beta (TGF-beta), and OPG
      inhibited osteoclast formation in skin fibroblastic cell-hemopoietic cell
      cocultures; CT reduced only osteoclast nuclearity. Fibroblastic stromal cells
      from other tissues (lung, respiratory diaphragm, spleen, and tumor) also
      supported osteoclast formation. Thus, RANKL-positive fibroblastic cells in
      extraskeletal tissues can support osteoclastogenesis if osteolytic factors and
      osteoclast precursors are present. Such mesenchymally derived cells may play a
      role in pathological osteolysis and may be involved in osteoclast formation in
      extraskeletal tissues.

PMID- 10934645
TI  - Protein geranylgeranylation is required for osteoclast formation, function, and
      survival: inhibition by bisphosphonates and GGTI-298.
AB  - Bisphosphonates are the important class of antiresorptive drugs used in the
      treatment of metabolic bone diseases. Although their molecular mechanism of
      action has not been fully elucidated, recent studies have shown that the nitrogen
      containing bisphosphonates can inhibit protein prenylation in macrophages in
      vitro. In this study, we show that the nitrogen-containing bisphosphonates
      risedronate, zoledronate, ibandronate, alendronate, and pamidronate (but not the
      non nitrogen-containing bisphosphonates clodronate, etidronate, and tiludronate)
      prevent the incorporation of [14C]mevalonate into prenylated (farnesylated and
      geranylgeranylated) proteins in purified rabbit osteoclasts. The inhibitory
      effect of nitrogen-containing bisphosphonates on bone resorption is likely to
      result largely from the loss of geranylgeranylated proteins rather than loss of
      farnesylated proteins in osteoclasts, because concentrations of GGTI-298 (a
      specific inhibitor of geranylgeranyl transferase I) that inhibited protein
      geranylgeranylation in purified rabbit osteoclasts prevented osteoclast formation
      in murine bone marrow cultures, disrupted the osteoclast cytoskeleton, inhibited
      bone resorption, and induced apoptosis in isolated chick and rabbit osteoclasts
      in vitro. By contrast, concentrations of FTI-277 (a specific inhibitor of
      farnesyl transferase) that prevented protein farnesylation in purified rabbit
      osteoclasts had little effect on osteoclast morphology or apoptosis and did not
      inhibit bone resorption. These results therefore show the molecular mechanism of
      action of nitrogen-containing bisphosphonate drugs in osteoclasts and highlight
      the fundamental importance of geranylgeranylated proteins in osteoclast formation
      and function.

PMID- 10934646
TI  - Identification and characterization of the new osteoclast progenitor with
      macrophage phenotypes being able to differentiate into mature osteoclasts.
AB  - Osteoclasts are thought to belong to a macrophage lineage. However, the nature of
      common precursors of osteoclasts and macrophages remains to be investigated. We
      have characterized the differentiation potential of mouse bone marrow macrophages
      into mature osteoclasts. Monocyte macrophage-colony-stimulating factor (M-CSF)
      stimulated the proliferation of bone marrow macrophages in a dose-dependent
      manner and these M-CSF-dependent bone marrow macrophage (MDBM) cells efficiently
      differentiated into the tartrate-resistant acid phosphatase (TRAP)-positive
      osteoclasts in the presence of soluble RANKL (sRANKL) and M-CSF in the in vitro
      culture. The macrophage-like cell line TMC16 was established from tsA58
      (temperature-sensitive SV40 large T-antigen) transgenic mice in the same manner
      to the preparation of MDBM cells and also differentiated into mature osteoclasts.
      During this differentiation in vitro, the morphology of the cells changed from
      spindle to round and smaller (termed pOC) on day 2 and to multinuclear (termed
      multinucleated cells [MNCs]) on day 4. The surface expression of macrophage
      marker CD14 was down-regulated and that of CD43 was up-regulated on pOC, analyzed
      by flow cytometry. RNA analysis revealed that osteoclast marker genes such as
      calcitonin receptor (CTR), carbonic anhydrase II (CAII), cathepsin K (cath K),
      MMP9, and TRAP were strongly expressed in MNCs and weakly in pOC whereas MDBM
      cells did not express these genes. However, the osteopontin (OPN) gene was
      strongly expressed in MDBM cells and this expression became weakened after
      differentiation into pOC. The TMC16 cell line weakly expressed cath K, TRAP, and
      OPN, suggesting that the TMC16 cell line is immortalized at a stage slightly
      differentiated from MDBM cells. Furthermore, cell sorting analysis revealed that
      osteoclast early progenitors in bone marrow cells are preferentially present in
      the Mac-1- F4/80dull population, which differentiated into MDBM cells (the
      osteoclast progenitor) expressing Mac-1+ F4/80int, suggesting that M-CSF plays
      roles of a differentiation factor as well as a growth factor for osteoclast early
      progenitors. These results showed the transition of morphology, surface markers,
      and gene expression from the early to mature stage in osteoclast differentiation.
      We propose three differentiation stages in the osteoclast lineage: the pro
      osteoclast (spindle-shaped macrophage cells), the pre-osteoclast (small round
      mononucleated TRAP-positive cells), and the mature osteoclast (multinucleated
      TRAP-positive cells) stage.

PMID- 10934647
TI  - EXT 1 gene mutation induces chondrocyte cytoskeletal abnormalities and defective
      collagen expression in the exostoses.
AB  - Hereditary multiple exostoses (HME), an autosomal skeletal disorder characterized
      by cartilage-capped excrescences, has been ascribed to mutations in EXT 1 and EXT
      2, two tumor suppressor-related genes encoding glycosyltransferases involved in
      the heparan sulfate proteoglycan (HSPG) biosynthesis. Taking advantage of the
      availability of three different exostoses from a patient with HME harboring a
      premature termination codon in the EXT 1 gene, morphological, immunologic, and
      biochemical analyses of the samples were carried out. The cartilaginous
      exostosis, when compared with control cartilage, exhibited alterations in the
      distribution and morphology of chondrocytes with abundant bundles of actin
      filaments indicative of cytoskeletal defects. Chondrocytes in the exostosis were
      surrounded by an extracellular matrix containing abnormally high amounts of
      collagen type X. The unexpected presence of collagen type I unevenly distributed
      in the cartilage matrix further suggested that some of the hypertrophic
      chondrocytes detected in the cartilaginous caps of the exostoses underwent
      accelerated differentiation. The two mineralized exostoses presented lamellar
      bone arrangement undergoing intense remodeling as evidenced by the presence of
      numerous reversal lines. The increased electrophoretic mobility of chondroitin
      sulfate and dermatan sulfate proteoglycans (PGs) extracted from the two bony
      exostoses was ascribed to an absence of the decorin core protein. Altogether,
      these data indicate that EXT mutations might induce a defective endochondral
      ossification process in exostoses by altering actin distribution and chondrocyte
      differentiation and by promoting primary calcification through decorin removal.

PMID- 10934648
TI  - Integrin and mechanosensitive ion channel-dependent tyrosine phosphorylation of
      focal adhesion proteins and beta-catenin in human articular chondrocytes after
      mechanical stimulation.
AB  - Mechanical forces influence chondrocyte metabolism and function. We have
      previously shown that 0.33 Hz cyclical pressure-induced strain (PIS) results in
      membrane hyperpolarization of normal human articular chondrocytes (HAC) by
      activation of Ca(2+)-dependent K+ small conductance potassium activated calcium
      (SK) channels. The mechanotransduction pathway involves alpha 5 beta 1-integrin,
      stretch-activated ion channels (SAC) actin cytoskeleton and tyrosine protein
      kinases, with subsequent release of the chondroprotective cytokine interleukin-4
      (IL-4). The objective of this study was to examine in detail tyrosine
      phosphorylation events in the mechanotransduction pathway. The results show
      tyrosine phosphorylation of three major proteins, p125, p90, and p70 within 1
      minute of onset of mechanical stimulation. Immunoblotting and immunoprecipitation
      show these to be focal adhesion kinase (pp125FAK), beta-catenin, and paxillin,
      respectively. Tyrosine phosphorylation of all three proteins is inhibited by RGD
      containing oligopeptides and gadolinium, which is known to block SAC. beta
      catenin coimmunoprecipitates with FAK and is colocalized with alpha 5-integrin
      and pp125FAK. These results indicate a previously unrecognized role for an
      integrin-beta-catenin signaling pathway in human articular chondrocyte (HAC)
      responses to mechanical stimulation.

PMID- 10934649
TI  - Mice lacking the plasminogen activator inhibitor 1 are protected from trabecular
      bone loss induced by estrogen deficiency.
AB  - Bone turnover requires the interaction of several proteases during the resorption
      phase. Indirect evidence suggests that the plasminogen activator/plasmin pathway
      is involved in bone resorption and turnover, and recently we have shown that this
      cascade plays a role in the degradation of nonmineralized bone matrix in vitro.
      To elucidate the role of the plasminogen activator inhibitor 1 (PAI-1) in bone
      turnover in vivo, bone metabolism was analyzed in mice deficient in the
      expression of PAI-1 gene (PAI-1-/-) at baseline (8-week-old mice) and 4 weeks
      after ovariectomy (OVX) or sham operation (Sham) and compared with wild-type (WT)
      mice. PAI-1 inactivation was without any effect on bone metabolism at baseline or
      in Sham mice. However, significant differences were observed in the response of
      WT and PAI-1-/- mice to ovariectomy. The OVX WT mice showed, as expected,
      decreased trabecular bone volume (BV/TV) and increased osteoid surface (OS/BS)
      and bone formation rate (BFR), as assessed by histomorphometric analysis of the
      proximal tibial metaphysis. In contrast, no significant change in any of the
      histomorphometric variables studied was detected in PAI-1-/- mice after
      ovariectomy. As a result, the OVX PAI-1-/- had a significantly higher BV/TV,
      lower OS/BS, lower mineral apposition rate (MAR) and BFR when compared with the
      OVX WT mice. However, a comparable decrease in the cortical thickness was
      observed in OVX PAI-1-/- and WT mice. In addition, the cortical mineral content
      and density assessed in the distal femoral metaphysis by peripheral quantitative
      computed tomography (pQCT), decreased significantly after ovariectomy, without
      difference between PAI-1-/- mice and WT mice. In conclusion, basal bone turnover
      and bone mass are only minimally affected by PAI-1 inactivation. In conditions of
      estrogen deficiency, PAI-1 inactivation protects against trabecular bone loss but
      does not affect cortical bone loss, suggesting a site-specific role for PAI-1 in
      bone turnover.

PMID- 10934650
TI  - Six-month daily administration of parathyroid hormone and parathyroid hormone
      related protein peptides to adult ovariectomized rats markedly enhances bone mass
      and biomechanical properties: a comparison of human parathyroid hormone 1-34,
      parathyroid hormone-related protein 1-36, and SDZ-parathyroid hormone 893.
AB  - Daily administration of parathyroid hormone (PTH) and PTH-related protein (PTHrP)
      peptides has been shown to increase bone mass and strength in animals and, for
      PTH, to increase bone mass in humans. Long-term direct comparison of multiple
      members of the PTH/PTHrP family in vivo has not been reported. We therefore
      selected three PTH/PTHrP molecules for direct comparison in vivo in an adult rat
      model of postmenopausal osteoporosis: PTH(1-34), PTHrP(1-36), and the PTH analog,
      SDZ-PTH 893 ?Leu8, Asp10, Lys11, Ala16, Gln18, Thr33, Ala34 human PTH 1-34
      [hPTH(1-34)]?. A 6-month study was performed in which adult (6-month-old) vehicle
      treated ovariectomized (OVX) and sham OVX rats were compared with OVX rats
      receiving 40 micrograms/kg per day of either PTH(1-34), PTHrP(1-36), or PTH-SDZ
      893. Bone mass, as assessed by ash weight and densitometry, bone
      histomorphometry, biomechanical properties at trabecular and cortical sites, and
      indices of bone formation markedly increased in all three PTH/PTHrP peptide
      treated groups as compared with controls. In general, this improvement followed a
      rank order of SDZ-PTH-893 > PTH > PTHrP. The adverse effect profile also was
      greatest with SDZ-PTH-893; these rats developed moderate hypercalcemia, marked
      renal calcium accumulation, and displayed a 13% mortality. These studies show
      that PTH(1-34), PTHrP(1-36), and PTH-SDZ-893 significantly and progressively
      increase bone mass and bone strength in this rat model of postmenopausal
      osteoporosis. The adverse effect profile correlates in general terms with
      efficacy. All three peptides show promise as skeletal anabolic agents. Further
      studies in humans will be required to define optimal efficacy-to-adverse effect
      ratios and relative efficacy for each peptide in human osteoporosis.

PMID- 10934651
TI  - Biochemical markers of bone turnover, endogenous hormones and the risk of
      fractures in postmenopausal women: the OFELY study.
AB  - The mechanisms leading to increased bone loss and skeletal fragility in women
      with postmenopausal osteoporosis are still poorly understood. Increased bone
      resorption, low serum estradiol and high serum sex-hormone-binding globulin
      (SHBG) recently have been reported as predictors of vertebral and hip fractures
      in elderly women. In a cohort of healthy untreated younger postmenopausal women
      aged 50-89 years (mean, 64 years), we compared baseline levels of bone markers
      and endogenous hormones in 55 women who subsequently had a fracture (20 vertebral
      and 35 peripheral fractures) with levels in the 380 women who did not fracture
      during a mean 5 years of follow-up. Women with levels in the highest quartile of
      four bone resorption markers including urinary-free deoxypyridinoline (D-Pyr),
      urinary type I collagen N-telopeptides (NTX), and urinary and serum type I
      collagen C-telopeptides (CTX) had about a 2-fold increased risk of fractures
      compared with women with levels in the three lowest quartiles with relative risk
      (RR) and 95% CI of 1.8 (1.0-3.4) for free D-Pyr, 1.7 (0.9-3.2) for urinary NTX,
      2.3 (1.3-4.1) for urinary CTX, and 2.1 (1.2-3.8) for serum CTX. Serum levels of
      bone alkaline phosphatase (BAP) in the highest quartile were associated with an
      RR of fracture of 2.4 (1.3-4.2). Women with serum levels of estradiol and
      dehydroepiandrosterone (DHEA) sulfate in the lowest quartile had an RR of
      fracture of 2.2 (1.2-4.0) and 2.1 (1.2-3.8), respectively. Increased levels of
      SHBG and intact parathyroid hormone (PTH) were moderately associated with an
      increased risk of fracture. Similar results were obtained when the analysis was
      restricted to symptomatic vertebral and nonvertebral fractures. Adjustment of
      biochemical markers by hormone levels did not significantly alter the results.
      Women with both high bone resorption markers and low estradiol (or low DHEA
      sulfate) had a higher risk of fracture with RRs of 3.0-3.3 (p < 0.001). After
      adjustment for bone mineral density (BMD) of the hip, spine, radius, or total
      body, bone markers and hormones were still predictive of fracture risk with
      similar RRs. We conclude that high levels of some biochemical markers of bone
      turnover, low serum estradiol, low DHEA sulfate, high SHBG, and high PTH are
      associated with increased risk of osteoporotic fracture in postmenopausal women,
      independently of each other and of BMD. The mechanism by which some
      postmenopausal women have an increased rate of bone turnover leading to an
      increased risk of fracture remains to be elucidated.

PMID- 10934652
TI  - The predictive value of biochemical markers of bone turnover for bone mineral
      density in postmenopausal Japanese women.
AB  - To examine the predictive value of biochemical markers of bone turnover for bone
      loss pre- and postmenopausally, we measured two markers of bone formation, bone
      specific alkaline phosphatase (BALP) and intact osteocalcin (OC); four markers of
      bone resorption, urinary cross-linked N-telopeptides of type I collagen (NTx),
      type I collagen C-telopeptide breakdown products (CTx), hydroxylysylpyridinoline
      (HP) and lysylpyridinoline (LP); serum OC N-terminal (OC-N); and two serum
      cytokines, soluble interleukin-6 receptor (sIL-6R) and IL-1r antagonist at
      baseline and 1 year, as well as lumbar spine bone mineral density (BMD) at
      baseline and 1, 2, 3, 4, and 5 years after trial in 82 premenopausal (44.8 +/-
      5.4 years old) and 325 postmenopausal (60.2 +/- 6.1 years old) healthy Japanese
      women. In premenopausal women, stratification of the baseline value of each
      biochemical marker into quartiles did not cause any significant difference in the
      change in BMD. Stratification of the NTx baseline value in postmenopausal women
      showed significant differences in rate of bone loss to the first year among those
      subjects with each quartile (Q1 [0.28 +/- 0.28%], Q2 [-0.32 +/- 0.34%], Q3 [-1.50
      +/- 0.31%], and Q4 [-2.43 +/- 0.35%]) except for the difference between Q1 and
      Q2. The predictive value of NTx for BMD was greater in early postmenopausal women
      within 5 years after menopause than in late postmenopausal women with more than 5
      years since menopause (YSM). Quartile analysis of the other biochemical markers
      and serum cytokines did not show any significant capacity for differentiating
      between bone loss rates. Moreover, when the changes in the lumbar spine BMD to
      the second and third years were stratified into quartiles by the baseline NTx,
      the ratios of bone loss to the second and the third years were significantly
      higher in those women with higher NTx (Q4; -3.15 +/- 0.56% and -4.06 +/- 0.57%,
      respectively) than in those with lower NTx (Q1; -0.74 +/- 0.44% and -1.03 +/-
      0.51%, respectively). In conclusion, baseline urinary NTx was the most sensitive
      predictor of bone loss in the lumbar spine after 1, 2, and 3 years. Markers of
      bone resorption can be used clinically to predict future BMD in postmenopausal
      women.

PMID- 10934653
TI  - Cytokines and bone loss in a 5-year longitudinal study--hormone replacement
      therapy suppresses serum soluble interleukin-6 receptor and increases interleukin
      1-receptor antagonist: the Danish Osteoporosis Prevention Study.
AB  - The proinflammatory cytokines interleukin-1 beta (IL-1 beta) and IL-6 may play a
      central role in the acceleration of postmenopausal bone loss, but observational
      studies have led to contradictory results. Estrogen-dependent changes in the
      production of IL-1 receptor antagonist (IL-1ra) and the soluble IL-6 receptor
      (sIL-6R) potentially modify cytokine bioactivity. We therefore assessed the
      impact of menopause and hormone replacement therapy (HRT) on cytokines and
      activity modifiers in serum within a 5-year longitudinal study. One hundred sixty
      perimenopausal women (age 50.1 +/- 2.8 years) were randomized to HRT or no
      treatment. Serum IL-6 increased with age (r = 0.16; p < 0.05), but cytokines did
      not correlate with baseline bone mineral density (BMD). HRT led to small
      increases in IL-1ra (p < 0.001) and IL-6 (p < 0.05), with a decrease in sIL-6R (p
      < 0.01) and no change in IL-1 beta. No changes were observed in the control
      group. IL-1ra was inversely correlated with bone loss at the ultradistal forearm
      (r = 0.29; p < 0.05) and to a lesser degree at the spine (r = 0.20; p = 0.09). In
      addition, there was a weak positive correlation between sIL-6R and bone loss at
      the ultradistal forearm (r = 0.26; p < 0.05). High IL-6 levels were associated
      with slower bone loss (spine r = 0.31, p < 0.01) and controlling for age did not
      diminish this association. The percent change in sIL-6R during HRT was correlated
      with the bone loss at the femoral neck (r = -0.29; p < 0.01) and weakly with bone
      loss in the spine (r = -0.16; p = 0.17). In conclusion, serum IL-1ra and sIL-6R
      are influenced by HRT and are associated with the rate of bone loss in
      perimenopausal women.

PMID- 10934654
TI  - Dietary protein deficiency induces osteoporosis in aged male rats.
AB  - Low dietary intake is common in elderly males with low femoral neck areal bone
      mineral density (BMD). To evaluate the selective influence of a low-protein diet
      in the pathogenesis of osteoporosis in males and to uncover early and late
      adaptation of bone cells to protein deficiency, 8-month-old male rats were pair
      fed a control (15% casein) or isocaloric low-protein (2.5% casein) diet for 1 or
      7 months. BMD, bone ultimate strength, stiffness, and absorbed energy were
      measured in tibia proximal metaphysis and diaphysis. After double-labeling,
      histomorphometric analysis was performed at the same sites. Serum osteocalcin,
      insulin-like growth factor I (IGF-I), and urinary deoxypyridinoline excretion
      were measured. In proximal tibia, isocaloric low-protein diet significantly
      decreases BMD (12%), cancellous bone mass (71%), and trabecular thickness (Tb.Th;
      30%), resulting in a significant reduction in ultimate strength (27%). In
      cortical middiaphysis, a low-protein diet decreases BMD (9%) and enlarges the
      medullary cavity (36%), leading to cortical thinning and lower mechanical
      strength (20%). In cancellous bone, protein deficiency transiently depresses the
      bone formation rate (BFR; 60%), osteoid seam thickness (15%), and mineral
      apposition rate (MAR; 20%), indicating a decrease in osteoblast recruitment and
      activity. Cortical loss (15%) results from an imbalance between endosteal
      modeling drifts with impaired BFR (70%). From the first week of protein
      deficiency, osteocalcin and IGF-I levels drop significantly. Bone resorption
      activity and urinary deoxypyridinoline remain unchanged throughout the
      experiment. Protein deficiency in aged male rats induces cortical and trabecular
      thinning, and decreases bone strength, in association with a remodeling imbalance
      with a bone formation impairment and a decrease in IGF-I levels.

PMID- 10934655
TI  - Consequences of vertebral deformities in older men and women.
AB  - The objectives of this study were to ascertain the prevalence of the number and
      severity of vertebral deformities in elderly people and determine the extent to
      which these are associated with several aspects of functioning. The study was
      conducted in a subsample of the Longitudinal Aging Study Amsterdam (LASA)
      consisting of 527 participants (260 men and 267 women), aged 65 years or over.
      Lateral radiographs of the spine (T4-L5) were made of each participant and a
      semiquantitative method was used to assess the number and degree of vertebral
      deformities. The prevalence of having at least one vertebral deformity was 39% in
      both men and women. Six percent of the men and 5% of the women had at least three
      vertebral deformities. For severe deformities, the prevalence was 8% in men and
      12% in women. The number of vertebral deformities was significantly associated
      with a height loss of more than 5 cm, difficulties in activities of daily living,
      poor performance, more than 3 days in bed and more than 3 days with limited
      activities because of health problems in the past month, and poor self-perceived
      health. For most of these outcome measures, associations were strongest when
      three or more deformities were present. The presence of a severe deformity was
      associated with a height loss of more than 5 cm, poor performance, more than 3
      days with limited activities in the past month, and poor self-perceived health.
      None of the associations between number and severity of vertebral deformities and
      the level of functioning was modified by sex. We can conclude that vertebral
      deformities are very common in both older men and older women and that vertebral
      deformities, even if they are not clinically manifest, have a substantial impact
      on the level of functioning and well-being of older people.

PMID- 10934656
TI  - Interpretation of calcaneus dual-energy X-ray absorptiometry measurements in the
      assessment of osteopenia and fracture risk.
AB  - Dual-energy X-ray absorptiometry (DXA) of the calcaneus is useful in assessing
      bone mass and fracture risk at other skeletal sites. However, DXA yields an areal
      bone mineral density (BMD) that depends on both bone apparent density and bone
      size, potentially complicating interpretation of the DXA results. Information
      that is more complete may be obtained from DXA exams by using a volumetric
      density in addition to BMD in clinical applications. In this paper, we develop a
      simple methodology for determining a volumetric bone mineral apparent density
      (BMAD) of the calcaneus. For the whole calcaneus, BMAD = (BMC)/ADXA3/2, where BMC
      and ADXA are, respectively, the bone mineral content and projected area measured
      by DXA. We found that ADXA3/2 was proportional to the calcaneus volume with a
      proportionality constant of 1.82 +/- 0.02 (mean +/- SE). Consequently, consistent
      with theoretical predictions, BMAD was proportional to the true volumetric
      apparent density (rho) of the bone according to the relationship rho = 1.82 BMAD.
      Also consistent with theoretical predictions, we found that BMD varied in
      proportion to rho V1/3, where V is the bone volume. We propose that the
      volumetric apparent density, estimated at the calcaneus, provides additional
      information that may aid in the diagnosis of osteopenia. Areal BMD or BMD2 may
      allow estimation of the load required to fracture a bone. Fracture risk depends
      on the loading applied to a bone in relation to the bone's failure load. When DXA
      is used to assess osteopenia and fracture risk in patients, it may be useful to
      recognize the separate and combined effects of applied loading, bone apparent
      density, and bone size.

PMID- 10934657
TI  - Low-level cadmium exposure and osteoporosis.
AB  - Osteoporosis is a major cause of morbidity worldwide. A number of risk factors,
      such as age and gender, are well established. High cadmium exposure causes renal
      damage and in severe cases also causes osteoporosis and osteomalacia. We have
      examined whether long-term low-level cadmium exposure increases the risk of
      osteoporosis. Bone mineral density (BMD) in the forearm was measured in 520 men
      and 544 women, aged 16-81 years, environmentally or occupationally exposed to
      cadmium, using dual-energy X-ray absorptiometry (DXA) technique. Cadmium in urine
      was used as the dose estimate and protein HC was used as a marker of renal
      tubular damage. There was a clear dose-response relation between cadmium dose and
      the prevalence of tubular proteinuria. Inverse relations were found between
      cadmium dose, tubular proteinuria, and BMD, particularly apparent in persons over
      60 years of age. There was a dose-response relation between cadmium dose and
      osteoporosis. The odds ratios (ORs) for men were 2.2 (95% CI, 1.0-4.8) in the
      dose group 0.5-3 nmol Cd/mmol creatinine and 5.3 (2.0-14) in the highest dose
      category (> or = 3 nmol/mmol creatinine) compared with the lowest dose group (<
      0.5 nmol Cd/mmol creatinine). For women, the OR was 1.8 (0.65-5.3) in the dose
      group 0.5-3 nmol Cd/mmol creatinine. We conclude that exposure to low levels of
      cadmium is associated with an increased risk of osteoporosis.

PMID- 10934658
TI  - Generalized low areal and volumetric bone mineral density in adolescent
      idiopathic scoliosis.
AB  - Adolescent idiopathic scoliosis (AIS) may be associated with generalized low bone
      mineral status. The bone mineral density (BMD) of 75 girls of 12-14 years of age
      and diagnosed as having AIS were compared with 94 age-matched female control
      subjects. Areal BMD (aBMD) of the lumbar spine (L2-L4) and the bilateral proximal
      femur were measured using-energy X-ray absorptiometry (DEXA), and volumetric BMD
      (vBMD) of the nondominant distal radius and bilateral distal tibias was measured
      with peripheral quantitative computer tomography (pQCT). Relevant anthropometric
      parameters and the severity of the spinal deformity (Cobb's angle) also were
      evaluated and correlated with the BMD measurements. Results revealed the presence
      of a generalized lower bone mineral status in AIS patients. Detailed analysis
      showed that the aBMD and vBMD measured at the bilateral lower extremities were
      significantly lower in AIS patients when compared with the same in the normal
      controls. The most significant effect was seen in the trabecular BMD (tBMD) of
      the distal tibias. Of all the AIS girls, 38% of the aBMD and 36% of the vBMD were
      below -1 SD of the normal. BMD was found to correlate better with "years since
      menarche" (YSM) than with chronological age. When the BMD was evaluated for the 3
      YSM groups, aBMD of the proximal femur and tBMD of distal tibias were found to be
      significantly lower in the AIS patients. Neither the aBMD nor the vBMD of AIS
      patients was found to be associated with the severity of spinal deformity. In
      addition, anthropometric measurements showed significantly longer arm span and
      lower extremities in the AIS girls. We concluded that the AIS girls had
      generalized lower aBMDs and vBMDs.

PMID- 10934659
TI  - Partitioning a daily mechanical stimulus into discrete loading bouts improves the
      osteogenic response to loading.
AB  - A single 3-minute bout of mechanical loading increases bone formation in the rat
      tibia. We hypothesized that more frequent, shorter loading bouts would elicit a
      greater osteogenic response than a single 3-minute bout. The right tibias of 36
      adult female Sprague-Dawley rats were subjected to 360 bending cycles per day of
      a 54 N force delivered in 1, 2, 4, or 6 bouts on each of the 3 loading days. Rats
      in the 6-bouts/day group received 60 bending cycles per bout (60 x 6); rats in
      the 4-bouts/day group received 90 bending cycles per bout (90 x 4); the 2- and 1
      bouts/day groups received 180 and 360 bending cycles per bout, respectively (180
      x 2 and 360 x 1). A nonloaded, age-matched control group (0 x 0) and two sham
      bending groups (60 x 6 and 360 x 1) also were included. Fluorochrome labeling
      revealed a 10-fold increase in endocortical lamellar bone formation rate
      (BFR/bone surface [BS]) in the right tibia versus the left (nonloaded) side in
      the 60 x 6 bending group. Endocortical BFR/BS in the right tibia of the 4-, 2-,
      and 1-bout bending groups exhibited 8-, 4-, and 4-fold increases, respectively,
      over the control side. Relative (right minus left) values for endocortical
      BFR/BS, mineralizing surface (MS/BS), and mineral apposition rate (MAR) were 65
      94% greater in the 90 x 4 and 60 x 6 bending groups compared to the 360 x 1
      bending group. Sham-bending tibias exhibited relative endocortical bone formation
      values similar to those collected from the control (0 x 0) group. The data show
      that 360 daily loading cycles applied at intervals of 60 x 6 or 90 x 4 represent
      a more osteogenic stimulus than 360 cycles applied all at once, and that
      mechanical loading is more osteogenic when divided into discrete loading bouts.
      Presumably, bone cells become increasingly "deaf" to the mechanical stimulus as
      loading cycles persist uninterrupted, and by allowing a rest period between
      loading bouts, the osteogenic effectiveness of subsequent cycles can be
      increased.

PMID- 10934660
TI  - Phalangeal osteosonogrammetry study: age-related changes, diagnostic sensitivity,
      and discrimination power. The Phalangeal Osteosonogrammetry Study Group.
AB  - Phalangeal osteosonogrammetry was introduced as a method for bone tissue
      investigation in 1992. It is based on the measure of the velocity of ultrasound
      (amplitude-dependent speed of sound [AD-SoS]) and on the interpretation of the
      characteristics of the ultrasound signal. In this study we have collected a
      database of 10,115 subjects to evaluate the performance of AD-SoS and to develop
      a parameter that is able to quantify the signal characteristics: ultrasound bone
      profile index (UBPI). The database only includes females of which 4.5% had
      documented vertebral osteoporotic fractures, 16% lumbar spine dual X-ray
      absorptiometry (DXA), and 6% hip DXA. The analysis of the ultrasound signal has
      shown that with aging the UBPI, first wave amplitude (FWA), and signal dynamics
      (SDy) follow a trend that is different from the one observed for AD-SoS; that is,
      there is no increase during childhood. In the whole population, the risk of
      fracture per SD decrease for AD-SOS was odds ratio (OR) 1.71 (CI, 1.58-1.84). The
      AD-SoS in fractured subjects was significantly lower than in a group of age
      matched nonfractured subjects (p < 0.0001). In a small cohort of hip-fractured
      patients UBPI proved to be lower than in a control age-matched group (p <
      0.0001). When the World Health Organization (WHO) working group criteria were
      applied to this population to identify the T score value for osteoporosis, for AD
      SoS we found a T score of -3.2 and for UBPI we found a T score of -3.14. Sixty
      six percent of vertebral fractures were below the AD-SoS -3.2 T score and 62%
      were below UBPI -3.14. We observed the highest incidence of fractures (63.6%)
      among subjects with AD-SoS who had both DXA T score values below the threshold.
      We conclude from this study that ultrasound investigation at the hand phalanges
      is a valid methodology for osteoporosis assessment. It has been possible to
      quantify signal changes by means of UBPI, a parameter that will improve the
      possibility of investigating bone structure.

PMID- 10934661
TI  - In vitro apatite induction by phosphophoryn immobilized on modified collagen
      fibrils.
AB  - Noncollagenous phosphoproteins that interact with type I collagen are thought to
      nucleate the mineral phase to collagen network of mineralized tissues.
      Previously, we found that phosphophoryn cross-linked to type I collagen was an
      effective nucleator of apatite. Here, we investigated the potential role of
      collagen telopeptide structure on this nucleation. We used pepsin and sodium
      borohydride (NaBH4) to modify the telopeptide region and reducible cross-links in
      the collagen fibrils and determined the effect on mineral induction by
      phosphophoryn cross-linked to it. The amount of phosphophoryn cross-linked to
      NaBH4-reduced collagen fibrils was higher than that to intact (unmodified)
      collagen fibrils. However, the amount of phosphophoryn cross-linked to collagen
      that lacked the telopeptides (atelocollagen) was 25% of that cross-linked to
      intact collagen fibrils. Each preparation was incubated at 37 degrees C in
      metastable calcium phosphate solutions that did not spontaneously precipitate.
      Apatite was induced by phosphophoryn cross-linked to intact collagen fibrils at
      15.0 h whereas phosphophoryn cross-linked to reduced collagen fibrils induced
      apatite formation after 10.9 h. Enough phosphophoryn was cross-linked to
      atelocollagen to induce mineral formation, but it did not. The failure of the
      phosphophoryn-atelocollagen complex to nucleate mineral might have been caused by
      a cross-linking pattern in the helical portion of the collagen molecule that did
      not promote the growth of the calcium-phosphate clusters into nuclei. The present
      study indicates that the telopeptide domains of type I collagen play a role in
      the interaction with phosphophoryn, which is critical for the nucleation process.

PMID- 10934662
TI  - Osteogenesis from cultured chick periostea has a specific requirement for
      chloride.
AB  - Bone development, like embryonic development in general, depends on a particular
      internal electrical milieu. Ions are the carriers of currents that maintain this
      internal environment. In embryonic bone, chloride is a major carrier of such
      current. To explore the role chloride plays in embryonic bone development we
      performed several ion-removal experiments, using the chick periosteal
      osteogenesis (CPO) system as our model. We found that if chloride is reduced in
      the medium and replaced with a nontoxic anion, alkaline phosphatase (ALP)
      activity does not rise, nor does osteogenic development occur. However, acid
      phosphatase (AP) activity is not affected by level of chloride. Experiments using
      metabolic inhibitors showed that explants cultured in low chloride medium remain
      viable. Dose-response studies revealed that the response of ALP activity to
      chloride concentration is sigmoidal, with a [Cl-]0.5 of 45.9 mM. Reciprocal
      transfers of explants between complete and low chloride medium show that the rise
      in ALP activity depends on the length of time explants are cultured with
      chloride. In contrast, such transfer experiments show that osteogenesis requires
      chloride only during days 2-3 of culture.

PMID- 10934664
TI  - Optimizing the science of drug development: opportunities for better candidate
      selection and accelerated evaluation in humans.
AB  - Two international meetings were convened in 1998 to review the current science of
      drug development and the potential opportunities to optimize the evaluation of
      new drugs in humans. This report represents a synopsis of these meetings, and
      focuses on the current state of knowledge pertaining to drug development, future
      scientific and technical needs, and the relative merits of various strategies
      intended to accelerate the clinical development of drugs.

PMID- 10934663
TI  - Utilization of bone morphogenetic protein receptors during chondrocyte
      maturation.
AB  - Cartilage from the upper, cephalic portion of embryonic chick sternums undergoes
      hypertrophy, while the lower, caudal portion of the sternum remains as cartilage.
      Bone morphogenetic proteins (BMPs) induce type X collagen (colX) in cultured
      upper but not lower sternal chondrocytes (LSCs). We have examined the utilization
      of BMP receptors (BMPRs) by upper sternal chondrocytes (USCs) and LSCs both by
      analyzing receptor expression and by overexpressing mutant BMPRs. Reverse
      transcription polymerase chain reaction (RT-PCR) analyses indicate that both
      upper and lower chondrocytes produce messenger RNA (mRNA) for all three
      receptors: BMPR type IA (BMPR-IA), BMPR type IB (BMPR-IB), and BMPR type II (BMPR
      II). Infection of USC with retroviral vectors expressing constitutively active
      (CA) BMPRs showed that CA-BMPR-IB, like exogenous BMP-4, induced both colX mRNA
      and elevated alkaline phosphatase (AP), while CA-BMPR-IA was markedly less
      potent. However, expression of activated receptors in LSC cultures resulted in
      only minimal induction of hypertrophic markers. Consistent with the results seen
      for CA receptors, dominant negative (DN) BMPR-IB blocked BMP-induced hypertrophy
      in USCs more effectively than DN-BMPR-IA. These results imply that the major BMPR
      required for BMP induction of chondrocyte hypertrophy is BMPR-IB, and that
      difference between permanent and prehypertrophic chondrocytes is not caused by
      absence of receptors required for BMP signaling.

PMID- 10934665
TI  - The future of clinical trials in chronic renal disease: outcome of an
      NIH/FDA/Physician Specialist Conference. Evaluation of Clinical Trial Endpoints
      in Chronic Renal Disease Study Group.
AB  - For people with chronic renal insufficiency, the therapeutic goal is to prevent
      progression to end-stage renal disease, a serious condition that can only be
      treated with dialysis and kidney transplantation. Although restriction of dietary
      protein slows the progression of renal disease somewhat, the principal treatment
      to slow chronic renal disease is appropriate reduction of blood pressure.
      Antihypertensive agents, particularly those that produce sustained, long-term
      reductions in proteinuria, such as angiotensin-converting enzyme inhibitors, not
      only decrease blood pressure but also preserve renal function. Clinical trials to
      evaluate these and other drug therapies in renal disease progression have used
      both "hard end points" (e.g., dialysis, transplantation, death) and intermediate
      end points of renal disease progression (e.g., doubling of serum creatinine
      concentration, reductions in proteinuria). Trials that have used hard end points
      typically recruited patients with advanced renal disease to demonstrate a
      difference in therapies within a period of 2 to 5 years. However, proteinuria
      reduction, along with a decrease in the time to doubling of serum creatinine in
      very early diabetic renal disease, could demonstrate an altered natural history
      of renal disease. Although hard end points are indicators of a drug's efficacy in
      reducing cardiovascular events or preserving renal function, they do not assess
      the impact of a treatment on altering the natural history of early renal disease.
      For clinical trials of people with all but the most advanced renal disease, use
      of intermediate end points of renal disease progression is the only practical
      option for assessment of treatment efficacy and effectiveness. Given the
      available data on proteinuria reduction and doubling of serum creatinine from
      clinical trials, these end points, taken together, appear to provide an
      acceptable means of assessing a treatment's impact on slowing renal disease
      progression.

PMID- 10934666
TI  - Who needs individual bioequivalence studies for narrow therapeutic index drugs? A
      case for warfarin.
AB  - Warfarin is, among drugs, considered to have a narrow therapeutic index for which
      individual bioequivalence has been suggested. To establish the propriety of
      "switching," an individual bioequivalence study involving a replicate-design
      study and three "switchings" in healthy subjects was undertaken using the U.S.
      brand warfarin sodium tablet and a generic product. A randomized, single-center,
      open-label, single-dose, four-way crossover replicate bioequivalence study was
      performed in 24 healthy male volunteers in which each subject received the same 5
      mg warfarin test and reference tablets twice on different occasions under fasting
      conditions. Concentrations of warfarin in plasma were measured by a validated
      specific HPLC method. The individual pharmacokinetic parameters obtained with
      test and reference products were compared using pooled data and Liu's method.
      Bioequivalence was shown with both average and individual bioequivalence methods.
      The individual bioequivalence assessment did not show a subject-by-formulation
      interaction, nor did it add value to the bioequivalence assessment of warfarin.

PMID- 10934668
TI  - Steady-state pharmacokinetics of carvedilol and its enantiomers in patients with
      congestive heart failure.
AB  - Carvedilol is a relatively new drug with beta- and alpha 1-receptor blocking
      activity and antioxidant effects recently approved for the treatment of
      congestive heart failure (CHF). An ascending, multiple-dose study was completed
      in 20 male patients with stable New York Heart Association (NYHA) Class III or IV
      CHF. The pharmacokinetics of carvedilol, S(-)-carvedilol, R(+)-carvedilol, and
      the active metabolites of carvedilol was assessed at steady state after twice
      daily oral administration of carvedilol for 7 days at 6.25, 12.5, 25, and 50 mg
      doses. Carvedilol exhibited stereoselective pharmacokinetics in CHF patients with
      dose-proportional increases in steady-state plasma concentrations of carvedilol
      and its enantiomers. Mean AUC and Cmax values for carvedilol were up to twofold
      higher in patients with Class IV CHF as compared to those with Class III CHF.
      Steady-state plasma concentrations of the active metabolites also increased in a
      dose-proportional manner and were typically 10% or less of that observed for
      carvedilol. In general, carvedilol was adequately tolerated by adult male CHF
      patients at the dose levels (6.25-50 mg) evaluated in this study as adverse
      events were consistent with those frequently observed in patients with CHF.

PMID- 10934667
TI  - The pharmacokinetics and tolerability of the oral neuraminidase inhibitor
      oseltamivir (Ro 64-0796/GS4104) in healthy adult and elderly volunteers.
AB  - The tolerability and pharmacokinetics of Ro 64-0802, a potent, selective
      inhibitor of influenza neuraminidase, and its oral prodrug oseltamivir were
      investigated in three double-blind, placebo-controlled studies. Two studies
      involved healthy adult volunteers (18-55 years) (n = 48) who received single (20
      1000 mg) or bid doses (50-500 mg) (n = 32) of oseltamivir or placebo for 7 days.
      Healthy elderly volunteers (> or = 65 years) (n = 24) received oseltamivir 100 to
      200 mg bid or placebo for 7 days in a third study. Measurable plasma
      concentrations of the active metabolite appeared rapidly in plasma and were
      significantly higher and longer lasting than those of oseltamivir.
      Pharmacokinetics of both compounds were linear. Multiple-dose exposure was
      predictable from single-dose data, and steady-state plasma concentrations were
      achieved within 3 days of bid drug administration. Oseltamivir was well tolerated
      at single doses of up to 1000 mg and twice-daily doses of up to 500 mg. Adverse
      events were mild in intensity. Exposure to both prodrug and active metabolite was
      increased in elderly patients by approximately 25%. However, due to the wide
      safety margin of both compounds, no dose adjustment is necessary for elderly
      patients.

PMID- 10934669
TI  - Variable absorption of carbidopa affects both peripheral and central levodopa
      metabolism.
AB  - Carbidopa (CD), a competitive inhibitor of aromatic l-amino acid decarboxylase
      that does not cross the blood-brain barrier, is routinely administered with
      levodopa (LD) to patients with Parkinson disease (PD) to reduce the peripheral
      decarboxylation of LD to dopamine. Using a stable isotope-labeled form of LD, the
      authors examined in 9 PD patients the effects of variable CD absorption on
      peripheral and central LD metabolism. Subjects were administered orally 50 mg of
      CD followed in 1 hour by a slow bolus intravenous infusion of 150 mg stable
      isotope-labeled LD (ring 1',2',3',4',5',6'-13C). Eight patients underwent a
      lumbar puncture 6 hours following the infusion. Blood and cerebrospinal fluid
      (CSF) samples were analyzed for labeled and unlabeled metabolites using a
      combination of high-performance liquid chromatography and mass spectrometry. When
      patients were divided into "slow" and "rapid" CD absorption groups, significantly
      greater peripheral LD decarboxylation (as measured by area under the curve [AUC]
      labeled serum HVA) was noted in the poor absorbers (p = 0.05, Mann-Whitney U
      test). Elimination half-lives for serum LD did not differ between groups,
      suggesting a further capacity for decarboxylation inhibition in the "rapid"
      absorbers. A significant correlation between AUC serum CD and percent-labeled HVA
      in CSF was found for all patients (R = 0.786, p = 0.02). "Rapid" as compared to
      "slow" CD absorbers had significantly more percent-labeled CSF HVA (60 vs. 49, p
      = 0.02, Mann-Whitney U test), indicating greater central-labeled DA production in
      the better CD absorbers. The data suggest that peripheral aromatic l-amino acid
      decarboxylase activity is not saturated at CD doses used in current practice. The
      authors believe that future studies to better examine a dose dependence of CD on
      peripheral LD decarboxylation and LD brain uptake are warranted.

PMID- 10934670
TI  - Pharmacokinetics of ibuprofen enantiomers in children with cystic fibrosis.
AB  - Chiral inversion of R(-)- to S(+)-ibuprofen in children with cystic fibrosis was
      investigated. Children with cystic fibrosis (n = 38, ages 2-13 years) were
      administered a single oral dose of racemic ibuprofen (20 mg/kg), and the
      pharmacokinetics of ibuprofen was found to be stereoselective. Mean Cmax, AUC,
      apparent CL/F, and Varea/F of S-ibuprofen were significantly different from those
      of R-ibuprofen. The enantiomeric ratio of plasma AUC (S:R = 2.09:1) and of free
      and conjugated ibuprofen in urine (S:R = 13.9:1) of children with cystic fibrosis
      was not different from reported values for healthy children and adults. No
      significant gender difference was observed for any of the pharmacokinetic
      parameters determined. However, there was an inverse linear relationship between
      the CL/F of R-ibuprofen and age in children with cystic fibrosis. Apparent CL/F
      was higher in children with cystic fibrosis than previously reported for healthy
      children; therefore, higher doses of ibuprofen would be necessary for children
      with cystic fibrosis.

PMID- 10934671
TI  - Pharmacokinetics of ofloxacin enantiomers after intravenous administration for
      antibiotic prophylaxis in biliary surgery.
AB  - The pharmacokinetics of S-(-)- and R-(+)-ofloxacin, enantiomers of the
      fluoroquinolone ofloxacin, were characterized after prophylactic administration
      in 15 patients undergoing elective biliary surgery. A single dose of ofloxacin
      400 mg given intravenously as an infusion was administered 1 hour before surgery.
      Plasma levels of S-(-)- and R-(+)-ofloxacin showed very small differences between
      both enantiomers, although the ratio of S-(-)- to R-(+)-enantiomer concentration
      in plasma showed significant differences (p < 0.05) at 4 and 12 hours. Adequate S
      (-)-ofloxacin (levofloxacin, the active enantiomer) plasma levels (> or = minimum
      inhibitory concentration [MIC90] for Escherichia coli) were found throughout the
      procedure. For pharmacokinetic parameters, the authors found small but
      statistically significant differences (p < 0.05) in the area under the
      concentration-time curve, AUC0-infinity (22.30 +/- 2.72 mg h/L for S-(-)
      ofloxacin vs. 20.50 +/- 2.06 mg h/L for R-(+)-ofloxacin), and in the clearance
      (0.15 +/- 0.04 L/h/Kg for S-(-)-ofloxacin vs. 0.16 +/- 0.04 L/h/Kg for R-(+)
      ofloxacin). To test the penetration of ofloxacin enantiomers into tissues, the
      authors measured levels in subcutaneous cell tissue and gall-bladder cell tissue.
      They did not observe statistical differences between the two isomers, which means
      that distribution is not an estereoselective process. Enantiomer levels in these
      two tissues decreased rapidly, but the highest concentrations were reached during
      the 4 first hours (i.e., when the surgical procedure was being performed). In
      conclusion, with the prophylactic treatment used, levofloxacin plasma and tissue
      levels are high enough to prevent surgical infections.

PMID- 10934672
TI  - Irbesartan does not affect the pharmacokinetics of simvastatin in healthy
      subjects.
AB  - This open-label, single-dose, crossover study was conducted to assess the effect
      of irbesartan on the pharmacokinetics of total simvastatin acid in 14 healthy
      subjects. Subjects were randomized to receive one simvastatin 40 mg tablet or one
      simvastatin 40 mg tablet + one irbesartan 300 mg tablet. Subjects were crossed
      over to the other treatment after a 7- to 10-day washout period. Serum samples
      were collected at specified times before and over a 24-hour period after dosing.
      Safety was assessed by monitoring vital signs, laboratory tests, and adverse
      events. Irbesartan did not exhibit a clinically significant effect on the peak
      serum concentration and area under the concentration versus time curve to
      infinity (AUC0-infinity) of total simvastatin acid. The mean AUC0-infinity of
      total simvastatin acid was 74.55 ng x h/mL when simvastatin was given alone and
      67.55 ng x h/mL when simvastatin and irbesartan were given concomitantly. The
      time to peak serum concentration for both treatments was 3 hours. No serious
      adverse events occurred during the study, and both agents were well tolerated. In
      summary, irbesartan had no significant effect on the single-dose pharmacokinetics
      of total simvastatin acid.

PMID- 10934673
TI  - Mechanism and amelioration of recombinant human interleukin-11 (rhIL-11)-induced
      anemia in healthy subjects.
AB  - Recombinant human interleukin-11 (rhIL-11), or Neumega rhIL-11 Growth Factor, is
      a recombinant cytokine that stimulates megakaryocytopoiesis, increases platelet
      production, and also has shown anti-inflammatory and immune-modulating activity.
      Mild, reversible anemia was the most common adverse event observed in clinical
      studies and was demonstrated to be related to hemodilution. The purpose of this
      study was to examine the renal mechanisms of the rhIL-11-induced volume retention
      and devise a possible therapeutic intervention to ameliorate this effect.
      Eighteen healthy volunteers (9 male and 9 female) on a controlled sodium (180
      mEq/day) and potassium (120 mEq/day) diet were randomized to one of six treatment
      sequences in a three-period crossover design. Each subject received 25
      micrograms/kg IL-11 s.c. once daily, 25 micrograms/kg IL-11 s.c. once daily +
      Maxzide-25 twice daily, or placebo for 7 days in a crossover design. There was a
      14-day washout period between treatment periods. Renal clearance parameters
      indicated that mean sodium excretion was decreased compared to placebo within 8
      hours after dosing with rhIL-11, with these results reaching statistical
      significance 8 to 16 hours postdose (p < 0.01). The cumulative sodium excretion
      (mEq +/- SD) over the 7-day treatment period for each respective treatment group
      was the following: rhIL-11 = 833 +/- 154, rhIL-11 + Maxzide-25 twice daily = 1114
      +/- 178, and placebo = 982 +/- 193 (p < 0.01). Hemoglobin concentration and
      hematocrit values, used as indicators of hemodilution, decreased in the rhIL-11
      treated group as compared to the baseline and placebo groups (p < 0.01).
      Concurrent dosing with Maxzide-25 twice daily reduced the rhIL-11-associated
      hemodilution by about 50%.

PMID- 10934674
TI  - A family-based, developmental-ecological preventive intervention for high-risk
      adolescents.
AB  - Family-based preventive intervention has emerged as a promising modality for
      preventing antisocial behavior problems in youth. This article introduces an
      intensive, family-based preventive intervention for high-risk adolescents:
      Multidimensional Family Prevention. Multidimensional Family Prevention combines
      the advantages of standard prevention models (curriculum based and protection
      focused) with those of psychosocial treatment models (assessment based and
      problem focused). The model's main features are described: theoretical
      foundations (risk and protection theory, developmental psychopathology,
      ecological theory), guidelines for constructing a multidomain prevention program
      (family and peer relationships, school and prosocial activities, drug use and
      health issues, cultural themes), and strategies for tailoring and implementing
      five flexible intervention modules (adolescent, parent, interactional, extended
      family, extrafamilial). Implemented in the family's home, the intervention works
      to create a resilient family environment that supports the basic adolescent
      developmental goals of renegotiated attachment bonds within the family and
      durable connections with prosocial institutions.

PMID- 10934675
TI  - The influence of marital and family therapy on health care utilization in a
      health-maintenance organization.
AB  - Research has shown that people reduce their use of health care after individual
      psychotherapy. However, little research has been done to learn if marital and
      family therapy has a similar effect. Subjects (n = 292) from a health-maintenance
      organization were randomly selected according to the type of therapy they had
      received. Subjects' medical records were examined for 6 months before, during,
      and after therapy. Those who received marital and family therapy significantly
      reduced their use of health care services by 21.5%. These results show an "offset
      effect" for marriage and family therapy.

PMID- 10934676
TI  - Relationship satisfaction of Mexican American and non-Hispanic white American
      interethnic couples: issues of acculturation and clinical intervention.
AB  - Despite the increasing prevalence of interethnic marriages, remarkably little
      empirical literature exists for guiding clinical interventions offered to these
      couples. This study compared the marriages of 72 couples with one Mexican
      American partner and one non-Hispanic White American partner, 75 Mexican-American
      couples, and 66 non-Hispanic White couples. Overall, the interethnic couples were
      more similar to non-Hispanic White couples than they were to Mexican-American
      couples across multiple domains, with the latter group indicating modestly higher
      levels of relationship distress. Among interethnic couples, Mexican-American
      wives' level of acculturation related significantly to both their own marital-
      and parental-role orientation and to distress in their relationships with
      children, as well as to their husbands' marital distress regarding child rearing
      and the couple's interactions regarding finances. Implications for clinical
      interventions with Mexican- and White-American interethnic couples are discussed.

PMID- 10934677
TI  - Biracial youth and families in therapy: issues and interventions.
AB  - Empirical research and clinical resources focusing specifically on minority youth
      and families have increased tremendously in the last 2 decades. Despite this
      trend, certain groups continue to be relatively neglected. In particular, very
      few resources exist for understanding the unique challenges that often face
      biracial youth and their families. In this article, we use a nationally
      representative database to compare functioning in biracial youth to white
      adolescents and other minority adolescents. Results suggest that
      biracial/biethnic youth are a particularly vulnerable group in terms of self
      reported delinquency, school problems, internalizing symptoms, and self-regard.
      As a group, they are also more likely to receive some form of psychological
      intervention. Given these findings and the shortcoming of clinical resources for
      work with this population, we provide an in-depth discussion of why biracial
      youth may be particularly vulnerable from a social-constructionist framework and
      offer several strategies based on narrative family therapy for working with
      biracial youngsters and their families.

PMID- 10934678
TI  - Gender, family competence, and psychological symptoms.
AB  - In this study (n = 197) I examine the relationship between the presence of
      individual psychological symptoms as reported on the Symptom Checklist-90-R (SCL
      90-R) and family competence as measured by the Beavers Interaction Scales, with
      particular emphasis on how these relationships vary according to gender. Despite
      the common belief that women need relationships more than men, the psychological
      health of men in this study was as strongly related to their perceptions of
      family quality as women's, perhaps even more so. Male and female adolescents
      appeared to experience family interactions quite differently. Implications for
      research and practice are addressed.

PMID- 10934679
TI  - Intimate justice. III: Healing the anguish of abuse and embracing the anguish of
      accountability.
AB  - This article presents an exploratory approach to couples therapy for abuse based
      on intimate justice theory. The article explains "the accountability axiom,"
      which brings the relationship between the anguish of abuse and the anguish of
      accountability into focus. Understanding the accountability axiom can help
      therapists simultaneously engage both the victim of abuse and the abuser by
      creating two therapeutic environments in conjoint therapy--one environment that
      affirms the victim and one that challenges the abuser. The ideas are based on a
      qualitative study conducted by the authors, and the approach is illustrated with
      a clinical case involving psychological abuse.

PMID- 10934680
TI  - Individual and crossover effects of stress on adjustment in medical student
      marriages.
AB  - High-stress individuals may benefit from social support, although their support
      providers may be adversely affected via stress crossover effects. Individual and
      crossover effects of perceived stress within medical student marriages (n = 30)
      were investigated. Perceived spousal support was positively associated with
      individuals' own marital and emotional adjustment, attenuating stress effects.
      With regard to crossover effects, medical students' perceived stress was
      significantly associated with their spouses' emotional adjustment. Further,
      medical students' own emotional adjustment fully mediated this crossover effect.
      Results suggest that the contagion of negative affect may serve as a key
      mechanism through which stress crossover effects operate in marriage.

PMID- 10934681
TI  - Family-of-origin expressiveness: measurement, meaning, and relationship to
      alexithymia.
AB  - The need for research instruments to assess the impact of affective
      expressiveness within the family is evident, yet few appear to be adequately
      designed for this purpose. In this article, we present two studies addressing
      this need. In the first study, the original 40-item Family-of-Origin Scale was
      administered to 416 students to determine those items that constitute the factor
      structure. This instrument was designed to assess perceived levels of health in
      the family of origin but has unsubstantiated construct validity. Results from a
      confirmatory factor analysis indicated that the instrument has one major factor,
      and results from five other studies provide evidence supporting the construct
      validity. Face validity of this 22-item construct indicates that it assesses an
      individual's perceived level of global expressive atmosphere within his or her
      family of origin. In the second study, the new Family-of-Origin Expressive
      Atmosphere Scale and the 20-item Toronto Alexithymia Scale were administered to
      295 students. Students' self-reported expressive atmospheres in their family-of
      origin scores were significantly correlated with the total scores of alexithymia
      and each of the three factors: impaired ability to identify feelings, impaired
      ability to describe feelings, and externally oriented thinking processes. No
      significant gender differences were found.

PMID- 10934682
TI  - Helping HIV-positive persons to negotiate the disclosure process to partners,
      family members, and friends.
AB  - For people who have been diagnosed with a chronic illness, one inevitable issue
      to be addressed is whether and how to share this information with others. For
      persons who are HIV positive, disclosure presents an especially arduous task. The
      purpose of this article is to offer a strategy to assist marriage and family
      therapists in facilitating client disclosure of an HIV-positive status to
      partners, family members, and friends. In addition, suggestions for setting the
      stage for disclosure to occur and recommendations for client follow-up are
      proposed.

PMID- 10934683
TI  - Lack of consensus in supervision.
AB  - This study describes what occurs when trainees and supervisors encounter a lack
      of consensus in supervision. We identified 120 episodes indicating a lack of
      consensus between a supervisor and a trainee during 23 hr of supervision.
      Qualitative analysis of the episodes described 10 supervisor responses,
      characterized as influence and evaluation, and eight trainee responses,
      characterized as cooperation and deference. The pattern of supervisor-trainee
      interaction was characterized by negotiation and collaboration. Supervisors and
      trainees collaborate to produce a presentation of the trainee as a competent
      clinician and a cooperative trainee. Supervisors identify deficiencies and offer
      requests in a subtle manner that appears open to modification, thus cooperating
      with the trainee's competent and cooperative image.

PMID- 10934685
TI  - The implications of client satisfaction feedback for beginning family therapists:
      back to the basics.

PMID- 10934684
TI  - Internship training in marriage and family therapy: a survey of doctoral program
      objectives and implementation.
AB  - This article presents the results of a survey that examined the implementation of
      the Commission on Accreditation for Marriage and Family Therapy Education
      (COAMFTE) internship requirement by accredited doctoral Marriage and Family
      Therapy (MFT) programs. Representatives from each of 10 doctoral MFT programs
      provided responses to questions regarding program objectives for internship
      training. Respondents also provided subjective impressions regarding the
      effectiveness with which established internship goals are accomplished,
      associated benefits and difficulties, and adequacy of the standards. Results
      suggest that although most programs perceive the internship requirement as
      beneficial, many express concern regarding the effects of the internship
      requirement on other aspects of training and in relationship to the overall goals
      for doctoral MFT education. Conclusions and recommendations are offered based on
      the mixed findings.

PMID- 10934686
TI  - Culture and personality: toward an integrated cultural trait psychology.
AB  - Two theoretical perspectives currently dominate research on culture and
      personality, the cross-cultural trait psychology approach, in which the trait
      concept is central, and the cultural psychology approach, in which the trait
      concept is questioned. Here I review theory and research from both perspectives
      and propose that the tenets of cultural psychology, at least in their more
      moderate forms, can be synthesized with the trait psychology approach, resulting
      in an integrated cultural trait psychology perspective.

PMID- 10934687
TI  - Hypochondriacal concerns and the five factor model of personality.
AB  - Using data from two studies (Ns = 205 and 161), this article examines the
      associations between the domains of the five factor model of personality and
      hypochondriacal concerns (HCs). These associations are explored once covariation
      due to other related traits (somatosensory amplification) and comorbidity factors
      (anxiety, depression, and somatic symptom reporting) have been controlled. As
      predicted, emotional stability was associated with most criteria related to HCs
      and agreeableness was negatively associated with the perceived inadequacy of a
      physician's explanation. Conscientiousness was negatively associated with HCs.
      These associations remained after partialing the comorbidity factors and
      somatosensory amplification. The discussion focuses on the particular role of
      agreeableness and conscientiousness in relation to HCs.

PMID- 10934688
TI  - The impostor phenomenon: self-perceptions, reflected appraisals, and
      interpersonal strategies.
AB  - Three studies tested theoretical assumptions regarding the impostor phenomenon.
      In Study 1, participants completed measures of impostorism, rated themselves, and
      indicated how they thought other people regarded them. Contrary to standard
      conceptualizations of impostorism, high impostors were characterized by a
      combination of low self-appraisals and low reflected appraisals. Study 2 was an
      experiment designed to determine whether the behaviors associated with the
      impostor phenomenon are interpersonal strategies. Participants were told that
      they were expected to perform either better or worse than they had previously
      predicted on an upcoming test, then expressed their reactions anonymously or
      publicly. High impostors expressed lower performance expectations than low
      impostors only when their responses were public. When expectations for
      performance were low, participants high in impostorism responded differently
      under public than private conditions. Study 3 examined the possibility that high
      scores on measures of impostorism may reflect two types of impostors--true
      impostors (who believe that others perceive them too positively) and strategic
      impostors (who only claim that they are not as good as other people think). The
      results did not support this distinction; however, evidence for the strategic
      nature of impostorism was again obtained. Although people may experience true
      feelings of impostorism, these studies suggest that the characteristics
      attributed to so-called impostors are partly interpersonal, self-presentational
      behaviors designed to minimize the implications of poor performance.

PMID- 10934689
TI  - Coping-related expectancies and dispositions as prospective predictors of coping
      responses and symptoms.
AB  - We used Rotter's (1954, 1982) social learning theory and Kirsch's (1985, 1999)
      response expectancy extension thereof to clarify distinctions between coping
      related expectancies (beliefs about the outcomes of coping efforts) and coping
      dispositions (tendencies to use particular coping responses), specifically
      focusing on the role of generalized expectancies for negative mood regulation
      (NMR) as a predictor of individual differences in coping and well-being. Two
      studies using structural equation modeling provided support for direct and
      indirect associations between NMR expectancies and symptoms of depression. In
      Study 1 NMR expectancies predicted situational avoidance coping responses and
      symptoms of depression and anxiety, independent of dispositional avoidance coping
      tendencies. In Study 2, NMR expectancies were associated with depressive
      symptoms, concurrently and prospectively, independent of dispositional optimism
      and pessimism. Both studies indicated that NMR expectancies are more strongly
      associated with depressive symptoms than with symptoms of anxiety and physical
      illness. Results underscore the importance of distinguishing between expectancies
      and other personality variables related to coping.

PMID- 10934690
TI  - The influence of rearing order on personality development within two adoption
      cohorts.
AB  - There is an extensive literature on the relationship between birth order and
      psychological traits, but no previous study has investigated the influence of
      ordinal position on personality development within adoptive siblings. Such a
      design is important because it effectively separates the effects of biological
      birth order and rearing order. Here we report data from two adoption cohorts in
      which subjects were biological first-borns reared in various ordinal positions.
      Data were analyzed with reference to Sulloway's (1996) evolutionarily based
      sibling rivalry theory of birth order effects. Between- and within-family
      analyses indicated that rearing order's influence on personality was very weak.
      The only clear difference was for conscientiousness, on which first-reared
      siblings scored higher. We draw possible implications for Sulloway's theory and
      speculate upon an alternative, prenatal biological process that may produce birth
      order differences.

PMID- 10934691
TI  - [Relationship between cardiovascular risk profile and anti-hypertensive drug use.
      GEDEC (Spanish group of cardiovascular studies].
AB  - BACKGROUND: Hypertension guidelines emphasize the selection of antihypertensive
      treatment on the basis of absolute cardiovascular risk. Moreover, compelling and
      possible indications for each antihypertensive drug class are recommended for
      patients with other concomitant conditions. The aim of the present study was to
      analyze the relationship between the cardiovascular risk profile and co-morbid
      conditions on antihypertensive drug class use. METHODS: This is an observational,
      multicenter, cross-sectional study performed in 2,850 essential hypertensive
      patients. Antihypertensive drug treatment has been evaluated on the basis of the
      presence of other cardiovascular risk factors, target organ damage or
      cardiovascular diseases, as well as the absolute cardiovascular risk profile.
      RESULTS: Patients with diabetes were treated more frequently with calcium channel
      blockers (CCB) and ACE inhibitors. However, the presence of hypercholesterolemia
      or smoking habit did not influence the use of antihypertensive drug classes. The
      presence of cerebrovascular disease increased the use of CCB and ACE inhibitors,
      whereas coronary disease increased the use of CCB and betablockers. The use of
      diuretics and angiotensin II receptor antagonists was increased in patients with
      cardiac failure, whereas neither betablockers nor ACE inhibitors were affected by
      this concomitant disease. Patients with the highest cardiovascular risk received
      more antihypertensive treatment than those with lower risk, but this was not
      accompanied by switching from old classes to new ones. CONCLUSION: Cardiovascular
      risk profile seems to have little influence on the use of antihypertensive drug
      classes, particularly the presence of hypercholesterolemia or cardiac failure. It
      seems adequate to emphasize the necessity of an individualization of
      antihypertensive treatment, based on the presence of concomitant conditions that
      influence the absolute cardiovascular risk.

PMID- 10934692
TI  - [Treatment of osteoporosis with calcium and vitamin D. Systematic review].
AB  - BACKGROUND: Systematic review of the efficacy of calcium and vitamin D for the
      treatment of osteoporosis. MATERIAL AND METHOD: Review of the database MEDLINE
      between 1996 and may 1998, by the key words: osteoporosis, calcium, vitamin D
      (and related terms) and randomized clinical trial. Review of the electronic
      versions of Best Evidence, The Cochrane Library, congress abstracts and
      references from two main textbooks. Ascending review of the literature. All the
      reviews were performed independently by two of the authors. Design parameters and
      main results of the primary publications of the identified trials were tabulated.
      Two independent observers carried out methodological scoring of the studies.
      Results were tabulated and a judgement made for the results. RESULTS: Eleven
      studies on calcium, 8 of vitamin D and 12 about calcitriol and other hormone
      derivatives were included. Studies with calcium were mainly performed on non
      clinical populations and in three anti-fracture efficacy was analyzed. Results
      were positive in population with low baseline intake and substantial
      supplementation. Trials on vitamin D were done in non-clinical and on
      institutionalized populations. Trials with calcitriol were developed mainly in
      osteoporotic fracture populations and reached poorer methodological validity
      scores. Heterogeneity of the studies precluded a meta-analysis of the different
      treatments. Studies on calcium showed clinical efficacy in a more consistent way.
      Inter-observer score was good (kappa = 0.81) and there were no significant
      correlations between sample size and effect in the different studies.
      CONCLUSIONS: Calcium treatment is efficacious in populations with low intake
      receiving substantial supplementation. Vitamin D is efficacious associated with
      calcium mainly in deficient populations. Efficacy of calcitriol and other
      derivatives is more controversial.

PMID- 10934693
TI  - [Prevalence of dyslipidemia and its phenotypes in recently diagnosed essential
      arterial hypertension].
AB  - BACKGROUND: To know the prevalence of phenotypic dyslipidemias and their clinical
      and metabolic characteristics in recently diagnosed hypertensive patients.
      METHODS: Consecutive study of 158 essential hypertensive patients without
      previous pharmacological treatment. RESULTS: 69.6% of the patients had some kind
      of dyslipidemia, being the isolated increase of Lp(a) (27.3%) the most prevalent
      and the hyperapobetalipoproteinemia the less (10.0%). Age, sex, smoking, alcohol
      consumption, uric acid, systolic and pulse pressure and serum glucose were
      different among phenotypes. CONCLUSIONS: Essential hypertensive patients have
      high and heterogeneous prevalence of dyslipidemias.

PMID- 10934694
TI  - [Heart and hypertension: joined or separated?].

PMID- 10934695
TI  - [Dyslipidemia and arterial hypertension: association or coincidence?].

PMID- 10934696
TI  - [Langerhans cell histiocytosis. Clinical longitudinal study of 21 patients].
AB  - BACKGROUND: Clinical data of patients with Langerhans cell histiocytosis are well
      established, although new diagnostic methods and specially long term evolution of
      the disease with lung involvement are not well-known. METHODS: In all cases,
      patients were diagnosed by means of pathologic study of the lung samples, either
      by transbronchial biopsy in 7 patients, or by surgical lung biopsy in 8 patients.
      Six patients were diagnosed by bone biopsy. Other patients were diagnosed by
      bronchoalveolar lavage (BAL). In 4 patients, who underwent BAL, the study of
      antibodies CD1 (CD1a) was positive (> 5%). Lymphocytopenia was detected in 28% of
      patients, whereas no decrease in delayed cutaneous hypersensitivity tests was
      detected in any of them. After a follow-up study of 12.8 years (range: 4-22
      years), 7 patients had dead, 6 patients showed severe lung involvement and other
      5 patients did not have lung affection. CONCLUSIONS: The diagnosis of Langerhans
      cell histiocytosis has improved by detection of immunologic and histochemical
      markers recently introduced. The study of the delayed cutaneous hypersensitivity
      tests did not show anergy or hipoergy. Long term evolution of patients with lung
      involvement is poor.

PMID- 10934697
TI  - [Update on breast cancer and pregnancy].

PMID- 10934699
TI  - [Random assignment: needs and limitations].

PMID- 10934698
TI  - [Pharmacodynamics of antibiotics in otitis media].

PMID- 10934701
TI  - [Selection of initial antihypertensive drug treatment in primary health care].

PMID- 10934700
TI  - [Macroglossia and tongue papular injury due to mirtazapine treatment].

PMID- 10934702
TI  - [Medical engineering technologies of diagnosis and correction of higher mental
      functions in children and adolescents].
AB  - This is an introductory article for this issue of the journal prepared on the
      basis of the proceedings of the Scientific-and-Practical Conference on Problems
      in Instrumental Evaluation of Higher Mental Functions and Dysfunctions in
      Children and Adolescents by using computer-aided test systems (medical
      engineering technologies developed at the turn of millennia). The paper deals
      with the analysis of the themes of the conference, its composition, and issues
      examined.

PMID- 10934703
TI  - [Medical engineering computer technologies of testing cognitive functions in
      children].
AB  - Studies of higher mental functions in children are shown to present great
      difficulties in many parameters. Analysis has provided a number of requirements
      for medical devices and complexes and principles of their construction. Based on
      these data, the authors have developed and put computer test systems into
      practice, their advantages being shown. The studies of cognitive functions in
      children by using computer test systems are dealt with.

PMID- 10934704
TI  - [Instrumental means of psychophysiological studies of higher mental functions in
      children and adolescents--from devices and complexes to medical engineering
      technologies of diagnosis, rehabilitation and monitoring].
AB  - The paper outlines new engineering decisions of provision of medical engineering
      technologies of the quantitative assessment of the status and rehabilitation of
      higher mental functions of children and adolescents in health and in diseases.
      The theoretical and experimental rationales for the development of new
      technologies, basic principles and examples of their realization are given.

PMID- 10934705
TI  - [Patho- and neuropsychological monitoring in disorders of psychoneurological
      development by using testing and computer programs].
AB  - The paper outlines the computer-aided testing diagnostic systems used at the
      Moscow Therapeutical Research Center for Prevention and Treatment of Mental and
      Nervous Disability. They are based on the complex factorial approach. This
      approach takes into account the developmental vectors in a child. These include
      motor, perceptive, intellectual, and communicative vectors. The complex approach
      makes it possible not only to establish the actual level of development of basic
      higher mental functions, but to determine treatment-induced developmental changes
      and prognosis.

PMID- 10934706
TI  - [Possibilities of the use of psychophysiological monitoring].
AB  - The paper deals with psychophysiological monitoring on an automatic [symbol: see
      text] phi K-01 psychophysiological diagnosis unit made in Russia. The unit is
      intended to detect latent and initial manifestations of stress reactions in
      healthy individuals and to evaluate the efficiency of psychopharmacological
      therapy and psychotherapy.

PMID- 10934707
TI  - [Use of know-how engineering technologies for psychological diagnosis with the
      aid of personal computers].
AB  - The development of computer versions of psychodiagnostic procedures for
      individualized clinical studies is considered. A number of criteria that may form
      a basis for psychodiagnostic questionnaire procedures and that determine the
      computer interpretation of an examinee's testing results are outlined.

PMID- 10934708
TI  - [Use of computer-assisted stabilography and the method of computer-assisted
      biomechanical study of gait in the diagnosis of posture and motor disorders in
      patients with different forms of infantile cerebral paralysis].
AB  - The paper presents and analyzes the results of assessment of vertical stability
      and walk in patients with infantile cerebral paralysis before and after dynamic
      proprioceptive correction, which is of great importance for differential
      diagnosis of different forms of this disease, for controlling the course of
      therapeutical measures, for working out criteria for the efficiency of treatment.

PMID- 10934709
TI  - [Study of human psychophysiological features during in-depth occupational
      counseling].
AB  - The paper considers a complex of methods used in diagnostic psychophysiological
      studies in consulting practice by using a computer "Psychomat" complex.

PMID- 10934710
TI  - [Computer-assisted screening of the cognitive sphere in school children].
AB  - The cognitive sphere was studied in schoolchildren with good study progress by
      using computer test systems. This provided age-dependent standards of major
      cognitive functions: perception, attention, memory, psychomotor activity, and
      thinking that determine the quality of cognitive activity. Comparatively, this
      may objectify age-specific prognosis of schoolchildren and specify causes of
      learning difficulties in children.

PMID- 10934711
TI  - [Computer technologies in the hygienic studies of children and adolescents].
AB  - Computer technologies were used to develop new hygienic technologies of the
      activities of civil service in providing sanitary and epidemiological well-being
      to the population, to devise methods for evaluating and predicting the influence
      of environmental factors on human health. The specific developmental features of
      the psychophysiological status in schoolchildren were revealed in relation to
      their age, sex, the hygienic schooling and living conditions, which may
      substantiate a package of goal-oriented measures for health promotion and
      preservation in children.

PMID- 10934712
TI  - [Study of functional interhemispheric asymmetry in children in the context of
      electrophysiological markers and the efficiency of neurological rehabilitation].
AB  - The paper presents neurological findings of children and adolescents, which
      included the determination of the individual profile of cerebral asymmetry by 3
      spheres: motor, sensory, and mental, as well as electrophysiological measurement.
      To develop biology teaching methods by taking into account the individual profile
      of pupils' brain asymmetry is an aim of this study.

PMID- 10934713
TI  - [Correlations between mental maturity and higher mental function in preschool
      children].
AB  - This communication presents the results of comparative study of 23 quantitative
      characteristics of the mental development of a child (the data of
      neuropsychological diagnosis of higher cortical functions by the procedure
      developed by I. F. Markovskaya, 1993) and 112 parameters of higher mental
      functions (perception, memory, assimilation and reproduction of rhythmic stimuli,
      behavioral strategy in the determined environment) recorded by a complex of
      microprocessor psychophysiological apparatuses, such as "Rhythmotest",
      "Mnemotest", and "Binatest".

PMID- 10934714
TI  - [Problems of special education of handicapped children in the Russian
      Federation].
AB  - The problems in the control of health, its promotion, and specialized education
      in handicapped children in Russia are considered. Examples of improving the
      differential network of specialized (correcting) educational establishments and
      data on other measures aimed at solving the above problems are given.

PMID- 10934715
TI  - [Endovascular surgery of cerebral aneurysm].

PMID- 10934717
TI  - [Percutaneous transluminal angioplasty].

PMID- 10934716
TI  - [Recent advances in AVM embolization].

PMID- 10934718
TI  - [Neuroendovascular treatment for acute thrombotic stroke].

PMID- 10934719
TI  - [Periventricular leukomalacia: etiology, pathology and plasticity].

PMID- 10934720
TI  - [Long-term results of gamma radiosurgery].

PMID- 10934721
TI  - [Comparison of myelin-forming cells as candidates for therapeutic transplantation
      in demyelinated CNS axons].
AB  - Demyelination of axons resulted in distinct reduction of conduction velocity or
      block of conduction. Remyelination by transplantation of myelin-forming cells may
      provide a therapeutic approach for demyelinated diseases. However, which cell
      type will be the most appropriate candidate for such a cell therapy is not
      established. To investigate how effective grafted neonatal brain cell (BC)
      (including oligodendrocyte and astrocyte) isolated from neonatal fronto-temporal
      lobes, adult olfactory ensheathing cell (OEC) or adult Schwann cell (SC) may be
      for demyelinated CNS axons in vivo, dorsal columns(DCs) of adult rat spinal cord
      were demyelinated at Th 11 by X-ray irradiation (day 0) and the injection of
      ethidium bromide (day 3), and transplanted 5 x 10(4) of BCs, 3 x 10(4) of OECs,
      or 3 x 10(4) of SCs into the lesion (day 6). Day 28-31, spinal cord were removed
      and transferred an in vitro recording chamber to record field potentials using
      glass micropipettes, to investigate conduction properties at 36 degrees. Normal
      DCs were recorded in same manner. Histological examination revealed that OECs and
      SCs resulted in substantial SC-like patterns of remyelination to equal degree, BC
      transplantation resulted in less myelination. The conduction velocities were
      significantly improved to 4.2 +/- 2.4 m/s(BC, n = 5), 8.5 +/- 3.3 m/s(OEC, n = 6)
      and 7.7 +/- 1.5 m/s(SC, n = 5), compared to demyelinated axons(1.2 +/- 0.4 m/s, n
      = 7). A 600 Hz 0.5 sec stimulus train led to an amplitude decrement of 7.1 +/-
      7.5% (n = 7) in demyelinated axons. Following transplantation, the amplitude
      decreased in 31.3 +/- 18.7% (BC, n = 5), 49.9 +/- 19.9% (OEC, n = 6) and 66.2 +/-
      11.9% (SC, n = 5). Transplanted OECs and SCs enhanced the remyelination of
      demyelinated CNS axons, and improved conduction properties were similar, and more
      effective than that induced from isolated CNS tissue which included
      oligodendrocyte.

PMID- 10934722
TI  - [A case with symptomatic epilepsy and mirror movement due to unilateral
      schizencephaly].
AB  - Schizencephaly is an extremely rare congenital disease caused by abnormal
      neuronal migration. The etiology of schizencephaly is not established but
      vascular disturbance in early childhood could cause this condition. We have cared
      of a patient with schizencephaly. The patient was 47 year old male. He had focal
      motor seizure with secondary generalization. Neurological examination revealed,
      mild left hemiparesis, left pyramidal signs with no sensory impairment, left
      hemiatrophy, and mirror movement. MRI findings showed schizencephaly, open lip
      type(type II) in right cerebral hemisphere. His epileptic seizure was controlled
      by administration of sodium valproate. The possible mechanism of this mirror
      movement in his left hand and leg could be reorganization of non-affected brain
      and disinhibition on homolateral pyramidal tract in non-affected left cerebral
      hemisphere by the transcallosal inhibitory pathyway from affected right cerebral
      hemisphere. Sodium valpronate can not suppress this mirror movement.

PMID- 10934723
TI  - [A case of symmetrical aneurysms at the bilateral middle cerebral arteries
      associated with the deep seated arteriovenous malformation in the midline].
AB  - A case of symmetrical aneurysms at the bilateral middle cerebral arteries (MCA)
      associated with the deep seated arteriovenous malformation (AVM) in the midline
      was presented. Because symmetrical aneurysms at the MCA are 1.17% of all
      aneurysms, and those associated with the deep seated AVM in the midline are very
      rare. A 75-year-old female suffered from a sudden onset of a severe headache and
      a loss of consciousness, and was admitted to our department on June 14, 1996.
      Computed tomography(CT) showed a subarachnoid hemorrhage (SAH) in the right
      sylvian fissure (Fisher's Group 4). Bilateral symmetrical MCA's aneurysms and the
      deep seated AVM were clarified by angiography. The symmetrical aneurysms stood
      out anterior lateral side and the right aneurysm had bleb. On the other hand, the
      afferent vessels of the AVM were the branches of bilateral posterior cerebral
      arteries, and the efferent vessel was the vein of Galen. So we determined SAH due
      to right MCA aneurysm, and performed the neck clipping of the ruptured aneurysm.
      The symmetrical aneurysms at the MCA associated with AVM in midline have not been
      reported. Each parent's artery was not connected each other. These origins,
      therefore, are suggested to be related not only to acquired factors like
      hypertension, hemodynamic stress etc, but also to a congenital factor. The origin
      of the saccular aneurysm is suggested congenital either but it isn't definite.

PMID- 10934724
TI  - [Intrasellar epidermoid cyst].
AB  - We report a rare case of intrasellar epidermoid cyst. A 61-year-old man presented
      with complaints of the disturbance of consciousness and general fatigability. His
      laboratory data showed panhypopituitarism and MRI revealed the cystic tumor
      located at the intrasellar region. Tumor was removed by transsphenoidal approach
      and histological examination of the surgical specimen showed that the cyst wall
      was composed of the stratified squamous epithelium with keratohyaline granules.

PMID- 10934725
TI  - [Homocystinuria with generalized chorea and other movement disorders: a case
      report].
AB  - We report a 50-year-old right-handed woman who, at age 20, was diagnosed to have
      homocystinuria presumably due to cystathionine beta-synthase deficiency. At age
      40 years, involuntary movements developed insidiously, affecting her face, neck
      and upper limbs. During the next 10 years, involuntary movements progressed and
      she could no longer walk. Examination disclosed bilateral lens dislocation and
      marfanoid skeletal deformity. Muscle strength was mildly decreased in the right
      arm and bilateral legs. There was hyperreflexia in the right upper and bilateral
      lower extremities without Babinski sign. Muscle tone was mildly increased in the
      neck and bilateral upper extremities. She had persistent generalized choreic
      movements, dystonia affecting the face and neck, and resting and postural tremor
      in the upper limbs and tongue. A cranial CT scan showed an old low density lesion
      in the left frontal area. Involuntary movements in homocystinuria is rare and, to
      our knowledge, only 9 cases have been reported. This case was unique in that
      involuntary movements developed in the adulthood.

PMID- 10934727
TI  - [Splenial malignant lymphoma].

PMID- 10934726
TI  - [A case of Marchiafava-Bignami disease demonstrated by MR diffusion-weighted
      image].
AB  - A Case of Marchiafava-Bignami disease demonstrated by MR diffusion-weighted image
      (DWI) was reported. A 55-year-old male with chronic alcoholism demonstrated
      dysarthria, disorientation and apraxia of left-hand. Sagittal view on MRI showed
      a swelling of the corpus callosum. The body and splenium of the corpus callosum
      showed symmetrically iso-intensity in T1 WI and hyperintensity in T2 WI, and
      remarkable hyperintensity in fluid attenuated inversion recovery images. DWI
      showed a definite hyperintensity area on the corpus callosum and the apparent
      diffusion coefficient (ADC) map presented the decreased water self-diffusion.
      These findings differed from the other demyelinating diseases, such as multiple
      sclerosis. We considered these DWI findings were the initial changes on MBD which
      preceded the demyelination. To our knowledge, this is the first report of DWI
      that was used in a case of Marchiafava-Bignami disease.

PMID- 10934728
TI  - [A 67-year-old man with progressive disturbance of gait].
AB  - We report a 67-year-old man with progressive disturbance of gait. He was well
      until the spring of 1993 (62 years of the age), when he noted an onset of
      unsteady gait. He also noted that he started to have a difficulty in playing
      tennis, in which he became unable to hit the ball with his racket. He also noted
      parkinsonian features such as bradykinesia and loss of hand dexterity. He was
      treated with levodopa, which did not improve his symptoms. His MRI revealed
      marked atrophy of the cerebellum and the pons. The criss-cross high signal lesion
      was seen in the center of the pons. The third ventricle was dilated. The putamen
      was unremarkable. His subsequent course was complicated by easy to fall,
      difficulty in swallowing with episodes of aspiration pneumonia. He also developed
      nocturnal apneustic episodes. He was admitted to our hospital on November 15,
      1998, when he was 67 years of the age. He had low grade fever and low blood
      pressure (98/70). He was anemic but not icteric. Tumors were palpated in his jaw,
      anterior chest, and in the left arm. He was alert but unable to convey his desire
      because of dyspnea and tracheostomy. His gaze was slightly restricted in the
      horizontal direction and markedly so in the vertical direction. Motor functions
      were difficult to evaluate. His clinical course was complicated by atelectasis of
      the right lung and pleural effusion. He developed marked edema and oliguria. He
      developed sudden bradycardia and expired on December 26, 1998. He was discussed
      in a neurological CPC and the chief discussant arrived at the conclusion that the
      patient had multiple system atrophy. Majority of the audience agreed with this
      diagnosis. Post-mortem examination revealed a lung cancer in the right lung
      (undifferentiated adenocarcinoma) with metastases to the liver, kidneys, lymph
      nodes, pericardium, pleura, skin, bone marrow, and the brain. Neuropathologic
      examination revealed marked atrophy of the pons and the cerebellum. The putamen
      showed brownish discoloration and atrophic changes. The substantia nigra showed
      marked neuronal loss and gliosis. Oligodendrocytic inclusion bodies (alpha
      synuclein positive) were seen in the putamen, globus pallidus, substantia nigra,
      pontine nucleus, cerebellar white matter, internal capsule, cerebral peduncle,
      and the spinal cord. These findings are consistent with the pathologic diagnosis
      of multiple system atrophy. What was interesting to us was the presence of
      neurofibrillary tangles in the substantia nigra, nucleus ruber, globus pallidus,
      and subthalamic nucleus. Tuft-shaped astrocytes were also seen. This patient
      appears to be a rare example of combination of MSA and PSP.

PMID- 10934729
TI  - Influence of peroxide impurities in povidone and crospovidone on the stability of
      raloxifene hydrochloride in tablets: identification and control of an oxidative
      degradation product.
AB  - The purpose of this study was to identify a degradation product in a tablet
      formulation of raloxifene hydrochloride (R-HCl), delineate the role of excipients
      in its formation, and develop a rational strategy for its control. The degradant
      was identified as an N-oxide derivative of the drug substance based upon
      spectroscopic characterization and chromatographic comparison to the synthetic N
      oxide. To identify the factors contributing to the formation of N-oxide, binary
      mixtures of each excipient with R-HCl were exposed to 125 degrees C in open
      containers. Raloxifene hydrochloride underwent an order of magnitude increase in
      conversion to the N-oxide in the presence of two excipients, povidone and
      crospovidone, as compared with its conversion in the presence of other
      excipients. To confirm a hypothesis that peroxide impurities in these two
      excipients contributed to the oxidation of the drug substance, tablet lots were
      spiked with quantities of H2O2 equivalent to 200, 400, 600, and 800 ppm peroxide
      over the intrinsic levels present in povidone and crospovidone. A strong
      correlation was observed between the total peroxide level and the quantity of the
      N-oxide formed upon accelerated storage. From these experiments a rational limit
      test for peroxide content in povidone and crospovidone was adopted as part of a
      control strategy to limit formation of the degradation product.

PMID- 10934730
TI  - The prediction of variability occurring in fluidized bed coating equipment. I.
      The measurement of particle circulation rates in a bottom-spray fluidized bed
      coater.
AB  - The purpose of this work was to investigate the effect that changes in design and
      process variables had on the movement of particles around a fluidized bed coating
      apparatus. To measure the mean and variance of the particle cycle time
      distribution (CTD), the number of passages taken by a magnetic tracer particle
      through the spray zone was measured by a detector coil wound around the
      partition. The reproducibility of the measurement technique was tested by taking
      repeated measurements of the tracer particle movement, using similar bed
      operating conditions, and the method was found to give reproducible results. A
      series of experiments was carried out by varying operating conditions such as the
      partition gap, fluidizing air rate, and partition diameter and length, and
      measuring the change in the rate at which the tracer particle circulated in the
      coating device. The results of the experiments showed that, over the range of
      parameters tested in this work, the partition gap had the strongest influence on
      the rate of particle circulation. Moreover, for the 6-in.-diameter Wurster
      process used in the current work, the mean circulation time for the 1.1-mm
      diameter Nu-Pareil particles was found to vary over the range of 2.2-10.4 sec. In
      addition, the mean and standard deviation of the CTD could be linearly correlated
      over a wide range of operating conditions, with a correlation coefficient of
      0.80. Finally, an estimate of the variability in mass coating uniformity was made
      based on the results from the cycle time distributions. It was concluded that the
      effect of variability in the CTD could account for only a small fraction of the
      variability in the observed mass coating distribution.

PMID- 10934731
TI  - The prediction of variability occurring in fluidized bed coating equipment. II.
      The role of nonuniform particle coverage as particles pass through the spray
      zone.
AB  - The purpose of this work was to evaluate the relative importance of particle
      circulation and particle-to-particle mass coating distribution on the overall
      mass coating distribution obtained in a Wurster process. A series of batch
      coating experiments was carried out over a range of operating conditions, in
      order to evaluate the particle-to-particle variation in the mass distribution of
      coating material deposited during batch coating operations. Results showed that
      the major component of variance was due to the variation in the amount of coating
      received per particle per pass through the spray zone. The variation in the
      number of times a particle passed through the spray zone was considerably less
      important. Two models were developed to explain the results of the experimental
      program. The first model categorized particles moving through the spray zone as
      either receiving coating or not. Thus, the distribution of coating material per
      particle per pass is described by a Bernoulli probability distribution. Using
      this picture of the spray process, the number of particles receiving coating
      during any given pass through the spray zone was found to vary between 2 and 6%.
      A second model was developed to explain the major cause of variation. This model
      explains the variation in terms of the hindering or sheltering effect that
      particles close to the source of the spray have on particles farther away.
      Although the agreement of model predictions with experimental results is only
      fair, it is believed that this model captures the main cause of particle-to
      particle variation occurring in batch coating operations and thus is the first
      model to explain this phenomenon.

PMID- 10934732
TI  - Development and testing of an improved parenteral formulation of phenytoin using
      2-hydroxypropyl-beta-cyclodextrin.
AB  - The objective of this study was to increase the solubility of phenytoin by
      complexing it with varying concentrations of 2-hydroxypropyl-beta-cyclodextrin
      (HPBCD) and create an entirely aqueous formulation with a pH significantly closer
      to physiologic pH (7.4). The phenytoin-HPBCD complexation was characterized using
      phase-solubility analysis at HPBCD concentrations ranging from 10 to 50% w/v over
      the pH range of 7.4-11.0. The two most promising formulations, i.e., a
      formulation consisting of 40% HPBCD at pH 10.4, and a second formulation
      consisting of 20% HPBCD at pH 11.0, were selected for further study. Both
      formulations were entirely aqueous and had a significantly decreased pH compared
      to the original commercial formulation (Parke-Davis, pH 12.0). These formulations
      also exhibited a significantly decreased tendency to precipitate in vitro. The
      tissue irritation potential of the 20% w/v HPBCD formulation at pH 11.0 was found
      to be reduced considerably compared to the commercial injection in a BALB/c mouse
      model.

PMID- 10934734
TI  - Formulation and evaluation of vinylpyrrolidone/vinylacetate copolymer
      microspheres with carbamazepine.
AB  - Vinylpyrrolidone/vinylacetate copolymer (VP/VAc) was used for the enhancement of
      dissolution rate of carbamazepine, an antiepileptic drug characterized by very
      low water solubility. Microspheres containing different drug-to-polymer ratios
      were prepared using a solvent-evaporation technique and their physical
      characterizations were carried out by differential scanning calorimetry, x-ray
      diffractometry, and scanning electron microscopy. Through the solubilization
      kinetics and dissolution rates studies, the in vitro drug availability of the
      microspheres was evaluated. These results showed that the dissolution of
      carbamazepine in gastrointestinal fluids from all of the prepared formulations
      was increased with respect to the drug itself. However, the best dissolution
      parameters were obtained from 1:10 w/w system because of the presence of the drug
      in amorphous form and its efficient encapsulation.

PMID- 10934733
TI  - Evaluation of high molecular weight poly(oxyethylene) (Polyox) polymer: studies
      of flow properties and release rates of furosemide and captopril from controlled
      release hard gelatin capsules.
AB  - The powder characteristics and the effect of the molecular weight of polymers as
      diluents on the release rate of furosemide and captopril from hard gelatin
      capsules were evaluated. The high molecular weight polymers studied were
      poly(oxyethylene) homopolymers (Polyox), with molecular weight ranging from
      4,000,000 to 7,000,000. Powder characteristics suggested good flowability for
      these materials and predicted capsule fill weight uniformity. Swelling
      experiments showed a very high degree of swelling for these materials in both
      gastric and buffer solution. These polymers can sustain the release rate of both
      water-soluble and insoluble drugs from drug delivery systems. The low molecular
      weight polymers have a less pronounced sustained-release effect compared to the
      high molecular weight polymer material (i.e., those with 7,000,000 molecular
      weight). An increase in the content of polymer results in a decrease in the
      release rate of the drug. The solubility of the drugs clearly influenced the
      release rate. Release kinetics were evaluated and appeared to be influenced by
      the molecular weight of the polymer, the solubility of drug, and the ratio of the
      drug to polymer in the capsule. Bimodal release kinetics were exhibited by a
      number of furosemide formulations (i.e., F5 and F8).

PMID- 10934735
TI  - Temperature- and moisture-induced crystallization of amorphous lactose in
      composite particles with sodium alginate prepared by spray-drying.
AB  - The purpose of this study was to investigate the temperature- and moisture
      induced crystallization of amorphous lactose in the composite particles prepared
      by spray-drying an aqueous solution of crystalline lactose and sodium alginate.
      The temperature-induced crystallization of amorphous lactose in the composite
      particles was suppressed by increasing the amount of sodium alginate in the
      particles. The stabilizing effect of sodium alginate on amorphous lactose in the
      composite particles was greater than that in physical mixtures having the same
      formulating ratios. The improved stability of amorphous lactose in the composite
      particles was attributed to an increase in the glass transition temperature (Tg)
      of the mixture. Moisture-induced crystallization of amorphous lactose was also
      retarded by increasing the amount of sodium alginate in composite particles.
      Although the Tg of the mixture was reduced by increasing the water content of the
      particles, the values were higher than that of 100% amorphous lactose when
      particles of the same water content were compared. The change in the Tg of the
      composite particles with increasing water content was interpreted as involving
      three components of the Gordon-Taylor equation. In the amorphous lactose-sodium
      alginate systems, the Tg values of the composite particles containing sodium
      alginate were higher than the theoretical line predicted by two components of the
      Gordon-Taylor equation. These results suggested that there was a specific
      interaction between the sodium alginate and lactose molecules. This specific
      interaction was suggested by the fact that only very little amorphous lactose was
      measured in the spray-dried composite particles stored under humid conditions
      using differential scanning calorimetry. This molecular interaction may also be
      partly responsible for the suppression of both the temperature- and moisture
      induced crystallization of amorphous lactose in the composite particles.

PMID- 10934736
TI  - Scaleup of a high-shear granulation process using a normalized impeller work
      parameter.
AB  - A method was evaluated to accurately identify the granulation end points of
      microcrystalline cellulose formulations by monitoring impeller work during high
      shear processing. Impeller watt meters were calibrated in situ to a common
      standard to enable direct comparison of power values between equipment.
      Integration of the impeller power (watts) versus time (seconds) profile provides
      an energy parameter (watt seconds) or "work of granulation" for correlation with
      physical changes in tablet properties and performance. Granulation end points
      were accurately predicted for 25-, 65-, and 150-liter manufacturing scales on the
      basis of development work run on 5.0- and 10-liter equipment using work values
      normalized for the weight of dry powders in the granulator (watt sec/g). The
      ability to arrive at functionally equivalent granulation end points, in different
      equipment and at different impeller speeds, was established through comparison of
      cohesion indexes (slopes of the tablet breaking strength versus compression force
      profiles) and granulation size distributions determined by sieve analysis. Work
      measured at the impeller correlated quantitatively with changes in the
      granulation bulk and tapped densities, average particle size of the finished
      powders, and cohesion index, independent of granulator make or model. The
      observed changes in granulation properties, however, did not correlate with
      individual process variables such as impeller power (watts) or process time.

PMID- 10934737
TI  - Modulation of drug release rate of diltiazem-HCl from hydrogel matrices of
      succinic acid-treated ispaghula husk.
AB  - The feasibility of using succinic acid-treated ispaghula husk in matrix-based
      tablets of diltiazem-HCl was investigated. The sample prepared using 4:1 weight
      ratio of ispaghula husk to succinic acid showed improved swelling and gelling. A
      3(2) factorial design was employed to investigate the effect of amount of
      succinic acid-treated ispaghula husk and dicalcium phosphate (DCP) on the
      percentage of the drug dissolved in 60, 300, and 480 min from the compressed
      tablets. The results of multiple linear regression analysis revealed that the
      significance of the amount of succinic acid-treated ispaghula husk was greater in
      magnitude than that of the amount of DCP in controlling the drug release.
      Acceptable batches were identified from a contour plot with constraints on the
      percentage drug released at the three sampling times. A mathematical model was
      also evolved to describe the entire dissolution profile. The results of F-test
      revealed that the Higuchi model fits well to the in vitro dissolution data. The
      tablets showed considerable radial and axial swelling in distilled water.
      Succinic acid-treated ispaghula husk can be used as an economical hydrophilic
      matrixing agent.

PMID- 10934738
TI  - Drug release from film-coated chlorpheniramine maleate nonpareil beads: effect of
      water-soluble polymer, coating level, and soluble core material.
AB  - The purpose of this research was to use a new drug release model to study the
      effects of formulation parameters on drug release from a film-coated
      chlorpheniramine (CPM) nonpareil system. The film-coated CPM nonpareils were
      prepared by using a fluid bed apparatus. A hydroxylpropylmethylcellulose (HPMC)
      solution was blended with an aqueous ethylcellulose dispersion (Surelease) to
      adjust the permeability of the film. The apparent permeability of samples was
      obtained from dissolution data using a previously reported drug release equation.
      The apparent permeability was plotted versus the film coating level or the HPMC
      concentration in the film. When the natural logarithm of the apparent
      permeability versus coating level was graphed, a biphasic plot was observed in
      the group without HPMC in the film, showing the occurrence of a critical coating
      level. It was suggested that a mechanically formed porous film (due to an
      incomplete coating) could change to a nonporous film after the bead was
      completely coated. However, in the group that contained 12% HPMC in the film, the
      critical coating level was not observed. A porous film, formed by the leaching
      out of the water-soluble polymer, would not change to a nonporous film even after
      the bead is completely coated. Through a mathematical derivation, the decrease of
      apparent permeability versus coating level was related to the reduction of the
      total hole area. The apparent permeability was found to increase with the HPMC
      concentration. After a critical concentration was reached, the further addition
      of HPMC into the film caused a rapid increase in apparent permeability. The
      critical HPMC concentration was related to a minimum domain formation
      concentration (MDFC). A rapid increase of the drug release was observed when the
      dissolution profile of a sample made from a regular sugar nonpareil core
      (soluble) was compared with the sample made from a precoated nonpareil core
      (insoluble), which suggests that the drug release can be enhanced by the
      dissolution of the core. A minimum concentration of the HPMC was required to
      effectively modify permeability of the film. The critical coating level and
      critical concentration of HPMC can be determined from the apparent permeability
      plot using a previously published equation. The dissolution of a soluble core can
      greatly enhance the release of the drug from the nonpareil system.

PMID- 10934739
TI  - In situ gel formulations for gene delivery: release and myotoxicity studies.
AB  - The in vitro release of plasmid DNA and salmon sperm DNA from in situ gel
      formulations was investigated. Two in situ gel systems were studied: (a) an
      interpolymeric complex (IPC) of water-soluble polymers polymethacrylic acid (PMA)
      and polyethylene glycol (PEG) and (b) a hydroxypropylmethylcellulose-carbopol
      system (H:C). Two-way analysis of variance with replication demonstrated that
      both gel composition and medium pH influenced significantly the release of
      plasmid DNA from in situ gel formulations. When the release of both types of DNA
      was compared, higher release was observed for plasmid DNA compared to genomic
      salmon sperm DNA. Conformational analysis of the released plasmid DNA showed that
      DNA was released without degradation, but with remarkable conversion from
      supercoiled (SC) to open circular (OC). In addition, the tested in situ gel
      systems demonstrated protection from DNAse I degradation. The myotoxicity of the
      injectable gelling solutions was assessed by the cumulative release of creatine
      kinase (CK) over 120 min from the isolated rodent extensor digitorum longus (EDL)
      muscle. A higher level of cumulative CK was observed for IPC when compared to H:C
      (2:1). These results demonstrate that the in situ gelling systems can be
      considered as a valuable injectable controlled-delivery system for pDNA in their
      role to provide protection from DNAse degradation.

PMID- 10934740
TI  - Improvement of solubility and oral bioavailability of rutin by complexation with
      2-hydroxypropyl-beta-cyclodextrin.
AB  - The object of this study was to enhance the solubility, dissolution rate, and
      oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta
      cyclodextrin (HP-beta-CyD). The interaction of rutin with cyclodextrins (CyDs)
      was evaluated by the solubility, and ultraviolet (UV) and circular dichroism (CD)
      spectrophotometries. The chemical and enzymatic stability of rutin was examined
      in an alkaline buffer solution and in rat small intestinal homogenates,
      respectively. Dissolution rates of rutin and its CyD complexes were measured by
      the dispersed amount method. In vivo absorption studies of rutin after oral
      administration via conventional tablet containing rutin alone or its beta-CyD
      complexes was performed on beagle dogs. The stability constants calculated from
      the phase solubility method increased in the order of HP-gamma-CyD < G2-beta-CyD
      < beta-CyD < HP-beta-CyD. Spectroscopic studies also revealed that HP-beta-CyD
      and beta-CyD formed a relatively more stable inclusion complex with rutin. The
      dissolution rates of rutin increased by the complexation with CyDs in the order
      of rutin alone < HP-beta-CyD < or = beta-CyD. HP-beta-CyD inhibited the
      hydrolysis of rutin in the alkaline buffer solution and the small intestinal
      homogenates of rats, suggesting that HP-beta-CyD may stabilize rutin in a
      gastrointestinal tract after oral administration. When the tablet containing
      rutin or its beta-CyD complexes was administered to beagle dogs, the plasma
      levels of homovanillic acid (HVA) (a major stable metabolite of rutin) after oral
      administration of HP-beta-CyD complex were much higher than in either that of
      rutin alone or in its beta-CyD complex. The in vivo absorption study suggests
      that HP-beta-CyD increased the oral bioavailability of rutin from the
      gastrointestinal tracts of beagle dogs because of the increase in solubility,
      faster dissolution rate, and gastrointestinal stability. HP-beta-CyD has a
      significant advantage with respect to providing high aqueous solubility while
      maintaining a lack of toxicity in oral pharmaceutical preparations of rutin.

PMID- 10934742
TI  - Stability of luteinizing hormone releasing hormone: effects of pH, temperature,
      pig skin, and enzyme inhibitors.
AB  - The purpose of this investigation was to determine the stability of luteinizing
      hormone releasing hormone (LHRH) as a function of solution pH, temperature, and
      pig skin with and without enzyme inhibitors. LHRH, incubated with a 0.1 M
      phosphate buffer (pH 2.5-8.1), pig skin, and pig skin with enzyme inhibitors, was
      analyzed using reversed-phase high performance liquid chromatography. The
      solution's pH affected the rate constants of LHRH, following apparent first-order
      kinetics. Maximum stability was achieved at pH 6.05. Therefore, the effect of
      various temperatures (i.e., 65, 75, 80, and 90 degrees C) was studied on the
      stability of LHRH at pH 6.05. The activation energy for the overall reaction was
      23.4 kcal/mol at pH 6.05. The shelf-life of LHRH at 25 degrees C and pH 6.05,
      calculated using the Arrhenius equation, was approximately 4 years. The rate
      constant of LHRH in the skin (area: 9 cm2; thickness: 0.5 mm) was 0.167 hr-1. Out
      of three inhibitors (i.e., aprotinin, bestatin, and leupeptin), bestatin had the
      best stabilizing effect on the degradation of LHRH by the skin. The rate constant
      of LHRH in the presence of bestatin was 0.082 hr-1. Sixty percent of LHRH was
      found to be degraded in the skin within 5 hr in the absence of enzyme inhibitors,
      whereas only 33% of LHRH was degraded in the presence of bestatin (an
      aminopeptidase inhibitor).

PMID- 10934741
TI  - Permeability of chemical delivery systems across rabbit corneal (SIRC) cell line
      and isolated corneas: a comparative study.
AB  - The purpose of this study was to investigate the corneal permeability of
      phenylephrone chemical delivery systems (CDS) across isolated cornea and to
      evaluate the utility of the SIRC cell line (epithelial cells originating from
      rabbit cornea) as an in vitro model for predicting the ocular permeability. The
      effect of benzalkonium chloride (BAC) on the drug permeability through SIRC cell
      layers was also studied. The transport of phenylephrone CDS across the isolated
      cornea of the albino rabbit was measured at various pH values using a two-chamber
      glass diffusion cell, and the results were compared with the reported
      permeability values across SIRC cells of rabbit origin. Corneal membranes showed
      lower flux values for compounds, especially for hydrophilic compounds, than the
      SIRC cell line. A significant correlation was observed between the permeability
      coefficients through corneal membranes and SIRC cells. When the pH of the
      transport medium was increased, the permeability coefficients increased and lag
      times decreased in both in vitro models. Furthermore, both in vitro models showed
      significant correlation between permeability coefficients and lipophilicities of
      the drugs. The three esters, having higher lipophilic characteristics, showed
      higher permeability than phenylephrine HCl. The phenylacetyl ester of
      phenylephrone showed a three-fold increase in penetration across SIRC cell layers
      in the presence of 0.01% BAC. These results suggest that the use of SIRC cell
      layers can reasonably predict the permeability of ophthalmic drugs across corneal
      membranes.

PMID- 10934743
TI  - Communicating tabular data using ORACLE.

PMID- 10934744
TI  - Applying image analysis in the observation of recrystallization of amorphous
      cefadroxil.

PMID- 10934745
TI  - Characteristics of patient and staff victims of assaults in community residences
      by previously nonviolent psychiatric inpatients.
AB  - There currently exists a large body of empirical research examining patient
      assaults in inpatient psychiatric facilities. These studies have focused
      primarily on staff and have found younger, male mental health workers with lower
      levels of formal education and experience as well as nurses involved in restraint
      procedures to be most at risk. However, despite the increased utilization of
      community-based services, little attention has been directed toward patient
      assaults on patients and staff in community settings, particularly residential
      services. This study began to respond to this need by examining patient assaults
      toward other patients and staff in community residences during the first twelve
      months post-discharge for a group of newly discharged patients who were not
      violent as inpatients. This study found female patients and staff to be at
      greater risk for assault than male patients. Lack of experience by staff was also
      a risk factor. The clinical, administrative, and research implications of these
      findings are discussed.

PMID- 10934746
TI  - Disaster psychiatry: principles and practice.
AB  - Increasingly, trauma and disasters are part of everyday life. Psychiatrists can
      play an important role in assisting individuals and communities to recover. They
      bring a unique set of skills and experiences that can be invaluable in minimizing
      morbidity and facilitating recovery. This paper discusses psychological,
      physiological, behavioral, and community responses encountered in the aftermath
      of a disaster. A preventive medicine model of understanding disaster response is
      discussed in which the psychiatrist delineates traumatic stressors and high-risk
      populations. The importance of psychiatric participation in disaster preparedness
      is emphasized. Psychiatric interventions targeted at the various longitudinal
      phases of disaster response are reviewed.

PMID- 10934747
TI  - Children, adolescents and trauma.
AB  - This paper presents an overview of the psychological effects of trauma on
      children and adolescents with specific attention to the epidemiology of traumatic
      experiences, risk factors, developmental effects, the types of traumatic
      experiences albeit a single event trauma or a chronic process trauma, the
      spectrum of clinical presentations, psychiatric and psychological comorbidities
      as well as assessment and therapeutic principles. In addition to the child's
      psychological response to the traumatic stressor communities are often devastated
      by natural or man made disasters. The interactions between the child's response
      with the family and community response as well as community interventions are
      discussed.

PMID- 10934748
TI  - Psychiatric issues in medical-surgical disaster casualties: a consultation
      liaison approach.
AB  - Psychiatrists can increase the efficacy of their response to disaster victims in
      the immediate aftermath of a disaster if they utilize a consultation-liaison
      approach to assessment and management of casualties. Medical-surgical disaster
      responders use an algorithmic, stepwise approach to assess disaster or trauma
      victims. This approach ensures that patients with life-threatening injuries who
      are not expectant are treated first. Then, secondary physical assessments ensure
      proper triage of other victims so that disaster response resources are used most
      wisely. A tertiary psychiatric assessment can assist with differential diagnosis
      of post-disaster neuropsychiatric symptoms and signs to ensure valuable medical
      surgical resources are targeted to the correct patients. Psychiatric triage can
      also identify those victims most in need of early preventive and therapeutic
      psychiatric intervention.

PMID- 10934749
TI  - Debriefing following trauma.
AB  - In this paper we address three areas. First we review the literature on clinical
      intervention using debriefing, second we examine who attends debriefings by
      looking at a study of the 1989 plane crash at Ramstein, Germany and lastly we
      examine the effect of natural debriefing, i.e., talking to family and friends on
      psychiatric outcome in disaster workers by looking at a study of the Sioux City,
      Iowa United plane crash, 1989. Our data suggest that those with high exposure and
      females were more likely to attend a debriefing. People most likely to talk about
      the disaster with spouse/significant other, coworker and/or another person were:
      those with acute PTSD, higher total and intrusive Impact of Event symptoms,
      older, married, those with higher levels of education and higher levels of
      disaster exposure. Better understanding of who attends formal debriefings will
      help identify potential high-risk groups. Similarly, whether talking about the
      disaster is associated with fewer or greater psychological symptoms is important
      to understanding the outcome, mechanisms, and risks of debriefing.

PMID- 10934751
TI  - [CREST syndrome; a changing clinical significance]

PMID- 10934752
TI  - [Arterial stenting and balloon angioplasty in renal artery stenosis] [In Process
      Citation]

PMID- 10934753
TI  - [Phosphate as another major regulator of parathyroid function] [In Process
      Citation]

PMID- 10934750
TI  - Biological responses to disasters.
AB  - The pathogenic effect of extreme events has been equated with their immediate
      stressfulness, and thereby with the biology of stress. This article extends this
      classical view to include, among other pathogenic factors the biological
      dimensions of learning, social interaction, territorial behavior, and a top-down
      brain process that links personal and cultural meanings with emotional and bodily
      responses. The paper depicts the way in which mechanisms related to stress and
      aversive learning trigger an initial response and those related to separation,
      loss and sensitization shape its long-term consequences. Traumatic events are
      followed by a critical period of increased brain plasticity, during which
      irreversible neuronal changes may occur in those who develop traumatic stress
      disorders.

PMID- 10934755
TI  - [Rare complication of myositis in chronic graft-versus-host disease] [In Process
      Citation]

PMID- 10934754
TI  - [Severe myopathy in patients with thyrotoxicosis] [In Process Citation]

PMID- 10934756
TI  - [Cardiac valve diseases and antiphospholipid syndrome] [In Process Citation]

PMID- 10934757
TI  - [Vasculopathy in dermatomyositis] [In Process Citation]

PMID- 10934758
TI  - [Antineutrophil cytoplasmic antibody-related vasculitis and liver diseases] [In
      Process Citation]

PMID- 10934760
TI  - [Reevaluation of laboratory parameters in relation to histological findings in
      primary and secondary Sjogren's syndrome] [In Process Citation]

PMID- 10934759
TI  - [Clinical, serological and genetic study in patients with CREST syndrome] [In
      Process Citation]

PMID- 10934761
TI  - [Treatment of renovascular hypertension using stent implantation in an elderly
      patient with NIDDM] [In Process Citation]

PMID- 10934763
TI  - [Hyperthyroidism presenting as dysphagia] [In Process Citation]

PMID- 10934762
TI  - [Tertiary hyperparathyroidism in X-linked hypophosphatemic rickets] [In Process
      Citation]

PMID- 10934764
TI  - [Malignant insulinoma which expressed a unique creatine kinase isoenzyme:
      clinical value of arterial embolization as a palliative therapy] [In Process
      Citation]

PMID- 10934765
TI  - [Response to combined modality treatment in a five-year survivor of extensive
      small cell lung cancer with severe complications] [In Process Citation]

PMID- 10934767
TI  - [Acute rhombencephalitis: neuroimaging evidence] [In Process Citation]

PMID- 10934766
TI  - [Myositis as a manifestation of chronic graft-versus-host disease] [In Process
      Citation]

PMID- 10934768
TI  - [Myasthenia gravis with membranous nephropathy, successfully treated with
      extended total thymectomy] [In Process Citation]

PMID- 10934770
TI  - [An adult case of mumps brainstem encephalitis] [In Process Citation]

PMID- 10934769
TI  - [Diabetic ketoacidosis associated with Guillain-Barre syndrome with autonomic
      dysfunction] [In Process Citation]

PMID- 10934771
TI  - [Guillain-Barre syndrome following hand-foot-and mouth disease] [In Process
      Citation]

PMID- 10934773
TI  - [Liver abscess accompanied by TTP and Liddle's syndrome-like symptoms].

PMID- 10934772
TI  - [Hypersensitivity vasculitis caused by the herbicide containing the
      isopropylamine salt of glyphosate].

PMID- 10934774
TI  - [Amegakaryocytic thrombocytopenia associated with systemic lupus erythematosus].

PMID- 10934775
TI  - [Multiple myeloma with hyperammonemia].

PMID- 10934776
TI  - [Severe neuro-Behcet with perforation of the intestine].

PMID- 10934777
TI  - [] [In Process Citation]

PMID- 10934778
TI  - Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic
      anemia, diagnosis).
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder in which
      intravascular hemolysis results from the somatic mutation of the totipotent stem
      cells causing an intrinsic defect in red cell membrane. PNH cells lack
      glycosylphosphatidylinositol (GPI) anchored membrane proteins. Of these proteins
      absence of CD 59 (MIRL--membrane inhibitor of reactive lysis, protectin) and CD
      55 (DAF--decay accelerating factor) makes the PNH cells abnormally sensitive to
      the lytic action of complement. The defect appears to be in the somatic mutation
      of the X-linked PIG-A (phosphatidylinositolglycan A class) gene which participate
      in an early step of GPI-anchor synthesis. PNH is characterized by recurrent life
      threatening venous thromboses and an intimate association with aplastic anemia
      (AA). It seems that PNH always coexists with bone marrow failure (BMF) (37). The
      possible explanation may be that some GPI-anchored proteins may be a critical
      target recognized by immune effector cells. PNH clones not possessing these
      critical GPI-anchored proteins will survive because they are selectively
      resistant to the autoimmune assault that eliminates most normal clones. The flow
      cytometry of erythrocytes using anti-CD 59 and anti-CD 59 and anti-CD 55 of
      granulocytes has been now introduced as a very sensitive and quantitative method
      of PNH diagnosis able to detect PNH cells even in normal individuals (1,54). Thus
      it seems now clear that we must make distinction between the detection of very
      occasional PNH cells in patients with BMF and PNH as a clinicohematological
      entity. Unfortunately, we do not know the minimal content of PNH cells required
      to produce clinical signs of PNH (38).

PMID- 10934779
TI  - 3-Nitropropionic acid and similar nitrotoxins.
AB  - 3-Nitropropionic acid as well as 3-nitro-1-propanol and its beta-D
      glucopyranoside (miserotoxin) are the plant and fungal toxins reported to
      interrupt mitochondrial electron transport resulting in cellular energy deficit.
      These nitrotoxins induce neurological degeneration in ruminants and humans. 3
      Nitropropionic acid-intoxicated rats serve as the animal model for Huntington's
      disease.

PMID- 10934780
TI  - Metabolism of tryptophan in the liver: interference with decarboxylation of other
      aromatic amino acids.
AB  - Decarboxylation of aromatic amino acid in mammalian tissues is catalyzed by
      aromatic amino acid decarboxylase (EC. 4.1.1.28, AAD). The enzyme differs in its
      affinity to individual aromatic amino acids, the best substrates being 3,4
      dihydroxyphenylalanine (dopa) and 5-hydroxytroptophan. Surprisingly, AAD is
      abundant in the liver, where the substrates with rather low affinity to AAD as
      tryptophan, phenylalanine, and tyrosine are offered to decarboxylation. In the
      present paper, the possibility of interference of tryptophan with decarboxylation
      of phenylalanine, tyrosine as well as dopa in the liver was investigated. The AAD
      activity was measured radiometrically with 1-14C-labeled aromatic amino acid
      substrates using the rat liver enzyme. The influence of tryptophan on
      decarboxylation of tyrosine was formally competitive with Ki = 9.2 x 10(-3) M,
      while the inhibition of decarboxylation of phenylalanine by tryptophan was non
      competitive with Ki at 2.75 x 10(-2) M. The effect of tryptophan on
      decarboxylation of dopa was small and it could not be expressed in terms of
      inhibition kinetics and inhibition constant. At physiological concentrations of
      aromatic amino acids in plasma, tryptophan does not seem to have remarkable
      effects on decarboxylation of phenylalanine, tyrosine, and dopa in the liver.

PMID- 10934781
TI  - The long-term changes in liver DNA and total protein contents following low level
      sarin exposure in rats.
AB  - 1. The changes in contents of DNA and total protein in the liver of the rats
      exposed to low level sarin by inhalation at 3, 6 and 12 months following the
      exposure were studied. The influence of sarin on the DNA and protein metabolism
      in liver was determined by the measurements of incorporation of tritiated
      thymidine into DNA, the concentration of DNA and total protein. 2. Our results
      show that not only symptomatic level 3 but also asymptomatic levels 1 and 2 of
      sarin are able to significantly decrease the incorporation of radiolabelled
      thymidine without changing total concentrations of DNA as well as protein at
      three months following sarin exposure. On the other hand, the significant
      decrease in total contents of DNA and protein in liver without the changes in the
      incorporation of tritiated thymidine was determined in liver six months following
      sarin exposure. Practically no significant changes in the metabolism of DNA and
      protein were observed at 12 months following sarin exposure. 3. Thus, not only
      clinically manifested intoxication but also low-level, asymptomatic exposure to
      nerve agents such as sarin is able to influence the metabolism of nucleic acids
      as well as proteins even several months following the exposure.

PMID- 10934783
TI  - Sternobronchial fistula--uncommon complication after coronary surgery (a case
      report).
AB  - The authors describe a case of a 46-year-old man with ischemic heart disease who
      underwent coronary surgery. After some time span an inflamed wound, several skin
      fistulae and the system of substernal fistulae appeared. One of these fistulae
      communicated with the left bronchial tree.

PMID- 10934782
TI  - Changes of the serum antibiotic levels during open heart surgery (ceftazidim,
      ciprofloxacin, clindamycin).
AB  - BACKGROUND: Wound, mediastinal and intracardiac infections are still very serious
      complications of open-heart surgery. The incidence of it is still in the range of
      0.4%-5%. The aims of our study were to assess the adequacy of regimen using
      ceftazidim (CTZ), ciprofloxacin (CPF) and clindamycin (CLIN) as prophylactic
      antibiotics and to verify whether cardiopulmonary bypass (CPB) can modify the
      time of antibiotic serum concentrations. That is why the serum levels of them
      were measured during open heart procedures. METHODS: The prospective study
      comprised 75 consequent coronary patients randomized in to three groups receiving
      1 g of CTZ or 400 mg of CPF or 900 mg of CLIN i.v. with anesthesia induction.
      Routine coronary surgery with left internal mammary artery harvesting, moderate
      body hypothermic (30 degrees C) CPB with crystaloid cardioplegia was performed.
      Serum antibiotic levels were determined before application, with skin incision,
      prior CPB induction, after cardioplegia infusion, every 20 minutes of CPB, prior
      end of CPB, in time of chest closure. Conventional cylinder-plate microbiological
      assay was used for antibiotic level measurement. RESULTS: All serum antibiotic
      concentrations showed a sharp decrease immediately after starting CPB and lasted
      until CPB ended. After initiating of CPB after cardioplegia administration serum
      concentrations of CTZ (105 min after initial dose) decreased by, on average 55%,
      CPF (97 min) by 42% and CLIN (116 min) by 78%. CONCLUSION: CPB can modify the
      time course of antibiotic serum concentrations. The serum levels of CTZ at the
      end of the longest procedures were found to be below the MICs for some of the
      suspected pathogens. We recommend to use higher antibiotic doses for prophylaxis
      and to administer the second dose with protamin sulphate to obtain maximum
      concentration in newly formed blood clots.

PMID- 10934784
TI  - Application of infrared spectrophotometry to the identification of inorganic
      substances in dosage forms of Antacida group.
AB  - Powdered tablets from the Antacida group: Alusal, Milk of Magnesia, Alumag,
      Maalox, Magnosil, Alugastrin, Malugastrin, Rennie, and components deciding about
      their antiacidity like Al(OH)3, Mg(OH)2, Mg2Si3O8, NaAl(OH)2CO3, MgAl(OH)(SO4)2,
      CaCO3, MgCO3, were subjected to infrared spectrophotometric investigations. It
      was found that infrared spectra of each pharmaceutical compound are different and
      show a series of characteristic maxima, by which they can be identified with in
      the spectral range of 4000 cm-1-200 cm-1. Comparison of infrared spectra of
      finished products with spectra of their components it was showed that the
      application of infrared spectrophotometry methods enabled us to prove the
      presence of particular compounds used in formulations. Tablet mass and odorizing
      agents do not cause significant changes in spectra of the tablets studied,
      preparations from the Antacida group.

PMID- 10934785
TI  - Gravimetric and spectrophotometric determination of some drugs--tertiary amine
      hydrochlorides in coated tablets.
AB  - Four drugs in the form of coated tablets: Amitryptylinum (Amitryptyline) (1),
      Imipramin (Imipramine) (2), Chloropyribenzaminum (Chloropyramine) (3), and
      Phenazolinum (Antazoline) (4) were determined gravimetrically and
      spectrophotometrically in the same process by using complexes with ammonium
      molybdate. Stoichiometry of the complexes was established by elemental analysis
      and analysis of the incineration residue (MoO3). The complexes were characterized
      by IR and UV spectra and melting points. Contents of the drugs in the complexes
      were also determined spectrophotometrically. In this method Beer's law was found
      to obey over the concentration ranges 10-80 micrograms/ml (complex of 1), 10-100
      micrograms/ml (complexes of 2 and 3), and 10-60 micrograms/ml (complex of 4).
      This method was validated in terms of precision, linearity, limit of detection
      and limit of quantitation. The two methods of the drug determination used in a
      single process of analysis, verify each other.

PMID- 10934786
TI  - The dissolution kinetics of sulfamethoxazol, trimethoprim and oxytetracycline
      hydrochloride from multicomponent solid dispersion capsules ("Sulfoxytrim").
AB  - Release profiles and dissolution kinetics of active substance, viz.
      sulfamethoxazol (SMO), trimethoprim (TMP), and oxytetracycline hydrochloride
      (OTC) from capsulated multicomponent dispersions was studied in a flow-cell
      apparatus at 37 degrees C by using a dissolution medium of 0.1 mol/l HCl. The
      results revealed that the relative dissolution efficiency (DE) and dissolution
      profiles of one active ingredient were affected by the presence of the two
      others. Vitamin C added caused the decreased the dissolution rate constants (K)
      and DE--values of all the active substances studied.

PMID- 10934787
TI  - A bioequivalence study of two brands of glipizide tablets.
AB  - In this open, randomized, two way crossover, bioequivalence study, two 5 mg
      tablet preparations of glipizide (Glipizyd tabl. 5 mg, Tarchominskie Zaklady
      Farmaceutyczne POLFA S.A., and Glibenese tabl. 5 mg, Pfizer), were compared in 24
      healthy male volunteers. Pharmacokinetic variables (mean maximum plasma
      concentration, mean time to reach maximum plasma concentration, and the mean area
      under the plasma concentration-time curve) were not statistically significantly
      different for the two formulations. It can be concluded that the two tablet
      preparations of glipizide are likely to be bioequivalent.

PMID- 10934788
TI  - The in vitro study of influence of antioxidant enzymes level and repair capacity
      on cytotoxic bleomycin activity in human and mouse cells.
AB  - Bleomycin, an antitumour antibiotic was used to study the possible relationship
      between DNA single strand breaks repair capacity, antioxidant enzymes level and
      cytotoxic activity of the drug in mouse cells: AKR and BALB/c and in human cells:
      CRL 2088 and CRL 1307 (xeroderma pigmentosum). The BALB/c and CRL 1307 cells were
      used because of having defects in DNA repair capacity. A positive correlation was
      shown to exist between IC50 values and repair ability which suggested that DNA
      single strand breaks could be responsible for cytotoxic effects of bleomycin in
      human and mouse cells. Also antioxidant enzymes level have occurred as, at least
      partly, participating in bleomycin cytotoxic efficiency. About 10-fold higher
      resistance of AKR cells to bleomycin in comparison with the other cells, as
      appeared here, did not exhibit the straight correlation with antioxidant status
      of the cells. It prompts participation of the other mechanism in bleomycin
      cytotoxic action than that based on free radical generation. Also drug
      distribution and metabolism should be considered as a possible factor needed in
      bleomycin efficacy evaluation.

PMID- 10934790
TI  - A study on some 4,5-dihydro-1H-1,2,4-triazol-5-one derivatives.
AB  - Fourteen new potentially biologically active 4,5-dihydro-1H-1,2,4-triazol-5-one
      derivatives were synthesized and characterized by elemental analysis, 1H NMR, IR
      and UV spectra. Three of these compounds were screened for their antitumor
      activities.

PMID- 10934789
TI  - The influence of low H2O2 concentrations on DNA content distribution in cell
      cycle and expression of cyclins in human cells.
AB  - The previous study has shown several cell lines pretreated with a low dose of
      hydrogen peroxide to exhibit an adaptive response to subsequent high doses of
      adriamycin. We undertook the present investigation to examine whether a
      relationship exists between the hydrogen peroxide pretreatment and perturbation
      in the phases of the cell cycle observed as the changes in DNA content
      distribution. We utilized human embryo cells, human melanoma cells and human
      melanoma adriamycin resistant subline, experimental developed. The data obtained
      in the present study suggest that hydrogen peroxide at low concentration can
      modify the normal rate of cell cycle progression.

PMID- 10934791
TI  - Synthesis of aminomethyl derivatives of 4-phenyl-1,2,4-triazolin-5-one-1-acetic
      acid amide and 3,4-diphenyl-1,2,4-triazolin-5-one-1-acetic acid amide.
AB  - Ehtyl esters of 4-phenyl-1,2,4-triazolin-5-one-1-acetic acid and 3,4-diphenyl
      1,2,4-triazolin-5-one-1-acetic acid were transformed into the corresponding
      amides [Ia, b]. The aminomethylation reactions afforded Mannich bases [IIa, b
      VIa, b] exhibiting the expected pharmacological effects.

PMID- 10934792
TI  - Apigenin glycosides from the flowers of Bellis perennis L.
AB  - Two next apigenin glycosides, apigenin 7-O-beta-D-glucuronide [III], apigenin 7-O
      beta-D-glucoside [IV] were isolated from the flowers of Bellis perennis L. Their
      structures were determined by means of chemical and spectroscopic methods.

PMID- 10934793
TI  - Pregnadienolone glycoside from wild garlic Allium ursinum L.
AB  - A thorough investigation of saponin fraction from the underground parts of wild
      garlic--Allium ursinum L. (Liliaceae) has led to the isolation of 3-[O-alpha
      rhamnopyranosyl-(1-->4)-alpha-rhamnopyranosyl-(1-->4)- alpha-rhamnopyranosyl-(1-
      >4)-beta-glucopyranoside-(1-->)]-3 beta-hydroxypregna-5,16-dien-20-one [1]. The
      structure of 1 was established by chemical and spectroscopic methods. Compound 1
      is reported for the first time.

PMID- 10934794
TI  - Biological properties of genistein. A review of in vitro and in vivo data.
AB  - Genistein--a soy derived isoflavone has recently attracted much attention of the
      medical scientific community. This compound was found to be a potent agent in
      both prophylaxis and treatment of cancer as well as other chronic diseases. The
      great interest that has focused on genistein led to the identification of
      numerous intracellular targets of its action in the live cell. At the molecular
      level, genistein inhibits the activity of ATP utilizing enzymes such as: tyrosine
      specific protein kinases, topoisomerase II and enzymes involved in
      phosphatidylinositol turnover. Moreover, genistein can act via an estrogen
      receptor-mediated mechanism. At the level one step higher, i.e., at the cellular
      level, genistein induces apoptosis and differentiation in cancer cells, inhibits
      cell proliferation, modulates cell cycling, exerts antioxidant effects, inhibits
      angiogenesis, and suppresses osteoclast and lymphocyte functions. These
      activities make genistein a promising innovative agent in the treatment of
      cancer. Additionally, genistein health beneficial effects have been shown in
      osteoporosis, cardiovascular diseases and menopause. Genistein was also
      successfully used as an immunosuppressive agent both in vitro and in vivo. All
      these effects at the three biological levels of action need varied genistein
      concentrations and only some of them are relevant in people consuming soy-rich
      diet. The others would occur after purified genistein administration at higher
      doses. The main genistein advantage as a potential drug is its multidirectional
      action in the live cell and its very low toxicity.

PMID- 10934795
TI  - An evaluation of different approaches for behavior genetic analyses with
      psychiatric symptom scores.
AB  - We used a simulation study to evaluate six approaches for behavior genetic
      analyses of psychiatric symptom scores. For the selection of the correct model,
      the best results were obtained with approaches using transformed scores in
      combination with a procedure involving p-values. With normalizing
      transformations, the chi 2 test statistic gave a reasonable impression of the
      overall fit of the model but was less accurate when used as a difference test.
      The asymptotic distribution free estimation methods yielded chi 2s that were much
      too large. All data analysis techniques yielded substantially biased parameter
      estimates. The most biased results were obtained with normalizing
      transformations. The least biased results were obtained with tobit correlations,
      but because of its large standard errors the most precise estimates were obtained
      with polychoric correlations and optimal scale scores. An empirical study showed
      that a recognition of the role of methodological factors was helpful to
      understand part of the differences between assessment instruments, raters, and
      data analysis techniques that were found in the real data.

PMID- 10934796
TI  - Dimensions of psychological masculinity-femininity in adult twins from opposite
      sex and same-sex pairs.
AB  - Male and female twins with opposite-sex co-twins were compared to twins with same
      sex co-twins on three independent dimensions of masculinity-femininity, in order
      to examine the hypothesis that the hormones of the co-twin might have an effect
      on prenatal masculinization. The analysis was originally carried out for an older
      cohort from the Australian Twin Registry (2647 pairs, mean age 41.2), and then
      repeated in a younger cohort (1503 pairs, mean age 23.2). For women, the results
      on two of the three scales support and extend that of an earlier large study in
      Finland by Rose et al. (1994), who found no effect of sex of co-twin on feminine
      interests. One of the two scales contrasted worried and calm individuals, the
      other, confiding and reserved ones. The third scale, willingness to break or bend
      rules, showed a small effect of shared environmental influence, and it lay in the
      expected direction for a prenatal hormonal effect--females with a male co-twin
      scored higher (more like males). Most previous studies have not looked at the
      effect of sex of co-twin on males. The present study detected several such
      effects, although all were small in magnitude. The pattern was complex: sometimes
      the effect was in the masculine direction, sometimes in the feminine direction;
      sometimes there was agreement between the older and younger cohorts, sometimes
      not. Overall, the results suggest that no simple masculinization hypothesis-
      prenatal or postnatal--will adequately account for all the evidence. Age, sex,
      and aspect of masculinity-femininity must be taken into account.

PMID- 10934797
TI  - Genetic factor analyses of specific cognitive abilities in 5-year-old Dutch
      children.
AB  - The genetic and environmental factor structures of intellectual abilities in 5
      year-old Dutch twins were examined. Six subtests of the RAKIT, a Dutch
      intelligence test, were administered to 209 twin pairs. The subtests were
      categorized as either verbal or nonverbal. The genetic covariance structure
      displayed a two-common factor structure including specific factors to account for
      subtest residual variance. The correlation between the genetic Verbal and genetic
      Nonverbal factors did not differ significantly from zero. The shared
      environmental influence displayed a single-common factor structure. Unique
      environmental influences did not contribute to the covariance between subtests
      and were specific in origin. Estimates of heritability of the subtests ranged
      from 15% to 56%. Shared environmental influences were significantly present, but
      were modest in magnitude. The phenotypic data was best described by an oblique
      two-factor model. This model was not mirrored in the factor structures found for
      either the genetic or environmental covariances.

PMID- 10934798
TI  - Evaluation and extensions of a structural equation modeling approach to the
      analysis of survival data.
AB  - Recently a new method for the analysis of survival data using a structural
      equation modeling approach has been suggested by Pickles and colleagues using
      twin data they demonstrated the application of this model to study the
      correlation in age of onset. The purpose of the current research is twofold: 1)
      to evaluate the statistical performance of the model as presented by Pickles and
      colleagues, and 2) to expand and evaluate the model in more applications,
      including both genetically informative data and other multivariate examples.
      Results evaluated from this study involve three areas of method performance: Type
      I error rates, power, and parameter estimates under four different distributions
      (normal, Gamma-2, Gamma-6 and g-and-h) and four different sample sizes (n = 125,
      250, 500 and 750). Results based on the original Pickles model indicated that in
      all sample size and distribution conditions the Type-I error rate was adequate,
      in fact below the nominal level of .05. Additionally, power was greater than .80
      for sample sizes of 500 or more for all distribution conditions. Parameter
      estimates were upwardly biased when the population value was rho = .20. This bias
      varied across distributions; the g-and-h distribution showed the largest bias.
      Results from the expanded model indicated that Type-I error rates were adequate.
      Power results were not affected by distribution type; sample sizes of 500 were
      above the .80 level. Parameter estimates continued to be upwardly biased in this
      more general model, although the degree of bias was smaller.

PMID- 10934799
TI  - Physical similarity and twin resemblance for eating attitudes and behaviors: a
      test of the equal environments assumption.
AB  - The Equal Environments Assumption (EEA) in twin studies of eating pathology was
      investigated by examining the hypothesis that twin resemblance for eating
      attitudes and behaviors is affected by their degree of physical similarity.
      Eating attitudes and behaviors were assessed in 338 female adolescent twin pairs
      with a revised version of the Eating Disorder Inventory (EDI). General physical
      similarity as well as body size/shape similarity were assessed using ratings of
      color photographs, ratings of body shape, and body mass index. All physical
      similarity assessments were conducted blind to twin zygosity. Significant
      associations between physical similarity and twin similarity for eating attitudes
      and behaviors were not found. Mean EDI within-twin pair absolute difference
      scores did not differ significantly among more versus less physically-similar
      groups. Additionally, correlation and regression analyses failed to find a
      significant association between EDI absolute difference scores and physical
      similarity indices. The current findings provide support for the EEA in twin
      studies of eating attitudes and behaviors.

PMID- 10934800
TI  - Behavioral characterization and genetic analysis of the Drosophila melanogaster
      larval response to light as revealed by a novel individual assay.
AB  - A new assay was designed, named checker, that measures the individual response to
      light in the fruitfly Drosophila melanogaster larva. In this assay the Drosophila
      larva apparently modulates its pattern of locomotion when faced with a choice
      between a dark and lit environment by orienting its movement towards the dark
      environment. We show that, in this assay, a response to light can be measured as
      an increase in residence time in the dark versus the lit quadrant. Mutations that
      disrupt phototransduction in the adult Drosophila abolish the larval response to
      light, demonstrating that this larval visual function is similar to that of the
      adult fly. Similarly, no response to light was detected in strains where the
      larval visual system (photoreceptors and target area) was disrupted by a mutation
      in the homeobox containing gene sine oculis (so) gene. Ablation of photoreceptors
      by the targeted expression of the cell death gene hid under the control of the
      photoreceptor-specific transcription factor glass (gl) abolishes this response
      entirely. Finally, we demonstrate that this response to light can be mediated by
      rhodopsins other than the blue absorbing Rh1.

PMID- 10934802
TI  - Inheritance of pendulum movements in rats.
AB  - The stereotyped hyperkinesis referred to as pendulum movements (PM) may be found
      in up to 50% of the animals in stocks of Wistar rats. The mode of inheritance of
      predisposition to PM was studied by two methods: 1) a classical Mendelian
      analysis of hybrids of the strains PM+ and PM- bred from Wistar stock for
      enhancement and absence of PM, respectively, and 2) a segregation analysis of
      pedigree data from the archive records of breeding the cataleptic GC strain. The
      two methods gave the same result: the inheritance of predisposition to PM can be
      explained by a major gene model with an incomplete penetrance of heterozygous
      genotype.

PMID- 10934801
TI  - Differential effects of cohort removal stress on the acoustic startle response of
      the Roman/Verh rat strains.
AB  - Male and female rats of the inbred Roman/Verh strains, which have been
      psychogenetically selected and bred for good (RHA-I/Verh) and extremely poor (RLA
      I/Verh) two-way avoidance acquisition, were evaluated in an acoustic startle
      response test. One half of the rats of each strain and sex were previously
      subjected to 30 min of isolation by removal of their cage partners ("cohort
      removal"). During the testing session each animal received 40 acoustic stimuli at
      interstimulus intervals of 30 seconds. The hyperemotional RLA-I/Verh rats
      (especially the males) showed stronger acoustic startle responses than did their
      RHA-I/Verh counterparts. Startle amplitudes of the RLA-I/Verh males were further
      enhanced by the stress of 30 min isolation, whereas cohort removal did not
      significantly affect startle response amplitudes in RHA-I/Verh rats of either sex
      or in females of the RLA-I/Verh strain.

PMID- 10934803
TI  - Combination versus alternating chemotherapy in small-cell lung cancer.
AB  - BACKGROUND: The major obstacles in the treatment of small-cell lung cancer (SCLC)
      are tumor recurrence and the emergence of drug resistance to chemotherapeutic
      agents. Using alternating non-cross-resistant combination regimens is an
      attractive strategy, but the efficacy and toxicities are still controversial.
      METHODS: Previously untreated SCLC patients were randomly assigned to standard
      CEOV therapy (cyclophosphamide, epirubicin, vincristine = oncovin, and etoposide
      = VP-16) or CEOV alternating with CAM therapy (cyclophosphamide, ACNU and
      methotrexate). Chemotherapy was repeated every 4 weeks for a total of eight
      cycles. Complete and partial responders were administered thoracic irradiation.
      RESULTS: Between July 1987 and July 1993, 150 patients were enrolled and 123 were
      evaluable. There was no significant superiority in the treatment outcome for CEOV
      CAM therapy over CEOV therapy in terms of overall response rate (51% vs 71%),
      complete response rate (9% vs 35%), median survival time (9.5 months vs 12.0
      months) and 2-year survival rate (7% vs 13%). Both patients with limited disease
      and extensive disease had equal response rates to the CEOV regimen (70% and 71%,
      respectively). However, patients with limited disease had a significantly higher
      response rate to the CEOV-CAM regimen than did patients with extensive disease
      (65% vs 36%, p = 0.04). Toxicities for both treatment arms were comparable.
      Patients who achieved complete or partial response received thoracic irradiation
      and had significantly longer survival than responders who did not receive
      thoracic irradiation (14.0 months vs 12.0 months, p = 0.02). There were equal
      chances of tumor recurrence in the chest and at distant sites (66% vs 67%) in the
      CEOV arm. However, in the CEOV-CAM arm, tumors were more likely to occur in the
      chest than in distant sites (86% vs 36%) (p = 0.0016). CONCLUSIONS: We concluded
      that alternating chemotherapy provides no therapeutic advantage compared with
      four-regimen combination chemotherapy in terms of tumor response, median survival
      and 2-year survival rate for SCLC patients. Early thoracic irradiation should be
      applied to achieve better local control and less distant recurrence for
      chemotherapy responders.

PMID- 10934804
TI  - Clinical experience in using polymerase chain reaction for rapid diagnosis of
      pulmonary tuberculosis.
AB  - BACKGROUND: Polymerase chain reaction (PCR) techniques have revolutionized the
      diagnosis of tuberculosis (TB). PCR has significantly improved the sensitivity
      and specificity of existing diagnostic methods. In this study, we report our
      experience using a modified IS6110-based nested PCR assay for rapid diagnosis of
      pulmonary TB. METHODS: A total of 327 respiratory specimens from 275 patients
      suspected of having pulmonary TB at Taipei Veterans General Hospital were tested
      using the nested PCR assay, acid-fast smear and culture for the presence of
      Mycobacterium tuberculosis complex (MTB). Nested PCR was performed with IS6110
      based primers specific for MTB. We reviewed the medical records of patients and
      analyzed the clinical features. The PCR results were compared with the final
      clinical diagnosis. RESULTS: We identified MTB in 167 of 327 samples by the
      nested PCR assay. No non-tuberculous Mycobacterium (NTM) was identified among the
      clinical samples. Diagnosis by PCR took about 6 hours in this study. The
      sensitivity and specificity compared with culture were 94.7% and 100%,
      respectively for the smear-positive, culture-positive samples, and 76.7% and
      98.6% for the smear-negative, culture-positive samples. The overall sensitivity,
      specificity, positive and negative predictive values, compared with culture
      results, were 91.7%, 98.6%, 98.8% and 90.6%, respectively. Two specimens positive
      by PCR and negative by culture were taken from patients on anti-TB drug therapy.
      These specimens were culture-positive before anti-TB drug therapy. After
      resolution of the discrepancies by studying the patients' clinical data, both
      specificity and positive predictive value reached 100%. CONCLUSIONS: The results
      indicated that this in-house nested PCR assay is a rapid and sensitive method for
      diagnosing pulmonary TB. It is also good for excluding infections caused by NTM.

PMID- 10934805
TI  - Clinical, virologic and pathologic significance of elevated serum gamma-glutamyl
      transpeptidase in patients with chronic hepatitis C.
AB  - BACKGROUND: Elevated serum gamma-glutamyl transpeptidase (GGT) is often seen in
      patients with chronic hepatitis C virus (HCV) infection and is associated with a
      poor response to interferon treatment. The pathogenesis of these phenomena is
      unclear. Therefore, we assessed the prevalence of elevated serum GGT in Chinese
      patients with chronic hepatitis C and evaluated the clinical, biochemical,
      virologic and histologic features of this phenomenon. METHODS: One hundred and
      twelve patients with biopsy-proven chronic hepatitis C were enrolled. Patients
      who were habitual alcohol drinkers, alcoholics or had diabetes mellitus were
      excluded. RESULTS: Forty-three (38.4%) of 112 patients had elevated serum GGT (>
      60 U/l). Patients with elevated serum GGT had significantly higher serum levels
      of alanine and aspartate aminotransferases, alkaline phosphatase and total
      bilirubin, significantly higher histologic scores of liver lobular necro
      inflammation and fibrosis when compared to patients with normal serum GGT.
      Elevated serum GGT was not correlated to serum HCV RNA titer or HCV genotype.
      Multivariate logistic regression analysis showed that a histologic fibrotic score
      > or = 2 was the only significantly independent predictor associated with
      elevated serum GGT. Fifty-seven of 112 patients completed a six-month course of
      interferon treatment. Patients with elevated serum GGT had a significantly lower
      sustained response rate to interferon when compared to patients with normal serum
      GGT (8% vs 30%, p = 0.042). CONCLUSIONS: Elevated serum GGT in chronic hepatitis
      C patients was frequently associated with more severe hepatic fibrosis or
      cirrhosis and may, in part, account for poor response to interferon therapy.

PMID- 10934806
TI  - Sauropus androgynus and papaverine do not induce bronchiolitis obliterans in
      Sprague-Dawley rats.
AB  - BACKGROUND: In August 1995, an outbreak of bronchiolitis obliterans was observed
      in Taiwan. This progressive respiratory distress disease was associated with
      consumption of the uncooked vegetable, Sauropus androgynus. The vegetable is
      reportedly high in papaverine, a chemical that affects vasodilatation. This study
      determined whether S androgynus and papaverine induce bronchiolitis obliterans in
      Sprague-Dawley (S/D) rats. METHODS: The feeding doses were derived from the mean
      amount (in mg/kg body weight) that humans had eaten. In part A of the experiment,
      30 S/D rats were fed various concentrations of S androgynus juice for eight
      weeks. The rats were divided into six groups, including a normal control and
      study groups with one time (1X), 10 times (10X, leaf only and mixed leaf and
      stalk) and 30 times (30X, leaf only and mixed leaf and stalk) concentration. In
      part B, 33 S/D rats were fed different doses of papaverine for 4 weeks. The rats
      were also divided into six groups, including normal control, oral feeding
      subgroups (1X, 10X and 20X) and intraperitoneal injection subgroups (5X and 10X).
      The degree of inflammation was defined semiquantitatively in the bronchioles and
      pulmonary vessel adventitia as including grade 0 (no inflammation), grade 1
      (minimal), grade 2 (mild), grade 3 (moderate) and grade 4 (severe). RESULTS:
      There was no evidence of bronchiolitis obliterans in either experiment. The
      histopathologic findings of the lungs revealed normal or only minimal
      inflammatory changes in the peribronchial and perivascular adventitia in each
      group of both studies. The mean degree of inflammatory changes in the study
      groups was no different from that of control group. CONCLUSIONS: We conclude that
      ingestion of high-dose S anggogynus and papaverine do not induce injuries to the
      airways, alveoli or pulmonary vessels in the animal model of S/D rats. The
      species barrier may be one of the possible reasons.

PMID- 10934807
TI  - Comparison of bilevel positive airway pressure and volume ventilation via nasal
      or facial masks in patients with severe, stable COPD.
AB  - BACKGROUND: In the past decade, noninvasive positive pressure ventilation (NIPPV)
      has been successfully used in chronic obstructive pulmonary disease (COPD) with
      acute exacerbation. Nonetheless, its effect in stable COPD remains controversial.
      Theoretically, differences in the mode of ventilation such as pressure versus
      volume preset, or interfaces such as nasal versus full facial mask could have an
      impact on the efficacy of NIPPV. Few published studies have focused on this
      topic. METHODS: In this crossover study, bilevel positive airway pressure (BiPAP)
      for pressure preset ventilation or PLV-100 as a home-care volume preset
      ventilator was used via a nasal or facial mask in 12 patients with stable
      hypercapnic COPD. The four types (2 ventilators and 2 masks) of NIPPV were used
      for 20 minutes each, with a randomized sequence. The patient breathed
      spontaneously for 10 minutes before and between each type of NIPPV as a baseline
      for comparison. RESULTS: Respiratory rate, tidal volume, pulse rate, Borg scale
      and phase angle were all significantly improved during BiPAP ventilation via
      either a nasal or facial mask (p < 0.05 for all). Suppression of inspiratory
      muscle activity was obvious, although not statistically significant. In contrast,
      inspiratory muscle activity, phase angle and respiratory rate increased and tidal
      volume decreased significantly during PLV-100 ventilation with either nasal or
      facial masks (p < 0.05 for all). Peak expiratory flow rate and maximum
      inspiratory and expiratory mouth pressures remained unchanged after each type of
      NIPPV. CONCLUSIONS: For patients with stable hypercapnic COPD, short-term use of
      BiPAP via either a nasal or facial mask markedly rests the inspiratory muscles,
      improves the respiratory pattern and reduces the sense of dyspnea for patients.
      In contrast, short-term use of PLV-100 via either a nasal or facial mask worsens
      the above parameters.

PMID- 10934808
TI  - Reanalysis of stone manipulation prior to extracorporeal shock wave lithotripsy
      for management of upper ureteral calculi.
AB  - BACKGROUND: In situ extracorporeal shock wave lithotripsy (ESWL) for upper
      ureteral stones is controversial, in contrast to ESWL treatment of the majority
      of other renal calculi. Some urologists recommend retrograde mobilization of the
      calculi into the renal pelvis prior to ESWL as a routine procedure, while others
      report little advantage in manipulating a ureteral stone into the kidney before
      treatment by ESWL. To better understand this controversial issue, we reanalyzed
      clinical studies and the mechanism of stone disintegration in ESWL. METHODS: We
      performed a computerized MEDLINE search and manual bibliographic review of
      relevant peer reviewed reports from 1980 to 1998. Ten reports were analyzed with
      respect to stone-free rate and the important findings are summarized. RESULTS:
      Two of 10 data sets are statistically significant (p < 0.05) to verify a higher
      stone-free rate and another five reports also revealed that higher stone-free
      rates could be expected with retrograde stone manipulation into the renal
      collecting system before treatment by ESWL. CONCLUSIONS: Higher stone-free rates
      with retrograde stone manipulation into the renal collecting system before
      treatment by ESWL is statistically significant and theoretically supported by the
      mechanism of stone disintegration.

PMID- 10934810
TI  - Associations between lipoprotein lipase gene polymorphisms and insulin resistance
      in coronary heart disease.
AB  - BACKGROUND: Lipoprotein lipase (LPL) is a crucial enzyme in plasma lipoprotein
      metabolism. Variants of the LPL gene (Pvu II and Hind III polymorphisms) may
      increase the risk of developing coronary heart disease (CHD) but their effect on
      insulin resistance remains unknown. The present study was conducted to examine
      whether DNA variations of the LPL gene were related to insulin resistance,
      carbohydrate and lipid risk factors for CHD in nondiabetic individuals. METHODS:
      Pvu II and Hind III allele status of the LPL gene and fasting plasma glucose,
      insulin and lipid values were determined in nondiabetic men with angiographically
      documented CHD (n = 102) and in a control group (n = 145). Plasma glucose and
      insulin responses to a 75-g oral glucose tolerance test and insulin resistance as
      measured by an insulin suppression test were also carried out in 46 (45%) of the
      patients with CHD and in 73 (50%) of the control individuals. RESULTS: The allele
      frequencies of LPL Pvu II and Hind III were not significantly different between
      the CHD patients and the controls. No association was found between Pvu II status
      and blood pressure, fasting plasma glucose, insulin, lipid levels or insulin
      resistance in patients with CHD. Nevertheless, compared with individuals with the
      Hind III H2H2 allele, CHD patients carrying the H1 allele (H1H1 + H1H2) were more
      insulin resistant, as indicated by higher steady state plasma glucose
      concentrations (253 +/- 87 vs 200 +/- 74 mg/dl, p = 0.032). CONCLUSIONS: We
      suggest that the LPL gene Hind III allele might be associated with insulin
      resistance in nondiabetic men with CHD. However, further studies with larger
      populations of both sexes will be required to confirm this finding.

PMID- 10934811
TI  - Diffuse multiple coronary arteries to left ventricular fistulas.
AB  - Coronary artery to left ventricular fistula is an unusual anatomic anomaly
      consisting of a communication between one of the coronary arteries and the left
      ventricle. Only sporadic cases have been published in the literature. Diffuse
      multiple fistulas involving both left and right coronary arteries are even rarer.
      This report describes a 60-year-old woman with diffuse multiple fistulas
      communicating between both coronary arteries and the left ventricle. The patient
      manifested clinically with exertional angina and myocardial ischemia, as
      evidenced by a positive stress exercise test, which represents the coronary
      "steal" phenomenon.

PMID- 10934809
TI  - Transrectal ultrasonographic findings in patients with hemospermia.
AB  - BACKGROUND: Hemospermia causes anxiety in many men. Its etiology includes
      inflammatory disorders, vascular lesions, malignancies and congenital anomalies.
      With the advent of modern transrectal ultrasonography (TRUS) and magnetic
      resonance imaging technology, we can now visualize the internal structures of the
      seminal vesicles and prostate, and identify a more accurate etiology for
      hemospermia. This study was performed to assess the efficacy of TRUS in the
      evaluation of hemospermia. METHODS: TRUS was used to evaluate 40 patients with
      hemospermia. Patients' ages ranged from 20 to 72 years, with an average age of 41
      years. The duration of symptoms was 3 days to 10 years, (average age 12.4
      months). Apart from three patients with hepatitis, there was no major illness
      found in the medical histories. TRUS was performed with a B & K, type 3535
      transrectal transducer device, with an 1850 multiplane probe. RESULTS: TRUS
      revealed abnormalities in 33 (83%) of 40 patients, which included ejaculatory
      duct cysts, mullerian duct cysts, asymmetric seminal vesicle dilatation,
      preprostatic vein engorgement and prostatic enlargement. There were stones in the
      ejaculatory ducts, ejaculatory duct cysts, mullerian duct cysts or prostate. Nine
      patients with prostatic stones were under 40 years-of-age. Other than the
      development of stones, there were no significant differences between patients
      less than 40 years-of-age and those more than 40 years old. CONCLUSIONS: The
      results suggest that TRUS is an effective method for examining the seminal
      vesicles, ejaculatory duct and prostate complex. Sonoguided aspiration, injection
      of contrast medium or biopsy can further help to differentiate the nature of
      hemospermia.

PMID- 10934812
TI  - Acute scrotum in Henoch-Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is a systemic vasculitis with manifestations
      usually involving the skin, gastrointestinal tract, kidney and joints.
      Epididymitis is rarely seen as a complication of HSP. It is easily misdiagnosed
      as testicular torsion, causing the patient to undergo unnecessary surgery,
      because the patient may have complained of severe scrotal pain and swelling. We
      report a 5-year-old boy who was suffering from HSP associated with acute scrotal
      pain and swelling of the left testicle. No gastrointestinal signs were noted but
      severe joint pain, swelling and palpable skin lesions in the lower limbs and the
      buttocks were found. Prednisolone was prescribed and the boy recovered without
      surgical intervention.

PMID- 10934813
TI  - Prenatal diagnosis and management of congenital cystic adenomatoid malformation.
AB  - Congenital cystic adenomatoid malformation (CCAM) is a rare pulmonary
      malformation resulting from excessive overgrowth of the terminal bronchioles. We
      present two CCAM case studies: type I (macrocystic) and type III (microcystic),
      diagnosed by antenatal ultrasonography at 31 and 21 weeks' gestation,
      respectively. In the former, multiple dilated cystic masses in the fetal left
      lung, with polyhydramnios, were identified during the antepartum examination. A
      postnatal thoracotomy with lobectomy was performed due to persistent cyanosis and
      resulted in a good outcome. In the latter case, an echogenic mass with multiple
      cysts in the fetal right lung was detected by prenatal sonography. The parents
      decided to terminate the pregnancy after prenatal counseling.

PMID- 10934814
TI  - Cavernous sinus gas.
AB  - Gas within the cavernous sinus is an unusual finding. We report three patients
      who demonstrated gas in the cavernous sinus on computerized tomography (CT). The
      clinical information of these patients was reviewed for the possible source of
      the gas and the symptoms induced by the gas. Cavernous sinus gas was seen in two
      patients with sphenoid sinus fracture and in one patient after intravenous fluid
      infusion. None of the patients had symptoms referable to the cavernous sinus gas,
      but one patient had a grave prognosis due to trauma. Identification of cavernous
      sinus gas on CT and correlation with the clinical information is mandatory for
      further management.

PMID- 10934815
TI  - Variant Creutzfeldt-Jakob disease in Leicestershire.

PMID- 10934816
TI  - Outbreak of hospital acquired legionnaires' disease.

PMID- 10934818
TI  - Great gods and little flies.

PMID- 10934817
TI  - Peer review: phony data, shoddy work or revolutionary results? "Truth will out".

PMID- 10934819
TI  - Blood-borne pathogen education: please pass it on!

PMID- 10934820
TI  - Hepatitis B: the only vaccine-preventable bloodborne pathogen.

PMID- 10934821
TI  - Hepatitis C infection: opportunity for exposure in many settings.

PMID- 10934822
TI  - Occupational HIV exposure.

PMID- 10934823
TI  - Non-occupational postexposure HIV prophylaxis: clinical issues and public health
      questions.

PMID- 10934824
TI  - Accidental blood exposures: a frontline perspective.

PMID- 10934825
TI  - Sample cases of exposure.

PMID- 10934826
TI  - Rhode Island's Syringe Exchange Program (ENCORE).

PMID- 10934827
TI  - Blood-borne pathogens, the physician and the Board of Medical Licensure and
      Discipline.

PMID- 10934828
TI  - Neurocysticercosis.

PMID- 10934829
TI  - How does Rhode Island rank nationally on quality indicators?

PMID- 10934830
TI  - [Morphologic changes in the interventricular septum and the posterior wall of the
      left ventricle in patients on hemodialysis].
AB  - Left ventricular hypertrophy is dominant finding in patients with chronic renal
      failure. In our work we have analysed the interventricular septum and left
      ventricular posterior wall in thirty patients on chronic hemodialysis, using an
      echocardiography. Increased thickness of interventricular septum and left
      ventricular posterior wall were found in 70% patients. We have also confirmed
      correlation between these parameters and value of systolic arterial blood
      pressure. Echocardiography is very useful and powerful method for the assessment
      of morphological cardiac disorders in patients on hemodialysis.

PMID- 10934831
TI  - [Precarcinoma and early carcinomatous lesions in the uterine cervix and the use
      of oral contraceptives].
AB  - Precancerous and early cancerous lesions of the cervix uteri (ASCUS, AGUS, LSIL
      and HSIL) are precursors of invasive cancer of the cervix uteri. By Papanicolaou
      test they are graded as Pap III and Pap IV. Different factors may increase a risk
      for those lesions as well as converting low stage lesion into higher one. Oral
      contraceptive use is one of the most potential risk factor for those lesions. The
      goal of this study was to examine a relationship between oral contraceptive use
      and precancerous and early cancerous lesion of the cervix lesion of the cervix
      uteri by using Papanicolaou test. After adjustment for other potential risk
      factors our results have shown: 1) there is high significant positive
      relationship between oral contraceptives use and precancerous and early cancerous
      lesions of the cervix uteri; 2) the users of oral contraceptives have shown Pap
      III and Pap IV smear grade five to ten years earlier than non-users; 3) long-term
      users have shown Pap III and Pap IV five years earlier than short-term users for
      middle age group (35-44 years); 4) the border between Pap III and Pap IV is
      shifted for five years toward earlier age.

PMID- 10934833
TI  - The cascade concept for Doppler-cardiographic quantification.
AB  - On the basis of the presented original "cascade concept" from extrapolated
      formulas one could perform exactly the individual approximation for the left
      ventricular performance and for the diastolic cardiac function, respectively,
      according to the degree of absolute and procentual deviation from the given
      normal values excluding the influence of the body surface area (m2), the heart
      rate (min-1) and the life age (years). The Doppler-cardiographic indications for
      the left ventricular performance are the mitral filling index in the L/min/m2 and
      flow distance index in the cm/min/m2, the stroke volume in ml and flow volume in
      the L/min, the stroke distance in cm and the flow distance in the cm/min, the
      filling volume in ml/m2 and the distance index in the cm/m2, respectively.

PMID- 10934832
TI  - [Rates of stillbirths in Kuwaiti women with non-insulin-dependent diabetes].
AB  - The objective of the present study was to discern stillbirth rates in patients
      diagnosed as having NIDDM. Also, it describes sociodemographic characteristics,
      and diabetes related factors that distinguish women with established NIDDM who
      experienced repeated stillbirths from those who did not. The sample data by 99
      Kuwaiti women with NIDDM who are still in the reproduction-age are from a cross
      sectional survey carried out in 1995/96. A high prevalence of obesity,
      illiteracy, and reported physical inactivity was associated with NIDDM.
      Stillbirth rates (rate per thousand deliveries) were 76.5 in comparison to 6.9
      from general population in 1996 in Kuwait. Logistic regression analysis showed
      that housewives were less prone to stillbirths and that repeated stillbirths were
      associated with abortions. Reproduction and diabetes were mainly researched in
      patients with Type I diabetes. A high prevalence (18.1%) of NIDDM (non-insulin
      dependent diabetes mellitus) in women in Kuwait, and a younger age at diagnosis
      can have an impact on the reproduction pattern. There is a need to implement the
      appropriate interventions to reduce risk for stillbirths in women with special
      risk profiles.

PMID- 10934834
TI  - [The role of omeprazole in the eradication of Helicobacter pylori in patients
      with duodenal ulcers].
AB  - BACKGROUND: This research study has tried to establish efficiency of omeprazole,
      in combination with two antibiotics (metronidazol and amoxicilin), with the aim
      to eradicate Helicobacter pylori (H. pylori). Efficiency of omeprazole in healing
      duodenal ulcer has also been observed. PATIENTS AND METHODS: Patients suffering
      from dyspeptic problems and duodenal ulcer but positive H. pylori status (proved
      with CLO test) have been examined. Patients have been treated during the first
      seven days with triple therapy (omeprazol 2 x 20 mg, metronidazol 2 x 500 mg and
      amoksicilin 2 x 1000 mg). Subsequently, the patients were ordered omeprazole 20
      mg in the one single morning dose in period of 21 days. Control endoscopy with
      the view of establishing the rate of healing ulcer and eradicating H. pylori was
      made four weeks after the beginning of the therapy. RESULTS: Complete eradication
      of H. pylori was found with 35/43 (81.4%) patients, and alleviation of ulcer was
      achieved with 40/43 (93.1%) patients. Not a single patient had any complication
      after the beginning of treatment with omeprazole. Five patients (11.6%) had
      increased dyspeptic problems but interruption of the therapy was not required.
      CONCLUSION: Triple therapy with omeprazole, metronidazol and amoxicilin brings a
      high rate of eradication H. pylori and healing duodenal ulcer. Therapy is being
      well tolerated, the pain and dyspeptic problems are being quickly removed.

PMID- 10934835
TI  - [Acute myeloblastic leukemia and adenocarcinoma of the rectum as secondary
      malignancies after treatment of rhabdomyosarcoma].
AB  - It is shown very rare case of eight years old girl with two secondary sicknesses:
      myeloic leucosis and adenocarcinoma of rectum that developed after six years of
      successful treatment. The diagnose of embryonal Rhabdomyosarcoma was set up in
      Sarajevo six years ago after surgical extirpation of tumor from orbitae and its
      pathohistology finding. Complete chemo and radiotherapy was performed in Germany
      (Bonn) according protocol (CWS 91). Diagnoses of acute myeloic leucosis and
      adenocarcinoma of rectum was set up according: clinical picture, peripheral blood
      smear, bone marrow smear and biopsy of bleeding polyp of rectum.

PMID- 10934836
TI  - [Congenital heart defects: single ventricle with pulmonary valve stenosis and
      malposition of the great blood vessels].
AB  - A case of two: 21 years and 39 years old male patients with congenital heart
      disease: Single Ventricle with pulmonary valve stenosis and L-malposition of the
      great vessels. In the first case the diagnosis of congenital pulmonic stenosis &
      tricuspid regurgitation was established after birth and during the previous
      period. In the second case the diagnosis of VSD was established during the
      recruiting checkup, when he was 18 years old. Detailed non-invasive cardiologic
      examination was performed (transthoracic & transoesophageal echocardiography) and
      the diagnosis of Single Ventricle with pulmonary valve stenosis & L-malposition
      of the great vessels: Double-Inlet Left Ventricle with severe symptoms (21 years
      old & supraventricular paroxysmal tachycardia) with middle symptoms (39 years
      old) were established in both cases.

PMID- 10934838
TI  - [Anti-tumor drugs in the therapy of brain tumors].
AB  - In order to improve the quality of life and its duration, beside surgical
      operation with a patient with brain cancer, chemotherapy alone or in combination
      with radiotherapy may be applied in some cases. There are different protocols of
      chemotherapeutics (anticarcinomatous drugs) which are applied in treatment of
      some sorts carcinoma. The success of the therapy depends on the type and stage of
      the carcinoma, condition of patient well as of anticarcinomatous characteristics
      of the drug. Performed studies indicated that the life of the patients with
      glioblastom and astrocitom was prolonged through the application of carmustine or
      lomustine protocol of chemotherapy after x-rays. New anticarcinomatous drugs and
      new ways of application are investigated.

PMID- 10934837
TI  - [Reduced quality of life in liver cirrhosis].
AB  - BACKGROUND: Greater interest for quality of life in chronic diseases has been
      given recently. Method for examination is application of SF-36 form. In this
      study we followed changes in quality of life for patients with liver cirrhosis in
      Bosnia and Herzegovina. PATIENTS AND METHODS: 45 patients suffered from liver
      cirrhosis, 15 in class A, 15 in class B and 15 in class C according to Child,
      completed answers in form SF-36. 45 healthy control volunteers completed the same
      form. Results of score were compared to control group and to each other. RESULTS:
      Significantly reduced quality of life in physical functioning and role physical
      were in class Child A compared to control group. In class Child B significant
      decrease in score for physical functioning, general health perception and energy
      and vitality compared to Child A. In Child C 6 of 8 scores were significantly
      decreased compared to class Child B. Ascites decreased significantly score for
      quality of life in Class Child B and in class Child C portal encephalopathy
      decreased quality of life too. CONCLUSION: Health related quality of life was
      reduced in liver cirrhosis. Quality of life was reduced more in disease with more
      complications.

PMID- 10934839
TI  - [Trandolapril in the prevention of the sequelae of left ventricular systolic
      dysfunction after acute myocardial infarct].
AB  - Left ventricle systolic dysfunction and congestive heart failure after AMI are
      still a great problem in cardiology. Introduction of angiotensin converting
      enzyme (ACE) inhibitors after AMI has been a new step in therapy of the left
      ventricle systolic disfunction. Some long term studies have proved influence of
      ACE inhibitors on reduction of mortality, severe congestive heart failure (CHF),
      and reinfarction. The importance of administration of a remedy once daily has
      been emphasized, and the pharmacokinetics and pharmacodynamics of trandolapril in
      the left ventricle dysfunction and CHF has been described. TRACE study proved
      influence of long-term once daily administration of trandolapril on significant
      reduction of total and cardiovascular mortality, reduction of sudden death,
      reduction of severe and resistant CHF and reduction or relay of reinfarction. A
      good risk/benefit ratio has been found.

PMID- 10934840
TI  - [The head--the most frequently injured part of the body in traffic accidents].
AB  - In the introduction we have given the fundamental notices about the accidents and
      in their structure about the traffic's accident special as an emergency. In three
      years (1996, 1997 and 1998) we have treated 69,937 patients. Among them 579
      (0.8%) have been injured in the traffic's accident. The injuridest part of the
      body in the traffic's accident has been the head (37.6%), and the legs (17.39%),
      and the thorax (17%).

PMID- 10934841
TI  - The accuracy of C-reactive protein in the diagnosis of acute appendicitis
      compared with that of clinical diagnosis.
AB  - BACKGROUND: Acute appendicitis is one of the most common surgical emergencies.
      Its diagnosis is usually made depending on presenting history, clinical
      evaluation and laboratory tests. It has been estimated that the accuracy of the
      clinical diagnosis of acute appendicitis is lying between 76% and 92% (1).
      Negative appendectomies are one of the burdens facing not only the general
      surgeon but also the patient himself and the society as a whole, since
      appendectomy, as any other operation, results in socio-economic impacts in form
      of lost working days and declined productivity. OBJECTIVES: To determine the
      accuracy of c-reactive protein (CRP) in the diagnosis of acute appendicitis in
      comparison with the accuracy of clinical diagnosis. METHODS: This is a
      prospective study of all appendectomized patients during a one-year period in
      King Hussein Hospital in Amman/Jordan. RESULTS: A total of 98 patients were
      included in this study. The diagnosis of acute appendicitis was
      histopathologically confirmed in 89 patients (91%), while 9 normal appendixes
      (9%) were removed. The readings of CRP were ranging between 0 and 11.7 mg/l (mean
      5.6 mg/l) in patients with normal appendixes, and between 6-93.4 mg/l (mean 36.2
      mg/l) in patients with acute appendicitis. Normal CRP readings were found in 4
      patients with acute appendicitis, and of the 9 cases with normal appendectomy,
      CRP level was elevated in only one patient, so the CRP levels were true
      (positively or negatively) in 93 patients and it was false positive in one
      patient (11%) and false negative in 4 patients (4%). On the other hand, the
      clinical diagnosis was correct in 89 cases (91%) and false in 9 cases (9%), the
      difference is statistically significant (p value = 0.009). CONCLUSIONS: We
      conclude that CRP is very helpful in the diagnosis of acute appendicitis, but it
      doesn't replace the clinical skills of general surgeons.

PMID- 10934842
TI  - Discontinuation of SSRI's in traumatized refugees.
AB  - OBJECTIVE: To conduct a preliminary study on the discontinuation of SSRI's in a
      population of traumatized refugees from Bosnia. SUBJECTS: Subjects were the 33
      Bosnian refugees being treated in our clinical program who had discontinued
      SSRI's over a six month period. All had been on SSRI's for over one year and had
      shown a therapeutic response. The discontinuations were either planned with their
      clinician or self-initiated. Their age were ranged between 36 and 64, with a
      means of 56. Ten were men and twenty three were women. Standardized assessments
      were done approximately 2 months after discontinuation. RESULTS: Upon
      reassessment after discontinuation, fourteen (43%) met symptom criteria for PTSD.
      He means PTSD severity rating was 16.0 and the BDI score was 8.5. Seven persons
      (21%) restarted SSRI's and twenty-six (79%) did not. Statistical analysis showed
      that the group that restarted differed from the others in terms of lower age,
      higher PTSD diagnosis and severity, higher BDI score, poorer sleep, and higher
      subjective with either PTSD or BDI scores. CONCLUSION: This preliminary study
      suggests that when traumatized refugees discontinue SSRI's, still they have
      significant PTSD and depressive symptoms, indicating chronicity. The choice of
      discontinue or restart SSRI's is in part related to symptom severity, but other
      psychosocial factors appear entering into the equation. There is a need for
      further research.

PMID- 10934844
TI  - [Therapy of the Melkersson-Rosenthal syndrome with kenalog].
AB  - IA case of Melkersson-Rosenthal syndrome with major and minor symptoms is
      presented. Clinical diagnosis was established on the basis of the triad:
      macrocheilia, lingua plicata and facial paralysis and a number of minor symptoms.
      The upper lip macrocheilia with palpation evident infiltrates corresponded to the
      diagnosis of granulomatous cheilitis of the upper lip. The upper lip was of
      intense red color, with the vermilion border effaced causing a marked cosmetic
      defect. The predominant subjective symptoms were burning and itching sensations
      with a reduction of movement of the lip. Clinical examination and palpation
      revealed three granulations enclosed by fissures. A slight exfoliation of the
      epithelia with serous exudate was dominant feature. The patient was admitted to
      the Oral Medicine Department of Dental School in Sarajevo on October 8th 1999 for
      macrocheilia relapses. The therapy using subcutaneous application of kenalog-40
      suspension once a week in duration of five weeks showed substantial improvement.
      According to the prognostic criteria and the control examinations there were no
      relapses.

PMID- 10934843
TI  - Dental radiographic changes in chronic renal disease.
AB  - The clinical and radiological aspects of the consecutive effect of renal
      osteodystrophy on dental and alveolar were discussed in 42 patients under the
      hemodialytic treatment with 252 dental and 84 panoramic radiographs used in order
      to verify the diagnosis. It has been established that the duration with the
      increase of periodontal indices as well as with the loss of lamine dure,
      deviations within the trabecular pattern and an increase of pseudocystic
      formations as well as the calcifications in dental pulp.

PMID- 10934845
TI  - Physical therapy in conservative (functional) treatment of acute achilles tendon
      rupture.
AB  - 1. All patients returned to their daily working activities. 2. We did not record
      a single case with complications. 3. With regard to other methods of treatment
      the functional treatment is apparently without an alternative, but at the same
      time requires methods that seek full engagement of a surgeon, a radiologist and a
      physiatrist. 4. In order to avoid compromising and make the treatment successful,
      it is necessary to keep up with the implementation protocol, to have available
      adequate coeffective shoes or other means, and to possess certain level of
      clinical experience.

PMID- 10934846
TI  - [Immunological aspects of modern forms of pneumoconioses].
AB  - The authors determined pneumoconiosis as a chronic diffuse or diffuse and
      granulomatous pneumonitis with pulmonary fibrosis. The article deals with
      identification of lymphocytes subpopulations through monoclonal antibodies,
      details peculiarities of cellular immunity in pneumoconiosis patients, contains
      new data on LgE-dependent inflammatory mechanisms including specific response to
      industrial dust allergens. Discussion covers ways of immune correction therapy
      and immune prophylactics in accordance with phases of body response to homotoxins
      produced due to exogenous dust load.

PMID- 10934847
TI  - [Dynamic surface tension of blood in chronic dust bronchitis in coal mines
      workers].
AB  - Chronic dust bronchitis in miners is associated with increase in dynamic surface
      tension of blood at short (t = 0.01 s) and medium (t = 1 s) surface lifetimes
      with lower declination angle of interphase tensiograms curve. Surface tension
      disorders were similar to those in experimental dust bronchitis. There are
      correlations between surface tension parameters and the workers' underground
      length of service, some mining geologic conditions and serum level of proteous
      and lipid surfactants.

PMID- 10934848
TI  - [Health status among the staff at the nuclear waste processing plant].
AB  - Based on annual medical examinations over 20 years, the authors evaluated health
      state of stuffers (423 individuals) who work at the first Russian plant treating
      nuclear fuel waste. Over the stated time no hematologic, neurologic and other
      syndromes and diseases caused by radiation were revealed. Moderate increase in
      platelet and WBC counts appeared in first years of work (adaptive response) and
      higher parameters of bronchial obstruction in smokers. The article presents
      incidence and structure of the diseases first revealed.

PMID- 10934849
TI  - [Morbidity among the workers of the hydrolysis yeast production].
AB  - Influence of protein-containing dust on the workers results in respiratory
      diseases. Individuals working in the shops with high level of protein-containing
      dust in the air of workplace more frequently demonstrate chronic bronchitis and
      exogenous allergic alveolitis, workers of the shops with low level of the dust in
      the air of workplace more commonly suffer from bronchial asthma. The authors
      necessitate adaptation of engineering, technical and medical prophylactic means
      to lower the morbidity level.

PMID- 10934850
TI  - [Genetic factors predisposing to occupational fluorosis].
AB  - Having analyzed a total amount of all systems, the authors specified the most
      important genetic markers predisposing to chronic flour intoxication: the
      patients demonstrated higher frequency of ACP1*A and PGM1*1-alleles, phenotypes
      of acid phosphatase AA, of phosphoglucomutase 1+1+ and 2+2+, of dry cerumen
      consistence--d. The results could help to improve criteria of occupational
      selection and to specify practical recommendations on prophylaxis of chronic
      fluor intoxication.

PMID- 10934851
TI  - [Approaches to evaluation of occupational lead load in copper industry
      enterprise].
AB  - Evaluation of copper industry in Saxony revealed serum lead concentrations in 109
      workers under the allowable level accepted in Germany for workers contacting
      lead, ambient lead concentrations in air of workplace rarely 2-4 times over the
      allowable level. The authors recommend these parameters of exposure as a basis
      for evaluating health state of workers.

PMID- 10934852
TI  - [The nature of fluorosis from the viewpoint of intercellular interactions concept
      in connective tissue system (analytic review)].

PMID- 10934853
TI  - [Contemporary methods of diagnosis and monitoring of the excessive iron intake by
      humans through inhalation].
AB  - Determining iron content of target organs, blood and serum through magnetographic
      methods enables to reveal excessive intake of exogenous iron. Increased iron
      level could result in some diseases and aging, therefore the presented method
      determining iron becomes quite topical.

PMID- 10934854
TI  - [Atomic absorption in mercury determination by "Julia-2" analyzer and urine
      mercury level in children of Moscow suburbs].
AB  - The authors report on atomic absorption method determining mercury in urine.
      Being sensitive, with lower determination threshold of 10 nmole/l and correctness
      of 95.5%, the method was tested on children living in two districts of Moscow
      suburb.

PMID- 10934855
TI  - [The plane pilot's cardiovascular response to real and simulated flight
      situations].

PMID- 10934856
TI  - [Evaluation and correction of the health status in children living in the regions
      with high technological load].

PMID- 10934858
TI  - [In Process Citation]

PMID- 10934857
TI  - [Health status of female workers in the gold-mining factories].

PMID- 10934859
TI  - Deaths: final data for 1998.
AB  - OBJECTIVES: This report presents final 1998 data on U.S. deaths and death rates
      according to demographic and medical characteristics such as age, sex, race,
      Hispanic origin, marital status, educational attainment, injury at work, State of
      residence, and cause of death. Trends and patterns in general mortality, life
      expectancy, and infant and maternal mortality are also described. A previous
      report presented preliminary mortality data for 1998. METHODS: In 1998 a total of
      2,337,256 deaths were reported in the United States. This report presents
      descriptive tabulations of information reported on the death certificates. Death
      certificates are completed by funeral directors, attending physicians, medical
      examiners, and coroners. Original records are filed in the State registration
      offices. Statistical information is compiled into a national data base through
      the Vital Statistics Cooperative Program of the National Center for Health
      Statistics (NCHS), Centers for Disease Control and Prevention. RESULTS: The 1998
      age-adjusted death rate for the United States decreased to an all-time low of
      471.7 deaths per 100,000 standard population, and life expectancy at birth
      increased to a record high of 76.7 years. Of the 15 leading causes of death in
      1998, the largest decline from the previous year--9.5 percent--in age-adjusted
      death rates was for Atherosclerosis (atherosclerosis). Human immunodeficiency
      virus (HIV) infection dropped from among the 15 leading causes for the first time
      since 1987. The age-adjusted death rate for firearm injuries decreased for the
      fifth consecutive year, declining 7.4 percent between 1997 and 1998. Among all
      causes of death, age-specific death rates rose for those under 1 year but
      declined for all other age groups, although the decline for children aged 1-4
      years was not significant. The infant mortality rate was unchanged from 1997 at
      7.2 infant deaths per 1,000 live births. CONCLUSIONS: The overall improvements in
      general mortality and life expectancy in 1998 continue the long-term downward
      trend in U.S. mortality. Although unchanged from 1997, the trend in U.S. infant
      mortality is of steady declines over the past four decades.

PMID- 10934860
TI  - [Recent advance in surgical treatment for macular diseases].

PMID- 10934861
TI  - [Sclerostomy with an erbium YAG laser--the relationship with pulse energy].
AB  - PURPOSE: To investigate the optimal pulse energy to do sclerostomy with an erbium
      YAG laser. MATERIALS AND METHODS: The experiments were performed in enucleated
      porcine eyes. We changed pulse energy and examined the effects on surrounding
      tissue. RESULTS: With the increase of pulse energy, the effects of the laser
      extended to the area surrounding the laser probe. At the threshold energy for
      doing full-thickness sclerostomy, the total energy was significantly higher than
      with higher pulse energy. And with pulse energy higher than 2 mJ, the total
      energy did not show any significant change. Histopathologically, the damaged area
      around sclerostomy became larger with the increase of pulse energy. CONCLUSION:
      The optimal energy to do full-thickness sclerostomy with this system seemed to be
      2 mJ.

PMID- 10934862
TI  - [Study on collagen viscoelastic substance as an auxiliary agent in anterior
      segment surgery--ocular irritation study by replacement of the aqueous humor in
      rabbits].
AB  - PURPOSE: Collagen solution was assessed as a possible viscoelastic substance in
      anterior segment surgery, in terms of the depth of the anterior chamber and
      ocular irritation. METHODS: The depth of the anterior chamber of enucleated
      rabbit eyes was evaluated 5 minutes after injection of collagen solution. For
      ocular irritation test, the aqueous humor of rabbits was replaced with collagen
      using sodium hyaluronate (HEALON) and phosphate buffer (PB) as controls. Follow
      up clinical examinations with hand-slit-lamp-microscopy, tonometry, pachymetry,
      and specular microscopy were performed for 7 days or 28 days, and then aqueous
      humor, corneal endothelium, and eye tissues were evaluated by gel
      electrophoresis, scanning electron microscopy, and light microscopy,
      respectively. RESULTS: 2.5% to 3% collagen solution was found to be optimal for
      maintaining the depth of the anterior chamber. No significant differences in
      clinical findings such as anterior chamber and corneal thickness or in
      biochemical and histological findings were observed among collagen-, hyaluronate-
      and PB-treated groups, except for intraocular pressure which was increased in the
      hyaluronate-treated group, but not in the collagen-treated group. CONCLUSION:
      Collagen specifically prepared for this study seems to be an excellent auxiliary
      agent for anterior segment surgery, providing an appropriate anterior chamber
      with little ocular irritation.

PMID- 10934863
TI  - [Effect of antioxidants on radical-initiated peroxidation of retinal homogenate].
AB  - PURPOSE: To compare the effect of antioxidants on radical-initiated peroxidation
      of retinal homogenate. METHODS: Lipid peroxides in bovine retinal homogenate were
      induced by 5 mM FeNO3 (Fe), 25 mM 2, 2'-azobis(2,4'-dimethylvaleronitrile) (lipid
      soluble, AMVN) or 50 mM 2,2'-azobis (2-amidinoprpane) dihydrochloride (water
      soluble, AAPH) and the preventive effects of antioxidants were measured.
      Phosphatidylcholine hydroperoxide (PC-OOH) was analyzed with high performance
      liquid chromatography (HPLC) as the endpoint biomarker. RESULTS AND CONCLUSION:
      Troglitazone, an oral hypoglycemic agent, inhibited PC-OOH production by Fe and
      AMVN. Therefore, it may be effective for protecting against oxidative stress on
      the inner surface plasma membranes and subcellular organelle. Quercetin has
      radical scavenging effects on both sides of the membrane, because it prevents PC
      OOH production by AMVN or AAPH. These results demonstrate the usefulness of an in
      vitro screening test that can accurately and rapidly determine the capacity of an
      antioxidant against lipid peroxidation or oxidative stress.

PMID- 10934864
TI  - [Variables that influence visual acuity after macular hole surgery].
AB  - PURPOSE: To evaluate the variables that influence visual acuity and visual
      improvement after macular hole surgery. METHODS: Our study included 421 eyes in
      which maculor holes were successfully closed after surgery and followed up at
      least 1 year after the last surgery. Surgical techniques were conventional
      methods (Group 1: 350 eyes) with retinal pigment scalping of the macular hole
      basis added in the refractory cases (Group 2: 71 eyes). The variables used for
      the multiple regression were gender, age, preoperative visual acuity, hole stage,
      duration of symptoms, hole size, and axial length. RESULTS: The variables that
      most influenced postoperative visual acuity were as follows: Group 1: gender (r =
      -0.011, p = 0.016), age (r = -0.17, p = 0.005), preoperative visual acuity (r =
      0.51, p < 0.0001), duration of symptoms (r = -0.015, p < 0.0001), and axial
      length (r = -0.090, p = 0.045). Group 2: age (r = -0.18, p = 0.047), and
      preoperative visual acuity (r = 0.47, p < 0.0001). CONCLUSIONS: The variables
      that influenced visual acuity and visual improvement after macular hole surgery
      were common. In Group 1: gender, age, preoperative visual acuity, duration of
      symptoms, and axial length; in Group 2: age and preoperative visual acuity.

PMID- 10934865
TI  - [Typing of herpes simplex virus in patients with uveitis].
AB  - AIM: To examine the type of herpes simplex virus (HSV) in cases with uveitis.
      MATERIALS AND METHODS: Intraocular fluid specimens obtained from 3 cases with
      herpetic iridocyclitis and 6 cases with acute retinal necrosis (ARN) were
      examined by polymerase chain reaction (PCR). HSV typing was performed by the
      restriction patterns of the PCR products. Serum samples obtained from these cases
      and 33 cases with uveitis were examined by neutralization test (NT) for the
      availability of the typing of HSV. RESULTS: The restriction patterns of the PCR
      products amplified from 3 specimens of iridocyclitis revealed HSV type 1 DNA. HSV
      type 2 DNA was identified in 5 of 6 cases of ARN and HSV type 1 DNA was found in
      only one case. The results of serum NT titers correlated with the typing of the
      amplicons. CONCLUSIONS: In the cases studied, HSV type 1 was the dominant
      etiological agent in herpetic iridocyclitis, while HSV type 2 played a similar
      role in HSV-associated ARN. The examination of the serum NT may be helpful for
      the identification of the etiological types of HSV in patients with uveitis.

PMID- 10934866
TI  - [Incidence of reopening and variables that influence reopening after macular hole
      surgery].
AB  - PURPOSE: To evaluate the incidence and variables of reopening of macular holes
      after macular hole surgery. METHODS: Our study included 467 eyes in which maculor
      holes were successfully closed after surgery. Surgical techniques consisted of
      conventional methods (358 eyes) and scalping methods (109 eyes) with retinal
      pigment scalping of the macular hole basis added in such cases: reoperation, hole
      size (more than 0.4 disc diameter), duration of symptoms (more than 2 years).
      Long term incidence of reopening was predicted by life table method. After we
      compared reopened cases with non-reopened cases, the variables of gender, stage,
      biocular occurrence, age, duration of symptoms, hole size, preoperative visual
      acuity, refraction axial length ratio, and intraoperative retinal tears were used
      for the multiple regression. RESULTS: Reopening was found in 20 eyes (5.6%)
      treated by conventional methods and in 10 eyes (9.2%) treated by scalping
      methods. Survival ratio was 87% for the conventional methods in 6 years and 79%
      for the scalping methods in 5 years. The variables influencing reopening were as
      follows: conventional methods: gender (r = 0.065, p = 0.19), biocular occurrence
      (r = 0.12, p = 0.026), and refraction axial length ratio (r = -0.11, p = 0.045);
      scalping methods: hole size (r = 0.14, p = 0.25). CONCLUSIONS: Incidence of
      reopening in scalping methods was high. The variables that influenced reopening
      after macular hole surgery were biocular occurrence and refraction axial length
      ratio in conventional methods. The shape of the eye may be related to reopening.

PMID- 10934867
TI  - [Factors influencing visual acuity following vitrectomy for exudative age-related
      macular degeneration].
AB  - PURPOSE: We investigated the influence of various factors on visual results in
      patients undergoing surgical removal of choroidal neovascular membranes (CNVM)
      caused by age-related macular degeneration (AMD). SUBJECTS AND METHODS: This
      study was performed in 55 eyes of 55 patients who underwent surgical removal of
      CNVM for AMD and followed them for 6 months or more. The criterion for surgical
      eligibility was active subfoveal choroidal neovascular membrane of 0.5 or more
      disc diameter above the retinal pigment epithelium with visual acuity of 0.3 or
      worse. We investigated the influence of various factors on the logarithm of the
      minimum angle of resolution (log MAR) final visual acuity. The factors were age,
      symptom duration, preoperative log MAR visual acuity, CNVM diameter, mean
      deviation with visual field analyzer, previous laser treatment, posterior
      vitreous detachment, findings of indocyanine green angiography, operative
      complications, and recurrence of CNVM. RESULTS: Better preoperative visual
      acuity, shorter symptom duration, and smaller CNVM diameter were correlated with
      better postoperative final visual acuity. CONCLUSIONS: Surgical excision of
      subfoveal CNVM may be the better therapeutic choice in selected cases with AMD.

PMID- 10934868
TI  - [Light and electron microscopic study of the retina in a patient with congenital
      glaucoma].
AB  - PURPOSE: The morphological observation of the human retinal changes caused by
      severely elevated intraocular pressure (IOP) in congenital glaucoma. METHOD:
      Light and electron microscopy. SUBJECTS: One eye of a 15-year-old boy diagnosed
      as having congenital glaucoma was obtained after he had suffered from severe
      visual disturbance and ocular pain because of extensive elevated IOP, corneal
      leukoma, and exophthalmos. RESULTS: Ganglion cells and nerve fibers in the inner
      layer were lost and replaced by Muller cell processes. The cellular elements in
      the outer layer were regularly arranged, but these cytoplasmic organelles were
      not very well developed. Most of the cellular elements of the whole retina
      contained many dense bodies. The retinal capillaries in the nerve fiber layer
      were lost or severely damaged, but some of these in the inner plexiform layer
      were intact. In the retinal arteries and veins marked thickening of the
      adventitial tissues was observed. These tissues consisted of remarkably increased
      and irregularly arranged collagen fibers, and a few elastic fibers scattered in
      some parts. CONCLUSION: It appeared that the pathological changes in the inner
      layer of the retina were caused by ischemia. The retinal vascular abnormality was
      thought to be the result of protective reaction against the severely elevated
      IOP.

PMID- 10934869
TI  - [Intracameral and lenticular penetration of locally applied deuterium-labeled
      vitamin E in rats].
AB  - PURPOSE: To confirm the intraocular dynamics of 1% deuterium (D)-labeled alpha
      tocopherol acetate (VEA) solution. METHODS: The concentrations of D3-VEA and D3
      alpha-tocopherol (VE) derived from D3-VEA in the aqueous humor and lens were
      measured after instilling 1% D3-VEA continuously into the cul-de-sac of rat eyes
      for one and three weeks. D3-VEA and D3-VE concentrations were determined by gas
      chromatograph/mass spectrometry. RESULTS: D3-VEA and D3-VE concentrations in the
      aqueous humor after one and three weeks of continuous administration were 93.1
      and 498.9, and 9.4 and 21.5 ng/ml, respectively. The concentrations in the lens
      were 15.0 and 6.1, and 9.8 and 4.8 ng/g, respectively. CONCLUSION: The
      penetration of VEA into the aqueous humor and lens by eyedrop application was
      confirmed.

PMID- 10934870
TI  - [Recent topics of alcoholic liver disease: basic and clinical aspects].

PMID- 10934871
TI  - [Genetic alterations in human pancreatic cancer].

PMID- 10934872
TI  - [A case of gastric ascariasis removed by endoscopic procedure].

PMID- 10934873
TI  - [An operative case of gastrointestinal stromal tumor (GIST) incarcerated into
      duodenal lumen].

PMID- 10934874
TI  - [A case of duodenal gangliocytic paraganglioma].

PMID- 10934875
TI  - [A case of left-sided ulcerative colitis successfully treated with mesalazine
      enema but not steroid suppository].

PMID- 10934876
TI  - [Spontaneous pneumoperitoneum: report of a case].

PMID- 10934877
TI  - [A case of ulcerative colitis complicated by nontoxic megacolon].

PMID- 10934878
TI  - [A case of microscopic polyarteritis nodosa associated with autoimmune hepatitis
      complicated with rheumatoid arthritis and chronic thyroiditis].

PMID- 10934879
TI  - [Hyperplastic nodules of the liver (4 cm in diameter) in a patient with alcoholic
      liver cirrhosis].

PMID- 10934880
TI  - [A case of clear cell carcinoma of the hepatic bile duct with production of alpha
      fetoprotein (AFP)].

PMID- 10934881
TI  - [A case of hepatic alveolar echinococcosis with peritoneal dissemination].

PMID- 10934882
TI  - [Cutaneous and mucosal manifestations of inflammatory bowel diseases].
AB  - The rheumatological, ophthalmological- and dermatological complications are the
      most common ones among the extraintestinal manifestations of inflammatory bowel
      diseases (IBD). The incidence of skin manifestations is estimated to be 15-20% in
      case of Crohn's disease and 10% in case of ulcerative colitis. The so called
      specific lesions (perianal fissures, metastatic Crohn's disease), which are part
      of the skin symptoms associated with IBD, show a intimate connections with the
      bowel disease itself, as they histologically show granulomatous inflammation with
      epitheloid cells, similar to the ones seen in the intestines. The reactive lesion
      (erythema nodosum, pyoderma gangraenosum), that form the second main group of
      skin changes, can also be found is other systemic diseases, but they are more
      frequently associated with IBD than the average. Cutaneous manifestations may
      occur due to malabsorption or drug therapy. Finally, there are dermatoses
      (epidermolysis bullosa acquisitia, acne fulminans) which have a still
      questionable connection with IBD. Authors present an overview of the IBD's
      possible skin and mucosal symptoms and their prognostic significance and they
      demonstrate some rare common skin manifestations found among the IBD patients of
      Borsod Country (580 ulcerative colitis, 265 Crohn's disease) in the last 25
      years.

PMID- 10934883
TI  - [Various clinical patterns of relapsing polychondritis in six cases].
AB  - Relapsing polychondritis is a relatively rare disease characterized by episodic
      inflammation and progressive destruction of cartilage involving ears, nasal and
      laryngotracheal cartilage, cardiovascular system and the eyes. The increasing
      awareness of its clinically distinct has resulted in recognition of at least 550
      reported cases. Six cases are reported to demonstrate the wide variety of
      clinical pattern. The most common features of the disease are auricular and nasal
      cartilage inflammation and nondeforming arthritis. Ocular symptoms and vasculitis
      is relatively rare. Two cases of relapsing polychondritis with
      laryngotracheobronchial manifestations illustrate the severe clinical features of
      the disease. Relapsing polychondritis may associate with diverse forms of
      connective tissue disease, such as rheumatoid arthritis. It seems interesting to
      note the onset in childhood. Treatment has been primarily symptomatic. In
      situations of mild symptoms, initial treatment is with nonsteroidal
      antiinflammatory drugs. For cases with serious manifestation, corticosteroids and
      immunosuppressants are indicated.

PMID- 10934884
TI  - [Detection of minimal residual diseases in B-cell tumors using PCR specific for
      the immunoglobulin heavy chain gene].
AB  - In B-cell non-Hodgkin's lymphomas (NHL), clonal rearrangement of the
      immunoglobulin heavy chain (IgH) gene provides a useful marker for the detection
      of minimal residual disease (MRD) after treatment. To explore clinical usefulness
      of polymerase chain reaction (PCR) analysis of clonal IgH gene rearrangement in
      the detection of MRD a follow up study of 10 patients with B-cell NHL have been
      performed. At the time of diagnosis, tumor DNAs were PCR-amplified using sense
      primer specific for the heavy chain variable region (VH) and antisense primer
      specific for the heavy chain joining region (JH) of the IgH gene. The clonal
      rearrangement of IgH gene detected by PCR was used as clonal marker to determine
      MRD after treatment. In three cases, where clinical remission was not achieved,
      clonal IgH gene rearrangement was detected after the treatment. In seven cases,
      clinical remission was achieved after induction therapy but the PCR analysis
      revealed clonal IgH gene rearrangement in three of the cases. In all of the three
      cases, where MRD was detected by PCR, clinical relapse developed after 7-28
      months of the therapy. In all cases that have relapsed, the IgH gene
      rearrangement was identical at the time of initial diagnosis and at the relapse.
      This study demonstrates that PCR analysis of clonal IgH gene rearrangement is a
      useful method to monitor and detect MRD before clinical relapse.

PMID- 10934885
TI  - [Effectiveness and tolerability of the glucocorticoid mometasone furoate given as
      nasal spray in seasonal allergic rhinitis].
AB  - The clinical effect and tolerance of momethasone furoate (MF) glucocorticoid
      nasal spray (MFNS) were studied in 14-70 year-old patients suffering from
      seasonal allergic rhinitis. The patients administered daily one (morning) dose,
      100 micrograms each, of MF into both nostrils, for a period of 14 days. They did
      not use other medicines affecting nasal symptoms. Nasal symptoms (nasal
      discharge, nasal obstruction, nasal itching, sneezing) and non-nasal symptoms
      (lacrimation, eye itching/burning sensation, palatal itching, ear itching,
      general itching), scored 0 to 3, and serving as a basis for evaluating the
      effect, were registered before treatment (day 1) and at visits on 3, 7 and 14th
      day. Of the 196 patients involved in the open multicentric study, 188 completed
      the study. The total average nasal symptom scores decreased, already after 3 days
      of treatment, from 8.7 to 4.1 and to 1.6 by the 14th day. Decrease of non-nasal
      symptoms was also conspicuous, however, lacrimation persisted in 57 of 188 cases,
      while eye itching--mainly in moderate and mild form--in 90 cases. The general
      condition of rhinitis before the treatment was evaluated by the examiners as
      severe or very severe in 155 cases (82%), as symptom-free (99 cases) on day 14
      in, and mild (71 cases), in 170 cases (90%). The therapeutic effect was
      considered by both, patients and physician, as excellent, in 106 (56%) and 115
      (61%) cases, resp. and as good in 63 (34%) and 56 cases (30%). Side-effects were
      mostly mild and transitory. Treatment was not discontinued due to side-effect in
      any of the cases. Based on the results, MFNS, administered in a single daily dose
      of 200 micrograms, has proved to be an effective and safe glucocorticoid
      preparation, also easy to use locally, in the treatment of allergic rhinitis.

PMID- 10934886
TI  - [Ventricular septal defect in osteogenesis imperfecta].
AB  - A 20-year-old man with osteogenesis imperfecta type one and membranous
      ventricular septal defect is presented. The association of these two connective
      tissue abnormalities is rare. It is the first reported case in Hungary.

PMID- 10934888
TI  - [In Process Citation]

PMID- 10934887
TI  - [Some events in the course of Hungarian traumatologic surgery].

PMID- 10934889
TI  - [Medicine is a science].

PMID- 10934890
TI  - [Morphine in severe asthma attacks?].

PMID- 10934891
TI  - [Treatment of pulmonary artery hypertension].

PMID- 10934892
TI  - [efficacy and safety of salmeterol in long-term therapy in patients with chronic
      obstructive airway diseases].
AB  - BACKGROUND: Salmeterol is a long-acting inhaled beta 2-agonist with a
      bronchodilating effect lasting over 10 to 12 hours. METHODS: A prospective, open,
      multi-centre study was performed to evaluate the efficacy and safety of inhaled
      salmeterol (50 micrograms BID) over a mean treatment period of 29 months (range:
      4-1145 days) in 634 patients (54% male, age 45 +/- 15 years) with mild to
      moderate asthma or chronic obstructive pulmonary disease (COPD). Peak expiratory
      flow rates, rescue use of short acting beta 2-agonists and safety were study
      objectives. Patients were critically monitored for a possible loss of
      bronchodilator efficacy of salmeterol during long-term treatment. RESULTS: During
      the first month of salmeterol therapy, morning peak flow improved from 384 +/-
      104 l/min to 413 +/- 112 l/min (p < 0.001), and use of rescue salbutamol was
      significantly reduced (21 +/- 21 to 8 +/- 14 puffs/week during daytime and 9 +/-
      12 to 4.5 +/- 9 puffs/week during nighttime, p < 0.001 both comparisons). Peak
      flow improvement and reduction of short-acting beta 2-agonist use was maintained
      during the whole study period. Frequent adverse events were exacerbations of the
      underlying airway disease (24%) and infections (12%), while typical
      pharmacological side-effects like tremor or tachycardia where reported in less
      than 1% of all patients. CONCLUSIONS: These results confirm the persistent
      efficacy and favourable safety profile of salmeterol during long-term therapy
      over more than two years. No clinical signs of a decreasing bronchodilator
      potency indicating tachyphylaxis were observed. Salmeterol treatment provides a
      therapeutic option to further improve the management and care of patients with
      moderate obstructive airway diseases.

PMID- 10934893
TI  - [Pulmonary vasculitis. Lung support in systemic vascular deterioration].

PMID- 10934894
TI  - [Interferon alpha-2a in the treatment of diffuse thoracic angiomatosis in
      adulthood--a ase report].
AB  - A diffuse angiomatosis affecting thoracal organs is a rare, frequently fatal
      disorder occurring mainly in childhood. The definite diagnosis is usually made by
      autopsy. A specific treatment does not exist. In the case report presented here
      we describe the course of an 37-year old patient presenting initially with
      dyspnea and hemoptysis. Radiological investigations showed a mass lesion in the
      anterior superior mediastinum, bihilar masses and a periesophageal mass with soft
      tissue density and a pericardial effusion. Bilateral interstitial infiltrations
      were also present. CT-guided mediastinal biopsies and bronchial mucosal biopsies
      were nonspecific. Open-lung biopsy revealed the diagnosis of an extensive diffuse
      angiomatosis affecting mediastinum, pericardium and pleura. During the 18-month
      monotherapy with interferon-alpha 2a the patient showed significant improvements
      of clinical as well as laboratory and radiological parameters. The presented case
      confirms the experience of several authors, that the diagnosis of a diffuse
      thoracal authors can only be made by open lung biopsy or autopsy. The presented
      case also underlines the possibility of a palliative therapy of aggressive
      angiomatous diseases with interferon-alpha 2a.

PMID- 10934895
TI  - [Agenesis of the left lung in combination with a persistent left superior vena
      cava and al cor triatriatum sinister in a 77 year old man].
AB  - We report the case of a 77 year old man, who was hospitalized in the final
      stadium of his congenital disease. Following a pneumonia in the right lung the
      respirator therapy was needed. Later the patient died by a chronic right heart
      failure.

PMID- 10934896
TI  - [Acute effects of bronchodilators on lung function and dyspnea in COPD patients].

PMID- 10934897
TI  - [Inhalable corticosteroids in long-term COPD treatment. Opinions of an expert
      panel].

PMID- 10934898
TI  - A comparison of different time series techniques to analyze phasic coupling: a
      case study of cardiac and electrodermal activity.
AB  - This study examined the efficiency of different time series analysis techniques
      to extract information on the coupling of spontaneous phasic physiological
      responses. We compared four bivariate approaches, cross-spectral, cross
      covariance, cross-covariance with prewhitening, and dynamic factor analysis, in
      their ability to yield unbiased estimates of (a) shared variance, (b) covariance,
      (c) strength of relationship, and (d) interchannel time-lag in empirical and
      simulated interbeat interval-electrodermal activity (IBI-EDA) time series. All
      methods produced similar estimates of the grand-averaged IBI-EDA dynamics, but
      only the measures of covariance produced reliable and unbiased estimates of the
      interindividual distribution of IBI-EDA coupling. We conclude that the extraction
      of phasic response patterns during continuous and unrestricted experimental
      situations may considerably facilitate psychophysiological research.

PMID- 10934899
TI  - Automatic and controlled attentional processes in startle eyeblink modification:
      effects of habituation of the prepulse.
AB  - The effect of prehabituation of the prepulse on startle eyeblink modification was
      studied in two experiments. In Experiment 1, college student participants were
      either prehabituated or nonhabituated to a tone that served as a prepulse in a
      startle modification passive attention paradigm. Neither short lead interval (60
      and 120 ms) prepulse inhibition (PPI) nor long lead interval (2,000 ms) prepulse
      facilitation (PPF) was affected by the prehabituation procedure. In Experiment 2,
      participants were presented with an active attention paradigm in which one of two
      tone prepulses was attended while the other was ignored. One group was
      prehabituated to the prepulses and the other was not. Unlike the results with the
      passive paradigm in Experiment 1, prehabituation did significantly diminish
      attentional modulation of PPI and PPF. These results are consistent with the
      hypothesis that passive PPI and PPF are primarily automatic processes, whereas
      attentional modulation involves controlled cognitive processing.

PMID- 10934900
TI  - Acute changes in carbon dioxide levels alter the electroencephalogram without
      affecting cognitive function.
AB  - The partial pressure of carbon dioxide in the arterial blood (PaCO2) is usually
      tightly regulated, yet it varies among healthy people at rest (range
      approximately 32-44 mmHg) as well as within an individual during many natural
      life situations. The present study examined whether modest changes in end-tidal
      PCO2 (PETCO2; a noninvasive measure of PaCO2) affect electroencephalographic
      (EEG) activity, cognitive function, and vigilance. Nine adults were ventilated
      mechanically using a mouthpiece; respiratory rate and breath size were held
      constant while PETCO2 was set to levels that produced minimal discomfort. Despite
      discrete changes in EEG, neither acute PETCO2 increases (mean = 47 mmHg) nor
      decreases (mean = 30 mmHg) from resting levels (mean = 38 mmHg) affected
      performance on cognitive tasks, latency or amplitude of the N1, P2, or P3 event
      related potential, or alertness. Modest changes in PETCO2 may cause significant
      alterations in the EEG without disturbing cognitive function.

PMID- 10934901
TI  - The effects of caffeine on visual selective attention to color: an ERP study.
AB  - Event-related potentials were recorded from 11 subjects after ingesting caffeine
      (250 mg) or placebo. Subjects were instructed to attend selectively to stimuli
      with a specified color (red or blue) in order to react to the occurrence of a
      target within the attended category. Reaction times revealed faster responses for
      the caffeine condition, whereas no differences in strategy were observed. Color
      attention effects were identified as frontal selection positivity, occipital
      selection negativity, and N2b, whereas target detection was reflected in P3b.
      Effects of treatment were found as a more positive-going frontal P2 component in
      the caffeine condition. In addition, an interaction between attention and
      treatment could be observed on the N2b component. This pattern of results
      suggests that caffeine yields a higher overall arousal level, more profound
      processing of both attended and unattended information, and an acceleration of
      motor processes.

PMID- 10934902
TI  - Selective slow-wave sleep deprivation and time-of-night effects on cognitive
      performance upon awakening.
AB  - We evaluated the effects of selective slow-wave sleep (SWS) deprivation and time
      of-night factors on cognitive performance upon awakening. Ten normal men slept
      for 6 consecutive nights in the laboratory: 1 adaptation, 2 baseline, 2 selective
      SWS deprivation, and 1 recovery night. Cognitive performance was assessed by
      means of a Descending Subtraction Task after 2, 5, and 7.5 h of sleep. There was
      an almost complete selective SWS suppression during both deprivation nights, and
      a significant SWS rebound during the recovery sleep. Regarding cognitive
      performance, a progressive linear decrease of sleep inertia upon successive
      awakenings was found during all experimental nights except for the recovery
      night. In addition, a significant decrease of sleep inertia was observed upon the
      morning awakening of the second deprivation night for the measure of performance
      speed, and a significant increase of sleep inertia upon the morning awakening of
      the recovery night for the measure of performance accuracy. The results show that
      cognitive performance upon awakening is adversely affected by sleep depth and
      that, during the sleep-wake transition, cognitive performance accuracy is more
      impaired than performance speed.

PMID- 10934903
TI  - Magnetic brain activity evoked and induced by visually presented words and
      nonverbal stimuli.
AB  - Evoked and induced magnetic brain activity measured over the left hemisphere were
      tested for their specificity to language-related processing. Induced activity
      refers to oscillatory alterations time locked but not phase locked to the
      stimulus. Words, false font stimuli, and two types of nonverbal patterns were
      presented visually while subjects performed a nonlinguistic visual feature
      detection task. The comparison of evoked and induced brain activity around 200 ms
      after stimulus onset revealed differential sensitivity to the stimuli. The M180
      component of the evoked magnetic field was larger at the processing of words and
      false font stimuli compared with nonverbal stimuli. The induced magnetic brain
      activity in the 60-Hz band at a compatible latency range was correlated with the
      familiarity of the visual Gestalt. Sensitivity to language-specific information
      processing can be concluded if a parameter differentiates the word condition from
      the nonlexical conditions. Such a difference was observed at sensors located over
      the frontal-temporal scalp regions for induced but not evoked magnetic brain
      activity. Thus, evoked and induced magnetic brain activity revealed a
      differential sensitivity to elements of cognitive processing during the given
      task.

PMID- 10934905
TI  - An electrophysiological study of the locus of the interference effect in a
      stimulus-response compatibility paradigm.
AB  - This study investigated the locus of the interference effect in a stimulus
      response compatibility task using event-related potentials (ERPs). Ten
      participants were instructed to respond to stimulus color with the left or right
      middle finger. Red or blue arrows pointed in the same direction as the response
      hand on congruent trials and pointed in the opposite direction on incongruent
      trials. Neutral trials were red or blue horizontal bars. Reaction times (RTs) to
      incongruent stimuli were significantly longer than RTs to congruent stimuli. The
      peak latency of the P300 for incongruent stimuli was significantly longer than
      that for congruent stimuli. In addition, onset of stimulus-locked lateralized
      readiness potential (LRPs) was significantly later for incongruent stimuli than
      for congruent stimuli. However, electromyogram (EMG)-locked LRPs for incongruent
      stimuli showed incorrect preparation. These results suggest that the interference
      effect might occur at the stage in which stimulus evaluation processes and
      response-related processes overlap.

PMID- 10934904
TI  - Event-related potentials elicited during a context-free homograph task in normal
      versus schizophrenic subjects.
AB  - Thought disorder in schizophrenia may involve abnormal semantic activation or
      faulty working memory maintenance. Event-related potentials (ERPs) were recorded
      while sentences reading "THE NOUN WAS ADJECTIVE/VERB" were presented to 34
      schizophrenic and 34 control subjects. Some nouns were homographs with dominant
      and subordinate meanings. Their sentence ending presented information crucial for
      interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to
      subordinate homograph-meaning sentence endings in schizophrenia would reflect a
      semantic bias to strong associates. N400 to all endings would reflect faulty
      verbal working memory maintenance. Schizophrenic subjects showed N400 activity to
      all endings, suggesting problems in contextual maintenance independent of
      content, but slightly greater N400 activity to subordinate endings that
      correlated with the severity of psychosis. Future research should help determine
      whether a semantic activation bias in schizophrenia toward strong associates is
      reflected in ERP activity or whether this effect is overshadowed by faulty verbal
      working memory maintenance of context.

PMID- 10934906
TI  - Electrophysiological estimates of the time course of semantic and phonological
      encoding during implicit picture naming.
AB  - Two different event-related potential (ERP) components were used to investigate
      the temporal processing of semantic and phonological encoding during implicit
      picture naming. Participants were shown pictures and carried out a dual choice
      go/nogo decision based on semantic information (i.e., whether the picture was of
      an object or an animal) and phonological information (i.e., whether the picture's
      name starts with a vowel or a consonant). In addition to the already established
      lateralized readiness potential (LRP; related to response preparation), we
      introduce the N200 (presumably related to response inhibition) as a tool for
      measuring online language processing. Both, the LRP and the N200 data indicated
      that semantic processing began earlier than phonological processing. The data are
      discussed in the context of language production models. Therein, the LRP and N200
      results, taken together, favor a serial or cascaded processing model of language
      production in contrast to a parallel processing account.

PMID- 10934907
TI  - Decay time of the auditory sensory memory trace during wakefulness and REM sleep.
AB  - In a repetitive auditory stimulus sequence, deviant infrequent tones typically
      elicit a component of auditory event-related potentials termed mismatch
      negativity (MMN). The elicitation of MMN is assumed to reflect the existence of a
      memory trace of the standard stimulus that has a decay time of about 10 s and is
      strengthened by repetition of the standards. The main aim of the present study
      was to test the decay time of the sensory memory trace during rapid-eye movement
      (REM) sleep vs. wakefulness, as indexed by the MMN. Subjects were presented 10
      tone trains, separated by 3, 6, or 9 s of silence, during waking and REM sleep.
      Each train consisted of 9 standards of 1000 Hz and 1 deviant of 2000 Hz that
      occurred at position 1, 2, 4, or 6. The waking deviants elicited a frontocentral
      negativity with a scalp topography equivalent to the MMN component. During REM
      sleep, the negative component showed the same scalp distribution only for the 3-s
      intertrain interval (ITI). In this brain state, the MMN amplitude was smaller and
      decreased with prolongation of the ITI. These results suggest a weaker sensory
      memory trace formation and a premature decay time of such a memory trace during
      REM sleep as compared with wakefulness.

PMID- 10934908
TI  - On the search for the neurophysiological manifestation of recollective
      experience.
AB  - M.E. Smith (1993) obtained event-related brain potentials (ERPs) from subjects
      performing a recognition memory task using "remember" (R) and "know" (K)
      judgments, and reported observing in the ERP a "neurophysiological manifestation
      of recollective experience" as a difference between the positive waveforms
      elicited by stimuli that yielded R and K judgments. We replicated his experiment
      and examined the componential structure of the R > K effect in two ways. First,
      we found that correction for P300 latency jitter eliminated the effect reported
      by Smith. Second, the application of principal component analysis indicated that
      the positive waveform elicited by the words in the test list was a P300. These
      analyses do not support the hypothesis that there is a new component (the "memory
      evoked shift") that is a specific manifestation of recollection.

PMID- 10934909
TI  - Preparation of response force and movement direction: onset effects on the
      lateralized readiness potential.
AB  - Two experiments assessed the preparatory effects of advance information about
      response force and movement direction on the lateralized readiness potential
      (LRP). In a choice reaction time (RT) task, an imperative stimulus required an
      isometric flexion or an extension of the left or right index finger. Prior
      information about response force or about movement direction reduced RT and
      shortened the interval from the onset of the imperative stimulus up to the onset
      of the LRP. Advance information, however, about direction but not about force
      decreased the interval from LRP onset to the onset of the overt response. The
      identical pattern of results was obtained in a second experiment, in which each
      participant performed both precue conditions. The findings of both experiments
      support the notion that response force is specified before movement direction.
      These results are consistent with the view accordingly different mechanisms are
      involved in the specification of muscle force and movement direction.

PMID- 10934910
TI  - Suppression and enhancement of emotional responses to unpleasant pictures.
AB  - Despite the prominence of emotional dysfunction in psychopathology, relatively
      few experiments have explicitly studied emotion regulation in adults. The present
      study examined one type of emotion regulation: voluntary regulation of short-term
      emotional responses to unpleasant visual stimuli. In a sample of 48 college
      students, both eyeblink startle magnitude and corrugator activity were sensitive
      to experimental manipulation. Instructions to suppress negative emotion led to
      both smaller startle eyeblinks and decreased corrugator activity. Instructions to
      enhance negative emotion led to larger startle eyeblinks and increased corrugator
      activity. Several advantages of this experimental manipulation are discussed,
      including the use of both a suppress and an enhance emotion condition,
      independent measurement of initial emotion elicitation and subsequent regulation
      of that emotion, the use of a completely within-subjects design, and the use of
      naturalistic emotion regulation strategies.

PMID- 10934911
TI  - Statistical control of artifacts in dense array EEG/MEG studies.
AB  - With the advent of dense sensor arrays (64-256 channels) in
      electroencephalography and magnetoencephalography studies, the probability
      increases that some recording channels are contaminated by artifact. If all
      channels are required to be artifact free, the number of acceptable trials may be
      unacceptably low. Precise artifact screening is necessary for accurate spatial
      mapping, for current density measures, for source analysis, and for accurate
      temporal analysis based on single-trial methods. Precise screening presents a
      number of problems given the large datasets. We propose a procedure for
      statistical correction of artifacts in dense array studies (SCADS), which (1)
      detects individual channel artifacts using the recording reference, (2) detects
      global artifacts using the average reference, (3) replaces artifact-contaminated
      sensors with spherical interpolation statistically weighted on the basis of all
      sensors, and (4) computes the variance of the signal across trials to document
      the stability of the averaged waveform. Examples from 128-channel recordings and
      from numerical simulations illustrate the importance of careful artifact review
      in the avoidance of analysis errors.

PMID- 10934912
TI  - Enhancing the laboratory-to-life generalizability of cardiovascular reactivity
      using multiple occasions of measurement.
AB  - Studies examining the association between laboratory measures of stress-related
      cardiovascular (CV) reactivity and responses to psychological challenges in the
      natural environment have yielded mixed results. Frequently, single laboratory
      tasks have been used to predict responses to natural stressors on a single
      occasion of measurement. Because aggregation broadens the range of stimuli
      sampled and reduces measurement error, laboratory-to-life generalizability should
      be more easily detected when multiple predictor and criterion observations are
      used. Sixty students in a public speaking course were administered multitask
      assessments of CV reactivity during two laboratory sessions and during two in
      class public speech assignments. CV responses to the classroom speeches were
      greater among those who showed larger responses in the laboratory, and these
      associations became stronger as measures were aggregated across multiple samples
      of behavior. These results support the generalizability of CV reactivity as a
      measure of individual difference, and they help to shed light on previous
      inconsistent findings in this area.

PMID- 10934913
TI  - On the reliable assessment of cardiovascular recovery: an application of curve
      fitting techniques.
AB  - The underuse of cardiovascular recovery as an adjunct to reactivity may stem from
      a lack of research on how to assess the process reliably. We explore the test
      retest reliability of three simple, intuitive approaches to measuring recovery,
      and of a more sophisticated curve-fitting technique. Eighteen young normotensive
      subjects experienced three stressors twice each, with 10-min baseline, 3-min
      task, and 20-min recovery periods and continuous monitoring of heart rate and
      blood pressure. Reactivity showed moderate reliability, but the three simple
      approaches to measuring recovery revealed essentially none. However, the curve
      fitting approach, using a three-parameter (amount, speed, and level of recovery)
      logistic function was reliable. This approach, capturing the inherently dynamic
      process of cardiovascular recovery, may allow researchers to usefully add the
      assessment of recovery to paradigms exploring reactivity as a risk factor for
      cardiovascular disease.

PMID- 10934914
TI  - Memory for drawings in locations: spatial source memory and event-related
      potentials.
AB  - Event-related potentials (ERPs) were recorded during recognition tasks for line
      drawings (items) or for both drawings and their spatial locations (sources).
      Recognized drawings elicited more positive ERPs than new drawings. Independent of
      accuracy in the spatial judgment, the old/new effect in the source recognition
      task was larger over the prefrontal scalp, and of longer temporal duration than
      in the item recognition task, suggesting that the source memory task engaged a
      qualitatively distinct memory process. More posterior scalp sites were sensitive
      to the accuracy of the source judgment, but this effect was delayed relative to
      the difference between studied and unstudied drawings, suggesting that source
      memory processes are completed after item recognition. Similarities and
      differences between spatial source memory and memory for conjunctions of other
      stimulus attributes are discussed, together with the role of prefrontal cortex in
      memory.

PMID- 10934915
TI  - [Long-term assessment of clinical parameters in patients with coronary heart
      disease after balloon angioplasty and stenting balloon angioplasty].
AB  - The aim of this study was to assess clinical parameters in patients with coronary
      heart disease (CHD) in the late period after balloon coronary angioplasty (BCA)
      and intracoronary stenting (ICS). The study included 104 patients who underwent
      repeated coronary angiography (CA) 2-10 months after successful coronary
      angioplasty. Clinical parameters were analyzed in 2 groups comparable at the
      moment of its performance in terms of major clinical characteristics. Group 1
      comprised 51 patients following BCA and group 2 included 53 patients after ICS.
      Six months after the first procedure, repeated coronary angioplasty was performed
      in 19 (37.2%) and 6 (9.4%) patients after BCA and ICS, respectively (p < 0.05).
      Recurrent angina pectoris was observed in 42 patients from group 1 and in 25 ones
      from group 2, which was 82.3 and 47.2%, respectively (p < 0.05). Control CA
      revealed restenosis of the dilated artery in 22 (43.1%) of the 51 patients of
      group 1 and in 12 (22.6%) of the 53 patients of group 2. There were no
      differences between the groups in late postoperative bicycle ergometric and 24
      hour ECG monitoring findings. The findings have led to the conclusion that
      implantation of a stent into the coronary artery greatly prolongs the
      antiischemic effect of coronary angioplasty and reduces a need for repeated
      endovascular intervention, which appears as lower incidence rates of restenosis
      and recurrent angina as compared to routine balloon angioplasty.

PMID- 10934916
TI  - [Radiation diagnosis of interstitial lung diseases].
AB  - The authors analyzed the results of complex radiation study of 1192 patients with
      various interstitial lung diseases (ILD). An algorithm of differential diagnosis
      of diffuse and disseminated lesions of the lung was derived by using the
      findings. The X-ray morphological principle underlies the algorithm. The level of
      structural lesions of the lung and tissue reactions and the presence of granuloma
      shadows are the governing criteria for evaluating the gross structure in the
      differential diagnostic complex. Great emphasis is laid on the significance of
      computed tomography (CT), high performance CT in particular, which is becoming
      the priority radiation diagnostic technique in pulmonology. Morphofunctional
      studies, 99mTc AMA and 67Ga citrate pulmonary scintigraphy in particular, specify
      the magnitude of changes in the microcirculatory bed and the activity of
      intrathoracic lymph nodes.

PMID- 10934917
TI  - [Potentialities of ultrasound study in diagnosis of endophytic carcinoma of
      stomach].
AB  - The data of studies of 45 patients with gastric cancer are used to consider the
      potentialities of ultrasonography (USG) in the diagnosis of its endophytic forms.
      Its use in the diagnosis of "small" gastric carcinomas is evaluated. The USG
      semiotics of endophytic tumors of the stomach, including its "small" and early
      forms, is presented. The place of USG in the diagnostic algorithmic of gastric
      cancer is specified. In the authors' opinion, gastric USG along with traditional
      X-ray and endoscopic studies should take an appropriate place as it is beneficial
      in solving a great deal of differential diagnostic problems associated with the
      intramural spread of tumors.

PMID- 10934918
TI  - [Potentialities of computed tomography and ultrasound in diagnosis of hormonally
      active adrenal diseases: results of comparison CT and US with operative adn
      histological data].
AB  - The data given in the paper suggest that X-ray computed tomography (CT) is highly
      effective in detecting all types of hormonally active adrenal abnormalities. CT
      used in hormonally active adrenal diseases yielded data on major quantitative and
      qualitative (primarily densitometric) criteria that could be used in assessing
      the images of the adrenal area in these patients. Ultrasound study (USS) made at
      the first stage of topical diagnostic searches was of informative value in
      detecting adrenal tumor lesions, the technique being highly sensitive in the
      diagnosis of adrenal pheochromocytomas and adenocarcinomas, but less informative
      in the detection of hormonally active adrenocortical adenomas (aldesterone
      producing ones in particular) than CT. The diagnosis of various adrenocortical
      hyperplasies and the differentiation of hyperplastic and tumor forms of
      hypercorticoidism are a prerogative of CT that substantially supplements USS
      findings in such cases.

PMID- 10934919
TI  - [Nomenclature issues and hypertrophic Bertin's columns or renal parenchymal and
      pelvicalyceal intersections outline congruence symptom].
AB  - Analyzing the data available in the literature and examining echographic,
      urographic, and computed tomographic findings in 153 patients having various
      types of the doubled pelvicalycus and other structures of the kidney have led to
      the conclusion that it is more correct to use term "renal parenchymal
      intersections" rather than that "Bertin's column hypertrophy" since they are a
      variant of the anatomic structure of the renal parenchyma. The renal parenchymal
      and pelvicalyceal intersections outline congruence symptom, which was first noted
      while comparing echo- and urographic data and studying computed tomographic
      contrast-enhanced images, may be helpful in the differential diagnosis of the
      intersections with renal tumors.

PMID- 10934920
TI  - [Small pelvic MRI on "Ellipse" low-adz tomograph made in Russia].
AB  - The paper presents the authors' experience in using small pelvic MRI on an
      Ellipse low-field apparatus made in Russia. A total of 74 patients were examined.
      Abnormal formations in the small pelvic organs were visualized in 72 patients.
      The potentialities and limitations of MRI in visualizing small pelvic organs and
      their pathology are shown. The technique is compared with CT and ultrasound
      study.

PMID- 10934921
TI  - [Case of cervical spinal cord neurofibroma in patients with Recklinghausen's
      disease].

PMID- 10934922
TI  - [Radiation and instrumental diagnosis of breast diseases at the turn of centuries
      in the Russian Radiology Research Center].

PMID- 10934923
TI  - [Endovascular prevention of pulmonary thromboembolism: the state-of-art in the
      use of cava-filters (review of literature)].

PMID- 10934924
TI  - [Radiation diagnosis of biliary system befor laparoscopic cholecystectomy (review
      of literature). Part 1: ultrasonic techniques].

PMID- 10934925
TI  - Significance of de-novo IgD and IgM synthesis in CSF of patients with relapsing
      remitting form of disseminated demyelinating disease of CNS.
AB  - Disseminated demyelinating disease of the central nervous system (DDD CNS) is
      immunologically mediated, with confirmed significant intrathecal immunoglobulin
      production. According to recently known immunopathogenic occurrences and
      activation of humoral immune response, we have assumed that the presence of
      oligoclonal immunoglobulins of M and D classes can be confirmed in cerebrospinal
      fluid (CSF) of patients with DDD CNS. With the aim of its further determination
      in CSF of relapsing-remitting DDD CNS patients in either remission and relapse
      phase, respectively, we have confirmed the presence of oligoclonal IgD and IgM
      bands, the association of this production and the presence of new demyelinating
      zones found by MRI of endocranium, as the time elapsed from the last relapse
      until the obtaining of CSF for further analyses. Method of isoelectric focusing
      with Western blott procedure was used for the confirmation of oligoclonal IgM and
      IgD bands presence in CSF. Significant presence of intrathecally synthetized
      oligoclonal IgM and IgD in patients with DDD CNS in exacerbation phase was
      presented. Almost in all patients in this phase was found at least one indicator
      of acute phase (positive MRI finding, presence of oligoclonal IgM or IgD bands).
      Significant decrease of positive findings of oligoclonal Ig bands in CSF was
      correlated with the time elapsed from the onset of relapse until the obtaining of
      CSF for the analysis due to short half-life of those Ig in CSF.

PMID- 10934926
TI  - The significance of determination of the fraction of creatinine-phosphokinase in
      patients with acute ischemic brain disease.
AB  - Heart and brain vascular diseases are the leading causes of mortality in the
      world. Cardiac complications can frequently occur during the development of
      cerebral ischemia. The aim of this study was to establish the possible changes in
      fractions of creatinine-phosphokinase as the sensitive laboratory index of
      parenchymal lesion of brain parenchyma and the presence/absence of risk factors
      for ischemic brain and heart disease. The study comprised 80 patients with acute
      ischemic brain disease (AIBD), without the history of previous coronary disease.
      Blood samples were taken in all patients within the first 48 hours from AIBD
      onset aiming to determine a total (muscular MM) and heart fraction of creatinine
      phosphokinase (MB), and brain parenchyma ischemia was confirmed by CT or MR scan
      of the head. A detailed history of the risk factors for ischemic brain disease
      (IBD) and ischemic heart disease was taken from all patients with AIBD, and the
      profile of glycemia and lipid status were determined, and blood pressure was
      measured 6 times a day. Independent variables in statistical analysis were: age,
      degree of severity and the side of neurologic event, size of ischemic lesion and
      maximal values of systolic and dyastolic pressure. Dependent variables were the
      values of fractions of creatinine-phosphokinase (CPK). Control group (n = 40)
      comprised patients with neurologic diseases of non-vascular origin. All
      parameters as well as their interrelations were statistically analyzed. The
      results revealed significant correlation of the increased levels of CPK of MM and
      MB fraction with the size and place of ischemic lesion in the right cerebral
      hemisphere, which was highly significant for MB fraction in the total group of
      patients with AIBD, and for MM fraction, only for cases of more severe IBD.
      Highly significant increased values of those fractions were also observed
      compared to the control group of patients.

PMID- 10934927
TI  - [Vascularized fibular grafts in the reconstruction of bone defects caused by war
      injuries].
AB  - The efficiency of the vascularized fibular graft application in the
      reconstruction of diaphyseal defects of the long bone of extremities caused by
      war injuries was prospectively investigated in the group of 33 patients in the
      period 1991-1996, during the war in the former Yugoslavia. The preoperative,
      intraoperative and postoperative procedures were systematized. Early and late
      complications in donor and recipient regions were shown. The primary success was
      63.6% and the total one was 93.9%. The efficiency of the vascularized fibular
      graft in the treatment of bone defects caused by war injuries could be compared
      with bone defects caused by trauma or by resection of malignant tumors.

PMID- 10934928
TI  - [Reconstructive methods in the treatment of soft tissue defects below the knee].
AB  - The specificity of the lower leg is in sparse collateral blood flow of the skin
      cover in the middle and distal part, reduced subcutaneous tissue and the
      prominence of the front side of tibia immediately under the skin. These
      characteristics of the lower leg make the application of the standard plastic
      reconstructive principles, which have been applied in the other regions of the
      body to a certain degree impossible. The progress of anatomical knowledge in
      relation to vascularization of the tissue territories--angiosoma, and the anatomy
      of the vascular skin system of the lower leg, along with the technological
      progress represented by the application of the surgical microscope, new surgical
      instruments and suture materials, provides the reconstructive surgeon, not only
      with classic but also with the modern surgical methods in this region:
      microvascular transplantation of the tissue and the application of the
      fasciocutaneous reversible flaps. The aim of this study was to show the available
      reconstructive methods in the treatment of the lower leg soft tissue and to
      analyze its application in the management of war wounds in the injured from the
      civil war in the former Yugoslavia. On the basis of our experiences in the
      management of war wounds, especially of the lower leg with the tissue defects, we
      would like to point on the existence of the clear indications for the application
      of certain reconstructive methods depending on the size, localization and tissue
      defect structure, as well as the advantages and disadvantages of the available
      reconstructive procedures.

PMID- 10934929
TI  - [Surgical treatment of hypophyseal adenoma using the pterional approach].
AB  - The results of a retrospective study of 21 patients undergoing surgery with
      pterional approach to pituitary adenomas are reported. There were 7 females, and
      14 males, between 20 to 68 (average 43.5) years of age. According to adenoma
      extension 6 patients were with type III-A (suprasellar-suprachiasmatic), 4 with
      type III-B (suprasellar-retrosellar), 6 with type III-C (parasellar-cavernous),
      and 5 with type III-D (paninvasive). According to adenoma size there was 1
      patient with small (5 mm-2 cm), 11 with moderate (2-4 cm), 4 with large (4-6 cm),
      and 5 patients with paninvasive adenomas. Histopathological examination showed
      null cell in 11, growth-cell in 6, prolactin-cell in 1, and plurihormonal
      adenomas in 3 cases. Two patients have died. The cause of death was hypothalamic
      lesion or cerebral infarct.

PMID- 10934930
TI  - [Total intravenous anesthesia with propofol with midazolam coinduction--the
      anesthesia of choice in cataract surgery].
AB  - Comparative clinical investigation was performed in 80 ASA I/II patients
      undergoing cataract surgery on one eye. Patients were randomly divided in to four
      groups, according to the method of anesthesia. Intraoperatively (T0-T6),
      decreasing of intraocular pressure (IOP) to the optimal values at the start of
      the operation (T3), and the hemodynamic stability of patients after the induction
      (T1) were evaluated. Postoperatively, the recovery rate, and the incidence of
      vomiting were measured. Optimal decreasing of IOP was noticed in the second group
      (75% of patients). Best hemodynamic stability was observed in the second group
      (80% patients). Fast recovery rate was noticed in the first and the second groups
      (13.9 +/- 1.1 and 14.4 +/- 0.8 min). Vomiting was noticed in 5% patients in the
      first group, 15% in the third group, and in 20% in the 4th group. The authors
      have concluded that TIVA fourth propofol and coinduction with midazolam is
      anesthesia of choice in the cataract surgery.

PMID- 10934932
TI  - [Age as a suicide risk factor].
AB  - The aim of the paper was to determine the influence of age in suicidal occurrence
      and behavior. The subjects were the individuals who attempted or committed
      suicide in the city of Kragujevac during the observed period. We used the data
      from the Police of Serbia (Kragujevac) obtained at the scene of suicide, medical
      records, and data from the Psychiatry Center of the Clinical Center "Kragujevac".
      The data were collected and statistically evaluated by SPSS for Windows, and the
      significance was determined by chi 2 and t-test, and expressed as a rate per
      100,000 inhabitants. The greatest suicide rates were recorded in the groups of >
      or = 65 years old (27.3 per 100,000 inhabitants) and 45-54 years old (27.2 per
      100,000 inhabitants). The group of individuals > or = 45 years old was almost
      twice as inclined to suicide compared to the other except, while the youngest age
      group that showed almost equal numbers. There were more attempts (65.6%) within
      the group of 25-34 years old individuals (the same was true for the group of 35
      44 years old individuals). No differences were observed between the indigenes and
      the migrants among older suicides (> or = 55 years old). The most affected were
      the migrant 25-34 and 45-54 years old, and the indigenes 25-34 and 35-44 years
      old. Number of suicides decreased, showsed stagnation, or reached the plateau in
      all age groups (mostly), except for those 15-24 years old, during the period of
      observation the (1991-1995). The lowest figure (9.1%) was found in 1992, and than
      it increased and reached 39.4% in 1995. Furthermore, unemployed individuals 55-64
      and 15-24 years old and the employed 25-34 years old were considerably affected.
      In younger individuals, the motive--cause was unrequited love, family conflicts,
      abstinencial crisis, etc. In those a little older (24-34 years old) it was
      represented by family problems and illness (27.3%); this was also true for the
      others.

PMID- 10934931
TI  - [Analysis of the results of mycological examination of skin samples from 1997 to
      1998].
AB  - Mycological findings of 2,447 skin specimens were analyzed. The aim of the study
      was to estimate the methodology for mycological examination, frequency of
      particular fungal species isolation and localization on the skin. Fungi were
      found in 591 specimens: 53.64% microscopically and isolated in cultures, 31.47%
      only microscopically and 14.89% only isolated in cultures. Total number of
      isolated strains was 405 (356 strains grew on Sabouraud agar with antibiotics and
      272 on mycobiotic agar). The most frequently isolated species were: Trichophyton
      mentagrophytes (27.9%), Trichophyton rubrum (20%) and Candida albicans (9.14%).
      The most frequent localizations on skin where fungi had been found were foot
      (41.47%), toe-nail (22.06%) and finger-nail (10.88%). Sabouraud agar is more
      reliable for isolation of dermatophytes and mycobiotic agar for Candida species.
      Usage of both media for primoisolation provides better and faster identification
      of fungi causing dermatomycoses. Comparing our with other studies, the patterns
      of fungal appearance in our population had changed and the number of nail
      specimens, where fungi were found had increased.

PMID- 10934934
TI  - [Motor neuron disease: primary lateral sclerosis and amyotrophic lateral
      sclerosis].
AB  - AIM: Primary lateral sclerosis and amyotrophic lateral sclerosis are amongst
      motor neuron diseases. Differences between these two disorders are stressed by
      this paper. SOURCE OF DATA: Articles pertinent to this subject from the past 10
      years. CONCLUSION: Both disorders are of neurodegenerative pathogenesis, and
      motor neurons are selectively involved. Unless only motor neurons from central
      nervous system are involved in primary lateral sclerosis, in amyotrophic lateral
      sclerosis motor neurons are involved both in central and in peripheral nervous
      system. Clinical neurophysiological and radiological features are helpful in
      differential diagnosis of these diseases. Primary lateral sclerosis has better
      prognosis and much higher survival rate.

PMID- 10934933
TI  - [Post-transfusion graft vs host disease and its prevention].

PMID- 10934935
TI  - [Hemostasis and atherosclerosis].

PMID- 10934936
TI  - [Cytomegalovirus retinitis and the acquired immunodeficiency syndrome].

PMID- 10934937
TI  - [Successful surgical treatment of a massive pulmonary embolism in the organized
      thromboembolic phase].
AB  - A patient, male, aged 36, clinically presented as an unstable angina pectoris
      following myocardial infarction, who came from general hospital of Banja Luka for
      further examination is presented. According to the medical report, he was treated
      for acute myocardial infarction in 1994 at Banja Luka's general hospital, when he
      was resusciated due to of cardiac arrest. The anginous pain was still present
      regardless of prescribed therapy. Following the clinical examination at the
      Military Medical Academy we have established a diagnosis of thromboembolism of
      the main pulmonary artery with a high pressure in the right ventricle. He
      underwent surgery under the extracorporeal circulation, when an organized old
      thrombus the main pulmonary artery and partially in arterial branches. The main
      pulmonary artery was almost completely obliterated. Thrombectomy was done.
      Following the operation, the patient was in a good condition and the repeated
      echocardiographic examinations showed no signs of recurrent thrombosis while the
      pressure in the right ventricle was significantly decreased. Afterwards, he was
      treated by heparine and oral anticoagulants and then by antiagregants. This case
      is very instructive because the massive pulmonary thromboembolism which was
      wrongly recognized and treated as an acute myocardial infarction.

PMID- 10934938
TI  - [Traumatic rupture of the left hemidiaphragm].
AB  - A case of blunt traumatic rupture of the left hemidiaphragm following a traffic
      accident was presented. On admission the patient complained of a dyspnoea, and
      the physical examination of the thorax revealed the absence of breathing sound on
      the left side. A chest radiography and CT scan had shown the presence of the
      stomach in the left hemithorax. Posterolateral thoracotomy was performed. In the
      opened hemithorax, the stomach, omentum and small bowel were found to having
      passed undamaged through a 12 cm tear of the central part of the diaphragm. These
      abdominal viscera were replaced in the abdomen and the diaphragm was sutured.

PMID- 10934939
TI  - [Treatment of chronic viral hepatitis B in secondary membranoproliferative
      glomerulonephritis using recombinant alfa-2 interferon].
AB  - A patient suffering from viral hepatitis B and secondary membranoproliferative
      glomerulonephritis was presented. He was treated with recombinant alfa-2
      interferon. The therapy led to clinical and biochemical remission of the liver
      and kidney lesions. The example of our patient justifies the use of recombinant
      alfa-2 interferon in the patients with chronic viral hepatitis B and secondary
      glomerulonephritis.

PMID- 10934940
TI  - Quality assurance and risk reduction guidelines.
AB  - Cervical cancer continues to be a major cause of death in women worldwide. The
      major problem facing most women is the unavailability of screening Pap tests in
      poor and underdeveloped countries. While rates of cancer deaths have decreased 60
      80% in developed countries since the Pap test became available, the accuracy of
      Paps was challenged recently. In order to instill public confidence and promote
      optimal patient care, measures to improve the quality of the entire screening
      process should be undertaken. Continuous quality improvement processes are more
      appropriate than traditional quality assurance monitors. Although no standards
      can be defined that are applicable to all laboratory settings and nations, this
      document provides current views on universal quality procedures and risk
      reduction. Procedure/policy manuals, workload assessment, hierarchic/peer review,
      discrepancy analysis, rescreening studies and cytohistologic correlation are
      examples of universally applicable quality tools. The variability in practices in
      different parts of the world is also discussed.

PMID- 10934941
TI  - Fine needle aspiration cytology in xanthogranulomatous cholecystitis, gallbladder
      adenocarcinoma and coexistent lesions.
AB  - OBJECTIVE: To evaluate the diagnostic efficacy of fine needle aspiration cytology
      (FNAC) in gallbladder mass lesions and to explore the possibility of overlooking
      malignancy in coexistent adenocarcinoma with xanthogranulomatous cholecystitis
      (XGC) on fine needle aspiration smears. STUDY DESIGN: In a retrospective, seven
      year study, ultrasound-guided needle aspirates from 25 histologically proven
      cases of gallbladder adenocarcinoma, 11 cases of gallbladder adenocarcinoma
      associated with XGC and 20 cases of XGC were evaluated for the presence of
      mesotheliumlike, foam, inflammatory and multinucleate giant cells; pink, granular
      background; bile; and degenerated cells, along with atypical or frankly malignant
      cells. Detailed clinical findings were retrieved from the records. RESULTS: The
      overall sensitivity of detecting carcinoma was 90.63% and specificity 94.74%. The
      sensitivity of detecting malignancy was 80% when adenocarcinoma was associated
      with XGC. CONCLUSION: FNAC plays an important role in making the preoperative
      diagnosis of adenocarcinoma, XGC and coexistent lesions. The probability of
      detecting malignancy is greater than with XGC in coexistent lesions. Thus, a
      preoperative FNAC diagnosis would help in determining the urgency of treatment
      and in planning for the surgical procedure in gallbladder lesions.

PMID- 10934942
TI  - Accuracy of cytology vs. microbiopsy for the diagnosis of well-differentiated
      hepatocellular carcinoma and macroregenerative nodule. Definition of standardized
      criteria from a study of 100 cases.
AB  - OBJECTIVE: To determine the accuracy of ultrasound (US)-guided fine needle
      aspiration (FNA) for the diagnosis of well-differentiated hepatocellular
      carcinoma (wd HCC) and macroregenerative nodule (MRN) and to identify the most
      useful cytologic and histologic criteria to distinguish between those two
      diagnoses. STUDY DESIGN: Cytologic and histologic specimens of 50 wd HCC and 50
      MRN were reviewed blindly and the diagnosis compared to the final clinical
      diagnosis. Twenty-eight cytologic and 25 histologic criteria were examined and
      subjected to statistical analysis. RESULTS: Among 100 cases studied, the final
      diagnosis was available for 43. In those 43 cases, combining analysis of
      cytologic and histologic specimens, the sensitivity of US-guided FNA was of 75%
      and the specificity 100%. Cytologic analysis was better than isolated histologic
      analysis, with a sensitivity of 75% vs. 68%, respectively. Sensitivity of
      cytologic diagnosis was lower for smaller nodules and for those located in poorly
      accessible hepatic segments. With the use of stepwise logistic regression
      analysis, four cytologic features (increased nuclear/cytoplasmic ratio, cellular
      monomorphism, nuclear crowding, loss of bile duct cells) and four histologic
      features (increased nuclear/cytoplasmic ratio, decreased Kupffer cells, cellular
      monomorphism, increased trabeculae thickness) were identified as predictive of
      HCC.

PMID- 10934943
TI  - Rhabdomyosarcoma. Cytomorphology, subtyping and differential diagnostic dilemmas.
AB  - OBJECTIVE: To identify morphologic characteristics and architectural patterns of
      rhabdomyosarcoma (RMS), to attempt a subclassification from fine needle
      aspiration biopsy (FNAB) smears and to point out some differential diagnostic
      problems. STUDY DESIGN: We reviewed all positive cytologic material from 53
      patients with RMS whose diagnoses were histologically and/or immunocytochemically
      confirmed. We analyzed several morphologic features and identified architectural
      patterns of smears. RESULTS: Among alveolar RMS, we identified two major
      architectural patterns: one containing completely dissociated cells and one
      containing many chance formations. Among the embryonal type, the predominant
      architectural pattern contained large tissue fragments with abundant eosinophilic
      material and various numbers of dissociated cells. The pattern of only
      dissociated cells was similar to the one seen in the alveolar type. The relative
      proportion of poorly to better and well-differentiated rhabdomyoblasts varied in
      both types and in all patterns. CONCLUSION: RMS exhibits a variety of morphologic
      pictures regarding cellular morphology and architectural patterns, even within
      the same histologic subtype. Therefore, a reliable subclassification into
      alveolar and embryonal RMS cannot be made from FNAB smears. The embryonal type
      can be suggested in cases containing large tissue fragments with abundant
      eosinophilic material and small, tightly packed cells with oval nuclei. However,
      all cases suspected to be RMS must always be confirmed immunocytochemically since
      they could be confused with some benign and malignant tumors with similar
      morphology.

PMID- 10934944
TI  - Biliary tract brush cytology.
AB  - OBJECTIVE: To prospectively review brush smears obtained during endoscopic
      retrograde cholangiopancreatography (ERCP) primarily from the biliary tree. STUDY
      DESIGN: A total of 175 specimens from 147 patients were included in the study.
      The smears, prepared directly from the endoscopic brush, were stained by the
      Papanicolaou technique and analyzed for standard cytologic features. RESULTS: The
      smears were categorized into benign/reactive, significant atypia and
      suspicious/positive. The consistent features seen in suspicious or positive
      smears were tightly cohesive, small, three-dimensional cell clusters that formed
      cell balls. The cells in the clusters displayed features of malignant cells.
      CONCLUSION: ERCP-guided brushing is a safe diagnostic procedure for the
      evaluation of biliary tree lesions. Small, three-dimensional epithelial clusters
      with marked atypia signify malignancy and warrant the diagnosis of a malignant
      neoplasm even when only one or two such clusters are seen in the smears. Single
      cells, cytoplasmic vacuoles and prominent nucleoli are not essential for a
      diagnosis of malignancy.

PMID- 10934945
TI  - Immunocytochemical study of malignant lymphoma in serous effusions.
AB  - OBJECTIVE: To cytologically evaluate a large series of serous effusions
      associated with malignant lymphoma (ML), identify the immunoreaction patterns of
      the cells from selected positive cases and to investigate the correlation of
      cytomorphology with tissue section diagnosis. STUDY DESIGN: From 1966 to 1990, a
      review of the files of the Department of Anatomic Pathology, A. C. Camargo
      Hospital, disclosed 4,297 cases of serous effusions, 256 of which were associated
      with ML. Cytopathologically positive cases were selected for immunocytochemical
      study. All paraffin sections stained with hematoxylin and eosin were reviewed to
      confirm the malignancy of the cases. Immunostaining was performed on both
      cytocentrifuge slides previously stained with Papanicolaou stain and new sections
      of the biopsy samples using the immunoperoxidase method and avidin-biotin complex
      with monoclonal mouse antihuman B-cell marker L-26 and monoclonal (mouse)
      antihuman T-cell marker UCHL-1. RESULTS: Immunocytochemical reactions were
      performed in 54 cases: 22 were pan-B positive and 10 pan-T positive; 24 cases
      showed no reactivity for either monoclonal antibody. Immunohistochemical
      reactions were performed in 24 available cases: 15 were pan-B positive and pan-T
      positive; 3 cases showed no reactivity for either monoclonal antibody.
      Cytohistoimmunoreactions were similar in 11 pan-B positive cases and 2 pan-T
      positive cases. Three cases were negative for both markers, 4 cases were pan-T
      positive in tissue samples and negative in cytocentrifuge smears, 3 cases were
      pan-B positive in tissue and negative on cytology and 3 cases were negative for
      both markers in both tissue and cytologic specimens. CONCLUSION: Cytology is an
      effective method of evaluating serous effusions associated with malignant
      lymphoma: no false positive diagnosis was observed in this series.
      Immunophenotyping of lymphoid cells is useful to classify and confirm the
      cytologic diagnosis.

PMID- 10934946
TI  - Bull's eye (target) inclusions in neoplastic cells in malignant serous effusions.
      A study of 289 cases.
AB  - OBJECTIVE: To study the prevalence and significance of bull's eye (target)
      inclusions in neoplastic cells in malignant serous effusions. STUDY DESIGN: We
      reviewed malignant pleural, peritoneal and pericardial effusions from 289
      patients who had proven cancer at known primary sites. The ages of the patients
      ranged from 5 to 72 years; 166 were male and 123 female. RESULTS: Bull's eye
      inclusions are an uncommon finding and appeared in only 13 cases of metastatic
      adenocarcinoma of the breast, stomach, colon, lung, ovary, pancreas and urinary
      bladder. They were positively stained with periodic acid-Schiff stain with
      diastase. The inclusions were not seen in cells of nonadenocarcinomatous
      neoplasms, such as squamous cell carcinoma, oat cell (small cell) carcinoma,
      neuroblastoma, lymphoma and germ cell tumors. CONCLUSION: Bull's eye inclusions
      are found in about 5% of malignant serous effusions containing cells of
      metastatic adenocarcinoma. The primary site of an adenocarcinoma cannot be
      deduced on the basis of the presence of inclusions.

PMID- 10934947
TI  - Characterizing "blue blobs". Immunohistochemical staining and ultrastructural
      study.
AB  - OBJECTIVE: To investigate the nature and origin of "blue blobs" (Bbs) in atrophic
      Pap smears in postmenopausal women and to study their clinical significance.
      STUDY DESIGN: A retrospective study of 412 atrophic Pap smears from
      postmenopausal women was done to detect the presence of Bbs. The smears from 24
      cases showing Bbs were further studied to evaluate the nature of the Bbs with
      special stains, immunohistochemistry and electron microscopy. RESULTS: Bbs showed
      a heterogeneous morphology, with variable numbers and staining intensity. The
      diameter of Bbs was approximately equivalent to that of a parabasal/intermediate
      squamous cell. Special stains showed Bbs to be positive for periodic acid-Schiff
      and methyl green pyronin and negative for mucicarmine and calcium.
      Immunohistochemistry revealed Bbs to be positive for cytokeratin, epithelial
      membrane antigen and carcinoembryonic antigen and negative for vimentin and
      muscle-specific actin. Some Bbs had residual ghost nuclear shadows. Electron
      microscopy revealed cellular skeletons with residual tonofilaments enmeshed
      within a loose cytoskeleton matrix and nuclei with variable degrees of
      degeneration. CONCLUSION: Special stains, immunohistochemistry and electron
      microscopy indicated that Bbs represent parabasal/intermediate squamous cells
      exhibiting various degree of degeneration. In general, Bbs appear to be of no
      clinical significance except as a source of potential diagnostic error.

PMID- 10934948
TI  - Glassy cell carcinoma of the uterine cervix. Cytologic features and expression of
      estrogen and progesterone receptors.
AB  - OBJECTIVE: To identify the cytomorphologic features and investigate the
      expression of estrogen receptor (ER) and progesterone receptor (PR) in glassy
      cell carcinoma (GCC) of the uterine cervix. STUDY DESIGN: A retrospective
      analysis of nine GCCs encountered at Korea Cancer Center Hospital between January
      1990 and April 1999 was undertaken. The cervical smears were obtained prior to
      histologic diagnosis of GCC. The cytomorphologic and clinical features were
      reviewed, and the expression of ER and PR was investigated immunohistochemically
      on histologic sections. RESULTS: Smears of GCC were hypercellular and remarkably
      cohesive. The tumor cells were large and characterized by abundant granular
      cytoplasm, distinct cell membranes and round to polygonal, large nuclei with
      prominent nucleoli. In the background tumor diathesis and numerous inflammatory
      cells containing eosinophils were present. The inflammatory cells (mainly
      eosinophils) were intimately associated with tumor cells to form
      "granuloepithelial complex." Immunohistochemically, ER was identified in two of
      the nine cases and PR in one of them. CONCLUSION: Cytology of GCC has
      characteristic features that differ from those of other carcinomas or atypical
      reparative cells. Although there are deceptive mimics of GCC, the characteristic
      cytologic findings should prompt a diagnosis of GCC. ER and PR positivity was
      found in two cases (22%) and one case (11%), respectively, of GCC, suggesting
      that this tumor might be hormonally responsive.

PMID- 10934949
TI  - Clinical significance of atypical glandular cells of undetermined significance. A
      follow-up study from an academic medical center.
AB  - OBJECTIVE: To determine the rate of atypical glandular cells of undetermined
      significance (AGUS) and the incidence of subsequent clinically significant
      lesions. STUDY DESIGN: A computer-based search of our cytology laboratory files
      was performed for cervicovaginal smears diagnosed as AGUS from January 1996 to
      December 1996. RESULTS: In 43,456 cervicovaginal smears examined during the 12
      month period, AGUS was reported in 222 (0.5%) cases, with follow-up in 191
      (86.0%) (133 [59.9%] biopsies and 58 [26.1%] repeat cervicovaginal smears). Among
      the patients with repeat cervicovaginal smears, 1 (1.7%) had a high grade
      squamous intraepithelial lesion, and 10 (17.2%) had persistent AGUS/atypical
      squamous cells of undetermined significance; the remainder were within normal
      limits. Thirty-three (24.8%) patients had preneoplastic or neoplastic, squamous
      or glandular lesions on biopsy (8 [6.0%] cervical intraepithelial neoplasia [CIN]
      1, 18 [13.5%] CIN 2/3 and 7 [5.3%] endometrial adenocarcinomas). Half the
      patients with CIN 2/3 also had evidence of endocervical gland involvement.
      Squamous lesions were seen more commonly in premenopausal women, while glandular
      lesions were noted predominantly in postmenopausal women. Patients with a prior
      abnormal gynecologic history or a concomitant diagnosis of squamous
      intraepithelial lesion (SIL) had a higher incidence of significant lesions on
      subsequent biopsy. CONCLUSION: Our incidence of AGUS was 0.5%, similar to that in
      other published reports. AGUS is associated with a significant number of squamous
      or glandular, premalignant or malignant lesions. A majority of these lesions are
      high grade SIL, often with endocervical gland involvement. A small but
      significant number of patients had a glandular malignancy. Our results justify
      close and persistent follow-up for patients with a diagnosis of AGUS on
      cervicovaginal smears.

PMID- 10934950
TI  - Comparison of TriPath thin-layer technology with conventional methods on
      nongynecologic specimens.
AB  - OBJECTIVE: To evaluate the use of the TriPath PREP (previously called AutoCyte)
      TriPath Inc., Burlington, North Carolina, U.S.A.) in nongynecologic cytologic
      material by performing side-by-side comparison of conventional preparations with
      TriPath-prepared slides. STUDY DESIGN: An initial study of 613 cases (set A) was
      conducted to compare the TriPath PREP system with conventional methods for the
      evaluation of nongynecologic specimens, including urine, body cavity effusions,
      cerebrospinal fluid, pulmonary and gastrointestinal specimens. Paired cases were
      evaluated for cellularity, staining quality, preservation and representation of
      diagnostic material. Subsequent changes in the automated technique warranted
      reevaluation of the TriPath method. The follow-up study of 259 cases (set B) was
      conducted with the same design as set A. Results of evaluated parameters were
      analyzed using the chi 2 test. RESULTS: Results of the two sets were strikingly
      different. Prior to technical changes made by the laboratory, the TriPath method
      was significantly inferior. In the second set, the preferred material was most
      commonly the TriPath-prepared material. In particular, the majority of urine
      samples were prepared better by the automated, thin-layer system. CONCLUSION: The
      TriPath PREP system offers a reliable preparation of urine and has potential for
      other nongynecologic specimens, provided that careful attention is paid to
      technical details and some adjustments are made to account for specimen
      variability.

PMID- 10934951
TI  - Cytologic predictors of cervical intraepithelial neoplasia in women with an ASCUS
      Pap smear.
AB  - OBJECTIVE: To identify cytologic parameters on Pap smears of women with an
      atypical squamous cells of undetermined significance (ASCUS) diagnosis that could
      help cytologists to indicate whether a particular ASCUS case is most likely
      related to cervical intraepithelial neoplasia (CIN) grade 1 or 2/3. STUDY DESIGN:
      A total of 360 eligible women diagnosed with ASCUS and referred to the colposcopy
      clinic of Saint-Sacrement Hospital participated in the study. Eligible women were
      those aged 18-50 years, newly diagnosed with ASCUS, with no history of cervical
      biopsies or treatment, and not pregnant at the time of the visit. Colposcopically
      directed biopsies of lesions were obtained. All Pap smears were reviewed
      according to 36 different cytomorphologic criteria. The regression logistic model
      was used to estimate the odds ratios (ORs) for the associations between cytologic
      criteria observed in smears and the diagnosis of CIN made on biopsies. All
      cytologic criteria significantly (P < .05) associated with CIN were entered in
      the models, and a backward selection was done to determine independent cytologic
      predictors of CIN 1 and 2/3. RESULTS: Biopsies revealed that 22.2% of the study
      population had concurrent CIN. CIN I and 2/3 were identified in 61 (16.9%) and 19
      women (5.3%), respectively. Clear perinuclear spaces (OR = 2.5, P = .002) and
      moderate nuclear atypia (OR = 4.4, P = .02) were two cytologic criteria
      independently associated with CIN 1. Four independent predictors of CIN 2/3 were
      identified: the presence of clear perinuclear spaces (OR = 5.9, P = .004),
      hyperchromasia (OR = 3.9, P = .04), moderate anisokaryosis (OR = 13.1, P = .01
      and increased nuclear volume of metaplastic cells (OR = 5.1, P = .007).
      CONCLUSION: These observations may help cytologists to better categorize ASCUS
      lesions as intraepithelial ones and will also contribute to improving the
      Bethesda definition of ASCUS. Further studies are planned to validate these
      observations.

PMID- 10934952
TI  - Cytologic grading of invasive breast carcinoma. Correlation with
      clinicopathologic variables and predictive value of nodal metastasis.
AB  - OBJECTIVE: To estimate cytologic grade and correlate it with the other known
      prognostic factors, such as tumor differentiation, growth fraction, estrogen
      receptor status and nodal status. STUDY DESIGN: Fine needle aspirates from 104
      invasive ductal carcinomas were stained by the Papanicolaou method and examined
      for necrosis, cellular size, nuclear/cytoplasmic ratio, nuclear pleomorphism,
      nucleoli, chromatin granularity and density of chromatin. We established a
      semiquantitative scoring system based on the above features and correlated
      cytologic findings with clinicopathologic variables. RESULTS: Histologic grade
      correlated positively with cytologic grade and negatively with estrogen receptor
      positivity. Moreover, high cytologic grade was associated with nodal metastasis
      and proliferative index labeling by MIB-1. CONCLUSION: This study showed that our
      grading system for breast cancer on fine needle aspiration cytology is feasible
      on a routine diagnostic basis. Cytologic grading can provide more information
      than usual on tumor biologic behavior.

PMID- 10934953
TI  - Differentiating large cell lymphoma from indolent small B-cell lymphoma in fine
      needle aspirates using p53, PCNA and transformed lymphocyte count.
AB  - OBJECTIVE: To determine the usefulness of proliferating cell nuclear antigen
      (PCNA), p53 protein expression and transformed lymphocyte count (TLC) as
      adjunctive tests to differentiate indolent small B-cell lymphoma from large cell
      lymphoma in fine needle aspiration biopsies. STUDY DESIGN: Aspirates of
      lymphoproliferative disorders from April 1993 to January 1997 were reviewed. The
      percentage of TLCs was determined on the Papanicolaou smear. The percentage and
      intensity of p53 and PCNA immunocytochemical staining was evaluated on cell block
      sections. These results were compared and correlated with the final diagnoses
      based on available morphology, flow cytometry and clinical history. RESULTS:
      There were 40 cases of non-Hodgkin's lymphoma and 12 reactive lymph nodes.
      Adequate cell blocks were available on 16 large cell lymphomas, 7 grade 1-2
      follicular center cell lymphomas, 6 mucosal associated lymphoid tissue lymphomas,
      2 small lymphocytic lymphomas and 2 mantle cell lymphomas. Average TLC and p53
      nuclear staining was highest in large cell lymphomas (57% TLC and 24% p53),
      followed by grades 1 and 2 follicular lymphomas (14% TLC and 15% p53) and lowest
      in other indolent lymphomas (< 10% TLC and < 1% p53). Average PCNA staining was
      highest in large cell lymphomas (46%) and lowest in small lymphocytic lymphomas
      (7%); however, TLC was the best parameter for differentiating large cell lymphoma
      from indolent small B-cell lymphoma. CONCLUSION: TLC differentiated large cell
      lymphoma from indolent small B-cell lymphoma better than either p53 or PCNA alone
      or in combination. Significant overlap between categories limits usefulness of
      these immunocytochemical stains for differentiating these entities.

PMID- 10934954
TI  - Reproducibility in double scanning of cervical smears with the PAPNET system.
AB  - OBJECTIVE: To determine the reproducibility of the PAPNET scanning station
      (Neuromedical Systems, Inc., Suffern, New York, U.S.A.) in selecting cells from a
      cervical smear. STUDY DESIGN: We compared the images of 196 smears that were
      scanned on two occasions by the PAPNET scanning station on two monitors
      simultaneously and compared the cellular contents and technical records provided
      by the scanning station. The sample consisted of 62 positive smears (mild
      dysplasia and more) and 134 negative smears. RESULTS: Although differences were
      found in the technical information provided by the scanning station (kappa = .65,
      95% confidence interval [CI] = .51-0.79) and in the reported percentages of air
      bubbles (kappa = .60, 95% CI = .51-.68), the detection of abnormal cases was not
      affected. Furthermore, the agreement on microscopic review was excellent (kappa =
      .92, 95% CI = .88-.96). In nine cases that did not differ in tech code or
      percentage of air bubbles, however, differences were found in the cellular
      content of the tiles that would have led to different advice for additional
      microscopic review. This would have had important clinical consequences in two
      cases because a serious abnormality would have been missed. CONCLUSION: The
      consistency of the PAPNET scanning system is somewhat on the low side in
      providing technical information, although this did not affect the clinical
      outcome. In nine cases, for example, we found differences in the demonstration of
      cells in the tiles on the screen; two would have had clinical consequences. It is
      important to set goals for the performance of the machine and to incorporate them
      in the procedures to be used as standard practice. This is especially true when
      the scanning stations are going to be operated on site in the cytology
      laboratory.

PMID- 10934955
TI  - Glandular and squamous atypia and intraepithelial lesions in atrophic
      cervicovaginal smears. One institution's experience.
AB  - OBJECTIVE: To review the cytologic features and follow-up histologic findings in
      atrophic cervicovaginal smears with the diagnoses of glandular or squamous atypia
      or intraepithelial lesion. STUDY DESIGN: A total of 228 cases were included in
      the study. The selection criteria included: age > 48 years and a diagnosis of
      either atypical glandular cells (AGC) (51 cases), cellular changes suggestive of
      human papillomavirus (HPV) infection (S/O HPV, 97 cases), low grade squamous
      intraepithelial lesion (LSIL) (60 cases) or high grade squamous intraepithelial
      lesion (HSIL) (20 cases). Follow-up biopsy information was available for 103
      cases (45%). RESULTS: From the AGC group, 35 (69%) cases had tissue studies; 14
      (40%) cases showed glandular lesions; 5 (14%) showed squamous intraepithelial
      lesion (SIL) and atypical cells. Follow-up information was available for 32 (33%)
      cases classified as S/O HPV; significant lesions (glandular/squamous) were found
      in 11 (34%). In the LSIL category, 22 (37%) cases had follow-up; 16 (73%) showed
      SIL. In the HSIL category, 14 cases (70%) underwent biopsy, and all showed SIL
      (four LSIL and nine HSIL) or squamous cell carcinoma. CONCLUSION: Even though
      atrophy-related epithelial changes often pose diagnostic difficulties in the
      interpretation of postmenopausal smears, application of reproducible and
      established cytologic criteria in diagnosing SIL and/or glandular lesions can
      improve diagnostic accuracy and result in selection of patients for follow-up
      tissue studies.

PMID- 10934956
TI  - Screening parameters for ThinPrep and conventional gynecologic cytology via
      automated monitoring.
AB  - OBJECTIVE: To compare diagnostic discrepancies and screening parameters between
      conventional (CP) and ThinPrep (TP) (Cytyc Corporation, Boxborough,
      Massachusetts, U.S.A.) cervicovaginal samples using Pathfinder (Neopath, Redmond,
      Washington, U.S.A.). STUDY DESIGN: Pathfinder tracked average screening time,
      percent slide coverage and percent overlap of viewing fields for CP and TP. False
      negative rate (FNR) was determined by rescreening 10% of random and high-risk
      negative cases. CP and TP FNR with Pathfinder were compared to control groups
      without Pathfinder. RESULTS: A total of 46,393 Pathfinder cases were evaluated
      (43,354 CP, 3,039 TP) as compared to 62,981 without Pathfinder (60,307 CP, 2,674
      TP). FNR was calculated for 12,983 negatives. Using Pathfinder resulted in a
      significant reduction in FNR for CP atypical squamous cells of undetermined
      significance and atypical glandular cells of undetermined significance cases. No
      decrease in FNR was observed for CP squamous intraepithelial lesions or for TP
      cases. TP slides were screened 66 seconds faster on average than CP. With
      electronic feedback, mean percent slide coverage and percent overlap were similar
      between CP and TP cases. Without feedback, coverage dropped and overlap increased
      slightly for both CP and TP. Technologists screened faster with feedback, saving
      an average of 50 seconds on CP and 41 seconds on TP. CONCLUSION: Pathfinder
      significantly reduced FNR for CP but not TP. Technologists screened TP
      significantly faster than CP while maintaining similar coverage and overlap.
      Pathfinder feedback itself may decrease screening time.

PMID- 10934957
TI  - Cellularity of lobular carcinoma and its relationship to false negative fine
      needle aspiration results.
AB  - OBJECTIVE: To evaluate the cytocellularity and histocellularity of lobular
      carcinoma (LC) and the relationship to high false negative results of fine needle
      aspiration cytology (FNAC). STUDY DESIGN: In this retrospective study,
      cellularity was studied in 60 cases of classic LC, LC variants and lobular
      carcinoma in situ, comparing cytologic smears to their corresponding histologic
      sections. The cytologic smears were grouped into acellular, low, moderate and
      high categories, and the histologic sections were grouped into low, moderate and
      high categories. RESULTS: Malignancy or suspicion of malignancy was diagnosed in
      78% of cases. Overall cytocellularity showed acellularity or low cellularity in
      60% of cases, while overall histocellularity showed moderate or high cellularity
      in 95% of cases. When the cytocellularity was moderate or high, the corresponding
      histocellularity always showed moderate or high histocellularity. When the
      cytocellularity was low, the corresponding histology showed low histocellularity
      in 6.3% of cases. Thus, in acellular and low cellular aspirations, corresponding
      histocellularity may not be the contributing factor toward low cellular yield. In
      this study, 22% of cases were diagnosed as false negative, 40% were diagnosed as
      suspicious, and 38% were called positive. Only 17% of positive cases were
      diagnosed as LC. A large number of LC were misdiagnosed by FNAC as duct cell
      carcinoma, and most cases of low histocellularity were of the classic type.
      CONCLUSION: The results of this study suggest that in the majority of cases of
      LC, cellular yield of FNAC is disproportionately lower than expected when
      compared to the corresponding histocellularity. Awareness of modest cellularity
      and subtle cytologic features will aid in the correct preoperative diagnosis of
      LC, and false negative diagnoses can be minimized.

PMID- 10934958
TI  - Three-dimensional cytomorphology and its relationship with clinical stage in fine
      needle aspiration biopsy of papillary thyroid carcinoma.
AB  - OBJECTIVE: To elucidate three-dimensional (3-D) cytomorphology and its
      relationship with clinical stage in fine needle aspiration biopsy (FNAB) of
      papillary thyroid carcinoma (PTC). STUDY DESIGN: FNAB was performed in tumors
      from 34 patients with PTC. The aspirate was stained and observed under a light
      microscope (LM). The aspirate was also fixed, dehydrated, critical point dried,
      spattered with gold ions and observed with a scanning electron microscope (SEM).
      Findings under SEM were correlated with the presentation under LM and also with
      clinical stage. As a control, FNAB was also performed on a normal part of the
      thyroid in six patients. RESULTS: Under SEM, normal thyroid cells appeared as
      round, scattered cells or sheets with a uniform honeycomb cellular arrangement.
      In PTC, cell sheets with uniform nuclear morphology under LM usually showed a
      uniform cell arrangement and with distinct cell borders under SEM. Cell sheets
      with nuclear pleomorphism under LM usually showed a more-disorganized arrangement
      and with indistinct cell borders under SEM. PTC at advanced clinical stages
      usually presented with a disorganized cell arrangement, indistinct cell borders
      and loss of microvilli. CONCLUSION: 3-D cytomorphology in FNAB of PTC was related
      to clinical stage and might be a prognostic factor for PTC.

PMID- 10934959
TI  - Diffuse alveolar damage. Morphologic features in bronchoalveolar lavage fluid.
AB  - OBJECTIVE: To evaluate the overall cytologic characteristics of diffuse alveolar
      damage (DAD) in bronchoalveolar lavage (BAL) specimens in search of features that
      could be useful in cytologic diagnosis. STUDY DESIGN: We evaluated BAL samples
      from patients with DAD obtained simultaneously with transbronchial biopsies (n =
      8) or open lung biopsies (n = 2) or within 24 hours of autopsy (n = 2). The
      material was processed routinely for cytologic and histologic evaluation.
      RESULTS: The smears were moderately to highly cellular. All cases had large
      numbers of alveolar macrophages and/or desquamated alveolar cells. The epithelial
      component displayed various degrees of nuclear atypia. Some epithelial clusters
      were three-dimensional, with peripheral cells showing clear cytoplasm, protruding
      outwards and resembling hobnails. Other aggregates appeared two-dimensional, as
      sheets of cells with flattened and dense cytoplasm (squamotized). Both types of
      cell clusters were often associated with dense, basophilic or amphophilic,
      amorphous extracellular material. Counterparts of all the cytologic features were
      observed in the histologic material, including atypia of the alveolar lining with
      hobnailing, squamotization, amorphous extracellular material and hyaline
      membranes. CONCLUSION: The cytologic features of BAL represent a constellation of
      alveolar cell injury. Based on these features, DAD can be correctly diagnosed or
      suggested in BAL samples in the appropriate clinical setting.

PMID- 10934960
TI  - Plasmacytoid myoepithelioma of the soft palate. Report of a case with cytologic,
      immunohistochemical and electron microscopic studies.
AB  - BACKGROUND: The plasmacytoid variant is a rare and controversial subtype of
      myoepithelioma that lacks myogenic differentation and the cytologic findings of
      which have not been reported previously. CASE: A 46-year-old man presented with a
      painless tumor located in the soft palate. Fine needle aspiration cytology (FNAC)
      showed odd-shaped cellular aggregates and single cells with round nuclei and
      finely granular cytoplasm resembling plasma cells together with strands of
      metachromatic stroma. The light, immunohistochemical and ultrastructural studies
      performed on the surgical specimen confirmed the initial cytologic diagnosis.
      CONCLUSION: Recognition of the cytologic findings of plasmacytoid myoepithelioma
      on needle aspirates allows a reliable and quick diagnosis that prompts correct
      management.

PMID- 10934961
TI  - Diagnostic pitfalls in fine needle aspiration cytology of pleomorphic lipoma. A
      case report.
AB  - BACKGROUND: Pleomorphic lipoma is an unusual pseudosarcomatous condition with
      characteristic morphology. Despite its pleomorphic appearance, it follows a
      benign course and does not recur or metastasize if completely excised. CASE: A 66
      year-old man presented with swelling in the back of the neck of approximately six
      months' duration. The focally cellular aspirate revealed round to oval,
      hyperchromatic cells, rare multinucleated cells and fragments of mature adipose
      tissue. On initial evaluation, the smear pattern suggested a malignant neoplasm.
      However, upon review of the cytologic material along with histology, the
      characteristic pattern, including floret cells, was recognized. CONCLUSION: The
      rarity of pleomorphic lipoma and the atypical cellular features of the aspirate
      can cause difficulty in diagnosing this entity. Awareness of this rare but not
      uncommon entity, along with clinical correlation, is crucial in arriving at the
      correct diagnosis.

PMID- 10934962
TI  - Subcutaneous metastasis from transitional cell carcinoma of the bladder diagnosed
      by fine needle aspiration biopsy. A case report.
AB  - BACKGROUND: Metastasis of transitional cell carcinoma (TCC) of the bladder to the
      skin and subcutaneous tissue is an uncommon finding. CASE: A 58-year-old man with
      a known case of high grade TCC of the bladder, presented with a right paraspinal
      mass. Clinically an abscess was suspected. Fine needle aspiration (FNA) showed
      many clusters and isolated malignant cells in an inflammatory background. The
      smears were diagnosed as positive for malignancy. CONCLUSION: It is essential to
      differentiate tumors metastatic to the skin and subcutaneous tissue from
      inflammatory lesions. FNA helped with the diagnosis in this case and prevented
      unnecessary biopsy.

PMID- 10934963
TI  - Cervical cytology and immunohistochemical features in endometrial adenocarcinoma
      simulating microglandular hyperplasia. A case report.
AB  - BACKGROUND: The histology of a few cases of adenocarcinoma simulating cervical
      microglandular hyperplasia (MGH-AdCa) has been reported. However, the cytologic
      features of MGH-AdCa in cervical smears and the immunohistochemical profile have
      not been described. CASE: A 73-year-old female presented with vaginal bleeding.
      The cervical Pap smear was initially interpreted by the cytotechnologist as
      "reactive endocervical cells" and was referred for cytopathologist review. The
      final interpretation was atypical glandular cells of undetermined significance
      (AGUS), probably neoplastic. Endometrial biopsy and total abdominal hysterectomy
      with bilateral salpingo-oophorectomy showed International Federation of
      Gynecologists and Obstetricians grade 1 endometrial carcinoma. The superficial
      component of the tumor resembled cervical microglandular hyperplasia (MGH); the
      deeper component had an endometrioid pattern. The Pap smear predominantly showed
      a glandular component with features of MGH. However, the presence of scattered
      single cells with hyperchromatic nuclei, one to three nucleoli, easily detectable
      mitotic figures, randomly scattered apoptotic bodies and focal, watery diathesis
      suggested a neoplastic process. Immunohistochemistry was studied on paraffin
      sections. In addition to other markers, the tumor cells were immunoreactive for
      carcinoembryonic antigen (CEA). CONCLUSION: Although the cervical Pap smear in
      this case had an MGH-like pattern, some features were atypical enough to suggest
      a diagnosis of AGUS, probably neoplastic. CEA immunoreactivity of MGH-AdCa could
      also help to differentiate it from MGH.

PMID- 10934964
TI  - Primitive neuroectodermal tumor of the uterus. A case report.
AB  - BACKGROUND: Primitive neuroectodermal tumor (PNET) is a rare tumor derived from
      fetal neuroectodermal cells. These tumors occur in the central nervous system and
      in peripheral locations. Histologic diagnosis is the standard since most of these
      tumors are detected at an advanced stage. CASE: A 17-year-old female presented
      with persistent vaginal bleeding. Physical examination revealed a 4-cm, hard,
      barrel-shaped cervix. A cervicovaginal smear was obtained. The specimen was
      hypercellular, with small to medium-sized, round, malignant cells. A diagnosis of
      PNET was made from the histologic sections of the surgical specimen. CONCLUSION:
      When numerous small round cells in a diffuse pattern are seen on a Pap smear, the
      differential diagnosis is long and difficult. However, with careful evaluation of
      the cytologic features, a few reasonable differential diagnoses can be reached.
      Furthermore, with liquid-based Pap smears, material is available for
      immunohistochemical staining to narrow the range even more. Using all resources,
      including a good clinical history, a cytopathologist can give the clinician an
      early diagnosis for intervention and treatment.

PMID- 10934965
TI  - Localized amyloidosis in nasopharyngeal carcinoma diagnosed by fine needle
      aspiration and electron microscopy. A case report.
AB  - BACKGROUND: The association of amyloidosis and tumors is well known, but only
      rarely has it been found in the nasopharynx. Moreover, only a single case of
      tumor-associated amyloidosis in the nasopharynx has been diagnosed by exfoliative
      cytology and reported in the English-language literature. We describe a case of
      localized amyloidosis in metastatic nasopharyngeal carcinoma diagnosed by fine
      needle aspiration and confirmed by histology and electron microscopy. CASE:
      Bilateral neck enlargement appeared six months before consultation in a 57-year
      old man. Both masses were resected, and during exploration of the nasopharynx,
      several blind biopsies were taken. Smears from the fine needle aspirate showed
      malignant epithelial cells, consistent with metastatic carcinoma, and Congo red
      stain showed the presence of amyloid. Histologic examination of the resected
      cervical masses and nasopharyngeal biopsies confirmed the diagnosis of
      nasopharyngeal carcinoma, nonkeratinizing variant with amyloid, and metastases in
      two lymph nodes. Electron microscopic examination of a lymph node showed
      extracellular, ribbon-like amyloid deposits as well as masses of amorphous
      amyloid, apparently intracellular. CONCLUSION: The origin of this form of
      amyloidosis is unclear in this patient since he had no other known etiologic
      factors for the condition. Increased awareness of the potential association of
      these two conditions and the use of fine needle aspiration may reveal a higher
      frequency than hitherto reported.

PMID- 10934966
TI  - c-kit immunocytochemical staining in the cytologic diagnosis of metastatic
      gastrointestinal stromal tumor. A report of two cases.
AB  - BACKGROUND: Gastrointestinal stromal tumor (GIST) is a distinct group of
      mesenchymal neoplasms recently shown to exhibit differentiation toward
      interstitial cells of Cajal (ICC). C-kit (CD117), an immunocytochemical marker
      consistently expressed in normal ICC, is demonstrable in 81-100% of GISTs. We
      report two cases wherein immunocytochemical staining for c-kit aided in the
      diagnosis of metastatic GIST in the liver. CASES: Two patients, a 37-year-old
      female (case 1) and a 76-year-old male (case 2), presented with multiple nodules
      in the liver. They had a history of small bowel GIST resected 11 and 1 year
      earlier, respectively. Fine needle aspiration of the liver nodules showed loose
      aggregates or fascicles of spindle cells with elongated to oval nuclei, rare
      paranuclear vacuoles and eosinophilic cytoplasm. The spindle cells showed minimal
      (case 1) to moderate nuclear pleomorphism (case 2), with occasional mitotic
      figures seen in case 2. Immunocytochemical staining revealed strong and diffuse
      staining for c-kit; it was negative for actin, desmin, CD34 and S-100 protein.
      Thus, a diagnosis of metastatic GIST was rendered. Histologic review of the
      primary small bowel GISTs of both cases and the subsequently resected liver
      nodules in case 1 confirmed the diagnosis. CONCLUSION: Metastatic GIST may pose
      diagnostic problems due to its broad morphologic spectrum and variable cytologic
      atypia; in particular, distinction from leiomyosarcoma and other mesenchymal
      tumors is difficult. The diagnostic difficulty is compounded when the prior
      history of gastrointestinal tumor is not available or forgotten and when GIST is
      the initial presentation of the tumor. C-kit is a highly sensitive and reliable
      immunocytochemical marker that can aid in the diagnosis.

PMID- 10934967
TI  - Lymphoepitheliomalike carcinoma of the uterine cervix in cervicovaginal smears.

PMID- 10934968
TI  - Establishing a worldwide volunteer cervical cytology program.

PMID- 10934969
TI  - Fine needle aspiration findings in granular cell myoblastoma of the tongue.

PMID- 10934970
TI  - Fine needle aspiration diagnosis of extramedullary hematopoiesis presenting as a
      right lung mass.

PMID- 10934971
TI  - Fine needle aspiration biopsy for the diagnosis of secondary amyloidosis.

PMID- 10934972
TI  - Pesticides, policies and parents.

PMID- 10934973
TI  - How long are TB patients infectious?

PMID- 10934974
TI  - The shoulder bone's connected to the...

PMID- 10934975
TI  - Renal transplantation in Saskatchewan.

PMID- 10934976
TI  - Vigilance is needed.

PMID- 10934977
TI  - Barriers to appropriate diabetes management among homeless people in Toronto.
AB  - BACKGROUND: Homeless people are more likely to have chronic medical conditions
      and to encounter barriers to health care than the general population. In this
      study we identify barriers to appropriate disease management among homeless
      adults with diabetes mellitus in Toronto. METHODS: People with diabetes were
      surveyed at homeless shelters in Toronto. Information was obtained on demographic
      characteristics, diabetes history, access to health care, substance abuse and
      mental illness. Participants' descriptions of the difficulties they experienced
      in managing their diabetes were analysed qualitatively. Hemoglobin A1c levels
      were used to assess adequacy of glycemic control. RESULTS: Fifty people completed
      the survey (response rate 83%). Of the respondents 82% were male and 64% were
      white. Type 2 diabetes had been diagnosed in 86%, with 62% of all participants
      taking oral agents alone and 28% taking insulin alone. Overall, 72% of the
      participants reported experiencing difficulties managing their diabetes: the most
      common were related to diet (type of food at shelters and inability to make
      dietary choices, reported by 64%) and scheduling and logistics (inability to get
      insulin and diabetic supplies when needed and inability to coordinate medications
      with meals, reported by 18%). Although alcohol use, cocaine use and mental health
      problems were common, few respondents cited these issues as barriers to diabetes
      management. According to Canadian Diabetes Association guidelines, glycemic
      control was inadequate in 44% of the people tested. INTERPRETATION: In Toronto,
      most homeless adults with diabetes report difficulties managing their disease,
      and poor glycemic control is common.

PMID- 10934979
TI  - Physician payment for the care of homeless people.

PMID- 10934978
TI  - Cancer care workers in Ontario: prevalence of burnout, job stress and job
      satisfaction.
AB  - BACKGROUND: Cancer Care Ontario's Systemic Therapy Task Force recently reviewed
      the medical oncology system in the province. There has been growing concern about
      anecdotal reports of burnout, high levels of stress and staff leaving or
      decreasing their work hours. However, no research has systematically determined
      whether there is evidence to support or refute these reports. To this end, a
      confidential survey was undertaken. METHODS: A questionnaire was mailed to all
      1016 personnel of the major providers of medical oncology services in Ontario.
      The questionnaire consisted of the Maslach Burnout Inventory, the 12-item General
      Health Questionnaire, a questionnaire to determine job satisfaction and stress,
      and questions to obtain demographic characteristics and to measure the staff's
      consideration of alternative work situations. RESULTS: The overall response rate
      was 70.9% (681 of 961 eligible subjects): by group it was 63.3% (131/207) for
      physicians, 80.9% (314/388) for allied health professionals and 64.5% (236/366)
      for support staff. The prevalence of emotional exhaustion were significantly
      higher among the physicians (53.3%) than among the allied health professionals
      (37.1%) and the support staff (30.5%) (p < or = 0.003); the same was true for
      feelings of depersonalization (22.1% v. 4.3% and 5.5% respectively) (p < or =
      0.003). Feelings of low personal accomplishment were significantly higher among
      physicians (48.4%) and allied health professionals (54.0%) than among support
      staff (31.4%) (p < or = 0.002). About one-third of the respondents in each group
      reported that they have considered leaving for a job outside the cancer care
      system. Significantly more physicians (42.6%) than allied health professionals
      (7.6%) or support staff (4.5%) stated that they have considered leaving for a job
      outside the province. INTERPRETATION: The findings support the concern that
      medical oncology personnel are experiencing burnout and high levels of stress and
      that large numbers are considering leaving or decreasing their work hours. This
      is an important finding for the cancer care system, where highly trained and
      experienced health care workers are already in short supply.

PMID- 10934980
TI  - Homelessness: reducing health disparities.

PMID- 10934981
TI  - Asymptomatic hyperparathyroidism: is the pendulum swinging back?

PMID- 10934982
TI  - Rheumatology: 6. Localized rheumatism.

PMID- 10934985
TI  - American MDs reject moratorium on capital punishment.

PMID- 10934984
TI  - Choosing a first-line drug in the management of elevated blood pressure: what is
      the evidence? 2: Beta-blockers.
AB  - Elevated blood pressure is associated with an increased risk of cardiovascular
      illness and death. Efforts to reduce that risk have led to recommendations for a
      wide array of nondrug and drug therapies. Choosing the optimal first-line drug
      for hypertensive patients should address a hierarchy of treatment goals: decrease
      in morbidity and mortality associated with hypertension, decrease in blood
      pressure, good tolerance, dosing convenience and low cost. This article examines
      the evidence for beta-blockers as a class of first-line antihypertensive drugs in
      light of these treatment goals. The evidence indicates that beta-blockers are
      probably not as effective in reducing morbidity and mortality as low-dose
      thiazide diuretics and that there may be significant differences in effectiveness
      among various beta-blockers.

PMID- 10934983
TI  - Primary hyperparathyroidism: pathophysiology and impact on bone.
AB  - Primary hyperparathyroidism has been associated with bone loss, especially at
      cortical skeletal sites. Results from studies evaluating the mineral density of
      cancellous bone have been more difficult to interpret. Most densitometry studies
      support the concept that the parathyroid hormone appears to be catabolic at
      cortical sites and may have anabolic effects at cancellous bone sites. Studies
      completed to date, however, have been limited by design, definitions of fracture
      and inadequate control groups. Primary hyperparathyroidism is now increasingly
      being detected during the asymptomatic phase. The need for parathyroidectomy has
      been questioned in such patients because there may be no disease progression in
      the absence of surgery. Medical management of primary hyperparathyroidism has to
      date been limited to estrogen replacement therapy in postmenopausal women.
      Identification of the calcium receptor has improved our understanding of calcium
      homeostasis, and significant reductions in calcium receptor levels have been
      detected in parathyroid adenomas. Thus, a new class of therapeutics may include
      the calcimimetic agents. Bisphosphonates are also currently being evaluated with
      regard to their impact on fracture prevention and their beneficial effects on
      bone mineral density.

PMID- 10934986
TI  - Most Canadians welcome genetic testing.

PMID- 10934987
TI  - CMPA, OMA try to heal rift over regional rating.

PMID- 10934988
TI  - Health workers take to streets to reduce impact of homelessness.

PMID- 10934989
TI  - Escherichia coli O157:H7.

PMID- 10934990
TI  - Organ and tissue donation and transplantation (update 2000). Canadian Medical
      Association.

PMID- 10934991
TI  - Community accountability among hospitals affiliated with health care systems.
AB  - The shift from local, community-based hospitals to more complex, multilevel
      delivery systems raises questions about the community accountability exercised by
      hospitals. A national sample of community hospitals is the basis of this study,
      which examines the ways that community accountability is exercised by the
      governing boards of hospitals affiliated with health care systems and how such
      institutions compare with hospitals not affiliated with a health care system.
      Results indicate that hospitals display community accountability in a variety of
      ways. Boards of system-affiliated hospitals exercise community accountability
      most strongly in their information monitoring and reporting activities, whereas
      free-standing hospitals exercise community accountability through the structural
      and compositional attributes of their boards. Further, hospitals affiliated with
      different types of systems vary in the style and degree of accountability they
      demonstrate.

PMID- 10934992
TI  - Alternative funding policies for the uninsured: exploring the value of hospital
      tax exemption.
AB  - The tax exemption accorded private, nonprofit hospitals is being subjected to
      more scrutiny as the numbers of uninsured grow; meanwhile, charity care competes
      with market-driven priorities. Current public policies tie hospital tax exemption
      to the provision of charity care, but there is a gap in the size and distribution
      of values between tax exemption and the charity care that is provided. Most
      hospitals, in a study reported here, provided free care at a level below the
      value of their tax exemption, even when 50 percent of bad debt was included in
      the care value. However, hospitals in the poorest communities offered
      considerably more care than the value of their tax exemption, whereas those in
      wealthier communities offered considerably less. Policies at local, state, and
      federal levels should be designed to exert leverage on hospitals to provide free
      care at a level commensurate with the value of their tax exemptions.

PMID- 10934993
TI  - Hospitals sponsored by the Roman Catholic Church: separate, equal, and distinct?
AB  - For centuries, the Catholic Church has been a major social actor in the provision
      of health services, particularly health care delivered in hospitals. Through a
      confluence of powerful environmental forces at the beginning of the twenty-first
      century, the future of Catholic health care is threatened. Although Catholic
      hospitals are a separate case of private, nonprofit hospitals, they have
      experienced environmental pressures to become isomorphic with other hospital
      ownership types and, on some dimensions, they are equal. To keep pace with the
      changing demands of religion and the social role of the hospital, Catholic
      hospitals continue to redefine themselves. To justify a distinct and legitimate
      social role, more research should be conducted to develop and measure indicators
      of Catholic identity.

PMID- 10934994
TI  - The governance and management of effective community health partnerships: a
      typology for research, policy, and practice.
AB  - Community health partnerships (CHPs) are voluntary collaborations of diverse
      community organizations that have joined forces in order to pursue a shared
      interest in improving community health. Although these cross-sectoral
      collaborations represent a way to address social determinants of health and
      disease in society, they suffer from governance and management problems
      associated with interorganizational relationships in general and health care
      challenges specifically. A typology of effective governance and management
      characteristics provides a systematic, theoretically based way of addressing
      dimensions of governance and management and serves as a guide in constructing,
      maintaining, and measuring successful partnerships. It offers a multidisciplinary
      perspective for classifying important organizational issues, identifying barriers
      to successful development and sustainability, and facilitating the attainment of
      goals.

PMID- 10934995
TI  - Does medical insurance contribute to socioeconomic differentials in health?
AB  - Both access to insurance and health itself vary widely by socioeconomic status
      (SES). Are socioeconomic variations in health linked to insurance coverage or to
      factors that lie outside the medical care arena? Data from the Aging, Status, and
      the Sense of Control Survey were the basis of a representative U.S. national
      telephone survey conducted in 1995, and again in 1998. The results showed that
      persons with private insurance do not differ significantly from the uninsured in
      their self-reported health, physical functioning, or number of chronic
      conditions, whereas persons with public insurance report significantly worse
      health and more chronic conditions than the uninsured. These longitudinal results
      hold with adjustment for baseline health, SES, change in social status, and the
      hazard of attrition. Medical insurance does not mediate any associations between
      SES and health. Medical insurance of all kinds, however, does reduce difficulties
      in paying medical bills, and Medicaid is associated with more doctor visits and
      prescription drugs.

PMID- 10934996
TI  - Patients, families, and organ donation: who should decide?
AB  - Although 69 to 75 percent of U.S. adults say they would be willing to become
      organ donors, half of the families that are asked to consider donating the organs
      of a deceased family member refuse to consent. This discrepancy is most
      noticeable when the refusal of a family conflicts with the known wishes of a
      patient. It is the practice of nearly all organ procurement organizations in the
      United States not to procure organs or tissue when families refuse, even if the
      patient's wishes have been documented. Recently, the Center for Organ Recovery
      and Education (CORE) adopted a controversial policy of acting on the documented
      wishes of individuals to donate, independent of family consent. An examination of
      the moral and political issues raised by this policy lead to the conclusion that
      the CORE policy is not only justified, but morally required.

PMID- 10934997
TI  - The pharmacology of anesthetic drugs in elderly patients.
AB  - Elderly patients are more sensitive to anesthetic drugs than younger patients.
      This increased sensitivity has a pharmacokinetic basis if the dose produces a
      higher drug concentration in an elderly patient than in a younger patient. The
      increased sensitivity has a pharmacodynamic basis if the same concentration
      produces a more profound drug effect in elderly patients. This article reviews
      the mechanisms of increased sensitivity of elderly patients to opioids,
      hypnotics, amnestica, and muscle relaxants.

PMID- 10934998
TI  - Autonomic and cardiovascular function in the geriatric patient.
AB  - The elderly patient is at an increased risk for hemodynamic instability during
      anesthesia. The underlying mechanisms are primarily a decrease in the beta
      receptor response to stimulation, stiffening of the connective tissue throughout
      the cardiovascular system, and increased vascular resistance during surgical
      stress and an increased dependency on cardiac filling. Unfortunately, the ability
      to maintain a steady preload diminishes with age and in general, changes in blood
      volume are buffered less effectively. Anesthetic management requires closer
      monitoring of blood pressure and a greater emphasis on vasomotor tone than on
      fluid administration when treating hypotension.

PMID- 10934999
TI  - Respiratory function in the elderly.
AB  - Aging reduces the reserve capacity of virtually all pulmonary functions. Age
      related alterations in the respiratory system are based on structural changes
      that lead to functional impairment of gas exchange. Pulmonary complications
      during anesthesia and the postoperative period are significantly increased in
      elderly patients with pre-existing diseases. The physiologic changes in the aged
      respiratory system and their anesthetic implications are reviewed in this
      article.

PMID- 10935000
TI  - Central nervous system dysfunction after anesthesia in the geriatric patient.
AB  - Cerebral infarction, bleeding, long-lasting hypofusion, and profound hypoxia are
      well-known factors behind central nervous system dysfunction after anesthesia.
      Other explanations may be the metabolic-endocrine stress response and psychologic
      factors related to changes in the environment. The clinical presentations can be
      obvious as in cerebral death or stroke but delirium also may be readily
      recognized. A more subtle and long-lasting deterioration in cognitive function is
      called postoperative cognitive dysfunction. This condition can only be detected
      with the use of neuropsychologic testing and recently, postoperative cognitive
      dysfunction has been detected as the most common cerebral complication after
      noncardiac surgery in elderly patients.

PMID- 10935001
TI  - Preoperative assessment of the elderly patient.
AB  - Organ system functional reserve variability increases progressively with age. In
      elderly patients, cardiopulmonary, central nervous system, and metabolic
      functional reserve seem to be the most important predictors of the ability to
      undergo surgery. Directed testing for the assessment of organ system functional
      reserve and identification of organs at risk, rather than the diagnosis of
      disease itself, is the primary goal of preoperative evaluation prior to surgery
      and is essential to the formulation of an effective anesthetic plan. The risks of
      adverse drug interaction, already high in the elderly, make a thorough review of
      the indications and dosage of perioperative medication an important part of the
      preoperative assessment process.

PMID- 10935002
TI  - Choosing general versus regional anesthesia for the elderly.
AB  - Although clinical perceptions and theoretic considerations suggest regional
      anesthesia should be safer than general anesthesia in elderly patients, current
      studies indicate no difference in outcomes. Regional anesthesia may still prove
      superior to general anesthesia if the right patient population or right endpoints
      are identified for comparison. A study of consequence of outcome, comparing the
      two approaches has created an expansion of the definition of anesthesia-related
      complications.

PMID- 10935003
TI  - Positioning aged patients.
AB  - While geriatric patients do not present problems of positioning that are found
      only in their age group, their acquired infirmities may intensify the likelihood
      and severity of complications common to younger peers. Careful preoperative
      evaluation of potential positioning problems is needed, as is explicit recording
      of positioning recommendations in a manner easily encountered by appropriate
      members of the care team. The physiologic impact of those infirmities that are
      present upon the ability of the patient to recover from the surgical and
      anesthetic experience should be kept clearly in mind throughout the procedure,
      and techniques involved should be modified accordingly. A postoperative survey of
      potential complications of positioning should be made expeditiously to permit
      indicated treatment to be applied rapidly to an elderly patient.

PMID- 10935004
TI  - Geriatric pain management. The anesthesiologist's perspective.
AB  - Geriatric patients have a unique physiology that makes their pain management
      problematic. This article reviews the issue of geriatric pain management from the
      perspective of the anesthesiologist. It looks at the main causes of geriatric
      chronic pain and emphasizes the different analgesic modalities available that can
      provide maximum relief and minimal potential side effects.

PMID- 10935005
TI  - Management of cardiopulmonary resuscitation.
AB  - Since cardiopulmonary resuscitation was first described in 1960, it has become a
      standardized medical intervention. Separate guidelines have been developed for
      the neonatal and pediatric population, but none exist for the elderly population.
      This review will discuss recent available outcome data on resuscitation of the
      elderly and the known physiologic changes with aging that may affect decisions
      made during resuscitation.

PMID- 10935006
TI  - Ethical decisions in perioperative elder care.
AB  - Settings involving the extremes of age and illness are the most complex in
      ethical deliberation and require sound principles that can be clearly applied to
      individual situations. This article discusses how one's view of the aging process
      effects clinical decision making. The basic principles of medical ethics
      (autonomy, beneficence, nonmaleficence, and justice) are discussed along with
      alternative ethical paradigms that may be more appropriate to the elderly
      population. Issues such as informed consent, do not resuscitate orders in the
      operating room, and controversies in end-of-life palliative care specifically
      impact the role of the anesthesiologist. Anesthesiologists, as medical
      professionals in a health care team, have a great stake in ethical decision
      making and the ethics of health care policy.

PMID- 10935007
TI  - Palliative care and end-of-life issues.
AB  - As stated, the goal of palliative care is the achievement of the best quality of
      life for patients and their families. It incorporates many aspects of care:
      providing physical comfort, psychosocial and spiritual support, and providing
      various services in order to achieve this goal. The skills described should be a
      priority in the practice of all types of medicine because the goal of palliative
      care is among the central tenets of the medical profession.

PMID- 10935008
TI  - The pharmacology of local anesthetics.
AB  - The pharmacology of local anesthetics is an integration of the basic physiology
      of excitable cells and the mechanism by which local anesthetics are capable of
      interrupting conduction of neural messages. The common characteristics of the
      molecules with local anesthetic action have been identified and can explain the
      properties of the agents. These same chemical characteristics also explain
      toxicity of these agents and differences that exist between local anesthetics
      with similar structure.

PMID- 10935009
TI  - New developments in spinal anesthesia.
AB  - Spinal anesthesia can be used effectively and efficiently for a variety of cases
      in both the inpatient and the ambulatory surgery setting. Choice of agent, dose,
      distribution, use of adjuncts, and occasionally the use of continuous spinal
      anesthesia can tailor the spinal anesthetic to a specific type and duration of
      surgery. Although spinal anesthesia is extremely safe, adherence of new
      guidelines for patients receiving anticoagulant drugs, LMWH in particular, may
      minimize the risk of neurologic injury from spinal bleeding. At present,
      intrathecal adjuncts, such as neostigmine and clonidine used with local
      anesthetics, have shown limited usefulness, whereas lipophilic opioids, such as
      fentanyl, appear to increase duration and quality of spinal block without
      increasing the time to recovery. In the future, shorter-acting local anesthetics,
      possibly in conjunction with continuous catheter technologies, may reduce
      recovery times after spinal anesthesia without increasing risk. Spinal agents
      with long-acting analgesic properties that do not produce sensorimotor deficits
      may go beyond the immediate perioperative period and relieve postoperative pain.
      Currently there is controversy surrounding the use of spinal lidocaine and the
      occurrence of TNS, especially in the outpatient setting. The prudent use of small
      dose bupivacaine and possibly procaine may reduce this risk, further supporting
      the use of spinal anesthesia for ambulatory as well as inpatient surgical
      procedures.

PMID- 10935010
TI  - New developments in epidural anesthesia and analgesia.
AB  - Several recent advances in epidural anesthesia and analgesia have been reviewed.
      Perhaps the most exciting area of anticipated future developments relates to the
      continued development of novel analgesic agents and new epidural delivery
      systems. There appears to be some movement toward an increased use of intrathecal
      or peripheral neural blockade techniques for some clinical situations where
      epidural anesthesia and analgesia have been previously used; however, the ability
      to provide anesthesia and analgesia to relatively large areas of the body with a
      single injection or continuous catheter technique without the associated risks of
      dural puncture and intrathecal catheter placement will continue to assure
      epidural anesthesia and analgesia techniques a prominent role in anesthesia and
      pain management.

PMID- 10935011
TI  - The combined spinal-epidural technique.
AB  - Epidural and spinal blocks are well-accepted regional techniques, but they have
      several disadvantages. The CSE technique can reduce or eliminate the risks of
      these disadvantages. CSE block combines the rapidity, density, and reliability of
      the subarachnoid block with the flexibility of continuous epidural block to
      extend duration of analgesia. The CSE technique is used routinely at many
      institutions, particularly for major orthopedic surgery and in obstetrics. It has
      been used in tens of thousands of patients without any reports of major problems.
      Although at first sight the CSE technique appears to be more complicated than
      epidural or spinal block alone, intrathecal drug administration and siting of the
      epidural catheter are both enhanced by the combined, single-space, needle-through
      needle method. Concerns about the epidural catheter entering the theca via the
      small puncture hole are now considered to be unfounded, but as with all epidural
      catheter techniques, vigilant monitoring of the patient during and after any
      injection is paramount. CSE is an effective way to reduce the total drug dosage
      required for anesthesia or analgesia. The intrathecal injection achieves rapid
      onset with minimal doses of local anesthetics and opioids, and the block can be
      prolonged with low-dose epidural maintenance administration. In addition, the
      sequential CSE method can be used to extend the dermatomal block with minimal
      additional drugs or even saline. Reduction in total drug dosage has made truly
      selective blockade possible. Many studies have confirmed that low-dose CSE with
      local anesthetic and opioid, or low-dose epidural block alone, will provide
      effective analgesia with minimal motor and proprioceptive block. Such neurologic
      selective blockade has made it possible for most patients to walk and bear down
      normally in labor or postoperatively. There remains concern about the risk of
      infection being increased when the CSE technique is used in place of epidural
      block alone. Despite a recent flurry of reports of meningitis with CSE
      procedures, there is no evidence the CSE block is more hazardous than epidural or
      subarachnoid block alone. Arguably, the single-space, needle-through-needle CSE
      technique will continue to improve with new needle designs and other advances to
      improve further the success rate and reduce complications, such as neurotrauma,
      PDPH, and infection. Over the past decade it has become clear that the CSE
      technique is a significant advance in regional blockade.

PMID- 10935012
TI  - Upper extremity nerve blocks.
AB  - Anatomy favorable to the application of regional blockade, the capacity to
      decrease latency and prolong blockade, and the opportunity to facilitate recovery
      and decrease costs create a constellation of factors that have the potential to
      make upper extremity blockade a tremendously rewarding application of modern
      regional anesthetic technique. These rewards can be realized by the motivated
      anesthesiologist and shared with patients, surgical colleagues, and hospital
      administrators.

PMID- 10935013
TI  - Lower extremity nerve blocks.
AB  - Lower extremity nerve blocks have not become as popular as upper extremity blocks
      for anesthesia; however, the use of lower extremity nerve blocks will become more
      widespread, as teaching programs are now providing more regional anesthesia
      experiences for their trainees so that the anesthesia provider will have the
      familiarity to use these blocks. To increase the enthusiasm among our surgical
      colleagues, we must begin to use these blocks for surgery, and if the block must
      be supplemented with local anesthetic or a light general anesthetic, we must
      educate them that the block is not a failure but a success, as it will provide
      analgesia after surgery in a method of multimodal pain control. Lower extremity
      nerve blocks will become more popular when it is realized that they are an
      effective way of increasing operating room efficiency. Because the block may be
      placed in an induction room, there is no induction or emergence in the operating
      room. Patients may be discharged without the need for pain medications, thus
      lowering the incidence of nausea postoperatively and decreasing PACU and
      discharge times.

PMID- 10935014
TI  - Regional anesthesia for ambulatory surgery.
AB  - Ambulatory surgery is increasing at unprecedented rates with more complex
      procedures being performed. This article reviews the benefits of the use of
      regional anesthesia during ambulatory surgeries. Regional anesthesia, by putting
      the anesthetic at the surgical site, provides ideal conditions for ambulatory
      surgery and provides a smooth, predictable post-operative course.

PMID- 10935015
TI  - Regional anesthesia in pediatrics.
AB  - The use of regional anesthetic techniques in infants and children has become
      increasingly accepted as standard care. The most commonly performed regional
      anesthetic techniques used in pediatric patients are the caudal and lumbar
      approaches to the epidural space, ilioinguinal/iliohypogastric, and penile nerve
      blockade. These and other techniques are reviewed, along with specific issues
      such as risks, benefits, drug dosage, and local anesthetic toxicity. The safety
      of regional anesthetic techniques in pediatric patients is addressed, with
      recommendations for prevention and treatment of complications.

PMID- 10935016
TI  - Regional anesthesia for obstetrics.
AB  - The practice of administration of labor analgesia has undergone dramatic changes
      this decade. This is largely attributable to unparalleled interest in the field
      by many dedicated and capable investigators around the world. Through their
      efforts, this decade has witnessed the introduction of new techniques (pencil
      point needles, CSE, PCEA, ultradilute epidural regimens) that have permitted us
      to come closer than ever to realizing the goal of complete relief from the pain
      and suffering of labor while safeguarding the well-being of mother and child and
      minimizing effects on the labor process. Neuraxial anesthetic techniques and
      modern multimodal analgesic approaches to postoperative pain relief now minimize
      the effects of cesarean delivery on maternal satisfaction and participation in
      the birth process.

PMID- 10935017
TI  - The role of epidural anesthesia and analgesia in postoperative outcome.
AB  - There is increasing evidence to support the hypothesis that epidural anesthesia
      and analgesia (EAA) can improve surgical outcome by reducing postoperative
      morbidity and hastening recovery. Likely benefits include decreased incidence of
      cardiac complications in high-risk patients; lower incidence of pulmonary
      complications, specifically pneumonia, atelectasis, and hypoxemia in patients at
      risk for pulmonary complications; lower incidence of vascular graft occlusion
      after lower extremity revascularization; lower incidence of DVT and pulmonary
      embolus; suppression of the neuroendocrine stress response; and earlier return of
      gastrointestinal function. Nonetheless, large multicenter prospective randomized
      studies are required to more definitively assess the impact of EAA on morbidity
      and mortality, ICU time, length of hospitalization, and cost of healthcare.

PMID- 10935018
TI  - Common nerve blocks in chronic pain management.
AB  - Anesthesiologists have become increasingly involved with the management of
      chronic pain patients in the operating room, on the surgical floor, and in the
      outpatient pain facility setting (often interdisciplinary). Based upon the
      authors' practice of regional anesthesia, the most specific contribution to
      chronic pain management arguably remains the practice of diagnostic, prognostic,
      and therapeutic injections of the neuraxis, peripheral nerves, and the autonomic
      nervous system.

PMID- 10935019
TI  - Complications of spinal and epidural anesthesia.
AB  - In conclusion, major complications after neuraxial techniques are rare but can be
      devastating to the patient and the anesthesiologist. Prevention and management
      begin during the preoperative visit with a careful evaluation of the patient's
      medical history and appropriate preoperative discussion of the risks and benefits
      of the available anesthetic techniques. Alternative anesthetic techniques, such
      as peripheral regional techniques or general anesthesia, should be considered for
      patients at increased risk for neurologic complications following neuraxial
      block. The decision to perform a regional anesthetic technique on an anesthetized
      patient must be made with care, as these patients are unable to report pain on
      needle placement or injection of local anesthetic. Efforts should also be made to
      decrease neural injury in the operating room through careful patient positioning.
      Postoperatively, patients must be followed closely to detect potentially
      treatable sources of neurologic injury, including expanding spinal hematoma or
      epidural abscess, constrictive dressings, improperly applied casts, and increased
      pressure on neurologically vulnerable sites. New neurologic deficits should be
      evaluated promptly by a neurologist, or neurosurgeon, to document formally the
      patient's evolving neurologic status, arrange further testing or intervention,
      and provide long-term follow-up.

PMID- 10935020
TI  - Mammary gland development and tumorigenesis in estrogen receptor knockout mice.
AB  - Estrogens are important for the development of the mammary gland and strongly
      associated with oncogenesis in this tissue. The biological effects of estrogens
      are mediated through the estrogen receptor (ER), a member of the nuclear receptor
      superfamily. The estrogen/ER signaling pathway plays a central role in mammary
      gland development, regulating the expression and activity of other growth factors
      and their receptors. The generation of the ER knockout (ERKO) mouse has made it
      possible to directly understand the contribution of ER in mammary development and
      has provided an unique opportunity to study estrogen action in carcinogenesis. A
      mammary oncogene (Wnt-1) was introduced into the ERKO background to determine if
      the absence of the ER would affect the development of tumors induced by oncogenic
      stimulation. The development, hyperplasia, and tumorigenesis in mammary glands
      from the ERKO/Wnt-1 mouse line are described. These studies provide the impetus
      to evaluate the effect of other oncogenes in mammary tumorigenesis in the absence
      of estrogen/ER signaling.

PMID- 10935021
TI  - A specific role for cyclin D1 in mammary gland development.
AB  - Cyclin D1 is a critical component of the core cell cycle machinery. Mice lacking
      cyclin D1 develop mammary glands that fail to undergo normal lobuloalveolar
      proliferation during pregnancy. Thus, cyclin D1 seems to play a critical role in
      pregnancy-induced proliferation of mammary epithelium. Cyclin D1 also
      participates in neoplasia, as the majority of human mammary carcinomas contain
      elevated levels of this cyclin.

PMID- 10935022
TI  - Use of PRKO mice to study the role of progesterone in mammary gland development.
AB  - To better understand the distinct physiological roles played by progesterone and
      estrogen receptors (PR and ER) as well as to study directly PR function in an in
      vivo context, a novel mutant mouse strain, the PR knockout (PRKO) mouse, was
      generated carrying a germline loss of function mutation at the PR locus. Mouse
      mammary gland development has been examined in PRKO mice using reciprocal
      transplantation experiments to investigate the effects of the stromal and
      epithelial PRs on ductal and lobuloalveolar development. The absence of PR in
      transplanted donor epithelium, but not in recipient stroma, prevented normal
      lobuloalveolar development in response to estrogen and progesterone treatment.
      Conversely, the presence of PR in the transplanted donor epithelium, but not in
      the recipient stroma, revealed that PR in the stroma may be necessary for ductal
      development. Stimulation of ductal development by the PR may, therefore, be
      mediated by an unknown secondary signaling molecule, possibly a growth factor.
      The continued stimulation of the stromal PR appears to be dependent on reciprocal
      signal(s) from the epithelium. Thus, the combination of gene knockout and
      reciprocal transplantation technologies has provided some new insights into the
      role of stromal-epithelial interactions and steroid hormones in mammary gland
      development.

PMID- 10935023
TI  - Mammary gland development in prolactin receptor knockout mice.
AB  - A germ line null mutation of the prolactin receptor gene has been produced by
      replacing exon 5 with the Tk-NEO cassette. Heterozygous females showed almost
      complete failure of lactation following their first pregnancy when mated at 6-8
      weeks of age. The severity of this phenotype was reduced when heterozygotes were
      mated at 20 weeks and was absent following a second pregnancy when assessed by
      pup survival, although a longer lag time prior to weight increase at normal rates
      was seen in these litters. Histological and whole mount analysis of virgin
      mammary glands showed that heterozygous glands were smaller in size due to a less
      developed ductal structure with fewer branch points. Virgin knockout glands were
      small, composed of sparse, large, poorly branched ducts. This work provides an
      ideal model to further study the role of the prolactin receptor and its ligands
      in mammary development and physiology.

PMID- 10935024
TI  - Developing a mammary gland is a stat affair.
AB  - The mammary gland is a recent acquisition on the phylogenetic scale of organ
      evolution and is characterized by an unparalleled regenerative capacity. With
      each pregnancy an expanded lobulo-alveolar compartment rises on the ductal
      compartment and differentiates to secrete large amounts of milk during lactation.
      After weaning of the young the entire alveolar compartment undergoes apoptosis
      and is remodeled to return to a virgin-like state. Evolution recruited old hands
      from existing signaling pathways to guide and accomplish the extraordinary task
      of repeatedly building and destroying this highly specialized tissue. Seventy
      years ago it was known that the presence of estrogen, progesterone, and prolactin
      (PRL) was essential for ductal and alveolar development. The recent ability to
      generate mice from which genes have been deleted by homologous recombination has
      made it possible to gain molecular insight into the signaling pathways used by
      these hormones to effect mammary differentiation. In the cast of characters
      progesterone and PRL are on center stage. After binding to its receptor, PRL
      activates the JAK-STAT pathway leading to transcription of genes which induce
      alveolar proliferation and differentiation. In vivo experiments have shown that
      JAK-Stat signaling is mandatory for adult mammary gland development and
      lactation. Two Stat molecules, Stat3 and Stat5, appear to have opposite functions
      and their relative activity may serve to control developmental cycles of mammary
      tissue. While Stat5 activity has been linked to alveolar proliferation and
      function, Stat3 activity correlates with the loss of alveolar function, cell
      death and the initiation of mammary tissue remodeling.

PMID- 10935025
TI  - Conditional control of gene expression in the mammary gland.
AB  - Identifying gene function during mammary gland development and function remains a
      technical challenge. For example, if a gene deletion is lethal during early
      embryogenesis, there is no opportunity to study its effects on the development or
      function of the gland. Similarly, if a dominant gain of gene function alters
      early mammary gland development, then its specific role during lactation cannot
      be assessed. Conditional gene expression systems can be used to circumvent these
      problems. Gene deletions or dominant gain experiments can be performed in an
      organ or cell type specific manner at specific timepoints using inducible gene
      expression systems. This review focuses on tetracycline responsive
      transactivation and Cre-lox systems. Other tetracycline regulatable (tet system)
      or hormone inducible systems and the Flp recombinase system are discussed as
      alternative approaches. Each system is described. The advantages and
      disadvantages of each for studying gene function in the mammary gland are
      discussed. Finally, the role of mammary gland transplantation in these genetic
      studies is examined.

PMID- 10935028
TI  - Readers question articles in support of complementary and alternative therapies.

PMID- 10935027
TI  - Elucidation of a role for stromal steroid hormone receptors in mammary gland
      growth and development using tissue recombinants.
AB  - The use of tissue recombinants in conjunction with steroid receptor deficient
      mice is described as a tool to dissect the complex paracrine pathways of sex
      hormone-regulated epithelial growth and ductal morphogenesis in the mammary gland
      and other hormone target organs. The basic methodology involves the construction
      of the four possible tissue recombinants composed of epithelium (E) and stroma
      (S) from wild-type (wt) and knock-out (KO) mice: wt-S + wt-S, wt-S + KO-E, KO-S +
      KO-E, and KO-S + wt-E. All tissue recombinants are grown as subrenal capsule
      grafts in nude mice. Following appropriate hormonal challenge epithelial growth
      can be studied in the four types of tissue recombinants. Such studies using
      estrogen receptor, androgen receptor and progesterone receptor knockout mice
      demonstrate that epithelial steroid receptors are neither necessary nor
      sufficient for hormonal regulation of epithelial proliferation. Instead, hormonal
      regulation of epithelial proliferation is a paracrine event mediated by hormone
      receptor-positive stromal cells.

PMID- 10935026
TI  - A role for fibroblast growth factor signaling in the lobuloalveolar development
      of the mammary gland.
AB  - The inappropriate expression of growth factors, or activating mutations of their
      receptors, have been implicated as causative factors in mouse and human mammary
      cancer. For example, it has been known for some time that three members of the
      fibroblast growth factor (FGF) family behave like oncogenes in virally induced
      mammary cancer of mice. In normal circumstances, signaling via FGF receptors is
      known to mediate growth, differentiation, and patterning, during embryogenesis
      and fetal development. A powerful approach to dissecting the roles for these
      signaling pathways is to determine the developmental consequences of abrogating
      their function in transgenic mice. In this review, we describe the use of
      dominant negative FGF receptors to evaluate the contribution of specific FGF
      signals in normal mammary gland development. These studies have revealed that
      normal lobuloalveolar development requires FGF signaling to the mammary
      epithelium, a function that is presumably usurped by MMTV in mouse mammary
      tumorigenesis.

PMID- 10935029
TI  - Readers question articles in support of complementary and alternative therapies.

PMID- 10935030
TI  - More thoughts on puppy mills and the pet industry.

PMID- 10935031
TI  - More thoughts on puppy mills and the pet industry.

PMID- 10935032
TI  - What is your diagnosis? A 4-cm mass protruding from the dorsal area of the
      cloaca.

PMID- 10935033
TI  - Changing demographics.

PMID- 10935034
TI  - Euthanasia--some legal aspects.

PMID- 10935035
TI  - Executive summary of the Brakke management and behavior study.

PMID- 10935036
TI  - Evaluation of treatments for separation anxiety in dogs.
AB  - OBJECTIVE: To evaluate treatment outcome in dogs with separation anxiety and
      owner compliance with and perception of effectiveness of discharge instructions.
      DESIGN: Cohort study. ANIMALS: 52 dogs with separation anxiety. PROCEDURE: Sex,
      age at which the owner obtained the dog, age at which separation anxiety was
      first noticed, age at behavioral examination, and discharge instructions were
      obtained from medical records of each dog. Between 6 and 64 months after the
      behavioral examination, owners were contacted by telephone and questioned about
      the outcome of treatment, their compliance with discharge instructions, and their
      perception of the effectiveness of each instruction. RESULTS: Thirty-two (62%)
      dogs had improved, whereas 20 were the same, were worse, or had been euthanatized
      or given away. Mixed-breed dogs were significantly less likely to improve than
      purebred dogs. Compliance varied according to discharge instruction.
      Significantly fewer dogs with owners that were given > 5 instructions improved or
      were cured, compared with those with owners given fewer instructions. Twenty
      seven dogs were also treated with amitriptyline or other medication; 15 (56%)
      improved. CONCLUSIONS AND CLINICAL RELEVANCE: Owners complied with instructions
      that involved little time such as omitting punishment and providing a chew toy at
      the time of departure. Owners were also willing to increase the dog's exercise
      but were not willing to uncouple the cues of departure from real departures or
      desensitize the dog to impending departure. Administration of psychoactive
      medication may be necessary to augment behavior modification techniques designed
      to reduce separation anxiety in dogs.

PMID- 10935037
TI  - Renal effects of carprofen administered to healthy dogs anesthetized with
      propofol and isoflurane.
AB  - OBJECTIVE: To evaluate renal effects of carprofen in healthy dogs following
      general anesthesia. DESIGN: Randomized clinical trial. ANIMALS: 10 English hound
      dogs (6 females and 4 males). PROCEDURE: Dogs were randomly assigned to control
      (n = 5) or carprofen (5) groups. Anesthesia was induced with propofol (6 to 8
      mg/kg [2.7 to 3.6 mg/lb] of body weight, i.v.) and maintained with isoflurane
      (end-tidal concentration, 2.0%). Each dog underwent two 60-minute anesthetic
      episodes with 1 week between episodes, and mean arterial blood pressure was
      maintained between 60 and 90 mm Hg during each episode. Dogs in the carprofen
      group received carprofen (2.2 mg/kg [1 mg/lb], p.o.) at 9:00 AM and 6:00 PM the
      day before and at 7:00 AM the day of the second anesthetic episode. Glomerular
      filtration rates (GFR) were determined during each anesthetic episode by use of
      renal scintigraphy. Serum creatinine and BUN concentrations and the urine gamma
      glutamyltransferase-to-creatinine concentration (urine GGT:creatinine) ratio were
      determined daily for 2 days before and 5 days after general anesthesia. RESULTS:
      Significant differences were not detected in BUN and serum creatinine
      concentrations, urine GGT:creatinine ratio, and GFR either between or within
      treatment groups over time. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen did not
      significantly alter renal function in healthy dogs anesthetized with propofol and
      isoflurane. These results suggest that carprofen may be safe to use for
      preemptive perioperative analgesia, provided that normal cardiorespiratory
      function is maintained.

PMID- 10935038
TI  - Use of an external skin-stretching device for wound closure in dogs and cats.
AB  - Use of an externally applied, noninvasive skin-stretching device in 24 dogs and
      cats is described. The device uses adhesive-coated pads that are applied to the
      skin of an animal; pads are positioned on opposite sides of a surgical site and
      are connected by means of adjustable elastic cables. The cables maintain
      continuous tension, and cable tension is adjusted and progressively increased at
      intervals of 6 to 8 hours to promote skin recruitment (stretching), using the
      cutaneous viscoelastic properties of mechanical creep and stress relaxation.
      Consequently, skin adjacent and distant to the surgical site can be recruited to
      facilitate wound closure, typically within 72 to 96 hours after application of
      the device. The skin-stretching device has been used effectively in dogs and cats
      to stretch skin prior to elective surgical procedures, stretch skin during
      management of open wounds prior to suturing, and alleviate incisional tension
      after surgery.

PMID- 10935039
TI  - Heartworm infection in cats: 50 cases (1985-1997).
AB  - OBJECTIVE: To characterize risk factors, clinical findings, usefulness of
      diagnostic tests, and prognosis in cats with naturally occurring heartworm
      infection (HWI). DESIGN: Retrospective study. ANIMALS: 50 cats with Dirofilaria
      immitis infection. PROCEDURE: Medical records, thoracic radiographs, and
      echocardiograms were reviewed and findings compared with appropriate reference
      populations. RESULTS: Findings suggested that male cats were not predisposed to
      HWI, domestic shorthair cats were at increased risk, and indoor housing was only
      partially protective. Fewer cases of HWI were identified in the final quarter of
      the year, compared with other periods, and prevalence is not apparently
      increasing. Signs of respiratory tract disease were most common, followed by
      vomiting. Infection was diagnosed incidentally in > 25% of cats; conversely, 10%
      of infected cats died suddenly without other clinical signs. Serologic tests were
      most useful for diagnosis, followed by radiography and echocardiography.
      Eosinophilia supported the diagnosis. Overall median survival time was 1.5 years
      but exceeded 4 years in cats surviving beyond the day of diagnosis. CONCLUSIONS
      AND CLINICAL RELEVANCE: Sex does not appear to be a risk factor for HWI in cats,
      and indoor housing provides only incomplete protection. Signs of respiratory
      tract disease (dyspnea and cough) are the strongest indicators of HWI in cats,
      and some radiographic evidence of infection is detected in most cases. Antibody
      screening for HWI in cats is efficacious, and antigen testing and
      echocardiography are most useful for making a definitive antemortem diagnosis.

PMID- 10935040
TI  - Pulmonary function and adrenal gland suppression with incremental doses of
      aerosolized beclomethasone dipropionate in horses with recurrent airway
      obstruction.
AB  - OBJECTIVE: To evaluate clinical response, pulmonary function, and adrenal gland
      response to incremental doses of beclomethasone dipropionate in horses with
      recurrent airway obstruction. DESIGN: Crossover trial. ANIMALS: 8 horses with
      recurrent airway obstruction. PROCEDURE: Horses randomly assigned to 4 groups
      were treated twice daily via aerosol administration of placebo or 500, 1,000, or
      1,500 micrograms of beclomethasone dipropionate in a crossover design with a 10
      day minimum washout period. Subjective assessment of airway obstruction, serum
      cortisol concentration, and maximum change in pleural pressure during tidal
      breathing (delta Pplmax) were determined daily prior to morning drug
      administration, and delta Pplmax was reevaluated 15 minutes after morning drug
      administration. Pulmonary resistance and dynamic compliance were determined at
      baseline and approximately 12 hours after the final treatment. RESULTS: An
      immediate treatment effect was not identified. Within 24 hours, delta Pplmax and
      airway obstruction were lower in horses receiving beclomethasone. Onset and
      magnitude of response was similar among the 3 beclomethasone dose regimens.
      Pulmonary resistance was improved only after administration of all 3 doses of
      beclomethasone, whereas dynamic compliance was improved after administration of
      1,000 micrograms and 1,500 micrograms of beclomethasone. Reduction in serum
      cortisol concentration occurred with all 3 beclomethasone dose regimens; however,
      the magnitude of adrenal gland suppression was greater in horses receiving 1,000
      or 1,500 micrograms of beclomethasone. CONCLUSIONS AND CLINICAL RELEVANCE: Low
      dose (500 micrograms) beclomethasone administration caused similar, improvement
      in pulmonary function, compared with high-dose beclomethasone (1,000 and 1,500
      micrograms), with the exception of dynamic compliance, and caused less
      suppression of endogenous cortisol production.

PMID- 10935041
TI  - An outbreak of type C botulism in 12 horses and a mule.
AB  - A USDA Early Response Team investigated deaths of several horses and a mule in
      northern Arizona at the request of local animal health officials. Thirteen
      animals (12 horses and 1 mule) housed at 5 facilities in a 7.4 square mile area
      died between August 1998 and January 1999. Clinical signs consisted of muscular
      weakness that rapidly progressed to lateral recumbency. Ten animals had paresis
      of the tongue, throat, or lips. Affected animals appeared alert and were
      interested in eating and drinking, even while recumbent. All 13 animals were
      euthanatized. Clostridium botulinum type C was isolated from feces or intestinal
      contents from 3 affected horses. Preformed toxin was detected in samples of soil
      and bird droppings collected from a nearby horse burial site. It was hypothesized
      that the outbreak was a result of birds, presumably ravens, feeding at the burial
      site and at horse facilities in the area that transferred toxin to the affected
      animals.

PMID- 10935042
TI  - Antibiotic residues in milk following bulbar subconjunctival injection of
      procaine penicillin G in dairy cows.
AB  - OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a
      concentration that is detectable following bulbar subconjunctival injection in
      lactating dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 66 Holstein
      cows that were at least 2 weeks past calving and had not been treated with
      antibiotics in the preceding 30 days. PROCEDURE: Cows were randomly assigned to
      receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar
      subconjunctival injection or remain untreated. Composite milk samples were
      collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after
      treatment. Milk samples were tested by use of a commercial test for beta-lactam
      antibiotics. RESULTS: Among penicillin-treated cows, the first positive test
      results were observed 4 hours after treatment, and the last positive result was
      observed 22 hours after treatment. The percentages of positive test results
      before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0,
      9, 87, 42, 8, 0, and 0%, respectively. None of the untreated cows had positive
      test results for beta-lactam antibiotics at any sampling time. CONCLUSIONS AND
      CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a
      single subconjunctival injection of procaine penicillin G in cows. This result
      should be considered when recommending milk withholding periods following the
      administration of penicillin by this route in lactating dairy cows.

PMID- 10935043
TI  - Secondary lactose intolerance in a neonatal goat.
AB  - A 2-week-old Toggenburg kid was evaluated for persistent diarrhea and poor body
      condition. The herd had high morbidity and mortality associated with diarrhea in
      neonatal kids. Lactose intolerance was diagnosed on the basis of results of a
      lactose tolerance test and glucose absorption test. Clinically normal herdmates
      were used as control animals. The kid responded to lactase supplementation.
      Cryptosporidium organisms were detected in feces of several affected kids during
      episodes of acute diarrhea. Lactose intolerance was presumed to have developed
      secondary to intestinal cryptosporidiosis.

PMID- 10935044
TI  - Osseous sequestration in cattle: 110 cases (1987-1997).
AB  - OBJECTIVE: To determine risk factors for development of sequestra in cattle and
      identify factors associated with a successful outcome. DESIGN: Retrospective
      study. ANIMALS: 110 cattle. PROCEDURE: Medical records of cattle treated at
      veterinary teaching hospitals in North America were reviewed. To determine risk
      factors for osseous sequestration, breed, age, and sex of cattle with osseous
      sequestration were compared with breed, age, and sex of all other cattle admitted
      during the study period. RESULTS: 110 cattle were included in the study. Three
      had 2 sequestra; thus, 113 lesions were identified. Most sequestra were
      associated with the bones of the extremities, most commonly the third metacarpal
      or third metatarsal bone. Ninety-two animals were treated surgically (i.e.,
      sequestrectomy), 7 were treated medically, 3 were initially treated medically and
      were then treated surgically, and 8 were not treated. Follow-up information was
      available for 65 animals treated surgically and 6 animals treated medically.
      Fifty-one (78%) animals treated surgically and 5 animals treated medically had a
      successful outcome. Cattle that were 6 months to 2 years old had a significantly
      increased risk of developing a sequestrum, compared with cattle < 6 months old.
      Cattle in which sequestrectomy was performed with the aid of local anesthesia
      were significantly more likely to undergo 2 or more surgical procedures than were
      cattle in which sequestrectomy was performed with the aid of general anesthesia.
      CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that sequestrectomy will
      result in a successful outcome for most cattle with osseous sequestration.

PMID- 10935046
TI  - The public-sector safety net for HIV-related care.

PMID- 10935045
TI  - T-cell lymphoproliferative disorder in an aged rhesus macaque.
AB  - A CD8+ T-cell leukemia was diagnosed in an aged female rhesus macaque. Although
      leukemia and lymphoma in nonhuman primates are commonly associated with simian T
      lymphotropic virus, gibbon ape leukemia virus, oncogenic herpesviruses, and types
      C, D, and E retroviruses, this monkey was not infected with any of these viruses.
      However, the monkey did have antibodies against herpesvirus saimiri. This likely
      represents cross-reactivity of the herpesvirus saimiri assay with rhesus monkey
      rhadinovirus (RRV) antibodies; RRV was first described in rhesus macaques that
      were identified as having antibodies against herpesvirus saimiri. Rhesus
      rhadinovirus is a gamma herpesvirus, related antigenically to herpesvirus saimiri
      and Kaposi's sarcoma-associated herpesvirus (KSHV), which have been linked to
      lymphoproliferative disorders in primates and humans, respectively. Moreover, an
      oncogene has been recently identified in the RRV genome that is equivalent in
      position to the herpesvirus saimiri and KSHV oncogenes. Presently, the
      association of RRV infection with disease in nonhuman primates is unknown.

PMID- 10935047
TI  - Social norms and the evolution of drug regulation in the U.S.: implications for
      access to medications for HIV disease.

PMID- 10935048
TI  - To treat or not to treat: the ethical dilemma of alternative medicine therapies.

PMID- 10935049
TI  - Lactic acidosis associated with nucleoside analog therapy in an HIV-positive
      patient.
AB  - A 44-year-old African-American female, HIV positive treated with highly active
      antiretroviral therapy (HAART), consisting of two nucleoside analogues and one
      nonnucleoside reverse transcriptase inhibitor, who was initially admitted with
      severe lactic acidosis. Liver biopsy was performed on the ninth hospital day,
      which revealed moderate microvesicular and macrovesicular fatty changes. The
      possible mechanism of lactic acidosis in patients on nucleoside analogues is
      discussed. The question as to how to monitor for this syndrome, as usual tests
      are neither sensitive nor specific, still remains important.

PMID- 10935050
TI  - Effect of highly active antiretroviral therapy on the incidence of HIV-related
      cytomegalovirus retinitis and retinal detachment.
AB  - Cytomegalovirus retinitis (CMVR) is the most common intraocular infection
      encountered in ophthalmic practices. To assess the impact of highly active
      antiretroviral therapy (HAART) on the incidence of CMVR and subsequent retinal
      detachments, a retrospective review of the HIV+ patients seen at a single
      university and community-based practice between 1992-1993 (group 1), before the
      advent of protease inhibitors, was compared with the data obtained from October
      1996 to October 1997 (group 2) and October 1997-1998 (group 3), after the
      widespread use of HAART. The incidence of CMVR and retinal detachment rates for
      each group was calculated and compared. Twenty five (2.6%) of 974 HIV+ patients
      in group 1 developed CMVR. Of these, four patients developed retinal detachment
      (16%). Group 2 had a total of 1084 HIV+ patients, 18 (1.7%) of whom developed
      CMVR, which indicates a 35% decline of the incidence of CMV retinitis at our
      institution (p = 0.052, Odds ratio = 0.533, Confidence interval 0.28-1.01) and
      three patients (20%) developed retinal detachment. Only 1 patient (0.07%) of 1274
      patients in group 3 developed CMVR, which represents a 99% reduction since 1993
      (p = 0.0000000456). We conclude that the incidence of CMVR at this institution
      has decreased significantly with the recent use of HAART therapy. This effect may
      be related to the aggressive use of HAART and associated immune recovery in this
      population of AIDS patients. In this small series, however, the rate of retinal
      detachment appeared unchanged, but was only observed in those individuals who
      were not on HAART or who had just recently started.

PMID- 10935051
TI  - Evaluation of patient satisfaction in a specialized HIV/AIDS care unit of a major
      hospital.
AB  - Patient satisfaction has gained widespread recognition as an important indicator
      of quality of care. In this study, we analyzed quality of care in correlation
      with patient satisfaction. Our results indicate that the overall satisfaction of
      quality of care of HIV/AIDS patients in a dedicated HIV/AIDS unit is affected
      mainly by the patient's perception of his/her health status, level of
      professional or family support, and the patient's level of involvement in
      treatment decisions.

PMID- 10935052
TI  - Antiretroviral medication adherence and persistence with respect to adherence
      tool usage.
AB  - Adherence to complex drug regimens over an extended period is a key factor in
      reaping the health benefits of highly active antiretroviral therapy (HAART).
      Forgetting a dose is the most commonly stated reason for suboptimal adherence,
      indicating a potential benefit of reminder devices. We examined antiretroviral
      drug adherence and duration of therapy with respect to adherence tool usage.
      Adherence was monitored for 12 months in a cohort of patients, using pharmacy
      refill data. Seventy-eight subjects were administered a questionnaire with regard
      to tool use at least once at 6 and/or 12 months; patients who replied to the
      questionnaire were eligible for this study. Persistence of remaining on therapy
      was obtained from the subjects, charts. The tools included individualized
      schedules, dosettes and electronic reminder devices, which were offered free of
      charge to all patients. Of the 64 subjects who entered this study, 60.9% (n = 39)
      used at least one adherence tool. The median adherence in those using tools was
      95%; three quarters showed greater than 91% adherence. Adherence rates with
      respect to individual tools did not differ significantly for schedules and
      dosettes, with medians of 95% (n = 31) and 94% (n = 13), respectively. Median
      adherence with electronic reminders was 76% (n = 5). Seventy-four percent of
      patients remained on therapy after 12 months of study. Taking into consideration
      previous antiretroviral treatment, actual persistence at 12 months was 87%.
      Employing and individualizing strategies, including adherence tools, to enhance
      patient adherence to complex regimens in addition to counseling and follow-up,
      has resulted in good adherence rates and persistence.

PMID- 10935053
TI  - Service use patterns of youth with, and at high risk for, HIV: a care typology.
AB  - This paper uses confirmatory structural equation models to develop and test a
      theoretical model for understanding the service utilization history of 4679 youth
      who received services from 10 national HIV/AIDS demonstration models of youth
      appropriate and youth-attractive services funded by the Special Projects of
      National Significance (SPNS) Program, HIV/AIDS Bureau, Health Resources and
      Services Administration. Although the projects differ from one another in the
      areas of emphasis in their service models, each is targeted to youth at high risk
      for HIV, or those youth who have already contracted HIV. Collectively, the
      projects represent a comprehensive adolescent HIV service model. This paper
      examines the characteristics of the services provided to young people ranging
      from outreach to intensive participation in medical treatment. Major typologies
      of service utilization are derived empirically through exploratory factor and
      cluster analysis methods. Confirmatory structural equation modeling methods are
      used to refine the exploratory results using a derivation and replication
      strategy and methods of statistical estimation appropriate for non-normally
      distributed service utilization indicators. The model hypothesizes that youth
      enter the service system through a general construct of connectedness to a
      comprehensive service model and through service-specific methods, primarily of
      outreach or emergency services. Estimates are made of the degree to which a
      comprehensive service model drives the services as opposed to specific service
      entry points.

PMID- 10935054
TI  - Change in perceived barriers and facilitators to treatment among women with
      HIV/AIDS as a function of psychosocial service utilization.
AB  - Using a repeated assessment of 185 women with HIV in three national service
      demonstration projects that focus on reducing barriers to care, self-reported
      barriers to obtaining services decreased significantly over time. At the earliest
      time asked, participants scored an average of 5.23 on a measure of barriers to
      obtaining care. At the most recent time asked, they scored an average of 4.05 on
      the barrier measure. In a subsample of 122 women with HIV, it was found that self
      reported facilitators to obtaining services increased significantly over time. At
      the first time asked, participants scored an average of 8.40 on a measure of
      facilitators to receiving services. At the most recent time asked, they scored an
      average of 8.98 on the facilitator measure. Results are discussed in terms of
      implications for designing services to minimize barriers and maximize
      facilitators to care for people living with HIV/AIDS.

PMID- 10935055
TI  - HIV/AIDS case histories: acute HIV infection.

PMID- 10935056
TI  - Mutation causes sensitivity.

PMID- 10935057
TI  - Europe warned of side effects.

PMID- 10935058
TI  - Promising results for tenofovir.

PMID- 10935059
TI  - Many unaware of herpes risk.

PMID- 10935060
TI  - Sponge approval sought.

PMID- 10935061
TI  - Octasodium hexatungstomanganate(IV) octadecahydrate

PMID- 10935062
TI  - The structures of the alpha-alums RbCr(SO4)2.12H2O and CsCr(SeO4)2.12H2O at 293
      and 12 K

PMID- 10935064
TI  - K2TiSi3O9.H2O

PMID- 10935063
TI  - Cs2K

PMID- 10935067
TI  - NiII and ZnII complexes of the hexadentate macrocyclic ligand cis-6, 13-dimethyl
      1,4,8,11-tetraazacyclotetradecane-6,13-diamine

PMID- 10935065
TI  - (NH4)4Na2

PMID- 10935066
TI  - Bis(2-aminopyridine-N)bis(benzoato-O)zinc.

PMID- 10935068
TI  - Di-mu-isopropoxy-bis

PMID- 10935070
TI  - cis-Dichloro(5,8-dioxa-2,11-dithia-

PMID- 10935069
TI  - Polymorphs and pseudo-polymorphs of mu-oxo-bis

PMID- 10935071
TI  - Hydrido-sulfido-bridged triangular Os3 cluster compounds with different phosphine
      ligand substitution patterns

PMID- 10935072
TI  - Adducts of nickel(II) acetylacetonate chelating with heterocyclic bases: 3
      cyanopyridine and 4-cyanopyridine

PMID- 10935073
TI  - Aqua(5,6-dimethyl-1,10-phenanthroline-N,N')(glycolato-O,O')copper(II) nitrate

PMID- 10935074
TI  - [1,5-Bis]

PMID- 10935075
TI  - Three new ZnII sulfate complexes

PMID- 10935077
TI  - Transition metal complexes with pyrazole-derived ligands. XI.

PMID- 10935076
TI  - trans-Bis(thioacetato-S)bis(triphenylphosphine-P)nickel(II)

PMID- 10935078
TI  - A 4-ethylpyridine complex of tetrachloromolybdenum(III) and its oxidation product

PMID- 10935079
TI  - Ni(bipy)2Ni(CN)4, a new type of one-dimensional square tetracyano complex

PMID- 10935081
TI  - Polymeric aqua(glutarato)(hydrogen glutarato)lanthanum(III) monohydrate

PMID- 10935080
TI  - catena-Poly

PMID- 10935082
TI  - Layered zincoarsenate templated by N,N,N',N'-tetramethylethylenediamine molecules

PMID- 10935083
TI  - The lithium chloride complex of the anti isomer of the bridged spherand C50H48O6.

PMID- 10935084
TI  - 1,2-Dicyano-1,2-bis(imidazolidine-2-thione)digold(I) and 2,2-dicyano-1,1
      bis(dimethylthiourea)digold(I)

PMID- 10935085
TI  - Diiodobis(1-methyl-1,3-imidazolium-2-thiolato-S)mercury(II)

PMID- 10935086
TI  - Hydrolysis products of diorganotin dihalides. I. Bis

PMID- 10935087
TI  - Diiodobis(4-methylpentan-2-onato-C4,O)tin(IV): a comparison with diiodobis(3
      methoxy-3-oxopropyl-C,O)tin(IV)

PMID- 10935089
TI  - catena-Poly

PMID- 10935088
TI  - Pyridine-pyridine pi-pi stacking interactions in pentacarbonyl[pyridine-4(1H)
      thione]tungsten(0).

PMID- 10935090
TI  - Tetraallyl (2,2'-bipyridyl)-rac-3,3,7,7-tetramethyl-trans-5- palladatricyclo-

PMID- 10935091
TI  - Lithium phosphoenolpyruvate monohydrate at 85 K.

PMID- 10935092
TI  - (S)-tricarbonyl

PMID- 10935093
TI  - mu-Glycine-O:O'-di-mu-oxo-bis[(glycinato-N,O)oxomolybdenum(V)].

PMID- 10935094
TI  - 6,7-Dihydrodibenzo[e,g]azulen-8(5H)-one and 12,13-dihydrobenzo[e]napth[2,1
      g]azulen-14(11H)-one.

PMID- 10935095
TI  - 2,3,3a,4,9,9a-hexahydro-9-phenylbenzo

PMID- 10935096
TI  - (3R*,3'R*)-1,1'-dimethyl-3,3'-biindoline-2,2'-dithione

PMID- 10935097
TI  - 3,5-Dimethyl-6-(4-nitroanilino)-2,3,4,5-tetrahydro-1,3,5-triazine-2,4- dione,
      (II), 3,5-dimethyl-6-(N-methyl-4-nitroanilino)-2,3,4,5-tetrahydro-1,3,5-triazine-
      2,4-dione, (III), and 1,3,5-trimethyl-6-(4-nitrophenylimino)-1,3,5-triazinane-2,4
      dione, (IV)

PMID- 10935098
TI  - []

PMID- 10935099
TI  - 2-

PMID- 10935100
TI  - 7-Chloro-3,6-dimethyl-1H-indene-2-carbaldehyde

PMID- 10935102
TI  - 4,8-Dimethoxy-1-naphthalenemethanol

PMID- 10935101
TI  - Hydrogen bonds and C-H...O interactions in the enol tautomer of 4
      (phenylsulfonyl)spiro[cyclopentane-1,9'-[9H]fluorene]-2,3-dione.

PMID- 10935103
TI  - (3R*,4R*)-3-isopropyl-4-phenylazetidin-2-one at 150 K

PMID- 10935104
TI  - Hydrogen bonding and C-H...X interactions in 3-fluoro-2-[1-(1
      naphthyl)ethyl]benzoic acid.

PMID- 10935105
TI  - Hydrogen bonds and C-H...O interactions in 2-(2-methylbenzyl)malonic acid at 150
      K

PMID- 10935106
TI  - A structural hierarchy in the hydrogen-bonded adduct ethane-1,2-diphosphonic acid
      4,4'-bipyridyl-water (1/1/2): an N-component N-dimensional structure (N = 3) with
      substructures having N = 1 and 2

PMID- 10935107
TI  - Chains of fused rings in the hydrogen-bonded structure of meso-6,13-diamino-6,13
      dimethyl-1,4,8,11-tetraazacyclotetradecane-2,2'- biphenol (1/2)

PMID- 10935108
TI  - Hydrogen-bonded molecular ladders in 1,4-bis(4-chlorophenylsulfonyl)-2,5
      dimethylbenzene

PMID- 10935109
TI  - Hydrogen-bonded molecular ladders in trans-1,2-bis(2-nitroanilino)cyclohexane

PMID- 10935110
TI  - 21 alpha-fluoro-7-norvouacapane-17 beta,21 alpha-lactone.

PMID- 10935111
TI  - 2,6-Diphenylthiapyran-4-one

PMID- 10935112
TI  - 6-Amino-5,5,7-tricyano-3,3a,4,5-tetrahydro-2H-indene-4-spirocyclopentane

PMID- 10935113
TI  - N-H...pi hydrogen bonding in 2-aminofluorene

PMID- 10935114
TI  - S-H...S hydrogen-bond chain in thiosalicylic acid

PMID- 10935115
TI  - Tetrabutylammonium alpha-acetyl-gamma-butyrolactonate containing a three
      dimensional hydrogen-bonded network

PMID- 10935117
TI  - Red, orange and yellow crystals of 4,5-bis(4-methoxyphenyl)-2-(3-nitrophenyl)-1H
      imidazole

PMID- 10935116
TI  - Dimethyl 9,10-anthracenedicarboxylate: a centrosymmetric transoid molecule

PMID- 10935118
TI  - 1,1,3,3-Tetramethylguanidinium dihydrogenorthophosphate

PMID- 10935119
TI  - Methyl 1-

PMID- 10935120
TI  - p-Phenylazoaniline hydrochloride from powder data: protonation site and UV
      visible spectra

PMID- 10935122
TI  - Benzyltriethylammonium 2,2,2,4-tetrachloro-2,5-dihydro-1,2 lambda 5-oxa-tellurole

PMID- 10935121
TI  - 4-Phenyl-3,5-bis(2-pyridyl)-4H-1,2,4-triazole.

PMID- 10935123
TI  - 6-Hydroxy-2,2-dimethyl-3,4-dihydro-2H-benzo[b]pyran.

PMID- 10935124
TI  - NEt4OH.4H2O containing infinite hydroxide-water ribbons

PMID- 10935125
TI  - 1,15-Pentadecanediol

PMID- 10935126
TI  - A pentaerythritol-derived spirodiphosphonate

PMID- 10935127
TI  - Verticine ethanol hydrate (2/1/1).

PMID- 10935128
TI  - Pefloxacinium methanesulfonate 0.10-hydrate.

PMID- 10935129
TI  - Corneal transplantation in children.
AB  - Authors discuss the special problems related to childhood keratoplasties. They
      evaluate the results of the keratoplasties carried out in children during the
      past 10 years in their service. They review the concerning literature and
      summarize their opinion on the corneal transplantations of this age group.

PMID- 10935130
TI  - An unusual pulmonary perforation case after chest tube placement.
AB  - Pulmonary laceration is an uncommon complication of tube thoracostomy technique
      that is expected vigorous clinically and may be fatal. In this study, we report a
      case of pulmonary laceration owing to a tube thoracostomy, with no clinical
      signs, and detected incidentally on thorax computed tomography.

PMID- 10935131
TI  - Relationship between the survival and the clinicopathological parameters of the
      patients with tumors in the pancreatic head region.
AB  - Retrospective study was performed to assess the possible prognostic factors for
      survival in patients after radical surgery with carcinoma of the pancreatic head
      region. Twenty-nine patients underwent pancreaticoduodenectomy for cancers of the
      pancreatic head (n = 22) and the papilla of Vater (n = 7). Using flow cytometry,
      authors measured the nuclear DNA content of tumor cells. DNA ploidy status was
      evaluated from paraffin-embedded tumor tissues. Fourteen DNA diploid and eight
      DNA-aneuploid pancreatic carcinomas occurred. Six DNA diploid and one DNA
      aneuploid tumors were diagnosed in the group of papilla of Vater. Mean survival
      of patients with the carcinoma of pancreatic head was 9.3 months. Survival of the
      patients with the cancer of papilla of Vater was 20.5 months. The mean survival
      was 10 months in case of DNA-diploid pancreatic carcinoma, and it was 8 months in
      case of DNA-aneuploid cancer. The survival of the patients with DNA* diploid
      Vater papilla tumor was 17 months, and it was 40 months with the DNA-aneuploid
      cancer. The mean proliferative index (PI) of DNA-diploid pancreatic cancers was
      9.7%, whereas that of the DNA-aneuploid cases was 13.3%. The mean PI of DNA
      diploid tumors of papilla of Vater was 7.5% and that of the DNA aneuploid cases
      was 28%. There was no significant correlation between the PI and the survival.
      DNA-ploidy status and PI had no significant effect on the survival in patients
      with carcinoma of the pancreatic head region.

PMID- 10935132
TI  - Surgically treated Hashimoto's thyroiditis.
AB  - The primary way to treat Hashimoto's thyroiditis is conservative. However, it has
      a relatively high occurrence in operated patients, up to 13% in the literature.
      Indications for surgery are suspicion of malignancy, and/or trachea/esophagus
      compression. 2818 thyroid operations were performed at our department between
      1986 and 1995. 279 patients suffered from thyroid cancer and 2539 had benign
      disease. Histology revealed Hashimoto's thyroiditis in 118 cases. Coexisting
      malignant thyroid tumor was found in 14 cases (11.8%): 9 papillary, 2 follicular,
      1 anaplastic cancer, and 2 non-Hodgkin lymphoma. Postoperative recurrent
      laryngeal nerve paralysis occurred in 8 cases, of which 6 remained permanent.
      This relatively high incidence supports the importance to identify the laryngeal
      nerve during every operation for Hashimoto's thyroiditis. Four patients had
      temporary and one had permanent hypoparathyroidism. Coexistence of Hashimoto's
      thyroiditis and thyroid carcinoma, the increased risk for the development of non
      Hodgkin's lymphoma in chronic lymphocytic thyroiditis and the need for thyroxin
      supplementation in many cases justify a careful, long-term follow-up of patients
      with Hashimoto's disease.

PMID- 10935133
TI  - Fibro-osseous lesion of rib.
AB  - A 3 x 4 cm homogeneous opacity was incidentally detected over the first rib at
      routine chest radiography. Radionuclide bone scan identified a hot spot, not
      excluding malignancy and excision of the rib revealed fibro-osseous lesion. A
      review of the literature showed 12 cases of this extremely rare lesion.

PMID- 10935134
TI  - Eosinophilic cystitis in view of two cases.
AB  - Authors present their experiences with eosinophilic cystitis. In both of their
      cases the preoperative evaluation presumed bladder cancer, the histologic
      examination, however, showed eosinophilic cystitis. In this report a discussion
      is given on the diagnostic and treatment possibilities of the entity.

PMID- 10935136
TI  - Clinical nutrition in liver and pancreatic diseases.
AB  - According to international and national surveys, 5-15% of patients admitted to
      hospitals require partial or total artificial nutrition. The development or
      progression of malnutrition influences patients' lives significantly and also
      increases the costs of their treatment substantially and unnecessarily. Nutrition
      therapy, meaning a balanced intake of food or provision of nutrients, is an
      essential part of the critically ill patient's care. The proper concern of
      physicians today is not whether nutritional support is indicated in hepatic and
      pancreatic diseases, but when and how it should be given. Author, therefore,
      gives guidelines to the nutritional therapy of patients suffering from liver and
      pancreatic diseases since their metabolic support still remains the most
      challenging problems in clinical nutrition.

PMID- 10935135
TI  - Two cases of benign tracheo-gastric fistula following esophagectomy for cancer.
AB  - Two successfully managed cases of esophageal replacement for cancer complicated
      by neoesophagotracheal fistula are described. In both cases radical esophagectomy
      with a gastric pull-up was performed. In the postoperative period different
      complications necessitated prolonged ventilatory support and tracheostomy. In
      both cases a tracheo-gastric fistula developed probably because of the ischaemic
      effort of the tracheostomy tube and the nasogastric tube. At single stage
      repairs, the fistulae were divided and the gastric defects were closed directly.
      In the first case resection of four strictured tracheal rings and tracheal
      anastomosis had to be performed. In the second case the fistula was recognized
      earlier and stricture did not develop. The defect on the membranous trachea was
      patched with autologous fascia lata graft. A left pectoralis major muscle flap
      was interposed between the trachea and the pulled up stomach in both cases to
      prevent recurrence of the fistula. Treatment of this potentially life-threatening
      and rare condition yielded excellent results.

PMID- 10935137
TI  - Testicular biopsy helping assisted reproduction.
AB  - Authors have performed testis biopsy on 21 male patients according to the
      predesigned protocol. The biopsy has been carried out from scrotal excision, with
      the exposure of both testis with microsurgical method. The results have been
      evaluated according to the spermogram groups. Correlation of FSH values and
      histological appearance of both testis was analyzed. Their method and experiences
      have been evaluated the effectiveness of assisted reproduction.

PMID- 10935138
TI  - A case of a calcified renal cyst.
AB  - Authors review a case of a calcified renal cyst. The literary data at hand give
      evidence that the spreading processes in the kidney can be benign or malignant
      according to their form of calcification and their localisation. Despite the
      modern diagnostic techniques, it is not easy to set up the diagnosis or to avoid
      the need for surgery, as was the case in the present report.

PMID- 10935139
TI  - Anatomic variations in patients operated for bladder substitution.
AB  - Authors review the anatomic variations observed throughout orthotopic ileal
      neobladder formation in 38 cases following radical cystectomy. A part of the
      variations was necessitated because of deviation from the classic Hautmann-type
      surgical technique: in 6 cases the site of ileal resection was modified due to
      abnormal mesenterial art. course, on 2 occasions Meckel diverticules were
      detected while cutting the ileal neobladder, in 13 cases the laterally adhered
      sigma bladder necessitated the left-sided ureter to be pulled through beneath the
      mesosigma for the purpose of making sure the ureter--ileal neobladder anastomosis
      became free of any tension, while on 1 occasion the left ureteral preparations
      went with some injury. Since the left ureter became short, ureter replacement
      variation was needed, similar to the Studer method of ileal neobladder formation.
      All these variations, however, did not implicate the essence of the Hautmann
      technique. Follow-up of the patients did not reveal high frequency of occurrence
      of any complications.

PMID- 10935140
TI  - Eosinophilic cystitis.
AB  - Authors report on two rare cases of eosinophilic cystitis, giving a review of the
      etiologic assumptions and pathogenetic, pathologic aspects of the disease, based
      on the available literary data. The course of the disease can be either acute or
      subacute, and is most often chronic. Relapse and progression can interchange in
      irregular manner, attention is therefore called to the importance of follow-ups.
      Resection deep into the intact--also containing muscle fibre--as well as
      histologic examination are considered essential as the only method of
      differentiation, giving precise diagnosis in the present two cases, too.

PMID- 10935141
TI  - Comparison of morbidity of lumbar flank approach and transperitoneal approach for
      radical nephrectomy.
AB  - PURPOSE: This is a retrospective study comparing the clinical data and morbidity
      of transperitoneal radical nephrectomy (TRN) and simple nephrectomy. MATERIAL AND
      METHODS: From 1st January, 1989 to 1st January, 1996 a total of 90 simple
      nephrectomies and from 1st January, 1996 to 1st August, 1999 a number of 85 TRN
      were performed at the Department of Urology of the Saint Stephen Hospital. The
      analysis of clinical data included operative time, length of analgesics,
      postoperative hospital stay and blood loss, as well as morbidity. RESULTS: The
      mean operative time for TRN was 170 min., being 95 min. for simple nephrectomy.
      The mean blood loss for TRN was 250 ml, and 400 ml for simple nephrectomy. There
      were different types of morbidity for TRN and simple nephrectomy. The
      complications of TRN mean minimal risk and easy correctibility. CONCLUSION: Our
      results demonstrate an overall clear advantage of TRN when compared to simple
      nephrectomy.

PMID- 10935142
TI  - Metabolic consequences of orthotopic ileal neobladder.
AB  - PURPOSE: Orthotopic ileal bladder substitution is a well accepted form of urinary
      diversion providing high quality of life. However, potential metabolic
      consequences remain a serious problem. These complications are discussed in the
      present article. MATERIAL AND METHODS: Authors review the metabolic complications
      of 45 orthotopic ileal neobladder cases. RESULTS: Insufficient absorption
      (malabsorption) associated with ileal resection is quite rare, while
      hyperchloremic metabolic acidosis after ileal neobladder is a rather common
      phenomenon (55%). CONCLUSION: Authors suggest careful patient selection, correct
      operative technique and vigilant follow-up for successful treatment of metabolic
      complications.

PMID- 10935143
TI  - Isolated urethral amyloidosis (case report).
AB  - A case of urethral amyloidosis is presented in a 31-year-old male patient.
      Through this case, authors draw attention to the recommended forms of examination
      in the event of this illness being suspected, and also discuss problems in
      differential diagnosis. A reviewed the relevant data in the literature is also
      provided.

PMID- 10935144
TI  - Heteromorphic grade of renal cell cancer.
AB  - The present study demonstrates by means of histopathologic analysis that most of
      the renal adenocarcinomas are microscopically heterogeneous--named by authors as
      heteromorphic. This heteromorphism means the mixture of different cell types,
      histological patterns and fields of tumor with different nuclear atypia. 300
      surgical specimens of renal cell cancer (RCC) were reclassified retrospectively.
      The histologic classification was as follows: 1. Nuclear atypia (nuclear grading
      according to Skinner); 2. Histological structure (compact, tubular, papillary,
      cystic); 3. Tumor cell types (clear, chromophobe, chromophilic basophilic,
      chromophilic eosinophilic). Homogeneous tumors consist of the three categories of
      this basic classifications. Heteromorphic tumors have combinations the three
      categories: different cell types (clear and granular) and/or histological
      elements (tubulo-papillary) and/or nuclear structure. Heteromorphism of RCC can
      be graded as: G-I: homogeneous structure (three patterns, one-one pattern of the
      three categories; G-II: 3 + 1 patterns.... G-III: 3 + 2 patterns.... G-IV: 3 + 3
      or more patterns of the classification given above. This grading system is
      recommended for the heteromorphism of renal adenocarcinomas.

PMID- 10935145
TI  - Forgotten rubber drain in the abdomen (case report).
AB  - Forgotten rubber drain in the abdomen is a rarely seen situation after the
      abdominal operations. In this article, a case of "forgotten rubber drain in the
      abdomen after a liver hydatid cyst operation" was presented. The clinical
      significance of the case was discussed by surveying all literature.

PMID- 10935146
TI  - Postinfarction left ventricular remodeling: a pathophysiological and therapeutic
      review.
AB  - Over the last 50 years, studies investigating the pathogenesis of left
      ventricular dysfunction have resulted in many potential therapeutic targets being
      identified and novel classes of drugs designed to treat this condition. Despite
      this, the long-term prognosis of patients with clinical heart failure remains
      poor with mortality rates equivalent to many terminal malignancies. This article
      reviews our present understanding of the pathophysiology of post-infarction left
      ventricular dysfunction and provides a rationale for current drug usage, drugs
      undergoing clinical trials and compounds still under pre-clinical development. In
      addition, the complexities involved in deciphering intra-cellular signalling
      pathways mediating ventricular hypertrophy which may form the basis of future
      treatments are also discussed.

PMID- 10935147
TI  - Effect of glycoprotein IIb/IIIa inhibitors on the individual components of
      composite endpoints used in clinical trials of unstable angina and non-Q-wave
      myocardial infarction.
AB  - Inhibitors of the platelet glycoprotein (GP) IIb/IIIa receptor complex have
      recently been approved for the treatment of patients with unstable angina and non
      Q-wave myocardial infarction (MI). We performed a meta-analysis to ascertain the
      effect of these agents on the individual endpoints of death, myocardial
      infarction, refractory ischemia, and major bleeding after 30 days of follow-up.
      Five randomized, placebo-controlled trials involving 17,255 patients were
      identified. The odds ratios for each of the endpoints in each trial were
      calculated and combined using a fixed-effects model. There was no significant
      reduction in death (OR, 0.87; 95% CI, 0.73-1.03; P = 0.1), myocardial infarction
      (OR, 0.91; 95% CI, 0.82-1.004; P = 0.06), or refractory ischemia (OR, 0.92; 95%
      CI, 0.78-1.1; P = 0.36) in patients treated with GP IIb/IIIa inhibitors. There
      was a significant increase in major bleeding following treatment with GP IIb/IIIa
      inhibitors (OR, 1.2; 95% CI, 1.06-1.4; P = 0.005). When used to treat unstable
      angina and non-Q-wave MI, this new class of agents appears to be associated with
      minimal clinical benefit and an increase in major bleeding complications.

PMID- 10935148
TI  - Comparison of fentanyl and droperidol mixture (neuroleptanalgesia II) with
      morphine on clinical outcomes in unstable angina patients.
AB  - The objective of the study was to compare the influence of a fentanyl and
      droperidol mixture (neuroleptanalgesia) with morphine on the in-hospital
      instability, development of acute myocardial infarction (AMI), and mortality
      during a 30-day and 12-month follow-up in unstable angina patients. The study was
      performed in 112 unstable angina patients. In addition to standard therapy for
      unstable angina (aspirin, heparin, nitroglycerin, and oxygen), 53 patients (63.2
      +/- 9.7 years; 32 males) were randomized to receive neuroleptanalgesia (0.025 mg
      fentanyl and 1.25 mg droperidol in a volume of 1 mL) and 59 patients (58.6 +/-
      11.5 years; 41 males) to receive morphine. Neuroleptanalgesia was started i.v.
      with 2 mL and could be followed by 1 mL every 4 hours. Morphine was started i.v.
      with 10 mg and could be followed by 5 mg every 4 hours up to angina resolution
      during 24 hours of hospitalization. Another 1 mL of neuroleptanalgesia or 5 mg of
      morphine could be administered on demand if angina lasted or reappeared earlier
      than the next scheduled dose. Odds ratios with 95% confidence intervals (95% CI)
      adjusted for the age, sex, smoking, previous myocardial infarction, and
      hypertension were evaluated for all study outcomes. The odds ratios for clinical
      in-hospital instability (5.93, 95% CI: 2.49-14.15; P = 0.0001), 12-month AMI
      development (3.57, 95% CI: 1.51-8.45; P = 0.0038), and 12-month mortality (6.00,
      95% CI: 1.63-22.09; P = 0.0070) were significantly increased in the
      neuroleptanalgesia group compared with the patients on morphine. It is concluded
      that neuroleptanalgesia negatively influences disease course, AMI development,
      and total mortality in unstable angina patients.

PMID- 10935149
TI  - Effect of a calcium-sensitizing agent, levosimendan, on the postcardioplegic
      inotropic response of the myocardium.
AB  - Myocardial contractile function after coronary artery bypass graft surgery is
      often depressed and may require inotropic support, particularly in patients on
      treatment with beta-adrenergic and Ca2+ blockers. In view of the increase in
      cytosolic Ca2+ during early reperfusion, use of Ca2+ sensitizing agents may be
      preferable to adrenergic agonists for enhancement of contractile function after
      cardioplegic arrest. The aim of this study was to assess the efficacy of the Ca2+
      sensitizer, levosimendan, as an inotrope on the mechanical recovery of hearts
      after normothermic and hypothermic cardioplegic arrest in the absence and
      presence of Ca2+ and beta-blockers. Isolated perfused working guinea pig hearts
      were perfused in the absence or presence of propranolol (10(-6) M) and/or
      nifedipine (10(-8) M), subjected to 45 minutes of normothermic or 180 minutes of
      hypothermic cardioplegic arrest, reperfused, and exposed to increasing
      concentrations of levosimendan (10(-9) to 10(-6) M). Levosimendan (10(-7) to 10(
      6) M) has positive inotropic, chronotropic, and vasodilatory effects on normoxic
      perfused control hearts, as well as during reperfusion after 45 minutes of
      normothermic cardioplegic arrest. Similar effects were elicited in the presence
      of the blockers. Levosimendan had no stimulatory effect during reperfusion of
      hearts subjected to prior hypothermic arrest. Except for the increase in heart
      rate, the effects of levosimendan on functional performance during reperfusion
      were comparable with those of adrenaline. Levosimendan elicits a positive
      inotropic and chronotropic response during reperfusion of hearts after
      normothermic cardioplegic arrest, both in the absence and presence of Ca2+ and
      beta-adrenergic blockers.

PMID- 10935151
TI  - Therapeutic approaches to achieve desired blood pressure goals: focus on calcium
      channel blockers.
AB  - The new guidelines for blood pressure control recommended by the World Health
      Organisation, the International Society of Hypertension, and the JNC VI require
      that blood pressure be lowered to levels of < 130/85 mmHg in persons with either
      diabetes or renal insufficiency. A review of over 20 clinical trials performed
      over the last two decades indicates that an average of 62% of the participants
      required more than two medications to achieve a goal of < 140/90 mmHg. Thus, with
      the new guidelines it is clear that an even higher proportion of people will
      require at least two different medications to achieve this lower goal. Certain
      classes of antihypertensive medications are relatively more efficacious for
      lowering blood pressure in certain ethnic and racial groups, thus reducing the
      probability that two or more agents will be needed to achieve a stated blood
      pressure goal. This is exemplified by the effects of calcium channel blockers in
      African-Americans. However, even in these groups many require at least two
      different antihypertensive agents to achieve the blood pressure goal. The fixed
      dose combinations of a calcium channel blocker and ACE inhibitor offer the
      advantages of complementary physiologic action, improved tolerability, lower side
      effect profile, enhanced salutary effects on target organs, better compliance,
      and lower cost. Varieties of fixed-dose combination regimens for blood pressure
      lowering are available for clinical use. This article focuses on the subclasses
      of calcium channel blockers and their role in altering the natural history of
      both cardiovascular and renal disease. The article further discusses the role of
      fixed-dose agents with regard to their place in the antihypertensive
      armamentarium.

PMID- 10935150
TI  - Attenuation of KATP channel-opener induced shortening of repolarization time by
      alpha 1-adrenoceptor antagonist during ischemia in canine heart.
AB  - The purpose of the study was to determine whether a new KATP channel opener, Y
      26763 (Y), can influence the electrophysiological properties in the ischemic
      myocardium as well as to determine whether the blunting effect of the alpha 1
      adrenoceptor antagonist bunazosin (BN) on an ischemia-induced shortening of
      repolarization time can be related to the KATP channel activity. The anterior
      descending branch of the left coronary artery was ligated four times for 5
      minutes, separated by 15 minutes of reperfusion (stages 1-4) to test the dose
      dependent effect of drugs on repolarization. Dogs received either vehicle (n =
      9), Y (0.4, 2.0, and 4.0 micrograms/kg at stages 2, 3, and 4, respectively, with
      0.4 microgram/kg/min drip infusion at each of stages 2-4, n = 7), BN (0.1 mg at
      each of stages 2-4, n = 8), or a combination of these two drugs (BN + Y, the same
      dose of BN and Y in groups BN and Y, respectively, n = 9). Drugs were
      administered into the left atrium. The monophasic action potential (MAP) and
      regional electrograms were recorded. The MAP90 and the duration of the slow
      deflections (DSD) of the regional electrogram were used as markers of
      repolarization. The Vmax of the MAP and the rapid deflections (DRD) of the
      regional electrogram were used as markers of conduction. Y augmented an ischemia
      induced shortening of MAP90 and DSD in proportion to an increase in the dose
      given and the plasma concentration (P < .05-.01), especially at the epicardial
      site. BN and BN + Y blunted the ischemia-related shortening of MAP90 and DSD,
      causing a reduction in repolarization time dispersion between the ischemic and
      normal zones. There were no significant changes in the Vmax or DRD in the
      ischemic zone between periods before and after an increase in each drug dose in
      the four groups. None of the seven dogs developed ventricular tachycardia
      (VT)/ventricular fibrillation (VF) in the Y group, whereas two of the eight dogs
      in the BN group, three of the nine dogs in the BN + Y group, and three of the
      nine dogs in the control group developed VT/VF. These results suggest that the
      alpha 1-adrenergic blocker bunazosin blunts the shortening effect of KATP channel
      activator on repolarization time, and that the KATP channel opener Y may be
      antiarrhythmic, although the repolarization time dispersion during myocardial
      ischemia is increased.

PMID- 10935152
TI  - Long-term cardiovascular effects of high "osteoprotective" dose levels of 17 beta
      estradiol in spontaneously hypertensive rats.
AB  - The effects of estrogen replacement therapy in menopausal women are more obvious
      on bones than on the cardiovascular system. The optimal estrogen dosage may
      differ in these different parts of the body. In hypertensive rats, low doses have
      been shown to reduce arterial collagen and stiffness, whereas higher dosages are
      required for osteoprotection. From 4 to 20 weeks of age, female spontaneously
      hypertensive rats (SHRs) were divided into four groups: without ovariectomy,
      under placebo or 17 beta-estradiol (10 micrograms/kg/day), and with ovariectomy
      under either placebo or 17 beta-estradiol (same dosage). Serial tail systolic
      blood pressure measurements were performed, and histomorphometry of the thoracic
      aorta was determined at the end of the study. Under estrogen, blood pressure was
      unchanged, whereas the aortic wall-to-lumen ratio was increased, particularly in
      the presence of ovariectomy. The elastin to collagen ratio was significantly
      decreased, due both to a decrease in elastin and an increase in collagen density,
      with no change in media thickness. The latter findings were not observed when
      ovariectomy was performed. Independent of changes in wall stress, high-dose
      estrogen increases the aortic extracellular matrix in female SHRs. This increase
      may be reversed in the presence of ovariectomy, suggesting that estrogen was not
      the only gonadal factor responsible for altered vascular structure and function.

PMID- 10935153
TI  - Endothelial dysfunction in hypercholesterolemia is reversed by a nutritional
      product designed to enhance nitric oxide activity.
AB  - The objective of this study was to investigate the vascular and biochemical
      effects of a formulated product in the form of a bar enriched with a combination
      of nutrients known to enhance the synthesis or activity of endothelium-derived
      nitric oxide (EDNO). Individuals with hypercholesterolemia manifest impaired flow
      mediated vasodilation, which is largely due to a reduction in EDNO activity. Oral
      supplementation with large amounts (6-21 g/day) of L-arginine, the precursor of
      EDNO, have been shown to improve endothelium-mediated vasodilation in
      hypercholesterolemia. Such large doses are effective but may be impractical to
      take in capsule form. Accordingly, we have developed a nutrient bar enriched with
      L-arginine as well as other ingredients that additively enhance EDNO activity. A
      pilot study in 41 hypercholesterolemic individuals indicated that the bar was
      well tolerated, had no adverse effects on serum chemistries or lipid profile, and
      normalized endothelial vasodilator function. To definitively determine if the
      nutrient bar normalizes endothelial function, a double-blind, placebo-controlled
      study was performed. Flow-mediated endothelium-dependent vasodilation was
      assessed by high-resolution ultrasonography before and after 1 week of bar use (2
      bars/day) in an additional group of 43 volunteer subjects (57 +/- 10 years old;
      22 men, 21 women) with hypercholesterolemia. Subjects manifested an impaired flow
      mediated vasodilation before the intervention. Vasodilator function in the active
      bar group improved to within a normal range (6.5 +/- 3% before to 10 +/- 5%
      after, P = 0.02; normal, 12 +/- 3%) and was significantly better (P < 0.01) than
      in the placebo bar group (7.1 +/- 3% before to 6.7 +/- 4% after). These findings
      reveal that use of a nutrient bar designed to enhance EDNO activity improves flow
      mediated endothelium-dependent vasodilation in hypercholesterolemic individuals.

PMID- 10935154
TI  - Blockade of angiotensin signaling improves myocardial function in
      hypercholesterolemia independent of changes in eicosanoid release.
AB  - In hypercholesterolemia in the presence or absence of atherosclerosis,
      cardiovascular dysfunction and altered signaling of angiotensin, nitric oxide, or
      prostanoids are closely related to enhanced oxidant stress. We analyzed the
      potentially beneficial effects of the specific angiotensin-converting enzyme
      inhibitor enalapril and the specific angiotensin receptor blocker losartan on
      cardiac performance, eicosanoid metabolism, and parameters of oxidant stress in
      hypercholesterolemic animals. Guinea pigs were fed a 1% cholesterol diet for 8
      weeks (Chol) with or without equieffective doses of either enalapril (1.5
      mg/kg/d; Ena) or losartan (3 mg/kg/d; Los). Hemodynamics were analyzed in
      Langendorff hearts. Detection of eicosanoids was by enzyme immunoassay.
      Estimation of plasma xanthine oxidase (XO) activity was determined by
      spectrophotometry. In hypercholesterolemic guinea pigs, enhanced oxidant stress
      (e.g., increased plasma XO activities) was associated with profound myocardial
      and coronary (e.g., endothelial) dysfunction. Both enalapril and losartan lowered
      plasma cholesterol levels slightly, but only the angiotensin receptor antagonist
      effectively suppressed the increased plasma XO activities (from 11.4 +/- 0.7 to
      7.6 +/- 2.2 U/L), and at the same time decreased the augmented coronary flow
      (from 26.0 +/- 1.0 to 23.0 +/- 1.0 mL/min/g tissue) observed in
      hypercholesterolemic animals. Assessment of left ventricular pressure and
      contractility (e.g., dp/dtmax) as well as the diastolic relaxation parameter
      (tau) revealed substantial myocardial dysfunction (systolic and diastolic) in
      Chol that was more substantially (and comparably) improved during administration
      of losartan (Los) than during enalapril (Ena). Surprisingly, angiotensin
      signaling blockade by either antagonist further suppressed the diminished
      coronary dilator responses to bradykinin (BK; not significant for enalapril) or
      adenosine (Ado) was demonstrated in Chol Langendorff hearts [delta CPPBK/Ado:
      from 5.0 +/- 0.5/0.9 +/- 0.1 to 4.4 +/- 1.5/0.4 +/- 0.1 (Ena) or to 1.9 +/-
      0.5/0.4 +/- 0.1 (Los) cm2 (area under the curve), respectively]. Finally, as
      expected from control studies using heart preparations from normocholesterolemic
      guinea pigs, enhanced cardiac release of eicosanoids, prostacyclin, and
      thromboxane in Chol (0.48 +/- 0.03 and 0.6 +/- 0.1 ng/min/g) was augmented even
      further by treatment with enalapril (Ena: 1.6 +/- 0.4 and 1.0 +/- 0.1 ng/min/g),
      but was significantly reduced to or below control levels in losartan-treated
      animals (Los: 0.4 +/- 0.1 and 0.2 +/- 0.1 ng/min/g). Blockade of angiotensin
      signaling via angiotensin-converting enzyme inhibition or receptor antagonism-
      although differentially acting on enhanced cardiac prostanoid metabolism and
      oxidant stress--efficiently restored proper systolic and diastolic myocardial
      performance (losartan was more beneficial than enalapril), probably by
      counterbalancing altered angiotensin II-->angiotensin receptor signaling in the
      cardiovascular system of hypercholesterolemic animals. Impaired coronary
      vasodilator capacity seems to be irreversible after 8 weeks of a high-cholesterol
      diet, as shown by the unexpected lack of a dilator effect with both enalapril and
      losartan.

PMID- 10935155
TI  - Chronic treatment with FK506 increases p70 S6 kinase activity associated with
      reduced nitric oxide synthase activity in rabbit hearts.
AB  - FK506, an immunosuppressant, modulates phosphorylation of nitric oxide (NO)
      synthase, and induces cardiac hypertrophy in clinical settings. Having recently
      reported that chronic treatment with an inhibitor of NO synthase induces cardiac
      hypertrophy associated with the activation of 70-kD S6 kinase (p70S6K), which
      plays an important role in cardiac hypertrophy by regulating protein synthesis,
      we investigated the effects of chronic administration of FK506 on NO synthase and
      p70S6K activities in hearts. Twenty rabbits were divided into four groups:
      untreated rabbits, those treated with low-dose FK506 (0.10 mg/kg), those treated
      with medium-dose FK506 (0.20 mg/kg), and those treated with high-dose FK506 (0.40
      mg/kg). FK506 was administered intravenously twice a day. After 4 weeks of
      treatment with FK506, calcium-dependent NO synthase activity in myocardium in the
      high-dose FK506 group was lower (P < 0.05) than in the untreated group. p70S6K
      activity in myocardium in the high-dose group was higher (P < 0.05) than in the
      untreated group. There was a significant (P < 0.05) inverse correlation between
      NO synthase and p70S6K activities in myocardium. However, the endothelial
      dependent vasodilation of aortic rings or plasma levels of NO metabolites during
      experimental protocols did not differ among the groups studied. These findings
      suggest that chronic treatment of FK506 activates p70S6K and reduces NO synthase
      activity in rabbit hearts. Reduced NO synthase and/or activated p70S6K activities
      in hearts might contribute to the cardiac hypertrophy observed in some patients
      receiving FK506.

PMID- 10935156
TI  - SB 203580, a mitogen-activated protein kinase inhibitor, abolishes resistance to
      myocardial infarction induced by heat stress.
AB  - Heat stress (HS) is known to confer protection against ischemia-reperfusion
      injury, including mechanical dysfunction and myocardial necrosis. However, the
      mechanisms involved in this cardioprotection are yet to be elucidated. Mitogen
      activated protein (MAP) kinase cascades have been demonstrated to be involved in
      cellular response to different stresses. In particular, p38 MAP kinase is known
      to be activated by HS. Therefore, we investigated the implication of this kinase
      in HS-induced resistance to myocardial infarction, in the isolated rat heart
      model, using SB 203580 (SB) to selectively inhibit p38 MAP kinase. Rats were
      treated with SB (2.83 mg/kg, i.p.) or vehicle (1% DMSO in saline, i.p.) before
      they were either heat stressed (42 degrees C for 15 minutes) or sham
      anesthetized. Their hearts were isolated 24 hours later, retrogradely perfused,
      and subjected to a 35-minute occlusion of the left coronary artery followed by
      120 minutes of reperfusion. The infarct-to-risk ratio was significantly reduced
      in HS (16.9 +/- 2.0%) compared with sham (41.6 +/- 2.5%) hearts. This reduction
      in infarct size was abolished in the SB 203580-treated group (37.8 +/- 1.9% in HS
      + SB vs. 42.0 +/- 1.9% in sham + SB). Risk zones were similar between
      experimental groups. Western blot analysis of the myocardial HSP72 showed an HS
      induced increase of this protein, which was not modified by the p38 MAP kinase
      inhibitor, SB 203580. We conclude that activation of p38 MAP kinase appears to
      play a role in the functional cardioprotection associated with the heat stress
      response, which seems to be unrelated to the HSP72 level. Further investigations
      are required to elucidate the precise role of the p38 MAP kinase and heat stress
      proteins in this adaptative response.

PMID- 10935157
TI  - Cardiovascular disease in developing countries.

PMID- 10935158
TI  - What about beta-blockers in the new glucose-insulin-potassium (GIK) era?

PMID- 10935159
TI  - Cloning and sequencing of sialyltransferase gene from human fetal liver.
AB  - Based on sequences of the highly conserved segments in the previously cloned
      sialyltransferases, 150 bp fragments were amplified and sequenced using human
      fetal liver mRNA as template. One of them (s38) showed 57%-97% identities with
      the active domains of previously cloned sialyltransferases. Based on the sequence
      of s38, an oligonucleotide was synthesized and labeled to screen human fetal
      liver cDNA library. A cDNA encoding alpha 2, 3-sialyltransferase has been
      isolated. The cDNA sequence included an open reading frame coding for 340 amino
      acid residues, and the deduced amino acid sequence showed 100% identity with that
      of human submaxillary gland Gal beta 1, 3GalNAc alpha 2, 3-sialyltransferase,
      83.2% identity with that of pig submaxillary gland alpha 2, 3-sialyltransferase.
      These results suggested that the protein encoded by the cDNA from human fetal
      liver cDNA library was a Gal beta 1, 3GalNAc alpha 2, 3-sialyltransferase.

PMID- 10935160
TI  - Site-directed mutagenesis analysis of draTG genes and their downstream region
      from Azospirillum brasilense Yu62.
AB  - draT and draG genes are involved in posttranslational regulation of nitrogenase
      activity of Azospirillum brasilense Yu62. Both genes and their downstream region
      were mutagenized by Kmr cassette insertions. Analysis of mutations introduced
      into the draTG region on the A. brasilense Yu62 chromosome showed that mutants
      affected in draT were incapable of regulating nitrogenase activity in response to
      ammonium. In contrast, a mutant with an insertion in draG was still capable of
      ADP-ribosylating dinitrogenase reductase in response to ammonium but was no
      longer able to recover activity after ammonium depletion. Analysis of mutations
      introduced into the draTG downstream region (the mutagenized site is about 2 kb
      downstream from draG) showed that the mutant had higher nitrogenase activity than
      the wild strain while growing in nitrogen-free medium and medium with 2 mmol/L
      ammonium. These results reveal that there is no gene required for nitrogen
      fixation in this mutagenized region, but it is possible that there are genes
      which play a role in regulating nitrogen fixation. The results of monitoring the
      expression of transcriptional nifH-lacZ gene fusion in the mutant YZ4 showed that
      the transcriptional regulation of nif gene in the mutant YZ4 was the same as that
      in the wild type.

PMID- 10935161
TI  - Expression, purification, and bone-inducing activity of recombinant human bone
      morphogenetic protein-3 mature peptide.
AB  - It was inferred that the mature peptide of human bone morphogenetic protein-3
      (hBMP-3m) consists of the carboxyl terminal 127 amino acid residues of hBMP-3. A
      plasmid, pDH-B3m, was constructed by inserting the cDNA sequences encoding hBMP
      3m into pDH, a PL-containing expression vector. pDH-B3m was transformed into
      Escherichia coli DH5 alpha. The highest expression level of recombinant hBMP-3m
      (rhBMP-3m) could be reached after 6 hours of induction at 42 degrees C,
      accounting for 28% of the total bacterial proteins. The rhBMP-3m was found in the
      inclusion bodies. After being washed and partially purified, the inclusion bodies
      were solubilized in urea and purified efficiently through ion-exchange
      chromatography. The purity of the rhBMP-3m was at least 95%. The rhBMP-3m was
      refolded by dilution method and then 1 mg was implanted into mouse thigh muscle
      to assay its activity. A classic pattern of cartilaginous osteogenesis was
      observed. The results showed that the purified and refolded rhBMP-3m had ectopic
      bone-inducing activity.

PMID- 10935162
TI  - Expression of nerve growth factor from Agkistrodon halys Pallas in E. coli and
      its purification.
AB  - The nerve growth factor (NGF) gene of Agkistrodon halys Pallas was cloned into a
      secretive prokaryotic expression vector pET-22b+ which carried a C-terminal His.
      Tag sequence. After transforming into E. coli BL21 (DE3), NGF was induced to
      express at 30 degrees C by IPTG. SDS-PAGE analysis showed an induced expression
      product band which constituted about 20% of the total bacterial proteins.
      However, its molecular weight was larger than what was expected. Moreover, the
      analysis of product solubility revealed that NGF was in the form of inclusion
      bodies. The inclusion bodies were solubilized in 6 mumol/L guanidine HCl and
      purified directly by immobilized metal (Ni2+) chelation affinity chromatography.
      The product was renatured by dilution and air oxidation in the presence of 5
      mumol/L CuSO4, and was proved active by examining the survival rate of PC12 cells
      in a serum-free medium.

PMID- 10935163
TI  - Cultivation of encapsulated yeast cells in NaCS-PDMDAAC polyelectrolyte
      complexes.
AB  - The cultivation of encapsulated S. cerevisiate and C. utilis in NaCS-PDMDAAC
      Polyelectrolyte Complexes was studied. The results showed that these two kinds of
      encapsulated microorganisms showed the same growing properties as in their free
      cell cultures, and thus NaCS-PDMDAAC microcapsules were suitable for the
      encapsulation of biological substances. The encapsulated S. cerevisiate cells
      were fermented sequentially for 16 batches. The highest cell density in the
      capsules reached 2.64 x 10(10) cells/mL and ethanol concentration reached 47.0
      g/L. The encapsulated C. utilis produced the same amount of GSH as the free cell
      culture.

PMID- 10935164
TI  - Factors influencing the synthesis of monoester and diester from polyethylene
      glycol400 and oleic acid by lipase.
AB  - Factors influencing the synthesis of mono- and diester of polyethylene glycol400
      (PEG400) oleate with immobilized lipase from Candida sp.1619 as biocatalyst were
      investigated. Mono- and diester were formed with different molar ratios of the
      substrates after reacting for 6 hours. The amount of monoester to diester formed
      was in the range of 3.5:1 to 4.1:1 when the molar ratio of acid to PEG400 was
      0.25:1 to 2:1. Almost equal amounts of mono- and diesters were produced when the
      molar ratio of acid to PEG400 was 3:1 to 8:1. When the equilibrium of reaction
      was reached (22 hours), only diester was found in the reaction mixture with
      different molar ratio of substrates. The amount of monoester to diester was 1:3.2
      in the reaction system containing hexane, even the molar ratio of acid to PEG400
      was 2:1.

PMID- 10935165
TI  - A new system for expressing heterologous gene in Escherichia coli regulated by
      oxygen consistence in the environment.
AB  - The expression of Vitreosilla hemoglobin gene (vgb) is regulated by oxygen
      consistence in E. coli. The gene transcription is activated under the condition
      of limited oxygen. A new system for expressing heterologous gene in E. coli
      regulated by dissolved oxygen consistence was constructed. It includes a host
      bacteria GJ100, which contained T7 RNA polymerase gene controlled by vgb
      promoter, and an expression vector on which the heterologous gene was under the
      control of a T7 promoter. The results indicated that E. coli thioredoxin A, IgG
      binding domain of Staphylococcus protein A(ZZ), snake neurotoxin, salmon
      calcitonin hexa-polymer, human interleukinII (IL2) and human pro-urokinase genes
      could be expressed efficiently. Expression level was more than 30% of the total
      cellular protein.

PMID- 10935166
TI  - Studies on biosensor to determine diacetyl.
AB  - We studied the purification of diacetyl reductase, the preparation of a
      biosensor, and its performance. With diacetyl reductase and reduced coenzyme I
      (NADH) co-immobilized as working membrane, NAD+/NADH produced in the course of
      diacetyl reduction was connected with Fe2+/Fe to build a biosensor. The biosensor
      could be used to determine diacetyl concentration within the range from 0.1
      microgram/mL to 0.5 microgram/mL and the response time was less than two minutes,
      and its performance was stable within 9 days. The experiments showed that typical
      metal ions and organics in nominal concentration did not affect the performance
      of the biosensor, meanwhile, the interference of dissolved oxygen on the
      performance of biosensor and regeneration of coenzyme I (NADH) were solved to
      some extent.

PMID- 10935167
TI  - Influence of FL on ex vivo expansion of hematopoietic cells from cord blood in
      long-term liquid cultures.
AB  - The use of umbilical cord blood for stem cell transplantation has numerous
      advantages, but a major deficiency is the rather low cell number available.
      Therefore, ex vivo expansion were proposed to overcome this limitation. In this
      paper the effects of flt-3 ligand (FL), stem cell factor (SCF), interleukin(IL)
      3, IL-6, granulocyte colony-stimulating factor (G-CSF) and granulocyte- monocyte
      colony-stimulating factor (GM-CSF) on long-term ex vivo expansion and
      differentiation of cord blood hematopoietic cells were investigated. In the
      culture containing FL + SCF + G-CSF + GM-CSF, the total cell expansion ratio
      reached the maximum (385.30 +/- 163.51-fold) at 28 days, whereas in the culture
      with FL + SCF + IL-3 + IL-6, CFU-GMs expansion ratio reached a plateau (409.52 +/
      189.50-fold) at 28 days. FL synergized with SCF and other cytokines. In all the
      conditions investigated, cultures with FL obtained an increase of fold expansion
      in both total cells and CFU-GMs. The combination of FL + SCF does not benefit the
      proliferation of the total cells, however, the expansion of CFU-GM was kept at a
      high level. Apparently, both cytokines maintained the activities of
      stem/progenitor cells and hampered differentiation. In the presence of G-CSF and
      GM-CSF, total cells enhanced quickly, and had the most expansion of total cells
      in comparison with other combinations. However, CFU-GM output peaked at 18 days
      and subsequently dropped to 0 promptly, suggesting that G-CSF and GM-CSF inspired
      differentiation.

PMID- 10935168
TI  - The role of genotype in activation and priming of the respiratory burst in
      neutrophils.

PMID- 10935169
TI  - Nitrogen oxide is an endogenous source of coupled oxidation and methylation of
      animal DNA.

PMID- 10935170
TI  - Aminoxidase from the archebacterium Methanosarcina barkeri.

PMID- 10935171
TI  - Effects of synthetic peptides TQVEHR and TGENHR on early mouse embryo development
      in vitro.

PMID- 10935172
TI  - Nonrandom distribution of the endogenous retroviral regulatory elements HERV-K
      LTR on human chromosome 22.

PMID- 10935173
TI  - Adaptogenic effect of furostanol glycosides on photosynthetic pigments of tomato
      leaves under stress.

PMID- 10935174
TI  - Effect of alteration in the BGL2 gene on structural changes in the cell wall of
      yeast Saccharomyces cerevisiae.

PMID- 10935175
TI  - The effect of substrate structure on the mechanism of reversible inhibition of
      cholinesterases.

PMID- 10935176
TI  - On the relationship between the anabolic and catabolic phases of the terminal
      protein metabolism in Black Sea mussel fry.

PMID- 10935177
TI  - Molecular cloning of a new mouse gene tagL containing a lysozyme-like domain.

PMID- 10935178
TI  - Replicative protein A exhibits a specific polarity in binding single-stranded
      DNA.

PMID- 10935179
TI  - 5-Methylcytosine in mitochondrial DNA of Pisum sativum L.

PMID- 10935180
TI  - Mutant human gamma-interferon with a truncated C-terminus and its properties.

PMID- 10935181
TI  - Detection of neurotransmitter amines in microorganisms with the use of high
      performance liquid chromatography.

PMID- 10935182
TI  - Stigma and societal response to leprosy: experience of the last half century.

PMID- 10935183
TI  - Search for newer antileprosy drugs.
AB  - In 1991 World Health Organization proclaimed the goal of global elimination of
      leprosy as a public health problem by year 2000 by implementing multidrug therapy
      (MDT). Since then the prevalence rate has declined by 85%. However, during the
      same period the incidence rate of leprosy has remained constant or even has been
      increasing. This suggests that it will take a long time for the eradication of
      leprosy and that without in-vitro cultivation of M. leprae, eradication of
      leprosy is not likely to be achieved. While in-vitro cultivation is a long-term
      goal, as an immediate measure, there is an urgent need for the development of
      newer drugs and newer multidrug therapy regimens. Using the in-vitro system for
      screening potential antileprosy drugs and also using the mouse foot-pad system we
      have evaluated several compounds in four classes of drugs--dihydrofolate
      reductase inhibitors, fluoroquinolones, rifampicin analogues and phenazines--and
      identified at least two compounds that appear to be more potent than dapsone,
      rifampicin and clofazimine. Newer combinations of rifampicin analogues and
      fluoroquinolones have also been identified that seem to be better than the
      combination of rifampicin and ofloxacin.

PMID- 10935184
TI  - Immunotherapy and immunoprophylaxis of leprosy.

PMID- 10935185
TI  - Remaining challenges towards the elimination of leprosy. Leprosy Elimination
      Project World Health Organization.

PMID- 10935186
TI  - Detecting peripheral nerve damage in the field: our tools in 2000 and beyond.

PMID- 10935187
TI  - Leprosy control, elimination and eradication.

PMID- 10935188
TI  - Mechanics of tarsal disintegration and plantar ulcers in leprosy by stress
      analysis in three dimensional foot models.
AB  - This paper describes three dimensional two arch models of feet of a normal
      subject and two leprosy subjects, one in the early stage and the other in the
      advanced stage of tarsal disintegration, used for analysis of skeletal and
      plantar soft tissue stresses by finite element technique using NISA software
      package. The model considered the foot geometry (obtained from X-rays), foot
      bone, cartilages, ligaments, important muscle forces and sole soft tissue. The
      stress analysis is carried out for the foot models simulating quasi-static
      walking phases of heel-strike, mid-stance and push-off. The analysis of the
      normal foot model shows that highest stresses occur at push-off over the dorsal
      central part of lateral and medial metatarsals and dorsal junction of calcaneus
      and cuboid and neck of talus. The skeletal stresses, in early state leprosy with
      muscle paralysis and in the advanced stage of tarsal distintegration (TD), are
      higher than those for the normal foot model, by 24% to 65% and 30% to 400%,
      respectively. The vertical stresses in the soft tissue at the foot-ground
      interface match well with experimentally measured foot pressures and for the
      normal and leprosy subjects they are the highest in the push-off phase. In the
      leprosy subject with advanced TD, the highest soft tissue stresses and shear
      stresses (about three times the normal value) occur in push-off phase in the scar
      tissue region. The difference in shear stresses between the sole and the adjacent
      soft tissue layer in the scar tissue for the same subject is about three times
      the normal value. It is concluded that the high bone stresses in leprosy may be
      responsible for tarsal distintegration when the bone mechanical strength
      decreases due to osteoporosis and the combined effect of high value of footsole
      vertical stresses, shear stresses and the relative shear stresses between two
      adjacent soft tissue layers may be responsible for plantar ulcers in the
      neuropathic leprosy feet.

PMID- 10935189
TI  - Elimination of leprosy: aspirations, achievements and prospects.

PMID- 10935190
TI  - Current views on reactions in leprosy.

PMID- 10935191
TI  - Systemic involvement in leprosy and its significance.

PMID- 10935192
TI  - Developments in experimental leprosy.

PMID- 10935194
TI  - Microwave heating in the hydrogen peroxide oxidation of benzene on zeolite
      catalysts
AB  - In this paper benzene hydroxylation with hydrogen peroxide (H2O2) in the presence
      of the titan-silicates-zeolites was studied. The initial catalyst, HZSM-5 zeolite
      type was treated to obtain both cobalt- and titan-silicates--zeolite. These
      improved catalysts were also used for oxidation. To obtain reaction temperature
      heating was made by conventional techniques and by microwave treatment. From this
      research it was concluded that reaction temperature is a very important parameter
      to keep a proper equilibrium between the decomposition rate of hydrogen peroxide
      and the oxidation rate of aromatic compound. It was also found that microwaves
      affect the reaction selectivity.

PMID- 10935195
TI  - Pressure-aided microwave rubber vulcanization in a ridged three-zone cylindrical
      cavity
AB  - The characteristics of pressure-assisted microwave vulcanization of rubber were
      studied in a monomode cavity. For this purpose a modified cylindrical cavity was
      designed taking into account the external pressure of dielectric molds at the
      same time that heating was taking place. The monitoring of dielectric properties
      of rubber sample during the vulcanization process was demonstrated to be of the
      utmost importance to correlate the evolution of the rubber when is heated with
      microwaves with the main processing parameters (viscosity and degree of cure).
      The results obtained looked promising as the vulcanization rates were accelerated
      giving vulcanized samples comparable in quality to conventional treatment
      methods.

PMID- 10935193
TI  - Coupled electromagnetic and thermal modeling of microwave oven heating of foods.
AB  - Temperature distributions from heating in a domestic microwave oven were studied
      by considering the coupling between the electromagnetics and heat transfer
      through changes in dielectric properties during heating. Maxwell's equations for
      electromagnetics and the thermal energy equations are solved numerically using
      two separate finite-element softwares. The coupling between the softwares was
      developed by writing special modules that interfaced these softwares at the
      system level. Experimentally measured temperature profiles were compared with the
      numerical predictions. The importance of coupling was evident when the properties
      changed significantly with temperature for low and high dielectric loss materials
      and more so for the high loss materials. For moderate loss materials, when the
      properties do not change as much with temperature, coupled solutions lead to
      results very close to the results for the uncoupled solution.

PMID- 10935196
TI  - Dielectric behavior of SrTiO3 and YiBa2CU3Ox at 10.6 GHz using a microwave
      resonant cavity as a probe
AB  - A cylindrical microwave resonant cavity operating in the TE011 mode was used to
      study the dielectric response of SrTiO3 and YiBa2CU3Ox. The microwave dielectric
      response of the powdered samples of these materials is studied as a function of
      temperature at a frequency of 10.6 GHz. For this study, a very precise heating
      and cooling system was designed to control the temperature accurately to a tenth
      of a degree. The real and imaginary parts of the complex permittivity were
      studied using Slater's Perturbation equations. The relaxation times of these
      materials are derived using Debye's equations for polar molecules.

PMID- 10935197
TI  - Incorporation of the waveguide feed and cavity wall losses into a
      cartesian/cylindrical hybrid finite-difference time domain analysis of a
      geometrically-composite microwave applicator
AB  - A Surface-Impedance Boundary Condition (SIBC) formulation is combined for the
      first time with a Cartesian/cylindrical hybrid Finite-Difference Time Domain (FD
      TD) algorithm to investigate the effects on the electromagnetic characterization
      of a geometrically-composite microwave heating applicator introduced by the
      finite conductivity of the waveguide feed and cavity walls. The computational
      accuracy of the proposed scheme is validated in terms of the energy balance
      principle. Computer simulations revealed that the inclusion of wall losses has
      negligible effects on the interior field distribution and the reflection
      coefficient, S11. Finally, the formulation developed in this paper can be
      employed in estimating the wall losses of other microwave-applicator systems with
      similar surface characteristics.

PMID- 10935198
TI  - Reduction of multiple reflection influence in microwave free-space measurements
AB  - The influence of the multiple reflections is one of the main error sources in the
      microwave free-space measurements. In this study, the influence is analyzed for
      the conventional free-space method, and a new method which uses absorbing
      material inserted between the antenna and the sample to reduce the influence of
      the multiple reflections is proposed. The effectiveness of this approach is
      verified by measuring the attenuation of timbers. It is showed that the maximum
      error caused by the multiple reflections in the improved free-space set-up is 0.4
      dB, while that in the conventional free-space method is 1.5 dB.

PMID- 10935199
TI  - Numerical modeling of the temperature distribution within a bonded paper web when
      undergoing microwave heating in a waveguide
AB  - In this paper, a numerical technique is used to study the temperature
      distribution within the heated bonded paper web placed in a waveguide. The
      parameters of the problem were selected so as to best locate the test sample that
      would generate the desired absorbed power. The method of false transient was
      utilized to accelerate the numerical convergence and the equations were
      discretized with central difference in both time and space. The resulting system
      of equations was solved using an Alternating Direction Implicit scheme. Good
      agreement was achieved between the numerical solutions and the experimental
      validations.

PMID- 10935200
TI  - An algorithm for predicting proton nuclear magnetic resonance deshielding over a
      carbon-carbon double bond.
AB  - Hydrogen nuclei located over a carbon-carbon double bond in a strong magnetic
      field experience NMR shielding effects that result from the magnetic anisotropy
      of the nearby double bond and various other intramolecular shielding effects. We
      have used GIAO, a subroutine in Gaussian 98, to calculate isotropic shielding
      values and to predict the proton NMR shielding increment for a simple model
      system: methane held in various orientations, positions, and distances over
      ethene. The average proton NMR shielding increments of several orientations of
      methane have been plotted versus the Cartesian coordinates of the methane protons
      relative to the center of ethene. A single empirical equation for predicting the
      NMR shielding experienced by protons over a carbon-carbon double bond has been
      developed from these data. The predictive capability of this equation has been
      validated by comparing the shielding increments for several alkenes calculated
      using our equation to the experimentally observed shielding increments. This
      equation predicts the NMR shielding effects more accurately than previous models
      that were based on fewer geometries of methane over ethene. In fact, deshielding
      is predicted by this equation for protons over the center and within about 3 A of
      a carbon-carbon double bond. This result is in sharp contrast to predictions made
      by the long-held McConnell "shielding cone" model found in nearly every textbook
      on NMR, but is consistent with experimental observations. The algorithm for
      predicting the (de)shielding increment for a proton over an alkene can be used in
      a spreadsheet on a PC or incorporated into software that estimates chemical
      shifts using additive substituent constants or a database of structures. In
      either application its use can substantially improve the accuracy of the
      estimated chemical shift of a proton in the vicinity of a carbon-carbon double
      bond, and thus assist in spectral assignments and in correct structure
      determination.

PMID- 10935201
TI  - Construction of a 3D model of oligopeptidase B, a potential processing enzyme in
      prokaryotes.
AB  - A three dimensional structural model of oligopeptidase B (OpB) was constructed by
      homology modeling. High resolution X-ray structure of prolyl oligopeptidase
      (PEP), the only protein with sequential and functional homology was used as a
      template. Initial models of OpB were built by the MODELLER and were analysed by
      the PROCHECK programs. The best quality model was chosen for further refinement
      by two different techniques--either constrained molecular dynamics simulations or
      simulated annealing calculations starting from 500 K. The overall quality of each
      of the refined models was evaluated and the simulated annealing procedure found
      to be more effective. The refined model was analysed by different protein
      analysis programs including PROCHECK for the evaluation of the Ramachandran plot
      quality, PROSA for testing interaction energies and WHATIF for the calculation of
      packing quality. This structure was found to be satisfactory and also stable at
      room temperature as demonstrated by a 300 ps long unconstrained molecular
      dynamics simulation. Calculation of molecular electrostatic potentials revealed
      that the binding site of OpB is more negative than that of PEP, in accordance
      with the experimentally observed selectivity of OpB towards proteolysis at
      dibasic sites. A recently developed Monte Carlo docking method was used provide a
      structural rationale for the affinity differences measured between Z-Arg and Z
      Arg-Arg substrates.

PMID- 10935202
TI  - Connective eccentricity index: a novel topological descriptor for predicting
      biological activity.
AB  - A simple, adjacency-cum-path length based, topological descriptor termed the
      connective eccentricity index has been conceptualized and its discriminating
      power investigated with regard to antihypertensive activity. A data set
      consisting of 81 derivatives of N-benzylimidazole was selected for the present
      investigation. These derivatives are potent, competitive, and nonpeptide
      angiotensin II receptor antagonists. The value of connective eccentricity index
      for each derivative was computed and active range identified. Subsequently, each
      derivative was assigned a biological activity that was compared with the reported
      antihypertensive activity. The results obtained using connective eccentricity
      index were better than the corresponding values obtained using Balaban's mean
      square distance index. The accuracy of prediction was found to be about 80% in
      the active range using connective eccentricity index.

PMID- 10935203
TI  - Stereolithographic models of biopolymers.
AB  - Stereolithography (STL) has been used to make plastic models of the solvent
      accessible surfaces of biopolymers. Models have been made of proteins and
      proteins bound to DNA and RNA. The STL process uses a laser to photopolymerize a
      liquid resin. Using the ACES (accurate, clear, epoxy, solid) building technique,
      parts are made with minimum postcure shrinkage. Protein Data Bank files are
      converted to STL files that represent the surface topology of the biopolymer as a
      series of triangles and an index that describes their orientation. The models are
      useful in teaching biomolecular structure and the principle of docking. They are
      especially useful to the visually impaired.

PMID- 10935204
TI  - A cellular automata model of an anticipatory system.
AB  - An anticipatory system has been modeled using the dynamic characteristics of
      cellular automata. Rules governing the steps in an enzymatic conversion of
      substrates to products are operative in the system. A concentration of an
      intermediate product influences the creation of a supplemental enzyme that
      enhances the competence of an enzyme down stream. This anticipation of the future
      event creates a condition in which the concentration of a later substrate is
      suppressed, a property characteristic of the system. The model presents a useful
      opportunity to study a variety of aspects of this fascinating phenomena.

PMID- 10935205
TI  - QSAR and molecular graphics analysis of N2-phenylguanines as inhibitors of herpes
      simplex virus thymidine kinases.
AB  - A quantitative structure-activity relationship study of N2-(substituted)
      phenylguanines (PHG) as inhibitors of herpes simplex virus thymidine kinase (HSV
      TK) was performed. The activity of a set of PHG derivatives were analyzed against
      the thymidine kinase of herpes simplex virus types 1 (HSV1 TK) and 2 (HSV2 TK).
      Classic and calculated physicochemical parameters were included in the analysis.
      The results showed that there is an important difference in the activity of the
      meta substituted PHG derivatives against HSV1 TK and HSV2 TK. The activity of the
      meta derivatives against HSV2 TK is influenced by a steric effect, which is not
      observed against HSV1 TK. The superposition of the three-dimensional structures
      of the active sites of HSV1 TK (crystal structure) and HSV2 TK (homology model)
      revealed that the amino acid Ile97 is located near the meta position in the HSV1
      TK active site, whereas the amino acid Leu97 is located near the meta position in
      the HSV2 TK active site. This single difference in the active sites of both
      enzymes can explain the source of the steric effect and serves as an indication
      that our previously proposed binding mode for the PHG derivatives is plausible.
      However, another observed mutation in the active site region, Ala168 by Ser168,
      suggests that an alternative binding mode, similar to that of ganciclovir, could
      be possible.

PMID- 10935206
TI  - QM/MM and SCRF studies of the ionization state of 8-methylpterin substrate bound
      to dihydrofolate reductase: existence of a low-barrier hydrogen bond.
AB  - Using combined semiempirical quantum mechanics and molecular mechanics (QM/MM)
      and ab initio self-consistent reaction field (SCRF) calculations, we determined
      that a low-barrier hydrogen bond (LBHB) is formed when the mechanism-based
      substrate 8-methylpterin binds to dihydrofolate reductase (DHFR). The substrate
      initially was assumed bound either in the ion-pair form corresponding to N3
      protonated substrate hydrogen (H) bonded to the unprotonated (carboxylate) of the
      conserved Glu30 residue in the active site, or in the neutral-pair form
      corresponding to unprotonated substrate H bonded to the neutral (carboxylic acid)
      from of Glu30. The free energy of interaction of these H-bonded systems with the
      protein/solvent surroundings was computed using a coordinate-coupled free energy
      perturbation (FEP) method implemented within the molecular dynamics (MD)
      simulation scheme and using a semiempirical (PM3) QM/MM force field. The free
      energy obtained from the QM/MM force-field simulations corresponds most closely
      with the corresponding free energy component obtained from HF/6-31G* SCRF
      calculations using a value of 2 for the dielectric constant (epsilon) for the
      solvated protein. Calculations were performed at levels ranging from HF/6-31G to
      MP2/6-31G* to B3LYP/6-31 + G**, with varying dielectric constants. The energy
      minimized path for motion of the proton in the H bond along a one-dimensional
      reaction coordinate was calculated at HF/6-31G, HF/6-31G* (epsilon = 1) and
      B3LYP/6-31G* (epsilon = 2) levels. These calculations identified a second neutral
      pair complex, involving the 2-amino group of substrate, which also interacts with
      Glu30, which is lower in energy than the ion-pair form. A harmonic vibrational
      analysis shows that the first vibrational state appears to lie near or above the
      TS connecting potential energy minima corresponding to the two neutral-pair
      configurations, thus indicating an LBHB. Consequently, the H-bonded system will
      have a significant probability of being found in the ion-pair form, in agreement
      with experimental spectral studies indicating an enzyme-bound cation and
      suggesting that the LBHB would activate substrate towards hydride-ion transfer
      from NADPH.

PMID- 10935208
TI  - Patenting inventions in combinatorial chemistry.
AB  - I have intended to provide an overview of some patent strategies for protecting
      intellectual property in the combinatorial chemistry arts, along with examples
      taken from recently issued patents. The opinions in this paper are those of the
      author, and are not intended to be relied upon as legal advice. Specific
      questions about any particular patent or invention should be discussed with
      competent counsel before action is taken. If you would like to look at the
      patents discussed in this article, they are available on-line at
      http:?www.patents.ibm.com/boolquery and at other locations.

PMID- 10935207
TI  - A combined QM/MM study of the nucleophilic addition reaction of methanethiolate
      and N-methylacetamide.
AB  - A combined quantum mechanical (QM) and molecular mechanical (MM) method was used
      to study the nucleophilic addition reaction of methanethiolate to N
      methylacetamide (NMA) in the gas phase and aqueous solution. At the B3LYP/aug-cc
      pVDZ//HF/6-31 + G(d) level, the ion-dipole complex was found to be the global
      minimum on the potential energy surface in the gas phase with a binding energy of
      21.2 kcal/mol. The complex has a C-S distance of 4.33 A, and no stabilized
      tetrahedral intermediate was located. The computed potential of mean force in
      water shows that solvent effects stabilize the reactants over the tetrahedral
      adduct by 36.5 kcal/mol, and that the tetrahedral intermediate does not exist for
      the present reaction in water. The present study provides an initial step for
      modeling the cysteine protease hydrolysis reactions in enzymes.

PMID- 10935209
TI  - The art of molecular graphics. Escape from flatland.

PMID- 10935210
TI  - Shannon entropy--a novel concept in molecular descriptor and diversity analysis.

PMID- 10935211
TI  - LeadScope: data visualization for large volumes of chemical and biological
      screening data.

PMID- 10935212
TI  - Decision analytics software solutions for proteomics analysis.

PMID- 10935213
TI  - Diagnostic utility of CSF soluble CD27 for primary central nervous system
      lymphoma in immunocompetent patients.
AB  - The aim of this study is to determine the diagnostic utility of cerebrospinal
      fluid (CSF) soluble CD27 (sCD27) as a tumor marker for primary central nervous
      system lymphoma (PCNSL) in immunocompetent patients. A total of 93 CSF samples
      were collected from the following four patient groups: the PCNSL group, 13
      patients (26 samples) with PCNSL, 12 samples obtained at initial diagnosis, 10
      during therapy, four at complete remission; the other brain tumors (OBT) group,
      30 patients (30 samples) with other brain tumors; the other neurological diseases
      (OND) group, 25 (25 samples) with other neurological diseases; the inflammatory
      neurological diseases (IND) group, 12 patients (12 samples) with inflammatory
      neurological diseases. sCD27 levels were determined by sandwich enzyme-linked
      immunosorbent assay. The optimal cut-off value was found to be 15 U ml-1. The CSF
      sCD27 levels were over 15 U ml-1 in 23 of the 26 PCNSL samples and were
      significantly higher than those in the OBT and OND groups in which all samples
      were below 15 U ml-1. Elevated CSF sCD27 levels were also observed in 11 of 12
      IND samples. In the two PCNSL patients whose CSF sCD27 levels were studied
      longitudinally, the sCD27 levels correlated very well with remission and relapse
      of the disease. CSF sCD27 is useful as a tumor marker for PCNSL in
      immunocompetent patients, and is also useful to evaluate the effect of various
      types of treatment. Although there was a large cross-reactivity in the CSF sCD27
      levels between PCNSL and IND group, white blood cell count in the CSF is helpful
      to distinguish these two diseases.

PMID- 10935214
TI  - Design characteristics and clinical implementation of a newly designed indwelling
      carotid artery shunt.
AB  - The author has developed a new silicone carotid artery shunt (Loftus carotid
      endarterectomy shunt, Integra NeuroCare, Plainsboro, New Jersey) which offers
      several advantages over previously available commercial products. It is designed
      as an indwelling 15 cm (short) shunt, without an external loop. The silicone
      material makes for simple insertion and the ends are beveled and tapered to
      minimize dislodgement of any atheromatous material. At its proximal end a built
      up bulb has been placed to facilitate securing by a Rummel tourniquet. At the
      distal end of the shunt no bulb is necessary. A broad black band has been applied
      to its center to allow for immediate visual inspection of shunt migration or
      misplacement. In contrast to previous designs, no metal reinforcement is
      necessary in this shunt. It is supplied in two sizes in a kit which also includes
      a pair of disposable scissors hooked on the end for easy shunt transection at the
      time of removal. The shunt is best accompanied by a specialized shunt clamp
      (Loftus shunt clamp, Scanlan Medical Instruments, St. Paul, Minnesota) which has
      been designed with atraumatic jaws to secure it with minimal closing force in the
      internal carotid artery and to prevent back-bleeding around it. Clinical
      experience with the shunt has been extensive and satisfactory. Both the shunt kit
      and the shunt clamps are now available for commercial distribution.

PMID- 10935215
TI  - Surgical management of intractable epilepsy associated with cerebral neurocytoma.
AB  - Neuronal neoplasms of the CNS constitute a rarely encountered group of tumors.
      This report concerns the surgical management of seizures encountered in four
      cases (ranging from 2 to 10 years-of-age at onset; consisting of two males and
      two females) of a recently recognized morphologically unique tumor, called
      'cerebral neurocytoma'. All patients were associated solely with intractable
      complex partial seizures. The tumor involved the temporal lobe in two cases, and
      the frontal in two. Magnetoencephalography (MEG) clearly demonstrated an
      accumulation of equivalent current dipoles originating from the interictal spikes
      on the cortex around the tumor. On intra-operative electrocorticography (ECoG),
      the epileptogenic zone was topographically distinct from the region of the tumor.
      No definite ECoG activities were observed at the tumor site, although this tumor
      did consist of small mature neuronal cells. Either a complete or a subtotal
      resection of the tumor and the epileptogenic cortex was performed and, post
      operatively, universal freedom from seizures was demonstrated in all patients. A
      histological examination of the epileptogenic cortex revealed the presence of
      minute cortical dysplasia or tumor involvement in the hippocampus. A resection of
      the epileptogenic cortex along with the tumor was thus found to improve the
      seizure outcome in patients with neurocytoma-associated epilepsy without inducing
      any identifiable neurological deficits attributable to the incremental resection.

PMID- 10935216
TI  - Assessment of quantitative computed tomographic cerebral perfusion imaging with
      H2(15)O positron emission tomography.
AB  - Assessment of quantitative cerebral blood flow on a conventional fast CT machine
      without the use of specialized equipment may be valuable in the investigation of
      acute stroke and head injury. We aimed to compare a single slice CT perfusion
      sequence with H2(15)O positron emission tomography using the sagittal sinus as an
      input function, a method that avoids unnecessary orbital irradiation. Eight
      patients were studied, two patients with gliomas, and six with arteriovenous
      malformations. The dynamic CT perfusion sequence was performed by acquiring the
      same 10 mm slice 10 times over 30 sec during a 50 ml bolus of intravenous
      contrast medium given at a rate of 7.5 ml sec-1 using a power injector. The CT
      perfusion studies were completed without complication. Co-registration was sub
      optimal in one patient. Overall the correlation between the two methodologies was
      encouraging with an average r2 value of 0.524 for individual analyses. When two
      patients with high flow arteriovenous malformations were excluded the average r2
      value increased to 0.640. The results of this CT perfusion methodology are
      encouraging. Having shown its feasibility, further studies in conditions with
      lower rates of cerebral blood flow are warranted.

PMID- 10935217
TI  - Elastase expression by infiltrating neutrophils in gliomas.
AB  - Polymorphonuclear neutrophil elastase is a neutral protease released by activated
      polymorphonuclear neutrophils and plays a crucial role in maintaining host
      defense. However, under certain conditions, this enzyme damages normal tissue and
      facilitates infiltration of tumor cells. In this study, surgical specimens were
      obtained from the tumor core and infiltrating margin of the glioma of 12 patients
      with astrocytoma of varying degrees of malignancy, and the specimens were tested
      for the presence of elastase by immunohistochemical analysis. Polymorphonuclear
      neutrophil elastase was not present in the tumor core of any of the 12 cases.
      Elastase was expressed in areas of tumor infiltration of the brain in all four
      glioblastoma cases, three of the four anaplastic astrocytoma cases, and none of
      the four low-grade astrocytoma cases. There was a higher percentage of elastase
      positive polymorphonuclear neutrophils in the infiltrating margin of tumors with
      greater degree of malignancy. Polymorphonuclear neutrophils are recruited to
      malignant gliomas, and the elastase released by these cells aids in the
      infiltration of gliomas.

PMID- 10935218
TI  - Muscle hypertrophy due to scarring of the S1 nerve root.
AB  - Segmental muscle enlargement occurs in a variety of neurogenic conditions. We
      present a patient with calf hypertrophy, likely produced by continuous
      neuromuscular irritability and compensatory type 1 and type 2 muscle fiber
      hypertrophy. The underlying lesion of the S1 nerve root was caused by scarring,
      which could be demonstrated by Gadolinum enhanced, fat saturated magnetic
      resonance imaging. Thus, the application of this technique is recommended in
      otherwise etiologically unclear cases of neurogenic muscular lesions in order to
      detect chronic nerve root pathology.

PMID- 10935219
TI  - Acquired cerebral arteriovenous malformation induced by an anaplastic
      astrocytoma: an interesting case.
AB  - High grade gliomas foster an environment rich in angiogenic factors that promote
      neovascularity. We report a case of a cerebral arteriovenous malformation, which
      developed in the setting of a high grade astrocytoma. The patient presented with
      complaints of confusion and left hemiparesis. An initial cerebral angiogram was
      normal. Repeat angiography six weeks later demonstrated an extremely vascular
      lesion with arteriovenous shunting involving the right thalamus and occipital
      lobe. Histopathologic evaluation of open biopsy and autopsy specimens
      demonstrated a high grade astrocytoma in association with an arteriovenous
      malformation. Immunohistochemical staining with VEGF was diffusely positive. A
      possible role for the hyperangiogenic environment of a high grade astrocytoma
      resulting in the development of an arteriovenous malformation is discussed.

PMID- 10935220
TI  - Usefulness of synaptophysin immunohistochemistry in an adult case of choroid
      plexus carcinoma.
AB  - Choroid plexus carcinoma in an adult case is a very rare tumor and difficult to
      differentiate from metastatic tumors. The authors report a case of a 49-year-old
      female with choroid plexus carcinoma who previously had multiple carcinomas. In
      this case, synaptophysin immunohistochemistry proved to be extremely helpful for
      the histological diagnosis.

PMID- 10935221
TI  - Laser-induced fluorescence detection of malignant gliomas using fluorescein
      labeled serum albumin: experimental and preliminary clinical results.
AB  - To delineate the tumor margins of malignant gliomas laser-induced fluorescence
      detection technique was applied using 5-aminofluorescein-albumin as the
      fluorescent dye. The 5-aminofluorescein was linked to serum albumin (= AFlc-SA)
      as a cumulative protein label using residualizing markers. In a C6-glioma model
      the biodistribution and pharmacokinetics of the injected dye were investigated by
      labeling the protein conjugate with 111In-DTPA. Twenty-four hours after
      intravenous injection of the dye, fluorescence was activated by an argon laser
      and inspected in the C6-gliomas. Histological examinations were performed to
      compare the microscopic margins of the fluorescence-stained tumors with
      hematoxylin/eosin. The tumor uptake 24 h after dye injection was 23-fold higher
      than in the surrounding brain. Fluorescence inspection under laser activation
      demonstrated clearly stained and sharply demarcated tumors. The microscopic
      borders of the tumors corresponded exactly with the fluorescence, also
      demonstrating intracellular tumor uptake of the dye. In a preliminary study,
      three patients with malignant gliomas were operated using laser-induced
      fluorescence detection technique after injection of AFlc-SA. In all patients, the
      borders of the malignant gliomas were clearly stained by AFlc-SA during surgery.
      Laser-induced fluorescence imaging using the albumin conjugate AFlc-SA may be a
      promising method for delineating tumor margins which are hard to detect under the
      operating microscope alone.

PMID- 10935222
TI  - Ultrasonic surgical system (SONOPET) for microsurgical removal of brain tumors.
AB  - We use the ultrasonic surgical system in the treatment of brain tumors such as
      meningioma, neurinoma, glioma, etc. SONOPET is a useful and safe ultrasonic
      surgical system for microsurgery. The outer diameter of the tip of ultrasonic
      surgical systems is usually 2.5 mm and the inner diameter 2.0 mm. However, the
      outer diameter of the SONOPET is 1.9 mm and the inner diameter 1.5 mm. Even in a
      deep site, because of the small diameter tip, the operation can be done easily.
      Further, the very thin outer diameter of the tip flue, 5 mm, makes it easy to
      operate in the deep site. The maximum amplitude of the distal end tip, which can
      be an important factor in tissue fragmentation, is 240 microns. It is said that
      the thinner tip breaks down easily, but by reducing metal fatigue the lifetime of
      the tip is longer and a larger amplitude can be obtained. As a result, hard
      tissue fragmentation becomes available even with a thinner tip. The handpiece is
      very light in weight, approximately 110 g, helping to reduce operator fatigue
      when in long term use. The weight is approximately one-half of conventional
      types. Because of the high efficiency of the electricity/vibration energy
      conversion rate, the handpiece does not heat up during the operation. Also, since
      water cooling is not necessary, the procedures before and after use are simple.
      Changing the handpiece during the operation is also easy.

PMID- 10935223
TI  - A comparative study of MIB-1 staining indices of gliomas measured by NIH Image
      analysis program and conventional manual cell counting method.
AB  - To evaluate the NIH Image measured MIB-1 staining index (SI) as a useful tool for
      the determination of proliferative activity of gliomas, MIB-1
      immunohistochemistry was performed on paraffin sections to estimate the
      proliferative activity of 50 gliomas. Five to eight RGB images at 200
      magnifications were acquired per sample in a Macintosh computer using a RD-175
      digital camera and Adope Photoshop program, followed by conversion of the RGB
      image to B (blue subtracted) and R (red subtracted) images and finally automatic
      cell counting of more than 1000 cells per sample by the NIH Image analysis
      program. The mean MIB-1 staining indices by both NIH count and visually assessed
      (manual) count respectively were 12.7% +/- 9.9% (mean +/- standard deviation) and
      12.6% +/- 9.9% in all gliomas (n = 50), 2.9% +/- 0.6% and 2.3% +/- 0.6% in grade
      I and II astrocytomas (n = 9), 10.7% +/- 8.9% and 11.1% +/- 9.0% in grade III
      gliomas (n = 17), 16.1% +/- 9.1% and 16.3% +/- 9.1% in glioblastoma multiformes
      (n = 20), 26.0% +/- 4.9% and 24.5% +/- 2.6% in other glial tumors (n = 4). These
      paired values were assumed to be identical, since the p value obtained by paired
      t-test in all gliomas was 0.905. We conclude that the MIB-1 staining index
      measured by NIH Image is reliable and universal.

PMID- 10935224
TI  - Long latency response of the mentalis muscle following transcranial magnetic
      stimulation with a circular coil in normal subjects.
AB  - Short latency response (SLR), middle latency response and long latency response
      (LLR) are elicited in facial muscles by transcranial magnetic stimulation.
      Although it has been said that the LLRs are elicited by the trigeminal nerve
      stimulation, a trigeminofacial reflex is recorded easily in normal subjects by
      the electrical stimulation in orbicularis oculi muscles as a blind reflex, but a
      trigeminal-facial reflex recorded in orbicularis oris, namely a snout reflex, is
      more difficult to record in normal subjects. The aim of this study is to
      demonstrate the LLR of lower facial muscles (mentalis muscle) by the transcranial
      magnetic stimulation, using a circular coil. The transcranial magnetic
      stimulations were performed over parieto-occipital scalp with frequencies of
      random and 0.3 Hz in 11 normal subjects and the responses in the mentalis muscle
      were recorded. The LLR of the mentalis muscle was recorded in all 11 subjects
      following SLRs. The latency, duration and LLR/SLR ratio were 37.4 msec, 20.3 msec
      and 9.1%, respectively. The waveform of the LLR varied trial to trial showing
      habituation with a stimulation of 0.3 Hz. At this time the LLR of the masseter
      muscle was not recorded following this transmagnetic stimulation. It was
      suggested that the LLR of the mentalis muscle is recorded by the transcranial
      magnetic stimulation of the trigeminal nerve with a circular coil. The ease and
      reliability of their recording make it possible to apply this LLR clinically as
      well as a blink reflex.

PMID- 10935225
TI  - Brain metabolic and ionic responses to global brain ischemia in the newborn dog
      in vivo: 1. Methodological aspects.
AB  - A variety of methods has been used in order to obtain a state of acute cerebral
      ischemia. Most of these methods suffered from drawbacks such as irreversible
      ischemia, difficult to obtain total ischemia and heart injury. The aim of this
      study was to develop a new method for induction of global or partial cerebral
      ischemia in the newborn dog at various post-natal ages. A multi-parameter
      monitoring system (MPA) measures the metabolic (mitochondria NADH
      oxidation/reduction state), hemodynamic (reflectance), ionic (extracellular
      potassium and calcium) and electrical changes (ECoG) continuously and
      simultaneously in the puppy's brain in vivo. A hole was made in the chest cavity,
      the two large arteries supplying blood to the brain, the brachiocephalic and the
      subclavian arteries (B + S) were isolated and occluded during the monitoring. In
      most of the animals, occlusion of these two arteries alone resulted in partial
      ischemia. For obtaining 100% ischemia, we occluded both the B + S arteries as
      well as the aortic arch. Immediately at the onset of ischemia, an increase
      (reduction) of NADH begins. During complete ischemia the average time until
      maximal increase was 4 min, compared to ischemia of up to 50% of the maximal
      reduction of the NADH where the average time was 1 min. After reperfusion of the
      brain, mitochondria recovery was very rapid and the average time until return of
      this parameter to its pre-ischemic level was 1.4 +/- 0.2 min. The ionic changes
      which occurred immediately upon the onset of ischemia were the accumulation of
      extracellular potassium ions was recorded. The rate of potassium ion accumulation
      was dependent on the severity of the ischemia (range 0.19 +/- 0.08-2.2 +/- 0.4 mM
      min-1). The increase in the extracellular potassium ion concentration occurs in
      two stages, an initial slow stage and a second rapid stage (13.0 +/- 1.8 mM). The
      results presented in this paper suggest and prove the usefulness of a new
      approach for global and partial ischemia in the newborn dogs. In addition, our
      results assess the brain metabolic, ionic, hemodynamic and electrical responses
      to brain ischemia in the puppies.

PMID- 10935226
TI  - MRI of acute experimental intracerebral hematoma.
AB  - The purpose of the study was to evaluate the ability of different MR-sequences to
      detect and delineate experimentally produced hyperacute intracerebral hematomas
      in rats. Twenty male Sprague-Dawley rats received a unilateral hematoma of
      various volumes by stereotactic injection of fresh autologous arterial blood into
      the right caudatoputamen. MRI was performed up to 30 min after-generation of each
      hematoma. We obtained coronal T2- and T1-weighted spin-echo images. Furthermore
      we acquired RF-spoiled 2D- and 3D-FLASH images. MR-images were evaluated for
      signal behavior, location, configuration, size, and volume of each hematoma on a
      dedicated work station. MR volumetry was correlated to volumetric data obtained
      from the serial stained histological sections. All hematomas produced signal
      abnormalities on all sequences in each case. In the majority of cases the
      hematomas were hypointense. RF-spoiled FLASH 2D- and 3D-sequences showed the best
      detection of the hematoma owing to their high sensitivity to susceptibility
      effects. The best correlation between MR- and histological volumetry was found on
      RF-spoiled FLASH 2D- (corr. 0.81), SE T2- (corr. 0.79), and T1- (corr. 0.74)
      weighted images. The lowest correlation index was found on the RF-spoiled FLASH
      3D-images (corr. 0.51). Signal loss of hematomas on gradient-echo images and--to
      a lesser extent--spin-echo T2-weighted images due to susceptibility effects can
      reliably delineate an acute state, whereas conventional MR scans of ischemic
      stroke may be normal. MRI may thus be the imaging modality of choice in patients
      with acute brain attack, especially when it is planned to perform diffusion and
      perfusion MRI before thrombolytic therapy.

PMID- 10935227
TI  - Protective effect of ginkgo extract on rat brain with transient middle cerebral
      artery occlusion.
AB  - It has been empirically known that Ginkgo extract is useful for reducing many
      symptoms associated with cerebral blood flow (CBF) insufficiency, but its
      mechanisms have been uncertain. In the present study, therefore, we gave Ginkgo
      extract to rats with per os digestion, and investigated its effect on CBF and
      ischemic brain damage with middle cerebral artery occlusion (MCAO). The treatment
      with Ginkgo extract (10 mg 100 g-1 rat) increased CBF in the normal condition,
      but the degree of increase in CBF was lesser during and after MCAO. TTC staining
      showed that infarct volume was reduced with Ginkgo treatment. TUNEL and HSP72
      immunostaining confirmed the protective effect of Ginkgo treatment reducing
      numbers of TUNEL and HSP72 positive cells. Immunohistochemical analysis showed
      that caspase-3 expression was less abundant in Ginkgo treated rats. The present
      results suggest that Ginkgo extract contains a substance which increases normal
      CBF and reduces ischemic brain damage.

PMID- 10935228
TI  - Neuroendoscopy in microvascular decompression for trigeminal neuralgia and
      hemifacial spasm: technical note.
AB  - Miocrovascular decompression is an effective treatment for trigeminal neuralgia
      (TN) and hemifacial spasm (HFS). A complete cure cannot be obtained, and
      additional adjuncts for extended use of endoscopy are needed. The use of an
      endoscope combined with the operating microscope can enhance the surgeon's
      ability to view deep structures during operation. We study the application of
      combined microsurgical and endoscopic techniques in 21 cases of HFS and 12 cases
      of TN. With these techniques the surgeon can explore the ventral aspect of the
      brainstem and cranial nerves without further retraction, can see the groove
      caused by compression of the offending artery, and can confirm the proper
      position of the prosthesis after attachment to the dura by fibrin glue. In HFS
      the most common offending vessels in 75% of cases were the posterior inferior
      cerebellar artery (PICA) and anterior inferior cerebellar artery (AICA) and in
      25% of cases the vertebral artery (VA). In trigeminal neuralgia the offending
      vessel in 60% of cases was the superior cerebellar artery (SCA), and in 40% of
      cases the AICA. The overall success rate was 97% with minimal morbidity 3%
      (facial palsy) and no mortality. The aim of this work is to study advantages and
      disadvantages of using endoscopy during microvascular decompression for TN and
      HFS.

PMID- 10935229
TI  - Immunohistochemical analysis of beta-catenin in N-ethyl-N-nitrosourea-induced rat
      gliomas: implications in regulation of angiogenesis.
AB  - Angiogenesis plays an important role in the development of malignant brain
      tumors. We postulated the involvement of beta-catenin, which is associated with
      not only cell adhesion but also tumorigenesis in some neoplasms, in angiogenesis
      in brain tumors. We performed an immunohistochemical analysis of beta-catenin for
      vascular cells (VC) in 45 N-ethyl-N-nitrosourea (ENU)-induced rat gliomas and rat
      normal brain tissues. As a result, beta-catenin was found concentrated in the
      vascular cell-cell junction and internal surface of the vascular lumen in all
      normal brains. In contrast, proliferating VC in tumors were stained homogeneously
      in the cytoplasms of 35 cases (77.8%), among which nuclear staining was also
      recognized in 12 cases (26.7%). The proliferative potential of VC, which was
      evaluated by nucleolar organizer region-associated argyrophilic protein (AgNOR),
      was higher in all types of tumors than in normal brains, and was basically in
      parallel with the degree of malignancy of the tumors. Thus, it was suggested that
      the tumor vessels proliferate under a relationship with the proliferative
      potential of the tumors, and the intracellular localization of beta-catenin is
      changed under the influence of proliferative potentials of VC. beta-catenin in
      normal VC is considered to maintain the polarity of the vascular structure, and
      thus aberrant localization of beta-catenin may result in the loss of structural
      polarity of the tumor vessels.

PMID- 10935230
TI  - Development of surgical confocal scanning microscope for intra-operative imaging
      of brain tumors using near infrared fluorescence: technical note.
AB  - We developed a confocal laser scanning microscope for intra-operative imaging of
      brain tumors using near infrared fluorescence. The quality of near infrared
      images of Indocyanine Green (ICG) was compared with the surgical confocal
      scanning (SCS) microscope and a conventional charge-coupled device (CCD) camera;
      we compared images of a tube filled with ICG, which was located in the mouse
      brain. Compared to the CCD camera, the SCS microscope could obtain a more precise
      image of ICG fluorescence through the brain tissue. In addition, the SCS
      microscope could image ICG fluorescence clearly in a relatively light room
      because of elimination of stray light, while the CCD camera required high
      darkness to obtain ICG images. The present SCS microscope can give useful intra
      operative imaging of brain tumors, particularly detection of residual tumor
      tissues that extend into normal brain tissues.

PMID- 10935231
TI  - [A radiological study of the cervical alterations in Down syndrome. New findings
      on computerized tomography and three dimensional reconstructions].
AB  - OBJECTIVE: We studied a large proportion of the population in our health district
      who have Down's syndrome to determine the incidence and variety of changes in the
      spine and to define the guidelines for preventive diagnosis advisable in relation
      to atlanto-axial instability, a common disorder in these patients. PATIENTS AND
      METHODS: First phase: a plain X-ray of the cervical spine in a neutral lateral
      projection and in flexion in 188 patients, measuring the atlanto-odontoid
      distance. Second phase: computerized tomography (CT) studies and three
      dimensional reconstructions in 25 patients (13.3%) chosen at random. The axial
      cuts from the upper portion of C3 to the occiput were 3 mm in thickness with 3 mm
      intervals and a standard reconstruction algorithm. RESULTS: The incidences of
      atlanto-axial instability with an atlodontoid distance (3)5 mm were not
      comparable with the published series. There was a lower incidence (4.2%), with no
      difference between measurements in flexion and in the neutral lateral views.
      There was a greater incidence of malformations than in other reports, including a
      rare case of os odontoideum and also constant asymmetry of the occipital condyles
      (100%) in the patients of the CT series and consequently instability of the atlas
      (96%) and off-centered odontoides (84%). CONCLUSIONS: The study showed that there
      was deficient asymmetrical development of the occipital bone, which caused
      different heights of the occipital condyles and led to cervico-cranial mal
      position. For study of the degree of error of position and congenital anomalies.
      We recommend replacing plain X-ray studies by CT with three dimensional
      reconstructions.

PMID- 10935232
TI  - [Epilepsies in an outpatient setting: a study of 150 cases].
AB  - INTRODUCTION: In this paper we present epidemiological data from a register of
      cases of epilepsy attended in the Centro de Especialidades of the Alboraya street
      in Valencia. The sample corresponds to a particular type of healthcare setting,
      halfway between the family doctor and the specialist hospital department, which
      has recently begun to be developed in Spain in the field of neurology. PATIENTS
      AND METHODS: The sample consisted of 150 patients who completed a questionnaire
      type protocol. RESULTS: The average age of the patients was 39.66 +/- 19.60
      years, slightly more in the men than in the women. There were slightly more women
      than men included in the study. The epilepsy was either long-term or of recent
      onset. The average age of onset was 25.42 +/- 21.35 years. More than two thirds
      of the sample, that is 108 patients (72%) had partly controlled disease. However,
      a considerable number of them were irregularly controlled and another group of 23
      (15.3%) were on polytherapy with three or more antiepileptic drugs. CONCLUSIONS:
      The data from this series of 150 cases is, in general, similar to that of other
      epidemiological studies done in Spain. However, it is noticeable that there is a
      high proportion of patients with problems of control, although this may be due
      simply to a bias in the selection. We hope that the publication of this new data
      will stimulate new studies to analyse the attention give to patients with
      epilepsy in this healthcare setting.

PMID- 10935233
TI  - [Transient global amnesia: a review of 58 cases].
AB  - INTRODUCTION: Transient global amnesia (TGA) is a clinical condition in which the
      etiopathogenesis is still not clear. The most generally accepted theory is of a
      vascular origin, although epilepsy or migraine have also been considered to
      possibly be the cause. OBJECTIVE: To make a retrospective review of the risk
      factors, etiopathogenesis and clinical characteristics of 58 patients with TGA.
      PATIENTS AND METHODS: The variables recorded were compared with those from two
      control groups: one of healthy individuals and one of patients with transient
      ischemic attacks (TIA). RESULTS: The average age of the patients with TGA was
      66.01 years. The risk factors included: arterial hypertension (58.62%),
      dyslipemia (15.51%) and migraine (8.62%). In three patients the EEG showed weak
      bilateral frontotemporal interference. Cerebral CT scans were done in all cases
      and were found to be pathological in 23, with lacunar multinfarct the commonest
      abnormality. With regard to patients with TIA, these were older (66.01 vs 72.94),
      smoked more (1.72% vs 12.06%) and a previous stroke was more frequent (8.62% vs
      31.03%). We did not find differences regarding dyslipemia, atrial fibrillation,
      arterial hypertension or cardiac ischemia. However, the prevalence of vascular
      risk factors was significantly higher in patients with TGA as compared to healthy
      controls. CONCLUSION: We suggest that the etiopathogenesis of TGA is probably a
      transient ischemic phenomenon triggered (or not) following an attack of migraine.

PMID- 10935234
TI  - [Aspects of neuropathy in mitochondrial diseases].
AB  - INTRODUCTION: The existence of neuropathy has been described in mitochondrial
      disorders such as MELAS, MERRF, Leigh's syndrome, the Kearns-Saye syndrome,
      myoneurogastro-intestinal encephalopathy and progressive external ophthalmoplegia
      and constitutes a basic component of the NARP (neuropathy, ataxia and retinosis
      pigmentosa). However, the general prevalence of the neuropathy and its
      characteristics within the mitochondrial encephalopathies is not well understood.
      OBJECTIVES: To characterize the neuropathy and try to establish a genotype
      phenotype correlation. PATIENTS AND METHODS: Within study guidelines, we made a
      retrospective study of 27 patients, diagnosed as having mitochondrial disease,
      who had had neurophysiological studies (EMG-ENG). In those in whom neuropathy had
      been found we analysed the clinical, neurophysiological and genetic
      characteristics. RESULTS: Neuropathy was present in 37% of the patients who had
      an average age of 13 years, ranging from 1 to 25 years. Syndromic diagnoses were:
      7 encephalomyopathies, one MELAS, one MERRF and one NARP. Four of the patients
      were classified genetically. In all but two of the patients the neuropathy was
      asymptomatic. The biochemical alterations seen were: deficit of Complex 1 in 3
      patients, of complex III in 3 patients, of complex IV in 2 and of pyruvate
      dehydrogenase in one patient. The type of neuropathy found was varied, with
      predominance of axonal-type motor neuropathy but no correlation with either
      biochemical defects or genetic diagnosis. CONCLUSIONS: Neuropathy is a common
      finding in mitochondrial disorders and probably is under-diagnosed. The axonal
      form predominates. We have not been able to establish correlations between
      phenotypes and genotypes.

PMID- 10935235
TI  - [Simultaneous micro-transplantation of fetal mesencephalic cells to the striate
      and substantia nigra pars reticulata in hemi-parkinsonian rats. A study of
      behavior].
AB  - INTRODUCTION: Microtransplantation of fetal dopaminergic cells has been used over
      the past ten years with good results in models of Parkinson's disease. OBJECTIVE:
      To evaluate the effect of microtransplantation of fetal dopaminergic cells
      'seeded' in the substantia nigra pars reticulata (SNpr) and striate (St)
      simultaneously. MATERIAL AND METHODS: The animals received a transplant or
      microtransplant of cells into the St and SNpr ipsilateral to the lesion in the
      substantia nigra pars compacta or to both regions. Depending on the site and
      technique used the following experimental groups were considered: I.
      Macrotransplantation to the St (n = 20); II. Microtransplant to the St (n = 20);
      III. Microtransplant to St + SNpr (n = 20); IV. Microtransplant to St + SNpr (n =
      20); V. Macrotransplantation to SNpr (n = 20); VI. Microtransplantation to SNpr
      (n = 20); and VII. Control (lesion only) (n = 20). The rotations induced by D
      amphetamine (5 mg/kg i.p.) and by apomorphine were studied 1, 2, 3 and 6 months
      and 3 and 6 months respectively after transplantation. Three months after
      transplantation we studied the motor asymmetry shown by the animals by means of
      the ladder test. RESULTS: The rotations were reduced in the groups with
      intrastriate transplantation. Comparison between the surgical techniques showed
      nonsignificant differences between them. The ladder test showed significant
      differences in use of the limbs in all experimental groups. Use of the left limb
      was significantly reduced in all groups. CONCLUSIONS: Modification of the
      rotations seems more sensitive to the site of transplant than to the technique
      used. It seems that the skills studied using the ladder test are not altered by
      the microtransplant technique.

PMID- 10935236
TI  - [Multiple sclerosis incidence in the Alcoi Health district. 12-year-long study
      (1986-1997)].
AB  - INTRODUCTION: To date, epidemiological studies on multiple sclerosis in Spain
      have been basically prevalence studies, and the data on incidence recorded have
      been the result of different methodologies, with no definition of the criteria
      for inclusion. OBJECTIVE: To carry out a study of incidence with prospective
      collection/review of cases over a prolonged period of time. PATIENTS AND METHODS:
      Over 12 years, between 1 March 1986 and 31 December 1997, we collected data
      prospectively for patients with a definite diagnosis of multiple sclerosis. The
      year of incidence was considered to be when the patient fulfilled clinical
      criteria for diagnosis of the disease. RESULTS: On 31 December 1997 in the Alcoi
      Health District there were 54 patients with clinically defined multiple sclerosis
      (a prevalence of 41.28 cases per 100,000 inhabitants). Of these, 45 patients were
      diagnosed during the period studied, with an average incidence of 2.82 cases per
      100,000 inhabitants per year. Only 15 patients were confirmed before 1986.
      CONCLUSIONS: This is the most prolonged study of the incidence of multiple
      sclerosis carried out in Spain. The figures found for incidence are in contrast
      to those found in previous years for prevalence and incidence. Analysis of the
      data suggests that the incidence of multiple sclerosis in the Alcoi district has
      changed and has increased since the second half of the 1980s.

PMID- 10935238
TI  - [A neuroepidemiological study in Beira, Mozambigue].
AB  - INTRODUCTION AND OBJECTIVE: The application of epidemiology to the field of
      neurology is relatively recent although it has become so relevant that it is
      currently recognized as a new specialty: Neuroepidemiology. The objective of our
      study was to study the morbid-mortality of neurological disorders. PATIENTS AND
      METHODS: We made a retrospective investigation of all the patients admitted to
      the Hospital Central de Beira, Mozambique, between 1 January 1996 and 30 June
      1999. The source of information used was the clinical histories and data of the
      Statistics Department. The basis used for classification of the disorders was the
      International Classification of Diseases, Ninth Revision-1CD 9CM (3 digits).
      RESULTS: We found that neurological disorders were fifth in the classification of
      morbidity and third in mortality. Trauma, infections and vascular causes--in that
      order--were the most important factors in the morbidity of neurological diseases.
      The highest mortality rate was seen with infections, vascular and neoplastic
      etiologies. In our study we found disorders which several investigators consider
      to be almost nonexistent in Africa, such as multiple sclerosis, subacute combined
      degeneration of the cord and myasthenia gravis amongst others. The morbidity and
      mortality found for neurological diseases are similar, in general, to those
      described in Africa. CONCLUSION: The importance of neurological disorders in
      healthcare means that it is essential to have a specialist available for their
      management.

PMID- 10935237
TI  - [The prevalence of multiple sclerosis in the Alcoi Health district].
AB  - INTRODUCTION: The epidemiological studies done in Spain in recent years show
      higher figures for the prevalence of multiple sclerosis than before. Spain is
      therefore now in the area with a high risk of contracting the disease. OBJECTIVE:
      We have made a new study to confirm the current prevalence of the disorder in the
      Alcoi Health District. PATIENTS AND METHODS: Between 1 March 1986 and the
      prevalence day, 31 December 1997 we recorded the patients with definite or
      probable multiple sclerosis, as defined on Poser's criteria, after intensive
      fieldwork and reevaluation of all possible patients by a neurologist from the
      Neurology Unit. On the prevalence day there were 130,786 inhabitants in the
      district. RESULTS: On the prevalence day we found 54 patients with definite
      multiple sclerosis and no patient with probable multiple sclerosis. The rate of
      prevalence was 41.28 cases per 100,000 inhabitants (95% CI: 31-53.6). During the
      study we counted an incidence of 45 cases with an average rate of 2.82 cases per
      100,000 inhabitants per year. We also describe the clinical characteristics of
      the patients. CONCLUSIONS: The rate of prevalence found is much higher than that
      described for the district in studies using similar methodology. This increase,
      together with the discrepancy between the incidence found and the prevalence,
      makes us consider that possibly the prevalence has increased in recent years.

PMID- 10935239
TI  - [Gabapentin used in 559 patients with partial seizures. A multicenter observation
      study. Spanish Gabapentin Work Group].
AB  - INTRODUCTION: Gabapentin (GBP) is a new antiepileptic drug whose efficacy and
      tolerability have been evaluated in clinical trials, although there is little
      data on its use in everyday clinical practice. OBJECTIVES: To evaluate the
      characteristics of GBP in an observational study when used in patients with
      uncontrolled partial seizures. PATIENTS AND METHODS: An open multicentric study
      in which GBP was used in 559 patients of over 12 years of age with uncontrolled
      partial crises in whom the efficacy, tolerability and quality of life (QOLIE-10)
      over a period of 6 months were analysed. RESULTS: The response rate (> 50%
      reduction in seizures) was 71% with 35.3% seizure-free patients. There were no
      differences related to age, aetiology, previous frequency of seizures or duration
      of the epilepsy. In 18.8% there were adverse effects (somnolence, dizziness,
      headache, blurred vision, diplopia and nausea), which were generally well
      tolerated, but in 4.5% of the patients led to the drug being suspended. In the 65
      patients in whom quality of life was evaluated there was improvement, both
      overall and in each aspect studied. CONCLUSION: Under normal conditions of
      everyday clinical practice, GBP is an effective drug which is well tolerated by
      adults and adolescents with refractory partial seizures.

PMID- 10935240
TI  - [A brief questionnaire for the diagnosis of maladaptive behavior disorders in
      adolescents aged between 12 and 16 years of age].
AB  - OBJECTIVE: To standardize and to determine the structural validity of a conduct
      disorder self report questionnaire in adolescents. PATIENTS AND METHODS: One
      hundred ninety, 12 to 16 year old male participants from the different
      socioeconomic status were randomized selected from educational institutions of
      Medellin City, Colombia. A quantitative self report questionnaire, with a
      discrete (0-3) item scored scale, based upon the DSM-IV criteria A symptoms for
      conduct disorder was applied to the sample. Reliability analysis using alpha
      item/scale Cronbach's coefficient was calculated, and a factor analysis with a
      maximum likelihood method of extraction and VARIMAX rotation was developed.
      RESULTS: The standard obtained scores defined the presence and distribution of
      the symptoms of conduct disorder in an adolescent normal population. Reliability
      alpha Cronbach's coefficient for 14 items was 0.86. Three stable factors, which
      explained 53.9% of the variance, were found. First factor was serious violation
      of rules and explained 32.9% of variance, second factor was violence, which
      explained 10.9%, and the third factor was cruelty which explained 10.1% of the
      structure (Goodness-of-fit chi 2 = 34.6; df 25; p = 0.09). Conduct disorder
      questionnaire had a strong internal consistency and multidimensional structure,
      which would allow that it could be used in clinical and epidemiological
      researches with adolescent population.

PMID- 10935241
TI  - [Acute cerebrovascular accident associated with drepanocytosis complicated by
      pneumococcal meningitis in two children].
AB  - INTRODUCTION: Between 6% and 17% of the patients with drepanocytosis will have an
      acute cerebrovascular accident (ACVA). Precipitating factors have been described
      including bacterial meningitis, upper respiratory tract obstruction, dehydration,
      intense exercise, postoperatively, and hypoxia due to altitude. CLINICAL CASES:
      We report two Negro children with drepanocytosis who, at the ages of 8 and 20
      months, had pneumococcal meningitis complicated by an ACVA. The 20 month old boy
      had been previously diagnosed as having drepanocytosis; the 8 month old girl was
      diagnosed when she was admitted to hospital with meningitis. In both cases the
      clinical features of the ACVA were focal epileptic seizures followed by
      hemiplegia. On cranial CT and MR regions of focal ischaemia of the hemisphere
      were observed. The boy of 20 months made an excellent recovery with no long term
      sequelae. The 8 month old girl had severe permanent sequelae: hemiparesia,
      blindness, mental deficiency and epileptic encephalopathy. CONCLUSIONS: We
      present two Negro children with drepanocytosis who had ischemic ACVAs, a common
      complication of the disease, during the course of pneumococcal meningitis but
      with very different clinical courses. Recent increases in immigration will mean
      that previously rare illnesses will be more commonly seen in our environment, and
      should be considered in the differential diagnosis.

PMID- 10935243
TI  - [Non-dystonic torticollis. A report of a case secondary to retropharyngeal
      abscess].
AB  - INTRODUCTION: There are many causes of acquired non-dystonic torticollis:
      cervical bony anomalies, nasopharyngeal infections, tumours of the spinal cord,
      and posterior fossa, ocular, vestibular and gastrointestinal disorders. In
      children, non-dystonic is commoner than dystonic torticollis, except for in
      adverse reactions to drugs. Palatopharyngeal lesions due to a rigid object being
      impacted in the mouth (pencil-injury) are common in childhood. Many are not
      dangerous and require no specific treatment, although there is a risk of
      perforation of the pharyngeal wall and of a retropharyngeal abscess. CLINICAL
      CASE: We report the case of a 9 year old boy who was seen in the Emergency
      Department complaining of fever present for four days and progressive cervical
      rigidity for the past two days which did not improve with myorelaxant drugs. A
      lateral X-ray of the spine showed prevertebral air and on the oesophagogram a
      fistula tract was seen. On further questioning the boy admitted that a stick he
      had had in his mouth had caused damage the day before his fever started. CT
      showed the extent of the abscess. After a week of treatment with antibiotics and
      corticosteroids the clinical features disappeared, and on CT after two weeks it
      was seen that the abscess had resolved. CONCLUSIONS: We suggest that a lateral
      radiograph of the neck should be done in cases of acquired torticollis, even
      though there is no suspicious clinical history. Early diagnosis and treatment of
      retropharyngeal abscesses is essential to prevent extension to adjacent
      structures, and atlanto-axoid subluxation secondary to the oedema and tension of
      the ligaments caused by the abscess (Grisel's syndrome).

PMID- 10935242
TI  - [Uremic myopathy].
AB  - INTRODUCTION: The neurological features of chronic renal failure are very varied.
      Uremic myopathy is a controversial condition. In most cases it is related to the
      secondary hyperparathyroidism which these patients develop, and its
      characteristics are superimposed on their osteomalacia myopathy. CLINICAL CASES
      AND CONCLUSIONS: We report two patients with terminal chronic renal failure on
      hemodialysis who complained on difficulty with walking. The clinical findings,
      laboratory and neurophysiological investigations and the histopathological report
      of the muscle biopsy were similar to those of osteomalacia myopathy. The muscle
      weakness of patients with terminal chronic renal failure is related to many
      factors. The most important of these is the secondary hyperparathyroidism which
      leads to osteomalacia myopathy. On muscle biopsy there was isolated fibre
      necrosis of both types 1 and 2 (case 1) and of type 2 alone (case 2), which is
      considered to be the commonest finding. Although treatment with high doses of
      vitamin D3, or its hydroxylated metabolites, has been recommended, it was not
      effective in our patients.

PMID- 10935245
TI  - [Moyamoya disease and primary intraventricular hemorrhage in an adult patient. A
      case report].
AB  - INTRODUCTION: Moyamoya disease is generally considered to be paediatric
      cerebrovascular pathology, but in some cases the symptoms are seen in adults.
      Primary intraventricular hemorrhage, as a consequence of this disorder, is rare.
      One should be clear as to the diagnostic and neuroimaging criteria of 'definite
      moyamoya disease'. CLINICAL CASE: A 52 year old man with a family history of two
      brothers having died of hemorrhagic cerebrovascular accidents and a personal
      history of headaches for many years and arterial hypertension. He was sent to us
      with stroke, headache, neck stiffness+4, disorientation in time and space and
      stuporous. On cranial CAT scan a small left intraventricular subependymal
      hemorrhage and intraventricular hemorrhage were seen. Cerebral angiography showed
      the angiographic pattern of moyamoya disease and the arterial circulation of the
      posterior territory was highly developed and thus supplemented the blood supply
      to the brain. CONCLUSION: In few of the rare occurrence of this disorder in our
      setting and as a cause of primary intraventricular hemorrhage, we reviewed
      certain neuroradiological peculiarities of interest, such as the evolution,
      diagnostic criteria, angiographic classification and differential diagnosis of
      the moyamoya syndrome in relation to our case.

PMID- 10935244
TI  - [Neuropsychological evaluation in a case of multiple sclerosis].
AB  - INTRODUCTION: The neuropsychological assessment of patients with multiple
      sclerosis (MS) may be diagnostically useful to provide a patient's cognitive
      profile, to observe the spread of the deficit and to identify the peculiar areas
      that are more or less affected, in order to plan a long-term management and
      treatment. CLINICAL CASE: In this article, we present a case of cognitive
      dysfunction associated with a progressive MS in a 54 years woman, which was
      diagnosed six years ago. The magnetic resonance imaging showed demyelinating
      lesions at the periventricular region, with left predominance, and in the
      protuberance with signs of cortico-subcortical atrophy. We performed
      neuropsychological assessment of the main cognitive areas: orientation,
      attention, information processing, memory, general intelligence functioning,
      language, arithmetic, visual-spatial functioning, motor, executive functioning
      and personality. CONCLUSIONS: The results obtained point out serious alterations
      in the information speed processing, long term memory, motor, executive
      functioning and personality. This results go in a concordant way with the results
      reported in the consulted bibliography. Likewise, it is commented the resemblance
      of the cognitive deficit related to a pattern of subcortical dementia.

PMID- 10935246
TI  - [The application of transcranial magnetic stimulation in neuropsychological
      investigation].
AB  - OBJECTIVE: In this review we describe the main studies in which transcranial
      magnetic stimulation (TMS) has been used in the study of superior cognitive
      function. DEVELOPMENT: The various studies published in the literature show that
      TMS can modulate neuropsychological processes such as attention, different types
      of memory such as working memory, declarative memory, memory of procedures and
      language. In most cases TMS acts on the different cognitive abilities blocking or
      making them difficult. Thus TMS may be used as a method of causing transient
      lesions bringing the relationship brain-conduct to a dimension of cause and
      avoiding certain limitations of the classical method for creating lesions. The
      positive effects of TMS in certain tasks involving language and memory has also
      been shown. The latter offer new possibilities of future application in cognitive
      rehabilitation. CONCLUSIONS: TMS has an obvious effect on neuropsychological
      functions. Over the past ten years studies in this field have increased
      progressively. At the present time the results obtained by using TMS in cognitive
      neuroscience are of a basic type, limited to experimental laboratory work. It has
      mainly been used on normal persons. However, it cannot be long before it is used
      clinically in neuropsychological patients.

PMID- 10935247
TI  - [The CNS amyloid].
AB  - INTRODUCTION: In this article we wish to review the most relevant pathogenic
      aspects and histological characteristics of the deposition of amyloid in the
      central nervous system (CNS). DEVELOPMENT: The beta A4, a product of protein APP,
      codified on chromosome 21, is related to sporadic cerebral amyloid angiopathy not
      associated with dementia, Alzheimer's disease, senile dementia of Alzheimer type
      or Down's syndrome, whilst a specific mutation on the 693 codon of the gene which
      codifies beta-APP is related to hereditary haemorrhage with Dutch-type amyloid
      angiopathy. The gene which codifies cystatin C, a member of the family of
      cystatin genes grouped on chromosome 20p11.2, undergoes specific mutation giving
      rise to a mutant protein which, at the position 68, substitutes leucine for
      glutamine. The mutant cystatin C has a greater tendency to aggregation when the
      temperature is increased. This pathogenic molecular mechanism underlies cases of
      amyloidosis due to hereditary type cystatin C, considered to be a systemic
      amylosidosis. The formation and deposition of amyloid may also occur in other
      neurodegenerative diseases of animals and humans in relation to the accumulation
      of abnormal isoforms of the prion protein, especially in Gerstman-Straussler
      Scheinke's disease and the Japanese type of prion cerebral amyloid angiopathy.
      The fact that these aberrant isoforms mostly undergo conformational changes
      involving a shift from alpha-helix to beta-sheet structure is basic to the
      amyloidogenesis of prion disease. CONCLUSIONS: Amyloid is a family of proteins
      which is physically, chemically and structurally related, with common
      histochemical characteristics. In the CNS it is deposited in the vessel walls and
      parenchyma with topographic patterns and morphological differences according to
      the different disorders in which the amyloid is involved. Only neuropathological
      studies will enable us to discover its true incidence in senility with or without
      clinical features of dementia, and with or without haemorrhagic changes.

PMID- 10935248
TI  - [Integrated program of psychogeriatric care].
AB  - INTRODUCTION: At the present time there is considerable controversy over the
      course to follow in attention to patients with psychogeriatric disorders. Rapid
      diagnosis and maintaining the patients in their homes are the basic objectives of
      the policy of sharing responsibility among those involved. DEVELOPMENT: We review
      the bibliography and suggest a form of attention based on experience acquired in
      the dementia evaluation unit of the Programme Vida als Anys of the Generalitat de
      Catalunya. The model described is based on making the diagnosis in the patient's
      home, giving support to the family and integrating the patient into a follow-up
      unit, with a person responsible for evaluating and resolving the needs of both
      patient and family as they arise. In order to carry out this programme, the
      attention must be given by multidiscliplinary units with the necessary resources.

PMID- 10935249
TI  - [Intravascular lymphomatosis: a rare etiology of recurrent cerebral ischemia].
AB  - INTRODUCTION: Intravascular lymphomatosis is a rarely seen clinicopathological
      condition. OBJECTIVE: To review the literature on cerebral ischemia and
      intravascular lymphomatosis. DEVELOPMENT: Intravascular lymphomatosis is usually
      caused by an uncommon type of non-Hodgkin lymphoma, usually of B cells,
      characterized by the localization of predominantly neoplastic cells within the
      small calibre blood vessels (arterioles, venules and capillaries). Therefore, it
      tends to cause multifocal vascular occlusions, with symptoms generally limited to
      the central nervous system, in the form of recurrent, multifocal cerebral
      infarcts--one in every 5,000 consecutive cases is usually of this aetiology--or
      rapidly progressive encephalopathy. Cerebral or meningeal biopsy, or biopsy of
      peripheral nerve, muscle, adrenal or lymphoid tissue, prostate or lung is usually
      diagnostic. The differential diagnosis is with vasculitis, multi-infarct
      dementia, occult neoplasia or infections. In spite of starting suitable treatment
      with chemotherapy or radiotherapy, the average survival from onset of symptoms is
      usually four months. CONCLUSION: Intravascular lymphomatosis should be taken into
      account in the differential diagnosis of repeated cerebral ischaemia of unusual
      aetiology.

PMID- 10935250
TI  - [Indications of the surgical treatment of epilepsy].
AB  - INTRODUCTION: The surgery of epilepsy is expanding considerably all over the
      world. It is becoming a standard treatment in patients who are resistant to
      conventional medical treatment. DEVELOPMENT: In this article we explain the
      methodology used by the authors and suggest concepts regarding the epileptogenous
      area. We also explain the procedures used in neuroimaging and neurophysiology
      studies. CONCLUSIONS: Good methodology, such as that used by the authors, results
      in up to 65% of the patients in whom amygdalo-hippocampectomy is done becoming
      completely seizure-free. Amygdalo-campectomy is the most specific indication in
      mesolimbic temporal epilepsy, which is also the main indication for the surgery
      of epilepsy.

PMID- 10935251
TI  - [The evidence for primary axonal loss in multiple sclerosis].
AB  - INTRODUCTION: At what stage in the pathogenesis of multiple sclerosis (MS) does
      the damage to axons occur, and why should there be any axon loss at all in what
      is thought to be principally an axon sparing demyelinating disease? A recently
      described new technique for investigating axon damage depends for its ability on
      the immunoreactivity of amiloid precursor protein (APP), which has been shown to
      be more sensitive than silver stains for detecting damaged axons. DEVELOPMENT: We
      used APP immunoreactivity as a method to investigate whether axon damage occurs
      in acute MS lesions. The results of our APP staining showed that the expression
      of APP in MS lesions is associated with acute MS lesions and the active border of
      less acute lesions. There was little, if any, APP expression in the chronic
      lesions. If we accept that the APP staining represents irreversible damage to
      some axons, the next question is what factors are responsible for mediating
      damage to axons in MS? Matrix metalloproteinases (MMP) are expressed by
      macrophages in acute MS lesions and in the active borders of active chronic
      lesions. The injection of highly-purified MMP into the brain results in
      demyelination, blood-brain barrier breakdown, and axonal loss. Moreover, the
      inhibition of the MMP activity reduces the severity of MS-like lesions in
      experimental models. Thus the properties and distribution of these enzymes make
      them rational targets for therapeutic intervention. CONCLUSION: Whatever
      mechanism proves to be responsible for axonal damage in MS, it is clear that this
      disease should, perhaps, be more appropriately recognized as a primary
      demyelinating entity with associated primary axonal loss.

PMID- 10935252
TI  - [Some aspects of histopathology in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is an inflammatory demyelinating disease of
      the central nervous system. Inflammation, demyelination and a variable degree of
      oligodendrocyte loss belong to the key features of this disorder. DEVELOPMENT: In
      MS plaques, different stages of demyelinating activity can be distinguished based
      on the presence of myelin proteins within the cytoplasm of macrophages, the
      degree of remyelination and the expression of macrophage activation antigens.
      Additionally, different patterns of oligodendrocyte loss and preservation can be
      found indicating a heterogenous pathogenesis of demyelination in MS. In the
      present report, we present criteria for classification of demyelinating activity
      as well as patterns of oligodendrocyte pathology.

PMID- 10935253
TI  - [The pathogenic role of inflammation in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis (MS) is characterized by the presence in the
      central nervous system (CNS) of perivascular inflammatory infiltrates containing
      auto-reactive T and B cells and activated macrophages thus indicating that MS is
      a T cell-mediated CNS-confined chronic inflammatory demyelinating disease in
      which the ultimate effector cell is the activated macrophage. DEVELOPMENT: The
      inflammatory process, leading to patchy demyelination and axonal loss, is mainly
      sustained by pro-inflammatory cytokines that modulate at different levels the
      pathogenic process underlying MS. Cytokines can 1. Sustain the 'putative' CNS
      confined inflammatory process leading to the development of myelin-specific T
      cells; 2. Activate circulating myelin-specific T cells and shape their repertoire
      (Th1 versus Th2 pattern); 3. Induce the CNS recruitment of non antigen specific T
      cells and myelinotoxic effector cells (monocyte/macrophages) from the periphery,
      and 4. Cause direct oligodendrotoxicity (TNF alpha) or induce the secretion of
      myelinotoxic substances. The present chapter will focus on the mechanisms
      sustaining the activity of pro-inflammatory cytokines in MS pathogenesis.

PMID- 10935254
TI  - [In-vivo assessment of multiple sclerosis pathology: the role of neuroimaging
      techniques].
AB  - Although the correlations between magnetic resonance imaging (MRI) findings and
      long-term disease evolution range from poor to moderate', conventional pre- and
      post-contrast MRI provides sensitive and reliable measures to monitor multiple
      sclerosis (MS) activity over time. The application of non-conventional
      techniques, such as magnetization transfer imaging (MTI), proton magnetic
      resonance spectroscopy (MRS) and diffusion-weighted imaging (DWI), can increase
      the pathological specificity of MRI findings and, as a consequence, improve the
      relationship with the clinical evolution of the disease. These techniques also
      enable us to quantify the subtle abnormalities occurring in the so-called normal
      appearing white matter, thus allowing to achieve a more accurate assessment of MS
      burden. Some of the aforementioned techniques have already shown their value for
      assessing MS dynamics, whereas other still need to go through a more complete
      validation process prior to any extensive clinical application in MS. The use of
      multiparametric MRI approaches, including both conventional techniques and new
      methods able to assess the macro- and microscopic disease burden and to
      characterize the individual lesion intrinsic nature, should improve our ability
      to study in vivo the pathology of MS.

PMID- 10935255
TI  - [Axonal damage in multiple sclerosis].
AB  - The presence of axonal lesions in plaques of demyelination in patients with
      multiple sclerosis (MS) has been known for many years. Traditionally it was
      believed that axonal loss occurred in chronic lesions. However, demonstration of
      pathological degeneration in active plaques, use of new resonance techniques such
      as spectroscopy or the transfer of magnetization, showing axonal damage in white
      matter of apparently normal aspect, and the presence of axonal neurofilaments in
      the cerebrospinal fluid during the episode has made it necessary to reconsider
      the contribution made by axonal damage to the pathogenesis of MS. Besides, recent
      studies have shown that a factor present in the cerebrospinal fluid of patients
      with MS may contribute to the induction of neuronal apoptosis. These facts, apart
      from their pathogenic implications and consequent clinical repercussions, will
      affect investigation of alternative treatments for this disorder, and by means of
      clinico-immunoradiological correlation will help to define the prognosis of the
      course of the disorder in these patients.

PMID- 10935256
TI  - [Approach to quality of life changes in patients with multiple sclerosis].
AB  - INTRODUCTION AND OBJECTIVES: Multiple sclerosis (MS), as a chronic, incurable and
      often severely disabling disease, greatly affects patients normal life. The
      objectives of the study are to analyze which aspects of daily life are more
      affected by the disability and to investigate whether the degree of support
      demanded by patients is related to their level of incapacity. PATIENTS AND
      METHODS: Group of 60 ambulatory patients with Poser defined MS, mean age of 44.5
      years, Expanded Disability Status Scale (EDSS) of 3.1, and average period of
      disease evolution 13.2 years. Test instrument was a structured 12 items
      questionnaire given during a visit to the attending physician and regarding
      social and family aspects, financial needs, professional life and emotional well
      being. RESULTS: 58.3% of the professionally active patients had to give up their
      jobs; 8.3% experienced changes in their marital status and general family life
      somewhat changed in 41.7% of the cases due to either physical or psychical
      disease consequences. Social relationships were altered in 68.2% of the cases;
      43.3% required some level of economical support, and 80% went through episodes of
      emotional distress. CONCLUSION: Statistically significant relationships exist
      between level of incapacity and professional and social life changes but not with
      family life changes, emotional alterations and level of support required.

PMID- 10935257
TI  - [A study of various scales of fatigue and impact on the quality of life among
      patients with multiple sclerosis].
AB  - OBJECTIVES: To explore fatigue in multiple sclerosis and evaluate the specificity
      of three fatigue scales in this condition: the fatigue severity scale, the
      specific fatigue scale and the fatigue impact scale. MATERIAL AND METHODS: We
      sent out 60 questionnaires with the three scales and the quality of life scale,
      the Nottingham Health Profile, to patients with multiple sclerosis as clinically
      defined by Poser's criteria. Answers were received to 58 questionnaires and the
      data correlated by Sperman's correlation and the Student t test, with demographic
      variables (age, age of onset and sex) and clinical variables (clinical form, time
      the disease was present, period of time since the previous episode and Kurtzke
      scale (EDSS). RESULTS: Fatigue was present in 78% of the patients. There was
      correlation between fatigue severity scale and EDSS, pyramidal function,
      cerebellar function, the period of time the illness was present and the clinical
      form. We found that the specific fatigue scale is independent of EDSS. The
      fatigue impact scale was correlated with the EDSS apart from the questions
      concerning cognitive function. CONCLUSIONS: Fatigue is a common symptom of
      multiple sclerosis which has an independent effect on cognitive function. It is
      also related to involvement of the pyramidal and cerebellar systems, and depends
      on the degree of disability and time the disease has been present. The specific
      fatigue scale is a good tool for exploration of this symptom of multiple
      sclerosis.

PMID- 10935258
TI  - [Treatment of multiple sclerosis and quality of life].
AB  - INTRODUCTION AND DEVELOPMENT: At the present time, the treatments available for
      multiple sclerosis (MS) are only partially effective, often expensive and with
      side-effects. This means that there are other variables in the use of drugs which
      may affect the quality of life. In this respect, some treatments may maintain the
      patient's quality of life rather than improving it. The quality of life test may
      serve as an instrument or tool to compare different treatments and permit
      suitable optimization of the equilibrium between risk and benefit, and the
      possible relation to the cost of the illness. There is no universally accepted
      test for quality of life in MS. CONCLUSION: We have tried to evaluate existing
      tests and find which best measures the specific aspects of quality of life in
      patients with MS.

PMID- 10935259
TI  - [Scales for functional assessment in multiple sclerosis].
AB  - OBJECTIVE: To review the characteristics which should be met by the scales for
      functional assessment of patients with multiple sclerosis in relation to the
      degree of invalidity, incapacity and handicap. DEVELOPMENT: The functional scales
      for neurological patients which we review are Barthel's index, the PULSES Scale,
      Katz Index, Rankin Scale, Kenny Scale, Donaldson Scale, Garno Scale, ISS
      (Incapacity Status Scale) FAM Scale (Functional Assessment Measure), Hauser's
      Ambulant Index, Cambridge Scale (CAMBS) and London Handicap Scale (LHS).
      CONCLUSIONS: There is no single scale for the functional assessment of patients
      with multiple sclerosis which covers all the aspects to be assessed. Therefore it
      is necessary to use a combination of various scales to find exactly the degree of
      invalidity, incapacity and handicap. From our point of view the scales with which
      this assessment may be done are--apart from the usually used NRS (Neurological
      Scoring System) and EDSS--the Hauser Index, Cambridge Scale and London Handicap
      Scale.

PMID- 10935260
TI  - [Magnetic resonance imaging correlates of cognitive dysfunction in patients with
      multiple sclerosis].
AB  - INTRODUCTION AND DEVELOPMENT: Studies with conventional magnetic resonance
      imaging (MRI) support the hypothesis that cognitive impairment in multiple
      sclerosis (MS) patients is related with the lesion burden. Patterns of frontal
      lobe cognitive decline were also found to be related with the corresponding
      regional lesion load, although the total lesion load on T2-weighted MRI scans of
      the brain seems to be more relevant in determining frontal lobe deficits. Other
      non-conventional MRI techniques with a higher specificity to the heterogeneous
      substrates of MS pathology, such as the assessment of hypointense lesion load on
      T1-weighted scans and the histogram analysis of magnetization transfer ratio
      maps, have recently been applied to MS cognitive studies. CONCLUSIONS: Results
      from these studies suggest that three factors play a role in the pathogenesis of
      MS dementia: the burden of MS lesions, the severity of the pathological damage
      within individual lesions and that of the normal-appearing white matter.

PMID- 10935261
TI  - [The rational basis of the newer treatments used in multiple sclerosis].
AB  - INTRODUCTION: Multiple sclerosis is a disease known as a clinicopathological
      entity since more than a century, but its ethiology remains unknown till today.
      OBJECTIVE: In this paper the pathogenic mechanisms of this disease are reviewed;
      this knowledge has permitted and will permit in the very next future to develop
      new treatments more efficacious. DEVELOPMENT: All the knowledge from the
      different areas related to multiple sclerosis, neuropathology, neuroimaging,
      genetics, epidemiology, virology and immunology, are reviewed and integrated. The
      integration of all these information has permitted to elaborate a pathogenic
      hypothesis, according to which, multiple sclerosis most probably is an autoimmune
      disease, that will affect persons with genetic susceptibility after exposition to
      one or more environmental agents, being unknown the responsible antigen, most
      probable one or more viruses. The new treatments, although not aiming to the
      causal agent, intend to interfere with some links involved in the pathogenesis of
      the disease, attempting to slow the progression, if not to cure the disease.
      CONCLUSIONS: Today, is possible to approach the development of new treatments of
      multiple sclerosis with a scientific basis, although the ethiology is unknown and
      undoubtedly the pathogenic hypothesis is incomplete.

PMID- 10935263
TI  - [Cerebral death and bioethics].
AB  - INTRODUCTION: Brain death has been a topic of great interest for clinicians
      throughout the history of Neurosciences. There are so many different ideas about
      this topic that it has been necessary to constantly define further the criteria
      and medical decisions applicable in this field. Also about this matter there are
      a set of cultural, philosophical and religious aspects as well as autonomous
      principles in the people involved in such an event. Questions and dilemmas are
      still present in the individuality of every case and especially in terms of
      management of information and circumstances that define brain death. DEVELOPMENT:
      This essay tries to analyze the medical and historical issues around death and
      its relation to the context of brain death as such. There are also a series of
      reflections supported by the current bioethical thoughts that are identified with
      a cultural framework that is crucial to acknowledge the way in which the doctor,
      the family and society approach an event such as brain death. In spite of all the
      development of diagnostic technology and the extremes of the futility and extreme
      cruelty of treatments; there are still open questions that require to be looked
      into with objective criteria and scientific rigor. CONCLUSION: We should not put
      aside bioethical principles that are inherent to human quality and dignity that
      touch the sensitivity of those who give out the information and those who receive
      it within this process of interaction between the medical staff and the family.

PMID- 10935262
TI  - [Rationale for an early treatment of multiple sclerosis].
AB  - Multiple sclerosis (MS) is a demyelinating disease of the central nervous system
      (CNS) of unknown etiology. Its pathological hallmark is the presence within the
      CNS of inflammatory infiltrates containing few autoreactive T cells and a
      multitude of pathogenic nonspecific lymphocytes. Based on that, various non
      specific immunosuppressive agents have been tested with marginal benefits on the
      natural evolution of the disease and frequent short- and long-term adverse
      effects. Moreover, due to their unfavourable profile, these therapies have been
      usually limited to patients with progressive courses or high clinical activity.
      The recent approval of IFN beta and Copolymer 1, as therapies able to modify the
      disease course in relapsing-remitting and secondary progressive, as well as the
      available immunopathological and clinical data suggesting that the early
      treatment of MS with safe profile immunomodulatory drugs could be advantageous
      compared to late treatments, supports the 'putative' relevance of these new drugs
      in the early treatment of MS patients. However we must wait for the results of
      ongoing clinical trials to define if such an early treatment has substantial
      advantages compared to late treatment.

PMID- 10935264
TI  - [Prognostic value of the Spetzler and Martin scale for arteriovenous
      malformations treated surgically].

PMID- 10935265
TI  - [Cerebellum and cognitive functions].

PMID- 10935266
TI  - [Tropical spastic paraparesis and mixed infection due to Treponema pallidum and
      HTLV-I].

PMID- 10935267
TI  - [Cocaine and cerebrovascular diseases in young adults].

PMID- 10935268
TI  - The paratyphoid salmonellae.
AB  - The paratyphoid Salmonella bacteria, comprising more than 2,000 serovars or
      serotypes, are a major problem to the poultry industry. This is largely the
      result of entry of the bacteria into the human food chain. Human infection takes
      the form of a gastroenteritis, which in highly susceptible individuals can result
      in death. Some strains of certain serotypes have the capacity to produce
      morbidity and mortality in very young chickens. In adult birds, some serovars
      become localised in the reproductive tract with concomitant vertical
      transmission. The association between S. Enteritidis and table eggs has produced
      a great deal of publicity and concern with resulting national and international
      attempts at controlling the major serotypes, S. Typhimurium and S. Enteritidis,
      at the breeder and layer level. Control is possible through rigorous hygiene and
      management procedures, but is not always economically viable. As a result,
      control by serological and bacteriological testing and slaughter may also not be
      feasible. Antibiotics have been used to reduce carriage but can cause problems of
      resistance and increased susceptibility. The use of growth promoting antibiotics
      can also increase susceptibility to infection. Other means of increasing the
      resistance of poultry to infection are therefore being sought. These include the
      use of intestinal flora preparations for competitive exclusion of Salmonella from
      newly hatched chicks. Killed and live vaccines are used, both with some success.
      However, the safety of some live vaccines is still uncertain.

PMID- 10935269
TI  - Campylobacter infection of commercial poultry.
AB  - Campylobacter jejuni, a widespread food-borne pathogen is responsible for
      enteritis in the populations of both industrialised and developing nations and is
      acquired by consumption of contaminated water, milk and food products.
      Contaminated poultry meat is regarded as an important source of
      campylobacteriosis, with both commercial broiler and turkey growing flocks
      infected at two to three weeks of age by direct and indirect horizontal exposure.
      Non-chlorinated water is regarded as a vehicle of infection, followed by rapid
      intraflock dissemination. Intensification in the poultry industry has contributed
      to the increased prevalence rates on carcasses associated with increased stocking
      density and mechanized processing which are inherent to the high efficiency
      dictated by a competitive market. Currently, pre- and post-harvest control
      measures may ameliorate the problem of Campylobacter infection in consumers.
      Refrigerated storage and transport of red meat and poultry, appropriate handling
      and food preparation, and thorough cooking reduce the possibility of food-borne
      infection. In view of the world-wide distribution of C. jejuni infection and the
      multiplicity of sources, including non-pasteurised milk and contaminated water,
      it is inappropriate to impose trade restrictions on poultry meat based on the
      detection of campylobacters.

PMID- 10935270
TI  - Avian chlamydiosis.
AB  - Avian chlamydiosis (AC) can be economically devastating to producers and a
      serious public health problem. Most infections in humans are due to exposure to
      psittacine birds and pigeons; however, outbreaks resulting in severe disease and
      even death do occur in abattoir workers following processing of infected flocks.
      The disease occurs primarily in turkeys and ducks, but can affect all types of
      poultry. In poultry, the disease varies from one producing high morbidity and
      mortality to one that is asymptomatic. Farm workers and abattoir workers are at
      risk following exposure to either extreme. Although outbreaks of AC have declined
      since the 1970s, some parts of the world are now experiencing a rise in
      incidence. Whether the initial decrease was due to changes in production methods
      or to the increased use of antibiotics is not known. The mechanism for
      introduction of the disease into a flock or area is poorly understood. Wild birds
      are often infected by the same strains as domestic flocks and are therefore
      thought to play a major role in introduction. Data also indicate that vertical
      transmission may occur. Persistently infected carrier birds are known to be a
      source of chlamydiosis in the pet bird industry, but have not been confirmed as a
      source of infection in poultry flocks.

PMID- 10935271
TI  - Fowl typhoid and pullorum disease.
AB  - Fowl typhoid (FT) and pullorum disease (PD) are septicaemic diseases, primarily
      of chickens and turkeys, caused by Gram negative bacteria, Salmonella Gallinarum
      and S. Pullorum, respectively. Clinical signs in chicks and poults include
      anorexia, diarrhoea, dehydration, weakness and high mortality. In mature fowl, FT
      and PD are manifested by decreased egg production, fertility, hatchability and
      anorexia, and increased mortality. Gross and microscopic lesions due to FT and PD
      in chicks and poults include hepatitis, splenitis, typhlitis, omphalitis,
      myocarditis, ventriculitis, pneumonia, synovitis, peritonitis and ophthalmitis.
      In mature fowl, lesions include oophoritis, salpingitis, orchitis, peritonitis
      and perihepatitis. Transovarian infection resulting in infection of the egg and
      subsequently the chick or poult is one of the most important modes of
      transmission of these two diseases. Salmonella Gallinarum and S. Pullorum can be
      isolated by use of selective and non-selective media. Salmonella Pullorum
      produces rapid decarboxylation of ornithine whereas S. Gallinarum does not, an
      important biochemical difference between the two bacteria. Both FT and PD can be
      detected serologically by use of a macroscopic tube agglutination test, rapid
      serum test, stained antigen whole blood test or microagglutination test. Both
      diseases can be controlled and eradicated by use of serological testing and
      elimination of positive birds. Vaccines may be used to control the disease and
      antibiotics for the treatment of FT and PD. Although FT and PD are widely
      distributed throughout the world, the diseases have been eradicated from
      commercial poultry in developed countries such as the United States of America,
      Canada and most countries of Western Europe. Both S. Gallinarum and S. Pullorum
      are highly adapted to the host species, and therefore are of little public health
      significance.

PMID- 10935272
TI  - Avian mycoplasmosis (Mycoplasma gallisepticum).
AB  - Mycoplasma gallisepticum is the most economically significant mycoplasma pathogen
      of poultry, and has a world-wide distribution. In common with other mycoplasmas,
      M. gallisepticum is minute in size with minimal genetic information and with a
      total lack of a bacterial cell wall. These properties are reflected in a high
      degree of interdependence between M. gallisepticum and the host animal, and in
      the fastidious nature of the organism in vitro. Strains of M. gallisepticum
      differ markedly with respect to important biological properties such as
      pathogenicity, infectivity, tissue tropism and transmissibility. In addition,
      phenotypic variation of major surface antigens occurs at high frequency, which is
      a probable explanation for chronic infection by M. gallisepticum despite a strong
      immune response. Infection with M. gallisepticum has a wide variety of clinical
      manifestations, but even in the absence of overt clinical signs, the economic
      impact may be significant. The most dramatic disease presentation of M.
      gallisepticum is chronic respiratory disease in meat-type birds, often as one of
      several aetiological agents in a multi-factorial disease complex. Transmission of
      M. gallisepticum in ovo from infected breeder birds to progeny is the major route
      of dissemination of the infection, and is the prime consideration for
      international trade. In most countries, control programmes for M. gallisepticum
      are based on maintaining commercial breeding stock free of infection. In
      instances where control of M. gallisepticum infection is not feasible,
      vaccination, especially with newly developed live M. gallisepticum vaccines, is
      being evaluated as an option. Major advances in diagnostic methods have been made
      in recent years. Control programmes have been based on serological methods, with
      screening for infection usually accomplished by the slide plate agglutination
      (SPA) test or by enzyme-linked immunosorbent assay. Further serological testing
      and/or demonstration of the presence of the organism must be used to confirm SPA
      suspected positive tests. In principle, detection of the presence of the M.
      gallisepticum organism can be by isolation of the organism or detection of the
      deoxyribonucleic acid by molecular methods. Polymerase chain reaction represents
      a rapid and sensitive alternative to traditional culture methods, which require
      time-consuming specialised techniques. The development of molecular typing
      methods affords new opportunities for epidemiological studies and identification
      of reservoirs of infection.

PMID- 10935273
TI  - Newcastle disease and other avian paramyxoviruses.
AB  - Newcastle disease (ND), caused by avian paramyxovirus serotype 1 (APMV-1)
      viruses, is included in List A of the Office International des Epizooties.
      Historically, ND has been a devastating disease of poultry, and in many countries
      the disease remains one of the major problems affecting existing or developing
      poultry industries. Even in countries where ND may be considered to be
      controlled, an economic burden is still associated with vaccination and/or
      maintaining strict biosecurity measures. The variable nature of Newcastle disease
      virus strains in terms of virulence for poultry and the different
      susceptibilities of the different species of birds mean that for control and
      trade purposes, ND requires careful definition. Confirmatory diagnosis of ND
      requires the isolation and characterisation of the virus involved. Assessments of
      virulence conventionally require in vivo testing. However, in vitro genetic
      characterisation of viruses is being used increasingly now that the molecular
      basis of pathogenicity is more fully understood. Control of ND is by prevention
      of introduction and spread, good biosecurity practices and/or vaccination.
      Newcastle disease viruses may infect humans, usually causing transient
      conjunctivitis, but human-to-human spread has never been reported. Eight other
      serotypes of avian paramyxoviruses are recognised, namely: APMV-2 to APMV-9. Most
      of these serotypes appear to be present in natural reservoirs of specific feral
      avian species, although other host species are usually susceptible. Only APMV-2
      and APMV-3 viruses have made a significant disease and economic impact on poultry
      production. Both types of viruses cause respiratory disease and egg production
      losses which may be severe when exacerbated by other infections or environmental
      stresses. No reports exist of natural infections of chickens with APMV-3 viruses.

PMID- 10935274
TI  - Highly pathogenic avian influenza.
AB  - Highly pathogenic (HP) avian influenza (AI) (HPAI) is an extremely contagious,
      multi-organ systemic disease of poultry leading to high mortality, and caused by
      some H5 and H7 subtypes of type A influenza virus, family Orthomyxoviridae.
      However, most AI virus strains are mildly pathogenic (MP) and produce either
      subclinical infections or respiratory and/or reproductive diseases in a variety
      of domestic and wild bird species. Highly pathogenic avian influenza is a List A
      disease of the Office International des Epizooties, while MPAI is neither a List
      A nor List B disease. Eighteen outbreaks of HPAI have been documented since the
      identification of AI virus as the cause of fowl plague in 1955. Mildly pathogenic
      avian influenza viruses are maintained in wild aquatic bird reservoirs,
      occasionally crossing over to domestic poultry and causing outbreaks of mild
      disease. Highly pathogenic avian influenza viruses do not have a recognised wild
      bird reservoir, but can occasionally be isolated from wild birds during outbreaks
      in domestic poultry. Highly pathogenic avian influenza viruses have been
      documented to arise from MPAI viruses through mutations in the haemagglutinin
      surface protein. Prevention of exposure to the virus and eradication are the
      accepted methods for dealing with HPAI. Control programmes, which imply allowing
      a low incidence of infection, are not an acceptable method for managing HPAI, but
      have been used during some outbreaks of MPAI. The components of a strategy to
      deal with MPAI or HPAI include surveillance and diagnosis, biosecurity,
      education, quarantine and depopulation. Vaccination has been used in some control
      and eradication programmes for AI.

PMID- 10935275
TI  - Avian infectious laryngotracheitis.
AB  - Avian infectious laryngotracheitis (ILT) herpesvirus continues to cause sporadic
      cases of respiratory disease in chickens world-wide. Sources of transmission of
      ILT infection are three-fold, namely: chickens with acute upper respiratory tract
      disease, latently infected 'carrier' fowls which excrete infectious
      laryngotracheitis virus (ILTV) when stressed, and all fomites (inanimate articles
      as well as the personnel in contact with infected chickens). Infectious
      laryngotracheitis virus infectivity can persist for weeks to months in tracheal
      mucus or carcasses. Rigorous site biosecurity is therefore critical in ILT
      disease control. Furthermore, while current (modified live) ILT vaccines can
      offer good protection, the strains of ILTV used in vaccines can also produce
      latent infections, as well as ILT disease following bird-to-bird spread. The
      regional nature of reservoirs of ILTV-infected flocks will tend to interact
      unfavourably with widely varying ILT control practices in the poultry industry,
      so as to periodically result in sporadic and unexpected outbreaks of ILT in
      intensive poultry industry populations. Precautions for trade-related movements
      of chickens of all ages must therefore include an accurate knowledge of the ILT
      infection status, both of the donor and recipient flocks.

PMID- 10935276
TI  - Avian infectious bronchitis virus.
AB  - Infectious bronchitis virus (IBV) is prevalent in all countries with an intensive
      poultry industry, with the incidence of infection approaching 100% in most
      locations. Vaccination is only partially successful due to the continual
      emergence of antigenic variants. At many sites, multiple antigenic types are
      simultaneously present, requiring the application of multiple vaccines. Although
      many countries share some common antigenic types, IBV strains within a geographic
      region are unique and distinct, examples are Europe, the United States of America
      and Australia. Measures to restrict the introduction of exotic IBV strains should
      therefore be considered. Infectious bronchitis has a significant economic impact;
      in broilers, production losses are due to poor weight gains, condemnation at
      processing and mortality, whilst in laying birds, losses are due to suboptimal
      egg production and downgrading of eggs. Chickens and commercially reared
      pheasants are the only natural hosts for IBV. Other species are not considered as
      reservoirs of IBV. The majority of IBV strains cause tracheal lesions and
      respiratory disease with low mortality due to secondary bacterial infections,
      primarily in broilers. Nephropathogenic strains, in addition to tracheal lesions,
      also induce prominent kidney lesions with mortality of up to 25% in broilers.
      Strains of both pathotypes infect adult birds and affect egg production and egg
      quality to a variable degree. Infected chicks are the major source of virus in
      the environment. Contaminated equipment and material are a potential source for
      indirect transmission over large distances. Virus is present in considerable
      titres in tracheal mucus and in faeces in the acute and recovery phases of
      disease, respectively. Virus spreads horizontally by aerosol (inhalation) or
      ingestion of faeces or contaminated feed or water. The virus is highly
      infectious. Clinical signs will develop in contact chicks within 36 h and in
      nearby sheds within one to two days. Infection is resolved within fourteen days
      with a rise in antibody titres. In a small number of chicks, latent infection is
      established with subsequent erratic shedding of virus for a prolonged period of
      time via both faeces and aerosol. Movement of live birds should be considered as
      a potential source for the introduction of IBV. Isolation and identification of
      IBV is needed for positive diagnosis. The preferred method of isolation is to
      passage a sample in embryonating specified-pathogen-free chicken eggs.
      Identification is either by monoclonal antibody based enzyme-linked immunosorbent
      assay (ELISA) or polymerase chain reaction. Virus neutralisation test in tracheal
      organ culture is the best method for antigenic typing. Continual use of live
      vaccines complicates diagnosis since no simple diagnostic tool can differentiate
      a field from a vaccine strain. Nucleotide sequencing of the S1 glycoprotein is
      the only method to discriminate between all IBV strains. Serology is also
      complicated by continual use of live vaccines. For surveillance purposes, ELISA
      is the method of choice, regardless of the antigenic type of IBV involved. The
      assay is used to monitor the response to vaccination, but field challenge can
      only be detected if flock antibody status is monitored continually. The antigenic
      type of a challenge strain involved cannot be ascertained by ELISA.

PMID- 10935278
TI  - Infectious bursal disease (Gumboro disease).
AB  - Infectious bursal disease (IBD) (Gumboro disease) has been described throughout
      the world, and the socio-economic significance of the disease is considerable
      world-wide. Various forms of the disease have been described, but typing remains
      unclear, since antigenic and pathotypic criteria are used indiscriminately, and
      the true incidence of different types is difficult to determine. Moreover, the
      infection, when not fatal, leads to a degree of immunosuppression which is often
      difficult to measure. Finally, the control measures used are subject to
      variations, and seldom follow a specific or standardised plan. In the context of
      expanding international trade, the authors provide an overview of existing
      knowledge on the subject to enhance available information on the epidemiology of
      IBD, the identification of reliable viral markers for diagnosis, and the
      implementation of specific control measures to ensure a global and co-ordinated
      approach to the disease.

PMID- 10935279
TI  - Neoplastic diseases: Marek's disease, avian leukosis and reticuloendotheliosis.
AB  - The commercially important neoplastic diseases of poultry are Marek's disease,
      which is caused by a herpesvirus, and the avian leukoses and
      reticuloendotheliosis, which are caused by retroviruses. These diseases are
      responsible for economic loss due to both mortality and depressed performance.
      Marek's disease virus (MDV) and avian leukosis viruses (ALVs) are prevalent
      throughout the world, and new strains which arise in particular locations may
      spread across borders, thereby undermining national disease control measures.
      Reticuloendotheliosis virus (REV) is also present in many countries. Marek's
      disease virus is transmitted horizontally only, and international spread in
      hatching eggs and day-old chicks can be prevented by appropriate hygiene
      precautions. Transmission of ALV and REV occurs both horizontally and vertically
      (through the egg), and measures to prevent international spread are more
      demanding. Marek's disease is controlled by vaccination, whilst avian leukosis is
      controlled by virus eradication programmes, mainly at the primary breeding level.
      Similar virus control measures can be applied for reticuloendotheliosis if
      necessary. No strong evidence exists to suggest that these avian tumour viruses
      constitute a danger to public health.

PMID- 10935280
TI  - Poult enteritis complex.
AB  - Poult enteritis complex (PEC) is a general term that encompasses the infectious
      intestinal diseases of young turkeys. Some diseases, such as coronaviral
      enteritis and stunting syndrome, are relatively well characterised, while others,
      such as transmissible viral enteritis, poult growth depression and poult
      enteritis mortality syndrome, remain ill-defined. All forms of PEC are
      multifactorial, transmissible and infectious. Salient clinical features include
      stunting and poor feed utilisation that result from enteritis. In the more severe
      forms, runting, immune dysfunction and mortality are reported. Gross and
      microscopic lesions of enteritis are present in all forms but tend to be non
      specific. Other lesions may be present, depending on the agents involved. The
      basic pathogenesis involves the following: a) alteration of the intestinal
      mucosa, generally by one or more viruses infecting enterocytes; b) inflammation;
      c) proliferation of secondary agents, usually bacteria. Non-infectious factors
      interplay with infectious agents to modulate the course and severity of disease.
      Diarrhoea is believed to be primarily osmotic because of maldigestion and
      malabsorption, but may also have a secretory component. Transmission is primarily
      faecal-oral. No public health significance is recognised or suspected. Prevention
      is based on eliminating the infectious agents from contaminated premises and
      preventing introduction into flocks. This is accomplished by an effective
      cleaning, disinfection and biosecurity programme. All-in/all-out production or
      separate brooding and finishing units are helpful. Control may require regional
      co-ordination among all companies producing turkeys, especially if the production
      is highly concentrated, and a quarantine programme for more severe forms of PEC.
      No vaccines or specific measures for controlling the organisms involved in PEC
      are available. Treatment is supportive for the viral component, while
      antibiotics, especially those with efficacy against Gram positive bacteria, may
      help to reduce the impact to bacterial infections. Evidence suggests that PEC
      occurs wherever turkeys are raised commercially, but this is not well documented
      and distribution of the various organisms that have been associated with PEC is
      largely unknown. The disease causes enormous economic loss, mostly from failure
      of the turkey to reach its genetic potential.

PMID- 10935281
TI  - Avian adenoviruses.
AB  - Adenovirus infections are ubiquitous in commercially farmed birds, and probably
      in all avian species. There is a wide range of virulence, in some cases even
      within the same serotype. While many infections are subclinical and appear to be
      of little economic or welfare importance, significant outbreaks of disease
      associated with adenovirus do occur. These diseases are not of public health
      significance.

PMID- 10935282
TI  - Avian rhinotracheitis.
AB  - Turkey rhinotracheitis, now commonly termed avian pneumovirus (APV) infection, is
      associated with serious welfare and economic problems in susceptible populations
      of turkeys and probably also of chickens. The infection principally affects the
      upper respiratory tract, although egg-laying performance may also be affected in
      breeding turkeys. Secondary infections exacerbate the effects of the primary
      virus infection. The virus persists for only a short time both in the host and in
      the environment and is not known to be transmitted via the egg. Highly effective
      vaccines are available to control APV infections, and hence good biosecurity and
      careful use of these vaccines should enable infection to be controlled and spread
      restricted. Diagnosis and surveillance are normally performed serologically using
      enzyme-linked immunosorbent assays (ELISAs). Several different ELISA kits are
      available commercially, but these give variable results and are not wholly
      satisfactory since interpretation of results is difficult.

PMID- 10935283
TI  - Avian reovirus infections.
AB  - Avian reoviruses are ubiquitous among poultry flocks. Although infection is
      usually present without disease, reoviruses may occasionally be involved in
      several disease syndromes of which viral arthritis/tenosynovitis in chickens is
      the most important, particularly in broiler breeds. While reoviruses have been
      isolated from turkeys and several other species of birds with various conditions,
      the presence of the virus has been conclusively linked with disease in relatively
      few instances. In chickens in particular, avian reoviruses with a wide spectrum
      of pathogenic capability have been isolated and several antigenic types exist.
      Diagnosis is dependent on the detection of the virus in clinical samples,
      although the presence of the virus does not necessarily confirm that this is the
      cause of the disease, except where reoviruses are detected in affected joints.
      Serological tests are usually difficult to interpret in view of widespread and
      frequently harmless reovirus infection. The principal approach to control of
      viral arthritis/tenosynovitis is by vaccination using attenuated vaccines in
      young birds, followed by inactivated preparations for breeders intended to
      protect chicks by maternal antibodies. Many vaccines are based on the S1133
      strain isolated in the United States of America, but these may not be effective
      against antigenic variants.

PMID- 10935284
TI  - Fowl cholera.
AB  - Pasteurella multocida subspecies multocida is the most common cause of fowl
      cholera, although P. multocida subspecies septica and gallicida may also cause
      fowl cholera-like disease to some extent. However, the virulence properties of
      the different subspecies for various hosts have not been elucidated. The severity
      and incidence of P. multocida infections may vary considerably depending on
      several factors associated with the host (including species and age of infected
      birds), the environment and the bacterial strain. No single virulence factor has
      been associated with the observed variation in virulence among strains. Possible
      virulence factors include the following: the capsule, endotoxin, outer membrane
      proteins, iron binding systems, heat shock proteins, neuraminidase production and
      antibody cleaving enzymes. No RTX toxins (repeats in toxin) appear to be produced
      by P. multocida, but P. multocida exotoxin (PMT) could contribute to virulence in
      some avian infections. The epidemiology of fowl cholera appears complex.
      Traditional serotyping systems are only of limited use in epidemiological
      studies. In recent years, molecular typing methods have been applied to avian
      strains of P. multocida of different origin. The results obtained using these
      newer methods indicate that wild birds may be a source of infection to commercial
      poultry. Documentation suggesting that mammals play a similar role is not as
      comprehensive, but the possibility cannot be excluded. Carrier birds seem to play
      a major role in the transmission of cholera. Surviving birds from diseased flocks
      appear to represent a risk, but more recent investigations indicate that carriers
      of P. multocida may exist within poultry flocks with no history of previous
      outbreaks of fowl cholera. The significance of this awaits further investigation.
      The site of infection for P. multocida is generally believed to be the
      respiratory tract. The outcome of infections may range from peracute/acute
      infections to chronic infections. In the former type of infections, few clinical
      signs are observed before death and the lesions will be dominated by general
      septicaemic lesions. In chronic forms of P. multocida infections, suppurative
      lesions may be widely distributed, often involving the respiratory tract, the
      conjunctiva and adjacent tissues of the head. Diagnosis is always dependent upon
      isolation of the organism. For the detection of subclinical infections, mouse
      passage of relevant samples is recommended, but polymerase chain reaction and
      isolation attempts on selective media may represent alternatives. Confinement is
      probably the most effective way to prevent introduction of P. multocida. However,
      extensive management systems dominate in many parts of the world, and under such
      circumstances vaccination is recommended as a preventive measure. Unfortunately,
      the development of safe and efficient live vaccines still poses problems. As a
      result, control remains dependent on bacterins which exhibit significant
      disadvantages compared to live vaccines.

PMID- 10935285
TI  - Ostrich diseases.
AB  - Scientific knowledge of ostrich diseases is incomplete and very fragmented, with
      specific details on technical aspects of diagnostic and/or screening tests
      completely absent in most cases. Salmonella Typhimurium is common in multispecies
      collections and causes mortality in chicks younger than three months on
      commercial farms, but is rarely found in chicks older than six months, or
      slaughter birds of twelve to fourteen months in southern Africa. Campylobacter
      jejuni and Chlamydia psittaci are occasionally reported, mainly in young
      ostriches, but both remain a diagnostic challenge. Crimean-Congo haemorrhagic
      fever is transmitted to domestic animals including ostriches, principally by
      ticks of the genus Hyalomma. In the ostrich, the disease causes no clinical
      symptoms during a viraemia of approximately four days. Spongiform encephalopathy
      has not been reliably reported in ostriches, while anthrax has occurred rarely in
      modern times but was reportedly an important cause of death approximately 100
      years ago in South Africa. Salmonella Gallinarum and S. Pullorum are unknown in
      ostriches. Pasteurella multocida occurs but is easily contained with antibiotics.
      Mycoplasma spp. are regularly found in an upper respiratory disease syndrome
      complicated by opportunistic bacterial pathogens. Ostriches of all ages are
      susceptible to challenge by velogenic Newcastle disease virus (NDV), but standard
      inactivated La Sota poultry vaccines can stimulate protective immunity lasting
      over six months. The viraemic period in vaccinated slaughter ostriches is between
      nine and eleven days and there are no indications of a carrier state or presence
      of the virus in the meat or any other tissues after this period, with peak
      immunoglobulin G response reached on day fourteen post infection.
      Haemagglutination inhibition tests are significantly less sensitive and less
      specific than enzyme-linked immunosorbent assays. Cloacal and choanal swabs used
      for direct virological screening in clinically affected cases (field and
      experimental) could not detect NDV. All avian influenza isolates reported from
      ostriches have been non-pathogenic to poultry, even the H5 and H7 subtypes. Some
      of the latter have been associated with mortality of ostrich chicks in localised
      outbreaks during periods of inclement weather and with significant wild bird
      (waterfowl) contact. Borna disease causes a nervous syndrome in ostrich chicks,
      but to date, has only been reported in Israel. Eastern and Western equine
      encephalomyelitides cause fatal disease in ostriches and other ratites, with
      mortality ranging from less than 20% to over 80% in affected flocks. These
      diseases are present in North, Central and South America where the associated
      ornithophilic mosquito vectors occur. Equine and human vaccines are apparently
      safe and efficacious in ratites. Wesselsbron disease, infectious bursal disease
      (type 2), adenovirus and coronavirus infections have been reported from ostriches
      but the significance of these diseases is unclear. Due to the paucity of data
      regarding ostrich diseases and the unvalidated state of most poultry tests in
      this unique group of birds, strict observation of a pre-slaughter quarantine of
      thirty days is strongly advised, whilst live exports and fertile eggs should be
      screened through the additional use of sentinel chickens and/or young ostriches.

PMID- 10935286
TI  - Mekong malaria. Malaria, multi-drug resistance and economic development in the
      greater Mekong subregion of Southeast Asia.
AB  - This monograph brings together national malaria databases for 1996, 1997 and 1998
      from the 6 countries comprising the Greater Mekong Subregion of Southeast Asia:
      Cambodia, China (southern provinces), Lao People's Democratic Republic, Myanmar,
      Thailand, Viet Nam. The objective is to create a regional perspective in what is
      a global epicenter of drug resistant falciparum malaria, so to enhance the
      information flow required to improve malaria control on a regional basis in the
      context of economic and social change. Geographical Information Systems
      technology has been applied to the regional mapping of total reported malaria
      cases, malaria incidence, confirmed cases, parasite species distribution. There
      is great diversity in disease patterns in the 6 countries and at subnational
      administrative unit area level in each country, so that in the region as a whole
      there is marked asymmetry in disease distribution, with many areas of high
      endemicity. Focal expansion of maps in the vicinity of international border areas
      delineates the differential trans-border malaria distribution that presents a
      challenge for disease control. The malaria pattern is also depicted in
      environmental context against regional elevation and forest cover profiles, which
      affect mosquito breeding site distribution and agricultural activity. Data on
      resistance of falciparum malaria to a range of anti-malarial drugs summarise the
      historical and recent context of resistance development and spread in terms of
      geography and time frame. Data on population movement across international
      borders identify the magnitude of a major factor in the dispersal of malaria,
      including resistant parasite strains. Malaria control involves consideration of
      microeconomic capacity and operates in the broader context of macroeconomic
      policy: economic and social profiles of the region are included to provide this
      perspective. So too are maps depicting major economic development projects in the
      region, projects that have and will continue to have profound, dynamic impacts on
      malaria epidemiology. The geographic collation of regional malaria databases is
      thus placed in overall geographic, health, environmental and economic
      perspective. This beginning can form a basis for the development of an effective
      regional malaria surveillance system in the context of rapidly evolving social
      and infrastructural change, leading eventually to a multi-disease surveillance
      network.

PMID- 10935287
TI  - Univentricular atrioventricular connection: review of the current therapeutical
      possibilities.

PMID- 10935288
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 permanent 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- 10935290
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- 10935289
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 preestablished 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- 10935291
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- 10935292
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- 10935293
TI  - Lupus carditis.

PMID- 10935294
TI  - Transmission of infectious diseases through mouth-to-mouth ventilation: evidence
      based or emotion-based medicine?

PMID- 10935295
TI  - Poorly performed modified radical mastoidectomy.

PMID- 10935296
TI  - Acute laryngitis.

PMID- 10935297
TI  - Endoscopic view of the sites of origin of nasal polyps.

PMID- 10935298
TI  - A patient with endolymphatic hydrops refractory to shunt surgery.

PMID- 10935299
TI  - Cochlear otosclerosis.

PMID- 10935300
TI  - Facial nerve paralysis following repair of the external ear canal with ionomeric
      cement.
AB  - A 20-year-old man developed a complete facial nerve paralysis following surgical
      reconstruction of the posterior ear canal with ionomeric cement. The paralysis
      developed gradually during the second and third postoperative weeks. Six weeks
      following the complete removal of the cement, the facial nerve recovered
      completely. The literature contains reports of diffusion of aluminum ions, which
      can reach toxic levels in tissue fluid and adjacent bone as the cement hardens.
      This side effect has been reported to cause an inflammatory response in the dura
      and brain and has led to fatalities. To our knowledge, there has been no other
      report of an ionomeric cement having a direct toxic effect on peripheral nerve
      transmission. Because ionomeric cements are used routinely in otosurgery,
      especially in canal reconstructions where the proximity to the facial nerve is
      evident, it is important to use caution when introducing ionomeric cements into
      near-nerve anatomic locations.

PMID- 10935301
TI  - Cephalometric comparisons of craniofacial and upper airway structures in young
      children with obstructive sleep apnea syndrome.
AB  - We studied 15 children of preschool age who had obstructive sleep apnea syndrome
      to evaluate their dentofacial morphology in relation to the pharyngeal airway
      space. We found that (1) sleep apnea was often associated with mandibular
      retrognathia, (2) the lower incisors tended to exhibit a retrocline, (3) there
      were no significant differences in angular and linear measurements in the cranial
      base between patients with sleep apnea and a control group of 30 nonapneic
      children, and (4) the apneic children had a narrower epipharyngeal airway space
      than did the controls. These findings suggest that obstructive sleep apnea is
      probably caused by both adenoidal hypertrophy and abnormal development of the
      facial skeleton. We highly recommend cephalometric analysis as a valuable tool
      for conducting the presurgical evaluation of sleep apnea in children of preschool
      age.

PMID- 10935302
TI  - Positional vertigo as a first symptom of a cerebellopontine angle cholesteatoma:
      case report.
AB  - We report a case of a cerebellopontine angle cholesteatoma whose initial sign was
      benign paroxysmal positional vertigo (BPPV). Positional vertigo caused by a
      central pathology is extremely rare and is usually accompanied by other
      suspicious features. In this case, there were no additional neurotologic symptoms
      or signs. The only abnormalities were seen on Dix-Hallpike testing, but because
      they were not consistent with a diagnosis of BPPV, the decision was made to
      proceed to imaging. Diagnostic rigor is required when evaluating positional
      vertigo, as with all symptoms of imbalance, if such cases are not to be
      overlooked.

PMID- 10935303
TI  - Basal cell carcinoma metastatic to the parotid: report of a new case and review
      of the literature.
AB  - Basal cell carcinoma is the most common of the cutaneous malignancies, accounting
      for 65 to 75% of all skin cancers. The natural history of this disease is one of
      chronic local invasion. Metastatic basal cell carcinoma is a rare clinical
      entity, with a reported incidence of only 0.0028 to 0.5%. Approximately 85% of
      all metastatic basal cell carcinomas arise in the head and neck region. We
      present a case of basal cell carcinoma that spread to the parotid gland in a man
      who had multiple lesions on his scalp and face. We also review the literature on
      metastatic basal cell carcinoma of the head and neck, and we discuss its
      epidemiology, etiology, histopathology, and treatment.

PMID- 10935304
TI  - Nasal septal perforation: a rare extraintestinal manifestation of Crohn's
      disease.
AB  - Nasal manifestations of Crohn's disease are quite rare. They are typified by
      chronic mucosal inflammation, obstruction, bleeding, and occasionally septal
      perforation--signs and symptoms that are common to many disease states of the
      nose. Nasal findings, much like oral lesions, can precede the more typical
      gastroenterologic manifestations of Crohn's disease. Otolaryngologists should be
      aware of such an association and consider the diagnosis of Crohn's disease in
      atypical cases of nasal disease. We report the case of a 12-year-old boy who had
      severe Crohn's disease and a nasal septal perforation, and we discuss this
      complication in the context of its otolaryngologic manifestations.

PMID- 10935305
TI  - Fascioperiosteal flap and neo-osteogenesis in radical mastoidectomy: long-term
      results.
AB  - We performed an analysis of long-term outcomes data on 60 patients with chronic
      otitis media with cholesteatoma who had undergone a surgical procedure based on
      an improved radical mastoidectomy and an inferiorly based fascioperiosteal flap.
      We found that at the 2-, 7-, 10-, and 13-year postoperative followup visits, all
      mastoid cavities were healthy and reduced in volume. At the final examination,
      the mean cavity volume was found to be decreased by 39% of the mean volume
      measured 1 month postoperatively. This reduction in volume is attributable to the
      neo-osteogenic activity of the flap, which was confirmed by histopathologic and
      radiologic findings. No recurrences took place.

PMID- 10935306
TI  - [Estrogen replacement therapy in patients in remission after treatment for
      estrogen dependent cancer. Certainties are still lacking].

PMID- 10935307
TI  - [Specific modulators of estrogen action].
AB  - Selective estradiol receptor modulators (SERMs) are specific modulators of
      estradiol action. They are used in therapeutics to obtain an estrogenic effect on
      certain cells and an antiestrogenic effect on other cells. Recent progress in the
      knowledge of the mechanism of action of estradiols implies that new molecules
      could be designed. This progress involves the cloning of a new estradiol
      receptor, ER beta, the discovery of co-activators and the elucidation of their
      molecular mechanism of action, and the crystallization of the ligand binding
      domain in the presence of an agonist or an antagonist.

PMID- 10935308
TI  - [Biometry 2000. Fetal growth charts by the French College of fetal
      ultrasonography and the Inserm U 155].
AB  - OBJECTIVE: The aim of Biometry 2000 was to establish reliable sonographic fetal
      auxology reference charts for biparietal diameter, head circumference, abdominal
      diameter, abdominal circumference and femur length. DESIGN: A prospective
      multicentric longitudinal and transversal study was carried out. SUBJECTS: The
      data of this study were obtained from 35,456 scans recorded in 10,043 women for a
      period of one year. METHODS: Sonographic measurements were performed using a
      single method for each parameter. Twins and unknown gestational ages were not
      included. No exclusions were made for small-for-age, congenital malformations or
      any event during pregnancy. Assuming measurements have a normal distribution,
      centiles were calculated after polynomial regression models from mean and
      standard deviation according to gestational age in exact weeks from last
      menstrual period. RESULTS: A total of 32,584 fetal biparietal diameters, 20,400
      direct cephalic circumferences, 31,790 transverse abdominal diameters, 21,562
      direct abdominal circumferences and 30,960 femur lengths were obtained. Fetal
      growth charts with means, standard deviations and centiles are presented.
      CONCLUSION: The multicentric study, Biometry 2000, has established sonographic
      fetal charts derived from a large sample of scans and unselected pregnant women
      assuming a normal distribution.

PMID- 10935309
TI  - [Abdominal pregnancy and tubal pregnancy. Apropos of 1 case. An exceptional
      clinical event].
AB  - A case of non-progressive and earlier abdominal pregnancy, associated with an
      evolutionary tubal pregnancy is reported by the authors. This clinical situation
      is very rare, indeed, exceptional, because it concerns two successive and ectopic
      pregnancies. The poor obstetrical cover and the ineffectual supervision of the
      pregnancy explain in part these situations in our countries.

PMID- 10935310
TI  - [Characteristics of adolescent endometriosis: apropos of a series of 40 cases].
AB  - The particularities of endometriosis were analyzed based upon a series of 40
      cases of adolescents aged 11 to 19 years. It was possible to distinguish two
      entities: 1) endometriosis associated with an obstructive genital anomaly
      sometimes found in young patients, for which the severity depends upon the delay
      in establish the diagnosis; these lesions may regress spontaneously, sometimes
      completely, when the anomaly has been surgically treated; and 2) endometriosis of
      adolescents aged 17 years or older, noted mainly in the case of chronic pelvic
      pain or severe dysmenorrhea. Lesions are usually mild and are frequently
      atypical; they are potentially recurrent, but the possible consequences on
      subsequent fertility need to be studied further.

PMID- 10935312
TI  - [Contraception].

PMID- 10935311
TI  - [Role of endocervical curettage in the screening for cervical cancer: apropos of
      a series of 31 cases].
AB  - We present a study of 31 cases of pathologic cervical smear with an inconclusive
      colposcopy. The aim of this study was to compare the results of the cervical
      smear, colposcopy, cervical biopsy, endocervical curettage and conization. The
      endocervical curettage is a valuable complement to the colposcopy, especially in
      the case of an inconclusive colposcopy.

PMID- 10935313
TI  - [Bone densitometry].

PMID- 10935314
TI  - [Management of fibroma. Recommendations for clinical practice].

PMID- 10935315
TI  - [Should the regulations on voluntary interruption of pregnancy be relaxed in
      France?].

PMID- 10935316
TI  - Effect of iron on the survival of Vibrio cholerae in water.
AB  - Effect of iron in the form of ferric oxide (Fe2O3) on the survival of V. cholerae
      O1 was studied. V. cholerae O1 survived for 8 days in plain water whereas in
      presence of Fe2O3 it survived up to 15 days. Presence of organic material in the
      water further promoted the bacterial survival by at least 4 days. There was no
      difference between the behaviour of El Tor and classical biotype. These results
      indicate that the presence of iron in water could promote the survival of V.
      cholerae O1 in water and may play a significant role in the epidemiology of
      cholera.

PMID- 10935317
TI  - Prevalence of multidrug resistant organisms in an intensive care burn unit.
AB  - During January to December, 1998, analysis of an outbreak of infections in the
      burn intensive care unit (BICU) of the hospital attached to the Dayanand Medical
      College, Ludhiana was carried out. A total of 868 clinical samples from 290
      patients with more than 40 per cent thermal injury were investigated. These
      samples included 322 wound swabs, 325 blood and 221 urine samples. Bacterial
      pathogens were isolated from 80, 62 and 48 per cent samples of pus, blood and
      urine respectively. Among the nine different pathogens isolated, the more common
      were Pseudomona aeruginosa from pus, Staphylococcus aureus from blood and
      Escherichia coli from urine samples. Multidrug resistance was observed among
      these predominant pathogens. Identical drug susceptibility pattern was depicted
      by large number of isolates of Ps. aeruginosa, Staph. aureus, Esch. coli and
      Proteus mirabilis. Similar pathogens with identical drug sensitivity pattern were
      isolated from environmental samples of the BICU. The ongoing outbreak of hospital
      acquired infection (HAI) was significantly reduced after strictly adhering to the
      guidelines for control of HAI.

PMID- 10935318
TI  - Epidemiology of malaria outbreak (April/May, 1999) in Titabor Primary Health
      Centre, district Jorhat (Assam).
AB  - An investigation was undertaken of a malaria outbreak in the Primary Health
      Centre Titabor, district Jorhat, Assam during May/June 1999. The fever rate in
      the community since March 1999, was 44.4 per cent with an average case load of
      2.5 per family. The fever cases peaked in the third week of May. Slide positive
      and slide falciparum rates in mass blood survey, in the study village were 16.1
      and 14.5 per cent respectively with 90 per cent infection of Plasmodium
      falciparum. Males (SPR 17.5%) suffered relatively more than females (SPR 14.7%).
      Malaria prevalence was significantly less in individuals above 15 yr of age (SPR
      11.0%) as compared to those below 15 yr (SPR 22.9%). Prevalence of malaria as
      well as mosquito densities in different clusters of the village were inversely
      related to the distance from the forested Naga hills. Anopheles minimus and A.
      dirus were collected in good numbers with comparatively higher densities of the
      former. Several factors like unusual climatic conditions, inadequate
      surveillance, unsatisfactory laboratory services and inadequate indoor residual
      insecticide spray were instrumental for the outbreak.

PMID- 10935319
TI  - Superoxide anions mediate proliferative response in cardiac fibroblasts.
AB  - The study was undertaken to examine whether superoxide anions mediate a
      proliferative response in cardiac fibroblasts. Cardiac fibroblasts isolated from
      newborn Wistar rats were exposed to superoxide anion generating system
      (hypoxanthine + xanthine oxidase) and its effect on cell growth was assessed. A
      stimulatory response on fibroblast proliferation was observed. The proportion of
      proliferating cells increased within 3 h of treatment compared to the control and
      the cell density after 96 h of exposure remained significantly high (P < 0.0005).
      Inclusion of antioxidants neutralised the stimulatory response, fortifying the
      role of superoxide anions in cell proliferation. This observation indicates that
      superoxide anions can mediate a fibrotic reaction in the cardiac tissue.

PMID- 10935320
TI  - Cytogenetic studies of 1001 Down syndrome cases from Andhra Pradesh, India.
AB  - Cytogenetic data obtained from investigating 1001 patients of Down syndrome (DS)
      and their parents over a period of 20 years (January 1979-January 1999) are
      presented. The frequency of pure trisomy, mosaicism and translocation was 87.92,
      7.69 and 4.39 per cent respectively. The origin of the extra chromosome 21 due to
      meiotic non-disjunction was 79.24 per cent maternal and 20.76 per cent paternal.
      A high frequency of acrocentric chromosome associations was also observed in
      mothers of children of Down syndrome, this might have predisposed to an enhanced
      risk for non-disjunction. Birth order of DS showed a higher number of first and
      second borns. Reproductive performances of the parents indicated a high rate of
      abortions, compared to controls. Cytogenetic investigations carried out over
      these years greatly helped in the management of these children and for counseling
      the affected families.

PMID- 10935321
TI  - Total energy expenditure & physical activity level in chronically energy
      deficient Indian males measured by the doubly labelled water technique.
AB  - Total energy expenditure (TEE) and basal metabolic rate (BMR) in the free-living
      state were measured in healthy south Indians, by the doubly labelled water (DLW)
      method. From these measurements, estimates of physical activity level (PAL) could
      be calculated. A total of 18 subjects were studied in 3 groups of 6 subjects
      each: Group I (urban controls), Group II (urban slum, chronically undernourished)
      and Group III (rural). The urban slum recruits were chronically energy deficient
      (CED), and had a low BMI (average 17.0 kg/m2), while the rural subjects had an
      average BMI of 18.1 kg/m2. The TEE measured by the doubly labelled water
      technique was 11.2, 7.1 and 12.2 MJ/day for Groups I, II and III respectively.
      The TEE was significantly lower in the urban CED group as obtained by the one way
      ANOVA. The estimates of TEE by the DLW technique were compared with estimates
      made by whole body calorimetry, in the urban groups of subjects. The TEE obtained
      by calorimetry was 10.3 +/- 1.6 and 7.3 +/- 0.2 MJ/day in Groups I and II
      respectively. There were no significant differences between the TEE measured by
      the two methods, in both the groups. The two methods also correlated well, and
      the mean difference between the methods, in both groups was -0.5 +/- 1.1 MJ/day,
      which was about 6 per cent of the value of TEE measured by the DLW method. The
      calculated PAL (by using TEE measured by DLW/BMR) was 1.79, 1.54 and 1.90 for
      Groups I, II and III respectively. The results showed that the activity of
      chronically energy deficient subjects, in urban slums, was reduced, and that this
      may be their method of conserving energy to maintain a stable body weight. Rural
      males had a high activity level, even though they had a low BMI.

PMID- 10935322
TI  - Referrals for lung transplantation in Japan. Unique indications and necessity of
      living-donor lobar lung transplantation.
AB  - OBJECTIVES: The purpose of this study was to review all referrals to our lung
      transplant program and to find realistic options for accepted candidates in
      Japan. METHODS: During the period from April 1992 to August 1999, 45 referrals
      were received. After screening, 22 of the referred patients were admitted for an
      extensive inpatient evaluation, and 15 of these were accepted as candidates for
      transplantation. RESULTS: The indication was primary pulmonary hypertension in 9,
      bronchiectasis in 2, lymphangioleiomyomatosis in 2, idiopathic pulmonary fibrosis
      in 1, and pneumoconiosis in the other 1. Two of those with primary pulmonary
      hypertension went to the USA and there received bilateral lung transplant. One
      with bronchiectasis received living-donor lobar lung transplantation in our
      center. These three recipients are alive and doing well during the follow-up
      period of 11 to 69 months. Among the 12 patients who have not received lung
      transplant, 5 patients have died while waiting. CONCLUSIONS: Indications for lung
      transplant are quite distinct in Japan, and primary pulmonary hypertension is the
      most frequent indication. Living-donor lobar lung transplantation is a realistic
      option for properly selected candidates.

PMID- 10935323
TI  - Surgery in three-channeled aortic dissection. A 31-patient review.
AB  - OBJECTIVE: Three-channeled aortic dissection with 2 adjacent false lumens present
      is rare. METHODS: The 31 patients whose dissections we treated surgically
      accounted for 7.3% of the 426 patients with aortic dissection treated surgically
      between 1978 and May 1999. The 17 men and 14 women ranged in age from 24 to 77
      years (mean: 45 +/- 12 years). Marfan syndrome was present in 18. Pain was
      observed at different times in 20. computed tomography scanning and magnetic
      resonance image proved useful in preoperative diagnosis. The morphology of the
      1st and 2nd false lumens was Stanford type A + B in 13, type B + B in 15, type A
      + A in 2, and localized abdominal dissection in 1. RESULTS: Descending aortic
      replacement was done in 18 patients, thoracoabdominal aortic replacement in 7,
      ascending aortic replacement in 3, and others in 3. Five patients died in
      hospital and later during follow-up for 1-181 months (mean, 57 +/- 55 months).
      CONCLUSIONS: Pain recurring in patients with aortic dissection should alert the
      physician to the possibility of 3-channeled dissection and the necessity of
      surgery. The incidence of such dissection is high in patients with Marfan
      syndrome.

PMID- 10935324
TI  - Is diabetes mellitus a major risk factor in coronary artery bypass grafting? The
      influence of internal thoracic artery grafting on late survival in diabetic
      patients.
AB  - OBJECTIVE: The presence of diabetes could possibly have an adverse influence on
      the late results of coronary artery bypass grafting (CABG). A retrospective
      observational risk-unadjusted estimation study was conducted to clarify the
      magnitude of this unfavorable influence of diabetes based on our experience at
      Juntendo University. METHODS: Between January 1984 and December 1995, 1,618
      primary CABG operations were performed and 99.0% of these patients were followed
      up for a mean period of 81.2 months with a maximal follow-up of 14 years. Among
      the 1,610 patients who were successfully followed up, 523 patients (32.5%) were
      diabetic and this cohort was compared with 1,087 nondiabetic patients regarding
      the patient profiles, perioperative outcome, and the long-term outcome. RESULTS:
      Diabetic patients included a higher proportion of females, a greater preoperative
      presence of renal insufficiency, a higher rate of three vessel disease, and
      reception of a greater number of grafts (mean: 2.5 versus 2.4) and an internal
      thoracic artery graft (68% versus 58%). Hospital mortality was not significantly
      different (2.1% vs 1.0%: ns). An actuarial analysis revealed a significantly
      unfavorable long-term survival in the diabetic group (59.6%) at 14 years,
      compared with the nondiabetic group (73.4%), however diabetic patients with an
      internal thoracic artery graft had a favorable long-term survival (82.0%) at 13
      years, and this finding was almost identical to that of nondiabetic patients with
      an internal thoracic artery graft (88.5%). CONCLUSION: We conclude that the
      presence of diabetes appears to be a major risk factor in patients undergoing
      CABG. However, diabetic patients with an internal thoracic artery graft had a
      survival almost identical to that of nondiabetic patients with an internal
      thoracic artery graft.

PMID- 10935325
TI  - A staged Fontan approach in patients initially unsuitable for the primary Fontan
      procedure.
AB  - OBJECTIVE: To determine the efficacy of the Glenn procedure in terms of
      establishing the Fontan procedure. METHODS: Surgical results were investigated in
      248 patients undergoing either the total or partial right heart bypass. Of these,
      the conventional and the bidirectional Glenn procedures were employed in 27 and
      58 patients, respectively. RESULTS: Conversion to the Fontan circulation was
      attempted in 32 of 58 patients initially considered unsuitable for the Fontan
      circulation and undergoing the bidirectional Glenn procedure, with 2 operative
      deaths. Of the 27 undergoing the conventional Glenn procedure, 13 have undergone
      conversion with 2 deaths. Actuarial survival rate after the staged Fontan
      approach did not statistically differ from that after the primary Fontan
      procedure. Catheterization in 130 patients with the established Fontan
      circulation showed no significant differences in ejection fraction, end diastolic
      volume, and end diastolic pressure of the systemic ventricle, as well as in
      Cardiac Index, between the group of patients treated with the primary Fontan
      procedure and the group treated with the staged Fontan procedure. When achieving
      the bidirectional Glenn procedure, the size of the additional channel from the
      ventricles to the pulmonary arteries was correlated with the postoperative change
      in pulmonary arterial size, but such additional forward flow produced
      insufficient ventricular offloading in 9 of 16 patients with significant
      atrioventricular valvar regurgitation. CONCLUSION: The staged Fontan strategy has
      an advantage in patients with complicated circumstances. Whether the primary or
      the staged Fontan procedure was used, however, did not affect the Fontan
      circulation itself when once the Fontan circulation was established. The
      additional forward flow in the bidirectional Glenn physiology, if employed,
      should be appropriately adjusted, considering both the advantages and the
      disadvantages of the option.

PMID- 10935326
TI  - Extended septoplasty for subaortic stenosis developed 19 years after double
      outlet right ventricle repair.
AB  - A 27-year-old woman developed subaortic stenosis 19 years after double-outlet
      right ventricle repair. Subaortic stenosis was caused by a narrow ring of
      fibromuscular ridge associated with a bulge of the underlying septal muscle. The
      aortic valve was bicuspid and stenotic. We conducted extended septoplasty,
      replacing the aortic valve. Postoperative cineangiogram showed an adequate left
      ventricular outflow pathway. Double-outlet right ventricle repair may thus be
      followed by subaortic stenosis as long as 19 years after initial surgery. This
      lesion was assumed due to acquired disease secondary to flow disturbances in the
      left ventricular outflow, so reconstructing an adequate outflow pathway is
      effective and appears to help avoid recurring stenosis.

PMID- 10935327
TI  - Mitral valve replacement and subsequent composite graft replacement of the aortic
      root for infantile Marfan syndrome.
AB  - The cardiovascular lesions commonly seen in Marfan syndrome can frequently be the
      primary cause of premature death. Cardiac lesions involving both the mitral valve
      and the aortic root are commonly observed among patients diagnosed during early
      infancy, as so-called infantile Marfan syndrome. Since the lesions tend to
      progress rapidly with the end results of high morbidity and mortality, the
      majority of patients require surgical intervention at a young age. However,
      patients who undergo surgical intervention for both lesions during the first
      decade of life have been rarely reported in literature. In this report, we
      present a case of a 9-year-old boy who underwent aortic root replacement with a
      composite graft at 3.5 years after a prior prosthetic valve replacement of the
      mitral valve. Although the immediate result was satisfactory, the long-term
      result remains to be seen.

PMID- 10935328
TI  - Repair of partial anomalous pulmonary venous connection with a minimal atriotomy.
AB  - We present an alternative surgical technique for the repair of a partial
      anomalous pulmonary venous connection to the higher segment of the superior vena
      cava. Although the atriotomy is limited in this technique, a sufficiently large
      systemic venous chamber overlapping to the outside of the superior vena cava can
      be created.

PMID- 10935329
TI  - Aneurysms in the ascending aorta adherent to the sternum after cardiac surgery.
AB  - Sternotomy in a patient with an aneurysm in the ascending aorta adherent to the
      sternum after cardiac surgery can result in fatal hemorrhage or brain damage
      unless the distal ascending aorta can be identified and secured immediately. A
      left anterolateral thoracotomy was used in three patients with adherent
      aneurysms. The distal ascending aorta was isolated, and dissection was performed
      between the aneurysm and the sternum. There was no complication. This method was
      safe, and blood loss was minimized.

PMID- 10935330
TI  - Successful reoperation for diffuse supravalvular aortic stenosis.
AB  - We reoperated for diffuse supravalvular aortic stenosis using a modified
      technique of patch plasty described by Brom. A 36-year-old woman admitted to our
      hospital with a peak systolic pressure gradient of 92 mmHg across the ascending
      aorta had previously undergone Doty's operation at another hospital. Aortography
      showed an ascending aorta diffusely stenotic from the sinotubular junction to the
      aortic arch. We transected the ascending aorta just above the stenotic portion
      and incised the proximal wall to the sinus of Valsalva. Three patches were sewn
      to each sinus to expand them and the ascending aorta. The pressure gradient
      decreased postoperatively to 11 mmHg, and we conclude that this technique
      sufficiently relieves diffuse supravalvular aortic stenosis.

PMID- 10935331
TI  - Large pulmonary arteriovenous fistula.
AB  - A 55-year-old woman with Rendu-Osler-Weber disease underwent surgical resection
      of a pulmonary arteriovenous fistula deriving from right middle lobe vessels. The
      fistula was 10 x 6 x 5 cm, to our knowledge, the largest ever reported. Although
      the major part of the fistula was well exposed through median sternotomy,
      extensive bleeding during dissection of feeding and drainage vessels precluded
      safe dissection. Total cardiopulmonary bypass was therefore used to divert the
      pulmonary blood flow. Anatomy was clearly delineated and connecting vessels were
      safely suture-closed from within the fistula without sacrificing the right middle
      lobe vein, which might have been damaged without cardiopulmonary bypass. The
      postoperative course was uneventful, and no complications associated with
      cardiopulmonary bypass occurred.

PMID- 10935332
TI  - A rapidly growing benign intrathoracic neurofibroma after lung lobectomy.
AB  - A 67-year-old male underwent a right upper lung lobectomy for lung cancer in
      January 1993. Follow-up chest X-rays revealed a progressive and rapidly growing
      intrathoracic mass in the right thorax. The mass, however, did not resemble a
      tumor recurrence, and the patient complained only of shortness of breath.
      Computerized tomography and magnetic resonance imaging confirmed the presence of
      the intrathoracic mass and its associated compression of the residual lung. A
      right thoracotomy was performed in January 1998, and a mass found arising from
      the sympathetic nerve trunk was resected. Microscopic examination revealed
      stellate or spindle-shaped cells in myxoid stroma with sparsely distributed
      collagen fibers. Immunohistochemically, the cells were positive for neuron
      specific enolase, and the tumor was identified as neurofibroma. The patient did
      not suffer from von Recklinghausen's disease, and there was no family history of
      the disease. After resection of the neurofibroma, the compressed lung was able to
      re-expand, and the patient's shortness of breath disappeared. At one year
      postoperative, the patient remains well, and there is no evidence of recurrence.

PMID- 10935333
TI  - Primary repair of complete transposition of the great arteries with complete
      atrioventricular septal defect.
AB  - We successfully corrected complete transposition of the great arteries associated
      with complete atrioventricular septal defect in a 50-day-old infant in
      concomitant arterial switch operation and two-patch repair. The combination of
      these 2 complex anomalies is very rare, and primary anatomical repair is feasible
      in such patients.

PMID- 10935335
TI  - Rupture in a mitral papillary muscle following blunt chest trauma.
AB  - The successful surgical repair of an uncommon case of blunt chest trauma is
      described. A 28-year-old man was involved in a motorcycle accident during which
      the victim struck a pole at high speed. Extracorporeal membrane oxygenation was
      required with a tentative diagnosis of traumatic respiratory distress syndrome,
      but he nevertheless continued to show progressive deterioration. In the
      preoperative evaluation, transesophageal echocardiography clearly demonstrated an
      injury involving of mitral regurgitation secondary to total rupture of a
      papillary muscle. Mitral valve replacement was performed seven days after the
      accident. The importance of the diagnostic process and surgical treatment are
      emphasised.

PMID- 10935334
TI  - Mitral valve plasty in systemic lupus erythematosus in the setting of
      antiphospholipid syndrome.
AB  - The first case was of a 27-year-old female, who was diagnosed as having mitral
      valve stenosis with regurgitation, systemic lupus erythematosus and
      antiphospholipid syndrome at her previous pregnancy. We performed mitral valve
      plasty, which included open mitral commissurotomy and Kay's annulo plasty. The
      second case was of a 53-year-old female, who was diagnosed as old myocardial
      infarction, mitral regurgitation, systemic lupus erythematosus and
      antiphospholipid syndrome. She underwent mitral valve plasty and coronary artery
      bypass grafting. Both cases were treated by administration of methylpredonisolone
      and heparin perioperatively to avoid thrombosis and aggravation of systemic lupus
      erythematosus. Both patients showed good postoperative outcome without
      complications. We consider that it is important to perform the plasty as far as
      possible, and to administer effective anticoagulation treatment to prevent
      complications for patients in the setting of systemic lupus erythematosus and
      antiphospholipid syndrome.

PMID- 10935336
TI  - Simultaneous coronary artery bypass grafting and ascending aorta bifemoral bypass
      in small aorta syndrome.
AB  - A 55-year-old man with severe coronary artery disease and aortoiliac occlusive
      disease with small aorta syndrome was admitted to our department with angina
      pectoris and bilateral claudication. Intravenous subtraction angiography showed
      total occlusion of the right common iliac artery and 99% stenosis of the left
      common iliac artery with a markedly hypoplastic infrarenal aorta only 9 mm in
      diameter. It also revealed 90% stenosis at the origin of the left subclavian
      artery. Coronary angiography showed total occlusion of the left anterior
      descending artery and 90% stenosis of the circumflex artery. Simultaneous
      coronary artery bypass grafting and an ascending aorta-bifemoral bypass were
      conducted using an in-situ right internal mammary artery graft, an autologous
      saphenous vein graft, and a Y-figured expanded polytetrafluoroethylene graft.
      Postoperative angiography showed grafts to the coronary and bifemoral arteries
      were patient. This combined procedure is useful for patients with coronary artery
      disease and aortoiliac occlusive disease, especially in those with small aorta
      syndrome.

PMID- 10935337
TI  - Thoracic and cardiovascular surgery in Japan during 1998. Annual report by the
      Japanese Association for Thoracic Surgery. Committee of Science.

PMID- 10935338
TI  - Late onset hyalinosis cutis et mucosae.
AB  - Two cases of non-familial, late onset (50 and 62-years-old) hyalinosis cutis et
      mucosae were studied and compared with classical early onset cases. Late onset
      cases showed essentially the same histological and ultrastructural features
      described for early onset cases. The late onset variety should be distinguished
      from other diseases; they resemble systemic amyloidosis and sometimes the adult
      form of colloid milium.

PMID- 10935339
TI  - Transplant of cultured autologous pure melanocytes after laser-abrasion for the
      treatment of segmental vitiligo.
AB  - Segmental vitiligo is a special type of vitiligo with unilateral distribution of
      lesions and has a stable course. Clinically, many patients with segmental
      vitiligo have unsatisfactory responses to topical corticosteroid or UV
      phototherapy. We have developed a technique for the isolation of melanocytes from
      a small specimen of normally pigmented skin obtained via a suction blister. The
      melanocytes can be proliferated in culture and then replanted onto laser-abrased
      vitiliginous areas. We used this procedure to treat 25 patients with segmental
      vitiligo that were refractory to medical therapy. The repigmented portion of the
      total treated area amounted to 95-100% in 21 patients and 65 to 94% in 4
      patients. The response rate to treatment was 100% in this study. No scarring or
      other side-effects developed. The results of this study demonstrate that this
      method is a valuable tool for the treatment of patients with segmental vitiligo.

PMID- 10935340
TI  - Common contact sensitizers in Delhi.
AB  - Seventy-five patients of both sexes with clinically suspected contact dermatitis
      were patch tested with the Indian Standard Series and indigenous antigens. The
      results were compared with the data from other centers. Most of these patients
      were young adults between 20 and 39 yrs old with the mean age of 36.63 +/- 5.6
      yrs. Their occupational profiles included household workers (17.33%), masons
      (10.66%), farmers (6.66%), factory workers (4%), medical personnel (4%), lab
      workers (2.66%), and miscellaneous (17.33%). Itching and burning were two of the
      most common complaints, and chronic dermatitis was the predominant morphologic
      pattern of the lesions observed. Frequent sites involved included the hands
      (40.83%), airborne type (22.44%), hands and feet (12.24%), feet (12.24%), face
      (10.2%), and neck (2.04%). Patch test analysis of these patients revealed that,
      out of 75 subjects tested, 49 (65.3%) reacted to one or more allergens.
      Parthenium (20%) is the most common contact sensitizer followed by potassium
      dichromate (16%), xanthium (13.33%), nickel sulphate (12%), chrysanthemum (8%),
      mercaptobenzothiazole, and garlic (6.66% each). These findings are in broad
      conformity with those in other reports. We concluded that the Indian Standard
      Series of antigens with the addition of a few more (such as garlic, onion and
      chlorheximide of local relevance) is suitable for detecting the allergens
      responsible for the contact dermatitis prevailing in this region.

PMID- 10935341
TI  - A case of acute graft-versus-host disease following autologous peripheral blood
      stem cell transplantation.
AB  - A 42-year-old woman developed severe erythema with exfoliative scaling on the
      bilateral palms and soles and erosive dermatitis on the axillae and groin eight
      days after an autologous peripheral blood stem cell transplantation for the
      treatment of non-Hodgkin's lymphoma. She also developed exanthema; however she
      did not show intestinal, hepatic, or renal involvement. The skin biopsy revealed
      characteristic apoptotic cell death of the epidermis with eosinophilic necrosis,
      and she was diagnosed with acute graft-versus-host disease (GVHD). The cutaneous
      lesions responded to topical corticosteroid treatments and improved within a
      month without systemic immunosuppressing therapies. The cutaneous GVH reaction
      did not recur. However, she was treated with an intermittent thrombocyte
      transfusion because of persistent thrombocytopenia. On day 130, she developed
      intestinal pneumonia and died due to respiratory dysfunction. Unlike an allo-bone
      marrow graft, GVHD after an autologous stem cell transplantation is not common.
      Even for an autologous transplantation, GVH may develop with less characteristic
      clinical manifestations.

PMID- 10935342
TI  - Salivary gland MALT lymphoma associated with Helicobacter pylori infection in a
      patient with Sjogren's Syndrome.
AB  - We report a case of salivary gland MALT lymphoma in Sjogren's syndrome associated
      with localized H. pylori infection. A 76-year-old woman had a history of
      bilateral cheek masses for two years. Histologically, the parotid glands were
      invaded by numerous centrocyte-like cells to form lymphoepithelial lesions. The
      tumor cells showed immunohistological differentiation into B cells. Southern
      blotting demonstrated immunoglobulin gene rearrangement. These results indicated
      that the tumors were MALT lymphoma. H. pylori, as assessed by the urease test
      (CLO test; BML Ltd., Tokyo, Japan), was positive in the tumor specimen. After
      wide local excision of the tumors followed by radio therapy and oral
      administration of antibiotics and proton pump inhibitor, no evidence of
      recurrence was found during the 24-months of follow up. H. pylori infection in
      the salivary gland is rare, although the source of infection and transmission of
      H. pylori organisms has been thought to be the oral cavity. We discussed the
      association between H. pylori infection and salivary gland MALT lymphoma. The
      microorganism may play a role as an additional antigenic stimulus for the
      development of salivary gland MALT lymphoma as well as for the development of
      gastric MALT lymphoma. This means that H. pylori can play a role in lymphoma
      progression as booster of B cell lymphoproliferation.

PMID- 10935343
TI  - Electron microscopic study of Langerhans cell histiocytosis.
AB  - Among the several forms of Langerhans cell histocytosis (LCH), Letterer-Siwe
      disease is the most acute disseminated multisystemic variant. The course of
      Letterer-Siwe disease is usually rapid and fatal. We report here a cases of
      Letterer-Siwe disease which showed a good response to chemotherapy. We also
      describe the unusual ultrastructural findings in the histiocyte-like cells in
      this case.

PMID- 10935344
TI  - A case of mycosis fungoides after CD30 positive anaplastic large cell lymphoma.
AB  - A 55-year-old woman presented with mycosis fungoides (MF) after the total
      excision of primary cutaneous CD30+ anaplastic large cell lymphoma (ALCL). In the
      specimens obtained from the nodule of CD30+ ALCL and the plaque lesion of MF, the
      same pattern of T-cell receptor gene rearragement was detected.

PMID- 10935346
TI  - Phakomatosis pigmentovascularis with Sturge-Weber syndrome: a case report.
AB  - We describe here a Turkish girl with pigmentovascularis type 2b, consisting of
      disseminated Mongolian-spot-like maculae and unilateral Sturge-Weber
      angiomatosis.

PMID- 10935345
TI  - Dermatitis herpetiformis and vitiligo: report of a case and review of the
      literature.
AB  - We describe the case of a 53-year-old woman presenting papulous and
      papulovesicular lesions that were highly pruritic, localized mostly in the
      achromic areas of vitiligo and symmetrically distributed on the elbows, the
      buttocks, the shoulders and the neck. The histopathological examination performed
      on the elbow's lesional skin showed the presence of neutrophils and fibrin
      microabscesses at the tips of dermal papillae, with a few eosinophils, and small
      separations between the dermis and epidermis just over the infiltrate. The
      overlying epidermis was uninjured. The performed tests detected IgA anti
      endomysium, anti-thyrogloblin, anti-smooth muscle and anti-microsomal fraction
      autoantibodies; DIF showed the presence of IgA granular deposits at the dermo
      epidermal junction, prevalently at the tips of dermal papillae. This is the tenth
      case reported of an association between dermatitis herpetiformis and vitiligo.
      Although the two disorders both have immunological pathogeneses, we think that
      the topographic coexistence of both disorders is coincidental.

PMID- 10935347
TI  - Carcinoma erysipelatoides originating from stomach adenocarcinoma.
AB  - Carcinoma erysipelatoides is an uncommon form of cutaneous metastasis, which is
      most commonly caused by breast carcinoma, it has rarely been linked to the
      primary cancers of other organs. We report a 36-year-old woman with carcinoma
      erysipelatoides originating from a gastric carcinoma. Immunohistochemical and
      morphologic studies of skin biopsies revealed that the signet ring cells in the
      dilated lymphatics originated from adenocarcinoma of the stomach.

PMID- 10935348
TI  - A case of acrodermatitis enteropathica.
AB  - Acrodermatitis enteropathica is a rare hereditary disorder affecting zinc
      metabolism that is characterized by dermatitis, alopecia, gastrointestinal
      disturbances, eye infections, and growth failure. We report a 17-month-old girl
      with acrodermatitis enteropathica. Physical examination showed a cutaneous
      eruption consisting of vesiculobullous and psoriasiform skin lesions
      symmetrically distributed in the perioral, acral, and perineal areas. Her plasma
      zinc level was decreased (75 micrograms/dl), but within the normal range (60.00
      135.00 micrograms/dl). The patient was given zinc sulfate 50 mg/day. At the end
      of two months, she had significantly improved.

PMID- 10935349
TI  - Treatment of pyoderma gangrenosum with oral Tripterygium wilfordii
      multiglycoside.
AB  - Two patients with refractory pyoderma gangrenosum (PG) were treated with oral
      Tripterygium wilfordii multiglycoside (TWG). TWG is a Chinese medicine extracted
      from a medicinal herb, Tripterygium wilfordii Hook F, and has potent anti
      inflammatory and immunosuppressive effects. The effect of TWG on PG was
      demonstrated by clinical findings. Improvement of the lesions occurred within two
      weeks, and the ulcers healed about a month. Mild side effects such as
      gastrointestinal disturbances were observed in both patients. These side effects
      were patient-acceptable, and there was no need to stop the treatment. Transient
      elevation of serum ALT was observed in one patient; the serum ALT returned
      completely to normal after the discontinuation of TWG. These results suggest that
      TWG may be an effective alternative for refractory PG and that careful monitoring
      of liver function during TWG treatment is necessary.

PMID- 10935350
TI  - Topical anthralin for psoriasis vulgaris: evaluation of 70 Japanese patients.
AB  - In order to determine the usefulness of anthralin in the treatment of psoriasis,
      we evaluated the effectiveness of topical anthralin therapy in patients with
      psoriasis vulgaris in our hospital. Seventy patients with plaque-type psoriasis
      (58 men and 12 women), aged 17-79 years-old (mean; 47.6 years-old), who were
      treated at the Department of Dermatology, Tokyo Medical and Dental University,
      between 1992 and 1999, were retrospectively evaluated. Mean psoriasis activity
      and severity index (PASI) score before therapy was 24.6. Patients were treated
      with 0.1-2.0% topical anthralin. Responses were determined by clinical
      examination. The mean PASI score decreased to 8.7 after three months. The most
      effective anthralin concentration was 0.4-0.5%. The overall response rate was
      85.7%, complete remission was obtained in 21.4%, and partial remission in 64.3%.
      Ten patients (14.3%) were anthralin-resistant. In all patients who entered
      complete remission, recurrence was noted within six months after stopping
      anthralin. Minor skin irritation and pigmentation occurred in most of the
      patients; however, no severe side effects were noted during the treatment. Our
      study indicated that anthralin is effective for chronic plaque-type psoriasis.

PMID- 10935351
TI  - Scleroderma en coup de sabre with central nervous system involvement.
AB  - We describe a patient with scleroderma en coup de sabre and central nervous
      system symptoms. She presented with a linear scleroderma on her left paramedian
      forehead and scalp and suffered from headaches and dizziness. Axial T2-weighted
      MRI showed a 1 cm, high intense signal abnormality in the medial aspect of the
      left frontal lobe.

PMID- 10935352
TI  - Thoughtful screening.

PMID- 10935353
TI  - Cost-effectiveness analysis and screening tests for women.
AB  - Cost-effectiveness analysis is a method for identifying those medical
      interventions that are most effective given the resources available. This
      commentary focuses on the cost effectiveness of screening tests, with particular
      emphasis on such factors as the frequency and accuracy of the test; the risk of
      the condition and of adverse effects; the costs of screening, follow-up, and
      treatment; and the target population. The same test can be much more or less
      costly per year of life saved, and thus a better or worse use of medical
      resources, depending on how it is used. Results from cost-effectiveness analyses
      of a variety of screening interventions important to women (screening for
      cervical cancer and breast cancer, heart disease, diabetes, and mild thyroid
      failure) highlight the importance of developing screening protocols wisely so
      that women will receive the greatest possible benefit from their use.

PMID- 10935354
TI  - Breast and cervical cancer screening for older women: recommendations and
      challenges for the 21st century.
AB  - The incidence of both breast and cervical cancer increases with age, and older
      socioeconomically disadvantaged and minority women are most likely to develop or
      die of these diseases. Early detection has the potential to decrease the
      disproportionate burden of disease in these vulnerable groups at a reasonable
      cost to society. Yet despite impressive overall gains in use of mammography and
      Pap smears, older women, especially older minority women, remain underrepresented
      in screening programs. Physician recommendation is one of the most powerful
      predictors of screening across all age, socioeconomic, and ethnic groups. The
      overwhelming majority of older women, make one or more physician visits each
      year, each of which represents an opportunity to screen for breast and cervical
      cancer. Although older women will accept screening if it is offered by their
      providers, physicians are less likely to offer it to them than to their younger,
      white patients. Conflicting professional recommendations for screening older
      women, leaving older women out of clinical trials of screening efficacy,
      competing causes of mortality with increasing age, and possible negative
      attitudes held by physicians and patients all contribute to the underscreening of
      older women. Cancer control challenges for the next century include defining
      groups of women most likely to benefit from screening (based on age, disease
      risk, competing mortality, and quality of life), improving regular use of early
      detection, educating providers, and conducting research on age-mediated
      differences in breast or cervical cancer biology that could affect screening
      recommendations.

PMID- 10935355
TI  - Human papillomavirus screening and cervical cancer prevention.
AB  - Infection with one of several types of human papillomavirus (HPV) appears to be a
      necessary first step in the development of invasive cervical cancer. We cannot
      currently treat HPV infections; thus, the role of HPV testing is to identify
      women with precancerous lesions that can be removed and, in so doing, prevent
      progression to invasive carcinoma. Although HPV testing may help to identify
      women at risk of cervical cancer who might be missed by other screening tests, it
      is inherently nonspecific at identifying those who would otherwise develop
      cervical cancer. In order to avoid overtreatment of women with minor lesions with
      little potential for progression, HPV testing needs to be repeated or combined
      with Pap smears. Protocols for HPV screening have yet to be properly evaluated.
      Here we consider several possible applications of HPV testing in the prevention
      of cervical cancer. The most immediate role is as a secondary test in women with
      minor cytological abnormalities. Appropriate use of HPV testing as a primary
      screening tool depends on the setting. In a developed country without an
      organized screening program, HPV testing might be used in addition to Pap smears
      in women age 35 and over to increase sensitivity. Within an organized screening
      program, HPV testing might be used in combination with Pap testing, but with
      extended screening intervals so as to obtain the maximum advantage to women
      without unduly increasing costs. Where resources are strictly limited, an
      attractive option would be to perform visual inspection of the cervix after
      application of dilute acetic acid using a low threshold for referral, and to test
      for HPV only on those with abnormal looking lesions.

PMID- 10935356
TI  - Bacterial vaginosis: a public health problem for women.
AB  - Bacterial vaginosis (BV) remains a moderately prevalent condition with clearly
      observed links to adverse reproductive, gynecological, and other outcomes in
      women, including human immunodeficiency virus infection. Because of inconsistent
      findings from clinical studies concerning BV's etiologic role, no definitive
      policies with respect to screening and treatment have yet been established. Of
      concern is the high, unexplained prevalence of BV among African-American women,
      who are also at extremely high risk for preterm birth. The complexity of the
      sociodemographic picture challenges the field of public health to continue to
      explore the role of BV and its relationship to a whole host of social and
      biomedical conditions that may contribute to adverse health outcomes among
      society's most vulnerable members. Future decisions about screening and
      treatment, currently based on the biomedical model, may need to take into
      consideration issues of social context and expanded views of causality if we are
      to better understand and eliminate those factors that place individual women at
      risk of adverse outcomes, as well as the conditions that underlie racial and
      ethnic disparities in health.

PMID- 10935357
TI  - Reducing complications from alcohol use during pregnancy through screening.
AB  - Prenatal providers are reluctant to discuss alcohol use in the clinical setting,
      even though heavy alcohol use is associated with fetal alcohol syndrome (FAS) and
      fetal alcohol effects (FAE), sometimes known as alcohol-related
      neurodevelopmental disorder. Fourteen percent to 20% of pregnant women report
      drinking some alcohol during pregnancy. Approximately 0.2% to 1% meet the
      criteria for heavy drinking. Reducing drinking during pregnancy has the potential
      to reduce the risk for FAS and FAE. Routine screening for alcohol use during
      pregnancy followed by referrals for those considered to be at risk is
      recommended. Women are often more receptive to intervention during pregnancy, as
      they focus on positive health behaviors. A number of brief screening tools
      designed for use on a routine basis are reviewed. Physicians who learn to
      comfortably discuss alcohol use during pregnancy can help substantially reduce
      the impact of these disorders.

PMID- 10935358
TI  - Practical issues in bone mineral density testing.
AB  - Osteoporotic fractures are a source of morbidity and mortality among
      postmenopausal women. Clinicians must strive to identify women at risk for
      osteoporotic fracture and institute proper prophylactic or treatment regimens to
      decrease the incidence of fractures. The advent of more sensitive, less
      expensive, and portable bone mineral density assessment techniques, coupled with
      new strategies for identifying risk factors, has made it easier for clinicians to
      diagnose this debilitating disease before a fracture occurs. The hope is that
      bone mineral density testing will result in the early identification of women at
      risk for osteoporosis, thereby reducing the incidence of osteoporotic fractures.

PMID- 10935359
TI  - Lipid screening in women.
AB  - Evidence of the benefits of lowering cholesterol in various populations continues
      to grow, but questions persist about screening and treatment of lipid disorders
      in women. In this paper, we review the distinct features of the epidemiology of
      lipids and coronary heart disease in women and data from recent long-term
      treatment trials specific to women. Although data from primary prevention trials
      in women remain sparse, recent trials demonstrating benefits of cholesterol
      reduction across a broad range of cholesterol levels and cardiac risk in men and
      women bolster the conclusion that benefits may extend to asymptomatic women who
      are otherwise at high risk for coronary disease. Periodic lipid screening
      beginning in middle age will identify most women who are at high enough risk to
      merit drug therapy or more intensive individual lifestyle interventions. More
      detailed consideration of age, diabetes, blood pressure, specific lipid levels,
      or the ratio of total cholesterol to high-density lipoprotein cholesterol, and
      other risk factors can more accurately estimate individual risk of coronary heart
      disease and identify high-risk women most likely to benefit from lipid reduction.
      Advice about healthy diet, weight control, and physical activity can benefit all
      women, but authorities differ on the benefits of routine lipid screening in low
      risk younger women.

PMID- 10935360
TI  - Risks associated with genetic testing: health insurance discrimination or simply
      business as usual?
AB  - Doctors can test patients for mutations that put them at high risk for hereditary
      forms of such diseases as breast and ovarian cancer. Even though the
      opportunities for disease prevention using genetic testing will increase with
      time, the risks of testing, which include insurance loss and employment
      discrimination, currently make testing problematic. Some have proposed making use
      of genetic information in health insurance underwriting illegal. But in the
      current system of risk-based underwriting, it is hard to imagine that insurance
      companies will willingly forego access to a growing body of information on risk.
      If the American public chooses to limit the use of genetic information, a
      reassessment of current laws or methods of paying for health care will be needed.

PMID- 10935361
TI  - Coding abuse.

PMID- 10935362
TI  - Medical abortion.

PMID- 10935363
TI  - ECG of the month. Nowhere to go. Second-degree AV block.

PMID- 10935365
TI  - Radiology case of the month. Cerebrovascular accident. Mitochondrial
      encephalomyopathy.

PMID- 10935364
TI  - Tracheal stenosis.
AB  - While still an uncommon cause of airway obstruction, the incidence of tracheal
      stenosis in adults has increased with the use of assisted ventilation. The
      etiology, diagnosis, and treatment of tracheal stenosis are discussed. Special
      attention is paid to post-intubation tracheal stenosis and to tracheal resection
      as its most successful treatment option.

PMID- 10935366
TI  - The journal 150 & 100 years ago. June 1850 and 1900.

PMID- 10935367
TI  - Can we prevent type 1 diabetes?
AB  - Preliminary laboratory and clinical studies suggest that the clinical onset of
      type 1 diabetes can be delayed or prevented in high-risk individuals. The NIH
      sponsored Diabetes Prevention Trial Type 1 is currently underway to determine
      whether prevention is possible using insulin to alter the autoimmune process.

PMID- 10935368
TI  - Pathologic disruption of the distal biceps brachii tendon by synovial sarcoma.
AB  - This article illustrates the utility of musculoskeletal magnetic resonance
      imaging in providing contrast resolution of soft body tissues (i.e., biceps
      tendon) and pathologic processes (i.e., synovial sarcoma). The evaluation of
      biceps tendon injury and the diagnosis/staging of synovial sarcoma are best
      complemented by this most sensitive, non-invasive imaging method, particularly
      when combined as in this unique case.

PMID- 10935369
TI  - Hypertension treatment in the new millennium: the importance of controlling
      systolic blood pressure and the pulse pressure.
AB  - The sixth Joint National Committee on Hypertension (JNC-VI) has recently been
      published. The new criteria emphasize the importance of controlling systolic
      blood pressure and paying attention to the level of pulse pressure. The authors
      believe in the importance of controlling both in compliance with the new criteria
      established by JNC-VI.

PMID- 10935370
TI  - Pathobiological determinants of atherosclerosis in youth (PDAY) cardiovascular
      specimen and data library.
AB  - In 1985, investigators organized a multi-center study, Pathobiological
      Determinants of Atherosclerosis in Youth (PDAY), to examine the relationships of
      cardiovascular risk factors to atherosclerosis involving more than 3,000 young
      persons 15 through 34 years of age who died of external causes. Reports from the
      PDAY group confirmed that atherosclerosis begins in the teens and showed that the
      progression of the lesions is strongly influenced by the same risk factors that
      predict risk of clinically manifest coronary disease in middle-aged adults. The
      results emphasize the need for early and aggressive control of all risk factors
      in young persons for long-range prevention of coronary heart disease and related
      diseases. Recent funding by the Louisiana Cancer and Lung Trust Fund (LCLTF) has
      assisted Pathology at Louisiana State University Health Sciences Center (LSUHSC)
      in the following objectives: (1) maintaining this national research resources;
      (2) making the unique specimens available to interested investigators; and (3)
      continuing support for studies at LSUHSC which investigate the effects of smoking
      on the development of atherosclerotic lesions.

PMID- 10935371
TI  - [Combined CABG and valve operation].
AB  - We presented 20 patients, who were underwent combined valve and coronary artery
      bypass surgery in our institute from September 1995 to December 1999. They were
      13 male and 7 female, ages ranged from 54 to 79 (mean 67.5 years). Previous
      cardiac operation was done in 2 cases. The patients carried out a combination of
      CABG with aortic valve replacement (n = 9), mitral valve replacement (n = 4),
      mitral valve plasty (n = 6), double valve replacement (n = 1). Emergency
      operation was performed in 2 cases. The hospital mortality was 5%. One patient
      who was underwent mitral valve repair and CABG died due to severe heart failure 2
      week post operatively. The perioperative complications were found in 2 patients,
      one was acute renal failure with HD, the other was cerebral infarction. There are
      no patient with perioperative myocardial infarction. The combined operation of
      valvular surgery and CABG for the patients with coexisting disease might be
      safety and reliable methods, even in older one.

PMID- 10935372
TI  - [Management of coronary artery disease combined with aortic stenosis: how to do
      with mild aortic stenosis].
AB  - A total of fourteen patients with combined operation of coronary artery bypass
      grafting (CABG) and aortic valve replacement (AVR) for coronary artery disease
      (CAD) and aortic stenosis (AS) were reviewed to evaluate the indication of the
      combined operation. Preoperative pressure gradient across the valve and effective
      orifice area were 21-89 mmHg (mean 64 mmHg), 0.5-1.9 cm2 (mean 0.92 cm2),
      respectively. The extent of CAD was 1-3 (mean 2.0). Fractional shortening (%FS)
      ranged from 13% to 43% with mean value of 28%. All patients underwent CABG and
      AVR. The number of grafts was 1-4 (mean 2.3) with internal thoracic artery used
      in 7 cases. Mechanical valves were employed for all patients except 1 case with
      cerebral aneurysm. There was no operative death, although low output syndrome
      developed in 2 cases. One had poor left ventricular function preoperatively, and
      the other was emergency case. Fractional shortening improved postoperatively even
      in two cases with preoperative %FS less than 20%, and all grafts were patent on
      postoperative coronary angiography. The event-free survival was 100% during 32
      months of mean follow-up. Combined AVR with CABG is recommended to avoid risky
      secondary operation in patients of CAD and AS, even if one of which is relatively
      mild, because of the fact that operative and late results of the combined surgery
      are satisfactory.

PMID- 10935373
TI  - [Retrograde continuous cold blood cardioplegia for combined aortic valve
      replacement and coronary artery bypass grafting].
AB  - Efficacy of retrograde continuous cold blood cardioplegia (RCBC) during aortic
      valve replacement combined with coronary bypass grafting was studied. Forty
      patients underwent elective aortic valve replacement, either combined with
      coronary bypass grafting (7 patients: group I), or isolated (33 patients: group
      II) using RCBC between 1996 and 1999 were analyzed retrospectively. Aortic cross
      clamp time was significantly prolonged in group I (150 +/- 33 min) compared to
      group II (109 +/- 32 min). The postoperative peak creatine kinase-MB levels were
      similar in both groups (73.3 +/- 23.9 versus 97.6 +/- 88.7 ng/ml). The doses of
      dopamine and dobutamine administered during 24 hours after surgery did not differ
      between the two groups (7.5 +/- 3.9 versus 6.5 +/- 5.5 mg/kg). The early (< 30
      day) mortality was 0 in group I, and 3.0% in group II. These results suggest that
      RCBC is a safe method of myocardial protection in patients undergoing aortic
      valve replacement combined with coronary artery bypass grafting.

PMID- 10935374
TI  - [Effectiveness of retrograde tepid blood cardioplegia in valve surgery combined
      with coronary artery bypass grafting].
AB  - The purpose of this study was to evaluate the usefulness of continuous retrograde
      continuous tepid blood cardioplegia (CTBC) in 8 patients underwent multivalve
      surgery combined with coronary artery bypass grafting (CABG) (Group 1), in
      comparison with antegrade CTBC in 10 patients with single valve replacement
      (Group 2). Aortic crossclamp time in Group 1 (187.9 +/- 55.2 minutes) was
      significantly longer than that (94.1 +/- 27.4) in Group 2 (p < 0.005). There was
      no hospital death in both groups. Spontaneous recovery rate of the heart beat
      following aortic declamping was 75% in Group 1, 90% in Group 2 (ns).
      Postoperative max CK-MB was 87.9 +/- 43.1 IU/l in Group 1, 74.8 +/- 27.0 IU/l in
      Group 2 (ns). During the early postoperative period, LVSWI significantly
      increased in both groups, whereas RVSWI showed no significant increase in both
      groups. Accordingly, in Group 1 in spite of longer aortic crossclamp time
      comparing Group 2, myocardial protection was considered to be satisfactory. In
      conclusion, retrograde CTBC is useful as an intraoperative myocardial protection
      in multivalve surgery combined with CABG which must need much longer aortic cross
      clamp time.

PMID- 10935376
TI  - [Clinical evaluation of cardiac valve surgery combined with coronary artery
      bypass grafting].
AB  - Between 1991 and 1999, 23 cases underwent cardiac valve surgery concomitant with
      myocardial revascularization at our institution. Twelve cases (group I) had a
      primary valvular disease combined with coronary atherosclerosis, and other 11
      cases (group II) were due to ischemic mitral insufficiency. There were 2 hospital
      deaths in group I (17%) and 4 in group II (36%). Three deaths in group II
      underwent left ventricular volume reduction surgery. On the basis of this
      observation, we concluded severe mitral regurgitation with ischemic
      cardiomyopathy was a particularly difficult management problem with disappointing
      clinical results. On the other hands, we considered concomitant revascularization
      should be done in the case of primary valvular disease when angiographically
      significant coronary artery stenosis was present.

PMID- 10935375
TI  - [Combined valvular and coronary artery surgery].
AB  - Between 1990 and 1999, 78 patients underwent combined valvular coronary artery
      operation. Aortic valve disease was present in 49 patients, mitral valve disease
      in 23 patients, aortic and mitral valve disease in 6 patients. The average age
      was 67 years. Twelve patients had had a previous myocardial infarction. The
      average number of grafts inserted was 1.82 per patients, and the average number
      of artery grafts inserted was 0.96 per patients. The most number of grafts were
      placed prior to valve replacement or plasty. And periods of myocardial ischemia
      were kept at a minimum by coronary perfusion through free grafts. Preoperative
      mortality was 1.3%. And event fee ratio after operation was 95% (mean follow up
      42 month). Therefore the operative risk of combined surgery is, in general, low
      and the long term results are favorable.

PMID- 10935377
TI  - [Combined valve and coronary artery bypass surgery].
AB  - Between January 1997 and November 1999, 31 patients underwent combined valve and
      coronary artery bypass grafting (CABG) surgery in our institute. There was no
      hospital death and clinical symptom improved in all patients after surgery. Mean
      follow-up was 16.3 months. The actuarial survival rate was 96.8% at 1 year. There
      were 4 late deaths (CHF in 3, arrhythmia in 1). Tepid blood cardioplegia was
      effective for those operations. Operation of CABG combined with valve surgery or
      LV surgery could be safely performed. We therefore considered that complete
      correction of the lesion with not only CABG but also combined valve surgery or LV
      surgery was the procedures of choice in patients with complicated lesions.

PMID- 10935378
TI  - [Surgical results of valvular heart disease combined with myocardial
      revascularization].
AB  - Risk factors for hospital death after combined valvular and coronary artery
      bypass surgery were examined in 131 consecutive cases between October 1988 and
      December 1999. These accounted for 8.0% of all 1,644 cases of coronary
      revascularization surgery and 15.3% of all 854 cases of valvular heart disease
      surgery. 84 men and 43 women underwent combined valvular and coronary artery
      bypass surgery. The mean age of the patients was 68.9 +/- 3.9 (22-86) years old.
      Numbers of cases comprised 58 undergoing aortic valve surgery, 63 undergoing
      mitral valve surgery, and 10 undergoing eight patients died during
      hospitalization after the operation: four due to cardiac death and four due to
      non-cardiac death. We studied pre- and perioperative risk factors for hospital
      death by means of multivariate analysis. As the major factors, ischemic mitral
      regurgitation, chronic renal failure, and duration of cardiopulmonary bypass were
      identified as three major predictors of hospital death. Ischemic mitral
      regurgitation was the strong predictor (p = 0.03) with 5 hospital deaths out of
      38 ischemic mitral regurgitation cases (13.1%), whereas only 3 hospital deaths
      were seen in 93 other cases (3.2%) operated on in the same period. Over all
      operation results were not unfavorable, indicating that combined operations may
      be electively performed if severe coronary artery disease was present. The
      surgical results with ischemic mitral regurgitation are as yet not well
      documented and will require further study.

PMID- 10935379
TI  - [Results of valve surgery combined with CABG].
AB  - During recent 8 years, combined procedures of valve surgery and coronary artery
      bypass grafting (CABG) were performed in fifty-five patients at Omiya Medical
      Center. AVR (31 cases), MVR (12 cases), MVP (8 cases), DVR (1 case), TVR (1
      case), TAP (2 cases) were performed with the average of 2.0 bypass graftings in
      this series. Five patients died due to organ ischemia (3 cases), cerebral
      embolism and heart failure. Organ ischemia occurred in dialysis patients and the
      results of combined surgery in dialysis patients were unsatisfactory (3/5 cases,
      mortality rate is 60%). On the other hand, the results of combined surgery in non
      dialysis patient is reasonable (2/50 cases, mortality rate is 4%). Before the
      combined surgery in dialysis patient, careful analysis of surgical risk including
      organ ischemia is needed and avoiding the prolonged perfusion time is important
      to achieve a successful surgical result.

PMID- 10935380
TI  - [Management strategy for patients with coronary artery disease associated with
      valve disease].
AB  - BACKGROUND: The indication of combined operation of coronary artery bypass (CAB)
      and valve surgery is controversial. METHODS: Between April 1992 and January 2000,
      13 patients underwent a combined operation with CAB and valve replacement, and 4
      patients (2 were overlapped) who had had a previous CAB underwent a reoperative
      valve replacement. RESULTS: One patient who underwent AVR and reCAB 11 years
      after the initial CAB died. Another patient with preoperative MRSA pneumonia and
      received MVR and CAB died 4 months after surgery with MRSA sepsis. However,
      others showed an excellent post-operative course. The causes of necessitating the
      reoperation were: unawareness of aortic stenosis at the initial emergency CAB in
      1 patient, progression of aortic stenosis in 1 patient, progression of aortic
      regurgitation in 1 patient, and progression of mitral regurgitation in 1 patient.
      CONCLUSION: The results of the combined CAB and valve replacement operation were
      acceptable. Patients with mild-moderate valve disease should be considered as
      candidates for valve surgery at the time of CAB.

PMID- 10935381
TI  - [Concomitant surgical treatment of valvular heart disease and coronary artery
      disease].
AB  - Concomitant valvular surgery and coronary artery bypass grafting were performed
      in 24 patients. Aortic valve replacement was carried out in 18 cases (A group),
      and mitral valve surgery (M group) was done in 6 cases (replacement in 3, and
      plasty in 3). There were two hospital deaths (11.1%) in the A group, and two
      (33.3%) in the M group of mitral valve replacement with Hancock II. One late
      death was observed in the M group. Aortic valve replacement with coronary
      revascularization resulted in satisfactory outcome. However, surgical management
      of concomitant mitral valve and coronary artery disease may need to be improved.

PMID- 10935382
TI  - [Combined operation for ischemic heart diseases and valvular heart diseases].
AB  - We performed combined operation for patients who have both ischemic heart disease
      and valvular heart disease in 21 cases from January 1991 to October 1999. This
      operation was 3.1% of 682 cases of coronary artery bypass grafting and 5.0% of
      416 cases of operation for valvular heart disease during that period. The mean
      age of these patients was 67.9 +/- 9.1 years. The average number of grafts in the
      coronary artery bypass grafting was 1.5 +/- 0.6. Aortic valve replacement was
      performed in 6 cases, mitral valve replacement in 10 cases and mitral valve
      plasty in 5 cases. Together with this combined operation, ascending aorta and
      aortic arch replacement was done in 1 case and abdominal aortic replacement in 2
      cases. Three patients died due to postoperative aortic rupture, cerebral
      infarction or excessive surgical intervention in ascending aorta and aortic arch
      replacement. Combined operation for ischemic heart diseases and valvular heart
      diseases can safely performed, but it appears necessary to pay attention to
      arteriosclerotic lesions.

PMID- 10935383
TI  - [Perioperative risk factors in valve surgery concomitant with coronary artery
      bypass grafting].
AB  - Between January 1990 and December 1999, 20 patients underwent the valve surgery
      concomitant with coronary artery bypass grafting. There were 16 males and 4
      females, their mean age was 66.5 years. Of the 20 patients, aortic stenosis was
      noted in 7, aortic regurgitation in 3, mitral stenosis in one, and mitral
      regurgitation in 9 patients. The cause of mitral regurgitation was considered to
      be an ischemic change in six patients, including ruptured papillary muscle due to
      myocardial infarction in two patients. On the contrary, LMT lesion was recognized
      in 5, LAD lesion in 17, LCX in 16, and RCA in 12 patients. Seven patients had
      preoperative myocardial infarction, three patients were required preoperative
      IABP support. AVR was performed in 10, MVR in 5, and MAP in 5 patients. The
      number of bypass was 1.9 +/- 0.85. Four patients died of LOS and MOF. The
      remaining 16 patients have been doing well. The significant difference between
      the survived and the not survived patients was recognized in the factor of
      emergency, preoperative IABP, papillary muscle rupture due to myocardial
      infarction, history of PTCA, LAD lesion, and the time of CPB. The factors
      regarding coronary artery had the influence on the outcome of a patients of valve
      surgery concomitant with CABG. Therefore, an appropriate myocardial protection
      and perioperative management for ischemia were mandatory.

PMID- 10935384
TI  - [Early and late results of combined valvular and coronary artery operations].
AB  - A total of 122 patients with ischemic heart disease underwent valvular surgery.
      Thirty-nine had combined CABG and aortic valve surgery (included Bentall method),
      72 had CABG and mitral valve operations, and 8 patients had CABG and double or
      triple valve operations. Only 3 patients for ruptured papillary muscle due to
      acute myocardial infarction had isolated mitral valve replacement. Early
      mortality was 5.1% AV, 2.8% MV and 12.5% DTV in the combined groups and 0% in the
      valve only group. The grafts patency rate was 93.5%. Univariate analysis of risk
      factors selected in the dialysis patients and the patients age older than 65
      years as the strongest predictors for early death. At the mean follow up period
      of 5.4 +/- 4.8 year after surgery, the 5-year all death free rates were 57.9 +/-
      9.6% AV, 69.6 +/- 5.8% MV and 75.0 +/- 15.3% DTV. The 5-year cardiac death free
      rates were 73.8 +/- 9.0% AV, 77.5 +/- 5.4% MD and 75.0 +/- 15.3% DTV.

PMID- 10935385
TI  - [Concomitant surgical resection of lung neoplasms and neighbouring organs].

PMID- 10935386
TI  - [Ruptured saccular aneurysm of a coronary artery to pulmonary artery fistula
      associated with cardiac tamponade].
AB  - We reported a case of ruptured saccular aneurysm of coronary artery to pulmonary
      artery fistula. The patient was a 59-year-old woman who was admitted for loss of
      consciousness and cardiogenic shock. Echocardiogram and computed tomography
      revealed cardiac tamponade. Rupture of saccular aneurysm of a coronary artery to
      pulmonary artery fistula was diagnosed by coronary angiography. Emergent
      pericardial drainage was performed, but she developed shock due to cardiac
      tamponade. The aneurysm was resected on a beating heart. The postoperative course
      was uneventful.

PMID- 10935387
TI  - [A case of acute pulmonary embolism fourteen days after hysterectomy].
AB  - We describe a 54-year-old female with acute pulmonary embolism. She showed a
      syncope attack and hypotension fourteen days after hysterectomy for uterine
      cancer. Preoperative echocardiogram revealed that thrombus in the right atrium
      was coming and going through the tricuspid valve. Emergent pulmonary embolectomy
      through the sternotomy under cardiopulmonary bypass was performed 4.5 hours after
      the diagnosis without homologous blood transfusion. Postoperative perfusion
      scintigram 20 days after the operation showed normal filling of the both lungs
      except for the localized defect at the distal portion of the right middle lobe.
      The patient was discharged on the 22nd postoperative day and she has been
      followed up with anticoagulation therapy. It is essential that we have the
      opportunity to salvage an otherwise helpless situation by a high index of
      suspicion and a prompt surgical intervention.

PMID- 10935388
TI  - [Right thoracotomy for reoperative mitral valve replacement].
AB  - We report a case of 67-year-old male who underwent reoperative mitral valve
      replacement through the right thoracotomy. He had undergone primary double valve
      replacement with mechanical valve for aortic valve and tissue valve for mitral
      valve respectively, and tricuspid annular plasty 11 years ago. The second
      operation was performed through the right thoracotomy under moderately
      hypothermic cardiopulmonary bypass. The mechanical valve was replaced via right
      side of left atrium approach under ventricular fibrilation at 25 centigrade of
      bladder temperature. He recovered well without any major complications.

PMID- 10935389
TI  - [Video-assisted thoracoscopic surgery for an intrapulmonary bronchogenic cyst: a
      case report].
AB  - A 23-year-old female was referred to us for an abnormal shadow at the right
      pulmonary hilum on chest X-ray film. CT scan of the thorax showed a cystic lesion
      measuring 4 x 3.5 cm with an air-fluid level in S3 of the right upper lobe. We
      performed video-assisted thoracoscopic S3 segmentectomy for this cyst. The
      pathological diagnosis was intrapulmonary bronchogenic cyst lined ciliated
      epithelium and contained bronchial glands, cartilage and smooth muscle.

PMID- 10935390
TI  - [A case of anterior mediastinal abscess with skin fistula resulting from
      descending necrotizing mediastinitis].
AB  - Descending necrotizing mediastinitis (DNM) is a serious, life-threatening
      infection. We present a case of anterior mediastinal abscess resulting from DNM.
      A 43-year-old woman, who had underwent cervical drainage for DNM 4 months ago,
      visited our hospital for cervical fistula. Chest CT revealed anterior mediastinal
      abscess. Mediastinal drainage through a subxiphoidal incision, debridement via
      the parasternal approach and resection of cervical fistula were performed without
      thoracotomy. A continuous mediastinal irrigation by acid water was performed
      postoperatively. The culture of the drain fluid became negative, and mediastinal
      abscess was disappeared. In conclusion, immediate and suitable drainage,
      debridement and postoperative-irrigation are important for DNM. On chronic stage,
      management to defend from extending infection is needed.

PMID- 10935391
TI  - [Three cases of pulmonary mucoepidermoid carcinoma].
AB  - Three cases of pulmonary mucoepidermoid carcinoma, which were surgically treated
      in our hospital, were reported. The first case was 28-year-old male, who had
      hemoptysis, underwent right upper lobectomy and mediastinal lymph node dissection
      on October 31, 1973. The tumor located and obstructed the ostium of right B2. The
      diameter was 2.3 x 1.8 cm. The second case was 63-year-old male, who had
      obstructive pneumonia, underwent left upper lobectomy and mediastinal lymph node
      dissection on November 18, 1998. The tumor located and obstructed the ostium of
      lingular bronchus, and the diameter was 1.8 x 1.2 cm. The third case was 25-year
      old male, who had obstructive pneumonia, underwent left sleeve lower lobectomy
      and mediastinal lymph node dissection on May 26, 1999. The tumor located in
      ostium of left B6, and it obstructed lower bronchus and expanded into the lung.
      The diameter was 4 x 2 cm. All cases were diagnosed as low grade malignancy with
      no lymph node metastasis. The first case survived without recurrence at least 5
      years as far as we followed, and the others are surviving until now without any
      signs of recurrence. These three cases were 0.19% of total resected lung cancers
      in our hospital from 1969 to 1999.

PMID- 10935392
TI  - [A case of mediastinal pseudocyst with unusual cystic findings in computed
      tomography].
AB  - We report here a case of mediastinal pseudocyst with unusual CT findings. A 25
      year-old woman was admitted to our hospital due to a chest abnormal shadow. She
      had a cystic mass which was located at anterior mediastinum and was adjacent to
      great vessels broadly without invasive findings. The intraoperative and
      histological findings revealed that the cystic mass was a pseudocyst which had
      been generated by the rupture of a thymic cyst to the mediastinum.

PMID- 10935393
TI  - [Pulmonary eosinophilic granuloma associated with recurrent pneumothorax: report
      of a case].
AB  - A 25-years-old male, current smoker, was referred to our department for treatment
      of the right pneumothorax due to pulmonary eosinophilic granuloma. He underwent
      thoracoscopic partial resection of the right lung. Immunostaining of the specimen
      revealed a lot of Langerhans cells positive for S 100 protein, suggesting active
      lesion. After cessation of smoking, no recurrence of pneumothorax or progression
      of disease have been observed for 13 months.

PMID- 10935394
TI  - [Hyperbaric oxygen as an adjunctive treatment for descending necrotizing
      mediastinitis: report of a case].
AB  - We report a case of 59-year-old man of descending necrotizing mediastinitis (DNM)
      secondary to peritonsillar abscess. A 59-year-old man with diabetes mellitus was
      admitted to a local hospital because of cervical swelling related to a
      peritonsillar abscess. Despite administration of antibiotics, swelling of the
      neck, dysphagia and dyspnea deteriorated. Therefore he was urgently undergone a
      tracheotomy and transferred to our hospital by an ambulance. The surgery
      consisted with neck and anterior mediastinal drainage through neck and cervical
      collar incision. Culture of drainage fluid showed clostridium difficile. On
      postoperative day 5, we started hyperbaric oxygen therapy (HBOT). After lavage
      and HBOT, the patient improved by degrees, and discharged on postoperative day
      82. DNM is a rare but serious complication of otopharyngeal and deep neck
      infection that spreads down to the mediastinum through the cervical-facial
      planes. Its mortality rate remains high even with aggressive surgical drainage
      and appropriate antibiotics. Our patient was successfully treated with urgent
      surgical drainage, antibiotics and HBOT. HBOT might be of great value as an
      adjunctive management to control this fatal infection.

PMID- 10935395
TI  - [Use of percutaneous cardiopulmonary support (PCPS) for extended surgery in
      patients with T4 tumor].
AB  - Since 1991, we have performed operations for tumors invading the upper airway,
      left atrium or main pulmonary artery with percutaneous cardiopulmonary support
      (PCPS) stand by support available. Of 15 cases with PCPS stand by, 6 patients
      actually underwent operation using PCPS. There were three esophageal cancers
      invading the carina, two lung neoplasms with left atrial invasion and one
      neoplasm extending to the main pulmonary artery. One of three patients with
      esophageal cancer had massive bleeding in the trachea resulting in airway
      obstruction. For this patient, emergency PCPS was carried out followed by the
      total removal of the thoracic esophagus and combined resection of membranous
      portion of the carina. As a result, a substantial amount of time (6 hours) was
      required. The two patients with reconstruction of the carina due to esophageal
      cancer were also successfully treated by using PCPS. Two patients with malignant
      pulmonary neoplasms invading the left atrium underwent combined resection of the
      lung and left atrium using a combination of PCPS and ventricular fibrillation
      under normothermia. In conclusion, PCPS should be accepted as a standard
      technique for patients with advanced thoracic malignancies in whom cardiac arrest
      or ventilation support is thought to be necessary for the complete removal of the
      tumor.

PMID- 10935396
TI  - [Delayed sternal closure after open heart surgery in neonates and early infants].
AB  - Between November 1992 and February 1996, 84 patients (less than 3 months of age)
      underwent open heart surgery. Among 76 patients except 8 who required mechanical
      circulatory support, the sternum was left open. The indication of open sternotomy
      was hypoplastic left heart syndrome in 14 patients and unstable hemodynamics in 4
      patients. Three patients died before delayed sternal closure. Delayed sternal
      closure was carried out in 15 patients with a mean of 4.7 days postoperatively.
      By the time of sternal closure, blood pressure, left atrial pressure and
      respiratory parameters improved and inotropics were reduced with the minus fluid
      balance. One patient died of sepsis 4 days after delayed sternal closure. Delayed
      sternal closure was effective modality to neonates or early infants after complex
      open heart surgery.

PMID- 10935397
TI  - [Simultaneous abdominal aortic replacement and thoracic stent-graft placement for
      multiple aortic aneurysms: report of a case].
AB  - Patients with aneurysmal disease involving both the thoracic and abdominal aorta
      have historically required simultaneous or sequential conventional operations.
      Staged operations were generally preferred, but we experienced that a patient had
      rupture of the second aneurysm after he finished initial treatment for the first
      aneurysm. We have implemented simultaneous operation using thoracic stent-graft
      placement. A 78-year-old male who had multiple aortic aneurysm involving both the
      thoracic and abdominal aorta underwent conventional abdominal aortic replacement
      with endovascular stent-graft placement into the distal arch of the thoracic
      aorta under fluoroscopic guidance. The stent-graft was composed of two units of
      self-expanding stainless-steel Z stent covered with an thin wall woven Dacron
      graft. Postoperative aortography showed no stent migration and no endoleak.
      Simultaneous abdominal aortic replacement and deployment of a thoracic stent
      graft may be a valuable treatment option for these patients. However, careful
      long term follow up is necessary to prove the value and the effects of the
      endovascular treatment.

PMID- 10935398
TI  - [A case treated surgically through anterior axillary thoracotomy for recurrent
      right spontaneous pneumothorax after repeated video-assisted thoracoscopic
      surgery].
AB  - A 21-year-old male who had thoracoscopic surgery for right spontaneous
      pneumothorax was admitted to our hospital complaining of dyspnea due to the
      recurrence. There was no bulla in right apex but empysematous change in visceral
      pleura at re-thoracoscopic surgery. Two bulla in right S6 were removal using endo
      stapler. Three years after the second thoracoscopic surgery, the recurrence of
      right pneumothorax was recognized. Chest CT revealed a new bulla in right apex.
      Therefore the third operation was carried out through anterior axillary
      thoracotomy. A new bulla was resected with endo-stapler and pleurodesis using
      argon laser was also applied to prevent of recurrence of pneumothorax. The
      patient is now doing well without recurrence 6 months after the third operation.

PMID- 10935399
TI  - [The effects of aerobic training on the emotional response in patients who
      underwent cardiac surgery].
AB  - It has been reported that cardiac surgery and aerobic training influence the
      patient's emotional response. We investigated the changes in emotional response
      before and after cardiac surgery and during aerobic exercise training as a
      cardiac rehabilitation using profile of mood states (POMS). Subjects were thirty
      five patients (25 men and 10 women, average 57 years) who underwent cardiac
      surgery. All patients participated in the rehabilitation program which included
      aerobic exercise training after cardiac surgery. Aerobic training consisted of
      cycle ergometer or treadmill. Emotional states were evaluated by POMS score at
      the preoperative phase, early postoperative phase (about 10 days after surgery)
      and aerobic training (about 20 days after surgery). Most of the emotional state
      (tension, anxiety, anger and hostility) significantly improved after cardiac
      surgery. In particular, aerobic training has an additional effect for improving
      one of the emotional state which is tension and anxiety. However, several factors
      such as deconditioning, postoperative complications and high age delayed the
      improving of emotional response.

PMID- 10935400
TI  - [Coronary artery bypass grafting using side-to-side anastomosis].
AB  - Recently, to obtain better long-term patency after coronary artery bypass
      grafting (CABG) arterial conduits such as internal mammary arteries (IMAs) and
      the right gastroepiploic artery have been frequently used. For coronary site
      anastomosis, end-to-side anastomosis is common. These conduits have a smaller
      diameter than the saphenous vein graft, so that, usually, longitudinal slits are
      made on the distal end of these grafts to obtain a more effective anastomotic
      orifice area. However, there is a potential for anastomotic leakage due to
      mismatch between the incision of the coronary artery and the arterial graft. We
      report here the efficacy of side-to-side anastomosis using small arterial
      conduits. This method has several advantages. Firstly, there is no chance of
      anastomotic leakage, since the coronary incision and graft incision can be
      perfectly matched. Secondly, if there is at least a 5-mm distance between the
      distal end of the graft incision and the surgical clip, the graft incision can be
      extended during anastomosis for adjustment. Thirdly, the distal end of the graft
      can be held beyond the surgical clip by forceps without damaging the arterial
      graft, which makes it easier for the anastomosis to be performed. Finally, the
      anastomosis can be checked by passing a probe through the distal end of the graft
      after removing the surgical clip. Also dye can be injected from the distal end of
      the graft at "Off Pump CABG", intraoperatively. This technique can be applied not
      only for distal end anastomosis, but also for proximal end, using free IMA to the
      ascending aorta and to make a Y-graft.

PMID- 10935401
TI  - [An availability and selection of magnifying glass in fine operative techniques].
AB  - In recent years, much attention has been paid to minimally invasive surgery from
      standpoints of quality of life for the patients. It is very important to use
      magnifying glass for achieving these purposes. However, there are not
      satisfactory glasses for operative techniques such as coronary artery bypass
      grafting and microsurgery in the several surgical fields with lightness, wild
      visual field and cost-effectiveness. Now a days, satisfactory glass is
      commercially available which can be used in fine operative techniques in the
      several fields. With this glass fine operative procedures can be performed and
      good operative results might be obtained in deed.

PMID- 10935403
TI  - [Relatively non-curative resection for lung cancer: is this a complete
      resection?].
AB  - A superior outcome is observed for cases of curative resection compared with that
      of non-curative resection. The Japan Lung Cancer Society revised "General Rule
      for Clinical and Pathological Record of Lung Cancer" in 1999 and relatively non
      curative resection (RNCR) of former rule was categorized as complete resection.
      The reason and the countermeasure of RNCR for lung cancer were analyzed. During
      11 years, 242 patients with primary non-small cell lung cancer were surgically
      treated in Showa University Hospital. One hundred patients underwent absolutely
      curative resection (ACR); 64, relatively curative resection (RCR); 55, RNCR; 23,
      absolutely non-curative resection (ANCR). Three-year survival was 90% for
      patients with ACR, 48% with RCR, 21% with RNCR, and 13% with ANCR. The cases for
      RNCR were defined as follows: RNCR-a) incomplete mediastinal lymph node
      dissection (n = 29), RNCR-b) partial resection of the lung without lymph nodes
      dissection (n = 5), RNCR-c) N 2 b metastasis (n = 14), RNCR-d) N 3 lymph node
      dissection with N 3 metastasis (n = 0), RNCR-e) metastasis in other lobes of the
      ipsilateral thoracic cage (n = 7). RNCR-a) was selected in the poor risk patients
      who were diagnosed as clinical N 0 or N 1. Only one out of the 29 patients was
      diagnosed as pathological N 2 after surgery with hilar and mediastinal lymph node
      sampling. Because of the excellent preoperative staging, only RNCR-a) had three
      year survivors among RNCR cases and the three year survival rate was 39%. RNCR-b)
      was selected in the severe risk patients who were diagnosed as clinical N 0.
      There was no death associated with complication in RNCR-b) group. Some cases of
      RNCR-c) (pathological N 2 b) were clinical N 0 or N 1 and there was a limitation
      of the preoperative clinical staging. However, some cases of the clinical N 2
      were surgically treated with chemo-radiotherapy and were resulted as RNCR-c). The
      concepts between curative resectability and complete resectability are different
      and RNCR-b), c), and e) should not include the curative resection because of the
      poor prognosis.

PMID- 10935402
TI  - [Thromboembolic and bleeding complications in patients treated with oral
      anticoagulant therapy after mechanical heart valve prostheses implantation].
AB  - Thromboembolic and bleeding events are major cause of morbidity and mortality in
      patients with mechanical heart valves. Ninety-three patients had been received
      anticoagulant (warfarin with bucolome 300 mg) for mechanical prosthetic valves,
      and the regulation of anticoagulation was performed within a prothrombin time
      international normalized ratio (PT-INR) about 2.0 of normal. The mean duration of
      follow-up was 64.1 months, and the total duration of follow-up was 496.8 patient
      years (py). The valve related complications occurred in 10 cases (2.0 per 100
      py). Anticoagulant related hemorrhagic events occurred in 7 cases, and valve
      thrombosis in 3 cases. All three cases of valve thrombosis were in cases with
      Bjork-Shiley valve at the mitral position. An artificial valve in mitral position
      increased the valve related risk compared with the aortic position (3.1%/py vs
      0.0%/py). Bileaflet valve showed a lower incidence of thromboembolism than
      tilting disc valve (2.3%/py vs 0.0%/py). The risk of valve related complication
      varied with the type and the position of the prosthesis, it is desirable that the
      intensity of anticoagulation would be changed according to the prosthetic valve
      type and its position. These results suggest that the intensity of
      anticoagulation is optimal when the PT-INR is 1.8-2.0 for patients with bileaflet
      valve in the mitral position, and is 1.6-1.8 in the aortic position. Tilting disc
      valve needs more intensity of anticoagulation, and needs additional antiplatelet
      agent in the mitral position.

PMID- 10935405
TI  - [Five cases of surgically resected chronic expanding hematoma in the chest].
AB  - We report surgically treated 5 cases of chronic expanding hematoma in the chest.
      Three were male and two were female, aged 53 to 76. All patients except one who
      was thought to have an early stage of chronic expanding hematoma, had severe
      dyspnea due to compression of lung parenchyma or heart. Complete removal of the
      hematoma with fibrous capsule was done in two cases, but in three cases the
      hematoma was removed but the capsule was not because of severe adhesion to the
      surrounding structures. Post operative course was different to each other. One
      patient whose capsule was not removed completely have recurrent hematoma in the
      chest. The pulmonary or cardiac function were improved greatly except for the two
      cases; an early stage case and a recurrent case. We conclude that surgical
      removal is the first treatment for chronic expanding hematoma and complete
      removal of it with capsule is recommended.

PMID- 10935404
TI  - [Clinical study of aortic root replacement].
AB  - From 1990 to 1999, 19 patients underwent aortic root replacement. Annulo-aortic
      ectasia was observed in 14 patients, aortic dissection in 4, and aortitis in 1.
      Mean aortic cross-clamp times and cardiopulmonary bypass times were 163 +/- 44
      and 247 +/- 99 min, respectively. Concomitant procedures were coronary artery
      bypass grafting in 3 patients, aortic arch replacement in 1 and aortic arch
      replacement and elephant trunk method in 2. There were two hospital deaths due to
      cardiac failure. There was one late death because of pharyngeal cancer 1.7 years
      after the operation. Seventeen survivors were followed for a mean duration of 4.4
      years (0.6-9.3 years). There were no complications during this period. In
      conclusion, good results were obtained by modified Bentall operation.

PMID- 10935406
TI  - [Video assisted thoracic surgery for the treatment of catamenial pneumothorax].
AB  - Video assisted thoracic surgery (VATS) was applied in 3 cases of pneumothorax
      combined with pathologic changes in the diaphragm (two cases of catamenial
      pneumothorax and one case of suspected catamenial pneumothorax). Case 1, 39-year
      old woman, was preoperatively diagnosed as catamenial pneumothorax in the right
      lung. Thoracoscope was inserted through the 5th intercostal anterior axillary
      line and the lesion with the pathologic changes in the central tendon of the
      diaphragm was incised and sutured with Endo-GIA and Endo-STAPELAR. Case 2, 42
      year-old woman, was confirmed to have pathologic changes in the central tendon
      after insertion of thoracoscope through the 5th intercostal anterior axillary
      line. Minithoracotomy of 50 mm in size was added close to the center of the
      diaphragm and direct incision and suture of that part were performed. Case 3, 47
      year-old woman, underwent thoracoscopy through the 5th intercostal mid-axillary
      line and bulla in the S2 interlobar surface was incised with Endo-GIA. In this
      case, the diaphragm was partially incised through additional minithoracotomy
      because some lesions were detected on that part. VATS can fully be carried out
      for pathologic changes in the diaphragm in catamenial pneumothorax. Since
      catamenial pneumothorax may be complicated with another pathologic changes in the
      diaphragm (Case 1) or in the visceral pleura (Case 3), the whole thoracic cavity,
      including diaphragm and visceral pleura, should be carefully observed under
      thoracoscopy. Application of minithoracotomy-associated thoracoscopic surgery is
      a useful method in the case to whom catamenial pneumothorax is definite or
      suspected.

PMID- 10935407
TI  - [A case report of aneurysm of the ductus arteriosus combined with mitral
      regurgitation].
AB  - A case with the giant aneurysm of the ductus arteriosus combined with severe
      mitral regurgitation is reported. 58-year-old male underwent MVR and patch
      closure of the ductal orifice for staged operation. The first operation was MVR
      and patch closure of the PDA orifice of the pulmonary artery end using retrograde
      cerebral perfusion (RCP) with deep hypothermic circulatory arrest (DHC). The
      second operation was performed on 3 months after the first operation using left
      thoracotomy approach, and patch closure of the ductal orifice via the aorta using
      RCP with DHC was performed. Upon following-up examination, the patient is now
      doing well 20 months after the initial surgery.

PMID- 10935409
TI  - [A case report of treatment for tracheal fistula after radical esophagectomy].
AB  - We report our experience of the treatment of a 60-year-old man with upper
      tracheal fistula which developed on the 11th day after radical surgery for
      esophageal cancer. Primary treatment to close the fistula was unsuccessful,
      resulting in the involvement of empyema due to infection. Controlled ventilation
      with T-tube and drainage through a chest tube for 2 months lead to depuration of
      the thoracic cavity. As a strategy for secondary closure of the fistula,
      fenestration was performed on the 87th day postoperatively. The patient's overall
      condition improved thereafter and closure was being considered. However, the
      patient died on the 116th day postoperatively due to supervenient aspiration
      pneumonia. Thus, long-term controlled ventilation with a T-tube was beneficial
      for the treatment of central airway injury.

PMID- 10935410
TI  - [Thoracoscopic resection for benign solitary fibrous tumor of the parietal
      pleura].
AB  - We have experienced thoracoscopic surgery for benign solitary fibrous tumor of
      the parietal pleura. A 46-year-old woman was admitted to our hospital because of
      chest abnormal shadow. Under thoracoscopy the tumor that was connected to the
      parietal pleura with a wide pedicle was completely resected with combined
      parietal resection of the pleura. Pathological diagnosis was a benign solitary
      fibrous tumor developed from the connective tissues under the parietal pleura.
      Thoracoscopic surgery is well indicated for a solitary fibrous tumor and wide
      excision of the tumor with combined resection of the pleura is important to
      prevent a local recurrence.

PMID- 10935411
TI  - [Pulmonary cryptococcosis diagnosed by video-assisted thoracoscopic surgery with
      CT-guided localization: report of a case].
AB  - We report a case of pulmonary cryptococcosis diagnosed by video-assisted
      thoracoscopic surgery (VATS) with CT-guided localization. A 61-year-old man was
      admitted to our hospital for the precise diagnosis of a solitary mass in the left
      upper lung. Because the mass was too small to be detected under VATS, we tried CT
      guided localization for surgery. One day before VATS, we placed a marking device
      besides the lesions after percutaneous puncture. We used a Naruke point marker as
      a marking device. After this procedure, the wedge resection was performed. The
      pathological diagnosis was cryptococcosis of the lung. The identification of
      small lesions in the lung has frequently been detected by helical and thin slice
      CT. Therefore, CT-guided localization procedure may be the most reliable
      technique to employ before surgery.

PMID- 10935408
TI  - [Double valve replacement without blood transfusion in a case complicated with
      liver cirrhosis and pancytopenia].
AB  - A 63-year-old woman complicated with liver cirrhosis and pancytopenia was
      admitted for aortic and mitral valve replacement. As laboratory findings at time
      of admission showed pancytopenia with Hb of 7.3 g/dl, WBC of 2,200/mm3, and
      platelet of 6.2 x 10(4)/mm3, splenectomy was first conducted and the blood cells
      and platelet increased in number. At 27 days after splenectomy, double vale
      replacement was performed without blood transfusion and her postoperative course
      was unevenfull. It is considered that preoperative splenectomy is useful in
      management of patients complicated with hypersplenism and pancytopenia.

PMID- 10935412
TI  - [A case of G-CSF-producing large cell carcinoma of the lung with gastric
      metastasis].
AB  - We report a rare surgically-treated case of G-CSF-producing large cell carcinoma
      of the lung with gastric metastasis. A 65-year-old male was admitted to our
      hospital because of fever, anemia and epigastralgia. Chest X-ray examination and
      CT scanning revealed a round mass shadow (8 cm) in contact with the chest wall in
      the right upper lung field and metastasis to the mediastinal lymph nodes.
      Laboratory examination showed a WBC of 16,800/mm3, CRP of 11.6 mg/dl, and a serum
      G-CSF of 90 pg/ml. Upper gastrointestinal series and gastroscopy showed an
      ulcerating submucosal tumorous lesion in the pyloric antrum. The lung carcinoma
      was treated by right upper lobectomy with chest wall resection. After 1 month,
      gastrectomy was performed. After the operation, the WBC normalized, and the CRP
      and serum G-CSF levels decreased. Histopathological examination demonstrated a
      poorly differentiated large cell carcinoma in the lung and a metastatic lesion in
      the stomach. Immunohistochemical staining with anti-G-CSF mono-clonal antibody
      showed negative results in the lung but positive results in the stomach. He was
      discharged 3 weeks after gastrectomy but died of aggravation of the general
      condition associated with local recurrence in the chest wall 2 months after
      discharge.

PMID- 10935413
TI  - [Dementia screening in psychiatric consultation for elderly patients in a general
      hospital].
AB  - BACKGROUND: Elderly patients on medical-surgical wards in general hospitals often
      suffer from cognitive dysfunction that hampers medical treatment of somatic
      diseases. Symptoms of cognitive dysfunction may not be recognized adequately by
      non-psychiatric physicians. PATIENTS AND METHOD: We studied the usefulness of a
      short screening instrument for cognitive dysfunctions (short mini mental state
      test) in a consecutive sample of 222 psychiatric consultation liaison patients
      older than 60 years of age. Normative data for the screening test from an
      epidemiological sample, the Berlin Aging Study, are given and compared with the
      consultation sample. RESULTS: Mild to moderate deficits in cognitive functions
      were found in 32% of patients, severe deficits indicating dementia- or delirium
      syndromes were found in 17.7%. Applying the cut off 4/5, 88.9% correct
      classifications of dementia patients were obtained. The item analysis
      demonstrates significant differences with respect to the age-matched population
      sample for the orientation items, the 2nd and subsequent subtractions of the
      serial seven task and, to a lesser degree, the memory items. CONCLUSION: A
      standardized assessment of the 15 items of the SMMS represents a practical,
      reliable and valid screening for relevant cognitive deficits, which may also
      serve as documentation of the time course especially in acute organic-psychiatric
      syndromes.

PMID- 10935414
TI  - [Cost-benefit analysis of an evidence-based secondary prevention of coronary
      heart diseases by statins. An analysis for Germany from a social security
      perspective].
AB  - BACKGROUND: Lowering of the cholesterol level is of central importance in the
      prevention of coronary heart disease. Although the clinical benefits of treatment
      with statins have been shown in numerous studies, economic considerations are
      also being taken increasingly into account for the decision process about health
      care benefits. With this background, a cost-benefit analysis was carried out for
      statin treatment. METHODS: Based on a cost analysis for coronary heart disease
      carried out by the authors from a social security standpoint, the net prevention
      costs for secondary prevention in Germany were assessed. The ICD-9 codes 410-414
      were assigned to coronary heart disease. In addition to the direct costs of
      treatment for coronary heart disease, loss of premiums for social security,
      savings on old age pensions, related pension claims and wage compensations over a
      time period of 10 years were also quantified in the cost analysis. Furthermore,
      prevention through medication for the 45- to 64-year-old coronary heart disease
      patients was considered. Costs for prevention were assessed on the basis of the
      mean dosages of all medications on the market according to the Rote Liste (German
      Formulary). A risk reduction of 30% was assumed and numerous univariate
      sensitivity analyses were carried out. RESULTS: Depending on which parameters
      were varied, there were pronounced differences in the results. The most
      favourable cost-benefit relation was achieved for the preventive measures in
      400,000 patients with net prevention costs of 1.08 billion DM (2.16 billion DM
      for 800,000 patients) for a duration of medical preventive care of 5 years. The
      highest net prevention costs of 3.47 billion DM for 400,000 coronary heart
      disease patients (or 6.93 billion DM for 800,000 patients) resulted when maximum
      prices for statins were assumed. In the setting taken as base analysis,
      approximately 25% of the prevention costs are accounted for by cost saving
      through prevention. DISCUSSION: The transfer of clinical study results into
      clinical practice is associated with uncertainties which necessitate
      comprehensive sensitivity analyses. The costs of coronary heart disease were
      shown to be highly sensitive to the cost-benefit relationship. Although from an
      overall social security perspective, the direct costs of treatment and the loss
      of premiums were balanced by reduced expenditure (pension savings), coronary
      heart disease does lead to a financial burden on the social security. CONCLUSION:
      This financial burden is decreased by prevention of coronary heart disease. Part
      of the costs of statin therapy can be covered in every situation by cost savings
      through the avoidance of coronary heart disease. Even complex simulation models,
      that uses realistic assumptions, could only determine the costs of an evidence
      based secondary prevention of coronary heart disease unprecisely, because the
      worst case and the best case vary with the factor 7.

PMID- 10935415
TI  - [Update in infectious diseases. Part I: epidemiology].
AB  - A number of infectious agents has been newly detected in the last 10 years.
      Climatic changes and migration have been the most important factors in the
      emergence of new and old infections. Additionally, new methods for the detection
      of DNA and RNA have played an important role in the detection of agents difficult
      to culture. Relevant new bacterial pathogens are Bartonella henselae (cat scratch
      disease, bacillary angiomatosis), Tropheryma whippeli (Whipple's disease) and new
      Rickettsiae. Newly detected viral pathogens include Sin-nombre virus (pulmonary
      Hanta virus syndrome), Nipah- and Hendra virus and avian influenza. Bovine
      spongiform encephalopathy has been transmitted to humans causing the newly
      described syndrome of variant Creuzfeldt-Jakob disease. The extent of this new
      epidemic is not yet clear. These trends from the last years clearly indicate,
      that further new infections and infectious agents will be detected in the future.

PMID- 10935416
TI  - [Career opportunities for female and male physicians in the pharmaceutical
      industry].
AB  - INTRODUCTION: Pharmaceutical medicine is not only a mainstay in clinical drug
      development and marketing of drugs in pharmaceutical industry but also a
      challenging alternative to the clinic and outpatient practice for physicians.
      Since most of them have only a vague notion of what a career in this sector of
      industry involves, this paper attempts to display the scope of opportunities and
      responsibilities for physicians and to answer some of the most frequently asked
      questions. JOB PROFILES: Areas for physicians are preclinical research, clinical
      research, drug safety, biometry, scientific relations, marketing and sales
      departments, working as company physician, training of sales representatives,
      health policy and project management. Earnings, continued and postgraduate
      training, job changing as well as possibilities of information on a career in the
      pharmaceutical industry are described. CONCLUSION: Despite the wide range of job
      profiles, a physician is still a physician in the pharmaceutical industry: his or
      her aim is to help patients and relieve their suffering through ethical and
      innovative therapeutic research. This aim is achieved through committed
      involvement in the development and marketing of new, effective and safe drugs.

PMID- 10935418
TI  - [Dangerous tropics].

PMID- 10935417
TI  - [Osteoporosis in the male].
AB  - BACKGROUND: Osteoporotic fractures occur frequently also in men. Epidemiologic
      data from Germany indicate that more than 900,000 men are affected by
      osteoporotic fractures. Diagnosis and therapy of male osteoporosis are hampered
      by a lack of clinical studies. DIAGNOSIS: Risk factor analysis, conventional
      spine X-rays, bone densitometry and a limited number of serum and urine analyses
      contribute to the diagnosis of osteoporosis and the assessment of future fracture
      risk. Bone densitometry at the femoral neck is superior to measurements at the
      lumbar spine because of the high prevalence of degenerative changes at the lumbar
      spine in elderly men. Major risk factors for osteoporosis are hypogonadism,
      glucocorticoid therapy, hypercalciuria, gastrointestinal disease, and high
      alcohol consumption. In individual cases, bone histology or additional
      biochemical studies are needed to establish the cause of osteoporosis. THERAPY:
      Calcium and vitamin D deficits should be substituted both in prevention and
      treatment of male osteoporosis. Testosterone replacement therapy is effective in
      hypogonadism. In primary osteoporosis and in corticosteroid-induced osteoporosis,
      bisphosphonates (cyclical etidronate, alendronate) and fluorides are therapeutic
      options. CONCLUSION: Important principles in the care of men with osteoporosis
      are the transfer of knowledge established for postmenopausal osteoporosis and the
      rigorous search for secondary osteoporosis aiming at treatment of the underlying
      cause. Large prospective randomized trials aiming at the reduction of fracture
      rate in male osteoporosis are missing. They are urgently needed.

PMID- 10935420
TI  - [Ischemic colitis as a primary manifestation of an embolizing small-cell
      bronchial carcinoma infiltrating a pulmonary vein].
AB  - CASE REPORT: A 59-year-old male patient was admitted to hospital for general
      malaise with muscle and bone pain. Some weeks ago he had been treated with
      roxithromycin because of pneumonia. Physical examination revealed melena.
      Hemoglobin was 7.6 g/l. Endoscopy of the upper gastrointestinal tract did not
      show a bleeding source. Colonoscopy and histologic examination revealed
      hemorrhage caused by ischemic colitis. To rule out cardiac embolies in the
      presence of paroxysmal tachyarrhythmia absoluta a transesophageal echocardiogram
      was performed. A mediastinal mass infiltrating the upper left pulmonary vein was
      detected. The mass had not been visible on routine chest X-ray. Histologic
      examination of a bronchoscopically taken specimen revealed an oat-cell bronchial
      carcinoma. CONCLUSION: In this patient invasion of a pulmonary vein by the
      bronchial carcinoma lead to embolies which caused mesenterial ischemia. According
      to our researches this is the first report of ischemic colitis as a manifestation
      of bronchial carcinoma.

PMID- 10935419
TI  - [Lassa fever].
AB  - A 22-year-old female German student was admitted with fever of unknown origin for
      5 days to the hospital of her hometown immediately after returning from a 7-week
      journey under simple conditions through 4 West African countries. After exclusion
      of malaria and typhoid and nonrespondence to antibiosis, she was transferred on
      the 4th day to the Department of Tropical Medicine in Wurzburg. After the
      clinical assumption of Lassa fever, the virus was confirmed by PCR within 3 hours
      (Bernhard Nocht Institute, Hamburg) on the 10th day of her illness. The
      assumption was based on travel history, continuous fever, cough, pharyngitis,
      thoracic pain, and exclusion of other acute infections. From the beginning, the
      patient was cared for with barrier nursing and after diagnosis under strict
      isolation in an intensive care unit reserved for her alone by a team of doctors
      and nurses specialized in tropical medicine and intensive care. The staff was
      protected through isolation suits with filters. Monitoring and therapy entailed
      all methods of intensive care and intravenous administration of ribavirin 16
      mg/kg body weight = 900 mg every 6 hours. The patient died on the 14th day of her
      illness in a volume deficiency shock due to uncontrollable heavy hemorrhage from
      all organs including the skin, a so-called "leakage syndrome". CONCLUSION:
      Conclusions are drawn regarding training in tropical medicine, diagnostics of
      highly contagious infections, intensive care of patients affected with them under
      isolation, contact tracing, psychological crisis intervention for personnel,
      media information, care of the infectious corpse and disposal of infectious
      waste.

PMID- 10935421
TI  - [Classic case of benign recurrent intrahepatic cholestasis (Summerskill-Halshe
      Tygstrup syndrome)].
AB  - BACKGROUND: The benign recurrent intrahepatic cholestasis is an autosomal
      recessively inherited liver disease. The gene was mapped to a region on
      chromosome 18q21-22. Because of its rareness this disease is first considered in
      the differential diagnosis of cholestasis after many years of extensive
      investigations. CASE REPORT: We report about a 17-year-old patient, who suffered
      from intermittent attacks of cholestatic jaundice and pruritus. Clinical course,
      laboratory data and invasive investigations led to the diagnosis of a typical
      case of benign recurrent intrahepatic cholestasis (Summerskill-Walshe-Tygstrup
      syndrome). CONCLUSION: This disease is remarkable for a discrepancy between a
      rise of serum bile acids at the onset of each attack and a later rise of
      bilirubin. Typically high bilirubin levels are noted, and bilirubin can even
      reach more than 50 mg/dl. The serum alkaline phosphatase is increased, too,
      whereas the values for the transaminases and gamma GT are normal or only slightly
      elevated. Histological studies reveal a cholestasis, bile plugs in the bile
      canaliculi, a perilobular fibrosis and inflammatory infiltrations of the
      periportal zones. Differential diagnosis includes an abundance of diseases with
      cholestasis. Treatment is difficult, purely symptomatic and often without marked
      effect. Nevertheless prognosis is good, histories of about 50 years were without
      evidence of progression to cirrhosis.

PMID- 10935422
TI  - [Sweet syndrome--a rare cutaneous complication of Crohn's disease].

PMID- 10935423
TI  - Inadequate pharmacotherapeutic data for drugs used in children: what can be done?
AB  - Although infants and children are affected by many acute and chronic diseases,
      nearly 80% of the drugs approved in the US for use in adults have not been
      labelled for paediatric use. This leads to the 'off-label' use of drugs which may
      produce suboptimal efficacy or harmful effects. Recent regulations proposed by
      the US Food and Drug Administration (FDA) require the industry to conduct
      paediatric studies in certain situations. However, some incentives will be
      provided to the industry to seek paediatric labelling. Paediatric practitioners
      and researchers will play an active role in conducting research and disseminating
      data about medication use in infants and children. However, increased funding is
      required for paediatric research. Industry, government, associations, academia
      and the public should work together to develop an agenda for action, with the
      goal of improving clinical outcomes and quality of life in infants and children.

PMID- 10935424
TI  - Wilms tumour: diagnosis and treatment.
AB  - Wilms tumour is the most common intra-abdominal solid tumour of childhood.
      Treatment includes surgical resection and chemotherapy for virtually all affected
      children and additional radiotherapy for those with advanced disease or adverse
      prognostic features. This approach leads to cure rates exceeding 80%. During the
      last decade there have been a number of advances which have increased our
      understanding of the biology of Wilms tumour. The development of Wilms tumour,
      for example, involves several genes, including WT1, the Wilms tumour suppressor
      gene at 11p13, and WT2, the putative Wilms tumour suppressor gene at 11p15. In
      addition, certain chromosomal regions, most notably 16q and 1p, might predict
      outcome and hence serve as a prognostic factor, useful for determining the
      intensity of therapy. This novel information is now being incorporated into
      current therapeutic protocols. We reviewed the medical literature and present a
      summary of the advances made, outlining the current treatment of Wilms tumour.
      Future protocols will continue incorporating biological markers. The goal is to
      identify patients at low risk for relapse, which will allow a reduction in
      treatment intensity and subsequent toxicity. Children at an increased risk for
      relapse can be selected for more intensive treatment.

PMID- 10935426
TI  - Treatment of otitis externa in children.
AB  - Inflammation of the external auditory canal can be localised or diffuse, and
      acute or chronic. Predisposing conditions include external trauma, loss of the
      canal's protective coating, maceration of the skin from water or humidity, and
      glandular obstruction. Acute otitis externa is generally caused by Pseudomonas
      aeruginosa or Staphylococcus aureus. Management of patients with otitis externa
      includes debridement, topical therapy with acidifying and antimicrobial agents,
      and systemic antimicrobial therapy when indicated. The management of patients
      with chronic otitis externa includes cleansing and debridement accompanied by
      topical acidifying and drying agents. This is followed by topical antibiotics and
      corticosteroid preparations. Surgery is mainly used to allow cleansing and
      aeration and/or removal of the scarred tissue. Patients with acute localised
      otitis externa (furunculosis) are treated with local heat and systemic
      antibiotics in the inflammatory stage, and drainage in the abscess state. Mycotic
      external otitis is managed with topical acidifying and antifungal agents, while
      viral (herpes) infection is treated with topical and systemic aciclovir
      (acyclovir). Patients with necrotising (malignant) external otitis, which is
      mainly caused by P. aeruginosa and S. aureus, are treated with systemic
      antibiotics and, rarely, by surgical debridement. Therapy for eczematous otitis
      externa is first directed at the secondary infection, and thereafter at the
      primary dermatological condition. Prevention of recurrent external otitis is
      aimed at minimising ear canal trauma and the avoidance of exposure to water.
      Preventative use of topical acidifying agents or 70% alcohol is also advocated.

PMID- 10935427
TI  - New perspectives in the drug treatment of Kawasaki disease.
AB  - Kawasaki disease (KD) has become the leading cause of acquired heart disease in
      developed countries. Conventional therapy for KD includes intravenous
      gammaglobulin (2 g/kg as a single dose over 12 hours) and aspirin
      (acetylsalicylic acid; high dose until the fourteenth day of illness then low
      dose). Therapy administered within the first 10 days of the onset of the illness
      has been shown to reduce arterial wall inflammation and thereby prevent the
      development of coronary artery aneurysm formation. The majority of patients with
      KD will respond to conventional therapy. However, the management of nonresponders
      and patients with complications (such as acute thrombosis and chronic coronary
      artery changes) remains controversial. In this review article, we address some of
      these controversies and also describe newer treatment modalities that have been
      used in the management of patients with KD, both in the acute and convalescent
      stages of the disease.

PMID- 10935425
TI  - Recognition, treatment and complications of meningococcal disease.
AB  - Meningococcal disease remains a major cause of death in young children. A
      decrease in mortality requires recognition and treatment of the disease at a
      number of stages in the illness. Life-threatening meningococcal disease usually
      presents as septicaemia rather than meningitis. The cardinal feature of
      meningococcal septicaemia is the purpuric rash. Many parents recognise the rash
      and seek medical advice because of it. When primary care physicians recognise the
      rash, the administration of parenteral penicillin may decrease mortality.
      However, antibacterials are not given promptly if there is no rash or if the
      disease presents in an atypical form. In hospital, antibacterial therapy with a
      third-generation cephalosporin should be given. Disease severity needs to be
      assessed by a valid method, such as the Glasgow Meningococcal Septicaemia
      Prognostic Score (GMSPS). This can identify those patients who need intensive
      care and/or might benefit from new therapies. The 2 life-threatening
      complications are septic shock and meningoencephalitis with raised intracranial
      pressure. Despite numerous case reports of success with potential new treatments,
      none has been proven safe and/or effective by controlled trials. Although it is
      tempting to focus on new treatments, the early recognition of severe
      meningococcal disease by parents, primary care physicians and junior hospital
      doctors is equally, if not more, important as a potential means of decreasing
      mortality.

PMID- 10935428
TI  - Treatment of tuberculous infection and disease in children: the North American
      perspective.
AB  - The standard preventive therapy for paediatric patients with tuberculous
      infection centres on isoniazid therapy. The chosen regimen of isoniazid therapy
      is based on individual patient factors. In the case of known or suspected
      resistance, combination therapy [e.g. isoniazid and rifampicin (rifampin)] or
      alternative therapies (e.g. pyrazinamide, a fluoroquinolone and/or ethambutol)
      should be employed. The goal of treatment of tuberculous disease is to achieve
      sterilisation in the shortest possible time. More intensive multiple drug
      combination regimens (e.g. isoniazid, rifampicin and pyrazinamide) have resulted
      in successful 6- and 9-month treatment regimens in children. If drug resistance
      is suspected then a fourth drug is added to the initial treatment regimen and the
      length of therapy may be extended to 18 months. The paediatric information
      available on the commonly used antituberculous agents (e.g. isoniazid,
      rifampicin, pyrazinamide and ethambutol) is reviewed in this article. Agents are
      described with an emphasis on their formulation availability, mechanism of
      action, pharmacokinetic properties (e.g. absorption, distribution, metabolism and
      elimination), adverse effects, and interactions (e.g. drug-drug, drug-food and
      drug-disease).

PMID- 10935431
TI  - Clinicopathological studies on diffuse Lewy body disease.
AB  - With reports of dementia cases with numerous cortical Lewy bodies and our
      proposal that this be named 'diffuse Lewy body disease' (DLBD), this condition
      has received a great deal of attention, first in Japan and subsequently in Europe
      and North America. In the early 1990s, similar types of nomenclature were
      considered, and at the First International Workshop in 1995, it was proposed that
      'dementia with Lewy bodies' be used as a generic term for Lewy body dementia,
      including the DLBD form. We review our previous clinicopathological findings and
      describe our recent immunohistochemical studies on DLBD.

PMID- 10935430
TI  - Management of the infant born to an HIV-1 infected mother.

PMID- 10935429
TI  - Common culprits in childhood poisoning: epidemiology, treatment and parental
      advice for prevention.
AB  - Unintentional poisoning in children less than 6 years of age is a common
      occurrence. The majority of cases involve 1- and 2-year-old children who ingest
      nonpharmaceutical products. Although the clinical outcomes of these exposures is
      usually favourable, deaths do occur. In the US, the causes of death most commonly
      reported by the American Association of Poison Control Centers Toxic Exposure
      Surveillance System (AAPCC TESS) are carbon monoxide and adult formulations of
      iron. The exposures most commonly reported by the AAPCC TESS are
      cosmetic/personal care products (e.g. perfume, cologne and aftershave), household
      cleaning substances (e.g. bleach and alkaline corrosives) and analgesics [e.g.
      paracetamol (acetaminophen)]. Prevention is important and exposure to poisons
      should be considered a preventable childhood injury. The use of child-resistant
      packaging and the secure storage of household substances are the basis of
      preventing unintentional exposures. Parents and healthcare professionals need to
      be aware of what constitutes high risk exposure, as well as those exposures which
      are common but not serious. Poison prevention efforts should also address the
      appropriate role of the poison information centre.

PMID- 10935432
TI  - Cerebral amyloid angiopathy: an overview.
AB  - Cerebral amyloid angiopathy (CAA) is characterized by amyloid deposition in
      cortical and leptomeningeal vessels. Several cerebrovascular amyloid proteins
      (amyloid beta-protein (Abeta), cystatin C (ACys), prion protein (AScr),
      transthyretin (ATTR), gelsolin (AGel), and ABri (or A-WD)) have been identified,
      leading to the classification of several types of CAA. Sporadic CAA of Abeta type
      is commonly found in elderly individuals and patients with Alzheimer's disease.
      Cerebral amyloid angiopathy is an important cause of cerebrovascular disorders
      including lobar cerebral hemorrhage, leukoencephalopathy, and small cortical
      hemorrhage and infarction. We review the clinicopathological and molecular
      aspects of CAA and discuss the pathogenesis of CAA with future perspectives.

PMID- 10935433
TI  - P-ANCA-positive Wegener's granulomatosis presenting with hypertrophic
      pachymeningitis and multiple cranial neuropathies: case report and review of
      literature.
AB  - An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies
      is reported. A 53-year-old woman with paraplegia and various neurological signs
      which developed over a 2 year period was diagnosed as having an epidural mass
      with thickened dura mater extending from the lower cervical to the thoracic
      spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness
      of the right eye with various cranial nerve deficits were found to be caused by
      the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus.
      Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, but
      cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) was negative by enzyme
      linked immunosorbent assay. The partially removed epidural mass with
      hypertrophied dura mater and biopsy of the paranasal lesions showed chronic
      granulomatous inflammation with vasculitis. The remaining lesions resolved with
      steroid therapy with remarkable neurological improvement. The positive p-ANCA
      test, paranasal involvement, the report of a similar histopathological case and a
      review of the literature on granulomatous pachymeningitis suggest the presence of
      p-ANCA-positive Wegener's granulomatosis with central nervous system involvement
      characterized by hypertrophic pachymeningitis and/or multiple cranial
      neuropathies.

PMID- 10935434
TI  - Neuropathological heterogeneity in Alzheimer's disease: a study of 80 cases using
      principal components analysis.
AB  - Three hypotheses have been proposed to explain neuropathological heterogeneity in
      Alzheimer's disease (AD): the presence of distinct subtypes ('subtype
      hypothesis'), variation in the stage of the disease ('phase hypothesis') and
      variation in the origin and progression of the disease ('compensation
      hypothesis'). To test these hypotheses, variation in the distribution and
      severity of senile plaques (SP) and neurofibrillary tangles (NFT) was studied in
      80 cases of AD using principal components analysis (PCA). Principal components
      analysis using the cases as variables (Q-type analysis) suggested that individual
      differences between patients were continuously distributed rather than the cases
      being clustered into distinct subtypes. In addition, PCA using the abundances of
      SP and NFT as variables (R-type analysis) suggested that variations in the
      presence and abundance of lesions in the frontal and occipital lobes, the
      cingulate gyrus and the posterior parahippocampal gyrus were the most important
      sources of heterogeneity consistent with the presence of different stages of the
      disease. In addition, in a subgroup of patients, individual differences were
      related to apolipoprotein E (ApoE) genotype, the presence and severity of SP in
      the frontal and occipital cortex being significantly increased in patients
      expressing apolipoprotein (Apo)E allele epsilon4. It was concluded that some of
      the neuropathological heterogeneity in our AD cases may be consistent with the
      'phase hypothesis'. A major factor determining this variation in late-onset cases
      was ApoE genotype with accelerated rates of spread of the pathology in patients
      expressing allele epsilon4.

PMID- 10935435
TI  - Dural band pathology in syringomyelia with Chiari type I malformation.
AB  - Surgical material taken from the 'outer layer' of thickened dura mater (dural
      band) at the craniovertebral junction of eight cases of syringomyelia with Chiari
      type I malformation was histologically examined in comparison with four autopsy
      cases as controls. The dural band was thickened and there were increased numbers
      of collagen fibers which showed fiber splitting, hyalinous nodule, calcification
      and/or ossification. These changes were not observed in the four control cases.
      Thus, it is suggested that the thickening of the dura mater may be a causative
      factor of syringomyelia with Chiari type I malformation. In addition, the
      histology of the thickened dura mater suggests the condition may be a consequence
      of birth injury in these patients.

PMID- 10935436
TI  - Meningioangiomatosis with a predominant fibrocalcifying component.
AB  - A case of meningioangiomatosis, resected from the parietal lobe in a 31-year-old
      female is presented. Macroscopically, the lesion was composed of five calcified
      nodules embedded within hardened elastic tissue. Histologically, cortical and
      subcortical calcified masses were found surrounded by a palisade of spindle
      and/or oval cells. In adjacent nervous tissue many pathological microvessels were
      observed and some were ensheathed by a perivascular proliferation of spindle
      cells. Moreover, gliosis with Rosenthal fibers and prominent connective tissue
      elements were observed. Immunohistochemical analysis based on monoclonal
      antibodies was performed. The spindle cells both within the palisades and the
      perivascular proliferations were vimentin and usually epithelial membrane
      antigenpositive. The possible pathogenesis of meningioangiomatosis is discussed
      and the role of angiogenesis within this lesion emphasized.

PMID- 10935437
TI  - A case of sporadic Creutzfeldt-Jakob disease with both plaque and synaptic-type
      deposition of prion protein.
AB  - We report a Japanese case of sporadic Creutzfeldt-Jakob disease (CJD) with
      particular clinical course and neuropathological findings. A 74-year-old female
      exhibited parkinsonism and later, dementia, myoclonus as well as visual
      hallucinations, lacking periodic synchronous discharges in the
      electroencephalogram. The duration of her illness was 2 years, longer than
      typical CJD cases which average 8 months' duration. Gray matter was severely
      affected, the Ammon's horn and subicular cortex were well preserved and many kuru
      plaques were observed in the cerebellum using routine histological stainings.
      Immunohistochemistry for prion protein (PrP) using both formic acid and
      hydrolytic autoclaving pretreatment revealed numerous prion plaques throughout
      the brain together with intense synaptic-type deposition of PrPCJD (abnormal
      isoform of PrP) in all gray matter examined, particularly in the Ammon's horn and
      subicular cortex. The definite combination of these two types of stain has never
      been reported previously in Japan other than in Gerstmann-Straussler-Scheinker
      syndrome. Relative resistance of the Ammon's horn and subicular cortex to the
      PrPCJD deposition is also discussed.

PMID- 10935438
TI  - Lateral ventricular meningioma encapsulated by the dura-like membrane.
AB  - The first case of a ventricular meningioma that was encapsulated by the dura-like
      membrane is reported. Magnetic resonance imaging (MRI) showed a heterogeneous
      mass with a low intensity rim in the trigone of the right lateral ventricle of a
      63-year-old male. Histological examination revealed that the tumor was a
      transitional meningioma encapsulated by a thick dura-like membrane. Moreover,
      abundant clusters of the dura-like connective tissue existed in the tumor,
      indicating that both the dura-like capsule and the dura-like clusters in the
      tumor were created by the tumor cells.

PMID- 10935440
TI  - Clinical concept of frontotemporal dementia.
AB  - The clinical concept of frontotemporal dementia is reviewed by discussing its
      relationships to several related concepts. These include dementia of the frontal
      lobe type, slowly progressive aphasia without dementia or primary progressive
      aphasia, semantic dementia and frontotemporal lobar degeneration. A number of
      examples of confusion in the terminology are also examined.

PMID- 10935439
TI  - Primary leiomyosarcoma of the cervical spine causing spontaneous compression
      fracture: report of an autopsy case.
AB  - An extremely rare case of the primary leiomyosarcoma of the cervical spine
      presenting as a compression fracture is reported. A 69-year-old man complained of
      dysesthesia of both hands. A plain radiograph, computed tomography and magnetic
      resonance imaging of the cervical spine showed a compression fracture of the
      vertebral body at C7 without the formation of an obvious mass. From radiological
      findings, the fracture was considered to be caused by an infiltrative vertebral
      bone tumor. Biopsy of the tumor revealed a leiomyosarcoma, a metastatic tumor
      being ruled out by a systemic investigation. The patient died of pleural
      metastasis 6 months later, and an autopsy confirmed the primary site of the tumor
      as the cervical spine.

PMID- 10935441
TI  - Frontotemporal dementia with motor neuron disease (amyotrophic lateral sclerosis
      with dementia).
AB  - Frontotemporal dementia (FTD) with motor neuron disease means amyotrophic lateral
      sclerosis (ALS) with dementia. In the cerebrum of this condition, the medial
      cortex of the rostral temporal lobe is constantly and most remarkably involved.
      Another constant and quite characteristic lesion is neuronal loss localized to
      the CA1-subiculum transitional area at the level of the pes hippocampi. The
      rostral portion of the parahippocampal gyrus, and the amygdaloid nucleus are also
      involved. Ubiquitinated intracytoplasmic inclusions are seen in the dentate
      granule cells and parahippocampal gyrus neurons. Some cases of ALS without
      dementia show the identical temporal lobe degeneration as well as the cortical
      ubiquitinated inclusions, thus raising the possibility of overlooked dementia or
      premature death of the patients. Similarly, recently proposed motor neuron
      disease-inclusion dementia may be a forme fruste of ALS with dementia.

PMID- 10935443
TI  - Introduction to symposium: intracranial dissecting aneurysms.

PMID- 10935442
TI  - Neuropathological discrepancy between Japanese Pick's disease without Pick bodies
      and frontal lobe degeneration type of frontotemporal dementia proposed by Lund
      and Manchester Group.
AB  - The concept of frontotemporal dementia (FTD) proposed by the Lund and Manchester
      group is useful because it distinguishes dementia with frontal and anterior
      temporal involvement from Alzheimer-type dementia. The classification and
      definition of FTD and related disorders, however, are controversial. One point of
      controversy is the neuropathology of the frontal lobe degeneration (FLD) type of
      FTD. The FLD type is described as having mild frontal and anterior temporal
      atrophy and no accompanying tau or ubiquitin pathology. We investigated cases of
      Japanese Pick's disease without Pick bodies (PB), the majority of which are
      thought to correspond to FLD type, in order to clarify whether the nature of the
      degeneration in these cases could be distinguishable from that in Japanese Pick's
      disease with PB, which corresponds approximately to the Pick type of the Lund and
      Manchester group. Except for the presence of tau-pathology, no obvious
      differences were noted between Pick's disease without PB (FLD type) and Pick's
      disease with PB (Pick type) either on neuropathological examination of own cases
      or a questionnaire survey of Japanese neuropathologists. The reason for this
      discrepancy may be based on the role of heredity, namely, most Japanese cases of
      Pick's disease are solitary, while the FTD cases of the Lund and Manchester group
      were reportedly accompanied by extensive familial history. There is a possibility
      that Japanese, British, and Swedish neuropathologists deal with heterogeneous
      groups of dementia characterized as FTD without tau or ubiquitin pathology.

PMID- 10935444
TI  - Clinical picture of intracranial non-traumatic dissecting aneurysm.
AB  - Non-traumatic intracranial arterial dissection has been accepted as a unique
      entity of 'cerebral infarction in otherwise healthy young adults', and is
      particularly prevalent in Western countries. A recent data collection and
      analysis have revealed additional clinical features. The nationwide study in
      Japan conducted in 1996 has provided new information on the natural history and
      current treatment of intracranial dissecting aneurysms in Japan. The incidence of
      symptomatic dissection was found to be much higher in the vertebrobasilar system
      than in the carotid system. The mean age of the patients was 51.3 years. Patients
      with carotid lesions were younger (mean 43.8 years). The male/female ratio was 2:
      1. Fifty-eight percent of patients presented with subarachnoid hemorrhage.
      Recurrence was more frequent in patients with subarachnoid hemorrhage (14%) than
      in patients with no hemorrhage (4.2%). Common radiological findings were
      dilatation, 'pearl and string' sign and narrowing of the affected artery.
      Surgical treatment involved a variety of procedures including proximal occlusion,
      entrapment, wrapping and endovascular embolization. Patients with subarachnoid
      hemorrhage (61%) underwent surgical treatment more frequently than patients with
      no hemorrhage (17%). Good recovery was achieved in 64% of all patients. Outcome
      was better in patients with no subarachnoid hemorrhage compared with those with
      hemorrhage.

PMID- 10935445
TI  - Clinicopathological features of non-atherosclerotic cerebral arterial trunk
      aneurysms.
AB  - Internal elastic lamina (IEL) is the most vital structure of the cerebral
      arterial wall. Longstanding weakness of the IEL due to hemodynamic stress is
      compensated by adaptive intimal thickening. Formation of cerebral arterial trunk
      aneurysm is assumed to be the result of a break in the equilibrium between
      hemodynamic stress and the condition of the IEL and intima. Cerebral arterial
      trunk aneurysms unrelated to the branching zones have several lesional patterns
      of IEL and the state of intima. There is a strong relationship between the
      pathological features of aneurysms and their clinical courses. We attempt to
      delineate the concept of cerebral arterial trunk aneurysms including 'dissecting
      aneurysms' and 'fusiform aneurysms'.

PMID- 10935446
TI  - Pathology of the arteries in the central nervous system with special reference to
      their dilatation: blood flow.
AB  - Arteries that belong to the central nervous system (CNS) have thick and
      monotonous internal elastic lamina (IEL), Willis ring, and no collateral branch
      to the systemic circulation. These characteristics suggest that the circulation
      of the CNS is constant. In order to know how flow controls the arterial
      configuration of the CNS, flow of the vertebral and basilar arteries was
      increased experimentally using eight adult male Japanese white rabbits. Flow
      increase was induced by the simple ligation of the bilateral common carotid
      arteries (ligation group, n = 4) or by the ligation of the bilateral common
      carotid arteries at 1 week after arteriovenous fistula (AVF) between the left
      common carotid artery and the left external jugular vein (ligation plus AVF
      group, n = 4). Cineangiography revealed distinct flow increase in the ligation
      group at 5 weeks after ligation and in the ligation plus AVF group at 5 weeks
      after AVF (4 weeks after ligation). Vertebral and basilar arteries were
      remarkably dilated and elongated. Histopathologically, severe disruption of the
      IEL and focal thinning of the media were distinct. Endothelial cells were
      preserved and there was no inflammatory cell infiltration. These morphological
      features are consistent with increased flow-induced adaptive remodeling. It is
      suggested that the constancy of the flow may give the arterial tree of the CNS
      these morphological characterizations.

PMID- 10935447
TI  - Pathology of a dissecting intracranial aneurysm.
AB  - The pathological findings of six autopsy cases of dissecting intracranial
      aneurysm are studied. Clinically, all cases exhibited systemic hypertension or
      left ventricular hypertrophy. Macroscopically, all cases exhibited rupture of the
      vertebral artery and subarachnoid hemorrhage. Two types of lesion were present.
      First, all cases showed the formation of a dilatated pseudoaneurysm with
      widespread disruption of the entire arterial wall, which was composed of thin
      adventitia. Second, a medial disruption of the arterial wall and subadventitial
      dissecting hemorrhage, which formed a false lumen and stenosis of the 'true'
      lumen of the artery, was also found. However, these lesions were found to be
      connected to the site of rupture. The autopsy cases within 1 day of onset of
      intracranial dissecting aneurysm showed the formation of fibrin thrombus, a
      marked degree of leukocyte infiltration and necrosis of the arterial wall at the
      site of the lesion. The cases that survived more than 1 week showed smooth muscle
      cell proliferation, macrophage accumulation and lymphocytic infiltration. No
      arteriosclerosis was found in any lesion studied. These data suggest that the
      disruption of the entire arterial wall might initially occur and cause medial
      disruption and subadventitial hemorrhage. Hypertension and arteriosclerosis might
      function as causal and protective factors in the pathogenesis of dissecting
      intracranial aneurysms, respectively.

PMID- 10935449
TI  - Immunohistochemical studies of the PrP(CJD) deposition in Creutzfeldt-Jakob
      disease.
AB  - The PrP(CJD) deposition in eight brains of sporadic Creutzfeldt-Jakob disease
      (CJD) was examined immunohistochemically using both hydrolytic autoclaving and
      formic acid pretreatment in order to understand the pathogenesis of CJD. Synaptic
      type PrP immunoreactivity was revealed in the gray matter in all cases and had a
      tendency to be weaker in devastated areas in cases with a longer duration of
      illness. However, in one particular case with numerous prion plaques, the
      degeneration was relatively mild while PrP(CJD) immunoreactivity was intense
      despite the longest duration of illness among the examined cases. Deep layer
      accentuation of PrP(CJD) immunoreactivity was observed in the cerebral cortices
      in most cases. This staining pattern, however, disappeared in a burnt-out lesion
      exhibiting status spongiosus. The granular layer was damaged mostly in the
      cerebellum of the advanced cases. PrP(CJD) and synaptophysin immunoreactivities
      decreased as the tissue degeneration progressed. Interestingly, the Purkinje
      cells had no positivity for PrP(CJD) in all cases, although the neurons in
      relatively preserved cerebellum showed apparent positivity for synaptophysin. In
      the Ammon's horn and subiculum the neurons were well preserved despite the marked
      immunoreactivity for PrP(CJD) in all cases, although some cases demonstrated
      severe spongiform change. Approximately half of the cases showed intracytoplasmic
      inclusion body-like immunoreactivity for PrP(CJD) in neurons of the dentate
      nucleus. These findings suggest that PrP(CJD) deposition may be an event that
      precedes neuronal degeneration evolving from deeper layers of the cerebral
      cortex. Although the Ammon's horn and subiculum showed striking PrP(CJD)
      deposition and spongiform change, neuronal loss did not take place, suggesting
      that deposited PrP(CJD) itself seems not to be directly harmful to the neurons.
      Some investigators have assumed that microglia activated by PrP(CJD) plays an
      important role in neuronal degeneration. Considering this, we speculate that
      microglia in the Ammon's horn and subiculum may have a unique characteristic of
      not responding to PrP(CJD).

PMID- 10935448
TI  - Beta-catenin expression in human neural cell lines following exposure to
      cytokines and growth factors.
AB  - Beta-catenin acts as a key mediator of the Wnt/Wingless signaling pathway
      involved in cell proliferation, differentiation and survival. Recent studies have
      shown that an unstable interaction between beta-catenin and the mutant presenilin
      1 induces neuronal apoptosis, and that beta-catenin levels are decreased in the
      brains of patients with Alzheimer's disease (AD). Since activated microglia and
      astrocytes play a role in the process of neuronal degeneration in AD, the
      cytokine/growth factor-regulated expression of beta-catenin in human neural cell
      lines, including NTera2 teratocarcinoma-derived differentiated neurons (NTera2
      N), IMR-32 neuroblastoma, SKN-SH neuroblastoma and U-373MG astrocytoma, was
      studied quantitatively following exposure to epidermal growth factor (EGF), basic
      fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, interferon (IFN)
      gamma, transforming growth factor (TGF)-beta1, dibutyryl cyclic adenosine 3',5'
      cyclic monophosphate (cAMP) (dbcAMP) or phorbol 12-myristate 13-acetate (PMA).
      Beta-catenin mRNA expressed constitutively in all of these cell lines was
      unaffected by treatment with any factors examined. In contrast, beta-catenin
      protein levels were reduced markedly in NTera2-N cells by exposure to dbcAMP, EGF
      or bFGF, and in U-373MG cells by treatment with dbcAMP or PMA, but were
      unaffected in any cell lines by BDNF, TNF-alpha, IL-1beta, IL-6, IFN-gamma or TGF
      beta1. These results indicate that beta-catenin is expressed constitutively in
      human neural cells and downregulated at a protein level by a set of growth
      factors in a cell type-specific manner.

PMID- 10935450
TI  - Effects of macrophage-colony-stimulating factor deficiency on the maturation of
      microglia and brain macrophages and on their expression of scavenger receptor.
AB  - Macrophage-colony-stimulating factor (M-CSF) regulates the survival,
      proliferation and differentiation of the mononuclear phagocyte lineage.
      Osteopetrotic (op/op) mice defective in producing functional M-CSF were used in
      order to investigate the role of M-CSF on the development of microglia and brain
      macrophages and the expression of scavenger receptor (SR). Adult op/op and
      littermate mice at 10-47 weeks of age were investigated by immunohistochemistry
      with a panel of monoclonal antibodies (F4/80, Mac-1, anti-major
      histocompatibility complex (MHC) class II and anti-SR), electron microscopy and
      reverse transcriptase-polymerase chain reaction (RT-PCR). Microglia were weakly
      immunolabeled with F4/80 and Mac-1 in op/op and littermate mice, but the number
      of microglia in op/op mice was reduced in the cerebrum, cerebellum and brainstem
      compared with that of normal littermates. The numbers of Mac-1-positive microglia
      in op/op mice was 39% (pons) and 30% (cerebellar cortex) lower than that in
      normal littermates (P<0.05). In addition, the microglia cell processes in op/op
      mice were often shorter than those in control mice. In op/op and littermate mice,
      both MHC class II and SR were present in perivascular cells and macrophages of
      the leptomeninx and choroid plexus. Ultrastructurally, perivascular cells
      appeared to be immature, since their cytoplasm was narrow and contained few
      inclusion bodies compared with those of control mice. Reverse transcriptase
      polymerase chain reaction showed a weak expression for SR mRNA in the brains of
      op/op mice as well as littermate mice. These results indicate that microglia are
      partly dependent on M-CSF for their proliferation and differentiation and that M
      CSF has no significant effect on the expression of SR in the physiological brain.
      The study also suggests that M-CSF affects the maturation of perivascular cells
      at the ultrastructural level.

PMID- 10935451
TI  - An autopsy case of postencephalitic parkinsonism of von Economo type: some new
      observations concerning neurofibrillary tangles and astrocytic tangles.
AB  - An autopsied case of postencephalitic parkinsonism of von Economo type with a 71
      year duration is reported. Several cases of postencephalitic parkinsonism of von
      Economo type have been reported in Japan but this is the first reported case from
      western Japan. The patient was a Japanese man who was 74 years of age at the time
      of death. He developed encephalitis of unknown etiology at the age of 3 years.
      The first symptom was antisocial behavior, which developed at 30 years of age. At
      the age of 40 years, the patient showed progressive parkinsonism.
      Neuropathological findings disclosed marked neuronal loss with gliosis in the
      substantia nigra, locus ceruleus, and raphe nuclei, as well as the appearance of
      neurofibrillary tangles in the aforementioned areas. There were also widespread
      tuft-shaped astrocytes (Tu-SA) in the central nervous system, including the
      thalamus. Tuft-shaped astrocytes are considered to represent non-reactive
      astrocytes because the distributions of neurofibrillary tangles (NFT) and Tu-SA
      are clearly different. Therefore, the primary astrocytic lesions in
      postencephalitic parkinsonism of von Economo type may be more widespread.
      Ultrastructurally, the Tu-SA consisted of straight filaments, 15 nm in width,
      which formed tight bundles. Ultrastructurally, NFF in this case revealed paired
      helical filaments but straight filaments, 15 nm in width, which were also found
      in the neurons of the substantia nigra.

PMID- 10935452
TI  - A learning rule for dynamic recruitment and decorrelation.
AB  - The interest in neuronal networks originates for a good part in the option not to
      construct, but to train them. The mechanisms governing synaptic modifications
      during such training are assumed to depend on signals locally available at the
      synapses. In contrast, the performance of a network is suitably measured on a
      global scale. Here we propose a learning rule that addresses this conflict. It is
      inspired by recent physiological experiments and exploits the interaction of
      inhibitory input and backpropagating action potentials in pyramidal neurons. This
      mechanism makes information on the global scale available as a local signal. As a
      result, several desirable features can be combined: the learning rule allows fast
      synaptic modifications approaching one-shot learning. Nevertheless, it leads to
      stable representations during ongoing learning. Furthermore, the response
      properties of the neurons are not globally correlated, but cover the whole
      stimulus space.

PMID- 10935453
TI  - A proposed name for aperiodic brain activity: stochastic chaos.

PMID- 10935454
TI  - Neural networks are useful tools for drug design.
AB  - A profound understanding of molecular recognition processes and the underlying
      molecular interaction patterns is a prerequisite for future progress and success
      in rational drug design. Neural networks could play an important role in guiding
      the Drug Discovery process through the extraction of relevant molecular features.

PMID- 10935455
TI  - How good are support vector machines?
AB  - Support vector (SV) machines are useful tools to classify populations
      characterized by abrupt decreases in density functions. At least for one class of
      Gaussian data model the SV classifier is not an optimal one according to a mean
      generalization error criterion. In real world problems, we have neither Gaussian
      populations nor data with sharp linear boundaries. Thus, the SV (maximal margin)
      classifiers can lose against other methods where more than a fixed number of
      supporting vectors contribute in determining the final weights of the
      classification and prediction rules. A good alternative to the linear SV machine
      is a specially trained and optimally stopped SLP in a transformed feature space
      obtained after decorrelating and scaling the multivariate data.

PMID- 10935456
TI  - Anxiety-like behavior in rats: a computational model.
AB  - This work describes a neural network model of the rat exploratory behavior in the
      elevated plus-maze, a test used to study anxiety. It involves three parameters:
      drive to explore; drive to avoid aversive stimuli; and spontaneous locomotor
      activity. Each network unit corresponds to a specific location in the maze and
      the connections, only between closest neighbors, represent the possible adjacent
      places to which a virtual rat can navigate. Competitive learning is used to
      generate a sequence of network states that correspond to the virtual rat
      successive locations in the maze. To evaluate the generality of the model it was
      also tested for two modifications of the elevated plus-maze: one with totally
      closed arms and the other with totally open arms. The results are compared with
      data obtained with rats. The simulations are consistent with experimental
      evidence and may provide an efficient way of describing the anxiety-like rat
      behavior in the elevated plus-maze. This could be useful for researching the
      emotional parameters involved in this anxiety animal model.

PMID- 10935457
TI  - Self-organization of orientation maps in a formal neuron model using a cluster
      learning rule.
AB  - Self-organization of orientation maps due to external stimuli in the primary
      visual area of the cerebral cortex is studied in a two-layered neural network
      which consists of formal neuron models with a sigmoidal output function. A
      cluster learning rule is proposed as an extended Hebbian learning rule, where a
      modification of synaptic connections is influenced by an activation of
      neighboring output neurons. By making use of self-consistent Monte Carlo method,
      we evaluate output responses of neurons against explicit inputs after the
      learning. An orientation map calculated from the output responses reproduces
      characteristic features of biological ones. Moreover quantitative analysis of our
      results are consistent with those of experimental results. It is shown that the
      cluster learning rule plays an important role in forming smooth changes of
      preferred orientations.

PMID- 10935459
TI  - Cascade associative memory storing hierarchically correlated patterns with
      various correlations.
AB  - In conventional models for storing hierarchically correlated patterns,
      correlations between ancestors (first-level patterns) and their descendants
      (second-level ones) are assumed to be uniform, so that the descendants are
      distributed around their ancestors with equal distances. However, this assumption
      might be unnatural. We believe that objects are encoded into patterns by
      preserving the similarity between them. In this case, descendants are distributed
      around their ancestors with various distances, so that the assumption is invalid
      and the conventional models become inapplicable. To overcome this, we propose a
      model CASM3 for storing hierarchically correlated patterns with various
      correlations. In CASM3, critical load levels vary with the descendants, and
      become higher with increasing correlations. Increase in load level successively
      destroys the memories of the descendants in descending order of their
      correlations. The size of the basins of attraction depends on the range of the
      correlations, and becomes larger as the correlation range is shifted toward lower
      levels.

PMID- 10935458
TI  - A cascade associative memory model with a hierarchical memory structure.
AB  - The introduction of a hierarchical memory structure into a cascade associative
      memory model for storing hierarchically correlated patterns improves the storage
      capacity and the size of the basins of attraction remarkably. A learning
      algorithm groups descendants (second-level patterns) according to their ancestors
      (first-level ones), and organizes the memory structure in a weight matrix where
      the groups are memorized separately. The weight matrix is, thus, in the form of a
      pile of covariance matrices, each of which is responsible for recalling only the
      descendants of each ancestor. Putting it simply, the model is multiplex
      associative memory. The recalling process proceeds as follows: the model first
      recalls the ancestor of a target descendant. Then, the dynamics with dynamic
      threshold combines the ancestor and the weight matrix to activate the covariance
      matrix for recalling only the descendants of the ancestor. This mechanism
      suppresses the cross-talk noise generated by the descendants of the other
      ancestors, and the recalling ability is enhanced.

PMID- 10935460
TI  - On impulsive autoassociative neural networks.
AB  - Many systems existing in physics, chemistry, biology, engineering, and
      information science can be characterized by impulsive dynamics caused by abrupt
      jumps at certain instants during the process. These complex dynamical behaviors
      can be modeled by impulsive differential systems or impulsive neural networks.
      This paper formulates and studies a new model of impulsive autoassociative neural
      networks. Several fundamental issues, such as global exponential stability and
      existence and uniqueness of equilibria of such neural networks, are established.

PMID- 10935461
TI  - Pattern segmentation in a binary/analog world: unsupervised learning versus
      memory storing.
AB  - We discuss the problem of segmentation in pattern recognition. We adopt the model
      and the general approach in the landmark paper by Wang, Buhmann and von der
      Malsburg (Neural Computation, (1990), 2, 94-106), and expand their model in a
      number of ways. We review their solution to the segmentation problem in
      associative memory, which consists in feature binding being expressed by
      synchrony relations between oscillators or populations of neurons. We extend the
      model by introducing a law of synaptic change, which allows the network to learn
      by structuring itself in response to stimuli with relevant features. We discuss
      the problem of interference between pattern completion and the learning of new
      memories. We also propose a form of multiplexing of input information taking
      advantage of the time-structure of the neurons' response. It is based on the
      assessment of analog as well as of binary properties of the stimuli and provides
      for an enhancement of the network's processing capacity. The relevance of the
      results for biological systems is pointed out.

PMID- 10935462
TI  - Partially pre-calculated weights for the backpropagation learning regime and high
      accuracy function mapping using continuous input RAM-based sigma-pi nets.
AB  - In this article we present a methodology that partially pre-calculates the weight
      updates of the backpropagation learning regime and obtains high accuracy function
      mapping. The paper shows how to implement neural units in a digital formulation
      which enables the weights to be quantised to 8-bits and the activations to 9
      bits. A novel methodology is introduced to enable the accuracy of sigma-pi units
      to be increased by expanding their internal state space. We, also, introduce a
      novel means of implementing bit-streams in ring memories instead of utilising
      shift registers. The investigation utilises digital "Higher Order" sigma-pi nodes
      and studies continuous input RAM-based sigma-pi units. The units are trained with
      the backpropagation learning regime to learn functions to a high accuracy. The
      neural model is the sigma-pi units which can be implemented in digital
      microelectronic technology. The ability to perform tasks that require the input
      of real-valued information, is one of the central requirements of any cognitive
      system that utilises artificial neural network methodologies. In this article we
      present recent research which investigates a technique that can be used for
      mapping accurate real-valued functions to RAM-nets. One of our goals was to
      achieve accuracies of better than 1% for target output functions in the range Y
      epsilon [0,1], this is equivalent to an average Mean Square Error (MSE) over all
      training vectors of 0.0001 or an error modulus of 0.01. We present a development
      of the sigma-pi node which enables the provision of high accuracy outputs. The
      sigma-pi neural model was initially developed by Gurney (Learning in nets of
      structured hypercubes. PhD Thesis, Department of Electrical Engineering, Brunel
      University, Middlessex, UK, 1989; available as Technical Memo CN/R/144). Gurney's
      neuron models, the Time Integration Node (TIN), utilises an activation that was
      derived from a bit-stream. In this article we present a new methodology for
      storing sigma-pi node's activations as single values which are averages. In the
      course of the article we state what we define as a real number; how we represent
      real numbers and input of continuous values in our neural system. We show how to
      utilise the bounded quantised site-values (weights) of sigma-pi nodes to make
      training of these neurocomputing systems simple, using pre-calculated look-up
      tables to train the nets. In order to meet our accuracy goal, we introduce a
      means of increasing the bandwidth capability of sigma-pi units by expanding their
      internal state-space. In our implementation we utilise bit-streams when we
      calculate the real-valued outputs of the net. To simplify the hardware
      implementation of bit-streams we present a method of mapping them to RAM-based
      hardware using 'ring memories'. Finally, we study the sigma-pi units' ability to
      generalise once they are trained to map real-valued, high accuracy, continuous
      functions. We use sigma-pi units as they have been shown to have shorter training
      times than their analogue counterparts and can also overcome some of the
      drawbacks of semi-linear units (Gurney, 1992. Neural Networks, 5, 289-303).

PMID- 10935463
TI  - Neural net based MRAC for a class of nonlinear plants.
AB  - A neural net based state feedback model reference adaptive control scheme is
      presented for a class of nonlinear plants. The proposed scheme employs a time
      varying pseudo-linear state feedback control, where the state feedback gain being
      generated from the output of artificial neural networks. The plant need not be in
      a feedback linearizable form. Both regulation and tracking control have been
      considered. Global stability of the scheme has been proved through Lyapunov
      theory. The extension of the scheme to MIMO plants is also included. Simulation
      studies have been conducted on an industrial robot to validate and illustrate the
      proposed method.

PMID- 10935464
TI  - Training neural networks to be insensitive to weight random variations.
AB  - Neural network weights are subject to errors caused by technological tolerances
      when implemented in digital or analog hardware. Since these random variations are
      unavoidable and unpredictable, they can seriously affect the expected
      performances. This work proposes a learning algorithm that takes weight
      tolerances into account and guarantees a low sensitivity to them. Some
      experimental results show the validity of the suggested approach.

PMID- 10935465
TI  - The apoptosome: heart and soul of the cell death machine.
AB  - Apoptosis is a fundamental biologic process by which metazoan cells orchestrate
      their own self-demise. Genetic analyses of the nematode C elegans identified
      three core components of the suicide apparatus which include CED-3, CED-4, and
      CED-9. An analogous set of core constituents exists in mammalian cells and
      includes caspase-9, Apaf-1, and bcl-2/xL, respectively. CED-3 and CED-4, along
      with their mammalian counterparts, function to kill cells, whereas CED-9 and its
      mammalian equivalents protect cells from death. These central components
      biochemically intermingle in a ternary complex recently dubbed the "apoptosome."
      The C elegans protein EGL-1 and its mammalian counterparts, pro-apoptotic members
      of the bcl-2 family, induce cell death by disrupting apoptosome interactions.
      Thus, EGL-1 may represent a primordial signal integrator for the apoptosome.
      Various biochemical processes including oligomerization, adenosine triphosphate
      ATP/dATP binding, and cytochrome c interaction play a role in regulating the
      ternary death complex. Recent studies suggest that cell death receptors, such as
      CD95, may amplify their suicide signal by activating the apoptosome. These mutual
      associations by core components of the suicide apparatus provide a molecular
      framework in which diverse death signals likely interface. Understanding the
      apoptosome and its cellular connections will facilitate the design of novel
      therapeutic strategies for cancer and other disease states in which apoptosis
      plays a pivotal role.

PMID- 10935466
TI  - Construction of a high-resolution physical map of the approximate 1-Mb region of
      human chromosome 7q31.1-q31.2 harboring a putative tumor suppressor gene.
AB  - Reports of frequent loss of heterozygosity (LOH) of markers on human chromosome
      7q in malignant myeloid disorders as well as breast, prostate, ovarian, colon,
      head and neck, gastric, pancreatic, and renal cell carcinomas suggest the
      presence of a tumor suppressor gene (TSG). Functional assays have demonstrated
      that the introduction of an intact copy of human chromosome 7 (hchr7) can restore
      senescence to immortalized human fibroblast cell lines having LOH of markers
      within 7q31-q32 and can inhibit the tumorigenic phenotype of a murine squamous
      cell carcinoma cell line. To facilitate the cloning of the putative TSG, we have
      constructed a high-resolution physical map of this region of hchr7, specifically
      that encompassing the markers D7S522 and D7S677 within 7q31.1-q31.2. By using a
      lower resolution yeast artificial chromosome-based map as a starting framework,
      we established complete clone coverage of the implicated critical region in
      bacterial-artificial chromosomes (BACs) and P1-derived artificial chromosomes
      (PACs). The resulting BAC/PAC-based contig map has provided suitable clones for
      the systematic sequencing of the entire interval. In addition, we have already
      identified 29 clusters of overlapping expressed-sequence tags (ESTs) and 4 known
      genes contained within these clones. Together, the physical map reported here
      coupled with the evolving sequence and gene maps should hasten the identification
      of the putative TSG residing within this region of hchr7.

PMID- 10935467
TI  - Collateral expression of proangiogenic and tumorigenic properties in intestinal
      epithelial cell variants selected for resistance to anoikis.
AB  - Although in vitro anchorage-independent growth is widely used as a marker of cell
      transformation, the biological implications of this trait are poorly understood.
      We previously demonstrated that enforced anchorage-independent growth of a
      nontumorigenic, immortalized epithelial cell line (IEC-18) in multicellular
      spheroid culture results in massive apoptotic cell death. This death process,
      termed anoikis, is prevented by expression of transforming oncogenes, which also
      confer tumorigenic competence. This study examines whether acquisition of an
      anoikis-resistant phenotype is causally related to the tumorigenic capacity of
      transformed epithelial cells. Parental IEC-18 cells were subjected to 10 cycles
      of selection for survival in speroid culture. Unlike parental cells, the
      resulting anoikis-resistant variants (AR1.10 and AR2.10) formed relatively large
      tumors in nude mice. Both anoikis-resistant sublines displayed upregulated
      expression of vascular endothelial growth factor (VEGF), a potent angiogenesis
      stimulator. VEGF121 overexpression alone did not induce tumorigenic conversion of
      parental IEC-18 cells, which remained highly susceptible to anoikis. We postulate
      that both anoikis-resistance and angiogenic-competence contribute to tumor
      formation. Development of anoikis-resistance can be then viewed as a precondition
      for expression of the tumorigenic phenotype. Our results suggest that even when
      angiogenesis is not a rate limiting factor (e.g. in vitro) the selective
      pressures of solid tumor-like, 3-dimensional growth conditions favoring anoikis
      resistance result in collateral induction of a proangiogenic phenotype.

PMID- 10935468
TI  - Inhibition of tumor growth, angiogenesis, and microcirculation by the novel Flk-1
      inhibitor SU5416 as assessed by intravital multi-fluorescence videomicroscopy.
AB  - Vascular endothelial growth factor (VEGF) plays a fundamental role in mediating
      tumor angiogenesis and tumor growth. Here we investigate the direct effect of a
      novel small molecule inhibitor of the Flk-1-mediated signal transduction pathway
      of VEGF, SU5416, on tumor angiogenesis and microhemodynamics of an experimental
      glioblastoma by using intravital multifluorescence videomicroscopy. SU5416
      treatment significantly suppressed tumor growth. In parallel, SU5416 demonstrated
      a potent antiangiogenic activity, resulting in a significant reduction of both
      the total and functional vascular density of the tumor microvasculature, which
      indicates an impaired vascularization as well as significant perfusion failure in
      treated tumors. This malperfusion was not compensated for by changes in vessel
      diameter or recruitment of nonperfused vessels. Analyses of the tumor
      microcirculation revealed significant microhemodynamic changes after angiogenesis
      blockage such as a higher red blood cell velocity and blood flow in remnant tumor
      vessels when compared with controls. Our results demonstrate that the novel
      antiangiogenic concept of targeting the tyrosine kinase of Flk-1/KDR by means of
      a small molecule inhibitor represents an efficient strategy to control growth and
      progression of angiogenesis-dependent tumors. This study provides insight into
      microvascular consequences of Flk-1/KDR targeting in vivo and may have important
      implications for the future treatment of angiogenesis-dependent neoplasms.

PMID- 10935469
TI  - Progressive increase in telomerase activity from benign melanocytic conditions to
      malignant melanoma.
AB  - The expression of telomerase activity and the in situ localization of the human
      telomerase RNA component (hTR) in melanocytic skin lesions was evaluated in
      specimens from sixty-three patients. Specimens of melanocytic nevi, primary
      melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight
      patients, whereas metastasized lymph nodes were obtained from five patients.
      Telomerase activity was determined in these specimens by using a Polymerase Chain
      Reaction-based assay (TRAP). High relative mean telomerase activity levels were
      detected in metastatic melanoma (subcutaneous metastases = 54.5, lymph node
      metastases = 56.5). Much lower levels were detected in primary melanomas, which
      increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark
      III = 1.1, and Clark IV = 1.9). Twenty-six formalin-fixed, paraffin-embedded
      melanocytic lesions were sectioned and analyzed for telomerase RNA with a
      radioactive in situ hybridization assay. In situ hybridization studies with a
      probe to the template RNA component of telomerase confirmed that expression was
      almost exclusively confined to tumor cells and not infiltrating lymphocytes.
      These results indicate that levels of telomerase activity and telomerase RNA in
      melanocytic lesions correlate well with clinical stage and could potentially
      assist in the diagnosis of borderline lesions.

PMID- 10935470
TI  - In vivo selection and characterization of metastatic variants from human
      pancreatic adenocarcinoma by using orthotopic implantation in nude mice.
AB  - We determined whether the implantation of human pancreatic cancer cells into the
      pancreas of nude mice can be used to select variants with increasing metastatic
      potential. COLO 357 line fast-growing cells were injected into the spleen or
      pancreas of nude mice. Hepatic metastases were harvested, and tumor cells were
      reinjected into the spleen or pancreas. This cycle was repeated several times to
      yield cell lines L3.6sl (spleen to liver) and L3.6pl (pancreas to liver). The
      variant cells produced significantly higher incidence and number of lymph node
      and liver metastases than the parental cells. Their increased metastatic
      potential was associated with increased expression (mRNA and protein) of the
      proangiogenic molecules basic fibroblast growth factor, vascular endothelial
      growth factor, and interleukin-8. The metastatic cells also exhibited increased
      motility and invasiveness, which were associated with increased expression of
      collagenase type IV (MMP-9) and decreased expression of E-cadherin. Collectively,
      the data show that the orthotopic implantation of human pancreatic cancer cells
      in nude mice is a relevant model with which to study the biology of pancreatic
      cancer metastasis and to select variant cell lines with enhanced metastatic
      potential.

PMID- 10935471
TI  - A caspase-resistant form of Bcl-X(L), but not wild type Bcl-X(L), promotes
      clonogenic survival after ionizing radiation.
AB  - Bcl-2 and Bcl-X(L) belong to a family of proteins overexpressed in a variety of
      human cancers which inhibit apoptosis in response to a number of stimuli
      including chemotherapeutic agents and ionizing radiation. To better understand
      the role of these polypeptides in modulating the response of cancer cells to
      ionizing radiation we used cell lines that were engineered to overexpress the two
      polypeptides. Although Bcl-2 and Bcl-X(L) overexpression resulted in inhibition
      of radiation-induced apoptosis, it did not result in enhanced clonogenic
      survival. Consistent with this was the observation that Bcl-2 and Bcl-X(L)
      protected cells from DNA fragmentation, loss of mitochondrial membrane potential,
      and caspase activation for up to 72 hours after irradiation. Beyond 72 hours,
      there was a rapid loss in the ability of Bcl-2 and Bcl-X(L) to inhibit these
      markers of apoptosis. When Bcl-X(L) was analyzed at 72 hours after irradiation
      and beyond, a rapid accumulation of a 16-kDa form of Bcl-X(L) was observed. To
      test the hypothesis that cleavage of the 29-kDa form of Bcl-X(L) by caspases to a
      16-kDa polypeptide results in its inability to inhibit apoptosis beyond 72 hours,
      we constructed a cell line that overexpressed a caspase-resistant form of Bcl
      X(L) (Bcl-X(L)-deltaloop). Cells overexpressing Bcl-X(L)-deltaloop were resistant
      to apoptosis beyond 72 hours after irradiation and did not contain the 16-kDa
      form at these time points. In addition, Bcl-X(L)-deltaloop overexpression
      resulted in enhanced clonogenic survival compared with control or Bcl-X(L)
      overexpressing cells. These results provide a molecular basis for the observation
      that expression of Bcl-2 or Bcl-X(L) is not a prognostic marker of tumor response
      to cancer therapy.

PMID- 10935472
TI  - Mutation and expression of the p51 gene in human lung cancer.
AB  - A newly identified gene, p51, is a functional and structural homologue of the p53
      gene and thus a Candidate tumor suppressor gene. To elucidate the role of the p51
      gene in lung carcinogenesis, we determined the sequences of exon-intron
      boundaries and the 5'- and 3'-flanking regions of all the 15 coding exons and
      performed a mutation analysis, as well as detailed analysis for gene expression.
      A frameshift mutation was detected in 1 of 44 lung cancer cell lines, whereas no
      mutation was detected in 45 primary lung cancers. Thus, p51 mutation occurs only
      in a small subset of lung cancer. Expression of the p51 gene was detected in 23
      of 43 cell lines by Northern blot analysis and 34 of 44 by reverse transcriptase
      polymerase chain reaction (RT-PCR) analysis. Thus, p51 expression is low or
      absent in a subset of lung cancer. The deltaN isotype of p51 transcripts was
      dominantly expressed in several cell lines, particularly in cell lines with high
      levels of p51 expression. Because the deltaN isotype encodes a protein that
      transdominantly suppresses the transactivation function of the TA type of p51, it
      is possible that p51 protein is not functionally active, even in lung cancer
      cells with p51 mRNA expression, due to expression of dominant-negative p51
      protein. These results suggested that the p51 gene is inactive in a considerable
      proportion of lung cancers. RT-PCR analysis also revealed the presence of a novel
      type of mRNA transcript, p51delta, which lacks exons 12 and 13 by alternative
      splicing. The delta isotype was expressed in 18 of 44 lung cancer cell lines and
      in diverse normal tissues. Further analysis on p51 expression in cancerous as
      well as noncancerous cells will provide us with valuable information for the
      understanding of multiple functions of the p53 family proteins in human
      carcinogenesis.

PMID- 10935473
TI  - Lack of homozygously inactivated p73 in single-copy MYCN primary neuroblastomas
      and neuroblastoma cell lines.
AB  - We examined 18 neuroblastoma cell lines and 32 primary single-copy MYCN tumor
      specimens to determine whether mutations of p73, a novel p53-related gene located
      in chromosome band 1p36.33, contribute to the genesis or progression of childhood
      neuroblastoma. By fluorescence in situ hybridization, 16 of the 18 cell lines,
      but only 3 of the 32 primary tumors, had evidence of a deleted p73 allele.
      Sequence analysis of the p73 coding region in the mRNAs expressed by these cell
      lines and tumors did not reveal inactivating mutations, suggesting that p73 is
      not homozygously inactivated in neuroblastoma. However, several novel splice
      forms of p73 mRNAs were identified, including one without exon 11 that
      predominated in multiple MYCN-amplified cell lines. Its encoded p73 protein
      differed from other splice forms in that the C-terminus was derived from an
      alternative reading frame. Further study of the functional properties of the
      protein encoded by this splice form of p73 will be needed to determine whether it
      contributes to the pathogenesis of childhood neuroblastoma with MYCN gene
      amplification.

PMID- 10935476
TI  - Loss of immunoreactivity for human calmodulin-like protein is an early event in
      breast cancer development.
AB  - Cell proliferation requires calmodulin, a protein that regulates calcium
      dependent enzymes involved in signal transduction pathways in eukaryotic cells.
      Calmodulin-like protein (CLP) is found in certain epithelial cell types,
      including normal breast epithelium, and, although it closely resembles calmodulin
      in amino acid sequence, CLP interacts with different proteins than does
      calmodulin. The observation that CLP mRNA expression is dramatically reduced in
      transformed breast epithelial cells led to two hypotheses: (1) CLP helps to
      maintain the differentiated state in epithelial cells; and (2) downregulation of
      CLP accompanies malignant transformation of breast epithelial cells. The
      objective of this study was to determine if the expression of CLP in human breast
      cancer specimens is reduced in comparison to its expression in normal breast
      tissue. Eighty human breast cancer biopsy specimens were analyzed
      immunohistochemically for CLP expression by using a polyclonal rabbit antihuman
      CLP antibody. CLP expression was reduced in 79% to 88% of the invasive ductal
      carcinoma and lobular carcinoma specimens and in a similar fraction of the ductal
      carcinoma in-situ specimens, compared with normal breast specimens. None of the
      breast cancer specimens showed an increase in CLP expression. These findings
      support the hypotheses that CLP behaves as a functional tumor suppressor protein
      and is downregulated early in breast cancer progression.

PMID- 10935474
TI  - Causes and effects of heterogeneous perfusion in tumors.
AB  - A characteristic of solid tumors is their heterogeneous distribution of blood
      flow, with significant hypoxia and acidity in low-flow regions. We review effects
      of heterogeneous tumor perfusion are reviewed and propose a conceptual model for
      its cause. Hypoxic-acidic regions are resistant to chemo- and radiotherapy and
      may stimulate progression to a more metastatic phenotype. In normal tissues,
      hypoxia and acidity induce angiogenesis, which is expected to improve perfusion.
      However, aggressive tumors can have high local microvessel density simultaneously
      with significant regions of hypoxia and acidosis. A possible explanation for this
      apparent contradiction is that the mechanisms regulating growth and adaptation of
      vascular networks are impaired. According to a recent theory for structural
      adaptation of vascular networks, four interrelated adaptive responses can work as
      a self-regulating system to produce a mature and efficient blood distribution
      system in normal tissues. It is proposed that heterogeneous perfusion in tumors
      may result from perturbation of this system. Angiogenesis may increase perfusion
      heterogeneity in tumors by increasing the disparity between parallel low- and
      high-resistance flow pathways. This conceptual model provides a basis for future
      rational therapies. For example, it indicates that selective destruction of tumor
      vasculature may increase perfusion efficiency and improve therapeutic efficacy.

PMID- 10935477
TI  - Dynamic remodeling of the vascular bed precedes tumor growth: MLS ovarian
      carcinoma spheroids implanted in nude mice.
AB  - The goal of this study was to monitor the vascular bed during the lag phase in
      growth of implanted spheroids as a model of tumor dormancy. Vascular development
      and tumor growth were followed up by magnetic resonance imaging in a model system
      of MLS ovarian carcinoma spheroids implanted subcutaneously in female nude mice.
      Apparent vessel density in a 1-mm rim surrounding the spheroid was evaluated by
      gradient echo imaging as a measure of the angiogenic potential of the tumor.
      Vascular functionality and maturation were assessed by signal intensity changes
      in response to hyperoxia (elevated oxygen) and hypercapnia (elevated carbon
      dioxide), respectively. Tumor growth was delayed by 12 to 57 days after
      implantation. During this long period in which tumor volume did not change, up to
      6 cycles of vascular development and regression were observed. We propose here
      that dynamic remodeling of the vascular bed may precede exit of tumors from
      dormancy. The sustained oscillations in the angiogenic response to the implanted
      spheroid are consistent with hypoxic regulation of vascular endothelial growth
      factor (VEGF), combined with the role of VEGF as an essential survival factor for
      newly formed blood vessels. Vascular maturation, manifested by physiological
      vasodilatory response to carbon dioxide, may be important for conferring vascular
      stability and exit from dormancy.

PMID- 10935475
TI  - "...those left behind." Biology and oncology of invasive glioma cells.
AB  - Although significant technical advances in surgical and radiation treatment for
      brain tumors have emerged in recent years, their impact on clinical outcome for
      patients has been disappointing. A fundamental source of the management challenge
      presented by glioma patients is the insidious propensity of the malignant cells
      to invade into adjacent normal brain. Invasive tumor cells escape surgical
      removal and geographically dodge lethal radiation exposure. Recent improved
      understanding of the biochemistry and molecular determinants of glioma cell
      invasion provide valuable insight to the underlying biological features of the
      disease, as well as illuminating possible new therapeutic targets. Heightened
      commitment to migrate and invade is accompanied by a glioma cell's reduced
      proliferative activity. The microenvironmental manipulations coincident to
      invasion and migration may also impact the glioma cell's response to cytotoxic
      treatments. These collateral aspects of the glioma cell invasive phenotype should
      be further explored and exploited as novel antiglioma therapies.

PMID- 10935479
TI  - Chromosomal and extrachromosomal instability of the cyclin D2 gene is induced by
      Myc overexpression.
AB  - We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic
      tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which
      characteristically contain Myc-activating chromosome translocations and
      constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin
      D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell
      lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2
      gene, detected by Southern blot, fluorescent in situ hybridization (FISH), and in
      extrachromosomal preparations (Hirt extracts). Cyclin D2 instability was not seen
      in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of
      c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera
      was activated in two mouse cell lines. After 3 to 4 days of Myc-ER activation,
      instability at the cyclin D2 locus was seen in the form of extrachromosomal
      elements, determined by FISH of metaphase and interphase nuclei and of purified
      extrachromosomal elements. At the same time points, Northern and Western blot
      analyses detected increased cyclin D2 mRNA and protein levels. These data suggest
      that Myc-induced genomic instability may contribute to neoplasia by increasing
      the levels of a cell cycle-regulating protein, cyclin D2, via intrachromosomal
      amplification of its gene or generation of extrachromosomal copies.

PMID- 10935478
TI  - Differentiation of human malignant melanoma cells that escape apoptosis after
      treatment with 9-nitrocamptothecin in vitro.
AB  - After in-vitro exposure to 0.05 micromol/L 9-nitrocamptothecin (9NC) for periods
      of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1B cells
      die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the
      cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume
      cell cycling or remain arrested depending on the duration of 9NC exposure. In
      contrast to cycling malignant cells, the cells irreversibly arrested at G2
      exhibit features of normal-like cells, the melanocytes, as assessed by the
      appearance of dendrite-like structures; loss of proliferative activity; synthesis
      of the characteristic pigment, melanin; and, particularly, loss of tumorigenic
      ability after xenografting in immunodeficient mice. Further, the expression of
      the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G2
      arrested, but downregulated in density G1-arrested cells, whereas the reverse is
      observed in the expression of another cyclin-dependent kinase inhibitor, p21.
      These results suggest that malignant melanoma SB1B cells that escape 9NC-induced
      death by apoptosis undergo differentiation toward nonmalignant, normal-like
      cells.

PMID- 10935481
TI  - Application of comparative genomic hybridization, spectral karyotyping, and
      microarray analysis in the identification of subtype-specific patterns of genomic
      changes in rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) in children occurs predominantly as two major
      histologically defined subtypes called embryonal RMS (RMS-E) and the
      prognostically less favorable alveolar RMS (RMS-A). Comparative genomic
      hybridization (CGH) was performed on 21 RMS and identified consistent gains
      affecting chromosomes 2 (8/10), 5 (5/10), 6 (3/10), 7 (7/10), 8 (9/10), 11 (6/
      10), and 12 (5/10) in RMS-E. Losses/deletions involved chromosomes 19 (2/10) and
      chromosomes 4, 9, 10, 17, 21 (1/10 each). High copy number amplification,
      involving the 2p24 region (5/11) and less frequently, the 12q13-21 (2/11), 9p22
      (1/11), and 17q22-25 (1/11) regions, was detected in RMS-A. Gene amplification at
      band 2p24 was present in 6/12 alveolar tumors, and in each case, MYCN was
      amplified, together with the distally placed DDX1 gene. For these patients there
      was a shorter disease free interval and a higher mortality than patients with
      tumors without amplification. Detailed spectral karyotype analysis (SKY) was
      performed on two RMS cell lines (one of each subtype) and identified a
      surprisingly high level of structural change. Gene expression studies with the
      Atlas Human Cancer Array (588 genes) showed that 153 genes generated a signal of
      similar intensity in both cell lines, and 45 genes appeared to have subtype
      specific expression. The chromosomal location of differentially expressed genes
      was compared to the pattern of genomic alteration in RMS as determined by CGH in
      this study and the literature.

PMID- 10935480
TI  - p27KIP1 deletions in childhood acute lymphoblastic leukemia.
AB  - The p27KIP1 gene, which encodes a cyclin-dependent kinase (CDK) inhibitor, has
      been assigned to chromosome band 12p12, a region often affected by
      cytogenetically apparent deletions or translocations in childhood acute
      lymphoblastic leukemia (ALL). As described here, fluorescence in situ
      hybridization (FISH) analysis of 35 primary ALL samples with cytogenetic evidence
      of 12p abnormalities revealed hemizygous deletions of p27KIP1 in 29 cases.
      Further analysis of 19 of these cases with two additional gene-specific probes
      from the 12p region (hematopoietic cell phosphatase, HCP and cyclin D2, CCND2)
      showed that p27KIP1 is located more proximally on the short arm of chromosome 12
      and is deleted more frequently than either HCP or CCND2. Of 16 of these cases
      with hemizygous deletion of p27KIP1, only eight showed loss of HCP or CCND2,
      whereas loss of either of the latter two loci was uniformly associated with loss
      of p27KIP1. Missense mutations or mutations leading to premature termination
      codons were not detected in the coding sequences of the retained p27KIP1 alleles
      in any of the 16 ALL cases examined, indicating a lack of homozygous
      inactivation. By Southern blot analysis, one case of primary T-cell ALL had
      hemizygous loss of a single p27KIP1 allele and a 34.5-kb deletion, including the
      second coding exon of the other allele. Despite homozygous inactivation of p27KP1
      in this case, our data suggest that haploinsufficiency for p27KIP1 is the primary
      consequence of 12p chromosomal deletions in childhood ALL. The oncogenic role of
      reduced, but not absent, levels of p27KIP1 is supported by recent studies in
      murine models and evidence that this protein not only inhibits the activity of
      complexes containing CDK2 and cyclin E, but also promotes the assembly and
      catalytic activity of CDK4 or CDK6 in complexes with cyclin D.

PMID- 10935482
TI  - Role for p53 in the recovery of transcription and protection against apoptosis
      induced by ultraviolet light.
AB  - We have previously suggested that the inhibition of RNA polymerase II-mediated
      transcription after exposure to UV light promotes the accumulation of p53 and the
      induction of apoptosis (Oncogene 13, 823-831). However, it was not clear whether
      p53 induction was contributing to apoptosis. Here we report that apoptosis is
      triggered at lower UV doses in p53-deficient Li-Fraumeni syndrome (LFS) and human
      papillomavirus (HPV) E6 expressing fibroblasts than in normal cells, suggesting
      that p53 can be protective against UV-induced apoptosis. There is no significant
      difference in the effect of UV-irradiation on the cell cycle distribution of
      normal and primary LFS fibroblasts. Importantly, the recovery of nascent mRNA
      synthesis in all p53-deficient fibroblasts is significantly impaired compared
      with control cells after exposure to relevant doses of UV light. Taken together,
      our results suggest that wild-type p53 can protect cells against UV-induced
      apoptosis by facilitating the recovery of transcription. Furthermore, we suggest
      that the capacity of cells to recover transcription after genotoxic damage is an
      important determinant of sensitivity to apoptosis.

PMID- 10935484
TI  - Noninvasive assessment of tumor cell proliferation in animal models.
AB  - Revealing the mechanisms of neoplastic disease and enhancing our ability to
      intervene in these processes requires an increased understanding of cellular and
      molecular changes as they occur in intact living animal models. We have begun to
      address these needs by developing a method of labeling tumor cells through
      constitutive expression of an optical reporter gene, and noninvasively monitoring
      cellular proliferation in vivo using a sensitive photon detection system. A
      stable line of HeLa cells that expressed a modified firefly luciferase gene was
      generated, and proliferation of these cells in irradiated severe combined
      immunodeficiency (SCID) mice was monitored. Tumor cells were introduced into
      animals via subcutaneous, intraperitoneal and intravenous inoculation and whole
      body images, that revealed tumor location and growth kinetics, were obtained. The
      number of photons that were emitted from the labeled tumor cells and transmitted
      through murine tissues was sufficient to detect 1x10(3) cells in the peritoneal
      cavity, 1x10(4) cells at subcutaneous sites and 1x10(6) circulating cells
      immediately following injection. The kinetics of cell proliferation, as measured
      by photon emission, was exponential in the peritoneal cavity and at subcutaneous
      sites. Intravenous inoculation resulted in detectable colonies of tumor cells in
      animals receiving more than 1x10(6) cells. Our demonstrated ability to detect
      small numbers of tumor cells in living animals noninvasively suggests that
      therapies designed to treat minimal disease states, as occur early in the disease
      course and after elimination of the tumor mass, may be monitored using this
      approach. Moreover, it may be possible to monitor micrometastases and evaluate
      the molecular steps in the metastatic process. Spatiotemporal analyses of
      neoplasia will improve the predictability of animal models of human disease as
      study groups can be followed over time, and this method will accelerate
      development of novel therapeutic strategies.

PMID- 10935485
TI  - Somatic mutations of the PPP2R1B candidate tumor suppressor gene at chromosome
      11q23 are infrequent in ovarian carcinomas.
AB  - Previous studies have demonstrated frequent allelic losses of distal chromosome
      11q in ovarian carcinomas. The tumor suppressor gene(s) presumably targeted by
      these losses have not yet been identified. PPP2R1B is a candidate tumor
      suppressor gene at 11q23 that has recently been shown to be mutated in a subset
      of colorectal and lung cancers. We evaluated 5 ovarian carcinoma cell lines and
      27 primary ovarian carcinomas for allelic losses of 11q23 and for mutations in
      the open reading frame of PPP2R1B. We also evaluated the primary tumors for
      allelic losses at 17p13, another chromosomal region frequently affected by losses
      of heterozygosity (LOH) in ovarian cancers. 11q23 and 17p13 allelic losses were
      identified in 25% and 74% of the carcinomas, respectively. No mutations within
      PPP2R1B coding sequences were found. These findings indicate that mutations of
      the PPP2R1B gene are infrequent in ovarian cancer and that deletions affecting
      the distal portion of chromosome 11q in ovarian cancer likely target inactivation
      of other genes.

PMID- 10935483
TI  - The role of the vascular phase in solid tumor growth: a historical review.
AB  - Angiogenesis is a biological process by which new capillaries are formed from pre
      existing vessels. It occurs in both physiological conditions such as embryo
      development, cyclically in the female genital system and during wound repair, and
      pathological conditions, such as arthritis, diabetic retinopathy and tumors. In
      solid tumor growth, a specific critical turning point is the transition from the
      avascular to the vascular phase. Having developed an intrinsic vascular network,
      the neoplastic mass is able to grow indefinitely (unlike all the other forms,
      tumor angiogenesis is not limited in time) both in situ and at distant sites
      (metastasis) in so far as an intrinsic vascular network enables its cells to
      enter the vascular bed and colonize other organs. Tumor angiogenesis depends
      mainly on the release by neoplastic cells of growth factors specific for
      endothelial cells and able to stimulate growth of the host's blood vessels. This
      review describes its history as traced by the main contributions to the
      international medical literature and their contents. The specific new paradigm
      discussed here has been gaining general approval and considerable confirmation,
      thanks to its possible applications, as recently highlighted by the introduction
      of anti-angiogenic substances in adjuvant tumor management.

PMID- 10935486
TI  - A general approach to the non-invasive imaging of transgenes using cis-linked
      herpes simplex virus thymidine kinase.
AB  - Non-invasive imaging of gene expression opens new prospects for the study of
      transgenic animals and the implementation of genetically based therapies in
      patients. We have sought to establish a general paradigm to enable whole body non
      invasive imaging of any transgene. We show that the expression and imaging of
      HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a
      second gene) under the transcriptional control of a single promoter within a
      bicistronic unit that includes a type II internal ribosomal entry site. In cells
      bearing a single copy of the vector, the expression of the two genes is
      proportional and constant, both in vitro and in vivo. We demonstrate that non
      invasive imaging of HSV1-tk gene accurately reflects the topology and activity of
      the other cis-linked transgene.

PMID- 10935487
TI  - Inhibition of neovascularization and tumor growth, and facilitation of wound
      repair, by halofuginone, an inhibitor of collagen type I synthesis.
AB  - Halofuginone, an inhibitor of collagen alpha1(I) gene expression was used for the
      treatment of subcutaneously implanted C6 glioma tumors. Halofuginone had no
      effect on the growth of C6 glioma spheroids in vitro, and these spheroids showed
      no collagen alpha1(I) expression and no collagen synthesis. However, a
      significant attenuation of tumor growth was observed in vivo, for spheroids
      implanted in CD-1 nude mice which were treated by oral or intraperitoneal (4
      microg every 48 hours) administration of halofuginone. In these mice, treatment
      was associated with a dose-dependent reduction in collagen alpha1(I) expression
      and dose- and time-dependent inhibition of angiogenesis, as measured by MRI.
      Moreover, halofuginone treatment was associated with improved re
      epithelialization of the chronic wounds that are associated with this
      experimental model. Oral administration of halofuginone was effective also in
      intervention in tumor growth, and here, too, the treatment was associated with
      reduced angiogenic activity and vessel regression. These results demonstrate the
      important role of collagen type I in tumor angiogenesis and tumor growth and
      implicate its role in chronic wounds. Inhibition of the expression of collagen
      type I provides an attractive new target for cancer therapy.

PMID- 10935489
TI  - Disruption of imprinted genes at chromosome region 11p15.5 in paediatric
      rhabdomyosarcoma.
AB  - Rhabdomyosarcomas are characterized by loss of heterozygosity (LOH) at chromosome
      region 11p15.5, a region known to contain several imprinted genes including
      insulin-like growth factor 2 (IGF2), H19, and p57(KIP2). We analyzed 48 primary
      tumour samples and found distinct genetic changes at 11p15.5 in alveolar and
      embryonal histological subtypes. LOH was a feature of embryonal tumours, but at a
      lower frequency than previous studies. Loss of imprinting (LOI) of the IGF2 gene
      was detected in 6 of 13 informative cases, all harbouring PAX3-FKHR or PAX7-FKHR
      fusion genes characteristic of alveolar histology. In contrast, H19 imprinting
      was maintained in 14 of 15 informative cases and the case with H19 LOI had
      maintenance of the IGF2 imprint indicating separate mechanisms controlling
      imprinting of IGF2 and H19. The adult promoter of IGF2, P1, was used in 5 of 14
      tumours and its expression was unrelated to IGF2 imprinting status implying a
      further mechanism of altered IGF2 regulation. The putative tumour suppressor gene
      p57(KIP2) was expressed in 15 of 29 tumours and expression was unrelated to
      allele status. Moreover, in tumours with p57(KIP2) expression, there was no
      evidence for inactivating mutations, suggesting that p57(KIP2) is not a tumour
      suppressor in rhabdomyosarcoma.

PMID- 10935490
TI  - ZNF198-FGFR1 transforms Ba/F3 cells to growth factor independence and results in
      high level tyrosine phosphorylation of STATS 1 and 5.
AB  - The ZNF198- FGFR1 fusion gene arises as a result of the t(8;13)(p11;q12) in the
      8p11 myeloproliferative syndrome. To determine the transforming properties of
      this chimeric protein we transfected ZNF198-FGFR1 into the interleukin (IL)-3
      dependent cell line Ba/F3. Growth factor independent subclones were obtained in
      which ZNF198-FGFR1, STAT1, and STAT5 were constitutively tyrosine phosphorylated,
      as determined by immunoprecipitation and Western blot analysis. To test the
      hypothesis that constitutive activation of ZNF198-FGFR1 tyrosine kinase activity
      is a result of self-association of the fusion protein, we in vitro transcribed
      and translated ZNF198-FGFR1 and a derivative construct, ZNF198- FGFR1deltaC-myc,
      in which the C-terminal FGFR1 epitope was replaced by a c-myc tag. As expected,
      an anti-FGFR1 antibody immunoprecipitated ZNF198-FGFR1 but not ZNF198-FGFRdeltaC
      myc. However when both products were translated together, both were
      coimmunoprecipitated by anti-FGFR1 antisera. Similar results were obtained by
      using an anti-myc antibody and demonstrated a physical interaction between the
      two proteins. Analysis of COS-7 cells transfected with ZNF198-FGFR1 demonstrated
      that the fusion gene, in contrast to normal FGFR1, is located in the cytoplasm.
      We conclude that ZNF198-FGFR1 is a cytoplasmic protein that self-associates and
      has constitutive transformation activity. These data suggest that ZNF198-FGFR1
      plays a primary role in the pathogenesis of the t(8;13) myeloproliferative
      syndrome and is the first report to implicate STAT proteins in FGFR1-mediated
      signaling.

PMID- 10935488
TI  - Expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in
      human transitional bladder cancer and its role in inducing cell death.
AB  - The present study examined the expression and role of the thiazolidinedione (TZD)
      activated transcription factor, peroxisome proliferator-activated receptor gamma
      (PPARgamma), in human bladder cancers. In situ hybridization shows that PPARgamma
      mRNA is highly expressed in all human transitional epithelial cell cancers
      (TCCa's) studied (n=11). PPARgamma was also expressed in five TCCa cell lines as
      determined by RNase protection assays and immunoblot. Retinoid X receptor alpha
      (RXRalpha), a 9-cis-retinoic acid stimulated (9-cis-RA) heterodimeric partner of
      PPARgamma, was also co-expressed in all TCCa tissues and cell lines. Treatment of
      the T24 bladder cancer cells with the TZD PPARgamma agonist troglitazone,
      dramatically inhibited 3H-thymidine incorporation and induced cell death.
      Addition of the RXRalpha ligands, 9-cis-RA or LG100268, sensitized T24 bladder
      cancer cells to the lethal effect of troglitazone and two other PPAR- activators,
      ciglitazone and 15-deoxy-delta(12,14)-PGJ2 (15dPGJ(2)). Troglitazone treatment
      increased expression of two cyclin-dependent kinase inhibitors, p21(WAF1/CIP1)
      and p16(INK4), and reduced cyclin D1 expression, consistent with G1 arrest.
      Troglitazone also induced an endogenous PPARgamma target gene in T24 cells,
      adipocyte-type fatty acid binding protein (A-FABP), the expression of which
      correlates with bladder cancer differentiation. In situ hybridization shows that
      A-FABP expression is localized to normal uroepithelial cells as well as some
      TCCa's. Taken together, these results demonstrate that PPARgamma is expressed in
      human TCCa where it may play a role in regulating TCCa differentiation and
      survival, thereby providing a potential target for therapy of uroepithelial
      cancers.

PMID- 10935491
TI  - The "comparative growth assay": examining the interplay of anti-cancer agents
      with cells carrying single gene alterations.
AB  - We have developed a "comparative growth assay" that complements current assays of
      drug effects based on cytotoxicity. A co-culture of two cell lines, one of which
      is fluorescently labeled, is exposed to a cytotoxic agent and the proportion of
      fluorescent cells is compared with that of a baseline unexposed co-culture. For
      demonstration purposes, two HCT116 cell lines (an hMLH1 homozygous and an hMLH1
      heterozygous mutant), altered by insertion of vector alone or the same vector
      carrying an insert for the expression of enhanced green fluorescent protein
      (EGFP), were exposed to numerous "anti-cancer" agents. The assay was further
      validated in a system of two cell lines differing only in the expression of the
      breast cancer resistance protein (BRCP). The assay allowed the estimation of the
      duration of action of a particular agent. Assessment of the agent's differential
      activity over a given time in culture could be expressed as a selection rate,
      which we chose to describe on an "average selection per day" basis. We conclude
      that this assay: 1) provides insight into the differential dynamic effects of
      chemotherapeutic agents or radiation; and 2) allows, through the use of matched
      cell lines, the investigation of critical physiologic features that govern cell
      sensitivity.

PMID- 10935494
TI  - The Susan G. Komen Breast Cancer Foundation.

PMID- 10935492
TI  - Transcriptional inhibition of matrix metalloproteinase 9 (MMP-9) activity by a c
      fos/estrogen receptor fusion protein is mediated by the proximal AP-1 site of the
      MMP-9 promoter and correlates with reduced tumor cell invasion.
AB  - Tumor cell invasion of basement membranes is one of the hallmarks of malignant
      transformation. Tumor cells secrete proteolytic enzymes known as matrix
      metalloproteinases (MMPs) which degrade extracellular matrix molecules. Increased
      expression of MMP-9 has been associated with acquisition of invasive phenotype in
      many tumors. However, multiple mechanisms for regulation of MMP-9 gene expression
      by tumor cell lines have been proposed. A number of transcription factor binding
      sites have been characterized in the upstream regulatory region of the MMP-9
      gene, including those for AP-1. To determine how a specific AP-1 family member, c
      fos, regulates MMP-9 promoter activity through these sites, we used an expression
      vector containing the c-fos coding region fused to the estrogen receptor (ER)
      ligand binding domain. This construct is activated upon binding estradiol. Stable
      expression of this construct in ER negative squamous cell carcinoma (SCC) lines
      produced an estradiol dependent decrease in the number of cells that migrated
      through a reconstituted basement membrane. This decreased invasiveness was
      accompanied by estradiol dependent downregulation of MMP-9 activity as determined
      by gelatin zymography. Estradiol also produced transcriptional downregulation of
      an MMP-9 promoter construct in cells transiently transfected with the c-fosER
      expression vector. This downregulation was mediated by the AP-1 site at -79 bp in
      the MMP-9 promoter. We concluded that the proximal AP-1 site mediated the
      transcriptional downregulation of the MMP-9 promoter by a conditionally activated
      c-fos fusion protein.

PMID- 10935493
TI  - Protein kinase A regulatory subunits in colon cancer.
AB  - The protein kinase A (PKA) is classified as type I or II depending on the
      association of the catalytic subunit with either the R(I) or R(II) regulatory
      subunits. Alterations in the levels of these regulatory subunits and PKA activity
      itself appear to affect cellular proliferation and tumorigenesis. We examined
      colorectal tumor specimens from 45 patients to investigate the potential role of
      cAMP-related signaling molecules in regulating tumorigenesis. Western blot
      analysis (PKA subunit protein levels) and in vitro kemptide phosphorylation
      assays (PKA catalytic subunit activity) were performed on human colorectal tumor
      tissue homogenates. R(I)beta protein levels were decreased 200% in ascending and
      50% in descending colonic tumors compared to adjacent mucosa. R(II) protein
      levels were decreased 77% in descending colonic tumors but no change was observed
      in ascending colonic tumors compared to adjacent mucosa. PKA activity and the
      absolute amount of catalytic subunit protein in ascending and descending tumors
      were unchanged compared to adjacent mucosa. Differences in cAMP-related signaling
      molecules exist between neoplastic and normal colorectal tissues. These
      differences may not only serve as potential therapeutic targets for
      chemotherapeutic agents, but also lead to the identification of novel regulatory
      mechanisms involved in cellular proliferation and tumorigenesis.

PMID- 10935496
TI  - Molecular cytogenetics investigation of the telomeres in a case of Philadelphia
      positive B-ALL with a single telomere expansion.
AB  - We have investigated a single telomere expansion in a case of acute lymphoblastic
      B-cell leukemia (B-ALL), where half of the cells in the bone marrow sample
      appeared with a Philadelphia chromosome. Comparing telomere sizes in Philadelphia
      positive versus -negative cells, we found generally shorter telomeres in the
      Philadelphia-positive cells, but with an expansion of the telomere on the long
      arm of one chromosome 11 homologue. This expansion was also found in a minority
      of Philadelphia-negative cells. The telomeres in these cells were of the same
      overall size as the telomeres in the Philadelphia-negative cells without the 11q
      expansion. Together, these findings suggest that the order of events was: 11q
      telomere expansion, Philadelphia translocation, overall telomere shortening. The
      expanded 11q telomere contained the standard telomeric (AGGGTT)(n) repeat, but
      also variant repeat sequences. The single telomere expansion suggests a non
      telomerase mechanism behind the expansion which may also explain the presence of
      variant repeats in the expanded telomere. The present case illustrates that
      telomere changes may occur at only some chromosome ends in a subset of cells. To
      reveal such changes, telomere morphology should be studied with in situ
      methodology.

PMID- 10935495
TI  - Calcium-induced activation of a mutant G-protein-coupled receptor causes in vitro
      transformation of NIH/3T3 cells.
AB  - The calcium-sensing receptor (CaR) is a G-protein-coupled receptor that is widely
      expressed, has tissue-specific functions, and regulates cell growth. Activating
      mutations of this receptor cause autosomal dominant hypocalcemia, a syndrome
      characterized by hypocalcemia and hypercalciuria. The identification of a family
      with an activating mutation of the CaR (Thr151Met) in which hypocalcemia
      cosegregates with several unusual neoplasms led us to examine the transforming
      effects of this mutant receptor. Transfection of NIH/3T3 cells with the mutant
      but not the normal receptor supported colony formation in soft agar at
      subphysiologic calcium concentrations. The mutant CaR causes a calcium-dependent
      activation of the extracellular signal-regulated protein kinase (ERK) 1/2 and Jun
      N-terminal kinase/stress-activated (JNK/ SAPK) pathways, but not P38 MAP kinase.
      These findings contribute to a growing body of information suggesting that this
      receptor plays a role in the regulation of cellular proliferation, and that
      aberrant activation of the mutant receptor in this family may play a role in the
      unusual neoplastic manifestations.

PMID- 10935497
TI  - Novel suicide ligands of tubulin arrest cancer cells in S-phase.
AB  - It is presently accepted that the mechanism of action for all anti-tumor tubulin
      ligands involves the perturbation of microtubule dynamics during the G2/M phase
      of cell division and subsequent entry into apoptosis [1]. In this report, we
      challenge the established dogma by describing a unique mechanism of action caused
      by a novel series of tubulin ligands, halogenated derivatives of acetamido
      benzoyl ethyl ester. We have developed a suicide ligand for tubulin, which
      covalently attaches to the target and shows potent cancericidal activity in
      tissue culture assays and in animal tumor models. These compounds target early S
      phase at the G1/S transition rather than the G2/M phase and mitotic arrest. Bcl-2
      phosphorylation, a marker of mitotic microtubule inhibition by other tubulin
      ligands was dramatically altered, phosphorylation was rapid and biphasic rather
      than a slow linear event. The halogenated ethyl ester series of derivatives thus
      constitute a unique set of tubulin ligands which induce a novel mechanism of
      apoptosis.

PMID- 10935499
TI  - Changes in vascularization of human breast cancer xenografts responding to
      antiestrogen therapy.
AB  - To elucidate the previously suggested vascular effect(s) of antiestrogen therapy,
      we studied the effect of estrogen withdrawal and tamoxifen on 1) vascular
      resistance, 2) glucose and oxygen consumption, and 3) vascular density in a
      perfused breast cancer line (ZR75-1). Furthermore, we examined ZR75-1 tumors by
      functional CT-scanning (fCT) to determine changes in parameters related to tumor
      capillary transfer constants and vascular volume fraction in response to
      antiestrogenic manipulations. The vascular resistance decreased significantly
      from 42.7 to 20.8 mmHg x min x g x ml(-1) (P< .03) on day 9 after estrogen
      withdrawal, but not after 9 days of tamoxifen treatment. The estrogen-depleted
      tumors were significantly smaller than controls on day 9. There was no difference
      in nutrient consumption or vascular density in any of the experimental groups
      compared to controls. fCT showed an increase (P < .03) in vascular volume
      fraction during tumor growth, and this parameter was significantly lower after
      estrogen withdrawal when compared to controls (P < .05). Vascular resistance
      correlated with tumor size (R = 0.7, P < .0001), indicating that vascular
      resistance increases during tumor growth. The changes in vascular parameters
      after estrogen withdrawal indicate a vascular remodeling effect. This inhibition
      of vascular development by hormone deprivation may have important implications
      for future planning of multimodal treatment regimens.

PMID- 10935500
TI  - Tel, a frequent target of leukemic translocations, induces cellular aggregation
      and influences expression of extracellular matrix components.
AB  - Tel is an Ets transcription factor that is the target of chromosome
      translocations in lymphoid and myeloid leukemias and in solid tumors. It contains
      two functional domains, a pointed oligomerization domain and a DNA-binding
      domain. Retroviral transduction of a wild-type Tel cDNA into a clonal subline of
      NIH3T3 fibroblasts resulted in a striking morphologic change: at confluency, the
      cells reorganized into a specific "bridge-like" pattern over the entire surface
      of the culture dish, and started migrating, thereby leaving circular holes in the
      monolayer. Thereafter, formation of cellular cords became apparent. This sequence
      of events was inhibited by coating the culture dishes with fibronectin and
      collagen IV. Retroviral transduction of Tel into MS1 endothelial cells reproduced
      the aggregation phenotype, but not the cellular cord formation. Tel-mutagenesis
      showed that both the pointed domain and the DNA-binding domain of Tel are
      required for the morphologic change. Other Ets family genes, Fli-1 and Ets-1 that
      are both endogenously expressed in endothelial cells, could not induce this
      morphologic change. Exogenous Tel expression is associated with transcriptional
      upregulation of entactin/nidogen, Smad5, Col3a1, CD44 and fibronectin, and
      downregulation of Col1a1 and secretory leukocyte protease inhibitor.
      Interestingly, Tel, Smad5, fibronectin, Col1a1 and Col3a1 all have essential
      roles during vascular development.

PMID- 10935498
TI  - Synergistic induction of cyclooxygenase-2 by transforming growth factor-beta1 and
      epidermal growth factor inhibits apoptosis in epithelial cells.
AB  - Increased expression of cyclooxygenase-2 (COX-2) expression has been observed in
      several human tumor types and in selected animal and cell culture models of
      carcinogenesis, including lung cancer. Increased expression of COX-2 and
      production of prostaglandins appear to provide a survival advantage to
      transformed cells through the inhibition of apoptosis, increased attachment to
      extracellular matrix, increased invasiveness, and the stimulation of
      angiogenesis. In the present studies, we found that transforming growth factor
      beta1 (TGF-beta1) and epidermal growth factor (EGF) synergistically induced the
      expression of COX-2 and prostaglandin E2 (PGE2) production in mink lung
      epithelial (Mv1Lu) cells. EGF, but not PDGF or IGF-1, was able to inhibit TGF
      beta1-induced apoptosis in Mv1Lu cells and this effect was blocked by NS-398, a
      selective inhibitor of COX-2 activity, suggesting a possible role for COX-2 in
      the anti-apoptotic effect of EGF receptor ligands. The combination of TGF-beta1
      and EGF also significantly induced COX-2 expression in rat intestinal epithelial
      (RIE-1) cells and completely prevented sodium butyrate (NaBu)-induced apoptosis.
      The synergistic induction of COX-2 by TGF-beta1 and EGF was not observed in R1B
      L17 cells, a line derived from Mv1Lu cells that lacks the TGF-beta type-I
      receptor. AG1478, a selective inhibitor of EGF receptor tyrosine kinase activity,
      completely suppressed the induction of COX-2 expression by either EGF or TGF
      beta1+EGF. Also, PD98059, a specific inhibitor of MEK/ERK pathway, and SB203580,
      a specific inhibitor of p38 MAPK activity, significantly inhibited the induction
      of COX-2 in response to combined EGF and TGF-beta1. These results suggest an
      important collaborative interaction of TGF-beta1 and EGF signaling in the
      induction of COX-2 and prostaglandin production in Mv1Lu cells.

PMID- 10935501
TI  - Response of hepatoma 9618a and normal liver to host carbogen and carbon monoxide
      breathing.
AB  - The effects of hyperoxia (induced by host carbogen [95% oxygen/5% carbon dioxide
      breathing] and hypoxia (induced by host carbon monoxide [CO at 660 ppm]
      breathing) were compared by using noninvasive magnetic resonance (MR) methods to
      gain simultaneous information on blood flow/oxygenation and the bioenergetic
      status of rat Morris H9618a hepatomas. Both carbogen and CO breathing induced a
      1.5- to 2-fold increase in signal intensity in blood oxygenation level dependent
      (BOLD) MR images. This was due to a decrease in deoxyhemoglobin (deoxyHb), which
      acts as an endogenous contrast agent, caused either by formation of oxyhemoglobin
      in the case of carbogen breathing, or carboxyhemoglobin with CO breathing. The
      results were confirmed by observation of similar changes in deoxyHb in arterial
      blood samples examined ex vivo after carbogen or CO breathing. There was no
      change in nucleoside triphosphates (NTP)/P(i) in either tumor or liver after CO
      breathing, whereas NTP/P(i) increased twofold in the hepatoma (but not in the
      liver) after carbogen breathing. No changes in tumor intracellular pH were seen
      after either treatment, whereas extracellular pH became more alkaline after CO
      breathing and more acid after carbogen breathing, respectively. This tumor type
      and the liver are unaffected by CO breathing at 660 ppm, which implies an
      adequate oxygen supply.

PMID- 10935503
TI  - Tumoral environment triggers transcript anomalies in established tumors:
      induction of altered gene expression and of aberrant, truncated and B2 repeat
      containing gene transcripts.
AB  - In addition to eugenetic changes, cancerous cells exhibit extensive modifications
      in the expression levels of a variety of genes. The phenotypic switch observed
      after inoculation of T lymphoma cells into syngenic mice illustrates the active
      participation of tumoral environment in the induction of an aberrant gene
      expression pattern. To further substantiate this contribution, we performed
      polymerase chain reaction (PCR)-based subtraction suppression hybridization (SSH)
      to identify genes that are differentially expressed in tumor-derived EL4/13.3
      cells compared to the same cells isolated from cultures. Besides a number of
      unknown genes, the subtracted library contained several known genes that have
      been reported to be expressed at increased levels in tumors and/or to contribute
      to carcinogenesis. Apart from clones representing translated transcripts, the
      subtracted library also contained a high number of clones representing B2 repeat
      elements, viz. short interspersed repetitive elements that are transcribed by RNA
      polymerase III. Northern blotting confirmed the induction of B2 transcripts in
      tumor tissue and also revealed induction of chimeric, B2 repeat-containing mRNA.
      The appearance of chimeric transcripts was accompanied by aberrant, shorter-than
      full-length transcripts, specifically from upregulated genes. Accordingly, in
      addition to altered gene expression, tumoral environmental triggers constitute a
      potent mechanism to create an epigenetic diversity in cancers by inducing
      extensive transcript anomalies.

PMID- 10935502
TI  - p53-independent inhibition of proliferation and p21(WAF1/Cip1)-modulated
      induction of cell death by the antioxidants N-acetylcysteine and vitamin E.
AB  - Epidemiological evidence has suggested an association between diets rich in
      antioxidants and diminished risks of various types of cancer. Proposed mechanisms
      for protective effects of antioxidants have involved inhibition of free radical
      mediated DNA damage. Recent data suggest that antioxidants may prevent or
      eliminate cancerous cells through their ability to inhibit proliferation or to
      induce programmed cell death (PCD). To begin to identify cell cycle and cell
      death regulatory factors involved in antioxidant-induced growth arrest and PCD,
      we have studied colorectal carcinoma cells (CRCs) that differ in expression of
      the tumor suppressor protein p53, and of the cyclin-dependent kinase (CDK)
      inhibitor p21(Waf1/Cip1). The antioxidants, N-acetylcysteine (NAC) and vitamin E
      either inhibited proliferation in a p53-independent manner without affecting cell
      viability or induced cell death. Growth arrest was not associated with
      upregulation of the CDK inhibitors p21(Waf1/Cip1), p18(ink4c) or p16(ink4a), but
      was associated with a decrease in reactive oxygen species (ROS). In contrast to
      previous observations, the absence of p21(Waf1/Cip1) increased susceptibility of
      CRCs to antioxidant-induced PCD. NAC decreased levels of retinoblastoma protein
      (Rb) phosphorylation in all cells tested, but Rb was cleaved only in cells which
      underwent NAC-induced death. Although NAC decreased ROS in all cells studied,
      cell lines in which PCD occurred had higher baseline levels of ROS than cell
      lines in which proliferation was blocked. These observations suggest that
      expression of p21(Waf1/Cip1) and basal levels of ROS are important determinants
      of outcome after antioxidant treatment.

PMID- 10935504
TI  - Implications of mapping the human telomerase gene (hTERT) as the most distal gene
      on chromosome 5p.

PMID- 10935505
TI  - Mapping of the gene for the human telomerase reverse transcriptase, hTERT, to
      chromosome 5p15.33 by fluorescence in situ hybridization.
AB  - Telomerase, the enzyme that maintains the ends of chromosomes, is absent from the
      majority of somatic cells but is present and active in most tumours. The gene for
      the reverse transcriptase component of telomerase (hTERT) has recently been
      identified. A cDNA clone of this gene was used as a probe to identify three
      genomic bacterial artificial chromosome (BAC) clones, one of which was used as a
      probe to map hTERT by fluorescence in situ hybridization (FISH) to chromosome
      5p15.33. This BAC probe was further used to look at copy number of the hTERT
      region in immortal cell lines. We found that 10/15 immortal cell lines had a
      modal copy number of 3 or more per cell, with one cell line (CaSki) having a
      modal copy number of 11. This suggests that increases in copy number of the hTERT
      gene region do occur, and may well be one route to upregulating telomerase levels
      in tumour cells. 5p15 gains and amplifications have been documented for various
      tumour types, including non-small cell lung carcinoma, squamous cell carcinoma of
      head and neck, and uterine cervix cancer, making hTERT a potential target.

PMID- 10935506
TI  - Driving p53 response to Bax activation greatly enhances sensitivity to taxol by
      inducing massive apoptosis.
AB  - The proapoptotic gene bax is one of the downstream effectors of p53. The p53
      binding site in the bax promoter is less responsive to p53 than the one in the
      growth arrest mediating gene p21. We introduced the bax gene under the control of
      13 copies of a strong p53 responsive element into two ovarian cancer cell lines.
      The clones expressing bax under the control of p53 obtained from the wild-type
      (wt) p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold)
      to the anticancer agent taxol than the parent cell line, with a higher percentage
      of cells undergoing apoptosis after drug treatment that was clearly p53-dependent
      and bax-mediated. Xenografts established in nude mice from one selected clone
      (A2780/C3) were more responsive to taxol than the parental line and the apoptotic
      response of A2780/C3 tumors was also increased after treatment. Introduction of
      the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity
      to taxol or the induction of apoptosis. In conclusion, driving the p53 response
      (after taxol treatment) by activating the bax gene rather than the p21 gene
      results in induction of massive apoptosis, in vitro and in vivo, and greatly
      enhances sensitivity to the drug.

PMID- 10935508
TI  - Activation of hepatocyte growth factor-met autocrine loop enhances tumorigenicity
      in a human lung adenocarcinoma cell line.
AB  - Hepatocyte growth factor (HGF) is a multifunctional cytokine with effects on the
      proliferation, motility, and differentiation of cells that express its receptor
      Met. The co-expression of HGF and Met is common among nonsmall-cell lung cancers,
      especially adenocarcinoma. However, the biologic consequences of this putative
      HGF-Met autocrine signaling remain speculative. We have used retroviral gene
      transduction technique to express high levels of HGF in the NCI-H358 lung
      adenocarcinoma cells that have functionally active cell surface Met receptor. The
      activation of autocrine HGF-Met signaling was confirmed by the induction of
      spontaneous cell scattering activity. Compared to the parent and control cells
      transduced with the retroviral vector alone, HGF overexpressing H358 cells show
      enhanced capacity to colonize soft agar medium and to form xenograft tumors when
      implanted in the subcutaneous tissue of immune-deficient mice. These effects were
      not accompanied by changes in their growth rate in monolayer culture condition,
      or in the expression of vascular endothelial growth factor. The tumors formed by
      HGF overexpressing cells also showed more prominent glandular cell arrangement
      and functional activity. This report provides the direct in vivo evidence that
      autocrine HGF-Met signaling plays significant roles in the growth and
      differentiation of human lung adenocarcinoma cells.

PMID- 10935509
TI  - Down-regulation of survivin by antisense oligonucleotides increases apoptosis,
      inhibits cytokinesis and anchorage-independent growth.
AB  - Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is
      detected in most common human cancers but not in adjacent normal cells. Previous
      studies suggest that survivin associates with the mitotic spindle and directly
      inhibits caspase activity. To further investigate the function of survivin, we
      used a survivin antisense (AS) oligonucleotide to downregulate survivin
      expression in normal and cancer cells. We found that inhibition of survivin
      expression increased apoptosis and polyploidy while decreasing colony formation
      in soft agar. Immunohistochemistry showed that cells without survivin can
      initiate the cleavage furrow and contractile ring, but cannot complete
      cytokinesis, thus resulting in multinucleated cells. These findings indicate that
      survivin plays important roles in a late stage of cytokinesis, as well as in
      apoptosis.

PMID- 10935510
TI  - Antagonists of growth hormone-releasing hormone inhibit the growth of U-87MG
      human glioblastoma in nude mice.
AB  - Antagonists of growth hormone-releasing hormone(GH-RH)inhibit the growth of
      various cancers by mechanisms that involve the suppression of the insulin-like
      growth factor (IGF)-I and/or IGF-II. In view of the importance of the IGF system
      in glioma tumorigenesis, the effects of GH-RH antagonists MZ-5-156 and JV-1-36
      were investigated in nude mice bearing subcutaneous and orthotopic xenografts of
      U-87MG human glioblastomas. After 4 weeks of therapy with MZ-5-156 or JV-1 -36 at
      the dose of 20 microg/day per animal, the final volume of subcutaneous U-87MG
      tumors was significantly (P < .01) decreased by 84% and 76%, respectively, as
      compared with controls. Treatment with GH-RH antagonists also reduced tumor
      weight and the levels of mRNA for IGF receptor type I (IGFR-I). A reduction in
      the mRNA levels for IGF-II was found in tumors of mice treated with MZ-5-156.
      Treatment with MZ-5-156 or JV-1 -36 also extended the survival of nude mice
      implanted orthotopically with U-87MG glioblastomas by 81% (P < .005) and 18%,
      respectively, as compared with the controls. Exposure in vitro to GH-RH
      antagonists MZ-5-156 or JV-1 -36 at 1 microM concentration for 24 hours decreased
      the tumorigenicity of U-87MG cells in nude mice by 10% to 30% and extended the
      latency period for the development of subcutaneous palpable tumors by 31% to 56%,
      as compared with the controls. Exposure of U-87MG cells to GH-RH antagonists in
      vitro also resulted in a time-dependent increase in the mRNA levels of IGFR-II or
      a decrease in the mRNA levels of IGFR-I. mRNA for GH-RH was detected in U-87MG
      cells and xenografts implying that GH-RH may play a role in the pathogenesis of
      this tumor. Our results suggest that GH-RH antagonists MZ-5-156 and JV-1-36
      inhibit the growth of U-87MG human glioblastoma by mechanisms that involve the
      suppression of IGF system. Antagonistic analogs of GH-RH merit further
      development for the treatment of malignant glioblastoma.

PMID- 10935511
TI  - A bcl-xS adenovirus selectively induces apoptosis in transformed cells compared
      to normal mammary cells.
AB  - Oncogenes which drive the cell cycle, such as c-myc, can sensitize cells to
      apoptosis. This suggests the possibility that the expression of genes such as bcl
      2 or bcl-xL is required to inhibit apoptosis induced by oncogene expression. We
      hypothesized that inhibition of Bcl-2/Bcl-xL by the pro-apoptotic Bcl-xS protein,
      would result in selective induction of apoptosis in mammary carcinoma cells
      compared to their nontransformed counterparts. Therefore, we compared the effects
      of Bcl-xS expression delivered by a bcl-xS adenovirus (bcl-xS-Adv) vector, on
      viability and apoptosis of nontransformed versus transformed mammary epithelial
      cells. We report that c-myc-transformed murine mammary cells are extremely
      sensitive to apoptosis induced by the bcl-xS adenovirus (bcl-xS-Adv) vector,
      whereas immortalized, nontransformed murine mammary cells are relatively
      resistant to apoptosis induced by this vector. Likewise, human mammary epithelial
      cells transduced with c-erbB-2 were more sensitive to apoptosis induced by the
      bcl-xS vector than the nontransformed parental cells. Similar results were
      obtained when we tested the effects of bcl-xS adenoviral infection on primary
      normal human mammary epithelial cells and SUM-190 PT cells, (a c-erbB-2 over
      expressing human mammary carcinoma cell line) grown on Matrigel. These data are
      consistent with the hypothesis that inhibition of Bcl-2/Bcl-xL can result in
      selective killing of cancer cells compared to their nontransformed counterparts.

PMID- 10935513
TI  - Imaging prostate cancer invasion with multi-nuclear magnetic resonance methods:
      the Metabolic Boyden Chamber.
AB  - The physiological milieu within solid tumors can influence invasion and
      metastasis. To determine the impact of the physiological environment and cellular
      metabolism on cancer cell invasion, it is necessary to measure invasion during
      well-controlled modulation of the physiological environment. Recently, we
      demonstrated that magnetic resonance imaging can be used to monitor cancer cell
      invasion into a Matrigel layer [Artemov D, Pilatus U, Chou S, Mori N, Nelson JB,
      and Bhujwalla ZM (1999). Dynamics of prostate cancer cell invasion studied in
      vitro by NMR microscopy. Mag Res Med 42, 277-282.]. Here we have developed an
      invasion assay ("Metabolic Boyden Chamber") that combines this capability with
      the properties of our isolated cell perfusion system. Long-term experiments can
      be performed to determine invasion as well as cellular metabolism under
      controlled environmental conditions. To characterize the assay, we performed
      experiments with prostate cancer cell lines preselected for different invasive
      characteristics. The results showed invasion into, and degradation of the
      Matrigel layer, by the highly invasive/metastatic line (MatLyLu), whereas no
      significant changes were observed for the less invasive/metastatic cell line (DU
      145). With this assay, invasion and metabolism was measured dynamically, together
      with oxygen tensions within the cellular environment and within the Matrigel
      layer. Such a system can be used to identify physiological and metabolic
      characteristics that promote invasion, and evaluate therapeutic interventions to
      inhibit invasion.

PMID- 10935512
TI  - K-Ras-independent effects of the farnesyl transferase inhibitor L-744,832 on
      cyclin B1/Cdc2 kinase activity, G2/M cell cycle progression and apoptosis in
      human pancreatic ductal adenocarcinoma cells.
AB  - Pancreatic ductal adenocarcinoma is a highly lethal malignancy that is resistant
      to traditional cytotoxic therapy. High rates of activating codon 12 K-Ras
      mutations in this disease have generated considerable interest in the therapeutic
      application of novel farnesyl transferase inhibitors (FTIs). However, a
      comprehensive analysis of the effects of FTI treatment on pancreatic cancer cells
      has not been performed. Treatment of five different human pancreatic cancer cell
      lines with FTI L-744,832 resulted in inhibition of anchorage-dependent growth,
      with wide variation in sensitivity among different lines. Effective growth
      inhibition by L-744,832 correlated with accumulation of cells with a tetraploid
      (4N) DNA content and high levels of cyclin B1/cdc2 kinase activity, implying cell
      cycle arrest downstream from the DNA damage-inducible G2/M cell cycle checkpoint.
      In addition, sensitive cell lines underwent apoptosis as evidenced by changes in
      nuclear morphology and internucleosomal DNA fragmentation. L-744,832 at a
      concentration of 1 microM additively enhanced the cytotoxic effect of ionizing
      radiation, apparently by overriding G2/M checkpoint activation. The effects of
      FTI treatment on cell growth and cell cycle regulation were associated with
      changes in posttranslational processing of H-Ras and N-Ras, but not K-Ras. The
      results confirm the potential therapeutic efficacy of FTI treatment in pancreatic
      cancer, and suggest that farnesylated proteins other than K-Ras may act as
      important regulators of G2/M cell cycle kinetics.

PMID- 10935507
TI  - Dial 9-1-1 for p53: mechanisms of p53 activation by cellular stress.
AB  - The tumor suppressor protein, p53, is part of the cell's emergency team that is
      called upon following cellular insult. How do cells sense DNA damage and other
      cellular stresses and what signal transduction pathways are used to alert p53?
      How is the resulting nuclear accumulation of p53 accomplished and what determines
      the outcome of p53 induction? Many posttranslational modifications of p53, such
      as phosphorylation, dephosphorylation, acetylation and ribosylation, have been
      shown to occur following cellular stress. Some of these modifications may
      activate the p53 protein, interfere with MDM2 binding and/or dictate cellular
      localization of p53. This review will focus on recent findings about how the p53
      response may be activated following cellular stress.

PMID- 10935515
TI  - Lymphoma Research Foundation of America: shedding light and saving lives.

PMID- 10935514
TI  - Classical oncogenes and tumor suppressor genes: a comparative genomics
      perspective.
AB  - We have curated a reference set of cancer- related genes and reanalyzed their
      sequences in the light of molecular information and resources that have become
      available since they were first cloned. Homology studies were carried out for
      human oncogenes and tumor suppressors, compared with the complete proteome of the
      nematode, Caenorhabditis elegans, and partial proteomes of mouse and rat and the
      fruit fly, Drosophila melanogaster. Our results demonstrate that simple, semi
      automated bioinformatics approaches to identifying putative functionally
      equivalent gene products in different organisms may often be misleading. An
      electronic supplement to this article provides an integrated view of our
      comparative genomics analysis as well as mapping data, physical cDNA resources
      and links to published literature and reviews, thus creating a "window" into the
      genomes of humans and other organisms for cancer biology.

PMID- 10935516
TI  - The protective effects of hypoxia-induced hypometabolism in the Nautilus.
AB  - Specimens of Nautilus pompilius were trapped at depths of 225-300 m off the
      sunken barrier reef southeast of Port Moresby, Papua New Guinea. Animals
      transported to the Motupore Island laboratory were acclimated to normal habitat
      temperatures of 18 degrees C and then cannulated for arterial and venous blood
      sampling. When animals were forced to undergo a period of progressive hypoxia
      eventually to encounter ambient partial pressure of oxygen (PO2) levels of
      approximately 10 mmHg (and corresponding arterial PO2's of approximately 5 mmHg),
      they responded by lowering their aerobic metabolic rates to 5-10% of those seen
      in resting normoxic animals. Coincident with this profound metabolic suppression
      was an overall decrease in activity, with brief periods of jet propulsion
      punctuating long periods of rest. Below ambient PO2 levels of 30-40 mmHg,
      ventilatory movements became highly periodic and at the lowest PO2 levels
      encountered, ventilation occasionally ceased altogether. Cardiac output estimated
      by the Fick equation decreased during progressive hypoxia by as much as 75 80%,
      and in the deepest hypometabolic states heart rates slowed to one to two cycles
      of very low amplitude per minute. By the end of 500 min exposure to ambient PO2
      levels of 10 mmHg or less, the anaerobic end products octopine and succinate had
      increased significantly in adductor muscle and heart, respectively. Increased
      concentrations of octopine in adductor muscle apparently contributed to a small
      intracellular acidosis and to the development of a combined respiratory and
      metabolic acidosis in the extracellular compartment. On the other hand, increases
      in succinate in heart muscle occurred in the absence of any change in cardiac
      pHi. Taken together, we estimate that these anaerobic end products would make up
      less than 2% of the energy deficit arising from the decrease in aerobic
      metabolism. Thus, metabolic suppression is combined with a massive downregulation
      of systemic O2 delivery to match metabolic supply to demand.

PMID- 10935517
TI  - How incubation temperature influences the physiology and growth of embryonic
      lizards.
AB  - Eggs of two small Australian lizards, Lampropholis guichenoti and Bassiana
      duperreyi, were incubated to hatching at 25 degrees C and 30 degrees C.
      Incubation periods were significantly longer at 25 degrees C in both species, and
      temperature had a greater effect on the incubation period of B. duperreyi (41.0
      days at 25 degrees C; 23.1 days at 30 degrees C) than L. guichenoti (40.1 days at
      25 degrees C; 27.7 days at 30 degrees C). Patterns of oxygen consumption were
      similar in both species at both temperatures, being sigmoidal in shape with a
      fall in the rate of oxygen consumption just prior to hatching. The higher
      incubation temperature resulted in higher peak and higher prehatch rates of
      oxygen consumption in both species. Total amount of oxygen consumed during
      incubation was independent of temperature in B. duperreyi, in which approximately
      50 ml oxygen was consumed at both temperatures, but eggs of L. guichenoti
      incubated at 30 degrees C consumed significantly more (32.6 ml) than eggs
      incubated at 25 degrees C (28.5 ml). Hatchling mass was unaffected by either
      incubation temperature or the amount of water absorbed by eggs during incubation
      in both species. The energetic production cost of hatchling B. duperreyi (3.52 kJ
      x g(-1)) was independent of incubation temperature, whereas in L. guichenoti the
      production cost was greater at 30 degrees C (4.00 kJ x g(-1)) than at 25 degrees
      C (3.47 kJ g(-1)). Snout-vent lengths and mass of hatchlings were unaffected by
      incubation temperature in both species, but hatchling B. duperreyi incubated at
      30 degrees C had longer tails (29.3 mm) than those from eggs incubated at 25
      degrees C (26.2 mm). These results indicate that incubation temperature can
      affect the quality of hatchling lizards in terms of embryonic energy consumption
      and hatchling morphology.

PMID- 10935518
TI  - Transfer of fatty acids from female seal blubber via milk to pup bladder.
AB  - Fatty acids were determined by gas chromatography followed by principal component
      analysis (PCA) and soft independent modelling of class analogy (SIMCA) in the
      blubber of 18 female grey seals, Halichoerus grypus, in their milk and in the
      blubber of their 1-week-old nursing pups. Large individual differences were
      observed in both blubber and milk content of fatty acids. The fatty acid
      composition of the milk was systematically different from the composition in
      maternal blubber, with higher relative amounts of the saturated acids, the
      monounsaturated with 20 carbon atoms and the n3 polyunsaturated, except 18:3n3.
      The composition of the fatty acids in the blubber of the pups was different from
      that of the milk. The same fatty acids that were enriched in the milk were
      depleted in the blubber of the pups. Therefore the fatty acid composition in the
      blubber of the pups was similar to that in the adults, although not identical.
      The results from this investigation imply that the composition of the fatty acids
      in the blubber of female seals and in the blubber of their pups cannot be
      determined directly by analysis of fatty acid composition of milk.

PMID- 10935519
TI  - Seasonal change and prolonged anoxia affect the kinetic properties of
      phosphofructokinase and pyruvate kinase in oysters.
AB  - The effects of seasonal change, November versus July, and prolonged anoxia (96 h
      under N2 gas) on the properties of phosphofructokinase and pyruvate kinase from
      five tissues (gill, mantle, hepatopancreas, phasic adductor, catch adductor) of
      the oyster, Crassostrea virginica were investigated. Both enzymes showed tissue
      specific and season-specific changes in kinetic properties; for pyruvate kinase
      this correlated with seasonal differences in enzyme elution patterns on
      hydroxylapatite chromatography. Kinetic properties of both enzymes in winter were
      consistent with primarily catabolic roles in glycolysis with responsiveness to
      cellular energy demands, whereas in summer these enzymes may be more closely
      regulated with respect to the biosynthetic and gluconeogenic functions of the
      tissues. Anoxia-induced changes in phosphofructokinase properties were relatively
      minor but anoxia stimulated changes in pyruvate kinase properties and elution
      profiles on hydroxylapatite in all tissues except mantle, with much greater
      effects seen for the enzyme from winter versus summer animals. For example,
      anoxia-induced changes in pyruvate kinase from winter gill included a fourfold
      rise in the substrate affinity constant for phosphoenolpyruvate, a sevenfold
      increase in the concentration of fructose-1,6-bisphosphate needed to activate the
      enzyme by 50%, and a 50% decrease in the concentration of L-alanine that inhibits
      activity by 50%. Changes in pyruvate kinase kinetics and hydroxylapatite elution
      patterns during prolonged anoxia are consistent with covalent modification of
      pyruvate kinase but contrary to results for many other mollusc species, anoxia
      exposure appears to induce a dephosphorylation of the enzyme.

PMID- 10935522
TI  - Modulation of plasma antidiuretic hormone levels does not change the magnitude of
      the LPS-induced febrile response in Pekin ducks.
AB  - The objective of this study was to determine the effect of modulating the plasma
      concentrations of the avian antidiuretic hormone, arginine vasotocin (AVT), upon
      the febrile response to lipopolysaccharide (LPS) in Pekin ducks. LPS,
      intravenously administered into conscious control birds at a dose of 1 microg x
      kg(-1), caused a monophasic increase in body temperature of 0.85 +/- 0.12 degrees
      C associated with a Thermal Response Index of 2.5 +/- 0.6 C degrees h. Plasma AVT
      concentrations in the control birds also increased with the progression of the
      fever response, more than doubling from their basal values. Ducks in which the
      circulating level of AVT had either been elevated by the intravenous infusion of
      the peptide or dehydration, or reduced by the administration of a specific AVT
      antibody prior to LPS administration, produced body temperature profiles and
      Thermal Response Index values that did not differ significantly from those of the
      control birds. The lack of any direct effect of variations in plasma AVT
      concentrations upon the magnitude of the fever response indicates that the LPS
      induced elevation in plasma AVT is not associated with modulating the rise in
      body temperature obtained in avian fever.

PMID- 10935521
TI  - Anoxia tolerance of con-familial tiger beetle larvae is associated with
      differences in energy flow and anaerobiosis.
AB  - In this study, we compared survivorship, heat dissipation and biochemical
      features of anaerobiosis of two tiger beetle species (Coleoptera: Cicindelidae)
      exposed to anoxia. One species commonly experiences environmental immersion from
      rainfall and snowmelt (Cicindela togata), and the habitat of the other
      (Amblycheila cylindriformis) is not prone to flooding. The ancestral genus, A.
      cylindriformis, survives anoxia for only 2 days at 25 degrees C. In response to
      anoxia, these larvae immediately lose locomotory abilities, tissue concentrations
      of ATP fall precipitously within 12 h, and significant amounts of lactate are
      quickly produced. In contrast, C. togata larvae tolerate anoxia for 5 days. Heat
      dissipation is downregulated to a greater degree than that seen in A.
      cylindriformis (3.4% versus 14% of standard normoxic rate, respectively), the
      ability for locomotion is maintained and normoxic levels of ATP are defended for
      at least 24 h. Lactate is not accumulated until well into anoxic bout, and
      significant amounts of alanine are also produced. This study provides evidence
      that tiger beetles differ in physiological responses to anoxia, and that these
      differences are correlated with flooding risk and with species distribution.

PMID- 10935523
TI  - Cold acclimation and cryoprotectants in a freeze-tolerant Antarctic nematode,
      Panagrolaimus davidi.
AB  - Panagrolaimus davidi is a freeze-tolerant Antarctic nematode which survives
      extensive intracellular freezing. This paper describes the development of culture
      techniques which provide clean samples, with a high degree of freeze tolerance
      and in sufficient quantities for the analysis of potential cryoprotectants.
      Cultures grown at 20 degrees C survived a short-term freezing stress but survival
      declined with the time spent frozen. Acclimation of cultures at 5 degrees C
      enhanced the long-term survival of freezing. Starvation, however, reduced the
      nematode's ability to survive short-term freezing. The principal cryoprotectants
      detected by gas chromatography were trehalose and glycerol. The levels of
      trehalose, but not those of glycerol, increased significantly after acclimation.
      Trehalose may stabilise membranes and protect them against the dehydrating
      effects of the osmotic stresses resulting from freeze concentration effects but
      other factors, such as recrystallisation inhibition, may be involved in long-term
      survival.

PMID- 10935520
TI  - Intracellular calcium and the relationship to contractility in an avian model of
      heart failure.
AB  - Global contractile heart failure was induced in turkey poults by furazolidone
      feeding (700 ppm). Abnormal calcium regulation appears to be a key factor in the
      pathophysiology of heart failure, but the cellular mechanisms contributing to
      changes in calcium fluxes have not been clearly defined. Isolated ventricular
      myocytes from non-failing and failing hearts were therefore used to determine
      whether the whole heart and ventricular muscle contractile dysfunctions were
      realized at the single cell level. Whole cell current- and voltage-clamp
      techniques were used to evaluate action potential configurations and L-type
      calcium currents, respectively. Intracellular calcium transients were evaluated
      in isolated myocytes with fura-2 and in isolated left ventricular muscles using
      aequorin. Action potential durations were prolonged in failing myocytes, which
      correspond to slowed cytosolic calcium clearing. Calcium current-voltage
      relationships were normal in failing myocytes; preliminary evidence suggests that
      depressed transient outward potassium currents contribute to prolonged action
      potential durations. The number of calcium channels (as measured by radioligand
      binding) were also similar in non-failing and failing hearts. Isolated
      ventricular muscles from failing hearts had enhanced inotropic responses, in a
      dose-dependent fashion, to a calcium channel agonist (Bay K 8644). These data
      suggest that changes in intracellular calcium mobilization kinetics and longer
      calcium-myofilament interaction may be able to compensate for contractile
      failure. We conclude that the relationship between calcium current density and
      sarcoplasmic reticulum calcium release is a dynamic process that may be altered
      in the setting of heart failure at higher contraction rates.

PMID- 10935524
TI  - Hemolymph ion composition and volume changes in the supralittoral isopod Ligia
      pallasii Brandt, during molt.
AB  - We analyzed ion composition and volume of the hemolymph of Ligia pallasii in four
      different stages of the molt cycle using capillary electrophoresis and 3H-inulin.
      The main ions in the hemolymph were Na+, K+, Mg2+ , Ca2+, and Cl-. The Ca2+
      concentration increased significantly during the molt by 47% from intermolt to
      intramolt and by 37% from intermolt to postmolt, probably due to resorption of
      Ca2+ from the cuticle and sternal CaCO3 deposits. The K+ concentration increased
      significantly by 20% during molt. The hemolymph volume normalized to the dry mass
      of the animals decreased by 36% from intermolt to late premolt. This was due to a
      reduction in the hemolymph volume and to an increase in dry mass of the animals
      during premolt. A sudden increase in the hemolymph volume occurring between late
      premolt and intramolt served to expand the cuticle. Since the Na+, K+, Mg2+, and
      Cl- concentrations did not change significantly from late premolt to intramolt,
      the increase in hemolymph volume suggests an uptake of seawater rather than
      freshwater.

PMID- 10935525
TI  - Role of Na+/H+ exchange and HCO3- transport in pHi recovery from intracellular
      acid load in cultured epithelial cells of sheep rumen.
AB  - This study sought to investigate effects of short-chain fatty acids and CO2 on
      intracellular pH (pHi) and mechanisms that mediate pHi recovery from
      intracellular acidification in cultured ruminal epithelial cells of sheep. pHi
      was studied by spectrofluorometry using the pH-sensitive fluorescent indicator
      2',7'-bis (carboxyethyl)-5(6')-carboxyfluorescein acetoxymethyl ester (BCECF/AM).
      The resting pHi in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)
      buffered solution was 7.37 +/- 0.03. In HEPES-buffered solution, a NH4+/NH3
      prepulse (20 mM) or addition of butyrate (20 mM) led to a rapid intracellular
      acidification (P < 0.05). Addition of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA: 10
      microM) or HOE-694 (200 microM) inhibited pHi recovery from an NH4+/NH3-induced
      acid load by 58% and 70%, respectively. pHi recovery from acidification by
      butyrate was reduced by 62% and 69% in the presence of EIPA (10 microM) and HOE
      694 (200 microM), respectively. Changing from HEPES-(20 mM) to CO2/HCO3(-)
      buffered (5%/20 mM) solution caused a rapid decrease of pHi (P < 0.01), followed
      by an effective counter-regulation. 4,4'-diisothiocyanatostilbene-2,2'-disulfonic
      acid (DIDS; 100 microM) blocked the pHi recovery by 88%. The results indicate
      that intracellular acidification by butyrate and CO2 is effectively counter
      regulated by an Na+/H+ exchanger and by DIDS-sensitive, HCO3(-)-dependent
      mechanism(s). Considering the large amount of intraruminal weak acids in vivo,
      both mechanisms are of major importance for maintaining the pHi homeostasis of
      ruminal epithelial cells.

PMID- 10935526
TI  - Ramipril increases the protein level of skeletal muscle IRS-1 and alters protein
      tyrosine phosphatase activity in spontaneously hypertensive rats.
AB  - To investigate mechanisms by which angiotensin converting enzyme (ACE)-inhibition
      increases insulin sensitivity, spontaneously hypertensive (SH) rats were treated
      with or without ramipril (1 mg/kg per day) for 12 weeks. Insulin binding and
      protein levels of insulin receptor substrate-1 (IRS-1), p85-subunit of
      phosphatidylinositol 3'-kinase (p85) and Src homology 2 domain-containing
      phosphatase-2 (SHP2) were then determined in hindlimb muscle and liver.
      Additionally, protein tyrosine phosphatase (PTPase) activities towards
      immobilized phosphorylated insulin receptor or phosphorylated IRS-1 of membrane
      (MF) and cytosolic fractions (CF) of these tissues were measured. Ramipril
      treatment increased IRS-1-protein content in muscle by 31+/-9% (P<0.05). No
      effects were observed on IRS-1 content in liver or on insulin binding or protein
      expression of p85 or SHP2 in both tissues. Ramipril treatment also increased
      dephosphorylation of insulin receptor by muscle CF (22.0+/-1.0%/60 min compared
      to 16.8+/-1.5%/60 min; P<0.05), and of IRS-1 by liver MF (37.2+/-1.7%/7.5 min
      compared to 33.8+/-1.7%/7.5 min; P<0.05) and CF (36.8+/-1.0%/7.5 min compared to
      33.2+/-1.0%/7.5 min; P<0.05). We conclude that the observed effects of ACE
      inhibition by ramipril on the protein expression of IRS-1 and on PTPase activity
      might contribute to its effect on insulin sensitivity.

PMID- 10935527
TI  - Comparison of the protective effects of ischemic preconditioning and the Na+/H+
      exchanger blockade.
AB  - The protective effects of ischemic preconditioning (IP) and Na+/H+ exchanger
      blockade (NHEb) by two blockers [ethylisopropylamiloride (EIPA) and HOE 642] were
      compared in the isovolumic perfused rat heart. The impairment in systolic and
      diastolic function detected in control ischemic hearts (C) exposed to 20 min of
      ischemia and 30 min of reperfusion was diminished in similar extent by IP and by
      NHEb with EIPA and HOE 642. At the end of the reperfusion period +dP/dtmax values
      were 57+/-9% in C hearts and 94+/-6%, 82+/-6% and 104+/-6% after IP and NHEb with
      EIPA and HOE 642, respectively. A depletion of ATP levels detected in C hearts
      after reperfusion (from 20.2+/-0.8 micromol/g dry weight before ischemia to 6.9+/
      0.7 micromol/g dry weight) was partially prevented by both IP and NHEb with EIPA
      (9.2+/-0.7 micromol/g dry weight and 11.1+/-0.5 micromol/g dry weight,
      respectively). The ischemic contracture (IC), assessed by the left ventricular
      end diastolic pressure (LVEDP), observed in C hearts (35+/-4 mmHg) was not
      decreased by IP (40+/-4 mmHg) but it was prevented by NHEb (18+/-4 mmHg and 10+/
      3 mmHg with EIPA and HOE 642, respectively). The ATP levels at the end of the
      ischemic period were similar in C and IP hearts (4.1+/-0.2 micromol/g dry wt vs.
      3.3+/-0.4 micromol/g dry wt) but they were significantly higher after NHEb with
      HOE 642 (7.0+/-1.0 micromol/g dry wt). PKC inhibition by chelerythrine abolished
      the protection induced by IP after reperfusion although not the improvement
      induced by NHEb with EIPA. According to the present results, we can conclude that
      despite the fact that IP and NHEb are protecting the postischemic function in a
      similar magnitude, both interventions are different in terms of modifying IC that
      develops during the ischemic period. IC was prevented by NHEb whereas it was not
      by IP. Furthermore, IP protection and not that obtained by NHEb is abolished by
      PKC.

PMID- 10935528
TI  - Ca2+ oscillation and c-fos gene expression induced via muscarinic acetylcholine
      receptor in human T- and B-cell lines.
AB  - We previously reported that blood acetylcholine (ACh) mainly originates from T
      lymphocytes and that muscarinic (Ms) ACh receptor mRNA is expressed in both T-
      and B-lymphocytes. In the present study, we used confocal laser scanning
      microscopy and fluo-3, a calcium-sensitive indicator, to investigate the effects
      of Ms-ACh receptor agonists on the intracellular free Ca2+ concentration
      ([Ca2+]i) in single cells from human T-cell (CEM) and B-cell (Daudi) lines, which
      we used as models of lymphocytes. In both cell lines, stimulation of Ms-ACh
      receptors with ACh (0.1-100 microM), bethanechol (100 microM), car-bachol (100
      microM) or oxotremorine-M (Oxo-M; 0.1-100 microM) induced [Ca2+]i-dependent
      increases in fluo-3 fluorescence, which in the presence of extracellular Ca2+
      were followed by oscillations in [Ca2+]i that persisted for at least 10 min. All
      effects were completely blocked by atropine (1 microM), an Ms-ACh receptor
      antagonist. In both cell lines Oxo-M (100 microM) up-regulated expression of c
      fos mRNA in an extracellular Ca2+-dependent manner. Again, the effect was blocked
      by 1 microM atropine. These results provide the first evidence that stimulation
      of Ms-ACh receptors induces Ca2+ oscillations and up-regulates c-fos gene
      expression in T- and B-lymphocytes, which is consistent with the notion that ACh
      released from T-lymphocytes triggers nuclear signaling via Ms-ACh receptors.

PMID- 10935529
TI  - Effects of antiarrhythmic drugs on cloned cardiac voltage-gated potassium
      channels expressed in Xenopus oocytes.
AB  - The effects of 17 commonly used antiarrhythmic drugs on the rapidly activating
      cardiac voltage-gated potassium channels (Kv1.1, Kv1.2, Kv1.4, Kv1.5, Kv2.1 and
      Kv4.2) were studied in the expression system of the Xenopus oocyte. A systematic
      overview on basic properties was obtained using a simple and restricted
      experimental protocol (command potentials 10 mV and 50 mV positive to the
      threshold potential; concentration of 100 micromol/l each). The study revealed
      that 8 of 17 drugs yielded significant effects (changes >10% of control) on at
      least one type of potassium channel in the oocyte expression system. These drugs
      were ajmaline, diltiazem, flecainide, phenytoin, propafenone, propranolol,
      quinidine and verapamil, whereas the effects of adenosine, amiodarone, bretylium,
      disopyramide, lidocaine, mexiletine, procainamide, sotalol and tocainide were
      negligible. The drug effects were characterized by reductions of the potassium
      currents (except for quinidine and ajmaline). A voltage-dependence of drug effect
      was found for quinidine, verapamil and diltiazem. The different effect of the
      drugs was not related to the fast or slow current inactivation of the potassium
      channels (except for verapamil). Profiles of the individual drug effects at the
      different potassium channel types were identical for propafenone and flecainide
      and differed for all other substances. The study demonstrates marked differences
      in sensitivity to antiarrhythmic drugs within the group of voltage-operated
      cardiac potassium channel types. Taking the restrictions of the oocyte system
      into consideration, the findings suggest that several antiarrhythmic drugs exert
      significant effects at rapidly activating cardiac potassium channels.

PMID- 10935530
TI  - Characterization of opioid receptor types modulating acetylcholine release in
      septal regions of the rat brain.
AB  - Presynaptic opioid receptors of the delta- and mu-types have been shown to
      inhibit the release of acetylcholine (ACh) in the rat striatum and hippocampus,
      respectively, but it is unknown whether opioid receptors modulate the release of
      ACh also in the region of origin of the hippocampal cholinergic innervation, the
      septum. To answer this question, slices (350 microm) of the medial septal area
      and of the diagonal band of Broca, as well as (for comparison) of the
      hippocampus, were prepared from adult male Wistar rats. The slices were incubated
      with [3H]choline, superfused in the presence of hemicholinium-3 (10 microM) and
      stimulated twice (S1, S2) by electrical fields (360 pulses, 3 Hz, 2 ms, 60 mA);
      opioid receptor agonists were present during S2. The preferential mu-agonist [D
      Ala2,N-Me-Phe4,Gly-ol5]enkephalin (DAMGO) inhibited the evoked ACh release by
      maximally about 40% in hippocampal slices and acted even more strongly in the
      medial septal area, or the diagonal band of Broca (about 60% or 75% maximal
      inhibition, respectively). These effects were reduced or abolished by the
      preferential mu-antagonist naloxone, which showed no effects when given alone.
      Using naloxone in the presence of a cocktail of peptidase inhibitors, no evidence
      for an endogenous tone of opioid peptides was found in the medial septal area,
      diagonal band of Broca or the hippocampus. Using the preferential delta-agonist
      [D-Pen2, D-Pen5]enkephalin (DPDPE) and the delta-antagonist naltrindole, a delta
      opioid receptor inhibiting evoked ACh release was clearly detectable both in the
      medial septal area and the diagonal band of Broca, but not in the hippocampus,
      whereas the preferential kappa-agonist trans-3,4-dichloro-N-methyl-N-[2(1
      pyrrolidinyl)cyclo-hexyl] benzeneacetamide (U50,488H) had only weak or no
      effects. In addition to the functional experiments, double in-situ hybridization
      studies were performed, in which cells containing mRNA for choline
      acetyltransferase (ChAT) were labeled by an antibody-linked enzymatic staining
      procedure, whereas mRNAs for mu- or delta-opioid receptors were detected with
      radioactive probes. These experiments revealed that in the septal region mainly
      mu-opioid receptors were expressed by neurons positive for ChAT mRNA, whereas in
      the rat striatum the expression of delta-opioid receptors prevailed in those
      neurons. We conclude that in the septal area of the rat brain, in contrast to the
      rat striatum and hippocampus, both presynaptic mu- and delta-opioid receptors
      modulate the evoked release of ACh. Whether presynaptic mu- and delta-opioid
      receptors occur on the same or on different septal cells or axon terminals
      remains to be clarified.

PMID- 10935531
TI  - Nicotine inhibits firing activity of dorsal raphe 5-HT neurones in vivo.
AB  - It is established that the brain monoaminergic systems are among the main targets
      of several dependence-inducing drugs, including nicotine. In the present study
      extracellular electrophysiological recordings were performed to investigate the
      effects of nicotine on dorsal raphe 5-HT neurones. Nicotine, administered
      systemically (50-400 microg/kg, i.v.) in chloral hydrate-anaesthetised rats,
      induced a transient inhibition of the majority of 5-HT neurones recorded (38 of
      45). The inhibition was rapid in onset (about 30 s) and the firing rate returned
      to baseline within 1-3 min. No apparent tachyphylaxis was observed to this
      inhibitory effect. The centrally acting nicotine antagonist mecamylamine (4
      mg/kg, i.v.), but not the peripherally acting nicotine antagonist chlorisondamine
      (0.3 mg/kg, i.v.) antagonised the nicotine-induced inhibition of 5-HT neurones.
      The inhibition of 5-HT neurones was also blocked with a selective 5-HT1A receptor
      antagonist (WAY 100635; 0.1 mg/kg, i.v.), indicating a possible involvement of
      somato-dendritic 5-HT1A receptors in the effect of nicotine. Interestingly,
      microiontophoretic application of nicotine into the dorsal raphe failed to
      inhibit 5-HT neurones, suggesting an indirect effect of nicotine on 5-HT
      neurones, possibly involving afferent pathways.

PMID- 10935532
TI  - Inhibition of glucose-induced insulin secretion by a peripheral-type
      benzodiazepine receptor ligand (PK11195).
AB  - We have recently shown that benzodiazepines with high affinity for peripheral
      type receptors such as 4'-chlordiazepam inhibit insulin secretion in vitro. PK
      11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxami
      de], a potent and selective ligand for peripheral benzodiazepine binding sites,
      was also shown to inhibit insulin release from rat pancreatic islets. Both
      substances have been reported to interact with mitochondrial binding sites.
      Hence, the present study was performed to investigate the effects of PK 11195 on
      insulin secretion induced by either a metabolic or a non-metabolic stimulus. In
      the rat isolated pancreas perfused at a constant pressure with a Krebs
      bicarbonate buffer containing a slightly stimulating glucose concentration (8.3
      mM), PK 11195 (10(-7)-10(-5) M) induced a progressive and concentration-dependent
      decrease in insulin secretion. Simultaneously, we recorded the effects on the
      pancreatic flow rate; in contrast to 4'-chlordiazepam, previously shown to induce
      vasodilation in the same preparation, PK 11195 was ineffective. The differential
      effects of these two substances on vascular resistance and insulin secretion may
      suggest the existence of different subtypes of peripheral benzodiazepine
      receptors on pancreatic beta-cells and vessels. A metabolic stimulation of
      insulin secretion was induced by a glucose increment from 4.2 mM to 8.4 mM or by
      2 mM alpha-ketoisocaproic acid (KIC), which is directly metabolized in the
      mitochondria; these stimulations could be reduced by 10(-5) M PK 11195 (P<0.05).
      In contrast, the drug was ineffective on the insulin secretion induced by 5 mM or
      10 mM KCl in the presence of a nonstimulating glucose concentration (4.2 mM).
      These results suggest that PK 11195 inhibits insulin secretion by interfering
      with mitochondrial oxidative metabolism.

PMID- 10935533
TI  - Altered endothelium-dependent and -independent hyperpolarization and endothelium
      dependent relaxation in carotid arteries isolated from streptozotocin-induced
      diabetic rats.
AB  - We examined endothelium-dependent and -independent hyperpolarizations and
      endothelium-dependent relaxation responses in carotid arteries isolated from
      streptozotocin-induced diabetic rats and age-matched controls. The resting
      membrane potentials were not significantly different between control and diabetic
      carotid arteries. The endothelium-dependent hyperpolarization induced by
      acetylcholine, which was inhibited by TEA but not by glibenclamide or by
      treatment with either a high concentration of glucose or pertussis toxin, was
      significantly weaker in diabetic arteries than in the controls. The relaxation
      responses to acetylcholine in carotid artery rings were significantly decreased
      in streptozotocin-diabetic rats. Treatment with NG-nitro-L-arginine (L-NOARG)
      inhibited the acetylcholine-induced maximal relaxation by 80% and 30% in control
      and streptozotocin-diabetic rats, respectively, and the simultaneous application
      of L-NOARG and indomethacin had a more potent inhibitory effect on this
      relaxation in both groups. The release of 6-keto-prostaglandin F1alpha and that
      of thromboxane A2 in response to methoxamine or methoxamine plus acetylcholine
      were both markedly decreased in diabetic rats. The cromakalim-induced
      hyperpolarization of the carotid artery, which was completely prevented by
      glibenclamide, was also significantly weaker in diabetic arteries than in the
      controls. These results suggest that changes in (1) various K+ channels on smooth
      muscle, (2) the biosynthesis of cyclooxygenase products and (3) endothelium
      dependent relaxation may be important factors in the development of diabetic
      complications in the carotid artery.

PMID- 10935534
TI  - Characterization of histamine H3 receptors in mouse brain using the H3 antagonist
      [125I]iodophenpropit.
AB  - We have characterized the binding of the histamine H3 receptor antagonist
      [125I]iodophenpropit to mouse brain. [125I]Iodophenpropit saturably bound to
      mouse brain membranes with a pKd-value of 9.31+/-0.04 nM and a receptor binding
      density of 290+/-8 fmol per mg protein. Saturation binding analysis revealed
      binding of [125I]iodophenpropit to a single class of sites, showing linear
      Scatchard plots and Hill coefficients not different from unity (nH=0.98+/-0.02).
      At a concentration of 0.25 nM [125I]iodophenpropit, specific binding represented
      about 75% of the total binding. Competition binding curves for H3 receptor
      antagonists were fitted best to a one-site model, showing pKi-values in general
      accordance with the pA2-values obtained in mouse cerebral cortex. Displacement of
      [125I]iodophenpropit by the H3 receptor agonists (R)-alpha-methylhistamine,
      immepip, imetit and histamine were fitted best to a two-site model. Competition
      binding curves of (R)-alpha-methylhistamine showed a rightward shift upon
      incubation with GTPgammaS (10 microM), indicating the involvement of G-proteins
      in H3 agonist binding. In contrast, competition binding curves of the antagonists
      iodophenpropit, thioperamide and burimamide were not affected by GTPgammaS (10
      microM). Autoradiographic experiments showed that [125I]iodophenpropit binding
      sites were heterogeneously distributed, similarly to the distribution of
      histamine H3 receptors reported in rat brain. Highest densities were observed in
      the cerebral cortex, the striatum, the nucleus accumbens, the globus pallidus and
      the substantia nigra. In conclusion, we have demonstrated that in mouse brain,
      [125I]iodophenpropit selectively binds to histamine H3 receptors. We also
      observed that the mouse brain H3 receptors labelled by [125I]iodophenpropit
      displayed binding characteristics and a distribution similar to rat brain.

PMID- 10935535
TI  - Vasodilator effects of KRN2391, levcromakalim and 3-morpholino-sydnonimin in
      human pial and omental arteries.
AB  - The vasodilator action of KRN2391 (10 nM-10 microM), a combined ATP-sensitive
      potassium channel (KATP) opener and organic nitrate, was investigated in human
      pial and omental arteries. Previous animal studies have suggested that opening of
      KATP and activation of guanylate cyclase may contribute to varying extents to the
      vasodilator action of KRN2391, depending on the origin and size of the vascular
      preparation. Vasodilator responses were studied in isolated vascular segments
      (diameter 0.4-0.8 mm) pre-contracted with endothelin-1 in the presence or absence
      of glibenclamide (inhibitor of KATP), LY83583 (inhibitor of guanylate cyclase),
      zaprinast (inhibitor of cyclic GMP phosphodiesterase V) and NG-nitro-L-arginine
      (inhibitor of nitric oxide synthase). KRN2391 induced concentration-dependent
      vasodilator responses of similar potency in arteries from the two vascular
      regions. While glibenclamide (1 microM) had no effect in omental arteries, this
      compound produced a tenfold rightwards shift of the concentration-response curve
      for KRN2391 in pial arteries without affecting the maximal response (Emax).
      LY83583 (10 microM), zaprinast (10 microM) and NG-nitro-L-arginine (0.1 mM) all
      failed to affect the vasodilator responses to KRN2391 significantly in either
      artery. However, in ring segments of rat aorta LY83583 displaced the
      concentration-response curve for the nitric oxide donor 3-morpholino-sydnonimin
      (10 nM-0.1 mM) to the right, while zaprinast produced a leftwards shift. The
      prototype KATP opener levcromakalim (0.01-10 microM) elicited a larger relaxation
      in pial (Emax 80+/-6%) than in omental (Emax 47+/-13%) arteries, whereas 3
      morpholino-sydnonimin produced a smaller relaxation in pial (Emax 50+/-18%) than
      in omental (Emax 90+/-4%) arteries. These results suggest that the vasodilator
      response to KRN2391 is mediated by KATP in human cerebral arteries, but dependent
      on neither KATP nor guanylate cyclase in human omental arteries. The results with
      levcromakalim and 3-morpholino-sydnonimin indicate that opening of KATP may be a
      more effective mechanism of vasodilatation in pial than in omental arteries from
      man, whereas the reverse appears to be true for guanylate cyclase activation.

PMID- 10935536
TI  - Gabapentin-lactam (8-aza-spiro[5,4]decan-9-on; GBP-L) inhibits oxygen glucose
      deprivation-induced [3H]glutmate release and is a neuroprotective agent in amodel
      of acute retinal ischemia.
AB  - The modulation of the enhanced release of [3H]glutamate following ischemia-like
      conditions was studied in rat hippocampal slices using a superfusion system.
      Ischemia was simulated by a glucose-free medium equilibrated with 95% N2 and 5%
      CO2. In this model the potential neuroprotective effects of several substances on
      [3H]glutamate release induced by ischemia-like conditions were investigated.
      Gabapentin-lactam (8-aza-spiro-5,4-decan-9-on; GBP-L) was synthesised and
      patented in our laboratory. GBP-L (100 microM) reduced the oxygen glucose
      deprivation-induced [3H]glutamate release by 42.5%, CI95=[33.4%, 51.5%]. The KATP
      channel antagonist glibenclamide (1 microM) blocked this effect completely. The
      high antagonist potency was reflected by an apparent pA2-value of glibenclamide
      of 8.3, CI95=[6.8, 9.4]. Minoxidil sulfate (10 microM), a KATP channel opener,
      mimicked the effect of GBP-L (inhibition by 22.8%, CI95=[13.2%, 32.5%]).
      Similarly to its lactam, also gabapentin (100 microM) reduced the oxygen glucose
      deprivation-induced [3H]glutamate release by 30.6%, CI95=[15.5%, 45.7%], whereas
      the "antiglutamatergic" drug riluzole was ineffective. GBP-L and gabapentin were
      also tested in an in vivo model of acute retinal ischemia in rats. The
      intraocular pressure was elevated for 1 h above the systolic blood pressure. In
      the control group, 17.5%, CI95=[13%, 22%], of retinal ganglion cells had survived
      after 2 weeks. GBP-L doubled the number of surviving ganglion cells up to 35%,
      CI95=[27%, 43%], while gabapentin had no effect. This difference between
      gabapentin and its lactam may be due to different pharmacokinetic properties: In
      contrast to the gamma-amino acid gabapentin, GBP-L is uncharged and therefore
      might diffuse more easily through biological membranes, e.g. the plasma membrane,
      to get access to an intracellular locus of action. Thus, the neuroprotective
      properties in vivo and the diminished oxygen glucose deprivation-induced
      [3H]glutamate efflux in vitro of the presumed KATP channel agonist GBP-L suggest
      that this substance might be therapeutically applied in pathological situations
      induced by a rise in extracellular glutamate and/or neuronal cell death.

PMID- 10935538
TI  - Chronic elevation of calmodulin in the ventricles of transgenic mice increases
      the autonomous activity of calmodulin-dependent protein kinase II, which
      regulates atrial natriuretic factor gene expression.
AB  - Although isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have
      been implicated in the regulation of gene expression in cultured cells, this
      issue has yet to be addressed in vivo. We report that the overexpression of
      calmodulin in ventricular myocytes of transgenic mice results in an increase in
      the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin
      transgene is regulated by a 500-bp fragment of the atrial natriuretic factor
      (ANF) gene promoter which, based on cell transfection studies, is itself known to
      be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the
      activity of the transgene and establishes a positive feed-forward loop, which
      also extends the temporal expression of the endogenous ANF promoter in
      ventricular myocytes. Both the increased activity of CaMKII and transcriptional
      activation of ANF are highly selective responses to the chronic overexpression of
      calmodulin. These results indicate that CaMKII can regulate gene expression in
      vivo and suggest that this enzyme may represent the Ca2+-dependent target
      responsible for reactivation of the ANF gene during ventricular hypertrophy.

PMID- 10935537
TI  - Studies on the cytotoxic mechanisms of ginkgetin in a human ovarian
      adenocarcinoma cell line.
AB  - The cytotoxic effects of ginkgetin, a natural biflavone isolated from Selaginella
      moellendorffii Hieron, were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) assay in three different human cell lines:
      ovarian adenocarcinoma (OVCAR-3), cervical carcinoma (HeLa) and foreskin
      fibroblast (FS-5). The concentrations of ginkgetin required to induce 50% death
      (EC50) in OVCAR-3, HeLa, and FS-5 were 3.0, 5.2, and 8.3 microg/ml, respectively.
      Morphological changes in cells and their nuclei, DNA fragmentation with a
      characteristic pattern of inter-nucleosomal ladder, and double-stranded DNA
      breaks were detected following treatment with 3 microg/ml of this biflavone for
      24 h. Incubation with 5 microg/ml ginkgetin led to increased intracellular levels
      of hydrogen peroxide as early as 30 min. The cytotoxicity of ginkgetin was
      partially inhibited by pretreating cells with vitamin C, vitamin E or catalase.
      Catalase not only afforded the best protective effect among three antioxidants,
      but also reduced both the DNA fragmentation and double-stranded DNA breakage
      induced by ginkgetin. Moreover, the involvement of caspase(s) in ginkgetin
      induced apoptosis was demonstrated by the activation of caspase 3 after drug
      treatment and the suppression of cell death by a broad-spectrum caspase
      inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk). However,
      the protective effects of z-VAD-fmk and catalase were not additive. Taken
      together, our results indicated that the apoptosis induced by ginkgetin
      (especially at 5 microg/ml) is mediated mainly through the activation of
      caspase(s) by the hydrogen peroxide generated possibly through autooxidation of
      this biflavone.

PMID- 10935539
TI  - Pituitary tumor transforming gene (PTTG) regulates placental JEG-3 cell division
      and survival: evidence from live cell imaging.
AB  - The pituitary transforming gene, PTTG, is abundantly expressed in endocrine
      neoplasms. PTTG has recently been recognized as a mammalian securin based on its
      biochemical homology to Pds1p. PTTG expression and intracellular localization
      were therefore studied during the cell cycle in human placental JEG-3 cells. PTTG
      mRNA and protein expressions were low at the G1/S border, gradually increased
      during S phase, and peaked at G2/M, but PTTG levels were attenuated as cells
      entered G1. In interphase cells, wild-type PTTG, an epitope-tagged PTTG, and a
      PTTG-EGFP conjugate all localized to both the nucleus and cytoplasm, but in
      mitotic cells, PTTG was not observed in the chromosome region. PTTG-EGFP
      colocalized with mitotic spindles in early mitosis and was degraded in anaphase.
      Intracellular fates of PTTG-EGFP and a conjugate of EGFP and a mutant inactivated
      PTTG devoid of an SH3-binding domain were observed by real-time visualization of
      the EGFP conjugates in live cells. The same cells were continuously observed as
      they progressed from G1/S border to S, G2/M, and G1. Most cells (67%) expressing
      PTTG-EGFP died by apoptosis, and few cells (4%) expressing PTTG-EGFP divided,
      whereas those expressing mutant PTTG-EGFP divided. PTTG-EGFP, as well as the
      mutant PTTG-EGFP, disappeared after cells divided. The results show that PTTG
      expression and localization are cell cycle-dependent and demonstrate that PTTG
      regulates endocrine tumor cell division and survival.

PMID- 10935540
TI  - Dysregulation of EGF family of growth factors and COX-2 in the uterus during the
      preattachment and attachment reactions of the blastocyst with the luminal
      epithelium correlates with implantation failure in LIF-deficient mice.
AB  - Various mediators, including cytokines, growth factors, homeotic gene products,
      and prostaglandins (PGs), participate in the implantation process in an
      autocrine, paracrine, or juxtacrine manner. However, interactions among these
      factors that result in successful implantation are not clearly understood.
      Leukemia inhibitory factor (LIF), a pleiotropic cytokine, was shown to be
      expressed in uterine glands on day 4 morning before implantation and is critical
      to this process in mice. However, the mechanism by which LIF executes its effects
      in implantation remains unknown. Moreover, interactions of LIF with other
      implantation-specific molecules have not yet been defined. Using normal and
      delayed implantation models, we herein show that LIF is not only expressed in
      progesterone (P4)-primed uterine glands before implantation in response to
      nidatory estrogen, it is also induced in stromal cells surrounding the active
      blastocyst at the time of the attachment reaction. This suggests that LIF has
      biphasic effects: first in the preparation of the receptive uterus and
      subsequently in the attachment reaction. The mechanism by which LIF participates
      in these events was addressed using LIF-deficient mice. We observed that while
      uterine cell-specific proliferation, steroid hormone responsiveness, and
      expression patterns of several genes are normal, specific members of the EGF
      family of growth factors, such as amphiregulin (Ar), heparin-binding EGF-like
      growth factor (HB-EGF), and epiregulin, are not expressed in LIF(-/-) uteri
      before and during the anticipated time of implantation, although EGF receptor
      family members (erbBs) are expressed correctly. Furthermore, cyclooxygenase-2
      (COX-2), an inducible rate-limiting enzyme for PG synthesis and essential for
      implantation, is aberrantly expressed in the uterus surrounding the blastocyst in
      LIF(-/-) mice. These results suggest that dysregulation of specific EGF-like
      growth factors and COX-2 in the uterus contributes, at least partially, to
      implantation failure in LIF(-/-) mice. Since estrogen is essential for uterine
      receptivity, LIF induction, and blastocyst activation, it is possible that the
      nidatory estrogen effects in the P4-primed uterus for implantation are mediated
      via LIF signaling. However, we observed that LIF can only partially resume
      implantation in P4-primed, delayed implanting mice in the absence of estrogen,
      suggesting LIF induction is one of many functions that are executed by estrogen
      for implantation.

PMID- 10935541
TI  - Dynamics of intracellular movement and nucleocytoplasmic recycling of the ligand
      activated androgen receptor in living cells.
AB  - An expression construct containing the cDNA encoding a modified aequorea green
      fluorescent protein (GFP) ligated to the 5'-end of the rat androgen receptor (AR)
      cDNA (GFP-AR) was used to study the intracellular dynamics of the receptor
      movement in living cells. In three different cell lines, ie. PC3, HeLa, and COS1,
      unliganded GFP-AR was seen mostly in the cytoplasm and rapidly (within 15-60 min)
      moved to the nuclear compartment after androgen treatment. Upon androgen
      withdrawal, the labeled AR migrated back to the cytoplasmic compartment and
      maintained its ability to reenter the nucleus on subsequent exposure to androgen.
      Under the condition of inhibited protein synthesis by cycloheximide (50
      microg/ml), at least four rounds of receptor recycling after androgen treatment
      and withdrawal were recorded. Two nonandrogenic hormones, 17beta-estradiol and
      progesterone at higher concentrations (10(-7)/10(-6) M), were able to both
      transactivate the AR-responsive promoter and translocate the GFP-AR into the
      nucleus. Similarly, antiandrogenic ligands, cyproterone acetate and casodex, were
      also capable of translocating the cytoplasmic AR into the nucleus albeit at a
      slower rate than the androgen 5alpha-dihydrotestosterone (DHT). All AR ligands
      with transactivation potential, including the mixed agonist/antagonist
      cyproterone acetate, caused translocation of the GFP-AR into a subnuclear
      compartment indicated by its punctate intranuclear distribution. However,
      translocation caused by casodex, a pure antagonist, resulted in a homogeneous
      nuclear distribution. Subsequent exposure of the casodex-treated cell to DHT
      rapidly (15-30 min) altered the homogeneous to punctate distribution of the
      already translocated nuclear AR. When transported into the nucleus either by
      casodex or by DHT, GFP-AR was resistant to 2 M NaCl extraction, indicating that
      the homogeneously distributed AR is also associated with the nuclear matrix.
      Taken together, these results demonstrate that AR requires ligand activation for
      its nuclear translocation where occupancy by only agonists and partial agonists
      can direct it to a potentially functional subnuclear location and that one
      receptor molecule can undertake multiple rounds of hormonal signaling; this
      indicates that ligand dissociation/inactivation rather than receptor degradation
      may play a critical role in terminating hormone action.

PMID- 10935542
TI  - Role of cyclophilin B in prolactin signal transduction and nuclear
      retrotranslocation.
AB  - The pleiotropic actions of PRL are necessary for mammary growth and
      differentiation and in vitro lymphoid proliferation. The proximal action of this
      ligand is mediated by its cell surface receptor via associated networks. PRL
      action, however, is also associated with the internalization and translocation of
      this hormone into the nucleus. To delineate the mechanism of this
      retrotranslocation, a yeast two-hybrid screen was performed and revealed an
      interaction between PRL and cyclophilin B (CypB). CypB is a peptidyl prolyl
      isomerase (PPI) found in the endoplasmic reticulum, extracellular space, and
      nucleus. The interaction between CypB and PRL was subsequently confirmed in vitro
      and in vivo through the use of recombinant proteins and coimmunoprecipitation
      studies. The exogenous addition of CypB potentiated the 3H-thymidine
      incorporation of PRL-dependent cell lines up to 18-fold. CypB by itself was
      nonmitogenic and did not potentiate the action of GH or other interleukins. CypB
      did not alter the affinity of the PRL receptor (PRLr) for its ligand, or increase
      the phosphorylation of PRLr-associated Jak2 or Stat5a. The potentiation of PRL
      action by CypB, however, was accompanied by a dramatic increase in the nuclear
      retrotranslocation of PRL. A CypB mutant, termed CypB-NT, was generated that
      lacked the wild-type N-terminal nuclear localization sequence. Although CypB-NT
      demonstrated levels of PRL binding and PPI activity equivalent to wild-type CypB,
      it was incapable of mediating the nuclear retrotranslocation of PRL or enhancing
      PRL-driven proliferation. These studies reveal CypB as an important chaperone
      facilitating the nuclear retrotransport and action of the lactogenic hormones.

PMID- 10935543
TI  - Human androgen receptor mutation disrupts ternary interactions between ligand,
      receptor domains, and the coactivator TIF2 (transcription intermediary factor 2).
AB  - The androgen receptor (AR) is a ligand-dependent X-linked nuclear transcription
      factor regulating male sexual development and spermatogenesis. The receptor is
      activated when androgen binds to the C-terminal ligand-binding domain (LBD),
      triggering a cascade of molecular events, including interactions between the LBD
      and the N-terminal transactivation domain (TAD), and the recruitment of
      transcriptional coactivators. A nonconservative asparagine to lysine substitution
      in AR residue 727 was encountered in a phenotypically normal man with
      subfertility and depressed spermatogenesis. This N727K mutation, although located
      in the LBD, did not alter any ligand-binding characteristic of the AR in the
      patient's fibroblasts or when expressed in heterologous cells. Nonetheless, the
      mutant AR displayed only half of wild-type transactivation capacity when exposed
      to physiological or synthetic androgens. This transactivation defect was
      consistently present when examined with two different reporter systems in three
      cell lines, using three androgen-driven promoters (including the complex human
      prostate-specific antigen promoter), confirming the pathogenicity of the
      mutation. In mammalian two-hybrid assays, N727K disrupted LBD interactions with
      the AR TAD and with the coactivator, transcription intermediary factor 2 (TIF2).
      Strikingly, the transactivation defect of the mutant AR can be rectified in vitro
      with mesterolone, consistent with the ability of this androgen analog to restore
      sperm production in vivo. Mesterolone, but not the physiological androgen
      dihydrotestosterone, restored mutant LBD interactions with the TAD and with TIF2,
      when expressed as fusion proteins in the two-hybrid assay. Our data support an
      emerging paradigm with respect to AR mutations in the LBD and male infertility:
      pathogenicity is transmitted through reduced interdomain and coactivator
      interactions, and androgen analogs that are corrective in vitro may indicate
      hormonal therapy.

PMID- 10935544
TI  - Three amino acids specify coactivator choice by retinoid X receptors.
AB  - Binding of agonists to nuclear receptors results in a conformational change in
      receptor structure that promotes interaction between activated receptors and
      coactivators. Receptor-coactivator interactions are mediated by the agonist
      dependent formation of a hydrophobic pocket on the part of receptors, and short
      leucine-rich sequences termed LxxLL motifs or nuclear receptor boxes present in
      coactivators. RXR-PPARgamma (retinoid X receptor-peroxisome proliferator
      activated receptor-gamma) heterodimers play important roles in adipocyte and
      macrophage differentiation and have been implicated as therapeutic targets in
      diabetes, atherosclerosis, and cancer. Analysis of interactions between RXR
      PPARgamma heterodimers and coactivator nuclear receptor boxes suggests that RXR
      and PPARgamma can distinguish among coactivators by recognizing distinct
      structural features of nuclear receptor boxes. The results also indicate that
      coactivator choice by RXR is mediated by three nonconserved amino acids of the
      nuclear receptor box. The ability of an optimized seven-amino acid nuclear
      receptor box to specifically interact with RXR and function as a selective
      inhibitor suggests the coactivator-binding pocket may serve as a new target for
      drug discovery.

PMID- 10935545
TI  - Crucial role of the H11-H12 loop in stabilizing the active conformation of the
      human mineralocorticoid receptor.
AB  - The crystal structures of ligand-free and agonist-associated ligand-binding
      domain (LBD) of nuclear receptors (NRs) reveal that the amphipathic helix H12 is
      folded back toward the LBD core in the agonist-associated conformation, allowing
      the binding of coactivators. We used alanine scanning mutagenesis to explore the
      role of the residues of the loop connecting H11 and H12 in the activation of the
      human mineralocorticoid receptor (hMR), a member of the NRs family. H950A
      retained the ligand binding and transcriptional activities of the wild-type
      receptor and interacted with coactivators. In contrast F956A had no receptor
      functions. Aldosterone bound to the mutant hMRs (L952A, K953A, V954A, E955A,
      P957A) with nearly the same affinity as to the wild-type receptor and caused a
      receptor conformational change in these mutant hMRs as it does for the wild-type
      receptor. But the aldosterone-induced transcriptional activity of the mutant hMRs
      was lower (L952A, E955A, P957A) than that of the wild-type receptor or completely
      abolished (K953A, V954A) and their interaction with coactivators was impaired
      (E955A) or suppressed (L952A, K953A, V954A, P957A). In the light of a hMR-LBD
      model based on the structure of the progesterone-associated receptor-LBD, we
      propose that the integrity of the H11-H12 loop is crucial for folding the
      receptor into a ligand-binding competent state and for establishing the network
      of contacts that stabilize the active receptor conformation.

PMID- 10935546
TI  - CBP (CREB binding protein) integrates NF-kappaB (nuclear factor-kappaB) and
      glucocorticoid receptor physical interactions and antagonism.
AB  - Nuclear factor-kappaB (NF-kappaB) and the glucocorticoid receptor (GR) are
      transcription factors with opposing actions in the modulation of
      immune/inflammatory responses. NF-kappaB induces the expression of
      proinflammatory genes, while GR suppresses immune function in part by suppressing
      expression of the same genes. Previously, we demonstrated that physiological
      antagonism between NF-kappaB and GR is due to a mutual transcriptional antagonism
      that requires the p65 subunit of NF-kappaB and multiple domains of GR (1). To
      elucidate the mechanism(s) of NF-kappaB p65 and GR transcriptional antagonism, we
      analyzed the interactions of wild-type p65 and p65 RHD (rel homology domain, a
      dominant negative mutant of p65 which lacks a transactivation domain) with GR. We
      show that p65RHD blocks p65-mediated transactivation, yet does not block the
      repression of GR transactivation by p65, indicating that transcriptional activity
      by p65 is not required to repress GR function. Both p65 and p65 RHD physically
      interact with GR, but only intact p65 represses GR-mediated signaling,
      implicating the p65 transactivation domain in the transcriptional repression of
      GR. To further characterize p65-GR interactions, we examined the role of the
      transcriptional co-integrator CREB binding protein (CBP) in their mutual
      antagonism. GR-mediated repression of p65 transactivation and p65-mediated
      repression of GR transactivation, as well as the physical interaction between NF
      kappaB and GR, are enhanced by CBP. GR bound to the antagonist RU 486, although
      transcriptionally inactive, retains the ability to repress p65 transactivation.
      However, CBP does not physically interact with antagonist-bound GR and does not
      enhance its repressive effect on p65. These data suggest that CBP functions as an
      integrator of p65/GR physical interaction, rather than as a limiting cofactor for
      which p65 and GR compete.

PMID- 10935547
TI  - Sp1, steroidogenic factor 1 (SF-1), and early growth response protein 1 (egr-1)
      binding sites form a tripartite gonadotropin-releasing hormone response element
      in the rat luteinizing hormone-beta gene promoter: an integral role for SF-1.
AB  - Recently, several cis-regulatory elements that play roles in LHbeta gene
      expression, and their cognate DNA-binding transcription factors, have been
      identified. These factors include Sp1, steroidogenic factor-1 (SF-1), and early
      growth response protein 1 (Egr-1). Using the GH3 pituitary cell line (which lacks
      SF-1) as a model, we demonstrate that expression of SF-1 or Egr-1 increases rat
      LHbeta gene promoter activity but has little effect on the fold response to GnRH.
      However, expression of both SF-1 and Egr-1 synergistically enhances LHbeta gene
      promoter activity and prevents further stimulation of activity by GnRH. Mutations
      in the Sp1 binding sites of the rat LHbeta gene promoter decrease GnRH
      responsiveness, whereas mutations in the SF-1 and/or Egr-1 binding sites alone
      have little effect on the GnRH response. Combinatorial mutations in both the Sp1
      and Egr-1 binding elements result in almost complete loss of the GnRH response.
      In contrast, in GH3 cells cotransfected with SF-1, mutations in the Sp1, SF-1, or
      Egr-1 binding elements independently decrease GnRH responsiveness. In LbetaT2
      cells, a gonadotrope-derived cell line that expresses SF-1 endogenously,
      mutations in either the Sp1 or Egr-1 binding elements decrease GnRH
      responsiveness. These data suggest that the Sp1, SF-1, and Egr-1 binding sites
      form a tripartite GnRH response element in the rat LHbeta gene promoter. Changes
      in the spacing between the upstream Sp1 binding sites and the downstream SF-1/Egr
      1 binding elements reduce the response to GnRH. SF-1, while having little direct
      effect on GnRH responsiveness, has a critical role in integrating the effects of
      Sp1 and Egr-1.

PMID- 10935548
TI  - The Otx2 homeoprotein regulates expression from the gonadotropin-releasing
      hormone proximal promoter.
AB  - The GnRH gene is expressed exclusively in a highly restricted population of
      approximately 800 neurons in the mediobasal hypothalamus in the mouse. The Otx2
      homeoprotein has been shown to colocalize with GnRH in embryonic mouse brain. We
      have identified a highly conserved bicoid-related Otx target sequence within the
      proximal promoter region of the GnRH gene from several species. This element from
      the rat GnRH promoter binds baculovirus-expressed Otx2 protein and Otx2 protein
      in nuclear extracts of a hypothalamic GnRH-expressing neuronal cell line, GT1-7.
      Transient transfection assays indicate that the GnRH promoter Otx/bicoid site is
      required for specific expression of the GnRH gene in GT1-7 cells and that it can
      confer specificity to a neutral Rous sarcoma virus (RSV) promoter in GT1-7 cells
      but not in NIH3T3 cells. Overexpression of mouse Otx2 in GT1-7 cells induces
      expression of a GnRH promoter plasmid, an effect that is dependent upon the Otx
      binding site. Thus, the GnRH proximal promoter is regulated by the Otx2
      homeoprotein. Finally, we have now demonstrated the presence of Otx2 protein in
      the GnRH neurons of the adult mouse hypothalamus. These data suggest that Otx2 is
      important in the development of the GnRH neuron and/or in the maintenance of GnRH
      expression in the adult mouse hypothalamus.

PMID- 10935549
TI  - The three subfamilies of leucine-rich repeat-containing G protein-coupled
      receptors (LGR): identification of LGR6 and LGR7 and the signaling mechanism for
      LGR7.
AB  - Glycoprotein hormone receptors, including LH receptor, FSH receptor, and TSH
      receptor, belong to the large G protein-coupled receptor (GPCR) superfamily but
      are unique in having a large ectodomain important for ligand binding. In addition
      to two recently isolated mammalian LGRs (leucine-rich repeat-containing, G
      protein-coupled receptors), LGR4 and LGR5, we further identified two new
      paralogs, LGR6 and LGR7, for glycoprotein hormone receptors. Phylogenetic
      analysis showed that there are three LGR subgroups: the known glycoprotein
      hormone receptors; LGR4 to 6; and a third subgroup represented by LGR7. LGR6 has
      a subgroup-specific hinge region after leucine-rich repeats whereas LGR7, like
      snail LGR, contains a low density lipoprotein (LDL) receptor cysteine-rich motif
      at the N terminus. Similar to LGR4 and LGR5, LGR6 and LGR7 mRNAs are expressed in
      multiple tissues. Although the putative ligands for LGR6 and LGR7 are unknown,
      studies on single amino acid mutants of LGR7, with a design based on known LH and
      TSH receptor gain-of-function mutations, indicated that the action of LGR7 is
      likely mediated by the protein kinase A but not the phospholipase C pathway.
      Thus, mutagenesis of conserved residues to allow constitutive receptor activation
      is a novel approach for the characterization of signaling pathways of selective
      orphan GPCRs. The present study also defines the existence of three subclasses of
      leucine-rich repeat-containing, G protein-coupled receptors in the human genome
      and allows future studies on the physiological importance of this expanding
      subgroup of GPCR.

PMID- 10935550
TI  - Constitutive activation of G protein-coupled receptors as a result of selective
      substitution of a conserved leucine residue in transmembrane helix III.
AB  - Whereas numerous mutations of the human lutropin receptor (hLHR) and human TSH
      receptor (hTSHR) have been shown to cause constitutive activation of these
      receptors, it has been suggested that either the hFSHR as a whole, or the i3/TM
      VI region of the hFSHR, is less susceptible to mutation-induced constitutive
      activation. However, as shown herein, substitution of a highly conserved leucine
      residue in transmembrane III (TM III) of the hFSHR (Leu 111.18) with arginine
      causes a 5-fold increase in basal cAMP in transfected cells, consistent with a
      strong constitutive activation of the hFSHR. Interestingly, this mutant is
      unresponsive to further hormonal stimulation. Substitutions of hFSHR(L460) with
      lysine, alanine, or aspartate show that only arginine causes constitutive
      activation. However, all result in decreased FSH responsiveness, suggesting a
      role for L460 in FSH-stimulated cAMP production by the hFSHR. Because Leu 111.18
      is highly conserved in rhodopsin-like G protein-coupled receptors (GPCRs), we
      tested the effects of substitution of the comparable leucine in the human beta2
      adrenergic receptor (hbeta2-AR). Substitution of L124 in the hbeta2-AR with
      arginine, lysine, or alanine resulted in constitutive activation as evidenced by
      increased basal levels of cAMP that could be attenuated by an inverse agonist. In
      all cases, isoproterenol-stimulated cAMP was unaffected. Taken altogether, our
      data support a model whereby Leu 111.18 may play a general role in GPCRs by
      stabilizing them in an inactive state. Constitutive activation may arise by both
      a disruption of Leu 111.18 as well as the introduction of a specific residue that
      serves to stabilize the active state of the receptor.

PMID- 10935552
TI  - History of mechanical circulatory support.
AB  - End-stage heart failure exerts a tremendous impact on individuals and society in
      terms of personal and economic suffering. The development of mechanical
      circulatory support devices has been driven by the shortage of donor organs for
      heart transplantation. Collaborative efforts in the fields of surgery, medicine,
      and biomedical engineering, sponsored by both government and industry, have led
      to devices capable of providing reliable circulatory support. Future mechanical
      cardiac assist devices will likely play an important role in the treatment of an
      ever-growing population of patients with end-stage heart failure.

PMID- 10935551
TI  - Follicle-Stimulating hormone (FSH) stimulates phosphorylation and activation of
      protein kinase B (PKB/Akt) and serum and glucocorticoid-lnduced kinase (Sgk):
      evidence for A kinase-independent signaling by FSH in granulosa cells.
AB  - FSH stimulates in ovarian granulosa cells diverse, differentiation-dependent
      responses that implicate activation of specific cellular signaling cascades. In
      these studies three kinases were investigated to determine their relationship to
      FSH, cAMP, and A kinase signaling: protein kinase B (PKB/Akt), serum and
      glucocorticoid-induced kinase (Sgk), and p38 mitogen-activated protein kinase
      (p38MAPK). The phosphorylation (activation) of these kinases was analyzed by
      using selective agonists/inhibitors: forskolin/H89 for cAMP-dependent protein
      kinase (A kinase), insulin-like growth factor I (IGF-I)/LY294002 and wortmannin
      for phosphatidylinositol-dependent kinase (PI3-K), and phorbol myristate
      (PMA)/GF109203X for diacylglycerol and Ca++-dependent kinases (C kinases). An
      inhibitor (PD98059) of MEK1, which regulates extracellular regulated kinases
      (ERKs), and SB203580, which inhibits p38MAPK, were also used. In addition, we
      analyzed the expression of the recently described, cAMP-regulated guanine
      nucleotide exchange factors (cAMP-GEFI and GEFII) that impact Ras-related GTPases
      and Raf kinases, known regulators of various protein kinase cascades. We provide
      evidence that FSH, forskolin, and 8-bromo-cAMP stimulate phosphorylation of PKB
      by mechanisms involving PI3-K (LY294002/wortmannin sensitive) not A kinase (H89
      insensitive), a pattern of response mimicking that of IGF-I. In contrast, FSH
      induction and phosphorylation of Sgk protein requires A kinase (H89 sensitive)
      but also involves PI3-K (LY294002 sensitive) as well as p38MAPK (SB203580
      sensitive) pathways. PMA (C kinase) abolished FSH-mediated (but not IGF-I
      mediated) phosphorylation of PKB at a step(s) upstream of PI3-K and independent
      of A kinase. Lastly, FSH-mediated phosphorylation of p38MAPK is negatively
      affected by A kinase and PI3-K, suggesting that it may be downstream of specific
      members of the cAMP-GEF/Rap/Raf pathway. We propose that cAMP activation of A
      kinase is obligatory for transcription of Sgk in granulosa cells whereas cAMP
      (IGF-I-like)-mediated phosphorylation (activation) of PKB and Sgk (via PI3-K), as
      well as p38MAPK, involves other cellular events. These results provide new and
      exciting evidence that cAMP acts in granulosa cells by A kinase-dependent and 
      independent mechanisms, each of which controls specific kinase cascades.

PMID- 10935553
TI  - Left ventricular assist device as a bridge to patient and myocardial recovery.
AB  - This article reviews the effects of chronic left ventricular assist device
      implantation on functional changes in patients with end-stage heart disease.
      Functional recovery can be measured by using response to exercise, quality-of
      life surveys, improvements in noncardiac organ function, or changes in metabolic
      and neurohormonal levels. Recovery in intrinsic function of the heart can be
      assessed by changes in cardiac pump function or in baseline histological or
      biochemical abnormalities. Improvements in all of these areas have been found,
      although many reported studies are limited by a small sample size from selected
      subsets of patients rather than consecutive series.

PMID- 10935554
TI  - Left ventricular assist device-induced reverse ventricular remodeling.
AB  - Left ventricular assist devices provide chronic pressure and volume unloading of
      the dilated left ventricle in patients with end-stage heart failure. This is
      associated with reverse structural remodeling (normalization of the passive
      pressure-volume relationship), reverse molecular remodeling (increased expression
      of several genes involved in calcium metabolism that are down-regulated in heart
      failure), improved baseline contractility, and improved contractile response to
      increased heart rate and to beta-agonist stimulation. These findings indicate the
      profound degree of recovery of myocardial properties in hearts previously
      considered to have invincible end-stage heart failure.

PMID- 10935555
TI  - Clinically available extracorporeal assist devices.
AB  - Mechanical circulatory support has been shown to be of benefit to allow recovery
      after conventional heart surgery and as a successful bridge to heart
      transplantation. Recent clinical trials with implantable left ventricular assist
      devices (LVADs) have been completed with these devices showing restoration of
      normal hemodynamics and successful bridge to transplantation. A major advantage
      of the implantable devices is the ability for the patient to be discharged and
      followed up at an outpatient setting. However, multiple advantages to
      extracorporeal devices still remain, which are the focus of this review. One
      advantage of the extracorporeal devices is that they can be placed in much
      smaller patients than currently available implantable LVADs. Also, because of
      differences in design of the assist devices, the extracorporeal devices can be
      placed without the need for the cardiopulmonary bypass and with decreased
      operative time and dissection. Perhaps the biggest advantage of the
      extracorporeal devices is that they can provide a support for both the right and
      left side of the heart as opposed to the implantable LVADs, which are only used
      as left ventricular assist devices. This article describes in detail the
      advantages and disadvantages of the extracorporeal devices as well as the
      operative techniques used to implant them. As the number of patients with heart
      failure continues to rise, so will the need for mechanical circulatory support.
      Though the majority of these patients will be served by a long-term implantable
      device, there will remain a subset of patients that will be best suited for
      treatment with extracorporeal devices.

PMID- 10935556
TI  - Clinically available intracorporeal left ventricular assist devices.
AB  - There are now 3 commercially approved intracorporeal left ventricular assist
      devices (LVADs). Product similarities include (1) LV apex, to pump, to ascending
      aorta flow patterns, (2) excellent hemodynamic support with reversal of heart
      failure and neurohormone/cytokine milieu, and (3) the requirement of major
      surgery for device implantation and later explantation, with or without
      transplant. Two electrically powered models allow a tether-free existence and
      hospital discharge. All complications are being addressed, and in the past
      decade, device failure and thromboemboli have been reduced. Infection continues
      to be an obstacle to more widespread adoption of therapy. Despite pre-LVAD shock,
      most patients (65% to 78% by Food and Drug Administration data) survive until
      transplant (averaging 80 to 96 days of LVAD support), and posttransplant survival
      is equal to nonbridged patients. As the problem of infection is reduced, more
      widespread LVAD use can be anticipated.

PMID- 10935557
TI  - Perioperative management of the left ventricular assist device recipient.
AB  - An understanding of the unique preoperative, intraoperative, and postoperative
      considerations of left ventricular assist device implantation is essential for
      the successful anesthetic management of these challenging cases. This article
      discusses the different stages of anesthetic care of the left ventricular assist
      device recipient, including preoperative assessment, lining, induction,
      separation from cardiopulmonary bypass, and the postbypass period.

PMID- 10935558
TI  - Outpatient left ventricular assist device support: a safe and economical
      therapeutic option for heart failure.
AB  - The left ventricular assist device (LVAD), once considered for acute cardiac
      failure only when no other therapeutic option was available, is now used
      routinely at selected centers to allow the sickest patients to become self
      sufficient and go home. This represents a dramatic change in the physician's
      perception of the LVAD in the early 1990s. The creation of these mechanical
      assist outpatient programs are possible for the following reasons: 1) confidence
      in the devices allow patients, their families, and health care providers to be
      more comfortable with outpatient therapy; 2) the devices are simplified and
      durable, allowing extended duration of support and more options for patients; and
      3) a change in the perception of the LVAD from a last-resort therapeutic option
      to that of a safe and reliable bridge to recovery and transplant. With these
      general concepts in mind, programs have been created with specific safety nets,
      patient education goals, and discharge criteria. By using this construct, we have
      developed a successful outpatient LVAD program in which 70% of our vented
      electric LVAD patients were discharged with a 0% mortality and minimal morbidity.
      From our experience and studies, we believe that not only is an outpatient LVAD
      program safe and economical, but it is also socially, physically, and
      psychologically beneficial to the patient. In the current economic environment of
      cost containment, outpatient LVAD therapy is a necessary part of an LVAD program
      that should be sought by most cardiac mechanical assist programs.

PMID- 10935559
TI  - Immunobiology of left ventricular assist devices.
AB  - The increasing use of implanted biomaterial devices has made it evident that no
      material is biologically inert. As a result of direct contact with elements of
      the blood circulation, such as during hemodialysis or after left ventricular
      assist device (LVAD) implantation, significant changes in systemic immunologic
      and thrombostatic functions occur. The clinical success of LVAD implantation has,
      nevertheless, been accompanied by complications arising from an aberrant state of
      monocyte and T-cell activation, leading to heightened susceptibility of
      circulating CD4 T cells to undergo activation-induced cell death; this results in
      progressive defects in cellular immunity and an increased risk of serious
      infection. Because of the increased state of T-cell activation and the selective
      loss of Th1 cytokine producing CD4 T cells, LVAD recipients also develop B-cell
      hyperreactivity and dysregulated immunoglobulin syntheses by unopposed production
      of Th2 cytokines and increased CD40 Ligand-CD40 interactions. LVADs are currently
      being evaluated as a permanent therapy for end-stage heart failure. Because these
      immune dysfunctions appear to be related to the effects of excessive biomaterial
      associated T-cell activation, future efforts will need to be directed at either
      altering the physical properties of the materials interacting with the host
      circulation or pharmacological intervention aimed at inhibiting T-cell
      activation.

PMID- 10935560
TI  - Economic impact of mechanical cardiac assistance.
AB  - In contrast to heart transplantation, little effort has been made to estimate the
      economic implications of mechanical cardiac assistance from either a procedure-
      or a program-level perspective. With annual direct and indirect expenditures for
      the treatment of coronary artery disease and congestive heart failure now
      exceeding $65 billion in the United States, and the treatment options available
      for these diseases becoming increasingly diverse, it is important that we begin
      to better understand how expenditures for various treatment options compare. From
      a disease management perspective, it is also essential that policymakers have
      credible estimates of total program expenditures. At this time, program
      expenditures for heart transplantation in the United States are somewhere between
      $352 and $700 million. Given the availability of viable long-term mechanical
      cardiac assistance and the current need for cardiac replacement, total direct
      annual program expenditures could be as low as $5.4 billion or as high as $24
      billion, depending on the expenses associated with device implantation and
      maintenance. By contrast, in 1996 the United States spent $9.8 billion on the
      treatment of end-stage renal disease. Clearly, the economics are such that viable
      mechanical cardiac assistance will likely engender considerable public policy
      debate.

PMID- 10935561
TI  - Future devices and directions.
AB  - This article summarizes the status of left ventricular assist devices currently
      in the stages of bench testing, animal experiments, and pilot clinical trials.
      The major design features and estimate of costs for 17 devices are described
      under 3 major categories of indications for use: destination therapy, bridge to
      transplant, and bridge to recovery. A sleeved piston pump located in the aorta
      and a unique, magnetically suspended centrifugal pump are described in the
      destination therapy section. Eight centrifugal and 4 axial flow devices are
      listed in the bridge to transplant category, and an external cup and a very low
      cost centrifugal pump with a left atrium-to-aorta circuit are described in the
      bridge to recovery section. The key design features of the future, which will be
      required for success in both the clinical and marketplace arenas, will be
      simplicity, safety, low-power requirements, and low cost.

PMID- 10935562
TI  - Changes in methods of male youth suicide: 1980-95.
AB  - AIMS: To determine if there have been changes in the methods used, particularly
      hangings, for male youth suicides; whether any changes were similar to those for
      other age groups; and to what degree any changes identified may have impacted on
      overall suicide rates. METHOD: All males aged fifteen to 24 years of age who died
      between 1980 and 1995 inclusive, and whose death was assigned one of the WHO
      external cause codes for "suicide and self-inflicted injury" (E950-E959), were
      selected from the New Zealand Health Information Services national mortality
      database. RESULTS: The rate for suicide by hanging was relatively low and stable
      in the early 1980's. By 1985 it had started to increase dramatically up until
      1989, at which point it become stable again. The substantive increase in hangings
      was largely confined to males aged 24 years and younger. The increase in suicide
      by hanging cannot be attributed to substitution in methods as the rates for all
      other methods have also increased, albeit less dramatically. CONCLUSIONS: Much of
      the increase in suicide among male youths is due to an increase in hanging. The
      reasons for the choice of this method are unknown, and warrant study.

PMID- 10935563
TI  - Initial experience with the freestyle stentless aortic bioprosthesis.
AB  - AIMS: We report our initial experience with the Freestyle aortic bioprosthesis.
      METHODS: This prosthesis was implanted in 40 patients between February 1993 and
      December 1998. Operative indications were aortic stenosis in 32 patients (80%),
      aortic regurgitation in seven patients (18%) and a combined lesion in one (3%).
      The mean patient age was 71.4+/-9.7 (SD) years, with 29 (72%) females. Pre
      operative New York Heart Association (NYHA) class was III or IV in 28 (70%). Left
      ventricular systolic function was impaired in four (10%). Six (15%) patients had
      undergone previous cardiac surgery. Concomitant procedures were carried out in 21
      patients (53%). RESULTS: Early mortality was zero. Early morbidity included three
      re-operations for bleeding, one cerebrovascular event, one haemorrhagic
      complication and one case of valve dysfunction. At follow up (range 4.6 to 75.6
      months, mean 29.5+/-25.5) there has been one (3%) late death which was non valve
      related, one (3%) episode of study-valve endocarditis, and three (8%)
      thromboembolic episodes. NYHA Class was I or II in all but one survivor.
      Echocardiographic follow-up has shown no further instances of valve dysfunction
      with satisfactory haemodynamic parameters at 24-months post-operation, and a
      significant and sustained regression of left ventricular mass. CONCLUSIONS: The
      initial experience with the Freestyle valve is that it results in good clinical
      and haemodynamic performance, suggesting it as an ideal bioprosthesis for this
      patient group.

PMID- 10935564
TI  - Job satisfaction, psychological morbidity and job stress among New Zealand
      general practitioners.
AB  - AIM: To assess levels of psychological distress and job satisfaction among New
      Zealand general practitioners. METHODS: A random sample of general practitioners
      (GPs) in the central region of the North Island were surveyed using a postal
      questionnaire. Job satisfaction and psychological distress (twelve-item General
      Health Questionnaire, GHQ-12) were assessed and compared with personal, practice
      and workload characteristics. Qualitative statements about work conditions
      sources of stress and ill health were also collected. RESULTS: The response rate
      was 391/480 (81.5%). Job satisfaction scores were generally high. Rural GPs were
      less satisfied than urban practitioners and solo practitioners less satisfied
      than those in group practice. Work was perceived as affecting the physical health
      of 177 GPs (46%) and 220 (57%) often contemplated leaving general practice. 121
      GPs (31.4%) scored >3 on the GHQ-12 showing high levels of psychological symptoms
      and 39 (9.9%) scored greater than eight, indicating significant psychological
      distress. Major causes of stress and lack of job satisfaction were: excessive
      paperwork, health reforms and bureaucratic interference, excessive hours and on
      call work. CONCLUSIONS: Overall, GPs were satisfied with their jobs. Levels of
      psychological symptoms were of concern, particularly in the 10% showing very high
      levels of psychological distress, and in rural and solo practitioners.

PMID- 10935565
TI  - Stereotactic breast biopsies for lesions discovered on routine mammography:
      experience at the North Shore Hospital.
AB  - AIM: To review the efficacy of stereotactic breast biopsies performed at the
      North Shore Hospital. METHOD: Out of 118 consecutive biopsies carried out between
      1992 and 1998, performed on impalpable lesions found on routine mammography, 102
      with adequate follow-up data were reviewed, with particular regard to the
      sensitivity and accuracy of the technique in the diagnosis of breast cancer. The
      techniques and equipment employed are described. RESULTS: The results were
      comparable to those described in the literature, with a sensitivity of 88.9%,
      specificity of 97.6% and overall accuracy of 97.1%. The procedure was found to be
      well-tolerated by patients. CONCLUSIONS: The method was found to be accurate,
      safe and inexpensive.

PMID- 10935566
TI  - Nutritional supplement use among 26-year-olds.
AB  - AIMS: To estimate the prevalence of use of nutritional supplements among young
      adults, to examine the source of those supplements and to investigate sex
      differences in usage. METHODS: Participants in the age-26 years assessments of
      the Dunedin Multidisciplinary Health and Development Study were asked to bring
      containers for any medication (including supplements) taken in the previous two
      weeks. Medication data (including prescription source) were recorded and analysed
      for 978 of 980 Study members. RESULTS: The prevalence of supplement use was
      16.6%; 20.4% among females and 13.3% for males (p<0.01). Multivitamin
      preparations were the most widely consumed, followed by water-soluble vitamin
      supplements (such as folate and vitamin C). Folate use was higher among females
      and was taken by 35.7% of pregnant females. Most supplements were self
      prescribed, although a doctor had prescribed over one-third of the mineral
      supplements. Most supplements had been taken for weeks or months, rather than
      years. CONCLUSIONS: Nutritional supplement usage among young adults is reasonably
      common, and involves a wide range of preparations. The extent of use among
      younger people suggests a need for regulation of their manufacture, sale and
      usage, and research to examine their efficacy.

PMID- 10935567
TI  - Estimated number of cases of foodborne infectious disease in New Zealand.
AB  - AIMS: To estimate the annual number of cases of infectious intestinal disease
      caused by foodborne pathogens in New Zealand and estimate the impact of these
      diseases in terms of days lost to illness. METHODS: Incidence of foodborne
      diseases were derived from data from infectious disease surveillance and hospital
      sources, and estimates of unreported illnesses using published population based
      studies. RESULTS: The estimated number of cases of foodborne infectious disease
      is approximately 119 000 per year, including 19 000 general practitioner visits,
      400 hospital admissions, 22 cases of long term illness and two deaths. It is
      estimated that the number of cases of potentially foodborne infectious disease is
      approximately 199 000. Total number of cases of all infectious intestinal disease
      could be as high as 823 000. Days of lost production and leisure time activities
      lost to foodborne infectious disease are estimated as approximately 497 000.
      CONCLUSION: Foodborne infectious diseases represent a major public health burden
      in terms of the number of cases and days lost to illness.

PMID- 10935568
TI  - Economic cost to New Zealand of foodborne infectious disease.
AB  - AIMS: To estimate the annual economic cost to New Zealand of foodborne infectious
      disease. METHODS: Annual incidence rates were combined with unit cost data to
      derive estimates of the annual economic cost to society of each foodborne
      infectious disease. Market prices and wages were used as proxies for the unit
      costs of resource utilisations. A decision analytic model was developed to
      estimate the costs of each disease and to undertake sensitivity analysis.
      RESULTS: There are an estimated 119 320 episodes of foodborne infectious disease
      per year in New Zealand (3241 per 100 000 population). The total cost of these
      cases was $55.1 million ($462 per case) made up of direct medical costs of $2.1
      million, direct non-medical costs of $0.2 million, indirect cost of lost
      productivity of $48.1 million, and intangible cost of loss of life of $4.7
      million. Campylobacteriosis generated most of the costs. Lost productivity was
      the major cost component for all diseases. The total cost of potentially
      foodborne infectious disease was estimated to be $88.8 million. Broad estimates
      of additional costs due to cases of infectious intestinal diseases caused by non
      foodborne pathogens or for which no pathogen is identified could raise the cost
      to $215.7 million. CONCLUSION: The findings imply that resources of $55 million
      could be devoted to prevention of foodborne infectious disease. Efforts should
      focus on lowering the incidence of campylobacteriosis as this disease accounts
      for most of foodborne illness costs.

PMID- 10935570
TI  - "Just say no"--reducing the use of antibiotics for colds, bronchitis and
      sinusitis.

PMID- 10935569
TI  - Acute otitis media: antimicrobial therapy in an era of resistant bacteria and
      sceptical meta-analysticians.

PMID- 10935571
TI  - Prevention of infective endocarditis associated with dental treatment and other
      medical interventions.

PMID- 10935572
TI  - Freedom of open, scientific debate and legal threats.

PMID- 10935573
TI  - Advertising bans and cigars.

PMID- 10935575
TI  - Freedom of debate and legal threats.

PMID- 10935574
TI  - When do parents have the right to refuse medical treatment on behalf of their
      children?

PMID- 10935576
TI  - Medical training.

PMID- 10935578
TI  - Professional misconduct.

PMID- 10935577
TI  - A Boston tea party.

PMID- 10935579
TI  - Second thoughts about second opinions.

PMID- 10935580
TI  - The effect of hypotensive anesthesia on blood loss and operative time during Le
      Fort I osteotomies.
AB  - PURPOSE: The purpose of this prospective study was to compare the quality of the
      surgical field, blood loss, and operative time with either hypotensive or
      normotensive anesthesia during Le Fort I osteotomies. PATIENTS AND METHODS:
      Twenty-three patients were randomized into normotensive or hypotensive anesthesia
      treatment groups. The quality of the surgical field was assessed intraoperatively
      by direct observation and again postoperatively using video imaging. A
      standardized rating scale was applied at specific intervals by surgeons blinded
      to the anesthetic technique. The surgical time was measured on the videotape, and
      blood loss was measured by volumetric and gravimetric techniques. RESULTS: There
      was a statistically significant correlation (P < .0001) between the surgeon's
      perception of the quality of the surgical field and the blood pressure. There was
      also a statistically significant reduction (P < .01) in blood loss when using
      hypotensive anesthesia. However, there was no statistically significant reduction
      (P = .44) in operative time when using hypotensive anesthesia. CONCLUSIONS: It
      was concluded that hypotensive anesthesia is valuable in reducing blood loss and
      improving the quality of the surgical field during Le Fort I osteotomies,
      allowing for easier, more deliberate, and careful dissection. However, it does
      not reduce operative time.

PMID- 10935581
TI  - Neurosensory recovery after ligation of the descending palatine neurovascular
      bundle during Le Fort I osteotomy.
AB  - PURPOSE: The effect of ligating the descending palatine neurovascular bundle
      (DPNB) on the recovery of palatal sensation has not been clearly established. The
      purpose of this study was to determine the effect of ligation of the DPNB on the
      recovery of palatal sensation after Le Fort I osteotomy. PATIENTS AND METHODS:
      Using a retrospective study design in a randomized protocol, patients who had
      undergone Le Fort I osteotomy were assigned to either treatment group 1 (DPNB
      ligated) or treatment group 2 (DPNB preserved). A third group of control patients
      (group 3, unoperated) on whom no surgery had been performed served as a baseline
      for examination of normal palatal sensation. The predictor variables were
      ligation and preservation of the DPNB. The outcome variables were mean tactile
      sensation and mean nociception. Other study variables included age, sex, follow
      up, surgical movements, and number of segments. RESULTS: There were 11 patients
      in group 1, 7 in group 2, and 10 in group 3. For tactile sensation, the mean Von
      Frey hair size detected was 4.26 +/- 0.37, 4.11 +/- 0.17, and 3.68 +/- 0.24 for
      groups 1, 2, and 3, respectively. The difference between group 1 and group 2 was
      not significant (P > .05). The differences between group 1 and group 3 and
      between group 2 and group 3 were significant (P < .05). For nociception, the mean
      pressure was 51.09 +/- 21.73, 50.89 +/- 19.19, and 56.25 +/- 19.02 for groups 1,
      2, and 3, respectively. The difference between the 3 groups was not significant
      (P = .8064). CONCLUSION: The results of this study suggest that recovery of
      palatal sensation is not adversely affected by ligation of the DPNB.

PMID- 10935583
TI  - Long-term evaluation of arthrocentesis for the treatment of internal derangements
      of the temporomandibular joint.
AB  - PURPOSE: Arthrocentesis is being used for treatment of patients with
      temporomandibular joint disorders, including anterior disc displacement with and
      without reduction. This study was designed to examine the long-term effects of
      temporomandibular joint arthrocentesis in such patients and to evaluate their
      overall satisfaction with this treatment. PATIENTS AND METHODS: The study was
      based on the review of patients' records, a written questionnaire (self
      evaluation), and clinical examination. Visual analog scales (VAS) were used for
      evaluation of pain and dysfunction. Twenty-six patients (39 joints) who had been
      treated at the Medical College of Virginia Hospital, Virginia Commonwealth
      University, were included in the study. There were 32 joints with anterior disc
      displacement without reduction (ADsR) and 7 joints with anterior displacement
      with reduction (ADcR). Patients all had undergone arthrocentesis as outpatients.
      Follow-up evaluations ranged from 10 to 96 months, with a mean of 48.7 months.
      RESULTS: Maximum vertical opening (MVO) prearthrocentesis ranged from 20 to 40
      mm, with a mean of 25.3 +/- 5.5 mm. Immediately after arthrocentesis, the MVO
      ranged from 30 to 55 mm, with a mean of 43.8 +/- 5.6 mm. Maximum vertical opening
      at long-term follow-up ranged from 15 to 50 mm, with a mean of 37.1 +/- 8.8 mm.
      There was a significant increase in MVO between prearthrocentesis and
      postarthrocentesis both short- and long-term (P < .001). The short- and long-term
      postoperative VAS values for pain and dysfunction showed a significant decrease
      (P < .001) when compared with the VAS values preoperatively. Fourteen of the 26
      patients (54%) no longer experienced pain, and the remaining 9 had less pain than
      before arthrocentesis as assessed by self-evaluation and clinical examination.
      Three of 26 patients had improvement for a period, later relapsed, and required
      subsequent surgery. Twenty-three of the 26 patients (88%) were completely
      satisfied with their treatment. Overall, an 88% success rate was achieved.
      CONCLUSION: Arthrocentesis can reduce pain and dysfunction, both short- and long
      term, in patients with anterior disc displacement.

PMID- 10935582
TI  - Endonasal endoscopic reduction of blowout fractures of the medial orbital wall.
AB  - PURPOSE: This article describes the endonasal endoscopic reduction (EER) of
      blowout fractures (BOFs) of the medial orbital walls and reports the clinical
      results. PATIENTS AND METHODS: Sixteen patients who underwent EER for a BOF of
      the medial orbital wall were analyzed. The surgical indications for treatment
      were diplopia, limitation of eye movements, and significant enophthalmos. They
      were followed-up for at least 3 months after the surgery. Surgical techniques,
      surgical results, and postoperative complications were reviewed. RESULTS: There
      were no significant intraoperative or postoperative complications. Fourteen
      patients showed complete resolution of symptoms after the surgery. One patient,
      who had persistent diplopia and remaining enophthalmos, underwent medial wall
      reconstruction with a Medpor surgical implant (Porex Surgical Inc, College Park,
      GA) by a transorbital approach. Another patient, who had residual enophthalmos,
      had correction of enophthalmos after insertion of a Medpor implant. Both patients
      are now symptom-free. CONCLUSION: The results indicate that EER is a safe and
      effective technique for the treatment of BOFs of the medial orbital wall.

PMID- 10935584
TI  - Late mandibular fracture after third molar surgery: a survey of Connecticut oral
      and maxillofacial surgeons.
AB  - PURPOSE: This study investigated the incidence and causative factors involved in
      late mandibular fractures after third molar surgery. MATERIALS AND METHODS: A
      questionnaire was sent to 106 oral and maxillofacial surgeons in Connecticut,
      asking them about their experience with late fractures over a 10-year period.
      RESULTS: A 79% response indicated 28 fractures occurring in 611,000 extractions,
      for an incidence of 0.0046%. The cause was found to be multifactorial and
      included age, gender, type of impaction, preexisting infection, and failure to
      maintain a soft diet in the postoperative period. Most fractures occurred between
      the 1st and 21st days postoperatively. Three of the fractures resulted in
      malpractice litigation. CONCLUSION: Men over the age of 25 years should be
      specifically informed about the risk of late mandible fracture after third molar
      surgery. This group of patients should be educated about the quality and duration
      of a soft diet.

PMID- 10935585
TI  - Cytokeratin expression in the odontogenic keratocyst.
AB  - PURPOSE: This study attempted to identify differential cytokeratin expression in
      cystic jaw lesions using immunohistochemical staining. PATIENTS AND METHODS: The
      charts from selected patients treated between 1983 and 1994 for jaw cysts were
      evaluated. Twenty-four paraffinized specimens were selected randomly for
      investigation with 5 immunohistochemical stains. The 4 diagnostic categories
      included ameloblastoma, dentigerous cyst, odontogenic keratocyst (OKC), and
      recurrent odontogenic keratocyst in patients with nevoid basal cell carcinoma
      (NBCC) syndrome. The 5 immunohistochemical stains included antibodies to
      cytokeratins 13, 17, and 18; CAM 5.2; AE 1/3; and carcinoembryonic antigen (CEA).
      RESULTS: Differential staining of OKCs from patients with and without NBCC
      syndrome was found only with the antibody to cytokeratin 17. Furthermore,
      staining of OKCs in syndromic patients appeared to be stronger and more uniform
      than in nonsyndromic patients. CONCLUSIONS: These findings suggest that
      immunohistochemical staining for cytokeratin 17 may aid in the diagnosis of OKCs
      and may be used to further subdivide these lesions based on the presence or
      absence of NBCC syndrome.

PMID- 10935586
TI  - Macroscopic and microscopic details of the cartilaginous nasal pyramid.
AB  - PURPOSE: The purpose of this investigation was to ascertain the macroscopic and
      microscopic details at rhinion and throughout the cartilaginous nasal pyramid in
      35 white cadavers. MATERIALS AND METHODS: Demographic information on 35 white
      cadavers was collected. This included sex, height, weight, brief medical history,
      age at death, and cause of death. All soft tissues were removed from the nasal
      bones, lateral nasal cartilages, and alar cartilages and the overlap between bone
      and cartilage was measured at 4 sites. The lateral nasal cartilage (LNC) was
      measured for width and length. The relationship between the caudal end of the
      LNC, and the anterior septal angle was also noted. The septum and LNC were
      removed en bloc randomly from 25 of the cadavers. These specimens were fixed in
      formalin, processed, embedded in paraffin, and coronally sectioned every 3 mm,
      and prepared for microscopic examination. RESULTS: The LNC was 22.51 mm long and
      13.71 mm wide on average. It underlapped the nasal bone 14.97 mm on average from
      the nasal septum laterally. The cephalocaudal underlapping was greatest in the
      midline (mean, 8.63 mm) and least (2.77 mm) about halfway down the nasal bone.
      Microscopic examination showed extreme variation in the attachment of the septum
      and LNC. This ranged from no cartilaginous connection to complete fusion. Thirty
      two percent of the specimens showed the caudal edge of the LNC to be coincident
      with the anterior septal angle. CONCLUSIONS: At the time of aesthetic,
      functional, or post-traumatic nasal surgery, one must be prepared to deal with
      diverse attachments between the septum and the LNC.

PMID- 10935588
TI  - Rapidly enlarging lesion of the upper lip.

PMID- 10935587
TI  - Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated
      implants in the tibia of mature rats.
AB  - PURPOSE: The purpose of this study was to examine the effects of estrogen
      deficiency on bone remodeling adjacent to implants in the tibia of mature rats.
      MATERIALS AND METHODS: Hydroxyapatite-coated implants were placed bilaterally in
      the proximal metaphysis of the tibia of 18 female Wistar rats (48 weeks old), and
      ovariectomy was performed 168 days later. As a control, sham ovariectomy was
      performed in a similar group of 18 rats. Six animals from each group were killed
      at 28, 84, and 168 days after ovariectomy. Undecalcified sections were prepared,
      and changes in the bone tissue around the implants were evaluated histologically.
      Histomorphometric measurements were made with a computer-based image analyzer to
      quantify the unit bone mass around each implant and the amount of implant-bone
      contact. RESULTS: In the cortical bone area, ovariectomy induced only a slight
      decrease in bone contact with the implant, compared with that in the sham
      operated rats. However, both the bone volume around the implant and implant-bone
      contact were significantly decreased in the cancellous bone area in
      ovariectomized rats compared with the sham-operated rats. CONCLUSION: Thinning of
      the bone trabeculae holding dental implants may occur with estrogen deficiency.

PMID- 10935589
TI  - Isolation of particulate degradation debris 1 year after implantation of a Guidor
      membrane for guided bone regeneration: case report.

PMID- 10935590
TI  - Oncocytoma of an intraoral minor salivary gland: report of a case and review of
      literature.

PMID- 10935591
TI  - Internal jugular vein phlebectasia: case report.

PMID- 10935592
TI  - Squamous cell carcinoma arising in a dentigerous cyst.

PMID- 10935593
TI  - Meningioma of the parapharyngeal space: case report.

PMID- 10935594
TI  - Implant failure caused by screw head fractures--a new type of complication in a
      reconstruction plate: a case report.

PMID- 10935595
TI  - Unusual peripheral osteoma of the mandible: report of 2 cases.

PMID- 10935596
TI  - Endometrial carcinoma metastatic to the mandible: a case report.

PMID- 10935597
TI  - A new splint technique for anterior maxillary osteotomy under orotracheal
      intubation.

PMID- 10935598
TI  - The use of the Mitek Mini Anchor system in the hyoid suspension technique for the
      treatment of obstructive sleep apnea syndrome.

PMID- 10935599
TI  - Estimating the need for third molar removal.

PMID- 10935600
TI  - Challenges of the grid.

PMID- 10935601
TI  - Emissions targets 'unrealistic' says US climate change body

PMID- 10935602
TI  - Ensembl gets a Wellcome boost.

PMID- 10935604
TI  - Physicists celebrate detection of elusive 'final' particle

PMID- 10935603
TI  - Proposal for US patent office could help cut waiting time.

PMID- 10935605
TI  - Summit leaders fail to bridge GM food split.

PMID- 10935606
TI  - UK science plans spending spree.

PMID- 10935607
TI  - Legal protests prompt DNA primer release.

PMID- 10935608
TI  - Review panel assails Brussels research bureaucracy

PMID- 10935609
TI  - Call for North/South code of research ethics.

PMID- 10935610
TI  - Manhattan versus Reykjavik.

PMID- 10935611
TI  - How new technology put a coelacanth among the heirs of Piltdown Man.

PMID- 10935612
TI  - Assessors' odd listings don't inspire confidence.

PMID- 10935614
TI  - What if...?

PMID- 10935613
TI  - Reductionism should be clarified, not dismissed.

PMID- 10935616
TI  - How robust is the Internet?

PMID- 10935615
TI  - The bottle

PMID- 10935618
TI  - Deciphering methane's fingerprint

PMID- 10935617
TI  - Conducting the mitotic symphony.

PMID- 10935620
TI  - Global change. Silica control of carbon dioxide

PMID- 10935619
TI  - Fringe benefits to carbohydrates.

PMID- 10935621
TI  - Earth science. The extraterrestrial wedding ring

PMID- 10935622
TI  - Stem cells--hype and hope.

PMID- 10935623
TI  - Five plus two equals yellow.

PMID- 10935624
TI  - Climate change and constraints on breeding.

PMID- 10935625
TI  - Kinase regulation in inflammatory response.

PMID- 10935626
TI  - Fringe is a glycosyltransferase that modifies Notch.
AB  - Notch receptors function in highly conserved intercellular signalling pathways
      that direct cell-fate decisions, proliferation and apoptosis in metazoans. Fringe
      proteins can positively and negatively modulate the ability of Notch ligands to
      activate the Notch receptor. Here we establish the biochemical mechanism of
      Fringe action. Drosophila and mammalian Fringe proteins possess a fucose-specific
      beta1,3 N-acetylglucosaminyltransferase activity that initiates elongation of O
      linked fucose residues attached to epidermal growth factor-like sequence repeats
      of Notch. We obtained biological evidence that Fringe-dependent elongation of O
      linked fucose on Notch modulates Notch signalling by using co-culture assays in
      mammalian cells and by expression of an enzymatically inactive Fringe mutant in
      Drosophila. The post-translational modification of Notch by Fringe represents a
      striking example of modulation of a signalling event by differential receptor
      glycosylation and identifies a mechanism that is likely to be relevant to other
      signalling pathways.

PMID- 10935627
TI  - Characterizing the nonlinear growth of large-scale structure in the Universe
AB  - The local Universe displays a rich hierarchical pattern of galaxy clusters and
      superclusters. The early Universe, however, was almost smooth, with only slight
      'ripples' as seen in the cosmic microwave background radiation. Models of the
      evolution of cosmic structure link these observations through the effect of
      gravity, because the small initially overdense fluctuations are predicted to
      attract additional mass as the Universe expands. During the early stages of this
      expansion, the ripples evolve independently, like linear waves on the surface of
      deep water. As the structures grow in mass, they interact with each other in
      nonlinear ways, more like waves breaking in shallow water. We have recently shown
      how cosmic structure can be characterized by phase correlations associated with
      these nonlinear interactions, but it was not clear how to use that information to
      obtain quantitative insights into the growth of structures. Here we report a
      method of revealing phase information, and show quantitatively how this relates
      to the formation of filaments, sheets and clusters of galaxies by nonlinear
      collapse. We develop a statistical method based on information entropy to
      separate linear from nonlinear effects, and thereby are able to disentangle those
      aspects of galaxy clustering that arise from initial conditions (the ripples)
      from the subsequent dynamical evolution.

PMID- 10935628
TI  - Error and attack tolerance of complex networks
AB  - Many complex systems display a surprising degree of tolerance against errors. For
      example, relatively simple organisms grow, persist and reproduce despite drastic
      pharmaceutical or environmental interventions, an error tolerance attributed to
      the robustness of the underlying metabolic network. Complex communication
      networks display a surprising degree of robustness: although key components
      regularly malfunction, local failures rarely lead to the loss of the global
      information-carrying ability of the network. The stability of these and other
      complex systems is often attributed to the redundant wiring of the functional web
      defined by the systems' components. Here we demonstrate that error tolerance is
      not shared by all redundant systems: it is displayed only by a class of
      inhomogeneously wired networks, called scale-free networks, which include the
      World-Wide Web, the Internet, social networks and cells. We find that such
      networks display an unexpected degree of robustness, the ability of their nodes
      to communicate being unaffected even by unrealistically high failure rates.
      However, error tolerance comes at a high price in that these networks are
      extremely vulnerable to attacks (that is, to the selection and removal of a few
      nodes that play a vital role in maintaining the network's connectivity). Such
      error tolerance and attack vulnerability are generic properties of communication
      networks.

PMID- 10935629
TI  - Controlled surface charging as a depth-profiling probe for mesoscopic layers
AB  - Probing the structure of material layers just a few nanometres thick requires
      analytical techniques with high depth sensitivity. X-ray photoelectron
      spectroscopy (XPS) provides one such method, but obtaining vertically resolved
      structural information from the raw data is not straightforward. There are
      several XPS depth-profiling methods, including ion etching, angle-resolved XPS
      (ref. 2) and Tougaard's approach, but all suffer various limitations. Here we
      report a simple, non-destructive XPS depth-profiling method that yields accurate
      depth information with nanometre resolution. We demonstrate the technique using
      self-assembled multilayers on gold surfaces; the former contain 'marker'
      monolayers that have been inserted at predetermined depths. A controllable
      potential gradient is established vertically through the sample by charging the
      surface of the dielectric overlayer with an electron flood gun. The local
      potential is probed by measuring XPS line shifts, which correlate directly with
      the vertical position of atoms. We term the method 'controlled surface charging'
      and expect it to be generally applicable to a large variety of mesoscopic
      heterostructures.

PMID- 10935630
TI  - Signatures of granular microstructure in dense shear flows
AB  - Granular materials and ordinary fluids react differently to shear stresses.
      Rather than deforming uniformly, materials such as dry sand or cohesionless
      powders develop shear bands--narrow zones of large relative particle motion, with
      essentially rigid adjacent regions. Because shear bands mark areas of flow,
      material failure and energy dissipation, they are important in many industrial,
      civil engineering and geophysical processes. They are also relevant to
      lubricating fluids confined to ultrathin molecular layers. However, detailed
      three-dimensional information on motion within a shear band, including the degree
      of particle rotation and interparticle slip, is lacking. Similarly, very little
      is known about how the microstructure of individual grains affects movement in
      densely packed material. Here we combine magnetic resonance imaging, X-ray
      tomography and high-speed-video particle tracking to obtain the local steady
      state particle velocity, rotation and packing density for shear flow in a three
      dimensional Couette geometry. We find that key characteristics of the granular
      microstructure determine the shape of the velocity profile.

PMID- 10935631
TI  - Oscillatory cluster patterns in a homogeneous chemical system with global
      feedback
AB  - Oscillatory clusters are sets of domains in which nearly all elements in a given
      domain oscillate with the same amplitude and phase. They play an important role
      in understanding coupled neuron systems. In the simplest case, a system consists
      of two clusters that oscillate in antiphase and can each occupy multiple fixed
      spatial domains. Examples of cluster behaviour in extended chemical systems are
      rare, but have been shown to resemble standing waves, except that they lack a
      characteristic wavelength. Here we report the observation of so-called 'localized
      clusters'--periodic antiphase oscillations in one part of the medium, while the
      remainder appears uniform--in the Belousov-Zhabotinsky reaction-diffusion system
      with photochemical global feedback. We also observe standing clusters with fixed
      spatial domains that oscillate periodically in time and occupy the entire medium,
      and irregular clusters with no periodicity in either space or time, with standing
      clusters transforming into irregular clusters and then into localized clusters as
      the strength of the global negative feedback is gradually increased. By
      incorporating the effects of global feedback into a model of the reaction, we are
      able to simulate successfully the experimental data.

PMID- 10935632
TI  - Massive dissociation of gas hydrate during a Jurassic oceanic anoxic event
AB  - In the Jurassic period, the Early Toarcian oceanic anoxic event (about 183
      million years ago) is associated with exceptionally high rates of organic-carbon
      burial, high palaeotemperatures and significant mass extinction. Heavy carbon
      isotope compositions in rocks and fossils of this age have been linked to the
      global burial of organic carbon, which is isotopically light. In contrast,
      examples of light carbon-isotope values from marine organic matter of Early
      Toarcian age have been explained principally in terms of localized upwelling of
      bottom water enriched in 12C versus 13C (refs 1,2,5,6). Here, however, we report
      carbon-isotope analyses of fossil wood which demonstrate that isotopically light
      carbon dominated all the upper oceanic, biospheric and atmospheric carbon
      reservoirs, and that this occurred despite the enhanced burial of organic carbon.
      We propose that--as has been suggested for the Late Palaeocene thermal maximum,
      some 55 million years ago--the observed patterns were produced by voluminous and
      extremely rapid release of methane from gas hydrate contained in marine
      continental-margin sediments.

PMID- 10935633
TI  - Evidence for a late chondritic veneer in the Earth's mantle from high-pressure
      partitioning of palladium and platinum
AB  - The high-pressure solubility in silicate liquids of moderately siderophile 'iron
      loving' elements (such as nickel and cobalt) has been used to suggest that, in
      the early Earth, an equilibrium between core-forming metals and the silicate
      mantle was established at the bottom of a magma ocean. But observed
      concentrations of the highly siderophile elements--such as the platinum-group
      elements platinum, palladium, rhenium, iridium, ruthenium and osmium--in the
      Earth's upper mantle can be explained by such a model only if their metal
      silicate partition coefficients at high pressure are orders of magnitude lower
      than those determined experimentally at one atmosphere (refs 3-8). Here we
      present an experimental determination of the solubility of palladium and platinum
      in silicate melts as a function of pressure to 16 GPa (corresponding to about 500
      km depth in the Earth). We find that both the palladium and platinum metal
      silicate partition coefficients, derived from solubility, do not decrease with
      pressure--that is, palladium and platinum retain a strong preference for the
      metal phase even at high pressures. Consequently the observed abundances of
      palladium and platinum in the upper mantle seem to be best explained by a 'late
      veneer' addition of chondritic material to the upper mantle following the
      cessation of core formation.

PMID- 10935634
TI  - Mutation and sex in a competitive world.
AB  - How do deleterious mutations interact to affect fitness? The answer to this
      question has substantial implications for a variety of important problems in
      population biology, including the evolution of sex, the rate of adaptation and
      the conservation of small populations. Here we analyse a mathematical model of
      competition for food in which deleterious mutations affect competitive ability.
      We show that, if individuals usually compete in small groups, then competition
      can easily lead to a type of genetic interaction known as synergistic epistasis.
      This means that a deleterious mutation is most damaging in a genome that already
      has many other deleterious mutations. We also show that competition in small
      groups can produce a large advantage for sexual populations, both in mean fitness
      and in ability to resist invasion by asexual lineages. One implication of our
      findings is that experimental efforts to demonstrate synergistic epistasis may
      not succeed unless the experiments are redesigned to make them much more
      naturalistic.

PMID- 10935635
TI  - Long-term vocal recognition in the northern fur seal.
AB  - The ability to recognize and remember individual identities for long periods of
      time has important implications for the evolution of animal social behaviour,
      particularly complex interactions such as cooperation or mate choice. Despite
      this importance, there is only a single example of long-term individual
      recognition in nature, the 8-month retention of neighbour's song among male
      hooded warblers, Wilsonia citrina, and there is none for a non-human mammal.
      Associations between individuals spanning years, which are especially prevalent
      in carnivores, primates and seabirds, and evidence of mate fidelity provide
      indirect support for the ability of long-term recognition. In many of these
      instances, however, individuals do not separate for extended periods, and thus
      long-term recognition, although often assumed, may be both unnecessary and
      nonexistent. Furthermore, site fidelity rather than individual recognition may
      explain many instances of mate fidelity. Here I show that mother-offspring pairs
      of a migratory otariid pinniped--the northern fur seal (Callorhinus ursinus)--not
      only have the ability to recognize each other's vocalizations during the course
      of a breeding season, but are also able to retain these memories for at least 4
      years.

PMID- 10935636
TI  - State-dependent cross-inhibition between transmitter-gated cation channels.
AB  - Transmitter-gated cation channels are detectors of excitatory chemical signals at
      synapses in the nervous system. Here we show that structurally distinct
      alpha3beta4 nicotinic and P2X2 channels influence each other when co-activated.
      The activation of one channel type affects distinct kinetic and conductance
      states of the other, and co-activation results in non-additive responses owing to
      inhibition of both channel types. State-dependent inhibition of nicotinic
      channels is revealed most clearly with mutant P2X2 channels, and inhibition is
      decreased at lower densities of channel expression. In synaptically coupled
      myenteric neurons, nicotinic fast excitatory postsynaptic currents are occluded
      during activation of endogenously co-expressed P2X channels. Our data provide a
      molecular basis and a synaptic context for cross-inhibition between transmitter
      gated channels.

PMID- 10935637
TI  - Glycosyltransferase activity of Fringe modulates Notch-Delta interactions.
AB  - Ligands that are capable of activating Notch family receptors are broadly
      expressed in animal development, but their activity is tightly regulated to allow
      formation of tissue boundaries. Members of the fringe gene family have been
      implicated in limiting Notch activation during boundary formation, but the
      mechanism of Fringe function has not been determined. Here we present evidence
      that Fringe acts in the Golgi as a glycosyltransferase enzyme that modifies the
      epidermal growth factor (EGF) modules of Notch and alters the ability of Notch to
      bind its ligand Delta. Fringe catalyses the addition of N-acetylglucosamine to
      fucose, which is consistent with a role in the elongation of O-linked fucose O
      glycosylation that is associated with EGF repeats. We suggest that cell-type
      specific modification of glycosylation may provide a general mechanism to
      regulate ligand-receptor interactions in vivo.

PMID- 10935639
TI  - GATA3 haplo-insufficiency causes human HDR syndrome.
AB  - Terminal deletions of chromosome 10p result in a DiGeorge-like phenotype that
      includes hypoparathyroidism, heart defects, immune deficiency, deafness and renal
      malformations. Studies in patients with 10p deletions have defined two non
      overlapping regions that contribute to this complex phenotype. These are the
      DiGeorge critical region II (refs 1, 2), which is located on 10p13-14, and the
      region for the hypoparathyroidism, sensorineural deafness, renal anomaly (HDR)
      syndrome (Mendelian Inheritance in Man number 146255), which is located more
      telomeric (10p14-10pter). We have performed deletion-mapping studies in two HDR
      patients, and here we define a critical 200-kilobase region which contains the
      GATA3 gene. This gene belongs to a family of zinc-finger transcription factors
      that are involved in vertebrate embryonic development. Investigation for GATA3
      mutations in three other HDR probands identified one nonsense mutation and two
      intragenic deletions that predicted a loss of function, as confirmed by absence
      of DNA binding by the mutant GATA3 protein. These results show that GATA3 is
      essential in the embryonic development of the parathyroids, auditory system and
      kidneys, and indicate that other GATA family members may be involved in the
      aetiology of human malformations.

PMID- 10935638
TI  - Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic
      and lean.
AB  - Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial
      transporter superfamily that is expressed predominantly in skeletal muscle.
      However, its close relative UCP-1 is expressed exclusively in brown adipose
      tissue, a tissue whose main function is fat combustion and thermogenesis. Studies
      on the expression of UCP-3 in animals and humans in different physiological
      situations support a role for UCP-3 in energy balance and lipid metabolism.
      However, direct evidence for these roles is lacking. Here we describe the
      creation of transgenic mice that overexpress human UCP-3 in skeletal muscle.
      These mice are hyperphagic but weigh less than their wild-type littermates.
      Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The
      mice also exhibit lower fasting plasma glucose and insulin levels and an
      increased glucose clearance rate. This provides evidence that skeletal muscle UCP
      3 has the potential to influence metabolic rate and glucose homeostasis in the
      whole animal.

PMID- 10935640
TI  - A motif in the alphabeta T-cell receptor controls positive selection by
      modulating ERK activity.
AB  - Positive selection allows thymocytes that recognize an individual's own major
      histocompatibility complex (self-MHC) molecules to survive and differentiate,
      whereas negative selection removes overtly self-reactive thymocytes. Although
      both forms of thymic selection are mediated by the alphabeta T-cell receptor
      (TCR) and require self-MHC recognition, an important question is whether they are
      controlled by distinct signalling cascades. We have shown that mutation of an
      essential motif within the TCR alpha-chain-connecting peptide domain (alpha-CPM)
      profoundly affects positive but not negative selection. Using transgenic mice
      expressing a mutant alpha-CPM TCR we examined the contribution of several mitogen
      activated protein kinase (MAPK) cascades to thymic selection. Here we show that
      in thymocytes expressing a mutant alpha-CPM receptor, a positively selecting
      peptide failed to activate the extracellular signal-regulated kinase (ERK),
      although other MAPK cascades were induced normally. The defect in ERK activation
      was associated with impaired recruitment of the activated tyrosine kinases Lck
      and ZAP-70, phosphorylated forms of the TCR component CD3zeta and the adaptor
      protein LAT to detergent-insoluble glycolipid-enriched microdomains (DIGs).
      Therefore, an intact DIG-associated signalosome is essential for sustained ERK
      activation, which leads to positive selection.

PMID- 10935641
TI  - CD3delta couples T-cell receptor signalling to ERK activation and thymocyte
      positive selection.
AB  - Thymocytes from mice lacking the CD3delta chain of the T-cell receptor (TCR),
      unlike those of other CD3-deficient mice, progress from a CD4- CD8- double
      negative to a CD4+ CD8+ double-positive stage. However, CD3delta-/- double
      positive cells fail to undergo positive selection, by which double-positive cells
      differentiate into more mature thymocytes. Positive selection is also impaired in
      mice expressing inactive components of the Ras/mitogen activated protein (MAP)
      kinase signalling pathway. Here we show that CD3delta-/- thymocytes are defective
      in the induction of extracellular signal-regulated protein kinase (ERK) MAP
      kinases upon TCR engagement, whereas activation of other MAP kinases is
      unaffected. The requirement for CD3delta maps to its extracellular or
      transmembrane domains, or both, as expression of a tail-less CD3delta rescues
      both ERK activation and positive selection in CD3delta-/- mice. Furthermore, the
      defect correlates with severely impaired tyrosine phosphorylation of the linker
      protein LAT, and of the CD3zeta chain that is localized to membrane lipid rafts
      upon TCR engagement. Our data indicate that the blockade of positive selection of
      CD3delta-/- thymocytes may derive from defective tyrosine phosphorylation of
      CD3zeta in lipid rafts, resulting in impaired activation of the LAT/Ras/ERK
      pathway.

PMID- 10935642
TI  - Chfr defines a mitotic stress checkpoint that delays entry into metaphase.
AB  - Chemicals that target microtubules induce mitotic stress by affecting several
      processes that occur during mitosis. These processes include separation of the
      centrosomes in prophase, alignment of the chromosomes on the spindle in metaphase
      and sister-chromatid separation in anaphase. Many human cancers are sensitive to
      mitotic stress. This sensitivity is being exploited for therapy and implies
      checkpoint defects. The known mitotic checkpoint genes, which prevent entry into
      anaphase when the chromosomes are not properly aligned on the mitotic spindle,
      are, however, rarely inactivated in human cancer. Here we describe the chfr gene,
      which is inactivated owing to lack of expression or by mutation in four out of
      eight human cancer cell lines examined. Normal primary cells and tumour cell
      lines that express wild-type chfr exhibited delayed entry into metaphase when
      centrosome separation was inhibited by mitotic stress. In contrast, the tumour
      cell lines that had lost chfr function entered metaphase without delay. Ectopic
      expression of wild-type chfr restored the cell cycle delay and increased the
      ability of the cells to survive mitotic stress. Thus, chfr defines a checkpoint
      that delays entry into metaphase in response to mitotic stress.

PMID- 10935643
TI  - Humanized xenobiotic response in mice expressing nuclear receptor SXR.
AB  - The cytochrome CYP3A gene products, expressed in mammalian liver, are essential
      for the metabolism of lipophilic substrates, including endogenous steroid
      hormones and prescription drugs. CYP3A enzymes are extremely versatile and are
      inducible by many of their natural and xenobiotic substrates. Consequently, they
      form the molecular basis for many clinical drug-drug interactions. The induction
      of CYP3A enzymes is species-specific, and we have postulated that it involves one
      or more cellular factors, or receptor-like xeno-sensors. Here we identify one
      such factor unequivocally as the nuclear receptor pregnenolone X receptor (PXR)
      and its human homologue, steroid and xenobiotic receptor (SXR). We show that
      targeted disruption of the mouse PXR gene abolishes induction of CYP3A by
      prototypic inducers such as dexamethasone or pregnenolone-16alpha-carbonitrile.
      In transgenic mice, an activated form of SXR causes constitutive upregulation of
      CYP3A gene expression and enhanced protection against toxic xenobiotic compounds.
      Furthermore, we show that the species origin of the receptor, rather than the
      promoter structure of CYP3A genes, dictates the species-specific pattern of CYP3A
      inducibility. Thus, we can generate 'humanized' transgenic mice that are
      responsive to human-specific inducers such as the antibiotic rifampicin. We
      conclude that SXR/PXR genes encode the primary species-specific xeno-sensors that
      mediate the adaptive hepatic response, and may represent the critical biochemical
      mechanism of human xenoprotection.

PMID- 10935644
TI  - Pseudohyperplastic prostatic adenocarcinoma on needle biopsy and simple
      prostatectomy.
AB  - Prostatic adenocarcinoma resembling benign hyperplastic glands architecturally is
      a recently recognized entity. In the only prior study on this entity, 100 needle
      biopsies were studied and only two contained carcinoma with pseudohyperplastic
      features, which occupied a small percentage of the cancer. The current study
      investigates histologic attributes of pseudohyperplastic prostatic adenocarcinoma
      on needle biopsy and simple prostatectomy in which the pseudohyperplastic regions
      represent the majority of the cancer. The authors reviewed outside cases received
      in consultation by one of the authors (J.I.E.) and the surgical pathology files
      of Johns Hopkins Hospital from January 1991 to August 1998 and identified 20
      cases of needle biopsy and simple prostatectomy in which > or =60% of the cancer
      had benign architectural features. The majority (19 of 20) were consult cases. Of
      the 20 cases studied, 16 were needle biopsies, two were transurethral resections
      of the prostate, and two were enucleations. Cancer involved one core in 75% of
      the needle biopsies. In 13 of the 20 cases (65%), > or =90% of the cancer had
      pseudohyperplastic features. Benign features included papillary infoldings in all
      cases, large atypical glands in 95% of cases, branching in 45% of cases, and
      corpora amylacea in 20% of cases. The extent of pseudohyperplastic cancer ranged
      from 1.0 to 10.0 mm (average, 3.7 mm). Within the pseudohyperplastic foci,
      features helpful in establishing a malignant diagnosis were nuclear enlargement
      in 95% of cases, pink amorphous secretions in 70% of cases, occasional to
      frequent nucleoli in 45% of cases, and crystalloids in 45% of cases. Other
      features associated with malignancy (mitoses, blue-tinged mucin, adjacent high
      grade prostatic intraepithelial neoplasia, and perineural invasion) were seen
      infrequently. Immunohistochemical stains for high-molecular weight keratin showed
      an absence of basal cells in the pseudohyperplastic areas in all 20 cases,
      confirming the diagnosis of cancer. It is critical to recognize
      pseudohyperplastic prostatic adenocarcinoma and the features needed to establish
      a malignant diagnosis so these carcinomas are not misdiagnosed as benign.

PMID- 10935645
TI  - Benign lymphangioendothelioma (acquired progressive lymphangioma): a lesion not
      to be confused with well-differentiated angiosarcoma and patch stage Kaposi's
      sarcoma: clinicopathologic analysis of a series.
AB  - The clinicopathologic features of 12 cases of benign lymphangioendothelioma
      (acquired progressive lymphangioma) are reported. There were five male and seven
      female patients. Age at diagnosis ranged from 17 to 90 years (median age, 54
      yrs). Development of a single macular/papular hemangiomatous or pigmented lesion
      was the main presenting symptom. Symptom duration before diagnosis ranged from 2
      months to 20 years (median, 5.5 yrs). Tumor size ranged from 0.3 cm to 10 cm
      (median. 1.5 cm). Location included skin of the head and neck (n = 5), back (n =
      1), breast (n = 1), shoulder (n = 1), forearm (n = 1), plantar aspect of the foot
      (n = 2), and oral mucosa (n = 1). No patient had any other concomitant vascular
      anomaly (for example, lymphangiomatosis) or was suspected to have acquired
      immunodeficiency syndrome. Treatment consisted of excisional biopsy in nine
      patients, incisional biopsy in two, and wide excision in one. Follow-up
      information on nine patients (range, 4-40 mos; median, 12 mos) showed two local
      recurrences in one patient. Microscopically, the lesions consisted of
      anastomosing, often widely dilated vascular structures developing in the
      superficial dermis. As the lesion grew within deeper dermis, the vascular spaces
      collapsed and dissected the dermal collagen in an angiosarcoma-like pattern. The
      lining endothelium was flat and monolayered, with little or no cytologic atypia
      and no evident mitoses. Some vascular structures contained stromal papillary
      projections resembling papillary endothelial hyperplasia, and intravascular red
      blood cells were present occasionally. Immunohistochemistry performed in eight
      specimens showed variable endothelial cell reactivity for CD31 (7 of 8), CD34 (7
      of 7), and factor VIII-related antigen (4 of 6). A smooth muscle cell layer was
      observed focally around the vascular spaces in six lesions. Benign
      lymphangioendothelioma (acquired progressive lymphangioma) is an uncommon benign
      lesion that, in view of major differences in treatment and prognosis, should be
      distinguished from well-differentiated angiosarcoma and Kaposi's sarcoma,
      especially the patch stage and lymphangioma-like variants of the latter.

PMID- 10935646
TI  - Intraductal carcinoma of the breast: pathologic features associated with local
      recurrence in patients treated with breast-conserving therapy.
AB  - Local excision and radiation therapy is a standard treatment option for duct
      carcinoma in situ (DCIS) of the breast. There is no consensus regarding the
      significant histologic features associated with recurrence. The authors studied a
      large group of patients with mammographically detected DCIS treated with breast
      conserving therapy to explore DCIS volume relationships, DCIS features, specimen
      characteristics, and the effect of patient age at diagnosis. Thirteen patients
      (10%) developed a recurrent carcinoma in the ipsilateral breast, resulting in 5-
      and 10-year actuarial recurrence rates of 8.9% and 10.3%, respectively. Local
      recurrences were identified as a true recurrence/marginal miss (TR/MM) in nine
      patients, and elsewhere in the breast in four patients. The notable features
      associated with TR/MM recurrences on univariate analysis included patient age
      less than 45 years old, six or more slides with DCIS, no microscopic
      calcifications within DCIS ducts, and five or more DCIS ducts or terminal duct
      lobular units (TDLUs) with cancerization of lobules (COL) within 0.42 cm of the
      final surgical margin. DCIS tumor size, nuclear grade, amount of central
      necrosis, and margin status were not associated with outcome. Multivariate
      analysis found that the absence of microcalcifications within DCIS ducts, patient
      age, number of slides with DCIS or TDLUs with COL, and the number of DCIS ducts
      or TDLUs with COL within 0.42 cm of the final margin were related significantly
      to TR/MM recurrence. Patients with a total of six or more slides with DCIS, or
      who have 11 or more DCIS ducts or TDLUs with COL near the final margin are at
      increased risk of having a substantial volume of residual DCIS in the adjacent
      unexcised breast. These results suggest that the volume of DCIS in the specimen,
      and the volume of DCIS near the margin are associated with local recurrence.
      These features can be used to identify those patients with a higher chance of
      local recurrence.

PMID- 10935647
TI  - Lymphocyte predominance Hodgkin's disease: the use of bcl-6 and CD57 in diagnosis
      and differential diagnosis.
AB  - Distinction of lymphocyte predominance Hodgkin's disease (LPHD) from other forms
      of lymphoma often requires immunohistochemistry (IHC). Most previously published
      recommended panels include markers to define the large neoplastic cells (for
      example, CD20, J chain, CD45) as well as the non-neoplastic background cells
      (CD21, CD45RO, CD57, TiA 1). In the present study we examine the practical use of
      a double IHC method designed to look simultaneously at two germinal center
      specific cell types: bcl6+ cells and [bc16+, CD57+] co-positive cells. All 10
      nodular LPHD had bcl6+ large cells and numerous CD57+ small background cells,
      including [bcl6+CD57+] cells in rosettes. One case of LPHD with large cell
      transformation contained numerous bcl6+ large cells both singly (in areas of
      typical LPHD) and in sheets (in foci of large cell transformation), many CD57+
      small cells but few [bcl6+CD57+] co-positive cells and no rosettes. In none of
      the five cases of florid progressive transformation of germinal centers were true
      rosettes seen, although all contained variable numbers of bcl6+ large cells and
      CD57+ cells. Lymphocyte-rich classic Hodgkin's disease LRCHD cases were notable
      for bcl6 reactivity in Reed-Sternberg cells in all cases, numerous background
      small bcl6+ lymphocytes, and rare CD57+ cells. Two phenotypic profiles were
      associated with the 10 cases of T cell-rich B cell large cell lymphoma (TCRBCL).
      In the first, group "A," six of six cases had bc16- large cells and few CD57+
      small cells, and none had significant numbers of [bcl6+, CD57+] co-positive
      cells. In the second, group "B," four of four cases had bcl6+ large cells with
      numerous CD57+ and [bcl6+, CD57+] co-positive cells. These findings not only show
      that LPHD can be distinguished from its morphologic mimics through identification
      of specific germinal center cell types, but also identifies a second group of
      TCRBCL (group "B") whose phenotype suggests it might be an architectural variant
      of nodular LPHD.

PMID- 10935648
TI  - Dedifferentiated clear cell chondrosarcoma.
AB  - Dedifferentiation, a change in the histologic character and clinical behavior of
      a tumor to a more immature and aggressive one, occurs in approximately 11% of all
      chondrosarcomas. The original lesion is usually a low-grade chondrosarcoma. Clear
      cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy with a
      preference for the ends of long bones. It is usually curable by resection.
      Recurrence commonly follows inadequate surgery, and metastases to lung, brain,
      and bones can develop. However, dedifferentiation has not yet been described in
      association with clear cell chondrosarcoma. Three patients are described who were
      initially diagnosed as having clear cell chondrosarcoma of the femur. Two were
      treated with en bloc resection for a clear cell chondrosarcoma. One of these had
      an undifferentiated sarcoma in a local recurrence after 6 years. In the second,
      metastasis of the clear cell chondrosarcoma developed 5(1/2) years after surgery;
      autopsy revealed undifferentiated sarcoma in the lung, heart, and lumbar spine.
      The third patient had dedifferentiated clear cell chondrosarcoma at the time of
      resection following the biopsy diagnosis of clear cell chondrosarcoma. All three
      died with metastatic disease. These three patients represent three different
      manifestations of dedifferentiation-at initial diagnosis, at recurrence, and at
      metastasis. To our knowledge, this is the first description of dedifferentiation
      occurring in clear cell chondrosarcoma.

PMID- 10935649
TI  - Primary renal synovial sarcoma: molecular and morphologic delineation of an
      entity previously included among embryonal sarcomas of the kidney.
AB  - We report 15 primary renal neoplasms with morphologic, immunohistochemical, and
      molecular features identical to those of synovial sarcoma. These tumors form a
      distinct subset of the entity previously designated as embryonal sarcoma of the
      kidney. Most were diagnosed between the ages of 20 and 50 years. On gross
      examination, tumors are large, partially necrotic, and usually contain smooth
      walled cysts. Microscopically, tumors are characterized by mitotically active,
      monomorphic plump spindle cells with indistinct cell borders growing in short,
      intersecting fascicles. Grossly identified cysts are lined by mitotically
      inactive polygonal eosinophilic cells with apically oriented nuclei ("hobnailed
      epithelium"). The spindle cells are immunoreactive for vimentin, often
      immunoreactive for EMA, but typically non-immunoreactive for desmin, actin, S100,
      or cytokeratins, whereas the cyst epithelium is cytokeratin-positive. These
      findings are consistent with monophasic, spindled synovial sarcoma encircling
      dilated native renal collecting ducts. The presence of an SYT-SSX gene fusion
      resulting from the t(X;18) characteristic of synovial sarcoma was demonstrated by
      reverse transcriptase polymerase chain reaction in three of three tumors in which
      adequate RNA could be obtained from paraffin blocks. An additional case
      demonstrated the characteristic t(X; 18) translocation on cytogenetic analysis,
      but adequate material to perform molecular studies was not available in this case
      or the remaining 11 cases. Primary renal synovial sarcoma is a distinctive
      clinicopathologic entity confirmed by molecular detection of SYT-SSX fusion
      transcripts.

PMID- 10935650
TI  - Primary synovial sarcoma of the kidney.
AB  - The authors present two cases of primary synovial sarcoma of the kidney. Both
      patients had a mass in the upper part of the right kidney without any primary
      extrarenal neoplastic lesions. Grossly, the tumors were soft to rubbery masses
      measuring 5.5 cm and 5 cm in diameter, respectively. Histologically, both tumors
      were poorly differentiated synovial sarcoma. The lesions exhibited a
      hypercellular solid or lobular growth of round, oval, or short spindle cells in
      variably solid sheets, in intersecting fascicles, or in a haphazard fashion.
      Areas of solid aggregation or fascicles of the tumor cells alternating with
      hypocellular myxoid tissues, together with areas displaying a prominent
      hemangiopericytoma-like pattern, were found. Immunohistochemically, vimentin was
      diffusely positive and a few tumor cells were positive for cytokeratin,
      epithelial membrane antigen, and neurofilament. The tumor cells were negative for
      S- 100 protein, CD34, smooth muscle actin, and desmin, whereas CD56 and CD99 were
      positive. In both cases, reverse transcription-polymerase chain reaction using
      ribonucleic acid extracted from formalin-fixed, paraffin-embedded tissues
      detected SYT-SSX2 fusion gene transcripts, which are characteristic molecular
      findings of synovial sarcoma. One patient died 10 months after diagnosis. These
      tumors are unique cases of primary synovial sarcoma of the kidney confirmed by
      molecular study.

PMID- 10935651
TI  - Pulmonary and mediastinal glomus tumors--report of five cases including a
      pulmonary glomangiosarcoma: a clinicopathologic study with literature review.
AB  - Pulmonary and mediastinal glomus tumors are rare lesions, with four previously
      reported primary pulmonary cases and three mediastinal cases. The authors report
      one mediastinal glomus tumor, a locally infiltrative type, and four pulmonary
      glomus tumors, including the first case of primary pulmonary glomangiosarcoma.
      These tumors show a variety of clinical and pathologic differences from the more
      common cutaneous variety, including later age at presentation, larger size, and
      more frequent atypical/malignant features. Mediastinal and pulmonary glomus
      tumors both have an average patient age at presentation of 45 years. However,
      compared with their pulmonary counterparts, mediastinal glomus tumors are less
      common, more often symptomatic, and are larger (average size, 5.4 cm).
      Additionally, mediastinal glomus tumors more often demonstrate malignant or
      atypical features. Pulmonary glomus tumors average 3.3 cm in greatest dimension,
      with the majority measuring less than 2.5 cm. The pulmonary glomangiosarcoma
      presented was large, measuring 9.5 cm, and showed increased mitotic count (9
      mitoses/10 high-power fields), necrosis, cytologic atypia, and was associated
      with disseminated disease. Regardless of clinical symptoms, histologic features,
      and even metastases, the vast majority of all benign and malignant glomus tumors
      are indolent and cured surgically, with adjuvant therapy needed only for
      occasional patients with more advanced disease. The four patients with glomus
      tumors reported are currently alive and free of disease as of last follow up. The
      patient with the glomangiosarcoma developed widespread metastases and died of
      disease 68 weeks after initial therapy.

PMID- 10935653
TI  - Sarcomas arising in dermatofibrosarcoma protuberans: a reappraisal of biologic
      behavior in eighteen cases treated by wide local excision with extended clinical
      follow up.
AB  - There is a prevailing view that sarcomas arising in dermatofibrosarcoma
      protuberans (DFSP) have a higher risk of metastasis than ordinary DFSP, but these
      data are based on cases with variable and often suboptimal treatment. There has
      not been a large study of sarcomas arising in DFSP in which all cases were
      treated by wide local excision, thereby arguably altering outcome.
      Clinicopathologic features of 18 cases of sarcomas arising in DFSP treated by
      wide local excision and having follow up of at least 5 years were analyzed. An
      estimate of the proportion of sarcoma and DFSP was made. The number of mitotic
      figures and degree of CD34 immunoreactivity were assessed in each case. The
      cohort included 13 females and 5 males (age, 23-87 yrs; median, 47 yrs). The
      tumors involved the trunk (7), scalp (4), extremities (4), and inguinal region
      (3), and ranged from 1.5 to 7 cm (median, 4 cm). Sarcoma occurred de novo in 15
      cases and in a recurrence in three. Sarcomas resembled fibrosarcoma (17) or
      malignant fibrous histiocytoma (1) and occupied between 20% and 80% of the tumor
      (median, 60%). Mitotic activity ranged from 2 to 16 per 10 high-power field (HPF;
      median 7 per 10 HPF) in the sarcomatous component and 0 to 3 per 10 HPF (median,
      1 per 10 HPF) in the DFSP component. All tumors expressed CD34 in the DFSP
      component but only nine (50%) in the sarcomatous component. All patients were
      treated by wide local excision with negative margins; three additionally received
      radiation. Four patients (22%) developed recurrences, but none developed
      metastasis during the follow-up period of 62 months to 17 years (median, 81.5
      mos). In contrast to earlier studies, we demonstrate that patients with sarcomas
      arising in DFSP do not have an increased risk of distant metastasis within a 5
      year follow-up period, provided they are treated by wide local excision with
      negative margins. This probably reflects the fact that wide local excision
      results in eradication of local tumor, thereby eliminating the source for
      subsequent dissemination. However, we cannot completely exclude the possibility
      that tumors in which clear margins are achieved represent a less aggressive
      subset, as has been suggested for high-grade extremity sarcomas. Previous studies
      showing increased metastasis for sarcomas arising in DFSP should be re-evaluated
      to determine if, with treatment stratification, metastatic rate varies.

PMID- 10935652
TI  - Comparative studies of the colonic in situ expression of intercellular adhesion
      molecules (ICAM-1, -2, and -3), beta2 integrins (LFA-1, Mac-1, and p150,95), and
      PECAM-1 in ulcerative colitis and Crohn's disease.
AB  - A dysregulated local immune defense with a constant influx of leukocytes provides
      a basis for continuous intestinal inflammation in ulcerative colitis (UC) and
      Crohn's disease (CD). Cell adhesion molecules are pivotal for the migration of
      leukocytes from the circulation toward the colonic epithelium. A study
      quantifying the cells expressing intercellular adhesion molecules (ICAMs), beta2
      integrins, and platelet-endothelial cell adhesion molecule-1 (PECAM-1) in the
      colon was performed to illustrate the leukocyte migration pathway in inflammatory
      bowel disease. Serial colonic sections (10 UC, 10 CD, and 10 controls) were
      stained immunohistochemically for ICAM-1, ICAM-2, ICAM-3, CD11a, CD11b, CD18, and
      PECAM-1. Cell adhesion molecule expression was evaluated quantitatively with
      reference to topographic localization. In UC, polymorphonuclear leukocytes (PMNs)
      in contact with the crypt epithelium and in crypt abscesses expressed CD11b. CD
      tissue was characterized by CD11a-, CD11c-, and ICAM-1-expressing cells. ICAM-1
      was detected on endothelial cells, leukocytes, and apical parts of epithelial
      membranes, whereas ICAM-2 was expressed on basal epithelial membranes. Most
      infiltrating leukocytes expressed ICAM-3, whereas perivascular mononuclear cells
      expressed PECAM-1. Interestingly, the epithelial basement membrane in UC stained
      for CD18. In conclusion, CD11b, CD18, and ICAM-2 seem to be important for PMN
      transepithelial migration in UC, whereas CD11a, CD11c, ICAM-1, and ICAM-3 seem
      central in leukocyte locomotion and aggregation in CD. Differentiated
      upregulation of cell adhesion molecules is suggested to be essential for the
      diversities between UC and CD.

PMID- 10935654
TI  - Evidence for the neoplastic transformation of Von-Meyenburg complexes.
AB  - Von-Meyenburg complexes (VMC) are seen frequently in the liver and are largely
      considered to be innocuous, with only 11 cases reported in the literature of
      neoplastic transformation of VMCs. The authors report three cases of
      cholangiocarcinoma, each occurring in a background of fibrosis and nodularity
      that was reported initially as micronodular cirrhosis. Although the livers showed
      cirrhosis, the central veins were often preserved, and regenerative activity was
      patchy and focal. Histologic examination revealed many VMCs, and a gradual
      transition from VMCs to hyperplastic or adenomatous lesions and
      cholangiocarcinoma. The adenomatous lesions consisted of extensive replacement of
      the parenchyma by tumor-like nodules of ductular proliferations without obvious
      features of malignancy. All three patients were older than 60 years of age and
      had portal hypertension. Computed tomographic scans showed multiple, small renal
      cysts in one patient. Immunohistochemical staining showed positivity for
      epithelial membrane antigen, carcinoembryonic antigen, and keratins (AE1/AE3 and
      CAM5.2) in tumor cells, consistent with cholangiocarcinoma. The pattern of
      fibrosis and nodularity in these cases is not typical of either congenital
      hepatic fibrosis or usual cirrhosis. The authors propose that these patients
      represent another aspect in the spectrum of ductal plate malformations that may
      be modified by other factors such as alcohol, drugs, or infection. To their
      knowledge, neoplastic transformation of VMCs in the background of such changes
      has never been reported before.

PMID- 10935655
TI  - HMB-45 immunohistochemical staining of sentinel lymph nodes: a specific method
      for enhancing detection of micrometastases in patients with melanoma.
AB  - Despite the profound therapeutic and prognostic implications of nodal metastases
      in patients with melanoma, there is no consensus strategy for the optimal
      detection of metastases in sentinel lymph node biopsies. Traditional microscopic
      examination may be too crude to detect scattered, individual tumor cells.
      Conversely, molecular genetic techniques are prone to false-positive results. The
      authors evaluated the ability of HMB-45 immunohistochemistry to enhance detection
      of melanoma cells in histologically negative sentinel lymph nodes. Ninety-six
      sentinel lymph nodes, collected over a 25-month period from 66 consecutive
      patients with melanoma, were processed routinely and sectioned serially. Slides
      1, 3, and 5 were stained with hematoxylin and eosin. HMB-45 staining was
      performed on an intervening slide in histologically negative nodes. To assess the
      background incidence of HMB-45-positive cells in lymph nodes draining the skin,
      the authors stained 244 cervical and axillary lymph nodes from patients without
      melanoma. Metastases were apparent microscopically in 12 (18%) of the 66 patients
      with melanoma. Of the remaining 54 patients, four patients (7%) had lymph nodes
      harboring individual, scattered HMB-45-positive cells. Benign nevocellular
      aggregates were present in four of the 96 sentinel lymph nodes (4% nodal
      incidence), but they were HMB-45-negative. The authors did not observe a single
      HMB-45-positive cell in the 244 lymph nodes from patients without melanoma.
      Immunohistochemistry appears to represent a specific means of enhancing tumor
      detection in sentinel lymph nodes from patients with melanoma.

PMID- 10935656
TI  - Pulmonary cytolytic thrombi: a previously unrecognized complication of bone
      marrow transplantation.
AB  - Lung injury is a frequent and severe complication of bone marrow transplantation
      (BMT). Over the past 5 years we have recognized a new noninfectious pulmonary
      complication of allogeneic BMT in 12 patients, presenting with fever, pulmonary
      nodules on chest computed tomography, and distinctive histopathologic appearance
      descriptively termed "pulmonary cytolytic thrombi" (PCT). All but one patient
      were children transplanted for malignant (9) and nonmalignant (3) conditions. Ten
      of the patients had active graft-versus-host disease (GVHD) of skin, bowel, or
      both at the time of diagnosis of the PCT. In all cases occlusive vascular lesions
      were present, most of them associated with hemorrhagic infarcts. The endothelial
      cell layer was discontinuous in all cases stained with antibody to CD31. The
      thrombi had entrapped recognizable leukocytes and CD45-positive cell fragments
      embedded in a tenacious basophilic material. The symptoms and radiologic findings
      resolved in weeks to months. PCT may represent a previously unrecognized form of
      pulmonary acute GVHD.

PMID- 10935657
TI  - The nature of the myenteric infiltrate in achalasia: an immunohistochemical
      analysis.
AB  - Achalasia is an esophageal motor disorder characterized by abnormal relaxation of
      the lower esophageal sphincter and absence of progressive peristalsis in the
      esophageal body. Previous studies evaluating esophagomyotomy and esophageal
      resection specimens have shown the presence of myenteric inflammation to be a
      consistent and early pathologic change in patients with achalasia. Thus, the goal
      of this study was to determine the immunohistochemical characteristics of the
      inflammatory infiltrate within the myenteric plexus in patients with clinically
      early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the
      immunohistochemical features of the myenteric lymphocytes using antibodies that
      recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation
      state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with
      clinically early achalasia who underwent esophagomyotomy and 13 patients with
      clinically endstage achalasia who underwent esophageal resection. The myenteric
      infiltrate in all nine esophagomyotomy specimens was composed predominantly of T
      cells (CD3-positive), the majority of which also stained for CD8. In five of nine
      specimens, the majority of CD8-positive cells stained for TIA-1. In the
      esophageal resection specimens, the myenteric infiltrate was composed
      predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there
      was a predominance of CD20-positive B cells, and in the remaining three cases
      there were relatively equal numbers of T and B cells. In eight of 13 cases, the
      majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the
      majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and
      esophageal resection specimens studied, rare granzyme B-positive cells were
      detected. In conclusion, the majority of myenteric inflammatory cells in patients
      with achalasia are CD3-positive T cells, most of which are also CD8-positive,
      although the relative percentage of such cells appears to decrease with disease
      progression. Furthermore, many of the CD3-positive/CD8-positive myenteric
      lymphocytes also express TIA-1, suggesting they are resting or activated
      cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a
      subpopulation of these cells supports the contention that achalasia is an immune
      mediated disease, although the inciting antigen remains an enigma.

PMID- 10935658
TI  - Metastasizing mixed tumor of the parotid: initial presentation as a solitary
      kidney tumor and ultimate carcinomatous transformation at the primary site.
AB  - Benign mixed tumors of the salivary glands are generally regarded as indolent and
      harmless neoplasms. A subset of benign mixed tumors, however, can undergo
      carcinomatous transformation (that is, carcinoma ex-mixed tumor). Even more
      rarely, a mixed tumor that is seemingly benign at the microscopic level will
      metastasize like a true carcinoma (that is, metastasizing mixed tumor [MZMT]).
      Despite the benign appearance of the metastatic implants, there is usually little
      doubt regarding their true nature and origin. Patients invariably have had a
      mixed tumor removed from the parotid or some other salivary gland, and metastatic
      spread is usually preceded by multiple episodes of local tumor recurrence. We
      report a case of MZMT that presented as a solitary kidney mass. In the absence of
      a previous or concurrent salivary gland tumor, its metastatic nature was not
      appreciated and it was regarded as an unusual but benign kidney adenoma. One year
      after removal of the kidney mass, the patient presented with signs and symptoms
      of an aggressive parotid tumor. Pathologic examination of the tumor in the
      parotid demonstrated a high-grade carcinoma arising from a mixed tumor. This case
      underscores the importance of considering MZMT when a seemingly benign mixed
      tumor is encountered at a nonsalivary site, even in patients without a supportive
      history. Failure to do so may cause an unnecessary delay in primary tumor
      diagnosis and management, allow the primary tumor to progress toward a more
      malignant phenotype, and deny the patient a high expectation for a complete cure.

PMID- 10935659
TI  - Local spread of melanomas.

PMID- 10935660
TI  - Scanning of gross specimens.

PMID- 10935661
TI  - The esophagogastric junction.

PMID- 10935662
TI  - Cytokeratins in round cell sarcomas.

PMID- 10935663
TI  - Primary giant cell tumors of soft tissue.

PMID- 10935665
TI  - Is albumin mRNA detection in the diagnosis of hepatocellular carcinoma better
      than existing markers?

PMID- 10935666
TI  - Deciduoid or pseudodecidual mesothelioma.

PMID- 10935667
TI  - Perindopril for elderly people with chronic heart failure: the PEP-CHF study. The
      PEP investigators.
AB  - BACKGROUND: The prevalence of chronic heart failure (CHF) rises with increasing
      age, from < 1% in those below 65 years of age to > 5% in those over 65 years of
      age and is a major cause of morbidity and mortality in older people. Recent
      European guidelines point to a major deficiency in our knowledge of how to treat
      diastolic chronic heart failure, and a lack of information on treatment for heart
      failure in the elderly in general. AIMS: The aims of this trial are to assess the
      potential benefits of the ACE inhibitor perindopril to treat chronic heart
      failure in elderly people, in the absence of any major left ventricular systolic
      dysfunction. SUBJECTS: One thousand people over the age of 70 years will be
      recruited into this study. Evidence of chronic heart failure will be confirmed by
      clinical criteria and echocardiography. METHODS: Once a diagnosis of chronic
      heart failure has been confirmed, the patient will receive either perindopril or
      placebo in addition to their usual treatment. Death, and unplanned heart failure
      related hospitalisations, are the primary outcomes. Quality of life, as measured
      by the Guyatt questionnaire will be assessed at the beginning of the study and at
      1 year. Sub-studies of this trial include a 6-min walking test and more detailed
      evaluation of ventricular function (as assessed by echocardiography). Both
      parameters will be measured at 8 weeks and 1 year, and analysed against baseline
      data. Cognitive function in this group of patients will also be evaluated at
      baseline and 1 year. This trial is due to report in the year 2001.

PMID- 10935668
TI  - Effects of systematic education on heart failure patients' knowledge after 6
      months. A randomised, controlled trial.
AB  - BACKGROUND: Many procedures for patient education are introduced in clinical
      practice without proper evaluation in randomised trials. AIMS: To compare
      systematic nurse and pharmacist led education including an interactive Kodak
      Photo-CD Portfolio technique with conventional information regarding heart
      failure patients' knowledge. METHODS: One hundred and thirty heart failure
      patients discharged from hospital were randomised to receive either conventional
      information or additional structured education with a follow-up of 6 months.
      Difference in knowledge was tested by questionnaire after 6 months. RESULTS: At
      the end of the study there was a significant difference in the intervention group
      (n = 50) compared to the control group (n = 58) regarding knowledge as tested by
      a questionnaire. Of maximal 28 points the intervention group attained 17.2 points
      (mean) and the control group 14.3 points (mean), 95% confidence interval for
      difference 1.0-4.7 points (P = 0.0051). CONCLUSIONS: Two to 3 hours of systematic
      education improved heart failure patients' knowledge on essential issues. High
      age does not preclude the introduction of a new technique for patient education.

PMID- 10935669
TI  - Is the prognosis of heart failure improving?
AB  - BACKGROUND AND METHODS": Heart failure is common and effective therapy exists but
      as yet there is little evidence that the overall prognosis is improving in
      clinical practice. We sought to determine if mortality, re-admission with heart
      failure and re-admission for any cause, had changed between cohorts of first-time
      admissions for heart failure identified in 1984, 1988 and 1992 using linked
      hospital discharge and mortality data from Scotland (population approximately 5
      million). FINDINGS: The number of first-time admissions for heart failure
      increased by 30% between 1984 and 1992, from 9716 to 12640. Their mean age was 74
      years and 54% were women. Over the same period 3-year mortality declined in
      patients < 65 years from 53 to 41% (reduction in risk 12% (95% confidence
      interval 9-15%. Log-rank 70.0; P<0.001) and for patients > or =65 years from 71%
      to 66% (reduction in risk 5% (95% confidence interval 3-6%. Log-rank 74.5;
      P<0.0001). Time to death or first re-admission with heart failure also improved
      but not time to death or first re-admission for any cause. The total number of re
      admissions increased between 1984 and 1992 but bed-days occupancy for heart
      failure and for any cause, adjusted for days alive, declined due to a reduction
      in length of stay. INTERPRETATION: These data suggest that the prognosis of
      patients with a first admission for heart failure is improving. The timing of
      improvement coincides with the gradual increase in the use of angiotensin
      converting enzyme inhibitors for heart failure although a causal link cannot be
      proved from these data.

PMID- 10935670
TI  - Increased soluble platelet/endothelial cellular adhesion molecule-1 and
      osteonectin levels in patients with severe congestive heart failure. Independence
      of disease etiology, and antecedent aspirin therapy.
AB  - BACKGROUND: Platelet-endothelial interactions modulated by adhesion molecules,
      may play an important role in the pathogenesis of congestive heart failure (CHF).
      Soluble levels of these molecules and platelet-derived substances are reportedly
      elevated in patients with CHF. However, no data are available on the plasma
      levels of Platelet/Endothelial Cell Adhesion Molecule-1 (PECAM-1), and platelet
      derived osteonectin in this growing population. METHODS AND RESULTS: Soluble
      levels by ELISA were prospectively determined in patients with severe CHF (n =
      37) and correlated to etiology and antecedent aspirin use, and compared with 14
      healthy control subjects. Left ventricular dysfunction was attributed to
      idiopathic dilated cardiomyopathy in 18 and coronary artery disease in 19
      patients. Twenty-one patients were aspirin-free and 16 patients were using
      aspirin (81-500 mg daily). Elevated soluble PECAM-1 (51.31+/-2.44 ng/ml, P =
      0.0001), and osteonectin (826.27+/-22.37 ng/ml, P = 0.0001) were observed in
      patients with CHF, as compared to healthy controls (32.56+/-1.21 ng/ml, and
      478.02+/-31.32 ng/ml, respectively). Neither etiology of CHF, nor antecedent
      aspirin therapy significantly affects the levels of PECAM-1 or osteonectin.
      CONCLUSIONS: Despite long-term aspirin therapy and independently of the etiology
      of the disease, soluble PECAM-1 and osteonectin were elevated in the majority of
      patients with severe CHF, suggesting platelet-endothelial activation. The present
      data provide additional evidence that more potent anti-platelet and endothelial
      preservation regimens deserve further study in the heart failure population.

PMID- 10935671
TI  - Tailored therapy to hemodynamic goals for advanced heart failure.

PMID- 10935672
TI  - Beta-blockers for advanced heart failure--how far can you go?

PMID- 10935673
TI  - Ambulatory vasodilator therapy in heart failure: systematic review of the
      literature and personal observational experience.

PMID- 10935674
TI  - Revascularisation for chronic heart failure: a valid option?

PMID- 10935675
TI  - Pacing for heart failure: selection of patients, techniques and benefits.

PMID- 10935676
TI  - Do we have reasons to be enthusiastic about pacing to treat advanced heart
      failure?

PMID- 10935677
TI  - Left ventricular assist devices--reasons to be enthusiastic.

PMID- 10935678
TI  - Plasma viscosity and fibrinogen in relation to haemodynamic findings in chronic
      congestive heart failure.
AB  - The aim of this study was to investigate an inflammatory response indicated by
      fibrinogen and plasma viscosity in relation to haemodynamic and clinical findings
      of patients with stable CHF due to coronary heart disease (CHD).

PMID- 10935679
TI  - Effects of resistive breathing on exercise capacity and diaphragm function in
      patients with ischaemic heart disease.
AB  - BACKGROUND: Muscle weakness has been suggested to result from the deconditioning
      that accompanies decreased activity levels in chronic cardiopulmonary diseases.
      The benefits of standard exercise programmes on exercise capacity and muscular
      strength in disease and health are well documented and exercise capacity is a
      significant predictor of survival in patients with chronic heart failure (CHF).
      Selective respiratory muscle training has been shown to improve exercise
      tolerance in CHF and such observations have been cited to support the suggestion
      that respiratory muscle weakness contributes to a reduced exercise capacity
      (despite biopsies showing the metabolic profile of a well trained muscle). AIMS:
      This study aimed to determine the effects of selective inspiratory muscle
      training on patients with chronic coronary artery disease to establish if an
      improved exercise capacity can be obtained in patients that are not limited in
      their daily activities. METHODS: Nine male patients performed three exercise
      tests (with respiratory and diaphragm function assessed before the third test)
      then undertook a 4-week programme of inspiratory muscle training. Exercise
      tolerance, respiratory and diaphragmatic function were re-assessed after
      training. RESULTS: Exercise capacity improved from 812+/-42 to 864+/-49 s,
      P<0.05, and velocity of diaphragm shortening increased (during quiet breathing
      from 12.8+/-1.6 to 19.4+/-1.1 mm s(-1), P<0.005, and sniffing from 71.9+/-9.4 to
      110.0+/-12.3 mm s(-1), P<0.005). In addition, five from nine patients were
      stopped by breathlessness before training; whereas only one patient was stopped
      by breathlessness after training. CONCLUSION: The major findings in this study
      were that a non-intensive 4-week training programme of resistive breathing in
      patients with chronic coronary artery disease led to an increase in exercise
      capacity and a decrease in dyspnoea when assessed by symptom limited exercise
      testing. These changes were associated with significant increases in the velocity
      of diaphragmatic excursions during quiet breathing and sniffing. Patients that
      exhibited small diaphragmatic excursions during quiet breathing were most likely
      to improve their exercise capacity after the training programme. However, the
      inspiratory muscle-training programme was not associated with any significant
      changes in respiratory mechanics when peak flow rate, forced expiratory volume
      and forced vital capacity were measured. The resistive breathing programme used
      here resulted in a significant increase in the velocity of diaphragm movement
      during quiet breathing and sniffing. In other skeletal muscles, speed of
      contraction can be determined by the relative proportion of fibre types and
      muscle length (Jones, Round, Skeletal Muscle in Health and Disease. Manchester:
      University Press, 1990). The intensity of the training programme used here,
      however, is unlikely to significantly alter muscle morphology or biochemistry.
      Short-term training studies have shown that there can be increases in strength
      and velocity of shortening that do not relate to changes in muscle biochemistry
      or morphology. These changes are attributed to the neural adaptations that occur
      early in training (Northridge et al., Br. Heart J. 1990; 64: 313-316).
      Independent of the mechanisms involved, this small, uncontrolled study suggests
      that inspiratory muscle training may improve exercise capacity, diaphragm
      function and symptoms of breathlessness in patients with chronic coronary artery
      disease even in the absence of heart failure.

PMID- 10935681
TI  - How the medical system manages patients with suspected or confirmed heart failure
      in Hungary.

PMID- 10935680
TI  - Heart failure update.
AB  - The RUSSLAN study, which randomised 504 patients with post-infarction heart
      failure in whom intravenous inotropic support might be deemed appropriate, was
      presented for the first time in a hotline session at the annual meeting of the
      Working Group on Heart Failure of the European Society of Cardiology. The study
      suggested that levosimendan, a new calcium sensitising agent, could be used
      safely in patients with post-infarction heart failure in the absence of severe
      hypotension and that it appeared to improve symptoms and survival. If these
      results can be confirmed it would render it unique among intravenous inotropic
      agents.

PMID- 10935682
TI  - How patients with heart failure are managed in the Czech Republic.

PMID- 10935683
TI  - Inverse correlation of telomerase activity/proliferation of CD4+ T lymphocytes
      and disease progression in simian immunodeficiency virus-infected nonhuman
      primates.
AB  - Both increased lymphocyte renewal with subsequent exhaustion of the immune system
      and impaired T-cell renewal have been put forth to account for CD4+ T-cell
      depletion and development of AIDS in HIV-1-infected humans and SIV-infected
      nonhuman primates. In the present study, telomeric terminal restriction fragment
      length and telomerase activity were used as measures of proliferative activity of
      T lymphocytes from three nonhuman primate species before and after being infected
      with SIV. In peripheral blood T cells, our data show both species and T-cell
      subset-specific differences in proliferative activity accompanied by different
      patterns of disease progression. A significant postinfection increase in
      telomerase/proliferative activity in CD4+ T cells from seropositive sooty
      mangabeys and from normal progressor rhesus macaques was associated with
      asymptomatic infection or delayed disease progression, respectively, whereas a
      decrease in telomerase/proliferative activity detected in CD4+ T cells
      postinfection from SIVsmmPBj14-infected pigtailed macaques was associated with
      rapid CD4+ T-cell depletion and disease progression. The levels of telomerase
      activity observed in CD4+ T cells from peripheral blood closely parallelled those
      seen in CD4+ T cells in lymph node samples from selected animals. Our data
      suggest that an increase in proliferative activity of T lymphocytes in vivo may
      be associated with a favorable course of SIV infection in nonhuman primates.

PMID- 10935684
TI  - Genotoxic and functional consequences of transplacental zidovudine exposure in
      fetal monkey brain mitochondria.
AB  - Mitochondrial toxicity was assessed in the brains of developing Erythrocebus
      patas monkey fetuses exposed in utero to the nucleoside analogue drug zidovudine
      (3'-azido-3'deoxythymidine or AZT). Pregnant E. patas monkeys were given 0 (n =
      5), 10 (n = 3), and 40 (n = 3) mg of AZT/day, equivalent to 21 and 86% of the
      human daily dose, for the last half (about 10 weeks) of gestation. Mitochondria
      were isolated from fetal cerebrum and cerebellum at birth and mitochondrial
      morphology was examined in these tissues by transmission electron microscopy
      (TEM). Oxidative phosphorylation (OXPHOS) enzyme specific activities were
      measured spectrophotometrically. Mitochondrial DNA (mtDNA) integrity and quantity
      were determined by Southern blot and slot blot analysis. In the cerebral
      mitochondria, reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase
      (complex I) specific activity decreased by 25% in monkeys treated with 40 mg of
      AZT/day compared with unexposed monkeys (p > or = .05). At the same AZT dose in
      the cerebral mitochondria, succinate dehydrogenase (complex II) and cytochrome c
      reductase (complex IV)-specific activities showed dose-dependent increases (p >
      or = .05), compared with those in controls. In the cerebellum, no difference was
      seen in mitochondrial OXPHOS enzyme activities between unexposed and exposed
      fetuses. Furthermore, TEM demonstrated no difference in mitochondrial morphology
      in frontal cerebrum or cerebellum from unexposed and exposed fetuses, and all
      fetuses had similar amounts of mtDNA in both tissues. Cerebral mtDNA degradation
      was noted in the highest AZT dosage group, whereas mtDNA from cerebellum was
      uneffected. Thus, in fetal patas monkeys given a human equivalent daily dose of
      AZT during the last half of pregnancy, mitochondria in the fetal cerebrum appear
      to sustain moderate damage, while the fetal cerebellum mitochondria were not
      effected.

PMID- 10935685
TI  - Physician experience in the care of HIV-infected persons is associated with
      earlier adoption of new antiretroviral therapy.
AB  - OBJECTIVE: Recent advances in antiretroviral therapy have led to effective but
      increasingly complex strategies for the treatment of HIV infection. In a previous
      study, we demonstrated that physicians' experience in the care of patients with
      AIDS improves survival. We conducted this study to determine whether greater
      physician experience is associated with earlier adoption and appropriate use of
      new antiretroviral treatment regimens. DESIGN: Retrospective medical record
      review of a population-based sample of HIV-infected individuals who received
      antiretroviral treatment between December 1995 and May 1997 by primary care
      physicians practicing throughout the state of Washington. We classified
      antiretroviral regimens observed into one of four categories based on national
      treatment guidelines. RESULTS: The use of new antiretroviral treatment regimens
      significantly increased during the study period; 22% of patients were treated
      with a protease inhibitor (PI)-based regimen or an alternative PI- or
      nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen between
      December 1995 and November 1996, compared with 57% between April and May 1997 (p
      < .001). After controlling for CD4 count and the calendar period of treatment,
      patients cared for by physicians with greater HIV experience were significantly
      more likely to receive PI-based regimens or alternative PI- or NNRTI-based
      antiretroviral regimens (p = .02). Use of PI-based regimens was also associated
      with lower CD4 count (p < .001) and treatment after January 1997 (p = .02), but
      independent of patient demographic characteristics and the geographic location of
      physicians' practices. CONCLUSIONS: Greater physician experience in the care of
      persons with HIV infection is associated with earlier adoption of new
      antiretroviral treatment regardless of whether physicians practice in a rural or
      urban area.

PMID- 10935686
TI  - Outcome of a second-line protease inhibitor-containing regimen in patients
      failing or intolerant of a first highly active antiretroviral therapy.
AB  - The outcome of second-line protease inhibitor (PI)-containing highly active
      antiretroviral therapy (HAART) was investigated in 263 patients who were failed
      by (n = 148) or intolerant of (n = 115) a first HAART regimen. The endpoints were
      virologic failure (decline in HIV RNA < 1 log10 copies/ml after > or = 2 months)
      and discontinuation due to intolerance/toxicity. During a median follow-up of 483
      days (33-1087 days), 154 patients (59%) discontinued the second regimen, 86 (33%)
      because of intolerance/toxicity; another 135 patients (51.3%) showed virologic
      failure. Independent factors associated with virologic failure (Cox's model) were
      7 to 12 months of first HAART (hazard ratio [HR] 1.70 versus < or = 6 months: 95%
      confidence interval [CI], 1.08-2.70) and gender (HR 1.58 males versus females:
      95% CI, 1.04-2.30); the negatively associated factors were advanced age (HR 0.61
      > 34 years versus < or = 34 years: 95% CI, 0.42-0.88), a saquinavir-containing
      first HAART (HR 0.57 versus indinavir: 95% CI, 0.34-0.93) and change due to
      intolerance/toxicity (HR 0.58 versus failure: 95% CI, 0.35-0.98). The independent
      variables predictive of discontinuation due to intolerance/toxicity were the
      reason for switching (HR 1.79 intolerance versus failure: 95% CI, 1.02-3.16) and
      the first protease inhibitor (PI) regimen (HR 0.42 ritonavir versus indinavir:
      95% CI, 0.22-0.80). Given that patients who are failed by a first regimen are at
      high risk of having rescue therapy fail as well, second-line regimens including
      therapies directed by testing of drug resistance patterns of clinical viral
      isolates are warranted. Patients experiencing toxicity due to a first PI
      containing regimen are at risk of toxicity to other PIs and should be addressed
      to PI-sparing HAART.

PMID- 10935687
TI  - Patient-reported nonadherence to HAART is related to protease inhibitor levels.
AB  - OBJECTIVE: To compare self-reported nonadherence with antiretroviral therapy
      (ART) with predose plasma levels of protease inhibitor (PI). DESIGN: A cross
      sectional study of consecutive patients from a university-based HIV clinic in
      Rome, Italy, was conducted. One hundred and forty HIV-infected patients were
      prescribed regimens containing ritonavir or indinavir. A patient questionnaire
      assessing knowledge of treatment regimen, adherence behavior, reasons for taking
      and missing therapy, factors influencing adherence, and health behaviors was
      administered. A predose PI plasma level was measured concurrently. RESULTS: By
      patient report, 12% missed at least one dose "yesterday," and 24% missed doses in
      the last 3 days; 14% had a predose plasma concentration below the assay limit of
      quantitation (2 ritonavir and 18 indinavir samples). Confusion, poor
      psychological well-being, long office wait, running out of drugs between visits,
      having relatives to remind the patient to take medication, children, and
      alteration of sense of taste were related to unquantifiable predose levels of PI.
      In multivariable analysis, reported nonadherence (odds ratio [OR], 15.8; 95%
      confidence interval [CI], 4.0-63.3) and confusion (OR, 9.9; 95% CI, 1.4-69.6)
      were related to unquantifiable predose levels of PI. CONCLUSION: Self-report of
      missing a dose of antiretroviral medication "yesterday" was related to an
      unmeasurable plasma PI level.

PMID- 10935689
TI  - Relation of lean body mass to health-related quality of life in persons with HIV.
AB  - OBJECTIVE: To determine the nature and strength of the relation between lean body
      mass and measures of health-related quality-of-living (HRQL) including physical
      functioning in men and women with HIV. DESIGN: Cross-sectional analysis using 619
      patients with HIV infection from two cities in the northeastern United States.
      MAIN OUTCOME MEASURES: Lean body mass (LBM) was assessed by bioimpedance analysis
      (BIA). Physical functioning, general health perceptions, energy/fatigue, and
      number of days spent in bed in the last month were determined by patient self
      report. RESULTS: Data from 450 men and 169 women were analyzed. Mean age was 39
      years, 37.6% were nonwhite, and mean CD4 counts were 352 cells/ml. In
      multivariable models, higher LBM was significantly associated with better
      physical functioning in men but not in women. In men, a 10-kg increment in LBM
      was associated with a 3.7 point (95% confidence interval [CI], 0.19-7.2)
      increment in physical functioning (0-100 scale). In similar analyses, higher LBM
      was significantly associated with better general health perceptions (10-kg
      increment in LBM associated with a 4.8 point [95% CI, 1.4-8.1] increment in
      general health perceptions), and fewer days in bed in the last month (10-kg
      increment in LBM associated with 0.9 [95% CI, -1.8-0] fewer days in bed). Lean
      body mass was not independently associated with energy/fatigue. CONCLUSIONS: In
      this diverse population of persons with HIV, LBM was significantly related to
      physical functioning and other measures of HQRL in men, but not in women. In men,
      the relation was linear but relatively weak. These data have potential
      implications for assessing the clinical impact of interventions aimed at
      increasing LBM. Even in men, increases in LBM in the ranges that are currently
      achievable may produce relatively small improvements in physical functioning and
      other measures of HRQL.

PMID- 10935688
TI  - Differential impairment of triazolam and zolpidem clearance by ritonavir.
AB  - BACKGROUND: The viral protease inhibitor ritonavir has the capacity to inhibit
      and induce the activity of cytochrome P450-3A (CYP3A) isoforms, leading to drug
      interactions that may influence the efficacy and toxicity of other antiretroviral
      therapies, as well as pharmacologic treatments of coincident or complicating
      diseases. METHODS: The inhibitory effect of ritonavir on the biotransformation of
      the hypnotic agents triazolam and zolpidem was tested in vitro using human liver
      microsomes. In a double-blind clinical study, volunteer study subjects received
      0.125 mg triazolam or 5.0 mg zolpidem concurrent with low-dose ritonavir (four
      doses of 200 mg), or with placebo. RESULTS: Ritonavir was a potent in vitro
      inhibitor of triazolam hydroxylation but was less potent as an inhibitor of
      zolpidem hydroxylation. In the clinical study, ritonavir reduced triazolam
      clearance to < 4% of control values (p < .005), prolonged elimination half-life
      (41 versus 3 hours; p < .005), and magnified benzodiazepine agonist effects such
      as sedation and performance impairment. In contrast, ritonavir reduced zolpidem
      clearance to 78% of control values (p < .08), and slightly prolonged elimination
      half-life (2.4 versus 2.0 hours; NS). Benzodiazepine agonist effects of zolpidem
      were not altered by ritonavir. CONCLUSION: Short-term low-dose administration of
      ritonavir produces a large and significant impairment of triazolam clearance and
      enhancement of clinical effects. In contrast, ritonavir produced small and
      clinically unimportant reductions in zolpidem clearance. The findings are
      consistent with the complete dependence of triazolam clearance on CYP3A activity,
      compared with the partial dependence of zolpidem clearance on CYP3A.

PMID- 10935690
TI  - Protection of cynomolgus macaque against cervicovaginal transmission of SIVmac251
      by the spermicide benzalkonium chloride.
AB  - We evaluated the potential effectiveness of a spermicide cationic surfactant,
      benzalkonium chloride (BZK), to prevent the transmission of simian
      immunodeficiency virus (SIV) after intravaginal inoculation in 12 cynomolgus
      macaques. The inoculation procedure involved deposition of 6.7 ivag-AID50 of cell
      free SIVmac251 into the receiving vagina, four times over a 2-week period, at the
      end of the luteal phase of the menstrual cycle. Six randomly selected females
      received vaginally foam containing BZK (7.37%, wt/wt) before each inoculation
      (BZK group), whereas the remaining were not pretreated (control group). In
      controls, 5 animals presented persistent SIV infection and 1 had a transient
      viremia. The number of uninfected animals was higher in the BZK group (6 of 6)
      than in controls (0 of 6). These findings demonstrate that BZK placed in the
      vaginal receptacle prior to SIV inoculation provides a significant protection in
      vivo. The wide spectrum of antimicrobial activities of BZK (including HIV) in
      addition to its efficiency to block the transmucosal passage of SIV in the
      macaque model qualifies this drug as an attractive topical microbicide to prevent
      sexually transmitted infections in humans.

PMID- 10935691
TI  - Effect of prenatal zidovudine on disease progression in perinatally HIV-1
      infected infants.
AB  - OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on
      the course of HIV- 1 infection in children by comparing the clinical outcome of
      infants born to HIV- 1-seropositive mothers who did versus those who did not
      receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive
      mothers and their infants were reviewed retrospectively. Participants were
      divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main
      outcome measure was rapid disease progression (RPD) in the infant, defined as
      occurrence of a category C disease or AIDS-related death before 18 months of age.
      RESULTS: HIV vertical transmission rates were significantly different (no ZDV
      versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate
      was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012),
      and prematurity was significantly associated with a higher risk of RPD (p =
      .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally
      infected infants born to HIV-infected mothers treated with ZDV than among
      infected infants born to untreated mothers. The decreased proportion of infected
      infants with nonrapid disease progression in the former group might be related to
      the ability of ZDV to block intrapartum transmission preferentially and also to
      nonrapid disease progression resulting from intrapartum transmission.

PMID- 10935692
TI  - Sex- and drug-related risk among populations of younger and older injection drug
      users in adjacent neighborhoods in San Francisco.
AB  - The objective of this study was to compare drug injection- and sex-related risk
      behaviors of younger and older injection drug users (IDUs) in two adjacent
      neighborhoods. IDUs were recruited from street settings in two adjacent
      neighborhoods in San Francisco in April, 1997. All participants were interviewed
      using a standardized questionnaire and were tested for HIV antibodies. Drug
      injection- and sex-related risk behaviors were compared between younger IDUs (<
      30 years; n = 56) and older IDUs (> or = 30 years; n = 116). Younger IDUs were
      more likely to be white, be homeless, have injected amphetamines, and have been
      arrested in the past year. Older IDUs were more likely to be African American and
      smoke crack cocaine; they had injected a mean of 18 years longer. Younger IDUs
      were more likely to have shared syringes in the past month (52% versus 10%; p <
      .05), report drug overdose in the past 15 months (39% versus 7%; p < .05), and to
      have had unprotected vaginal intercourse in the past 6 months (77% versus 53%; p
      < .05). After controlling for confounding factors using logistic regression
      analysis, all these associations remained significant. There is an urgent need
      for innovative prevention programs that target younger, homeless IDUs.

PMID- 10935693
TI  - Very young gay and bisexual men are at risk for HIV infection: the San Francisco
      Bay Area Young Men's Survey II.
AB  - OBJECTIVES: To compare HIV seroprevalence and sexual risk behavior among very
      young gay and bisexual men (aged 15-17 years) and their older counterparts (aged
      18-22 years). To examine drug-use patterns and correlates of sexual risk behavior
      in both of these age groups. DESIGN AND METHODS: An interviewer-administered
      cross-sectional survey of 719 gay and bisexual males between 15 and 22 years old
      was conducted through a venue-based sampling design. Blood specimens were
      collected and tested for HIV antibodies, hepatitis B, and syphilis. Interviews
      assessed sexual and drug-use behavior as well as psychosocial variables believed
      to be related to sexual risk-taking, including self-acceptance of gay or bisexual
      identity, perceptions of peer norms concerning safer sex, and perceptions of the
      ability to practice safer sex (safer sex self-efficacy). RESULTS: Of the 719
      participants, 100 (16.2%) were aged between 15 and 17 years. HIV seroprevalence
      was somewhat lower among those aged 15 to 17 years (2.0%) compared with those
      aged 18 to 22 years (6.8%). Overall, the prevalence of hepatitis-B core antibody
      was significantly lower in the younger age group (5.0%) than in the older group
      (14.1%). The men aged 15 to 17 years used alcohol, ecstasy, and heroin less
      frequently than those aged 18 to 22 years. The age groups did not differ in the
      proportion of men who reported any unprotected anal intercourse in the previous 6
      months (31.2%). In both age groups, use of amphetamines, ecstasy, and amyl
      nitrate was associated with unprotected anal intercourse. Self-acceptance of gay
      or bisexual identity was related to less sexual risk for those aged 15 to 17
      years. In both age groups, greater safer sex self-efficacy was linked to less HIV
      sexual risk-taking. In the younger group, perceptions of peer norms that support
      safer sex were related to less risk behavior. CONCLUSIONS: Very young gay and
      bisexual men engage in unprotected anal sex at rates comparable with those for
      their somewhat older counterparts, raising serious concern over their risk of
      acquiring HIV infection. To prevent seroconversions, interventions must target
      those <18 years of age, and prevention programs should address the use of certain
      drugs in relation to sex and sexual risk-taking. To be most effective, programs
      should develop innovative communication strategies to take into account lack of
      self-acceptance of gay or bisexual identity and low self-efficacy for practicing
      safer sex.

PMID- 10935694
TI  - Identification of a high-risk heterosexual population for HIV prevention trials
      in Rio de Janeiro, Brazil. Projeto Praco Onze Study Group.
AB  - The study of interventions to prevent HIV transmission requires access to
      populations with a high rate of HIV transmission. We estimated HIV incidence
      among heterosexual males and females who were seen at an HIV testing site in Rio
      de Janeiro, Brazil. Stored sera from individuals who visited the site between
      March and December 1998 were analyzed using the sensitive/less sensitive (S/LS)
      assay and a chart abstraction was performed. During the study period, 6353 serum
      samples were tested. Of those tested, 1203 were found to be HIV-seropositive or
      indeterminate, of which 1050 (87%) remained available for further testing. In
      addition, 84 serum samples, representing 63 adults, were found to produce results
      suggesting early HIV infection. Of these, 14 were heterosexual and female (median
      age, 38 years), and 19 were heterosexual and male (median age, 25 years). The
      estimated HIV seroincidence was 1.9 (95% confidence limits (CL), 0.9%-3.9%) and
      2.8 (95% CL, 1.4%-5.3%) per 100 person-years among heterosexual women and men,
      respectively. A survey on willingness to participate in future placebo-controlled
      HIV vaccine trials in this population indicated that 54.5% and 53.9% of
      heterosexual women and men, respectively, indicated that they would definitely be
      willing to participate. We have identified a heterosexual population in Rio de
      Janeiro with a high rate of HIV transmission willing to participate in placebo
      controlled vaccine trials. This study demonstrates the usefulness of the newly
      described S/LS assay, which allows one to estimate HIV incidence from single
      serum specimens.

PMID- 10935696
TI  - Estimating the national cost of treating people with HIV disease: patient, payer,
      and provider data.
AB  - OBJECTIVE: Existing estimates of the national cost of treating all people with
      HIV disease use data from a sample of people with HIV disease to extrapolate the
      cost of treating all people with HIV disease (patient-based approach). This study
      derives estimates using two novel approaches (i.e., payer-based and provider
      based) and compares these with existing estimates. DATA SOURCES: These include
      the Health Insurance Association of American and the American Council of Life
      Insurance 1996 HIV survey, the 1996 State Inpatient Databases (SID) maintained by
      the Agency for Healthcare Research and Quality, and the IMS America Ltd. survey
      of independent and chain drugstores. PRINCIPAL FINDINGS: The cost of treating all
      people with HIV disease in 1996 was between $6.7 and $7.8 billion U.S., and the
      average annual cost of treating a person with HIV disease was between $20,000 and
      $24,700 U.S. CONCLUSIONS: Analysts should derive estimates of the cost of
      treating people with HIV disease using several different approaches. K

PMID- 10935695
TI  - HIV/AIDS epidemic in French Guiana: 1979-1997. Groupe d'Etude Clinique de
      l'Infection VIH en Guyane Francaise.
AB  - The incidence of AIDS in French Guiana remains one of the highest in Latin
      America and the Caribbean. The annual AIDS incidence rate increased continually
      from the start of the epidemic until 1995, when it reached 59.3/100,000
      population declining thereafter to 26.6 in 1997. The prevalence of HIV in
      pregnant women was 0.9% in 1993, increasing to 1.3% in 1995, and that in
      individuals attending sexually transmitted disease (STD) clinics was 2.1% in
      1996. We included 224 patients in a study of survival after AIDS diagnosis. The
      principal AIDS-defining diagnosis was tuberculosis in 20.5% of reported cases.
      The median duration of survival was 10.2 months. Multivariate analysis showed
      that, patients > or = 45 years at entry progressed more rapidly to AIDS than
      younger patients. HIV prevention and access to health care should be developed in
      the various ethnic communities and adapted to cultural status. The progressive
      implementation of multiple antiretroviral therapies since 1996 may further reduce
      progression of the disease but early HIV diagnosis is required to improve the
      overall prognosis of HIV-infected patients.

PMID- 10935697
TI  - In vivo fluctuation of HTLV-I and HTLV-II proviral load in patients receiving
      antiretroviral drugs.
AB  - HTLV-I and HTLV-II infect T lymphocytes. A high HTLV-I proviral load in
      peripheral blood mononuclear cells (PBMCs) has been associated with a higher risk
      of neurologic disease. For HTLV-II, large numbers of infected lymphocytes might
      contribute to accelerate the immunodeficiency and increase the risk of neuropathy
      in HTLV-II/HIV-1 coinfected people. We have examined the impact of antiretroviral
      drugs on HTLV proviral load, testing longitudinal samples collected from 1 HTLV-I
      infected patient suffering HTLV-I-associated myelopathy (HAM), and two HTLV-II/
      HIV-1 coinfected subjects. The HAM patient showed a reduction greater than 2 log
      in the peripheral proviral load after being treated with zidovudine and
      lamivudine. In contrast, potent antiretroviral treatment in HIV-1/HTLV-II
      coinfected carriers produced an initial increase in the HTLV proviral load, which
      was followed by a reduction greater than 1 log thereafter. In conclusion,
      antiretroviral drugs seem to reduce HTLV proviral load, although in HIV-1
      coinfected persons a transient increase in HTLV proviral load could reflect the
      rapid blocking of HIV-1 replication occurring in response to therapy, thus
      causing an increase in the number of circulating T lymphocytes carrying HTLV
      proviral DNA.

PMID- 10935698
TI  - Salvage therapy and formulation of highly active antiretroviral therapy.

PMID- 10935699
TI  - Endothelin-1, endothelin-3 and their receptors (endothelin(A) and endothelin(B))
      in chronic renal transplant rejection in rats.
AB  - Endothelins (ET) are a family of vasoactive peptides that play an important role
      in several disorders affecting kidneys. In this study we investigated the
      expressions of ET-1, ET-3, and their receptors, ET(A) and ET(B), in a rat chronic
      renal transplant rejection model. Renal allografts were performed (F344 -->
      Lewis) with bilateral nephrectomy in recipients. For isograft control, lewis -->
      lewis transplantations were performed. All recipients were sacrificed 140 days
      after transplantation and the grafts were analyzed histologically. ET-1 and ET-3
      protein expression in grafts was measured by immunohistochemistry and ELISA.
      Semiquantitative RT-PCR methods were used for mRNA levels of ET-1, ET-3, ET(A)
      and ET(B). No evidence of chronical rejection was manifested in isografts. The
      allografted rats showed proteinuria and increased serum creatinine levels.
      Histologically, renal allografts showed atrophy and sclerosis of the glomeruli,
      cortical scarring and vascular intimal thickening. Immunohistochemically, ET-1
      and ET-3 were localized in the convoluted tubules, collecting ducts, endothelium
      and smooth muscle cells of the large blood vessels. Significantly increased
      staining for ET-1 and ET-3 were found in allografts compared to isografts.
      Simultaneously, ELISA for ET-1 and ET-3 showed elevated protein concentrations in
      allografts compared to isografts. Allografts showed significantly increased ET-1-
      and ET-3 mRNA compared to isografts. On the other hand, a significant down
      regulation of the ET(A) mRNA was noted, and the ET(B) mRNA remained unchanged.
      The data from the present study suggest that alteration of ET system may be of
      importance in the pathogenesis of chronic renal transplant rejection.

PMID- 10935700
TI  - An unusual presentation of invasive aspergillosis after lung transplantation.
AB  - Aspergillus infections in lung transplant patients are frequently reported with a
      large pattern of manifestations varying from simple colonization of the lungs to
      complicated infections. Pulmonary invasive aspergillosis and disseminated
      aspergillosis often result in death. The majority of cases occur during the first
      months after transplantation with pulmonary involvement and have been described
      as the first clinical localization of the disease. Here we present the first
      reported case of an endophthalmitis caused by Aspergillus fumigatus developing 18
      months after lung transplantation, and presenting as a manifestation of invasive
      aspergillosis.

PMID- 10935701
TI  - Long-term evaluation of proliferative donor antigen-specific reactivity in
      cadaveric kidney transplant recipients.
AB  - Development of donor-specific proliferative hyporeactivity has been evaluated in
      many studies for its usefulness in identifying transplant recipients at low risk
      of immunological complications. These studies often result in controversial
      conclusions, however. The authors claim that the discrepancy in the predictive
      value of mixed lymphocyte culture- (MLC) reactivity might partly be due to
      differences in presentation and interpretation of results. The purpose of this
      study is to investigate the usefulness of a normalized evaluation of antigen
      specific donor-reactivity in a small number of kidney transplant recipients. This
      could then serve as a basis for an extended clinical study. Ten cadaveric kidney
      recipients were tested for proliferative reactivity to donor- and third-party
      antigens up to 20 months posttransplantation. Expressing donor-specific
      reactivity as a relation between the percentage of pretransplant responses
      towards donor splenocytes and the percentage of pretransplant responses towards
      third-party donor cells should minimize influences of e. g. uremia, current
      immunosuppression or infections on the evaluation of specific reactivity and thus
      should allow an evaluation of the donor-specificity of T-cell alloresponses
      independently of fluctuations in global responsiveness. Four of ten recipients
      acquired a state of donor-specific hyporeactivity ( < 75 % relative specific
      reactivity) at 20 months post-transplantation (61 +/- 12%, mean +/- SD). Six
      patients were classified non-hyporeactive (98 +/- 10% mean relative specific
      reactivity). Relative specific reactivity did not correlate with the levels of
      general reactivity. Three of the four hyporeactive and four of the six non
      hyporeactive patients developed acute rejection. Stable graft function at 20
      months posttransplantation (serum creatinine < or = 2 mg/dl) was not closely
      related to the reactivity status, as five of eight patients with well-functioning
      grafts did not develop relative specific hyporeactivity. One recipient with
      chronic rejection was classified hyporeactive. One non-hyporeactive patient lost
      his graft due to non-immunological causes. Our data suggest that post-transplant
      relative specific reactivity does not predict acute rejection. Downregulation of
      donor-specific reactivity might not be a prerequisite for stable graft function
      but could help identifying recipients who require less immunosuppression. This,
      however, remains to be established in a prospective immunosuppression-weaning
      study.

PMID- 10935702
TI  - Long-term role of nitric oxide in the enteric nervous system of the transplanted
      rat intestine.
AB  - We investigated the long-term changes of the nitric oxide (NO)-related neural
      component after syngeneic total small bowel transplantation in rats. In the
      present study, the NO-related neural component was examined using the
      electrophysiological and NADPH-diaphorase histochemical technique. The rats were
      divided into four groups: an untreated young adult control group, an untreated 2
      year-old control group, a group killed 1 month after transplantation, and a group
      killed 2 years after transplantation. A superfusion apparatus was used to
      evaluate the response of jejunal strips to electrical transmural stimulation. In
      the presence of adrenergic and cholinergic blockade, the inhibitory effect of L
      N(G)-nitro arginine (L-NNA; a nitric oxide synthesis inhibitor) on nonadrenergic,
      noncholinergic (NANC) relaxation was expressed as a L-NNA-sensitive component.
      The L-NNA-sensitive component accounted for 41.6 +/- 4.6% (mean +/- SE), 43.1 +/-
      3.5%,54.6 +/- 4.1%, and 55.8 +/- 3.5% in the young control group, 2-year control
      group, 1-month transplant group, and 2-year transplant group, respectively, being
      significantly higher in the transplant groups (p < 0.05). The actual strength of
      the L-NNA-sensitive component was 0.24 +/- 0.03 (mean +/- SE), 0.26 +/- 0.02,
      0.44 +/- 0.04, and 0.46 +/- 0.04 mg of tension per mg of wet weight,
      respectively, also being significantly higher in the transplant groups (p <
      0.001). In addition, the percentage of NADPH-diaphorase-positive fibers was 24.1
      +/- 1.1% (mean +/- SE), 25.5 +/- 1.4%, 31.0 +/- 1.6%, and 30.9 +/- 2.0%,
      respectively, being significantly higher in the transplant groups (p < 0.05).
      These results suggest that NO neurons in the intrinsic jejunal nervous system
      have an adaptive role in maintaining intestinal graft motility.

PMID- 10935703
TI  - Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients
      with chronical cyclosporine nephrotoxicity.
AB  - Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however,
      after years, renal function deteriorates, possibly due to chronic toxicity.
      Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic
      immunosuppressant that might be effective in chronical transplant arteriolopathy.
      We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal
      transplant recipients (10.8 +/- 3.9 (SD) years of age at transplantation, 11/18
      with a history of rejections) with biopsy-proven chronic arteriolopathy and other
      signs of CyA toxicity at a mean follow up time of 6.2 +/- 2.7 (range 2.3-11.8)
      years after transplantation. One month prior to conversion, mean serum creatinine
      was 171 +/- 96 micromol/l, lower than at the time of conversion (188 +/- 100
      micromol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months,
      range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased
      significantly to 127 +/- 69 micromol/l (P = 0,0003, paired t-test). The CyA
      dosage was reduced from a mean of 150 +/- 39 mg/ m2 per day to 59 +/- 13 mg/m2
      per day in 7 patients, and CyA was discontinued in 11 patients after a median
      period of nine months (range 1-18 months). After a median period of 21 days, a
      pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117
      +/- 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid
      (MPA) trough concentration was 4.0 +/- 2.0 microg/ml, range 1.4-7.9 microg/ml.
      Mean 12 h MPA AUC was 70.6 +/- 28.1 (range 31.9-127) microg x h/ml. Except for
      one patient with diarrhea associated with a high AUC, and for one patient with a
      steroid-sensitive rejection episode after 566 days, no other patient experienced
      side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2
      per day. We conclude that MMF allows safe reduction of CyA with markedly better
      graft function, suggesting that chronical CyA-toxicity partially accounts for
      deteriorating allograft function.

PMID- 10935704
TI  - Liver transplantation for alpha-1-antitrypsin deficiency in children.
AB  - Alpha-1-antitrypsin (a1-AT) deficiency is an inborn error of metabolism, which
      can cause liver disease. The condition is one of the most common genetic
      disorders in the Caucasian population. Here we review our experience with 21
      children suffering from end-stage liver disease due to a1-AT deficiency. All
      children are PIZZ homozygotes. Nineteen of them initially presented with neonatal
      jaundice and two with hepatosplenomegaly in childhood. Twenty-five liver
      transplantations were performed. All children are currently alive at a median
      followup of 40 months. Liver replacement provides the only definite treatment for
      children with end-stage liver disease associated with a1-AT deficiency. Excellent
      results can be achieved by reducing waiting time for transplantation and by early
      referral to a liver transplant centre.

PMID- 10935705
TI  - Effect of anti-CD4 monoclonal antibody administration on rat small bowel
      allograft survival and circulating leukocyte populations.
AB  - This study assessed the effect of an anti-rat CD4 monoclonal antibody (OX38) on
      heterotopic small bowel allograft rejection. Fully allogeneic small bowel
      transplants were performed in the PVG-to-DA-rat strain combination. Animals
      received either i) short course (days -1, 0 and 1) of 1 mg/kg per day OX38, ii)
      short course of 5 mg/kg per day or iii) extended course (days -2, -1, 0, 1, 2 and
      twice weekly thereafter) of 1 mg/kg per day. Both the high dose (13 days) and
      extended low-dose (12 days) courses prolonged graft survival compared to
      untreated control animals (7 days). The low-dose, short-course treatment had no
      effect. Similar regimens were given to animals that did not receive transplants
      and in which peripheral blood CD4+ cell counts fell to between 20 and 55 % of
      pretreatment levels and 20-30% of binding sites were blocked. In summary, anti
      CD4 monoclonal antibody therapy delayed rejection of rat small bowel allografts;
      however, long-term survival was not achieved.

PMID- 10935706
TI  - Obliterative airway disease in a porcine heterotopic bronchial allograft model.
AB  - Representative animal models are needed for the study of posttransplant
      obliterative bronchiolitis (OB). Because human OB originates in terminal bronchi,
      the validity of tracheal models can be questioned. Using our hetrotopic model, we
      implanted pieces of a lobar bronchus subcutaneously into domestic pigs. Five
      groups were included: autograft implants, allograft implants, allograft implants
      with 2 regimens of cyclosporine (CsA)azathioprine (AZA)-methylprednisolone (MP),
      and allograft implants with CsA-SDZ RAD-MP. Samples were harvested at 2 weeks and
      at 1, 2, and 3 months. The histological findings were graded from 0 to 3.
      Following initial ischemic epithelial damage, autograft implants recovered, but
      untreated allografts and those treated with CsA-AZA-MP were totally and
      permanently damaged within one month. In the group treated with CsA-SDZ RAD-MP, a
      maximal grade 1.5 +/- 0.5 epithelial injury was seen at one month. Epithelial
      damage preceded and correlated with luminal obliteration. The obliterative
      lesions histologically resembled human OB. Differences from our previous findings
      with terminal bronchioles were minor. This study supports the use of larger-size
      airways in the study of OB.

PMID- 10935707
TI  - Heparin and phentolamine combined, rather than heparin alone, improves hepatic
      microvascular procurement in a non-heart-beating donor rat-model.
AB  - Improvement of organ procurement from non-heart-beating donors (NHBDs) could
      increase the donor organ pool for liver transplantation. Whether anti-coagulative
      and anti-vasospastic substances can improve hepatic microvascular preservation
      from NHBDs is unknown. In donor rats which were pretreated with either heparin (n
      = 6) or heparin combined with phentolamine (n = 7) 10 min prior to cardiac
      arrest, the extent and homogeneity of hepatic microvascular reperfusion was
      assessed at the end of a 60-min period of cardiac arrest using in situ
      fluorescence microscopy. Non-pretreated animals with cardiac arrest for 60 min
      served as controls (n = 6). In the non-treated NHBDs, arterial gravity perfusion
      of 100 cm H2O with HTK-solution led to a hepatic acinar reperfusion of only
      approximately 22 % with a remarkably diminished sinusoidal density. Application
      of heparin prior to cardiac arrest resulted in a two-fold, but insignificant
      increase of acinar perfusion and sinusoidal density with a still considerable
      heterogeneity of both parameters. Livers of NHBDs that additionally received
      phentolamine exhibited significantly increased values of both acinar perfusion
      and sinusoidal density. Phentolamine was found to reduce heterogeneity of organ
      microperfusion. Thus, our results indicate that the combined application of
      heparin and phentolamine is a useful additive for optimizing the quality of
      organs harvested from NHBDs.

PMID- 10935708
TI  - High security standards in organ donation and transplantation ISO 9001
      certificate for organ procurement organisation in Germany.

PMID- 10935709
TI  - A single case of orthotopic liver transplantation with a graft from a donor with
      tetanus.

PMID- 10935710
TI  - The alkaloid sinomenine lacks efficacy in rat heart transplantation.

PMID- 10935711
TI  - Separating style and content with bilinear models.
AB  - Perceptual systems routinely separate "content" from "style," classifying
      familiar words spoken in an unfamiliar accent, identifying a font or handwriting
      style across letters, or recognizing a familiar face or object seen under
      unfamiliar viewing conditions. Yet a general and tractable computational model of
      this ability to untangle the underlying factors of perceptual observations
      remains elusive (Hofstadter, 1985). Existing factor models (Mardia, Kent, &
      Bibby, 1979; Hinton & Zemel, 1994; Ghahramani, 1995; Bell & Sejnowski, 1995;
      Hinton, Dayan, Frey, & Neal, 1995; Dayan, Hinton, Neal, & Zemel, 1995; Hinton &
      Ghahramani, 1997) are either insufficiently rich to capture the complex
      interactions of perceptually meaningful factors such as phoneme and speaker
      accent or letter and font, or do not allow efficient learning algorithms. We
      present a general framework for learning to solve two-factor tasks using bilinear
      models, which provide sufficiently expressive representations of factor
      interactions but can nonetheless be fit to data using efficient algorithms based
      on the singular value decomposition and expectation-maximization. We report
      promising results on three different tasks in three different perceptual domains:
      spoken vowel classification with a benchmark multi-speaker database,
      extrapolation of fonts to unseen letters, and translation of faces to novel
      illuminants.

PMID- 10935712
TI  - Relationships between the A priori and A posteriori errors in nonlinear adaptive
      neural filters.
AB  - The lower bounds for the a posteriori prediction error of a nonlinear predictor
      realized as a neural network are provided. These are obtained for a priori
      adaptation and a posteriori error networks with sigmoid nonlinearities trained by
      gradient-descent learning algorithms. A contractivity condition is imposed on a
      nonlinear activation function of a neuron so that the a posteriori prediction
      error is smaller in magnitude than the corresponding a priori one. Furthermore,
      an upper bound is imposed on the learning rate eta so that the approach is
      feasible. The analysis is undertaken for both feedforward and recurrent nonlinear
      predictors realized as neural networks.

PMID- 10935713
TI  - The VC dimension for mixtures of binary classifiers.
AB  - The mixtures-of-experts (ME) methodology provides a tool of classification when
      experts of logistic regression models or Bernoulli models are mixed according to
      a set of local weights. We show that the Vapnik-Chervonenkis dimension of the ME
      architecture is bounded below by the number of experts m and above by O(m4s2),
      where s is the dimension of the input. For mixtures of Bernoulli experts with a
      scalar input, we show that the lower bound m is attained, in which case we obtain
      the exact result that the VC dimension is equal to the number of experts.

PMID- 10935714
TI  - The early restart algorithm.
AB  - Consider an algorithm whose time to convergence is unknown (because of some
      random element in the algorithm, such as a random initial weight choice for
      neural network training). Consider the following strategy. Run the algorithm for
      a specific time T. If it has not converged by time T, cut the run short and rerun
      it from the start (repeat the same strategy for every run). This so-called
      restart mechanism has been proposed by Fahlman (1988) in the context of
      backpropagation training. It is advantageous in problems that are prone to local
      minima or when there is a large variability in convergence time from run to run,
      and may lead to a speed-up in such cases. In this article, we analyze
      theoretically the restart mechanism, and obtain conditions on the probability
      density of the convergence time for which restart will improve the expected
      convergence time. We also derive the optimal restart time. We apply the derived
      formulas to several cases, including steepest-descent algorithms.

PMID- 10935715
TI  - Attractor dynamics in feedforward neural networks.
AB  - We study the probabilistic generative models parameterized by feedforward neural
      networks. An attractor dynamics for probabilistic inference in these models is
      derived from a mean field approximation for large, layered sigmoidal networks.
      Fixed points of the dynamics correspond to solutions of the mean field equations,
      which relate the statistics of each unit to those of its Markov blanket. We
      establish global convergence of the dynamics by providing a Lyapunov function and
      show that the dynamics generate the signals required for unsupervised learning.
      Our results for feedforward networks provide a counterpart to those of Cohen
      Grossberg and Hopfield for symmetric networks.

PMID- 10935716
TI  - Visualizing the function computed by a feedforward neural network.
AB  - A method for visualizing the function computed by a feedforward neural network is
      presented. It is most suitable for models with continuous inputs and a small
      number of outputs, where the output function is reasonably smooth, as in
      regression and probabilistic classification tasks. The visualization makes
      readily apparent the effects of each input and the way in which the functions
      deviate from a linear function. The visualization can also assist in identifying
      interactions in the fitted model. The method uses only the input-output
      relationship and thus can be applied to any predictive statistical model,
      including bagged and committee models, which are otherwise difficult to
      interpret. The visualization method is demonstrated on a neural network model of
      how the risk of lung cancer is affected by smoking and drinking.

PMID- 10935717
TI  - Discriminant pattern recognition using transformation-invariant neurons.
AB  - To overcome the problem of invariant pattern recognition, Simard, LeCun, and
      Denker (1993) proposed a successful nearest-neighbor approach based on tangent
      distance, attaining state-of-the-art accuracy. Since this approach needs great
      computational and memory effort, Hastie, Simard, and Sackinger (1995) proposed an
      algorithm (HSS) based on singular value decomposition (SVD), for the generation
      of nondiscriminant tangent models. In this article we propose a different
      approach, based on a gradient-descent constructive algorithm, called TD-Neuron,
      that develops discriminant models. We present as well comparative results of our
      constructive algorithm versus HSS and learning vector quantization (LVQ)
      algorithms. Specifically, we tested the HSS algorithm using both the original
      version based on the two-sided tangent distance and a new version based on the
      one-sided tangent distance. Empirical results over the NIST-3 database show that
      the TD-Neuron is superior to both SVD- and LVQ-based algorithms, since it reaches
      a better trade-off between error and rejection.

PMID- 10935718
TI  - Observable operator models for discrete stochastic time series.
AB  - A widely used class of models for stochastic systems is hidden Markov models.
      Systems that can be modeled by hidden Markov models are a proper subclass of
      linearly dependent processes, a class of stochastic systems known from
      mathematical investigations carried out over the past four decades. This article
      provides a novel, simple characterization of linearly dependent processes, called
      observable operator models. The mathematical properties of observable operator
      models lead to a constructive learning algorithm for the identification of
      linearly dependent processes. The core of the algorithm has a time complexity of
      O(N + nm3), where N is the size of training data, n is the number of
      distinguishable outcomes of observations, and m is model state-space dimension.

PMID- 10935719
TI  - Adaptive method of realizing natural gradient learning for multilayer
      perceptrons.
AB  - The natural gradient learning method is known to have ideal performances for on
      line training of multilayer perceptrons. It avoids plateaus, which give rise to
      slow convergence of the backpropagation method. It is Fisher efficient, whereas
      the conventional method is not. However, for implementing the method, it is
      necessary to calculate the Fisher information matrix and its inverse, which is
      practically very difficult. This article proposes an adaptive method of directly
      obtaining the inverse of the Fisher information matrix. It generalizes the
      adaptive Gauss-Newton algorithms and provides a solid theoretical justification
      of them. Simulations show that the proposed adaptive method works very well for
      realizing natural gradient learning.

PMID- 10935720
TI  - Nonmonotonic generalization bias of Gaussian mixture models.
AB  - Theories of learning and generalization hold that the generalization bias,
      defined as the difference between the training error and the generalization
      error, increases on average with the number of adaptive parameters. This article,
      however, shows that this general tendency is violated for a gaussian mixture
      model. For temperatures just below the first symmetry breaking point, the
      effective number of adaptive parameters increases and the generalization bias
      decreases. We compute the dependence of the neural information criterion on
      temperature around the symmetry breaking. Our results are confirmed by numerical
      cross-validation experiments.

PMID- 10935721
TI  - Efficient block training of multilayer perceptrons.
AB  - The attractive possibility of applying layerwise block training algorithms to
      multilayer perceptrons MLP, which offers initial advantages in computational
      effort, is refined in this article by means of introducing a sensitivity
      correction factor in the formulation. This results in a clear performance
      advantage, which we verify in several applications. The reasons for this
      advantage are discussed and related to implicit relations with second-order
      techniques, natural gradient formulations through Fisher's information matrix,
      and sample selection. Extensions to recurrent networks and other research lines
      are suggested at the close of the article.

PMID- 10935722
TI  - An optimization approach to design of generalized BSB neural associative
      memories.
AB  - This article is concerned with the synthesis of the optimally performing GBSB
      (generalized brain-state-in-a-box) neural associative memory given a set of
      desired binary patterns to be stored as asymptotically stable equilibrium points.
      Based on some known qualitative properties and newly observed fundamental
      properties of the GBSB model, the synthesis problem is formulated as a
      constrained optimization problem. Next, we convert this problem into a quasi
      convex optimization problem called GEVP (generalized eigenvalue problem). This
      conversion is particularly useful in practice, because GEVPs can be efficiently
      solved by recently developed interior point methods. Design examples are given to
      illustrate the proposed approach and to compare with existing synthesis methods.

PMID- 10935723
TI  - Nonholonomic orthogonal learning algorithms for blind source separation.
AB  - Independent component analysis or blind source separation extracts independent
      signals from their linear mixtures without assuming prior knowledge of their
      mixing coefficients. It is known that the independent signals in the observed
      mixtures can be successfully extracted except for their order and scales. In
      order to resolve the indeterminacy of scales, most learning algorithms impose
      some constraints on the magnitudes of the recovered signals. However, when the
      source signals are nonstationary and their average magnitudes change rapidly, the
      constraints force a rapid change in the magnitude of the separating matrix. This
      is the case with most applications (e.g., speech sounds, electroencephalogram
      signals). It is known that this causes numerical instability in some cases. In
      order to resolve this difficulty, this article introduces new nonholonomic
      constraints in the learning algorithm. This is motivated by the geometrical
      consideration that the directions of change in the separating matrix should be
      orthogonal to the equivalence class of separating matrices due to the scaling
      indeterminacy. These constraints are proved to be nonholonomic, so that the
      proposed algorithm is able to adapt to rapid or intermittent changes in the
      magnitudes of the source signals. The proposed algorithm works well even when the
      number of the sources is overestimated, whereas the existent algorithms do not
      (assuming the sensor noise is negligibly small), because they amplify the null
      components not included in the sources. Computer simulations confirm this
      desirable property.

PMID- 10935724
TI  - Parameters affecting gene expression from the Pm promoter in gram-negative
      bacteria.
AB  - The Pm promoter inserted chromosomally or in broad-host-range replicons based on
      plasmid RSF1010 or RK2 are useful systems for both high- and low-level expression
      of cloned genes in several gram-negative bacterial species. The positive Pm
      regulator XylS is activated by certain substituted benzoic acid derivatives, and
      here we show that these effectors induce expression of Pm at similar relative
      ranking levels in both Escherichia coli and Pseudomonas aeruginosa However, the
      kinetics of expression was not the same in the two organisms. Different carbon
      sources and dissolved oxygen levels displayed limited effects on expression, but
      surprisingly the pH of the growth medium was found to be of major importance. By
      combining the effects of genetic and environmental parameters, expression from Pm
      could be varied over a ten-thousand- to a hundred-thousand-fold continuous range,
      and as an example of its applications we showed that Pm can be used to control
      the xanthan biosynthesis in Xanthomonas campestris.

PMID- 10935725
TI  - Pm promoter expression mutants and their use in broad-host-range RK2 plasmid
      vectors.
AB  - By coupling the Pm/xylS promoter system to minimal replicons of the broad-host
      range plasmid RK2 we recently showed that such vectors are useful for both high-
      and low-level inducible expression of cloned genes in gram-negative bacteria. In
      this report, we extend this potential by identifying point mutations in or near
      the -10 transcriptional region of Pm. Point mutations leading to gene-independent
      enhancements of expression levels of the induced state or reduced background
      expression levels were identified using Escherichia coli as a host. By combining
      these mutations an additive effect in expression levels from the constructed Pm
      was observed. The highest induced expression level was obtained by inserting an
      E. coli consensus sigma70 - 10 recognition region. Most of the remaining
      activities in the reduced-background mutations appeared to originate from a
      transcriptional start site other than Pm. The effects of some of these mutations
      were also analyzed in Pseudomonas aeruginosa and were found to act similarly, but
      less pronounced in this host.

PMID- 10935726
TI  - In vitro determined kinetic properties of mutant phosphoglucomutases and their
      effects on sugar catabolism in Escherichia coli.
AB  - Based on primary amino acid sequence comparisons with other phosphoglucomutases,
      12 conserved residues in the Acetobacter xylinum phosphoglucomutase (CelB) were
      substituted by site-directed mutagenesis, resulting in mutant enzymes with Kcat
      values [glucose-1-phosphate (G-1-P) to glucose-6-phosphate] ranging from 0 to 46%
      relative to that of the wild-type enzyme. In combination with a versatile set of
      plasmid expression vectors these proteins were used in a metabolic engineering
      study on sugar catabolism in Escherichia coli. Mutants of E. coli deficient in
      phosphoglucomutase synthesize intracellular amylose when grown on galactose, due
      to accumulation of G-1-P. Wild-type celB can complement this lesion, and we show
      here that the ability of the mutant enzymes to complement is sensitive to
      variations in their respective in vitro determined Kcat and Km G-1-P values.
      Reduced catalytic efficiencies could be compensated by increasing the CelB
      expression level, and in this way a mutant protein (substitution of Thr-45 to
      Ala) displaying a 7600-fold reduced catalytic efficiency could be used to
      eliminate the amylose accumulation. Complementation experiments with the
      homologous phosphoglucomutase indicated that a Km G-1-P value significantly below
      that of CelB is not critical for the in vivo conversion of the substrate.

PMID- 10935727
TI  - Bioreactor systems in drug metabolism: synthesis of cytochrome P450-generated
      metabolites.
AB  - In this communication, we report that suspension cultures of Sf21 insect cells,
      co-infected with baculovirus containing the cDNA for a single cytochrome P450 and
      NADPH-cytochrome P450 oxidoreductase, can be employed successfully as
      "bioreactors" for the synthesis of milligram quantities of cytochrome P450
      generated metabolite(s). Three standard or probe substrates for the human P450s
      were chosen for the initial biosynthetic experiments: testosterone, diazepam, and
      diclofenac. Testosterone (100 microM, 2.88 mg/100 ml), added to a 100-ml CYP3A4
      bioreactor, was converted to 6beta-hydroxytestosterone (2.3 mg) and 15beta
      hydroxytestosterone (0.18 mg). Diazepam (100 microM, 2.9 mg/100 ml), added to a
      100-ml CYP3A4 bioreactor, was converted to temazepam (1.1 mg), N-demethyldiazepam
      (0.35 mg), and oxazepam (0.15 mg). Diclofenac (100 microM, 3.18 mg/100 ml), added
      to a 100-ml CYP2C9 bioreactor, was converted to 4'-hydroxydiclofenac (2.6 mg).
      Since the goal for the development of the bioreactors was to provide a platform
      for both the production and subsequent purification of milligram quantities of
      P450-generated metabolite(s), a second 100-ml CYP2C9 bioreactor was used for the
      large-scale production and subsequent purification of 4'-hydroxydiclofenac. After
      55 h of incubation, 7.95 mg of diclofenac was converted to 4.35 mg of 4'
      hydroxydiclofenac, while 3.55 mg of unchanged diclofenac remained in the
      bioreactor. Using a simple preparative HPLC method, approximately 2.2 mg of 4'
      hydroxydiclofenac and 1.9 mg of diclofenac were recovered from this experiment
      (28% yield). These results indicate clearly that suspension cultures of Sf21
      insect cells coexpressing a cytochrome P450 and NADPH-cytochrome P450
      oxidoreductase can be used effectively as bioreactors for the production and
      subsequent purification of milligram quantities of P450-derived metabolite(s).

PMID- 10935728
TI  - Gene therapy and metabolic engineering.
AB  - Gene therapy involves the introduction of normal, healthy genes into cells to
      correct the underlying cause of a wide variety of inherited and acquired
      diseases. Future progress in developing effective clinical protocols involving
      gene therapy for the treatment of cellular dysfunction associated with disease
      may incorporate metabolic engineering. Metabolic engineering can be applied to
      gene therapy for the successful identification of disease genes; elucidation of
      disease pathways; development of safe and efficient gene-delivery systems; and
      regulation and control of gene expression. Cystic fibrosis, cancer, and diabetes
      are reviewed as examples of diseases where gene therapy approaches are being
      studied.

PMID- 10935729
TI  - Metabolic flux analysis in Streptomyces coelicolor under various nutrient
      limitations.
AB  - Metabolic flux analysis was applied to Streptomyces coelicolor continuous culture
      data obtained under nitrogen, phosphate, sulfate, and potassium limitations. The
      metabolic reaction network involved more than 200 reactions describing the major
      pathways as well as the secondary metabolism for the production of actinorhodin
      and excretion of certain metabolites. Linear programming was used for the
      optimization of specific growth rates and energy requirements. Two types of
      specific growth rates, stoichiometric and theoretical, were defined, maximized,
      and compared in order to investigate the microbial potential. Potassium
      limitation led to the largest and nitrogen limitation to the smallest difference
      between the stoichiometric and theoretical specific growth rates. Although the
      value of the maximum theoretical specific growth rate was close to that of the
      experimental specific growth rate with potassium limitation, this difference was
      the largest in the case of nitrogen limitation. Energy requirements during
      different nutrient limitations were also investigated. The model indicated that
      although the highest actinorhodin production rate was with nitrogen limitation,
      this was accompanied with the undesired excretion of certain metabolites.

PMID- 10935730
TI  - Effect of glucose analog supplementation on metabolic flux distribution in
      anaerobic chemostat cultures of Escherichia coli.
AB  - Previous work in our laboratories investigated the use of methyl alpha-glucoside
      (alpha-MG), a glucose analog that shares a phosphotransferase system with
      glucose, to modulate glucose uptake and therefore reduce acetate accumulation.
      The results of that study showed a significant improvement in batch culture
      performance and a reduction in acetate excretion without any significant effect
      on the growth rate in complex medium. The current study investigates the effect
      of supplementing the culture medium with the glucose analog alpha-MG on the
      metabolic fluxes of Escherichia coli under anaerobic chemostat conditions at two
      different dilution rates. Anaerobic chemostat studies utilizing complex media
      supplemented with glucose or glucose and alpha-MG at dilution rates of 0.1 and
      0.4 h(-1), were performed, and the metabolic fluxes were analyzed. It was found
      that the addition of the glucose analog alpha-MG has an effect on the specific
      production rate of various extracellular metabolites. This effect is slightly
      greater at the higher dilution rate of 0.4 h(-1). However, the glucose analog
      does not cause any major shift in the central metabolic patterns. It was further
      observed that alpha-MG supplementation does not result in the reduction in
      specific acetate synthesis rate in anaerobic chemostat cultures. These results
      emphasize the importance of testing different strategies for metabolic
      manipulation under the actual operating conditions.

PMID- 10935731
TI  - [Surrogate end points].
AB  - In order to evaluate the efficacy of a treatment, "minor" end points (the
      reduction in serum cholesterol, blood pressure, serum creatinine) that have a
      pathophysiological or statistical relationship with the true end points
      (reduction in mortality, incidence of myocardial infarction, or surgical
      procedures) are often adopted. They are called surrogate end points because they
      are used instead of true end points. In cardiology the results of clinical trials
      with clofibrate, milrinone, flecainide and more recently with doxazosine have
      demonstrated that the reduction of a surrogate end point does not correspond to
      the reduction of mortality. To define a treatment for a patient, clinicians
      should distinguish surrogate from true end points choosing evidence-based
      treatments and avoiding those that are supported only by pathophysiological
      assumptions.

PMID- 10935732
TI  - [Repair of anterior mitral leaflet prolapse: state of the art].
AB  - Surgical repair of anterior leaflet prolapse has evolved and widely expanded over
      the past decade. A number of surgical techniques have been developed. In this
      study a review of all reparative techniques has been provided. A classification
      has been proposed according to the involvement of valve components and,
      eventually, to graft employment. For each technique the following points have
      been detailed: a) advantages and drawbacks; b) likelihood of effective valve
      repair based on morpho-pathologic variability of degenerative mitral disease; c)
      long-term outcome as freedom from reoperation. The authors provide indications
      for early surgical anterior leaflet prolapse repair and recommend that surgeons
      should be familiar with many reparative procedures to select the right option and
      improve their operative results.

PMID- 10935733
TI  - [Good reasons to propose to the cardiology patient a cardiologic rehabilitation
      program].
AB  - According to the latest data available, in Italy a cardiac rehabilitation program
      is currently proposed to only 17% of patients after an acute myocardial
      infarction and to 76% of patients after a coronary artery bypass grafting. One
      possible explanation for this difference is an underestimation of the
      rehabilitating techniques and some doubts about its efficacy on the quality of
      life and on secondary prevention. Regarding secondary prevention, many research
      results and independent reviews are now available and they give us the
      opportunity to develop a sufficiently evidence-based analysis of cardiac
      rehabilitation program results. Great improvements in functional capacity and
      substantial changes in the way of life seem to have been demonstrated, with good
      health oriented behaviors and improvements in the whole risk profile (less
      cigarette smoking, more sports activities, less stress, improvement in lipid
      profile). It has been well proven that with comprehensive rehabilitation
      programs, there is a relevant slow down in atherosclerosis progression.
      Rehabilitation programs also have favorable effects on the quality of life in
      patients with cardiac disorders, with fewer symptoms and more psychological and
      social well being. Three high-quality meta-analyses resulted in a significant
      reduction in total and cardiovascular mortality, mostly linked to sudden death
      and fatal reinfarction reduction, equal to the one obtained by currently
      recommended postinfarct treatments. Certainly, there are still difficulties to
      overcome before definitive conclusions can be reached, because of differences
      both in rehabilitation programs in the various studies and because of the results
      achieved in recent years through changes in the pharmacological approach to
      secondary prevention. The Global Secondary Prevention Strategies to Limit Event
      Recurrence After Myocardial Infarction (GOSPEL study) from the Italian Study
      Group on Cardiac Rehabilitation (GICR) has been designed to answer to some of
      these questions. One of its goals is to evaluate whether an intensive
      intervention of cardiac rehabilitation in the postinfarct patients is actually
      applicable and efficacious.

PMID- 10935734
TI  - [Diagnostic accuracy of exercise testing for diagnosis of coronary artery
      disease: the need for a critical review].
AB  - In this review the meaning of exercise electrocardiographic changes and
      interpretative pitfalls in particular clinical conditions are critically
      reassessed. Existing studies have been carried out on different populations and
      with different gold standards, nevertheless exercise testing if correctly
      analyzed and interpreted, can provide invaluable information for diagnosis of
      coronary artery disease. Given its feasibility, diffusion and low risk, it
      remains indeed the first choice test in the diagnostic algorithm of ischemic
      heart disease. The use of more sophisticated and expensive tests have to be
      limited to selected groups of patients in whom exercise testing, correctly
      interpreted, remains really doubtful or prematurely interrupted.

PMID- 10935735
TI  - [Appropriateness of referral to the emergency department through a telecardiology
      service. "Boario Home-Care" researchers].
AB  - BACKGROUND: The use of telemedicine appears particularly promising in
      cardiovascular diseases; it may reduce the decisional time during an acute
      myocardial infarction, which is the greater part of the so-called "avoidable
      delay" and the inappropriate admission to the Emergency Department with the
      possibility of ruling out an acute pathology. The aim of our study was to show
      the diagnostic accuracy of a telecardiology service in the daily activity of
      general practitioners. METHODS: From February 1998 to February 1999, 150 general
      practitioners received a portable electrocardiographer (Card-Guard 7100)
      transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving
      station, where a cardiologist was available for the reporting and interactive
      teleconsultation. RESULTS: During 1 year 3456 calls took place. At the time of
      the ECG recording 44% of patients were symptomatic. Chest pain was present in 669
      patients (44%), dyspnea in 21%, palpitation in 18%, dizziness in 7%, and asthenia
      in 13%. ECG and teleconsultation solved all the problems for 2452 patients (71%)
      and further diagnostic tests were requested in 862 patients (25%); 142 patients
      (4%) were sent to the Emergency Department. Cardiological diagnosis was confirmed
      in 95 patients (73%), while anxiety or gastritis were presumed in 35 patients
      (27%). In the group of patients (n = 3314) for whom the cardiologist solved the
      problem without admission to the Emergency Department, there were 5 patients who
      were admitted to the Emergency Department for myocardial ischemia in the
      following 48 hours after the teleconsultation. Telecardiology service showed
      versus Emergency Department admission a sensitivity of 95%, a specificity of
      97.5%, and a diagnostic accuracy of 92.5%. CONCLUSIONS: These data confirm a good
      diagnostic value to the service and a useful support to the general
      practitioners' activity.

PMID- 10935736
TI  - [Smoking and prevention of cardiovascular diseases in Italy. Research Group of
      the Cardiovascular Epidemiologic Observatory].
AB  - BACKGROUND: Cigarette smoking is one of the most important risk factors for
      chronic diseases. Major epidemiological studies provide consistent evidence that
      cardiovascular risk is 3-fold among smokers compared to non-smokers, incidence
      increases with the number of cigarettes smoked daily and cardiovascular risk is
      less among subjects who have stopped smoking. METHODS: To support evidence of a
      time decreasing trend of smoking habits in Italy, data from two observational
      studies carried out in different Italian regions, the RIFLE Project (1978-1987),
      the Cardiovascular Epidemiological Observatory (1998), and data collected from
      the "Multiscopo" ISTAT Investigation on Italian families (1980-1997) have been
      analyzed. RESULTS: During the 1950's, the prevalence of smokers among adult men
      was about 80%, it decreased to 50% in the 1980's and now is about 30-40%.
      Contemporarily, the prevalence of smokers among adult women has increased, from
      17% in the 1980's to 23% nowadays. The habit is more common in Central-Southern
      Italy compared to the North and is less frequent among married subjects, and male
      graduates. Learned women smoke more than those who have not received any
      education. Men begin smoking at 17-18 years, and this trend seems to have
      remained stable; on the contrary, women have changed their habits and now start
      smoking at 17 years compared to 25-30 in previous generations. Almost all smokers
      would like to stop smoking, more than 60% have tried at least once, but on
      average have lasted only for about 1 year. Passive smoking exposure varies from 1
      hour in Northern Italy to 2 hours in the South. CONCLUSIONS: Although smoking
      habits, at least in men, reveal a decreasing trend, about 30-40% of adult men
      continue to smoke. Preventive intervention, especially focused on the younger
      generations, could be useful to contrast this attitude at an early stage.

PMID- 10935737
TI  - [Epidemiologic surveillance of ischemic heart disease in the population of Pavia
      in 1986-1995].
AB  - BACKGROUND: In Italy mortality for coronary heart disease is continuously
      decreasing in males and females. However, it is not yet clear how much of this
      decline is attributable to a longer survival of coronary heart disease patients
      or to a real decreased incidence in the population. The aim of this paper was to
      analyze coronary heart disease mortality trends in the population of Pavia, case
      fatality rates and acute myocardial infarction attack rates. METHODS: Mortality
      surveillance was carried out by the Epidemiological Unit of the ASL of Pavia;
      acute myocardial infarction attack rates were estimated from regional admission
      data for the Pavia population. The target population (1991 Census) was
      represented by two groups: the first was equal to 49,326 residents (23,627 males
      and 25,699 females) 45-64 years of age, the second was equal to 17,208 residents
      (7236 males and 9972 females) 65-74 years of age. RESULTS: The decline in
      mortality was mainly observed in males aged 45-64. Acute myocardial infarction
      attack rates showed a decline in 45-64 men and an increase in the oldest age
      group. CONCLUSIONS: The surveillance of coronary heart disease epidemiological
      data from 1986 to 1995 in this population showed a decreased mortality mainly
      attributable to the decline of attack rates in the youngest and only to case
      fatality rates in the oldest age group.

PMID- 10935738
TI  - [The reform of the Italian Health Service: some concerns].
AB  - The new Italian health care reform (law 229/99) introduces relevant structural
      changes promoting a central role of the state government. We describe the reasons
      for concern caused by this administration strategy, owing also to the recent need
      for reforming the old state-centered health care service with new management
      models introduced by law 502/92. We emphasize the importance of a distinction
      between the role of physicians and their professional organizations on one side
      and the role of the administrative institutions on the other, in order to develop
      a health care system which operates correctly. We discuss the role of guidelines
      and scientific societies.

PMID- 10935739
TI  - [Dilated thyrotoxic cardiomyopathy].
AB  - We report a case of reversible, dilated cardiomyopathy due to thyrotoxicosis,
      which occurred in a young male without any underlying heart disease. The patient
      presented a clinical picture of cardiogenic shock related to severe left
      ventricular dilation and dysfunction and with new-onset atrial fibrillation and
      very high ventricular rate. In spite of vigorous medical therapy, there was only
      a mild improvement of clinical and hemodynamic status and ventricular rate
      persisted inappropriately elevated. Subsequently, laboratory test results allowed
      for recognition of thyrotoxicosis (secondary to Graves's disease) and then
      specific thyrostatic treatment was added. There was a prompt clinical improvement
      and parallel, progressive reversal of left ventricular dysfunction. The patient
      could be converted to normal sinus rhythm and one week later was discharged in
      good condition. We discuss the pathophysiological mechanism for the induction of
      this rare form of thyrotoxic cardiomyopathy and emphasize that awareness of this
      possible presentation of hyperthyroidism is essential to identify patients with
      potentially reversible dilated cardiomyopathy.

PMID- 10935740
TI  - [Is a previous neurosurgical intervention a contraindication to fibrinolytic
      therapy? Description of two cases and review of the literature].
AB  - The presence of a cerebral pathology or of previous hemorrhagic cerebrovascular
      accidents is considered a contraindication to fibrinolytic therapy during acute
      myocardial infarction due to the elevated risk of intracranial hemorrhage. Lytic
      therapy reduces early mortality by 25-50% in patients with anterior myocardial
      infarction, and logistic considerations make primary angioplasty unfeasible in
      most clinical centers. Present guidelines exclude most patients who are at risk
      of a hemorrhagic stroke from fibrinolytic therapy, depriving some of them of a
      cure which has been demonstrated to be effective. Here we describe 2 cases of
      patients who had previously been treated for cerebral aneurysms and who were
      later treated with fibrinolytics during the course of an acute myocardial
      infarction. Based on the observation of these 2 cases and on the data available
      in the literature, we identified some patients with cerebral aneurysms or
      cerebral artero-venous malformations, whose pathology, once adequately corrected,
      cannot be considered an absolute contraindication to lytic therapy in the
      presence of a large myocardial infarction, when an emergency coronary angioplasty
      cannot be performed.

PMID- 10935741
TI  - [Single-lead VDD pacing with sensing dipole in the coronary sinus: a case of
      implantation through persistent left superior vena cava].
AB  - We report the case of a VDD single-lead pacemaker implantation through a
      persistent left superior vena cava in a 48-year-old male patient with recurrent
      episodes of syncope due to paroxysmal atrioventricular block. VDD lead insertion
      through the anomalous venous structure led to positioning of the floating sensing
      dipole into the coronary sinus, in a very large and stable sensed atrial signal
      due to the close anatomic relationship between the coronary sinus and the left
      atrium. Shortness of the sensed atrioventricular interval allowed VDD stimulation
      to occur only in the case of paroxysmal atrioventricular block.

PMID- 10935742
TI  - [The International Registry of Acute Aortic Dissection (IRAD): New insights on
      aortic dissection].

PMID- 10935743
TI  - [Effect of exercise on coronary endothelial function in patients with coronary
      artery disease].

PMID- 10935744
TI  - [Thrombolytic therapy with tPA for the treatment of acute stroke. The Standard
      Treatment with Alteplase to Reverse Stroke study].

PMID- 10935745
TI  - [The BARI Investigators. Bypass treatment is better than angioplasty in reducing
      long-term mortality in diabetic patients with multivessel coronary disease].

PMID- 10935746
TI  - [Long-term survival after coronary angioplasty and aortocoronary bypass in
      patients with multivessel disease: results of the EAST study].

PMID- 10935747
TI  - [Right ventricular thrombosis and arrhythmogenic cardiomyopathy].

PMID- 10935748
TI  - [The SET-UP study].

PMID- 10935749
TI  - [The use of BP IIb/IIIa inhibitors].

PMID- 10935750
TI  - Metabolic fluxes and metabolic engineering.
AB  - Metabolic engineering is the directed improvement of cellular properties through
      the modification of specific biochemical reactions or the introduction of new
      ones, with the use of recombinant DNA technology. As such, metabolic engineering
      emphasizes metabolic pathway integration and relies on metabolic fluxes as
      determinants of cell physiology and measures of metabolic control. The
      combination of analytical methods to quantify fluxes and their control with
      molecular biological techniques to implement genetic modifications is the essence
      of metabolic engineering. Strategies for metabolic flux determination are
      reviewed in this paper and it is shown how metabolic fluxes can be used in the
      systematic elucidation of metabolic control in the framework of reaction grouping
      and top-down metabolic control analysis.

PMID- 10935751
TI  - In vivo 31P and multilabel 13C NMR measurements for evaluation of plant metabolic
      pathways.
AB  - Reliable measurements of intracellular metabolites are useful for effective plant
      metabolic engineering. This study explored the application of in situ 31P and 13C
      NMR spectroscopy for long-term measurements of intracellular pH and
      concentrations of several metabolites in glycolysis, glucan synthesis, and
      central carbon metabolic pathways in plant tissues. An NMR perfusion reactor
      system was designed to allow Catharanthus roseus hairy root cultures to grow for
      3-6 weeks, during which time NMR spectroscopy was performed. Constant cytoplasmic
      pH (7.40+/-0.06), observed during the entire experiment, indicated adequate
      oxygenation. 13C NMR spectroscopy was performed on hairy root cultures grown in
      solutions containing 1-13C-, 2-13C-, and 3-13C-labeled glucose in separate
      experiments and the flow of label was monitored. Activities of pentose phosphate
      pathways, nonphotosynthetic CO2 fixation, and glucan synthesis pathways were
      evident from the experimental results. Scrambling of label in glucans also
      indicated recycling of triose phosphate and their subsequent conversion to hexose
      phosphates.

PMID- 10935752
TI  - Metabolic flux analysis of Escherichia coli deficient in the acetate production
      pathway and expressing the Bacillus subtilis acetolactate synthase.
AB  - Several approaches to reduce acetate accumulation in Escherichia coli cultures
      have recently been reported. This reduction subsequently led to a significant
      enhancement in recombinant protein production. In those studies, metabolically
      engineered E. coli strains with reduced acetate synthesis rates were constructed
      through the modification of glucose uptake rate, the elimination of critical
      enzymes that are involved in the acetate formation pathways, and the redirection
      of carbon flux toward less inhibitory byproducts. In particular, it has been
      shown that strains carrying the Bacillus subtilis acetolactate synthase (ALS)
      gene not only produce less acetate but also have a higher ATP yield. Metabolic
      flux analysis of carbon flux distribution of the central metabolic pathways and
      at the pyruvate branch point revealed that this strain has the ability to channel
      excess pyruvate to the much less toxic compound, acetoin. The main focus of this
      study is the systematic analysis of the effects of small perturbations in the
      host's existing pathways on the redistribution of carbon fluxes. Specifically, a
      mutant with deleted acetate kinase (ACK) and acetyl phosphotransferase (PTA) was
      constructed and studied. Results from the metabolic analysis of carbon
      redistribution show the ackA-pta mutation will reduce acetate level at the
      expense of the growth rate. In addition, in the ackA-pta deficient strain a much
      higher lactate formation rate with simultaneously lower formate and ethanol
      synthesis rates was found. Expression of the B. subtilis ALS in ackA-pta mutants
      further reduces acetate levels while cell density similar to that of the parent
      strain is attained.

PMID- 10935753
TI  - Response of the central metabolism in Corynebacterium glutamicum to the use of an
      NADH-dependent glutamate dehydrogenase.
AB  - The extensive use of 13C enrichments in precursor metabolites for flux
      quantification does not rely on NADPH stoichiometries and can therefore be used
      to quantify reducing power fluxes. As an application of this concept, the NADPH
      fluxes were quantified in an L-lysine producer of Corynebacterium glutamicum
      grown into metabolic and isotopic steady state with [1-13C]glucose. In this case,
      where the organism's NADPH-dependent glutamate dehydrogenase consumes reducing
      power, the NADPH flux generated is 210% (molar flux relative to glucose uptake
      rate) with its major part (72% of the total) generated via the pentose phosphate
      pathway activity. An isogenic strain in which the glutamate dehydrogenase of C.
      glutamicum was replaced by the NADH-dependent glutamate dehydrogenase of
      Peptostreptococcus asaccharolyticus was made and the metabolite fluxes were again
      estimated. The major response to this local perturbation is a drastically reduced
      NADPH generation of only 139%. Most of the NADPH (62% of the total) is now
      generated via the tricarboxylic acid cycle activity. This shows the extraordinary
      flexibility of the central metabolism and provides a picture of the global
      regulatory properties of the central metabolism. Furthermore, a detailed analysis
      of the fluxes and exchange fluxes within the anaplerotic reactions is given. It
      is hypothesized that these reactions might also serve to balance the total
      reducing power budget as well as the energy budget within the cell.

PMID- 10935754
TI  - Oxygen consumption characteristics of porcine hepatocytes.
AB  - Oxygen uptake rate (OUR) of hepatocytes is an important parameter for the design
      of bioartificial liver assist (BAL) devices. Porcine hepatocytes were cultured in
      a specially constructed measurement chamber with an incorporated mixing system
      and a Clark polarographic oxygen electrode. Signal noise associated with
      conventional Clark electrode implementations was circumvented by the combination
      of real time digital numerical averaging and subsequent finite impulse response
      (FIR) spectral filtering. Additional software allowed for the automated
      generation of cellular oxygen consumption coefficients, namely, Vmax and K0.5,
      adding a high degree of objectivity to parameter determination. Optimization of
      the above numerical techniques identified a 0.1 Hz/200 data point sample size and
      a 0.004 Hz cutoff frequency as ideal parameters. Vmax values obtained for porcine
      hepatocytes during the first two weeks of culture showed a maximal consumption of
      0.9 nmole/sec/10(6) cells occurring on Day 4 post seeding, and a gradual decrease
      to 0.31 nmole/sec/10(6) cells by Day 15. K0.5 values increased from 2 mm Hg on
      Day 2 to 8 mm Hg by Day 8, with gradual subsequent decrease to 4 mm Hg by Day 15.
      The Vmax and K0.5 values measured for porcine cells were higher than maximal
      values for rat hepatocytes (Vmax: 0.43 nmole/sec/10(6) cells, K0.5: 5.6 mmHg) and
      thus may necessitate significantly altered BAL device design conditions to ensure
      no oxygen limitations. Finally, these results highlight the need for species
      specific characterization of cellular function for optimal BAL device
      implementations.

PMID- 10935755
TI  - Microbial conversion of indene to indandiol: a key intermediate in the synthesis
      of CRIXIVAN.
AB  - Indene is oxidized to mixtures of cis- and trans-indandiols and related
      metabolites by Pseudomonas putida and Rhodococcus sp. isolates. Indene metabolism
      is consistent with monooxygenase and dioxygenase activity. P. putida resolves
      enantiomeric mixtures of cis-1,2-indandiol by further selective oxidation of the
      1R, 2S-enantiomer yielding high enantiomeric purity of cis-(1S, 2R)-indandiol, a
      potential intermediate in the synthesis of indinavir sulfate (CRIXIVAN), a
      protease inhibitor used in the treatment of AIDS. Molecular cloning of P. putida
      toluene dioxygenase in Escherichia coli confirmed the requirement for the
      dihydrodiol dehydrogenase in resolving racemic mixtures of cis-indandiol.
      Rhodococcus sp. isolates convert indene to cis-(1S, 2R)-indandiol at high initial
      enantiomeric excess and one isolate also produces trans-(1R, 2R)-indandiol,
      suggesting the presence of monooxygenase activity. Scale up and optimization of
      the bioconversions to these key synthons for chiral synthesis of potential
      intermediates for commercial manufacture of indinavir sulfate are described.

PMID- 10935756
TI  - Nonlinear metabolic control analysis.
AB  - Mathematical description of metabolic systems allows the calculation of the
      expected responses of metabolism to genetic modifications and the identification
      of the most promising targets for metabolic engineering. Metabolic control
      analysis (MCA) provides such a description in the form of quantitative indices
      (elasticities and control coefficients). These indices are determined by
      perturbation experiments around a reference steady state and, therefore, the
      predictive power of MCA is limited to small changes in the metabolic parameters.
      The modeling framework introduced here allows accurate description of the
      metabolic responses over wide range of changes in the metabolic parameters. The
      framework requires information about the MCA indices at the reference state and
      the corresponding values of the metabolic reaction rates, and employs simplifying
      assumptions about the reaction mechanisms. It is shown that knowledge of the
      intracellular metabolite concentrations is not necessary for the application of
      the framework. The performance of the methodology is illustrated using three
      elementary metabolic systems that display highly nonlinear responses to the
      modification in their parameters: an unbranched pathway, an interconvertible
      enzyme system, and a branched pathway subject to feedback inhibition.

PMID- 10935757
TI  - Metabolic engineering from a cybernetic perspective: aspartate family of amino
      acids.
AB  - Using the modular cybernetic framework developed by Varner and Ramkrishna (Varner
      and Ramkrishna; 1998a, b) a cybernetic model is formulated that describes the
      time evolution of the aspartate family of amino acids in Corynebacterium
      lactofermentum ATCC 21799. The network model formulation is employed in the role
      of a diagnostic tool for the overproduction of threonine. More precisely, having
      determined a parameter set that describes the time evolution of a base strain
      (lysine producer), the model predicted response to genetic perturbations,
      designed to enhance the level of threonine, are simulated using an appropriately
      modified cybernetic model and compared with the experimental results of
      Stephanopoulos and Sinskey (Colon et al., 1995a, Appl. Environ. Microbiol. 61, 74
      78) for identical genetic perturbations. It is found that the model predicted
      response to enzymatic over-expression in the aspartate pathway agrees, for the
      most part, with experimental observations within the experimental error bounds.
      This result lends credence to the hypothesis that cybernetic models can be
      employed to predict the local response of a metabolic network to genetic
      perturbation, thereby, affording cognizance of the potential pitfalls of a
      particular genetic alteration strategy a priori.

PMID- 10935758
TI  - An efficient neural network approach to dynamic robot motion planning.
AB  - In this paper, a biologically inspired neural network approach to real-time
      collision-free motion planning of mobile robots or robot manipulators in a
      nonstationary environment is proposed. Each neuron in the topologically organized
      neural network has only local connections, whose neural dynamics is characterized
      by a shunting equation. Thus the computational complexity linearly depends on the
      neural network size. The real-time robot motion is planned through the dynamic
      activity landscape of the neural network without any prior knowledge of the
      dynamic environment, without explicitly searching over the free workspace or the
      collision paths, and without any learning procedures. Therefore it is
      computationally efficient. The global stability of the neural network is
      guaranteed by qualitative analysis and the Lyapunov stability theory. The
      effectiveness and efficiency of the proposed approach are demonstrated through
      simulation studies.

PMID- 10935759
TI  - A neural network theory of proportional analogy-making.
AB  - A neural network model that can simulate the learning of some simple proportional
      analogies is presented. These analogies include, for example, (a) red-square:red
      circle :: yellow-square:?, (b) apple:red :: banana: ?, (c) a:b :: c:?. Underlying
      the development of this network is a theory for how the brain learns the nature
      of association between pairs of concepts. Traditional Hebbian learning of
      associations is necessary for this process but not sufficient. This is because it
      simply says, for example, that the concepts "apple" and "red" have been
      associated, but says nothing about the nature of this relationship. The types of
      context-dependent interlevel connections in the network suggest a semilocal type
      of learning that in some manner involves association among more than two nodes or
      neurons at once. Such connections have been called synaptic triads, and related
      to potential cell responses in the prefrontal cortex. Some additional types of
      connections are suggested by the problem of modeling analogies. These types of
      connections have not yet been verified by brain imaging, but the work herein
      suggests that they may occur and, possibly, be made and broken quickly in the
      course of working memory encoding. These working memory connections are referred
      to as differential, delayed and anti-Hebbian connections. In these connections,
      one can learn transitions such as "keep red the same"; "change red to yellow";
      "turn off red"; "turn on yellow," and so forth. Also, included in the network is
      a kind of weight transport so that, for example, red to red can be transported to
      a different instance of color, such as yellow to yellow. The network
      instantiation developed here, based on common connectionist building blocks such
      as associative learning, competition, and adaptive resonance, along with
      additional principles suggested by analogy data, is a step toward a theory of
      interactions among several brain areas to develop and learn meaningful
      relationships between concepts.

PMID- 10935760
TI  - Generic modeling of chemotactic based self-wiring of neural networks.
AB  - The proper functioning of the nervous system depends critically on the intricate
      network of synaptic connections that are generated during the system development.
      During the network formation, the growth cones migrate through the embryonic
      environment to their targets using chemical communication. A major obstacle in
      the elucidation of fundamental principles underlying this self-wiring is the
      complexity of the system being analyzed. Hence much effort is devoted to in vitro
      experiments of simpler (two-dimensional) 2D model systems. In these experiments
      neurons are placed on Poly-L-Lysine (PLL) surfaces, so it is easier to monitor
      their self-wiring. We developed a model to reproduce the salient features of the
      2D systems, inspired by the study of the growth of bacterial colonies and the
      aggregation of amoebae. We represent the neurons (each composed of cell's soma,
      neurites and growth cones) by active elements that capture the generic features
      of the real neurons. The model also incorporates stationary units representing
      the cells' soma and communicating walkers representing the growth cones. The
      stationary units send neurites one at a time, and respond to chemical signaling.
      The walkers migrate in response to chemotaxis substances emitted by the soma and
      communicate with each other and with the soma by means of chemotactic "feedback".
      The interplay between the chemo-repulsive and chemo-attractive responses is
      determined by the dynamics of the walker's internal energy which is controlled by
      the soma. These features enable the neurons to perform the complex task of self
      wiring. We present numerical experiments of the model to demonstrate its ability
      to form fine structures in simple networks of few neurons. Our results raise two
      fundamental issues: (1) one needs to develop characterization methods (beyond
      number of connections per neuron) to distinguish the various possible networks;
      (2) what are the relations between the network organization and its computational
      properties and efficiency?

PMID- 10935761
TI  - Hard-wired models of working memory and temporal sequence storage and generation.
AB  - We develop hard-wired simulations of temporal sequence storage and generation by
      multi-modular networks based on the frontal lobe system (cortex, basal ganglia
      and thalamus). Single cell activity is shown to have been constructed so as to
      mimic results measured in monkeys on a similar task, indicating that a suitable
      form of chunking had been achieved in the models. The mathematical nature of
      these processes is discussed, from the viewpoint of bifurcation theory.

PMID- 10935762
TI  - A recurrent model of transformation invariance by association.
AB  - This paper describes an investigation of a recurrent artificial neural network
      which uses association to build transform-invariant representations. The
      simulation implements the analytic model of Parga and Rolls [(1998). Transform
      invariant recognition by association in a recurrent network. Neural Computation
      10(6), 1507-1525.] which defines multiple (e.g. "view") patterns to be within the
      basin of attraction of a shared (e.g. "object") representation. First, it was
      shown that the network could store and correctly retrieve an "object"
      representation from any one of the views which define that object, with capacity
      as predicted analytically. Second, new results extended the analysis by showing
      that correct object retrieval could occur where retrieval cues were distorted;
      where there was some association between the views of different objects; and
      where connectivity was diluted, even when this dilution was asymmetric. The
      simulations also extended the analysis by showing that the system could work well
      with sparse patterns; and showing how pattern sparseness interacts with the
      number of views of each object (as a result of the statistical properties of the
      pattern coding) to give predictable object retrieval performance. The results
      thus usefully extend a recurrent model of invariant pattern recognition.

PMID- 10935763
TI  - Universal learning network and its application to chaos control.
AB  - Universal Learning Networks (ULNs) are proposed and their application to chaos
      control is discussed. ULNs provide a generalized framework to model and control
      complex systems. They consist of a number of inter-connected nodes where the
      nodes may have any continuously differentiable nonlinear functions in them and
      each pair of nodes can be connected by multiple branches with arbitrary time
      delays. Therefore, physical systems, which can be described by differential or
      difference equations and also their controllers, can be modeled in a unified way,
      and so ULNs may form a super set of neural networks and fuzzy neural networks. In
      order to optimize the ULNs, a generalized learning algorithm is derived, in which
      both the first order derivatives (gradients) and the higher order derivatives are
      incorporated. The derivatives are calculated by using forward or backward
      propagation schemes. These algorithms for calculating the derivatives are
      extended versions of Back Propagation Through Time (BPTT) and Real Time Recurrent
      Learning (RTRL) of Williams in the sense that generalized node functions,
      generalized network connections with multi-branch of arbitrary time delays,
      generalized criterion functions and higher order derivatives can be deal with. As
      an application of ULNs, a chaos control method using maximum Lyapunov exponent of
      ULNs is proposed. Maximum Lyapunov exponent of ULNs can be formulated by using
      higher order derivatives of ULNs, and the parameters of ULNs can be adjusted so
      that the maximum Lyapunov exponent approaches the target value. From the
      simulation results, it has been shown that a fully connected ULN with three nodes
      is able to display chaotic behaviors.

PMID- 10935764
TI  - A novel network for nonlinear modeling of neural systems with arbitrary point
      process inputs.
AB  - This paper address the issue of nonlinear model estimation for neural systems
      with arbitrary point-process inputs using a novel network that is composed of a
      pre-processing stage of a Laguerre filter bank followed by a single hidden layer
      with polynomial activation functions. The nonlinear modeling problem for neural
      systems has been attempted thus far only with Poisson point-process inputs and
      using cross-correlation methods to estimate low-order nonlinearities. The
      specific contribution of this paper is the use of the described novel network to
      achieve practical estimation of the requisite nonlinear model in the case of
      arbitrary (i.e. non-Poisson) point-process inputs and high-order nonlinearities.
      The success of this approach has critical implications for the study of neuronal
      ensembles, for which nonlinear modeling has been hindered by the requirement of
      Poisson process inputs and by the presence of high-order nonlinearities. The
      proposed methodology yields accurate models even for short input-output data
      records and in the presence of considerable noise. The efficacy of this approach
      is demonstrated with computer-simulated examples having continuous output and
      point-process output, and with real data from the dentate gyrus of the
      hippocampus.

PMID- 10935765
TI  - Percutaneous coronary interventions without surgical back-up--are they safe?

PMID- 10935766
TI  - Community prevention of cardiovascular disease: how much do we know?

PMID- 10935767
TI  - Ischaemic preconditioning in cardiopulmonary bypass surgery.

PMID- 10935768
TI  - New aspects of myocardial oxygen consumption. Invited review.
AB  - This paper gives an overview of mainly new aspects of myocardial oxygen
      consumption. Experimental models have quantified energy consumption in mechanical
      work, excitation-contraction coupling and metabolic processes. However, there are
      still contradictory observations between hemodynamic, thermodynamic and
      subcellular models and further knowledge of subcellular energy consumption is
      anticipated. The energy cost of contractility-enhancing drugs has been
      investigated in various experimental and clinical studies, and the calcium
      sensitizers have been proven to be the most mechanoenergetically efficient. An
      "oxygen-wasting" effect in post-ischemic hearts was observed some 15 years ago.
      The mechanism for this inefficiency has been thoroughly investigated, and seems
      to be caused by an inefficient excitation-contraction coupling and/or
      inefficiency in the contractile apparatus. The mechanoenergetic efficiency in
      heart failure needs further investigation.

PMID- 10935769
TI  - Emergency coronary artery bypass surgery after failed percutaneous transluminal
      coronary angioplasty.
AB  - Coronary complications caused by percutaneous transluminal coronary angioplasty
      (PTCA) may necessitate emergency coronary artery bypass grafting (CABG). In 1994
      1998, 132 patients (1.5% of the patients registered in the Danish PTCA registry)
      underwent CABG within 24 h because of angioplasty complications. We reviewed the
      files of 86 patients who had emergency operations within 6 h and found that 35%
      suffered from 1-vessel disease. Fifty-eight percent were taken directly to the
      operating room from the cardiovascular laboratory, and 13% were given
      preoperative cardiovascular resuscitation. The vessels most frequently injured
      were the right coronary artery and the left anterior descending branch (LAD). The
      patients received a mean of 2.4 coronary bypasses each. Forty-three percent of
      the patients with lesions of the left main coronary artery and/or the LAD
      received a vein graft to the LAD. A perioperative Q-wave myocardial infarction
      developed in 51% of the patients. The in-hospital mortality rate was 12%. These
      results are inferior to those obtained after elective surgery. Local
      cardiothoracic backup is vital when PTCA is performed in an unselected patient
      group.

PMID- 10935770
TI  - Ischaemic preconditioning has a beneficial effect on left ventricular
      haemodynamic function after a coronary artery biopass grafting operation.
AB  - OBJECTIVE: Ischaemic preconditioning (IP) is the most effective procedure for
      endogenous myocardial protection. However, studies on the effects of IP in
      cardiac surgery are rare and controversial. The present aim was to investigate
      whether IP improves the haemodynamic recovery of CABG patients. DESIGN: The study
      included 40 stable CABG patients with 3-vessel disease, randomized into an IP
      group (n = 20) and a control group (n = 20). In the IP group two cycles of 2-min
      ischaemia following 3-min reperfusion before cross-clamping were induced. The
      haemodynamics of the patients were followed-up to the first postoperative
      morning. RESULTS: The cardiac index decreased at 1 and 6 h after surgery in the
      control group but increased in the IP group (-0.33 vs 0.09 l/min/m2, p = 0.02 and
      -0.15 vs 0.57 l/min/m2, p = 0.001, respectively). Depressions in the left
      ventricular stroke work index and the right ventricular stroke work index at 6 h
      after surgery were more severe in controls and were statistically significant (p
      = 0.049 and 0.007, respectively). Less inotropic support was used in the IP
      group. There were no differences in serum CK-MB, cardiac troponin I, myoglobin or
      lactate values between the two groups. CONCLUSION: IP has a beneficial effect on
      left ventricular haemodynamic recovery after a CABG operation.

PMID- 10935771
TI  - Short-term physical training reduces left ventricular dilatation during exercise
      soon after myocardial infarction.
AB  - Coronary heart disease and beta-blocker treatment can increase the use of the
      Frank-Starling mechanism during exercise. The aim of the study was to assess
      whether this could be influenced by physical training. Male patients on beta
      blocker treatment after myocardial infarction were randomised to four weeks of
      training (ET, n = 19) or to a control group (Ctr, n = 18). Cardiac output (CO) at
      rest and at identical submaximal exercise levels in each patient were determined
      by radionuclide ventriculography at baseline and after the intervention period.
      CO was calculated as end diastolic volume (EDV) x ejection fraction x heart rate,
      and deltaCO and deltaEDV as change in parameter from rest to exercise. The mean
      (SD) deltaCO decreased from 6.5 (2.1) L/min(-1) to 5.1 (2.4) in ET patients and
      increased from 5.0 (1.7) to 5.8 (2.7) in Ctr, p = 0.004. deltaEDV decreased from
      30 (30) mL to 12 (35) in ET and increased from 11 (20) to 36 (33) in Ctr, p =
      0.005. When adjusting for baseline dissimilarities between the groups in a
      multivariate linear regression analysis, these differences were still
      statistically significant, p = 0.018 and p = 0.044, respectively. Physical
      training reduces the CO increase needed to perform identical submaximal exercise,
      and this is accompanied by less left ventricular dilatation, with a potential for
      reducing exercise-induced ischaemia.

PMID- 10935772
TI  - Spectral turbulence and late potentials in the signal-averaged electrocardiograms
      of patients with monomorphic ventricular tachycardia versus resuscitated
      ventricular fibrillation.
AB  - Signal-averaged electrocardiograms (SAECG) were analyzed for late potentials and
      spectral turbulence in 208 patients with ischemic heart disease with a history of
      sustained monomorphic ventricular tachycardia (MVT) (n = 62), resuscitation from
      ventricular fibrillation (VF) (n = 64) or no ventricular tachyarrhythmia (n =
      82). Receiver operating characteristic curves were utilized to optimize cut-off
      values for prediction of MVT and VF. Patients with MVT had a lower ejection
      fraction (mean = 0.37) than patients with VF (0.44; p = 0.01) and controls (0.48;
      p < 0.0001). The mean FQRSD in MVT patients (126 ms) was longer than in VF and
      controls (113 ms; p = 0.005 and 102 ms; p < 0.0001, respectively). The RMS40 was
      lower in MVT (19 microV) than in VF and controls (29 microV; p = 0.0003 and 28
      microV; p < 0.0001, respectively); 81% of the MVT patients were spectral
      turbulence-positive vs 47% of VF patients and 31% of control patients (p < 0.0001
      for both differences). With optimized reference values, FQRSD, TQRSD and ISCSD
      contributed significantly to the identification of MVT patients and FQRSD to VF
      patients. The sensitivity of combined time-domain and spectral turbulence
      analysis was 90% for MVT and 58% for VF, with 63% specificity. MVT patients had a
      lower ejection fraction and were more often late potential and spectral
      turbulence positive than VF and control patients. These findings indicate that a
      large electroanatomic substrate is required in MVT. A long FQRSD was a risk
      marker for both MVT and VF. Spectral turbulence analysis added independent
      information, and the combination of time-domain and spectral turbulence analysis
      was superior to either method alone in identifying the MVT patients. Neither
      method of analysis, singly nor in combination, performed satisfactorily in
      identification of VF risk.

PMID- 10935774
TI  - A typical P-wave morphology in incessant atrial tachycardia originating from the
      right upper pulmonary vein.
AB  - Automatic atrial tachycardias often originate from the ostia of the pulmonary
      veins. P-wave morphology during tachycardia may indicate from which pulmonary
      vein the tachycardia originates. Two patients with pulmonary vein tachycardias
      demonstrating atypical P-wave morphology were investigated. One of the patients
      had a tachycardia with two different cycle lengths. P-wave morphology was
      evaluated in 12-lead ECGs from two patients with incessant atrial tachycardia,
      during tachycardia and sinus rhythm. Their tachycardias were successfully ablated
      at the mouth of the right upper pulmonary vein. Previous studies have
      demonstrated a positive or negative P-wave configuration in lead aVL originating
      from this area and a change from a biphasic P-wave in V1 during sinus rhythm to a
      positive P-wave configuration during tachycardia. Neither of our two patients had
      such a change in lead V1. One our patients had two tachycardias with different
      cycle lengths originating from the same area. It is concluded that if an atrial
      tachycardia with P-wave morphology resembling that of sinus rhythm cannot be
      located to the right atrium, its origin may be the right upper pulmonary vein.

PMID- 10935773
TI  - Cardiac rhythm in patients with sleep-disordered breathing and coronary artery
      disease.
AB  - We examined the effect of sleep-disordered breathing on heart rates and
      arrhythmias in men and women with disabling angina pectoris and verified coronary
      artery disease by an overnight sleep study and Holter recording. The number of
      oxyhaemoglobin desaturations > or =4% (ODI) and number of apnoea-hypopnoeas per
      hour of sleep (AHI) were recorded. ODI > or =5 and AHI > or =10 were used as
      measures of disordered breathing and patients below these limits formed the
      control groups. One-hundred and forty-one men and 98 women < or =70 years of age
      were randomly included. Thirty-eight percent of the men and 36% of the women had
      an ODI > or =5. No serious ventricular arrhythmias occurred. Women with
      disordered breathing (ODI > or =5) had higher heart rates (mean 63.3 vs 59.1, p <
      0.05) and a higher occurrence of ventricular premature contractions (VPCs) during
      sleep (75th percentiles 2.5 vs 0.5 per hour, p < 0.01). In men, however, no
      significant association between disordered breathing and heart rates or
      arrhythmias was found. We conclude that serious arrhythmias are infrequent in
      unselected patients with coronary artery disease and mild to moderate sleep
      disordered breathing. Disordered breathing in women is associated with higher
      heart rates and a higher occurrence of VPCs during sleep.

PMID- 10935775
TI  - Screening for pulmonary arteriovenous malformations: contrast echocardiography
      versus pulse oximetry.
AB  - Pulmonary arteriovenous malformations (PAVM) cause right-to-left shunt and imply
      risk of paradoxical embolism and cerebral abscess. These complications can be
      prevented by appropriate treatment. Detection of PAVMs is therefore important, so
      simple and reliable screening methods are needed for this purpose. The aim of
      this investigation was to compare pulse oximetry and contrast echocardiography as
      screening tools for detection of pulmonary arteriovenous malformations. Eighty
      five hereditary haemorrhagic telangiectasia (HHT) patients and first-degree
      relatives identified in a comprehensive study of HHT-families in the county of
      Funen, Denmark, were investigated. Standing and supine pulse oximetry in room air
      was performed in all subjects, and in subjects with symptoms and/or abnormal
      pulse oximetry in room air, supine pulse oximetry breathing 100% oxygen was also
      performed. Transthoracic echocardiography with intravenous injection of echo
      contrast was performed in all subjects. Outcome measures were oxygen saturation
      change >2% units on changing body position and echo contrast observed in the left
      sided heart chambers. Positive contrast echocardiography indicating the presence
      of PAVM was found in 47 subjects, whereas pulse oximetry was abnormal in only 16.
      The results strongly suggest that contrast echocardiography is a more sensitive
      screening tool for PAVMs than pulse oximetry.

PMID- 10935776
TI  - Regional variations in the use of diagnostic coronary angiography. A one-year
      population-based study of all diagnostic coronary angiographies performed in a
      rural and an urban Danish county.
AB  - The aim of this study was to monitor coronary angiography activity and results,
      and to evaluate indications and treatment consequences using regional hospital
      registers and case records in the rural county of Ringkjobing and urban county of
      Aarhus The study included all patients who had undergone a coronary angiography
      during 1996. For women, there were 606 (rural) and 1296 (urban) coronary
      angiographies per one million inhabitants (p < 0.0001) and for men, 1884 (rural)
      and 3051 (urban) coronary angiographies per one million inhabitants (p < 0.0001).
      In both counties the age distribution of the women examined was the same as that
      for the men. The angiographic rates were the same in the two counties for
      patients examined for valvular heart disease and severe arrhythmias. For patients
      with ischaemic heart disease, the angiographic rate for rural patients was two to
      three times lower than that for urban patients (p < 0.01). Revascularization
      procedures were performed in 39% (rural) and 40% (urban) of the examined women
      (NS) and 66% (rural) and 59% (urban) of the examined men (p < 0.05). Despite wide
      regional differences in coronary angiography activity, angiography was deployed
      to the same extent for examination of patients with valvular and severe
      arrhythmia heart disease. For patients examined for ischaemic heart disease,
      angiography activity was considerably lower in the rural area. The female
      patients had a higher frequency of normal coronary angiograms than the male
      patients.

PMID- 10935777
TI  - The value of repeated echocardiographic evaluation in patients with idiopathic
      dilated cardiomyopathy during treatment with metoprolol or captopril.
AB  - Serial echocardiographic investigations were carried out on patients with
      idiopathic dilated cardiomyopathy, to evaluate treatment effects on left
      ventricular (LV) performance during therapy with either metoprolol or captopril.
      Thirty-two patients (23 males and 9 females) with mild to moderate symptoms of
      heart failure (NYHA II-III) and a mean age of 49 years were included in the
      investigation. The patients were investigated with Doppler echocardiography
      before treatment, after 3 and 6 months of treatment (either metoprolol or
      captopril) and 1 month after withdrawal of treatment. Intra- and inter
      investigator reproducibility was acceptable, with a coefficient of variation of
      less than 5% for LV dimensions. A reduction in LV dimensions was seen in both
      treatment groups. In the metoprolol group there was also an increase in LV stroke
      volume and fractional shortening. The non-invasive data were in accordance with
      invasive measurements of stroke volume and LV filling pressure. In patients with
      idiopathic dilated cardiomyopathy and mild to moderate symptoms of heart failure,
      echocardiography seemed to be sufficiently reproducible to be used for
      determination of treatment effects in a longitudinal heart failure study. Both
      metoprolol and captopril were well tolerated and had favourable effects on LV
      performance.

PMID- 10935778
TI  - Platelet retention in coronary artery bypass surgery with and without a heart
      lung machine. Cause of thrombosis in coronary artery bypass surgery.
AB  - The aim of this study was to examine platelet function after coronary artery
      bypass grafting (CABG) with and without the use of extracorporeal circulation
      (ECC). Sixteen male patients scheduled for CABG with (n = 8) and without (n = 8)
      ECC were included in the study. Platelet retention, as measured with a glass-bead
      retention test, was examined daily during the first postoperative week. Von
      Willebrand factor (vWF), ristocetin co-factor (Rcof) and prothrombin fragment (PF
      1 + 2) were analyzed the day after the operation. We found a significant increase
      (p < 0.0001) in platelet retention during the first postoperative week after
      CABG. There was a tendency (not statistically significant) towards a more
      pronounced increase in the group operated on without ECC. This increase occurred
      despite the fact that all patients were treated with aspirin (75 mg daily) from
      the first postoperative day. The median time to maximal postoperative platelet
      retention was 2 days. In 3 patients platelet retention increased to more than 6
      times the basal level.

PMID- 10935779
TI  - Effects of cardiac surgery on some clinically used inflammation markers and
      procalcitonin.
AB  - One hundred and ten patients were investigated prospectively in a study aimed at
      creating reference curves for inflammation markers (serum C-reactive protein
      (CRP), blood leukocyte count, iron, transthyretin and procalcitonin). Blood
      samples were taken daily and the patients were monitored for signs of infection.
      Ninety-six patients had no postoperative infections. CRP and leukocyte counts
      peaked on the third and second postoperative days, respectively. Neither patients
      operated on off-pump (n = 4) nor patients with minor infections (n = 11) differed
      from the non-infected group. Two out of three patients with major postoperative
      infection exhibited a secondary peak in CRP and leukocyte count. Iron and
      transthyretin decreased initially, followed by a slow increase without any
      difference between the groups. Procalcitonin was high in some non-infected
      patients and low in some infected patients. CRP and leukocyte count had a
      predictable course with a secondary peak in major infections but the other
      markers did not provide any valuable information.

PMID- 10935780
TI  - Influence of hemofiltration on plasma cytokine levels and platelet activation
      during extra corporeal membrane oxygenation.
AB  - OBJECTIVE: Extra corporeal circulation of human blood is used daily in lifesaving
      procedures such as open-heart surgery and extracorporeal membrane oxygenation
      (ECMO). But extracorporeal circulation also induces activation of various cascade
      reactions in the blood. The objective of this study was to evaluate the effects
      of hemofiltration on cytokine release and removal as well as on platelet
      activation and consumption. MATERIAL AND METHODS: Two complete ECMO systems, each
      of them holding a hollow fiber oxygenator, a bladder box, PVC tubing and a roller
      pump were perfused for 24 h with fresh, heparinized human blood. A hemofilter was
      added to one of the paired systems. Blood samples were collected from both
      circuits before start, and at 0.5, 1, 3, 12 and 24 h of perfusion. A total of 8
      paired experiments was performed. RESULTS: The plasma concentration of
      interleukin (IL)1beta, IL-6 and IL-8, as well as of IL-1 receptor antagonist (IL
      1ra) increased over time in both systems, but consistently lower levels were
      observed in the filter circuits compared to the controls. Only minor parts of
      these cytokines could be assayed in the ultrafiltrate. No significant difference
      in platelet count and platelet membrane expression of glycoprotein Ib was
      observed between the circuits. CONCLUSIONS: By adding a hemofilter to the ECMO
      circuit, it is possible to reduce the plasma concentration of interleukins
      without significantly affecting platelet activation and consumption.

PMID- 10935781
TI  - Insulin(GIK) improves myocardial metabolism in patients during blood
      cardioplegia.
AB  - The aim of this study was to test the hypothesis that abnormalities of myocardial
      substrate metabolism during blood cardioplegic aortic cross-clamping and early
      reperfusion are attenuated further by insulin(GIK) than by alpha-ketoglutarate
      enrichment of blood cardioplegia alone. Twenty-eight males (47 to 78 years)
      undergoing coronary artery bypass grafting (CABG) participated in a prospective,
      controlled, randomized study. All patients had alpha-ketoglutarate-enriched blood
      cardioplegia. Insulin(GIK) was infused in 13 patients during aortic cross
      clamping. Insulin(GIK) prevented lactate release during cardioplegia (1.5+/-15 vs
      -44+/-14 micromol/min, p = 0.04), and a significant extraction of lactate was
      induced shortly after declamping the aorta (15+/-3 vs 2+/-1%, p = 0.001). Free
      fatty acid uptake was reduced after cardioplegic cross-clamping (5.7+/-1.6 vs
      16.0+/-3.8 micromol/min, p = 0.02). More positive/less negative levels of
      alanine, aspartate, glutamine, glycine, ornithine, taurine and tyrosine were
      found in all the insulin-treated patients. We conclude that insulin(GIK)
      attenuates abnormalities of myocardial substrate metabolism during blood
      cardioplegic aortic cross-clamping and early reperfusion further than is obtained
      with alpha-ketoglutarate enrichment of blood cardioplegia alone.

PMID- 10935782
TI  - Lack of effect of synthetic pericardial substitute on right ventricular function
      after coronary artery bypass surgery. An echocardiographic and magnetic resonance
      imaging study.
AB  - Abnormal right heart function after cardiac surgery is a well-known finding.
      Inadequate preservation during the operation and restricted cardiac motion due to
      pericardial adhesions have been proposed as underlying mechanisms. This study
      focuses on the impact of a pericardial substitute implantation on right
      ventricular function, using echocardiography and magnetic resonance imaging. A
      test group of six patients (mean age 54 years) was examined before surgery, and 4
      15 days and 5-9 months after coronary artery bypass surgery, where the
      pericardium was closed with a biodegradable pericardial patch. A group of 11
      patients (mean age 63 years) in whom the pericardium was left open served as
      controls. Tricuspid annulus motion was markedly decreased, abnormal septal motion
      was present and decreased systolic to diastolic ratio in the vena cava superior
      flow was present in all patients in both groups one week after surgery. At the
      late follow-up, all patients still had decreased tricuspid annulus motion, while
      17% of the patients in the test group and 22% of the patients in the control
      group (ns) demonstrated normal septal motion. We conclude that closing the
      pericardium with a biodegradable patch does not affect the postoperative changes
      in right heart function normally seen after open-heart surgery.

PMID- 10935783
TI  - Evaluation of pulmonary gas exchange after lobectomy and simple thoracotomy.
AB  - Postoperative influence of simple thoracotomy and lobectomy on pulmonary gas
      exchange was investigated in 10 patients undergoing thoracotomy and lobectomy (L
      group) and 10 patients with simple thoracotomy (ST group). Gas exchange was
      assessed with hot-wire mass spectrometry and blood gas analyses preoperatively
      and postoperatively at 1, 3, 6, 12, 24 and 48 h and on days 4, 6 and 13. The
      preoperative values of alveolar-arterial oxygen tension gradient (AaDO2),
      ventilation-perfusion mismatch (V(A)/Q) and circulatory shunt (Qs/Qt) were
      maintained in the ST group. In the L group, however, AaDO2 and Qs/Qt showed good
      maintenance of gas exchange for only 6-12h after lobectomy and then deteriorated
      because of peripheral atelectasis, resulting in poorer values than those in the
      ST group on days 4 and 13. Careful postoperative management, including pulmonary
      toilet, is essential for maintenance of gas exchange and prevention of pulmonary
      complications.

PMID- 10935784
TI  - Laser Doppler flowmetry detects early risk of tracheal anastomotic complications
      after lung transplantation.
AB  - Healing of tracheal anastomosis after en bloc double-lung or heart-lung
      transplantation was analysed with the aid of endoscopic laser Doppler flowmetry
      in 7 patients (group I) with successful bronchial artery revascularization (BAR)
      and in 5 patients (group II) without or with failed BAR. Fifteen patients
      undergoing coronary surgery served as a control group. Airway anastomotic index
      (AAI) was used to express the ratio of Doppler flowmetry values between donor and
      recipient airway. On postoperative day 1 the mean (range) AAI was 1.3 (1.1-1.6)
      in group I, 0.74 (0.25-1.0) in group II and 0.95 (0.7-1.4) in the controls.The
      difference was statistically significant between groups I and II (p = 0.01) and
      also between group I and the control group (p = 0.003). Two group II patients had
      low AAI (<0.5), and both developed airway anastomotic complications. We conclude
      that successful BAR increases blood flow in the airway anastomotic region, and
      that low AAI on the first postoperative day is a strong predictor of late airway
      anastomotic complications.

PMID- 10935785
TI  - Flow cytometric analysis in diagnosis of thymoma metastases.
AB  - Thymomas are relatively rare tumours of the anterior mediastinum, constituting
      approximately 10-15% of all mediastinal tumours. In contrast to other neoplasms,
      they rarely present distant metastases. We describe a case of thymoma with long
      survival and skin metastases diagnosed by two-colour flow cytometry.

PMID- 10935786
TI  - Laparoscopic microwave coagulation therapy for hepatocellular carcinoma.
AB  - BACKGROUND AND STUDY AIMS: Several different effective forms of treatment are
      available, singly or in combination, for patients with hepatocellular carcinoma
      (HCC). These include surgical resection, transcatheter arterial embolization,
      percutaneous ethanol injection, and percutaneous microwave coagulation therapy.
      In this study, we carried out laparoscopic microwave coagulation therapy (LMCT),
      using laparoscopic microwave electrodes to treat HCC. PATIENTS AND METHODS: Under
      local anesthesia, 24 patients with HCCs located on or near the liver surface
      underwent LMCT under direct laparoscopic vision, with ultrasound guidance. LMCT
      was performed using microwave electrodes with tips ranging from 15-45 mm in
      length, and the effectiveness of the treatment was confirmed using contrast
      enhanced computed tomography (CT) within two weeks of the LMCT procedure.
      RESULTS: The mean longest axis of the 26 HCC nodules in 24 patients was 20 mm,
      and that of the coagulated areas including the nodules was 40 mm, with additional
      therapy being required in two patients. Complete efficacy of the treatment was
      observed in 21 patients (87.5%), but local recurrences were seen in three of them
      one year after LMCT. The three-year survival rate was 92%, but the number of
      patients included in the study was small. Hemostasis was complete, but mild
      pneumothorax occurred in three patients. CONCLUSIONS: LMCT under local anesthesia
      is a minimally invasive and effective therapy when carried out on a single
      occasion to treat HCCs located near the liver surface, and it can be safely
      performed under direct visual guidance.

PMID- 10935787
TI  - Value of laparoscopic microwave coagulation therapy for hepatocellular carcinoma
      in relation to tumor size and location.
AB  - BACKGROUND AND STUDY AIMS: The indications for laparoscopic microwave coagulation
      therapy (LMCT) for hepatocellular carcinoma (HCC) have not yet been adequately
      evaluated. This study investigated the value of LMCT in the treatment of HCC.
      PATIENTS AND METHODS: Forty-three patients with liver cirrhosis (including five
      patients in Child Pugh grade C), with 56 HCC lesions, were enrolled in the study.
      When dynamic computed tomography (CT) showed a loss in HCC enhancement
      characteristics and a low concentration area after LMCT, a lesion was judged to
      have undergone complete necrosis. RESULTS: The rate of complete necrosis for
      lesions measuring 40 mm or less was significantly higher (P<0.01) than for those
      measuring 41 mm or more. The rate of complete necrosis for lesions located on the
      liver surface, excluding those located close to the gallbladder or in contact
      with the diaphragm, was also significantly higher (P<0.01) than for those
      situated deep within the liver. The outcome for lesions of 40 mm or less was
      favorable. Intra-abdominal hemorrhage occurred in two patients, pneumothorax in
      three, and hepatic infarction in one, all associated with LMCT. However, these
      patients did not suffer any sequelae of clinical significance. CONCLUSIONS: This
      study suggests that there is a strong indication for LMCT for HCCs measuring 40
      mm or less in diameter and those located on the liver surface even if they are as
      large as 50 mm, but not for those located close to the gallbladder or in contact
      with the diaphragm. LMCT appears to be applicable in patients with impaired liver
      function.

PMID- 10935788
TI  - Unrecognizable intramucosal spread of diffuse-type mucosal gastric carcinomas of
      less than 20 mm in size.
AB  - BACKGROUND: Diffuse-type intramucosal gastric carcinomas sometimes spread within
      the mucosa beyond their macroscopic margins, often causing positive resection
      margins upon local resections such as endoscopic mucosal resection. PATIENTS AND
      METHODS: A consecutive series of 34 patients with solitary, small (less than 20
      mm in diameter macroscopically), and macroscopically well demarcated diffuse-type
      mucosal carcinomas, who were treated with gastrectomy followed by detailed
      pathological examination, were included in the present study. Unrecognizable
      intramucosal spread is defined as an area of cancer which is indistinguishable
      macroscopically from its peripheral noncancerous area, and covered by normal
      epithelium with neither morphologic nor color changes. We examined the extent of
      unrecognizable intramucosal spread, measuring the maximum distances between
      macroscopic and microscopic margins on the sections, and investigated its
      relationship with four factors: location of the lesion, macroscopic size,
      histologic ulcer formation, and degree of atrophy of the background mucosa.
      RESULTS: The maximum distance between macroscopic and microscopic margins was
      significantly larger (maximum 10 mm) in the background mucosas with marked
      atrophy than in those with little or no atrophy. No other factors, including
      location, macroscopic size and ulcer formation, correlated with it. CONCLUSION:
      We should pay particular attention to unrecognizable intramucosal spread,
      especially in markedly atrophied mucosa, when treating small diffuse-type mucosal
      gastric cancer by local resections such as endoscopic mucosal resection. In
      addition, because of unrecognizable intramucosal spread, a surgical incision
      margin of at least 10 mm from the macroscopic margin is indicated.

PMID- 10935789
TI  - Shape-memory alloy loop snare for endoscopic photodynamic therapy of early
      gastric cancer.
AB  - BACKGROUND AND STUDY AIMS: Photodynamic therapy (PDT) has proved effective in the
      treatment of gastric cancer, but there is room for improvement. To achieve the
      technical goal of carrying out endoscopic PDT, endoscopists need to determine the
      precise area for laser irradiation at adequate dosages. This report describes the
      use of a shapememory alloy (SMA) loop snare as a useful tool in endoscopic PDT.
      PATIENTS AND METHODS: Eleven patients with biopsy-proved early gastric cancer
      were treated with endoscopic PDT after intravenous injection of Photofrin II (2
      mg/kg b.w.). Five patients underwent PDT using the SMA loop snare, and six
      underwent PDT without the use of the device. Cancer lesions smaller than 2 cm in
      diameter were irradiated with an excimer-dye laser (4 mJ, 80 Hz, 630 nm) for 20
      min. RESULTS: All five patients (100%) treated with PDT using the SMA loop snare,
      and four of the six patients (67%) treated with PDT without use of the SMA loop
      snare, showed complete remission. CONCLUSIONS: The SMA loop snare routinely forms
      a circle 2 cm in diameter, covering an area of 3.14 cm2, and makes it possible to
      mark and calculate the precise area of cancerous lesions for irradiation at
      appropriate dosages. The findings of this study suggest that the SMA loop snare
      is an effective tool for PDT in early gastric cancer.

PMID- 10935790
TI  - Gastric mucosal surface in cirrhosis evaluated by magnifying endoscopy and
      scanning electronic microscopy.
AB  - BACKGROUND AND STUDY AIMS: Gastric mucosa may have several tiny patterns in
      portal hypertension. In this prospective study, we used magnifying endoscopy and
      scanning electron microscopy (SEM) to better characterize the morphology of
      gastric mucosa in patients with cirrhosis, and we evaluated the diagnostic
      accuracy of magnifying endoscopy. PATIENTS AND METHODS: Videotapes of gastric
      mucosal patterns from 39 cirrhotic patients and 20 control patients were blindly
      evaluated by the same observer using magnifying endoscopy (magnification x 25)
      and conventional endoscopy. SEM was performed in 12 other patients. The basic
      anatomical entities of the gastric architecture on conventional endoscopy were
      the gastric area in control patients and the mosaic pattern in patients with
      cirrhosis. RESULTS: With regard to the prevalence of endoscopic patterns in the
      antrum, the mosaic pattern was more frequent in cirrhotic patients. In the body,
      the mosaic pattern, white spots, and red marks were significantly more frequent
      in cirrhotic patients, whereas gastric areas were more frequent in control
      patients. Concerning the contributions of the techniques, significantly more
      gastric areas were identified by magnifying endoscopy than by conventional
      endoscopy. However, in multivariate analysis, only conventional endoscopy with
      esophageal varices had significant independent diagnostic accuracy for cirrhosis,
      and magnifying endoscopy of mucosal signs did not add any significant
      information. SEM did not improve discrimination between control and cirrhotic
      patients. CONCLUSIONS: Magnifying endoscopy provides more details of the mucosa,
      thus improving the delineation of gastric mucosal morphology. However, magnifying
      endoscopy has little clinical value in cirrhosis since it does not improve on the
      accuracy of conventional endoscopy for the diagnosis of cirrhosis.

PMID- 10935791
TI  - Volume measurement using tissue characterization of three-dimensional endoscopic
      ultrasonographic images.
AB  - BACKGROUND AND STUDY AIMS: Although it is time-consuming to measure the volume of
      lesions using three-dimensional endoscopic ultrasonography (3D-EUS), the
      technique is suitable for tissue characterization, as it allows images of
      multiple areas to be obtained simultaneously in uniform conditions. The present
      study tested automatic volume measurement using tissue characterization based on
      3D-EUS. MATERIALS AND METHODS: Nine polygonal sections of resected spleen (volume
      0.66 +/- 0.19 cm3) were immersed in water, and 40 radial 3D-EUS images were
      obtained. For tissue characterization, the methods of co-occurrence matrix and
      gray-level difference and discriminant analysis were used. Each spleen section
      was also measured using 3D-EUS. The volume of tissue identified as spleen using
      tissue characterization and the volume calculated on the basis of the 3D-EUS
      images were both compared with the actual volume measured beforehand.
      Measurements using tissue characterization and 3D-EUS were carried out for every
      third image. In three clinical cases of cancer the volume of the lesion was
      measured using tissue characterization and 3D-EUS. RESULTS: The mean volume of
      the nine splenic sections estimated using tissue characterization was 1.2 +/-
      0.41 cm3 (mean +/- SD), while the mean volume estimated with 3D-EUS imaging was
      1.1 +/- 0.30 cm3 (mean +/- SD). The volumes measured using tissue
      characterization were on average 13% larger than those obtained with 3D-EUS.
      Linear regression analysis showed a high degree of correlation between the two
      sets of measurements (r=0.97, P<0.00005), and also showed a high correlation
      between the volumes obtained using tissue characterization and the actual volume
      (r=0.93, P<0.0005). However, the volumes calculated using 3D-EUS images were
      larger than the actual volume (61% on average), and the volumes estimated using
      tissue characterization were also greater than the actual volume. The
      overestimation reflected the fact that measurement was only carried out in every
      third 3D-EUS image. In the clinical cases, the mean value for "true" tumor tissue
      as determined on EUS imaging represented 73% of the volume interpreted as cancer
      using tissue characterization. CONCLUSIONS: There was a good correlation between
      the volume measured with 3D-EUS and the volume obtained using tissue
      characterization. The tissue characterization volumes were only relatively
      slightly larger than the volumes measured using 3D-EUS, suggesting that there may
      be some promise for this application of tissue characterization.

PMID- 10935792
TI  - Endoscopic ultrasonographic study of the azygos vein before and after endoscopic
      obliteration of esophagogastric varices by injection sclerotherapy.
AB  - BACKGROUND AND STUDY AIMS: The azygos vein plays an important role as a drainage
      system for the superior portosystemic collateral circulation in portal
      hypertensive patients. Endoscopic ultrasonography (EUS) and Doppler EUS allow the
      performance of hemodynamic studies of the azygos vein. In this study, we observed
      the changes in the azygos vein which occur with variceal obliteration by
      endoscopic injection sclerotherapy (EIS). PATIENTS AND METHODS: We recruited
      patients with portal hypertension and bleeding varices who were not on portal
      pressure-lowering agents and who were scheduled for the EIS program. EUS was
      performed in these patients to study the azygos vein at the start of EIS. The
      azygos vein diameter, maximal velocity (Vmax), and blood flow volume index (BFVI)
      were measured. After variceal obliteration and within 1 week, another EUS study
      of the azygos vein was carried out. RESULTS: Out of 40 patients recruited into
      the study variceal obliteration and EUS assessment of the azygos vein, within 1
      week of obliteration, was achieved in 33. We noticed a significant increase in
      azygos vein diameter (P<0.001) and BFVI (P=0.001) following variceal
      obliteration. No significant change was observed in Vmax (P>0.05). In one
      patient, marked caliber irregularities were observed in the azygos vein after
      variceal obliteration. CONCLUSIONS: Using EUS and Doppler EUS, hemodynamic
      studies of the azygos vein blood flow can be performed, allowing the monitoring
      of the effects of EIS and variceal obliteration on the superior portosystemic
      collateral circulation. The clinical significance of the observed changes in
      azygos blood flow that occur with variceal obliteration should be investigated in
      further studies and correlated with short-term and long-term outcome.

PMID- 10935793
TI  - Prediction of the clinical course of Behcet's colitis according to macroscopic
      classification by colonoscopy.
AB  - BACKGROUND AND STUDY AIMS: The lesions in Behcet's colitis show aphthoid or
      punched-out ulceration, but the macroscopic types of lesion found have not been
      defined. To predict the clinical outcome in patients with Behcet's colitis
      according to the colonoscopic findings, we classified the characteristic colonic
      ulcers, evaluated the efficacy of medical treatment on colonoscopic lesions, and
      calculated the operation rates and recurrence rates relative to the macroscopic
      types. PATIENTS AND METHODS: The medical records and colonoscopic photographs of
      50 patients with Behcet's colitis were reviewed. The colonic lesions were
      examined by colonoscopy in patients with Behcet's disease and gastrointestinal
      symptoms. The colonoscopic findings were categorized into three types of
      ulceration: volcano-like, geographic, and aphthous. The efficacy of medical
      treatment was assessed by follow-up colonoscopy or double-contrast barium enema
      four to eight weeks after treatment, and recurrence of the lesions was evaluated
      during the follow-up periods. Cumulative surgery rates were obtained using the
      Kaplan-Meier method. RESULTS: The macroscopic classification of colonic ulcers
      identified 25 of 50 patients (50%) with volcano-type lesions, 11 (22%) with the
      geographic type, and 14 (28%) with the aphthous type. The rates of complete
      remission after medical treatment and surgery, respectively, were six of 25 (24%)
      and 13 of 25 (52%) with volcano-type ulcerations; eight of 11 (73%) and one of 11
      (9%) with the geographic type; and nine of 14 (64%) and two of 14 (14%) with the
      aphthous type. The endoscopic and clinical recurrence rates were nine of 19 (47%)
      in volcano-type ulcerations, one of nine (11%) in the geographic type, and one of
      11 (9%) in the aphthous type. CONCLUSION: Volcano-type ulcerations in Behcet's
      colitis showed a less favorable response to medical treatment, a more frequent
      requirement for surgery, and more frequent recurrences than the geographic and
      aphthous types of ulcerations.

PMID- 10935794
TI  - Endoscopic decompression procedure in acute obstructing colorectal cancer.
AB  - BACKGROUND AND STUDY AIMS: In the treatment of acute obstructing colorectal
      cancer, a nasoenteric ileus tube is not capable of providing sufficient
      decompression of the enlarged intestine immediately, and it may cause the
      patients throat pain. We therefore assessed the effectiveness of an endoscopic
      decompression procedure using a transanal ileus tube for acute obstructing
      colorectal cancer. PATIENTS AND METHODS: Five patients (five women, mean age 62)
      with colorectal cancer ileus underwent endoscopic decompression procedures
      between July 1994 and March 1999. The stricture was first negotiated using a
      guide wire 300 cm in length, and was then dilated using 8 Fr and 26 Fr dilating
      catheters. Immediately after a transanal ileus tube 120 cm in length with an
      outside diameter of 22 Fr was inserted, the intestinal tract was cleaned.
      RESULTS: No leakage from a colorectal anastomosis occurred during this endoscopic
      decompression procedure. Immediately after insertion of a decompression procedure
      tube, radical surgery could be performed after adequate preoperative examination
      and colorectal preparation. CONCLUSIONS: This procedure may be helpful in
      allowing immediate preoperative examination and scheduling of a radical operation
      for acute obstructing colorectal disease.

PMID- 10935795
TI  - Local ablative therapy for hepatocellular carcinoma.

PMID- 10935796
TI  - A 68-year-old man with two small colon polyps.

PMID- 10935797
TI  - Endoscopic observation of squamous metaplasia of the stomach: a report of two
      cases.
AB  - Squamous metaplasia of the stomach is a rare clinical entity that occurs during
      healing of gastric ulcers or chronic inflammation. We have treated two patients
      with this condition, which has only occasionally been observed endoscopically.
      The first was a 60-year-old woman who initially presented with multiple gastric
      ulcers. Two months after treatment, a white patch about 4 cm in diameter was
      found in the lesser curvature of the cardiac region of stomach. The second
      patient was a 65-year-old woman, who also developed a white patch in the same
      region. Two months later, a small ulcer and inflamed mucosa were seen near the
      lesion. The white areas in both patients were stained with Lugol's iodine
      solution, and biopsy specimens confirmed squamous epithelium. The squamous
      metaplasia was observed as a white mucosal area in the stomach, and the
      metaplastic area stained positively with Lugol's iodine solution.

PMID- 10935798
TI  - Treatment of infected pancreatic pseudocysts by endoscopic ultrasonography-guided
      cystogastrostomy.
AB  - It has been appreciated for a long time that surgery is the treatment of choice
      for symptomatic, and especially infected, pancreatic pseudocysts. This paradigm
      is now being challenged by endoscopic cystoenterostomy and cystogastrostomy,
      which have both been employed with success in selected patients. We present three
      cases in which infected pancreatic pseudocysts resolved following endoscopic
      cystogastrostomy guided by endoscopic ultrasonography (EUS).

PMID- 10935799
TI  - A case of ileocolic intussusception from renal cell carcinoma.
AB  - We report a case of ileal metastasis of renal cell carcinoma (RCC) in a 58-year
      old male. The patient had a history of radical nephrectomy for a right RCC, and 2
      years later underwent bilateral partial pneumonectomy for metastatic disease of
      the lung. A period of 1 year after the partial pneumonectomy, he developed bloody
      stools. Colonoscopy revealed an ileocolic intussusception caused by a polypoid
      tumor in the ileum, and the tumor was observed to be protruding into the
      ascending colon. The histological features of the tumor biopsy specimen confirmed
      the diagnosis of metastatic RCC. Metastasis of RCC in the small bowel is a rare
      disease clinically. To our knowledge, this is the first reported case with ileal
      metastasis of RCC, which has been definitively diagnosed by colonoscopy.

PMID- 10935800
TI  - Upper gastrointestinal hemorrhage secondary to erosion of a biliary Wallstent in
      a woman with pancreatic cancer.
AB  - A 77-year-old patient with unresectable pancreatic adenocarcinoma sustained a
      life-threatening, upper gastrointestinal hemorrhage 1 month after placement of a
      biliary Wallstent. Radiographic and endoscopic studies revealed a choledocho
      arterio-enteric fistula caused by erosion of the stent through the posterior
      duodenal wall. The patient was treated successfully with arterial embolization.
      This represents an unusual case of arterial bleeding with choledocho-arterio
      enteric fistulization into the duodenum subsequent to biliary stent erosion.

PMID- 10935801
TI  - Primary or secondary sclerosing cholangitis?

PMID- 10935802
TI  - Difficult duodenum during endoscopic retrograde cholangiopancreatography.

PMID- 10935803
TI  - Nonoperative management of biliary stent-induced duodenal perforation.

PMID- 10935804
TI  - Esophageal perforation: is minimally invasive treatment possible?

PMID- 10935805
TI  - Appendicitis following endoscopic polypectomy.

PMID- 10935806
TI  - A simple and well-tolerated method for sampling gallbladder bile.

PMID- 10935807
TI  - Images in focus. A strange resident in the colon.

PMID- 10935808
TI  - Images in focus. Severe colonic damage associated with non-steroidal anti
      inflammatory drug ingestion.

PMID- 10935810
TI  - A cost-benefit analysis of initial burn cultures in the management of acute
      burns.
AB  - It is common practice to obtain cultures in the first 24 hours after burn
      injuries. However, little evidence exists that these tests change clinical
      practice or clinical outcome. We conducted a retrospective chart review to
      determine how often the results of wound and other cultures lead to changes in
      the clinical treatment of patients. A total of 598 charts were reviewed. Four
      hundred forty-seven patients had a length of stay in the hospital of 1 day or
      less and were primarily treated in the emergency department and then discharged
      from the hospital. Wound cultures were obtained for 42 (10%) of these patients.
      Thirty cultures (71%) had no significant growth. Twelve cultures (29%) grew mixed
      common skin flora. No patients in this group were "pan-cultured." No patients in
      this group required antibiotic treatment on the basis of culture results. A total
      of 151 patients were admitted to the burn center, with an average length of stay
      of 3.9 days (range, 2-125 days). In this group, 45 patients (30%) had wound
      cultures and 24 patients (16%) were pan-cultured in the first 24 hours after
      admission to the hospital. Enterococcus species grew in the initial wound culture
      of 1 patient, and the patient was treated with antibiotics. Antibiotics were not
      ordered for any other patients on the basis of cultures. The collection of
      routine cultures during the first 24 hours after admission to the hospital is not
      cost-effective and rarely alters or provides therapeutic direction. An estimated
      $14,000 per year decrease in charges could be achieved by the elimination of
      cultures taken during the first 24 hours of admission to the hospital.

PMID- 10935809
TI  - Controlled clinical study of deep partial-thickness burns treated with frozen
      cultured human allogeneic epidermal sheets.
AB  - Numerous studies, many uncontrolled, have suggested that the application of
      freshly prepared human allogeneic epidermal cultures promotes faster re
      epithelialization of skin donor sites and deep partial-thickness burns. We
      describe the results of a study of deep partial-thickness burns treated with such
      cultures preserved in the frozen state. The study was controlled, side-by-side
      comparative, and randomized. Nine patients with deep partial-thickness burns and
      2 patients with superficial partial-thickness burns were treated with the frozen
      cultures, with the use of adjacent wounds covered with petrolatum-coated gauze
      (Jelonet, Smith & Nephew Inc, Largo, Fla) as control wounds. The results showed
      that for the 2 superficial partial-thickness burns, the frozen cultures reduced
      healing time by 44%. For 5 of the patients with deep partial-thickness burns, the
      wounds treated with frozen cultures healed in a mean time of 5.6 days, whereas
      the control wounds healed in 12.2 days. More importantly, for the 4 other
      patients with deep partial-thickness burns, the wounds treated with the frozen
      cultures underwent complete re-epithelialization in a mean time of 4.2 days, but
      the control wounds were partially or mostly unhealed at up to 14 days. The
      results show that the frozen cultures not only accelerate the re
      epithelialization of deep and superficial partial-thickness burns but also make
      it possible to heal such wounds that otherwise would not heal.

PMID- 10935811
TI  - Successful preservation of human skin by vitrification.
AB  - The vitrification technique was applied to the preservation of human skin. This
      technique was simple, and no expensive equipment was needed. Split-thickness
      human skins from 8 patients were immersed in vitrification solution for 10
      minutes at room temperature, immediately plunged into a liquid nitrogen tank, and
      cryopreserved for 3 weeks. The vitrification solution consisted of 40% ethylene
      glycol (vol/vol) and phosphate buffered saline solution that contained 30% Ficoll
      70 (vol/vol; Wako Junyaku, Co, Tokyo, Japan) and 0.5 mol/L sucrose. The viability
      of vitrified and cryopreserved skin was evaluated with the trypan blue dye
      exclusion test, the methyl-thiazoldiphenyl-tetrazolium (MTT) colorimetric assay,
      and a culture test of the keratinocytes obtained from vitrified skin. The results
      of the trypan blue dye exclusion test showed 87.4% of viable cells, and MTT
      developed an average 0.817 absorbance. When vitrified skin was compared with 4
      degrees C refrigerated skins after 3 weeks of storage, the difference of
      viability was significant both on the trypan blue dye exclusion test (P < .05)
      and on the MTT assay (P < .01). However, there was no significant difference in
      the viability of vitrified skins compared with fresh skin. Furthermore,
      keratinocytes from vitrified skin grew uneventfully in culture test. We used
      these vitrified skin allografts for patients with flame burns and electric burns.
      These allografts took well in both cases and promoted wound healing. We concluded
      that the vitrification method for skin preservation is simple and reliable, and
      this method could contribute to skin banking.

PMID- 10935812
TI  - The management of self-inflicted burn injuries and disruptive behavior for
      patients with borderline personality disorder.
AB  - One of the greatest behavioral and ethical challenges faced by a burn team is the
      treatment of a patient whose burn injury is the result of parasuicidal behavior.
      Parasuicidal behavior is defined as intentional self-injurious behavior that,
      although not fatal, may result in tissue damage or risk of death. There are a
      number of reasons, usually psychiatric, that patients engage in parasuicidal
      behavior; however, our contention is that the majority of these patients have a
      Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Axis II
      diagnosis of borderline personality disorder. We describe the nature of
      borderline personality disorder and how it leads to disruptive behavior,
      including self-harm behavior, on the burn unit, We also argue that if staff
      members fail to recognize the borderline personality disorder diagnosis, it will
      lead to responses from staff that can heighten disruptive behavior. We present a
      series of recommendations for treating such patients with burns and an
      illustrative case report.

PMID- 10935813
TI  - Describing and predicting the nature of procedural pain after thermal injuries:
      implications for research.
AB  - A prerequisite for studying and treating burn-related pain is the establishment
      of a good understanding of the nature of burn-related pain. However, in most
      investigations of pain, researchers have failed to examine pain over time or to
      create summary scores that capture differences in the nature of the pain
      experiences of individual patients. For 10 consecutive days, 47 patients treated
      for burn injuries reported on three aspects of procedural pain: worst pain,
      sensory pain, and affective pain. Three summary pain scores were constructed for
      each pain dimension: average pain, variability in pain, and linear change in
      pain. The authors found considerable variability in pain reports from the same
      patient and from different patients. Analyses indicated that pain reports
      decreased over time and that patients who had more trait anxiety reported more
      pain. Patients with larger burn injuries tended to report more affective pain and
      tended to have a pattern of high and low pain reports that differed from patients
      with less severe burn injuries. These findings suggest that adequate assessment
      of burn pain must occur frequently over the course of a single day, as well as
      for the duration of each patient's care.

PMID- 10935814
TI  - Occupation-related burn injuries.
AB  - Unlike household burn injuries, the characteristics of burn injuries in the
      workplace have not been well described. In an effort to understand the causes and
      effects of occupation-related burn injuries and to aid in prevention, we sought
      to describe work-related burn injuries by frequency, burn type, age of the
      patients, body parts burned, and occupation of the patients. This was a
      statewide, cross-sectional study of all burns that occurred in the workplace
      during 1994. Data on fatal injuries were obtained from the National Census of
      Fatal Occupational Injuries. Survey data from the North Carolina Department of
      Labor were used for nonfatal injuries. Burns caused 34 deaths (15.3%) and 1720
      injuries in the workplace in 1994. Of the nonfatal injuries, 1363 (79.2%) were
      caused by exposure to caustic substances or hot objects or substances. The head
      and upper extremities were the most frequently injured body parts (936 injuries;
      57.6%). The average age of those burned was 30.7 years; most of the patients
      ranged from 25 to 35 years old. High-risk occupations included vehicle and
      equipment cleaners, food service personnel, and millwrights (11.3%, 5.3%, and
      5.2% of burn injuries, respectively). Unlike the flame burns that occur in homes,
      exposure to caustics and hot objects and substances caused the majority of on-the
      job burn injuries. Protective gear for the head and upper extremities may prevent
      a significant number of burns. Education and prevention programs may best be
      directed at workers with high-risk occupations and workers in the 25- to 35-year
      age range.

PMID- 10935815
TI  - Determination of burn depth with noncontact ultrasonography.
AB  - Early excision and grafting is the current treatment of choice for deep dermal
      and full-thickness burn wounds that will not heal spontaneously within 3 weeks.
      The time needed for the burn wound to heal is estimated with clinical assessment
      of the burn depth; this is often an inaccurate method. Therefore we have
      developed a new and unique noncontact ultrasonographic method to estimate burn
      depth. This study was designed to determine the practical utility and accuracy of
      noncontact ultrasonography for the assessment of burn depth. Seventy-eight burn
      sites and 42 normal skin sites (control sites) of 15 patients (age, 18-63 years)
      with burns of 2% to 35% total body surface area were evaluated. The burn sites
      were scanned with a prototype noncontact ultrasonographic system 1 and 3 days
      after the burn injuries. The probe was held 1 inch from the skin, and the time
      spent on each site was approximately 5 minutes. The ultrasonographic results were
      interpreted by an investigator who was blinded to the clinical findings. Clinical
      assessment of the burn wounds was made on the same days by 2 experienced
      physicians who were blinded to the results of the ultrasonography. The
      investigators were asked to categorize the burn wounds into those that would heal
      within 3 weeks and those that would not. With this method, we were able to
      visualize the epidermis, dermis, and dermal-fat interface in normal skin. The
      destruction of the dermal-fat interface was interpreted as a deep burn, which
      would not heal within 3 weeks. The overall accuracy of the noncontact
      ultrasonography in the prediction of which burn wounds would heal within 3 weeks
      was 96%. The results of this study show that noncontact ultrasonography will
      allow for the rapid evaluation of burn depth with high accuracy, without
      contacting the patient, and without causing pain or discomfort.

PMID- 10935816
TI  - The role of autopsy on patients with burns.
AB  - Burn center verification requires the use of autopsy as one method of quality
      assurance in a burn center. Because of the decreasing rates of autopsies
      worldwide and improved diagnostic accuracy in our critical care units, we tested
      the hypothesis that autopsy diagnosis would not alter our clinical diagnosis. A
      chart review of all deaths (N = 94) that occurred during a 6-year period (1989
      1994) was performed. The clinical diagnoses from the hospital charts and autopsy
      reports for the patients were reviewed, and diagnostic discrepancies were
      classified as class I or class II errors. Class I diagnostic errors might have
      altered the clinical outcome. Class II errors were attributable to the burn
      injuries but were believed to have had little impact on the clinical outcome. The
      overall autopsy rate was 93.6% (n = 88). Clinical diagnostic errors were found in
      16 (18%) of 88 patients. Five class I errors were found in 4 patients (4.5%), and
      15 class II errors were found in 13 patients (14.7%). Although the rate of
      potentially serious errors was low (only 4.5% of the patients in this study)
      postmortem examinations revealed clinical diagnostic errors. The results of this
      study support the continued use of autopsies as a means of quality assurance,
      despite our ability to closely monitor our critically ill patients with burns.

PMID- 10935817
TI  - Skin lipopolysaccharide-binding protein and IL-1beta production after thermal
      injury.
AB  - In response to a burn injury, skin can have an inflammatory response
      characterized by the production of inflammatory cytokines, recruitment of immune
      cells, containment of invading organisms, and clearance of noxious substances
      from the wound. Lipopolysaccharide-binding protein (LBP) is a molecule that is
      capable of coordinating all 4 functions; we previously found evidence that
      suggested that LBP is produced within surgical wounds. Because of the central
      role of LBP in the response to bacterial infection, as well as in the high rate
      of infection after burn injuries, we sought to determine whether a thermal injury
      could affect wound LBP production and thereby affect host responses against
      bacterial infection. Rats were given either a burn or a sham burn and were killed
      24, 48, and 72 hours after the injuries. Wound specimens were assayed for
      bacterial counts and for the presence of LBP, messenger (m)RNA, and interleukin
      (IL)-1beta mRNA. Wound LBP mRNA was significantly upregulated at 24 hours in the
      group with burn injuries (P < .05; burn vs sham burn); this was followed by
      decreases at 48 and 72 hours. Immunohistochemistry showed LBP protein in the
      epidermis of animals with burns. Bacterial counts increased in the group with
      burn injuries (P < .05; burn vs sham burn) and continued to rise for 72 hours. IL
      1beta mRNA levels were elevated at all time points in the group with burn
      injuries (P < .05). These results suggest an inverse correlation between burn
      wound LBP expression and bacterial wound counts. This failure to maintain local
      LBP production after severe thermal injury despite localized inflammation shown
      by high IL-1beta levels may predispose local wounds to bacterial invasion.

PMID- 10935818
TI  - FDA regulation of human tissue: implications for skin banks and burn centers.

PMID- 10935820
TI  - Computerized registry recording of psychiatric disorders of pediatric patients
      with burns.

PMID- 10935819
TI  - Comparison of measures of physiologic stress during treadmill exercise in a
      patient with 20% lower extremity burn injuries and healthy matched and nonmatched
      individuals.
AB  - Patients with burn injuries are referred for rehabilitation within days after the
      injuries to encourage early ambulation and functional training. Many of these
      patients are hypermetabolic at rest. Metabolic demands of activity are added to
      the already hypermetabolic state and elevate total energy requirements and some
      physiologic measures. Reports on the physiologic stress imposed by therapeutic
      activities for patients with burn injuries are limited to low levels of metabolic
      demand (< or =2 metabolic equivalents [METS]). The degree of stress imposed by
      functional activities such as ambulation (3 METS) and stair climbing (5 METS) is
      not known for adults with burn injuries. The purpose of this study was to report
      the clinical measures of myocardial and physiologic stress in a patient with 20%
      lower extremity total body surface area burns during an exercise challenge
      equivalent to stair climbing. Physiologic measures were assessed before and
      during a treadmill activity (5 METS) for a 40-year-old obese man 3 weeks after he
      had lower extremity burn injuries. These measures were compared with mean values
      for 62 healthy counterparts and 6 healthy subjects matched for age, gender, and
      fitness level. Heart rate, systolic blood pressure, rate pressure product, and
      the rating of perceived exertion for the patient with burn injuries were higher
      at baseline and during exercise than the mean values for the 62 healthy
      individuals and the 6 matched subjects. The steady state exercise values for
      heart rate, systolic blood pressure, rate pressure product, and rating of
      perceived exertion at 6 minutes were 189 beats per minute, 190 mm Hg, 3591, and
      17, respectively, for the patient with burn injuries and were 111.3 beats per
      minute, 149 mm Hg, 1680, and 11.7, respectively, for the 6 matched subjects.
      Ventilation during exercise also increased for the patient with burn injuries
      more than for the matched subjects (3/4 vs 1/4). Pain experienced by the patient
      with burn injuries decreased with activity (9.8 vs 7.3 on a 15-cm scale).
      Treadmill walking produced near maximal responses for most physiologic measures
      for this patient who was hypermetabolic at rest. We provided normative data to
      assist therapists who work with patients with similar burn injuries.

PMID- 10935821
TI  - Energy deficits associated with nasogastric feeding in patients with burns.
AB  - This study was designed to identify whether significant energy deficits occur
      when feedings are (1) withheld perioperatively and (2) withheld because of
      gastric ileus. We studied patients with more than 20% total body surface area
      burns, who had survived at least one surgery, and who were intubated within 3
      days of admission. Energy needs and energy received from enteral feedings were
      summed across the period during which the patients underwent surgical procedures.
      The difference between energy needed and energy received was divided into that
      caused by feedings being withheld perioperatively and that caused by feedings
      being withheld because of a gastric ileus. Twenty-five patients (9 women and 16
      men) were included in the study. The total energy deficit was a mean of 15,969
      kcal (31.6% of 50,546 kcal needed); 58% of the energy deficit (9264 kcal of the
      15,969 kcal deficit) was caused by feedings being withheld perioperatively and
      42% of the energy deficit (6705 kcal of the 15,969 kcal deficit) was caused by
      feedings being withheld because of gastric ileus. The withholding of feedings
      perioperatively and because of gastric ileus were both significant contributors
      to energy deficits. Future studies are necessary to determine whether energy
      needs being more closely met would result in improved outcomes for these
      patients.

PMID- 10935822
TI  - Psychological principles of burn wound pain in children. I: theoretical
      framework.
AB  - Burn injuries and the care of burn injuries are punishing experiences for
      hospitalized children. Pain, novelty, and altered reinforcement schedules elicit
      instinctive escape and avoidance behaviors that complicate wound care. An
      understanding of the psychological principles that underlie these complex,
      complicating behaviors paves the way for effective cognitive and behavioral
      interventions. In this first article of a two-part series, we use the principles
      of classical conditioning, operant conditioning, and control coping to describe
      the developmentally normal emergence of avoidance behaviors that are incompatible
      with burn wound care. Then, using brief case examples, we outline how classical
      conditioning transforms neutral stimuli into anxiety-producing, fearful stimuli,
      how operant behaviors are intentionally or unintentionally reinforced, and how
      the umbrella of reduced control in the novel hospital environment makes coping
      difficult for children. We conclude by discussing obstacles to effective
      application of cognitive and behavioral strategies for the enhancement of control
      and of compliance with wound care.

PMID- 10935823
TI  - Safety and efficacy of TransCyte for the treatment of partial-thickness burns.

PMID- 10935824
TI  - The relationship between oxygen delivery and oxygen consumption during fluid
      resuscitation of burn-related shock.

PMID- 10935825
TI  - Appropriate discard volumes when drawing arterial blood for hematocrit
      determination.

PMID- 10935826
TI  - Appropriate discard volumes when drawing arterial blood for hematocrit
      determination.

PMID- 10935827
TI  - The complex clinical and genetic classification of inherited ataxias. I. Dominant
      ataxias.
AB  - The clinical classification of autosomal dominant cerebellar ataxias (ADCAs) is
      intricate due to the variable and unpredictable association of signs and symptoms
      of central nervous system (CNS) and peripheral nervous system (PNS) deterioration
      during the life of a patient. However, for many purposes, particularly patient
      management, clinical systematics is the most useful method for labelling
      patients; in some instances there is no basis for any more fundamental
      classification of phenotypes. On the other hand, recent molecular-genetic
      approaches to dominant ataxias have had a profound impact in nosology, diagnostic
      procedures and the management of patients, since they are based on the fact that
      all mendelian neurological diseases can be precisely classified according to the
      locus involved as well as the particular mutant allele at that locus. Therefore,
      a clinical and genetic classification of dominant ataxias is herewith proposed as
      the best nosographical choice. Clinical, neuropathological, genetic, and
      pathogenetic aspects of ADCAs are reviewed and discussed to help the clinical
      neurologist guide diagnostic procedures and manage ataxic patients.

PMID- 10935828
TI  - Clinical and genetic study of a family with spinocerebellar ataxia type 1 (SCA1)
      and beta-thalassemia.
AB  - We report a family affected by autosomal dominant ataxia, in which numerous
      members also showed microcytosis. Genetic analysis demonstrated a CAG expansion
      in the SCA1 locus in five members, while all subjects with microcytosis revealed
      a C-T substitution at codon 39 of the beta-globin gene. A pure cerebellar
      syndrome with prominent gait ataxia characterized the first stages of the
      neurological disease. The fully developed disease included additional clinical
      findings such as dysarthria and dysphagia, and instrumental signs of axonal
      involvement of the peripheral nerves. Ophthalmoplegia was not observed. The
      coexistence of hereditary spinocerebellar degeneration and erythropathies or
      hemoglobinopathies has been previously described. We discuss the possible
      linkages between these two pathologies.

PMID- 10935829
TI  - Stroke incidence and survival in three Sicilian municipalities. Sicilian Neuro
      Epidemiologic Study (SNES) Group.
AB  - We investigated the incidence of first-ever stroke in three Sicilian
      municipalities over the years 1984-1987. Case ascertainment involved two
      approaches: a door-to-door two-phase prevalence survey and a study of death
      certificates. Only first-ever strokes occurring within the study time interval
      were included, and diagnoses were based on specified criteria. We found 138
      subjects who had experienced a first stroke over 73 488 person-years; the average
      incidence rate (new cases per 1000 population per year) was 1.9 overall, 1.7 in
      men, and 2.1 in women. Incidence increased steeply with age and was similar in
      men and women. Incidence was similar in the three study municipalities. The
      overall case-fatality rate was 35% at 30 days and 22% at one week. Survival after
      stroke was similar in men and women but better in younger compared to older
      stroke patients. Comparisons with previous studies suggest the absence of major
      geographic variations in stroke incidence within Italy.

PMID- 10935830
TI  - Natural history of carpal tunnel syndrome according to the neurophysiological
      classification.
AB  - Although many studies on carpal tunnel syndrome (CTS) have been reported, few
      data on the natural history of CTS are available. Knowledge of the natural course
      of the disease has significant clinical and therapeutic value. We prospectively
      followed up 80 cases of untreated CTS. The evaluation was based on self
      administered questionnaires and on neurophysiological investigation. According to
      the neurophysiological classification, cases of CTS were divided into six groups
      on the basis of impairment severity: negative, minimal, mild, moderate, severe,
      and extreme. Disease worsening was inversely related to severity of nerve
      entrapment. On the contrary, improvement was proportionally related to nerve
      function impairment (except for extreme cases that never improved), and about one
      third of mild and moderate cases improved. Most minimally cases remained
      neurophysiologically unchanged. We hypothesize that in a good percentage of CTS
      cases, nerve impairment is self-limited. Our data suggest the utility of further
      studies on the natural course of this common disease.

PMID- 10935831
TI  - Reduced glutathione in amyotrophic lateral sclerosis: an open, crossover,
      randomized trial.
AB  - The present study set out to define the possible effect of reduced glutathione
      (GSH), the substrate of glutathione peroxidase (GSH-Px), a free radical
      inactivating enzyme, in amyotrophic lateral sclerosis (ALS). Thirty-two patients
      affected by definite ALS seen in our institution between August 1993 and July
      1994 were admitted to the study. The effect of GSH was studied in an open,
      crossover, randomized study. GSH was given at the dose of 600 mg each day
      intramuscularly for 12 weeks. The patients, taken sequentially, were randomly
      assigned to two groups. The first group received the drug while the second
      received only symptomatic therapies for 12 weeks. After a week of washout, the
      second group received GSH and the first only symptomatic therapies for 12 weeks.
      The rate of progression of the diseases was compared in the two groups. Clinical
      evaluation included manual test for muscle strength, Norris scale, bulbar scale,
      and forced vital capacity (FVC) percent. No significant difference was found in
      the progression of ALS in the two periods, although a slight slowing of the
      disease progression rate was found during the period of treatment, probably
      related to the open design of the study. Our data do not show any significant
      effect of reduced glutathione in modifying the progression of ALS.

PMID- 10935832
TI  - Long-term effects of boxing and judo-choking techniques on brain function.
AB  - Regional cerebral blood flow (rCBF) was measured by 133-xenon inhalation in 24
      amateur and 20 professional boxers, and in 10 judoka. Results were compared with
      those from age- and sex-matched healthy controls. Eighteen boxers (9 amateurs and
      9 professionals) and all judoka also underwent electroencephalography (EEG). Mean
      rCBF values did not differ between either amateur boxers orjudoka and controls,
      whereas in professional boxers rCBF was significantly (p<.001) reduced in the
      whole brain, especially in the frontocentral regions. Healthy subjects, judoka,
      and amateur boxers showed a similar distribution of global CBF (gCBF, the mean of
      32 probes) values, although 12.5% of amateurs had a significantly lower gCBF than
      controls. Among professional boxers, 25% showed a significantly low gCBF value;
      in the remaining 75%, gCBF was below the mean value of controls but did not reach
      statistical significance. Regional hypoperfusion, mainly in the frontocentral
      regions of both sides, was found in 35% of professional and in 29% of amateur
      boxers. A correlation between gCBF values and number of official matches was not
      found in boxers. EEG was normal in all judoka and amateur boxers, but it was
      abnormal in 3 professionals. This study shows the relevance of the
      neurophysiological assessment of athletes engaged in violent sports which can
      cause brain impairment. In fact, while professional boxers may show brain
      functional impairment in comparison to normal subjects, judoka do not. The lack
      of correlation between CBF values in boxers and the number of official matches
      points to the difficulty of taking into account variables, such as the number and
      the severity of matches during training.

PMID- 10935833
TI  - Feasibility in the clinical setting of perfusion brain SPECT imaging employing a
      brain-dedicated gamma camera and the conjugate gradients with modified matrix
      reconstruction method.
AB  - In the present study, we compared Tc-99m HMPAO single photon emission computed
      tomography (SPECT) brain images obtained using the conventional filtered
      backprojection (FBP) reconstruction method with the new reconstruction method of
      conjugate gradients with modified matrix (CGMM). The two methods were employed to
      generate SPECT images of a brain perfusion study in a 41-year-old patient who had
      suffered from multiple embolisation of the right hemisphere. Marked improvement
      in spatial resolution was achieved by CGMM reconstruction as compared to FBP
      reconstruction; this considerably helped in defining grey matter structures and
      low-uptake white-matter areas, both in the normal cerebral areas and in the
      hemisphere that had been affected by stroke. Although the relatively long time
      still required by the CGMM procedure might be considered as a significant
      drawback to date, with the increasing diffusion of the new computer facilities
      the CGMM method can be proposed as a valuable alternative to the standard FBP
      technique in order to better recognise cerebral areas with different tracer
      uptake.

PMID- 10935834
TI  - Isolated hypoglossal nerve palsy due to an anomalous vertebral artery course:
      report of two cases.
AB  - The authors report two patients with isolated unilateral tongue atrophy. Magnetic
      resonance imaging (MRI) of the brain stem and angio-MRI demonstrated a
      dolichovertebral artery with an abnormal course compressing the medulla oblongata
      at the emergence of the hypoglossal rootlets. The semeiological observation of a
      sectorial and not uniform distribution of atrophy in the half-affected tongue is
      discussed in relation to the lesional site.

PMID- 10935835
TI  - Tourettism as clinical presentation of Huntington's disease with onset in
      childhood.
AB  - Infantile Huntington's disease (HD) shows a wide clinical heterogeneity. Here we
      describe the case of a child affected by HD who showed unusual neurological
      features consistent with tourettism. The absence of family history and persisting
      normal magnetic resonance imaging (MRI) results long after the onset of symptoms
      delayed the diagnosis of the disease. An MRI exam performed 26 months after
      disease onset disclosed bilateral atrophy in the putamen, suggesting HD. The
      diagnosis was confirmed by genetic analysis. The present report underlines the
      need to consider HD in childhood cases of unusual and even unfamiliar progressive
      movement disorders.

PMID- 10935836
TI  - Pitfalls in using the ring finger test alone for the diagnosis of carpal tunnel
      syndrome.
AB  - Latency differences (>0.5 ms) of median and ulnar sensory action potentials (mSAP
      and uSAP) at the wrist evoked by ring finger stimulation are considered a
      sensitive and specific test for diagnosis of carpal tunnel syndrome (CTS). In
      this study, we aimed to assess the practical usefulness of the ring finger test
      (RFT) in routine electromyography (EMG) examinations. We investigated 2 series of
      patients: in the first prospective series we considered 300 hands affected by
      only mild CTS; in the second series we examined retrospectively the EMG charts of
      961 hands affected only by CTS but not selected for severity or duration of
      symptoms. In the first series we found pathological RFT scores in 87% of cases,
      and pathological RFT or mSAP latency results in 92%. In the second series,
      pathological RFT scores were found only in 55% of cases, while in 20% where mSAP
      failed, a volume conducted uSAP had been erroneously interpreted as arising from
      the median nerve. RFT sensitivity tested in routine EMG examinations of
      unselected hands affected by CTS drops considerably. Fingers innervated by one
      only nerve, such as the index and the little fingers, must also be investigated
      to increase the diagnostic value of RFT.

PMID- 10935837
TI  - Pharmacological and behavioral treatment of pediatric migraine and tension-type
      headache.
AB  - The problem concerning the treatment of pediatric headache has been the object of
      several recent reports. Some of the same medications used to treat adult headache
      problems are also utilized with children but usually at smaller dosages and in
      different combinations. The recent application of behavioral approaches, in
      particular biofeedback, for treatment of children's headaches has been an
      effective alternative to drugs without the problematic and dangerous side effects
      of pharmacological treatments. The purpose of this review is to give some
      indications about the most common pharmacological therapies for migraine and
      tension-type headache in children, and also to discuss the use of behavioral
      therapies, in particular biofeedback, as excellent alternatives to drugs.

PMID- 10935838
TI  - Occurrence of thyroid autoimmunity in relapsing remitting multiple sclerosis
      patients undergoing interferon-beta treatment.
AB  - We analyzed the titer of antithyroid autoantibodies (Abs) and thyroid function in
      17 multiple sclerosis (MS) patients undergoing interferon-beta (IFN-beta)
      treatment and in 40 MS control patients. Basal evaluation revealed normal thyroid
      function in all patients. Abs were detected in 5 IFN-beta-treated patients (29%)
      and in 4 MS control patients (10%). Our results indicate that IFN-beta treatment
      may lead to thyroid autoimmunity. We therefore recommend periodic evaluations of
      antithyroid Abs and thyroid functionality in IFN-beta-treated MS patients.

PMID- 10935839
TI  - Predictive testing for Huntington's disease: ten years' experience in two Italian
      centres.
AB  - Pre-symptomatic testing for Huntington's disease (HD) has been available as a
      clinical service in the medical centres of Rome and Genoa since December 1987,
      initially by DNA-linkage and since mid-1993 by direct mutation analysis. A
      multidisciplinary approach and a protocol which follows the Ethical Issue Policy
      Statement on Huntington's Disease Molecular Genetics Predictive Test has been
      used. In the period under study, 332 subjects requested the test, 288 were
      enrolled in the protocol and nearly half of these completed it. One hundred and
      forty-eight people withdrew from the testing procedure for various reasons but
      most frequently due to a more realistic evaluation of all possible consequences
      of test results, induced by psychological counselling. Therefore, 140 people
      completed the test. The overall gene-carrier/non-carrier ratio was 0.46:1. None
      of the identified gene carriers had catastrophic reactions such as suicide,
      suicide attempts or major psychiatric disorders. All appear to have had a similar
      pattern of reactions to an adverse result and none expressed regret for
      undergoing the test. In conclusion, presymptomatic testing for HD can be
      considered a safe procedure without adverse consequences when framed in an
      integrated protocol at qualified genetic centres.

PMID- 10935840
TI  - Positive correlation of CTG expansion and pharyngoesophageal alterations in
      myotonic dystrophy patients.
AB  - Alteration of the pharyngoesophageal musculature is a common finding in patients
      with myotonic dystrophy (MD), regardless of the presence of dysphagia. The aim of
      the present study was to determine whether a specific pattern of swallowing
      abnormalities could be identified in MD patients, and the possible correlation
      with the size of CTG repeats. Fifteen MD patients, 8 of whom were asymptomatic
      for dysphagia, underwent a videofluoroscopic study of swallowing. Alterations of
      the pharyngoesophageal phase of swallowing were detected in 12 of 15 patients, 6
      without clinical evidence of dysphagia. Incomplete relaxation of the upper
      esophageal sphincter (UES) and esophageal hypotonia were the most common
      alterations. We found a significant correlation between the number of
      radiological alterations and the size of CTG repeats. A typical radiological
      pattern of swallowing has also been identified. The role of videofluoroscopy in
      evaluation of MD patients is briefly discussed.

PMID- 10935841
TI  - Isolated neuritis of the sciatic nerve in a case of Lyme disease.
AB  - Lyme disease is an infectious disease caused by the spirochete Borrelia
      burgdorferi. The course of the disease is divided into three stages, the second
      of which may include various types of peripheral nervous system disturbances. We
      report the case of a patient with persistent deficits caused by the prevalent
      involvement of the sciatic nerve, confirmed by electrophysiological and
      neuropathological findings. The most significant bioptic results were axonal
      degeneration and perivascular inflammation. Damage to a single peripheral nerve
      as the dominant clinical expression during the course of Lyme disease is an
      unusual finding that has been rarely described in the literature.

PMID- 10935842
TI  - Reversible combined cognitive impairment and severe polyneuropathy resulting from
      primary hyperparathyroidism.
AB  - Central and peripheral nervous systems may be involved in primary
      hyperparathyroidism (PHP). The efficacy of parathyroidectomy in reversing
      neurological symptoms is still a matter of controversy. We describe the case of a
      71-year-old white male with a 10-year history of PHP who developed progressive
      cognitive dysfunction and severe sensorimotor axonal polyneuropathy. Successful
      parathyroidectomy reversed with a different temporal course both the central and
      peripheral nervous system involvements.

PMID- 10935843
TI  - Dystonia in a patient with deletion of 18p.
AB  - 18p- syndrome from chromosomal deletion of the short arm of chromosome 18 shows a
      wide range of clinical manifestations. Mental retardation is the most frequent
      neurological complication; other neurological deficits are more rarely reported.
      Only one 18p- patient with focal dystonia at the lower limbs has been reported,
      while there have been no reported cases of generalized dystonia. We report a 27
      year-old male with 18p- de novo complete deletion (karyotype 46,XY,18p-) who was
      affected by severe generalized dystonia, hypokinesia, mental retardation and
      dysmorphic features. The 18p- syndrome should be added to the list of genetic
      causes of secondary dystonia. A karyotype analysis should be considered in
      secondary dystonias, particularly when there are associated dysmorphic features
      and mental retardation.

PMID- 10935844
TI  - Type II neurofibromatosis presenting as quadriceps atrophy.
AB  - A young woman aged 26 years presented with atrophy of the left quadriceps
      progressing over one year. Magnetic resonance imaging (MRI) showed a large lesion
      of the lumbar plexus compatible with neurinoma. Cerebral MRI revealed a lesion in
      the right eighth cranial nerve also compatible with neurinoma. On further
      questioning of the patient, it was learned that her mother had undergone surgery
      twice for acoustic neurinoma. Type II neurofibromatosis was diagnosed from the
      basis of clinical picture, neuroimaging findings and family history. This case is
      unusual for the lack of central nervous system (CNS) symptoms. Expansive
      radicular lesions compatible with neurinoma should prompt cerebral MRI. Regular
      examination of family members at risk and early diagnosis can decrease the high
      mortality associated with this condition.

PMID- 10935845
TI  - Conjugal amyotrophic lateral sclerosis: a report on a couple from Sardinia,
      Italy.
AB  - A conjugal case of amyotrophic lateral sclerosis (ALS) observed in Sardinia,
      Italy is reported. This is believed to be the ninth such observation described in
      the literature. The couple had lived together for 38 years in a house adjacent to
      the distillery they owned. No exogenous factors were revealed which could explain
      the genesis of the disease in either patients. Particularly, exposure to alcohol
      does not appear to have been involved in causing ALS. On the basis of statistical
      and epidemiological evaluations, the most likely explanation is that this
      association was purely coincidental.

PMID- 10935846
TI  - Cerebral Whipple's disease: clinical and cerebrospinal fluid findings.
AB  - The case of a patient who had a relapse of cerebral Whipple's disease (WD) one
      year after discontinuation of a two-years' antibiotic treatment is reported.
      Neither the clinical course nor the results of magnetic resonance imaging (MRI)
      and routine examination of the cerebrospinal fluid (CSF) allowed the caring
      physician to predict the relapse. Retrospective analysis of serial specimens of
      CSF showed that slight CSF leucocytosis and intrathecal synthesis of IgA might
      have suggested persistence of infection. The decision to stop antibiotic therapy
      in cerebral WD is difficult, but evaluation of cell counts and of intrathecal
      synthesis of IgA may help in the decision. Some patients may need to take
      treatment indefinitely.

PMID- 10935847
TI  - Bilateral medial frontal infarction in a case of azygous anterior cerebral artery
      stenosis.
AB  - We describe the unusual case of a 63-year-old woman with a history of arterial
      hypertension who presented a sudden weakness of the lower limbs followed by
      mutism, akinesia and dyspraxia. Magnetic resonance images showed a bilateral
      medial frontal infarction. Digital subtraction angiography documented a right
      azygous anterior cerebral artery with severe stenosis in its sub-callosal tract;
      the left anterior cerebral artery showed mild hypoplasia with only sub-frontal
      and fronto-polar branches. No embolic source was documented. Afterwards the
      patient presented a gradual and partial recovery of both motor and cognitive
      functions.

PMID- 10935848
TI  - Headaches in Domestic Medicine by William Buchan.
AB  - In this paper, we consider the chapter on headaches contained in William Buchan's
      Domestic Medicine, a book that enjoyed great success during the second half of
      the eighteenth and the beginning of the nineteenth centuries, and belongs to the
      series of public education treatises that began with the publication of Avis au
      Peuple sur la Sante by Simon Andre Tissot. In line with the ideals of the
      Enlightenment, Buchan's aim was to satisfy the needs of people who had no
      opportunity of consulting a physician by providing them with information about
      the symptoms and treatment of the most common diseases. One of the distinguishing
      characteristics of the book is the space dedicated to preventive medicine. In the
      chapter on headaches, as well as dealing extensively with their etiology,
      pathogenesis, clinical characteristics and treatment within the conceptual
      context of humoral medicine, the author also proposed a number of preventive
      measures that can still be considered fully acceptable today.

PMID- 10935849
TI  - The economic cost of epilepsy: a review.
AB  - Epilepsy is the most prevalent chronic neurologic condition. In developed
      countries, its incidence is 30-50 per 100,000 population per year and the
      prevalence is approximately 5-8 cases per 1,000 population. The rapid growth of
      health care expenditures has led to increased interest in economic evaluation of
      health care programs. We reviewed studies on the costs of epilepsy to assess the
      significance of their quantitative results, through a specific scheme of
      analysis. The main findings of our study are that a general consensus on cost of
      illness evaluation is still remote and many studies lack technical details,
      making difficult any useful comparison of results. New efforts should be realized
      to achieve a major degree of standardization in methodological processes.

PMID- 10935850
TI  - Practice guidelines: a more rational approach to diagnosis and treatment and a
      more effective use of health care resources.
AB  - Practice guidelines are systematically developed statements to assist
      practitioner and patient decisions about appropriate health care for specific
      clinical circumstances. The implementation of practice guidelines is justified by
      factors such as variations in clinical practice, malpractice and its associated
      costs, and the need to contain health care expenditures. In this context,
      practice guidelines promote a more rational approach to clinical decision making
      and better quality of care. Although there are several limitations to the use of
      guidelines in current practice, different organizations (professional societies,
      government agencies, licensing authorities, educational institutions) have a
      potential interest in their development. A working group on the development of
      practice guidelines endorsed by the Italian Society of Neurology has been active
      since 1995. The aims of this group include the development of guidelines to be
      accepted by the medical community and to be placed within the framework of
      initiatives of the Italian Ministry of Health.

PMID- 10935851
TI  - Psychotic disorder after lamotrigine.

PMID- 10935852
TI  - A review of the treatment of primary headaches. Part II: Tension-type headache.
AB  - This paper reviews pharmacological and other approaches currently used to treat
      tension-type headache (TTH), and examines aspects of the classification and
      pathogenesis of this common complaint. Accurate diagnosis is essential before
      treatment is prescribed and should involve complete history taking, thorough
      neurological examination and evaluation of possible associated factors. The most
      frequently used drugs for the acute treatment of TTH are non-steroidal anti
      inflammatory drugs (NSAIDs) of which only some have been shown to be efficacious
      in placebo-controlled trials. Amitriptyline remains the first choice treatment
      for prophylaxis. Other antidepressants, muscle relaxants and benzodiazepines may
      be used, but few have been evaluated adequately in placebo-controlled trials.
      Biofeedback and relaxation training, demonstrated efficacious by controlled
      studies, may be used when the aim is to avoid the side effects of pharmacological
      treatment.

PMID- 10935853
TI  - Central motor conduction after magnetic stimulation in diabetes.
AB  - Central motor conduction times (CMCTs), obtained by means of magnetic stimulation
      of the motor cortex and spinal roots, were studied in 138 patients affected by
      diabetes mellitus but with no signs or symptoms of central nervous system (CNS)
      involvement. CMCTs were significantly increased in diabetic patients (p < 0.001,
      t-test) with respect to normal controls, with values exceeding upper confidence
      limits (mean +/- 2.5 SD of controls) in about 30% of patients. There was no
      correlation between CMCT delay and type of diabetes (insulin-dependent or non
      insulin-dependent), patient age, disease duration, degree of metabolic control
      compensation, presence or absence of retinopathy or nephropathy, and presence or
      absence of peripheral or autonomic neuropathy. CNS involvement in diabetes
      mellitus is discussed. Particular emphasis is given to the sensitivity and
      reliability of CMCTs obtained by means of magnetic stimulation as a tool in the
      early diagnosis of CNS functional alterations in diabetes mellitus.

PMID- 10935854
TI  - Risk of acute cerebrovascular events related to low oestrogen oral contraceptive
      treatment.
AB  - To establish if an association exists between use of oral contraceptives (OC) and
      the occurrence of cerebral arterial thromboembolism, cerebral venous thrombosis
      and retinal vein/artery thrombosis, we identified all women aged 15-44 years
      resident in the province of Parma, Italy, who were hospitalized because of a
      documented cerebral or retinal thromboembolic event during the period 1989-1993.
      The numbers of users and nonusers of OC were estimated from drug sale data and
      demographic statistics for the province. There were 21 cases of cerebral arterial
      thromboembolism during the study period: 10 in OC users and 11 in nonusers, for
      an estimated incidence rate of 1.70 and 0.35 per 10,000 woman-years OC of use and
      nonuse, respectively (RR=4.8, 95% CI = 1.8-9.0). Eight cases of cerebral venous
      thrombosis were observed: 6 in OC users and 2 in nonusers (both in puerperium),
      for an incidence rate of 1.00 and 0.06 per 10,000 woman-years, respectively
      (RR=16.7, 95% CI = 3.3-81.4). Finally, 13 cases of retinal vein/artery thrombosis
      were found: 1 in OC users and 12 in nonusers, for an incidence rate of 0.17 and
      0.37 per 10,000 woman-years, respectively (RR=0.46, 95% CI = 0.06-3.7). In our
      population study the use of low oestrogen OC was associated with an increased
      risk of cerebral venous thrombosis and ischemic stroke, but not of retinal
      vein/artery thrombosis.

PMID- 10935855
TI  - Chronic post-traumatic headache associated with minor cranial trauma: a
      description of cephalalgic patterns.
AB  - We studied a group of 93 patients who had not previously suffered headache and
      who were consecutively admitted to the Emergency Department of the hospitals of
      Novara and Borgomanero, Italy because of a cranial trauma definable as minor
      according to the current International Headache Society (IHS) criteria. Two weeks
      after admission, all patients underwent a semi-structured interview which
      revealed that 24 (25.8%) had headache; 21 of these (22.5% of the original 93
      patients) also had headache when they underwent a second interview eight weeks
      after the traumatic event. These 21 patients were diagnosed as having chronic
      post-traumatic headache associated with minor cranial trauma (5.2.2 of the IHS
      classification), and the prevalent clinical pattern of headache presentation was
      examined with the aim of attributing the fourth IHS classification code number.
      Eighteen of the 21 patients were found to have a tension-type pattern (5.2.2.2),
      and the remaining three had migraine (5.2.2.1); none had cluster headache
      (5.2.2.3). These data demonstrate a large prevalence of tension-type headache in
      patients with class 5.2.2 post-traumatic headache, and confirm the results of
      previously published studies that were not based on the diagnostic criteria of
      the current classification.

PMID- 10935856
TI  - Post-stroke rehabilitation: an economic or medical priority? Current issues and
      prospects in light of new legislative regulations.
AB  - The aim of this study was to evaluate: 1) whether the reduction in duration of in
      patient rehabilitation imposed by the Italian Ministry of Health's circular of
      29/6/95 has been accompanied by a decline in the results achieved; and 2) whether
      the system of basing payments on diagnosis related group (DRG) criteria is
      capable of correctly evaluating differences in post-stroke clinical pictures. The
      study involved 461 of 497 patients consecutively admitted between 1991 and 1996
      for rehabilitation after a first stroke. The average duration of hospitalisation
      for the period 1995-1996 was significantly shorter (p<0.001) than that of the
      previous years; at the same time, there was a significant increase (p<0.05) in
      the number of poor responders in both neurological and functional (mobility)
      terms. Furthermore, the early discharge after 60 days of the 1995-1996 patients
      compromised the stabilisation of recovery and led to a subsequent functional
      decline. It is therefore hoped that the current regulations will be revised and
      that payments based on a functional related group (FRG) criterion will be
      introduced.

PMID- 10935857
TI  - Cyclophosphamide in chronic progressive multiple sclerosis: a comparative study.
AB  - No effective treatment is presently available for progressive multiple sclerosis
      (MS). Cyclophosphamide (CFX), a cytotoxic immunosuppressive drug widely used in
      systemic dysimmune diseases, has been proposed for the treatment of multiple
      sclerosis with different schedules and controversial results. To evaluate the
      safety and clinical efficacy of CFX, we compared three different treatment
      schedules in patients with progressive MS: induction followed by bimonthly
      boosters for one year (17 patients); bimonthly boosters for one year without
      previous induction (15 patients); and monthly boosters for one year (21
      patients). Survival analysis showed that the percentage of stable patients was
      significantly higher in the first and third treatment schedule groups.
      Myelotoxicity occurred in patients treated with induction and boosters (Group A).
      A high incidence of broncopneumonia was observed in patients undergoing the
      second treatment schedule (Group B). No major effects were observed in patients
      treated with monthly boosters (Group C). Response to treatment was limited to
      secondary progressive form. This study suggests that monthly treatment with CFX
      might be safely administered in progressive MS patients; its clinical efficacy
      must be confirmed by an appropriately designed clinical trial.

PMID- 10935858
TI  - Malignant meningeal melanoma.
AB  - We report the case of an isolated pigmented lesion of the cerebellar tentorium
      which was initially interpreted as meningeal melanocytoma. The
      immunohistochemical study required as a result of a subsequent post-surgical
      recurrence prompted us to reconsider the early diagnosis in favour of malignant
      meningeal melanoma. On the basis of data in the literature, the possibility that
      the lesion may have been a dural melanoma is discussed.

PMID- 10935859
TI  - Cerebellar ataxia, hypogonadism and chorioretinopathy: molecular analysis of an
      Italian family.
AB  - This study aimed to determine if cerebellar ataxia, hypogonadism and
      chorioretinopathy (AHCR) is associated with mutations in mitochondrial DNA or in
      genes responsible for spinocerebellar ataxias (SCA1, SCA2, SCA3 and Friedreich's
      ataxia). Two brothers with cerebellar ataxia, hypogonadism and chorioretinopathy
      and their unaffected parents underwent molecular analysis for duplications and
      deletions in mitochondrial DNA (mtDNA), point mutations in the ATP ase 6 gene,
      and expansions of CAG repeats (at 6p22-p23, 12q24.1, 14q32.1) and of GAA repeats
      (at gene X25 on chromosome 9q13). The research was negative for all mutations.
      Our findings confirm that AHCR is a distinct disease within the inherited
      cerebellar ataxias.

PMID- 10935860
TI  - New therapeutic perspectives for demyelinating retrobulbar optic neuritis.
AB  - In patients with demyelinating retrobulbar optic neuritis (RON), a spontaneous or
      corticosteroid-induced improvement is generally observed within the first month,
      but this is clinically insignificant in 5%-7% of patients. We report the case
      histories of four patients who were considered to be "non-responders" to
      corticosteroids because their visus remained unchanged or had improved by only
      1/10 after one month from intravenous corticoid therapy begun 2-7 days after
      disease onset, and who were therefore subsequently administered high intravenous
      doses of immunoglobulin. Three of these patients completely recovered in a period
      of 3-9 months; the fourth showed only a partial improvement, but this was
      consolidated after long-term continuation of the same therapy. These cases
      suggest the possible efficacy of early administration of intravenous
      immunoglobulin in RON patients who fail to respond to cortisone therapy. As
      recently demonstrated in animal models, it can be hypothesised that the result is
      due to immuno-mediated mechanisms of action that reduce autoimmune responses in
      the short- and medium-term, and in the long-term favour remyelination.

PMID- 10935861
TI  - The contribution of Gaetano Perusini to the definition of Alzheimer's disease.
AB  - This paper seeks to examine Perusini's scientific contribution to Alzheimer's
      disease, on the basis of critical reading of the three fundamental papers he
      produced between 1906 and 1911, and published between 1909 and 1911. The
      examination of three publications clearly shows that, after Alzheimer's concise
      clinical report of 3 November 1906, Perusini was responsible for more clearly
      defining its clinical and histopathological characteristics without ever claiming
      be the discoverer of the new disease. The paper also describes Alzheimer's
      express wish to entrust the investigation of the disease to Perusini, and the
      brilliant manner in which this was achieved. The on-going debate on the
      difference between senile and pre-senile dementia, which was originally raised by
      Kraepelin's distinction of the two forms, is also discussed.

PMID- 10935862
TI  - New trends in the management of primary cerebral non-Hodgkin's lymphoma (PCNSL)

PMID- 10935863
TI  - Spectral sharpening with positivity
AB  - Spectral sharpening is a method for developing camera or other optical-device
      sensor functions that are more narrowband than those in hardware, by means of a
      linear transform of sensor functions. The utility of such a transform is that
      many computer vision and color-correction algorithms perform better in a
      sharpened space, and thus such a space can be used as an intermediate
      representation for carrying out calculations. In this paper we consider how one
      may sharpen sensor functions such that the transformed sensors are all positive.
      We show that constrained optimization can be used to produce positive sensors in
      two fundamentally different ways: by constraining the coefficients in the
      transform or by constraining the functions directly. In the former method, we
      prove that convexity can be used to constrain the solution exactly. In a sense,
      we are continuing the work of MacAdam and of Pearson and Yule, who formed
      positive combinations of the color-matching functions. However, the advantage of
      the spectral sharpening approach is that not only can we produce positive curves,
      but the process is "steerable" in that we can produce positive curves with as
      good or better properties for sharpening within a given set of sharpening
      intervals. At base, however, it is positive colors in the transformed space that
      are the prime objective. Therefore we also carry out sharpening of sensor curves
      governed not by positivity of the curves themselves but of colors resulting from
      them. Curves that result have negative lobes but generate positive colors. We
      find that this type of constrained sharpening generates the best results, which
      are almost as good as for unconstrained sharpening but without the penalty of
      negative colors. All methods discussed may be used with any number of sensors.

PMID- 10935864
TI  - Color from shape from color: a simple formalism with known light sources
AB  - Photometric stereo is a well-known technique for recovering surface normals of a
      surface but requires three or more images of a surface taken under illumination
      from different directions. At best, one may dispense with the need for multiple
      images by using colored lights tuned to camera filters. But a less restrictive
      paradigm is available that uses the orientation-from-color approach, wherein
      multiple broadband illuminants impinge on a surface simultaneously. In that
      method, colors for a Lambertian surface lie on an ellipsoid in color space. The
      method has been applied mainly to single-color objects, with ellipsoid quadratic
      form parameters determined from a large number of pixels. However, recently
      Petrov and Antonova [Color Res. Appl. 21, 97 (1996)] developed an entirely local
      approach, useful also for multicolored objects with color uniform in each patch.
      We investigate to what extent a method such as that of Petrov and Antonova can be
      applied in the ostensibly simpler situation in which the complex lighting
      environment is known, i.e., a color photometric stereo situation, with all lights
      in play at once with only a single image to analyze. We find that, assuming a
      simple model of color formation, we are able to recover the object colors along
      with surface normals, using only a single image. Because we immerse the object in
      a known lighting environment, we show that only half of the equations utilized by
      Petrov and Antonova are actually needed, making the method more stable.
      Nevertheless, solutions do not exist at every pixel; instead we may determine a
      best estimate of patch color, using a robust estimator, and then apply that
      estimate throughout a patch. Results are shown to be quite good compared with
      ground truth. The simple color model can often be made to hold more exactly by
      transforming the color space into one corresponding to spectrally sharpened
      sensors, which are a matrix transform away from the actual camera sensors. In our
      study the reliability and accuracy of the normal vector and of the surface color
      recovery algorithm are improved by this straightforward transformation.

PMID- 10935865
TI  - Thresholds for detecting slowly changing Ganzfeld luminances.
AB  - Detection thresholds for luminance increments or decrements are normally related
      to rapid light changes. The goal of this study was to determine detection
      thresholds for slowly changing achromatic Ganzfeld luminances before and after
      adaptation to a constant Ganzfeld illumination, subsequently called Ganzfeld
      adaptation. During Ganzfeld adaptation, perceived brightness decreased slowly and
      leveled off(on average after 5-7 min), despite constant illumination of the
      retina. The state of adaptation was characterized by using magnitude estimation.
      Comparing detection thresholds for changing light intensities before and after
      Ganzfeld adaptation showed that the sensitivity for luminance changes is
      independent of the perceived brightness. A further issue addressed was the time
      dependence of the luminance change. Is there a limit below which a change of
      luminance is no longer perceivable? Even for the slowest gradient tested (0.01
      log/min), subjects were able to detect the change of luminance, although they
      were not able to perceive a continuous brightness change. Similar thresholds (ca.
      0.24 log unit) for shallow and steep luminance gradients suggest an absolute
      luminance detection mechanism. Possible underlying mechanisms and
      neurophysiological substrates are discussed.

PMID- 10935867
TI  - Generalizations of the maximum average correlation height filter
AB  - Recently several approaches have been presented in which the shape of the
      correlation peak is used to distinguish between target and clutter. The well
      known maximum average correlation height (MACH) filter was specifically designed
      to produce similar correlation planes for target variations present in the
      training set. Results are presented of a study of certain generalizations of the
      MACH filter intended to enhance the performance in clutter. It is shown that by
      taking into account the nonoverlapping character of the background noise and
      focusing the MACH correlation plane similarity requirement to the peak
      neighborhood, it is possible to simultaneously achieve a small variation in
      correlation peak shape and high peak-to-sidelobe ratios for cluttered images.

PMID- 10935866
TI  - Analysis of the performance of the Hartmann-Shack sensor in the human eye.
AB  - A description of a Hartmann-Shack sensor to measure the aberrations of the human
      eye is presented. We performed an analysis of the accuracy and limitations of the
      sensor using experimental results and computer simulations. We compared the
      ocular modulation transfer function obtained from simultaneously recorded double
      pass and Hartmann-Shack images. The following factors affecting the sensor
      performance were evaluated: the statistical accuracy, the number of modes used to
      reconstruct the wave front, the size of the microlenses, and the exposure time.

PMID- 10935868
TI  - Effect of compensation for spherical aberration on the transverse displacement of
      laser speckle patterns
AB  - When a rough surface illuminated by coherent light is displaced perpendicularly
      to the optical axis of an imaging optical system the speckle pattern in the
      conjugate plane is transversally displaced too. This displacement has two
      components. The first one is proportional to the object displacement, and the
      second one depends on wave-front aberrations and, consequently, is strongly
      related to the optical system that is used. Usually, well-corrected photographic
      objectives are used for the measurement of transverse displacements by double
      exposure laser speckle photography. Since in well-corrected objectives
      aberrations tend to compensate one another, it seems that the complementary
      displacement of the speckle pattern, caused by aberrations, is near zero and does
      not affect the accuracy of the measurement. Here it is analytically shown that
      the compensation of spherical aberrations does not guarantee a negligible
      complementary displacement. From the results obtained it follows that well
      corrected objectives for laser speckle photography can be regarded as a
      particular class of photographic objectives, since they not only yield high
      quality images but also minimize complementary displacement.

PMID- 10935869
TI  - Radiometric theory of spatial coherence in free-space propagation
AB  - The radiometric theory of spatial coherence is presented with special attention
      to the validity of the approximations on which it is based. A new definition of
      the transverse coherence area is introduced and shown to be in general agreement
      with earlier definitions. In free-space propagation the product of the transverse
      coherence area and the intensity is shown to be constant along rectilinear rays,
      and, for radiation from uniform Lambert sources, a well-known paraxial formula
      for the transverse coherence area is extended to the extraparaxial domain. A
      decrease of the spatial coherence in free-space propagation takes place in
      regions with an increase of the intensity. For imaging systems this occurs in a
      finite part of image space whenever a real image of a diffusely radiating,
      extended object is formed at a finite distance.

PMID- 10935870
TI  - Acousto-optic superlattice modulation in fiber Bragg gratings
AB  - The superposition of a long-period grating and a fiber Bragg grating, which we
      call an optical superlattice, causes high-efficiency narrow-band reflections to
      be induced on either side of the Bragg wavelength. This effect was recently
      observed experimentally in a fiber-based acousto-optic superlattice modulator. We
      develop in detail the theory of optical superlattices in fiber Bragg gratings,
      treating both the acousto-optic and the fixed-grating cases. Applications include
      reconfigurable wavelength division multiplexers, fiber lasers and sensors,
      tunable filters, modulators, and frequency shifters.

PMID- 10935871
TI  - Centroid gain compensation in Shack-Hartmann adaptive optics systems with natural
      or laser guide star
AB  - In an adaptive optics system with an undersampled Shack-Hartmann wave-front
      sensor (WFS), variations in seeing, laser guide star quality, and sodium layer
      thickness and range distance all combine to vary WFS centroid gain across the
      pupil during an exposure. While using the minimum of 4 pixels per WFS subaperture
      improves frame rate and read noise, the WFS centroid gain uncertainty may
      introduce static aberrations and degrade servo loop phase margin. We present a
      novel method to estimate and compensate WFS gains of each subaperture
      individually in real time for both natural and laser guide stars.

PMID- 10935872
TI  - Adaptive optics based on analog parallel stochastic optimization: analysis and
      experimental demonstration
AB  - Wave-front distortion compensation using direct system performance metric
      optimization is studied both theoretically and experimentally. It is shown how
      different requirements for wave-front control can be incorporated, and how
      information from different wave-front sensor types can be fused, within a
      generalized gradient descent optimization paradigm. In our experiments a very
      large-scale integration (VLSI) system implementing a simultaneous perturbation
      stochastic approximation optimization algorithm was applied for real-time
      adaptive control of multielement wave-front correctors. The custom-chip
      controller is used in two adaptive laser beam focusing systems, one with a 127
      element liquid-crystal phase modulator and the other with beam steering and 37
      control channel micromachined deformable mirrors. The submillisecond response
      time of the micromachined deformable mirror and the parallel nature of the analog
      VLSI control architecture provide for high-speed adaptive compensation of
      dynamical phase aberrations of a laser beam under conditions of strong intensity
      scintillations. Experimental results demonstrate improvement of laser beam
      quality at the receiver plane in the spectral band up to 60 Hz.

PMID- 10935873
TI  - Optical properties of a thin-film stack illuminated by a focused field
AB  - Reflectance (R), transmittance (T), and absorptance (A) are calculated for a thin
      film stack illuminated by a focused field. Based on Debye's integral
      representation, the electric and magnetic fields near focus are obtained, and the
      formulas for R, T, and A are represented as integrals of Poynting vectors. This
      formulation is applied to the case of a numerical aperture (N.A.) greater than
      1.0 as well as to the case of a N.A. less than 1.0, and the corresponding
      numerical results are presented. They reveal that R, T, and A vary with N.A. and
      that the amount of variation increases with layer thickness.

PMID- 10935874
TI  - Optical filters consisting of metallic waveguide arrays
AB  - We demonstrate high-pass optical filters with cutoffs in the 0.3-10-micron
      spectral region. These filters consist of uniform arrays of hollow metallic
      waveguides, obtained by coating wafers of the previously developed channel-glass
      (CG) materials with a thin metal film. In these filters the channel diameter
      controls the cutoff frequency, the channel length controls the sharpness of the
      cutoff, and the channel density determines the transmission efficiency at cutoff.
      All of these parameters can be controlled in the CG starting material. The
      properties of the metal coatings that influence the filter properties are also
      discussed. Cutoff wavelengths near 300 nm have been achieved to date by using CG
      materials with submicrometer channel diameters. At all channel diameters, the
      transmission spectra include a peak just above the cutoff wavelength, where the
      transmission value can exceed that expected on the basis of the geometrical open
      area of the CG structure.

PMID- 10935875
TI  - Maxwell equations and the k function
AB  - We use a general solution to the eikonal equation to define generalized
      coordinates in terms of which the Maxwell equations are then cast. These
      coordinates are then used to obtain expressions for the electric and magnetic
      field vectors and the Poynting vector. An arbitrary vector function V is
      introduced that is subject to certain side conditions derived in this process.
      The k function, the arbitrary function that arises in the solution of the eikonal
      equation, contains only information descriptive of the geometry of a wave-front
      train. The vector function V contains information pertaining to the physics of
      the propagating energy that is distinct from the geometry of the wave-front
      train.

PMID- 10935876
TI  - Fresnel formulas as Lorentz transformations
AB  - From a matrix formulation of the boundary conditions we obtain the fundamental
      invariant for an interface and a remarkably simple factorization of the interface
      matrix, which enables us to express the Fresnel coefficients in a new and compact
      form. This factorization allows us to recast the action of an interface between
      transparent media as a hyperbolic rotation. By exploiting the local isomorphism
      between SL(2, C) and the (3 + 1)-dimensional restricted Lorentz group SO(3, 1),
      we construct the equivalent Lorentz transformation that describes any interface.

PMID- 10935877
TI  - Finite mode analysis through harmonic waveguides
AB  - The mode analysis of signals in a multimodal shallow harmonic waveguide whose
      eigenfrequencies are equally spaced and finite can be performed by an
      optoelectronic device, of which the optical part uses the guide to sample the
      wave field at a number of sensors along its axis and the electronic part computes
      their fast Fourier transform. We illustrate this process with the Kravchuk
      transform.

PMID- 10935878
TI  - Stochastic independence of color-vision mechanisms confirmed by a subthreshold
      summation paradigm.
AB  - We have used a subthreshold summation protocol to analyze spatial color-color
      interaction. By means of a CRT color monitor, we measured the threshold contours
      for a spatial frequency of 0.5 cycles/degree. Heterochromatic flicker photometry
      was used to obtain isoluminance. The results suggest that the blue-yellow (b-y)
      and red-green (r-g) contrast thresholds remained unchanged by the addition of
      fixed r-g and b-y subthreshold pedestals. Our subthreshold summation data then
      support the stochastic independence of colorvision mechanisms derived from Mullen
      and Sankeralli's work [Vision Res. 39, 733 (1999)] despite the differences that
      exist between the two experimental methods.

PMID- 10935879
TI  - Urease activity may contribute to the ability of Actinobacillus pleuropneumoniae
      to establish infection.
AB  - The contribution of urease activity to the pathogenesis of Actinobacillus
      pleuropneumoniae was investigated using 2 different urease-negative transposon
      mutants of the virulent serotype 1 strain, CM5 Nalr. One mutant, cbiK::Tn10, is
      deficient in the uptake of nickel, a cofactor required for urease activity. The
      other mutant, ureG::Tn10, is unable to produce active urease due to mutation of
      the urease accessory gene, ureG. In aerosol challenge experiments, pigs developed
      acute pleuropneumonia following exposure to high doses (10(6) cfu/mL) of the
      parental strain, CM5 Nalr, and to the cbiK::Tn10 mutant. When low dose (10(3)
      cfu/mL) challenges were used, neither urease-negative mutant was able to
      establish infection, whereas the parental strain was able to colonize and cause
      lesions consistent with acute pleuropneumonia in 8 of the 20 pigs challenged.
      These findings suggest that urease activity may be needed for A. pleuropneumoniae
      to establish infection in the respiratory tract of pigs.

PMID- 10935880
TI  - Bovine viral diarrhea viral infections in feeder calves with respiratory disease:
      interactions with Pasteurella spp., parainfluenza-3 virus, and bovine respiratory
      syncytial virus.
AB  - The prevalence of bovine viral diarrhea virus (BVDV) infections was determined in
      a group of stocker calves suffering from acute respiratory disease. The calves
      were assembled after purchase from Tennessee auctions and transported to western
      Texas. Of the 120 calves, 105 (87.5%) were treated for respiratory disease.
      Sixteen calves died during the study (13.3%). The calves received a modified live
      virus BHV-1 vaccine on day 0 of the study. During the study, approximately 5 wk
      in duration, sera from the cattle, collected at weekly intervals, were tested for
      BVDV by cell culture. Sera were also tested for neutralizing antibodies to BVDV
      types 1 and 2, bovine herpesvirus-1 (BHV-1), parainfluenza-3 virus (PI-3V), and
      bovine respiratory syncytial virus (BRSV). The lungs from the 16 calves that died
      during the study were collected and examined by histopathology, and lung
      homogenates were inoculated onto cell cultures for virus isolation. There were no
      calves persistently infected with BVDV detected in the study, as no animals were
      viremic on day 0, nor were any animals viremic at the 2 subsequent serum
      collections. There were, however, 4 animals with BVDV type 1 noncytopathic (NCP)
      strains in the sera from subsequent collections. Viruses were isolated from 9
      lungs: 7 with PI-3V, 1 with NCP BVDV type 1, and 1 with both BVHV-1 and BVDV. The
      predominant bacterial species isolated from these lungs was Pasteurella
      haemolytica serotype 1. There was serologic evidence of infection with BVDV types
      1 and 2, PI-3V, and BRSV, as noted by seroconversion (> or = 4-fold rise in
      antibody titer) in day 0 to day 34 samples collected from the 104 survivors:
      40/104 (38.5%) to BVDV type 1; 29/104 (27.9%) to BVDV type 2; 71/104 (68.3%) to
      PI-3V; and 81/104 (77.9%) to BRSV. In several cases, the BVDV type 2 antibody
      titers may have been due to crossreacting BVDV type 1 antibodies; however, in 7
      calves the BVDV type 2 antibodies were higher, indicating BVDV type 2 infection.
      At the outset of the study, the 120 calves were at risk (susceptible to viral
      infections) on day 0 because they were seronegative to the viruses: 98/120
      (81.7%), < 1:4 to BVDV type 1; 104/120 (86.7%) < 1:4 to BVDV type 2; 86/120
      (71.7%) < 1:4 to PI-3V; 87/120 (72.5%) < 1:4 to BRSV; and 111/120 (92.5%) < 1:10
      to BHV-1. The results of this study indicate that BVDV types 1 and 2 are involved
      in acute respiratory disease of calves with pneumonic pasteurellosis. The BVDV
      may be detected by virus isolation from sera and/or lung tissues and by serology.
      The BVDV infections occurred in conjunction with infections by other viruses
      associated with respiratory disease, namely, PI-3V and BRSV. These other viruses
      may occur singly or in combination with each other. Also, the study indicates
      that purchased calves may be highly susceptible, after weaning, to infections by
      BHV-1, BVDV types 1 and 2, PI-3V, and BRSV early in the marketing channel.

PMID- 10935881
TI  - Use of L4 larvae of Nippostrongylus brasiliensis for the in vivo screening of
      anthelmintic drugs.
AB  - Five groups of Wistar rats were subcutaneously infected with 5,000 L3 stage
      larvae of Nippostrongylus brasiliensis. Four groups were dosed orally with 5, 10,
      15, and 20 mg/kg body weight of albendazole at 5 h postinfection, and one group
      served as an untreated control. The animals were euthanized and the intestines
      were dissected out 72 h postinfection and were incubated on a Baermann's
      apparatus to recover L4 stage larvae. No larvae were recovered from the 20 mg/kg
      albendazole-treated group, and means of 15, 33, and 175 L4 larvae were recovered
      from the 15, 10, and 5 mg/kg albendazole-treated groups, respectively. Levamisole
      and fenbendazole were also tested using the same procedure. Means of 100 and
      1,887 L4 larvae were obtained from the 50 and 10 mg/kg of levamisole-treated
      groups respectively; while, 191 and 583 L4 larvae were recovered from rats
      treated with 50 and 10 mg/kg of fenbendazole, respectively. These results
      indicate that the L4 stage of N. brasiliensis could be useful for in vivo
      screening of new nematocide drugs.

PMID- 10935882
TI  - Development and validation of a method for simultaneous separation and
      quantification of 5 different sugars in canine urine.
AB  - The objective of this project was to develop and validate a method for concurrent
      separation and quantification of methylglucose, rhamnose, xylose, sucrose, and
      lactulose in canine urine by using high pressure anion exchange liquid
      chromatography and pulsed amperometric detection. The method was validated by
      evaluating dilutional parallelism, spiking recovery, intra-assay variability, and
      inter-assay variability. Observed to expected ratios for 3 urine samples, and all
      sugars, ranged from 77.6% to 106.9% for a 1:2 dilution, 85.2% to 121.4% for a 1:4
      dilution, and 91.6% to 163.7% for a 1:8 dilution. Observed to expected ratios for
      spiking recovery of 3 urine samples, all sugars, and 5 different spiking
      solutions, ranged from 85.5% to 116.7 % (mean +/- SD, 100.5 +/- 6.0%). The intra
      assay coefficients of variation were 1.6%, 3.4%, and 4.7% for methylglucose;
      1.6%, 2.0%, and 3.6% for rhamnose; 2.7%, 1.4%, and 1.1% for xylose; 9.8%, 3.4%,
      and 4.0% for sucrose; and 3.2%, 3.3%, and 3.3% for lactulose. Inter-assay
      coefficients of variation were 3.2%, 5.7%, and 4.2% for methylglucose; 4.3%,
      5.4%, and 6.4% for rhamnose; 3.3%, 5.0%, and 4.2% for xylose; 9.4%, 9.9%, and
      9.4% for sucrose; and 6.1%, 4.9%, and 2.7% for lactulose. In conclusion, a method
      for simultaneous separation and quantification of 5 sugars in canine urine was
      established and found to be linear, accurate, precise, and reproducible. This
      method may prove useful in the simultaneous evaluation of gastric permeability,
      small intestinal permeability, and small intestinal mucosal function in dogs with
      gastrointestinal disorders.

PMID- 10935883
TI  - Serum concentrations and pharmacokinetics of enrofloxacin after intravenous and
      intragastric administration to mares.
AB  - Serum concentrations and pharmacokinetics of enrofloxacin were studied in 6 mares
      after intravenous (IV) and intragastric (IG) administration at a single dose rate
      of 7.5 mg/kg body weight. In experiment 1, an injectable formulation of
      enrofloxacin (100 mg/mL) was given IV. At 5 min after injection, mean serum
      concentration was 9.04 microg/mL and decreased to 0.09 microg/mL by 24 h.
      Elimination half-life was 5.33 +/- 1.05 h and the area under the serum
      concentration vs time curve (AUC) was 21.03 +/- 5.19 mg x h/L. In experiment 2,
      the same injectable formulation was given IG. The mean peak serum concentration
      was 0.94 +/- 0.97 microg/mL at 4 h after administration and declined to 0.29 +/-
      0.12 microg/mL by 24 h. Absorption of this enrofloxacin preparation after IG
      administration was highly variable, and for this reason, pharmacokinetic values
      for each mare could not be determined. In experiment 3, a poultry formulation
      (32.3 mg/mL) was given IG. The mean peak serum concentration was 1.85 +/- 1.47
      microg/mL at 45 min after administration and declined to 0.19 +/- 0.06 microg/mL
      by 24 h. Elimination half-life was 10.62 +/- 5.33 h and AUC was 16.30 +/- 4.69 mg
      x h/L. Bioavailability was calculated at 78.29 +/- 16.55%. Minimum inhibitory
      concentrations of enrofloxacin were determined for equine bacterial culture
      specimens submitted to the microbiology laboratory over an 11-month period. The
      minimum inhibitory concentration of enrofloxacin required to inhibit 90% of
      isolates (MIC90) was 0.25 microg/mL for Staphylococcus aureus, Escherichia coli,
      Salmonella spp., Klebsiella spp., and Pasteurella spp. The poultry formulation
      was well tolerated and could be potentially useful in the treatment of
      susceptible bacterial infections in adult horses. The injectable enrofloxacin
      solution should not be used orally.

PMID- 10935884
TI  - Identification of hydroxyropivacaine glucuronide in equine urine by ESI+/MS/MS.
AB  - Ropivacaine is a local anesthetic that has a high potential for abuse in racing
      horses. It can be recovered from urine collected after administration as a
      hydroxylated metabolite following beta-glucuronidase treatment of the urine.
      Based on these findings, it has been inferred that ropivacaine is present in
      equine urine as a glucuronide metabolite; however, these metabolites have never
      been directly identified. Using ESI+/MS/MS, the presence of a [M+H]+ molecular
      ion of m/z 467 was demonstrated in urine corresponding to the calculated mass of
      a hydroxyropivacaine glucuronide +1. The abundance of this ion diminished after
      glucuronidase treatment with concomitant appearance of a m/z 291 peak, which is
      consistent with its hydrolysis to hydroxyropivacaine. In further work, the m/z
      467 material was fragmented in the MS/MS system, yielding fragments interpretable
      as hydroxyropivacaine glucuronide. These data are consistent with the presence of
      a hydroxyropivacaine glucuronide in equine urine and constitute the first direct
      demonstration of a specific glucuronide metabolite in equine urine.

PMID- 10935885
TI  - Retrospective serological survey of antibodies to porcine circovirus type 1 and
      type 2.
AB  - A retrospective serological survey was performed to determine the presence of
      antibodies to porcine circovirus type 1 (PCV1) and porcine circovirus type 2
      (PCV2) in serum samples collected from sows at slaughterhouses in Canada in 1985,
      1989, and 1997. Each serum sample was tested by indirect immunofluorescence on
      PCV-free PK15 cells, on PCV1-infected PK15 cells and on PCV2-infected PK15 cells.
      For the 3 years studied, sera positive to PCV1 and PCV2 were identified and the
      number of sera positive for PCV2 was greater than the number of sera positive for
      PCV1. The results indicated 1) that PCV2 appears to be the main PCV type
      circulating in the Canadian pig population, 2) that PCV2 had been circulating in
      the Canadian pig population at least 10 years before the postweaning
      multisystemic wasting syndrome (PMWS) was reported, and 3) that serological
      evaluation using PCV1 underestimates the seroprevalence of PCV2.

PMID- 10935887
TI  - Minimally invasive approach to canine pericardiectomy.

PMID- 10935886
TI  - Interleukin-2 and concanavalin A upregulate a cat2 isoform encoding a high
      affinity L-arginine transporter in feline lymphocytes.
AB  - The immunological responses of activated lymphocytes are associated with
      increased nitric oxide (NO) biosynthesis. Studies in the literature have
      primarily approached control of NO by focusing on the regulation of the nitric
      oxide synthase (NOS) isoforms. However, the present study approaches the control
      of NO synthesis by addressing the regulation of L-arginine availability to
      lymphocytes via regulation of membrane transport. The guanidino nitrogen of L
      arginine is the sole biosynthetic precursor of NO. We investigated cytokine and
      mitogen regulation of membrane L-arginine transporters for the first time in
      feline cells. Feline peripheral blood mononuclear cells were treated with
      interleukin-2 and concanavalin A, then alternatively spliced isoforms of L
      arginine transporters known in other species were probed by RT-PCR, using various
      oligonucleotide primers that hybridized to several regions in common with the
      isoforms. Both high affinity and low affinity isoforms are encoded by mRNAs
      arising from mutually exclusive alternative splicing of the primary transcript. A
      region of 123 bp was obtained that encoded an extracellular polypeptide loop of
      41 amino acids. The sequence of this region represented the high affinity L
      arginine substrate binding site of a CAT2 transporter polypeptide isoform, but
      not the CAT2a isoform low affinity binding site. Neither of the inducible
      isoforms were constitutively expressed in unstimulated feline cells. This is the
      first report demonstrating that domestic cats possess the cat2 gene encoding an
      inducible L-arginine transporter, and, furthermore, that the high affinity
      isoform transcript is activated by interleukin-2 and concanavalin A in feline
      lymphocytes.

PMID- 10935888
TI  - Perils and pitfalls of clinical trials--experience from human oncology.

PMID- 10935889
TI  - Canine hemangiosarcoma treated with standard chemotherapy and minocycline.
AB  - Standard treatments for canine hemangiosarcoma include surgery and chemotherapy
      with doxorubicin, but in spite of treatment most dogs with this disease die
      within 6 months of diagnosis. Tumor growth and metastasis are angiogenesis
      dependent. Antiangiogenic drugs such as minocycline may provide therapeutic
      benefits in cancer patients. The purpose of this prospective study was to
      evaluate the efficacy of chemotherapy with doxorubicin and minocycline, an
      antiangiogenic agent, in dogs with hemangiosarcoma. Eighteen dogs with
      histologically confirmed hemangiosarcoma of any stage were treated with
      doxorubicin, cyclophosphamide, and minocycline. Complete staging was performed
      before and during the treatment period to assess remission status and response to
      therapy. No statistically significant difference was found in survival between
      the dogs treated with chemotherapy and minocycline, and historical controls
      consisting of dogs that received chemotherapy alone. Postmortem examination
      revealed widespread metastasis, suggesting that minocycline is ineffective as a
      single antiangiogenic agent in canine hemangiosarcoma.

PMID- 10935890
TI  - The blood-brain barrier and its role in inflammation.
AB  - The unique microenvironment within the central nervous system (CNS) relies upon
      the integrity of the blood-brain barrier (BBB). This selectively permeable
      barrier comprises interendothelial tight junctions located at the capillaries and
      postcapillary venules. Cells and structures in the local environment are required
      to maintain normal BBB function. When inflammation is present, the BBB itself
      plays an integral role in the inflammatory response by either producing or
      expressing a variety of cytokines, adhesion molecules, metalloproteinases, serine
      proteases, products of arachidonic acid metabolism, and nitric oxide.
      Understanding the role of the BBB during inflammation is essential when creating
      and employing a therapeutic regime for animals with CNS disease. This review
      focusses on recent discoveries about the BBB and its role in inflammation, and
      applies this knowledge to our current understanding of inflammatory CNS disease
      in dogs and cats.

PMID- 10935891
TI  - Use of a prestorage leukoreduction filter effectively removes leukocytes from
      canine whole blood while preserving red blood cell viability.
AB  - Leukoreduction of blood products is a technique used to prevent leukocyte-induced
      transfusion reactions. Filters currently used for human blood products achieve at
      least a 99.9% reduction in leukocyte numbers per unit (450 mL) of blood. Goals of
      this study were to determine if a prestorage leukoreduction filter could
      effectively achieve leukoreduction of canine blood and to determine if viability
      of the leukoreduced red blood cell (RBC) product could be maintained after 35
      days of storage. Blood collected from each dog was filtered through a
      leukoreduction filter at either room temperature or after cooling (4 degrees C)
      for 4 hours. Filtration efficacy was determined by measurement of pre- and
      postfiltration leukocyte counts. In vitro viability of RBCs was determined by
      comparing RBC adenosine triphosphate concentration and percent hemolysis before
      and after the storage period. In vivo viability of stored cells was determined
      using a biotin-streptavidin-phycoerythrin labeling technique and flow cytometry.
      Blood filtered within 30 minutes of collection versus blood filtered after
      cooling had mean reductions in leukocyte numbers of 88.90 and 99.99%,
      respectively. The mean ATP and hemoglobin concentrations from the in vitro
      analysis were comparable to those obtained in previously for canine RBC
      adequately stored for 35 days. The mean in vivo 24-hour survival of the stored
      RBC was 84.7%. The leukoreduction filter used did not adversely affect in vitro
      or in vivo viability of canine RBCs. The filter effectively removed leukocytes
      from blood, with maximal efficiency of filtration achieved with use of cooled
      blood.

PMID- 10935892
TI  - Electrically induced blink reflex and facial motor nerve stimulation in beagles.
AB  - Electrophysiologic assessment of the blink reflex test and the muscle-evoked
      potentials evoked by stimulation of the facial nerve were performed in 15 healthy
      adult Beagles before and after supraorbital (trigeminal) and facial anesthetic
      nerve blocks performed by lidocaine injections. Unilateral electrical stimulation
      of the supraorbital nerve elicited 2 ipsilateral (R1 and R2) and a contralateral
      (Rc) reflex muscle potential in orbicularis oculi muscles. Electrical stimulation
      of the facial nerve elicited 2 muscle potentials (a direct response [D] and a
      reflex faciofacial response [RF]) in the ipsilateral orbicularis oculi muscle.
      Anesthetic block of the left supraorbital nerve resulted in bilateral lack of
      responses upon left supraorbital nerve stimulation, but normal responses in right
      and left orbicularis oculi muscles upon right supraorbital stimulation. Right
      facial anesthetic block produced lack of responses in the right orbicularis oculi
      muscle regardless the side of supraorbital nerve stimulation. Results of this
      study demonstrate that the blink reflex can be electrically elicited and assessed
      in dogs. Reference values for the blink reflex responses and for the muscle
      potentials evoked by direct facial nerve stimulation in dogs are provided. The
      potential usefulness of the electrically elicited blink reflex test in the
      diagnosis of peripheral facial and trigeminal dysfunction in dogs was
      demonstrated.

PMID- 10935893
TI  - Brainstem auditory evoked potential wave V latency-intensity function in normal
      Dalmatian and Beagle puppies.
AB  - This study investigated whether Dalmatian puppies with normal hearing bilaterally
      had the same click-evoked brainstem auditory potential characteristics as age
      matched dogs of another breed. Short-latency brainstem auditory potentials evoked
      by condensation and rarefaction clicks were recorded in 23 1.5- to 2-month-old
      Dalmatian puppies with normal hearing bilaterally by a qualitative brainstem
      auditory evoked potential test and in 16 Beagle dogs of the same age. For each
      stimulus intensity, from 90 dB normal hearing level down to the wave V threshold,
      the sum of the potentials evoked by the 2 kinds of stimuli were added, giving an
      equivalent to the alternate click polarity stimulation. The slope of the L
      segment of the wave V latency-intensity curve was steeper in Dalmatian (-40 +/-
      10 micros/dB) than in Beagles (-28 +/- 5 micros/dB, P < .001) puppies. The
      hearing threshold was lower in the Beagle puppies (P < .05). These results
      suggest that interbreed differences may exist at the level of cochlear function
      in this age class. The wave V latency and wave V-wave I latencies differences at
      high stimulus intensity were different between the groups of puppies (4.3 +/- 0.2
      and 2.5 +/- 0.2 milliseconds, respectively, for Beagles; and 4.1 +/- 0.2 and 2.3
      +/- 0.2 milliseconds for Dalmatians, P < .05). A different maturation speed of
      the neural pathways is one possible explanation of this observation.

PMID- 10935894
TI  - Evaluation of four 2-dimensional echocardiographic methods of assessing left
      atrial size in dogs.
AB  - Two-dimensional (2D) echocardiography is the cornerstone of noninvasive
      evaluation of the cardiac patient, and often involves estimating left atrial (LA)
      size. However, 2D echocardiographic methods of estimating LA size have been
      inadequately described, and most reference intervals are based on M-mode
      echocardiographic measurements. We determined reference intervals for 4 different
      2D echocardiographic methods of estimating LA size in adult (> or =9-month-old)
      dogs without cardiovascular disease. Thirty-six dogs, placed in right lateral
      recumbency, were examined by 2D echocardiography. The left atrium was measured at
      specific time points in the cardiac cycle. Measurement methods were LA diameter
      in short axis, LA diameter in long axis, LA circumference in short axis, and LA
      cross-sectional area in short axis. Comparisons of these LA dimensions to
      appropriate aortic dimensions provided body weight-independent estimates of LA
      size. We found strong associations of LA dimensions with body weight (r2 = .76
      .88). Comparable body weight-independent 2D echocardiographic estimates of LA
      size in short axis exceeded historical M-mode reference intervals. These data
      provide echocardiographers with reference intervals for 2D echocardiographic
      estimates of LA size in adult dogs.

PMID- 10935895
TI  - Effects of acute gastric distention and recovery on tendency for ventricular
      arrhythmia in dogs.
AB  - The gastric distention-volvulus (GDV) syndrome occurs commonly in large-breed
      dogs and may prove fatal in 15-68% of cases. Approximately 43% of cases with
      gastric distention (GD) or volvulus develop cardiac arrhythmias that can
      contribute to mortality. Most of these arrhythmias are ventricular in origin and
      ventricular fibrillation (VF) may be the cause of death. This study used an
      iatrogenic model of acute GD to investigate the prevalence of ventricular
      arrhythmias during acute GD and its recovery, if programmed electrical
      stimulation (PES) may uncover tendency to VF, if the Q-T interval corrected for
      heart rate (Q-Tc) of the electrocardiogram (ECG) predicts tendency to VF, and if
      hemodynamic changes predate VF. Eleven beagles, anesthetized with morphine and
      alpha-chloralose, and instrumented so that vascular pressures, cardiac output,
      and PES could be recorded, were used. Five were unperturbed, whereas acute GD to
      a pressure of 30 mm Hg for 1.5 hours was produced in 6 others. The results were
      as follows. No dogs with GD developed spontaneously occurring arrhythmias. VF was
      produced in no dogs by conventional PES, but occurred in all dogs (P < .05) with
      GD and none of the controls, using accelerated ventricular pacing. The Q-Tc
      interval of the ECG prolonged minimally in dogs with GD, and shortened (P < .05)
      in controls. Some hemodynamic changes did predate VF. In conclusion, dogs with
      acute GD have a tendency for VF, which may be uncovered by accelerated PES. The
      mechanism for the vulnerability to arrhythmia with GD is unknown.

PMID- 10935897
TI  - Transcatheter closure of patent ductus arteriosus using occluding spring coils.
AB  - The purpose of this study is to report our initial experience with the use of
      spring coils to close the patent ductus arteriosus in the dog. There are few
      large-patient series reported in the veterinary literature. Coil closure was
      attempted in 15 dogs (median weight, 6.5 kg; range, 1.2 to 38.7 kg) presenting
      with a patent ductus arteriosus between May 1997 and May 1999. Arterial
      catheterization followed by angiography was used to decide if coil placement was
      adequate. A 5- or 8-mm embolization coil, depending on the angiographic diameter
      of the ductus, was delivered, with 1 loop in the pulmonary arterial side and the
      remainder of the coil in the aortic side of the duct. Additional coils were used
      if a residual shunt was present, and closure was confirmed by aortography.
      Patients were discharged the day after the procedure. Successful coil closure,
      without residual shunt on angiography, was achieved in 11 of 13 dogs in which
      coils were released. In 6 dogs, a coil embolized to the pulmonary artery. Four of
      these dogs had successful closure with multiple coils, and 2 others had surgery.
      None of these dogs experienced adverse effects. In 2 dogs with conical patent
      ductus arteriosus >5 mm in minimal diameter, coil closure was not done. We
      conclude that the patent ductus arteriosus size and anatomical shape are crucial
      in deciding whether coil closure is the method of choice. In selected cases, coil
      closure represents an elegant alternative to surgical ligation. Although
      pulmonary embolism occurred commonly, it did not cause any obvious clinical
      problem.

PMID- 10935896
TI  - Cardiovascular effects of intravenous diltiazem in dogs with iatrogenic atrial
      fibrillation.
AB  - Atrial fibrillation (AF) was induced in anesthetized Beagle hounds to determine
      the dose of diltiazem (D) that resulted in hemodynamic function similar to that
      observed during sinus rhythm (SR). Dogs were instrumented to record hemodynamic
      and electrophysiological parameters. Six dogs were given D, IV at cumulative
      doses of 0.063, 0.188, 0.438, 0.938, and 1.938 mg/kg, whereas 6 other dogs
      received vehicle in equivalent volumes. Plasma concentrations (PC) of D were
      measured. A cumulative dose of D between 0.438 and 0.938 mg/kg produced PC of
      67.8 to 117.4 ng/mL and resulted in a heart rate (HR) closest to that observed
      during SR. At doses up to 0.938 mg/kg, no parameter of systolic function fell
      below that obtained during SR. At a dose of 0.938 mg/kg, the left ventricular end
      diastolic and right atrial pressures exceeded those during SR. The rate-pressure
      product did not differ from that during SR at a dose of 0.938 mg/kg and fell
      below that during SR at the dose of 1.938 mg/kg. Left ventricular efficiency
      decreased from SR to AF, returned to values not different from those during SR at
      a dose of 0.938 mg/kg, and increased to values above those observed during SR at
      a dose of 1.938 mg/kg. In AF, slowing the HR with 0.438-0.938 mg/kg of D with
      resultant PC of 67.8-117.4 ng/mL results in cardiovascular function not different
      from that observed during SR.

PMID- 10935898
TI  - Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.
AB  - A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was
      performed in order to characterize the disease and to identify potential
      prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of
      6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador
      Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive
      and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested
      positive for the presence of immunoglobulin on the red blood cell surface (Coombs
      assay). The most common clinical signs at presentation were lethargy, weakness,
      pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25%
      was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a
      nonregenerative anemia, whereas 25 patients (42%) had a regenerative response.
      Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged
      prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin
      clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All
      dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single
      or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty
      one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9
      dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a
      lower dose (50 mg/m2 q24h). No statistical difference in survival times was found
      for either protocol. Thirteen dogs were treated with azathioprine in addition to
      cyclophosphamide and prednisone. The median survival time of dogs that received
      all 3 drugs was 370 days as compared to 9 days for those dogs that were treated
      with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the
      disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The
      median length of survival for all dogs was 21 days. Eight dogs that were
      discharged from the hospital suffered a relapse (PCV < 25%).

PMID- 10935899
TI  - Tolerance of a rice-based oral rehydration solution given to normal calves.
AB  - The objective of the study was to test the tolerance of a rice-based oral
      rehydration formula when fed to calves. Six healthy Holstein calves, 1 week of
      age, were fed the formula instead of milk replacer for 3 days. Pre- and
      posttreatment results of clinical examination and laboratory parameters were
      compared. Vital signs, attitude, appetite, clinical hydration status, urine
      specific gravity, and most routine serum biochemistry test results did not vary
      and remained within the normal range. Five of the 6 calves developed diarrhea
      when fed the rice-based formula, which was accompanied by a reduction in fecal pH
      and presence of reducing sugars in the feces. This effect was reversed when
      calves were returned to the milk replacer diet at the end of the study. Diarrhea
      was accompanied by increased water consumption, which allowed the calves to
      maintain normal hydration status. These results suggest that calves are unable to
      properly digest the rice-derived carbohydrate, and this type of formula is not
      recommended for oral rehydration of calves.

PMID- 10935900
TI  - Bluetongue and persistent bovine viral diarrhea virus infection causing
      generalized edema in an adult bull.

PMID- 10935901
TI  - Localization of saponin-sterol complexes and lectin-binding sites during
      interaction of Toxoplasma gondii with host cells.
AB  - The attachment of tachyzoites of Toxoplasma gondii to the surface of host cells
      induces the formation of a vacuole known as the parasitophorous vacuole (PV). In
      the present study we used lectins labeled with either fluorescein or colloidal
      gold particles to follow the fate of lectin-binding sites on the host-cell
      surface during the process of parasite/host-cell interaction. The results
      obtained indicate that few, if any, lectin-binding sites are internalized
      together with the tachyzoites to make part of the PV membrane. However, these
      sites are internalized and observed in small vesicles that are seen close to the
      PV. We also used the freeze-fracture technique in cells treated with saponin,
      which reveals cholesterol-containing sites as easily identifiable elongated
      sulculi and depressions. Intramembranous particles, which represent membrane
      integral proteins, were seen in the membrane lining the PV. However, saponin
      cholesterol complexes were not observed in the membrane lining the PV, although
      they were seen in the parasite membranes. These observations, in association with
      data from previous studies, show that some, but not all, membrane components of
      the host cell contribute to the formation of the PV membrane.

PMID- 10935902
TI  - Entamoeba dispar, but not E. histolytica, detected in a colony of chimpanzees in
      Japan.
AB  - Chimpanzees (Pan troglodytes) residing in the Kumamoto Primate Research Park,
      Sanwa Kagaku Kenkyusho, were surveyed for the presence of intestinal parasites.
      Stool samples from 107 chimpanzees were examined by microscopy after formalin
      ether sedimentation. Of these animals, 100 were infected with at least 1 species
      of ameba. The positivity rates recorded were as follows: Entamoeba coli, 88%; E.
      histolytica/E. dispar, 48%; E. hartmanni, 15%; Iodamoeba buetschlii, 8%;
      Endolimax nana, 4%; and Entamoeba chattoni, 2%. Polymerase chain reaction (PCR)
      analysis to distinguish between E. histolytica and E. dispar was performed on
      these samples. E. dispar DNA was detected in 60 of 107 samples (56%), including 9
      that had been microscopically determined to be negative for E. histolytica/ E.
      dispar. In contrast, no E. histolytica DNA was detected in the 107 samples.
      Zymodeme analysis indicated that 10 isolates were E. dispar. When 104 chimpanzees
      were examined serologically for E. histolytica infection, 1 sample was scored as
      positive by indirect hemagglutination and another was found to be positive by an
      indirect fluorescent antibody test. However, both specimens were borderline
      positive and were clearly negative in other tests, suggesting that they might be
      false-positives. These results demonstrate that the pathogenic E. histolytica was
      absent in this colony, regardless of the high degree of prevalence of other
      amebas. For an accurate diagnosis, PCR analysis is recommended in addition to
      microscopic examination.

PMID- 10935903
TI  - SCID mice show a similar susceptibility to Angiostrongylus cantonensis as do wild
      type mice of the C.B-17 strain.
AB  - C.B-17-SCID/SCID (SCID) mice infected with Angiostrongylus cantonensis yielded a
      high percentage of worm recovery and did not show any body weight loss until day
      24 postinfection. Unexpectedly, C.B-17-+/+(+/+) mice also produced a similar worm
      burden containing well-developed worms. This is probably attributable to the
      observation that +/+ mice failed to induce eosinophilia in cerebrospinal fluid
      (CSF) despite their production of antigen-specific IgA and IgGI; +/+ mice have
      defective bone-marrow eosinopoiesis, which in turn results in reduced blood and
      CSF eosinophilia. Interleukin 5 (IL-5) production in +/+ mice is similar to that
      in BALB/c and C57BL/6 mice. However, bone-marrow eosinopoiesis in response to IL
      5 is markedly suppressed in +/+ mice. This is probably associated with impaired
      expression of common beta-chain mRNA in bone-marrow cells of +/+ mice, which
      leads to the failure of bone-marrow eosinopoiesis. Hence, +/+ mice may serve as a
      useful model for the elucidation of eosinophil production in the mouse and for
      determination of the relationship between parasite infection and the eosinophil.

PMID- 10935904
TI  - Distribution of Anisakis simplex in fish caught in the Ligurian Sea.
AB  - A total of 822 individuals of 5 fish species were sampled in the western coastal
      area of the Mediterranean Sea and examined for the presence of Anisakis simplex
      larvae in the body cavity, muscle, and viscera. A. simplex mean intensity (mI)
      and prevalence (Pr) values were very high in the common scad (Trachurus
      trachurus; Pr 80-100%, mI 19.3-36.8) and the blue scad (T. picturatus; Pr 80
      100%, mI 18.2-70.7), moderate in the blue whiting (Micromesistius poutassou), and
      low in the red mullet (Mullus barbatus) and the striped mullet (M. surmuletus).
      The larval burden was strongly related to host length in the common and blue
      scad.

PMID- 10935905
TI  - Influence of saturation deficit and temperature on Ixodes ricinus tick questing
      activity in a Lyme borreliosis-endemic area (Switzerland).
AB  - Questing Ixodes ricinus ticks were sampled monthly in a periurban mixed forest at
      Neuchatel, Switzerland, in 1996, 1997, and 1998. A total of 5,530 I. ricinus
      nymphs and 1,385 adults were collected. The emergence of questing tick
      populations in spring varied among years in relation to the air temperature. The
      monthly variation in questing nymph density was negatively correlated with the
      saturation deficit; there was a strong decrease in tick numbers in late spring
      and summer as soon as the saturation deficit increased. A variation in tick
      density in relation to the saturation deficit was also observed between years;
      the tick density was high when the saturation deficit was low during spring and
      summer (1997) and was low when the saturation deficit was high (1998). During the
      3-year study period, marked climatic differences among years highlighted the
      influence of temperature and saturation deficit on the phenology of ticks.

PMID- 10935906
TI  - Fasciola hepatica: lithogenic capacity in experimentally infested rats and
      chemical determination of the main stone components.
AB  - A study was done of the possible association between the development of common
      bile-duct stones and the presence of worms in rats experimentally infected with
      Fasciola hepatica. A total of 157 rats were individually infected with 20
      metacercariae, and another 40 animals served as controls. The rats were dissected
      at 100, 200, 300, and 400 days postinfection (p.i.). A significant association
      was observed between the observation of stones and the presence of F. hepatica
      adults. The global frequency of bile-duct lithiasis in the parasitized rats was
      22%, with a significantly lower incidence being observed in the younger group
      (100 days p.i.). Different analytical techniques were used to determine the main
      stone components. Energy-dispersive X-ray microanalysis showed calcium to be the
      main component in all cases (82-94%). Scanning electron microscopy, nuclear
      magnetic resonance ([1H]- and [13C]-NMR), and mass spectrometry revealed the
      predominance of palmitic (C-16) and stearic (C-18) acid.

PMID- 10935907
TI  - Ultrastructure of Hemolivia mariae gamonts in the blood of the lizard Tiliqua
      rugosa and their development to oocyst stage in the tick Amblyomma limbatum.
AB  - The ultrastructural features of the development of Hemolivia mariae from intra
      erythrocytic gamonts in their host, the Australian lizard Tiliqua rugosa, to
      oocysts containing sporokinetes in their vector, the tick Amblyomma limbatum, are
      described. Mature intra-erythrocytic gamonts, as well as gamonts ingested by the
      tick were encased in a thick (30 nm) capsule with distinct suture sites at each
      of the two apices. In the only image of a presumed syzygy, both partners were
      still encased. Further stages, the young and ongrowing oocysts, were bound by a
      membranous wall. Sporokinetes developed within the oocyst around a primordial
      crystalloid body. The fully differentiated sporokinetes, still resting within the
      oocyst wall, exhibited a very short conoid in the apical complex and were heavily
      loaded with crystalloid material.

PMID- 10935908
TI  - Influence of mechanical tail-detachment techniques of schistosome cercariae on
      the production, viability, and infectivity of resultant schistosomula: a
      comparative study.
AB  - Two decaudation methods used by Schistosoma mansoni cercariae for the production
      of schistosomula by in vitro transformation were comparatively tested. Both low
      pressure syringe passage and vortex mixing of the cercariae produced
      schistosomula of similar percentages of viability, and the levels of worm
      recovery following subcutaneous injection in mice were also comparable, though
      low. By all criteria tested, including simplicity and time requirement, the two
      methods are equally efficient and are well applicable for mass production of
      schistosomula.

PMID- 10935909
TI  - Blastocystis hominis: neutral red supravital staining and its application to in
      vitro drug sensitivity testing.
AB  - A simple in vitro drug sensitivity testing system for Blastocystis hominis
      clinical isolates was developed. Application of supravital staining by neutral
      red allowed quantitative viability assessment. Four xenic cultures, isolated from
      human sources, were grown in modified monophasic Robinson's medium and tested for
      sensitivities to nine available drugs. Assessment was done using the cell-count
      method from air-dried preparations after supravital staining with neutral red.
      Also, the light absorbence method was evaluated. Trimethoprim, metronidazole,
      quinacrine, tetracycline, paromomycin, and two new antiprotozoal drugs,
      nitazoxanide and deacetyl-nitazoxanide, showed cytostatic or cytocidal effects on
      all or some Blastocystis isolates. Chloroquine and sulphamethoxazole did not
      demonstrate any effect at the concentrations studied.

PMID- 10935910
TI  - Status and origin of Haemonchinae (Nematoda: Trichostrongylidae) in deer: a
      survey conducted in France from 1985 to 1998.
AB  - During our investigations on helminthofauna in roe deer (Capreolus capreolus) and
      red deer (Cervus elaphus) in France (1985-1998) we isolated nematodes not only of
      the genus Haemonchus Cobb, 1898 but also of the genus Ashworthius Le Roux 1930,
      both of which belong to the same subfamily of Haemonchinae. The prevalence of
      Ashworthius was 22% (65/294) in roe deer and 40% (10/25) in red deer. H.
      contortus was not found in red deer, whereas its prevalence was only 3% (9/294)
      in roe deer. These data contrast with those observed in other European countries.
      The presence of A. sidemi in red and roe deers in France suggests a case of
      parasitism imported via sika deer. A hypothesis of their spread is proposed.

PMID- 10935911
TI  - Biochemical characterization of mitogen-activated protein (MAP) kinase activity
      in Toxoplasma gondii.
AB  - Mitogen-activated protein (MAP) kinase or extracellular signal-regulated kinase
      (ERK) are activated by many extracellular stimuli. In this study, we investigated
      whether MAP kinase and tyrosine kinases were involved in transducing signals in
      Toxoplasma gondii. Using anti-phosphotyrosine and anti-active ERK antibodies, we
      identified several phosphorylated proteins in Toxoplasma. In particular,
      phosphorylation of a 47 kDa and a 43 kDa protein increased strongly after calcium
      influx. MAP kinase activity, caused by calcium influx, was determined using
      either a specific synthetic peptide, or an in gel kinase assay. Conversely,
      calcium chelators (BAPTA and EGTA) and a calcium channel blocker (nifedipine)
      inhibited this activation. Also, a specific inhibitor of MAP kinase kinase (PD
      098059) blocked MAP kinase activity. Three specific anti-MAP kinase antibodies
      recognized the 47 kDa and 43 kDa proteins, which were putatively identified as
      ERK1- and ERK2-homologs, respectively. These findings provide early evidence of
      signal transduction involving members of the MAP kinase family in T. gondii.

PMID- 10935912
TI  - Effect of cytochalasin D on the growth, encystation, and multinucleation of
      Entamoeba invadens.
AB  - The effect of cytochalasin D, a specific inhibitor of microfilaments, on the
      growth, encystation, and multinucleation of Entamoeba invadens was examined.
      Cytochalasin D blocked the growth of axenic E. invadens strain IP-1 in a dose
      dependent manner, which suggests that the drug is effective against this species
      of Entamoeba as well as against E. histolytica strain HM1: IMSS as previously
      demonstrated. Encystation of E. invadens as induced in vitro was also inhibited
      by cytochalasin D. This is the first evidence of the participation of
      microfilaments in the encystation process. Concentrations of cytochalasin D
      effective for the inhibition of encystation were lower than those effective for
      the inhibition of growth. Trophozoites grown with cytochalasin D became
      multinucleate; more than three nuclei per cell were observed in 71% of
      trophozoites grown in the presence of the drug as opposed to only 5% of those
      grown in the absence of the drug. Also, trophozoites grown with cytochalasin D
      produced multinucleate cysts following their transfer to encystation medium.
      Encystation with cytochalasin D was more strongly inhibited among trophozoites
      grown in the presence of the drug than among those grown in the absence of the
      drug. Also, encystation without cytochalasin D was less frequently observed among
      trophozoites grown in the presence of the drug than among those grown in the
      absence of the drug. Thus, the multinucleation of trophozoites induced by
      cytochalasin D had an inhibitory effect on their encystation.

PMID- 10935913
TI  - Interaction of antibodies with Entamoeba histolytica trophozoites from
      experimental amebic liver abscess: an immunocytochemical study.
AB  - Using immunocytochemical techniques, we studied the interaction of antibodies
      with Entamoeba histolytica trophozoites present during the development of amebic
      liver abscess. Hamsters were intrahepatically inoculated with HM1-IMSS axenic
      amebas and sacrificed at different days post-inoculation. IgG of rabbit anti-E.
      histolytica and IgG of rabbit anti-IgG of hamster were used, both labeled with
      peroxidase. With the rabbit anti-E. histolytica, all trophozoites present in
      hepatic lesions from 1-7 days post-inoculation were highly labeled. The IgG of
      rabbit anti-IgG of hamster intensively stained only those trophozoites present in
      lesions from 1-2 days post-inoculation. From day 3, the intensity and number of
      labeled trophozoites decreased progressively. The results suggest that the
      interaction between the amebas and the IgG of hamster is non-specific during the
      first 2 days. The absence of labeling in the chronic stages could be due to
      changes in the membrane antigens of the parasite or to alterations in the
      bloodstream around necrosis. Also, the anti-E. histolytica antibodies produced in
      the serum during the development of the hepatic disease are apparently incapable
      of reaching and interacting with the trophozoites present on the liver abscess.
      This can explain in part why antibodies do not have an important role in the
      defense of the host.

PMID- 10935914
TI  - Trichomonas vaginalis: analysis of a heat-inducible member of the cytosolic heat
      shock-protein 70 multigene family.
AB  - A 2253-nucleotide (nt) transcript for a Trichomonas vaginalis heat-shock protein
      70, TVCHSP70, has been isolated that encodes for a protein of 659 amino acids
      with a predicted molecular weight of 71.3 kDa. TVCHSP70 has a short (10-nt) 5'
      untranslated region (UTR), and the 263-nt 3' UTR is the longest reported for a
      Trichomonas peptide. Amino-acid sequence analysis and phylogenetic comparison
      identifies TVCHSP70 as a member of the heat-inducible cytoplasmic HSP70 gene
      family. Southern-blot data indicate that T. vaginalis contains at least four
      members of the cytoplasmic HSP70 gene family. Members of the TVCHSP70 family are
      expressed as 2.3-kb transcripts at low levels during 37 degrees C culture, and
      their expression is significantly up-regulated at 43 degrees C. Slot-blot
      analysis of seven T. vaginalis clinical isolates demonstrated a 3- to 44-fold up
      regulation of TVCHSP70 under conditions of heat shock (43 degrees C) or oxidative
      stress (500 microm H2O2) as compared with controls (37 degrees C).

PMID- 10935915
TI  - The minimal local-asperity hypothesis of early retinal lateral inhibition.
AB  - Recently we found that the theories related to information theory existent in the
      literature cannot explain the behavior of the extent of the lateral inhibition
      mediated by retinal horizontal cells as a function of background light intensity.
      These theories can explain the fall of the extent from intermediate to high
      intensities, but not its rise from dim to intermediate intensities. We propose an
      alternate hypothesis that accounts for the extent's bell-shape behavior. This
      hypothesis proposes that the lateral-inhibition adaptation in the early retina is
      part of a system to extract several image attributes, such as occlusion borders
      and contrast. To do so, this system would use prior probabilistic knowledge about
      the biological processing and relevant statistics in natural images. A key novel
      statistic used here is the probability of the presence of an occlusion border as
      a function of local contrast. Using this probabilistic knowledge, the retina
      would optimize the spatial profile of lateral inhibition to minimize attribute
      extraction error. The two significant errors that this minimization process must
      reduce are due to the quantal noise in photoreceptors and the straddling of
      occlusion borders by lateral inhibition.

PMID- 10935916
TI  - Multidimensional encoding strategy of spiking neurons.
AB  - Neural responses in sensory systems are typically triggered by a multitude of
      stimulus features. Using information theory, we study the encoding accuracy of a
      population of stochastically spiking neurons characterized by different tuning
      widths for the different features. The optimal encoding strategy for representing
      one feature most accurately consists of narrow tuning in the dimension to be
      encoded, to increase the single-neuron Fisher information, and broad tuning in
      all other dimensions, to increase the number of active neurons. Extremely narrow
      tuning without sufficient receptive field overlap will severely worsen the
      coding. This implies the existence of an optimal tuning width for the feature to
      be encoded. Empirically, only a subset of all stimulus features will normally be
      accessible. In this case, relative encoding errors can be calculated that yield a
      criterion for the function of a neural population based on the measured tuning
      curves.

PMID- 10935917
TI  - Synergy in a neural code.
AB  - We show that the information carried by compound events in neural spike trains
      patterns of spikes across time or across a population of cells-can be measured,
      independent of assumptions about what these patterns might represent. By
      comparing the information carried by a compound pattern with the information
      carried independently by its parts, we directly measure the synergy among these
      parts. We illustrate the use of these methods by applying them to experiments on
      the motion-sensitive neuron H1 of the fly's visual system, where we confirm that
      two spikes close together in time carry far more than twice the information
      carried by a single spike. We analyze the sources of this synergy and provide
      evidence that pairs of spikes close together in time may be especially important
      patterns in the code of H1.

PMID- 10935918
TI  - Increased synchrony with increase of a low-threshold calcium conductance in a
      model thalamic network: a phase-shift mechanism.
AB  - A computer model of a thalamic network was used in order to examine the effects
      of an isolated augmentation in a low-threshold calcium current. Such an isolated
      augmentation has been observed in the reticular thalamic (RE) nucleus of the
      genetic absence epilepsy rat from the Strasbourg (GAERS) model of absence
      epilepsy. An augmentation of the low-threshold calcium conductance in the RE
      neurons (gTs) of the model thalamic network was found to lead to an increase in
      the synchronized firing of the network. This supports the hypothesis that the
      isolated increase in gTs may be responsible for epileptic activity in the GAERS
      rat. The increase of gTs in the RE neurons led to a slight increase in the period
      of the isolated RE neuron firing. In contrast, the low-threshold spike of the RE
      neuron remained relatively unchanged by the increase of gTs. This suggests that
      the enhanced synchrony in the network was primarily due to a phase shift in the
      firing of the RE neurons with respect to the thalamocortical neurons. The ability
      of this phase-shift mechanism to lead to changes in synchrony was further
      examined using the model thalamic network. A similar increase in the period of RE
      neuron oscillations was obtained through an increase in the conductance of the
      calcium-mediated potassium channel. This change was once again found to increase
      synchronous firing in the network.

PMID- 10935919
TI  - Multispikes and synchronization in a large neural network with temporal delays.
AB  - Coherent rhythms in the gamma frequency range are ubiquitous in the nervous
      system and thought to be important in a variety of cognitive activities. Such
      rhythms are known to be able to synchronize with millisecond precision across
      distances with significant conduction delay; it is mysterious how this can
      operate in a setting in which cells receive many inputs over a range of time.
      Here we analyze a version of mechanism, previously proposed, that the
      synchronization in the CA1 region of the hippocampus depends on the firing of
      "doublets" by the interneurons. Using a network of local circuits that are
      arranged in a possibly disordered lattice, we determine the conditions on
      parameters for existence and stability of synchronous solutions in which the
      inhibitory interneurons fire single spikes, doublets, or triplets per cycle. We
      show that the synchronous solution is only marginally stable if the interneurons
      fire singlets. If they fire doublets, the synchronous state is asymptotically
      stable in a larger subset of parameter space than if they fire triplets. An
      unexpected finding is that a small amount of disorder in the lattice structure
      enlarges the parameter regime in which the doublet solution is stable. Synaptic
      noise reduces the regime in which the doublet configuration is stable, but only
      weakly.

PMID- 10935920
TI  - Synchrony in heterogeneous networks of spiking neurons.
AB  - The emergence of synchrony in the activity of large, heterogeneous networks of
      spiking neurons is investigated. We define the robustness of synchrony by the
      critical disorder at which the asynchronous state becomes linearly unstable. We
      show that at low firing rates, synchrony is more robust in excitatory networks
      than in inhibitory networks, but excitatory networks cannot display any synchrony
      when the average firing rate becomes too high. We introduce a new regime where
      all inputs, external and internal, are strong and have opposite effects that
      cancel each other when averaged. In this regime, the robustness of synchrony is
      strongly enhanced, and robust synchrony can be achieved at a high firing rate in
      inhibitory networks. On the other hand, in excitatory networks, synchrony remains
      limited in frequency due to the intrinsic instability of strong recurrent
      excitation.

PMID- 10935921
TI  - Dynamics of spiking neurons with electrical coupling.
AB  - We analyze the existence and stability of phase-locked states of neurons coupled
      electrically with gap junctions. We show that spike shape and size, along with
      driving current (which affects network frequency), play a large role in which
      phase-locked modes exist and are stable. Our theory makes predictions about
      biophysical models using spikes of different shapes, and we present simulations
      to confirm the predictions. We also analyze a large system of all-to-all coupled
      neurons and show that the splay-phase state can exist only for a certain range of
      frequencies.

PMID- 10935922
TI  - A model for fast analog computation based on unreliable synapses.
AB  - We investigate through theoretical analysis and computer simulations the
      consequences of unreliable synapses for fast analog computations in networks of
      spiking neurons, with analog variables encoded by the current firing activities
      of pools of spiking neurons. Our results suggest a possible functional role for
      the well-established unreliability of synaptic transmission on the network level.
      We also investigate computations on time series and Hebbian learning in this
      context of space-rate coding in networks of spiking neurons with unreliable
      synapses.

PMID- 10935923
TI  - Emergence of phase- and shift-invariant features by decomposition of natural
      images into independent feature subspaces.
AB  - Olshausen and Field (1996) applied the principle of independence maximization by
      sparse coding to extract features from natural images. This leads to the
      emergence of oriented linear filters that have simultaneous localization in space
      and in frequency, thus resembling Gabor functions and simple cell receptive
      fields. In this article, we show that the same principle of independence
      maximization can explain the emergence of phase- and shift-invariant features,
      similar to those found in complex cells. This new kind of emergence is obtained
      by maximizing the independence between norms of projections on linear subspaces
      (instead of the independence of simple linear filter outputs). The norms of the
      projections on such "independent feature subspaces" then indicate the values of
      invariant features.

PMID- 10935924
TI  - Tilt aftereffects in a self-organizing model of the primary visual cortex.
AB  - RF-LISSOM, a self-organizing model of laterally connected orientation maps in the
      primary visual cortex, was used to study the psychological phenomenon known as
      the tilt aftereffect. The same self-organizing processes that are responsible for
      the long-term development of the map are shown to result in tilt aftereffects
      over short timescales in the adult. The model permits simultaneous observation of
      large numbers of neurons and connections, making it possible to relate high-level
      phenomena to low-level events, which is difficult to do experimentally. The
      results give detailed computational support for the long-standing conjecture that
      the direct tilt aftereffect arises from adaptive lateral interactions between
      feature detectors. They also make a new prediction that the indirect effect
      results from the normalization of synaptic efficacies during this process. The
      model thus provides a unified computational explanation of self-organization and
      both the direct and indirect tilt aftereffect in the primary visual cortex.

PMID- 10935925
TI  - Glucose catabolism of Escherichia coli strains with increased activity and
      altered regulation of key glycolytic enzymes.
AB  - This study investigates the effect of overexpression of key glycolytic enzymes
      exhibiting either native or alternative allosteric regulation on glucose
      bioconversion by resting Escherichia coli cells previously engineered for ethanol
      production. Homologous and heterologous pyruvate kinases (Pyk) and
      phosphofructokinases (Pfk) were individually and simultaneously overexpressed.
      Overexpression of the E. coli Pfk led to a shift from ethanol to lactate
      formation (three-fold above the control level) while overexpression of Pyks
      accelerated lactate formation two-fold with less reduction in ethanol formation.
      Further increase in lactate formation (five-fold above the control level)
      resulted from overexpression of Pfk from Lactobacillus bulgaricus which, unlike
      the E. coli Pfk, is not allosterically regulated by either phosphoenolpyruvate or
      ADP. These effects on the carbon flux distribution were accompanied by
      significant changes in the intracellular concentrations of several glycolytic
      intermediates. Increased Pfk levels led primarily to reduced levels of hexose
      phosphates. Increased Pyk activity resulted in more complex changes which were
      different for overexpressed native Pyk and for overexpressed Bacillus
      stearothermophilus Pyk, which differs from E. coli Pyk in lacking activation by
      fructose 1,6-diphosphate, but is allosterically activated by AMP and ribose 5
      phosphate. Simultaneous overexpression of native Pfk and Pyk caused a Pfk
      overexpression-like phenotype with lower levels of hexose phosphates and further
      increased lactate formation (nine-fold above the control level). The flux data
      demonstrate that overexpression of even single enzymes early in a central pathway
      can increase the fluxes to a particular metabolic product, although it may not
      affect the glucose uptake rate.

PMID- 10935926
TI  - In vivo dynamics of the pentose phosphate pathway in Saccharomyces cerevisiae.
AB  - The in vivo dynamics of the pentose phosphate pathway has been studied with
      transient experiments in continuous culture of Saccharomyces cerevisiae. Rapid
      sampling was performed with a special sampling device after disturbing the steady
      state with a pulse of glucose. The time span of observation was 120 s after the
      pulse. During this short time period the dynamic effect of protein biosynthesis
      can be neglected. The metabolites of interest (glucose 6-phosphate, NADP, NADPH,
      6-phosphogluconate, and MgATP2-) we determined with enzymatic assays and HPLC.
      The experimental observations were then used for the identification of kinetic
      rate equations and parameters under in vivo conditions. In accordance with
      results from in vitro studies the in vivo diagnosis supports an ordered Bi-Bi
      mechanism with noncompetitive inhibition by MgATP2- for the enzyme glucose-6
      phosphate dehydrogenase. In the case of 6-phosphogluconate dehydrogenase an
      ordered Bi-Ter mechanism with a competitive inhibition by MgATP2- has been found.
      Because the MgATP2- concentration decreases abruptly after the pulse of glucose
      the inhibitory effect vanishes and the flux through the pentose phosphate pathway
      increases. This regulation phenomenon guarantees the balance of fluxes through
      glycolysis and pentose phosphate pathway during the dynamic time period.

PMID- 10935927
TI  - Redistribution of metabolic fluxes in Escherichia coli with fermentative lactate
      dehydrogenase overexpression and deletion.
AB  - Under anaerobic conditions, competition for pyruvate between the branch point
      enzymes pyruvate formate lyase (PFL, Km = 2 mM) and fermentative lactate
      dehydrogenase (LDH, Km = 7.2 mM) determines the partition of carbon flux. Two
      Escherichia coli mutant strains, one deficient in ackA, pta, and ldhA and the
      other overexpressing LDH, were constructed to systematically analyze the effects
      of these perturbations in the existing pathways on the redistribution of carbon
      fluxes. Deletion of the lactate and acetate synthesis pathways was detrimental to
      cell growth. Carbon flux is forced through ethanol and formate production
      pathways, resulting in a concomitant increase in those fluxes. In addition,
      overexpression of LDH simultaneously increases the common flux as well as the
      flux to the competing acetyl-CoA branch. Overexpression of lactate dehydrogenase
      (ldhA) in the parent strain increases the lactate synthesis rate from 0.19 to
      0.40 mmol/g-biomass-h when the LDH activities increases from 1.3 to 15.3 units.
      Even an increase of more than 10 times in the LDH activity fails to divert a
      large fraction of the carbon flux to lactate; the majority of the flux still
      channels through the acetyl-CoA branch. Overexpression of LDH in the parent
      strain simultaneously increases the common flux as well as the flux through the
      acetyl-CoA branch. Subsequently, the flux amplification factors (or deviation
      indices which can be related to the flux control coefficients) are positive for
      all three fluxes occurring at the pyruvate node.

PMID- 10935928
TI  - Classification and sensitivity analysis of a proposed primary metabolic reaction
      network for Streptomyces lividans.
AB  - Constructing a metabolic flux analysis model is in principle fairly
      straightforward. However, there are a number of mathematical pitfalls. First,
      dependent reactions are a recurring problem and, second, the choice of reactions
      to measure may not be straight-forward. A method for systematic identification of
      dependent reactions and a thorough reactions classification procedure is
      presented. A well-defined stoichiometric presentation can provide significant
      insight into metabolic control mechanisms. Two methods for analyzing the impact
      of perturbations in the measured fluxes on the remaining metabolism and the
      impact of changes in biomass composition on the calculated metabolic reactions is
      developed. A metabolic reaction network proposed for Streptomyces lividans is
      used as an example to demonstrate the outlined analysis. It is concluded that
      oxygen utilization has the highest influence on the pathway fluxes and that
      realistic perturbations in the biomass composition do not significantly alter the
      flux patterns.

PMID- 10935929
TI  - Quantification of intracellular metabolic fluxes from fractional enrichment and
      13C-13C coupling constraints on the isotopomer distribution in labeled biomass
      components.
AB  - A method for the quantification of intracellular metabolic flux distributions
      from steady-state mass balance constraints and from the constraints posed by the
      measured 13C labeling state of biomass components is presented. Two-dimensional
      NMR spectroscopy is used to analyze the labeling state of cell protein
      hydrolysate and cell wall components. No separation of the biomass hydrolysate is
      required to measure the degree of 13C-13C coupling and the fractional 13C
      enrichment in various carbon atom positions. A mixture of [1-13C]glucose and
      uniformly labeled [13C6]glucose is applied to make fractional 13C enrichment data
      and measurements of the degree of 13C-13C coupling informative with respect to
      the intracellular flux distribution. Simulation models that calculate the
      complete isotopomer distribution in biomass components on the basis of isotopomer
      mapping matrices are used for the estimation of intracellular fluxes by least
      squares minimization. The statistical quality of the estimated intracellular flux
      distributions is assessed by Monte Carlo methods. Principal component analysis is
      performed on the outcome of the Monte Carlo procedure to identify groups of
      fluxes that contribute major parts to the total variance in the multiple flux
      estimations. The methods described are applied to a steady-state culture of a
      glucoamylase-producing recombinant Aspergillus niger strain.

PMID- 10935930
TI  - Tolerance and specificity of recombinant 6-methylsalicyclic acid synthase.
AB  - BACKGROUND: 6-Methylsalicylic acid synthase (MSAS), a fungal polyketide synthase
      from Penicillium patulum, is perhaps the simplest polyketide synthase that
      embodies several hallmarks of this family of multifunctional enzymes--a large
      multidomain protein, a high degree of specificity toward acetyl-CoA and malonyl
      CoA substrates, chain length control, and regiospecific ketoreduction. MSAS has
      recently been functionally expressed in Escherichia coli and Saccharomyces
      cerevisiae, leading to the engineered biosynthesis of 6-methylsalicylic acid in
      these hosts. These developments have set the stage for detailed mechanistic
      studies of this model system. RESULTS: A three--step purification procedure was
      developed to obtain >95% pure MSAS from extracts of E. coli. As reported earlier
      for the enzyme isolated from P. patulum, the recombinant enzyme produced 6
      methylsalicylic acid (a reduced tetraketide) in the presence of acetyl-CoA,
      malonyl-CoA, and NADPH, but triacetic acid lactone (an unreduced triketide) in
      the absence of NADPH. Consistent with this observation, point mutations in the
      highly conserved nucleotide-binding motif of the ketoreductase domain also led to
      production of triacetic acid lactone in vivo. The enzyme showed some tolerance
      toward nonnatural primer units including propionyl- and butyryl-CoA, but was
      incapable of incorporating extender units from (R, S)-methylmalonyl-CoA.
      Interestingly, MSAS readily accepted the N-acetylcysteamine (NAC) analog of
      malonyl-CoA as a substrate. CONCLUSIONS: NAC thioesters are simple, cost
      effective analogs of CoA thioester substrates, and therefore provide a facile
      strategy for probing the molecular recognition features of polyketide synthases
      using unnatural building blocks. The ability to produce 4-hydroxy-6-methyl-2
      pyrone in both E. coli and yeast illustrates the feasibility of metabolic
      engineering of these hosts to produce unnatural polyketides. Finally, the
      abundant source of recombinant MSAS described here provides an opportunity to
      study this fascinating model system using a combination of structural,
      mechanistic, and mutagenesis approaches.

PMID- 10935931
TI  - Engineering a living cell to desired metabolite concentrations and fluxes:
      pathways with multifunctional enzymes.
AB  - With molecular genetics enabling modulation of the concentrations of cellular
      enzymes, metabolic engineering becomes limited by the question of which
      modulations of the enzyme concentrations are required to bring about a desired
      pattern of cellular metabolism. In an earlier paper (Kholodenko et al. (1998).
      Biotechnol. Bioeng. 59, 239-247) we derived a method to determine the required
      modulations. This method, however, cannot be immediately applied to cellular
      pathways with enzymes catalyzing more than one step in metabolism
      (multifunctional enzymes). In the present paper we show to which extent the
      presence of multifunctional enzymes limits biotechological ambitions, which one
      might otherwise pursue in vain. In particular, it is impossible to change the
      concentration of a single intermediate and leave the rest of metabolism
      unperturbed if that intermediate interacts directly with a multifunctional
      enzyme. The analytical machinery of Metabolic Control Analysis is used to relate
      the desired and ensuing changes in the metabolic pattern. An explicit solution to
      this problem of engineering metabolism is then given in the form of a single
      matrix equation.

PMID- 10935932
TI  - Metabolic modeling of Saccharomyces cerevisiae using the optimal control of
      homeostasis: a cybernetic model definition.
AB  - A model is presented to describe the observed behavior of microorganisms that aim
      at metabolic homeostasis while growing and adapting to their environment in an
      optimal way. The cellular metabolism is seen as a network with a multiple
      controller system with both feedback and feedforward control, i.e., a model based
      on a dynamic optimal metabolic control. The dynamic network consists of
      aggregated pathways, each having a control setpoint for the metabolic states at a
      given growth rate. This set of strategies of the cell forms a true cybernetic
      model with a minimal number of assumptions. The cellular strategies and
      constraints were derived from metabolic flux analysis using an identified,
      biochemically relevant, stoichiometry matrix derived from experimental data on
      the cellular composition of continuous cultures of Saccharomyces cerevisiae.
      Based on these data a cybernetic model was developed to study its dynamic
      behavior. The growth rate of the cell is determined by the structural compounds
      and fluxes of compounds related to central metabolism. In contrast to many other
      cybernetic models, the minimal model does not consist of any assumed internal
      kinetic parameters or interactions. This necessitates the use of a stepwise
      integration with an optimization of the fluxes at every time interval. Some
      examples of the behavior of this model are given with respect to steady states
      and pulse responses. This model is very suitable for describing
      semiquantitatively dynamics of global cellular metabolism and may form a useful
      framework for including structured and more detailed kinetic models.

PMID- 10935933
TI  - Construction and characterization of an oxalic acid nonproducing strain of
      Aspergillus niger.
AB  - Aspergillus niger produces oxalic acid as a by-product which causes problems with
      downstream processing of industrial enzymes. To overcome this problem the oah
      gene encoding oxaloacetate hydrolase (EC 3.7.1.1) was disrupted in a glucoamylase
      producing strain of A. niger and the resulting strain was incapable of producing
      oxalic acid. The strain with the disrupted gene was compared with the wild-type
      strain producing oxalic acid in batch cultivations. The specific growth rate of
      both strains was 0.20 h(-1). The citric acid yields were identical, but the
      glucoamylase yield was only 50% in the disruptant compared with the wild-type
      strain. Batch experiments with 13C-labeled glucose as substrate were carried out
      to determine the metabolic fluxes through the central metabolism. The two strains
      had almost identical metabolic fluxes, which suggested that it was possible to
      disrupt the oah gene without pleiotropic consequences. The flux through the
      pentose phosphate pathway was around 60% of the glucose uptake for both strains,
      which suggested that a sufficient supply of NADPH was available for biosynthesis.

PMID- 10935934
TI  - Biocatalysis for pharmaceuticals--status and prospects for a key technology.
AB  - In reviewing how biocatalysis can be applied to improve chiral synthesis for
      pharmaceuticals it becomes clear that there will be many opportunities using a
      simple enzyme system but that many of the more useful applications will require
      the whole cell because of the requirement for cofactors. An assessment is made of
      the opportunities to apply metabolic engineering to construct de novo metabolic
      pathways for the biosynthesis of useful advanced intermediates and a conceptual
      example is provided for the biosynthesis of cis-aminoindanol. We predict that in
      the future novel pathways will be assembled for a one-step biosynthesis of many
      semisynthetic natural products.

PMID- 10935935
TI  - Dynamic optimal control of homeostasis: an integrative system approach for
      modeling of the central nitrogen metabolism in Saccharomyces cerevisiae.
AB  - The theory of dynamic optimal metabolic control (DOMC), as developed by Giuseppin
      and Van Riel (Metab. Eng., 2000), is applied to model the central nitrogen
      metabolism (CNM) in Saccharomyces cerevisiae. The CNM represents a typical system
      encountered in advanced metabolic engineering. The CNM is the source of the
      cellular amino acids and proteins, including flavors and potentially valuable
      biomolecules; therefore, it is also of industrial interest. In the DOMC approach
      the cell is regarded as an optimally controlled system. Given the metabolic
      genotype, the cell faces a control problem to maintain an optimal flux
      distribution in a changing environment. The regulation is based on strategies and
      balances feedback control of homeostasis and feedforward regulation for
      adaptation. The DOMC approach is an integrative, holistic approach, not based on
      mechanistic descriptions and (therefore) not biased by the variation present in
      biochemical and molecular biological data. It is an effective tool to structure
      the rapidly increasing amount of data on the function of genes and pathways. The
      DOMC model is used successfully to predict the responses of pulses of ammonia and
      glutamine to nitrogen-limited continuous cultures of a wild-type strain and a
      glutamine synthetase-negative mutant. The simulation results are validated with
      experimental data.

PMID- 10935936
TI  - Optimization of ethanol production in Saccharomyces cerevisiae by metabolic
      engineering of the ammonium assimilation.
AB  - Ethanol is still one of the most important products originating from the
      biotechnological industry with respect to both value and amount. In addition to
      ethanol, a number of byproducts are formed during an anaerobic fermentation of
      Saccharomyces cerevisiae. One of the most important of these compounds, glycerol,
      is produced by yeast to reoxidize NADH, formed in synthesis of biomass and
      secondary fermentation products, to NAD+. The purpose of this study was to
      evaluate whether a reduced formation of surplus NADH and an increased consumption
      of ATP in biosynthesis would result in a decreased glycerol yield and an
      increased ethanol yield in anaerobic cultivations of S. cerevisiae. A yeast
      strain was constructed in which GLN1, encoding glutamine synthetase, and GLT1,
      encoding glutamate synthase, were overexpressed, and GDH1, encoding the NADPH
      dependent glutamate dehydrogenase, was deleted. Hereby the normal NADPH-consuming
      synthesis of glutamate from ammonium and 2-oxoglutarate was substituted by a new
      pathway in which ATP and NADH were consumed. The resulting strain TN19 (gdh1-A1
      PGK1p-GLT1 PGK1p-GLN1) had a 10% higher ethanol yield and a 38% lower glycerol
      yield compared to the wild type in anaerobic batch fermentations. The maximum
      specific growth rate of strain TN19 was slightly lower than the wild-type value,
      but earlier results suggest that this can be circumvented by increasing the
      specific activities of Gln1p and Glt1p even more. Thus, the results verify the
      proposed concept of increasing the ethanol yield in S. cerevisiae by metabolic
      engineering of pathways involved in biomass synthesis.

PMID- 10935937
TI  - Investigation of an acute chemical incident: exposure to fluorinated
      hydrocarbons.
AB  - OBJECTIVES: To assess whether attendance at the site after an incident in a sewer
      was associated with symptoms in emergency personnel and whether the prevalence of
      symptoms was associated with estimated levels of exposure to any chemical hazard.
      METHODS: Symptoms experienced by people attending an incident involving two dead
      sewer workers suggested the presence of a chemical hazard, before environmental
      sampling confirmed any toxic agent. Self reported symptoms, estimated exposures,
      and biomarkers of exposure for likely agents from all 254 people who attended the
      incident and a referent occupational group matching the 83 emergency personnel
      who went to the Accident and Emergency department (A and E) in the first 48 hours
      were recorded. The prevalence of symptoms and concentrations of creatine
      phosphokinase in serum of the 83 early patients at A and E were compared with
      their referent occupational group. In all workers who attended the incident, the
      trends in symptom prevalences and concentrations of creatine phosphokinase in
      serum were examined by distance from the site and predefined exposure category.
      RESULTS: Among all workers who attended the incident, symptoms of shortness of
      breath and sore throat were significantly associated with indirect estimates of
      exposure but not associated with concentrations of creatine phosphokinase. Freon
      was detected in two blood samples. The early patients at A and E reported more
      symptoms than their matched reference group and their median concentrations of
      creatine phosphokinase were higher. CONCLUSIONS: The association between symptoms
      and concentrations of creatine phosphokinase with attendance at the site
      indicated the presence of a continuing hazard at the site and led to extra
      precautions being taken. Comparison values from the referent occupational group
      prevented unnecessary medical follow up.

PMID- 10935938
TI  - Impairment of colour vision in workers exposed to organic solvents.
AB  - OBJECTIVES: To investigate loss of colour vision related to exposure to solvents
      and the role of three enzyme polymorphisms in modifying the risk in exposed
      workers. METHODS: A sample was studied of 68 male dockyard workers and 42 male
      community controls with and without neuropsychological symptoms from a previous
      cross sectional study. Indices of cumulative and intensity based exposure to
      solvents were calculated for all subjects. Alcohol, drug, and smoking histories
      were obtained. Colour vision was tested by Lanthony D15d colour vision test.
      Genotype of glutathione S-transferase M1 and T1 and N-acetyltransferase 2
      polymorphisms were determined. RESULTS: The relation between impairment of colour
      vision and exposure to solvents was investigated with multiple regression
      techniques. Increasing annual exposure to solvents was significantly associated
      with reduced colour vision (p=0.029). Impairment of colour vision was not
      associated with neuropsychological symptoms as measured by the Q16 solvent
      symptom questionnaire. No significant association was found between acquired
      impairment of colour vision and genetic polymorphisms when GSTM1, GSTT1 or NAT2
      phenotypes were included in the analyses. CONCLUSIONS: Exposure to mixed solvents
      is associated with impairment in colour vision, the risk increases with
      increasing exposure. The risk of impairment of colour vision was not altered in
      this study by the presence of different GSTM1, GSTT1 or NAT2 polymorphisms.

PMID- 10935939
TI  - Vibration perception thresholds in workers with long term exposure to lead.
AB  - OBJECTIVES: To evaluate the impact of long term occupational exposure to lead on
      function of the peripheral nervous system as reflected by vibration perception
      threshold (VPT), measured with a portable vibrameter. METHODS: 217 Workers in a
      lead battery factory were required to have an annual blood lead measurement
      during each of the 5 years preceding this study. All were invited to take the VPT
      test. A total of 206 workers were studied. The associations were analysed between
      VPTs and current blood lead concentration, mean concentration of blood lead over
      the past 5 years, maximum blood lead concentration during the past 5 years, index
      of cumulative blood lead (ICL), time weighted index of cumulative blood lead
      (TWICL), and percentage of lifespan spent at work in the plant, as well as the
      other potential confounders. Ordinary multiple regressions, generalised additive
      models, and hockey stick regression analyses were used to explore the potential
      existence of a threshold effect of blood lead variables on VPT. RESULTS: VPT at a
      frequency of 220 Hz ranged from 6 to 100 (10(-2) g, or 0.098 m/s(2)) with a mean
      (SD) of 19.8 (14.2) for the feet and from 4 to 43 with a mean (SD) of 10.2 (6.1)
      for the hands. The five variables of exposure to lead were all significantly
      correlated with VPT of the feet but not the hands. In multiple linear regression
      analyses, the mean of the blood lead concentrations and the TWICL were
      significantly associated with VPT of the feet. The relation between VPT of the
      feet and mean blood lead was shown to be a J shaped curve with a generalised
      additive model and local smoothing technique. In the hockey stick regression,
      evidence was found of a threshold effect at a mean blood lead concentration of 31
      microgram/dl. Above this threshold it was estimated that each increase of 1
      microgram/dl mean blood lead over 5 years would increase VPT of the feet by 0.29
      (10(-2) g) or 0.028 m/s(2) (at a frequency of 220 Hz) with other potential
      confounders held constant. CONCLUSION: This study suggests that measurement of
      vibration sensory threshold is a relatively effective tool for detecting lead
      neuropathy in field studies, and that lead might cause sensory neuropathy with an
      effect threshold corresponding to a 5 year mean blood lead concentration of 31
      microgram/dl.

PMID- 10935940
TI  - Updated mortality among diverse operating segments of a petroleum company.
AB  - OBJECTIVES: To update mortality for 34 560 employees from diverse operating
      segments of a Canadian petroleum company; and to investigate potential relations
      with occupational factors. METHODS: Employees from 1964-83 were linked to the
      Canadian mortality data base to provide 11 years additional follow up. There were
      6760 deaths and 750 683 person-years of follow up compared with 3909 and 428 190,
      respectively, in the earlier study. Analyses used standardised mortality ratios
      (SMRs) to compare worker cause specific mortality with the Canadian general
      population. Duration of employment and latency analyses were performed for causes
      previously found to be increased in this and other petroleum cohorts, as well as
      any findings of interest. RESULTS: For the period 1964-94, employees experienced
      significantly low overall mortality (SMR=0.86 men, SMR=0.80 women). Kidney
      cancer, which has been increased in some studies of petroleum workers, was not
      increased. Acute non-lymphocytic leukaemia in exposed operating segments was
      consistent with the expected or only slightly, non-significantly increased. The
      most notable finding was increased deaths from mesothelioma among refinery and
      petrochemical workers (SMR 8.68; 95% confidence interval (95% CI) 5.51 to 13.03),
      most of whom were long term employees in jobs with presumed exposure to asbestos
      (mechanical and pipefitters). Deaths from multiple myeloma among marketing and
      distribution workers, which were previously increased, remained increased (SMR
      2.08; 95% CI 0.95 to 3.95) in the update period 1984-94; however, there was no
      clear pattern by duration of employment or latency. Aortic aneurysms, which also
      were previously significantly increased among marketing and distribution workers
      approached the expected in the update period (SMR 1.18; 95% CI 0. 65-1.98).
      Analyses by duration of employment showed suggestive trends for aortic aneurysms,
      but earlier studies of this cohort have not found a relation between aortic
      aneurysms and exposure to hydrocarbons. CONCLUSION: The additional 2851 deaths
      and 322 493 person-years of follow up strengthened the assessment of mortality
      patterns relative to occupational factors. With the exception of mesothelioma, no
      clear work related increases in disease were identified.

PMID- 10935942
TI  - Sickness absence and early retirement on health grounds in the construction
      industry in Ireland.
AB  - OBJECTIVE: To establish a detailed pattern of the nature and extent of illnesses
      and injuries among construction workers in Ireland which cause temporary absence
      from work, and to identify diseases and disabilities which lead to premature
      retirement from the industry on health grounds. METHODS: The population base for
      the study consisted of construction workers who were members of the Construction
      Federation operatives pension and sick pay scheme. Records of sickness absence
      since 1981, stored on computer disks, and records of early retirement on health
      grounds since 1972, stored on microfiche film, were examined. Pertinent data were
      extracted and transferred to a database; after cleaning and the exclusion of
      unvalidated data, records of 28 792 absences and 3098 records of early retirement
      were available for analysis. Data were analysed with Access 97 and Epi Info.
      RESULTS: Over the period of the study the mean annual absences were 7.8/100
      workers. Three quarters of absences were among younger workers; however, the rate
      of absence increased with age, as did the mean duration of absence. Injury was
      the most frequent reason for absence, followed by infectious disease, then
      musculoskeletal disorders. The mean annual rate of early retirement on health
      grounds was 5.3/1000 workers. The median age at retirement was 58 years.
      Cardiovascular disease and musculoskeletal disorders each accounted for nearly
      one third of the conditions leading to permanent disability on the grounds of
      which early retirement was granted. During the period of the study, over 677 000
      working days were lost due to sickness absence, and over 24 000 potential years
      of working lives were lost due to early retirement on health grounds.
      CONCLUSIONS: The study has shown patterns of sickness absence and early
      retirement on health grounds in the Irish construction industry which will
      contribute to the further development of health promotion strategies for
      construction workers.

PMID- 10935941
TI  - Incidence of lymphohaematopoietic malignancies in a petrochemical industry
      cohort: 1983-94 follow up.
AB  - OBJECTIVES: In response to a previous finding of increased mortality from
      lymphohaematopoietic (LH) malignancies, this study examines incidence of LH
      malignancy in a petrochemical industry cohort. Emphasis is on chronic lymphocytic
      leukaemia (CLL) and on comparisons by period of first employment. METHOD: The
      study cohort consists of 8942 employees who were active in the period 1970-92 and
      alive on 31 December 1982. Record linkage with the Louisiana tumour registry
      (LTR) provided information on cancer for cases occurring between 1983 and 1994.
      Standardised incidence ratios (SIR), with the south Louisiana population as a
      comparison, were computed for all cancers, all LH malignancies and specific LH
      subtypes. Analyses were conducted for sex and race categories, and by period of
      first employment, job type, duration of employment, and latency. RESULTS: 672
      Cases of cancer were identified, including 59 LH malignancies. Women (n=1169) had
      an overall cancer SIR below unity and four LH malignancies versus 2.28 expected.
      Among the 7773 men, those first employed before 1950 had no overall cancer
      excess, a significant 1.4-fold increase in overall LH malignancies (43 observed
      versus 30.78 expected), and four CLL cases versus 3.27 expected. Findings for men
      first employed after 1950 are based on fewer cases, but there was no indication
      of excesses of overall cancer or LH malignancy. Numbers were too small in the
      group first employed after 1950 for meaningful analysis of LH malignancy subtypes
      such as CLL (one case). CONCLUSION: These findings do not suggest a continuing
      excess of CLL but do suggest a small increase in incidence of overall LH
      malignancy for workers first employed before 1950. This may reflect associations
      with earlier workplace conditions, although work related patterns are mixed.
      Interpretation is limited by the diverse group of diseases within LH
      malignancies, and the lack of control for non-work factors other than sex, age,
      race, and period of diagnosis. This study has a major advantage of more complete
      and reliable cancer ascertainment compared with the mortality investigation, and
      shows the feasibility and benefits of using cancer registry incidence data in an
      occupational cohort study.

PMID- 10935943
TI  - Occupational risk of infection by varicella zoster virus in Belgian healthcare
      workers: a seroprevalence study.
AB  - OBJECTIVES: To assess the prevalence of varicella zoster virus (VZV) antibodies
      in Flemish (Belgian) healthcare workers, to investigate the association between
      seronegativity and selected variables, and to assess the reliability of recall
      about disease as a predictor of immunity. METHODS: A seroprevalence study of VZV
      antibodies (IgG) was conducted among a systematic sample of 4923 employees in
      various professional groups, employed in 22 hospitals in Flanders and Brussels
      (Belgium). Information about sex, age, department, job, and years of employment,
      the country of origin, and history of varicella was obtained. The presence of VZV
      antibodies was investigated with the enzyme linked immunosorbent assay (ELISA),
      Enzygnost anti VZV / IgG (Dade Behring, Marburg, Germany). Statistical analysis
      was performed by calculating prevalences and prevalence ratios (PRs) and their
      95% confidence intervals (95% CIs). Sensitivity, specificity, and positive and
      negative predictive values (PPV and NPV) of the recalled history were determined.
      RESULTS: The prevalence of VZV seropositivity in Flemish healthcare workers was
      98.5% (95% CI 98.1 to 98.8). Seronegativity was significantly associated with age
      and job, increasing with both older and younger age. The prevalence of
      seronegative workers was significantly less in nursing staff than non-nursing
      staff. There was no significant difference for sex and years of employment. The
      PPV and NPV of recalled history were 98.9% and 3.4%. Sensitivity and specificity
      were 83% and 38.9%. CONCLUSION: The prevalence of VZV seropositivity was very
      high in this sample of Flemish healthcare workers. Because of this low overall
      susceptibility, VZV infection seems not to be an important occupational risk
      among healthcare workers in Flanders. The increasing seronegativity above the age
      of 45 is possibly due to a loss of detectable antibodies. A positive history of
      varicella was a good predictor of immunity, but a negative history had no value
      as a predictor of susceptibility in adults.

PMID- 10935944
TI  - Building sickness syndrome in healthy and unhealthy buildings: an epidemiological
      and environmental assessment with cluster analysis.
AB  - OBJECTIVES: Building sickness syndrome remains poorly understood. Aetiological
      factors range from temperature, humidity, and air movement to internal
      pollutants, dust, lighting, and noise factors. The reported study was designed to
      investigate whether relations between symptoms of sick building syndrome and
      measured environmental factors existed within state of the art air conditioned
      buildings with satisfactory maintenance programmes expected to provide a healthy
      indoor environment. METHODS: Five buildings were studied, three of which were
      state of the art air conditioned buildings. One was a naturally ventilated
      control building and one a previously studied and known sick building. A
      questionnaire was administered to the study population to measure the presence of
      building related symptoms. This was followed by a detailed environmental survey
      in identified high and low symptom areas within each building. These areas were
      compared for their environmental performance. RESULTS: Two of the air conditioned
      buildings performed well with a low prevalence of building related symptoms. Both
      of these buildings out performed the naturally ventilated building for the low
      number of symptoms and in many of the environmental measures. One building (C),
      expected to perform well from a design viewpoint had a high prevalence of
      symptoms and behaved in a similar manner to the known sick building.
      Environmental indices associated with symptoms varied from building to building.
      Consistent associations between environmental variables were found for
      particulates (itchy eyes, dry throat, headache, and lethargy) across all
      buildings. There were persisting relations between particulates and symptoms
      (headache, lethargy, and dry skin) even in the building with the lowest level of
      symptoms and of measured airborne particulates (building B). There were also
      consistent findings for noise variables with low frequency noise being directly
      associated with symptoms (stuffy nose, itchy eyes, and dry skin) and higher
      frequency noise being relatively protective across all buildings. CONCLUSIONS:
      This is the first epidemiological study of expected state of the art, air
      conditioned buildings. These buildings can produce an internal environment better
      than that of naturally ventilated buildings for both reported symptoms and
      environmental variables. The factors associated with symptoms varied widely
      across the different buildings studied although consistent associations for
      symptoms were found with increased exposure to particulates and low frequency
      noise.

PMID- 10935946
TI  - Suicide in the farming community: methods used and contact with health services.
AB  - Farmers have a high rate of suicide (1% of suicides in England and Wales). This
      study sought to test whether farmers would be less likely to have been in contact
      with primary or mental health services before death due to their reluctance to
      seek help. The study also sought to identify other characteristics that
      differentiated suicide among male farmers from other professional groups. A
      retrospective case-control design was used comparing male farmers with an age and
      sex matched control group. Cases were all members of the farming community within
      the Exeter Health District on whom suicide or open verdict had been recorded
      between 1979 and 1994. 63 Cases were identified and entered into the study.
      Controls were non-farmers with the same verdict who were matched for age (5 year
      age bands) sex and social class. Farmers were significantly more likely to use
      firearms to kill themselves (42% of farmers v 11% controls). They were less
      likely to use a car exhaust or to die by poisoning (9% farmers v 50% controls).
      Farmers were significantly less likely to leave a suicide note (21% farmers v 41%
      controls). There was no significant difference between farmers and controls for
      numbers in contact with their general practitioner or mental health services in
      the 3 months before death. There may be some differences in help seeking
      behaviour between farmers and the general population as over 30% of farmers
      presented with exclusively physical symptoms. General practitioners should
      consider depressive and suicidal intention in farmers presenting with physical
      problems. When depression is diagnosed consideration should be given to the
      temporary removal of firearms as the high rate of suicide in the farming
      community may be strongly influenced by access to means.

PMID- 10935945
TI  - Development of an asthma specific job exposure matrix and its application in the
      epidemiological study of genetics and environment in asthma (EGEA).
AB  - OBJECTIVES: To develop a method suitable for estimating exposure risks in
      population studies of asthma from job titles and international codes, by
      combining a new job exposure matrix (JEM) with the expert judgement approach. The
      method was applied in the French epidemiological study of the genetics and
      environment in asthma (EGEA). METHODS: The JEM contains 22 exposure groups
      including 18 high risk groups based on known risk factors for occupational
      asthma, divided into high molecular weight agents, low molecular weight agents,
      and mixed environments. After applying the JEM to job codes, exposure estimates
      for each subject were re-evaluated by examining job title texts. Three high risk
      exposure estimates for asthma were compared: firstly, applying the JEM to
      original codes (from different coders in each study centre); secondly, applying
      the JEM to revised codes (from one experienced coder); and thirdly, after
      reviewing JEM exposure estimates in the light of job title texts. RESULTS: The
      study comprised 173 cases with asthma and 285 controls (age 18-65). Odds ratios
      (ORs) for asthma for high risk jobs were 1.0 (95% confidence interval (95% CI)
      0.6 to 1.7), applying the JEM to original codes; 1.4 (95% CI 0.8 to 2.3),
      applying the JEM to revised codes; and 1.7 (95% CI 1.1 to 2.7), applying the JEM
      and subsequently re-evaluating exposure estimates from job title texts. Asthma
      ORs were 1.4 (95% CI 0.6 to 2.9) for high molecular weight agents, 2.3 (95% CI
      1.2 to 4.4) for low molecular weight agents, and 2.1 (95% CI 0.9 to 5.2) for
      mixed environments. CONCLUSIONS: This asthma JEM, when enhanced by expert re
      evaluation of exposure estimates from job title texts, may be a useful tool in
      general population studies of asthma. In this study, a 1.7-fold increase in
      prevalence odds of high risk exposures was found among asthmatic workers compared
      with controls, with risk magnitude varying for different classes of exposure.

PMID- 10935947
TI  - Evaluation of a postgraduate educational programme for occupational physicians on
      work rehabilitation guidelines for patients with low back pain.
AB  - OBJECTIVES: The postgraduate educational programme for occupational physicians on
      guidelines for work rehabilitation of patients with low back pain was evaluated
      as to what extent did knowledge of the guidelines increase, and did the workers
      improve their performance at work. METHODS: An experimental group (n=25) attended
      an educational programme and a reference group did so (n=20) 6 months later.
      Knowledge and performance were assessed for both groups, before and after
      education of the experimental group. Knowledge was assessed for the reference
      group after education. RESULTS: Knowledge increased significantly more in the
      experimental group. The reference group's score increased further after
      education. The experimental group's adjusted gain score for performance
      indicators was significantly positive. Analysis of covariance also showed a
      significant effect for the experimental group for increased performance score.
      CONCLUSIONS: The educational programme improved the quality of care because
      knowledge and performance of occupational physicians improved and complied better
      with practice guidelines.

PMID- 10935948
TI  - In response

PMID- 10935949
TI  - Eruption guidance appliance effects.

PMID- 10935950
TI  - Ideal treatment results require more than good luck.

PMID- 10935951
TI  - Second opinions, and becoming a care manager.
AB  - After an unsuccessful period of orthodontic treatment (by another provider),
      state-of-the-art methods are used to gain a patient's trust. Diagnostic set-ups
      and digital imaging techniques help the patient feel confident enough to accept a
      comprehensive multidisciplinary treatment plan.

PMID- 10935953
TI  - Commentary

PMID- 10935952
TI  - Patients' own reasons and patient-perceived recommendations for orthognathic
      surgery.
AB  - In an attempt to learn more about patients' decision-making processes, an
      analysis was performed to examine patients' reasons for undergoing orthognathic
      surgery and their understanding of the reasons surgery was recommended. Before
      surgery, 105 females and 38 males completed an open-ended questionnaire in which
      they listed their reasons for choosing orthognathic surgery and their perceptions
      of their orthodontists' recommendations. Three raters classified the responses
      into 7 categories: esthetics, psychosocial, functional, TMJ/pain, authority,
      prevention, and other. Rater agreement ranged from a kappa of.55 to 1.00.
      Patients reported undergoing orthognathic surgery primarily for esthetic,
      functional, and TMJ improvements, 71%, 47%, and 28%, respectively. Females
      reported more TMJ-related reasons than males (P <.05). Patients reporting
      function (P <. 05), TMJ (P <.05), and prevention of future problems (P <.05) were
      older than patients not reporting these reasons. Mexican American patients
      indicated more psychosocial reasons (P <.05) than European Americans. Patients
      understood that orthognathic surgery was recommended primarily for esthetic,
      functional, and TMJ improvements, 52%, 44%, and 18%, respectively. Males reported
      receiving more preventative recommendations (23%) than females (10%). Mexican
      American patients reported receiving more psychosocial recommendations (P <.05)
      than European Americans. Agreement between each paired patient/patient-perceived
      reason was highest for TMJ problems (kappa = 0.588). In conclusion, patients
      underwent orthognathic surgery to improve esthetic, functional and TMJ problems
      and interpreted orthodontists' recommendations for similar reasons. On a case-to
      case basis, agreement between patient and orthodontist-represented reasons was
      modest, suggesting differences between patients' own reasons and their
      perceptions of orthodontists' recommendations.

PMID- 10935954
TI  - Class II correction in patients treated with class II elastics and with fixed
      functional appliances: a comparative study.
AB  - The aim of the present study was to evaluate quantitatively the skeletal and
      dental changes contributing to Class II corrections in subjects treated with
      Class II elastics (Begg technique) compared with subjects treated with fixed
      functional appliances (Herbst appliance). Thirty-six male patients with Class II,
      Division 1 malocclusions whose treatment had not included extraction were
      investigated. Eighteen were treated with the Begg technique, and eighteen were
      treated with Herbst appliance for an average period of 1.3 and 0.5 years,
      respectively. Lateral radiographs in habitual occlusion were taken at the start
      of treatment and 12 months afterwards. In the Begg group, the maxilla moved
      forward 1 mm more than in the Herbst group, and the mandible moved 1 mm more in
      the Herbst group than in the Begg group. The skeletal improvement in the Herbst
      group exceeded the changes in the Begg group by, on average, 2.0 mm (P <.01). The
      overjet reduction in the Begg group was larger (2.1 mm; P <.01) than in the
      Herbst group, mostly because of dental movements. The skeletal part of the
      overjet reduction was 4% in the Begg group compared with 51% in the Herbst group.
      The molar correction was similar in both groups, but in the Begg group, the
      skeletal improvement was 10%, compared with 66% in the Herbst group. The overbite
      correction and the increase in the anterior lower facial height and in the NSL/ML
      angle were larger in the Begg group (P <.05). The conclusions of this study were
      that the changes contributing to the Class II corrections in Begg and Herbst
      therapy were skeletal and dental. The skeletal changes were, however, larger in
      the Herbst-treated group. On the other hand, favorable and unfavorable vertical
      changes were more pronounced in the group treated with Class II elastics.

PMID- 10935955
TI  - Sagittal and vertical changes after treatment of Class II Division 1 malocclusion
      according to the Cetlin method.
AB  - This cephalometric study was designed to evaluate the dentoskeletal
      anteroposterior and vertical changes produced by Cetlin therapy (lower lip
      bumper, ACCO, cervical headgear) to correct Class II Division 1 malocclusion in
      the late mixed dentition. All measurements were made on 2 lateral headfilms, at
      pretreatment and at 1 year after beginning treatment. The selected sample (n =
      110; 67 boys and 43 girls; mean age, 10 to 11 years) and the control group (n =
      100; 48 boys, 52 girls; mean age, 10 to 11 years) matched for number, age, and
      malocclusion. The average observation interval was 13 months. The final
      measurements between intervals were averaged and tested for significance by
      analysis of variance. A one-factor (group) repeated measure model and a two
      factor (group and facial type) repeated measure model were fitted to each
      variable separately and significance values were set at P </=.05. The Class I
      molar relationship was achieved in all treated subjects primarily through
      distalization of upper first molars. A significant distal tipping was found in
      70% of the treated cases. The results showed a significant forward growth
      limitation of the maxilla with the use of cervical headgear. No significant
      change of mandibular position was found in the treated group compared with the
      control group. Both bite opening and proclination of upper and lower front teeth
      occurred. Cetlin therapy is reliable and effective for space recovery and
      interceptive Class II Division 1 treatment. Additional therapy may be needed
      later.

PMID- 10935956
TI  - Treatment timing for Twin-block therapy.
AB  - This cephalometric study evaluated skeletal and dentoalveolar changes induced by
      the Twin-block appliance in 2 groups of subjects with Class II malocclusion
      treated at different skeletal maturation stages in order to define the optimal
      timing for this type of therapy. Skeletal maturity in individual patients was
      assessed on the basis of the stages of cervical vertebrae maturation. The early
      treated group was composed of 21 subjects (11 females and 10 males). Mean age of
      these subjects at time 1 (immediately before treatment) was 9 years +/- 11
      months, and at time 2 (immediately after discontinuation of the Twin-block
      appliance) was 10 years 2 months +/- 11 months. According to the cervical
      vertebrae maturation staging at times 1 and 2, the peak in growth velocity was
      not included in the treatment period for any of the subjects in the early group.
      The late-treated group consisted of 15 subjects (6 females and 9 males). Mean age
      of this group was 12 years 11 months +/- 1 year 2 months at time 1 and 14 years 4
      months +/- 1 year 3 months at time 2. In the late group, treatment was performed
      during or slightly after the onset of the pubertal growth spurt. Both treated
      samples were compared with control samples consisting of subjects with untreated
      Class II malocclusions also selected on the basis of the stage in cervical
      vertebrae maturation. A modification of Pancherz's cephalometric analysis was
      applied to the lateral cephalograms of all examined groups at both time periods.
      Linear and angular measurements for mandibular dimensions, cranial base
      angulation, and vertical relationships were added to the original analysis.
      Annualized differences for all the variables from time 1 to time 2 were
      calculated for both treated groups and contrasted to the annualized differences
      in the corresponding untreated groups by means of nonparametric statistics. The
      findings of this short-term cephalometric study indicate that optimal timing for
      Twin-block therapy of Class II disharmony is during or slightly after the onset
      of the pubertal peak in growth velocity. When compared with treatment performed
      before the peak, late Twin-block treatment produces more favorable effects that
      include: (1) greater skeletal contribution to molar correction, (2) larger
      increments in total mandibular length and in ramus height, and (3) more posterior
      direction of condylar growth, leading to enhanced mandibular lengthening and to
      reduced forward displacement of the condyle in favor of effective skeletal
      changes. The importance of the biological evaluation of skeletal maturity in
      individual patients with Class II disharmony to be treated with functional
      appliances is emphasized.

PMID- 10935957
TI  - Center of resistance of anterior arch segment.
AB  - It is important to know the location of the center of resistance (CR) to control
      tooth movement. In this study, photoelastic techniques were used to determine the
      center of resistance. The photoelastic model included the anterior 4 maxillary
      teeth, which were interconnected firmly with 6 mm of space between lateral
      incisors and canines. Determination of the CR for the anterior arch segment was
      based on considerations of a wide variety of load conditions that generated the
      more uniform stresses in the supporting alveolar bone simulant. For the arch
      having the anterior 4 teeth connected, the CR was located within the mid-sagittal
      plane, 6-mm apical and 4-mm posterior to a line perpendicular to the occlusal
      plane from the labial alveolar crest of the central incisor.

PMID- 10935958
TI  - Effects of spring-loaded posterior bite-block appliance on masticatory muscles.
AB  - The effects of spring-loaded posterior bite-blocks on masticatory muscles were
      investigated to evaluate the correlation between masticatory muscles and
      craniofacial form in long-faced children. The appliance was used in 10 subjects
      (6 girls and 4 boys) with a chronological mean age of 10.40 +/- 1.12 years for
      the treatment of skeletal anterior open bite. Electromyographic activity of the
      anterior and posterior temporal and masseter muscles was recorded before and
      after treatment during postural position, maximal biting, chewing, swallowing,
      postural position with the appliance in the mouth, and maximal biting with the
      appliance in the mouth. After treatment, increases in SNB and overbite (P <.05, P
      <.001, respectively) and decreases in ANB, SNGoAr, and overjet parameters were
      found to be statistically significant (P <.05, P <.01). When the measurements
      related to muscle activity were examined, increases in anterior temporal postural
      (P <.05), anterior temporal chewing (P <.01), masseter chewing (P <.05),
      posterior temporal chewing (P <. 05), and masseter swallowing (P <.01) were found
      to be statistically significant. A positive correlation was found between ANB and
      anterior temporal postural and a negative correlation between SNGoAr and masseter
      swallowing. The increase in muscle activities was considered to occur as a result
      of the appliance used.

PMID- 10935959
TI  - The relationship of arch length to alterations in dental arch width.
AB  - An accurate method is presented for forecasting alterations in arch length
      related to various width increases in each dental arch. It is based on combined
      beta and hyperbolic cosine functions which express the expanded dental arches
      with correlation coefficients of r = 0.98, between measured data and
      representations of the dental arch. When the midpalatal suture is expanded,
      canine width and molar width alterations are not equal because the line of action
      of the expanding force is anterior to the center of resistance of the
      dentomaxillary complex. Therefore, canine to molar width ratio alterations of
      1:1, 1.25:1, and 1.5:1 are examined, and simple linear functions are presented
      for purposes of predicting changes in arch length.

PMID- 10935960
TI  - Study of craniofacial morphology and skeletal maturation in juvenile diabetics
      (Type I).
AB  - The aims of this study were to examine the craniofacial morphology of patients
      with juvenile diabetes, to investigate the effects of juvenile diabetes on
      general growth and skeletal maturation, and to analyze the pattern of association
      between craniofacial morphology and skeletal maturation in these patients. The
      sample consisted of 20 male patients with juvenile diabetes whose ages ranged
      from 14 to 16 years and who were affected with the condition at least 5 years
      before the study. Twenty normal subjects, with the same age range, were chosen as
      a control group. Height, weight, lateral cephalometric and hand-wrist radiographs
      were taken for all subjects, corrected for magnification distortion, and
      analyzed. The diabetic patients showed decreased skeletal maturation and
      decreased cephalometric linear and angular measurements when compared with the
      control group. These results should be considered when diabetic patients require
      orthodontic or orthopedic treatment.

PMID- 10935961
TI  - A role for TNF in bone resorption of deciduous molars in human beings.
AB  - In this study, tumor necrosis-alpha was sampled from the gingival crevice of
      human deciduous molars; this was compared with values measured from the crevice
      of those deciduous molars missing a permanent successor, and from the crevice of
      deciduous ankylosed molars. Tumor necrosis-alpha was harvested from the gingival
      crevice with magnetic microspheres coated with tumor necrosis-alpha antibodies.
      The amount of bead-bound tumor necrosis-alpha was quantified with the use of an
      enzyme-linked immunosorbent assay. One hundred seven sites (from 41 patients)
      were sampled; for each patient, the normal value was compared with either the
      molars missing a permanent successor or ankylosed value. The tumor necrosis-alpha
      levels were 1.6 times higher from the crevice of ankylosed deciduous molars when
      compared with normal deciduous molars and 2.6 times higher from the crevice of
      sites with a molar missing a permanent successor. The mean and standard error
      mean distribution of tumor necrosis-alpha expressed as picograms was: normal
      molars 91 pg (standard error mean +/- 20), ankylosed molars 150 pg (standard
      error mean +/- 31), and missing permanent successor 236 pg (standard error mean
      +/- 67). Analysis of variance showed the difference among the 3 means was close
      to attaining significant difference (F [2.104] = 2.7905, P =.066). Multiple
      comparison procedures indicated that the mean for molars missing a permanent
      successor and the normal groups were significantly different, P =.05. The results
      of this study suggest tumor necrosis-alpha values are elevated in the gingival
      crevice of deciduous molars with ankylosis and where the permanent tooth bud is
      congenitally missing.

PMID- 10935962
TI  - Nonsteroidal anti-inflammatory drugs in orthodontic tooth movement:
      metalloproteinase activity and collagen synthesis by endothelial cells.
AB  - Orthodontic treatment is based on the biologic principle that prolonged pressure
      on teeth results in remodeling of periodontal structures, allowing for tooth
      movement. Periodontal remodeling is a complex process regulated in part by
      prostaglandins and adversely affected by the use of nonsteroidal anti
      inflammatory drugs. We investigated the effects of indomethacin on collagenase
      activity and procollagen synthesis in rat endothelial cell cultures.
      Cyclooxygenase inhibition resulted in exacerbation of IL-1 beta-mediated
      collagenase B (MMP-9) production and activity, as well as attenuation of type IV
      procollagen synthesis levels by endothelial cells in vitro. Hence, the use of
      over-the-counter nonsteroidal anti-inflammatory drugs during tooth movement may
      result in aberrant remodeling of periodontal vasculature and other structures,
      ultimately affecting orthodontic treatment efficacy. Further studies are needed
      to establish novel pain relievers that do not interfere with orthodontic
      processes.

PMID- 10935963
TI  - Immunohistochemical localization of epidermal growth factor in cat paradental
      tissues during tooth movement.
AB  - Epidermal growth factor enhances proliferation and differentiation of cells
      during growth, maturation, and tissue healing. The objectives were to localize
      the epidermal growth factor in paradental cells and to determine the effect of
      orthodontic treatment on its concentrations in periodontal ligament fibroblasts,
      alveolar bone surface lining cells, and epithelial rests of Malassez. Sixty male
      cats, 1 year old, were divided into 2 groups: active and sham, and further
      divided into 10 time groups. In the active group, 1 maxillary canine was
      retracted by 80 g force; in the sham group, the animals received an inactive
      appliance. Sagittal sections of each half maxilla were stained for epidermal
      growth factor; staining intensity was measured microphotometrically in 10
      periodontal ligament fibroblasts, alveolar bone surface lining cells, and
      epithelial rests of Malassez cells in sites of periodontal ligament tension and
      compression, and in corresponding sites near control and sham canines. The
      overall mean staining intensity of the cells of the active group animals was
      30.47%, whereas that of the sham group was 21.78% (P <.0001). In all 3 types,
      cells near the actively treated canines stained significantly darker (P <.0001)
      than cells near the sham or control canines, particularly between 12 hours and 7
      days. These results demonstrate that orthodontic forces increase epidermal growth
      factor concentrations in paradental cells, suggesting that epidermal growth
      factor participates in the tissue remodeling that facilitates tooth movement.

PMID- 10935964
TI  - Adequacy of maxillary dental arch width in patients with palatally displaced
      canines.
AB  - This study investigates maxillary dental arch width in subjects with palatally
      displaced canines. Pretreatment dental casts of orthodontic patients with one or
      both maxillary canines palatally displaced (n = 31; male, 10; female, 21) were
      collected. This sample was matched according to sex and age with pretreatment
      dental casts from unaffected orthodontic patients. Arch widths were recorded
      between the maxillary first premolars and between the maxillary first molars.
      Interpremolar arch width and intermolar arch width comparisons between the sample
      with palatally displaced canines and the reference sample showed no statistically
      significant differences in their means, thus indicating that there was no
      statistically significant difference in the anterior and posterior arch width
      between the affected subjects and the control subjects. Thus, affected patients
      exhibit adequacy of maxillary dental arch width. This evidence refutes earlier
      conclusions that deficiency in maxillary transverse arch width is an associated
      contributing factor in the genesis of the anomaly of palatally displaced canines.
      Clinically, adequacy of dental arch width helps explain the "nonextraction"
      diagnostic appearance of most of these patients when they present for treatment.

PMID- 10935965
TI  - Esthetic management of an unerupted maxillary central incisor with a closed
      eruption technique.
AB  - In cases of orthodontic traction of unerupted teeth, gingival recession and long
      clinical crowns are often seen. Satisfactory esthetic demands are not always met.
      A case of an unerupted maxillary central incisor is presented, in which traction
      was used, with emphasis on the surgical technique and the direction of the pull.
      The result was clinically favorable. The appearance of gingival margin was
      restored.

PMID- 10935967
TI  - Earn 3 hours of CE credit

PMID- 10935966
TI  - Treatment of a Class II Division 1 malocclusion.
AB  - This case was presented as part of the American Board of Orthodontics case
      displays at the 1999 AAO meeting. It was selected to be submitted for the
      publication in the American Journal of Orthodontics and Dentofacial Orthopedics
      by the ABO.

PMID- 10935968
TI  - Advanced PowerPoint animation techniques: part II.

PMID- 10935969
TI  - Litigation, legislation, and ethics. Dental records as evidence.

PMID- 10935970
TI  - Characterization of substance P-membrane interaction by transferred nuclear
      Overhauser effect.
AB  - Substance P, one of the mammalian tachykinins, is known to interact strongly with
      lipid bilayers and this interaction may play a role in the receptor-peptide
      recognition process. The conformation of substance P bound to vesicles consisting
      of perdeuterated phosphatidylcholine has been investigated by means of two
      dimensional transferred nuclear Overhauser (trNOE) spectroscopy. Nuclear magnetic
      resonance data analysis resulted in a unique conformational family characterized
      by a well-defined conformation of the last seven C-terminal amino acids, which
      consists of a sequence of nonstandard turns following each other in a helix-like
      manner. The absence of short- or medium-range trNOE in the N-terminal part
      indicates its structural flexibility.

PMID- 10935971
TI  - Computation of writhe in modeling of supercoiled DNA.
AB  - We describe four previously unpublished methods allowing the computation of the
      writhe for a supercoiled DNA molecule modeled by a polymer chain consisting of
      straight segments. These methods are compared with each other in terms of
      computational efficiency and the scope of their applicability is discussed.

PMID- 10935973
TI  - Determination of the sedimentation coefficient distribution by least-squares
      boundary modeling.
AB  - A new method is presented for the calculation of apparent sedimentation
      coefficient distributions g*(s) for the size-distribution analysis of polymers in
      sedimentation velocity experiments. Direct linear least-squares boundary modeling
      by a superposition of sedimentation profiles of ideal nondiffusing particles is
      employed. It can be combined with algebraic noise decomposition techniques for
      the application to interference optical ultracentrifuge data at low loading
      concentrations with significant systematic noise components. Because of the use
      of direct boundary modeling, residuals are available for assessment of the
      quality of the fits and the consistency of the g*(s) distribution with the
      experimental data. The method can be combined with regularization techniques
      based on F statistics, such as used in the program CONTIN, or alternatively, the
      increment of s values can be adjusted empirically. The method is simple, has
      advantageous statistical properties, and reveals precise sedimentation
      coefficients. The new least-squares ls-g*(s) exhibits a very high robustness and
      resolution if data acquired over a large time interval are analyzed. This can
      result in a high resolution for large particles, and for samples with a high
      degree of heterogeneity. Because the method does not require a high frequency of
      scans, it can also be easily used in experiments with the absorbance optical
      scanning system. Published 2000 John Wiley & Sons, Inc.

PMID- 10935972
TI  - Changes at the floor of the peptide-binding groove induce a strong preference for
      proline at position 3 of the bound peptide: molecular dynamics simulations of HLA
      A*0217.
AB  - We report on molecular dynamics simulations of major histocompatibility complex
      (MHC)-peptide complexes. Class I MHC molecules play an important role in cellular
      immunity by presenting antigenic peptides to cytotoxic T cells. Pockets in the
      peptide-binding groove of MHC molecules accommodate anchor side chains of the
      bound peptide. Amino acid substitutions in MHC affect differences in the peptide
      anchor motifs. HLA-A*0217, human MHC class I molecule, differs from HLA-A*0201
      only by three amino acid residues substitutions (positions 95, 97, and 99) at the
      floor of the peptide-binding groove. A*0217 showed a strong preference for Pro at
      position 3 (p3) and accepted Phe at p9 of its peptide ligands, but these
      preferences have not been found in other HLA-A2 ligands. To reveal the structural
      mechanism of these observations, the A*0217-peptide complexes were simulated by
      1000 ps molecular dynamics at 300 K with explicit solvent molecules and compared
      with those of the A*0201-peptide complexes. We examined the distances between the
      anchor side chain of the bound peptide and the pocket, and the rms fluctuations
      of the bound peptides and the HLA molecules. On the basis of the results from our
      simulations, we propose that Pro at p3 serves as an optimum residue to lock the
      dominant anchor residue (p9) tightly into pocket F and to hold the peptide in the
      binding groove, rather than a secondary anchor residue fitting optimally the
      complementary pocket. We also found that Phe at p9 is used to occupy the space
      created by replacements of three amino acid residues at the floor within the
      groove. These findings would provide a novel understanding in the peptide-binding
      motifs of class I MHC molecules.

PMID- 10935974
TI  - A priori crystal structure prediction of native celluloses.
AB  - The packing of beta-1,4-glucopyranose chains has been modeled to further
      elaborate the molecular structures of native cellulose microfibrils. A chain
      pairing procedure was implemented that evaluates the optimal interchain distance
      and energy for all possible settings of the two chains. Starting with a rigid
      model of an isolated chain, its interaction with a second chain was studied at
      various helix-axis translations and mutual rotational orientations while keeping
      the chains at van der Waals separation. For each setting, the sum of the van der
      Waals and hydrogen-bonding energy was calculated. No energy minimization was
      performed during the initial screening, but the energy and interchain distances
      were mapped to a three-dimensional grid, with evaluation of parallel settings of
      the cellulose chains. The emergence of several energy minima suggests that
      parallel chains of cellulose can be paired in a variety of stable orientations. A
      further analysis considered all possible parallel arrangements occurring between
      a cellulose chain pair and a further cellulose chain. Among all the low-energy
      three-chain models, only a few of them yield closely packed three-dimensional
      arrangements. From these, unit-cell dimensions as well as lattice symmetry were
      derived; interestingly two of them correspond closely to the observed allomorphs
      of crystalline native cellulose. The most favorable structural models were then
      optimized using a minicrystal procedure in conjunction with the MM3 force field.
      The two best crystal lattice predictions were for a triclinic (P(1)) and a
      monoclinic (P2(1)) arrangement with unit cell dimensions a = 0.63, b = 0.69, c =
      1.036 nm, alpha = 113.0, beta = 121.1, gamma = 76.0 degrees, and a = 0.87, b =
      0.75, c = 1.036 nm, gamma = 94.1 degrees, respectively. They correspond closely
      to the respective lattice symmetry and unit-cell dimensions that have been
      reported for cellulose Ialpha and cellulose Ibeta allomorphs. The suitability of
      the modeling protocol is endorsed by the agreement between the predicted and
      experimental unit-cell dimensions. The results provide pertinent information
      toward the construction of macromolecular models of microfibrils.

PMID- 10935975
TI  - Kinetics of beta-casein hydrolysis by wild-type and engineered trypsin.
AB  - Apparent rate constants of tryptic hydrolysis of amide bonds containing Arg and
      Lys residues in beta-casein were determined by the analysis of kinetics of
      accumulation of 17 major peptide components revealed by high performance liquid
      chromatography. When studying pH influence on Arg/Lys bond cleavage preference,
      averaged rate constants over several Arg&bond;X and Lys&bond;X bonds were used
      for analysis of kinetics of wild-type trypsin, K188H, K188F, K188Y, K188W, and of
      K188D/D189K mutants. The pK(a1) value of 6.5 was found for all studied trypsins.
      For wild-type trypsin and its K188D/D189K mutant, pK(a2) was found to be 10. The
      lowest among studied engineered trypsins pK(a2) = 9.3 was determined for K188Y
      mutant. Considerable preference for the cleavage of Arg over Lys containing
      peptide bonds was demonstrated for all trypsins with engineered S2 site except
      for K188H and K188F. The comparison of individual rate constants for various
      bonds showed that during the hydrolysis by wild-type trypsin, the probabilities
      of splitting depend on secondary specificity and local hydrophobicity of amino
      acid residues, which are nearest to the hydrolyzed peptide bond (P2 site). The
      improvement of prediction of hydrolysis rates performed by the used program was
      achieved after considering the presence of hydrophobic neighborhood of Lys48-
      Ile49 and Arg202--Gly203 bonds.

PMID- 10935976
TI  - Structure of a cyclic dimer of amino undecanoic acid as a model of folding and
      hydration in polyamides, polypeptides, and related substances.
AB  - Aliphatic amides are often used in the synthesis of peptidomimetic compounds.
      Here we present the structure of two cyclic dimers of aminoundecanoic acid as
      determined by x-ray diffraction. Each dimer contains two peptide groups and
      twenty methylene units. In one of the crystal structures, water is associated
      with the peptide groups, forming a chain of hexagons similar to those found in
      crambin, and in other protein and nucleic acid crystals. The aminoundecanoic
      rings show a fold at the peptide group, similar to either beta-turn type III or V
      found in proteins. Such folds are an adequate model for the peptide bond
      structure in nylon crystallites and peptidomimetic compounds.

PMID- 10935977
TI  - Further evidence for an association between maternal smoking and
      craniosynostosis.

PMID- 10935978
TI  - Frog limb deformities: an "eco-devo" riddle wrapped in multiple hypotheses
      surrounded by insufficient data.

PMID- 10935980
TI  - Teratology society public affairs committee position paper: thalidomide.

PMID- 10935979
TI  - Hind limb malformations in free-living northern leopard frogs (Rana pipiens) from
      Maine, Minnesota, and Vermont suggest multiple etiologies.
AB  - BACKGROUND: Reports of malformed frogs have increased throughout the North
      American continent in recent years. Most of the observed malformations have
      involved the hind limbs. The goal of this study was to accurately characterize
      the hind limb malformations in wild frogs as an important step toward
      understanding the possible etiologies. METHODS: During 1997 and 1998, 182
      recently metamorphosed northern leopard frogs (Rana pipiens) were collected from
      Minnesota, Vermont, and Maine. Malformed hind limbs were present in 157 (86%) of
      these frogs, which underwent necropsy and radiographic evaluation at the National
      Wildlife Health Center. These malformations are described in detail and
      classified into four major categories: (1) no limb (amelia); (2) multiple limbs
      or limb elements (polymelia, polydactyly, polyphalangy); (3) reduced limb
      segments or elements (phocomelia, ectromelia, ectrodactyly, and brachydactyly;
      and (4) distally complete but malformed limb (bone rotations, bridging, skin
      webbing, and micromelia). RESULTS: Amelia and reduced segments and/or elements
      were the most common finding. Frogs with bilateral hind limb malformations were
      not common, and in only eight of these 22 frogs were the malformations
      symmetrical. Malformations of a given type tended to occur in frogs collected
      from the same site, but the types of malformations varied widely among all three
      states, and between study sites within Minnesota. CONCLUSIONS: Clustering of
      malformation type suggests that developmental events may produce a variety of
      phenotypes depending on the timing, sequence, and severity of the environmental
      insult. Hind limb malformations in free-living frogs transcend current
      mechanistic explanations of tetrapod limb development.

PMID- 10935981
TI  - AIDS in an HIV-seronegative Ghanaian woman with intersubtype A/G recombinant HIV
      1 infection.
AB  - A 29-year-old Ghanaian woman who developed AIDS while being HIV-antibody
      seronegative was investigated during a collaborative study aimed at the
      identification of viral causes of a HIV-seronegative AIDS syndrome in West
      Africa. Plasma was screened with a panel of EIA tests for antibodies to HIV and
      HIV-1 p24 antigen. Retroviral infection was investigated by detection of reverse
      transcriptase (RT) activity in plasma, viral RNA amplification and
      quantification, and virus isolation. Positive amplification products were
      sequenced and phylogenetic analyses were carried out. Most EIA tests were unable
      to demonstrate the presence of anti-HIV anti-bodies, whereas confirmatory assays
      yielded inconclusive results. Retroviral infection was documented by detection of
      RT activity, HIV-1-specific genomic amplification and virus isolation. This virus
      was HIV-1 subtype A with an unusual six amino acid insertion in the gp120 V4 loop
      and with the nef gene of subtype G. The patient's plasma did not react with
      either autologous or heterologous viral lysates or HIV-1 peptides, whereas
      antibodies to other viral antigens were present. In conclusion, the Ghanaian
      patient exhibited a rare subtype A/G recombinant HIV-1 infection with a near
      absence of a HIV-specific humoral response. The lack of detectable antibody
      response might be due to either a highly pathogenic, rapidly fatal, HIV-1
      infection preventing the development of the typical humoral immune response or to
      a host-related dysfunction of the immune system. Direct antigenemia or genomic
      detection of the virus should be undertaken when clinical or biological data
      suggests an HIV infection in the absence of serological evidence.

PMID- 10935982
TI  - Higher HIV-1 RNA cutoff level required in cerebrospinal fluid than in blood to
      predict positive HIV-1 isolation.
AB  - HIV-1 can be isolated from the vast majority of blood samples taken from HIV-1
      seropositive patients not treated with antiretroviral drugs. Isolation rates from
      cerebrospinal fluid (CSF) samples are considerably lower, ranging between 20-70%.
      The objective of this study was to determine the cutoff levels for HIV-1 RNA that
      would yield a positive predictive value > or =90% for positive virus isolation
      from CSF and blood. Quantitative HIV-1 RNA PCR (Amplicor HIV monitor, version
      1.0, Roche Diagnostic Systems) and virus isolation were used to examine 303 CSF
      samples and 278 paired blood samples from 157 HIV-1-seropositive patients.
      Patients on antiretroviral treatment provided 140 of the CSF samples and 131 of
      the blood samples. CSF samples that were positive by culture numbered 137 of 303
      (45%), as compared with 216 of 278 (78%) blood samples. In the case of samples
      taken from patients with antiretroviral treatment, 28% were positive by culture
      from CSF and 63% from blood. As expected, mean HIV-1 RNA levels were higher in
      CSF and blood samples positive by culture than in samples negative by culture. A
      cutoff level of >5,000 HIV-1 RNA copies/ml was required to yield a positive
      predictive value for positive virus isolation from CSF samples of > or =90%,
      whereas the cutoff level for blood samples was just above the detection limit of
      the assay (>200 HIV-1 copies/ml).

PMID- 10935983
TI  - Identification and characterization of sera from HIV-infected individuals with
      broad cross-neutralizing activity against group M (env clade A-H) and group O
      primary HIV-1 isolates.
AB  - A previous study on cross-clade neutralization activity, identified three key
      isolates, MNlab (envB/gagB; X4 coreceptor), VI525 (envG/gagH, envA/gagA; R5X4)
      and CA9 (Group O; R5), that allowed discrimination of sera, likely or unlikely to
      neutralize primary HIV-1 isolates belonging to Group M (env clades A-H) and Group
      O. The prognostic ability of these three isolates was verified by means of an
      external validation on a different and larger set of sera. A total of 79
      different sera (66 HIV-1, 10 HIV-2, 1 HIV-1+2 and 2 SIV(cpz)) were examined first
      for their capacity to neutralize the three key isolates, next sera were
      challenged against 12 other primary HIV-1 isolates of Group M (env A-H) and 2
      isolates of Group O. Sera that neutralized all three isolates with an ID(50)
      titer of > or =1/40, also neutralized the 14 other primary isolates belonging to
      different genetic groups and clades. Sera that did not neutralize all three
      isolates did not exert broad cross-neutralizing activity. The neutralizing
      activity was antibody-mediated because it was absorbed and eluted from a Prot-G
      column. Competition-neutralization experiments using recombinant gp120 (HIV-1
      MNlab) reduced the neutralizing capacity, suggesting that the neutralizing
      antibodies were directed against the Env protein. Remarkably, the broad cross
      neutralization activity was found primarily in African female patients. In
      conclusion, this study confirms that three isolates are sufficient to allow
      identification of broad cross-neutralizing sera.

PMID- 10935984
TI  - Laboratory signs of acute or recent cytomegalovirus infection are common in
      cirrhosis of the liver.
AB  - Human cytomegalovirus (CMV) is an ubiquitous pathogen that can cause severe and
      often fatal infections in immunocompromised patients. Patients with cirrhosis
      often show various degrees of impaired cellular immunity that could lead to acute
      CMV reactivation. The aim of the present study was to determine whether
      laboratory findings of active CMV infections are common in patients with
      cirrhosis. Fifty-five patients with cirrhosis were studied for acute CMV
      infection by virological (antigenemia and quantitative polymerase chain reaction
      in polymorphonuclear leukocytes) and serological (detection of anti-CMV IgM by
      immunoblot) methods. The same tests were carried out on 50 blood donors and on 20
      chronic hepatitis patients, considered as control populations. Acute or recent
      CMV infection had occurred in 31 (56%) of 55 patients with cirrhosis, whereas
      only 1 out of 20 (5%) patients with chronic non-cirrhotic liver disease and none
      of the 50 blood donors had laboratory signs of active CMV infection. The
      difference between patients with cirrhosis and the control groups was significant
      (P < 0.001, chi(2) test). CMV in patients with cirrhosis was not related to age,
      gender, hepatitis C virus infection or hepatocellular carcinoma. There was no
      significant correlation between impairment of liver function and the presence of
      active CMV infection. Patients with cirrhosis should be considered at risk for
      CMV infection, that seems to be mild and asymptomatic.

PMID- 10935985
TI  - Immune response to the herpes simplex type 1 regulatory proteins ICP8 and VP16 in
      infected persons.
AB  - The specific immune responses directed against the viral single stranded (ss) DNA
      binding protein ICP8 and the transactivator of immediate early (IE) gene
      expression VP16 (alpha-trans inducing factor, Vmw65) in HSV type 1 seropositive
      humans were examined. The results described in this paper indicate that neither
      ICP8 nor VP16 were able to induce a recall response in lymphocytes of healthy HSV
      seropositive individuals without recurrent infection, although CD4+ T cells
      purified from these individuals responded to both viral proteins in vitro when
      monocyte derived dendritic cells were used as antigen presenting cells. A recall
      response, however, could be induced to both viral proteins in T cells of patients
      with recurrent HSV infections when blood monocytes were used. Moreover, ICP8- and
      VP16-specific antibodies could be detected in the serum of patients with
      recurrent HSV infections whereas, in contrast, these antibodies were virtually
      absent in healthy HSV seropositive individuals without recurrences. These data
      represent the first systematic study of the immunological properties of ICP8 in
      humans, indicating a significant difference in the response to the essential
      viral regulators ICP8 and VP16 in HSV-1 seropositive healthy individuals as
      opposed to patients with recurrent HSV-1 infections.

PMID- 10935986
TI  - Rapid strip assay for detection of anti-herpes simplex virus antibodies:
      application to prediction of varicella-zoster virus reactivation in patients with
      acute peripheral facial palsy.
AB  - Varicella-zoster virus (VZV) reactivation causes acute peripheral facial palsy in
      the majority (88%) of patients who lack anti-herpes simplex virus (HSV)
      antibodies, suggesting that an absence of anti-HSV antibodies is a reliable
      serological marker for the diagnosis of VZV reactivation in patients who are
      diagnosed initially as idiopathic peripheral facial palsy (Bell's palsy) [Furuta
      et al., 2000] Clinical Infectious Diseases]. A simple and rapid immunoassay for
      detection of anti-HSV antibodies based on HSV type 1 glycoprotein D was developed
      by modifying the conventional Western blot technique. The assay was evaluated by
      comparing the results with those of conventional Western blot. In total, 100 sera
      obtained from patients with acute peripheral facial palsy were tested and judged
      blindly by two investigators. Twenty-four of 26 HSV-seronegative sera were
      obtained from patients with VZV reactivation (Ramsay Hunt syndrome or zoster sine
      herpete). The sensitivity of the assay was over 95% and the specificity was 100%.
      The two investigators agreed on the diagnosis in 99 of the 100 sera. These
      results indicate that the rapid strip assay is applicable to prediction of VZV
      reactivation in patients diagnosed clinically with Bell's palsy before zoster
      lesions appear or PCR using saliva samples indicates VZV reactivation.

PMID- 10935987
TI  - Reactivation of varicella-zoster virus in delayed facial palsy after dental
      treatment and oro-facial surgery.
AB  - In rare cases, acute peripheral facial palsy occurs several days after dental
      treatment and oro-facial surgery. Surgical procedures have been known to trigger
      reactivation of varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV
      1). The present study examined eight patients who exhibited delayed facial palsy
      after dental treatment or oro-facial surgery. Ramsay Hunt syndrome was diagnosed
      in three patients and varicella-zoster virus (VZV) reactivation without zoster
      lesions (zoster sine herpete) was diagnosed in three patients either by PCR or
      serological assay. Therefore, VZV reactivation was detected in 75% (6 of 8) of
      patients who exhibited delayed facial palsy after dental or oro-facial treatment.
      The results suggest that VZV reactivation is a major cause of delayed facial
      palsy after dental treatment or oro-facial surgery.

PMID- 10935988
TI  - Low induction of varicella-zoster virus-specific secretory IgA antibody after
      vaccination.
AB  - Breakthrough after varicella vaccination occurs in approximately 2. 6%
      approximately 18.6% of immunocompetent children, but the reason has not been
      demonstrated clearly. As a first defense, specific secretory IgA antibody on the
      mucosa plays an important role in preventing invasion of microorganisms. To
      examine induction of varicella-zoster virus (VZV) specific secretory IgA after
      natural infection and vaccination and its booster mechanisms, 143 salivary
      samples were tested by ELISA. The VZV-secretory IgA values were significantly
      higher in the matched children after natural chickenpox than in those after
      vaccination, although the total secretory IgA did not differ between them. Two
      (7%) of the vaccinees lacked the sIgA antibody. In the elderly and in
      immunocompromised children, the VZV-secretory IgA values were no lower than those
      in healthy children, and they did not lack VZV-secretory IgA. The doctors and
      nurses taking care of patients with chickenpox had higher values than the other
      groups as did individuals who had had herpes zoster recently. VZV-secretory IgA
      was thought to be stimulated by exogenous and reactivated endogenous VZV to
      neutralize VZV with weak activity. These results suggest that low or no induction
      of VZV-secretory IgA antibody after vaccination may be one of the possible
      explanations for a breakthrough.

PMID- 10935989
TI  - Human herpesvirus 6 infection after living related liver transplantation.
AB  - The aim of the study was to investigate human herpesvirus-6 (HHV-6) infection
      after liver transplantation from living related donors, and to evaluate the
      reliability of the presence of HHV-6 DNA in plasma by the polymerase chain
      reaction (PCR) for monitoring active HHV-6 infection. EDTA peripheral blood was
      collected from 47 donor and recipient (16 males and 31 females, age 1-320 months)
      pairs at the time of transplantation and biweekly from these recipients after
      transplantation until 2 months after operation. Isolation of HHV-6 and
      serological assays were carried out to evaluate active HHV-6 infection in this
      study. The presence of the viral DNA in plasma was tested by nested PCR. Four
      clinical events, such as unexplained fever, thrombocytopenia, rejection, and
      central nervous system (CNS) involvement, were evaluated for clinical features of
      the virus infection. Risk factors for the virus activity after liver
      transplantation were also examined. HHV-6 activity was detected in 23 (49%) of
      the 47 recipients approximately 2-4 weeks after transplantation. All 9 isolates
      were HHV-6 variant B. The presence of the viral DNA in plasma correlated well
      with virus isolation and serology (P < 0.01). Only unexplained fever was
      associated statistically with HHV-6 activity after liver transplantation (P < 0.
      01). If the recipient was seronegative to HHV-6 before transplantation, the
      recipient was more likely to develop the active virus infection after liver
      transplantation (P = 0.11). HHV-6 activity occurred in one-half of the recipients
      approximately 2-4 weeks after liver transplantation, and there was a close
      association between HHV-6 activity and unexplained fever following
      transplantation. Detection of the viral DNA in plasma by PCR is useful for
      monitoring active HHV-6 infection in these patients. Seronegative recipients were
      more likely to have evidence of active HHV-6 infection after liver
      transplantation.

PMID- 10935991
TI  - Group B coxsackievirus myocarditis and pancreatitis: connection between viral
      virulence phenotypes in mice.
AB  - The group B coxsackieviruses (CVB) induce experimental pancreatitis and
      myocarditis in mice and are established agents of human myocarditis, especially
      in children. We tested the hypothesis that the development of CVB-induced
      myocarditis is linked to CVB-induced pancreatitis by studying the replication of
      different CVB strains in mice. Eight of nine genotypically different type 3 CVB
      (CVB3) strains induced acute pancreatitis in mice; of these, three viruses also
      induced acute myocarditis. One CVB3 strain was avirulent for both organs.
      Myocarditis was not observed in the absence of pancreatitis. The results obtained
      by inoculation of mice with strains of other CVB serotypes were consistent with
      these data. Infectious virus titers were measured in serum, pancreas, and heart
      as a function of time after inoculation of mice with three CVB3 strains. Each
      strain was representative of one of the three viral virulence phenotypes:
      avirulent, pancreovirulent only, and cardiovirulent. All strains replicated well
      and persisted in the pancreas through 8 days post-inoculation, but the
      cardiovirulent CVB3 strain tended to replicate to higher titer earlier and
      persist longer in sera, pancreatic, and cardiac tissues than the
      noncardiovirulent strains. Replication of the CVB3 strains were studied in two
      human pancreatic tumor lines and in primary human endothelial cell cultures
      derived from cardiac artery. Cardiovirulent strains, both individually and as a
      group, tended to replicate to titers as high as, or higher than,
      noncardiovirulent strains did in cell culture. The data are consistent with the
      possibility of an etiologic link between CVB-induced pancreatic and heart
      disease.

PMID- 10935992
TI  - GBV-C/HGV genotypes: proposed nomenclature for genotypes 1-5.
AB  - The GB virus-C and hepatitis G virus (GBV-C/HGV) are variants of the same
      flavivirus. This proposal attempts to clarify the conflicting nomenclature for
      GBV-C/HGV genotypes. The first three genotypes described were genotype 1 (West
      Africa); genotype 2 (US/Europe) and genotype 3 (Asia). Subsequently, two groups
      published data from South Africa and Southeast Asia both stating the presence of
      a novel "4th genotype." These isolates are distinct phylogenetically. It is
      proposed that the nomenclature for genotypes 1-3 remains as per previous
      publications, and that the Southeast Asian isolates be known as genotype 4, and
      the South African isolates as genotype 5.

PMID- 10935990
TI  - Four putative subtypes of human parvovirus B19 based on amino acid polymorphism
      in the C-terminal region of non-structural protein.
AB  - The nucleotide sequence of 10 isolates of human parvovirus B19 (B19) were
      determined and compared throughout 96.3% of the open reading frames (4145
      nucleotides from nt. 509-4653). In the 4145 nucleotides, 122 mutation sites were
      found, of which 24 were accompanied by amino acid displacement. Furthermore, the
      polymorphism of the amino acids was seen in about 110 bases near the carboxy
      terminal of the non-structural protein, ranging from nt. 2011 to 2123, where four
      amino acid mutation points were found to exist. Based on the amino acid
      polymorphism of these four mutation sites in this area, 10 isolates of the B19
      parvovirus could be divided into 4 subtypes (subtypes A, B, C, and D). The
      frequency of isolation of the subtypes depended on the time and location of
      collection of the B19 viremic blood specimens.

PMID- 10935993
TI  - Molecular characterisation of HCV genotype 4 isolates circulating in Italy.
AB  - The characteristics of genotype 4 subtype variability of HCV isolates circulating
      in Italy were studied. The viral isolates were identified from 736 HCV-RNA
      positive sera originated from seroepidemiological studies undertaken in 4
      different regions of North, South Italy and Sardinia. 24 out of 28 genotype 4
      isolates (86%) were classified by phylogenetic analysis of E1 genome region (915
      1128) as belonging to subtype 4d (Neighbour Joining Method). Three isolates
      classified as subtype 4a were detected in haemophilic patients, possibly related
      to infections from blood products. One isolate classified as a new subtype
      derived from an Eritrean patient subjected to haemodialysis. Very high genome
      homogeneity (mean 4.3%) was shown by genetic comparisons (DNA dist programs
      Phylip Package) for all the 4d isolates relative to the studies performed in
      Veneto, Calabria and Sardinia and originated from subjects from the general
      population and outpatients (19 subtype 4d isolates out of 24). In the 3 studies
      different prevalence rates of HCV genotype 4 (3.1%, 1. 3%, 14% respectively) were
      found. In contrast a considerable degree of heterogeneity, both intragroup and
      with the other groups (mean 8. 2% and 8.7%, respectively) was observed among
      subtype 4d isolates identified in the patients of a haemodialysis centre in
      Apulia region. In conclusion the subtype 4d of genotype 4 was highly prevalent
      and endemic in Italy. An elevated level of viral heterogeneity was observed in
      one study carried out in a region of Southern Italy. This can be related to a
      longer period of past endemicity of this genotype and to a high level of exposure
      to reinfections in particular categories of patients such as haemodialysis
      patients.

PMID- 10935994
TI  - Resistance of recent measles virus wild-type isolates to antibody-mediated
      neutralization by vaccinees with antibody.
AB  - The neutralization capacity of sera from Luxembourgian adolescent vaccinees and
      from Nigerian women with measles-induced immunity to a number of measles virus
      strains was compared. Although both cohorts were matched for their
      hemagglutination inhibition and standard neutralization titers, 12 of the 22 late
      convalescent sera, and only 6 of 24 vaccinees neutralized all viruses. Similarly,
      only 2 of 20 viruses were not neutralized by at least 75% of late convalescent
      sera, in comparison to 10 of 20 viruses that resisted neutralization by at least
      75% of the vaccinees. The more resistant viruses were not limited to a certain
      clade. One Nigerian virus was resistant to neutralization by 30% of the late
      convalescent women and by 75% of vaccinees. These results suggest that
      qualitative differences in neutralizing antibodies may reduce further protection
      of infants by passively acquired immunity against wild-type viruses when
      vaccinated girls become mothers.

PMID- 10935995
TI  - Distinct epidemiological patterns of Norwalk-like virus infection.
AB  - Norwalk-like viruses (NLV) are important economically as a cause of both sporadic
      gastroenteritis in the community and large outbreaks in hospitals and other
      institutional settings. Despite the description of several antigenic types
      relatively little is known about the epidemiology of these individual types. NLVs
      were detected by electron microscopy in faecal specimens from 706 outbreaks of
      gastroenteritis that represented 68% of all outbreaks of non-bacterial
      gastroenteritis. These outbreaks took place in the counties of West and North
      Yorkshire and Humberside during six winter seasons between July 1992 and June
      1998. NLV strains from 671 outbreaks were typed by antigen capture enzyme linked
      immunosorbent assays (ELISA) based on antisera made to recombinant virus-like
      particles of three antigenically distinct NLVs; Norwalk (NV), Mexico (MXV) and
      Grimsby (GRV) viruses. GRV was the predominant strain for five of the six winter
      seasons and overall was associated with 61% of NLV outbreaks. MXV was responsible
      for a single epidemic peak in the winter of 1993/94 but was also observed at
      other times throughout the study period. NV was only associated with two
      outbreaks in 1994 that were epidemiologically linked. Strains from the remaining
      32% of outbreaks were non-reactive in all three ELISA. Thus, a single NLV
      antigenic type seems to have predominated during the period 1992 to 1998 in the
      UK.

PMID- 10935996
TI  - Detection of TT virus sequences in children with liver disease of unknown
      etiology.
AB  - DNA sequences of TT virus (TTV) in 55 serum samples taken from 20 children with
      liver disease of unknown etiology (16 with acute liver disease, 2 with fulminant
      hepatitis, and 2 with chronic liver disease) and from 35 healthy children as
      controls were examined by using the hemi-nested polymerase chain reaction (PCR).
      The PCR was carried out using the established primers (NG059, NG061, NG063) to
      amplify TTV DNA sequences. The sequences were detected in 6 of the 20 patients
      (30.0%) with liver disease and in 5 of the 35 healthy children (14.2%) by direct
      gel analysis. There was no significant difference between the prevalence of liver
      disease patients and controls. However, both patients with fulminant hepatitis
      and both patients with chronic hepatitis had TTV DNA sequences. Four of the six
      TTV isolates from liver disease patients were genotype 1a, whereas only one of
      the five TTV isolates from controls was genotype 1a. Although the study
      population was small, it is possible that genotype 1a of TTV might be more
      pathogenic than other genotypes in children.

PMID- 10935997
TI  - Prevalence and phylogenetic characterisation of TT-virus in the blood donor
      population of Auckland, New Zealand.
AB  - TT-virus (TTV, patient initials: T.T.), a novel DNA virus, was first isolated in
      Japan in 1997 from serum of a patient with post-transfusion hepatitis of unknown
      aetiology. To date, the contribution of TTV to liver disease remains doubtful.
      The potential for transmission via blood and blood products makes it essential to
      establish the prevalence of TTV viraemia in the blood donor population. 413 blood
      donor serum samples were chosen randomly, the DNA was extracted and TTV-specific
      DNA amplified by nested polymerase chain reaction (PCR). TTV infection was
      present in 13 out of 413 (3.15%) blood donors in the Auckland region of New
      Zealand using a set of primers targeting open reading frame (ORF) 1. These 13
      amplification products (264 bp) were sequenced and TTV genotypes determined.
      Alignment with published TTV sequences showed that seven (53.8%) of the thirteen
      positive serum samples belonged to genotype 1, five (38.5%) belonged to genotype
      2 and one (7.7%) could not be classified as either genotype 1 or 2. One hundred
      twenty-seven blood donor serum samples were retested with a second set of primers
      targeting the 5' region of the TTV genome in a single round PCR. Forty-three
      samples were positive for TTV DNA with these primers resulting in a prevalence of
      37%. The data demonstrate that TTV is present among New Zealand blood donors and
      support the need for further investigation into the natural history of TTV
      infection.

PMID- 10935999
TI  - Benefits of new catheter mapping technology: fact or fiction?

PMID- 10936000
TI  - Pharmacological atrial defibrillation via temporarily occluded coronary sinus:
      first clinical experience and implications for an implantable device.
AB  - The aim of this paper is to report the first experience of pharmacological atrial
      defibrillation in humans via a temporarily occluded coronary sinus. PATIENTS AND
      METHODS: In 6 patients (3 women, 3 men; mean age 57.8y, min 31, max 71), with
      clinical recurrences of atrial fibrillation, an occlusive coronary venogram was
      carried out in order to establish the origin of the Vein of Marshall. Atrial
      fibrillation was then induced by atrial pacing in all the patients and after an
      adequate waiting period to assure that the atrial fibrillation episode was
      persistent and stable, a bolus of a very low dose of an antiarrhythmic drug was
      delivered in 3-4 seconds into the temporarily balloon occluded coronary sinus
      near the orifice of the vein of Marshall. For both the venogram and the
      pharmacological test a Baim-Turi (USCI-Bard, Billerica MA) or a Vueport (Cardima,
      Fremont CA) catheter was used. RESULTS AND COMMENTS: In five patients a single
      dose of 7 mg of propafenone was immediately effective in restoring the sinus
      rhythm. In the remaining patient 2 doses of 7mg of propafenone failed to
      interrupt the arrhythmia, which was subsequently interrupted by a bolus of 0.1mg
      of ibutilide fumarate given after a waiting period of 20 minutes. Retroperfusion
      of the left atrium could account for these results; in fact the Vein of Marshall
      has no valvular apparatus in contrast with other coronary sinus tributary veins
      which are equipped with an uni- or bicuspidal valve. CONCLUSIONS: Pharmacological
      atrial defibrillation with a minimal dose of an antiarrhythmic drug delivered
      near the orifice of the Vein of Marshall via the temporarily occluded coronary
      sinus is feasible and effective. This new pharmacological atrial defibrillation
      can offer interesting opportunities in developing an implantable pharmacological
      atrial defibrillator.

PMID- 10936001
TI  - Progressive atrioventricular conduction block in a mouse myotonic dystrophy
      model.
AB  - INTRODUCTION: Myotonic dystrophy is caused by expansion of a CTG trinucleotide
      repeat on human chromosome 19, and leads to progressive skeletal myopathy and
      atrioventricular conduction disturbances. A murine model of myotonic dystrophy
      has been designed by targeted disruption of the myotonic dystrophy protein kinase
      (DMPK) gene. The DMPK-deficient mice display abnormalities in A-V conduction
      characteristics, similar to the human cardiac phenotype. The purpose of this
      study was to determine whether age-related progression of A-V block occurs in a
      mouse model of DMPK-deficiency. METHODS AND RESULTS: Surface ECGs and
      intracardiac electrophysiology (EP) studies were performed in 60 immature and 90
      adult homozygous (DMPK-/-), heterozygous (DMPK+/-), and wild-type (WT) DMPK+/+
      control mice. Complete studies were obtained on 141 of 150 mice. The RR, PR, QRS,
      and QT intervals were measured on ECG. Sinus node recovery time, AV refractory
      periods, paced AV Wenckebach and 2:1 block cycle lengths, atrial and ventricular
      effective refractory periods were compared between genotypes and age groups.
      There were no differences in ECG intervals or EP findings in the young mutant
      mice, but progressive PR prolongation in older mice. The A-V conduction defects
      are also sensitive to DMPK gene dosage. Adult DMPK-/- mice develop 1 degrees, 2
      degrees and 3 degrees A-V block, whereas DMPK+/- mice develop only 1 degrees
      heart block. CONCLUSION: These data demonstrate that both age and DMPK dose are
      important factors regulating cardiac conduction in myotonic dystrophy. This mouse
      model of DM is remarkably similar to the human phenotype, with age-related
      progression in atrioventricular conduction defects.

PMID- 10936002
TI  - Parahisian radiofrequency catheter ablation in dogs: comparison of the above
      valve and below-valve approaches.
AB  - In patients with an accessory pathway close to the His bundle, radiofrequency
      catheter ablation (RFCA) requires additional care to avoid damage to the normal
      conduction system. To assess differences between approaches from above or below
      the tricuspid valve (TV), we performed RFCA in 20 dogs (from above, group A,
      n=10; from below, group B, n=10). RF energy with temperature control at 60
      degrees 60 seconds was administered at the site where a small His potential was
      recorded from the ablation catheter guided by fluoroscopy and transesophageal
      echocardiography (TEE) (in the latter six dogs). Before and after RFCA,
      electrophysiological testing was performed and histological findings were
      compared. An ablated lesion was created in 7 of 10 (2 of 2 guided by TEE) dogs in
      group A and 5 of 10 (3 of 4 TEE) dogs in group B. In group A, an ablated lesion
      involved the atrium and ventricle in the anterior site of His bundle, but the
      lesion was only in the ventricle in group B. An atrioventricular block (AVB) and
      severe damage to the penetrating bundle was observed in one dog of group A. A
      large hematoma on the TV was made in 2 dogs and the complete right bundle branch
      block (CRBBB) occurred in 3 dogs of group B. The approach from below the TV was
      safer than that from above the TV in parahisian RFCA, because it did not create
      an AVB, although it has a high incidence of CRBBB and associated technical
      difficulties.

PMID- 10936004
TI  - Electrophysiological heterogeneity of atrial fibrillation and local effect of
      propafenone in the human right atrium: analysis based on symbolic dynamics.
AB  - A recently developed algorithm that is based on symbolic dynamics and computation
      of the normalized algorithmic complexity (C(alpha)) was applied to basket
      catheter mapping of the atrial fibrillation (AF). The aim of our study was to
      analyze the spatial distribution of the C(alpha) during AF and effects of
      propafenone on this distribution. During right atrial mapping in 25 patients with
      AF 31 intra-atrial and 1 surface bipolar channels were acquired. The anatomical
      location of the intra-atrial electrodes was defined fluoroscopically. C(alpha)
      was calculated for a moving window (size: 2000 points; step 500 points).
      Generated C(alpha) was analyzed within 10 minutes before and after administration
      of propafenone. The inter-regional C(alpha) distribution was analyzed using the
      Friedman-test (intra-individually) and Kruskall-Wallis-H-test (inter-
      individually). A value of p=0.05 was set for an error probability. Inter-regional
      C(alpha) differences were found in all patients (p<0.001). The right atrium could
      be divided in high- and low complexity areas according to individual patterns. A
      significant C(alpha) increase in cranio-caudal direction (with the exception of
      septum) was confirmed inter-individually (p<0.01). The administration of
      propafenone enlarged the areas of low complexity. CONCLUSIONS: This new method
      utilizing the combination of symbolic dynamics and adaptive power estimation can
      provide complex evaluation of the dynamics of AF in man. High-density mapping
      will be required for further evaluation of results.

PMID- 10936003
TI  - Clinical relevance of silent atrial fibrillation: prevalence, prognosis, quality
      of life, and management.
AB  - Although first described about 100yr ago, atrial fibrillation (AF) is now
      recognized as the most common of all arrhythmias. It has a substantial morbidity
      and presents a considerable health care burden. Improved diagnosis and an ageing
      population with an increased likelihood of underlying cardiac disease results in
      AF in more than 1% of population. AF is associated with an approximately two-fold
      increase in mortality, largely due to stroke which occurs at an annual rate of 5
      7%. Another risk to survival is heart failure, which is aggravated by poor
      control of the ventricular rate during AF. Usually AF is associated with a
      variety of symptoms: palpitations, dyspnea, chest discomfort, fatigue, dizziness,
      and syncope. Paroxysmal AF is likely to be symptomatic and frequently presents
      with specific symptoms, while permanent AF is usually associated with less
      specific symptoms. However, in at least one third of patients, no obvious
      symptoms or noticeable degradation of quality of life are observed. This
      asymptomatic, or silent, AF is diagnosed incidentally during routine physical
      examinations, pre-operative assessments or population surveys. Recently, a very
      large incidence of generally short paroxysms of AF has been seen in patients with
      implantable pacemakers or defibrillators and these arrhythmias are often silent.
      Pharmacological suppression of arrhythmia may be associated with a conversion
      from a symptomatic to an asymptomatic form of AF. Holter monitoring and
      transtelephonic monitoring studies have demonstrated that asymptomatic episodes
      of AF exceed symptomatic paroxysms by twelve-fold or more. Although symptoms may
      not stem directly from AF, the risk of complications is probably the same for
      symptomatic and asymptomatic patients. AF is found incidentally in about 25% of
      admissions for a stroke. Studies in patients with little or no awareness of their
      arrhythmia condition indicate that unrecognized and untreated AF may cause
      congestive heart failure. In patients with coronary bypass, AF may not only
      represent risk for immediate postoperative morbidity and increase hospital
      resource utilization, but being unrecognized, may produce a significant impact on
      long-term survival and quality of life. Although silent AF merits consideration
      for anticoagulation and rate control therapy according to standard criteria,
      whether antiarrhythmic therapy is relevant in this condition remains unclear.

PMID- 10936005
TI  - Biventricular pacing in end-stage heart failure improves functional capacity and
      left ventricular function.
AB  - BACKGROUND: Asynchronous patterns of contraction and relaxation may contribute to
      hemodynamic and functional impairment in heart failure. In 1993, we introduced
      biventricular pacing as a novel method to treat heart failure by synchronous
      stimulation of the right and left ventricles after an appropriate
      atrioventricular delay. The objectives of this study were to assess the early and
      long-term effects of this therapy on functional capacity and left ventricular
      function in patients with severe heart failure and left bundle branch block.
      METHODS AND RESULTS: Twelve patients with end-stage congestive heart failure,
      sinus rhythm and complete left bundle branch block were treated with
      biventricular stimulation at optimized atrioventricular delay. The NYHA
      functional class and maximal bicycle exercise capacity were assessed. Systolic
      and diastolic left ventricular function were studied with echocardiography and
      radionuclide angiography. Data was collected at various intervals during 1-year
      follow-up. Cumulative survival [95% CI] was 66.7% [40.0,93.4] at 1 year and 50 %
      [21.8, 78.2] at 2 and 3 years. Median NYHA class improved from class IV to class
      II at 1 year (p=0.008). After 6 weeks an increase in exercise capacity occurred,
      which was sustained. A less restrictive left ventricular filling pattern, an
      increase in dP/dt and left ventricular ejection fraction, and a decrease in
      mitral regurgitation were observed early and long-term. CONCLUSIONS:
      Biventricular pacing at optimized atrioventricular delay results in improvement
      in functional capacity, which is associated with improved systolic and diastolic
      left ventricular function, and a decrease in mitral regurgitation during short-
      and long-term follow-up.

PMID- 10936007
TI  - Accuracy of fluoroscopic localization of the Crista terminalis documented by
      intracardiac echocardiography.
AB  - The crista terminalis is an important anatomic target for ablation of atrial
      arrhythmias. We determined the accuracy of catheter placement guided by
      fluoroscopy alone when directed to 24 sites along the crista terminalis in 6
      patients. The sites selected included the most medial superior, most lateral
      superior, mid lateral, and most inferolateral sites along the crista terminalis
      in each patient. These sites were selected because of their recognized importance
      in sinus node and/or atrial tachycardia ablation and the importance of avoiding
      caval structures when targeting the most superior and/or inferior right atrium.
      The position of the catheter tip was documented using a catheter based ultrasound
      transducer in the right atrium or vena cava. The operator was blinded to the
      intracardiac echocardiographic (ICE) results until reviewing the images after the
      procedure in each patient. The catheter tip, guided by fluoroscopy alone, was
      identified by ICE to be within the right atrium and within 1cm of the crista
      terminalis at only 10 of the 24 sites (42%). Importantly, when targeting the most
      superior and inferior sites along the crista terminalis, the catheter tip, guided
      by fluoroscopy, was noted to be adjacent to the venous junction with the right
      atrium but actually located in the superior or inferior vena cava at 5 of the 18
      such sites. The catheter was positioned appropriately (within 1 cm of the crista
      and within the right atrium) guided by fluoroscopy alone when targeting 1 of the
      12 sites in the first 3 patients versus 9 of 12 sites in the last 3 patients,
      p<0.05. In conclusion, it appears that using fluoroscopic guidance alone: 1)
      localization of the crista terminalis is frequently inaccurate and 2) catheter
      positioning in the superior/inferior vena cava is commonly noted when targeting
      very superior and inferior sites along the crista terminalis. A learning curve,
      assisted by review of ICE recordings after each procedure, appears to improve the
      accuracy of catheter placement by fluoroscopy alone but still does not result in
      uniform success. ICE appears to facilitate and ensure accurate targeting of
      specific anatomic sites along the crista terminalis and thus may serve as an
      important adjunctive imaging technique in electrophysiology.

PMID- 10936006
TI  - The importance of right atrial pacing electrode position and pacing configuration
      for intra-atrial and inter-atrial conduction times.
AB  - Pace prevention of atrial tachyarrhythmias is based in part on the reduction of
      intra-atrial (IAA) and/or inter-atrial (IEA) conduction. We previously introduced
      a novel pacing mode using floating atrial ring electrodes on a VDD-lead
      (BIdirectional MO nophasic impulSe: BIMOS). The effects of BIMOS pacing on IAA
      and IEA conduction times has not been studied. In nine Merino sheep electrode
      catheters were placed at the His-Bundle (HBE), high right atrium (HRA), coronary
      sinus ostium (Cs-Os), and left lateral atrium (LLA). A VDD-lead was introduced
      with floating electrodes in the high and mid right atrium (Floating). IAA (S/P
      HRA, S/P-Cs-Os, S/P-HBE, S/P-Floating), IEA conduction times (S/P-LLA), and P
      wave duration (PD) were measured during sinus rhythm (S), during bipolar cathodal
      pacing (P) in the HRA, in the Cs-Os position, as well as during BIMOS floating
      pacing. The mean PD during S was significantly shorter than during HRA- (66. 6+/
      12.8ms; vs. 116.2+/-11.1ms; p<0.05) and Cs-Os-P (66.6+/-12.8ms vs. 94.4+/-9.0ms;
      p<0.05). In comparison to HRA-P, BIMOS configuration lead to a significant
      reduction of the P-wave duration (116.2+/-11.1ms vs. 85. 4+/-8.8ms; p<0.05).
      During BIMOS pacing, the global atrial conduction time was significantly shorter
      than during pacing in the HRA and Cs-Os position. The results of this study
      demonstrate a clear reduction of IAA and IEA conduction times using BIMOS
      configurations compared to conventional HRA-P. Furthermore, BIMOS pacing produced
      a more homogeneous atrial activation when compared with conventional HRA- and Cs
      Os-P.

PMID- 10936009
TI  - Analysis of posterior mitral annular activation during entrainment and catheter
      ablation of mitral isthmus ventricular tachycardia using a coronary sinus
      catheter.
AB  - A detailed analysis of the ventricular activation along the posterior aspect of
      the mitral annulus was made using a multipolar catheter positioned in the
      coronary sinus in a patient with mitral isthmus ventricular tachycardia (VT)
      associated with a remote inferior myocardial infarction and prior cryosurgical
      ablation for the elimination of a different preexisting VT. A change in the
      timing and sequence of the ventricular activation along the isthmus could be
      observed during induction of the VT and entrainment pacing. A radiofrequency (RF)
      current application directed at the posterolateral region of the isthmus
      successfully eliminated this tachycardia. During the RF delivery, complete
      conduction block was confirmed by a sudden change in the activation sequence
      during sinus rhythm.

PMID- 10936008
TI  - Left ventricular tachycardia originating near the left main coronary artery.
AB  - Eight patients with idiopathic ventricular tachycardia (VT) underwent mapping and
      radiofrequency ablation. Mapping showed VT originating in the high posterolateral
      left ventricular outflow tract in proximity to the left main and proximal
      circumflex coronary arteries. Ablation was not attempted due to this proximity to
      the left main and proximal circumflex coronary arteries. Ablation was not
      attempted due to this proximity in 2 patients and limited in 1 patient. It was
      successful in VT suppression in 5 of 6 patients.

PMID- 10936011
TI  - A research agenda for adolescent risk-taking: where do we go from here?

PMID- 10936010
TI  - Catheter ablation of repetitive monomorphic ventricular tachycardia from left
      ventricular outflow tract guided by unipolar mapping.
AB  - Repetitive monomorphic ventricular tachycardia from the left ventricular outflow
      tract is an uncommon arrhythmia. Successful catheter ablation has been previously
      reported in a few cases, but a large number of applications were usually needed
      when an approach based on either activation mapping or pace mapping was used. In
      our patient, the selection of the target point for application was based
      exclusively on unipolar mapping criteria of the ectopic beats, resulting in a
      short procedure with successful outcome.

PMID- 10936012
TI  - Perceptions of the benefits and costs associated with condom use and unprotected
      sex among late adolescent college students.
AB  - To assess the differential effects of the perceived benefits and costs associated
      with both condom use and unprotected sex on sexual risk behaviors, data were
      collected from 704 ethnically diverse male and female sexually experienced late
      adolescent college students (aged 17-25). Perceived benefits and costs for condom
      use and perceived benefits and costs for unprotected sex were measured separately
      through an anonymous self-report survey. In addition, participants completed
      measures of self-efficacy for practicing safer sex and temptation for unsafe sex
      in various situations, and three measures of sexual risk-taking (stage of change
      for condom use, consistency of condom use during the past month, and whether or
      not a condom was used for the last act of intercourse). Univariate analyses
      indicated that benefits and costs of condom use, benefits of unprotected sex,
      self-efficacy and situational temptation were all related to sexual risk-taking.
      Gender differences were identified, with females reporting more benefits of
      condom use and costs of unprotected sex, fewer benefits of unprotected sex and
      costs of condom use, greater self-efficacy for practicing safer sex, and less
      situational temptation for unsafe sex. Multivariate analyses indicated that
      sexual risk behaviors were most related to situational temptation, self-efficacy
      for safer sex, and perceived benefits of unprotected sex. The results suggest
      that, among late adolescents, perceived benefits of the unhealthy behavior
      (unprotected sex) were better determinants of sexual risk-taking than were
      perceived benefits (or costs) associated with the healthy behavior (condom use).
      Perceived costs associated with unprotected sex were unrelated to sexual
      behaviors. These findings support previous work identifying adolescents as more
      driven by their perceptions of the positive benefits associated with risky
      behaviors, rather than knowledge of the costs or dangers involved in risk-taking.

PMID- 10936013
TI  - Adolescent risk-taking and the five-factor model of personality.
AB  - The aim of this study was to investigate the links between adolescent risk-taking
      and personality in a comprehensive manner, as opposed to focusing on any one
      particular risk or personality factor as has occurred in much previous research.
      We conceptualized risk-taking broadly through use of the Adolescent Risk
      Questionnaire (ARQ) which yields information relating to risk judgements and
      behaviours in four areas (i.e. thrill-seeking risk behaviours, reckless risks,
      rebellious risks and antisocial risks). Personality was conceptualized using the
      Five-factor Model of personality, a comprehensive trait model of personality. The
      ARQ and the NEO Five-factor Inventory were administered to 459 school-based
      adolescents aged 11 to 18 years. Consistent with past research, younger
      adolescents and girls generally reported engaging in risk behaviours less
      frequently than older adolescents and boys. Also, younger adolescents and girls
      generally rated the ARQ behaviours as more risky than their older male
      counterparts. This was in line with the significant negative correlations found
      between risk judgements and risk behaviours of all types. Also consistent with
      past research, few age differences were found for the personality traits. Sex
      differences were evident, with female adolescents scoring higher on neuroticism,
      agreeableness and conscientiousness than male adolescents. Together, risk
      judgements, personality factors, age and sex were found to be significant
      predictors of risk behaviours; however, the personality factor of significance
      was found to differ depending upon the risk type. This was also true for age and
      sex which differed in importance depending upon the risk type. Overall, these
      factors were most successful in predicting rebellious risk-taking and least
      successful in predicting thrill-seeking.

PMID- 10936014
TI  - Bridging the gap between moral reasoning and adolescent engagement in risky
      behavior.
AB  - Relations among moral reasoning, domain judgment and engagement in risky
      behaviors were assessed with 68 students attending a Just Community school and
      122 comparison students from the larger high school with which the alternative
      school is affiliated. Risky behaviors were perceived as personal decisions,
      rather than as ones of morality or convention. Engagement and domain judgment of
      risky behavior interacted; with increasing substance involvement, students were
      more likely to view the decision to use drugs and alcohol as a personal decision
      than as either a moral or conventional decision. Domain judgments of risks
      appeared to moderate the relation between moral reasoning and engagement in risky
      behavior, suggesting that moral education interventions must encourage youth to
      explore their views that much of their behavior is only their own business.

PMID- 10936015
TI  - A prospective study of adolescent pregnancy.
AB  - This study examined prospectively the characteristics contributing to adolescent
      pregnancy in a pregnant (n=452) and comparison (n=373) group of adolescents. The
      participants were 15-19-year-old Black and White females in the National
      Longitudinal Survey of Youth. The variables included race, self-esteem, age
      related risks, delinquency history, aspirations and expectations Using regression
      analyses, adolescent pregnancy in Blacks was predicted by approval of delaying a
      family and pursuing a career, aspirations of working, and lower educational
      expectations. Pregnancy in White adolescents was predicted by higher educational
      wishes, lower educational expectations, desiring more children, and having sex
      younger. Implications and recommendations are discussed.

PMID- 10936016
TI  - Targeting adolescent risk-taking behaviors: the contributions of egocentrism and
      sensation-seeking.
AB  - Tremendous resources are spent each year developing programs and messages
      targeting adolescent risk behavior. Adolescents are often reasonably well
      educated about methods for health promotion such as preventing HIV infection, yet
      they fail to act accordingly. One widely used individual difference variable,
      sensation-seeking, has been incorporated in health message design to some extent,
      but it fails to take development into account. Research on adolescent egocentrism
      suggests adolescents experience personal fable which can lead to an exaggerated
      sense of invulnerability. The present study sampled adolescents and college
      students to examine relative contributions of egocentrism and sensation-seeking
      to risk-taking behavior. Results indicate a latent factor labeled risk-seeking
      (primarily indicated by disinhibition and risk-taking personality, and to a
      lesser degree by invulnerability, experience-seeking, boredom susceptibility, and
      thrill and adventure-seeking) indeed predicted a latent factor labeled delinquent
      behavior (primarily indicated by alcohol consumption and delinquency, and to a
      lesser degree by drug use, drinking and driving, and risky driving). Other
      results indicate consistently high personal fable combined with high sensation
      seeking explained most risk-taking behavior. Implications and directions for
      future research are discussed.

PMID- 10936017
TI  - The dangerousness of youth-at-risk: the possibilities of surveillance and
      intervention in uncertain times.
AB  - This paper will explore the dangerous possibilities provoked by the popular and
      promiscuous construction of the category of "youth-at-risk". In an age of large
      scale and profound social changes, narratives of uncertainty and risk dominate
      popular, political and theoretical discourses about youth. Under these social
      conditions, the discourse of youth-at-risk is mobilized from a variety of
      intellectual and political positions in various attempts to regulate the
      behaviors and dispositions of youth. The paper will argue that these discourses
      provoke dangerous possibilities for the increased surveillance of, and
      intervention into, young people's lives by regulatory authorities (schools,
      police, health services, and juvenile justice systems) and the forms of expertise
      recruited by these agencies.

PMID- 10936018
TI  - Gender differences in Ayrshire teenagers' attitudes to sexual relationships,
      responsibility and unintended pregnancies.
AB  - Disadvantages and risks related to teenage pregnancy, together with a recent
      increase in Scottish conception rates among teenagers aged 13-15 years old, give
      cause for concern. Using an illustrated short story and questionnaire, attitudes
      of 129 Ayrshire teenagers aged 14-15 years old were examined to teenage
      pregnancy, and more generally to early sex. Seventy-three percent of girls
      advocated joint responsibility for contraceptive protection compared with only
      46% of boys (p<0.01). Also, significantly more boys than girls saw nothing wrong
      with casual sex (21%vs. 5%, p<0.01), and significantly less boys than girls
      upheld the virtue of commitment in sexual relationships (27%vs. 54%, p<0.01). Sex
      education programmes should explore these gender-related disparities.

PMID- 10936019
TI  - Parental expectations of their adolescents' teachers.
AB  - In spite of increasing parental participation in their children's education, and
      the growing research interest in this trend, the study of one of the central
      components of parental involvement, namely, parental expectations of teachers,
      has been scarce. The present research focuses on this important, albeit
      neglected, topic. We examined the effects of the sex of the parent and the sex
      and grade level of the specific child on parental expectations of teachers. Seven
      hundred and sixty-five Israeli parents of students attending 31 educational
      institutions participated in the study. They completed the Expectations of
      Teachers questionnaire, consisting of 12 items describing behavioural
      characteristics of teachers subsumed under three broad categories: Help and
      Assistance, Teaching Competence, and Fairness. Greater expectations for Help and
      Assistance were reported by the parents, followed by Teaching Competence and
      Fairness on the part of the teacher. Mothers hold higher Fairness and Help and
      Assistance expectations as compared with fathers. Help and competence
      expectations were higher for parents of female students as compared with parents
      of boys. Conclusions from our study call for increasing efforts geared toward the
      building of a sustainable and beneficial partnership between teachers and parents
      for the best interest of the students and for the further elucidation of
      teachers' expectations of parents.

PMID- 10936020
TI  - A test of the validity of delinquency syndrome construct in a homogeneous sample.
AB  - This was a study of 387 adolescents who regularly attended churches affiliated
      with a primary Protestant denomination in a Midwestern state. The purpose was
      twofold: (1) to determine if the delinquency syndrome argument has validity in a
      sample of religious youths, by testing whether the same basic theoretical models
      explained crime and drug use; and (2) to examine the relative utility of
      sociodemographic, social control and social learning factors in explaining these
      two forms of delinquency. The study finds that all theoretical factors
      investigated are correlated significantly with both crime and use of drugs;
      however, some of these factors are differentially related to those two forms of
      delinquency. Also, social control elements did account for more additional
      variance in crime than did social learning or sociodemographic factors.
      Implications for future research are discussed in the context of limitations of
      the present study.

PMID- 10936021
TI  - African-American fathers: perceptions of two generations.
AB  - The purpose of this study was to determine how African-American fathers of 10-14
      years-olds viewed their assets and limitations as parents, and to find out how
      children from this age group saw the parent performance of their fathers. The
      Parent Success Indicator was administered to 102 fathers and to 104 adolescents.
      Significant differences were found between generations on five of six subscales.
      The independent variables entering the greatest effect on how both generations
      perceived parental success were amount of time father and child spent together,
      having an adult at home when a child returns from school, and gender of child.

PMID- 10936022
TI  - Generation and characterization of a clonotypic antibody specific for the T cell
      receptor of an arthritogenic T cell clone--studies in adjuvant arthritis.
AB  - Adjuvant Arthritis (AA) can be induced by passive transfer of a T cell clone
      (A2b) derived from arthritic rats, specific for Heat Shock Protein 60, HSP60 176
      190. Furthermore, a crucial role for T cells with HSP60 176-190 specificity in AA
      was shown by induction of tolerance using HSP60 176-190 or by immunization with
      an altered peptide ligand based on the same sequence. To study clonal expansion
      of A2b-like T cells during AA and to determine their role in AA induction, we
      generated a clonotypic antibody, 16C4, specific for the TCR of the A2b T cell
      clone (TCR AV11S1/BV18). This antibody stained A2b T cells in flow cytometry
      experiments, induced proliferation of A2b cells when fixed on a solid support,
      and inhibited antigen-induced A2b proliferation when added in solution. A2b-like
      T cells were detected in a low frequency in lymphoid organs of arthritic rats.
      Thus, as in vivo administration of 16C4 did not inhibit AA, cells containing the
      determinant recognized by 16C4 are possibly not the sole contributors to AA
      development. Furthermore, epitope specific interventions by antigen
      administration may be possible even in cases where the epitope specific T cell
      clonotype is of low frequency.

PMID- 10936024
TI  - 'LE cells' result from phagocytosis of apoptotic bodies induced by antinuclear
      antibodies.
AB  - Lupus erythematosus (LE) cells are believed to represent phagocytosis by
      granulocytes of cell nuclei whose DNA has been 'depolymerized' and opsonized by
      serum factors, most likely antinuclear antibodies and C3b. Since it is known that
      certain antinuclear antibodies are capable of inducing apoptosis after
      intracellular penetration; and that the resulting apoptotic bodies can be
      ingested by non-professional phagocytes, we decided to investigate the
      possibility that LE cells could result from the phagocytosis of apoptotic bodies
      induced by antinuclear antibodies. We demonstrate herein, through different
      methodological approaches, that the ingested material within LE cells corresponds
      to apoptotic bodies, and that the LE cell phenomenon can be reproduced, in the
      absence of other serum factors, by penetrating murine monoclonal anti DNA
      antibodies.

PMID- 10936023
TI  - Induction of anti-DNA antibodies in preautoimmune NZBxNZW F1 mice by immunization
      with a DNA-DNase I complex.
AB  - Recent studies suggest that anti-DNA antibodies may arise from the immune
      response to a complex of DNA and a DNA-binding protein. One of the protein
      targets frequently recognized by anti-DNA antibodies is the enzyme DNase I. To
      investigate the possible role of DNase I in the induction of anti-DNA antibodies,
      we immunized preautoimmune NZBxNZW F1 mice with a complex of DNA and DNase I
      emulsified in complete Freund's adjuvant. Control mice received DNA or DNase in
      adjuvant. IgG anti-dsDNA antibodies were induced in 50% of the mice immunized
      with DNA-DNase, in 25% of the mice immunized with DNase and in 6% of the mice
      immunized with DNA. However, immunized mice that produced anti-DNA antibodies did
      not develop renal disease. These data show that a DNA-binding protein like DNase
      may act as carrier in the immune response that leads to anti-DNA antibodies
      production in an autoimmune strain, but the induced anti-dsDNA antibodies have a
      low pathogenic potential.

PMID- 10936025
TI  - Phospholipid-bound beta 2-glycoprotein I induces the production of anti
      phospholipid antibodies.
AB  - Apoptotic-cell-bound beta2-glycoprotein I (beta2GPI), but not apoptotic cells or
      beta2GPI alone, can induce the production of anti-phospholipid (anti-PL)
      antibodies (Ab) in normal mice. Although it is presumed that beta2GPI binds to
      anionic phospholipid (PL) exposed on the apoptotic cell membrane, the precise
      nature of this complex and its immunogenicity is unclear. To address these
      issues, we investigated the structure and immunogenicity of human beta2GPI in the
      presence of different PL that may be expressed on the surface of apoptotic cells.
      BALB/c mice were immunized intravenously (iv) with beta2GPI in the presence of
      cardiolipin (CL), phosphatidylglycerol (PG), phosphatidylserine (PS),
      phosphatidylcholine (PC), or PS/PC (25%/75%) vesicles. Cardiolipin+beta2GPI
      induced the highest levels of anti-beta2GPI and anti-CL IgG Ab and lupus
      anticoagulant (LA) activity, while beta2GPI with PC or PS/PC vesicles produced no
      significant anti-PL Ab. PS+beta2GPI was somewhat immunogenic, but less so than
      PG+beta2GPI. beta2GPI was immunogenic in the presence of native (CL(N)), but not
      hydrogenated (CL(H)), CL. Circular dichroism analysis demonstrated that the
      structure of beta2GPI was altered specifically by interaction with CL(N), but not
      other anionic PL, including CL(H). Similarly, the structure of CL(N)was affected
      by interaction with beta2GPI, as detected by(31)P nuclear magnetic resonance.
      These findings demonstrate that beta2GPI complexed with CL(N)is structurally
      altered, highly immunogenic, and induces the production of IgG anti-PL Ab.
      Furthermore, the structural modification and the generation of immunogenic
      epitopes on beta2GPI upon interaction with CL(N)require the presence of
      unsaturated fatty acid chains, suggesting a role for oxidation in this process.

PMID- 10936026
TI  - Identification of mimotopes of platelet autoantigens associated with autoimmune
      thrombocytopenic purpura.
AB  - GPIIb/IIIa, the human platelet glycoprotein complex, is the autoantigen most
      commonly recognized by autoantibodies in autoimmune thrombocytopenic purpura
      (AITP). Two murine monoclonal antibodies (mAbs), namely Y2/51 and 5B12, directed
      against gpIIIa and gpIIb/IIIa, respectively, and rabbit anti-human platelet
      polyclonal antibodies have been used to select AITP-related epitopes from a phage
      display peptide library expressing random dodecapeptides in the pIII coat protein
      of M13 phage. The selected phage clones were tested by ELISA for binding to
      rabbit anti-human platelet antibodies as well as to sera from AITP patients.
      Seven clones reacted strongly with rabbit anti-human platelet antibodies, and
      four clones reacted with sera from AITP patients. Some homology between peptide
      inserts sequences of selected clones and human platelet gpIIIa and gpIb were
      found.

PMID- 10936027
TI  - The identification of endothelial cell autoantigens.
AB  - The identity of many endothelial cell autoantigens remains unclear. This study
      has used human monoclonal anti-endothelial cell autoantibodies isolated from
      patients with SLE to identify endothelial autoantigens. Thirteen antibodies
      reactive with endothelial cell membrane preparations were isolated and cloned,
      one of which has previously been demonstrated to be pro-inflammatory. Western
      blotting demonstrates that these antibodies recognize a variety of proteins in
      endothelial cell membrane preparations. Further characterization of five
      antibodies by cDNA library screening, immunofluorescence and Western blotting
      proves that two of these antibodies recognized the cytoskeletal proteins tubulin
      and vimentin. A further antibody identified a clone derived from human
      collagenase, an identification supported by Western blotting. The multiple clones
      selected by other antibodies are not compatible with the molecular weight of the
      antigen recognized in Western blotting studies. This study has clearly identified
      two endothelial cell autoantigens present in membrane preparations and provides
      strong evidence as to the identity of a third.

PMID- 10936028
TI  - Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti
      lipoic acid antibody in primary biliary cirrhosis: searching for a mimic.
AB  - Previous studies documenting the existence of cross-reactivity between the
      lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2
      [the major autoantigen in Primary biliary cirrhosis (PBC)] and
      trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to
      an initial insult with an environmental agent that cross-reacts with TFA.
      Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA
      antibody and anti-lipoic acid (LA) antibody against the mitochondrial
      autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas
      both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of
      E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non
      lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2,
      TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast,
      anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC
      enzyme activity. Hence, although considerable cross reactivity exists between
      anti-TFA and anti-LA, the molecular nature of the interaction is clearly
      different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14
      PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA
      antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC
      and controls. However, anti-LA produced much stronger focalized staining of the
      bile ducts of diseased liver. This study suggests that while anti-TFA antibody
      recognizes lipoic acid-linked enzymes and proteins, the epitope recognized
      differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that
      a response to TFA is the triggering event in PBC. Anti-LA antibodies share a
      higher degree of similarity to PBC sera providing suggestive evidence that anti
      LA antibodies or anti-LA like antibodies (mimotopes) may help define the
      initiator of the autoimmune response.

PMID- 10936029
TI  - Increased expression of CD40 ligand in activated CD4+ T lymphocytes of systemic
      sclerosis patients.
AB  - CD40-CD154 interactions play a key role in regulating immune response and are
      involved in the development of some autoimmune diseases. We analysed the
      expression of CD154 antigen in CD3-activated PBMC from 10 systemic sclerosis
      (SSc) patients and 10 control subjects by immunofluorescence. PBMC from SSc
      patients showed an increased expression of this molecule, since, 6 h following
      CD3 stimulation, the percentage of CD154(+)cells was of 17. 53+/-2.0 (mean+/-SE)
      in control and 25.33+/-2.93 in patient cells (P< 0.03). The higher expression of
      CD154 antigen was ascribible to CD4(+)cells. The enhanced induction of CD154
      following CD3 stimulation depended on protein synthesis, since was abolished when
      the cells were stimulated via CD3 in the presence of cycloheximide. By analysing
      the expression of the CD40-induced antigen CD80, we verified that a blocking anti
      CD40 antibody inhibited CD80 appearance in SSc activated monocytes, indicating
      that CD154 molecule was functional. These results show an enhanced expression of
      a functional CD154 molecule in SSc CD4(+)activated T lymphocytes.

PMID- 10936030
TI  - HLA class II polymorphism contributes to specify desmoglein derived peptides in
      pemphigus vulgaris and pemphigus foliaceus.
AB  - Susceptibility to Pemphigus, an autoimmune disease of the skin, has been
      previously linked to DRB1*0402, 1401/04 and DQB1*0503 in pemphigus vulgaris (PV),
      to DRB1*0102, 0404, 1402/06 in endemic pemphigus foliaceus in Brazil and to
      DRB1*04 in Italian patients suffering from pemphigus foliaceus (PF). The disease
      is caused by autoantibodies against desmoglein (Dsg1 in PF, Dsg3 in PV).
      Molecular typing of 57 French patients suffering from PV (37) and from PF (20)
      confirmed previous results concerning PV and showed that DRB1*0102 and 0404 are
      susceptible molecules to PF in France. We have analysed the characteristics of
      the 'pockets' of the susceptibility-associated molecules to PV and PF and we
      showed that (i) in PV, two kinds of Dsg3 derived peptides may be presented by HLA
      DR according to HLA polymorphism (DRB1*0402 or DRB1*14/0406), (ii) the same Dsg1
      peptides may be presented by DRB1*0102, DQB1*0404 or DRB1*14 in PF, (iii) the
      DRB1*14/0406 PV-related molecules may be able to present Dsg1 and Dsg3 peptides
      thereby providing an explanation for the cases of PV with combined responses to
      Dsg1 and to Dsg3 which are typified by a muco-cutaneous clinical phenotype.

PMID- 10936031
TI  - Identification of human autoantibodies to the transcriptional repressor ZF5.
AB  - ZF5 was originally cloned as a transcriptional repressor on the mouse c-myc
      promoter. It contains the Kruppel-type zinc fingers and a conserved POZ domain,
      which is found in a growing number of zinc finger proteins and mediate protein
      protein interactions. Autoantibodies against transcription factors are sometimes
      found in sera from patients with high levels of anti-nuclear antibody (ANA).
      Using Western blotting with ZF5 and sera of autoimmune disease, we detected one
      serum, named M6 serum, which contains the antibody against a transcriptional
      repressor ZF5. The confirmed epitope was specific to ZF5 and was not reactive to
      the other analogous factors: BCL-6, ZID, and Sp1. This epitope also has a
      molecular mimicry of the viral proteins. From these results, we predict that
      viral protein which mimics host ZF5 antigen triggers self-reactive T cell clones
      and induces the autoantibody in M6 serum after the destruction of host tissues.

PMID- 10936032
TI  - Gonadotropin-releasing hormone (GnRH) variants in a lizard brain: is mammalian
      GnRH being expressed?
AB  - In reptiles as in other vertebrates, multiple forms of gonadotropin-releasing
      hormone (GnRH) within a single brain have been identified. In this group the
      following GnRH molecular variants have been characterized either by direct or
      indirect methods: chicken GnRH I (cGnRH-I), chicken GnRH II (cGnRH-II), salmon
      GnRH (sGnRH) and several unidentified GnRH-like forms. In the present study GnRH
      variants were investigated in brain extracts of the lizard Tupinambis teguixin (=
      T. merinae) by combining high-performance liquid chromatography (RP-HPLC)
      followed by radioimmunoassays (RIA). Two peaks showing GnRH immunoreactivity with
      the elution position of synthetic mammalian GnRH (mGnRH) and cGnRH-II were
      detected. Both peaks were further analyzed with different radioimmunoassay
      systems specific for mGnRH, cGnRH-I, and cGnRH-II. Pooled fractions corresponding
      to the first eluting peak showed no crossreactivity when analyzed with a cGnRH-I
      specific assay and logit-log displacement curves were not significantly different
      from those of synthetic mGnRH with homologous RIA systems. The second peak showed
      immunological characteristics of cGnRH-II when analyzed with a specific
      antiserum. The first ir-GnRH peak was selected for further RP-HPLC purification
      showing similar chromatographic behavior as mGnRH synthetic standard. We
      demonstrated the absence of cGnRH-I in this lizard using well-characterized
      antisera.

PMID- 10936033
TI  - Sequence analysis and androgen regulation of MHG07 (Male harderian gland) mRNA in
      male hamster harderian gland.
AB  - The hamster Harderian gland (HG), a compound tubuloalveolar gland located in the
      orbital cavity, displays sex dimorphism. The present study focuses on the
      sequence analysis of a cDNA clone named MHG07 and on the regulation of its
      expression by steroid hormones. MHG07 mRNA (5.0 kb) is expressed in male HG only.
      The MHG07 cDNA (1.74 kb) shows an ORF of 94 amino acids and has no significant
      homologies with other polypeptides/genes. Castration leads to the disappearance
      of MHG07 mRNA after 4 days, whereas treatment with testosterone impairs the
      effect of castration. No MHG07 mRNA has been found in either rat or murine HGs.
      Androgen (A) administration to female hamsters induces the appearance of MHG07
      mRNA. In primary culture of male hamster HG, androgens increase the MHG07
      expression and this effect is blocked by both flutamide and cycloheximide. Dose
      response experiments show that, at low A concentration (10(-12) M), the MHG07 was
      higher than that of the control (2-fold). This effect reaches its zenith at 10(
      8) M (10-fold). This picture is paralleled by androgen receptor mRNA expression.
      It is argued that the expression of MHG07 is under androgenic control.

PMID- 10936034
TI  - The expression of the sex steroid-synthesizing enzymes CYP11A1, 3beta-HSD, CYP17,
      and CYP19 in gonads and adrenals of adult and developing zebra finches.
AB  - Songbirds have emerged as important animal models for understanding how sex
      steroids influence brain and behavior, particularly how they direct the sexually
      dimorphic development of the neural circuits controlling song and then activate
      adult song behavior. Presumably, sex steroids synthesized in the gonads are
      responsible for these actions on brain. However, experiments do not always reveal
      a direct relationship between gonadal function, circulating sex steroids, and
      activation and/or organization of song. Thus, it is critical that we understand
      more about the sites and mechanisms of sex steroid synthesis in this group of
      birds. Toward this end, we have established the use in zebra finches of chicken
      cDNA probes to the principal androgen synthetic enzymes, CYP11A1, 3beta-HSD, and
      CYP17. On Northern blots, these probes recognized bands of the appropriate size
      and in tissues similar to those seen in chickens. With these probes, and a probe
      to CYP19 specific to the zebra finch, we used in situ hybridization to examine
      the cellular expression of these enzymes in gonads and adrenals of adult and
      developing zebra finches (1 to 20 days posthatching). In adults, we identified
      significant expression of CYP11A1 and CYP17 in large ovarian follicles,
      particularly the thecal cell layer and over the testicular interstitial area.
      3beta-HSD was expressed by both theca and granulosa and in testicular
      interstitial and seminiferous tubular cells. In adrenals, CYP11A1 and 3beta-HSD
      are abundant with lesser amounts of CYP17. Developmentally, we identified high
      expression of CYP11A1 and 3beta-HSD in the adrenals, CYP17 in both testes and
      ovaries, and CYP19 in ovaries only. These results suggest that the ovaries but
      not the testes may secrete estrogen developmentally and the adrenals may
      contribute precursors for gonadal steroidogensis.

PMID- 10936035
TI  - Pituitary proopiomelanocortin-derived peptides and hypothalamus-pituitary
      interrenal axis activity in gilthead sea bream (Sparus aurata) during prolonged
      crowding stress: differential regulation of adrenocorticotropin hormone and alpha
      melanocyte-stimulating hormone release by corticotropin-releasing hormone and
      thyrotropin-releasing hormone.
AB  - Plasma levels of cortisol, growth hormone (GH), adrenocorticotropin hormone
      (ACTH), alpha-melanocyte-stimulating hormone (alpha-MSH), N-acetyl-beta
      endorphin, in vitro ACTH-stimulated cortisol secretion, and in vitro
      corticotropin-releasing hormone (CRH)- and thyrotropin-releasing hormone (TRH)
      stimulated ACTH and alpha-MSH secretion were investigated in gilthead sea bream
      exposed to high stocking density (30 kg m(-3)) for 23 days. Within 3 days after
      the onset of crowding, plasma levels of cortisol, ACTH, alpha-MSH, and N-acetyl
      beta-endorphin were above control values. After 7 days, plasma parameters had
      returned to control levels, but at 23 days, cortisol, alpha-MSH, and N-acetyl
      beta-endorphin levels were again elevated over controls, indicating a long-term
      activation of the melanotrope cells. In contrast, crowding stress elicited a
      prolonged reduction in plasma GH levels concomitant with the increased
      hypothalamus-pituitary-interrenal axis (HPI) activation. Crowding stress enhanced
      cortisol secretory activity of the unstimulated interrenal cells. However,
      interrenal tissue from crowded fish in vitro displayed an attenuated response to
      ACTH stimulation compared with tissue from control fish, indicating a
      desensitization of these cells to ACTH during crowding. The involvement of
      pituitary proopiomelanocortin-derived peptides in the HPI axis of sea bream is
      indicated by the observed modulation of the CRH and TRH responsiveness of the
      corticotropes and melanotropes in crowded fish. At day 1, when there were
      crowding-induced plasma increases in ACTH and alpha-MSH, there was an attenuated
      CRH-stimulated but not TRH-stimulated, ACTH release. However, at that time, CRH-
      and TRH-induced responses of alpha-MSH secretion, and the unstimulated secretory
      activity of the MSH cells, were enhanced in crowded sea bream. These data provide
      evidence for stimulatory roles of multiple hypothalamic (CRH and TRH) and
      pituitary (ACTH and alpha-MSH) peptides in the activation of the hypothalamus
      pituitary-interrenal axis under crowding conditions in sea bream.

PMID- 10936036
TI  - Human chorionic gonadotropin-induced spermiation in Bufo arenarum is not mediated
      by steroid biosynthesis.
AB  - This study employed an in vitro system to identify potential steroidal mediators
      of spermiation in Bufo arenarum. Testicular fragments were incubated for 2 h at
      28 degrees. Spermiation was induced by 10 IU human chorionic gonadotropin (hCG)
      and the effect of different inhibitors of steroid biosynthesis was analyzed.
      Cyanoketone (10(-5)-10(-6) M), an inhibitor of 3-oxo-4-ene steroid biosynthesis,
      did not block hCG-inducing activity even when biosynthesis of 3-oxo-4-ene
      steroids and its reduced metabolites was inhibited by 95%. Aminogluthetimide at a
      concentration that inhibited testosterone biosynthesis (10(-4) and 10(-5) M) did
      not alter hCG actions. Similar results were obtained with spironolactone, an
      inhibitor of 17alpha-hydroxylase/17-20 lyase activity. No spermiation-inducing
      activity was found with different steroids (progesterone, 17-hydroxypregnenolone,
      17, 20alpha/beta-dihydroxy-4-pregnene-3-one, estradiol, testosterone, etc.). It
      is concluded that spermiation induced by hCG is not steroid mediated in B.
      arenarum.

PMID- 10936037
TI  - Changes in thyroid hormones in the serum and the thyroid gland of hibernating
      frogs, Rana temporaria L.
AB  - The hypothalamo-pituitary-gonadal axis spontaneously activates in hibernating
      frogs, Rana temporaria, under constant conditions (0-4 degrees, darkness). The
      hypothesis that the spontaneous hibernatory activation involves other regulatory
      processes preparing the frogs for breeding and posthibernatory activity was
      tested. The serum concentrations and glandular contents of thyroid hormones (THs)
      were determined during hibernation. It was shown that (i) in both sexes, serum
      thyroxine and triiodothyronine levels significantly increased in the middle of
      January (week 13/14, between day 92 and 98 of hibernation); (ii) the peak of THs
      blood concentration was accompanied by a slow decrease of free forms of THs and
      the bound forms of both hormones dropped rapidly over this period; (iii) after a
      decrease on day 111, the low level of serum THs (but higher than before the peak)
      was sustained to the end of hibernation; (iv) the thyroid content of free THs
      significantly rose after their "surge" into the blood, reached maximal values in
      the middle of February, and remained at this level to the end of hibernation
      (last week of March); (v) in spring, after spawning, the THs levels in glands and
      in serum were much lower than those at the end of hibernation or were not
      detectable; and (vi) the results were confirmed during the second season, when
      the material in the period of expected elevation of serum THs was collected every
      other day.

PMID- 10936038
TI  - Molecular cloning and tissue-specific expression of a gonadotropin-releasing
      hormone receptor in the Japanese eel.
AB  - Gonadotropin-releasing hormone (GnRH) is a key regulatory neuropeptide involved
      in the control of reproduction in vertebrates. In the Japanese eel, one of the
      most primitive teleost species, two molecular forms of GnRH, mammalian-type GnRH
      and chicken-II-type GnRH (cGnRH-II), have been identified. This study has
      isolated a full-length cDNA for a GnRH receptor from the pituitary of the eel.
      The 3233-bp cDNA encodes a 380-amino acid protein which contains seven
      hydrophobic transmembrane domains and N- and C-terminal regions. The exon/intron
      organization of the open reading frame of the eel GnRH receptor gene was also
      determined. The open reading frame consists of three exons and two introns. The
      exon-intron splice site is similar to that of the GnRH receptor genes of mammals
      reported so far. Expression of the eel GnRH receptor was detected in various
      parts of the brain, pituitary, eye, olfactory epithelium, and testis. This result
      suggests that GnRH has local functions in these tissues in addition to its
      actions on gonadotropin synthesis and release in the pituitary. This tissue
      specific expression pattern is similar to that of the eel cGnRH-II. Furthermore,
      the present eel receptor shows very high amino acid identity with the catfish and
      goldfish GnRH receptors, which are highly selective for the cGnRH-II. These
      results suggest that the cGnRH-II acts through binding to the present receptor in
      the eel.

PMID- 10936039
TI  - Development of the corticosterone stress response in young northern mockingbirds
      (Mimus polyglottos).
AB  - In birds, additional adrenocortical secretion in response to stressors often
      redirects an individual's ongoing activities toward immediate life-saving
      activities, usually by facilitating an increase in food searching and food intake
      needed to meet periods of increased energy demand. We asked whether young birds,
      who are entirely dependent on parents for food acquisition and therefore unable
      to manipulate their own food intake, fail to show an adult-like adrenocortical
      response to the acute stress of capture and handling. In 1998, plasma profiles of
      acute corticosterone secretion (e.g., samples taken at the time of capture and 30
      min later) were compared across seven age classes of Northern Mockingbirds (Mimus
      polyglottos) representing various age-related stages of foraging ability and
      opportunity. As predicted, young birds less able, or entirely unable, to readjust
      their own foraging effort exhibited significantly lower stress responses compared
      to adults. The magnitude of the stress response (at 30 min postcapture) increased
      and approached that of adults as young birds approached independence. Energetic
      condition was not correlated with the magnitude of the stress response at any
      age, suggesting that variation in its expression was most likely due to age
      alone. We also investigated at what level within the hypothalamic-pituitary
      adrenal (HPA) axis the corticosterone response may be controlled in young birds.
      In 1999, baseline corticosterone samples were taken in 8-day-old nestlings and
      were immediately followed by intrajugular injections of adrenocorticotropic
      hormone (ACTH) or saline. While plasma corticosterone concentrations did not
      change in saline-injected nestlings, ACTH-injected nestlings showed a significant
      increase in plasma corticosterone concentrations similar to 30-min samples taken
      from adults. These results indicate that, while young birds do not normally show
      the corticosterone response, the adrenocortical tissue has the capacity to do so,
      and the control appears to be within the hypothalamic-pituitary component of the
      HPA axis. Collectively, our results indicate that the expression of the
      corticosterone stress response develops in concert with a young, altricial bird's
      ability to utilize it as it approaches independence; the reduced corticosterone
      secretion may also allow young, rapidly growing birds to avoid potential
      deleterious exposure to elevated glucocorticosteroid concentrations.

PMID- 10936040
TI  - Aromatase activity during embryogenesis in the brain and adrenal-kidney-gonad of
      the red-eared slider turtle, a species with temperature-dependent sex
      determination.
AB  - Gonadal sex in the red-eared slider turtle is determined by the incubation
      temperature that the embryo experiences during the mid-trimester of development.
      High temperatures result in female-biased sex ratios, and low temperatures
      produce male-biased sex ratios. The physiological equivalent of temperature
      appears to be a combination of the nature and abundance of steroidogenic enzymes
      and their products-including estradiol and its precursor, testosterone-and
      aromatase, the enzyme that converts testosterone to estradiol. Aromatase has been
      hypothesized to play a major role in the female developmental pathway in this
      species, and research in other species with temperature-dependent sex
      determination points to the brain as an organ that transduces the temperature
      signal into an aromatase response. In this study, we used a tritiated water assay
      to compare the pattern of estradiol biosynthesis at male- and female-producing
      temperatures in the brain and adrenal-kidney-gonad (AKG) through development. The
      pattern for both sexes in the AKG was one of increased activity after the
      temperature-sensitive period (TSP), but with no significant difference between
      sexes. In the brain, however, putative females exhibited a significantly higher
      level of aromatase activity than putative males at the beginning of the TSP,
      after which activity in both male and female brains decreased, dropping below
      detection in females before hatch. These results point to the brain as a site of
      aromatase response to temperature in this species, and they suggest that the
      product of aromatase activity, estradiol, may induce alterations in the
      neuroendocrine axis controlling gonadal sex steroid hormone production.

PMID- 10936041
TI  - Molecular cloning of the chicken prolactin gene and activation by Pit-1 and cAMP
      induced factor in GH3 cells.
AB  - Transcription of the prolactin (PRL) gene has been reported to be activated by a
      nuclear factor, Pit-1. However, the precise molecular mechanisms of the Pit-1
      mediated PRL gene activation are still unclear. We have cloned the chicken PRL
      (cPRL) gene and its 5'-flanking region to analyze their structure and
      transcription-initiating mechanism. In luciferase assay, forskolin activated the
      proximal promoter region between -248 and -76 to transcribe the cPRL gene in GH3
      cells, although there is no canonical cyclic AMP-responsive element in the
      promoter region. In gel mobility shift assay, a DNA fragment between -104 and -76
      containing a putative Pit-1 binding site was bound by nuclear factors from the
      GH3 cells. Furthermore, it was observed that Pit-1 protein specifically bound to
      the DNA fragment in the supershift assay. These results indicate that both Pit-1
      and cAMP-induced factor(s) associated with the cis element on the proximal
      promoter region to activate cPRL gene expression in GH3 cells.

PMID- 10936043
TI  - Cloning of bullfrog thyroid-stimulating hormone (TSH) beta subunit cDNA:
      expression of TSHbeta mRNA during metamorphosis.
AB  - A thyroid-stimulating hormone beta subunit (TSHbeta) cDNA encoding both signal
      peptide and mature TSHbeta molecule was cloned from a cDNA library constructed
      from total RNA of the bullfrog (Rana catesbeiana) adenohypophysis. The bullfrog
      TSHbeta mRNA was estimated by Northern blot analysis to be approximately 1 kb.
      The deduced amino acid sequence showed 40-61% homologies with the sequences of
      TSH beta subunits of other vertebrates. Using the cDNA as a probe, we measured
      changes in mRNA expression in metamorphosing tadpoles of R. catesbeiana. The TSH
      beta subunit mRNA level increased progressively throughout prometamorphic stages,
      reaching its maximum at the end of prometamorphosis. The maximum level was
      maintained throughout early and mid climax, declining at late climax. These
      results, together with previously obtained data on plasma prolactin and pituitary
      prolactin mRNA levels, as well as thyroid hormone levels, are discussed in
      relation to metamorphic changes occurring in the bullfrog larvae.

PMID- 10936042
TI  - Prolonged fasting increases the response of the renin-angiotensin-aldosterone
      system, but not vasopressin levels, in postweaned northern elephant seal pups.
AB  - The 8- to 12-week postweaning fast exhibited by northern elephant seal pups
      (Mirounga angustirostris) occurs without any apparent deleterious effects on
      fluid and electrolyte homeostasis. However, during the fast the role of
      vasopressin (AVP) has been shown to be inconclusive and the involvement of the
      renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine
      the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned
      pups were serially blood-sampled during the first 49 days of their fast. Fasting
      did not induce significant changes in ionic or osmotic concentrations, suggesting
      electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and
      remained depressed, suggesting a lack of dehydration. Aldosterone and plasma
      renin activity exhibited a correlated, linear increase over the first 49 days of
      the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over
      the fast with a peak at day 35, suggesting a shift in the sensitivity of the
      kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but
      concentrations were relatively low. RAAS was modified during the postweaning fast
      in pups and appears to play a significant role in the regulation of electrolyte
      and, most likely, water homeostasis during this period.

PMID- 10936044
TI  - GnRH but not warm temperature induces recrudescence of quiescent testes in the
      tropical lizard Calotes versicolor (Daud.) during postbreeding phase.
AB  - The effects of temperature and various doses of GnRH on testicular recrudescence
      were studied in Calotes versicolor during the postbreeding (December-January)
      resting phase. Adult lizards (n = 51) were segregated into seven groups. Group I
      served as the initial control. Groups II, III, and IV were maintained at room
      temperature (23 +/- 1 degrees, range 17.5-25.5 degrees ) and natural photoperiod
      (12.25 h light:11.35 h dark). Groups V, VI, and VII were maintained at 30 +/- 1
      degrees in an environmental chamber with 12 h light:12 h dark. Groups II and V
      received 0.2 ml saline, groups III and VI received 0.1 microgram GnRH/0.2 ml
      saline, and groups IV and VII received 0.5 microgram GnRH/0.2 ml saline on
      alternate days for 30 days. In the two groups that received 0.5 microgram GnRH,
      there was a significant increase in the diameter of the seminiferous tubules and
      Leydig cell nuclei, 3beta-HSDH activity in Leydig cells, and plasma testosterone
      level compared to those in other groups. There was no evidence of testicular
      recrudescence in lizards exposed to room/high temperatures treated with saline or
      0.1 microgram GnRH. This study of C. versicolor shows that during the resting
      phase, high temperature per se does not stimulate testicular recrudescence,
      whereas 0.5 microgram GnRH does so. Also, the findings suggest that either higher
      brain centers regulating hypothalamus or hypothalamus itself become dormant,
      causing testicular inactivity (inactivation of hypophysial-testicular axis)
      during the postbreeding resting phase.

PMID- 10936045
TI  - A genetic linkage map of the baboon (Papio hamadryas) genome based on human
      microsatellite polymorphisms.
AB  - A first-generation genetic linkage map of the baboon (Papio hamadryas) genome was
      developed for use in biomedical and evolutionary genetics. Pedigreed baboons (n =
      694) were selected from the breeding colony maintained by the Southwest
      Foundation for Biomedical Research. To facilitate comparison with the human
      genome, the baboon linkage map consists primarily of human microsatellite loci
      amplified using published human PCR primers. Genotypes for 325 human
      microsatellites and 6 novel baboon microsatellites were used in linkage analyses
      performed with the MultiMap expert system. The resulting sex-averaged meiotic
      recombination map covers all 20 baboon autosomes, with average spacing among loci
      of 7.2 cM. Direct comparison among homologous (orthologous) loci reveals that,
      for 7 human autosomes, locus order is conserved between humans and baboons. For
      the other 15 autosomes, one or more rearrangements distinguish the two genomes.
      The total centimorgan distances among homologous markers are 28.0% longer in the
      human genome than in the baboon, suggesting that rates of recombination may be
      higher in humans. This baboon linkage map is the first reported for any nonhuman
      primate species and creates opportunities for mapping quantitative trait loci in
      baboons, as well as for comparative evolutionary analyses of genome structure.

PMID- 10936046
TI  - A novel imprinted gene, HYMAI, is located within an imprinted domain on human
      chromosome 6 containing ZAC.
AB  - Transient neonatal diabetes mellitus (TNDM) is a rare disease characterized by
      intrauterine growth retardation, dehydration, and failure to thrive due to a lack
      of normal insulin secretion. This disease is associated with paternal uniparental
      disomy or paternal duplication of chromosome 6, suggesting that the causative
      gene(s) for TNDM is imprinted. Recently, Gardner et al. (1999, J. Med. Genet. 36:
      192-196) proposed that a candidate gene for TNDM lies within chromosome 6q24.1
      q24.3. To find human imprinted genes, we performed a database search for EST
      sequences that mapped to this region, followed by RT-PCR analysis using
      monochromosomal hybrid cells with a human chromosome 6 of defined parental
      origin. Here we report the identification of a novel imprinted gene, HYMAI. This
      gene exhibits differential DNA methylation between the two parental alleles at an
      adjacent CpG island and is expressed only from the paternal chromosome. A
      previously characterized imprinted gene, ZAC/LOT1, is located 70 kb downstream of
      HYMAI and is also expressed only from the paternal allele. In the pancreas, both
      genes are moderately expressed. HYMAI and ZAC/LOT1 are therefore candidate genes
      involved in TNDM. Furthermore, the human chromosome 6q24 region is syntenic to
      mouse chromosome 10 and represents a novel imprinted domain.

PMID- 10936047
TI  - Four DAZ genes in two clusters found in the AZFc region of the human Y
      chromosome.
AB  - The DAZ genes are candidate fertility factors that lie within the human Y
      chromosome's AZFc region, whose deletion is a common cause of spermatogenic
      failure. The number of DAZ genes has been difficult to determine, in part because
      the nucleotide sequences of the DAZ genes are nearly identical. Here,
      fluorescence in situ hybridization and characterization of BAC clones revealed
      four full-length DAZ genes on the human Y chromosome. They exist in two clusters,
      each comprising an inverted pair of DAZ genes (3' <-- 5'::5' --> 3'). Analysis of
      genomic sequences and testicular transcripts suggested that three or four DAZ
      genes are translated. Each gene contains at least seven tandem copies of a
      previously described, 2.4-kb repeat unit that encodes 24 amino acids. In
      addition, two DAZ genes contain tandem copies of a 10.8-kb repeat unit that
      encodes the RNA-binding domain, which appears to be multimerized in some DAZ
      proteins. Combining our present results with previous studies, we can reconstruct
      several steps in the evolution of the DAZ genes on the Y chromosome. In the
      ancestral Y-chromosomal DAZ gene, amplification of both intragenic repeats began
      before the human and cynomolgus (Old World) monkey lineages diverged. During
      subsequent evolution, an inverted duplication of this modified gene occurred.
      Finally, the resulting two-gene cluster was duplicated, generating the two
      cluster/four-gene arrangement found on modern human Y chromosomes.

PMID- 10936048
TI  - A sequence-ready BAC clone contig of human chromosome 10p15 spanning the loss of
      heterozygosity region in glioma.
AB  - Deletion of chromosome 10 is one of the most common chromosomal alterations in
      glioma. At 10p15, the telomeric region of the short arm of chromosome 10, loss of
      heterozygosity (LOH) has been frequently observed by microsatellite analysis,
      suggesting the presence of a tumor suppressor gene. We examined LOH in 34 gliomas
      on chromosome 10, and frequent LOH on 10p was detected on 10p15, in agreement
      with deletion mapping studies on chromosome 10. We then constructed a bacterial
      artificial chromosome (BAC) clone contig covering the critical region, which
      spanned the interval between D10S249 and D10S533 on 10p15. The map contained 68
      BAC clones connected by 74 sequenced tag sites (STSs) and covered approximately
      2.7 Mb, with one gap. A total of 74 STSs, including 6 microsatellite markers, 29
      expressed sequenced tags (ESTs), and 39 BAC end STSs, were physically arranged.
      Twenty-eight ESTs were mapped in the interval between D10S249 and D10S559
      (approximately 1200 kb), and another EST was mapped in the interval between
      D10S559 and D10S533 (approximately 1300 kb). This sequence-ready BAC clone contig
      map will be a basic resource for high-quality sequencing and positional cloning
      of the putative tumor suppressor gene at 10p15 in glioma.

PMID- 10936049
TI  - Cloning and analysis of the mouse Fanconi anemia group A cDNA and an overlapping
      penta zinc finger cDNA.
AB  - Despite the cloning of four disease-associated genes for Fanconi anemia (FA), the
      molecular pathogenesis of FA remains largely unknown. To study FA complementation
      group A using the mouse as a model system, we cloned and characterized the mouse
      homolog of the human FANCA cDNA. The mouse cDNA (Fanca) encodes a 161-kDa protein
      that shares 65% amino acid sequence identity with human FANCA. Fanca is located
      at the distal region of mouse chromosome 8 and has a ubiquitous pattern of
      expression in embryonic and adult tissues. Expression of the mouse cDNA in human
      FA-A cells restores the cellular drug sensitivity to normal levels. Thus, the
      expression pattern, protein structure, chromosomal location, and function of
      FANCA are conserved in the mouse. We also isolated a novel zinc finger protein,
      Zfp276, which has five C(2)H(2) domains. Interestingly, Zfp276 is situated in the
      Fanca locus, and the 3'UTR of its cDNA overlaps with the last four exons of Fanca
      in a tail-to-tail manner. Zfp276 is expressed in the same tissues as Fanca, but
      does not complement the mitomycin C (MMC)-sensitive phenotype of FA-A cells. The
      overlapping genomic organization between Zfp276 and Fanca may have relevance to
      the disease phenotype of FA.

PMID- 10936050
TI  - The cloning and nucleotide sequence of human ST2L cDNA.
AB  - The ST2 gene is a member of the IL-1 receptor family and is hypothesized to be
      involved in helper T cell function, but its functional ligand and physiological
      role remain unknown. We have cloned the human ST2L cDNA that encodes a distinct
      type of membrane-bound ST2 protein. The predicted 556-amino-acid sequence showed
      67% identity to the mouse ST2L protein. The human ST2 gene (IL1RL1) contains 13
      exons and spans 40 kb in length. Its exon-intron organization was elucidated from
      a registered human genomic sequence derived from chromosome 2q, which contains
      three other genes belonging to the IL-1 receptor family in an approximately 202
      kb genomic region. The tissue distribution of ST2 expression was examined by RT
      PCR, and the soluble form (ST2, IL1RL1-a) and ST2L (IL1RL1-b) appear to be
      expressed differentially. We also established stable transfectants of a human
      glioblastoma cell line, T98G, that express human ST2L constitutively, and we
      confirmed cell-surface expression of human ST2L protein on the transfectants.

PMID- 10936051
TI  - The RS447 human megasatellite tandem repetitive sequence encodes a novel
      deubiquitinating enzyme with a functional promoter.
AB  - We have recently identified a tandem repetitive DNA sequence that we designated
      the RS447 megasatellite. In this study, we describe a functional novel
      deubiquitinating enzyme (USP17, 60 kDa) gene that is intronless and encoded by
      the RS447 repeating unit. Northern blot analysis in conjunction with 5' and 3'
      rapid amplification of cDNA ends confirmed the presence of poly(A)(+) containing
      RS447 RNA in normal cells. We also identified a functional promoter sequence as
      well as an open reading frame within every RS447 repeat. When USP17 was expressed
      in Escherichia coli, it exhibited deubiquitinating activity in vivo. An antibody
      against USP17 detected USP17 protein in human cells. Our results indicate that
      the RS447 repeating unit on this megasatellite repeat codes for and actively
      expresses a functional deubiquitinating enzyme. Although it is expressed
      ubiquitously in human tissues, USP17 exhibited a unique expression pattern in
      that its complementary strand is transcribed as an antisense transcript that may
      modulate the level of USP17 expression in the human brain.

PMID- 10936052
TI  - Identification of two novel mammalian genes establishes a subfamily of KH-domain
      RNA-binding proteins.
AB  - We have identified two novel human genes encoding proteins with a high level of
      sequence identity to two previously characterized RNA-binding proteins, alphaCP-1
      and alphaCP-2. Both of these novel genes, alphaCP-3 and alphaCP-4, are predicted
      to encode proteins with triplicated KH domains. The number and organization of
      the KH domains, their sequences, and the sequences of the contiguous regions are
      conserved among all four alphaCP proteins. The common evolutionary origin of
      these proteins is substantiated by conservation of exon-intron organization in
      the corresponding genes. The map positions of alphaCP-1 and alphaCP-2 (previously
      reported) and those of alphaCP-3 and alphaCP-4 (present report) reveal that the
      four alphaCP loci are dispersed in the human genome; alphaCP-3 and alphaCP-4
      mapped to 21q22.3 and 3p21, and the respective mouse orthologues mapped to
      syntenic regions of the mouse genome, 10B5 and 9F1-F2, respectively. Two
      additional loci in the human genome were identified as alphaCP-2 processed
      pseudogenes (PCBP2P1, 21q22.3, and PCBP2P2, 8q21-q22). Although the overall
      levels of alphaCP-3 and alphaCP-4 mRNAs are substantially lower than those of
      alphaCP-1 and alphaCP-2, transcripts of alphaCP-3 and alphaCP-4 were found in all
      mouse tissues tested. These data establish a new subfamily of genes predicted to
      encode closely related KH-containing RNA-binding proteins with potential
      functions in posttranscriptional controls.

PMID- 10936053
TI  - Characterization of the human TBX20 gene, a new member of the T-Box gene family
      closely related to the Drosophila H15 gene.
AB  - T-box transcription factors contain a novel type of DNA-binding domain, the T-box
      domain, and are encoded by an ancient gene family. Four T-box genes, omb, Trg,
      org-1, and H15, have been identified in Drosophila, whereas in mammals the T-box
      gene family has expanded, and 12 human T-box genes have been isolated. We have
      identified a new human T-box gene, TBX20, and its mouse homologue Tbx20, which
      are more closely related to the Drosophila H15 gene than to any known vertebrate
      gene. H15 expression in leg imaginal discs correlates with commitment to a
      ventral fate, implicating this gene in early patterning events. We find that
      TBX20 is expressed in the fetal heart, eye, and limb, and during embryogenesis in
      the mouse, Tbx20 is expressed in the developing heart, eye, ventral neural tube,
      and limbs, indicating a possible role in regulating development of these tissues.
      The TBX20 gene maps to chromosome 7p14-p15. An association between TBX20 and loci
      for retinitis pigmentosa, RP9, and blepharophimosis syndrome, BPES, have been
      excluded.

PMID- 10936054
TI  - Cloning and chromosomal localization of a human class III myosin.
AB  - Two class III myosins have been identified to date: NINAC from Drosophila
      melanogaster and MyoIII(Lim) from Limulus polyphemus. Both have N-terminal kinase
      domains and are expressed exclusively in photoreceptors. Mutations in NINAC have
      been shown to alter the photoresponse and compromise photoreceptor survival. We
      report the cloning and chromosomal localization of a human class III myosin,
      MYO3A, from retina and a retinal pigment epithelial cell line. Human MYO3A (which
      we will refer to simply as MYO3A) possesses an N-terminal kinase domain and three
      consensus calmodulin-binding (IQ) motifs, two in the neck and one in the tail
      domain. We detected two MYO3A splice variants differing by 52 amino acids near
      the kinase/myosin junction. On Northern blots, MYO3A probes detected a 6. 5-kb
      transcript in human and monkey retina, in a cultured human RPE cell line (RPE
      19), and at much lower levels in human pancreas. A somatic hybrid panel PCR
      screen localized MYO3A to human chromosome 10, and a radiation hybrid screen
      further localized it proximal to marker D10S197, which is located at 10p11.1 on
      the human cytogenetic map. Since mutations in NINAC have been shown to alter the
      photoresponse and compromise photoreceptor survival, the human homologue MYO3A
      may also play a role in photoreceptor function and/or maintenance.

PMID- 10936055
TI  - ADAMTS9, a novel member of the ADAM-TS/ metallospondin gene family.
AB  - ADAM-TS/metallospondin genes encode a new family of proteins with structural
      homology to the ADAM metalloprotease-disintegrin family. However, unlike other
      ADAMs, these proteins contain thrombospondin type 1 (TSP1) repeats at the carboxy
      terminal end and are secreted proteins instead of being membrane bound. Members
      of the ADAM-TS family have been implicated in the cleavage of proteoglycans, the
      control of organ shape during development, and the inhibition of angiogenesis. We
      have cloned a new member of the ADAM-TS/metallospondin family designated here as
      ADAMTS9. This protein has a metalloprotease domain, a disintegrin-like domain,
      one internal TSP1 motif, and three carboxy-terminal TSP1-like submotifs. In
      contrast to other ADAM-TS family members, ADAMTS9 is expressed in all fetal
      tissues examined as well as some adult tissues. Using FISH and radiation hybrid
      analysis, we have localized ADAMTS9 to chromosome 3p14.2-p14.3, an area known to
      be lost in hereditary renal tumors.

PMID- 10936056
TI  - Cloning and characterization of human DDX24 and mouse Ddx24, two novel putative
      DEAD-Box proteins, and mapping DDX24 to human chromosome 14q32.
AB  - DEAD-box proteins are a large group of putative RNA helicases that exist
      ubiquitously in organisms ranging from bacteria to humans. They are likely to
      play important roles in many different RNA metabolic processes. In this paper, we
      report the cloning of human DDX24, a putative DEAD-box protein, and its ortholog,
      Ddx24 in mouse. The deduced proteins encoded by these two cDNAs share 78.7%
      identity at the amino acid level and possess all the well-conserved motifs of
      DEAD-box proteins. However, little homology can be found between them and other
      DEAD-box proteins, even in their core region (identity <40%). Northern blot
      analysis showed that a 3.0-kb transcript of human DDX24 exists ubiquitously in
      the 16 human tissues examined and was most abundant in heart and brain, but with
      lowest levels in thymus and small intestine. The mouse Ddx24, whose transcript is
      4.0 kb, was also expressed widely in 10 tissues tested with the highest level in
      heart and testis. By radiation hybrid mapping, the human DDX24 gene was localized
      to human chromosome 14q32 between the markers D14S81 and D14S265. Moreover, the
      gene structure of DDX24 was determined by comparing its cDNA and genomic sequence
      from BAC R-1089B7, which showed that the gene spanned a 30-kb region and
      consisted of at least nine exons.

PMID- 10936057
TI  - Introduction: interferon's connection to cancer.

PMID- 10936058
TI  - The interferon regulatory factors and oncogenesis.
AB  - We study a family of transcription factors, the interferon regulatory factors
      (IRFs), as originally identified in the context of the regulation of type-I
      interferon (IFN-alpha/beta) system. Most notably, studies on IRF-1 have revealed
      its remarkable functional diversity in the regulation of cellular responses of
      host defense, including oncogenesis. The IRF family has now expanded to nine
      members, and gene disruption studies have revealed critical involvement of some
      of the members in the regulation of cell growth and oncogenesis. In this review,
      we summarize our current knowledge on the involvement of members of the IRF
      family members, in particular, IRF-1, in oncogenesis.

PMID- 10936059
TI  - Role of the cytoplasmic domains of the type I interferon receptor subunits in
      signaling.
AB  - Type I interferons are imperative in maintaining a defense against viral
      infection. These cytokines also play an important role in the control of cell
      proliferation. These effects are triggered by ligand binding to a specific cell
      surface receptor. In the present article, we attempt to analyze the advances made
      in the last four years on type I interferon signaling. This review will focus on
      the contribution of the cytoplasmic domain of the alpha and betaL chains of the
      receptor to the activation of the Jak-Stat pathway. We also analyze the possible
      role of other pathways in interferon signaling.

PMID- 10936060
TI  - Novel functions of interferon-induced proteins.
AB  - Interferons are important cytokines which regulate antiviral, cell growth, immune
      modulatory and anti-tumor functions. These pleiotropic effects of interferons are
      brought about by a large number of cellular proteins, the interferon-inducible
      proteins. Investigation of the biochemical and cellular activities of some of
      these proteins have revealed new pathways of regulation of cellular RNA and
      protein metabolism, growth and differentiation, apoptosis and signal
      transduction. In this article we discuss recent findings on the novel activities
      of a selected number of interferon-induced proteins.

PMID- 10936061
TI  - The interferons and cell death: guardians of the cell or accomplices of
      apoptosis?
AB  - The interferons (IFNs) play an integral role in cellular host defense against
      virus infection and conceivably tumorigenesis. Despite over 50 years of research,
      however, the molecular mechanisms underlining IFN action remain to be fully
      elucidated, in part because of the large number of genes, with an uncharacterized
      function that appears to be induced by these cytokines. Although the majority of
      in vitro studies indicate that IFNs antiviral properties involve inhibiting viral
      replication while maintaining the integrity of the cell, numerous reports have
      now implicated that a number of IFN-induced genes, IFN transcriptional regulatory
      factors and IFN signaling molecules can also mediate apoptosis. Here, we review
      some of what is known about IFN's ability to invoke programmed cell death as part
      of an intricate arsenal intended to prevent viral infection and malignant
      disease.

PMID- 10936062
TI  - Immune-inflammatory mechanisms in IFNgamma-mediated anti-tumor activity.
AB  - IFNgamma is a functionally pleiotropic cytokine which shows considerable potency
      in promoting anti-tumor functions in vivo. Despite limited efficacy when
      delivered systemically either to experimental animals or patients, IFNgamma
      appears to play an important and perhaps critical role in directing the
      development of immune-mediated tumor destruction when expressed within the tumor
      bed. This has been demonstrated both by use of tumor cells transduced to express
      IFNgamma and by the use of IL-12 which is able, at least is murine models, to
      promote an IFNgamma-dependent, T cell mediated anti-tumor response. Recent
      studies indicate that the therapeutic efficacy of IFNgamma in tumor models
      depends critically upon the ability of the tumor cells themselves to respond to
      IFNgamma. Though IFNgamma is able to induce anti-viral activity and has direct
      anti-proliferative effects on some tumor cell lines, immunomodulatory function
      also appears to be an important component of its anti-tumor action. This is
      mediated through the action of several different classes of IFNgamma-inducible
      gene expression which control antigen processing and presentation, leukocyte
      trafficking, and indirect tumor cytotoxicity.

PMID- 10936063
TI  - Second-generation interferons for cancer: clinical targets.
AB  - IFNs were the first new therapeutic products resulting from recombinant DNA
      technology. IFNs were also the first human proteins effective in cancer
      treatment. There is however much to be discovered which will lead to new clinical
      applications. Areas which represent major research challenges for full
      understanding and application of the IFN system are: (i) the diversity of the IFN
      family; (ii) the role of induction; (iii) molecular mechanism of action; (iv)
      cellular modulatory effects; (v) advantages of combinations, and (vi)
      identification of new therapeutic indications. This review will emphasize the
      diversity of the IFN family and chemical modifications which will result in
      second-generation IFNs. Pre-clinical and clinical findings form the basis for new
      therapeutic directions in chronic myelogenous leukemia, lymphomas, myelomas,
      melanoma, urologic malignancies, primary brain tumors, and ovarian carcinoma.

PMID- 10936065
TI  - Introduction.

PMID- 10936064
TI  - Gene therapy of cancer with interferon: lessons from tumor models and
      perspectives for clinical applications.
AB  - Cytokine gene transfer is a current approach in studies of gene therapy of cancer
      IFNs represent valuable cytokines for these studies, since they exert multiple
      biological effects, including anti-tumor activities. Early studies have been
      focused on IFN-gamma. Recently, several reports have shown that the transfer of
      type I IFN (especially IFN-alpha) genes represents a powerful approach for
      inducing tumor suppression. Recent studies have underscored new IFN-induced
      activities on immune cells. This knowledge adds a further rationale for the use
      of IFN-alpha in strategies of gene therapy of cancer and can be exploited for the
      design of more selective and effective anticancer treatments.

PMID- 10936066
TI  - Hepatic polyploidy and liver growth control.
AB  - The onset of cellular polyploidy is recognized in all differentiated mammalian
      tissues. Polyploidy has been noted frequently in the normal liver, as well as in
      pathophysiological states of the liver. As insights into the significance of
      polyploidy accumulate gradually, it is becoming clear that cells belonging to
      high ploidy classes exhibit advancement toward terminal differentiation and
      cellular senescence with greater probabilities of apoptosis. Involvement of
      specific genetic abnormalities, such as impaired DNA repair, may lead to
      hepatocellular polyploidy. Working models indicate that extensive polyploidy
      could lead to organ failure, as well as to oncogenesis with activation of
      precancerous cell clones.

PMID- 10936067
TI  - Apoptosis and the liver.
AB  - Regulation of the homeostatic balance between cell proliferation and programmed
      cell death, apoptosis, is essential for development and maintenance of
      multicellular organisms. Apoptosis is a genetically and evolutionarily highly
      conserved process. Analysis of the molecular mechanisms of apoptosis has led to a
      better understanding of many human diseases. Notably in cancer, but also in
      infectious or autoimmune disease, a deficiency in apoptosis is one of the key
      events in pathophysiology. On the other hand, overefficient apoptosis, as
      observed in fulminant liver failure, may be equally harmful for the organism
      indicating that a tight regulation of the apoptotic machinery is essential for
      survival. The execution of apoptosis may be initiated by many different signals,
      either from within or outside the cell involving ligand-receptor interactions, as
      has been shown for Fas/Fas-ligand, TNF-alpha/TNF-receptor or TGF-beta/TGF
      receptor, or potentially by more unspecific signals such as ceramide or DNA
      damage. During the modulation phase of apoptosis many different genes such as
      p53, c-myc or Bcl-2/Bax have been shown to able to shift the balance either to
      cell survival or cell death.

PMID- 10936068
TI  - Genetics of hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the human cancers clearly linked to
      viral infections. Although the major viral and environmental risk factors for HCC
      development have been unravelled, the oncogenic pathways leading to malignant
      transformation of liver cells have long remained obscure. Recent outcomes have
      been provided by extensive allelotype studies which resulted in a comprehensive
      overview of the main genetic abnormalities in HCC, including DNA copy gains and
      losses. The differential involvement of the p53 tumor-suppressor gene in tumors
      associated with various risk factors has been largely clarified. Evidence for a
      crucial role of the reactivation of the Wnt/beta-catenin pathway, through
      mutations in the beta-catenin and axin genes in 30-40% of liver tumors,
      represents a major breakthrough. It has also been shown that the Rb pathway is
      frequently disrupted by methylation-dependent silencing of the p16INK4A gene and
      stimulation of Rb degradation by a proteosomal subunit. Presently, the
      identification of candidate oncogenes and tumor suppressors in the most
      frequently altered chromosomal regions is a major challenge. Great insights will
      come from integrating the signals from different pathways operating at
      preneoplastic and neoplastic stages. This search might, in time, permit an
      accurate evaluation of the major targets for therapeutic treatments.

PMID- 10936069
TI  - Impacts of chemicals on liver cancer risk.
AB  - Primary liver cancer (PLC) is of multifactorial etiology. Chronic infections by
      hepatitis B (HBV) and hepatitis C (HCV) viruses are major risk factors for most
      PLC cases worldwide, although mechanisms through which the infections cause PLC
      are still unknown. Epidemiologic and experimental evidence indicates that
      exposure to certain chemicals can also contribute significantly to PLC
      development, some of which have been designated as human liver carcinogens (Group
      1) by the International Agency for Research on Cancer. These include aflatoxins
      and chronic consumption of alcoholic beverages. Many naturally occurring and
      synthetic chemicals have been shown to induce liver cancer in experimental
      animals. Humans are exposed to these carcinogens via accidental contamination of
      food or water; usually at levels far lower than those that are carcinogenic to
      experimental animals. Consequently, assessment of possible human PLC risk
      associated with such exposures is complex and uncertain. Evidence regarding
      aflatoxin as a human carcinogen has been extensively documented and is reviewed
      as an example of the usefulness of parallel experimental and epidemiological
      investigations in cancer risk assessment. Aflatoxins are toxic metabolites of
      certain spoilage molds that are potent liver carcinogens in experimental animals
      and frequently contaminate human diets. Collectively, epidemiologic data together
      with evidence from many types of experimental models defines the role of
      aflatoxin exposure in PLC causation. Molecular epidemiology involving the use of
      biomarkers of exposure has been particularly effective in linking aflatoxin
      exposure to PLC. Biomarkers of aflatoxin exposure have been validated with
      particular thoroughness. Dose-response relationships between biomarker levels and
      liver tumor incidence were first established in experimental animals. The
      biomarkers were then employed in pilot studies of limited scale in humans to
      define sensitivity, specificity, accuracy, and reliability parameters. Further
      validation in transitional epidemiological studies assessed intra- and
      interindividual variability, background levels, external dose-marker
      relationship, and feasibility for use in larger population-based studies.
      Finally, prospective epidemiological studies were conducted to evaluate biomarker
      effectiveness in identifying PLC risk.

PMID- 10936070
TI  - Molecular bases for the development of hepatitis B virus (HBV)-related
      hepatocellular carcinoma (HCC).
AB  - Hepatocellular carcinoma (HCC) is the most common histological form of primary
      liver cancer; the tumor cells having retained features of hepatocytic
      differentiation. It is important to emphasize the heterogeneity of the
      histological background on which the tumor develops. Most HCCs complicate the
      evolution of an active or inactive cirrhosis. However, some tumors occur on
      livers with minimal histological changes; the prevalence of such cases varies
      from one geographical region to the other; being much higher in the southern half
      of Africa (around 40% of HCCs) than in Asia, America and Europe, where at least
      90% of HCCs are associated in the cirrhosis. This heterogeneity is probably a
      reflection of different environmental and genetic factors. A large number of
      epidemiological and molecular studies have indeed clearly demonstrated the prime
      importance of environmental factors to the development of primary liver cancers
      in humans. Chronic hepatitis B (HBV) and C (HCV) infections are major risk
      factors. This review will mainly analyse the impact of chronic HBV infection but
      it is important to emphasize the potential synergistic effects between HBV and
      HCV, as well as between viral infections and other environmental factors, such as
      alcohol, chemical carcinogens (see review by Dr Wogan) and other, still poorly
      defined, hormonal factors which may account for the higher incidence of the tumor
      in man. Finally the review by Dr Buendia highlights the emerging issue of liver
      cancer genetics.

PMID- 10936071
TI  - Hepatitis C virus and its pathogenesis.
AB  - Hepatitis C virus is a major causative agent of chronic hepatitis and the
      development of hepatocellular carcinoma. However, the roles of this virus in
      these diseases remain to be clarified, although it is likely that cytotoxic T
      lymphocytes (CTL) play crucial roles in the clearance of virus-infected cells,
      thus causing inflammation. In many, cases the clearance is not sufficient to
      eradicate all infected cells. This may be due to insufficient activation of CTL.
      In addition, it is also likely that the virus has some mechanism to escape from
      clearance. One such mechanism may be the suppression of apoptosis by activation
      of NF-kB or mitogenic function by virus proteins, and these functions may also be
      linked to the development of hepatocellular carcinoma.

PMID- 10936072
TI  - Circulating tumorous cells in patients with hepatocellular carcinoma. Clinical
      impact and future directions.
AB  - The circulation of liver-derived cells in patients with hepatocellular carcinoma
      (HCC) has been demonstrated by reverse transcriptase-polymerase chain reaction
      (RT-PCR) analyses. Contrasting results have been reported until now about the
      clinical impact of these assays, mainly due to technical differences. The use of
      RT-PCR approaches is now clearly, not suitable for recognition of circulating
      tumorous cells (CTC) when the test is performed after invasive medical or
      surgical procedures. Furthermore, the RT-PCR approach is incapable of analyzing
      the expression of invasion-related genes in CTC. Recently, new assays have been
      proposed to isolate CTC. They allow immunomorphological and molecular
      characterization of individual tumor cells. Based on these new results, new
      therapeutic approaches of metastases should be developed in the near future.

PMID- 10936073
TI  - Methylmercury affects multiple subtypes of calcium channels in rat cerebellar
      granule cells.
AB  - We tested the ability of methylmercury (MeHg) to block calcium channel current in
      cultures of neonatal cerebellar granule cells using whole-cell patch clamp
      techniques and Ba(2+) as charge carrier. Low micromolar concentrations of MeHg
      (0.25-1 microM) reduced the amplitude of whole cell Ba(2+) current in a
      concentration- and time-dependent fashion; however, this effect was not voltage
      dependent and the current-voltage relationship was not altered. Increasing the
      stimulation frequency hastened the onset and increased the magnitude of block at
      both 0.25 and 0.5 microM MeHg but not at 1 microM. In the absence of stimulation,
      all concentrations of MeHg were able to decrease current amplitude. The ability
      of several Ca(2+) channel antagonists (omega-conotoxin GVIA, omega-conotoxin
      MVIIC, omega-agatoxin IVA, calcicludine, and nimodipine) to alter the MeHg
      induced effect was tested in an effort to determine if MeHg targets a specific
      subtype of Ca(2+) channel. Each of the antagonists tested was able to decrease a
      portion of whole cell Ba(2+) current under control conditions. However, none were
      able to attenuate the MeHg-induced block of whole cell Ba(2+) current, suggesting
      either that the mechanism of MeHg-induced block involves sites other than those
      influenced specifically by Ca(2+) channel antagonists or that MeHg was able to
      "outcompete" these toxins for their binding sites. These results show that acute
      exposure to submicromolar concentrations of MeHg can block Ba(2+) currents
      carried through multiple Ca(2+) channel subtypes in primary cultures of
      cerebellar granule cells. However, it is unlikely that the presence of a specific
      Ca(2+) channel subtype is able to render granule cells more susceptible to the
      neurotoxicologic actions of MeHg.

PMID- 10936074
TI  - Enhancing effects of 2-amino-4,5-diphenylthiazole-induced polycystic kidneys on
      renal carcinogenesis in rats treated with dimethylnitrosamine.
AB  - The effects of the polycystic kidney environment on dimethylnitrosamine (DMN)
      induced renal carcinogenesis were investigated in rats. In Experiment 1, male
      Wistar rats were given 25 or 10 ppm DMN in their drinking water and
      simultaneously administered 1% 2-amino-4,5-diphenylthiazole (DPT) in the diet for
      30 weeks. DPT-induced polycystic kidney was associated with a significant
      increase in the number of renal cell tumors and incidence of mesenchymal tumors
      in the 25 ppm DMN + DPT group and the incidence of atypical tubules in the 10 ppm
      DMN + DPT group. PCNA labeling indices of cystic renal tubules in DPT-treated
      rats were significantly higher than for corresponding noncystic tubules. In
      Experiment 2, PCNA indices of renal tubules in 10 ppm + DPT rats and
      immunohistochemically CYP2E1-positive renal tubules in DPT-treated rats were
      demonstrated to be significantly increased on day 14. CYP2E1 mRNA expression in
      the kidneys of DPT-treated rats showed a fivefold increase over constitutive
      levels. The results thus indicate that DPT induction of polycystic kidneys
      enhances DMN-induced renal carcinogenesis in rats, with DPT-induced elevated cell
      proliferation and CYP2E1 expression in renal tubules as possible underlying
      mechanisms.

PMID- 10936075
TI  - Low-level toluene disrupts auditory function in guinea pigs.
AB  - Toluene appears to have adverse effects on the human auditory system, but it is
      difficult to estimate its potency since it is commonly present in the workplace
      in combination with noise exposure; workplace noise exposures are often highly
      variable. Studies designed to assess toluene ototoxicity specifically have been
      limited to high-dose studies in a single laboratory animal model, the rat. Here
      permanent hearing loss has been observed at concentrations of 1000 ppm toluene
      and greater after inhalation exposure for 5 days, 6 h/day. The OSHA threshold
      limit value for toluene is only 100 ppm. The current study focuses on the onset
      of toluene ototoxicity acutely in the guinea pig and in adducing a mechanism of
      effect. In this study, evidence is presented for the impairment of auditory
      function by toluene in the guinea pig, at a concentration substantially lower
      than that used for studying permanent impairment in the rat. The impaired
      function was correlated with reduced energy metabolism in outer hair cells.
      Assessment of auditory function was made using distortion product otoacoustic
      emissions (DPOAE) with subsequent measurement of succinate dehydrogenase (SDH)
      staining density in hair cells using surface preparations. Temporary disruption
      of auditory function in guinea pigs is seen in subjects exposed to 250, 500, and
      1000 ppm toluene for 8 h/day, 5 day/week for 1 and 4 weeks. Concentrations as low
      as 250 ppm toluene were able to disrupt auditory function acutely in the guinea
      pig, and 500 and 1000 ppm toluene produced greater acute dysfunction. SDH
      staining suggests that reduced enzyme activity in the midfrequency region of the
      cochlea occurs acutely following toluene exposure. Although the auditory
      dysfunction progressed between 1 and 4 weeks of exposure, a permanent loss did
      not develop for these subjects and hair cell death was not seen. The current
      study identifies early evidence of auditory system impairment in the guinea pig
      at low toluene concentration and evidence for impairment of energy production in
      hair cells. While even a transient auditory impairment has implications for
      workplace safety, additional study on the transition from such acute effects to
      permanent impairment is essential.

PMID- 10936076
TI  - The role of oxygen and reduced oxygen species in nitric oxide-mediated
      cytotoxicity: studies in the yeast Saccharomyces cerevisiae model system.
AB  - The cytotoxicity of nitric oxide (NO) is well established, yet the mechanism(s)
      of its cytotoxicity is (are) still undefined and a matter of significant interest
      and speculation. Many of the previously proposed mechanisms for NO-mediated
      cytotoxicity involve interactions between NO and molecular oxygen (O(2)) and/or
      O(2)-derived species such as O(-)(2) and H(2)O(2). The yeast Saccharomyces
      cerevisiae represents a useful model system for evaluating the role of O(2) and
      O(2)-derived species in NO-mediated cytotoxicity. This study examines the
      contribution of O(2) and O(2)-derived species to NO-mediated cytotoxicity in the
      yeast S. cerevisiae. NO-mediated cytotoxicity was determined to be O(2)
      dependent. However, this O(2) dependence was only minimally due to the generation
      of O(2)-derived species such as O(-)(2) and/or H(2)O(2).

PMID- 10936077
TI  - Ascorbic acid promotes recovery of cellular functions following toxicant-induced
      injury.
AB  - We have shown that renal proximal tubular cells (RPTC) recover cellular functions
      following sublethal injury induced by the oxidant t-butylhydroperoxide but not by
      the nephrotoxic cysteine conjugate dichlorovinyl-L-cysteine (DCVC). This study
      investigated whether L-ascorbic acid phosphate (AscP) promotes recovery of RPTC
      functions following DCVC-induced injury. DCVC exposure (200 microM; 100 min)
      resulted in 60% RPTC death and loss from the monolayer at 24 h independent of
      physiological (50 microM) or pharmacological (500 microM) AscP concentrations.
      Likewise, the DCVC-induced decrease in mitochondrial function (54%), active Na(+)
      transport (66%), and Na(+)-K(+)-ATPase activity (77%) was independent of the AscP
      concentration. Analysis of Na(+)-K(+)-ATPase protein expression and distribution
      in the plasma membrane using immunocytochemistry and confocal laser scanning
      microscopy revealed the loss of Na(+)-K(+)-ATPase protein from the basolateral
      membrane of RPTC treated with DCVC. DCVC-injured RPTC cultured in the presence of
      50 microM AscP did not proliferate nor recover their physiological functions over
      time. In contrast, RPTC cultured in the presence of 500 microM AscP proliferated,
      recovered all examined physiological functions, and the basolateral membrane
      expression of Na(+)-K(+)-ATPase by day 4 following DCVC injury. These results
      demonstrate that pharmacological concentrations of AscP do not prevent toxicant
      induced cell injury and death but promote complete recovery of mitochondrial
      function, active Na(+) transport, and proliferation following toxicant-induced
      injury.

PMID- 10936078
TI  - Metabolic activation of the proestrogens trans-stilbene and trans-stilbene oxide
      by rat liver microsomes.
AB  - A liver microsome-mediated activation of the proestrogens trans-stilbene and
      trans-stilbene oxide was found in this study. trans-Stilbene and trans-stilbene
      oxide were negative in estrogen reporter assay using estrogen-responsive human
      breast cancer cell line MCF-7 and growth assay in rat pituitary tumor cell line
      MtT/E-2. However, these compounds exhibited estrogenic activity after incubation
      with liver microsomes of 3-methylcholanthrene-treated rats in the presence of
      NADPH. In contrast, cis-stilbene and cis-stilbene oxide did not show estrogenic
      activity after such incubation. When trans-stilbene was incubated with the liver
      microsomes of 3-methylcholanthrene-treated rats in the presence of NADPH, two
      metabolites were detected by HPLC. They were identified unequivocally as trans-4
      hydroxystilbene and trans-4, 4'-dihydroxystilbene by mass and UV spectral
      comparison with authentic samples. The oxidase activity of the liver microsomes
      toward trans-stilbene was inhibited by SKF 525-A and alpha -naphthoflavone. Minor
      activity was observed when liver microsomes of untreated or phenobarbital-treated
      rats were used instead of those from 3-methylcholanthrene-treated rats. trans-4
      Hydroxystilbene and trans-4,4'-dihydroxystilbene exhibited significant estrogenic
      activities. These results suggest that the estrogenic activities of trans
      stilbene and trans-stilbene oxide were due to formation of hydroxylated
      metabolites.

PMID- 10936079
TI  - Cytotoxicity and biotransformation of the anticancer drug perillyl alcohol in
      PC12 cells and in the rat.
AB  - The cytotoxic monoterpene perillyl alcohol (POH) has anticancer properties. We
      investigated its cytotoxicity in PC12 cells in relation to its biotransformation.
      POH is oxidized by alcohol dehydrogenase and aldehyde dehydrogenase to
      perillaldehyde (PCO) and perillic acid (PCOOH), respectively. Apoptosis was
      determined by cell cycle (subG(0)G(1)) analysis and AnnexinV staining followed by
      flow cytometry. PCO caused apoptosis at 200 microM, POH caused apoptosis from 500
      microM on, while PCOOH had no effect. The caspase inhibitor zVAD prevented
      apoptosis. Inhibition of POH oxidation by 4-methylpyrazol did not prevent the
      apoptotic effect of POH indicating that POH itself is also apoptotic. To find out
      to what extent POH is metabolized to PCO, the metabolism of POH, PCO, and PCOOH
      was determined after intravenous injection in the rat and in isolated
      hepatocytes. Although PCO can form a glutathione conjugate(s), no indication of
      the formation of GSH conjugates was found either in vivo or in hepatocytes. About
      70% of the dose was recovered as glucuronides in bile and urine. PCOOH generated
      only the acyl glucuronide, while POH and PCO formed both acyl and ether
      glucuronides. These results indicate that PCO is a major intermediary metabolite
      of POH in the rat in vivo and suggest that PCO may contribute to the anticancer
      effect of POH.

PMID- 10936080
TI  - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on initiation and promotion of GST
      P-positive foci in rat liver: A quantitative analysis of experimental data using
      a stochastic model.
AB  - We use a stochastic model describing initiation and clonal growth of altered
      cells to analyze data from an initiation-promotion hepatocarcinogenesis
      experiment in female Wistar rats. Starting at 7 weeks of age, the animals were
      treated for 10 days with the initiating agent diethylnitrosamine (DEN, 10 mg/kg
      body wt per day). After a 10-week resting period, the animals were treated either
      with corn oil or with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) via biweekly sc
      injections of 1.4 microg/kg body wt of TCDD dissolved in corn oil. Groups of four
      or five animals were euthanized 3, 17, 31, 73, and 115 days after start of
      TCDD/corn oil treatment. The data analyzed consist of the number and sizes of GST
      P-positive focal transections at various time points. By fitting the model to the
      data, we estimate the rates of initiation, cell division, and cell death during
      different time periods of the experiment. The model estimates of cell kinetic
      parameters are consistent with directly made experimental observations of cell
      division and cell death. The model predicts that DEN-induced initiation of GST-P
      positive cells is highly protracted in controls and TCDD-treated animals alike.
      We also find that TCDD interferes with the normal rate at which cells with (DEN
      inflicted) DNA damage are converted into cells expressing the GST-P-positive
      phenotype, suggesting a TCDD-mediated "acceleration" of the appearance of de novo
      GST-P-positive initiated cells from damaged precursor cells. Furthermore, the
      model predicts a significant reduction in the rate of apoptosis within the first
      4 to 5 weeks of TCDD treatment, and after 10 weeks of TCDD treatment, but not in
      between.

PMID- 10936081
TI  - Cell receptors involved in adenovirus entry.

PMID- 10936082
TI  - CD46 as a measles receptor: form follows function.

PMID- 10936083
TI  - Corf, the Rev/Rex homologue of HTDV/HERV-K, encodes an arginine-rich nuclear
      localization signal that exerts a trans-dominant phenotype when mutated.
AB  - Regulation of nucleo-cytoplasmic export of viral transcripts by a viral protein
      (Rev/Rex) is a characteristic feature in the replication cycle of complex
      retroviruses. We recently reported that the endogenous retrovirus family
      HTDV/HERV-K encodes a protein, Corf, that is a cellular Counterpart of Rev/Rex
      function and thus a new component of nucleo-cytoplasmic pathways. In HTDV/HERV-K
      expressing cells, Corf is localized within the nucleoli. Here we describe the
      nuclear localization signal (NLS) of the Corf protein. Mutations in the NLS lead
      to cytoplasmic accumulation of the mutated protein and abrogate Corf function in
      a trans-dominant way.

PMID- 10936085
TI  - Chimeric Langat/Dengue viruses protect mice from heterologous challenge with the
      highly virulent strains of tick-borne encephalitis virus.
AB  - Langat virus (LGT), a tick-borne flavivirus, is naturally attenuated for humans
      but it is very virulent in SCID mice. In contrast, viable recombinant chimeras of
      LGT (preM and E genes) and dengue type 4 virus (all other sequences) recovered in
      mosquito cell culture were completely attenuated in SCID mice but still capable
      of providing protection against LGT. To develop the chimeras into vaccine
      candidates, we adapted them to replicate efficiently in simian Vero cells, a
      satisfactory substrate for human vaccines. The adapted chimeras remained
      completely attenuated for SCID mice and, significantly, provided protection in
      immunocompetent mice against tick-borne encephalitis virus, the most virulent of
      the tick-borne flaviviruses.

PMID- 10936084
TI  - Selective inhibition of nuclear steroid receptor function by a protein from a
      human tumorigenic poxvirus.
AB  - The poxvirus molluscum contagiosum (MC) has a worldwide distribution and its
      prevalence is on the rise. Here we report that the MCV MC013L protein inhibits
      glucocorticoid and vitamin D, but not retinoid or estrogen, nuclear receptor
      transactivation. A direct interaction of MC013L with glucocorticoid and vitamin D
      receptor is supported by yeast two-hybrid, GST pull-down, and far Western blot
      analyses. Glucocorticoids act as potent inhibitors of keratinocyte proliferation,
      while vitamin D and retinoids promote and block terminal differentiation,
      respectively. Therefore, MC013L may promote efficient virus replication by
      blocking the differentiation of infected keratinocytes. MC013L may be the first
      member of a new class of poxvirus proteins that directly modulate nuclear
      receptor-mediated transcription.

PMID- 10936086
TI  - Intracellular and intercellular movement of maize streak geminivirus V1 and V2
      proteins transiently expressed as green fluorescent protein fusions.
AB  - Transient expression of the maize streak geminivirus virion-sense proteins V1 and
      V2 (movement protein, MP, and coat protein, CP, respectively) in maize leaves
      allowed investigation of their roles in inter- and intracellular movement.
      Bombardment of a construct directing expression of a V1:green fluorescent protein
      (GFP) fusion product resulted in significantly increased spread of fluorescence
      from the bombarded cell to adjacent cells compared to that obtained following
      expression of free GFP. A mutant V1:GFP fusion product exhibited markedly less
      movement than the V1:GFP protein. Thus, the MSV V1 protein moves from cell to
      cell in the absence of other viral proteins. However, V1:GFP did not localize to
      plasmodesmata in maize or tobacco leaves although a tobacco mosaic virus MP:GFP
      fusion protein was shown to do so in tobacco. The CP:GFP fusion product targeted
      exclusively to the nucleus and did not move from cell to cell or exit the nucleus
      when expressed alone. When coexpressed with V1, some CP:GFP fluorescence was seen
      at the cell periphery in a proportion of cells, but in no case was cell-to-cell
      movement of CP:GFP detected. The likely roles of V1 and CP in MSV movement are
      discussed.

PMID- 10936088
TI  - T-Cell reactivity to the P2C nonstructural protein of a diabetogenic strain of
      coxsackievirus B4.
AB  - Enteroviruses are proposed as initiating factors in the etiology of Type 1
      diabetes mellitus (Type 1 DM). Molecular mimicry between the autoantigen glutamic
      acid decarboxylase 65 (GAD65) and the coxsackievirus B4 (CVB4) nonstructural
      protein P2C is frequently cited as a mechanism by which this virus triggers the
      disease, but little is known about the immunogenicity of this viral protein in
      humans, mainly due to the problem of obtaining highly pure preparations of P2C.
      We generated large amounts of highly pure, soluble P2C protein, coupled to the
      fusion partner maltose binding protein (MBP-P2C) using the PMAL-c2 bacterial
      expression plasmid and a two-step purification system comprising amylose resin
      and ion exchange. Using purified viral protein we show that specific T-cell
      responses against P2C are detected in the blood of healthy donors and Type 1 DM
      patients. Proliferation responses to P2C were detected only in subjects also
      demonstrating T-cell proliferation to CVB4 Vero cell lysates. However, in
      additional cases T-cell responses to P2C were detectable through the release of
      interferon-gamma or interleukin-4 in individuals who did not make proliferative
      responses. Taken together, our data show that the P2C nonstructural protein of
      CVB4 is targeted by T cells during the antiviral immune response and may trigger
      the production of T helper 1 and T helper 2 cytokines. The availability of pure,
      immunogenic P2C should allow the putative role of antiviral responses in the
      development of autoimmune diabetes to be investigated.

PMID- 10936087
TI  - Disruption of PML-associated nuclear bodies by IE1 correlates with efficient
      early stages of viral gene expression and DNA replication in human
      cytomegalovirus infection.
AB  - In human cytomegalovirus (HCMV) infection, both of the major immediate-early
      proteins IE1(IE68, UL123) and IE2(IE86, UL122) target to PML protein-associated
      nuclear bodies known as PODs or ND10 at very early times after infection. IE1
      causes a redistribution of both PML and IE1 from the PODs into a nuclear diffuse
      form, whereas IE2 initially localizes adjacent to PODs but later associates with
      viral DNA replication compartments. The peripheries of PODs are also believed to
      be sites for initiation of both viral IE transcription and DNA replication.
      However, because IE1 is nonessential at high multiplicity of infection (m.o.i.)
      in HF cells, the exact role of these processes in viral infection has been
      enigmatic. Therefore, we investigated the effects of overexpression of PML in the
      presence or absence of IE1 on the intranuclear distribution of IE2 and formation
      of viral DNA replication compartments, as well as on the levels of delayed-early
      and late viral transcription and protein accumulation. Infection with wild-type
      HCMV(Towne) and the IE1-deleted derivative HCMV(CR208), which fails to disrupt
      PODs, was compared in a pair of related astrocytoma/glioblastoma cell lines, the
      U373-Neo control and a variant U373-PML that constitutively overexpresses
      PML(560) in much larger than normal PODs. IFA studies on the localization
      patterns for IE1, IE2, and PML showed that, although the numbers of IE2-positive
      cells were not significantly reduced in either the wild-type virus-infected U373
      PML cell line or in DeltaIE1-infected control cells, POD disruption by IE1 in
      wild-type virus infection was delayed by up to 6 h in U373-PML cells compared to
      control cells. Furthermore, there was considerable enhancement of IE2
      colocalization with PODs in Delta IE1-infected U373-PML cells. Formation of viral
      DNA replication compartments in the U373-PML cell line was also greatly delayed,
      measured at fivefold lower after wild-type virus infection and 12-fold lower
      after infection with Delta IE1 than in the control cell line at 48 h at an m.o.i.
      of 1.0. The levels of representative early and late viral proteins detected by
      Western blotting were suppressed by fivefold and 22-fold at 24 and 72 h,
      respectively, in the U373-PML cell line, even with high m. o.i. wild-type HCMV
      infection. Decreased viral protein levels also occurred when control cells were
      infected with the Delta IE1 virus and these two effects were additive in the U373
      PML cell line. Similarly, when U373-PML cells were infected with recombinant HCMV
      expressing an extragenic luciferase reporter gene under the control of viral
      early (Pol) or late (pp28) promoters, their transcriptional activation was
      reduced up to fivefold at both high and low m.o.i. compared to that of the
      control cells. Overall, these results suggest that POD disruption by IE1 and
      subsequent redistribution of both PML and IE1 at very early times after infection
      may play an important role in the efficient utilization of cellular transcription
      and replication machinery by HCMV and contribute to rapid progression of the HCMV
      lytic cycle.

PMID- 10936089
TI  - Identification of a novel p53 mutation in JCV-induced mouse medulloblastoma.
AB  - Medulloblastoma, a malignant invasive tumor of the cerebellum, is one of the most
      common neoplasms of the nervous system in children. Utilization of the human
      neurotropic virus JC virus (JCV) early gene T-antigen allowed the development of
      a transgenic animal that models human medulloblastoma. Here we describe the
      characterization of two distinct populations of cells derived from the JCV
      induced mouse medulloblastoma. Results from immunohistochemical and biochemical
      studies revealed the expression of T-antigen in some but not all tumor cells. In
      T-antigen-producing cells, T-antigen was found in association with wild-type p53
      and pRb, two tumor suppressors that control cell growth and differentiation. In
      cells that lack expression of T-antigen, a novel mutant p53 with a deletion
      between residues 35 and 123 was detected. Morphological differences were observed
      between the two populations of cells, though there was no significant difference
      in their growth rates. However, subcutaneous transplantation of the T-antigen
      positive, but not T-antigen-negative, cells resulted in the development of
      massive tumors in experimental animals. In light of earlier reports on the
      association of JCV with human medulloblastoma, the mouse cell lines described in
      this study may provide a valuable tool for deciphering the pathways involved in
      the formation and progression of medulloblastoma.

PMID- 10936090
TI  - Characterization of modified hepatitis C virus E2 proteins expressed on the cell
      surface.
AB  - The envelope proteins of hepatitis C virus (HCV) are the likely targets of
      neutralizing antibodies and their molecular and functional characterization is
      relevant for vaccine development. We previously showed that surface-expressed E2
      is a better immunogen than intracellular E2 and, therefore, we were interested in
      exploring more efficient ways to present E2 protein on the cell surface. We found
      that E2 targeted to the cell surface by replacement of its transmembrane domain
      did not bring E1 to the surface although E1 could be expressed independently on
      the cell surface if its transmembrane domain was similarly replaced. FACS
      analysis suggested that E2 expressed on the cell surface acquired its native
      conformation more efficiently when truncated at aa 661 than when truncated at aa
      715. The shorter form of truncated E2 better retained the ability to bind the
      second extracellular loop (EC2) of CD81, the putative HCV receptor.
      Interestingly, deletion of the hypervariable region 1 (HVR1) did not perceptibly
      alter E2 structure; cell-surface forms of E2 lacking the HVR1 remained reactive
      with conformation-sensitive MAbs and were able to bind recombinant EC2 of CD81.

PMID- 10936091
TI  - The HTLV-I orfI protein is recognized by serum antibodies from naturally infected
      humans and experimentally infected rabbits.
AB  - The mechanism of T-cell transformation by human T-cell lymphotropic virus type I
      (HTLV-I), though not completely understood, appears to involve the interactions
      of several viral and cellular proteins. One of these viral proteins, p12(I),
      encoded by HTLV-I orfI, is a weak oncogene that binds the 16-kDa subunit of the
      vacuolar ATPase and interacts with the immature beta and gamma(c) chains of the
      IL-2 receptor. We have expressed the singly spliced orfI cDNA in the baculovirus
      system and used the recombinant protein as a tool to assess the presence of
      antibodies in naturally or experimentally infected hosts. In addition, rabbit
      antisera were raised against various p12(I) synthetic peptides and used to
      identify three antigenic regions within p12(I), one between the two putative
      transmembrane regions of p12(I) and two at the carboxy-terminus of the protein.
      More importantly, sera from a naturally infected human (1 of 32) and
      experimentally infected rabbits (9 of 20) recognized the rp12(I), demonstrating
      orfI expression and immunogenicity in vivo. Taken together these data provide the
      first evidence of orfI expression during HTLV-I infections.

PMID- 10936092
TI  - Defining CTL-induced pathology: implications for HIV.
AB  - The relationship between virus and host cells is multifactorial and nonlinear.
      This indicates that the effect of an immune response on infection can lead to
      several different outcomes. These include severe immunopathology. We seek to
      define properties of CTL-induced pathology in viral infections and examine the
      implications for HIV disease progression. We find that CTL-induced pathology is
      observed if the rate of viral replication is fast relative to the CTL
      responsiveness of the host. Theoretical predictions are consistent with empirical
      data on LCMV infection. These conditions are also sufficient to induce pathology
      in HIV infection. However, the absence of HIV-specific CTL can result in an
      equivalent depletion of the CD4 T cell pool as a consequence of the short life
      span of activated T cells. A mathematical model describing the evolution of HIV
      coreceptor usage in the context of lytic and nonlytic CD8 cell responses might
      account for the relatively long time span required to result in disease. Viral
      evolution toward parameter ranges allowing CTL-induced pathology is difficult to
      achieve. It requires the emergence of fast viral replication together with escape
      from nonlytic CTL responses. However, according to the model, fast viral
      replication can result in the evolution of virus strains that are susceptible to
      chemokine-mediated inhibition of viral replication.

PMID- 10936093
TI  - Molecular and biological interactions between two HIV-1 strains from a coinfected
      patient reveal the first evidence in favor of viral synergism.
AB  - An intravenous drug user was found to be dually infected with two genetically and
      phylogenetically distinct human immunodeficiency virus type 1 (HIV-1) subtype B
      strains (designated groups I and II). Viral isolation revealed a simultaneous
      copassaging of two strains in PBMC. The culture of viral strains on monocytes and
      monocyte-derived macrophages preferentially segregated the two viral strains. The
      group I strain utilized CXCR4 and group II used CCR5 coreceptor for entry.
      Sequencing of >100 clones from uncultured PBMC consistently showed the
      predominance of group II virus in vivo. Importantly, the group II virus alone
      could not productively infect PBMC, but when used together with group I virus for
      infection, the group II virus regained its high replication potential and
      predominance in cultured PBMC. These data are the first to provide direct
      evidence in favor of molecular and biological interaction between two infecting
      strains in a coinfected patient and show their differential pathogenic effects,
      tropism, and modes of entry. In addition, our data provide the first evidence for
      synergism between these two strains. Cumulatively, these data emphasize that in
      order to clearly interpret coreceptor usage, biological segregation of viral
      strains from primary isolates in vitro may be imperative.

PMID- 10936094
TI  - Complete genomic sequence of the Amsacta moorei entomopoxvirus: analysis and
      comparison with other poxviruses.
AB  - The genome of the genus B entomopoxvirus from Amsacta moorei (AmEPV) was
      sequenced and found to contain 232,392 bases with 279 unique open reading frames
      (ORFs) of greater than 60 amino acids. The central core of the viral chromosome
      is flanked by 9.4-kb inverted terminal repeats (ITRs), each of which contains 13
      ORFs, raising the total number of ORFs within the viral chromosome to 292. ORFs
      with no known homology to other poxvirus genes were shown to constitute 33.6% of
      the viral genome. Approximately 28.6% of the AmEPV genome encodes homologs of the
      mammalian poxvirus colinear core genes, which are found dispersed throughout the
      AmEPV chromosome. There is also no significant gene order conservation between
      AmEPV and the orthopteran genus B poxvirus of Melanoplus sanguinipes (MsEPV).
      Novel AmEPV genes include those encoding a putative ABC transporter and a Kunitz
      motif protease inhibitor. The most unusual feature of the AmEPV genome relates to
      the viral encoded poly(A) polymerase. In all other poxviruses this heterodimeric
      enzyme consists of a single large and a single small subunit. However, AmEPV
      appears to encode one large and two distinct small poly(A) polymerase subunits.
      AmEPV is one of the few entomopoxviruses which can be grown and manipulated in
      cell culture. The complete genomic sequence of AmEPV paves the way for an
      understanding and comparison of the molecular properties and pathogenesis between
      the entomopoxviruses of insects and the more intensively studied vertebrate
      poxviruses.

PMID- 10936095
TI  - Production of functionally deficient dendritic cells from HTLV-I-infected
      monocytes: implications for the dendritic cell defect in adult T cell leukemia.
AB  - Adult T cell leukemia (ATL) is induced by an infection with human T lymphotropic
      virus type I (HTLV-I) and is accompanied by immunodeficiency. Monocyte-derived
      immature dendritic cells (DCs) donated by 11 ATL patients were suppressed in the
      ability to take up fluorescein isothiocyanate (FITC)-dextran and were down
      regulated in the expression of CD1a and CD86 antigens (Ags). Monocytes from the
      patients showed impaired expression of CD14 and HLA-DR Ags. These results suggest
      intrinsic abnormalities of monocytes and a defect of DC maturation in ATL
      patients. Therefore, we examined the influence of HTLV-I infection of monocytes
      on their differentiation to DCs. Monocytes obtained from healthy donors were
      susceptible to HTLV-I infection in vitro. HTLV-I-infected monocytes were down
      regulated in the expression of CD14 Ags, and immature DCs obtained from them
      expressed CD1a poorly and were impaired in the ability to take up FITC-dextran.
      Mature DCs differentiated from these cells could not stimulate autologous CD4(+)
      T cell or CD8(+) T cell proliferation, even after being secondarily pulsed with
      HTLV-I at an immature DC stage. These results suggest that HTLV-I-infected
      monocytes cannot properly differentiate to DCs and that this might be one of the
      important mechanisms producing dysfunctional DCs in ATL patients.

PMID- 10936096
TI  - Evaluation of immune responses induced by HIV-1 gp120 in rhesus macaques: effect
      of vaccination on challenge with pathogenic strains of homologous and
      heterologous simian human immunodeficiency viruses.
AB  - The simian human immunodeficiency virus (SHIV) macaque model of AIDS has provided
      a very useful system for evaluation of envelope-based candidate vaccines against
      HIV-1. Eight rhesus macaques were immunized with monomeric recombinant gp120 of
      HIV-1(LAI) (rgp120) and used to evaluate whether this vaccine conferred
      protection against challenge with pathogenic SHIVs (SHIV(KU-2) and SHIV(89.6)P).
      The vaccinated macaques developed high titers of antibodies against rgp120 that
      reacted efficiently with the envelope proteins of homologous SHIV (SHIV(KU-2))
      and poorly with the SHIV(89.6)P envelope, a heterologous strain of SHIV. This
      vaccine also induced neutralizing antibodies but only against SHIV(KU-2). Vaccine
      induced antibodies were of high avidity and predominantly against linear epitopes
      on the protein. Vaccinated macaques developed gp120-specific T-helper cells but
      no consistent cytotoxic T lymphocytes. However, cellular immune responses were
      short-lived in all eight vaccinates. At week 22 postimmunization, four vaccinates
      were challenged with SHIV(KU-2) and the other four with SHIV(89.6)P. Four
      unvaccinated control macaques were also infected: two with SHIV(KU-2) and two
      with SHIV(89.6)P. Vaccinated macaques generally showed anamnestic antibody and T
      helper cell responses. However, T-helper responses were again short-lived. Upon
      challenge, the level of productive virus replication was indistinguishable
      between vaccine and control groups, suggesting that rgp120 did not confer
      protection against virus replication when animals were challenged with homologous
      or heterologous SHIV viruses.

PMID- 10936097
TI  - Purified JC virus T and T' proteins differentially interact with the
      retinoblastoma family of tumor suppressor proteins.
AB  - The amino termini of polyomavirus T antigens contain LXCXE and J domains, which
      are necessary for binding and inactivating the retinoblastoma family of tumor
      suppressors. Both of these motifs are found in the JC virus (JCV) early proteins
      T'(135), T'(136), and T'(165), leading to the suggestion that these recently
      discovered proteins complement the cell-cycle-deregulating function of the JCV
      large T antigen (TAg). To investigate this hypothesis, the three JCV T' proteins
      were produced in a baculovirus expression system and purified by immunoaffinity
      chromatography. To facilitate purification, hybridomas that secrete antibodies
      recognizing amino-terminal epitopes of JCV early proteins were produced.
      Potential interactions between the early viral proteins and the cellular proteins
      pRB, p107, and p130 were investigated by incubating purified JCV TAg and T'
      proteins with extracts of MOLT-4 cells, a human T cell line. The four viral
      proteins preferentially bound hypophosphorylated species of the cellular proteins
      and exhibited the highest binding affinity to p107 and the lowest affinity to
      pRB. TAg and T'(165) bound more pRB and less p107 than did T'(135) and T'(136);
      T'(165) also bound less p130 than the other three early proteins. Results of
      these in vitro interactions were compared to those obtained in vivo using POJ
      cells, a transformed human glial cell line that expresses JCV early proteins,
      relatively high levels of pRB and p107, and low levels of p130. Most of the pRB
      in POJ cells is hyperphosphorylated, and only a fraction of the
      hypophosphorylated form(s) of pRB is bound by the viral proteins. In contrast,
      only hypophosphorylated p130 is detected in the transformed cells, and most of
      this protein was found in complex with the viral proteins. Finally, nearly all of
      the p107 in POJ cells is bound by the JCV proteins.

PMID- 10936098
TI  - Virus-specific adaptations for the production of a pseudorecombinant virus formed
      by two distinct bipartite geminiviruses from Central America.
AB  - Most whitefly-transmitted geminiviruses possess bipartite genomes comprising DNAs
      A and B. The production of viable pseudorecombinants by reassortment of
      infectious cloned components is generally limited to isolates/strains of a
      particular virus. Following exchange of cloned genomic components of Sida golden
      mosaic virus from Costa Rica (SiGMV/Co) and Sida golden mosaic virus from
      Honduras (SiGMV/Ho(yv)), the pseudorecombinant viruses were infectious in various
      plant species. Three DNA B components (B(1), B(2), B(3)), different in a few
      nucleotides, were isolated from Sida rhombifolia naturally infected with
      SiGMV/Ho(yv). Only SiGMV/Ho(yv) DNA B(2) was able to form a viable
      pseudorecombinant with SiGMV/Co DNA A. In protoplasts, as well as in inoculated
      leaves, SiGMV/Co DNA A trans-replicated the heterogenomic SiGMV/Ho(yv) DNA B(1)
      component, indicating that impaired movement is involved in the deficiency of
      SiGMV/Ho(yv) DNA B(1) to form a pseudorecombinant virus with SiGMV/Co DNA A. Even
      after extensive mutation analysis of SiGMV/Ho(yv) DNA B(1) and B(2), we were
      unable to pinpoint differences in SiGMV/Ho(yv) DNA B(2) that allowed the
      formation of a pseudorecombinant virus with SiGMV/Co DNA A. We observed a gradual
      increase of infectivity from noninfectious SiGMV/Co DNA A/SiGMV/Ho(yv) DNA B(1)
      and B(3) pseudorecombinant virus to pseudorecombinant viruses showing normal
      systemic spread of both genomic components associated with symptomatic plants.

PMID- 10936099
TI  - The master rep concept in nanovirus replication: identification of missing genome
      components and potential for natural genetic reassortment.
AB  - Faba bean necrotic yellows virus (FBYNV), Milk vetch dwarf virus (MDV), and
      Subterranean clover stunt virus (SCSV) are nanoviruses that infect leguminous
      plants. From MDV- and SCSV-infected tissue we identified viral DNAs that encode a
      replication initiator protein (Rep), essential for replication of the multiple
      circular single-stranded DNAs of these viruses. These previously undescribed Rep
      proteins of MDV and SCSV are strikingly similar in sequence and functionally
      equivalent to the master Rep protein of FBYNV. Moreover, we demonstrated that the
      master Rep proteins of the three viruses are able to trigger replication of
      heterologous nanovirus DNAs. Such cross-species replication may reflect a
      considerable potential for genetic reassortment among nanoviruses in nature and
      be of significance for their evolution.

PMID- 10936100
TI  - The Autographa californica nucleopolyhedrovirus IE-1 protein complex has two
      modes of specific DNA binding.
AB  - Missing contact footprinting with formic acid as a modifying reagent was used to
      examine specific IE-1 binding contacts to double-stranded oligonucleotides that
      contained either a consensus hr repeat sequence or a sequence from the pe38
      promoter, which is down regulated by IE-1. The hr repeat sequences contain two
      consensus IE-1 binding motifs (IBMs) flanking a central EcoRI site that are
      oriented in opposite directions with respect to each other. IE-1 was found to
      contact regions including both IBMs. The bases footprinted in the top strand
      included the left IBM (IBM-A), whereas bases in the bottom strand were
      footprinted in a region that included IBM-B and part of IBM-A. When substitution
      mutations were introduced into either IBM, bases on both strands of the remaining
      IBM were strongly footprinted. As with the hr IBM-mutant constructs, bases
      footprinted in the pe38 promoter construct included both strands of the single
      IBM.

PMID- 10936101
TI  - Mutational analysis of the 5' leader region of simian foamy virus type 1.
AB  - The sequence within the 5' untranslated region of the retroviral genome contains
      important cis elements for many steps in viral replication. There is limited
      information available on the role of this region in foamy virus replication.
      Similar to other retroviruses, the 5' untranslated region of foamy viruses
      predicts extensive RNA secondary structure. Serial mutations that could change
      parts of the predicted secondary structure were introduced in the 5' leader
      sequence including the R-U5 region of simian foamy virus type 1 (SFV-1) to
      investigate their role in virus genome packaging and virus replication. Point
      mutations in the R-U5 regions at nucleotide positions 7-12 (I), 241-243 (B), and
      256-257 (D) had no effect on virus replication. Base substitution mutation at
      positions 193-195 (C), however, severely impaired virus replication. Deletion of
      sequences in the leader region, between the primer-binding site and the gag gene,
      at positions 364-399 (d1), 397-435 (d2), or 364-435 (d3), which included
      sequences for RNA genome dimerization, also blocked SFV-1 replication.
      Interestingly, none of these mutations affected genome packaging or the synthesis
      of viral transcripts, suggesting that a step(s) of virus replication following
      packaging is affected. The region between the primer-binding site and the gag
      gene, therefore, is not essential for foamy virus genome packaging. Furthermore,
      the cis-acting elements for genome dimerization and packaging appear to be
      localized in separate regions for foamy viruses.

PMID- 10936102
TI  - Mouse adenovirus type 1 replication in vitro is resistant to interferon.
AB  - The effects of mouse interferon (IFN)-alpha/beta and recombinant IFN-gamma on
      mouse adenovirus type 1 (MAV-1) replication were investigated in single-cycle
      infectious virus yield reduction assays on mouse L929 cells. Viral yields at 3
      days postinfection indicated that wt MAV-1 and pmE314, an early region 3 null
      mutant, were relatively insensitive to both IFN-alpha/beta and IFN-gamma, whereas
      early region 1A (E1A) mutants pmE109 (null), dlE105 (conserved region 1 deletion,
      CR1 Delta), dlE102 (CR2 Delta), and dlE106 (CR3 Delta) were sensitive. MAV-1 E1A
      that was inducibly expressed in mouse fibroblast 37.1 cells rescued vesicular
      stomatitis virus from the antiviral effect of IFN-alpha/beta but not from the
      antiviral effect of IFN-gamma. Interferon-inducible gene expression was reduced
      in 37.1 cells as compared to the parental 3T6 cell line. Steady-state levels of
      IFN-inducible gene mRNAs were also reduced in 3T6 cells infected with the wild
      type virus and pmE314 but not in cells infected with pmE109. These results
      suggest that the MAV-1 E1A gene product is capable of interfering with the
      signaling pathways of both types of IFN, although modulation of IFN-alpha/beta
      antiviral activity was more pronounced.

PMID- 10936103
TI  - Variation in response among individuals to antigenic sites on the HA protein of
      human influenza virus may be responsible for the emergence of drift strains in
      the human population.
AB  - Eight convalescent human sera obtained from patients aged 3 to 14 years old, who
      were infected with influenza A(H3N2) virus during the 1990/1991 influenza season,
      were characterized by a binding assay with chimeric hemagglutinin (HA) proteins
      between influenza virus A/Aichi/2/68 and A/Kamata/14/91(H3N2) strains. These sera
      did not recognize the HA protein of the A/Aichi/2/68 strain but recognized that
      of the A/Kamata/14/91 strain. The binding assay revealed that these sera
      recognized only the HA1 domain of A/Kamata/14/91 HA protein. A further assay of
      the binding of these sera to the chimeric proteins of the HA1 domain revealed
      that three sera (A-1, A-2, and A-3) from very young patients bound only to region
      150-170 (site B1) and one serum (Y-1) bound to regions 96-150 (site A) and 96-170
      (sites A and B1). These four sera showed reduced hemagglutination inhibition (HI)
      activity with the 203v2 strain, a monoclonal variant of the A/Kamata/14/91 strain
      with two amino acid changes in the HA protein at antigenic sites A and B1. The
      other four sera (Y-2, G-1, G-2, and A-4) bound to regions 1-96 (site C/E), 96-150
      (site A), 96-170 (sites A and B1), and 170-200 (site B2), two of which further
      bound to region 240-306 (site C); these sera were all fully reactive with the
      203v2 strain. All eight sera showed reduced HI reactivity to a drift strain
      A/Aichi/4/93. Amino acid changes of the A/Aichi/4/93 strain from the
      A/Kamata/14/91 strain were located at antigenic sites A, B1, B2, and C. We
      propose a possible model for the emergence of a drift strain A/Aichi/4/93 from an
      A/Kamata/14/91-like strain by sequential changes during reinfections of
      individuals starting from A-1-like, next to Y-1-like, and then to Y-2-like
      populations.

PMID- 10936104
TI  - Interaction between HSP70 homolog and filamentous virions of the Beet yellows
      virus.
AB  - An HSP70 homolog (HSP70h), encoded by the Closterovirus Beet yellows virus (BYV),
      functions in viral movement from cell to cell. A previous study revealed that in
      infected cells, HSP70h colocalizes with the masses of BYV filamentous virions.
      Here we demonstrate that HSP70h forms a physical complex with BYV virions. This
      conclusion is based on both the comigration of HSP70h with BYV virions in sucrose
      density gradients and the coimmunoprecipitation of the HSP70h and BYV capsid
      protein using anti-HSP70h serum. The HSP70h-virion complex is stable at high
      concentrations of sodium chloride; its dissociation using sodium dodecyl sulfate,
      lithium chloride, or alkaline pH was accompanied by virion disassembly. However,
      the complex formation does not involve covalent bonds between HSP70h and virion
      components. Each BYV virion contains approximately 10 molecules of HSP70h. The
      possible role of HSP70h interaction with the virions in cell-to-cell movement of
      BYV is discussed.

PMID- 10936105
TI  - Male sperm motility dictated by mother's mtDNA.

PMID- 10936106
TI  - Meiotic studies of a human male carrier of the common translocation, t(11;22),
      suggests postzygotic selection rather than preferential 3:1 MI segregation as the
      cause of liveborn offspring with an unbalanced translocation.
AB  - The t(11;22)(q23;q11) translocation is the only non-Robertsonian rearrangement
      for which there are a large number of unrelated families, apparently with the
      same breakpoints. These families most often have been ascertained through an
      abnormal child with the karyotype 47,XX or XY, +der(22) t(11;22)(q23;q11). To
      explain the high incidence of 3:1 segregants, rarely seen in offspring of
      carriers of other reciprocal translocations, a number of theoretical models have
      been suggested. We have used both electron microscope analysis of the
      synaptonemal complex (SC) and dual-color FISH to investigate the meiotic
      chromosome behavior in a male carrier of the translocation who has the karyotype
      46,XY, t(11;22)(q23;q11). Chromosome synapsis, first-meiotic chiasma
      configuration, and segregation behavior of this translocation have been analyzed
      directly. Examination of SCs by electron microscopy showed pachytene-cross
      formation in 49/50 nuclei. Approximately 50% (26/50) revealed a classical fully
      synapsed quadrivalent. A proportion of these (10/26), however, showed some
      central asymmetry, suggesting heterologous synapsis. The remaining cells appeared
      to have incomplete synapsis. FISH analysis showed only quadrivalents in all 100
      metaphase I nuclei. The chiasma frequency was increased within the interstitial
      segments, in comparison with the same region in normal bivalents. All types of
      segregation category were found in metaphase II nuclei. There was no indication
      of preferential 3:1 anaphase I segregation. We conclude that the +der(22)
      constitution in offspring of carriers of t(11;22)(q23;q11) is not likely to be
      due to meiotic 3:1 segregation being especially common. Rather, the +der(22)
      constitution is more likely to be the result of postzygotic selection against
      other unbalanced karyotypes.

PMID- 10936107
TI  - Human mtDNA haplogroups associated with high or reduced spermatozoa motility.
AB  - A variety of mtDNA mutations responsible for human diseases have been associated
      with molecular defects in the OXPHOS system. It has been proposed that mtDNA
      genetic alterations can also be responsible for sperm dysfunction. In addition,
      it was suggested that if sperm dysfunction is the main phenotypic consequence,
      these mutations could be fixed as stable mtDNA variants, because mtDNA is
      maternally inherited. To test this possibility, we have performed an extensive
      analysis of the distribution of mtDNA haplogroups in white men having fertility
      problems. We have found that asthenozoospermia, but not oligozoospermia, is
      associated with mtDNA haplogroups in whites. Thus, haplogroups H and T are
      significantly more abundant in nonasthenozoospermic and asthenozoospermic
      populations, respectively, and show significant differences in their OXPHOS
      performance.

PMID- 10936108
TI  - Complementation analysis in Fanconi anemia: assignment of the reference FA-H
      patient to group A.
AB  - Fanconi anemia (FA) is an autosomal recessive disorder with diverse clinical
      symptoms and extensive genetic heterogeneity. Of eight FA genes that have been
      implicated on the basis of complementation studies, four have been identified and
      two have been mapped to different loci; the status of the genes supposed to be
      defective in groups B and H is uncertain. Here we present evidence indicating
      that the patient who has been the sole representative of the eighth
      complementation group (FA-H) in fact belongs to group FA-A. Previous exclusion
      from group A was apparently based on phenotypic reversion to wild-type rather
      than on genuine complementation in fusion hybrids. To avoid the pitfall of
      reversion, future assignment of patients with FA to new complementation groups
      should conform with more-stringent criteria. A new group should be based on at
      least two patients with FA whose cell lines are excluded from all known groups
      and that fail to complement each other in fusion hybrids, or, if only one such
      cell line were available, on a new complementing gene that carries pathogenic
      mutations in this cell line. On the basis of these criteria, the current number
      of complementation groups in FA is seven.

PMID- 10936109
TI  - Reality-based medicine.

PMID- 10936110
TI  - Good people with whom to work.

PMID- 10936111
TI  - The expanding role of long-acting beta-agonists.

PMID- 10936112
TI  - Gas exchange kinetics in patients with cardiovascular disease.

PMID- 10936113
TI  - Polysomnography in the diagnosis of the obstructive sleep apnea-hypopnea
      syndrome: where do we draw the line?

PMID- 10936114
TI  - Hemoptysis season.

PMID- 10936115
TI  - Unpredictability of deception in compliance with physician-prescribed
      bronchodilator inhaler use in a clinical trial.
AB  - OBJECTIVE: To identify subject characteristics that may be predictive of
      intentional dumping of metered-dose inhalers (MDIs) during a clinical trial.
      DESIGN: Nebulizer Chronologs (NCs; Medtrac Technologies; Lakewood, CO), which
      record the date and time of each MDI actuation, were attached to the MDIs of
      participants who were given a prescribed medication schedule to follow in a
      clinical trial. Participants were not informed of the function of the NC or that
      their medication use was being monitored. SETTING: The Lung Health Study, a 5
      year clinical trial to evaluate the effect of intensive smoking cessation
      counseling and regular use of an inhaled bronchodilator on the progression of
      COPD. PARTICIPANTS: One hundred one smokers, 35 to 60 years of age, with mild to
      moderate airways obstruction enrolled in The Lung Health Study. MEASUREMENTS AND
      RESULTS: Thirty of these 101 participants (30%) actuated their inhalers > 100
      times within a 3-h interval on at least one occasion during the first year of
      this 5-year trial. Only 1 of an additional 135 participants who had full
      foreknowledge of the MDI monitoring capability of the NC did so. Most of these
      dumping episodes occurred shortly before a clinic follow-up visit, suggesting an
      active attempt to hide noncompliance from the clinic staff. Whereas self-reported
      inhaler usage and canister weights were similar for the "dumpers" and
      "nondumpers," NC data indicated significantly lower compliance rates for dumpers
      (chi(2); p < 0.05). When demographic variables, treatment and clinic assignments,
      smoking status, pulmonary function test results, respiratory symptoms, and
      disease history of dumpers and nondumpers were analyzed, no predictors of dumping
      could be found. CONCLUSIONS: Deception among noncompliers occurs frequently in
      clinical trials, is often not revealed by the usual methods of monitoring, and
      cannot be predicted by data readily available in clinical trials.

PMID- 10936116
TI  - A dose-ranging study of fluticasone propionate administered once daily via
      multidose powder inhaler to patients with moderate asthma.
AB  - STUDY OBJECTIVE: This dose-ranging study evaluated the clinical efficacy and
      safety of inhaled fluticasone propionate administered once daily via a multidose
      powder inhaler in patients with moderate asthma (FEV(1), 45 to 75% predicted).
      MATERIALS AND METHODS: In this multicenter trial, 330 patients (> or = 12 years
      old) previously receiving inhaled corticosteroids or beta(2)-agonists alone were
      randomized in a double-blind manner to receive fluticasone propionate at 100,
      200, or 500 microg once daily or matching placebo for 12 weeks. RESULTS: Once
      daily treatment with fluticasone propionate resulted in an improvement in
      efficacy variables, such as FEV(1), morning and evening peak expiratory flow
      (PEF), asthma symptom scores, nighttime awakenings, albuterol use, and duration
      of study participation. A dose-related trend was observed for improvements in
      morning and evening PEF and albuterol use. Statistical significance for pairwise
      comparisons was achieved for 200 microg and 500 microg fluticasone propionate vs
      placebo for all efficacy variables, and for 100 microg fluticasone propionate vs
      placebo for morning and evening PEF at most or all time points. Drug-related
      adverse events were few (< or = 5%) and mostly related to the topical effects of
      inhaled corticosteroids. No dose-response effect or clinically relevant
      differences were observed in morning plasma cortisol concentrations or after
      cosyntropin stimulation. CONCLUSION: Once-daily treatment with fluticasone
      propionate was well tolerated and demonstrated some dose-related trends in
      improvements in lung function and asthma control in patients with moderate
      asthma.

PMID- 10936117
TI  - Long-term efficacy and safety of fluticasone propionate powder administered once
      or twice daily via inhaler to patients with moderate asthma.
AB  - OBJECTIVE: To evaluate the efficacy and safety of fluticasone propionate
      administered as a once-daily or twice-daily regimen over a period of 1 year to
      patients with moderate asthma. DESIGN: Double-blind, randomized, parallel group,
      and placebo-controlled phase (12 weeks) and an open-label phase (54 weeks).
      SETTING: Multicenter study in an outpatient setting. PARTICIPANTS: Patients (n =
      253; age, > or = 12 years) with a mean FEV(1) of 67% predicted normal were
      stratified according to baseline therapy of maintenance inhaled corticosteroids
      vs beta(2)-agonists alone. MEASUREMENTS AND INTERVENTIONS: Fluticasone propionate
      (250 microg bid or 500 microg qd) or placebo (bid) was administered via the
      Diskus multidose powder inhaler (Glaxo Wellcome; Research Triangle Park, NC) for
      12 weeks. During open-label treatment, patients were re-randomized to once-daily
      or twice-daily fluticasone propionate. RESULTS: Compared to placebo, fluticasone
      propionate administered qd or bid significantly improved FEV(1) (p < 0.001),
      morning (p < 0.001) and evening peak expiratory flow (PEF; p < 0.001), asthma
      symptom scores (p < or = 0.001), and albuterol use (p </= 0.001), and decreased
      nighttime awakenings. By the end of 12 weeks, withdrawal due to lack of efficacy
      was significantly higher in the placebo group than in the once-daily (p = 0.001)
      or twice-daily (p < 0.001) groups. When comparing the two active dosing regimens,
      significant differences in favor of twice-daily dosing were noted in FEV(1),
      albuterol use, and withdrawal due to lack of efficacy. During 54 weeks of open
      label treatment, FEV(1) and PEF continued to improve with both regimens, and
      improvements seen in the first 12 weeks were maintained in patients who switched
      from twice-daily to once-daily dosing. Fluticasone propionate treatment over a 54
      week period was well tolerated, with few drug-related adverse events, which were
      primarily topical effects of inhaled corticosteroids. CONCLUSIONS: Fluticasone
      propionate powder improved lung function when administered either qd or bid over
      a 1-year period to patients with moderate asthma, with twice-daily dosing
      demonstrating significantly greater improvement in some efficacy parameters than
      once-daily dosing over the first 12 weeks of treatment. Fluticasone propionate
      treatment was not associated with significant systemic effects.

PMID- 10936118
TI  - A randomized, placebo-controlled study to evaluate the role of salmeterol in the
      in-hospital management of asthma.
AB  - STUDY OBJECTIVES: To assess the safety and efficacy of salmeterol xinafoate as an
      adjunct to conventional therapy for the in-hospital management of acute asthma.
      DESIGN: A prospective, double-blind, randomized placebo-controlled trial.
      SETTING: Medical wards of a large university-based hospital. PATIENTS: Forty
      three patients admitted for an acute exacerbation of asthma. INTERVENTIONS:
      Salmeterol (42 microg) or two puffs of placebo every 12 h in addition to standard
      therapy (short-acting beta-agonists, corticosteroids, and anticholinergic
      agents). RESULTS: No clinically adverse effects were seen with the addition of
      salmeterol to conventional therapy. After salmeterol, there was no difference in
      pulse, respiratory rate, oxygen saturation by pulse oximetry, severity of
      symptoms, or dyspnea score. Patients receiving salmeterol had greater FEV(1)
      percent improvements than the placebo group at 12, 24, 36, and 48 h. These
      findings were not statistically significant. By paired Student's t tests, there
      were significant improvements in FEV(1) (p = 0.03) and FVC (p = 0.03) in the
      salmeterol group after 48 h of treatment with no comparable improvement in the
      placebo group. In a subgroup analysis of patients with an initial FEV(1) < or =
      1.5 L, the absolute FEV(1) percent improvement for salmeterol vs placebo was 51%
      vs 16% at 24 h and 54% vs 40% at 48 h. The relative FEV(1) percent improvement
      for salmeterol vs placebo was 17% vs 8% at 24 h and 18% vs 14% at 48 h.
      CONCLUSION: The addition of salmeterol to conventional therapy is safe and may
      benefit hospitalized patients with asthma. Further studies are needed to clarify
      its role in the treatment of acute exacerbation of asthma.

PMID- 10936119
TI  - Functional antagonism with formoterol and salmeterol in asthmatic patients
      expressing the homozygous glycine-16 beta(2)-adrenoceptor polymorphism.
AB  - BACKGROUND: Formoterol and salmeterol differ in their relative intrinsic activity
      at airway beta(2)-adrenoceptors, with formoterol being a full agonist. The
      homozygous glycine-16 polymorphism of the beta(2)-adrenoceptor occurs in
      approximately 40% of patients and is known to predispose to agonist-induced
      downregulation and desensitization. OBJECTIVES: To evaluate possible differences
      in intrinsic beta(2)-adrenoceptor agonist activity between salmeterol and
      formoterol in terms of their functional antagonism against methacholine-induced
      bronchoconstriction (the primary end point) in genetically susceptible patients
      who exhibited the homozygous glycine-16 polymorphism. METHODS: Eighteen patients
      with mild-to-moderate persistent asthma receiving inhaled corticosteroid who
      expressed the homozygous glycine-16 genotype were randomized to completion (mean
      [SEM] age, 35.8 [3.2] years; mean FEV(1), 76.9 [2. 5]% predicted). Patients
      received three different treatments for 1 week in randomized, double-blind,
      crossover fashion, with a 1-week washout period between treatments: formoterol,
      12 microg bid; salmeterol, 50 microg bid; and placebo. For each of the randomized
      treatment periods, there were three separate methacholine challenges: baseline
      after washout, 12 h after the first dose, and 12 h after the last dose. RESULTS:
      Both salmeterol and formoterol exhibited significantly (p < 0.05) greater
      bronchoprotection than placebo for their effects after single or repeated dosing,
      although there was no significant difference between the two drugs. The geometric
      mean fold protection vs placebo (95% confidence interval [CI]) for the first dose
      was 1.6-fold (95% CI, 1.1 to 2.2) for salmeterol and 1.9-fold (95% CI, 1.1 to
      3.2) for formoterol, and for last dose was 1.6-fold (95% CI, 1.2 to 2.3) for
      salmeterol and 1. 9-fold (95% CI, 1.2 to 2.8) for formoterol. Salmeterol and
      formoterol produced significant (p < 0.05) increases in FEV(1) and forced
      expiratory flow after 25 to 75% of vital capacity has been expelled, after the
      first but not the last dose compared to placebo, while there were significant (p
      < 0.05) improvements in domiciliary peak flows during treatment with both drugs.
      CONCLUSION: Our results showed no difference between formoterol and salmeterol in
      the degree of functional antagonism against methacholine-induced
      bronchoconstriction at the end of a 12-h dosing interval in patients who
      expressed the homozygous glycine-16 genotype. There was a significant residual
      degree of bronchoprotection after 1 week of treatment, which was not
      significantly different compared to the first-dose effect.

PMID- 10936120
TI  - Percutaneous transluminal coronary angioplasty improves oxygen uptake kinetics
      during the onset of exercise in patients with coronary artery disease.
AB  - STUDY OBJECTIVES: Although percutaneous transluminal coronary angioplasty (PTCA)
      is known to have beneficial effects on exercise capacity, its effects on the
      cardiovascular response during the onset of exercise have not been clarified. The
      present study was undertaken to determine the effects of PTCA on the kinetics of
      oxygen uptake (VO(2)) during constant-work-rate exercise in patients with
      coronary artery disease, as well as on their indexes of maximal work capacity.
      METHODS: Seventeen patients with coronary artery disease who received successful
      PTCAs performed a 50-W constant-work-rate exercise test for 6 min and a symptom
      limited incremental exercise test both before and 4 months after the PTCA
      procedure. VO(2) was calculated from breath-by-breath analysis of respired gases.
      The time constant of VO(2) kinetics during the onset of 50-W exercise was
      determined by fitting a single exponential function to the VO(2) response.
      RESULTS: In 14 patients without coronary restenosis, the time constant of VO(2)
      kinetics was significantly shortened from (mean +/- SD) 57.4 +/- 12.6 before PTCA
      to 48.2 +/- 9.5 s after PTCA (p = 0. 0035), indicating improved kinetics of the
      VO(2) response. In these subjects, the peak VO(2) obtained during maximal
      exercise testing also increased from 23.1 +/- 3.5 to 26.5 +/- 3.2 mL/min/kg,
      respectively (p = 0.0005). However, there was no improvement in these indexes in
      the patients who had restenosis after undergoing PTCA (n = 3). CONCLUSION:
      Indexes of cardiopulmonary exercise testing, which reflect an efficiency of
      oxygen flow to the exercising muscle, can be used as an objective, noninvasive,
      and cost-effective guide for understanding which patients will not have coronary
      restenosis following PTCA.

PMID- 10936121
TI  - The clinical significance of reversed flow in the main pulmonary artery detected
      by doppler color flow imaging.
AB  - BACKGROUND: Using Doppler color flow imaging, abnormal flow patterns were
      reported to occur with pulmonary artery (PA) dilation. We have frequently
      observed red signals in the main PA, suggesting reversed flow (RF) in patients
      without overt pulmonary hypertension. The clinical implication of these signals
      has not been extensively studied. PATIENTS AND METHODS: We studied 191 of 412
      patients referred for echocardiography (99 men and 92 women; mean +/- SD age, 62
      +/- 13 years), in whom the main PA diameter had been adequately measured. If a
      red signal was observed by color flow imaging, a pulsed Doppler echocardiogram of
      the red signal was recorded simultaneously. The presence of the red signal was
      correlated with the PA diameter and the PA systolic pressure determined using the
      modified Bernoulli equation. In 54 patients who also underwent cardiac
      catheterization studies, the red signal was correlated with PA and pulmonary
      capillary wedge (PCW) pressures, and with pulmonary vascular resistance. RESULTS:
      Red signals adjacent to the medial PA border were detected in parallel with
      systolic blue signals in 127 patients (66%). Pulsed Doppler recordings revealed
      that they were caused by RF occurring immediately after the forward systolic
      signal and persisted in diastole. The PA diameter (28 +/- 4.8 mm) and the
      estimated PA systolic pressure (34 +/- 16 mm Hg) of patients with the RF signal
      were significantly greater (p < 0.001 and p < 0.05, respectively) than those of
      patients without the signal (22 +/- 2.5 mm and 28 +/- 6.0 mm Hg, respectively).
      Among patients who had hemodynamic studies, PA and PCW pressures were
      significantly higher (p < 0.05) in the 41 patients with the RF signal (22 +/- 12
      mm Hg vs 15 +/- 2.6 mm Hg and 11 +/- 5.5 mm Hg vs 8 +/- 3.1 mm Hg, respectively).
      CONCLUSION: : RF signals in the main PA occur mostly as a result of PA dilation,
      which may be caused by primary pulmonary hypertension or chronic elevation of
      left atrial pressure in left-sided cardiac abnormalities.

PMID- 10936122
TI  - Evaluation of myocardial injury following repeated internal atrial shocks by
      monitoring serum cardiac troponin I levels.
AB  - INTRODUCTION: Electrical shocks delivered for atrial cardioversion (CV) may cause
      myocardial damage. The aim of this study was to assess the extent of myocardial
      injury caused by repeated intracardiac shocks delivered for low-energy internal
      atrial CV. METHODS AND RESULTS: Thirty-five patients with chronic persistent
      atrial fibrillation (AF) of different etiologies underwent CV with delivery of
      synchronized biphasic shocks (3.0/3.0 ms) between two catheters positioned in the
      right atrium and the coronary sinus. Shocks were delivered according to a step-up
      protocol (50 V, 180 V, then steps of 40 to 56 V up to 500 V, if necessary). In 23
      patients, AF was reinduced after baseline CV, and CV was repeated. Myocardial
      injury was monitored by measuring cardiac troponin I (cTnI) serum concentrations
      in blood samples taken at baseline and at 2, 4, 8, 12, and 24 h after the
      procedure, by means of an immunoenzymologic assay (normal values, < or =0.6
      ng/mL). A mean (+/- SD) of 6.9 +/- 3.4 shocks per patient were delivered (range,
      2 to 17). Shocks delivered in each patient had a maximal energy of 7.3 +/- 4.0 J
      (range, 1.7 to 15.7). In 20 patients (57%), no evidence of myocardial injury
      (cTnI level, < or = 0.6 ng/mL) was found. In 13 patients (37%), mildly elevated
      cTnI levels (range, 0.7 to 1.4 ng/mL) in samples taken 4 to 12 h after CV
      suggested minor myocardial injury. In two patients (6%), higher cTnI levels were
      found in samples taken 4 to 8 h after CV (peak, 1.7 and 2.4 ng/mL), indicating a
      necrotic damage. Patients with no cTnI elevation, with mild cTnI elevation, or
      with cTnI levels >or =1.5 ng/mL did not differ significantly with respect to the
      total number of shocks delivered, the mean amount of energy delivered, and the
      cumulative amount of energy delivered. No clinical complications were observed.
      CONCLUSIONS: Following internal CV with the delivery of repeated shocks, minor
      elevations of cTnI serum levels could be detected in a significant proportion of
      patients, and this suggests subtle asymptomatic minor myocardial injury. The
      elevations of cTnI levels do not appear to be related to the number of shocks or
      to the amount of energy delivered.

PMID- 10936123
TI  - Analysis of physician ability in the measurement of pulsus paradoxus by
      sphygmomanometry.
AB  - CONTEXT: Measurement of pulsus paradoxus (PP) is one of several measures
      previously advocated in the National Heart, Lung, and Blood Institute asthma
      management guidelines: a pulsus of > 12 mm Hg warranted hospital admission. It is
      one of only a few measures that is not effort dependent and therefore important
      in the evaluation of patients with asthma. OBJECTIVE: Determination of physician
      accuracy in measuring PP. DESIGN: A model of induced PP in a trained healthy
      subject without respiratory disease was constructed with a fixed inspiratory
      resistance with measurement of inspiratory air pressure and beat-to-beat BP
      noninvasively. SETTING: Laboratory. PARTICIPANTS: Attending physicians from
      emergency medicine and critical care disciplines who served as consecutive
      examiners of the trained reference subject generating known PP. INTERVENTIONS: A
      total of 19 attending physicians were assessed for ability in measuring PP by
      sphygmomanometry and by palpation. The reference subject generated 4 degrees of
      PP sequentially, with each examiner blinded to the value of negative inspiratory
      pressure and PP. Examiners first assessed PP qualitatively by palpation, followed
      by its measurement within 2 min. MAIN OUTCOME MEASURE: Proximity of physician
      measured PP (PPm) to true PP (PPt). RESULTS: At inspiratory pressures of - 10, -
      15, - 20, and - 25 mm Hg, PPt was 13.7, 16.2, 19.1, and 20.7 mm Hg, respectively
      (F = 14.8, p < 0. 0001; analysis of variance [ANOVA]). At the same pressures, PPm
      was 13.1, 17.5, 17.7, and 18.0 mm Hg (p > 0.10; ANOVA). Linear regression of PPm
      against PPt for each examiner revealed a slope (SE) of 0.53 (0.23), and not a 1:1
      relationship. CONCLUSIONS: Past and present guidelines do not account for the
      challenges in measuring PP, especially in tachypneic patients. Sphygmomanometric
      determination of PP should be augmented by new aids developed through
      technological innovation.

PMID- 10936124
TI  - Mild to moderate sleep respiratory events: one negative night may not be enough.
AB  - STUDY OBJECTIVES: Reports on the reproducibility of apnea-hypopnea indexes (AHIs)
      across sequential polysomnography (PSG) sessions are conflicting, leading to a
      lack of clear recommendations on the optimal use of this technique: is one night
      of monitoring sufficient or is a second night required in order to safely reject
      the diagnosis? DESIGN: Retrospective comparison of two consecutive nights.
      SETTING: Sleep unit of a tertiary-care facility. PATIENTS: Two hundred forty
      three subjects with suspected sleep apneas. INTERVENTIONS: Two sequential PSG
      sessions in a sleep unit. MEASUREMENTS AND RESULTS: Using analysis of covariance
      for repeated measures, with age and body mass index as covariates and gender as a
      cofactor, a classic first-night effect was found for sleep variables. In
      addition, a night effect was demonstrated for sleep respiratory variables.
      Moreover, the high variability of AHIs showed that many patients had their
      condition diagnosed on only one of the two nights, and more often on the second
      night than on the first. The gain in detection by adding a second night when the
      results of testing on the first were negative was between 15% and 25%, according
      to the AHI obtained on night 1. CONCLUSIONS: Considering the disability
      associated with sleep apnea/hypopnea syndrome, as well as its global cost for
      society, the present study shows that it is worth performing two consecutive PSG
      sessions or at least a second one when the result of the first one is negative in
      all patients admitted for apnea detection.

PMID- 10936125
TI  - Should children with suspected obstructive sleep apnea syndrome and normal nap
      sleep studies have overnight sleep studies?
AB  - STUDY OBJECTIVES: Overnight polysomnography (ONP) is the "gold standard" for the
      diagnosis of sleep-disordered breathing, but it is expensive and time-consuming.
      Thus, daytime nap studies have been used as screening tests. If the findings of a
      nap study are normal or mildly abnormal, should ONP be performed? Do specific
      abnormalities in nap studies predict abnormal findings in ONP? To answer these
      questions, we conducted this study. DESIGN: Retrospective chart review. SETTING:
      Children's hospital. PARTICIPANTS: One hundred forty-three children with
      suspected obstructive sleep apnea syndrome secondary to isolated adenotonsillar
      hypertrophy, who had normal or mildly abnormal nap studies, and underwent ONP.
      MEASUREMENTS AND RESULTS: We compared daytime nap and overnight polysomnograms in
      143 children (52 girls; mean [+/- SD] age, 5.6 +/- 3.1 years). Total sleep time
      was 1 h in daytime nap, and 5.1 +/- 1.3 h in ONP. The interval between the two
      studies was 5.9 +/- 4.8 months. The findings of 59% of the nap studies were
      mildly abnormal, while 66% of overnight studies were abnormal. No individual nap
      study parameter (including short obstructive apneas, hypopneas, hypoxemia,
      hypoventilation, snoring, paradoxical breathing, gasping, retractions) had good
      sensitivity at predicting abnormal overnight polysomnograms, but most had good
      specificity and positive predictive value. CONCLUSIONS: We conclude that
      individual nap study parameters are not very sensitive in predicting abnormal ONP
      findings. However, when nap study parameters are abnormal, the chance of
      obstructive sleep apnea syndrome is high.

PMID- 10936126
TI  - Effects of nasal prongs on nasal airflow resistance.
AB  - STUDY OBJECTIVES: The aim of this study was to investigate whether nasal prongs,
      which have been proposed to assess nasal flow during sleep, affect nasal airflow
      resistance (NR). DESIGN: NR was estimated by posterior rhinomanometry at a 0.5
      L/s flow, under eight conditions: in the basal state, and with seven different
      nasal prongs. PARTICIPANTS: The study was performed in 17 healthy supine
      subjects, 8 of whom had basal NR values within the normal range (< or = 2 cm
      H(2)O.L(-1).s, group 1), and 9 had increased basal NR values (> 2.5 cm H(2)O.L(
      1).s, group 2), because of nare narrowness and/or deviated nasal septum.
      MEASUREMENTS AND RESULTS: NR increased significantly while breathing with nasal
      prongs (p < 0.0001 in both groups). The changes in NR (DeltaNR) induced by the
      different nasal prongs were characterized by large intersubject and intrasubject
      variability, with a maximum DeltaNR of 24.2 cm H(2)O.L(-1).s. Significant
      differences were found between the DeltaNR induced by the different nasal prongs
      (p < 0.001 in group 1, and p < 0.0003 in group 2), and for six of them, DeltaNR
      was significantly higher in group 1 than in group 2 (p < 0.02). CONCLUSIONS: This
      study demonstrates that nasal prongs can markedly increase NR in subjects
      presenting with nare narrowness and/or deviated nasal septum. Further
      investigations that would include nocturnal polysomnography are still required to
      evaluate the possible influence of nasal prongs on the diagnosis of obstructive
      sleep apnea syndrome and its severity.

PMID- 10936127
TI  - Sleepiness, fatigue, tiredness, and lack of energy in obstructive sleep apnea.
AB  - STUDY OBJECTIVES: Sleepiness is a key symptom in obstructive sleep apnea syndrome
      (OSAS) and can be objectively assessed with a multiple sleep latency test (MSLT).
      We studied the terms that patients prefer to describe their symptoms-sleepiness,
      fatigue, tiredness, or lack of energy-and how these terms relate to objective
      findings. DESIGN: Observational. SETTING: University-based sleep laboratory.
      PATIENTS: Consecutive OSAS patients referred for diagnostic polysomnography and
      an MSLT. METHODS: Data were obtained from sleep studies and questionnaires.
      RESULTS: Subjects included 117 men and 73 women, with a mean (+/- SD) age of 49
      +/- 13 years, an apnea and hypopnea rate of 32 +/- 28/h of sleep, and an MSLT
      mean sleep latency of 7 +/- 5 min. Subjects more frequently reported problems
      with fatigue, tiredness, and lack of energy than sleepiness (57%, 61%, and 62% vs
      47%). When required to select the one most significant symptom, more patients
      chose lack of energy (about 40%) than any other problem, including sleepiness
      (about 22%). Objective measures of sleepiness and apnea severity showed little or
      no association with any symptom, but female gender showed significant
      associations with each. CONCLUSIONS: Complaints of fatigue, tiredness, or lack of
      energy may be as important as that of sleepiness to OSAS patients, among whom
      women appear to have all such complaints more frequently than men. The diagnosis
      of OSAS should not be excluded based only on a person's tendency to emphasize
      fatigue, tiredness, or lack of energy more than sleepiness.

PMID- 10936128
TI  - Can CT scanning be used to select patients with unilateral primary spontaneous
      pneumothorax for bilateral surgery?
AB  - STUDY OBJECTIVES: Despite advances in the surgical treatment of spontaneous
      pneumothorax, the timing of surgical intervention continues to be a subject of
      controversy. We test the hypothesis that CT scanning can help to predict the
      probability of the occurrence of primary spontaneous pneumothorax (PSP) by
      detecting lung bullae. DESIGN: Prospective, longitudinal cohort study. PATIENTS
      AND METHODS: Between May 1994 to March 1995, 28 consecutive patients (23 men; age
      range, 18 to 47 years; mean, 29 years) with unilateral PSP who were to undergo
      video-assisted thoracic surgery (VATS) received preoperative CT of the thorax. CT
      scans were interpreted by one radiologist blinded to the clinical data for the
      presence of bullae in both lungs. All patients were followed-up in our outpatient
      clinic for an average of 59.0 months (range, 54 to 64 months). RESULTS: Eighty
      eight percent of the blebs or bullae identified intraoperatively were
      demonstrated on preoperative CT scans. CT scans also showed the presence of lung
      blebs or bullae in the contralateral lung in 15 patients (53.6%). During the
      follow-up period, 4 of these 15 patients (26.7%) with contralateral blebs
      developed PSP in the untreated lung; none of the patients who did not have
      contralateral blebs (n = 13) developed PSP (p = 0.04 [chi(2) analysis]).
      CONCLUSIONS: The detection of lung bullae by CT scanning in the contralateral
      lung following unilateral PSP is associated with a higher rate of subsequent
      occurrence of pneumothorax in that lung. Thus, CT scanning can be used to predict
      the risk of occurrence of this condition, allowing preemptive surgical
      intervention in selected patients.

PMID- 10936129
TI  - Exercise capacity of thoracotomy patients in the early postoperative period.
AB  - OBJECTIVE: We investigated the mechanism involved with the initial drop and
      subsequent recovery of exercise capacity in the early postoperative period of
      thoracotomy patients. METHODS: Sixteen patients (13 who had undergone lobectomy,
      3 who had undergone pneumonectomy) underwent a routine pulmonary function test
      (PFT) and a cardiopulmonary exercise test preoperatively, within 14 postoperative
      days (POD; post-1; mean +/- SD, 9 +/- 2 POD), and after 14 POD (post-2; mean, 26
      +/- 12 POD). RESULTS: After surgery on post-1, PFT results of FVC, FEV(1), and
      maximum ventilatory volume (MVV) significantly decreased. Oxygen uptake (VO(2))
      at a venous blood lactate level of 2.2 mmol/L (La-2. 2), which was adopted as the
      empirical anaerobic threshold, and maximum V O(2) (VO(2)max) decreased
      significantly to 88.2 +/- 7.9% and 73.1 +/- 15.4% of the preoperative values,
      respectively. La-2.2 min ventilation (VE)/ MVV and maximum VEmax)/MVV increased
      significantly from 0.36 +/- 0.08 to 0. 66 +/- 0.20 and from 0.58 +/- 0.14 to 0.80
      +/- 0.09, respectively. On post-2, though La-2.2 VO(2) did not change, VO(2)max
      improved significantly to 81.5 +/- 19.7% of the preoperative values, in
      association with significant increases in maximal tidal volume and VEmax, which
      were produced by significant increases in the PFT results. La-2.2 VE/MVV also
      decreased significantly to 0.49 +/- 0.13, which indicated a sufficient recovery
      of respiratory reserve at submaximal exercise. CONCLUSIONS: The initial drop of
      exercise capacity after lung resection seems to be derived from both circulatory
      and ventilatory limitations. Further, the subsequent recovery within 1 month
      seems to be produced by an improvement in ventilatory limitation, which was
      caused by the surgical injury to the chest wall.

PMID- 10936130
TI  - Pain location, distribution, and intensity after cardiac surgery.
AB  - STUDY OBJECTIVES: To study the location, distribution, and intensity of pain in a
      sample of adult cardiac surgery patients during their postoperative hospital
      stay. DESIGN: In a prospective study, pain location, distribution (number of pain
      areas per patient), and intensity (0 to 10 numerical rating scale) were
      documented on the first, second, third, and seventh postoperative day (POD).
      Patient characteristics (age, sex, size, and body mass index) were analyzed for
      their impact on pain intensity. SETTING: A university hospital. PATIENTS: Two
      hundred consecutive adult patients who underwent median sternotomy for open heart
      surgery. There were 121 male and 79 female patients, with a mean (+/- SD) age of
      60.9 +/- 19.2 years. MEASUREMENT AND RESULTS: The maximal pain intensity was
      significantly higher on POD 1 and 2 (3.7 +/- 2 and 3.9 +/- 1.9, respectively) and
      lower on POD 3 and 7 (3.2 +/- 1.5 and 2.6 +/- 1.8, respectively). The pain
      distribution did not vary significantly throughout the hospital stay, but the
      location did, with more shoulder pain on POD 7. Only age was found to have an
      impact on pain intensity, with patients < 60 years having a higher pain intensity
      than older patients on POD 2 (4.3 +/- 2.2 vs 3.6 +/- 2.4; p = 0.02). CONCLUSIONS:
      In this patient population, the pain intensity diminished from POD 3 onward,
      although its distribution did not vary significantly during the first
      postoperative week. Moreover, pain location changed with time, with more
      osteoarticular type pain at the end of the first postoperative week. Among the
      patients' characteristics, only younger age had an impact on pain intensity, with
      a higher value on POD 2.

PMID- 10936131
TI  - The clinical and economic impact of deep chest surgical site infections following
      coronary artery bypass graft surgery.
AB  - STUDY OBJECTIVES: To examine how deep chest surgical site infections following
      coronary artery bypass graft (CABG) surgery impact hospital inpatient length of
      stay (LOS), costs, and mortality. SETTING: A large, Midwestern community medical
      center. DESIGN: All CABG patients who developed deep chest infection (n = 41)
      were compared to a set of control subjects (n = 160) systematically selected as
      every tenth uninfected CABG patient. Clinical data were abstracted from patient
      records, and cost information was obtained from the cost accounting database of
      the hospital. RESULTS: Variables that significantly increased the risk of deep
      chest surgical site infection included obesity (odds ratio [OR], 11; p = 0.
      0001), renal insufficiency (OR, 8.9; p = 0.0001), connective tissue disease (OR,
      25.4; p = 0.0003), reexploration for bleeding (OR, 8.2; p = 0.0015), and the
      timing of antibiotic prophylaxis (> 60 min before incision; OR, 5.3; p = 0.0128).
      Within 1 year postoperatively, patients with deep chest surgical site infection
      had a mortality rate of 22%, vs 0.6% for uninfected patients (p = 0.0001).
      Infected patients also incurred an average of 20 additional hospital days (p =
      0.0001). Univariate analysis indicated that patients who developed deep chest
      surgical site infection incurred $20,012 in additional costs in the first year (p
      = 0.0001). Infected patients who died incurred on average $60,547 more than
      infected patients who survived (p = 0.034). Multivariate analysis confirmed the
      magnitude of the estimate of the cost for deep chest surgical site infection
      ($18, 938; p = 0.0001). CONCLUSIONS: Deep chest surgical site infections
      following CABG surgery are associated with significant increases in LOS,
      hospitalization costs, and mortality. These results suggest the need for improved
      infection control measures to reduce deep chest surgical site infection rates.

PMID- 10936132
TI  - Aspergillus and endobronchial abnormalities in lung transplant recipients.
AB  - STUDY OBJECTIVE: To determine the relationship between aspergillus recovery from
      the airways of lung transplant recipients and the development of endobronchial
      abnormalities. DESIGN: Retrospective case series. SETTING: Tertiary-care
      hospital. PATIENTS: All patients who underwent lung transplantation between
      December 1991 and June 1999. MEASUREMENTS AND RESULTS: The study cohort included
      38 patients. The primary end point was the bronchoscopic identification of an
      endobronchial abnormality. Aspergillus was isolated from the lungs of nine
      patients (23.7%). Most of these isolates occurred early after transplantation
      (mean, 8 weeks). Endobronchial abnormalities arose in seven of the patients
      (18.4%) and manifested as either exuberant granulation tissue or stricture
      formation. Six of the 9 (66.6%) patients with aspergillus developed airway
      lesions, compared to 1 of the 29 patients (3.4%) without aspergillus (p =
      0.0002). Endobronchial abnormalities were 19.3 times more likely to occur in
      patients in whom aspergillus had previously been isolated. As a screening test
      for the subsequent diagnosis of an airway complication, the recovery of
      aspergillus had a sensitivity and specificity of 85.7% and 90.3%, respectively.
      These aspergillus-related endobronchial abnormalities were clinically relevant as
      evidenced by a mean increase of 25.9% in the FEV(1) after bronchoscopic
      intervention. CONCLUSION: The early isolation of aspergillus from the airways of
      lung transplant recipients identifies patients at increased risk for the
      development of clinically significant endobronchial abnormalities.

PMID- 10936133
TI  - Psychological functioning and quality of life in lung transplant candidates and
      recipients.
AB  - OBJECTIVE: The purpose of this study was to examine the psychological functioning
      and quality of life (QOL) of lung transplant candidates and recipients. METHODS:
      The following measures were completed by 36 lung transplant candidates (the
      pretransplant group [PRE]) and 73 recipients (the posttransplant group [POST]):
      the Rand-36 Item Health Survey 1.0 (RAND-36), visual analog scale of overall QOL
      (OQOL), Brief Symptoms Inventory (BSI), Derogatis Sexual Functioning Inventory
      (DSFI), Hospital Anxiety and Depression Scale (HAD), Rosenberg Self-Esteem Scale
      (RSES), and Body Cathexis Scale (BC). RESULTS: Compared to the PRE, POST patients
      had significantly better scores on the following measures: RAND-36 total,
      physical health, role limitations due to physical health, general health,
      vitality, and social functioning subscales (all p < 0.0001); visual analog scale
      of OQOL (p < 0.0001); BSI (p < 0.05); BC (p < 0.05); HAD anxiety (p < 0.05) and
      depression (p < 0.0001); and RSES (p < 0.05). Despite better scores, some areas
      did not differ between the PRE and the POST, and many patients continued to
      experience impairments in psychological functioning. Specifically, the RAND-36
      emotional health and role limitations due to emotional health subscale scores did
      not differ between the PRE and the POST and they remained lower than published
      norms. A significant proportion of patients in both groups (44% of PRE patients
      and 28% of POST patients) had borderline or clinical levels of anxiety (ie, the
      HAD). Finally, PRE and POST mean scores were significantly lower than published
      norms on the RSES (p < 0.05) and the body image scale of the DSFI (p < 0.05).
      CONCLUSIONS: Although lung transplant recipients have better general, physical,
      and psychological health than their pretransplant counterparts, the present
      research suggests that both groups experience impairment in several areas of
      psychological functioning. Future research into the QOL of the lung transplant
      population should be aimed at recognizing, intervening, and improving patients'
      psychological and emotional well-being.

PMID- 10936134
TI  - Outpatient pleurodesis of malignant pleural effusions using a small-bore pigtail
      catheter.
AB  - STUDY OBJECTIVE: Patients with symptomatic malignant pleural effusion are usually
      treated with large-bore chest tube placement and pleurodesis requiring > or = 3
      days of hospitalization. We sought to demonstrate the feasibility of ambulatory
      drainage and sclerosis using a small-bore pigtail catheter in patients with
      malignant pleural effusions. We reasoned that this approach would improve
      symptoms and quality of life at a reduced cost. METHODS: A 14F pigtail catheter
      was percutaneously inserted into the pleural space and connected to a closed
      gravity-drainage bag system. The patients were instructed in the use of the
      drainage system and discharged to return for sclerosis with 4 g of talc after the
      drainage was < 100 mL/24 h. Patients were graded for dyspnea and performances
      status using the Eastern Cooperative Oncology Group score (ECOG) and baseline and
      transitional dyspnea index score (BDI-TDI) before tube placement and again at 30
      days. Radiographic response was graded as total response, partial response, or
      failure. Telephone follow-up was initiated when the patient could not return for
      evaluation. RESULTS: Ten ambulatory women, ages 41 to 79 years, were enrolled.
      The chest tube was left in place from 1 to 10 days, draining a mean of 2,956 mL
      (1,685 to 6,050 mL). Only two patients were unable to undergo sclerosis owing to
      catheter dislodgment and minimal drainage. Six reported symptomatic improvement
      at 30 days confirmed by TDI and ECOG scores in four of six. One with a prior
      history of a lobectomy was found to have a chylous pleural effusion and
      experienced a hydropneumothorax, for which sclerosis was unsuccessful. One died
      in hospital on day 26 after sclerosis despite radiographic resolution. Of the
      four patients who had improved dyspnea and functional status by TDI and EGOG
      scores, radiographic response was complete in three and partial in one. Two of
      the six were not able to return for follow-up because of weakness but reported
      improvement by telephone inquiry. CONCLUSION: Ambulatory sclerosis of malignant
      effusion using a small-bore catheter is a feasible alternative to inpatient
      sclerosis with a large-bore chest tube, especially in patients with strong
      preferences for outpatient care.

PMID- 10936135
TI  - Efficacy and tolerance of a new silicone stent for the treatment of benign
      tracheal stenosis: preliminary results.
AB  - STUDY OBJECTIVE: In inoperable patients with tracheal stenosis who are treated
      using silicone stents, stent migration occurs in 18.6% of cases. To decrease the
      migration rate, we have designed a new silicone stent with narrow central and
      larger distal parts. This study analyzes the stability and tolerance of this new
      stent. DESIGN: Preliminary prospective study conducted in two French university
      hospitals. PATIENTS: Thirteen inoperable patients with benign complex tracheal
      stenosis due to intubation or tracheotomy. INTERVENTIONS: Tracheal stent
      insertion was performed under general anesthesia with a rigid bronchoscope. The
      patients were followed up clinically up to stent removal, which was planned at 18
      months. RESULTS: Stent insertion or removal was very simple and did not differ
      from other silicone stents. No migration occurred after a mean follow-up of 22.8
      months. Minimal granuloma formation occurred in only one patient (7.7%). Sputum
      retention remained similar to that with other silicone stents and could be
      improved by a smoother internal wall. Stents have been removed in seven patients
      after a mean duration of 19.6 months, with a complete stenosis cure in four
      cases. CONCLUSION: This new stent combines the excellent stability of the
      metallic stents and the tolerance and easy removal of straight silicone stents.
      This allows a prolonged use in order to obtain curative action.

PMID- 10936136
TI  - Health status and sociodemographic characteristics of adults receiving a cystic
      fibrosis diagnosis after age 18 years.
AB  - OBJECTIVES: An increasing percentage of cystic fibrosis (CF) diagnoses are
      occurring in adulthood. The purpose of this study was to explore how age at
      diagnosis may be associated with selected disease and sociodemographic
      characteristics. DESIGN: The 1996 Cystic Fibrosis Foundation (CFF) Patient
      Registry data were analyzed to test for associations between age at diagnosis and
      selected variables. All cases involved individuals > or = 18 years who were
      represented in the CFF Patient Registry for 1996. Patients were assigned to one
      of two groups: those diagnosed with CF after age 18 years (n = 786) and those
      diagnosed before 18 years (n = 6,641). RESULTS: In 1996, the incidence of late
      diagnosis was 7.8%, and the prevalence was 10.9%. The mean age of late diagnosis
      was 27 years. Respiratory symptoms most frequently led to late diagnosis.
      Patients receiving a late CF diagnosis were less likely to have alleles for Delta
      F508. There was no correlation between age at diagnosis and percent predicted
      FEV(1), although patients in the late-diagnosis group were an average of 10 years
      older than those in the early-diagnosis group. Late diagnosis was associated with
      fewer complications, fewer hospitalizations, less oxygen use, fewer courses of
      home IV treatment, and less enzyme use. Women were most often diagnosed late. Men
      displayed more diversity in conditions leading to diagnosis. Psychosocially,
      those patients receiving late diagnoses were more likely to be college graduates,
      married, and employed full time. For those adults who died in 1996, there was a
      positive association between their age at diagnosis and age at death. CONCLUSION:
      Those patients diagnosed with CF as adults differ, both medically and
      psychosocially, from those diagnosed at a younger age; these differences have
      implications for diagnosis, treatment, and education.

PMID- 10936137
TI  - Bone histomorphometry in adult patients with cystic fibrosis.
AB  - STUDY OBJECTIVE: Low bone mineral density is a common complication of cystic
      fibrosis (CF), and recent studies have implicated vitamin D insufficiency as a
      significant etiologic factor. The aim of this study was to establish whether
      there was bone biopsy evidence of vitamin D deficiency osteomalacia in patients
      with CF and to document the general histomorphometric characteristics of CF bone.
      PATIENTS AND METHODS: A retrospective descriptive and histomorphometric study of
      postmortem L2/L3 vertebral bone biopsy specimens was undertaken on tissue from 11
      posttransplant CF patients and 4 nontransplanted CF patients. Control data were
      derived from postmortem bone specimens from 15 young adults. RESULTS: Bone from
      all CF patients was characterized by severe osteopenia in both trabecular and
      cortical bone. At the cellular level, there was decreased osteoblastic and
      increased osteoclastic activity. The reduction in osteoblastic activity was due
      to both a decrease in osteoblast number and a decrease in the biosynthetic
      potential of osteoblasts. The osteoclastic changes were due to an increase in the
      number of osteoclasts. The increase in osteoclasis and the uncoupling of
      osteoblastic and osteoclastic activity resulted in an increase in resorptive
      surfaces. Although there were few significant differences between the
      transplanted and nontransplanted CF groups, both cortical and trabecular bone
      mass tended to be lower after transplantation. None of the CF undecalcified
      biopsy specimens showed osteoid parameters characteristic of vitamin D deficiency
      osteomalacia. CONCLUSIONS: CF patients have an unusual and complex pattern of
      cellular changes within bone that are not typical of vitamin D deficiency
      osteomalacia.

PMID- 10936138
TI  - Seasonal variation in cryptogenic and noncryptogenic hemoptysis hospitalizations
      in France.
AB  - STUDY OBJECTIVE: To determine the potential role of seasonality in
      hospitalizations for cryptogenic and noncryptogenic hemoptysis in the French
      population. DESIGN: Retrospective analysis of hospital discharge data from a
      National Register. SETTING: All 29 French university hospitals, between July 1,
      1994, and June 30, 1997. PATIENTS: Two thousand six hundred seventy-seven and
      3,672 adult hospitalizations for cryptogenic and other hemoptysis, respectively.
      MEASUREMENTS: Cumulative monthly averages were determined, expressed as the
      percentage above or below the average monthly value during the entire study
      period. RESULTS: The distribution of cumulative monthly hospitalizations for
      cryptogenic hemoptysis peaked in March (32% above the average) and was lowest in
      summer (30% below the average; p < 0.001). Hospitalizations for noncryptogenic
      hemoptysis followed a similar seasonal pattern (p < 0. 001). In the 16- to 34
      year-old individuals, cryptogenic hemoptysis, compared with noncryptogenic
      hemoptysis, showed a higher incidence with a larger seasonal amplitude (p <
      0.001). CONCLUSIONS: A better understanding of the fundamental pathophysiologic
      mechanisms underlying this respiratory and hemorrhagic condition may be helpful
      in developing preventive measures, especially in patients with a risk of
      recurrence.

PMID- 10936139
TI  - Serum KL-6 concentrations in dairy farmers.
AB  - STUDY OBJECTIVES: Serum KL-6 (Krebs von den Lungen-6) has been recognized to be a
      marker for the activity of diffuse interstitial lung diseases. The purpose of the
      study is to evaluate serum KL-6 measurement as a marker for farmer's lung disease
      (FLD). DESIGN: A cross-sectional survey of a cohort of dairy farmers.
      Retrospective measurement of KL-6 stored serum samples from those dairy farmers
      previously screened for FLD. SETTING: University hospital screening project for
      FLD within a dairy-farming community in Japan. PARTICIPANTS: Four hundred seventy
      two dairy farmers were invited to attend a local clinic. MEASUREMENTS AND
      RESULTS: We examined serum KL-6 concentrations in 272 farmers. Subjects were
      classified into three groups: (1) 5 farmers with FLD, (2) 30 farmers with
      positive serum precipitating antibodies to Saccharopolyspora rectivirgula and/or
      Thermoactinomyces vulgaris without FLD (Ab(+)), and (3) 237 farmers without these
      antibodies (Ab(-)). Serum KL-6 concentrations in the FLD group were significantly
      higher than those in the Ab(+) and the Ab(-) groups (1,263 +/- 288 [SEM], 328 +/-
      57, and 207 +/- 6 U/mL, respectively, p < 0.001). Serum KL-6 concentrations in
      those with FLD were significantly higher than KL-6 concentrations from stored
      screening samples from the same individual when FLD was not diagnosed (1,263 +/-
      288 and 419 +/- 209 U/mL, respectively, p < 0.05). Serum KL-6 concentrations of
      the Ab(+) group were significantly higher than those of the Ab(-) group (p <
      0.001). In the Ab(+) group, farmers with high serum KL-6 concentrations had lower
      permeability coefficients than farmers with normal serum KL-6 concentrations (p <
      0.05). These results may suggest that subclinical FLD can be detected in farmers
      with high KL-6 concentrations and precipitating antibodies. CONCLUSION: Serum KL
      6 concentration can be a useful marker for assessing the activity of FLD and may
      be able to be used to detect subclinical disease.

PMID- 10936140
TI  - Soluble form of fas and fas ligand in BAL fluid from patients with pulmonary
      fibrosis and bronchiolitis obliterans organizing pneumonia.
AB  - STUDY OBJECTIVES: The Fas-Fas ligand (FasL) pathway is a representative system of
      apoptosis-signaling receptor molecules. We previously described that this pathway
      may play an important role in the pathogenesis of fibrosing lung diseases. In
      this study, we hypothesized that soluble form of Fas (sFas) and FasL (sFasL) may
      also be associated with this disorder. MEASUREMENTS AND RESULTS: We measured sFas
      and sFasL levels in BAL fluid (BALF) from patients with idiopathic pulmonary
      fibrosis (IPF), interstitial pneumonia associated with collagen vascular diseases
      (CVD-IP), and bronchiolitis obliterans organizing pneumonia (BOOP), using enzyme
      linked immunosorbent assay. BALF from all patients was obtained before
      prednisolone therapy. sFasL levels were relatively increased in IPF patients (p =
      0.084), and significantly increased in CVD-IP patients (p < 0.05) and BOOP
      patients (p < 0.05), compared with control subjects. BALF sFasL levels were
      elevated in the IPF or CVD-IP subgroups with an indication for prednisolone
      therapy, compared with those without an indication for therapy. The BALF sFasL
      level in IPF patients was correlated with the number of total cells and
      lymphocytes. The BALF sFasL level in BOOP patients was relatively or
      significantly correlated with the number of total cells or lymphocytes,
      respectively. The BALF sFas level was significantly increased in BOOP patients,
      but not in IPF or CVD-IP patients. CONCLUSIONS: We conclude that BALF sFasL
      levels may be associated with the accumulation of inflammatory cells and reflect
      the degree of lymphocyte alveolitis in IPF. The elevation of sFasL may be
      associated with the deterioration of IPF and CVD-IP. The elevation of the BALF
      sFas level may abrogate the cytotoxicity of FasL in BOOP patients, which may be
      associated with better prognosis of BOOP, compared with IPF or CVD-IP.

PMID- 10936141
TI  - Protocol weaning of mechanical ventilation in medical and surgical patients by
      respiratory care practitioners and nurses: effect on weaning time and incidence
      of ventilator-associated pneumonia.
AB  - STUDY OBJECTIVES: (1) To determine the effect of a single ventilator management
      protocol (VMP) used in medical and surgical ICUs on the duration of mechanical
      ventilation. (2) To determine the effect of a VMP on the incidence of ventilator
      associated pneumonia (VAP). DESIGN: Prospective, randomized, controlled study.
      SETTING: : University medical center. PATIENTS: Three hundred eighty-five
      patients receiving mechanical ventilation between June 1997 and May 1998.
      INTERVENTIONS: A respiratory care practitioner- and registered nurse-driven VMP.
      RESULTS: Intervention and control groups were comparable with respect to age,
      sex, severity of illness and injury, and duration of respiratory failure at the
      time of randomization. The duration of mechanical ventilation for patients was
      decreased from a median of 124 h for the control group to 68 h in the VMP group
      (p = 0.0001). Thirty-one total instances of VAP were noted. Twelve patients in
      the surgical control group had VAP, compared with 5 in the surgical VMP group (p
      = 0.061). The impact of the VMP on VAP frequency was less for medical patients.
      Mortality and ventilator discontinuation failure rates were similar between
      control and VMP groups. CONCLUSIONS: A VMP designed for multidisciplinary use was
      effective in reducing duration of mechanical ventilatory support without any
      adverse effects on patient outcome. The VMP was also associated with a decrease
      in incidence of VAP in trauma patients. These results, in conjunction with prior
      studies, suggest that VMPs are highly effective means of improving care, even in
      university ICUs.

PMID- 10936142
TI  - Reduction in tracheal lumen due to endotracheal intubation and its calculated
      clinical significance.
AB  - BACKGROUND: The flow in the human trachea is turbulent. Thus, the tracheal
      resistance (R) and the pressure gradient (DeltaP) required to maintain a given
      flow across the trachea is inversely related to its radius raised to the fifth
      power. If the caliber reduction ratio (X) after endotracheal intubation is
      calculated as X = radius of the endotracheal tube (rETT)/radius of the trachea
      (rT), then DeltaP and/or R will be increased by (1/X)(5). STUDY OBJECTIVES: To
      measure the actual ratio between rETT and rT following endotracheal intubation of
      pediatric patients with respiratory failure and to calculate the resulting
      increase in the tracheal R and DeltaP for a given inspiratory flow rate. DESIGN:
      Retrospective chart review. SETTING: Pediatric ICU in a tertiary-care teaching
      children's medical center. PATIENT ENROLLMENT: Twenty consecutive pediatric
      patients (mean [+/- SD] age, 6.4 +/- 7.2 years) whose tracheas had been intubated
      for various causes of respiratory failure, and who had received a CT scan, were
      included in our study. All patients received an endotracheal tube the size of
      which was derived from the following formula: (age in years/4) + 4. MEASUREMENTS
      AND MAIN RESULTS: rT and rETT were measured from CT scan sections at and around
      the level of the thoracic inlet, and the average values were used to calculate X.
      These values ranged from 0.33 to 0.65 (mean, 0. 55 +/- 0.8). The factor (1/X)(5)
      was calculated for each patient and then was multiplied by the known normal value
      for tracheal R for adolescents and adults (0.07 cm H(2)O/L/s) to obtain the value
      of R resulting from the artificial airway, (1/X)(5) x 0.07. Our results showed
      that tracheal R increased due to caliber reduction of the trachea after
      endotracheal intubation by 33.9 +/- 52.5-fold (range, 8.6- to 255.5-fold). In
      order to maintain an inspiratory flow of 1 L/s, the value of P for the intubated
      trachea would increase from 0. 07 cm H(2)O to a mean of 2.4 +/- 3.7 cm H(2)O
      (range, 0.6 to 18 cm H(2)O). In two of our patients, the rT/rETT ratios were <
      0.5 (0.33 and 0.44, respectively); this translated into a more significant
      increase in the calculated DeltaPs, 18 and 4.2 cm H(2)O, respectively.
      CONCLUSIONS: : The common value of X due to endotracheal intubation is between
      0.5 and 0.6, which in and of itself results in an increase in R across the
      intubated trachea up to 32-fold. The calculated increase in P as a result of this
      is between 2 and 3 cm H(2)O for adolescents or young adults. The addition of
      pressure support of at least 3 cm H(2)O during spontaneous ventilation via an
      endotracheal tube, which is common practice in pediatric critical care, should
      alleviate any respiratory distress emanating from the increased R. However, a
      value for X < 0.5, which was found in 10% of our patients (2 of 20 patients),
      results in a much higher calculated increase in the pressure gradient and,
      therefore, a higher level of pressure support is required to overcome this
      increase.

PMID- 10936143
TI  - Risks for developing critical illness with GI hemorrhage.
AB  - STUDY OBJECTIVES: To define risk factors, identifiable on initial presentation,
      that predict subsequent physiologic derangements that are consistent with
      critical illness in patients presenting to hospital with GI hemorrhage (GIH).
      DESIGN: Observational, cohort study. SETTING: Fourteen-bed medical ICU in a 300
      bed community teaching hospital. PATIENTS: One hundred ninety-three patients were
      studied during 199 separate hospital admissions for GIH. METHODS AMD
      MEASUREMENTS: Demographic and physiologic variables were extracted from the
      medical records of patients admitted with GIH. Comprehensive data, from after 2 h
      in the emergency department to the time of discharge or death, were used to
      determine whether patients met established ICU admission criteria. Physiologic
      and demographic data from the initial 2-h period were then compared for patients
      who subsequently met and for those who did not meet ICU admission criteria.
      Independent predictors of meeting ICU admission criteria were identified using
      multiple logistic regression analyses. Sensitivity and specificity associated
      with the combined use of these predictors were assessed. RESULTS: Thirty-four
      patients satisfied ICU admission criteria after the initial 2-h period in the
      emergency department. Sixty-five patients, including 29 of 34 patients who met
      ICU admission criteria, were actually admitted to the ICU. Among those who never
      fulfilled ICU admission criteria, the duration of hospital stay was longer for
      those admitted to the ICU than for those not admitted to ICU (6.6 +/- 0.6 days vs
      5.2 +/- 0.3 days; p = 0.04). The admission prothrombin time (international
      normalized ratio > 1.2), hypotension (systolic BP < 90 mm Hg), acute neurologic
      changes, and initial APACHE (acute physiology and chronic health evaluation) II
      score ( > or =15) were the best independent predictors for meeting the defined
      criteria for admission to ICU. The presence of one or more of these in the first
      2 h of presentation was associated with a sensitivity of 88% and specificity of
      74% for predicting subsequent critical instability. The area under the receiver
      operator characteristic curve for use of these four variables was 86% for
      predicting whether patients met ICU admission criteria. CONCLUSIONS: Many
      patients with GIH were admitted to the ICU who never met local criteria for
      admission, and these patients experienced a significantly longer length of
      hospital stay than other, similarly ill patients. Coagulopathy, hypotension,
      neurologic dysfunction, and a higher (> or = 15) APACHE II score in the first 2 h
      of hospitalization were the best independent predictors of the subsequent
      development of critical illness.

PMID- 10936144
TI  - Intracardiac thrombus in Behcet's disease: a systematic review.
AB  - BACKGROUND: Intracardiac thrombus formation is a rare but serious complication of
      Behcet's disease. We aimed to review the clinical and pathologic correlates of
      cardiac thrombus formation in the context of Behcet's disease. METHODS AND
      RESULTS: A comprehensive search of the medical literature was conducted using
      MEDLINE including bibliographies of all selected articles. Although the disease
      has a unique geographic distribution, being most common in the population of the
      ancient Silk Route, cases complicated by intracardiac thrombus have mostly
      originated from the Mediterranean basin and the Middle East. Young men appear to
      be most at risk, with the right heart the most frequent site of involvement. The
      first symptoms and signs of the disease frequently precede systemic organ
      manifestations. In those cases in which intracardiac thrombus occurs, it is
      apparent in more than half of cases on first recognition of the disease.
      CONCLUSION: A diagnosis of Behcet's disease should be considered if a patient
      presents with a mass in the right-sided cardiac chambers, even in the absence of
      the characteristic clinical features of the condition. This is particularly
      applicable if the patient is a young man from the Mediterranean basin or the
      Middle East.

PMID- 10936145
TI  - A pictorial review of coronary artery anatomy on spiral CT.
AB  - Coronary artery calcification quantification (scoring) has been done with
      electron beam CT (EBCT), but is now being done with spiral or helical CT. Many
      radiologists and cardiologists who do not have EBCT but do have access to spiral
      CT will now be able to do coronary artery calcification scoring, and will now
      need to know the spiral CT appearance of the coronary artery anatomy. This
      pictorial review will demonstrate the anatomy needed for coronary artery calcium
      scoring.

PMID- 10936146
TI  - Patients readmitted to ICUs* : a systematic review of risk factors and outcomes.
AB  - STUDY OBJECTIVE: To evaluate the causes, risk factors, and mortality rates
      associated with unexpected readmission to medical and surgical ICUs. DATA
      SOURCES: MEDLINE citation review of primary articles focusing on ICU readmission
      or ICU outcomes from January 1966 to June 1999, and contact with authors of
      primary studies. STUDY SELECTION: Eight primary studies of ICU readmission and
      eight multi-institutional ICU outcome studies that reported ICU readmission rates
      were included. DATA EXTRACTION: We abstracted data on the methodology and design
      of the primary studies, overall rates, causes, predictors, outcomes, and measures
      of quality of care associated with ICU readmission. DATA SYNTHESIS: The average
      ICU readmission rate of 7% (range, 4 to 14%) has remained relatively unchanged in
      both North America and Europe. Respiratory and cardiac conditions were the most
      common (30 to 70%) precipitating cause of ICU readmission. Patients readmitted to
      ICUs had average hospital stays at least twice as long as nonreadmitted patients.
      Hospital death rates were 2- to 10-times higher for readmitted patients than for
      those who survived an ICU admission and were never readmitted. Predictors of ICU
      readmission have been neither well studied nor reproducible. Unstable vital
      signs, especially respiratory and heart rate abnormalities, and the presence of
      poor pulmonary function at time of ICU discharge appear to be the most consistent
      predictors of ICU readmission. There were no consistent data supporting the use
      of readmission rates as a measure of quality of care. CONCLUSIONS: ICU
      readmission is associated with dramatically higher hospital mortality. Unstable
      vital signs at the time of ICU discharge are the most consistent predictor of ICU
      readmission. Further studies focusing on processes of ICU and hospital care are
      needed to determine if ICU readmission rates are a measure of quality of care.

PMID- 10936147
TI  - Proinflammatory cytokines.
AB  - STUDY OBJECTIVES: To review the concept of proinflammatory cytokines. DESIGN:
      Review of published literature. SETTING: Academic (university hospital). RESULTS:
      Cytokines are regulators of host responses to infection, immune responses,
      inflammation, and trauma. Some cytokines act to make disease worse
      (proinflammatory), whereas others serve to reduce inflammation and promote
      healing (anti-inflammatory). Attention also has focused on blocking cytokines,
      which are harmful to the host, particularly during overwhelming infection.
      Interleukin (IL)-1 and tumor necrosis factor (TNF) are proinflammatory cytokines,
      and when they are administered to humans, they produce fever, inflammation,
      tissue destruction, and, in some cases, shock and death. Reducing the biological
      activities of IL-1 and TNF is accomplished by several different, but highly
      specific, strategies, which involve neutralizing antibodies, soluble receptors,
      receptor antagonist, and inhibitors of proteases that convert inactive precursors
      to active, mature molecules. Blocking IL-1 or TNF has been highly successful in
      patients with rheumatoid arthritis, inflammatory bowel disease, or graft-vs-host
      disease but distinctly has not been successful in humans with sepsis. Agents such
      as TNF-neutralizing antibodies, soluble TNF receptors, and IL-1 receptor
      antagonist have been infused into > 10,000 patients in double-blind, placebo
      controlled trials. Although there has been a highly consistent small increase (2
      to 3%) in 28-day survival rates with anticytokine therapy, the effect has not
      been statistically significant. CONCLUSIONS: Anticytokine therapy should be able
      to "rescue" the patient whose condition continues to deteriorate in the face of
      considerable support efforts. Unfortunately, it remains difficult to identify
      those patients who would benefit from anticytokine therapy for septic shock.

PMID- 10936148
TI  - Combined lidocaine and salbutamol inhalation for airway anesthesia markedly
      protects against reflex bronchoconstriction.
AB  - BACKGROUND: Lidocaine inhalation, in subjects with bronchial hyperreactivity,
      attenuates evoked bronchoconstriction but also irritates airways. Whether
      salbutamol pretreatment can mitigate airway irritation and whether combined
      treatment offers more protection than treatment with either drug alone is
      unknown. Therefore, we evaluated the effects of the inhalation of lidocaine,
      salbutamol, lidocaine and salbutamol combined, and placebo on an inhalational
      histamine challenge. METHODS: Fifteen patients with mild asthma were selected by
      a screening procedure (ie, a provocative concentration of a substance [histamine
      aerosol of < 18 mg/mL] causing a 20% fall in FEV(1) [PC(20)]). On 4 different
      days after pretreatment with the inhalation of lidocaine (5 mg/kg), inhalation of
      salbutamol (1.5 mg), combined treatment, or placebo, the histamine challenge was
      repeated. RESULTS: The baseline FEV(1) after lidocaine inhalation but prior to
      the histamine challenge decreased by > 5% in 7 of 15 volunteers, with a mean (+/-
      SD) decrease from 3.82 +/- 0.90 to 3.54 +/- 0.86 L (p = 0.0054). The baseline
      PC(20) for histamine was 6.4 +/- 4.3 mg/mL. Both lidocaine and salbutamol
      inhalation significantly increased PC(20) more than twofold (14.9 +/- 13.7 and
      16.8 +/- 10.9 mg/mL, respectively; p = 0, 0007) at a lidocaine plasma
      concentration of 0.7 +/- 0.3 microg/mL. Combined treatment quadrupled the PC(20)
      to 29.7 +/- 20.3 mg/mL (vs lidocaine, p = 0.002; vs salbutamol, p = 0.003).
      CONCLUSIONS: Thus, histamine-evoked bronchoconstriction, as a model of reflex
      bronchoconstriction, can be significantly attenuated by salbutamol or lidocaine
      inhalation. However, lidocaine inhalation causes significant initial
      bronchoconstriction. The combined inhalation of salbutamol and lidocaine prevents
      the initial bronchoconstriction observed with lidocaine alone and offers even
      more protection to a histamine challenge than either lidocaine or salbutamol
      alone. Therefore, the combined inhalation of lidocaine and salbutamol can be
      recommended to mitigate bronchoconstriction when airway instrumentation is
      required.

PMID- 10936149
TI  - The heat is on: impact of endobronchial electrosurgery on the need for Nd-YAG
      laser photoresection.
AB  - STUDY OBJECTIVES: Advances in bronchoscopic electrosurgery have allowed its
      application in the outpatient setting in patients who otherwise would have
      required Nd-YAG laser photoresection (LPR) in the operating room. We intended to
      evaluate the impact of endobronchial electrosurgery (EBES) on the need for Nd-YAG
      LPR on patients with symptomatic airway lesions. DESIGN: Prospective
      observational case series. PARTICIPANTS: One hundred eighteen evaluations for LPR
      were performed. Forty-seven evaluations (40%) were considered to be amendable to
      EBES and were treated during the initial bronchoscopy. The remaining patients
      underwent LPR. SETTING: Outpatient bronchoscopy suite at the Cleveland Clinic
      Foundation, Cleveland, OH. RESULTS: Of the 47 procedures, 42 (89%) were
      successful in alleviating the obstruction, thus eliminating the need for LPR. No
      major complications were encountered. CONCLUSION: EBES can be performed safely in
      the outpatient setting and is an effective procedure in treating select
      endobronchial lesions. EBES eliminated the need for LPR in 36% of such procedures
      with a potential for significant time and cost savings.

PMID- 10936150
TI  - Safety of over-the-counter inhalers for asthma: report of the council on
      scientific affairs.
AB  - The occasional use of over-the-counter (OTC) epinephrine inhalers appears to be
      safe and effective when used according to labeled instruction by individuals with
      mild, intermittent asthma. However, gross misuse of these products can cause
      severe adverse reactions, including death. Limited survey data suggest that
      approximately 20% of individuals using OTC epinephrine inhalers have mild-to
      moderate persistent asthma. According to recent consensus guidelines, these
      individuals should be under a physician's care and receiving corticosteroid
      therapy. If these products continue to be marketed, labeling should be
      strengthened to better educate users about appropriate and inappropriate use of
      OTC epinephrine inhalers intended for patients with mild, intermittent asthma.

PMID- 10936152
TI  - Are the American College of Cardiology/American Heart Association guidelines for
      exercise testing for suspected coronary artery disease correct?
AB  - BACKGROUND: Recently published American College of Cardiology (ACC)/American
      Heart Association (AHA) guidelines state that patients with suspected coronary
      disease and an intermediate pretest probability are appropriate candidates for
      exercise ECG, while those with low or high pretest probability are not. METHODS:
      From 5,103 consecutive patients with symptoms of suspected coronary disease, we
      evaluated 872 patients who underwent coronary angiography following exercise ECG.
      Differences in test performance were determined using receiver operating
      characteristic curve area analysis. A score using age, gender, symptoms, and risk
      factors was used to classify patients into low, intermediate, and high pretest
      probability groups. RESULTS: When patients with inadequate exercise tests were
      excluded, overall sensitivity and specificity were 70% and 66%, respectively.
      Only the intermediate pretest probability group demonstrated significant
      incremental value: pretest vs posttest intermediate, 70 +/- 3 vs 79 +/- 3 (p <
      0.0001); low, 71 +/- 6 vs 76 +/- 7 (p = 0.39); and high, 69 +/- 8 vs 75 +/- 7 (p
      = 0.12). From the low- to the high-probability groups, there was a progressive
      increase in positive predictive value (21%, 62%, and 92%) and decrease in
      negative predictive value (94%, 72%, and 28%), respectively. The frequencies of
      abnormal exercise ECGs were lower in the unselected groups compared with the
      angiography groups (low, 13% vs 36%; intermediate, 22% vs 53%; high, 36% vs 63%).
      CONCLUSIONS: Based on the information added by exercise testing to clinical data,
      these results confirm the ACC/AHA guideline assignments for test selection.
      However, despite these guidelines, patients with a low pretest probability can be
      selected for exercise testing with the knowledge that a positive result is
      infrequent and a negative result carries a very high negative predictive value.
      Intermediate-probability patients on average carry a significant false-negative
      rate, suggesting that exercise ECG alone may not be a sufficient screening test
      in all intermediate-probability patients. Because of poor negative predictive
      value and a large percentage of negative tests, high-probability patients should
      undergo coronary angiography as the initial strategy, unless the goal of exercise
      testing is to assess prognosis.

PMID- 10936151
TI  - Pulmonary cryptococcosis in the immunocompetent host. Therapy with oral
      fluconazole: a report of four cases and a review of the literature.
AB  - Isolated pulmonary cryptococcosis (IPC) is an infrequently diagnosed infection,
      the management of which is not well defined. In past years, IPC traditionally has
      not been treated in the immunocompetent host, given its perceived benign and self
      limited course and the toxicity associated with amphotericin B. However, some
      patients manifest prominent and disabling symptoms, and infection occasionally
      may disseminate. Fluconazole is active against Cryptococcus neoformans, is easily
      administered, and has an excellent safety profile. We present four healthy hosts
      with IPC who were treated with oral fluconazole for 6 to 8 weeks. A review of the
      literature was conducted to identify other cases of IPC in healthy hosts who were
      also treated with fluconazole. Our results and the limited experience reported in
      the literature suggest that fluconazole may be an appropriate choice for the
      treatment of IPC in the immunocompetent host. Indications for treatment are not
      defined, but symptomatic patients, those with multiple nodules or extensive
      infiltrates on chest radiographs, and/or those testing positive for serum
      cryptococcal antigen might be potential candidates for therapy.

PMID- 10936153
TI  - Fever, pleuritic chest pain, and a lung mass in a 43-year-old man.

PMID- 10936154
TI  - Osmolar gap metabolic acidosis in a 60-year-old man treated for hypoxemic
      respiratory failure.

PMID- 10936155
TI  - Right atrial myxoma with extracardiac manifestations.
AB  - Right atrial myxoma is a rare intracardiac tumor that is often difficult to
      diagnose. Pulmonary embolism from tumor fragments originating from the tumor mass
      is a potentially fatal complication. Early diagnosis of cardiac myxoma is
      important since surgical treatment leads to resolution with low rates of
      recurrence and good long-term survival. The presence of a cardiac myxoma can be
      heralded by nonspecific constitutional symptoms as well as by disturbances in the
      clotting mechanism.

PMID- 10936156
TI  - Detection of occult thymoma during exercise thallium 201, technetium 99m
      tetrofosmin imaging for coronary artery disease.
AB  - Thallium (Tl) 201 and technetium (Tc) 99m tetrofosmin single-photon emission CT
      are routinely used in the evaluation of coronary artery disease. Mediastinal
      tumors demonstrate Tl 201 and Tc 99m tetrofosmin uptake. We report a 56-year-old
      man who developed chest pain after a previously successful angioplasty and stent
      of the left anterior descending coronary artery. He underwent a Tl 201, Tc 99m
      tetrofosmin exercise study. Abnormal mediastinal activity was visualized in both
      the Tl 201 and Tc 99m tetrofosmin images. Subsequently, the patient underwent
      resection of a stage II thymoma. Unanticipated focal extracardiac accumulation
      during myocardial scintiscanning should lead to further investigation to exclude
      mediastinal tumor.

PMID- 10936157
TI  - Metastatic ocular melanoma to the left ventricle inducing near-syncope attacks in
      an 84-year-old woman.
AB  - Cardiac tumors may represent mechanical causes for syncope by limiting left
      ventricular filling and/or by obstructing the left ventricular outflow tract.
      Malignant melanoma is known to metastasize to the myocardium or pericardium, but
      there are only a very limited number of reports describing endocardial
      involvement by the tumor. We describe herein an 84-year-old woman who presented
      with daily near-syncope episodes, 9 years after treatment for a choroidal
      melanoma. The echocardiography and the pathologic examination revealed a
      metastatic melanoma. This is the first reported case of an ocular melanoma
      metastasizing to the heart and presenting as a left ventricular intracavitary
      pedunculated mass.

PMID- 10936158
TI  - Platypnea-orthodeoxia syndrome related to an aortic aneurysm combined with an
      aneurysm of the atrial septum.
AB  - We report the case of a 71-year-old man bearing a severe right-to-left shunt
      through a patent foramen ovale in the absence of elevated right-sided heart or
      pulmonary artery pressures. He presented with platypnea-orthodeoxia syndrome, but
      he had no pulmonary or extracardiac diseases that are known to be associated with
      this syndrome. Chest radiography showed a bulky aneurysm of the thoracic aorta. A
      peripheral contrast transesophageal echocardiography demonstrated a large right
      to-left shunt through a patent foramen ovale. In addition, the atrial septum was
      severely deformed by an aneurysm including this patent foramen ovale. We
      hypothesized that the opening of the foramen ovale was the result of a mechanical
      deformation of the atrial septum by two contributing factors: the aneurysm of the
      thoracic aorta and the aneurysm of the septum itself.

PMID- 10936159
TI  - Contrast transesophageal echocardiography in the diagnosis and localization of
      diffuse pulmonary telangiectasias.
AB  - Pulmonary arteriovenous fistulas are rare, usually related to the Rendu-Osler
      Weber syndrome, and are detected by chest CT scan or pulmonary angiography. In a
      14-year-old boy without Rendu-Osler-Weber syndrome, but with clinical evidence of
      a right-to-left shunt, ancillary diagnostic studies were negative for pulmonary
      arteriovenous fistulas, and the final diagnosis was made by contrast
      transesophageal echocardiography. Saline echo-contrast medium injected
      peripherally was seen emerging from each pulmonary vein and filling the left
      chambers. These findings, in light of other negative test results, established
      the diagnosis of diffuse telangiectasias at the capillary level in both lungs.
      After 6 years of medical therapy, the patient remains cyanotic but functions
      well.

PMID- 10936160
TI  - Femoral venoarterial extracorporeal membrane oxygenation for severe
      reimplantation response after lung transplantation.
AB  - Severe pulmonary reimplantation response after lung transplantation is not very
      common, although the mortality can be high. We present a patient who developed an
      extremely severe reperfusion injury after bilateral lung transplantation. Because
      of severe hypoxia and hemodynamic instability, despite aggressive ventilator
      settings, venoarterial extracorporeal membrane oxygenation (ECMO) was instituted
      using the femoral approach at the bedside. During ECMO, the patient developed a
      thoracic wall hematoma that was treated with transfusion alone. After 50 h of
      ECMO, his chest radiograph had dramatically improved, his oxygen need had been
      reduced to 50%, and he was successfully weaned from ECMO. Two years later, he is
      doing extremely well. Therefore, institution of ECMO using the femoral approach
      can be performed safely at the bedside in the ICU, and can be lifesaving in the
      context of a very severe reimplantation response after lung transplantation.

PMID- 10936161
TI  - Acute renal failure, oxalosis, and vitamin C supplementation: a case report and
      review of the literature.
AB  - With the increased use of nonprescription vitamin supplementation, physicians
      involved in critical care must be aware of the potential complications of these
      medications. We report the case of a 31-year-old African-American man presenting
      to the emergency department with acute renal failure. He had previously been well
      and initially denied the use of any drugs except for vitamin C tablets obtained
      at a local health food store. This case report and review of the literature is
      utilized to illustrate the importance of historical data in patients presenting
      with acute renal failure to a critical care service.

PMID- 10936162
TI  - Morale and depression in patients treated surgically for intractable aspiration.

PMID- 10936163
TI  - Correction to the scientific record.

PMID- 10936164
TI  - Screening in hereditary hemorrhagic telangiectasia patients.

PMID- 10936165
TI  - Radiographic criteria in ARDS.

PMID- 10936166
TI  - Blood transfusion-always a minimum of two units?

PMID- 10936167
TI  - Role of inhaled budesonide in the treatment of tuberculous pyrexia.

PMID- 10936168
TI  - High-dose dexfenfluramine may cause alveolitis and pulmonary fibrosis in rats.

PMID- 10936169
TI  - Regulation of neurotransmitter release by metabotropic glutamate receptors.
AB  - The G protein-coupled metabotropic glutamate (mGlu) receptors are differentially
      localized at various synapses throughout the brain. Depending on the receptor
      subtype, they appear to be localized at presynaptic and/or postsynaptic sites,
      including glial as well as neuronal elements. The heterogeneous distribution of
      these receptors on glutamate and nonglutamate neurons/cells thus allows
      modulation of synaptic transmission by a number of different mechanisms.
      Electrophysiological studies have demonstrated that the activation of mGlu
      receptors can modulate the activity of Ca(2+) or K(+) channels, or interfere with
      release processes downstream of Ca(2+) entry, and consequently regulate neuronal
      synaptic activity. Such changes evoked by mGlu receptors can ultimately regulate
      transmitter release at both glutamatergic and nonglutamatergic synapses.
      Increasing neurochemical evidence has emerged, obtained from in vitro and in vivo
      studies, showing modulation of the release of a variety of transmitters by mGlu
      receptors. This review addresses the neurochemical evidence for mGlu receptor
      mediated regulation of neurotransmitters, such as excitatory and inhibitory amino
      acids, monoamines, and neuropeptides.

PMID- 10936170
TI  - Zebrafish genes for neuropeptide Y and peptide YY reveal origin by chromosome
      duplication from an ancestral gene linked to the homeobox cluster.
AB  - Neuropeptide Y (NPY) and peptide YY (PYY) are related 36-amino acid peptides. NPY
      is widely distributed in the nervous system and has several physiological roles.
      PYY serves as an intestinal hormone as well as a neuropeptide. We report here
      cloning of the npy and pyy genes in zebrafish (Danio rerio). NPY differs at only
      one to four amino acid positions from NPY in other jawed vertebrates. Zebrafish
      PYY differs at three positions from PYY from other fishes and at 10 positions
      from mammals. In situ hybridization showed that neurons containing NPY mRNA have
      a widespread distribution in the brain, particularly in the telencephalon, optic
      tectum, and rhombencephalon. PYY mRNA was found mainly in brainstem neurons, as
      reported previously for vertebrates as divergent as the rat and the lamprey,
      suggesting an essential role for PYY in these neurons. PYY mRNA was observed also
      in the telencephalon. These results were confirmed by immunocytochemistry. As in
      the human, the npy gene is located adjacent to homeobox (hox) gene cluster A
      (copy a in zebrafish), whereas the pyy gene is located close to hoxBa. This
      suggests that npy and pyy arose from a common ancestral gene in a chromosomal
      duplication event that also involved the hox gene clusters. As zebrafish has
      seven hox clusters, it is possible that additional NPY family genes exist or have
      existed. Also, the NPY receptor system seems to be more complex in zebrafish than
      in mammals, with at least two receptor genes without known mammalian orthologues.

PMID- 10936171
TI  - Taurine down-regulates basal and osmolarity-induced gene expression of its
      transporter, but not the gene expression of its biosynthetic enzymes, in
      astrocyte primary cultures.
AB  - Taurine content of astrocytes is primarily regulated by transport from the
      extracellular medium and endogenous biosynthesis from cysteine. We have
      investigated the gene expression of the taurine transporter (TauT) and the
      taurine biosynthetic enzymes, cysteine dioxygenase (CDO) and cysteine sulfinate
      decarboxylase (CSD), in astrocyte primary cultures in relationship to cell
      taurine content. TauT, CDO, and CSD mRNA levels were determined through
      quantitative RT-PCR. Cell taurine content was depleted by adapting the cells to a
      taurine-free chemically defined medium and increased by incubating the cells in
      the same medium containing exogenous taurine. With increased cell taurine content
      the level of TauT mRNA decreased, whereas the levels of CDO and CSD mRNA remained
      unchanged. In astrocytes exposed to a hyperosmotic medium the TauT mRNA level
      increased, whereas the CDO and CSD mRNA levels were not significantly altered.
      The osmolarity-induced up-regulation of TauT mRNA expression was fully prevented
      by increasing cell taurine content. Thus, the gene expression of the taurine
      transporter, but not that of the taurine biosynthetic enzymes, appears to be
      under the control of two antagonistic regulations, namely, a taurine-induced down
      regulation and an osmolarity-induced up-regulation.

PMID- 10936172
TI  - Astroglial trophic support and neuronal cell death: influence of cellular energy
      level on type of cell death induced by mitochondrial toxin in cultured rat
      cortical neurons.
AB  - Previous in vivo and in vitro analyses have shown that both necrosis and
      apoptosis are involved in neuronal cell death induced by energy impairment caused
      by mitochondrial dysfunction. However, little is known about the key factors that
      determine whether the cells undergo necrosis or apoptosis. In the present study,
      we analyzed neuronal cell death induced by 3-nitropropionic acid (3-NP), an
      irreversible inhibitor of mitochondrial complex II, in a primary culture system
      of rat cortical neurons. The neurons were maintained for a week in coculture with
      astroglial cells, and then they were treated with 3-NP in the presence or absence
      of astroglial cells. As judged from morphological (Hoechst 33258 staining) and
      biochemical (DNA fragmentation and caspase activation) analyses, the cortical
      neurons appeared to die through an apoptotic process after 3-NP treatment in the
      presence of astroglial cells. However, caspase inhibitors did not suppress the 3
      NP-induced cell death, suggesting the involvement of a caspase-independent
      pathway of 3-NP-induced neuronal cell death in the presence of astroglial cells.
      On the other hand, 3-NP induced necrotic cell death within 1 day in the absence
      of astroglial cells, following a rapid decrease in intracellular ATP level. These
      changes were attenuated by the presence of astroglial cells or the addition of
      astroglial conditioned medium. These results suggest that astroglial trophic
      support influences the alteration of the intracellular energy state in 3-NP
      treated neurons and consequently determines the type of neuronal cell death,
      apoptosis or necrosis.

PMID- 10936173
TI  - Activation of extracellular signal-regulated kinase (ERK) and Akt by human
      serotonin 5-HT(1B) receptors in transfected BE(2)-C neuroblastoma cells is
      inhibited by RGS4.
AB  - Regulator of G protein signaling (RGS) proteins are GTPase-activating proteins
      for heterotrimeric G proteins. One of the best-studied RGS proteins, RGS4,
      accelerates the rate of GTP hydrolysis by all G(i) and G(q) alpha subunits yet
      has been shown to exhibit receptor selectivity. Although RGS4 is expressed
      primarily in brain, its effect on modulating the activity of serotonergic
      receptors has not yet been reported. In the present study, transfected BE(2)-C
      human neuroblastoma cells expressing human 5-HT(1B) receptors were used to
      demonstrate that RGS4 can inhibit the coupling of 5-HT(1B) receptors to cellular
      signals. Serotonin and sumatriptan were found to stimulate activation of
      extracellular signal-regulated kinase. This activation was attenuated, but not
      completely inhibited, by RGS4. Similar inhibition by RGS4 of the protein kinase
      Akt was also observed. As RGS4 is expressed at high levels in brain, these
      results suggest that it may play a role in regulating serotonergic pathways.

PMID- 10936174
TI  - Overexpression of Cu,Zn superoxide dismutase attenuates oxidative inhibition of
      astrocyte glutamate uptake.
AB  - Glutamate neurotoxicity in brain is normally prevented by rapid uptake of
      glutamate by astrocytes. Increased expression of Cu,Zn superoxide dismutase
      (SOD1) can increase resistance to cerebral ischemia and other oxidative insults,
      but the cellular mechanisms by which this occurs are not well established. Here
      we examine whether increased SOD1 expression can attenuate inhibition of
      astrocyte glutamate uptake by reactive oxygen species. Primary cortical astrocyte
      cultures were prepared from transgenic mice that overexpress human SOD1 and from
      nontransgenic littermate controls. Glutamate uptake was assessed after exposure
      of these cultures to xanthine oxidase plus hypoxanthine, an extracellular
      superoxide generating system, or to menadione, which generates superoxide in the
      cytosol. These treatments produced dose-dependent reductions in astrocyte
      glutamate uptake, and the reductions were significantly attenuated in the SOD1
      transgenic astrocytes. A specific effect of reactive oxygen species on glutamate
      transporters was suggested by the much smaller inhibitory effects of xanthine
      oxidase/hypoxanthine and menadione on GABA uptake than on glutamate uptake. These
      findings suggest that the cerebroprotective effects of increased SOD1 expression
      during cerebral ischemia-reperfusion could be mediated in part by astrocyte
      glutamate transport.

PMID- 10936175
TI  - Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by
      antioxidants through suppression of cisplatin-mediated accumulation of p53 but
      not of Fas/Fas ligand.
AB  - Peripheral neuropathy following cisplatin treatment is a major limiting factor in
      cisplatin chemotherapy of cancer patients. We investigated the pathomechanism
      underlying cisplatin neuropathy using a mouse dorsal root ganglion neuron
      neuroblastoma hybrid cell line (N18D3) developed in our laboratory. DNA
      fragmentation, a characteristic feature of apoptosis, was induced in hybrid
      neurons following treatment with cisplatin. Accumulation of p53, Fas, and Fas
      ligand (Fas-L) was also demonstrated in these neurons. Preincubation with N
      acetylcysteine (NAC), a precursor of glutathione, blocked cisplatin-induced
      apoptosis completely, whereas Trolox, a vitamin E analogue, blocked it partially.
      Cisplatin-induced p53 accumulation was suppressed by NAC treatment, whereas p53
      accumulation was retarded by Trolox treatment. In contrast, neither NAC nor
      Trolox showed any inhibitory effect on cisplatin-induced Fas/Fas-L accumulation.
      These results suggest that the neuroprotective effects of antioxidants against
      cisplatin-induced neurotoxicity in hybrid neurons are mediated mainly through the
      inhibition of p53 accumulation but not of Fas/Fas-L accumulation by these
      antioxidants.

PMID- 10936176
TI  - Alcohol exposure alters the expression pattern of neural cell adhesion molecules
      during brain development.
AB  - Neural cell adhesion molecules (NCAMs) play critical roles during development of
      the nervous system. The aim of this study is to investigate the possible effect
      of ethanol exposure on the pattern of expression and sialylation of NCAM isoforms
      during postnatal rat brain development because alterations in NCAM content and
      distribution have been associated with defects in cell migration, synapse
      formation, and memory consolidation, and deficits in these processes have been
      observed after in utero alcohol exposure. The expression of NCAM isoforms in the
      developing cerebral cortex of pups from control and alcohol-fed mothers was
      assessed by western blotting, ribonuclease protection assay, and
      immunocytochemistry. The highly sialylated form of NCAM [polysialic acid (PSA)
      NCAM] is mainly expressed during the neonatal period and then is down-regulated
      in parallel with the appearance of NCAM 180 and NCAM 140. Ethanol exposure
      increases PSA-NCAM levels during the neonatal period, delays the loss of PSA
      NCAM, decreases the amount of NCAM 180 and NCAM 140 isoforms, and reduces
      sialyltransferase activity during postnatal brain development. Neuraminidase
      treatment of ethanol-exposed neonatal brains leads to more intense band
      degradation products, suggesting a higher content of NCAM polypeptides carrying
      PSA in these samples. However, NCAM mRNA levels are not changed by ethanol.
      Immunocytochemical analysis demonstrates that ethanol triggers an increase in PSA
      NCAM immunolabeling in the cytoplasm of astroglial cells, accompanied by a
      decrease in immunogold particles over the plasma membrane. These findings
      indicate that ethanol exposure during brain development alters the pattern of
      NCAM expression and suggest that modification of NCAM could affect neuronal-glial
      interactions that might contribute to the brain defects observed after in utero
      alcohol exposure.

PMID- 10936177
TI  - Extracellular ATP triggers tumor necrosis factor-alpha release from rat
      microglia.
AB  - Brain microglia are a major source of inflammatory cytokines, such as tumor
      necrosis factor-alpha (TNF-alpha), which have been implicated in the progression
      of neurodegenerative diseases. Recently, microglia were revealed to be highly
      responsive to ATP, which is released from nerve terminals, activated immune
      cells, or damaged cells. It is not clear, however, whether released ATP can
      regulate TNF-alpha secretion from microglia. Here we demonstrate that ATP
      potently stimulates TNF-alpha release, resulting from TNF-alpha mRNA expression
      in rat cultured brain microglia. The TNF-alpha release was maximally elicited by
      1 mM ATP and also induced by a P2X(7) receptor-selective agonist, 2'- and 3'-O-(4
      benzoylbenzoyl)adenosine 5'-triphosphate, suggesting the involvement of P2X(7)
      receptor. ATP-induced TNF-alpha release was Ca(2+)-dependent, and a sustained
      Ca(2+) influx correlated with the TNF-alpha release in ATP-stimulated microglia.
      ATP-induced TNF-alpha release was inhibited by PD 098059, an inhibitor of
      extracellular signal-regulated protein kinase (ERK) kinase 1 (MEK1), which
      activates ERK, and also by SB 203580, an inhibitor of p38 mitogen-activated
      protein kinase. ATP rapidly activated both ERK and p38 even in the absence of
      extracellular Ca(2+). These results indicate that extracellular ATP triggers TNF
      alpha release in rat microglia via a P2 receptor, likely to be the P2X(7)
      subtype, by a mechanism that is dependent on both the sustained Ca(2+) influx and
      ERK/p38 cascade, regulated independently of Ca(2+) influx.

PMID- 10936178
TI  - Oncostatin M-mediated growth inhibition of human glioblastoma cells does not
      depend on stat3 or on mitogen-activated protein kinase activation.
AB  - Oncostatin M (OSM) and other members of the interleukin-6 cytokines, like ciliary
      neurotrophic factor and leukemia inhibitory factor, can induce differentiation of
      glial cells. We have recently described that OSM inhibited the growth of human
      glioma cells in vitro and induced a cell morphology resembling that of mature
      astrocytes. Using the glioblastoma cell line 86HG39, we demonstrated that
      treatment of the glioma cells with OSM also leads to a differentiation of the
      malignant glioma cells as judged by a strong increase in glial fibrillary acidic
      protein expression. The differentiation and the growth inhibition were not
      significantly blocked by expression of a dominant-negative (dn) signal transducer
      and activator of transcription (Stat) 3 protein. OSM exerted a reduction in DNA
      synthesis even in the presence of a high expression level of dnStat3. Moreover,
      inhibition of the ras-raf-mitogen-activated protein kinase (MAPK) pathway by the
      MAPK kinase 1 inhibitor PD98059 resulted in a synergistic enhancement of the OSM
      effect, indicating that the activation of this pathway counteracts the activity
      of the cytokine.

PMID- 10936179
TI  - 2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4
      methylenedioxymethamphetamine-induced serotonin neurotoxicity.
AB  - Neurotoxicity induced by different substituted amphetamines has been associated
      with the exhaustion of intracellular energy stores. Accordingly, we examined the
      influence of 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glucose uptake
      and metabolism, and nicotinamide, an agent that improves energy metabolism, on 3,
      4-methylenedioxymethamphetamine (MDMA)-induced 5-hydroxytryptamine (5-HT;
      serotonin) deficits. Administration of MDMA (15 mg/kg i.p.) produced a
      significant hyperthermia, whereas 2-DG caused a profound hypothermia that lasted
      throughout the experiment. When MDMA was given to 2-DG-treated rats, an immediate
      but transient hyperthermia occurred and was followed by a return to hypothermia.
      2-DG had no effect on 5-HT concentrations in the frontal cortex, hippocampus, and
      striatum but prevented the neurotoxicity induced by MDMA. When rats were injected
      with 2-DG/MDMA and were warmed to prevent hypothermia, the protection afforded by
      2-DG was abolished. Nicotinamide had no effect on body temperature of the rats,
      and the hyperthermia induced by the nicotinamide/MDMA treatment was similar to
      that of the saline/MDMA-treated rats. However, the long-term 5-HT deficits
      induced by MDMA were potentiated by nicotinamide in all the brain regions
      examined. Finally, no change on ATP concentrations in the frontal cortex,
      hippocampus, and striatum was observed up to 3 h after a single dose of MDMA.
      These results suggest that an altered energy metabolism is not the main cause of
      the neurotoxic effects induced by MDMA.

PMID- 10936180
TI  - Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived
      neurotrophic factor gives rise to fully differentiated, neurotrophic factor
      dependent, human neuron-like cells.
AB  - A rapid and simple procedure is presented to obtain nearly pure populations of
      human neuron-like cells from the SH-SY5Y neuroblastoma cell line. Sequential
      exposure of SH-SY5Y cells to retinoic acid and brain-derived neurotrophic factor
      in serum-free medium yields homogeneous populations of cells with neuronal
      morphology, avoiding the presence of other neural crest derivatives that would
      normally arise from those cells. Cells are withdrawn from the cell cycle, as
      shown by 5-bromo-2'-deoxyuridine uptake and retinoblastoma hypophosphorylation.
      Cell survival is dependent on the continuous presence of brain-derived
      neurotrophic factor, and removal of this neurotrophin causes apoptotic cell death
      accompanied by an attempt to reenter the cell cycle. Differentiated cells express
      neuronal markers, including neurofilaments, neuron-specific enolase, and growth
      associated protein-43 as well as neuronal polarity markers such as tau and
      microtubule-associated protein 2. Moreover, differentiated cultures do not
      contain glial cells, as could be evidenced after the negative staining for glial
      fibrillary acidic protein. In conclusion, the protocol presented herein yields
      homogeneous populations of human neuronal differentiated cells that present many
      of the characteristics of primary cultures of neurons. This model may be useful
      to perform large-scale biochemical and molecular studies due to its
      susceptibility to genetic manipulation and the availability of an unlimited
      amount of cells.

PMID- 10936182
TI  - Different subtypes of tachykinin NK(1) receptor binding sites are present in the
      rat brain.
AB  - (2-[(125)I]iodohistidyl(1))Neurokinin A ([(125)I]NKA), which labels "septide
      sensitive" but not classic NK(1) binding sites in peripheral tissues, was used to
      determine whether septide-sensitive binding sites are also present in the rat
      brain. Binding studies were performed in the presence of SR 48968 (NK(2)
      antagonist) and senktide (NK(3) agonist) because [(125)I]NKA also labels
      peripheral NK(2) binding sites and, as shown in this study, central NK(3) binding
      sites. [(125)I]NKA was found to label not only septide-sensitive binding sites
      but also a new subtype of NK(1) binding site distinct from classic NK(1) binding
      sites. Both subtypes of [(125)I]NKA binding sites were sensitive to tachykinin
      NK(1) antagonists and agonists but also to the endogenous tachykinins NKA,
      neuropeptide K (NPK), and neuropeptide gamma (NPgamma). However, compounds of the
      septide family such as substance P(6-11) [SP(6-11)] and propionyl
      [Met(O(2))(11)]SP(7-11) and some NK(1) antagonists, GR 82334, RP 67580, and CP
      96345, had a much lower affinity for the new NK(1)-sensitive sites than for the
      septide-sensitive sites. The hypothalamus and colliculi possess only this new
      subtype of NK(1) site, whereas both types of [(125)I]NKA binding sites were found
      in the amygdala and some other brain structures. These results not only explain
      the central effects of septide or SP(6-11), but also those of NKA, NPK, and
      NPgamma, which can be selectively blocked by NK(1) receptor antagonists.

PMID- 10936181
TI  - Identification of multiple forms of membrane-associated neutral sphingomyelinase
      in bovine brain.
AB  - Many different stimuli such as bioactive agents and environmental stresses are
      known to cause the activation of sphingomyelinase (SMase), which hydrolyzes
      sphingomyelin to generate ceramide as a second messenger playing a key role in
      differentiation and apoptosis in various cell types. Here we identified multiple
      forms of the membrane-associated neutral SMase (N-mSMase) activity in bovine
      brain. They could be classified into two groups according to extracting agents:
      group T-mSMase, extracted with 0.2% Triton X-100, and group S-mSMase, extracted
      with 0.5 M (NH(4))(2)SO(4). Group T-mSMase: alpha, beta, gamma, and delta, which
      were extensively purified from 40,000-g pellets of bovine brain homogenates by
      3,150-, 5,275-, 1,665-, and 2,556-fold over the membrane extracts, respectively,
      by sequential use of several column chromatographies. On the other hand, S-mSMase
      was eluted as two active peaks of S-mSMase epsilon and zeta in a phenyl-5PW
      hydrophobic HPLC column and further purified by 1,119- and 976-fold over 40,000-g
      pellets of the homogenates, respectively. These highly purified N-mSMase enzyme
      preparations migrated as several bands on sodium dodecyl sulfate-polyacrylamide
      gel electrophoresis and showed many different features in biochemical properties
      such as pH dependence, Mg(2+) requirements, and effects of detergents. Taken
      together, our data strongly suggest that mammalian brain N-mSMase may exist as
      multiple forms different in both its chromatographic profiles and biochemical
      properties.

PMID- 10936183
TI  - Lactate prevents the alterations in tissue amino acids, decline in ATP, and cell
      damage due to aglycemia in retina.
AB  - Under conditions of energy impairment, CNS tissue can utilize substrates other
      than glucose to maintain energy metabolism. Retinas produce large amounts of
      lactate, although it has not been shown that lactate can be utilized by retina to
      prevent the cell damage associated with hypoglycemia. To investigate this,
      intact, isolated retinas were subjected to aglycemic conditions in the presence
      or absence of 20 mM lactate. Retinas incubated in the absence of glucose for 60
      min showed a threefold elevation in tissue aspartate and 60% decreases in tissue
      glutamate and glutamine, demonstrating a mobilization of carbon from glutamine
      and glutamate to the tricarboxylic acid cycle. Lactate prevented these changes in
      tissue amino acids, indicating metabolism of lactate with sparing of tissue
      glutamate and glutamine. Tissue ATP was 20 and 66% of control values with zero
      glucose or zero glucose plus lactate, respectively. Consistent with previous
      findings, incubation of retinas in the absence of glucose caused acute swelling
      of retinal neurons and release of GABA into the medium at 60 min. These acute
      toxic affects caused by the absence of glucose were completely prevented by the
      presence of lactate. At 24 h of recovery following 60 min of zero glucose, many
      pyknotic profiles were observed and lactate dehydrogenase (LDH) release into the
      medium was elevated sevenfold, indicating the extent of cell death. In contrast,
      no elevation in LDH was found and histology appeared normal in retinas exposed to
      zero glucose in the presence of lactate. alpha-Cyano-4-hydroxy cinnamate (4-CIN;
      0.5 mM), an inhibitor of the monocarboxylic acid transporter and mitochondrial
      pyruvate carrier, blocked the ability of lactate to maintain ATP and protect
      retinas from aglycemia but had no effect on ATP or toxicity per se. Derangements
      in tissue aspartate, glutamate, and glutamine, which were prevented by lactate
      during zero glucose incubation, were again observed with lactate plus zero
      glucose in the presence of 4-CIN. However, 0.5 mM 4-CIN alone in the presence of
      glucose produced similar increases in aspartate and decreases in glutamate and
      glutamine as observed with zero glucose while having only modest inhibitory
      effects on [U-(14)C]lactate uptake, suggesting the mitochondrial pyruvate carrier
      as the main site of action. The above findings show that lactate is readily
      utilized by the chick retina during glucose deprivation to prevent derangements
      in tissue amino acids and ATP and retinal neuronal cell death.

PMID- 10936184
TI  - Chronic ethanol exposure attenuates the anti-apoptotic effect of NMDA in
      cerebellar granule neurons.
AB  - Ethanol, added to primary cultures of cerebellar granule neurons simultaneously
      with NMDA, was previously shown to inhibit the anti-apoptotic effect of NMDA. The
      in vitro anti-apoptotic effect of NMDA is believed to mimic in vivo protection
      against apoptosis afforded by innervation of developing cerebellar granule
      neurons by glutamatergic mossy fibers. Therefore, the results suggested that the
      presence of ethanol in the brain at a critical period of development would
      promote apoptosis. In the present studies, we examined the effect of chronic
      ethanol exposure on the anti-apoptotic action of NMDA in cerebellar granule
      neurons. The neurons were treated with ethanol in vitro for 1-3 days in the
      absence of NMDA. Even after ethanol was removed from the culture medium, as
      ascertained by gas chromatography, the protective effect of added NMDA was
      significantly attenuated. The decreased anti-apoptotic effect of NMDA was
      associated with a change in the properties of the NMDA receptor, as indicated by
      a decrease in ligand binding, decreased expression of NMDA receptor subunit
      proteins, and decreased functional responses including stimulation of increases
      in intracellular Ca(2+) and induction of brain-derived neurotrophic factor
      expression. The latter effect may directly underlie the attenuated protective
      effect of NMDA in these neurons. The results suggest that ethanol exposure during
      development can have long-lasting effects on neuronal survival. The change in the
      NMDA receptor caused by chronic ethanol treatment may contribute to the loss of
      cerebellar granule neurons that is observed in animals and humans exposed to
      ethanol during gestation.

PMID- 10936185
TI  - Enzymatic degradation protects neurons from glutamate excitotoxicity.
AB  - Several enzymes with the capacity to degrade glutamate have been suggested as
      possible neuroprotectants. We initially evaluated the kinetic properties of
      glutamate pyruvate transaminase (GPT; also known as alanine aminotransferase),
      glutamine synthetase, and glutamate dehydrogenase under physiologic conditions to
      degrade neurotoxic concentrations of glutamate. Although all three enzymes
      initially degraded glutamate rapidly, only GPT was able to reduce toxic (500
      microM) levels of glutamate into the physiologic (<20 microM) range. Primary
      cultures of fetal murine cortical neurons were subjected to paradigms of either
      exogenous or endogenous glutamate toxicity to evaluate the neuroprotective value
      of GPT. Neuronal survival after exposure to added glutamate ranging from 100 to
      500 microM was improved significantly in the presence of GPT (> or =1 U/ml).
      Cultures were also exposed to the glutamate transporter inhibitor L-trans
      pyrrolidine-2,4-dicarboxylate (PDC), which produces neuronal injury by elevating
      extracellular glutamate. GPT significantly reduced the toxicity of PDC. This
      reduction was associated with a reduction in the PDC-dependent rise in the medium
      concentration of glutamate. These results suggest that enzymatic degradation of
      glutamate by GPT can be an alternative to glutamate receptor blockade as a
      strategy to protect neurons from excitotoxic injury.

PMID- 10936186
TI  - Phospholipase D2 activity suppresses hydrogen peroxide-induced apoptosis in PC12
      cells.
AB  - Phospholipase D (PLD) plays an important role as an effector in the membrane
      lipid-mediated signal transduction. However, the precise physiological functions
      of PLD are not yet well understood. In this study, we examined the role of PLD
      activity in hydrogen peroxide (H(2)O(2))-induced apoptosis in rat
      pheochromocytoma (PC12) cells. Treatment of PC12 cells with H(2)O(2) resulted in
      induction of apoptosis in these cells, which is accompanied by the activation of
      PLD. This H(2)O(2)-induced apoptosis was enhanced remarkably when phosphatidic
      acid production by PLD was selectively inhibited by pretreating the PC12 cells
      with 1-butanol. Expression of PLD2, but not of PLD1, correlated with increased
      H(2)O(2)-induced PLD activity in a concentration- and time-dependent manner.
      Concomitant with PLD activation, the PLD2 activity suppressed H(2)O(2)-induced
      apoptosis in PC12 cells. Expression of PLD2 lipase-inactive mutant (K758R) had no
      effect on either PLD activity or apoptosis. PLD2 activity also suppressed
      H(2)O(2)-induced cleavage and activation of caspase-3. Taken together, the
      results suggest that PLD2 activity is specifically up-regulated by H(2)O(2) in
      PC12 cells and that it plays a suppressive role in H(2)O(2)-induced apoptosis.

PMID- 10936187
TI  - Phagocytic clearance of apoptotic neurons by Microglia/Brain macrophages in
      vitro: involvement of lectin-, integrin-, and phosphatidylserine-mediated
      recognition.
AB  - Microglia, the tissue macrophages of the brain, play a crucial role in
      recognition and phagocytic removal of apoptotic neurons. The microglial receptors
      for recognition of apoptotic neurons are not yet characterized. Here we
      established a co-culture model of primary microglia and cerebellar granule
      neurons to examine the receptor systems involved in recognition/uptake of
      apoptotic neurons. Treatment with 100 microM S-nitrosocysteine induced apoptosis
      of cerebellar neurons as indicated by nuclear condensation and phosphatidylserine
      exposure to the exoplasmic leaflet of the plasma membrane. Microglial cells were
      added to neurons 2 h after apoptosis induction and co-cultured for 6 h in the
      presence of ligands that inhibit recognition by binding to respective receptors.
      Binding/phagocytosis was determined after combined 4', 6-diamidino-2
      phenylindole/propidium iodide (for apoptotic/necrotic neurons) and lectin
      staining (for microglia). Uptake of apoptotic neurons was reduced by N
      acetylglucosamine or galactose, suggesting that recognition involves
      asialoglycoprotein-like lectins. Furthermore, the inhibition of microglial
      binding/uptake of apoptotic neurons by RGDS peptide suggests a role of microglial
      vitronectin receptor. As microglia selectively bind lipid vesicles enriched in
      phosphatidylserine and O-phospho-L-serine interfered with the uptake of apoptotic
      neurons, an involvement of phosphatidylserine receptor is rather likely.
      Apoptotic neurons do not release soluble signals that serve to attract or
      activate microglia. Collectively, these results suggest that apoptotic neurons
      generate a complex surface signal recognized by different receptor systems on
      microglia.

PMID- 10936188
TI  - Differential expression of D(1A) and D(1B) dopamine receptor mRNAs in the
      developing avian retina.
AB  - In the chick retina, the D1 dopaminergic system differentiates very early, as
      shown by receptor-mediated increases in intracellular cyclic AMP concentration
      and the presence of [(3)H]SCH23390-specific binding sites. Here, we
      characterized, by RT-PCR, the expression of defined D1 receptor subtypes D(1A),
      D(1B), and D(1D) during the development of the chick retina. Total RNA was
      extracted from retinas of 6-day-old embryos (E6) to 1-day-old hatched chickens
      and reverse-transcribed. The resulting cDNA was amplified using D(1A)-, D(1B)-,
      or D(1D)-specific primers, and the PCR-amplified products were analyzed by
      electrophoresis. The fragment corresponding to D(1A) receptor was detected in
      developing retina as early as E7, whereas the fragment corresponding to D(1B) was
      observed starting around E10. No PCR product corresponding to D(1D) was observed
      in the retina, although it was detected in chick brain. As synaptogenesis in
      chick retina begins after E11 and [(3)H]SCH 23390 D1 binding sites increase after
      this stage, the present results show that expression of D(1B) receptor increases
      during synaptogenesis, whereas D(1A) is the receptor subtype associated with the
      D1-like actions of dopamine early in retina development.

PMID- 10936189
TI  - The GLT-1 and GLAST glutamate transporters are expressed on morphologically
      distinct astrocytes and regulated by neuronal activity in primary hippocampal
      cocultures.
AB  - The GLT-1 and GLAST astroglial transporters are the glutamate transporters mainly
      involved in maintaining physiological extracellular glutamate concentrations.
      Defects in neurotransmitter glutamate transport may represent an important
      component of glutamate-induced neurodegenerative disorders (such as amyotrophic
      lateral sclerosis) and CNS insults (ischemia and epilepsy). We characterized the
      protein expression of GLT-1 and GLAST in primary astrocyte-neuron cocultures
      derived from rat hippocampal tissues during neuron differentiation/maturation.
      GLT-1 and GLAST are expressed by morphologically distinct glial fibrillary acidic
      protein-positive astrocytes, and their expression correlates with the status of
      neuron differentiation/maturation and activity. Up-regulation of the transporters
      paralleled the content of the synaptophysin synaptic vesicle marker p38, and down
      regulation was a consequence of glutamate-induced neuronal death or the reduction
      of synaptic activity. Finally, soluble factors in neuronal-conditioned media
      prevented the down-regulation of the GLT-1 and GLAST proteins. Although other
      mechanisms may participate in regulating GLT-1 and GLAST in the CNS, our data
      indicate that soluble factors dependent on neuronal activity play a major
      regulating role in hippocampal cocultures.

PMID- 10936190
TI  - Neuron-specific phosphorylation of Alzheimer's beta-amyloid precursor protein by
      cyclin-dependent kinase 5.
AB  - The mature form of Alzheimer's beta-amyloid precursor protein (APP) is
      phosphorylated specifically at Thr(668) in neurons. In mature neurons,
      phosphorylated APP is detected in neurites, with dephosphorylated APP being found
      mostly in the cell body. In vitro, active cyclin-dependent kinase 5 (Cdk5)
      phosphorylated the cytoplasmic domain of APP at Thr(668). Treatment of mature
      neurons with an antisense oligonucleotide to Cdk5 suppressed Cdk5 expression and
      significantly diminished the level of phosphorylated APP. The expression of APP
      was unaffected in antisense-treated neurons. These results indicate that in
      neurons APP is phosphorylated by Cdk5, and that this may play a role in its
      localization.

PMID- 10936191
TI  - Facilitatory roles of novel compounds designed from cyclopentenone prostaglandins
      on neurite outgrowth-promoting activities of nerve growth factor.
AB  - Cyclopentenone prostaglandins (PGs) are known to arrest the cell cycle at the
      G(1) phase in vitro and to suppress tumor growth in vivo. However, their effects
      on neurons are unclear. Here, we report that some cyclopentenone PGs function as
      neurite outgrowth-promoting factors. They promoted neurite outgrowth from PC12
      cells and from dorsal root ganglion explants but only in the presence of nerve
      growth factor (NGF). We refer to these PGs as neurite outgrowth-promoting PGs
      (NEPPs). Through study of the structure-function relationship of NEPP1-10 and
      related compounds, we found that the cross-conjugated dienone moiety of NEPPs was
      essential for promoting neurite outgrowth, and NEPP10 was concluded to be the
      best candidate for drug development. We also investigated the intracellular
      mechanism of the promotion by NEPPs and obtained evidence that immunoglobulin
      heavy chain binding protein/glucose-regulated protein 78 (BiP/GRP78) plays a role
      in the promotion, based on the following observations: Antisense nucleotides for
      BiP/GRP78 gene blocked the promotion of neurite outgrowth; BiP/GRP78 protein
      level increased in response to NEPPs; and overexpression of BiP/GRP78 protein by
      adenoviral gene transfer promoted the neurite outgrowth by NGF.

PMID- 10936192
TI  - Overexpression of HuD, but not of its truncated form HuD I+II, promotes GAP-43
      gene expression and neurite outgrowth in PC12 cells in the absence of nerve
      growth factor.
AB  - We have previously shown that the RNA-binding protein HuD binds to a regulatory
      element in the growth-associated protein (GAP)-43 mRNA and that this interaction
      involves its first two RNA recognition motifs (RRMs). In this study, we
      investigated the functional significance of this interaction by overexpression of
      human HuD protein (pcHuD) or its truncated form lacking the third RRM (pcHuD
      I+II) in PC12 cells. Morphological analysis revealed that pcHuD cells extended
      short neurites containing GAP-43-positive growth cones in the absence of nerve
      growth factor (NGF). These processes also contained tubulin and F-actin filaments
      but were not stained with antibodies against neurofilament M protein. In
      correlation with this phenotype, pcHuD cells contained higher levels of GAP-43
      without changes in levels of other NGF-induced proteins, such as SNAP-25 and tau.
      In mRNA decay studies, HuD stabilized the GAP-43 mRNA, whereas HuD I+II did not
      have any effect either on GAP-43 mRNA stability or on the levels of GAP-43
      protein. Likewise, pcHuD I+II cells showed no spontaneous neurite outgrowth and
      deficient outgrowth in response to NGF. Our results indicate that HuD is
      sufficient to increase GAP-43 gene expression and neurite outgrowth in the
      absence of NGF and that the third RRM in the protein is critical for this
      function.

PMID- 10936193
TI  - Glutamate receptor subunit delta2 is highly expressed in a novel population of
      glial-like cells in rat pineal glands in culture.
AB  - The mammalian pineal gland uses L-glutamate as an intercellular chemical
      transmitter to regulate negatively melatonin synthesis. To receive glutamate
      signals, pinealocytes express at least three kinds of glutamate receptors:
      metabotropic receptor types 3 and 5 and an ionotropic receptor, GluR1. In this
      study, we examined whether or not the fourth class of ionotropic receptor, delta,
      which is known for its nondefinitive molecular function and its unique expression
      pattern in brain, is expressed in pineal gland. RT-PCR analyses with specific
      probes indicated the expression of mRNA of delta2 but not that of delta1 in
      pineal gland and cultured pineal cells. Western blotting analysis with polyclonal
      antibodies specific to the carboxyl-terminal region of the delta2 receptor
      recognized a single 110-kDa polypeptide of cerebellar membranes and specifically
      immunostained Purkinje cells. The delta2 antibodies recognized a 110-kDa
      polypeptide of pineal membranes and specifically immunostained huge glial-like
      cells with the occasional presence of several long, branching processes in a
      pineal cell culture. delta2 is not uniformly distributed throughout the cells and
      is relatively abundant at the periphery of the cell bodies and long processes,
      where the terminals of synaptophysin-positive processes of pinealocytes, a site
      for glutamate secretion, are frequently present. The delta2-positive cells
      constitute a very minor population among total pineal cells (approximately
      0.03%). Double immunolabeling with delta2 antibodies and antibodies against
      marker proteins for pineal interstitial cells clearly distinguishes delta2
      positive pineal cells and other known interstitial cells, including glial
      fibrillary acidic protein- or vimentin-positive glial-like cells. These results
      indicated that the delta2 glutamate receptor is expressed in a novel
      subpopulation of pineal glial-like cells in culture and suggest the presence of a
      glutamate-mediated intercellular signal transduction mechanism between
      pinealocytes and delta2-expressing cells. The pineal cells may provide a good
      experimental system for studies on the function of glutamate receptor delta2.

PMID- 10936195
TI  - Rundown of secretion after depletion of intracellular calcium stores in bovine
      adrenal chromaffin cells.
AB  - In this study, the relationship between intracellular calcium stores and
      depolarization-evoked stimulation was examined in bovine chromaffin cells, using
      changes in membrane capacitance to monitor both exocytosis and endocytosis. Cells
      were voltage-clamped using the perforated whole-cell patch configuration to
      minimize alterations in intracellular constituents. Control cells exhibited
      reproducible secretory responses each time the cell was stimulated. However, the
      same stimulation protocol elicited progressively smaller secretory responses in
      cells where their intracellular calcium store was emptied by thapsigargin.
      Transient elevation of the intracellular calcium concentration with a brief
      histamine treatment enhanced subsequent secretory responses in control but not in
      thapsigargin-treated cells. A series of depolarizations to -20 mV, which allowed
      small amounts of Ca(2+) influx but which by itself did not trigger catecholamine
      secretion, enhanced subsequent exocytosis in both control and thapsigargin
      treated cells. Caffeine-pretreated cells exhibited a rundown in the secretory
      response that was similar to that produced by thapsigargin. These results suggest
      that brief elevations of [Ca(2+)](i) could enhance subsequent secretory
      responses. In addition, the data suggest that intracellular calcium stores are
      vital for the maintenance of exocytosis during repetitive stimulation.

PMID- 10936194
TI  - Modulation of acetylcholinesterase and voltage-gated Na(+) channels in choline
      acetyltransferase- transfected neuroblastoma clones.
AB  - Neurotransmitters appear early in the developing embryo and may play a role in
      the regulation of neuronal differentiation. To study potential effects of
      acetylcholine production in neuronal differentiation, we used the FB5 subclone of
      N18TG2 murine neuroblastoma cells stably transfected with cDNA for choline
      acetyltransferase. We tested whether the forced acetylcholine production can
      modify the expression or the cellular localization of different neuronal markers.
      We studied the activity, localization, and secretion of acetylcholinesterase in
      view of its possible role in the modulation of the morphogenetic action of
      acetylcholine and of its proposed role of a regulator of neurite outgrowth. FB5
      cells are characterized by a high level of acetylcholinesterase, predominantly
      released into the culture medium. Acetylcholinesterase secretion into the medium
      was lower in choline acetyltransferase-transfected clones than in nontransfected
      and antisense-transfected controls. Moreover, sequential extraction of
      acetylcholinesterase revealed that detergent-extracted, i.e., membrane
      associated, activity was higher in the transfected clones expressing choline
      acetyltransferase activity than in both control groups. These observations
      suggest that a shift occurs in the utilization of acetylcholinesterase in choline
      acetyltransferase-transfected clones from a secretion pathway to a pathway
      leading to membrane localization. In addition, the choline acetyltransferase
      positive clones showed higher densities of voltage-gated Na(+) channels and
      enhanced high-affinity choline uptake, suggesting the accomplishment of a more
      advanced differentiated neuronal phenotype. Finally, binding experiments
      demonstrated the presence of muscarinic acetylcholine receptors in all examined
      clones. This observation is consistent with the proposed existence of an
      autocrine loop, which may be important for the enhancement in the expression of
      neurospecific traits.

PMID- 10936196
TI  - Increased exon 5 expression alters extrasynaptic NMDA receptors in cerebellar
      neurons.
AB  - We investigated the ontogenic changes in expression of alternatively spliced
      forms of NR1 protein that contain the N1 cassette (exon 5) in comparison with the
      total population of NR1 within the rat cerebellum. The N1 cassette is strongly
      developmentally regulated in the cerebellum, with >80% of total NR1 protein in
      the adult rat containing the N1 cassette. In contrast, early in development, <20%
      of NR1 protein contained this cassette. Rat cortices from the same ages did not
      show an increase in the percent of NR1 protein expressing the N1 cassette,
      indicating that the developmental changes in the cerebellum are tissue-specific.
      As the N1 cassette is known to determine NMDA receptor properties, including
      spermine sensitivity and decay kinetics of glutamate-induced currents, changes in
      the characteristics of glutamate-activated currents in granule cells from
      cerebellar slices were compared at postnatal day 7 versus 14. Glutamate responses
      exhibited fast deactivation kinetics and reduced potentiation by spermine at day
      14 while maintaining sensitivity to an NR2B-selective antagonist. These data are
      consistent with the possibility that N1 cassette expression may be a factor in
      the developmental changes in properties of extrasynaptic NMDA receptors in the
      cerebellum.

PMID- 10936197
TI  - The potent, selective mGlu2/3 receptor agonist LY379268 increases extracellular
      levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5
      hydroxyindole-3-acetic acid in the medial prefrontal cortex of the freely moving
      rat.
AB  - Previous work has shown that the potent, selective metabotropic glutamate mGlu2/3
      receptor agonist LY379268 acts like the atypical antipsychotic clozapine in
      behavioral assays. To investigate further the potential antipsychotic actions of
      this agent, we examined the effects of LY379268 using microdialysis in awake,
      freely moving rats, on extracellular levels of dopamine, 3,4
      dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole
      3-acetic acid (5-HIAA) in rat medial prefrontal cortex. Systemic LY379268
      increased extracellular levels of dopamine, DOPAC, HVA, and 5-HIAA in a dose
      dependent, somewhat delayed manner. LY379268 (3 mg/kg s.c. ) increased levels of
      dopamine, DOPAC, HVA, and 5-HIAA to 168, 170, 169, and 151% of basal,
      respectively. Clozapine (10 mg/kg) also increased dopamine, DOPAC, and HVA
      levels, with increases of 255, 262, and 173%, respectively, but was without
      effect on extracellular 5-HIAA levels by 3 mg/kg LY379268 were reversed by the
      selective mGlu2/3 receptor antagonist LY341495 (1 mg/kg). Furthermore, LY379268
      (3 mg/kg)-evoked increases in DOPAC and HVA were partially blocked and the
      increase in 5-HIAA was completely blocked by local application of 3 microM
      tetrodotoxin. Therefore, we have demonstrated that mGlu2/3 receptor agonists
      activate dopaminergic and serotonergic brain pathways previously associated with
      the action of atypical antipsychotics such as clozapine and other psychiatric
      agents.

PMID- 10936199
TI  - Mobilizing store Ca(2+) in the presence of La(3+) evokes exocytosis in bovine
      chromaffin cells.
AB  - The effect on exocytosis of La(3+), a known inhibitor of plasma membrane Ca(2+)
      ATPases and Na(+)/Ca(2+) exchangers, was studied using cultured bovine adrenal
      chromaffin cells. At high concentrations (0.3-3 mM), La(3+) substantially
      increased histamine-induced catecholamine secretion. This action was mimicked by
      other lanthanide ions (Nd(3+), Eu(3+), Gd(3+), and Tb(3+)), but not several
      divalent cations. In the presence of La(3+), the secretory response to histamine
      became independent of extracellular Ca(2+). La(3+) enhanced secretion evoked by
      other agents that mobilize intracellular Ca(2+) stores (angiotensin II,
      bradykinin, caffeine, and thapsigargin), but not that due to passive
      depolarization with 20 mM K(+). La(3+) still enhanced histamine-induced secretion
      in the presence of the nonselective inhibitors of Ca(2+)-permeant channels
      SKF96365 and Cd(2+), but the enhancement was abolished by prior depletion of
      intracellular Ca(2+) stores with thapsigargin. La(3+) inhibited (45)Ca(2+) efflux
      from preloaded chromaffin cells in the presence or absence of Na(+). It also
      enhanced and prolonged the rise in cytosolic [Ca(2+)] measured with fura-2 during
      mobilization of intracellular Ca(2+) stores with histamine in Ca(2+)-free buffer.
      The results suggest that the efficacy of intracellular Ca(2+) stores in evoking
      exocytosis is enhanced dramatically by inhibiting Ca(2+) efflux from the cell.

PMID- 10936198
TI  - Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to
      alpha7 nicotinic acetylcholine receptors.
AB  - We have recently reported evidence that a very high affinity interaction between
      the beta-amyloid peptide Abeta(1-42) and the alpha7 nicotinic acetylcholine
      receptor (alpha7nAChR) may be a precipitating event in the formation of amyloid
      plaques in Alzheimer's disease. In the present study, the kinetics for the
      binding of Abeta(1-42) to alpha7nAChR and alpha4beta2nAChR were determined using
      the subtype-selective nicotinic receptor ligands [(3)H]methyllycaconitine and
      [(3)H]cytisine. Synaptic membranes prepared from rat and guinea pig cerebral
      cortex and hippocampus were used as the source of receptors. Abeta(1-42) bound to
      the alpha7nAChR with exceptionally high affinity, as indicated by K(i) values of
      4.1 and 5.0 pM for rat and guinea pig receptors, respectively. When compared with
      the alpha7nAChR, the affinity of Abeta(1-42) for the alpha4beta2nAChR was
      approximately 5,000-fold lower, as indicated by corresponding K(i) values of 30
      and 23nM. The results of this study support the concept that an exceptionally
      high affinity interaction between Abeta(1-42) and alpha7nAChR could serve as a
      precipitating factor in the formation of amyloid plaques and thereby contribute
      to the selective degeneration of cholinergic neurons that originate in the basal
      forebrain and project to the cortex and hippocampus.

PMID- 10936200
TI  - Relative contribution of different receptor subtypes in the response of
      neuroblastoma cells to tumor necrosis factor-alpha.
AB  - The effect of tumor necrosis factor-alpha (TNF-alpha) on neuronal viability has
      been investigated in the SK-N-BE neuroblastoma cell line. These cells undergo
      differentiation upon chronic treatment with retinoic acid. Exposure of SK-N-BE
      cells to TNF-alpha produced a proliferative response in undifferentiated cells,
      whereas a reduced cell number was observed in retinoic acid (RA)-differentiated
      cultures. This biphasic response may be related to the different expression of
      TNF-alpha receptors (TNFRs); a significant increase in the density of TNFR1 was
      in fact observed following RA-induced differentiation. Under these conditions, a
      pronounced increase in the formation of ceramide-1-phosphate (which was prevented
      by the selective inhibitor of phosphatidylcholine-specific phospholipase C, D609)
      and an activation of caspase-3 upon TNF-alpha challenge were evident. Selective
      blockade of each TNFR subtype allowed a more detailed analysis of the effect
      observed. Preincubation with an anti-TNFR1 antibody prevented the cytotoxic
      effect of TNF-alpha in RA-differentiated SK-N-BE cells, whereas the anti-TNFR2
      antibody blocked the proliferative activity of the cytokine in undifferentiated
      cultures.

PMID- 10936201
TI  - Coupling of canine serotonin 5-HT(1B) and 5-HT(1D) receptor subtypes to the
      formation of inositol phosphates by dual interactions with endogenous G(i/o) and
      recombinant G(alpha15) proteins.
AB  - Molecular cloning and expression of canine (ca) serotonin 5-HT(1B) and ca 5
      HT(1D) receptor subtypes showed that besides the lower binding affinity of
      ketanserin for the ca 5-HT(1D) receptor, the ligand binding profiles were similar
      to their human homologues. Site-directed mutagenesis studies suggest that a
      Gln(189) residue in the second extracellular loop of the ca 5-HT(1D) receptor may
      partially account for the lower binding affinity of ketanserin. The coupling of
      ca 5-HT(1B) and ca 5-HT(1D) receptor subtypes to the phospholipase C pathway was
      analyzed by measuring stimulation of inositol phosphate formation in COS-7 cells.
      Zolmitriptan potently stimulated (EC(50) = 4.9 nM) the inositol phosphate
      formation at ca 5-HT(1D) receptors in a fully pertussis toxin (PTX)-dependent
      manner, whereas only a weak PTX-resistant inositol phosphate response (26-29% at
      10 microM zolmitriptan) could be detected for the ca 5-HT(1B) receptor at a
      similar expression level. In contrast, both ca 5-HT(1B) and ca 5-HT(1D) receptor
      subtypes yielded a similar maximal magnitude of inositol phosphate formation (300
      340% at 10 microM zolmitriptan) upon co-expression with a mouse (m) G(alpha15)
      protein. PTX treatment and co-expression with a beta-adrenergic receptor kinase C
      terminal polypeptide partially (20-46%) abolished the m G(alpha15) protein
      dependent ca 5-HT(1B) and ca 5-HT(1D) receptor-mediated stimulation of inositol
      phosphate formation. This study suggests both 5-HT receptor subtypes can activate
      betagamma subunits of endogenous G(i/o) proteins besides their coupling to
      recombinant m G(alpha15) protein.

PMID- 10936202
TI  - Coupling efficacy and selectivity of the human mu-opioid receptor expressed as
      receptor-Galpha fusion proteins in Escherichia coli.
AB  - Two constructs encoding the human micro-opioid receptor (hMOR) fused at its C
      terminus to either one of two Galpha subunits, Galpha(o1) (hMOR-Galpha(o1)) and
      Galpha(i2) (hMOR-Galpha(i2)), were expressed in Escherichia coli at levels
      suitable for pharmacological studies (0.4-0.5 pmol/mg). Receptors fused to
      Galpha(o1) or to Galpha(i2) maintained high-affinity binding of the antagonist
      diprenorphine. Affinities of the micro-selective agonists morphine, [D-Ala(2),N
      Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), and endomorphins as well as their
      potencies and intrinsic activities in stimulating guanosine 5'-O-(3
      [(35)S]thiotriphosphate) ([(35)S]GTPgammaS) binding were assessed in the presence
      of added purified Gbetagamma subunits. Both fusion proteins displayed high
      affinity agonist binding and agonist-stimulated [(35)S]GTPgammaS binding. In the
      presence of Gbetagamma dimers, the affinities of DAMGO and endomorphin-1 and -2
      were higher at hMOR-Galpha(i2) than at hMOR-Galpha(o1), whereas morphine
      displayed similar affinities at the two chimeras. Potencies of the four agonists
      in stimulating [(35)S]GTPgammaS binding at hMOR-Galpha(o1) were similar, whereas
      at hMOR-Galpha(i2), endomorphin-1 and morphine were more potent than DAMGO and
      endomorphin-2. The intrinsic activities of the four agonists at the two fusion
      constructs were similar. The results confirm hMOR coupling to Galpha(o1) and
      Galpha(i2) and support the hypothesis of the existence of multiple receptor
      conformational states, depending on the nature of the G protein to which it is
      coupled.

PMID- 10936203
TI  - MPTP activates c-Jun NH(2)-terminal kinase (JNK) and its upstream regulatory
      kinase MKK4 in nigrostriatal neurons in vivo.
AB  - The neuropathology of Parkinson's disease is reflected in experimental animals
      treated with the selective nigrostriatal dopaminergic neurotoxin MPTP. Neurons
      exposed to MPTP (MPP(+)) express morphological features of apoptosis, although
      the intracellular pathways that produce this morphology have not been
      established. The c-Jun NH(2)-terminal kinase (JNK) signaling cascade has been
      implicated as a mediator of MPTP-induced apoptotic neuronal death based on the
      ability of CEP-1347/KT-7515, an inhibitor of JNK activation, to attenuate MPTP
      induced nigrostriatal dopaminergic degeneration. In these studies, MPTP-mediated
      activation of the JNK signaling pathway was assessed in the nigrostriatal system
      of MPTP-treated mice. MPTP elevated levels of phosphorylated JNK and JNK kinase
      (MKK4; also known as SEK1 or JNKK), by 2.5- and fivefold, respectively. Peak
      elevations occurred soon after administration of MPTP and coincided with peak CNS
      levels of MPP(+). Increased MKK4 phosphorylation, but not JNK phosphorylation,
      was found in the striatum, suggesting that activation of MKK4 occurs in injured
      dopaminergic terminals. Both JNK and MKK4 phosphorylations were attenuated by
      pretreatment with l-deprenyl, indicating that these phosphorylation events were
      mediated by MPP(+). Moreover, CEP-1347/KT-7515 inhibited MPTP-mediated MKK4 and
      JNK signaling at a dose that attenuates MPTP-induced dopaminergic loss. These
      data implicate this signaling pathway in MPTP-mediated nigrostriatal dopaminergic
      death and suggest that it may be activated in the degenerative process in
      Parkinson's disease.

PMID- 10936204
TI  - Pilocarpine-induced status epilepticus causes N-methyl-D-aspartate receptor
      dependent inhibition of microsomal Mg(2+)/Ca(2+) ATPase-mediated Ca(2+) uptake.
AB  - Status epilepticus is associated with sustained and elevated levels of cytosolic
      Ca(2+). To elucidate the mechanisms associated with changes of cytosolic Ca(2+)
      after status epilepticus, this study was initiated to evaluate the effect of
      pilocarpine-induced status epilepticus on Mg(2+)/Ca(2+) ATPase-mediated Ca(2+)
      uptake in microsomes isolated from rat cortex, because the Ca(2+) uptake
      mechanism plays a major role in regulating intracellular Ca(2+) levels. The data
      demonstrated that the initial rate and overall Ca(2+) uptake in microsomes from
      pilocarpine treated animals were significantly inhibited compared with those in
      microsomes from saline-treated control animals. It was also shown that the
      inhibition of Ca(2+) uptake caused by status epilepticus was not an artifact of
      increased Ca(2+) release from microsomes, selective isolation of damaged
      microsomes from the homogenate, or decreased Mg(2+)/Ca(2+) ATPase protein in the
      microsomes. Pretreatment with the NMDA antagonist dizocilpine maleate blocked
      status epilepticus-induced inhibition of the initial rate and overall Ca(2+)
      uptake. The data suggest that inhibition of microsomal Mg(2+)/Ca(2+) ATPase
      Ca(2+) uptake is involved in NMDA-dependent deregulation of cytosolic Ca(2+)
      homeostasis associated with status epilepticus.

PMID- 10936205
TI  - Characterization of copper interactions with alzheimer amyloid beta peptides:
      identification of an attomolar-affinity copper binding site on amyloid beta1-42.
AB  - Cu and Zn have been shown to accumulate in the brains of Alzheimer's disease
      patients. We have previously reported that Cu(2+) and Zn(2+) bind amyloid beta
      (Abeta), explaining their enrichment in plaque pathology. Here we detail the
      stoichiometries and binding affinities of multiple cooperative Cu(2+)-binding
      sites on synthetic Abeta1-40 and Abeta1-42. We have developed a ligand
      displacement technique (competitive metal capture analysis) that uses metal
      chelator complexes to evaluate metal ion binding to Abeta, a notoriously self
      aggregating peptide. This analysis indicated that there is a very-high-affinity
      Cu(2+)-binding site on Abeta1-42 (log K(app) = 17.2) that mediates peptide
      precipitation and that the tendency of this peptide to self-aggregate in aqueous
      solutions is due to the presence of trace Cu(2+) contamination (customarily
      approximately 0.1 microM). In contrast, Abeta1-40 has much lower affinity for
      Cu(2+) at this site (estimated log K(app) = 10.3), explaining why this peptide is
      less self-aggregating. The greater Cu(2+)-binding affinity of Abeta1-42 compared
      with Abeta1-40 is associated with significantly diminished negative
      cooperativity. The role of trace metal contamination in inducing Abeta
      precipitation was confirmed by the demonstration that Abeta peptide (10 microM)
      remained soluble for 5 days only in the presence of high-affinity Cu(2+)
      selective chelators.

PMID- 10936206
TI  - In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of
      tau induced by 4-hydroxy-2-nonenal modification.
AB  - In this study, we compared the neuronal induction of the antioxidant heme
      oxygenase-1 (HO-1) in Alzheimer's disease with abnormalities in tau marked by
      antibodies recognizing either phosphorylation (AT8) or conformational change
      (Alz50). The epitope recognized by Alz50 shows a complete overlap with HO-1
      containing neurons, but AT8 recognized these neurons as well as neurons not
      displaying HO-1. These findings suggest that tau phosphorylation precedes the HO
      1 response and that HO-1 is coincident with the Alz50 epitope. This led us to
      consider whether oxidative damage plays a role in forming the Alz50 epitope. We
      found that 4-hydroxy-2-nonenal (HNE), a highly reactive product of lipid
      peroxidation, reacts with normal tau and induces the Alz50 epitope in tau. It is
      important that the ability of HNE to create the Alz50 epitope not only is
      dependent on lysine residues of tau but also requires tau phosphorylation because
      neither methylated, recombinant, nor dephosphorylated tau reacts with HNE to
      create the Alz50 epitope. Supporting the in vivo relevance of this observation,
      endogenous paired helical filament-tau isolated from subjects with Alzheimer's
      disease was immunoreactive with an antibody to a stable HNE-lysine adduct, as
      were all vulnerable neurons in subjects with Alzheimer's disease but not in
      control individuals. Together, these findings support the involvement of
      oxidative damage early in neurofibrillary tangle formation in Alzheimer's disease
      and also suggest that HNE modification contributes to the generation of the tau
      conformation defining the Alz50 epitope. These findings provide evidence that an
      interplay between phosphorylation of tau and neuronal oxidative stress-induced
      pathology is important in the formation of neurofibrillary tangles.

PMID- 10936207
TI  - Diazepam promotes ATP recovery and prevents cytochrome c release in hippocampal
      slices after in vitro ischemia.
AB  - Benzodiazepines protect hippocampal neurons when administered within the first
      few hours after transient cerebral ischemia. Here, we examined the ability of
      diazepam to prevent early signals of cell injury (before cell death) after in
      vitro ischemia. Ischemia in vitro or in vivo causes a rapid depletion of ATP and
      the generation of cell death signals, such as the release of cytochrome c from
      mitochondria. Hippocampal slices from adult rats were subjected to 7 min of
      oxygen-glucose deprivation (OGD) and assessed histologically 3 h after
      reoxygenation. At this time, area CA1 neurons appeared viable, although slight
      abnormalities in structure were evident. Immediately following OGD, ATP levels in
      hippocampus were decreased by 70%, and they recovered partially over the next 3 h
      of reoxygenation. When diazepam was included in the reoxygenation buffer, ATP
      levels recovered completely by 3 h after OGD. The effects of diazepam were
      blocked by picrotoxin, indicating that the protection was mediated by an influx
      of Cl(-) through the GABA(A) receptor. It is interesting that the benzodiazepine
      antagonist flumazenil did not prevent the action of diazepam, as has been shown
      in other studies using the hippocampus. Two hours after OGD, the partial recovery
      of ATP levels occurred simultaneously with an increase of cytochrome c
      (approximately 400%) in the cytosol. When diazepam was included in the
      reoxygenation buffer, it completely prevented the increase in cytosolic
      cytochrome c. Thus, complete recovery of ATP and prevention of cytochrome c
      release from mitochondria can be achieved when diazepam is given after the loss
      of ATP induced by OGD.

PMID- 10936208
TI  - Regional and developmental expression of the Npc1 mRNA in the mouse brain.
AB  - Niemann-Pick type C (NP-C) disease is a fatal, autosomal recessive disorder of
      cholesterol metabolism that results in progressive central nervous system
      deterioration and premature death. Recently, a gene mutated in NP-C disease
      (NPC1) was identified in both human patients and in the npc(nih) mouse model.
      Although the function of the NPC1 gene is at present unknown, determining the
      pattern of its expression in the brain may facilitate identification of the
      mechanisms underlying the neuropathology of this disease and in identifying
      relevant targets for any potential therapeutic intervention. We have used in situ
      hybridization techniques to characterize the pattern of Npc1 mRNA expression in
      both the wild-type and the npc(nih) mutant mouse brain. In adult animals of both
      genotypes, the Npc1 mRNA was detected in the majority of neurons in nearly all
      regions, but at significantly higher levels in the cerebellum and in specific
      pontine nuclei. Analysis of Npc1 mRNA levels during development in the wild-type
      mouse indicated that this transcript was expressed in neurons as early as
      embryonic day 15 and that a significant region-specific pattern of expression was
      established by postnatal day 7. Our data suggest that whereas the NPC1 gene is
      widely expressed in neurons of the brain, the higher levels of expression in the
      cerebellum and pontine structures established by early postnatal ages may make
      these regions more susceptible to neuronal dysfunction in NP-C disease.

PMID- 10936209
TI  - Prevention of beta-amyloid neurotoxicity by blockade of the ubiquitin-proteasome
      proteolytic pathway.
AB  - In many neurodegenerative disorders, such as Alzheimer's disease, inclusions
      containing ubiquitinated proteins have been found in the brain, suggesting a
      pathophysiological role for ubiquitin-mediated proteasomal degradation of
      neuronal proteins. Here we show for the first time that the beta-amyloid fragment
      1-40, which in micromolar levels causes the death of cortical neurons, also
      induces the ubiquitination of several neuronal proteins. Prevention of
      ubiquitination and inhibition of proteasome activity block the neurotoxic effect
      of beta-amyloid. These data suggest that beta-amyloid neurotoxicity may cause
      toxicity through the activation of protein degradation via the ubiquitin
      proteasome pathway. These findings suggest possible new pharmacological targets
      for the prophylaxis and/or treatment of Alzheimer's disease and possibly for
      other related neurodegenerative disorders.

PMID- 10936210
TI  - Temporal profile and cell subtype distribution of activated caspase-3 following
      experimental traumatic brain injury.
AB  - This study investigated the temporal expression and cell subtype distribution of
      activated caspase-3 following cortical impact-induced traumatic brain injury in
      rats. The animals were killed and examined for protein expression of the
      proteolytically active subunit of caspase-3, p18, at intervals from 6 h to 14
      days after injury. In addition, we also investigated the effect of caspase-3
      activation on proteolysis of the cytoskeletal protein alpha-spectrin. Increased
      protein levels of p18 and the caspase-3-specific 120-kDa breakdown product to
      alpha-spectrin were seen in the cortex ipsilateral to the injury site from 6 to
      72 h after the trauma. Immunohistological examinations revealed increased
      expression of p18 in neurons, astrocytes, and oligodendrocytes from 6 to 72 h
      following impact injury. In contrast, no evidence of caspase-3 activation was
      seen in microglia at all time points investigated. Quantitative analysis of
      caspase-3-positive cells revealed that the number of caspase-3-positive neurons
      exceeded the number of caspase-3-positive glia cells from 6 to 72 h after injury.
      Moreover, concurrent assessment of nuclear histopathology using hematoxylin
      identified p18-immunopositive cells exhibiting apoptotic-like morphological
      profiles in the cortex ipsilateral to the injury site. In contrast, no evidence
      of increased p18 expression or alpha-spectrin proteolysis was seen in the
      ipsilateral hippocampus, contralateral cortex, or hippocampus up to 14 days after
      the impact. Our results are the first to demonstrate the concurrent expression of
      activated caspase-3 in different CNS cells after traumatic brain injury in the
      rat. Our findings also suggest a contributory role of activated caspase-3 in
      neuronal and glial apoptotic degeneration after experimental TBI in vivo.

PMID- 10936211
TI  - Identification of an amino acid sequence motif in the cytoplasmic domain of the
      NCAM-140 kDa isoform essential for its neuritogenic activity.
AB  - The functions of the extracellular domains of neural cell adhesion molecule
      (NCAM) have been studied extensively, whereas the roles of the cytoplasmic
      domains of the transmembrane forms of NCAM are less elucidated. We investigated
      the importance of the cytoplasmic domain of the 140-kDa NCAM isoform (cytNCAM
      140) and of the 180-kDa NCAM isoform (cytNCAM-180) in NCAM-induced neurite
      extension by estimating NCAM-dependent neurite outgrowth from PC12-E2 cells grown
      in coculture with NCAM-negative or NCAM-positive fibroblasts. PC12-E2 cells were
      transiently transfected with expression plasmids encoding cytNCAM-140, cytNCAM
      180, the constitutively active form of the mitogen-activated protein (MAP)
      kinase/extracellular signal-regulated kinase kinase (MEK2), and the enhanced
      variant of the green fluorescent protein (EGFP). EGFP expression was used for
      identification of transfected cells. We found that expression of cytNCAM-180 had
      no effect on NCAM-stimulated neuritogenesis, whereas expression of cytNCAM-140
      strongly inhibited this process. However, if MEK2 was expressed concomitantly
      with cytNCAM-140, neurite outgrowth was rescued, indicating that cytNCAM-140 is
      involved in signaling via the Ras-MAP kinase pathway. PC12-E2 cells were
      subsequently transiently transfected with constructs encoding a series of
      fragments of cytNCAM-140 and various full-length cytNCAM-140 mutants, and the
      residues Thr-Glu-Val-Lys-Thr (839-843) were identified as essential in NCAM
      stimulated neuritogenesis. The combined substitution of Glu(840) and Lys(842)
      with Ala abrogated the effect of the construct, assigning a critical role to
      these two residues.

PMID- 10936212
TI  - Site-directed mutations in the third intracellular loop of the serotonin 5-HT(1A)
      receptor alter G protein coupling from G(i) to G(s) in a ligand-dependent manner.
AB  - The effect of mutations (V344E and T343A/V344E) in the third intracellular loop
      of the serotonin 5-HT(1A) receptor expressed transiently in human embryonic
      kidney 293 cells have been examined in terms of receptor/G protein interaction
      and signaling. Serotonin, (R)-8-hydroxy-2-dipropylaminotetralin [(R)-8-OH-DPAT],
      and buspirone inhibited cyclic AMP production in cells expressing native and
      mutant 5-HT(1A) receptors. Serotonin, however, produced inverse bell-shaped
      cyclic AMP concentration-response curves at native and mutant 5-HT(1A) receptors,
      indicating coupling not only to G(i)/G(o), but also to G(s). (R)-8-OH-DPAT,
      however, induced stimulation of cyclic AMP production only after inactivation of
      G(i)/G(o) proteins by pertussis toxin and only at the mutant receptors. The
      partial agonist buspirone was unable to induce coupling to G(s) at any of the
      receptors, even after pertussis toxin treatment. The basal activities of native
      and mutant 5-HT(1A) receptors in suppressing cyclic AMP levels were not found to
      be significantly different. The receptor binding characteristics of the native
      and mutant receptors were investigated using the novel 5-HT(1A) receptor
      antagonist [(3)H]NAD-299. For other receptors, analogous mutations have produced
      constitutive activation. This does not occur for the 5-HT(1A) receptor, and for
      this receptor the mutations seem to alter receptor/G protein coupling, allowing
      ligand-dependent coupling of receptor to G(s) in addition to G(i)/G(o) proteins.

PMID- 10936213
TI  - Insect nicotinic acetylcholine receptor: conserved neonicotinoid specificity of
      [(3)H]imidacloprid binding site.
AB  - The insect nicotinic acetylcholine receptor (nAChR) is a major target for
      insecticide action. The rapidly expanding use of neonicotinoid insecticides of
      varied structures makes it increasingly important to define similarities and
      differences in their action, particularly for the first-generation
      chloropyridinyl compounds versus the second-generation chlorothiazolyl
      derivatives. We have shown with Musca domestica that a convenient and relevant
      determination of the neonicotinoid insecticide target is a binding site assay
      with [(3)H]imidacloprid ([(3)H]IMI). This study uses membranes from the aphids
      MYZUS: persicae and Aphis craccivora and from heads of the flies Drosophila
      melanogaster and Musca domestica to characterize the [(3)H]IMI binding sites
      relative to their number and possible species variation in structure-activity
      relationships. With emphasis on commercial neonicotinoids, six potent
      chloropyridinyl compounds are compared with the corresponding six chlorothiazolyl
      analogues (syntheses are given for chemicals prepared differently than previously
      described). The preference for chloropyridinyl versus chlorothiazolyl is not
      dependent on the insect species examined but instead on other structural features
      of the molecule. The chlorothiazolyl substituent generally confers higher potency
      in the clothianidin and desmethylthiamethoxam series and the chloropyridinyl
      moiety in the imidacloprid, thiacloprid, acetamiprid, and nitenpyram series. Two
      chlorothiazolyl compounds compete directly with the chloropyridinyl [(3)H]IMI for
      the same binding sites in Myzus and Drosophila membranes. This study shows
      conserved neonicotinoid specificity of the [(3)H]IMI binding site in each of the
      four insect species examined.

PMID- 10936214
TI  - Phe(208) and Ile(199) in human monoamine oxidase A and B do not determine
      substrate and inhibitor specificities as in rat.
AB  - It has been reported previously that reciprocally switching Phe(208) and Ile(199)
      in rat monoamine oxidase (MAO) A and B, respectively, was sufficient to switch
      their substrate and inhibitor preferences. In this study, the same mutants were
      made in the human forms of MAO. When compared with MAO A, MAO A-F208I showed a
      sixfold decrease in the specificity constant k(cat)/K(m) for both the MAO A- and
      the MAO B-preferring substrates 5-hydroxytryptamine and beta-phenylethylamine,
      respectively. The reciprocal point mutant MAO B-I199F had no effect on substrate
      affinity. To investigate if the region neighboring these two residues is
      responsible for conferring preferences, we have also made chimeric constructs by
      reciprocally switching the corresponding amino acid segments 159-214 in MAO A and
      150-205 in MAO B. Chimerics MAO AB(159-214)A and MAO BA(150-205)B had small
      changes in K(m) and IC(50) values when compared with MAO A and B, respectively,
      but did not exhibit a preference switch. The results suggest that Phe(208) in MAO
      A and amino acid segments 159-214 and 150-205 in MAO A and B, respectively,
      influence the enzyme active site. However, substrate and inhibitor preferences of
      human MAO A and B are not determined by the respective residues Phe(108) and
      Ile(199) as in rat MAO nor by their neighboring regions.

PMID- 10936215
TI  - Complementation of physiological and behavioral defects by a slowpoke Ca(2+) 
      activated K(+) channel transgene.
AB  - The Drosophila slowpoke gene encodes a large conductance calcium-activated
      potassium channel used in neurons, muscle, and some epithelial cells. Tissue
      specific transcriptional promoters and alternative mRNA splicing generate a large
      array of transcripts. These distinct transcripts are thought to tailor the
      properties of the channel to the requirements of the cell. Presumably, a single
      splice variant cannot satisfy the specific needs of all cell types. To test this,
      we examined whether a single slowpoke splice variant was capable of complementing
      all slowpoke behavioral phenotypes. Null mutations in slowpoke cause animals to
      be semiflightless and to manifest an inducible "sticky-feet" phenotype. The well
      characterized slowpoke transcriptional control region was used to direct the
      expression of a single slowpoke splice variant (cDNA H13) in transgenic flies.
      The endogenous gene in these flies had been inactivated by the slo(4) mutation.
      Action-potential recordings and voltage-clamp recordings demonstrated the
      production of functional channels from the transgene. The transgene completely
      complemented the flight defect, but not the sticky-feet phenotype. We conclude
      that distinct slowpoke channel isoforms, produced by alternative splicing, are
      not interchangeable and are required for proper function of different cell types.

PMID- 10936217
TI  - Tau promoter activity in neuronally differentiated P19 cells.
AB  - Tau proteins are encoded by a single gene which is regulated by a unique
      promoter. The proximal 196 base pairs of the tau 5' flanking region confers tau
      protein with neuronal specific expression and nerve growth factor inducibility.
      We tested tau promoter activity in neuronally differentiated embryonal carcinoma
      cells, the P19 mouse blastoderm cell line. In these experiments, we examined the
      temporal expression pattern of the tau promoter and compared it to other viral
      and cellular promoters. Tau promoter activity increases significantly with
      differentiation, specifically during neurite initiation. In addition, tau
      promoter activity in neuronally differentiated P19 cells was significantly
      greater than all five of the other neuronal or non neuronal promoters tested. All
      other promoters displayed low levels of promoter activity throughout retinoic
      acid induced neuronal differentiation of P19 cells. Taken together, our results
      suggest that the tau promoter is a good choice for ectopic expression of
      exogenous genes in P19 cells, which serves as a differentiating neuronal model
      system.

PMID- 10936216
TI  - Abundant tissue butyrylcholinesterase and its possible function in the
      acetylcholinesterase knockout mouse.
AB  - We have described recently an acetylcholinesterase (AChE) knockout mouse. While
      comparing the tissue distribution of AChE and butyrylcholinesterase (BChE), we
      found that extraction buffers containing Triton X-100 strongly inhibited mouse
      BChE activity. In contrast, buffers with Tween 20 caused no inhibition of BChE.
      Conventional techniques grossly underestimated BChE activity by up to 15-fold. In
      Tween 20 buffer, the intestine, serum, lung, liver, and heart had higher BChE
      than AChE activity. Only brain had higher AChE than BChE activity in AChE +/+
      mice. These findings contradict the dogma, based mainly on observations in Triton
      X-100 extracts, that BChE is a minor cholinesterase in animal tissues. AChE +/-
      mice had 50% of normal AChE activity and AChE -/- mice had none, but all mice had
      similar levels of BChE activity. BChE was inhibited by Triton X-100 in all
      species tested, except rat and chicken. Inhibition was reversible and competitive
      with substrate binding. The active site of rat BChE was unique, having an
      arginine in place of leucine at position 286 (human BChE numbering) in the acyl
      binding pocket of the active site, thus explaining the lack of inhibition of rat
      BChE by Triton X-100. The generally high levels of BChE activity in tissues,
      including the motor endplate, and the observation that mice live without AChE,
      suggest that BChE has an essential function in nullizygous mice and probably in
      wild-type mice as well.

PMID- 10936218
TI  - The influence of lorazepam on somatosensory-evoked fast frequency (600 Hz)
      activity in MEG.
AB  - The generators of high frequency bursts (600-Hz activity) detected at the
      parietal scalp over the primary somatosensory cortex after electrical stimulation
      of peripheral nerves are not yet known. We investigated the influence of
      benzodiazepine on the somatosensory-evoked 600-Hz activity by means of
      neuromagnetic measurements and source analysis. After oral administration of
      lorazepam, the latency of the 600-Hz burst activity was increased; specifically
      later peaks were delayed more than earlier peaks. In contrast, the latency of the
      concurrent primary cortical low frequency response (N20m) was not significantly
      changed. The source strengths of both N20m and 600-Hz bursts were significantly
      increased. Our results provide evidence for two components of the 600-Hz activity
      with a different generator structure.

PMID- 10936219
TI  - Phenidone prevents kainate-induced neurotoxicity via antioxidant mechanisms.
AB  - Acculmulating evidence indicates that a marked generation of oxygen free radicals
      derived from the metabolism of arachidonic acid causes neurodegeneration.
      Recently, we have demonstrated that the novel antioxidant actions mediated by
      phenidone, a dual inhibitor of cyclooxygenase/lipoxygenase pathways, may play a
      crucial role in preventing neuroexcitotoxicity in vitro [Neurosci. Lett. 272
      (1999) 91], and that phenidone significantly attenuates kainic acid (KA)-induced
      seizures via inhibiting the synthesis of Fos-related antigen protein [Brain Res.
      782 (1998) 337]. In order to extend our understanding of the pharmacological
      intervention of phenidone, we evaluated the antioxidant activity of this compound
      in vivo in the present study. In order to better understand the significance of a
      blockade of both the cyclooxygenase and lipoxygenase pathways, we studied the
      effects of aspirin (ASP; a non-selective inhibitor of cyclooxygenase), NS-398 (a
      selective inhibitor of cyclooxygenase-2), esculetin (an inhibitor of
      lipoxygenase) and phenidone on lipid peroxidation, protein oxidation, and
      glutathione (GSH) status in the rat hippocampus after KA administration. ASP (7.5
      or 15 mg/kg), NS-398 (10 or 20 mg/kg), esculetin (5 or 10 mg/kg) or phenidone
      (25, 50 or 100 mg/kg) was administered orally five times every 12 h before the
      injection of KA (10 mg/kg, i.p.). The KA-induced toxic behavioral signs,
      oxidative stress (lipid peroxidation and protein oxidation), impairment of GSH
      status, and the loss of hippocampal neurons were dose-dependently attenuated by
      the phenidone, NS-398+esculetin, and ASP+esculetin. However, ASP, NS-398 and
      esculetin alone failed to protect against the neurotoxicities induced by KA.
      Therefore, the results suggest that protection by blockade of both cyclooxygenase
      and lipoxygenase pathways against KA-induced neuroexcitotoxicity is via
      antioxidant actions. However, a novel anticonvulsant/neuroprotective effect
      mediated by phenidone remains to be further characterized.

PMID- 10936220
TI  - Sex hormone binding globulin stimulates female sexual receptivity.
AB  - Sex hormone binding globulin (SHBG) is found in the brain and acts directly on
      plasma membrane-associated receptors in the prostate gland. Infusing SHBG into
      the medial preoptic area or medial basal hypothalamus of female rats increases
      their female sexual receptivity. SHBG, SHBG plus estradiol (SHBG-E), and SHBG-E
      plus oxytocin all significantly increased female sexual receptivity over vehicle
      or estradiol plus oxytocin infused controls, as measured by lordosis quotients
      and receptivity scores, at 40, and 90 min after their infusions into the medial
      preoptic area. When infused into the medial basal hypothalamus, SHBG-E plus
      oxytocin resulted in significantly increased sexual receptivity 20 and 40 min
      after infusion when compared to its estradiol plus oxytocin control group. SHBG
      produced in the brain may be released endogenously to have immediate effects on
      reproductive physiology and behavior.

PMID- 10936221
TI  - Intracerebroventricular injection of murine leptin enhances the postprandial
      metabolic rate in the rat.
AB  - Energy balance is achieved by means of a concomitant control of both food intake
      and energy expenditure. Leptin, synthesized in the adipose tissue, acts on brain
      structures and lowers body weight by inhibiting food intake and in parallel by
      enhancing energy expenditure i.e. metabolism or one of its components. Recording
      distinctly these components allowed us to assess the effect of an acute
      intracerebroventricular injection of leptin on both feeding pattern and
      background metabolism (i.e. energy expenditure free from the part of locomotor
      activity), respiratory quotient, feeding-related metabolism and locomotor
      activity-related metabolism. Leptin injection to Sprague-Dawley male rats induced
      an inhibition of feeding that began 90 min after the treatment and lasted 1 h
      before to return to the control feeding pattern level. Considering this late
      behavioral effect, it appeared that leptin may act during the postprandial period
      so that we recorded the different metabolic parameters following a 3 g calibrated
      meal itself preceded by leptin vs. artificial cerebrospinal fluid injection.
      Postprandial respiratory quotient was rapidly lowered in leptin-treated animals
      and subsequent background metabolism increased for 6 h. Thus it appeared that
      leptin increased the duration of the postprandial metabolic rate via the
      recruitment of endogenous fat stores. Enhancement in the thermic effect of food
      may be the reason for feeding behavior inhibition to be delayed.

PMID- 10936222
TI  - Ectopic neural activity from myelinated afferent fibres in the lingual nerve of
      the ferret following three types of injury.
AB  - Sensory disturbances following nerve injury may result from abnormal neural
      activity initiated at the injury site. We have studied the activity generated in
      the lingual nerve after three types of injury which may have variable potentials
      for the initiation of sensory disturbances. We have also compared the results
      with those found after damage to the inferior alveolar nerve, another branch of
      the trigeminal nerve, to determine whether differences in nerve fibre type or
      location affect the level of abnormal activity. In anaesthetised adult male
      ferrets the left lingual nerve was either ligated and cut distally, chronically
      constricted, or sectioned and allowed to regenerate. Following recovery periods
      of 3 days-6 months, single unit electrophysiological recordings were made from
      central to the injury site. After all three types of injury, some of the damaged
      axons at the injury site developed spontaneous activity (up to 36% of units) and
      mechanical sensitivity (up to 35% of units). There were significantly fewer
      spontaneously active units after ligation than after the other two types of
      injury but the level of mechanical sensitivity was not significantly different
      between the three types of injury. There was a significant increase in the
      spontaneous activity between 3 weeks and later recovery periods following both
      ligation and section injuries, and this late increase was not seen in our
      previous studies on the inferior alveolar nerve. Differences in the time-course
      of ectopic activity in adjacent branches of the trigeminal nerve suggest that the
      fibre types or anatomical relationships affect the outcome of injury.

PMID- 10936223
TI  - Trigemino-autonomic connections in the muskrat: the neural substrate for the
      diving response.
AB  - Stimulation of the anterior ethmoidal nerve of the muskrat produces a
      cardiorespiratory depression similar to the diving response. This includes an
      apnea, a parasympathetic bradycardia, and a selective increase in sympathetic
      vascular tone. However, the brainstem circuitry that links the afferent stimulus
      to the efferent autonomic responses is unknown. We used the anterograde
      transneuronal transport of the herpes simplex virus (HSV-1), strain 129, after
      its injection into the anterior ethmoidal nerve to determine the primary,
      secondary, and tertiary brainstem relays responsible for this cardiorespiratory
      response. In an effort to check the validity of this relatively untested tracer,
      we also injected the medullary dorsal horn with biotinylated dextran amine to
      determine the secondary trigemino-autonomic projections. Approximately 1 microl
      (6x10(6) PFU) of the HSV-1 virus was injected directly into the anterior
      ethmoidal nerve of muskrats. After 2-6 days, their trigeminal ganglions, spinal
      cords and brainstems were cut and immunohistologically processed for HSV-1.
      Initially (2 days), HSV-1 was observed only in the trigeminal ganglion. After
      approximately 3 days, HSV-1 was observed first in many brainstem areas optimally
      labeled between 4 and 4.5 days. In these cases, the ventrolateral superficial
      medullary dorsal horn, the ventral paratrigeminal nucleus and the interface
      between the interpolar and caudal subnuclei were labeled ipsilaterally. The
      nucleus tractus solitarius (NTS), especially its ventrolateral, dorsolateral, and
      commissural subnuclei were labeled as well as the caudal, intermediate and
      rostral ventrolateral medulla. Within the pons, the superior salivatory nucleus,
      the A5 area, the ventrolateral part of the parabrachial nucleus and the Kolliker
      Fuse nucleus were labeled. Only after a survival of 4 days or more, the locus
      coeruleus, the nucleus raphe magnus, the nucleus paragigantocellularis, pars
      alpha, and the pontine raphe nucleus were labeled. Injections of biotinylated
      dextran amine were made into the medullary dorsal horn (MDH) in a location
      similar to that labeled after the viral injections. Fine fibers and terminals
      were labeled in the same brainstem areas labeled after injections of HSV-1 into
      the anterior ethmoidal nerve. This study outlines the potential brainstem circuit
      for the diving response, the most powerful autonomic reflex known. It also
      confirms the efficacy for using HSV-1, strain 129, as an anterograde
      transneuronal transport method.

PMID- 10936224
TI  - Anterograde tracing of retinal afferents to the tree shrew hypothalamus and
      raphe.
AB  - The anterograde neuronal transport of Cholera toxin B subunit (CTB) was used in
      this study to label the termination of retinal afferents in the hypothalamus of
      the tree shrew Tupaia belangeri. Upon pressure-injection of the substance into
      the vitreous body of one eye, a major projection of the retinohypothalamic tract
      (RHT) was found to the hypothalamic suprachiasmatic nuclei (SCN). Although the
      innervation pattern was bilateral, the ipsilateral SCN received a somewhat
      stronger projection. Labeling was also found in the supraoptic nucleus and its
      perinuclear zone, respectively, mainly ipsilaterally as well as in the bilateral
      para- and periventricular hypothalamic regions without lateral predominance. In
      the raphe region, scattered fibers and terminals were seen in the dorsal and
      median raphe nuclei. CTB-immunoreactive structures were observed neither in the
      locus ceruleus nor in vagal nuclei. Our results, partly in contradiction to
      earlier studies using different tracing techniques in another tree shrew species
      (Tupaia glis), reveal that hypothalamic nuclei, in particular the SCN, are
      contacted by retino-afferent fibers which are thought to mediate the effects of
      light to the endogenous 'clock' and to parts of the neuroendocrine system.

PMID- 10936225
TI  - Neuroprotective activity of tiagabine in a focal embolic model of cerebral
      ischemia.
AB  - Gamma aminobutyric acid (GABA) agonists have been shown to have neuroprotective
      effects when used after focal or global cerebral ischemia. In this study, we
      evaluated the neuroprotective effects of a GABA re-uptake inhibitory agent,
      tiagabine, on focal ischemic brain injury in an embolic model in rats. Tiagabine,
      injected at 1 h after embolization, significantly reduced brain infarction
      volume, measured with 2,3,5-triphenyltetrazolium chloride (TTC) histological
      assay. There were varying degrees of neuroprotective effect exhibited in the
      other experimental groups however this did not reach significance. These results
      suggest that tiagabine is neuroprotective when administrated at an early period
      after the ischemic brain injury.

PMID- 10936226
TI  - Antinociceptive effects of morphine injected into the nucleus parafascicularis
      thalami of the rat.
AB  - The antinociceptive action of morphine microinjected into the nucleus
      parafascicularis thalami (nPf) on pain behaviors organized at different levels of
      the neuraxis was examined in the rat. Behaviors organized at spinal (spinal motor
      reflexes, SMRs), medullary (vocalizations during shock, VDSs), and forebrain
      (vocalization afterdischarges, VADs) levels were elicited by noxious tailshock.
      Morphine administered into nPf generated dose-dependent increases in thresholds
      of VDS and VAD, but failed to elevate SMR thresholds. Increases in vocalization
      thresholds were reversed in a dose-dependent manner by the microinjection of the
      mu-opiate receptor antagonist, methylnaloxonium, into nPf. Results are discussed
      in terms of the relative influence of nPf-administered morphine on nociceptive
      processing at spinal versus supraspinal levels of the neuraxis.

PMID- 10936227
TI  - Evidence for cytochrome P4501A2-mediated protein covalent binding of
      thiabendazole and for its passive intestinal transport: use of human and rabbit
      derived cells.
AB  - Thiabendazole (TBZ), an anthelmintic and fungicide benzimidazole, was recently
      demonstrated to be extensively metabolized by cytochrome P450 (CYP) 1A2 in man
      and rabbit, yielding 5-hydroxythiabendazole (5OH-TBZ), the major metabolite
      furtherly conjugated, and two minor unidentified metabolites (M1 and M2). In this
      study, exposure of rabbit and human cells to 14C-TBZ was also shown to be
      associated with the appearance of radioactivity irreversibly bound to proteins.
      The nature of CYP isoforms involved in this covalent binding was investigated by
      using cultured rabbit hepatocytes treated or not with various CYP inducers
      (CYP1A1/2 by beta-naphthoflavone, CYP2B4 by phenobarbital, CYP3A6 by rifampicine,
      CYP4A by clofibrate) and human liver and bronchial CYP-expressing cells. The
      covalent binding to proteins was particularly increased in beta-naphthoflavone
      treated rabbit cells (2- to 4-fold over control) and human cells expressing
      CYP1A2 (22- to 42-fold over control). Thus, CYP1A2 is a major isoenzyme involved
      in the formation of TBZ-derived residues bound to protein. Furthermore, according
      to the good correlation between covalent binding and M1 or 5OH-TBZ production,
      TBZ would be firstly metabolized to 5OH-TBZ and subsequently converted to a
      chemically reactive metabolic intermediate binding to proteins. This metabolic
      activation could take place preferentially in liver and lung, the main
      biotransformation organs, rather than in intestines where TBZ was shown to be not
      metabolized. Moreover, TBZ was rapidly transported by passive diffusion through
      the human intestinal cells by comparison with the protein-bound residues which
      were not able to cross the intestinal barrier. Consequently, the absence of
      toxicity measured in intestines could be related to the low degree of TBZ
      metabolism and the lack of absorption of protein adducts. Nevertheless, caution
      is necessary in the use of TBZ concurrently with other drugs able to regulate
      CYP1A2, particularly in respect to liver and lung tissues, recognised as sites of
      covalent-binding.

PMID- 10936228
TI  - Autoantibody against oxidized low-density lipoproteins may be enhanced by
      cigarette smoking.
AB  - A total of 59 healthy male subjects (32 smokers and 27 nonsmokers) who had no
      reported systemic disease and did not take alcohol and vitamin supplementation
      were included. The levels of autoantibody to oxidized low-density lipoproteins
      (ox-LDL) in smokers and age-matched nonsmokers were compared. The plasma levels
      of antioxidants that can affect the formation of ox-LDL were also measured, and
      correlation analyses between anti ox-LDL IgG and plasma antioxidants, controlling
      for age and body mass index (BMI), were performed. Plasma alpha-tocopherol and
      uric acid concentrations of nonsmokers (2.78+/-1.09 microg/mg total lipid and
      6.96+/-1.69 mg/dl, respectively) were significantly higher than those of smokers
      (1.68+/-0.48 microg/mg total lipid and 6.15+/-1.14 mg/dl, respectively) (P<0.05).
      Although plasma ascorbate and retinol levels were not significantly different
      between smokers and nonsmokers, smokers older than 45 years old had significantly
      lower plasma ascorbate levels (0.32+/-0.17 mg/dl) than age-matched nonsmokers (0.
      53+/-0.14 mg/dl) (P=0.036). Higher level of plasma anti ox-LDL IgG was noted in
      the group of smokers compared with nonsmokers (515+/-409 mU/ml vs. 407+/-268
      mU/ml, respectively) under the statistic method of Chi-Square test (P=0.049). A
      significant negative correlation was found between plasma anti ox-LDL IgG and
      alpha-tocopherol in the combined population as well as in the smoker group (r=
      0.26, p=0.047; r=-0.48, p=0.006; respectively). However, there was no correlation
      between plasma anti ox-LDL IgG and the levels of other antioxidants. These
      results suggest that reduced concentrations of alpha-tocopherol are associated
      with cigarette smoking. The significantly negative correlation between plasma
      anti ox-LDL IgG and alpha-tocopherol in the entire study population as well as in
      the smoker group suggests that plasma alpha-tocopherol may be partially effective
      if not totally at protecting LDL from oxidative damage caused by cigarette
      smoking and dietary supplementation with alpha-tocopherol may provide a
      protective effect against LDL oxidation, especially in smokers.

PMID- 10936229
TI  - Lipid peroxidation, antioxidant enzymes, and benzo[a]pyrene-quinones in the blood
      of rats treated with benzo[a]pyrene.
AB  - The lipid peroxidation (as malondialdehyde, MDA), activities of superoxide
      dismutase (SOD) and catalase (CAT), and benzo[a]pyrene (BaP) metabolites were
      investigated in sera and erythrocytes of male Sprague-Dawley rats treated with
      BaP (20 mg per rat). MDA levels were significantly increased in sera (16.98+/
      3.29 nmol/ml serum, P<0.05) 12 h after BaP treatment and persisted up to 96 h
      (13.80+/-1. 65 nmol/ml serum, P<0.05), but no significant change in NIDA levels
      was observed in erythrocytes. SOD and CAT activities were significantly increased
      in erythrocytes shortly after BaP exposure, and they were slightly decreased in
      sera, indicating an inverse correlation between lipid peroxidation and
      antioxidant enzyme activity. BaP and BaP-quinones (BaP-1,6-quinone and BaP-3,6
      quinone) were measured in sera during the study period. A rapid increase of
      unmetabolized BaP was observed in sera (41.27+/-4.14 pmol/ml serum) 3 h after BaP
      treatment, reaching a peak at 6 h (48.56+/-4.62 pmol/ml serum) followed by a
      sharp decrease. Formation of the BaP-1, 6-quinone and BaP-3,6-quinone started in
      sera 3 h after BaP treatment, reached a peak at 24 h (7.23+/-1.02 pmol/ml serum)
      and 12 h (9.20+/-0.98 pmol/ml serum), respectively, and then decreased gradually.
      The time-dependent pattern of serum lipid peroxidation and the level of
      erythrocyte antioxidant enzymes were shown to be related to the concentrations of
      the BaP-quinone metabolites. These results suggest that BaP treatment, probably
      via the formation of BaP-quinones, oxidatively altered lipids and antioxidant
      enzymes in the blood, and might be associated with BaP-related vascular toxicity
      including carcinogenesis.

PMID- 10936230
TI  - Tyrosine as important contributor to the antioxidant capacity of seminal plasma.
AB  - A novel post-addition method, based on the trapping of ABTS-radicals, is applied
      for studying the total antioxidant capacity of seminal plasma. A remarkable
      profile is observed, in which seminal plasma quenches radicals in a continuous,
      relatively slow fashion. Five putative antioxidants present in seminal plasma
      were studied using the same assay. Some of the compounds such as ascorbic acid,
      alpha-tocopherol and uric acid exert immediate, fast radical trapping, whereas
      hypotaurine and tyrosine give rise to the same slow radical trapping curve as
      seminal plasma. Due to this slow, continuous radical trapping, quantification of
      the total antioxidant capacity (expressed as trolox equivalent antioxidant
      capacity, TEAC) strongly depends on the chosen time point after onset of radical
      trapping. When determined during the slow antioxidant trapping phase, tyrosine
      has a powerful antioxidant capacity, which in combination with its relatively
      high plasma concentration makes it an important contributor to the total
      antioxidant capacity of seminal plasma.

PMID- 10936232
TI  - Presidential address: why xenotransplantation?

PMID- 10936233
TI  - Opening address: welcome to nagoya(1)

PMID- 10936231
TI  - Genotoxic effects of allyl isothiocyanate (AITC) and phenethyl isothiocyanate
      (PEITC).
AB  - Two isothiocyanates (ITCs) commonly found in human diet, allyl isothiocyanate
      (AITC) and phenethyl isothiocyanate (PEITC), were tested for genotoxic effects in
      a battery of assays: Salmonella/microsome assay with TA 98 and TA 100,
      differential DNA repair assay with E. coli and micronucleus (MN) induction assay
      with human derived Hep G2 cells. Albeit to a different degree, both ITCs induced
      genotoxic effects in all test systems. AITC was more genotoxic in bacterial test
      systems than in Hep G2 cells; in contrast, the effect of PEITC was stronger in
      Hep G2 cells. In in vivo assays with E. coli indicators in which mice were
      exposed to relatively high doses of the compounds (90 and 270 mg/kg), AITC
      induced moderate but significant effects; PEITC failed to induce significant
      effects in any of the organs. To find out the reason for the weak genotoxicity of
      AITC and PEITC under in vivo test conditions, we exposed E. coli indicator cells
      to the test substances in the absence or presence of rat liver homogenate (with
      and without cofactors), bovine serum albumin (BSA) and human saliva. All of them
      markedly attenuated the genotoxicity of AITC and PEITC, implying that the test
      substances are detoxified by direct non-enzymatic binding to proteins. Additional
      experiments carried out on the mechanistic aspects of AITC and PEITC-induced
      genotoxicity showed that the compounds induce the formation of thiobarbituric
      acid reactive substances (TBARS) in Hep G2 cells. Furthermore, in in vitro assays
      with E. coli, radical scavengers reduced the differential DNA damage induced by
      AITC and PEITC. The latter two findings give a clue that reactive oxygen species
      might be involved in the genotoxic effect of the ITCs. Although ITCs have been
      repeatedly advocated as very promising anticancer agents, the data presented here
      indicate that the compounds are genotoxic, and probably carcinogenic, in their
      own right.

PMID- 10936234
TI  - Acute vascular rejection.

PMID- 10936235
TI  - Immunohistological study on the graft following all O- and xenotransplantation in
      recipients with preformed antibody.

PMID- 10936236
TI  - Differential expression of alpha-Gal epitopes on pig and mouse organs.

PMID- 10936237
TI  - Anti-galactose-alpha(1,3)Galactose antibody production in alpha1, 3
      galactosyltransferase gene knockout mice after xeno- and allotransplantation.

PMID- 10936238
TI  - Genes coding for anti-Gal in knock-out mice for the alpha1,
      3Galactosyltransferase gene: analysis by hybridomas.

PMID- 10936239
TI  - Ganglioside xenoantigens in pig lymphocytes and aorta.

PMID- 10936240
TI  - Identification of non-alphaGal xenoantigens on porcine red blood cells.

PMID- 10936241
TI  - Effect of various glycosyltransferases on the swine xenoantigen.

PMID- 10936242
TI  - In vitro and in vivo inhibition of anti-gal secreting cells.

PMID- 10936243
TI  - Identification of B cells with receptors for alpha-Gal epitopes (Galalpha 1
      3Galbeta1-4GlcNac-R) in xenograft recipients.

PMID- 10936244
TI  - Recombinant Galalpha1,3Gal-substituted mucin/immunoglobulin chimeras: a superior
      absorber of anti-pig antibodies.

PMID- 10936245
TI  - Plasma perfusion by apheresis through a gal immunoaffinity column successfully
      depletes anti-Gal antibody: experience with 275 aphereses in baboons.

PMID- 10936246
TI  - Absence of cross-reactivity between xenoantibodies directed against concordant or
      discordant xenoantigens in rats.

PMID- 10936247
TI  - A simple and sensitive quantitative method for determining xenoreactive antibody
      titers in the mouse-to-rat cardiac transplantation model.

PMID- 10936249
TI  - Analysis of antiporcine antibodies in cynomolgus recipients of porcine kidneys on
      cyclophosphamide-based immunosuppression.

PMID- 10936248
TI  - Prolonged survival of guinea-pig-to-rat heart xenografts following complement
      depletion and B-cell-directed immunosuppression by malononitrilamide.

PMID- 10936250
TI  - Development of a donor-specific, automated, and cost-effective cytotoxicity assay
      for human serum on primary porcine cells.

PMID- 10936251
TI  - Xenoreactivity of fetal and neonatal baboon intracellular antibody against the
      pig.

PMID- 10936252
TI  - Human natural antibodies that recognize nonalphaGal antigens on porcine red blood
      cells.

PMID- 10936253
TI  - Immunogenicity of Hanganutziu-Deicher antigens in pig-to-human
      xenotransplantation.

PMID- 10936254
TI  - Xenoantigenacity of Chinese Neijiang pig-related to xenotransplantation.

PMID- 10936255
TI  - alpha-Gal and beta-Gal are preferentially expressed on porcine cardiac
      microvascular endothelium.

PMID- 10936256
TI  - Comparison of immunoadsorption by GAL-alpha 1,3- gal-paa disaccharide columns and
      by extracorporeal kidney perfusion in the setting of discordant xenogeneic lung
      transplantation.

PMID- 10936257
TI  - Natural anti-Gal antibodies constitute 0.2% of intravenous immunoglobulin and are
      equally retained on a synthetic disaccharide column or on an immobilized natural
      glycoprotein.

PMID- 10936259
TI  - Human serum induces apoptosis of isolated mouse cardiomyocytes in vitro.

PMID- 10936258
TI  - Removal of terminal alpha-galactosyl residues by endo-beta-galactosidase C, a
      potent endoglycosidase which acts under physiological pH conditions.

PMID- 10936260
TI  - Neutralization of anti-alphaGalactosyl antibodies without immunosuppression
      prevents hyperacute rejection but not acute vascular rejection of pig organs
      transplanted into baboons.

PMID- 10936261
TI  - Augmented anti-alphaGalactosyl antibodies in adult baboons in the setting of
      intestinal parasitic infections are not associated with higher titers of anti-pig
      hemolytic antibody.

PMID- 10936262
TI  - Efficiency of transgenesis using sperm-mediated gene transfer: generation of hDAF
      transgenic pigs.

PMID- 10936263
TI  - hDAF expression in hearts of transgenic pigs obtained by sperm-mediated gene
      transfer.

PMID- 10936264
TI  - Modulation of fluid-phase complement activation inhibits hyperacute rejection in
      a porcine-to-human xenograft model.

PMID- 10936265
TI  - A surface-bound form of human C1 esterase inhibitor on xenografts: the complement
      regulatory function.

PMID- 10936266
TI  - Relative roles of hCD46 and hCD55 in the regulation of hyperacute rejection.

PMID- 10936267
TI  - Prevention of hyperacute rejection by phosphatidylinositol-anchored factor I.

PMID- 10936269
TI  - Adenovirus-mediated gene transfer of double human complement regulating proteins
      (DAF, CD59) in xenogeneic rat kidney perfusion.

PMID- 10936268
TI  - Effect of adenovirus-mediated gene transfer with 5I2 gene in guinea pig-to-rat
      xenotransplantation.

PMID- 10936270
TI  - Effects of the endothelin-1 receptor antagonist TAK-044 on pulmonary injury in
      discordant xenotransplantation.

PMID- 10936271
TI  - Successful generation of transgenic pigs for human decay-accelerating factor and
      human leucocyte antigen DQ.

PMID- 10936272
TI  - Human CD46 rather than CD55 is a key element in protection against complement
      activation in vitro.

PMID- 10936273
TI  - T cells interacting with the alpha-Gal epitope: studies in alpha1,
      3Galactosyltransferase knock-out mice.

PMID- 10936274
TI  - T cell repertoire alterations in allograft and xenograft rejection processes.

PMID- 10936275
TI  - Inhibition of human anti-pig T cell response by anti-CD2, anti-CD40L, and CTLA4
      Ig: a comparative study.

PMID- 10936276
TI  - Human monocytes bind to two distinct carbohydrate capping structures on porcine
      endothelium.

PMID- 10936277
TI  - Human natural killer cells augment B cell responses to porcine xenoantigens.

PMID- 10936278
TI  - Effect of the remodeling of a glycoantigen on natural killer cell-mediated direct
      cytotoxicity.

PMID- 10936279
TI  - Human monocytes bind to ligands on porcine endothelium containing the gal alpha
      (1,3)-Gal antigen.

PMID- 10936280
TI  - Analysis of granzyme B and caspases pathway in xenogeneic cytotoxicity.

PMID- 10936281
TI  - Complement- and xenoantibody-independent discordant xenograft rejection in a
      guinea pig to rat model.

PMID- 10936282
TI  - Identification, detection, and in vitro characterization of cynomolgus monkey
      natural killer cells in delayed xenograft rejection of hDAF transgenic porcine
      renal xenografts.

PMID- 10936283
TI  - HLA-G inhibits the transendothelial cell migration of human NK cells: a strategy
      for inhibiting xenograft rejection.

PMID- 10936284
TI  - Protection against natural killer-mediated swine endothelial cell lysis by HLA-G
      and HLA-E.

PMID- 10936285
TI  - Bcl-2 expression in pig cells suppresses the apoptosis caused by human
      perforin/granzymes- or FasL/Fas-mediated cytotoxicity.

PMID- 10936286
TI  - Avoidance of graft versus host disease by proper titration of cell and radiation
      dose in a mouse to rat xeno-chimera.

PMID- 10936287
TI  - Inhibitory effect of cathepsin B inhibitor CA 074 on mouse anti-rat mixed
      lymphocyte reaction: novel immunosuppressive strategy for indirect xenoantigen
      recognition.

PMID- 10936288
TI  - Structural analysis of hyperacute rejection in cardiac xenotransplantation:
      comparison of two different donor-recipient species combinations.

PMID- 10936289
TI  - Modification of antigen-presenting cell functions by heparan sulfate.

PMID- 10936290
TI  - Cellular adhesion and proliferative responses of neonatal human lymphocytes to
      pig endothelial cells.

PMID- 10936291
TI  - Human T-cell receptor variable gene analysis against porcine peripheral
      lymphocytes.

PMID- 10936292
TI  - The role of human T cells in human anti-pig xenogeneic cellular responses.

PMID- 10936293
TI  - Allosensitization increases human anti-pig cellular xenoreactivity.

PMID- 10936294
TI  - Transplantation of xenogeneic embryonic thymus to athymic nude mice induces
      acquisition of distorted immunity.

PMID- 10936295
TI  - Macrophages as an effector mechanism to reject encapsulated hepatoma cells.

PMID- 10936296
TI  - Immunohistochemical study of a new experimental model of acute cellular xenograft
      rejection.

PMID- 10936297
TI  - Induction of human T-cell proliferation by porcine fetal brain cells: role of
      astrocytes and macrophages/microglia.

PMID- 10936298
TI  - Effect of M-CSF, GM-CSF in adenovirus-mediated gene transfer into macrophages.

PMID- 10936299
TI  - Histologic comparison of small bowel, heart, and kidney xenografts in a rat to
      mouse model.

PMID- 10936300
TI  - Absence of hyperacute rejection and preservation of function in HDAF transgenic
      pig kidneys exposed to prolonged cold ischaemia.

PMID- 10936301
TI  - CD39/vascular ATP diphosphohydrolase modulates xenograft survival.

PMID- 10936302
TI  - Induction of tissue factor mRNA in acute vascular rejection: localization by in
      situ reverse transcriptase polymerase chain reaction.

PMID- 10936303
TI  - Regulated endothelial cell expression of novel anticoagulants: a strategy for the
      prevention and therapy of intravascular thrombosis.

PMID- 10936304
TI  - Platelet heparanase in vascular responses to xenotransplantation.

PMID- 10936305
TI  - Apoptosis in acute vascular rejection of xenografts.

PMID- 10936306
TI  - Biochemical basis for induction of resistance to human complement in porcine
      endothelial cells by alphaGAL ligation.

PMID- 10936307
TI  - alphaGAL ligation with a lectin induces activation and resistance to the
      proinflammatory effects of human complement on porcine endothelium.

PMID- 10936308
TI  - Induction of accommodation in the hamster-to-rat model requires inhibition of the
      membrane attack complex of complement.

PMID- 10936309
TI  - Identification and characterization of novel porcine molecules specifically
      regulated on endothelial cells by human complement activation.

PMID- 10936310
TI  - The major surface-labeled alpha-galactosylated glycoprotein of pig endothelial
      cells is the beta1 integrin subunit.

PMID- 10936311
TI  - Fluorescence scanner assay for detecting distribution of carbohydrates on porcine
      endothelial cell.

PMID- 10936312
TI  - Effect of extra cellular matrix in adenovirus-mediated gene transfer into
      endothelial cells.

PMID- 10936313
TI  - Expression of monocyte chemoattractant protein 1 in pig-to-primate cardiac
      xenografts.

PMID- 10936314
TI  - Hepatocyte growth factor and vascular endothelial growth factor expression in pig
      to-primate xenotransplanted hearts.

PMID- 10936315
TI  - Von willebrand factor concentration, multimeric patterns, and cleaving protease
      activity in baboons undergoing xenogeneic peripheral blood stem cell
      transplantation.

PMID- 10936316
TI  - Differential immune response to carbohydrate epitopes on allo- and xenografts:
      implications for accommodation.

PMID- 10936317
TI  - Surrogate tolerogenesis: possible pretransplant induction of accommodation of pig
      xenografts.

PMID- 10936318
TI  - Altered expression of matrix metalloproteinases in pig-to-primate
      xenotransplanted hearts.

PMID- 10936319
TI  - Analysis of cardiac function during hyperacute rejection: effects of PAF
      antagonist, TXA(2) inhibitor/antagonists, and nitroglycerin.

PMID- 10936320
TI  - Efficacy of FK506, leflunomide, anti-CD4, and CTLA4IG treatments in rat to mouse
      pancreas xenograft transplantation.

PMID- 10936321
TI  - Nondepleting anti-CD4 but not anti-CD8 antibody induces long-term survival of
      xenogeneic and allogeneic hearts in alpha1, 3-galactosyl-transferase knock-out
      mice.

PMID- 10936322
TI  - Costimulatory signal blockade by anti-CD2 monoclonal antibody in combination with
      15-deoxyspergualin prolongs concordant xenograft survival.

PMID- 10936324
TI  - Effects of pretransplant splenectomy and immunosuppression of humoral immunity in
      a pig-to-newborn goat cardiac xenograft model.

PMID- 10936323
TI  - Effect of B cell/plasma cell depletion or suppression on anti-Gal antibody in the
      baboon.

PMID- 10936325
TI  - Cyclosporine induces long-term xenograft survival in the mouse-to-C6-deficient
      rat heart transplantation model.

PMID- 10936326
TI  - Macrophage depletion prevents accelerated rejection and results in long-term
      survival in hamster to rat cardiac xenotransplantation.

PMID- 10936327
TI  - FTY720 in combination with CsA inhibits islet xenograft rejection: a study in the
      pig-to-rat model.

PMID- 10936328
TI  - WF10 in xenotransplantation-a potential new approach.

PMID- 10936329
TI  - Simple therapy for cardiac concordant xenotransplantation: only 1 week of DSG
      administration with suppression of t-cell reactions.

PMID- 10936330
TI  - Does adenovirus-mediated viral IL-10 gene transfer prolong survival of xenogeneic
      spheroidal aggregate-cultured hepatocytes?

PMID- 10936331
TI  - Efficacy of malononitriloamide 279 and 715 in islet xenotransplantation: a study
      in the pig-to-rat model.

PMID- 10936332
TI  - Protective effect of FK-506 in pig-to-rat islet xenotransplantation is abrogated
      by prednisolone.

PMID- 10936333
TI  - Brequinar in combination with cyclosporine a inhibits islet xenograft rejection
      for up to 24 days: a study in the pig-to-rat model.

PMID- 10936335
TI  - Induction of combined T-cell-dependent and T-cell-independent xenograft tolerance
      by thymus/heart composite grafts.

PMID- 10936334
TI  - Multilineage bone marrow chimerism produces cellular and humoral tolerance in a
      mouse-to-rat cardiac xenograft.

PMID- 10936337
TI  - Blood transfusion effect on xenograft survival in athymic nude rats is mediated
      by humoral factors.

PMID- 10936336
TI  - Administration of CTLA4-Ig enhances the incidence of hamster-to-rat xenogeneic
      bone marrow engraftment and alters the presentation of graft-vs-host disease.

PMID- 10936338
TI  - Oral delivery of xenoantigen combined with non-depleting anti-CD4 monoclonal
      antibody induced significant prolonged survival of concordant skin xenografts.

PMID- 10936339
TI  - Xenogeneic humoral graft-Vs-host disease following hamster-to-Rat bone marrow
      transplantation.

PMID- 10936340
TI  - Synergistic effect of pretransplant xenogeneic blood transfusion with NK cell
      and/or B-cell immunosuppression to modulate T-cell-independent xenoreactivity.

PMID- 10936341
TI  - Partial deletion of donor T cells in the recipient thymus in fully xenogeneic
      mouse-to-rat chimeras.

PMID- 10936342
TI  - Human parathyroid grafts survived and functioned in mice treated with anti-CD4
      monoclonal antibody.

PMID- 10936343
TI  - Targeted transgene expression using the human HLA-DRA promoter in a retroviral
      vector.

PMID- 10936344
TI  - In vitro differentiation of human lymphocytes in a porcine microenvironment:
      implication for xenogeneic organ transplantation.

PMID- 10936345
TI  - Increases in autologous hematopoietic progenitors in the blood of baboons
      following irradiation and treatment with porcine stem cell factor and interleukin
      3.

PMID- 10936346
TI  - Porcine stem cell factor facilitates long-lasting porcine hematopoietic
      engraftment in murine recipients.

PMID- 10936347
TI  - Experience with porcine thymic transplantation in baboons.

PMID- 10936348
TI  - Probable failure of chimerism induction in orthotopically transplanted monkey
      hearts in baboons.

PMID- 10936349
TI  - An attempt to induce peripheral tolerance in a pig-to-primate transplantation
      model by infusion of ultrahigh numbers of donor peripheral blood mononuclear
      cells: first promising results.

PMID- 10936350
TI  - VLA-Integrin beta-1 chain function is not fully conserved between the human and
      porcine species: implications for xenotransplantation.

PMID- 10936351
TI  - A novel model mimicking the immunoreactivity in pig-to-human xenotransplantation.

PMID- 10936352
TI  - RYR1 genotype of the Chinese Neijiang pig.

PMID- 10936353
TI  - Diabetic rats transplanted with adult porcine islets and immunosuppressed with
      cyclosporine, mycophenolate mofetil, and leflunomide remain normoglycemic for up
      to 100 days.

PMID- 10936354
TI  - Murine chemokine gene expression in rejecting pig proislet xenografts.

PMID- 10936355
TI  - Ultrastructural identification of cells expressing Galalpha1-3Gal antigen in
      cultured fetal porcine isletlike cell clusters.

PMID- 10936356
TI  - Xenografting of pig islets in monkeys does not result in hyperacute rejection.

PMID- 10936357
TI  - Porcine islets of langerhans isolated from normal and hDAF transgenic pigs elicit
      the same acute inflammatory reaction during exposure to human blood; inhibition
      of the response with soluble complement receptor 1 and heparin.

PMID- 10936358
TI  - Complement regulatory proteins on human and porcine nontransgenic and hDAF
      transgenic islet cells: expression and role in susceptibility to lysis by human
      serum.

PMID- 10936359
TI  - Avipox virus vectors for gene delivery to fetal mouse and pig proislets.

PMID- 10936360
TI  - Xenographic survival and function of transplanted monkey pancreatic islets in
      rats.

PMID- 10936361
TI  - Role of macrophages and natural killer cells in the rejection of pig islet
      xenografts in mice.

PMID- 10936362
TI  - Pig-to-rabbit islet transplantation as an immunologic model of pig-to-human islet
      xenografts.

PMID- 10936364
TI  - Beneficial effects of pentoxiphylline on islet transplantation.

PMID- 10936363
TI  - Efficacy of agarose/polystyrene sulfonic acid microencapsulation for islet
      xenotransplantation.

PMID- 10936365
TI  - Role of nonimmunological factors in islet graft failure.

PMID- 10936367
TI  - Transendothelial migration and infiltration of porcine xenografts by primate
      monocytes requires natural killer cell-dependent activation.

PMID- 10936366
TI  - The role of species barrier on the development of pericapsular neogrowth of
      encapsulated islets.

PMID- 10936368
TI  - Delayed cardiac xenograft rejection in a pig-to-baboon model treated with a
      tolerance-inducing regimen and donor bone marrow infusion.

PMID- 10936369
TI  - Perioperative monitoring of cardiac function during discordant pig-to-primate
      kidney xenotransplantation using transpulmonary thermodilution.

PMID- 10936370
TI  - Technique of immunoapheresis in heterotopic and orthotopic xenotransplantation of
      pig hearts into cynomolgus and rhesus monkeys.

PMID- 10936371
TI  - Expression of the transcriptional factor egr-1/BTEB2 in cardiac xenograft
      vascular remodeling.

PMID- 10936372
TI  - Nonmuscle myosin heavy chain and nuclear factor-kappa B expression in pig-to
      primate xenotransplanted hearts.

PMID- 10936373
TI  - Long-term survival of cynomolgus monkeys following pig-to-primate kidney
      xenotransplantation using h-DAF transgenic donor organs.

PMID- 10936374
TI  - Comparative study of antibody removal before pig-to-baboon and human ABO
      incompatible renal transplantation.

PMID- 10936375
TI  - Factors determining the onset of hyperacute rejection following discordant
      porcine-to-cynomolgus monkey kidney xenotransplantation.

PMID- 10936376
TI  - Coagulation/thrombotic disorders associated with organ and cell
      xenotransplantation.

PMID- 10936377
TI  - A nonmyeloablative regimen with CD40L blockade leads to humoral and cellular
      hyporesponsiveness to pig hematopoietic cells in baboons.

PMID- 10936378
TI  - Induction of mixed hematopoietic chimerism in the pig-to-baboon model.

PMID- 10936379
TI  - Injection of porcine anti-idiotypic antibodies to primate anti-Gal antibodies
      leads to active inhibition of serum cytotoxicity in a baboon.

PMID- 10936380
TI  - Human-pig spleen transplantation leading to high level of chimerism.

PMID- 10936381
TI  - Preparation of bioartificial liver using hollow fibers with four different cut
      off molecular weights.

PMID- 10936382
TI  - Concordant hamster-to-rat liver xenotransplantation leads to hyperlipidemia.

PMID- 10936383
TI  - Loss of serum bicarbonate after discordant liver xenotransplantation.

PMID- 10936384
TI  - Attenuation of hepatic microcirculatory failure during in situ xenogeneic rat
      liver perfusion by heat shock preconditioning.

PMID- 10936385
TI  - The porcine liver supports metabolic homeostasis in the nonhuman primate:
      experimental study in a model of orthotopic liver transplantation from h-DAF
      transgenic pig to baboon.

PMID- 10936386
TI  - Acute liver failure attenuates hyperacute xenograft rejection.

PMID- 10936387
TI  - Adenovirus-mediated gene transfer of the triple human complement regulating
      proteins (DAF, CD59, MCP) in xenogeneic pig liver perfusion.

PMID- 10936388
TI  - Intraperitoneal transplantation of microencapsulated xenogeneic hepatocytes in
      totally hepatectomized rats.

PMID- 10936389
TI  - Establishment of a reversibly immortalized human hepatocyte cell line by using
      Cre/loxP site-specific recombination.

PMID- 10936390
TI  - Xenotransplantation of immortalized human hepatocytes for experimental acute
      liver failure in rats.

PMID- 10936391
TI  - Three-stage total hepatectomy using a portocaval shunt tube in rats.

PMID- 10936392
TI  - Rearterialization of hepatic xenografts in the combination of hamster-to-rat.

PMID- 10936393
TI  - Analysis of hyperacute rejection in newborn pig-to-dog lung xenotransplantation.

PMID- 10936394
TI  - Evidence of immunocomplex formation in pulmonary xenografts.

PMID- 10936395
TI  - Xeno ex vivo perfusion model in immature and mature porcine lung with human red
      blood cells and serum.

PMID- 10936397
TI  - Nonmuscle myosin heavy chain and metalloproteinase-2 expression in concordant
      pulmonary xenografts.

PMID- 10936396
TI  - Ex vivo perfusion of swine lungs: lung function in a pig-to-human model of
      xenotransplantation.

PMID- 10936398
TI  - Potential risk of xenotransplant-associated infections.

PMID- 10936399
TI  - Transmission of pig endogenous retrovirus to primary human cells.

PMID- 10936400
TI  - Molecularly cloned porcine endogenous retroviruses replicate on human cells.

PMID- 10936401
TI  - Porcine endogenous retrovirus is not transmitted in a discordant porcine-to
      cynomolgus xenokidney transplantation model with long-term survival of organ
      recipients.

PMID- 10936402
TI  - Analysis of potential porcine endogenous retrovirus transmission to baboon in
      vitro and in vivo.

PMID- 10936403
TI  - Investigations on biological safety and immunologic aspects of chimeric
      bioartificial vessels in xenotransplantation.

PMID- 10936404
TI  - Porcine endogenous retroviruses: diagnostic assays and evidence for
      immunosuppressive properties.

PMID- 10936405
TI  - Current applications of cellular xenografts.

PMID- 10936406
TI  - Xenotransplantation and animal welfare.

PMID- 10936407
TI  - Neural tissue xenografting in neurodegenerative disorders: countdown to a
      clinical trial.

PMID- 10936408
TI  - Attitudes to xenotransplantation: interviews with patients suffering from
      parkinson's disease focusing on the conception of risk.

PMID- 10936409
TI  - Future of xenotransplantation: what are the ethical problems?

PMID- 10936411
TI  - Prostaglandins and fatty acids regulate transcriptional signaling via the
      peroxisome proliferator activated receptor nuclear receptors.

PMID- 10936412
TI  - The nature and composition of 15-deoxy-Delta(12,14)PGJ(2).

PMID- 10936413
TI  - 15-deoxy-Delta(12,14)PGJ(2) induces diverse biological responses via PPARgamma
      activation in cancer cells.

PMID- 10936414
TI  - COX-2 and the cyclopentenone prostaglandins - a new chapter in the book of
      inflammation?

PMID- 10936415
TI  - PPARgamma: observations in the hematopoietic system.
AB  - Human Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) was originally
      cloned from a human bone marrow library. What role does this ligand activated
      transcription factor play in hematopoiesis and the immune system? We note that:
      a) PPARgamma has potential to interact/interfere or synergize with retinoid
      biology, b) fatty acids and a prostaglandin have been identified as ligands, and
      c) lymphocytes, monocytes and neutrophils use fatty acids as a major source of
      energy production, d) PPARgamma has been shown to oppose TNFalpha and down
      regulate cytokine production in monocytes. Therefore, we undertook a review of
      the literature and an expression survey of PPARgamma in a number of major organs
      and cells involved in the hematopoietic system, for the purpose of building a
      database towards understanding the role and function of PPARgamma gene regulation
      in the developing blood and immune systems. PPARgamma is expressed before
      mesodermal induction in tissue in and around Speymann's organizer in the xenopus
      blastocyst, in erythroid precursors of blood islands and in the circulation of
      the day 10.0 murine embryo, in human 19 week fetal liver, in some but not all
      murine and human bone marrow erythroid, myeloid, and monocytoid progenitors, bone
      marrow stromal cells and adipocytes, osteoblasts, endothelial cells, some T, and
      B lymphocytes, monocytes, macrophages, and other monocytic derivatives. It can be
      found in the cells of Peyer's patches, lymphoid follicles, spleen, and thymus. It
      is not clear if it is ever or transiently expressed in megakaryocytes, mast
      cells, or neutrophils. Based on the above data and a review of the literature,
      PPARgamma seems to play a role during the elicitation of immune responses. We
      propose PPARgamma may be involved in changes in energy states required during
      activation and development of many cell types involved, and has additional
      immunologically relevant effects in erythroid, myeloid, monocytic, T and B
      lymphocytic, stromal, and endothelial cell function.

PMID- 10936416
TI  - The effects of Delta(12)-PGJ(2) on malignant cells.

PMID- 10936417
TI  - Peer review

PMID- 10936418
TI  - Dyshaemopoiesis in adults: a practical classification for diagnosis and
      management.
AB  - Dyshaemopoiesis is a heterogeneous disease that may be classified into non-clonal
      and clonal dyshaemopoiesis. Non-clonal dyshaemopoiesis comprises reversible
      disorders with DNA synthesis impairment in dividing cells of the bone marrow by
      avitaminosis through various mechanisms or direct DNA damage from multiple
      causes. Complete haematologic recovery is obtained after vitamin supplementation
      or suppression of a myelotoxic agent. On the contrary, clonal dyshaemopoiesis is
      a group of chronic and usually irreversible diseases that may culminate in acute
      leukaemia (AL). These so called myelodysplastic syndromes (MDS) and their
      variants may be classified as primary, secondary and other diseases with doubtful
      clonality. A detailed classification of dyshaemopoiesis in adults may offer
      partial help in the diagnosis and management of dyshaemopoiesis. Pathobiological
      studies in progress allow better understanding of MDS and consequently the
      establishment of new modalities of treatment.

PMID- 10936420
TI  - Decreased chronic lymphocytic leukemia incidence in Asians in Los Angeles County.
AB  - Chronic lymphocytic leukemia (CLL) is rare in Asians living in Asia and possibly
      in US Asians. In contrast, CLL is the most common leukemia in whites. The basis
      for this ethnic and geographic variation is unknown. We compared average annual
      age-adjusted incidence rates (AAIR) of CLL diagnosed from 1972 to 1995 among Los
      Angeles County-resident Asians, non-Spanish-surnamed- and Spanish-surnamed whites
      (non-Hispanic and Hispanic-whites) and blacks using the University Southern
      California-Cancer Surveillance Program (USC-CSP), the population-based cancer
      registry for Los Angeles County. Asian groups studied included Chinese, Japanese,
      Filipinos and Koreans. Expected numbers of CLL cases were based on the age
      adjusted incidence rates in non-Hispanic whites and compared to numbers of cases
      observed in Chinese, Japanese and Filipinos. Possible association of
      socioeconomic state (SES) was assessed using AAIRs with SES-specific
      denominators. In the absence of denominators by birthplace, the association of
      birthplace and CLL-incidence was evaluated using proportional odds ratios (POR).
      Los Angeles County Asian males and females had significantly lower AAIRs than non
      Hispanic whites (males: AAIR=0.7 per 100000 population, 95% confidence interval
      (CI), 0.5-1.0 vs. 4.4, 95% CI, 4.3-4.6; and females: AAIR=0.5, 95% CI, 0.3-0.7
      vs. 2.3, 95% CI, 2.2-2.4). Fewer Japanese Chinese and Filipinos were diagnosed
      with CLL than expected (P<0.01). There was no association of birthplace (POR=0.9,
      95% CI, 0. 5-1.9) or SES on CLL-risk. CLL-risk was markedly lower in Los Angeles
      County Asians compared to non-Hispanic whites. Neither birthplace nor
      socioeconomic state accounted for this difference suggesting a role for genetic
      or other environmental factors in decreasing CLL-risk.

PMID- 10936419
TI  - Hematopoietic stem cell transplantation in patients with myelodysplastic
      syndrome.
AB  - Myelodysplastic syndrome (MDS) is a stem cell disorder, and hematopoietic stem
      cell transplantation is currently the only therapeutic modality that is
      potentially curative. Among patients with less advanced MDS (<5% marrow blasts),
      3-year survivals of 65-70% are achievable with HLA-identical related and HLA
      matched unrelated donors. The overall probability of disease recurrence in these
      patients is <5%. Among patients with advanced disease (>/=5% marrow blasts),
      about 35-45% and 25-30%, respectively, are surviving in remission after
      transplantation from a related or from an unrelated donor; the incidence of post
      transplant relapse is 10-35%. The criteria proposed by the International
      Prognostic Scoring System (IPSS) derived from non-transplanted patients, also
      predict survival following transplantation. The development of new conditioning
      regimens has permitted successful hematopoietic stem cell transplants even in
      patients more than 60 years of age. Improved survival with transplants from
      unrelated volunteer donors may, in part, reflect selection of donors on the basis
      of high resolution (allele-level) HLA typing. Autologous stem cell
      transplantation may be beneficial for selected patients who have obtained a
      complete remission with conventional chemotherapy. Treatment-related morbidity
      and mortality, in particular after allogeneic transplantation, remain challenges
      that need to be addressed with innovative approaches.

PMID- 10936422
TI  - Malignant hematopoietic cell lines: in vitro models for the study of multiple
      myeloma and plasma cell leukemia.
AB  - Multiple myeloma (MM) is a neoplasm of a terminally differentiated B-cell. The
      disease is progressive and always lethal characterized by the slow proliferation
      of malignant plasma cells in the bone marrow. Much of our current understanding
      of the biology of MM has been obtained by studying MM-derived cell lines. Human
      myeloma cell lines were shown to be suitable model systems for use in various
      fields of the biological sciences. However, it has proved very difficult to
      establish cell lines from plasma cell dyscrasias. Most reported MM cell lines
      have been derived from patients with advanced disease and from extramedullary
      sites. Nevertheless, within the last 20 years more than 100 cell lines have been
      established. A significant portion of this panel is partially or well
      characterized with regard to their cell culture, clinical, immunophenotypic,
      cytogenetic and functional features. Distinct immunoprofiles could be assigned to
      MM cell lines. All MM cell lines display chromosomal aberrations; in more than
      80% of the cell lines analyzed, chromosome 14 band q32 (immunoglobulin heavy
      chain locus) is affected; the various types of 14q+ chromosomes showed different
      distributions among the MM cell lines. A large percentage of MM cell lines is
      constitutively interleukin-6-dependent or responsive to various cytokines. It is
      important to realize that not every cell line established from a patient with
      myeloma is a neoplastic cell line. So-called 'myeloma cell lines' have been
      previously reported and are still widely used which are in reality Epstein-Barr
      virus (EBV)-positive B-lymphoblastoid cell lines. The presence of the EBV-genome
      in residual normal B-cells provides them with a selective growth advantage after
      explantation. In summary, a significant number of authentic and well
      characterized MM cell lines has been established and described. The availability
      of these bona fide MM cell lines is of great importance for the study of the
      biology, etiology and treatment of the disease.

PMID- 10936421
TI  - Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high
      dose cytarabine/mitoxantrone/ethyol @ (Amifostine).
AB  - Twenty patients with poor prognosis AML and four patients in the blastic phase of
      a myeloproliferative disorder were treated with two 'pulses' of therapy each
      consisting of two doses of high dose araC (separated by 12 h) followed by a
      single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was
      then administered tiw. The median age of the population was 68 years with 88% of
      patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia
      of 58% of patients either entered a CR or reverted to preleukemic state. For
      patients under 70 years of age, treatment produced 62% CRs with a leukemia free
      decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36%
      of patients having a leukemia free decision marrow.

PMID- 10936423
TI  - B cell lymphomas of C57L/J mice; the role of natural killer cells and T helper
      cells in lymphoma development and growth.
AB  - The Hodgkin's-like Type B neoplasms which arise spontaneously in aging C57L mice
      (25% incidence at 21 months of age) were first reported over 40 years ago, but
      since then relatively little has been published about these lymphomas. Based on
      previous studies in SJL mice, we investigated the phenotypic and functional
      properties of C57L-derived lymphomas in relation to Mtv29-encoded vSAg expression
      by the tumor cells, and their ability to stimulate TCR Vbeta-restricted T cells.
      The cell surface phenotype of the C57L lymphomas indicates a B cell origin
      (sIg(+), MHC II(+)). These B lymphoma cells also express co-stimulatory molecules
      [B7-1 (CD80) and HSA (CD24)], and stimulate marked proliferation of syngeneic
      CD4(+) T cells. C57L B lymphoma cells exhibit Mtv-encoded mRNA by northern
      analysis, and also stimulate IL-2 production from Vbeta16(+) T cell hybrids,
      suggesting a role for Mtv 29 in this syngeneic T cell response. After transfer to
      syngeneic recipients, primary C57L lymphomas grow slowly, if at all. However,
      tumor growth is greatly accelerated by pretreatment of C57L recipients with anti
      asialo GM1 antibody (but not anti-CD8 mAb), suggesting that NK cells play a major
      role in inhibiting lymphoma growth. If, in addition to anti-asialo GM1, the mice
      are also pretreated with anti-CD4 mAb, tumor growth is markedly inhibited,
      indicating that the lymphoma-responsive syngeneic CD4(+) T cells promote tumor
      growth. Therefore, although the vSAg-induced response stimulated by vSAg29
      expressing lymphoma cells in syngeneic TCR Vbeta-restricted CD4(+) T cells is an
      important etiologic factor in this type of B cell neoplasm both in C57L and in
      SJL mice, the final outcome of the spontaneous neoplastic process appears
      strongly influenced by endogenous NK activity in aging mice.

PMID- 10936424
TI  - Genomic organisation and expression of BCL6 in murine B-cell lymphomas.
AB  - BCL6 encodes a transcription factor deregulated by chromosomal translocations in
      human diffuse large cell B lymphomas (DLCL). This study was designed to determine
      whether Bcl6 might also be involved in lymphomas of mice. BCL6 protein was
      expressed at high levels in 90% or more of DLCL but not in low grade B lymphomas.
      Southern hybridisation studies demonstrated altered organisation of Bcl6 in three
      primary DLCL and the WEHI 231 B-cell lymphoma cell line but not in low grade
      tumours. Chromosomal painting and fluorescence in situ hybridisation (FISH)
      analyses of the WEHI 231 metaphase spreads revealed a T(5;16) translocation with
      Bcl6 on Chromosome 16 at the translocation breakpoint. Deregulated expression of
      BCL6 is thus likely to contribute to the genesis of DLCL of mice as well as of
      humans.

PMID- 10936425
TI  - Extramedullary blast crisis in a patient with chronic myelogenous leukemia in
      complete cytogenetic and molecular remission on interferon-alpha therapy.
AB  - We report the previously undescribed occurrence of extramedullary blast crisis in
      a patient with chronic myelogenous leukemia in complete cytogenetic and molecular
      remission on interferon-alpha. Development of bilateral testicular swelling
      prompted a biopsy showing stromal infiltration with CD20 and TdT positive
      immature cells. On repeated examinations, the bone marrow remained BCR/ABL
      negative by RT-PCR analysis. However, the cerebrospinal fluid (CSF) contained
      atypical lymphocytes positive for the P210 BCR-ABL product. Following treatment
      with testicular irradiation, intrathecal methotrexate, systemic chemotherapy and
      an unrelated donor transplant, the patient showed no evidence of disease until 9
      months post-transplant, when he relapsed in lymphoid blast crisis in both bone
      marrow and CSF.

PMID- 10936426
TI  - Determination of the in vivo loading of the lumbar spine with a new approach
      directly at the workplace--first results for nurses.
AB  - OBJECTIVE: To determine the magnitude of workplace loading for nurses with and
      without a history of low back pain. DESIGN: A measurement system for the
      assessment of workplace loading as well as a model for the calculation of lumbo
      sacral junction loading was designed and applied to a group of 12 nurses with and
      without a history of low back pain. BACKGROUND: Disagreement exists regarding the
      key factors in the aetiology of low back pain. Traditionally workplace loading is
      viewed as the dominant influence. Data for workplace loading in jobs with non
      uniform tasks, however, do rarely exist. METHODS: A three-dimensional inverse
      dynamic and force distribution model as well as the respective data acquisition
      system was used to assess the workplace loading of 12 nurses from surgical
      departments of two hospitals. The nurses were assigned to two groups based on
      their history of low back pain (with/without). Workplace loading was measured
      continuously for 4 h. RESULTS: No differences in workplace loading between nurses
      with/without a history of low back pain were found. Maximum values of the
      compressive force at the lumbo-sacral junction were high and well above suggested
      workplace load limits. High values occurred only during short-time periods (about
      0.4% of total shift duration). CONCLUSIONS: A system for the assessment of
      overall workplace loading has been developed. First results for nurses suggest
      that critical loadings do exist at the workplace, even so they might not be the
      decisive factor for the development of low back pain. RELEVANCE: Preventative
      measures for low back pain in nursing have to include prevention of critical
      workplace loading. This approach by itself, however, is probably not sufficient.

PMID- 10936427
TI  - Segment inertial properties of Chinese adults determined from magnetic resonance
      imaging.
AB  - OBJECTIVE: To improve the simulation of the task of manual materials handling for
      Chinese laborers, this study estimated the inertial properties of Chinese adults
      by using magnetic resonance imaging. DESIGN: Magnetic resonance imaging was used
      as a means of estimating inertial property. Following the estimation of inertial
      properties for the Chinese subjects, comparison between estimates for Chinese and
      Caucasian populations was made. BACKGROUND: Estimates of segment inertial
      properties are frequently based on data and procedures developed from human
      cadaver studies in which inertial properties have been measured directly. The
      errors might be derived from the utilization of the Caucasian data were
      questioned in our previous study on the spinal force prediction of the Chinese
      subjects during manual lifting. METHODS: Magnetic resonance images were scanned
      at a 20 mm interval from eight males aged 26 (S.D., 4) years. Tissues were
      differentiated and verified using adequate intensity thresholds on each slice,
      and the segmental volume and mass were integrated by slices. The moments of
      inertia for each segment were then determined about the anatomical axes using the
      parallel axis theorem.Results. Results showed that our estimates were close to
      the data derived by Dempster with a slight deviation. Larger percentages of mass
      were found in the upper arm (4.0%) and thigh (13.6%) than in previous studies. On
      the other hand, smaller moments of inertia about three axes were noted in the
      shank. CONCLUSION: Biomechanical modeling of the human body requires accurate
      prediction of body segment parameters that include measures of volume, mass,
      center of mass, and moments of inertia. This study suggests the need to estimate
      the inertial properties of segments from the Chinese population. Application of
      the data may improve the simulation of the task of manual materials handling for
      Chinese laborers in the future studies. RELEVANCE: Biomechanical modeling of the
      human body requires accurate prediction of body segment parameters that include
      measures of volume, mass, center of mass, and moments of inertia. To obtain the
      basic data of segment parameters for the Chinese adults, this study was proceeded
      with the magnetic resonance imaging technique.

PMID- 10936428
TI  - Evaluation of low back muscle surface EMG signals using wavelets.
AB  - OBJECTIVE: To compare the ability of observers to correctly detect the reaction
      time of erector spinae response to unexpected load by inspecting nonprocessed
      electromyographic signals versus inspection of wavelet transformed
      electromyographic signals and versus automatic detection on the same wavelet
      transformed signals. BACKGROUND: Traditionally, electromyographic signal analysis
      is performed using Fourier transform based methods. However, muscle response to
      transients such as unexpected load, have limitations when using these methods of
      electromyographic processing. DESIGN: A comparison was made of the three methods
      using the same signals attained during sudden loading of the trunk. METHODS: 11
      chronic low back pain patients and eleven normal subjects were investigated in
      sudden loading. Surface electromyographic signals were obtained from the erector
      spine muscle at L3. The ability of observers to detect reaction time of erector
      spinae muscle responses of nonprocessed electromyographic signals versus
      inspection of wavelet transformed electromyographic signals versus an automatic
      peak detection program was determined. RESULTS: The results have shown that the
      spine muscle reaction time was easier and more accurately determined in the
      wavelet domain rather than in its original signal representation. CONCLUSION:
      Wavelet transform methods improved the analysis of electromyographic signals in
      the time domain by facilitating the determination of the time of muscle activity.
      RELEVANCE: Wavelet transform could be a valuable tool for electromyographic
      analysis in resolving the psychophysical problem of perception involved in the
      analysis of nonprocessed signals. In clinical environments, where the speed and
      the accuracy of the analysis of electromyographic signal is critical, the wavelet
      based signal processing could be very important.

PMID- 10936429
TI  - The effect of eccentric exercise on intrinsic and reflex stiffness in the human
      hand.
AB  - OBJECTIVE: The purpose of this work was to determine the effect of strenuous
      eccentric exercise on joint stiffness and to separate joint stiffness into
      components due to intrinsic muscle mechanics and delayed reflex muscle
      activation. DESIGN: Subjects performed 100 maximal eccentric contractions, using
      the first dorsal interosseus muscle to abduct the index finger while undergoing a
      20 degrees displacement of the metacarpophalangeal joint. Joint stiffness was
      measured 24 h later during 15% and 65% maximal voluntary contraction and during
      electrical muscle stimulation at 15% of maximal voluntary contraction torque.
      BACKGROUND: Joint stiffness can be varied by changing voluntary muscle activation
      and thereby serves an important role in joint stabilization. Eccentric exercise
      has been shown to result in muscle fiber injury, reducing maximal muscle force.
      However, it is not known whether intrinsic muscle stiffness or reflex stiffness
      is also affected. METHODS: Displacements of 3 degrees amplitude were used to
      estimate joint stiffness about the neutral angle of the index finger. The
      difference between measurements made during voluntary muscle activation and
      electrical muscle stimulation was used to obtain reflex stiffness. RESULTS: There
      was no change in the passive joint stiffness nor was there any change in either
      the intrinsic or reflex stiffness at 15% maximal voluntary contraction. However,
      intrinsic stiffness for the electrically stimulated muscle was higher post
      exercise than pre-exercise, while active joint stiffness at 65% maximal voluntary
      contraction (comprising intrinsic and reflex stiffness) was lower. CONCLUSION:
      The observed mechanical changes are compatible with the hypothesis that type II
      muscle fibers are more susceptible to injury than type I muscle fibers, which
      have higher intrinsic stiffness. RELEVANCE: Muscle stiffness is important for
      maintaining mechanical stability of a joint. The effects of eccentric exercise on
      muscle stiffness are likely analogous to the effects of muscle injury, making
      this a good model for biomechanical changes associated with muscle injury.

PMID- 10936430
TI  - The effect of visual targeting on ground reaction force and temporospatial
      parameters of gait.
AB  - BACKGROUND: Visual targeting has been cited as a confounding factor for gait
      analysis in which measures of ground reaction force and plantar pressure are
      obtained. OBJECTIVE: To investigate the effect of visual targeting on
      temporospatial and kinetic aspects of gait when small targets, such as pressure
      platforms, have to be used. DESIGN: A within subjects repeated measure design was
      used to measure step parameters and ground reaction forces of 11 healthy
      volunteers. METHODS: Subjects were required to walk over a 10 m walkway at a self
      selected pace. A 30x24 cm(2) target area was superimposed over a hidden Kistler
      force plate (60x90 cm(2)) mounted at the midpoint of the walkway. Step parameters
      and ground reaction forces were measured with and without the presence of the
      target. Ground reaction forces were analysed within the time-domain. RESULTS:
      Subjects used visual control strategies when approaching targets of similar
      dimensions to a pressure platform. These strategies were manifested by an
      increase in the variability of the step length onto the target (P<0.05). However,
      targeting was observed to have no affect on the magnitude, timing and variability
      of ground reaction forces when measured within the time-domain and averaged over
      five trials (P>0.05). CONCLUSIONS: Visual control strategies employed while
      walking toward a target area have no affect on ground reaction force parameters
      when measured within the time-domain. RELEVANCE: These findings demonstrate that
      targeting a 30x24 cm(2) target does not affect ground reaction force parameters,
      when a gait protocol that fine-tunes the start position is employed. The findings
      are relevant to gait research in which small force or pressure platforms are used
      to assess gait kinetics.

PMID- 10936431
TI  - Gait and electromyographic analysis of patients recovering after limb-saving
      surgery.
AB  - OBJECTIVE: Control of gait after limb-saving surgery.Design. Case series study.
      BACKGROUND: At the moment little is known about adaptations in patients' gait
      after limb-saving surgery. METHODS: Nineteen patients who underwent limb-saving
      surgery at least 1 yr earlier and 10 normal subjects were studied during
      treadmill walking. The main outcome measures were walking speed, step parameters
      and angular displacement of both legs and EMG of the biceps femoris, rectus
      femoris and medial gastrocnemius in the affected leg. RESULTS: Preferred walking
      speed in the patients was lower than in the controls (0.7 versus 1.1 m/s).
      Furthermore, stance phase of the non-affected leg was lengthened. All patients
      showed reduced stance phase knee flexion in the affected leg, while during the
      swing phase no difference was seen. The EMG signals of the rectus femoris and
      biceps femoris show changes, which are related to the location of surgery.
      CONCLUSIONS: The results showed that the gait pattern of the patients differed
      compared to normal gait. The reduced stance phase knee flexion in the hip group
      is based on a high degree of co-contraction between quadriceps and hamstring
      activity, while in the knee group this is based on the quadriceps avoidance
      pattern. The finding that there is still side-to-side asymmetry indicates that
      there is no complete reorganisation following the massive loss of input and
      output of the leg. It is possible that some reprogramming of the locomotor
      process occur. RELEVANCE: Gait and electromyographic analysis are essential for
      the quantitative assessments of the functional outcome in this type of surgery.

PMID- 10936432
TI  - Investigation into the relationship between the passive flexibility and active
      stiffness of the ankle plantar-flexor muscles.
AB  - OBJECTIVE: The purpose of the study was to investigate the relationship between
      measurements of passive flexibility and active stiffness of the ankle plantar
      flexor muscles. DESIGN: The study was a correlation design. BACKGROUND:
      Flexibility has passive and active components. Little information is available
      regarding the relationship of these measurements in terms of the information that
      they yield on the state of the muscle-tendon unit. METHODS: Free oscillation data
      representing active stiffness was obtained using applied masses equivalent to
      30%, 60% and 90% of the subject's maximal voluntary contraction. The angle of
      dorsiflexion, representing passive flexibility, was measured in standing using
      computer digitisation to obtain the angle.Results. Mean active stiffness values
      were 14280 N/m (30% maximal voluntary contraction), 22260 N/m (60% maximal
      voluntary contraction) and 28010 N/m (90% maximal voluntary contraction).
      Dorsiflexion measurement gave a mean of 34.3 degrees (S.D. 4.8). Correlation's
      obtained for the association between range of motion and active stiffness were
      r=0.01 (30% maximal voluntary contraction), r=0.09 (60% maximal voluntary
      contraction) and r=0.04 (90% maximal voluntary contraction). Moderate reliability
      coefficients of 0.71 (30% maximal voluntary contraction), 0.78 (60% maximal
      voluntary contraction) and 0.68 (90% maximal voluntary contraction) were
      obtained. CONCLUSIONS: The results imply that measurements of passive flexibility
      and active stiffness of the lower leg musculature are independent measures of
      components of muscle-tendon unit flexibility. RELEVANCE: Flexibility is a
      construct with different components of measurement. Etiological studies typically
      relate static flexibility measurements to injury with conflicting outcomes. This
      study suggests that static and active flexibility measures yield different
      information about the muscle tendon unit of the ankle plantar flexors, and that
      researchers should consider this point in the design of etiological studies.

PMID- 10936433
TI  - Analysis of ground reaction forces by means of wavelet transform.
AB  - OBJECTIVE: To identify details of clinical relevance in ground reaction forces by
      means of wavelet transform. DESIGN: A retrospective analysis of gait tests
      performed by total knee replacement patients and a control population has been
      performed. METHODS: The ground reaction forces have been processed by means of
      wavelet transform. Results of the wavelet analysis are represented, in a time
      frequency plane, by tiles. These are coloured in different grey levels associated
      to the values of a suitable energy function of the expansion coefficients,
      resulting from the wavelet transform. RESULTS: The high frequency tiles revealed
      the presence of irregularities with clinical significance in the first part of
      the stance phase. These transients in ground reaction forces are described in a
      quantitative manner allowing to monitor their evolution during the patient
      observation time. The heel strike transient has been identified by the tile
      representation of the vertical component of ground reaction forces and confirmed
      by its correlation with corresponding irregularities in the other components.
      CONCLUSIONS: The tile representation allows to detect and to quantify details not
      easily perceivable by the examiner through traditional techniques. The wavelet
      transform seems particularly appealing for clinical applications such as outcome
      assessment or treatment evaluation and can assist in the definition of normative
      models of ground reaction forces. The effectiveness of the procedure suggest to
      try to automate it. RELEVANCE: The tile representation allows to identify and to
      keep the records of ground reaction forces clinically significant details, such
      as heel strike transient.

PMID- 10936434
TI  - The influence of orthotic devices and vastus medialis strength and timing on
      patellofemoral loads during running.
AB  - OBJECTIVE: To use a musculoskeletal model and simulation of running to examine:
      (1) the influence of two commonly prescribed treatments for patellofemoral pain
      (vastus medialis oblique strengthening and orthoses) and (2) the functional
      significance of timing differences between vastus medialis oblique and vastus
      lateralis on lateral patellofemoral joint loads. DESIGN: A three-dimensional
      musculoskeletal model of the lower extremity was used to simulate running at 4
      m/s. BACKGROUND: Repetitive and excessive joint loading is often associated with
      overuse injuries that require clinical treatments to reduce pain and restore
      function. Affecting one in four runners, patellofemoral pain is one of the most
      common injuries in running. Although conservative treatments have been reported
      to successfully treat patellofemoral pain, the effectiveness is often based on
      subjective or empirical data, which have generated disagreement on the most
      effective treatment. METHODS: Nine subject specific running simulations were
      generated and experiments were performed by applying the treatments and timing
      differences to the nominal simulations. RESULTS: Both treatments significantly
      reduced the average patellofemoral joint load and the vastus medialis
      strengthening also significantly reduced the peak patellofemoral joint load. In
      addition, when the vastus medialis oblique timing was delayed and advanced
      relative to the vastus lateralis timing, a significant increase and decrease in
      the joint load was observed, respectively, during the loading
      response.Conclusions. Increasing vastus medialis oblique strength yielded more
      consistent results across subjects than the orthosis in reducing patellofemoral
      joint loads during running. The effect of orthoses was highly variable and
      sensitive to the individual subject's running mechanics. Vastus medialis oblique
      activation timing is an important determinant of lateral patellofemoral joint
      loading during the impact phase. RELEVANCE: These findings indicate that a
      reduction in patellofemoral pain may be achieved through techniques that
      selectively increase the vastus medialis oblique strength. Therefore, future
      studies should be directed towards identifying such techniques. Additionally, the
      functional significance of timing differences between the vastus medialis oblique
      and vastus lateralis is an important consideration in patellofemoral pain
      treatment and orthoses may be beneficial for some patients depending on their
      running mechanics.

PMID- 10936435
TI  - The manual stress test may not be sufficient to differentiate ankle ligament
      injuries.
AB  - OBJECTIVE: To assess the accuracy of stress tests (anterior drawer, talar tilt)
      in the diagnosis of lateral ligament injuries.Design. Stress tests were performed
      in vitro, and rotation and displacement of the calcaneus relative to the tibia
      were measured. BACKGROUND: Stress tests are commonly used to diagnose ankle
      injuries. However, it is controversial as to whether stress tests can accurately
      differentiate between isolated anterior talofibular ligament injuries and
      combined anterior talofibular and calcaneofibular ligament injuries. METHODS:
      Stress tests were performed in vitro under three conditions with both ligaments
      intact, after sectioning the anterior talofibular ligament, and after sectioning
      the anterior talofibular and calcaneofibular ligament. Motion of the calcaneus
      relative to the tibia was measured in neutral and in 20 degrees of plantarflexion
      at the ankle. RESULTS: There were statistically significant differences among
      cadavers, examiners and positions. There was a difference between isolated
      anterior talofibular ligament sectioning and combined anterior talofibular and
      calcaneofibular ligament sectioning in lateral tilt but not in anterior
      displacement. In contrast, a difference was found between intact and anterior
      talofibular ligament sectioned specimens in anterior displacement but not in
      lateral tilt. However the differences were not great enough to differentiate
      between the two conditions. CONCLUSIONS: Each of the stress tests provides
      reasonable hindfoot displacement but neither is sufficient for accurate diagnosis
      of specific ligament involvement due to the large amount of individual variation.
      RELEVANCE: Many clinicians rely on stress tests to diagnose lateral ligament
      injuries and to assess the extent of anatomic disruption. This in vitro study has
      demonstrated poor correlation between clinical stress tests and the degree of
      ligamentous disruption.

PMID- 10936436
TI  - Early morphometric and anisotropic change in periarticular cancellous bone in a
      model of experimental knee osteoarthritis quantified using microcomputed
      tomography.
AB  - OBJECTIVE: To quantify early stage microstructural changes of periarticular
      cancellous bone in a canine anterior cruciate ligament transection model for
      experimental osteoarthritis. DESIGN: Unilateral transection of the anterior
      cruciate ligament was performed in 10 animals. Bone structure changes were
      quantified in five animals at 3-week post-transection and five animals at 12-week
      post-transection. An additional two non-operated animals were used as controls.
      BACKGROUND: Changes in trabecular architecture of the periarticular cancellous
      bone in early stage post-traumatic osteoarthritis is not well understood.
      Previous studies have found alterations in bone mineral density in experimental
      osteoarthritis suggesting adaptation of the trabecular structure. Early change of
      the periarticular bone following a ligament injury may contribute to the long
      term development of osteoarthritis. METHODS: ++. Bone cores from the medial
      condyles of the femoral and tibial pairs were scanned with a three-dimensional
      microtomographic system. Structural indices were quantified including bone volume
      ratio, bone surface ratio, trabecular thickness, trabecular separation,
      trabecular number, as well as structural anisotropy determined by the mean
      intercept-length method.Results. Significant structural changes were observed at
      3-week post-transection, and were more prominent at 12-week post-transection.
      These changes were accompanied by decreasing anisotropy. CONCLUSIONS:
      Periarticular cancellous bone microstructure is significantly altered in
      experimental osteoarthritis. These changes occurred as early as 3-week post
      transection, and were large at 12-week post-transection. RELEVANCE: The
      pathogenesis of post-traumatic osteoarthritis is poorly understood, but it is
      clear that this disease involves the entire organ system of the joint, including
      the cartilages, synovium, ligaments, and bones. This study focuses on the changes
      that occur in the bones during the early stages following a joint injury, and
      contributes to a better overall understanding of the disease aetiology.

PMID- 10936437
TI  - The remodeling of the primitive human biliary system.
AB  - From 12 weeks of gestation on, a progressive remodeling of the human primitive
      biliary structure or ductal plate occurs. A few parts of the primitive biliary
      structure (peripheral tubular or ductular structures) dilate, migrate toward the
      center of the portal tract, and transform into mature bile ducts, while most of
      them gradually disappear. To the best of our knowledge, quantitative studies have
      been performed only to evaluate the ratio between the number of remodeled bile
      ducts and portal tracts during human fetal development. We studied the remodeling
      of the intrahepatic fetal biliary structures as well as the bile duct to portal
      tract ratio in the developing human liver by immunohistochemistry with monoclonal
      antibodies anti-bile duct type cytokeratins and using a computer-based image
      analysis system. We found that the surface and the perimeter of the portal
      tracts, the longest axis of the migrating peripheral tubular structures, and the
      maturation of bile ducts follow a process continuous and active up to term, but
      they slow between the 20th and the 32nd week of gestation, when intraportal
      granulopoiesis of the liver is active.

PMID- 10936438
TI  - Maturation of human fetal responses to airborne sound in low- and high-risk
      fetuses.
AB  - The purpose of the study was to characterize the onset and maturation of airborne
      sound-elicited responses in low- and high-risk preterm fetuses. In Study 1, a
      total of 91 low-risk fetuses at 27, 30, 33, and 36 weeks GA received three sound
      trials at 90, 100, 105 and 110 dB and three no-stimulus control trials. The onset
      of cardiac acceleration and body movement responses occurred at 30 weeks GA.
      Maturation of the cardiac response was observed with a decrease in threshold from
      105-110 dB at 33 weeks GA to 100-105 dB at 36 weeks GA. In Study 2, the procedure
      was similar except that the 43 high-risk fetuses at 27, 30 and 33 weeks GA did
      not receive sounds at 90 dB. For the high-risk fetuses, the onset of cardiac and
      motor responses also occurred at 30 weeks GA. At 33 weeks GA, those high-risk
      fetuses subsequently born at term showed an increased magnitude of the cardiac
      acceleration response compared to low-risk fetuses. The results indicate that
      both low- and high-risk fetuses begin responding to sounds at the same
      gestational age. Differential responses observed over gestation in the high-risk
      group most likely indicate differential functional development of the auditory
      response system.

PMID- 10936439
TI  - Maternal smoking during pregnancy and infant head circumference at birth.
AB  - Using the Swedish Medical Birth Registry, information on 1,362,169 infants born
      during 1983-1996 was analyzed in order to investigate the relation between
      maternal smoking during pregnancy and infant head circumference at birth. Infants
      of smoking mothers were at an increased risk to have head circumference <32 cm,
      and the adjusted odds ratios (OR) with 95% confidence intervals (CI) for any
      smoking, smoking <10 cigarettes per day, and smoking >/=10 cigarettes per day
      were: 1.65 (1.62-1.68), 1.52 (1.48-1.56), and 1.86 (1.81-1.92), respectively. A
      highly significant association between small head circumference for gestational
      age and maternal smoking was also found (ORs (with 95% CI) were for any smoking,
      <10, and >/=10: 1.58 (1.55-1.61), 1.48 (1.45-1.51), and 1.74 (1.70-1.79),
      respectively). For both outcomes, the observed dose-response effects were highly
      significant (P<10(-6)). Even more alarming was the finding that given a certain
      level of growth retardation, infants of smoking mothers were at an increased risk
      of small head circumference for gestational age compared to infants of non
      smoking mothers (OR (with 95% CI) for any smoking adjusted for 'percentage of
      expected birth weight': 1.08 (1.06-1.10)). Given the evidence that maternal
      smoking specifically affects head growth, until contradictory evidence has been
      found, it seems reasonable to assume that maternal smoking during pregnancy
      affects brain development negatively.

PMID- 10936440
TI  - Association of fetal and maternal carboxyhemoglobin levels in normal and Rh
      alloimmune pregnancies.
AB  - OBJECTIVE: To compare paired antepartum fetal/maternal COHb ratios in whole blood
      from control and alloimmunized pregnancies and to examine the relationships
      between fetal and maternal COHb. METHODS: COHb levels were measured in paired
      fetal and maternal blood samples obtained at cordocentesis in 47 control and 16
      Rh-alloimmunized pregnancies. COHb was determined by gas chromatography. Results
      were analyzed by t-test, regression and analysis of covariance. RESULTS: Although
      fetal/maternal COHb ratios for control and alloimmunized pregnancies were not
      statistically significantly different, i.e. 1. 11+/-0.04 and 1.26+/-0.09,
      respectively (P=0.09), fetal COHb levels were higher in Rh-alloimmunized fetuses
      (P=0.0002). Fetal COHb levels were also higher than paired maternal levels among
      the alloimmunized group (P=0.011), but not among the control group (1. 04+/-0.04,
      P=ns). In univariate regression analysis, fetal and maternal COHb levels were
      significantly correlated with one another in both control (r=0.52, P=0.0002) and
      alloimmunized pregnancy groups (r=0.52, P=0.05). Comparison of the slopes of the
      fetal versus maternal COHb plots for the two groups showed a significant
      difference (P=0.02), with the alloimmunized group having the steeper slope.
      CONCLUSION: Differences in the antepartum fetal-maternal COHb relationships in
      control and alloimmunized groups likely reflect increased endogenous CO
      production among alloimmunized fetuses as a result of pathologic hemolysis.

PMID- 10936441
TI  - Behavioural outcome of school-age children after prenatal exposure to coumarins.
AB  - In utero exposure to coumarin derivatives may affect the development of the
      central nervous system of the child, irrespective of the period of exposure in
      pregnancy. Little is known about effects on development in the long term. The aim
      of the present study was to determine whether prenatal exposure to coumarins
      affects behavioural outcome in children at school age. Behavioural outcome was
      assessed in a cohort of 305 exposed children, aged 7-15 years. Findings were
      compared with those in a cohort of 263 non-exposed controls, matched for sex,
      age, and demographic region. Behaviour was rated by parents and teachers using
      standardized questionnaires: the Groningen Behaviour Checklist Family situation
      (GBF) and the Groningen Behaviour Checklist School situation (GBS), respectively.
      The findings of the GBF were supported by the results of the GBS, filled in by
      teachers who were blind for the exposure status of the child. In comparison to
      the non-exposed children, the coumarin-exposed children scored lower on the
      cluster 'positive task orientation' (GBF P<0.05, GBS P<0.01), they scored higher
      on 'emotional instability' (GBF P<0.001, GBS P<0.05), and they had more problems
      on the social clusters (P<0.01). Based on the results of both questionnaires, we
      conclude that behavioural development may be negatively influenced in school-age
      children after in utero exposure to coumarins, leading to less favourable task
      oriented and social-emotional behaviour. However, the frequency of clinically
      relevant 'problem behaviour' (GBF) was not increased in relation to coumarin
      exposure, the odds ratio was 1.2 (CI(95) 0.7-1.8).

PMID- 10936443
TI  - Introduction. Genetics and the biological functions of integrin adhesion
      receptors

PMID- 10936442
TI  - Stressful delivery influences circulating thrombopoietin (TPO) levels in
      newborns: possible role for cortisol in TPO-mpl binding.
AB  - The regulation mechanism of circulating thrombopoietin (TPO) level in human
      newborns remains unknown. In the present study, we examined whether the TPO
      concentrations in cord blood were influenced by the difference in the delivery
      method and the presence or absence of maternal/fetal complications. Cortisol
      levels were simultaneously measured to assess the adrenal response of fetuses.
      Both the TPO level and the cortisol level were substantially greater in the
      neonates delivered vaginally with and without the complications than in those
      delivered by cesarean section without the complications. The binding assay showed
      that the incubation of mpl(+)/BaF3 cells with cortisol gave rise to a significant
      decrease in the binding sites of TPO. These results suggest that the stress to
      the fetuses near the time of delivery affects the cord blood TPO levels, which
      may be mediated in part by the action of cortisol on the TPO-mpl binding system.

PMID- 10936444
TI  - Cell-cell adhesion via the ECM: integrin genetics in fly and worm.
AB  - Integrins are essential for the development of the two genetically tractable
      invertebrate model organisms, the nematode worm Caenorhabditis elegans and the
      fruit fly Drosophila melanogaster. Just two integrins are present in C. elegans:
      one putative RGD binding integrin alphapat-2betapat-3, corresponding to
      Drosophila alphaPS2betaPS and vertebrate alpha5beta1, alphaVbeta1 and
      alpha8beta1, and one putative laminin binding integrin alphaina-1betapat-3,
      corresponding to Drosophila alphaPS1betaPS and vertebrate alpha3beta1,
      alpha6beta1 and alpha7beta1. In this review, the function of this minimal set of
      integrins during the development of these two invertebrates is compared. Despite
      the differences in bodyplan and developmental strategy, integrin adhesion to the
      extracellular matrix is required for similar processes: the formation of the link
      that translates muscle contraction into movement of the exoskeleton, cell
      migration, and morphogenetic interactions between epithelia. Other integrin
      functions, such as regulation of gene expression, have not yet been
      experimentally demonstrated in both organisms. Additional proteins have been
      characterised in each organism that are essential for integrin function,
      including extracellular matrix ligands and intracellular interacting proteins,
      but so far different proteins have been found in the two organisms. This in part
      represents the fact that the characterisation of the full set of interacting
      proteins is not complete in either system. However, in other cases different
      proteins appear to be used for similar functions in the two animals. The
      continued use of genetic approaches to identify proteins required for integrin
      function in these two model organisms should lead to the identification of the
      minimal set of conserved components that form integrin adhesive structures.

PMID- 10936445
TI  - In vivo functions of integrins: lessons from null mutations in mice.
AB  - The integrin family (Hynes, R.O., 1992. Integrins: versatility, modulation, and
      signaling in cell adhesion. Cell 69, 11-25) is composed of at least 24
      heterodimers formed from eight beta subunits and 18 alpha subunits. Thus far,
      mice expressing null mutations of seven of the eight beta subunits and 13 of the
      18 known alpha subunits have been generated, With only a few exceptions, the
      phenotypes of each of the knockout lines are quite distinct. Studies utilizing
      integrin knockout mice and cells derived from these mice have provided
      considerable and sometimes surprising insights into unique functions of
      individual members of this family.

PMID- 10936446
TI  - Genetic analysis of integrin function in man: LAD-1 and other syndromes.
AB  - The integrins are cell membrane receptors composed of alpha and beta subunits
      which orchestrate adhesive events in all tissues of the body (Hynes, R.O., 1992.
      Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69, 11
      25; and Hynes, R.O., 1999. Cell adhesion: old and new questions. Trends Cell
      Biol. 9, M33-37). At present 18 alpha subunits and 8 beta subunits have been
      identified which are loosely organised into families. There are three inherited
      autosomal recessive diseases in man which involve germline mutations in genes
      coding for integrins. Leukocyte adhesion deficiency-1 (LAD-1) is the result of
      mutations in the beta2 subunit of the CD11/CD18 integrins, LFA-1, Mac-1, p150,95
      and alphadbeta2. The bleeding disorder Glanzmann thrombasthenia is caused by
      mutations in either the alpha or beta subunit of the platelet integrin,
      alphaIIbbeta3. Thirdly, it is now recognised than one of the variants of the
      usually lethal skin blistering disorder, epidermolysis bullosa (JEB-PA), is
      caused by mutation in either the alpha or beta subunit of the epithelial
      hemidesmosome integrin, alpha6beta4. Many of the mutations cause defective
      alphabeta heterodimer formation. The majority of the beta subunit mutations are
      in the conserved N-terminal region known as the betaI domain. It is suggested
      that this region participates in alphabeta heterodimer formation.

PMID- 10936447
TI  - A disease-associated glycine substitution in BP180 (type XVII collagen) leads to
      a local destabilization of the major collagen triple helix.
AB  - BP180 is a homotrimeric transmembrane protein with a carboxy-terminal ectodomain
      that forms an interrupted collagen triple helix. Null type mutations in the BP180
      gene produce a recessive subepidermal blistering disease, non-Herlitz junctional
      epidermolysis bullosa. Like the null mutations, a glycine substitution (G627V)
      within the longest BP180 collagenous domain (COL15) is also associated with the
      recessive skin disease; however, unlike the null mutations, this glycine
      substitution appears to act in a dominant fashion to give rise to a novel form of
      random pitting dental enamel hypoplasia. The dominant effects of this mutation
      were thought to be due to alterations in the assembly and/or stability of this
      BP180 collagenous region. To further investigate this issue, a structural
      analysis was performed on recombinant forms of the wild type and G627V mutant
      BP180 ectodomain. Both proteins were found to form collagen-like triple helices
      with very similar Stokes radii and melting temperatures and exhibited very
      similar rates of synthesis, secretion and turn-over. Tryptic digestion analysis
      revealed that the mutant G627V-sec180e contains an additional highly sensitive
      proteolytic site that maps within the region of the mutation. Thus, the disease
      associated G627V mutation in BP180 does not grossly alter protein structure, but
      causes a local destabilization of the triple-helix that exposes sensitive
      residues to the in vitro effects of trypsin and possibly affects its structure
      function in vivo.

PMID- 10936448
TI  - Cooperative equilibrium transitions coupled with a slow annealing step explain
      the sharpness and hysteresis of collagen folding.
AB  - Heat and guanidinium-induced denaturation curves of collagen III and its
      fragments were fitted by theoretical models to explain the extreme sharpness and
      the hysteresis between unfolding and refolding. It was shown that a recently
      proposed kinetic model for collagen denaturation does not account for the
      observed steepness, with physically reasonable values of activation energy and
      frequency factors in the Arrhenius equation. The extreme slope, which amounts to
      0.38 per centigrade for collagen III at the midpoint of its transition, can only
      be explained by a highly cooperative equilibrium model. The refolding curve is
      shifted to lower temperatures by 6 degrees C for collagen III and reversible
      unfolding matching the initial profile of the native protein is observed only
      after long-time annealing. A simple formalism is proposed by which experimental
      denaturation and refolding curves are quantitatively described. The transition
      proceeds via many cooperative steps with slightly different equilibrium constants
      for unfolding and refolding. Hysteresis and annealing are caused by very slow
      steps, which are probably connected with a rearrangement of misfolded regions.
      These slow steps disappear with decreasing size of collagen fragments and
      hysteresis is not found for collagen model peptides.

PMID- 10936449
TI  - Osteopontin is expressed by adult human osteoarthritic chondrocytes: protein and
      mRNA analysis of normal and osteoarthritic cartilage.
AB  - Osteopontin, a sulfated phosphoprotein with cell binding and matrix binding
      properties, is expressed in a variety of tissues. In the embryonic growth plate,
      osteopontin expression was found in bone-forming cells and in hypertrophic
      chondrocytes. In this study, the expression of osteopontin was analyzed in normal
      and osteoarthritic human knee cartilage. Immunohistochemistry, using a monoclonal
      anti-osteopontin antibody was negative on normal cartilage. These results were
      confirmed in Western blot experiments, using partially purified extracts of
      normal knee cartilage. No osteopontin gene expression was observed in
      chondrocytes of adult healthy cartilage, however, in the subchondral bone plate,
      expression of osteopontin mRNA was detected in the osteoblasts. In cartilage from
      patients with osteoarthritis, osteopontin could be detected by
      immunohistochemistry, Western blot analysis, in situ hybridization, and Northern
      blot analysis. A qualitative analysis indicated that osteopontin protein
      deposition and mRNA expression increase with the severity of the osteoarthritic
      lesions and the disintegration of the cartilaginous matrix. Osteopontin
      expression in the cartilage was limited to the chondrocytes of the upper deep
      zone, showing cellular and territorial deposition. The strongest osteopontin
      detection was found in deep zone chondrocytes and in clusters of proliferating
      chondrocytes from samples with severe osteoarthritic lesions. These data show the
      expression of osteopontin in adult human osteoarthritic chondrocytes, suggesting
      that chondrocyte differentiation and the expression of differentiation markers in
      osteoarthritic cartilage resembles that of epiphyseal growth plate chondrocytes.

PMID- 10936450
TI  - Bovine joint capsule and fibroblasts derived from joint capsule express
      aggrecanase activity.
AB  - Bovine joint capsule was maintained in explant culture in the presence of bovine
      aggrecan monomer and it was shown that the aggrecan monomer was degraded. Amino
      terminal sequence analysis of the resulting aggrecan core protein fragments
      revealed that the core protein was cleaved at five specific sites attributed to
      glutamyl endopeptidases referred to as aggrecanase activity. Fibroblast cultures
      were established from explant cultures of joint capsule and when these cells were
      exposed to aggrecan, cleavage of the core protein of aggrecan at the aggrecanase
      sites was observed. Inclusion of either retinoic acid or interleukin-1alpha in
      medium of either joint capsule explant cultures or fibroblast cultures did not
      increase the rate of cleavage of exogenous aggrecan present in the culture
      medium. When aggrecan monomer was incubated with conditioned medium from explant
      cultures of joint capsule maintained in medium, degradation could be detected
      after 10 min. After a 6-h incubation period the same fragments of aggrecan core
      protein were observed as those for tissue or cells incubated directly with
      aggrecan monomer. RT-PCR analysis of mRNA extracted from joint capsule
      fibroblasts showed that these cells express both aggrecanase-1 and -2 [ADAMTS-2
      (Tang) and ADAMTS-5].

PMID- 10936451
TI  - A versatile assay for gelatinases using succinylated gelatin.
AB  - A spectrophotometric assay using succinylated gelatin as substrate is described
      for measuring the catalytic activity of gelatinases. The assay is based on
      measurement of primary amines exposed as a result of hydrolysis of the substrate
      by gelatinases. Comparison of hydrolysis by matrix metalloproteinase (MMP) 1, 2,
      3, 7, 9 indicated that succinylated gelatin was primarily digested by MMP-2 and 
      9. The assay is rapid (<60 min), specific, suitable for measuring gelatinolytic
      activity of enzymes and high volume screening of MMP-2 and -9 inhibitors.
      Sensitivity of the assay is comparable to that of gelatin zymography, under
      similar experimental conditions. Thus, the assay combines ease and rapidity of
      assays based on synthetic peptide substrates with specificity of the gelatin
      zymography technique.

PMID- 10936452
TI  - Tracing the evolution of vertebrate fibrillar collagens from an ancestral alpha
      chain.
AB  - From considerations of gene structure, phylogenetic analysis, modular
      organisation of related proteins and fibril shapes, we suggest a model for the
      evolution of contemporary vertebrate fibrillar collagens from a common ancestral
      alpha chain.

PMID- 10936453
TI  - Deplasticizing or etching of epoxy sections with different concentrations of
      sodium ethoxide to enhance the immunogold labeling.
AB  - The study's purpose was to obtain improved "deplasticizing" of epoxy sections for
      immunoelectron microscopy. Epoxy-embedded renal swine tissue with immune complex
      deposits was used. Ultrathin sections were mounted on uncoated grids or on carbon
      stabilized formvar grids. The sections were exposed to different concentrations
      of sodium ethoxide, and they were subjected to immunogold labeling with anti-IgG.
      Etching with > or =8% of saturated solution gave completely deplasticized
      sections. Sections etched with 2-4% solution were only partly deplasticized, but
      these sections were detached if mounted on uncoated grids, and the yields of
      immunolabeling were significantly decreased compared with the deplasticized ones.
      Sections exposed to < or =1% solution were not detached from the uncoated grids.
      Double-sided labeling of uncoated sections etched with 1% solution yielded
      approximately the same immunolabeling as for the completely deplasticized formvar
      supported sections, and they gave better ultrastructural preservation of the
      tissue. We have established that etching epoxy sections on non-supported grids
      with a diluted solution of sodium ethoxide may be preferable for immunoelectron
      microscopy.

PMID- 10936455
TI  - Phase identification of microfeatures using EPMA methods, especially high
      resolution X-ray spectroscopy
AB  - Methods of electron-probe microanalysis (EPMA), with some input from scanning and
      transmission electron microscopy (SEM/TEM), are applied for the identification of
      micro-scale constituents in a solid matrix. The subject of the study is a
      magnesium alloy composite, which contains silicon carbide-based fibres made by a
      liquid metal infiltration process. Backscattered electron imaging of the
      composite in the SEM showed that during composite manufacture, fibres were
      chemically attacked by the metal, many of the fibres exhibiting three distinct
      grey levels, indicative of different reaction zones, and others appearing
      uniformly black. EPMA measurements showed that each region contained
      approximately 12wt.% oxygen and that penetration of the fibre by magnesium was
      accompanied by a reduction in the concentration of silicon and carbon. From
      studying the position and shape of specific X-ray lines it was shown that
      magnesium penetration involved a chemical reaction with silicon oxycarbide,
      established in earlier EPMA studies as one of the fibre constituents. Also, in
      the outermost region, aluminium in the alloy reacted with free carbon in the
      fibre to form aluminium carbide and with magnesium to produce a Mg-Al
      intermetallic. The composition of black fibres was quite different from the grey
      ones, with negligible silicon and only a small amount of aluminium. Oxygen levels
      in black fibres were consistent with complete oxidation, indicating these fibres
      were subjected, locally, to severe oxidising conditions during composite
      manufacture. In the metal matrix itself, particles of a mixed magnesium/aluminium
      oxide, silicon carbide and magnesium silicide were observed, the latter two
      phases forming as silicon and carbon were ejected from fibres.

PMID- 10936454
TI  - Spatial distribution of perylenequinones in lichens and extended quinones in
      quincyte using confocal fluorescence microscopy.
AB  - The application of confocal fluorescence microscopy and microspectrofluorimetry
      to the characterization of the distribution of organic compounds in bulk lichens
      and mineral structures is demonstrated. Perylenequinones and extended quinones
      were chosen as both model compounds and as the naturally occurring fluorophores.
      These molecules occur, respectively, in corticolous microlichens and in a pink
      colored mineral called quincyte. The structures of quincyte and of the lichens
      Cryptothelium rhodotitton and Graphis hematites are described, and the
      possibilities of energy dissipation and photoprotection mechanisms in these
      lichens are discussed. This study also illustrates how, for a wide range of
      specimens, naturally occurring quinone fluorophores in the specimen can be
      exploited directly to yield chemical and structural information without using
      fluorescent labelling. These intrinsic quinonoid compounds have molecular
      fluorescence yields and laser damage thresholds comparable or superior to common
      microscopy dyes, and can therefore be used to obtain high-contrast 3D
      fluorescence imaging without the complications introduced by dye labelling.

PMID- 10936456
TI  - Ergastoplasmic paracrystalline inclusion bodies in the adipose gonadal envelope
      and fat body of the glow worm, Lampyris noctiluca (Insecta, Coleoptera).
AB  - The gonads of glow worm larvae are enveloped by adipose tissue which represents a
      specialized fat body. The adipose gonadal envelope, and also to a lesser extent
      the fat body cells, contain tubular paracrystalline inclusion bodies (PIBs).
      Cells of other tissues are devoid of such inclusions. The PIBs form in the
      cisternae of rough ER. In young larvae PIB formation is sparse, but at advanced
      larval stages PIBs often occur as bundles in stacks of ergastoplasm. Typically, a
      PIB within a cisterna consists of four to seven parallel tubules. The outer
      diameter of a tubule is ca 28.8 nm and the width of the tubule lumen ca 12.2 nm.
      The "wall" of a tubule contains globular protein subunits of ca 8.3 nm diameter;
      the subunits are arranged helically. Since the adipose gonadal envelope
      progresses through a cytological differentiation process during differentiation
      and maturation of the gonads, the increased number of PIBs may indicate enhanced
      metabolic activity of the tissue related to nutrition of the growing gonads.

PMID- 10936457
TI  - Energy loss near edge structure of sulfur in non-stoichiometric CuInS(2)
AB  - Non-stoichiometric CuInS(2) is a novel material for thin film solar cells.
      Electron energy loss spectrometry analysis shows that there are considerable
      lateral inhomogeneities on a scale of less than 100nm. It is as yet unknown
      whether the Cu or In surplus comes in nanoprecipitates irregularly distributed in
      the otherwise stoichiometric matrix, or forms supercells where particular atoms
      are replaced by their complements. This question bears important consequences for
      the understanding of the local electronic structure and the mechanism of
      undesired recombination processes in the cell. Since the energy-loss near edge
      structure of ionisation edges (ELNES) mirrors the local density of unoccupied
      states it should be different in the two cases. We compare the sulfur L(2,3)
      ELNES of a Cu-rich and of an In-rich specimen with simulations of supercells
      based on the TELNES/WIEN97 code. Faint differences in the edge shape can be made
      visible using difference spectra. They agree reasonably well with simulations.
      The results show that the surplus species exists as a separate non-stoichiometric
      phase and not merely as a precipitate of elemental Cu or In.

PMID- 10936458
TI  - A comparative study of the immunogold labeling on H(2)O(2)-treated and heated
      epoxy sections.
AB  - The purpose of this study was to compare the intensity of the immunogold labeling
      of H(2)O(2)-treated and heated epoxy sections. Renal swine tissue with glomerular
      immune complex deposits with reactivity against IgG was embedded in epoxy resin.
      Immunogold labeling with anti-IgG was performed on sections from these blocks.
      Some of these sections were treated by H(2)O(2), others were heated in a citrate
      solution, while some were not treated at all. Some epoxy sections, which had been
      exposed to both H(2)O(2) and heat, were also exposed to the same immunolabeling.
      The heated epoxy sections obtained an yield of specific immunogold labeling,
      which was twice as large as the labeling of the H(2)O(2)-treated sections. The
      yield of immunolabeling of the sections that had been exposed to both H(2)O(2)
      and heat was not significantly different from the sections that were only exposed
      to heat. The non-treated sections were very weakly labeled with anti-IgG. We
      believe that both H(2)O(2) and heat have the ability to break some chemical bonds
      between the epoxy resin and the antigens, but heating in citrate buffer has a
      larger potential in this respect than H(2)O(2). We interpret the results from the
      combined treatment with H(2)O(2) and heat in the following way; the bonds that
      are broken by H(2)O(2) will also be broken by heating in citrate solution. The
      practical significance of these results is that heating in citrate buffer is a
      more convenient method for enhancing the immunolabeling of epoxy sections than
      treatment with H(2)O(2).

PMID- 10936459
TI  - Application of atomic force microscopy to microbial surfaces: from reconstituted
      cell surface layers to living cells.
AB  - The application of atomic force microscopy (AFM) to probe the ultrastructure and
      physical properties of microbial cell surfaces is reviewed. The unique
      capabilities of AFM can be summarized as follows: imaging surface topography with
      (sub)nanometer lateral resolution; examining biological specimens under
      physiological conditions; measuring local properties and interaction forces. AFM
      is being used increasingly for: (i) visualizing the surface ultrastructure of
      microbial cell surface layers, including bacterial S-layers, purple membranes,
      porin OmpF crystals and fungal rodlet layers; (ii) monitoring conformational
      changes of individual membrane proteins; (iii) examining the morphology of
      bacterial biofilms, (iv) revealing the nanoscale structure of living microbial
      cells, including fungi, yeasts and bacteria, (v) mapping interaction forces at
      microbial surfaces, such as van der Waals and electrostatic forces, solvation
      forces, and steric/bridging forces; and (vi) probing the local mechanical
      properties of cell surface layers and of single cells.

PMID- 10936460
TI  - An introduction to off-axis electron holography
AB  - The technique of off-axis electron holography is introduced and reviewed. The
      history of the topic is discussed briefly looking at the origin of electron
      holography and the reasons for its growth in recent years around the world. The
      formation and numerical reconstruction of the hologram is discussed in detail on
      a theoretical and practical level. The spread of holography is illustrated
      through a number of applications ranging from ultra high resolution studies of
      crystal structures, the imaging of magnetic and electric fields, the
      determination of sample composition and morphology and the use of holography for
      imaging biological specimens.

PMID- 10936461
TI  - Fibrillin-rich microfibrils of the extracellular matrix: ultrastructure and
      assembly.
AB  - Fibrillin-rich microfibrils are a unique class of extensible connective tissue
      macromolecules. Their critical contribution to the establishment and maintenance
      of diverse extracellular matrices was underlined by the linkage of their
      principal structural component fibrillin to Marfan syndrome, a heritable
      connective tissue disorder with pleiotropic manifestations. Microscopy and
      preparative techniques have contributed substantially to the understanding of
      microfibril structure and function. The supramolecular organisation of
      microfibrillar assemblies in tissues has been examined by tissue sectioning and X
      ray diffraction methods. Published findings are discussed and new information
      reported on the organisation of microfibrils in the ciliary zonular fibrils by
      environmental scanning electron microscopy. This review summarises microscopy and
      X-ray diffraction studies that are informing current understanding of the
      ultrastructure of fibrillin-rich microfibrils.

PMID- 10936462
TI  - Liposomes as protective agents of stratum corneum against octyl glucoside: a
      study based on high-resolution, low-temperature scanning electron microscopy.
AB  - The ability of phosphatidylcholine (PC) liposomes to protect pig stratum corneum
      (SC) against the action of the nonionic surfactant octyl glucoside (OG) was
      investigated "in vitro" using double-layer coating for high-resolution, low
      temperature scanning electron microscopy. This technique has been useful in
      preventing drying artifacts in the study of biological materials. The treatment
      of SC with OG led to a perturbation mainly in the corneocytes. However, the
      incubation of the tissue with liposomes prior to the OG treatment resulted in a
      progressive decrease in these perturbations and, consequently, in the progressive
      protection of the SC against the action of the surfactant.

PMID- 10936463
TI  - An immunofluorescence technique for staining ciliated protozoans: highlighting
      cytoplasmic microtubular arrays and stages of micronuclear meiosis.
AB  - Ciliated protozoans represent useful organisms for studying the processes
      involved in the induction and progression of meiosis. In this short report we
      describe a technique that has allowed us to examine different meiosis phases
      during the sexual reproduction of Blepharisma japonicum. In order to visualize
      the phases of meiosis, sexually reproducing pairs were stained by an enhanced
      technique of anti-tubuline indirect immunofluorescence. Meiotic micronuclei,
      particularly those showing metaphase spindles, were clearly highlighted. The
      technique also heavily decorates the main microtubular cytoplasmic arrays in
      Blepharisma.

PMID- 10936464
TI  - Cracking of titanium alloys under cathodic applied potential
AB  - The slow-strain-rate test technique was used to evaluate the susceptibility of Ti
      Gr-7 and Ti Gr-12 to hydrogen-induced-cracking and/or stress corrosion cracking.
      Ti Gr-7 and Ti Gr-12 are two candidate container materials for the multi-barrier
      package for nuclear waste. The tests were done in a deaerated 90 degrees C acidic
      brine (pH approximately 2.7) containing 5 weight percent (wt. %) NaCl using a
      strain rate of 3.3x10(-6)s(-1). Before being tested in the acidic brine,
      specimens of each alloy were pulled inside the test chamber in the dry condition
      at ambient temperature. Then, while in the test solution, specimens were strained
      under different cathodic controlled potentials. These controlled potentials were
      selected based on the corrosion potential measured in the test solution before
      the specimens were strained. Results indicate that the times to failure (TTF) for
      Ti Gr-12 were much shorter than those for Ti Gr-7. Furthermore, as the applied
      potential became more cathodic, Ti Gr-12 showed reduced ductility in terms of
      percent reduction in area and true fracture stress (sigma(f)). In addition, the
      TTF and percent elongation reached the minimum values when Ti Gr-12 was tested
      under an impressed potential of -1162mV. However, for Ti Gr-7, all these
      ductility parameters were not significantly influenced by the changes in applied
      potential. In general, the results of hydrogen analysis by secondary ion mass
      spectrometry showed increased hydrogen concentration at more cathodic controlled
      potentials. Optical microscopy and scanning electron microscopy were used to
      evaluate the morphology of cracking both at the primary fracture face and the
      secondary cracks along the gage section of the broken tensile specimen.
      Transgranular secondary cracks were observed in both alloys possibly resulting
      from the formation of brittle titanium hydrides due to cathodic charging. The
      primary fracture face was characterized by dimpled microstructure indicating
      ductile failure.

PMID- 10936465
TI  - Oxaliplatin clinical activity: a review.
AB  - Oxaliplatin (Eloxatin), a recently developed third-generation cisplatin analogue
      with a 1,2-diaminocyclohexane (DACH) carrier ligand, has displayed preclinical
      and clinical activity in a wide variety of tumour types. Synergistic with 5-FU in
      colorectal cancer (CRC), the combination has proven efficacy in 5-FU-resistant
      advanced disease and in previously untreated CRC, as demonstrated in controlled
      phase III trials, while evaluation in the adjuvant setting is ongoing. Due to its
      excellent safety profile, its unique mechanism of action and lack of cross
      resistance with other active agents in CRC, oxaliplatin has also been combined
      with CPT-11 and Raltitrexed with promising results. Trials in pretreated and
      untreated advanced ovarian cancer (AOC), as a single agent or in combination with
      cisplatin, cyclophosphamide or paclitaxel, indicate a yet to be defined role in
      AOC and confirm its lack of cross-resistance with cis/carboplatin. Clinical
      investigations of single agent and combination therapies in breast, lung,
      prostate and germ-cell carcinomas, non-Hodgkin's lymphoma and malignant
      mesothelioma are being pursued. While the role of oxaliplatin in medical oncology
      is yet to be fully defined, it appears to be an important new anticancer agent.

PMID- 10936466
TI  - Treatment of patients with high-grade non-Hodgkin's lymphoma aged over 70 years
      with an all-oral regimen combining idarubicin, etoposide and alkylators.
AB  - In elderly patients age-specific comorbidity often reduces the possibility of
      administering intensive chemotherapy and of obtaining response to treatment.
      Therefore, chemotherapy must differ from that for non-elderly patients, while
      maintaining the primary goal of a complete clinical response. We treated 19
      patients over the age of 70 years (median age 75 years, range 70-86) with stage
      II-IV high-grade non-Hodgkin's lymphoma (NHL) with a combination regimen
      including idarubicin plus etoposide and prednimustine (or
      chlorambucil+prednisone), all administered orally on an outpatient basis. The
      therapeutic schedule included six 5-day courses of idarubicin 20 mg/sqm on day 1
      (or 10 mg/sqm on days 1 and 3 in the nine patients last treated), etoposide 60
      mg/sqm/12 h days 2-5, prednimustine 60 mg/sqm days 2-5, G-CSF 300 microg/day from
      day+7 until PMN>1000/microl. In ten patients prednimustine was replaced by
      chlorambucil 10 mg/sqm, days 2-5, and prednisone 50 mg days 2-5, because of non
      availability of the drug. Of the 19 patients submitted to this regimen 15 (79%)
      obtained a clinical response: eight reached a complete response (CR), and seven a
      partial response (PR). Hematologic toxicity was generally mild. Only three
      patients had to be hospitalised for infection. Except alopecia, non-hematologic
      toxicities were negligible. At a median follow-up of 16 months, five of eight
      patients who obtained CR relapsed (median CR duration 7 months). The actuarial
      median survival is 34 months (range 6-46). This study demonstrates the
      feasibility and efficacy of an all-oral regimen including idarubicin, plus
      etoposide and prednimustine (or chlorambucil+prednisone) in NHL patients aged
      over 70 years.

PMID- 10936467
TI  - Capecitabine, a new oral fluoropyrimidine for the treatment of colorectal cancer.
AB  - Capecitabine (Xeloda)(R) was developed as a tumour-selective fluoropyrimidine
      carbamate to achieve higher intratumoural 5-FU level and lower toxicity than 5
      FU. Capecitabine passes unchanged through the gastrointestinal tract and is
      metabolised in the liver to 5'-deoxy-5-fluorocytidine (5'-DFCR). Here it is
      converted to doxifluridine (5'-DFUR) and finally, 5'-DFUR is metabolised by
      thymidine phosphorilase to 5-FU at the tumour site. Preclinical studies have
      demonstrated capecitabine's activity in both 5-FU-sensitive and 5-FU-resistant
      tumours. In a randomised phase II trial in advanced colorectal cancer the
      recommended dose and schedule of Capecitabine is 2.510 mg/m(2)/day (total dose
      divided into two equal morning and evening doses) given in an intermittent
      schedule (2 weeks on/1 week off). Phase III trials in patients with advanced
      colorectal cancer show a better response rate than the Mayo Clinic schedule, with
      no differences in terms of DR, PFS. Diarrhoea and hand-foot syndrome were the
      principal grade 3/4 toxicities noted, occurring in 10% and 16% of patients,
      respectively. The selectivity of this drug opens an important prospective in the
      treatment of colorectal cancer in advanced and adjuvant setting.

PMID- 10936468
TI  - Current status of the development of trans-platinum antitumor drugs.
AB  - The discovery in the 1990s of several trans-Pt complexes with in vitro and in
      vivo activity against tumor cells sensitive and/or resistant to cisplatin has
      forced the re-evaluation of the structure-activity relationships for platinum
      antitumor drugs. Because the determinant factors of cytotoxic activity of trans
      platinum complexes do not follow the same patterns as those found for cisplatin
      and its analogues, the differences in cellular and biochemical pharmacology
      between trans-platinum antitumor complexes and cisplatin might be systematically
      exploited to design novel trans-platinum complexes with a clinical profile
      complementary to that of cisplatin and related analogues. Therefore, there may
      exist a novel molecular rationale for new platinum antitumor drugs development in
      the twenty-first century.

PMID- 10936469
TI  - Hormone therapy of prostate cancer: is there a role for antiandrogen monotherapy?
AB  - Androgen suppressive maneuvers still represent the gold standard for prostate
      cancer patients. However, they are associated with side effects (fatigue, sexual
      impotence, hot flushes, anemia, anxiety, depression and osteoporosis) all of
      which have a negative impact on quality of life. Nonsteroidal antiandrogens
      compete with dihydrotestosterone for the linkage of its own receptors. These
      compounds are commonly used in combination with suppressive maneuvers. However,
      there is a growing experience with them as monotherapy, based on the possibility
      to spare gonadal function and therefore prevent the effects related to its
      suppression. Many studies have demonstrated the feasibility and safety of this
      approach, which can represent a valuable alternative to suppressive maneuvers for
      patients wishing to retain sexual function, especially for those without distant
      metastases. Unfortunately, none of the comparative studies performed so far had
      the power to detect the equivalence between monotherapy and castration.

PMID- 10936470
TI  - Prostate cancer incidence and mortality trends among elderly and adult Europeans.
AB  - Prostate cancer is a common malignancy primarily of elderly men, with incidence
      rates rapidly increasing, owing to the population ageing and the introduction of
      more sensitive diagnostic procedures. Although the effectiveness of a screening
      test remains controversial, the decreasing mortality rates, which recently
      emerged in the USA, may be partly attributable to the changes of patterns of
      care, thus suggesting a potential effect of preventive measure. The object of
      this study is to examine time trends in incidence and mortality from prostate
      cancer in European Union (EU) countries, with particular attention to possible
      differences between the elderly (65 years old or over) and younger or middle age
      adults (35-64 years old). EUROCIM, the data base created by the European Network
      of Cancer Registries, provided the incidence and mortality data for the 12 EU
      Countries analysed (namely: Finland, Denmark, Scotland, England and Wales,
      Ireland and The Netherlands in Northern Europe; Austria, Germany and France in
      Central Europe; Italy, Spain and Portugal in Southern Europe), for the 1978-1994
      period. Incidence and mortality time trends, expressed as mean difference per
      cent (MD%) per year, were estimated by a Poisson log-linear regression model.
      Higher resolution analyses were also carried out to check differences in time
      trends by age class within the two groups under study. Upward mortality trends
      occurred in several countries, excepting Ireland, Austria and Southern Europe,
      but only for younger and middle aged adults. Rates increased more rapidly in
      older age groups; a clear north-south gradient appeared both in the elderly and
      in younger adults; for the elderly, MD% higher than +1.5 for most countries of
      Northern Europe, MD% around +1 for Central Europe, and MD% less than +1 for
      Southern Europe were registered, with lower values for younger people. Incidence
      rates rose across the period considered, almost in all countries both for elderly
      and for younger and middle age adults, increasing more rapidly in younger age.
      Incidence trends showed a less clear geographic pattern than for mortality. In
      the younger group, high MD%, ranging in Northern Europe from +3.2 in Finland and
      England and Wales to +5.7 in The Netherlands, were observed, while in the South
      values ranged between +4.2 and +5.0. In Central Europe, very high MD%, ranging
      between +8.4 in France and +16.6 in Austria, were noted. No significant trends
      were observed for Denmark, Ireland and Portugal. For the elderly the increase was
      generally lower and no significant trend was observed in Germany and Portugal.
      Interaction between age and calendar period in the older group was observed for
      most of the considered countries. With reference to mortality, the MD% showed a
      tendency to rise, with increasing age, while no consistent pattern emerged for
      incidence. The observed incidence trends are probably a consequence of the
      different times in which the more recent detection methods were introduced in
      each country, and of the different policies adopted by each health care system
      towards the elderly. A comparison with the USA data suggests that in the next
      future a favourable downward mortality trend could be expected also in some EU
      Countries and, particularly, for younger age groups, even though prostatic cancer
      in old patients will remain a great burden, which National Health Care Systems
      will have to face in the next decades.

PMID- 10936471
TI  - Proteinuria as a risk factor for cardiovascular disease and mortality in older
      people: a prospective study.
AB  - BACKGROUND: The prognostic significance of proteinuria in older people is not
      well defined. We examined the associations between proteinuria and incident
      coronary heart disease, cardiovascular mortality, and all-cause mortality in
      older people. SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in
      1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7
      years) attending the 15th biennial examination of the Framingham Heart Study.
      Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%),
      and greater-than-trace (4.5%). Cox proportional hazards analyses were used to
      determine the relations of baseline proteinuria to the specified outcomes,
      adjusting for other risk factors, including serum creatinine level. RESULTS:
      During 17 years of follow-up, there were 455 coronary heart disease events, 412
      cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was
      associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence
      interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for
      greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria
      was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4),
      and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7). CONCLUSION: Proteinuria is
      a significant, although relatively weak, risk factor for all-cause mortality in
      men and women, and for cardiovascular disease mortality in women.

PMID- 10936472
TI  - Treatment of low back pain exacerbations with willow bark extract: a randomized
      double-blind study.
AB  - PURPOSE: Herbal medicines are widely used for the treatment of pain, although
      there is not much information on their effectiveness. This study was designed to
      evaluate the effectiveness of willow (Salix) bark extract, which is widely used
      in Europe, for the treatment of low back pain. SUBJECTS AND METHODS: We enrolled
      210 patients with an exacerbation of chronic low back pain who reported current
      pain of 5 or more (out of 10) on a visual analog scale. They were randomly
      assigned to receive an oral willow bark extract with either 120 mg (low dose) or
      240 mg (high dose) of salicin, or placebo, with tramadol as the sole rescue
      medication, in a 4-week blinded trial. The principal outcome measure was the
      proportion of patients who were pain-free without tramadol for at least 5 days
      during the final week of the study. RESULTS: The treatment and placebo groups
      were similar at baseline in 114 of 120 clinical features. A total of 191 patients
      completed the study. The numbers of pain-free patients in the last week of
      treatment were 27 (39%) of 65 in the group receiving high-dose extract, 15 (21%)
      of 67 in the group receiving low-dose extract, and 4 (6%) of 59 in the placebo
      group (P <0.001). The response in the high-dose group was evident after only 1
      week of treatment. Significantly more patients in the placebo group required
      tramadol (P <0.001) during each week of the study. One patient suffered a severe
      allergic reaction, perhaps to the extract. CONCLUSION: Willow bark extract may be
      a useful and safe treatment for low back pain.

PMID- 10936473
TI  - Which venous leg ulcers will heal with limb compression bandages?
AB  - PURPOSE: To develop a simple prediction rule to identify patients in whom a
      venous leg ulcer will heal using a limb compression bandage (eg, Unna's boot).
      SUBJECTS AND METHODS: We performed a retrospective cohort study of patients with
      venous leg ulcers who received a limb compression bandage applied weekly.
      Prognostic factors were assessed from the patient's history before the start of
      treatment. The outcome of interest was a healed wound within 24 weeks of
      treatment. The final model was validated in another data set. RESULTS: Several
      accurate prognostic models were developed. The simplest model summed the size and
      duration of the wound before treatment, with 1 point given for a wound with an
      area >5 cm(2) and another if the wound was >6 months old. In the development data
      set, ulcers healed in 93% (110 of 118) of patients with a score of 0, but in only
      13% (9 of 67) of those with a score of 2. In the validation data set, ulcers
      healed in 95% (19 of 20) of patients with a score of 0, and 37% (44 of 120) of
      those with a score of 2. CONCLUSIONS: This simple prognostic model can be used to
      discriminate between patients with a venous leg ulcer that will or will not heal
      within 24 weeks of care with a limb compression bandage. The model may be useful
      in determining which patients to treat with a limb compression, and which
      patients should be referred or considered for alternative treatments.

PMID- 10936474
TI  - Association of smoking with abnormal exercise heart rate responses and long-term
      prognosis in a healthy, population-based cohort.
AB  - BACKGROUND: Cigarette smoking is associated with chronotropic incompetence,
      defined as an attenuated heart rate response to exercise. The long-term
      prognostic implications of this association have not been well explored. SUBJECTS
      AND METHODS: Adults enrolled in the Lipid Research Clinics' Prevalence Study who
      had no history of cardiovascular disease and who were not taking beta-blockers
      were observed for 12 years. Chronotropic incompetence was assessed as the failure
      to achieve 90% of an age-predicted target heart rate during an exercise test or
      as a low chronotropic index, a measure of exercise heart rate response adjusted
      for age, resting heart rate, and physical fitness. RESULTS: Of the 5,354 eligible
      participants (mean [+/- SD] age of 44 +/- 10 years; 61% male), 1,931 (36%) smoked
      cigarettes. Smokers were more likely to have a low chronotropic index (26% versus
      16%, odds ratio = 1.8, 95% confidence interval [CI] 1.6 to 2.1) and fail to
      achieve an age-predicted target heart rate (32% versus 22%, odds ratio = 1.7, 95%
      CI 1.5 to 2.0). Adjustment for standard cardiac risk factors and physical fitness
      did not affect these associations. During follow-up, there were 327 deaths. Among
      subjects without chronotropic incompetence, the relative risk of mortality
      associated with smoking was moderately increased (hazard ratio = 1.8, 95% CI 1.3
      to 2.3); among smokers with chronotropic incompetence, the relative risk of
      mortality was markedly increased (hazard ratio = 2.7, 95% CI 2.0 to 3.7, P for
      interaction = 0.02). CONCLUSIONS: In this large, middle-aged population-based
      cohort, smoking was associated with chronotropic incompetence, which in turn
      identified smokers with a particularly high mortality rate.

PMID- 10936475
TI  - Intravenous iron dextran therapy in patients with iron deficiency and normal
      renal function who failed to respond to or did not tolerate oral iron
      supplementation.
AB  - PURPOSE: To evaluate the safety and effectiveness of using 500-mg doses of iron
      as intravenous iron dextran after premedication with diphenhydramine, cimetidine,
      and dexamethasone. SUBJECTS AND METHODS: We treated 135 iron-deficient adults (26
      men, 109 women) with normal renal function (serum creatinine level </=1.5 mg/dL
      or blood urea nitrogen level </=26 mg/dL) who could not be treated adequately
      with oral iron supplements due to gastrointestinal symptoms (59%), inadequate
      hematologic response (39%), severe anemia (19%), or noncompliance (4%). Some
      patients had more than one reason for treatment. Resolution of iron deficiency
      was defined as the restoration of transferrin saturation, serum ferritin level,
      anemia, and abnormal erythrocyte indexes to normal or baseline values. RESULTS:
      Before treatment with iron dextran, patients had a mean (+/- SD) transferrin
      saturation of 8% +/- 5%, a median serum ferritin level of 11 ng/mL, and a mean
      hemoglobin level of 10 +/- 2 g/dL. Ninety-two percent were anemic; 60% had
      unrecognized or untreated causes of anemia other than iron deficiency. We
      administered 285 iron dextran infusions (median 2, mean 2 infusions per patient;
      range 1 to 7). Eighty-seven percent of patients had no adverse reaction; 13% had
      mild reactions, especially arthralgias and myalgias. No patient had an
      anaphylaxis-like reaction. Fifty-four (40%) patients had resolution of iron
      deficiency, 34 (25%) continue to receive therapy, 36 (27%) returned to the care
      of their primary physician, and 11 (8%) died before iron repletion could be
      achieved. CONCLUSIONS: Iron-deficient adults with normal renal function who
      cannot be treated adequately with oral iron supplements can be treated
      effectively and safely with this intravenous iron dextran regimen.

PMID- 10936476
TI  - Phagocytes and oxidative stress.
AB  - Neutrophils and other phagocytes manufacture O(2)(-) (superoxide) by the one
      electron reduction of oxygen at the expense of NADPH. Most of the O(2)(-) reacts
      with itself to form H(2)O(2) (hydrogen peroxide). From these agents a large
      number of highly reactive microbicidal oxidants are formed, including HOCl
      (hypochlorous acid), which is produced by the myeloperoxidase-catalyzed oxidation
      of Cl(-) by H(2)O(2); OH(*) (hydroxyl radical), produced by the reduction of
      H(2)O(2) by Fe(++) or Cu(+); ONOO(-) (peroxynitrite), formed by the reaction
      between O(2)(-) and NO(*); and many others. These reactive oxidants are
      manufactured for the purpose of killing invading microorganisms, but they also
      inflict damage on nearby tissues, and are thought to be of pathogenic
      significance in a large number of diseases. Included among these are emphysema,
      acute respiratory distress syndrome, atherosclerosis, reperfusion injury,
      malignancy and rheumatoid arthritis.

PMID- 10936477
TI  - Assessment of three schemes for stratifying stroke risk in patients with
      nonvalvular atrial fibrillation.
AB  - PURPOSE: The risk of ischemic stroke varies widely among patients with
      nonvalvular atrial fibrillation, influencing the choice of prophylactic
      antithrombotic therapy. We assessed three schemes for stroke risk stratification
      in these patients who were treated with aspirin and who did not have prior
      cerebral ischemia. SUBJECTS AND METHODS: Criteria from three schemes of risk
      stratification were applied to a longitudinally observed cohort of patients with
      atrial fibrillation who did not have prior cerebral ischemia and who were treated
      with aspirin alone or aspirin combined with low, ineffective doses of warfarin in
      a multicenter clinical trial. The ability of the schemes to identify patients at
      high (>/=6%), low (</=2%), and intermediate annual risks of ischemic stroke was
      assessed. RESULTS: During a mean follow-up of 1.8 years, 48 ischemic strokes
      occurred among 1,073 patients with atrial fibrillation who were taking aspirin
      (rate = 2.5 per 100 person-years). Each of the three schemes predicted stroke and
      disabling stroke, and successfully identified patients at low risk (observed
      stroke rates of 0.3 to 1.1 per 100 person-years), although the fractions of the
      cohort that were categorized as low risk varied from 14% to 45%. The observed
      rates of ischemic stroke among patients categorized as high risk ranged from 3.5
      to 7.2 per 100 person-years among the stratification schemes. Two schemes
      considered all patients >75 years old as high risk (observed stroke rate 4.2 per
      100 person-years), while the remaining scheme classified one third of patients in
      this age group as low risk (observed stroke rate 0.6 per 100 person-years).
      CONCLUSIONS: When tested in a large cohort of patients with atrial fibrillation
      who were treated with aspirin, available risk-stratification schemes successfully
      identified patients with low rates of ischemic stroke, but less consistently
      identified high-risk patients.

PMID- 10936478
TI  - Third-generation thrombolytic drugs.
AB  - Several third-generation thrombolytic agents have been developed. They are either
      conjugates of plasminogen activators with monoclonal antibodies against fibrin,
      platelets, or thrombomodulin; mutants, variants, and hybrids of alteplase and
      prourokinase (amediplase); or new molecules of animal (vampire bat) or bacterial
      (Staphylococcus aureus) origin. These variations may lengthen the drug's half
      life, increase resistance to plasma protease inhibitors, or cause more selective
      binding to fibrin. Compared with the second-generation agent (alteplase), third
      generation thrombolytic agents such as monteplase, tenecteplase, reteplase,
      lanoteplase, pamiteplase, and staphylokinase result in a greater angiographic
      patency rate in patients with acute myocardial infarction, although, thus far,
      mortality rates have been similar for those few drugs that have been studied in
      large-scale trials. Bleeding risk, however, may be greater.

PMID- 10936479
TI  - The abdominojugular reflux sign.
AB  - PURPOSE: The abdominojugular reflux sign is useful in diagnosing right
      ventricular failure, but is often performed and interpreted incorrectly. Our
      objective was to review the history, epidemiology, and pathophysiology of the
      abdominojugular reflux sign. METHODS: We conducted a MEDLINE search of the
      English language reports published between 1966 and 1999 and a manual search of
      bibliographies of relevant papers. RESULTS: A positive abdominojugular reflux
      sign is defined by an increase in the jugular venous pressure of greater than 3
      cm, sustained for greater than 15 seconds. In the absence of left heart failure,
      a positive abdominojugular reflux sign should prompt consideration of impaired
      right ventricular preload, a decrease in right ventricular compliance, a decrease
      in right ventricular systolic function or an elevation in right ventricular
      afterload. In patients presenting with dyspnea, the abdominojugular reflux is
      useful in predicting congestive heart failure (LR+ 6.0 (95% CI; 0.8-51); LR-
      0.78; (95% CI: 0.62 to 0.98)) and suggests pulmonary capillary wedge pressures of
      greater than 15 mm Hg (LR+ 6. 7 (95% CI: 3.3 to 13.4); LR- 0.08 (95% CI: 0.01 to
      0.52)). CONCLUSION: The abdominojugular reflux is not specific to any one
      disorder, but rather is a reflection of a right ventricle that cannot accommodate
      augmented venous return. Constrictive pericarditis, right ventricular infarction,
      and restrictive cardiomyopathy are common causes of a positive finding. Left
      ventricular failure may also induce the sign, but only when the pulmonary
      capillary wedge pressure is greater than 15. The one diagnosis not seen with
      abdominojugular reflux is cardiac tamponade.

PMID- 10936480
TI  - Liver biopsy in the evaluation of patients with chronic hepatitis C who have
      repeatedly normal or near-normal serum alanine aminotransferase levels.

PMID- 10936481
TI  - Case of the month
AB  - Each month, we will present a challenging Case of the Month for The Green Journal
      readers, who must use their clinical acumen to arrive at the correct answer. We
      will also post the case each month on the Journal's web site
      (http://www.elsevier.com/locate/ajmselect). Several possible answers may be
      consistent with the case presentation; use your best judgment. Please send your
      answer (one per respondent) and indicate the case to which you are responding to
      The Green Journal at editors@amjmed.org or via FAX to (415) 447-2799. Only those
      answers with a complete mailing address will be considered. The correct answer
      will appear in the August issue of the Journal. The first five persons who submit
      correct answers will receive a free one-year subscription to the Journal.
      Colleagues of Dr. Hirsch in Ann Arbor, Michigan, are not eligible for this
      month's case. If you would like to contribute a case, please submit a brief
      synopsis (<250 words) to the editorial office. An individual may win only once
      per calendar year.

PMID- 10936482
TI  - The dilemma of disease progression in hepatitis C patients with normal serum
      aminotransferase levels.

PMID- 10936483
TI  - Association of Professors of Medicine. Ethical issues in clinical research: an
      issue for all internists.

PMID- 10936484
TI  - Peroxisome proliferator-activated receptor and retinoid X receptor ligands
      inhibit monocyte chemotactic protein-1-directed migration of monocytes.
AB  - Monocyte chemotactic protein-1 (MCP-1)-directed transendothelial migration of
      monocytes plays a key role in the development of inflammatory diseases.
      Infiltration of tissues by monocytes requires degradation of extracellular
      matrices, a process that involves matrix metalloproteinases. We studied the
      effects of peroxisome proliferator-activated receptor (PPAR) gamma, alpha, and
      retinoid X receptor alpha (RXRalpha) ligands on MCP-1-directed migration and
      matrix metalloproteinase expression of a human acute monocytic leukemia cell line
      (THP-1). PPARgamma ligands attenuated MCP-1-induced migration, with 50%
      inhibition (IC(50)) at 2.8 microM for troglitazone and 4.8 microM for
      rosiglitazone. PPARalpha ligands WY-14643 (IC(50): 0.9 microM) and 5,8,11,14
      eicosatetranoic acid (IC(50): 9.9 microM), and the potent RXRalpha ligand AGN
      4204 (IC(50): 3.6 nM) also blocked monocyte migration. Troglitazone,
      rosiglitazone, or AGN 4204 inhibited phorbol 12-myristate 13-acetate (PMA)
      induced matrix metalloproteinase-9 expression. PPARalpha activators WY-14643 and
      5,8,11,14-eicosatetraynoic acid, however, had no inhibitory effect. AGN 4204
      increased PMA-induced tissue inhibitor of matrix metalloproteinases-1 (TIMP-1)
      expression, whereas all PPAR ligands showed no effect. All PPAR and RXRalpha
      ligands blocked chemotaxis of THP-1 monocytes in the absence of a matrix barrier.
      This study demonstrates that activated PPARs and RXRalpha, block MCP-1-directed
      monocyte migration, mediated, at least in part, through their effects on matrix
      metalloproteinase-9 or TIMP-1 production, or chemotaxis.

PMID- 10936485
TI  - Determinants of recognition of ligands binding to benzodiazepine receptor/GABA(A)
      receptors initiating sedation.
AB  - Complementary behavioral and computational studies of 21 structurally diverse,
      gamma-amino butyric acid (GABA)(A) benzodiazepine receptor ligands that influence
      spontaneous locomotor activity have been performed in this work. This behavioral
      endpoint is a well-accepted indicator of sedation particularly for
      GABA(A)/benzodiazepine receptor ligands. The goal of the work presented here is
      the identification and assessment of the minimum requirements for ligand
      recognition of GABA(A)/benzodiazepine receptors leading to activity at the
      sedation endpoint embedded in a common 3D pharmacophore for recognition. Using
      the experimental results, together with a systematic computational procedure
      developed in our laboratory, a five-component 3D pharmacophore for recognition of
      the GABA(A) receptor subtypes associated with the sedative behavioral response
      has been developed consisting of: two proton-accepting moieties, a hydrophobic
      region, a ring with polar moieties and an aromatic ring in a common geometric
      arrangement in all ligands having an effect at the sedation endpoint. To provide
      further evidence that the 3D pharmacophore developed embodied common requirements
      for receptor recognition, a pharmacophore analysis was performed for agonists,
      inverse agonists and antagonists separately. Each of the resulting pharmacophores
      contained the same five moieties at comparable distances to those found for the
      pharmacophore generated using all of them together. This result confirms that
      this pharmacophore constitutes a recognition pharmacophore representing required
      features in the overlapping portion of their binding sites. The reliability of
      this 3D pharmacophore was then assessed in several ways. First, it was determined
      that ligands that had no effect at the sedation endpoint did not comply with the
      pharmacophore requirements. Second, four benzodiazepine receptor ligands known to
      have an effect at the sedation endpoint, but not used in the pharmacophore
      development were found to satisfy the requirements of this pharmacophore. Third,
      the geometric and chemical requirements embedded in this pharmacophore were used
      to search 3D databases resulting in the identification of benzodiazepine receptor
      ligands known to affect sedation, but not included in the pharmacophore
      development. Finally, a 3D-quantitative structure analysis procedure (QSAR) model
      was developed based upon the ligands in the training set superimposed at their
      sedation pharmacophore points. The 3D-QSAR model shows good predictivity for
      binding of these ligands to receptor subtypes containing alpha1 but not alpha5
      subunits. The pharmacophore developed for the sedation endpoint thus provides a
      predictive binding model for diverse ligand binding to alpha1 containing receptor
      subtypes.

PMID- 10936486
TI  - Evidence that atypical vasopressin V(2) receptor in inner medulla of kidney is
      V(1B) receptor.
AB  - Vasopressin V(2) receptors at high-density and V(1B) receptors are candidates for
      the V(2)-like receptor, which evokes an increase in [Ca(2+)](i) when stimulated
      by the vasopressin V(2) receptor agonist 1-desamino-8-D-arginine vasopressin
      (dDAVP) in kidney inner medullary collecting duct. We compared the
      pharmacological characteristics of vasopressin V(2) and V(1B) receptors in
      Chinese hamster ovary (CHO) cells to those of vasopressin V(2)-like receptors in
      rat inner medullary collecting duct cells. The vasopressin V(1B) receptor
      selective agonist [deamino-Cys(1), D-3-(Pyridyl)-Ala(2), Arg(8)]vasopressin
      (D3PVP) did not stimulate the [Ca(2+)](i) increase in high-density vasopressin
      V(2) receptor-expressing CHO cells, but did in inner medullary collecting duct
      cells. Moreover, the vasopressin V(1A)/V(2) receptor dual antagonist 4'-[(2
      methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1] benzazepin-6-yl)carbonyl] 2
      phenylbenzanilide (YM087), which has no effect on vasopressin V(1B) receptors,
      did not block the [Ca(2+)](i) increase in inner medullary collecting duct cells
      when stimulated by dDAVP and D3PVP. On reverse transcription-polymerase chain
      reaction (RT-PCR) analysis of kidney, vasopressin V(1B) receptor mRNA was
      detected only in the medulla. We propose that the true nature of the vasopressin
      V(2)-like receptor in the inner medullary collecting duct is the vasopressin
      V(1B) receptor, rather than the vasopressin V(2) receptor expressed at high
      density.

PMID- 10936487
TI  - Amitriptyline modulation of Na(+) channels in rat dorsal root ganglion neurons.
AB  - The effects of amitriptyline, a tricyclic antidepressant, on tetrodotoxin
      sensitive and tetrodotoxin-resistant Na(+) currents in rat dorsal root ganglion
      neurons were studied using the whole-cell patch clamp method. Amitriptyline
      blocked both types of Na(+)currents in a dose-and holding potential-dependent
      manner. At the holding potential of -80 mV, the apparent dissociation constants
      (K(d)) for amitriptyline to block tetrodotoxin-sensitive and tetrodotoxin
      resistant Na(+) channels were 4.7 and 105 microM, respectively. These values
      increased to 181 and 193 microM, respectively, when the membrane was held at a
      potential negative enough to remove the steady-state inactivation. Amitriptyline
      dose-dependently shifted the steady-state inactivation curves in the
      hyperpolarizing direction and increased the values of the slope factors for both
      types of Na(+) channels. The voltage dependence of the activation of both types
      of Na(+) channels was shifted in the depolarizing direction. It was concluded
      that amitriptyline blocked the two types of Na(+) channels in rat sensory neurons
      by modulating the activation and the inactivation kinetics.

PMID- 10936488
TI  - Repeated haloperidol treatment decreases sigma(1) receptor binding but does not
      affect its mRNA levels in the guinea pig or rat brain.
AB  - The effects of chronic treatment with haloperidol on sigma (sigma) receptors were
      investigated across brain regions and species. The regional distribution of
      [3H](+)-pentazocine binding to sigma(1) receptor was similar between the guinea
      pig and rat brains. The highest level of binding was detected in the brain stem
      and lowest in the striatum and hippocampus. The regional distribution of [3H]1, 3
      di (2-tolyl) guanidine ([3H]DTG) binding in the presence of 100 nM (+)
      pentazocine to sigma(2) receptor was similar to that of the [3H](+)-pentazocine
      binding in the guinea pig brain, while in the rat brain high levels of [3H]DTG
      binding were detected in the cortex, frontal cortex and cerebellum. The
      intraperitoneal administration of 2 mg/kg of haloperidol to guinea pig and rats
      once a day for 21 days produced inhibition of [3H](+)-pentazocine binding but did
      not affect [3H]DTG binding to sigma(2) receptors in any brain region examined.
      The effects of haloperidol on [3H](+)-penazocine binding in the rat were much
      weaker than those in the guinea pig. The regional distribution of the level of
      sigma(1) receptor mRNA determined by the ribonuclease protection assay was
      similar to that of the [3H](+)-pentazocine binding activity, except in the cortex
      and cerebellum where the levels of sigma(1) receptor mRNA were low in guinea pig
      and rat. Treatment with haloperidol did not affect the levels of sigma(1)
      receptor mRNA in any brain region in either species. These findings suggested
      that the sigma receptors differentially distributed in brain regions are down
      regulated by treatment with haloperidol across sigma receptor subtypes and animal
      species without changing the transcriptional activity of the sigma(1) receptor.
      The mechanisms by which sigma receptors could be differently regulated in vivo by
      chronic treatment with haloperidol in different species may contribute to the
      therapeutic efficacy of haloperidol.

PMID- 10936489
TI  - Lead stimulates intercellular signalling between hepatocytes and Kupffer cells.
AB  - The role of intercellular signalling between liver cells in lead (Pb)(1)-induced
      liver toxicity was investigated in cocultures of freshly isolated and cultured
      rat hepatocytes and Kupffer cells. The Kupffer cells (seeded onto culture dish
      inserts), the hepatocytes or the two in cocultures were exposed to Pb acetate (2
      50 microM) in combination with lipopolysaccharide (0.1-1000 ng/ml). In hepatocyte
      cultures, the combined Pb/lipopolysaccharide treatment induced no significant
      increase in the release of the proinflammatory cytokine tumor necrosis factor
      alpha (TNF-alpha) whereas in Kupffer cell cultures and in cocultures, at low
      lipopolysaccharide levels (0.1 and 1 ng/ml), TNF-alpha release was
      synergistically increased (up to 30-fold) when compared to lipopolysaccharide
      exposure alone. This stimulation of Kupffer cell-derived TNF-alpha release was
      specific for Pb or not detectable with mercury and cadmium. As a response to the
      Pb/lipopolysaccharide induced release of TNF-alpha, the cocultured hepatocytes
      increased their nitric oxide (NO) content sixfold when compared with
      lipopolysaccharide alone and downregulated the negatively regulated acute phase
      protein albumin. This downregulation was also detectable without
      lipopolysaccharide and without TNF-alpha release, indicating that Pb induces
      additional thus far unidentified Kupffer cell-derived factors, which interact
      with the cocultured hepatocytes. At the time of TNF-alpha release, the viability
      of the hepatocytes and the Kupffer cells was not affected. However, after a 48-h
      treatment period, Pb induced a Kupffer cell specific toxicity without affecting
      the hepatocytes. Loss of hepatocyte viability after lipopolysaccharide/Pb
      stimulation was only detectable in the presence of cocultured Kupffer cells
      together with human-derived granulocytes. It is concluded that Pb stimulates
      intercellular signalling between Kupffer cells and hepatocytes which is
      synergistically enhanced in the presence of low lipopolysaccharide levels. The
      released Kupffer cell-derived signals (e.g. cytokines) promotes most likely
      proteolytic hepatocyte killing in combination with a direct cellular interaction
      between the granulocytes and the hepatocytes.

PMID- 10936490
TI  - The alpha and gamma subunit-dependent effects of local anesthetics on recombinant
      GABA(A) receptors.
AB  - Although convulsions due to local anesthetic systemic toxicity are thought to be
      due to inhibition of GABA(A) receptor-linked currents in the central nervous
      system, the mechanism of action remains unclear. We therefore examined the
      effects of local anesthetics on gamma-aminobutyric acid (GABA)-induced currents
      using recombinant GABA(A) receptors with specific combinations of subunits.
      Murine GABA(A) receptors were expressed by injection of cRNAs encoding each
      subunit into Xenopus oocytes. The effects of local anesthetics (lidocaine,
      bupivacaine, procaine and tetracaine) on GABA-induced currents of receptors
      expressing different subunit combinations (alpha1beta2, alpha1beta2gamma2s,
      alpha4beta2gamma2s and beta2) were examined via the two electrode voltage clamp
      method. At alpha1beta2, alpha1beta2gamma2s and alpha4beta2gamma2s GABA(A)
      receptors, all local anesthetics inhibited GABA-induced currents in a dose
      dependent manner. The presence of the gamma2s subunit resulted in a greater
      inhibition by all local anesthetics, but the presence of the alpha4 subunit
      resulted in less inhibition. At beta2 homomeric receptors, local anesthetics
      directly induced an outward current similar to that of picrotoxin. These data
      indicated that (1) the alpha and gamma subunits of GABA(A) receptors modulated
      the inhibitory effects of local anesthetics on GABA(A) function, and (2) local
      anesthetics can activate the beta2 subunit and may block the GABA(A) receptor
      channel pore.

PMID- 10936491
TI  - Modulation of gamma-aminobutyric acid responses in the rat optic nerve.
AB  - Depolarising GABA(A) receptor-mediated responses recorded from the optic nerve
      using a grease gap technique were modulated by classical potentiators of GABA(A)
      receptors. The benzodiazepine, chlordiazepoxide, the barbiturate, pentobarbitone
      and the widely used anaesthetic, propofol, all potentiated gamma-aminobutyric
      acid (GABA) responses. They did so with different maximal efficacies,
      propofol>pentobarbitone>chlordiazepoxide, and potencies on the basis of EC(50)
      estimates, chlordiazepoxide>propofol>pentobarbitone. The greater than expected
      GABA potentiating properties of propofol were explained by a direct
      hyperpolarising action that occurred in the same concentration range as its
      action at the GABA(A) receptor but that was unlikely to be mediated by GABA(A)
      receptors.

PMID- 10936492
TI  - Atrial natriuretic peptide modulates N-methyl-D-aspartate-induced
      hyperexcitability in ethanol-dependent mice.
AB  - The role of central nervous atrial natriuretic peptide was investigated for
      behavioral hyperexcitability in alcohol-dependent mice. Mice were made tolerant
      to and dependent on ethanol with an ethanol-liquid diet for 14 days. Five hours
      after withdrawal from ethanol, withdrawal symptoms were analyzed by scoring
      handling-induced convulsions. N-methyl-D-aspartate (NMDA) induced behavioral
      seizures in a dose-dependent manner, an effect which was more intensive during
      the ethanol withdrawal period than in alcohol-naive animals.
      Intracerebroventricular (i.c.v.) injections of alpha-atrial natriuretic peptide
      (atrial natriuretic peptide) dose-dependently inhibited, whereas injection of an
      antiserum against atrial natriuretic peptide potentiated, the seizure-inducing
      effect of NMDA in ethanol-dependent mice. The main conclusion is that central
      nervous atrial natriuretic peptide plays a modulatory role in behavioral
      hyperexcitability during alcohol withdrawal.

PMID- 10936493
TI  - Erythropoietin protects against brain ischemic injury by inhibition of nitric
      oxide formation.
AB  - Erythropoietin prevents in vitro glutamate-induced neuronal death and could play
      a role in the central nervous system. We investigated the in vivo effects of
      recombinant human erythropoietin after intraperitoneal (i.p.; 25-100 U) or
      intracerebroventricular (i.c.v.; 0.25-25 U) administration on survival, brain
      malonildialdehyde (MDA) levels, brain edema, hippocampal neuronal death and brain
      nitric oxide (NO) synthesis after bilateral carotid occlusion (5 min), followed
      by reperfusion in the Mongolian gerbil. Peripheral posttreatment with recombinant
      human erythropoietin reduced postischemic MDA levels, brain edema and increased
      survival. Either peripheral or i.c.v. posttreatment with recombinant human
      erythropoietin significantly reduced hippocampal CA1 neuronal loss, observed 7
      days after the ischemic event. Increase of nitrite and nitrate (as an index of NO
      formation) in the hippocampus, as observed after ischemia, was reduced in animals
      treated with recombinant human erythropoietin. These data suggest that in vivo
      recombinant human erythropoietin effects on brain ischemic injury could be due to
      inhibition of NO overproduction.

PMID- 10936494
TI  - Estrogen priming modulates autoreceptor-mediated potentiation of dopamine uptake.
AB  - The ability of a physiological dose of estrogen (estradiol benzoate, estrogen: 10
      microgram 48 and 24 h prior) to modulate autoreceptor-mediated changes in
      dopamine transport properties was investigated in a synaptosomal preparation
      prepared from the nucleus accumbens of ovariectomized rats. Quinpirole (1-100
      microM)-mediated potentiation of [3H]dopamine uptake was attenuated in
      synaptosomes from estrogen-primed animals. Haloperidol (10 microM) inhibited
      basal uptake and effectively prevented quinpirole potentiation of uptake in both
      ovariectomized and estrogen-primed samples. The ability of selective protein
      phosphatase inhibitors to modulate autoreceptor-mediated potentiation of dopamine
      uptake was also examined. Pretreatment with protein phosphatase 2B (deltamethrin,
      cypermethrin) or protein phosphatase 1 (tautomycin) inhibitors attenuated basal
      and quinpirole-potentiated dopamine uptake in ovariectomized but not estrogen
      primed tissue. These data suggest that autoreceptor-mediated activation of
      dopamine transport can be regulated by physiological doses of estrogen and
      implicate a role for protein phosphorylation in autoreceptor-mediated
      potentiation of dopamine uptake.

PMID- 10936495
TI  - Ethanol modulates evoked dopamine release in mouse nucleus accumbens: dependence
      on social stress and dose.
AB  - Ethanol may modulate the activity of presynaptic terminals to increase
      extracellular dopamine release in the nucleus accumbens though conflicting
      results have been published. It has been suggested that the stress of social
      defeat might be a factor influencing the effects of ethanol. We investigated the
      effects of ethanol on the evoked dopamine overflow in the nucleus accumbens in
      anaesthetised mice by in vivo voltammetry. Dominant animals, subordinates which
      had been defeated following eight intruder-resident encounters, and subordinate
      nondefeated mice were used. The overflow was evoked by electrical stimulation of
      the median forebrain bundle (100 pulses) at low (20 Hz) and high (50 Hz)
      frequencies of stimulation. Ethanol at 0.1 and 2 g/kg had no effects on evoked
      dopamine overflow in aggressive and nondefeated mice. Ethanol increased dopamine
      release at 0.1 g/kg and decreased release at 2 g/kg following high frequency
      stimulation in defeated mice. These data suggest that the stress of social defeat
      may have sensitised the machinery involved in dopamine release to ethanol, a
      process that may increase the reinforcing properties of this compound.

PMID- 10936496
TI  - Decreased opioid-induced antinociception but unaltered G-protein activation in
      the genetic-diabetic NOD mouse.
AB  - Previous evaluation of antinociceptive action in experimental diabetes has been
      conducted almost exclusively in chemically induced diabetes mellitus. The purpose
      of the present study was to evaluate antinociceptive response and G-protein
      activation by mu-opioid receptor and delta-opioid receptor agonists in the
      genetic non-obese diabetic (NOD) mouse, a model of type I insulin-dependent
      diabetes mellitus (IDDM). Tail-flick latency before and after hyperglycemia was
      unaltered. Hyperglycemic NOD mice were hyporesponsive to intracerebroventricular
      (i.c.v.) injections of [D-Ala(2)]deltorphin II but not to [D-Ala(2), N-MePhe(4),
      Gly-ol(5)]enkephalin (DAMGO); however, G-protein activation in pons/medulla
      assessed by [35S]GTPgammaS binding was not diminished. This suggests that a G
      protein defect in signaling cannot account for the hyporesponsiveness of
      antinociception in this genetic model of IDDM.

PMID- 10936497
TI  - Antagonist resistant contractions of the porcine pulmonary artery by cysteinyl
      leukotrienes.
AB  - The contractile response to cysteinyl-leukotrienes was studied in isolated
      porcine pulmonary arterial rings. In endothelium-denuded preparations, the
      concentration-response curves for leukotriene C(4) and leukotriene D(4) were
      identical, whereas leukotriene E(4) did not contract these tissues. The response
      to leukotriene C(4) was not blocked by either CysLT(1)/CysLT(2) receptor
      antagonism or by pre-treatment with leukotriene E(4). In preparations with an
      intact endothelium, leukotriene C(4) was somewhat more potent than leukotriene
      D(4) and the concentration-response curves were only slightly depressed in the
      presence of either ICI 204,219 (4-(5-cyclopentyloxycarbonylamino-1-methylindol-3
      ylmethy l)-3-methoxy -N-o-tolylsulfonylbenzamide, 1 microM) or BAY u9773 (6(R)
      (4'-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E), 11(Z)14(Z)-eicosatetrenoic acid, 3
      microM). Indomethacin (1.7 microM) significantly reduced the response to
      leukotriene C(4) whereas the response to leukotriene D(4) was unchanged. These
      findings suggest that a CysLT receptor subtype resistant to current antagonists
      mediated the major part of the contractions to leukotriene C(4) and leukotriene
      D(4) in intact preparations, and was the sole receptor associated with
      contractions of endothelium-denuded preparations.

PMID- 10936498
TI  - Prostacyclin modulation of contractions of the human pulmonary artery by
      cysteinyl-leukotrienes.
AB  - The contractile response to cysteinyl-leukotrienes was studied in isolated human
      pulmonary arterial rings. Concentration-response curves for leukotriene C(4) were
      significantly potentiated by the cyclooxygenase inhibitor indomethacin (1.7
      microM) and after endothelial denudation. Measurements of 6-keto prostaglandin
      F(1alpha) showed that cysteinyl-leukotrienes stimulated the release of
      prostacyclin. A single concentration (1 microM) of either leukotriene C(4) or
      leukotriene D(4) resulted in both contraction and relaxation. Indomethacin
      abolished the relaxant phase and enhanced the amplitude of the contraction,
      supporting that cysteinyl-leukotriene-induced contractions of the human pulmonary
      artery may be functionally antagonised by the release of prostacyclin. The
      contractions induced by leukotriene C(4) were resistant to the two cysteinyl
      leukotriene receptor antagonists MK 571 ((3-(-2(7-chloro-2
      quinolinyl)ethenyl)phenyl)((3-(dimethylamino-3-oxo propyl)thio)methyl)thio
      propanoic acid, 1 microM) and BAY u9773 (6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy
      7(E),9(E), 11(Z)14(Z)-eicosatetrenoic acid, 3 microM), both in the absence and
      presence of indomethacin. These findings suggest a functional cysteinyl
      leukotriene receptor in the human pulmonary artery with antagonist properties not
      previously described in human tissue.

PMID- 10936499
TI  - Diabetes-induced changes in endothelial mechanisms implicated in rabbit carotid
      arterial response to 5-hydroxytryptamine.
AB  - The influence of diabetes on endothelial mechanisms implicated in the response of
      isolated rabbit carotid arteries to 5-hydroxytryptamine (5-HT) was studied. 5-HT
      induced a concentration-dependent contraction that was potentiated in arteries
      from diabetic rabbits with respect to that in arteries from control rabbits.
      Endothelium removal potentiated 5-HT contractions in arteries from both control
      and diabetic rabbits but increased the maximum effect only in arteries from
      diabetic rabbits. Incubation of arterial segments with N(G)-nitro-L-arginine (L
      NA) enhanced the contractile response to 5-HT. This L-NA enhancement was greater
      in arteries from diabetic rabbits than in arteries from control rabbits.
      Aminoguanidine did not modify the 5-HT contraction in arteries from control and
      diabetic rabbits. Indomethacin inhibited the 5-HT-induced response, and this
      inhibition was higher in arteries from control rabbits than in arteries from
      diabetic rabbits. In summary, diabetes enhances the sensitivity of the rabbit
      carotid artery to 5-HT. In control animals, the endothelium modulated the
      arterial response to 5-HT by the release of both nitric oxide (NO) and a
      vasoconstrictor prostanoid. Diabetes enhances endothelial constitutive NO
      activity and impairs the production of the endothelial vasoconstrictor.

PMID- 10936500
TI  - Role of Cl(-) channels in alpha-adrenoceptor-mediated vasoconstriction in the
      anesthetized rat.
AB  - In vitro studies have provided evidence that Cl(-) ion currents are important for
      activation of vascular smooth muscle contraction. The stilbene, 4,4'
      diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), disrupts Cl(-) metabolism
      by blocking Cl(-) channels and by inhibiting Cl(-) bicarbonate exchange. The aims
      of this study were to: (i) characterize the hemodynamic responses produced by
      DIDS in pentobarbital anesthetized rats, and (ii) examine vasoconstrictor
      responses to norepinephrine before and after administration of DIDS. DIDS (2.5-50
      micromol/kg, 92.5 micromol/kg total dose, i.v.) produced dose-dependent but
      transient reductions in mean arterial blood pressure and in hindquarter, renal
      and mesenteric vascular resistances. Prior to the administration of DIDS,
      norepinephrine (1. 0-5.0 microgram/kg, i.v.) produced dose-dependent increases in
      mean arterial pressure, renal resistance and mesenteric resistance, but decreases
      in hindquarter resistance that were inversely related to dose. After
      administration of DIDS, the peak pressor responses produced by norepinephrine
      were either slightly diminished (1.0, 2.5 microgram/kg) or unchanged (5.0
      microgram/kg). Peak norepinephrine-induced changes in hindquarter and renal
      vascular resistance were unaffected by DIDS, while increases in mesenteric
      resistance were augmented. The total norepinephrine-induced increases in mean
      arterial pressure (mm Hgxs) were markedly reduced by DIDS. These effects of DIDS
      on norepinephrine-induced responses were similar, but not identical to those of
      the voltage-sensitive Ca(2+) channel blocker, nifedipine (500 nmol/kg, i.v.).
      These findings suggest that DIDS may interfere with norepinephrine-induced
      depolarization of resistance arteries, thereby preventing activation of voltage
      sensitive Ca(2+) channels.

PMID- 10936501
TI  - Z-335, a new thromboxane A(2) receptor antagonist, prevents arterial thrombosis
      induced by ferric chloride in rats.
AB  - We examined the antithrombotic effect of Z-335 ((+/-)-sodium [2-(4
      chlorophenylsulfonylaminomethyl)indan-5-yl]acetate monohydrate), an orally active
      thromboxane A(2) receptor (TP-receptor) antagonist that ameliorates experimental
      gangrene, using a rat arterial thrombosis model. The thrombi were induced by
      topical application of 50% ferric chloride solution to the rats abdominal artery.
      Z-335 (0.3-3 mg/kg, p.o.) inhibited thrombus formation in a dose-dependent
      manner. The antithrombotic effect of Z-335 (1 and 3 mg/kg, p.o.) was almost
      equivalent with that of cilostazol (100 mg/kg, p.o.), a selective
      phosphodiesterase type III inhibitor. The effect of Z-335 (3 mg/kg, p.o.), but
      not cilostazol, persisted for 16 h. Z-335, but not cilostazol, inhibited platelet
      aggregation induced by U-46619 (a TP-receptor agonist, 9, 11-dideoxy
      9alpha,11alpha-methanoepoxy prostaglandin F(2alpha)) for 16 h in rat whole blood.
      Histopathological examination also revealed that Z-335 prevented ferric chloride
      induced thrombus formation. These results suggest that Z-335 may prevent ferric
      chloride-induced arterial thrombosis through its antiplatelet action by blocking
      TP-receptor activation.

PMID- 10936502
TI  - Characterisation of SB-221420-A - a neuronal Ca(2+) and Na(+) channel antagonist
      in experimental models of stroke.
AB  - For progression to clinical trials in stroke, putative neuroprotective compounds
      should show robust efficacy post-ischaemia in several experimental models of
      stroke. This paper describes the characterisation of (+)(1S, 2R)-cis-1-[4-(1
      methyl-1-phenylethyl)phenoxy]-2-methylamino indane hydrochloride (SB-221420-A), a
      Ca(2+) and Na(+) channel antagonist. SB-221420-A inhibited (IC(50)=2.2 microM) N
      type voltage-operated Ca(2+) channel currents in cultured superior cervical
      ganglion neurons, which were pretreated with 10 microM nimodipine to block L-type
      voltage-operated Ca(2+) channel currents. In dorsal root ganglion neurons
      pretreated with 1 microM omega-conotoxin GVIA to block N-type voltage-operated
      Ca(2+) channel currents, SB-221420-A inhibited the residual Ca(2+) current with
      an IC(50) of 7 microM. SB-221420-A also inhibited Na(+) currents in dorsal root
      ganglion neurons with an IC(50) of 8 microM. In rats, the pharmacokinetic profile
      of SB-221420-A shows that it has a half-life of 6.4 h, a high volume of
      distribution, is highly brain penetrating, and has no persistent metabolites.
      Following bilateral carotid artery occlusion in gerbils, SB-221420-A
      significantly reduced the level of ischaemia-induced hyperlocomotor activity and
      the extent of hippocampal CA1 cell loss compared to the ischaemic vehicle-treated
      group. SB-221420-A was also effective in focal models of ischaemia. In the mouse
      permanent middle cerebral artery occlusion model, SB-221420-A (10 mg/kg)
      administered intravenously, post-ischaemia significantly (P<0.05) reduced lesion
      volume compared to the ischaemic vehicle-treated group. In the normotensive rat
      permanent middle cerebral artery occlusion model, SB-221420-A (10 mg/kg)
      administered intravenously over 1 h, beginning 30 min postmiddle cerebral artery
      occlusion, significantly (P<0.05) reduced lesion volume from 291+/-16 to 153+/-30
      mm(3), compared to ischaemic vehicle-treated controls when measured 24 h
      postmiddle cerebral artery occlusion. Efficacy was maintained when the same total
      dose of SB-221420-A was infused over a 6-h period, beginning 30 min postmiddle
      cerebral artery occlusion. SB-221420-A also significantly (P<0.05) reduced lesion
      volume following transient middle cerebral artery occlusion in normotensive rats
      and permanent middle cerebral artery occlusion in spontaneously hypertensive rats
      (SHR). Investigation of the side effect profile using the Irwin screen in mice
      revealed that, at neuroprotective doses, there were no overt behavioural or
      cardiovascular changes. These data demonstrate that robust neuroprotection can be
      seen post-ischaemia with SB-221420-A in both global and focal ischaemia with no
      adverse effects at neuroprotective doses, and indicate the potential utility of a
      mixed cation blocker to improve outcome in cerebral ischaemia.

PMID- 10936503
TI  - 4'-Hydroxy aceclofenac suppresses the interleukin-1-induced production of
      promatrix metalloproteinases and release of sulfated-glycosaminoglycans from
      rabbit articular chondrocytes.
AB  - This study demonstrates the novel actions of a non-steroidal anti-inflammatory
      drug aceclofenac, which is frequently used for rheumatoid arthritis and
      osteoarthritis. 4'-Hydroxy aceclofenac, a main metabolite of aceclofenac in
      humans, down-regulated the production of promatrix metalloproteinase
      1/procollagenase 1 and promatrix metalloproteinase-3/prostromelysin 1 along with
      a decrease in their mRNAs in rabbit articular chondrocytes and synoviocytes, and
      interfered with the release of sulfated-glycosaminoglycans (proteoglycans) from
      the chondrocytes. 4'-Hydroxy aceclofenac also suppressed the proliferation of
      rabbit synoviocytes. In contrast, aceclofenac itself and its other metabolites,
      diclofenac and 4'-hydroxy declofenac, did not exert obvious actions on cellular
      functions. Therefore, it is suggested that the therapeutic effects of aceclofenac
      on rheumatoid arthritis and osteoarthrits are, at least in part, due to the novel
      chondroprotective effect of 4'-hydroxy aceclofenac via the suppression of
      promatrix metalloproteinase production and proteoglycan release. There is also
      evidence that inhibition of synoviocyte proliferation and the known inhibitory
      action on prostaglandin E(2) production play a role.

PMID- 10936504
TI  - Aging enhances G(1) phase in the colonic mucosa of rats.
AB  - Although in Fischer-344 rats, aging has been shown to be associated with
      increased crypt cell production in the colonic mucosa, no information is
      available about the responsible intracellular mechanisms for the age-related rise
      in colonic mucosal cell proliferation. To determine whether cell cycling events
      are affected by aging, the present investigation examines the age-related changes
      in Cdk2 activity and the regulation of this process in the colonic mucosa.
      Colonic mucosae from 4-, 13- and 24-month-old Fischer-344 rats were assayed for
      Cdk2 activity and protein expression of Cdk2, cyclin D1 and E, as well as
      p21(Waf1/Cip1) (total and the fraction bound to Cdk2), p53 and phosphorylated Rb.
      Kinase activity and protein levels of Cdk2, as well as cyclin D1 concentration in
      the colonic mucosa, rose steadily with advancing age. However, the levels of
      cyclin E in the colonic mucosa were found to be higher in 24-month-old than 13
      month-old rats, compared to their 4-month-old counterparts. On the other hand,
      levels of mucosal p21(Waf1/Cip1) (total and the fraction bound to Cdk2), one of
      the universal inhibitors of Cdks, were found to be lower in aged than in young
      rats. This was accompanied by a parallel decrease in mucosal p53, a tumor
      suppressor protein that is known to regulate p21(Waf1/Cip1). Additionally, we
      observed that the levels of phosphorylated Rb protein, a form which is involved
      in regulating progression of cells through the S phase, are increased in the
      colonic mucosa of 24-month-old rats, but not in 13-month-old animals, when
      compared with their 4-month-old counterparts. Our data suggest that, G(1) to S
      phase transition, as well as progression through the S phase of the cell cycle
      are accelerated in the colonic mucosa of aged rats.

PMID- 10936505
TI  - Effects of fasting and exogenous glucose delivery on cardiac tolerance to low
      flow ischemia in adult and senescent rats.
AB  - Metabolic disorders due to changes in cytosolic glucose utilisation are suspected
      to be involved in the increased sensitivity of the aged myocardium to ischemia.
      This study presents the first direct measurement of glucose utilisation in hearts
      from senescent rats during low-flow ischemia under different conditions of
      substrate delivery and glycogen stores. Isolated hearts from young adult (4
      months-old) and senescent (24-months-old) rats were subjected to 30 min coronary
      flow restriction (residual flow rate=2% of control flows). Experiments were
      performed using glucose-free or glucose-enriched (11 mmol/L) perfusion media. The
      effects of increased glycogen stores were assessed after 24-h fasting in both age
      groups. Ischemic contracture was measured via a left-ventricular balloon. Ageing
      increased ischemic contracture under both conditions of substrate delivery in fed
      rat hearts. The increase in ischemic tolerance induced by fasting in senescent
      rat hearts was less than that seen in young rat hearts. Moreover, fasting
      decreased glucose utilisation in hearts from young rats, an effect which was not
      found in hearts from old rats. Furthermore, myocardial glycogen utilisation was
      increased in all groups of aged rats compared with that of young adults,
      particularly under fasting conditions. It is concluded that fasting is less
      detrimental to the aged myocardium during low-flow ischemia than to the young
      myocardium because it does not further reduce exogenous glucose utilisation, and
      it stimulates glycogen consumption. Moreover, a reduction in exogenous glucose
      utilisation, which is only partly compensated for by increased glycogenolytic
      flux could be, at least in part, responsible for the increased ischemic
      contracture in hearts from old fed rats. Finally, our glucose-free experiments
      suggest that residual oxidative phosphorylation during low-flow ischemia might be
      less relevant in hearts from senescent rats than in those from young adults.

PMID- 10936506
TI  - Superoxide dismutase gene expression in skeletal muscle: fiber-specific effect of
      age.
AB  - The influence of ageing on the expression of two superoxide dismutase (SOD)
      isozymes was examined in three different skeletal muscle fiber types of young (Y,
      8 mo) and old (O, 25 mo) rats. Total SOD activity was increased with age in the
      gastrocnemius (Gas, type II(mix)) and superficial vastus lateralis (SVL, type
      IIb) but unchanged in the soleus (Sol, type I). The increased SOD activity in SVL
      was due to increased cytosolic SOD (CuZn SOD), whereas both mitochondrial (Mn
      SOD) and CuZn SOD activities were increased in Gas. In Sol, Mn SOD activity was
      significantly increased in aged rats. Mn SOD mRNA level was significantly
      decreased with age in all three muscles examined, while Mn SOD protein content
      was not altered. Ageing did not affect CuZn SOD mRNA abundance in any of the
      muscles, but significantly increased CuZn SOD protein content in aged Gas and
      Sol. Binding of two redox-sensitive transcription factors, nuclear factor-kappaB
      (NFkappaB) and activator protein-1 (AP-1) was significantly decreased with age in
      all three muscle types. These results indicate that increased SOD activity in
      aged skeletal muscle is not associated with higher levels of gene transcription.
      Increases in Mn SOD activity seen in aged Gas and Sol are the result of post
      translational modification of the enzyme, whereas increases in CuZn SOD activity
      during ageing may be due to both translational and post-translational control.

PMID- 10936507
TI  - Interferon beta neutralizing antibodies in multiple sclerosis: neutralizing
      activity and cross-reactivity with three different preparations.
AB  - The presence and titer of neutralizing antibodies (NABs) was evaluated by an
      antiviral biological assay in 387 samples of 111 multiple sclerosis (MS) patients
      treated with one of the three commercial preparations of interferon beta
      (IFNbeta). Fifty NAB positive samples were found in 19 patients: 11 treated with
      IFNbeta-1b (Betaferon(R)) and eight with IFNbeta-1a (five with Avonex(R) and
      three with Rebif(R)). All the 38 NABs+ samples of patients treated with IFNbeta
      1b cross-reacted with IFNbeta-1a of both commercial types. The median level of
      neutralizing units (NUs) of the sera was higher when tested against IFNbeta-1a
      than against IFNbeta-1b (p=0.000 vs. Avonexr(R) and p=0.003 vs. Rebif(R)). In
      line with these data, the NABs+ sera of patients treated with IFNbeta-1a cross
      reacted with IFNbeta-1b and the level of NUs were lower when tested against
      IFNbeta-1b than against IFNbeta-1a (p=0.003). The different amount of NUs against
      IFNbeta types 1a and 1b could be due to the presence of aggregates in the IFNbeta
      1b preparation. The different levels of cross-reactivity of NABs could reduce the
      bioavailability and therapeutic efficacy of IFNbeta in NABs+ patients switching
      from IFNbeta-1b to IFNbeta-1a.

PMID- 10936508
TI  - TGF-beta 1 differentially regulates IL-2 expression and [3H]-thymidine
      incorporation in CD3 epsilon mAb- and CD28 mAb-activated splenocytes and
      thymocytes.
AB  - Transforming growth factor-beta(1) (TGF-beta(1)) is a critical bifunctional
      regulator of inflammatory responses. Evidence strongly suggests that these
      regulatory consequences are, at least in part, a result of profound pleiotropic
      effects on T lymphocyte effector function. The mechanisms underlying the
      contradictory biological effects of TGF-beta(1) remain ambiguous. The objective
      of the present studies was to test the hypothesis that the concentration of TGF
      beta(1) and the temporal relationship between activation of the T cell receptor
      (TCR) and the TGF-beta receptor regulate the effect of TGF-beta(1) on T
      lymphocyte activation and proliferation. Toward this end, we have quantified the
      concentration- and time-dependent effect of TGF-beta(1) on interleukin-2 (IL-2)
      protein secretion as an index of T lymphocyte activation and [3H]-thymidine
      incorporation as an index of cell proliferation in primary splenocytes and
      thymocytes. Our results suggest that TGF-beta(1) stimulates IL-2 production at
      low concentrations (0.1-1 pg/ml) and conversely inhibits IL-2 production at high
      concentrations (1-10 ng/ml) in CD3epsilon monoclonal antibody (mAb)+/-CD28 mAb
      activated splenocytes. Additionally, concentrations of TGF-beta(1) that stimulate
      IL-2 production in CD3epsilon mAb+CD28 mAb-activated splenocytes concominantly
      inhibit splenocyte proliferation under similar conditions. Furthermore, we
      provide evidence suggesting that the effects of TGF-beta(1) on T lymphocytes are
      dependent upon the temporal relationship between activation of the TCR and the
      TGF-beta receptor. A time-dependent loss of a stimulatory effect and a
      concomitant gain of an inhibitory response by TGF-beta(1) on IL-2 production in
      response to CD3epsilon and CD28 mAbs is observed when TGF-beta(1) is added
      following T lymphocyte activation. In summary, these data unequivocally
      demonstrate that the orchestration of paradoxical effects of TGF-beta(1) on T
      lymphocyte function is dependent upon the concentration of TGF-beta(1) and the
      temporal relationship between activation of signaling through the TCR and the TGF
      beta receptor. Future mechanistic studies addressing the putative role that these
      factors play in modulating the effects of TGF-beta(1) on T lymphocyte activity
      will undoubtedly provide valuable insight towards the pharmacological
      intervention of inflammatory responses.

PMID- 10936509
TI  - Endotoxin and muramyl dipeptide modulate surface receptor expression on human
      mononuclear cells.
AB  - Endotoxin (lipopolysaccharide (LPS), 100 ng/ml) and muramyl dipeptide (MDP 100
      ng/ml), two immunomodulatory bacterial cell wall products, were incubated with
      human whole blood, and the expression of receptors involved in antigen
      presentation, costimulation, and cell activation was investigated by use of flow
      cytometry. On monocytes, LPS and MDP increased surface expression of human
      leukocyte antigen-DR (HLA-DR), CD18, CD54 (intercellular adhesion molecule-1,
      ICAM-1), and CD86 (B7-2). On lymphocytes, LPS but not MDP increased HLA-DR
      expression after 18 h. The expression of CD28, CD49d/CD29, and CD106 (vascular
      cell adhesion molecule-1, VCAM-1) remained unchanged on both monocytes and
      lymphocytes. The early increase (1-6 h) of CD18 and ICAM-1 expression led us to
      hypothesize that CD18-dependent costimulatory signals were involved in the later
      (6 h) increase of monocyte HLA-DR expression. However, blocking studies using
      monoclonal antibodies against CD18 (IB4, 15 microg/ml) demonstrated that the LPS-
      and MDP-induced increase of HLA-DR and ICAM-1 expression on monocytes was not
      mediated through CD18. LPS induced the expression of the early activation marker
      CD69 by a CD14-dependent but CD18-independent mechanism, whereas MDP did not
      induce CD69 expression. Analysis of leukocyte subsets demonstrated that CD4(+) T
      cells, CD8(+) T-cell, CD19(+) B-cells, CD56(+) natural killer (NK)-cells, and
      CD14(+) monocytes increased the expression of CD69 after stimulation with LPS.
      Collectively, these data demonstrate a stronger immunomodulatory effect of LPS
      compared with MDP which may, in part, explain the established difference of
      toxicity between these two bacterial cell wall products.

PMID- 10936510
TI  - Santonin-related compound 2 inhibits the expression of ICAM-1 in response to IL-1
      stimulation by blocking the signaling pathway upstream of I kappa B degradation.
AB  - Santonin-related compounds (SRCs) were synthesized from the starting material L
      alpha-santonin and tested for the biological activity on the expression of
      intercellular adhesion molecule-1 (ICAM-1) in response to IL-1 stimulation on
      human adenocarcinoma cells. One of the bromoketone derivatives termed SRC2 [11S-2
      alpha-bromo-3-oxoeudesmanno-13,6 alpha-lactone] strongly inhibited the ICAM-1
      expression at an IC(50) value of 5.9 microM, whereas L-alpha-santonin itself was
      totally inactive up to 100 microM. The blockage of ICAM-1 expression by SRC2 was
      not due to the direct inhibition of de novo RNA and protein synthesis. The
      nuclear translocation of NF-kappaB subunit p65 was markedly prevented by SRC2.
      Moreover, I kappa B alpha degradation upon IL-1 stimulation was strongly
      inhibited by SRC2. These observations suggest that SRC2 blocks the IL-1 signaling
      pathway upstream of I kappa B degradation.

PMID- 10936511
TI  - Polyglutamation of antifolates is not required for induction of extracellular
      release of adenosine or expression of their anti-inflammatory effects.
AB  - Methotrexate (MTX) exerts an anti-inflammatory effect, reportedly by enhancing
      the release of adenosine, through an accumulation of 5-amino-4
      imidazolecarboxamide ribonucleotide (AICAR). To examine the role of
      polyglutamation in promoting anti-inflammatory effects by antifolates, we tested
      whether a new antifolate designed to be resistant to intracellular
      polyglutamation (MX-68) exhibited anti-inflammatory effects and stimulated
      adenosine release. Both MX-68 and MTX (at concentrations greater than 0.1 microM)
      increased the release of adenosine from Daudi cells in vitro. Inhibition of AICAR
      synthesis suppressed adenosine release by MX-68 and MTX. The anti-inflammatory
      effects of antifolates were estimated using the murine air pouch model, in which
      a BALB/c mouse was intraperitoneally injected with MX-68 or MTX once a week for 3
      weeks. MX-68 (0.5 mg kg(-1) week(-1)), as well as MTX, inhibited infiltration of
      leukocytes into the air pouch. This inhibitory effect was suppressed in the
      presence of an adenosine A(2) receptor antagonist, 3,7-dimethyl-1
      propargylxanthine (DMPX). These results suggest that MX-68, like MTX, exerts anti
      inflammatory effects through the accumulation of AICAR and release of adenosine.
      These results suggest that polyglutamation of antifolate is not required for
      expression of anti-inflammatory effects.

PMID- 10936512
TI  - Differential effects of buprenorphine and morphine on immune and neuroendocrine
      functions following acute administration in the rat mesencephalon periaqueductal
      gray.
AB  - The effects of the mu-opioid receptor agonists buprenorphine and morphine on
      immune and neuroendocrine functions through acute action in the rat mesencephalon
      periaqueductal gray (PAG) were evaluated. Buprenorphine is an analgesic recently
      approved for the treatment of drug dependency. In this study, it was shown that
      injection of an equianalgesic dose of buprenorphine (related to morphine) into
      the ventral-caudal PAG did not alter splenic NK cell, T cell, and macrophage
      functions, whereas morphine significantly (p<0.001) suppressed splenic NK cell
      cytotoxic activity (14-50% reduction), splenic and thymic T cell proliferation to
      concanavalin A (Con A, 43-76% reduction), antiTCR (T cell receptor) (85%
      reduction) and IL-2 (36-48% reduction), and macrophage functions including nitric
      oxide (36-41% reduction) and TNF-alpha production (26%), and phagocytosis of
      Candida albicans (39%). In addition, buprenorphine was associated with
      significant (p<0.0001) reductions in adrenocorticotropic hormone (ACTH) and
      corticosterone (CSO) plasma levels, without altering norepinephrine (NE) and
      serotonin splenic dialysate levels. In contrast, morphine significantly
      (p<0.0001) increased glucocorticoid and catecholamine levels in plasma and spleen
      dialysates, respectively. These results indicated that buprenorphine did not
      activate either the hypothalamic-pituitary-adrenal (HPA) axis with glucocorticoid
      release, or the sympathetic nerve (SNS) activity with bioamine production, and
      was not associated with immunosuppression. The lack of effects of buprenorphine
      on neuroendocrine systems may be related to its partial agonist properties, the
      absence of effects on immune system function, and may be associated with the
      reduction in craving observed in addictive disorders.

PMID- 10936513
TI  - Distribution of leukotriene B4 receptors in human hematopoietic cells.
AB  - Leukotriene B4 (LTB4), a product of arachidonic acid metabolism, plays an
      important role in inflammatory responses. We have cloned from human
      erythroleukemia cells, a G protein-coupled receptor, designated P2Y(7), which was
      later identified as the receptor for LTB4 (B-LTR). We have investigated the
      distribution of LTB4 receptors in various hematopoietic cells. Northern blotting
      and reverse transcription-coupled polymerase chain reaction (RT-PCR) analyses
      using radiolabeled LTB4 receptor cDNA as a probe indicated the presence of LTB4
      receptor mRNA in peripheral blood leukocytes but not in platelets. Flow cytometry
      analysis of peripheral blood cells using specific LTB4 receptor antibodies
      revealed that monocytes, granulocytes, and lymphocytes, but not platelets,
      express LTB4 receptors. RT-PCR-Southern hybridization analysis revealed that
      peripheral blood leukocytes and human umbilical vein endothelial cells express
      the LTB4 receptor. Of the hematopoietic cell lines tested, promonocytic U937
      cells, promyelocytic HL-60 cells, K562 cells, and human erythroleukemia cells
      express the LTB4 receptor. These results suggest a physiological role for the
      LTB4 receptor in the stimulation of monocytes, neutrophils, and endothelial
      cells.

PMID- 10936514
TI  - Hydrogen peroxide inhibits the immune response to lipopolysaccharide by
      attenuating signaling through c-Jun N-terminal kinase and p38 associated with
      protein kinase C.
AB  - This study examined the immunomodulatory effects of hydrogen peroxide (H(2)O(2))
      in B6C3F1 mouse splenic lymphocytes. H(2)O(2) produced a marked and dose-related
      inhibition of both lipopolysaccharide (LPS)-induced B-cell proliferation and
      concanavalin A (Con A)-induced T-cell proliferation. Unexpectedly, little effect
      was observed with H(2)O(2) on the antibody-forming cell (AFC) response to the
      polyclonal B-cell activator, LPS. It was also observed that H(2)O(2) did not have
      any detectable effect on forskolin-stimulated adenylate cyclase, indicating that
      cyclic AMP (cAMP) is not a mediator of H(2)O(2)-induced suppression of the immune
      response. Rather, LPS-induced activation of protein kinase C (PKC) was completely
      inhibited when cells were pretreated with H(2)O(2) for 18 h, although PKC
      activity was increased approximately twofold following treatment with H(2)O(2)
      for 10 min. In addition, H(2)O(2) pretreatment blocked the phosphorylation of two
      stress-activated mitogen-activated protein kinases (MAPKs), c-Jun N-terminal
      kinase (JNK) and p38 by LPS in a concentration-dependent fashion. Therefore,
      these data suggest that H(2)O(2) suppresses immune response through the
      desensitization of PKC, which subsequently results in inhibition of JNK and p38.

PMID- 10936515
TI  - Dexamethasone inhibits IL-1 beta gene expression in LPS-stimulated RAW 264.7
      cells by blocking NF-kappa B/Rel and AP-1 activation.
AB  - In the present study, the mechanism by which dexamethasone (DEX) inhibited IL
      1beta gene expression in bacterial lipopolysaccharide (LPS)-activated RAW 264.7
      cells was investigated. The decrease in LPS-induced IL-1beta mRNA expression was
      demonstrated by quantitative reverse transcription polymerase chain reaction (RT
      PCR). Since the promoter in IL-1beta gene contains binding motifs for NF
      kappaB/Rel, AP-1, NF-IL6, and CREB/ATF, which appear to be important in LPS
      mediated IL-1beta induction, the effects of DEX on the activation of these
      transcription factors were examined. Treatment of DEX to RAW 264.7 cells induced
      a dose-related inhibition of NF-kappaB/Rel and AP-1 in chloramphenicol
      acetyltransferase activity, while neither NF-IL6 nor CREB/ATF activation was
      affected by DEX. Treatment of RAW 264.7 cells with DEX inhibited DNA binding of
      NF-kappaB/Rel and AP-1 proteins to their cognate DNA sites as measured by
      electrophoretic mobility shift assay (EMSA). DEX treatment caused a significant
      reduction in nuclear c-rel, p65, and p50 protein contents, and these decreases
      were paralleled by the accumulation of cytoplasmic c-rel, p65, and p50. DEX
      treatment of RAW 264.7 cells did not inhibit the nuclear translocation of c-jun
      and c-fos. We found that the inhibition of IL-1beta production by DEX is not
      related to p38, which is important in the IL-1beta induction. These results
      suggest that DEX may inhibit IL-1beta gene expression by a mechanism involving
      the blocking of LPS-induced NF-kappaB/Rel and AP-1 activation.

PMID- 10936517
TI  - C3 activation is inhibited by analogs of compstatin but not by serine protease
      inhibitors or peptidyl alpha-ketoheterocycles.
AB  - C3 convertase is a key enzyme in the complement cascade and is an attractive
      therapeutic target for drug design. Recent studies have demonstrated that this
      enzyme is inhibited by compstatin (Morikis, D. , Assa-Munt, N., Sahu, A.,
      Lambris, J.D., 1998. Solution structure of Compstatin, a potent complement
      inhibitor. Protein Sci. (7) 619-627; Sahu, A., Kay, B.K., Lambris, J.D., 1996.
      Inhibition of human complement by a C3-binding peptide isolated from a phage
      displayed random peptide library. J. Immunol. (157) 884-891), a 13 amino acid
      cyclic peptide that binds to C3. Since the enzyme exhibits some homology to
      serine proteases, substrate-based design could be another avenue for drug design.
      In this study, we confirm the activity of compstatin using different sources of
      enzyme and different assay systems. We also tested the activity of substituted
      compstatin analogs and compared the selectivity and toxicity of these compounds
      to peptidyl alpha-ketoheterocyclic compounds. Our work confirms the activity of
      compstatin in both alternative and classical complement pathways, describes 11
      new active analogs of this cyclic peptide, and provides evidence for key segments
      of the peptide for activity. Compstatin and related active analogs showed little
      or no inhibition of clotting or key enzymes in the clotting cascade nor did they
      appear to have significant cytotoxicity. The characteristics of compstatin
      suggest that this peptide and its analogs could be attractive candidates for
      further clinical development. By contrast, known serine protease inhibitors,
      including peptidyl alpha-ketoheterocycles, did not inhibit C3 convertase
      illustrating the atypical nature of this enzyme.

PMID- 10936518
TI  - Micropropagation of Dev-ringal
AB  - An efficient protocol for in vitro propagation of Thamnocalamus spathiflorus
      (Trin.) Munro, an evergreen temperate bamboo, through multiple shoot formation
      from zygotic embryos excised from germinating seeds, as well as from nodal
      explants taken from a 2-year-old plant has been developed. Multiple shoot
      formation was standardized in both the cases on Murashige and Skoog (MS) medium
      supplemented with 5.0 uM 6-benzylaminopurine (BAP) and 1.0 uM indole-3-butyric
      acid (IBA). Clumps of three to four microshoots when transferred to plant growth
      regulator-free medium following 14 days' initial culture on medium supplemented
      with 150.0 uM IBA, resulted in 100% rooting with five to 12 roots per rooted
      plant. Then, 18 months following the transfer of in vitro propagated plants into
      earthen pots containing soil and growth under outdoor conditions, gas and water
      vapour exchange rates were measured at different light levels (0, 100, 500, 1000,
      1500, 2000 umol(-2) s(-1)), and compared with seedlings of the same age. Light
      optima for photosynthesis were recorded approximately 1000 umol m(-2) s(-1) in in
      vitro propagated plants as well as seedlings. Water use efficiency increased with
      increase in the light intensity up to 1000 umol m(-2) s(-1) and then decreased
      subsequently at higher light intensities. Stomatal conductance and transpiration
      also increased with the increase in light intensity up to 2000 umol(-2) s(-1).
      Intercellular CO(2) concentration (C(i)) and the ratio of intercellular CO(2)
      concentration to ambient CO(2) (C(i)/C(a)) decreased with the increase in light
      intensity up to 500 umol(-2) s(-1) and then reached nearly constant levels at
      higher light intensities. The results show that in vitro propagated and hardened
      plants of T. spathiflorus are morphologically as well as functionally comparable
      to seed raised plants of the same age, within the limits of this study.

PMID- 10936516
TI  - Effect of poloxamer CRL-1072 on drug uptake and nitric-oxide-mediated killing of
      Mycobacterium avium by macrophages.
AB  - Mycobacterium avium-intracellulare complex (MAI) are common pathogens of
      opportunistic infections that are naturally resistant to most antibiotics and
      develop acquired resistance rapidly. An experimental drug, poloxamer CRL-1072,
      was found to have two unusual properties: it synergistically enhanced the
      activity of several antibiotics against MAI even though it had little activity as
      a single agent and it had greater activity against MAI in macrophage culture or
      in mice than in broth culture. Studies were undertaken to investigate the
      mechanisms of these effects. CRL-1072 was taken up by MAI and enhanced the uptake
      of fluorescent-labeled streptomycin and erythromycin in broth culture. The
      labeled antibiotics had reduced activity so the relevance for naive antibiotics
      must be inferred. In culture with human U937 monocytoid cells, CRL-1072 became
      localized in phagosomes and promoted uptake of streptomycin. Finally, CRL-1072
      was found to induce production of mRNA for inducible nitric oxide synthase (iNOS)
      and nitric oxide (NO) by U937 cells. The antimycobacterial effect in macrophages
      was reversed by the iNOS inhibitor N-monomethyl L-arginine (NMMA), suggesting
      that CRL-1072 promotes killing of MAI by inducing NO. These effects were induced
      by noncytotoxic concentrations of CRL-1072. These data suggest that the
      antimycobacterial mechanisms of CRL-1072 include enhancing the delivery of
      antibiotic to targets within MAI and enhancement of the ability of macrophages to
      kill ingested organisms.

PMID- 10936519
TI  - Delayed activation of post-transcriptional gene silencing and de novo transgene
      methylation in plants with the coat protein gene of sweet potato feathery mottle
      potyvirus.
AB  - The relationship between post-transcriptional gene silencing (PTGS) and DNA
      methylation was examined using Nicotiana benthamiana transformed with the coat
      protein gene including the 3' non-translated region of sweet potato feathery
      mottle potyvirus. Line 4.28 showed a delayed activation of the transgene
      silencing in comparison with the other silenced lines, and showed complete
      resistance against the recombinant potato virus X engineered to contain the
      sequence homologous to the transgene when the silencing was activated. The
      transgene methylation in line 4.28 was less extensive in comparison with those of
      the other silenced lines before the silencing was activated. However, the extent
      of methylation increased in the course of plant development and became comparable
      with those in the other silenced lines. The activated silencing and the increased
      transgene methylation were reset after meiosis. However, the characters of
      delayed activation of the silencing and developmentally increased transgene
      methylation were meiotically transmitted to the next generation. These results
      suggest that transgene(s) itself has a potential to trigger and reset DNA
      methylation, which could determine a state of PTGS.

PMID- 10936520
TI  - Water requirements of terrestrial and epiphytic orchid seeds and seedlings, and
      evidence for water uptake by means of mycotrophy.
AB  - The use of endomycorrhizal fungi as an energy source (=mycotrophy) initiates
      seedling development and supplements or replaces photosynthesis in all orchids in
      nature. Fungus-infected and non-infected seeds of the monkey face orchid,
      Platanthera integrilabia, a US Federally-threatened terrestrial species, had a
      different set of water relations than seeds of the green fly orchid, Epidendrum
      conopseum, a subtropical epiphyte. Seeds of the terrestrial species had lower
      water loss rates, smaller activation energies for water loss and absorbed water
      from lower relative humidities. Thus, the epiphyte lacks the enhanced water
      retention capacity associated with the terrestrial species, implying that
      epiphytic orchids are capable of germinating quickly given an adequately moist
      substrate. After germination, water content of fungus-infected seeds was higher.
      These results provide first time fundamental information related to habitat
      preference by analyzing seed. Germination is considerably enhanced with
      mycorrhizal fungi that facilitate the absorption of free water by their orchid
      seed hosts.

PMID- 10936521
TI  - Fermentative metabolism in grape berries: isolation and characterization of
      pyruvate decarboxylase cDNA and analysis of its expression throughout berry
      development.
AB  - The involvement of pyruvate decarboxylase (PDC) in the control of alcohol
      production during ripening of fruit tissues under aerobic conditions has been
      only partially studied. Enzymological studies showed a significant increase in
      PDC activity during the ripening of oranges and pears, concurrently with the
      induction of ethanol production. In tomato, on the other hand, the induction of
      ethanol production and ADH gene expression after the onset of ripening was not
      accompanied by induction of PDC activity. The isolation of PDC cDNA from fruits
      has not yet been reported, nor has its expression pattern during fruit
      development. We report here the isolation of a cDNA clone encoding for a grape
      PDC and the characterization of its expression throughout berry development. The
      pattern of PDC gene expression throughout berry development, combined with
      earlier findings on constitutive PDC activity in the berry, may suggest that PDC
      is not the limiting factor for the production of ethanol in the berry, which is
      induced only after the onset of berry ripening. Alternatively, the induction of
      ADH gene expression, which occurs only after the onset of ripening in both
      tomatoes and grape berries, may serve as a regulator of ethanol production in
      response to a ripening-related cue.

PMID- 10936522
TI  - Histological analysis of indirect somatic embryogenesis in the Marsh clubmoss
      Lycopodiella inundata (L.) Holub (Pteridophytes).
AB  - An efficient in vitro plant regeneration method was developed for Lycopodiella
      inundata (L.) Holub, an endangered medicinal Lycopod (Pteridophytes). Vegetative
      apices were used as explant material. Nodular calluses were established after
      three cycles (13 weeks each) on a medium containing a few minerals and organic
      compounds and supplemented with 0.05 uM 3-indolebutyric acid (IBA) and 1.4 uM
      kinetin (Kin). Propagation was achieved every 13 weeks on this callus medium
      (CM). When nodular calluses were transferred on a medium supplemented with 2.5 uM
      IBA and 0.33 uM gibberellic acid (GA(3)) designated as embryogenic medium (EM),
      organized structures appeared and developed into plantlets. Development phases
      were characterized by histological studies. Some phases of zygotic embryogenesis
      previously described for Lycopods were observed in L. inundata. Histological
      analyses established that an indirect somatic embryo was derived from a single
      embryogenic cell by following the zygotic developmental pathway. As this
      phenomenon has not previously been reported in Lycopods, a comparison between
      somatic and zygotic embryos is discussed based upon morphology and histology.

PMID- 10936523
TI  - Improved plant regeneration from cultured leaf segments in peanut (Arachis
      hypogaea L.) by limited exposure to thidiazuron.
AB  - Bud primordia were induced from leaf segments, which were harvested from young
      seedlings of Spanish type peanut (Arachis hypogaea L. cv. Chico), on 0.8% agar
      solidified medium containing Murashige and Skoog (MS) basal salts supplemented
      with B5 vitamins, 1 mg/l NAA and various cytokinins such as benzyladenine (BA),
      isopentenyladenine (2ip), kinetin (KIN), chloropyridylphenylurea (4PU),
      thidiazuron (TDZ), zeatin (ZTN) in different concentrations. Among the cytokinins
      tested, TDZ was found to be the most efficient for inducing bud primordia.
      However, continuous culture on TDZ-containing media induced abnormal development
      of these primordia, and they failed to grow into plantlets. Histological
      observations revealed that the malformation most often obtained was a shoot-like
      structure which lacked shoot apical meristem (SAM) and had disorganized vascular
      bundles. For normal shoot regeneration, it was necessary to limit the culture
      period of the explants on TDZ-containing medium to 7 days at 10 mg/l or 21 days
      at 1 mg/l and then transfer them onto plant growth regulator-free medium. The
      percentage of conversion from shoot buds to shoots was 34.7%. When shoots were
      removed from the explants and transferred onto basal medium containing 1 mg/l
      NAA, all regenerated shoots readily rooted and successfully acclimatized. All of
      the acclimatized plants produced viable seeds in the greenhouse condition.

PMID- 10936524
TI  - Fertile pea plants regenerate from protoplasts when calluses have not undergone
      endoreduplication.
AB  - Large numbers of viable protoplasts were isolated and cultured from five pea
      genotypes. Calluses obtained (percent final plating efficiency (% FPE)=0.65-2.82%
      of initially plated protoplasts) exhibited great differences in proliferation and
      regeneration competence between and within genotypes. Flow cytometric analyses
      showed the occurrence of endoreduplication processes correlated with such
      differences, and could serve as a tool for the early prediction of plant
      regeneration competence from protoplasts. Fertile plants were produced only from
      calluses with a normal DNA level.

PMID- 10936525
TI  - Comparison of the phytotoxic activity of the phytotoxin destruxin B and four
      natural analogs.
AB  - A quantitative bioassay utilizing staining of plant cell suspension cultures of
      Sinapis alba was employed to establish a structure-phytotoxic activity
      correlation among destruxin B, homodestruxin B, and desmethyldestruxin B, toxins
      produced by Alternaria brassicae (Berk.) Sacc., the causative agent of Alternaria
      blackspot of brassicas. In addition, the phytotoxicity of destruxin B,
      homodestruxin B, and their respective metabolites hydroxydestruxin B and
      hydroxyhomodestruxin B were tested on resistant and susceptible plant species
      utilizing in planta leaf assays and leaf uptake of toxin solutions. Overall, the
      results obtained from punctured leaf and cell staining assays indicated that
      homodestruxin B (EC(50) 3x10(-4) M) was the most toxic of the five compounds,
      followed by destruxin B (EC(50) 5x10(-4) M), and desmethyldestruxin B
      (EC(50)&z.Gt;5x10(-4) M). On the other hand, the hydroxylated destruxins
      (hydroxydestruxin B EC(50)&z.Gt;5x10(-4) M) were significantly less phytotoxic
      than the parent toxins.

PMID- 10936526
TI  - Nicotiana glauca: another plant species containing vitamin D(3) metabolites.
AB  - Vitamin D(3)-related compounds have been detected in various plant species,
      mostly belonging to the Solanaceae. In this work we show that Nicotiana glauca, a
      widespread member of this taxonomic family, contains 7-dehydrocholesterol,
      vitamin D(3) and hydroxylated derivatives bearing precursor-product metabolic
      relationships in vertebrates. Leaves collected in the field and callus cultures
      were used. By means of specific radioreceptor binding assays and mass
      spectrometry of purified fractions obtained from plant tissue lipid extracts by
      Sephadex LH-20 and Sep-Pak C18 chromatography followed by HPLC, we established
      the presence of 7-dehydrocholesterol, vitamin D(3), 25(OH)-vitamin D(3) and
      1alpha,25(OH)(2)-vitamin D(3) (1alpha,25(OH)(2)D(3)), the latter being a
      hormonally relevant metabolite in animals. These results indicate that N. glauca
      may represent a useful species in which to characterize the biosynthetic pathway
      and physiological functions of vitamin D(3) compounds in plants. In addition,
      tissue culture of N. glauca could become a significant tool for biotechnological
      production of 1alpha,25(OH)(2)D(3).

PMID- 10936527
TI  - Structure, expression and promoter activity of two polyubiquitin genes from rice
      (Oryza sativa L.).
AB  - We have isolated two rice polyubiquitin genes designated as RUBQ1 and RUBQ2 by
      screening a Bacterial Artificial Chromosome (BAC) genomic library with a 32P
      labeled ubiquitin cDNA probe. DNA sequence data revealed that both genes
      contained an open reading frame encoding a hexameric precursor ubiquitin and an
      intron immediate upstream of the initiation codon. The deduced amino acid
      sequences of both genes were identical to each other and to other plant ubiquitin
      sequences. Several putative regulatory elements such as enhancer core and heat
      shock consensus sequences were found in the 5'-upstream regions of both genes.
      Northern blot analyses using the 3'-untranslated region as gene specific probes
      showed that both genes were actively expressed in all rice plant tissues tested.
      Differential expression was observed in roots where RUBQ2 appeared to be
      predominantly expressed. Chimeric genes containing the 5'-upstream region
      including the intron of RUBQ1 or RUBQ2 and the beta-glucuronidase (GUS) coding
      region were constructed and transferred into rice suspension cells via particle
      bombardment. GUS activity from constructs containing RUBQ1 and RUBQ2 promoters in
      rice suspension cells was ten to 15-fold greater than those using the Cauliflower
      Mosaic Virus 35S (CaMV 35S) promoter, and two to threefold greater than
      constructs with the maize polyubiquitin Ubi1 promoter. The results demonstrate
      the potential usefulness of the two rice polyubiquitin promoters in rice or other
      monocot transformation systems.

PMID- 10936528
TI  - Polysomaty analysis in diploid and tetraploid Portulaca grandiflora.
AB  - Polysomaty analysis of the succulent portulaca (Portulaca grandiflora Hook.)
      plant was carried out using flow cytometry. For both diploid and tetraploid
      plants, mature leaf tissue was found to have a higher level of polysomaty than
      young leaf tissue. Mesophyll (MP), bundle sheath (BSP) and water storage
      protoplasts (WSP) were isolated from leaf tissues of diploid portulaca plants.
      WSP had a higher degree of endopolyploidization than MP and BSP. The ploidy
      distribution was also variable in different floral organs. Tetraploid plants
      artificially induced by colchicine treatment showed a decline in the degree of
      polysomaty compared to diploid plants. Tetraploid plants had more spherical
      leaves, a larger number of petals and lower pollen fertility than diploid plants.

PMID- 10936529
TI  - Improvement of in vitro gynogenesis induction in onion (Allium cepa L.) using
      polyamines.
AB  - The effects of polyamines on gynogenetic embryogenesis and regeneration of
      plantlets in onion were studied. Whole flowers from two onion genotypes,
      'Valcatorce INTA' cultivar and 'Torrentina' population, were used as initial
      explants. Embryo induction was greatest with a combined treatment of 2 mM
      putrescine and 0.1 mM spermidine. Addition of putrescine alone, with a few
      exceptions, did not have any significant effect on either embryo induction or
      haploid plantlet production for both onion genotypes. 'Torrentina' showed a
      higher embryo generation capacity (9.5%) than 'Valcatorce INTA' (2.8%). Fast
      regeneration of embryos was achieved (from 60 to 90 days) as compared to a
      previously reported time of 46-152 days. The use of spermidine (0.1 mM) after 15
      days of culture promoted further embryo maturation and plantlet formation.
      'Torrentina' produced more haploid plants (1.90%). This is the first report of
      successful use of polyamines for induction of gynogenic embryos and regeneration
      of onion plantlets.

PMID- 10936530
TI  - Production of fertile transgenic wheat plants via tissue electroporation.
AB  - Electroporation has been used effectively to deliver DNA into the tissue of
      intact wheat immature embryos. Transformed plantlets have been recovered after
      electroporation using field strengths of 275 and 750 V/cm, 960-uF capacitor and
      50 ug/ml of linear plasmid DNA, containing bar and uidA genes. The field strength
      of 750 V/cm proved to be more effective for DNA delivery (estimated by transient
      GUS expression) and for recovery of transformed plants (two transgenic plants
      were recovered with an efficiency of 0.4%). After application of a field strength
      of 275 V/cm there was no visual evidence of transient GUS expression, but one
      transgenic plant was recovered with an efficiency of 0.2%, based on the number of
      electroporated embryos. This indicates that the amount of DNA delivered into the
      cells was too low for visual identification of transient GUS expression and that
      GUS expression may not provide an appropriate assessment of the efficiency of DNA
      delivery. Southern blot hybridisation has revealed a low copy number of transgene
      integration with some rearrangements in integrated loci. None of the transgenic
      plants has shown any visual GUS expression, although we could amplify the
      transcript of the uidA gene in T(0) progeny using RT-PCR. This may indicate that
      suppression of uidA expression occurred at the post-transcriptional level. The
      efficiency of tissue electroporation is still dependent on the quality of the
      plant material which is used but the transformation events were reproducible from
      one group of experiments to another. At present, this technique is dependent on a
      combination of factors including pretreatments of the recipient tissue, quality
      of tissue culture and optimisation of electroporation conditions.

PMID- 10936531
TI  - Analysis of transgenic grapevine (Vitis rupestris) and Nicotiana benthamiana
      plants expressing an Arabis mosaic virus coat protein gene.
AB  - A disarmed LBA4404 strain of Agrobacterium tumefaciens harboring a binary vector
      which contained chimeric genes encoding the neomycin phosphotransferase (npt II)
      and the coat protein (CP) of Arabis mosaic nepovirus (ArMV) was used in co
      cultivation experiments with leaf discs of Nicotiana benthamiana and somatic
      embryos of the grapevine rootstock cultivar Vitis rupestris. Transgenic N.
      benthamiana expressing the ArMV CP gene were regenerated and six independent
      lines were characterized. Enzyme-linked immunosorbent assay (ELISA) performed on
      leaf tissue demonstrated the accumulation of the ArMV CP in five of the six lines
      analyzed. Immunosorbent electron microscopy (ISEM) studies revealed the presence
      of virion-like isometric particles (VLPs) reacting to a rabbit antiserum specific
      to ArMV virions. ArMV-CP expressing transgenic N. benthamiana lines showed
      protection against ArMV expressed as a delay in infection and a reduction of the
      percentage of infected plants. Four independent transgenic lines of V. rupestris
      transformed with the ArMV CP gene were regenerated and characterized. In contrast
      to N. benthamiana, transgenic V. rupestris did not accumulate the ArMV CP at
      levels detectable by ELISA and no VLPs could be observed by ISEM. Northern blot
      analysis showed that the ArMV CP mRNA was expressed at lower level in V.
      rupestris compared with N. benthamiana. The reason for this difference in
      transgene expression and/or mRNA stability between grapevine and N. benthamiana
      is unclear, but the genetic state of the transgene(s) (homozygous in N.
      benthamiana versus hemizygous in V. rupestris) may have an effect on gene
      expression.

PMID- 10936532
TI  - Water stress preconditioning to improve drought resistance in young apricot
      plants.
AB  - The effect of water stress preconditioning was studied in 1-year-old apricot
      plants (Prunus armeniaca L., cv. Bulida). Plants were submitted to different
      treatments, T-0 (control treatment) and T-1, drip irrigated daily; T-2 and T-3,
      irrigated daily at 50% and 25% of T-0, respectively; T-4 and T-5, irrigated to
      field capacity every 3 and 6 days, respectively. After 30 days, irrigation was
      withheld for 10 days, maintaining the T-0 treatment irrigated daily. After this
      period, the plants were re-irrigated to run-off and treated as control treatment.
      The stomatal closure and epinasty observed in response to water stress
      represented adaptive mechanisms to drought, allowing the plants to regulate water
      loss more effectively and prevent leaf heating. A substantial reduction in the
      irrigation water supplied combined with a high frequency of application (T-3
      treatment) promoted plant hardening; the plants enduring drought better, due to
      their greater osmotic adjustment (0.77 MPa), which prevented severe plant
      dehydration and leaf abscission. Such a preconditioning treatment may be valuable
      for young apricot plants in the nursery stage in order to improve their
      subsequent resistance to drought. A 50% reduction in daily irrigation (T-2
      treatment) did not significantly affect either gas exchange rates or leaf turgor,
      which suggests that water should be applied frequently if deficit irrigation is
      to be implemented.

PMID- 10936533
TI  - Field studies of the leachability of aged brown coal ash.
AB  - The environmental management of ash produced from the brown coal power stations
      of the Latrobe Valley region of Australia has been studied. Current practice
      consists of slurrying fly and bottom ash, a short distance to an ash disposal
      pond. However, storage facilities are approaching capacity and alternative ash
      management strategies are required in the near future. Initially, the ash
      produced within the power stations is known to possess a large soluble mass,
      which can leach rapidly to generate a saline leachate with minor trace metal
      content. After slurrying and deposition within the ash pond, it has been
      demonstrated that the soluble mass is significantly lower and the ash can be
      considered as aged or "leached" ash - a more benign waste that meets the criteria
      for fill material. In order to assess the long-term behaviour of the leached ash
      and its suitability for co-disposal in engineered sites within overburden dumps,
      two field cells were constructed and monitored over a period of 1 year. Each cell
      was 5 x 5 m in area, 3-m deep and HDPE lined with a coarse drainage layer and
      leachate collection pipe. The first cell only collected natural rainfall and was
      known as the Dry Cell. The second cell had an external tank of 5000 l installed
      (200-mm rainfall equivalent) and water was spray-irrigated regularly to simulate
      higher rainfall and accelerate the leaching process. The cumulative inflow and
      outflow for each cell has been calculated using a linear relationship and the
      leachate quality was monitored over time. The results demonstrate that the ash
      behaves as an unsaturated porous material, with the effect of evaporation through
      the profile being dominant and controlling the production of leachate. The
      leachate quality was initially moderately saline in both cells, with the
      concentration dropping by nearly 95% in the Wet Cell by the end of the field
      study. The leachate chemistry has been analysed using the PHREEQC geochemical
      model. The log activity plots of various species suggest the mineralogical
      controls on these species in leachate. The full results from this study are
      presented.

PMID- 10936534
TI  - Liners for waste containment constructed with class F and C fly ashes.
AB  - Hydraulic conductivity of a Class F fly ash containing residual organic carbon
      was evaluated in this study using laboratory and field tests. Compacted specimens
      of the Class F fly ash mixed with various materials (sand, Class C fly ash, and
      bottom ash) were prepared in the laboratory at various water contents and
      different compactive efforts. Hydraulic conductivity of the compacted specimens
      was measured using flexible-wall permeameters. A test pad was constructed to
      determine whether a low hydraulic conductivity liner could be constructed with
      Class F fly ash mixtures. Sealed double-ring infiltrometers and two-stage
      borehole permeameters were used to measure the field hydraulic conductivity of
      the test pad. Specimens were also removed from the test pad for hydraulic
      conductivity testing in the laboratory. Results of the study showed that mixtures
      of Class F and Class C fly ashes along with coarse aggregate can be compacted to
      hydraulic conductivities needed for landfill liners provided compaction is wet of
      optimum water content. The field tests showed that constructing a fly ash liner
      with hydraulic conductivities similar to those found in the laboratory is
      challenging, and requires careful attention to factors that result in cracks and
      permeable interlift regions that result in high field hydraulic conductivity.
      Leachate collected from the base of the test pad also showed that metal leaching
      must be considered when designing a liner with fly ash.

PMID- 10936535
TI  - Phosphate immobilization using an acidic type F fly ash.
AB  - Batch equilibration experiments using a low calcium ( approximately 1 wt.% as
      CaO), acidic (pH approximately 4.5) Type F fly ash demonstrated phosphate
      immobilization on the order of 100% to 75% for 50 and 100 mg P/l solutions,
      respectively. A loosely compacted column of fly ash similarly removed 10 mg P/l
      for over 85 pore volumes. While the interactions between phosphate and calcium
      rich (Type C) ashes are relatively well understood, insight into the mechanisms
      of phosphate immobilization in Type F ash necessitated a review of the phosphate
      chemistry and interactions with acidic geomedia. Phosphate adsorption was
      subsequently modeled using a constant capacitance model approach (CCM) excluding
      precipitation reactions. Our CCM predictions of total phosphate immobilization
      (20%) were substantially less than the results of the batch equilibration
      experiments and phosphate adsorption predicted by other researchers examining
      near pure natural and synthetic geomedia due to the compositional heterogeneity
      of the fly ash. Nevertheless, for the amorphous and crystalline phases studied,
      the immobilization of phosphate in the Type F fly ash is attributed to the
      formation of insoluble aluminum and iron phosphates at low to medium values of
      pH.

PMID- 10936536
TI  - Removal of chlorophenols from aqueous solution by fly ash.
AB  - Fly ash from coal-fired thermal power plants can be used for the removal of 2
      chlorophenol (2-CP) and 2,4-dichlorophenol (2,4-DCP) with enthalpy changes of
      about -3 kcal/mol. The amounts of 2-CP and 2,4-DCP removed are affected by the pH
      value of the solution. The efficiency of removal improves when the pH value is
      less than the pK(a) values of 2-CP and 2,4-DCP, respectively. The adsorbed amount
      of chlorophenol by fly ash is also affected by particle diameter, carbon content,
      and the specific surface area of the ash used in this study. As expected, more
      adsorption takes place with fly ash of higher carbon content and larger specific
      surface area. Moreover, the adsorbed amount of chlorophenol is not influenced by
      the matrix in the wastewater, as shown by studying the removal of 2-CP and 2, 4
      DCP in wastewater from a synthetic fiber plant. Chlorophenols in the wastewater
      were also removed efficiently through a fly ash column, with breakthrough times
      being inversely proportional to flow rates.

PMID- 10936537
TI  - Controlled low-strength material using fly ash and AMD sludge.
AB  - Controlled low-strength material (CLSM) is a cementitious material with
      properties similar to stabilized soil. After hardening, CLSM provides adequate
      strength in bearing capacity and support but can also be easily excavated. To be
      classified as a CLSM, the material must have a compressive strength between 450
      kPa (65 psi) and 8400 kPa (1200 psi). Typical CLSM contains coal-combustion fly
      ash (FA), cement, water and fine or coarse aggregate. In this paper, physical and
      strength properties of CLSM formed by combining sludge, a by-product from the
      treatment of acid mine drainage (AMD), with Class F FA are investigated. The
      sludge is a lime-based waste product that when combined with FA, exhibits self
      hardening characteristics similar to cement. A main focus of this research is to
      develop a CLSM mix in which by-product material utilization is maximized while
      satisfying workability and performance requirements. A mixture of 10% AMD sludge,
      2.5% Portland cement (PC), 87.5% Class F FA (dry wt.%) with water provided
      unconfined compressive strength values within the range for classification as
      CLSM. This mixture satisfies the excavatability and walkability requirements as
      well as the hardening time and stability criteria.

PMID- 10936538
TI  - MSW fly ash stabilized with coal ash for geotechnical application.
AB  - The solidification and stabilization of municipal solid waste (MSW) fly ash for
      the purpose of minimizing the geo-environmental impact caused by toxic heavy
      metals as well as ensuring engineering safety (strength and soaking durability)
      are experimentally evaluated. The mixtures of MSW fly ash stabilized with cement
      and fluidized bed combustion coal fly ash (FCA) were used for unconfined
      compressive strength tests, leachate tests, and soaking tests. The behavior of
      soluble salts contained in the MSW fly ash significantly affects strength
      development, soaking durability, and the hardening reaction of the stabilized MSW
      fly ash mixtures. The cement stabilization of the MSW fly ash does not have
      enough effect on strength development and soaking durability. The addition of
      cement only contributes to the containment of heavy metals due to the high level
      of alkalinity. When using FCA as a stabilizing agent for MSW fly ash, the mixture
      exhibits high strength and durability. However, the Cd leachate cannot be
      prevented in the early stages of curing. Using a combination of cement and FCA as
      a MSW fly ash stabilizer can attain high strength, high soaking durability, and
      the containment of heavy metals. The stabilized MSW fly ash with cement and FCA
      can be practically applied to embankments.

PMID- 10936539
TI  - Improvement of soft ground using solidified coal ash and its effects on the
      marine environment.
AB  - This paper presents some research results pertaining to the application of
      solidified coal ash (SCA) for improving the stability of soft ground. The results
      pertain to the physical properties of SCA required for use as an alternative to
      sand in sand compaction piles (SCPs), and the assessment of possible
      environmental impacts resulting from construction of SCA piles in marine
      environments. The results of field tests indicate that the physical properties of
      SCA (permeability, internal friction angle, and grain-size distribution) are
      favorable for use in soil improvement applications. Also, the results show that
      SCA is sufficiently suitable as an alternative to sand in SCPs, although SCA
      piles cannot be compacted to the same extent as sand piles. Finally, test results
      showed no adverse environmental impacts on natural benthos resulting from
      placement of SCA piles in marine environments. Thus, the results of this study
      confirm that SCA is a viable alternative material to sand in SCPs that are used
      for ground improvement in marine environments, and that large quantities of SCA
      may be required for such applications resulting in an alternative use for an
      otherwise waste material.

PMID- 10936540
TI  - Effective use of fly ash slurry as fill material.
AB  - A lot of effort has been put into increasing coal ash utilization; however, 50%
      of total amount is disposed of on land and in the sea. Several attempts have been
      reported recently concerning slurried coal fly ash use for civil engineering
      materials, such as for structural fill and backfill. The authors have studied
      this issue for more than 15 years and reported its potential for (1) underwater
      fills, (2) light weight backfills, and (3) light weight structural fills, through
      both laboratory tests and construction works. This paper is an overview of the
      results obtained for slurry, focusing on the following. (1) Coal fly ash
      reclaimed by slurry placement shows lower compressibility, higher ground density,
      and higher strength than by the other methods. This higher strength increases
      stability against liquefaction during earthquake. (2) Higher stability of the fly
      ash ground formed by slurry placement is caused by higher density and its self
      hardening property. (3) Stability of fly ash reclaimed ground can be increased by
      increasing density and also by strength enhancement by cement addition. (4)
      Technical data obtained through a man-made island construction project shows the
      advantages of fly ash slurry in terms of mechanical properties such as higher
      stability against sliding failure, sufficient ground strength, and also in terms
      of cost saving. (5) Concentration in leachates from the placed slurry is lower
      than the Japanese environmental law. (6) In order to enlarge the fly ash slurry
      application toward a lightweight fill, mixtures of air foam, cement and fly ash
      were examined. Test results shows sufficient durability of this material against
      creep failure. This material was then used as lightweight structural fill around
      a high-rise building, and showed sufficient quality. From the above data, it can
      be concluded that coal fly ash slurry can be effectively utilized in civil
      engineering projects.

PMID- 10936541
TI  - Effects of the initial level of milk production and of the dietary protein intake
      on the course of natural nematode infection in dairy goats.
AB  - The level of dietary protein is known to alter the establishment and the
      pathophysiology of gastrointestinal nematodes in sheep. On the other hand, high
      producing dairy goats are less resistant and/or resilient than low-producing ones
      to experimental nematode infection. During a 2-year study, we have investigated
      the course of a natural nematode infection (mainly T. colubriformis) in a high
      producing dairy goat flock. In year 1, 50 grazing goats divided in high (HP) or
      low producer (LP) were compared from April to October for parasitological and
      milk parameters. In year 2, the 25 HP goats were only considered and were
      allocated to two levels of dietary protein, high level (HPr) with a protein
      coverage of 125% or normal level (NPr) with a protein coverage of 106%. They were
      monitored as above. In year 1, HP goats showed a greater nematode egg output
      (1856 vs. 1000epg) associated with higher values in T. colubriformis IgG in
      autumn than LP ones whereas the decrease in serum phosphate concentration was
      similar in both groups. In year 2, HPr goats exhibited lower egg output in autumn
      (2219 vs. 2817) vs. NPr ones. Moreover, milk yield and fat content were
      significantly higher in HPr vs. NPr in the 2nd part of the study. HP goats are
      less resistant to nematode infection in natural conditions. Resistance and
      resilience of HP goats may partially be improved by a protein supplementation in
      the diet.

PMID- 10936543
TI  - Effects of the depletion of CD8(+) T cells and monocytes on the proliferative
      responses of peripheral blood leucocytes from Trypanosoma evansi-infected sheep.
AB  - Sheep peripheral blood mononuclear cells and those depleted of CD8(+) T cells
      and/or monocytes were stimulated with polyclonal mitogens and specific antigens,
      and analysed by means of cell proliferation assay procedure to examine whether
      these cell populations are involved in Trypanosoma evansi-induced
      immunosuppression. The removal of CD8(+) T cells failed to normalize the
      proliferative responses of peripheral blood mononuclear cells from infected sheep
      to concanavalin A stimulation while the depletion of monocytes resulted in full
      and enhanced response, showing that macrophages are mainly responsible for the
      suppression. Although the depletion of CD8(+) T cells, monocytes or both restored
      the responses of the cells to lipopolysaccharide stimulation, the responsiveness
      of the undepleted cells to this mitogen was significantly higher from day 24 post
      infection (p<0.01). The results were discussed in relation to current known
      mechanisms of depressed lymphocyte proliferation in tsetse-transmitted African
      trypanosome infections.

PMID- 10936542
TI  - Attempts to control haemonchosis in grazing ewes by vaccination with gut membrane
      proteins of the parasite.
AB  - A vaccination trial was conducted to evaluate the potential benefit of Haemonchus
      contortus gut membrane proteins as vaccine antigens under field conditions in
      Louisiana. The trial was conducted in the summer of 1996 in a flock of ewes
      grazing pasture naturally infected with H. contortus. Ewes were randomly assigned
      to three treatment groups (vaccine, adjuvant only, and saline) and fecal egg
      counts (FEC, measured as eggs per gram of feces), packed cell volumes (PCV), and
      antibody levels were monitored fortnightly for 12 weeks. It was shown by FEC that
      there were large individual variations in susceptibility to H. contortus in both
      vaccinated and non-vaccinated sheep, a finding which could have masked
      differences between treatments when analyzed by conventional statistical methods.
      Based on their egg counts before the period when the vaccination could have had
      an effect, all ewes were categorized as 'susceptible' or 'relatively resistant'.
      The significance of differences between FEC, PCV and antibody responses of
      vaccinated and control sheep were tested separately for the 'susceptible' and
      'relatively resistant' category. The 'susceptible' vaccinates shed 65% fewer worm
      eggs during the period when the vaccine could have had an effect, but the
      difference was only significant on Week 6 post-vaccination. In these experiments,
      it was difficult to completely exclude the confounding effect of having
      'relatively resistant' sheep in the control group. More studies are needed to
      further evaluate H11 and H-gal-GP antigens under field conditions.

PMID- 10936544
TI  - Inhibition of Eimeria tenella replication after recombinant IFN-gamma activation
      in chicken macrophages, fibroblasts and epithelial cells.
AB  - We have previously shown that activation of primary cultures of chicken bone
      marrow macrophages and embryo fibroblasts with supernatants of concanavaline A
      stimulated or reticuloendotheliosis virus (REV)-transformed chicken spleen cells
      as source of IFN-gamma significantly decreases Eimeria tenella growth in vitro.
      In the present study, we used various chicken cell lines, HD11 macrophages and
      DU24 fibroblasts, both virally transformed, CHCC-OU2 fibroblasts and LMH hepatic
      epithelial cells, both chemically transformed, to replicate E. tenella in vitro.
      We confirmed the previous results by showing that HD11 macrophages pre-treated
      for 24h with recombinant chicken IFN-gamma (either produced in E. coli or by
      transfected COS cells), at doses ranging from 1000 to 10U/ml, drastically
      inhibited E. tenella replication as measured by [3H] uracil uptake after a
      further 70h of culture, as when treated with REV supernatant. Likewise the
      fibroblast and epithelial cell lines exhibited significant inhibitory activity on
      E. tenella replication after pre-treatment with recombinant chicken IFN-gamma,
      but were less sensitive (1000-100U/ml) than when treated with REV supernatant.
      Recombinant chicken IFN-alpha pre-treatment of all cell lines had no inhibitory
      effect on parasite development.

PMID- 10936545
TI  - Prevalence of selected species of internal parasites in equids at necropsy in
      central Kentucky (1995-1999).
AB  - A survey to determine current prevalence of several species of endoparasites in
      equids (n=350) at necropsy was conducted at the Livestock Disease Diagnostic
      Center in central Kentucky (1995-1999). Thelazia lacrymalis were found in 42% of
      the 1- to 4-year olds (n=132), which was the only age group examined for these
      parasites. Five- to 30-year olds (n=157), examined for Onchocerca spp.
      worms/lesions, had a prevalence of 24%. In > or =1-year olds (n=324), the
      infection rate for Gasterophilus intestinalis was 12% for second instars and 14%
      for third instars and for Gasterophilus nasalis was 2% for second instars and 2%
      for third instars. For Anoplocephala perfoliata (n=268 equids), prevalence was
      52%. Data were compiled for the equids according to breed, age, sex, month of
      necropsy, and number of parasites. Arterial lesions caused by migrating
      Strongylus vulgaris larvae were observed in a low number (3 of 52) of equids.
      Specific examination for Parascaris equorum revealed that 46% of 13 weanlings and
      10% of 20 older horses were infected. Anoplocephala magna were found in one of
      the weanlings. Compared to previous studies (about 15-25 years ago) in Kentucky,
      the present survey indicated the genera Onchocerca and Gasterophilus greatly
      declined but Thelazia, Anoplocephala, and Parascaris did not.

PMID- 10936546
TI  - Detection of space-time clusters and epidemiological examinations of scabies in
      chamois.
AB  - In this paper some methodological approaches towards the detection of temporal,
      spatial and space-time clusters are presented and discussed in context with
      epidemiological factors of scabies in chamois. This presentation comprises in
      particular the use of the Scan Test (Wallenstein, 1980) for the detection of
      temporal clusters and the tests developed by Knox (1964) and Mantel (1967) for
      the testing of spatiotemporal interactions. Between 1952 and 1998 a total of 1689
      cases of scabies in chamois and six cases in ibex were documented in 137 game
      preserves of the Austrian province of Styria. The evaluations indicate the
      presence of spatial and temporal clusters. Some possibilities for the spread of
      scabies in chamois are presented and reveal ibex as a probable vector for scabies
      transmission between chamois populations. The information may lead to strategies
      for controlling the spread of the disease.

PMID- 10936547
TI  - Quantitative comparison of various methods for detecting eggs of Toxocara canis
      in samples of sand.
AB  - Six techniques for recovering unembryonated Toxocara canis eggs from sand samples
      were tested for efficiency and suitability for routine use. The tests were done
      under standardised conditions on 50g of sand samples contaminated experimentally
      with 10, 100 and 500 eggs of T. canis. Best result was achieved by the method of
      Dunsmore et al. [Dunsmore, J.D., Thompson, R.C.A., Bates, I.A., 1984. Vet.
      Parasitol. 16, 303-311]. The results were expressed as the number of T. canis
      eggs recorded and percentage rates of recovery in sand samples.

PMID- 10936548
TI  - Canine dirofilariosis in two cities of southeastern Spain.
AB  - Several cases of human subcutaneous/ocular dirofilariosis caused by Dirofilaria
      repens from an area in the southeastern Spain where previous epidemiological
      studies have shown a very low prevalence of this species in dogs, have been
      studied in our laboratory. Since the prevalence of this species in dogs did not
      correspond to the incidence of human cases in the zone studied, a preliminary
      epidemiological survey was carried out on 114 dog blood samples from two kennels
      and one veterinary clinic. Knott, polymerase chain reaction (PCR) with specific
      primers for Dirofilaria immitis and D. repens, and ELISA with adult E/S D.
      immitis and adult somatic D. repens antigens for the detection of specific IgG,
      were used. Fifty-three out of the 114 samples analyzed were positive for Knott
      and/or PCR to D. immitis or to D. repens. D. repens was the species with the
      highest prevalence, 84.6 and 37.1%, respectively, in each kennel. IgG antibodies
      against D. immitis and D. repens, were detected in 11 samples which gave negative
      results to both Knott and PCR. These results demonstrate a very high prevalence
      of D. repens that could be associated with the increasing incidence of human
      subcutaneous/ocular cases recently detected in this zone.

PMID- 10936560
TI  - Liver weight of adult Japanese, especially recent weight values.
AB  - Cases of 445 adult Japanese autopsies of the Tokyo Metropolitan Medical
      Examiner's Office were used in this study. They were either negative for all
      hepatitis virus-related markers examined or had little or no histopathological
      hepatic changes. The maximum liver weight was observed in the fifth decade in
      both sexes, and after the fifth decade the liver weight decreased markedly with
      increasing age. The sexual difference in the liver weight was most predominant in
      the third to fifth decades, but the sexual difference was not marked in the older
      age groups. The highest liver weight to body weight ratio was observed in the
      fifth decade of both sexes, and a total decadal pattern of the ratio was similar
      to a parabola. An interesting finding was that the male liver weights in the
      third to fifth decades considerably increased in recent years, but the female
      liver weights in the third decade were almost the same despite the difference in
      investigation period. We suggest the data of this study may be a standard for
      Japanese people.

PMID- 10936561
TI  - The effects of chronic hepatitis C and B virus infections on liver reduced and
      oxidized glutathione concentrations.
AB  - The aim of this study was to evaluate the effects of hepatitis B and C virus
      infections on liver glutathione status. Reduced and oxidized glutathione levels
      were determined in liver biopsy specimens obtained from patients with chronic
      liver disease including chronic active hepatitis and cirrhosis. In patients with
      hepatitis B virus infections, GSH and GSH/GSSG levels were significantly low
      compared with those in controls (P<0.01). There was a significant negative
      correlation between histological activity indices (HAI) and hepatic GSSG levels
      only in patients with chronic HCV infection (P<0.01; r=-0.895). In addition to
      this, we also found a positive correlation between indices (HAI) and GSH/GSSG of
      the same group (r=0.915; P<0.05). These observations suggest that HBV and HCV
      infections have different effects on liver glutathione status based on diverse
      mechanisms.

PMID- 10936562
TI  - Differences in survival based on the type of follow-up for the detection of
      hepatocellular carcinoma: an analysis of 547 patients.
AB  - The aim of this study was to identify any significant variables in the prognosis
      of 547 cases with hepatocellular carcinoma (HCC), and simultaneously confirm the
      survival among the different surveillance modalities for the initial detection of
      HCC in a closely followed-up group (regular periodic follow-up with monthly alpha
      fetoprotein (AFP) and ultrasonography at least every 4 months), a not closely
      followed-up group (neither performed with AFP nor ultrasonography regularly) and
      an incidental group (incidentally discovered due to related symptoms). Five
      hundred and forty-seven consecutive patients with HCC diagnosed at the Internal
      Medicine Department of Saga Prefectural Hospital Koseikan from January 1989 to
      December 1998 were retrospectively analyzed. The 1-, 3- and 5-year survivals in
      all 547 cases were 69.7, 42.4 and 26.9%, respectively. The 1-, 3- and 5-year
      survivals in the cases found to have solitary HCC measuring 2 cm or less in
      diameter at the time of diagnosis were 97.3, 76.2 and 52.3%, respectively. Forty
      seven point one percent of the closely followed-up group, which was the high-risk
      group were found to have solitary HCC measuring 2 cm or less in diameter (48 out
      of the 102 followed-up cases), while only 18.5 and 11.8% were found in the not
      closely followed-up group (46 out of 248 cases) and the incidental group (22 out
      of 186 cases), respectively. The 5-year survival in the closely followed-up, the
      not closely followed-up and the incidental groups were 42.9, 26.1 and 15.3%,
      respectively. The significant factors obtained in the closely followed-up group
      compared to those from the not closely followed-up group included AFP, tumor
      size, tumor number and portal thrombosis. These findings indicate the importance
      of a close follow-up for high-risk groups in order to identify HCC at an early
      stage, and thereby have a positive influence on survival.

PMID- 10936563
TI  - TT virus infection among renal transplant recipients.
AB  - To clarify the prevalence of TT virus (TTV) infection in renal transplant
      recipients and to estimate the role of TTV in patients with post-transplant liver
      function abnormalities, TTV-DNA of 47 renal transplant recipients was screened by
      polymerase chain reaction (PCR) according to a method described by Okamoto et al.
      before and after the renal transplantation. One of them was positive for
      hepatitis B surface antigen (HBsAg), one was positive for anti-hepatitis C virus
      (HCV) and other 45 were negative for both HBsAg and anti-HCV. TTV-DNA was
      detected in 22 of 47 patients before renal transplantation, and nine became
      positive after transplantation. All 47 patients showed a normal level of ALT
      before transplantation. Three of nine (33%) who became positive for TTV-DNA after
      transplantation and three of 16 (19%) who were negative for TTV-DNA before and
      after transplantation showed transient elevation of ALT. These results indicate
      that TTV was highly prevalent among renal transplant recipients, but a clear
      association between TTV and post-transplant liver function abnormality was not
      found.

PMID- 10936564
TI  - Comparative study on the correlation of plasma gamma-aminobutyric acid and
      pipecolic acid with liver function in patients with liver cirrhosis.
AB  - gamma-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, elevated in
      plasma of patients with liver cirrhosis. Pipecolic acid (PA), a metabolite of
      lysine, and known to be a GABA receptor agonist, is also seen high levels in the
      plasma. To clarify the relationship of GABA, PA and liver function, plasma GABA
      and PA in three groups of chronic liver diseases (compensated cirrhosis,
      decompensated cirrhosis and decompensated cirrhosis with hepatic encephalopathy,
      HE) were analyzed and their liver functions were compared. This analysis
      demonstrated that both plasma GABA and PA were higher in these patients than in
      normal subjects. Plasma PA, but not plasma GABA, was closely correlated with
      plasma ammonia concentration in each group. No correlation was noted between
      plasma GABA and PA in each group. Plasma pipecolic acid was significantly higher
      in patients with esophageal varices than in patients with no varices. These
      findings suggest that increased PA may reflect the degree of portal hypertension.
      Although both GABA and PA are increased in chronic liver disease, they may have a
      different origin and disappearance rate including metabolic mechanism.

PMID- 10936565
TI  - HCV in serum, peripheral blood mononuclear cells and lymphocyte subpopulations in
      C-hepatitis patients.
AB  - To define the best marker for the follow-up and evaluation of HCV infections we
      determined anti-HCV antibodies, serum transaminases and HCV RNA in patients
      diagnosed with chronic hepatitis for C virus and treated with alpha-interferon.
      The presence/absence of HCV RNA was determined in serum, peripheral blood
      mononuclear cells (PBMC) and lymphocyte subpopulations. Samples were submitted to
      RT-PCR and subsequent nested PCR. Treatment with alpha-interferon induced a fall
      in the number of HCV RNA positive patients from an initial 88 to 25% at the end
      of the treatment. The withdrawal of treatment was associated with a significant
      increase in the number of HCV RNA positive patients (43% at the 12-month follow
      up). In 61% of the patients the PCR analysis of the PBMC population detected the
      presence of HCV RNA. In 87% of cases the cell fraction identified as CD19
      resulted positive in the PCR test and the viral genome was undetectable in PBMC
      subpopulations in only 13% of cases. In one third of the patients whose serum was
      negative for PCR the analysis demonstrated the presence of HCV RNA in PBMC.
      Conclusions: The disappearance of the viral genome in serum, a criterion of
      treatment response, is not necessarily followed by its disappearance in PBMC. The
      joint determination of HCV by PCR technique in serum and blood cells should be
      used as a particular instrument with each patient.

PMID- 10936566
TI  - A long-term survival case of multiple hepatocellular carcinoma with metachronous
      lymph node metastasis.
AB  - A long-term survival case of multiple hepatocellular carcinoma (HCC) with
      metachronous metastasis to a lymph node is reported. The patient, a 66-year-old
      woman, had two primary HCC nodules, one each in the left and right hepatic lobes,
      which were resected. She developed a lymph node lesion and a secondary HCC 45 and
      62 months after the first operation, respectively. She has been well for the 7
      years since the first operation despite undergoing hepatic resection for HCC
      twice as well as lymph node resection. Clonal analysis, based on the methylation
      pattern of the X chromosome-linked androgen receptor gene, suggested that the two
      primary tumors were multicentric and that the lymph node lesion had arisen by
      metastasis from the primary tumor in the right hepatic lobe.

PMID- 10936568
TI  - Antifilarial activity of some 2H-1-benzopyran-2-ones (coumarins).
AB  - Six synthetic 2H-1-benzopyran-2-one (cournarin) derivatives (CDRI compounds # 1,
      2, 3, 4, 5 and 6) were evaluated for filaricidal activity against Litomosoides
      carinii and Acanthocheilonema viteae infections in cotton rats (Sigmodon
      hispidus) and Mastomys coucha respectively. Significant effects on macrofilariae
      (>80% death/sterilisation) were detected with compounds #2, 3 and 6 against L.
      carinii and/or A. viteae. Thus detection of filaricidal activity in benzopyrones,
      which are so far known for anti-inflammatory activity, provides a new lead for
      development of better filaricidal agents for combating filariasis.

PMID- 10936567
TI  - Schistosoma japonicum infection in the pig as a model for human schistosomiasis
      japonica.
AB  - Valuable information on human schistosomiasis japonica has been provided using
      primates and experimental rodent hosts. However, major drawbacks such as high
      costs and ethical concerns for the primate models and large biological deviations
      for the rodent models have led to the search for more appropriate models. Recent
      data on the pig indicate that this natural host for Schistosoma japonicum might
      be a realistic alternative. As only very few research groups have investigated
      the S. japonicum/pig model, the present review mainly deals with the experimental
      methods and the major host/parasite findings obtained from the authors own
      research group. With emphasis on a critical evaluation of the work, the results
      are compared to the scarce information existing on human schistosomiasis
      japonica. Like in humans, S. japonicum establishes mainly in the large intestinal
      veins, with high faecal egg counts during the acute phase of infection, which
      varies greatly within and between days. Concomitant resistance is another shared
      feature, but studies in pigs have indicated that the phenomenon is more complex
      than generally thought. Clinical signs as eosinophilia and diarrhoea with mucus
      and blood in the acute phase of infection and hepatomegaly, increased portal
      diameter, periportal fibrosis and ascites in chronic infections are common
      findings in both humans and pigs. Low protein diet aggravates the disease in pigs
      by increasing the establishment rates, the faecal egg excretion and the
      morbidity. A 100% cure rate is achieved when treating S. japonicum infected pigs
      with praziquantel at 40 mg/kg, and 4 weeks post treatment pigs remain resistant
      to reinfection. Lastly, human congenital S. japonicum infection has been
      confirmed in pigs but the implications of such infections for the pathogenesis of
      schistosomiasis japonica remain to be investigated.

PMID- 10936569
TI  - Tegumental changes in adult Schistosoma mansoni harboured in mice treated with
      praziquantel enantiomers.
AB  - Praziquantel administered to the host causes damage to the tegument of
      Schistosoma mansoni. In this study, the effects of racemic praziquantel (Pra) and
      its enantiomers, levo-praziquantel (L-Pra) and dextro-praziquantel (D-Pra) were
      compared using scanning electron microscopy (SEM). Mice infected with S. mansoni
      for 49 days were treated with a single dose of Pra (300 mg/kg), L-Pra (150 mg/kg)
      or D-Pra (150 or 600 mg/kg). Groups of three mice were killed after 4 and 24 h,
      and schistosomes collected by perfusion and examined by SEM. Treatment with Pra
      or L-Pra, for 4 or 24 h, caused tegumental damage to S. mansoni including severe
      swelling, vacuolization, fusion of the tegumental ridges and loss or shortening
      of the spines on the tubercles, collapse and peeling. After treatment with D-Pra
      at 150 mg/kg, no apparent damage was observed. When the dosage was increased to
      600 mg/kg, after 4 h lesions on the tegument similar to those induced by Pra or L
      Pra were seen, but less severe. After 24 h, there was evidence of recovery. The
      study thus clearly showed that L-Pra was more active than D-Pra in causing
      tegumental damage. D-Pra showed a qualitatively similar activity at a higher
      concentration. It is possible that this effect was due at least to some extent to
      the small amount of L-Pra (<2%) which was present in the preparation of D-Pra
      used.

PMID- 10936570
TI  - Longstanding presence of HIV-2 infection in Guinea-Bissau (West Africa).
AB  - We have retrospectively studied the seroprevalence of the human immunodeficiency
      virus (HIV) in Guinea-Bissau in a sample of sera collected from the whole country
      in 1980. We tested a total of 1248 individuals and found 11 individuals who were
      seropositive for HIV-2 but there were no HIV-1 seropositive samples. The mean age
      of the HIV-2 seropositive people was significantly higher than the age of the
      seronegative individuals. In the different areas surveyed, the HIV-2
      seroprevalence ranged from 0 to 2.5%. A central region of the country, grossly
      centred in the capital city of Bissau, presented the highest prevalence of HIV-2
      seropositivity (>2%), which contrasts with its virtual absence from the more
      remote rural areas located near the borders with the neighbouring countries. The
      overall seroprevalence found for HIV-2 in this study is 0.9% (1.8%, when
      considering the adult seroprevalence only), which proves that the virus was
      definitely circulating in Guinea-Bissau at the beginning of the 1980s.

PMID- 10936571
TI  - The role of pigs as transport hosts of the human helminths Oesophagostomum
      bifurcum and Necator americanus.
AB  - We conducted a study in an endemic area of both Oesophagostomum bifurcum and
      Necator americanus in northern Ghana to examine the possibility of pigs acting as
      transport hosts for these two human helminth species, due to the commonly
      observed coprophagic habits of pigs. Under controlled conditions four parasite
      free pigs consumed fresh faeces from people heavily infected with both helminths,
      and faeces were subsequently collected from the rectum of the pigs from 5 to 50 h
      post-feeding. Four to five per cent of the O. bifurcum and N. americanus eggs fed
      to the pigs were viable and retrieved as third-stage larvae after coproculture of
      the pigs' faeces. We discuss the possible impact of the coprophagic habits of
      pigs as potential parasite transport hosts during different seasons in this area
      of West Africa.

PMID- 10936572
TI  - In vitro leishmanicidal activity of monomeric and dimeric naphthoquinones.
AB  - A series of monomeric and dimeric naphthoquinones with potential for treatment of
      Leishmania infections was identified in vitro using both a direct cytotoxicity
      assay against extracellular promastigotes of Leishmania donovani, Leishmania
      infanturn, Leishmania enriettii, and Leishmania major and a test against
      intracellular amastigote L. donovani residing within murine macrophages. Several
      naphthoquinones proved to be active at concentrations in the microgram range
      (EC(50) 0.9-17.0 microg/ml). When tested against a panel of human cancer cell
      lines (KB, SKMel, A549, MDA) and murine bone marrow culture-derived macrophages
      (BMMPhi) as mammalian host cell controls, compounds with anti-Leishmania-activity
      showed moderate (EC(50)>25 microg/ml) to pronounced (EC(50)<10 microg/ml) toxic
      effects.

PMID- 10936573
TI  - Stage specific kinetoplast DNA-binding proteins in Trypanosoma cruzi.
AB  - Knowledge regarding kinetoplast DNA organization in all members of the
      Trypanosomatid family is incomplete. Recently, the presence of kinetoplast
      associated proteins in condensing kDNA networks in Crithidia fasciculata has been
      described and a role for these proteins in the maintenance of these complex
      structures was suggested. To investigate the presence of protein components in
      Trypanosoma cruzi kinetoplast, we previously described seven epimastigote
      kinetoplast-associated proteins. We report here the existence of kinetoplast
      binding proteins in amastigote and trypomastigote stages of T. cruzi, which could
      bind both mini and maxicircles components with a stage specific elements for
      every infective form of the parasite. We propose three major classes of
      kinetoplast-associated proteins related to the basic processes of this intricate
      disc structure and suggest a possible function of these binding proteins in the
      T. cruzi mitochondrial DNA organization.

PMID- 10936574
TI  - Potential risks of viral infections in xenotransplantation.
AB  - The shortage of cadaveric human organs for transplantation may, be alleviated by
      the use of xenografts as a therapeutic option for end-stage organ failure.
      Successful attempts have been made to prevent rejection of xenograft tissues in
      humans. The potential spread of animal-derived pathogens to the xenograft
      recipient is a complication of xenotransplantation, which must be addressed. This
      can be complicated further by, the presence of new pathogens, new clinical
      syndromes, and altered behaviour of these organisms in the immunocompromised
      recipient. There is concern over the possible activation of latent viruses,
      including retroviruses, from xenograft tissues. This paper discusses the possible
      dangers of transmission of animal viruses to humans via xenotransplantation.

PMID- 10936575
TI  - The influence of self-fertilization and pairing on life-history traits in the
      freshwater snail Bulinus forskalii (Gastropoda, planorbidae).
AB  - This study analyses the basic reproductive biology of the schistosonie-vector
      snail Bulinus forskalli. This hermaphroditic species can self-fertilize.
      Variation of the mating system was analysed in two populations from Cameroon in a
      three-step experiment. (i) The fecundity (number of eggs and of egg capsules) of
      isolated virgin individuals from both populations was followed over a month, as
      well as the survival of offspring from these individuals. Estimates of these
      parameters were intermediate. Our results also indicate that inbreeding
      depression has a maximum value of about one-half in both populations. No
      difference was observed between populations for both the overall fecundity of
      adults and survival of offspring. (ii) Individuals were then paired either
      within, or between populations over three successive days, and the number of
      copulations recorded. Copulations were observed in all situations, including
      between-population pairs. No significant dlifference in the number of copulations
      per pair was detected. However, this value decreased with time, and reciprocal
      copulations were significantly less numerous between than within populations.
      (iii) Individuals that successfully copulated as female in (ii) were isolated,
      and their fecundity was followed over 3 weeks. The fecundity of individuals that
      had been maintained isolated over the whole experiment served as a control. No
      significant difference was on the whole detected. Our results collectively
      suggest that the individuals from the two populations studied are rather selfers,
      confirming that B. forskalii is a preferentially selfing species. There is also
      some pre-zygotic isolation against crosses between populations.

PMID- 10936576
TI  - Factors affecting adverse event reporting during mass ivermectin treatment for
      onchocerciasis.
AB  - This study examines the effect of age, sex, dosing round, time of day, and
      distance from the nurse monitor on adverse event reporting during mass ivermectin
      administration at Achi, south-east Nigeria. There was a significant increase in
      adverse event reporting with age but no significant difference between the sexes.
      Both compliance and the incidence of reported adverse events were less during the
      second dosing round than during the first. Only three (2%) out of 144 subjects
      interviewed gave adverse events as a reason for non-compliance. Significantly
      fewer adverse events were reported as starting at night (22:00-06:00 h) than by
      day. The effect of distance on adverse event reporting was not statistically
      significant for distances up to 1 km.

PMID- 10936577
TI  - Preliminary evaluation of LATEX/T. b. gambiense and alternative versions of
      CATT/T. b. gambiense for the serodiagnosis of human african trypanosomiasis of a
      population at risk in Cote d'Ivoire: considerations for mass-screening.
AB  - A study was conducted to compare classical card agglutination test for
      trypanosomiasis (CATT)/T. b. gambiense with CATT-EDTA and LATEX/T. b. gambiense
      as alternative field tests for serodiagnosis of Human African Trypanosomiasis.
      The tests were performed on freshly collected blood in an endemic and a low
      prevalence area in Cote d'Ivoire. Diagnostic performance of each test was
      assessed using Quantitative Buffy Coat as the parasitological reference and
      immune trypanolysis as the serological reference test. According to the
      parasitological data, CATT-EDTA on 10 microl and LATEX/T. b. gambiense on blood
      diluted 1:4, detecting all confirmed cases with good specificity (respectively
      94.6% and 98.1%) yielded better results than the classical CATT did (one false
      negative and 92.5% specific). However, when immune trypanolysis data and
      feasibility are taken into account, the classical CATT remains the test of choice
      for mass screening under the given field conditions.

PMID- 10936578
TI  - Malaria in Sao Tome and Principe: parasite prevalences and vector densities.
AB  - A cross-sectional survey was carried out in 16 localities on the island of Sao
      Tome and three on the island of Principe, at the end of the rainy season of 1997,
      to determine malaria prevalence and vector densities. Blood samples from 664
      inhabitants of all ages were examined by optical microscopy (OM) and PCR.
      Mosquito collections were made by outdoor landing captures from 21:00-23:00 h.
      Great differences were found between OM and PCR readings. OM had a sensitivity of
      66%, a specificity of 79% and failed to reveal any mixed-infections. Overall
      prevalence, determined by PCR, was higher in Sao Tome (53%) than in Principe
      (35%). It was highest in children below 16 years-old. All four human Plasmodium
      species occurred in Sao Tome but P. ovale was not detected in Principe. The human
      population was largely asymptomatic. Bednet users had lower prevalence than did
      non-users. The FOREST form of Anopheles gambiae s.s., identified by PCR and
      cytogenetics, was the only vector on the islands. The sporozoite rate in Sao
      Tome, assessed by ELISA, was 0.5%. Parasite prevalence and vector densities were
      positively correlated in Sao Tome, where malaria transmission must occur
      predominantly in the more populated coastal areas.

PMID- 10936579
TI  - Leishmania donovani in blood smears of asymptomatic persons.
AB  - Leishmania amastigotes have been detected in the peripheral blood smears of
      Indian kala-azar patients mostly during night. It was, therefore, thought
      worthwhile to find out whether such amastigotes could be shown in healthy
      subjects who did not have any symptoms by history or signs on clinical
      examination. Leishmania-stained blood smears of 450 asymptomatic healthy
      individuals residing in an endemic village in Bihar (India) were examined by oil
      immersion microscopy for the detection of amastigote, six people (1.3%) showed
      the presence of Leishmania amastigotes. Given the low sensitivity of a single
      smear examination it is likely that a much greater proportion of asymptomatic
      persons had parasitemia than the observed 1.3%. This finding is important from
      the point of view of transmission of disease, as also for modifying the current
      control measures.

PMID- 10936580
TI  - Effect of lymphatic filariasis on school children.

PMID- 10936581
TI  - Simple and practical sandwich-type enzyme immunoassay for human oxidatively
      modified low density lipoprotein using antioxidized phosphatidylcholine
      monoclonal antibody and antihuman apolipoprotein-B antibody.
AB  - OBJECTIVES: To develop a simple and practical enzyme immunoassay (EIA) for
      oxidatively modified low density lipoprotein (Ox-LDL) in human blood, a
      biological marker of atherogenesis. DESIGN AND METHODS: A sandwich EIA suitable
      for the measurement of human Ox-LDL was developed using the mouse monoclonal
      antibody FOH1a/DLH3. This antibody, specific for oxidized phosphatidylcholine,
      was used as the capture antibody, and a horseradish peroxidase (HRP)-labeled goat
      anti-human apolipoprotein-B (Apo-B) IgG was used for detection. Copper-oxidized
      human LDL, prepared under controlled conditions, was used as a standard and the
      results of the EIA were expressed in arbitrary units (U/mL). RESULTS: This EIA
      meets all the requirements for use in routine clinical assays in terms of
      sensitivity (detection limit: 1 U/mL), reproducibility (total CV: 2.3-7.7%),
      accuracy (recovery: 90.6-103.8%), simplicity and rapidity (<4 h). Clinical
      performance of the assay was assessed by measurement of the Ox-LDL in the plasma
      of normal subjects (10.8 +/- 2.8 U/mL, mean +/- SD) and patients with coronary
      heart disease (CHD) (19.7 +/- 10.2). The present EIA had a sensitivity of 79% and
      a specificity of 75% for CHD. CONCLUSIONS: We have developed a new assay,
      suitable for the measurement of Ox-LDL in human blood, which meets the
      requirements for routine clinical assay.

PMID- 10936582
TI  - Use of a dual monoclonal solid phase and a polyclonal detector to create an
      immunoassay for the detection of human cardiac troponin I.
AB  - OBJECTIVES: We report the development of a fully automated, random access,
      chemiluminescent immunoassay, for the detection of human cardiac Troponin I
      (cTnI) in serum and plasma for use on the ACS:180(R) System. DESIGN AND METHODS:
      This assay format uses a combination of two monoclonal antibodies covalently
      coupled to paramagnetic (PMP) particles as a solid phase and an affinity purified
      polyclonal antibody, specific to the N-terminal domain of cTnI (peptide-3 region)
      labeled with a chemiluminescent compound as the detector antibody. The assay
      offers excellent low-end sensitivity and precision. RESULTS: No interferences are
      observed from by blood components such as HAMA and drugs used in cardiac therapy.
      Patient samples tested on the ACS:180 cTnI assay showed good correlation with the
      Stratus cTnI assay (ACS: cTnI = 1. 02*Stratus + 0.05 g/L, r = 0.96, n = 1170).
      CONCLUSION: Paired with the other ACS:180 cardiac assays, myoglobin and CKMBII,
      the ACS:180 system now offers an excellent panel of cardiac assay for use in
      rapid and accurate diagnosis of a myocardial event.

PMID- 10936583
TI  - Measurement of soluble transferrin receptor by immunoturbidimetry and
      immunonephelometry.
AB  - OBJECTIVE: To evaluate and compare two new commercially available
      immunoturbidimetric and immunonephelometric assays for measuring soluble
      transferrin receptor (sTfR) in serum. To adapt the immunonephelometric assay to
      an automated chemistry analyzer. DESIGN AND METHODS: Total imprecisions and
      detection limits were calculated and compared. Fifty-six samples were used for
      methods comparison. The nephelometric assay was adapted to the Hitachi 911
      analyzer. RESULTS: Both methods displayed acceptable imprecisions and detection
      limits. Their correlation was good but a proportional bias was observed. The
      adaptation of the nephelometric assay to the Hitachi 911 was successful.
      CONCLUSIONS: These two new immunoassays are analytically acceptable and more
      practicable than previously developed methods. The differences observed between
      both methods underscores the need for standardization. The nephelometric assay
      was easily adaptable to an automated chemistry analyzer.

PMID- 10936584
TI  - Urinary excretion of deoxypyridinoline in 24-hour and first-void samples in
      healthy Turkish children.
AB  - OBJECTIVES: Collagen cross-links are formed during the maturation process of bone
      matrix. They have been considered as valuable markers in some metabolic,
      endocrinologic, and neoplastic bone disorders. As an advantage, it can be
      measured in urine as well as in serum samples. However, the excretion
      characteristics remains controversial. DESIGN AND METHODS: We investigated
      urinary free deoxypyridinoline (f-Dpd) excretion in first-void urine samples and
      in 24-hour collections in healthy Turkish children. We also evaluated the
      possible correlations and gender-related differences in Dpd excretion between
      these sampling methods. Both urine samples of 62 subjects (aged from 31 to 120
      months) were analyzed by Immulite chemiluminescent technique. RESULTS: There were
      no remarkable differences in f-Dpd excretion between first-void and 24-hour urine
      samples, although f-Dpd values of the first-void samples were slightly higher
      (Dpd: creatinine, mean +/- SD, 20.5 +/- 5.8 nmol/mmol vs. 19.6 +/- 5.6 nmol/mmol,
      respectively, p > 0.05). A strong linear correlation was found between 24-hour
      and first-void urine f-Dpd excretions (r = 0.77, p < 0.05). In addition, f-Dpd
      showed no gender-related differences between boys and girls in either 24-hour or
      first-void urine samples (p > 0.05). CONCLUSIONS: Because of difficulties in long
      time urine collection in infants and young children, f-Dpd assessment in first
      void single urine samples is an easy, safe, and non-invasive method.

PMID- 10936585
TI  - Transportation of maternal serum specimens for screening for chromosomal
      aneuploidies: effect of seasonal variations, distance, and freezing on the
      stability of the biological markers.
AB  - OBJECTIVES: We studied the stability of maternal serum markers for screening for
      Down syndrome [alpha-fetoprotein (AFP), unconjugated estriol (uE3), total human
      chorionic gonadotropin (hCG), and free beta-human chorionic gonadotropin]
      following transportation. DESIGN AND METHODS: For each gestational week between
      14 and 18 weeks, we collected about 50 samples for each possible combination of
      three potential sources of variation during transportation: season
      (winter/summer), sample frozen/fresh (prior to analysis) and origin (local or
      referred in) for a total of 1845 specimens. Commercial assays were used (IMx,
      Abbott for AFP and total hCG; AutoDelfia and Wallac for free beta-hCG and AFP;
      and radioimmunoassay Ortho-Clinical Diagnostics, for uE3). RESULTS: Results of
      both total and free beta-hCG were significantly higher when samples were
      collected during summer and when they were sent to the laboratory from extramural
      blood drawing sites (multifactorial ANOVA, p < 0. 007). CONCLUSION: We conclude
      that both total and free beta-hCG can be adversely affected during
      transportation. The resulting higher concentrations of these markers may increase
      the false positive rate of prenatal screening programs for aneuploidies.

PMID- 10936586
TI  - Coenzyme Q10 concentrations and antioxidant status in tissues of breast cancer
      patients.
AB  - OBJECTIVES: An increasing amount of experimental and epidemiological evidence
      implicates the involvement of oxygen derived radicals in the pathogenesis of
      cancer development. Oxygen derived radicals are able to cause damage to
      membranes, mitochondria, and macromolecules including proteins, lipids and DNA.
      Accumulation of DNA damages has been suggested to contribute to carcinogenesis.
      It would, therefore, be advantageous to pinpoint the effects of oxygen derived
      radicals in cancer development. DESIGN AND METHODS: In the present study, we
      investigated the relationship between oxidative stress and breast cancer
      development in tissue level. Breast cancer is the most common malignant disease
      in Western women. Twenty-one breast cancer patients, who underwent radical
      mastectomy and diagnosed with infiltrative ductal carcinoma, were used in the
      study. We determined coenzyme Q10 (Q) concentrations, antioxidant enzyme
      activities (mitochondrial and total superoxide dismutase (SOD), glutathione
      peroxidase (GSH-Px), catalase), and malondialdehyde (MDA) levels in tumor and
      surrounding tumor-free tissues. RESULTS: Q concentrations in tumor tissues
      significantly decreased as compared to the surrounding normal tissues (p <
      0.001). Higher MDA levels were observed in tumor tissues than noncancerous
      tissues (p < 0.001). The activities of MnSOD, total SOD, GSH-Px and catalase in
      tumor tissues significantly increased (p < 0.001) compared to the controls.
      CONCLUSIONS: These findings may support that reactive oxygen species increased in
      malignant cells, and may cause overexpression of antioxidant enzymes and the
      consumption of coenzyme Q10. Increased antioxidant enzyme activities may be
      related with the susceptibility of cells to carcinogenic agents and the response
      of tumor cells to the chemotherapeutic agents. Administration of coenzyme Q10 by
      nutrition may induce the protective effect of coenzyme Q10 on breast tissue.

PMID- 10936587
TI  - c-fos and c-jun mRNA expression in a pig liver model of ischemia/reperfusion:
      effect of extended cold storage and the antioxidant idebenone.
AB  - OBJECTIVES: Expression of immediate early genes has been reported during
      reperfusion after ischemia in rat livers due to oxygen radical formation. This
      study investigates in perfused pig livers the effect of the antioxidant idebenone
      and of cold ischemia time on the gene expression of c-fos and c-jun. DESIGN AND
      METHODS: Livers were perfused for 210 min after 0.5 h or 20 h ischemic storage (4
      degrees C). One group of pigs was fed idebenone (280 mg/day/7days) prior to organ
      harvesting. C-fos and c-jun mRNA were determined by RT-PCR at 3, 30, 60, 120 180,
      210 min during reperfusion. RESULTS: Lipid peroxidation increased in liver tissue
      form 0.54 +/- 0.21 to 1. 09 +/- 0.54 nmol MDA/mg protein during reperfusion after
      20 h compared to 0.5 h cold storage. This was antagonized by idebenone (0. 68 +/-
      0.20 nmol/MDA/mg protein). C-fos and c-jun were strongly induced in livers stored
      for 20 h, which was attenuated by idebenone (p < 0.05). CONCLUSIONS: These
      findings suggest that cold ischemia time and oxygen radicals are critical for
      immediate early gene expression and that application of an effective antioxidant
      can attenuate this early stress reaction of the pig liver.

PMID- 10936588
TI  - Genetic variations of the hepatic lipase gene in Korean patients with coronary
      artery disease.
AB  - OBJECTIVES: To investigate the association between the HL gene (LIPC)
      polymorphism, plasma lipid levels and coronary artery disease (CAD). DESIGN AND
      METHODS: One hundred thirty-seven subjects with CAD and 124 age-matched controls
      were examined by polymerase chain reaction (PCR). The PCR products were analyzed
      for LIPC genotyping by enzyme digestion. RESULTS: The allele frequencies of the
      three polymorphisms in the LIPC gene were not significantly different between the
      controls and CAD patients. The + allele of the -514 promoter polymorphism was
      associated with higher total cholesterol (p = 0.05), apolipoprotein (apo) AI (p =
      0.04) levels in the men of the normal group, and the apoB level (p = 0.03) in the
      women of the CAD group without allele effect. The allele frequencies of the -250
      and -514 promoter polymorphisms of Koreans were significantly different from
      those of the white and African American populations studied (p < 0.05).
      CONCLUSIONS: The -514 promoter polymorphism may fluctuate on the lipid levels due
      to linkage disequilibria with other polymorphisms of the LIPC gene or nearby
      genes. The difference of the -250 promoter allele frequencies among the different
      populations may partially explain the variation of the HDL levels in ethnic
      groups. To elucidate the more exact associations of LIPC polymorphism with the
      plasma lipid levels, the precise biochemical mechanisms of the LIPC alleles are
      required.

PMID- 10936589
TI  - Utility of alpha-glutathione S-transferase assessment in chronic hepatitis C
      patients with near normal alanine aminotransferase levels.
AB  - OBJECTIVES: To study whether determining alpha-glutathione S-transferase (alpha
      GST) might improve the assessment of chronic hepatitis C (CHC) patients with near
      normal alanine aminotransferase levels (NNA). DESIGN AND METHODS: We studied 119
      viraemic CHC patients. They were subdivided into two groups according to the
      pattern of alanine aminotransferase (ALT) alteration, i.e. consistently above
      (HA) or below (NNA) twice the upper normal value. In these patients we assessed
      alpha-GST and correlated its levels to clinical, histological, and virological
      findings, further evaluating whether alpha-GST might improve the assessment of
      CHC patients with NNA. RESULTS: alpha-GST showed a significant correlation with
      aminotransferases, though not with histological necroinflammatory activity and
      fibrosis or with hepatitis C virus RNA levels. Twenty-seven patients had NNA
      (23%), and within this subgroup of patients alpha-GST identified a subset of
      patients with a higher viral load. CONCLUSIONS: alpha-GST in CHC patients is
      related to hepatocellular necrosis parameters, but unrelated both to histology
      and to viraemia. However, in patients with NNA, alpha-GST identified a subgroup
      of patients with a higher viral load. In this subgroup of patients alpha-GST
      alteration likely represents the expression of a more severe damage. Because this
      injury is not detectable by the usual biochemical or histological work-up, we
      suggest that alpha-GST could a useful tool for monitoring liver damage over time.

PMID- 10936590
TI  - Relation between lipoprotein (a) and in vitro oxidation of apolipoprotein B
      containing lipoproteins.
AB  - OBJECTIVES: To assess the relationship between lipoprotein (a) [Lp (a)] and
      lipoprotein oxidation in patients with coronary artery disease (CAD). DESIGN AND
      METHODS: Oxidation of apolipoprotein (apo)B-containing lipoproteins, vitamin E,
      carotenoids, lipid-lipoprotein levels were determined in 171 CAD and 70 non-CAD
      subjects. RESULTS: In CAD patients with Lp (a) concentrations >/= 30 mg/dL; total
      cholesterol (TC), low density lipoprotein cholesterol (LDL-C), malondialdehyde
      (MDA), and apo B levels were significantly higher and lag-time and age were
      significantly lower than those of CAD patients with Lp (a) concentrations < 30
      mg/dL. In non-CAD subjects with Lp (a) concentrations >/= 30 mg/dL; TC, LDL-C,
      and vitamin E levels were significantly higher and lag-time was significantly
      lower than those of non-CAD subjects with Lp (a) concentrations < 30 mg/dL. In
      CAD patients, Lp (a) correlated negatively with lag-time and positively with MDA
      levels. Lp (a) correlated negatively with lag-time and vitamin E levels in non
      CAD subjects. CONCLUSIONS: We have shown that plasma apo B-containing
      lipoproteins of both CAD and non-CAD subjects with Lp (a) levels >/= 30 mg/dL are
      more susceptible to in vitro oxidative modification than those of subjects with
      Lp (a) levels < 30 mg/dL. The relationship between Lp (a) and enhanced
      susceptibility of apo B-containing lipoproteins to oxidation, appears to support
      routine investigation of Lp (a).

PMID- 10936591
TI  - A case of beta thalassemia major detected using HPLC in a child of Chinese
      ancestry.

PMID- 10936592
TI  - Serum c-erb B2 oncoprotein levels are elevated in recurrent and metastatic breast
      cancer.

PMID- 10936593
TI  - Evaluation of the Abbott PCx (R) point of care glucose analyzer in a pediatric
      hospital.

PMID- 10936594
TI  - Improved method for direct DNA sequencing of the human lipoprotein lipase gene
      using an auto DNA sequencer.

PMID- 10936596
TI  - Postural breathing pattern changes in patients with myotonic dystrophy.
AB  - We recorded by pneumotachography the breathing in nine patients with myotonic
      dystrophy (MD), both seated and supine and with eyes open in both positions.
      Irregular breathing (coefficient of variation >20% for VT and TTOT) was observed
      in six of the patients, two of whom showed irregularity in both positions whilst
      the remaining four had irregular breathing only when supine. In addition, in this
      latter group, irregularities first appeared in VT and only after a few minutes in
      TTOT. Whereas in the group exhibiting irregular breathing in both seated and
      supine positions, irregularities were observed throughout the recording. However,
      no significant difference in any ventilatory variable was observed as between the
      two postures. Rib cage (RC) and abdomen (AB) motions were recorded by
      uncalibrated respiratory inductance plethysmography. Although for MD patients the
      mean values of the RC/AB ratio lay within the normal range the relative decrease
      in value as between seated (0.78+/-0.52) and supine (0.31+/-0.13) position was
      less than in healthy subjects. These observations suggest that MD may cause
      deficiencies in several mechanisms. Analyses of the respiratory pattern in each
      patient may provide information leading to the identification of the impaired
      respiratory mechanisms.

PMID- 10936595
TI  - Measurements of circulating ionized magnesium level: fresh whole blood samples
      versus serum samples.

PMID- 10936598
TI  - Segmental responses of abdominal motoneurons in decerebrate cats.
AB  - As a first step towards elucidating the synaptic organization underlying
      segmental responses of abdominal muscles I recorded the responses of branches of
      the left cranial (L(1)L) and caudal (L(2)L) and right caudal (L(2)R) lumbar
      (iliohypogastric) nerves to electrical shocks of different intensities to the
      caudal branch of L(2)L in nine decerebrate paralyzed and ventilated cats. If such
      reflex responses subserve a respiratory function, then they should be bilaterally
      similar; if they do not, lateral asymmetry should be evident. At intensities
      activating only large diameter axons (i.e. spindle and tendon organ afferents),
      stimulation typically elicited in the rostral branch of L(2)L a brief
      (approximately 1.6 ms) short-latency (approximately 1.8 ms) excitation followed
      by a suppression of activity (approximately 8-26 ms). Responses increased in
      amplitude as stimulus intensity increased, the suppression of activity being
      interrupted by an excitation (latency approximately 5. 4 ms, duration
      approximately 3.6 ms) in four cats. L(1)L responses were similar. Contralateral
      responses in the same segment (L(2)R) in five cats consisted of a suppression of
      activity in four, a short-latency (approximately 3.3 ms) excitation being present
      in three; increases in stimulus intensity in two additional cats elicited these
      excitatory and inhibitory responses. I conclude: (1) the variable responses
      between cats reflect differences in nerve bundles and, therefore, target muscles,
      from which the recordings were made; and (2) because of the lateral asymmetry of
      responses, abdominal afferent activation elicited postural (rotational) rather
      than respiratory reflexes.

PMID- 10936597
TI  - P(O(2))-P(CO(2)) stimulus interaction in [Ca(2+)](i) and CSN activity in the
      adult rat carotid body.
AB  - Since glomus cell intracellular calcium ([Ca(2+)](i)) plays a key role in
      generating carotid sinus nerve (CSN) discharge, we hypothesized that glomus cell
      [Ca(2+)](i) would correspond to CSN discharge rates during P(O(2))-P(CO(2))
      stimulus interaction in adult rat carotid body (CB). Accordingly, we measured
      steady state P(O(2))-P(CO(2)) interaction in CSN discharge rates during
      hypocapnia (P(CO(2))=8-10 Torr), normocapnia (P(CO(2))=33-35 Torr) and
      hypercapnia (P(CO(2))=68-70 Torr) in normoxia (P(O(2)) approximately 130 Torr)
      and hypoxia (P(O(2)) approximately 36 Torr). The results showed P(O(2))-P(CO(2))
      stimulus interaction in CSN responses. [Ca(2+)](i) levels were measured in
      isolated type I cells (2-3 cells/field), using Ca(2+) sensitive fluoroprobe indo
      1AM. The [Ca(2+)](i) responses increased with increasing P(CO(2)) in normoxia. In
      hypoxia, [Ca(2+)](i) did not increase during hypocapnia but increased during
      normocapnia, showing P(O(2))-P(CO(2)) interaction. However, CSN response during
      hypoxia was far greater than that for [Ca(2+)](i) response, particularly during
      hypocapnic hypoxia. Thus, the [Ca(2+)](i) interaction cannot account for the
      whole CSN interaction. The origin of this CSN P(O(2)-)P(CO(2)) interaction must
      have occurred in part beyond cellular [Ca(2+)](i) interaction. Interactions at
      both sites (glomus cell membrane and sinus nerve endings) are reminiscent of
      reversible O(2)-heme protein reaction with a Bohr effect.

PMID- 10936599
TI  - Ventilatory responses to hypercapnia and hypoxia following chronic hypercapnia in
      the rat.
AB  - This study investigated the effects of an 18 week exposure to 10% CO(2) in air on
      minute ventilation (V(E)), breathing pattern and the chemoresponiveness of rats
      to hypoxic and hyperoxic stimuli. We found that V(E) remained elevated over the
      18 weeks. Nonetheless, the breathing pattern changed significantly. Tidal volume
      increased and the durations of inspiration and the total cycle decreased. After
      the sustained hypercapnia the mean Pa(CO(2)) was 72.0+/-5.1 (S. D.) mmHg. Every 6
      weeks the chemoresponiveness of the CO(2)-exposed rats was tested by an acute
      exposure sequentially to room air, then a 6% O(2), 10% CO(2) and 84% N(2) gas
      mixture, and finally a 90% O(2) in 10% CO(2) mixture. On either room air or the
      hyperoxic-hypercapnic mixture V(E) fell to its pre-hypercapnic level. On the
      hypoxic-hypercapnic mixture V(E) increased significantly. These results
      demonstrate that the initial stimulating effect of 10% CO(2) on V(E) persisted
      for the entire 18 weeks without altering hypoxic or hyperoxic ventilatory
      responses.

PMID- 10936601
TI  - Hypoxic depression of circadian oscillations in sino-aortic denervated rats.
AB  - We hypothesized that hypoxia depresses the circadian oscillations of body
      temperature (T(b)) and oxygen consumption (V(O(2))) even in the absence of inputs
      from the peripheral chemoreceptors. Adult rats were sino-aortic denervated
      bilaterally (SAX, N=17) or sham-operated (Sham, N=17). Ten rats of each group
      were instrumented for measurements of T(b) and activity by telemetry. Animals
      were exposed to normoxia (21% O(2)), hypoxia (10.5% O(2)), and again normoxia,
      each for a 5-day duration, in constant light ('free-running') conditions. Hypoxia
      almost eliminated the T(b) circadian oscillations, mostly by abolishing the daily
      rise in T(b). Upon return to normoxia T(b) rapidly increased and the normal
      oscillation was reestablished at the expected phase of the cycle. The hypoxic
      effects did not differ between Sham and SAX. During hypoxia the amplitude of the
      circadian oscillation of activity was reduced by approximately 25%, and that of
      V(O(2)), measured by an open flow method in the remaining Sham and SAX rats (N=7
      each), was reduced by almost 50%. In all cases there was no difference between
      the two groups. We conclude that activation of the peripheral chemoreceptors is
      not required for the manifestation of the hypoxic depression of the metabolic and
      temperature circadian oscillations. The results are compatible with the view that
      hypoxia depresses thermogenesis acting on the thermoregulatory centers of the
      hypothalamus.

PMID- 10936600
TI  - Acute partial paralysis alters perceptions of air hunger, work and effort at
      constant P(CO(2)) and V(E).
AB  - Breathing sensations of AIR HUNGER, WORK and EFFORT may depend on projections of
      central motor discharge (corollary discharge) to the forebrain. Source of motor
      drive (brainstem or cortex) may determine what is perceived. To test the effect
      of changing motor discharge at constant ventilation, we induced partial
      neuromuscular blockade during hypercapnic hyperpnea (31 + or - 9 L min(-1);
      PET(CO(2))=49 + or - 2 Torr) and during matched volitional hyperpnea (34 + or - 5
      L min(-1); PET(CO(2))=41 + or - 1 Torr). Decline of vital capacity was similar
      between conditions (39%). Ventilation was unchanged with paralysis, indicating
      increased respiratory motor drive to maintain hyperpnea. Sensations were rated on
      a seven point ordinal scale. Median EFFORT and WORK increased 3-3.5 points with
      paralysis during both forms of hyperpnea (P<0.02, Wilcoxon signed rank). Median
      AIR HUNGER increased 2.5 points with paralysis during hypercapnic (P<0.02) but
      not during volitional hyperpnea. Data suggests that EFFORT and WORK arise from
      motor cortex activity (subjects reported engaging volitional control when
      paralyzed even during hypercapnia) and suggests that AIR HUNGER arises from
      medullary motor activity.

PMID- 10936603
TI  - Cretaceous (Late Albian) coniferales of Alexander Island, Antarctica. 1: Wood
      taxonomy: a quantitative approach.
AB  - Silicified conifer woods are very common in the mid-Cretaceous (Late Albian,
      100Ma) Triton Point Member of the Neptune Glacier Formation (Fossil Bluff Group),
      SE Alexander Island, Antarctica. These occur as up to 7m high in situ tree trunks
      and stumps rooted in carbonaceous palaeosols and as allochthonous logs and wood
      fragments in fluvial channel and sheet sandstone facies. Sixty-eight wood samples
      were examined in this study and were classified in terms of five form taxa using
      a quantitative approach. Araucarioxylon (1.5% of specimens) is characterised by
      dominantly multiseriate, alternately arranged bordered pitting on radial tracheid
      walls and by 1-4 araucarioid cross-field pitting. Araucariopitys (11.8% of
      specimens) is characterised by dominantly uniseriate tracheid pitting with
      subordinate biseriate, alternate tracheid pitting and by 1-4 araucarioid cross
      field pitting. Podocarpoxylon sp. 1 (63.1% of specimens) is characterised by
      contiguous, uniseriate tracheid pitting and 1-2 podocarpoid cross-field pits.
      Podocarpoxylon sp. 2 (22.1% of specimens) is similar to P. sp. 1, differing only
      in that ray height is lower, tracheid pits are dominantly spaced more than one
      pit diameter apart and abundant axial parenchyma is present. These first four
      taxa all possess growth rings with subtle boundaries. Taxodioxylon (1.5% of
      specimens) is characterised by 1-2 seriate, oppositely arranged, bordered
      tracheid pitting, 1-2 taxodioid cross-field pitting and very marked ring
      boundaries. These woods were derived from large trees with basal stump diameters
      of up to 0.5m and probable heights of up to 29m. Data from leaf traces suggest
      that Araucariopitys and Podocarpoxylon sp. 1 and sp. 2 (97% of specimens) were
      evergreen with leaf retention times of >5years. These predominantly evergreen
      conifer forests grew in a mild, high latitude (75 degrees S) environment during
      the mid-Cretaceous greenhouse climate phase.

PMID- 10936602
TI  - Quantification of diffusion distance within the spongy myocardium of hearts from
      antarctic fishes.
AB  - We developed a stereological method for quantifying diffusion distance within
      spongy myocardium. Using this method we compared the hearts of three species of
      Antarctic fishes that vary in expression of oxygen-binding proteins. We examined
      hearts from Gobionotothen gibberifrons, a red-blooded species whose ventricle has
      myoglobin (Mb), and hearts of two species of icefish that lack hemoglobin (Hb)
      and vary in expression of cardiac Mb; Chionodraco rastrospinosus expresses Mb,
      Chaenocephalus aceratus does not. Average diffusion distance within ventricular
      tissue is greater in red-blooded Antarctic teleosts (9.82 + or - 1.37 microm)
      compared with icefish (C. rastrospinosus, 6.20 microm + or - 0.86; C. aceratus,
      6.23 + or - 0.41 microm). Average diffusion distance to a mitochondrion parallels
      this trend because mitochondria are uniformly distributed within cardiac muscle.
      Results show that loss of Hb is correlated with increased trabeculation of heart
      ventricle. Loss of Mb however, is not correlated with an increase in
      trabeculation of ventricular tissue, despite significant differences in cellular
      ultrastructure compared with species that express the protein.

PMID- 10936604
TI  - Impact of forest disturbance on the pollen influx in lake sediments during the
      last century.
AB  - The pollen accumulation rates of four lakes in different regions of Estonia were
      estimated in order to study the relationship between pollen influx and the
      character and intensity of disturbances in the pollen catchment area. The pollen
      influx data obtained are in accordance with model calculations on the size of the
      pollen source areas. The influx of arboreal pollen and that of the dominant taxa
      (mainly Pinus) in the lakes investigated shows that, in the case of small lakes
      (area 3-6ha) in a forested landscapes, the bulk of the pollen originates from an
      area within 100-200m around the lake. The distribution patterns of influx from
      two lakes situated close to each other but at different distances from forest
      fires show that past disturbances can be reliably detected when the disturbance
      occurred in the immediate vicinity of the lake and at least 25% of the local
      pollen source area was involved. In the case of a large lake (137ha) only fires
      embracing thousands of hectares can be detected in the pollen diagrams.

PMID- 10936605
TI  - Aspects of Romanian Early Jurassic palaeobotany and palynology. Part II. A new
      species of Pachypteris from Cristian.
AB  - The Lower Jurassic (Sinemurian) deposits of Cristian (Brasov County, Romania)
      contain a well-preserved land flora. Pachypteris gradinarui n.sp., a new species
      of seed fern foliage belonging to the Corystospermales, is described, figured and
      analysed. The species has a bipinnate, petioled frond; secondary rachises
      inserted on the upper side of the primary rachis; rounded, occasionally lobed
      pinnules without marked abaxial thickening or folding. The material is compared
      with other Pachypteris species, and with Cycadopteris, a related genus
      characterised by marginal (cuticular) thickening and folding, as it presents
      transitional characters between the two genera.

PMID- 10936606
TI  - A new species of Nehvizdya (Ginkgoales) from the Lower Cretaceous of the Iberian
      Ranges (Spain).
AB  - A new species of the formerly monospecific genus Nehvizdya Hlustik, Nehvizdya
      penalveri sp. nov. is described from the Albian of the Escucha Formation (Eastern
      Iberian Ranges, Teruel, Spain). The type species Nehvizdya obtusa Hlustik was
      first found in the Lower-Middle Cenomanian Peruc Member of the Peruc-Korycany
      Formation (Bohemian Massif, Czech Republic). Both taxa closely resemble each
      other, not only in leaf shape and venation pattern, but also in their epidermal
      structures and the occurrence of resin bodies. The Spanish species, however, is
      notable for its marked amphistomatic leaves with stomatal apparatus, which have
      inner folds inside the stomatal pits. Comparison with Eretmophyllum andegavense
      Pons et al. from the Cenomanian of the Baugeois Clays (Maine-et-Loire, France)
      allows us to transfer this species to the genus Nehvizdya Hlustik. The new
      combination proposed is Nehvizdya andegavense (Pons et al.) comb. nov. A
      taphonomic analysis in this layer appears to characterise a biocoenosis formed
      from N. penalveri sp. nov. and Frenelopsis alata (K. Feistmantel) Knoblock.
      Similar associations have been described in the Czech and French Cenomanian. In
      all three cases, the associations grew around coastal lagoons and ponds where
      they formed a shrubby halophyte vegetation.

PMID- 10936607
TI  - Charbeckia macrophylla gen. et sp. nov. from the Lower Mississippian Price
      (Pocono) Formation of southeastern West Virginia.
AB  - A fossil plant discovery from the Price (Pocono) Formation of southeastern West
      Virginia provides new information on the poorly known compression floras of the
      Lower Mississippian of North America. The new plant described herein consists of
      long tapering bipinnate fronds with imbricate basal pinnae, planate apical
      pinnae, and unlobed, elliptical to obovate pinnules with open dichotomous
      venation. Veins concentrated in the medial region of the pinnule curve toward the
      lateral margin, suggestive of an early stage in the evolution of a midrib.
      Pinnules exhibit a distinctly revolute or otherwise reinforced margin. The
      exceptional length of some fronds (over 1m) and pinnule size (some over 3cm by
      2cm) strongly contrast with the generally diffusely branched fronds and small or
      highly dissected pinnule morphology that typify Early Mississippian leaf taxa. A
      new generic assignment, Charbeckia macrophylla, is thereby justified. The rigid
      appearance of the tapering rachis, the imbricate pinnae that appear to have
      resisted compression, and the reinforced pinnule margins imply thick evergreen
      leaves, perhaps adapted for drought tolerance. A possible Calamopityalean
      affinity is indicated by the size of the fronds and the stout petioles, which
      fall within the expected size range of the Kalymma-type petiole bases described
      from the nearby New Albany Shale of Tournaisian age.

PMID- 10936608
TI  - Fruits of Tetrapterys (Malpighiaceae) from the Oligocene of Hungary and Slovenia.
AB  - Propeller-like winged fruits of Tetrapterys harpyiarum Unger from the Oligocene
      of Sotzka, Budapest, Eger-Vecsey valley, and a new occurrence at Eger-Kiseged,
      were reinvestigated and compared in detail with extant species of Tetrapterys
      (Malpighiaceae) and with other dicotyledonous genera with four winged fruits. T.
      harpyiarum fruits are bilaterally symmetrical, consisting of a globose nut
      surrounded by four elongate wings with parallel venation. Tetrapterys is now
      distributed only in tropical America and this implies that there was an
      opportunity for Tetrapterys to spread between the Partethys region and the New
      World during the Tertiary.

PMID- 10936609
TI  - An unusual process structure in Tresarcus, a new acritarch genus from the
      Ordovician of Oland, Sweden.
AB  - Tresarcus, a new monospecific acritarch genus, is established along with the type
      species Tresarcus suecicus sp. nov. It was found in samples from the upper Arenig
      (Lenodus sp. A conodont Zone) of the Hagudden and Horns Udde sections, Oland,
      Sweden. The three-arched process tip is a peculiar characteristic of Tresarcus.
      This structure recalls, from a morphological point of view (though at a different
      dimensional scale), the four-arched termination of the epidermal hairs that
      ornate the adaxial (upper) surface of the assimilating leaves of Salvinia natans,
      Adanson, 1785 (Pteridophyta). This species has an aquatic habit and the four
      arched structure as the tip of the epidermal is interpreted as a device that
      favours buoyancy by trapping air on the leaf surface. A similar function is
      hypothesized for the three-arched processes of Tresarcus.

PMID- 10936610
TI  - Late Silurian trilete spores from northern Jiangsu, China.
AB  - The Late Silurian is generally considered to a particular significant key period
      in the study of early land vascular plants. A trilete spore assemblage of the
      Upper Silurian is described from northern Jiangsu, China. This assemblage
      comprises 11 genera and 20 species of trilete spores (including laevigate,
      apiculate, perinotrilite, patinate, rarely distally murornate and equatorially
      crassitate, and three indeterminate trilete miospores forms). It has similarities
      to those described from coeval assemblages from around the world (e.g., England
      and South Wales; Tripolitania, Libya; Cornwallis Island, Canadian Arctic;
      Northwest Spain). The rare cryptospore, only one specimen (Tetrahedraletes sp.)
      had been found to be associated with the Chinese trilete spore assemblage. The
      discovery of the trilete spores from Late Silurian rocks indicates the existence
      of early land plants, some possibly vascular, at that time in northern Jiangsu,
      China.

PMID- 10936611
TI  - The fossil record of Cunoniaceae: new evidence from Late Cretaceous wood of
      Antarctica?
AB  - Fossil angiosperm wood from Upper Cretaceous sediments of Livingston Island and
      James Ross Island in the northern Antarctic Peninsula region is identified as
      having the combination of anatomical characters most similar to modern
      Cunoniaceae. The material is characterised by predominantly solitary vessels,
      opposite to scalariform intervessel pitting, scalariform perforation plates,
      heterocellular multiseriate and homocellular uniseriate rays, diffuse axial
      parenchyma. Anatomically, the specimens conform most closely to the fossil organ
      genus Weinmannioxylon Petriella which has been placed within the Cunoniaceae. The
      presence of Weinmannioxylon in Late Cretaceous sediments suggests that taxa
      within or stem taxa to the Cunoniaceae might have been a notable component of the
      forest vegetation that covered the Antarctic Peninsula during the Late Mesozoic
      and may therefore represent the earliest record of this family.

PMID- 10936613
TI  - Immunochemical analyses of estrogen receptors in human breast tumors by a novel
      monoclonal estrogen receptor antibody (EVG F9).
AB  - The objective of this study was to assess the potential utility of a new site
      directed, monoclonal anti-estrogen receptor antibody (EVG F9) in detection and
      analyses of human breast tumor estrogen receptor (ERalpha), using immunoblotting
      and immunohistochemical assays. Using Western Blot analyses, we demonstrated that
      EVG F9 monoclonal antibody binds specifically to ERalpha and does not cross-react
      with ERbeta. Furthermore, binding of EVG F9 to ERalpha was effectively displaced
      with the immunogenic peptide in Western Blots and in immunohistochemical
      analyses. In Western Blot analyses, EVG F9 detected ERalpha at low concentrations
      approaching 5 to 10 fmol/sample. Determination of ERalpha status of a series of
      human breast tumor samples by Western Blot analyses or immunohistochemistry using
      EVG F9 correlated well with ERalpha values measured by ligand binding assays.
      These observations suggest that EVG F9 monoclonal anti-ERalpha antibody is a
      valuable immunochemical tool for detection and analyses of ERalpha in human
      breast tumors.

PMID- 10936612
TI  - Selective activation of liver X receptor alpha by 6alpha-hydroxy bile acids and
      analogs.
AB  - We have found that certain natural 6alpha-hydroxylated bile acids are receptor
      specific activators of nuclear liver X receptor alpha (LXRalpha) (NR1H3), a
      nuclear receptor regulating the expression of the cholesterol 7alpha-hydroxylase
      gene, coding for the rate-limiting enzyme in the major pathway of bile acid
      synthesis. The LXR homolog, ubiquitous nuclear receptor (UR/LXRbeta) (NR1H2), was
      also activated by these bile acids, but at higher concentrations than for
      LXRalpha. Synthetic 6alpha-hydroxylated bile acid analogs were synthesized with
      LXRalpha-selective agonistic activity, with potential to modulate cholesterol
      catabolism in hypercholesterolemia.

PMID- 10936614
TI  - Synthesis of enterolactone and enterodiol precursors as potential inhibitors of
      human estrogen synthetase (aromatase).
AB  - A series of variably substituted derivatives of lignan lactones and diols were
      prepared using tandem conjugate addition reaction as a key step. These
      theoretical precursors of the mammalian lignans enterolactone 1 and enterodiol 3
      are moderate or weak inhibitors of human aromatase activity.

PMID- 10936615
TI  - Synthesis of 6-oxy functionalized campest-4-en-3-ones: efficient
      hydroperoxidation at C-6 of campest-5-en-3-one with molecular oxygen and silica
      gel.
AB  - As a reference compound library for the investigation of biosynthesis of
      brassinosteroids, focused on a pathway from campesterol (1) to campestanol (2), 6
      oxy functionalized campest-4-en-3-ones as well as campest-5-en-3-one (7) and
      campestane-3,6-dione were prepared from 1. Oxidation of 1 with pyridinium
      chlorochromate buffered by calcium carbonate gave 5-en-3-one (7) in 76% yield.
      Treatment of 7 with silica gel under an oxygen atmosphere in ethyl ether at room
      temperature produced efficient hydroperoxidation at the C-6 position to give
      6alpha-hydroperoxycampest-4-en-3-one and 6beta-hydroperoxycampest-4-en-3-one in
      34% and 49% yields, respectively. These compounds were converted to 6alpha
      hydroxycampest-4-en-3-one and 6beta-hydroxycampest-4-en-3-one by reduction with
      triethyl phosphite. This provided the first example of the practical use of
      hydroperoxidation at C-6 of a Delta(5(6))-unsaturated 3-oxo-steroid with
      molecular oxygen and silica gel. On the other hand, oxidation of 1 with
      pyridinium chlorochromate in the absence of calcium carbonate gave campest-4-ene
      3,6-dione in 64% yield. This compound was then converted in a highly
      stereoselective manner to campestane-3,6-dione with A/B trans ring junction by
      reduction with titanium (III) chloride in 85% yield.

PMID- 10936616
TI  - Immunochemical studies on the putative plasmalemmal receptor for 1, 25
      dihydroxyvitamin D(3). III. Vitamin D status.
AB  - The effect of vitamin D status on levels of the putative 1, 25(OH)(2)D(3)
      membrane receptor (pmVDR) was studied in chick intestine, kidney, and brain.
      Western analyses and assays for specific [(3)H]1,25(OH)(2)D(3) binding indicated
      that, in intestine, pmVDR levels were greatest in -D chicks relative to +1,25D
      and +D animals (P < 0.05). In kidney, protein levels and specific binding
      followed the order +D > +1,25D, -D. In brain, vitamin D status did not affect
      protein levels or specific binding levels. In tissue from normal chicks, both
      protein and specific binding followed the order of intestine > kidney > brain
      membranes. Intestinal cells were further evaluated for the effect of
      1,25(OH)(2)D(3) on selected "rapid responses." Extrusion of (45)Ca in response to
      130 pM 1, 25(OH)(2)D(3) in vitro was greater in cells from -D chicks than from
      +1,25D or normal birds. Analyses of signal transduction events revealed
      diminished hormone-induced intracellular calcium oscillations (as assessed by
      fura-2 fluorescence), and lack of steroid-enhanced protein kinase (PK) A activity
      in intestinal epithelial cells from -D chicks relative to +D chicks. PK C
      activation by 130 pM 1,25(OH)(2)D(3) was approximately twofold in cells from +D
      or -D chicks. The combined results indicate that vitamin D status differentially
      affects the pmVDR in intestine, kidney, and brain. In intestine, vitamin D
      deficiency differentially affects (45)Ca handling, intracellular calcium
      oscillations, PK A and PK C activities in response to 1,25(OH)(2)D(3).

PMID- 10936618
TI  - Editor's foreword

PMID- 10936617
TI  - Synthesis of (5-azido-2-nitrobenzoyl)amido, (4-azido-2-nitrophenyl)amino, and (5
      azido-2-nitro-3,4, 6-trifluorophenyl)amino derivatives of 17alpha-methylamino-,
      17alpha-ethylamino-, and 17alpha-propylamino-5alpha-dihydrotestosterone as
      reagents of different linker lengths for the photoaffinity labeling of sex
      hormone binding globulins and androgen receptors.
AB  - The photoactivable aryl azide reagents, N-(5-azido-2-nitrobenzoyl)oxysuccinimide,
      4-azido-1-fluoro-2-nitrobenzene, and 4-azido-1-nitro-2,4,5, 6-tetrafluorobenzene
      have been condensed at the extremity of three 17alpha-aminomethyl, 17alpha
      aminoethyl, and 17alpha-aminopropyl side-chains introduced on (17S)-spiro-(3, 3
      dimethoxy)-5alpha-androstan-17beta,2'-oxirane either directly, by ammonolysis, in
      the first case, or by conversion to nitrile intermediates with cyano or
      cyanomethyl anions and subsequent reduction to amines with lithium aluminum
      hydride, in the two other cases. The 3,3-dimethoxy group of these photoreagents
      was cleaved by acidolysis to a 3-ketone, which was reduced with sodium
      borohydride to a 3beta-alcohol. All of these compounds were characterized by (1)H
      and (13)C-NMR as well as by (1)H, (13)C heteronuclear 2D NMR, which helped to
      resolve ambiguous assignments. Significant differences of substituent-induced
      effects on (13)C NMR signals were observed according to the 17alpha-side-chain
      length, the structure of the terminal aryl azide groups, and the solvent, showing
      a different behavior of N-5-azido-2-nitrobenzoyl derivatives as compared with 4
      azido-2-nitrophenylamino and 5-azido-2-nitro-3,4, 6-trifluorophenylamino
      derivatives. The N-5-azido-2-nitrobenzoyl conjugates of the three 17alpha
      aminomethyl, aminoethyl, and aminopropyl derivatives of 5alpha
      dihydrotestosterone were tested as ligands for purified human sex hormone-binding
      globulin and for the cytosolic androgen receptor of rat ventral prostate by
      competition experiments with tritiated 5alpha-dihydrotestosterone. The increasing
      lengths of the aminomethyl, aminoethyl, and aminopropyl spacer arms of N-5-azido
      2-nitrobenzoyl conjugates were found to correspond to decreasing relative binding
      affinities for sex hormone-binding globulin (0.76, 0.47, and 0.10, respectively,
      versus 1.00 for 5alpha-dihydrotestosterone) while only the longer aminoethyl and
      aminopropyl conjugates interacted significantly with the androgen receptors (0.05
      and 0.10, respectively).

PMID- 10936619
TI  - Conotoxins, in retrospect.

PMID- 10936620
TI  - Twenty years of dendrotoxins.
AB  - Dendrotoxins are small proteins that were isolated 20 years ago from mamba
      (Dendroaspis) snake venoms (Harvey, A.L., Karlsson, E., 1980. Dendrotoxin from
      the venom of the green mamba, Dendroaspis angusticeps: a neurotoxin that enhances
      acetylcholine release at neuromuscular junctions. Naunyn-Schmiedebergs Arch.
      Pharmacol. 312, 1-6.). Subsequently, a family of related proteins was found in
      mamba venoms and shown to be homologous to Kunitz-type serine protease
      inhibitors, such as aprotinin. The dendrotoxins contain 57-60 amino acid residues
      cross-linked by three disulphide bridges. The dendrotoxins have little or no anti
      protease activity, but they were demonstrated to block particular subtypes of
      voltage-dependent potassium channels in neurons. Studies with cloned K(+)
      channels indicate that alpha-dendrotoxin from green mamba Dendroaspis angusticeps
      blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nanomolar range, whereas toxin K
      from the black mamba Dendroaspis polylepis preferentially blocks Kv1.1 channels.
      Structural analogues of dendrotoxins have helped to define the molecular
      recognition properties of different types of K(+) channels, and radiolabelled
      dendrotoxins have also been useful in helping to discover toxins from other
      sources that bind to K(+) channels. Because dendrotoxins are useful markers of
      subtypes of K(+) channels in vivo, dendrotoxins have become widely used as probes
      for studying the function of K(+) channels in physiology and pathophysiology.

PMID- 10936622
TI  - The cystine knot motif in toxins and implications for drug design.
AB  - The cystine knot structural motif is present in peptides and proteins from a
      variety of species, including fungi, plants, marine molluscs, insects and
      spiders. It comprises an embedded ring formed by two disulfide bonds and their
      connecting backbone segments which is threaded by a third disulfide bond. It is
      invariably associated with nearby beta-sheet structure and appears to be a highly
      efficient motif for structure stabilization. Because of this stability it makes
      an ideal framework for molecular engineering applications. In this review we
      summarize the main structural features of the cystine knot motif, focussing on
      toxin molecules containing either the inhibitor cystine knot or the cyclic
      cystine knot. Peptides containing these motifs are 26-48 residues long and
      include ion channel blockers, haemolytic agents, as well as molecules having
      antiviral and antibacterial activities. The stability of peptide toxins
      containing the cystine knot motif, their range of bioactivities and their unique
      structural scaffold can be harnessed for molecular engineering applications and
      in drug design. Applications of cystine knot molecules for the treatment of pain,
      and their potential use in antiviral and antibacterial applications are
      described.

PMID- 10936623
TI  - Endogenous neurotoxins from tryptophan.
AB  - In most tissues, including brain, a major proportion of the tryptophan which is
      not used for protein synthesis is metabolised along the kynurenine pathway. Long
      regarded as the route by which many mammals generate adequate amounts of the
      essential co-factor nicotinamide adenine dinucleotide, two components of the
      pathway are now known to have marked effects on neurones. Quinolinic acid is an
      agonist at the N-methyl-D-aspartate sensitive subtype of glutamate receptors in
      the brain, while kynurenic acid is an antagonist and, thus, a potential
      neuroprotectant. A third kynurenine, 3-hydroxykynurenine, is involved in the
      generation of free radicals which can also damage neurones. Quinolinic acid is
      increasingly implicated in neurodegenerative disorders, most especially the AIDS
      dementia complex and Huntington's disease, while kynurenic acid has become a
      standard for the identification of glutamate-releasing synapses, and has been
      used as the parent for several groups of compounds now being developed as drugs
      for the treatment of epilepsy and stroke.

PMID- 10936621
TI  - Tetanus and botulinum neurotoxins: turning bad guys into good by research.
AB  - The neuroparalytic syndromes of tetanus and botulism are caused by neurotoxins
      produced by bacteria of the genus Clostridium. They are 150 kDa proteins
      consisting of three-domains, endowed with different functions: neurospecific
      binding, membrane translocation and specific proteolysis of three key components
      of the neuroexocytosis apparatus. After binding to the presynaptic membrane of
      motoneurons, tetanus neurotoxin (TeNT) is internalized and transported
      retroaxonally to the spinal cord, where it blocks neurotransmitter release from
      spinal inhibitory interneurons. In contrast, the seven botulinum neurotoxins
      (BoNT) act at the periphery and inhibit acetylcholine release from peripheral
      cholinergic nerve terminals. TeNT and BoNT-B, -D, -F and -G cleave specifically
      at single but different peptide bonds, VAMP/synaptobrevin, a membrane protein of
      small synaptic vesicles. BoNT types -A, -C and -E cleave SNAP-25 at different
      sites within the COOH-terminus, whereas BoNT-C also cleaves syntaxin. BoNTs are
      increasingly used in medicine for the treatment of human diseases characterized
      by hyperfunction of cholinergic terminals.

PMID- 10936624
TI  - Iboga interactions with psychomotor stimulants: panacea in the paradox?
AB  - Currently, no effective therapy has been approved for the treatment of addiction
      to stimulant drugs (e.g., cocaine, amphetamine and its methylated derivatives).
      However, preclinical studies indicate that the naturally-occurring indole
      alkaloid, ibogaine, and a synthetic iboga alkaloid congener, 18
      methoxycoronaridine (18-MC), attenuate stimulant self-administration in
      laboratory animals. The in vivo pharmacological interactions between iboga agents
      and stimulant drugs are unclear. Ibogaine enhances the increase in accumbal
      dopamine produced by the acute administration of stimulant drugs. Consistent with
      these data, both ibogaine and 18-MC potentiate the expression of stimulant
      induced motor behaviors in acute and chronic stimulant-treated animals. To
      account for the paradox between their effects on self-administration and motor
      behavior, we proposed that iboga agents interfere with stimulant self
      administration by increasing sensitivity to their psychomotor-activating effects.
      However, this interpretation is contradicted by very recent observations that 18
      MC is without effect on the dopamine response to acute cocaine and that both
      ibogaine and 18-MC block the expression of sensitized levels of dopamine in the
      nucleus accumbens produced by chronic cocaine administration. Thus, a positive
      relationship exists between the effects of iboga pretreatment on stimulant
      induced dopamine sensitization and stimulant self-administration behavior. These
      data indicate that iboga agents might attenuate stimulant self-administration by
      reversing the neuroadaptations theoretically implicated in drug craving and
      compulsive drug-seeking behavior.

PMID- 10936625
TI  - Toxicity in animals. Trends in evolution?
AB  - Animals acquire toxicity either by metabolic synthesis of toxins (secondary
      metabolites), by expression of toxin genes or by the uptake, storage and
      sequestration of toxins produced by other organisms, i.e., microbes, plants or
      other animals. Variability of toxin structure and function is high. Peptide
      toxins in particular, although relying on a limited number of structural
      frameworks, often exhibit considerable structural hypervariability. An
      accelerated rate of evolution in the toxin gene structure (conserved introns, but
      high substitution rates in the exons) leads to the functional diversity of these
      peptides or proteins. The selective forces which may drive toxin evolution are
      unknown. Venomousness or the possession of toxins can be essential for survival,
      but the advantage of toxin biosynthesis may also be of minor importance or has
      been lost during evolution.

PMID- 10936626
TI  - The changing face of ciguatera.
AB  - Ciguatera is a global disease caused by the consumption of certain warm-water
      fish (ciguateric fish) that have accumulated orally effective levels of sodium
      channel activator toxins (ciguatoxins) through the marine food chain. Symptoms of
      ciguatera include a range of gastrointestinal, neurological and cardiovascular
      disturbances. This review examines progress in our understanding of ciguatera
      from the work of Banner in the late 1950s to the present. Similarities and
      differences in ciguatera in the Pacific Ocean, Indian Ocean and Caribbean Sea are
      highlighted, and future research directions are suggested.

PMID- 10936627
TI  - What does beta-bungarotoxin do at the neuromuscular junction?
AB  - beta-Bungarotoxin from the Taiwan banded krait, Bungarus multicinctus is a basic
      protein (pI=9.5), with a molecular weight of 21,800 consisting of two different
      polypeptide subunits. A phospholipase A(2) subunit named the A-chain and a non
      phospholipase A(2) subunit named the B-chain, which is homologous to Kunitz
      protease inhibitors. The A-chain and the B-chain are covalently linked by one
      disulphide bridge. On mouse hemi-diaphragm nerve-muscle preparations, partially
      paralysed by lowering the external Ca(2+) concentration, beta-bungarotoxin
      classically produces triphasic changes in the contraction responses to indirect
      nerve stimulation. The initial transient inhibition of twitches (phase 1) is
      followed by a prolonged facilitatory phase (phase 2) and finally a blocking phase
      (phase 3). These changes in twitch tension are mimicked, to some extent, by
      similar changes to end plate potential amplitude and miniature end plate
      potential frequency. The first and second phases are phospholipase-independent
      and are thought to be due to the B-chain (a dendrotoxin mimetic) binding to or
      near to voltage-dependent potassium channels. The last phase (phase 3) is
      phospholipase dependent and is probably due to phospholipase A(2)-mediated
      destruction of membrane phospholipids in motor nerve terminals.

PMID- 10936628
TI  - Over-the-counter psychotropics.

PMID- 10936629
TI  - Weight gain from novel antipsychotic drugs: need for action.
AB  - Obesity is common in schizophrenia, and people with schizophrenia appear to be at
      increased risk for certain obesity-related conditions, such as type 2 diabetes
      and cardiovascular disease. Antipsychotic drugs, used chronically to control
      symptoms of schizophrenia, are associated with often-substantial weight gain, a
      side effect that is a special concern with the latest generation of highly
      effective "novel" agents. That the most effective (e.g., novel) antipsychotic
      medications lead to substantial weight gain presents the field with a critical
      public health problem. Although preliminary data have been reported regarding the
      beneficial use of behavior therapy programs for short-term weight control in
      patients with schizophrenia, the available data are quite limited, and there are
      no data regarding the long-term beneficial effects of these programs in this
      population. The obesity field recently has developed programs emphasizing
      "lifestyle changes" (e.g., diet, exercise, and problem-solving skills) to
      successfully manage weight in patients without schizophrenia. Such programs can
      be adapted for patients with schizophrenia through the use of highly structured
      and operationalized modules emphasizing medication compliance, social skills
      development, and participation in outpatient programs. Moreover, these programs
      can potentially be combined with the use of adjunctive pharmacotherapy to
      maximize and maintain weight loss. The field must solve the paradox that some of
      our most effective medications for schizophrenia produce substantial weight gain
      and its associated troubling health risks.

PMID- 10936630
TI  - Who uses over-the-counter psychotropics? Characteristics, functioning, and
      (mental) health profile.
AB  - As part of a population study on the prevalence of psychopathology, users of
      "Over-The-Counter" Psychotropics (OTC-Ps) were studied. First, their mental
      health profile was examined by a number of subjective and objective assessments.
      Second, the medical consumption of the users was studied with special attention
      to the psychotropic drugs prescribed. The prevalence of psychological problems
      and symptoms of psychological distress was higher among OTC-P users than among
      non-users. Somatic problems and symptoms were comparable in the two groups;
      social support was better in the OTC-P users. Half of the users were known to
      have mental health problems by their Primary Care Physician (PCP). The DSM IV
      Axis I disorders were mostly mood and anxiety disorders. A benzodiazepine had
      been prescribed to one-third of the OTC-P users. No other psychotropic drugs had
      been prescribed, and the medical consumption was comparable in the two groups.
      PCPs should be aware of concomitant OTC-Ps use.

PMID- 10936631
TI  - Factors associated with symptomatic improvement and recovery from major
      depression in primary care patients.
AB  - This article describes a post-hoc analysis of clinical and psychosocial factors
      and beliefs about health associated with treatment outcome in a sample of
      depressed primary care patients (N=181) randomly assigned to a standardized
      treatment or physician's usual care (UC). Different factors were found to predict
      clinical outcomes for treatment modality [UC vs. interpersonal psychotherapy
      (IPT) or nortriptyline (NT)] and the type of outcome evaluated (i.e., depressive
      symptoms at 8 months or symptomatic and functional recovery at 8 months). Factors
      associated with treatment-specific outcomes are also described. Consistent with
      prior studies, lower depressive symptom severity at 8 months was associated with
      higher baseline functioning, minimal medical co-morbidity, race, and standardized
      pharmacologic or psychotherapeutic treatment. Additionally, an interaction
      between treatment modality and health locus of control indicated that individuals
      perceiving more self-control of their health and who received a standardized
      treatment experienced greater depressive symptom reduction at 8 months. Factors
      associated with symptomatic and functional recovery from the depressive episode
      were also examined. Patients who received a standardized treatment (IPT or NT)
      perceived greater control of their health and lacked a lifetime generalized
      anxiety disorder or panic disorder were more likely to recover by month 8 than
      those who received usual care. While clinical severity and treatment adequacy
      play an important role in both symptomatic improvement and full recovery from a
      depressive episode, other key factors such as health beliefs and non-depressive
      psychopathology also influence recovery.

PMID- 10936632
TI  - Integrating mental health services into primary care for HIV-infected pregnant
      and non-pregnant women: Whole Life--a theoretically derived model for clinical
      care and outcomes assessment.
AB  - Poor women of color who are disproportionately both infected and affected by
      HIV/AIDS also face multiple lifestyle and psychosocial burdens that complicate
      effective delivery of health care, thereby contributing to their poorer
      prognosis. Addressing these factors within the context of HIV/AIDS primary care
      for women is the aim of Whole Life, a program to integrate mental health services
      into primary care for HIV-infected pregnant and non-pregnant women. Whole Life
      utilizes a theoretically derived clinical services model that provides data for
      both clinical care and patient outcomes research within the constraints of a
      clinical setting. During a woman's first two clinic visits, data are gathered in
      structured interviews with standardized instruments-adapted for relevance to the
      population-that meet clinical and service needs, as well as measure components of
      the Whole Life model. Interviews are conducted by existing front-line staff who
      have been trained in using these instruments to gather information typically
      recorded in clinical notes. The implementation of Whole Life to date clearly
      demonstrates the feasibility of mental health-primary care services integration
      in a publicly funded HIV primary care clinic serving poor women of color.

PMID- 10936633
TI  - Posttraumatic stress disorder in the primary care medical setting.
AB  - Posttraumatic stress disorder (PTSD) is a prevalent disorder that adversely
      affects 2-5% of the general population. Little is known about PTSD in the primary
      care setting. The purpose of the present study was to evaluate the utility of a
      screening instrument for PTSD (the PCL-C) in primary care and to examine
      comorbidity, disability, and patterns of healthcare utilization among persons
      with PTSD in this setting. Adult, English-speaking patients attending for routine
      medical care (N=368) participated in a two-stage screening consisting of the
      administration of a self-report measure for posttraumatic stress disorder (the
      PCL-C) followed by a structured diagnostic interview. Current (1-month)
      prevalence of PTSD was determined, as were current comorbid disorders. Brief
      functional impairment and disability indices were administered, and healthcare
      utilization in the prior 6 months was ascertained. 11.8% (standard error 1.7%) of
      primary care attendees met diagnostic criteria for either full or partial PTSD.
      Comorbidity with major depression (61% of cases of PTSD) and generalized anxiety
      disorder (39%) was common, but less so with social phobia (17%) and panic
      disorder (6%). Substance use disorder comorbidity (22%) was also fairly common.
      Patients with PTSD reported significantly more functional impairment than
      patients without mental disorders. Patients with PTSD also made greater use of
      healthcare resources than not mentally ill patients. PTSD frequently is
      encountered in primary care, and is associated with considerable functional
      impairment and healthcare utilization. Comorbidity with other mood and anxiety
      disorders is extensive. It remains to be seen if greater awareness and more
      aggressive treatment of PTSD in primary care will lead to improved functioning
      and reduced (or more appropriate) healthcare utilization. These are topics for
      further study.

PMID- 10936634
TI  - Psychiatric consultations and ethics consultations. similarities and differences.
AB  - Although consultation-liaison psychiatry and clinical ethics both developed
      largely in response to the problems engendered by the new medical technology and
      the dilution of the traditional doctor-patient relationship, they represent
      distinct fields that rely on different, but overlapping, domains of expertise. To
      be effective, ethics consultants often need to augment their own background with
      psychiatric knowledge and skills. Consultation-liaison psychiatrists are well
      prepared to contribute to clinical ethics but cannot serve effectively as ethics
      consultants without additional education and training. Several case examples are
      presented to elucidate these points and to illustrate the similarities and
      differences between psychiatric consultations and ethics consultations.

PMID- 10936635
TI  - Is akathisia associated with poor clinical response to antipsychotics during
      acute hospital treatment?
AB  - Previous studies have suggested that akathisia is associated with poor acute
      clinical response to antipsychotics and that low serum iron levels are associated
      with emergence of akathisia. To examine these relationships during routine
      clinical treatment, we studied patients with DSM-IV schizophrenia or
      schizoaffective disorder undergoing hospital treatment for acute psychotic
      exacerbations with doctor's choice medications. There were 34 subjects observed
      for at least 2 weeks. They were assessed at baseline and weekly by one rater with
      the Anchored Brief Psychiatric Rating Scale and by another rater with the Barnes
      Rating Scale for akathisia, with the two raters blind to each other's ratings.
      Serum ferritin and transferrin levels were obtained at baseline. Seventeen
      subjects developed akathisia. Subjects with and without akathisia did not differ
      in change in thinking disturbance or anxiety-depression scores over 2 weeks, or
      in serum ferritin or transferrin levels. We conclude that mild akathisia by
      itself is not strongly associated with initial response to low to moderate doses
      of antipsychotics in the acute clinical setting. Limitations of the study are
      discussed.

PMID- 10936636
TI  - The association of suicide attempts and comorbid depression and substance abuse
      in psychiatric consultation patients.
AB  - Substance abuse has been associated with attempted suicide and suicide. Few
      studies have examined the prevalence and associations of combined depression and
      substance abuse in suicide attempters. A chart review study of 1136 adult general
      hospital patients referred for psychiatric consultation between 1995 and 1998 was
      conducted to assess this further. Among 371 cases with self-harm, 311 (84%)
      attempted suicide. Suicide attempters were younger and diagnosed more often with
      comorbid substance abuse than patients without self-harm. Depressive disorders
      were found in 59% and substance abuse disorders in 46%. Comorbid depression and
      substance abuse was the most frequent category in suicide attempters, i.e., in
      37%. Self-reported suicide intent was associated with increasing age, male
      gender, and comorbid depression and substance abuse. The suicide rate in suicide
      attempters was 322 per 100,000 patient-years, and 131 per 100,000 in consultation
      patients without self-harm. It is concluded that comorbid depression and
      substance abuse is associated with attempted suicide in psychiatric consultation
      patients. Suicide attempters should be thoroughly assessed for substance abuse.
      The increased suicide rate in psychiatric consultation patients with and without
      suicide attempts warrants further research.

PMID- 10936637
TI  - Metabolic activity of cultured rat brainstem, hippocampal and spinal cord slices.
AB  - The use of cultured brain slices has become an accepted technique for the ex vivo
      analysis of neural mechanisms, yet the viability of this preparation is not
      routinely measured. The tetrazolium dye 3-(4, 5-dimethlythiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT) is reduced by active mitochondria to an
      insoluble purple precipitate which accumulates within living cells and is easily
      visualized with bright field or phase contrast microscopy. In this study, the MTT
      assay was used to assess the viability of cultured brainstem, hippocampal and
      spinal cord slices (150-300 micrometer) from 0 to 22 day-old neonatal rats at
      post-explant time points ranging from 2 to 29 days. After 2 weeks, 180-300
      micrometer cultured slices from 4-13 day old rats remained 90-100% viable. Those
      from 0-1 day old rats had similar viability but displayed peripheral tissue
      outgrowth. Slices from older 18-22 day rats were no longer viable after 10-14
      days. After 4 weeks, the thicker (300 micrometer) slices of hippocampus and
      spinal cord retained 75-89% viability, in contrast to the 50-74% viability of the
      brainstem. Thinner brainstem and hippocampal slices (150-220 micrometer) slices
      were less than 50% viable at 4 weeks. Morphologic characteristics of the brain
      regions gradually degenerated over the 4-week culture period. Slice viability was
      markedly influenced by tissue thickness, donor age and brain region. Use of the
      MTT assay provides an inexpensive and expeditious means to assess a significant
      functional parameter of regional slice viability under variable conditions and
      enhances the feasibility of this preparation for functional studies, such as
      those concerned with genetic and protein expression within circumscribed areas of
      the brain.

PMID- 10936638
TI  - In vivo spectrometric calcium flux recordings of intrinsic Caudate-Putamen cells
      and transplanted IMR-32 neuroblastoma cells using miniature fiber optrodes in
      anesthetized and awake rats and monkeys.
AB  - A method is described to enable the recording of transient intracellular calcium
      changes in deep brain structures in anesthetized and awake animals using a
      fluorescent indicator combined with in vivo optical detection methods. Optrodes
      were fabricated using a bifurcated fiber-optic cable with an attached infusion
      guide cannula. After intracranial implantation of an optrode, animals were
      prepared in the following manner, (1) rats (intra-striatal) and monkeys (intra
      putamen) were infused with the fluorescent calcium indicator, Oregon Green, to
      load intrinsic cells; or (2) rats were intra-striatally transplanted with a
      slurry of dye-loaded IMR-32 neuroblastoma cells via pipette ejection. Excitation
      light from an argon-ion laser was launched through the optrode and passed into
      the tissue. The resulting calcium-induced fluorescence signals were captured by
      the optrode, then detected and processed by externalized photomultiplier- and CCD
      based spectrometer electronics. In approximately 25% of all intrinsic cell
      recordings, the baseline fluorescence intensity was relatively stable over time
      whereas in the remainder, large amplitude oscillations were observed with a
      frequency in the range of 0.5-2 Hz. These Ca(2+) transients were inhibited by
      local infusion of 10 microM omega-conotoxin MVIIC and 1 microM TTX. Extracellular
      electrophysiological recordings that were made adjacent to the optrode tip
      revealed that the Ca(2+) oscillations were in phase with the burst firing of
      striatal neurons. This suggested that the optical signals had a neuronal origin,
      most likely from medium spiny neurons. Baseline fluorescence intensity increased
      during infusion of high [K(+)](o), the calcium ionophore, A-23187, or during
      temporary bilateral carotid artery occlusion. Monkey (Saimiri sciureus) putamen
      recordings also affirmed the presence of similar calcium-related transients in a
      non-human primate. In the transplant preparations, the IMR-32 cells displayed a
      stable, non-oscillating baseline fluorescence. They were similarly responsive to
      high [K(+)](o) challenge and appeared viable for at least several hours. Similar
      optical recording approaches might be applied to monitor other fluorescent,
      chemiluminescent or bioluminescent events from almost any brain structure.
      Moreover, transplanted transfected cells expressing a single specific receptor or
      ion-channel protein may effectively serve as biosensing elements for the
      measurement of extracellular neurochemical signaling.

PMID- 10936639
TI  - Two-compartment model for whole-cell data analysis and transient compensation.
AB  - Recording and analysis of neuronal patch-clamp data involve many assumptions
      about membrane properties and cell morphology. Some of these assumptions
      introduce large errors or oversimplifications into the results. In particular,
      dendritic branching with high intracellular resistance leads to difficulty with
      capacitance calculation and transient subtraction, and may significantly distort
      measured currents. A two-compartment model, presented in detail here, provides a
      simple method of reducing many of these problems for the relatively simple case
      of cultured neurons studied with whole-cell patch electrodes. Some passive
      membrane properties may be accurately calculated, and the results may be used to
      correct recorded currents for resulting series resistance, intracellular
      resistance, and capacitive transient errors. The model may be tailored to
      particular cell types or experimental conditions. Programs to implement the
      algorithms are available from http://www.its.caltech.edu/ approximately
      nadeau/Rscomp.html.

PMID- 10936640
TI  - Quantitation of tyrosine hydroxylase protein in the locus coeruleus from
      postmortem human brain.
AB  - In this study, we developed an immuno-autoradiographic method to obtain
      quantitative estimates of tyrosine hydroxylase (TH) protein in tissue sections
      from post-mortem human brain. Protein from tissue sections containing the locus
      coeruleus (LC) was directly transferred to a polyvinylidene fluoride (PVDF)
      membrane. Immunoreactive TH on PVDF membranes was identified with optimized
      concentrations of TH antibody followed by application of [125I]labeled secondary
      antibody. Quantities of TH on autoradiograms were estimated by comparing optical
      densities of transferred immunoblots to a calibrated standard curve produced with
      purified recombinant TH dotted onto the same PVDF membranes. Amounts of TH
      immunoreactivity in the LC were proportional to the thickness of tissue sections
      up to 15 micrometer. However, the amounts of total protein, as measured by
      Ponceau S staining, were linearly related to section thicknesses up to 30
      micrometer. Comparisons of quantities of immunoreactive TH in the LC using this
      method to amounts determined using traditional Western blotting, in which LC
      tissue was punched from adjacent sections from the same subject, showed a
      positive correlation (r(2)=0.99, P<0.01). Using the transfer immunoblot method,
      an uneven distribution of TH protein was observed along the rostrocaudal axis of
      the human LC (P<0.01). This method may provide a sensitive and useful tool for
      the study of the role of human TH expression in the pathophysiology of
      psychiatric disease.

PMID- 10936641
TI  - Quantification of relative mRNA expression in the rat brain using simple RT-PCR
      and ethidium bromide staining.
AB  - We developed a protocol for quantification of relative gene expression using
      reverse transcription-polymerase chain reaction (RT-PCR) without the use of
      radioisotopes, special equipment or extra nucleotide fragments, such as
      competitors. The relative gene expression of GABA(A) receptor beta(1) subunit
      (GABA(A)Rbeta(1)) and phospholipase C beta(4) subtype (PLCbeta(4)) in rat
      cerebrum and cerebellum were determined by comparing the ratio of PCR products
      generated by linear amplification of the target cDNA segments and glyceraldehyde
      3-phosphate dehydrogenase (GAPDH) cDNA segment as a reference. The density of PCR
      products was measured from digitized images of photographs of ethidium-bromide
      stained agarose gels. The linear region of PCR amplification was within the
      linear range (from 0.3 to 12 ng DNA in a single band) of the detection system.
      The accuracy of the present method was <2-fold difference in gene expression in a
      single determination and a 1.5-fold difference was statistically significant
      after repeated measurements. The estimated relative expression of PLCbeta(4) was
      significantly higher in cerebellum than cerebrum, and that of GABA(A)Rbeta(1) was
      the same in these two regions. Using the present method, it is possible to
      quantify several different subunits and subtypes of known ion channel,
      neurotransmitter receptor and intracellular signaling enzyme gene families.

PMID- 10936642
TI  - Methods for detection of haematogenous dissemination of brain tissue after
      stunning of cattle with captive bolt guns.
AB  - Because of concern that the stunning of cattle with captive bolt guns (CBGs)
      could, if used on an animal with bovine spongiform encephalopathy (BSE), cause
      embolism of infective brain tissue and carcass contamination, the Ministry of
      Agriculture, Food and Fisheries commissioned research to assess the risk of
      haematogenous dissemination of CNS material after stunning. We have devised two
      methods to investigate this risk. The first involves the concentration of embolic
      tissue in buffy coat Cytoblocks that can be embedded for sectioning, microscopy
      and immunocytochemistry. The second method is an ELISA for the presynaptic
      protein, syntaxin 1B. The methods were validated by analysis of several bovine
      tissues, including blood samples deliberately contaminated with brain. We then
      studied jugular venous blood obtained before and after the stunning of 60 cattle
      with CBGs. Samples obtained, after stunning, from five of the cattle contained
      CNS tissue within the Cytoblocks and yielded positive syntaxin assays. Syntaxin
      was also detected in samples from one other animal that had been stunned with a
      pneumatically operated CBG. The described methods should allow an assessment of
      the risk of neuroembolism associated with different types of CBG and may also be
      useful in other contexts.

PMID- 10936643
TI  - A rapid and efficient method for the detection of point mutations of the human
      prion protein gene (PRNP) by direct sequencing.
AB  - Creutzfeldt-Jakob disease (CJD) and related disorders occur in sporadic, acquired
      and inherited forms. In sporadic, iatrogenic and new variant CJD the polymorphic
      codon 129 of the prion protein gene (PRNP) plays an important role for the
      susceptibility to the disease and for the clinical and neuropathological
      manifestations. All the inherited forms of CJD and related disorders are linked
      to point or insert mutations of PRNP. The analysis of PRNP is therefore important
      for a correct classification of these disorders and for the identification of
      novel mutations. The aim of the present study is to describe a fast and easy to
      perform method for the direct sequencing of the PCR amplified PRNP open reading
      frame, by using M13 tailed primers which allow a direct and rapid method of
      sequencing. The goodness of this method is demonstrated in the analysis of three
      sporadic CJD patients with different genotypes at codon 129 and three inherited
      cases bearing different point mutations of PRNP: the Pro102Leu mutation linked to
      Gerstmann-Straussler-Scheinker-syndrome, the Val210Ile mutation and a novel
      mutation at codon 211 (Gln211Glu) both associated to familial CJD.

PMID- 10936644
TI  - Simulation of cross-correlograms resulting from synaptic connections between
      neurons.
AB  - A cross-correlation simulation program is presented. It is intended for use as a
      rapid initial screening test, to discriminate between possible connection
      configurations that may underlie observed cross-correlations. It can also serve
      to introduce students to the event cross-correlation technique. The simulation
      employs a simple model of two neurons with noisy membranes that may excite or
      inhibit one another or receive a common input from a third neuron. The model
      differs from its predecessors in that the user specifies the neurons and their
      interconnections by the resulting membrane potential trajectories, rather than
      discharge statistics. Illustrations of some simple performance characteristics
      are given, as well as examples of cross-correlograms resulting from more complex
      interactions between neurons. The latter demonstrate the usefulness of the
      simulation in the interpretation of cross-correlograms obtained from experimental
      data. The simulation is a LabVIEW (National Instruments) program executable under
      the Windows operating system (Microsoft) and is available for downloading from
      website www.utoronto.ca/respgrp/sim.htm.

PMID- 10936645
TI  - A sealed cranial window system for simultaneous recording of blood flow, and
      electrical and optical signals in the rat barrel cortex.
AB  - We have developed a new sealed cranial window technique which allows the
      manipulation of simultaneously and independently multiple sensor probes, such as
      a glass microelectrode and a laser-Doppler probe. possible. Furthermore, normal
      intracranial pressure (4 mmHg) can be maintained throughout the craniectomy and
      the experiment. Using this technique, we have measured the neuronal activity and
      local cerebral blood flow together with the intrinsic optical properties in the
      rat barrel cortex during mechanical stimulation of the whiskers. The onset of the
      field response recorded by an extracellular electrode in the principal barrel
      columns occurred about 8 ms from the beginning of stimulation. These responses
      were well correlated with the whisker displacements (3 Hz, 2 s). The local
      cerebral blood flow, measured by laser-Doppler flowmetry, started to increase
      about 0.5 s after the first field response, peaked at about 1.7 s, and then
      gradually waned. A similar time-course of changes in the local blood volume was
      observed by simultaneous intrinsic optical imaging at the hemoglobin-isosbestic
      wavelength (570 nm). These results suggest that our technique would be useful for
      assessing the mechanism underlying neurovascular coupling under physiological
      conditions in vivo.

PMID- 10936646
TI  - A ventral approach to stereotaxy of the guinea pig brain.
AB  - The guinea pig (Cavia porcellus) is a species frequently used in
      neuromorphological and neurophysiological studies. Some experimental data suggest
      that the guinea pig might also be used to develop an animal model of Alzheimer's
      disease. These studies would require microsurgical manipulations of the nervous
      system. The present paper describes a method for ventral stereotaxic intrusions
      in the guinea pig brain through the oval foramen at the skull base. The
      topographic relationships of the bony landmarks to major parts of the central
      nervous system and the cranial nerves are analysed, and the results are tested by
      intrahippocampal injection of horseradish peroxidase.

PMID- 10936647
TI  - Novel method of monitoring electroencephalography at the site of microdialysis
      during chemically evoked seizures in a freely moving animal.
AB  - This paper covers the design, development and operation of a novel piece of
      equipment, based around the CMA/12 guide probe (Carnegie Medicin, Sweden), which
      offers a low cost alternative for monitoring EEG at the site of microdialysis in
      a freely moving animal. This equipment is entirely based on commercially
      available parts, and thus can be easily replicated. Moreover, it is less
      intrusive than earlier models, offering advantages for experiments in which
      behavioural testing or chronic monitoring is required. We illustrate its use in a
      study of changes in electrical seizure activity, in both cortex and basal nuclei,
      evoked by the administration of the chemoconvulsant soman. The inference from the
      many experimental paradigms looking at the mechanisms of chemoconvulsants is that
      paroxysmal discharges are a better correlate of seizure activity than behavioural
      signs. The correlation of the EEG with extracellular neurotransmitter data, over
      a period of hours post-injection of chemoconvulsant, allows the determination of
      whether extracellular neurotransmitter changes are a cause or consequence of the
      evoked electrical activity.

PMID- 10936648
TI  - Pharmacology of recombinant human GABA(A) receptor subtypes measured using a
      novel pH-based high-throughput functional efficacy assay.
AB  - To facilitate the discovery of novel compounds that modulate human GABA(A)
      receptor function, we have developed a high throughput functional assay using a
      fluorescence imaging system. L(tk-) cells expressing combinations of human
      GABA(A) receptor subunits were incubated with the pH-sensitive dye 2',7'bis-(2
      carboxyethyl)-5-(and 6)-carboxyfluorescein, then washed and placed in a 96-well
      real-time fluorescence plate reader. In buffer adjusted to pH 6.9 there was a
      robust and persisting acidification response to addition of GABA, which was
      antagonised by the GABA(A) receptor antagonist bicuculline. The concentration
      response relationship for GABA was modulated by allosteric ligands, including
      benzodiazepine (BZ) site agonists and inverse agonists. The effects of BZ site
      ligands on the pH response to GABA for receptors containing alpha1beta3gamma2,
      alpha3beta3gamma2 or alpha5beta3gamma2 subunits were well correlated with results
      from electrophysiological studies on the same receptor subunit combinations
      expressed in Xenopus oocytes. Most modulatory compounds tested were found to be
      relatively unselective across the three subunit combinations tested; however,
      some showed subtype-dependent efficacy, such as diazepam, which had highest
      agonist effects on the alpha3beta3gamma2 subtype, substantial but lesser agonism
      on alpha1beta3gamma2 and still substantial but the least agonism on
      alpha5beta3gamma2. This indicates that the alpha subunit within the recombinant
      receptor expressed in L(tk-) cells can affect the efficacy of the response to
      some BZ compounds. Inhibitors of Na(+)/Cl(-) cotransport, anion/anion exchange
      and the gastric type of H(+)/K(+) ATPase potently inhibited GABA-evoked
      acidification, indicating that multiple transporters are involved in the GABA
      evoked pH change. This novel fluorescence-based high throughput functional assay
      allows the rapid characterization of allosteric ligands acting on human GABA(A)
      receptors.

PMID- 10936649
TI  - A comparison of video and magnetic search coil recordings of mouse eye movements.
AB  - Interest in connecting molecular biology and behavior is motivating research into
      the eye movements of mice. Unfortunately, recording eye movements in this
      diminutive animal is technically difficult. We present the first method for
      obtaining calibrated video oculography, and contrast the results with
      simultaneously obtained scleral search coil recordings in C57BL/6 pigmented mice.
      We determined the distance of the pupil from the center of corneal curvature,
      based upon relative motions of the pupil and corneal reflections during camera
      movements, and used the distance to convert subsequent video measurements of
      pupil motion to eye rotation. We recorded responses during sinusoidal rotation
      (0.1-1.6 Hz) in the light, by video prior to search coil implantation, and by
      video and search coil simultaneously following implantation. Pre-implantation,
      video-derived gains ranged from 0.86+/-0.03 (mean+/-SD) at 0.1 Hz to 0.95+/-0.03
      at 0.8 Hz. Phase progressed monotonically from -3.1+/-2. 6 degrees (eye leads
      head) at 0.1 Hz to +5.9+/-1.1 degrees at 1.6 Hz. Coil implantation reduced the
      range of video-derived gains to 0. 64-0.79. This reduction reflects disruption of
      normal behavior by the coil. Coil data confirmed the video results. Video and
      search coil techniques each have advantages. Specific precautions are required
      when designing and interpreting experiments using the coil technique.

PMID- 10936650
TI  - Expansion of adult Schwann cells from mouse predegenerated peripheral nerves.
AB  - We present an effective technique for culture and expansion of Schwann cells (SC)
      from adult peripheral nerves. Cultures from adult mouse sciatic nerves (one to
      six nerves per culture) in defined medium showed markedly higher purity and
      density of SC when the nerve was predegenerated in vivo for 7 days than when it
      was harvested fresh. SC from degenerated nerves were then cultured in defined
      media conditioned by primary cultures of adult SC. The best results were obtained
      with a conditioned medium supplemented with 1% fetal calf serum. In these
      conditions the purity of SC was about 90% and the density about 190 cell/mm(2) by
      7-10 days in vitro. These findings indicate that adult SC can be expanded from
      small preinjured nerve fragments in a short time period to provide a source of SC
      for autologous cellular transplants.

PMID- 10936651
TI  - Neurotrophin 4/5 immunoassay: identification of sources of errors for the
      quantification of neurotrophins.
AB  - Neurotrophin 4/5 (NT4/5) is the least understood member of the mammalian
      neurotrophin family. Precise and reliable determinations of endogenous NT4/5
      levels are essential to understand its physiology. Immunoassay has been used for
      neurotrophin quantification for over three decades. However, this apparently
      simple task has proved elusive: conflicting results have long been recognized for
      nerve growth factor (NGF; up to 10000-fold variations in serum values have been
      reported in the literature) and more recently, for brain-derived neurotrophic
      factor (as much as 50-fold reported in rat hippocampus). Reasons for these
      variations have been extensively investigated by researchers, but rarely
      explained. During the development of our NT4/5 immunoassay, we discovered that
      false positive reactions resulted when tissues were extracted and assayed under
      certain conditions. In this study, we examined the major factors that adversely
      affect the quantification of NT4/5. Tissue samples from Sprague-Dawley rats were
      dissected and extracted in a range of buffers. The assay was performed on 96 well
      vinyl plates using sheep anti-NT4/5 immunoglobulin (Ig) as the capture (first)
      antibody, and a monoclonal anti-NT4/5 as the detector (second) antibody, followed
      by anti-mouse IgG (third) conjugated with peroxidase or alkaline phosphatase from
      several manufacturers. Our results show that: (1) tissue extraction at high or
      low pH, a method previously found to increase the measurable amount of NGF,
      produced greater false positive results for NT4/5 when compared with extraction
      at neutral pH; (2) the most significant source of error derived from the use of
      conjugated antibodies capable of reacting with molecules within tissue extracts
      which bind to the plate, even after thorough blocking; and (3) quantification is
      also significantly affected by both the standards used and the ability of the
      antibodies to react with these standards. Our findings indicate that the precise
      determination of neurotrophin levels requires quality reagents and the
      optimization of extraction conditions for each neurotrophin. The use of a two -
      rather than a three - antibody assay system avoids most of the interactions which
      give rise to false positive reactions.

PMID- 10936652
TI  - Low frequency voltage clamp: recording of voltage transients at constant average
      command voltage.
AB  - We implemented a simple feedback system that modifies the conventional current
      clamp mode of a patch clamp amplifier so that transient potentials, such as
      action potentials and synaptic potentials, can be measured as in the usual
      current clamp, while the average membrane potential is kept constant at a value
      chosen by the user. The circuit thus works like the current clamp for high
      frequency signals and like a voltage clamp for low frequency signals. We
      delineate its transfer properties and give application examples.

PMID- 10936653
TI  - Utility of the wavelet transform to analyze the stationarity of single ionic
      channel recordings.
AB  - Wavelet transform, a time-scale analysis, is presented as a new tool to analyze
      single-channel recordings. This method makes it possible to verify the
      stationarity, to identify episodes of change in the kinetic channel behavior
      (burst, flickering, cooperativity) or episodes of noise, and to localize
      stationary segments in long single-channel current recordings. It can help the
      conventional analysis of the kinetic behavior of ionic channels leading to better
      understand the gating mechanism.

PMID- 10936655
TI  - Kinetics of cutinase catalyzed transesterification in AOT reversed micelles:
      modeling of a batch stirred tank reactor.
AB  - A transesterification process is analyzed in its multiple kinetic components that
      include the determination of the kinetic constants for both substrates, butyl
      acetate (BAc) and hexanol (H), involved in the alcoholysis reaction and for the
      products formed (hexyl acetate (HAc) and butanol (B)), participating into the
      reverse reaction. The order of magnitude of these constants is discussed in
      relation with the AOT/isooctane reverse micellar system under study. The values
      of the equilibrium conversion (X(e)) and constant (K(eq)) were also determined.
      Diffusional limitations were detected for H concentrations lower than 450 mM and
      the correspondent effectiveness factors were calculated. Above 450 mM H the
      reaction is kinetically controlled. The operation of a batch stirred tank reactor
      (BSTR) was modeled considering the integrated rate equation for reversible
      kinetics.

PMID- 10936656
TI  - A fluorescence polarization assay using oligonucleotide probes for the rapid
      detection of verotoxin-producing Escherichia coli.
AB  - A hybridization assay using fluorescence polarization was combined with the
      asymmetric polymerase chain reaction (PCR) in a method for the detection of the
      verotoxin type 2 gene of verotoxin-producing Escherichia coli. Six
      oligonucleotide probes labeled with FITC were designed and evaluated. One of
      these gave a detection limit of 10(3) colony forming units per assay, and assay
      results could be obtained within 5 min after PCR. It appears that the detection
      limit was restricted mainly by the extent and fidelity of PCR amplification,
      rather than by the sensitivity of the fluorescence polarization technique,
      indicating that good probe design facilitates the rapid detection of the PCR
      product. The fluorescence polarization assay, in conjunction with DNA
      amplification by PCR, is a powerful and widely applicable method for the rapid
      and sensitive detection of oligonucleotide sequences.

PMID- 10936657
TI  - Effect of nitrogen source and nitrogen concentration on the production of
      pyruvate by Torulopsis glabrata.
AB  - The effect of nitrogen sources including yeast extract, peptone, soybean
      hydrolyzate and some inorganic nitrogen sources, as well as the nitrogen
      concentration on the fermentative production of pyruvate by Torulopsis glabrata
      WSH-IP12 was investigated. The addition of yeast extract greatly inhibited
      pyruvate accumulation, while peptone was shown to be the most favorable nitrogen
      source. In flask culture, 15 g l(-1) peptone was needed to consume 80 g l(-1)
      glucose with 23.4 g l(-1)of pyruvate accumulated. Pyruvate production was
      markedly dependent on the ratio of carbon to nitrogen (C:N), its production was
      improved by increasing the concentration of glucose and peptone proportionally
      and reduced by exclusively increasing the glucose concentration. In a glucose fed
      batch culture, cell growth and pyruvate production slowed after 28 h. However,
      cell growth and pyruvate production recovered after further nitrogen, in the form
      of peptone and ammonium sulfate, was added to the culture. A final concentration
      of pyruvate of 54.5 g l(-1) was achieved at 64 h (yield to glucose consumed of
      0.471 g g(-l)). By using aqueous ammonia instead of potassium hydroxide for pH
      control, 57.3 g l(-1) pyruvate with a yield of 0.498 g g(-1) was produced by 55
      h. This result further indicates that nitrogen level plays an important role in
      the production of pyruvate.

PMID- 10936658
TI  - Expression of glucose oxidase by using recombinant yeast.
AB  - The glucose oxidase gene (GO) of Aspergillus niger was cloned into the yeast
      shuttle vector YEp352 with combinations of various promoters and terminators, and
      then used to transform Saccharomyces cerevisiae. Expressed GO was successfully
      secreted into culture medium due to the presence of the intrinsic signal peptide
      of GO. Four different promoters fused to GO were tested: bidirectional galactose
      dehydrogenase 1 and 10 (GAL1, GAL10) promoters, glyceraldehyde-3-phosphate
      dehydrogenase (GPD) promoter and an yeast hybrid ADH2-GPD promoter consisting of
      alcohol dehydrogenase II (ADH2) and GPD promoter. The intrinsic terminator of GO
      as well as the GAL7 terminator were also compared for better production of GO.
      Deletion of most of the terminating region from GO yielded only a slight amount
      of GO while the presence of either terminator greatly increased GO production.
      The GAL10 promoter produced the least amount of GO, GAL1 and GPD promoters were
      moderate, and the ADH2-GPD hybrid promoter was the best among all tested.
      However, the hybrid promoter was tightly regulated by the presence of an excess
      amount of either glucose or ethanol, and it appeared that 2% glucose and 1. 5%
      ethanol supplement was the best concentration for GO production. It was possible
      to produce 260 IU ml(-1) of GO, an equivalent of 5 g l(-1), under the presence of
      2% glucose and 1.5% ethanol. UV mutagenesis of a recombinant S. cerevisiae was
      also applied and it further increased the yield of GO to 460 IU ml(-1) under the
      presence of 2% glucose and 1.5% ethanol without any changes in cell growth. Corn
      steep liquor which is commonly used in bioindustry is a good alternative
      substrate for high priced glucose for the hybrid promoter and suggests a cost
      effective means for commercial mass production of GO using recombinant yeast.

PMID- 10936659
TI  - Increased ability of transgenic plants expressing the bacterial enzyme ACC
      deaminase to accumulate Cd, Co, Cu, Ni, Pb, and Zn.
AB  - Transgenic tomato plants Lycopersicon esculentum (Solanaceae) cv. Heinz 902
      expressing the bacterial gene 1-aminocyclopropane-1-carboxylic acid (ACC)
      deaminase, under the transcriptional control of either two tandem 35S cauliflower
      mosaic virus promoters (constitutive expression), the rolD promoter from
      Agrobacterium rhizogenes (root specific expression) or the pathogenesis related
      PRB-1b promoter from tobacco, were compared to non-transgenic tomato plants in
      their ability to grow in the presence of Cd, Co, Cu, Mg, Ni, Pb, or Zn and to
      accumulate these metals. Parameters that were examined include metal
      concentration and ACC deaminase activity in both plant shoots and roots; root and
      shoot development; and leaf chlorophyll content. In general, transgenic tomato
      plants expressing ACC deaminase, especially those controlled by the PRB-1b
      promoter, acquired a greater amount of metal within the plant tissues, and were
      less subject to the deleterious effects of the metals on plant growth than were
      non-transgenic plants.

PMID- 10936660
TI  - Expression of a mammalian alpha 2,6-sialyltransferase gene in Pichia pastoris.
AB  - Terminal sialic acid on oligosaccharides of glycoproteins shows several
      biological functions of the glycoproteins. The yeast Pichia pastoris normally
      does not contain sialic acid on the oligosaccharides of glycoproteins. A
      sialyltransferase (ST) gene was transfected into P. pastoris to assess the
      possibility of using yeast cells as a host to produce sialoglycoproteins. The
      expression vectors pPIC3.5 and pPIC9 were used as carriers. The recombinant P.
      pastoris harbouring ST-pPIC3.5 and ST-pPIC9 had sialyltransferase activity of 1.1
      and 10.2 mU l(-1) respectively. The ability of the recombinant ST-pPIC3.5 and ST
      pPIC9 to transfer the fluoresceinyl-NeuAc into the cell glycoproteins was 36.9
      and 20.9 pmol mg -1 protein respectively.

PMID- 10936661
TI  - Molecular cloning of a gene encoding the thermoactive levansucrase from Rrahnella
      aquatilis and its growth phase-dependent expression in Eescherichia coli.
AB  - A levansucrase gene (lsrA) from Rahnella aquatilis ATCC33071 was isolated from a
      genomic library and the nucleotide sequence of the lsrA structural gene was
      determined. lsrA is composed of 1248 bp and encodes 415 amino acid residues with
      a calculated molecular mass of 45.9 kDa. Although the amino acid sequence of lsrA
      gene showed good conservation with the sequences of reported levansucrases and of
      the conserved regions thought to be implicated in the enzyme activity, comparison
      of the deduced amino acid sequences certified the dissimilarity of the proteins
      from Gram-negative and Gram-positive bacteria. The lsrA gene was expressed from
      its own promoter in Escherichia coli in an active form. The lsrA expression in E.
      coli-pRL1CPR was affected by the growth phase of cells: it was repressed in the
      early phase of growth, but was significantly stimulated during the entrance of
      cells into the late phase of growth. The growth-phase-dependent fashion of lsrA
      expression was altered in a constitutive-like fashion by the deletion of an
      upstream region of lsrA (pNd137), suggesting that the growth-phase dependent
      expression of lsrA was mediated by the deleted upstream region.

PMID- 10936663
TI  - Polygalacturonase is the key component in enzymatic retting of flax.
AB  - Seven commercial enzyme mixtures were tested for their ability to perform retting
      of flax (i.e. to separate flax fibers by partly removal of middle lamella) and
      were assayed for hydrolysis of xylan, cellulose and four kinds of pectin. The
      only activity that showed correlation to the ability to perform retting was the
      degradation of low esterfied pectin. A purified Aspergillus niger
      polygalacturonase was also shown to be able to perform retting. From this data it
      is hypothesized that degradation of the smooth regions (i.e. non-methylated
      polygalacturonase) in the middle lamella pectin is the most important step in
      enzymatic retting.

PMID- 10936662
TI  - Purification and partial characterization of fructosyltransferase and invertase
      from Aspergillus niger AS0023.
AB  - Fructosyltransferase (EC.2.4.1.9) and invertase (EC.3.2.1.26) have been purified
      from the crude extract of Aspergillus niger AS0023 by successive chromatographies
      on DEAE-sephadex A-25, sepharose 6B, sephacryl S-200, and concanavalin A
      Sepharose 4B columns. On acrylamide electrophoresis the two enzymes, in native
      and denatured forms, gave diffused glycoprotein bands with different
      electrophoretic mobility. On native-PAGE and SDS-PAGE, both enzymes migrated as
      polydisperse aggregates yielding broad and diffused bands. This result is typical
      of heterogeneous glycoproteins and the two enzymes have proved their glycoprotein
      nature by their adsorption on concanavalin A lectin. Fructosyltransferase (FTS)
      on native PAGE migrated as two enzymatically active bands with different
      electrophoretic mobility, one around 600 kDa and the other from 193 to 425 kDa.
      On SDS-PAGE, these two fractions yielded one band corresponding to a molecular
      weight range from 81 to 168 kDa. FTS seems to undergo association-dissociation of
      its glycoprotein subunits to form oligomers with different degrees of
      polymerization. Invertase (INV) showed higher mobility corresponding to a
      molecular range from 82 to 251 kDa, on native PAGE, and from 71 to 111 kDa on SDS
      PAGE. The two enzymes exhibited distinctly different pH and temperature profiles.
      The optimum pH and temperature for FTS were found to be 5.8 and 50 degrees C,
      respectively, while INV showed optimum activity at pH 4.4 and 55 degrees C. Metal
      ions and other inhibitors had different effects on the two enzyme activities. FTS
      was completely abolished with 1 mM Hg(2+) and Ag(2+), while INV maintained 72 and
      66% of its original activity, respectively. Furthermore, the two enzymes
      exhibited distinctly different kinetic constants confirming their different
      nature. The K(m) and V(m) values for each enzyme were calculated to be 44.38 mM
      and 1030 micromol ml(-1)min(-1) for FTS and 35.67 mM and 398 micromol ml(-1) min(
      1) for INV, respectively. FTS and INV catalytic activity was dependent on sucrose
      concentration. FTS activity increased with increasing sucrose concentrations,
      while INV activity decreased markedly with increasing sucrose concentration.
      Furthermore, INV exhibited only hydrolytic activity producing exclusively
      fructose and glucose from sucrose, while FTS catalyzed exclusively
      fructosyltransfer reaction producing glucose, 1-kestose, nystose and
      fructofuranosyl nystose. In addition, at 50% sucrose concentration FTS produced
      fructooligosaccharides at the yield of 62% against 54% with the crude extract.

PMID- 10936664
TI  - The role of platelets in diabetes-related vascular complications.
AB  - The contribution of platelets to the pathogenesis and progression of vascular
      complications in diabetes is supported by several studies. In general, platelets
      obtained from diabetic subjects show increased adhesiveness and an exaggerated
      aggregation, both spontaneous and in response to stimulating agents. The causes
      for this activation are multifold: altered exposure and/or abundance of
      glycoprotein receptors for agonists and adhesive proteins on the platelet
      surface, increased binding of fibrinogen, decreased membrane fluidity, altered
      platelet metabolism and changes in intraplatelet signalling pathways. The altered
      biophysical state of platelet membrane components in diabetes mellitus may be one
      of the major determinants of platelet hypersensitivity and hyperfunction and may
      contribute to impairments in various metabolic pathways, like intensified calcium
      mobilisation and accentuated thromboxane synthesis and release. Activated
      platelets interact with other cells, such as endothelial cells and leukocytes as
      well with the coagulation system in the process of atherosclerosis. Some studies
      indicated that platelet dysfunction was especially apparent in diabetic subjects
      with macro- or microangiopathy, while others showed that it may be related to the
      presence of diabetes mellitus per se. Several pharmaceutical compounds have been
      developed for the inhibition of platelet activation. However, aspirin treatment
      is cheap and effective, and aspirin remains to be the drug of choice for diabetic
      patients. It should be prescribed widely for patients who are at high risk of
      cardiovascular events.

PMID- 10936665
TI  - Identity of mouse IA-2 and PTP35 genes of the tyrosine phosphatase family, and
      their expression in neuroendocrine tissues.
AB  - Recently, IA-2, one of the major diabetic autoantigens, and PTP35 cDNA were
      independently isolated by subtraction cloning using insulinoma cells and a
      polymerase chain reaction (PCR)-based search for conserved sequences using NIH3T3
      fibroblast cell line, respectively. By Southern blot analysis and nucleotide
      sequence determination of reverse transcription PCR products, we showed that IA-2
      and PTP35 are identical and exist as a single gene in a mouse genome. The
      expression of IA-2/PTP35 messages was detected by northern blot analysis in
      MIN6N8 cells, an insulinoma cell line derived from non-obese diabetic mice, but
      its expression level was not affected by the ambient glucose level, phorbol-12
      myristate 13-acetate or tumour necrosis factor-alpha. We also generated
      polyclonal antibodies to murine IA-2/PTP35 by immunization with recombinant
      proteins. Subsequent immunohistochemical analysis using these polyclonal
      antibodies disclosed that IA-2/PTP35 is strongly expressed in mouse
      neuroendocrine tissues such as pancreatic islets and the hypothalamus-pituitary
      gland. These results suggest that IA-2/PTP35 functions primarily in
      neuroendocrine tissues.

PMID- 10936666
TI  - Type 2 diabetes and oral health: a comparison between diabetic and non-diabetic
      subjects.
AB  - A controlled cross-sectional study with the aim of studying oral health in
      patients with type 2 diabetes was carried out in a health care district in
      Sweden. The study included 102 randomly sampled diabetic patients and 102 age-
      and gender-matched non-diabetic subjects from the same geographical area, treated
      at the same Public Dental Service clinics. Oral conditions were measured at
      clinical and X-ray examinations. Diabetes-related variables were extracted from
      medical records. Diabetic patients suffered from xerostomia (dry mouth) to a
      significantly higher degree than non-diabetic controls did (53.5 vs. 28.4%;
      P=0.0003). Sites with advanced periodontitis were more frequent in the diabetic
      group (P=0.006) as were initial caries lesions (P=0.02). Diabetic subjects showed
      a greater need of periodontal treatment (P=0.05), caries prevention (P=0.002) and
      prosthetic corrections (P=0.004). Diabetes duration or metabolic control of the
      disease was not related to periodontal status. However, patients with longer
      duration of diabetes had more manifest caries lesions (P=0.05) as had those on
      insulin treatment when compared with patients on oral/diet or combined treatment
      (P=0.0001). The conclusion is that individuals with type 2 diabetes in some oral
      conditions exhibited poorer health. Close collaboration between the patient, the
      primary health care and oral health professionals could be a way of improving the
      diabetic patient's general and oral health.

PMID- 10936667
TI  - Excess costs of medical care 1 and 8 years after diagnosis of diabetes: estimates
      from young and middle-aged incidence cohorts in Sweden.
AB  - To analyze the excess costs of medical care during the first decade after
      diabetes diagnosis, we surveyed two national incidence cohorts who contracted
      diabetes at age of 15-34 years and matched control groups from the general
      population of Sweden. Ninety percent of the diabetic subjects were on insulin
      treatment. Data on healthcare utilization and use of glucose lowering drugs and
      medical devices were collected via a questionnaire mailed to a recent cohort 1
      year after diagnosis and a previously registered cohort 8 years after diagnosis.
      Costing was based on average national costs of hospital inpatient and out-patient
      care, an original study of daycare costs, and sales prices of the National
      Corporation of Swedish Pharmacies. One year after diabetes diagnosis, the annual
      excess costs of care were US$4743 among men and US$4976 among women (1997
      prices). Hospital inpatient care accounted for more than 50% of the excess costs.
      Eight years after diagnosis, the excess costs were US$2010 among men and US$2734
      among women. The higher costs for women were mainly related to hospital out
      patient care, but also to more intensive self-monitoring. We conclude that
      diabetes in young and middle-aged people is a major economic challenge even
      before significant complications may have developed.

PMID- 10936669
TI  - Comparison of the validity of the criteria for gestational diabetes mellitus by
      WHO and by the Japan Society of Obstetrics and Gynecology by the outcomes of
      pregnancy.
AB  - Data for 416 Japanese pregnant women who received a 75g oral glucose tolerance
      test (OGTT) for determination of gestational diabetes mellitus (GDM) in 13
      hospitals in Japan were analyzed retrospectively. Comparison of the diagnostic
      criteria of the World Health Organization (WHO) and the Japan Society of
      Obstetrics and Gynecology (JSOG) revealed pregnant women who met the latter
      criteria for GDM to have significantly higher incidences of low Apgar scores,
      respiratory problems, neonatal hypoglycemia, preterm delivery and requirements
      for insulin therapy and cesarean section. The women who met the WHO criteria but
      not the JSOG criteria had minor complications. These observations suggest that
      the GDM criteria of the JSOG are more appropriate than the WHO criteria from the
      standpoint of therapeutic intervention for pregnant women.

PMID- 10936668
TI  - Efficacy and safety of acarbose add-on therapy in the treatment of overweight
      patients with Type 2 diabetes inadequately controlled with metformin: a double
      blind, placebo-controlled study.
AB  - This 6-month, double-blind, placebo-controlled, randomised, parallel-group study
      investigated the potential of acarbose add-on therapy for improving the glycaemic
      control of overweight patients with Type 2 diabetes and was inadequately
      controlled with metformin monotherapy. Patients were randomised to receive
      acarbose titrated up to 100 mg three times daily (n=74) or placebo (n=78). All
      patients were receiving metformin 850 mg twice or thrice daily before the study
      and continued to receive this dose throughout the study. The mean difference in
      glycated haemoglobin (HbA(1c)) (+/-S.D.) from baseline to endpoint was -0.7+/
      1.2% U in the acarbose intention-to-treat (ITT) group, compared with +0.2+/-1.3%
      in the placebo ITT group (P=0.0001). Significantly, more patients in the acarbose
      group were classified as 'responders', with an HbA(1c) at the end of treatment of
      less than 7.0% or a decrease by at least 15% relative to baseline (acarbose vs.
      placebo; 42 vs. 17%; P=0.002). The difference in fasting blood glucose level from
      baseline to endpoint was -1.0+/-2.8 (S.D.) mmol/l in the acarbose ITT group,
      compared with +1.3+/-2.8 mmol/l in the placebo ITT group (P=0.0001), and for 2-h
      postprandial blood glucose level -1.4+/-3.8 vs. +1.1+/-3.5 mmol/l (P=0.0001). In
      all, 60% of patients in the acarbose group and 33% in the placebo group had an
      adverse event considered to be possibly or probably related to drug therapy,
      leading to withdrawal by 15 and 3%, respectively. The results indicate that
      acarbose has potential clinical utility for improving glycaemic control in
      overweight patients with Type 2 diabetes inadequately controlled with metformin.

PMID- 10936670
TI  - Relation of serum total sialic acid concentrations with diabetic complications
      and cardiovascular risk factors in Kuwaiti Type 2 diabetic patients.
AB  - Serum total sialic acid is a marker of the acute phase response. Elevated levels
      have also been associated with cardiovascular disease in the general Caucasian
      population and especially in Type 2 diabetic subjects. The purpose of this study
      was to estimate serum total sialic acid concentrations among Kuwaiti Type 2
      diabetic subjects and to investigate its association with macro and microvascular
      diabetes-related complications in that population. Serum total sialic acid levels
      were estimated by an enzymatic spectro-photometric assay in two groups of
      subjects: (i) 358 Kuwaiti Type 2 diabetics (156 men and 202 women) referred for
      their annual evaluation to the specialised diabetic clinic at the main university
      teaching hospital in Kuwait, and (ii) 47 healthy age and sex matched non-diabetic
      Kuwaiti control population (13 men and 34 women). Serum sialic acid levels were
      significantly higher (P<0.001) among the diabetic patients (mean+/-S.D.) (81.2+/
      13.2 mg/dl) compared to the non-diabetic controls (66.9+/-11.0 mg/dl). Kuwaiti
      diabetic women had significantly higher concentrations compared to diabetic men
      (85.2+/-12.1 vs. 75.9+/-13.0 mg/dl, P<0.001). Among the controls there was no
      significant gender difference in sialic acid levels of women, (68.3+/-11.6 mg/dl)
      versus men (63.2+/-8.2 mg/dl). The gender difference in the diabetic patients was
      unrelated to the degree of obesity. Significant correlations were found between
      serum total sialic acid concentrations and such cardiovascular risk factors as
      plasma levels of apolipoprotein B, low density lipoprotein cholesterol,
      triglycerides and uric acid in the diabetic subjects. Furthermore, there was a
      significant elevation in serum total sialic acid concentrations with increasing
      urinary albumin excretion, P<0.001, but not with retinopathy or neuropathy.

PMID- 10936671
TI  - Membrane type 1-matrix metalloproteinase expression is regulated by E-cadherin
      through the suppression of mitogen-activated protein kinase cascade.
AB  - To elucidate the role of E-cadherin in matrix metalloproteinases (MMPs)
      expression, we transfected to squamous carcinoma cells with E-cadherin cDNA. HN5
      cells and mock-transfected HN5-neo cells expressed proMMP-2 and active MMP-2. E
      cadherin-transfected HN5-EC cells produced comparable proMMP-2 but low active MMP
      2; and membrane type 1-MMP (MT1-MMP) mRNA declined. Phosphorylated ERK, a marker
      of mitogen-activated protein (MAP) kinase cascade, also declined in HN5-EC cells.
      The addition of anti-E-cadherin antibody resulted in the disappearance of these
      alterations in HN5-EC cells. These results suggest that E-cadherin suppresses MAP
      kinase cascade and down-regulates MT1-MMP.

PMID- 10936672
TI  - Cellular uptake, subcellular localization and photodamaging effect of temoporfin
      (mTHPC) in nasopharyngeal carcinoma cells: comparison with hematoporphyrin
      derivative.
AB  - Temoporfin (meta-tetra (hydroxyphenyl)chlorin; mTHPC) potentiated a 100-fold
      higher cytotoxic effect than hematoporphyrin derivative (HPD) on two
      nasopharyngeal carcinoma cell lines (HK1 and CNE2) in terms of the overall
      photodynamic therapy (PDT) dose. The cellular uptake, evaluated by flow cytometry
      and spectrophotometry demonstrated that mTHPC exhibited higher uptake ability
      than HPD. Confocal laser scanning microscopy detection for both the sensitizer
      and mitochondria probe on the same cell images revealed that both drugs
      accumulated diffusely in the cytoplasm and that mitochrondria is a target
      organelle. Photo-activation ruptured the mitochrondria, with more pronounced
      mitochondrial damage being observed in mTHPC-PDT course. This correlated well
      with the cell photokilling efficiency of mTHPC.

PMID- 10936673
TI  - Tamoxifen enhances myoepithelial cell suppression of human breast carcinoma
      progression in vitro by two different effector mechanisms.
AB  - Our previous studies have indicated that myoepithelial cells surrounding ductal
      and acinar epithelium of glandular organs, such as the breast, exert multiple
      paracrine suppressive effects on incipient and developing cancers that arise from
      this epithelium. Myoepithelial cells and derived cell lines (HMS 1-6) exert these
      effects through the secretion of a number of different effector molecules that
      exert anti-invasive, anti-proliferative, and anti-angiogenic activities. Since
      previous basic and clinical studies have examined the role of estrogen agonists
      and antagonists on human breast cancer cells and because issues of hormone
      replacement therapy (HRT) and tamoxifen chemoprevention are such timely issues in
      breast cancer, we wondered whether or not hormonal manipulations might affect
      myoepithelial cells in vitro as far as their paracrine suppressive activities on
      breast cancer were concerned. The present in vitro study demonstrates that
      treatment of myoepithelial cells with tamoxifen but not 17beta-estradiol
      increases both maspin secretion and invasion-blocking ability. Furthermore
      tamoxifen but not 17beta-estradiol increases inducible nitric oxide synthase
      (iNOS) expression and nitric oxide (NO) production by myoepithelial cells when
      they are co-cultured with conditioned media from or breast carcinoma cells
      directly. This increased myoepithelial NO exerts both autocrine and paracrine
      antiproliferative effects which can be blocked by inhibition of iNOS. 17beta
      Estradiol, however, competes with all of these suppressive effects of tamoxifen
      suggesting that the mechanism of tamoxifen action is estrogen receptor mediated.
      Myoepithelial cells lack ER-alpha but express ER-beta. Tamoxifen, but not 17beta
      estradiol, increases AP-1 CAT but not ERE-CAT activity. Again, 17beta-estradiol
      competes with the transcription-activating effects of tamoxifen. These
      experiments collectively suggest that the actions of tamoxifen on the increased
      secretion of maspin and increased production of NO by myoepithelial cells are
      mediated through ER-beta and the transcription-activation of an ER-dependent AP-1
      response element.

PMID- 10936674
TI  - Farnesyl anthranilate suppresses the growth, in vitro and in vivo, of murine B16
      melanomas.
AB  - The numbers of isoprene residues and unsaturated bonds, cis/trans configuration,
      and head group polarity influence the tumor-suppressive potency of acyclic
      isoprenoid hydrocarbons and alcohols; within the series tested, trans, trans
      farnesol had the greatest potency. Geraniol esters had increased potency relative
      to that of the free alcohol. Farnesyl anthranilate induced a concentration
      dependent decrease in the B16 melanoma cell population, in part due to an
      increased proportion of cells in the G1 phase of the cell cycle and in part by
      the increased the proportion of apoptotic cells. Farnesyl anthranilate (1.5
      mmol/kg diet) significantly suppressed the growth of implanted B16 melanomas and
      lowered the plasma cholesterol levels of tumor-free mice.

PMID- 10936675
TI  - Infrequent loss of heterozygosity at adenomatous polyposis coli gene locus in
      Indian oral cancers.
AB  - We have investigated loss of heterozygosity (LOH) of the adenomatous polyposis
      coli (APC) tumor suppressor gene using polymerase chain reaction (PCR)
      restriction fragment length polymorphism (RFLP) in 86 untreated oral cancer
      patients, using matched oral cancer tissue and corresponding peripheral blood
      cell (PBC) DNA samples. PBC from 70 normal healthy individuals, were also
      analyzed for allelic distribution of APC gene. A 133 bp fragment, spanning exon
      11 of the APC gene was amplified, and RsaI digestion of the PCR product defined
      the alleles as either homozygous 133 bp (Rsa(-/-)) or 87 and 46 bp (Rsa(+/+))
      fragments, and heterozygous (Rsa(+/-)) exhibiting the three fragments.
      Distribution of the three alleles, Rsa(-/-), Rsa(+/+), and Rsa(+/-) in the oral
      cancer patients was observed as 10.5, 51.1 and 38.4%; whereas normal healthy
      individuals showed 11.4, 37.1 and 51.4%, respectively. In the informative
      heterozygous (Rsa(+/-)) oral cancer patients, LOH was infrequent, demonstrated in
      two of 33 (6%) samples. Thus, the APC gene was infrequently altered by LOH at the
      polymorphic RsaI locus in exon 11 in the tobacco associated Indian oral cancer,
      unlike the smoking tobacco/alcohol associated oral cancers from Western
      countries.

PMID- 10936676
TI  - Photothermic treatment of pigmented B16 melanoma using a broadband pulsed light
      delivery system.
AB  - Pulsed photothermic treatment (PTT) of pigmented B16 mice melanoma tumors was
      carried out using a Photodyne incoherent light delivery system. Tumor heating
      with average temperature of 41-44 degrees C was observed during broadband
      photoirradiation (600-800 nm) at light doses of 60-120 J/cm(2) delivered using
      0.6 J/cm(2) pulses (2 ms) at 1 Hz repetition rate. Electron microscopy of tumor
      samples revealed pronounced structural changes in microvasculature and
      melanosomes. Pulsed PTT caused damage to endothelial cells and vascular walls,
      swelling of mitochondria and melanosomal disruption without nuclear alteration.
      Significant tumor response with necrosis formation followed by tumor regression
      was observed by a tumor growth study after PTT at 120 J/cm(2).

PMID- 10936677
TI  - Methylation of a CpG island within the promoter region of the KAI1 metastasis
      suppressor gene is not responsible for down-regulation of KAI1 expression in
      invasive cancers or cancer cell lines.
AB  - The molecular basis for downregulation of the KAI1 metastasis suppressor gene in
      invasive and metastatic human cancers is unknown. We have used bisulphite
      methylation analysis of DNA from paraffin-embedded invasive bladder tumour
      samples and from bladder cancer cell lines to determine if hypermethylation of a
      CpG island within the KAI1 promoter is responsible for this effect.
      Representative invasive tumour cell lines were also exposed to 5-aza-2
      deoxycytidine. We found no evidence for hypermethylation of the CpG island and
      suggest that mechanisms other than promoter hypermethylation are responsible for
      reduced KAI1 expression in invasive bladder tumours and tumour cell lines.

PMID- 10936679
TI  - Beta-catenin and adenomatous polyposis coli (APC) mutations in adenomas from
      hereditary non-polyposis colorectal cancer patients.
AB  - To clarify the roles of the adenomatous polyposis coli (APC) and beta-catenin
      genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we
      searched for their mutations in 14 HNPCC adenomas with microsatellite instability
      (MSI). Seven (50%) adenomas exhibited somatic APC mutations, five of which were
      frameshift mutations and the other two nonsense ones. However, the APC mutational
      spectrum of these adenomas was similar to that of sporadic colorectal tumors. Two
      adenomas (14.3%) with undetectable APC alterations showed missense mutations at
      codon 45 (TCT to TTT or to CCT) in beta-catenin. The MSI frequency in adenomas
      with beta-catenin mutations was significantly higher than that with APCones
      (P<0.001), indicating that mutations of beta-catenin rather than APC are strongly
      associated with MSI. These data suggest that adenomas with beta-catenin
      activating mutations and some with APC inactivating mutations may be precursors
      of HNPCC colorectal cancers.

PMID- 10936678
TI  - Glioma cell extracellular matrix metalloproteinase inducer (EMMPRIN) (CD147)
      stimulates production of membrane-type matrix metalloproteinases and activated
      gelatinase A in co-cultures with brain-derived fibroblasts.
AB  - Extracellular matrix metalloproteinase inducer (EMMPRIN) also called CD147,
      basigin or M6 in the human is a member of the immunoglobulin superfamily that is
      enriched on the surface of tumor cells and stimulates adjacent stromal cells to
      produce several matrix metalloproteinases (MMPs). In this study, we have
      demonstrated that coculturing of EMMPRIN-expressing human glioblastoma multiforme
      cells (U251) with brain-derived human fibroblasts not only stimulates production,
      but also activation of pro-gelatinase A (proMMP-2), an enzyme that is enriched in
      malignant gliomas and most likely crucial to tumor progression. Production of
      membrane types 1 and 2-MMPs (MT1-MMP and MT2-MMP), which are activators of proMMP
      2, was also stimulated in these cocultures. Stimulation of MMP-2, MT1-MMP and MT2
      MMP production was inhibited by anti-EMMPRIN monoclonal antibody in a dose
      dependent manner. Thus, we have shown, for the first time, that EMMPRIN causes
      increased expression of MT1-MMP and MT2-MMP, as well as increased production and
      activation of MMP-2.

PMID- 10936680
TI  - A glutathione S-transferase inducer from papaya: rapid screening, identification
      and structure-activity relationship of isothiocyanates.
AB  - We have developed a simple system for rapid detection and measurement of
      glutathione S-transferase placental form (GSTP1) that detoxify polycyclic
      aromatic hydrocarbons using the cultured rat normal liver epithelial cell line,
      (RL34) cells. Survey of fruit extracts for GST inducing ability identified both
      papaya and avocado as significant sources. Benzyl isothiocyanate (BITC) was
      isolated from papaya methanol extract as a principal inducer of GST activity.
      Further, the GST inducing ability of a total of 20 isothiocyanates (ITCs) and
      their derivatives was investigated. Some ITCs showed significant induction, and
      BITC was one of the most potent inducers among all compounds tested in the
      present study. The modification of isothiocyanate group (-NCS) or introduction of
      substituent group to the alpha-carbon modifies GST induction. Moreover, a
      significant correlation (P<0.01, r=0.913) between the GST activity enrichment and
      GSTP1 protein induction by ITCs was observed. We also indicated that phenethyl
      ITC and nitrophenyl ITC, potently inducing GST activity, but not inactive benzyl
      isocyanate, are potential inducers of intracellular reactive oxygen intermediates
      (ROIs). Our system of GSTP1 induction is appropriate for the chemical research
      such as screening and identification of novel type of inducers as well as the
      structure-activity relationship studies, providing mechanistic insight into
      essential structural elements for GSTP1 induction.

PMID- 10936681
TI  - Role of E-cadherin in peritoneal dissemination of the pancreatic cancer cell
      line, panc-1, through regulation of cell to cell contact.
AB  - The present study was designed to clarify the molecules responsible for
      peritoneal dissemination of cancer cells. We established sublines with high (HP
      cells) and low (LP cells) passing activity through the membrane of a transwell
      chamber. The cell lines were established from the human pancreatic cancer cell
      line, Panc-1. LP cells demonstrated an octagonal shape and tight adhesion,
      whereas HP cells exhibited a spindle shape and grew with less cell-cell contact
      in vitro. It was found that HP cells demonstrated a high degree of peritoneal
      dissemination in nude mice following peritoneal injection of these cells compared
      to LP cells. We subsequently investigated the expression of certain adhesion
      molecules. Consequently, we found that LP cells exhibited a stronger expression
      of E-cadherin than HP cells. On the other hand, there was no difference in the
      expression of CD44H and beta1 integrin between these two sublines. Passing
      activity of LP cells through the membrane of the invasion chamber increased to
      nearly equal levels with HP cells following treatment with anti-human E-cadherin
      antibody. Moreover, transfection of mouse E-cadherin cDNA into HP cells reduced
      both passing activity through the membrane of the invasion chamber and peritoneal
      dissemination in nude mice to levels similar to that of LP cells. In conclusion,
      these results indicated that loss of E-cadherin facilitates both passing activity
      in an invasion chamber and peritoneal dissemination, playing a causative role in
      peritoneal dissemination of cancer cells.

PMID- 10936682
TI  - Failure to induce inhibition of cyclin A and up-regulation of p21 expression in
      phorbol ester-resistant U937 cells by phorbol ester.
AB  - Differentiation resistant U937 cells were derived from parental U937 cells by
      selecting for continuously growing U937 cells in cell cultures continuously
      exposed to phorbol 12 myristate 13-acetate (PMA). Unlike in other known PMA
      resistant U937, the basal expression of protein kinase C (PKC) isozymes in these
      PMA resistant cells (R-U937) was significantly decreased. Subsequent analyses
      revealed differences between the wild type U937 and the R-U937 cells with respect
      to G1 phase arrest, which seemed to occur in U937 because of low levels of cdk2
      kinase activity. This abolished cdk2 kinase activity is mainly due to inhibition
      of cdk2 phosphorylation, cyclin A down-regulation and cyclin dependent kinase
      inhibitor p21 up-regulation. Our data suggest that events down-stream of PKC
      activation may mediate cell cycle control. Thus, the R-U937 cells could be useful
      for further PKC mediated cell cycle control studies.

PMID- 10936683
TI  - Response of the rabbit diaphragm to tendon vibration.
AB  - To evaluate the potential role of diaphragmatic muscle spindles in the act of
      breathing, we have recorded the electromyograms of the diaphragm and the external
      intercostal muscle in the third interspace during high-frequency mechanical
      vibration (50 Hz) of the central tendon in eight anesthetized, spontaneously
      breathing rabbits. Vibration induced a consistent, clear-cut increase in the
      inspiratory activity recorded from the external intercostal, thus indicating that
      the mechanical stimulus applied to the diaphragm was strong enough to trigger
      muscle spindles at distant sites. However, vibration did not elicit any
      alteration in costal or crural diaphragmatic activity in any animal. Similarly,
      when vibration was applied during hyperventilation-induced apnea, activity was
      recorded in the external intercostal but not in the diaphragm. These observations
      support the traditional view that the diaphragm is poorly endowed with muscle
      spindles and that these play little or no significant role in the act of
      breathing.

PMID- 10936684
TI  - Changes in apoptosis-related protein (p53, Bax, Bcl-2 and Fos) expression with
      DNA fragmentation in the central nervous system in rats after closed head injury.
AB  - This study aimed to examine the temporal profile of neuronal apoptosis in the
      central nervous system (CNS) following closed head injury in rat. Fos
      immunoreactivity was detected in neuronal nuclei in the cerebral cortex at 2 h
      after head injury. At 4 h, Bax protein expression was elevated with a concomitant
      down-regulation of Bcl-2 expression. Along with this, a marked immunoexpression
      of p53 was also observed in these cells. Double immunolabelling study has shown
      the colocalization of Bax immunoreactivity with Bcl-2 and p53. In rats killed 1
      day after injury, a variable number of transferase d-UTP nick-end labelling
      positive cells were observed. Present findings suggest that the upregulation of
      p53 and a shift in the ratio of Bcl-2 to Bax may contribute to neuronal apoptosis
      in the CNS after closed head injury.

PMID- 10936685
TI  - Localization of flotillins in human brain and their accumulation with the
      progression of Alzheimer's disease pathology.
AB  - To clarify (1) the localization of flotillins in human brain tissue and (2) the
      relationship between senile plaque formation and flotillins localization, we
      performed Western blotting and immunohistochemical analysis. Flotillins 1 and 2
      were shown as 48 and 42 kDa bands, respectively, in human brain. The cerebral
      cortex showed a broad band-like labeling in entire layers. Flotillins were
      abundant in pyramidal neurons and astrocytes in the white matter. The intensity
      of the band-like labeling throughout the cortex became stronger with the
      development of senile plaque formation, and strongest in Alzheimer's disease.
      These findings suggest that flotillins are associated with progression of
      Alzheimer pathology.

PMID- 10936686
TI  - Effects of lanthanides on voltage-dependent potassium currents in bullfrog
      sympathetic neurons.
AB  - The effects of lanthanides (La(3+), Gd(3+), Lu(3+) and Sm(3+)) on voltage
      dependent potassium currents were studied in dissociated bullfrog sympathetic
      neurons. A-type current (I(A)) and M-type current (I(M)) were blocked by
      lanthanides (0.1-30 microM) with I(M) being much less sensitive to these ions
      than I(A). The order of potency was Gd(3+)>/=Lu(3+) approximately La(3+)
      approximately Sm(3+) for I(A) and Gd(3+)&z.Gt;Lu(3+) approximately La(3+)>Sm(3+)
      for I(M). The I(M) block occurred independently of its activation kinetics while
      the I(A) block was associated with a positive shift of the activation and
      inactivation curves. Gd(3+) (100 microM) blocked the delayed rectifier-type
      current (I(K)) by less than 20%; Lu(3+), La(3+) and Sm(3+) (100 microM for each)
      were without effect on I(K). It is concluded that I(A) was the most sensitive to
      lanthanides, and Gd(3+) was the most potent for all the currents in amphibian
      autonomic neurons.

PMID- 10936687
TI  - Mismatch negativity and behavioural discrimination in humans as a function of the
      magnitude of change in sound duration.
AB  - This study investigated how duration changes are processed in the human brain as
      indexed by the mismatch negativity (MMN), a component of the auditory event
      related potential (ERP) reflecting sensory memory. Subjects were presented with
      sequences of repetitive 100-ms white noise bursts interspersed by occasional
      duration deviants which were 1, 10, or 50 ms (decrements) or 110, 150, or 200 ms
      (increments) in duration. In a separate task, subjects were asked to detect
      deviants within the sequence via a button-press. MMN was elicited by both
      stimulus decrements and increments and increased in amplitude as a function of
      the amount of deviation from the standard duration except for the shortest, 1-ms
      deviant. Behavioural detection paralleled the MMN responses, suggesting a link
      between the processes underlying MMN and behavioural measures.

PMID- 10936688
TI  - Early-onset tolerance in rat global cerebral ischemia induced by a mitochondrial
      inhibitor.
AB  - It was studied whether a subtoxic dose of the mitochondrial neurotoxin, 3
      nitropropionic acid (3-NPA), can initiate early-onset tolerance induction for
      subsequent ischemic injury. Wistar rats were pretreated for 3 h by
      intraperitoneal 3-NPA (20 mg/kg body weight; n=13) or solvent (n=12). Fifteen
      minutes global cerebral ischemia was induced by bilateral carotid artery
      occlusion and hypobaric hypotension. rCBF and tissue hemoglobin oxygen saturation
      were measured by laser Doppler scanning and a microspectrophotometric method.
      Ischemic insult and brain temperature were identical in both groups. Body weight
      and neurological scores recovered in the pretreated group but further
      deteriorated in the non-treated group (P<0.05). Quantitative histology
      demonstrated a better neuronal density in neocortex and hippocampal CA2, CA3, and
      CA4 of pretreated animals (P<0.05).

PMID- 10936689
TI  - Acute stress decreases serotonin transporter mRNA in the raphe pontis but not in
      other raphe nuclei of the rat.
AB  - In addition to elevated corticosterone levels, stress produces structural changes
      and neuronal damage especially in the hippocampus. In this line it has been
      shown, that in rats single or repeated immobilisation markedly reduces brain
      derived neurotrophic factor (BDNF) mRNA levels in the hippocampal formation.
      Since this neurotrophin also controls the efficacy of serotonergic
      neurotransmission, the aim of the current study was to investigate the effect of
      acute immobilization stress on the expression of serotonin transporter (SERT)
      mRNA in the raphe nuclei as a parameter of serotonergic innervation. We have
      examined the expression of SERT mRNA and of BDNF mRNA in rats upon acute
      immobilisation by quantitative in situ hybridisation with a (35)S-labelled
      oligonucleotide probe. Elevated corticosterone levels in stressed animals
      confirmed as internal controls the effect of stress under our conditions. Acute
      stress led to a significant decrease of BDNF mRNA in the hippocampus and of SERT
      mRNA in the raphe pontis, but not in other raphe nuclei investigated. These data
      provide evidence for fast interactions between neurotrophins, corticosterone and
      serotonergic neurotransmission under stress conditions.

PMID- 10936690
TI  - Stimulation of synaptosomal D-[(3)H]aspartate transport by substance P in rat
      brain.
AB  - The effect of the neuropeptide, substance P, on the transport of D
      [(3)H]aspartate into rat striatal synaptosomes was studied. Almost 90% of the
      total transport of D-[(3)H]aspartate was sodium-dependent and the maximum rate
      (V(max)) of this transport was increased by 34% of control by 2.5 nM substance P
      (EC(50)=0.52 nM). In contrast, sodium-independent transport was inhibited by
      substance P. The NK(1) antagonist, L706303 (500 nM) blocked the stimulation of D
      [(3)H]aspartate transport by 2.5 nM substance P, but did not alter D-aspartate
      uptake in the absence of substance P. These results indicate that high affinity
      glutamate transporters in the brain may be under positive regulation by substance
      P, and suggest a previously-unidentified mechanism of control of glutamate
      transport.

PMID- 10936691
TI  - Examination of the human prion protein-like gene doppel for genetic
      susceptibility to sporadic and variant Creutzfeldt-Jakob disease.
AB  - A novel human gene named Doppel (DPL) that has homology to the prion protein gene
      (PRNP) has recently been identified on chromosome 20p. By automated sequencing we
      have found a common (M174T, 48%) and an uncommon coding polymorphism. The
      polymorphic frequency of the M174T allele was examined in cases of variant and
      sporadic Creutzfeldt-Jakob Disease and compared with the frequency in the normal
      UK population. In sharp distinction to the M129V polymorphism of PRNP we have not
      found any evidence of disease association nor is there any association with age
      of onset, disease duration, or prion protein (PrP(Sc)) strain type.

PMID- 10936692
TI  - Expression of mineralocorticoid and glucocorticoid receptor mRNA in the human
      hippocampus.
AB  - The genomic effects of corticosteroids in the brain are mediated through two
      receptors with a high affinity for cortisol: the glucocorticoid and
      mineralocorticoid receptor (GR/MR). We used competitive reverse transcription
      polymerase chain reaction to quantify the amount of MR and GR mRNA in hippocampal
      tissue obtained from patients with temporal lobe epilepsy. MR and GR mRNA were
      expressed at approximately the same levels as in tissues known for high
      glucocorticoid/mineralocorticoid sensitivity, i.e. liver or kidney. MR mRNA
      concentrations were significantly higher in the hippocampus of women (0.24+/-0.04
      aU, arbitrary units; mean+/-SEM) than in men (0.14+/-0.01 aU, P<0.006) or
      children (0.09+/-0.02, P<0. 007). No such differences were observed for GR mRNA
      expression.

PMID- 10936693
TI  - Expression of invariant chain and pro-cathepsin L in Alzheimer's brain.
AB  - Inflammatory and immune systems are involved in the pathogenesis of Alzheimer's
      disease (AD), but those systems in the human brain have not been well identified.
      Cathepsin L might play a predominant role in the degradation of the invariant
      chain (Ii), which plays a critical role in antigen presentation to block the
      antigen-binding site of the major histocompatibility complex class II. We
      examined the expression of Ii and pro-cathepsin L (pCPL) in AD and normal brains
      by using immunohistochemistry. Ii expresses only in resting or mildly activated
      microglia, whereas pCPL strongly expresses in fully activated microglia but not
      in resting or mildly activated microglia in AD. Normal brain tissues have rarely
      been stained for Ii or pCPL. These results suggest that the activation of
      microglia leads to expression of a complex of Ii and human leukocyte antigen
      class II at first, and that further activation, which is followed by cluster
      formation and enlargement of microglia frequently seen in the AD brain, might
      cause pCPL expression to degrade Ii. Our study confirmed that microglia plays a
      central role in the immune system of the brain, and that an activation of
      microglia is involved in the pathogenesis of AD.

PMID- 10936694
TI  - Mediation of spinal nerve injury induced tactile allodynia by descending
      facilitatory pathways in the dorsolateral funiculus in rats.
AB  - Evidence exists to indicate that tactile allodynia arising from peripheral nerve
      injury is integrated predominately at supraspinal, rather than spinal, sites. In
      the present experiments, the possibility that disruption of descending pathways
      through the dorsolateral funiculus (DLF) might alter expression of nerve-injury
      induced tactile allodynia was explored. Male, Sprague-Dawley rats received
      L(5)/L(6) spinal nerve ligation (SNL). Lesions to the DLF were made ipsilateral
      or contralateral to SNL. Tactile allodynia was determined by measuring withdrawal
      thresholds to probing with von Frey filaments. Rats with DLF lesions presented no
      apparent motor deficits and did not alter sensory threshold in sham-SNL operated
      rats. DLF lesions made ipsilateral to SNL completely blocked tactile allodynia in
      SNL rats. Contralateral DLF lesions and sham surgery did not have any effect on
      SNL-induced allodynia. These results indicate that tactile allodynia after
      peripheral nerve injury is dependent upon tonic activation of net descending
      facilitation from supraspinal sites and support the hypothesis of tonic
      activation of descending facilitation as a basis for chronic pain.

PMID- 10936695
TI  - Cross-desensitization of capsaicin-evoked oral irritation by high but not low
      concentrations of nicotine in human subjects.
AB  - We previously showed that sequential application of a relatively low nicotine
      concentration (7.4 mM) to the tongue, followed by a rest period, induced self
      desensitization, i.e. a reduction of oral irritation elicited by subsequent
      nicotine, but not cross-desensitization of capsaicin-evoked irritation. We
      presently investigated if cross-desensitization of capsaicin-evoked irritation
      might be induced by higher concentrations of nicotine. Nicotine (74 or 300 mM)
      was applied once, unilaterally to the tongue of human subjects. When the irritant
      sensation had completely subsided, capsaicin (33 microM) was applied bilaterally.
      In a 2-alternative forced-choice (2-AFC) test, subjects indicated which side of
      the tongue had a stronger irritant sensation. They additionally rated the
      intensity of irritation on each side separately. Pretreatment with 74 mM nicotine
      did not induce cross-desensitization, since no significant difference was
      observed in intensity ratings or in choice of the treated vs. non-treated side in
      the 2-AFC. However, 300 mM nicotine did induce cross-desensitization, since a
      significant majority of subjects chose the non-treated side as having a stronger
      capsaicin-evoked irritant intensity and assigned significantly higher ratings to
      that side. These psychophysical findings are discussed in terms of possible
      neural mechanisms of desensitization.

PMID- 10936696
TI  - Morphine and gabapentin decrease mechanical hyperalgesia and escape/avoidance
      behavior in a rat model of neuropathic pain.
AB  - A behavioral test paradigm that measures the aversive quality of stimulus-evoked
      pain in an animal model of neuropathic pain (L5 ligation) was tested for
      sensitivity to (1) different forces (476 and 202 mN) and frequencies (once every
      15 or 30 s) of mechanical stimulation to the hyperalgesic paw and (2) different
      doses of the common antinociceptive compounds morphine (1 and 10 mg/kg) and
      gabapentin (30 and 90 mg/kg). Compared to non-ligated controls, the greater force
      (476 mN) and frequency (every 15 s) of mechanical stimulation of the hyperalgesic
      paw was associated with the greatest degree of escape/avoidance behavior. There
      was not a significant degree of escape/avoidance behavior at the lowest force
      (202 mN) and frequency (every 30 s) of mechanical stimulation. Compared to
      ligated vehicle treated controls, morphine (1 mg/kg) and gabapentin (90 mg/kg)
      decreased mechanical hyperalgesia and also attenuated the escape/avoidance
      behavior. The antinociceptive and antiaversive effects were found at doses that
      did not produce evidence of decreased motor activity. It is concluded that the
      behavioral test paradigm used to measure the aversiveness of stimulus-evoked
      nociceptive behavior is sensitive to different degrees of evoked pain and
      traditional analgesic compounds.

PMID- 10936697
TI  - Cutaneous vascular bed is not involved in arterial pressure changes elicited by
      increasing or decreasing the activity of inhibitory vasomotor neurons in caudal
      ventrolateral medulla in rabbits.
AB  - We determined whether caudal ventrolateral medulla (CVLM) vasodepressor neurons
      tonically inhibit vasomotor tone in the ear in anesthetized rabbits. Injection of
      L-glutamate (10 nmol in 100 nl) into the CVLM decreased arterial pressure and
      increased superior mesenteric conductance. Ear conductance decreased (0.43+/-0.06
      to 0. 33+/-0.05 cm s(-1) per mmHg, n=15 injections, 12 rabbits, P<0.01).
      Conversely, bilateral injection of gamma-aminobutyric acid (100 nmol in 100 nl)
      increased arterial pressure and decreased superior mesenteric conductance. At the
      same time ear conductance increased (0.39+/-09 to 0.48+/-0.27 cm s(-1) per mmHg,
      n=8 injections, eight rabbits, P<0.05). Results suggest that ear vessels are not
      tonically inhibited by the CVLM vasodepressor neurons. Presympathetic motoneurons
      regulating cutaneous flow may be excited, rather than inhibited, by the CVLM
      neurons.

PMID- 10936698
TI  - Non-weight-bearing condition arrests the morphological and metabolic changes of
      rat soleus motoneurons during postnatal growth.
AB  - Effects of non-weight-bearing (NWB) on morphological and metabolic properties of
      motoneurons innervating the soleus muscle, a postural muscle, were studied in
      young growing rats. The soma size and the activity of succinate dehydrogenase
      (SDH), a mitochondrial enzyme, were examined after hindlimb suspension. The
      hindlimb suspension began at 21 day of age and lasted for 3 week. The results
      were compared with 21- and 42-day-old controls. The soleus motoneurons were
      identified by using a fluorescent retrograde tracer, nuclear yellow. The
      histochemical SDH activity of soleus motoneurons was not modified during the
      postnatal growth and after the NWB condition. However, postnatal increases in the
      soma size and the total SDH activity (SDH activityxsoma size) were arrested by
      the NWB condition. The results indicate that the weight support activity imposed
      on soleus motor units would be important to postnatal increases in the soma size
      and the total SDH activity (i.e. mitochondria) of soleus motoneurons.

PMID- 10936699
TI  - Expression and subcellular localization of multifunctional calmodulin-dependent
      protein kinases-I, -II and -IV are altered in rat hippocampal CA1 neurons after
      induction of long-term potentiation.
AB  - Long-term potentiation (LTP) is considered to be associated with an increase in
      expression as well as activity of Ca(2+)/calmodulin-dependent protein kinases
      (CaMKs). LTP-induced and control hippocampal slices were studied by
      immunohistochemical and electronmicroscopic analyses using anti-CaMK-I, -II and 
      IV antibodies. All three kinases were demonstrated to increase their expression
      in CA1 neurons. CaMK-I was shown to mainly localize in the cytoplasm of the
      control and LTP-induced neurons, and a significant increase of immunoreactivity
      was observed in the latter neurons. A part of CaMK-I was found to translocate to
      the nuclei of LTP-induced hippocampal CA1 neurons. Direct evidence of the
      translocation of CaMK-II from cytoplasm to nuclei in LTP was demonstrated by
      immuno-electronmicroscopy. A significant increase in expression of CaMK-IV in the
      nuclei was also observed. Our data suggest that all the three CaMKs were actively
      involved in nuclear Ca(2+)-signaling in LTP.

PMID- 10936700
TI  - No genetic association between alpha-2 macroglobulin I1000V polymorphism and
      Japanese sporadic Alzheimer's disease.
AB  - Alpha-2 macroglobulin (A2M) is a serum pan-protease inhibitor that is related
      with the pathogenesis of Alzheimer's disease (AD) through its ability to mediate
      amyloid beta degradation. Recently, it has been reported that the I1000V
      polymorphism in A2M gene might increase the risk of AD. In the present study, we
      investigated this mutation in 95 healthy controls and in 111 sporadic AD cases by
      polymerase chain reaction-restriction fragment length polymorphism method in
      order to study this hypothesis in the Japanese AD population. Allelic frequencies
      with the I1000V polymorphism in the gene were 7.4 and 6.8% in the control and AD
      groups, respectively. Our results failed to demonstrate an association between
      this polymorphism and Japanese sporadic AD, and the A2M I1000V mutation does not
      seem to be a risk factor per se for sporadic AD.

PMID- 10936736
TI  - Menopause, oestrogens and arthritis.
AB  - The menopause coincides with the appearance of many of the common arthritic
      conditions and with the lessening of severity of others such as SLE. The hormonal
      changes that occur may modulate these diseases. Thus, hormonal manipulation may
      have either beneficial or detrimental effects on the incidence and activity of a
      number of common joint diseases. We review the evidence regarding the effect of
      the menopause and oestrogen replacement therapy on the pathogenesis, incidence
      and prevalence and disease activity of osteoarthritis, rheumatoid arthritis,
      systemic lupus erythematosus and carpal tunnel syndrome.

PMID- 10936737
TI  - Hormone replacement therapy: knowledge, attitudes, self-reported use - and sales
      figures in Nordic women.
AB  - OBJECTIVES: To evaluate knowledge about, attitudes towards and use of hormone
      replacement therapy (HRT) in Norwegian women - and to compare self-reported use
      with sales statistics of HRT in the Nordic countries during recent years.
      MATERIAL AND METHODS: Random samples of Norwegian women age 16-79 were
      interviewed by the Central Bureau of Statistics in 1994 (n=737), in 1996 (n=665)
      and in 1998 (n=680). Statistics on the sale of estrogen were provided by the
      Norwegian Medical Depot and Nordic Council on Medicines. RESULTS: One in three
      women had received information about HRT during the last 2 years (1994), mainly
      through weekly magazines and physicians. The proportion answering in accordance
      with the prevailing view of HRT's effects ('correct knowledge') varied from 36.4
      to 47.2%. Those informed by a physician possessed correct knowledge, had positive
      attitudes towards HRT and were willing to use HRT more often than women informed
      through other channels. Women with a high level of education had received
      information and had correct knowledge more often than others, but they were still
      less willing to use HRT and did not use HRT more often than the less educated. In
      the age group 45-69 years the use of HRT was 16.3% in 1994, 19.1% in 1996 and 19.
      1% in 1998 (P=0.421, trend). In addition to received information, attitudes
      towards and knowledge about estrogen were the most important factors predicting
      use of HRT after adjusting for other variables. According to sales figures, the
      use of systemic estrogen in Norway has increased more than 360% since 1990.
      Although no other Nordic country has experienced a corresponding increase,
      Iceland had the highest sales figures in 1997. CONCLUSIONS: Based on the limited
      proportion of women receiving information on HRT and the ambivalence found in
      groups of educated women, we suggest that more and better information should be
      given middle-aged women to make them better able to make informed choices
      regarding use of HRT.

PMID- 10936738
TI  - Use of hormone replacement therapy: women's representations of menopause and
      beauty care practices.
AB  - OBJECTIVES: Hormone replacement therapy (HRT) during menopause has been shown to
      have beneficial effects on women's health, including preventing osteoporosis and
      probably reducing cardiovascular mortality and morbidity. However, these effects
      appear only after long use. Knowledge of factors influencing HRT use is a
      prerequisite for developing and assessing preventive actions. Most studies of
      user characteristics have focused on medical knowledge and socioeconomic
      characteristics, although social and cultural models of menopause may also play a
      role. Therefore, our study of the determinants of HRT use focused on
      representations of menopause and on beauty care. METHODS: Two scores, one
      concerning the level of beauty care and the other the representations of
      menopause, were calculated. In our population of 561 postmenopausal women from
      the GAZEL cohort in France, 409 (72.9%) had been using HRT for more than one
      year, and 152 (27.1%) had used it for less than three months, if ever.
      Associations between the study variables and HRT use were then analysed. RESULTS:
      No association was found between representations of menopause and HRT use. Beauty
      care and some beliefs about HRT (i. e. that it is useful for osteoporosis
      prevention, causes resumption of menstruation, and has anti-aging effects) were
      independently associated with HRT use. Moreover, the proportion of HRT users
      increased with socioeconomic status, with vasomotor symptoms in early menopause,
      and among hysterectomised women. CONCLUSIONS: The results suggest that the amount
      of attention women pay to beauty care plays a role, in determining HRT use.

PMID- 10936739
TI  - The influence of physical activity on the response of bone mineral density to 5
      years tibolone.
AB  - OBJECTIVES: Menopausal hormone replacement therapy (HRT) maintains bone mineral
      density (BMD) and reduces risk of fracture in postmenopausal women. It has been
      suggested that sex steroids and loading may have synergistic effects on bone. We
      therefore investigated whether habitual physical activity influences the response
      of BMD to tibolone in postmenopausal women. METHODS: The subjects were 42
      postmenopausal women aged mean (SE) 65.8+/-6.2 year who had taken tibolone for
      prevention/ treatment of osteoporosis over 5 years. Bone mineral density was
      measured annually by dual X-ray absorptiometry and physical activity was assessed
      using accelerometers after 5 years therapy. RESULTS: Twenty-six women were
      classified as having low physical activity (LPA; <15 min day(-1)) and sixteen as
      high physical activity (HPA; >15 min day(-1)). Spine BMD did not differ
      significantly between groups at baseline and increased significantly by 2 years
      of treatment with further increase to 5 years. The magnitude of increase did not
      differ between groups. Hip BMD at baseline was 7.3% higher in HPA women (P=0.07).
      Hip BMD increased over 2 years tibolone treatment in LPA women (+5.6%, P<0.01)
      whilst no significant change occurred in the HPA group (-0.5%). This difference
      in response between groups was statistically significant (P=0.002) and persisted
      after adjustment for age and body mass (P=0.002). Hip BMD was maintained in both
      groups over the subsequent 3 years of treatment. CONCLUSIONS: Spine BMD increased
      significantly in response to tibolone irrespective of physical activity
      participation. The more physically active women had higher hip BMD at baseline
      but the response to tibolone was greater in the less physically active women. The
      difference in response between groups may be due to physically active women
      having lower resorption at the hip and hence reduced response to anti-resorptive
      effects of HRT.

PMID- 10936740
TI  - Effect of estrogen replacement therapy on speed of sound at multiple skeletal
      sites.
AB  - OBJECTIVES: To evaluate the effect of estrogen replacement therapy (ERT) on
      postmenopausal bone loss by multi-site ultrasound measurement. METHODS: A cross
      sectional comparison of postmenopausal women, ERT users and non-users. The two
      study groups were enrolled for the reference database collection for the Sunlight
      Omnisense (Omnisense) and were matched by years since menopause. Speed of sound
      (SOS) was measured at the distal radius (RAD), mid-shaft tibia (TIB), fifth
      metatarsus (MTR) and proximal phalanx (PLX). RESULTS: 143 ERT users for 5.2+/-3.6
      years were compared with 139 ERT non-users (age: 57.0+/-5.3 and 57.5+/-5.5,
      respectively). Both groups were 7.1+/-5.0 years since menopause. SOS, expressed
      in T-score units, was higher at the RAD in ERT users as compared to ERT non-users
      (-0.55+/-1.30 and -1.36+/-1.60, respectively, P<0.0001), and at the TIB (-0.73+/
      1.34 and -1.28+/-1.45, respectively, P=0. 003). Same trend was observed at the
      MTR and PLX, but not statistically significant because of fewer observations. In
      early post menopause period, the ERT-non users RAD data shows an annual SOS
      decrease of 0.17 versus annual increase of 0.12 T-score units (P=0.037). Similar
      effect is observed at the TIB, though not statistically significant (non-users
      decrease of 0.20 vs. users increase of 0.08 T-score units/year, P=0.086).
      CONCLUSIONS: SOS measurements by Omnisense at multiple skeletal sites support the
      ERT protective effect on bone.

PMID- 10936741
TI  - Drug concentration effect relationship of estradiol from two matrix transdermal
      delivery systems: Menorest and Climara.
AB  - OBJECTIVES: To relate the pharmacokinetics of estradiol to pharmacological
      effects. METHODS: Drug concentration effect relationship of estradiol from two
      matrix transdermal delivery systems, Menorest and Climara, was studied in a
      single centre, open, randomised, comparative crossover study. The trial consisted
      of two treatment periods, 14 days for each patch separated by a 4-week washout
      period. Blood hormone levels were followed during the second week of each
      treatment. Estradiol levels during treatments were related to three concentration
      levels previously proposed as efficacy or safety limits. The effect of treatment
      on FSH-levels was examined and the relationship between the levels of estradiol
      and FSH was described using an inhibitory sigmoidal I(max) model. Estrone levels
      and estradiol/estrone before and during treatment were followed. RESULTS: The
      C(average) of FSH during treatment was 38% lower than baseline plasma levels.
      Estradiol had an inhibitory effect on FSH with an I(max) of 0.68 and an IC(50) of
      19 pg/ml. The fraction of time above the minimum concentration for therapeutic
      effect and the tolerability limit did not differ between the two treatments,
      whereas the fraction of time above the suggested threshold for osteoporosis
      prophylaxis was significantly larger for Menorest than for Climara (P<0.05). The
      low baseline estradiol/estrone ratios increased towards pre-menopausal levels
      during treatment. CONCLUSIONS: The drug concentration effect relationship of
      estradiol may be of use in evaluation of the effects of prophylactic estrogen
      therapy and to facilitate comparisons between different forms of estrogen
      treatments.

PMID- 10936742
TI  - Continuous-combined treatment of the menopause with combinations of oestradiol
      valerate and dienogest - a dose-ranging study.
AB  - OBJECTIVES: To determine the progestational efficacy of continuous treatment with
      various doses of dienogest, combined with oestradiol valerate, on the basis of
      endometrial histology, effect on climacteric symptoms and bleeding profile in
      postmenopausal women. METHODS: Patients were randomised to one of five fixed
      combination treatments, oestradiol valerate 2.0 mg plus dienogest 0.5, 1.0, 2.0,
      3.0 or 4.0 mg. Efficacy was assessed by endometrial biopsy, menstrual charts and
      change in climacteric symptoms. RESULTS: The endometrium was classified as
      atrophic in 20.0, 31.3, 25.0, 55.6 and 57.1% of patients in the 0.5, 1.0, 2.0,
      3.0 and 4.0 mg dienogest groups, respectively. The frequency of uterine bleeding
      was dose-dependent. The most favourable bleeding profile was seen in the 3.0 mg
      dienogest group, whereas the lower doses of dienogest had advantages with respect
      to the efficacy of the combined preparation. CONCLUSIONS: Dienogest 2.0 and 3.0
      mg are the optimal doses for combination with 2.0 mg oestradiol valerate for
      continuous-combined hormone replacement therapy.

PMID- 10936744
TI  - No colocalization of immunoreactivities for VIP and neuronal NOS, and a
      differential relation to cGMP-immunoreactivity in bovine penile smooth muscle.
AB  - The distribution of immunoreactivity (IR) for the neuropeptide vasoactive
      intestinal polypeptide (VIP) and neuronal nitric oxide synthase (nNOS) in the
      bovine retractor penis muscle (RP) and penile artery (PA) was studied by using
      two different methods. The distribution of these immunoreactivities was also
      compared with that of the immunoreactivity for cyclic guanosine monophosphate
      (cGMP). In both tissues the nerve fibers and terminals immunoreactive for VIP had
      a distribution that was completely different from that of the nerve fibers and
      terminals immunoreactive for nNOS. This contrasts with the previous observations
      in penile smooth muscle of other species. In the RP, as well as in the PA, many
      of the VIP-IR fibers were also immunoreactive for neurofilaments (NF), whereas
      the nNOS-IR fibers were consistently devoid of NF-IR. Stimulation with sodium
      nitroprusside, a nitric oxide donor, considerably increased cGMP-IR in the smooth
      muscle cells in both RP and PA, and in several nerve fibers in PA. Many of these
      cGMP-IR nerve fibers exhibited nNOS-IR, whereas none of them was immunoreactive
      for VIP. Our results suggest that the degree of coexistence of VIP-IR and nNOS-IR
      in the nerve fibers and terminals innervating penile smooth muscle show wide
      species differences. They also suggest that the mechanisms by which VIP could be
      involved in neurogenic penile erection may vary between species.

PMID- 10936743
TI  - GABA- and glycine-immunoreactive terminals contacting motoneurons in lamprey
      spinal cord.
AB  - Double postembedding GABA- and glycine-immunostaining was performed on the
      lamprey (Lampetra fluviatilis) spinal cord after previous HRP labeling of
      motoneurons. Immunopositive boutons contacting motoneurons were counted and
      distinguished as GABA (39%), glycine (30%) and both GABA+glycine-immunopositive
      (31%). Densely-packed, flattened synaptic vesicles were only observed in glycine
      immunopositive boutons while GABA-immunoreactive and GABA+glycine-immunoreactive
      boutons contained rounded or oval synaptic vesicles. Dense-core vesicles of
      different diameters were associated with conventional synaptic vesicles in 74% of
      GABA-only-immunopositive boutons, 50% of double GABA+glycine-immunopositive
      boutons, but were only observed in 9% of glycine-only-immunopositive boutons. The
      presence of terminals immunoreactive to either GABA or glycine contacting the
      motoneurons suggests that there is a morphological substrate for both GABAergic
      and glycinergic postsynaptic inhibition of motoneurons in the lamprey spinal
      cord.

PMID- 10936745
TI  - Neurochemical coding and projection patterns of gastrin-releasing peptide
      immunoreactive myenteric neurone subpopulations in the guinea-pig gastric fundus.
AB  - The aim of this study was to characterise the projection and neurochemical coding
      patterns of gastrin-releasing peptide (GRP)-containing subpopulations of
      myenteric neurones in the guinea-pig gastric fundus. For this purpose, we used
      retrograde tracing with the dye DiI and immunohistochemistry against GRP, choline
      acetyltransferase (ChAT), enkephalin (ENK), substance P (SP) and neuropeptide Y
      (NPY). Cell counts revealed that 44% of the myenteric neurones were GRP-positive.
      Of the GRP-positive neurones, 92% were ChAT-positive and, hence, 8% were
      presumptively nitric oxide synthase positive (NOS). The GRP-positive
      subpopulations were ChAT/GRP (40% of all GRP neurones), ChAT/NPY/GRP (25%),
      ChAT/SP/GRP/+/-ENK (20%), ChAT/ENK/GRP (8%), NOS/NPY/GRP/+/-ENK (5%) and NOS/GRP
      (3%). The tracing experiments revealed the relative contributions of the various
      GRP-positive subpopulations to the innervation of the circular muscle and the
      mucosa. GRP immunoreactivity was detected in 46 and 38% of the DiI-labelled
      muscle and mucosa neurones, respectively. GRP was almost exclusively found in
      ascending ChAT-positive mucosa and muscle neurones. The populations encoded
      ChAT/SP/GRP/+/-ENK and ChAT/ENK/GRP projected predominantly to the circular
      muscle, whereas the ChAT/NPY/GRP and ChAT/GRP populations had primarily
      projections to the mucosa. GRP was colocalised with ChAT, ENK and/or SP in
      varicose nerve fibres innervating the circular muscle and the muscularis mucosae,
      whereas in the mucosal epithelium GRP was mainly present in nerve fibres
      containing ChAT and NPY. The data suggest that in the guinea-pig gastric fundus,
      the ChAT/SP/GRP/+/-ENK and ChAT/ENK/GRP neurones are ascending excitatory muscle
      motor neurones, whereas the ChAT/NPY/GRP and ChAT/GRP neurones are very likely
      involved in the regulation of mucosal functions.

PMID- 10936746
TI  - Influence of light and neural circuitry on tyrosine hydroxylase phosphorylation
      in the rat retina.
AB  - Light has been shown to increase dopamine synthesis and release in vertebrate
      retinas, but the retinal circuits mediating the light signal are unknown. We
      utilized three antibodies which recognize phosphorylated forms of tyrosine
      hydroxylase (TH) at serines 19, 31, and 40 to study the effects of light and
      neuroactive drugs on TH phosphorylation in the rat retina. Phosphorylated TH and
      total TH immunoreactivities were co-localized exclusively in retinal neurons
      whose shape and location are characteristic of dopaminergic interplexiform cells.
      Phosphorylated TH was weak to absent in darkness, but light strongly stimulated
      phosphorylation in all the three serine residues. Light-induced phosphorylation
      of TH induction by light was uniformly blocked by a combination of NMDA and AMPA
      glutamate receptor antagonists. In darkness, the combination of NMDA+AMPA induced
      phosphosphorylation of TH at serines 19 and 40 but it was weak at serine 31. A
      GABA(A) antagonist had the same effect. An agonist of depolarizing (ON) bipolar
      cells, L-(+)-2-amino-4-phosphonobutyric acid, did not prevent light-induced
      phosphorylated TH formation. Carbachol, a non-specific cholinergic agonist,
      selectively induced phosphorylation of TH at serine 31 in darkness, an effect
      which was blocked by the nicotinic antagonist, d-tubocurarine. These results show
      that retinal circuits involving glutamatergic, GABAergic and cholinergic synapses
      influence phospho-TH formation at different serine residues in this enzyme. Gamma
      amino butyric acid (GABA) and glutamate influence TH phosphorylation at serines
      19 and 40, whereas cholinergic inputs affect its phosphorylation at serine 31.

PMID- 10936747
TI  - Growth of postnatal rat retina in vitro. Development of neurotransmitter systems.
AB  - In this study, we demonstrate that explanted neonatal rat retina can be
      maintained in culture for periods up to 3 weeks. The cultured retinas displayed a
      distinct layering that was almost identical to litter-matched retinas of the same
      age, but the majority of the ganglion cells did not survive and photoreceptor
      outer segments did not develop properly. Distinct synaptophysin immunoreactivity
      was expressed in both the inner and outer plexiform layers of cultured retina and
      the pattern mimicked that one observed in vivo. After 2-3 weeks in vitro, the
      inner retina expressed immunoreactivities to various components of the
      cholinergic and nitrergic transmitter systems, including nitric oxide activated
      cyclic GMP immunoreactivity. The investigated cell populations displayed similar
      distribution patterns as in situ, but morphological differences appeared in
      vitro. Such differences were mainly observed as irregularities in the
      arborization patterns in the inner part of the inner plexiform layer. We suggest
      that these discrepancies may arise as a result of reduced ganglion cell survival.
      Our observations demonstrate that some neurotransmitter systems develop in vitro
      and their neural circuitry appears similar to the in vivo situation. The presence
      of synapses, receptor proteins and transmitter substances implies that neural
      communication can occur in cultured retinas.

PMID- 10936748
TI  - AI planning and scheduling in the medical hospital environment.
AB  - Hospital management is a hard task due to the complexity of the organization, the
      costly infrastructure, the specialized services offered to different patients and
      the need for prompt reaction to emergencies. Artificial Intelligence planning and
      scheduling methods can offer substantial support to the management of hospitals,
      and help raising the standards of service. This editorial presents an overview of
      the achievements reported in therapy planning and hospital management together
      with a general roadmap of the published research in Artificial Intelligence
      planning and scheduling. Finally, a discussion for the future research and
      development in this area concludes the presentation.

PMID- 10936749
TI  - Toward interactive scheduling systems for managing medical resources.
AB  - Managers of medico-hospital facilities are facing two general problems when
      allocating resources to activities: (1) to find an agreement between several and
      contrasting requirements; (2) to manage dynamic and uncertain situations when
      constraints suddenly change over time due to medical needs. This paper describes
      the results of a research aimed at applying constraint-based scheduling
      techniques to the management of medical resources. A mixed-initiative problem
      solving approach is adopted in which a user and a decision support system
      interact to incrementally achieve a satisfactory solution to the problem. A
      running prototype is described called Interactive Scheduler which offers a set of
      functionalities for a mixed-initiative interaction to cope with the medical
      resource management. Interactive Scheduler is endowed with a representation
      schema used for describing the medical environment, a set of algorithms that
      address the specific problems of the domain, and an innovative interaction module
      that offers functionalities for the dialogue between the support system and its
      user. A particular contribution of this work is the explicit representation of
      constraint violations, and the definition of scheduling algorithms that aim at
      minimizing the amount of constraint violations in a solution.

PMID- 10936750
TI  - Continual planning and scheduling for managing patient tests in hospital
      laboratories.
AB  - Hospital laboratories perform examination tests upon patients, in order to assist
      medical diagnosis or therapy progress. Planning and scheduling patient requests
      for examination tests is a complicated problem because it concerns both
      minimization of patient stay in hospital and maximization of laboratory resources
      utilization. In the present paper, we propose an integrated patient-wise planning
      and scheduling system which supports the dynamic and continual nature of the
      problem. The proposed combination of multiagent and blackboard architecture
      allows the dynamic creation of agents that share a set of knowledge sources and a
      knowledge base to service patient test requests.

PMID- 10936751
TI  - Hybrid optimization techniques for the workshift and rest assignment of nursing
      personnel.
AB  - In this paper, a detailed model and an efficient solution methodology for the
      monthly workshift and rest assignment of hospital nursing personnel is presented.
      A model that satisfies the rules of a typical hospital environment based both on
      published research data and on local hospital requirements is designed. A hybrid
      methodology that utilizes the strengths of operations research and artificial
      intelligence was used for the solution of the problem. In particular, an
      approximate integer linear programming (ILP) model is firstly solved and its
      solution is further improved using local search techniques. Finally, a tabu
      search strategy that uses as its neighborhood the solution space that the local
      heuristics define is presented. The use of heuristics is required because one of
      the main user requirements involving the user preference for specific workstretch
      patterns is not, for efficiency reasons, explicitly modeled in the ILP. In
      addition, for comparison and evaluation purposes the CLP based ILOG solver is
      also used to solve the same problem. The inferior computational results obtained
      with the ILOG solver do verify the speed and efficiency of the hybrid solution
      approach suggested in this paper. Extensive computational results are presented
      together with a detailed discussion on the quality, the computational efficiency
      and the operational acceptability of the solutions.

PMID- 10936754
TI  - Experimental physiology in the polar regions: the historical development.

PMID- 10936755
TI  - The Irving-Scholander legacy in polar physiology.
AB  - The pioneer arctic and cold environment studies of Laurence Irving and Per
      Scholander, undertaken during the middle decades of the 20th century, have had a
      wide ranging and major influence on the direction and character of experimental
      research on polar species. Their investigations included comparative studies of
      metabolism, insulation, and acclimatization of mammals and birds in arctic Alaska
      and the tropics. Freezing, supercooling, and antifreeze research included fishes,
      insects, and plants. They examined the special problems of cooling in appendages
      of mammals and birds and the potential for acclimatization of these structures by
      repeated cold exposure. Studies of cold exposure in human populations considered
      possible adaptive reactions. Their research on diving mammals opened a vast new
      area for studies with attention to asphyxial tolerance and temperature
      regulation. A lesser-known accomplishment was an innovative approach to recovery
      of ancient atmospheric gases from polar ice fields, an approach that was
      stimulated by original investigations of frozen insect larvae and gas
      permeability through ice.

PMID- 10936756
TI  - Diving physiology of birds: a history of studies on polar species.
AB  - Our knowledge of avian diving physiology has been based primarily on research
      with polar species. Since Scholander's 1940 monograph, research has expanded from
      examination of the 'diving reflex' to studies of free-diving birds, and has
      included laboratory investigations of oxygen stores, muscle adaptations, pressure
      effects, and cardiovascular/metabolic responses to swimming exercise. Behavioral
      and energetic studies at sea have shown that common diving durations of many
      avian species exceed the calculated aerobic diving limits (ADL). Current
      physiological research is focused on factors, such as heart rate and temperature,
      which potentially affect the diving metabolic rate and duration of aerobic
      diving.

PMID- 10936757
TI  - History of polar whaling: insights into the physiology of the great whales.
AB  - The sheer size and pelagic nature of the great whales has effectively precluded
      detailed studies of most of their physiological processes. The vast majority of
      all data for these species have come from anatomical studies conducted on
      specimens that were caught in commercial and native whaling operations. In both
      the polar regions, an incredible number of whales were hunted, but anatomical
      studies were not usually conducted until relatively recent times. However, the
      anatomical data that do exist provide a valuable insight into some of the
      physiological demands placed on the animals by their marine habitat. These
      include information on blubber and nutrition; baleen and feeding ecology;
      contaminant chemistry and tissue samples; diving chemistry and acoustics. Taken
      together, these anatomical data provide the only substantial information on how
      these animals dive and hunt. Recent breakthroughs in chemical techniques however,
      are providing even greater details on function (for example, fatty acid signature
      methods). Coupled with advanced methods for tracking these whales at sea
      (acoustic and satellite), future studies should provide significant new
      information on the general physiology of these difficult to study species.

PMID- 10936758
TI  - Body size and skeletal muscle myoglobin of cetaceans: adaptations for maximizing
      dive duration.
AB  - Cetaceans exhibit an exceptionally wide range of body mass that influence both
      the capacities for oxygen storage and utilization; the balance of these factors
      is important for defining dive limits. Furthermore, myoglobin content is a key
      oxygen store in the muscle as it is many times higher in marine mammals than
      terrestrial mammals. Yet little consideration has been given to the effects of
      myoglobin content or body mass on cetacean dive capacity. To determine the
      importance of myoglobin content and body mass on cetacean diving performance, we
      measured myoglobin content of the longissimus dorsi for ten odontocete (toothed
      whales) and one mysticete (baleen whales) species ranging in body mass from 70 to
      80000 kg. The results showed that myoglobin content in cetaceans ranged from 1.81
      to 5.78 g (100 g wet muscle)(-1). Myoglobin content and body mass were both
      positively and significantly correlated to maximum dive duration in odontocetes;
      this differed from the relationship for mysticetes. Overall, the combined effects
      of body mass and myoglobin content accounts for 50% of the variation in cetacean
      diving performance. While independent analysis of the odontocetes showed that
      body mass and myoglobin content accounts for 83% of the variation in odontocete
      dive capacity.

PMID- 10936759
TI  - The role of putative glutamatergic neurons and their connections in the locomotor
      central pattern generator of the mollusk, Clione limacina.
AB  - In the pteropod mollusk Clione limacina, locomotor rhythm is produced by the
      central pattern generator (CPG), due mainly to the activity of interneurons of
      groups 7 (active in the phase of the dorsal flexion of the wings) and 8 (active
      in the phase of the ventral flexion). Each of these groups excites the neurons
      active in the same phase of the locomotor cycle, and inhibits the neurons of the
      opposite phase. In this work, the nature of connections formed by group 7
      interneurons was studied. Riluzole (2-amino-6-trifluoro-methoxybenzothiazole),
      which is known to inhibit the presynaptic release of glutamate, suppressed the
      action of the type 7 interneurons onto the follower neurons of the same and of
      the antagonistic phase of the locomotor cycle. The main pattern of rhythmic
      activity of CPG with alternation of two phases could be maintained after
      suppression of inhibitory connections from group 7 interneurons to antagonistic
      neurons. This suggests redundancy of the mechanisms controlling swimming rhythm
      generation, which ensures the reliable operation of the system.

PMID- 10936760
TI  - Decreased colonic mucus in rats with loperamide-induced constipation.
AB  - Constipation is a risk factor of colorectal cancer. Mucin is a major component of
      lumenal mucus, which protects the colorectal mucosa against mechanical and
      chemical damage. The aim of this study was to evaluate mucus production and to
      quantitate lumen mucus in a rat model of spastic constipation. We induced
      constipation with loperamide (1.5 mg/kg), and histochemically evaluated mucus
      production and the thickness of the mucus layer at the fecal surface. We
      quantitated the mucus attached to the mucosal surface using colonic perfusion
      with N-acetylcysteine. While more feces remained in the colon, there was less
      fecal excretion and lower fecal water content in loperamide-administered rats
      than in control rats. Crypt epithelial cells contained less mucus in constipated
      rats than in control rats. The mucus layer at the fecal surface was thinner and
      less mucus was recovered from the mucosal surface in constipated rats than in
      control rats. Mucus production of crypt epithelial cells and mucus at the fecal
      and mucosal surface were reduced by loperamide-induced constipation.

PMID- 10936761
TI  - Confocal imaging and timing of secretion of matrix proteins by osteoblasts
      derived from avian long bone.
AB  - Primary osteoblasts derived from avian long bone have been evaluated in terms of
      spatial and temporal expression of known osteoblastic marker proteins during the
      early phases of cell culture. Confocal imaging of matrix proteins revealed that
      osteocalcin, bone sialoprotein, osteopontin, and osteonectin were restricted to
      the cell interior at day 4 of culture; secretion and deposition into the extra
      cellular matrix of bone sialoprotein and osteopontin was evident at 8 and 12 days
      of culture. Osteocalcin and osteonectin were not deposited in the matrix within
      the timeframe of the study. Total collagen levels produced and alkaline
      phosphatase activity were substantial by day 4 of culture, and increased from
      that point 4.0- and 5.5-fold, respectively, by culture day 12. The expression of
      type I collagen, PTHrP receptor, osteopontin, bone sialoprotein and osteocalcin
      was followed by Northern blot analysis. Type I collagen and osteopontin mRNA were
      expressed at constant levels throughout the culture period. Over the 12 days of
      culture both PTH/PTHrP receptor and bone sialoprotein mRNA expression were found
      to increase by 2.3- and 2.5-fold, respectively. In contrast, the expression of
      osteocalcin message decreased by 2.5-fold by day 8 of culture.

PMID- 10936762
TI  - Respiratory responses to short term hypoxia in the snapping turtle, Chelydra
      serpentina.
AB  - Among vertebrates, turtles are able to tolerate exceptionally low oxygen
      tensions. We have investigated the compensatory mechanisms that regulate
      respiration and blood oxygen transport in snapping turtles during short exposure
      to hypoxia. Snapping turtles started to hyperventilate when oxygen levels dropped
      below 10% O(2). Total ventilation increased 1.75-fold, essentially related to an
      increase in respiration frequency. During normoxia, respiration occurred in bouts
      of four to five breaths, whereas at 5% O(2), the ventilation pattern was more
      regular with breathing bouts consisting of a single breath. The increase in the
      heart rate between breaths during hypoxia suggests that a high pulmonary blood
      flow may be maintained during non-ventilatory periods to improve arterial blood
      oxygenation. After 4 days of hypoxia at 5% O(2), hematocrit, hemoglobin
      concentration and multiplicity and intraerythrocytic organic phosphate
      concentration remained unaltered. Accordingly, oxygen binding curves at constant
      P(CO(2)) showed no changes in oxygen affinity and cooperativity. However, blood
      pH increased significantly from 7.50+/-0.05 under normoxia to 7.72+/-0.03 under
      hypoxia. The respiratory alkalosis will produce a pronounced in vivo left-shift
      of the blood oxygen dissociation curve due to the large Bohr effect and this is
      shown to be critical for arterial oxygen saturation.

PMID- 10936763
TI  - Gastrin secretion by ovine antral mucosa in vitro.
AB  - The effect on gastrin and somatostatin release in sheep of stimulatory and
      inhibitory peptides and pharmacological agents was investigated using an in vitro
      preparation of ovine antral mucosa. Carbachol stimulated gastrin release in a
      dose-dependent manner but had no effect on somatostatin release. As atropine
      blocked the effect of carbachol, cholinergic agonists appear to stimulate gastrin
      secretion directly through muscarinic receptors on the G-cell and not by
      inhibition of somatostatin secretion. Both vasoactive-intestinal peptide (VIP)
      and gastric-inhibitory peptide (GIP) increased somatostatin release but did not
      inhibit basal gastrin secretion, although VIP was effective in reducing the
      gastrin response to Gastrin-releasing peptide (GRP). Porcine and human GRP were
      stimulatory to gastrin secretion in high doses but bombesin was without effect.
      The relative insensitivity to GRP (not of ovine origin) previously reported from
      intact sheep may be caused either by a high basal release of somatostatin or by
      the ovine GRP receptor or peptide differing from those of other mammalian
      species.

PMID- 10936764
TI  - Seasonal biochemical plasticity of a flight muscle in a bat, Murina leucogaster.
AB  - Cellular and biochemical responses of the pectoral muscle to variation in
      seasonal activity were studied in the bat, Murina leucogaster ognevi. We
      collected bats in mid-hibernation (February), end-hibernation (April), and mid
      summer (August) to track major activity periods in their annual cycle. Our
      findings indicated that myofiber cross-sectional area decreased to 68% between
      mid- and end-hibernation, but returned to the winter level in mid-summer. Total
      soluble protein and total RNA concentrations were not altered over these sampling
      periods. Oxidative potential gauged by citrate synthase activity increased 1.47
      fold from mid- to end-hibernation and then remained at the similar level in mid
      summer. Glycolytic potential gauged by lactate dehydrogenase activity changed
      little between mid- and end-hibernation but increased 1.42-fold in summer,
      compared with the winter level. Thus, the myofibers underwent disuse atrophy
      during hibernation, while enzymatic catalytic function recovered towards the
      level of mid-summer.

PMID- 10936765
TI  - Effects of cumene hydroperoxide on cellular cation composition in frog kidney
      proximal tubular cells.
AB  - Effects of cumene hydroperoxide were studied on the peritubular membrane
      potential and cellular cation composition in frog kidney proximal tubular cells.
      After perfusion of isolated frog kidneys for 30 min with 1.3x10(-4) mol l(-1)
      cumene hydroperoxide Ringer solution, the peritubular membrane potential
      gradually declined. The ouabain-like effects were demonstrated on cell Na and K
      activities after 1 h of perfusion with cumene hydroperoxide. The peritubular
      apparent transference number for potassium was decreased. Intracellular pH was
      not altered in the presence of cumene hydroperoxide. Intracellular free Ca(2+)
      concentration increased slowly and moderately. The concentration of the
      malondialdehyde in the kidney homogenates, measured as an index of lipid
      peroxidation, was increased. A previously observable effect of cumene
      hydroperoxide on the peritubular membrane potential was prevented by oxygen
      radical scavengers.

PMID- 10936766
TI  - Sarcoplasmic reticulum Ca(2+)-ATPase of sea cucumber smooth muscle: regulation by
      K(+) and ATP.
AB  - Although several Ca(2+)-ATPase isoforms have been described in vertebrates,
      little is known about Ca(2+)-transport in the muscle of invertebrates. In the
      microsomal fraction obtained from the sea cucumber (Ludwigothurea grisea)
      longitudinal body wall smooth muscle, we identified a Ca(2+)-transport ATPase
      that is able to transport Ca(2+) at the expense of ATP hydrolysis. This enzyme
      has a high affinity for both Ca(2+) and ATP, an optimum pH around 7.0, and -
      different from the vertebrate sarcoplasmic reticulum Ca(2+)-ATPases isoforms so
      far described - is activated 3- to 5-fold by K(+) but not by Li(+), at all
      temperatures, Ca(2+) and ATP concentrations tested. Calcium accumulation by the
      sea cucumber microsomes is inhibited by Mg/ATP concentrations >1 mM and the
      accumulated Ca(2+) is released to the medium when the ATP concentration is raised
      from 0.1 to 4.0 mM.

PMID- 10936767
TI  - Lack of consistent hormonal responses to capture during the breeding season of
      the bearded dragon, Pogona barbata.
AB  - The bearded dragon (Pogona barbata: Agamidae) is a diurnal, oviparous, multi
      clutching lizard from Australia. We examined plasma hormonal responses to capture
      in males and females during the spring breeding season. Corticosterone
      concentrations at capture (0 h; < or =3 min after capture) were low (males:
      1.81+/-0.63 ng/ml; females 2. 23+/-0.47 ng/ml) and within sexes were unrelated to
      the time of the day, snout-vent length or, in females, reproductive condition
      (vitellogenic, gravid, assumed spent). Corticosterone concentrations at capture
      were significantly and inversely correlated with body condition in males, but not
      in females. Unexpectedly, neither sex showed significant changes in mean
      concentrations of corticosterone at 3.5 or 24 h after capture compared with 0 h
      values. Corticosterone concentrations at 3.5 h after capture did not differ
      between dragons bled at capture or not. Concentrations of progesterone in both
      the sexes did not change between 0 h and 3.5 or 24 h after capture. Testosterone
      concentrations in males at capture were moderate (10.1+/-2.2 ng/ml), and
      unchanged at 3.5 h after capture. The adrenocortical axis of adult bearded
      dragons in the breeding season seems remarkably unresponsive to capture compared
      with many other reptiles. Low adrenocortical responses to capture may be a
      feature of reptiles known to adjust well to captivity.

PMID- 10936768
TI  - Hormones and metabolites of arctic foxes (Alopex lagopus) in response to season,
      starvation and re-feeding.
AB  - Svalbard's arctic foxes experience large seasonal variations in light,
      temperature and food supply throughout the year, which may result in periods of
      starvation. The aim of this work is to investigate if there are seasonal
      variations in post-absorptive plasma thyroid hormones (free thyroxin (fT(4)),
      free triiodothyronine (fT(3)) and reverse triiodothyronine (rT(3))) and
      metabolites (free fatty-acids (FFA) and beta-hydroxybutyrate (beta-OHB)) with
      season and their response to starvation and re-feeding. The concentrations of
      post-absorptive free triiodothyronine were significantly higher in November than
      May, while those of thyroxin, reverse triiodothyronine, free fatty-acids and beta
      hydroxybutyrate remained unchanged. Possible explanations for the seasonal
      variations in free triiodothyronine are discussed. There were no significant
      changes from post-absorptive concentrations of thyroxin and reverse
      triiodothyronine in starved and re-fed foxes. However, free triiodothyronine
      concentrations decreased during starvation and increased again with re-feeding
      both in May and November. Starvation induced high levels of free fatty acids in
      both May and November, indicating increased lipolysis. There was a significant
      increase in beta-hydroxybutyrate in November only, indicating that arctic foxes
      are capable of protein conservation during starvation.

PMID- 10936770
TI  - Post-asylum geographies: an introduction.

PMID- 10936769
TI  - Body composition in mink (Mustela vison) kits during 21-42 days postpartum using
      estimates of hydrogen isotope dilution and direct carcass analysis.
AB  - We compared carcass analysis and hydrogen isotope dilution methods to measure
      total body water (TBW) and body composition in a small altricial carnivore, the
      mink. Dilution space (D) of mink at 21-42 days of age (n=20), was determined
      after subcutaneous administration of tritiated water. The same animals were then
      used to determine TBW and body composition by carcass analysis and to derive
      predictive empirical relationships between TBW and total body fat, protein and
      energy. A separate validation set of 27 kits was used to test the accuracy of
      predicting body composition from TBW. D overestimated TBW by a consistent and
      predictable 4.1% (R(2)=0.999, P<0.001). Our estimates of fat, protein and energy
      content, using equations derived from TBW, were not significantly different than
      those obtained from direct carcass analysis (P>0.980) in either the initial or
      validation set of mink. TBW was shown to decrease from 81 to 76% and total body
      protein to increase from 14 to 19% of LBM of the kits from 21 to 42 days of age.
      Although a rapidly changing hydration state was apparent in neonates, we conclude
      that when this is taken into account, accurate estimates of body composition can
      be obtained from hydrogen isotope dilution.

PMID- 10936771
TI  - From distributions of deviance to definitions of difference: past and future
      mental health geographies.
AB  - This paper reviews research in mental health geography that has examined
      landscapes of deinstitutionalisation, community care and everyday social life. It
      complements Philo's (1997, Across the water: reviewing geographical studies of
      asylums and other mental health facilities. Health and Place 3, 73-89) review of
      geographical studies concerned with asylums and other mental health facilities.
      Offering an interpretation of developments in this research sub-field, it charts
      a 'first wave' and a 'second wave' of inquiries, identifying shifts of
      substantive emphasis, theoretical approach and methodological practice. The gains
      and drawbacks of both 'waves' are discussed, with particular attention to
      absences both in what is researched and in the extent of political and policy
      engagement. The possible contours of a 'third wave' mental health geography,
      building on the strengths of earlier research but addressing new questions in new
      ways, are outlined in conclusion.

PMID- 10936772
TI  - Contracting opportunities: interpreting post-asylum geographies of mental health
      care in Auckland, New Zealand.
AB  - In New Zealand, the process of deinstitutionalization is continuing to unfold as
      a specific manifestation of welfare state restructuring rather than as a discrete
      process within the health care sector. In this paper we consider the geography of
      mental health care in Auckland, New Zealand's only metropolitan city. Here, a
      highly fluid and competitive housing market has profoundly (re)shaped the
      opportunities for community care. We report on findings from a survey of
      representatives of the key agencies providing mental health care in central
      Auckland. We argue that the re-placing of mental health care into the community
      has often involved the separation of residential and treatment issues, to the
      detriment of the communities, institutions and (especially) individuals involved.
      We trace this fragmentation back to the primacy of the ideology of restructuring
      over the philosophy of deinstitutionalization. We build our argument around a
      discussion of the Mental Health (Compulsory Assessment and Treatment) Act 1992
      and the apparent subordination of the Act to the emerging of a 'contract state'
      and broader legislation, such as the Resource Management Act 1991, the Privacy
      Act 1992 and the Commerce Act 1986, which underpins the re-regulation of New
      Zealand society.

PMID- 10936773
TI  - Mental health care reforms in Britain and Italy since 1950: a cross-national
      comparative study.
AB  - This paper discusses a cross-national comparative study, which compares the
      implementation and geographical outcomes of mental health reforms in Britain and
      Italy since 1950. Working within a cross-national framework, the research adopts
      a sensitivity to the role of place by exploring the social and spatial
      restructuring of mental health care service provision in two localities -
      Sheffield and Verona. By focusing upon the local experiences of mental health
      care reform, the research strives to gain a clearer understanding of why local
      geographies of mental health care provision appear to vary across space, both
      within national boundaries and across them.

PMID- 10936774
TI  - 'Breaking out of the asylum': developments in the geography of mental ill-health-
      the influence of the informal sector.
AB  - This paper focuses on the changing role of the voluntary sector in the provision
      of care and support to community-based individuals with mental ill-health (MIH)
      in contemporary Scotland. In doing so, it reflects on the ways in which
      deinstitutionalisation is contributing to changing interrelationships between the
      formal and informal sector, the influence of the voluntary sector in the
      development of the locational geographies of individuals with MIH, and factors
      contributing to geographical variations in access and availability of voluntary
      sector supports. These developments are considered within the framework of the
      shadow state.

PMID- 10936775
TI  - 'Building up safe havens... around the world': users' experiences of living in
      the community with mental health problems.
AB  - Deinstitutionalization moved the focus of psychiatric care away from hospital
      institutions to community settings. Mental health services are no longer driven
      by a policy of illness containment, although detention and coercion retain
      legislative and cultural legitimacy, because the conceptual and practical focus
      of caring for people in the 1990s is built around journeys to(wards) ordinary
      'independent' living. This paper draws upon the experiences of people with
      enduring mental health problems to explore the positions, roles and therapeutic
      benefits established by socio-spatial networking in the community. Social
      isolation and community integration are polar extremes, two very different
      'locations' on a 'theoretical' rehabilitation pathway shaping mental health
      policy and community care practices. The paper assesses these two locations and
      searches for the middle-ground in practice. It draws on the concept of normality
      to compare service user and professional perspectives on the rehabilitation
      process. The paper argues, with optimism, that spaces of rehabilitation are being
      found 'in the community' but notes that until mental illness is de-stigmatised
      and society celebrates difference, creating space for 'Mad Pride', the post
      asylum landscape must continue to evolve in search of models of good community
      care practice and potential landscapes of caring. The research presented in the
      paper was carried out with Rehabilitation and Community Care Services (RCCS) in
      Nottingham (1994-1997), and is based upon fieldwork observations and in-depth
      interviews with RCCS staff and 25 service users.

PMID- 10936776
TI  - Burger King, Dunkin Donuts and community mental health care.
AB  - This paper describes the patchwork of cottage industries and human warehousing
      composing Montreal's 'community mental health care' system. It examines the ways
      in which this system's clients assemble a collage of ad hoc facilities including
      homeless shelters, rooming houses, food banks and soup kitchens through which
      they pursue the fragmented task of daily survival. In their various forms of
      transit around the city, released psychiatric patients, who rotate in and out of
      the local psychiatric wards, construe the grammar of urban space. In examining
      their use of key city sites - malls, fast food outlets, churches and the streets 
      it becomes apparent that the 'mad' have a particular relationship to these
      places which they pass through and use on certain terms. Examining the nature of
      their journeys, the scenes on which they are set and the social relationships of
      space in play, it is evident that the 'mad' have a particular (dialogical)
      relationship to the city: a relationship which they share with other, multiply
      disenfranchised people. This raises significant social questions concerning the
      politics of city space, and the kinds of fragmented lives and forms of
      subjectivity that they produce.

PMID- 10936777
TI  - Interpreting the 'hidden social geographies' of mental health: ethnographies of
      inclusion and exclusion in semi-institutional places.
AB  - This paper critically evaluates, through use of covert ethnographic materials, an
      inner-city drop-in as a semi-institutional place where the identities of people
      with mental health problems are influenced by social processes of inclusion and
      exclusion. It is demonstrated, through an in-depth interpretative approach, that
      it is possible to understand more about the micro-geographies which make up
      deinstitutionalized landscapes, and about the social relations which characterise
      these. Key to this paper are findings which indicate that people with mental
      health problems cannot be understood as a straightforwardly homogeneous
      'excluded' grouping, and that mainstream processes of boundary maintenance are in
      operation among these constructed 'others'.

PMID- 10936778
TI  - Risk and protection: the discourse of confinement in contemporary mental health
      policy.
AB  - Confinement has regained respectability in the discourses of contemporary UK
      mental health policy. This development reflects concern about violent offences by
      people with mental health problems and is rooted in claims about the 'failure' of
      community care. Confinement is presented as a strategic response to the risks and
      dangers posed by particular fractions of the population of mental health service
      users. Using two key policy statements issued by the Department of Health and
      associated discussions in the health services management press, the confinement
      theme is explored and assessed. The paper notes its emergence as a consequence of
      the spatial impacts of deinstitutionalization and its specific origins in
      response to violent offences by people with mental health problems. The notion
      that the growing emphasis on confinement presages a return to the asylum is
      considered and rejected. Rather, the paper stresses the importance of discourses
      of protection, safety, risk and dangerousness in understanding the turn to
      confinement.

PMID- 10936779
TI  - Many years on...when afar and asunder?

PMID- 10936780
TI  - Asylum and post-asylum geographies after twenty-five years.

PMID- 10936781
TI  - Tumor sinuses- vascular channels.
AB  - The existence of tumor cell-lined sinuses (vascular channels) in various
      experimental and human cancer is known for almost a half a century described by a
      Hungarian pathologist, Bela Kellner. Meanwhile, even the existence as well as the
      pathomechanism and the possible functional significance of these sinuses are
      heavily challenged in the recent literature. Ultrastructural studies however
      provide evidence for the presence of tumor cell-lined sinuses in human melanoma
      and breast cancer. The generation of such sinuses can be suggested in two ways:
      by de novoformation, when tumor cells recapitulate an embryonic geno- and
      phenotype by reexpressing endothelial genes or by a secondary mechanism, where
      the incorporated microvessels degenerate due to the predominant expression of
      anti-angiogenic factors. Literature data are available for the potential
      diagnostic and clinical significance of the tumor sinuses (vascular channels)
      stimulating further studies on this issue.

PMID- 10936782
TI  - Detection and isolation of MUC1 mucin from larynx squamous cell carcinoma.
AB  - The progression from uncontrolled cell proliferation to invasion and metastasis
      of epithelial tumors is partially understood. Alteration of epithelial mucin
      expression have been described in different malignant localizations but only few
      attempts have been made to identify mucin expression in malignant laryngeal
      tumors. In the present report, results are shown of studies on the expression of
      mucins and carbohydrate related antigens in laryngeal cancer and on the isolation
      of MUC1 mucin from this tumor tissue. Malignant laryngeal specimens were
      processed for immunohistochemical analysis and for extranuclear membrane
      fractions (ENM) which were obtained by ultracentrifugation. Subsequently, ENM
      samples were centrifuged in density-gradient; the analysis of fractions was
      performed by means of SDS-PAGE and Western-blotting. The panel of monoclonal
      antibodies (MAbs) included anti MUC1 mucin, anti Lewis x, anti sialyl Lewis x,
      anti Lewis y, anti MUC-5B, anti oral mucin (gp230), anti Tn hapten, anti p53 and
      anti cytokeratins. By immunohistochemistry, it was possible to detect MUC1 mucin,
      Lewis x and Lewis y showing strong reactions while sialyl-Lewis x and Tn antigen
      only reacted weakly in a few cells; cytokeratins were detected in all samples. In
      ENM derived fractions obtained by CsCl centrifugation, MUC1 was demonstrated by
      Western blotting. CONCLUSIONS: (1) laryngeal cancer antigenic expression
      comprises mostly MUC1 mucin, Lewis x, Lewis y as well as Tn antigen and (2) the
      methodology here employed is useful to isolate MUC1 from tumor samples.

PMID- 10936783
TI  - Moc-31, fibronectin and CEA in the differential diagnosis of malignant effusions:
      an immunocytochemical study.
AB  - In discriminating benign and malignant origins of cytologically suspicious
      effusion smears a panel of antibodies against carcinoembryonic antigen (CEA),
      Fibronectin (F) and MOC-31 was used with immuno-cytochemical techniques. One
      hundred and thirty seven effusions were studied of which 107 had a malignant and
      30 a benign aetiology as determined by clinical and histological examination.
      Cytologically 24 were diagnosed as benign, 97 as malignant and 14 as suspicious.
      Staining for F was positive in all effusions of benign and 3 of malignant origin.
      MOC-31 was positive in 95 (88.8%) of effusions of malignant origin but none of
      benign origin. Positive CEA was observed in 43% of effusions of malignant origin
      and in 10 of benign origin. The combination of MOC-31 positivity measured the
      sensitivity and specificity of the cytological examination in cases where the
      cytological examination result was suspicious as did F positivity improve the
      sensitivity for a benign origin of the effusion. Positivity or negativity for CEA
      is less valuable than the other parameters.

PMID- 10936785
TI  - Improving diagnostic accuracy of prostate carcinoma by systematic random map
      biopsy.
AB  - Systematic random rectal ultrasound directed map-biopsy of the prostate was
      performed in 77 RDE (rectal digital examination) positive and 25 RDE negative
      cases, if applicable. Hypoechoic areas were found in 30% of RDE positive and in
      16% of RDE negative cases. The score for carcinoma in the hypoechoic areas was
      6.5% in RDE positive and 0% in RDE negative cases, whereas systematic map biopsy
      detected 62% carcinomas in RDE positive, and 16% carcinomas in RDE negative
      patients. The probability of positive diagnosis of prostate carcinoma increased
      in parallel with the number of biopsy samples/case. The importance of systematic
      map biopsy is emphasized.

PMID- 10936784
TI  - Alkaline phosphatase histochemistry and biochemistry in the diagnosis of complete
      hydatidiform mole.
AB  - The purpose of this study was a complementary method to the diagnosis and
      prognosis of complete hydatidiform mole (CHM) and differentiate it from the other
      cases of gestational trophoblatic diseases. This was done by examining the
      quality and quantity of the total and the placental alkaline phosphatase
      activity. The ALP in the tissues and sera from 12 patients were compared with 13
      control normal non-pregnant and 30 control pregnant females. The enzyme
      activities were determined by biochemical and histochemical examination. The
      placental tissues were obtained from uterine curettage, or after delivery which
      then were frozen in a liquid nitrogen and processed for biochemical study.
      Cryosections were histochemically stained for ALP and PLAP by the azo coupling
      method. Isoenzyme specificity was evaluated by heating the tissue at 65 degrees C
      for 15 min while the including L-phenylalanine (50 mM), D-phenylalanine (50 mM)
      and L-homoarginine (50 mM) were used for chemical inhibition study. The activity
      of ALP and PLAP of patients were reduced in comparison with pregnant control
      group (P<0.05). There was no significant difference between the patients and non
      pregnant control (P<0.05) group. The localization of enzyme activities in
      cryosections of all groups were in the basal, apical, and the cytoplasm of
      syncytiotrophoblast cells. The ALP in all the groups was thermostable (65 degrees
      C for 15 min) and was inhibited by L-phenylalanine, but no inhibition was seen
      with L homoarginine in patients group only. These findings suggest that the PLAP
      is a useful marker in the diagnosis and prognosis of hydatidiform mole.

PMID- 10936786
TI  - Intra-tumoral cytolytic cells: pattern of distribution in B-cell non Hodgkin s
      lymphoma.
AB  - Non-Hodgkin s lymphomas (NHLs) constitute a heterogeneous group of lymphoid
      neoplasms and a majority of them in India are of B-cell phenotype. Varying
      numbers of T lymphocytes and natural killer (NK) cells are consistently present
      within the lymph nodes (LNs). The role of these reactive cells is becoming
      understood. TIA-1 is a cytotoxic granule associated RNA binding protein, the
      expression of which is restricted to cytotoxic T lymphocytes (CTLs) and NK cells.
      Snap frozen lymph node biopsies obtained from 41 B-cell NHLs were localized for
      intra-tumoral TIA-1 + cytolytic cells by immunohistochemistry. Distribution of T
      cell subsets and NK cells were also quantified. Cells expressing TIA-1 antigen
      was observed in all the cases, seen as a strong granular cytoplasmic signal.
      Results indicate significantly higher number of TIA-1 cytolytic cells outside
      (periphery of the follicle and interfollicular areas) than within the neoplastic
      follicle in follicular lymphomas (p<0.001). In small lymphocytic lymphomas,
      cytolytic cells were mainly seen as uniformly scattered single cells, distributed
      throughout the tumor environment. In mantle cell and diffuse large B-cell
      lymphomas these were most often seen as small clusters and less frequently as
      singly scattered cells. Higher numbers of CD4 + than the CD8 + T cells were
      observed in most cases. Contrary to the follicles in follicular hyperplasia, CD57
      + NK cells were predominantly observed outside the neoplastic follicle in
      follicular lymphomas (FLs). These results outline specific interactions between
      the potential anti-tumoral cytolytic and the malignant cells of B-cell NHLs.

PMID- 10936787
TI  - The distribution of extracellular matrix proteins and CD44S expression in human
      astrocytomas.
AB  - Aims of the study were: 1. to establish the prevalence of CD44 protein expression
      in human astrocytomas; 2. to compare the distribution of the extracellular matrix
      in these tumors; 3. to investigate the relation between CD 44, the extracellular
      matrix proteins and the histological grade of the tumor. CD44, Type IV Collagen
      (Col IV), Laminin (LN), Fibronectin (FN), and Tenascin (TN) expression were
      detected by immunohistochemistry in formalin fixed paraffin embedded tissue
      samples of 52 astrocytic tumors: 35 glioblastomas (GB), 7 Anaplastic astrocytomas
      (AA) and 10 astrocytomas (A). The localization of Col IV was observed in the
      basement membrane of the vessel walls in most of the astrocytomas (88.4%) with a
      similar pattern obtained with LN staining. 7 of 10 A (70%), 2 of 7 AA (28%) and 9
      of 35 GB (25.7%) showed LN positivity. There was a negative correlation between
      LN expression and tumor grade (p=0.03). FN was either localized in the basement
      membrane or showed thick multi-layered immunoreactivity of the vessel walls. FN
      expression was seen in 6 A (60%), 4 AA (57%) and all of 35 GB (100%). The FN
      distribution was not uniform and its staining intensity showed decrease in GB. 3A
      (30%), 3 AA (42%), 27 GB (77.1%) showed TN expression in the vessel walls and in
      some tumor cells of 19 GBs. TN expression was positively correlated with the
      degree of vascular endothelial proliferation in GB (p<0.05). The expression of
      CD44s wasseen as plasma membrane positivity of glioma cells in 5 of 10A (50%), 3
      of 7AA (42.3%) and 29 of 35 GB (82.8%). The intensity of immunoreaction was quite
      strong especially near the vessels. There was a good correlation between TN and
      CD44s expression in human astrocytic tumors (p=0.005). No relationship was
      observed between GFAP, ECM proteins and CD44s expression. Both CD44s and TN
      expression showed increase with malignancy in astrocytomas. These findings
      indicated that the histological malignancy of the astrocytomas was correlated
      with expression of TN and CD44s. It was suggested that in astrocytomas there was
      a biological relationship only between CD44 and TN, but none with the other ECM
      proteins. TN may play a role in angiogenesis in human astrocytic tumors.

PMID- 10936788
TI  - Pre-existing histological type and developmental mechanism of mucinous noncystic
      carcinoma of pancreas.
AB  - Eleven cases with mucinous noncystic carcinoma (MC) of the pancreas were studied
      by histology and mucin immunohistochemistry, to elucidate the mechanism, or route
      of development, and pre-existing histological type of MC of the pancreas. These
      MCs were observed in close approximation to, or surrounding, intraductal
      papillary-mucinous carcinomas (IPMCs), and were centrally situated among ductal
      adenocarcinomas (DAs). Hence, the 11 cases originated from 8 IPMCs and 3 DAs. The
      mechanism and routes to MC were divided into four types as follows: IPMC directly
      invaded the stroma (4 cases), over-production of mucin in IPMC expanded the
      branches of the pancreatic duct possibly resulting in rupture (3 cases), DA
      underwent extreme mucinous degeneration (3 cases), and a recurrent form, as MC,
      at the surgical stump of IPMC (one case). The outcomes of MC cases with IPMC had
      variable survival rates, while those from DA had short durations. MUC
      immunoreactivity in MC was divided into three categories; anti-MUC1-positive only
      (2 IPMCs, 2 DAs), mixed anti-MUC1 and anti-MUC2-positive (3 IPMCs, one DA) and
      anti-MUC-positive only (3 IPMCs). Pre-existing MC histological types included
      both IPMC and DA. These two pre-existing types of MC involved mucin
      overproduction and mucinous degeneration. MUC immunoreactivity in MC revealed
      three patterns, which may be related to variable outcomes.

PMID- 10936789
TI  - Apoptosis-related proteins, BCL-2, BAX, FAS, FAS-L and PCNA in liver biopsies of
      patients with chronic hepatitis B virus infection.
AB  - While the elimination of hepatitis B virus (HBV) is a common phenomenon at the
      end of the acute phase of disease, the persistence of HBV is characteristic for
      chronic hepatitis (CHB). Recent evidence indicates that the elimination of HBV is
      achieved by FAS/FAS-L induced apoptosis of infected hepatocytes. The aim of this
      study was to test the hypothesis that HBV persistence in the hepatocytes of CHB
      patients is due to the delayed onset of apoptosis caused by altered FAS/FAS-L
      interactions between lymphocytes and hepatocytes. The expression of FAS, FAS-L,
      BAX, BCL-2, ICE and PCNA in the liver biopsies of 55 patients (14 HBsAg positive,
      20 patients with alcoholic hepatopathy, 21 patients with other hepatopathies) was
      tested by immunohistochemistry. Apoptosis of hepatocytes was evaluated by
      morphological as well as by TUNEL method. The results were correlated with a
      grading/staging score and analysed statistically using a one way analysis of
      variance and the Duncan test. Significantly highernumbers of BAX positive
      hepatocytes were observed in HBsAg positive patients when compared to control
      groups. Similarly, both BAX and FAS positive lymphocytes were more frequent in
      HBsAg positive patients. FAS-L positive lymphocytes and hepatocytes were numerous
      in all patient groups. Increased numbers of BAX positive hepatocytes in CHB may
      reflect the increased readiness of these cells to undergo apoptosis. However, the
      increased numbers of both BAX and FAS positive lymphocytes in CHB suggest that
      these cells may be particularly sensitive to FAS-L mediated apoptosis potentially
      resulting in lowered viability of these lymphocytes. This may explain, at least
      in part, the defective removal of virus-infected cells in chronic hepatitis.
      However, we cannot rule out the possibility that survival of hepatocytes during
      CHB may be due to other mechanisms such as defects in apoptosis activation
      triggered by CD40, defects involving DNase and/or other caspases downstream in
      the apoptotic cascade within these cells, or to defects in CTL function.

PMID- 10936791
TI  - New human Dirofilarioses in Hungary.
AB  - About ten cases of filariosis have recently been recorded in the Hungarian
      medical literature, six of them caused by Dirofilaria repens. Dirofilaria
      repensis a mosquito-transmitted filaroid worm in the subcutaneous tissue of dogs
      and cats in the temperate areas of the Old World. It accidentally infects man,
      too, and can remain unidentified due to physicians, poor knowledge of the
      parasite. In the last two years six new Dirofilaria repensinfections have been
      found in various parts of the country: five localised dermally and one in the
      deep tissues. Two of the cases might have been acquired in Italy during summer
      travels. Four patients, however, have never been abroad, these cases must be
      considered autochtonous infections. The thickness of the multilayered cuticle of
      the worm, diameter of the body and the size, form and number of the longitudinal
      ridges on its surface are used in the histological diagnosis of the the parasite.

PMID- 10936790
TI  - Ependymoma with extensive lipidization mimicking adipose tissue: a report of five
      cases.
AB  - Lipomatous ependymoma is a recently described entity and only 3 cases of this
      variant have been reported in the literature. We report 5 cases of this rare
      variant of ependymoma. Patients age ranged from 4 years to 45 years and,
      interestingly, all of them were males. Two tumors were supratentorial in
      location, 2 in the fourth ventricle and 1 was intramedullary. Microscopically all
      of them showed the classical histology of ependymoma along with lipomatous
      differentiation. The lipomatous component was composed of cells with a large
      clear vacuole pushing the nucleus to the periphery and giving a signet ring cell
      appearance. This component demonstrated positivity for GFAP and S-100 protein
      thereby confirming its glial lineage. Three of the 5 tumors were high grade (WHO
      grade III), had a high MIB-1 labelling index (MIB-1 LI) and showed recurrence on
      follow-up. However, 2 were low grade (WHO grade II) and patients are free of
      disease till the last follow up.

PMID- 10936792
TI  - Cystic lymphangioma of the small-bowel mesentery: case report and a review of the
      literature.
AB  - Cystic lymphangioma of the small-bowel mesentery is a rare manifestation of an
      intraabdominal tumor in elderly patients. We present a case of a small-bowel
      mesentery lymphangioma, causing fever and chills and present clinical and
      pathologic features. Furthermore, etiology and differential diagnosis of this
      tumor are discussed.

PMID- 10936793
TI  - Pathology in the new medical curriculum: what has replaced the subject courses?
AB  - In line with the UK General Medical Council recommendations, the traditional,
      taught curriculum at Liverpool was replaced from 1996 by a new one using problem
      based learning (PBL) as its principal method of information transfer. There is
      integration of clinical and preclinical studies, coupled with a reduction in the
      factual knowledge content and the disappearance of identifiable separate subject
      courses. Learning is now student-centred. This requires a new approach to the
      acquisition of pathology knowledge. 1. Pathology is included in all relevant PBL
      case scenarios by pathology representation on module planning and review
      committees. 2. Special study modules (SSMs) allow students to observe the
      practice of pathology including surgical and autopsy work, carry out a detailed
      study and write a dissertation. Career selectives are provided for individual
      students in the final year. 3. Clinicopathological (CPC) teaching meetings are
      held, with the discussion of case examples, clinicians and students contributing.
      4. Assessments include the input of appropriate pathology content, integrated
      with other subjects. 5. A pathology teaching website is provided, containing
      images, notes, self-assessment questions, handouts, timetables and information.
      Although the 1996 intake have not yet completed their studies, the results of in
      course assessments have been encouraging. The response to the pathology SSMs has
      been very positive, and the level of presentations and dissertations reached is
      of a high standard. With the disappearance of a separate subject course in
      pathology, the subject is being learned by other routes, and the students will
      complete their undergraduate course with a sound basis for proceeding with their
      further studies.

PMID- 10936795
TI  - Whither goest Kt/V?
AB  - Uremia is characterized by gross contamination of body water with a wide spectrum
      of retained solutes normally excreted by the kidney. The rationale for dialysis
      therapy is that these retained solutes have concentration-dependent toxicity,
      which can be ameliorated through removal by dialysis. Apart from the well
      established clinical consequences of abnormalities in fluid, electrolyte, acid
      base metabolism, and retained beta 2-microglobulin (beta 2 m), there is very
      little understanding of solute-specific uremic toxicity. Evidence is reviewed to
      demonstrate the following: (1) Many aspects of the uremic syndrome are controlled
      by adequate dialysis of low molecular weight solutes. (2) Urea can serve as a
      generic molecule to quantitate the fractional clearance of body water by dialysis
      (Kt/V) of retained low molecular weight solutes. (3) Urea has no concentration
      dependent toxicity, and the generation rate of putative toxic low molecular
      weight solutes is not proportional to urea generation. The major clinical
      consequences and controversies stemming from these interrelationships are
      reviewed. Kinetic approaches to determine Kt/V dose equivalency between
      intermittent and continuous dialysis therapy are reviewed. We conclude that Kt/V
      can and will be generalized to describe the kinetics of other solutes such as
      beta2m as our knowledge of uremic toxicity grows, and hence, it is predicted that
      it will goeth and goeth and goeth.

PMID- 10936796
TI  - Confounding factors in the assessment of delivered hemodialysis dose.
AB  - A satisfactory dialysis patient's outcome results from an effective and
      personalized therapy. However, the higher the prescribed efficiency, the more
      likely it is that the prescribed dose is incorrectly administered. Avoiding
      discrepancies between the prescribed and delivered doses calls for a continuous
      surveillance, from urea kinetics to urea biosensors. An unexpectedly low
      efficiency result may affect several patients or may just be limited to the
      individual patient. An inadequate calibration of blood and dialysate pumps or
      manufacturing defects in blood tubings or needles may be responsible for a more
      diffuse phenomenon. The most frequently detected factors in the individual
      patient are poor vascular access, recirculation, decreases in dialyzer
      performance and insufficient anticoagulation. However, urea removal per se is not
      enough to satisfy all the assumptions underlying an adequate dialysis therapy.
      Indeed, dialysis adequacy is achieved by way of a complex combination of numerous
      elements transcending urea removal alone: acidosis correction, the achievement of
      dry body weight, fluid and electrolyte homeostasis, good blood pressure control,
      overall biocompatibility, anemia and malnutrition correction, and finally, a
      customized schedule together with treatment duration.

PMID- 10936797
TI  - Urea as a marker of adequacy in hemodialysis: lesson from in vivo urea dynamics
      monitoring.
AB  - BACKGROUND: "Dialysis dose," a concept developed by Sargent and Gotch based on
      urea kinetic modeling, is a useful and recognized tool that is used to quantitate
      and optimize a dialysis-efficacy program. However, it has been shown that
      oversimplification of the "dialysis adequacy" concept to the Kt/V index might
      lead to dramatic underdialysis and subsequent deleterious consequences on
      morbidity and mortality of dialysis patients. With this perspective, the
      determination of Kt/V must be very cautious and rely on accurate measurement of
      postdialysis urea concentration and its use integrated as a tool in a quality
      assurance process. METHODS: In this study, we analyzed urea dynamics by means of
      a blood side (ultrafiltrate) continuous online urea monitoring system interfaced
      with a two-pool model hosted in a microcomputer. The study was designed to
      provide instantaneous dialysis performances (body and dialyzer clearances,
      dialyzer mass transfer coefficient) and to determine the in vivo functional
      permeability characteristics of the patient [intercompartment urea mass transfer
      coefficient (Kc)]. Thirteen end-stage renal disease patients (age 54 +/- 16
      years; 12 male and 1 female) were studied during nine consecutive dialysis
      sessions (3 weeks). RESULTS: Urea kinetics obtained from the urea monitoring
      system fitted closely the urea kinetic modeling prediction, confirming the
      validity of the double-pool model structure. Effective in vivo urea mass transfer
      coefficient averaged 912 +/- 235 mL/min/1.73 m2, a value close to those reported
      with more invasive methods. Large variations ranging from 363 to 1249 mL/min were
      observed among patients, confirming very large interindividual patient
      permeability differences. Interestingly, the urea mass transfer coefficient was
      inversely correlated with the postdialysis rebound values. Intraindividual
      variations were also noted as a function of time denoting functional changes in
      urea mass transfer coefficient values. The urea distribution volume was 38.1 +/-
      7, 8 L (53 +/- 8% body weight). V1 referring to the extracellular volume and V2
      to the intracellular volume were 9 +/- 2 L (13 +/- 2% body weight) and 29.2 +/-
      6.6 L (41 +/- 1.3% body wt), respectively. The extracellular/intracellular volume
      ratio was 0.31 (approximately one third) and was not as usually defined by the
      paradigm 1/2 ratio. CONCLUSION: Online double-pool urea kinetic modeling gave a
      new insight in urea kinetic modeling approach. Urea dynamics fit perfectly a
      double-compartment model structure. Accessible extracellular volume to
      hemodialysis is smaller than expected. The in vivo urea mass transfer coefficient
      must be considered as an individual and variable characteristic of ESRD patients
      that should be taken into consideration when prescribing the hemodialysis
      schedule.

PMID- 10936798
TI  - Adequacy in hemodialysis: new concepts derived from online urea monitoring.
AB  - BACKGROUND: The estimation of urea kinetic parameters [urea generation rate (Gu),
      normalized protein catabolic rate (NPCR), and dialysis dose (Kt/V)] is routinely
      performed during a single hemodialysis session as a representative sample of a
      stable series. To ascertain whether the stability assumption is tenable and to
      estimate the variability of urea kinetic parameters, a number of stable patients
      on regular dialysis treatment in their usual clinical setting were followed.
      METHODS: Thirteen stable patients on regular hemodialysis aged 61 +/- 11 were
      monitored from 5 to 24 weeks (median, 10 weeks) with the urea biosensor system in
      double-chamber hemodiafiltration. Body weight did not change appreciably.
      Residual renal function was negligible or absent. Weekly averaged urea
      concentration (TACw), Gu, NPCR, and Kt/Veq were calculated, and their serial
      patterns and interrelationships were evaluated through graphical analysis and
      linear regression. RESULTS: In six patients, the urea pool was substantially
      unchanged, but variability of Gu and Kt/V was comparable to that of the other
      groups. In three patients, body urea pool increased. Gu went from 4. 78 +/- 0.44
      to 5.40 +/- 0.65 mg/min, and Kt/V went from 1.25 +/- 0. 25 to 1.34 +/- 0.31. In
      four patients, body urea pool decreased; Gu went from to 6.55 +/- 1.91 to 5.85 +/
      2.26 mg/min, and Kt/V did not change appreciably. Parameters might change in a
      nearly linear trend or occasionally as abrupt or oscillating phases. Gu was the
      main factor involved, and the only one affecting four of the seven unstable
      patients. Kt/V was never solely involved. CONCLUSIONS: Our data indicate that the
      estimation of urea kinetic parameters is often affected by a non-negligible
      degree of variability, which can be ascribed to the variability of the dialytic
      dose delivered and, above all, to the daily changes of diet protein assumption.

PMID- 10936799
TI  - The removal of uremic toxins.
AB  - Three major groups of uremic solutes can be characterized: the small water
      soluble compounds, the middle molecules, and the protein-bound compounds. Whereas
      small water-soluble compounds are quite easily removed by conventional
      hemodialysis, this is not the case for many other molecules with different
      physicochemical characteristics. Continuous ambulatory peritoneal dialysis (CAPD)
      is often characterized by better removal of those compounds. Urea and creatinine
      are small water-soluble compounds and the most current markers of retention and
      removal, but they do not exert much toxicity. This is also the case for many
      other small water-soluble compounds. Removal pattern by dialysis of urea and
      creatinine is markedly different from that of many other uremic solutes with
      proven toxicity. Whereas middle molecules are removed better by dialyzers
      containing membranes with a larger pore size, it is not clear whether this
      removal is sufficient to prevent the related complications. Larger pore size has
      virtually no effect on the removal of protein-bound toxins. Therefore, at
      present, the current dialytic methods do not offer many possibilities to remove
      protein-bound compounds. Nutritional and environmental factors as well as the
      residual renal function may influence the concentration of uremic toxins in the
      body fluids.

PMID- 10936800
TI  - Adsorption in hemodialysis.
AB  - The use of sorbents in different blood purification techniques is reviewed. The
      sorbents used in these therapies are divided into two groups: (1) Adsorption
      occurs fundamentally because of the hydrophobic properties of the sorbents. In
      this group, the sorbents used in different dialysis techniques are charcoal and
      nonionic macroporous resins. (2) Adsorption occurs by chemical affinity, such as
      ion exchange resins and chemisorbents. Sorbents were initially used in
      hemoperfusion, which caused many adverse events; later, with the use of coated
      charcoal, these undesired effects decreased or disappeared, but the adsorptive
      properties, water control, and acid-base balance still created problems. For
      these reasons, the use of sorbents in the treatment of chronic renal failure was
      almost totally discontinued. Little by little, interest in these substances has
      reappeared, and at present, they have been used in combination with other blood
      purification techniques such as hemodialysis, hemofiltration, peritoneal
      dialysis, and finally, hemodiafiltration. Within the various hemodiafiltration
      techniques, paired filtration dialysis-charcoal is being used to regenerate the
      ultrafiltrate, which is used as the replacement fluid. Charcoal regenerates the
      ultrafiltrate and transforms it into a physiological solution with a normal
      electrolyte composition, calcium, bicarbonate, and glucose, having eliminated the
      majority of both middle and large molecule uremic toxins. If regeneration is done
      properly, this replacement fluid is bacteria and endotoxin free. Studies
      currently are underway on the adsorption of different inflammatory substances in
      the ultrafiltrate, which could lead to improvement in the biocompatibility of the
      system.

PMID- 10936801
TI  - Hemodiafiltration with online regeneration of the ultrafiltrate.
AB  - The concept of regeneration of dialysis fluids and of ultrafiltrate in particular
      has been recently revisited. Hemodiafiltration with online regeneration of the
      ultrafiltrate allows the concomitant infusion of sodium, calcium, and
      bicarbonate. Here, we studied the adsorptive characteristics of an integrated two
      step sorbent system relative to different solutes present in the ultrafiltrate:
      sodium, calcium, phosphate, bicarbonate, uric acid, creatinine, and beta2
      microglobulin. In vitro studies were performed in order to differentiate the
      relative roles for each sorbent (mineral-activated charcoal or hydrophobic resin)
      in adsorbing a given solute. Ex vivo studies were performed in order to evaluate
      the presence of cytokines (interleukin-1 beta and tumor necrosis factor-alpha),
      of cytokine (interleukin-1 beta and tumor necrosis factor-alpha)-inducing
      activities, and of the cytokine release in response to exogenous bacterial
      lipopolysaccharide by normal whole blood incubated with ultrafiltrate samples
      obtained at 15, 120, and 240 minutes after the start of treatment. The results of
      the present studies show the presence of immunomodulatory substances in the
      ultrafiltrate and the significant (P < 0.01) increase in the lipopolysaccharide
      induced release of both interleukin-1 beta and tumor necrosis factor-alpha. The
      biological relevance of the ultrafiltrate and the possible relevance of the
      online, endogenous reinfusion are discussed.

PMID- 10936802
TI  - Role of sodium in hemodialysis.
AB  - Sodium chloride is the most abundant salt in extracellular fluid. In normal
      individuals, the tonicity exerted by dissolved sodium chloride determines plasma
      osmolality and indirectly determines intracellular tonicity and cell volume.
      Uremic patients retain nitrogenous wastes and have an elevated plasma osmolality.
      While urea exhibits osmotic activity in serum, no sustained gradient can be
      established across cell boundaries because it readily diffuses through cell
      membranes. Thus, sodium remains the major indicator of body tonicity and
      determines the distribution of water across the intracellular-extracellular
      boundary, subsequent cell volume, thirst, and, among patients with renal
      insufficiency, systemic blood pressure. As a result of highly conserved plasma
      tonicity control systems, uremic subjects demonstrate remarkable stability of
      their serum sodium. Dialysate is a synthetic interstitial fluid capable of
      reconstituting extracellular fluid composition through urea extraction and
      extremely efficient solute and solvent (salt and water) transfer to the patient.
      Subtle transdialyzer gradients deliver and remove large quantities of trace
      elements, solvent, and solute to patients, creating a variety of dialysis
      "disequilibrium" syndromes manifest as cellular and systemic distress. Every
      dialysis patient uses dialysate, and the most abundant chemicals in dialysate are
      salt and water. Despite its universal use, no consensus on dialysate composition
      or tonicity exists. This can only be explained if we believe that dialysate
      composition is best determined by matching unique dialysis delivery system
      characteristics to specific patient requirements. Such a paradigm treats
      dialysate as a drug and the dialysis system as a delivery device. Understanding
      the therapeutic and toxic profiles of this drug (dialysate) and its delivery
      device (the dialyzer) is important to safe, effective, goal-directed
      modifications of therapy. This article explores some of the historical rationale
      behind choosing specific dialysate tonicities.

PMID- 10936803
TI  - Sodium modeling.
AB  - The most serious side effects induced by hemodialysis therapy are caused by
      changes in sodium concentration and subsequent water shift between the
      intracellular and extracellular fluid compartment. Because of inadequate
      precision of proportioning, a certain sodium concentration and considerable error
      in the measurement of sodium concentration in dialysis fluid and plasma water, an
      error of up to 10 g in the diffusive exchange of sodium chloride remains in most
      dialysis sessions. Common side effects occur within this sodium balance error.
      Sodium modeling is a simplified mathematical method to describe quantitatively
      the fluid exchange in the body caused by changes in extracellular sodium
      concentration. It is based on fundamental physiologic properties of sodium and
      its permeability through the corresponding membranes. It also explains the
      different working mechanisms of sodium- and urea-related changes in osmolarity.
      Sodium modeling is a helpful tool for the illustration of the effects of changes
      in sodium concentration and ultrafiltration rate on sodium balance during one
      dialysis session. Sodium profiling is a method employed to avoid unwanted side
      effects of hemodialysis therapy by deliberately changing the sodium concentration
      in dialysis fluid during the course of a dialysis session. Clinical reports on
      practicing sodium profiling are unsatisfactory, involving only short trial
      periods in most cases. Most of the studies reported positive sodium balance with
      temporary decreases in intradialytic hypotension and less blood volume reduction,
      but with increases in thirst and body weight. To date, no validated studies with
      suitable control of sodium balance have been published that clearly demonstrate
      the long-term benefits of this mode of therapy compared with the use of constant
      dialysate sodium concentrations.

PMID- 10936804
TI  - Relevance of the conductivity kinetic model in the control of sodium pool.
AB  - Changes in the body sodium pool caused by dialytic treatment have very important
      clinical implications, mainly in terms of intradialytic cardiovascular
      instability and interdialytic hyperhydration and hypertension with long-term
      cardiac hypertrophy and dilation. A kinetic model could be helpful in order to
      define the dialysate sodium concentration needed to match intradialytic
      hydrosodium removal with interdialytic sodium and water intake, but
      unfortunately, none of the sodium kinetic models are suitable for routine
      clinical application. Two conductivity kinetic models (one for hemodialysis and
      one for paired filtration dialysis) have been developed on the basis of the
      linear relationship between the sodium content and conductivity of every saline
      solution and plasma water and according to basic theory for ionic dialysance
      determination. These models make it possible to know at the start of each session
      the dialysate conductivity needed to obtain the desired final plasma water
      conductivity or to know the latter when the former is known. Clinical evaluations
      showed that conductivity kinetic models are very precise and accurate and may be
      used instead of sodium kinetic models. Furthermore, they are suitable for routine
      use because they do not require blood sampling or laboratory determinations.
      Clinical application of the conductivity kinetic model has shown that the reduced
      variability of end-dialysis plasma water conductivity obtained when using the
      model to identify dialysate conductivity significantly reduces cardiovascular
      instability, even without any changes in average sodium removal. Given that ionic
      dialysance can be easily, inexpensively, and repeatedly measured at each dialysis
      session, it seems realistic to expect that conductivity kinetic modeling will
      soon become a part of everyday clinical practice.

PMID- 10936805
TI  - The link of biocompatibility to cytokine production.
AB  - Recent studies suggest that chronic inflammation plays a role in the pathogenesis
      of cardiovascular disease. Cytokines released from jeopardized tissues stimulate
      the liver to synthesize acute phase proteins, including C-reactive protein (CRP).
      Baseline levels of CRP in apparently healthy persons or in persons with unstable
      angina constitute an independent risk factor for cardiovascular events. More
      recently, it has been suggested that CRP is useful not only as a marker of the
      acute phase response, but is also involved in the pathogenesis of the disease.
      CRP may, in fact, directly interact with the atherosclerotic vessels or ischemic
      myocardium by activation of the complement system, thereby promoting inflammation
      and thrombosis. Several studies in uremic patients have implicated CRP as a
      marker of malnutrition, resistance to erythropoietin, and chronic stimulation in
      hemodialysis. An increased cytokine production secondary to blood interaction
      with bioincompatible dialysis components has been reported by several studies;
      interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and mainly IL-6
      are the three proinflammatory cytokines involved in the pathogenesis of
      hemodialysis-related disease. We have provided evidence for the occurrence of
      high CRP and IL-6 levels in chronic dialytic patients exposed to contaminate
      dialysate and suggest that backfiltration may induce a chronic, slowly developing
      inflammatory state that may be abrogated by avoiding backfiltration of
      contaminate dialysate. Therefore, CRP is implicated as a marker linking
      bioincompatibility associated with backfiltration and increased cytokine
      production with a clinical state of chronic inflammation.

PMID- 10936806
TI  - Clinical relevance of cytokine production in hemodialysis.
AB  - Blood-dialyzer interaction in hemodialysis has the potential to activate
      mononuclear cells leading to the production of inflammatory cytokines. The extent
      of activation is dependent on the dialyzer material used and is considered an
      index of biocompatibility. Cytokines, such as interleukin-1 beta (IL-1 beta),
      tumor necrosis factor-alpha (TNF-alpha), and IL-6, may induce an inflammatory
      state and are believed to play a significant role in dialysis-related morbidity.
      The interleukin hypothesis suggests that the release of proinflammatory cytokines
      acts as an underlying pathophysiologic event in hemodialysis-related acute
      manifestations, such as fever and hypotension. Nevertheless, a cytokine
      overproduction may alter sleep pattern in chronic hemodialyzed patients, thus
      explaining the presence of sleep disorders in these patients. A potential role of
      cytokines in chronic-related morbidity has also been suggested. High levels of
      some inflammatory cytokines are often associated with anemia caused by
      hyporesponsiveness to erythropoietin. Cytokine production may also play a
      relevant role in bone remodeling by regulating osteoblast/osteoclast cell
      functions and parathyroid hormone (PTH). Finally, cytokine release may have a
      long-term deleterious effect on mortality of uremic patients by altering immune
      response and increasing susceptibility to infections. Bioincompatibility of
      dialytic membranes may also contribute to malnutrition in dialysis patients by
      increasing the monocyte release of catabolic cytokines such as TNF-alpha and IL
      6. Bioincompatible dialytic treatment may induce an inappropriate monocyte
      activation and cytokine production, which, in turn, may mediate some of the
      immune and metabolic dysfunction associated with hemodialysis. The use of
      biocompatible dialytic membranes appears to reduce the monocyte activation and to
      improve the survival of hemodialysis patients.

PMID- 10936807
TI  - The quality of dialysate: an integrated approach.
AB  - The role of bacterial contamination of dialysis water with respect to chronic
      inflammatory diseases associated with long-term hemodialysis therapy has been
      greatly underestimated in the last two decades. In the present article, recent
      multicenter studies assessing the bacteriological quality of water and dialysate
      are discussed. In addition, we describe that pyrogenic substances of bacterial
      origin derived from contaminated dialysate penetrate intact dialyzer membranes
      with the consequence of the induction of an inflammatory response in the
      patients. The influence of dialyzer membrane characteristics on the passage of
      bacterial substances from dialysate into blood are discussed. Reaching the
      patients blood, bacteria-derived substances activate circulating mononuclear
      cells to produce proinflammatory cytokines. Cytokines such as interleukin-1 beta
      and tumor necrosis factor-alpha are mediators of the acute phase response
      resulting in elevated levels of acute phase proteins (for example, C-reactive
      protein). The consequence is a state of microinflammation that may contribute to
      progressive inflammatory diseases in chronic renal failure such as beta2
      microglobulin amyloidosis, protein catabolism, and atherosclerosis. The use of
      sterile dialysate reduces cytokine production and plasma levels of acute phase
      proteins, and may positively influence progressive inflammatory diseases in
      patients with end-stage renal failure.

PMID- 10936808
TI  - Relevance of oxidative and carbonyl stress to long-term uremic complications.
AB  - Oxidative stress is a disturbance of balance between oxidants and antioxidant
      species. The existence of an increased oxidative stress in chronic renal failure
      is supported by evidence of increased lipid, carbohydrate, and protein oxidation
      products in plasma and cell membrane. Recent studies have implicated the
      oxidative stress in the nonenzymatic biochemistry leading to irreversible protein
      modifications. Reactive oxygen species may directly alter proteins with the
      eventual formation of oxidized amino acids. Alternatively, reactive carbonyl
      compounds formed by the oxidation of carbohydrates and lipids may indirectly lead
      to advanced glycation or lipoxidation of proteins. Chronic uremia is associated
      with increased modification of protein caused by reactive carbonyl compounds
      derived from both carbohydrates and lipids. Increased carbonyl modification of
      proteins subsequently results in the rise of plasma and tissue contents of
      advanced glycation end products and advanced lipoxidation end products, in which
      the deleterious biological effects have been revealed. This article focuses on
      the irreversible nonenzymatic modification of proteins, which might, at least in
      part, contribute to the development of complications associated with chronic
      renal failure and long-term dialysis, such as atherosclerosis and dialysis
      related amyloidosis.

PMID- 10936809
TI  - Oxidant stress in hemodialysis: prevention and treatment strategies.
AB  - Oxidant stress has been implicated in a number of pathologies associated with
      uremia and hemodialysis. These patients have an increased incidence of
      cardiovascular disease, amyloidosis associated with protein modification, and
      notable changes in both function and structure of many cellular components.
      Oxidative reactions most frequently involving free radical intermediates play an
      important role in these processes and participate both directly and indirectly by
      further amplification of the inflammatory responses or in activation of signaling
      cascades mediating proliferation, differentiation, and cell death. Proteins and
      lipids are susceptible to oxidative degradation. These changes can ultimately
      alter important structural and functional characteristics and lead to
      pathological changes. This article addresses some of the diverse mechanisms and
      pathways involved in these changes, and suggests new therapeutic strategies in
      preventing oxidative damage.

PMID- 10936810
TI  - Nutritional aspects in hemodialysis.
AB  - The results of cross sectional studies throughout the world indicate that
      maintenance hemodialysis patients are at risk of malnutrition. Longitudinal
      studies show that malnutrition is associated with a reduced life expectancy
      mainly because of cardiovascular and infectious complications. Several factors
      are responsible for malnutrition of hemodialysis patients. Protein-energy intake
      is often reduced because of inappropriate dietary restrictions, anorexia, and
      taste alterations, promoting malnutrition in most patients entering dialysis.
      Intercurrent illnesses and frequent hospitalizations add to meal disturbances. A
      state of persistent catabolism may result from acidosis, resistance to anabolic
      factors such as growth hormone, insulin, and insulin-like growth factor-1, as
      well as a chronic inflammatory state caused by dialysis membrane and fluid
      bioincompatibility. In addition, losses of nutrients, including glucose, amino
      acids, proteins, and vitamins, occur during the dialysis treatment. Careful
      monitoring of dietary intakes is mandatory even in predialysis patients. In
      hemodialysis patients, the dose of dialysis should be adapted to correct acidosis
      and to relieve anorexia caused by accumulation of uremic toxins and
      hyperleptinemia. When malnutrition is established, active therapeutic
      interventions should take place, including intradialytic parenteral nutrition if
      oral supplementation has failed to improve nutritional status. Anabolism has been
      observed during the administration of recombinant growth hormone and insulin-like
      growth factor-1. Emerging therapeutic strategies against malnutrition may also
      involve a short period of daily dialysis.

PMID- 10936811
TI  - Pathophysiology of cardiovascular disease in hemodialysis patients.
AB  - Cardiovascular disease is the principal cause of morbidity and mortality in
      dialysis patients. The principal alterations responsible are left ventricular
      hypertrophy and arterial disease characterized by an enlargement and hypertrophy
      of arteries and the high prevalence of atheromatous plaques. Left ventricular
      hypertrophy is the consequence of combined effects of chronic hemodynamic
      overload and nonhemodynamic biochemical and neurohumoral factors characteristic
      of uremia. The hemodynamic overload is due to flow and pressure overload. The
      flow overload is tightly related to hyperkinetic circulation caused by anemia,
      arteriovenous fistula, or overhydration and is characterized by an enlargement of
      the left ventricular cavity. The pressure overload in these patients is more
      tightly related to abnormal geometry and function of large conduit arteries,
      principally the stiffening of arterial tree. The flow overload is also in large
      part responsible for remodeling of arterial tree, and as the heart and vessels
      are a coupled interactive physiological system, cardiac and vascular alterations
      occur in parallel, being induced to a great extent by the same hemodynamic
      abnormalities. The principal clinical consequences of left ventricular
      hypertrophy and arterial alterations are heart failure, ischemic heart disease,
      and peripheral artery disease. Cardiovascular alterations are only partly
      reversible, and efforts should be directed toward early prevention.

PMID- 10936812
TI  - Adsorption in sepsis.
AB  - The pathophysiology of sepsis offers a highly complicated scenario. In sepsis,
      endotoxin or other gram-positive-derived products induce a complex and dynamic
      cellular response, giving rise to several mediators known to be relevant in the
      pathogenesis of septic shock such as specific mediators, substances responsible
      for up- or down-regulation of cytokine receptors and cytokine antagonists,
      inactivators of translational or transductional pathways, and precursor
      molecules. In this review, we delve into some new concepts stemming up from the
      use of sorbents in continuous plasma filtration. Nonspecific simultaneous removal
      of several mediators of the inflammatory cascade have led to improved outcomes in
      animal models of septic shock and to improved hemodynamics in a pilot clinical
      study. It seems of great importance to explore all possible treatment techniques
      that may have a direct impact on circulating mediators of sepsis and that also
      may interfere with the imbalance between proinflammatory and anti-inflammatory
      substances in the critically ill patient with multiple organ failure. In this
      view, the application of sorbents appears to open new and interesting therapeutic
      options. The search for innovative treatments specifically targeted to the
      special needs of the critically ill patients seems therefore more important than
      the attempt to adjust concepts and technologies that are normally applied to
      patients with chronic renal failure.

PMID- 10936813
TI  - The final word.

PMID- 10936814
TI  - Optimal rotational interval for 3-dimensional echocardiography data acquisition
      for rapid and accurate measurement of left ventricular function.
AB  - BACKGROUND: Prolonged 3-dimensional echocardiography (3DE) acquisition time
      currently limits its routine use for calculating left ventricular volume (LVV)
      and ejection fraction (EF). Our goal was to reduce the acquisition time by
      defining the largest rotational acquisition interval that still allows 3DE
      reconstruction for accurate and reproducible LVV and EF calculation. METHODS:
      Twenty-one subjects underwent magnetic resonance imaging and precordial 3DE with
      2 degrees acquisition intervals. Images were processed to result in data sets
      containing images at 2 degrees, 4 degrees, 8 degrees, 16 degrees, 32 degrees, and
      64 degrees intervals by excluding images in between. With use of the paraplane
      feature, 8 equidistant short-axis slices were generated from each data set. The
      suitability of these short-axis slices for manual endocardial tracing was scored
      visually by 4 independent experienced observers. The LVV and EF were calculated
      by using Simpson's rule from 3DE data sets with 2 degrees, 8 degrees, and 16
      degrees intervals, and the results were compared with values obtained from
      magnetic resonance imaging. The probability of 3DE to detect LVV and EF
      differences was calculated. RESULTS: All patients were in sinus rhythm with a
      mean heart rate of 72 bpm (SD + or - 12). The LV short-axis images obtained with
      16 degrees rotational scanning intervals allowed LV endocardial tracing in all
      subjects. Good correlation, close limits of agreement, and nonsignificant
      differences were found between values of LVV and EF calculated with 3DE at 2
      degrees, 8 degrees, and 16 degrees rotational intervals and those obtained with
      magnetic resonance imaging. At steps of 16 degrees, 3DE had excellent correlation
      (r = 98, 99, and 99), close limits of agreement (+ or - 38, + or - 28.6, and + or
      - 4.8), and nonsignificant differences (P =.5,.8, and.2) with values obtained
      from magnetic resonance imaging for calculating end-diastolic LVV, end-systolic
      LVV, and EF, respectively. Three-dimensional echocardiography with use of 16
      degrees rotational intervals could detect 15-mL differences in end-diastolic
      volume with a probability of 95%, 11-mL differences in end-systolic volume with a
      probability of 92%, and 0.02 differences in EF with a probability of 95%.
      CONCLUSIONS: The 3DE data sets reconstructed with images selected at 16 degrees
      intervals from data sets obtained at 2 degrees precordial rotational acquisition
      intervals allowed the generation of LV short-axis images with adequate quality
      for endocardial border tracing. Therefore precordial acquisition at 16 degrees
      intervals would be sufficient for the reconstruction of 3DE data sets for LV
      function measurement. This would reduce the acquisition time while maintaining
      enough accuracy for clinical decision making and would thus make 3DE more
      practical as a routine method.

PMID- 10936815
TI  - Value of the Doppler index of myocardial performance in the early phase of acute
      myocardial infarction.
AB  - Prospective assessment of a nongeometric Doppler-derived index of combined
      systolic and diastolic myocardial performance was performed in 64 patients with
      acute myocardial infarction (MI) within 1 hour after their arrival to the
      hospital and in 39 age-matched healthy subjects. The index is defined as the sum
      of isovolumetric contraction time and relaxation time divided by ejection time,
      and is obtained by Doppler measurement from the mitral inflow and left
      ventricular outflow velocity-time intervals. The index was significantly higher
      in patients with MI compared with healthy subjects (P <.0001). In patients with
      MI and in-hospital congestive heart failure (CHF), the index was significantly
      higher compared with patients without CHF. In a multivariate regression analysis,
      the index >0.45 was the strongest independent predictor of the development of
      CHF. This simply obtained nongeometric Doppler index, assessed in the early phase
      of MI, detected and graded left ventricular dysfunction and identified patients
      at risk for the development of CHF.

PMID- 10936816
TI  - Use of peak systolic strain as an index of regional left ventricular function:
      comparison with tissue Doppler velocity during dobutamine stress and myocardial
      ischemia.
AB  - OBJECTIVES: The goals of this study were to examine peak systolic strain as an
      index of regional function in an animal model of inotropic stress and ischemia,
      and to compare these results with peak systolic myocardial tissue Doppler
      velocity (MDV). BACKGROUND: Myocardial tissue Doppler velocity is an objective
      measure of regional left ventricular responses to inotropic stimulation and
      ischemia, but it is affected by tethering from adjacent segments and
      translational movement. Myocardial Doppler strain (epsilon, relative change in
      length) is a more local measure of contractility, which can now be derived
      noninvasively from MDV. METHODS: Eight dogs underwent graded dobutamine infusion
      followed by coronary occlusion. Epicardial 2-dimensional echocardiography and
      color MDV of the left ventricle were obtained and digitized from the short-axis
      view at baseline and with dobutamine doses of 2, 4, and 8 microg/kg per minute.
      These were repeated 0, 10, 20, 45, and 90 seconds after occlusion of the left
      anterior descending artery (LAD) (n = 3) or circumflex coronary artery (n = 5).
      Dobutamine was continued at 8 microg/kg per minute during coronary occlusion. The
      peak systolic radial MDV (cm/s) and systolic strain (epsilon(s), percent
      thickening) in the anterior and posterior walls were measured off-line at each
      stage. RESULTS: Dobutamine caused an increase in MDV (P =.0001) and epsilon(s) (P
      =.09) above baseline values. Coronary occlusion caused a reduction in wall
      motion; after 45 seconds, all nonperfused segments were hypokinetic. There was a
      corresponding decrease in MDV and epsilon(s), but this occurred earlier for
      epsilon(s), and the difference between ischemic and nonischemic segments was
      greater for epsilon(s) than for MDV (P <. 03). Nonischemic regions trended to an
      increase in epsilon(s) (compensatory hyperkinesis), whereas MDV trended downward,
      probably reflecting the global decrease in left ventricular function. CONCLUSION:
      Both MDV and epsilon(s) increase with dobutamine and decrease during ischemia.
      epsilon(s) appears to respond to local ischemia earlier than MDV, perhaps because
      it is a more local measure. Thus epsilon(s) may prove to be an accurate parameter
      for the clinical recognition of regional ischemia.

PMID- 10936817
TI  - High-frame-rate tissue harmonic imaging enhances anatomic M-mode sections of the
      left ventricle in short-axis view.
AB  - BACKGROUND: High-frame-rate echocardiography (HFRE) and tissue harmonic imaging
      (THI) may improve image quality, thereby enabling anatomic M-mode sections of
      left ventricular (LV) wall segments to be visualized in various planes in the
      short-axis view. OBJECTIVES: The goals of this study were to compare image
      quality between HFRE and conventional-frame-rate echocardiography (CFRE) and
      between fundamental imaging (FI) and THI, and to obtain anatomic M-mode values of
      basal short-axis LV segments from healthy subjects for use in the evaluation of
      abnormal segments in patients with myocardial infarction (MI). METHODS AND
      RESULTS: The study included 28 healthy subjects and 15 patients with MI who
      underwent 2-dimensional echocardiography with an ultrasonographic system equipped
      with THI and anatomic M-mode. Left ventricular image cineloops at the basal short
      axis view that were obtained with 3 combinations of imaging techniques (FI +
      CFRE, FI + HFRE, and THI + HFRE) were digitized and displayed side-by-side in
      random order for comparison by blinded readers. M-mode sections were done in 3
      planes: anteroseptal-posterior, inferoseptal-lateral, and anterior-inferior basal
      segments. The THI + HFRE combination showed the best image quality with
      significant reduction in noise artifacts, resulting in a good signal-to-noise
      ratio and good tractability of all LV segments by anatomic M-mode. In healthy
      subjects, significant intersegmental differences existed in the diastolic and
      systolic thicknesses and in the percent systolic thickening of LV segments. In
      patients with MI, LV systolic thickening was significantly decreased in abnormal
      segments. No significant differences were noted in ejection fraction and
      fractional shortening among the 3 anatomic M-mode planes. CONCLUSION: High-frame
      rate tissue harmonic imaging improved image quality, thereby allowing
      reproducible anatomic M-mode measurements in various planes in the short-axis
      view and providing a convenient objective evaluation of global and regional LV
      function.

PMID- 10936818
TI  - Optimization of the size distribution and myocardial contrast effect of
      perfluorocarbon-filled albumin microbubbles by lyophilization under continuous
      negative pressure.
AB  - This study was undertaken to evaluate the effect of lyophilization under
      continuous negative pressure on perfluoropropane-filled albumin microbubble size
      distribution and myocardial contrast effect. Three different microbubble
      preparations were studied: (1) 1% albumin solution without a sugar (Optison), (2)
      1% albumin and 5% dextrose (PESDA), and (3) 1% albumin and 5% fructose (PESFA).
      The 2 preparations containing sugar were also subjected to lyophilization under
      continuous negative pressure. Microbubble size distribution was measured with a
      Coulter Multisizer II (Beckman Coulter, Inc, Fullerton, Calif). The microbubbles
      were injected intravenously into a rat during intravital microscopy of the
      mesenteric microcirculation. Finally, the different albumin microbubbles were
      injected intravenously into 10 dogs, and myocardial contrast effect was assessed
      by videodensitometry. Results of the Coulter counter studies showed lyophilized
      PESFA to have a smaller size distribution with 99.9% + or - 0.1% of microbubbles
      <10 microm in diameter and 88.5% + or - 1.4% <4 microm in diameter (P <.05
      compared with Optison or PESDA). On intravital microscopy, PESFA microbubbles
      behaved as intravascular tracers without microvascular plugging or coalescence.
      Finally, myocardial peak gray scale and area under the curve were significantly
      higher for PESFA than for PESDA or Optison, respectively. In conclusion,
      lyophilization of perfluoropropane-filled albumin microbubbles results in smaller
      microbubbles with a more uniform size distribution and brighter myocardial
      contrast. In addition, the substitution of fructose for dextrose improves size
      distribution and contrast effect. These findings have important implications
      regarding the use of novel imaging technologies that take advantage of
      microbubble destruction to image myocardial perfusion.

PMID- 10936819
TI  - Clinical utility of echocardiography in the management of implantable ventricular
      assist devices.
AB  - BACKGROUND: The high mortality rate of congestive cardiac failure, the cost and
      complications of cardiac transplantation, and the waiting list mortality rate
      resulting from donor organ scarcity have encouraged the development of surgical
      techniques as bridges to transplantation or as long-term palliative therapy.
      Implantable left ventricular assist devices are now routinely used as such a
      bridge, and within the REMATCH Trial, as permanent palliative devices in
      nontransplant candidates. These are mechanical managements with myriad mechanical
      complications and pitfalls. Echocardiography has been extensively used in our
      institution to detect and diagnose previously documented and hitherto
      unencountered complications of these procedures. METHODS AND RESULTS: The role of
      echocardiography in these procedures, including preoperative patient selection,
      intraoperative transesophageal echocardiography, and postoperative
      troubleshooting and late follow-up, is discussed. We describe our clinical
      echocardiographic approach, which has developed over 91 assist-device procedures.
      The relative frequency and clinical impact of specific anatomic, physiologic,
      hemodynamic, and mechanical features are described. New techniques such as the
      Doppler quantification of assist device inflow obstruction are illustrated, as
      are the device cannula position, the detection of device valve failure, and the
      parameters related to the remodeling procedure. CONCLUSIONS: Echocardiography in
      heart failure surgery has proved to be an invaluable tool in the diagnosis and
      management of mechanical complications. The experience gained in our institution
      may serve as an aid to new surgical programs treating these critically ill
      patients.

PMID- 10936820
TI  - Real-time transmission of full-motion echocardiography over a high-speed data
      network: impact of data rate and network quality of service.
AB  - With high-resolution network transmission required for telemedicine, education,
      and guided-image acquisition, the impact of errors and transmission rates on
      image quality needs evaluation. METHODS: We transmitted clinical echocardiograms
      from 2 National Aeronautics and Space Administration (NASA) research centers with
      the use of Motion Picture Expert Group-2 (MPEG-2) encoding and asynchronous
      transmission mode (ATM) network protocol over the NASA Research and Education
      Network. Data rates and network quality (cell losses [CLR], errors [CER], and
      delay variability [CVD]) were altered and image quality was judged. RESULTS: At
      speeds of 3 to 5 megabits per second (Mbps), digital images were superior to
      those on videotape; at 2 Mbps, images were equivalent. Increasing CLR caused
      occasional, brief pauses. Extreme CER and CDV increases still yielded high
      quality images. CONCLUSIONS: Real-time echocardiographic acquisition, guidance,
      and transmission is feasible with the use of MPEG-2 and ATM with broadcast
      quality seen above 3 Mbps, even with severe network quality degradation. These
      techniques can be applied to telemedicine and used for planned echocardiography
      aboard the International Space Station.

PMID- 10936821
TI  - Is the technically limited echocardiographic study an endangered species?
      endocardial border definition with native tissue harmonic imaging and Optison
      contrast: a review of 200 cases.
AB  - OBJECTIVE: Our goal was to determine whether contrast adds diagnostic value to
      both fundamental and native tissue harmonic imaging (NTHI) for endocardial border
      definition. METHODS: Two hundred consecutive patients who underwent stress
      echocardiography imaging were studied in either fundamental (n = 52) or NTHI mode
      (n = 148) with an Acuson Sequoia echocardiographic system. Contrast agent
      (Optison) was administered (0.5 to 1 mL) for enhancement of endocardial borders.
      Two- and 4-chamber views were analyzed before and after administration of
      contrast at peak stress for grading of 5 endocardial border segments. Scores from
      0 to 5 were assigned to each study for all the images both before and after
      contrast (0 = 0 segments completely visualized; 5 = 5 segments completely
      visualized). RESULTS: The use of Optison contrast significantly enhanced border
      definition when imaging was performed in either fundamental or NTHI mode.
      Addition of contrast resulted in better endocardial border definition in
      fundamental mode (4.1 + or - 1.0 versus 2.3 + or - 1.3, P <.001). However, in
      NTHI mode, the presence of contrast resulted in enhanced definition of
      endocardial border compared with its absence (4.8 + or - 0.5 versus 3.3 + or -
      1.1, P <.001). The combination of NTHI and contrast resulted in more
      visualization of endocardium when compared with the combination of fundamental
      imaging and contrast (4.8 + or - 0.5 versus 4.1 + or - 1.0, P <.001). In
      addition, interobserver agreement for border detection increased from 83% in
      fundamental mode without contrast to 95% with the use of NTHI with Optison (P
      <.001). CONCLUSION: As defined in 200 cases, the combination of NTHI with Optison
      contrast results in nearly complete and consistent endocardial border definition.

PMID- 10936822
TI  - Regional patterns of left ventricular systolic dysfunction after subarachnoid
      hemorrhage: evidence for neurally mediated cardiac injury.
AB  - Although left ventricular (LV) dysfunction has been described after subarachnoid
      hemorrhage (SAH), its pathophysiology, regional distribution, and reversibility
      remain uncertain. To test the hypothesis that regional wall motion patterns in
      SAH patients do not match the typical patterns observed in coronary artery
      disease, a segmental wall motion analysis was performed in 30 SAH patients with
      LV dysfunction. Both regional (n = 21) and global (n = 9) wall motion patterns
      were observed. Preservation of apical function relative to the base was observed
      in 17 (57%) of the 30 patients. Many of the wall motion patterns were atypical of
      coronary artery disease but correlated with the distribution of the myocardial
      sympathetic nerve terminals. Five subjects had follow-up echocardiograms with
      resolution of LV dysfunction in all cases. In conclusion, a previously
      unreported, apex-sparing pattern of LV dysfunction is described, providing
      indirect evidence for a neurally mediated mechanism of cardiac injury. Limited
      data indicate that LV dysfunction in SAH patients is potentially reversible.

PMID- 10936823
TI  - Superior vena caval syndrome: color flow Doppler detection of collateral venous
      channels.
AB  - Thrombosis of the superior vena cava (SVC) is an important clinical problem that
      requires prompt diagnosis. Confirmation of suspected SVC syndrome requires the
      use of an imaging study to document the obstruction and presence of collateral
      venous channels. Echocardiography is often used to evaluate suspected SVC
      obstruction; however, previous methods have allowed only indirect detection of
      collateral flow. We describe 3 patients with SVC obstruction in whom color flow
      Doppler allowed direct demonstration of collateral venous channels.

PMID- 10936824
TI  - Cardiac rupture during exercise stress echocardiography: a case report.
AB  - Stress echocardiography is widely used in the evaluation of coronary artery
      disease. Dobutamine stress echocardiography has been the preferred method, but
      many centers have adopted exercise stress echocardiography, which can visualize
      myocardial motion during physiologic stress testing. The complications of this
      method in the post-myocardial infarction period are the same as those identified
      in conventional exercise testing. We report a case of myocardial rupture in the
      postinfarction period during exercise stress echocardiography.

PMID- 10936825
TI  - Intracardiac echocardiography: newest technology.
AB  - Intracardiac echocardiography, defined as ultra-sonographic navigation and
      visualization within large blood-filled cavities or vessels of the cardio
      vascular system, has recently undergone refinement as a clinical tool through
      technologic advances in transducer miniaturization. Intra-cardiac ultra-sound
      catheters image at lower frequencies than current conventional intravascular
      ultrasound catheters used for intracoronary imaging. The lower imaging frequency
      enables greater tissue penetration, permitting whole-heart evaluation from a
      right-sided catheter position. Newer devices are steerable, have variable imaging
      frequency (5.5 to 10 MHz), and full Doppler capability (pulsed, continuous wave,
      and tissue Doppler). These advances have made intracardiac high-resolution
      imaging as well as hemodynamic assessment possible. A historical perspective,
      current capabilities and limitations, and potential clinical and research
      applications of this new imaging technique are discussed.

PMID- 10936826
TI  - Echocardiographic features of genetic diseases: part 8. Organ system.

PMID- 10936827
TI  - Be careful what you ask for-you may get it!

PMID- 10936828
TI  - Non-Hodgkin's lymphoma in a patient with ectrodactyly ectodermal dysplasia
      clefting syndrome.

PMID- 10936829
TI  - Maxillofacial injuries in the pediatric patient.
AB  - Approximately 22 million children are injured in the United States annually.
      Children are uniquely susceptible to craniofacial trauma because of their greater
      cranial-mass-to-body ratio. The pediatric population sustains 1% to 14.7% of all
      facial fractures. The majority of these injuries are encountered by boys (53.7% -
      80%) who are involved in motor vehicle accidents (up to 80.2%). The incidence of
      other systemic injury concomitant to facial trauma is significant (10.4% - 88%).
      The management of the pediatric patient with maxillofacial injury should take
      into consideration the differences in anatomy and physiology between children and
      adults, the presence of concomitant injury, the particular stage in growth and
      development (anatomic, physiologic, and psychologic), and the specific injuries
      and anatomic sites that the injuries affect. This comprehensive review, based on
      the last 25 years of the world's English-speaking surgical literature, presents
      current thoughts on the anatomic and physiologic differences between adults and
      children, a synopsis of childhood growth and development, and an overview of
      state-of-the-art management of the pediatric patient who has sustained
      maxillofacial injury.

PMID- 10936830
TI  - Expansile mandibular lesion in a child.

PMID- 10936831
TI  - A technique to manage gingival complications of third molar surgery.
AB  - Iatrogenic damage to the gingiva of the mandibular second molar is an often
      overlooked complication associated with surgery of impacted mandibular third
      molars. During impaction surgery, the peripheral gingival soft tissues may be
      damaged on flap elevation or destroyed during bone removal or tooth sectioning
      with rotary instruments. Loss of the often-thin band of keratinized gingiva of
      the second molar predisposes a patient to pain, plaque retention, inflammation,
      gingivitis, pocket formation, periodontitis, and alveolar bone loss. The
      surgically-induced bone defect associated with impaction removal exacerbates the
      aforementioned problems, which are difficult to treat with conventional
      techniques. This article attempts to address this issue and presents an new
      technique to manage such gingival complications.

PMID- 10936832
TI  - Upper lip length after V-Y versus continuous closure for Le Fort I level
      maxillary osteotomy.
AB  - PURPOSE: The purpose of this report is to document changes in lip length and
      thickness after Le Fort I maxillary osteotomy by using continuous versus V-Y
      closure. MATERIALS AND METHODS: This is a retrospective analysis of 18 patients
      who underwent Le Fort I maxillary osteotomy. Ten patients had a single midline V
      Y closure and 8 patients had simple continuous closure. Lateral cephalometric
      analysis was performed, and preoperative and 12-month postoperative changes in
      lip dimensions were calculated. Lip length and thickness were analyzed at 5
      points: A-point (A), subnasale (Sn), cervical margin of incisor (C), stomion
      superius (Ss) and labrale superius (Ls). The lengths from A to Sn, C to Ls, and
      Sn to Ss were calculated. RESULTS: After 12 months, there was no significant
      difference in lip length (P =.39) or thickness of the upper lip in its upper (P
      =.75) or lower (P =.19) parts, between the 2 groups. CONCLUSION: Lip length and
      width show no significant differences before surgery versus after surgery with
      either closure technique after Le Fort I osteotomy.

PMID- 10936833
TI  - Growth factor and cytokine gene expression in mechanically strained human
      osteoblast-like cells: implications for distraction osteogenesis.
AB  - OBJECTIVE: An understanding of bone cellular biology is a basic necessity to
      understanding events such as distraction osteogenesis. The goal of this study was
      to determine the effect of continuous cyclic mechanical stretch as a fundamental
      event in distraction osteogenesis on the expression of 3 bone growth factors,
      transforming growth factor-beta 1 (TGF-beta1), insulin-like growth factor 1 (IGF
      1), basic fibroblast growth factor (bFGF) and 2 cytokines, interleukin (IL)-1 (IL
      1) and 6 (IL-6) in human osteoblast-like cells. MATERIAL AND METHODS: A human
      osteoblast-like cell line, SaOS-2, capable of forming a ground substance and
      mineralizing it, was maintained. Cells were transferred to 6-well plates with
      flexible silicon bottoms grown to confluence and either subjected to tensile
      stretch for different time intervals or used as the control group. RNA was
      isolated to conduct Northern blot analysis for the expression of 3 bone growth
      factors, transforming TGF-beta1, IGF-1, bFGF, and 2 cytokines, IL-1 and IL-6.
      RESULTS: After 8 hours, mRNA for TGF-beta1 and IGF-1 increased in the
      experimental group, whereas bFGF decreased but cytokines IL-1 and IL-6 were not
      affected. At 16 hours, TGF-beta1, IGF-1, and bFGF showed increased levels of
      mRNA; IL-6 showed a slight increase. After 24 hours, TGF-beta1, IGF-1, bFGF, and
      IL-6 had increased mRNA levels. IL-1beta did never show significant alterations
      in mRNA production as compared with the control. CONCLUSION: Tensile stretch on
      osteoblast-like cells alter local regulation of bone formation, increasing the
      expression of bone growth factors, whereas catabolic cytokines are unaffected.
      These findings suggest a direct effect of mechanical strain on osteoblasts and
      may be the driving factors of bone growth during distraction.

PMID- 10936834
TI  - Effect of preservation of the inferior and posterior borders on recurrence of
      ameloblastomas of the mandible.
AB  - OBJECTIVE: The purpose of this study was to evaluate the experience and results
      of using a rational radical conservative approach in the surgical treatment of
      mandibular ameloblastomas. STUDY DESIGN: A retrospective analysis of every
      patient with an ameloblastoma of the mandible treated in the Department of Oral
      Medicine and Oral Surgery at the Jordan University of Science and Technology
      between 1989 and 1999 was conducted. All were operated on by the author, who used
      a uniform surgical protocol in every case. All soft tissues in contact or
      overlying the lesion and a wide margin of cancellous bone related to the tumor
      were destroyed. The compact bone comprising the lower border of the mandible and
      the posterior border of the ascending ramus together with the nutrient periosteum
      attached to them were preserved, thus maintaining the continuity of the mandible
      and the facial contours. When teeth, soft tissues, or both were involved, they
      were destroyed. All patients were reviewed annually for a follow-up period of 3
      to 10 years (mean, 6.5 years) by the same clinician. RESULTS: All ameloblastomas
      were located in the mandible; 21 were in the angle/molar region and the ascending
      ramus, and 2 cases were in the anterior region. There was no clinical or
      radiographic evidence of recurrence observed during the follow-up period.
      CONCLUSION: Ameloblastoma has a high rate of local recurrence if it is not
      adequately removed. The findings of this study to date suggest that the technique
      of rational radical conservative resection may have a place in the treatment of
      ameloblastoma of the mandible and is worthy of further trial.

PMID- 10936835
TI  - Direct oral microscopy and its value in diagnosing mucosal lesions: a pilot
      study.
AB  - OBJECTIVE: Clinical examination of the oral mucosa often leads to an uncertain
      diagnosis, and a supplementary biopsy with a histopathologic examination of the
      lesion is necessary to establish a definite diagnosis. However, the site for the
      biopsy is a subjective choice that sometimes raises doubts about its
      representativeness. So far, no simple and reliable method is available for
      selecting the most appropriate area for biopsy. STUDY DESIGN: In a prospective
      study, we performed direct oral microscopy (oral application of the colposcopy
      technique used in gynecology) in 35 patients with various clinical diagnoses,
      such as leukoplakia, oral lichenoid lesions, or suspected malignancy. First, the
      oral mucosa was examined with direct microscopy, and the most representative
      site, according to colposcopic criteria, was selected. Then, the mucosa was
      clinically inspected by an independent examiner. The best site for biopsy
      according to clinical criteria was noted, and any difference in biopsy sites was
      recorded. Biopsy specimens were taken from 2 of these sites. RESULTS: Twenty-nine
      patients (83%) showed changes in the vascular picture on microscopy, according to
      the colposcopy criteria. In 14 patients (40%), the biopsy sites identified by
      direct oral microscopy showed more advanced histologic signs than those selected
      by routine clinical examination (0.01 < P </=.05). Four patients (11%) had more
      advanced histologic signs in the biopsy samples, as identified during routine
      clinical examination. In 17 patients (49%), we found no differences between the
      biopsy specimens. CONCLUSION: Direct oral microscopy of mucosal lesions seems to
      offer advantages in selecting more representative sites for biopsy than routine
      clinical examination alone.

PMID- 10936836
TI  - Cardiovascular responses to epinephrine-containing local anesthetics for dental
      use: a comparison of hemodynamic responses to infiltration anesthesia and
      ergometer-stress testing.
AB  - OBJECTIVE: Cardiovascular effects of infiltration anesthesia have been documented
      in numerous studies. However, few studies have been carried out to compare the
      effects of infiltration anesthesia with the effects of exercise-stress testing.
      The purpose of this study was to examine this issue. STUDY DESIGN: Eight young
      and 13 older subjects were given infusions of epinephrine to produce
      cardiovascular responses comparable with those found in subjects undergoing
      infiltration anesthesia with 3.6 mL of lidocaine with 1:80,000 epinephrine (L-E).
      Cardiovascular responses to this drug treatment were evaluated with
      echocardiography and compared with those produced by ergometer exercise. RESULTS:
      The hemodynamic effects of L-E infiltration anesthesia were less than those
      produced by ergometer-stress testing at 25 watts (W) in young subjects and at 15
      W in the older subjects. The workload of this ergometer-stress testing was about
      4 metabolic equivalents (METS), which is approximately equivalent to the workload
      of walking 4.8 km/hr, doing light yard work (ie, raking leaves, weeding, or
      pushing a power mower), painting, or doing light carpentry. CONCLUSION: With the
      exception of some specific pathologic conditions, such as serious arrhythmia,
      infiltration anesthesia with 3.6 mL of L-E can be carried out safely on the
      patients who have exercise capacity of more than 4 METS.

PMID- 10936837
TI  - Sensitivity, specificity, and positive predictive value of oral opportunistic
      infections in adults with HIV/AIDS as markers of immune suppression and viral
      burden.
AB  - OBJECTIVES: The purpose of this study was to assess the use of human
      immunodeficiency virus (HIV)-related oral opportunistic infections as markers of
      immune suppression and viral burden in adults with HIV/acquired immunodeficiency
      syndrome (AIDS). METHODS: The population consisted of a single institution
      observational cohort involving 606 patients with HIV/AIDS with CD4 count data and
      277 with plasma viral load measurements examined between 1995 and 1999 for the
      presence of oral manifestations of HIV. Sensitivity, specificity, positive
      predictive value (PPV), and negative predictive value is reported for the
      association of specific oral lesions and lesion sets with CD4 counts <200
      cells/mm(3) and with plasma HIV RNA >/=20,000 copies/mL. RESULTS: Lesions with
      moderate-to-high PPVs for CD4 <200 cells/mm(3) were as follows: Kaposi's sarcoma
      (100%; P =.035), pseudomembranous candidiasis (82. 2%; P <.001), linear gingival
      erythema (70.0%; P =.015), hairy leukoplakia (66.3%; P <.001), angular cheilitis
      (60.0%; P =.128), and erythematous candidiasis (58.3%; P =.061). Necrotizing
      ulcerative periodontal diseases, HIV salivary gland disease, oral ulcers, and
      oral warts had PPVs below 50%. Concurrent infection with candidiasis and hairy
      leukoplakia had the highest PPV of 89.3%; P <. 001. PPVs for HIV RNA >/=20,000
      copies/mL ranged from 27.3% to 100%, with significant association only for
      pseudomembranous candidiasis. CONCLUSIONS: Specific common oral lesions are
      strongly associated with immune suppression, as measured by CD4 cell counts, and
      are modestly associated with high viral burden, thus serving as potential
      clinical markers of HIV viremia and the consequent destruction of the immune
      system with progressive HIV disease.

PMID- 10936838
TI  - Oral mucosal hyperpigmentation secondary to antimalarial drug therapy.
AB  - A case of oral mucosal hyperpigmentation resulting from antimalarial drug therapy
      is presented. The patient reported a history of long-term quinacrine therapy and
      exhibited diffuse blue-gray pigmentation of the nail beds and the skin of the
      nasal ala. Microscopic examination of the involved mucosa showed macrophages,
      containing both melanin and ferric iron, scattered within the connective tissue
      adjacent to the epithelium. The clinical, historical, and microscopic features of
      antimalarial-induced pigmentation are discussed. Other causes of diffuse or
      multifocal oral pigmentation are also addressed.

PMID- 10936839
TI  - Critical review of lymphomatoid papulosis of the oral cavity with case report.
AB  - A 60-year-old woman was referred to the Department of Dental Medicine at Long
      Island Jewish Medical Center for evaluation of multiple lesions of the tongue.
      She reported a long history of recurrent papular cutaneous eruptions that waxed
      and waned. A biopsy specimen of one of the cutaneous lesions was diagnosed as
      lymphomatoid papulosis. Sporadic, recurrent oral ulcers that resolved
      spontaneously were noted 10 to 14 days before the initial visit. These ulcers had
      recurred for the past 17 years. The most recent oral lesion was an erythematous,
      irregular, solitary ulcerated area on the middle third dorsum of tongue. The area
      quickly enlarged, ultimately developing extensive surface necrosis. Shortly
      after, a similar lesion on the posterior dorsum of the tongue developed. Biopsy
      specimens of the former lesion showed numerous, large, atypical, pleomorphic, and
      hyperchromatic cells with abundant mitoses. The large, atypical cells were
      immunohistochemically proven to be T lymphocytes. A diagnosis of lymphomatoid
      papulosis was made. Two weeks later, the tongue lesions had spontaneously and
      totally resolved. The clinical, histomorphologic, and immunohistochemical
      features, as well as gene rearrangement studies of this rare entity, are
      presented.

PMID- 10936840
TI  - Intraosseous salivary tissue: jawbone examples of choristomas, hamartomas,
      embryonic rests, and inflammatory entrapment: another histogenetic source for
      intraosseous adenocarcinoma.
AB  - PROBLEM: Hundreds of primary salivary neoplasms have been found to be completely
      enclosed within the marrow spaces of the maxilla and mandible, yet nonneoplastic
      salivary tissue has never been convincingly identified within marrow, either
      separately or adjacent to such neoplasms. This situation has forced the
      acceptance of an inherently awkward odontogenic origin for all intramedullary
      salivary carcinomas and adenomas. OBJECTIVE: The purpose of this study was to
      microscopically evaluate a large number of maxillofacial marrow samples for the
      presence of intramedullary salivary tissue. STUDY DESIGN: We microscopically
      reviewed 5034 maxillofacial bone samples from the Latvala Inflammatory Bone
      Registry for evidence of heterotopic salivary inclusions within the marrow
      tissues. Contributing surgeons were contacted for each identified case of
      intraosseous salivary tissue to assure that all submitted tissue was removed from
      within the marrow spaces rather than from overlying soft tissue. RESULTS:
      Thirteen of 5034 marrow samples (0.3%) contained heterotopic acinic hamartomas,
      salivary choristomas, embryonic salivary rests, or entrapped surface glands. Four
      additional hamartomas of the condyle are described. We report also the chance
      finding of incipient odontogenic epithelial neoplasms (n = 6) and odontogenic
      epithelial rests (n = 84) within the fatty marrow and outside the periodontal
      ligament spaces, confirming that not all odontogenic neoplasms are necessarily of
      periodontal ligament origin. CONCLUSION: The frequency rate for salivary
      choristomas, hamartomas, embryonic rests, and displaced surface glands within
      alveolar bone is no less than 2.6 of 1000 biopsied marrow samples. This provides
      an additional and quite logical histogenetic explanation for the presence of
      intraosseous salivary neoplasms.

PMID- 10936841
TI  - Expression of amelin and amelogenin in epithelial root sheath remnants of fully
      formed rat molars.
AB  - OBJECTIVE: To study the expression patterns of 2 enamel proteins, amelin and
      amelogenin, in the epithelial cells of the root sheath of fully formed rat
      molars. STUDY DESIGN: Twelve Sprague-Dawley rats, 50, 65, and 85 days of age,
      were used in this study. The maxillae of the rats were dissected free, and
      sagittal serial sections were made through the mesial root of the first molar. In
      situ hybridization of amelin and amelogenin mRNAs was performed, and
      immunohistochemical examinations of the corresponding proteins in the epithelial
      cells of the root sheaths of fully formed rat molars were performed. Antibodies
      against epidermal keratins were used to identify epithelial root sheath remnants.
      RESULTS: A group of epithelial cells, enclosed at the border between cellular
      cementum and dentin, expressed and synthesized amelin, but not amelogenin.
      Another group of epithelial cells, forming islands or strands, which were
      partially or totally incorporated in the matrix of the cellular cementum,
      expressed and synthesized both amelogenin and amelin. A third group of epithelial
      cells at the periphery of the cellular cementum expressed neither of the 2
      proteins. Epithelial cells at the surface of acellular cementum did not express
      either of the 2 proteins. CONCLUSION: This study showed that the epithelial root
      sheath remnants in rat molars express and synthesize amelogenin, as well as
      amelin. However, there are marked regional differences. The roles of the enamel
      proteins in the formation of the radicular hard tissues of the rat molars and in
      the maintenance of the periodontal tissues remain to be clarified.

PMID- 10936842
TI  - Pattern of bone resorption in vertically fractured, endodontically treated teeth.
AB  - PURPOSE: To evaluate the clinical pattern of alveolar bone resorption associated
      with vertically fractured, endodontically treated teeth in correlation to
      clinical symptoms. MATERIAL AND METHODS: The pattern of bone resorption was
      evaluated in 66 maxillary premolars, 13 mandibular premolars, and 31 mesial roots
      of mandibular molars extracted during an 18-month period because of vertical root
      fractures. Type and duration of symptoms were recorded and correlated to the
      pattern of bone resorption. RESULTS: A V-shaped pattern osseous defect
      (dehiscence) was typical (91%) to the buccal plate rather than a U-shaped
      shallow, rounded, slow grade resorption in the palatal or lingual plate.
      Fenestration of the buccal plate was observed in 10 patients (9%). A positive
      correlation between type of symptoms and amount of buccal bone resorption was
      found (P <.0001). The resorptive defect was always facing the fracture line.
      CONCLUSIONS: A typical pattern of bone resorption in vertical root fracture cases
      as shown in this study can be helpful to the clinician in diagnosing vertical
      root fracture when an exploratory full flap surgical procedure is performed.

PMID- 10936843
TI  - The role of quantitative single photon emission computerized tomography (SPECT)
      in the osseous integration process of dental implants.
AB  - OBJECTIVE: To evaluate the integration process of endosseous dental implants by
      using quantitative bone single photon emission computerized tomography (SPECT).
      METHODS: Five consecutive patients receiving titanium implants (Astra Tech,
      Molndal, Sweden) in the normal edentulous jaw were evaluated by bone SPECT before
      loading and at regular intervals up to 5 months after loading. Osteoblastic
      activity at the implant site was compared with activity within the skull
      (reference) to calculate an osteoblastic activity index (AI). RESULTS: A time
      activity curve obtained by plotting AI against time over 5 months showed 3
      distinct phases of osteoblastic activity: (1) a rise in osteoblastic activity,
      part of which may reflect postoperative changes, (2) maximum activity about 1
      month after implant, and (3) a gradual falloff in the AI, which returned to pre
      implant levels at about 4 months. CONCLUSIONS: We conclude that this method
      offers a simple, reproducible, objective, and physiologic approach to studying
      the osseous integration process that occurs after endosseous dental implants. In
      this small series of patients, this osseous integrative process appears to have
      become established approximately 4 months after loading. This method also has the
      capability of quantitating bone activity in absolute terms of microCi/gram
      (microcuries per gram) and can be useful when bone grafting and other surgical
      procedures are involved.

PMID- 10936844
TI  - Influence of developer exhaustion on accuracy of quantitative digital subtraction
      radiography: an in vitro study.
AB  - OBJECTIVE: The aim of the study was to evaluate the influence of developer
      exhaustion on accuracy of quantitative digital subtraction radiography. STUDY
      DESIGN: Six objects, each incorporating a section of dry human mandible, were
      radiographed with 4 exposure times. Baseline films were processed in fresh
      solutions, whereas follow-up films were processed in fresh and in increasingly
      exhausted solutions (ie, 1, 2, and 3 weeks old). Bone loss and bone gain were
      computer simulated in 17 regions of interest on baseline radiographs. Area and
      volume of changes in mineralization were measured in subtracted images, obtained
      by subtraction of baseline from their corresponding follow-up radiographs.
      Friedman's 2-way analysis of variance by ranks and Wilcoxon signed-rank test were
      used for statistical analysis. RESULTS: Because of exhausted developer, bone loss
      was relatively underestimated from 6.6% to 16.5% (P <.05), whereas bone gain was
      relatively overestimated from 9.7% to 16.7% (P <.05). CONCLUSIONS: This in vitro
      study demonstrates that films for quantitative digital subtraction radiography
      should be processed in fresh developer or error might be introduced.

PMID- 10936845
TI  - Magnetic resonance imaging-based joint space measurements in temporomandibular
      joints with disk displacements and in controls.
AB  - OBJECTIVE: Previous studies have discussed a posterior displacement of the
      condyle as a possible risk factor for the development of disk displacements (DDs)
      of the temporomandibular joint (TMJ). The objective of this study was to compare
      the posterior and anterior joint spaces in healthy TMJs with those of patients
      who present different forms of DDs. STUDY DESIGN: The anterior and posterior
      joint spaces from 58 patients with unilateral or bilateral DD with reduction
      (DDR) or without reduction (DDNR) and from 30 healthy volunteers were measured
      with 3 sagittal magnetic resonance images (MRIs) from each TMJ in the maximum
      intercuspid position. RESULTS: Measurements of anterior and posterior joint
      spaces showed a good interexaminer reproducibility (rank correlation coefficients
      ranging from 0.88 to 0.95). Patients with bilateral DDR demonstrated a
      significantly more posterior position of the condyle, as compared with controls
      and patients with bilateral DDNR. DDNR presented a significant reduction of the
      anterior and the posterior joint spaces, leading to a mean concentric position of
      the condyle. Patients with unilateral DDR or DDNR demonstrated a greater
      variability of anterior and posterior joint spaces, compared with patients with a
      bilaterally identical type of DD. CONCLUSIONS: The data of this MRI-based
      clinical study indicate that different stages of disk displacements are
      associated with significant changes of condylar position. The variation of
      anterior and posterior joint spaces was influenced by the diagnosis of the
      contralateral joint.

PMID- 10936846
TI  - In vivo, thyroid and lens surface exposure with spiral and conventional computed
      tomography in dental implant radiography.
AB  - OBJECTIVE: To compare the surface dose exposure to the lens of the eye and the
      thyroid gland received by patients undergoing spiral and conventional computed
      tomography (CT) examinations during dental implant pretreatment evaluation in
      critical radiosensitive structures of the maxillofacial region. STUDY DESIGN: Two
      groups of 10 patients each had a dental implant CT examination performed, with 5
      patients in each group having maxillary and 5 having mandibular examinations. One
      group was examined with conventional CT and the other with spiral CT. Seven
      examination parameters were standardized to both types of examinations. Lithium
      fluoride thermoluminescent dosimeters were placed over the thyroid gland, lateral
      orbit, and infraorbital foramen of each patient to measure the surface dose. The
      Wilcoxon rank sum test was used to compare doses, with statistical significance
      set at P <.05. RESULTS: For the maxillary examination, there was a 57.4%
      reduction in the surface dose at the lateral orbit, 47% at the infraorbital
      foramen, and 60.8% at the thyroid when spiral CT was used instead of conventional
      CT with the same parameters. Similarly, for the mandibular examination, there was
      a 57.4% reduction at the lateral orbit, 60% reduction at the infraorbital
      foramen, and 70.9% at the thyroid. All the dose reductions were statistically
      significant at P <.05. CONCLUSION: The use of spiral CT for preimplant evaluation
      reduces the surface absorbed dose in certain critical structures of the
      maxillofacial region compared with conventional CT.

PMID- 10936856
TI  - Vitamin E reduces platelet adhesion to human endothelial cells in vitro.
AB  - Although it has been reported that vitamin E (alpha-tocopherol) can reduce
      platelet adhesiveness and aggregation in vivo, the mechanism is still unknown.
      Therefore, the aim of the present study was to determine whether incubations of
      platelet-rich plasma (PRP) with vitamin E influence platelet adhesion to cultured
      endothelial cells. To exclude blood plasma involvement, also washed platelets
      were pretreated with alpha-tocopherol. Vitamin E (0.5-1.0 mM) was added to PRP or
      washed platelets. Endothelial cells in monolayer were incubated with thrombin
      activated platelets (1 or 2 U/ml). After 1 hr of incubation, non-adhered
      platelets were removed and counted. Treating of PRP with alpha-tocopherol
      inhibited platelet adhesion to endothelial cell monolayer. This effect was dose
      dependent on concentrations of alpha-tocopherol and thrombin. In our experiments
      PRP was treated with alpha-tocopherol and endothelial cell monolayer was used as
      test surface. These findings agree with previous observations on the adhesivity
      of platelets to synthetic surfaces after dietary vitamin E in healthy volunteers.
      When washed platelets were incubated with alpha-tocopherol, no significant
      reduction of adhesion was detectable. As preincubation of washed platelets with
      alpha-tocopherol does not inhibit platelet adhesion, it may be supposed that the
      effect of vitamin E does not occur in a directly cellular mechanism. The data
      suggest that alpha-tocopherol may reduce platelet adhesiveness probably after
      incorporation by plasma lipoproteins.

PMID- 10936857
TI  - Diagnosis and characterization of acute erythroleukemia subsets by determining
      the percentages of myeloblasts and proerythroblasts in 69 cases.
AB  - Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase
      in red cell precursors and myeloblasts. Three subsets have been described: M6A
      (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia);
      and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was
      undertaken to define and compare the clinical courses and survival outcomes among
      M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia
      were categorized as consisting of >/=50% erythroid of all nucleated cells and M6A
      with >/=30% myeloblasts/nonerythroid component; M6B with >/=30%
      proerythroblasts/erythroid component; and M6C with >/=30% myeloblasts and >/=30%
      proerythroblasts. The demographics, cell type distribution, and survival (mean +/
      sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C
      patients. No significant difference was seen among the groups in age, sex, or
      treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants
      showed a statistically significant increase in the percentage of bone marrow
      erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios.
      Comparing the groups for survival, M6B (3 +/- 3.6 months) versus M6A (25 +/- 28
      months), P< 0. 002, and M6C (10 +/- 13 months) versus M6A, P< 0.01 had a poorer
      prognosis. Calculating the proerythroblasts as a component of total bone marrow
      erythroids provides a complimentary method for delineating the pure red cell
      erythroleukemia (M6B) and mixed variant (M6C), similar to that for the
      myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate
      erythroleukemia subtypes, innovative treatments are indicated to target the
      malignant erythroid population, which is resistant to myeloid-based therapies.

PMID- 10936858
TI  - A (GATA)(7) motif located in the 5' boundary area of the human beta-globin locus
      control region exhibits silencer activity in erythroid cells.
AB  - A 40-bp DNA, consisting of seven tandem GATA repeats, is located near the HS5
      site in the 5' boundary area of the locus control region (LCR) of human beta
      globin gene. This (GATA)(7) motif, named 5a, exhibits silencer activity in
      erythroid cells. In transfected, recombinant plasmids containing the
      chloramphenicol acetyltransferase (CAT) reporter gene, 5a repressed the activity
      of the cis-linked housekeeping phosphoglycerate kinase (pgk) promoter; 5a also
      repressed the activity of the cis-linked HS2 enhancer regardless of whether the
      CAT gene was driven by the pgk or the epsilon-globin promoter. Repression by 5a
      was most severe when 5a was spliced upstream of HS2 at a distance of less than
      200 bases from the HS2 enhancer core. The silencer activity of 5a was independent
      of whether the component GATA motifs were in head to tail orientation as in the
      wild type 5a or in head to head or tail to tail orientation as in a mutant 5a.
      Band shift experiments show that the GATA-1 protein binds to both 5a and the
      mutant 5a and forms a large protein complex. Together, the results suggest that
      GATA-1 bound at 5a is a strong, proximal repressor of HS2 enhancer activity.

PMID- 10936859
TI  - Pneumococcal vaccine administration associated with splenectomy: the need for
      improved education, documentation, and the use of a practical checklist.
AB  - An audit was performed of the documentation of pneumococcal vaccination in
      splenectomy patients in three major hospitals involving a geographical population
      base of 350,000 patients in British Columbia, Canada. Overall, 111 of the 164
      hospitalized splenectomy patients (68%) had received pneumococcal vaccination. Of
      elective splenectomy cases, only 11 of 55 (20%) had been vaccinated prior to
      surgery, as is currently recommended. One hundred fifty-five patients (95%) had
      splenectomy status mentioned in the discharge summary. However, only 35 (21%) had
      mention of vaccination status, 10 (6%) mention of the need for future
      revaccination, and only 8 (5%) notation of the possibility of future infectious
      risks. The rate of pneumococcal vaccination was as satisfactory as any reported
      in the literature to date. However, there is need for improved education in
      relation to the timing of vaccination and discharge summary documentation. A
      checklist for potential splenectomy patients may aid in improving this situation
      as may geographically based splenectomy registries.

PMID- 10936860
TI  - Coagulation factor XI is a contaminant in intravenous immunoglobulin
      preparations.
AB  - A small number of thromboembolic events, including deep venous thrombosis and
      myocardial infarction, have been reported in patients receiving IVIG. These
      events have primarily occurred in patients receiving high-dose IVIG and have been
      attributed to an increase in blood viscosity. To test the hypothesis that a
      procoagulant might be present in IgG preparations, twenty-nine samples of
      intravenous immunoglobulin (IVIG) from eight different manufacturers were assayed
      for procoagulant activity. Twenty-six of these samples shortened the clotting
      time of factor XI-deficient plasma. Of these, fourteen samples had factor XI
      activities greater than 0.001 U/ml of normal pooled plasma. The remaining samples
      possessed less than 0. 001 U/ml of normal plasma activity. The procoagulant
      activity in these samples could be inhibited by an anti-factor XI polyclonal
      antibody, suggesting that the procoagulant activity was factor XI. The
      procoagulant activity increased in two samples after storage at 4 degrees C for 4
      weeks, likely as a result of factor XIa autoactivation. Additionally, activity in
      some IVIG samples was able to directly activate factor IX, indicating that
      activated factor XI was present in these samples. Finally, the degree of factor
      XI(a) contamination in the samples was correlated with the manufacturer,
      suggesting that variations in the manufacturing process or source plasma affect
      the level of factor XI in the IVIG product. Because addition of small amounts of
      factor XIa to plasma can lead to production of significant amounts of thrombin,
      we suggest that factor XIa present in some IVIG preparations could contribute to
      the in vivo risk of thrombosis after IVIG therapy.

PMID- 10936861
TI  - Plasma levels of activated protein C-protein C inhibitor complex in patients with
      hypercoagulable states.
AB  - Plasma levels of activated protein C (APC)-protein C inhibitor (PCI) were
      significantly increased in patients with disseminated intravascular coagulation
      (DIC), thrombotic thrombocytopenic purpura (TTP), acute myocardial infarction
      (AMI), pulmonary embolism (PE), or deep vein thrombosis (DVT) and in patients
      undergoing hemodialysis (HD). Plasma levels of APC-alpha(1)-antitrypsin (AT)
      complex were significantly increased in patients with DIC and in those with TTP.
      Plasma levels of PCI were significantly decreased in patients with DIC, non-DIC,
      or TTP and in those undergoing HD. In the pre-DIC stage, the plasma levels of APC
      PCI complex were significantly increased but not those of APC-alpha(1)-AT
      complex. These data suggest that measurements of APC-PCI complex and APC-alpha(1)
      AT complex may be useful for the diagnosis of DIC. After treatment of DIC, the
      plasma levels of APC-PCI complex and APC-alpha(1)-AT complex were significantly
      decreased, but not those of PCI. Plasma levels of thrombin-antithrombin complex
      (TAT), plasmin-alpha(2)-plasmin complex (PPIC), D-dimer, and soluble fibrin
      monomer (SFM) were markedly increased in patients with DIC or pre-DIC and were
      moderately increased in patients with non-DIC, TTP, AMI, PE, or DVT and in those
      undergoing HD. The receiving operating characteristic (ROC) analysis showed that
      SFM and the APC-PCT complex are useful markers for diagnosis of DIC. The
      specificity of plasma TAT and PPIC levels was low. The positive rate of APC-PCI
      complex was higher than 90% with DIC, TTP, AMI, PE, and it was higher than 60%
      with DVT and HD. Since the APC-PCI complex was elevated not only in patients with
      venous thrombosis but also in those with arterial thrombosis, components of the
      protein C pathway might be useful markers for the diagnosis of arterial
      thrombosis.

PMID- 10936862
TI  - High rate of TTV infection in multitransfused patients with pediatric malignancy
      and hematological disorders.
AB  - The prevalence of transfusion-transmitted virus (TTV) infection has not been
      known in patients suffering from pediatric malignancies and hematological
      disorders who receive blood transfusion and/or blood products during treatment.
      Blood samples were taken from 75 patients. TTV infection was identified when TTV
      DNA was detected in serum by a polymerase chain reaction (PCR) assay. Hepatitis C
      virus (HCV) and hepatitis G virus (HGV) RNA were also assayed by PCR. TTV DNA was
      detected in 38 of 75 patients (51%). In 4 of 38 patients, the amount of blood
      transfused was less than 3 units. By time since last transfusion, TTV DNA was
      detected in 12 of 35 patients after more than 4 years, 12 of 21 between 1 and 4
      years, and 14 of 19 within 1 year. Six patients had mixed infection of TTV and
      HCV, and 12 patients had mixed infection of TTV and HGV. Three different kinds of
      virus were found simultaneously in serum from 3 patients. Eight out of 75
      patients showed abnormal levels of alanine aminotransferase (ALT) (>40 IU/liter),
      and 3 of them had TTV DNA. All patients who had TTV DNA and elevated ALT levels
      also were positive for HCV RNA and HGV RNA. The prevalence of TTV infection is
      high in patients with pediatric malignancies and hematological disorders after
      episodes of blood transfusion. Transfusion is one of the most important risk
      factors for TTV infection regardless of the amount of blood transfused.

PMID- 10936863
TI  - The prevalence of factor V R506Q mutation-Leiden among apparently healthy
      Lebanese.
AB  - Resistance to activated protein C (APC) degradation caused by a specific point
      mutation in the factor V (FV) gene, FV:R506Q or FV-Leiden, which replaces Arg506
      with Gln at the APC cleavage site within the FV gene, is the most prevalent
      inherited caused of venous thrombosis. Recent reports suggested that the
      prevalence of FV-Leiden is high among Caucasians, and very low among non
      Caucasians, thereby suggesting that FV-Leiden has originated as a single event in
      a primary focus. Insofar as FV-Leiden is associated with increased risk of
      thromboembolic diseases, coupled with its selective worldwide distribution, the
      aim of this study was to determine the prevalence of FV-Leiden in Lebanon and
      compare it with those of other countries of Caucasian and non-Caucasian origin.
      FV-Leiden was determined by PCR, followed by hybridization with specific wild
      type and mutant DNA probes. By screening 174 healthy Lebanese subjects, 25 were
      shown to carry the FV-Leiden mutation, giving an allele frequency of 7.4% and an
      overall prevalence rate of 14.4%. Of the 25 FV-Leiden carriers, 24 were in the
      heterozygous state while one was in the homozygous states. No statistical
      difference in the FV-Leiden prevalence was noted with respect to age, gender, or
      sect. In addition to Lebanon, which had the highest prevalence rate reported thus
      far (14.4%), a high prevalence of FV-Leiden was reported for Syria (13.6%),
      Greece-Cyprus (13.4%), and Jordan (12.3%), an indication that the Eastern
      Mediterranean is the primary focus of FV-Leiden mutation. The high prevalence of
      FV-Leiden in Lebanon suggests that screening for this mutation must be considered
      for those with a family history, and/or those with additional risk factors for
      venous thrombosis.

PMID- 10936864
TI  - Thrombotic thrombocytopenic purpura in pulmonary-renal syndromes.
AB  - Thrombotic thrombocytopenic purpura pathologically consists of a thrombotic
      microangiopathy that classically spares lung tissues. We describe a case of TTP
      that presented as a pulmonary-renal syndrome. In reviewing the international
      literature, pulmonary involvement is not as rare as once was thought, and the
      diagnosis of TTP should be considered in the differential diagnosis of pulmonary
      renal syndromes.

PMID- 10936865
TI  - Splenosis presenting as occult gastrointestinal bleeding.
AB  - A 48-year-old man presented with recurrent gastrointestinal bleeding and anemia.
      Routine endoscopic evaluation was nondiagnostic. Angiography demonstrated
      multiple apparent arteriovenous malformations. Exploratory laparotomy revealed
      numerous splenic implants along the small and large bowels, some of which had
      apparently eroded through the bowel mucosa and bled. Excision of these
      penetrating lesions prevented further bleeding. An incidentally noted renal cell
      cancer was also resected. The patient's splenosis was the result of childhood
      trauma that caused splenic rupture and precipitated splenectomy. Splenosis
      develops frequently following traumatic splenic rupture. Experimental evidence
      suggests that the presence of an intact spleen suppresses the growth and
      development of splenic implants. Following splenectomy, splenules may replace
      some of the "housekeeping" and immunologic functions of the spleen, but even
      patients with documented splenosis should be considered functionally hyposplenic.
      While in most cases splenules cause no symptoms, splenosis must be considered in
      the differential diagnosis of previously splenectomized patients who present with
      unexplained masses or occult bleeding.

PMID- 10936866
TI  - Down's syndrome with myelodysplastic syndrome showing t(7;11)(p13;p14).
AB  - We report a boy with Down's syndrome (DS) who developed myelodysplastic syndrome
      (MDS) after spontaneous remission of transient myeloproliferative disorder (TMD)
      at birth. Chromosomal analysis of the blasts in the MDS phase demonstrated
      t(7;11)(p13;p14) which had not been detected in the TMD phase. NUP98-HOXA9
      chimera mRNA, which is known to be involved in t(7;11)(p15;p15) translocation in
      acute myeloid leukemia (AML), was not detected by reverse transcriptase
      polymerase chain reaction, and NUP98 rearrangement was not detected by Southern
      blot analysis of the blasts in the MDS phase. Reciprocal translocation is very
      rare in AML/MDS in DS, and the t(7;11)(p13;p14) found in our patient was
      different from the recurrent translocation t(7;11)(p15;p15) previously reported.

PMID- 10936867
TI  - A case of monoclonal gammopathy associated with acute myelomonocytic leukemia
      with eosinophilia suggested to be the result of lineage infidelity.
AB  - Acute myelomonocytic leukemia (AMMoL) accompanied by monoclonal gammopathy is a
      rare condition, and its pathogenesis and the cytogenetic mechanism of such
      leukemogenesis have not been determined in detail. A case of AMMoL with
      eosinophilia accompanied by immunoglobulin G kappa monoclonal gammopathy is
      described. Immunophenotypic studies of the peripheral blood and bone marrow
      mononuclear cells revealed no evidence of abnormally proliferating cells of B
      lineage. DNA analyses of bone marrow mononuclear cells containing leukemic cells
      revealed rearrangement of the kappa-light chain (Igkappa) gene and c-myc and c
      jun proto-oncogenes. The intensities of the rearranged bands for these genes on
      Southern blot analysis suggested the existence of a major population of leukemic
      cells with rearranged Igkappa gene and minor population(s) of leukemic cells with
      rearranged c-myc and/or c-jun proto-oncogene(s) in the patient's bone marrow and
      indicated the occurrence of genetic evolutionary changes in leukemic cells in
      this patient before starting chemotherapy. These results suggest that these
      leukemic cells are the most likely candidate for immunoglobulin G kappa
      monoclonal protein production, and structural abnormalities of c-myc and c-jun
      proto-oncogenes may have contributed to the evolution of leukemic cells in this
      patient.

PMID- 10936868
TI  - A de novo philadelphia chromosome-positive acute mixed-lineage leukemia with both
      major and minor BCR/ABL mRNA transcripts.
AB  - A patient with a Philadelphia chromosome (Ph)-positive acute mixed-lineage
      leukemia (AMLL) expressing both major and minor BCR/ABL mRNA transcripts is
      described. Phenotypic analysis of the leukemic blasts revealed positivity for
      both myeloid and B-cell lineages. Southern blot analysis showed a rearrangement
      of the immunoglobulin heavy chain (IgH) gene. Reverse transcriptase polymerase
      chain reaction (RT-PCR) analysis showed the expression of both major and minor
      BCR/ABL mRNA transcripts. To our knowledge, this is the first report of AMLL
      expressing both major and minor BCR/ABL mRNA transcripts and rearrangement of the
      IgH gene.

PMID- 10936869
TI  - Successful allogeneic stem-cell transplantation with prophylactic stepwise G-CSF
      primed-DLIs for relapse after autologous transplantation in mantle cell lymphoma:
      a case report and literature review on the evidence of GVL effects in MCL.
AB  - Mantle cell lymphoma (MCL) is a distinctive clinicopathologic entity and
      represents 2-8% of all non-Hodgkin's lymphomas. The median survival of patients
      with MCL is only 3 years, and none of the available conventional chemotherapy
      regimens appears curative. Encouraging results have been reported with high-dose
      chemotherapy with autologous stem-cell transplantation (autoSCT). However, a
      plateau in disease-free survival was not observed in relapsed MCL on the autoSCT
      trials. Promisingly, alloSCT appears to induce durable remissions via a graft
      versus-lymphoma (GVL) effect. Donor lymphocyte infusions (DLIs), by virtue of a
      GVL effect, have been shown to induce durable remissions in a few cases with
      refractory MCL that recur after alloSCT. In this article, we review the
      literature on the evidence of the GVL effects in MCL and describe a patient with
      relapsed MCL shortly after high-dose chemotherapy with autoSCT. The patient was
      then successfully treated with Bu/Cy/VP-16 for an alloSCT followed by DLIs in a
      stepwise fashion. MNCs > 10 x 10(8)/kg were collected by two large-volume
      leukaphereses from the donor. Harvested stem cells from the 2(nd) day were
      cryopreserved for the future use as prophylactic DLIs to be given in a stepwise
      fashion. Cyclosporin and methotrexate were used for GVHD prophylaxis. He had
      achieved only a partial response by D+64 post transplant. G-CSF-primed
      cryopreserved DLIs were then infused on D+64 and D+92 to enhance the GVL effect.
      Grade 3 intestinal GVHD developed 20 days after the 2(nd) DLI and was partially
      controlled with the combination of cyclosporin, prednisone, and mycophenolate
      mofetil. Clinical complete remission was observed at D+112, and maintained until
      the last follow-up day (D+615). Our findings suggest that alloSCT followed by
      prophylactic DLIs may offer a curative approach to refractory MCL.

PMID- 10936870
TI  - Gentle yet effective treatment for elderly patients with refractory or relapsing
      multiple myeloma.
AB  - Fourteen patients, aged 65-85 years, with refractory (11) or relapsing (3)
      multiple myeloma were treated with a "protracted-sequential" protocol comprising
      vincristine 1-2 mg or vindesine 3 mg/M(2) (max. 5 mg) IVI over 4 hr on D1,
      prednisolone 40-50 mg PO D1-14, and melphalan 2-4 mg PO or cyclophosphamide 50
      100 mg PO D15-28; cycles were repeated at 4-6 weekly intervals. Treatment was
      continued for 12 months if the response was optimal or indefinitely if the
      response was suboptimal. Five patients responded optimally; their survival from
      the commencement of this protocol ranged from 30 to 120 months. The other nine
      patients achieved a partial response, their survival ranging from 4+ to 79
      months. The treatment is simple, nontoxic, and as convenient as the "classic
      combination" of melphalan and prednisolone.

PMID- 10936871
TI  - Detection of occult cobalamin deficiency by magnetic resonance imaging.
AB  - We present a case of cobalamin deficiency in an elderly woman who presented with
      peripheral neuropathy without evidence of anemia or macrocytosis; her diagnosis
      was suspected with cervical magnetic resonance imaging. This imaging modality may
      identify patients with cobalamin deficiency who have neurologic abnormalities
      with normal hematologic parameters.

PMID- 10936872
TI  - Prolonged immunoglobulin and platelet infusion for treatment of immune
      thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) may be associated with serious hemorrhage. We
      describe 2 patients who received intravenous immunoglobulin given as a 24-hr
      continuous infusion with a concomitant continuous infusion of platelets. This
      regimen was rapidly effective in increasing platelet counts in both patients.

PMID- 10936873
TI  - Repeated efficacy of all-trans-retinoic acid in an acute promyelocytic leukemia
      patient.

PMID- 10936874
TI  - Coexistence of factor V 1691 G-A and factor V 4070 A-G mutation in turkish
      thromboembolic patients.

PMID- 10936875
TI  - Spontaneous regression of chronic lymphocytic leukemia and simultaneous
      development of autoimmune hemolytic anemia and autoimmune thrombocytopenia.

PMID- 10936876
TI  - Lipoproteins and related molecules in Alzheimer's disease.

PMID- 10936877
TI  - Apolipoprotein E gene promoter polymorphisms in Alzheimer's disease.
AB  - Alzheimer's disease, the most frequent form of senile dementia, presents in the
      vast majority of cases as a multifactorial trait, where a series of genetic and
      environmental risk factors converge. The increasing body of data, both
      epidemiological and functional, is strengthening the evidence that apolipoprotein
      E (APOE, gene; apoE, protein) is a true susceptibility factor for the onset of
      the common form of Alzheimer's disease. The E4 isoform of apoE remains to date as
      the main genetic risk factor for the disease, although the mechanisms responsible
      for this association are not well understood. It is also clear that apoE4 is not
      necessary or sufficient to cause the disease, indicating that other risk and
      protecting factors exist. ApoE is upregulated in response to nervous system
      injury, suggesting that it could have a neuroprotective role; on the other hand,
      there is evidence indicating that apoE is neurotoxic when present at high levels.
      Thus, apoE levels seem to be relevant for the functionality of the protein. The
      APOE proximal promoter hosts numerous regulatory elements, raising the
      possibility that polymorphisms in this region could produce variation in apoE
      levels by altering APOE transcriptional activity, which could finally result in
      AD susceptibility. We will review here the current evidence on the relationship
      between APOE proximal promoter polymorphisms, APOE gene transcriptional activity
      and apoE protein levels, and risk for AD.

PMID- 10936878
TI  - LDL receptor-related protein (LRP) in Alzheimer's disease: towards a unified
      theory of pathogenesis.
AB  - To date, mutations in three genes, beta-amyloid precursor protein (APP),
      presenilin 1 (PS1), and presenilin 2 (PS2), have been found to be causally
      related to familial Alzheimer's disease (AD). In addition, polymorphisms in three
      other genes (among others), apolipoprotein E (apoE), alpha2-macroglobulin
      (alpham), and the low density lipoprotein receptor-related protein (LRP), are
      implicated to contribute to AD pathogenesis. Interestingly, the encoded gene
      products are all functionally related in various ways to LRP. Specifically apoE,
      alpha2m, secreted APP, and amyloid beta-protein (Abeta) complexed to either apoE
      or alpha2m are ligands of LRP. Furthermore, over-expression of presenilin 1
      results in decreased expression of LRP. Since levels of many LRP ligands are
      increased in Alzheimer's disease and LRP and its ligands are present in senile
      plaques, decreased LRP function may be a central component in AD pathogenesis.
      This review explores the current knowledge of LRP in AD and its relationship to
      the other known AD susceptibility markers.

PMID- 10936879
TI  - Very low density lipoprotein receptor in Alzheimer disease.
AB  - The apolipoprotein (APO) E4 isoform is associated with an accelerated rate of
      Alzheimer disease (AD) expression in sporadic as well as late-onset familial
      forms of the disease but the precise mechanism is unknown. In an attempt to
      approach the possible mechanisms involved, APOE receptors have been studied. They
      all belong to the low density lipoprotein (LDL) receptor family and share the
      same structural motifs. Some of them are preferentially expressed in the brain
      such as the LDL receptor related protein, the apolipoprotein E receptor 2, and
      the very low density lipoprotein (VLDL) receptor. These receptors have been
      suspected to be involved in Alzheimer disease at various levels. Among them, the
      VLDL receptor was extensively explored. Although genetic studies conducted on a
      polymorphism in the promoter of the VLDL receptor in Japanese and Caucasian
      populations gave divergent results, this does not exclude a possible involvement
      of the VLDL receptor in AD.

PMID- 10936880
TI  - Apolipoprotein E isoforms in Alzheimer's disease pathology and etiology.
AB  - The apolipoprotein E (apoE) epsilon4 allele increases risk of Alzheimer's disease
      (AD), perhaps by accelerating plaque formation, or by impairing neuron repair.
      Considerable evidence supports both mechanisms. AD patients with epsilon4 have
      more and earlier amyloid deposits than do patients without epsilon4. The same is
      true of non-demented control subjects. In vitro, all apoE isoforms inhibit
      amyloid beta protein (Abeta) aggregation, but apoE4 less effectively than apoE3.
      Transgenic amyloid-producing mice expressing apoE3 or apoE4 develop less Abeta
      deposition than apoE knockout mice. These observations are consistent with an
      effect of apoE isoforms on Abeta aggregation in AD. ApoE is important for neurite
      maintenance since apoE knockout mice lose neurites and suffer behavioral deficits
      with aging or treatment with excitotoxins. ApoE4 mice show similar defects, but
      apoE3 mice are normal. AD patients with epsilon4 show more neuritic deficits than
      epsilon3 carriers. ApoE epsilon4 also worsens neurological impairment in head
      injury, stroke, and multiple sclerosis. Thus, apoE4 is less effective at neurite
      maintenance. Perhaps epsilon4 increases AD risk by both mechanisms: allowing
      amyloid deposition and failing to repair neurites. In either case, introducing
      apoE3 or apoE2 into the brain, for example by gene therapy or cell grafts, might
      delay AD progression.

PMID- 10936881
TI  - Cerebrospinal fluid lipoproteins in Alzheimer's disease.
AB  - Interest in cerebrospinal fluid (CSF) lipoproteins has been stimulated by the
      association of certain alleles of the human apolipoprotein E gene (APOE) with an
      increased risk of Alzheimer's disease (AD), and because apolipoprotein E (apoE)
      is one of the major apolipoproteins in CSF. CSF lipoproteins (d < 1.210 g/ml
      fraction) are distinct from their plasma counterparts, and in AD patients CSF may
      contain novel particles. The protein concentration of CSF lipoproteins is reduced
      in AD patients. Moreover, the molecular distribution of apoE- and apoAII
      containing apolipoproteins in CSF is dictated by APOE. The lipid composition
      suggests that CSF lipoproteins from AD patients may have undergone increased free
      radical-mediated damage; experimental data support the possibility that this may
      occur both before and after lipoprotein assembly. Finally, human CSF lipoproteins
      oxidized ex vivo are neurotoxic to neuronal cells in culture and disrupt
      microtubule structure, an activity not observed with oxidized bovine CSF
      lipoproteins. CSF lipoproteins may represent a means whereby apoE influences the
      outcome of free radical-mediated damage to brain.

PMID- 10936882
TI  - Link between heart disease, cholesterol, and Alzheimer's disease: a review.
AB  - Increased prevalence of Alzheimer's disease-like beta-amyloid deposits in the
      neuropil and within neurons occurs in the brains of non-demented individuals with
      heart disease. Heart disease is a prevalent finding in Alzheimer's disease, and
      may be a forerunner to the dementing disorder. In the cholesterol-fed rabbit
      model of human coronary heart disease there is production and accumulation of
      beta-amyloid in the brain. This accumulation of beta-amyloid can be reversed by
      removing cholesterol from the rabbits' diet. In culture cells, a cholesterol
      challenge has been shown to increase production of beta-amyloid, and dramatic
      reductions of cholesterol produced by HMG Co-A reductase inhibitors decrease
      production of beta-amyloid. Increased beta-amyloid production is also produced by
      dietary cholesterol in a number of transgenic mouse models of Alzheimer's
      disease. Administration of HMG Co-A reductase inhibitors may block beta-amyloid
      production caused by dietary cholesterol in rabbits. Clinical trials testing the
      benefit of HMG Co-A reductase inhibitors in the treatment of Alzheimer's disease
      are underway.

PMID- 10936883
TI  - Roles for lipoprotein lipase in Alzheimer's disease: an association study.
AB  - Lipoprotein lipase (LPL) assists lipid transport by transferring lipids between
      lipoprotein particles and cells. LPL binds apolipoprotein E (apoE) lipoprotein
      particles and a major apoE receptor, low density lipoprotein receptor related
      protein (LRP). Because apoE and LRP polymorphisms alter Alzheimer's disease (AD)
      risk, and LPL itself is found in AD amyloid plaques, we examined whether LPL
      variants also affect AD risk. In case-control studies in the United States and
      Canada, the frequencies of two LPL alleles known to affect LPL enzymatic activity
      were measured in Caucasian AD or elderly normal (N) subjects. Pathologically
      confirmed subjects in both studies exhibited similar trends toward fewer 447Ter
      and more 291Ser alleles in AD. Combining results from both countries gave allele
      frequencies for 447Ter of 13.7% (26/190) in N and 9.4% (80/852) in AD (P = 0.10),
      and for 291Ser of 0.0% (0/184) in N and 1. 3% (8/636) in AD (P = 0.21). The trend
      appeared even greater for homozygous 447Ter subjects: 4.2% (4/95) of N vs. 1.4%
      (6/426) of AD (P = 0.09). These trends are consistent with a putative protective
      effect of 447Ter and causative effect of 291Ser on AD. Furthermore, brains of AD
      patients with 447Ter showed trends toward fewer plaques, tangles, and glia, and
      more neurons and cortical thickness than AD patients without 447Ter. Hippocampal
      plaques were significantly reduced. LPL might affect hippocampal function and
      thus dementia via its role as supplier of membrane components or antioxidants to
      neurons. Alternatively, LPL may play a part in plaque formation through its
      interaction with apoE and LRP.

PMID- 10936884
TI  - Astrocyte lipoproteins, effects of apoE on neuronal function, and role of apoE in
      amyloid-beta deposition in vivo.
AB  - The genetic association between the E4 isoform of apolipoprotein E (apoE) and
      increased risk for Alzheimer's disease (AD) has prompted interest in the
      neurobiology of apoE and the possible relationship between lipoprotein metabolism
      in the brain and neurodegenerative disease. ApoE, a product of astrocytes, is
      abundant in brain and in cerebrospinal fluid (CSF) where it is found in
      lipoproteins the size of large plasma high-density lipoproteins (HDL). Cultured
      astrocytes also secrete apoE/HDL, although the lipid and apoprotein composition
      of these nascent particles differs from that found in CSF, suggesting possible
      functional differences. In vitro studies have demonstrated isoform-specific
      effects of apoE on neurite outgrowth, neuronal plasticity, neurotoxicity, lipid
      peroxidation, oxidative injury, binding to cytoskeletal proteins, and
      interactions with amyloid-beta (Abeta), a primary component of senile plaques in
      AD. A number of these proposed functions have also been assessed in apoE -/- mice
      and transgenic mice expressing human apoE3 or apoE4. Importantly, analysis of
      transgenic mice overexpressing a mutant form of the human amyloid precursor
      protein (APP(V717F)) in the presence of mouse apoE, no apoE, or human apoE3 or E4
      has demonstrated a critical and isoform-specific role for apoE in neuritic plaque
      formation, a pathologic hallmark of AD. Together, these data have provided
      important clues as to possible mechanism(s) by which apoE genotype modifies AD
      risk.

PMID- 10936885
TI  - Apolipoprotein J (clusterin) and Alzheimer's disease.
AB  - Apolipoprotein J (clusterin) is a ubiquitous multifunctional glycoprotein capable
      of interacting with a broad spectrum of molecules. In pathological conditions, it
      is an amyloid associated protein, co-localizing with fibrillar deposits in
      systemic and localized amyloid disorders. In Alzheimer's disease, the most
      frequent form of amyloidosis in humans and the major cause of dementia in the
      elderly, apoJ is present in amyloid plaques and cerebrovascular deposits but is
      rarely seen in NFT-containing neurons. ApoJ expression is up-regulated in a wide
      variety of insults and may represent a defense response against local damage to
      neurons. Four different mechanisms of action could be postulated to explain the
      role of apoJ as a neuroprotectant during cellular stress: (1) function as an anti
      apoptotic signal, (2) protection against oxidative stress, (3) inhibition of the
      membrane attack complex of complement proteins locally activated as a result of
      inflammation, and (4) binding to hydrophobic regions of partially unfolded,
      stressed proteins, and therefore avoiding aggregation in a chaperone-like manner.
      This review focuses on the association of apoJ in biological fluids with
      Alzheimer's soluble Abeta. This interaction prevents Abeta aggregation and
      fibrillization and modulates its blood-brain barrier transport at the
      cerebrovascular endothelium.

PMID- 10936887
TI  - Telepathology and other telemedicine fields: lessons to learn.

PMID- 10936886
TI  - Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta
      protein.
AB  - Amyloid beta-protein (Abeta), the major component of plaques in Alzheimer's
      disease, is a small hydrophobic protein that is carried on apolipoprotein E
      (ApoE)- and ApoJ-containing lipoprotein particles in plasma and cerebrospinal
      fluid (CSF). Microglia, the scavenger cells of the CNS, take up and degrade Abeta
      via lipoprotein receptors including scavenger receptors A and B, and possibly via
      other receptors. Lipoproteins, ApoE, and ApoJ influence the uptake and
      degradation of Abeta in vitro and in vivo. Differences in ApoE-E4, -E3, and -E2
      isoforms with respect to Abeta binding to lipoproteins and delivery to cells,
      including microglia, may contribute to the increased risk of Alzheimer's disease
      for people with an APOE4 genotype and to risk reduction with APOE2.

PMID- 10936888
TI  - The applications of FISH in tumor pathology.
AB  - The current FISH technology was greatly improved during the past 10 years. A
      large number of cosmids and yeast (YACs), bacterial (BACs), phage P1 derived
      (PACs) artificial chromosomes have been rapidly mapped and are useful as probes.
      In parallel, methods were established to specifically "paint" entire chromosomes
      or chromosome segments. Using these chromosome libraries as probes, complex
      rearrangements and marker chromosomes can be identified irrespective of their
      banding pattern. Ripetitive DNA probes specific for each chromosome centromere
      (alpha satellite sequences), are also available and may be used to identify
      specific aneuploidies. The use of sensitive digital imaging systems on the basis
      of "colour" rather than morphology increased the improvement of new FISH
      techniques. In particular, colour karyotyping results in the differential colour
      display of all human chromosomes. Another recent development of FISH technology
      is comparative genome hybridization (CGH), a genome-scanning technique that
      allows to identify and map chromosomal and subchromosomal gains and losses. FISH
      techniques may be used to investigate chromosome abnormalities not only on
      metaphasic chromosomes but also on interphasic nuclei. Any given tissue or cell
      source, such as sections of frozen tumors, imprinted cells, cultured cells,
      paraffin-embedded sections may be hybridized. The interphasic FISH may be
      extremely informative in tumor pathology even if the results are dependent on a
      good technical quality and adequate controls.

PMID- 10936889
TI  - p27 Expression, a cyclin dependent kinase inhibitor in breast carcinoma.
AB  - p27 KIP1 is a cyclin dependent kinase inhibitor, which may act as a potential
      suppressor gene. Several lines of evidence support the hypothesis that reduced
      p27 KIP1 expression is related to uncontrolled cell proliferation and
      tumorigenesis. Low immunohistochemical expression of p27 KIP1 in human neoplasm
      seems related to tumor progression and poor prognosis. In breast cancer, low p27
      is associated with high tumour grade and loss of oestrogen receptor, and it has
      been suggested that low p27 KIP1 is a powerful and independent prognostic marker
      of poor clinical outcome. There are however some discrepant results: a few
      studies, some of which conducted on large series of patients, do not support an
      independent role of p27 KIP1 as a prognostic marker. We are indeed faced with an
      intriguing hypothesis, but many more studies are needed to evaluate the real
      value of p27 KIP1 as a prognostic marker.

PMID- 10936890
TI  - Changes in the normal-looking epithelium in prostates with PIN or cancer.
AB  - BACKGROUND: In prostatic neoplasia, the time from tumour initiation and
      progression to invasive carcinoma often begins in men in the fourth and fifth
      decades of life and extends across decades. Until recently, the events initiating
      the process and the developments concomitant with the evolution towards invasive
      disease were largely unknown. METHODS: Quantitative and analytical methods are
      applied to provide insights into certain individual molecular events and their
      effects on the complex multiple feedback system of cellular metabolism and
      regulation in prostate neoplasia. RESULTS: Prostatic intraepithelial neoplasia
      (PIN) and prostate cancer (PCa) are associated with or possibly preceded by
      changes in the chromatin of secretory cell nuclei. The changes are detectable
      with a Bayesian belief network and quantifiable by computer image analysis in
      prostatic tissue that still appears histologically normal. In addition, normal
      looking prostate epithelium shows some molecular changes similar to those present
      in the associated preneoplastic and neoplastic lesions. Such changes are also
      occasionally present in normal prostate glands without PIN and cancer.
      CONCLUSIONS: The subtle morphological and molecular changes of normal looking
      epithelium might be seen as the onset of the development of prostatic neoplasia.

PMID- 10936891
TI  - Lymph node revealing solution: is it effective on detecting minute lymph nodes?
AB  - AIMS: The aim of this prospective study is to detect the efficiency of a
      previously described lymph node revealing solution (LNRS) in comparing with
      conventional lymph node dissection and re-dissection in colon, breast and urinary
      bladder carcinomas. METHODS: Total 30 cases in which less than 10 lymph nodes
      were found by conventional method, were immersed for 6-8 hours in LNRS, dissected
      and processed. Control group, 12 cases, was first dissected then a second
      conventional dissection was performed. At the end, specimens were again immersed
      in LNRS for 6-8 hours and last dissections were done. MAIN RESULTS: In the first
      group, a total of 150 lymph nodes, 46 of them with metastasis were detected.
      After using LNRS, 26 additional lymph nodes among which 10 were positive were
      detected. When compared with the results of conventional dissection, the increase
      in number of total and metastatic lymph nodes with LNRS was significant (p<0.01).
      The mean size of the lymph nodes detected by the conventional and LNRS methods
      was 6.8 and 4.2 mm, respectively. The pathologic lymph node stage was changed in
      three bladder carcinoma cases, and one breast carcinoma. In the control group, 75
      lymph nodes (11 with metastases), 19 lymph nodes (3 with metastases), 14 lymph
      nodes (one with metastases) were detected after first and second conventional
      dissection and LNRS methods, respectively. CONCLUSION: LNRS enhanced the number
      of total and metastatic lymph nodes and is effective in detecting small lymph
      nodes. This method is useful for accurate staging where the number of detected
      lymph nodes is too small by the conventional method.

PMID- 10936892
TI  - Focal nodular hyperplasia of the liver associated with portal vein agenesis: a
      morphological and immunohistochemical study of one case and review of the
      literature.
AB  - Congenital absence of portal vein (CAPV) is a rare malformation. To our
      knowledge, sixteen cases are reported in western literature. All the cases are
      associated with other diseases, cardiac malformations (12/17 patients; 16 plus
      the present case) and hepatic neoplasms being the most frequent observations. We
      present the case of a girl with a complex malformative syndrome consisting of
      multicystic kidney dysplasia, CAPV and nodular tumor-like mass of the liver.
      Angiography showed that the splenic vein and superior mesenteric vein joined to
      form a common trunk directly entering the inferior vena cava above the liver. A
      review of the CAPV cases of the literature and the clinical and pathological
      features of the hepatic lesion, classified as Focal Nodular Hyperplasia (FNH),
      are extensively discussed.

PMID- 10936893
TI  - Clinicians, diagnosis and clinical decision making: the importance of an evidence
      based approach. Part I. Introduction to evidence based medicine and how to search
      for it.

PMID- 10936894
TI  - Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach.
AB  - The authors have hypothesized that dietary iodine (deficiency or excess) is
      associated with the development of some gastric and mammary cancers, as it is
      well-known for thyroid cancer. They report a short review of their own work and
      of the general literature on this correlation and on the antioxidant function of
      iodide in stomach, breast and thyroid. Thyroid cells phylogenetically derived
      from primitive iodide-concentrating gastroenteric cells which, during evolution,
      migrated and specialized in uptake and storage of iodine, also in order to adapt
      the organisms from iodine-rich sea to iodine-deficient land. Mammary cells also
      derived from primitive iodide-concentrating ectoderm. Stomach, breast and thyroid
      share an important iodide-concentrating ability and an efficient peroxidase
      activity, which transfers electrons from iodides to the oxygen of hydrogen
      peroxide and so protects the cells from damage caused by lipid peroxidation. The
      authors suggest that iodide might have an ancestral antioxidant function in all
      iodide-concentrating cells from primitive Algae to more recent Vertebrates. In
      Italy, gastric cancer is more frequent in farmers and in iodine-deficient
      populations, living in mountainous and hilly areas, than in fishermen. In the
      last two decades, Italian decrease of gastric cancer seems to be correlated more
      to the higher dietary consumption of iodine-rich fish rather than to consumption
      of fruit and vegetables, which indeed has decreased in Italy.

PMID- 10936895
TI  - Detection of bladder cancer by semi-automated microsatellite analysis of urine
      sediment.
AB  - Patients with transitional-cell carcinoma (TCC) require careful follow-up due to
      the high risk of recurrence. Cystoscopy and biopsy are reliable but invasive,
      while urine cytology is plagued by low sensitivity. It has recently been shown
      that allelic abnormalities detected by microsatellite analysis of DNA extracted
      from urine can be used to diagnose TCC with high reliability. As this analysis by
      classic techniques is unfeasible in a clinical setting, we performed a pilot
      study to determine the possibility of applying quick DNA extraction methods with
      laser detection and computer-based analysis of 15 fluorescently labeled PCR
      amplified microsatellites to detect molecular anomalies in urine sediment in 25
      TCC follow-up patients. Of the eighteen cases with recurrent TCC, 14 (78%) were
      positive by the molecular test whereas only eight (44%) were detected by
      cytology. Of the seven patients with negative cystoscopy, one resulted positive
      by the molecular test and had recurrent TCC six-months later. Thus, this
      microsatellite analysis correctly predicted the clinical diagnosis in 84% (21/25)
      of cases, compared to 60% by cytology. The application of these semi-automated
      procedures allows the analysis of 18 samples with 15 markers in one day,
      encouraging a more expedient introduction into routine clinical use.

PMID- 10936896
TI  - Perineuroma. A frequently unrecognized entity with emphasis on a plexiform
      variant.
AB  - AIMS: The present series describes six cases of perineurioma, a rare and
      frequently unrecognized entity, including one case with an unusual plexiform
      growth pattern. METHODS: Retrospective clinicopathologic study of six
      perineuriomas. RESULTS: All lesions occurred on the upper extremities or
      shoulders of adults, five in females. Histologically, all six cases of
      perineurioma had been initially unrecognized or misdiagnosed as dermatofibroma,
      fibroma of tendon sheath, neurofibroma, schwannoma, or naevus, respectively.
      Scanning magnification revealed well circumscribed, dermal to subcutaneous
      lesions without capsule formation. Besides characteristic onion bulbs", i.e.
      concentric whorls of epithelioid to spindle-shaped cells, there was great
      variation of histomorphologic features: single nodules or plexiform architecture;
      a few to many concentric whorls; five to several dozens of cell layers in
      concentric whorls; high to low cellularity; round/oval to spindle-shaped/wavy
      cells/nuclei; delicate to prominent collagen; variable mucin, sclerosis, and/or
      intralesional clefts. Immunohistochemically, all lesions were consistently
      positive for EMA, ultrastructurally (1 case) with evidence of perineurial
      differentiation such as slender and elongated, bipolar cytoplasmic processes with
      discontinuous basal lamina, prominent pinocytosis and desmosome-like junctions.
      CONCLUSION: Our series documents that cutaneous and subcutaneous perineurioma is
      frequently unrecognized or misinterpreted and may occasionally show a plexiform
      growth pattern. The differential diagnosis of plexiform variants includes a
      variety of plexiform lesions such as naevi, neurofibroma, schwannoma, etc.
      Historically, similar plexiform lesions seem to have been published as nerve
      sheath myxoma/neurothekeoma, Pacinian neurofibroma or perineurial myxoma. This
      terminology is imprecise and confusing and, thus, should be avoided in favour of
      the correct term of perineurioma.

PMID- 10936897
TI  - Primary pulmonary meningioma may arise from meningothelial-like nodules.
AB  - A rare case of primary pulmonary meningioma, associated with meningothelial-like
      nodules in the same lung resection, with preoperative fine needle aspiration
      cytological findings and ultrastructural features, is described. The simultaneous
      presence of meningioma and meningothelial-like nodules, never before described,
      corroborates the unifying hypothesis of their common origin and nature.

PMID- 10936898
TI  - Papillary renal carcinoma (clear cell type) arising in the escretory urothelial
      district: a very unusual feature.
AB  - A case of renal cell carcinoma, clear cell type, originating from the calyceal
      renal mucosa, is described.

PMID- 10936899
TI  - Sarcopenia: current perspectives.
AB  - The development of sarcopenia is a complex multi-factorial process which begins
      in mid-life and accelerates after the age of 75 years. Although exercise,
      nutritional supplementation, hormone replacement and pro-inflammatory cytokine
      therapy may improve health status and reduce mortality, a better understanding of
      the complex interactions between these factors are needed. This review will focus
      on current information regarding the roles that physical activity, hormonal
      changes, energy intake, oxidative stress, and inflammatory processes play on the
      development and progression of sarcopenia.

PMID- 10936900
TI  - Sarcopenia: a major modifiable cause of frailty in the elderly.
AB  - Sarcopenia is the loss of muscle mass and strength that occurs with aging. It is
      a consequence of normal aging, and does not require a disease to occur, although
      muscle loss can be accelerated by chronic illness. Sarcopenia is a major cause of
      disability and frailty in the elderly. There are many candidate mechanisms
      leading to sarcopenia, including age-related declines in alpha-motor neurons,
      growth hormone production, sex steroid levels, and physical activity. In
      addition, fat gain, increased production of catabolic cytokines, and inadequate
      intake of dietary energy and protein are also potentially important causes of
      sarcopenia. The relative contribution of each of these factors is not yet clear.
      Sarcopenia can be reversed with high-intensity progressive resistance exercise,
      which can probably also slow its development. A major challenge in preventing an
      epidemic of sarcopenia-induced frailty in the future is developing public health
      interventions that deliver an anabolic stimulus to the muscle of elderly adults
      on a mass scale.

PMID- 10936901
TI  - Strength training for the prevention and treatment of sarcopenia.
AB  - There is a progressive loss of muscle strength, muscle mass and muscle quality
      with advanced age, which results in a condition known as sarcopenia. In this
      review, the authors outline the magnitude of these losses, their functional
      consequences, and the efficacy of strength training (ST) as an intervention
      strategy for delaying, preventing or reversing the effects of sarcopenia. The
      question of whether sex differences and genetics influence the effects of
      sarcopenia and responses to ST are also discussed. Although many potential
      mechanisms for sarcopenia exist, their specific contributions are still unknown.
      Nevertheless, proposed mechanisms of sarcopenia are outlined and, where
      information is available, we examine the effects of ST on these potential
      mechanisms, which include neurogenic factors, anabolic hormones, protein
      synthesis, gene expression, muscle morphology, and muscle regeneration. Finally,
      the potential impact of genetics in the muscle response to both sarcopenia and ST
      is discussed. The evidence presented suggests that ST is an effective
      intervention for improving strength, muscle mass and muscle quality and delaying
      the onset of physical disability in the elderly. However, sex differences and
      genetic factors may play an important role in determining the muscular response
      to aging and ST.

PMID- 10936902
TI  - Sarcopenia and muscle function during menopause and hormone-replacement therapy.
AB  - Menopause and the loss of estrogen trigger a deleterious cascade of metabolic and
      cardiovascular events. Recent data suggest that the menopause transition is
      associated with changes in body composition that promote a loss of fat-free mass
      and potentially a decline in skeletal muscle mass that may be related to a
      decline in energy expenditure, a loss of muscular strength and a decline in
      physical activity. The mechanisms underlying changes in ovarian function and its
      influence on skeletal muscle mass, however, are unknown. This brief review
      examines the impact of the menopause transition on body composition with a
      particular emphasis on menopause-associated sarcopenia. We also consider the
      possibility that hormone-replacement may be an effective intervention to offset
      these changes.

PMID- 10936903
TI  - Regulation of excitation contraction coupling by insulin-like growth factor-1 in
      aging skeletal muscle.
AB  - Excitation-contraction (EC) uncoupling is a primary muscle alteration and
      constitutes a major cause of decline in skeletal muscle force with aging. The
      structural substratum for EC uncoupling in muscles from aging mammals is a
      reduction in number of dihydropyridine receptors (DHPR) at the T-tubule and SR
      membrane leading to an increase in the percent of sarcoplasmic reticulum calcium
      release channels or ryanodine receptors (RyR1) uncoupled to DHPR. The main
      functional consequence of this alteration is a failure in the transduction of
      sarcolemmal depolarization into a calcium signal and a mechanical response. This
      review summarizes recent studies from our laboratory aimed at elucidating the
      modulation of EC coupling by insulin-like growth factor-1 (IGF-1) in skeletal
      muscle. We demonstrated that transgenic overexpression of human IGF-1 exclusively
      in skeletal muscle increases the number and prevents age-related decline in the
      number of DHPR. IGF-1 enhances rat skeletal muscle DHPR function and gene
      expression. The functional significance of these findings is that IGF-1 prevents
      the age-related decline in muscle force.

PMID- 10936904
TI  - Determination of appendicular muscle mass by dual energy X-ray absorptiometry
      method in women with sarcopenia and Alzheimer's disease.
AB  - OBJECTIVES: To study appendicular muscle mass in women with Alzheimer's disease
      (AD) to investigate the association between sarcopenia and AD. To examine the AD
      associated changes in body fat distribution. DESIGN: a cross-sectional study of
      32 women with AD and 32 healthy age and bone mineral density matched women.
      SETTING: Toulouse, France. RESULTS: No differences were noted in fat free soft
      tissue mass or Appendicular Skeletal Muscle (ASM) mass between AD women and
      control women. The difference of ASM (kg) /height2 (m)2, used as an index of
      relative skeletal muscle mass, was not statistically significative between the
      two groups. The prevalence of sarcopenia increased from 21.9 % in healthy elderly
      women to 40.6 % in AD women but the difference was not statistically significant.
      No statistically significant relationship emerged between sarcopenia and AD (OR=
      0.41, CI 0.12-1.4). Moreover, total body fat mass was significantly lower in
      women with AD than in the age -, sex - and bone mineral density - matched
      controls. CONCLUSION: AD are not necessary linked to sarcopenia. The decrease in
      adipose tissue in women with AD could be one more factor involving estrogen
      deficiency in the etiology of the disease.

PMID- 10936905
TI  - Regulation of energy intake in older adults: recent findings and implications.
AB  - Inadequate energy intake is common in older individuals and is probably the major
      cause of unexplained weight loss. This summary highlights recent studies on
      possible causes of negative energy balance in older individuals suggesting that
      aging is associated with a significant impairment in the regulation of food
      intake that inhibits appropriate short-term and long-term compensation for normal
      fluctuations in energy intake. The combination of a reduced ability to regulate
      energy intake, decreased dietary variety, and disadvantageous social factors such
      as functional limitations, social isolation and depression, increases the risk of
      negative energy balance leading to weight loss in older individuals.

PMID- 10936906
TI  - The effects of lipids on the immune response of patients with cancer.
AB  - The role of diet and certain nutritional factors in the etiology or promotion of
      various malignant diseases has widely been studied. A link between dietary fat
      and cancer has long been proposed through various human epidemiologic and
      experimental data. High fat diets are associated with a high incidence and
      accelerated development of certain tumors, while there is evidence that dietary w
      3 fatty acids have beneficial effects in cancer growth and metastasis. The
      relation between the different lipid formulations and cancer appears to be mainly
      related to the influence of specific fatty acids on the synthesis of the
      immunosuppressive prostaglandin E2. Omega-3 polyunsaturated fatty acids seem to
      have an anti-tumor effect through their immunomodulating, anti-inflammatory
      action and direct inhibition of tumor cell proliferation via alteration in
      prostaglandin E2 production.

PMID- 10936907
TI  - Clinical usefulness of the mini nutritional assessment (MNA) scale in geriatric
      medicine.
AB  - OBJECTIVE: This study was undertaken to estimate the prevalence of malnutrition
      in elderly patients hospitalized with an acute illness, as well as to assess the
      clinical usefulness of standardized nutritional assessment upon admission by
      means of the MNA scale. DESIGN: A prospective study. SETTING: A large size
      regional university hospital. SUBJECTS: There were 175 patients (113 women and 62
      men) with a mean age of 79.7 + 8.5 years admitted for an acute problem. Death
      occurred in 11 patients (6.3%). METHODS: Upon admission, demographic (age,
      gender, origin) and medical (disease, drugs) data were recorded for each patient;
      the MNA questionnaire (score: 0-30) was administered and Katz score (7-28)
      calculated. At hospital discharge, data included Katz score, outcome
      (death/survival), and destination. RESULTS: The mean MNA score was 20.5 + 5.1 and
      the prevalence of severe malnutrition (MNA <17) was 21.7%. Further, 48.6% of
      elderly were at risk of malnutrition (MNA between 17 and 24). There was no
      association between MNA and age or gender, but underweight was a sign of low MNA
      values (P <.001). MNA scores were inversely related to Katz scores at both
      admission and hospital discharge (P <.001). Patients originating from nursing
      homes had a poorer nutritional status than those living at home (MNA: 18.4
      against 22.3, P <.001). The number of drugs taken per patient (5.2 + 2.8) was
      found to be correlated with MNA (P =.049). MNA scores were on average
      significantly higher (P <.001) in survivors (20.9) than in nonsurvivors (14.1).
      CONCLUSIONS: The study clearly demonstrates the high prevalence of malnutrition
      and the clinical usefulness of the MNA scale in geriatric medicine. The MNA score
      upon admission reflects the patient's nutritional condition, degree of autonomy
      (Katz score), living conditions and current treatment. It is also predictive of
      patient's outcome (death or survival).

PMID- 10936908
TI  - Effects of age and dietary restriction on lifespan and oxidative stress of SAMP8
      mice with learning and memory impairments.
AB  - This study was to evaluate the effect of dietary restriction (DR) on lifespan and
      oxidative stress of dementia mouse model SAMP8 with impaired learning and memory.
      SAMP8 female mice were fed either ad libitum (AL) or fed 60% of food intake of
      AL. Results showed that basal metabolic rates (BMR) were significantly lower (15
      to 22%) in DR with increased median and maximum lifespans, suggesting feed and
      gross efficiencies were significantly lower in DR than in AL. Grading score of
      senescence resulted in a marked improvement about 2-fold by DR compared with AL.
      The amounts of lipofuscin at 12 months were significantly lowered 16% in DR than
      that of AL. Median and maximal lifespans significantly increased (28.5% and
      16.4%, respectively) by DR, and also lowered superoxide radical about 15
      approximately 45% in DR compared with AL at 4, 8 and 12 months of age. On the
      other hand, superoxide dismutase (SOD) activities were higher (about 15
      approximately 30%) in DR than those in AL group of SAMP8 except for 4 months of
      age. Our results suggest that 40% calorie restricted SAMP8 can effectively
      suppress dementia-related abnormalities during aging.

PMID- 10936909
TI  - Neuromagnetic correlates of sensorimotor synchronization.
AB  - Sensorimotor synchronization tasks, in which subjects have to tap their finger in
      synchrony with an isochronous auditory click, typically reveal a synchronization
      error with the tap preceding the click by about 20 to 50 msec. Although extensive
      behavioral studies and a number of different explanatory accounts have located
      the cause of this so-called "negative asynchrony" on different levels of
      processing, the underlying mechanisms are still not completely understood. Almost
      nothing is known about the central processes, in particular, which sensory or
      motor events are synchronized by subjects. The present study examined central
      level processing in synchronization tasks with magnetoencephalography (MEG).
      Eight subjects synchronized taps with their right index finger to an isochronous
      binaural pacing signal presented at an interstimulus interval of 800 msec. To
      gain information on central temporal coupling between "tap" and "click," evoked
      responses were averaged time-locked to the auditory signal and the tap onset. Tap
      related responses could be explained with a three dipole model: One source,
      peaking at approximately 77 msec before tap onset, was localized in contralateral
      primary motor cortex (MI); the two other sources, peaking approximately at tap
      onset and 75 msec after tap onset, in contralateral primary somatosensory cortex
      (SI). Temporal coupling of these sources was compared in relation to different
      trigger points. The second SI source was equally well time-locked to the tap and
      to the auditory click. Furthermore, analysis of the time locking of this source
      activity as a function of the temporal order of tap and click showed that the
      second event - irrespective whether tap or click - was decisive in triggering the
      second SI source. This suggests that subjects use mainly sensory feedback in
      judging and evaluating whether they are "keeping time."

PMID- 10936910
TI  - Syntactic gender and semantic expectancy: ERPs reveal early autonomy and late
      interaction.
AB  - This experiment explored the effect of semantic expectancy on the processing of
      grammatical gender, and vice versa, in German using event-related-potentials
      (ERPs). Subjects were presented with correct sentences and sentences containing
      an article-noun gender agreement violation. The cloze probability of the nouns
      was either high or low. ERPs were measured on the nouns. The low-cloze nouns
      evoked a larger N400 than the high-cloze nouns. Gender violations elicited a left
      anterior negativity (LAN, 300-600 msec) for all nouns. An additional P600
      component was found only in high-cloze nouns. The N400 was independent of the
      gender mismatch variable; the LAN was independent of the semantic variable,
      whereas an interaction of the two variables was found in the P600. This finding
      indicates that syntactic and semantic processes are autonomous during an early
      processing stage, whereas these information types interact during a later
      processing phase.

PMID- 10936911
TI  - Modulation of spatial orientation processing by mental imagery instructions: a
      MEG study of representational momentum.
AB  - Under appropriate conditions, an observer's memory for the final position of an
      abruptly halted moving object is distorted in the direction of the represented
      motion. This phenomenon is called "representational momentum" (RM). We examined
      the effect of mental imagery instructions on the modulation of spatial
      orientation processing by testing for RM under conditions of picture versus body
      rotation perception and imagination. Behavioral data were gathered via classical
      reaction time and error measurements, whereas brain activity was recorded with
      the help of magnetoencephalography (MEG). Due to the so-called inverse problem
      and to signal complexity, results were described at the signal level rather than
      with the source location modeling. Brain magnetic field strength and spatial
      distribution, as well as latency of P200m evoked fields were used as
      neurocognitive markers. A task was devised where a subject examined a rotating
      sea horizon as seen from a virtual boat in order to extrapolate either the
      picture motion or the body motion relative to the picture while the latter
      disappeared temporarily until a test-view was displayed as a final orientation
      candidate. Results suggest that perceptual interpretation and extrapolation of
      visual motion in the roll plane capitalize on the fronto-parietal cortical
      networks involving working memory processes. Extrapolation of the rotational
      dynamics of sea horizon revealed a RM effect simulating the role of gravity in
      rotational equilibrium. Modulation of the P200m component reflected spatial
      orientation processing and a non-voluntary detection of an incongruity between
      displayed and expected final orientations given the implied motion. Neuromagnetic
      properties of anticipatory (Contingent Magnetic Variation) and evoked (P200m)
      brain magnetic fields suggest, respectively, differential allocation of
      attentional resources by mental imagery instructions (picture vs. body tilt), and
      a communality of neural structures (in the right centro-parietal region) for the
      control of both RM and mental rotation processes. Finally, the RM of the body
      motion is less prone to forward shifts than that of picture motion evidencing an
      internalization of the implied mass of the virtual body of the observer.

PMID- 10936912
TI  - Auditory and visual spatial localization deficits following bilateral parietal
      lobe lesions in a patient with Balint's syndrome.
AB  - Lesion and electrophysiological studies indicate that the parietal lobes play a
      role in visual spatial attention and in computing the spatial coordinates of
      visual input. Fewer studies have investigated the role of the parietal lobe in
      auditory spatial processing, and an extensive comparison of visual and auditory
      spatial processing in humans with parietal lobe lesions has yet to be conducted.
      We have studied such localization abilities in a Balint's syndrome patient (RM)
      who has bilateral parietal lobe lesions. The results indicated that this patient
      had a significant deficit in both visual and auditory localization relative to
      age-matched controls. Unlike the controls, however, RM's auditory localization
      ability either matched or exceeded his visual localization ability depending on
      the task. Accordingly, RM exhibited "auditory capture," but not "visual capture"
      under conditions where control subjects showed the opposite pattern. These
      results are consistent with hypotheses that the parietal lobes are involved in
      creating multiple spatial representations and in shifting from one spatial
      reference point to another, but suggest that these parietal structures are not
      necessary for the integration of multiple sensory stimuli resulting in capture
      effects.

PMID- 10936913
TI  - Models of the posterior parietal cortex which perform multimodal integration and
      represent space in several coordinate frames.
AB  - Many neurons in the posterior-parietal cortex (PPC) have saccadic responses to
      visual and auditory targets. The responses are modulated by eye position and head
      position. These findings suggest that PPC integrates multisensory inputs and may
      provide information about saccadic targets represented in different coordinate
      frames. In addition to an eyecentered output representation, PPC may also project
      to brain areas which contain head-centered and body-centered representations of
      the space. In this report, possible coordinate transformations in PPC were
      examined by comparing several sets of models of PPC, each having different
      representations in the output layer: (i) an eye-centered map only; (ii) a head
      centered map only; (iii) an eye-centered map and a head-centered map; and (iv) an
      eye-centered map, a head-centered map, and a body-centered map. These output maps
      correctly encoded saccades to visual and auditory targets through training. The
      units in the hidden layers of the models exhibited the following properties: (1)
      The units had gain fields (GFs) for eye position, and also for head position if
      the model had a body-centered output representation; (2) As the result of the GF
      and the nonlinear activation function of the units, the hidden layers often
      employed "intermediate" coding, e.g., the hidden units coded targets partially in
      eye-centered coordinates and, partially, in head-centered coordinates; (3)
      Different types of coordinate transformations in these models were carried out by
      different relationships between the receptive fields (RFs) and the GFs of the
      hidden units; and (4) The properties of PPC neurons are in better accordance with
      the hidden units of the models that had multiple-output representations than the
      models that had only one single-output representation. In conclusion, the results
      show that the GF is an effective mechanism for performing coordinate
      transformations. The models also suggest that neurons with intermediate coding
      are to be expected in the process of coordinate transformations.

PMID- 10936914
TI  - Activation timecourse of ventral visual stream object-recognition areas: high
      density electrical mapping of perceptual closure processes.
AB  - Object recognition is achieved even in circumstances when only partial
      information is available to the observer. Perceptual closure processes are
      essential in enabling such recognitions to occur. We presented successively less
      fragmented images while recording high-density event-related potentials (ERPs),
      which permitted us to monitor brain activity during the perceptual closure
      processes leading up to object recognition. We reveal a bilateral ERP component
      (N(cl)) that tracks these processes (onsets approximately 230 msec, maximal at
      approximately 290 msec). Scalp-current density mapping of the N(cl) revealed
      bilateral occipito-temporal scalp foci, which are consistent with generators in
      the human ventral visual stream, and specifically the lateral-occipital or LO
      complex as defined by hemodynamic studies of object recognition.

PMID- 10936915
TI  - Brain activation during reading in deep dyslexia: an MEG study.
AB  - Magnetoencephalographic (MEG) changes in cortical activity were studied in a
      chronic Finnish-speaking deep dyslexic patient during single-word and sentence
      reading. It has been hypothesized that in deep dyslexia, written word recognition
      and its lexical-semantic analysis are subserved by the intact right hemisphere.
      However, in our patient, as well as in most nonimpaired readers, lexical-semantic
      processing as measured by sentence-final semantic-incongruency detection was
      related to the left superior-temporal cortex activation. Activations around this
      same cortical area could be identified in single-word reading as well. Another
      factor relevant to deep dyslexic reading, the morphological complexity of the
      presented words, was also studied. The effect of morphology was observed only
      during the preparation for oral output. By performing repeated recordings 1 year
      apart, we were able to document significant variability in both the spontaneous
      activity and the evoked responses in the lesioned left hemisphere even though at
      the behavioural level, the patient's performance was stable. The observed
      variability emphasizes the importance of estimating consistency of brain activity
      both within and between measurements in brain-damaged individuals.

PMID- 10936916
TI  - Electrophysiological correlates of phonological processing: a cross-linguistic
      study.
AB  - It is well known that speech perception is deeply affected by the phoneme
      categories of the native language. Recent studies have found that phonotactics,
      i.e., constraints on the cooccurrence of phonemes within words, also have a
      considerable impact on speech perception routines. For example, Japanese does not
      allow (nonnasal) coda consonants. When presented with stimuli that violate this
      constraint, as in / ebzo/, Japanese adults report that they hear a /u/ between
      consonants, i.e., /ebuzo/. We examine this phenomenon using event-related
      potentials (ERPs) on French and Japanese participants in order to study how and
      when the phonotactic properties of the native language affect speech perception
      routines. Trials using four similar precursor stimuli were presented followed by
      a test stimulus that was either identical or different depending on the presence
      or absence of an epenthetic vowel /u/ between two consonants (e.g., "ebuzo ebuzo
      ebuzo- ebzo"). Behavioral results confirm that Japanese, unlike French
      participants, are not able to discriminate between identical and deviant trials.
      In ERPs, three mismatch responses were recorded in French participants. These
      responses were either absent or significantly weaker for Japanese. In particular,
      a component similar in latency and topography to the mismatch negativity (MMN)
      was recorded for French, but not for Japanese participants. Our results suggest
      that the impact of phonotactics takes place early in speech processing and
      support models of speech perception, which postulate that the input signal is
      directly parsed into the native language phonological format. We speculate that
      such a fast computation of a phonological representation should facilitate
      lexical access, especially in degraded conditions.

PMID- 10936917
TI  - Volitional covert orienting to a peripheral cue does not suppress cue-induced
      inhibition of return.
AB  - Detection reaction time (RT) at an extrafoveal location can be increased by
      noninformative precues presented at that location or ipsilaterally to it. This
      cue-induced inhibition is called inhibition of return or ipsilateral inhibition.
      We measured detection RT to simple light targets at extrafoveal locations that
      could be designated for covert orienting by local or distant cues. We found that
      cue-induced inhibition cooccurred in an additive fashion with the direct effects
      of covert orienting, i.e., it detracted from facilitation at attended locations
      and increased the disadvantage for unattended locations. Thus, cue-induced
      inhibition cannot be suppressed by a volitional covert orienting to the cued
      location; the co-occurrence of different facilitatory and inhibitory effects
      confirms the simultaneous operation of multiple independent attentional
      mechanisms during covert orienting.

PMID- 10936918
TI  - Electrophysiological evidence for the modulation of retrieval orientation by
      depth of study processing.
AB  - Event-related potentials (ERPs) were employed to investigate whether brain
      activity elicited by retrieval cues in a memory test varies according to the
      encoding task undertaken at study. Two recognition memory test blocks were
      administered, preceded, in one case, by a "shallow" study task (alphabetic
      judgement) and, in the other case, by a "deep" task (sentence generation). ERPs
      elicited by the new words in each test block differed, the ERPs elicited in the
      block following the shallow study task exhibiting the more positive-going
      waveforms. This finding was taken as evidence that subjects adopt different
      "retrieval sets" when attempting to retrieve items that had been encoded in terms
      of alphabetic versus semantic attributes. Differences between the ERPs elicited
      by correctly classified old and new words (old/new effects) also varied with
      encoding task. The effects for deeply studied words resembled those found in
      previous ERP studies of recognition memory, whereas old/new effects for shallowly
      studied words were confined to a late-onsetting, right frontal positivity.
      Together, the findings indicate that the depth of study processing influences two
      kinds of memory-related neural activity, associated with memory search
      operations, and the processing of retrieved information, respectively.

PMID- 10936919
TI  - The role of segmentation in phonological processing: an fMRI investigation.
AB  - Phonological processes map sound information onto higher levels of language
      processing and provide the mechanisms by which verbal information can be
      temporarily stored in working memory. Despite a strong convergence of data
      suggesting both left lateralization and distributed encoding in the anterior and
      posterior perisylvian language areas, the nature and brain encoding of
      phonological subprocesses remain ambiguous. The present study used functional
      magnetic resonance imaging (fMRI) to investigate the conditions under which
      anterior (lateral frontal) areas are activated during speech-discrimination tasks
      that differ in segmental processing demands. In two experiments, subjects
      performed "same/ different" judgments on the first sound of pairs of words. In
      the first experiment, the speech stimuli did not require overt segmentation of
      the initial consonant from the rest of the word, since the "different" pairs only
      varied in the phonetic voicing of the initial consonant (e.g., dip-tip). In the
      second experiment, the speech stimuli required segmentation since "different"
      pairs both varied in initial consonant voicing and contained different vowels and
      final consonants (e.g., dip-ten). These speech conditions were compared to a tone
      discrimination control condition. Behavioral data showed that subjects were
      highly accurate in both experiments, but revealed different patterns of reaction
      time latencies between the two experiments. The imaging data indicated that
      whereas both speech conditions showed superior temporal activation when compared
      to tone discrimination, only the second experiment showed consistent evidence of
      frontal activity. Taken together, the results of Experiments 1 and 2 suggest that
      phonological processing per se does not necessarily recruit frontal areas. We
      postulate that frontal activation is a product of segmentation processes in
      speech perception, or alternatively, working memory demands required for such
      processing.

PMID- 10936920
TI  - Tickling expectations: neural processing in anticipation of a sensory stimulus.
AB  - Predictions of the near future can optimize the accuracy and speed of sensory
      processing as well as of behavioral responses. Previous experience and contextual
      cues are essential elements in the generation of a subjective prediction. Using a
      blocked fMRI paradigm, we investigated the pattern of neural activation in
      anticipation of a sensory stimulus and during the processing of the somatosensory
      stimulus itself. Tickling was chosen as the somatosensory stimulus rather than
      simple touch in order to increase the probability to get a high degree of
      anticipation. The location and nature of the stimulus were well defined to the
      subject. The state of anticipation was initiated by attributing an uncertainty
      regarding the time of stimulus onset. The network of activation and deactivation
      during anticipation of the expected stimulus was similar to that engaged during
      the actual sensory stimulation. The areas that were activated during both states
      included the contralateral primary sensory cortex, bilateral areas in the
      inferior parietal lobules, the putative area SII, the right anterior cingulate
      cortex and areas in the right prefrontal cortex. Similarly, common decreases were
      observed in areas of sensorimotor cortex located outside the area representing
      the target of stimulus, i.e., areas that process information which is irrelevant
      to the attended process. The overlapping pattern of change, during the
      somatosensory stimulation and the anticipation, furthers the idea that
      predictions are subserved by a neuronal network similar to that which subserves
      the processing of actual sensory input. Moreover, this study indicates that
      activation of primary somatosensory cortex can be obtained without intra-modal
      sensory input. These findings suggest that anticipation may invoke a tonic top
      down regulation of neural activity.

PMID- 10936921
TI  - Meeting report: transcranial magnetic stimulation and studies of human cognition.
AB  - A James S. McDonnell Foundation workshop examined the role of TMS in studies of
      human cognition. A summary of the workshop presentations, discussion, and the
      recommendations appear below. A selected reference list is provided at the end of
      the summary.

PMID- 10936923
TI  - [Gastrointestinal diseases in the elderly].

PMID- 10936924
TI  - [Endothelial dysfunction by oxidized LDL].

PMID- 10936925
TI  - [Factors influencing noncompliance with medication regimens in the elderly].
AB  - Poor medication compliance is a major issue in the health care of older patients.
      To identify risk factors for medication noncompliance in the elderly, inpatients
      aged 65 years and older at Nagoya University Hospital and at Chubu National
      Hospital underwent a comprehensive geriatric assessment and tests for the
      assessment of medication compliance. The dependency of medication assistance by a
      caregiver is associated with low physical function activity, cognitive
      impairment, depression and communication inability. Medication noncompliance was
      not associated with the score of any component of comprehensive geriatric
      assessment. There was a good relationship between patient's knowledge of
      medications and the frequency of dosage interval, both of which were associated
      with the score of instrumental ADL, cognitive function and communication ability.
      The knowledge was also associated with the medication compliance at Nagoya
      University Hospital but not at Chubu National Hospital. These results may suggest
      that the elderly patient's understanding of a medication regimen is important but
      that other factors are also required to maintain their treatment regimen.

PMID- 10936926
TI  - [Agreement between reports by the aged themselves and by their family members on
      physical and psychological status].
AB  - We examined the agreement between reports about physical and psychological status
      obtained from 286 community-dwelling elderly persons aged 65 years and over
      (subjects) and their family members (proxies). A total of 205 subject-proxy pairs
      were studied. Information from subjects was obtained by a self-administered
      questionnaire, and proxy respondents by an interview-administered questionnaire
      between Nov. 1997, and Feb 1998. Agreement was assessed by percent agreement and
      statistical kappa values. Percent agreement ranged from a low of 50.8 for anxiety
      to a high of 90.4 for difficult in swallowing. Kappa values ranged from a low of
      0.21 for anxiety to a high of 0.67 for high frequency of falling. Median kappa
      values were higher in summary measure of physical status (0.52) than in that of
      psychological status (0.39). Compared to subjects, their partners tended to
      report higher level both in physical status and in psychological status, except
      for sleep compliance and introversion. The median kappa was 0.54 for spouses,
      whereas it was 0.39 for family members other than spouses. Overall, our finding
      indicated that partners could be aware of the concrete and directly-observable
      variables of physical status such as constipation, difficult in swallowing, but
      not so for subjective variables as psychological status such as depressed
      condition and introversion. Our results also suggested that the degree of
      agreement of proxy's perception and understanding of lifestyle of the elderly is
      closely related to health status of the elderly.

PMID- 10936927
TI  - [Sleep apnea syndrome and hypertension using desaturation index].
AB  - To examine the roles of obstructive apnea (OA) and central apnea (CA) in oxygen
      desaturation on hypertension and sleep apnea syndrome (SAS), we performed a sleep
      study on 41 elderly subjects (mean age 69.5 +/- 6.8 years, male:female = 31:10).
      Nocturnal oxygen desaturation was documented with a pulse oximeter and apneas (OA
      and CA) were diagnosed on the basis of results of respiratory inductive
      plethysmography and oronasal flow. Significant desaturation (SDS, greater than 5%
      drop in SpO2 from baseline value) and desaturation index (DI; epsilon SDS (%) x
      duration (hour)) were calculated using the continuous nocturnal monitoring system
      with a pulse oximeter. We defined central type apnea above 50% as the central
      type group (n = 8, mean age 58.6 +/- 2.9, mean BMI 21.3 +/- 1.0, male:female =
      7:1), and obstructive type and mixed type apnea above 50% as the obstructive type
      group (n = 21, mean age 70.0 +/- 3.2, mean BMI 25.3 +/- 1.0, male:female = 17:4).
      Other subjects were assigned to the control group (n = 12, mean age 64.3 +/- 2.3,
      mean BMI 23.8 +/- 1.2, male:female = 7:5). The DI (delta 5%) of the central type
      was 0.34 +/- 0.17, and that of the obstructive type was 1.78 +/- 0.7 showing a
      significant increase in the latter compared to the control group (p < 0.02). The
      DI (< 90%) of the central type was 0.14 +/- 0.07, and that of the obstructive
      type was 1.72 +/- 0.75, and that of the obstructive type was significantly
      greater than in the control group (p < 0.05) and central type (p < 0.05). There
      were 4 cases (33.3%) with hypertension in the control group and 4 cases (50.0%)
      with hypertension in the central type group, but there were 15 cases (71.4%) with
      hypertension in the obstructive type group. Hypertensive prevalence in the
      obstructive group was significantly more than in the control group (p < 0.05). No
      significant difference in body mass index or age were seen in the obstructive
      group and control group. There was a significant correlation between mean blood
      pressure and apnea index (AI). The AI of the hypertensive group was significantly
      higher than that of the normotensive group (p < 0.001). These results suggest
      that subjects with significant obstructive apneas may be at greater risk for
      hypertension than subjects with central apneas and that hypertension in the
      pathogenesis of SAS may be related to the severity of apneas rather than
      oxyhemoglobin desaturation.

PMID- 10936928
TI  - [The influence of dietary restriction on the process of age-related disorders in
      male Donryu rats].
AB  - Life span, which is mainly influenced by pathologic lesions, was compared between
      specific pathogen-free male Donryu rats fed ad libitum (AL group) and those with
      dietary restriction (DR group, restricted to 60% of the ad libitum intake). The
      major age-related lesions observed were pituitary tumor, chronic nephropathy,
      cardiomyopathy, and myopathy (anterior tibial and masseter muscle). Dietary
      restriction was effective in slowing the progression of pituitary tumor, chronic
      nephropathy and myopathy in anterior tibial muscle. Although cardiomyopathy
      worsened with age, no difference was seen between the AL and DR group. In
      conclusion, 1) dietary restriction acts to suppress or delay the development of
      pathologic lesions that occur with age, 2) the onset phase of a pathologic lesion
      differs with the lesion and organ involved, 3) inhibiting the development of
      pituitary adenoma and chronic nephropathy can help prolong the life span of rats,
      4) for muscle lesions, depending on their anatomical location, the physiological
      condition of exercise, as well as the relationship with other organs can be
      involved.

PMID- 10936929
TI  - [Age-related clinical features in ischemic colitis].
AB  - Ischemic colitis has been considered to have relatively high prevalence in the
      elderly population with underlying vascular disorder such as hypertension.
      However, this disease has been recently reported increased in the young
      population so that it is not necessarily limited to the aged. The aim of the
      present study was to elucidate the characteristics of age-related clinical
      features in ischemic colitis. The subjects consisted of 30 patients with ischemic
      colitis admitted to our hospital during the last 5 years. They were divided into
      the aged group more than 65 years old and the young group aged 65 or less. As a
      result, there were no significant differences in symptoms, resulted serological
      examination, endoscopic findings, and treatment period. Lesion sites were more
      extended in the aged group. Concerning underlying disease and etiologic factors,
      the vascular factor was important in the aged group, while the peristaltic
      factor, especially constipation was important in the young group. Ten of the 30
      patients had habitual constipation, and the aged group had a high percentage of
      paralytic constipation, while the young group had a high rate of spastic
      constipation. Many patients with paralytic constipation had a history of
      underlying diseases and laparotomy, while the patients with spastic constipation
      did not have such a history. Therefore, it is presumed that the spastic type of
      constipation is an etiologic factor in ischemic colitis.

PMID- 10936930
TI  - [Determinants of endothelial cell damage in the elderly hypertension: assessment
      by plasma von Willebrand factor].
AB  - To investigate the determinants of endothelial cell damage in hypertensive
      elderly patients, we measured the plasma von Willebrand factor (vWF) levels by a
      recently developed enzyme-linked immunosorbent assay using monoclonal antibody
      for the functional epitope. Plasma vWF level was markedly increased in the
      elderly normotensive subjects (n = 42) than in younger normotensive subjects (n =
      39) (127 vs 88%, p < .0001), and was further increased in elderly hypertensive
      subjects (n = 68) (148%, p < .05 vs elderly normotensives). The vWF level was
      positively correlated with body mass index in younger normotensive subjects (r =
      0.41, p < .01), with systolic blood pressure (BP) in elderly normotensive
      subjects (r = 0.41, p < .01), and with age (r = 0.44, p < .001) and fibrinogen
      level (r = 0.37, p < .01) in elderly hypertensive subjects. In elderly
      hypertensive subjects (n = 150), vWF level had a stronger positive correlation
      with 24-hr systolic BP measured (r = 0.41, p < .0001) by ambulatory BP monitoring
      than with clinic systolic BP (r = 0.33, p < .0001). In conclusion, in
      hypertensive elderly patients, endothelial cell damage increases with systolic BP
      and fibrinogen levels, indicating a prethrombotic condition.

PMID- 10936931
TI  - [Rehabilitation of anoxic brain injured patients after reanimation].
AB  - Authors report rehabilitation outcomes of anoxic brain injured patients,
      following reanimation. In the past 12 years (1988-1999) they treated 54 patients.
      The patients were selected from other hospitals after successful reanimation, but
      sustained diffuse anoxic brain injury. The CT and MR examination was generally
      negative, but small hypodensities were shown rarely (18/54). At the time of
      admission 21 patients were quadriparetic, 5 patients were hemiparetic, 2 were
      paraparetic and there were no any paresis in 26 cases. The mean age of the
      patients was 32 years (7-61). At the time of admission 31 patients were dependent
      in basic activities of daily living, the mean Barthel Index score was 15 (0-100)
      but at the time of discharge it was 45 (0-100). 41 patients were discharged into
      their home and 13 patients had to be transmitted to another hospital for further
      treating, but later 5 of them died. At the time of discharge only 7 patients had
      score 100 of the Barthel Index, but they were not able for independent living.
      Family support, mainly guidance was necessary. Memory deficits, apraxia,
      attention disturbance, ataxia were the main problems during the rehabilitation
      process.

PMID- 10936932
TI  - [Affective disorders in a district of Budapest].
AB  - After thorough preparatory work, the authors examined the incidence of affective
      disorders in a representative sample amounting to 1.2% of the population (750
      inhabitants) of the XXI. district of Budapest. The presents study is the second
      one in Hungary to apply the Diagnostic Interview Schedule (DIS), a popular method
      frequently used in the international literature, supplementing this with socio
      demographic data and the Beck Depression Inventory (BDI). Their survey showed a
      low level of religiosity in the sample and a high level of drinking even by self
      admission. Patients with major depression (MD) and dysthymia proved to be at
      almost exactly the same risk of suicide. A high percentage of those suffering MD
      and bipolar disorder sought medical help. The point and lifetime prevalence were
      the following: MD 3.7% and 10.9%, dysthymia 2.9% and 5.3, bipolar disorders zero
      and 1.07%. Their data closely match the values found in the literature. The
      values measured by the DIS are very close to those of full version of BDI, a
      finding which confirms that the full version of BDI is very reliable indicator of
      major depressive states.

PMID- 10936933
TI  - [Comparison of patterns of drug therapy in Hungary and in developed Western
      countries for acute coronary syndromes].
AB  - Analysis of the data of international multicentric clinical pharmacology trials
      disclosed that the Hungarian (and Eastern European) patients are more sick, than
      their western counterparts. The drug prescription habits in Hungary are close to
      that of international standards. The Hungarian doctors order more nitrates,
      anticoagulants and ACE inhibitors, but less cholesterol-lowering medication than
      in other countries. The door-to-needle time in Hungarian patients scheduled for
      thrombolysis was shorter than the mean. The high price of certain thrombolytic
      medications prevents Hungarian hospital's doctors to use optimal thrombolytic
      therapy. The high price of statins in Hungary relative to that of other
      medications for secondary prevention and to the average per capita income is one
      of the possible causes that this class of medication is used less frequently in
      Hungary than in Western Europe. This fact may prevent the decrease of
      cardiovascular morbidity and mortality on the long-term.

PMID- 10936934
TI  - [Regression of gastric MALT lymphoma after eradication of Helicobacter pylori
      infection followed by endoscopic ultrasound].
AB  - The authors report a case of a 42 year-old female patient, who was admitted with
      epigastric pain and weight loss to our department. Upper gastrointestinal
      endoscopy two ulcerated lesions revealed in the stomach at the corpus-antrum
      border. Histologically the lesion proved to be a low grade, malignant B cell MALT
      lymphoma. Coexistent Helicobacter pylori infection was detected with modified
      Giemsa staining. Endoscopic ultrasonography was performed to determine the depth
      of tumorous infiltration of the gastric wall: the tumor was confined to the
      mucosa and submucosa. No regional lymph node was observed. As a result of
      successful Helicobacter pylori eradication the regression of MALT lymphoma
      occurred. The follow-up examinations showed the regression of the tumour and the
      patient became asymptomatic. A control ultrasonographic examinations demonstrated
      the normal five layers structure of the gastric wall without any alteration. In
      our patient Helicobacter pylori eradication was an effective therapy for gastric
      MALT lymphoma as well. Our results similar as are published in the literature.
      Endoscopic ultrasonography is very useful in the assessment of the tumours
      involvement of the gastric wall. In the proper follow-up examinations of the
      patient endoscopy, histology and endoscopic ultrasound together are the methods
      to apply including Helicobacter pylori control.

PMID- 10936935
TI  - [Dr. Lajos Thanhoffer, scientist of histopathology].

PMID- 10936936
TI  - [Lives of military physicians after the surrender at Vilagos].

PMID- 10936937
TI  - [Professional and ethical challenges in reproductive biology and genetics at the
      beginning of the ne millennium].
AB  - About 15 to 20 percent of couples are infertile. Developments in reproductive
      biology have enabled treatment of these couples by means of assisted
      reproduction. In a broader sense, assisted reproductive technologies involve all
      methods aiming to restore impaired reproductive function. Preimplantation genetic
      testing, a new form of prenatal diagnosis, is a result of convergency in the
      development of assisted reproduction and genetics, and allows couples at risk of
      transferring hereditary diseases to their offspring to diagnose such
      abnormalities as early as immediately before or after conception. This article
      describes technologies of assisted reproduction and preimplantation genetic
      diagnosis, and discusses ethical as well as legal issues in reproductive
      medicine.

PMID- 10936938
TI  - [New method for the intraoperative biochemical monitoring of cerebrospinal fluid
      in surgery of thoracoabdominal aortic aneurysms].
AB  - Paraplegia remains to be one of the most dangerous complications following
      thoracoabdominal aortic surgery with an incidence of 0.5 to 40%. Therefore,
      intraoperative monitoring of spinal cord function is very important when choosing
      the appropriate surgical technique. Early detection of spinal cord injury
      continues to be a crucial problem, moreover, the currently applied
      electrophysiological methods appear to be inaccurate. The aim of the study was to
      detect prospective spinal cord injury intraoperatively by monitoring the
      biochemical parameters of the cerebrospinal fluid (CSF). The authors studied the
      reversible aerobic/anaerobic metabolic changes by monitoring CSF lactate levels,
      moreover S-100 protein and neuron-specific enolase (NSE) concentrations--specific
      for neuroglia and neuronal injury, respectively. One of the important methods to
      prevent paraplegia is the intraoperative CSF drainage, which may improve spinal
      cord perfusion. Between 1996-1998 51 patients underwent reconstructive thoracic
      or thoracoabdominal aortic aneurysm operation. The continuously drained CSF was
      collected in 10 ml fractions during the preparation, whereas during aortic cross
      clamping and de-clamping 10 minute fractions were used. All CSF samples were
      immediately analysed intraoperatively for pH, pCO2, HCO3, potassium and lactate
      levels, S-100 protein and NSE were analysed by immunoluminescence. CSF lactate
      levels increased slightly during aortic clamping and a moderate, but non
      significant increase was found in the hyperemic phase (reperfusion) in patients
      without spinal cord ischemia. Spinal cord injury was detected in 7 cases. These
      patients exhibited a significant CSF-lactate increase (control vs aortic cross
      clamping: 1.9 vs 5.3 mmol/l), moreover CSF-lactate remained elevated throughout
      the whole operation. Paraplegia did not occur, Tarlov 2 paraparesis developed in
      four cases and three patients displayed cerebral damage. Intraoperative CSF-
      especially CSF-lactate--monitoring may help the operating team to detect early
      anaerobic changes of the metabolism the spinal cord.

PMID- 10936939
TI  - [Ultrastructural study of bronchial mucosa in suspicion of ciliary dyskinesia].
AB  - In the ciliary dyskinesia (immotile cilia syndrome) shows the partial or total
      lacking of cilia's elements. The ciliary dyskinesia may be developed congenital
      or acquired. The authors report on the experience with 72 biopsies from bronchial
      mucosa of 68 children, submitted with the question of immotile cilia syndrome. On
      micrographs (M: 64,000x) of the specimens processed by routine electron
      microscopical method the number of outer and inner dynein arm, A and B peripheral
      tubules, central tubules and central sheet were determined to normal 9 + 2
      structure. 50-100 ciliaris per case were examined. Total or partial lacking of
      dynein and non-dynein elements were expressed for the total number of ciliaris
      compartments. Considering any earlier quantitative examination with this
      expression there was ease to characterised the quantitative behaviour of the
      components of ciliaris. Seven Kartagener's syndrome cases was the positive
      control for determined the quantitative differences between the primer and
      secondary ciliary changes. In the primary ciliary defects where the situs
      inversus were presented the total lacking of outer or/and inner dynein arms,
      where the situs inversus were not presented only the total lacking of inner
      dynein arms could be found. In secondary ciliary defects the partial lacking of
      the dynein arms and tubular components were presented. The used method is
      suitable to characterise the primary or secondary ciliary defects of bronchial
      mucosa.

PMID- 10936940
TI  - [Health care systems in Nepal].
AB  - This article is the result of some preliminary journey of two Hungarian
      psychiatrist (one also epileptologist, other also anthropologist) to Nepal. The
      main aim of the research was to elaborate a community based epilepsy health care
      pilot project. It is shown a brief look at the modern and traditional health care
      systems and the severely difficult condition of the general and health
      infrastructure in Nepal. Some recommendations of possible help and intervention
      are offered for foreign (Hungarian) doctors.

PMID- 10936941
TI  - [The military hospital in Buda--its organization and function--until 1950].

PMID- 10936942
TI  - [Organization of public health nurses in Tolna county].

PMID- 10936944
TI  - [Troubled Terminology].

PMID- 10936943
TI  - [Surgical treatment of hydrocephalus, with particular emphasis on the Torkildsen
      operation (ventriculocisternostomia). 1949].

PMID- 10936945
TI  - Diagnosis of rubella infection by detecting specific immunoglobulin M antibodies
      in saliva samples: a clinic-based study in Niteroi, RJ, Brazil.
AB  - This study was designed to investigate whether saliva could be a feasible
      alternative to serum for the diagnosis of recent rubella infection in a clinic
      setting. Forty-five paired blood and saliva samples collected 1 to 29 days after
      onset of illness were tested for specific immunoglobulin (Ig) M by antibody
      capture radioimmunoassay (MACRIA). Rubella IgM was detected in all serum samples
      and in 38 (84.4%) saliva specimens. Forty-six serum and saliva samples from other
      patients with rash diseases were tested by MACRIA for control purposes and two
      saliva specimens were reactive. The saliva test had specificity of 96%. These
      results indicate that salivary IgM detection may be a convenient non-invasive
      alternative to serum for investigation of recent rubella cases, especially for
      disease surveillance and control programmes.

PMID- 10936946
TI  - Hepatic pathology in Capillaria hepatica infected mice.
AB  - Septal fibrosis of the liver regularly develops in rats infected with Capillaria
      hepatica. To find out whether such fibrosis also occurs in mice, 20 animals were
      submitted to infection with either 100 or 300 embryonated eggs and histologically
      examined after several periods of time, from 30 to 110 days afterwards. Results
      showed that mice developed acute, severe, diffuse and focal hepatic lesions that
      were soon modulated to focal areas of fibrosis containing eggs and worm remnants,
      despite the fact that a few worms remained alive, at least up to 110 days after
      inoculation. Areas of perisinusoidal fibrosis appeared in the proximity and
      around focal parasitic lesions, but clear-cut septal fibrosis was not observed.
      Whey septal fibrosis forms in rats, but not in mice during C. hepatica infection,
      only further studies can clarify. Mice seem to show better host/parasite
      relationship than rats in regard to C. hepatica infection.

PMID- 10936947
TI  - [Comparative study between larval surveys and ovitraps to monitor populations of
      Aedes aegypti].
AB  - This study compares two techniques for detecting the presence of Aedes aegypti:
      larval surveys and the oviposition trap. In two areas of the municipality of
      Salvador, Bahia, Brazil were investigated 5,026 households. Larval surveys and
      oviposition traps were used simultaneously in these households. Different
      positivity levels (larvae and/or eggs) were detected between and within the two
      areas. However, only the use of the oviposition trap detected a significant
      statistical difference between the areas (z = 9,520, p < 0.001). Comparison of
      the Breteau, Household and Oviposition Indices reveals greater power of detection
      of positivity in the oviposition trap. There were prevalence ratios of positivity
      for oviposition trap of 3.4 and 2.1 (for areas 1 and 2 respectively) when
      compared with larval surveys. The oviposition trap proved to be an economical and
      operationally viable method, and the most effective in the surveillance of this
      species.

PMID- 10936948
TI  - [Evaluation of parameters for laboratory diagnosis of genital female infection by
      Chlamydia trachomatis].
AB  - In order to evaluate the occurrence of Chlamydia trachomatis, we have examined
      samples of cervical swabs from 189 women (166 of which were symptomatic and the
      remaining 23 were asymptomatic with regard to chlamydial infection. Two specimens
      from the endocervical channel were collected and examined by immunofluorescent
      assay (DIF) and Chlamydia isolation. Detection of IgG and IgA antibodies specific
      to C. trachomatis was also effected by indirect immunofluorescent assay (IIF), in
      a cervical secretion sample. We succeeded in isolating chlamydia in 14 (8.4%)
      symptomatic and 3 (13%) asymptomatic women. The observation that the 152
      symptomatic patients with negative results from chlamydia culture presented
      similar symptoms of disease, indicating that there is no specific symptom for
      genital infection caused by Chlamydia (p > 0.05). All the 13 (76.5%) positive
      endocervical specimens, as determined by cell culture and DIF reaction, presented
      more than 5 epithelial cells in the smears. These cells may represent an
      interference factor to the positivity of cell culture (p < 0.001). Antibodies of
      the IgG and/or IgA classes were detected in 11 (64.7%) out of 17 women with
      positive chlamydia culture, considering as positive the IIF titre of > or = 8.
      Consequently, this method can not be used as an alternative means of diagnosis,
      particularly in the earlier stages of chlamydial genital infections, since the
      presence of the antibodies depends on the phase of the infection and on the
      individual humoral immune response.

PMID- 10936949
TI  - Bone marrow fibrosis (pseudo-myelofibrosis) in human kala-azar.
AB  - Thirty cases of human kala-azar were diagnosed by iliac crest biopsy and
      myeloculture. Histological analysis of 12 patients showed diffuse thickening of
      reticulin fibers. To the best of our knowledge, this is the third report
      describing secondary bone marrow fibrosis (myelofibrosis-like) associated with
      kala-azar. Patients with positive bone marrow fibrosis (pbmf = 12) were compared
      to patients without detectable bone marrow fibrosis (wbmf = 18). There were no
      significant differences in clinical and blood parameters following treatment. All
      patients showed regression of hepatosplenomegaly. Our findings suggest that
      associated bone marrow fibrosis is transient and did not interfere in the
      evolution of treated patients.

PMID- 10936950
TI  - Immunodiagnosis of chronic Chagas' disease using the Tc 46 and Tc 58 antigens.
AB  - The polypeptides of 46 and 58 kDa were recognized in different T. cruzi strains
      (Y, WSL and Colombiana) by serum of all chagasic patients studied. These
      polypeptides were isolated from T. cruzi Y strain and used in ELISA. The
      sensitivity and specificity were 97.6% [CI 95%: 86-100%] and 100% [CI 95%: 89.3
      100%], respectively when Tc 46 was used. When Tc 58 was used the sensitivity and
      specificity were 100% [CI 95%: 89.6-100%] and 90.2% [CI 95%: 75.9-96.8%],
      respectively.

PMID- 10936951
TI  - [Maternal and child intestinal parasitism and breast-feeding].
AB  - From March to May 1991, the prevalence of intestinal parasites was detected in
      208 children under two-year old, from out patients attending the Public Health
      Service in Rio de Janeiro. Maternal parasitic infection was simultaneously
      investigated. Information regarding nurseling's breast-feeding and
      enteroparasites rates was also recorded. The centrifugal-sedimentation was the
      method used for stool analysis. Positivity was observed in 12.7% for children and
      37.3% for women. Ascaris lumbricoides was the most frequently detected parasite
      in children under one-year old (4.3%) and mothers (12.7%). The distribution of
      parasites accordingly to breast-feeding showed a significant statistical
      difference (p < 0.05) among infants. No exclusively suckled child presented
      infection. Children whose mothers were infected showed almost two fold risk of
      infection (1.7). A correlation between enteroparasites and weaned children was
      observed (r = 0.75). We believe that infected mothers can contribute for
      parasitic infection of their kids.

PMID- 10936952
TI  - Therapeutic trial in experimental tegumentary leishmaniasis caused by Leishmania
      (Leishmania) amazonensis. A comparative study between mefloquine and aminosidine.
AB  - One hundred and eighty-two male inbred C57/BL/6 mice were infected with 3 x 10(6)
      Leishmania (Leishmania) amazonensis promastigotes of the MHOM/BR/PH8 strain by
      means of a subcutaneous injection in the right ear. The animals were separated in
      three groups: 1) oral mefloquine hydrochloride treatment (16 mg/kg/day/10 days),
      2) intramuscular aminosidine (Paromomycin) treatment (20 mg/kg/20 days) and 3)
      control. Twenty-six mice of each treated group were sacrificed, one at the end of
      treatment (nine weeks after inoculation), and one six weeks later (fifteen weeks
      after inoculation). Control Group animals were sacrificed at weeks six, nine and
      fifteen after inoculation. There was no significant difference between Group 1
      (mefloquine) and Group 3 (control) subjects. Group 2 animals (aminosidine)
      presented the smallest differences of all, both at the end of the treatment and
      six weeks later. The histopato-logical parameters have shown the following
      findings: a) there was no significant difference between the mefloquine treated
      group and the control group; the group treated with aminosidine showed fewer of
      vacuolated macrophages than the control group, at week 9 (end of treatment). b)
      both at the end of treatment and six weeks later, evaluation of tissue necrosis
      and tissue fibrosis revealed no differences between the treated groups. It was
      found that six weeks after the end of treatment, mice in the control group
      presented significantly more severe degrees of fibrosis than mice in the other
      groups. It can be concluded that mefloquine showed limited therapeutic effect in
      this experimental model, whereas aminosidine had a significant effect.
      Nevertheless, neither of them resulted in cure of the lesions.

PMID- 10936953
TI  - [Comparative study between sodium stibogluconate BP 88 and meglumine antimoniate
      in cutaneous leishmaniasis treatment. II. Biochemical and cardiac toxicity].
AB  - Toxicity of two antimonial pentavalents were evaluated in 111 patients with
      cutaneous leishmaniasis. Forty-seven patients received meglumine antimoniate
      (Group I) and 64 patients, sodium stibogluconate BP 88 (Group II), 20 mg
      Sbv/kg/day for 20 days. Evaluation of aminotransferases, alkaline phosphatase,
      amilase, creatinine, urea, urine analysis and electrocardiogram were performed at
      baseline, on the tenth and twentieth day of treatment. Greater frequency of
      aminotransferase abnormal levels were observed on the tenth and twentieth days in
      group II (p < 0.001) and a greater proportion of amilase abnormal levels at the
      tenth day in the same group (p < 0.001). There was a greater variation of
      aminotransferases, alkaline phosphatase and amilase in the first ten days of
      treatment in group II (p < 0.01). On the twentieth day there was a greater
      variation of aminotransferase levels in group II (p = 0.02 and p = 0.03,
      respectively). Forty-three percent of group I and 54% of group II showed
      electrocardiographic abnormalities (p = 0.30).

PMID- 10936954
TI  - [Diagnosis and treatment of hepatitis B].
AB  - Hepatitis B constitutes a serious public health problem. It has been estimated
      that 350 million people--approximately 5% of the world population--have been
      infected by this virus. Of the people infected, in 90% to 95% of them there will
      be a spontaneous resolution of the disease. In 5% to 10% of the cases, though,
      the infection will persist and a chronic hepatitis will develop that may evolve
      leading, in the end, to liver cirrhosis, liver failure and/or carcinoma of the
      liver. The diagnosis of the different stages of the disease (i.e., acute, chronic
      infection) is performed using modern serologic techniques. Physicians, more
      recently, are having access to a series of laboratory tests which permit them to
      evaluate the viral load, replication of the virus and to testing of the efficacy
      of new anti-viral drugs. For the treatment of chronic hepatitis B new agents have
      been tested and some are being used with different degrees of success, such as,
      alfa-interferon, lamivudine, famciclovir, and adefovir dipivoxil, among others.
      Active immunization, using modern recombinant vaccines, are lately, the most
      important instrument of control of the infection caused by the hepatitis B virus.

PMID- 10936955
TI  - South American rattlesnake bite and soft-tissue infection: report of a case.
AB  - The case of a man bitten by a South American rattlesnake (Crotalus durissus) and
      who developed an abscess at the site of the bite is reported. Abcesses are a rare
      complication of this type of envenoming, possibly due to the lack of a strong
      cytotoxic action of Crotalus durissus venom.

PMID- 10936957
TI  - [Occurrence of snail vectors of schistosomiasis in a dam of the semi-arid region
      of Pernambuco State, Brazil].
AB  - The semi-arid region of Pernambuco state is not an endemic or focal area for
      schistosomiasis. The present work registers the occurrence of Biomphalaria
      straminea in a local dam with favorable chemical-physical characteristics to the
      proliferation of these mollusks. This observation gets the attention for the
      possibility of the introduction of the disease in this semi-arid region due to
      the growing multiplication of these dams.

PMID- 10936956
TI  - [Human accidents with stings from Africanized bees].
AB  - It is report five cases of stings of africanized bees (AB). Four of them were
      victims of multiple stings, varying from 25 to 60, that presented severe
      headache, nauseas and vomits, related to the clinic effect of the toxicity of the
      venom, with good evolution. The other case was victim of a single sting of AB and
      died after probable anaphylaxis.

PMID- 10936958
TI  - [Radiotherapy with fast neutrons as palliative treatment of advanced recurrences
      of previously irradiated head and neck tumors].

PMID- 10936959
TI  - [Peliosis hepatis: problems of differential diagnosis].
AB  - Peliosis hepatis is a syndrome manly known to internists and pathologists. It is
      described as roundish blood cysts up to 1 cm large to the found in the hepatic
      parenchyma and correlated to the hepatic sinusoids. The pathogenesis is still
      unclear. The presumably essential disturbance of the structure of the reticular
      fibres is etiologically associated with anabolic and androgenic steroid therapy.
      Peliosis hepatis is pathognomonic for treatment with contraceptives and for
      severe chronic diseases, as tuberculosis or tumour. Little is known of
      therapeutic methods on the diagnostic of peliosis alterations in the liver. As
      peliosis-type hepatic lesions are apt to involution, it is generally recommended
      just to wait and see, with controlling examinations for imaging diagnostics. A
      case is described where a female patient, aged 42, otherwise healthy, came to see
      the doctor for obscure pain in the upper abdomen. Sonography of the upper abdomen
      indicated multiple lesions. The diagnostic method is described taking into
      account possible malign differential diagnoses or associated malign results which
      finally lead to partial resection of the liver.

PMID- 10936960
TI  - [Monstrous venous hemangioma of the retroperitoneum: problems of diagnosis].
AB  - The venal haemangioma is defined as a benign tumor consisting of veinlike
      vessels. The preoperative diagnosis and its inherent problems are illustrated
      using a coincidentally diagnosed monstrous haemangioma tumor of the
      retroperitonial space in a twenty year old patient. With respect to our patient,
      X-ray, computer tomography and angiography all failed as diagnostic tools. Only
      the use of Doppler sonographic flow signals suggested the presence of a
      haemangioma. The morphology, prognosis and clinical significance of blood vessel
      tumors are multifaceted. The most important differential diagnoses to the venous
      haemangioma are the cavernous and the capilliary haemangioma. The venous
      haemangioma distinguishes itself through the presence of blood vessel walls.
      Haemangiomas are common benign tumors. In the presence of highly developed
      muscular components, there exists a transition to angiomyomas and to leiomyomas.
      Venal haemangiomas are extremely rare in the demonstrated localisation of the
      retroperitoneal space. Here they can grow to monstrous preportions whilst
      remaining undetected. Thus the patient is under the potential danger of bleeding
      to death through trivial injuries. The therapy of choice remains total surgical
      excision. In situations of unclear clinical results with respect to preoperative
      diagnosis especially amongst young adults, one should at least consider the
      possibility of a haemangioma as the root of the problem.

PMID- 10936961
TI  - [Hepatocellular carcinoma in an additional pedunculated liver lobe in the lower
      abdomen: differential diagnosis problems].
AB  - The case described is that of a 36 years old patient with a known tumor in her
      lower abdominal cavity which has been observed to increase in size for the passed
      16 years. Intraoperatively, one observed a very rare finding of an extra liver
      lobe of the left liver lobe and located in the lower abdominal cavity. Located
      within is a multifocal therapeutically treatable hepatocellular cancer.

PMID- 10936962
TI  - [Variant of Klippel-Trenaunay syndrome. A case report].
AB  - Klippel-Trenaunay-Syndrome is a rare congenital vascular malformation with
      cutaneous naevi, varicose veins and limb hypertrophy. We report a patient with a
      variant of this syndrome presenting with extensive varicose veins and
      arteriovenous shunts within the left arm, bony hypotrophy of the left hand,
      mucocutaneous melanin spots in the face and thrombocytopenia. Imaging techniques
      play a major role in making a diagnosis in angiophakomatoses.

PMID- 10936963
TI  - [Why T cells?].

PMID- 10936964
TI  - [Molecular signals that determine the clonal selection of T lymphocytes].

PMID- 10936965
TI  - [The role of lipid rafts in T cell receptor (TCR) signaling].

PMID- 10936966
TI  - [A second target of cyclosporin A and FK506].

PMID- 10936967
TI  - [Advance in the study on the proteasome activator PA28].

PMID- 10936968
TI  - [DNA chip; recent advances and applications in gene expression profiling].

PMID- 10936969
TI  - [Inspiration provided by the living world and design of synthetic materials].

PMID- 10936970
TI  - [Quadrupole mass filter instruments and their application].

PMID- 10936971
TI  - The frequency and etiology of anemia among children 6-16 years of age in the
      southeast region of Turkey.
AB  - The frequency and etiology of anemia were investigated in 2,913 children between
      six and 16 years of age in Sanliurfa, in the southeast region of Turkey. Anemia
      was found in 142 (7.8%) children in the 6-11 years of age group, and in 16 (1.5%)
      in the 12-16 years of age group; in total, in 158 (5.4%) children. Causes were
      iron deficiency in 93 (58.9%) children, beta-thalassemia heterozygosity in 10
      (6.3%) children, chronic disease that causes anemia of inflammation in 30 (19.0%)
      children, and intestinal parasitic infections in 17 (10.8%) children. In eight
      (5.1%) children, the cause of anemia could not be determined. The study's results
      showed that iron deficiency anemia and chronic and parasitic disease are
      important problems in schoolchildren of Sanliurfa, while beta-thalassemia and
      hemoglobinopathies have less importance.

PMID- 10936972
TI  - Alternative diagnostic method for streptococcal pharyngitis: Breese scoring
      system.
AB  - This study was performed to determine the effectiveness of the Breese scoring
      system for the diagnosis of streptococcal pharyngitis with respect to different
      age groups. Two hundred and two children aged three years and younger (Group 1),
      and 514 children over three years old (Group 2) with complaints of acute
      pharyngitis were evaluated by Breese scoring and throat-swab cultures. In Group
      1, no significant difference was detected in Breese scoring between subjects who
      had positive and negative culture for group A beta-hemolytic streptococci
      (GABHS). However, in Group 2 the mean value of the Breese scores was found to be
      higher in subjects who had positive GABHS. The diagnostic value of Breese scoring
      was examined for each group. Its sensitivity, and positive and negative
      predictive values were higher in Group 2 than in Group 1. In conclusion, Breese
      scoring was determined to be helpful in the diagnosis of streptococcal
      pharyngitis in children over three years of age.

PMID- 10936973
TI  - Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients.
AB  - Patients with Group A beta-hemolytic streptococcal infection and articular
      disease, who do not fulfill the modified Jones criteria for diagnosis of acute
      rheumatic fever (ARF), have been classified as having poststreptococcal reactive
      arthritis (PSRA). We reviewed the clinical characteristics, laboratory findings
      and outcome of 15 patients with PSRA. None of these patients had clinical
      evidence of carditis. The pattern of joint involvement was variable and included
      arthritis in five patients and arthralgia in the remaining ten patients. Nine
      patients were treated with salicylates for one to 16 weeks; the others recovered
      spontaneously. Usually, the patients with arthralgia responded promptly to
      salicylates, while the response was poor in patients with arthritis. One patient
      with monoarthritis developed carditis nine months after his first arthritis
      attack. Another patient presenting with monoarthritis later had two additional
      episodes of poststreptococcal reactive arthralgia. It seems there is a wide
      spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also
      at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be
      considered in these patients.

PMID- 10936974
TI  - Clinical trial to evaluate immunogenicity and safety of inactivated hepatitis A
      vaccination starting at 2-month-old children.
AB  - Active immunization with hepatitis A vaccine has been shown to provide long-term
      protection against hepatitis A virus (HAV) infection. However, few data are
      available regarding use of the hepatitis A vaccine in children under two years of
      age. The present study was conducted to test the safety and immunogenicity of
      inactivated hepatitis A vaccine administered to infants, and to evaluate the
      correlation between mother and infant anti-HAV antibodies. A total of sixty
      healthy children, two months of age, were enrolled in this study and immunized
      with 360 EU of inactivated hepatitis A vaccine (Havrix) according to the two,
      four and six months of age schedule. Blood sampling was performed prior to the
      first vaccination and one month after the third vaccination at seven months.
      Venipuncture was also done on mother on admission. The reactogenicity was
      expressed as the percentage of reported local and systemic reactions. The most
      common side effects were erythema on the injection site and fever. Infants with
      passively transferred maternal anti-HAV antibodies had a reduced anti-HAV GMT
      after vaccination. On admission, only one infant and his mother were seronegative
      and seroconversion was only detected in this infant. One month after the third
      dose seven infants (12.3%) were found to be seronegative. The infant without
      passively acquired maternal anti-HAV had the protective levels with a GMT of 3176
      mIU/ml one month following the third dose. There was a significant positive
      correlation between the titers of mother and infant anti-HAV antibodies (n =
      0.96, p < 0.001) on admission. Hepatitis A vaccine showed no immunogenicity in
      infants with presence of maternal antibodies. Hepatitis A vaccine is safe but it
      should be used after the disappearance of maternal antibodies.

PMID- 10936975
TI  - Hodgkin's disease and renal paraneoplastic syndromes in childhood.
AB  - The purpose of this study was to investigate children followed as having both
      Hodgkin's disease (HD) and nephropathy and discuss the factors which might play
      roles in the pathogenesis of this association by reviewing the pertinent
      literature. Our experience among 661 children with HD revealed ten cases (1.5%)
      with nephropathy; eight of these were biopsy proven. Tissue diagnoses were
      amyloidosis (AA type) in four cases, and membranoproliferative glomerulonephritis
      and minimal change glomerulopathy in two cases each. Sex distribution was equal.
      There was a predominance of the mixed cellular (MC) histologic type in our
      patients with HD. Nephropathy was shown to antedate the diagnosis of HD in two
      cases and to herald a relapse in one. In brief, the development of a nephropathy
      in a patient with HD can be considered as a paraneoplastic phenomenon. Renal
      amyloidosis may already be present at the time of diagnosis of HD and must be
      kept in mind as a cause of proteinuria due to preexisting nephropathy. Developing
      renal paraneoplastic syndrome, even in early-staged HD, in children, may be a
      poor prognostic factor.

PMID- 10936976
TI  - Arylsulfatase A pseudodeficiency incidence in Turkey.
AB  - Pseudodeficiency (Pd) in arylsulfatase A (ASA) is a relatively frequent condition
      in healthy individuals. It produces a reduction in enzyme activity similar to
      that found in metachromatic leukodystrophy (MLD). A variable incidence of the Pd
      allele was found in different populations; it was 10-20 times higher than that of
      metachromatic leukodystrophy. Twelve of the 52 unrelated, healthy individuals
      were found to be heterozygous for the ASA Pd allele. In Turkey we estimated the
      incidence of the Pd allele as 11.5 percent. Out of 18 cases with MLD, one patient
      was found homozygous for the Pd allele and the other patient was found
      heterozygous.

PMID- 10936977
TI  - Alimentary tract duplications in children: report of 26 years' experience.
AB  - Duplications of the alimentary tract are one of the rare anomalies of the
      gastrointestinal system. Because of the wide spectrum of the signs and symptoms,
      preoperative diagnosis frequently cannot be made. A close familiarity with
      clinical and surgical characteristics provides appropriate management and
      treatment of duplications. A retrospective clinical study was conducted to
      evaluate clinical and surgical characteristics and the treatment of duplications
      of the alimentary tract. During a 26-year period between 1971 and 1997, 38
      patients with duplications of alimentary tract underwent operation at the
      Hacettepe University Department of Pediatric Surgery. Forty-two duplications in
      38 patients (20 male, 53%; 18 female, 47%) were encountered. Sixty-nine percent
      of the patients were symptomatic under the age of one year, with 24 percent
      presenting with symptoms in the neonatal period. There were one sublingual, nine
      intrathoracic (including 2 thoracoabdominal) and 32 intraabdominal duplications.
      Abdominal mass, abdominal distention, constipation, vomiting and respiratory
      distress were the most frequently encountered signs and symptoms. Plain thoracic
      and abdominal X-rays, ultrasonography, and computed tomography of the chest and
      abdomen were the most commonly used diagnostic radiological methods. Thirty-three
      duplications (79%) were spherical and nine (21%) were tubular. Multiple
      duplications were encountered in two patients (5.3%). Fourteen duplications (33%)
      contained heterotopic mucosa, mostly gastric type. More than one type of
      heterotopic mucosa in the same duplication was encountered in four duplications
      (10%). Additional malformations were encountered in 26 percent of patients. Six
      patients (15.8%) died from unrelated causes. The signs and symptoms vary among
      duplications. Signs and symptoms leading to diagnosis and surgery varied
      according to the age of patient, location of the duplication, type of mucosal
      lining, duration of disease and presence of complication. The ideal surgical
      treatment of duplication is complete excision. However, the other treatment
      options should be well known.

PMID- 10936978
TI  - Intermediate-term follow-up results of pulmonary balloon valvuloplasty in
      children.
AB  - Twenty-two patients (10 boys, 12 girls) with pulmonary valve stenosis whose mean
      age was 6.7 +/- 4.1 years (range 1 to 14 years) at time of the procedure
      underwent balloon dilatation angioplasty. All patients had isolated pulmonary
      valve stenosis with no associated cardiac anomalies, and their pulmonary valvular
      gradients were greater than 50 mmHg. Diagnostic catheterization and balloon
      valvuloplasty were performed during the same procedure. The mean peak systolic
      pressure gradient before balloon dilation of 95.8 +/- 29.5 mmHg (54-163 mmHg) was
      reduced to 30.2 +/- 15.8 mmHg (7-64 mmHg) after balloon dilation (p < 0.001). A
      linear relation was found between the predilation pressure gradient and the
      pressure gradient drop (r = 0,86; SE: 28.94) (y = 0.89x - 12.11). Following a
      successful valvuloplasty, the mean peak systolic pressure in the right ventricle
      decreased from 119.0 +/- 30.4 mmHg (71-184 mmHg) to 55.2 +/- 16.9 mmHg (29-97
      mmHg) (p < 0.001). Continuous wave Doppler was used for follow-up. Pressure
      gradients were estimated in 14 patients between one and 29 months after the
      dilation 120 +/- 7.1 months). The mean follow-up gradient was 19.0 +/- 6.0 mmHg
      (11-32 mmHg). No important complication was noted in the immediate course or
      throughout the follow-up period, but four patients (28.6%) had minimal pulmonary
      insufficiency. In conclusion, these data confirm that balloon dilation in
      valvular pulmonary stenosis is safe and effective, and suggest that stenosis does
      not recur.

PMID- 10936979
TI  - Conversion disorder in children and adolescents: clinical features and
      comorbidity with depressive and anxiety disorders.
AB  - The aim of this study was to determine some of the demographical and clinical
      characteristics of conversion disorder in children and adolescents and to
      ascertain comorbidity with depressive and anxiety disorders. For this purpose 51
      children and adolescents (mean age: 13.2 +/- 1.9, range: 9-16 years) who met DSM
      IV criteria for conversion disorder were compared with a control group. The
      subjects of this study were mostly postpubertal girls, and pseudoseizure was the
      most frequent presentation. Misdiagnoses were frequent among these patients.
      Eight (15.7%) patients received a comorbid diagnosis of major depression and 19
      (37.2%) patients had comorbid anxiety disorders according to DSM-IV diagnostic
      criteria. Significant differences between the two groups on depression and
      anxiety scales supported the clinical findings. It was concluded that clinicians
      should screen every patient with conversion disorder for major depression and
      anxiety disorders for a better outcome.

PMID- 10936980
TI  - Are the stool characteristics of preterm infants affected by infant formulas?
AB  - The aim of this study was to investigate the relationship between the type of
      formula consumed and the stool characteristics and gastrointestinal symptoms of
      preterm infants prospectively. Seventy-five preterm infants weighing < 2000 g in
      our neonatal intensive care unit (NICU) were investigated. Four groups of 15 each
      were fed one of four commercial formula preparations (Prematil, Neonatal, Humana
      0 and S-26) and the fifth group was breast-fed in a prospective, randomized,
      double-blind study. The stool characteristics and gastrointestinal problems were
      recorded daily from the first day till the time they were discharged by the
      nurses of NICU. No significant differences of daily weight gain was observed
      between the groups. No significant difference was observed in daily frequency of
      stool, distention, vomiting and gas passage between the groups during the enteral
      + parenteral and full-enteral nutrition periods. The infants fed by Prematil
      during the enteral + parenteral nutrition period had a higher percentage of hard
      stool occurrence than infants receiving Humana-0 and breast milk. In the full
      enteral nutrition period, infants receiving Prematil had a higher percentage of
      hard stool occurrence than all the other groups, whereas breast-fed infants had a
      lower percentage of hard stool than all the other groups. While the group fed
      with Humana-0 had a higher percentage of green stool occurrence in the enteral +
      parenteral nutrition period, no significant difference was observed in the full
      enteral nutrition period. In the enteral + parenteral nutrition period no
      additional therapy affected stool characteristics or the gastrointestinal system
      except in the case of the infant receiving phototherapy for whom the daily number
      of detections was significantly high. In this study, it was shown that the color
      and consistency of stool in preterm infant differs according to the preterm
      infant formulas, but no differences were observed in the frequency of defecation
      or in gastrointestinal system problems. When the infant formulas were compared
      with breast milk, it was shown that they cause a higher percentage of hard stool
      occurrence. An increased number of formula feedings are necessary to obtain a
      similar daily weight gain, but the color and the frequency of the stool and the
      gastrointestinal system problems were similar for breast-fed and formula-fed
      infants.

PMID- 10936981
TI  - Drug-resistant tuberculosis in Turkish children.
AB  - The purpose of this study was to determine the prevalence of anti-tuberculosis
      drug resistance in children followed at Hacettepe University Ihsan Dogramaci
      Children's Hospital. Sixty cases with tuberculosis for whom susceptibility
      testing was available were searched retrospectively. Teh overall drug resistance
      was 26.7 percent. Resistance to streptomycin (sm) was the most frequent (18.3%),
      followed by isoniazid (6.7%), rifampicin (6.5%), and ethambutol (4.2%). Strain
      resistant to more than one drug was present in two cases (3.3%). In summary,
      excluding SM, both single and multidrug resistance were relatively low in our
      pediatric patients.

PMID- 10936982
TI  - Pulmonary hemosiderosis with juvenile rheumatoid arthritis: a case report.
AB  - Pulmonary hemosiderosis may rarely be associated with juvenile rheumatoid
      arthritis or can develop during the course of the disease. We present a three
      year-old boy with severe iron deficiency anemia (without any pulmonary symptoms)
      and arthralgia at the time of diagnosis. Two years after the initial diagnosis he
      developed pulmonary hemosiderosis and pauciarticular type of juvenile rheumatoid
      arthritis which progressed to seronegative polyarticular juvenile rheumatoid
      arthritis. He responded very well to prednisolone and was maintained well on low
      dose alternate-day prednisolone and naproxen sodium treatment. This is the only
      case of association of these two diseases in our experience in both the Pediatric
      Rheumatology and Pediatric Respiratory Diseases Departments.

PMID- 10936983
TI  - Salmonella septic arthritis in a patient with acute idiopathic thrombocytopenic
      purpura treated with steroid.
AB  - Salmonella has three clinical presentations: self-limiting gastroenteritis, a
      systemic syndrome (enteric or typhoid fever), and bacteremia with focal
      infection. Hematogenous infections can cause focal lesions, but unusual
      manifestations occur more often when predisposing factors such as T cell defect,
      hemolytic disorders (sickle cell disease, malaria) or trauma are present.
      Salmonella tend to invade bones and joints. There is no mention of acute
      idiopathic (immune) thrombocytopenic purpura as a predisposing factor for
      salmonella septic arthritis; however there are reports about the importance of
      platelets for the immune response. Here we present a case of Salmonella
      enteritidis septic arthritis following acute idiopathic (immune) thrombocytopenic
      purpura in a 15-year-old female patient who has been on steroid therapy for the
      last two weeks.

PMID- 10936984
TI  - Asplenia in a patient with Fanconi's anemia-like congenital aplastic anemia.
AB  - Fanconi's anemia (FA) is an autosomal recessive disease manifested by
      pancytopenia resulting from bone marrow failure, variable physical anomalies and
      cancer susceptibility. A seven-year-old girl with Fanconi's anemia-like
      congenital aplastic anemia and concurrent asplenia without the congenital heart
      defects or the abdominal heterotaxia is reported. Asplenia was indicated using
      denatured red cells labelled with 51Cr, abdominal ultrasonography and
      computerized tomography. Immunological studies showed immunoglobulins (IgG, IgA,
      IgM), C3 and C4 levels within normal limits and the percentage of CD3, and C4
      cells and the CD4/CD8 ratio decreased. The patient had not been exposed to
      recurrent pneumococcal infections. We think that isolated asplenia may occur in
      patients with Fanconi's anemia-like congenital aplastic anemia without the
      congenital heart diseases or abdominal heterotaxia.

PMID- 10936985
TI  - Prune-belly syndrome associated with extra-abdominal abnormalities in a 7-year
      old boy.
AB  - Prune-belly syndrome (PBS) is an association of abdominal wall deficiency,
      genitourinary anomalies, and in males, cryptorchidism. Other congenital anomalies
      are associated with PBS, particularly musculoskeletal deformities and
      gastrointestinal tract anomalies. In this report, a seven-year-old boy with PBS
      had mega cisterna magna variant, microcornea, aortic stenosis with bicuspid
      aortic valves, cholelithiasis, and Hirschsprung's disease. Coexistence of these
      abnormalities with PBS supports the concept of PBS being caused by an early
      disturbance of not only mesodermal development but also of the other germ layers.
      There was maternal ingestion of drugs in the 1st month of gestation. All cases
      with PBS should be evaluated thoroughly for extra-abdominal abnormalities
      resulting from disturbances of ectodermal and endodermal development. Even though
      disturbances related to ectodermal and endodermal development may be
      asymptomatic, early diagnosis of the disturbances may help in preventing possible
      future problems.

PMID- 10936987
TI  - A case of primary chylous ascites resolved within 4 months by exclusive breast
      feeding.
AB  - Chylous ascites is a rare disease in infancy. A two-month-old male infant was
      admitted to the Department of Pediatrics with chylous ascites. No cause was found
      throughout the investigation period. The baby recovered spontaneously through
      breast-feeding without any specific treatment and chylous ascites disappeared at
      the age of six months.

PMID- 10936986
TI  - Juvenile rheumatoid arthritis presented with thrombocytopenia.
AB  - Leukopenia and thrombocytopenia are rare findings in systemic onset juvenile
      rheumatoid arthritis (S-JRA), and if present, bone marrow (BM) examination is
      necessary to exclude malignant diseases. We report here a 13.5-year-old boy with
      S-JRA who had severe thrombocytopenia and mild leukopenia, without arthritis, at
      the onset of the disease. BM was hypercellular with increased numbers of myeloid
      precursors and megakaryocytes. After treatment with acetylsalicylic acid,
      leukocyte and platelet counts returned to normal levels, and after two months
      chronic arthritis developed.

PMID- 10936989
TI  - Triplets with growth failure, microcephaly, mental retardation, nail hypoplasia
      and corpus callosum agenesis: is it a variant of Coffin-Siris or a new syndrome?
AB  - We report eight-year-old triplet girls whose clinical features included
      microcephaly, severe mental retardation, hypoplasia of distal phalanges of both
      fifth and second fingers and nail hypoplasia on second fingers, dysmorphic facial
      features, and partial corpus callosum agenesis. During infancy, a Pavlik harness
      was used for congenital hip dislocation, and they had difficulty in feeding. One
      had been operated for patent ductus arteriosus. To our knowledge, this rare
      combination has not been previously reported in triplets whose clinical features
      closely resemble those of Coffin-Siris syndrome. The other diagnostic
      possibilities are also reviewed.

PMID- 10936988
TI  - Successful treatment of reactive hemophagocytic syndrome with cyclosporin A and
      intravenous immunoglobulin.
AB  - Infection-associated hemophagocytic syndrome (IAHS) is a form of the reactive
      hemophagocytic syndrome. IAHS is associated with viral, bacterial, fungal,
      mycobacterial, rickettsial and protozoal infections and with various malignant
      neoplasms. A more accurate designation for this acquired form of the syndrome is
      reactive hemophagocytic syndrome (HS). Reactive HS is characterized by malaise,
      fever, hepatosplenomegaly, lymphadenopathy, cytopenia, hypertriglyceridemia,
      hypofibrinogenemia and hemophagocytosis. Cyclosporin A, VP-16, high-dose
      steroids, and intravenous immunoglobulin (IVIG) have been used in the treatment
      of IAHS. Here, a 10-year-old girl with reactive HS due to possible viral
      infection was treated successfully with cyclosporin A and IVIG. Fever disappeared
      on the third day, complete blood count reached normal levels on the sixth day and
      hepatosplenomegaly disappeared on the ninth day after treatment. We believe
      cyclosporin A and IVIG may be used in the treatment of reactive HS, at least in
      selected patients. Further studies are required to confirm its role as first-line
      therapy for children with IAHS.

PMID- 10936990
TI  - Occurrence of an aortic arch anomaly in two siblings born to a diabetic mother.
AB  - A patient with interruption of aortic arch type A, born to a diabetic mother, is
      described. The patient, a male infant, was the fourth child of a 29-year-old
      mother, and had a sibling with coarctation of the aorta. The mother had been
      treated for insulin-dependent diabetes mellitus for the previous 10 years. The
      infant died on the 3rd day of life after symptoms of cardiogenic shock. To our
      knowledge, interruption of aortic arch type A has not been previously described
      in infants of diabetic mothers. The relevance of the case is discussed and the
      literature reviewed.

PMID- 10936991
TI  - Social issues as public health: promise and peril.

PMID- 10936992
TI  - A "call to arms" for a national reporting system on firearm injuries.

PMID- 10936993
TI  - APHA offers new educational opportunities.

PMID- 10936994
TI  - Toward a better educated public health workforce.

PMID- 10936995
TI  - Medical schools, affirmative action, and the neglected role of social class.
AB  - Medical schools' affirmative action policies traditionally focus on race and give
      relatively little consideration to applicants' socioeconomic status or "social
      class." However, recent challenges to affirmative action have raised the prospect
      of using social class, instead of race, as the basis for preferential admissions
      decisions in an effort to maintain or increase student diversity. This article
      reviews the evidence for class-based affirmative action in medicine and concludes
      that it might be an effective supplement to, rather than a replacement for, race
      based affirmative action. The authors consider the research literature on (1)
      medical students' socioeconomic background, (2) the impact of social class on
      medical treatment and physician-patient communication, and (3) correlations
      between physicians' socioeconomic origins and their service patterns to the
      disadvantaged. They also reference sociological literature on distinctions
      between race and class and Americans' discomfort with "social class."

PMID- 10936996
TI  - Competency development in public health leadership.
AB  - The professional development of public health leaders requires competency-based
      instruction to increase their ability to address complex and changing demands for
      critical services. This article reviews the development of the Leadership
      Competency Framework by the National Public Health Leadership Development Network
      and discusses its significance. After reviewing pertinent literature and existing
      practice-based competency frameworks, network members developed the framework
      through sequential use of workgroup assignments and nominal group process. The
      framework is being used by network members to develop and refine program
      competency lists and content; to compare programs; to develop needs assessments,
      baseline measures, and performance standards; and to evaluate educational
      outcomes. It is a working document, to be continually refined and evaluated to
      ensure its continued relevance to performance in practice. Understanding both the
      applications and the limits of competency frameworks is important in individual,
      program, and organizational assessment. Benefits of using defined competencies in
      designing leadership programs include the integrated and sustained development of
      leadership capacity and the use of technology for increased access and quality
      control.

PMID- 10936997
TI  - Mastering the new public health.
AB  - The dramatic changes in the field of public health are reverberating in schools
      of public health in a number of ways, not the least of which is action by the
      deans of the Association of Schools of Public Health (ASPH) to ensure that
      graduates with master's of public health degrees are competent to meet the
      current challenges of practice. The conceptual framework at the center of this
      activity describes 3 domains--skills, perspectives, and applications--in which
      alumni of schools of public health may be required to demonstrate competency.
      ASPH work in this area is grounded in previous national and professional
      competency definitions and school- and department-specific competency
      development; it is distinct from earlier work, however, because its focus is on
      competency at the master's level across the graduate schools of public health.

PMID- 10936998
TI  - Levels of racism: a theoretic framework and a gardener's tale.
AB  - The author presents a theoretic framework for understanding racism on 3 levels:
      institutionalized, personally mediated, and internalized. This framework is
      useful for raising new hypotheses about the basis of race-associated differences
      in health outcomes, as well as for designing effective interventions to eliminate
      those differences. She then presents an allegory about a gardener with 2 flower
      boxes, rich and poor soil, and red and pink flowers. This allegory illustrates
      the relationship between the 3 levels of racism and may guide our thinking about
      how to intervene to mitigate the impacts of racism on health. It may also serve
      as a tool for starting a national conversation on racism.

PMID- 10936999
TI  - "The history of health in Dayton": a community-academic partnership.
AB  - Academic institutions have always found it a challenge to persuade community
      members to participate in academic research projects. Starting an open dialogue
      is usually the critical first step. To begin this dialogue with community members
      in Dayton, Ohio, in 1999, staff from Wright State University decided to organize
      a community forum, "The History of Health in Dayton." The forum was intended as
      the first project of a new research organization, the Alliance for Research in
      Community Health (ARCH), established with federal funding from the Health
      Resources and Services Administration in 1998. ARCH was created as a bridge
      between the Department of Family Medicine of Wright State University School of
      Medicine and the Center for Healthy Communities, a health advocacy and service
      organization committed to health professions education. ARCH's mission is to
      improve the health of citizens of Dayton through research involving community
      participation. Through ARCH, community members help researchers define
      priorities, resolve ethical issues, refine procedures, and interpret results.
      Guidelines for participatory research, proposed by the National Primary Care
      Research Group in 1998 and adopted by the alliance, emphasize the importance of
      open dialogue among researchers, subjects, academics, and community members. The
      initial response to the forum was enthusiastic, with a majority of community
      residents expressing interest in attending future presentations.

PMID- 10937000
TI  - Effects of traditional classroom and distance continuing education: a theory
      driven evaluation of a vaccine-preventable diseases course.
AB  - OBJECTIVES: This study evaluated the effects of a major federal immunization
      continuing education course, delivered in both traditional classroom and
      satellite broadcast versions, on public health professionals' knowledge,
      agreement, self-efficacy, and adherence in practice to recommendations. METHODS:
      The study used a comparative time series design to determine whether the course
      influenced participants' knowledge, agreement, self-efficacy, and adherence in
      practice to general and polio-specific recommendations as measured immediately
      and 3 months after the course. It also compared the effects of the classroom and
      satellite broadcast versions and used path analysis to show how the outcomes were
      related to one another. RESULTS: Both versions significantly improved knowledge,
      agreement, self-efficacy, and adherence. Knowledge and agreement were significant
      predictors of self-efficacy, which directly predicted adherence. Vaccine
      availability and supportive clinic policies were also important adherence
      predictors. CONCLUSIONS: A well-designed training update can change provider
      knowledge, agreement, self-efficacy, and adherence. Traditional classroom and
      distance training can have comparable effects. The findings support incorporation
      of distance learning in national public health training, if the distance learning
      is used wisely in relation to training needs, goals, and practice contexts.

PMID- 10937001
TI  - The impact of multiple predictors on generalist physicians' care of underserved
      populations.
AB  - OBJECTIVES: This study examined the relative and incremental importance of
      multiple predictors of generalist physicians' care of underserved populations.
      METHODS: Survey results from a 1993 national random sample of 2955 allopathic and
      osteopathic generalist physicians who graduated from medical school in 1983 or
      1984 were analyzed. RESULTS: Four independent predictors of providing care to
      underserved populations were (1) being a member of an underserved ethnic/minority
      group, (2) having participated in the National Health Service Corps, (3) having a
      strong interest in practicing in an underserved area prior to attending medical
      school, and (4) growing up in an underserved area. Eighty-six percent of
      physicians with all 4 predictors were providing substantial care to underserved
      populations, compared with 65% with 3 predictors, 49% with 2 predictors, 34% with
      1 predictor, and 22% with no predictors. Sex, family income when growing up, and
      curricular exposure to underserved populations during medical school were not
      independently related to caring for the underserved. CONCLUSIONS: A small number
      of factors appear to be highly predictive of generalist physicians' care for the
      underserved, and most of these predictive factors can be identified at the time
      of admission to medical school.

PMID- 10937003
TI  - Applying burden of disease methods in developing countries: a case study from
      Pakistan.
AB  - OBJECTIVES: Disability-adjusted life-year (DALY) and healthy life-year (HeaLY)
      are composite indicators of disease burden that combine mortality and morbidity
      into a single measurement. This study examined the application of these methods
      in a developing country to assess the loss of healthy life from prevalent
      conditions and their use in resource-poor national contexts. METHODS: A data set
      for Pakistan was constructed on the basis of 180 sources for population and
      disease parameters. The HeaLY approach was used to generate data on loss of
      healthy life from premature mortality and disability in 1990, categorized by 58
      conditions. RESULTS: Childhood and infectious diseases were responsible for two
      thirds of the burden of disease in Pakistan. Condition-specific analysis revealed
      that chronic diseases and injuries were among the top 10 causes of HeaLY loss.
      Comparison with regional estimates demonstrates consistency of disease trends in
      both communicable and chronic diseases. CONCLUSIONS: The burden of disease in
      countries such as Pakistan can be assessed by using composite indicators. The
      HeaLY method provides an explicit framework for national health information
      assessment. Obtaining disease- and population-based data of good quality is the
      main challenge for any method in the developing world.

PMID- 10937002
TI  - Outcomes of the Learn, Share & Live breast cancer education program for older
      urban women.
AB  - OBJECTIVES: This study assessed whether the Learn, Share & Live breast cancer
      education program resulted in favorable, replicable, and sustainable outcomes.
      METHODS: The program was implemented at index (year 1) and replication (year 2)
      sites. Baseline interviews (year 1; n = 240) and 2 follow-up telephone interviews
      (years 2 and 3; n = 337 and 323) were used to assess postintervention changes.
      RESULTS: From baseline to year 2, mammography adherence and stage of adoption
      improved at the index site relative to the replication site. Knowledge scores and
      percentages of respondents reporting that a friend had spoken with them about
      mammography improved significantly. Improvements were sustained through year 3 (2
      years postintervention). In year 3, replication participants showed improvements
      in regard to knowledge and perceived mammography benefits, and there was a trend
      toward increased adherence. Site differences in postintervention adherence may
      have stemmed from respective choices of follow-up activities. CONCLUSIONS: The
      study outcomes affirm the impact of Learn, Share & Live, indicating a replicated
      and sustained program effect. Future studies should continue longer follow-up and
      explore the importance of providing mammography opportunities along with
      education.

PMID- 10937004
TI  - A national burden of disease calculation: Dutch disability-adjusted life-years.
      Dutch Burden of Disease Group.
AB  - OBJECTIVES: This study estimated the burden of disease due to 48 major causes in
      the Netherlands in 1994 in disability-adjusted life-years (DALYs), using national
      epidemiologic data and disability weights, and explored associated problems and
      uncertainties. METHODS: We combined data from Dutch vital statistics,
      registrations, and surveys with Dutch disability weights to calculate disease
      specific health loss in DALYs, which are the sum of years of life lost (YLLs) and
      years lived with disability (YLDs) weighted for severity. RESULTS: YLLs were
      primarily lost by cardiovascular diseases and cancers, while YLDs were mostly
      lost by mental disorders and a range of chronic somatic disorders (such as
      chronic nonspecific lung disease and diabetes). These 4 diagnostic groups caused
      approximately equal numbers of DALYs. Sensitivity analysis calls for improving
      the accuracy of the epidemiologic data in connection with disability weights,
      especially for mild and frequent diseases. CONCLUSIONS: The DALY approach
      appeared to be feasible at a national Western European level and produced
      interpretable results, comparable to results from the Global Burden of Disease
      Study for the Established Market Economies. Suggestions for improving the
      methodology and its applicability are presented.

PMID- 10937005
TI  - Bias in proxies' reports of disability: data from the National Health Interview
      Survey on disability.
AB  - OBJECTIVES: These studies examined whether differences between self-reports and
      proxy reports of disabilities reflect proxy response biases or only respondent
      selection factors. METHODS: The data were from the National Health Interview
      Survey on Disability (1994-1995, phases 1 and 2). In study 1, reports of
      disabilities were regressed on respondent status, self vs proxy, and demographic
      factors. In study 2, the ratios of the proportions of self-reports and proxy
      reports of disabilities were regressed on independent lay ratings of
      observability of these disabilities and their "interactional" nature. In study 3,
      the disability reports for people who differed in respondent status in one phase
      but self-reported the same disability in the other phase were compared. RESULTS:
      In study 1, proxies under-reported disabilities for people aged 18 to 64 years
      but overreported for people 65 years or older. In study 2, the observability and
      interactional scores accounted for more than 60% of the variance of self and
      proxy differences in an inverse relationship, study 3 confirmed the basic
      findings of study 1. CONCLUSIONS: Use of proxies in representative surveys on
      disability introduces systematic biases, affecting national disability estimates.

PMID- 10937006
TI  - A longitudinal study of drinking and cognitive performance in elderly Japanese
      American men: the Honolulu-Asia Aging Study.
AB  - OBJECTIVES: This study prospectively describes the relationships between alcohol
      intake and subsequent cognitive performance among participants in the Honolulu
      Heart Program (HHP). METHODS: Alcohol intake was assessed at Exam III of the HHP,
      and cognitive performance was measured approximately 18 years later with the
      Cognitive Abilities Screening Instrument (CASI). Complete information was
      available for 3556 participants, aged 71 to 93 years at follow-up. RESULTS: In
      multivariate analyses, the relationship between drinking and later cognitive
      performance appeared nonlinear, as nondrinkers and heavy drinkers (more than 60
      ounces of alcohol per month) had the lowest CASI scores and the highest risks of
      poor and intermediate CASI outcomes. Compared with nondrinkers, the risk of a
      poor CASI score was lowered by 22% to 40% among men who consumed 1-60 ounces of
      alcohol per month. CONCLUSIONS: We report a positive association between moderate
      alcohol intake among middle-aged men and subsequent cognitive performance in
      later life. However, it is possible that the health risks associated with
      drinking outweight any potential benefits for many elderly persons.

PMID- 10937007
TI  - Educational level, relative body weight, and changes in their association over 10
      years: an international perspective from the WHO MONICA Project.
AB  - OBJECTIVES: This study assessed the consistency and magnitude of the association
      between educational level and relative body weight in populations with widely
      different prevalences of over-weight and investigated possible changes in the
      association over 10 years. METHODS: Differences in age-adjusted mean body mass
      index (BMI) between the highest and the lowest tertiles of years of schooling
      were calculated for 26 populations in the initial and final surveys of the World
      Health Organization (WHO) MONICA (Monitoring Trends and Determinants in
      Cardiovascular Disease) Project. The data are derived from random population
      samples, including more than 42,000 men and women aged 35 to 64 years in the
      initial survey (1979-1989) and almost 35,000 in the final survey (1989-1996).
      RESULTS: For women, almost all populations showed a statistically significant
      inverse association between educational level and BMI; the difference between the
      highest and the lowest educational tertiles ranged from -3.3 to 0.4 kg/m2. For
      men, the difference ranged from -1.5 to 2.2 kg/m2. In about two thirds of the
      populations, the differences in BMI between the educational levels increased over
      the 10-year period. CONCLUSION: Lower education was associated with higher BMI in
      about half of the male and in almost all of the female populations, and the
      differences in relative body weight between educational levels increased over the
      study period. Thus, socioeconomic inequality in health consequences of obesity
      may increase in many countries.

PMID- 10937008
TI  - Agricultural work-related injuries among farmers in Hubei, People's Republic of
      China.
AB  - OBJECTIVES: This population-based study evaluated patterns of and risk factors
      for, agricultural injuries among farmers in the People's Republic of China.
      METHODS: A multistage sample of 1500 Chinese farmers was selected from 14
      villages. Face-to-face interviews with 1358 farmers were conducted between July
      1997 and September 1997 (response rate = 91%). Agricultural work-related injuries
      that occurred in the previous 24 months and the associated factors were
      evaluated. RESULTS: A total of 33% of the farmers reported at least 1 work
      related injury in the 24 months before the survey. Major external causes of the
      injuries were hand tools (50%), falls (26%), and heavy falling objects (10%). The
      statistically significant risk factors for injury were low family income, 1 to 6
      school years of education, self-reported pesticide exposure, tension in
      relationships with neighbors, and stress in life. The most notable result was the
      relation between self-reported pesticide exposure and injury, with farmers with
      greater pesticide exposure at significantly greater risk for injury. CONCLUSIONS:
      The results of this study indicated that injuries occurring among Chinese farmers
      may have unique patterns and potential risk factors.

PMID- 10937010
TI  - Opinion leaders' support for tobacco control policies and participation in
      tobacco control activities.
AB  - OBJECTIVES: Because opinion leaders hold positions from which they may influence
      tobacco control efforts, this study examined their support for tobacco control
      policies and their involvement in tobacco control activities. METHODS: A
      telephone survey was administered to 712 California opinion leaders who were
      randomly selected from constructed lists representing 8 types of organizations:
      health, education, law enforcement, media, government, business, ethnic, and
      youth. Hierarchical regression analysis was used to identify predictors of
      support for and participation in tobacco control activities. RESULTS:
      Approximately one half to two thirds of opinion leaders supported the tobacco
      control policies queried; 60% reported involvement in tobacco control-related
      activities during the previous year. Organizational affiliation was a strong
      predictor of support and involvement, with leaders from health and educational
      organizations reporting the highest levels and business and media leaders
      reporting the lowest. Tobacco issue involvement variables (e.g., having a friend
      or family member with a smoking-related illness) were significantly associated
      with the outcomes, while sociodemographics, for the most part, were not.
      CONCLUSIONS: Study results can be used to mobilize opinion leaders' support for
      tobacco control more effectively.

PMID- 10937009
TI  - Socioeconomic status and multiple myeloma among US blacks and whites.
AB  - OBJECTIVES: This study examined the relation between socioeconomic status (SES)
      and risk of multiple myeloma among Blacks and Whites in the United States.
      METHODS: This population-based case-control study included 573 cases (206 Blacks
      and 367 Whites) with new diagnoses of multiple myeloma identified between August
      1, 1986, and April 30, 1989, and 2131 controls (967 Blacks and 1164 Whites) from
      3 US geographic areas. Information on occupation, income, and education was
      obtained by personal interview. RESULTS: Inverse gradients in risk were
      associated with occupation-based SES, income, and education. Risks were
      significantly elevated for subjects in the lowest categories of occupation-based
      SES (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.16, 2.53),
      education (OR = 1.36, 95% CI = 1.06, 1.75), and income (OR = 1.43, 95% CI = 1.05,
      1.93). Occupation-based low SES accounted for 37% of multiple myeloma in Blacks
      and 17% in Whites, as well as 49% of the excess incidence in Blacks. Low
      education and low income accounted for 17% and 28% of the excess incidence in
      Blacks, respectively. CONCLUSIONS: Our results indicate that the measured SES
      related factors account for a substantial amount of the Black-White differential
      in multiple myeloma incidence.

PMID- 10937012
TI  - Needs assessment and a model agenda for training the public health workforce.
AB  - OBJECTIVES: A training needs assessment project tested the use of "universal"
      competencies for establishing a model training agenda for the public health
      workforce. METHODS: Agency supervisors selected competencies for training
      priorities. Regional and national public health leaders used these selections to
      design the model training agenda. RESULTS: The competencies given high priority
      by supervisors varied among state and local agencies and included some not within
      the universal set. The model training agenda reflected supervisors' priorities as
      well as leaders' perspectives. CONCLUSIONS: The universal competencies provide a
      useful starting point, but not necessarily an exclusive framework, for assessing
      and meeting the training needs of the public health workforce.

PMID- 10937011
TI  - Type 2 diabetes is prevalent and poorly controlled among Hispanic elders of
      Caribbean origin.
AB  - OBJECTIVES: We estimated prevalence and control of type 2 diabetes in Puerto
      Rican, Dominican, and non-Hispanic White (NHW) elders and associated them with
      sociodemographic and health behavior variables and with body mass index (BMI) and
      waist circumference. METHODS: We used a cross-sectional analysis with a sample of
      Hispanic elders in Massachusetts and a comparison group of NHWs (1991-1997). The
      analysis included 379 Puerto Ricans, 113 Dominicans, and 164 NHWs, aged 60 to 96
      years, with complete questionnaires and blood samples. RESULTS: Type 2 diabetes
      was significantly more prevalent among Puerto Ricans (38%) and Dominicans (35%)
      than among NHWs (23%). Differences remained after covariates were adjusted for.
      Hispanics with diabetes were approximately 3 times more likely to use insulin
      than NHWs. Puerto Ricans were 2 times, and Dominicans 3 times, more likely to
      have glycosylated hemoglobin concentrations of 7% or above than NHWs. BMI and
      waist circumference were individually associated with diabetes. When included in
      the model together, waist circumference, but not BMI, remained independently
      associated with diabetes. CONCLUSIONS: Ethnicity was more strongly associated
      with diabetes status and control than were socioeconomic or measured health
      behavior variables, suggesting that genetic or other culturally related factors
      may explain these differences.

PMID- 10937014
TI  - Public requests for cancer cluster investigations: a survey of state health
      departments.
AB  - OBJECTIVES: This study examined the frequency of requests that state health
      departments investigate cancer clusters, the nature of those requests, and the
      resources available for the investigations. METHODS: A mail survey was sent to
      state health departments requesting data for 1997. RESULTS: Approximately 1100
      cluster investigation requests were made in 1997. Most requests were made by
      citizens, and no pattern emerged for types of cancer or hazards suspected. States
      rate this work as average in importance and feel satisfied with the
      successfullness of their communication efforts. CONCLUSIONS: Few cluster
      inquiries require further investigation. Nonetheless, this interaction represents
      resources well spent in terms of public service and education.

PMID- 10937013
TI  - Reliability and validity of disability questions for US Census 2000.
AB  - OBJECTIVES: We investigated the validity and proxy reliability of 7 new
      disability questions from the 2000 US census ("Census 2000"). METHODS: A total of
      131 people with disabilities and their proxies from St Louis, Mo, and
      Massachusetts were interviewed, and responses were compared for concordance.
      Responses also were compared with responses to questions from the Behavioral Risk
      Factor Surveillance System (BRFSS) and the Activities of Daily Living (ADL)
      instrument. RESULTS: Overall, proxies reported more impairment than did people
      with disabilities, and agreement was low (kappa = 0.24-0.55). Concordance was
      moderate between the census questions and their BRFSS and ADL counterparts.
      CONCLUSIONS: The Census 2000 questions may not provide an accurate profile of
      disability in America.

PMID- 10937015
TI  - Effect of nonviable infants on the infant mortality rate in Philadelphia, 1992.
AB  - OBJECTIVES: This report measured the effect of births at 22 weeks' gestation or
      earlier on infant mortality in Philadelphia, Pa. METHODS: The proportion of live
      born deliveries at 22 weeks or earlier was calculated. Overall and race-specific
      infant mortality was calculated after excluding live-born deliveries at 22 weeks'
      gestation or earlier. RESULTS: Of all deliveries, 1.5% were at 22 weeks or
      earlier. Of these, 68% were stillborn and 32% were live-born. Large hospital-to
      hospital variation in the proportion of live-born deliveries at 22 weeks'
      gestation or earlier was noted. When nonviable births were excluded, overall
      infant mortality decreased 40%. CONCLUSIONS: The development of a standardized
      birth certificate policy is needed and will facilitate comparisons of infant
      mortality across spatial boundaries and racial/ethnic groups.

PMID- 10937016
TI  - Predictors of cigarette smoking and smoking cessation among adults with asthma.
AB  - OBJECTIVES: This study sought to determine the predictors of smoking and time
      until smoking cessation in a cohort of adults with asthma. METHODS: Adults with
      asthma (n = 374) in northern California completed structured telephone interviews
      at baseline and 18-month follow-up. RESULTS: Of the 374 subjects, 156 reported
      ever having smoked, and 39 indicated that they currently smoked. Earlier birth
      cohort, lower educational attainment. White race, and presence in childhood
      residence of an adult who smoked were associated with a greater risk of ever
      smoking. Lower educational attainment, early smoking initiation, higher daily
      cigarette consumption, and late-childhood-onset asthma were associated with a
      longer interval until smoking cessation. CONCLUSIONS: Persons with asthma at high
      risk of cigarette smoking and delayed quitting can be identified on the basis of
      clinical and demographic characteristics.

PMID- 10937017
TI  - A simulation of the effects of youth initiation policies on overall cigarette
      use.
AB  - OBJECTIVES: We developed a simulation model to predict the effects of policies
      aimed at reducing smoking initiation by youths younger than 18 years. METHODS:
      The model projected the number of smokers, never smokers, and ex-smokers by age,
      sex, and racial/ethnic group and the effects of reductions in youth initiation.
      RESULTS: The model predicted that even if tobacco policies eliminated youth
      initiation, the number of smokers would not be halved for more than 30 years. If
      initiation were halved and some of the initiation were delayed rather than
      eliminated, substantially smaller reductions would result. CONCLUSIONS: Policies
      that increase cessation rates are needed to reduce the number of current smokers
      and the more near-term health problems.

PMID- 10937018
TI  - Disability and the curriculum in US graduate schools of public health.

PMID- 10937020
TI  - Public health E-mentoring: an investment for the next millennium.

PMID- 10937019
TI  - The health-damaging potential of new types of flexible employment: a challenge
      for public health researchers.

PMID- 10937021
TI  - Measuring smokers' perceptions of the health risks from smoking light cigarettes.

PMID- 10937022
TI  - Civilian protection measures against terrorist attack are the best preventive
      medicine.

PMID- 10937023
TI  - Anthrax vaccination is based on medical evidence.

PMID- 10937024
TI  - Bioterrorism initiatives: public health support.

PMID- 10937025
TI  - Australian general practice: the need for leaders and vision.

PMID- 10937026
TI  - Diagnosing Australians at risk of diabetes mellitus in general practice.

PMID- 10937027
TI  - The BEACH study of general practice.

PMID- 10937028
TI  - General practitioners and public health.

PMID- 10937029
TI  - Public health and preventive healthcare in children: current practices of
      Victorian GPs and barriers to participation.
AB  - OBJECTIVES: To assess general practitioners' attitudes to and involvement in
      child public health activities and identify barriers affecting their
      participation. DESIGN: Cross-sectional written questionnaire survey of a
      representative sample of actively practising GPs. SETTING: General practices in
      the State of Victoria. PARTICIPANTS: 840 GPs returned questionnaires (65%
      response rate), and, of these, 792 (94%) saw children 0-12 years. MAIN OUTCOME
      MEASURES: Attitudes to and involvement in public health promotion; predictive
      factors for GPs' involvement. RESULTS: The odds of GPs' involvement in child
      public health issues were increased by being female (odds ratio [OR], 1.88),
      receiving basic medical qualifications outside Australia (OR, 1.55), attending
      continuing education and postgraduate training (OR, 1.60), and having confidence
      in dealing with newborns and infants (OR, 1.93) and preschool children (OR, 2.94)
      (both P < 0.05). Older GPs, compared with younger GPs, had significantly lower
      odds of involvement (P < 0.01). After adjustment, GPs had higher odds of
      involvement if they agreed it was important for them to take part in health
      promotion, or in screening and surveillance (OR, 2.76 and 1.94, respectively; P <
      or = 0.05); and lower odds if they agreed that screening and surveillance should
      be mainly done by maternal and child health nurses (OR, 0.60). The most common
      barriers to involvement were insufficient time, inadequate financial
      reimbursement for long consultations, inappropriateness of raising these issues
      in children presenting with illness, and lack of community resources.
      CONCLUSIONS: Increasing GPs' involvement in child public health will require
      attention to barriers (time, remuneration and perceived appropriateness),
      continuing education and changes in workforce composition and patterns.

PMID- 10937030
TI  - Adult vaccination: old needs, new challenges and opportunities.

PMID- 10937031
TI  - Survey of pertussis morbidity in adults in western Sydney.
AB  - OBJECTIVE: To estimate morbidity due to Bordetella pertussis infection in a
      representative population of Australian adults. DESIGN: Telephone survey using
      structured questionnaire. PARTICIPANTS: Adults (aged 20 years and over) notified
      with pertussis to a public health unit in western Sydney between 1 December 1997
      and 31 May 1998. MAIN OUTCOME MEASURES: Duration of cough; time to improvement;
      symptoms and complications; time to diagnosis; health resource use; lost work
      days. RESULTS: Of 90 eligible patients, 73 (81%) completed questionnaires. Cough
      lasted a median of 60 days, but persisted over 90 days in 20 people (27%).
      Presentation was within a median of seven days of symptom onset, but diagnosis of
      pertussis took a median of 21 days. Participants reported a mean of 3.7 general
      practitioner visits and 1.2 prescription drugs. Of those employed, 17 (35%)
      missed more than five work days (range, 0-93 days). CONCLUSIONS: B. pertussis
      infection in adults can result in prolonged, significant disruption to social and
      working life. Results suggest that, in 1998, there were more than 8000 general
      practitioner visits and 15,000 lost work days caused by pertussis in Australian
      adults.

PMID- 10937033
TI  - What role for Divisions of General Practice in addressing health inequity within
      their communities?

PMID- 10937032
TI  - Healthcare for older people in residential care--who cares?

PMID- 10937034
TI  - The mental health of older people in the community.

PMID- 10937035
TI  - Carotid sinus massage in the elderly: is it worth the risk?

PMID- 10937036
TI  - Physical activity and cardiovascular risk factors: effect of advice from an
      exercise specialist in Australian general practice.
AB  - OBJECTIVE: To determine whether provision of individualised physical activity
      advice by an exercise specialist in general practice is effective in modifying
      physical activity and cardiovascular risk factors in older adults. DESIGN:
      Randomised controlled trial of individualised physical activity advice,
      reinforced at three and six months (intervention) versus no advice (control).
      SETTING: Two general practices in Adelaide, South Australia, 1996. PARTICIPANTS:
      299 adults aged 60 years or more who were healthy, sedentary and living in the
      community. MAIN OUTCOME MEASURES: Changes to physical activity (frequency and
      duration of walking and vigorous exercise), selected cardiovascular risk factors
      (blood pressure, body weight, serum lipid levels) and quality of life over 12
      months. RESULTS: Self-reported physical activity increased over the 12 months in
      both groups (P < 0.001). The increase was greater for the intervention than the
      control group for all measures except time spent walking (P < 0.05). More
      intervention than control participants increased their intention to exercise (P <
      0.001). Serum levels of total and low-density lipoprotein cholesterol and
      triglycerides fell significantly over the 12 months to a similar extent in the
      two groups. No other significant changes in cardiovascular risk factors were
      seen. Quality-of-life scores decreased over the 12 months. The decrease was
      significantly greater among intervention than control women, but not men, for
      emotional well-being (P = 0.02), physical well-being (P = 0.04) and social
      functioning (P = 0.04). DISCUSSION: Provision of general practice-based physical
      activity advice reinforced three-monthly produced a sustained increase in self
      reported physical activity. However, there were no associated changes in clinical
      measures of cardiovascular risk factors and minimal changes in quality-of-life
      measures.

PMID- 10937037
TI  - Healthy ageing: what role can physical activity play?

PMID- 10937038
TI  - General practice reform in the United Kingdom: moving into the new millennium.
AB  - Radical reform of general practice is under way in the United Kingdom, driven by
      a National Health Service "modernisation" agenda and the promise of additional
      resources from the Blair Government. Australian GPs can not afford to ignore
      these changes and should ensure that through their representative bodies they
      influence any similar changes in Australia.

PMID- 10937039
TI  - Complementary therapies: the appeal to general practitioners.
AB  - Pragmatism--among consumers seeking a cure and among general practitioners
      seeking clinical results and more patients--is not a complete explanation for the
      burgeoning of complementary and alternative medicine (CAM) in Western societies.
      Instead, this growth is substantially a result of pervasive and rapid social
      change, alternatively termed 'globalisation' and 'postmodernisation'.
      Globalisation and postmodernisation are creating a new social reality, of which a
      prominent characteristic is the proliferation of consumer choice. GPs are
      enmeshed in this social change and subject to the trend to greater choice--both
      their patients' and their own. On the one hand, GPs are reacting to social change
      as "economic pragmatists", responding to consumers' increasing demand for CAM. On
      the other hand, GPs themselves are acting as agents of social change by
      acknowledging the limitations of orthodox biomedical treatments and promoting CAM
      as part of their service delivery. Lack of scientific validation of CAM has not
      prevented GPs' use of such therapies. The phrase "clinical legitimacy" can be
      seen as a trump card that overrides "scientific legitimacy". It is the shibboleth
      of a postmodern movement among GPs towards healing and the "art" of medicine, as
      opposed to the "science" of medicine per se.

PMID- 10937040
TI  - Preliminary experiences with a single-patient trials service in general practice.
AB  - OBJECTIVE: To pilot a single-patient trials (SPTs) service in general practice,
      designed to improve decision-making about long-term medications for chronic
      conditions. DESIGN: 12-week within-patient, randomised, double-blind, placebo
      controlled, crossover comparison of ibuprofen with paracetamol for
      osteoarthritis, involving three pairs of two-week treatment periods for each
      participating patient. SETTING AND PATIENTS: Patients attending an academic
      general practice with a clinical diagnosis of osteoarthritis, with pain of at
      least a month's duration severe enough to warrant consideration of long-term non
      steroidal anti-inflammatory drug (NSAID) use. MAIN OUTCOME MEASURES: Pain and
      stiffness; measures of overall arthritis compared with previous fortnight;
      preference for NSAID at the end of each two-week treatment period; use of escape
      analgesia; side effects; and management changes as a result of the SPTs. RESULTS:
      Eight of 14 patients completed SPTs. One was a clear responder to NSAIDs, five
      were non-responders, and two were indefinite. Of the five who were using NSAIDs'
      before the SPT, two continued and three ceased using them. Clinically useful
      information assisted decision-making for all eight participants. Medication
      management changed for six. CONCLUSIONS: Single-patient trials can be
      successfully implemented in general practice and might be a valuable method for
      GPs to identify patients who respond to medication for chronic stable conditions
      such as osteoarthritis, in which individual response to medication is variable.

PMID- 10937041
TI  - An approach to managing depression in general practice.
AB  - Detection of depression in primary care can be enhanced by use of self-report
      assessment forms. With the new classes of antidepressants, there is the
      opportunity to choose specific drug classes for different types of depressive
      disorders. Depression is frequently a relapsing illness. Treatment goals should
      include long term reduction of vulnerability factors. An active therapeutic
      partnership can be facilitated by providing accurate detailed information early
      in the course of the illness. Behavioural therapies, which focus on modification
      of the sleep-wake cycle, activity planning and reduction of substance abuse, are
      essential. Structured problem solving is the most accessible form of cognitive
      intervention that general practitioners can readily provide. More complex
      cognitive therapies are usually provided by mental health professionals or
      general practitioners with extensive training.

PMID- 10937042
TI  - Classification of small B-cell lymphoid neoplasms using a paraffin section
      immunohistochemical panel.
AB  - Immunophenotypic analysis is critical in categorizing small B-cell neoplasms;
      however, many recommended antibody panels have required fresh or frozen tissue.
      Many paraffin-reactive antibodies are now available but have been studied mostly
      in isolation. Therefore, the utility of a panel of paraffin-reactive antibodies
      in differentiating small B-cell neoplasms was investigated. Paraffin-embedded
      sections of small lymphocytic lymphoma/B-chronic lymphocytic leukemia (SLL/B-CLL;
      12), mantle cell (MCL; 15), follicular (FL; 11), and marginal zone B-cell (MZL;
      eight) lymphomas were stained with CD20/L26, CD3, CD43/DF-T1 or Leu22, CD5/4C7,
      CD23/BU38, cyclin D1/H295, and CD10/56C6 antibodies. For select antibodies,
      results were compared to flow cytometric data (FC). Formalin and B5 fixation were
      also compared. Seven of 11 SLL/B-CLL were CD43+ CD5+ CD23+ cyclin D1- CD10-;
      seven of 11 MCL were CD43+ CD5+ CD23- cyclin D1+ CD10-; nine of 10 FL were CD43-
      CD5- CD23- cyclin D1- CD10+; and five of six MZL were CD43+ CD5- CD23- cyclin D1-
      CD10-. CD5, CD23, and CD10 stains showed sensitivities of 81, 88, and 100%,
      respectively, compared to FC. With B5 fixation, cyclin D1 was more often negative
      and CD5 more often equivocal. A panel of paraffin-reactive antibodies aids in
      classification of small B-cell neoplasms, although a small number of cases have
      indeterminate phenotypes and MZL have no defining features. CD5 separates most
      SLL/B-CLL and MCL from FL and MZL. CD23 separates SLL/B-CLL from most MCL, but
      cyclin D1 is most important for identifying MCL. CD10 positivity distinguishes
      most FL from other small B-cell lymphoid neoplasms.

PMID- 10937043
TI  - BRCA1, C-erbB-2, and H-ras gene expressions in young women with breast cancer. An
      immunohistochemical study.
AB  - Young age does not seem to be directly related to the aggressiveness of the
      disease among patients with breast cancer. Identification and analysis of the
      alterations in a susceptibility gene expression in breast cancer occurring in
      young women may allow identification of those patients in whom tumors will show
      an aggressive clinical course. The purpose of the present study was to evaluate
      the association of BRCA1, H-ras, and c-erbB-2 gene expression with
      clinicopathologic parameters of prognosis in breast cancer. Formalin-fixed,
      paraffin-embedded tissue from 35 patients with breast cancer younger than 35
      years were immunohistochemically stained for BRCA1, H-ras, and c-erbB-2
      expression with monoclonal antibodies. For each antibody, immunoreactivity was
      assessed by a semiquantitative scoring system. Each case was also graded
      according to the modified Bloom-Richardson criteria and evaluated for Ki-67
      labeling index, hormonal status, tumor size, distant metastasis, and axillary
      lymph node involvement. Strong expression of c-erbB-2 and H-ras were observed in
      9 cases (25.7%) and 13 cases (37.2%), respectively. Loss of BRCA1 expression was
      found in five cases (14.3%). Statistical analysis showed that loss of BRCA1
      expression was significantly associated with higher Ki-67 labeling index and
      greater tumor size. In addition, stronger H-ras expression was significantly
      associated with lymph node involvement and distant metastasis. However, c-erbB-2
      immunoreactivity did not show statistical significance with any prognostic
      parameters. We conclude that, although care must be taken not to overstate the
      importance of our results in view of the lack of information on clinical outcome,
      alterations in BRCA1 and H-ras gene expression might be of prognostic importance
      because of the role of H-ras protein on metastatic behavior and the role of BRCA1
      protein on tumor growth. However, c-erbB-2 expression seems to be of no
      importance in the prognosis of breast cancer occurring in young women.

PMID- 10937045
TI  - The immunophenotype of ependymomas.
AB  - The morphologic distinction of ependymomas with epithelial cytology from
      metastatic carcinoma may pose a significant problem in differential diagnosis.
      The known presence of keratin in glioma cells further complicates the issue.
      Using the labeled streptavidin-biotin method with automated staining, we studied
      epithelial and glial marker expression in 52 ependymomas of varying type and
      grade, including 20 epithelial-appearing, 14 glial-appearing, eight mixed
      pattern, and 10 myxopapillary tumors; 38 were low grade and 14 anaplastic. All
      tumors were immunoreactive for glial fibrillary acidic protein (GFAP), and S-100
      protein. Diffuse staining for GFAP was noted in glial-appearing ependymomas
      featuring perivascular pseudorosettes. Diffuse immunostaining for S-100 protein
      was seen in cellular lesions exhibiting epithelial-like features. Staining was
      more diffuse for GFAP than S-100 protein in anaplastic ependymomas. Keratin
      (AE1/AE3) reactivity was seen in 98% of cases, the pattern being similar to that
      of GFAP. The frequency of staining for other keratins varied: wide-spectrum
      keratin (35%), cytokeratin (CK)7 (20%), CAM 5.2 (19%), CK903 (14%), and CK20
      (8%); as a rule, it was scant and limited to occasional cells and processes.
      epithelial membrane antigen (EMA) staining was seen in 36% of all cases and in
      67% of epithelial-appearing tumors wherein it often high-lighted microlumina.
      Aside from AE1/AE3 staining and very infrequent wide-spectrum keratin and EMA
      reactivity, expression of epithelial markers was not seen in anaplastic
      ependymomas. No carcinoembryonic antigen (CEA) positivity was noted in any case.
      Collagen IV reactivity was limited to tumor cell-stroma interfaces. Although
      variable, S-100 protein and GFAP staining is seen in all ependymomas,
      particularly in true and perivascular pseudorosettes. Widespread reactivity for
      keratin AE1/AE3 corresponds closely to the pattern of GFAP staining. Significant
      staining for other keratins or for CEA is inconsistent with a diagnosis of
      ependymoma. EMA reactivity is largely limited to luminal staining of rosettes and
      tubules.

PMID- 10937044
TI  - CD31 immunoreactivity in small round cell tumors.
AB  - CD31 has been shown to be a sensitive and specific marker for endothelial
      differentiation among epithelioid and spindled-pleomorphic human neoplasms.
      However, the role of this marker in the evaluation of small round cell tumors has
      not been evaluated. Formalin-fixed, paraffin-embedded tissue sections from 276
      small round cell tumors, including 85 Ewing's sarcoma/primitive neuroectodermal
      tumors (ES/PNET), 52 rhabdomyosarcomas, 10 extraabdominal polyphenotypic small
      cell tumors, six desmoplastic small cell tumors, 11 neuroblastomas, 23 Wilms'
      tumors, 20 retinoblastomas, 13 esthesioneuroblastomas, and 56 small cell
      malignant lymphomas were stained with CD31 (JC/70A, 1:40), using a modified
      avidinbiotin-peroxidase complex technique, after citrate buffer microwave epitope
      retrieval. Among nonlymphoid small round cell tumors, four of 85 ES/PNET were at
      least focally reactive. No other lesion in this group was positive. In contrast,
      the majority of well-differentiated (11 of 17), intermediately differentiated
      (two of three), and lymphoblastic lymphomas (three of three) were positive. Small
      cleaved lymphomas (three of 13 follicular, one of 13 diffuse) were less often
      reactive, whereas small noncleaved lesions were negative. Although reactivity for
      CD31 in ES/PNET is uncommon, the presence of platelet/endothelial cell adhesion
      molecule in a small cell neoplasm should not in isolation be taken as evidence of
      hematopoietic origin. These results further define the utility of CD31 in the
      evaluation of human neoplasms.

PMID- 10937046
TI  - Immunohistochemical detection of maspin is a useful adjunct in distinguishing
      radial sclerosing lesion from tubular carcinoma of the breast.
AB  - Maspin is a recently described member of the serpin family of protease inhibitors
      that is consistently expressed at high levels in mammary myoepithelial cells.
      This feature was used in the immunohistochemical evaluation of tubular carcinoma
      (TC) and radial sclerosing lesion (RSL) of the breast, and compared with other
      markers of myoepithelial cells. Ten cases of TC and 11 cases of RSL were studied
      for the expression of maspin, alpha-smooth muscle actin (alpha-SMA),
      metallothionein (MT), and S-100 protein by immunohistochemistry. Myoepithelial
      cells stained strongly and diffusely for maspin creating a pattern of an outer
      continuous ring surrounding the epithelium of tubules of all RSLs. This pattern
      was absent in all TCs; however, the single-layered epithelium comprising the
      tubules of two TCs was positive for maspin with a moderate to strong intensity.
      Myoepithelial cells were not positive for MT in a consistent manner. Benign
      nonproliferative epithelium stained focally and weakly for maspin in four of 11
      cases of RSL and was negative for MT in all 11 cases. Foci of mild to moderate
      epithelial hyperplasia noted in five of 11 cases of RSL stained diffusely with a
      weak to moderate intensity for maspin and focally with a strong intensity for MT.
      alpha-SMA was consistently expressed in myoepithelial cells but also in stromal
      myofibroblasts and blood vessels, creating a pattern that was less satisfactory
      than maspin in distinguishing RSL from TC. Immunohistochemical staining for S-100
      protein was of no differential diagnostic value. In conclusion,
      immunohistochemical staining for maspin is diagnostically useful and superior to
      MT, S-100, and alpha-SMA, in distinguishing RSL from TC. The epithelial
      immunoreactivity for maspin in two of 10 TCs merits further investigation from a
      prognostic viewpoint.

PMID- 10937047
TI  - CD99 and cytokeratin-20 in small-cell and basaloid tumors of the skin.
AB  - Although it is classically a deep soft-tissue tumor of childhood, primitive
      neuroectodermal tumor (PNET) can occur at any age and may occasionally involve
      cutaneous sites. Merkel cell carcinoma (MCC) and basaloid neoplasms of cutaneous
      adnexa are the principal diagnostic alternatives to that tumor. The common
      expression of CD99 in PNET and cytokeratin-20 (CK20) in MCC suggests that these
      markers may be of value in this diagnostic setting, but they have not been
      rigorously examined in other small-cell and basaloid lesions of the skin.
      Accordingly, we evaluated CD99 and CK20 reactivity in formalin-fixed, paraffin
      embedded sections of 30 MCC, five cutaneous metastases of pulmonary small-cell
      neuroendocrine carcinomas, 10 primary cutaneous adnexal carcinomas with basaloid
      features, 18 benign basaloid adnexal neoplasms of the skin (nine spiradenomas and
      nine cylindromas), and two cutaneous PNETs, using a standard immunohistologic
      technique and microwave-mediated epitope retrieval. Of the 30 MCC, 12 showed
      crisp membrane staining for CD99. Among the remaining tumors, only the two PNETs
      were positive for that marker. Although the majority of MCCs did not label for
      CD99, the pattern of reactivity in positive cases was indistinguishable from that
      observed in PNETs. Eighteen of 27 MCCs that were stained for CK20 were reactive
      for that protein, in contrast to metastatic small cell carcinomas, cutaneous
      PNETs, and appendageal skin tumors, which were uniformly negative for this
      marker. However, a subset of nine tumors, which were most consistent with MCC on
      clinical grounds, was CD99 positive and CK20 negative. Hence, reliance on CD99
      alone as a diagnostic marker for PNET in this context cannot be recommended.
      Rather, careful assessment of the clinical presentation, together with extended
      immunophenotyping that includes other lineage markers and, when possible,
      cytogenetic analysis for characteristic chromosomal aberrations, remains the best
      means of separating MCC from PNET. Finally, the lack of CD99 reactivity in
      basaloid adnexal neoplasms of the skin suggests a utility in their differential
      diagnosis from cutaneous tumors with neuroendocrine or neuroectodermal
      differentiation.

PMID- 10937048
TI  - Papillary and follicular neoplasms of the thyroid gland. Differential
      immunohistochemical staining with high-molecular-weight keratin and involucrin.
AB  - The morphologic distinction between papillary and follicular neoplasms of the
      thyroid gland can be difficult, especially on small biopsy specimens or in fine
      needle aspirations. To determine whether immunohistochemistry could help in
      achieving the correct diagnosis, we characterized the staining pattern for a
      series of papillary and follicular neoplasms of the thyroid gland. A pilot study
      was performed using a panel of antibodies, including high-molecular-weight
      keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20,
      AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK
      showed strong differential staining between follicular and papillary neoplasms.
      HMWK stained 91% of papillary carcinomas, including follicular variants, with a
      median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms
      with a median of 45% positive cells. HMWK stained only 20% of follicular
      neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed
      strong, although patchy, staining with HMWK and involucrin, whereas those
      follicular neoplasms that did have staining showed a weak, diffuse pattern of
      staining. We believe that HMWK, and involucrin to a lesser degree, could be
      useful in differentiating papillary from follicular neoplasms, especially for
      cytologic cell block material or for cases in which the architectural pattern is
      follicular.

PMID- 10937049
TI  - Gene product immunophenotyping of neuroendocrine lung tumors. No linking evidence
      between carcinoids and small-cell lung carcinomas suggested by multivariate
      statistical analysis.
AB  - Fifty-three neuroendocrine lung tumors (24 carcinoids, one atypical carcinoid,
      five large-cell neuroendocrine carcinomas, and 23 small-cell lung carcinomas)
      were investigated for immunocytochemical expression of several gene products,
      i.e., p53, Rb, bcl-2, c-kit, mdm-2, cdk-4, p21 proteins, and proliferation index
      as assessed by MIB-1. The goal of the study was to explore the relationships
      between histotypes in light of their own gene product-based immunophenotypical
      profiles. To this aim we applied the multiple correspondence analysis, which is
      an exploratory statistical multivariate technique that converts a data matrix
      into a particular type of graphic display in which the rows and columns are
      depicted as points. Such statistical analysis displayed that some categories of
      the gene product-based immunophenotyping variables are grouped in the plot
      identifying three groups: the first group related to carcinoids, the second to
      small-cell carcinomas, and the third to large-cell neuroendocrine carcinomas.
      These data support the evidence that carcinoids and small-cell carcinomas are two
      distinct, apparently immunogenotypically unrelated entities among neuroendocrine
      lung tumors and that atypical carcinoids and large-cell neuroendocrine carcinomas
      seem not to represent intermediate steps between them.

PMID- 10937050
TI  - Optimized cyclin D1 immunoperoxidase staining in mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) has a worse prognosis than MALT lymphoma (MALTL).
      Distinction between MCL and MALTL on purely morphologic grounds can be difficult.
      Cyclin D1 (PRAD1/bcl1) is overexpressed in MCL as a result of a t(11:14) gene
      rearrangement, which leads to overexpression of cyclin D1 mRNA and protein. The
      immunohistochemical detection of cyclin D1 in MCL has been reported by several
      authors to be highly specific with sensitivity ranging from 70%-100%, but
      diagnostic laboratories have reported difficulty in finding a reliable method for
      cyclin D1 immunostaining. The aim of this study was to evaluate and optimize a
      method for detection of cyclin D1 by paraffin section immunoperoxidase staining.
      Sections of routinely processed tissue from five MCL and one splenic marginal
      zone lymphoma (MZL) were immunostained using a mixture of two primary monoclonal
      antibodies and a standard avidin-streptavidin method. Antigen retrieval was
      performed using 1) steam heat in citrate buffer, 2) as in "1" followed by
      sonication for one minute, and 3) as in "2" followed by enzymatic digestion. All
      the above were repeated, with the additional use of catalyzed signal
      amplification (CSA). Later, sections of the same cases, plus three MALTL were
      immunostained as in "2". Steam heat antigen retrieval alone produced the best
      results. All MCL showed positive nuclear staining while the MZL and all MALTL
      were negative. Sonication did not enhance staining noticeably, whereas enzymatic
      digestion produced cytoplasmic staining. CSA increased background staining with
      no significant gain in nuclear stain intensity. We conclude that cyclin D1
      immunostaining of formalin-fixed, paraffin-embedded tissue can be reliably
      achieved by heat induces antigen retrieval and a cocktail of two monoclonal
      antibodies.

PMID- 10937051
TI  - Paraffin section storage and immunohistochemistry. Effects of time, temperature,
      fixation, and retrieval protocol with emphasis on p53 protein and MIB1 antigen.
AB  - It has been observed that immunoreactivity in paraffin sections decreased during
      storage. In this study, stored paraffin sections from both biopsy material and
      cultured cells were assessed for changes in immunoreactivity, using color-based
      image analysis to quantitate extent and intensity of the stainings. For seven of
      the 11 antibodies studied, storage at 20 degrees C for 16 weeks reduced the
      extent of immunostaining compared with that of freshly cut sections. Furthermore,
      increased storage temperatures resulted in a progressive loss of
      immunoreactivity. After 2 weeks of storage, at both 4 degrees C and 20 degrees C,
      p53 protein- and MIB1-antigen expression was significantly reduced regarding
      extent and intensity. The extent of the immunoreactivity reduced more for p53
      protein than for MIB1 antigen, but the intensity did not. Boric acid was used for
      antigen retrieval on sections stored for 12 weeks at 20 degrees C. For both p53
      protein and MIB1 antigen, this resulted in an extent and intensity of
      immunostaining equal to or higher than (MIB1) that obtained in freshly cut
      sections, using citrate buffer. Staining of cultured cells confirmed the results
      from biopsy material on the influence of storage temperature. Fixation time only
      marginally influenced the storage-related decrease in immunoreactivity. In
      conclusion, storage of paraffin sections leads to a varying degree of decreased
      immunoreactivity for several antibodies. The degree is at least partly dependent
      on storage time and temperature but not fixation time. However, this may be
      compensated for by optimizing the antigen retrieval protocol.

PMID- 10937053
TI  - Black thyroid adenoma. Clinical, histochemical, and ultrastructural features.
AB  - A 22-year-old woman with a "hot" thyroid nodule who was being treated with
      minocycline for severe acne vulgaris is presented. A partial thyroidectomy
      specimen revealed a black adenoma. Microscopically, the black pigment was found
      in the follicular cells and the colloid of the adenoma. The pigment was bleached
      with potassium permanganate and was Fontana-Masson stain positive. It was
      negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All
      these feature suggest a melanin-like pigment. However, electron microscopic
      examination revealed a dense osmophilic material present within the lysosomes of
      the follicular cells. No melanosomes were present. Twenty-six previously reported
      cases are reviewed, and the possible mechanisms for the deposition of the pigment
      in the adenoma and its relation to minocycline degradation products are
      discussed.

PMID- 10937052
TI  - Immunohistochemical p16INK4a analysis of archival tumors with deletion,
      hypermethylation, or mutation of the CDKN2/MTS1 gene. A comparison of four
      commercial antibodies.
AB  - The MTS1/CDKN2/p16 gene encoding the p16INK4a tumor-suppressor protein is
      commonly inactivated by homozygous deletion or hypermethylation of the promoter
      in a wide range of human malignancies. In select tumor types, including
      pancreatic adenocarcinomas, intragenic mutations are found in a significant
      percentage of cases. The immunoreactivity of mutant p16 proteins has not been
      comprehensively studied. Moreover, the immunohistochemical properties of
      commercially available antibodies have not been described in detail. We studied
      35 pancreatic adenocarcinomas with a molecularly defined p16 status (16
      homozygous deletions, 3 hypermethylated cases, and 16 tumors with an intragenic
      mutation in one allele associated with loss of the second allele). In addition,
      we studied nine cell lines (three homozygous deletions, three hypermethylated
      lines, and three intragenic mutations). Paraffin sections of the tumors and cell
      blocks were reacted with four different anti-p16 antibodies: polyclonal and
      monoclonal (clone G175-405) antibodies from PharMingen, monoclonal antibody DCS
      50 from Oncogene Science, and monoclonal antibody ZJ11 from Neo-Markers. Optimal
      staining conditions were established for each antibody. The pancreatic carcinomas
      with homozygous p16 deletions were largely devoid of nuclear staining (admixed
      nonneoplastic cells served as internal positive controls); only one
      adenocarcinoma each reacted with DCS-50 and the polyclonal antibody, and five
      were positive with ZJ11, suggesting that nonspecific nuclear staining can occur
      under certain conditions. Antibody DCS-50 produced nuclear staining in all three
      hypermethylated carcinomas, whereas G175-405 stained none of them. Three of the
      four antibodies produced nuclear immunoreactivity in 7 to 14 of the 16 carcinomas
      carrying p16 mutations; G175-405 showed only weak reactivity in one case.
      Cytoplasmic staining was present in all carcinomas and cell lines and with all
      antibodies and therefore cannot be considered specific; it was strongest with
      G175-405. Thus, we found antibody G175-405 to be the most specific, and
      monoclonals DCS-50 and ZJ11 the least specific for wild-type p16. However, the
      former tends to give stronger cytoplasmic background staining. For tumor types in
      which p16 mutations are uncommon, the PharMingen polyclonal antibody may be a
      suitable alternative.

PMID- 10937054
TI  - Molecular morphology goes ultrastructural?

PMID- 10937055
TI  - Immunoelectron microscopy in the age of molecular pathology.
AB  - The introduction of molecular biology-based diagnostic procedures in pathology
      has created substantial expectations in regard to screening, characterization,
      monitoring, and detection of predisposition to a variety of diseases, most
      notably malignant neoplasms. It should be emphasized, however, that molecular
      studies are only one component of the diagnostic process and that more
      traditional methods are still required in the evaluation of tumors and management
      of patients. The data obtained from the molecular biology-based studies must be
      always interpreted in conjunction with the clinical history, immunomorphologic
      findings, and other pertinent ancillary data. Routine evaluation of tissues using
      traditional light microscopy remains the backbone of pathologic evaluation. The
      additive role of molecular diagnostics often depends on how accurate the initial
      evaluation has been. Ancillary techniques such as immunohistochemistry and
      electron microscopy remain essential in properly characterizing diseased tissues
      and in speciation of tumors. Ultrastructural immunolabeling capitalizes on
      combining these two techniques and providing exquisite immunomorphologic
      evaluation. The extra time and effort required are more than compensated by the
      degree of sophistication that can be achieved when this diagnostic technique is
      utilized and the added expense is rather reasonable. The value of molecular
      biology-based diagnostics is potentially questionable if the tissue samples are
      not initially accurately characterized. The question that molecular diagnostics
      may be trying to answer may be the wrong one or the answer obtained may be
      interpreted incorrectly if the context of the clinicopathologic situation has not
      been clearly defined using traditional diagnostic techniques.

PMID- 10937056
TI  - The hyperplasia-to-carcinoma sequence in the breast. Immunohistochemical
      histologic correlations.
AB  - Breast cancer is probably the result of a series of genetic events, each with its
      own histopathologic correlate in the hyperplasia to carcinoma sequence. The
      expression of breast cancer markers in hyperplasia and tumors are well known, but
      few studies have investigated their sequential expression among hyperplastic and
      cancerous lesions within the same breast. Using breast tissue obtained from a
      single procedure, we correlated the immunohistochemical expression of several
      breast cancer markers with the histopathologic stage of proliferative breast
      disease. We selected 14 cases in which various degrees of hyperplasia coexisted
      with carcinoma. Serial sections were reacted with antibodies to DF3, c-erbB-2,
      p53 (DO7 and CM1), B72.3, and cyclin D1. We found that within an individual
      breast, the number of breast cancer markers expressed increased with progression
      from hyperplasia to atypical hyperplasia to carcinoma. Cytoplasmic DF3 was first
      expressed at the level of simple hyperplasia, followed by c-erbB-2 in atypical
      hyperplasia. Overexpression of p53 was confined to carcinomas, and thus appeared
      to be a late event. B72.3 was expressed in three carcinomas and in one atypical
      hyperplasia, although the associated carcinoma was negative. Carcinomas that
      expressed cytoplasmic DF3 and c-erbB-2 were associated with atypical hyperplasias
      that also expressed cytoplasmic DF3 and c-erbB-2, with one and two exceptions,
      respectively. No specific cyclin D1 staining pattern was observed.

PMID- 10937057
TI  - Immunohistochemical measurement of tumor vascular endothelial growth factor in
      breast cancer. A more reliable predictor of tumor stage than microvessel density
      or serum vascular endothelial growth factor.
AB  - Microvessel density counting is commonly proposed as a method of assessing
      angiogenesis. However, results have been difficult to reproduce because of many
      methodological inconsistencies. Vascular endothelial growth factor (VEGF), an
      angiogenic regulator, is also a poor prognostic indicator in breast cancer,
      correlating in many studies with microvessel density. In this study, VEGF and
      microvessel density counting were examined as methods of assessing angiogenesis
      in breast cancer and correlated with tumor stage. A representative tumor section
      was stained with anti-CD34 and anti-VEGF. Microvessel density was evaluated using
      the manual "hot-spot" procedure and a semiquantitative image analysis system.
      Serum VEGF levels were available from an additional nine patients. Results were
      analyzed using Kendall's tau correlation. Tumor stage correlated with tumor VEGF,
      but not with microvessel "hot-spot" or vessel counts. There was no correlation
      between scores obtained from the manual or semiquantitative methods. Serum VEGF
      did not correlate with either tumor VEGF or tumor stage. The prognostic
      importance of VEGF in invasive breast cancer is associated with tumor stage.
      Measurement of tumor VEGF, as an indicator of angiogenesis, is more reliable
      prognostically than measurement of microvessel density or serum VEGF. Routine
      measurement of microvessel density in breast cancer is less reliable.

PMID- 10937058
TI  - Insulin-like growth factor 1 expression in thyroid tumors.
AB  - Insulin-like growth factor 1 (IGF-1) likely is involved in thyrocyte
      proliferation via autocrine mechanisms, but limited data are available on its in
      vivo expression in thyroid neoplasms. This prompted us to explore IGF-1
      expression at the protein and mRNA levels and IGF-1 receptor (IGF-1rec)
      immunoreactivity in normal and neoplastic thyroids (50 adenomas and 53
      carcinomas). We documented increased IGF-1 and IGF-1rec immunoreactivity in
      adenomas (31 of 50 and 40 of 50 cases, respectively) and carcinomas (38 of 53 and
      42 of 53 cases) compared with normal thyroid, which only showed minimal
      immunoreactivity for the ligand and its receptor. A corresponding up-regulation
      of IGF-1 mRNA was documented in carcinomas, whereas adenomas exhibited down
      regulated expression of IGF-1 mRNA. Immunoreactivity for IGF-1 and cognate
      receptor positively correlated with tumor diameter and wide intrathyroidal
      extension but not with patients' gender and age or with the stage of the tumors
      and the occurrence of lymph node metastases. These data emphasize a possible role
      of the IGF-1 system in thyroid tumorigenesis, as indicated by in vitro studies.
      In addition, the evaluation of IGF-1 and IGF-1rec immunoreactivity might have
      clinical implications, because it positively correlates with the aggressiveness
      of these tumors.

PMID- 10937059
TI  - MOC31 immunoreactivity in primary and metastatic carcinoma of the liver. Report
      of findings and review of other utilized markers.
AB  - Differentiating between primary tumors of the liver and metastatic lesions can,
      at times, be difficult. Various histochemical and immunohistochemical methods
      have been used in an effort to better delineate between hepatocellular carcinoma
      (HCC), especially the microglandular variant, primary cholangiocarcinoma, and
      metastatic adenocarcinoma; these ancillary studies can yield less than
      satisfactory results. Recently, anti-MOC31, a monoclonal antibody directed
      against a cell surface glycoprotein, has been shown to be helpful in
      distinguishing between adenocarcinoma and mesothelioma. This study addresses
      whether this antibody might be helpful in distinguishing between HCC, primary
      cholangiocarcinoma, and metastatic adenocarcinoma in the liver. Formalin-fixed,
      paraffin-embedded tissue sections from 15 HCC (including 10 microglandular
      variants), 14 primary cholangiocarcinomas, and 33 metastatic adenocarcinomas (7
      colon, 1 lung, 8 breast, 4 GE jct/gastric, 9 pancreas, 2 small intestine, 1
      renal, 1 ovary) were immunostained with anti-MOC 31 (1:40, Dako) after protease
      digestion and biotin block using a modified ABC technique. Positive staining was
      limited to membrane based reactivity; controls stained appropriately.
      Immunoreactivity for MOC31 was observed in 14 of 14 cholangiocarcinomas and 33 of
      33 metastatic tumors. Staining was diffuse, intense, and readily interpretable,
      with rare exceptions. All 15 cases of HCC were negative. We conclude that
      cholangiocarcinoma and metastatic adenocarcinoma from a variety of sites express
      MOC31; HCC is uniformly negative for this marker. Anti-MOC31 may prove useful in
      the evaluation of liver neoplasms where primary hepatocellular and adenocarcinoma
      enter the differential diagnosis; it is not useful in separating primary
      cholangiocarcinoma from metastatic adenocarcinoma.

PMID- 10937060
TI  - Expression of the five different somatostatin receptor subtypes in endocrine
      cells of the pancreas.
AB  - Knowledge concerning tissue-specific expression of the five somatostatin receptor
      subtypes is of great importance in understanding their physiological function. We
      developed rabbit polyclonal antibodies specific for each human somatostatin
      receptor subtype and report our results concerning the expression in normal
      endocrine pancreatic cells. The antibodies were produced by immunizing rabbits
      with fragments specific for the five cloned somatostatin receptor subtypes.
      Colocalization of these somatostatin receptors with the four major islet hormones
      -insulin, glucagon, somatostatin, and pancreatic polypeptide--was studied in
      normal human endocrine pancreatic cells, using double-immunofluorescence
      staining. High expression of somatostatin receptor subtypes 1, 3, and 4 was found
      in all endocrine pancreatic cells. Somatostatin receptor subtype 2 was frequently
      expressed in alpha and beta cells, whereas expression was low in pancreatic
      polypeptide cells and intermediate in delta cells. Somatostatin receptor subtype
      5 was expressed in most beta and delta cells but almost absent in alpha and
      pancreatic polypeptide cells. There is a variability in the normal expression of
      somatostatin receptor subtypes among the different human endocrine pancreatic
      cells. Knowledge of this expression and the physiological function mediated by
      these receptors will be valuable in the future when considering treatment of
      endocrine disorders.

PMID- 10937061
TI  - Protection against retroviruses are owing to a different form of immunity. An RNA
      based molecular immunity hypothesis.

PMID- 10937062
TI  - Expression of CD34, bcl-2, and kit in inflammatory fibroid polyps of the
      gastrointestinal tract.
AB  - The histogenesis of inflammatory fibroid polyps (IFP) of the gastrointestinal
      tract, focused on the cell of origin of the stromal cells, is a controversial
      subject. The reported CD34 reactivity in gastric IFP has implied a histogenetic
      relationship with a variety of CD34-reactive tumors, including gastrointestinal
      stromal tumors (GIST). In addition to bcl-2, the majority of GIST has expressed
      Kit, suggesting an origin in interstitial cells of Cajal (ICC), which are
      selectively localized around nerve plexuses. Gastric (12) and colonic (two) IFP
      from 13 patients were studied, using antibodies against CD34, bcl-2, and Kit. IFP
      expanded muscularis mucosae with prominent vascular channels, inflammatory
      infiltrates, proliferating stromal cells, and extracellular matrix material.
      Eleven gastric IFP exhibited concentric stromal proliferations (CP),
      particularly, around vessels, glands, and muscle bundles. Their stromal cells
      were CD34 reactive, bcl-2 nonreactive, and Kit nonreactive and showed fibroblast
      like appearances with thin, long cytoplasmic processes. In contrast, one gastric
      and two colonic IFP showed no CP, and their stromal cells were CD34 nonreactive,
      bcl-2 nonreactive, and Kit nonreactive. IFP with CP may have a different
      histogenesis from IFP without CP. IFP with CP may originate from a subpopulation
      of dendritic interstitial cells other than ICC, predominantly localized around
      blood vessels and muscle fibers in muscularis mucosae of the stomach.

PMID- 10937063
TI  - FHIT protein is expressed in benign mesothelium and has no clinical value in
      detecting carcinoma in body cavity effusions.
AB  - The fragile histidine triad (FHIT) protein is a suspected tumor-suppressor gene
      frequently expressed in adenocarcinomas of the lung and other organs. Its
      expression in benign mesothelium has not been reported. This study examined the
      expression of FHIT in mesothelium from benign body cavity effusions. FHIT
      expression was also examined in a diversity of malignant effusions to evaluate
      any value of the FHIT protein to discriminate carcinomas from benign mesothelium.
      Fifty-eight cases of benign and malignant effusions were immunostained using cell
      block material and two different antigen retrieval methods with the ABC method.
      Benign and malignant cases were scored for percentage of cells with strong
      immunoreactivity. Benign mesothelium exhibited strong immunoreactivity for the
      FHIT protein in 32 of 32 (100%) cases, with 26 of 32 (81%) cases having
      expression in at least 50% of cells. Seventeen of 21 (81%) cases of
      adenocarcinomas also exhibited the FHIT protein in at least 50% of tumor cells.
      FHIT expression was also noted in small numbers of other malignancies. The FHIT
      protein is expressed consistently in benign mesothelium as well as many types of
      adenocarcinomas. Immunostaining for this protein has no value in discriminating
      adenocarcinomas from reactive mesothelium.

PMID- 10937064
TI  - Immunohistochemical localization of prostate-specific antigen in ductal
      epithelium of male breast. Potential diagnostic pitfall in patients with
      gynecomastia.
AB  - Enlargement of the male breast is frequently encountered in the course of
      adjuvant antiandrogen therapy for advanced prostate carcinoma. The clinical
      differential diagnosis in this setting includes hormonal imbalance-induced
      gynecomastia, primary breast carcinoma, and metastasis of prostatic carcinoma.
      Biopsy of the lesion with the identification of prostate-specific antigen (PSA)
      plays an important role in establishing the correct diagnosis. Recent studies
      showed that female mammary epithelium may be a significant source of PSA, but its
      expression in male breasts has not been sufficiently studied. We found that
      normal and hyperplastic duct epithelium in gynecomastia exhibited focal, strong
      (+3) PSA immunoreactivity in 5 of 18 cases (28%). In contrast, no PSA reactivity
      was found in eight cases of male breast carcinoma. No reactivity was seen with
      antiprostatic acid phosphatase (PsAP) antibody, in either benign or malignant
      epithelium. Frequent expression of PSA in gynecomastia may, in an appropriate
      clinical setting, cause confusion with metastatic prostatic carcinoma. The lack
      of immunoreactivity for PsAP in male breast epithelium indicates its usefulness
      in the differential diagnosis.

PMID- 10937065
TI  - A highly sensitive nonisotopic detection method for in situ hybridization.
AB  - In situ hybridization is a technique that allows detection of specific DNA and
      RNA sequences in tissue sections. Nonisotopic techniques are fast and give a
      precise localization of the hybridization product, but a drawback is the low
      sensitivity. However, the sensitivity is dependent on the detection system used.
      To evaluate a sensitive in situ hybridization method with nonradioactive probes
      we compared three different detection systems, using biotin-labeled human
      papillomavirus (HPV) 16 probes. The three detection systems included (i) STAV
      FITC method (streptavidin-fluorescein isothiocyanate/alkaline phosphatase anti
      FITC), (ii) APAAP method (mouse anti-biotin/anti-mouse IgG/alkaline phosphatase
      mouse anti-alkaline phosphatase), and (iii) tyramide signal amplification (TSA)
      method (STAV-horseradish peroxidase (HRP)/biotinyl tyramide/STAV-HRP). The in
      situ hybridization methods were tested on CaSki and SiHa cells and two cervical
      carcinomas known to be HPV16 positive. The cells and tissues and been fixed in 4%
      buffered formalin and paraffin embedded. The three different detection systems
      gave satisfactory nuclear staining in CaSki cells (CaSki cells contain > 500
      copies of HPV16 DNA) and the two cervical carcinomas. However, demonstration of
      HPV16 DNA in SiHa cells (SiHa cells contain one to two HPV16 genome copies) was
      possible only by use of the APAAP method. It was concluded that the APAAP method
      provides the best sensitivity among the nonisotopic detection systems and can
      detect single viral copies in formalin-fixed and paraffin-embedded material.

PMID- 10937066
TI  - Protein kinase C (PKC) isoenzymes immunohistochemistry in lymph node revealing
      solution-fixed, paraffin-embedded bladder tumors.
AB  - Protein kinase C (PKC) plays an important role in cellular differentiation and in
      the malignant process. In an earlier study, it was shown that the expression
      pattern of PKC isoenzymes is altered in some tumors compared to their
      corresponding normal tissue. In this study, we evaluated the pattern of PKC
      isoenzyme immunostaining in bladder transitional cell carcinoma (TCC) of
      different grades and stages and normal tissue. Twenty-seven TCC samples and six
      areas of normal bladder mucosa were stained with antibodies specific for the PKC
      isoenzymes: alpha, beta 1, beta 2, delta, and zeta. The sections were scored for
      intensity of staining, and the correlation with grade and stage of the tumors was
      computed. The PKC alpha and beta 2 immunostains were intense in normal urothelium
      and in all evaluated tumors. PKC beta 1 and delta stains were intense in normal
      and low-grade and -stage tumors and weak in high-grade and -stage tumors. The
      opposite trend was found for PKC zeta. PKC isoenzyme expression differs in
      invasive TCC compared to low-grade, low-stage TCC and normal urothelium. The
      value of these findings as a marker of tumor aggressiveness should be further
      assessed.

PMID- 10937067
TI  - Introducing the new journal Archives of Facial Plastic Surgery.

PMID- 10937068
TI  - Modification of the subunit principle for reconstruction of nasal tip and dorsum
      defects.
AB  - This article reports our observations on, and modification of, the subunit
      principle with regard to reconstruction of nasal tip and dorsum defects. Forty
      two patients who underwent reconstruction of a nasal tip and/or dorsum defect
      with a forehead flap were reviewed. These patients were categorized by how the
      subunit principle was used in their reconstruction and graded on the aesthetic
      outcome of the reconstruction. We found that the patients who had both the nasal
      tip and dorsum replaced obtained better results than those who had just 1 subunit
      replaced (P = .008). Review of postoperative photographs shows that the reason
      for this discrepancy in aesthetic outcomes is the line of transition between the
      forehead skin and remaining nasal skin if only 1 subunit is replaced. With this
      observation in mind, we feel that patients undergoing reconstruction of the nasal
      tip and/or dorsum should be evaluated for discrepancies in tissue type between
      the recipient nasal site and forehead donor site. If the tissues are noted to be
      significantly disparate, the reconstructive surgeon may consider replacing both
      subunits with a single forehead flap.

PMID- 10937069
TI  - Modification of the subunit principle.

PMID- 10937070
TI  - Use of intraoperative computed tomography during repair of orbitozygomatic
      fractures.
AB  - OBJECTIVE: To assess the practicality and potential benefits of intraoperative
      computed tomography using a mobile scanner in the operating room during repair of
      orbitozygomatic fractures. SETTING: Level I trauma center. DESIGN: Twenty-five
      patients undergoing open reduction of a unilateral displaced fracture of the
      zygoma and/or repair of a blow-out fracture of the orbit with cranial bone grafts
      were placed into a radiolucent head holder and interfaced with the mobile
      scanner. Spatial vectors were drawn on scans displayed on a computer monitor to
      allow intraoperative side-to-side comparison of the position of the malar
      prominences and orbital walls. Corrections of fracture reduction or bone graft
      position were made as indicated by the comparisons. RESULTS: All scans were
      accomplished without apparent contamination of the surgical field. Major
      revisions were performed, based on the scans, in 2 patients whose displaced,
      comminuted zygoma fractures had been initially reduced with wide exposure of all
      fracture sites. Minor revisions were performed in 3 patients with displaced but
      less severely comminuted fractures that had been reduced without exposure of all
      fracture sites. Bone grafts were repositioned within the orbit in 2 patients with
      large 2-wall blow-out fractures. CONCLUSIONS: Intraoperative computed tomographic
      evaluation of the adequacy of repair of orbitozygomatic fractures is feasible
      with the mobile computed tomographic scanner. The scanner allows correction of
      discrepancies in position of the malar prominences and orbital walls at the time
      of acute repair, rather than during costly, more difficult delayed revisions. It
      may eliminate the need for direct visualization of all fracture sites to ensure
      adequate reduction in selected cases with displaced, comminuted fractures, thus
      decreasing operating room time and expense. Further study is required to fully
      document the cost-effectiveness of this approach to facial fracture management.

PMID- 10937071
TI  - Computed tomography use and repair of orbitozygomatic fractures.

PMID- 10937072
TI  - Comparison of topical anti-ischemic agents in the salvage of failing random
      pattern skin flaps in rats.
AB  - OBJECTIVE: To determine the efficacy of topical anti-ischemic drug therapy in the
      salvage of failing, random-pattern skin flaps. DESIGN: Prospective, randomized,
      placebo-controlled, therapeutic trial. SETTING: Academic medical center.
      SUBJECTS: Sixty-one adult male Sprague-Dawley rats. INTERVENTION: Each
      experimental rat underwent a caudally based random-pattern skin flap using the
      modified McFarlane technique. Rats were randomized to 1 of 6 treatment groups:
      topical nifedipine, topical trolamine salicylate, topical nitroglycerin, topical
      trolamine salicylate-nitroglycerin combination, topical nifedipine-trolamine
      salicylate-nitroglycerin combination, or inert carrier ointment (control).
      Treatment was initiated immediately following flap closure and continued every 6
      hours for 7 days. At the end of the treatment period, animals were euthanized and
      flap survival was determined for each one. RESULTS: Topical anti-ischemic drug
      therapy resulted in a statistically significant reduction in ischemic flap
      necrosis for each drug (or combination) tested relative to the 44.2% mean
      necrosis observed in control animals. Treatment with the combination of topical
      nitroglycerin and topical trolamine salicylate resulted in the best salvage
      response (25.2% mean necrosis) with a statistically significant improvement in
      flap survival relative to both controls and nitroglycerin alone. CONCLUSIONS:
      Topical anti-ischemic agents are effective in reducing ischemic necrosis of
      failing, random-pattern skin flaps in the rat model. Although nitroglycerin,
      trolamine salicylate, and nifedipine possess unique pharmacologic mechanisms of
      action, each drug produced a statistically significant improvement in flap
      survival. The results of this study suggest that topical drug therapy may play an
      important role in clinical salvage of the failing skin flap. Further studies are
      needed to explore the potential of combination drug therapy.

PMID- 10937073
TI  - Orbital fat preservation in lower-lid blepharoplasty.
AB  - In the last 4 years, there have been a few reports concerning unconventional
      management of the fat posterior to the orbital septum (intraorbital) as well as
      periorbital fat located superficial to the orbital septum in a plane both
      superficial and deep to the orbicularis oculi muscle. With reference to
      intraorbital fat, some reports suggest that this fat be preserved and mobilized
      to other areas to recontour the lower lid, while other authors suggest
      repositioning the fat within the bony orbit. To address these new concepts, a
      discussion of the theories behind these approaches is needed.

PMID- 10937074
TI  - Fat preservation to rejuvenate the lower eyelid.

PMID- 10937075
TI  - Secondary rhinoplasty in nasal deformity associated with the unilateral cleft
      lip.
AB  - The secondary nasal deformity of the unilateral cleft lip involves a
      retrodisplaced dome of the ipsilateral nasal tip, hooding of the alar rim, a
      secondary alar-columellar web, and other deficiencies. The sliding-flap
      cheilorhinoplasty effectively corrects these deformities using a laterally based
      chondrocutaneous flap. We modified this technique by using an open rhinoplasty
      approach with the laterally based chondrocutaneous sliding flap. Columellar
      struts and shield grafts were some of the techniques combined with this approach
      to produce optimal results. In a total of 7 patients, we performed both the
      original sliding-flap cheilorhinoplasty and the modified open rhinoplasty, which
      are described and discussed herein. The laterally based sliding-flap
      cheilorhinoplasty is an effective technique for correcting both the secondary
      nasal deformity and the lip scar associated with the unilateral cleft lip.

PMID- 10937076
TI  - Radiofrequency ablation of the nerve to the corrugator muscle for elimination of
      glabellar furrowing.
AB  - Glabellar furrows are caused by hyperdynamic activity of the corrugator
      supercilii muscles. A minimally invasive, percutaneous technique for eliminating
      glabellar furrows is described. An insulated, bipolar needle is inserted
      vertically through the eyebrow skin to entrap the corrugator nerve plexus. To
      confirm proper positioning, a stimulating current is delivered to the needle
      during observation of corrugator supercilii muscle response. Radiofrequency
      energy is then delivered to the needle, thereby ablating the intervening nerve
      tissue. This technique is in the early stage of optimization and is being
      evaluated in an ongoing Stanford University Human Subjects protocol, Stanford,
      Calif. The preliminary results are reported herein.

PMID- 10937077
TI  - The state of the art. Donor site harvest, graft yield estimation, and recipient
      site preparation for follicular-unit hair transplantation.
AB  - The field of hair transplantation has moved beyond the provision of a dense
      frontal hairline to techniques that are designed to provide a natural appearance
      in as few sessions as possible. The concept of the follicular unit has
      revolutionized the preparation of both the grafts and the recipient sites. We
      will describe the mathematics of hair restoration and our techniques for
      determining the length and height of the donor strip for a given number of
      desired follicular-unit grafts. We will also elucidate our technique for cutting
      the follicular-unit grafts using microscopes and transillumination. We now use
      specially designed blades or punches to make shallow slits or slots for recipient
      sites. Striving for teamwork and efficiency is of paramount importance in hair
      transplantation, and we will describe our coordination and training methods as
      well as the role of the surgeon.

PMID- 10937078
TI  - Hypertrophic lip scar following dermabrasion.

PMID- 10937079
TI  - Surgical solution: nasal valve collapse.

PMID- 10937080
TI  - The practice of medicine and its interface with medical regulation.
AB  - Practicing physicians are expected to deliver the highest quality of health care.
      Public demand to establish and implement mechanisms and systems to evaluate the
      fitness and ability of an individual to safely practice medicine resulted in the
      creation of medical boards. Their primary responsibility and obligation is to
      protect the public residing within their jurisdictions from unprofessional,
      improper, and incompetent medical practitioners. Each state provides laws, more
      commonly referred to as a Medical Practice Act, that outline the safe practice of
      medicine within its jurisdiction and set forth the responsibility of the state's
      medical board to regulate that practice. Individuals who want to practice in any
      particular jurisdiction must meet the respective jurisdiction's standards, which
      may include, but are not limited to, educational requirements and clinical
      training.

PMID- 10937081
TI  - Current status of "soft" implant materials for the face.

PMID- 10937082
TI  - Perspective: committed to excellence.

PMID- 10937083
TI  - Nasal tip bossae in rhinoplasty. Etiology, predisposing factors, and management
      techniques.
AB  - OBJECTIVES: To identify preoperative risk factors and surgical techniques that
      influence the risk of developing postoperative nasal tip bossae in rhinoplasty. A
      secondary objective was to review the characteristics, management techniques, and
      outcomes of those study patients with postoperative bossae. DESIGN: Univariate
      and multivariate analysis carried out in a case series. SETTING: Private facial
      plastic surgery practice. PATIENTS: All patients who underwent aesthetic nasal
      surgery that included surgical modification of the nasal tip, and in whom
      documentation was complete and photographic follow-up was available, were
      considered eligible. The study group consisted of 875 patients of whom 37 (4.2%)
      developed bossae postoperatively. MAIN OUTCOME MEASURES: Potential risk factors
      for postoperative bossae included age, sex, previous nasal surgery, preoperative
      tip asymmetry, preoperative lobular bifidity, preoperative bossae, skin
      thickness, surgical tip technique, use of columellar struts, columellar battens,
      lobular crushed cartilage grafts, and tip shield grafts. RESULTS: In the
      univariate analysis, females, patients undergoing primary rhinoplasty, younger
      age groups (12- to 22-year-olds), thin skin, and widened interdomal distance
      (bifidity) were all noted to have moderate or strong associations with nasal tip
      bossae. In the multivariate analysis, the younger age group, thin skin, and
      bifidity were statistically significant and independently associated with nasal
      tip bossae, independent of the type of tip surgery. In addition, clinically
      relevant associations were noted in females and patients undergoing primary
      rhinoplasty. Recognition of risk factors, preventive measures, and treatment
      methods is recommended.

PMID- 10937084
TI  - Orbicularis-levator fixation in double-eyelid operation.
AB  - One of the characteristic features of the East Asian person's eyelids is the lack
      of a supratarsal fold. A relaxed upper eyelid skin, due to the lack of
      supratarsal fixation, causes coverage of the tarsal margin of the upper eyelid.
      Thus the palpebral fissure looks smaller, giving a slit-eye appearance. Unlike
      those lids with a natural supratarsal crease, the levator palpebrae muscle and/or
      aponeurosis does not extend and attach to the pretarsal skin. The purpose of the
      double-eyelid operation is to create a supratarsal fold in the eyelids of Asian
      patients. Numerous surgical procedures have been developed to establish adherence
      between the levator aponeurosis and the eyelid skin. There are 2 main goals for
      this procedure: (1) a smooth, tight skin below the newly created supratarsal
      crease and (2) firm fixation between the levator aponeurosis and the skin to
      prevent relapse to a single eyelid. Most procedures described rely on loose
      cicatrization between the skin and the levator aponeurosis.

PMID- 10937085
TI  - Nasal reconstruction using the inferior turbinate mucosal flap.
AB  - Reconstruction of nasal defects can be a difficult task if large amounts of nasal
      mucosa are missing. We have found the inferior turbinate mucosal flap to be a
      reliable and effective flap in a series of 16 patients undergoing nasal
      reconstruction or repair of septal perforations. Most of these patients had
      insufficient mucosa to use traditional flaps harvested from the nasal floor or
      the lateral nasal wall. Eight patients underwent reconstruction of septal
      perforations, 9 patients underwent nasal reconstruction of large nasal defects
      after tumor extirpation, and 1 patient underwent closure of a palatal fistula.
      Six of the septal perforations were closed completely and 3 were reduced in size
      by 50%. All 11 turbinate flaps used for nasal reconstruction (2 patients had
      bilateral flaps) survived. Two flaps underwent mild superficial epidermolysis
      without flap necrosis or exposure of overlying cartilage grafts. The turbinate
      flap is based anteriorly and provides large amounts of well-vascularized mucosa.
      The turbinate is rotated anteriorly and bivalved and the conchal bone is removed
      to increase the dimensions of the flap. The flap is sometimes staged to allow
      transfer of mucosa to distant sites, such as the septum, the nasal ala, and the
      nasal wall. An anatomical dissection of 10 turbinate flaps on 5 fresh cadaver
      specimens demonstrated an average flap size of 4.97 cm2. The average length of
      the flap was 2.83 cm, which is sufficient length to reach the nasal dorsum. A
      description of the surgical technique and the vascular supply of this flap will
      be discussed.

PMID- 10937086
TI  - The vascular anatomy and angiosome of the posterior auricular artery. A cadaver
      study.
AB  - BACKGROUND: Pedicled flaps based on the posterior auricular artery have been used
      for small auricular and mastoid cavity defects. OBJECTIVE: To precisely define
      the vascular anatomy and angiosome (cutaneous distribution) of the posterior
      auricular artery. METHODS: A fresh cadaver model was used for 3 separate
      investigations, studying the posterior auricular artery. Intra-arterial ink
      injections defined the angiosome, and subtraction angiography and latex injection
      defined the vascular anatomy in relation to bony and soft tissue landmarks.
      SUBJECTS: Eight fresh cadavers, 6 men and 2 women, were used, varying in age from
      58 to 85 years. RESULTS: The posterior auricular artery has a predictable course
      in the posterior auricular sulcus. The branching pattern over the auricle and
      temporal bone and the artery's relationship to bony and soft tissue landmarks
      were consistent. The angiosome includes the anterior and posterior surfaces of
      the auricle and the periauricular skin superiorly, posteriorly, and inferiorly.
      CONCLUSIONS: The investigation documented the consistent vascular anatomy and
      angiosome of the posterior auricular artery. The cutaneous distribution suggests
      that a large pedicled or island flap based on the posterior auricular artery may
      be raised safely as a myocutaneous or myofasciocutaneous flap with temporalis
      fascia and/or periosteum, extending previously published dimensions. Further
      studies may extend the clinical application to include free flaps based on the
      posterior auricular artery.

PMID- 10937087
TI  - Surgery for the dysfunctional nasal valve. Cadaveric analysis and clinical
      outcomes.
AB  - OBJECTIVES: To quantify changes in the cross-sectional area of the nasal valve
      after placement of spreader grafts and flaring sutures and to review clinical
      outcomes after nasal valve surgery. DESIGN: The minimal cross-sectional area of
      cadaveric nasal valves was measured after placement of spreader grafts and
      flaring sutures. Clinical outcomes for patients undergoing functional rhinoplasty
      were retrospectively reviewed. SETTING: Academic medical center. SUBJECTS: Six
      fresh cadaver heads and a review of patients from September 1994 through May
      1998. INTERVENTION: Acoustic rhinometry was performed after placement of spreader
      grafts, flaring sutures, and the two together. Clinically, a site-specific repair
      was performed with spreader grafts and flaring sutures for statically narrowed
      internal nasal valves and cartilaginous battens for dynamic collapse. MAIN
      OUTCOME MEASURE: Cross-sectional areas of cadaveric valves. Functional and
      aesthetic results were determined by nasal patency scores from 1 (complete
      obstruction) to 10 (complete patency) and a rating of postsurgical cosmetic
      changes. RESULTS: Spreader grafts improved the cadaveric minimal cross-sectional
      areas by 5.4% (P > .05), flaring sutures by 9.1% (P > .05), and spreader grafts
      combined with flaring sutures by 18.7% (P < .05). Mean nasal patency scores
      improved from 3.4 to 6.5 (P < .01) with the combination of spreader grafts and
      flaring sutures. Cartilaginous battens improved scores from 2.7 to 6.3 (P < .01).
      CONCLUSIONS: The combination of flaring sutures and spreader grafts has the
      greatest impact on the cadaveric nasal airway. Either technique alone failed to
      have a statistically significant impact on the minimal cross-sectional area of
      the nasal valve. Clinical review confirms significant improvement in nasal
      function using this combination technique.

PMID- 10937088
TI  - Combined erbium:YAG and carbon dioxide laser skin resurfacing.
AB  - OBJECTIVE: To compare clinical and histological results of 2 different protocols
      for cosmetic laser skin resurfacing. DESIGN: Masked comparison of 2 cohort
      groups. PATIENTS: Forty-eight carefully selected patients who met specific
      inclusion and exclusion criteria for cosmetic laser skin resurfacing. Age, sex,
      and skin type were matched in both groups. INTERVENTIONS: Twenty-five patients
      had undergone cosmetic skin resurfacing with 2 impacts of a carbon dioxide laser.
      Another 23 patients underwent a different protocol involving 2 initial impacts of
      an erbium:YAG laser to ablate the epidermis followed by a single impact with a
      carbon dioxide laser. Skin punch biopsy specimens were obtained 1 to 2 weeks
      after the procedure in both groups of patients. MAIN OUTCOME MEASURES: Time to
      reepithelialization, duration of erythema, and patient acceptance were compared
      among 2 patients groups via Student t test. Patients were examined daily until
      reepithelialization, then weekly for 6 weeks, and then monthly for 6 months.
      RESULTS: Mean skin reepithelialization time was 7 days (range, 4-9 days) in the
      combined laser group vs 12 days (range, 9-15 days) in the carbon dioxide laser
      only group (P = .04). Mean duration of erythema was 2.5 weeks (range, 1.5-3
      weeks) in the combined laser group vs 7 weeks (range, 5-13 weeks) in the carbon
      dioxide laser-only group (P = .02). All 23 patients (100%) in the combined group
      but only 15 (60%) of 25 in the carbon dioxide laser-only group were willing to
      repeat their cosmetic laser surgery (P = .04). There were greater and deeper
      coagulative changes in the dermis of patients in the carbon dioxide laser-only
      group compared with those of patients in the combined laser group. CONCLUSIONS:
      The combined laser protocol showed less significant clinical and histological
      morbidity than the carbon dioxide laser-only protocol. Patients preferred the
      combined protocol. Combining these 2 lasers is a safe and patient-friendly
      alternative to using only the carbon dioxide laser.

PMID- 10937089
TI  - Nasal augmentation using Gore-Tex. A 10-year experience.
AB  - OBJECTIVE: To determine on an ongoing basis the safety and efficacy of expanded
      polytetrafluoroethylene (Gore-Tex soft tissue patch and preformed nasal implants)
      as an implant in rhinoplasty. DESIGN: A retrospective study of 309 consecutive
      patients who underwent rhinoplasty, including augmentation with Gore-Tex, during
      a 10-year period. SETTING: Two major academic medical centers and 2 private
      office surgical centers. INTERVENTION: One hundred sixty-two patients (52%)
      presented for primary rhinoplasty; the remaining 147 (48%) presented for revision
      surgery. All received Gore-Tex implants to augment the nasal dorsum and/or base.
      The grafts ranged from 1 to 10 mm in thickness. Follow-up ranged from 5 months to
      10 years, 5 months, with an average of 40.4 months. MAIN OUTCOME MEASURES:
      Clinically noted complications and patient satisfaction. RESULTS: Ten (3.2%) of
      309 grafts became infected and were removed. One graft was removed and 1 graft
      was modified and replaced postoperatively because of excessive augmentation.
      Infection requiring removal occurred in 8 patients (5.4%) undergoing revision
      rhinoplasty and in 2 patients (1.2%) undergoing primary rhinoplasty. Nasal septal
      perforation was present preoperatively in 3 of the patients who developed
      infection requiring removal, and we consider it a contraindication for nasal Gore
      Tex implantation. CONCLUSIONS: Gore-Tex remains an effective implant material for
      nasal augmentation in rhinoplasty. The complication rate in primary cases is low.
      The risk of infection necessitating removal rises significantly in revision
      cases, where its use may still be desirable but must be weighed more carefully.

PMID- 10937090
TI  - Repair of zygomaticomalar complex fractures. The Swiss method.
AB  - The zygomaticomalar complex fracture, also known as the trimalar, tripod, or
      tetrapod fracture, is a fracture commonly encountered by facial plastic surgeons.
      Failure to correctly reduce these fractures can lead to facial asymmetry,
      trismus, diplopia, enophthalmos, and parasthesias. Approaches to the
      zygomaticomalar complex have been well documented in the literature and include
      the transconjunctival lateral canthotomy, subciliary blepharoplasty, brow,
      gingivobuccal, and coronal incisions, or some combination thereof. Fracture
      fixation is accomplished by the internal placement of miniplates and microplates
      across properly reduced fracture lines to resist torsional rotation and
      masticatory distraction. The method of fracture reduction and fixation employed
      at the University Hospital of Bern, Switzerland, shares much with previously
      published and accepted methods of medial and lateral buttress reconstruction, but
      it introduces several original concepts in an attempt to maximize functional and
      aesthetic outcomes.

PMID- 10937091
TI  - Development of Graves orbitopathy after blepharoplasty. A rare complication.

PMID- 10937092
TI  - Radial forearm free flap for soft palate reconstruction.
AB  - Defects of the soft palate resulting from head and neck oncologic surgery
      traditionally have been rehabilitated using a prosthetic obturator. In general,
      the results of soft palate obturation have been satisfactory, with most patients
      achieving velopharyngeal competence during speech and swallowing. However, soft
      palate obturators have several disadvantages. Device stability and retention are
      impaired in patients who are edentulous. In addition, prosthetic obturators cover
      large areas of sensate mucosa in the hard palate, maxillary alveolus, and
      oropharynx, contributing significantly to the loss of sensory feedback from the
      oral cavity and oropharynx. Considerable evidence suggests that sensory
      impairment within the oral cavity and pharynx results in impaired mastication,
      deglutition, and articulation. A minority of patients find palatal obturators to
      be unsatisfactory, secondary to either inconvenience or device discomfort.

PMID- 10937093
TI  - Family violence. A neglected epidemic.
AB  - An obviously well-to-do older woman goes for her yearly physical examination. Her
      physician asked during the routine history, in a nonpejorative fashion, "Has
      anyone harmed you in the last year? Do you feel safe at home?" Much to the
      physician's surprise, she sighs, responding, "Nobody has ever asked me that
      before. I thought I was hiding it better."

PMID- 10937094
TI  - Advancements in aesthetic plastic surgery: the cutting edge. 2.

PMID- 10937095
TI  - Modification of the subunit principle.

PMID- 10937096
TI  - Sir Harold Gillies.

PMID- 10937097
TI  - The validity of ex vivo laser skin treatment for histological analysis. A
      prospective controlled study.
AB  - BACKGROUND: Laser treatment of skin following removal from human subjects has
      been the staple of laser research. However, no study has been done to assess the
      efficacy of ex vivo skin for predicting the behavior of laser treatments in
      living human tissue. OBJECTIVE: To assess the validity of the ex vivo model by
      comparing histological characteristics of skin treated with laser prior to and
      following its removal in rhytidectomy. STUDY DESIGN: Nonrandomized controlled
      intervention study in which each patient served as both experimental subject and
      control for different skin sites. PATIENTS: Ten patients with actinic skin
      changes. INTERVENTIONS: Patients underwent laser treatment to 4 left preauricular
      sites 1 hour prior to rhytidectomy as follows: carbon dioxide laser treatment
      alone, carbon dioxide laser treatment followed by erbium:YAG laser treatment,
      erbium:YAG laser treatment alone, and erbium:YAG laser treatment followed by
      carbon dioxide laser treatment. The skin was examined by a dermatopathologist
      blinded to the identity of each specimen. Untreated skin was also removed and
      immediately subjected to laser treatment identical to that employed in the in
      vivo skin. This skin was examined histologically. MAIN OUTCOME MEASURES:
      Regularity of ablation, depth of the necrotic zone, amount of skin removed,
      degree of collagen injury, and degree of inflammation. RESULTS: There were
      significant differences between the ex vivo and in vivo groups. The ex vivo
      specimens demonstrated more than 10 times the irregularity of ablation of the in
      vivo specimens (irregularity index of 3.0 for the ex vivo group vs 0.25 for the
      in vivo specimens; P < .05). The incidence of collagen injury was slightly lower
      for the ex vivo group (1.0 vs 1.3), as was the degree of inflammation (1.4 vs
      1.5). The greatest differences were the significantly smaller necrotic zone in
      the ex vivo specimens (51 vs 71 microns) and the smaller amount of skin removed
      (118 vs 234 microns). These findings were consistent for all 4 laser treatment
      regimens studied. CONCLUSIONS: Significant differences were found between the in
      vivo and ex vivo models. Irregularity of ablation in the ex vivo specimens was 10
      times that in the living specimens, limiting histological accuracy in the ex vivo
      model. The ex vivo skin model underestimated the amount of tissue ablation. This
      suggests that an in vivo model should be adopted as the standard for laser
      research.

PMID- 10937098
TI  - Autologous fibroblasts for treatment of facial rhytids and dermal depressions. A
      pilot study.
AB  - OBJECTIVE: To assess effectiveness of intradermal injections of autologous
      fibroblasts for the treatment of facial rhytids and dermal depressions. DESIGN:
      Six-month prospective pilot study. Photographs and silicone molds were taken of a
      prominent rhytid or dermal depression from each patient prior to treatment and at
      6 months after treatment. SETTING: Specialty clinic in academic medical center.
      PATIENTS: Ten adults (age range, 24-69 years) who each exhibited a prominent
      rhytid or depressed facial scar. INTERVENTION: A 3-mm postauricular skin biopsy
      specimen from each participant was sent to Isolagen Technologies, Inc,
      laboratories, where a fibroblast cell line was developed. Three injection
      sessions were performed at 2-week intervals; target areas were the study site as
      well as behind the ear. MAIN OUTCOME MEASURES: Subjective improvement scores were
      obtained by each patient and 2 clinicians at every follow-up visit. Skin surface
      topographical features were evaluated with optical profilometry by comparing
      silicone molds before and after injection. Histological analysis was performed on
      a biopsy specimen of the postauricular injection site. RESULTS: Nine of 10
      patients noted a 60% to 100% improvement with the treatment; clinicians made
      similar observations. Size reduction of 10% up to 85% of the study site was
      demonstrated by optical profilometry for every patient. Microscopically, there
      was evidence of increased thickness and density of dermal-layer collagen.
      CONCLUSIONS: Intradermal injection of autologous fibroblasts may be an effective
      treatment option for facial rhytids and depressed scars.

PMID- 10937099
TI  - A 3-year multi-institutional experience with the liposhaver.
AB  - OBJECTIVE: To report a 3-year multi-institutional clinical experience with the
      liposhaver in facial plastic surgery. DESIGN: Nonrandomized, nonblinded, multi
      institutional evaluation of the liposhaver in a clinical setting. INTERVENTIONS:
      Seventy-two patients who presented for facial plastic surgical procedures
      underwent surgery with the liposhaver. Seventy-six liposhaving procedures and 74
      concomitant procedures were performed. Standardized preoperative and
      postoperative photographs were obtained. OUTCOME MEASURE: Subjective evaluation
      by the surgeons who performed the procedures. RESULTS: The liposhaver was used
      successfully in all cases. The fat was cleanly shaved and the contour results
      were even, without dimpling or significant asymmetry. Operative time was
      comparable to that of conventional liposuction. There were no cases of facial
      nerve injury and no evidence of increased bleeding intraoperatively. Two male
      patients had small postoperative hematomas in the immediate postoperative period
      that were successfully treated with conservative measures. An additional patient
      developed a small hematoma on postoperative day 5 that was effectively treated
      with needle aspiration and a pressure dressing. CONCLUSION: This 3-year multi
      institutional report suggests that the liposhaver continues to offer a precise
      alternative to conventional liposuction.

PMID- 10937100
TI  - The effects of resorbable plates on rabbit ear cartilage.
AB  - BACKGROUND: When performing septorhinoplasty, deviated segments of septal
      cartilage can be straightened using cartilage or bone as splinting grafts. In
      some cases, autologous material is not available without an additional surgical
      procedure to harvest cartilage or bone. It is possible that resorbable plates can
      be used to splint and straighten deviated cartilage. Experience using
      bioresorbable rigid fixation devices on cartilage has been limited. OBJECTIVE: To
      examine early histopathologic changes of rabbit ear cartilage and adjacent soft
      tissue following implantation with bioresorbable plates. DESIGN: Nonrandomized,
      placebo-controlled trial. SUBJECTS: Twelve adult New Zealand white rabbits.
      MATERIALS AND METHODS: Ten adult New Zealand white rabbits (20 ears) underwent
      stenting of intact ear cartilage with LactoSorb plates (Lorenz, Jacksonville,
      Fla). Rabbits were killed 28 days after implantation, and the soft tissue,
      plates, and cartilage were harvested and prepared for histological examination.
      As controls, 2 rabbits (4 ears) underwent dissection and closure without
      stenting. RESULTS: Six rabbits experienced superficial skin breakdown on the
      ventral surface of the ear caused by excessive wound tension of the implant. The
      cartilage-plate interface and the surrounding soft tissues stenting the dorsal
      side of the ear remained free of inflammation or necrosis for all animals. Simple
      elevation of the perichondrium revealed no differences in the appearance of the
      cartilage between the control and test rabbits. CONCLUSIONS: Resorbable plates
      have no deleterious effects on cartilage during the first month of implantation.
      While short-term studies have documented the safety and efficacy of using
      bioresorbable plates, further studies are recommended.

PMID- 10937101
TI  - Mersilene mesh chin augmentation. A 14-year experience.
AB  - During the past 20 years, a variety of alloplastic materials have been introduced
      for chin augmentation. Mersilene mesh (Ethicon, Sommerville, NJ), introduced in
      1950, demonstrates many qualities that make it an ideal implant. This article
      reviews the senior author's (S.W.P.) successful 14-year experience using
      Mersilene mesh chin implants. Between 1983 and 1997, 264 patients underwent chin
      implantation procedures. The results show a low rate of infection (0.8%) and
      displacement (1.5%). There were 14 temporary paresthesias and no cases of
      permanent anesthesia. There were no incidences of absorption, rejection, or
      extrusion. Mersilene provides a soft, natural appearance to the chin, and it
      continues to be our choice for chin implantation.

PMID- 10937102
TI  - Closure of mucosal defects over exposed mandibular plates using fibrin glue.
AB  - BACKGROUND: Mandibular plates may become exposed following radiation therapy,
      infection, and mucosal necrosis. This may lead to early removal of the mandibular
      plates with subsequent instability of bone fragments. OBJECTIVE: To compare
      fibrin glue, a bioadhesive, with traditional sutures in closing mucosa over
      exposed mandibular plates in a cat. DESIGN: Prospective matched-pairs analysis.
      SUBJECTS: Nine cats were used, and each cat served as its own control.
      INTERVENTION: Bilateral mandibular plates were fixed on the buccal side of the
      mandible of 9 cats. The surgical defects over the plates were left uncovered.
      After 4 days, the plates on the right side were covered with a mucosal graft
      fastened with fibrin glue, and on the left side the grafts were secured with
      sutures. After 10 days, the grafts were excised and a histological examination
      was performed. RESULTS: The mean operative time for coverage was 2 minutes 11
      seconds for the fibrin glue and 12 minutes 48 seconds for the sutures (P < .001).
      Gross examination revealed granulation or ulceration in 3 of the fibrin and 9 of
      the suture specimens (P < .005). All specimens displayed mild-to-moderate acute
      and chronic inflammation. All sutured specimens showed focal foreign body-type
      giant cells surrounding fragments of bone and suture. Two mandibular plates were
      partially exposed on the fibrin glue side. CONCLUSIONS: The use of fibrin glue to
      cover exposed mandibular plates is safe and well tolerated in cats. Glue
      application requires a shorter operative time and is associated with fewer
      occurrences of granulation and ulceration when compared with suture fixation.
      Further studies are indicated to titrate the concentration of fibrin glue and to
      prevent plate exposure.

PMID- 10937103
TI  - Facial suspension with acellular human dermal allograft.
AB  - OBJECTIVE: To study the efficacy of acellular human dermal (AHD) allograft as a
      material for static slings used to treat ptosis of the oral commissure after
      facial paralysis. DESIGN: In the university facial plastic surgery practices
      (Baltimore, Md, and Albuquerque, NM) of the senior author (J.L.F.), 11
      consecutive patients with facial paralysis were treated with AHD allograft
      slings. Follow-up was 4 to 14 months with 1 patient excluded for inadequate
      follow-up. Six of the remaining 10 patients received radiation therapy. Results
      were considered excellent and designated grade 1 when the affected oral
      commissure was at the same level as the normal commissure. Complete ptosis was
      designated grade 4. Grades 2 and 3 were designated between these extremes.
      RESULTS: All 10 patients showed improvement in the position of the oral
      commissure, in oral competence, and in cheek ptosis. Four patients were grade 1;
      5, grade 2; and 1, grade 3. There were no implant extrusions or infections.
      CONCLUSIONS: The increased biointegration of AHD allografts in comparison with
      alloplastic materials may account for the absence of infection reported in this
      study and the relatively high success rate, especially in patients receiving
      radiation therapy.

PMID- 10937104
TI  - Midline cleft. Treatment of the bifid nose.
AB  - BACKGROUND: Midline facial clefts are rare deformities with a wide range of
      clinical findings from a simple midline vermillion notch to major skeletal
      malformations, including orbital hypertelorism. The bifid nose is a relatively
      uncommon malformation that is frequently associated with hypertelorbitism and
      midline clefts of the lip. The presentation of a bifid nose ranges from a
      minimally noticeable midline nasal tip central groove to a complete clefting of
      the osteocartilaginous framework, resulting in 2 complete half noses. We describe
      our experience with 2 patients with midface clefts who presented with bifid noses
      and a variety of other congenital abnormalities. The anatomy, extensive
      treatment, and complications of the bifid nose are discussed. DESIGN:
      Retrospective case review and literature review. RESULTS: Successful creation of
      an aesthetic nasal contour and normal nasal function was achieved without
      complication via extensive skin, bony, and cartilaginous resection. CONCLUSIONS:
      The bifid nose challenges the rhinoplasty surgeon. A successful outcome is
      dependent on a thorough understanding of the bifid nasal anatomy, proper patient
      evaluation, careful preoperative planning, and meticulous surgical technique.

PMID- 10937105
TI  - The "electric" otoplasty.
AB  - The goal of otoplasty in the treatment of prominauris is symmetrical restoration
      of the ears to an aesthetic position with respect to the side of the head. Most
      commonly, this is accomplished by the creation or enhancement of the antihelical
      fold. In addition, reduction in the projection of the conchal bowl may be
      required with manipulation of the antihelical fold. While myriad techniques exist
      to correct the poorly formed antihelical fold, most involve cartilage weakening
      and suture placement. Herein we describe a simple and effective technique for
      cartilage weakening using electrocautery. Using this technique, otoplasty can be
      performed in a reproducible fashion with a low incidence of complications. In the
      more than 60 patients treated with this technique, there were no complications
      related to the use of the electrocautery, and excellent results were consistently
      obtained.

PMID- 10937106
TI  - Mucous cyst formation after rhinoplasty.
AB  - The development of a deforming nasal-dorsal mass after rhinoplasty is a very rare
      and, for the most part, an avoidable complication. The list of differential
      diagnoses for such a postoperative external nasal lesion ranges from simple soft
      tissue edema or hematoma, which is usually temporary, to more serious lesions,
      such as lipogranulomas, epidermoid inclusion cysts, tumefactive cartilage
      proliferation, and mucous cysts, which can cause permanent deformities. Although
      various nasal tumors, infections, and granulomatous diseases are not specifically
      related to surgery, they should also be considered.

PMID- 10937107
TI  - Closure of a scalp defect.
AB  - In repairing cutaneous defects, the facial plastic and reconstructive surgeon is
      faced with many specialized areas of tissue. Reconstruction of thin eyelid skin
      and thick, sebaceous nasal skin requires different methods. The unique
      characteristics of the scalp make it one of the greatest repair challenges in the
      head and neck region, sometimes requiring multiple different reconstructive
      techniques for the same defect.

PMID- 10937108
TI  - On market share, ethics, and the exercise of public policy. Point of view.
AB  - Make no mistake about it: our ethics drive public policy. The failure to
      understand this has contributed to the alarming proliferation of inquiries and
      legislation about surgery for appearance, those of us who provide it, and the
      facilities in which we work. Office-based surgery, surgery for appearance, and
      the qualifications of physicians who do both are currently under intense scrutiny
      by public agencies. We will examine why this is so, how we might respond, and how
      we can minimize the intensification of such efforts in the future. Although we
      will not be able to crawl off the stage of society's microscope, we may be able
      to get the makers of public policy to use a lower-power objective if we
      demonstrate more ethical scrutiny of our own.

PMID- 10937109
TI  - American Society for Laser Medicine and Surgery: 19th Annual Meeting, April 16
      18, 1999, Orlando, Fla.

PMID- 10937110
TI  - Cilia regrowth of shaven eyebrows.
AB  - OBJECTIVE: To determine if shaving eyebrows can lead to permanent brow loss.
      METHODS: Five patients had a single brow randomly shaven, while the unshaven brow
      served as a control. These patients were evaluated prospectively for brow
      regrowth during 6 months, and photographs were taken at each visit. Two masked
      observers analyzed the final photographs to determine if they could identify the
      side that was shaven. RESULTS: All patients had full brow regrowth by 6 months.
      The masked observers could not identify shaven side with any consistency. One
      female patient with sparser, lighter-colored brow cilia waited longer than the
      other patients for full brow regrowth. CONCLUSION: This small study demonstrates
      for the first time that full brow cilia regrowth is possible after completely
      shaving an eyebrow.

PMID- 10937111
TI  - The tongue-in-groove technique in septorhinoplasty. A 10-year experience.
AB  - BACKGROUND: Correction of the lower third of the nose is perhaps the most
      challenging component of performing a rhinoplasty. The tongue-in-groove (TIG)
      technique provides a method for correcting excess columellar show and maintaining
      correction of caudal deviation. It is also indicated for controlling nasal tip
      rotation and projection while preserving the integrity of the lobular
      cartilaginous complex and may be combined with either the external or endonasal
      rhinoplasty. It is typically used in combination with other septorhinoplasty
      maneuvers. The TIG technique consists of a method by which the medial crura are
      advanced cephaloposteriorly onto the caudal septum into a surgically created
      space between them. OBJECTIVE: To determine the effectiveness of the TIG
      technique to aid in correction of columellar show, a deviated caudal septum, and
      various tip rotation and projection problems. SETTING: Private practices of 2
      authors (R.W.H.K., Houston, Tex, and H.M.T.F., Alexandria, Egypt). PATIENTS: The
      records of 287 patients who underwent TIG rhinoplasties in one private practice
      from 1989 through early 1999 (n = 203) and in another practice from 1994 through
      early 1999 (n = 84) were reviewed. MAIN OUTCOME MEASURES: Physician judgment of
      outcome was based on reduction of columellar show, change in tip rotation or
      projection, narrowing of the columella, and straightening of a deviated caudal
      septum as indicated in preoperative and postoperative photographs taken of all
      but 4 of the 287 patients. Patient judgment of outcome was measured by patient
      requests for revision and patient comments made during follow-up visits. RESULTS:
      Of 287 patients, 278 (97%) had satisfactory to excellent results. Only 9 (3%)
      required revisions related to the TIG technique. Eight of these 9 did not achieve
      enough reduction of columellar show or adequate rotation or projection. A
      repeated TIG technique was used in these 8 patients with satisfactory revision
      results. One of the 9 was overprojected and required revision. Of the 108
      patients who had preoperative caudal septal deviation, none needed further
      surgery. CONCLUSIONS: The TIG technique provides a direct, effective solution to
      columellar show and is a reliable, reproducible method for achieving predictable
      tip rotation and projection. Furthermore, when used in conjunction with
      septoplasty techniques, it helps maintain the correction of a deviated caudal
      septum.

PMID- 10937112
TI  - Resorption beneath silastic mandibular implants. Effects of placement and
      pressure.
AB  - OBJECTIVE: To evaluate the extent to which silicone rubber mandibular implant
      (Silastic; Dow Corning, Midland, Mich) pressure and placement (supraperiosteal or
      subperiosteal) affect underlying mandibular resorption. DESIGN: A randomized,
      controlled animal trial. SUBJECTS: Ten mixed-breed adult hounds. INTERVENTIONS:
      Each animal's mandible was implanted with 6 Silastic blocks, 3 inserted
      supraperiosteally and 3 subperiosteally. Within each grouping of 3 implants,
      pressure was varied from "minimum" to "moderate" to "maximum" by compressing the
      implant with titanium miniplates. After 4 months, the animals were killed and
      their mandibles sectioned for microscopic examination. RESULTS: Mandibular
      resorption occurred in varying degrees beneath all implants by the end of the
      study period. The extent of resorption was consistent with retrospective studies
      in humans. No statistically significant difference was found between
      supraperiosteal or subperiosteal placement of the implants. However, higher
      pressure implants tended to produce less resorption than lower-pressure implants.
      CONCLUSIONS: While some bone resorption seems inevitable with Silastic mandibular
      implants, these results would seem to suggest that the placement of implants
      above or below the periosteum need not be a concern for the surgeon attempting to
      minimize this consequence. On the other hand, increased pressure may actually
      decrease resorption, contrary to current assumptions.

PMID- 10937113
TI  - Evaluation of past and present hair replacement techniques. Aesthetic
      improvement, effectiveness, postoperative pain, and complications.
AB  - OBJECTIVE: To evaluate and compare past and present hair replacement techniques
      of standard grafts, minigrafts, micrografts, scalp reduction, scalp flaps, strip
      harvesting, and punch harvesting procedures with regard to aesthetic improvement,
      effectiveness, postoperative pain, and complications. DESIGN: Three hundred
      surveys were mailed randomly to patients who had undergone hair replacement over
      the last 3 decades. The questionnaire asked patients to rate the level of
      postoperative results and complications in several comparison groups with regard
      to the following factors: itching, pain, swelling, scarring, bleeding, altered
      sensation, poor growth, color and texture, infection, hairline, and natural
      appearance. Each factor was rated by the patients on a scale of 0 to 3 (0, none
      [best]; 1, minimal; 2, moderate; and 3, worst [severe]). SETTING: Private facial
      plastic surgery practice. METHODS: A hypothesis about each set of survey
      questions was formed based on general trends in patient responses, also known as
      the null hypothesis; chi 2 tests were conducted for each of the survey questions
      to determine the statistical trend with a certain level of confidence. The
      weighted arithmetic mean of the expected response was used for the varying number
      of patients responding to each question. Using the chi 2 test, the formulated
      hypotheses can be accepted or rejected based on the observed and expected
      responses. RESULTS: Between 1981-1990 and 1991-1996, there was a reduction of 38
      percentage points in the number of standard graft procedures performed, an
      increase of 31 percentage points in the number of minigraft procedures, and an
      increase of 48 percentage points in the number of micrograft procedures. The
      complication rate was 31% lower for minigraft procedures compared with standard
      graft procedures and 29% lower for micrograft procedures compared with minigraft
      procedures. The complication rate was 59% lower for strip harvesting procedures
      compared with punch harvesting procedures. CONCLUSIONS: Newer hair replacement
      techniques have improved aesthetic results, with lower morbidity and complication
      rates. These improvements are responsible for the increase in the level of
      satisfaction of patients undergoing hair replacement surgery today.

PMID- 10937114
TI  - Quantification of skin elasticity changes associated with pulsed carbon dioxide
      laser skin resurfacing.
AB  - BACKGROUND: While skin resurfacing using pulsed carbon dioxide lasers appears to
      have a skin-tightening effect clinically, the debate continues over its actual
      effects on dermal collagen. OBJECTIVES: To provide quantitative measures of skin
      elasticity changes associated with pulsed carbon dioxide laser skin resurfacing
      and to introduce to the facial plastic surgery community the Cutometer SEM 575
      skin elasticity meter, an instrument that is useful in the measurement of skin
      elasticity. SETTING: University-based facial plastic surgery clinic and wound
      healing laboratory. DESIGN: Intervention. MAIN OUTCOME MEASURES: Measurements
      taken prior to and 6 months after procedure. SUBJECTS AND INTERVENTION: Thirty
      two patients undergoing pulsed carbon dioxide full-face laser skin resurfacing
      participated. There were 12 test sites measured in 6 aesthetic units per
      participant. The Cutometer SEM 575 skin elasticity meter was used to measure skin
      elasticity changes accompanying this procedure. This device measures skin
      deformation with an accuracy of 10 microns. RESULTS: The change in elastic
      recovery (Ur/Ue) was determined. At all 6 of the facial sites, there was a
      statistically significant increase in skin elasticity (P < .001). Overall, there
      was an 18.2% improvement in skin elasticity. Site-specific changes ranged from 9%
      (forehead) to 22% (prejowl and periorbital). CONCLUSIONS: Skin resurfacing with
      the pulsed carbon dioxide laser produces a true skin-tightening effect. The
      Cutometer is a valuable instrument that permits accurate quantification of skin
      elasticity and may be useful in the evaluation of other facial plastic procedure
      results.

PMID- 10937115
TI  - Digital vs 35-mm photography. To convert or not to convert?
AB  - OBJECTIVES: To compare the quality of images generated from a conventional 35-mm
      camera with those generated from various digital cameras; and to note the costs
      of the cameras and ease of use. DESIGN: A prospective, randomised, independent
      analysis of specific facial images taken with a 35-mm camera and 3 digital
      cameras by 3 facial plastic surgeons who were blinded to camera type. SETTING: An
      academic medical center. SUBJECTS: Thirteen volunteer subjects ranging from age
      27 to 58 years. MAIN OUTCOME MEASURES: The overall quality, focus, distortion,
      trueness of color, resolution, contrast, and presence of shadows were evaluated
      for each image. Attributes were scored on an ordinal scale of 1 to 5. A 1-way
      analysis of variance was used to test whether the average scores across cameras
      were significantly different. Results using analysis of variance did not differ
      from the results using a nonparametric Kruskal-Wallis test. When significant
      differences were found, the Duncan multiple range test was used to group
      significantly different scores. RESULTS: The null hypothesis that there is no
      difference between photographs taken with the various cameras was rejected (P <
      .001) for each of the image attributes. The images produced by the 35-mm camera
      (Nikon 6006) had the best overall quality, followed by the Olympus D600L, Kodak
      DCS 315, and Olympus D320L digital cameras. Differences in individual attributes
      between several of the cameras in each category were statistically significant (P
      < .05). CONCLUSIONS: The 35-mm camera produced the best overall image quality and
      ranked first for each of the individual attributes analyzed in this study. The
      Olympus D600L digital camera placed second in overall quality, but there was no
      statistically significant difference in focus, distortion, and resolution
      compared with the images generated by the 35-mm camera. The Olympus D600L digital
      camera also ranked second in color, contrast, and shadow. The Kodak DCS 315 and
      D320L digital cameras finished well behind the 35-mm camera in most categories.
      Although the 35-mm photographs were superior to the digital images, the surgeon
      should also consider other factors before selecting a system for
      photodocumentation of surgical results.

PMID- 10937116
TI  - Feedback-controlled laser-mediated cartilage reshaping.
AB  - OBJECTIVE: To demonstrate feedback-controlled laser-mediated cartilage reshaping
      using dynamic measurements of tissue optical properties and radiometric surface
      temperatures. DESIGN: Flat cartilage specimens were reshaped into curved
      configurations using a feedback-controlled laser device. MATERIALS: Fresh porcine
      nasal septum, stripped of perichondrium and cut into uniform strips (25 x 10 x
      1.5-2.1 mm) with a custom guillotine microtome. INTERVENTIONS: Cartilage
      specimens secured in a cylindrical reshaping jig (2.5 cm in diameter) and
      irradiated with an Nd:YAG laser (lambda = 1.32 microns, 25 W/cm2, 50-Hz pulse
      repetition rate). During laser irradiation, radiometric surface temperature was
      measured along with changes in forward-scattered light from a diode probe laser
      (lambda = 650 nm, 5 mW), using a lock-in detection technique. Sequential
      irradiation of the specimen outer surface was made (3 laser passes).
      Characteristic changes in tissue temperature and light-scattering signals were
      used to terminate laser irradiation. RESULTS: Effective reshaping was
      accomplished for both thin (1.5-mm) and thick (2.1-mm) specimens. Following
      reshaping, specimens were stored in saline solution at 4 degrees C for 21 days.
      No return to the original flat configuration was noted during this period.
      CONCLUSIONS: The prototype device effectively reshapes flat native porcine
      cartilage into curve configurations. The use of optical and thermal signals
      provides effective feedback control for optimizing the reshaping process.

PMID- 10937117
TI  - Epidemiology of facial injury in female blunt assault trauma cases.
AB  - BACKGROUND: Etiology of trauma in the female population differs from that of the
      male population. To date, domestic violence has been researched extensively, but
      little has been published about the epidemiology of facial injury in the female
      population. OBJECTIVES: To analyze the differences in the circumstances under
      which males and females are injured, to identify gender-specific patterns of
      injury, and to assess whether differences in the demographics, health status, and
      drug-use profile exist between female and male assault cases and whether these
      factors lead to a difference in outcome. METHODS: A cohort of 91 female assault
      cases was compared with a control group of 706 males with similar injuries
      resulting from blunt assault trauma. Information was gathered by retrospective
      review of 797 consecutive cases requiring admission for facial injuries resulting
      from blunt assault trauma. Fisher exact, chi 2, and t tests were used to assess
      statistically significant differences between the male and female cohorts.
      RESULTS: The female cohort comprised 12% of all cases admitted for blunt assault
      facial trauma. One third of female blunt assault facial trauma patients were
      subjects of domestic violence. Statistically significant differences were found
      between males and females for the type of assault (rape, domestic violence,
      altercation, etc) with P < .0001. Females were more likely to be admitted with
      soft tissue injury only but no fracture (P < .05), less likely to be assaulted
      with a weapon, and unlikely to be involved in an altercation, gang violence,
      arrest, or robbery. Females were also less likely than males to be injured while
      intoxicated (P < .05). Incidence of specific injury patterns and outcomes,
      however, were similar between the 2 groups. CONCLUSION: The present data support
      the hypothesis that the female blunt assault facial trauma population represents
      a distinct epidemiological entity, with significant differences in the
      circumstances of injury, mechanism of assault, and role of intoxication in the
      incidence of injury. The prevalence of facial trauma in female assault cases
      makes it critical for the facial plastic surgeon to be vigilant in the evaluation
      and treatment of these patients.

PMID- 10937118
TI  - Efficacy of octyl-2-cyanoacrylate tissue glue in blepharoplasty. A prospective
      controlled study of wound-healing characteristics.
AB  - OBJECTIVE: To compare the surgical efficacy and wound-healing characteristics of
      the tissue adhesive octyl-2-cyanoacrylate (approved by the Food and Drug
      Administration) with traditional suture closure in upper blepharoplasty. METHODS:
      Prospective, randomized, blinded study comparing cosmetic and functional outcome
      and time efficiency. Twenty subjects underwent upper eyelid blepharoplasty. Each
      patient had a control side and an experimental side determined randomly. One
      eyelid incision was closed with octyl-2-cyanoacrylate (Dermabond; Ethicon Inc,
      Somerville, NJ) tissue glue, and the other with 6.0 suture (polypropylene or fast
      absorbing gut). Comparisons were performed for the time for closure by each
      method, wound healing, and patient satisfaction. Macrophotographs of the wounds
      at 1, 2, and 4 weeks after surgery were graded by 5 observers blinded to the
      closure method, using a 10-point scale and a modified Hollander wound evaluation
      scale. RESULTS: No statistically significant difference was found between the
      quality of octyl-2-cyanoacrylate closure and suture closure at 1 month. There
      were no differences in wound complications, duration of healing, inflammation, or
      final incision appearance. By 2 weeks, the sides were indistinguishable in 15
      (75%) of the patients. Time for closure averaged 7 minutes with suture and 8
      minutes with glue. CONCLUSIONS: Octyl-2-cyanoacrylate glue is an excellent
      alternative to suture closure, producing equivalent quality of closure at all
      time points and no difference in appearance. This adhesive was sufficient to
      withstand the forces of closure in upper eyelid blepharoplasty without dehiscence
      in the absence of sutures.

PMID- 10937119
TI  - Nasal reconstruction in the elderly patient. The case for not letting age
      determine method.
AB  - OBJECTIVES: To review a series of nasal reconstructive procedures in elderly
      patients, and to discuss management issues related to reconstructing nasal
      defects in patients 80 years and older. DESIGN: Retrospective review identifying
      patients 80 years and older undergoing significant nasal reconstructive surgery.
      SETTING: University and private practice settings. PATIENTS: Patients 80 years
      and older requiring significant nasal reconstructive surgery, with nasal defect
      large enough to require a forehead flap for skin resurfacing. Patients whose
      defects were allowed to granulate or who had skin grafts were excluded.
      INTERVENTION: Nasal reconstructive surgery using advanced surgical techniques
      such as forehead flaps and cartilage grafts. MAIN OUTCOME MEASURES: Complications
      related to surgery or use of anesthesia and whether patients believed the effort
      and resources required to complete the nasal reconstruction were worth it.
      RESULTS: Fifteen patients 80 years and older underwent nasal reconstructive
      surgery using forehead flaps. In addition, 5 patients had intranasal mucosal
      grafts and 6 had cartilage grafts. There were no instances of anesthetic or
      perioperative morbidity or mortality. In addition, all flaps completely survived,
      and results were judged as good to excellent. CONCLUSIONS: Actuarial evidence
      shows that a 90-year-old American woman has a 40% chance of living to be 95 years
      old. Presently, with the improved level of functioning of octogenarians and
      nonagenarians, we are also concerned with their facial appearance, and want to
      use the optimum reconstructive technique. The decision of what type of
      reconstructive surgery to perform should not be based simply on a patient's age
      but must also take into account the patient's mental status and wishes, and
      medical condition. Our evidence supports the concept that, in the appropriately
      chosen patient 80 years and older, forehead flaps and cartilage grafting can be
      performed without significant morbidity.

PMID- 10937120
TI  - Management of infraorbital dark circles. A significant cosmetic concern.
AB  - Despite the frequency with which it occurs, little has been written in the
      scientific literature on the treatment of infraorbital dark circles. I have
      developed a technique that simultaneously treats the 2 contributing causes of
      these circles: hyperpigmentation of skin and pseudoherniation of orbital fat. The
      technique involves simultaneous transconjunctival blepharoplasty and deep-depth
      phenol chemical peel. Successful outcomes have been obtained in patients with
      Fitzpatrick classification skin types 1 to 5, with a low incidence of
      complications. Adequate preoperative counseling regarding prolonged erythema and
      careful postoperative monitoring with, if necessary, medical intervention are
      essential if both surgeon and patient are to be satisfied with the outcomes.

PMID- 10937121
TI  - Treatment of occipital acne keloidalis by excision followed by secondary
      intention healing.
AB  - OBJECTIVE: To demonstrate the principle of excision with healing by secondary
      intention in the treatment of occipital acne keloidalis, a chronic, inflammatory
      condition characterized by inflammation and hypertrophic scarring on the
      posterior aspect of the neck and the occipital aspect of the scalp. SETTING:
      Academic teaching institution. METHODS: Five consecutive patients with massive (>
      10 x 15-cm) occipital keloids, all actively infected and growing, were treated by
      excision of the lesion deep to the dermis and hair follicles. Aggressive local
      wound care of the wound followed, with the end point being complete
      reepithelialization of the region. RESULTS: Complete wound closure took place in
      all patients within 6 to 10 weeks. No complications or recurrences occurred.
      Cosmetic results were judged as fair to good. Follow-up ranged from 2 months to 4
      years. CONCLUSIONS: Successful treatment of occipital acne keloidalis with direct
      excision and secondary intention wound healing is demonstrated. While cosmetic
      results are not optimal, this form of treatment has produced stable scar beds
      without return of infection or keloids.

PMID- 10937122
TI  - The contoured auricular projection graft for nasal tip projection.
AB  - In all rhinoplasty surgery, the universal need exists to increase, decrease, or
      preserve existing tip projection. When proper tip projection is lacking, a
      variety of techniques are useful for improving projection. We describe a valuable
      technique for tip projection, particularly useful and indicated in the Asian
      rhinoplasty, African American rhinoplasty, and in certain revision rhinoplasties.
      In the past 15 years, the senior author (M.E.T.) has used the contoured auricular
      projection graft in selected patients for achieving satisfactory tip projection
      in patients with blunted tips. The aesthetic outcomes have been predictable,
      pleasing, and reliable for the long term. Precision pocket preparation for
      auricular conchal cartilage graft placement is key to symmetry and projection of
      the final outcome. The results yielded a rounded nasal tip that may be more
      natural-appearing in Asians, African Americans, and selected patients with
      revision rhinoplasty. The contoured auricular projection graft provides a highly
      useful graft for the nasal tip.

PMID- 10937123
TI  - Extended applications for endoscopic forehead surgery.
AB  - Endoscopic equipment and specially designed elevators and dissecting instruments
      provide access to the forehead and scalp region through minimal incisions. This
      technique is now widely accepted for aesthetic forehead and browlifts. To our
      knowledge, however, it has not previously been used in reconstructive forehead
      and scalp surgery. We carried out a retrospective review of 5 cases involving
      patients who underwent reconstructive scalp and frontal bone defect surgery: 2
      patients had frontal defects that were contoured with expanded
      polytetrafluoroethylene (Gore-Tex; WL Gore & Assoc, Phoenix, Ariz) inserted
      endoscopically; 2 patients had scalp soft tissue defects that were treated with
      wide subgaleal undermining and endoscopically guided galeotomies that resulted in
      primary closure; and 1 patient was treated for facial paralysis to improve the
      aesthetic result. We conclude that aesthetic endoscopic surgical techniques and
      equipment can be used in reconstructive therapy for patients with bony and soft
      tissue defects of the scalp and forehead.

PMID- 10937125
TI  - The advanced rhinoplasty course.

PMID- 10937124
TI  - An unexpected occurrence of acute contact dermatitis during rhinoplasty.

PMID- 10937126
TI  - Jacques Joseph. Surgical sculptor.

PMID- 10937127
TI  - Genetics of inherited epilepsies.

PMID- 10937128
TI  - Clonic convulsion caused by epileptic discharges arising from the human
      supplementary motor area as studied by subdural recording.
AB  - In order to help clarify the mechanism of tonic convulsion, which is commonly
      seen in supplementary motor area (SMA) seizures, we investigated the temporal
      relationship between ictal discharges arising from the SMA and the associated EMG
      discharges in the foot, in a patient with SMA seizures, prior to surgical
      treatment. The patient's intractable seizures consisted of tonic followed by
      clonic convulsion of the left foot also involving at times, the left hand. Ictal
      EEGs were investigated by subdural electrodes placed on the SMA-proper and pre
      SMA, which were defined by cortical stimulation and by recording cortical-evoked
      potentials. Interictally, repetitive spike discharges were seen at the pre-SMA.
      Each seizure initially had a tonic phase associated with an electrodecremental
      EEG pattern. It was followed by clonic convulsion as shown by clonic EMG
      discharges of the left tibialis anterior (TA) muscle. It had a duration of 300 to
      500 msec, and on each occasion a positive cortical activity at the pre-SMA
      preceded the EMG onset by 110 msec, and a negative spike at the SMA-proper
      preceded the EMG onset by 50 to 60 msec. Epileptic discharges originating from
      the pre-SMA spread to the SMA-proper and possibly also to the primary motor
      cortex (MI) in this patient. Since both SMA-proper and MI could elicit EMG
      discharges through the independent corticospinal tracts having different
      conduction velocities, even a single spike arising from the SMA could give rise
      to a long EMG burst, which may play some role in the tonic convulsion which
      characterizes SMA seizures.

PMID- 10937129
TI  - Clinical and video-polygraphic features of epileptic spasms in adults with
      cortical migration disorder.
AB  - The International Classification of Epileptic Syndromes considers epileptic
      spasms to be typical seizures of West syndrome. Literature reports show that
      spasms are present in epileptic syndromes other than West syndrome but there are
      few data on their characteristics in adults. We describe ictal, clinical and
      video-polygraphic findings in three patients (aged 21, 32 and 57 years) with
      epileptic spasms and with diffuse (case 2), focal right fronto-parietal (case 1)
      and bi-opercular (case 3) pachygyria. Spasms had been present since the ages of 1
      month, 11 and 27 years respectively. Only one patient is mentally retarded. Two
      of our patients (cases 2 and 3) have partial seizures. Ictal polygraphic studies
      showed a positive, diffuse, high amplitude slow wave activity during spasms, with
      superimposed fast activity, followed by a diffuse flattening in all cases with a
      typical muscle pattern. Epileptic spasms, as typically described in West
      syndrome, can maintain the same semeiological and electroencephalographic
      features during adulthood in certain patients with cortical dysplasia.

PMID- 10937130
TI  - Idiopathic partial epilepsy: electroclinical demonstration of a prolonged seizure
      with sequential rolandic and occipital involvement. Seizure spread due to
      regional susceptibility?
AB  - Benign rolandic epilepsy (BRE) and childhood epilepsy with occipital paroxysms
      (CEOP) are overlapping in age range of presentation. Some children have been
      reported to manifest occipital and rolandic seizures, as distinct events.
      However, the presence during the same seizure of rolandic and occipital symptoms
      is exceptional. We present a 7-year-old boy with BRE in whom we video-EEG
      recorded two seizures at 4 years of age. The first episode was a classic rolandic
      seizure during sleep, while the second was prolonged with initial rolandic and
      late occipital involvement. It is possible that a rolandic seizure, in a child
      within the age range of both BRE and early onset CEOP, could spread to
      selectively involve the occipital lobe, because there is susceptibility of
      cortical neurons of both areas to develop seizures at this age in idiopathic
      partial epilepsies.

PMID- 10937131
TI  - The localizing value of ictal SPECT in children with tuberous sclerosis complex
      and refractory partial epilepsy.
AB  - Although multiple cortical tubers are a hallmark of tuberous sclerosis complex
      (TSC), seizures often originate from a single tuber, making excisional surgery a
      therapeutic option for intractable patients. To assess the role of ictal single
      photon emission computed tomography (SPECT) in defining the epileptogenic tuber,
      we reviewed videoelectroencephalography (V/EEG) data, magnetic resonance imaging
      (MRI) and SPECT scans of 15 patients (aged 3 months to 15 years, mean 5.1) with
      medically resistant partial seizures and TSC. SPECT scans were performed using Tc
      99m-hexamethylpropyleneamine oxime (HMPAO) injected within 30 seconds of
      electrographic seizure onset and were graded on a scale from 1 to 5 (1 weakly
      perfused, 5 strongly perfused). The scalp EEG revealed localized seizure origin
      in ten patients; five had concordant hyperperfused SPECT regions consisting of
      comma-shaped areas surrounding hypoperfused areas in the candidate tuber.
      Strongly hyperperfused regions (grade 3-5) were noted in two patients whose ictal
      EEG patterns were characterized by sustained, rhythmic fast activity or spiking.
      The other five patients had nonlocalizing or poorly sustained ictal EEG patterns;
      one patient in this group had focal hyperperfusion. Invasive EEG recordings in
      two patients revealed propagated EEG patterns that correlated with the ictal
      SPECT findings. These findings indicate a strong correlation between ictal SPECT
      and ictal scalp EEG, especially when there are sustained rhythmic fast ictal EEG
      patterns.

PMID- 10937132
TI  - Pure photosensitive ictus emeticus.

PMID- 10937133
TI  - Video-EEG and ictal SPECT in three patients with both epileptic and non-epileptic
      seizures.
AB  - We report scalp EEG and ictal SPECT findings in epileptic (complex partial) and
      non-epileptic seizures in three patients who experienced both types of event
      during presurgical investigation of medically intractable epilepsies. In all
      three patients, ictal SPECT showed localizing changes in cerebral blood flow
      during epileptic seizures, but showed no change during pseudoseizures. In two
      patients, the physical manifestations of the pseudoseizures were similar to those
      of the epileptic seizures, supporting the contention that physiological
      activation is unlikely to mimic ictal perfusion changes. In one patient, the EEG
      recording was rendered difficult to interpret by muscle artefact, while SPECT was
      clear and showed no change. SPECT is not a primary tool for diagnosis of
      pseudoseizures, but when patients undergoing presurgical investigation are
      injected during pseudoseizures, then SPECT is unlikely to show misleading
      perfusion changes due to activation effects, and may aid diagnosis where there is
      muscle artefact on EEG.

PMID- 10937134
TI  - Benign myoclonus of early infancy.
AB  - Benign myoclonus of early infancy, first described by Fejerman and Lombroso, is a
      paroxysmal phenomenon of the first 2 years of life which occurs in neurologically
      healthy infants during wakefulness, and is usually triggered by excitement or
      frustration. We studied the neurophysiological features of the phenomenon in five
      children, aged 7 to 11 months, who were monitored by video-EEG recording, and by
      polygraphic recording in 3 of the 5 cases. The phenomenon is characterized by a
      shudder-type, paroxysmal motor manifestation involving mainly the trunk and
      sometimes the head, associated with tonic limb contractions of variable
      intensity, from hardly noticeable to more sustained. The EEG counterpart never
      showed modifications, the polygraphic study demonstrated a brief tonic limb
      contraction. The clinical manifestation should not be confused with the spasms of
      epileptic infantile spasms syndrome, or with tonic reflex seizures of early
      infancy. Although the phenomenon is already widely known, its polygraphic
      recording is rarely reported in literature. The polygraphic data of our patients
      contributes to the diagnosis and understanding of the pathophysiology of this
      paroxysmal manifestation.

PMID- 10937135
TI  - Repetitive sleep starts in neurologically impaired children: an unusual non
      epileptic manifestation in otherwise epileptic subjects.
AB  - Sleep starts, also called hypnagogic or hypnic jerks, are bilateral, sometimes
      asymmetric, usually single, brief body jerks that coincide with sleep onset. We
      describe sleep starts occurring repetitively in three epileptic children with
      spastic-dystonic diplegia and mental retardation. Repetitive sleep starts began
      at age 18 months in two children and at 9 months in the third. All three children
      had had feto-neonatal asphyxia; two presented with spastic and one with dystonic
      tetraparesis. One had West syndrome and two had partial motor seizures in the
      first year of life. Seizures were controlled in all three patients by
      antiepileptic drug therapy. Video/EEG recordings of all the children during the
      afternoon nap revealed clusters of sleep starts during the transition between
      wakefulness and sleep. Cluster lasted 4-15 min and comprised from twenty to
      twenty-nine contractions. The EEG counterpart of the event sometimes showed an
      arousal response, at times inducing complete awakening. Repetitive sleep starts
      should be recognized and clearly differentiated from epileptic seizures,
      especially if they appear in epileptic subjects. In neurologically compromised
      patients, they could represent an intensification of an otherwise normal event,
      due to the lack of strong inhibitory influence of the pyramidal tract resulting
      from the pyramidal lesion.

PMID- 10937136
TI  - Epilepsy and perisylvian lipoma/cortical dysplasia complex.
AB  - Intracranial lipomas are congenital malformations composed of mature adipocytes.
      They are usually located in the midline, particularly in the pericallosal region,
      a hemispheric location accounting for only 3 to 7% of cases. Review of the
      literature found 21 previous cases of hemispheric lipoma. Although hemispheric
      cerebral lipomas are rare, association with epilepsy appears to be frequent. We
      have recently studied two patients in whom epilepsy was the first clinical
      manifestation of hemispheric cerebral lipoma in the sylvian region. The patients
      presented with simple motor partial seizures as the first manifestation of the
      lesion. Neurological examination was normal. MRI disclosed in both cases a lesion
      involving the sylvian fissure with characteristics of the lipid signal. MRI also
      demonstrated abnormalities involving the cerebral cortex in the vicinity of the
      lesion (pachygyria-like aspect). Partial excision of the lesion was achieved in
      one patient but was followed by a worsening of seizures and neurological
      condition (hemiparesis). According to the literature, the prognosis for epilepsy
      in patients with hemispheric lipoma appears good. Several other arguments support
      non-surgical management: the lesion is benign and can be identified with a high
      degree of certainty by imaging; surgery is technically difficult due to adherence
      to adjacent vascular and cerebral structures and hypervascularity; location near
      functional brain tissue increases the risk of postoperative sequelae. In
      addition, mechanisms of epilepsy probably involve vascular and cortical dysplasic
      abnormalities. In consideration of the complexity of the lesion, hemispheric
      lipomas are more appropriately classified with localized cortical malformations
      rather than as simple extracerebral malformations.

PMID- 10937137
TI  - Scope and presumed mechanisms of hallucinations in partial epileptic seizures.

PMID- 10937138
TI  - Epilepsy and paroxysmal movement disorders in families: evidence for shared
      mechanisms.
AB  - The epilepsies have been regarded as clinically distinct from the paroxysmal
      movement disorders. Recently, a variety of ion channel defects have been
      identified as the biological basis of certain familial epilepsies and paroxysmal
      movement disorders. We studied two families with the co-occurrence of epilepsy,
      movement disorders and migraine. Information was obtained on 147 individuals in
      the two families. In family WF, there was a co-occurrence of epilepsy (benign
      infantile convulsions, idiopathic generalized epilepsy), episodic ataxia (with
      cerebellar atrophy and without myokymia) and common migraine. In family CL,
      epilepsy (febrile seizures, febrile seizures plus), kinesigenic paroxysmal
      dyskinesia and migraine (including hemiplegic migraine) were observed in various
      combinations over 3 generations. The observations in these two families, together
      with review of the literature, suggest that the co-occurrence of epilepsy
      (particularly benign infantile convulsions), paroxysmal movement disorders and
      migraine is not due to chance. Thus, these distinct clinical phenomena could have
      a shared biological basis and ion channel defects are an attractive possibility.

PMID- 10937139
TI  - Video-EEG telemetry: apparent manifestation of both epileptic and non-epileptic
      attacks causing potential diagnostic pitfalls.
AB  - Video-EEG telemetry is often used to support the diagnosis of non-epileptic
      seizures (NES). Although rare, some patients may have both epileptic seizures
      (ES) and NES. It is crucially important to identify such patients to avoid the
      hazards of inappropriate anticonvulsant withdrawal. To delineate the
      electroclinical characteristics and diagnostic problems in this group of
      patients, we studied the clinical, EEG and MRI features of 14 consecutive
      patients in whom separate attacks, considered to be both NES and ES were recorded
      using video-EEG telemetry. Only two patients were drug-reduced during the
      telemetry. Most patients had their first seizure (ES or NES) in childhood (median
      age 7 years; range: 6 months-24 years); 8/14 patients were female. Brain MRI was
      abnormal in 10/14 patients. Interictal EEG abnormalities were present in all
      patients; 13/14 had epileptiform and 1/14 only background abnormalities. Over 70
      seizures were recorded in these 14 patients: in 12/14 patients, the first
      recorded seizure was a NES (p < 0.001), and 7 of these patients had at least one
      more NES before an ES was recorded. Only 3/14 patients had more than 5 NES before
      an ES was recorded. Recording a small number of apparently NES in an individual
      by no means precludes the possibility of additional epilepsy. Particular care
      should be taken, and multiple (> 5) seizure recording may be advisable, in
      patients with a young age of seizure onset, interictal EEG abnormalities, or a
      clear, potential aetiology for epilepsy.

PMID- 10937140
TI  - Basal ganglia involvement in rotational seizures.
AB  - Body rotation during partial epileptic seizures remains a poorly understood
      clinical feature, possibly related to the ictal involvement of specific cortical
      areas (e.g. vestibular cortex). However, there are both experimental and clinical
      arguments which support the hypothesis of basal ganglia asymmetric activation
      during such complex motor behavior. We report a patient exhibiting rotational
      seizures which proved to arise from right anterior temporal lobe structures and
      the orbito-cingular cortex, as demonstrated during stereotactic EEG recordings.
      An ictal 99mTc-ECD-SPECT study was performed during an electrically induced
      seizure, similar to the seizures usually experienced by the patient but without a
      rotatory component, showing a marked increase of cerebral blood flow in the
      lenticular nucleus, ipsilaterally to the epileptogenic area. This finding
      suggests that lenticulate involvement might be necessary to produce an ictal
      circling behavior. As circling behavior can be observed during epileptic seizures
      originating from areas widely distributed in the cortex, one may postulate that
      the basal ganglia involvement is the "final common pathway" underlying the
      rotational part of the clinical symptomatology.

PMID- 10937141
TI  - Tactile evoked spikes in children.
AB  - Tactile evoked spikes (TES) are a well known EEG feature in children. We reviewed
      our previous studies concerning this phenomenon, with special reference to the
      influence of sleep and stimulation rate, the relation with middle-long latency
      somatosensory evoked potentials (MLSEP) and the relation between TES and
      spontaneous spikes in the same individual. New data were obtained by re
      evaluating 566 children with TES, by assessing MLSEP from each finger, in 15
      subjects with TES, and by studying MLSEP following posterior tibial nerve
      stimulation in 12 children with TES. TES appear to be enlarged components of
      MLSEP which are present in some children aged 4 to 14 years; they tend to
      increase during NREM sleep and to decrease during REM sleep; Their amplitude
      decreases at stimulation rates above 3 Hz. TES are associated with an increased
      risk of epileptic seizures, which usually have a benign prognosis. The possible
      neurophysiological mechanisms underlying this phenomenon are discussed.

PMID- 10937142
TI  - Hemifacial spasm or subcortical epilepsy?
AB  - A child with Goldenhar's syndrome presented at about one week of age with
      stereotyped, repetitive paroxysmal episodes of hemifacial contraction, suggestive
      of partial seizures or hemifacial spasm. Later in life he also developed
      independent, permanent abnormal eye and chin movements identical in rhythm to
      those seen in myorhythmias, suggesting involvement of the dentato-olivary
      pathway. MRI demonstrated a hamartomatous lesion at the level of the
      pontomedullary junction. We speculate that the nature of the lesion could be
      responsible for the partial seizures mimicking hemifacial spasm and that because
      of its location, this same lesion could also be implicated in the genesis of
      myorhythmias. The presence of a hamartomatous lesion in a region affected by the
      abnormal development of the first and second branchial arches is not fortuitous.

PMID- 10937143
TI  - Seizure with prominent tonic initial signs followed by psychomotor features: a
      case report clinically manifesting an unusual ictal evolution.
AB  - A clinically tonic seizure phase, immediately followed by psychomotor features
      (right hand dystonic posture, left hand and oral automatisms), was recorded by
      video and EEG, in a patient who had gliosis of the left temporal lobe and left
      hippocampal atrophy. Interictal epileptiform discharges were frequently seen in
      the left temporal area, and at the time of the tonic seizure phase, ictal spike
      discharges were continuously observed at the left posterior temporal area, which
      was recognized only by applying a high frequency filter (HFF) of 15 Hz to the
      digitally recorded EEG because EMG artifacts totally obscured the EEG with a HFF
      of 60 Hz. It is most likely that tonic seizure can occur in an adult patient with
      temporal lobe epilepsy, and it is speculated that an epileptogenic focus might
      activate a certain brain area which is regarded as a symptomatogenic zone for
      tonic seizures. If the tonic seizure phase is immediately followed by psychomotor
      features as seen in the present patient, the former could be due to focal
      epilepsy.

PMID- 10937144
TI  - Focal seizures versus focal epilepsy in infancy: a challenging distinction.

PMID- 10937145
TI  - Benign epileptic seizures in infancy followed by paroxysmal choreo-athetosis
      during adolescence.

PMID- 10937146
TI  - Pediatric epilepsy surgery: the widening spectrum of surgical candidacy.

PMID- 10937147
TI  - Effects of valproate, vigabatrin and tiagabine on GABA uptake into human
      astrocytes cultured from foetal and adult brain tissue.
AB  - The antiepileptic agents sodium valproate (VPA), vigabatrin (VGB) and tiagabine
      (TGB) have been proposed to exert their effects, at least in part, by an action
      on the transport of the inhibitory neurotransmitter gamma-aminobutyric acid
      (GABA). This information has, however, been gleaned from studies employing
      experimental systems derived from animal tissues. We have conducted preliminary
      studies of the effects of VPA, VGB and TGB on the transport of GABA into primary
      cultures of human astrocytes, derived from both adult and foetal tissues.
      Astrocytes were prepared from cerebral cortical tissue obtained from patients
      undergoing surgery for intractable epilepsy, and from spontaneously aborted
      foetuses (16-24 weeks gestation). The cells were isolated via a series of
      enzymatic digestions, grown under standard culture conditions for around 21 days
      and then assayed for GABA uptake activity. VPA (1,000 microM), VGB (100 microM)
      and TGB (200 nM) all significantly (p < 0.05) reduced the uptake of GABA into
      primary cultures of human adult astrocytes following a one hour exposure. VPA
      (1,000 microM) and VGB (100 microM) similarly reduced GABA uptake into astrocytes
      derived from human foetal tissue, while TGB (200 and 500 nM) was without effect.
      The results of these preliminary studies suggest that VPA and VGB reduce GABA
      transport into both adult- and foetally-derived human astrocytes, whereas TGB
      appears active only in cells cultured from adult brain. Delayed development of
      the GAT-1 transporter in foetal tissue could explain this observation.

PMID- 10937148
TI  - Efficacy of lamotrigine in idiopathic generalized epilepsy syndromes: a video-EEG
      controlled, open study.
AB  - PURPOSE: This prospective, open, video-EEG-controlled study examined the efficacy
      of lamotrigine (LTG) as add-on and monotherapy in idiopathic generalized epilepsy
      (IGE). METHODS: 47 patients received LTG either because of insufficient seizure
      control (n = 35) or serious side effects of prior antiepileptic drugs (AED). Long
      term video-EEG recordings were performed before and after the introduction of
      LTG. The mean follow-up time was 25.5 months. RESULTS: Of 12 patients with
      refractory childhood absence epilepsy, 9 became seizure free; in one child with
      absences with eyelid myoclonia, absence frequency was reduced > 50%; in 2
      children with absences with a mild atonic component, seizure reduction was only
      transient. Of 12 patients with juvenile absence epilepsy, 10 became seizure-free
      and, in 2, a > 50% reduction was obtained. In 15 patients with juvenile myoclonic
      epilepsy, complete seizure control was achieved in 7 patients, in 6 patients
      myoclonia persisted. In one patient generalized tonic-clonic seizures also
      persisted and another patient developed a rash, LTG was therefore stopped. Of 5
      patients with grand-mal on awakening, 3 became seizure-free, and a reduction of >
      50% was obtained in one patient; LTG was stopped in one patient because of poor
      compliance. Three patients with pure photosensitive epilepsy became seizure-free.
      At the end of the study, 11 patients were seizure-free on LTG monotherapy, and in
      most other patients concomitant AED dosage could be substantially reduced.
      CONCLUSIONS: Lamotrigine was effective and well tolerated in patients with
      various IGE syndromes, although differences were observed between individual
      syndromes and seizure types.

PMID- 10937150
TI  - Somatosensory evoked potentials and EEG findings in siblings of juvenile
      myoclonic epilepsy patients.
AB  - PURPOSE: In order to demonstrate cortical hyperexitability and to determine the
      efficacy of 'SEP of high amplitude (HASEP) in detecting asymptomatic relatives of
      JME patients, we evaluated the EEG findings and SEP in asymptomatic siblings of
      JME patients. METHODS: We analysed the EEG and SEP findings of 37 JME patients
      and 48 asymptomatic siblings of 27 patients and compared the results with healthy
      volunteers. RESULTS: Of 13 asymptomatic siblings with EEG abnormalities (27.1%),
      5 had 4-6 Hz spike/polyspike and wave paroxysms (10.4%), 5 had slow wave
      paroxysms (10.4%), and the remaining 3 patients exhibited focal spike and wave
      activity during hyperventilation (6.25%). No significant difference was found
      between JME patients, asymptomatic siblings and control groups with respect to
      N20 latencies. N20/P25 amplitudes were significantly higher in both JME group and
      asymptomatic siblings than those of control cases. HASEP were observed in 8 out
      of 37 JME patients (21.6%), 10 out of 48 healthy siblings (20.8%) and none of the
      control cases. The consanguinity rate was higher in parents of patients who had
      at least one asymptomatic sibling with EEG and/or SEP abnormalities (68.7%) than
      in those of patients who had siblings with no EEG and SEP abnormalities (9.9%).
      We suggest that the high rate of SEP and EEG changes among offspring of
      consanguineous marriages might reflect the genetic heterogeneity of the disease.

PMID- 10937149
TI  - Reading epilepsy in a patient with previous idiopathic focal epilepsy with
      centrotemporal spikes.
AB  - RATIONALE: Reading epilepsy (RE) is a form of reflex epilepsy currently
      classified as an idiopathic localization-related epilepsy (ILAE, 1989). METHODS:
      We describe a 30 year-old right-handed male who suffered since the age of 8 from
      nocturnal partial motor seizures. Clinical features were typical of BECT. We
      reviewed the EEG recorded at that time which showed centrotemporal spike and
      waves. He was seizure-free from the age of 12 to the age of 17 when seizures
      evoked only by reading appeared. No other stimuli provoked seizures. Neurological
      and neuroradiological (CT and MR) investigations were normal. Baseline video
      polygraphic EEG recordings were normal while reading aloud provoked myoclonic
      jerks in the facial muscles related to bilateral spike and wave discharges.
      Therapy with carbamazepine and valproic acid strongly reduced seizure frequency.
      CONCLUSION: Recent papers have debated the difficulties in classifying RE among
      the generalized or focal syndromes. Literature reports describe an association
      with RE and juvenile myoclonic epilepsy, supporting the hypothesis of an
      idiopathic generalized form. We report the first documented case with a clear-cut
      idiopathic localization-related epilepsy evolving to a primary reading epilepsy.

PMID- 10937151
TI  - Psychosocial functioning in chronic epilepsy: relation to hippocampal volume and
      histopathological findings.
AB  - MRI volumetric measurements of the ipsi- and contralateral hippocampal volume
      (HV) were performed in a group of 37 patients with lesional and non-lesional
      temporal (TLE), and extratemporal lobe (ETLE) lobe epilepsy. Twenty-six patients
      underwent surgery and the resected tissues subjected to histopathological
      examination. Psychosocial scores were calculated on the basis of employment,
      partnership/family status and presence of a positive psychiatric history. Poorest
      values were obtained for the group with right lesional and non-lesional TLE
      (RTLE, p < 0.001). In this group, significant positive correlations between
      psychosocial functioning and the left hippocampal volume or age of onset were
      observed. We found that the left hippocampal volume in RTLE was smaller with
      increasing epilepsy duration. We conclude that patients with RTLE represent a
      particular group with regard to the structural and psychosocial consequences of
      chronic epilepsy. With regard to histopathological analysis, no particular type
      of lesion was identified as the major determinant of the results described above.

PMID- 10937152
TI  - Paroxysmal non-kinesigenic dyskinesia: pathophysiological investigations.
AB  - The paroxysmal dyskinesias constitute a heterogeneous group of disorders whose
      pathophysiologies and nosologies are still generally unknown. In a boy with
      severe, paroxysmal non-kinesigenic dyskinesia (PNKD), an invasive video
      electrographic study demonstrated that his PNKD did not originate from the
      cortex, while a discharge was registered from the caudate nuclei. An 18FDG PET
      scan failed to show metabolic anomalies. A 18FDOPA and a 11C raclopride PET scans
      revealed a marked reduction in the density of presynaptic dopa decarboxylase
      activity in the striatum, together with an increased density of postsynaptic
      dopamine D2 receptors. These findings may suggest a chronic upregulation of
      postsynaptic dopa receptors, either because of an increase in their numbers or
      changes in their affinity. It remains unknown if these are secondary to reduced
      dopamine synthesis or altered release, or if the changes in striatal dopamine
      receptor binding are a primary or a compensatory mechanism.

PMID- 10937153
TI  - Ipsilateral blinking: a rare lateralizing seizure phenomenon in temporal lobe
      epilepsy.

PMID- 10937154
TI  - SPECT findings in reflex seizures induced by movement in non-ketotic
      hyperglycemia.

PMID- 10937155
TI  - Visual phenomena and headache in occipital epilepsy: a review, a systematic study
      and differentiation from migraine.
AB  - This is a systematic-prospective study of occipital seizures with elementary
      visual hallucinations in 18 patients with symptomatic occipital epilepsy.
      Qualitative and chronological analysis showed that visual seizures usually lasted
      for seconds to 1-3 minutes. Three patients also had longer visual seizures of 20
      150 minutes. Elementary visual hallucinations mainly consisted of coloured and
      small circular patterns flashing or multiplying in a temporal hemifield. Flashing
      lights or non-circular patterns were rare. Three patients experienced achromatic
      flickering lights. None of the patients had the over 4 minute, linear, zigzag,
      and achromatic or black and white patterns characteristic of migraine visual
      aura. Blurring of vision could precede visual hallucinations. Visual seizures
      were usually frequent, often occurring in multiple clusters daily or weekly. They
      usually occurred alone but they often advanced to other occipital and extra
      occipital ictal symptoms. In 7 patients they progressed to temporal lobe seizure
      manifestations, and in 6 to motor partial seizures or ipsilateral
      hemiconvulsions. All but 2 had secondary generalised tonic clonic convulsions.
      Ictal blindness ab initio occurred in 2 and ictal, mainly orbital headache in
      another 2 patients. One patient had ictal vomiting as an occasional symptom.
      Postictal headache, often severe and indistinguishable from migraine, occurred in
      two thirds of the patients, even after brief visual seizures without convulsions.
      Despite relevant structural lesions in brain imaging, 10 patients had a normal
      mental and neurological state. In 8 patients, EEG was also normal or nonspecific.
      Misdiagnosis of visual seizures as visual aura of migraine was common and 3
      patients were misdiagnosed as suffering from migraine. The differential diagnosis
      between migraine and the occipital epilepsies is reviewed. It is concluded that
      elementary visual hallucinations, blindness or both, alone or followed by
      headache and vomiting of symptomatic occipital epilepsy are identical to those of
      idiopathic occipital epilepsy. Progress to temporal lobe structures is different
      and consistent with symptomatic occipital lobe epilepsy. The clinical diagnosis
      of visual seizures is easy if individual elements of duration, colour, shape,
      size, location, movement, speed of development and progress are identified. They
      are markedly different from visual aura of migraine, although they often trigger
      migrainous headache, probably by activating trigeminovascular or brain stem
      mechanisms.

PMID- 10937156
TI  - Can protrusion of the tongue stop seizures in Rolandic epilepsy?
AB  - We report the case of a child with benign partial epilepsy with centro-temporal
      spikes (BECT) in whom protrusion of the tongue stopped the interictal
      abnormalities, and describe the polygraphic EEG recording of a seizure which
      terminated upon voluntary protrusion of the tongue. We mention the close link
      between the post-central (somatosensory) cortex and pre-central (motor) cortex,
      and how the primary sensory area has direct access to the motor cortex. We also
      examine how a tactile stimulus may provoke the inhibition of an epileptic
      discharge.

PMID- 10937157
TI  - Gelastic seizures: video-EEG and scintigraphic analysis of a case with a frontal
      focus; review of the literature and pathophysiological hypotheses.
AB  - We report scalp EEG and SPECT findings in a young patient who experienced
      gelastic seizures; clinical, EEG and scintigraphic data strongly suggested a
      frontal focus in a context of cryptogenic epilepsy. Few cases of gelastic
      seizures originating in the frontal lobe have been reported in the literature,
      most of them involving a diencephalic hamartoma or a temporal focus although, no
      clinical pattern has been found to be specific for each of these three anatomical
      regions. The ictal laughter is of variable nature, unmotivated or associated with
      feelings of mirth, forced or natural, except in the case of a frontal focus where
      the laughter seems consistently described as forced and unmotivated. However,
      mirth and laughter are two dissociable clinical elements; their genesis probably
      involves distinct mechanisms. Anatomical considerations lead to several
      hypotheses concerning laughter generation: it could be a simple reactional
      behavior in response to a modified cognitive process, an automatic behavior or a
      forced action. In a few cases with a temporal focus, laughter seems directly
      related to a disorganization of the associative temporal cortex and may be
      considered as a reactional behavior. In cases with frontal focus, anterior
      cingulate and orbital structures would be particularly implicated in laughter
      genesis, although with possible different pathophysiological routes: in the first
      case by disconnection within the premotor mesial system or by an imbalance
      between premotor mesial and premotor lateral systems, and in the second case by
      activation of a previously conditioned orbital region.

PMID- 10937158
TI  - Exceptionally long absence status: multifactorial etiology, drug interactions and
      complications.
AB  - To our knowledge, petit mal status lasting longer than 2-3 days has been
      documented only once [1]. We report a 66 year-old man with well-documented,
      idiopathic generalized epilepsy who developed petit mal status lasting 6 weeks.
      Valproate levels remained low because of interactions with phenytoin. When
      phenytoin was discontinued, valproate levels increased, and he progressively
      improved. Chronic ischemic changes in the white matter may have been an
      additional factor in the causation and, most likely, in the duration of his
      status. Exceptionally long status and stupor increase the risk of medical
      complications. Valproate remains the medication of choice for the treatment of
      petit mal status. Despite the extraordinary course in this patient, complete
      recovery took place, confirming the benign nature of even such a prolonged
      episode.

PMID- 10937160
TI  - Non-convulsive status in the ring chromosome 20 syndrome: a video illustration of
      3 cases.
AB  - We report the clinical history and the video-EEG recordings of three young adults
      with r(20), who exhibited repeated episodes of non-convulsive status epilepticus,
      often triggered by emotional events. This recognizable clinical entity associates
      a slight mental deficiency, behavioural disorder and epilepsy, often resistant to
      treatment and with a particular clinical presentation. We demonstrate with video
      EEG recording, atypical absence status triggered by emotional behaviour with
      ictal EEG characterized by bifrontal slow waves, often rhythmic, or sharp waves.
      Our report highlights the characteristic features of non-convulsive status in
      this electro-clinical syndrome.

PMID- 10937159
TI  - Rotatory seizures in a patient with tuberous sclerosis.
AB  - We present an 11-year-old girl with tuberous sclerosis who developed seizures
      characterized by circling behavior. Rotatory seizures are uncommon and occur
      mainly secondary to a focal pathology. Our patient had a right temporal epileptic
      focus, confirmed by magnetic resonance imaging (MRI) to be a subcortical lesion
      in the right temporal region. This case is probably the first reported case of
      tuberous sclerosis associated with rotatory seizures with an ictal EEG.

PMID- 10937161
TI  - Evolution of epilepsy surgery in childhood: the neurologist's point of view.
AB  - Surgical treatment of epilepsy in children has been slow to develop because of
      uncertainties regarding the prognosis of early epilepsies, difficulties in the
      diagnosis of causal lesions, the frequency of severe, extensive brain damage, and
      technical problems. Surgery for epilepsy in infants and children raises problems
      quite different from those in adults. This applies especially to severe infantile
      epilepsies for which the aim of treatment may be more to facilitate
      neurodevelopment than to control the seizures. In addition, intractability cannot
      be defined in the same terms at different ages, the time scale being usually much
      shorter in young children and the operations required often extensive. The
      results of surgery in childhood are comparable to those in adults. However,
      indications for surgery and assessment of its results in catastrophic epilepsies
      of infants requires different rules to those that apply to adults and older
      children.

PMID- 10937162
TI  - When is imaging enough?
AB  - Despite tremendous recent advances in both structural and functional
      neuroimaging, these tests alone are not enough to recommend surgery for medically
      refractory epilepsy. A detailed history, careful description of the ictal events,
      and the neurological examination will always be necessary. Interictal EEG and
      neuropsychological testing also add important information. In many situations,
      however, video-EEG monitoring of habitual seizures now plays a confirmatory,
      rather than a primary, role in the presurgical evaluation, and can occasionally
      contribute confounding data that delay or prevent surgical intervention. In the
      present climate of cost-containment, it is reasonable to ask if this expensive
      diagnostic tool is always needed when it is clear by other means that seizures
      are not psychogenic, particularly in certain pediatric surgically remediably
      syndromes such as those catastrophic epilepsys of infants and young children
      amenable to hemispherectomy, and drop attack that can be treated with corpus
      callosotomy, as well as mesial temporal lobe epilepsy and seizures due to
      discrete resectable lesions that often become medically intractable in
      adolescence. Retrospective studies should be carried out to determine when long
      term, in-patient, video-EEG monitoring in these conditions add information that
      appropriately changes the therapeutic approach.

PMID- 10937163
TI  - Research perspectives in cortical dysplasia and associated epilepsies.
AB  - Our understanding of cortical alterations and related epilepsies has grown
      enormously in the last decade thanks to the explosion of basic information from
      laboratory neuroscience combined with advances in diagnostic tools, therapeutic
      approaches and surgical techniques. In the present paper, we briefly review the
      most important advances in these fields from the point of view of the clinician
      concerned with cortical malformation-related epilepsies. We propose that a highly
      effective way forward, expected not only to widen knowledge of the basic
      mechanisms of seizure generation, but also to improved the management of
      patients, would be to promote interdisciplinary research programmes on resected
      human cortex that involve neurosurgeons, neurologists and laboratory
      neuroscientists.

PMID- 10937164
TI  - Catastrophic epilepsy in infants and children: identification of surgical
      candidates.
AB  - Some pediatric candidates for epilepsy surgery have epilepsy which is considered
      catastrophic because of a high seizure frequency, often many per day, in
      association with developmental stagnation or regression. Increasing numbers of
      infants with catastrophic epilepsy are being considered for surgical treatment,
      if they have the key elements of surgical candidacy including medically
      intractable epilepsy, a localized epileptogenic zone, and a low risk of new,
      unacceptable, postoperative neurologic deficits. Most of these infants have had
      low grade tumor, cortical development malformations, or other epileptogenic
      lesions visualized on preoperative MRI. The assessment of potential risks and
      benefits for surgery in these patients involves complex, age-related issues
      including the possible impact of uncontrolled seizures or surgery, on cognitive
      development. This review will address some of these issues in the context of two
      clinical cases.

PMID- 10937165
TI  - Neuropsychology of childhood epilepsy: pre- and postsurgical assessment.
AB  - Childhood epilepsy is one of the most prevalent forms of chronic and disabling
      childhood disorders. Because it disrupts brain maturation, it has long been
      thought to produce non-specific consequences such as mental deficiency and
      behavioral problems. However, advances in medical knowledge have shown that
      childhood epilepsy should not be considered as a single disorder, and it is now
      becoming apparent that various clinical entities have different cognitive
      expressions that yet need to be specified. The purpose of this paper is to
      provide an up-to-date analysis of this multi-faceted pathology. The first section
      is devoted to the characterization of the neuropsychological profile that
      accompanies focal epilepsies, as defined by the site of the epileptic process. We
      report the first group study of children with frontal lobe epilepsy. The results
      indicate that frontal lobe epilepsy produces symptoms (deficits of planning,
      attention and motor dexterity) that are akin to those found in frontal-lesioned
      adults. Similarly, like in adults, temporal lobe epilepsy produces memory
      impairment in children as well as behavioral and academic disturbances. Occipito
      parietal lobe epilepsy is rare in children and its effects still need to be
      specified. The second section deals with the neuropsychological techniques used
      in presurgical evaluation. Finally, the various neurosurgical procedures that are
      increasingly being used as part of the arsenal of epilepsy treatment are
      described along with the neuropsychological findings that are associated with
      these interventions. It can be concluded that the beneficial effects of epilepsy
      surgery (callosotomy, hemispherectomy, temporal and extra-temporal resections) by
      far outweigh the few cognitive deficits that are occasionally reported following
      these interventions.

PMID- 10937166
TI  - Nocturnal paroxysmal dystonia due to a subfrontal cortical dysplasia.
AB  - The nature and nosology of nocturnal paroxysmal dystonia (NPD) have been
      controversial. Some authors consider it as a type of parasomnia, akin to night
      terrors and the official Classification of Sleep Disorder includes NPD within the
      parasomnias [1]. Others have opened for its epileptic nature, although mainly on
      circumstantial evidence. The location of the epileptogenic area has been so far
      unknown. A child with NPD was studied extensively, and in spite of normal scalp
      EEGs, all of his attacks were shown to originate from his right orbitofrontal
      cortex. Surgical ablation of an unsuspected cortical dysplastic lesion led to
      full control.

PMID- 10937167
TI  - "Dual pathology" and the significance of surgical outcome in "Dostoewsky's
      epilepsy".
AB  - A patient with a right occipital arterio-venous malformation (AVM) and seizures
      heralded by "lights", and experiencing "ecstasy" underwent a right occipital
      lobectomy after the AVM was embolized. Thereafter, seizures began with motor
      arrest and lip smacking, but never again with "light and ecstasy". A right
      temporal lobectomy and electrocorticogram (E.Co.G) were performed under local
      anesthesia four years after occipital lobectomy. Abundant spiking activity was
      recorded from the right hippocampus which showed gliosis and neuronal loss in the
      pathology studies. Electrical stimulation of the lateral and basal temporal
      cortices failed to elicit the vision of "lights" or the experience of "ecstasy".
      The patient has had two seizures in the last two years as a result of a lapse in
      taking his anti-convulsant medication. He now lives alone, seizure-free. The
      possible abnormally induced functional network organization and structures
      involved in the production of the "ecstasy" phenomenon are discussed.

PMID- 10937168
TI  - Is it juvenile myoclonic epilepsy?
AB  - A 21-year old man with marked developmental delay was referred for the diagnosis
      of myoclonic jerks (MJ), which were sometimes responsible for sudden falls
      without loss of consciousness, that had begun 2 years before, and for a recent
      generalized tonic-clonic seizure preceded by a cluster of MJ. Physical
      examination revealed a small stature, bilateral pyramidal signs, severe mental
      retardation, and retinis pigmentosa. Etiological factors for this encephalopathy
      were not found (muscle and skin biopsies, karyotype and extensive blood
      chemistry). Waking interictal EEG showed a normal background activity and
      generalized poly-spike-and wave (PSW) discharges. Photic stimulation disclosed a
      marked photoparoxysmal response, sometimes associated with myoclonic jerks. Three
      spontaneous jerks accompanied by a burst of generalized PSW were recorded on
      awakening from a nap. The MRI disclosed wide ventricles, a thin corpus callosum,
      brainstem atrophy and a so-called "redundant gyration"; these changes were
      evocative of acquired perinatal damage. Juvenile myoclonic epilepsy (JME) was
      diagnosed and valproate was started resulting in complete control of seizures.
      During a 5-year follow-up, the patient has remained seizure-free and the EEG
      consistently normal. In our opinion, JME can be diagnosed in very uncommon
      settings, including patients with significant brain damage, as long as all the
      other criteria for the diagnosis are present.

PMID- 10937169
TI  - Hypothalamic hamartoma, precocious puberty and gelastic seizures: a special model
      of "epileptic" developmental disorder.
AB  - Based on a review of the literature and a detailed longitudinal single case study
      of a child with early onset gelastic seizures and hypothalamic hamartoma, the
      authors review the arguments suggesting that the acquired cognitive and
      behavioral symptoms seen in the majority of cases of this special epileptic
      syndrome result from a direct effect of the seizures. The early neurobehavioral
      profile of the case presented in this paper and that of a previous study is
      particular and combines features of a pervasive developmental and an attention
      deficit disorder which are probably closely related to the particular location of
      the epilepsy and its spread from the hypothalamus.

PMID- 10937170
TI  - Carbamazepine-induced combined phonic and motor tic in a boy with Down's
      syndrome.
AB  - We report the occurrence of a tic in a boy with Down's syndrome. The movement
      disorder was induced by carbamazepine (CBZ) and resolved completely after
      discontinuation of CBZ. The development of tics seems to be a rare, idiosyncratic
      side effect of CBZ in children.

PMID- 10937172
TI  - Treatment of children with "ordinary" epilepsy.
AB  - Many children with epilepsy have a relatively benign clinical course with
      eventual remission of their seizures and no further need for medication. It is
      not easy to be sure who these children are at the time of diagnosis, but they do
      not have catastrophic epilepsy. Epilepsy is best defined as two unprovoked
      seizures. Not all of these children require treatment and treatment is motivated
      by fear of brain damage, injury, death, kindling of additional seizures, and
      social consequences. None of these fears provides an absolute indication for
      treatment. The decision to start medication should be considered on an individual
      basis. The choice of a first AED is arbitrary with most AEDs having equal
      efficacy. Follow-up schedules have not been well studied. However, there is
      fairly convincing evidence that routine blood and urine screening for toxicity is
      of no benefit, if the child is asymptomatic. Serum drug levels are of little
      clear benefit. Once the child has been seizure-free for 6 months to 12 months, it
      is reasonable to consider stopping medication. Only rarely does seizure control
      fail to return if there are recurrences without medication.

PMID- 10937171
TI  - Ictal SPECT hyperperfusion reflects the activation of the symptomatogenic cortex
      in spontaneous and electrically-induced non-habitual focal epileptic seizures:
      correlation with subdural EEG recordings.
AB  - We report a patient with left temporal lobe epilepsy and a left parietal angioma,
      in whom ictal SPECT showed hyperperfusion in a spontaneous and an electrically
      induced, non-habitual focal seizure. A SPECT investigation during an habitual
      seizure originating in the left temporal lobe showed a left temporal
      hyperperfusion. Electrical stimulation of the parietal cortex adjacent to the
      location of a previously resected angioma using subdural electrodes resulted in a
      non-habitual seizure beginning with a unilateral somatosensory aura. Ictal SPECT
      of this seizure demonstrated contralateral central hyperperfusion. We conclude
      from our findings that ictal SPECT hyperperfusion reflects the activation of
      symptomatogenic cortex, which can be induced by both epileptic discharge and
      electrical stimulation.

PMID- 10937173
TI  - Pediatric epilepsy surgery: state of the art, recent developments and future
      perspectives.

PMID- 10937174
TI  - Electrocorticography.
AB  - Electrocorticography (ECOG), the intra-operative recording of cortical
      potentials, has played an important role in the surgical management of patients
      with medically refractory epilepsy. It has been used 1) to localize the
      epileptogenic tissue; 2) map out cortical functions; and 3) predict the success
      of the surgery. Despite its common use, few studies have been done to prove its
      effectiveness in these areas. The technique used in children for recording ECOG
      is very similar to that used in adults except for the limitations imposed by the
      child's age. Anaesthesia must often be used. Based upon a computerized medical
      literature search, a review of this procedure was done. Pre-resection
      localization, and post-resection prediction of outcome was done for temporal and
      extra-temporal resection, both lesional and nonlesional. Most of the available
      studies were in adult patients. All were retrospective in nature. Evidence for
      the role of pre-resection ECOG in determining the degree of resection felt
      necessary to obtain good clinical outcome was limited. Similarly the post
      resection ECOG predication of surgical outcome was restricted.

PMID- 10937175
TI  - Semiological seizure classification: relevance to pediatric epilepsy.
AB  - The selection of terminology, though seemingly unimportant, can have profound
      effects on our thinking. A seizure classification system based exclusively on
      seizure semiology emphasizes the wide diversity and richness of seizure
      expression. In the field of epilepsy surgery, the use of a seizure classification
      system that emphasizes ictal semiology in an invaluable first step in the precise
      localization of ictal onset. This proves to be particularly true in pediatric
      epilepsy, because seizure semiology is more subtle and difficult to characterize.
      The following article describes a semiological seizure classification and its
      relevance to both pediatric epilepsy surgery and status epilepticus.

PMID- 10937176
TI  - Paroxysmal non-kinesigenic dyskinesia.

PMID- 10937177
TI  - The evolution of genetic canalization under fluctuating selection.
AB  - If the direction of selection changes from generation to generation, the ability
      to respond to selection is maladaptive: the response to selection in one
      generation leads to reduced fitness in the next. Because the response is
      determined by the amount of genetic variance expressed at the phenotypic level,
      rapidly fluctuating selection should favor modifier genes that reduce the
      phenotypic effect of alleles segregating at structural loci underlying the trait.
      Such reduction in phenotypic expression of genetic variation has been named
      "genetic canalization." I support this argument with a series of two- and
      multilocus models with alternating linear selection and Gaussian selection with
      fluctuating optimum. A canalizing modifier gene affects the fitness of its
      carriers in three ways: (1) it reduces the phenotypic consequences of genetic
      response to previous selection; (2) it reduces the genetic response to selection,
      which is manifested as linkage disequilibrium between the modifier and structural
      loci; and (3) it reduces the phenotypic variance. The first two effects reduce
      fitness under directional selection sustained for several generations, but
      improve fitness when the direction of selection has just been reversed. The net
      effect tends to favor a canalizing modifier under rapidly fluctuating selection
      regimes (period of eight generations or less). The third effect improves fitness
      of the modifier allele if the fitness function is convex and reduces it if the
      function is concave. Under fluctuating Gaussian selection, the population is more
      likely to experience the concave portion of the fitness function when selection
      is stronger. Therefore, only weak to moderately strong fluctuating Gaussian
      selection favors genetic canalization. This paper considerably broadens the
      conditions that favor genetic canalization, which so far has only been postulated
      to evolve under long-term stabilizing selection.

PMID- 10937178
TI  - Adaptation and the cost of complexity.
AB  - Adaptation is characterized by the movement of a population toward a many
      character optimum, movement that results in an increase in fitness. Here I
      calculate the rate at which fitness increases during adaptation and describe the
      curve giving fitness versus time as a population approaches an optimum in
      Fisher's model of adaptation. The results identify several factors affecting the
      speed of adaptation. One of the most important is organismal complexity--complex
      organisms adapt more slowly than simple ones when using mutations of the same
      phenotypic size. Thus, as Fisher foresaw, organisms pay a kind of cost of
      complexity. However, the magnitude of this cost is considerably larger than
      Fisher's analysis suggested. Indeed the rate of adaptation declines at least as
      fast as n-1, where n is the number of independent characters or dimensions
      comprising an organism. The present results also suggest that one can define an
      effective number of dimensions characterizing an adapting species.

PMID- 10937179
TI  - Reinforcement and the genetics of nonrandom mating.
AB  - The occurrence of reinforcement is compared when premating isolation is caused by
      the spread of a gene causing females to prefer to mate with males carrying a
      population-specific trait (a "preference" model) and by a gene that causes
      females to prefer to mate with males that share their own trait phenotype (an
      "assortative mating" model). Both two-island models, which have symmetric gene
      flow, and continent-island models, which have one-way gene flow, are explored.
      Reinforcement is found to occur much more easily in a two-island assortative
      mating model than in any of the other three models. This is due primarily to the
      fact that in this model the assortative mating allele will automatically become
      genetically associated in each population with the trait allele that is favored
      by natural selection on that island. In contrast, natural selection on the trait
      both favors and opposes the evolution of premating isolation in the two-island
      preference model, depending on the particular population. These results imply
      that species recognition in the context of mating may evolve particularly easily
      when it targets cues that are favored by natural selection in each population. In
      the continent-island models, reinforcement is found to occur more often under the
      preference model than the assortative mating model, thus reversing the trend from
      the two-island models. Patterns of population subdivision may therefore play a
      role in determining what types of premating isolation may evolve.

PMID- 10937180
TI  - Estimating sexual selection and sexual isolation effects from mating frequencies.
AB  - Sexual selection (defined as the change in genotypic or phenotypic frequencies of
      mated versus total population frequencies) and sexual isolation (defined as the
      deviation from random mating in mated individuals) show different evolutionary
      consequences and partially confounded causes. Traditionally, the cross-product
      estimator has been used to quantify sexual selection, whereas a variety of
      indexes, such as Yule V, Yule Q, YA, joint I, and others have been used to
      quantify sexual isolation. Because the two types of estimators use different
      scales, the effects of both processes cannot be monitored simultaneously. We
      describe three new related statistics that quantify both sexual selection (PSS)
      and sexual isolation (PSI) effects for every mating pair combination in
      polymorphic traits, as well as measure their combined effects (PTI = PSI x PSS).
      The new statistics have the advantage of providing information on every mating
      pair combination, quantifying the effects of sexual selection and isolation in
      the same units, and detecting asymmetry in sexual isolation. The ability of the
      new statistics to ascertain the biological causes of sexual selection and sexual
      isolation are investigated under different models involving distinct marginal
      frequencies, mate propensity, and mate choice coefficients. We also studied the
      use of classical isolation indexes applied on PSI coefficients, instead of on raw
      data. The use of the classical indexes applied to PSI coefficients considerably
      reduces the statistical bias of the estimates, revealing the good estimation
      properties of the new statistics.

PMID- 10937181
TI  - Sex-limited mutations and the evolution of sexual dimorphism.
AB  - Although the developmental and genetic mechanisms underlying sex differences are
      being elucidated in great detail in a number of species, there remains a breach
      between proximate and evolutionary studies of sexual dimorphism. More precisely,
      the evolution of sex-limited gene expression at autosomal loci has not been well
      reasoned using either theoretical or empirical methods. Here, I show that a
      Mendelian genetic model including elementary details of sexual differentiation
      provides novel insight into the evolution of sex differences via sex limitation.
      This model indicates that the nature of allelic effects and the pattern of
      selection must be known in both sexes to predict the evolution of sex
      differences. That is, selection interacts with genetic variation for sexual
      dimorphism to produce unanticipated patterns of trait divergence or convergence
      between the sexes. Ultimately, this model may explain why previous models for the
      evolution of sexual dimorphism do not predict the erratic behavior of the sex
      difference during artificial selection experiments.

PMID- 10937182
TI  - Likelihood analysis of ongoing gene flow and historical association.
AB  - We develop a Monte Carlo-based likelihood method for estimating migration rates
      and population divergence times from data at unlinked loci at which mutation
      rates are sufficiently low that, in the recent past, the effects of mutation can
      be ignored. The method is applicable to restriction fragment length polymorphisms
      (RFLPs) and single nucleotide polymorphisms (SNPs) sampled from a subdivided
      population. The method produces joint maximum-likelihood estimates of the
      migration rate and the time of population divergence, both scaled by population
      size, and provides a framework in which to test either for no ongoing gene flow
      or for population divergence in the distant past. We show the method performs
      well and provides reasonably accurate estimates of parameters even when the
      assumptions under which those estimates are obtained are not completely
      satisfied. Furthermore, we show that, provided that the number of polymorphic
      loci is sufficiently large, there is some power to distinguish between ongoing
      gene flow and historical association as causes of genetic similarity between
      pairs of populations.

PMID- 10937183
TI  - Evolutionary dynamics of pathogen resistance and tolerance.
AB  - Host organisms can respond to the threat of disease either through resistance
      defenses (which inhibit or limit infection) or through tolerance strategies
      (which do not limit infection, but reduce or offset its fitness consequences).
      Here we show that resistance and tolerance can have fundamentally different
      evolutionary outcomes, even when they have equivalent short-term benefit for the
      host. As a gene conferring disease resistance spreads through a population, the
      incidence of infection declines, reducing the fitness advantage of carrying the
      resistance gene. Thus genes conferring complete resistance cannot become fixed
      (i.e., universal) by selection in a host population, and diseases cannot be
      eliminated solely by natural selection for host resistance. By contrast, as a
      gene conferring disease tolerance spreads through a population, disease incidence
      rises, increasing the evolutionary advantage of carrying the tolerance gene.
      Therefore, any tolerance gene that can invade a host population will tend to be
      driven to fixation by selection. As predicted, field studies of diverse plant
      species infected by rust fungi confirm that resistance traits tend to be
      polymorphic and tolerance traits tend to be fixed. These observations suggest a
      new mechanism for the evolution of mutualism from parasitism, and they help to
      explain the ubiquity of disease.

PMID- 10937184
TI  - Evolution of virulence in a heterogeneous host population.
AB  - There is a large body of theoretical studies that investigate factors that affect
      the evolution of virulence, that is parasite-induced host mortality. In these
      studies the host population is assumed to be genetically homogeneous. However,
      many parasites have a broad range of host types they infect, and trade-offs
      between the parasite virulence in different host types may exist. The aim of this
      paper is to study the effect of host heterogeneity on the evolution of parasite
      virulence. By analyzing a simple model that describes the replication of
      different parasite strains in a population of two different host types, we
      determine the optimal level of virulence in both host types and find the
      conditions under which strains that specialize in one host type dominate the
      parasite population. Furthermore, we show that intrahost evolution of the
      parasite during an infection may lead to stable polymorphisms and could introduce
      evolutionary branching in the parasite population.

PMID- 10937185
TI  - Conditions for the evolution of soldier sperm classes.
AB  - There has been wide disagreement as to whether sperm competition among animals
      can produce a soldier class of sperm to fight against other males. Utilizing
      mathematical models, we analyze the appropriate conditions for the evolution and
      maintenance of a soldier sperm class. We conclude that: (1) soldier sperm evolve
      even if one soldier sperm can kill or block less than one competing sperm; (2)
      soldier sperm evolve faster when there is a large variance in the number of
      competing sperm; (3) soldier ratio increases until reproductive sperm are too
      scarce to fertilize all ova or a sperm intensely refuses to become a soldier; and
      (4) soldier sperm are more likely to be smaller than reproductive sperm. Our
      models suggest that the conditions for the evolution of a soldier sperm class are
      not stringent.

PMID- 10937186
TI  - Grazing optimization, nutrient cycling, and spatial heterogeneity of plant
      herbivore interactions: should a palatable plant evolve?
AB  - Can the evolution of plant defense lead to an optimal primary production? In a
      general theoretical model, Loreau (1995) and de Mazancourt et al. (1998, 1999)
      have shown that herbivory could increase primary production up to a moderate rate
      of grazing intensity through recycling of a limiting nutrient, provided several
      conditions are fulfilled. In the present paper, we assume: (1) grazing intensity
      is controlled by plants through their level of palatability; and (2) plant
      fitness is determined by its productivity. We explore the conditions under which
      such an optimal production may be reached through natural selection. We model two
      competing plant types that differ only in palatability and are distributed in a
      patchy landscape determined by the plant-herbivore interaction. Patch size is
      determined by herbivore behavior: herbivores recycle nutrient homogeneously
      within patches, but recycle nutrient proportionally to consumption between
      patches. The model shows that a strategy of intermediate palatability can be
      adaptive in response to a small herbivore that lives on and recycles nutrient
      around one or a few individual plants. For moderately small herbivores, plant
      palatability may evolve towards one of two local convergent strategies, depending
      on the initial conditions. For medium- to large-sized herbivores, the
      nonpalatable strategy is always selected. We discuss the functional and
      evolutionary implications of these results, and suggest that the traditional
      dichotomy describing antagonistic and mutualistic interactions may be misleading.

PMID- 10937187
TI  - Evolution in stressful environments. I. Phenotypic variability, phenotypic
      selection, and response to selection in five distinct environmental stresses.
AB  - Considerable debate has accompanied efforts to integrate the selective impacts of
      environmental stresses into models of life-history evolution. This study was
      designed to determine if different environmental stresses have consistent
      phenotypic effects on life-history characters and whether selection under
      different stresses leads to consistent evolutionary responses. We created
      lineages of a wild mustard (Sinapis arvensis) that were selected for three
      generations under five stress regimes (high boron, high salt, low light, low
      water, or low nutrients) or under near-optimal conditions (control). Full-sibling
      families from the six selection histories were divided among the same six
      experimental treatments. In that test generation, lifetime plant fecundity and
      six phenotypic traits were measured for each plant. Throughout this greenhouse
      study, plants were grown individually and stresses were applied from the early
      seedling stage through senescence. Although all stresses consistently reduced
      lifetime fecundity and most size- and growth-related traits, different stresses
      had contrasting effects on flowering time. On average, stress delayed flowering
      compared to favorable conditions, although plants experiencing low nutrient
      stress flowered earliest and those experiencing low light flowered latest.
      Contrary to expectations of Grime's triangle model of life-history evolution,
      this ruderal species does not respond phenotypically to poor environments by
      flowering earlier. Most stresses enhanced the evolutionary potential of the study
      population. Compared with near-optimal conditions, stresses tended to increase
      the opportunity for selection as well as phenotypic variance, although both of
      these quantities were reduced in some stresses. Rather than favoring traits
      characteristic of stress tolerance, such as slow growth and delayed reproduction,
      phenotypic selection favored stress-avoidance traits: earlier flowering in all
      five stress regimes and faster seedling height growth in three stresses.
      Phenotypic correlations reinforced direct selection on these traits under stress,
      leading to predicted phenotypic change under stress, but no significant selection
      in the control environment. As a result of these factors, selection under stress
      resulted in an evolutionary shift toward earlier flowering. Environmental
      stresses may drive populations of ruderal plant species like S. arvensis toward a
      stress-avoidance strategy, rather than toward stress tolerance. Further studies
      will be needed to determine when selection in stressful environments leads to
      these alternative life-history strategies.

PMID- 10937188
TI  - Phenotypic selection in hawkmoth-pollinated Platanthera bifolia: targets and
      fitness surfaces.
AB  - The present study explored phenotypic selection on phenological and morphological
      reproductive traits in hawkmoth-pollinated Platanthera bifolia (Orchidaceae), a
      Eurasian perennial herb displaying bisexual, long-spurred flowers. The work was
      carried out during three flowering seasons (1993-1995) in a Swedish population.
      Fitness was estimated as the number of pollinia removed (male fitness) and fruits
      produced (female fitness). Targets and patterns of selection were compared
      between years and sex functions by the use of multiple linear regression
      (including correlational selection estimates, i.e., of combination of traits),
      analysis of covariance, and projection pursuit regression (PPR). Results from the
      nonparametric surface-fitting-method PPR showed that selection was mostly linear,
      thus justifying the use of the parametric methods. In all study years, male and
      female fitness were highest in plants with many flowers. This reflects that
      flower number sets an upper limit to fitness and that a large influorescence
      attracts more pollinators. In 1994, the summer was dry and the average spur
      length of P. bifolia was shorter than in the other years. In this year, male and
      female fitness were positively related to spur length, apparently because the
      spur of short-spurred plants was somewhat too short relative to the tongue length
      of the local pollinator for optimal pollen export and import. Additionally, the
      dry weather in 1994 caused a tendency for correlational selection, which was not
      found in the other years of study. Among small individuals (apparently more
      sensitive to drought than large ones), early-flowering plants had higher male and
      female fitness. The results show that patterns of selection may vary both between
      years and between sex functions in perennial hermaphroditic plants. The present
      study is one of the first to consider correlational selection in plants, which
      probably is of common occurrence and deserves to be investigated more.

PMID- 10937189
TI  - Differing selection in alternative competitive environments: shade-avoidance
      responses and germination timing.
AB  - Under competitive conditions, stem elongation in plants is thought to enhance
      fitness by increasing light interception. However, the onset of competition
      should vary with the species of competitor due to interspecific differences in
      timing of emergence and plant growth form. The fitness benefits of elongation may
      therefore depend on the timing of this plastic response. Phenotypic selection
      analyses and path analysis were used to evaluate selection acting on stem
      elongation at early and late life-history stages and the combination of
      germination timing and elongation in an annual plant. Velvetleaf (Abutilon
      theophrasti) were raised in one of three environments experienced by natural
      populations (cornfields; soybean fields; and disturbed, weedy sites). Due to the
      rapid growth rate and high density of plants in disturbed areas, selection to
      increase seedling-stage elongation was expected in weedy sites. Due to the wide
      spacing of crop plants, competition for light is initially low in cultivated
      fields, but intensifies as the season progresses. Selection for increased
      elongation at later nodes was expected in soybean fields because velvetleaf can
      often overtop soy and thereby increase leaf exposure. In contrast, selection
      against late elongation was expected in cornfields because velvetleaf are
      incapable of overtopping corn. Individuals that elongate would experience the
      carbon cost of allocating to structural tissue, but fail to experience a carbon
      return through increased light interception. The phenotypic selection analyses
      were consistent with these predictions and therefore support the role of stem
      elongation as an adaptation to interspecific competition. Selection also acted on
      the combination of germination timing and elongation. In the weedy environment,
      early emergence in conjunction with enhanced stem elongation conveyed the highest
      fitness. Reduced elongation was favored among individuals that emerged late,
      potentially because these individuals were unable to overtop neighbors. The
      results of this study demonstrate that the timing of stem elongation strongly
      affects competitive success. Environments that differ in the timing of
      competition for light select for elongation at different life-history stages, and
      this selection depends on the timing of emergence.

PMID- 10937190
TI  - Frequency and spatial patterning of clonal reproduction in Louisiana iris hybrid
      populations.
AB  - The plant genera in which natural hybridization is most prevalent tend to be
      outcrossing perennials with some mechanism for clonal (i.e., asexual)
      reproduction. Although clonal reproduction in fertile, sexually reproducing
      hybrid populations could have important evolutionary consequences, little
      attention has been paid to quantifying this parameter in such populations. In the
      present study, we examined the frequency and spatial patterning of clonal
      reproduction in two Louisiana iris hybrid populations. Allozyme analysis of both
      populations revealed relatively high levels of genotypic diversity. However, a
      considerable amount of clonality was apparent. Nearly half of all genets (47%) in
      one population and more than half (61%) in the other had multiple ramets.
      Furthermore, both populations exhibited relatively high levels of genetic
      structuring, a pattern that resulted from the aggregation of clonal ramets. The
      occurrence of clonal reproduction in hybrid populations could not only facilitate
      introgression through an increase in the number of flowering ramets per genet
      and/or the survivorship of early generation hybrids, but might also influence the
      mating system of such populations. Any potential increase in the selfing rate due
      to cross-pollination among ramets of the same genet may, in turn, increase the
      likelihood of homoploid hybrid speciation.

PMID- 10937191
TI  - Does evolution of iteroparous and semelparous reproduction call for spatially
      structured systems?
AB  - A persistent question in the evolution of life histories is the fitness trade-off
      between reproducing only once (semelparity) in a lifetime or reproducing repeated
      times in different seasons (iteroparity). The problem can be formulated into a
      research agenda by assuming that one reproductive strategy is resident (has
      already evolved) and by asking whether invasion (evolution) of an alternative
      reproductive strategy is possible. For a spatially nonstructured system, Bulmer
      (1994) derived the relationship v + PA < 1 (PA is adult survival; vbS and bS are
      offspring numbers for iteroparous and semelparous breeding strategies,
      respectively) at which semelparous population cannot be invaded by an iteroparous
      mutant. When the inequality is changed to v + PA > 1, invasion of a semelparous
      mutant is not possible. From the inequalities, it is easy to see that
      possibilities for evolutionary establishment of a novel reproductive strategy are
      rather narrow. We extended the evolutionary scenario into a spatially structured
      system with dispersal linkage among the subunits. In this domain, a rare
      reproductive strategy can easily invade a population dominated by a resident
      reproductive strategy. The parameter space enabling invasion is far more generous
      with spatially structured evolutionary scenarios than in a spatially
      nonstructured system.

PMID- 10937192
TI  - Phenotypic clines, plasticity, and morphological trade-offs in an intertidal
      snail.
AB  - Understanding the genetic and environmental bases of phenotypic variation and how
      they covary on local and broad geographic scales is an important goal of
      evolutionary ecology. Such information can shed light on how organisms adapt to
      different and changing environments and how life-history trade-offs arise.
      Surveys of phenotypic variation in 25 Littorina obtusata populations across an
      approximately 400-km latitudinal gradient in the Gulf of Maine revealed
      pronounced clines. The shells of snails from northern habitats weighed less and
      were thinner and weaker in compression than those of conspecifics from southern
      habitats. In contrast, body size (as measured by soft tissue mass) followed an
      opposite pattern; northern snails weighed more than southern snails. A reciprocal
      transplant between a northern and southern habitat revealed substantial
      plasticity in shell form and body mass and their respective measures of growth.
      Southern snails transplanted to the northern habitat produced lighter, thinner
      shells and more body mass than controls raised in their native habitat. In
      contrast, northern snails transplanted to the southern site produced heavier,
      thicker shells and less body mass than controls raised in their native habitat.
      Patterns of final phenotypic variation for all traits were consistent with
      cogradient variation (i.e., a positive covariance between genetic and
      environmental influences). However, growth in shell traits followed a
      countergradient pattern (i.e., a negative covariance between genetic and
      environmental influences). Interestingly, body growth followed a cogradient
      pattern, which may reflect constraints imposed by cogradient variation in final
      shell size and thickness. This result suggests the existence of potential life
      history trade-offs associated with increased shell production. Differences in L.
      obtusata shell form, body mass, and their respective measures of growth are
      likely induced by geographic differences in both water temperature and the
      abundance of an invading crab predator (Carcinus maenas). Water temperatures
      averaged 6.8 degrees C warmer during the transplant experiment and C. maenas
      abundance is greater in the southern Gulf of Maine. Because both increased water
      temperature and crab effluent affect shell form in the same way, future
      experiments are needed to determine the relative importance of each.
      Nevertheless, it is clear that phenotypic plasticity has an important role in
      producing geographic variation in L. obtusata shell form. Moreover, the evolution
      of phenotypic plasticity in L. obtusata and other marine gastropods may be driven
      by architectural constraints imposed by shell form on body mass and growth.

PMID- 10937193
TI  - Population structure, parasitism, and survivorship of sexual and autodiploid
      parthenogenetic Campeloma limum.
AB  - Two theories for the maintenance of sexual reproduction, the Red Queen hypothesis
      and mutation accumulation, suggest that the dispersal rates of sexuals and
      asexuals may determine the elimination or persistence of asexuals. Under higher
      dispersal rates of asexuals, asexuals may temporarily escape virulent parasites
      and reduce the effects of deleterious mutations. In the present study, I examine
      the population structure, parasite loads, and juvenile survivorship of Campeloma
      limum sexuals and autodiploid parthenogens from the southeastern U.S. Atlantic
      coastal plain. Using mtDNA sequence variation, it is shown that parthenogenetic
      haplotypes with limited sequence divergence are geographically widespread
      throughout this region and there is no significant population differentiation
      over a broad geographical scale. Sexual C. limum populations show significant
      mtDNA differentiation among and within river drainages and there is significant
      isolation by distance. These patterns are consistent with a recent origin and
      range expansion of parthenogens. Prevalence of infection by digenetic trematodes
      is significantly higher in autodiploid parthenogens, and the variance of
      prevalence is also higher in autodiploid parthenogens. I argue that the latter
      pattern indicates that unparasitized parthenogens have temporarily escaped these
      virulent parasites, but recolonization of these populations by trematodes results
      in high infection levels (> 40%), possibly due to reduced variation in resistance
      genes. I also examined whether the survivorship of juvenile sexuals and
      parthenogens varied under different stress levels. Sexual juveniles had twofold
      higher survivorship in all environments. Compared to polyploid parthenogens,
      autodiploid parthenogens may be less buffered against the effects of deleterious
      recessive alleles. I propose that the combined effects of higher parasitism and
      reduced juvenile survivorship of these autodiploid parthenogens accounts for the
      spatial distribution of sexual and parthenogenetic C. limum in the Atlantic
      coastal plain. Parthenogens may persist by higher dispersal rates into marginal
      habitats where there is a temporary escape from digenetic trematodes and
      competition with sexuals.

PMID- 10937194
TI  - Staggered clines in a hybrid zone between two chromosome races of the harvestman
      Gagrellopsis nodulifera (Arachnida: Opiliones).
AB  - We analyzed a hybrid zone between two chromosome races (2n = 16 and 2n = 22) of a
      Japanese harvestman, Gagrellopsis nodulifera Sato and Suzuki (Arachnida:
      Opiliones: Phalangiidae). The hybrid zone is located in the eastern part of
      Tottori Prefecture, western Honshu. The width of the zone is approximately 5 to
      15 km. Three independent tandem fusions/fissions seem to be the main cause of the
      karyotypic differences between the parental races. Ten karyotypic variants were
      found in the hybrid zone. They differed by numbers of diploid chromosomes and
      trivalents detected in meiosis. In most of the collecting sites, karyotypic
      heterozygotes were less common than expected. A positive correlation was found
      between number of trivalents in a karyotype and its deficiency rate. In some
      sites, the deficit of heterozygous individuals was accompanied by an excess of
      the intermediate homozygotes. One of the three transects across the zone was
      studied in detail. We found that three types of single heterozygotes (2n = 17, 2n
      = 19 and 2n = 21) formed a series of successive, spatially separated peaks along
      the transect. Two types of intermediate homozygotes (2n = 18 and 2n = 20) were
      also spatially separated. The most parsimonious explanation of such a structure
      is the staggering of clines of three tandem (or Robertsonian) fusion/fission
      variants that differentiate the parental races caused by selection against
      multiple heterozygotes. Analysis of nondisjunction in single heterozygotes
      demonstrated that there was a strong interindividual variation in nondisjunction
      rate. The mean frequency of aneuploid MII in single heterozygotes was 0.10 +/-
      0.03. Crossover exchanges in some critical regions of trivalents result in
      abnormal chromosomal configurations: chromosomes with unequal chromatids and
      dicentric chromosomes. Frequency of crossover-induced chromosomal abnormalities
      was low in single heterozygotes (approximately equal to 4%), and was unexpectedly
      high in the double heterozygotes (approximately equal to 15%). Selection against
      karyotypic heterozygotes is considered as a main evolutionary force responsible
      for the structuring of the hybrid zone. A positive association between diploid
      chromosome number and altitude was found. The race 2n = 16 tended to occupy lower
      altitudes than the 2n = 22 parental race. Differences in ecological preferences
      may be a result of previous adaptations to different environments in allopatry. A
      hypothesis concerning the origin and evolution of the hybrid zone is proposed.

PMID- 10937195
TI  - Evidence for female mortality in Wolbachia-mediated cytoplasmic incompatibility
      in haplodiploid insects: epidemiologic and evolutionary consequences.
AB  - Until now, only two Wolbachia-mediated cytoplasmic incompatibility (CI) types
      have been described in haplodiploid species, the first in Nasonia (Insect) and
      the second in Tetranychus (Acari). They both induce a male-biased sex ratio in
      the incompatible cross. In Nasonia, CI does not reduce fertility since
      incompatible eggs develop as haploid males, whereas in Tetranychus CI leads to a
      partial mortality of incompatible eggs, thus reducing the fertility of females.
      Here, we study Wolbachia infection in a Drosophila parasitoid, Leptopilina
      heterotoma (Hymenoptera: Figitidae). A survey of Wolbachia infection shows that
      all natural populations tested are totally infected. Crosses between infected
      males and cured females show complete incompatibility: almost no females are
      produced. Moreover, incompatible eggs die early during their development, unlike
      Nasonia. This early death allows the parasitized Drosophila larva to achieve its
      development and to emerge. Thus, uninfected females crossed with infected males
      have reduced offspring production consisting only of males. Evidence of this CI
      type in insects demonstrates that the difference in CI types of Nasonia and
      Tetranychus is not due to specific factors of insects or acari. Using theoretical
      models, we compare the invasion processes of different strategies of Wolbachia:
      CI in diploid species, the two CI types in haplodiploid species, and
      parthenogenesis (the classical effect in haplodiploid species). Models show that
      CI in haplodiploid species is less efficient than in diploid ones. However, the
      Leptopilina type is advantageous compared to the Nasonia type. Parthenogenesis
      may be more or less advantageous, depending on the infection cost and on the
      proportion of fertilized eggs. Finally, we can propose different processes of
      Wolbachia strategy evolution in haplodiploid species from Nasonia CI type to
      Leptopilina CI type or parthenogenesis.

PMID- 10937196
TI  - Latitudinal variation for two enzyme loci and an inversion polymorphism in
      Drosophila melanogaster from Central and South America.
AB  - Many organisms show latitudinal variation for various genetically determined
      traits. Such clines may involve neutral variation and originate from historical
      events or their maintenance may be explained by selection. For Drosophila
      melanogaster, latitudinal variation for allozymes, inversions, and quantitative
      traits has been found on several continents. We sampled D. melanogaster
      populations in Panama and along a transect of 40 latitudinal degrees on the west
      coast of South America. Negative correlations with latitude were found for AdhS
      and alpha GpdhF allele frequencies and for the frequency of the cosmopolitan
      inversion In(2L)t in AdhS alpha GpdhF chromosomes. A positive correlation existed
      between wing length and latitude. Significant correlations were found between
      these traits and climatic variables like temperature and rainfall. The observed
      clines show considerable resemblance to those found on other continents. Gametic
      disequilibrium between AdhS and alpha GpdhF occurred predominantly at higher
      latitudes and was caused by the presence of In(2L)t. The reasons for the clinal
      distributions are discussed and it is argued that selection is the most likely
      explanation. However, the exact nature of the selective force and the
      interactions of allozymes with each other and with In(2L)t are complex and not
      fully understood. In tropical regions In(2L)t-containing genotypes have higher
      fitness than ST/ST and Adh and alpha Gpdh hitchhike with the inversion, but there
      is also evidence for balancing selection at the Adh locus.

PMID- 10937197
TI  - A biogeographic genetic approach for testing the role of reinforcement: the case
      of Drosophila pseudoobscura and D. persimilis.
AB  - The role of reinforcement in speciation can be explained by two distinct models.
      In model I, two diverged populations hybridize and produce fertile hybrids that
      successfully backcross (hybridization with gene flow). In model II, two
      populations hybridize but succeeding backcrosses are unproductive (hybridization
      without gene flow). Using Drosophila persimilis and D. pseudoobscura, we have
      tested model I by comparing the extent of heterospecific introgression in
      sympatric versus allopatric populations. We show that certain expectations of
      this particular model of reinforcement, which is based on hybridization and gene
      flow between divergent populations after secondary contact, are not realized in
      these two species. The evidence consists of the similarity of genetic distances
      as well as proportions of unique/rare alleles between sympatric and allopatric
      heterospecific populations and a negative correlation between genetic distance
      and geographical distance between heterospecific populations, which suggests
      ecological differentiation. This approach in quantifying differential gene flow
      has important consequences to studies that compare sympatric and allopatric
      isolation using genetic distance. Following model I, one would expect a pattern
      of higher prezygotic isolation in sympatric species compared to allopatric
      species of the same genetic distance simply as a result of an underestimation of
      genetic distance due to introgression between sympatric populations. We suggest
      more parsimonious explanations such as reinforcement without genetic exchange
      (model II) and ecological differentiation, which require high levels of
      preexisting reproductive isolation between populations.

PMID- 10937198
TI  - Inbreeding depression and genetic load in laboratory metapopulations of the
      butterfly Bicyclus anynana.
AB  - We investigated the effects of inbreeding on various fitness components and their
      genetic load in laboratory metapopulations of the butterfly Bicyclus anynana. Six
      metapopulations each consisted of four subpopulations with breeding population
      sizes of N = 6 or N = 12 and migration rate of m = 0 or m = 0.33. Metapopulations
      were maintained for seven generations during which coancestries and pedigrees
      were established. Individual inbreeding coefficients at the F7 were calculated
      and ranged between 0.01 and 0.51. Even though considerable purging had occurred
      during inbreeding, the genetic load remained higher than that of many outbreeding
      species: approximately two lethal equivalents were detected for egg sterility,
      one for zygote survival, one for juvenile survival, and one for longevity. Severe
      inbreeding depression occurred after seven generations of inbreeding, which
      jeopardized the metapopulation survival. This finding suggests that the purging
      of genetic load by intentional inbreeding cannot be recommended for the genetic
      conservation of species with a high number of lethal equivalents.

PMID- 10937199
TI  - Barriers to gene flow in Embiotoca jacksoni, a marine fish lacking a pelagic
      larval stage.
AB  - Marine species generally show high dispersal capabilities, which should be
      accompanied by high levels of gene flow and low speciation rates. However,
      studies that focused on the relationship between dispersal and gene flow in
      marine fishes have been inconclusive. This study focuses on the black surfperch,
      Embiotoca jacksoni, a temperate reef fish that lacks a pelagic larval stage and
      lives on almost continuous reefs along the California and Baja California coasts.
      Mitochondrial control-region sequences from 240 individuals were obtained, and
      phylogeographic patterns were analyzed. A major phylogeographic break was found
      at Santa Monica Bay, a sandy expanse that prevents adult dispersal. Deep water
      separating the southern California Channel Islands was also found to be a major
      barrier to gene flow. Minor phylogeographic breaks were also detected in the Big
      Sur/Morro Bay and in the Punta Eugenia/Guerrero Negro regions, but none in the
      Point Conception region. Gene flow levels in E. jacksoni were found to be almost
      identical to those of another species with limited dispersal, Acanthochromis
      polyacanthus, thus indicating that the lack of a pelagic larval stage combined
      with barriers to adult dispersal may have had similar effects on these two
      species.

PMID- 10937200
TI  - Direct and correlated responses to artificial selection on acute thermal stress
      tolerance in a livebearing fish.
AB  - Tradeoffs in performance or fitness across environments have important
      implications regarding the nature of evolutionary constraints. It remains
      controversial whether tradeoffs such as these reflect genetic correlations that
      are genuine evolutionary constraints. However, if such long-term genetic
      constraints do exist, they must be due to underlying pleiotropy such that alleles
      that confer high performance in one environment invariably confer low performance
      in another. The distribution of genetic correlations within and among populations
      can provide insight about the existence of such pleiotropic tradeoffs. The long
      term association of certain teleost fish taxa with particular abiotic
      environments suggests that tradeoffs in performance across environments have
      constrained the geographic distribution of those taxa. Here we report the results
      of an experiment in which we artificially selected on acute heat- and cold-stress
      tolerance in two stocks of the poeciliid fish Heterandria formosa from source
      populations with different thermal histories. Unexpectedly, we observed no direct
      responses to selection. Under certain conditions, fish from the different source
      populations differed significantly in cold tolerance, but not in heat tolerance.
      The results suggest there are no strong pleiotropic tradeoffs between heat- and
      cold-stress tolerance in these populations.

PMID- 10937201
TI  - The dynamics of natural selection and vicariance in the Dominican anole: patterns
      of within-island molecular and morphological divergence.
AB  - The larger islands of the Lesser Antilles are ecologically and geologically
      complex and are inhabited by single, but morphologically variable, Anolis
      species. Although earlier work has indicated that a large part of the
      morphological variation in Anolis oculatus from Dominica can be attributed to
      selection, a history of recurrent volcanic activity over the last few million
      years suggests that vicariance may have also played a significant role. We report
      a study of variation in the cytochrome b gene of mitochondrial DNA across the
      island to address this issue. We uncovered a very high degree of polymorphism,
      with an overall gene diversity of 0.97 and a nucleotide diversity of 0.04.
      Sequences, on average, differ by 3.82% and the maximum pairwise divergence
      (corrected for multiple hits) is 9.29%. Most haplotypes are restricted to single
      localities (a pattern not changed by increasing the sample size). Phylogenetic
      analysis revealed the presence of two distinct lineages on the island with strong
      phylogeographic structure. One of these is geographically restricted to a
      relatively small part of the central Caribbean coast. Sublineages were also
      discernible within the other more widely distributed lineage, but resolution
      within and support for these sublineages was poor. The phylogeographic pattern is
      not congruent with generalized body shape and scalation, but is significantly
      correlated with color pattern. Even when correcting for this lineage effect with
      partial Matrix correspondence tests, the relationship between color pattern and
      vegetation is reaffirmed, suggesting that although both vicariance and selection
      have played a role in the morphological differentiation of this species,
      selection for current environmental conditions has been more important. We
      discuss the causes of the phylogeographic structure in light of the volcanic
      history of the island and highlight the exceptional instance of congruence
      between all morphological character systems and lineage boundaries, which occurs
      at the transition between the northern and southern Caribbean ecotypes.

PMID- 10937202
TI  - The relationship between sexual size dimorphism and habitat use in Greater
      Antillean Anolis lizards.
AB  - Sexual size dimorphism (SSD) is the evolutionary result of selection operating
      differently on the body sizes of males and females. Anolis lizard species of the
      Greater Antilles have been classified into ecomorph classes, largely on the basis
      of their structural habitat (perch height and diameter). We show that the major
      ecomorph classes differ in degree of SSD. At least two SSD classes are supported:
      high SSD (trunk-crown, trunk-ground) and low SSD (trunk, crown-giant, grass-bush,
      twig). Differences cannot be attributed to an allometric increase of SSD with
      body size or to a phylogenetic effect. A third explanation, that selective
      pressures on male and/or female body size vary among habitat types, is examined
      by evaluating expectations from the major relevant kinds of selective pressures.
      Although no one kind of selective pressure produces expectations consistent with
      all of the information, competition with respect to structural habitat and sexual
      selection pressures are more likely possibilities than competition with respect
      to prey size or optimal feeding pressures. The existence of habitat-specific
      sexual dimorphism suggests that adaptation of Anolis species to their environment
      is more complex than previously appreciated.

PMID- 10937203
TI  - Sexual selection drives rapid divergence in bowerbird display traits.
AB  - Sexual selection driving display trait divergence has been suggested as a cause
      of rapid speciation, but there is limited supporting evidence for this from
      natural populations. Where speciation by sexual selection has occurred in newly
      diverged populations, we expect that there will be significant differences in
      female preferences and corresponding male display traits in the absence of
      substantial genetic and other morphological differentiation. Two allopatric
      populations of the Vogelkop bowerbird, Amblyornis inornatus, show large,
      qualitative differences in a suite of display traits including bower structure
      and decorations. We experimentally demonstrate distinct male decoration color
      preferences within each population, provide direct evidence of female preferences
      for divergent decoration and bower traits in the population with more elaborate
      display, and show that there is minimal genetic differentiation between these
      populations. These results support the speciation by sexual selection hypothesis
      and are most consistent with the hypothesis that changes in male display have
      been driven by divergent female choice.

PMID- 10937204
TI  - Matrilineal genetic structure and female-mediated gene flow in red grouse
      (Lagopus lagopus scoticus): an analysis using mitochondrial DNA.
AB  - DNA sequence variation at the hypervariable 5' end of the mitochondrial control
      region was examined in 247 individuals to detect genetic divergence among 14
      populations of red grouse (Lagopus lagopus scoticus) in northeastern Scotland.
      Ten haplotypes were resolved, several of which were shared among populations.
      Analysis of molecular variance, Nei's gamma ST, and a cladistic estimate of the
      amount of gene flow indicated a lack of overall population differentiation.
      Patterns of overall panmixia are in stark contrast to previous reports of
      localized subdivision among the same set of populations detected using
      hypervariable microsatellite markers. Because grouse cocks are territorial and
      show extreme natal philopatry and females are the dispersing sex, such
      discordance could be explained by sex-biased dispersal, with extensive female
      mediated gene flow preventing mitochondrial DNA divergence. However, it is
      difficult to reconcile how effective dispersal of females would not homogenize
      both mitochondrial and nuclear structure simultaneously. We use a model that
      examines the spatial and temporal dynamics of diparentally and uniparentally
      inherited genes to show that, under realistic ecological scenarios and with
      specific differences in the dispersal of males and females, the local effective
      size of the nuclear genome can be less than that of the mitochondrial and the
      patterns of structuring we observe are meaningful.

PMID- 10937205
TI  - Opposing levels of selection can cause neutrality: mating patterns and maternal
      fetal interactions.
AB  - A biallelic viability model based on human data for maternal-fetal interactions
      reported by Hedrick (1997) gives the interesting result of neutral stability at
      all gene frequencies. I show that there are two levels of selection, within and
      among families, acting in opposing directions in this model and that the neutral
      stability occurs when the two levels of selection exactly balance one another, as
      they do in a randomly mating population. Deviations from random mating disrupt
      the balance and consequently destroy the neutral stability. However, with
      inbreeding avoidance, which characterizes the human histocompatibility loci,
      within-family selection is strengthened and among-family selection is weakened.
      This favors the invasion of new alleles and contributes to a high equilibrium
      level of genetic diversity at loci with maternal-fetal interactions affecting
      offspring viability in the pattern described by Hedrick. This pattern of
      selection is remarkably similar to that observed for the maternal effect selfish
      genes, Medea in flour beetles and scat in the mouse, and the Gp-9 gene in the
      fire ant.

PMID- 10937206
TI  - Reproductive effort in viscous populations.
AB  - Here I study a kin selection model of reproductive effort, the allocation of
      resources to fecundity versus survival, in a patch-structured population.
      Breeding females remain in the same patch for life. Offspring have costly,
      partial long-distance dispersal and compete for breeding sites, which become
      vacant upon the death of previous occupants. The main result is that the
      evolutionarily stable reproductive effort decreases as offspring dispersal rate
      increases. The result can be understood as follows: In a well-mixed population
      with global competition, neither adults nor juveniles compete with relatives, but
      in a patch-structured population with dispersal restricted to the juvenile phase,
      juveniles experience relatively less competition with relatives than adults, thus
      making juveniles relatively more valuable. Because this asymmetry between adults
      and juveniles decreases with the dispersal rate, so does the evolutionarily
      stable level of allocation to fecundity.

PMID- 10937207
TI  - Differential migration from high fitness demes in the shining fungus beetle,
      Phalacrus substriatus.
AB  - Using data from three years (1994-1996), I tested whether differential migration
      occurs from demes of high mean fitness in the shining fungus beetle, Phalacrus
      substriatus. The results show evidence for differential migration, thus providing
      evidence from a natural population for a critical demographic assumption of many
      interdemic selection models. To predict the evolutionary response to interdemic
      selection through differential migration, the genetic basis of the variation
      among demes in mean fitness must be known because the observed patterns could
      also be explained by some demes having an intrinsically favorable habitat. Thus,
      the importance of differential migration through interdemic selection in natural
      populations cannot be unequivocally answered without experiments specifically
      addressing the question of what causes differences in mean fitness among demes.

PMID- 10937208
TI  - Evolutionary implications of phenotypic plasticity in the hindlimb of the lizard
      Anolis sagrei.
AB  - Species of Anolis lizards that use broad substrates have long legs, which provide
      enhanced maximal sprint speed, whereas species that use narrow surfaces have
      short legs, which permit careful movements. We raised hatchling A. sagrei in
      terraria provided with only broad or only narrow surfaces. At the end of the
      experiment, lizards in the broad treatment had relatively longer hindlimbs than
      lizards in the narrow treatment. These results indicate that not only is hindlimb
      length a plastic trait in these lizards, but that this plasticity leads to the
      production of phenotypes appropriate to particular environments. Comparison to
      hindlimb lengths of other Anolis species indicates that the range of plasticity
      is limited compared to the diversity shown throughout the anole radiation.
      Nonetheless, this plasticity potentially could have played an important role in
      the early stages of the Caribbean anole radiation.

PMID- 10937209
TI  - Is Wright's shifting balance process important in evolution?

PMID- 10937210
TI  - The ongoing synthesis: a reply to Coyne, Barton, and Turelli.

PMID- 10937211
TI  - Varying migration and deme size and the feasibility of the shifting balance.

PMID- 10937212
TI  - Perspective: sex, recombination, and the efficacy of selection--was Weismann
      right?
AB  - The idea that sex functions to provide variation for natural selection to act
      upon was first advocated by August Weismann and it has dominated much discussion
      on the evolution of sex and recombination since then. The goal of this paper is
      to further extend this hypothesis and to assess its place in a larger body of
      theory on the evolution of sex and recombination. A simple generic model is
      developed to show how fitness variation and covariation interact with selection
      for recombination and illustrate some important implications of the hypothesis:
      (1) the advantage of sex and recombination can accrue both to reproductively
      isolated populations and to modifiers segregating within populations, but the
      former will be much larger than the latter; (2) forces of degradation that are
      correlated across loci within an individual can reduce or reverse selection for
      increased recombination; and (3) crossing-over (which can occur at different
      places in different meioses) will create more variability than having multiple
      chromosomes and so will have more influence on the efficacy of selection. Several
      long-term selection experiments support Weismann's hypothesis, including those
      showing a greater response to selection in populations with higher rates of
      recombination and higher rates of recombination evolving as a correlated response
      to selection for some other character. Weismann's hypothesis is also consistent
      with the sporadic distribution of obligate asexuality, which indicates that
      clones have a higher rate of extinction than sexuals. Weismann's hypothesis is
      then discussed in light of other patterns in the distribution of sexuality versus
      asexuality. To account for variation in the frequency of obligate asexuality in
      different taxa, a simple model is developed in which this frequency is a function
      of three parameters: the rate of clonal origin, the initial fitness of clones
      when they arise, and the rate at which that fitness declines over time. Variation
      in all three parameters is likely to be important in explaining the distribution
      of obligate asexuality. Facultative asexuality also exists, and for this to be
      stable it seems there must be ecological differences between the sexual and
      asexual propagules as well as genetic differences. Finally, the timing of sex in
      cyclical parthenogens is most likely set to minimize the opportunity costs of
      sex. None of these patterns contradict Weismann's hypothesis, but they do show
      that many additional principles unrelated to the function of sex are required to
      fully explain its distribution. Weismann's hypothesis is also consistent with
      what we know about the mechanics and molecular genetics of recombination, in
      particular the tendency for chromatids to recombine with a homolog rather than a
      sister chromatid at meiosis, which is opposite to what they do during mitosis.
      However, molecular genetic studies have shown that cis-acting sites at which
      recombination is initiated are lost by gene conversion as a result, a factor that
      can be expected to affect many fine details in the evolution of recombination. In
      summary, although Weismann's hypothesis must be considered the leading candidate
      for the function of sex and recombination, nevertheless, many additional
      principles are needed to fully account for their evolution.

PMID- 10937213
TI  - A Bayesian framework for the analysis of cospeciation.
AB  - Information on the history of cospeciation and host switching for a group of host
      and parasite species is contained in the DNA sequences sampled from each. Here,
      we develop a Bayesian framework for the analysis of cospeciation. We suggest a
      simple model of host switching by a parasite on a host phylogeny in which host
      switching events are assumed to occur at a constant rate over the entire
      evolutionary history of associated hosts and parasites. The posterior probability
      density of the parameters of the model of host switching are evaluated
      numerically using Markov chain Monte Carlo. In particular, the method generates
      the probability density of the number of host switches and of the host switching
      rate. Moreover, the method provides information on the probability that an event
      of host switching is associated with a particular pair of branches. A Bayesian
      approach has several advantages over other methods for the analysis of
      cospeciation. In particular, it does not assume that the host or parasite
      phylogenies are known without error; many alternative phylogenies are sampled in
      proportion to their probability of being correct.

PMID- 10937214
TI  - Exhaustion of morphologic character states among fossil taxa.
AB  - Frequencies of new character state derivations are analyzed for 56 fossil taxa.
      The hypothesis that new character states are added continuously throughout clade
      history can be rejected for 48 of these clades. Two alternative explanations are
      considered: finite states and ordered states. The former hypothesizes a limited
      number of states available to each character and is tested using rarefaction
      equations. The latter hypothesizes that there are limited possible descendant
      morphologies for any state, even if the character has infinite potential states.
      This is tested using power functions. The finite states hypothesis explains
      states: steps relationships significantly better than does the ordered states
      hypothesis in 14 cases; the converse is true for 14 other cases. Under either
      hypothesis, trilobite clades show appreciably more homoplasty after the same
      numbers of steps than do molluscs, echinoderms, or vertebrates. The prevalence of
      the exhaustion pattern among different taxonomic groups implies that worker
      biases are not to blame and instead implicates biological explanations such as
      intrinsic constraints or persistent selective trends. Regardless of the source of
      increased homoplasy, clades appear to exhaust their available character spaces.
      Nearly all examined taxa show significant increases in proportions of
      incompatible character pairs (i.e., those necessarily implying homoplasy) as
      progressively younger taxa are added to character matrices. Thus, a deterioration
      of hierarchical structure accompanies character state exhaustion. Exhaustion has
      several implications: (1) the basic premise of cladistic analyses (i.e., that
      maximum congruence reflects homology rather than homoplasy) becomes increasingly
      less sound as clades age; (2) sampling high proportions of taxa probably is
      needed for congruence to discern homoplasy from homology; (3) stratigraphic data
      might be necessary to discern congruent homoplasy from congruent homology; and
      (4) in many cases, character states appear to have evolved in ordered patterns.

PMID- 10937215
TI  - Genetic and phylogenetic consequences of island biogeography.
AB  - Island biogeography theory predicts that the number of species on an island
      should increase with island size and decrease with island distance to the
      mainland. These predictions are generally well supported in comparative and
      experimental studies. These ecological, equilibrium predictions arise as a result
      of colonization and extinction processes. Because colonization and extinction are
      also important processes in evolution, we develop methods to test evolutionary
      predictions of island biogeography. We derive a population genetic model of
      island biogeography that incorporates island colonization, migration of
      individuals from the mainland, and extinction of island populations. The model
      provides a means of estimating the rates of migration and extinction from
      population genetic data. This model predicts that within an island population the
      distribution of genetic divergences with respect to the mainland source
      population should be bimodal, with much of the divergence dating to the
      colonization event. Across islands, this model predicts that populations on large
      islands should be on average more genetically divergent from mainland source
      populations than those on small islands. Likewise, populations on distant islands
      should be more divergent than those on close islands. Published observations of a
      larger proportion of endemic species on large and distant islands support these
      predictions.

PMID- 10937216
TI  - Independent contrasts succeed where ancestor reconstruction fails in a known
      bacteriophage phylogeny.
AB  - Methods of ancestor reconstruction are important tools for evolutionary inference
      that are difficult to test empirically because ancestral states are rarely known
      with certainty. We evaluated reconstruction methods for continuous phenotypic
      characters using taxa from an experimentally generated bacteriophage phylogeny.
      Except for one slowly evolving character, the estimated ancestral states of
      continuous phenotypic characters were highly inaccurate and biased, even when
      including a known ancestor at the root. This error was caused by a directional
      trend in character evolution and by rapid rates of character evolution. Computer
      simulations confirmed that such factors affect reconstruction of continuous
      characters in general. We also used phenotypic viral characters to evaluate two
      methods that attempt to estimate the correlation between characters during
      evolution. Whereas a nonphylogenetic regression was relatively inaccurate and
      biased, independent contrasts accurately estimated the correlation between
      characters with little bias.

PMID- 10937217
TI  - Disease, frequency-dependent selection, and genetic polymorphisms: experiments
      with stripe rust and wheat.
AB  - Pathogens have the potential to maintain genetic polymorphisms by creating
      frequency-dependent selection on their host. This can occur when a rare host
      genotype is less likely to be attacked by a pathogen (frequency-dependent disease
      attack) and has higher fitness at low frequency (negative frequency-dependent
      selection). In this study, we used wheat genotypes that were susceptible to
      different races of the pathogen Puccinia striiformis to test whether disease
      created frequency-selection on its host and whether such selection could maintain
      polymorphisms for resistance genes in the wheat populations. Four different two
      way mixtures of wheat genotypes were planted at different frequencies in both the
      presence and absence of disease. Disease created frequency-dependent selection on
      its host in some populations. Unknown factors other than disease also created
      frequency-dependent selection in this system because, in some instances, rare
      genotype advantage was observed in the absence of disease. Although the pathogen
      created frequency-dependent selection on its host, this selection was not
      sufficient to maintain genetic polymorphism in the host populations. In all cases
      where frequency-dependent selection occurred only in the diseased plots, one of
      the two genotypes was predicted to dominate in the population and the same
      genotype was predicted to dominate in both the presence and absence of disease.
      Only in cases where frequency-dependent selection was not caused by disease was
      there evidence that genetic polymorphisms would be maintained in the population.
      The frequency-dependent selection described in this study is a consequence of
      epidemiological effects of disease and differs from the time-lagged frequency
      dependent selection resulting from coevolution between hosts and parasites. The
      impact of this direct frequency-dependent selection on the maintenance of genetic
      polymorphisms in the host population is discussed.

PMID- 10937218
TI  - The ecology and genetics of fitness in Chlamydomonas. IX. The rate of
      accumulation of variation of fitness under selection.
AB  - Populations of Chlamydomonas founded by single cells were cultured in chemostats
      for 50 days, representing about 125 generations. The mean and variance of
      division rate was measured daily by withdrawing cells from the effluent and
      culturing them for 24 h on filtered effluent medium solidified with agar. Mean
      fitness did not change during the period of culture, and the behavior of neutral
      markers indicated that no substitutions of novel beneficial mutations occurred.
      However, the variance of fitness increased markedly at about the same rate in two
      replicate populations. The standardized rate, or mutational heritability, was
      Vm/VE = 4-5 x 10(-3) per generation. This is substantially greater than most
      other estimates for characters closely correlated with fitness. Moreover, it
      seems difficult to reconcile with the absence of any change in mean fitness. We
      investigated the possibility that frequency-dependent selection was created by
      spatial heterogeneity within the culture vessel by testing cell populations with
      different phenotypes from the top, bottom, and surface of the chemostats.
      However, the differentiation of these populations seemed to be attributable to
      phenotypic plasticity, with no evidence that their characteristics were
      heritable. Finally, we report an experiment in which lines were selected for
      about 100 generations on solid or liquid medium. These lines became specifically
      adapted to the medium on which they were cultured, showing that liquid and solid
      media, even when chemically identical, provide different conditions of growth for
      Chlamydomonas. The genetic variance appearing in the cultures was therefore
      attributed to conditionally neutral mutations that were not expressed in the
      chemostat. This implies that rates of accumulation of mutational variance
      measured in the culture environment itself (where this can be done) may greatly
      underestimate the variation available for a response through selection to
      environmental change. Moreover, it suggests that chemostat populations may be
      more dynamic and more diverse than is usually thought.

PMID- 10937219
TI  - The ecology and genetics of fitness in Chlamydomonas. X. The relationship between
      genetic correlation and genetic distance.
AB  - A necessary condition for the maintenance of genetic variation in heterogeneous
      environments is that the relative fitnesses of a collection of genotypes vary as
      conditions of growth change. This can be detected by estimating the amount of
      gene-by-environment interaction (G x E) when a range of types are tested across a
      range of conditions. However it is the sign and magnitude of the genetic
      correlation, which is a component of G x E, that governs the ultimate fate of
      variation. Whether genetic variation will be preserved, then, depends on how the
      genetic correlation changes as a function of the ecological differences among
      environments and the genetic differences among genotypes. To evaluate this, we
      assayed the performance of 15 chlorophyte species of known genetic relation in 20
      environments. We found that the quantity of G x E increased as both the
      environmental variance across environments and the genetic distance increased.
      Moreover the genetic correlation declined as the environmental variance between
      pairs of environments and the genetic distance between pairs of genotypes
      increased. These results suggest that divergent selection will be more likely to
      maintain genetic variation when environments are strongly contrasted and
      genotypes widely divergent.

PMID- 10937220
TI  - Local adaptation, resistance, and virulence in a hemiparasitic plant-host plant
      interaction.
AB  - Coevolution may lead to local adaptation of parasites to their sympatric hosts.
      Locally adapted parasites are, on average, more infectious to sympatric hosts
      than to allopatric hosts of the same species or their fitness on the sympatric
      hosts is superior to that on allopatric hosts. We tested local adaptation of a
      hemiparasitic plant, Rhinanthus serotinus (Scrophulariaceae), to its host plant,
      the grass Agrostis capillaris. Using a reciprocal cross-infection experiment, we
      exposed host plants from four sites to hemiparasites originating from the same
      four sites in a common environment. The parasites were equally able to establish
      haustorial connections to sympatric and allopatric hosts, and their performance
      was similar on both host types. Therefore, these results do not indicate local
      adaptation of the parasites to their sympatric hosts. However, the parasite
      populations differed in average biomass and number of flowers per plant and in
      their effect on host biomass. These results indicate that the virulence of the
      parasite varied among populations, suggesting genetic variation. Theoretical
      models suggest that local adaptation is likely to be detected if the host and the
      parasite have different evolutionary potentials, different migration rates, and
      the parasite is highly virulent. In the interaction between R. serotinus and A.
      capillaris all the theoretical prerequisites for local adaptation may not be
      fulfilled.

PMID- 10937221
TI  - Plasticity versus canalization: population differences in the timing of shade
      avoidance responses.
AB  - The reliability of environmental cues and costs of a fixed phenotype are two
      factors determining whether selection favors phenotypic plasticity or
      environmental specialization. This study examines the relationship between these
      two factors and the evolution of plant competitive strategies (plastic vs. fixed
      morphologies). In natural plant populations, shifts in light quality associated
      with foliar shade reliably indicate the presence of neighbors. These cues mediate
      plastic stem-elongation responses that often increase competitive ability and
      access to light. Using experimental light treatments (full sun, neutral shade,
      and foliar shade), genetic differences among populations of Abutilon theophrasti
      (velvetleaf) in average elongation and plasticity to foliar-shade cues were
      examined. Six populations, two from each of three site types (fields in
      continuous corn cultivation, fields undergoing corn-soy rotation, and weedy
      sites), were exposed to the light treatments at two stages in their life history.
      At the seedling stage, populations derived from cornfield sites exhibited higher,
      average elongation than populations from either rotating corn-soy fields or weedy
      areas. Because seedling elongation may delay shading of velvetleaf by corn,
      population differences may reflect adaptive responses to directional selection
      imposed by competitive conditions. However, the effects of simulated foliar shade
      on elongation were three times as great as the average population differences,
      and these comparatively higher levels of elongation were associated with an
      allocation cost. These results are consistent with the hypothesis that phenotypic
      plasticity may limit the evolution of specialists; reliable environmental cues
      enable individuals to facultatively adopt highly elongated, costly phenotypes in
      crowded patches while avoiding the costs of that phenotype in less crowded
      microsites. At later life-history stages, populations experiencing competition
      with corn exhibited lower plasticity to light quality than populations derived
      from weedy areas. Elongation at later nodes is maladaptive in cornfields because
      velvetleaf is ultimately incapable of overtopping corn; individuals that elongate
      therefore experience the cost of allocating to stems but fail to improve leaf
      exposure. The decreased responsiveness of cornfield populations to light quality
      is consistent with theoretical predictions in which reduced plasticity is favored
      when environmental cues fail to mediate an adaptive response.

PMID- 10937222
TI  - Quantitative genetics and the persistence of environmental effects in clonally
      propagated organisms.
AB  - Phenotype is often viewed as a product of genes and the environment in which
      these genes are expressed. However, numerous studies have shown that environment
      can cause lasting changes in phenotype that can be passed from one generation to
      the next, much as genes are transmitted. In clonally propagated organisms,
      persistence of environmental effects has been observed in a range of plant and
      animal species, but has rarely been the object of study. We measured the
      persistence and magnitude of environmental effects on phenotype over three clonal
      generations in the arctic sedge Eriophorum vaginatum. We found that the
      environment in which tillers developed had large effects on their later
      performance (parental effects) and that these effects were in part independent of
      the size of tillers. The magnitude and persistence of environmental effects did
      not differ between environmental treatments or among genotypes. However, after 52
      weeks of growth and two rounds of clonal propagation, grandparental treatment
      effects were not significant. We describe methods that can be used in
      quantitative genetics studies of clonal organisms to reduce bias in estimates of
      genotypic and environmental variance and argue that the persistence of
      environmental effects in clonal plant material has ecological and evolutionary
      consequences similar to those described for maternal environmental effects in
      sexual organisms.

PMID- 10937223
TI  - Evolutionary changes over the fifty-year history of a hybrid population of
      sunflowers (Helianthus).
AB  - Although there are many studies of the evolution and ecology of hybrid zones, few
      extend over long enough time periods to track evolutionary changes in the zones
      or assess the ultimate outcome of hybridization. Here we describe the current
      genetic and morphological composition of a hybrid sunflower population relative
      to its initial makeup 50 years ago. It appears that few genetically pure parental
      plants remain in the hybrid population and the average phenotype has shifted from
      an initial bias toward Helianthus bolanderi to a predominance of H. annuus-like
      plants. The similarity to H. annuus is more pronounced for morphology than for
      neutral genetic markers. In contrast to the shift in morphology that occurred
      primarily in the past 40 years, overall pollen viability increased to its current
      level during the first 10 to 15 years of hybridization, indicating the presence
      of strong fertility selection. Dramatic differences are seen in morphology,
      genetics, and pollen viability between the eastern and western halves of the
      population, thus confirming observations by previous authors and suggesting that
      selection pressures in the two halves differ. The trends seen in this hybrid
      population over the past 50 years suggest that H. bolanderi is undergoing genetic
      assimilation, and this trend may be representative of its fate throughout its
      range.

PMID- 10937224
TI  - Estimating phylogenetic inertia in Tithonia (Asteraceae): a comparative approach.
AB  - Phylogenetic inertia is a difficult issue in evolutionary biology because we have
      yet to reach a consensus about how to measure it. In this study a comparative
      approach is used to evaluate phylogenetic inertia in 14 demographic and
      morphological characters in 10 species and one subspecies of the genus Tithonia
      (Asteraceae). Three different methods, autocorrelational analysis, phylogenetic
      correlograms, and ancestor-state reconstruction, were used to evaluate
      phylogenetic inertia in these traits. Results were highly dependent on the method
      applied. Autoregression and phylogenetic eigenvector regression (PVR) methods
      found more inertia in morphological traits. In contrast, phylogenetic
      correlograms and ancestor-state reconstruction suggest that morphological
      characters exhibit less phylogenetic inertia than demographic ones. The
      differences between results are discussed and methods are compared in an effort
      to understand phylogenetic inertia more thoroughly.

PMID- 10937225
TI  - Outbreeding depression varies among cohorts of Ipomopsis aggregata planted in
      nature.
AB  - Outbreeding depression in progeny fitness may arise from disruption of local
      adaptation, disruption of allelic coadaptation, or a combination of these
      "environmental" and "physiological" mechanisms. Thus the minimum spatial scale
      over which outbreeding depression arises should depend on the spatial scale of
      gene dispersal and (with an environmental mechanism) of change in selection
      regimes. We previously reported substantial outbreeding depression in lifetime
      fitness of progeny resulting from crosses among parents separated by 100 m in
      natural populations of the herbaceous plant Ipomopsis aggregata. In this paper we
      explore the effect of crossing distance on fitness in two additional experiments
      begun in 1987 and 1990. We planted seed progeny derived from partial diallel
      crossing designs in randomized blocks in maternal environments and scored
      emergence of seedlings, survival, and eventual flowering of individuals over the
      subsequent six to eight years. Nested within each diallel design were crossing
      distances of 1 m, 10 m, and 100 m. Compared to 1-m and 10-m progeny, 100-m
      progeny of the 1987 diallel suffered a significant reduction in seedling
      emergence, and both 1-m and 100-m progeny that survived to flower achieved lower
      lambda-values on average than 10-m progeny. Total outbreeding depression suffered
      by 100-m relative to 10-m progeny was approximately 10%, compared to
      approximately 30% in our earlier study of I. aggregata. Progeny of 10-m crosses
      also outperformed 1-m and 100-m progeny of the 1990 diallel by approximately 5%,
      but no difference among crossing distance treatments was significant. Thus, the
      magnitude of outbreeding depression in 100-m crosses varied among experiments.
      This is not surprising given likely spatial and temporal variation in gene flow
      and selection regimes, different population histories, and different parental and
      progeny environments. Characterizing outbreeding depression on the shortest
      spatial scales over which it is expressed, as well as its variation and causes,
      is worthwhile because it promises to shed light on the earliest stages of
      angiosperm speciation.

PMID- 10937226
TI  - Variation of shell shape in the clonal snail Melanoides tuberculata and its
      consequences for the interpretation of fossil series.
AB  - Interpreting paleontological data is difficult because the genetic nature of
      observed morphological variation is generally unknown. Indeed, it is hardly
      possible to distinguish among several sources of morphological variation
      including phenotypic plasticity, sexual dimorphism, within-species genetic
      variation or differences among species. This can be addressed using fossil
      organisms with recent representatives. The freshwater snail Melanoides
      tuberculata ranks in this category. A fossil series of this and other species
      have been studied in the Turkana Basin (Kenya) and is presented as one of the
      best examples illustrating the punctuated pattern of evolution by the tenants of
      this theory. Melanoides tuberculata today occupies most of the tropics. We
      studied variation of shell shape in natural populations of this parthenogenetic
      snail using Raup's model of shell coiling. We considered different sources of
      variation on estimates of three relevant parameters of Raup's model: (1)
      variation in shell shape was detected among clones, and had both genetic and
      environmental bases; (2) sexual dimorphism, in those clones in which males occur,
      appeared as an additional source of shell variation; and (3) ecophenotypic
      variation was detected by comparing samples from different sites and years within
      two clones. We then tested the performance of discriminant function analyses, a
      classical tool in paleontological studies, using several datasets. Although the
      three sources of variation cited above contributed significantly to the observed
      morphological variance, they could not be detected without a priori knowledge of
      the biological entities studied. However, it was possible to distinguish between
      M. tuberculata and a related thiarid species using these analyses. Overall, this
      suggests that the tools classically used in paleontological studies are poorly
      efficient when distinguishing between important sources of within-species
      variation. Our study also gives some empirical bases to the doubts cast on the
      interpretation of the molluscan series of the Turkana Basin.

PMID- 10937227
TI  - Multiple origins of eusociality among sponge-dwelling shrimps (Synalpheus).
AB  - As the most extreme expression of apparent altruism in nature, eusociality has
      long posed a central paradox for behavioral and evolutionary ecology. Because
      eusociality has arisen rarely among animals, understanding the selective
      pressures important in early stages of its evolution remains elusive. Employing a
      historical approach to this problem, we used morphology and DNA sequences to
      reconstruct the phylogeny of 13 species of sponge-dwelling shrimps (Synalpheus)
      with colony organization ranging from asocial pair-bonding through eusociality.
      We then used phylogenetically independent contrasts to test whether sociality was
      associated with evidence of enhanced competitive ability, as suggested by
      hypotheses invoking an advantage of cooperation in crowded habitats. The
      molecular, morphological, and combined data each strongly supported three
      independent origins of monogynous, multigenerational (eusocial) colony
      organization within this genus. Phylogenetically independent contrasts confirmed
      that highly social taxa, with strong reproductive skew, have significantly higher
      relative abundance within the host sponge than do less social taxa, a result that
      was robust to uncertainty in tree topology and varying models of character
      change. A similar tendency for highly social species to share their sponge with
      fewer congener species was suggestive, but not significant. Because unoccupied
      habitat appears to be limiting for many sponge-dwelling shrimp species, these
      data are consistent with hypotheses that cooperative social groups enjoy a
      competitive advantage over less organized groups or individuals, where
      independent establishment is difficult, and that enemy pressure is of central
      importance in the evolution of animal sociality.

PMID- 10937228
TI  - Cospeciation between bacterial endosymbionts (Buchnera) and a recent radiation of
      aphids (Uroleucon) and pitfalls of testing for phylogenetic congruence.
AB  - Previous studies of phylogenetic congruence between aphids and their symbiotic
      bacteria (Buchnera) supported long-term vertical transmission of symbionts.
      However, those studies were based on distantly related aphids and would not have
      revealed horizontal transfer of symbionts among closely related hosts. Aphid
      species of the genus Uroleucon are closely related phylogenetically and overlap
      in geographic ranges, habitats, and parasitoids. To examine support for
      congruence of phylogenies of Buchnera and Uroleucon, sequences from four
      mitochondrial, one nuclear, and one endosymbiont gene (trpB) were obtained.
      Congruence of phylogenies based on pooled aphid genes with phylogenies based on
      trpB was highly significant: Most nodes resolved by trpB corresponded to nodes
      resolved by the pooled aphid genes. Furthermore, no nodes were both inconsistent
      between the trees and strongly supported in both trees. Two kinds of analyses
      testing the null hypothesis of perfect congruence between pairwise combinations
      of datasets and tree topologies were performed: the Kishino-Hasegawa test and the
      likelihood-ratio test. Both tests indicated significant disagreement among most
      pairwise combinations of mitochondrial, nuclear, and symbiont datasets. Because
      rampant recombination among mitochondrial genomes of different aphid species is
      unlikely, inaccurate assumptions in the evolutionary models underlying these
      tests appear to be causing the hypothesis of a shared history to be incorrectly
      rejected. Moreover, trpB was more consistent with the aphid genes as a set than
      any single aphid gene was with the others, suggesting that the symbionts show the
      same phylogeny as the aphids. Overall, analyses support the interpretation that
      symbionts and aphids have undergone strict cospeciation, with no horizontal
      transmission of symbionts even among closely related, ecologically similar aphid
      hosts.

PMID- 10937229
TI  - Evolution of gall morphology and host-plant relationships in willow-feeding
      sawflies (Hymenoptera: Tenthredinidae).
AB  - There are over 200 species of nematine sawflies that induce galls on willows
      (Salix spp.). Most of the species are mono- or oligophagous, and they can be
      separated into seven or eight different groups based on the type of gall that
      they induce. We studied the evolution of different gall types and host plant
      associations by reconstructing the phylogeny of five outgroup and 31 ingroup
      species using DNA sequence data from the mitochondrial cytochrome b gene. Maximum
      parsimony and maximum-likelihood analyses resulted in essentially the same
      phylogeny with high support for important branches. The results show that: (1)
      the galling species probably form a monophyletic group; (2) true closed galls
      evolved only once, via leaf folders; (3) with the possible exception of leaf
      rollers, all gall type groups are mono- or paraphyletic; (4) similar gall types
      are closer on the phylogeny than would be expected by a random process; (5) there
      is an apparent evolutionary trend in galling site from the leaf edge towards the
      more central parts of the host plant; and (6) many willow species have been
      colonized several times, which excludes the possibility of parallel cladogenesis
      between willows and the gallers; however, there are signs of restrictions in the
      evolution of host use. Many of the patterns in the evolutionary history of
      nematine gallers have also been observed in earlier studies on other insect
      gallers, indicating convergent evolution between the independent radiations.

PMID- 10937230
TI  - Why it is difficult to model sperm displacement in Drosophila melanogaster: the
      relation between sperm transfer and copulation duration.
AB  - We have investigated the effects of experimental manipulation of copulation
      duration on sperm displacement in Drosophila melanogaster. Both spermless and
      normal males were used as second (displacing) males in the experiments.
      Displacement induced in the absence of sperm, that is, by males that pass
      accessory gland fluid alone, was a relatively inefficient process and produced
      much lower levels of displacement than normal males. Therefore, the presence of
      second-male sperm is necessary (but unlikely sufficient) for the high levels of
      displacement commonly observed in D. melanogaster. Furthermore, when second
      matings were interrupted at various times after the initiation of copulation, the
      distribution of displacement was strongly bimodal. We conclude that sperm
      transfer is relatively rapid, beginning shortly after the initiation of
      copulation, and is essentially complete before the midpoint of copulation.
      Therefore, sperm transfer bears no simple relation to copulation duration.
      Because it would be difficult to manipulate the numbers of sperm transferred by
      manipulating copulation duration, methods used to study sperm displacement in
      other insect species are unlikely to be appropriate for D. melanogaster. We also
      investigated why males mate for more than twice the duration that appears to be
      necessary to complete sperm transfer. Experimental interruption of first matings
      indicated that the extra copulation time serves to delay female remating, rather
      than to increase that rate at which of offspring are sired before remating.

PMID- 10937231
TI  - Radiation and divergence in the Rhagoletis pomonella species group: inferences
      from allozymes.
AB  - The Rhagoletis pomonella species group has for decades been a focal point for
      debate over the possibility of sympatric speciation via host shift. Here I
      present the first extensive analysis of genetic (allozyme) divergence in the
      pomonella group, including all known taxa/populations except the allopatric
      Mexican population of R. pomonella. The phylogeny is estimated for all four
      described species (pomonella, mendax, zephyria, and cornivora) plus two
      undescribed species (the "flowering dogwood fly" and "sparkleberry fly").
      Allozyme data for two additional populations of uncertain status (the "plum fly"
      and "mayhaw fly") are presented for the first time. Two data sets were analyzed,
      one for 17 loci from 77 populations and one for an additional 12 loci for a
      subset of 12 of these populations, with more than 4000 flies analyzed in total.
      Interspecific Nei unbiased genetic distances were generally small, being as low
      as 0.040. No fixed autapomorphic alleles beyond those already known for R.
      cornivora and R. zephyria were revealed in the new data, but several loci
      displaying frequency patterns useful in discriminating the species were
      discovered. The phylogenetic placement of the flowering dogwood fly differed
      depending on whether a molecular clock was assumed (UPGMA of Nei distance) or not
      assumed (frequency parsimony) for tree building. Other than this, however, trees
      under either assumption were essentially identical. The best tree was used to
      test the prediction of the sympatric speciation hypothesis that sister taxa
      should be broadly sympatric. This prediction was not rejected, but the best tree
      was weakly supported by bootstrap analysis. An unexpected finding was that R.
      pomonella populations representing ends of its strong latitudinal clines did not
      cluster together. One possible explanation is that the current R. pomonella is
      the result of a genetic fusion of two previously isolated, genetically
      differentiated populations. Such a fusion prior to the origin of the other
      species in the group could contribute to the poor resolution of the phylogeny.

PMID- 10937232
TI  - Lifetime selection on adult body size and components of body size in a
      waterstrider: opposing selection and maintenance of sexual size dimorphism.
AB  - Sexual size dimorphism (SSD), the difference in body size between males and
      females, is common in almost all taxa of animals and is generally assumed to be
      adaptive. Although sexual selection and fecundity selection alone have often been
      invoked to explain the evolution of SSD, more recent views indicate that the
      sexes must experience different lifetime selection pressures for SSD to evolve
      and be maintained. We estimated selection acting on male and female adult body
      size (total length) and components of body size in the waterstrider Aquarius
      remigis during three phases of life history. Opposing selection pressures for
      overall body size occurred in separate episodes of fitness for females in both
      years and for males in one year. Specific components of body size were often the
      targets of the selection on overall body size. When net adult fitness was
      estimated by combining each individual's fitnesses from all episodes, we found
      stabilizing selection in both sexes. In addition, the net optimum overall body
      size of males was smaller than that of females. However, even when components of
      body size had experienced opposing selection pressures in individual episodes, no
      components appeared to be under lifetime stabilizing selection. This is the first
      evidence that contemporary selection in a natural population acts to maintain
      female size larger than male size, the most common pattern of SSD in nature.

PMID- 10937233
TI  - Intraspecific variation in sexual isolation in the jewel wasp Nasonia.
AB  - Divergence in mate recognition systems can lead to reproductive isolation. In
      this study, we investigate patterns of intraspecific variation that contribute to
      premating isolation within and between two haplodiploid species, Nasonia
      vitripennis and N. longicornis. In a broad-scale survey of 17 North American
      isofemale lines encompassing the two species, we report strong asymmetric sexual
      isolation between species and a dramatic level of intraspecific variation for
      mate discrimination between species. A general lack of incipient speciation was
      found, with the exception of low levels of interpopulational sexual isolation
      within N. vitripennis. Regression analysis shows that the degree of intraspecific
      variation for within-species mating frequency is not associated with the degree
      for between-species mating frequency. Reinforcement or reproductive character
      displacement may be involved in some of the variation in interspecies premating
      isolation.

PMID- 10937234
TI  - Patterns of trait divergence between populations of the meadow grasshopper,
      Chorthippus parallelus.
AB  - To understand the process of speciation, we need to identify the evolutionary
      phenomena associated with divergence between populations of the same species. A
      powerful approach is to compare patterns of trait differences between populations
      differing in their evolutionary histories. A recent study of genetic divergence
      between populations of the meadow grasshopper Chorthippus parallelus, from
      different locations around Europe has allowed us to use this species to
      investigate which aspects of evolutionary history are associated with divergence
      in morphology and mating signals. During the last glaciation C. parallelus was
      confined to a number of refugia in southern Europe and has subsequently
      recolonized the northern part of the continent. This process of isolation
      followed by range expansion has created populations differing markedly in their
      evolutionary pasts--some have been isolated from one another for thousands of
      years, others have undergone repeated founder events, and others now live in
      sympatry with a closely related species. Using laboratory-reared grasshoppers
      from 12 different populations with a range of evolutionary histories, we quantify
      differences in morphology, chemical signals, and male calling-song. The observed
      pattern of divergence between these populations is then compared with the pattern
      predicted by hypotheses about what drives divergence. This comparison reveals
      that long periods in allopatry and processes associated with repeated founder
      events are both strongly associated with divergence.

PMID- 10937235
TI  - Extraordinary multilocus genetic organization in mole crickets, Gryllotalpidae.
AB  - Allozymic diversity at 21 loci was analyzed in 470 individuals of three species
      of mole cricket superspecies, Gryllotalpa gryllotalpa (two new chromosomal
      species, G. tali and G. marismortui) and G. africana in Israel, which are
      distributed along a southward transect of increasing aridity. Two outstanding
      findings emerged in G. tali and G. marismortui: (1) genetic polymorphism was high
      but heterozygosity very low, indicating significant deviations from Hardy
      Weinberg expectations; and (2) significant linkage disequilibria at an
      unprecedented level for outbreeders and remarkable intersite differences. The
      results may characterize subterranean gryllotalpids worldwide because a single
      sample of Neocurtilla hexadactyla from Tefe, Amazonia, shows the same features.
      Significant variation of heterozygote paucity among loci, combined with the
      biology of the species, rejects the simple explanation of inbreeding or any other
      single explanatory model. Likewise, direct selection against heterozygotes or
      specific multilocus associations can explain, but is not necessary nor likely to
      explain, the observed results in mole crickets. To explain these results, we
      developed a multiple-factor mathematical model combining niche viability
      selection, niche choice, and positive assortative mating. This model involves a
      special case of Wahlund effect and inbreeding. Simulations based on this model
      showed that a combination of these three mechanisms may produce the observed
      distribution of alleles, via selection on a few loci, to affect the entire genome
      organization.

PMID- 10937236
TI  - A formal assessment of gene flow and selection in the fire ant Solenopsis
      invicta.
AB  - Recent studies of the introduced fire ant Solenopsis invicta suggest that
      introduced polygyne (with multiple queens per nest) populations are strongly
      influenced by male-mediated gene flow from neighboring monogyne (single queen per
      nest) populations and selection acting on a single locus, general protein-9 (Gp
      9). This investigation formally tests this hypothesis and determines if these
      processes can account for the genotypic structure of polygyne S. invicta. To
      increase the statistical power of this test, we considered the genotypes of
      polygyne queens and workers at both Gp-9 and the closely linked, selectively
      neutral locus Pgm-3. We then constructed and analyzed a novel mathematical model
      to delimit the effects of monogyne male gene flow and selection on the joint
      genotypes at the Pgm-3/Gp-9 superlocus. Using this framework, a hierarchical
      maximum-likelihood method was developed to estimate the best-fitting gene flow
      and selection parameters based on the fit of our model to data from both the
      current study and an earlier one of the same population. In each case, selection
      on polygyne queens and workers alone, with no monogyne male gene flow, provides
      the most parsimonious explanation for the observed genotype frequencies. The
      apparent discrepancy between this result and the empirical evidence for monogype
      male gene flow indicates that undocumented factors, such as other forms of
      selection in polygyne males or workers, are operating in introduced polygyne S.
      invicta.

PMID- 10937237
TI  - The evolution of filial cannibalism and female mate choice strategies as
      resolutions to sexual conflict in fishes.
AB  - Filial cannibalism (the consumption of one's own viable offspring) is common
      among fish with paternal care. In this study, I use a computer simulation to
      study simultaneous evolution of male filial cannibalism and female mate choice.
      Under certain conditions, selection on parental males favors filial cannibalism.
      When filial cannibalism increases a male's probability to raise the current brood
      successfully, filial cannibalism also benefits the female. However, when egg
      eating is a male investment into future reproduction, a conflict between female
      and male interests emerges. Here I investigate how female discrimination against
      filial cannibals affects evolution of filial cannibalism and how different female
      choice criteria perform against filial cannibalism. The introduction of
      discriminating females makes the fixation of filial cannibalism less likely. I
      introduced three different female choice criteria: (1) females who could discern
      a male's genotype, that is, whether the male was going to eat eggs as an
      investment in future reproductive events; (2) energy-choosing females that
      preferred to mate with males who had enough energy reserves to live through the
      current brood cycle without consuming eggs; and (3) females that preferred to
      mate with already mated males, that is, males with eggs in their nest. Genotype
      choice never coexisted with filial cannibals at fixation and filial cannibals
      were unable to invade a population with genotype-choosing females. Energy choice
      was successful only when males had high energy reserves and were less dependent
      on filial cannibalism as an alternative energy source. The egg choosers
      frequently coexisted with the cannibals at fixation. When the female strategies
      were entered simultaneously, the most frequent outcome for low mate sampling
      costs was that both the cannibals and the egg choice was fixed and all other
      strategies went extinct. These results suggest that sexual conflicts may not
      always evolve toward a resolution of the conflict, but sometimes the stable state
      retains the conflict. In the present case, this was because the egg-preference
      strategy had a higher fitness than the other female strategies. The outcome of
      this simulation is similar to empirical findings. In fish with paternal care,
      male filial cannibalism and female preference for mates with eggs commonly co
      occur.

PMID- 10937238
TI  - Selection against late emergence and small offspring in Atlantic salmon (Salmo
      salar).
AB  - Timing of breeding and offspring size are maternal traits that may influence
      offspring competitive ability, dispersal, foraging, and vulnerability to
      predation and climatic conditions. To quantify the extent to which these maternal
      traits may ultimately affect an organism's fitness, we undertook laboratory and
      field experiments with Atlantic salmon (Salmo salar). To control for confounding
      effects caused by correlated traits, manipulations of the timing of fertilization
      combined with intraclutch comparisons were used. In the wild, a total of 1462
      juveniles were marked at emergence from gravel nests. Recapture rates suggest
      that up to 83.5% mortality occurred during the first four months after emergence
      from the gravel nests, with the majority (67.5%) occurring during the initial
      period ending 17 days after median emergence. Moreover, the mortality was
      selective during this initial period, resulting in a significant phenotypic shift
      toward an earlier date of and an increased length at emergence. However, no
      significant selection differentials were detected thereafter, indicating that the
      critical episode of selection had occurred at emergence. Furthermore,
      standardized selection gradients indicated that selection was more intense on
      date of than on body size at emergence. Timing of emergence had additional
      consequences in terms of juvenile body size. Late-emerging juveniles were smaller
      than early-emerging ones at subsequent samplings, both in the wild and in
      parallel experiments conducted in seminatural stream channels, and this may
      affect success at subsequent size-selective episodes, such as winter mortality
      and reproduction. Finally, our findings also suggest that egg size had fitness
      consequences independent of the effects of emergence time that directly affected
      body size at emergence and, in turn, survival and size at later life stages. The
      causality of the maternal effects observed in the present study supports the
      hypothesis that selection on juvenile traits may play an important role in the
      evolution of maternal traits in natural populations.

PMID- 10937239
TI  - Concordance of genetic divergence among sockeye salmon populations at allozyme,
      nuclear DNA, and mitochondrial DNA markers.
AB  - We examined genetic variation at 21 polymorphic allozyme loci, 15 nuclear DNA
      loci, and mitochondrial DNA in four spawning populations of sockeye salmon
      (Oncorhynchus nerka) from Cook Inlet, Alaska, to test for differences in the
      patterns of divergence among different types of markers. We were specifically
      interested in testing the suggestion that natural selection at allozyme loci
      compromises the effectiveness of these markers for describing the amount and
      patterns of gene flow among populations. We found concordance among markers in
      the amount of genetic variation within and among populations, with the striking
      exception of one allozyme locus (sAH), which exhibited more than three times the
      amount of among-population differentiation as other loci. A consideration of
      reports of discordance between allozymes and other loci indicates that these
      differences usually result from one or two exceptional loci. We conclude that it
      is important to examine many loci when estimating genetic differentiation to
      infer historical amounts of gene flow and patterns of genetic exchange among
      populations. It is less important whether those loci are allozymes or nuclear DNA
      markers.

PMID- 10937240
TI  - Restricted gene flow and incipient speciation in disjunct Pacific Ocean and Sea
      of Cortez populations of a reef fish species, Girella nigricans.
AB  - Population disjunctions have been proposed to play an important role in
      speciation processes. In this study, we have examined the possible role of the
      Pacific Ocean-Sea of Cortez disjunction as a contributing factor to cryptic
      speciation in a reef fish, the opaleye, Girella nigricans. Mitochondrial control
      region (D-loop) sequences (380 bp) of 117 individuals completely separated
      opaleye populations from the Pacific Ocean and the Sea of Cortez. Although
      opaleye exhibit pelagic larval stages that remain in the water column for several
      months, gene flow between the Pacific Ocean and the Sea of Cortez was found to be
      extremely limited (FST = 0.84, Nm = 0.10). Whereas limited gene flow and
      reciprocal monophyly suggest that the observed physical and genetic disjunction
      are potentially contributing to the incipient speciation of Pacific and Sea of
      Cortez opaleye, moderate levels of D-loop sequence divergence (3.3%) and the
      absence of fixed allozyme markers challenge this idea. Pacific Coast populations
      also exhibited restricted gene flow levels (FST = 0.25, Nm = 1.49) across Punta
      Eugenia, a recognized oceanographic boundary along the Baja California coast.
      Thus, opaleye individuals grouped into three clades: one clade in the Sea of
      Cortez, one Pacific clade south of Punta Eugenia, and one Pacific clade north of
      Punta Eugenia. Future work in this region will determine if our results can be
      generalized to other disjunct populations.

PMID- 10937241
TI  - Mating preference functions of individual female barking treefrogs, Hyla
      gratiosa, for two properties of male advertisement calls.
AB  - A mating preference function describes the relationship between variation in a
      trait in potential mates and the strength of the preference for that trait. Few
      studies have measured mating preference functions either at a population level or
      for individuals. We used two-choice playback experiments to determine the mating
      preference functions of individual female barking treefrogs for two call
      characteristics: call-repetition rate and fundamental frequency. We tested each
      female four times with each pair of stimuli and with three to six pairs of
      stimuli. Individual females exhibited directional preferences for higher call
      rates and stabilizing preferences for intermediate fundamental frequency. These
      individual preference functions were similar to population-level preferences
      documented in previous studies. Within a stimulus type (call rate or fundamental
      frequency), nearly all females exhibited the same general preference function.
      However, females varied in the minimum difference between stimuli necessary to
      elicit a unanimous choice for the higher call rate, and they differed in both the
      intermediate fundamental frequency they preferred most and the minimum difference
      in fundamental frequency that elicited a unanimous choice for one of the two
      alternatives. The variation we observed among females was not repeatable;
      repeatabilities were in general low and statistically nonsignificant. The
      observed variation in the preferences of females, even if unrepeatable, should
      weaken selection on male traits relative to selection in the absence of such
      variation.

PMID- 10937242
TI  - Evolution of passerine incubation behavior: influence of food, temperature, and
      nest predation.
AB  - Incubation behavior is one component of reproductive effort and thus influences
      the evolution of life-history strategies. We examined the relative importance of
      body mass, frequency of mate feeding, food, nest predation, and ambient
      temperature to explain interspecific variation in incubation behavior (nest
      attentiveness, on- and off-bout durations, and nest trips per hour) using
      comparative analyses for North American passerines in which only females
      incubate. Body mass and frequency of mate feeding explained little variation in
      incubation behavior. We were also unable to detect any influence of foot; diet
      and foraging strategy explained little interspecific variation in incubation
      behavior. However, the typical temperature encountered during reproduction
      explained significant variation in incubation behavior: Species breeding in
      colder environments take shorter bouts off the nest, which prevents eggs from
      cooling to temperatures below the physiological zero temperature. These species
      must compensate for shorter off-bouts by taking more of them (thus shorter on
      bouts) to obtain needed energy for incubation. Nest predation also explains
      significant variation in incubation behavior among passerines: Species that
      endure high nest predation have evolved an incubation strategy (long on- and off
      bouts) that minimizes activity that could attract predators. Nest substrate
      explained additional variation in incubation behavior (cavity-nesting birds have
      shorter on-bouts and make more frequent nest trips), presumably because nest
      predation and/or temperature varies among nest substrates. Thus, nest predation
      can influence reproductive effort in a way previously not demonstrated--by
      placing a constraint on parental activity at the nest. Incubating birds face an
      ecological cost associated with reproductive effort (predation of entire brood)
      that should be considered in future attempts to explain avian life-history
      evolution.

PMID- 10937243
TI  - Effect of deleterious mutation-accumulation on the fitness of RNA bacteriophage
      MS2.
AB  - RNA viruses show the highest mutation rate in nature. It has been extensively
      demonstrated that, in the absence of purifying selection, RNA viruses accumulate
      deleterious mutations at a high rate. However, the parameters describing this
      accumulation are, in general, poorly understood. The present study reports
      evidences for fitness declines by the accumulation of deleterious mutations in
      the bacteriophage MS2. We estimated the rate of fitness decline to be as high as
      16% per bottleneck transfer. In addition, our results agree with an additive
      model of fitness effects.

PMID- 10937244
TI  - Balancing selection on a floral polymorphism.
AB  - The common morning glory, Ipomoea purpurea, exhibits a flower color polymorphism
      at the W locus throughout the southeastern North America. The W locus controls
      whether flowers will be darkly pigmented (WW), lightly pigmented (Ww), or white
      with pigmented rays (ww). In this report, we describe results of a perturbation,
      or convergence, experiment using five plots designed to determine whether
      balancing selection operates on the W locus. The pattern of gene frequency
      changes obtained are indicative of balancing selection operating at the W locus,
      providing direct evidence that both the alleles are actively maintained by
      selection.

PMID- 10937245
TI  - Genetic variation in the spread of Drosophila subobscura from a nonequilibrium
      population.
AB  - Drosophila subobscura was first identified in North America in the early 1980s,
      and a newer D. subobscura population in Utah appears to have been established
      more than 10 years later. In this study, we use nuclear microsatellite allele
      frequencies, mitochondrial restriction fragment length polymorphism (RFLP) allele
      frequencies, and computer simulations to investigate possible scenarios of how
      this species has spread across North America. Our method develops a 95%
      confidence interval for the maximum and minimum number of founders that could
      have colonized the new population given various scenarios for spread. Unlike many
      other methods, it may be applied to nonequilibrium source populations given
      certain conditions. We find that observed allele frequency differences between
      newer and older D. subobscura populations are consistent with very few
      inseminated females being transported east from the coast in a single step or
      with larger numbers of colonizers invading after several intermediate steps. They
      are not consistent with a large, panmictic population of D. subobscura colonizing
      Utah in a single step.

PMID- 10937246
TI  - Imitating the initial evolutionary stage of a tail ornament.
AB  - Costs of a sexual ornament in its early evolutionary form and the relationship
      between these costs and individual condition may be an important influence in the
      likelihood of possible evolutionary mechanisms involved in the evolution of this
      ornament. We reconstructed the tail shape in hypothetical ancestors of recent
      hirundines (Aves: Hirundinidae), from which the elongation of tail feathers under
      sexual selection might have begun. By elongating the tail in sand martins
      (Riparia riparia, Hirundinidae), we simulated the early evolution of a long
      forked tail--the typical ornament of male hirundines. Birds with initial ornament
      captured smaller insects than controls, which suggests that this ornament imposed
      a cost in terms of impaired foraging. Furthermore, birds with naturally longer
      tails were better able to cope with initial ornament than naturally short-tailed
      birds. If length of tail in sand martins indicates the quality of individuals,
      our results suggest higher costs of this initial ornament for poorer than for
      higher quality individuals. We discuss the potential role of the handicap
      principle and other mechanisms in early evolution of a tail ornament.

PMID- 10937247
TI  - Sexual selection and the evolution of costly female preferences: spatial effects.
AB  - Models of Fisher's runaway process show that if there is a cost to female
      preference, no preference or male trait exaggeration will evolve. Surprisingly,
      this is true no matter how small the cost, which reveals that these models of
      Fisher's process are structurally unstable (Bulmer 1989). Here a model of
      Fisher's runaway process is presented to demonstrate that costly female
      preference evolves very easily when space is explicitly included in the model.
      The only requirement is that the optimal male phenotype changes across the
      species' range. The model shows that the spatial average of the female preference
      and male trait reach an evolutionary equilibrium that is identical to those of
      nonspatial models, but that the preference and male trait can deviate greatly
      from these averages at any point in space. For example, if random mating results
      in the lowest cost to females, then at equilibrium the spatial average preference
      will be zero. Nevertheless, there will be some locations at which females prefer
      males with larger ornaments and others where they prefer males with smaller
      ornaments. Results also show that the structural instability of nonspatial models
      of Fisher's process is less of a problem in spatial models. In particular, many
      of the main qualitative features of cost-free spatial models of Fisher's process
      remain valid even when there are small costs of female preference. Finally, the
      model shows that abrupt changes in the optimal male phenotype across space can
      result in an amplification of this pattern when preference has a small cost, but
      it can also result in a pattern similar to reproductive character displacement.
      Which of these occurs depends on the magnitude of the cost of female preference.
      This suggests that some patterns of reproductive character displacement in nature
      might be explained simply by sexual selection rather than by hybrid dysgenesis
      and reinforcement.

PMID- 10937248
TI  - Stability and evolution of overlapping genes.
AB  - When the same sequence of nucleotides codes for regions of more than one
      functional polypeptide, this sequence contains overlapping genes. Overlap is most
      common in rapidly evolving genomes with high mutation rates such as viruses,
      bacteria, and mitochondria. Overlap is thought to be important as: (1) a means of
      compressing a maximum amount of information into short sequences of structural
      genes; and (2) as a mechanism for regulating gene expression through
      translational coupling of functionally related polypeptides. The stability of
      overlapping codes is examined in relation to the information cost of overlap and
      the mutation rate of the genome. The degree of overlap in a given population will
      tend to become monomorphic. Evolution toward partial overlap of genes is shown to
      depend on a convex cost function of overlap. Overlap does not evolve when
      expression of overlapping genes is mutually exclusive and produced by rare
      mutations to the wild-type genome. Assuming overlap increases coupling between
      functionally related genes, the conditions favoring overlap are explored in
      relation to the kinetics of gene activation and decay. Coupling is most effective
      for genes in which the gene overlapping at its 5' end (leading gene) decays
      rapidly, while the gene overlapping at the 3' end (induced gene) decays slowly.
      If gene expression can feedback on itself (autocatalysis), then high rates of
      activation favor overlap.

PMID- 10937249
TI  - Calorie restriction and aging: a life-history analysis.
AB  - The disposable soma theory suggests that aging occurs because natural selection
      favors a strategy in which fewer resources are invested in somatic maintenance
      than are necessary for indefinite survival. However, laboratory rodents on
      calorie-restricted diets have extended life spans and retarded aging. One
      hypothesis is that this is an adaptive response involving a shift of resources
      during short periods of famine away from reproduction and toward increased
      somatic maintenance. The potential benefit is that the animal gains an increased
      chance of survival with a reduced intrinsic rate of senescence, thereby
      permitting reproductive value to be preserved for when the famine is over. We
      describe a mathematical life-history model of dynamic resource allocation that
      tests this idea. Senescence is modeled as a change in state that depends on the
      resources allocated to maintenance. Individuals are assumed to allocate the
      available resources to maximize the total number of descendants. The model shows
      that the evolutionary hypothesis is plausible and identifies two factors, both
      likely to exist, that favor this conclusion. These factors are that survival of
      juveniles is reduced during periods of famine and that the organism needs to pay
      an energetic "overhead" before any litter of offspring can be produced. If
      neither of these conditions holds, there is no evolutionary advantage to be
      gained from switching extra resources to maintenance. The model provides a basis
      to evaluate whether the life-extending effects of calorie-restriction might apply
      in other species, including humans.

PMID- 10937250
TI  - The effects of predator learning, forgetting, and recognition errors on the
      evolution of warning coloration.
AB  - This paper demonstrates that the specifics of predator avoidance learning,
      information loss, and recognition errors may heavily influence the evolution of
      aposematism. I establish a mathematical model of the change in frequency over
      time of bright individuals of a distasteful prey species. Warning color spreads
      through green beard selection as reformulated by Guilford (1990); bright colored
      forms gain an advantage due to their phenotypic resemblance to other bright
      forms, which have been sampled by the predator. I use a general classical
      conditioning model to examine gradual predator learning and forgetting, and then
      consider the extreme of one-trial learning and no forgetting over time that may
      occur with very toxic prey. The advantage of conspicuous coloration under these
      latter conditions depends upon its role in lowering a constant probability of the
      prey being misidentified and thus mistakenly attacked by a predator, a rarely
      emphasized factor in the evolution of warning coloration. This constant
      probability of mistaken attacks can also be interpreted as a constant probability
      that forgetting has occurred (forgetting does not increase with time) or a
      periodic decision by the predator to resample avoided prey. I show that when
      predators learn and forget gradually, as under the general classical conditioning
      model, it is very difficult for aposematic coloration to become established
      unless bright individuals cross an often high threshold frequency through chance
      factors. In contrast, the conditions expected with highly toxic prey promote the
      evolution of warning coloration more easily, by means from the fixation of very
      bright mutations to the fixation of successive mutations each of which causes a
      small increase in a prey's conspicuousness. The results therefore predict that
      aposematic coloration may have evolved in a different manner in different
      predator and prey systems. They also suggest that it may be extremely difficult
      for warning coloration to evolve in more mildly toxic or distasteful prey outside
      of a mimicry system.

PMID- 10937251
TI  - The evolution of compensation to herbivory in scarlet gilia, Ipomopsis aggregata:
      herbivore-imposed natural selection and the quantitative genetics of tolerance.
AB  - Tolerance is the ability of plants to maintain fitness after experiencing
      herbivore damage. We investigated scarlet gilia tolerance to browsing in the
      framework of phenotypic plasticity using both an operational and candidate trait
      approach. Individuals from full-sib families were split into an artificial
      clipping treatment, a natural-damage treatment, or left as controls. We tested
      for genetic variation in tolerance by evaluating family x herbivory treatment
      interactions on fitness in a mixed model analysis of variance. In addition, we
      used selection analyses to assess the function of flowering phenology and
      compensatory regrowth (via branch production) as candidate tolerance traits. We
      found a strong detrimental fitness effect of browsing and considerable variation
      among sire half-sib families in levels of tolerance (25% to 63% of the fitness of
      controls). There was no evidence of overcompensation at either the population or
      family level and no additive genetic variation in operationally defined
      tolerance. Phenotypic selection analyses provide evidence that early flowering
      and compensatory regrowth function as tolerance characters. We found strong
      linear and correlational selection for early flowering and increased branch
      production for damaged plants and linear selection for apical dominance (reduced
      branchiness) and early flowering in control plants. Moreover, reduced
      phenological delay and increased plasticity in branch production were correlated
      with tolerance. We detected significant additive genetic variation in flowering
      phenology in both treatments and a positive genetic correlation between the
      phenology of control and damaged plants. We found significant additive genetic
      variation in branch production in undamaged and naturally damaged plants, but not
      in clipped plants. Damaged plants exhibited marginally significant additive
      genetic variance in fitness, although its heritability was very low
      (approximately 3.6%). We failed to find additive genetic variation in the fitness
      of control plants. Our results suggest that tolerance traits are under herbivore
      imposed natural selection in this population, but that responses to selection are
      limited by available genetic variation and selective constraints.

PMID- 10937252
TI  - Evolutionary ecology of the tropane alkaloids of Datura stramonium L.
      (Solanaceae).
AB  - Although insect herbivory is frequently assumed to be responsible for the
      maintenance of plant secondary metabolites such as alkaloids, the assumption is
      controversial and experimental evidence for this assumption is sparse. We
      examined natural selection on the two major alkaloids present in the leaves of
      Datura stramonium and found that both alkaloids came under active selection. We
      found negative directional selection for scopolamine (natural selection acting to
      reduce scopolamine levels) and stabilizing selection for hyoscyamine (natural
      selection acting to maintain an intermediate level of hyoscyamine). We also
      present evidence that insect herbivores act as the agents of selection on these
      alkaloids. Finally, we show that there were no trade-offs in resistance to
      different species of insects.

PMID- 10937253
TI  - Evolutionary ecology of Datura stramonium: genetic variation and costs for
      tolerance to defoliation.
AB  - The incorporation of plant tolerance after damage as a new alternative to cope
      with herbivory, as opposed to resistance, opened new avenues for our
      understanding of coevolution between plants and herbivores. Although genetic
      variation on tolerance to defoliation has been detected in some species, few
      studies have been undertaken with nonagricultural species. In this study, we
      explore in the annual weed Datura stramonium the existence of genetic variation
      for tolerance and fitness costs of tolerance. To determine which fitness-related
      trait was responsible for possible differences in tolerance, growth rate, total
      flower and fruit production, and the number of seeds per fruit were recorded.
      Inbred line replicates of D. stramonium from a population of Mexico City were
      exposed to four defoliation levels (0%, 10%, 30%, and 70%). Our results from a
      greenhouse experiment using controlled genetic material (inbred lines) indicated
      that significant genetic variation for tolerance was detected across defoliation
      environments. Defoliation reduced plant fitness from 15% to 25% in the highest
      levels of defoliation. Differences on tolerance among inbred lines were accounted
      by a differential reduction in the proportion of matured fruits across
      defoliation levels (up to 20%). Within defoliation levels, significant genetic
      variation in plant fitness suggests that tolerance could be selected. The
      correlation between fitness values of inbred lines in two environments (with and
      without damage) was positive (rg = 0.77), but not significant, suggesting absence
      of fitness costs for tolerance. The finding of genetic variation on tolerance
      might be either due to differences among inbred lines in their capability to
      overcome foliar damage through compensation or due to costs incurred by inducing
      secondary metabolites. Our results indicate the potential for norms of reaction
      to be selected under a gradient of herbivory pressure and highlights the
      importance of dissecting induced from compensatory responses when searching for
      potential causes of genetic variation on tolerance.

PMID- 10937255
TI  - Patterns of intraspecific diversification in the Piriqueta caroliniana complex in
      southeastern North America and the Bahamas.
AB  - We use chloroplast DNA (cpDNA) variation and nested clade phylogeographic
      analyses to infer the historical processes that have contributed to the high
      level of morphological and ecological diversification present in a group of
      herbaceous perennials (the Piriqueta caroliniana complex) in North America and
      the Bahamas. The presence of morphologically distinct and intercompatible
      varieties (morphotypes) that can be distinguished based on suites of taxonomic
      characters (e.g., leaf shape, pubescence type, stature) and contrasting habitat
      affinities (from marshes to dry pinelands and sand scrub) makes this group
      particularly appropriate for studies of intraspecific diversification. To examine
      the distribution of haplotypes among populations, we sampled 467 individuals from
      55 locations in Florida, Georgia, and the northern Bahamas (Grand Bahama and
      Abaco) and screened each individual for cpDNA variation using restriction
      fragment length polymorphism (RFLP) and heteroduplex analyses. We develop a one
      step haplotype phylogeny for this group and use the geographic distributions of
      haplotypes and clades to test specific phylogeographic hypotheses using the
      methods developed by Templeton and his colleagues (Templeton 1998). In general,
      the distribution of haplotypes was strongly influenced by limited dispersal
      distances, with the more recently derived haplotypes having much lower levels of
      dispersion and lower frequencies in populations than the ancestral haplotypes.
      The patterns of clade and haplotype dispersion and displacement and the
      distribution of morphotypes imply at least three cases of long-distance dispersal
      and one case of historical fragmentation. The historical patterns inferred for
      populations of Piriqueta are consistent with known biogeographical events,
      historical vegetation change, and the concordant patterns of multiple Pleistocene
      refugia that have been observed for a number of other taxa in southeastern North
      America.

PMID- 10937256
TI  - Microevolutionary patterns and processes of the Native Hawaiian colonizing fern
      Odontosoria chinensis (Lindsaeaceae).
AB  - The vascular-plant flora of the Hawaiian Islands is characterized by one of the
      highest rates of species endemism in the world. Among flowering plants,
      approximately 89% of species are endemic, and among pteridophytes, about 76% are
      endemic. At the single-island level, however, rates of species endemism vary
      dramatically between these two groups with 80% of angiosperms and only 6% of
      pteridophytes being single-island endemics. Thus, in many groups of Hawaiian
      angiosperms, it is possible to link studies of phylogeny, evolution, and
      biogeographic history at the interspecific and interisland levels. In contrast,
      the low level of single-island species endemism among Hawaiian pteridophytes
      makes similar interspecific and interisland studies nearly impossible. Higher
      levels of interisland gene flow may account for the different levels of single
      island endemism in Hawaiian pteridophytes relative to angiosperms. The primary
      question we addressed in the present study was: Can we infer microevolutionary
      patterns and processes among populations within widespread species of Hawaiian
      pteridophytes wherein gene flow is probably common? To address this broad
      question, we conducted a population genetic study of the native Hawaiian
      colonizing species Odontosoria chinensis. Data from allozyme analyses allowed us
      to infer: (1) significant genetic differentiation among populations from
      different islands; (2) historical patterns of dispersal between particular pairs
      of islands; (3) archipelago-level patterns of dispersal and colonization; (4)
      founder effects among populations on the youngest island of Hawaii; and, (5) that
      this species primarily reproduces via outcrossing, but may possess a mixed-mating
      system.

PMID- 10937254
TI  - Multilocus interactions restrict gene introgression in interspecific populations
      of polyploid Gossypium (cotton).
AB  - Experimental advanced-generation backcross populations contain individuals with
      genomic compositions similar to those resulting from interspecific hybridization
      in nature. By applying a detailed restriction fragment length polymorphism (RFLP)
      map to 3662 BC3F2 plants derived from 24 different BC1 individuals of a cross
      between Gossypium hirsutum and G. barbadense, large and widespread deficiencies
      of donor (G. barbadense) chromatin were found, and seven independent chromosomal
      regions were entirely absent. This skewed chromatin transmission is best
      accounted for by multilocus epistatic interactions affecting chromatin
      transmission. The observed frequencies of two-locus genotypes were significantly
      different from Mendelian expectations about 26 times more often than could be
      explained by chance (P < or = 0.01). For identical pairs of loci, different two
      locus genotypes occurred in excess in different BC3 families, implying the
      existence of higher-order interlocus interactions beyond the resolution of these
      data. Some G. barbadense markers occurred more frequently than expected by
      chance, indicating that genomic interactions do not always favor host chromatin.
      A preponderance of interspecific allelic interactions involved one locus each in
      the two different subgenomes of (allotetraploid) Gossypium, thus supporting
      several other lines of evidence suggesting that intersubgenomic interactions
      contribute to unique features that distinguish tetraploid cotton from its diploid
      ancestors.

PMID- 10937257
TI  - An association between a floral trait and inbreeding depression.
AB  - Inbreeding depression is a general phenomenon that is well documented in many
      plants and animals. Furthermore, it is generally considered to be the driving
      force behind mating-system evolution. Traditionally, the focus has been on the
      mean level of inbreeding depression in populations. However, more recently, the
      variation in inbreeding depression among individuals within populations has been
      shown to be influential in mating-system evolution. One set of theories predicts
      that genetic associations will develop between a mating-system locus and loci
      causing inbreeding depression, whereas another suggests either that no such
      association will occur or that it will be difficult to detect empirically. Here,
      we focus on variation in inbreeding depression among individuals and present
      empirical evidence of a genetic association between genes causing inbreeding
      depression and a floral trait influencing the mating system (i.e., selfing rate).
      We found a positive association between inbreeding depression and herkogamy (the
      degree to which the stigma and anthers are separated) in an annual plant, Gilia
      achilleifolia. These results are consistent with theory predicting that an
      individual's history of inbreeding will affect its level of inbreeding depression
      and highlight the potential importance of genetic associations between selfing
      modifier traits and viability in mating-system evolution.

PMID- 10937258
TI  - Ontogenetic differences in heterostylous plants and implications for development
      from a herkogamous ancestor.
AB  - Alternative ontogenetic pathways among heterostylous species of Rubiaceae may
      reflect differences in their evolutionary histories. In this study, measurements
      were taken at different developmental stages on a series of long-styled (LS) and
      short-styled (SS) buds of the heterostylous taxa Psychotria chiapensis, P.
      poeppigiana, and Bouvardia ternifolia (all Rubiaceae). Results indicated that
      modifications in growth rates of stamens relative to corollas in all three
      species led to differences in anther heights between LS and SS flowers. Distinct
      style heights for LS and SS flowers of P. chiapensis and P. poeppigiana originate
      in the earlier stages of bud development and are maintained as styles elongate at
      equal rates. This contrasts with B. ternifolia, which has differences in style
      heights resulting from unequal relative growth rates between floral morphs. The
      "approach herkogamous" floral morphology, defined by having stigmas positioned
      above anthers, has been proposed as a potential evolutionary precursor for
      heterostylous taxa. To examine this hypothesis, floral development of two species
      with approach herkogamous morphologies, Psychotria pittieri and P. brachiata, was
      compared to that of the three heterostylous taxa. Differences in the relative
      rates of style elongation for flowers of approach herkogamous versus
      heterostylous species predict additional steps in the original model for the
      evolution of heterostyly from an approach herkogamous ancestor. The diversity of
      heterostylous ontogenies found within Rubiaceae provides insight into potential
      evolutionary pathways for this sexual system in other angiosperm families.

PMID- 10937259
TI  - Crossing relationships among ancient and experimental sunflower hybrid lineages.
AB  - Reproductive barrier formation between newly derived hybrid taxa and their
      parental species represents a major evolutionary hurdle. Here, I examine the
      development of a sterility barrier during hybrid speciation by examining the
      fertility of progeny from all combinations of crosses involving three
      experimentally synthesized sunflower hybrid lineages, their natural hybrid
      counterpart, Helianthus anomalus, and their parents, H. annuus and H. petiolaris.
      Crosses between the parental species and H. anomalus generated almost completely
      sterile offspring (pollen viability < 5%; seed set < 1%). A fairly strong
      sterility barrier also has developed between three hybrid lineages and both
      parental species (pollen viability 11.1-41.6%; seed set 0.84-20.1%). In contrast,
      the three hybrid lineages are almost fully interfertile (pollen viabilities 83.1
      88.6%; seed set 72.1-75.3%), as predicted by molecular mapping studies that
      indicate they have converged on a similar set of gene combinations and
      chromosomal rearrangements. A modest decline in compability is observed in
      crosses between the three hybrid lineages and H. anomalus (pollen viabilities
      64.1-70.7%; seed set 37-43%), a result that agrees well with prior data
      demonstrating significant congruence between the genomes of the natural and
      experimental hybrid lineages. These observations not only indicate that
      reproductive isolation can arise as a by-product of fertility selection in hybrid
      populations, but also testify to the repeatability of this mode of speciation.

PMID- 10937260
TI  - Parental effects and gender specialization in a tropical heterostylous shrub.
AB  - Male sterility in hermaphroditic species may represent the first step in the
      evolution toward dioecy. However, gender specialization will not proceed unless
      the male-sterile individuals compensate for fitness lost through the male
      function with an increase in fitness through the female function. In the
      distylous shrub Erythroxylum havanense, thrum plants are partially male-sterile.
      Using data collected throughout eight years, we investigated whether thrum
      individuals have an increased performance as female parents, thereby compensating
      for their loss of male fitness. We found that thrum plants outperformed pins in
      the probabilities of seed maturation and germination and long-term growth of the
      seedlings. In turn, pollen from pin plants achieved greater pollen tube growth
      rates. Our results suggest that the superior performance of the progeny of thrum
      maternal plants is a consequence of better seed provisioning via effects of the
      maternal environment, cytotype or nuclear genes. Overall, our results suggest
      that E. havanense is evolving toward a dioecious state through a gynodioecious
      intermediate stage. This evolutionary pathway is characterized by an unusual
      pattern of gender dimorphism with thrums becoming females and pins becoming
      males. We propose that this pattern may be better explained by the interaction
      between male-sterility cytoplasmic genes and the heterostyly supergene.

PMID- 10937261
TI  - Maintenance of androdioecy in the freshwater shrimp, Eulimnadia texana: estimates
      of inbreeding depression in two populations.
AB  - Androdioecy is an uncommon form of reproduction in which males coexist with
      hermaphrodites. Androdioecy is thought to be difficult to evolve in species that
      regularly inbreed. The freshwater shrimp Eulimnadia texana has recently been
      described as both androdioecious and highly selfing and is thus anomalous.
      Inbreeding depression is one factor that may maintain males in these populations.
      Here we examine the extent of "late" inbreeding depression (after sexual
      maturity) in these clam shrimp using two tests: (1) comparing the fitness of
      shrimp varying in their levels of individual heterozygosity from two natural
      populations that differ in overall genetic diversity; and (2) specifically
      outcrossing and selfing shrimp from these same populations and comparing fitness
      of the resulting offspring. The effects of inbreeding differed within each
      population. In the more genetically diverse population, fecundity, size, and
      mortality were significantly reduced in inbred shrimp. In the less genetically
      diverse population, none of the fitness measures was significantly lowered in
      selfed shrimp. Combining estimates of early inbreeding depression from a previous
      study with current estimates of late inbreeding depression suggests that
      inbreeding depression is substantial (delta = 0.68) in the more diverse
      population and somewhat lower (delta = 0.50) in the less diverse population.
      However, given that males have higher mortality rates than hermaphrodites,
      neither estimate of inbreeding depression is large enough to account for the
      maintenance of males in either population by inbreeding depression alone. Thus,
      the stability of androdioecy in this system is likely only if hermaphrodites are
      unable to self-fertilize many of their own eggs when not mated to a male or if
      male mating success is generally high (or at least high when males are rare).
      Patterns of fitness responses in the two populations were consistent with the
      hypothesis that inbreeding depression is caused by partially recessive
      deleterious alleles, although a formal test of this hypothesis still needs to be
      conducted.

PMID- 10937262
TI  - Neurobiological constraints and fly systematics: how different types of neural
      characters can contribute to a higher level dipteran phylogeny.
AB  - Much uncertainty still exists regarding higher level phylogenetic relationships
      in the insect order Diptera, and the need for independent analyses is apparent.
      In this paper, I present a parsimony analysis that is based on details of the
      nervous system of flies. Because neural characters have received little attention
      in modern phylogenetic analyses and the stability of neural traits has been
      debated, special emphasis is given to testing the robustness of the analysis
      itself and to evaluating how neurobiological constraints (such as levels of
      neural processing) influence the phylogenetic information content. The
      phylogenetic study is based on 14 species in three nematoceran and nine
      brachyceran families. All characters used in the analysis are based on anatomical
      details of the neural organization of the fly visual system. For the most part
      they relate to uniquely identifiable neurons, which are cells or cell types that
      can be confidently recognized as homologues among different species and thus
      compared. Parsimony analysis results in a phylogenetic hypothesis that favors
      specific previously suggested phylogenetic relationships and suggests
      alternatives regarding other placements. For example, several heterodactylan
      families (Bombyliidae, Asilidae, and Dolichopodidae) are supported in their
      placement as suggested by Sinclair et al. (1993), but Tipulidae and Syrphidae are
      placed differently. Tipulidae are placed at a derived rather than ancestral
      position within the Nematocera, and Syrphidae are placed within the Schizophora.
      The analysis suggests that neural characters generally maintain phylogenetic
      information well. However, by "forcing" neural characters onto conventional
      phylogenetic analyses it becomes apparent that not all neural centers maintain
      such information equally well. For example, neurons of the second-order visual
      neuropil, the medulla, contain stronger phylogenetic "signal" than do characters
      of the deeper visual center, the lobula plate. These differences may relate to
      different functional constraints in the two neuropils.

PMID- 10937263
TI  - Close genetic similarity between two sympatric species of tephritid fruit fly
      reproductively isolated by mating time.
AB  - Two sibling species of tephritid fruit fly, Bactrocera tryoni and B.
      neohumeralis, occur sympatrically throughout the range of B. neohumeralis in
      Australia. Isolation between the two species appears to be maintained by a
      difference in mating time: B. tryoni mates at dusk, whereas B. neohumeralis mates
      during the middle of the day. A morphological difference in humeral callus color
      also distinguishes the two species. Despite clear phenotypic evidence that B.
      tryoni and B. neohumeralis are distinct species, genetic differentiation as
      measured by four markers--nuclear DNA sequences from the white gene and the
      ribosomal internal transcribed spacer (ITS2), and mitochondrial DNA sequences
      from the cytochrome b (cytb) and cytochrome oxidase subunit II (COII) genes--is
      very small. Minor fixed differences occur in the ITS2 sequence, however, in all
      other cases the two species exhibit a high level of shared polymorphic variation.
      The close genetic similarity suggests either that speciation has occurred very
      rapidly and recently in the absence of any mitochondrial DNA sorting or that the
      sharing of polymorphisms is due to hybridization or introgression. A third
      species within the tryoni complex, B. aquilonis, is geographically isolated.
      Bactrocera aquilonis is also genetically very similar, but in this case there is
      clear differentiation for the mitochondrial loci. The three species form a group
      of considerable interest for investigation of speciation mechanisms.

PMID- 10937265
TI  - Optimal copula duration in yellow dung flies: ejaculatory duct dimensions and
      size-dependent sperm displacement.
AB  - We aim to interpret sperm displacement in relation to male size in the yellow
      dung fly, Scatophaga stercoraria, and to compare the general properties of
      indirect and direct size-dependent sperm displacement in insects. We examine the
      hypothesis that male size-dependent sperm displacement in dung flies can be
      explained by size-dependent increases in the ejaculatory apparatus, allowing
      greater sperm flow rates in larger males. We expect sperm flow rates to be
      proportional to the diameter of the aedeagus duct to the power x, where x lies
      between 2 and 3. We test this hypothesis using a simulation model of indirect
      sperm displacement that has been developed to accommodate recent observations on
      sperm transfer, in which sperm flow from the male into the female bursa and are
      then transferred to the spermathecae by movements of the female tract. The
      indirect model approximates to the pattern of size-related sperm displacement,
      with scaling power 3 giving a better fit than power 2. Copula duration shows a
      male size-dependent decrease in this species. We apply the indirect model of
      sperm displacement, in conjunction with parameters obtained from field and
      laboratory data, to predict size-dependent changes in optimal copula duration
      from the male perspective. This model concurs with the observations by predicting
      a size-dependent decline in optimal copula duration, as did an earlier model in
      which displacement was direct (new sperm displace previously stored sperm
      directly from the sperm stores). Our new approach gives a better fit than the
      earlier direct model. Thus, both results (displacement rates and copula duration)
      can be explained by size-dependent changes in the ejaculatory apparatus of the
      male with the female's exchange rate of sperm (from bursa to spermathecae)
      remaining constant with respect to male size, although we discuss the possibility
      that this female process may accelerate with increased male size. In general,
      where the sperm input rate is around the same magnitude as the exchange rate,
      indirect displacement will be dependent on the size of the male, as in dung
      flies, but this dependency is lost if the input rate is very high relative to the
      exchange rate across the entire range of male size. Size-dependent displacement
      should always apply for males with direct displacement.

PMID- 10937264
TI  - Colonization and diversification of the species Brachyderes rugatus (Coleoptera)
      on the Canary Islands: evidence from mitochondrial DNA COII gene sequences.
AB  - The genus Brachyderes Schonherr (Coleoptera: Curculionidae) is represented by the
      species B. rugatus Wollaston on the Canary Islands, with one subspecies on each
      of the islands of Gran Canaria, Tenerife, La Palma, and El Hierro. These four
      subspecies are associated with the endemic pine tree Pinus canariensis, and their
      distributions are broadly coincident. Eighty-eight individual Canarian
      Brachyderes, sampled from across the distributions of each subspecies, have been
      sequenced for 570 bp of the mitochondrial DNA (mtDNA) cytochrome oxidase II gene
      (COII). No mitotypes are shared among islands. Both maximum-likelihood and
      distance-based phylogenetic analyses have shown that: Tenerife is composed of a
      single monophyletic clade of mitotypes, El Hierro is composed of a single
      monophyletic clade occurring within a larger clade comprising all the La Palma
      mitotypes, and the mitotypes of these three islands form a monophyletic group
      distinct from Gran Canaria. New methods for estimating divergence times without
      the assumption of rate constancy have been used to reconstruct the direction and
      approximate timing of colonizations among the islands. Colonization has occurred
      from older to progressionally younger islands, and these colonizations are
      estimated to have occurred less than 2.6 million years ago, although the timing
      of the initial colonization of the archipelago is not discernable. New methods
      for the estimation of diversification rates that use branching times as the
      analyzed variable have been applied to each island fauna. Hypothesized effects of
      different levels of recent volcanism among islands were not apparent. All islands
      exhibit a gradually decreasing rate of genetic diversification that is marked by
      periodic sudden changes in rate.

PMID- 10937266
TI  - Maternal and paternal effects on offspring phenotype in the dung beetle
      Onthophagus taurus.
AB  - Parents often have important influences on the development of traits in their
      offspring. One mechanism by which parents are able to influence offspring
      phenotype is through the level of care they provide. In onthophagine dung
      beetles, parents typically provision their offspring by packing dung fragments
      into a brood mass. Onthophagus taurus males can be separated into two discrete
      morphs: Large, "major" males have head horns, whereas "minor" males are hornless.
      Here we show that a switch in parental provisioning strategies adopted by males
      coincides with the switch in male morphology. Male provisioning results in the
      production of heavier brood masses than females will produce alone. However,
      unlike females in which the level of provisioning increases with body size in a
      continuous manner, the level of provisioning provided by males represents an "all
      or-none" tactic with all major males providing a fixed level of provisioning
      irrespective of their body size. Offspring size is determined largely by the
      quantity of dung provided to the developing larvae so that paternal and maternal
      provisioning affects the body size and horn size of offspring produced. The
      levels of provisioning by individual parents are significantly repeatable,
      suggesting paternal and maternal effects as candidate indirect genetic effects in
      the evolution of horn size in the genus Onthophagus.

PMID- 10937267
TI  - Microsatellite analysis of sperm-use patterns in the bushcricket Requena
      verticalis.
AB  - The proportion of offspring sired by the second male to mate with a doubly mated
      female, P2, is a ubiquitously measured statistic in the study of insect sperm
      competition. Nevertheless, the underlying mechanisms of sperm transfer, storage,
      and use that determine P2 are poorly understood. Typically the second male to
      mate gains moderate to high paternity. More rarely, the first male to mate gains
      the majority of fertilizations. Here we examine the transfer, storage, and use of
      sperm in the bushcricket Requena verticalis, a species with male parental
      investment and almost complete first male paternity. Sperm drain from an
      externally attached spermatophore into the female's reproductive tract, where
      they are transported to the sperm store or spermatheca. We find that only sperm
      from the first male to mate are transported to the spermatheca. We provide some
      data that address a number of different mechanisms that might account for the
      lack of storage of second-male sperm. DNA microsatellite markers are developed to
      assign paternity. By manipulating the numbers of sperm transferred by first and
      second males, we show that the size of the ejaculate transferred by the first
      male has a major impact on paternity; increasing ejaculate size of the first male
      assures his paternity. Paternity assurance in R. verticalis holds significant
      implications for the evolution of paternal investment via the male's nuptial
      gift.

PMID- 10937268
TI  - Genetic variance of sexually selected traits in waxmoths: maintenance by genotype
      x environment interaction.
AB  - When traits experience directional selection, such as that imposed by sexual
      selection, their genetic variance is expected to diminish. Nonetheless, theory
      and findings from sexual selection predict and demonstrate that male traits
      favored by female choice retain substantial amounts of additive genetic variance.
      We explored this dilemma through an ecological genetic approach and focused on
      the potential contributions of genotype x environment interaction (GEI) to
      maintenance of additive genetic variance for male signal characters in the lesser
      waxmoth, Achroia grisella (Lepidoptera: Pyralidae). We artificially selected
      genetic variants for two male signal characters, signal rate (SR) and peak
      amplitude (PA), that influence female attraction and then examined the phenotypic
      plasticity of these variants (high- and low-SR and high- and low-PA lines) under
      a range of environmental conditions expected in natural populations. Our split
      family breeding experiments indicated that two signal characters, SR and PA, and
      several developmental characters in both high- and low-SR and high- and low-PA
      lines displayed considerable phenotypic plasticity among the environments tested.
      Moreover, strong GEIs leading to crossover between high- and low-SR lines were
      found for SR and developmental period. Therefore, neither high- nor low-SR
      genetic variants would achieve maximum attractiveness and fitness in every
      environment, and those variants producing unattractive signals with low SRs under
      normal conditions may remain in populations provided that gene flow across
      environments or generation overlap are sufficiently high. We speculate that the
      phenotypic plasticity for SR and developmental period is adaptive in A. grisella
      populations experiencing a range of temperature and density conditions. Females
      mating with attractive (high-SR) males may be assured of obtaining good genes
      because these males sire offspring that develop more rapidly and a crossover for
      developmental period may parallel that for SR. Such parallel crossovers may be
      expected wherever good-genes sexual selection mechanisms operate.

PMID- 10937269
TI  - Does multiple paternity improve fitness of the frog Crinia georgiana?
AB  - In the Australian myobatrachid frog Crinia georgiana simultaneous polyandry
      occurs in about half of all matings, which leads to multiple paternity, but
      reduced fertilization success and occasional female mortality. Multiple paternity
      may provide benefits to females that compensate for these costs, for example,
      through enhanced genetic diversity of a clutch. In nature, embryos and tadpoles
      of C. georgiana develop in shallow, temporary pools and may be exposed to
      fluctuating water levels and the risk of desiccation between rain events.
      Fertilization by genetically diverse sires may act as a bet hedge against these
      conditions. To evaluate this hypothesis, females were artificially mated with one
      or two males in the field and eggs and larvae reared in the laboratory under
      constant or fluctuating developmental conditions. Experiment 1 exposed embryos
      from single- and multiple-paternity clutches to conditions where eggs were
      completely covered during development or eggs sat in air on a moist substrate.
      Experiment 2 exposed freshly hatched larvae from single- and multiple-paternity
      clutches to constant wet conditions, where larvae were completely covered, or
      fluctuating wet conditions, where larvae ranged from being completely submersed
      to partially exposed over a 13-day cycle. We measured mean performance and best
      performance as alternate measures of genetic benefits. There were no effects of
      paternity on percent survival to hatching, time to hatching, body size at
      hatching, percent survival to metamorphosis, time to metamorphosis, or body size
      at metamorphosis. We also analyzed variance within clutches as a measure of
      genetic diversity. Again there were no predictable effects of multiple paternity.
      Polyandry does not appear to provide any genetic benefits that compensate for the
      high costs of polyandry in this species.

PMID- 10937270
TI  - Mechanisms of population differentiation in marbled murrelets: historical versus
      contemporary processes.
AB  - Mechanisms of population differentiation in highly vagile species such as
      seabirds are poorly understood. Previous studies of marbled murrelets
      (Brachyramphus marmoratus; Charadriiformes: Alcidae) found significant population
      genetic structure, but could not determine whether this structure is due to
      historical vicariance (e.g., due to Pleistocene glaciers), isolation by distance,
      drift or selection in peripheral populations, or nesting habitat selection. To
      discriminate among these possibilities, we analyzed sequence variation in nine
      nuclear introns from 120 marbled murrelets sampled from British Columbia to the
      western Aleutian Islands. Mismatch distributions indicated that murrelets
      underwent at least one population expansion during the Pleistocene and probably
      are not in genetic equilibrium. Maximum-likelihood analysis of allele frequencies
      suggested that murrelets from "mainland" sites (from the Alaskan Peninsula east)
      are genetically different from those in the Aleutians and that these two lineages
      diverged prior to the last glaciation. Analyses of molecular variance, as well as
      estimates of gene flow derived using coalescent theory, indicate that population
      genetic structure is best explained by peripheral isolation of murrelets in the
      Aleutian Islands, rather than by selection associated with different nesting
      habitats. No isolation-by-distance effects could be detected. Our results are
      consistent with a rapid expansion of murrelets from a single refugium during the
      early-mid Pleistocene, subsequent isolation and divergence in two or more refugia
      during the final Pleistocene glacial advance, and secondary contact following
      retreat of the ice sheets. Population genetic structure now appears to be
      maintained by distance effects combined with small populations and a highly
      fragmented habitat in the Aleutian Islands.

PMID- 10937271
TI  - Sexual dimorphism in relation to current selection in the house finch.
AB  - Sexual dimorphism is thought to have evolved in response to selection pressures
      that differ between males and females. Our aim in this study was to determine the
      role of current net selection in shaping and maintaining contemporary sexual
      dimorphism in a recently established population of the house finch (Carpodacus
      mexicanus) in Montana. We found strong differences between sexes in direction of
      selection on sexually dimorphic traits, significant heritabilities of these
      traits, and a close congruence between current selection and observed sexual
      dimorphism in Montana house finches. Strong directional selection on sexually
      dimorphic traits and similar intensities of selection in each sex suggested that
      sexual dimorphism arises from adaptive responses in males and females, with both
      sexes being far from their local fitness optimum. This pattern is expected when a
      recently established population experiences continuous immigration from
      ecologically distinct areas of a species range or as a result of widely
      fluctuating selection pressures, as found in our study. Strong and sexually
      dimorphic selection pressures on heritable morphological traits, in combination
      with low phenotypic and genetic covariation among these traits during growth, may
      have accounted for close congruence between current selection and observed sexual
      dimorphism in the house finch. This conclusion is consistent with the profound
      adaptive population divergence in sexual dimorphism that accompanied very
      successful colonization of most of the North America by the house finch over the
      last 50 years.

PMID- 10937272
TI  - Song variation in an avian ring species.
AB  - Divergence of mating signals can occur rapidly and be of prime importance in
      causing reproductive isolation and speciation. A ring species, in which two
      reproductively isolated taxa are connected by a chain of intergrading
      populations, provides a rare opportunity to use spatial variation to reconstruct
      the history of divergence. I use geographic variation in the song of a likely
      ring species, the greenish warbler (Phylloscopus trochiloides) to reconstruct the
      microevolutionary steps that occurred during divergence of a trait that is often
      important in speciation in birds. Populations of a western Siberian (P. t.
      viridanus) and an eastern Siberian (P. t. plumbeitarsus) form of the greenish
      warbler meet, but do not interbreed in central Siberia; these forms are connected
      by a chain of interbreeding populations extending in a ring to the south around
      the treeless Tibetan Plateau. I show that: (1) song structure differs greatly
      between the two Siberian forms, which share the same habitat; (2) song structure
      changes gradually around the ring; (3) singing behavior is relatively simple in
      the Himalayas, but becomes increasingly complex to the north, both to the west
      and east of the Tibetan Plateau; and (4) song varies along independent axes of
      complexity in the western and eastern south-north clines. By comparing geographic
      variation in singing behavior and ecological variables, I distinguish among
      possible causes of song divergence, including selection based on the acoustic
      environment, stochastic effects of sexual selection, and selection for species
      recognition. I suggest that parallel south-to-north ecological gradients have
      caused a greater intensity of sexual selection on song in northern populations
      and that the stochastic effects of sexual selection have led to divergence in
      song structure.

PMID- 10937273
TI  - Are pinnipeds functionally different from fissiped carnivores? The importance of
      phylogenetic comparative analyses.
AB  - It is widely assumed that adaptations to an aquatic lifestyle are so profound as
      to produce only obvious differences between pinnipeds and the remaining, largely
      terrestrial carnivore species ("fissipeds"). Thus, comparative studies of the
      order Carnivora routinely examine these groups independently. This approach is
      invalid for two reasons. First, fissipeds are a paraphyletic assemblage, which
      raises the general issue of when it is appropriate to ignore monophyly as a
      criterion for inclusion in comparative studies. Second, the claim that most
      functional characters (beyond a few undoubted characteristic features) are
      different in pinnipeds and fissipeds has never been quantitatively examined, nor
      with phylogenetic comparative methods. We test for possible differences between
      these two groups in relation to 20 morphological, life-history, physiological,
      and ecological variables. Comparisons employed the method of independent
      contrasts based on a complete and dated species-level phylogeny of the extant
      Carnivora. Pinnipeds differ from fissipeds only through evolutionary grade shifts
      in a limited number of life-history traits: litter weight (vs. gestation length),
      birth weight, and age of eyes opening (both vs. size). Otherwise, pinnipeds
      display the same rate of evolution as phylogenetically equivalent fissiped taxa
      for all variables. Overall functional differences between pinnipeds and fissipeds
      appear to have been overstated and may be no greater than those among major
      fissiped groups. Recognition of this fact should lead to a more complete
      understanding of carnivore biology as a whole through more unified comparative
      tests. Comparative studies that do not include monophyletic groups for
      phylogenetically based comparative tests should be reconsidered.

PMID- 10937274
TI  - Measuring tolerance to herbivory: accuracy and precision of estimates made using
      natural versus imposed damage.
AB  - Tolerance to herbivory (the ability of a plant to incur herbivore damage without
      a corresponding reduction in fitness) can be measured using either naturally
      occurring or imposed herbivore damage. After briefly reviewing some of the
      advantages and disadvantages of these approaches, we present calculations
      describing the degree to which estimates of tolerance will be biased by
      environmental variables that affect both herbivory and fitness. With naturally
      occurring herbivory the presence of environmental variables that are correlated
      with herbivory and fitness will result in biased estimates of tolerance. In
      contrast, estimates obtained from experiments in which herbivory is artificially
      imposed will be unbiased; however, under a wide range of parameter values these
      estimates will be less precise than estimates obtained from experiments in which
      herbivory is not manipulated.

PMID- 10937275
TI  - Nontransitivity of sperm precedence in Drosophila.
AB  - Sperm competition is an important component of fitness in Drosophila, but we
      still do not have a clear understanding of the unit of selection that is relevant
      to sperm competition. Here we demonstrate that sperm competitive ability is not a
      property of the sperm haplotype, but rather of the diploid male's genotype. Then
      we test whether the relative sperm competitive ability of males can be ranked on
      a linear array or whether competitive ability instead depends on particular
      pairwise contests among males. Sperm precedence of six chromosome-extracted lines
      was tested against three different visible marker lines (cn bw, bwD, and Cy), and
      the rank order of the six lines differed markedly among the mutant lines.
      Population genetic theory has shown that departures from transitivity of sperm
      precedence may be important to the maintenance of polymorphism for genes that
      influence sperm competitive ability. The nontransitivity seen in sperm precedence
      should theoretically increase the opportunity for polymorphism in genes that
      influence this phenotype.

PMID- 10937276
TI  - The genetics of phenotypic plasticity. IX. Genetic architecture, temperature, and
      sex differences in Drosophila melanogaster.
AB  - We examined the genetic architecture of plasticity of thorax and wing length in
      response to temperature in Drosophila melanogaster. Reaction norms as a function
      of growth temperature were analyzed in 20 isofemale lines in a natural population
      collected from Grande Ferrade near Bordeaux (southern France) in two different
      years. We found evidence for a complex genetic architecture underlying the
      reaction norms and differences between males and females. Reaction norms were
      negative quadratics. Genetic correlations were moderately high between traits
      within environments. Among characteristic values, the magnitudes of genetic
      correlations varied among traits and sexes. We hypothesized that genetic
      correlations among environments would decrease as temperatures became more
      different. This expectation was upheld for only one trait, female thorax length.
      For males for both traits, the correlations were large for both very similar and
      very different temperatures. These correlations may constrain the evolution of
      the shape of the reaction norms. Whether the extent of independence implies
      specific regulatory genes or only a specific allelic regulation of trait genes
      can not be decided from our results.

PMID- 10937277
TI  - Parallel evolution of the melanic form of the California legless lizard, Anniella
      pulchra, inferred from mitochondrial DNA sequence variation.
AB  - The phylogenetic relationships among populations of the fossorial California
      legless lizard, Anniella pulchra, were examined by sequencing a 990-bp region of
      the mitochondrial cytochrome b gene. The mitochondrial DNA gene tree was then
      compared with the geographic distributions of two currently recognized
      subspecies: A. p. nigra, a melanic form restricted to two disjunct coastal
      populations, and A. p. pulchra, a more widely distributed, silvery form. We
      tested the null hypothesis that all A. p. nigra form a clade that is monophyletic
      with respect to A. p. pulchra. Our results strongly reject the monophyletic
      origin of the melanic forms and suggest that the two populations of the nominal
      subspecies A. p. nigra may have arisen independently from different ancestral
      populations in a parallel evolutionary response to selection in cool, coastal
      habitats.

PMID- 10937278
TI  - Criteria for demonstrating postcopulatory female choice.

PMID- 10937279
TI  - Distinguishing between female sperm choice versus male sperm competition: a
      comment on Birkhead.

PMID- 10937280
TI  - Criteria for demonstrating female sperm choice.

PMID- 10937281
TI  - Defining and demonstrating postcopulatory female choice--again.

PMID- 10937282
TI  - Evolutionary flexibility and flowering plant familial diversity: a comment on
      Dodd, Silvertown, and Chase.

PMID- 10937284
TI  - Emerging targeting concepts membrane-associated protein thiol-disulfide
      interchange activity: a potential target for anti-viral and anti-tumor drug
      design.

PMID- 10937283
TI  - "Flexibility" as a trait and methodological issues in species diversity variation
      among angiosperm families.

PMID- 10937286
TI  - Enhancement of topical delivery of a lipophilic drug from charged multilamellar
      liposomes.
AB  - To enhance the topical delivery of rhodamine B base (Rho), a model lipophilic
      compound, the electrostatic interaction between the positive and negative
      components incorporated in the liposomal bilayer was utilized. The higher in
      vitro permeability to Rho in rat skin was observed with positive and neutral
      multilamellar liposomal preparations, the former was prepared with
      phosphatidylcholine (PC) and stearylamine (SA) and the latter with PC alone, than
      that given as a solution. Negative liposome composed of PC and dicetyl phosphate
      (DCP) showed lower skin permeability to Rho. To enhance the Rho retention in the
      skin, the electrostatic interaction between SA and DCP, which was confirmed by in
      vitro partition study, was utilized. By pretreating the skin surface with SA
      solution or empty SA liposome, the skin distribution of Rho given as DCP liposome
      was substantially enhanced, with increase in the PC distribution into the skin.
      The pretreatment effect of empty SA liposome was also observed in rats in vivo.
      In conclusion, it was found that negative DCP liposome provides better drug
      retention in the skin with lower skin permeability, and the topical drug delivery
      from DCP liposome was further enhanced by the pretreatment of the skin surface
      with empty SA liposome.

PMID- 10937285
TI  - Poly(amidoamine)s as potential endosomolytic polymers: evaluation in vitro and
      body distribution in normal and tumour-bearing animals.
AB  - Fusogenic peptides derived from viral coat proteins cause perturbation of the
      endosomal membrane and are often used to improve the transfection efficiency of
      non-viral vectors in vitro. However, fusogenic peptides have limited potential
      for use in vivo due to their inherent immunogenicity. Totally synthetic polymers
      that are endosomolytic should circumvent this problem and could be useful as
      components of non-viral delivery systems as long as they do not immediately
      localise in the liver after intravenous (i.v.) injection. Linear poly(amidoamine)
      polymers (PAAs) having amido- and tertiary amino-groups along the main polymer
      undergo pH-dependent conformational change and thus provide an ideal opportunity
      for design of polymers that display membrane activity at low pH. Here we describe
      four PAAs, ISA 1 (Mn = 6900 Da) and ISA 23 (Mn = 10,500 Da) and their analogues
      ISA 4 and ISA 22 (Mn approximately 8000 Da) containing approximately 1 mol% 2-p
      hydroxyphenyl ethylamine to allow radioiodination and thus monitoring of their
      biodistribution. In vitro cytotoxicity was assessed by MTT assay after incubation
      of PAAs with B16F10 and Mewo cell lines. The IC50 values observed for all PAAs
      were > 2 mg/mL in comparison with poly(L-lysine) which displayed an IC50 in the
      range 0.01-0.1 mg/mL. At pH 7.4 none of the PAAs studied was haemolytic at 1 h at
      concentrations below 3 mg/mL. PAAs were subsequently incubated with rat red blood
      cells for 24 h (1 mg/mL) at different pHs. In contrast to poly(L-lysine) which
      was haemolytic at pH 7.4, 6.5 and 5.5, none of the PAAs was lytic at pH 7.4, but
      they became membrane active at lower pH (approximately 45% for ISA 4, 50% for ISA
      22 and 90% for ISA 23). These observations were substantiated by SEM and confirm
      the pH-dependence of membrane activity. After i.v. injection to rats 125I
      labelled ISA 4 was immediately taken up by the liver (> 80% recovered dose at 1
      h) whereas 125I-labelled ISA 22 was not (liver uptake was < 10% recovered dose at
      5 h). Furthermore, biodistribution studies in mice bearing subcutaneous B16F10
      melanoma showed that 125I-labelled ISA 22 was still accumulating in tumour tissue
      after 5 h (2.5% dose/g). PAAs have potential as endosomolytic agents and
      quantitation of the endosome to cytoplasm transfer is warranted after i.v.
      administration.

PMID- 10937287
TI  - Bioavailability of a small unilamellar low-clearance liposomal amikacin
      formulation after extravascular administration.
AB  - Amikacin in small, low-clearance liposomes (MiKasome) has prolonged plasma and
      tissue residence and in vivo activity against extracellular infections, including
      Klebsiella pneumonia and Pseudomonas endocarditis. Small liposomes may cross
      endothelial barriers, and enter the systemic circulation after extravascular
      administration. We compared the systemic bioavailability (F) of low-clearance
      liposomal amikacin in rats following intravenous (i.v.), intraperitoneal (i.p.),
      intramuscular (i.m.) and subcutaneous (s.c.) injection (20 mg/kg) and
      intratracheal (i.t.) instillation (10 mg/kg). Drug-containing liposomes were
      extensively absorbed after i.p. (F = 87-146%) and i.t. (F = 64%) administration,
      with maximum amikacin plasma concentrations of 171 micrograms/ml at 9 h and 80
      micrograms/ml at 18 h, respectively. Absorption was slower and less extensive
      following s.c. (plasma Tmax: 20.3 micrograms/ml at 48 h) and i.m. (plasma Tmax:
      49.6 micrograms/ml at 19 h) injection, but a significant fraction (12-27%) of the
      liposomes was absorbed. The plasma AUCs of liposomal amikacin exceeded the AUC of
      conventional i.v. amikacin by at least 25-fold for all routes. Amikacin AUCs in
      regional lymph nodes exceeded plasma AUCs by 4-fold after s.c. and i.m. injection
      of liposomal amikacin. AUCs in tissues surrounding the injection sites were 20-
      and 191-fold higher than plasma AUCs after i.m. and s.c. injection, respectively.
      Thus, small low-clearance liposomes produced sustained levels of liposome
      encapsulated amikacin in plasma, local tissues and lymph nodes after
      extravascular administration, suggesting applications in perioperative
      prophylaxis, pneumonias and intralesional therapy as well as sustained systemic
      delivery of encapsulated drugs.

PMID- 10937288
TI  - Assessment of targeting potential of galactosylated and mannosylated sterically
      stabilized liposomes to different cell types of mouse liver.
AB  - Galactose and Mannose residues were tagged on the surface of n-glutaryl
      phosphatidylethanolamine (NGPE) containing liposomes with and without
      polyethylene glycol of molecular weight 2000 Da conjugated to distearoyl
      phosphatidylethanolamine (PEG-2000-DSPE). Biodistribution studies showed that
      sugar bearing liposomes were cleared more rapidly from circulation than those not
      bearing the sugar moieties. However, the rate of clearance of glycosylated
      conventional liposomes was much faster than the sugar bearing sterically
      stabilized liposomes. Intrahepatic distribution studies showed that a substantial
      amount of conventional liposomes without sugar residues were taken up by both
      parenchymal (P) (40%) and non-parenchymal (NP) cells (60%). However,
      incorporation of PEG-2000-DSPE shifted this uptake slightly in favour of
      parenchymal cells (47%). While ratio of distribution of galactosylated
      conventional liposomes to P and NP cells was found to be 74:26, galactosylation
      of sterically stabilized liposomes further enhanced the affinity of these
      vesicles towards P cells (P:NP ratio being 93:7). Thus, reduced uptake by Kupffer
      cells was observed with galactosylated sterically stabilized liposomes as
      compared to conventional liposomes. Whereas, mannosylation of both the liposomes
      shifted the distribution towards Kupffer cells in an analogous manner. These
      findings indicate that sterically stabilized liposomes tagged with galactose
      residues on their surface are more effective in targeting the entrapped material
      to hepatocytes as compared to conventional liposomes. This approach can therefore
      be employed for delivering therapeutic agents like drugs, enzymes, genetic
      materials, anti-sense oligonucleotides selectively to liver P cells for treatment
      of hepatic disorders.

PMID- 10937289
TI  - Technology to obtain sustained release characteristics of drugs after delivered
      to the colon.
AB  - To determine the necessary technology by which sustained drug release is obtained
      after drug is delivered to the colon, two kinds of microcapsules were prepared
      and were filled in a pressure-controlled colon delivery capsule (PCDC). As a
      model drug 5-aminosalicylic acid (5-ASA) was used, because the target site of 5
      ASA is the entire large intestine. 5-ASA was microencapsulated using a water
      insoluble polymer, ethylcellulose (EC) or with pH-sensitive polymers, Eudragit L
      100 or S-100 and encased in PCDC. The particle size of these microcapsules was
      around 800 microns and the loading efficiencies of 5-ASA were approximately 90%.
      In vitro dissolution tests were performed with the prepared microcapsules. The
      release rate of 5-ASA from the microcapsules was significantly prolonged as
      compared to 5-ASA powder, although there were no significant differences in the
      release rates between these microcapsules. By incorporating the 5-ASA
      microcapsules into PCDC, sustained release PCDCs for colon delivery were prepared
      and in vivo evaluation was performed using beagle dogs. As a fast release colon
      delivery system, PCDCs were prepared with 5-ASA powder suspended in suppository
      base. After oral administration of the test preparations to beagle dogs, plasma 5
      ASA concentrations were measured and sustained release characteristics of 5-ASA
      from the test preparations were evaluated from the plasma 5-ASA concentration
      time profiles. The first appearance time of 5-ASA into the systemic circulation
      after oral administration were 3 h for all the colon delivery preparations and it
      was thought that these test preparations were delivered to the colon. Both EC
      microcapsules and Eudragit S-100/RS-100 microcapsules in PCDC showed longer the
      mean residence time MRT, 8.2 +/- 0.6 h and 8.7 +/- 0.9 h, than Eudragit L-100/RS
      100 microcapsules in PCDC where the MRT was 6.6 +/- 0.2 h. Since PCDCs containing
      5-ASA powder exhibited a MRT of 7.0 +/- 1.0 h, these two types of preparations
      have suggested sustained release characteristics.

PMID- 10937290
TI  - Preparation and evaluation of once-a-day injectable microspheres of interferon
      alpha in rats.
AB  - Gelatin microspheres (ms) and gelatin/BSA (bovine serum albumin) or
      gelatin/alginate ms were prepared by encapsulating fluorescein isothiocyanate
      (FITC) labeled dextran or interferon alpha (IFN-alpha). Ms were obtained by an
      emulsion-solvent-extraction method. Gelatin and gelatin/BSA ms were obtained by
      treating water-in-oil (W/O) emulsions with iso-propyl alcohol. Gelatin/alginate
      ms having different composition (25/1, 20/1, 15/1, 10/1 and 5/1) were obtained by
      treating a W/O emulsion composed of gelatin and sodium alginate with 0.5 M
      calcium chloride solution. The average diameters of all the prepared ms were
      approximately 300 microns. The FITC-dextran loading efficiencies were 96.5 +/-
      0.6% for gelatin ms (#1), 97.3 +/- 2.2% for gelatin/BSA ms (#2) and 68.7 +/-
      2.2%, 55.0 +/- 3.9%, 47.5 +/- 3.3%, 44.4 +/- 1.2%, 27.1 +/- 2.2% for
      gelatin/alginate ms (#3-#7). The IFN-alpha loading efficiencies were 10.8 +/-
      0.5% for gelatin/BSA ms (#8) and 22.5 +/- 1.8%, 17.6 +/- 0.9% and 14.5 +/- 0.5%
      for gelatin/alginate ms (#9, #10 and #11). In vitro release studies with ms
      containing FITC-dextran showed that the release rate of FITC-dextran from the ms
      decreased by the modification of gelatin ms with BSA or sodium alginate, although
      the effect of BSA addition to gelatin ms did not elucidate satisfactory sustained
      release characteristics of FITC-dextran after subcutaneous (s.c.) injection to
      rats. By decreasing the formulated ratio of gelatin/alginate from 25/1 to 5/1,
      the mean T50%, the time when the half amount of FITC-dextran contained was
      released from the ms, increased from 1.7 +/- 0.1 to 13.8 +/- 3.6 h and three ms
      preparations (#4, #5 and #6) showed sustained-release characteristics on the
      serum FITC-dextran concentration-time profiles. Based on these results, three
      types of ms containing IFN-alpha were prepared and in vivo pharmacokinetic
      studies were performed in rats, where the dose of IFN-alpha was 2 x 10(4) IU/rat.
      By the addition of alginate to gelatin, the release rate of IFN-alpha was
      decreased and the serum IFN-alpha concentration-time profiles showed better
      sustained-release characteristics of IFN-alpha from #10 ms than the other IFN
      alpha ms (#8, #9 and #11) after s.c. injection to rats.

PMID- 10937292
TI  - Language problems in poor readers.
AB  - In recent definitions of dyslexia there is agreement on the following: dyslexia
      is a language (-based) disorder restricted to difficulties in phonological
      processing abilities. This causes primary problems in word decoding and spelling,
      and, as a consequence, also in reading comprehension. This is in accordance with
      the widely accepted reading model, which regards decoding as a prerequisite for
      reading comprehension. In this paper, we will discuss the relevance of these
      definitions, and the reading model they are based on, using data from a
      longitudinal study of readers who were diagnosed as being language-impaired when
      they were pre-schoolers. This group will be compared with a control group having
      no history of language impairments and also with groups of adolescent and adult
      dyslexics.

PMID- 10937291
TI  - The relationship between language and reading. Preliminary results from a
      longitudinal investigation.
AB  - This longitudinal study investigated the relationship between language and
      reading from three perspectives. First, we examined the reading and writing
      outcomes of children identified with spoken language impairments (LIs). Second,
      the early language abilities of children identified as poor readers were
      investigated. Finally, reading and language abilities were treated as continuous
      variables and the developmental relationship between them was studied. In
      general, the results indicated that language abilities (both phonological
      processing and oral language) significantly contributed to achievement in the
      early stages of reading (2nd grade) and had an even stronger effect as children
      acquired greater reading proficiency (4th grade).

PMID- 10937293
TI  - Discourse level writing in dyslexics--methods, results, and implications for
      diagnosis.
AB  - In this paper, we investigate some aspects of the written language production
      process in dyslexic writers. A group of adult dyslexic writers are compared with
      a control group and a group of congenitally deaf writers. We present analyses of
      the actions of both constructing and editing linguistic units during on-line
      writing. The results suggest that in order to understand the organization of how
      linguistic units are constructed in writing, we need to take both cognitive and
      socio-communicative factors into account. We must also recognize that on-line
      recordings could contribute important data in the diagnosis of writing
      difficulties. We propose that the temporal distribution, pause frequencies and
      nested editings on the word level are good candidates for such a diagnostic
      purpose.

PMID- 10937294
TI  - The role of analogies in learning to read.
AB  - A number of factors contribute to proficient word recognition, including
      phonological awareness and the ability to make orthographic analogies. The
      present study considered the relative contribution analogy abilities make toward
      early reading ability. Two analogy tasks and measures of phonological awareness,
      orthographic knowledge, visual memory, general language ability, and non-verbal
      intelligence were administered to 20 second grade good readers and 20 third and
      fourth grade poor readers. The analogy tasks did make a significant contribution
      to early reading ability; however, the analogy tasks were not very different from
      the measures of reading they predicted. In other words, it seems difficult to
      isolate the use of analogies from basic phonological decoding abilities.

PMID- 10937295
TI  - Naming speed, phonological awareness and the initial stage of learning to read.
AB  - Phonological awareness in kindergarten and rapid naming of objects in Grade 1
      were used as predictors of reading achievement in Grade 1. Two reading measures
      were used: oral decoding of both words and pseudowords. They were found to be
      highly correlated. Both rapid naming and phonological awareness accounted for
      independent variance in reading achievement except for pseudoword reading, where
      rapid naming did not contribute significantly after the effect of phonemic
      awareness had been accounted for. Phonological awareness was the stronger
      predictor and a large part of the variance was shared between it and rapid
      naming. The rapid naming testing procedure functioned well and its potential as a
      research and diagnostic tool is discussed.

PMID- 10937296
TI  - Impact of a multi-method promotional package on awareness and knowledge about STD
      and AIDS among the trainees of an industrial training institute in a resettlement
      colony of Delhi, India.
AB  - To design and apply a multi-method promotional package for enhancing awareness
      and knowledge on STD and AIDS among ITI trainees, and evaluate its impact, an
      intervention study, using pre and post assessment of the subjects for comparison
      was carried out. The study was carried out in the Industrial Training Institute
      (ITI), in a resettlement colony of Delhi. Urethral/vaginal discharge, genital
      ulcer and pain on micturition were identified as symptoms of STD by a
      significantly higher number of respondents in the post package sample. A sizable
      number of subjects included inguinal swelling and lower abdominal pain also as
      STD symptoms. The IEC intervention showed a significant improvement in knowledge
      about all four major routes of transmission of HIV/AIDS. Using condoms and
      avoiding sex with Commercial Sex Workers were reported as measures to prevent
      STD/AIDS by a significantly higher number of subjects after the intervention. A
      sizable number of subjects also included other measures (using safe blood/not
      sharing needles etc.) as well. There was a significant decline in the subjects
      preferring self treatment or treatment from a chemist shop in case one suffered
      with an STD. A significant increase was observed in those preferring treatment
      from govt. facilities or private allopathic doctors. However, the intervention
      did not seem to result in preference for alternative systems of medicine. The
      study demonstrated that exposure to intensive promotional intervention, even for
      a brief period can significantly raise awareness and knowledge of young people
      even on sensitive topics like STD and AIDS.

PMID- 10937297
TI  - AIDS-related apprehensions among nursing students of Delhi.
AB  - Students from a nursing school of Delhi were surveyed anonymously using a self
      administered questionnaire to explore various AIDS-related apprehensions and
      their possible reasons. The observations revealed that, majority of the students
      and their families/friends feared that these students were at risk of contracting
      HIV infection while providing routine patient care. A large number of students
      also opined that they would feel uncomfortable while talking, hugging, shaking
      hands, and sharing a room with an HIV positive person. The main reasons for their
      apprehensions were unsatisfactory anti-AIDS campaigning by the government, non
      availability of sufficient protective measures in the health care settings,
      inadequate professional education related to prevention of HIV infection, and
      increase in HIV transmission following false sense of security due to excessive
      condom promotion. Findings of the study imply imparting factual knowledge
      addressing the concerns and removing misconceptions which influence attitudes and
      willingness of the nursing students to provide care to the HIV positives/AIDS
      patients, facts regarding efficacy of various preventive measures, and provision
      of counselling services in the event of exposure.

PMID- 10937298
TI  - Community based study of reproductive tract infections among ever married women
      of reproductive age in a rural area of Haryana, India.
AB  - A community based study was carried out to estimate the load of reproductive
      tract infections (RTIs) among ever married rural women aged 15-44 years and
      utilisation of a mobile village based treatment facility by them, during 1997.
      Complete household survey was done in 10 randomly selected villages of
      Mahindergarh district in Haryana, India. A total of 2325 women were interviewed
      by auxiliary nurse midwives and were invited for medical examination in a health
      camp set-up in their village. Sixty-one percent (1415/2325) women reported
      symptoms of RTIs. Only 35% (812/2325) had their per-speculum examination done.
      Out of those examined, 32% (263/812) had vaginitis, 21% (175/812) had cervicits,
      and 19% (156/812) had pelvic inflammatory disease. Vaginal smear of those having
      discharge revealed that 48% (231/476) had bacterial vaginosis, 0.8% (4/476) had
      fungal infection 9% (44/496) had trichomonal infection and none was found to be
      having gonococcal infection. Tests for chlamydial infection could not be
      performed as the cost was not affordable. Eighty-nine percent of women who
      reported symptoms of RTIs had not consulted anyone for their problem prior to our
      village based camp. Only 42% symptomatic and 24% asymptomatics availed the
      services even in the village based camps. Study revealed high load of
      reproductive tract infections and low utilisation of treatment facility. In-depth
      studies are required to understand for high RTI morbidity load and low treatment
      seeking rate so as to design an appropriate RTI control programme.

PMID- 10937299
TI  - Post-exposure prophylaxis with purified vero cell rabies vaccine during pregnancy
      -safety and immunogenicity.
AB  - This study was conducted with the main objective of determining the safety and
      immunogenicity of purified vero cell rabies vaccine (PVRV) during pregnancy.
      Twenty nine pregnant women exposed to rabies were vaccinated with PVRV as per the
      Essen regimen advocated by World Health Organization. None of the women
      experienced any adverse side effects to the vaccine. The intrauterine growth and
      development monitored by ultrasound examination was found to be normal and the
      outcome of pregnancy was satisfactory. There were no congenital anomalies in any
      of the infants born and they were healthy and had normal growth and development
      during the one year follow-up period. The rabies neutralizing antibody titers
      from day 14 to day 365 following vaccination in these women was adequate and well
      above the minimum protective level of 0.5 iu/ml of serum. Protective levels of
      antibodies were also present in serum of some of the babies tested, for up to 3
      months of age. The mothers and infants followed for one year period were doing
      well at the end of the study period. Consequently, PVRV was found safe and
      immunogenically efficacious during pregnancy.

PMID- 10937301
TI  - Field evaluation of herbal mosquito repellents.
AB  - Repellent properties of Zanthoxylum armatum DC. Syn. Z. alatum Roxb. (Timur),
      Curcuma aromatica (Jungli haldi) and Azadirachta indica (Neem) oils were
      evaluated against mosquitoes in mustard (Brassica sp.) and coconut (Cocos sp.)
      oil base and compared with synthetic repellent. Dimethyl phthalate (DMP) as
      standard. Timur and jungli haldi afforded better protection in the both the base
      at all the concentrations. Tepellents in mustard oil gave longer protection time
      than those in coconut oil. At 0.57 mg/cm2 concentration timur oil gave
      significantly higher protection both in mustard (445 min) as well as coconut oil
      (404 min) than the other repellents and DMP.

PMID- 10937300
TI  - Incidence of HTLV-I in high-risk population in Delhi.
AB  - Human infection due to HTLV-I occurs by transmission of infected T-cells via
      sexual intercourse, blood transfusion or breastfeeding. The present investigation
      was carried out to find the incidence of HTLV-I in high risk population and its
      relationship with syphilis and HIV infection. The study group comprised 124
      antenatal cases, 9 patients attending Sexually Transmitted Disease (STD) clinics
      and 144 blood donors. Passive particle agglutination test was performed on all
      the test sera for anti HTLV-I antibodies. VDRL and Treponema pallidum
      haemagglutination tests were carried out on sera from antenatal and STD cases.
      Sera from blood donors were tested for HIV antibodies by ELISA and confirmed by
      Western Blot. Anti HTLV-I antibodies were found in 10.6% of the cases studied.
      There was no association between the presence of anti HTLV-I antibodies and
      syphilis in expectant mothers and STD cases. However, significant association was
      found between the former and HIV infection in blood donors.

PMID- 10937302
TI  - Knowledge, attitudes and practices of newly diagnosed sputum positive cases of
      pulmonary tuberculosis.
AB  - Lack of awareness of risk posed to the community by a sputum positive case of
      Pulmonary Tuberculosis (PTB) is an impediment in the control of Tuberculosis. A
      study involving 212 newly diagnosed sputum positive patients aged 15 years or
      more, revealed that only 9% of the patients knew correctly the cause of PTB.
      Knowledge about mode of spread of the disease was not known to 49% of patients.
      Awareness regarding the investigations like chest X-ray and sputum examination
      was high as 70% but utility of sputum examination was known to only 29% of the
      patients. Awareness of harmful sequelae of inadequate and incomplete treatment
      was as high as 93% but knowledge per se of adequate duration of treatment was
      poor in a half (50%) of the subjects. Attitude towards domiciliary treatment was
      generally positive (88%) Practices regarding safe sputum disposal and preventive
      measures practised in the families were poor in nearly two third's of patients.
      Health education efforts need to be strengthened to create better awareness of
      these important aspects of tuberculosis diagnosis, treatment and control.

PMID- 10937304
TI  - Effects of elevated temperature and lower pH on infectivity of Leishmania
      donovani promastigotes.

PMID- 10937303
TI  - Nosocomial infection by Salmonella senftenberg in post cardiac surgery patients.

PMID- 10937305
TI  - LD body-negative bone marrow cases of kala-azar in Dharan, Nepal.

PMID- 10937306
TI  - Quinolone resistant typhoid outbreak in an extended joint family.

PMID- 10937307
TI  - Capillaria hepatica, a parasite of zoonotic importance--a brief overview.
AB  - This review briefly elucidates the biology and mode of transmission of the
      parasite capillaria hepatica, an cuimial parasite. Occasional transmitted to man.

PMID- 10937308
TI  - How the quality of third parties' settlement solutions is affected by the
      relationship between negotiators.
AB  - Observers watched videotapes of people negotiating. In half of the videotapes,
      the negotiators had a negative relationship; in the other half, the negotiators
      had a positive relationship. Some observers believed that the relationship was a
      genuine reflection of how the parties felt about one another; others were told
      that the behavior of negotiators was strategic (i.e., used by parties to gain
      advantage). Following the tape, observers recommended a settlement. Observers'
      suggestions were most efficient when the negotiators' relationship was positive
      and genuine; observers proposed significantly worse solutions when negotiators'
      relationships were negative and genuine. The authors advise mediators to focus on
      the issues rather than the emotional tone and to avoid the correspondence bias
      when observing conflicts among parties with negative relationships.

PMID- 10937309
TI  - Pitch and pitch change interact in auditory displays.
AB  - Designing auditory displays requires understanding how different attributes of
      sound are processed. Operators must often listen to a particular stimulus
      dimension and make control actions contingent on the auditory information. Three
      experiments used a selective-listening paradigm to examine interactions between
      auditory dimensions. Participants were instructed to attend to either relative
      pitch or direction of pitch change of dynamic stimuli. With vertically arranged
      keypress responses, reactions to both dimensions showed stimulus-response
      compatibility effects, indicating that pitch is treated spatially. Direction of
      pitch change affected responses to pitch; level of pitch more strongly affected
      responses to pitch change. To reduce deleterious effects of irrelevant pitch
      information, auditory display designers can restrict the pitch range used to
      display dynamic data.

PMID- 10937310
TI  - Effects of verbal and spatial-imagery tasks on eye fixations while driving.
AB  - The consequences of performing verbal and spatial-imagery tasks on visual search
      when driving were studied. Twelve participants drove 84 km on 2 highways and 2
      roads. On each route, they performed 2 verbal tasks and 2 spatial-imagery tasks
      while their eye movements were recorded. The same results were repeated on all
      routes. Pupillary dilation indicated similar effort for each task. Visual
      functional-field size decreased horizontally and vertically, particularly for
      spatial-imagery tasks. Compared with ordinary driving, fixations were longer
      during the spatial-imagery task. With regard to driving performance, glance
      frequency at mirrors and speedometer decreased during the spatial-imagery task.
      Results are interpreted in terms of multiple attention-resource theories;
      implications of internal distractions on road safety are discussed in terms of
      possible impairment in relevant information processing.

PMID- 10937311
TI  - Adaptive automation, trust, and self-confidence in fault management of time
      critical tasks.
AB  - An experiment on adaptive automation is described. Reliability of automated fault
      diagnosis, mode of fault management (manual vs. automated), and fault dynamics
      affect variables including root mean square error, avoidance of accidents and
      false shutdowns, subjective trust in the system, and operator self-confidence.
      Results are discussed in relation to levels of automation, models of trust and
      self-confidence, and theories of human-machine function allocation. Trust in
      automation but not self-confidence was strongly affected by automation
      reliability. Operators controlled a continuous process with difficulty only while
      performing fault management but could prevent unnecessary shutdowns. Final
      authority for decisions and action must be allocated to automation in time
      critical situations.

PMID- 10937312
TI  - Effects of sleep loss on confidence-accuracy relationships for reasoning and
      eyewitness memory.
AB  - Participants (n = 48) deprived of sleep for 29-50 hr, in comparison with controls
      (n = 45), underestimated their performance on logical reasoning and Raven's
      matrices. Such caution may ameliorate adverse practical consequences of sleep
      loss. In contrast, although sleep loss participants were more suggestible on the
      Gudjonsson Suggestibility Scale (G. H. Gudjonsson, 1984, 1987), they maintained
      confidence in their suggestible responses and were inaccurate when responding
      with the highest rating of confidence. This indicates that the increased
      suggestibility is internalized and is due to a cognitive deficit rather than to
      compliance. Eyewitness confidence-accuracy correlations were low but usually
      significant and were lowest after 47-50 hr of sleep loss. Repetition of leading
      questions led to increases in confidence for suggestible responses (with no
      interaction with sleep loss) but not for nonsuggestible responses, indicating a
      problem for jurors' evaluations of practiced testimony.

PMID- 10937313
TI  - Children's use of anatomically detailed dolls to report genital touching in a
      medical examination: developmental and gender comparisons.
AB  - The influence of anatomically detailed dolls on 3- and 4-year-old children's
      reports of a routine medical exam was examined. During the exam, half the
      children received a genital examination and half the children did not.
      Immediately after the exam, all children were asked to demonstrate various events
      on an anatomically detailed doll and on their own bodies. Although there were age
      differences in the number of accurate demonstrations of how the doctor used
      different instruments, there were no age differences on measures that assessed
      reports of genital touching. Among girls, commission errors were more frequent
      when dolls were used because some children falsely showed insertions into the
      anal or genital cavity. The authors conclude that dolls should not be used in
      interviews with children below the age of 5 years.

PMID- 10937314
TI  - Be careful what you ask for: the effect of anchors on personal injury damages
      awards.
AB  - These studies examined the effects of anchors in the context of personal injury
      damages awards. In 2 experiments, mock jurors read a case in which the presence
      and size of the plaintiff's damages request and the defense rebuttal were varied
      across conditions and then awarded damages. Award size and variability increased
      as the plaintiff's request increased but decreased with the most extreme request.
      Conversely, award size and variability decreased as the defense rebuttal
      decreased but increased with the most extreme rebuttal. In both studies, the
      award recommendations altered the upper and lower boundaries of awards mock
      jurors found acceptable but did not affect mock jurors' perception of injury
      severity. The findings suggest that award recommendations can produce biased and
      unpredictable awards.

PMID- 10937316
TI  - The name game: using retrieval practice to improve the learning of names.
AB  - In medium-sized groups such as classes, it is often desirable that the members
      become acquainted with one another. Toward this end, various methods of
      introducing group members are often used, with only anecdotal evidence for their
      effectiveness. The name game is a method for introducing group members that is
      based on the principles of retrieval practice. The authors compared 2 versions of
      the name game with a widely used introductory method--pairwise introductions--and
      found that the name game participants were much better at remembering one
      another's name after 30 min, 2 weeks, and 11 months. A second experiment tested
      the contribution of retrieval practice by comparing 2 versions of the name game
      with a procedure that was matched for number of repetitions and time spent on the
      task. Again, the name games were superior.

PMID- 10937315
TI  - The dynamics of trust: comparing humans to automation.
AB  - Complex industrial environments involve cooperation between operators and
      automation. The strategies used to allocate tasks to automation are a crucial
      component of that cooperation and are known to be affected by the operators'
      trust in the automation. In 2 simulated process control experiments, the authors
      compared trust in automation with trust in human partners in equivalent
      situations. Experiment 1 found the relationship between trust and task allocation
      to be qualitatively identical, but quantitatively attenuated, for human partners
      as compared with automation. Experiment 2 additionally identified the operators'
      trustworthiness, as they thought it would be perceived by a human partner, as
      crucial to task allocation under human collaboration but not under automation.
      The results imply that human collaboration benefits from calibration of people's
      assessment of how others perceive them.

PMID- 10937317
TI  - The effects of averaging subjective probability estimates between and within
      judges.
AB  - The average probability estimate of J > 1 judges is generally better than its
      components. Two studies test 3 predictions regarding averaging that follow from
      theorems based on a cognitive model of the judges and idealizations of the
      judgment situation. Prediction 1 is that the average of conditionally pairwise
      independent estimates will be highly diagnostic, and Prediction 2 is that the
      average of dependent estimates (differing only by independent error terms) may be
      well calibrated. Prediction 3 contrasts between- and within-subject averaging.
      Results demonstrate the predictions' robustness by showing the extent to which
      they hold as the information conditions depart from the ideal and as J increases.
      Practical consequences are that (a) substantial improvement can be obtained with
      as few as 2-6 judges and (b) the decision maker can estimate the nature of the
      expected improvement by considering the information conditions.

PMID- 10937319
TI  - Route choices, anticipated forgetting, and interface design for on-line reference
      documents.
AB  - Preference and usability are imperfectly correlated when choice among procedures
      depends on anticipating cognitive difficulties. Navigation choices were explored
      by offering 2 routes through an on-line price catalog. The harder route never
      varied, but interface features of the easier route varied across readers. In
      Experiment 1, readers chose the easier route (82% trials) when it was visually
      salient but otherwise preferred the harder route from the active window. This
      suggested that visual factors influenced decisions. Experiment 2 equated visual
      factors, but choice of the easier route fell significantly when it needed an
      activation click. Navigating the harder route increased readers' use of an on
      line notebook (i.e., people more often anticipated forgetting prices while
      reading). People choose easier procedures unless interface design miscues
      anticipated effort. Thus, usability evaluation needs to include factors
      influencing choices among methods.

PMID- 10937318
TI  - Object identification as a function of discriminability and learning
      presentations: the effect of stimulus similarity and canonical frame alignment on
      aircraft identification.
AB  - Aircraft that were relatively similar (homogeneous) and relatively dissimilar
      (heterogeneous) in appearance were studied at orientations either consistent
      (canonical) or inconsistent (noncanonical) with the environmental frame of
      reference. At test, participants' identification performance was measured with
      stimuli rotated to novel orientations within the picture plane. During learning
      and testing, identification of heterogeneous aircraft was better than that of
      homogeneous aircraft. At test, only identification of homogeneous aircraft
      revealed a strong linear degradation of performance as angular disparity between
      the novel test orientations and the original learning orientations increased.
      During learning and testing, identification was better for aircraft studied at
      canonical orientations than for those studied at noncanonical orientations. The
      results are discussed in terms of object identification, aircraft recognition
      training, categorization, mental representations, and visual mental rotation.

PMID- 10937320
TI  - A tetrad test for causal indicators.
AB  - The authors propose a confirmatory tetrad analysis test to distinguish causal
      from effect indicators in structural equation models. The test uses "nested"
      vanishing tetrads that are often implied when comparing causal and effect
      indicator models. The authors present typical models that researchers can use to
      determine the vanishing tetrads for 4 or more variables. They also provide the
      vanishing tetrads for mixtures of causal and effect indicators, for models with
      fewer than 4 indicators per latent variable, or for cases with correlated errors.
      The authors illustrate the test results for several simulation and empirical
      examples and emphasize that their technique is a theory-testing rather than a
      model-generating approach. They also review limitations of the procedure
      including the indistinguishable tetrad equivalent models, the largely unknown
      finite sample behavior of the test statistic, and the inability of any procedure
      to fully validate a model specification.

PMID- 10937321
TI  - Putting the individual back into individual growth curves.
AB  - Scaling of time (age) in latent growth curve (LGC) models has important
      implications for studies of development. When participants begin a study at
      different ages, sample means and covariance-based structural equation modeling
      (SEM) approaches produce biased estimates of the variance of the intercept and
      the covariance between the Intercept and Slope factors. However, individual data
      vector-based SEM approaches produce proper estimates of these parameters that are
      identical to those produced by multilevel modeling (MLM). Scaling of the time
      variable also raises issues regarding the interpretation of within- and between
      persons effects of time that parallel those associated with centering of
      predictor variables in MLM. A numerical example is used to illustrate these
      issues, and an Mx script for fitting individual data vector-based LGC models is
      provided.

PMID- 10937322
TI  - Tests for linkage of multiple cohorts in an accelerated longitudinal design.
AB  - In accelerated longitudinal design, one samples multiple age cohorts and then
      collects longitudinal data on members of each cohort. The aim is to study age
      outcome trajectories over a broad age span during a study of short duration. A
      threat to valid inference is the Age x Cohort interaction effect. S. W.
      Raudenbush and W. S. Chan (1993) developed a test for such interactions in the
      context of 2 cohorts by using a hierarchical model. The current article extends
      this approach to include any number of cohorts. Using the National Youth Survey,
      the authors combine data collected on 7 cohorts over 5 years to approximate
      change in antisocial attitudes between 11 and 21 years of age. They show how to
      test for cohort differences in trajectories, how to calculate the power of the
      test, and how to use graphical procedures to aid understanding. The approach
      allows unbalanced designs and the clustering of participants within families,
      neighborhoods, or other social units.

PMID- 10937323
TI  - Rater bias in psychological research: when is it a problem and what can we do
      about it?
AB  - Rater bias is a substantial source of error in psychological research. Bias
      distorts observed effect sizes beyond the expected level of attenuation due to
      intrarater error, and the impact of bias is not accurately estimated using
      conventional methods of correction for attenuation. Using a model based on
      multivariate generalizability theory, this article illustrates how bias affects
      research results. The model identifies 4 types of bias that may affect findings
      in research using observer ratings, including the biases traditionally termed
      leniency and halo errors. The impact of bias depends on which of 4 classes of
      rating design is used, and formulas are derived for correcting observed effect
      sizes for attenuation (due to bias variance) and inflation (due to bias
      covariance) in each of these classes. The rater bias model suggests procedures
      for researchers seeking to minimize adverse impact of bias on study findings.

PMID- 10937324
TI  - A double bootstrap method to analyze linear models with autoregressive error
      terms.
AB  - A new method for the analysis of linear models that have autoregressive errors is
      proposed. The approach is not only relevant in the behavioral sciences for
      analyzing small-sample time-series intervention models, but it is also
      appropriate for a wide class of small-sample linear model problems in which there
      is interest in inferential statements regarding all regression parameters and
      autoregressive parameters in the model. The methodology includes a double
      application of bootstrap procedures. The 1st application is used to obtain bias
      adjusted estimates of the autoregressive parameters. The 2nd application is used
      to estimate the standard errors of the parameter estimates. Theoretical and Monte
      Carlo results are presented to demonstrate asymptotic and small-sample properties
      of the method; examples that illustrate advantages of the new approach over
      established time-series methods are described.

PMID- 10937325
TI  - Neural network modeling of risk assessment in child protective services.
AB  - The advantages of using neural network methodology for the modeling of complex
      social science data are demonstrated, and neural network analysis is applied to
      Washington State Child Protective Services risk assessment data. Neural network
      modeling of the association between social worker overall assessment of risk and
      the 37 separate risk factors from the State of Washington Risk Assessment Matrix
      is shown to provide case classification results superior to linear or logistic
      multiple regression. The improvement in case prediction and classification
      accuracy is attributed to the superiority of neural networks for modeling
      nonlinear relationships between interacting variables; in this respect the
      mathematical framework of neural networks is a better approximation to the actual
      process of human decision making than linear, main effects regression. The
      implications of this modeling advantage for evaluating social science data within
      the framework of ecological theories are discussed.

PMID- 10937326
TI  - Using IRT to separate measurement bias from true group differences on homogeneous
      and heterogeneous scales: an illustration with the MMPI.
AB  - The authors present a didactic illustration of how item response theory (IRT) can
      be used to separate measurement bias from true group differences on homogeneous
      and heterogeneous scales. Several bias detection methods are illustrated with 12
      unidimensional Minnesota Multiphasic Personality Inventory (MMPI) factor scales
      (Waller, 1999) and the 13 multidimensional MMPI validity and clinical scales. The
      article begins with a brief review of MMPI bias research and nontechnical reviews
      of the 2-parameter logistic model (2-PLM) and several IRT-based methods for bias
      detection. A goal of this article is to demonstrate that homogeneous and
      heterogeneous scales that are composed of biased items do not necessarily yield
      biased test scores. To that end, the authors perform differential item- and test
      functioning analyses on the MMPI factor, validity, and clinical scales using data
      from 511 Blacks and 1,277 Whites from the California Youth Authority.

PMID- 10937327
TI  - On the nature and direction of relationships between constructs and measures.
AB  - Theory development typically focuses on relationships among theoretical
      constructs, placing little emphasis on relationships between constructs and
      measures. In most cases, constructs are treated as causes of their measures.
      However, this causal flow is sometimes reversed, such that measures are viewed as
      causes of constructs. Procedures have been developed to identify and estimate
      models that specify constructs as causes or effects of measures. However, these
      procedures provide little guidance for determining a priori whether constructs
      should be specified as causes or effects of their measures. Moreover, these
      procedures address few of the possible causal structures by which constructs and
      measures may be related. This article develops principles for specifying the
      direction and structure of relationships between constructs and measures. These
      principles are illustrated using examples from psychological, sociological, and
      organizational research.

PMID- 10937328
TI  - Permanency and ephemerality of psychological measures with application to
      organizational commitment.
AB  - The constancy or change of an attribute is important to most substantive areas of
      psychology. During the past decade, 2 independent methodological schools have
      developed statistical models for the depiction of longitudinal research. One,
      which might be called the European school, has created latent state-trait models.
      Alternatively, the American school has formulated models that go by the rubric of
      latent curve analysis or latent growth models. In this article, the authors
      integrate both approaches into a detailed unified latent curve and latent state
      trait model (LC-LSTM) that includes the significant features from both schools.
      From the LC-LSTM framework, the permanency and ephemerality of psychological
      measures are discussed and the concepts of stability and reliability are
      reformulated. In addition, a comprehensive illustration on organization
      commitment is presented.

PMID- 10937329
TI  - Statistical power and optimal design for multisite randomized trials.
AB  - The multisite trial, widely used in mental health research and education, enables
      experimenters to assess the average impact of a treatment across sites, the
      variance of treatment impact across sites, and the moderating effect of site
      characteristics on treatment efficacy. Key design decisions include the sample
      size per site and the number of sites. To consider power implications, this
      article proposes a standardized hierarchical linear model and uses rules of thumb
      similar to those proposed by J. Cohen (1988) for small, medium, and large effect
      sizes and for small, medium, and large treatment-by-site variance. Optimal
      allocation of resources within and between sites as a function of variance
      components and costs at each level are also considered. The approach generalizes
      to quasiexperiments with a similar structure. These ideas are illustrated with
      newly developed software.

PMID- 10937330
TI  - Beyond the Spearman-Brown: a structural approach to maximal reliability.
AB  - The requirement of parallel parts has long been the cornerstone of classic
      reliability theory. By recasting reliability in a structural equation framework,
      items, raters, or judges no longer need to be treated as equivalent entities.
      Instead, unique reliability estimates can be determined for each and collectively
      used to assess the maximal reliability of a weighted composite, with the
      composite reliability submitted to inferential test. Procedures are shown to
      generalize from single to multifactor applications. Ramifications of a structural
      approach to reliability determination are probed, and the dilemma posed by
      possible falsification of the true score hypothesis presented for individual
      researcher consideration.

PMID- 10937331
TI  - Clarification of Cliff and Caruso (1998).
AB  - In response to N. Cliff and J. C. Caruso (1998), the author clarifies that it is
      the sum of the reliabilities of the components that remains invariant under
      rotation in reliable component analysis.

PMID- 10937332
TI  - Testing for robustness in Monte Carlo studies.
AB  - Monte Carlo studies provide the information needed to help researchers select
      appropriate analytical procedures under design conditions in which the underlying
      assumptions of the procedures are not met. In Monte Carlo studies, the 2 errors
      that one could commit involve (a) concluding that a statistical procedure is
      robust when it is not or (b) concluding that it is not robust when it is. In
      previous attempts to apply standard statistical design principles to Monte Carlo
      studies, the less severe of these errors has been wrongly designated the Type I
      error. In this article, a method is presented for controlling the appropriate
      Type I error rate; the determination of the number of iterations required in a
      Monte Carlo study to achieve desired power is described; and a confidence
      interval for a test's true Type I error rate is derived. A robustness criterion
      is also proposed that is a compromise between W. G. Cochran's (1952) and J. V.
      Bradley's (1978) criteria.

PMID- 10937333
TI  - Null hypothesis significance testing: a review of an old and continuing
      controversy.
AB  - Null hypothesis significance testing (NHST) is arguably the most widely used
      approach to hypothesis evaluation among behavioral and social scientists. It is
      also very controversial. A major concern expressed by critics is that such
      testing is misunderstood by many of those who use it. Several other objections to
      its use have also been raised. In this article the author reviews and comments on
      the claimed misunderstandings as well as on other criticisms of the approach, and
      he notes arguments that have been advanced in support of NHST. Alternatives and
      supplements to NHST are considered, as are several related recommendations
      regarding the interpretation of experimental data. The concluding opinion is that
      NHST is easily misunderstood and misused but that when applied with good judgment
      it can be an effective aid to the interpretation of experimental data.

PMID- 10937334
TI  - Management of integrated delivery systems in the next decade.
AB  - In an attempt to find some remedies within what is already a highly competitive
      and politically charged environment, this article's purpose is to specify some
      major steps that the management of integrated delivery systems might heed in the
      next decade to curtail their expenditures and better position themselves for the
      future.

PMID- 10937335
TI  - Globalization of U.S. health care services: assessment and implementation.
AB  - Globalization has become a commonly used term to describe the manner in which
      organizations in many industries have spread their operations and management to
      foreign countries. As the trend toward a global economy progresses, more and more
      industries, including health care, are looking to capitalize on its possible
      benefits. This article examines globalization in other industries and applies the
      tools used elsewhere to U.S. health care organizations.

PMID- 10937336
TI  - How do urban organized health care delivery systems link with rural providers?
AB  - Organized delivery systems are becoming an increasingly important component of
      urban health care markets and are expanding their influence in rural areas as
      well. They also are developing new linkages with rural providers. This article,
      based on the experiences of 20 diverse organizations, identifies and describes
      the strategies being used by urban systems to redefine linkages with rural
      hospitals and, particularly, physicians.

PMID- 10937338
TI  - Surveying hospital network structure in New York State: how are they structured?
AB  - We determine the most common network structures in New York state. The taxonomy
      employed uses three structural dimensions: integration, complexity, and risk
      sharing between organizations. Based on a survey conducted in 1996, the most
      common type of network (26.4 percent) had medium levels of integration, medium or
      high levels of complexity, and some risk-sharing. Also common were networks with
      low levels of integration, low levels of complexity, and no risk-sharing (22.1
      percent).

PMID- 10937337
TI  - Strategies for effective management participation in community health
      partnerships.
AB  - This article develops guidelines for effective health services management
      participation in community health partnerships. Drawing on our study of Community
      Care Network (CCN) Demonstration, the strategic alliance literature, and other
      research, we describe six challenges that health services managers are likely to
      face as partnership participants and discuss the strategies that they might use
      to deal with them.

PMID- 10937339
TI  - Workforce cultural factors in TQM/CQI implementation in hospitals.
AB  - One of the major obstacles to successful implementation of TQM/CQI in hospitals
      has been management's failure to consider the workforce cultural situation. This
      quasi-qualitative study investigates eight workforce cultural factors in seven
      midwestern hospitals. Results reveal only one of the seven hospitals successfully
      implementing TQM/CQI.

PMID- 10937340
TI  - Understanding stakeholder power and influence gaps in a health care organization:
      an empirical study.
AB  - Scholars have vigorously debated the role of stakeholders since Freeman's 1984
      landmark work. This article argues that an accurate assessment of relative power
      levels can enable stakeholders to accept their proper roles and responsibilities
      in planning and implementing strategy and enabling Top Management Teams to more
      fully integrate stakeholders' interest into the planning process.

PMID- 10937341
TI  - [Early malignant changes in ovarian epithelium--the relationship between
      histology and molecular biological change].

PMID- 10937342
TI  - Establishment of a tightly regulated human cell line for the development of
      hepatocyte transplantation.
AB  - Hepatocyte transplantation (HTX) could be an attractive treatment for patients
      with liver failure and liver-based metabolic disease. Human primary hepatocytes
      are ideal in this modality, but the shortage of human livers available for
      hepatocyte isolation severely limits the use of this form of therapy. A tightly
      regulated human hepatocyte cell line that grows economically in culture and
      exhibits differentiated liver functions would be an attractive alternative to the
      primary human hepatocytes. To test the feasibility, human hepatocytes were
      immortalized by a retroviral vector expressing simian virus 40 large T antigen
      and herpes simplex virus-thymidine kinase. A highly differentiated immortal
      hepatocyte line NKNT-3 was established. NKNT-3 cells grew in chemically defined
      serum-free medium, retained highly differentiated liver functions, and were
      sensitivity to ganciclovir as a prodrug. Essentially unlimited availability of
      NKNT-3 cells may be clinically useful for HTX and bioartificial liver.

PMID- 10937343
TI  - Down-regulation of E-cadherin by antisense oligonucleotide enhances basement
      membrane invasion of pancreatic carcinoma cells.
AB  - Pancreatic carcinoma shows a marked invasiveness around tissues lymph node and/or
      hematogenous metastases resulting in poor prognoses of the patients. We examined
      on whether E-cadherin is associated with these malignant behaviors of pancreatic
      carcinoma cells using a human pancreatic adenocarcinoma cell line, JHP-1.
      Immunohistochemically, E-cadherin expression of JHP-1 cells was remarkably
      inhibited by treatment with E-cadherin antisense oligonucleotide. By invasion-MTT
      assay, JHP-1 cells treated with E-cadherin antisense oligonucleotide showed a
      significant increase of invasiveness compared to those treated with the control
      oligonucleotide (P < 0.001), whereas the proliferation of JHP-1 cells was not
      affected by the presence of either E-cadherin antisense or control
      oligonucleotide. Thus, down-regulation of E-cadherin of pancreatic carcinoma
      cells induced the invasiveness into the basement membrane. These results suggest
      that the reduction in E-cadherin expression plays a key role not only in
      detachment of cell-cell adhesion but also in invasion and metastasis of
      pancreatic carcinoma cells.

PMID- 10937344
TI  - Synergistic antiproliferative effect of delta 12-prostaglandin J2 (delta 12-PGJ2)
      and hyperthermia on human esophageal cancer cell lines.
AB  - delta 12-PGJ2, one of the cyclopentenone prostaglandins and the ultimate
      metabolite of prostaglandin D2, has been reported to have potent
      antiproliferative activity on various tumor cells in vitro and in vivo. In this
      study, the combined effect of delta 12-PGJ2 and hyperthermia on six established
      cell lines of human esophageal carcinoma (SGF series) was analyzed by an in vitro
      assay, and the degree of apoptosis induced by this combination was examined to
      clarify the mechanism of supra-additive effects. In five SGF cell lines, except
      SGF-7 cells, combination therapy with delta 12-PGJ2 and hyperthermia showed
      synergistic antiproliferative effects. The supra-additive combined effect of
      delta 12-PGJ2 and hyperthermia on esophageal cancer cells is attributed to the
      synergistic induction of apoptosis. delta 12-PGJ2 induced G1 accumulation and
      apoptosis was induced by delta 12-PGJ2 from G1 phase. Hyperthermia induced G1
      accumulation and apoptosis was induced by hyperthermia during all cell phases.
      Both augmented G1 arrest followed by G1 phase-selective induction of apoptosis
      and increased apoptotic induction without cell-cycle specificity are responsible
      for the synergism of combined treatment with delta 12-PGJ2 and hyperthermia.

PMID- 10937345
TI  - Successful treatment of IBL-like T-cell lymphoma with cyclosporin A: two case
      reports with special reference to serum cytokine levels.
AB  - The prognosis of immunoblastic lymphadenopathy (IBL)-like T-cell lymphoma is
      grave, and its effective treatments have not been established. We applied oral
      cyclosporin A (CsA) treatment to two cases of IBL-like T-cell lymphoma, and
      succeeded in achieving complete remissions. CsA is known to have a suppressive
      effect on the immune system, most notably T-cells, but it also has a direct
      cytotoxic/apoptosis-inducing effect on lymphocytes. Its combined effects on
      neoplastic T-cells might have played an important role in achieving remission. In
      both cases, serum levels of interleukin-12 (IL-12) and tumor necrosis factor
      alpha (TNF-alpha) were elevated and decreased or returned to normal after
      achieving remissions. Considering that both cytokines represent monokines, it
      seems that a macrophage system is also involved in the pathogenesis of this
      disorder. Our two cases indicate that administration of CsA may be an effective
      therapy for IBL-like T-cell lymphoma.

PMID- 10937346
TI  - Human bone marrow stroma-dependent myeloma sister cell lines MOLP-6 and MOLP-7
      derived from a patient with multiple myeloma.
AB  - Human bone marrow stroma (BST)-dependent myeloma sister cell lines MOLP-6 and
      MOLP-7 were established from the peripheral blood of a multiple myeloma (MM)
      patient with IgA kappa type MM (stage IIIB). The growth of the cell lines is
      constitutively dependent on BST cells; none of the cytokines tested nor the
      culture supernatant of the BST cells could support the growth. Both cell lines
      showed typical plasma cell morphology with abundant cytoplasm and one to four
      nuclei under Wright staining. The immunoprofiles of MOLP-6 and MOLP-7 correspond
      to that seen typically in primary MM cells: positive for cytoplasmic
      immunoglobulin (Ig) chains, a heavy and kappa light chains, CD9, CD28, CD40,
      CD44, CD45, CD56, and PCA-1; the cells were negative for surface Igs and various
      other B-cell, T-cell and myelomonocyte associated markers. Both cell lines also
      expressed adhesion molecules including HCAM (CD44), VLA-4 (CD49d/CD29), VLA-6
      (CD49f/CD29), ICAM-1 (CD54), NCAM (CD56), LFA-3 (CD58) and L-selectin (CD62L).
      The doubling time of MOLP-6 and MOLP-7 was 48 and 168 hours, respectively. In
      addition to this growth characteristic, the maximum cell density of each cell
      line was obtained at 1.7 x 10(6) cells/ml and 9.7 x 10(5) cells/ml, respectively.
      The characteristics of each cell line may reflect intraclonal variation of the
      proliferative capacity. The MOLP-6 together with the MOLP-7 sister will be useful
      model systems for the investigation of the biology of myeloma.

PMID- 10937347
TI  - Human papillomavirus types 56 and 59 in novel cervical cancer cell lines.

PMID- 10937348
TI  - Does resveratrol induce pharmacological preconditioning?
AB  - Resveratrol is a grape component with complex pharmacology related to its
      antioxidant activity. Little is known about the direct effects of resveratrol on
      the myocardium. We tested whether resveratrol administration before ischemia
      could attenuate ischemic/reperfusion damage. We examined how resveratrol affects
      high-energy phosphate metabolism (31P-nuclear magnetic resonance) and
      contractility of isolated Langendorff perfused rat hearts subjected to 20 min no
      flow ischemia and 30 min reperfusion. During 10 min resveratrol infusion (10
      microM) before ischemia, basal phosphorylation potential dropped by 40% (p < 0.05
      vs. preinfusion value) without affecting contractility. The level of effluent
      adenosine was increased by 68%, parallel to a 50% increase in coronary flow.
      Resveratrol significantly improved postischemic recovery of rate-pressure product
      (62 +/- 5.2 vs. 23 +/- 8.1% of controls; p < 0.05). The metabolic pattern
      following resveratrol infusion was similar to that produced by ischemic
      preconditioning, suggesting that an increase in adenosine availability is
      involved in cardioprotection.

PMID- 10937349
TI  - Biochemical studies of a natural antioxidant isolated from rosemary and its
      application in cosmetic dermatology.
AB  - Oxidative damage to DNA, RNA, proteins and cell membranes occurs when the
      cellular concentration of reactive oxygen species exceeds the capacity of the
      cell to eliminate them. Aerobic prokaryotic and eukaryotic organisms have
      developed a set of cell defense systems to mitigate the damaging effects of
      reactive oxygen species. Epithelial surfaces contain antioxidants that could be
      expected to provide a defence against environmental stress caused by reactive
      oxygen and nitrogen species. Skin, which has a highly differentiated and complex
      structure, is particularly vulnerable to free radical damage because of its
      contact with oxygen and with other environmental stimuli. Fruit and vegetables
      contain several classes of compounds that when ingested can potentially
      contribute to endogenous modulation of antioxidant defences. The purpose of this
      study was to investigate the effectiveness of a natural extract derived from
      rosemary to protect free radical-induced skin damage. We provide evidence that an
      alcoholic extract of rosemary leaves, Rosm1, is endowed with strong antioxidant
      activity and, as evaluated by both in vitro and in vivo systems, is capable of
      inhibiting oxidative alterations to skin surface lipids. The present study
      provides a preclinical perspective on the interface between the biochemical
      properties of a natural extract isolated from rosemary leaves, a better
      understanding of the endogenous antioxidant potential of skin and the real
      validity of natural antioxidant biotechnology in antiaging skin management.

PMID- 10937350
TI  - Pathomorphological changes in mouse liver and kidney during prolonged valproate
      administration.
AB  - Mice given sodium valproate 0.71% weight/volume in drinking water for 7, 14 and
      21 days were assessed for pathomorphological changes in liver and kidney tissues
      at certain time points. This treatment caused a marked alteration in liver and
      kidney cell morphology, which was proportional to the period of treatment. This
      treatment induced fatty degeneration of hepatocytes, increased the number of
      Kupffer cells and caused them to swell. These changes were irregular after days 7
      and 14 of treatment but with time increased in intensity, producing inflammation
      of the portal tracts, albuminous degeneration and necrosis of septa. Precirrhotic
      conditions, cirrhosis, acidophilic degeneration of hepatocytes and glassy
      eosinophilic homogenous cytoplasm were a constant feature after 21 days'
      treatment. In some cases the portal area was invaded by small, round inflammatory
      cells. Hepatocytes in this group were swollen, with large nuclei and increased
      amounts of condensed chromatin. The kidney sections of the same animals revealed
      severe morphological changes, indicated by significant epithelial necrosis and
      sloughing of tubules, as well as cast formation and mild lymphocytic infiltrate
      after 21 days' treatment. The results suggest that the histopathologic changes
      induced by sodium valproate are dependent upon the duration of exposure of these
      organs to the drug. Prolonged use of this drug should be carefully assessed.

PMID- 10937351
TI  - Tissue changes detectable by sonography before radiological evidence of elbow
      chondrocalcinosis.
AB  - Chondrocalcinosis is a joint disease caused by deposits of calcium pyrophosphate
      dihydrate (CPPD) crystals with manifestations that may include intermittent
      attacks of acute arthritis or enthesitis. If no crystals are found on synovial
      analysis, the diagnosis in clinical practice is based on typical radiographic
      findings, although it is now recognized that some signs of the disease could also
      be seen by ultrasound. We studied six patients with elbow enthesopathy without
      radiographic evidence of CPPD that presented ultrasound findings suggesting joint
      calcification. On the basis of these echographic findings, the diagnosis was then
      ascertained by x-ray examination of the most commonly involved joints. Ultrasound
      is a method of proven interest in the evaluation of rheumatic patients and could
      be an important tool in diagnosing CPPD.

PMID- 10937352
TI  - Scavenger receptor class B type I (SR-BI) and high-density lipoprotein
      metabolism: recent lessons from genetically manipulated mice.
AB  - The scavenger receptor BI is a cell surface lipoprotein receptor for selective
      high-density lipoprotein (HDL) cholesterol uptake in the liver and steroidogenic
      tissues. Studies of genetically manipulated strains of mice have revealed that SR
      BI plays a key role in regulating HDL metabolism, cholesterol transport to
      steroidogenic tissues and bile cholesterol secretion. Furthermore, SR-BI protects
      against the development of atherosclerosis and is required for normal female
      fertility. If SR-BI has similar functions in lipoprotein metabolism and
      atherosclerosis in humans, it may represent a new target for the prevention
      and/or treatment of atherosclerotic cardiovascular disease.

PMID- 10937353
TI  - Role of hepatic and lipoprotein lipase in lipoprotein metabolism and
      atherosclerosis: studies in transgenic and knockout animal models and somatic
      gene transfer.
AB  - Hepatic lipase (HL) and lipoprotein lipase (LPL) are the two major lipolytic
      enzymes responsible for the hydrolysis of triglycerides and phospholipids present
      in circulating plasma lipoproteins. Both lipases are attached to the vascular
      endothelium via cell surface proteoglycans. HL is primarily involved in the
      metabolism of chylomicron remnants, intermediate density lipoproteins and high
      density lipoproteins whereas LPL catalyzes the hydrolysis of triglycerides from
      chylomicrons and very low-density lipoproteins. In addition to their traditional
      function as lipolytic enzymes, HL and LPL appear to serve as ligands that mediate
      the interaction of lipoproteins to cell surface receptors and/or proteoglycans.
      Over the past several years significant advances have been made in our
      understanding of new, alternative mechanisms by which HL and LPL modulate
      lipoprotein metabolism and the development of atherosclerosis in vivo. This
      review will summarize some of the new insights generated from the study of
      transgenic and knockout HL and LPL animal models as well as somatic gene transfer
      of these two lipases.

PMID- 10937354
TI  - Use of transgenic mice to study the role of apolipoprotein E in lipid metabolism
      and atherosclerosis.
AB  - Insight into the role of apolipoprotein (apo) E in lipoprotein metabolism and
      atherosclerosis has increased dramatically with the generation and analysis of
      novel transgenic, knockout and knockin mouse models. Moreover, the recent
      development and application of somatic gene and cell transfer technologies which
      can express (or delete) apoE in specific tissues of virtually any mouse model
      have further added to this increase in knowledge. It is now well established that
      apoE plays a role in virtually every step in the metabolism of very low-density
      lipoproteins and in the efflux of cholesterol from macrophages. In this review we
      will discuss recent insights into the role of apoE in these processes with
      particular emphasis on the specific effects of variation in apoE structure and
      quantity.

PMID- 10937355
TI  - Insights into apolipoprotein C metabolism from transgenic and gene-targeted mice.
AB  - Studies in humans on the in vivo metabolism of apolipoprotein (apo) Cs have been
      hampered by the highly complex nature of lipoprotein metabolism, which can be
      influenced by multiple genetic and environmental factors. In order to gain new
      insights into the function of the individual apoCs in lipoprotein metabolism,
      several laboratories have created mouse models lacking or overexpressing the
      respective APOC genes through the technologies of gene targeting and
      transgenesis. Until now, the only well-established in vivo metabolic function of
      apoC-I has been its inhibitory action on the uptake of very low-density
      lipoprotein (VLDL) via hepatic receptors, particularly the low-density
      lipoprotein (LDL) receptor-related protein. Consequently, the presence of apoC-I
      on the lipoprotein particle may prolong its residence time in the circulation and
      subsequently facilitate its conversion to LDL. ApoC-II, on the other hand, is a
      major activator of lipoprotein lipase, which is required for an efficient
      processing of triglyceride-rich lipoproteins in the circulation. However, an
      excess of apoC-II on the lipoprotein particle has been suggested to inhibit the
      lipoprotein-lipase-mediated hydrolysis of triglycerides. From studies with APOC3
      transgenic and ApoC3-knockout mice, it appears that apoC-III inhibits the
      lipolysis of triglyceride-rich lipoproteins by hampering the interaction of these
      lipoproteins with the heparan sulfate proteoglycan-lipoprotein lipase complex.
      Subsequently, the poorly lipolyzed apoC-III-containing lipoprotein particles may
      accumulate in plasma because of their lower binding affinity towards hepatic
      receptors due to a change in lipid composition, particle size or the presence of
      apoC-III on the particle itself. From these data it can thus be concluded that
      all C apolipoproteins specifically modulate the metabolism of triglyceride-rich
      lipoproteins, which may contribute to the development of hyperlipidemia and other
      lipoprotein abnormalities in humans.

PMID- 10937356
TI  - Cholesterol homeostatic mechanisms in transgenic mice with altered expression of
      apoproteins A-I, A-II and A-IV.
AB  - Our understanding of the in vivo metabolic functions of apoA-I and A-II has
      greatly advanced with the use of transgenic mice, but the physiological role of
      apoA-IV remains elusive. Both apoA-I and A-II are necessary for the structural
      stability of high-density lipoprotein (HDL). Structural differences exist between
      human and mouse A apoproteins because: i) human cholesterol ester transfer
      protein, lecithin cholesterol acyl transferase and phospholipid transfer protein
      interact better with human apoA-I; ii) human apoA-I and A-II, alone or in
      combination, form polydisperse instead of monodisperse HDL particles. Human apoA
      II overexpression has highlighted its inhibitory effect on lipoprotein lipase and
      hepatic lipase, resulting in hypertriglyceridemia and concomitantly decreased HDL
      and apoA-I. After long-term challenge with an atherogenic diet, mice are less
      protected against lesion formation by human apoA-II, mouse apoA-II being overtly
      proatherogenic. On the other hand, human apoA-I confers great protection against
      lesion formation and causes reduction of preexisting lesions. Human apoA-IV is
      also protective, although the mechanisms by which this protection is achieved
      remain to be determined.

PMID- 10937357
TI  - Role of phospholipid transfer protein in high-density lipoprotein metabolism:
      insights from studies in transgenic mice.

PMID- 10937358
TI  - Transgenic mouse models to study the role of the macrophage scavenger receptor
      class A in atherosclerosis.
AB  - Several in vivo studies have been performed on the role of the macrophage
      scavenger receptor class A (SR-A) in atherosclerosis using SR-A knockout mice.
      The results indicate both an antiatherogenic and a proatherogenic role of SR-A,
      depending on the nature of the animal model serving as the athero-susceptible
      background. To study the role of SR-A in a different model, we generated a
      transgenic mouse model with high level expression of the human SR-A gene using a
      180 Kb yeast artificial chromosome (MSR1 transgenic mice). These mice show
      increased expression of SR-A according to the natural expression pattern. The
      MSR1 transgenic mice were crossed onto a low-density lipoprotein receptor
      deficient background and were fed a high fat diet for 10 weeks. After this
      period, the size of the atherosclerotic lesions in the proximal aorta was
      measured. Surprisingly, atherosclerosis was significantly reduced in the MSR1
      transgenic mice. In a second study, the effect of SR-A was examined in APOE-3
      Leiden mice providing a different athero-susceptible background. To exclude
      nonmacrophage effects, bone marrow was transplanted from MSR1 mice and wild-type
      littermates to APOE-3 Leiden transgenic mice. After 8 weeks on a high fat diet,
      atherosclerosis in the mice that had received MSR1 bone marrow was reduced
      compared with mice that had received wild-type bone marrow. This difference
      reached statistical significance when individual cholesterol exposure of the mice
      was taken into account. Both experiments indicated an antiatherogenic role of the
      SR-A. This observation cannot be explained easily by SR-A function in foam cell
      formation because in MSR1 macrophages in vitro foam cell formation is increased.
      Alternatively, however, SR-A may affect the activation of macrophages. Hence the
      response to lipopolysaccharide was measured in MSR1-transgenic macrophages. These
      macrophages showed a reduction in their activation in response to
      lipopolysaccharide, as measured by nitric oxide production. These data show that
      an elevated level of SR-A expression reduces atherosclerosis, potentially by
      modifying the response of macrophages to activation signals in the plaque.

PMID- 10937359
TI  - The development of a computer controlled system to simulate in rats, the rapid,
      frequent changes in oxygen experienced by preterm infants developing retinopathy
      of prematurity.
AB  - Preterm infants that develop severe ROP have significantly more fluctuations in
      their transcutaneous oxygen compared to mild or no ROP, despite the fact that all
      these infants are kept within clinically 'safe' limits. Current animal models do
      not accurately reflect this oxygen environment. Our aim was to custom build
      equipment capable of reproducing the transcutaneous oxygen (TcPO2) levels
      recorded by infant cotside monitoring equipment in a rat model and assess the
      equipment's precision. Using previously published data for the rat that
      translates TcPO2 into the equivalent inspired FiO2, a profile was derived from a
      datalog of TcPO2 values recorded every minute for 14 days in an infant that had
      developed severe ROP. This profile was controlled in the animal chamber by
      software algorithms which calculated the amount and type of gas to be injected to
      move oxygen to each new set-point. CO2 regulation within the chamber was also
      possible. Absolute differences between the datalog set-points (n = 17,465) and
      the oxygen sensor were median 0.3% oxygen, IQR 0.2-0.7% oxygen, with 95% of the
      differences < +/- 2% oxygen. The equipment is capable of reproducing the oxygen
      environment experienced by a preterm ventilated infant, giving a satisfactory
      level of precision.

PMID- 10937360
TI  - Good design practice for medical devices and equipment, Part II: Design for
      validation.
AB  - Medical devices and their associated process equipment must be reliable and fit
      for purpose. In light of the recent changes to the medical device regulations,
      manufacturers must now take an integrated approach to design, development and
      validation. Good design practice encourages this integrated approach while
      ensuring fitness for purpose within commercial reality. A review of current
      literature related to good design practice carried out in Part I of this paper
      showed that there is inadequate guidance regarding the integration of validation
      with design. This paper proposes a practical approach to design for validation
      aimed at making devices easier and more economic to validate. The approach comes
      in the form of a model of design for validation that illustrates the basic
      relationship between design, development and validation and a series of design
      tactics that were formulated in order to help designers take a more proactive
      approach to validation during design.

PMID- 10937361
TI  - Modelling transthoracic defibrillation waveforms.
AB  - Recent investigations connected with implantable defibrillators yielded new data
      on heart electrophysiology, resulting in reassessment of existing and advancing
      of new types of electrical impulses. Different electrical equivalent circuits
      were proposed for modelling intracardiac and transthoracic defibrillation pulse
      waveforms, comprising generator, electrode interface and tissue resistances. We
      attempted modelling of the transmembrane voltage Vm time course, induced by
      different applied voltage Vs waveforms, taking into account only the shapes and
      the relative Vs and Vm amplitudes. The excitable cell membrane impedance Zm was
      modelled with higher resistance and lower capacitance, so that a shunting effect
      on the generator and tissue resistances was avoided. The result was a very simple
      equivalent circuit. We proposed criteria for efficient defibrillation pulse
      waveforms yielding a straightforward approach to model existing and new pulses
      and to assess their efficiency.

PMID- 10937362
TI  - Expert systems in medicine: academic exercise or practical tool?
AB  - From the earliest stages of computer development, scientists have aspired to the
      creation of advanced systems which could simulate human thought and reasoning. Of
      all the modern technological quests, this research to create artificially
      intelligent computer systems has been one of the most ambitious and fascinating.
      Although attempts have been made for the last 30 years to develop and apply such
      systems to the medical sciences, only limited progress has been made. This paper
      reviews and discusses the important role of expert systems in medicine and
      outlines future trends in this area.

PMID- 10937363
TI  - Time-frequency analysis of the heart rate variability during the Valsalva
      manoeuvre.
AB  - We present an analysis of the heart rate variability during the Valsalva
      manoeuvre. The more frequently used time-frequency distributions were applied in
      order to analyse the dynamical behaviour of several spectral indexes during the
      manoeuvre. The influence of the branches of the autonomous system can be
      predicted following the evolution of the studied indexes. The exponential time
      frequency distribution showed the best results in the graphical representation,
      as well as in the indexes calculation. The total power, the low-to-high frequency
      ratio and the fractal dimension were analysed throughout the different phases of
      the manoeuvre and a representative model of these parameters' evolution was
      proposed.

PMID- 10937364
TI  - Two assessments of American usage frequencies for ninety-seven sentence
      complement-taking nouns.
AB  - Two studies documented the American English usage frequencies for ninety-seven
      nouns that occur with sentence complements (e.g., "rumor," "The rumor that the
      student cheated..."). An established usage preference methodology was used (see
      Connine, Ferreira, Jones, Clifton, & Frazier, 1984; Kennison, 1999). In Study 1,
      participants completed short fragments that did not contain the overt
      complementizer "that," as in "The rumor..." In Study 2, participants completed
      short sentence fragments that contained the overt complementizer, as in "The
      rumor that..." The results showed that when the complementizer was absent (Study
      1), bare (i.e., unmodified) usages and prepositional phrase usages were
      frequently observed. In contrast, sentence complement and relative clause usages
      were rarely observed. When the complementizer was present (Study 2), the
      frequency of sentence complement and relative clause usages varied. The estimates
      of usage frequency obtained in these studies are intended to be a resource for
      language comprehension researchers.

PMID- 10937365
TI  - Word-monitoring tasks interact with levels of representation during speech
      comprehension.
AB  - Researchers frequently use data from monitoring tasks to argue that constraints
      on meaning facilitate lower-level processes. An alternate hypothesis is that the
      processing level that a monitoring task requires interacts with discourse-level
      processing. Subjects monitored spoken sentences for a synonym (semantic match), a
      nonsense word (phonological match), or a rhyme (phonologically and semantically
      constrained matching). The critical targets appeared at the beginning of the
      final clause in two-clause sentences that began with if, which signals a semantic
      analysis at the discourse level, or with though, which maintains a surface
      representation. Synonym-monitoring times were faster for if than for though,
      nonsense word-monitoring times were faster for though than for if, and rhyme
      monitoring times did not differ for if and though. The results show that
      conjunctions influence how listeners allocate attention to semantic versus
      phonological information, implying that listeners form these kinds of information
      independently.

PMID- 10937366
TI  - Irony as a game of implicitness: acoustic profiles of ironic communication.
AB  - Irony, as "quotation" and "fencing game," consists of an interactive script,
      grounded on a focal event "trigger," in which the dialogic comment shows the
      ironist's intention through an antiphrastic process and syncoding to "hit" the
      victim of the irony (blame by praise or praise by blame). Through acoustic
      analysis of the suprasegmental profiles of standard phrases inserted into
      inductors expressly composed and read by 50 naive subjects, the presence and
      nature of significant differences between sarcastic and kind irony in low- and
      high-context utterances (contextualization effect--Experiments 1 and 2) have been
      verified. It has also been observed that, where more "specific weight" is given
      to the linguistic stream (corrective irony hypothesis), a markedness of
      suprasegmental features emerges (correctivity effect--Experiment 3). Finally,
      comparison between sarcastic irony and blame and between kind irony and praise
      shows that there exists a precise manner of contrastive syncoding, whereby the
      voices of irony do not coincide with those of direct blame or praise, but assume
      a specific caricature and emphatic profile (contrastivity effect--Experiment 4).

PMID- 10937367
TI  - Minority language education in unbalanced bilingual situations: a case for the
      linguistic interdependence hypothesis.
AB  - This paper is placed in the linguistic and sociocultural context of Eastern
      Aragon, a region of Spain where two contact languages (Spanish and Catalan)
      coexist in an unbalanced situation favoring Spanish. The research was prompted by
      the regulation for the teaching of Catalan in that area, by means of the
      Cooperation Agreement signed by the Spanish Educational Ministry (MEC) and the
      local autonomous Cultural and Educational Department of the Diputacion General de
      Aragon in November 1986. A comparative analysis is made between Eastern Aragon
      students' linguistic competence in Catalan and Spanish; a further comparison is
      established between these students and others living in bilingual Catalonia and
      in monolingual Aragon. We conclude by pointing out that the Linguistic
      Interdependence Hypothesis accounts for the results obtained in the study.

PMID- 10937368
TI  - The WHO cross-national study on health behavior in school-aged children from 28
      countries: findings from the United States.

PMID- 10937369
TI  - Evaluation of HIV/AIDS education in Russia using a video approach.
AB  - HIV/AIDS has intruded upon the geographic, political, ethnic, gender, and sexual
      orientation of communities all over the world. As of April 1999, Russia has
      recorded approximately 13,532 cases of HIV infection. Since the costs of
      treatment are expensive for many countries, and especially for Russia,
      educational intervention appears to offer the most effective and affordable
      solution. A quasi-experimental design, with pre/post tests and intervention
      (through video education)/control groups, was used to study 20 public schools in
      St. Petersburg, Russia. Results confirmed the lack of HIV/AIDS education in
      schools and insufficient information sources from parents, friends, and public
      health education. ANCOVA statistics demonstrated that use of video education
      significantly improved students' scores on knowledge and attitudes related to
      HIV/AIDS prevention. Thus, health educators should consider video education as an
      effective and efficient tool to present facts to a young audience when they face
      constraints of shortage of funds, lack of trained teachers, and scarcity of
      related information.

PMID- 10937370
TI  - Relationship between cigarette, smokeless tobacco, and cigar use, and other
      health risk behaviors among U.S. high school students.
AB  - This study examined relationships between tobacco use and use of other
      substances, intentional injury risk behaviors, and sexual risk behaviors among US
      high school students. Data about tobacco use and other health risk behaviors were
      analyzed from the 1997 national Youth Risk Behavior Survey implemented by the
      Centers for Disease Control and Prevention. One-fourth of students (24%) reported
      current use of a single tobacco product (i.e., cigarettes, smokeless tobacco, or
      cigars during the 30 days preceding the survey), and 19.5% reported currently
      using more than one tobacco product. Generally, students who reported current
      tobacco use also reported engaging in other substance use, intentional injury
      risk behaviors, and sexual risk behaviors. For many risk behaviors, these results
      were especially pronounced among students who reported using two or all three
      tobacco products. Programs designed to prevent tobacco use should consider that
      such use often occurs concomitantly with other health risk behaviors.

PMID- 10937371
TI  - Health educators and child maltreatment: a curious silence.

PMID- 10937372
TI  - HealthTeacher.com: an online K-12 health education curriculum.

PMID- 10937373
TI  - Health promoting schools: why not in the United States?

PMID- 10937374
TI  - Intersectoral collaboration for the development of a national framework for
      health promoting schools in Australia.

PMID- 10937375
TI  - School-based health promotion across Australia.

PMID- 10937376
TI  - An audit of health promoting schools policy documentation.

PMID- 10937377
TI  - The nature of health service/school links in Australia.

PMID- 10937379
TI  - Impact of the national health promoting school initiative.

PMID- 10937378
TI  - Research into health promoting schools.

PMID- 10937380
TI  - Talking sexual health: a national application of the health promoting school
      framework for HIV/AIDS education in secondary schools.

PMID- 10937381
TI  - Occurrence of Salmonella typhi infection in Rourkela, Orissa.
AB  - Between January 1996 and December 1998, the isolation rate of Salmonella typhi in
      Rourkela was found to be on a steady rise. Of the 7866 samples (blood and bone
      marrow) tested, 988 were found positive for S. typhi giving an overall per cent
      positivity of 12.56. Enteric fever was found to occur almost throughout the year
      with a peak from early winter up to the end of summer. In this study,
      chloramphenicol was found to have an average sensitivity of 87.46 per cent.
      Ceftriaxone showed 100 per cent sensitivity.

PMID- 10937382
TI  - Characterization of methicillin resistant Staphylococcus aureus strains by a set
      of MRSA phages.
AB  - A recently developed international set of phages for typing methicillin resistant
      Staphylococcus aureus (MRSA) was used to characterize 300 strains of MRSA. The
      results were compared to that of phage typing with conventional phages and
      reverse phage typing. The use of MRSA phages increased the percentage typability
      from 17.6 per cent with the conventional set to 45.6 per cent with MRSA set and
      the strains were recognised as five distinct phage pattern viz., 622, M3/M5,
      MR8/MR12/MR25, 30/33/38 and mixed group. Phage type 622 was the most prevalent.
      On reverse phage typing 73 per cent strains could be typed with most strains
      belonging to one pattern i.e., 83A complex with limited discrimination. These 83A
      strains were highly resistant to erythromycin (98%) and tetracycline (93%). Our
      results show that MRSA phages are more useful in increasing typability and
      discrimination between the strains as compared to the conventional phages,
      reverse phage typing, and antibiogramtyping.

PMID- 10937383
TI  - Cost of mass annual single dose diethylcarbamazine distribution for the large
      scale control of lymphatic filariasis.
AB  - Economic analysis of the revised strategy to control lymphatic filariasis with
      mass annual single dose diethylcarbamazine (DEC) at 6 mg/kg body weight launched
      in one of the districts of Tamil Nadu in 1996 was carried out. This exploratory
      study, proposed for five years in 13 districts under 7 states on a pilot scale
      through the Department of Public Health is an additional input of the existing
      National Filaria Control Programme in India. A retrospective costing exercise was
      undertaken systematically from the provider's perspective following the
      completion of the first round of drug distribution. The major activities and cost
      components were identified and itemized cost menu was prepared to estimate the
      direct (financial) and indirect (opportunity) cost related to the implementation
      of the Programme. The total financial cost of this Programme to cover 22.7 lakh
      population in the district was Rs. 22.05 lakhs. The opportunity cost of labour
      and capital investment was calculated to be Rs. 7.98 lakhs. The total per capita
      cost was Rs. 1.32, with Rs. 0.97 and Rs. 0.35 as financial and opportunity cost
      respectively. Based on these estimates, the implementation cost of the Programme
      at Primary Health Centre (PHC) level was calculated and projected for five years.
      The additional financial cost for the existing health care system is estimated to
      be Rs. 27,800 per PHC every year. DEC tablets (50 mg) was the major cost
      component and sensitivity analysis showed that the cost of the Programme could be
      minimized by 20 per cent by switching over to 100 mg tablets. The analysis
      indicates that this Programme is a low-cost option and the results are discussed
      in view of its operational feasibility and epidemiological impact.

PMID- 10937384
TI  - Nutritional status of preschool children in the drought affected Kalahandi
      district of Orissa.
AB  - A community-based cross-sectional study was undertaken to determine the magnitude
      of undernutrition and protein-energy malnutrition among young children during
      1996-97 in drought affected Kalahandi district of Orissa. A total of 751 children
      aged 0-5 yr were studied for anthropometry and clinical signs of nutritional
      deficiencies from 15 Gram Panchayats selected using probability proportionate to
      size sampling. There was no significant difference between boys and girls for
      nutritional status. According to weight-for-age, 57.1 per cent of the children
      were suffering from underweight (< median -2SD) and 21.3 per cent of children had
      very low body weights which were < -3SD of standard. Height-for-age and weight
      for-height data showed that 41.8 per cent of children suffered from stunting and
      27.9 per cent recorded wasting. The children below one year of age had relatively
      lower prevalence of malnutrition than the other age groups. The prevalence of
      clinical PEM in the form of marasmus was found in 0.7 per cent of children, while
      kwashiorkor was absent. This study showed that malnutrition is still a leading
      problem among preschool children of Kalahandi district and this has not improved
      in spite of nutrition intervention programmes which are currently in operation.

PMID- 10937385
TI  - The development & characteristics of a physical activity questionnaire for
      epidemiological studies in urban middle class Indians.
AB  - A single page physical activity questionnaire was designed for use in
      epidemiological studies. The questionnaire estimates 24 h energy expenditure as
      well as components of occupation and discretionary leisure time activities.
      Estimates of physical activity were highly repeatable, when the questionnaire was
      re-administered within a 4 wk period (e.g., r = 0.86, P < 0.01 for 24 h energy
      expenditure). Relative validity was assessed by comparing energy intake (using
      repeated 24 h dietary recalls) and expenditure (using the physical activity
      questionnaire) over the same period. A correlate of r = 0.33, P < 0.05 between
      the two measures compared well with reports from literature. The discriminatory
      power of the questionnaire was assessed by comparing the physical activity
      patterns of young (18-30 yr) and older (> 60 yr), free living healthy subjects.
      The questionnaire provides a tool for the assessment of physical activity
      patterns of urban middle class Indians, which despite its importance has been
      inadequately studied so far.

PMID- 10937386
TI  - Role of IgM & IgA rheumatoid factors in complement activation in patients with
      juvenile rheumatoid arthritis.
AB  - We studied the relationship between the degree of complement activation in
      juvenile rheumatoid arthritis (JRA) with the levels of circulating IgM and IgA
      rheumatoid factors (RF). Forty children with JRA and 25 matched controls were
      included in the study. Levels of C3d (a degradation product of complement
      component C3), circulating immune complexes (CICs), IgM RF and IgA RF were
      measured by ELISA. Levels of C3d, CICs, IgM RF and IgA RF were elevated in
      patients with JRA as compared to controls. Levels of C3d had a linear
      relationship with levels of CICs (P < 0.05) but not with levels of circulating
      IgM RF and IgA RF. Thus, complement activation occurs in children with JRA and is
      associated with raised levels of CICs but not with levels of circulating IgM and
      IgA RF. Circulating IgM and IgA RF have little, if any, role in complement
      activation observed in patients with JRA.

PMID- 10937387
TI  - [Pilot study on personality disorders evaluation. Categorical DSM-IV vs.
      dimensional five factor models].
AB  - INTRODUCTION: This paper evaluates the relationship between a dimensional method
      of personality assessment (five factor model) and a categorical one (DSM-IV).
      METHODOLOGY: Thirty-eight consecutive outpatients without concurrent diagnosis of
      axis I, were assessed with the categorical instrument I.P.D.E. (International
      Personality Disorders Examination) and the dimensional one B.F.Q. (Big-Five
      Questionnaire). RESULTS: Extraversion differences were found among cluster and
      its components, Dominance and Dynamism. Extraversion, Dynamism, Cooperation and
      Persistence differences were found among personality disorders of cluster A.
      Personality disorders of cluster B were different in Mental Openness, Dynamism
      and Cooperation. Finally, Extraversion, Mental Openness, Dynamism, Cordiality,
      Openness to culture and Openness to experience differences were found among
      personality disorders of cluster C. CONCLUSIONS: This pilot study proposes the
      possibility of developing dimensional models to predict a possible personality
      disorder in future. Longitudinal studies with great samples are necessary to get
      this purpose, in where to be gathered a high percent from each personality
      disorder.

PMID- 10937388
TI  - [Spanish version of the new World Health Organization Disability Assessment
      Schedule II (WHO-DAS-II): initial phase of development and pilot study. Cantabria
      disability work group].
AB  - The aim of the present paper is to present the initial phases of the development
      of the Spanish version of the "World Health Organization Disablement Assessment
      Schedule II" WHO-DAS-II and also to describe the quantitative and qualitative
      methodological strategies used in the elaboration process of an instrument: i)
      compatible with the new International Classification of Functioning and
      Disability -ICIDH-2- of the World Health Organisation; ii) with criteria of cross
      cultural applicability and; iii) to allow us to assess the disability in all its
      dimensions.

PMID- 10937389
TI  - [The use of electroconvulsive therapy in acute services at the general hospital].
AB  - GOAL: The aim of the investigation focused on a retrospective analysis of the
      clinical use of ECT in the Acute Psychiatric Unit of The University Hospital of
      Guadalajara. METHOD: All patients admitted to our psychiatric unit from 1993 to
      1998 and who underwent ECT along their hospitalization, were included in the
      analysis. Age of the sample ranged from 17 to 79. Several variables were
      controlled, including technical parameters of ETC application. RESULTS: All
      patients with a diagnosis of bipolar disorder or schizoaffective disorder showed
      full remission after ECT. Among patients diagnosed of schizophrenia, 60%
      experimented full remission and 40% partial remission. In the group of subjects
      with depression, 66.6% showed full remission, 27.7% partial remission and 5.7% no
      response. Besides, ETC appeared to be more effective in subjects without
      psychiatric comorbidity. CONCLUSION: The present retrospective analysis support
      that ECT still must be considered an effective, useful and safe therapeutic
      technique. In our review, adverse reactions to ECT have been limited and rare,
      and mostly reversible.

PMID- 10937390
TI  - [Identification of the actual experiencing of pain. Methodological basis for an
      evaluation].
AB  - FUNDAMENTALS: The doctors don't have reliable instruments in order to detect the
      painful experience in a patient with intention of deceiving. The objective of
      this investigation is the development of an instrument that helps the doctors on
      that task. METHOD: The investigation is based on that the pain is not possible to
      evoke. A patient that doesn't feel pain, really, will introduce the modifications
      characteristic of all memory when requests you that he/she describe the pain that
      says feel. The will of deceit will also distort their description. A discriminant
      analysis will detect the difference between the description of a pain that is not
      present and another that yes it are, and between the sincere descriptions of the
      deceiving one. RESULTS: The descriptions of the pain carried out by two different
      samples of nursing students have been studied with a list of pair of antonym
      adjectives (Osgood's semantic differential). A subgroup of the first sample
      described a pain that they suffered in the same moment of description, and the
      other subgroup described a suffering pain some days before. In the other sample,
      a subgroup made a sincere description of their pain and other subgroup described
      the pain with will of deceiving the interviewer. The investigation has provided
      two discriminant models. A discriminant model differentiates between a present
      and another remembered pain (sensibility: 0.75; specificity: 0.85; kappa
      reliability: 0.60; p < 0.000000001; probability of success p: 89%). The other
      discriminant model differentiates between a description of a pain with will of
      deceiving and another pain described sincerely (sensibility: 0.94; specificity:
      0.95; kappa reliability: 0.89; p < 0.000000001; probability of success p: 97%).
      CONCLUSIONS: The results of this investigation seem to demonstrate that it is
      possible to discriminate between the descriptions of real pains and the
      suspicious pains of not being real, and that also one is able to discriminate
      between pains described with will of deceit and pains described sincerely. These
      discriminant models allows to classify the description of the subjects in four
      groups: "liars", "sincere", "magnifiers", and "psychogenic". However, it is
      necessary still carry out more effort of investigation so that these results
      could be replied in patients that suffer pain.

PMID- 10937391
TI  - [Effectiveness of group psychoanalytic therapy in somatizing patients].
AB  - Somatizers are a kind of patients very prevalent, expensive for the health system
      and difficult to treat. In recent years, several treatment approaches, such as
      cognitive, psychodynamic or educative therapy, have demonstrated effectiveness
      for the management of these patients. This paper aims to analyze the research
      studies on group psychotherapy for the treatment of somatizers. Most of these
      studies are not solid from a methodological point of view. Based on these data,
      the authors summarize the indications, methodology, limitations and effectiveness
      of group psychotherapy in the treatment of somatizing patients.

PMID- 10937392
TI  - [Neuropsychic injury: neuropsychological evaluation].
AB  - Traditionally assessment of cognitive function has not been employed adequately
      in our medical community. In the last two decades the neuropsychological
      assessment has experimented an evolution in order to improvement in specificity
      and sensitivity. In this paper we present a compendium of neuropsychological test
      that could be evaluate cognitive function adequately.

PMID- 10937393
TI  - [CAMDEX-R in the clinical evaluation of dementias].
AB  - CAMDEX has been very useful both for clinical use as epidemiological enquiries
      about dementia. However, the knowledge evolution about means that nowadays this
      schedule shows several shortcoming. A new version, CAMDEX-R, has adapted and
      introduced enough items to satisfy the actual requirements. The present article
      describes the changes and new contributions accomplished on the schedule.

PMID- 10937394
TI  - [Transcranial magnetic stimulation: contribution to psychiatry and to the study
      of brain-behavior relationship].
AB  - Transcranial Magnetic Stimulation (TMS) is a safe noninvasive technique to
      modulate cortical excitability. The introduction of repetitive TMS (rTMS)
      provides a new tool for studying psychopathologic disorders and higher cognitive
      functions. One of the most salient potential effects of rTMS is its possible
      therapeutic effect on different psychiatric disorders like depression, mania,
      obsessive compulsive disorder, post-traumatic stress disorder and schizophrenia.
      The mechanisms by which exerts its therapeutic effects are still unknown.
      However, the combination of this new methodology with functional neuroimaging
      techniques may help clarify what cerebral dysfunctions underly certain
      psychiatric conditions at the same time that it provides novel insights into
      brain cortico-cortical and cortico-subcortical connectivity.

PMID- 10937395
TI  - [Primary polydipsia and eating disorders: three case reports].
AB  - We present three patients with eating disorders and primary polydipsia with
      different severity and clinical relevance. This association is underestimated in
      common clinical practice, either due to hidden symptoms or lie over the real
      hydric intake, or due to lack of nosology location as a differentiated entity in
      nowadays nosologies, or by ignorance of the clinical features it can generate.
      These and other similar cases published in the literature indicate the real need
      to make a medical history focussed on hydric intake as part of the whole medical
      and psychiatric story and be alert if previous positive hyponatremia is recorder.
      Finally we propose five recommendations for the management and praecox diagnosis
      in order to avoid severe clinical consequences.

PMID- 10937396
TI  - Environmental health in environmental protection.
AB  - The health of the population and the environment are inextricably linked. To
      improve both, a holistic approach is required for environmental protection
      procedures. The primary approach for improvement is integration; more
      specifically an increase in communication between official departments and
      agencies, and mechanisms for stakeholder involvement from the inception of
      projects. There is also a need to combine HIAs and EIAs, and to apply them to
      wider issues, such as planning, policy or legislative changes, as well as
      traditional industrial development projects. It needs to be more widely
      appreciated that the economy and public health are ultimately substantially
      determined by the condition of the environment.

PMID- 10937397
TI  - Mortality variation across Australia: descriptive data for states and
      territories, and statistical divisions.
AB  - OBJECTIVE: To describe variation in all cause and selected cause-specific
      mortality rates across Australia. METHODS: Mortality and population data for 1997
      were obtained from the Australian Bureau of Statistics. All cause and selected
      cause-specific mortality rates were calculated and directly standardised to the
      1997 Australian population in 5-year age groups. Selected major causes of death
      included cancer, coronary artery disease, cerebrovascular disease, diabetes,
      accidents and suicide. Rates are reported by statistical division, and State and
      Territory. RESULTS: All cause age-standardised mortality was 6.98 per 1000 in
      1997 and this varied 2-fold from a low in the statistical division of Pilbara,
      Western Australia (5.78, 95% confidence interval 5.06-6.56), to a high in
      Northern Territory--excluding Darwin (11.30, 10.67-11.98). Similar mortality
      variation (all p < 0.0001) exists for cancer (1.01-2.23 per 1000) and coronary
      artery disease (0.99-2.23 per 1000), the two biggest killers. Larger variation
      (all p < 0.0001) exists for cerebrovascular disease (0.7-11.8 per 10,000),
      diabetes (0.7-6.9 per 10,000), accidents (1.7-7.2 per 10,000) and suicide (0.6
      3.8 per 10,000). Less marked variation was observed when analysed by State and
      Territory, but Northern Territory consistently has the highest age-standardised
      mortality rates. CONCLUSIONS: Analysed by statistical division, substantial
      mortality gradients exist across Australia, suggesting an inequitable
      distribution of the determinants of health. Further research is required to
      better understand this heterogeneity.

PMID- 10937398
TI  - Cost estimates for hospital inpatient care in Australia: evaluation of
      alternative sources.
AB  - OBJECTIVE: This paper presents a framework for evaluation of alternative sources
      of estimates of the costs of hospital inpatient care in Australia. It argues that
      the choice of costing methods depends on the decision-context and the sensitivity
      of the decision to estimation errors. METHOD: Five criteria are proposed for
      evaluation of sources of hospital cost data, with detailed consideration of the
      way estimates are derived in two computerised approaches which use accounting
      data. Three broad approaches to cost estimation are evaluated against these
      criteria. RESULTS: Choosing an estimation method entails an optimisation analysis
      for each decision context. 'Microcosting' techniques remains the most valid
      approach to cost estimation, but are costly and this may, in turn, limit the
      sample of patients or institutions. Protocol-based cost estimates vary widely in
      their validity, depending on source data, but there is little justification for
      continued use of crude per diem cost estimates in such protocols. When precision
      and resolution are important objectives, clinical costing approaches provide the
      most valid inpatient cost estimates at a reasonable data cost. When external
      validity is important, or where standardisation of hospital costs is desired, use
      of published national cost weights may be preferred. CONCLUSION: Both primary and
      secondary sources of cost data must withstand challenges to internal and external
      validity. The 'resolution' (or precision) of cost estimates and the relative
      costs of collection must also be considered. IMPLICATIONS: Studies using
      estimates of the costs of hospital care should defend the appropriateness of the
      costing approach and data source for the decision context.

PMID- 10937399
TI  - A randomised trial of an intervention to develop health promoting schools in
      Australia: the south western Sydney study.
AB  - OBJECTIVE: This paper describes the evaluation of a health promoting schools
      intervention carried out in the south western region of Sydney, Australia. The
      evaluation sought to assess the project's impact on structures to support the
      health promoting school concept and changes in health-related policies and
      practices within 22 local schools. METHODS: A randomised controlled study was
      employed. Intervention schools were offered seminars and training in the health
      promoting schools concept, encouraged to use a resource kit to help them
      establish their school as health promoting and invited to participate in a
      support network. Pre- and post measures of awareness, school structures and
      policies and practices to support the development of a health promoting school
      were taken and intervention and control schools compared. RESULTS: There was an
      increased level of awareness of the health promoting school concept among
      intervention schools. However, there were no significant changes in health
      related policies and practices at the school level, among both intervention and
      control schools. CONCLUSIONS: A longer time frame and more structured support are
      required to influence school structures to support the development of a health
      promoting school. IMPLICATIONS: To facilitate organisational change in schools,
      health promoting school interventions need to provide structured support for
      schools and recognise that change takes time. A committee to initiate action, a
      plan to guide work and school support are likely to facilitate the adoption of
      the health promoting schools approach. Further work to refine the measurement of
      school-based action and its outcome and the development of indicators for a
      health promoting school is needed.

PMID- 10937400
TI  - Cost effectiveness analysis of school based Mantoux screening for TB infection.
AB  - OBJECTIVE: To assess the cost-effectiveness of adding school based Mantoux
      screening programs to the New South Wales current TB prevention strategy. METHOD:
      A decision analysis model compared the costs and consequences of screening
      strategies against the current no-screen strategy. Costs associated with
      screening and with treating future cases of TB were considered. Consequences
      considered were deaths and adult cases of TB prevented. The study was based on
      data from prevalence surveys conducted in 1992 and 1994 in Central and South
      Western Sydney, New South Wales. Screening strategies considered were screening
      all or only overseas born (OSB) 6 year olds and all or only OSB 14 year olds in
      school settings. RESULTS: Screening 14 year olds prevented more deaths and adult
      cases of TB than screening 6 year olds for a similar cost. For both age groups
      targeted screening of OSB children was more cost-effective than screening all
      children. Targeted screening of 14 year olds--the most cost effective option-
      cost $17,956 (costs and benefits discounted at 5%) per adult case prevented,
      equivalent to approximately $130,000 per life year saved. The cost-effectiveness
      ratios decline substantially if lower discount rates and less conservative
      assumptions are applied. CONCLUSION: Targeted screening was more cost effective
      than screening all children, however, there are ethical implications of targeting
      a group based on their origin of birth. IMPLICATIONS: As prevention and control
      of TB continues to be a high priority for NSW, the implications of a school based
      screening program should be seriously considered.

PMID- 10937401
TI  - 'Sending the wrong signal': analysis of print media reportage of the ACT heroin
      prescription trial proposal, August 1997.
AB  - OBJECTIVE: To analyse and compare newspaper coverage about heroin during a period
      spanning two government policy decisions to approve, then prevent, a trial of
      heroin prescription to dependent users. METHOD: All articles published about
      heroin spanning the two policy decisions (1-19 August 1997) were collected from
      seven major Australian newspapers. Analyses included content and orientation
      analyses of all articles and discourse analysis of articles (excluding letters)
      containing value-laden statements about heroin prescription. Comparisons were
      made of content, orientation and subtextual themes employed by opponents and
      proponents of heroin prescription. RESULTS: 231 articles with references to
      heroin were identified from seven newspapers, 28% were published by The Daily
      Telegraph. This newspaper campaigned against the heroin prescription trial with
      66% of news articles and 100% of opinion items negative in orientation, compared
      to averages of 11% and 16% of news and opinion articles published by comparison
      newspapers. Seven subtexts were identified in coverage opposing heroin
      prescription including "surrender in the war on drugs", "government as drug
      pedlar" and "deserving/undeserving citizens". Six subtexts supportive of heroin
      prescription were identified including "failure of prohibition" and "time for new
      approaches". CONCLUSION: The mid-1997 policy reversal on heroin prescription was
      due, in part, to the higher activity of opponents following approval of the trial
      and because proponents did not reframe discourses used to denigrate the proposal.
      IMPLICATIONS: To be successful, advocates of new policy need to recognise and
      reframe negative discourses to create new dominant themes which address the
      concerns of the public.

PMID- 10937402
TI  - The cost effectiveness of a home hazard reduction program to reduce falls among
      older persons.
AB  - BACKGROUND: The effectiveness of individual components (other than exercise) of
      multifactorial intervention packages aimed to reduce the incidence of falls in
      older people is uncertain. There have been no randomised trials of home
      modifications alone for the prevention of falls. OBJECTIVES: To estimate the cost
      effectiveness of just one component of a multifactorial approach to falls
      prevention, that is, a home hazard reduction program. The study estimates the
      size and direction of change in resource use within and between the hospital,
      home and community sectors. METHODS: A randomised trial was conducted to evaluate
      the effectiveness of home modifications for prevention of falls among older
      people. An occupational therapist (O/T) with experience in aged care assessed
      homes for environmental hazards and supervised the necessary home modifications.
      SUBJECTS: The subjects in this study were people aged 65 years and older and most
      were recruited during a hospital stay. The cost-effectiveness analysis was based
      on a randomised trial with a total of 530 subjects. RESULTS: The incremental cost
      per fall prevented was $4,986. A sensitivity analysis was conducted by removing
      12 outlier subjects (6 control and 6 intervention). The incremental cost per fall
      prevented was $1,921 for all subjects and was cost saving for subjects who had
      fallen in the 12 months prior to randomisation. CONCLUSIONS & IMPLICATIONS: A
      single factor home hazard reduction program is more likely to be most cost
      effective amongst older people who have a history of falls.

PMID- 10937404
TI  - An unbridgeable gap? Comparing the HIV/AIDS epidemics in Australia and sub
      Saharan Africa.
AB  - OBJECTIVE: To compare the HIV/AIDS epidemics in Australia and sub-Saharan Africa,
      to outline reasons for differences, and to consider implications for the Asia and
      Pacific region. METHODS: Comparison of key indicators of the epidemic in
      Australia, and Africa viewed largely through the experience of the Hlabisa health
      district, South Africa. RESULTS: To the end of 1997, for all Australia, the
      estimated cumulative number of HIV infections was approximately 19,000, whereas
      in Hlabisa 31,000 infections are estimated to have occurred. Compared with the
      low and declining incidence of HIV in Australia (< 1%), estimated incidence in
      Hlabisa rose to 10% in 1997. In all, 94% of Australian infections have been
      amongst men; in Hlabisa equal numbers of males and females are infected.
      Consequently, whereas 3000 children were perinatally exposed to HIV in Hlabisa in
      1998 alone, 160 Australian children have been exposed this way. In Australia, HIV
      related disease is characterised by opportunistic infection whereas in Hlabisa
      tuberculosis and wasting dominate. Surveys among gay men in Sydney and Melbourne
      indicate > 80% of HIV infected people receive antiretroviral therapy whereas in
      Hlabisa these drugs are not available. IMPLICATIONS: It seems possible that Asia
      and the Pacific will experience a similar HIV/AIDS epidemic to that in Africa.
      Levels of HIV are already high in parts of Asia, and social conditions in parts
      of the region might be considered ripe for the spread of HIV. As Australia
      strengthens economic and political ties within the region, so should more be done
      to help Pacific and Asian neighbours to prevent and respond to the HIV epidemic.

PMID- 10937403
TI  - An outbreak of cryptosporidiosis in an urban swimming pool: why are such
      outbreaks difficult to detect?
AB  - OBJECTIVE: To describe an outbreak of Cryptosporidium gastroenteritis in a
      swimming pool in Melbourne in early 1998 that was not detected through routine
      surveillance, and discuss difficulties in identifying such outbreaks. METHODS:
      The Water Quality Study (WQS) was a large community-based study of
      gastroenteritis. Following suspicion of an outbreak of cryptosporidiosis within
      the study group, due to pool "X", a nested case control study was performed. Each
      case of Cryptosporidium gastroenteritis was matched with six controls and data
      from weekly Health Diaries from the WQS were reviewed. The Department of Human
      Services also instigated active surveillance among patrons at pool "X" using a
      systematic sample of 50 people from the pool's swim-school enrollment list.
      RESULTS: There were seven cases of Cryptosporidium gastroenteritis in the case
      control study. Five cases and eight controls swam at pool "X" during the outbreak
      period. The adjusted odds of developing cryptosporidial diarrhoea if an
      individual swam at pool "X" was 34.5 (CI 2.3-2548). DHS identified another 11
      laboratory confirmed cases associated with pool "X" as well as cases not linked
      to pool "X". 125 cases were identified throughout Melbourne with the suspected
      involvement of seven swimming pools. CONCLUSIONS: Despite a high odds ratio of
      developing cryptosporidiosis this outbreak was not detected by routine
      surveillance methods. Current outbreak detection methods lack sensitivity,
      specificity or timeliness. IMPLICATIONS: Improved surveillance systems are
      required if outbreaks of gastroenteritis are to be detected early so an
      intervention can be instigated to reduce the amount of subsequent illness.

PMID- 10937405
TI  - Differential effects on socioeconomic groups of modelling the location of
      mammography screening clinics using Geographic Information Systems.
AB  - OBJECTIVE: To evaluate spatial access to mammography clinics and to investigate
      whether relocating clinics can improve global access. To determine whether any
      change in access is distributed equitably between different social groups.
      METHODS: The study was undertaken in Perth, Western Australia in 1996. It was an
      analysis of travel distances to mammography clinics, comparing distances to the
      pattern of existing clinics and modelled relocated clinics. The study population
      was the 151,162 women aged 40-64 years resident in Perth in 1991. RESULTS:
      Overall travel distances to the existing clinics was reduced by 14% when a GIS
      system was used to relocate them so as to minimise the travel distance for all
      women. The travel distance of the most disadvantaged groups fell by 2% and by 24%
      for the least disadvantaged group. CONCLUSIONS: GIS modelling can be used to
      advantage to evaluate potential locations for screening clinics that improve the
      access for the target population, however global analysis should be supplemented
      by analysis of special groups to ensure that no group is disadvantaged by the
      proposal. IMPLICATIONS: If new technology is not used to evaluate the placement
      of health services, population travel distances may be greater than necessary,
      with possible impacts on attendance rates.

PMID- 10937406
TI  - Size for gestation in Aboriginal babies: a comparison of two papers.
AB  - OBJECTIVE: Two recent papers examining low birthweight in Aboriginal infants came
      to different conclusions about the role of size for gestation and preterm
      delivery in influencing the low birthweight proportion. As the two studies used
      different methods to estimate the infants' gestational age and to analyse the
      data, the results cannot be compared directly. This analysis combines the methods
      of both earlier studies. METHOD: Data collected in 6 Top End communities were
      analysed to calculate the proportion of infants who were small for gestational
      age. RESULTS: Despite the high overall prevalence of preterm delivery from the
      midwives' estimates, 31.4% of infants fell below the 10th centile of weight for
      gestational age and sex. The majority of these infants were not low birthweight.
      CONCLUSIONS: The earlier report from the Top End of high proportions of small-for
      gestational age infants cannot be dismissed as an artefact due to the method of
      estimating gestational age. IMPLICATIONS: Intervention programs to improve birth
      weights in Aboriginal infants need to address both conditions--small size for
      gestational age and preterm delivery--and need to target the whole population
      rather than high risk pregnancies.

PMID- 10937407
TI  - The urban and rural divide for women giving birth in NSW, 1990-1997.
AB  - OBJECTIVE: To examine trends in the pregnancy profile and outcomes of urban and
      rural women. METHODS: Data were obtained from the NSW Midwives Data Collection on
      births in NSW, 1990-1997. Associations between place of residence (urban/rural)
      and maternal factors and pregnancy outcomes were examined, including changes over
      time. RESULTS: From 1990 to 1997 there were 685,631 confinements in NSW and these
      mothers resided as follows: 76% metropolitan, 5% large rural centres, 8% small
      rural centres, 11% other rural areas and 1% remote areas. Rural mothers were more
      likely to be teenagers, multiparous, without a married or de facto partner,
      public patients and smokers. Births in rural areas declined, particularly among
      women aged 20-34 years. Infants born to mothers in remote communities were at
      increased odds of stillbirth and low Apgar scores (all women) and small-for
      gestational- age (SGA) (Indigenous women only). CONCLUSIONS: The profile of
      pregnant women in rural NSW is different from their urban counterparts and is
      consistent with relative socioeconomic disadvantage and possibly suboptimal
      maternity services in some areas. While increased risk of SGA is associated with
      environmental factors such as smoking and nutrition, the reasons the increased
      risk of stillbirth are unclear. Although there does not appear to be an increase
      d risk of preterm birth for rural women this may be masked by transfer of high
      risk pregnancies interstate. IMPLICATIONS: Maternity services need to be
      available and accessible to all rural women with targeting of interventions known
      to reduce low birthweight and perinatal death.

PMID- 10937408
TI  - Randomised controlled trial of an educational strategy to increase school-based
      adolescent hepatitis B vaccination.
AB  - OBJECTIVES: This study aimed to evaluate a specifically designed hepatitis B
      education/promotion curriculum package as part of a successful hepatitis B
      vaccination delivery system to adolescents. METHODS: A randomised-controlled
      trial was used to evaluate the effect of the curriculum package (or intervention)
      on uptake of vaccine. Schools were randomly selected from the metropolitan region
      of Melbourne to intervention (66 schools or 7,588 students) or control groups (69
      schools or 9,823 students). Class teachers administered the intervention to
      students over 4 class periods before the vaccination course. RESULTS: The
      difference in mean school uptake between intervention and control was small at 1
      2% per dose. 95% confidence intervals around the differences were -5% to 2% per
      dose and not significant. Intervention schools taught an average of 7 items out
      of 12 from the curriculum package. Immunisation rates increased by 4-10% per dose
      between low and high implementation schools, but this trend was not significant.
      Impact evaluation demonstrated significantly greater knowledge of hepatitis B and
      vaccination among students in the intervention than the control group.
      CONCLUSION: Hepatitis B vaccination of pre-adolescents was not increased by the
      implementation of a curriculum package that successfully increased knowledge and
      awareness of hepatitis B in a school-based vaccination program. Additional
      strategies directed at the education of parents, the cooperative role of schools
      and pro-active providers might also be required to maximise vaccine uptake in
      this age group.

PMID- 10937409
TI  - A randomised controlled trial of the costs of hospital as compared with hospital
      in the home for acute medical patients.
AB  - OBJECTIVE: To test the cost effectiveness of Hospital in the Home compared to
      hospital admission for acute medical conditions. METHOD: Randomised controlled
      trial at the Prince of Wales Hospital, Sydney, from October 1995 to February,
      1997; 100 patients with acute medical conditions admitted through the Emergency
      Department. RESULTS: The Hospital in the Home (HITH) group costs per separation
      ($1,764, CI 95% $1,416-$2,111, n = 50) were significantly lower (p < 0.0001, Mann
      Whitney U-Wilcoxon Rank Sum) than the control group hospital separation ($3,614,
      CI 95% $2,881.37-$4,347.27, n = 47) with no significant difference in clinical
      outcomes, and comparable or better user satisfaction. CONCLUSION: Given the
      favourable clinical outcomes the HITH model produces at a lower cost, the cost
      effectiveness of the care mode is high, and the allocative efficiency favourable.
      IMPLICATIONS: As a care model and critical pathway, HITH offers hospitals real
      bed day savings that can either be used to rationalise resource usage for a given
      level of activity, or increase throughput.

PMID- 10937410
TI  - Dissemination of responsible service of alcohol initiatives to rugby league
      clubs.
AB  - OBJECTIVES: To determine the acceptability of intervention strategies that
      increase the responsible service of alcohol by non-metropolitan rugby league
      clubs. METHOD: Rugby league clubs were provided an information kit and advice by
      local public health workers, police and a lead agency regarding their responsible
      service of alcohol practices. Rugby League clubs and public health workers
      completed an acceptability survey at the conclusion of the study. RESULTS: Data
      were collected from 160 contactable clubs (100% consent) and 12 of 14
      participating public health workers. Almost all clubs reported of contact with
      the lead agency, public health workers and police to be acceptable. Fifty-nine
      percent of clubs reported contact with public health workers to be useful. One
      third of the public health workers considered that they were not the most
      suitable professional group to be involved in delivering the intervention.
      CONCLUSIONS: In spite of a suggested culture of harmful alcohol consumption among
      rugby league participants and spectators, non-metropolitan rugby league clubs
      appear receptive to public health strategies that increase their responsible
      service of alcohol. IMPLICATIONS: The ability of the public health sector to meet
      this opportunity appears limited, and may require additional strategies to
      increase the capacity of public health workers to develop/deliver inter-sectorial
      interventions in this setting.

PMID- 10937411
TI  - Trends in birth rates for teenagers in Queensland, 1988 to 1997: an analysis by
      economic disadvantage and geographic remoteness.
AB  - OBJECTIVE: To investigate trends in the birth rate for teenagers in Queensland,
      stratified by geographic remoteness and economic disadvantage. METHOD: This was
      an analysis of routine data for the period 1988 to 1997. The number of births
      were obtained from the Queensland Perinatal Data Collection. Population data (the
      denominators for the rates) were obtained from the Australian Bureau of
      Statistics. Economic disadvantage was based on place of usual residence of the
      mother. Because of differences in physical, social and psychological development,
      the data were analysed in three age groups: 13 to 14 years, 15 to 17 years and 18
      to 19 years. RESULTS: Birth rates to teenagers who live in disadvantaged areas
      were 2 to 4 times higher than the rates for all of Queensland and 10 to 20 times
      higher than the rates in affluent areas. The trend analysis showed that the rates
      are decreasing in urban-affluent areas (about 2.5% per year), while they have
      remained stable, but extremely high in disadvantaged-remote areas, and are
      increasing (about 5% per year) in disadvantaged-urban areas. CONCLUSIONS: The
      relatively low and stable rates for all of Queensland have hidden marked
      variations in the trends for areas defined according to economic disadvantage and
      remoteness. The rates were especially high and showed no improvement over time in
      remote disadvantaged areas, which have a large indigenous population.
      IMPLICATIONS: In some areas of Queensland births to teenagers is a pressing
      problem, especially because it can perpetuate a cycle of limited educational
      opportunities, social isolation and reliance on welfare.

PMID- 10937412
TI  - Prevalence and acceptability of public health initiatives in licensed premises.
AB  - OBJECTIVES: To determine the prevalence and acceptability of public health
      initiatives in licensed premises. METHODS: Licensees/managers of all 333 licensed
      premises in the Hunter Region of NSW were interviewed to assess the practice of,
      and interest in undertaking public health initiatives relating to: responsible
      service of alcohol; environmental tobacco smoke; healthy-food choices; skin,
      breast and cervical cancer prevention; and the prevention of HIV/AIDS. RESULTS:
      Ninety eight percent of contacted premises participated in the study.
      Approximately two-thirds of premises reported having a responsible service of
      alcohol policy and training their staff in responsible service. One third of
      premises reported the provision of healthy food choices and smoke-free areas.
      Initiatives concerned with the prevention of cancer and HIV/AIDS were practised
      by less than 25% of premises. Between 41% and 85% of premises expressed an
      interest in undertaking all but two initiatives. Almost all interested premises
      accepted the offer of resources to facilitate adoption of public health
      initiatives. CONCLUSIONS: The study suggests that licensed premises are already
      involved in a number of public health initiatives, and that they appear willing
      to consider the introduction of a wide range of such initiatives. IMPLICATIONS:
      The prevalence of public health initiatives in licensed premises, and the extent
      of interest expressed by licensees/managers in undertaking such initiatives
      suggests that both a need and an opportunity exist for public health and other
      agencies to be more actively involved in disseminating appropriate services in
      this setting.

PMID- 10937413
TI  - Alcohol consumption in a community sample of older people.
AB  - OBJECTIVE: To examine the prevalence and pattern of alcohol use among community
      living elderly Australians. METHODS: A survey was conducted of randomly selected
      non-institutionalised people aged 75 years and older living in the inner western
      suburbs of Sydney. Personal interviews by trained interviewers covered background
      demographic information and self-reported alcohol use. RESULTS: 72% of men and
      54% of women drank alcohol. The median usual daily volume of ethanol consumed by
      drinkers was 10 grams for men and 1.3 grams for women. However 11% of male
      drinkers and 6% of female drinkers consumed at defined hazardous or harmful
      levels. CONCLUSIONS AND IMPLICATIONS: Although a sizeable majority of these older
      people were either non-drinkers or very light drinkers, a small but important
      proportion drank in the hazardous to harmful range. Despite increasing evidence
      of the health benefits of alcohol consumption it remains important to be alert
      for potentially harmful alcohol use among older people.

PMID- 10937414
TI  - An analysis of resources for indigenous women in NSW about cervical screening.
AB  - OBJECTIVE: To examine resources about cervical screening made available to
      Indigenous women in NSW. METHOD: An Aboriginal woman, on behalf of another
      Aboriginal woman, telephoned 47 NSW based organisations in May 1998 for
      information about cervical screening. Received materials were analysed for
      format, content and readability and then submitted to a panel of Indigenous women
      for their feedback. RESULTS: Of those 34 organisations agreeing to send
      resources, only 20 (59%) did so. After removing duplicates, 12 cervical screening
      resources were available for review of which six were designed and printed in NSW
      and the other six originated outside NSW. Of the six resources developed in NSW,
      two (33%) were for Aboriginal women. Of the six resources originating from
      outside of NSW, another two (33%) also were for Aboriginal women. The Flesch
      readability scores for resources ranged from 58.6 to 87.27. Those developed in
      NSW had a significantly lower readability score than those from outside of NSW (p
      = 0.025). Despite lower education levels among the target group, there was no
      difference in the readability scores of resources designed for Indigenous women
      (p = 1). CONCLUSIONS: Most resources obtained by us were not tailored for
      Indigenous women. IMPLICATIONS: This study has set a base line for resources
      available for Indigenous women. Our method could be replicated in the future to
      evaluate and monitor improvement.

PMID- 10937415
TI  - Too fat to exercise? Obesity as a barrier to physical activity.
AB  - OBJECTIVE: To describe perceptions of being 'too fat' as a barrier to physical
      activity by gender and body mass index, and to examine the associations between
      feeling fat and other weight-related barriers to physical activity. METHODS:
      Analyses of cross-sectional self-report data from a representative population
      survey of 2,298 Australian adults. RESULTS: Overall, 4.4% of respondents reported
      being too fat as a barrier to physical activity; this being more common among
      women (6.2%), and among the obese (22.6%). Associations were found between being
      too fat as a barrier, and being too shy or embarrassed to exercise; being too
      lazy or not motivated; having an injury or disability (males only); and being not
      the sporty type (females only). There was no association between feeling too fat
      and poor health. CONCLUSIONS: Feeling too fat to exercise is a common barrier
      among the overweight, particularly for women. Results suggest gender differences
      in weight-related barriers to physical activity. IMPLICATIONS: A better
      understanding of the nature of weight-related physical activity barriers can help
      inform public health strategies designed to increase physical activity among
      those who are obese.

PMID- 10937416
TI  - Tracking participants: lessons from the Women's Health Australia Project.

PMID- 10937417
TI  - Public health should not be a popularity contest: a reply to Gavin Mooney.

PMID- 10937418
TI  - Community autonomy remains crucial to public health, despite measurement
      difficulties: a response to Simon Chapman.

PMID- 10937419
TI  - Social capital should not be incorporated into surveys designed to monitor
      population health.

PMID- 10937420
TI  - Public health surveys and the measurement of social capital. Response to letter
      titled "Social capital should not be incorporated into surveys designed to
      monitor population health".

PMID- 10937421
TI  - Norwalk-like virus as a cause of a gastroenteritis outbreak in a childcare
      centre.

PMID- 10937422
TI  - Birth weight as a health outcome measure.

PMID- 10937423
TI  - Evidence for a large consumption of blackmarket processed-leaf-tobacco throughout
      the eastern states of Australia.

PMID- 10937424
TI  - Disgust sensitivity and contamination fears in spider and blood-injection-injury
      phobias.
AB  - Disgust has been implicated in the onset and maintenance of blood-injection
      injury (BII) and animal phobias. Research suggests that people with these phobias
      are characterized by an elevated sensitivity to disgust-evoking stimuli separate
      from their phobic concerns. The disgust response has been described as the
      rejection of potential contaminants. Disgust-motivated avoidance of phobic
      stimuli may therefore be related to fears of contamination or infection. The
      present study compared BII phobics, spider phobics and nonphobics on two measures
      of disgust sensitivity and two measures of contamination fears. Positive
      correlations were found between disgust sensitivity and contamination fear.
      Specific phobics scored higher than nonphobics on all scales and BII phobics
      scored higher than spider phobics on contamination fear measures. Furthermore,
      the contamination fear scales were correlated with the blood phobia measure, but
      not correlated with the spider phobia measure. The results suggest that while
      both phobias are characterized by elevated disgust sensitivity, contamination
      fear is more prominent in BII than spider phobia.

PMID- 10937425
TI  - If you suffer from a headache, then you have a brain tumour: domain-specific
      reasoning 'bias' and hypochondriasis.
AB  - We explored whether hypochondriacal patients selectively search for threat
      confirming information when asked to judge the validity of conditional rules in
      the context of general and health threats. We also explored several factors that
      may underly participants' information selection (e.g., believability of the
      rule). Hypochondriacal patients (n = 20) and healthy controls (n = 20) were
      presented with modified Wason Selection Tasks (WSTs). The WSTs contained safety
      rules and danger rules. In the context of general threat, both groups of
      participants adopted a verificationistic strategy in the case of danger rules and
      a Popperian strategy in the case of safety rules. Importantly, only
      hypochondriacal persons showed a similar threat-confirming reasoning pattern in
      the context of health threat. The latter finding contrasts with the earlier study
      of de Jong et al. (1998) [de Jong, P. J., Haenen, M.-A., Schmidt, A., & Mayer, B.
      (1998a). Hypochondriasis: the role of fear-confirming reasoning. Behaviour
      Research and Therapy, 36, 65-74; de Jong, P. J., Mayer, B., van der Hijden, B.,
      Bogels, S., & van den Hout, M. (1998b). Better safe than sorry: reasoning with
      conditionals in the context of threat. Submitted for publication.] in which both
      hypochondriacs and healthy controls showed a threat-confirming strategy in the
      domain of health threat. The WSTs in that study however, contained a (unintended)
      worry manipulation ("after hearing this, you get worried"), which might have
      induced a reasoning strategy in controls that is normally restricted to
      hypochondriacs. Taken together, the present results sustain the idea that the
      perception of threat activates a better safe than sorry strategy. In the case of
      phobic threats, such a reasoning strategy immunizes against refutation of phobic
      convictions.

PMID- 10937426
TI  - Applied relaxation vs. cognitive therapy in the treatment of generalized anxiety
      disorder.
AB  - The present study investigated the efficacy of a coping-technique, applied
      relaxation (AR) and cognitive therapy (CT), in the treatment of generalized
      anxiety disorder. Thirty-six outpatients fulfilling the DSM-III-R criteria for
      generalized anxiety were assessed with independent assessor ratings and self
      report scales before and after treatment and at a 1 yr follow-up. The patients
      were randomized and treated individually for 12 weekly sessions. The results
      showed that both treatments yielded large improvements, which were maintained, or
      furthered at follow-up. There was no difference between AR and CT on any measure.
      The drop-out rate was 12% for AR and 5% for CT. The proportions of clinically
      significantly improved patients were 53 and 62% at post-treatment and 67 and 56%
      at follow-up for AR and CT, respectively. Besides affecting generalized anxiety
      the treatments also yielded marked and lasting changes on ratings of worry,
      cognitive and somatic anxiety and depression. The conclusion that can be drawn is
      that both AR and CT have potential as treatments for generalized anxiety disorder
      but they have to be developed further in order to increase the efficacy to the
      level usually seen in panic disorder, 80-85% clinically improved.

PMID- 10937427
TI  - Psychological confounds in medical research: the example of excessive cough in
      asthma.
AB  - This experiment tested the hypothesis that the setting in which research is
      conducted may dominate symptom magnitude. Cough was induced with inhaled citric
      acid and its magnitude was influenced by changing the setting in 30 adolescents
      with asthma. Cough thresholds for citric acid were determined. The participants
      were assigned to a condition emphasising asthma, or a control condition,
      described as estimation of lemon flavors. All participants inhaled (in different
      order) thresholds for citric acid, 50% of these thresholds, or placebo. Results
      showed that both cough frequency and subjective 'cough tendency' were
      significantly higher in the asthma condition. State anxiety was higher in the
      asthma condition, but correlated only moderately with cough. Lung function,
      severity of asthma, trait anxiety, age or sex did not correlate with cough. It
      was concluded that patients with asthma cough more often in a situation which
      they have learned to associate with asthma.

PMID- 10937429
TI  - How serious are common childhood fears? II. The parent's point of view.
AB  - In an earlier study [Muris, P., Merckelbach, H., Mayer, B., & Prins, E. (1999).
      How serious are common childhood fears? Behaviour Research and Therapy, in
      press.], the severity of common childhood fears was explored by means of a
      structured child interview measuring specific phobias as defined by the
      Diagnostic and Statistical Manual of Mental Disorders. It was found that in a
      substantial minority of the children, specific fears reflect clinically
      significant phobias. The present study examined further the connection between
      childhood fears and specific phobias by interviewing children's parents. The
      Diagnostic Interview Schedule for Children was administered to the parents of 160
      children aged 4-12 years. In line with our previous study, results indicate that
      a sizable proportion of children (i.e. 17.6%) met the full criteria for specific
      phobia.

PMID- 10937428
TI  - Evidence of a disposition toward fearfulness and vulnerability to posttraumatic
      stress in dysfunctional pain patients.
AB  - Few investigations have addressed whether patient subgroups derived using the
      Multiaxial Assessment of Pain (MAP) [Turk, D. C., & Rudy, T. E. (1987). Towards a
      comprehensive assessment of chronic pain patients. Behaviour Research and
      Therapy, 25, 237-249; Turk, D. C., & Rudy, T. E. (1988). Toward an empirically
      derived taxonomy of chronic pain patients: integration of psychological
      assessment data. Journal of Consulting and Clinical Psychology, 56, 233-238.]
      differ with regard to fear and avoidance. It has, however, been reported that
      dysfunctional patients exhibit more pain-specific fear and avoidance than
      patients classified as interpersonally distressed or minimizers/adaptive copers
      [Asmundson, G. J. G., Norton, G. R., & Allerdings, M. D. (1997). Fear and
      avoidance in dysfunctional chronic back pain patients. Pain, 69, 231-236.]. We
      attempted to extend these findings by examining two fear constructs that are
      receiving increased attention in the chronic pain literature-anxiety sensitivity
      and PTSD. The sample comprised 115 patients with chronic pain. Of these, 14
      (12.2%) were classified as dysfunctional, 21 (18.3%) as interpersonally
      distressed and 47 (40.8%) as minimizers/adaptive copers. Between-group
      differences were observed on the fear of cognitive and emotional dyscontrol
      dimension of anxiety sensitivity, total and symptom cluster scores on the PTSD
      measure, and depression. No differences were observed for the fear of somatic
      sensations dimension of anxiety sensitivity or agoraphobia, social phobia, and
      blood/injury fears. Dysfunctional patients generally exhibited elevated scores
      relative to one or both of the other MAP subgroups on fear of cognitive and
      emotional dyscontrol, depressed affect, PTSD symptom total score and PTSD symptom
      cluster scores. As well, a substantial proportion of dysfunctional and
      interpersonally distressed patients were classified as having PTSD (71.4 and
      42.9%, respectively) when compared to minimizers/adaptive copers (21.3%). These
      results suggest that MAP subgroups differ with regard to their propensity to
      be(come) fearful and in their likelihood of having PTSD. Theoretical and clinical
      implications are discussed.

PMID- 10937430
TI  - Hypochondriacs' estimation of negative outcomes: domain-specificity and
      responsiveness to reassuring and alarming information.
AB  - Based on hypochondriacal patients' tendency to overestimate the seriousness of
      bodily sensations and health risks [Barsky, A. J., Wyshak, G. & Klerman, G. L.
      (1990). The Somatosensory Amplification Scale and its relationship to
      hypochondriasis. Journal of Psychiatric Research, 24, 323-334; Warwick, H. M. C.,
      & Salkovskis, P. M. (1990). Hypochondriasis. Behaviour Research and Therapy, 28,
      105-117], we investigated whether hypochondriacal individuals (n = 20) are
      inclined to report higher estimates of negative outcomes than healthy controls (n
      = 20) when interpreting ambiguous health-related and nonhealth-related events. In
      addition, we explored the influence of additional reassuring and alarming
      information on hypochondriacs' estimates of negative outcomes. Following the
      cognitive-behavioural model of hypochondriasis [Warwick, H. M. C. & Salkovskis,
      P. M. (1989). Hypochondriasis. In J. Scott, J. M. G. Williams & A. T. Beck
      (Eds.), Cognitive therapy in clinical practice: an illustrative casebook. (pp. 78
      102). London: Routledge] we hypothesized that hypochondriacal individuals would
      be more responsive to alarming information and less responsive to reassuring
      information than healthy controls. Yet, hypochondriacs were neither found to be
      immune for reassuring information, nor to be hypersensitive to alarming
      information. Meanwhile, irrespective of the additional alarming or reassuring
      information, hypochondriacs clearly showed a domain-specific bias towards higher
      estimates of negative outcomes in ambiguous health-related situations.

PMID- 10937431
TI  - Assessment of symptoms of DSM-IV anxiety and depression in children: a revised
      child anxiety and depression scale.
AB  - The practical significance of assessing disorders of emotion in children is well
      documented, yet few scales exist that possess conceptual if not empirical
      relevance to dimensions of DSM anxiety or depressive disorders. The current study
      evaluated an adaptation of a recently developed anxiety measure (Spence
      Children's Anxiety Scale; [Spence, S. H. (1997). Structure of anxiety symptoms
      among children: a confirmatory factor-analytic study. Journal of Abnormal
      Psychology, 106, 280-297; Spence, S. H. (1998). A measure of anxiety symptoms
      among children. Behaviour Research and Therapy, 36, 545-566]), revised to
      correspond to dimensions of several DSM-IV anxiety disorders as well as major
      depression. This investigation involved initial evaluation of the factorial
      validity of the revised measure in a school sample of 1641 children and
      adolescents and reliability and validity in an independent sample of 246 children
      and adolescents. Results yielded an item set and factor definitions that
      demonstrated structure consistent with DSM-IV anxiety disorders and depression.
      The revised factor structure and definitions were further supported by the
      reliability and validity analyses. Some implications for assessment of childhood
      anxiety and depressive disorders are discussed.

PMID- 10937432
TI  - Conservation of a pseudomonad-like hydrocarbon degradative ferredoxin oxygenase
      complex involved in rhizopine catabolism in Sinorhizobium meliloti and Rhizobium
      leguminosarum bv. viciae.
AB  - In Sinorhizobium meliloti the mocCABR genes have previously been shown to be
      required for rhizopine (3-O-methyl-scyllo-inosamine, 3-O-MSI) catabolism. We show
      that the mocDE(F) gene cluster is also needed. MocDE(F), which is involved in the
      catabolism of 3-O-MSI to its demethylated form scyllo-inosamine (SI) has homology
      to components that would comprise a ferredoxin-oxygenase system. The mocCABRDE(F)
      suite of genes is required for 3-O-MSI catabolism in both S. meliloti and R.
      leguminosarum bv. viciae. However, SI catabolism in S. meliloti requires mocCABR,
      whereas only mocCA are required for its catabolism in R. leguminosarum suggesting
      the two species require different chromosomal genes which act in concert with moc
      genes for the catabolism of rhizopine.

PMID- 10937433
TI  - ATPase and GTPase activities copurifying with GTP-binding proteins in E. coli.
AB  - Intrinsic GTPase activity of GTP-binding proteins plays the vital role in
      regulating the downstream activation pathway. We examined the GTP and ATP
      hydrolyzing (NTPase) abilities of various bacterial and human GTP-binding
      proteins under different metabolic conditions. Two metabolic components, acetate
      and 3-phosphoglyceric acid (3-PG), have shown significant stimulatory action on
      NTPase activity of G-protein preparations. Acetyl phosphate and 2,3
      bisphosphoglyceric acid (2,3-BPG) blocked these stimulations. From gel filtration
      analyses, we have determined two fractions containing metabolite-inducible NTPase
      activities which are independent of GTP-binding protein enzymatic actions.
      Therefore, one should be cautious when NTPase activity is examined in a buffer
      containing acetate often used for NTPase assay.

PMID- 10937434
TI  - Identification of two genes encoding putative new members of the ECF subfamily of
      eubacterial RNA polymerase sigma factors in Clostridium acetobutylicum.
AB  - Two genes from Clostridium acetobutylicum DSM 792 were identified which are
      predicted to encode new members of the ECF subfamily of eubacterial RNA
      polymerase sigma factors. The sigX gene has the potential to encode a 184-amino
      acid protein with a molecular mass of 21,870 Da and with the highest overall
      similarity to Fecl of Escherichia coli (27 % identical residues). The second
      gene, which is predicted to encode an alternative sigma factor of the ECF
      subfamily, is the previously described orf2 gene (Gerischer and Durre, 1990)
      located in the adc gene region of C. acetobutylicum. The deduced protein of orf2
      has significant similarity to SigX of C. acetobutylicum (22 % identical residues)
      and shares structural features with other alternative sigma factors. Therefore,
      it is proposed to rename orf2 as sigY. Analysis of the phylogenetic relationship
      revealed that SigX from C. acetobutylicum, together with sigmaE from Streptomyces
      coelicolor and SigX from Bacillus subtilis, form a gram-positive cluster within
      the ECF subfamily and that SigY from C. acetobutylicum together with UviA from
      Clostridium perfringens, form a separate cluster located between the gram
      positive cluster and the sporulation sigma factor sigmaH from B. subtilis.

PMID- 10937435
TI  - Generation of hybrid elloramycin analogs by combinatorial biosynthesis using
      genes from anthracycline-type and macrolide biosynthetic pathways.
AB  - Elloramycin and oleandomycin are two polyketide compounds produced by
      Streptomyces olivaceus Tu2353 and Streptomyces antibioticus ATCC11891,
      respectively. Elloramycin is an anthracycline-like antitumor drug and
      oleandomycin a macrolide antibiotic. Expression in S. albus of a cosmid (cos16F4)
      containing part of the elloramycin biosynthetic gene cluster produced the
      elloramycin non-glycosylated intermediate 8-demethyl-tetracenomycin C. Several
      plasmid constructs harboring different gene combinations of L-oleandrose (neutral
      2,6-dideoxyhexose attached to the macrolide antibiotic oleandomycin) biosynthetic
      genes of S. antibioticus that direct the biosynthesis of L-olivose, L-oleandrose
      and L-rhamnose were coexpressed with cos16F4 in S. albus. Three new hybrid
      elloramycin analogs were produced by these recombinant strains through
      combinatorial biosynthesis, containing elloramycinone or 12a-demethyl
      elloramycinone (= 8-demethyl-tetracenomycin C) as aglycone moiety encoded by S.
      olivaceus genes and different sugar moieties, coded by the S. antibioticus genes.
      Among them is L-olivose, which is here described for the first time as a sugar
      moiety of a natural product.

PMID- 10937436
TI  - Prediction of two- and three-amino-acid sequences of Citrobacter Freundii beta
      lactamase from its amino acid composition.
AB  - The repeated amino-acid sequences in Citrobacter Freundii beta-lactamase may be
      indispensable for its function, because such repetitions cannot be simply
      attributed to a chance. In order to fully explore the functional units in
      Citrobacter Freundii beta-lactamase, it may need to analyse all the amino acid
      pairs, triplets, etc. along Citrobacter Freundii beta-lactamase from one terminal
      to the other terminal, to count their frequencies and calculate their
      probabilities. The amino-acid sequence of Citrobacter Freundii beta-lactamase was
      counted according to two-, three- and four-amino-acid sequences. The counted
      frequency and probability were compared with the predicted frequency and
      probability. The amino acid sequences, which appear in Citrobacter Freundii beta
      lactamase and can be predicted from its amino acid composition according to a
      purely random mechanism, should not be deliberately evolved and conserved. By
      contrast, the amino acid sequences, which appear in Citrobacter Freundii beta
      lactamase but cannot be predicted from its amino acid composition according to a
      purely random mechanism, should be deliberately evolved and conversed.
      Accordingly 99 (26.053%) and 33 (8.684%) of 380 two-amino-acid sequences can be
      predicted by the frequency and probability according to a purely random
      mechanism. Some kinds of amino acid sequences, which absent in Citrobacter
      Freundii beta-lactamase and can be predicted from its amino acid composition
      according to a purely random mechanism, should not be deliberately excluded from
      Citrobacter Freundii beta-lactamase. By contrast, some kinds of amino acid
      sequences, which absent in Citrobacter Freundii beta-lactamase and cannot be
      predicted from its amino acid composition according to a purely random mechanism,
      should be deliberately excluded from Citrobacter Freundii beta-lactamase.
      Accordingly 89 (48.370%) and 41 (22.283%) of 184 kinds of absent two-amino-acid
      sequences can be predicted by the frequency and probability according to a purely
      random mechanism, and 7236 (99.848%) of 7247 kinds of absent three-amino-acid
      sequences can be predicted by the frequency according to a purely random
      mechanism. The amino acids, whose probabilities in following certain preceding
      amino acids can be predicted from Citrobacter Freundii beta-lactamase amino acid
      composition according to a purely random mechanism, should not be deliberately
      evolved and conversed, accordingly 2 (0.526%) of 380 counted first order Markov
      transition probabilities for the second amino acid in two-amino-acid sequences
      match the predicted conditional probabilities.

PMID- 10937437
TI  - OmpT expression and activity increase in response to recombinant chloramphenicol
      acetyltransferase overexpression and heat shock in E. coli.
AB  - The activity of a 35 kDa protease increased in response to induced expression of
      chloramphenicol acetyltransferase (CAT) in E. coli. This protease was partially
      purified, extensively characterized, and identified via the use of zymogram gels
      as the outer membrane protease, OmpT. In experiments targeting the overlap of
      well-characterized stress responses, OmpT activity was found to increase in
      response to heat shock but was only minimally affected by amino acid limitation.
      The largest increase in activity was found after induction of CAT. OmpT
      expression levels also increased in response to induction of recombinant CAT
      overexpression and heat shock. This is the first report of increased activity and
      expression of an outer membrane protease during cytoplasmic overexpression of a
      recombinant protein.

PMID- 10937438
TI  - In vivo and in vitro analysis of RegA response regulator mutants of Rhodobacter
      capsulatus.
AB  - In the facultative photosynthetic bacterium Rhodobacter capsulatus, the
      transcription of genes encoding pigment binding proteins is tightly regulated in
      response to the oxygen partial pressure by the RegB/ RegA two component system.
      After a shift from high to low oxygen tension, the response regulator RegA
      enhances transcription of the puf and puc operon coding for the reaction center,
      light-harvesting complex I (LHI), and LHII proteins. Various regA mutant strains
      were analyzed in this study. In a RegA deficient strain, activation of puf and
      puc transcription is severely impaired which consequently leads to the synthesis
      of only a few photosynthetic complexes. Strains carrying a mutation in the helix
      turn-helix domain of RegA or a mutation of the phosphorylation site, Asp63, show
      a phenotype like the RegA deficient mutant, although the RegA(D63K) mutant
      protein showed the same DNA binding behavior as the wild type protein. In
      contrast, the puf and puc mRNAs still reach about 50-70 % of the wild type level
      after reduction of oxygen tension in strains which synthesize the C-terminal RegA
      activator domain only or a hybrid protein composed of the RegA activator and the
      FixJ receiver domain, while both mutant proteins are impaired in DNA binding. Our
      data suggest that phosphorylation is not required for DNA binding but rather
      plays a role for efficient initiation of transcription.

PMID- 10937439
TI  - Role of DNA methylation at GATC sites in the dnaA promoter, dnaAp2.
AB  - DnaA protein is required for the initiation of DNA replication at the bacterial
      chromosomal origin, oriC, and at the origins of many plasmids. The concentration
      of DnaA protein is an important factor in determining when initiation occurs
      during the cell cycle. Methylation of GATC sites in the dnaAp2 promoter, two of
      which are in the -35 and -10 sequences, has been predicted to play an important
      role in regulating dnaA gene expression during the cell cycle because the
      promoter is sequestered from methylation immediately following replication.
      Mutations that eliminate these two GATC sites but do not substantially change the
      activity of the promoter were introduced into a reporter gene fusion and into the
      chromosome. The chromosomal mutants are able to initiate DNA replication
      synchronously at both moderately slow and fast growth rates, demonstrating that
      GATC methylation at these two sites is not directly involved in providing the
      necessary amount of DnaA for precise timing of initiation during the cell cycle.
      Either sequestration does not involve these GATC sites, or cell cycle control of
      DnaA expression is not required to supply the concentration necessary for correct
      timing of initiation.

PMID- 10937440
TI  - Phosphoenolpyruvate is a signal metabolite in transcriptional control of the cbb
      CO2 fixation operons in Ralstonia eutropha.
AB  - The two highly homologous cbb operons of the facultative chemoautotroph Ralstonia
      eutropha H16 encode most enzymes of the Calvin-Benson-Bassham carbon reduction
      cycle. Their transcriptional regulation was investigated both in vitro and in
      vivo to identify a metabolic signal involved in this process. For this purpose an
      in vitro transcription system employing the DNA-dependent RNA polymerase purified
      from R. eutropha was established. The enzyme from Escherichia coli was also used
      in verifying comparative studies. Plasmid DNA carrying the control region of the
      chromosomal cbb operon served as template. In the homologous as well as the
      heterologous system specific transcripts synthesized under the control of the
      operon promoter PcbbL were observed, depending on the structure of the tested
      promoter variant as well as the presence or absence of the activator protein
      CbbR. Unlike mutationally improved PcbbL variants, the wild-type promoter
      remained inactive, even in the presence of CbbR together with various potential
      signal metabolites. CbbR stimulated PcbbL mutants with intermediate basal
      activity. Phosphoenolpyruvate (PEP) was identified as a negative effector of CbbR
      that inhibited PcbbL-directed transcription and increased the operator-binding
      affinity of the protein. This CbbR-mediated inhibition was confirmed by assaying
      wild-type PcbbL operon fusions in glucose- or succinate-grown cells of E. coli,
      which contain greatly different concentrations of PEP. It is concluded that at
      least one additional protein must participate in the overall control of the cbb
      operons in R. eutropha.

PMID- 10937441
TI  - Modeling of Enterococcus faecalis D-alanine:D-alanine ligase: structure-based
      study of the active site in the wild-type enzyme and in glycopeptide-dependent
      mutants.
AB  - A model for the 3-D structure of Enterococcus faecalis D-Ala:D-Ala ligase was
      produced using the X-ray structure of the Escherichia coli enzyme complexed with
      ADP and the methylphosphinophosphate inhibitor as a template. The model passed
      critical validation criteria with an accuracy similar to that of the template
      crystallographic structure and showed that ADP and methylphosphinophosphate were
      positioned in a large empty pocket at the interface between the central and the C
      terminal domains, as in E. coli. It evidenced the residues important for
      substrate binding and catalytic activity in the active site and demonstrated a
      large body of conserved interactions between the active sites of the E. faecalis
      and the E. coli D-Ala:D-Ala ligase, the major differences residing in the balance
      between the hydrophobic and aromatic environment of the adenine. The model also
      successfully explained the inactivity of four spontaneous mutants (D295 --> V,
      which impairs interactions with Mg2+ and R293, which are both essential for
      binding and catalytic activity; S319 --> I, which perturbs recognition of D-Ala2;
      DAK251-253 --> E, in which the backbone conformation in the vicinity of the
      deletion remains unaltered but phosphate transfer from ATP is perturbed because
      of lack of K253; T316 --> I, which causes the loss of a hydrogen bond affecting
      the positioning of S319 and therefore the binding of D-Ala2). Since D-Ala:D-Ala
      ligase is an essential enzyme for bacteria, this approach, combining molecular
      modeling and molecular biology, may help in the design of specific ligands which
      could inhibit the enzyme and serve as novel antibiotics.

PMID- 10937442
TI  - Expression of the gene for the delta9 acyl-lipid desaturase in the thermophilic
      cyanobacterium.
AB  - A single-copy gene resembling the gene for the delta9 acyl-lipid desaturase
      (desC) was cloned from the thermophilic cyanobacterium Synechococcus vulcanus.
      Expression of desC in Escherichia coli confirmed that it encodes the delta9
      desaturase. The nucleotide sequence of the desC was characterized by high G+C
      content that is typical of the sequences of thermophilic bacteria. The deduced
      amino acid sequence exhibited low Cys content and high Arg/Lys ratio that are the
      attributes of thermostable enzymes. A low level of the desC mRNA was detected in
      the cells grown at 55 degrees C, the optimum growth temperature for S. vulcanus.
      About a 10-fold increase was observed in the levels of the transcript and the
      protein during the shift in temperature from 55 to 45 degrees C. At 35 degrees C
      the amount of the desC mRNA and of the enzyme accumulated in the cells, was 3 to
      4 times smaller than at 45 degrees C. At both temperatures, however, lipids were
      desaturated at similar rates. These results suggest that in S. vulcanus the
      conversion of stearic acid into oleic acid may be controlled not only by the de
      novo synthesis of the delta9 desaturase but, possibly, by the activation of the
      pre-existing enzyme.

PMID- 10937443
TI  - Effect of over-the-counter drugs on the unborn child: what is known and how
      should this influence prescribing?
AB  - The developing organism is unique in its responsiveness to drugs. The
      predictability of therapeutic effectiveness and safety of drugs in pregnancy
      using the adult as a model for pharmacokinetics and pharmacodynamics can result
      in grave consequences in the fetus. There exists a general misconception that
      since over-the-counter (OTC) drugs are readily available, these pharmaceutical
      agents can be viewed as safe to use by adults. Ingestion of OTC preparations
      during pregnancy results in placental transfer and accumulation of these drugs in
      the fetus. As the fetus lacks the ability to handle pharmaceutical agents, since
      renal function, metabolic pathways, etc. are not fully developed, drug exposure
      in utero may produce deleterious effects in the fetus but not the mother.
      Clinicians are aware of drug-induced effects on the fetus and have dramatically
      reduced the use of prescription drugs during pregnancy. However, the use of self
      medication (OTC) has significantly increased during pregnancy through extensive,
      effective advertising by the pharmaceutical industry and lack of sufficient data
      indicating an OTC effect on the fetus. However, the consequences of OTC drug use
      need to be established, since these compounds continue to be used extensively,
      especially during pregnancy.

PMID- 10937444
TI  - Patent ductus arteriousus in the premature neonate: current concepts in
      pharmacological management.
AB  - In utero, the ductus arteriosus shunts deoxygenated blood away from the pulmonary
      artery and towards the placental circulation where foetal gas exchange occurs. As
      a result of an intricately intertwined network of both physiological and
      biochemical changes, this vessel constricts rapidly after birth. Deoxygenated
      blood is diverted away from the placenta and through the lungs now vital for gas
      exchange. Premature closure of the ductus in utero can cause pulmonary
      hypertension and even death. Conversely, failure to close after birth can
      exacerbate respiratory distress, precipitate congestive heart failure and
      increase the risk of subsequent intestinal ischaemia leading to necrotising
      enterocolitis, bronchopulmonary dysplasia, renal hypoperfusion and/or cerebral
      ischaemia. In this review we summarise current knowledge of the delicately
      orchestrated control of the ductus arteriosus, focusing on the role of cyclo
      oxygenase isoforms on prostaglandin production, on the interaction between
      prostaglandins and oxygen, and on the effects of these on ductal patency. We also
      seek to describe some of the standard and nonstandard therapeutic approaches
      available to the clinician when natural closure fails, reviewing alternative
      protocols for indomethacin administration and comparing indomethacin treatment
      with newer approaches such as ibuprofen. In summary, we will follow the course of
      this unique blood vessel as it is transformed over several hours from an organ
      absolutely vital to survival into programmed obsolescence.

PMID- 10937445
TI  - Common errors of drug administration in infants: causes and avoidance.
AB  - Drug administration errors are common in infants. Although the infant population
      has a high exposure to drugs, there are few data concerning pharmacokinetics or
      pharmacodynamics, or the influence of paediatric diseases on these processes.
      Children remain therapeutic orphans. Formulations are often suitable only for
      adults; in addition, the lack of maturation of drug elimination processes,
      alteration of body composition and influence of size render the calculation of
      drug doses complex in infants. The commonest drug administration error in infants
      is one of dose, and the commonest hospital site for this error is the intensive
      care unit. Drug errors are a consequence of system error, and preventive
      strategies are possible through system analysis. The goal of a zero drug error
      rate should be aggressively sought, with systems in place that aim to eliminate
      the effects of inevitable human error. This involves review of the entire system
      from drug manufacture to drug administration. The nuclear industry,
      telecommunications and air traffic control services all practise error reduction
      policies with zero error as a clear goal, not by finding fault in the individual,
      but by identifying faults in the system and building into that system mechanisms
      for picking up faults before they occur. Such policies could be adapted to
      medicine using interventions both specific (the production of formulations which
      are for children only and clearly labelled, regular audit by pharmacists, legible
      prescriptions, standardised dose tables) and general (paediatric drug trials,
      education programmes, nonpunitive error reporting) to reduce the number of errors
      made in giving medication to infants.

PMID- 10937446
TI  - Sedation and analgesia in paediatric intensive care units: a guide to drug
      selection and use.
AB  - The indications for sedation in the paediatric intensive care unit (PICU) patient
      are varied ranging from short term use for various procedures to prolonged
      administration to provide comfort during mechanical ventilation. When faced with
      the decision to institute sedation, the healthcare provider must make three
      decisions: the agent to be used, the route of delivery, and the mode of
      administration (intermittent versus continuous). There are several agents that
      have been used to provide sedation in the PICU patient including the inhalational
      anaesthetic agents, benzodiazepines, opioids, ketamine, propofol, chloral
      hydrate, phenothiazines, and the barbiturates. This review describes the various
      agents for sedation and discusses their advantages and disadvantages as they
      pertain to the PICU. Consequences of and treatment strategies for long term
      problems with prolonged sedation including tolerance, physical dependency, and
      withdrawal are reviewed.

PMID- 10937448
TI  - Clinical use of somatomedin-1: yes or no?
AB  - Insulin-like growth factor-I (IGF-I) is a polypeptide of 70 amino acids. The
      circulatory form of IGF-I is synthesised in the liver. The metabolic activity of
      IGF-I is regulated by 6 IGF binding proteins. the most important being IGF
      binding protein-3. IGF-I acts via its own receptor, which resembles that of
      insulin. It has been demonstrated that the effects of pituitary growth hormone
      (GH, somatropin) on protein metabolism, including growth and effects on nervous
      and renal tissue, are mediated by IGF-I, whereas these 2 hormones are
      antagonistic in their effects on insulin and some aspects of lipid metabolism.
      The biosynthesis of recombinant human IGF-I (somatomedin-1) in 1986 enabled the
      initiation of clinical trials. The most important involves replacement therapy in
      primary IGF-I deficiency, such as Laron syndrome (primary GH resistance or
      insensitivity), and in patients who have developed antibodies to human GH. In
      Laron syndrome, which is characterised by dwarfism, somatomedin-1 stimulates
      growth and increases muscle and bone mass, as well as normalising blood
      chemistry. In diabetes mellitus types 1 and 2 (insulin-dependent and non-insulin
      dependent), somatomedin-1 increases the sensitivity to insulin and improves
      glucose utilisation, and may contribute to healing of injured nerve tissue and
      improve renal function in humans. Adverse effects of somatomedin-1 appear to be
      related to overdosage. In conclusion, somatomedin-1 is an important hormone which
      has clinical roles as replacement therapy and other pharmacological therapies.

PMID- 10937447
TI  - Sevoflurane in paediatric anaesthesia: a review.
AB  - Sevoflurane is an ether inhalation anaesthetic agent with low pungency, a non
      irritant odour and a low blood: gas partition coefficient. It can be rapidly and
      conveniently administered without discomfort, and its low solubility facilitates
      precise control over the depth of anaesthesia and a rapid and smooth induction
      of, and emergence from, general anaesthesia. As an induction and maintenance
      agent for ambulatory and nonambulatory surgery in children, sevoflurane provides
      more rapid induction of, and emergence from, anaesthesia than halothane, and has
      similar or better patient acceptability. Time to discharge from the recovery area
      is usually at least as fast with sevoflurane as with halothane. While rapid
      emergence from sevoflurane lessens the time spent under anaesthesia,
      postoperative pain may be more intense and occur earlier than during more gradual
      emergence. Sevoflurane has been used successfully as an induction agent for
      tracheal intubation and laryngeal mask airway (LMA) insertion: time to LMA
      insertion is faster with sevoflurane than halothane, but the 2 drugs provide
      similar conditions for tracheal intubation. The pattern and incidence of
      induction and emergence events such as cough, laryngospasm and
      agitation/excitement is similar with sevoflurane and halothane; however,
      sevoflurane may cause less postoperative nausea and vomiting. At present,
      differences have not been consistently shown between the 2 drugs in their
      propensity to cause postoperative excitement or agitation. Compared with
      halothane, sevoflurane has low potential for arrhythmogenicity. Clinical
      experience does not substantiate concerns over the potential nephrotoxicity of
      the sevoflurane byproducts pentafluoroisopropenyl fluoromethyl ether ('Compound
      A') and plasma F- ions; no renal impairment has been documented in children
      receiving sevoflurane in clinical trials. The potential for sevoflurane
      hepatotoxicity also appears negligible. There are few trials comparing
      sevoflurane with agents other than halothane in paediatric anaesthesia. As well,
      pharmacoeconomic analyses are scarce and incompletely published; further studies
      are needed to determine whether shortened times to emergence will translate into
      cost savings. CONCLUSION: Sevoflurane is a preferred anaesthetic agent for
      induction and maintenance of paediatric anaesthesia because of its rapid
      induction and recovery characteristics, lack of pungency and agreeable odour, and
      acceptable cardiovascular profile. Although the issue of postoperative excitement
      requires clarification, sevoflurane anaesthesia can be considered a rational
      choice for ambulatory and nonambulatory surgery in children.

PMID- 10937450
TI  - Therapeutics of aggression in children.
AB  - This paper examines the phenomenology, aetiology and therapeutics of childhood
      aggression that arises as part of a disruptive behaviour disorder. Phenomenology
      is discussed with an emphasis on treatment implications. Reviewed studies show
      that aggressive behaviour exhibits both episodicity and considerable individual
      stability. Aetiological theories are reviewed with emphasis on the interplay
      between biological and socio-environmental factors. Both factors are centrally
      involved in the development and treatment of aggression. A review of double
      blind, placebo-controlled medication studies is presented. A computer-based,
      literature search using Medline and PsychInfo was conducted to locate all
      potentially relevant articles published in the past 20 years. It was found that
      there are various treatments available for reducing paediatric aggression
      including psychotherapeutic and psychopharmacological treatments. There are data
      to support the use of psychostimulants, lithium and antipsychotics, while data
      for other agents are only beginning to accumulate. Various pharmacological
      treatments can reduce aggression in children. However, given the role of both
      biological and social factors in the development of aggression, multimodal
      treatment may ultimately provide maximal benefits.

PMID- 10937452
TI  - Prevention and treatment of head lice in children.
AB  - Head louse infestations (pediculosis) are prevalent worldwide. In developed
      countries, the infestation rate of 4- to 13-year-old children remains high
      despite preventive efforts. This is due to the existence of numerous ineffective
      pediculicides, the incorrect use of the effective agents, toxicological concerns
      and the development of louse strains resistant to insecticides. One of the most
      effective tools for the prevention and control of lice is the louse comb, which
      should be used regularly for the detection of living lice at an early stage of
      infestation, and as an accessory to any treatment method to remove living and
      dead lice. The louse comb can also be used systematically for the treatment of
      infestations, for confirmation that treatment with pediculicides has been
      successful, and for the removal of nits (dead eggs or egg shells). Most
      pediculicides are only partially ovicidal. Therefore, 10 days after beginning
      treatment with any antilouse product, the scalp of the child should be examined.
      If no living lice are found, the treatment should be discontinued. If living lice
      are still present, treatment should be continued with a product containing a
      different active ingredient. Suffocating agents such as olive, soya, sunflower
      and corn oils, hair gels and mayonnaise are able to kill a significant number of
      lice only if they are applied in liberal quantities for more than 12 hours.
      However, they lubricate the hair and therefore may facilitate combing and
      removing lice and eggs from the scalp. Nits may remain glued on the hair for at
      least 6 months, even after a successful treatment, and lead to a false positive
      diagnosis of louse infestation. If nits are seen on the hair, the child should be
      examined, but treatment should be initiated only if living lice are found.
      Formulations containing 5% acetic acid or 8% formic acid, as well as acid
      shampoos (pH 4.5 to 5.5) and conditioners, in combination with a louse comb, can
      be helpful for removing nits. There is no conclusive evidence that using
      essential oils to repel lice is effective. Regular examination of the child's
      head using a louse comb is the best measure to detect re-infestation at an early
      stage. Educating caregivers, nurses and teachers about louse biology,
      epidemiology, prevention and control is of paramount importance. The
      psychological effect of an infestation with lice is significant and often
      associated with anxiety and fear. The child should not be made to feel
      responsible for having lice, or be punished or reprimanded.

PMID- 10937451
TI  - Chemotherapy of childhood lymphoblastic leukaemia: the first 50 years.
AB  - It is 50 years since the first effective drug for childhood lymphoblastic
      leukaemia (ALL) was described. At that time the outlook for such children was
      certain death. Now patients have an odds-on chance of normal health and life
      expectancy. Although the greatest gains have been made in recent years, the
      classes of drug that have achieved this have all been available for over 20
      years. It is their better deployment and the greater understanding of their
      pharmacology that have allowed both more effective protocols to be devised and
      long term adverse effects to be recognised and avoided. Supportive treatment has
      also improved in parallel. Three major problems remain: (i) how to recognise
      children in whom conventional therapy will fail; (ii) how to prevent failure; and
      (iii) how to treat it if it occurs. Therapy will fail in some children for
      pharmacological reasons--noncompliance or constitutional (genetic) drug
      resistance. For such children in vitro drug sensitivity testing and greater
      pharmacological vigilance may help by identifying those at risk and allowing
      intervention. In others, treatment will fail because of intrinsically resistant
      disease that either develops despite therapy or regrows from a minimal residue.
      Despite wider application of sophisticated immunological and genetic studies both
      at diagnosis or later, recognising poor-prognosis children prospectively is
      hampered by the lack of a biological classification system that is sufficiently
      sensitive and specific to categorise all patients reliably. In those where there
      is no doubt about high-risk status, treatment failure rates are still
      unacceptably high whatever therapy is given, and salvage therapy in any child who
      relapses is a continuing challenge.

PMID- 10937449
TI  - Pharmacological treatment of depression in children and adolescents.
AB  - Major depression is a common disorder during childhood and adolescence. Over the
      past decade, many new antidepressants have been marketed in the US. In adults,
      these newer agents have been shown to be as effective as the prototypic tricyclic
      antidepressants (TCAs). Further, when compared with the TCAs these medications
      are better tolerated and are safer in overdose. Although TCAs are effective in
      the treatment of depressed adults, controlled clinical trials have not
      demonstrated their efficacy in either children or adolescents. In addition,
      concerns about the safety of TCAs and the monoamine oxidase inhibitors has left
      disappointingly few pharmacological treatment options available for depressed
      children and adolescents. For this reason, clinicians have begun to prescribe the
      newer agents for this population, despite the fact that relatively little is
      known about their disposition, safety or effectiveness in the young.
      Investigators have begun to examine whether the use of newer antidepressant
      medications such as fluoxetine, sertraline, paroxetine, fluvoxamine, nefazodone,
      and venlafaxine is truly indicated for children and adolescents with major
      depression. Pharmacokinetic studies of sertraline, paroxetine and nefazodone have
      been performed in depressed youths. The results of these studies have provided
      data for rational administration strategies for these agents. They have also
      provided evidence that these agents may be well tolerated in children and
      adolescents. Further evidence that these agents are often well tolerated when
      prescribed to depressed youths has been obtained from both open-label and double
      blind studies. Published studies have generally shown that open-label treatment
      with these newer agents often leads to symptom amelioration in paediatric
      patients with major depression. Since high rates of placebo response are often
      seen in depressed children and adolescents, results from these studies cannot be
      interpreted to suggest that these medications have true antidepressant efficacy
      in this population. At present, the results of only two such studies have been
      published. The results of one of these trials are difficult to interpret because
      of methodological considerations. The other study reported that treatment with
      fluoxetine was superior to placebo. This paper critically reviews what has been
      published about the pharmacological treatment of depressed paediatric patients
      and provides some guidance to the use of antidepressants in this patient
      population, paying particular attention to what is known about the newer
      antidepressants as well as considering directions for future research.

PMID- 10937453
TI  - Calfactant: a review of its use in neonatal respiratory distress syndrome.
AB  - Calfactant (Infasurt) is a natural bovine surfactant which has been evaluated for
      intratracheal use in the prevention and rescue treatment of respiratory distress
      syndrome (RDS) in preterm infants. In 2 randomised, double-blind, multicentre
      clinical trials of prophylactic use, calfactant 100 or 105 mg phospholipid per kg
      bodyweight (mg/kg) reduced RDS incidence, RDS severity and mortality rates to a
      greater extent than colfosceril palmitate (Exosurf Neonatal) 67.5 mg/kg and was
      generally similar to beractant (Survanta) 100 mg/kg. Although the rate of
      mortality before discharge from hospital was significantly higher in infants with
      birthweights <600 g who received calfactant than in those who received beractant,
      this may not be a typical result. As rescue treatment, calfactant 100 or 105
      mg/kg reduced RDS severity, but not mortality rates, significantly more than
      colfosceril palmitate 67.5 mg/kg or beractant 100 mg/kg in 2 randomised, double
      blind, multicentre clinical trials. In addition, the duration of effect of
      calfactant as prophylaxis or rescue treatment appeared to be longer than that of
      beractant. In other randomised trials, prophylaxis was more effective than rescue
      treatment with calfactant, particularly in infants of < or =29 weeks gestational
      age. The incidence of pulmonary air leak events was lower with calfactant than
      with colfosceril palmitate (12 vs 22%) but was identical with calfactant and
      beractant (15% with either agent). The incidence of other complications
      associated with RDS was usually similar with all 3 agents in clinical trials in
      preterm infants. The incidence of intraventricular haemorrhage was significantly
      higher in 1 clinical trial, and that of septicaemia was significantly lower in
      another, with calfactant versus colfosceril palmitate, but the combined
      incidences of these complications was similar with the 2 agents when results from
      different trials were pooled. The incidence of acute adverse events (i.e. those
      which occurred during administration of the drug) with calfactant was similar to
      that with beractant and higher than that with colfosceril palmitate; the
      difference may been related to reduced RDS severity in calfactant versus
      colfosceril palmitate recipients. Acute adverse events were usually transient and
      not severe. CONCLUSIONS: Calfactant is a well tolerated natural bovine surfactant
      which is effective in the prevention and treatment of RDS in preterm infants.
      Further investigation is needed to more clearly determine the efficacy and
      tolerability of calfactant relative to that of other surfactant preparations.
      When more data are available, it is likely that calfactant will be useful as an
      alternative to beractant (at least in infants of birthweights >600 g), and
      calfactant may be preferred over colfosceril palmitate in both the prophylaxis
      and treatment of RDS.

PMID- 10937454
TI  - Narcolepsy in children: a practical guide to its diagnosis, treatment and follow
      up.
AB  - Narcolepsy is a neurological syndrome characterised by daytime somnolence and
      cataplexy which often begins in childhood. Failing to recognise the condition may
      lead to mislabelling a child as lazy or depressed. The diagnostic criteria for
      narcolepsy vary with age. In children 8 years and older a Multiple Sleep Latency
      Test with an average latency of less than 8 minutes, and 2 or more sleep onset
      REM episodes supports the diagnosis. Human leucocyte antigen (HLA) marker DQbeta1
      -0602 has been associated with narcolepsy. The current evidence supports the
      hypothesis that transmission of narcolepsy is multifactorial. with at least two
      genes, one of which is non-HLA related. The goal of all therapeutic approaches in
      narcolepsy is to control the narcoleptic symptoms and allow the patient to
      continue to fully participate in personal and academic activities. This usually
      requires a combination of behavioural therapy along with medication. Medications
      for patients with excessive sleepiness are usually stimulants, including
      amphetamines. However, a novel wake promoting agent, modafinil, is now available.
      Cataplexy can be controlled by medications with noradrenergic reuptake-blocking
      properties, such as clomipramine and fluoxetine, through their active
      metabolites. Increased awareness of narcolepsy is important to allow earlier
      diagnosis. Research on the effects different medications have, specifically on
      children with narcolepsy, has been very limited.

PMID- 10937456
TI  - Antipsychotics and breast-feeding: a review of the literature.
AB  - Many women with mental illnesses would like to breast feed their infants. In
      light of the limited but rapidly growing data, it seems that in some cases the
      possible physiological and psychological benefits may outweigh putative risks.
      All antipsychotics are secreted into breast milk but the concentrations and
      effects vary. There is a subgroup of mothers with mental illnesses who want to
      breast feed their infants and who are receiving a single established
      antipsychotic drug (principally, haloperidol or chlorpromazine) at the lowest
      possible clinically effective dose. As a tentative conclusion, this group could
      experience benefits from being able to nurse which would outweigh the risk of
      exposing their babies to very small amounts of antipsychotic drugs. However,
      larger study groups with longer follow-up periods would be required to confirm
      this tentative conclusion. Those mothers who require 2 or more antipsychotic
      drugs simultaneously and those taking one drug, but at the upper end of the
      recommended dose range, should not be advised to breast feed. Safety
      considerations suggest that women taking atypical antipsychotics would be advised
      not to breast feed because of the limited experience with these agents. When
      mothers taking antipsychotic drugs do nurse, it is desirable to monitor drug
      concentrations in breast milk and in the infants themselves. Close monitoring of
      the infant is essential.

PMID- 10937455
TI  - Role of lipid-lowering pharmacotherapy in children.
AB  - For patients with coronary artery disease and healthy middle-aged or older
      individuals with elevated cholesterol levels, treatment with cholesterol-lowering
      drugs reduces morbidity and sometimes mortality. Treatment reverses established
      atherosclerotic lesions within a relatively short period of time, suggesting that
      starting cholesterol-lowering drugs in adulthood is adequate for most people at
      risk. Children with genetic lipid disorders, including familial
      hypercholesterolaemia and familial combined hyperlipidaemia, may be candidates
      for earlier therapy. A complete assessment of risk factors should be undertaken
      to determine which children are at highest risk. Treatment should start with
      diet, because diet is an important independent protective factor for disease. The
      bile acid sequestrants (resins) are the only drugs approved for children and may
      reduce low density lipoprotein (LDL)-cholesterol levels by 15 to 20% at best.
      Long term tolerability is good, but many children will not take the resins
      because they find them unpalatable. Tablet formulations have higher
      acceptability. Some children require supplementation with fat soluble vitamins or
      folate. Although hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
      have not been tested in long term studies in children, safety records are
      excellent in adults. Short term studies show that HMG-CoA reductase inhibitors
      reduce LDL-cholesterol levels similarly in children and in adults. Thus, the
      drugs may be used in low dosages to treat some adolescents with exceptional risk
      of disease.

PMID- 10937458
TI  - Common brain tumours in children: diagnosis and treatment.
AB  - Dramatic advances have been made in the diagnosis of childhood brain tumours
      thanks to the development of modern imaging techniques. Advances in the
      management of these tumours have, however, been slow because of the limitations
      of an aggressive surgical approach and the risks associated with radiotherapy on
      the growing, and still immature, brain. The role of chemotherapy remains ill
      defined in many patients with brain tumours and large variations in practice
      exist between groups and institutions. This article provides an overview of the
      most common paediatric brain tumours, mainly gliomas, medulloblastomas,
      ependymomas, germ-cell tumours and craniopharyngiomas. Considerations regarding
      the management of brain tumours in very young children are also examined. The
      long term outcome for children with brain tumours is discussed, stressing the
      need to focus on quality of life for survivors.

PMID- 10937459
TI  - Autism: current theories regarding its pathogenesis and implications for rational
      pharmacotherapy.
AB  - Autism is a pervasive developmental disorder that is aetiologically and
      clinically heterogeneous. Twin and family-genetic studies provide evidence for
      strong genetic components. An international consortium using an affected sib pair
      strategy has found a promising linkage to a region on chromosome 7. In 10 to 15%
      of cases autism is due to associated medical conditions that affect normal brain
      functioning. Postmortem studies on small case series report cellular
      abnormalities in the limbic system and cerebellum. Between 10 and 20% of
      individuals with autism have macrocephalia, which is in accordance with magnetic
      resonance imaging (MRI) findings of an increased total brain tissue volume and
      enlargement most prominent in the occipital and parietal lobes. The most robust
      and well replicated neurobiological abnormality in autism is an elevation of
      whole blood serotonin (5-hydroxytryptamine; 5-HT) found in over 30% of patients.
      Pharmacological interventions with serotonin reuptake inhibitors or with atypical
      neuroleptics that block both dopamine (D2) and serotonin (5-HT2) receptors seem
      to offer clinical benefit and merit further study.

PMID- 10937457
TI  - Management of graft-versus-host disease in paediatric bone marrow transplant
      recipients.
AB  - We discuss clinical strategies for the prophylaxis and treatment of both acute
      and chronic graft-versus-host disease (GVHD) with particular attention to
      children. Grades II to IV acute GVHD occur in 10 to 50% of patients given an
      allogeneic transplantation of haemopoietic stem cells (HSCT) from a genotypically
      HLA-identical donor. A significantly higher incidence and severity of the disease
      is reported in patients receiving transplants from partially matched family
      donors or unrelated volunteers. Younger individuals or patients receiving HSCT
      from younger donors develop GVHD less frequently than do older recipients. Severe
      acute GVHD is characterised by a significant decrease in survival probability,
      even though the graft-versus-leukaemia activity associated with both acute and
      chronic GVHD may reduce the risk of leukaemia relapse. Prophylaxis of acute GVHD
      usually consists of in vivo post-grafting immunosuppression with cyclosporin
      alone or in combination with methotrexate; methotrexate alone can be considered
      in leukaemia patients with a high risk of relapse. In recent years, tacrolimus is
      increasingly being used instead of cyclosporin, alone or in combination with
      methotrexate. In vitro T cell depletion in paediatric patients is usually
      reserved for those with transplants from partially matched family donors or
      unrelated volunteers. The treatment of patients with grades II to IV acute GVHD
      should be immediate and aggressive, as the quality and duration of the response
      directly correlates with survival. The overall response rate to treatment is
      often unsatisfactory, ranging from 40 to 50% of cases. First-line treatment
      usually consists of corticosteroids. In patients not responding to
      corticosteroids, antilymphocyte globulin and monoclonal antibodies directed
      towards lymphocytes and/or cytokines produced during GVHD are employed, but with
      variable success. Patients experiencing acute GVHD are also prone to develop
      chronic GVHD. whose classical treatment is based on the use of cyclosporin and
      corticosteroids. More recently, encouraging results in the treatment of patients
      with chronic GVHD have been reported with the use of extracorporeal
      photochemotherapy. Other drugs, such as ursodeoxycholic acid, etretinate and
      clofazimine, are under evaluation.

PMID- 10937460
TI  - Effects of antipsychotics on the unborn child: what is known and how should this
      influence prescribing?
AB  - The onset of psychosis during pregnancy presents difficult management decisions.
      A complete and thorough physical and obstetric examination is always warranted to
      look for possible physiological precipitants. The treatment of pregnant patients
      with psychotic symptomatology requires close contacts between family members, non
      physician professionals involved in the patient's care (e.g. social workers, case
      managers and home healthcare nurses), and the physicians overseeing the patient's
      management (e.g. internists, obstetricians and psychiatrists). In mild and less
      disabling cases it may be possible to avoid medication intervention but this
      approach risks adverse behaviour consequences resulting from a possible worsening
      of the patient's symptomatology. Avoiding medication requires an environment in
      which the patient has strong social supports. Risks are present whether
      medication is initiated or not, and treatment decisions require a careful
      assessment of the risks and benefits involved. Initiating medication raises the
      possibility of obstetric, teratogenic, neurobehavioural and neonatal toxic
      effects. Research on the risks imposed by antipsychotic drug use during pregnancy
      is incomplete and raises questions regarding appropriate management. The first
      trimester represents a period of increased susceptibility to medication-induced
      teratogenesis. The use of low potency phenothiazines during the first trimester
      may increase the risk of congenital abnormalities by an additional 4 cases per
      1000 (odds ratio = 1.21, p = 0.04) The pharmacological profiles of antipsychotic
      medications also present adverse effects which need to be considered during
      pregnancy (hypotension, sedation, etc.). Less is known about the risk of adverse
      consequences resulting from the use of newer atypical antipsychotic medications.
      Electroconvulsive therapy is another treatment modality and its use may
      circumvent the need to introduce antipsychotic medication during pregnancy. It
      must be stressed that. given current knowledge, no treatment regimen can be
      considered completely safe. Ultimately many factors must be evaluated when
      treating psychosis during pregnancy, however, no decision is risk-free.

PMID- 10937461
TI  - The role of drug treatment in children with strabismus and amblyopia.
AB  - Strabismus, or misalignment of the eyes, is a common ophthalmic problem in
      childhood, affecting 2 to 5% of the preschool population. Amblyopia is an
      important cause of visual morbidity frequently associated with strabismus, and
      both conditions should be treated simultaneously. Pharmacological means for
      treating strabismus and amblyopia can be divided into 3 categories: paralytic
      agents (botulinum toxin) used directly on the extraocular muscles to affect eye
      movements; autonomic agents (atropine, miotics) used topically to manipulate the
      refractive status of the eye and thereby affect alignment, focus and amblyopia;
      and centrally acting agents, including levodopa and citicoline, which affect the
      central visual system abnormalities in amblyopia. Botulinum toxin, the paralytic
      agent that causes the clinical symptoms of botulism poisoning, can be injected in
      minute quantities to achieve controlled paralysis of the extraocular muscles.
      Although the role of botulinum toxin is established in adults with paralytic
      strabismus, its usefulness in the treatment of comitant childhood strabismus
      (primary esotropia and exotropia) is not universally accepted. Botulinum
      injections tend to be more effective with smaller degrees of strabismus, in
      patients with good binocular fusion, and in managing overcorrections or
      undercorrections after traditional muscle surgery. Inadvertent ptosis and
      paralysis of adjacent muscles, unpredictable responses and technical constraints
      of the injections limit its use in children. Miotic therapy, by altering the
      refractive state of the treated eye, offers an alternative to optical correction
      with bifocals in treating esotropia due to excessive accommodative convergence.
      It is also effective in treating residual esotropia following surgery. The ease
      of use of glasses restricts the wide application of miotics in these common
      strabismus syndromes. Atropine, an anticholinergic agent, paralyses the ability
      of the eye to focus or accommodate. In amblyopia therapy, atropine is used to
      blur vision in the non-amblyopic eye and offers a useful alternative to
      traditional occlusion therapy with patching, especially in older children who are
      not compliant with patching. The neurotransmitter precursor levodopa and the
      related compound citicoline have been demonstrated to improve vision in amblyopic
      eyes. The therapeutic role of these centrally acting agents in the clinical
      management of amblyopia remains unproven.

PMID- 10937464
TI  - Respiratory syncytial virus immunoprophylaxis: impact on epidemiology.
AB  - OBJECTIVE: To better understand the spectrum of disease among hospitalised
      children infected with respiratory syncytial virus (RSV) and to assess the
      potential impact of passive immunoprophylaxis on RSV hospitalisation rates, we
      analysed all patients infected with RSV who were admitted to a paediatric
      teaching hospital over a 3-year period. DESIGN: We performed a retrospective
      chart review of all paediatric patients from whom RSV was isolated between
      October 1, 1994 and April 30, 1997. RESULTS: A total of 255 children infected
      with RSV were hospitalised during this 3-year period. 246 (96%) patients had
      community acquired infections and 9 (4%) had nosocomial infections. Excluding
      patients with nosocomial infections, the mean length of hospital stay was 4.7
      days. 70 (28%) children were admitted to the intensive care unit, 32 (13%) were
      intubated and there was a total of 4 deaths (1.6%). 48% of hospitalised patients
      were in 1 of 4 previously recognised high risk groups. Of the 52% of patients not
      in a defined high risk category, 42% were otherwise healthy infants (>6 weeks of
      age) and 10% had chronic underlying illnesses generally not associated with an
      increased risk of severe RSV disease. Patients not in a defined high risk
      category accounted for 46% of total hospital days. CONCLUSION: In order to reduce
      overall RSV hospitalisation rates and the economic burden to society, programmes
      for disease prevention must be directed at healthy infants as well as children in
      recognised high risk categories. Even if all currently eligible candidates were
      to have received passive immunoprophylaxis, which yields about a 50% reduction in
      hospitalisation rates, the number of RSV hospitalisations in our 3-year study
      would have been reduced by no more than 9%. Without development and widespread
      use of an effective RSV vaccine, a major impact on RSV-induced hospitalisation is
      unlikely.

PMID- 10937465
TI  - Pneumocystis carinii pneumonia in adolescents.

PMID- 10937462
TI  - Recognising antibacterial hypersensitivity in children.
AB  - Adverse reactions to antibacterial agents are not uncommon in children. They are
      classified as 'immediate' or 'nonimmediate' according to the time interval
      between drug administration and onset. Immediate reactions occur within 1 hour
      and are manifested by urticaria and/or angioedema, bronchospasm and anaphylactic
      shock; immunological reactions are mediated by IgE antibodies. The main
      nonimmediate reactions (occuring after more than 1 hour) are maculopapular rash,
      urticaria and serum sickness; T lymphocytes may participate in maculopapular
      rash. Clinical assessment of such reactions is complex. The patient's history is
      fundamental; the allergological examination includes in vivo and in vitro tests
      selected on the basis of the clinical features and the phase of reaction. In the
      late phase, prick and intradermal tests are sensitive in evaluating beta-lactam
      allergy. Together with delayed-reading intradermal testing, patch testing seems
      to be useful in diagnosing maculopapular reactions to systemically administered
      aminopenicillins. Determination of specific IgE levels is the most common in
      vitro method for diagnosing immediate reactions. In the acute phase, serum
      tryptase and urinary N-methylhistamine assays are reliable in diagnosing type I
      pathogenic mechanisms in immediate reactions. Unfortunately, there are few in
      vitro tests for evaluating other reactions, and most are not fully validated. In
      selected cases, provocation tests should be performed.

PMID- 10937463
TI  - Anticonvulsants and breast feeding: a critical review.
AB  - Progress in the diagnosis and management of seizure disorders and the
      availability of effective anticonvulsive medications has enabled increasing
      numbers of epileptic women of child-bearing age to raise families. Breast
      feeding, which these women may wish to choose, provides health, nutritional,
      immunological, developmental, social, economic and environmental benefits. The
      traditional anticonvulsants, such as phenytoin, carbamazepine and valproic acid
      (valproate sodium), are generally considered safe for use during breast feeding;
      however, observation for adverse effects is recommended. The use of phenobarbital
      while breast feeding is controversial because of its slow elimination by the
      nursing infant. The newer anticonvulsants, such as clobazam, felbamate,
      gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, and vigabatrin,
      are used mainly as adjunctive therapy. Data on the use of these drugs in
      pregnancy and lactation, and regarding long term effects on cognition and
      behaviour, are sparse. Weighing the benefits of breast feeding against the
      potential risk to the nursing infant, breast feeding is considered to be safe
      when the mother is taking carbamazepine, valproic acid or phenytoin. Infant
      monitoring for potential adverse effects is advisable when the mother is taking
      phenobarbital, clobazam, gabapentin, lamotrigine, oxcarbazepine or vigabatrin.
      Monitoring of infant serum drug concentrations is advisable but not compulsory.
      The use of felbamate, tiagabine and topiramate during breast feeding should await
      further study.

PMID- 10937466
TI  - Diphtheria-tetanus-acellular pertussis vaccine adsorbed (Triacelluvax; DTaP3-CB):
      a review of its use in the prevention of Bordetella pertussis infection.
AB  - DTaP3-CB (Triacelluvax) is an acellular pertussis (aP) vaccine containing 3
      antigens from purified Bordetella pertussis bacteria combined with diphtheria and
      tetanus toxoids (DT). In addition to purified filamentous haemagglutinin and
      pertactin, DTaP3-CB contains pertussis toxin which has been genetically rather
      than chemically detoxified. As shown in randomised, double-blind clinical trials
      in infants, DTaP3-CB elicits an immune response similar to or greater than that
      of whole cell (DTwP) vaccines. Results of a large multicentre study comparing
      DTaP3-CB with 12 acellular and 1 DTwP vaccine indicate that DTaP3-CB, like all
      acellular vaccines, induces variable immune responses to different pertussis
      antigens; however, antibody titres to pertussis toxin are normally higher after
      immunisation with the genetically detoxified vaccine than with other 3- or 4
      component vaccines. When given as a fourth or fifth booster dose, DTaP3-CB
      produced a significant immune response in infants primed with 3 doses of either a
      DTaP or DTwP vaccine. Virtually all infants immunised with DTaP3-CB had a
      serological response to diphtheria and tetanus toxoids. Data from 2 very large
      efficacy studies indicate that DTaP3-CB has high and long lasting protective
      efficacy against culture-confirmed pertussis which is greater than that of a 2
      component vaccine (DTaP2-SB) and the whole cell DTwP-CON vaccine after a 3-, 5-
      and 12-month immunisation schedule and after a 2-, 4- and 6-month schedule with
      the DTwP-CON vaccine. However, the DTwP-CON whole cell vaccine has been noted for
      its low immunogenicity in 1 study and low efficacy and immunogenicity in another
      study. On the other hand, DTaP3-CB vaccine has similar efficacy to DTaP3-SB
      (after immunisation at 2, 4 and 6 months), DTaP5-CON and DTwP-EVANS against
      culture-confirmed pertussis with > or =21 days cough in infants immunised
      according to a 3-, 5- and 12-month schedule. Infants immunised with DTaP3-CB
      experienced significantly fewer adverse events such as pain, redness, swelling
      and irritability than infants given DTwP. DTaP3-CB has a similar tolerability
      profile to other acellular vaccines and is associated with similar rates of local
      tenderness, irritability, fever (> or =40 degrees C) and persistent crying.
      Comparative trials have shown that infants immunised with DTaP3-CB had a lower
      incidence of pain at the site of injection and fever (> or =38 degrees C)
      compared with other acellular vaccines, although this may have little clinical
      significance. Concomitant administration of DTaP3-CB with hepatitis B, oral polio
      or Haemophilus influenzae type B vaccines did not affect the immunogenicity of
      these other paediatric vaccines. CONCLUSION: Data from clinical trials with DTaP3
      CB vaccine indicate that this vaccine induces high and long lasting efficacy. It
      is at least as efficacious as most whole cell vaccines and generally similar in
      efficacy to the most efficacious acellular pertussis vaccines containing 3 or
      more pertussis antigens. DTaP3-CB is better tolerated than whole cell vaccines
      and has a similar tolerability profile to other acellular vaccines; the possible
      lower risk of severe adverse events remains to be confirmed. The low
      reactogenicity of DTaP3-CB is likely to make it well tolerated and therefore well
      accepted for the immunisation of infants, thereby enabling wider implementation
      of vaccination programmes.

PMID- 10937467
TI  - Juvenile myasthenia: diagnosis and treatment.
AB  - Myasthenia in children can be juvenile (autoimmune) or congenital. Juvenile
      myasthenia (JM) is an autoimmune disorder characterised by fluctuating weakness
      and fatigue in the ocular, facial, bulbar or limb muscles. Diagnosis is confirmed
      by electromyography (EMG), single fibre EMG and the patient's clinical response
      to anticholinesterase medication. Serology is less helpful in children because
      acetylcholine receptor antibodies, usually positive in adults, are frequently
      absent in patients with prepubertal onset of the disease. Treatment methods in JM
      include anticholinesterase drugs, thymectomy and immunomodulatory agents.
      Plasmapheresis and intravenous immunoglobulin are used in myasthenic crisis. The
      prognosis of patients with JM is usually good, clinical remission being achieved
      in the majority of patients with the current treatment methods.

PMID- 10937468
TI  - Supraventricular tachycardia in infants, children and adolescents: diagnosis, and
      pharmacological and interventional therapy.
AB  - Supraventricular tachycardia is the most frequent form of symptomatic
      tachydysrhythmia in children. Neonates and infants with paroxysmal
      supraventricular tachycardias generally present with signs of acute congestive
      heart failure. In school-aged children and adolescents, palpitations are the
      leading symptom. Chronic-permanent tachycardia results in a secondary form of
      dilated cardiomyopathy. Therapy for episodes of tachycardia depends on the
      individual situation. In severe haemodynamic compromise, or if ventricular
      tachycardia is suspected, tachycardia should immediately be terminated by
      external cardioversion during deep sedation. Vagal manoeuvres are effective in
      patients with atrioventricular reentrant tachycardias. Adenosine is the drug of
      first choice in any age group for tachycardias involving the atrioventricular
      node; its advantages include short half-life and minimal or absent negative
      inotropic effects. Adenosine may also be used in patients with wide QRS complex
      tachycardia. Intravenous verapamil is contraindicated in neonates and infants
      because of the high risk of electromechanical dissociation. In older children (>5
      years) and adolescents, verapamil may be administered with the same restrictions
      as in adult patients (wide QRS complex tachycardia, significant haemodynamic
      compromise). Spontaneous cessation of tachycardia can be expected in most
      neonates and infants during the first year of life. Prophylactic pharmacological
      treatment in this age group is advisable because recognition of tachycardia is
      often delayed until the occurrence of symptoms. Withdrawal of drug treatment
      should be attempted around the end of the first year. However, in older children,
      spontaneous cessation of tachycardia is rare. Prophylactic drug therapy is
      performed on an empirical basis. Digoxin may be administered in all forms of
      supraventricular tachycardia in which the atrioventricular node is involved,
      except in patients with pre-excitation syndrome aged >1 year. In patients with
      atrioventricular reentrant tachycardia, class IC drugs such as flecainide and
      propafenone are effective. Sotalol is also effective in atrioventricular
      reentrant tachycardia, as well as in primary atrial tachycardia. Although
      amiodarone has the highest antiarrhythmic potential, it should be used with
      caution because of its high rate of adverse effects. In school-aged children and
      adolescents, radiofrequency catheter ablation of the anatomical substrate is an
      attractive alternative to drug therapy, with a rate of permanent cessation of the
      tachycardia of up to 90%. Despite the clear advantages of this procedure, it
      should be performed only with unquestionable indication; the long term
      morphological and electrophysiological sequelae on the growing atrial and
      ventricular myocardium are still unknown.

PMID- 10937469
TI  - Antidepressants and breast-feeding: a review of the literature.
AB  - For every antidepressant so far investigated in the breast milk of mothers
      prescribed these medications, findings indicate that some amount of drug will be
      excreted into the breast milk. Nursing infants will be exposed to some, usually a
      very low, amount of drug and drug metabolites. Levels of drug exposure to infants
      for the many antidepressants available are examined, discussing milk to plasma
      drug concentration ratios and the infant dose as a percentage of the maternal
      dose. Drug concentrations in infant plasma and adverse effects of drug exposures
      to infants are reviewed. Factors influencing the decision on whether to breast or
      bottle feed an infant nursed by a mother taking antidepressants are discussed,
      concluding that the decision needs to be made on an individual basis. The
      lactating mother, in consultation with her doctor, should be in a position to
      make an informed decision on whether or not to breast feed. Under certain
      circumstances the decision to bottle feed may be wise, but more commonly the
      advantages of breast-feeding will outweigh the very low risk of an adverse event
      from drug exposure to the infant.

PMID- 10937470
TI  - Therapy of Crohn's disease in childhood.
AB  - Crohn's disease in childhood is a chronic relapsing condition with a high
      morbidity. Growth failure is common. The aim of therapy is to induce and then
      maintain disease remission and thereby promote well-being and normal growth and
      development. Enteral nutrition (either polymeric or elemental) is effective and
      used as initial therapy. This is employed as sole therapy over a 6- to 8-week
      period followed by a period of controlled food reintroduction. The relapse rate
      is high and further courses of enteral nutrition or alternative therapies are
      frequently required. Corticosteroids are also effective as initial therapy and
      are required in difficult cases but there are problems with their long term use,
      particularly their adverse effects on growth. Many patients develop either
      corticosteroid-dependent or corticosteroid-resistant disease. In this instance,
      additional immunosuppression, such as azathioprine, can be used. Surgery is
      required for those patients with disease resistant to medical therapy and this
      will result in remission; however, the relapse rate with surgery is high. There
      are many areas for future research. Very little is known about why enteral
      nutrition works, how long it should be given or its role as maintenance therapy.
      Newer immunosuppressive strategies based on cytokine modulation may be helpful in
      children once more experience is gained from their use in adults.

PMID- 10937471
TI  - Control of malabsorption in cystic fibrosis.
AB  - Intestinal malabsorption is severe and of early onset in virtually all people who
      have cystic fibrosis. The main cause is deficiency of pancreatic enzymes, but
      bicarbonate deficiency, abnormalities of bile salts, mucosal transport and
      motility, and anatomical structural changes are other contributory factors.
      Appropriate pancreatic replacement therapy will achieve normal or near normal
      absorption in many patients. It is important to identify both malabsorption and
      evidence of a pancreatic lesion in all patients who are to receive pancreatic
      enzymes. All who have evidence of fat malabsorption are deemed pancreatic
      insufficient and candidates for enzyme replacement therapy. Effective treatment
      should allow a normal diet to be taken, control symptoms, correct malabsorption
      and achieve a normal nutritional state and growth. The occurrence of fibrosing
      colonopathy in some patients receiving very high doses of those enzymes that have
      the copolymer Eudragit L30 D55 in their covering has resulted in guidelines in
      the UK to avoid dosages greater than the equivalent of 10,000 IU lipase/kg/day
      for all patients and also to avoid preparations containing this copolymer in
      children and adolescents. For patients not responding to 10,000 IU lipase/kg/day,
      review of adherence to treatment, change of enzyme preparation, variation of the
      time of administration and reduction in gastric acid may improve absorption. The
      importance of excluding other gastrointestinal disorders as a cause of the
      patient's symptoms and the need for early investigations, rather than merely
      increasing the dosage of enzymes, is stressed. With modern enzymes, adequate
      control of gastrointestinal symptoms and absorption can be achieved at dosages of
      10,000 IU lipase/kg/day or only slightly more, and a normal nutritional state and
      growth rate maintained in most patients with cystic fibrosis.

PMID- 10937472
TI  - Analgesics and breast-feeding: safety considerations.
AB  - The issue of prescription of analgesics during lactation is clinically important
      but also complex. Most of the information available is based on single dose or
      short term studies, and for many drugs only a single or a few case reports have
      been published. As great methodological problems exist in the assessment of
      possible adverse drug reactions in neonates and infants, there is limited
      knowledge about the practical impact of the, often very low, concentrations
      found. Nevertheless, some recommendations can be made. Breast-feeding during
      maternal treatment with paracetamol (acetaminophen) should be regarded as being
      safe. Short term use of nonsteroidal anti-inflammatory drugs seems to be
      compatible with breast-feeding. For long term treatment, short-acting agents
      without active metabolites, such as ibuprofen, should possibly be preferred. The
      use of aspirin (acetylsalicylic acid) in single doses should not pose any
      significant risks to the suckling infant. Use of codeine is probably compatible
      with breast-feeding, although the effects of long term exposure have not been
      fully elucidated. For propoxyphene, it seems unlikely that the suckling infant
      will ingest amounts that will cause any detrimental effects during short term
      treatment. However, it cannot be excluded that significant amounts of the
      metabolite norpropoxyphene may arise in the suckling infant during long term
      exposure. Treatment of the mother with single doses of morphine or pethidine
      (meperidine) is not expected to cause any risk for the suckling infant. Repeated
      administration of pethidine, in contrast to morphine, affects the suckling infant
      negatively. Thus, morphine should be preferred in lactating mothers. However,
      during long term treatment with morphine, the importance of uninterrupted breast
      feeding should be assessed on an individual basis against the potential risk of
      adverse drug effects in the infant. If it is decided to continue breast-feeding
      the infant should be observed for possible adverse effects. In general, if
      treatment of a lactating mother with an analgesic drug is considered necessary,
      the lowest effective maternal dose should be given. Moreover, infant exposure can
      be further reduced if breast-feeding is avoided at times of peak drug
      concentration in milk. As breast milk has considerable nutritional, immunological
      and other advantages over formula milk, the possible risks to the infant should
      always, and on an individual basis, be carefully weighed against the benefits of
      continuing breast-feeding.

PMID- 10937473
TI  - Medication errors in paediatrics: a case report and systematic review of risk
      factors.

PMID- 10937474
TI  - Why do we need a new journal in paediatric pharmacology?

PMID- 10937475
TI  - Drug treatment of migraine in children: a comparative review.
AB  - Migraine according to the criteria of the International Headache Society, occurs
      in about 3 to 7% of all children. Despite this high incidence, and unlike the
      situation with adult migraine, only a very few controlled trials have
      investigated the acute and prophylactic treatment of migraine in children. In the
      acute migraine attack, ibuprofen 10 mg/kg and paracetamol (acetaminophen) 15
      mg/kg have been shown to be effective, with only a few adverse effects. In severe
      migraine attacks, dihydroergotamine mesylate (dihydroergotamine) administered
      orally (20 to 40 microg/kg) or intravenously (maximum 1 mg/day) may be helpful,
      but there have been no large placebo-controlled trials of this treatment. Oral
      sumatriptan has not been effective in several double-blind and placebo-controlled
      trials; administered subcutaneously, this drug might be helpful but the only data
      for this application come from open trials. For migraine prophylaxis, only
      flunarizine 5 mg/day has been shown to be effective in more than 1 double-blind,
      placebo-controlled trial. Some evidence also exists that propranolol >60 mg/day
      and pizotifen 0.5 to 1.5 mg/day are effective; however, the results from
      different trials are contradictory. For all other drugs studied in migraine
      prophylaxis, the results remain vague (e.g. amitriptyline, nimodipine, trazodone)
      or suggest inefficacy (e.g. timolol, clonidine, tryptophan). In migraine-related
      disorders, pizotifen 0.5 to 0.75 mg/day for abdominal migraine and flunarizine 10
      to 25 mg/day for alternating hemiplegia have been shown to be effective. Most of
      the drugs used in the treatment of migraine in children are well tolerated and
      without relevant adverse effects. In migraine prophylaxis, the most common
      adverse effects are drowsiness and bodyweight gain.

PMID- 10937477
TI  - Management of acute otitis media in the 1990s: the decade of resistant
      pneumococcus.
AB  - Acute otitis media (AOM) has become increasingly difficult to treat in the 1990s,
      the decade of drug-resistant pneumococcus. Throughout the world, drug-resistant
      strains of this pathogen are being recovered from 20 to 50% of cases of initial
      untreated AOM, and from 45 to 90% of refractory AOM. Almost as alarming is that
      beta-lactamase-producing strains of Haemophilus influenzae are currently being
      isolated in 40 to 50% of cases of AOM in the US. Clinicians can no longer expect
      'Pollyanna-like' high rates of clinical resolution for this disease. It is now
      imperative that they become aware of the regional prevalence of these drug
      resistant bacteria and, just as importantly, their patterns of antibacterial
      resistance. Although some authors would hold that any antibacterial, or even
      placebo, should be adequate for most cases of AOM, clinical practice appears to
      suggest otherwise. Amoxicillin, still the first-line therapeutic choice for
      initial nonrefractory AOM, will often fail. The real dilemma begins when
      clinicians search for clinical data to select an antibacterial for therapeutic
      failures--few data are available. Thus, to give optimal treatment to a child who
      has failed antibacterial therapy--the true actual indication for all second-line
      antibacterials--they must instead become familiar with the following in vivo and
      in vitro data: 1. 'In vivo sensitivity data': otherwise known as bacteriological
      efficacy, in which repeat tympanocentesis is performed in mid-therapy. This
      reveals the bacterial 'Achilles heel' or weakness for the individual
      antibacterial agents. 2. Clinical efficacy data: analysis of rates of clinical
      resolution after therapy in comparative trials which use a single tympanocentesis
      initially and a 'gold standard' comparator antibacterial. 3. 'Bug to drug' data:
      comparison of reported middle ear concentrations for each individual
      antibacterial agent relative to the respective minimum inhibitory concentrations
      of isolates, particularly drug-resistant pneumococcus and H. influenzae (if
      possible, obtained from the paediatric respiratory tract). The selection of an
      antibacterial agent for AOM in any particular case should not be merely a random
      process. It involves awareness of the pathogens most likely to be observed: with
      co-infections; after failure with a particular antibacterial (the bacterial
      'Achilles heel' of the drug); and at different points in time, whether initially
      or after therapeutic failures (e.g. first-line versus fourth-line failure).

PMID- 10937476
TI  - Current perspectives on the drug treatment of neonatal respiratory distress
      syndrome.
AB  - Respiratory distress syndrome (RDS) in preterm neonates is caused by a lack of
      alveolar surfactant, which leads to decreased pulmonary compliance and increased
      work of breathing. Effective therapy for RDS has reduced mortality at the expense
      of increasing the number of preterm survivors with chronic lung disease. Drugs
      such as corticosteroids, proterelin (thyrotropin-releasing hormone) and ambroxol
      have all been administered to mothers to promote fetal lung maturation, but of
      these only corticosteroids have been proven to be of benefit. The management of
      RDS includes assisted ventilation and surfactant replacement therapy. There are
      several surfactant preparations, some synthetic and others derived from animal
      lungs, and recent research has been directed at finding which, if any, is
      superior. The timing of the first dose has also been studied. Prophylactic
      surfactant administration within the first 15 minutes of life appears to be more
      efficacious than later treatment for very preterm babies, but could lead to some
      neonates being treated unnecessarily and perhaps being exposed to adverse
      effects. Newer treatments for neonates with RDS are aimed at reducing the
      pulmonary inflammation that occurs as a result of ventilatory barotrauma and
      oxygen toxicity. Superoxide dismutase, along with other antioxidants, may be
      beneficial as a free radical scavenger to reduce oxygen toxicity. Inhaled nitric
      oxide may reduce oxygen requirements by reducing ventilation-perfusion
      mismatching, and early treatment with corticosteroids may reduce pulmonary
      inflammation. All of these treatments are currently undergoing clinical trials.

PMID- 10937478
TI  - Cetirizine: a review of its use in children with allergic disorders.

PMID- 10937480
TI  - The history of the acetone-butanol project in Austria.
AB  - The acetone-butanol fermentation and the closely related 2-propanol-butanol
      fermentation are of interest to Europe in particular for environmental and
      socioeconomic reasons, but its economic and technical feasibility must be proven
      before reestablishment as a commercial proposition. In particular the
      reestablishment of a new, fledgling fermentation industry selling into markets
      presently serviced by the mature, firmly established and highly capitalised
      petrochemical industry will require a significant driving force or else
      commercial users, who frequently have long-term supply contracts, will remain
      with known and proven suppliers. Hence the present state-of-the-art of the
      acetone-butanol fermentation is best described as technically and economically
      difficult but possible in niche markets. The most likely future is for decentral
      fermentation facilities processing locally made substrates and selling into niche
      markets.

PMID- 10937479
TI  - Applied acetone-butanol fermentation.

PMID- 10937481
TI  - Clostridial iron-sulphur proteins.
AB  - Iron-sulfur proteins are ubiquitous catalysts of a wide range of biological
      reactions, and are particularly abundant in clostridia which lack the ability to
      synthesize hemes. The development of research on these metalloproteins has
      therefore been strongly associated with biochemical investigations of clostridial
      metabolism. Major breakthroughs in the field, from the first isolation of an iron
      sulfur protein in 1962, to the recent determination of an Fe-hydrogenase
      structure, have been made with clostridia. These data, as well as others obtained
      through studies on clostridia, are transferable to many other bioenergetic
      machineries, due to the strong phylogenetic conservation of some important
      components. For instance, clear homologies exist between constituents of the
      anaerobic electron transfer chains in clostridia and aerobic respiratory chains.
      The contribution of iron-sulfur proteins to the biotechnological and medical
      significance of clostridia is also discussed. Structural and functional genomics
      are expected to bring forth a wealth of novel data on clostridia and iron-sulfur
      proteins.

PMID- 10937483
TI  - Bacteriophage infections in the industrial acetone butanol (AB) fermentation
      process.
AB  - The reported incidence and effects of bacteriophage infections occurring in the
      industrial acetone butanol (AB) fermentation processes operated in the USA,
      Japan, and Puerto Rico during the earlier part of the twentieth century is
      reviewed. The growth characteristics and solvent-producing ability of a lysogenic
      strain of Clostridium madisonii isolated from a phage infection in Puerto Rico
      was determined in molasses fermentation medium. The host strain harbours a large
      lysogenic phage belonging to the Siphoviridae and the growth rate of the
      lysogenic strain was found to be slower than the non-lysogenic parent strain and
      exhibited reduced solvent production. The history of phage infections that
      occurred in the South African AB process is documented along with the various
      remedial actions that were taken to restore production. A more detailed account
      of the last phage infection that occurred in 1980 involving a small pseudo
      lysogenic phage belonging to the Podoviridae is given. This phage infected
      Clostridium beijerinckii P260 and a number of closely related industrial strains.
      Factory-scale fermentations contaminated by this phage were compared with
      equivalent laboratory-scale control fermentations. The effect of the phage
      infection in the full-scale and laboratory-scale fermentations were monitored.
      Results obtained in laboratory-based studies included an assessment of the effect
      of the multiplicity of infection and the timing of phage infection. The general
      effects and symptoms of phage infections in the industrial AB fermentation are
      reviewed including gross changes in the fermentation and changes in cell
      morphology. Common techniques used for the diagnosis of phage infections and
      approaches for controlling phage contamination in the AB fermentation are
      discussed. Prevention strategies included good factory hygiene, sterilisation,
      decontamination and disinfection, and the use of resistant strains immunised
      against specific phages.

PMID- 10937482
TI  - The acetone-butanol fermentation in pilot plant and pre-industrial scale.
AB  - A summary of literature data concerning pilot or preindustrial scale trials of
      the acetone-butanol fermentation throughout its history is given. The recent
      pilot plant trials in Austria are also described for the first time. Some aspects
      of the current development of the acetone-butanol fermentation in general,
      especially from a technical point of view are also discussed.

PMID- 10937484
TI  - The economics of acetone-butanol fermentation: theoretical and market
      considerations.
AB  - Acetone-butanol (AB) fermentation was once run commercially in many countries
      until these chemicals could be made more cheaply from fossil oil sources.
      Research into the revitalisation of the process has shown that the process could
      once again be run economically in niche markets if run in a relatively small
      industrial scale processing low-grade agricultural products. The following
      analysis is intended to help identify suitable niche markets.

PMID- 10937485
TI  - Identification and characterization of a second butyrate kinase from Clostridium
      acetobutylicum ATCC 824.
AB  - A gene encoding a new butyrate kinase isozyme (BKII) was identified from the C.
      acetobutylicum ATCC 824 DNA database. The enzyme was expressed in Escherichia
      coli, purified, and characterized. The purified enzyme exhibited a subunit
      molecular mass of 43 kDa by SDS-PAGE, and a native molecular mass of 80 kDa by
      gel filtration suggesting it functions as a dimer. In the butyryl phosphate
      forming direction the optimal pH of BKII was 8.5. The enzyme had a Km of 0.62 M
      and a turn over rate of 2.2 x 10(5)/sec (Vmax of 165 units/mg). The presence of a
      mRNA encoding the BKII was demonstrated using a reverse transcription PCR
      reaction. The expression of the BKII in Clostridium acetobutylicum ATCC 824 was
      further examined by Western blot analysis using a polyclonal antibody prepared
      against recombinant BKII.

PMID- 10937486
TI  - Acetone, butanol and ethanol production from domestic organic waste by
      solventogenic clostridia.
AB  - Domestic organic waste (DOW) was washed and dried to 85 % dryness by VAM (The
      Netherlands). This material contained 25.1 g glucose, 8.4 g xylose and 5.8 g
      other monosaccharides/100 g dry matter. Using Mansonite steam explosion and
      enzymatic hydrolysis, a hydrolysate containing 15.4 g glucose, 2.2 g xylose and
      0.8 g other monosaccharides per l was made. Clostridium acetobutylicum DSM 1731
      produced 1.5 and C. beijerinckii B-592 0.9 g/l ABE and Clostridium LMD 84.48 1.9
      g/l IBE, respectively, from this hydrolysate without further supplementation.
      Incubation with 2 fold concentrated hydrolysate completely impaired ABE
      production. After removal of unspecific inhibiting components, the yield of ABE
      production by Clostridium acetobutylicum DSM 1731 increased about 3 fold as
      compared to the nontreated hydrolysate. From 4 fold concentrated, partially
      purified, hydrolysate containing 34.2 g glucose/l, ABE production was 9.3 g/l
      after 120 h as compared to 3.2 g ABE/I from non-concentrated hydrolysate which
      contained 12.0 g glucose/l after elution over the same column. The concentration
      of butyric acid in the fermented hydrolysates was 2.2 and 0.4 g/l, respectively.
      This reasonably low amount of butyric acid showed that the fermentation had
      proceeded quite well.

PMID- 10937487
TI  - KdpE of Clostridium acetobutylicum is a highly specific response regulator
      controlling only the expression of the kdp operon.
AB  - KdpE from Clostridium acetobutylicum was enriched in form of its Strep-tag
      derivative to allow easy immunodetection. It could be artificially phosphorylated
      by acetyl phosphate or carbamyl phosphate. Only phosphorylated clostridial KdpE
      was able to bind to a region upstream of the clostridial kdp structural genes.
      The minimal sequence requirements for binding were determined and found to share
      significant similarity with the Escherichia coli KdpE binding motif. However, the
      clostridial protein proved to be much more specific and did not bind in
      unphosphorylated form or to other similar sequences either from C. acetobutylicum
      or E. coli. In contrast, the enterobacterial protein recognized the clostridial
      binding motif. An HPt domain has been detected in KdpD from C. acetobutylicum,
      the cognate sensor kinase of KdpE. The data reported indicate that in E. coli,
      KdpE might represent a regulatory checkpoint for different phosphorelay
      signalling pathways, whereas in C. acetobutylicum KdpD might serve this function.

PMID- 10937488
TI  - Construction of a reporter gene vector for Clostridium beijerinckii using a
      Clostridium endoglucanase gene.
AB  - A beta-1,4-endoglucanase gene (eglA) cloned from C. acetobutylicum P262 was
      selected for use in the development of a reporter system for C. beijerinckii
      NCIMB 8052. The reporter plasmid, pER1, was constructed by ligating the
      promoterless eglA gene into the B subtilis/Clostridium shuttle vector, pFNK1,
      which can replicate and is stably maintained in C. beijerinckii. The expression
      of the endoglucanase enzyme from its own promoter was not significantly induced
      in cells grown in glucose, sucrose or galactose, while growth of cells in
      cellobiose or fructose resulted in lower levels of activity. The enzyme was
      efficiently secreted into the culture medium and did not remain associated with
      the cell in any way. A transcriptional fusion between the glutamine synthetase
      (glnA) promoter region and the promoterless eglA gene resulted in high levels of
      endoglucanase expression, which reflected an 11-fold increase in expression
      levels over the eglA promoter.

PMID- 10937489
TI  - Development of a transformation and gene reporter system for group II, non
      proteolytic Clostridium botulinum type B strains.
AB  - Non-proteolytic, Group II strains of Clostridium botulinum are of particular
      concern to the food industry because of their ability to survive and grow in
      REPFEDs (refrigerated processed foods of extended durability). Their analysis
      would benefit from the availability of a gene transfer system. In the present
      study we have been able, for the first time, to demonstrate transformation in a
      representative Group II strain, ATCC 25765. Initial attempts to transform ATCC
      25765 with existing clostridial cloning vectors (pMTL540E and pMTL500E) were,
      however, prevented by a restriction barrier. Through a combination of classical
      and molecular approaches we were able to show that strain ATCC 25765 possesses a
      restriction endonuclease (Cbol) and a methylase activity (M. Cbol) which have the
      same specificity as Mspl and M.Mspl, respectively. Cbol cleaves the palindrome 5'
      CCGG-3' to generate a 3'-GC sticky end, whilst M.Cbol specifically methylates the
      external C residue. An E. coli host was generated which expressed a Bacillus
      subtilis methylase enzyme (M.BsuF1) with equivalent specificity to M.Cbol.
      Plasmids (pMTL540E and pMTL500E) prepared in this strain were subsequently shown
      to be capable of transforming ATCC 25765. The highest frequencies (0.8 X 10(4)
      transformants per microg of DNA) were obtained when cells were cultivated in
      media supplemented with 1% (w/v) glycine, and when the electroporation was
      undertaken at 10 kV/cm, 25 microF and at 400 ohms. Having developed an effective
      transformation procedure, we went on to construct reporter cassettes based on the
      Thermanaerobacterium sulfurigenes lacZ and the Vibrio fischeri luxAB genes. Using
      the former, and promoter regions isolated from the botulinum toxin genes, we have
      obtained preliminary evidence that reporter genes may be used to evaluate the
      physiological factors that affect toxin production in the food environment.

PMID- 10937490
TI  - Analysis of a catabolic operon for sucrose transport and metabolism in
      Clostridium acetobutylicum ATCC 824.
AB  - The utilization of sucrose by Clostridium acetobutylicum ATCC 824 was
      investigated. Sucrose was found to be transported via a phosphoenol-pyruvate
      (PEP)-dependent phosphotransferase system (PTS) and a metabolic pathway identical
      to that previously identified in C. beijerinckii, was established. The genes
      encoding the proteins of this pathway were identified from the C. acetobutylicum
      genome sequence, in the order scrAKB encoding Enzyme II of the sucrose PTS,
      fructokinase and sucrose 6-phosphate hydrolase respectively. While the pathway
      for sucrose metabolism is conserved between C. acetobutylicum and C.
      beijerinckii, the operons show considerable differences in organization and
      regulatory elements. The C. acetobutylicum scr operon contains the elements of an
      antiterminator-mediated regulation mechanism, typical of the BgIG family of
      regulators. The scrT gene, located upstream of scrA encodes an antiterminator
      that is preceded by a transcription terminator, which is overlapped by a
      classical ribonucleic antiterminator (RAT) sequence. We also propose the
      existence of a new variant RAT-like sequence which overlaps a terminator between
      scrT and the downstream structural genes.

PMID- 10937491
TI  - Conversion of solvent evaporation residues from the AB- (acetone - butanol)
      bioprocess into bacterial cells accumulating thermoplastic polyesters.
AB  - In a bioconversion study based on utilisation of by-products from the AB-
      (acetone - butanol) bioprocess a new isolated gram-negative solvent tolerant
      bacterium was used to convert the AB process residue after removal of the major
      part of the solvents. The bacterium identified as a representative of the genus
      Alcaligenes (designated as Alcaligenes sp. G) was capable of growth up to optical
      densities ranging from 8 to 20 and simultaneously of polyhydroxyalkanoate-(PHA
      )accumulation up to 40% per dry weight. A standardised medium based on AB by
      products containing 7 g/l of butyrate and 5 g/l of acetate at pH 7.5 was used in
      our studies for bioconversion into PHAs. Concentrations of 1-butanol, which is
      known for its membrane damaging properties in microorganisms, were tolerated in
      the AB by-products medium up to 4 g/l without significant inhibition of cellular
      growth. No inhibition of growth was observed, when the medium was adjusted to 40
      g/l butyrate. Due to the toxicity of the remaining 1-butanol maintenance of
      sterility is of no high priority during the process. The use of acetate and
      butyrate from an AB process is expected to provide a higher return-on-investment
      than the combustion of biogas to help meet energy demands.

PMID- 10937492
TI  - Butanol tolerance of Clostridium beijerinckii NCIMB 8052 associated with down
      regulation of gldA by antisense RNA.
AB  - Strain BR54 of Clostridium beijerinckii was derived from the wild type strain,
      NCIMB 8052, by mutagenesis with Tn1545 and selection for butanol tolerance. It
      harbours a single copy of Tn 1545 in a 435 bp intergenic region separating two
      convergently transcribed genes, accC and gldA. The former encodes biotin
      carboxylase (E.C.6.3.4.14), a subunit of acetyl-CoA carboxylase and the latter
      encodes glycerol dehydrogenase (E.C.1.1.1.6). Since Tn1545 generates outwardly
      directed transcripts from its right end, we considered the possibility that the
      transposon inserted in strain BR54 might affect the expression of the adjacent
      gldA gene. RT-PCR experiments revealed that the mutant, but not the wild type,
      contains antisense RNA corresponding to the gldA gene. Correlated with this, the
      level of glycerol dehydrogenase activity in the mutant was only 25% of that in
      the wild type when bacteria were grown with either glucose or glycerol as the
      fermentable substrate. We conclude that transcripts emerging from the right end
      of the conjugative transposon, Tn1545, can reduce the expression of the adjacent
      gldA gene by the generation of antisense RNA and that this is associated with a
      butanol-tolerant phenotype.

PMID- 10937493
TI  - The cause of "acid-crash" and "acidogenic fermentations" during the batch acetone
      butanol-ethanol (ABE-) fermentation process.
AB  - Experiments were performed to determine the cause of "acid crash", a phenomenon
      which occasionally occurs in pH-uncontrolled batch fermentations resulting in
      premature cessation of ABE (acetone butanol) production. The results indicate
      that "acid crash" occurs when the concentration of undissociated acids in the
      broth exceeds 57 - 60 mmol/l. Prevention can be achieved by introducing some
      limited pH control to minimize the concentration of undissociated acids or by
      slowing the metabolic rate, and thus the rate of acid production, by, for
      example, lowering the fermentation temperature. "Acidogenic fermentations", which
      occur when batch fermentations are performed at pH values close to neutrality,
      are due to rapid production of acids followed by inhibition of solventogenesis
      when the total acid concentration reaches 240 - 250 mmol/l. Solventogenesis can
      be achieved at these pH values by lowering the glucose uptake rate / acid
      production rate by use of e.g. elevated glucose or lowered yeast extract
      concentrations in the growth medium.

PMID- 10937494
TI  - Continuous two-stage ABE-fermentation using Clostridium beijerinckii NRRL B592
      operating with a growth rate in the first stage vessel close to its maximal
      value.
AB  - A two-stage continuous cultivation experiment with Clostridium beijerinckii NRRL
      B592 is described. The experiment was designed to mimic the two phases of batch
      culture growth of the organism in a two-stage continuous process. Thus in the
      first stage turbidostat the organism was grown acidogenically as rapidly as
      possible, and transferred to the second stage at the 'acid break point'. The
      second stage was designed to mimic the solventogenesis of the batch culture when
      it enters late exponential/early stationary phase. The volume of the second stage
      vessel was calculated to provide the necessary residence time for complete sugar
      utilization. It was hoped that the experimental set-up chosen would show whether
      data obtained from batch fermentation could be transferred directly to continuous
      culture. The culture maintained its ability to produce acetone, 1-butanol and
      ethanol at a dilution rate of 0.12 h(-1) for the first stage and 2.2 x 10(-2) h(
      1) for the second stage and achieved an average overall solvent concentration of
      15 g/l and an overall solvent productivity of 0.27 g/l/h for a period of steady
      state operation of more than 1600 hours. The productivity of solventogenesis in
      the first stage was dependent on the value of the growth rate of the culture
      which was in turn determined in part by the organism employed but also by the
      medium composition.

PMID- 10937495
TI  - A new insertion sequence, ISCb1, from Clostridium beijernickii NCIMB 8052.
AB  - The NCIMB 8052 strain of Clostridium beijerinckii contains nine copies of a novel
      insertion sequence, ISCb1, belonging to the IS4 family. The 1764 bp element has
      18 bp inverted repeats at its extremities, and generates 11 bp target repeats
      upon insertion. It contains a 1365 bp ORF whose predicted product (455 amino
      acids) resembles bacterial transposases. The highly conserved DD(35)E motif is
      present, as are signatures characteristic of the N3 and C1 domains of bacterial
      transposases. Codon usage of the ORF is somewhat different from that of other C.
      beijerinckii genes, suggesting that ISCb1 may have been acquired from another
      organism by horizontal gene transfer in the evolutionary past. One ISCb1 copy
      lies close to the site of insertion of Tn 1545 in a mutant strain, C10, which
      shows a reduced tendency to degenerate (i.e. loss of the potential to form
      solvents) compared with the wild type. In the C10 strain, the characteristic
      pattern of DNA fragments detected by an IS-specific probe was altered, but this
      was due to the Tn1545 insertion itself, rather than an ISCb1-mediated genome re
      arrangement. There is currently no evidence that the element is involved in
      strain degeneration, since 12 independently isolated spontaneous mutants that had
      lost the ability to form solvents had the same ISCb1 profile as that of the wild
      type strain. The element is apparently restricted to a series of closely related
      solvent-forming clostridia.

PMID- 10937496
TI  - Comparative fermentation studies of industrial strains belonging to four species
      of solvent-producing clostridia.
AB  - Industrial and culture collection strains of solvent-producing clostridia,
      classified as Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium
      saccharobutylicum, and Clostridium saccharoperbutylacetonicum were utilised in a
      comparative study of fermentation performance in a laboratory fermentation
      medium, a molasses fermentation medium, and a maize fermentation medium under
      standardised culture conditions. At least one representative strain was selected
      from each of the sub-groups within the four species. Preliminary evaluations were
      first undertaken for the three different fermentation media to determine the most
      appropriate media formulations, carbohydrate concentrations, and culture
      conditions for comparison of the solvent-producing ability of these strains.
      Standardised fermentation media and culture conditions were then selected for
      each of the comparative fermentation studies. These included TYA medium
      containing 4% glucose, a supplemented molasses medium containing 6% fermentable
      sugars, and a supplemented maize mash medium containing 8% maize. Additional
      comparative fermentation studies on industrial strains belonging to two species
      of solvent-producing clostridia were carried out in molasses containing higher
      concentrations of fermentable sugars, and the sugar concentrations supporting
      maximum levels of solvent production were determined. Although all the strains
      tested grew in the maize fermentation medium and degraded starch, only a few
      strains produced consistently high solvent levels. Optimum starch utilisation and
      solvent production was obtained at a maize concentration of 80 g/l. Pretreatment
      of the maize by milling or saccharification decreased the buffering capacity of
      the medium and resulted in decreased solvent production. Decreasing the time used
      to gelatinise the starch had little effect. Solvent yields and concentrations
      obtained in this study were compared with various published data in the
      scientific and patent literature and appeared to closely simulate the results
      obtained in the industrial fermentation process. The fermentation performances of
      individual strains could provide useful comparative data for the selection and
      development of strains for use on various commercial fermentation substrates.

PMID- 10937497
TI  - Diabetes-related autoantibodies and the selection of subjects for trials of
      therapies to preserve pancreatic beta-cell function in recent-onset type 1
      diabetes.

PMID- 10937498
TI  - Adaptation of cognitive function to hypoglycemia in healthy men.
AB  - OBJECTIVE: Antecedent hypoglycemia reduces hypoglycemic counterregulation and
      symptoms, thereby provoking the hypoglycemia unawareness syndrome. The effects of
      antecedent hypoglycemia on hypoglycemia-induced cognitive dysfunction are less
      well established. RESEARCH DESIGN AND METHODS: To determine whether antecedent
      hypoglycemia also reduces hypoglycemic cognitive dysfunction, we performed
      stepwise hypoglycemic clamp experiments (4.1, 3.6, 3.1, and 2.6 mmol/l) during a
      6-h period in 30 young healthy men. A total of 15 subjects additionally received
      a 2.5-h antecedent hypoglycemic clamp (3.1 mmol/l) on the preceding day (prior
      hypo group), whereas the other 15 subjects did not (control group). Cognitive
      function was assessed by auditory-evoked brain potentials (AEBPs) and reaction
      time during a vigilance task and short-term memory recall. Tests were performed
      during the stepwise hypoglycemic clamp at baseline and at each hypoglycemic
      plateau. RESULTS: In both groups, performance on all measures of cognitive
      function deteriorated during stepwise hypoglycemia (all P < 0.01). However, after
      antecedent hypoglycemia, the hypoglycemia-induced decrease in the amplitude of
      the P3 of the AEBP was distinctly reduced compared with the control condition (P
      < 0.05). Also, short-term memory performance was less impaired in the prior-hypo
      group than in the control group (P < 0.005), and a minor hypoglycemic impairment
      of reaction time (P < 0.05) was evident in the prior-hypo group. CONCLUSIONS:
      Data provide evidence that a single episode of mild antecedent hypoglycemia (3.1
      mmol/l) attenuates several aspects of cognitive dysfunction during subsequent
      hypoglycemia 18-24 h later.

PMID- 10937499
TI  - Efficacy of troglitazone on body fat distribution in type 2 diabetes.
AB  - OBJECTIVE: The insulin-sensitizing action of troglitazone may be mediated through
      the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma)
      and the promotion of preadipocyte differentiation in adipose tissue on which
      troglitazone has depot-specific effects. We investigated the relationship between
      efficacy of the drug and body fat distribution. Changes in body fat distribution
      were also investigated by long-term administration of the drug. RESEARCH DESIGN
      AND METHODS: Troglitazone was given at a dose of 400 mg/day to 20 patients with
      type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory
      glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found
      to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid
      levels, and body weight were measured monthly Body fat distribution was evaluated
      in subcutaneous (SC) and visceral fat using a computed tomography scan at
      umbilical levels before and after troglitazone therapy RESULTS: During the 1-year
      troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to
      7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight
      was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01).
      Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was
      significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients
      (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than
      in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c)
      during treatment showed a significant negative correlation with SC fat area (r = 
      0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone
      treatment resulted in increased accumulation of SC fat without a change in
      visceral fat area and, consequently. in a significant decrease in the visceral-to
      SC fat ratio. CONCLUSIONS: Predominant accumulation of SC fat for the visceral
      fat tissue was an important predictor of the efficacy of troglitazone therapy in
      patients with type 2 diabetes. Greater efficacy of troglitazone was observed in
      women who were characterized by more accumulation of SC adipose tissue than men.
      Long-term administration of the drug resulted in weight gain with increased
      accumulation of SC adipose tissue, probably because of the activation of PPAR
      gamma in the region.

PMID- 10937500
TI  - Use of an islet cell antibody assay to identify type 1 diabetic patients with
      rapid decrease in C-peptide levels after clinical onset. Belgian Diabetes
      Registry.
AB  - OBJECTIVE: To investigate whether the presence of antibody markers at diagnosis
      could help predict the rapid decrease in residual beta-cell function noted in
      some, but not all, patients with recent-onset type 1 diabetes. RESEARCH DESIGN
      AND METHODS: We measured random C-peptide levels (radioimmunoassay); islet cell
      cytoplasmic antibodies (ICA) (indirect immunofluorescence); and antibodies
      against IA-2 protein, 65-kDa glutamate decarboxylase, and insulin (liquid-phase
      radiobinding assays) in 172 patients <40 years of age with type 1 diabetes. The
      patients had been consecutively recruited at diagnosis by the Belgian Diabetes
      Registry and were followed for 2 years. RESULTS: Two years after diagnosis,
      random C-peptide levels had decreased significantly (P < 0.001) in ICA+ patients
      but not in ICA- patients. C-peptide values <50 pmol/ were noted in 88% of
      patients diagnosed before 7 years of age, in 45% of patients diagnosed between
      ages 7 and 15 years, and in 29% of patients diagnosed after 15 years of age (P <
      0.001). In cases of clinical onset before age 15 years, a rapid decline in random
      C-peptide values was observed almost exclusively in patients with high-titer ICA
      (> or =50 Juvenile Diabetes Foundation [JDF] units) at diagnosis (69 vs. 17% in
      patients with lower ICA titers, P < 0.001). In patients diagnosed after 15 years
      of age, 36% of patients with ICA titers > or =12JDF units developed low C-peptide
      levels compared with 14% of patients with ICA titers < 12 JDF units (P < 0.03).
      Multivariate analysis confirmed that C-peptide levels after 2 years were
      inversely correlated with ICA levels (P < 0.001) and to a lesser degree
      positively correlated with age at diagnosis (P < 0.02), regardless of the levels
      or number of molecular autoantibodies. CONCLUSIONS: Young age at diagnosis and
      high-titer ICA identify a group of type 1 diabetic patients at high risk of
      rapidly losing residual beta-cell function. Using these selection criteria, it is
      possible to better target beta-cell-preserving interventions to patients with or
      without such rapid progression, depending on the nature of the tested substance.
      The ICA assay measures clinically relevant antibodies not detected in antibody
      assays that use recombinant human autoantigens for substrate.

PMID- 10937501
TI  - Study of the Trp64Arg polymorphism of the beta3-adrenergic receptor in Greek
      women with gestational diabetes.
AB  - OBJECTIVE: This study assessed whether the Trp(64)Arg polymorphism of the beta3
      adrenergic receptor (beta3-AR), which has been associated with obesity, insulin
      resistance, weight gain, and earlier onset of type 2 diabetes, is more frequent
      in women who develop gestational diabetes mellitus (GDM) or whether it is
      associated with weight gain during pregnancy RESEARCH DESIGN AND METHODS: A total
      of 311 Greek pregnant women (180 with GDM and 131 without GDM [control]) who
      underwent a 100-g oral glucose tolerance test (OGTT) in the third trimester of
      pregnancy were genotyped for the beta3-AR Arg(64) polymorphism. Insulin levels
      were also determined during the OGTT. RESULTS: The frequency of Trp(64)Arg
      heterozygotes in this population was approximately 7% and was similar in the GDM
      and control groups (6.7 vs. 6.9%) as well as in the obese (BMI > or =27 kg/m2)
      and the nonobese (6.3 vs. 6.8%) subgroups. In the GDM group, BMI, fasting insulin
      resistance index, and diastolic blood pressure were significantly higher in
      Trp(64)Arg carriers; these differences were no longer observed when obesity was
      considered. In the 4 subgroups (control Trp(64)Trp and Trp(64)Arg and GDM
      Trp(64)Trp and Trp(64)Arg), a highly significant trend was evident of an increase
      in the percentage of subjects with shorter height. CONCLUSIONS: The frequency of
      the Arg(64) allele in Greek pregnant women is relatively rare compared with other
      ethnic groups and is probably not related to the development of GDM or obesity
      The observed tendency for shorter body height in Arg(64) carriers merits further
      evaluation in larger population samples.

PMID- 10937502
TI  - Effect of pregnancy on microvascular complications in the diabetes control and
      complications trial. The Diabetes Control and Complications Trial Research Group.
AB  - OBJECTIVE: To assess the effect of pregnancy on the development and progression
      of retinopathy and microalbuminuria in type 1 diabetes. RESEARCH DESIGN AND
      METHODS: We conducted longitudinal analyses of the Diabetes Control and
      Complications Trial (DCCT), a multicenter controlled clinical trial that compared
      intensive treatment with conventional diabetes therapy and studied 180 women who
      had 270 pregnancies and 500 women who did not become pregnant during an average
      of 6.5 years of follow-up. Women assigned to the conventional treatment group
      were changed to intensive therapy if they were planning pregnancy or as soon as
      possible after conception. Fundus photography was performed every 6 months, and
      the urinary albumin excretion rate (AER) was measured annually. RESULTS: Compared
      with nonpregnant women, pregnant women had a 1.63-fold greater risk of any
      worsening of retinopathy from before to during pregnancy (P < 0.05) in the
      intensive treatment group; the risk was 2.48-fold greater for pregnant vs. not
      pregnant women in the conventional group (P < 0.001). In the conventional group,
      the odds of > or =3-step progression from the baseline retinopathy level was >2.9
      fold among pregnant vs. not pregnant women (P = 0.003). The odds ratio (OR)
      peaked during the second trimester (OR = 4.26, P = 0.001) and persisted as long
      as 12 months postpregnancy (OR = 2.87, P = 0.005). The level of AER during
      pregnancy in the intensive group, but not in the conventional group, was
      significantly elevated from the level at baseline, albeit in the normal range.
      Although individual patients had transient worsening of retinopathy during
      pregnancy, even to the proliferative level, at the end of the DCCT, mean levels
      of retinopathy and albuminuria in subjects who had become pregnant were similar
      to those in subjects who had not become pregnant within each treatment group.
      CONCLUSIONS: Pregnancy in type 1 diabetes induces a transient increase in the
      risk of retinopathy; increased ophthalmologic surveillance is needed during
      pregnancy and the first year postpartum. The long-term risk of progression of
      early retinopathy and albumin excretion, however, does not appear to be increased
      by pregnancy.

PMID- 10937503
TI  - Prevalence of diabetes estimated by plasma glucose criteria combined with
      standardized measurement of HbA1c among health checkup participants on Miyako
      Island, Japan.
AB  - OBJECTIVE: To estimate the prevalence of diabetes in participants of an annual
      health checkup in the district of the Miyako Public Health Center (Okinawa,
      Japan) by using the revised criteria of the Japan Diabetes Society (JDS).
      RESEARCH DESIGN AND METHODS: The subjects studied here were all Japanese and 45
      75 years of age at the time of the health examination in 1998. Diagnosis of
      diabetes was based on the following: 1) fasting plasma glucose > or =7.0 mmol/l,
      2) casual plasma glucose > or =11.1 mmol/l, 3) HbA(1c) > or =6.1%, and 4) self
      report on a special questionnaire given at the examination. The HbA(1c) value was
      standardized by the measurement of 2 standard samples provided by the JDS.
      RESULTS: Among the 2,621 subjects, 59.7% had their fasting blood glucose levels
      measured. Of the subjects diagnosed as having diabetes, 154 (12.6%) were men and
      115 (8.6%) women. Among the subjects newly diagnosed with diabetes from their
      fasting blood glucose levels. 27.5% of the men and 21.9% of the women had
      diagnoses based on HbA(1c) alone. Overall, 34.9% of the subjects with newly
      diagnosed diabetes were identified by plasma glucose (PG) alone and 33.0% were
      diagnosed by HbA(1c) alone. CONCLUSIONS: The combination of PG and HbA(1c)
      resulted in a considerable increase in newly diagnosed diabetes as compared with
      the use of only one of these parameters. Considering the convenience and
      correlation with vascular complications, use of the 2 tests may be beneficial in
      epidemiological studies of the Japanese population to identify high-risk groups
      for micro- and macrovascular diseases.

PMID- 10937504
TI  - Plasma insulin and all-cause, cardiovascular, and noncardiovascular mortality:
      the 22-year follow-up results of the Helsinki Policemen Study.
AB  - OBJECTIVE: To investigate the association of plasma insulin with all-cause,
      cardiovascular, and noncardiovascular mortality. RESEARCH DESIGN AND METHODS: We
      studied 22-year mortality data from the Helsinki Policemen Study The study
      population comprised 970 men, 34-64 years of age, who were free of coronary heart
      disease, other cardiovascular disease, and diabetes. Area under the insulin
      response curve (AUC insulin) during an oral glucose tolerance test was used to
      reflect plasma insulin levels. RESULTS: During the follow-up period, 276 men
      died: 130 from cardiovascular and 146 from noncardiovascular causes. The hazard
      ratio (HR) for hyperinsulinemia (highest AUC insulin quintile vs. combined lower
      quintiles) with regard to all-cause mortality adjusting for age, was 1.94 (95% CI
      1.20-3.13) during the first 10 years of the follow-up period and 1.51 (1.15-1.97)
      during the entire 22 years; adjusting for other risk factors, the HR was 1.88
      (1.08-3.30) and 1.37 (1.00-1.87) during 10 and 22 years, respectively The
      corresponding HRs for cardiovascular mortality during 10 and 22 years were 2.67
      (1.35-5.29) and 1.73 (1.19-2.53), respectively, for age-adjusted and 2.30 (1.03
      5.12) and 1.39 (0.90-2.15), respectively, for multiple-adjusted HRs. A U-shaped
      association was observed between insulin and noncardiovascular mortality,
      multiple-adjusted HRs for lowest and highest versus middle AUC insulin quintiles
      were 1.85 (1.20-2.86) and 1.43 (0.91-2.24), respectively CONCLUSIONS:
      Hyperinsulinemia was associated with increased all-cause and cardiovascular
      mortality in Helsinki policemen independent of other risk factors, although these
      associations weakened with the lengthening of the follow-up period. The
      association of insulin with noncardiovascular mortality was U-shaped.

PMID- 10937505
TI  - Relationship between diabetes and mortality: a population study using record
      linkage.
AB  - OBJECTIVE: To determine patterns and causes of mortality for patients with
      diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study
      used cross-sectional record linkage, combining an electronic death register with
      a diabetic patient register constructed from a variety of routine health data
      sources collected from 1991 to 1997. The study was conducted in Cardiff and the
      Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and
      1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%)
      had diabetes recorded as an immediate or antecedent cause of death. Mortality
      rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the
      nondiabetic population. The standard mean ratio for the diabetic population was
      1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic
      population decreasing with age. Males with diabetes lost an average of 7.0 years
      from the year of diagnosis, and females with diabetes lost an average of 7.5
      years. The most common cause of death was cardiovascular disease, which accounted
      for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded
      as a cause of death on a minority of death certificates for patients with
      diabetes. Using death certificates in isolation, therefore, is a poor method of
      estimating diabetic mortality, but results can be improved with the use of record
      linkage techniques. Patients with diabetes have an excess risk of mortality
      compared with the nondiabetic population. Life-years lost for patients with
      diabetes is strongly related to age at diagnosis and is a means of expressing
      mortality without relying on accurate prevalence data.

PMID- 10937506
TI  - The 1997 American Diabetes Association and 1999 World Health Organization
      criteria for hyperglycemia in the diagnosis and prediction of diabetes.
AB  - OBJECTIVE: The 1997 American Diabetes Association (ADA) and the 1985 and 1999
      World Health Organization (WHO) criteria for diabetes and hyperglycemia differ.
      The appropriateness of these diagnostic criteria in terms of individuals
      identified as abnormal and their prognosis has been debated. The purpose of this
      study is to compare the classifications of people by these criteria and to
      compare fasting and postload plasma glucose concentrations in the prediction of
      diabetes. RESEARCH DESIGN AND METHODS: The frequencies of diabetes by the 3 sets
      of criteria were compared in 5,023 adult Pima Indians not taking hypoglycemic
      drugs. Among nondiabetic subjects, fasting plasma glucose (FPG) and 2-h postload
      plasma glucose (2-h PG) concentrations and categories of impaired glucose
      regulation or diabetes were evaluated as predictors of diabetes defined by 1999
      WHO criteria. RESULTS: The frequency of diabetes was 12.5% by 1997 ADA criteria,
      14.6% by 1985 WHO criteria, and 15.3% by 1999 WHO criteria. The incidence of
      diabetes was strongly related to higher FPG and 2-h PG, each of which had very
      similar predictive powers. Impaired glucose tolerance (IGT) was more common than
      impaired fasting glucose (IFG) (15 vs. 5%), but the 5-year incidence of diabetes
      was higher in IFG than IGT (37 vs. 24%). CONCLUSIONS: The prevalence and
      incidence of diabetes are somewhat lower with the ADA criteria than with the 1985
      or 1999 WHO criteria. The intermediate categories of glycemia differ
      substantially IFG defines a smaller number of people who are at higher risk of
      developing diabetes than those with IGT. More people at high risk of diabetes
      could be identified by using either IFG or IGT, as recommended by the 1999 WHO
      criteria, or by using the FPG concentration alone, but with a lower cutoff value.

PMID- 10937507
TI  - Plasma glucose and prediction of microvascular disease and mortality: evaluation
      of 1997 American Diabetes Association and 1999 World Health Organization criteria
      for diagnosis of diabetes.
AB  - OBJECTIVE: The 1997 American Diabetes Association (ADA) and 1999 World Health
      Organization (WHO) criteria for diabetes and hyperglycemia were evaluated and
      compared with respect to prediction of microvascular and macrovascular disease
      and mortality RESEARCH DESIGN AND METHODS: The prevalence of retinopathy and
      nephropathy at baseline and during the subsequent 10 years and mortality rates
      were examined in relation to baseline fasting plasma glucose (FPG) and 2-h
      postload plasma glucose (2-h PG) among 5,023 Pima Indian adults and in relation
      to the cut points defined by the ADA and WHO criteria. RESULTS: The frequencies
      of retinopathy and nephropathy were directly related to baseline FPG and 2-h PG
      with approximate thresholds near or below the current diagnostic criteria for
      diabetes (FPG > or =7.0 and 2-h PG > or = 11.1 mmol/l). The rates of retinopathy
      were 4.7% in impaired fasting glucose (IFG) and 20.9% in diabetes by ADA
      criteria; 1.6% for impaired glucose tolerance (IGT) and 19.7% for diabetes by
      1985 WHO criteria; and 1.2% for IGT and 19.2% for diabetes by the 1999 WHO
      criteria. Mortality rates from cardiovascular-renal-related diseases were higher
      in diabetic individuals (FPG > or =7.0 or 2-h PG > 11.1 mmol/l) than in those
      with normal FPG and 2-h PG but were not elevated in those with IFG or IGT.
      CONCLUSIONS: Retinopathy and nephropathy were directly related to higher FPG or 2
      h PG. FPG, which identifies those at high risk of microvascular disease and
      mortality, can be used to predict these outcomes and to diagnose diabetes when
      oral glucose tolerance testing is not practical.

PMID- 10937508
TI  - Diabetes duration and cause-specific mortality in the Verona Diabetes Study.
AB  - OBJECTIVE: To examine the 10-year mortality and effect of diabetes duration on
      overall and cause-specific mortality in diabetic subjects in the Verona Diabetes
      Study (VDS). RESEARCH DESIGN AND METHODS: Records from diabetes clinics, family
      physicians, and a drug consumption database were used to identify 5,818 subjects
      > or =45 years of age with type 2 diabetes who were alive and residing in Verona,
      Italy on 31 December 1986. Vital status of each subject was ascertained on 31
      December 1996. Underlying causes of death were determined from death
      certificates. Death rates and death rate ratios (DRRs) were computed and
      standardized to the population of Verona in 1991. RESULTS: During the study,
      2,328 subjects died; 974 deaths were attributable to cardiovascular disease, 517
      to neoplasms, 324 to diabetes-related diseases, 134 to digestive diseases, 250 to
      other natural causes, and 48 to external causes. There were 81 subjects who died
      of unknown causes. Death rates from natural causes were higher in men than in
      women (DRR 1.4, 95% CI 1.2-1.5) and rose in both sexes with increasing duration
      of diabetes (P = 0.001). Among the natural causes of death, those for diabetes
      related diseases were strongly related to diabetes duration (P = 0.001). a modest
      relationship with duration was also found for ischemic heart disease in men (P =
      0.07). CONCLUSIONS: Cardiovascular disease was the principal cause of death among
      people with type 2 diabetes in the VDS. Rates for natural causes of death rose
      with increasing duration of diabetes. Deaths from diabetes-related diseases in
      both sexes and from ischemic heart disease in men were largely responsible for
      this increase.

PMID- 10937509
TI  - Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl
      insulin complex in humans.
AB  - OBJECTIVE: To test whether a thyroxyl-insulin analog with restricted access to
      receptor sites in peripheral tissues displays relative hepatoselectivity in
      humans. RESEARCH DESIGN AND METHODS: Five normal human subjects received a
      subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins)
      or NPH insulin in random order. Insulin kinetics, relative effects on hepatic
      glucose production, and peripheral glucose uptake were studied using euglycemic
      clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples
      were taken for the determination of total immunoreactive insulin/analog
      concentrations and for liquid chromatography to assess the protein binding of the
      analog in the circulation. RESULTS: After subcutaneous administration, Bl-T4-Ins
      was well tolerated and rapidly absorbed. The analog had a long serum half-life
      and was highly protein bound (approximately 86%). Its duration of action, as
      judged by the duration of infusion of exogenous glucose to maintain euglycemia,
      was similar to that of NPH insulin. The effect of the analogs on hepatic glucose
      production was similar to that of NPH insulin, indicating equivalent hepatic
      potency. The analog demonstrated less effect on peripheral glucose uptake than
      NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose,
      and exhibited a reduced capacity to inhibit lipolysis (P < 0.05). CONCLUSIONS:
      When injected subcutaneously into normal human subjects, Bl-T4-Ins is well
      tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma
      halflife. This analog appears to have a hepatoselective action, and, therefore,
      has the potential to provide more physiological insulin action than the insulin
      preparations currently used.

PMID- 10937510
TI  - Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime
      insulin glargine compared with bedtime NPH insulin during insulin combination
      therapy in type 2 diabetes. HOE 901/3002 Study Group.
AB  - OBJECTIVE: Available basal insulin formulations do not provide a constant and
      reliable 24-h insulin supply. We compared the efficacy and safety of glargine (a
      long-acting insulin analog) and NPH insulins in insulin-naive type 2 diabetic
      patients treated with oral antidiabetic agents. RESEARCH DESIGN AND METHODS:
      There were 426 type 2 diabetic patients (age 59 +/- 9 years, BMI 28.9 +/- 4.3
      kg/m2, mean +/- SD) with poor glycemic control on oral antidiabetic agents
      randomized to treatment for 1 year with bedtime insulin glargine or bedtime NPH
      insulin. Oral agents were continued unchanged. The fasting blood glucose (FBG)
      target was 6.7 mmol/l (120 mg/dl). RESULTS: Average glycemic control improved
      similarly with both insulins (HbA(1c), [reference range <6.5%] 8.3 +/- 0.1 vs.
      8.2 +/- 0.1% at 1 year, glargine vs. NPH, mean +/- SEM, P < 0.001 vs. baseline
      for both). However, there was less nocturnal hypoglycemia (9.9 vs. 24.0% of all
      patients, glargine vs. NPH, P < 0.001) and lower post-dinner glucose
      concentrations (9.9 +/- 0.2 vs. 10.7 +/- 0.3 mmol/l, P < 0.02) with insulin
      glargine than with NPH. Insulin doses and weight gain were comparable. In
      patients reaching target FBG, HbA(1c) averaged 7.7 and 7.6% in the glargine and
      NPH groups at 1 year. CONCLUSIONS: Use of insulin glargine compared with NPH is
      associated with less nocturnal hypoglycemia and lower post-dinner glucose levels.
      These data are consistent with peakless and longer duration of action of insulin
      glargine compared with NPH. Achievement of acceptable average glucose control
      requires titration of the insulin dose to an FBG target < or =6.7 mmol/l. These
      data support use of insulin glargine instead of NPH in insulin combination
      regimens in type 2 diabetes.

PMID- 10937511
TI  - Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1
      diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type
      1 Diabetes Investigator Group.
AB  - OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human
      insulin) is a novel recombinant analog of human insulin with a shift in the
      isoelectric point producing a retarded absorption rate and an increased duration
      of action that closely mimics normal basal insulin secretion. It recently
      received approval from the Food and Drug Administration. The aim of this study
      was to evaluate 2 formulations of insulin glargine for safety and efficacy in the
      treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4
      week trial, 256 patients with type 1 diabetes received either NPH insulin or
      insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80
      microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously
      once daily at bedtime. NPH insulin was given either once daily (at bedtime) or
      twice daily (before breakfast and at bedtime), according to the patient's
      prestudy regimen. The initial doses of insulin glargine and NPH were based on the
      previous NPH total daily dose. RESULTS: At study end point, insulin glargine
      pooled groups had significantly lower fasting plasma glucose (FPG) levels than
      the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P =
      0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in
      patients who had previously received NPH insulin twice daily but not in patients
      who had previously received NPH once daily. FPG levels were more stable in
      patients using insulin glargine than in patients using NPH insulin. A subset of
      patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin
      glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was
      significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8
      mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both
      formulations of insulin glargine were well tolerated, similar to NPH insulin.
      CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part
      of a basal-bolus multiple daily insulin regimen was safe and more effective in
      lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.

PMID- 10937512
TI  - A new consensus error grid to evaluate the clinical significance of inaccuracies
      in the measurement of blood glucose.
AB  - OBJECTIVE: The objectives of this study were 1) to construct new error grids
      (EGs) for blood glucose (BG) self-monitoring by using the expertise of a large
      panel of clinicians and 2) to use the new EGs to evaluate the accuracy of BG
      measurements made by patients. RESEARCH DESIGN AND METHODS: To construct new EGs
      for type 1 and type 2 diabetic patients, a total of 100 experts of diabetes were
      asked to assign any error in BG measurement to 1 of 5 risk categories. We used
      these EGs to evaluate the accuracy of self-monitoring of blood glucose (SMBG)
      levels in 152 diabetic patients. The SMBG data were used to compare the new type
      1 diabetes EG with a traditional EG. RESULTS: Both the type 1 and type 2 diabetes
      EGs divide the risk plane into 8 concentric zones with no discontinuities. The
      new EGs are similar to each other, but they differ from the traditional EG in
      several significant ways. When used to evaluate a data set of measurements made
      by a sample of patients experienced in SMBG, the new type 1 diabetes EG rated
      98.6% of their measurements as clinically acceptable, compared with 95% for the
      traditional EG. CONCLUSIONS: The consensus EGs furnish a new tool for evaluating
      errors in the measurement of BG for patients with type 1 and type 2 diabetes.

PMID- 10937513
TI  - Multicenter evaluation of the Glucometer Elite XL meter, an instrument
      specifically designed for use with neonates.
AB  - OBJECTIVE: To evaluate the clinical performance of the Glucometer Elite XL
      Diabetes Care System in neonatal settings using a multicenter study RESEARCH
      DESIGN AND METHODS: A total of 388 blood specimens from 333 neonates were
      included in the study. A capillary or arterial sample was analyzed for
      determination of glucose with the Glucometer Elite XL system by an attending
      trained nurse. Through the same sampling site, a specimen was collected and sent
      to the laboratory for measurement of plasma glucose, bilirubin, and hematocrit.
      RESULTS: The regression analysis between the results of the Glucometer Elite XL
      system and comparative methods resulted in the following: Glucometer Elite XL
      meter = 1.01 x laboratory method + 0.02 mmol/l (n = 388). For the 1.1-4.0 mmol/l
      plasma glucose range, the regression was Glucometer Elite XL meter = 1.07 x
      laboratory method + 0.12 mmol/l (n = 150). A difference plot indicated a mean
      bias of 0.04 mmol/l (95% CI -0.01 to 0.10). No relationship was found between
      meter glucose biases and hematocrit levels (r = 0.10, P = 0.14). Although a
      statistically significant correlation existed between bilirubin levels and the
      glucose meter biases (r = 0.14, P = 0.005), the predicted mean biases were of
      little clinical significance. CONCLUSIONS: The Glucometer Elite XL system showed
      a good performance when used in neonatal settings.

PMID- 10937514
TI  - Bromocriptine: a novel approach to the treatment of type 2 diabetes.
AB  - OBJECTIVE: In vertebrates, body fat stores and insulin action are controlled by
      the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine
      modulates neurotransmitter action in the brain and has been shown to improve
      glucose tolerance and insulin resistance in animal models of obesity and
      diabetes. We studied the effect of a quick-release bromocriptine formulation on
      glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects.
      RESEARCH DESIGN AND METHODS: There were 22 obese subjects with type 2 diabetes
      randomized to receive a quick-release formulation of bromocriptine (n = 15) or
      placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a
      weight-maintaining diet to exclude any effect of changes in body weight on the
      primary outcome measurements. Fasting plasma glucose concentration and HbA(1c)
      were measured at 2- to 4-week intervals during treatment. Body composition
      (underwater weighing), body fat distribution (magnetic resonance imaging), oral
      glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose
      disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40
      and 160 mU x min(-1) x m(-2)) were measured before and after treatment. RESULTS:
      No changes in body weight or body composition occurred during the study in either
      placebo- or bromocriptine-treated subjects. Bromocriptine significantly reduced
      HbA(1c) (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172
      mg/dl, P = 0.02) levels, whereas these variables increased during placebo
      treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02,
      respectively). The differences in HbA(1c) (delta = 1.2%, P = 0.01) and fasting
      glucose (delta = 54 mg/dl, P < 0.001) levels between the bromocriptine and
      placebo group at 16 weeks were highly significant. The mean plasma glucose
      concentration during OGTT was significantly reduced by bromocriptine (from 294 to
      272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in
      glucose disposal occurred during the first step of the insulin clamp in either
      the bromocriptine- or placebo-treated group. During the second insulin clamp
      step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg x min(-1)
      kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3
      to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables
      deteriorated significantly (P < or = 0.02) in the placebo group. CONCLUSIONS:
      Bromocriptine improves glycemic control and glucose tolerance in obese type 2
      diabetic patients. Both reductions in fasting and postprandial plasma glucose
      levels appear to contribute to the improvement in glucose tolerance. The
      bromocriptine-induced improvement in glycemic control is associated with enhanced
      maximally stimulated insulin-mediated glucose disposal.

PMID- 10937515
TI  - Effect of acarbose on insulin sensitivity in elderly patients with diabetes.
AB  - OBJECTIVE: To study the effect of acarbose, an alpha-glucosidase inhibitor, on
      insulin release and insulin sensitivity in elderly patients with type 2 diabetes.
      RESEARCH DESIGN AND METHODS: Elderly patients with type 2 diabetes were randomly
      treated in a double-blind fashion with placebo (n = 23) or acarbose (n = 22) for
      12 months. Before and after randomization, subjects underwent a meal tolerance
      test and a hyperglycemic glucose clamp study designed to measure insulin release
      and sensitivity. RESULTS: After 12 months of therapy there was a significant
      difference in the change in fasting plasma glucose levels (0.2 +/- 0.3 vs. -0.5
      +/- 0.2 mmol/l, placebo vs. acarbose group, respectively; P < 0.05) and in
      incremental postprandial glucose values (-0.4 +/- 0.6 vs. -3.5 +/- 0.6 mmol/l,
      placebo vs. acarbose group, P < 0.001) between groups. There was a significant
      difference in the change in HbA(1c) values in response to treatment (0.4 +/- 0.2
      vs. -0.4 +/- 0.1%, placebo vs. acarbose group, P < 0.01). The change in fasting
      insulin in response to treatment (-2 +/- 2 vs. -13 +/- 4 pmol/l, placebo vs.
      acarbose group, P < 0.05) and incremental postprandial insulin responses (-89 +/-
      26 vs. -271 +/- 59 pmol/l, placebo vs. acarbose group, P < 0.01) was also
      significantly different between groups. During the hyperglycemic clamps, glucose
      and insulin values were similar in both groups before and after therapy However,
      there was a significant difference in the change in insulin sensitivity in
      response to treatment between the placebo and the acarbose groups (0.001 +/-
      0.001 vs. 0.004 +/- 0.001 mg/kg x min(-1) [pmol/l](-1), respectively, P < 0.05)
      CONCLUSIONS: Acarbose increases insulin sensitivity but not insulin release in
      elderly patients with diabetes.

PMID- 10937516
TI  - Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in
      patients in the early stage of diabetic nephropathy.
AB  - OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride
      affects the number of urinary podocytes in diabetic patients with
      microalbuminuria. RESEARCH DESIGN AND METHODS: Fifty patients with type 2
      diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30
      age-matched control subjects (18 men and 12 women, mean age 49.2 years) were
      included in the study. No patients showed serum creatinine levels in excess of
      2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with
      monoclonal antibodies against podocalyxin. RESULTS: Urinary podocytes were
      detected in 18 of the 50 microalbuminuric diabetic patients (mean, 1.3 cells/ml).
      Urinary podocytes were not detected in the remaining 32 patients or in the 30
      healthy control subjects. Diabetic patients positive for urinary podocytes were
      divided into 2 treatment groups: a dilazep dihydrochloride treatment group (300
      mg/day; n = 9, group A) and a placebo group (n = 9, group B). Treatments were
      continued for 6 months. In group A, microalbuminuria decreased significantly from
      146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and urinary podocytes also
      decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in group
      B, microalbuminuria and urinary podocytes changed little over the study period.
      CONCLUSIONS: Podocyte injury may occur in patients with early diabetic
      nephropathy, and dilazep dihydrochloride may be useful for preventing glomerular
      injury.

PMID- 10937517
TI  - Thalidomide impairs insulin action on glucose uptake and glycogen synthesis in
      patients with type 2 diabetes.
AB  - OBJECTIVE: To investigate the effect of thalidomide on glucose turnover (glucose
      production and uptake), on intracellular pathways of glucose utilization
      (glycogen synthesis [GS], glycolysis [GLS], carbohydrate oxidation, and
      nonoxidative GLS), and on free fatty acid (FFA) turnover (lipolysis, FFA
      oxidation, and FFA reesterification). RESEARCH DESIGN AND METHODS: A total of 6
      patients with type 2 diabetes were studied with 4-h isoglycemic-hyperinsulinemic
      clamps (approximately 8 mmol/l and 500-600 pmol/l, respectively) before treatment
      (Prestudy), after 3 weeks of thalidomide (150 mg orally at bedtime), and after 3
      weeks of placebo. RESULTS: Thalidomide reduced insulin-stimulated glucose uptake
      by 31% (from 27.7 to 19.2 pmol x kg(-1) x min(-1), P < 0.05) compared with the
      prestudy and by 21% (from 24.2 to 19.2 pmol x kg(-1) x min(-1), P < 0.05)
      compared with placebo. Thalidomide also reduced insulin-stimulated GS by 48%
      (from 14.1 to 8.2 micromol x kg(-1) x min(-1), P < 0.05) compared with the
      prestudy and by 40% (from 13.6 to 8.2 micromol x kg(-1) x min(-1), P < 0.5)
      compared with placebo. Thalidomide had no effect on rates of GLS, carbohydrate
      oxidation, nonoxidative GLS, lipolysis, FFA oxidation, and reesterification.
      CONCLUSIONS: We conclude that thalidomide increased insulin resistance in obese
      patients with type 2 diabetes by inhibiting insulin-stimulated GS and that
      patients taking thalidomide should be monitored for possible deterioration in
      their glucose tolerance.

PMID- 10937518
TI  - Autoimmunity against pancreatic islets and other tissues before and after
      interferon-alpha therapy in patients with hepatitis C virus chronic infection.
AB  - OBJECTIVE: The aim of the study was to investigate the prevalence of clinical and
      latent autoimmune diseases in Italian patients with hepatitis C virus (HCV)
      chronic infection before and after treatment with interferon-alpha (IFN-alpha).
      RESEARCH DESIGN AND METHODS: The evidence of clinical autoimmune disease and the
      presence of autoantibodies were assessed in 70 patients with HCV chronic
      infection. Autoantibodies to islet cell (ICA), glucagon-producing cells (GCA),
      parietal cell (PCA), adrenal cortex (ACA), adrenal medulla (AdMA), nuclei (ANA),
      liver-kidney microsomal (LKM-Ab), mitochondrial, and smooth muscle (SMA) were
      tested using the classic indirect immunofluorescence technique. Autoantibodies to
      GAD (GADAb), second islet cell autoantigen (IA2-Ab), and insulin (IAA) were
      tested by radioimmunoassay and thyroid microsomal autoantibodies (TMHA) and
      thyroglobulin autoantibodies (TGHA) were assessed by hemoagglutination test.
      RESULTS: None of the 70 patients studied showed evidence of clinical disease
      before treatment with IFN-alpha. However, 1 (1.4%) patient was positive for ICA,
      2 (2.8%) were positive for GCA, 2 (2.8%) for GADAb, 5 (7.1%) for PCA, 2 (2.8%)
      for ANA, 3 (3.7%) for SMA, 4 (5.7%) for TMHA, and 2 (2.8%) for TGHA. These
      frequencies were not significantly different when compared with healthy control
      subjects. There were 29 (41%) patients who were positive for IAA at low titers
      compared with 2% of the control subjects (significantly different P < 0.0001).
      ICA titers of one patient positive for ICA/GADAb increased during the IFN-alpha
      therapy, and the patient developed type 1 diabetes 5 months after the beginning
      of treatment. IAA levels did not change during the course of treatment, and none
      of the IAA+ patients developed diabetes. Thyroid autoantibody titers increased in
      3 of the 4 initially positive patients, with 1 patient becoming positive and 2
      thyroid antibody-positive patients developing overt hypothyroidism during IFN
      alpha treatment. PCA titers increased in 1 of 5 positive patients. Antibodies to
      other autoantigens did not change during the course of treatment. CONCLUSIONS: We
      have not found an increased frequency of clinical or latent autoimmune diseases
      in patients with chronic HCV infection. However, this study suggests that
      screening patients for autoantibodies (in particular, thyroid and pancreas)
      before and during IFN-alpha therapy may be useful in assessing the risk of
      patients developing autoimmune disease.

PMID- 10937519
TI  - Oxidative stress in families of type 1 diabetic patients.
AB  - OBJECTIVE: The link between hyperglycemia and the complications of diabetes is
      unknown. It is still discussed whether oxidative stress precedes or merely
      reflects diabetic complications. To search for a familial predisposition to
      oxidative stress, we investigated indexes of glucose and lipid metabolism,
      markers of plasma and cell lipid oxidation, a marker of oxidant-induced protein
      damage, and the effects of oxygen radicals on erythrocytes (or red blood cells
      [RBCs]) of patients with type 1 diabetes and their relatives. RESEARCH DESIGN AND
      METHODS: We recruited 30 type 1 diabetic subjects (10 without diabetic
      complications, 10 with retinopathy, and 10 with nephropathy), 36 nondiabetic
      siblings, 37 nondiabetic parents of type 1 diabetic subjects, and 3 control
      groups of healthy subjects without a family history of diabetes. Levels of blood
      creatinine, glucose, HbA(1c), cholesterol, triglycerides, lipoprotein(a) (Lp[a]),
      fibrinogen, malondialdehyde (MDA), and advanced oxidation protein products were
      determined. The RBC response to oxidative stress (3-h incubation at 37 degrees C
      with or without a radical generating system) was evaluated by measuring RBC
      glutathione (GSH), RBC-MDA, and hemolysis. RESULTS: Diabetic patients had higher
      levels of blood glucose (P < 0.001), HbA(1c) (P < 0.001), Lp(a) (P < 0.01), and
      fibrinogen (P < 0.05) than control subjects. Siblings of diabetic patients had
      higher Lp(a) levels (P < 0.001). Parents had higher levels of plasma glucose (P <
      0.05) and Lp(a) (P < 0.01). Plasma and RBC-MDA were significantly elevated in
      diabetic subjects and relatives compared with control subjects. Basal RBC-GSH was
      lower in diabetic subjects (P < 0.01). In diabetic subjects, incubations of cells
      caused a decrease in RBC-GSH of a lesser degree than that in control subjects,
      but they caused a significant increase in hemolysis. Among relatives, hemolysis
      was increased both at baseline and after incubation. Plasma MDA levels were
      associated with blood glucose, creatinine, and fibrinogen levels (multiple r =
      0.5, P < 0.001), and basal RBC-MDA levels were associated with plasma Lp(a),
      fibrinogen, and plasma MDA levels (r = 0.6, P < 0.001). Basal RBC-GSH content
      correlated with serum glucose and RBC-MDA production (r = 0.3, P < 0.01).
      CONCLUSIONS: Our study is the first to present evidence that markers of
      lipoprotein metabolism (Lp[a]), oxidative stress (plasma and RBC-MDA), and
      cellular fragility (hemolysis) are abnormal in nondiabetic relatives of type 1
      diabetic subjects, thereby supporting the view that familial elements of diabetes
      even precede the onset of diabetes. It seems reasonable that the same biological
      markers considered major predictors of cardiovascular disease can also trace
      familial susceptibility to type 1 diabetes, just as they have been associated
      with the development of type 2 diabetes.

PMID- 10937520
TI  - Evaluation of postural stability in elderly with diabetic neuropathy.
AB  - OBJECTIVE: The objective of this study was to compare clinical and biomechanical
      characteristics of balance in diabetic polyneuropathic elderly patients and
      normal age-matched subjects. RESEARCH DESIGN AND METHODS: Fifteen elderly with
      distal neuropathy (DNP) and 15 healthy age-matched subjects were evaluated with
      the biomechanical variable COP-COM, which represents the distance between the
      center of pressure (COP) and the center of mass (COM). Measurements were taken in
      the quiet position with a double-leg stance, in eyes-open (EO) and eyes-closed
      (EC) conditions. Subjects were also assessed with clinical balance evaluations.
      RESULTS: The COP-COM variable was statistically significantly larger in the DNP
      group than in the healthy group in anterior-posterior (A/P) and medial-lateral
      (M/L) directions. Furthermore, the DNP group showed statistically significantly
      larger amplitudes of the COP-COM variable without vision. The severity of the
      neuropathy, as quantified using the Valk scoring system, was correlated with COP
      COM amplitude in both directions. CONCLUSIONS: Evaluation of the postural
      stability of an elderly diabetic population using the COP-COM variable can detect
      a very small change in postural stability and could be helpful in identifying
      elderly with DNP at risk of falling.

PMID- 10937521
TI  - European Association for the Study of Diabetes Annual Meeting, 1999: the beta
      cell, autoimmunity, and insulin resistance.

PMID- 10937522
TI  - Hemoglobinopathies and HbA(1c) measurement.

PMID- 10937523
TI  - Improvement of glycemic control after treatment with mosapride for diabetic
      gastropathy.

PMID- 10937524
TI  - Response to training in blood glucose awareness is related to absence of previous
      hypoglycemic coma.

PMID- 10937525
TI  - Small-bowel bacterial overgrowth in diabetic subjects is associated with
      cardiovascular autonomic neuropathy.

PMID- 10937526
TI  - Thyroid autoimmunity starting during the course of type 1 diabetes denotes a
      subgroup of children with more severe diabetes.

PMID- 10937527
TI  - Diabetic ketoacidosis: a complication of type 2 diabetes in Canadian aboriginal
      youth.

PMID- 10937528
TI  - Interaction of gliclazide and rifampicin.

PMID- 10937529
TI  - No inverse relationship between total IgE levels and islet autoimmunity in
      children of parents with type 1 diabetes.

PMID- 10937530
TI  - Status of American Diabetes Association-funded research.

PMID- 10937531
TI  - GHb (HbA(1c)) is more sensitive than fasting blood glucose as a screening test
      for diabetes.

PMID- 10937532
TI  - Use of GHb (HbA(1c)) to screen for undiagnosed diabetes in the U.S. population.

PMID- 10937533
TI  - Transcutaneous glucose measurements using near-infrared spectroscopy: validation
      of statistical calibration models.

PMID- 10937534
TI  - "Real-life" driving behavior while hypoglycemic?

PMID- 10937535
TI  - Do psychogeriatricians 'neglect' religion? An antipodean survey.
AB  - BACKGROUND: Religion has been found to be important in the lives of many elderly
      people, but it has been claimed that psychiatrists 'neglect' the religious issues
      of their patients. This study examines the question: Do psychogeriatricians
      'neglect' religion in the assessment and treatment of their patients? METHOD: A
      sample of 207 psychiatrists with an interest in psychogeriatrics was surveyed
      using a 14-item questionnaire. Items addressed attitudes and behaviors of
      psychiatrists towards religion in relation to their clinical practice. RESULTS:
      Of the 143 (69%) who responded, 43% have no religious affiliation and only 25%
      participate at least monthly in organized religion. Nevertheless, 85% think that
      there are links between religion and mental health, and only one respondent
      stated that psychiatrists should never concern themselves with the religious
      issues of their patients. A total of 34%, however, had never referred a patient
      to a pastoral counselor. Training in religious issues is lacking. CONCLUSIONS:
      Psychogeriatricians think that religion is relevant in the assessment and
      treatment of elderly patients. In view of the lack of training in religious
      issues, revisions to the psychiatric training curriculum would be appropriate.
      This would promote dialogue between psychiatrists and religious caregivers.

PMID- 10937536
TI  - Characteristics of aggressive subjects in Australian (Melbourne) nursing homes.
AB  - BACKGROUND: Aggressive behavior is common in nursing homes for the elderly. It
      causes distress to carers and can lead to hospitalization, overmedication, and
      physical restraint. METHOD: A 6-month prospective study examining the
      characteristics of aggressive subjects in 11 nursing homes in Melbourne using
      validated, reliable instruments. RESULTS: During the study, 121 and 143 subjects
      were rated aggressive on the Rating Scale for Aggressive Behavior in the Elderly
      and the Staff Observation Aggression Scale, respectively. Aggressive behavior was
      associated with younger age, men, subsequent mortality, and prescription of
      psychotropic drugs including neuroleptics, antidepressants, and benzodiazepines.
      CONCLUSIONS: Educational programs in the use of psychotropic drugs directed at
      staff involved in the care of nursing home residents may be of value because
      these drugs have modest efficacy, have significant side effects, and may simply
      sedate the patient rather than treat aggressive behavior.

PMID- 10937537
TI  - Reliability, validity, and factor structure of the geriatric depression scale in
      Turkish elderly: are there different factor structures for different cultures?
AB  - The purpose of this study was to examine the Geriatric Depression Scale (GDS)
      translated into Turkish for its reliability, discriminant validity, and factor
      structure in a sample of 276 community-dwelling elderly and 30 patients with
      major depression. One item (Item 5) was discovered to have conceptual difficulty
      for Turkish elderly and was transformed to negative form. Item 2 was transformed
      to positive form to keep the number of positive and negative items equal to that
      in the original GDS. A reasonable time stability with 1-week interval (r: .74)
      and a high level of internal consistency (alpha=.91) were observed. Student's t
      test resulted in a significant discriminant validity for the scale total score.
      Factor study with principal component analysis and varimax rotation gave rise to
      a structure with seven factors. Results of the same analysis with two factors
      were found to be easier to interpret. The first factor was composed of 19 items
      reflecting "depressive affect and thought content." The other 11 items
      representing "decrease in motivation and cognitive functions" loaded in the
      second factor. In conclusion, the Turkish GDS was found to have reasonable time
      reliability, high internal consistency, and discriminant validity for Turkish
      elderly. Its two-factor structure can be used as an informative instrument for
      epidemiological studies, reflecting two main dimensions of depression in the
      elderly.

PMID- 10937538
TI  - A new version of the geriatric depression scale for nursing and residential home
      populations: the geriatric depression scale (residential) (GDS-12R).
AB  - The objective was to develop a new short-form Geriatric Depression Scale (GDS
      12R) suitable for older people living in nursing and residential care settings,
      including those persons with significant cognitive impairment. A total of 308
      newly admitted residents of 30 nursing and residential homes in northwest England
      were interviewed using the Geriatric Depression Scale (GDS-15), the Mini-Mental
      State Examination, and the Affect Balance Scale (ABS). A 12-item version of the
      GDS was shown to have greater internal reliability than the 15-item version,
      because of the context-dependent nature of the deleted items. There was close
      agreement between the GDS-12R items and another indicator of depressed mood (a
      single item from the ABS). Furthermore, moderate to high levels of cognitive
      impairment did not affect the performance of the new version of the scale. The
      GDS-12R provides researchers and clinicians with a brief, easy-to-administer
      depression scale that is relevant to residential and nursing home populations.

PMID- 10937539
TI  - Factors predicting chronicity of depression in elderly primary care patients.
AB  - AIM: The aim was to identify the factors predicting and related to chronicity of
      depression among depressed Finnish elderly subjects. MATERIAL AND METHODS: The
      study consisted of 97 depressed (DSM-III criteria) elderly (60 years or older)
      Finns treated in primary health care. The occurrence of depression was assessed
      after treatment and follow-up periods of about 15 months and 5 years, and the
      persons were classified according to their recovery: (a) persons depressed in all
      the three examinations (the chronically depressed) (n = 47), and (b) persons
      depressed in the first examination, but nondepressed in both follow-up
      examinations (the recovered) (n = 50). RESULTS: Diurnal variation of symptoms and
      poor self-appreciation at the baseline and the onset of a severe disease, the
      deterioration of one's health status, and the death of a family member during the
      follow-up emerged as independent predictors or associates of the chronic course
      of depression in the logistic regression model. CONCLUSIONS: Depressed elderly
      subjects who develop a physical disease or whose family member dies during the
      treatment of depression have a high risk for a chronic course. Intensive
      antidepressant and psychotherapeutic treatment and adequate physical treatment of
      these patients are proposed, in order to increase the probability of recovery
      from depression.

PMID- 10937540
TI  - Validation of the epidemiological dementia index in geriatric outpatients.
AB  - The aim of the current study was to test the properties of a scale especially
      developed for use in epidemiological surveys in low sociocultural populations,
      and to determine whether this scale can be used in a clinical population.
      MATERIAL AND METHODS: Two hundred fifty subjects took part; 150 were controls and
      100 had dementia of various types according to DSM-IV and NINCDS-ADRDA criteria.
      RESULTS: Cronbach's alpha was equal to .78. In the group of people under 75 years
      old, sensitivity did not exceed 90%. Specificity was over 90% at the level 4/5.
      The respective scores for the group of people over 74 were 6/7 and 3/4.
      DISCUSSION: The Epidemiological Dementia Index seems to be less powerful when
      used in a clinical population. This provides further evidence that it is not
      suitable to use the same instruments in both epidemiological studies and clinical
      practice.

PMID- 10937541
TI  - Elderly suicide in Finland.
AB  - Suicide mortality among the elderly is high in most Western countries. We
      investigated the characteristics of suicide victims 65 years or older in a
      nationwide psychological autopsy study, the research phase of the National
      Suicide Prevention Project in Finland. This study population included all
      completed suicides (N = 1,397, of whom 211 were 65 years or older) that occurred
      in Finland during a 12-month research period in 1987-1988. The elderly suicide
      victims were found to have used violent suicide methods more often than the
      young. Although almost 70% of the elderly persons who had committed suicide had
      been in contact with health care services during the month before their death,
      their suicidal intentions were rarely communicated in these contacts. They had
      been referred to psychiatric services less often than the young, and only 8% had
      received adequate antidepressive medication. The fact that most elderly suicides
      have contact with health care services during their final month suggests a
      potential for suicide prevention. However, the major obstacle to this is the poor
      recognition of mental disorders and suicidal ideation among the elderly.

PMID- 10937542
TI  - On telling the truth in Alzheimer's disease: a pilot study of current practice
      and attitudes.
AB  - Research suggests there has been a cultural change in the disclosure of
      diagnosis; most evidence relates to cancer and there is little knowledge of
      attitudes towards disclosing the diagnosis of Alzheimer's disease. A
      questionnaire was used to survey the current practice and attitudes of old-age
      psychiatrists and geriatricians in Nottingham, UK. The results of this pilot
      study suggest that only 40% of respondents regularly tell patients the diagnosis.
      Although physicians are aware of many benefits in disclosing, they have concerns
      regarding the certainty of diagnosis, the patient's insight, and potential
      detrimental effects. The advantages of disclosure and the ethical issues involved
      are discussed.

PMID- 10937543
TI  - Tracking cognitive decline in Alzheimer's disease using the mini-mental state
      examination: a meta-analysis.
AB  - OBJECTIVES: To estimate the annual rate of change scores (ARC) on the Mini-Mental
      State Examination (MMSE) in Alzheimer's disease (AD) and to identify study or
      population characteristics that may affect the ARC estimation. METHODS: MEDLINE
      was searched for articles published from January 1981 to November 1997 using the
      following keywords: AD and longitudinal study or prognosis or cognitive decline.
      The bibliographies of review articles and relevant papers were searched for
      additional references. All retrieved articles were screened to meet the following
      inclusion criteria: (a) original study; (b) addressed cognitive decline or
      prognosis or course of AD; (c) published in English; (d) study population
      included AD patients with ascertainable sample size; (e) used either clinical or
      pathological diagnostic criteria; (f) longitudinal study design; and (g) used the
      MMSE as one of the outcome measures. Data were systematically abstracted from the
      included studies, and a random effects regression model was employed to
      synthesize relevant data across studies and to evaluate the effects of study
      methodology on ARC estimation and its effect size. RESULTS: Of the 439 studies
      screened, 43 met all the inclusion criteria. After 6 studies with inadequate or
      overlapping data were excluded, 37 studies involving 3,492 AD patients followed
      over an average of 2 years were included in the meta-analysis. The pooled
      estimate of ARC was 3.3 (95% confidence interval [CI]: 2.9-3.7). The observed
      variability in ARC across studies could not be explained with the covariates we
      studied, whereas part of the variability in the effect size of ARC could be
      explained by the minimum MMSE score at entry and number of assessments.
      CONCLUSIONS: A pooled average estimate of ARC in AD patients was 3.3 points (95%
      CI: 2.9-3.7) on the MMSE. Significant heterogeneity of ARC estimates existed
      across the studies and cannot be explained by the study or population
      characteristics investigated. Effect size of ARC was related to the initial MMSE
      score of the study population and the number of assessments.

PMID- 10937544
TI  - Coping with dementia: evaluation of four nonpharmacologic interventions.
AB  - To evaluate nonpharmacologic interventions, caregivers (65 women, 38 men) and
      their dementia-diagnosed spouses (patients) were randomized to one of four
      treatment programs (cognitive stimulation, dyadic counseling, dual supportive
      seminar, and early-stage day care) or to a wait-list control group. Assessments
      occurred initially and at postintervention (3 months). Patients were evaluated on
      memory, verbal fluency, and problem-solving ability, and caregivers were assessed
      on marital interaction, emotional status, and physical health, along with stress,
      coping, and social support. Caregivers also completed a program evaluation.
      Repeated measures procedures showed that patients in the cognitive stimulation
      group demonstrated more improvement over time in cognitive outcomes, and
      caregivers decreased in depressive symptoms. Early-stage day-care and dual
      supportive seminar group caregivers reported a decrease in hostility and a
      decrease in use of negative coping strategies, respectively. Although
      qualitatively derived benefits differed across groups, similarities in program
      content reduced the potential for quantitative differentiation among the groups.

PMID- 10937545
TI  - Excess disability during morning care in nursing home residents with dementia.
AB  - Excess disability was examined in 17 nursing home residents with dementia by
      comparing their performance of morning care tasks under two activities of daily
      living (ADL) caregiving approaches-a dependence-supportive one under usual care
      and an independence-supportive one under functional rehabilitation. The results
      suggest that excess disability in severely cognitively impaired and functionally
      disabled residents can be reduced by increasing opportunities for independent
      activity, and substituting nondirective and directive verbal assists for physical
      assists. Further, the findings indicate that increased independence in ADL can be
      achieved without increasing disruptive behaviors and can foster appropriate
      requests for task-related help during caregiving. Functional rehabilitation,
      however, requires more time than usual care.

PMID- 10937546
TI  - Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental
      eyelid malignant melanoma.
AB  - PURPOSE: To determine the effect of adenovirus-mediated gene transfer of a
      soluble receptor of vascular endothelial growth factor (VEGF) on the growth of
      experimental eyelid malignant melanoma. METHODS: An adenovirus vector encoding a
      soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal
      endothelial cells (ECs) were incubated in a culture medium of 293E1 cells
      infected by means of an adenovirus vector or uninfected (control), which
      contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The
      experimental eyelid malignant melanoma was induced by the injection of B16
      melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu
      mice, and the size of the tumor was recorded for 3 weeks after tumor cell
      injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells
      were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of
      10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre
      established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was
      injected into the femoral muscle of mice before B16 cell injection into the
      eyelid, and the remote effect was evaluated. An adenovirus vector bearing the
      LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount
      of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked
      immunosorbent assay (ELISA). Vascularization was evaluated by counting the number
      and the size of the vessels. RESULTS: The supernatant of Adflt-ExR-transfected
      cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In
      models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly
      lower than that of controls (P < 0.05). In model 3, no significant difference was
      found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the
      tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3
      (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer
      vessels than tumors in control animals in models 1 and 2 (P < 0.05). CONCLUSIONS:
      Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene
      inhibited the growth of the experimental eyelid malignant melanoma. This method
      may be useful as an antiangiogenic therapy for eyelid malignant melanoma.

PMID- 10937548
TI  - Injury-specific expression of activating transcription factor-3 in retinal
      ganglion cells and its colocalized expression with phosphorylated c-Jun.
AB  - PURPOSE: To ascribe activating transcription factor (ATF)-3 as a specifically
      induced transcription factor after ON injury and to describe its putative role as
      a modulator of c-Jun transactivation. METHODS: The adult rat optic nerve was
      crushed intraorbitally, and expression profiles of ATF-3, ATF-2, and
      phosphorylated c-Jun (p-c-Jun) were examined by immunohistochemistry and ISH.
      Western blot analysis for ATF-3 and -2 were also performed. Furthermore,
      colocalized detection of c-Jun mRNA with ATF-2 or -3 was attempted with a
      combined method of simultaneous immunohistochemistry and in situ hybridization.
      RESULTS: In response to optic nerve injury, substantial expression of ATF-3 as
      well as that of p-c-Jun was observed in the retinal ganglion cells, whereas no
      expression of ATF-3 was seen in other noninjured retinal cells. In contrast, ATF
      2 was normally expressed abundantly in both retinal ganglion cells and displaced
      amacrine cells, but expression dropped in retinal ganglion cells after nerve
      injury. The expression profiles of ATF-2 and -3 after optic nerve injury were
      confirmed by Western blot analysis. A higher degree of colocalization was
      observed for ATF-3 and c-Jun than the modest codetection for ATF-2 and c-Jun.
      CONCLUSIONS: The transcription factor ATF-3 is specifically induced upon optic
      nerve injury and colocalizes with p-c-Jun in surviving ganglion cells. These
      findings suggest that both ATF-3 and c-Jun are crucial to trigger various
      transcriptional responses and may act synergistically during the survival phase
      of the optic nerve in the injury model.

PMID- 10937547
TI  - Inhibition of conjunctival scarring and contraction by a porous collagen
      glycosaminoglycan implant.
AB  - PURPOSE: To study the healing processes of full-thickness wounds in the adult
      rabbit conjunctiva after grafting with a porous collagen-glycosaminoglycan (CG)
      copolymer matrix. METHODS: A 7-mm trephine was used to produce lesions of the
      bulbar conjunctiva down to the level of the bare sclera. Full-thickness removal
      of the conjunctiva and Tenon's capsule created a reproducible wound bed. Wounds
      either remained ungrafted (control) or were grafted with CG matrix. In previous
      studies, this CG matrix has induced partial regeneration of the dermis in the
      human, the swine, and the guinea pig. Healing of the conjunctival epithelium and
      underlying stroma was evaluated by histology, immunohistochemistry, and
      measurement of wound contraction kinetics. RESULTS: By 28 days, ungrafted wounds
      had closed by contraction (26.4% +/- 5.0% fornix shortening) and the formation of
      scarlike tissue comprising an aligned array of dense collagen populated with
      occasional fibroblasts. Grafting of identical defects with CG copolymer matrix
      resulted in inhibition of wound contraction (6.8% +/- 3.2% fornix shortening) and
      the formation of a tissue that resembled normal conjunctival stroma, being
      composed of a loose network of collagen fibers and fibroblasts. Contractile
      fibroblasts (myofibroblasts) were identified at the edge of both ungrafted and
      grafted wounds during the period of active contraction. Both ungrafted and
      grafted wounds were completely re-epithelialized by 28 days. CONCLUSIONS:
      Implantation of CG copolymer matrix drastically reduced contraction and promoted
      the formation of a nearly normal subconjunctival stroma.

PMID- 10937549
TI  - Innervated myotendinous cylinders in human extraocular muscles.
AB  - PURPOSE: To analyze palisade endings and their end organs, the so-called
      innervated myotendinous cylinders (IMCs), of human extraocular muscle (EOM) in
      more detail and to clarify with the help of double-fluorescent labeling and
      electron microscopy whether terminals in IMCs are sensory, serving
      proprioception. METHODS: EOMs obtained from a donated cadaver (66 years) and
      distal parts of EOMs from multiorgan donors (35, 53 years) were processed for
      double-fluorescent labeling. Antibodies against the protein gene product 9.5 and
      alpha-bungarotoxin labeling were used on cryostat sections of distal myotendons.
      EOMs from multiorgan donors (2, 17 years) were prepared for electron microscopy.
      RESULTS: Palisade endings investing muscle fiber tips established contacts with
      tendon fibrils and the muscle fiber attached. Alpha-bungarotoxin bound to
      myoneural contacts but not to axonal varicosities in the tendon compartment.
      Ultrastructural analysis revealed that palisade endings form IMCs, which were
      associated exclusively with multiply innervated global layer muscle fibers. IMCs
      consisted of a muscle fiber tendon junction, tightly enclosed by fibrocytes, and
      a supplying axon with preterminals and terminals. Terminals contained
      mitochondria, few neurotubuli, few neurofilaments, and accumulations of clear
      vesicles of uniform size. A basal lamina always intervened between axolemma and
      tendon fibrils as well as between axolemma and muscle fiber cell membrane.
      CONCLUSIONS: Palisade endings of human EOM form IMCs as in cat, monkey, and
      sheep. In contrast to animals, myoneural contacts in human IMCs are almost
      certainly motor, whereas terminals contacting tendon fibrils are arguably
      sensory. Thus, IMCs might be best described as "propriocept-effectors."

PMID- 10937550
TI  - Leakage of aquaporin 5 in the tear of dacryoadenitis mice.
AB  - PURPOSE: The objective of this study was to investigate whether leakage of
      aquaporin 5 (AQP5) in tear is associated with damage of lacrimal glands (LGs) in
      dacryoadenitis models. METHODS: Female MRL/lpr (24-week-old), male NOD/Shi Jci (5
      , 8-, and 10-week-old), female NFS/s-TX (10-week-old), and lipopolysaccharide
      (LPS)-induced dacryoadenitis model mice were used. Tear fluid was collected by a
      cotton thread. Tear proteins in the thread were dissolved in sodium dodecyl
      sulfate buffer, and AQP5 proteins were analyzed by the Western blot technique
      using anti-AQP5 antibody. LGs were prepared for hematoxylin and eosin staining or
      immunostaining of AQP5. RESULTS: In MRL/lpr, NFS/s-TX, 8- and 10-week-old NOD/Shi
      Jci mice, AQP5 protein was detected in the tear by Western blot analysis.
      Inflammatory lymphocyte infiltrations were observed in LGs of these
      dacryoadenitis model mice. In contrast, AQP5 leakage and damage of LG were not
      observed in normal mice. In 5-week-old NOD/Shi Jci mice, infiltration was not
      seen in LG, and AQP5 leakage was not detected in the tear. In LPS-induced
      dacryoadenitis model mice, either tissue destruction with inflammation in LG or
      AQP5 leakage in the tear was observed. AQP5 in the tear and tissue inflammation
      in LGs was not found in control mice. These results indicate that AQP5 is leaked
      in tears when LGs are damaged by dacryoadenitis. CONCLUSIONS: Leakage of AQP5 in
      the tear was found to be related to LG damage. This finding suggests that
      detection of AQP5 in tear is useful for specific diagnosis of LG disorders with
      tissue destruction.

PMID- 10937551
TI  - Osteonectin/SPARC secreted by RPE and localized to the outer plexiform layer of
      the monkey retina.
AB  - PURPOSE: Osteonectin/SPARC is a secreted protein that has been implicated in
      ocular disease. Deletion of osteonectin/SPARC causes age-onset cataract in mice
      and the cataractous human lens has increased expression of osteonectin/SPARC. In
      this study, the expression and localization of osteonectin/SPARC in the monkey
      retina were determined as was secretion by cultured human retinal pigment
      epithelial (RPE) cells. METHODS: Adult Rhesus monkey eyes (Macaca mulatta) were
      dissected, and 5-mm macula and peripheral retina punches were obtained.
      Supernatants were collected from cultured human RPE cells. Subcellular
      fractionation of whole monkey retina was also performed. Osteonectin/SPARC
      expression and/or secretion was monitored by Northern and Western blot analyses,
      and localization was determined by immunocytochemistry. RESULTS: Outside of the
      retina osteonectin/SPARC mRNA is broadly expressed in many human tissues.
      Northern blot analysis shows that in the retina osteonectin/SPARC is expressed
      almost exclusively by the macular RPE/choroid. Western blot analysis revealed
      osteonectin/SPARC in both the macula and the peripheral neural retina but only in
      trace amounts in the RPE/choroid. In subcellular fractions of the whole retina,
      osteonectin/SPARC was detected, mainly in the soluble fraction but also in the
      membrane and nuclear fractions. Immunohistochemical analysis localized
      osteonectin/SPARC specifically to the outer plexiform layer. Western blot
      analysis of conditioned medium from human RPE cells cultured on porous substrates
      indicated that osteonectin/SPARC is secreted in large amounts from both the
      apical and basal sides of the RPE. CONCLUSIONS: Collectively these data provide
      evidence that osteonectin/SPARC is synthesized in the macular RPE, secreted, and
      subsequently transported to the outer plexiform layer. The expression pattern of
      osteonectin/SPARC in the subcellular retinal fractions is consistent with a
      soluble protein that is transported and internalized.

PMID- 10937552
TI  - Cloning and functional characterization of salamander rod and cone arrestins.
AB  - PURPOSE: To clone, localize, and determine functional binding characteristics of
      rod and cone arrestins from the retina of the tiger salamander (Ambystoma
      tigrinum). METHODS: Two arrestins from salamander retina were cloned on the basis
      of their homology to known arrestins from other species. The expression pattern
      of these arrestins (SalArr1 and SalArr2) in the retina was determined by
      immunocytochemistry and in situ hybridization. SalArr1 and SalArr2 were expressed
      and functionally characterized. RESULTS: Both immunocytochemistry and in situ
      hybridization show that SalArr1 and SalArr2 localized specifically to rod and
      cone photoreceptors, respectively. SalArr1 demonstrated a characteristic high
      selectivity for light-activated phosphorylated rhodopsin (P-Rh*) and significant
      species selectivity, binding preferentially to amphibian rhodopsin over bovine
      rhodopsin. Mutant constitutively active forms of SalArr1 demonstrated a 2- to 4
      fold increase in P-Rh* binding (compared with wild-type protein) and an even more
      dramatic (up to 25-fold) increase in binding to unphosphorylated Rh* and dark P
      Rh. Constitutively active SalArr1 mutants also showed a reduced specificity for
      amphibian rhodopsin. The ability of Escherichia coli-expressed SalArr1, SalArr2,
      and an SalArr1-3A (L369A,V370A,F371A) mutant to bind to frog Rh* and P-Rh* and to
      compete with tritiated SalArr1 for amphibian P-Rh* was compared. SalArr1 and its
      mutant form bound to amphibian P-Rh* with high affinity (Ki = 179 and 74 nM,
      respectively), whereas the affinity of SalArr2 for P-Rh* was substantially lower
      (Ki = 9.1 microM). CONCLUSIONS: SalArr1 and SalArr2 are salamander rod and cone
      arrestins, respectively. Crucial regulatory elements in SalArr1 are conserved and
      play functional roles similar to those of their counterparts in bovine rod
      arrestin. Rod and cone arrestins are relatively specific for their respective
      receptors.

PMID- 10937554
TI  - Protein oxidation and lens opacity in humans.
AB  - PURPOSE: Oxidative damage to lens proteins is a major factor leading to cataract
      formation. It is of pathogenic importance to determine a threshold of protein
      oxidation over which opacification of the lens takes place. METHODS: Sixty-two
      lenses extracted from patients affected by idiopathic senile, diabetic, or myopic
      cataract were studied. Clear lenses were obtained from subjects undergoing
      enucleation (n = 10) or vitrectomy for giant retinal tears (n = 9), and were age-
      and sex-matched to those with cataract. The content of carbonyls and sulfhydryls
      (P-SH) in proteins in the lens was assessed using spectrophotometric assay.
      RESULTS: An age-associated inverse relation (P < 0.01) was noted in the content
      of P-SH, the concentrations of which were also inversely related (P < 0.03) to
      the content of protein carbonyls. These changes were more pronounced in cataracts
      than in clear lenses and in diabetic and myopic cataracts when compared with
      senile cataracts. The drop of P-SH concentration occurred earlier in diabetic and
      in myopic cataracts than in senile cataracts. The accumulation of protein
      carbonyls > 2 nmol/mg protein and the decrease of P-SH below 12 to 10 nmol/mg
      protein were always accompanied by lens opacification. CONCLUSIONS: Idiopathic
      senile, diabetic, and myopic cataractogenesis appear to be dependent on oxidative
      damage to lens proteins. This damage occurs earlier in myopic and diabetic
      patients. Values of P-SH below and protein carbonyls above their specific
      threshold were found to be predictive for the presence of cataract. Because
      increased oxidation was observed in clear lenses removed from myopic and diabetic
      subjects, oxidation may be involved in the pathogenesis of these forms of human
      cataract.

PMID- 10937553
TI  - Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2
      mutations.
AB  - PURPOSE: Rieger syndrome is an autosomal dominant condition characterized by a
      variable combination of anterior segment dysgenesis, dental anomalies, and
      umbilical hernia. To date, reports have shown mutations within the PITX2 gene
      associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The
      purposes of this study were to determine the range of expression and
      intrafamilial variability of PITX2 mutations in patients with anterior segment
      dysgenesis. METHODS: Seventy-six patients with different forms of anterior
      segment dysgenesis were classified clinically. DNA was obtained and screened by
      means of polymerase chain reaction (PCR)-single-stranded conformation
      polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing.
      RESULTS: Eight of 76 patients had mutations within the PITX2 gene. Anterior
      segment phenotypes show wide variability and include a phenocopy of aniridia and
      Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations
      and splice-site and homeobox mutations, confirming that haploinsufficiency the
      likely pathogenic mechanism in the majority of cases. CONCLUSIONS: There is
      significant phenotypic variability in patients with PITX2 mutations, both within
      and between families. Developmental glaucoma is common. The umbilical and dental
      abnormalities are highly penetrant, define those at risk of carrying mutations in
      this gene, and guide mutation analysis. In addition, there is a range of other
      extraocular manifestations.

PMID- 10937555
TI  - Rapid detection of M1S1 mutations by the protein truncation test.
AB  - PURPOSE: To determine a method of rapid detection of M1S1 gene mutations in
      patients with gelatinous droplike corneal dystrophy. METHODS: Forty-one patients
      from 35 families with gelatinous drop-like corneal dystrophy were studied. The
      entire coding region of the M1S1 gene was screened using the protein truncation
      test (PYT), with a polymerase chain reaction fragment amplified from genomic DNA
      serving as a template of in vitro translation. RESULTS: Homozygous or compound
      heterozygous mutations were detected in all patients by a single reaction of the
      PTT. This result matched those obtained using the polymerase chain reaction
      restriction fragment length polymorphism and direct sequence analyses. The Q118X
      mutation was present in 63 of the 70 alleles, accounting for 90% of the disease
      associated chromosomes in Japanese patients. CONCLUSIONS: The PTT is useful for
      detecting mutations in the M1S1 gene. This technique showed that the Q118X
      mutation is a founder mutation in Japanese patients with gelatinous droplike
      corneal dystrophy, and it reflects the linkage disequilibrium reported
      previously.

PMID- 10937556
TI  - AC/A ratio, age, and refractive error in children.
AB  - PURPOSE: To examine how the response AC/A ratio (the amount of accommodative
      convergence per unit of accommodative response) varies as a function of
      refractive error and age, to determine whether it is a risk factor for the onset
      of myopia, and to examine the relation between ocular structural features and the
      AC/A ratio. METHODS: Accommodation was stimulated by a letter target presented in
      a Badal system at 0.00, 2.25, and 4.37 D to 828 children aged 6 through 14 years
      in 1996. Of these, 726 had no myopia in 1996 and were available for examination
      the following year. Accommodative response and cycloplegic refractive error were
      measured by autorefraction and convergence by monitoring the relative movement of
      Purkinje images I and IV. Lens radii of curvature were measured by video
      phakometry, corneal radius of curvature by topography, and ocular axial
      dimensions by A-scan ultrasonography. RESULTS: Adjusted for age, the response
      AC/A ratio was highest in myopes (6.39 delta/D), intermediate in emmetropes (3.94
      delta/D), and lowest in hyperopes (3.40 delta/D; P < 0.0001; two-way analysis of
      variance [ANOVA]). The stimulus AC/A ratio did not vary with refractive error.
      Adjusted for refractive error, the response AC/A ratio did not change as a
      function of age. In non-myopic children, having a response AC/A ratio of 5.84
      delta/D or more elevated the risk of development of myopia within 1 year by 22.5
      times (95% CI = 7.12-71.1). In a subsample of children without myopia who had
      refractive errors less than +0.75 D, having a response AC/A ratio of 5.84 delta/D
      or more elevated the risk of development of myopia within 1 year by 3.21 times
      (95% CI = 1.14-9.07). The AC/A ratio was associated with all measured ocular
      features except lens spherical volume. Only the negative correlations with
      refractive error and the shape of the crystalline lens (Gullstrand lens power)
      were significant in a multiple regression model (adjusted R2 = 0.16).
      CONCLUSIONS: An elevated response AC/A ratio was associated with myopia and was
      an important risk factor for its rapid onset. The association between higher AC/A
      ratios and flatter crystalline lens shapes, as well as other reported features of
      accommodation in myopia, may be explained by "pseudocycloplegia," which the
      authors define as tension on the crystalline lens that increases the level of
      effort needed to accommodate. Accommodative deficits in myopia may be the
      functional consequences of the underlying anatomy of the enlarged eye.

PMID- 10937557
TI  - The effect of age, size of target, and cognitive factors on accommodative
      responses of children with Down syndrome.
AB  - PURPOSE: To investigate possible factors that may be implicated in the poor
      accommodative responses of individuals with Down syndrome. This article evaluates
      the effect of age, angular size of target, and cognitive factors on
      accommodation. METHODS: Seventy-seven children with Down syndrome who are
      participating in an ongoing study of visual development were assessed. One
      hundred thirty-one developmentally normal children took part in a previous study
      and provided control data. Accommodation was measured using a modified Nott
      dynamic retinoscopy technique. RESULTS: Children with Down syndrome showed
      considerably poorer accommodative responses than normally developing children. No
      target used in the present study produced an improved response in children with
      Down syndrome. Age, angular subtense of target, and cognitive factors could not
      fully account for the poor accommodation in children with Down syndrome.
      CONCLUSIONS: Poor accommodation is a common feature of Down syndrome, regardless
      of the target used. The etiology of the deficit has yet to be established. It is
      imperative that educators and clinicians are aware that near vision is out of
      focus for these children.

PMID- 10937558
TI  - Prevalence and risk factors for refractive errors in adult Chinese in Singapore.
AB  - PURPOSE: To determine the epidemiology of refractive errors in an adult Chinese
      population in Singapore. METHODS: A disproportionate, stratified, clustered,
      random-sampling procedure was used to select names of 2000 Chinese people aged 40
      to 79 years from the 1996 Singapore electoral register in the Tanjong Pagar
      district in Singapore. These people were invited to a centralized clinic for a
      comprehensive eye examination, including refraction. Refraction was also
      performed on nonrespondents in their homes. Myopia, high myopia, and hyperopia
      were defined as a spherical equivalent (SE) in the right eye of less than -0.5 D,
      less than -5.0 D, and more than +0.5 D, respectively. Astigmatism was defined as
      less than -0.5 D of cylinder. Anisometropia was defined as a difference in SE of
      more than 1.0 D between the two eyes. Only phakic eyes were analyzed. RESULTS:
      From 1717 eligible people, 1232 (71.8%) were examined. Adjusted to the 1997
      Singapore population, the overall prevalence of myopia, hyperopia, astigmatism,
      and anisometropia was 38.7% (95% confidence interval [CI]: 35.5, 42.1), 28.4%
      (95% CI: 25.3, 31.3), 37.8% (95% CI: 34.6, 41.1), and 15.9% (95% CI: 13.5, 18.4),
      respectively. The prevalence of high myopia was 9.1% (95% CI: 7.2, 11.2), with
      women having significantly higher rates than men. The age pattern of myopia was
      bimodal, with higher prevalence in the 40 to 49 and 70 to 81 age groups and lower
      prevalence between those age ranges. Prevalence was reversed in hyperopia, with a
      higher prevalence in subjects aged 50 to 69. There was a monotonic increase in
      prevalence with age for both astigmatism and anisometropia. Increasing
      educational levels, higher individual income, professional or office-related
      occupations, better housing, and greater severity of nuclear opacity were all
      significantly associated with higher rates of myopia, after adjustment for age
      and sex. CONCLUSIONS: The results indicate that whereas myopia is 1.5 to 2.5
      times more prevalent in adult Chinese residing in Singapore than in similarly
      aged European-derived populations in the United States and Australia, the
      sociodemographic associations are similar.

PMID- 10937559
TI  - Coordinated reassembly of the basement membrane and junctional proteins during
      corneal epithelial wound healing.
AB  - PURPOSE: To characterize changes in the localizations of the basement membrane
      protein laminin-1 and of adhesion proteins of intercellular junctions during
      wound healing after epithelial ablation in the rat cornea. METHODS: Epithelial
      ablation was performed with an excimer laser. Rats were killed immediately, 12
      hours, 24 hours, 3 days, or 4 weeks after ablation, and corneal cryosections were
      subjected to two-color immunofluorescence staining with antibodies to laminin-1
      and antibodies to connexin43 for gap junctions, desmoglein 1 or 2 (desmoglein 1 +
      2) for desmosomes, or E-cadherin for adherens junctions. Sections were also
      stained with antibodies to occludin for examination of tight junctions. RESULTS:
      Laminin-1 was detected in the basement membrane, connexin43 in the basal cell
      layer, desmoglein 1 + 2 in the wing cell layer, E-cadherin in all cell layers,
      and occludin in the wing and superficial cell layers of the intact corneal
      epithelium. Laminin-1 immunostaining was not detected at the leading edge of
      migrating epithelial cells until 24 hours after ablation. Expression of
      connexin43 and desmoglein 1 + 2 coincided with the reappearance of laminin-1,
      whereas that of E-cadherin and occludin was apparent regardless of the absence or
      presence of laminin-1. Epithelial remodeling was complete after 4 weeks. The
      basement membrane was re-established, and the expression patterns for all the
      adhesion proteins were identical with those characteristic of the intact cornea.
      CONCLUSIONS: Actively migrating epithelial cells no longer manifested gap
      junctions and desmosomes in the wounded area with no basement membrane. Re
      establishment of the basement membrane coincided with reassembly of these
      intercellular junctions, suggesting that the presence of the basement membrane
      may be required for their reformation in the rat cornea.

PMID- 10937560
TI  - Corneal endothelial cell apoptosis in patients with Fuchs' dystrophy.
AB  - PURPOSE: To investigate whether apoptosis plays a notable role in degeneration of
      corneal endothelial cells in patients with Fuchs' dystrophy. METHODS: Forty-seven
      corneal buttons from 41 patients with Fuchs' dystrophy were studied. Nucleus
      labeling, transmission electron microscopy (TEM), and TdT-dUTP terminal nick-end
      labeling (TUNEL) were used to detect apoptosis. TEM and TUNEL were performed on
      sections of all 47 corneal buttons, and nucleus labeling was performed on the
      last 10 corneas. Seven human donor corneas, two corneal buttons from two patients
      with keratoconus, and one corneal button from a patient with interstitial
      keratitis were used as negative controls for detection of apoptotic endothelial
      cells. Negative controls were studied by means of nucleus labeling, TUNEL, and
      TEM. RESULTS: In the nucleus labeling assay, the average percentage of apoptotic
      endothelial cells was 2.65% in the Fuchs' dystrophy group (n = 10) and 0.23% in
      the control group (n = 10; P = 0.0003). In the TUNEL assay, labeling of some
      endothelial cells was observed on 42 of 47 corneas in the Fuchs' dystrophy group,
      whereas it was absent on most specimens of the control group. In TEM, most
      endothelial cell nuclei had a normal appearance, and apoptotic endothelial cells
      featuring condensed nucleus and decreased cell size could be observed
      exceptionally. Some apoptotic cells were found in the basal epithelial cell layer
      by means of nucleus labeling, TUNEL, and TEM in the Fuchs' dystrophy group but
      not in the control group. CONCLUSIONS: This study suggests that apoptosis plays
      an important role in endothelial cell degeneration in Fuchs' dystrophy. Because
      of a lack of conclusive evidence of increased endothelial apoptosis by TEM,
      further studies are needed to ascertain this finding.

PMID- 10937561
TI  - Cultivation of corneal epithelial cells on intact and denuded human amniotic
      membrane.
AB  - PURPOSE: Surgery to reconstruct the ocular surface is greatly facilitated by the
      use of amniotic membrane, either as a biologic drape or, more recently, as a
      substrate for the transplantation of cultivated corneal epithelial cells. This
      study was designed to compare the usefulness of intact and denuded human amniotic
      membranes as a substrate for corneal epithelial cell culture. METHODS: Small (3
      mm-diameter) biopsy specimens of superficial cornea including epithelium were
      excised from the central and limbal regions in rabbits. They were cultured on
      human amniotic membrane with or without amniotic epithelial cells and examined by
      light, scanning electron, and transmission electron microscopy. RESULTS: Cellular
      outgrowth from the central explants (n = 10) after 14 days in culture measured
      1.82 +/- 2.62 mm2 on intact amniotic membrane and 131.83 +/- 28.31 mm2 on denuded
      amniotic membrane. In contrast, outgrowths from the limbal explants (n = 10) at
      the same time measured 4.58 +/- 4.56 and 505.39 +/- 134.20 mm2 on intact and
      denuded amniotic membranes, respectively. The leading edges of the outgrowths on
      intact amniotic membrane were much less uniform than those on denuded amniotic
      membrane, and, in the former, corneal epithelial cells appeared to migrate over
      the top of amniotic epithelial cells. Limbal cells cultivated on denuded amniotic
      membrane formed a nicely stratified layer that adhered well to the underlying
      amniotic membrane. CONCLUSIONS: Denuded amniotic membrane appears to be an
      excellent substrate for the cultivation of corneal epithelial cells, with a view
      to transplantation.

PMID- 10937562
TI  - Expression of vascular endothelial growth factor and its receptors in inflamed
      and vascularized human corneas.
AB  - PURPOSE: To help further define the possible role of vascular endothelial growth
      factor (VEGF) in the pathogenesis of corneal neovascularization, the expression
      of VEGF and of its receptors Flt-1 and Flk-1 was investigated in various
      inflammatory corneal diseases. METHODS: Polyclonal antibodies to VEGF and its
      receptors were used for immunohistochemical staining of frozen sections of 38
      human corneas with various degrees of neovascularization and inflammation. In
      addition, a panel of monoclonal antibodies was used to characterize the
      composition of the inflammatory infiltrates and to confirm the presence of
      neovascularization. Furthermore, VEGF concentrations were determined in
      vascularized corneas using a sensitive enzyme-linked immunosorbent assay.
      RESULTS: VEGF was expressed by epithelial cells, by corneal endothelial cells, by
      vascular endothelial cells of limbal vessels and of newly formed vessels in the
      stroma, and weakly by keratocytes. Furthermore, VEGF expression was often
      markedly increased in inflamed corneas on epithelial cells and on vascular
      endothelial cells, particularly in the vicinity of macrophage infiltrates, and on
      fibroblasts in scar tissue. Correspondingly, VEGF concentrations were
      significantly higher in vascularized corneas compared with normal control corneas
      (P < 0.001). Expression of both VEGF receptors, Flt-1 and Flk-1, was increased on
      endothelial cells of newly formed vessels in the stroma of inflamed corneas
      compared with limbal vessels of normal control corneas. In addition, Flt-1 was
      also expressed by corneal endothelial cells and by macrophages, whereas Flk-1
      expression was lacking. CONCLUSIONS: These results demonstrate that VEGF, Flt-1,
      and Flk-1 are strongly expressed in inflamed and vascularized human corneas and,
      thus, may play an important role in corneal neovascularization.

PMID- 10937563
TI  - Anomalous acute inflammatory response in rabbit corneal stroma.
AB  - PURPOSE: To investigate the nature and cause of an acute, anomalous stromal edema
      after epithelial debridement in the rabbit cornea. METHODS: Series I: Adult New
      Zealand White rabbit corneas were mounted in perfusion chambers. The endothelium
      was bathed with Ringer's fluid, and the outer surface was covered with silicone
      oil. The epithelium of one eye was debrided with a scalpel before mounting, and
      the cornea of the fellow eye was debrided with a rotating brush after
      stabilization in the perfusion chamber. Using specular microscope tracking
      software, it was possible to measure total swelling and local swelling within the
      cornea. Series II: Diclofenac sodium ophthalmic solution 0.1% or a placebo was
      applied topically, 1 drop per 45 minutes for 3 hours before animals were
      euthanatized. RESULTS: Series I: Corneas with their epithelium scraped with a
      scalpel before mounting were 37.5 +/- 17.5 microm (n = 6; P < 0.001) thicker in
      vitro than the stromas of perfused, intact fellow corneas. Epithelial debridement
      with a rotating brush after mounting resulted in an immediate (within 8 minutes)
      stromal swelling that plateaued in 1 hour at 31.0 +/- 5.3 microm (n = 6; P <
      0.001). Curiously, in six of six corneas, the anterior stroma swelled more than
      the posterior stroma. In four of six corneas, the posterior stroma thinned.
      Analysis showed this pattern to be consistent with a sudden increase in anterior
      swelling pressure or osmotic pressure and to be inconsistent with a change in
      endothelial transport properties. Series II: Placebo-treated corneas swelled 30.6
      +/- 7.7 microm (n = 5) 1 hour after debridement, whereas corneas pretreated with
      diclofenac sodium swelled only 19.2 +/- 3.1 microm (n = 6; P < 0.008).
      CONCLUSIONS: The anterior stromal swelling occurs rapidly and near the site of
      epithelial injury suggesting messenger and/or enzymatic involvement with an
      effect parallel to apoptosis. Reduction of the swelling response with
      nonsteroidal anti-inflammatory drugs (NSAIDs) implicates the cyclooxygenase
      pathway. The swelling is similar to the unexplained acute edema that occurs
      during inflammation in the rat paw edema model, and may represent a general
      mechanism for mobilization of inflammatory cells.

PMID- 10937564
TI  - Fas- and interferon gamma-induced apoptosis in Chang conjunctival cells: further
      investigations.
AB  - PURPOSE: Previously interferon (IFN)gamma-induced apoptosis and expression of
      inflammation-related proteins in a human conjunctival cell line were
      demonstrated. The aim of this study was to further investigate the mechanisms of
      IFNgamma-, Fas-, and cycloheximide (CHX)-induced programmed cell death, with
      special attention to the role of transcriptional factors NF-kappaB and STAT1.
      METHODS: In a human conjunctival cell line (Chang conjunctival cells) apoptosis
      was induced with 500 ng/ml anti-Fas antibody (anti-Fas ab) alone (24 or 48 hours)
      or, as previously reported, with 300 U/ml of human recombinant IFNgamma alone (48
      hours). To study the role of IFNgamma on Fas-induced apoptosis, cells were
      treated first with IFNgamma at 30 U/ml during 24 hours (nontoxic dose), and then
      anti-Fas ab was applied for 24 hours. Moreover, to study the influence of CHX on
      Fas- and IFNgamma-induced apoptosis, cells were treated for 24 hours with 300
      U/ml IFNgamma together with a nontoxic concentration (1 microg/ml) of CHX, or
      with 500 ng/ml anti-Fas ab together with 1 microg/ml CHX (24 hours). After
      treatment, cell viability (neutral red assay), mitochondrial membrane potential
      (rhodamine 123 assay), chromatin condensation (Hoechst 33342 assay), and the
      index Hoechst/neutral red were studied by cold light microplate cytometry. The
      apoptotic process was sought for by contrast phase microscopy and DAPI staining
      and was confirmed by immunoblotting of PARP. Activation of caspase-3 (CPP32) and
      caspase-8 were investigated by Western blot analysis. NF-kappaB and STAT DNA
      binding activities were studied by electrophoretic mobility shift assays (EMSA).
      RESULTS: After 24 and 48 hours of treatment with anti-Fas ab alone, 15% to 20%
      and 30%, respectively, of apoptotic cells were observed. When anti-Fas sera were
      applied after IFNgamma pretreatment or together with CHX, 50% to 80% of cells
      demonstrated morphologic characteristics of programmed cell death. Apoptosis was
      confirmed by a cleavage of PARP and CPP32, by caspase-8 activation, and by an
      index Hoechst/neutral red greater than one. All these modifications were preceded
      by a decrease in mitochondrial membrane potential. EMSA revealed that NF-kappaB
      was activated after IFNgamma and anti-Fas ab treatments and inhibited after CHX
      treatment. STAT1 was strongly activated after IFNgamma treatment and only in a
      minor degree after anti-Fas ab treatment. STAT1-binding activity persisted after
      CHX treatment. CONCLUSIONS: The relative resistance of Chang cells toward Fas
      induced apoptosis could be related to the activation of NF-kappaB. IFNgamma
      induced programmed cell death preferentially involves the activation of STAT1
      that counterbalances NF-kappaB antiapoptotic effects. In fact, Fas-induced
      apoptosis was potentiated by IFNgamma or CHX treatments. These results suggest
      that NF-kappaB activation could maintain cell viability as well as participate in
      IFNgamma-induced inflammatory modifications, whereas STAT1 activation could
      provide, in this model, a proapoptotic signal.

PMID- 10937565
TI  - Doxycycline inhibition of interleukin-1 in the corneal epithelium.
AB  - PURPOSE: To evaluate the effect of doxycycline on the regulation of interleukin
      (IL)-1 expression and activity in human cultured corneal epithelium. METHODS:
      Human corneal limbal epithelium (HLE) was cultured from explants prepared from
      limbal rings of donor corneas. Primary cultured limbal epithelial cells were
      treated with either 10 microg/ml lipopolysaccharide (LPS), LPS with 10 microg/ml
      doxycycline, or LPS with 0.1 mg/ml methylprednisolone (MP) for 24 hours. The
      intracellular and supernatant protein amounts of IL-1alpha, the precursor and
      mature forms of IL-1beta, IL-1 receptor antagonist (IL-1 RA), and the
      intracellular level of IL-1beta-converting enzyme (ICE) were measured with enzyme
      linked immunosorbent assays (ELISAs). Western blot analysis was performed to
      evaluate IL-1 RA protein. mRNA steady state amounts were determined by RNase
      protection assay (RPA) for IL-1alpha, IL-1beta, IL-1 RA, and ICE. RESULTS: LPS
      increased the mRNA and protein amounts of intracellular and released IL-1alpha,
      mature IL-1beta, and IL-1 RA. Doxycycline inhibited the LPS-induced IL-1beta
      increase in the mRNA and protein amounts in the corneal epithelium and
      upregulated the expression of the anti-inflammatory IL-1 RA protein. In addition,
      doxycycline reduced the steady state level of the cellular ICE protein but did
      not affect the level of ICE transcripts. IL-1beta secreted to the conditioned
      media of HLE was functionally active in inducing matrix metalloproteinase (MMP)-1
      and MMP-3 in cultured corneal fibroblasts. Doxycycline significantly decreased IL
      1beta bioactivity in the supernatants from LPS-treated corneal epithelial
      cultures. These effects were comparable to those induced by the corticosteroid,
      MP. CONCLUSIONS: Doxycycline can suppress the steady state amounts of mRNA and
      protein of IL-beta and decrease the bioactivity of this major inflammatory
      cytokine. These data may partially explain the clinically observed anti
      inflammatory properties of doxycycline. The observation that doxycycline was
      equally potent as a corticosteroid, combined with the relative absence of adverse
      effects, makes it a potent drug for a wide spectrum of ocular surface
      inflammatory diseases.

PMID- 10937566
TI  - Frequency doubling perimetry in resolved optic neuritis.
AB  - PURPOSE: To study the visual field with frequency doubling technology (FDT) in
      patients with recovered optic neuritis and to detect loss of magnocellular
      projecting cells (M cells) in the extrafovea. METHODS: Fourteen patients who had
      undergone one attack of optic neuritis and recovered normal vision (1.0 or
      better) and critical fusion frequency were examined with conventional Humphrey
      automated perimetry central 30-2 and FDT c-20 threshold tests. After 1 year, 12
      patients were reexamined with central 30-2 and FDT c-20 tests. The visual fields
      examined by both perimeters were divided into three zones. The mean sensitivity
      in each zone in involved eyes, uninvolved eyes, and involved eyes after 1 year
      was compared with that in healthy eyes. RESULTS: Conventional automated perimetry
      showed depression toward the fovea. However, FDT demonstrated general depression,
      especially midperipheral deficits. After 1 year, the midperipheral deficits with
      frequency doubling perimetry (FDP) improved, as did central depression, as
      observed with central 30-2 tests. CONCLUSIONS: FDT was developed to detect early
      glaucomatous damage, which was thought to be caused by a loss of M cells. Our
      study suggested that patients with resolved optic neuritis also had a loss of M
      cell function in the extrafoveal area, as observed by field damage and its
      recovery.

PMID- 10937567
TI  - Modification of visually guided saccades by a nonvisual afferent feedback signal.
AB  - PURPOSE: To investigate the role of extraocular muscle afferent signals in the
      control of saccadic eye movements. METHODS: A suction scleral contact lens was
      used to impede the movements of the right eye while subjects executed visually
      guided saccades to briefly presented targets. Movements of the left eye were
      measured using infrared oculography. Saccade amplitude, peak velocity, and
      duration were analyzed trial by trial and compared before, during, and after the
      right eye was impeded. RESULTS: When the right eye was impeded, the amplitudes of
      saccades executed by the left eye were reduced. There was no alteration in the
      main sequence relationships. The amplitude effect had a rapid onset and offset.
      There was no evidence that the effects built up over a number of trials, nor was
      there evidence that individual saccades were modified on-line. CONCLUSIONS: These
      results are consistent with the hypothesis that extraocular muscle afferent
      signals provide a feedback signal of the movements of the eyes that is used to
      produce rapid adjustments of oculomotor output when required.

PMID- 10937568
TI  - Effect of timolol, latanoprost, and dorzolamide on circadian IOP in glaucoma or
      ocular hypertension.
AB  - PURPOSE: To compare the around-the-clock intraocular pressure (IOP) reduction
      induced by timolol 0.5%, latanoprost 0.005%, and dorzolamide in patients with
      primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: In this
      crossover trial, 20 patients with POAG (n = 10) or OHT (n = 10) were treated with
      timolol, latanoprost, and dorzolamide for 1 month. The treatment sequence was
      randomized. All patients underwent measurements for four 24-hour tonometric
      curves: at baseline and after each 1-month period of treatment. The patients were
      admitted to the hospital, and IOP was measured by two well-trained evaluators
      masked to treatment assignment. Measurements were taken at 3, 6, and 9 AM and
      noon and at 3, 6, and 9 PM and midnight by handheld electronic tonometer (TonoPen
      XL; Bio-Rad, Glendale, CA) with the patient supine and sitting, and a Goldmann
      applanation tonometer (Haag-Streit, Bern, Switzerland) with the patient sitting
      at the slit lamp. Systemic blood pressure was recorded at the same times. The
      between-group differences were tested for significance by means of parametric
      analysis of variance. The circadian IOP curve of a small group of untreated
      healthy young subjects was also recorded using the same procedures. To compare
      the circadian IOP rhythms in the POAG-OHT and control groups, the acrophases for
      each subject were calculated. RESULTS: When Goldmann sitting values were
      considered, all the drugs significantly reduced IOP in comparison with baseline
      at all times, except for timolol at 3 AM. Latanoprost was more effective in
      lowering IOP than timolol at 3, 6, and 9 AM (P = 0.03), noon (P = 0.01), 9 PM,
      and midnight (P = 0.05) and was more effective than dorzolamide at 9 AM, noon (P
      = 0.03), and 3 and 6 PM (P = 0.04). Timolol was more effective than dorzolamide
      at 3 PM (P = 0.05), whereas dorzolamide performed better than timolol at midnight
      and 3 AM (P = 0.05). An ancillary finding of this study was that in the group of
      healthy subjects, the pattern of IOP curve was different that in patients with
      eye disease. CONCLUSIONS: Latanoprost seemed to lead to a fairly uniform
      circadian reduction in IOP, whereas timolol seemed to be less effective during
      the nighttime hours. Dorzolamide was less effective than latanoprost but led to a
      significant reduction in nocturnal IOP. The reason for the difference in the
      pattern of the IOP curve of healthy subjects is currently unknown and deserves
      further investigation.

PMID- 10937569
TI  - The role of NaKCl cotransport in blood-to-aqueous chloride fluxes across rabbit
      ciliary epithelium.
AB  - PURPOSE: To evaluate the role of NaKCl cotransport in short-circuit current (Isc)
      and chloride fluxes across rabbit ciliary epithelium mounted in a Ussing-type
      chamber. METHODS: Bilayered intact ciliary epithelium free of stroma was obtained
      after perfusion and dissection of rabbit eyes and mounted in an Ussing-type
      chamber. The effects of bumetanide and other drugs on Isc and transepithelial
      36Cl fluxes in bicarbonate-containing Ringer's were determined. Immunoblot
      analysis was performed by standard techniques. RESULTS: Bumetanide (100 microM)
      applied to the blood (pigmented epithelium [PE]) side of the ciliary bilayer
      caused a dose-dependent decrease in Isc from 18.2 +/- 2.2 to 10.4 +/- 1.4
      microA/cm2 (43%). Bumetanide applied to the aqueous (nonpigmented epithelium
      [NPE]) side of the tissue inhibited Isc by only 12%. Immunoblots of dissected NPE
      and PE tissue probed with an antibody to mammalian NaKCl cotransporter detected
      approximately 10 times more NaKCl cotransporter protein in PE than in NPE. 36Cl
      flux studies revealed a PE-to-NPE chloride flux of 180.3 +/- 37.2 microEq/cm2 per
      hour and an NPE-to-PE flux of 72.3 +/- 22.9 microEq/cm2 per hour, indicating a
      net PE-to-NPE flux of 108.0 +/- 31.3 microEq/cm2 per hour across rabbit ciliary
      epithelium. Bumetanide inhibited the PE-to-NPE chloride flux by 52% but did not
      inhibit the NPE-to-PE flux. Isoproterenol (10 microM) added to the PE side of the
      bilayer increased Isc by a dose-dependent 53%. Prior addition of bumetanide to
      the PE side blocked the increase due to isoproterenol by 37%. Isoproterenol (10
      microM) stimulated the PE-to-NPE chloride flux by 75% but had no stimulatory
      effect on the NPE-to-PE chloride flux. 4,4'Diisothiocyanatostilbene
      2,2'disulfonic acid (DIDS) inhibited Isc when added to either side of the bilayer
      but was more potent at low concentrations (<100 microM) when added to the NPE
      side and more potent at higher concentrations (>100 microM) when added to the PE
      side. Prior addition of 1 mM DIDS to the NPE side decreased isoproterenol
      stimulation of Isc by 56%. CONCLUSIONS: NaKCl cotransporters located primarily on
      the blood side of rabbit ciliary epithelium contribute to aqueous-negative Isc
      and to blood-to-aqueous chloride transport across the tissue in bicarbonate
      containing medium. DIDS-inhibitable mechanisms, possibly including HCO3-Cl
      exchange and Cl channels, also play a role. Isoproterenol stimulation of Isc
      involves coordinate upregulation of PE-side NaKCl cotransport and an NPE-side
      DIDS-inhibitable mechanism(s).

PMID- 10937570
TI  - IgA antibodies to Toxoplasma gondii in human tears.
AB  - PURPOSE: To investigate whether mucosal immune responses directed against the
      ubiquitous parasite Toxoplasma gondii can be detected in tears of healthy humans.
      METHODS: Nonstimulated tears and blood were obtained from 62 healthy humans (mean
      age, 35 +/- 10 [SD] years). Serum anti-T. gondii immunoglobulin titers were
      determined by Sabin-Feldman (SF) dye test. Western blot analysis was used to
      compare the anti-T. gondii repertoire in tears and serum, and antibody avidity
      was determined by urea elution. Diluted tear and serum samples were incubated
      with the intact parasite to determine whether the antibodies found in tears and
      serum are capable of binding to surface exposed antigens of T. gondii. RESULTS:
      Eighty-one percent of the individuals tested had an anti-T. gondii IgA response
      in their tears, whereas only 23% had evidence of systemic immunity against the
      parasite. There was no apparent relation between chronic infection and presence
      of anti-T. gondii IgA in tears. Characteristically, the antigens recognized by
      the IgA antibodies in tears were often limited to at least one of four antigens
      with molecular weights of 74, 70, 49, and 34 kDa. The avidity of the anti-T.
      gondii IgA antibodies in tears was similar to the avidity of serum IgG
      antibodies. IgA antibodies directed against the 49- and 74-kDa antigens
      recognized epitopes exposed on the surface of the parasite. CONCLUSIONS: A major
      finding of this study is that tears of many individuals, chronically infected or
      not, contain IgA antibodies against T. gondii. It is not known whether these
      frequently observed antibody responses are the result of common mucosal immune
      responses against T. gondii or represent the natural antibody repertoire.

PMID- 10937572
TI  - Neuronal propagation of HSV1 from the oral mucosa to the eye.
AB  - PURPOSE: To identify possible neuronal pathways leading to herpetic ocular
      disease after primary oral infection in mice. METHODS: The SC16 strain of herpes
      simplex virus (HSV)-1 (10(6) plaque-forming units) was injected into the
      mucocutaneous border of the left upper lip. Animals were killed 2 to 10 days
      postinoculation (DPI). Spread of the virus in neural structures was studied by
      immunochemistry. RESULTS: HSV1 first replicated at the site of inoculation and
      then at the superior cervical ganglion (at 2 DPI). The trigeminal ganglion and
      the facial nerve fibers were infected by 4 DPI. Infection of the ciliary body and
      iris occurred at 6 DPI, together with several brain stem nuclei belonging to the
      autonomic or sensory pathways. Between 8 and 10 DPI, the neural infection
      gradually cleared up, except for the ipsilateral sympathetic ganglion, and
      ipsilateral keratitis appeared in some animals. CONCLUSIONS: The pattern of viral
      dissemination in this mouse model suggests that infection of iris and ciliary
      body results from transfer of virus in the superior cervical ganglion from
      sympathetic neurons innervating the lip to neighboring neurons innervating the
      anterior uvea. Later, zosteriform spread of virus from the trigeminal system may
      have contributed to the clinical and histologic findings.

PMID- 10937571
TI  - IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin
      induced uveitis.
AB  - PURPOSE: To determine the immunosuppressive status of aqueous humor (AqH) from
      mouse eyes afflicted with endotoxin-induced uveitis (EIU) and to identify the
      relevant cytokines responsible for immunomodulatory activity within EIU AqH.
      METHODS: Bacterial lipopolysaccharide (LPS) was injected into hind footpads of
      C3H/HeN mice; and AqH, collected at 6, 12, 24, and 48 hours, was evaluated for
      content of transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)
      alpha, interleukin (IL)-1beta, IL-6, and interferon (IFN)-gamma and capacity to
      suppress anti-CD3-driven T-cell proliferation. Cytokine mRNA expression in iris
      ciliary body (I/CB) was analyzed by RNase protection assays. RESULTS: During 6 to
      24 hours after LPS injection, total TGF-beta levels in AqH increased even though
      the fluid lost its capacity to suppress T-cell activation. At this time, AqH
      contained high levels of IL-6, and I/CB contained high levels of IL-6 mRNA. When
      IL-6 was neutralized with specific antibodies, inflamed AqH reacquired its
      capacity to suppress T-cell activation, which correlated with high levels of TGF
      beta. Coinjection of IL-6 plus antigen into the anterior chamber of the eye of
      normal mice prevented antigen-specific anterior chamber-associated immune
      deviation (ACAID). CONCLUSIONS: LPS-induced intraocular inflammation is
      associated with local production of IL-6, which robs AqH of its immunosuppressive
      activity, perhaps by antagonizing TGF-beta. The fact that IL-6 antagonized ACAID
      induction in normal eyes suggests that strategies to suppress the intraocular
      synthesis of IL-6 may reduce inflammation and restore ocular immune privilege.

PMID- 10937573
TI  - Herpes simplex virus-specific T cells infiltrate the cornea of patients with
      herpetic stromal keratitis: no evidence for autoreactive T cells.
AB  - PURPOSE: Herpetic stromal keratitis (HSK) is a T-cell-mediated inflammatory
      disease initiated by a herpes simplex virus (HSV) infection of the cornea.
      Recently, studies in the HSK mouse model have shown that the immunopathogenic T
      cells are directed against the HSV protein UL6 cross-reacting with an unknown
      corneal autoantigen. Whether this type of autoimmunity plays a role in human HSK
      was analyzed. METHODS: T-cell lines (TCLs) were generated from corneal buttons of
      12 patients with different clinical stages of HSV-induced necrotizing stromal
      keratitis (n = 9) or immune stromal keratitis (n = 3). The initiating virus was
      identified by polymerase chain reaction and immunohistology performed on the
      corneal buttons. Peripheral blood mononuclear cells (PBMCs) were isolated, and B
      cell lines (BLCLs) were generated by transformation with Epstein-Barr virus.
      Proliferative responses of these intracorneal TCLs were determined by culturing T
      cells with autologous BLCLs infected with HSV-1, HSV-2, wild-type vaccinia virus
      (VV-WT), or VV expressing HSV-1 UL6 (rVV-UL6). Alternatively, T cells were
      incubated with PBMCs pulsed with human cornea protein extract. RESULTS:
      Irrespective of clinical diagnosis or treatment, T cells were recovered from the
      corneal buttons of all the 12 HSK patients. The intracorneal TCLs of 9 of the 12
      HSK patients showed HSV-specific T-cell reactivity. In none of the TCLs, T-cell
      reactivity against HSV-1 UL6 or human corneal antigens was detected. CONCLUSIONS:
      These data suggest that the potentially immunopathogenic intracorneal T-cell
      response in HSK patients is directed to the initiating virus and not to a human
      corneal autoantigen or HSV-1 UL6.

PMID- 10937574
TI  - IFN-gamma and LPS-mediated IL-10-dependent suppression of retinal microglial
      activation.
AB  - PURPOSE: Human retinal microglia (MG) express constitutively major
      histocompatability complex (MHC) class II molecules and have thus been
      highlighted as potential immunocompetent antigen-presenting cells (APCs). This
      study was undertaken to characterize microglial expression of coaccessory
      molecules and the functional changes in antigen expression, cytokine production,
      migration, and phagocytosis after proinflammatory stimulation. METHODS: Fresh
      donor retinal MG were obtained and isolated using a percoll density gradient
      technique. Phenotypic characteristics used for isolating rodent microglia were
      applied and modified. Coaccessory molecule expression and intracellular cytokine
      production were assessed using three-color flow cytometric analysis in both
      freshly isolated and interferon (IFN)gamma-lipopolysaccharide (LPS)-stimulated
      MG. Using five-millimeter retinal explants in culture, microglial migratory
      behavior, changes in cell surface antigen expression and phagocytic activity were
      documented. RESULTS: MG could be clearly defined by the flow cytometric phenotype
      CD45low CD11b+ MHC class II+ CD86low CD40low. Freshly isolated MG showed mannose
      receptor-mediated uptake of dextran-FITC. MG migrated from explants, were
      adherent, and upregulated MHC class II expression. After IFNgamma-LPS stimulation
      of single-cell suspension of MG isolates, MHC class II expression was reduced,
      with an increase occurring in MG intracellular interleukin (IL)-10 and IL-10
      production. Microglial migration from explants was reduced after IFNgamma-LPS
      stimulation. CONCLUSIONS: These results highlight both phenotypic and behavioral
      characteristics that support an antigen-processing and -presenting capability of
      freshly isolated MG. However, proinflammatory stimulation with IFNgamma-LPS
      induces an IL-10-mediated downregulation of cell surface antigen expression and
      loss of migratory and phagocytic activity. Therefore, although equipped to act as
      APCs, MG are able to rapidly modulate their own function and behavior and as a
      result may have the potential to limit inflammation.

PMID- 10937575
TI  - Caspase and proteasome activity during staurosporin-induced apoptosis in lens
      epithelial cells.
AB  - PURPOSE: To determine what caspases are activated during staurosporin-induced
      apoptosis in cultured bovine lens epithelial cells (BLECs), to study the time
      course of caspase activation in relation to morphologic changes, and to
      investigate the effect of caspase and/or proteasome inhibition on apoptosis.
      METHODS: BLECs were incubated with staurosporin at different concentrations or
      for different times. Phosphatidylserine (PS) externalization was detected by
      annexin-V labeling, nuclear morphology was studied by staining with Hoechst 33342
      stain (Hoechst, Frankfurt, Germany), and the percentage of apoptotic cells was
      determined by the TdT-dUTP terminal nick-end labeling (TUNEL) assay. The activity
      of caspase-1, -2, -3, -4, -8, and -9 as well as the chymotrypsin-like activity of
      the proteasome was measured by the use of fluorogenic peptide substrates.
      Inhibition of the proteasome was performed by incubation with 10 microM
      lactacystin, and caspases were inhibited by 1 microM Z-DEVD-FMK or 20 microM Z
      VAD-FMK. RESULTS: Staurosporin treatment caused a dose- and time-dependent
      increase in the number of apoptotic cells and in caspase-3 activity. Activation
      of caspase-2, -4, -8, and -9 was also seen. Caspase activity was increased after
      3 hours' incubation with 1 microM staurosporin, which is also the time when most
      cells became annexin-V-positive. Nuclear changes indicative of apoptosis, viewed
      with both Hoechst and TUNEL staining, appeared after 4 to 6 hours of staurosporin
      incubation. Incubation of BLECs with lactacystin caused reduction of proteasome
      activity and increased apoptosis, evidenced in both the TUNEL assay and caspase-3
      activation. Preincubation of lens epithelial cells with caspase inhibitors caused
      complete inhibition of lactacystin- or staurosporin-induced caspase-3 activation
      (Z-DEVD-FMK/Z-VAD-FMK) and also of caspase-2, -4, -8, and -9 (Z-VAD-FMK), but the
      reduction in TUNEL-positive cells was only partial. PS translocation and DNA
      fragmentation after staurosporin treatment occurred despite complete caspase
      blockade. CONCLUSIONS: Staurosporin-induced apoptosis in BLECs involves
      activation of several caspases. Inhibition of the proteasome causes caspase-3
      activation and apoptosis. Both staurosporin- and lactacystin-induced apoptosis
      can be executed in a caspase-independent manner. The present data are useful for
      understanding of proteolytic mechanisms during apoptosis in lens epithelial
      cells, which may be an important event in normal lens development as well as in
      some types of cataract.

PMID- 10937576
TI  - Characterization of muscarinic receptors in human lens cells by pharmacologic and
      molecular techniques.
AB  - PURPOSE: Activation of muscarinic receptors has been implicated in an increased
      risk of cataract after anticholinesterase treatment for glaucoma. The purpose of
      the present study was to determine the acetylcholine muscarinic receptor
      subtype(s) present in native human lens epithelial cells (NHLECs) and a human
      lens cell line, HLE-B3, and to compare the distribution in other ocular cells.
      METHODS: Human lens cells were perfused with artificial aqueous humor (35 degrees
      C) after fura-2 incorporation, and calcium levels were measured using a
      fluorometric single-cell digital imaging system. Acetylcholine was the primary
      muscarinic agonist, and the receptor subtypes were elucidated by determining the
      relative effectiveness of pirenzepine and AF-DX 384 in blocking the agonist
      induced response. The levels of expression of mRNA for the receptor subtypes M1
      through M5 were determined by quantitative reverse transcription-polymerase chain
      reaction (QRT-PCR) using a sequence detection system (ABI Prism 7700; Perkin
      Elmer, Foster City, CA). This was performed using total RNA extracted from native
      lens, retina, iris, and sclera and also cultured lens cells. RESULTS:
      Acetylcholine induced a similar concentration-dependent increase in peak
      amplitude cytosolic calcium in the range 100 nM to 100 microM in both native and
      HLE-B3 cells. However, the kinetics of the response waveforms to 30-second pulses
      of acetylcholine were different in the two cell types. At higher concentrations
      (> 1 microM), a second phase appeared in the HLE-B3 cells that was absent in the
      NHLEC response. The 50% inhibitory concentration (IC50) values for blockade of a
      1 microM acetylcholine response by pirenzepine and AF-DX 384 were 30 nM and 230
      nM, respectively, for NHLECs, and 300 nM and 92 nM, respectively, for HLE-B3
      cells. The QRT-PCR data showed that more than 90% of the total muscarinic
      receptor mRNA from NHLEC was of M1 origin. In the HLE-B3 cells, however, more
      than 95% of the mRNA was of M3 origin. mRNA for M3 was also in greatest abundance
      in other eye tissues, although there was a significant contribution from M1 in
      iris and sclera. CONCLUSIONS: Both NHLECs and HLE-B3 cells express muscarinic
      receptors that produce significant changes in cytosolic calcium in response to
      acetylcholine. Both pharmacologic and QRT-PCR evidence shows that whereas the M1
      subtype predominates in NHLECs, M3 is the major contributor in HLE-B3 cells. In
      all other eye tissues, M3 appears to be the major contributor. These data should
      be taken into account when choosing particular models to investigate cataract
      mechanisms and also when designing muscarinic agonists to treat glaucoma.

PMID- 10937577
TI  - An action spectrum for UV-B radiation and the rat lens.
AB  - PURPOSE: To determine an action spectrum for UV-B radiation and the rat lens and
      to show the effect of the atmosphere and the cornea on the action spectrum.
      METHODS: One eye of young female rats was exposed to 5-nm bandwidths of UV-B
      radiation (290, 295, 300, 305, 310, and 315 nm). Light scattering of exposed and
      nonexposed lenses was measured 1 week after irradiation. A quadratic polynomial
      was fit to the dose-response curve for each wave band. The dose at each wave band
      that produced a level of light scattering greater than 95% of the nonexposed
      lenses was defined as the maximum acceptable dose (MAD). Transmittance of the rat
      cornea was measured with a fiberoptic spectrophotometer. The times to be exposed
      to the MAD in Stockholm (59.3 degrees N) and La Palma (28 degrees N) were
      compared. RESULTS: Significant light scattering was detected after UV-B at 295,
      300, 305, 310, and 315 nm. The lens was most sensitive to UV-B at 300 nm.
      Correcting for corneal transmittance showed that the rat lens is at least as
      sensitive to UV radiation at 295 nm as at 300 nm. The times to be exposed to the
      MAD at each wave band were greater in Stockholm than in La Palma, and in both
      locations the theoretical time to be exposed to the MAD was least at 305 nm.
      CONCLUSIONS: After correcting for corneal transmittance, the biological
      sensitivity of the rat lens to UV-B is at least as great at 295 nm as at 300 nm.
      After correcting for transmittance by the atmosphere, UV-B at 305 nm is the most
      likely wave band to injure the rat lens in both Stockholm and La Palma.

PMID- 10937578
TI  - Heparin's roles in stabilizing, potentiating, and transporting LEDGF into the
      nucleus.
AB  - PURPOSE: Lens epithelium-derived growth factor (LEDGF) is a 60-kDa protein that
      dramatically enhances cellular survival, growth, adhesiveness, and resistance to
      heat and oxidative stress. Full-size recombinant LEDGF is degraded during
      prokaryotic preparation. Heparin's capacity to stabilize recombinant LEDGF in the
      face of various stresses (heat, pH, proteolysis), to potentiate its growth
      enhancing properties, and to enable transport of LEDGF into the nucleus of mouse
      lens epithelial cells has been characterized. METHODS: LEDGF-cDNA was cloned in a
      pGEX-2T expression vector to produce a fusion protein, GST-LEDGF. Porcine heparin
      was used to stabilize GST-LEDGF. Heparin-Sepharose was used to characterize
      heparin-GST-LEDGF binding, and GST-LEDGF or heparin-GST-LEDGF was used to
      quantitate heparin's stabilization of LEDGF in the face of heat, pH, and
      proteolytic stresses. Fluorescein isothiocyanate-labeled GST-LEDGF and heparin
      GST-LEDGF were incubated with cultured mouse lens epithelial cells (LECs).
      Fluorescence microscopy and immunostaining techniques were used to monitor
      heparin's potentiation of LEDGF's growth stimulation and heparin's role in the
      translocation of GST-LEDGF from the extracellular space into the cytoplasm and
      nucleus. RESULTS: Heparin, at concentrations as low as 7.1 mg/ml, protected GST
      LEDGF from degradation and increased the yield of the full-size fusion protein in
      a prokaryotic system. It also protected GST-LEDGF from heat, acid-base
      deactivation, and proteolytic degradation with trypsin and chymotrypsin and
      greatly potentiated LEDGF's enhancement of mouse LEC growth in culture. It also
      increased nuclear uptake of exogenous GST-LEDGF and endogenous LEDGF.
      CONCLUSIONS: Heparin protected GST-LEDGF from degradation under various stress
      conditions and facilitated transport of GST-LEDGF into the nucleus.

PMID- 10937579
TI  - Molecular cloning of ovine connexin44 and temporal expression of gap junction
      proteins in a lens cell culture.
AB  - PURPOSE: The lens plasma membranes of several mammalian species have been shown
      to contain three different connexin proteins. The goal of this study was to clone
      the sheep homologue of rat connexin46 identified as sheep connexin44 and to
      determine the temporal changes in the expression of the three sheep connexin
      proteins in a lens primary cell culture system. METHODS: A sheep genomic library
      was screened with a rat lens connexin46 cDNA probe. Lens junctional protein and
      mRNA levels were determined in a sheep primary cell culture system by Western and
      Northern blot analyses, respectively. RESULTS: Sheep connexin44, the homologue of
      rat lens connexin46, was identified as a single-copy gene with a predicted
      molecular weight of 43,989 Daltons that is contained within a single exon.
      Northern blot analysis detected a 2.2-kb connexin44 transcript in RNA isolated
      from lens but not that isolated from heart, kidney, liver, or lung. During the in
      vitro differentiation of lens epithelial cells from 5 to 20 days in culture,
      connexin43 mRNA levels declined approximately 75%, whereas connexin49 RNA levels
      increased approximately 24 fold. The 40% decrease in the level of connexin43
      protein and the 21-fold increase in the level of connexin49 protein did not
      directly correlate with the changes in mRNA levels encoding these proteins during
      this same period. Although detectable, the amount of connexin44 mRNA and protein
      remained low throughout the 20-day period during which lens cells were grown in
      culture. Neither mRNA nor protein encoding MP20 or MP26 transcripts could be
      detected in even the oldest 20-day lens cultures. CONCLUSIONS: Steady state mRNA
      levels of sheep connexin43 and connexin49 do not appear to be the only factor
      regulating the expression of these genes during in vitro differentiation of lens
      cells in culture. Although a decreased level of expression of connexin43 was
      accompanied by an increased level of expression of connexin49 over the 20-day
      period in culture, connexin44 mRNA and protein levels remained low throughout
      this 20-day period. Overall, these results suggest that these junctional proteins
      have a unique temporal pattern of expression during differentiation, and this
      lens primary cell culture system provides a valuable tool to better understand
      this process.

PMID- 10937580
TI  - A new locus for autosomal dominant cataract on chromosome 12q13.
AB  - PURPOSE: To map the gene for autosomal dominant cataracts (ADC) in an American
      white family of European descent. METHODS: Ophthalmic examinations and linkage
      analyses using a variety of polymorphisms were performed; two-point lod scores
      calculated. RESULTS: Affected individuals (14 studied) exhibited variable
      expressivity of embryonal nuclear opacities based on morphology, location within
      the lens, and density. This ADC locus to 12q13 was mapped on the basis of
      statistically significantly positive lod scores and no recombinations (theta(m) =
      theta(f) = 0) with markers D12S368, D12S270, D12S96, D12S359, D12S1586, D12S312,
      D12S1632, D12S90, and D12S83; assuming full penetrance, a maximum lod score of
      4.73 was calculated between the disease locus and D12S90. CONCLUSIONS: The
      disease in this family represents the first ADC locus on chromosome 12; major
      intrinsic protein of lens fiber (MIP) is a candidate gene.

PMID- 10937581
TI  - Coexistence of C-type natriuretic peptide and atrial natriuretic peptide systems
      in the bovine cornea.
AB  - PURPOSE: To determine whether the cornea synthesizes natriuretic peptides and
      contains their receptors. METHODS: The synthesis of the natriuretic peptides, C
      type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP), in the
      bovine cornea was determined by high-performance liquid chromatography (HPLC)
      with radioimmunoassay and Southern blot analysis. The presence of natriuretic
      peptide receptor (NPR)-A and -B and their localizations were measured by reverse
      transcription-polymerase chain reaction (RT-PCR), in vitro autoradiography, and
      the activation of particulate guanylyl cyclase by natriuretic peptides in the
      corneal membrane. RESULTS: The serial dilution curves of corneal extracts were
      parallel to the standard curves of CNP and ANP. With reversed-phase HPLC, a major
      immunoreactive peak of CNP or ANP was observed at the elution time corresponding
      with synthetic CNP(1-53) or atriopeptin III (APIII), respectively. The presence
      of mRNAs of CNP and ANP was also detected in the cornea by RT-PCR and/or Southern
      blot analysis. Production of 3',5'-cyclic guanosine monophosphate (cGMP) by the
      activation of particulate guanylyl cyclase in the corneal membrane was stimulated
      by ANP, BNP, and CNP. More cGMP was produced by CNP than by the other natriuretic
      peptides. Specific 125I-[Tyr0]-CNP(1-22) binding sites were localized in the
      endothelial cell layer of cornea. The apparent dissociation constant (Kd) value
      of the cornea was 3.06 +/- 0.73 nM and the maximum binding capacity was 3.40 +/-
      0.63 femtomoles/mm2. Both NPR-A and NPR-B mRNAs were detected by RT-PCR.
      CONCLUSIONS: The cornea synthesizes CNP and ANP and contains their receptors.
      These results suggest that the CNP and ANP systems coexist in the bovine cornea.

PMID- 10937582
TI  - Subfoveal choroidal blood flow in response to light-dark exposure.
AB  - PURPOSE: To document the response of subfoveal choroidal blood flow (ChBF) in the
      human eye induced by light and dark exposures and provide some insight into the
      mechanism underlying this response. METHODS: In a group of 12 volunteers (age, 25
      60 years), ChBF was measured with a confocal laser Doppler flowmeter. Wavelength
      of the probing laser beam was 785 nm (90 microW at the cornea). ChBF was recorded
      in room light, in darkness, in room light after dark adaptation, and during
      strong green light exposure after exposure to room light. After dark adaptation
      of both eyes, ChBF was also measured in one eye while only the fellow eye was
      exposed to strong visible light. RESULTS: Although ChBF was stable during room
      light condition, it decreased significantly by 15% (P < 0.01) during dark
      adaptation. After 6 minutes of room light following 20 minutes of darkness, ChBF
      was back to baseline. Strong, diffuse, green light exposure over a field of 40
      degrees, as well as the probing laser beam, had no detectable effect on ChBF. No
      change in ChBF was detected when the fellow eye was illuminated after both eyes
      had been dark adapted. CONCLUSIONS: The findings did not confirm the presence of
      an active process of ChBF regulation in response to light exposure in humans.
      They demonstrate, however, a reversible decrease in ChBF that occurs after a
      transition from room light to darkness, which could involve a neural mechanism.

PMID- 10937583
TI  - Sympathetic nervous system plays a role in postnatal eyeball enlargement in the
      rabbit.
AB  - PURPOSE: To examine the role of ocular sympathetic activity in the enlargement of
      the rabbit eyeball during postnatal growth. METHODS: Fourteen New Zealand albino
      rabbits aged 5 weeks underwent unilateral surgical transection of the cervical
      sympathetic trunk caudal to the superior cervical ganglion. Postoperative
      enlargement of both eyeballs was monitored by measuring the axial length and
      corneal diameters every 2 weeks for 22 weeks (7-27 weeks of age). Rabbits were
      housed under a 12-hour light/12-hour dark cycle, and the measurements were made
      in the middle of the light period. At a final age of 30 to 31 weeks, the
      refractive state of the whole eye was determined on both sides by measurement
      through the central cornea with a refractometer. Rabbits were then killed,
      eyeballs enucleated, and their ocular volumes determined. RESULTS: From 9 weeks
      of age the axial length and corneal diameters were significantly shorter (P <
      0.05) in the decentralized eye (surgical side) compared with the intact eye. This
      reduction remained statistically significant throughout the study period.
      However, the final refractive states of the two eyes were found not to be
      different. The mean ocular volume determined after postmortem enucleation was
      4.5% less in the decentralized eye than in the intact eye (P < 0.05).
      CONCLUSIONS: Sympathetic nervous system activity is involved in the normal
      enlargement of the rabbit eyeball during postnatal growth. However, removal of
      the ocular sympathetic tone at the age of 5 weeks does not significantly alter
      the refractive state of the eye when measured in young adulthood.

PMID- 10937584
TI  - Administration of 17beta-estradiol attenuates retinal ischemia-reperfusion injury
      in rats.
AB  - PURPOSE: Accumulating evidence has suggested that 17beta-estradiol exerts
      protective effects against ischemic damage in various organs. In addition,
      leukocytes that accumulate in postischemic tissues are thought to play a central
      role in ischemia-reperfusion injury. This study was designed to evaluate
      quantitatively the inhibitory effects of 17beta-estradiol on leukocyte
      accumulation during ischemia-reperfusion injury and on subsequent retinal damage
      after transient retinal ischemia. METHODS: Transient (60 minutes) retinal
      ischemia was induced in male rats by temporary ligation of the optic nerve.
      Thirty minutes before induction of ischemia, 17beta-estradiol (0.1 mg/kg) was
      administered intraperitoneally. At 6, 12, 24, and 48 hours after reperfusion,
      leukocyte accumulation in the retina was evaluated in vivo by means of acridine
      orange digital fluorography. Histologic and electroretinographic (ERG) studies
      were carried out to evaluate retinal damage. RESULTS: Treatment with 17beta
      estradiol significantly inhibited postischemic leukocyte accumulation; the
      maximum number of accumulating leukocytes was reduced by 35.7% at 24 hours after
      reperfusion (P = 0.01). Histologic examination showed that administration of
      17beta-estradiol significantly reduced retinal damage, which was most obvious in
      the inner retina, 168 hours after reperfusion (P = 0.0001). ERG studies at 12 and
      168 hours after reperfusion showed that recovery of the b-wave amplitude was
      significantly improved with treatment of 17beta-estradiol (P = 0.023).
      CONCLUSIONS: The present study demonstrated the inhibitory effects of 17beta
      estradiol on leukocyte accumulation and subsequent tissue injury during retinal
      ischemia-reperfusion injury.

PMID- 10937585
TI  - The effect of calcium channel blocker diltiazem on photoreceptor degeneration in
      the rhodopsin Pro213His rat.
AB  - PURPOSE: To determine whether the calcium channel blocker D-cis-diltiazem
      promotes photoreceptor survival in rats with the Pro23His rhodopsin mutation.
      METHODS: Heterozygous Pro23His rhodopsin line 1 rats (n = 11) were treated daily,
      according to a protocol applied successfully in rd mice, with D-cis-diltiazem
      hydrochloride increased incrementally from 21 to 54 mg/kg in a divided dose (8 AM
      and 8 PM) administered by intraperitoneal (i.p.) injection for 21 days, beginning
      on days of age 10 through 12. Saline-treated line 1 rats (n = 6) received i.p.
      injections of an equal volume of 0.9% saline. Analysis on day 35 of age included
      dark-adapted corneal electroretinogram (ERG) b- and a-waves recorded from
      threshold to 0.63 log candela-seconds [cd-s]/m2, saturated a-waves elicited with
      a 2.1 log cd-s/m2 flash, and morphometry of the outer nuclear layer (ONL) and rod
      outer segments (ROS). RESULTS: ONL width and cell counts of diltiazem-treated and
      saline-treated animals at 35 days were reduced to 64%-68% of 15-day-old untreated
      P23H line 1 retinas. No photoreceptor rescue was found by measuring ONL width (P
      = 0.84), cell count (P = 0.42), or ROS length (P = 0.85). Functional assays by
      ERG b-wave threshold (P = 0.57), b-wave maximum amplitude (P = 0.46), and
      saturated a-wave amplitude (P = 0.59) also showed no rescue. CONCLUSIONS: D-cis
      Diltiazem did not rescue photoreceptors of Pro23His rhodopsin mutation line 1
      rats treated according to the protocol used in rd mouse.

PMID- 10937586
TI  - PKC-beta inhibitor (LY333531) attenuates leukocyte entrapment in retinal
      microcirculation of diabetic rats.
AB  - PURPOSE: The activity of protein kinase C (PKC), preferentially beta isoform of
      PKC, has been shown to be elevated in the diabetic retina. Recently, LY333531, a
      specific inhibitor of PKC-beta, has been reported to improve the decrease of
      retinal blood flow in early diabetes. Increased leukocyte entrapment has been
      suggested to be involved in blood flow disturbances in the early diabetic retina.
      This study was designed quantitatively to evaluate leukocyte entrapment in the
      retinal microcirculation of diabetic rats and the effect of LY333531 on leukocyte
      entrapment. METHODS: Diabetes was induced in male Long-Evans rats by
      intraperitoneal injection of streptozotocin (60 mg/kg). LY333531 (0.1, 1.0, or
      10.0 mg/kg/d) was administered orally during a 4-week diabetic period. Leukocyte
      entrapment in the retinal microcirculation was quantitatively evaluated in vivo
      with acridine orange digital fluorography. RESULTS: The number of leukocytes
      trapped in the retinal microcirculation of diabetic rats (mean +/- SEM; 14.3 +/-
      1.3 cells/mm2) was significantly increased, compared with nondiabetic control
      rats (7.5 +/- 0.3 cells/mm2; P < 0.0001). Oral administration of LY333531
      significantly decreased the number of leukocytes trapped in the retinal
      microcirculation of diabetic rats (10.9 +/- 0.6, 11.3 +/- 0.7, and 10.4 +/- 0.4
      cells/mm2 with LY333531 0.1, 1.0, and 10.0 mg/kg/d, respectively; P < 0.05).
      CONCLUSIONS: Treatment with LY333531 attenuated the increase of leukocyte
      entrapment in the retinal microcirculation during the period of early diabetes.
      This effect may contribute to the improvement of abnormal retinal blood flow in
      early diabetes with LY333531. LY333531 might have a therapeutic efficacy in
      preventing microcirculatory flow disturbances by trapped leukocytes in the early
      diabetic retina.

PMID- 10937587
TI  - Synthesis of osteonectin by human retinal pigment epithelial cells is modulated
      by cell density.
AB  - PURPOSE: To determine whether human retinal pigment epithelial (HRPE) cells are
      able to synthesize the antiadhesive protein osteonectin, also known as secreted
      protein, acidic and rich in cysteine (SPARC). Additionally, because locally
      produced SPARC may modulate cellular behavior during tissue repair, to ascertain
      whether HRPE SPARC production and HRPE proliferation, migration, and/or
      differentiation are associated, in a simple HRPE wound-healing model. METHODS:
      Immunohistochemical and Western blot analyses of SPARC protein expression by low-
      and high-density cultured HRPE cells were undertaken. Total RNA extracted from
      cultures was studied by reverse transcription-polymerase chain reaction (RT-PCR)
      and Northern blot analysis. Western and Northern blot analyses were evaluated by
      densitometry. Experiments were repeated with HRPE cells cultured in the presence
      of 1, 10, or 100 microM of the differentiating agents butyric acid (BA) and
      retinoic acid (RA). RESULTS: HRPE cell cultures exhibited SPARC immunoreactivity.
      Western blot analysis of cell lysates and conditioned media showed a 43-kDa
      protein. RT-PCR and Northern blot analysis confirmed the presence of SPARC mRNA
      (with transcripts at 2.2 and 3.0 kb). Protein and mRNA transcript band
      densitometry revealed a higher proportion of SPARC protein and mRNA in high
      density HRPE cell culture than in low-density culture. Neither BA nor RA (at the
      concentrations assessed) had a significant effect on SPARC production by HRPE
      cells in high- or low-density culture. CONCLUSIONS: HRPE can synthesize SPARC.
      Although the findings do not support an invariable association between SPARC
      production by HRPE and HRPE proliferation, migration, or differentiation, they
      demonstrate that synthesis of SPARC by HRPE is modulated by cell density.

PMID- 10937588
TI  - X-linked retinitis pigmentosa: mutation spectrum of the RPGR and RP2 genes and
      correlation with visual function.
AB  - PURPOSE: To assess the frequency of RPGR and RP2 mutations in a set of 85
      patients with X-linked retinitis pigmentosa (XLRP) and to compare the visual
      function of patients with mutations in RPGR versus RP2. METHODS: Eighty-five
      unrelated patients with XLRP were ascertained, mainly from North America. The
      single-strand conformation polymorphism (SSCP) and a direct sequencing technique
      were used to screen their DNA for mutations in the coding region and splice sites
      of RPGR and RP2. The Snellen visual acuities, visual field areas, and 0.5-Hz and
      30-Hz electroretinograms (ERGs) were measured in male patients. The visual
      function parameters were compared using multiple regression analysis. RESULTS: A
      wide spectrum of mutations was found in both genes, including missense, nonsense,
      splice-site, and frameshift mutations. Twenty putative pathogenic mutations in
      RPGR, 15 of which were novel, were found in 22 patients (26%), whereas 6
      mutations in RP2, 4 of which were novel, were found in 6 patients (7%). A high
      fraction of the mutations in both genes affected amino acid residues within or
      adjacent to presumed functional domains. Comparison of visual function between
      comparably aged patients with mutations in RPGR versus RP2 showed that, on
      average, patients with RPGR mutations have lower ERG amplitudes and smaller
      visual field areas. CONCLUSIONS: Mutations in RPGR and RP2 genes together account
      for approximately 33% of cases of XLRP in North America. Patients with RPGR
      mutations have less overall retinal function on average than those with RP2
      mutations, on the basis of measurements of visual field areas and full-field ERG
      amplitudes.

PMID- 10937589
TI  - The human electro-oculogram: interaction of light and alcohol.
AB  - PURPOSE: To investigate the production of the voltage changes evoked in the
      retinal pigment epithelium (RPE) by light and alcohol and the interaction of
      these agents. METHODS: The eye movement potential in humans was intermittently
      recorded to standard horizontal excursions for long periods during which either
      retinal illumination was altered or ethyl alcohol was administered by the oral,
      intragastric, or intravenous route. In other experiments, both light and alcohol
      were administered. RESULTS: Alcohol and light produced near identical
      corneofundal voltage changes (positive and then negative) over more than 40
      minutes. Differences in timing between alcohol and light increases are explicable
      by the delays in alcohol absorption. Weak background light suppressed the effect
      of light steps, and low levels of background alcohol suppressed the response to
      subsequent doses. Backgrounds of one agent did not affect the voltage changes
      caused by the other. Minimal alcohol effects were seen after administration of 1
      g orally or 270 mg intravenously--that is, doses that produced undetectable
      changes in breath alcohol. The semisaturating oral dose was approximately 20
      mg/kg. CONCLUSIONS: Alcohol and light act through separate pathways to form a
      final common pathway inside the RPE cell that is responsible for triggering the
      timing of the slow oscillatory changes of EOG voltage. The sensitivity and
      duration with which alcohol affects the RPE are comparable with the effect of
      melatonin or dopamine, although only the former interacts with light similarly to
      alcohol. Transient modulation of the acetylcholine (Ach) neuronal receptor occurs
      at similar sensitivity, but all other known actions of alcohol require higher
      concentrations than this RPE action.

PMID- 10937590
TI  - The electro-oculographic responses to alcohol and light in a series of patients
      with retinitis pigmentosa.
AB  - PURPOSE: Alcohol produces changes in the electro-oculogram (EOG) similar to those
      caused by light, but indirect evidence indicates that alcohol directly affects
      the retinal pigment epithelium (RPE). An investigation of the alcohol-induced
      increase (termed the alcohol rise in this study) in patients with disease of the
      photoreceptors was therefore of interest. METHODS: Standard EOGs were recorded
      after oral administration of alcohol in a group of patients with retinitis
      pigmentosa (RP). RESULTS: The average response of 17 patients to alcohol was a
      slow decrease of potential, which contrasts with the normal alcohol rise. In
      patients with considerable residual peripheral field, alcohol produced a small
      increase of voltage, followed by a prolonged decrease. The slower decrease in the
      EOG voltage was evident in patients with small fields and could be seen even in
      those who had lost all visual function. Light caused small increments of EOG
      voltage (termed light rises), again related to the field size. CONCLUSIONS: It is
      probable that the intracellular signaling system that causes the alcohol and
      light rises is lost in RP.

PMID- 10937591
TI  - Early-onset severe rod-cone dystrophy in young children with RPE65 mutations.
AB  - PURPOSE: To describe the ocular phenotype of patients with RPE65 mutations in
      infancy and young childhood. METHODS: Four children from three families with
      severe early-onset visual impairment related to electrophysiologically detectable
      retinal dystrophy were screened for mutations in the RPE65 gene. Visual function
      from infancy to the age of 10 years was assessed with age-adapted methods.
      Clinical examinations and electroretinograms (ERGs) were also performed on the
      six parents. RESULTS: In all three families, patients were compound heterozygous
      for mutations of the RPE65 gene (ins144T/IVS1+5G-->A, R91W/Y368H,
      1114delA+T457N/IVS1+5G-->A). Visual acuity was measurable in all patients at the
      age of 6 to 10 years, despite severe visual impairment noted during infancy and
      congenital nystagmus in three of the four patients. Photophobia was not a
      feature. Funduscopic changes were discrete, the most prominent finding being
      increased granularity in the macula and the periphery. Peripheral vision was well
      preserved, measured by Goldmann perimetry. Rod ERGs were not recordable, whereas
      cone ERGs were detectable in early childhood. All features taken together suggest
      a specific form of Leber congenital amaurosis (LCA) distinguishable on clinical
      grounds. ERGs were normal in five of the six parents. One father had an ERG
      compatible with congenital stationary night blindness unrelated to his
      heterozygous state for the RPE65 mutation. CONCLUSIONS: RPE65 mutations on both
      alleles may be associated with early-onset severe rod-cone dystrophy. Visual
      functions of the four patients were better than is usually seen in LCA, in
      particular in cases associated with retGC1 mutations. RPE65 mutations should be
      suspected in infants who appear to be blind in dim surroundings but react to
      objects in bright illumination and have nonrecordable rod ERGs and residual cone
      ERGs.

PMID- 10937592
TI  - Transient ischemic injury in the rat retina caused by thrombotic occlusion
      thrombolytic reperfusion.
AB  - PURPOSE: To establish a clinically relevant model of transient retinal ischemia
      by thrombotic occlusion-thrombolytic reperfusion of the central retinal artery of
      the rat. METHODS: Thrombus was photochemically induced in the central retinal
      artery by the combination of intravenous injection of photo-sensitive dye, rose
      bengal, and green laser irradiation focused on the artery. Transient retinal
      ischemia for 60 minutes was achieved by a subsequent systemic administration of
      tissue-type plasminogen activator to reperfuse the occluded vessel. Samples of
      retinas were excised from the animals killed 3, 9, 12, 24, 48, and 78 hours after
      the reperfusion. The experimental data were processed using the TdT-dUTP terminal
      nick-end labeling (TUNEL) method to detect apoptotic cells. RESULTS: The
      transient retinal ischemia caused time-sequential apoptotic changes in the
      retinal cells as evaluated by counting the number of TUNEL-positive cells. The
      most remarkable changes occurred in the central area of retina, and further on
      the sections taken 24 hours after reperfusion. The peripheral area was less
      affected, and the outer nuclear cell layer was almost unaffected throughout the
      observation period. CONCLUSIONS: The proposed method to cause retinal transient
      ischemia is highly reproducible, and it is easy to simulate the progress and
      topographical distribution of retinal changes observed in the clinical cases of
      central retinal arterial occlusion and its subsequent thrombolytic reperfusion.
      This may provide a useful tool for constructing the effective thrombolytic
      strategies against the central retinal arterial occlusion and for evaluating the
      effects of neuroprotective agents.

PMID- 10937594
TI  - c-Fos protein in photoreceptor cell death after photic injury in rats.
AB  - PURPOSE: To examine the involvement of c-Fos protein in light-induced
      photoreceptor cell death in rats. METHODS: Thirty-two Lewis albino rats were
      exposed to green fluorescent light (480-520 nm) of 300 to 320 foot-candles (3228
      3443.2 lux) for 3 hours, allowed to recover in the dark, and euthanatized at 0,
      1, 3, 6, 12, 24, or 96 hours after light exposure. c-Fos was detected
      immunohistochemically and nicked DNA by in situ TdT-dUTP terminal nick-end
      labeling (TUNEL). Double labeling of c-Fos and DNA nicks was also performed.
      RESULTS: There was a time-dependent change in the number of c-Fos-positive
      photoreceptor nuclei after light injury, which paralleled the change in the
      number of TUNEL-positive nuclei. The temporal and spatial appearance of these
      nuclei also matched the appearance of pyknotic nuclei of the outer nuclear layer.
      Double-labeling study revealed that some c-Fos-positive nuclei were also TUNEL
      positive nuclei. CONCLUSIONS: There was an acute accumulation of c-Fos protein in
      photoreceptors associated with cell death. This study further supports other
      studies showing that c-Fos is linked to apoptotic photoreceptor cell death.

PMID- 10937593
TI  - Upregulated expression of neurocan, a nervous tissue specific proteoglycan, in
      transient retinal ischemia.
AB  - PURPOSE: Neurocan, a nervous tissue-specific chondroitin sulfate proteoglycan
      synthesized primarily by neurons, is expressed abundantly in developing rat
      retina, whereas it is rarely expressed in adult rat retinas. This study
      investigated the reexpression of neurocan in a pathologic condition of adult rat
      retina. METHODS: Transient retinal ischemia was produced by occlusion of the
      retinal artery for 60 minutes. After transient retinal ischemia, neurocan
      expression was investigated by reverse transcription-initiated polymerase chain
      reaction (RT-PCR), immunohistochemistry, and immunoblot analysis. RESULTS:
      Semiquantitative analysis using RT-PCR revealed that mRNA expression for neurocan
      increased at 24 hours after reperfusion. Furthermore, on immunoblot analysis
      using an anti-neurocan antibody, MAb 1G2, the intensity of the 220-kDa band as
      well as the 150-kDa band increased markedly at 24 and 72 hours after reperfusion.
      The 220-kDa band was predominant at 24 hours after reperfusion, whereas the
      intensity of the 150-kDa band became almost the same as that of the 220-kDa band
      at 72 hours after reperfusion. Immunohistochemical analysis revealed that
      upregulated neurocan immunoreactivity was associated with glial Muller cells.
      CONCLUSIONS: Thus, upregulated expression of neurocan in transient retinal
      ischemia was demonstrated. Furthermore, the immunohistochemical analysis revealed
      that the upregulated expression of neurocan is derived from Muller cells,
      although it has been thought that neurocan is synthesized by neurons so far. The
      neurocan expression by Muller cells suggests that this proteoglycan plays a role
      in the damage and repair processes in diseased retina.

PMID- 10937595
TI  - Isolation and characterization of mucinlike glycoprotein associated with
      photoreceptor cells.
AB  - PURPOSE: Although previous lectin-histochemical studies have shown that O-linked
      glycoproteins are distributed in cone pedicles and rod spherules, as well as in
      photoreceptors, including associated interphotoreceptor matrices (IPM), attention
      has been directed only to those in the IPM. In this study, cloning of the O
      linked glycoproteins not only in the IPM but also in the region including the
      cone pedicles and rod spherules was attempted. METHODS: The cDNA for the core
      protein of the O-linked glycoprotein in the bovine retina was isolated by
      screening a bovine retinal cDNA library using a polyclonal antibody against the
      jacalin (a lectin specific for O-linked sugar residues)-binding glycoproteins
      (JBGPs) in the whole bovine retina. The expression of the JPGP core protein in
      the retina was examined by means of in situ hybridization histochemistry and
      immunohistochemistry. RESULTS: The cDNA was isolated and found to encode an
      entire core protein [predicted molecular mass (Mr): 101 kDa; rich in Ser and Thr;
      mucin-like] for the JBGPs with Mr of 120 and 135 kDa. The mRNA was expressed in
      both cone and rod photoreceptor cells. This protein was distributed in the cone
      pedicles and rod spherules as well as the photoreceptor layer. CONCLUSIONS:
      Mucinlike glycoproteins with Mr of 120 and 135 kDa may be synthesized in the cone
      and rod photoreceptor cells, respectively, and distributed not only in the
      photoreceptor layer (probably including the IPM) but also in the cone pedicles
      and rod spherules.

PMID- 10937596
TI  - Localization of cGMP-dependent protein kinase isoforms in mouse eye.
AB  - PURPOSE: To examine the expression of the major isoforms of cyclic guanosine
      monophosphate (cGMP)-dependent protein kinase (cGK) in mouse eye. METHODS:
      Immunohistochemical localization of cGMP in mouse eye cryosections was performed
      using an anti-cGMP antibody, followed by visualization with indirect fluorescence
      microscopy. The presence of types Ialpha, Ibeta, and II cGK mRNAs in mouse eye
      extracts was determined initially by RNase protection analysis. Further
      localization of cGK I and II mRNAs on cryosections was accomplished by in situ
      hybridization using digoxigenin-labeled cRNA probes and an alkaline phosphatase
      conjugated anti-digoxigenin antibody. Finally, cGK I protein was localized to
      subcellular areas within the retina using an anti-cGK I-specific primary
      antibody. RESULTS: In initial immunohistochemical experiments cGMP was present in
      numerous regions and layers within the eye and retina. Subsequent RNase
      protection studies demonstrated that cGK Ialpha, Ibeta, and II mRNAs were present
      in mouse eye and that type Ibeta mRNA were 6.6 and 30 times more abundant than
      type Ialpha and type II, respectively. By in situ hybridization, cGK I mRNA was
      localized to photoreceptor inner segments and the ganglion cell and inner nuclear
      layers of the retina, and lesser amounts were found in the ciliary epithelium,
      lens, and cornea. The cGK II mRNA expression pattern was similar but not
      identical with that of cGK I. Finally, within the retina, cGK I protein was most
      abundant in the inner plexiform layer, with significant amounts in ganglion cells
      and photoreceptor inner segments as well. CONCLUSIONS: The presence of these cGK
      isoforms in discrete areas throughout the eye suggests multiple roles for the
      cGMP-dependent signal transduction system in the regulation of physiologic and
      pathologic ocular processes.

PMID- 10937597
TI  - Pentoxifylline inhibition of vasculogenesis in the neonatal rat retina.
AB  - PURPOSE: The zeta isozyme of protein kinase C (PKC) is essential for activation
      of the transcription factor nuclear factor (NF)kappaB and transcription of
      vascular endothelial growth factor (VEGF). This study examined the antiangiogenic
      potential of an existing drug, pentoxifylline (PTX), which inhibits PKC-dependent
      activation of NFkappaB and is reported to prevent hypoxia-induced expression of
      VEGF. METHODS: Neovascularization was induced by maintaining neonatal rats for 10
      full days in 80% oxygen, interrupted daily by 30 minutes in room air followed by
      a progressive return to 80% oxygen. On experimental day 11, they were placed in
      room air until they were killed on day 17. Daily intraperitoneal injections of
      PTX in saline (25 or 75 mg/kg per day), or saline alone, were administered from
      day 6 through day 16. Retinal neovascularization was scored, and avascular areas
      (AVAs) were measured in ADPase stained retinas. RESULTS: PTX inhibited radial
      extension of retinal vessels, causing increases in AVA of 65% (P < 0.01) and 33%
      (P < 0.15) at the lower and upper doses, respectively. A significant increase in
      mean neovascular score was seen at the lower dose (P < 0.0001), but analysis of
      variance indicated that neovascularization was strongly and positively influenced
      by the AVA (P < 0.0001) and only weakly stimulated by PTX (P < 0.05).
      CONCLUSIONS: Systemic PTX significantly inhibited VEGF-mediated retinal
      vasculogenesis, but was not effective in reducing neovascularization in the
      oxygen-exposed neonatal rat.

PMID- 10937598
TI  - Rapid glutamatergic alterations in the neural retina induced by retinal
      detachment.
AB  - PURPOSE: Retinal detachment induces neurochemical changes in the neural retina
      over a span of days to weeks. However, little information is available on the
      acute response in the retina to detachment. METHODS: Distribution of the
      neurotransmitters glutamate, glycine, and gamma-aminobutyric acid (GABA) and the
      metabolic amino acids aspartate and glutamine was examined immunocytochemically
      from 5 to 30 minutes and at 3 hours after retinal detachment in a salamander
      eyecup preparation. RESULTS: Glutamate showed a rapid depletion from neuronal
      cell bodies in detached retina, whereas Muller cells, which normally sequester
      and metabolize glutamate, showed increased immunolabeling for glutamine. Changes
      occurred exclusively in detached retinal regions of the eyecup. Aspartate, a
      precursor for glutamate synthesis, also showed decreased labeling in neuronal
      cell bodies in detached retinal regions, although these changes were not as
      striking as those observed for glutamate. In contrast, the distributions of the
      inhibitory amino acid neurotransmitters glycine and GABA were not affected
      appreciably by acute retinal detachment. CONCLUSIONS: These results indicate that
      retinal detachment induces rapid, localized alterations in the glutamatergic
      system of the neural retina that are consistent with a massive efflux of neuronal
      glutamate and concomitant alterations in glutamate metabolism. An acute efflux of
      neuronal glutamate in detached retina could contribute to excitotoxicity and to
      the initiation of structural alterations and changes in gene expression; it is
      also consistent with reported neurochemical changes associated with longer term
      retinal detachment.

PMID- 10937599
TI  - Age- and disease-related changes of calcium channel-mediated currents in human
      Muller glial cells.
AB  - PURPOSE: To determine whether the expression of voltage-gated Ca2+ channels in
      human Muller glial cells changes during normal aging and in cells from patients
      with proliferative vitreoretinopathy (PVR). METHODS: Muller cells were
      enzymatically isolated from retinas of healthy donors and from excised retinal
      pieces of patients with PVR, and the whole-cell, voltage-clamp technique was used
      to characterize the current densities of transient, low-voltage-activated calcium
      channels and of sustained. high-voltage-activated calcium channels, respectively.
      To obtain maximal currents through both channel types, Na+ ions were used as the
      charge carrier. RESULTS: During normal aging, Muller cells developed a
      hypertrophy, as indicated by an increase of the cell membrane capacitance. The
      mean membrane capacitance of cells from aged donors (> or = 60 years old) was
      elevated by 25% compared with cells from younger donors. The hypertrophy was not
      accompanied by a changed density of low-voltage-activated currents, whereas the
      density of the high-voltage-activated currents was enhanced by 76%. The density
      of the high-voltage-activated currents increased in correlation with the increase
      of the cell membrane capacitance and with the age of the donors. In the case of
      PVR, Muller cells displayed a strong hypertrophy accompanied by a downregulation
      of both current types by approximately 65%. CONCLUSIONS: Both normal aging and
      PVR cause a gliotic reactivity of human Muller cells, as indicated by their
      hypertrophy. The type of reactivity, however, differs between the two conditions.
      Normal aging is accompanied by an increased expression of voltage-gated Ca2+
      channels, whereas in PVR Ca2+ channel expression is decreased.

PMID- 10937600
TI  - The uniform field and pattern ERG in macaques with experimental glaucoma: removal
      of spiking activity.
AB  - PURPOSE: To determine whether the uniform field and pattern ERGs that are reduced
      in macaque eyes with experimental glaucoma have the same inner-retinal origins.
      METHODS: ERGs were recorded from 14 anesthetized adult macaques using DTL
      electrodes. Six monkeys had laser-induced experimental glaucoma, and two others
      received intravitreal injections of tetrodotoxin (TTX, 6 microM) to block spiking
      activity of inner-retinal neurons. The remaining 6 animals were normal. Uniform
      fields and grating patterns (0.1-3 cpd) were square-wave modulated at 1.7 Hz
      (transient) and 8 Hz (steady state). The test field (42 degrees x 32 degrees) had
      a mean luminance of 44 cd/m2 and a contrast of 10% to 82%. RESULTS: In normal
      eyes transient ERGs to uniform fields contained photopic negative responses
      (PhNR) after the b-wave and after the d-wave. Transient pattern
      electroretinograms (PERGs) at each contrast reversal showed positive (P50)
      potentials followed by negative (N95) potentials of time course similar to that
      of the PhNR. The PhNR and N95 were greatly reduced or eliminated by experimental
      glaucoma and by TTX. Summing responses to luminance increments and decrements of
      the uniform field could simulate the PERG to low spatial frequency stimuli.
      Further, the PERG responses to high spatial frequencies were similar to the
      simulation in shape but slightly delayed in time. Experimental glaucoma and TTX
      had similar effects on the N95 of the simulated PERG as to those on the actual
      PERG. However, P50 was more reduced by experimental glaucoma than by TTX,
      indicating a nonspiking contribution to P50. For the steady state condition, the
      uniform field ERG, the simulated PERG, and the actual PERG all were affected by
      experimental glaucoma and TTX, indicating that they contained contributions from
      the spiking activity of ganglion cells. CONCLUSIONS: The changes in the uniform
      field and PERG responses produced by experimental glaucoma are related and are
      largely a consequence of reduced spiking activity of ganglion cells and their
      axons. These findings raise the possibility that the uniform field ERG could
      serve as a useful alternative to the PERG in the assessment of clinical
      glaucomatous neuropathy.

PMID- 10937602
TI  - The 7 habits of highly effective psychopharmacologists, Part 4: developing and
      implementing the vision.

PMID- 10937601
TI  - The effect of contrast and size scaling on face perception in foveal and
      extrafoveal vision.
AB  - PURPOSE: To determine whether face perception can be equalized across the visual
      field by scaling size and contrast simultaneously. METHODS: Contrast
      sensitivities were measured for detection (N = 1) and identification (N = 2-8) of
      a target face as a function of size (0.4 degrees-10 degrees) across
      eccentricities (E = 0 degrees-10 degrees). RESULTS: In all conditions contrast
      sensitivity first increased and then saturated, as a function of stimulus size.
      Maximum sensitivity (Smax) decreased, whereas critical size (where S =
      Smax/square root(2)) increased with eccentricity and set size (N). At each set
      size, sensitivities from all eccentricities could be equated by double scaling-
      i.e., translation in horizontal (size) and vertical (contrast) dimensions on log
      log axes. Similarly, at each eccentricity, data from all set sizes could be
      superimposed using double scaling. Furthermore, all data could be superimposed
      onto the foveal detection curve when double scaled according to the equation F =
      1 + E/E2i + logN/logN2i + E(logN)/K, where i is horizontal or vertical. This
      equation incorporates the eccentricity (E2) and set size (N2), where contrast and
      size double, as well as the interaction term (K). CONCLUSIONS: Double scaling
      superimposes data. Not only is this possible across set sizes or eccentricities
      separately, but by combining their effects, a function is provided that collapses
      all data to a single curve, explaining all performance variation across
      eccentricity and set size. Our results support the proposition based on numeral
      recognition that failures of spatial scaling across eccentricities may simply
      reflect the need for scaling both size and contrast.

PMID- 10937603
TI  - Treatment of men with major depression: a comparison of sequential cohorts
      treated with either cognitive-behavioral therapy or newer generation
      antidepressants.
AB  - OBJECTIVE: This report compares response to cognitive-behavioral therapy (CBT)
      and pharmacotherapy in sequential cohorts of men with DSM-III-R major depression.
      METHOD: Patients were enrolled in consecutive standardized 16-week treatment
      protocols conducted in the same research clinic. The first group (N = 52) was
      treated with Beck's model of CBT, whereas the second group (N = 23) received
      randomized but open-label treatment with either fluoxetine (N = 10) or bupropion
      (N = 13). Crossover to the alternate medication was permitted after 8 weeks of
      treatment for antidepressant nonresponders. The patient groups were well matched
      prior to treatment. Outcomes included remission and nonresponse rates, as well as
      both independent clinical evaluations and self-reported measures of depressive
      symptoms. RESULTS: Despite limited statistical power to detect differences
      between treatments, depressed men treated with pharmacotherapy had significantly
      greater improvements on 4 of 6 continuous dependent measures and a significantly
      lower rate of nonresponse (i.e., 13% vs. 46%). The difference favoring
      pharmacotherapy was late-emerging and partially explained by crossing over
      nonresponders to the alternate medication. The advantage of pharmacotherapy over
      CBT also tended to be larger among the subgroup of patients with chronic
      depression. CONCLUSION: Results of prior research comparing pharmacotherapy and
      CBT may have been influenced by the composition of study groups, particularly the
      gender composition, the choice of antidepressant comparators, or an interaction
      of these factors. Prospective studies utilizing flexible dosing of modern
      antidepressants and, if necessary, sequential trials of dissimilar medications
      are needed to confirm these findings.

PMID- 10937604
TI  - Allergy to tartrazine in psychotropic drugs.
AB  - BACKGROUND: High psychiatric morbidity has been reported among those who complain
      of food intolerance or allergy. Many cases of food allergy or intolerance to
      drugs are not due to allergy to the food or drugs themselves, but to the
      additives used for coloring, flavoring, preserving, thickening, emulsifying, or
      stabilizing the product. Of various coloring dyes used, tartrazine (FD & C yellow
      no. 5) is the color most frequently incriminated in producing allergic reactions.
      The exact epidemiology and pattern of allergic reactions to tartrazine in
      psychotropic drugs have not been frequently studied and reported. METHOD: The
      present study included consecutive outpatients (May 1996 to April 1998) who
      developed allergic reactions or intolerance to tartrazine in psychotropic drugs.
      Total patients exposed to tartrazine-containing drugs were also recorded. The
      subjects showing allergic reactions to tartrazine were then exposed to non
      tartrazine-containing brands. RESULTS: Of 2210 patients exposed to tartrazine
      containing drugs, 83 (3.8%) developed allergic reactions. The symptoms subsided
      within 24 to 48 hours of stopping the drug. None of the patients showed allergy
      to non-tartrazine-containing brands. History of allergy to tartrazine was present
      in 13.2%, and 15.7% of patients had a history of aspirin sensitivity. CONCLUSION:
      Tartrazine allergy should be considered in patients developing drug allergy,
      because it would require changing the brand rather than stopping treatment with
      that drug.

PMID- 10937605
TI  - The Texas Medication Algorithm Project Patient and Family Education Program: a
      consumer-guided initiative.
AB  - Educating patients with mental illness and their families about the illness and
      its treatment is essential to successful medication (disease) management.
      Specifically, education provides patients and families with the background they
      need to participate in treatment planning and implementation as full "partners"
      with clinicians. Thus, education increases the probability that appropriate and
      accurate treatment decisions will be made and that a treatment regimen will be
      followed. The Texas Medication Algorithm Project (TMAP) has incorporated these
      concepts into its philosophy of care and accordingly created a Patient and Family
      Education Program (PFEP) to complement the utilization of medication algorithms
      for the treatment of schizophrenic, bipolar, and major depressive disorders. This
      article describes how a team of mental health consumers, advocates, and
      professionals developed and implemented the PFEP. In keeping with the TMAP
      philosophy of care, consumers were true partners in the program's development and
      implementation. They not only created several components of the program and
      incorporated the consumer perspective, but they also served as program trainers
      and advocates. Initially, PFEP provides basic and subsequently more in-depth
      information about the illness and its treatment, including such topics as symptom
      monitoring and management and self-advocacy with one's treatment team. It
      includes written, pictorial, videotaped, and other media used in a phased manner
      by clinicians and consumer educators, in either individual or group formats.

PMID- 10937607
TI  - Measuring patient symptom change on rural psychiatry units: utility of the
      symptom checklist-90 revised.
AB  - BACKGROUND: Mental health service providers have seen an increased need for
      demonstrating symptom reductions during the past decade. This change has been
      particularly evident to those working in inpatient psychiatry facilities where
      there is considerable need for a brief, easily administered, and low-cost means
      of tracking symptom change. The current study evaluated the utility of using the
      Symptom Checklist-90 Revised for tracking symptom reductions in patients admitted
      to rural adolescent and adult psychiatry units. METHOD: Consecutive admissions to
      adolescent (N = 104) and adult (N = 125) psychiatry units located in a rural
      community hospital served as subjects. The mean length of stay was 8 days for
      adolescents and 7 days for adults. Patients were administered the Symptom
      Checklist-90 Revised at admission and just prior to discharge. Psychiatrists
      provided a DSM-IV primary diagnosis for each patient. RESULTS: Principal
      component analyses on both the adolescent and adult admission and discharge
      Symptom Checklist-90 Revised subscales resulted in a 1-factor solution. Repeated
      measures ANOVAs demonstrated the Global Severity Index to be a sensitive measure
      of clinically significant admission-to-discharge symptom change. Analyses using
      psychiatrist-assigned diagnoses revealed that all diagnostic categories evinced
      significant admission-to-discharge symptom reductions. DISCUSSION: Implications
      for using the Symptom Checklist-90 Revised to evaluate clinically significant
      symptom changes on rural inpatient psychiatry units are discussed.

PMID- 10937606
TI  - Effects of donepezil on emotional/behavioral symptoms in Alzheimer's disease
      patients.
AB  - BACKGROUND: This open-label study examined the effects of the reversible
      cholinesterase inhibitor donepezil on emotional/behavioral symptoms in
      Alzheimer's disease (AD) patients. METHOD: Patients were diagnosed as having
      probable/possible AD by National Institute of Neurological and Communicative
      Disorders and Stroke/Alzheimer's Disease and Related Disorders Association
      (NINCDS/ADRDA) criteria. This study used the CERAD Behavior Rating Scale for
      Dementia (CBRSD) and its subscales to evaluate a group of 25 AD patients treated
      with donepezil. Dosage was increased at 4 months for most patients from 5 to 10
      mg q.h.s. Analysis of variance was used to compare scores over a period of 12
      months. These patients were also compared, using t tests, to a reference group
      that had received no donepezil or other anticholinesterase. RESULTS: Donepezil
      administration was associated with improvement in Mini-Mental State Examination
      (MMSE) and CBRSD total scores at 3-month evaluation (p< or =.05). CBRSD
      depression and behavioral dysregulation scores improved transiently at 4 months
      (p< or =.05). MMSE, CBRSD total, CBRSD depression, and CBRSD behavioral
      dysregulation scores returned to baseline levels at 12 months, in contrast to the
      reference group, whose MMSE and CBRSD total scores worsened minimally over the 12
      months. CONCLUSION: Donepezil has a mildly positive effect on
      emotional/behavioral symptoms in AD in addition to its effect on cognitive
      function.

PMID- 10937608
TI  - Comparative efficacy of risperidone and clozapine in the treatment of patients
      with refractory schizophrenia or schizoaffective disorder: a retrospective
      analysis.
AB  - BACKGROUND: Clozapine is effective in up to 60% of patients with refractory
      schizophrenia, whereas the efficacy of risperidone remains unknown. This
      retrospective study examined the relative efficacy of these drugs in chronically
      institutionalized patients refractory to conventional antipsychotic agents.
      METHOD: A total of 24 patients who at different time periods had received
      adequate trials of both clozapine and risperidone and met our inclusion criteria
      for minimum dose and duration of each trial were included; for clozapine, a
      minimum dose of 300 mg/day had to be maintained for at least 12 weeks, and for
      risperidone, a minimum dose of 6 mg/day for at least 6 weeks. Information
      obtained from systematic retrospective chart review was blindly rated by 2
      psychiatrists using the 7-point Clinical Global Impressions-Improvement (CGI-I)
      scale on overall clinical state and along specific symptom domains of positive
      symptoms, negative symptoms, and aggressive behavior. RESULTS: The mean +/- SD
      dose was 520+/-94 mg/day for clozapine and 7.5+/-2.2 mg/day for risperidone.
      Fourteen patients (58%) were classified as responders to clozapine, while 6 (25%)
      responded to risperidone (CGI-I score of 1 or 2); on specific symptom domains,
      response rates to clozapine were 38% (9/24) on positive symptoms, 29% (7/24) on
      negative symptoms, and 71% (12/17) on aggressive behavior. For risperidone,
      response rates were 17% (4/24) on positive symptoms, 8% (2/24) on negative
      symptoms, and 41% (7/17) on aggressive behavior. CONCLUSION: The results of this
      study support the utility of first giving a risperidone trial in a treatment
      algorithm for refractory patients because of its better risk/benefit profile
      compared with clozapine. Clozapine, however, remains our gold standard in the
      management of these patients.

PMID- 10937609
TI  - The relationship between types and severity of repetitive behaviors in Gilles de
      la Tourette's disorder and obsessive-compulsive disorder.
AB  - BACKGROUND: This study investigated which categories of obsessive-compulsive and
      Tourette-related behaviors in Gilles de la Tourette's disorder and obsessive
      compulsive disorder (OCD) without tics are experienced as most severe across the
      study groups and what the differences are in symptom distribution between the
      study groups. METHOD: Fourteen subjects with both Tourette's disorder and OCD, 18
      subjects with Tourette's only, 21 subjects with OCD (no tics), and 29 control
      subjects were studied using a semistructured interview designed to equally assess
      Tourette- and OCD-related behaviors according to DSM-III-R criteria. Each
      reported repetitive behavior was evaluated on the presence of anxiety and on goal
      directedness. Anxiety-related items were categorized as obsessions or compulsions
      and non-anxiety-related items as impulsions. Severity of each reported item was
      assessed with respect to time per day consumed and amount of distress and
      interference induced by the item. Following these criteria, each reported item
      was classified as a symptom, a subthreshold symptom, or just as being present.
      RESULTS: Across the study groups, obsessions were experienced as more severe than
      (Tourette-related) impulsions and compulsions. Within the study groups, patients
      with both Tourette's disorder and OCD reported more symptomatic Tourette-related
      impulsions, such as mental play, echophenomena, and impulsive or self-injurious
      behaviors; less overall symptomatic obsessions; and less symptomatic washing than
      patients with OCD (no tics). The differences among individuals with Tourette's
      with or without OCD reflected differences in symptom severity rather than
      differences in symptom distribution. CONCLUSION: Obsessions are more time
      consuming, distressing, and interfering than compulsions and impulsions.
      Furthermore, the symptomatic repetitive behaviors were distributed differently
      among patients with both Tourette's disorder and OCD and patients with OCD (no
      tics). Patients with Tourette's and OCD are phenomenologically more similar to
      Tourette's than to OCD. These differences possibly represent differences in
      underlying pathophysiology between Tourette's and tic-free OCD.

PMID- 10937610
TI  - Olanzapine augmentation for treatment-resistant obsessive-compulsive disorder.
AB  - BACKGROUND: Adding the atypical neuroleptic risperidone to a serotonin reuptake
      inhibitor (SRI) has benefited patients with treatment-refractory obsessive
      compulsive disorder (OCD). Since olanzapine and risperidone have similar
      serotonergic and dopaminergic receptor binding profiles, we tested the hypothesis
      that olanzapine augmentation would be beneficial in treatment-unresponsive OCD.
      METHOD: For this 8-week trial, we recruited 10 adult OCD patients (DSM-IV
      criteria) unresponsive to fluoxetine (> or =60 mg/day) for > or =10 weeks, which
      was continued throughout the trial. Other psychotropic medications were
      discontinued. Subjects had OCD for > or =1 year, a Yale-Brown Obsessive
      Compulsive Scale (Y-BOCS) score of > or =18, and no organic, psychotic, or other
      primary Axis I disorder. Two weeks after olanzapine, 2.5 mg/day, was added, and
      in the absence of responder status (Y-BOCS score decrease > or =25%) and limiting
      side effects, we increased the dose to 5 mg/day, and after 2 more weeks, to 10
      mg/day for 4 weeks. RESULTS: The subjects had failed a mean of 3.3 SRI trials
      (range, 1-5) and had a mean +/- SD baseline Y-BOCS score of 29.0 +/- 4.9. Nine
      patients completed the trial. The subjects' mean +/- SD endpoint Y-BOCS score was
      24.4 +/- 8.0 (a 16% decrease). The 3 responders' Y-BOCS scores dropped 68%, 30%,
      and 29%, but only 1 patient was rated "much improved." He maintained this
      improvement during a 6-month follow-up period taking olanzapine, 5 mg/day.
      Improvement in OCD was independent of improvement in mood symptoms. Six patients
      (60%) experienced significant weight gain. CONCLUSION: Olanzapine augmentation
      may benefit treatment-unresponsive OCD. Double-blind, placebo-controlled trials
      are warranted along with trials comparing risperidone and olanzapine
      augmentation.

PMID- 10937611
TI  - Predictors of relapse during fluoxetine continuation or maintenance treatment of
      major depression.
AB  - BACKGROUND: The goal was to examine predictors of relapse during
      continuation/maintenance treatment of major depression that had remitted
      following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data
      collected in a collaborative clinical trial including patients with DSM-III-R
      major depression at 5 university-affiliated outpatient psychiatry clinics. Three
      hundred ninety-five patients who remitted with fluoxetine therapy were randomly
      assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36
      weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for
      50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to
      identify predictors of time to relapse. RESULTS: In addition to the previously
      reported longitudinal pattern of response during acute treatment, neurovegetative
      symptom pattern was a predictor of fluoxetine benefit compared with placebo.
      Greater chronicity predicted poorer survival, which was not differential by
      treatment. The most robust advantage of fluoxetine was seen for patients with
      endogenous vegetative symptoms, chronic depression, and acute treatment response
      characterized by onset in the third week or later and persistence of response
      once attained. CONCLUSION: Both nonspecific pattern of response and
      neurovegetative symptoms characteristic of atypical depression were predictive of
      lack of fluoxetine efficacy in continuation/ maintenance treatment. These
      findings have importance for both clinical management and analyses of future
      maintenance trials.

PMID- 10937612
TI  - Lack of sertraline efficacy probably due to an interaction with carbamazepine.

PMID- 10937613
TI  - Increased lithium concentrations reported in patients treated with sulindac.

PMID- 10937614
TI  - Carbamazepine augmentation of clomipramine in the treatment of refractory
      obsessive-compulsive disorder.

PMID- 10937615
TI  - SSRI-TCA combination in the treatment of resistant depression.

PMID- 10937616
TI  - Use of electroconvulsive therapy in a state hospital: a 10-year review.
AB  - BACKGROUND: The use of electroconvulsive therapy (ECT) in the state hospital
      setting currently represents a very small percentage of the total overall use of
      this modality in the treatment of the mentally ill. METHOD: Using records kept by
      a state hospital, we retrospectively identified all patients who had received ECT
      between the years 1986 and 1995. A review of the records at the state hospital
      from where patients were referred and the university hospital where ECT was
      administered was undertaken. Demographic and clinical characteristics, reasons
      for referral, symptom profile, ECT parameters, clinical outcomes, and restraint/
      seclusion data were assessed. RESULTS: Over 10 years, 21 patients were treated
      with ECT, representing 0.4% of all admissions to the state hospital. Of these
      subjects, 17 records could be retrieved. The majority were women (N = 12; 71%)
      and were diagnosed with a mood disorder. Ten subjects (59%) were over the age of
      60 years, 4 of whom were 70 years or older. Most patients had a state hospital
      length of stay of 1 year or less. The mean number of ECT treatments was 12.2.
      There were no medical complications that led to premature termination of ECT.
      Eleven patients (65%) were discharged either directly from the university
      hospital or within 10 days of readmission to the state hospital. Six of 7
      patients who had restraint and seclusion episodes prior to ECT were found to have
      no further episodes afterwards. The seventh experienced a dramatic decrease in
      number and total hours of episodes. CONCLUSION: For a substantial minority of
      patients in this state hospital setting, ECT appears to have been an effective
      and safe form of treatment, and its use should be considered early rather than
      late in the course of hospitalization.

PMID- 10937617
TI  - Localization of dominantly inherited isolated triphalangeal thumb.

PMID- 10937618
TI  - Localization of dominantly inherited isolated triphalangeal thumb to chromosomal
      region 7q36.
AB  - Triphalangeal thumb is an autosomal dominantly inherited form of abnormal
      preaxial skeletal development. In most families, however, the triphalangeal thumb
      phenotype coexists with a spectrum of limb deformities, including polydactyly and
      syndactyly. We describe two Iowa kindreds with triphalangeal thumb. In one
      family, with nine affected members, triphalangeal thumb was the only
      manifestation of limb deformity. We performed linkage analysis on both pedigrees,
      demonstrating a maximum LOD score of 6.23 with marker D7S559 on chromosome 7q36.
      This corresponds to a previous study of a candidate region of 450 kb in which
      data from several families with preaxial polydactyly were employed. Further
      analysis of the unique family with isolated triphalangeal thumb in the current
      study may demonstrate allelic variability of the gene involved in these
      disorders.

PMID- 10937619
TI  - Chondrocyte-specific enhancer regions in the COMP gene.
AB  - The molecular events governing the differentiation of mesenchymal cells into
      chondrocytes and the expression of cartilage marker genes are poorly understood.
      Cartilage oligomeric matrix protein is a noncollagenous extracellular matrix
      protein with a relatively cartilage-specific spatial and temporal expression
      pattern. To understand the mechanisms controlling chondrocyte-specific expression
      of cartilage oligomeric matrix protein, we cloned 1.9 kb of the 5' flanking
      promoter sequence of the murine cartilage oligomeric matrix protein gene and
      identified two spatially distant cartilage-specific enhancer regions by deletion
      analysis. One element is situated proximally (proximal positive element: -125 to 
      75) and a second region is located distally (distal positive region: -1925 to 
      592) relative to the transcription start site. Interestingly, nucleotides within
      the proximal positive element are conserved between the mouse and human promoters
      and resemble consensus sites for the binding of members of the high mobility
      group class of transcription factors. Defining cartilage-specific regulatory
      elements in the cartilage oligomeric matrix protein promoter may provide useful
      molecular probes for identifying transcription factors that control acquisition
      of the chondrocytic phenotype.

PMID- 10937620
TI  - Regulation by IGF-I and TGF-beta1 of Swarm-rat chondrosarcoma chondrocytes.
AB  - The growth factors transforming growth factor-beta 1 and insulin-like growth
      factor-I influence a wide range of cellular actions, including the growth of
      several neoplastic cell types. Their role in the regulation of neoplastic
      chondrocytes remains unclear. We tested the hypotheses that transforming growth
      factor-beta 1 and insulin-like growth factor-I differentially regulate neoplastic
      chondrocytes and interact to modulate the mitotic and matrix synthetic activities
      of neoplastic chondrocytes. We used Swarm-rat chondrosarcoma chondrocytes to
      investigate the effect of each factor individually and of both factors in
      combination on [(3)H]thymidine incorporation into DNA and on [(35)S]sulfate
      incorporation into glycosaminoglycans. Each factor increased [(3)H]thymidine
      incorporation 2.7-fold: transforming growth factor-beta 1 achieved this effect at
      a 20-fold lower concentration than insulin-like growth factor-I. In contrast,
      insulin-like growth factor-I stimulated [(35)S]sulfate incorporation 3.5-fold;
      this was twice the maximal effect of transforming growth factor-beta 1.
      Transforming growth factor-beta 1 and insulin-like growth factor-I each decreased
      the proportion of newly synthesized glycosaminoglycans that were retained in the
      cells and pericellular matrix, indicating that the anabolic effect of these
      factors is only partly directed toward cell-associated matrix production. The
      mitogenic and matrix synthetic actions of insulin-like growth factor-I and
      transforming growth factor-beta 1 were synergistic. In concert, they increased
      [(3)H]thymidine incorporation approximately 12-fold, an effect three times
      greater than the sum of the maximal stimulation achieved by each factor
      individually. Similarly, transforming growth factor-beta 1 and insulin-like
      growth factor-I together increased glycosaminoglycan synthesis approximately two
      times more than the sum of their maximal individual effects. Taken together,
      these data indicate that these chondrosarcoma chondrocytes are positively
      regulated by insulin-like growth factor-I and transforming growth factor-beta 1
      and that these growth factors interact to augment the mitotic and matrix
      synthetic actions of the chondrocytes. If supported in human models, the
      sensitivity to growth factors of these cells suggests that interventions directed
      toward growth factor inhibition may be of therapeutic value.

PMID- 10937621
TI  - Inhibition of caspase-3-like activity prevents apoptosis while retaining
      functionality of human chondrocytes in vitro.
AB  - Apoptosis was induced in a human chondrocyte cell line, T/C 28a4, by treatment
      with various stimuli, including camptothecin, tumor necrosis factor-alpha,
      staurosporine, okadaic acid, and reduced serum conditions. All stimuli induced a
      cytosolic DEVDase activity, coincident with apoptosis. Caspase activities in the
      lysates were characterized and quantitated with peptide cleavage profiles. To
      confirm that the results were not related to the immortalized nature of the cell
      line, primary human chondrocytes also were shown to undergo apoptosis under
      similar conditions, which resulted in increased cytosolic DEVDase activity. There
      was little or no caspase-1 (interleukin-1beta-converting enzyme) or caspase-8
      like activity in the apoptotic cells. In all cases, the irreversible nonselective
      caspase inhibitor, Z-VAD-FMK, and the caspase-3-selective inhibitor, Ac-DMQD-CHO,
      inhibited DEVDase activity and apoptosis, whereas the caspase-1-selective
      inhibitor, Ac-YVAD-CHO, had no effect. Human chondrocytes were stably and
      transiently transfected with a type-II collagen gene (COL2A1) regulatory sequence
      driving a luciferase reporter as a specific marker of chondrocyte gene
      expression. Treatment of the cells with camptothecin or tumor necrosis factor
      alpha plus cycloheximide significantly inhibited COL2A1 transcriptional activity.
      Significantly, cotreatment with Z-VAD-FMK or Ac-DMQD-CHO maintained COL2A1
      reporter gene activity, indicating that the prevention of apoptosis by caspase-3
      inhibition was sufficient to maintain cell functionality as assessed by the
      retention of type-II collagen promoter activity.

PMID- 10937622
TI  - Cell attachment, collagen binding, and receptor analysis on bovine articular
      chondrocytes.
AB  - The purpose of this study was to investigate collagen receptors on primary bovine
      articular chondrocytes from full-thickness and different layers of bovine
      articular cartilage. Cytometric studies with antibodies showed that approximately
      56% of the chondrocytes from the superficial layer and 29% of the chondrocytes
      from the deep layer bound anti-annexin V. A similar tendency was found for alpha5
      and beta1 integrin antibodies. Flow cytometric analysis initially detected
      annexin V on chondrocytes following isolation; the level of detection
      subsequently decreased by 24 hours, whereas that of alpha5 and beta1 integrins
      increased. Treatment of chondrocytes with collagenase at 24 hours restored the
      initially high epitope recognition of annexin V, indicating masking of annexin V
      by newly formed collagen matrix. There was little effect on detection levels for
      beta1 integrin. Contrary to the specific matrix receptor expression, chondrocytes
      from superficial and deep layers differed little in attachment to immobilized
      types I and II collagens. However, the attachment was more effectively inhibited
      with anti-annexin V than with integrin antibodies. Competition studies with
      preparations of soluble collagens revealed a preferential binding of bovine type
      II collagen compared with bovine type-I collagen. Anti-annexin V antibodies
      inhibited binding of type-II collagen more effectively than anti-alpha5 or anti
      beta1 integrin antibodies. Evidently, under the in vitro conditions of this
      study, annexin V is the quantitatively predominant type-II collagen receptor on
      bovine articular chondrocytes. This opens a discussion of the possibly dualistic
      metabolic/mechanical annexin V-integrin receptor elements.

PMID- 10937623
TI  - Mechanical compression modulates proliferation of transplanted chondrocytes.
AB  - The presence of an appropriate number of reparative cells in an articular
      cartilage defect is probably necessary for consistent and successful repair.
      Following the transplantation of chondrocytes into a defect, cell proliferation
      may modulate local defect cellularity. Transplanted cells can be compressed
      during cartilage repair as a result of joint-loading or press-fitting a graft
      into a cartilage defect. The objective of this study was to characterize the
      proliferative response of chondrocytes after attachment to cartilage and
      application of static compressive stress between cartilaginous surfaces in an ex
      vivo model. The chondrocytes were isolated from adult bovine cartilage, cultured
      in high-density monolayer, resuspended, and then transplanted onto the surface of
      devitalized cartilage at a density of 250,000 cells/cm2. The total DNA content of
      transplanted cell layers increased steadily to a plateau by 5 days and
      represented a 4-fold increase in cell number during incubation in medium
      including serum and ascorbate. Over the culture period, the level of DNA
      synthesis ([3H]thymidine incorporation), on a per cell basis, decreased steadily
      (88% between days 0 and 6). The application of 24 hours of static compressive
      stress (0.06-0.4 MPa) to the adherent cells at 1 and 4 days after transplantation
      inhibited overall DNA synthesis by 70-approximately 87% compared with unloaded
      controls. After release from load, cell proliferation generally remained at low
      levels. The marked proliferation of chondrocytes when attached to cartilage
      without applied load and the inhibition of this proliferation by relatively low
      amplitude static compressive stress may be relevant to the occasional overgrowth
      of tissue in some chondrocyte transplantation procedures. The dosimetry of these
      effects suggests that the in vivo mechanical environment may have a marked effect
      on proliferation of transplanted chondrocytes.

PMID- 10937624
TI  - Simultaneous changes in the mechanical properties, quantitative collagen
      organization, and proteoglycan concentration of articular cartilage following
      canine meniscectomy.
AB  - The mechanical properties and microstructure of articular cartilage from the
      canine tibial plateau were studied 12 weeks after total medial meniscectomy. The
      organization of the birefringent collagen network was measured with quantitative
      polarized light microscopy to determine the thickness and the degree of
      organization of the superficial and deep zones. The zonal concentration of
      sulfated glycosaminoglycan was quantified with digital densitometry of safranin-O
      staining. Equilibrium compressive and shear properties, as well as dynamic shear
      properties, were measured at sites adjacent to those of microstructural analysis.
      The results evinced significant loss of cartilage function following
      meniscectomy, with decreases of 20-50% in the compressive and shear moduli. There
      was no evidence of alterations in the degree of collagen fibrillar organization,
      although a complete loss of the surface zone was seen in 60% of the samples that
      underwent meniscectomy. Meniscectomy resulted in a decreased concentration of
      sulfated glycosaminoglycan, and significant positive correlations were found
      between the equilibrium compressive modulus and the glycosaminoglycan content.
      Furthermore, the shear properties of cartilage correlated directly with collagen
      fibrillar organization measured at the superficial zone of corresponding sites.
      These findings demonstrate that meniscectomy leads to impaired mechanical
      function of articular cartilage, with significant evidence of quantitative
      correlations between cartilage microstructure and mechanics.

PMID- 10937625
TI  - Biomechanical investigations on chondromalacia of the knee after meniscal flap
      lesion and partial meniscal resection: an experimental model.
AB  - Meniscal tears and resections may cause chondral lesions of the knee. To
      eliminate muscular control during investigation of this problem, we designed a
      biomechanical setup based on a knee-joint simulator, ensuring physiological, free
      motion mobility of the joint. Fresh human knee specimens with intact cartilage
      were exposed to loads to 2,000 N at a frequency of 0.85 Hz during 48 hours of
      gait. After a preliminary test series, 18 specimens were divided into three
      groups: group I was tested with unchanged meniscal status, group II with
      arthroscopically induced mobile flap tears at the posterior horns of the menisci,
      and group III after partial resection of the posterior horns. Motion patterns
      between the groups changed after as little as a few hours due to increased
      translation in group III. Macroscopic and histological examination and scanning
      electron microscopy revealed severe chondromalacic changes after meniscal
      resection. We conclude that meniscal resection-however partial-may have
      considerable joint-damaging potential if muscle control is lacking whereas mobile
      flap tears maintain stability. Our findings might explain the differences in
      clinical reports on cartilage status after partial meniscal resection. This study
      underlines the importance of muscle training when active stabilisation of the
      knee is reduced after partial meniscal resection.

PMID- 10937626
TI  - Alterations in cartilage type-II procollagen and aggrecan contents in synovial
      fluid in equine osteochondrosis.
AB  - The etiology and pathophysiology of osteochondrosis remain poorly understood
      because it is difficult to obtain material from lesions in the early stage of
      this disease and because there is no satisfactory experimental animal model. We
      wished to determine whether there are changes in articular cartilage turnover in
      equine osteochondrosis, which closely resembles the human disease, by assaying
      cartilage matrix molecules in synovial fluids. We used immunoassays that measure
      a keratan sulfate epitope and the epitope 846 on the cartilage proteoglycan
      aggrecan and the C-propeptide of cartilage type-II procollagen, which is released
      following the synthesis of this molecule, to analyse synovial fluids from equine
      tarsocrural joints with and without osteochondrosis. In young horses with
      osteochondrosis, there was a significant increase of C-propeptide of type-II
      procollagen accompanied by a decrease in the 846 and keratan sulfate epitopes.
      The results identify differential alterations in aggrecan and type-II collagen
      turnover in the cartilage matrix in young animals with osteochondrosis that may
      contribute to the pathological degeneration of articular cartilage in this
      disease.

PMID- 10937627
TI  - Mechanical modulation of tenascin-C and collagen-XII expression during avian
      synovial joint formation.
AB  - The objective of this study was to investigate how temporal and spatial patterns
      of characteristic extracellular matrix molecules are altered in the absence of
      normal functional skeletal muscle contractions during avian synovial joint
      development. By using in situ detection of protein and mRNA expression in
      developing avian feet and femorotibial joints from a wide range of developmental
      stages, we demonstrate that the morphological abnormalities that result from
      embryonic immobilization are associated with altered patterns of tenascin-C and
      collagen-XII expression within developing joint structures. As the joints fuse in
      immobilized embryos, the cells of the presumptive articular surface differentiate
      from flattened fibroblasts to more rounded chondrocytes and collagens XII and I
      are no longer detected at sites of complete joint fusion. Although the expression
      of collagen XII persists at normal levels elsewhere within the immobilized joint,
      tenascin-C expression is diminished within the chondroepiphysis, synovium, and
      tendons, as well as within the remains of the fibrous articular surface. This
      effect is most notable for the shortest tenascin variant (Tn190) within the
      chondroepiphysis and the largest variant (Tn230) within tendons, synovium, and
      the fibrous surface layer of the joint. This study thus provides in vivo support
      of previous in vitro work that suggests that tenascin expression is sensitive to
      external changes in mechanical loading environment. However, these data do not
      support a similar conclusion for collagen XII during early development.

PMID- 10937628
TI  - Amelioration of disease severity by intraarticular hylan therapy in bilateral
      canine osteoarthritis.
AB  - Because of its high molecular weight, the glycosaminoglycan molecule hyaluronan
      is responsible for the viscoelastic properties of normal synovial fluid. In
      osteoarthritis, the concentration and molecular weight of hyaluronan in synovial
      fluid is diminished: this impairs the ability of synovial fluid to effectively
      lubricate joints, absorb loads, and exert anti-inflammatory effects. Using a
      bilateral anterior cruciate-ligament transection and partial neurectomy canine
      model of osteoarthritis, this study examined the effect of viscosupplementation
      with hylan G-F 20 as a treatment for osteoarthritis. Twelve dogs underwent
      bilateral arthroscopic anterior cruciate-ligament transections and partial
      neurectomy of the knee joints. Beginning 1 week after the operation, six dogs
      received three weekly 500-microl injections of hylan G-F 20 in one knee and a
      sham injection of saline solution in the contralateral knee (early-treatment
      group). The remaining six animals underwent the same treatment 2 months following
      the procedure (late-treatment group). All dogs were killed at 8 months, and both
      knees were evaluated for gross pathology, histology, and proteoglycan content. In
      addition, with use of 500-MHz [1H] magnetic resonance spectroscopy, the synovial
      fluid from both knees was assessed for changes in metabolic profile. Differences
      in outcome were analyzed with paired t tests. Gross pathological and histological
      examination revealed significantly less severe changes of osteoarthritis in knees
      treated with hylan G-F 20 2 months after surgery than in the contralateral
      untreated knees. Magnetic resonance spectroscopy of the specimens in this late
      treatment group showed significantly decreased glucose concentrations and
      significantly elevated isoleucine levels in the synovial fluid from knees treated
      with hylan G-F 20 compared with the controls. Previous magnetic resonance
      spectroscopy had shown that glucose concentrations increase with the onset of
      osteoarthritis and eventually diminish in end-stage osteoarthritis. The three
      injections of hylan were given after osteoarthritis was established, and the
      severity of the disease was ameliorated in the treated knees 6 months after
      treatment. This occurred although hylan G-F 20 is almost certainly cleared from
      joints by lymphatics within 4 weeks of injection, suggesting that hylan therapy
      can retard the progression of osteoarthritis for periods of time extending beyond
      the intraarticular residence time of the injected molecules and that hylan
      injections given at relatively early stages of osteoarthritis may have a
      chondroprotective effect. No changes in outcome were noted in the animals that
      received hylan G-F 20 immediately following surgery.

PMID- 10937629
TI  - Effect of freeze-drying and gamma irradiation on the mechanical properties of
      human cancellous bone.
AB  - Freeze-drying and gamma irradiation are commonly used for preservation and
      sterilization in bone banking. The cumulative effects of preparation and
      sterilization of cancellous graft material have not been adequately studied,
      despite the clinical importance of graft material in orthopaedic surgery. Taking
      benefit from the symmetry of the left and right femoral heads, the influence of
      lipid extraction followed by freeze-drying of a femoral head and a final 25-kGy
      gamma irradiation was determined, with the nonirradiated, nonprocessed
      counterpart as the control. Five hundred and fifty-six compression tests were
      performed (137 pairs for the first treatment and 141 pairs for the second).
      Mechanical tests were performed after 30 minutes of rehydration in saline
      solution. Freeze-dried femoral heads that had undergone lipid extraction
      experienced reductions of 18.9 and 20.2% in ultimate strength and stiffness,
      respectively. Unexpectedly, the work to failure did not decrease after this
      treatment. The addition of gamma irradiation resulted in a mean drop of 42.5% in
      ultimate strength. Stiffness of the processed bone was not modified by the final
      irradiation, with an insignificant drop of 24%, whereas work to failure was
      reduced by a mean of 71.8%. Freeze-dried bone was a bit less strong and stiff
      than its frozen control. Its work to failure was not reduced, due to more
      deformation in the nonlinear domain, and it was not brittle after 30 minutes of
      rehydration. Final irradiation of the freeze-dried bone weakened its mechanical
      resistance, namely by the loss of its capacity to absorb the energy (in a plastic
      way) and a subsequent greater brittleness.

PMID- 10937630
TI  - Age, gender, and bone lamellae elastic moduli.
AB  - To enhance preventative and therapeutic strategies for metabolic bone diseases
      and bone fragility disorders, we began to explore the physical properties of bone
      tissue at the cellular level. Proximal femurs were harvested from 27 cadavera (16
      male and 11 female) for in vitro measurement of the mechanical properties. We
      measured the variations in lamellar-level elastic modulus and hardness in human
      bone as a function of age and gender to identify microstructural properties
      responsible for age and gender-related reductions in the mechanical integrity.
      The lateral femoral necks were examined, and age, gender, height, body mass, and
      body mass index were not found to correlate with lamellar-level elastic modulus
      or hardness. This result was consistent for osteonal, interstitial, and
      trabecular tissue. These data suggest that increased bone mass maintenance, known
      to occur in heavier individuals, is not accompanied by increases in the lamellar
      level elastic modulus or hardness. The independence of elastic modulus and
      hardness from age and gender suggests that age and gender-related decreases in
      mechanical integrity do not involve alterations in elastic modulus or hardness of
      the extracellular matrix. Lamellar-level ultimate, fatigue, and fracture
      toughness properties should also be investigated. Other factors, such as tissue
      mass and organization, may also contribute to age and gender-related decreases in
      the mechanical integrity.

PMID- 10937631
TI  - Metabolic activity of a new atrophic nonunion model in rabbits.
AB  - The aetiology of atrophic nonunions is not well understood: they are often
      thought to be nonreactive and metabolically inactive. Investigation of their
      biological processes is hampered by the lack of a useful animal model. Current
      models involve either wide segmental excision of the diaphysis or interposition
      of Silastic to impede the normal healing processes. neither of which resembles
      the clinical situation. We therefore aimed to establish a model of atrophic
      nonunion that more closely resembles the clinical situation and to use this model
      to evaluate the metabolic activity of the gap tissue of the nonunion. A simple
      and reliable model of atrophic nonunion has been developed in rabbits. It more
      closely represents the clinical situation by avoiding large segmental excisions
      and the interposition of foreign materials. Clinical, radiological, and
      histological data support the diagnosis of atrophic nonunion in the model. The
      concentration of adenosine triphosphate in the gap tissue of the nonunion served
      as a marker of metabolic activity. The gap tissue of established atrophic
      nonunions had a significantly higher concentration of adenosine triphosphate than
      did the control specimens. In this model, the gap tissue is metabolically active;
      therefore, under certain conditions, it may be possible to induce union if the
      correct stimulus is provided.

PMID- 10937632
TI  - Femoral structure and stiffness in patients with femoral neck fracture.
AB  - Bone morphological characteristics may relate to the risk of hip fracture. We
      applied finite element modeling to radiologic data for two groups of women in
      vivo to address two questions: (a) Do individuals who have just sustained a
      femoral neck fracture exhibit reduced three-dimensional structural stiffness? and
      (b) Are victims of hip fracture disproportionately more susceptible to loads
      sustained in a fall than to stance-type loads? Ten white women (age: 64-76 years)
      who had just sustained a femoral neck fracture and 18 female volunteers (age: 65
      76 years), matched as groups for race, age. and body mass index, were evaluated.
      From quantitative computed tomography scans, femoral morphometric and volumetric
      cancellous density measurements were obtained and a finite element model was
      constructed. Two load conditions were simulated: single-stance phase and lateral
      fall. Global stiffness values were determined for each model. The cancellous bone
      density was significantly lower at the femoral neck and the femoral neck and head
      diameters were significantly larger in the women in the fracture group than in
      those in the control group. The stiffness of the proximal femur did not differ
      significantly between the groups for either load condition. An apparently linear
      relationship was found for stiffness at stance load compared with stiffness at
      fall load (r = 0.84, p < 0.001). and slopes did not differ significantly between
      the groups. Although cancellous density was reduced at the fracture site in
      patients with femoral neck fractures. this did not result in a reduction in the
      predicted bone stiffness. Previous studies have established a very strong
      relationship between the stiffness and strength of bone. Since these modeling
      methods were thoroughly validated ex vivo, we conclude that although decreased
      bone density at the femoral neck may predict where fracture initiates, the risk
      of hip fracture per se may be more strongly dependent on issues such as the risk
      of falling and fall biomechanics than on the structural characteristics of bone.

PMID- 10937633
TI  - Multidrug resistance-1 gene expression does not increase during tumor progression
      in the MGH-OGS murine osteosarcoma tumor model.
AB  - In addition to its possible role in drug resistance, expression of the multidrug
      resistance-1 gene may also be associated with a more malignant phenotype and
      tumor progression. This study evaluated its expression during tumor progression
      in the MGH-OGS transplantable murine osteosarcoma tumor model. Three variables of
      tumor progression were analyzed: tumor size, local recurrence, and metastasis.
      With a highly sensitive reverse transcription-polymerase chain reaction method,
      mRNA levels of multidrug resistance-1 were compared in primary tumors of
      different sizes. In addition, the levels were compared in primary, locally
      recurrent, and metastatic tumors isolated from individual mice. No significant
      difference was found in the levels of expression with increasing primary tumor
      size. In addition, the levels in primary, locally recurrent, and metastatic
      tumors were not significantly different. Our results indicate that--at least in
      the MGH-OGS tumor model, which is analogous to the majority of spontaneously
      occurring human osteosarcomas in that it has low levels of multidrug resistance
      1/P-glycoprotein and is sensitive to doxorubicin--there is no evidence of
      upregulation of multidrug resistance-1 expression during tumor progression.

PMID- 10937634
TI  - Mechanical behavior of two hamstring graft constructs for reconstruction of the
      anterior cruciate ligament.
AB  - We compared the mechanical behavior of two common hamstring graft constructs that
      are frequently used for reconstruction of the anterior cruciate ligament-Graft A:
      quadrupled semitendinosus tendon fixed with titanium button/polyester tape and
      suture/screw post, and Graft B: a double semitendinosus and double gracilis
      tendon fixed with a cross pin and two screws over washers. The experimental
      protocol used to evaluate each graft construct included stress relaxation (with
      and without preconditioning), cyclic loading, and a tensile load-to-failure test.
      The amount of stress relaxation without preconditioning was 60.6% for Graft A and
      53.8% for Graft B. With preconditioning, it significantly decreased (p < 0.05) to
      48.7 and 42.3%, respectively. Elongation of the graft construct in response to
      100 cycles of loading (20-150 N) was 1.8 and 0.6% of the original length for
      Grafts A and B, respectively. However, after a series of five cyclic loading
      tests, the residual permanent elongation for each construct was 3.8 +/- 1.2 and
      0.3 +/- 0.2 mm, a significant difference (p < 0.05) between the two graft
      constructs. Further analysis found more than 90% of the permanent elongation in
      the proximal and distal regions of Graft A, which consisted of polyester tape
      tied to a titanium button (proximal) and sutures tied around a screw post
      (distal). The tensile load-to-failure tests also revealed significant differences
      (p < 0.05) between the two graft constructs. Linear stiffness was 32 +/- 1 and
      119 +/- 19 Nmm and ultimate load was 415 +/- 36 and 658 +/- 128 N for Grafts A
      and B, respectively. For Graft A, the polyester tape consistently failed; for
      Graft B, slippage or tearing from the washers was the mode of failure. We
      conclude that a quadruple-hamstring graft fixed over a cross pin proximally and
      with metal washers distally (Graft B) has less permanent elongation in response
      to cyclic loading and has structural properties superior to those of a graft
      construct that includes suture and tape material (Graft A). The large permanent
      elongation following repetitive loading of a graft construct with tape and suture
      material during the early postoperative period is of concern.

PMID- 10937635
TI  - Pregnancy affects cellular activity, but not tissue mechanical properties, in the
      healing rabbit medial collateral ligament.
AB  - Recently, evidence has been accumulating that ligament and joint laxity is
      altered in women and rabbits during pregnancy. Furthermore, many female
      adolescents injure ligaments through participation in athletics and other
      activities. Therefore, to determine whether pregnancy has different effects on
      the injured and uninjured medial collateral ligament of the rabbit knee, we
      investigated cellular changes (mRNA levels) and alterations in tissue properties
      (biomechanics) accompanying pregnancy in animals with the medial collateral
      ligament injured during adolescence and bred for their primigravid pregnancy as
      young adults. Assessment of mRNA levels for matrix molecules, matrix
      metalloproteinases and tissue inhibitor of metalloproteinase-1, growth factors
      and sex hormone receptors, inflammatory cytokines, inducible nitric oxide
      synthase, and cyclooxygenase-2 by semiquantitative reverse transcription
      polymerase chain reaction revealed that pregnancy had different impacts on scar
      and uninjured tissue for six of 15 genes assessed. A pregnancy-associated
      increase in laxity of the medial collateral ligament was observed for rabbits in
      the uninjured primigravida group; however, no increase was observed for injured
      rabbits during pregnancy. The injured ligament was already significantly more lax
      than the normal counterpart, and pregnancy did not lead to additional laxity or
      prevent the normal decline in laxity as the scar matured in nonpregnant animals.
      These results indicate that the impact of pregnancy on laxity and cell activity
      of the medial collateral ligament is dependent on whether the ligament is
      uninjured or injured. Pregnancy had no significant effect on structural
      (stiffness and failure load), material (stress at failure and Young's modulus),
      or viscoelastic (cyclic and static relaxation) properties of tissue from
      uninjured or injured medial collateral ligament. Therefore, the properties of the
      healing ligament were not adversely affected during pregnancy in this
      experimental model. However, it remains to be determined if these results with an
      injured medial collateral ligament can be extrapolated to the injured anterior
      cruciate ligament.

PMID- 10937636
TI  - Tumor necrosis factor-alpha/nuclear transcription factor-kappaB signaling in
      periprosthetic osteolysis.
AB  - Due to irreversible joint destruction caused by the various arthritides, more
      than 400,000 total joint arthroplasties are performed each year in the United
      States. As many as 20% of these require revision surgery because of aseptic
      loosening. The current paradigm to explain aseptic loosening is that wear debris
      generated from the prosthesis stimulates the release of proinflammatory cytokines
      (i.e., tumor necrosis factor-alpha and interleukins 1 and 6) following
      phagocytosis by resident macrophages. These cytokines, in turn, initiate an
      inflammatory response, with the development of an erosive pannus that stimulates
      bone resorption by osteoclasts. In support of this model, we have previously
      shown that human monocytes produce large quantities of tumor necrosis factor
      alpha in response to titanium particles in vitro. In the current study, we
      characterized the role of tumor necrosis factor-alpha/nuclear transcription
      factor-kappaB signaling in the proinflammatory response to titanium particles in
      vitro and in vivo. Using the mouse macrophage cell line J774, we showed that
      these cells produce an amount of tumor necrosis factor-alpha in response to
      titanium particles similar to that produced by human peripheral blood monocytes.
      The production of tumor necrosis factor-alpha was preceded by a drop in cellular
      levels of inhibitory factor-kappaBalpha protein and translocation of p50/p65
      nuclear transcription factor-KB to the nucleus 30 minutes after stimulation.
      Levels of tumor necrosis factor-alpha and inhibitory factor-kappaBalpha mRNA
      increased 30 minutes after stimulation, consistent with the activation of nuclear
      transcription factor-kappaB. Interleukin-6 mRNA was first seen 4 hours after the
      addition of the titanium particles, indicating that the production of this
      cytokine is secondary to the immediate nuclear transcription factor-kappaB
      response. To test the relevance of tumor necrosis factor-alpha/nuclear
      transcription factor-kappaB signaling in response to titanium particles in vivo,
      we adopted an animal model in which the particles were surgically implanted on
      the calvaria of mice. The animals displayed a dramatic histological response to
      the debris, with the formation of fibrous tissue and extensive bone resorption
      after only 1 week. With use of immunohistochemistry and tartrate-resistant acid
      phosphatase staining, tumor necrosis factor-alpha and osteoclasts were readily
      detected at the site of inflammation and bone resorption in the calvaria of the
      treated mice. By testing mice that genetically over-produce tumor necrosis factor
      alpha (hTNFalpha-Tg), those defective in tumor necrosis factor-alpha signaling
      (TNF-RI-/-), and those that are nuclear transcription factor-kappaB1-deficient
      (NFkappaB1-/-), we evaluated the importance of tumor necrosis factor
      alpha/nuclear transcription factor-kappaB signaling in the biological processes
      responsible for aseptic loosening. The hTNFalpha-Tg mice had a grossly
      exaggerated response, the TNF-RI(-/-) mice showed little evidence of inflammation
      or bone resorption, and the nuclear transcription factor-kappaB1(-/-) mice had an
      inflammatory response without bone resorption. On the basis of these results, we
      propose a model for periprosthetic osteolysis in which wear debris particles are
      phagocytosed by macrophages, resulting in the activation of nuclear transcription
      factor-kappaB and the production of tumor necrosis factor-alpha. Tumor necrosis
      factor-alpha directly induces fibroblast proliferation and tissue fibrosis and
      recruits or activates, or both, osteoclasts to resorb adjacent bone.

PMID- 10937637
TI  - Pressure-induced periprosthetic osteolysis: a rat model.
AB  - Recent animal experiments have indicated that oscillating fluid pressure at the
      interface of bone and implant can lead to osteolysis. However, external
      nonphysiologic saline solutions were used to generate the pressure in these
      studies. In the present study on 15 Sprague-Dawley rats, hydrostatic pressure
      fluctuations were applied to bone through body fluids, by compressing a soft
      tissue membrane adjacent to the proximal tibia. A titanium plate was fixed to the
      bone surface. After 28 days of osseointegration of the plate, a 1-mm-wide gap was
      created between it and the cortical bone and 5 days were given for fibrous tissue
      to form. Load was transmitted to this soft tissue by applying force on a piston
      mounted in the plate. In six rats, a cyclic pressure of 0.6 MPa was then applied
      to this tissue by 20 cycles twice a day with a frequency of 0.17 Hz for 5 days.
      The remaining rats served as controls, with the piston left untouched in its
      upper position. All of the rats were killed 10 days after creation of the gap.
      Histological sections were produced at a right angle to the loaded surface. In
      the pressurized specimens, osteoclastic bone resorption was dramatic. In all
      specimens, the original cortex was almost entirely resorbed but new woven bone
      had formed deeper in the marrow and walled off a cystic lesion. When necrotic
      remnants of the cortex were still in place, new woven bone was seen on the side
      away from the piston. This "lee effect" may indicate that bone formation was
      inhibited by fluid flow away from the pressurized tissue. The specimens with a
      nonloaded piston showed no signs of resorption. This new experimental model shows
      again that a moderate rise of hydrostatic pressure at the interface of bone and
      implant leads to considerable bone resorption. This could be a mechanism of
      prosthetic loosening.

PMID- 10937638
TI  - Effects of hydrosyapatite coating on Ti-6A1-4V implant-site infection in a rabbit
      tibial model.
AB  - To investigate the effect of implant type after direct contamination, a
      hydroxyapatite-coated or noncoated Ti-6A1-4V implant was inserted into both
      tibiae of 32 New Zealand White rabbits. Prior to implantation, the left tibia was
      contaminated with increasing concentrations of Staphylococcus aureus (10(2)-10(5)
      colony-forming units), ranging from very low (10(2)) to relatively high (10(5)).
      Four weeks after implantation, half of the tibial bone adjacent to the implant
      was harvested for bacteriological examination. Bacterial counts were quantified
      by plating serial dilutions. For the histological evaluation, sections of the
      implant with the remaining tibia were examined by semiquantitative scoring of
      infection parameters. The bacteriological data showed the inoculum dose and
      implant type to have a significant effect on the culture outcome: more bacteria
      were retrieved from the hydroxyapatite-coated implants than from the noncoated
      titanium implants. Histological evaluation showed an increased score for the
      infected left tibiae compared with their contralateral control. In addition, with
      increasing inoculum dosage, the difference between the two types of implant
      increased. We demonstrated that infections can occur with biocompatible,
      noncemented implants and that they are related to the dose of the original
      inoculum. Bacteria were more likely to grow onto or next to the hydroxyapatite
      implants than on titanium implants and resulted in a more severe
      histopathological characterization of infection.

PMID- 10937639
TI  - Biological and mechanical characteristics of the interface between a new swelling
      anchor and bone.
AB  - We recently evaluated the peak pullout loads for anchors made from our new
      copolymeric swelling-type material compared with anchors made of a nonswelling
      material. In vitro and in vivo peak pullout loads of these anchors were evaluated
      after different intervals of implantation in the lateral femoral condyles of New
      Zealand White rabbits. Scanning electron microscopy and energy dispersive x-ray
      analyses were additionally performed on selected retrieved samples after pullout
      to examine the characteristics of bone attachment to the implant. The mean peak
      pullout load was greater for the swelling anchors than for the nonswelling
      anchors after 48 hours in vitro (46.0 +/- 15.8 compared with 10.8 +/- 9.1 N, p =
      0.0541). After 2 weeks in vivo, it was significantly greater for the swelling
      anchors than for the nonswelling controls (177.7 +/- 41.3 compared with 53.7 +/-
      17.5 N, p = 0.0024). The peak pullout load was also greater for the swelling
      anchors after 8 weeks in vivo; however, this difference was less pronounced than
      at 2 weeks (101.8 +/- 35.0 compared with 58.9 +/- 9.7 N, p = 0.0508).
      Furthermore, the swelling implants tended to induce bone deposition at the bone
      implant interface. Results from this investigation reveal that the new family of
      dynamic implants has potential for applications requiring fixation to cancellous
      or osteoporotic bone.

PMID- 10937640
TI  - Anatomical effects of periosteal elevation.
AB  - Research that involves harvesting the periosteum is common. The exact technique
      of harvesting is rarely described; however, it may be of vital importance because
      techniques may vary in their ability to raise the osteogenic cambial layer, which
      is reported to be tightly adherent to the underlying cortex. This study was
      performed to define how the cambial and fibrous layers of the periosteum are
      affected by different techniques of stripping. The periosteum was raised from the
      tibia and the humerus of adult rabbits with four stripping techniques. The
      stripped bone surface was examined histologically and with a scanning electron
      microscope to determine whether the fibrous and cambial layers of the periosteum
      had been removed and whether there had been damage to the underlying cortex. The
      results from the two anatomical sites were the same. Raising the periosteum with
      cortical bone chips (shingling) or with a periosteal elevator removed both layers
      of the periosteum and caused considerable damage to the surface of the cortex.
      Raising the periosteum with a sharp scalpel or by simply pulling it off removed
      the fibrous layer but left the osteogenic layer intact adherent to the cortex. We
      conclude that some techniques of periosteal elevation fail to harvest the
      osteogenic layer and therefore may lead to unexpected experimental results. We
      suggest that authors describe the exact technique of periosteal stripping that
      was employed.

PMID- 10937642
TI  - Cartilage repair with autogenic perichondrium cell/polylactic acid grafts: a two
      year study in rabbits.
AB  - The repair of articular cartilage injuries remains a challenge. In this 2-year
      study, osteochondral defects in the femoral condyles of five rabbits were
      repaired with an autogenic perichondrium cell/polylactic acid graft and compared
      with a contralateral control in which the defect remained empty. The rabbits in
      the group with the grafts had a higher percentage of biologically acceptable
      repairs (100%) than did those in the control group (80%). According to the
      histologic and histomorphometric analyses, the grafts augmented the intrinsic
      healing. Nonetheless, the results for the grafts were tarnished by a depressed
      repair surface and a histologic appearance not equivalent to that of normal
      cartilage. The application of growth factors to this model may yield a clinical
      treatment.

PMID- 10937641
TI  - Rapid quantitative bioassay of osteoinduction.
AB  - We developed a reproducible, relatively rapid bioassay that quantitatively
      correlates with the osteoinductive capacity of demineralized bone matrix obtained
      from human long bones. We have found that Saos human osteosarcoma cells
      proliferate in response to incubation with demineralized bone matrix and that an
      index of this proliferative activity correlates with demineralized bone matrix
      induced osteogenesis in vivo. The bioassay (Saos cell proliferation) had an
      interassay coefficient of variation of 23 +/- 2% and an intra-assay coefficient
      of 11 +/- 1%. Cell proliferation was normalized to a standard sample of
      demineralized bone matrix with a clinically high osteoinductive capacity, which
      was assigned a value of one. The Saos cell proliferation for each sample was
      related to the standard and assigned a value placing it into the low (0.00-0.39),
      intermediate (0.40-0.69), or high (0.70-1.49) osteoinductive index group.
      Osteoinduction of human demineralized bone matrix was quantitated by expressing
      new bone formation as a function of the total bone volume (new bone plus the
      demineralized bone powder). The demineralized bone matrix was placed in pouches
      formed in the rectus abdominis muscles of athymic rats, and endochondral bone
      formation was assessed at 35 days following implantation, when marrow spaces in
      the ossicles were formed by new bone bridging the spaces between demineralized
      bone matrix particles. The proliferative index correlated with the area of new
      bone formation in histological sections of the newly formed ossicles. When the
      proliferative index (the osteoinductive index) was divided into low,
      intermediate, and high groups, the correlation between it and new bone formation
      (osteoinduction) was 0.850 (p < 0.0005) in 25 samples of demineralized bone
      matrix. There was no overlap in the osteoinduction stimulated between the samples
      with low and high osteoinductive indices. We conclude that the proliferation
      assay is useful for the routine screening of bone allograft donors for
      osteoinductive potential. Furthermore, the two-dimensional area of new bone
      formation, as it relates to total new bone area, is a quantitative measure of
      osteoinduction.

PMID- 10937643
TI  - Mediocrity is no standard: searching for self-respect in Clinical
      Neuropsychology.
AB  - While medicine moved from a training based in proprietary schools to university
      based education and board specialty examinations during the early part of this
      century, psychology has seemed to move in the opposite direction during the past
      20 years. Clinical Neuropsychology, as a specialty, has established training and
      practice guidelines, and more recently, produced an integrated model of education
      and training, not unlike the models developed by medicine and its specialties.
      Nevertheless, there are pressures within the field of Psychology in general, and
      Clinical Neuropsychology in particular, to abrogate standards and weaken
      credentials. These pressures are seen as stemming from prioritizing the interests
      of the practitioner over the needs of the patient and the profession. The thesis
      is presented that upholding standards leads to the benefit of the patient and the
      long-term health of the profession.

PMID- 10937644
TI  - Predictive power of frontal lobe tests in the diagnosis of attention deficit
      hyperactivity disorder.
AB  - A battery of tests presumed to assess various frontal lobe functions in children
      was evaluated for the accuracy of the tests in classifying children as having
      attention deficit hyperactivity disorder (ADHD). Two groups of children were
      tested: (1) 66 children, ages 6-11 years, with ADHD, and (2) a normal community
      control group of 64 children of the same age. Results indicated good positive
      predictive power (PPP) for seven of the tests (ranging from 80 to 90%),
      suggesting that abnormal scores on these tests may be indicative of the presence
      of ADHD. However, the rates of negative predictive power (NPP) even for these
      seven tests were modest (ranging from 50 to 66%). Sensitivity was also poor
      (ranging from 5 to 43%) as were the levels of false negatives (averaging 40%)
      creating fair-to-poor overall classification rates for all tests (49 to 70%). It
      is concluded that while these neuropsychological tests may have some value in
      clinical evaluations of children's psychological abilities, they may not be
      useful as the sole criteria for the diagnostic classification of children as
      ADHD.

PMID- 10937645
TI  - The test for severe impairment: validity with the Dementia Rating Scale and
      utility as a longitudinal measure.
AB  - The Test for Severe Impairment (TSI; Albert & Cohen, 1992) was compared to the
      Dementia Rating Scale (DRS; Mattis, 1988) on nursing home patients identified
      with cognitive impairment. Construct validity, criterion validity, and
      reliability on repeated, longitudinal testing were determined. The TSI was also
      compared with the shortened form of the Boston Naming Test (Mack, Freed,
      Williams, & Henderson, 1992). Results show that the TSI is a valid tool of
      different cognitive domains and is useful in longitudinal settings where repeat
      testing is required. Moreover, although the TSI was a test designed for late
      stage assessment, it is a comparable measure with the DRS and can be used across
      the different levels of cognitive impairment in dementia.

PMID- 10937646
TI  - Adult norms for the Rey-Osterrieth Complex Figure Test and for supplemental
      recognition and matching trials from the Extended Complex Figure Test.
AB  - The Rey-Osterrieth Complex Figure Test ("the Rey"; Osterrieth, 1944; Rey, 1941)
      has accumulated a considerable literature as a test of visual-spatial
      perception/construction and memory. The Extended Complex Figure Test (ECFT;
      Fastenau, 1996a, in press-a; Fastenau & Manning, 1992) supplements the Rey with
      Recognition and Matching trials that follow Copy, Immediate Recall, and Delayed
      Recall. The Rey and ECFT were administered to 211 healthy adults. Age ranged from
      30 years to 85 years (M = 62.9, SD = 14.2), education ranged from 12 years to 25
      years (M = 14.9, SD = 2.6), 55% were women, and over 95% were Caucasian. Age and
      education effects were evident on all trials (Multiple R ranged .23 to .50, p <
      .05), but education explained minimal variance (usually 2-3%) on copy and memory
      trials. Gender effects were negligible, if present. Age-appropriate norms are
      presented using Osterrieth's 36-point scoring, overlapping cells, and convenient
      tables for converting raw scores to scaled scores.

PMID- 10937647
TI  - Information Multiple Choice among healthy older adults: characteristics,
      correlates, and clinical implications.
AB  - Information Multiple Choice (WAIS-R-NI, Kaplan et al., 1991), may be valuable
      when used in conjunction with the standard Information subtest. Due to the
      reduced retrieval demands posed by its recognition format, scores should be even
      less susceptible to neuropathology or normal aging than are those on the standard
      (recall) test, facilitating assessment of premorbid attainment in individuals
      suffering from retrieval-related memory deficits. We provide reliability,
      validity, and normative data on Information Multiple Choice from a sample (N =
      177) of healthy adults aged 50 - 90 years. Information Multiple Choice correlates
      strongly with the standard Information subtest (r = .81) and, as predicted and
      unlike the standard test, does not decline even in very old age. The construct
      validity of Information Multiple Choice is supported, and its clinical utility
      will be enhanced by these normative data.

PMID- 10937648
TI  - Construct validity of the Continuous Recognition Memory test.
AB  - A principal factor analysis was performed on variables derived from a
      neuropsychological battery administered to 100 healthy young adults in order to
      investigate the construct validity of the Continuous Recognition Memory test
      (CRM). It was hypothesized that CRM "hits" and "false alarms" would load on
      different factors. The factors that emerged in the analysis were labeled "Verbal
      Ability", "Divided Attention", "Attention to Visual Detail", "Visuomotor
      Integration and Planning", and "Learning and Memory". As expected, CRM hits had a
      significant loading on the Learning and Memory factor. However, CRM false alarms
      did not have a significant loading on the Divided Attention factor as expected
      and, instead, loaded significantly on the Attention to Visual Detail factor. A
      second analysis was performed using variables from the delayed condition of the
      memory measures. In this analysis, the CRM delayed recognition variable had
      significant loadings on both a "Nonverbal Memory" factor and a "Verbal Memory"
      factor. These analyses support the construct validity of CRM hits as a measure of
      learning and memory and suggest that false alarms provide a measure of attention
      to visual detail.

PMID- 10937649
TI  - Geriatric performance on the Benton Visual Retention Test: demographic and
      diagnostic considerations.
AB  - We examined relationships between demographic and diagnostic variables and Benton
      Visual Retention Test performance in older adults aged 55 to 97 years. We derived
      extended geriatric norms for BVRT total number correct scores adjusted for
      variables that contributed significantly to the variance. We also investigated
      BVRT performance in two commonly presenting diagnostic groups: (1) normal adults
      with memory concerns, and (2) a group with mixed neurologic disorders. Age and
      education but not gender were significantly associated with BVRT performance in
      both normals and normals with memory concerns. Level of cognitive deficit was a
      moderating factor in that age and education also contributed significantly to the
      BVRT performance of no/low deficit neurologic patients but had no impact in
      patients whose cognitive deficits were moderate/severe.

PMID- 10937650
TI  - Language functions in patients with multiple sclerosis.
AB  - Few studies have demonstrated language impairment in patients with multiple
      sclerosis (MS) compared to healthy controls. The purpose of this investigation
      was to examine language functions, specifically naming, comprehension, and verbal
      fluency, in patients with MS and healthy controls to (1) determine if patients
      with MS demonstrate language impairment, and (2) provide clarification of MS
      related language disturbance, particularly in patients with MS of differing
      courses. Results showed that both chronic-progressive and relapsing-remitting
      patients with MS performed significantly more poorly than controls on naming,
      aural comprehension, letter fluency, and category fluency, as well as other
      language-based cognitive measures. Chronic-progressive patients obtained
      significantly lower scores than relapsing-remitting patients on the latter three
      tests. The language disturbance in this MS sample may be partly explained by
      impairment in other verbal cognitive functions. These findings highlight the
      importance of assessing language abilities in patients with MS.

PMID- 10937651
TI  - Comparison of linear equating and prorated short forms for estimating WAIS-R FSIQ
      in a neuropsychological population.
AB  - Comparisons were made of estimates of the Wechsler Adult Intelligence Scale -
      Revised Full Scale IQ using the two-,three- and four-subtest linear equating
      procedures of Kaufman (1990) and Booker and Cyr (1986) with FSIQ estimates using
      prorating to obtain FSIQ scores. The advantage of prorating is that it affords
      greater clinical flexibility in selection of subtests. The participants were 64
      neuropsychiatric patients who completed the full WAIS-R from which short form and
      FSIQ were calculated. Prorating yielded estimates of mean IQ and categorization
      of IQ comparable to IQs obtained by linear equating, though there was an
      increased likelihood of disparate results with extreme IQ scores. Prudent
      clinical judgment is recommended for situations involving unusual or extreme
      scaled score patterns, particularly when the number of subtests is small.

PMID- 10937652
TI  - P300 as an index of recognition in a standard and difficult match-to-sample test:
      a model of amnesia in normal adults.
AB  - Earlier research has supported the use of a P300 (P3)-based procedure to detect
      simulated amnesia. In the present experiment, an attempt was made to model the
      behavior and event-related potentials (ERPs) that amnestic patients might
      demonstrate with relatively easy recognition memory tests, by increasing the
      difficulty of a match-to-sample recognition memory test taken by 18 memory
      unimpaired undergraduates. None of the participants in the modeled amnesic
      condition were classified as having intact recognition memory as the result of P3
      based intra-individual tests (specificity = 100%). The results support the
      utility of a P3 procedure for the detection of malingering by demonstrating the
      procedure to be a valid measure of impaired recognition with this model of
      amnesia.

PMID- 10937653
TI  - Factor structure of the Neurobehavioral Cognitive Status Exam (COGNISTAT) in
      healthy, and psychiatrically and neurologically impaired, elderly adults.
AB  - This study reports the results of factor analyses of COGNISTAT (NCSE) in a sample
      of elderly persons comprised of "healthy" participants with no psychiatric or
      neurological impairments (n = 153), individuals with psychiatric impairments (n =
      70), and those with neurological impairments (n = 80). Our findings support a
      unitary factor structure for COGNISTAT, though a separate factor of unclear
      clinical or theoretical significance was suggested.

PMID- 10937654
TI  - One more test of malingering?

PMID- 10937655
TI  - Developmental psychobiology: a look back on 30 years.
AB  - Developmental Psychobiology publishes papers from the disciplines of psychology,
      biology, neuroscience, and medicine that contribute to an understanding of
      behavioral development. Research focuses on development in the embryo/fetus,
      neonate, juvenile, and adult as well as multidisciplinary research that relates
      behavioral development to anatomy, physiology, biochemistry, genetics, and
      evolution. The journal represents a broad phylogenetic perspective on behavioral
      development by including studies on invertebrates, fish, birds, non-human
      primates, and humans. This paper presents an analysis of empirical articles
      published since its first issue in 1968. This analysis covers number of authors,
      sex of first author; evidence of grant support, and participation of
      investigators from outside the US. Additionally, the analysis includes the topic
      of research, level of analysis, and subject of experimental study. Over its 32
      year history, Developmental Psychobiology has published papers on a wide range of
      topics representing a broad phylogenetic perspective with a continued focus on
      behavioral investigation. This analysis revealed trends such as an increase in
      the number of studies at a physiology/anatomy level, an increase in studies with
      human subjects, and increases in contributions from investigators outside of the
      United States as well as women.

PMID- 10937656
TI  - Development of dustbathing behavior sequences in the domestic fowl: the
      significance of functional experience.
AB  - The development of the sequential structure of dustbathing bouts was studied in
      domestic egg-layer chicks from hatching until 23 days of age using a first order
      Markov chain model analysis. Chicks were reared either with access to sand ("sand
      chicks ") or on a wire floor ( "wire chicks"). All chicks in both groups
      developed a basic structure of the elements pecking, bill raking, ground
      scratching, vertical wingshaking, head rubbing, and side rubbing. Nonetheless,
      there was more cohesion in the bouts of sand chicks than in those of wire chicks:
      wire chicks had more pauses in their bouts and performed more elements while
      standing; also, allopecking (feather-pecking) and preening were incorporated into
      their bouts. We conclude that the basic structure of dustbathing bouts develops
      even in the absence of functional experience with feedback from sand. However,
      absence of normal feedback can lead to problems consisting of interruptions and
      feather-directed behavior.

PMID- 10937657
TI  - Asymmetrical hatching behaviors influence the development of postnatal laterality
      in domestic chicks (Gallus gallus).
AB  - Lateralized motor behaviors have been reported in some avian species. For
      instance, footedness has been reported in parrots and domestic chicks, and
      turning biases have been reported in such species as quail and domestic chicks.
      This study examined the effects of asymmetrical hatching behaviors on the
      development of lateralized turning bias and footedness in domestic chicks.
      Asymmetrical hatching behaviors are counter-clockwise full body turns that many
      precocial birds make to escape the egg. To study the role of such coordinated
      prenatal motor behaviors in the development of lateralization, hatching behaviors
      were systematically disrupted following pipping. Subjects were subsequently
      tested on two measures of laterality: footedness and turning bias. Results
      indicated a significant reduction in individual and group lateralization for both
      measures. These findings suggest that the hatching behaviors found in domestic
      chicks serve to induce the development of strong motor biases at both the
      individual and population level.

PMID- 10937658
TI  - A further characterization of alpha-2 adrenoceptor involvement in the rough-and
      tumble play of juvenile rats.
AB  - In order to further understand the extent to which alpha-2 adrenoceptors are
      involved in play behavior, a more detailed behavioral assessment was made of the
      effects of the alpha-2 agonist clonidine and the alpha-2 antagonist RX821002 on
      the rough-and-tumble play of juvenile rats. Clonidine reduced overall levels of
      playfulness, as indicated by fewer attacks directed to the nape, a lower
      probability of rotating completely to supine in response to nape attacks and
      fewer pins. In contrast, RX821002 increased playfulness, as indicated by more
      attacks directed to the nape, a higher probability of rotating completely to
      supine in response to nape attacks and more pins. Testing rats in an unfamiliar
      environment did not affect the ability of RX821002 to increase play. Abruptly
      turning on a bright light during an ongoing play session also did not affect the
      ability of RX821002 to increase play or the ability of clonidine to reduce play.
      These data suggest that alpha-2 noradrenergic compounds do not affect play by
      altering levels of distractibility. However, the extent to which RX821002 and
      clonidine influenced overall activity during a play bout was compromised by
      turning on a bright light. While this pattern of results is consistent with a
      presynaptic site of action for alpha-2 involvement in modulating overall activity
      during a play bout, the same cannot be concluded about any putative explanatory
      mechanism for alpha-2 involvement in play behavior

PMID- 10937659
TI  - A cholecystokinin receptor antagonist blocks milk-induced but not maternal
      contact-induced decrease of ultrasonic vocalization in rat pups.
AB  - The role of cholecystokinin (CCK) in reducing separation-induced ultrasonic
      vocalization (USV) was examined by peripheral administration (of the selective
      CCK(A) receptor antagonist devazepide to 10-11-day-old rats. Pups placed alone
      for 2 min emitted a mean of 55.1 USV/min. When placed on a paper towel wet with
      warm, sweet milk, USV rate decreased to 23.2/min for the following 8 min.
      Devazepide (150-600 microg/kg IP) prevented this USV reduction, but did not
      increase feeding. In contrast, USV reduction produced by contact with the
      anesthetized dam was not affected by devazepide. Similarly, the opiate antagonist
      naltrexone (0.5 and 1.0 mg/kg) has been shown to block morphine-induced USV
      decrease in pups away from the dam, but was ineffective when USV reduction was
      induced by the presence of the dam (Blass et al., 1990; Carden & Hofer, 1990).
      The current findings suggest that CCK's role is specific, in that it mediates
      milk- but not dam-induced quieting of USV. The results, however, are not
      incompatible with the possibility that CCK and opioids are part of multiple,
      redundant pathways that mediate the quieting of USV by the dam.

PMID- 10937661
TI  - Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha) from Australian
      dasyatid and rhinobatid rays.
AB  - Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha: Eutetrarhynchidae)
      is described from the spiral valves of the rays Rhinobatos typus (Rhinobatidae)
      and Himantura fai (Dasyatidae) from Heron Island, Queensland, Australia. The new
      species is distinguished from all congeners by the deltoid microtriches covering
      the anterior 80% of the scolex and the presence of a dorsoventrally elongate
      genital atrium. The species occurred in the anteriormost section of the spiral
      valve of R. typus. The orientation of the armature of this and other congeners is
      such that principal rows of hooks begin on the bothridial surface of the tentacle
      and end on the antibothridial surface.

PMID- 10937660
TI  - Developmental changes in heart period and high-frequency heart period variability
      from 4 months to 4 years of age.
AB  - Cardiac measures of heart period and high-frequency heart period variability are
      increasingly employed as dependent variables in studies of social and emotional
      development in infancy and childhood. This study describes significant
      developmental increases in these measures in a longitudinal sample assessed at 4,
      9, 14, 24, and 48 months of age. In addition, developmental changes in the
      characteristics of the heart period power spectra are described. These changes
      have implications for the quantification of high-frequency heart period
      variability in infancy and childhood. First, shorter analysis epoch lengths may
      be used for younger infants. Second, the commonly used high-frequency band for
      infants (0.24-1.04 Hz) appears to reach its practical limit at an age of around
      four years. Findings are discussed in relation to the design of developmental
      psychophysiological studies.

PMID- 10937662
TI  - Molecular and morphological differentiation between species of the Plagiorchis
      vespertilionis group (Digenea, Plagiorchiidae) occurring in European bats, with a
      re-description of P. vespertilionis (Muller, 1780).
AB  - The taxonomic history of the species of Plagiorchis Luhe, 1899 occurring in
      European bats has been very confused because of high morphological similarity
      between different forms/species and the inadequate initial description of P.
      vespertilionis (Muller, 1780). As morphological data alone have not provided
      enough convincing arguments to solve the problem, the sequences from the nuclear
      rDNA ITS region (ITS1, 5.8S and ITS2) of three species of the P. vespertilionis
      group (P. vespertilionis, P. muelleri Tkach & Sharpilo, 1990 and P. koreanus
      Ogata, 1938) occurring in European bats were used to test the validity of these
      species and evaluate some of the morphological characters used for the species
      differentiation within this group. P. elegans from birds was used as the outgroup
      in the analysis. All three ingroup species were clearly distinguishable using ITS
      sequences. Among them, P. koreanus occupied a basal position, while P.
      vespertilionis and P. muelleri appeared as a cluster of two closely related,
      derived species. ITS sequences of the specimens obtained from different hosts
      and/or geographical areas did not exhibit any intraspecific variability.
      Morphological study of the material in collections revealed characters which
      enable the species of Plagiorchis from bats in Europe to be distinguished. Taking
      into account that the type-material of P. vespertilionis. described during the
      18th Century, has been lost, for nomenclatural stability, a neotype is
      established and described. An amended description of the type-material of P.
      muelleri and keys for the determination of Plagiorchis spp. from European bats
      are presented.

PMID- 10937663
TI  - [Wardium longosacco (Joyeux & baer, 1939) n. comb. (Cestoda: Hymenolepididae)
      parasite of Charadrius marginatus (Aves: Charadrii) of South Africa].
AB  - The authors describe and illustrate Wardium longosacco (Joyeux & Baer, 1939) n.
      comb. (Cestoda: Hymenolepididae) collected from Charadrius marginatus from South
      Africa. The species with a strobila 7 cm long is characterised by one crown of
      ten aploparaksoid hooks 27-30 microm long, a simple genital atrium, a long
      evaginated cirrus (120 microm) which is glabrous, regularly cylindrical and
      slender (12-6.5 microm in diameters) and a simple, tubular, membranous vagina.
      The species Hymenolepis clandestina sensu Deblock (1964) nec (Krabbe, 1869) is a
      synonym of W. longosacco (Joyeux & Baer, 1939) n. comb.

PMID- 10937664
TI  - Leiperia cincinnalis Sambon, 1922 (Pentastomida) from Nile crocodiles Crocodylus
      niloticus in the Kruger National Park, South Africa, with a description of the
      male.
AB  - A single male and several adult females of the pentastomid Leiperia cincinnalis
      were recovered from the trachea of five of six Nile crocodiles examined in 1995
      and 1998. Infective larvae, pre-adult males and females, as well as mature males,
      occurred in clusters in the pulmonary artery but infective larvae and pre-adult
      females were also occasionally taken from the lungs. Irrespective of the
      developmental stage, the intensity of infection was 3, 6, 48, 72 and 79. Sixty
      four percent of eggs recovered from the posterior part of the uterus of a patent
      L. cincinnalis female contained fully-developed primary larvae and these were
      used to infect 24 Mozambique bream Oreochromis mossambicus. Within a week of
      infection all the fish died and hatched primary larvae were recovered from the
      stomach and anterior part of the intestine. Eggs that had not hatched were found
      to be unsegmented. The total primary larval count in seven fish was 18, 12, 1,
      25, 16, >40 and >50. Descriptions with detailed measurements are given of the
      females, the males, the eggs, the primary larvae and the infective larvae of L.
      cincinnalis.

PMID- 10937665
TI  - New species of the Monocotylidae (Monogenea) from the stingray Dasyatis tortonesi
      Capape (Euselachii, Dasyatidae) off the Tunisian coast, with comments on host
      specificity and the specific identities of Mediterranean stingrays.
AB  - Heterocotyle capapei n. sp. and Thaumatocotyle tunisiensis n. sp. are described
      from the gills and the nasal cavity, respectively, of Dasyatis tortonesi
      collected from the Tunisian coast. H. capapei is distinguished from other species
      in the genus by the morphology of the penis, which is conical and has a long
      narrow distal point. T. tunisiensis differs from all known species of
      Thaumatocotyle by the shape and size of the penis. The host Dasyatis tortonesi
      has long been confused with D. pastinaca. Our study shows that their monogeneans
      are oioxenic, suggesting that D. pastinaca and D. tortonesi are distinct species.
      These results suggest that the monogenean parasite fauna could be used as a
      diagnostic tool for species identification: these parasites may, therefore,
      represent good biological indicators. The host-specificity of the Heterocotylinae
      and Merizocotylinae is discussed.

PMID- 10937666
TI  - Polylekithum percai n. sp. (Trematoda: Allocreadiidae) from Percichthys trucha
      (Perciformes: Percichthydae) in Patagonia, Argentina, and a redescription of
      Homalometron papilliferum (Szidat, 1956) n. comb.
AB  - Two species of Digenea are recorded from the intestine of Percichthys trucha
      (Percichthydae) from Patagonian water bodies. Polylekithum percai n. sp.
      (Allocreadiidae) is distinguished by its body size, the relative size of the
      suckers, the anterior extension of the vitelline fields, the number of eggs in
      the uterus and the different species of fish host from the two previously
      described species of Polylekithum. Homalometron (= Austrocreadium) papilliferum
      (Szidat, 1956) n. comb. is redescribed. Due to its spined tegument and the
      absence of a cirrus-sac, this species is considered a member of the family
      Apocreadiidae.

PMID- 10937668
TI  - A new species of larval Dasitrombium Zhang, 1994 (Acari: Prostigmata:
      Neothrombiidae) parasitic on grasshoppers from Nicaragua.
AB  - A new species of larval neothrombids, Dasitrombium clarissae (Acari: Prostigmata:
      Neothrombiidae), parasitic on grasshoppers from Nicaragua is described. Larvae
      have the following diagnostic features: Ta I 110-114, Ti I 48-52, Ta II 102-106,
      Ti II 44-48, Ip 1020-1054, ratio L/W 1.29-1.40, and the presence on genu I of
      only two solenidia.

PMID- 10937667
TI  - Isospora lutrae n. sp. (Apicomplexa: Eimeriidae), a new coccidium from the
      European otter Lutra lutra (L.) (Carnivora: Mustelidae) from Spain.
AB  - Parasitological examination of European otter originating from Extremadura, Spain
      revealed the presence of a new isosporan species. Oocysts of Isospora lutrae n.
      sp. are spherical to subspherical, 31.2 (27.5-32) x 29.6 (28-31) microm and have
      a smooth wall c. 1 microm thick. Sporocysts are ellipsoidal, 18.2 (17-19) x 14.4
      (14-16) microm and lack Stieda and substieda bodies. A spherical sporocyst
      residuum is present, consisting of granules scattered among the sporozoites.
      Sporozoites are spindle-shaped, 12.4 x 2.5 microm and have anterior and posterior
      refractile bodies. Based on its unique morphologic structure and host, I. lutrae
      is considered to be new.

PMID- 10937669
TI  - A new canestriniid mite, Bircericola bertrami n. g., n. sp. (Acari: Astigmata:
      Canestriniidae), parasitic on tenebrioniid beetles (Coleoptera: Tenebrionidae)
      from Tunisia.
AB  - The new genus Bircericola (Acari: Astigmata: Canestriniidae) and new species
      Bircericola bertrami from undetermined tenebrioniid beetles from Tunisia are
      described. Diagnostic features include: dorsal integument covered by longitudinal
      lines; suture separating propodosoma from hysterosoma present; male adanal
      suckers well developed; two pairs of paranal setae in males and six pairs in
      females; tarsi I-II very short (< 30 microm); and solenidia delta I and delta II
      subequal in length to setae cG I and cG II, respectively.

PMID- 10937670
TI  - A redescription of Pintneriella Yamaguti, 1934 (Cestoda: Trypanorhyncha and an
      examination of its systematic position.
AB  - Specimens of Pintneriella musculicola Yamaguti, 1934 are redescribed based on
      paratype material and specimens subsequently allocated to the species by its
      describer. The cestode species is characterised by two bothridia, a typical
      heteroacanthous armature with a distinctive basal swelling and basal armature, a
      space between hook files 1 and 1', nine hooks per principal row, no intercalary
      hooks and bands of hooklets or chainettes but a distinctive space on the external
      surface of the tentacle between hook files 9 and 9'. The strobilia is unknown.
      The features described indicate that Pintneriella is a valid genus within the
      Heteracanthoidea. Its currently known morphological features do not allow its
      allocation to an existing family.

PMID- 10937671
TI  - Perihepatic lymphadenopathy in chronic liver diseases.

PMID- 10937672
TI  - Understanding the molecular changes in Barrett's oesophagus.

PMID- 10937673
TI  - Dendritic cell-based cancer immunotherapy: potential for treatment of colorectal
      cancer?
AB  - Human tumours including those of the gastrointestinal tract express a number of
      specific antigens that can be recognized by T cells, thus providing potential
      targets for cancer immunotherapy. Dendritic cells (DC) are rare leucocytes that
      are uniquely potent in their ability to capture, process and present antigens to
      T cells, and so selectively migrate through tissues to reach lymph nodes and
      spleen where initiation of immune responses takes place. Studies in murine tumour
      models have shown clearly that DC are capable of presenting tumour antigens to
      initiate tumour-specific cytotoxic T cell responses, and DC vaccination can
      induce anti-tumour activity against both primary tumours and pre-established
      tumour metastases. These findings together with the ability to culture sufficient
      numbers of DC from human bone marrow or blood progenitors have prompted the
      current major interest in their potential use in human tumour vaccination.
      Vaccine production involves harvesting autologous DC from cultured peripheral
      blood mononuclear cells in the presence of a cocktail of cytokines, ex vivo
      exposure of the DC to tumour antigens and return of pulsed DC to the patient to
      induce tumour immunity. Reports from Phase I/II clinical trials indicate that DC
      vaccines are safe with little or no side effect, and are capable of initiating
      antigen-specific T cell responses. Furthermore, defined tumour antigens are not
      necessarily required, which may make the process more applicable to human
      cancers, including many gastrointestinal cancers that lack well-characterized
      tumour-specific antigens. Additional trials of DC vaccination for a variety of
      human cancers including colorectal cancers are under way, and refinement of
      vaccine protocols and methods for targeting tumour antigens to DC in vivo are
      also being explored. There is reason to believe that DC-based vaccination could
      become an adjunct to current treatments for human cancers including colorectal
      cancer in the foreseeable future.

PMID- 10937674
TI  - Branched-chain amino acids.
AB  - The branched-chain amino acids (BCAA), isoleucine, leucine and valine, are unique
      in that they are principally metabolized extrahepatically in the skeletal muscle.
      This observation led to the investigation of these nutrients in a number of
      clinical scenarios. By far the most intensively studied applications for BCAA
      have been in patients with liver failure and/or patients in catabolic disease
      states. However, the resulting studies have not demonstrated a clear clinical
      benefit for BCAA nutritional supplements. In patients with liver failure, the
      BCAA did improve nitrogen retention and protein synthesis, but their effect on
      patient outcome was less clear. Similarly, in critically ill septic patients,
      BCAA did not improve either survival or morbidity. The BCAA are important
      nutrients, and it seems that any specific benefits associated with their use will
      be based upon a greater understanding of the underlying cellular biology.
      Potential areas of further research may include the combination of BCAA
      supplements with other anabolic factors (e.g. growth hormone) in managing
      patients with catabolic disease states.

PMID- 10937675
TI  - Reactive oxygen and mechanisms of inflammatory liver injury.
AB  - Reactive oxygen species (ROS) are important cytotoxic and signalling mediators in
      the pathophysiology of inflammatory liver diseases. They can be generated by
      resident and infiltrating phagocytes and/or intracellularly in every liver cell
      type after stimulation with cytokines. Although ROS are able to cause cell
      destruction by massive lipid peroxidation, in most cases, ROS are more likely to
      modulate signal transduction pathways by affecting redox-sensitive enzymes,
      organelles (e.g. mitochondria) and transcription factors. Thus, ROS can directly
      induce and/or regulate apoptotic and necrotic cell death. In addition, ROS can
      have indirect effects on the pathophysiology by supporting protease activity
      through inactivation of antiproteases and by modulating the formation of
      inflammatory mediators and adhesion molecules. Many of the effects of ROS may
      occur simultaneously or sequentially in the pathophysiology. Although mainly
      described in this review as detrimental, ROS are essential for host-defence
      functions of phagocytes and can modulate the formation of mediators involved in
      regulating sinusoidal blood flow and liver regeneration. Thus, continuous efforts
      are necessary to improve our understanding of the role of ROS in the
      pathophysiology of inflammatory liver diseases and to discover therapeutic
      interventions that selectively target the negative effects of reactive oxygen
      formation.

PMID- 10937676
TI  - Use of tamoxifen in hepatocellular carcinoma: a review and paradigm shift.
AB  - Hepatocellular carcinoma is often diagnosed at a late, inoperable stage for which
      there are no uniformly efficacious treatment available presently. The oral anti
      oestrogen drug, tamoxifen, has been used in such patients, based on the belief
      that the growth of hepatocellular carcinoma is promoted by endogenous oestrogen
      via a receptor-mediated process. In this review, we examine the trials reported
      in the literature using tamoxifen in hepatocellular carcinoma. Randomized
      controlled trials with tamoxifen have so far revealed mixed results. We propose
      that this may be due to the fact that the mechanism of action of tamoxifen in
      hepatocellular carcinoma is via an oestrogen-receptor independent pathway that
      requires much higher doses of tamoxifen for activation than those used in the
      trials so far. Thus there must be a paradigm shift to dissociate the action of
      tamoxifen from oestrogen receptors in hepatocellular carcinoma. This means that
      future trials with tamoxifen in hepatocellular carcinoma should use higher doses
      of tamoxifen, at least four to eight-fold that of the dose that is efficacious in
      an oestrogen-receptor dependent mechanism.

PMID- 10937677
TI  - K-ras codon 12 mutations in Barrett's oesophagus and adenocarcinomas of the
      oesophagus and oesophagogastric junction.
AB  - BACKGROUND: Activation of the ras oncogene is commonly found in gastrointestinal
      tract cancers, but the role of ras in the development and progression of
      Barrett's oesophagus and associated cancers is uncertain. METHODS: The frequency
      of K-ras codon 12 point mutations was assessed in 52 paraffin-embedded tissues
      from 44 patients with oesophageal pathology. The specimens were classified
      pathologically as follows: adenocarcinoma of the oesophagus or oesophagogastric
      junction (n = 23), Barrett's high-grade dysplasia (n = 5), low-grade dysplasia (n
      = 14), intestinal metaplasia (n = 4), normal oesophagus (n = 5) or normal stomach
      (n = 1). DNA was extracted from three consecutive sections of each paraffin block
      and mutations at bases 1 and 2 of K-ras codon 12 were identified using a novel
      restriction endonuclease-mediated selective polymerase chain reaction method.
      RESULTS: Mutations were found in 7 of 23 (30.4%) adenocarcinomas and in 2 of 5
      (40%) high-grade dysplasia specimens. No mutations were found in specimens of low
      grade dysplasia, intestinal metaplasia without dysplasia, or normal oesophagus
      and stomach. There were no significant associations between the presence of
      mutations and clinicopathologic features in the patients with cancer. One patient
      who progressed from low-grade to high-grade dysplasia was found to have developed
      mutant K-ras in the course of this transformation. CONCLUSION: These results
      suggest that K-ras codon 12 mutations may occur frequently in patients with
      Barrett's oesophagus with high-grade dysplasia or adenocarcinoma of the
      oesophagus or oesophagogastric junction. K-ras mutation may be a late event in
      the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.

PMID- 10937678
TI  - A topographic study of Helicobacter pylori density, distribution and associated
      gastritis.
AB  - BACKGROUND AND AIMS: The topographic distribution and density of Helicobacter
      pylori and associated gastritis in the stomach were studied in order to determine
      which biopsy sites are likely to provide the maximum yield so as to reduce the
      fallacious results due to sampling error. METHODS: Fifty patients with upper
      gastrointestinal symptoms were studied. Eleven gastric biopsies from
      predetermined sites were obtained and subjected to ultra-rapid urease test,
      imprint cytology and histology. Haematoxylin and eosin stain was used for
      defining gastritis and other associated histopathological details. Loeffler's
      methylene blue stain was used to confirm the presence of H. pylori in imprint
      smears and histological sections. RESULTS: All 50 patients had H. pylori
      infection and evidence of chronic gastritis at one or more of the 11 biopsy
      sites. Maximum and minimum percentage positivity were observed at A3 (antral
      lesser curvature) and B4 (corpus greater curvature), respectively. Various sites
      in decreasing order of percentage positivity were A3 > A2 > A1 > A4 > B3 > B1 >
      A5 > B6 > B5 > B2 > B4. Among the biopsies obtained from the corpus, B3 (corpus
      lesser curvature) was the site with maximum positivity. A3 and B4 had a
      statistically significant difference in percentage positivity (P < 0.0001) for H.
      pylori and gastritis. The maximum and minimum density scores of H. pylori and
      gastritis were found in A3 and the B4, respectively. A3 had a significantly
      higher (P < 0.0001) mean density score than any other site in the stomach. The
      difference in the grading of H. pylori between A3 and B3 (sites of maximum
      positivity in antrum and corpus) was statistically significant (P < 0.0001). A
      statistically significant (P < 0.001) positive correlation between increasing
      grades of H. pylori and gastritis was observed at the site of maximum density.
      Eighty per cent of the patients had antral predominant gastritis and in 82%, H.
      pylori was predominantly observed in antral biopsies. CONCLUSION: It is concluded
      that two biopsies taken from A3 are sufficient for confirmation of presence of H.
      pylori and associated gastritis for initiation of treatment. However, additional
      biopsies from B3 will help in deciding the topographic pattern of gastritis.

PMID- 10937679
TI  - Expression of human telomerase catalytic subunit gene in cancerous and
      precancerous gastric conditions.
AB  - BACKGROUND AND AIMS: Telomerase activity is thought to be necessary for cellular
      immortality and carcinogenesis. The mRNA that encodes the telomerase catalytic
      subunit (hTERT) has recently been identified, and expression of hTERT mRNA is
      thought to regulate activation of telomerase. To determine at what stage of
      carcinogenesis cells begin to express hTERT, we analysed hTERT mRNA expression in
      gastric carcinoma and precancerous conditions, focusing on chronic gastritis with
      or without intestinal metaplasia. METHODS: Using reverse transcription-polymerase
      chain reaction, hTERT gene expression was investigated in 18 gastric cancers and
      60 specimens of chronic gastritis. Telomerase activity was evaluated using
      telomeric repeat amplification protocol. RESULTS: Sixteen of 18 (89%) gastric
      carcinomas expressed hTERT mRNA, and this expression was unrelated to
      histological type or depth of invasion. Telomerase activity was found in seven of
      eight (88%) gastric cancer tissues, all of which expressed hTERT mRNA. Expression
      of hTERT mRNA was positive in 14 of 60 (23%) specimens of chronic gastritis, and
      was most prominent in seven of 15 (47%) specimens of gastric mucosa with
      intestinal metaplasia. Expression of the hTERT gene was significantly more
      frequent in chronic gastritis with intestinal metaplasia than in gastritis
      without intestinal metaplasia (P=0.030). In addition, hTERT gene expression was
      not correlated with age, sex, biopsy site, histological grade of inflammatory
      cells, glandular atrophy and lymph follicles, or infection with Helicobacter
      pylori. None of eight normal gastric mucosa expressed hTERT mRNA. CONCLUSIONS:
      Our results indicate that hTERT mRNA is expressed in precancerous conditions as
      well as in gastric cancer, and that hTERT gene expression is induced at an early
      stage of gastric carcinogenesis.

PMID- 10937681
TI  - Risk of gastric cancer is not increased after partial gastrectomy.
AB  - BACKGROUND: It has been suggested that there is an increased risk of gastric
      cancer following partial gastrectomy. This question has not been studied in an
      Australian population. METHODS: The records of a total of 569 patients who had a
      partial gastrectomy for peptic ulcer disease at Repatriation General Hospital,
      Heidelberg, between 1957 and 1976 were reviewed. All were followed to date of
      death or 31 December 1996. The expected rate of gastric cancer for this
      population was estimated from published Australian age-and sex-specific gastric
      cancer mortality rates over this period, and a standardized incidence ratio was
      calculated. RESULTS: The mean age at surgery was 53.5 years (range 27-83 years).
      There were 547 male (96.4%) and 22 female (3.6%) patients. Five hundred and seven
      (83.5%) had a Billroth II procedure. Thirty-eight patients (6.3%) were lost to
      follow up and were not included in the analysis. From the records of the
      Department of Veterans' Affairs, it was established that 125 (20.6%) were alive
      in December 1996, a mean survival after surgery of 18.8 years. The mean
      documented duration of follow up was 17.3 years (range 1-41 years). Nine patients
      developed cancer in the gastric remnant. The expected number of cancers in this
      population was 6.5. Assuming all survivors were free of gastric cancer, the
      standardized incidence ratio was 1.39 (95% confidence intervals 0.64-2.65,
      P=0.313). CONCLUSION: The risk of gastric cancer was not increased after partial
      gastrectomy in this Australian population.

PMID- 10937680
TI  - Cyclo-oxygenase-2 inhibitors suppress epithelial cell kinetics and delay gastric
      wound healing in rats.
AB  - BACKGROUND AND AIMS: The present study examined the effects of NS-398, a specific
      cyclo-oxygenase-2 inhibitor, on gastric mucosal cell kinetics and gastric wound
      healing following acid-induced injury. METHODS: Male Sprague-Dawley rats were
      fasted for 24 h and then 0.6 mol/L hydrochloric acid (HCl; 1 mL) was administered
      into the stomach; NS-398 or indomethacin was administered to the animals 10 min
      after the acid. Levels of constitutive cyclo-oxygenase (COX-1) and mitogen
      inducible cyclo-oxygenase (COX-2) in the gastric mucosa were analysed using
      western blotting and immunohistochemical staining. The grade of the lesion was
      assessed using planimetry and histological examination, including
      immunohistochemistry for proliferating cell nuclear antigen (PCNA). RESULTS:
      Although there was strong expression of COX-1, there was minimal expression of
      COX-2 in the gastric mucosa. Expression of COX-2 was enhanced mainly in surface
      epithelial cells and neck cells following HCl administration. Gastric mucosal
      ulcers and erosions healed within 48 h, during which time the proliferative zone
      expanded in the control animals. Indomethacin and NS-398 suppressed the expansion
      of the proliferative zone and delayed the healing of the gastric injury.
      CONCLUSION: The present study demonstrated that cyclo-oxygenase-2 inhibitors
      delay gastric wound healing by suppressing expansion of the mucosal proliferative
      zone. These results provide evidence that cyclo-oxygenase-2 has an important role
      in gastric mucosal regeneration.

PMID- 10937682
TI  - Enhanced tumorigenicity of insulinoma by X-irradiation of the gastric regions in
      Sprague-Dawley male rats.
AB  - BACKGROUND AND AIMS: There has been no suitable animal model for human insulinoma
      because incidence of pancreatic tumours induced by whole-body irradiation or
      chemicals has been very low. The purpose of this study was to establish an
      experimental model with a high incidence of insulinoma. The induction of islet
      cell tumour by X-irradiation was investigated. METHODS: Forty Sprague-Dawley male
      rats were used in this study. Twenty-eight rats were irradiated with two 10-Gy
      doses to the gastric region at a 3-day interval, and 12 rats not subjected to X
      irradiation served as a control group. The rats were killed 16 months after the
      first irradiation. Expression of insulin mRNA and protein was examined by
      northern blot analysis and immunohistochemistry, respectively. Rat serum insulin
      and glucose levels were measured using enzyme-linked immunosorbent assay.
      RESULTS: Tumour incidence was 89.3% (25/28) in X-ray group and 8.3% (1/12) in the
      control group (P < 0.05). Pancreatic tumours, which appeared in all 25 rats with
      tumours, showed the highest incidence of all neoplasms detected. Tumour cells
      showed strong immunoreactivity for insulin in 20 of 25 pancreatic tumours (80%).
      Expression of insulin mRNA was confirmed by northern blot analysis. Furthermore,
      rats with pancreatic tumours had lower serum glucose levels and higher insulin
      levels than the control rats. CONCLUSION: X-irradiated SD rats may be considered
      a suitable model for insulinoma because of their high tumorigenicity.

PMID- 10937683
TI  - Association of human leucocyte-DR and DQ antigens in coeliac disease: a family
      study.
AB  - BACKGROUND AND AIMS: No family studies regarding the association of coeliac
      disease with the human leucocyte antigen (HLA)-DQ locus are available. Moreover,
      no HLA studies have been carried out in coeliac disease patients from India. The
      aim of this study was to study the HLA class II (DR and DQ) antigens in children
      with coeliac disease and in their first-degree relatives. METHODS: Fifteen
      children with coeliac disease and their first-degree relatives (birth parents of
      all the coeliac disease patients and fifteen siblings) were studied. A group of
      123 healthy unrelated and ethnically matched subjects were used as controls. The
      HLA-DR and -DQ typing was carried out by a complement-dependent
      microlymphocytotoxicity assay. The transmission disequilibrium test was used for
      analysis of results. RESULTS: There was no association of coeliac disease with DR
      phenotypes. Ninety-three per cent of patients (14/15) carried the DQ2 allele. DQ2
      was transmitted in 15 of 19 informative cases (transmission probability of 79%,
      chi2 6.368 with 1 df, nominal P=0.012 and P value corrected for multiple
      test=0.035). The haplotype relative risk associated with DQ2 was 5.71 (95%
      confidence interval 1.71-16.28). CONCLUSION: Coeliac disease in Indian children
      is predominantly associated with HLA-DQ2.

PMID- 10937684
TI  - Are there any sex differences in fatty liver? A study of glucose metabolism and
      body fat distribution.
AB  - BACKGROUND AND AIMS: Fatty liver is a common condition found more often in males.
      Whether sex differences affect its development is presently unknown. The
      hypothesis that glucose metabolism alterations or central body fat distribution
      are gender-related in fatty liver was investigated. METHODS: Overall 199
      consecutive subjects seen in the Division of Internal Medicine and
      Gastroenterology, Modena City Hospital, were enrolled. In the main arm of the
      present study, 44 men with sonographic fatty liver and 47 controls without, and
      18 women with and 19 without fatty liver had their body mass index (an index of
      overall adiposity), hepatobiliary serum enzymes, serum cholesterol and
      triglycerides determined. All underwent oral glucose tolerance tests (estimated
      through the glucose area under the curve with the trapezoidal method). In the
      ancillary arm study, 17 other men with and 14 without, and 11 other women with
      and 29 without fatty liver had anthropometric measurements of body fat
      distribution (waist/hip, waist/height and skinfold thickness). RESULTS: Following
      statistical evaluation including univariate and multivariate analyses (main
      study), elevated body mass index was found to be an independent predictor of
      fatty liver in either sex. Glucose area under the curve and a central-type body
      fat distribution (ancillary study) predicted FL only in women. CONCLUSIONS: Fatty
      liver could be gender-related in the present series.

PMID- 10937685
TI  - Perihepatic lymphadenopathy in chronic hepatitis C: a complementary diagnostic
      element?
AB  - BACKGROUND AND AIMS: The authors searched for perihepatic lymph nodes during
      ultrasonography performed for other symptoms in 1222 Sicilian outpatients in
      order to assess the incidence and possible significance of the association of
      perihepatic lymph nodes and chronic hepatitis C. METHOD: One or two lymph nodes
      were observed in 184/1222 patients, and 142 of these 184 were anti-hepatitis C
      virus (HCV) positive. RESULTS: Our results confirmed a very high incidence of
      perihepatic lymphadenopathy during chronic hepatitis. The concomitant presence of
      HCV virus and perihepatic lymph nodes may confirm the marked lymphotropism of
      this virus. CONCLUSION: As anti-HCV positivity is frequent in asymptomatic
      subjects with normal alanine aminotransferase concentrations, the authors believe
      that searching for sentinel perihepatic lymph nodes during abdominal
      ultrasonography could be recommended in routine diagnostic screening for HCV
      infection. Any perihepatic lymph nodes detected by this method could pinpoint
      subjects for whom more specific examinations are required, especially in areas
      where the virus is particularly endemic.

PMID- 10937686
TI  - Accumulation of copper in the liver and hepatic injury in chronic hepatitis C.
AB  - BACKGROUND AND AIMS: Relationships between chronic liver disease and trace metals
      have not been clearly understood. To examine connections between severity of
      hepatic fibrosis in chronic hepatitis C and copper, iron and zinc we measured the
      contents of these metals in liver tissue and serum in the patients. METHODS:
      Forty-one patients (26-62 years), 13 with fibrosis representing grade F1, 16 with
      F2, seven with F3, and five with F4, entered this study. Metals were quantified
      in needle liver-biopsy specimens by particle-induced X-ray emission. In serum,
      metals were measured by flameless atomic absorption spectrometry. RESULTS:
      Hepatic copper content increased with progression of hepatic fibrosis (P < 0.05).
      The copper content correlated positively with bilirubin (r = 0.466, P = 0.0023),
      and with type IV collagen (r = 0.402, P = 0.0086) and correlated negatively with
      albumin (r = -0.404, P = 0.080). However, hepatic iron and zinc contents did not
      show a significant differences between grades of fibrosis. CONCLUSIONS: Copper
      accumulation in fibrotic livers caused by chronic hepatitis C may contribute to
      hepatic injury. The real mechanism is not known at present, but excess copper may
      damage the liver by oxidative stress.

PMID- 10937688
TI  - Alcohol consumption induces hepatocyte apoptosis in patients with chronic
      hepatitis C infection.
AB  - BACKGROUND: Epidemiological studies have established that heavy alcohol
      consumption in persons with chronic hepatitis C infection is associated with
      advanced liver disease, including cirrhosis. The cellular mechanisms underlying
      this process, which appear to occur over decades, are unknown. Increased
      hepatocyte apoptosis has been observed in association with hepatitis C infection.
      The aim of this study was to evaluate the relationship between alcohol
      consumption and hepatocyte apoptosis in hepatitis C-infected patients. METHODS:
      Liver tissue from 20 hepatitis C-infected patients with variable alcohol
      consumption, and 10 normal control subjects was examined for hepatocyte
      apoptosis, proliferation and bcl-2 expression. RESULTS: Hepatocyte apoptosis was
      significantly greater in hepatitis C-infected patients than in controls. In
      hepatitis C-infected patients, significantly more hepatocyte apoptosis was seen
      in those consuming at least 30 g per day of alcohol compared with those drinking
      less than 10 g daily. Bcl-2, an inhibitor of apoptosis, was not detected in liver
      tissue from patients with the highest ethanol intake and rate of hepatocyte
      apoptosis. In contrast, patients drinking lesser amounts of ethanol had lower
      rates of hepatocyte apoptosis and more frequent bcl-2 expression. CONCLUSIONS:
      This study confirms that both hepatitis C infection and ethanol consumption
      induce hepatocyte apoptosis in humans. Ethanol-induced hepatocyte apoptosis has
      previously been shown only in animal models of alcohol-related liver injury. The
      precise role of apoptosis in the pathogenesis of hepatitis C-related liver injury
      remains unclear, but its induction may be related to downregulation of bcl-2
      expression associated with ethanol consumption.

PMID- 10937687
TI  - Serotyping and genotyping of hepatitis C virus in Taiwanese patients with type C
      chronic liver disease and uraemic patients on maintenance haemodialysis.
AB  - BACKGROUND: To evaluate a recombinant immunoblot hepatitis C virus (HCV)
      serotyping assay, which determines HCV serotypes 1, 2, and 3 by detecting type
      specific antibodies to core-and NS-4-derived peptides. METHODS: Immunoreactivity
      of type-specific antibodies among 173 chronic hepatitis C patients and 43
      haemodialysis patients in Taiwan was examined and the serotyping results were
      compared with genotyping by Okamoto's method. Serial specimens from 29 patients
      undergoing interferon-alpha therapy were also evaluated. RESULTS: Of the 205
      specimens for which genotyping data were available, 51.2% were of serotype 1,
      31.7% of serotype 2, 1.0% of serotype 3, 2.4% of either serotype 1 or 3, and the
      remaining 13.7% were untypable. The serotypable rate was significantly lower in
      haemodialysis patients than in chronic hepatitis C patients (70.0% vs 94.9%; P <
      0.001). Serotyping of genotype 2b specimens was significantly more dependent on
      core peptide bands than other genotypes. Using genotyping as the reference, the
      overall sensitivity, specificity and concordance of the recombinant immunoblot
      HCV serotyping assay were 86.3%, 97.2% and 83.9%, respectively. However, the
      serotyping assay had significantly lower sensitivity (69.2%), specificity (77.8%)
      and concordance (53.8%) for genotype 2b specimens. Of nine HCV complete
      responders, one lost type-specific antibodies 6 months after the cessation of
      interferon-alpha treatment. CONCLUSIONS: These results suggest that, except for
      less than optimal performance with immunocompromised or genotype 2b patients, the
      HCV serotyping assay is a practical and useful method for HCV typing in the
      clinical setting in Taiwan.

PMID- 10937689
TI  - Images of interest. Gastrointestinal: stromal cell tumours of the stomach.

PMID- 10937690
TI  - Images of interest. Hepatobiliary and pancreatic: a man who underwent local
      ablation therapy for hepatocellular carcinoma.

PMID- 10937691
TI  - Sensory neuropathy in the prodromal phase of hepatitis A and review of the
      literature.
AB  - We report an unrecognized clinical presentation of hepatitis A with unilateral
      peripheral acute sensory loss in the prodromal phase of the illness. Although
      rare, focal neurological signs are known to occur in hepatitis A before, during
      and after the icteric phase; a pure peripheral sensory neuropathy is distinctly
      uncommon. Possible lesions could include radiculopathy of the lower thoraco-lumbo
      sacral dorsal nerve roots or a partial transverse myelitis of Brown-Sequad like
      distribution. The signs and symptoms lasted only a few days and the patient had
      an uneventful recovery.

PMID- 10937692
TI  - Primary sodium plasma membrane ATPases in salt-tolerant algae: facts and
      fictions.
AB  - For thermodynamic reasons algae growing in media of both high salinity and high
      alkalinity require active export of sodium. However, experimental evidence for an
      active Na+-dependent cycle was scarce until recently, in contrast to the
      situation in marine bacteria (including cyanobacteria), fungi and animals.
      However, a review of literature reveals that some progress has been made in this
      respect, recently: data demonstrate that at least in two marine algae,
      Tetraselmis (Platymonas) viridis and Heterosigma akashiwo (syn. Olisthodiscus
      luteus), active Na+-export is carried out by means of a plasma membrane localized
      Na+-pump (apparent molecular mass 100-140 kDa). Biochemical characteristics of
      this vanadate-sensitive, but ouabain-resistant primary P-type Na+-ATPase are
      described and compared with the corresponding properties of Na+-ATPase from
      prokaryotes and animals. Alternative mechanisms for Na+-pumping are discussed.

PMID- 10937693
TI  - Induced activity of adenine phosphoribosyltransferase (APRT) in iron-deficiency
      barley roots: a possible role for phytosiderophore production.
AB  - To isolate the genes involved in the response of graminaceous plants to Fe
      deficient stress, a protein induced by Fe-deficiency treatment was isolated from
      barley (Hordeum vulgare L.) roots. Based on the partial amino acid sequence of
      this protein, a cDNA (HvAPT1) encoding adenine phosphoribosyltransferase (APRT:
      EC 2.4.2.7) was cloned from a cDNA library prepared from Fe-deficient barley
      roots. Southern analysis suggested that there were at least two genes encoding
      APRT in barley. Fe deficiency increased HvAPT1 expression in barley roots and
      resupplying Fe to the Fe-deficient plants rapidly negated the increase in HvAPT1
      mRNA. Analysis of localization of HvAPT1-sGFP fusion proteins in tobacco BY-2
      cells indicated that the protein from HvAPT1 was localized in the cytoplasm of
      cells. Consistent with the results of Northern analysis, the enzymatic activity
      of APRT in barley roots was remarkably increased by Fe deficiency. This induction
      of APRT activity by Fe deficiency was also observed in roots of other
      graminaceous plants such as rye, maize, and rice. In contrast, the induction was
      not observed to occur in the roots of a non-graminaceous plant, tobacco.
      Graminaceous plants generally synthesize the mugineic acid family
      phytosiderophores (MAs) in roots under Fe-deficient conditions. In this paper, a
      possible role of HvAPT1 in the biosynthesis of MAs related to adenine salvage in
      the methionine cycle is discussed.

PMID- 10937694
TI  - Three major somatic embryogenesis related proteins in Cichorium identified as PR
      proteins.
AB  - In Cichorium hybrid clone '474' (C. intybus L., var. sativum x C. endivia L.,
      var. latifolia), the direct somatic embryogenesis process in leaf tissues is
      accompanied by an overall increase in the amount of proteins secreted into the
      culture medium. Amongst these, three major protein bands of 38 kDa, 32 kDa and 25
      kDa were found in the conditioned media. These extracellular protein bands
      accumulated in the medium of the embryogenic Cichorium hybrid up to 8-fold
      compared with those in the medium of a nonembryogenic variety. 32 and 25 kDa
      proteins were purified from the medium and their identities were determined as
      already described for 38 kDa beta-1,3-glucanases. To investigate their possible
      function in somatic embryogenesis, peptide sequences, serological relationships
      or biochemical properties revealed that there were at least two acidic chitinases
      of 32 kDa and one glycosylated osmotin-like protein of 25 kDa in the embryogenic
      culture medium. Comparing the amounts of the 38 kDa glucanases, the 32 kDa
      chitinases, and the 25 kDa osmotin-like protein present in the conditioned media
      of the embryogenic '474' hybrid and of a non-embryogenic variety, a 2-8-fold
      higher accumulation of these proteins was observed in the embryogenic hybrid
      culture medium. This may suggest that part of the accumulation of these three
      pathogenesis-related (PR) proteins could be correlated with the somatic
      embryogenesis process. Their possible involvement in this developmental process
      is discussed.

PMID- 10937695
TI  - The barley scutellar peptide transporter: biochemical characterization and
      localization to the plasma membrane.
AB  - Thiol-affinity labelling was used to identify and characterize components of the
      peptide transport system in the barley (Hordeum vulgare) scutellar epithelium.
      SDS-PAGE and 2D-PAGE in conjunction with fluorography were used to study
      derivatized proteins. Membrane proteins of 42 kDa and 66 kDa were identified
      using a strategy devised to label substrate protectable protein with the thiol
      specific reagent [14C] N-ethylmaleimide (NEM). The scutellar plasma membrane is
      the anticipated site of transporters involved in the mobilization of endosperm
      storage reserves in the germinating barley grain. The subcellular localization of
      these proteins to the plasma membrane was demonstrated by thiol-affinity
      labelling of high purity plasma membrane vesicles isolated from barley scutellar
      tissue. A peptide transporter, HvPTR1, specific to the barley scutellum has
      recently been cloned in this laboratory. A 66 kDa protein, comparable to the
      predicted molecular mass of HvPTR1, was identified by [14C]NEM labelling studies
      of Xenopus laevis oocytes expressing HvPTR1 cRNA, but not water injected
      controls. Peptide antiserum raised to HvPTR1 also cross-reacted with a 66 kDa
      membrane protein in barley scutellar tissue. This confirms that the 66 kDa
      protein identified here by thiol-affinity labelling studies is the barley
      scutellum peptide transporter HvPTR1, and demonstrates that this protein is
      localized to the plasma membrane of scutellar epithelial cells during
      germination.

PMID- 10937696
TI  - Differential expression of the Arabidopsis genes coding for Em-like proteins.
AB  - Late embryogenesis abundant (lea) genes are a large and diverse group of genes
      highly expressed during late stages of seed development. Five major groups of LEA
      proteins have been described. Two Em genes (group I lea genes) are present in the
      genome of Arabidopsis thaliana L., AtEm1 and AtEm6. Both genes encode for very
      similar proteins which differ basically in the number of repetitions of a highly
      hydrophilic amino acid motif. The spatial patterns of expression of the two
      Arabidopsis Em genes have been studied using in situ hybridization and transgenic
      plants transformed with the promoters of the genes fused to the beta
      glucuronidase reporter gene (uidA). In the embryo, AtEm1 is preferentially
      expressed in the pro-vascular tissues and in meristems. In contrast, AtEm6 is
      expressed throughout the embryo. The activity of both promoters disappears
      rapidly after germination, but is ABA-inducible in roots of young seedlings,
      although in different cells: the AtEm1 promoter is active in the internal tissues
      (vasculature and pericycle) whereas the AtEm6 promoter is active in the external
      tissues (cortex, epidermis and root hairs). The AtEm1 promoter, but not AtEm6, is
      also active in mature pollen grains and collapsed nectaries of young siliques.
      These data indicate that the two Em proteins could carry out at least slightly
      different functions and that the expression of AtEm1 and AtEm6 is controlled at,
      at least, three different levels: temporal, spatial and hormonal (ABA).

PMID- 10937697
TI  - Protein modification by Amadori and Maillard reactions during seed storage: roles
      of sugar hydrolysis and lipid peroxidation.
AB  - The non-enzymatic modifications of proteins through Amadori and Maillard
      reactions play an important role in the loss of seed viability during storage. In
      the present study, the contribution of sugar hydrolysis and lipid peroxidation to
      Amadori and Maillard reactions, and to seed deterioration was investigated in
      mung-bean (Vigna radiata Wilczek). The contents of glucose and lipid peroxidation
      products in seed axes increased significantly during storage. The accumulation of
      Amadori products in seed axes was correlated to the lipid peroxidation, whereas
      the accumulation of Maillard products was closely correlated to sugar hydrolysis.
      The rate of accumulation of Maillard products was not well correlated to the
      content of Amadori products in both seed axes and protein/glucose model system,
      reflecting the complex nature of Amadori and Maillard reactions. The content of
      Amadori products in seed axes increased during the early stages of seed ageing,
      whereas the content of Maillard products increased steadily during the entire
      period of storage. The accumulation of Maillard products in seed axes was
      associated with the decline of seed vigour. These data suggest that, during seed
      ageing, sugar hydrolysis and lipid peroxidation are coupled with non-enzymatic
      protein modification through Amadori and Maillard reactions.

PMID- 10937698
TI  - Analysis of bruchid resistance in the wild common bean accession G02771: no
      evidence for insecticidal activity of arcelin 5.
AB  - Arcelins are abundant seed storage proteins thought to be implicated in the
      resistance of wild Phaseolus vulgaris (L.) genotypes against Zabrotes
      subfasciatus (Boheman), an important storage insect pest of common bean. Here,
      the insecticidal activity of the arcelin-5 variant that is present in the highly
      resistant P. vulgaris accession G02771 was investigated. No correlation could be
      established between the presence of arcelin 5 and the insecticidal effects
      observed in G02771 seeds. Insect feeding assays with artificial seeds into which
      purified arcelin-5 protein was incorporated and with transgenic P. acutifolius
      (A. Gray) seeds in which the arcelin-5 genes were expressed, showed that the
      presence of arcelin-5 proteins, even at elevated levels, was not sufficient to
      achieve adequate resistance against Z. subfasciatus. The same might apply to
      other arcelin variants. Nevertheless, as resistance is clearly closely linked to
      the presence of the arcelin-1 or arcelin-5 locus, arcelins remain useful markers
      in breeding programmes aimed at introgressing high levels of resistance to Z.
      subfasciatus in P. vulgaris cultivars.

PMID- 10937699
TI  - Efficient intergeneric fusion of pea (Pisum sativum L.) and grass pea (Lathyrus
      sativus L.) protoplasts.
AB  - Large numbers of viable protoplasts of pea (Pisum sativum) and grass pea
      (Lathyrus sativus) were efficiently and reproducibly obtained and, for the first
      time, fused. Different procedures for fusion were compared, based either on
      electrofusion (750, 1000, 1250 or 1500 V cm(-1)), or on the use of macro or
      micromethods with a polyethylene glycol (PEG 6000 or PEG 1540), or a glycine/high
      pH solution. Over 10% of viable heterokaryons were obtained, with PEG as the most
      efficient and reproducible agent for protoplast fusion (>20% of viable
      heterokaryons). Both the division of heterokaryons and the formation of small
      calluses were observed.

PMID- 10937700
TI  - Ion-specific mechanisms of osmoregulation in bean mesophyll cells.
AB  - Transient kinetics of net H+, K+, Ca2+, and Cl- fluxes were measured non
      invasively, using an ion-selective microelectrode technique, for bean (Vicia faba
      L.) leaf mesophyll in response to 150 mM mannitol treatment. In a parallel set of
      experiments, changes in the plasma membrane potential and the total proline
      content in leaves were monitored. Regardless of the ionic composition of the bath
      solution, hyperosmotic stress caused a significant increase in the K+ and Cl-
      uptake into mesophyll cells. At the same time, no significant proline changes
      were observed for at least 16 h after the onset of stress. Experiments with
      inhibitors suggested that potassium inward rectifier (KIR) channels, exhibiting
      mechanosensitive properties and acting as primary receptors of osmotic stress,
      are likely to be involved. Due to the coupling by membrane potential, changes in
      K+ and Cl- transport may modify activity of the plasma membrane H+-pump. Such
      coupling may also be responsible for the mannitol-induced oscillations (period of
      about 4 min) in net ion fluxes observed in 90% of plants. Calculations show that
      influx of K+ and Cl- observed in response to hyperosmotic treatment may provide
      an adequate osmotic adjustment in bean mesophyll, which suggests that the
      activity of the plasma membrane transporters for these ions should be targeted to
      improve osmotolerance, at least in this crop.

PMID- 10937701
TI  - Temperature effects on hydraulic conductance and water relations of Quercus robur
      L.
AB  - The effects of temperature on root and shoot hydraulic conductances (g(shoot) and
      g(root)) were investigated for Quercus robur L. saplings. In a first experiment,
      conductances were measured with a High Pressure Flow Meter on excised shoots and
      detopped root systems. The g(root) and g(shoot) increased considerably with
      temperature from 0-50 degrees C. Between 15 degrees C and 35 degrees C, g(shoot)
      and g(root) varied with water viscosity. In a second experiment, the impact of
      temperature-induced changes in g(root) on sapling transpiration (E) and leaf
      water potential (psileaf) was assessed. Intact plants were placed in a growth
      cabinet with constant air and variable soil temperatures. E increased linearly
      with soil temperature but psileaf remained constant. As a consequence, a linear
      relationship was found between E and g(plant). The results illustrate the
      significance of g(plant) for the stomatal control of transpiration and the
      significance of temperature for tree water transport.

PMID- 10937702
TI  - The role of fructan in flowering of Campanula rapunculoides.
AB  - Inulin type fructan was detected in all vegetative organs of Campanula
      rapunculoides L. plants. All flower parts contained fructan at some developmental
      stage. A steady decrease was found in sepals during development. Petals, however,
      stored fructan in the bud stage. A rapid breakdown during opening of the flower
      resulted in high concentrations of glucose and especially fructose that may
      contribute to the osmotic driving force involved in petal expansion. Before
      complete shrivelling, the hexoses were apparently exported from flower parts.
      Fructans were hydrolysed and exported from the stamen and style tissue upon
      flower opening. Similarly, the major fructan reserves in the ovary were broken
      down almost simultaneously with those in other flower parts. Hexoses did not
      reach high levels in the ovary, probably because they were rapidly metabolized
      and/or incorporated by developing seeds.

PMID- 10937703
TI  - Early physiological and cytological events induced by wounding in potato tuber.
AB  - The response of potato tuber (Solanum tuberosum L. cv. Kennebec) to mechanical
      wounding was investigated at different times. Changes in the levels of indole-3
      acetic acid (IAA), polyunsaturated fatty acids (PUFAs) and lipid hydroperoxides
      (LOOHs) were monitored up to 120 min after wounding and related to the
      cytological events occurring up to 24 h. Twenty minutes after injury, an increase
      in IAA and LOOH levels and a decrease in the levels of PUFAs was observed.
      Wounding induced mitoses in differentiated (parenchyma) cells starting at 120
      min, and promoted an increase of mitotic activity in the meristematic cells
      (procambium and bud dome), after 360 min. The inhibition of the increase in LOOHs
      and IAA by lipoxygenase (LOX) inhibitors, as well as the ability of in vitro
      peroxidated linoleic acid to enhance IAA production, suggest a close relationship
      among lipoperoxidation, IAA and mitotic activity in the response of potato tuber
      cells to injury, resulting in a specific growth response, i.e. bud growth and
      periderm formation.

PMID- 10937704
TI  - Developmental changes and water status in tulip bulbs during storage:
      visualization by NMR imaging.
AB  - Magnetic Resonance Imaging (MRI) and light and scanning electron microscopy (SEM)
      were used to follow time-dependent morphological changes and changes in water
      status of tulip bulbs (Tulipa gesneriana L., cv. 'Apeldoorn') during bulb storage
      for 12 weeks at 20 degrees C (non-chilled) or 4 degrees C (chilled) and after
      planting. MR images reflecting the water content, the relaxation times T1 and T2
      (or their reciprocal values, the relaxation rates R1 and R2), and the apparent
      self-diffusion coefficient of water molecules (ADC), were obtained for intact
      bulbs. After planting, scape elongation and flowering occurred only in chilled
      bulbs, while elongation in non-chilled bulbs was retarded. Microscopic
      observations showed different structural components and high heterogeneity of the
      bulb tissues. MRI revealed the elongation of the flower bud during storage, which
      was significantly faster in the chilled bulbs. In addition, MRI demonstrated a
      redistribution of water between different bulb organs, as well as significant
      differences in the pattern of this redistribution between the chilled and non
      chilled bulbs. Generally, R2 relaxation rates became faster in all bulb organs
      during storage. At the same time, ADC values remained constant in the chilled
      bulbs, while exhibiting a significant increase in the non-chilled bulbs.

PMID- 10937705
TI  - Evidence that P deficiency induces N feedback regulation of symbiotic N2 fixation
      in white clover (Trifolium repens L.).
AB  - Trifolium repens L. was grown to test the following hypotheses: when P is
      deficient (i) N2 fixation decreases as a result of the plant's adaptation to the
      low N demand, regulated by an N feedback mechanism, and (ii) the decrease in the
      photosynthetic capacity of the leaves does not limit N2 fixation. Severe P
      deficiency prevented nodulation or stopped nodule growth when the P deficiency
      occurred after the plants had formed nodules. At low P, the proportion of whole
      plant-N derived from symbiotic N2 fixation decreased, whereas specific N2
      fixation increased and compensated partially for poor nodulation. Leaf
      photosynthesis was reduced under P deficiency due to low Vc,max and Jmax. Poor
      growth or poor performance of the nodules was not due to C limitation, because
      (i) the improved photosynthetic performance at elevated pCO2 had no effect on the
      growth and functioning of the nodules, (ii) starch accumulated in the leaves,
      particularly under elevated pCO2, and (iii) the concentration of WSC in the
      nodules was highest under P deficiency. Under severe P deficiency, the
      concentrations of whole-plant-N and leaf-N were the highest, indicating that the
      assimilation of N exceeded the amount of N required by the plant for growth. This
      was clearly demonstrated by a strong increase in asparagine concentrations in the
      roots and nodules under low P supply. This indicates that nodulation and the
      proportion of N derived from symbiotic N2 fixation are down-regulated by an N
      feedback mechanism.

PMID- 10937706
TI  - Expression of thioredoxins f and m, and of their targets fructose-1,6
      bisphosphatase and NADP-malate dehydrogenase, in pea plants grown under normal
      and light/temperature stress conditions.
AB  - Thioredoxins (Trxs) f and m, as well as their targets chloroplast fructose-1,6
      bisphosphatase (FBPase) and NADP+-malate dehydrogenase (NADP-MDH), displayed
      transcriptional expression in both photosynthetic and non-photosynthetic organs
      of pea plants (Pisum sativum L. cv. Lincoln) grown for 50 d under normal
      irradiance. However, whereas Trx m and both target enzymes were poorly expressed
      in non-photosynthetic tissues, the content of the precursor form of the Trx f
      specific mRNA was high in pea roots. In contrast, the translational expression of
      Trx f was low in this organ. The high FBPase activity in immature seeds, and the
      low activity of leaves, must be related to high starch synthesis in the first,
      and with high sucrose formation in the second. The transcriptional expression of
      FBPase and NADP+-MDH, and to a lesser extent that of Trxs f and m, was inhibited
      under low irradiance in plants grown under both normal and high temperatures. Pea
      plants grown at low temperature displayed a high level of mRNAs for Trxs and
      their targets, especially when the growth was carried out at low light. To a
      lesser extent, similar behaviour was observed at the protein level. Chloroplasts
      of mesophyll leaf cells of pea plants grown under saturating light, or under sub
      saturating continuous irradiance, showed broken envelopes, distorted structural
      elements and disorganized starch grains, as a consequence of a photobleaching
      process and high starch accumulation.

PMID- 10937707
TI  - Effects of drought on photosynthesis in Mediterranean plants grown under enhanced
      UV-B radiation.
AB  - The effects of drought on the photosynthetic characteristics of three
      Mediterranean plants (olive, Olea europea L.; rosemary, Rosmarinus officinalis
      L.; lavender, Lavandula stoechas L.) exposed to elevated UV-B irradiation in a
      glasshouse were investigated over a period of weeks. Drought conditions were
      imposed on 2-year-old plants by withholding water. During the onset of water
      stress, analyses of the response of net carbon assimilation of leaves to their
      intercellular CO2 concentration were used to examine the potential limitations
      imposed by stomata, carboxylation velocity and capacity for regeneration of
      ribulose 1,5-bisphosphate on photosynthesis. Measurements of chlorophyll
      fluorescence were used to determine changes in the efficiency of light
      utilization for electron transport, the occurrence of photoinhibition of
      photosystem II photochemistry and the possibility of stomatal patchiness across
      leaves. The first stages of water stress produced decreases in the light
      saturated rate of CO2 assimilation which were accompanied by decreases in the
      maximum carboxylation velocity and the capacity for regeneration of ribulose 1,5
      bisphosphate in the absence of any significant photodamage to photosystem II.
      Leaves of rosemary and lavender were more sensitive than those of olive during
      the first stages of the drought treatment and also exhibited increases in
      stomatal limitation. With increasing water stress, significant decreases in the
      maximum quantum efficiency of photosystem II photochemistry occurred in lavender
      and rosemary, and stomatal limitation was increased in olive. No indication of
      any heterogeneity of photosynthesis was found in any leaves. Drought treatment
      significantly decreased leaf area in all species, an important factor in drought
      induced decreases in photosynthetic productivity. Exposure of plants to elevated
      UV-B radiation (0.47 W m(-2)) prior to and during the drought treatment had no
      significant effects on the growth or photosynthetic activities of the plants.
      Consequently, it is predicted that increasing UV-B due to future stratospheric
      ozone depletion is unlikely to have any significant impact on the photosynthetic
      productivity of olive, lavender and rosemary in the field.

PMID- 10937708
TI  - Anther dehiscence in two-rowed barley (Hordeum distichum) triggered by mechanical
      stimulation.
AB  - Pricking or pressing an ovary can induce anther dehiscence in cleistogamous two
      rowed barley in the absence of lodicule swelling. This response is considered to
      be inherited from a chasmogamous ancestor in which anther dehiscence is induced
      by the stimulus given to the pistil by the lodicule swelling, which causes floret
      opening.

PMID- 10937709
TI  - Phenylacetamides as selective alpha-1A adrenergic receptor antagonists.
AB  - A novel class of potent and selective alpha-1a receptor antagonists has been
      identified. The structures of these antagonists were derived from truncating the
      4-aryl dihydropyridine subunit present in known alpha-1a antagonists. The design
      principles which led to the discovery of substituted phenylacetamides, the
      synthesis and SAR of key analogues, and the results of select in vitro and in
      vivo studies are described.

PMID- 10937710
TI  - Selective alpha1a adrenergic receptor antagonists based on 4-aryl-3,4
      dihydropyridine-2-ones.
AB  - A series of alpha1a receptor antagonists derived from a 4-aryl-3,4
      dihydropyridine-2-one heterocycle is disclosed. Potency in the low nanomolar to
      picomolar range along with high selectivity was obtained. In vivo efficacy in a
      prostate contraction model in rats was observed with a few derivatives.

PMID- 10937711
TI  - Synthesis and antimicrobial activity of some isoindolin-1-ones derivatives.
AB  - A range of N-substituted isoindolin-1-ones was prepared and their potential as
      novel antimicrobial agents was investigated. MIC values for active compounds were
      determined and reported.

PMID- 10937712
TI  - Template-directed interference footprinting for RNA based on inosine-specific
      cleavage.
AB  - We report here the development of a Template-directed Interference (TDI)
      footprinting assay for RNA. The TDI nucleotide analogue inosine (I) lacks the
      exocyclic amine of G and is a suitable probe for the role of this group in RNA
      structure and function. Using an I-specific cleavage protocol we identified three
      functionally significant G residues in the Tetrahymena ribozyme. These residues
      are proximal to the active site of the folded intron and likely contribute to the
      positioning of substrates at the catalytic core.

PMID- 10937713
TI  - Solid-phase synthesis of an arylsulfone hydroxamate library.
AB  - Synthesis of an arylsulfone hydroxamate lead optimization library is presented.
      Biological activity of representative examples is given to demonstrate the value
      of this approach for lead optimization.

PMID- 10937714
TI  - N-acylated alpha-(3-pyridylmethyl)-beta-aminotetralin antagoinists of the human
      neuropeptide Y Y5 receptor.
AB  - Alpha-(3-Pyridylmethyl)-beta-aminotetralins were acylated with amino-piperidinyl
      and-pyrrolidinyl acetic acids, and with (aminomethyl)cyclohexanecarboxylic acid.
      Reaction with acyl chlorides, chloroformates, and isocyanates gave amides 8e,
      carbamates 9, and ureas 10, which bound to the Y5 receptor with nanomolar
      affinity. Congeners 11a and 11d containing a terminal benzimidazolone group were
      shown to be functional Y5 antagonists.

PMID- 10937715
TI  - Novel inhibitors of AP-1 and NF-kappaB mediated gene expression: structure
      activity relationship studies of ethyl 4-[(3-methyl-2,5-dioxo(3
      pyrrolinyl))amino]-2-(trifluoromethyl)++ +pyrimidi ne-5-carboxylate.
AB  - In an effort to identify novel inhibitors of AP-1 and NF-kappaB mediated
      transcriptional activation, several analogues of ethyl 4-[(3-methyl-2,5-dioxo(3
      pyrrolinyl))amino]-2-(trifluoromethyl)pyr imidine-5-carboxylate (1) were
      synthesized and tested in two in vitro assays. The 2-(2'-thienyl) substituted
      compound (11) was identified as the most potent in this series.

PMID- 10937716
TI  - Salicylamide inhibitors of influenza virus fusion.
AB  - Structural variation of the quinolizidine heterocycle of the influenza fusion
      inhibitor BMY-27709 was examined by several topological dissections in order to
      illuminate the critical features of the ring system. This exercise resulted in
      the identification of a series of synthetically more accessible
      decahydroquinolines that retained the structural elements of BMY-27709 important
      for antiviral activity. The 2-methyl-cis-decahydroquinoline 6f was the most
      potent influenza inhibitor identified that demonstrated an EC50 of 90 ng/mL in a
      plaque reduction assay.

PMID- 10937717
TI  - Phenyl sulfur mustard derivatives of distamycin A.
AB  - The design, synthesis, and cytotoxic activity of novel benzoyl and cinnamoyl
      sulfur mustard derivatives of distamycin A are described and structure activity
      relationships are discussed. These sulfur mustards are more potent cytotoxics
      than corresponding nitrogen mustards in spite of the lower alkylating power,
      while their sulfoxide analogues are substantially inactive. Cinnamoyl sulfur
      mustard derivative (7) proved to be one of the most active distamycin-derived
      cytotoxics, about 1000 times more potent than melphalan.

PMID- 10937718
TI  - Synthesis of novel ferrocenyl sugars and their antimalarial activities.
AB  - The synthesis of twelve types of novel ferrocenyl sugars and their biological
      properties towards the malaria parasite (P. falciparum) and mouse cancer cell
      (FM3A) are described.

PMID- 10937719
TI  - Synthesis and biological activity of phenoxyphenyl oxamic acid derivatives
      related to L-thyronine.
AB  - The synthesis of substituted phenoxyphenyl oxamic acid derivatives related to L
      thyronine (L-T3) is described. The in vitro and in vivo cholesterol lowering and
      cardiovascular effects of these compounds are presented and discussed.

PMID- 10937720
TI  - Combined tachykinin receptor antagonist: synthesis and stereochemical structure
      activity relationships of novel morpholine analogues.
AB  - We report herein the synthesis and stereochemical structure-activity
      relationships of novel morpholine analogues 12 and 13 with regards to NK1, NK2
      and NK3 tachykinin receptor binding affinity. An essential requirement for more
      potent binding affinities was controlled by absolute configuration. (S,R)-12 and
      (S,R)-13 exhibited high binding affinities for NK1, NK2 and NK3 receptors.

PMID- 10937721
TI  - Inhibition of dopamine receptors by endogenous amines: binding to striatal
      receptors and pharmacological effects on locomotor activity.
AB  - Endogenous amine 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) derivatives are
      synthesized. and their activity for dopaminergic systems are evaluated in vitro
      and in vivo by receptor binding assay and pharmacological tests. It is proposed
      that 1BnTIQ derivatives can act as endogenous dopaminergic antagonists.

PMID- 10937722
TI  - Antitumor promoting activities of 3-O-acyl-(-)epigallocatechins.
AB  - As an exploratory investigation of antitumor promoting compounds, 3-O-acyl-(-)
      epigallocatechins possessing a straight-, branched-, phenyl-inserted- or 1,4
      phenylene-inserted-acyl chain of varying length from C4 to C18 were synthesized
      and evaluated their inhibitory effects against the activation of the Epstein-Barr
      virus early antigen (EBV-EA). It was indicated that the epigallocatechin
      derivatives having the straight- or branched-acyl chain of C8 to C11 carbon atoms
      achieve marked effects.

PMID- 10937723
TI  - Efficient synthesis of 8-oxo-dGTP: a mutagenic nucleotide.
AB  - An efficient synthesis of mutagenic and oxidative DNA damage product, 8-oxo-dGTP
      (4) has been achieved in high yield, along with a serendipitous generation of 8
      dimsyl-dG (2). In combination with dPTP (5), 8-oxo-dGTP (4) can be formulated
      into a kit for investigating DNA random mutagenesis.

PMID- 10937724
TI  - Synthesis and biological evaluation of 1-azabicyclo-[3.2.1]octanes: new dopamine
      transporter inhibitors.
AB  - The synthesis and biological activity of a series of 6-substituted 1
      azabicyclo[3.2.1]octanes are described. 1-Azabicyclo[3.2.1]octanes represent a
      new class of compounds that exhibit monoamine transporter inhibitory activity
      highly dependent on the overall topology and the absolute stereochemistry of the
      molecule.

PMID- 10937725
TI  - Anhydride modified cantharidin analogues: synthesis, inhibition of protein
      phosphatases 1 and 2A and anticancer activity.
AB  - Two series of anhydride modified cantharidin analogues were synthesised and
      screened for their phosphatase inhibition (PP1 and PP2A) and cytotoxicity in
      various cancer cell lines (Ovarian A2780, ADDP; Osteosarcoma 143B; and Colon
      HCT116 and HT29). One series was synthesised by a novel, high yielding one-pot
      hydrogenation-ring-opening-esterification procedure, the other by acid catalysed
      acetal formation. Analogues 5-7 and 9 displayed moderate PP2A selectivity (ca. 5-
      to 20-fold) and inhibition typically in the low microM range (comparable, in some
      cases to cantharidin). The anticancer activity of these analogues varied with the
      cell line under study; however, many of them showed selective cytotoxicity for
      the colon tumour cell lines.

PMID- 10937726
TI  - Production and application of LPA polyclonal antibody.
AB  - By using colloidal gold as a hapten carrier, a kind of antibody against
      lysophosphatidic acid (LPA) was developed and used to successfully detect 500
      ng/mL LPA in dot immunogold filtration assay. Such application of the LPA
      antibody could offer us a way to diagnose ovarian cancer at its early stage.

PMID- 10937728
TI  - One-pot synthesis and biological evaluation of aspergillamides and analogues.
AB  - A one-pot total synthesis of aspergillamide and analogues by a solution phase Ugi
      multi component reaction (MCR) is described. The reaction is easily performed in
      96-well plates and offers a facile access to diverse aspergillamide analogue
      compound libraries. The antibiotic and cytotoxic activity of these compounds is
      measured. Several of them are more potent than the natural product.

PMID- 10937727
TI  - Improved antibacterial activities of coumarin antibiotics bearing 5',5'
      dialkylnoviose: biological activity of RU79115.
AB  - A new series of coumarin inhibitors of DNA gyrase B bearing a N
      propargyloxycarbamate at C-3' of various 5',5'-dialkylnoviose, including RU79115,
      were synthesised and their antibacterial activities have been delineated.
      Introduction of dialkyl substituents at 5'5'-position of noviose leads to
      coumarin analogues with improved in vitro and in vivo antibacterial activity.

PMID- 10937729
TI  - 5-Alkyltryptamine derivatives as highly selective and potent 5-HT1D receptor
      agonists.
AB  - A series of 5-alkyltryptamines (6) and the corresponding conformationally
      constrained analogues (8) have been synthesized. The structure activity
      relationships (SAR) at the 5-position of the indole skeleton and the ethylamine
      side chain have been studied. Functional activities were assessed using isolated
      rabbit saphenous vein. Potent, selective ligands were found (6e, Ki 2.5 nM, 5
      HT1B/5-HT1D 125-fold) that have potential for treating acute migraine.

PMID- 10937730
TI  - Preparation of L-alpha-phosphatidyl-D-myo-inositol 3-phosphate (3-PIP) and 3,5
      bisphosphate (3,5-PIP2).
AB  - Practical, asymmetric total syntheses of the title phospholipids from a readily
      available myo-inositol derivative as well as short chain and cross-linkable
      aminoether analogues are described.

PMID- 10937731
TI  - Parallel solid-phase synthesis of vitronectin receptor (alphavbeta3) inhibitors.
AB  - A combinatorial approach for rapid optimization of a vitronectin receptor
      (alphavbeta3) inhibitor lead was accomplished by solid-phase synthesis.
      Orthogonally bis protected 2,3-diaminopropionic acid was used to immobilize the C
      terminus of the molecule. Selective deprotection and functionalization of the
      alpha-amino group followed by acyl resorcinol scaffold attachment and N-terminus
      diversification was used to explore structure activity relationship (SAR).

PMID- 10937733
TI  - Quinolones as gonadotropin releasing hormone (GnRH) antagonists: simultaneous
      optimization of the C(3)-aryl and C(6)-substituents.
AB  - A series of 3-arylquinolones was prepared and evaluated for their ability to act
      as gonadotropin releasing hormone (GnRH) antagonists. A variety of substitution
      patterns of the 3-aryl substituent are described. The 3,4,5-trimethylphenyl
      substituent (23h) was found to be optimal.

PMID- 10937732
TI  - 6-Bicyclopiperazinyl-1-arylsulfonylindoles and 6-bicyclopiperidinyl-1
      arylsulfonylindoles derivatives as novel, potent, and selective 5-HT6 receptor
      antagonists.
AB  - A novel series of 6-bicyclopiperazinyl-1-arylsulfonylindoles and 6
      bicyclopiperidinyl-1-arylsulfonylindoles derivatives was synthesized and found to
      be potent and selective 5-HT6 receptor antagonists.

PMID- 10937734
TI  - Synthesis and evaluation of quinoxalinones as HIV-1 reverse transcriptase
      inhibitors.
AB  - A series of 3,3-disubstituted quinoxalinones was prepared and evaluated as HIV-1
      reverse transcriptase inhibitors. The N-allyl (6b and 6f), N-cyclopropylmethyl
      (6a, 6g, 6h, and 6k) and N-carboalkoxy (6m-6y) substituted compounds displayed
      activity comparable or better than Efavirenz and GW420867X.

PMID- 10937735
TI  - Polymethylcarborane as a novel bioactive moiety: derivatives with potent retinoid
      antagonistic activity.
AB  - 4[(Deca-B-methyl-1,12-dicarba-closo-dodecaboran-1-yl)c arbamoyl]benzoic acid and
      its congeners showed potent antagonistic activity at concentrations of 10(-7)-10(
      8) M on the differentiation-inducing action of retinoids towards human
      promyelocytic leukemia HL-60 cells. This is the first example of derivatives of
      polymethylcarborane, which resembles C60 in size, with biological activity.

PMID- 10937737
TI  - Synthesis and evaluation of aza HUN-7293.
AB  - The aza analogue of the cyclic heptadepsipeptide HUN-7293 (1), which is a potent
      naturally occurring inhibitor of inducible cell adhesion molecule expression, and
      its C2(3) (MLEU3 C2) epimer were prepared via solution-phase synthesis.
      Biological evaluations of these two compounds as inhibitors of cell adhesion
      molecules expression are detailed.

PMID- 10937736
TI  - Nonbenzamidine compounds as selective factor Xa inhibitors.
AB  - Nonbenzamidine compounds (imidazole, pyridine, pyrimidine, and thiazole
      derivatives) as selective serine protease factor Xa inhibitors are discussed.

PMID- 10937738
TI  - Synthesis and biological evaluation of 1,3,4-triaryl-3-pyrrolin-2-ones, a new
      class of selective cyclooxygenase-2 inhibitors.
AB  - The synthesis and structure activity relationships (SAR) of a series of novel
      selective COX-2 inhibitors are reported. The results show that some of the 1,3,4
      triaryl-3-pyrrolin-2-ones 1 are more potent as COX-2 inhibitors than celecoxib,
      and that lactam Id has the same selectivity.

PMID- 10937739
TI  - Synthesis of aminophosphonate haptens for an aminoacylation reaction between
      methyl glucoside and a beta-alanyl ester.
AB  - Two 2-aminophosphonate haptens derived from methyl alpha-D-glucopyranoside were
      synthesized to mimic the transition-state of a transesterification reaction
      between methyl alpha-D-glucopyranoside and 4-nitrophenylester of tert-BOC-beta
      alanine. Two sets of monoclonal antibodies were generated against these haptens.

PMID- 10937740
TI  - Studies on the novel anti-staphyloccal compound nematophin.
AB  - A number of analogues of the recently described compound nematophin were prepared
      and studied for antibacterial activity. The 2-phenyl derivative was found to
      exhibit exceptional activity against methicillin resistant Staphylococcus aureus
      (MRSA) whereas the isosteric benzimidazole analogue was much less active.

PMID- 10937741
TI  - Diels-Alder approach to tetralin-based constrained alpha-amino acid derivatives.
AB  - Tetralin-based constrained alpha-amino acid derivatives were prepared via [4 + 2]
      cycloaddition reaction as a key step. Here sultine is used as a latent diene and
      2-acetamidoacrylate serves as a dienophile component.

PMID- 10937742
TI  - A simple polar deacetylated caloporoside derivative is a positive modulator of
      the GABA(A) chloride channel complex in cortical mammalian neurones.
AB  - Synthesis of octyl-O-beta-D-mannopyranoside, a caloporoside analogue was achieved
      by the activation of 2,3,4,6-rerra-O-benzyl-1-O-1',3'2'-dioxaphosphacyclohexane-a
      lpha,beta-D-mannopyranosyl-2-oxide with TMSOTf (Trimethyl silyl triflate) and
      subsequent debenzylation. At 100 microM the molecule significantly and reversibly
      increased the magnitude of GABA(A) currents evoked in cultured rat pyramidal
      neurones whilst concomitantly reducing the incidence of spontaneous synaptic
      activity. These results contradict earlier proposals that such molecules bind to
      the TBPS (tert-Butylbicyclophosphorothionate) site to block the chloride channel.

PMID- 10937743
TI  - Grignard-mediated synthesis and preliminary biological evaluation of novel 3
      substituted farnesyl diphosphate analogues.
AB  - A series of substituents was installed at the 3 position of farnesyl diphosphate
      through a copper-cyanide mediated coupling of a vinyl triflate with various
      Grignard reagents. These novel FPP mimetics were then evaluated as inhibitors of
      or substrates for mammalian protein farnesyl transferase. The IC50 values for
      these compounds range from 18 to 10,100 nm, with the 3-isopropenyl analogue being
      one of the most potent FPP-mimetic mFTase inhibitors yet synthesized.

PMID- 10937744
TI  - Synthesis of two new heteroaromatic beta-carboline-fused pentacycles. Observation
      of a new intercalating agent.
AB  - Five-step synthetic routes of two new polyfused heterocycles: indazolo[3,2-a]
      beta-carboline (3) and benzo[4',5'][1,2,3]triazino[6,1-a]-beta-carbolinium salt
      (10) applying Pd(0)-catalyzed cross-coupling reaction have been elaborated.

PMID- 10937745
TI  - Development of peptidyl alpha-keto-beta-aldehydes as new inhibitors of cathepsin
      L--comparisons of potency and selectivity profiles with cathepsin B.
AB  - We have utilized previously known substrate and inhibitor specificity profiles
      for the lysosomal cysteine protease, cathepsin L, to design a new series of
      putative inhibitors of this enzyme, based on di- and tri-peptidyl alpha-keto-beta
      aldehydes. Kinetic evaluation of these compounds revealed Z-Phe-Tyr(OBut)-COCHO,
      with a Ki 0.6 nM, to be the most potent, synthetic reversible inhibitor of
      cathepsin L reported to date.

PMID- 10937746
TI  - Metalloporphyrin catalyzed oxidation of N-hydroxyguanidines: a biomimetic model
      for the H2O2-dependent activity of nitric oxide synthase.
AB  - A chemical model for the H2O2 promoted oxidation by nitric oxide synthase (NOS)
      has been developed. Biomimetic oxidations were carried out using H2O2 and
      tetrakis(perfluorophenyl)porphyrinato-iron(III) chloride (FeTPPF20) as a
      catalyst. Similarly to NOS our model system produces Ndelta-cyanoornithine,
      citrulline and NO from NOHA and did not oxidize arginine itself. Based on these
      results we propose a peroxide shunt to be involved in the catalytic cycle of NOS.
      To the best of our knowledge this is the first chemical system that
      semiquantitatively mimics NOS activity.

PMID- 10937747
TI  - Radiological changes of the symphysis in ankylosing spondylitis.
AB  - PURPOSE: To evaluate the symphyseal changes in patients with ankylosing
      spondylitis. MATERIAL AND METHODS: Radiological-morphological changes of the
      symphysis were studied in 68 patients (66 men, 2 women) with ankylosing
      spondylitis whose age ranged from 21 to 75 years. The duration of the disease was
      from 2 to 50 years. RESULTS AND CONCLUSION: Changes in the symphysis were found
      in 16 patients (23.5%) and were less prominent than findings in the sacroiliac
      joints. We classified these changes into four stages: minimal changes, apparent
      destruction, reparation and ankylosis. The third and the fourth stages of the
      changes in the symphsis were found more frequently in patients who suffered from
      the disease for more than 15 years. Radiological evaluation of symphyseal changes
      can be helpful in the evaluation of disease progression as well as in
      establishing a differential diagnosis.

PMID- 10937749
TI  - The pelvic digit--a rare developmental anomaly. A case report with CT correlation
      and review of the literature.
AB  - Radiography of the pelvis may incidentally reveal a rare congenital anomaly
      called "pelvic digit" and it is important to be aware of its existence in order
      to differentiate it from acquired abnormalities due to trauma. A case of a pelvic
      digit with CT correlation is presented and the literature is reviewed.

PMID- 10937748
TI  - Radiation dose and image information in computed radiography. A phantom study of
      angle measurements in the weight-bearing knee.
AB  - PURPOSE: To establish a correlation between radiation dose and diagnostic
      accuracy when employing a new digital method for angle determinations. The
      specific intention was to determine how far the radiation dose can be reduced
      without losing measuring accuracy and to compare this radiation dose with that
      employed with our conventional method. MATERIAL AND METHODS: An image succession
      of an anthropomorphic phantom was generated with a computed radiography (CR)
      system, by reducing the exposure stepwise. The images were archived and
      transferred to a workstation for evaluation. The intraobserver variation of two
      angle determinations was used as an indicator of the evaluation accuracy. Patient
      radiation doses were measured with thermoluminescent dosimeters. The energy
      imparted, indicating the relative risk associated with exposure to ionising
      radiation, and the effective dose, which determines the absolute risk, were
      calculated. RESULTS AND CONCLUSION: No significant correlation was found between
      patient dose and measuring accuracy within the evaluated exposure interval. At
      the lowest exposure of the CR system, the energy imparted to the patient was 30
      microJ. Compared with our conventional analogue method this is a reduction by
      98%. The effective dose was as low as 1.5 microSv. The CR technique creates
      possibilities to adapt exposure parameters, and thus the radiation dose to the
      patient, according to the purpose of the investigation.

PMID- 10937750
TI  - Intraosseous lipoma of the frontal bone. A case report.
AB  - Intraosseous lipomas are among the most uncommon bone tumors. They arise most
      often in the appendicular skeleton. There are very few reported cases of
      intraosseous lipomas within the skull bones. We report a case of intraosseous
      lipoma of the frontal bone with conventional radiography and CT findings.

PMID- 10937751
TI  - MR imaging in clinically suspected acute cholecystitis. A comparison with
      ultrasonography.
AB  - PURPOSE: The diagnostic value of fast pulse sequences in MR imaging was compared
      with US in patients with clinically suspected acute cholecystitis. MATERIAL AND
      METHODS: In a prospective study of 94 patients, 35 were examined with both MR and
      US within 24 h. RESULTS: MR diagnoses were acute cholecystitis in 23, gallbladder
      and common bile duct stones in 3, other pathologic conditions of the abdomen in 7
      and normal in 2 patients. US diagnoses were acute cholecystitis in 17,
      gallbladder stones in 8, other pathologic conditions of the abdomen in 2, normal
      in 5 and non-conclusive in 3 patients. CONCLUSION: MR has a higher sensitivity
      than US for diagnosing acute cholecystitis and, with increased accessibility, may
      be the first imaging method.

PMID- 10937752
TI  - Hepatic falciform artery. Angiographic findings in 25 patients.
AB  - PURPOSE: To determine the frequency of hepatic falciform artery (HFA) occurrence
      on celiac or hepatic angiograms and elucidate the anatomy and clinical
      importance. MATERIAL AND METHODS: Among 1,250 patients who underwent celiac or
      hepatic arteriography, we encountered 25 patients (2%) with a HFA. Prospectively,
      CT hepatic falciform arteriography (CTHA) was performed in 4 patients.
      Indigocarmine dye was injected into the HFA in 6 patients to evaluate whether the
      abdominal skin was stained. Embolization of the HFA before chemoembolization for
      hepatocellular carcinoma was performed in 4 patients to prevent abdominal wall
      injury. RESULTS: Among 25 patients, the HFA arose as a terminal branch of the
      middle hepatic artery in 14 patients (56%) and of the left hepatic artery in 11
      patients (44%). The vessel was single in 18 patients (72%) and double in 7
      patients (28%). Two vessels ran side by side along the hepatic falciform
      ligament. On CTHA, the HFA ran within the hepatic falciform ligament and the
      branches were connected with the liver around the hepatic falciform ligament.
      After indigocarmine dye injection, the stain of abdominal skin was recognized in
      all 6 patients. No abdominal wall injury occurred in any of the 4 patients who
      were subjected to hepatic chemoembolization. CONCLUSION: HFA is an extrahepatic
      pathway which runs to the abdominal wall. Before chemoembolization of the middle
      or left hepatic artery for hepatic malignancy, the HFA should be recognized.

PMID- 10937753
TI  - Pancreatoblastoma. Three original cases and review of the literature.
AB  - PURPOSE: To describe the characteristics of pancreatoblastoma. MATERIAL AND
      METHODS: We studied 3 cases of pancretoblastoma and reviewed another 59 cases.
      Parameters analyzed were tumor site, hemorrhage, capsule formation, necrosis,
      vascularity, production of alpha-fetoprotein (AFP), cystic changes and
      calcification. RESULTS: The diagnostic findings were as follows: pancreatic head
      origin (24/54, 44%), pancreatic body and tail origin (30/54, 56%), hemorrhage
      (16/17, 94%), capsule formation (24/26, 92%), necrosis (28/31, 90%),
      hypervascularity (10/14, 71%), production of AFP (19/28, 68%), cystic changes
      (11/16, 69%), and calcification (10/21, 48%). All neonatal cases demonstrated
      cystic changes. Three of them were patients with Beckwith-Wiedmann syndrome. The
      incidence of capsule formation and calcification was not related to the origin of
      the tumor. CONCLUSION: The most common features of pancreatoblastoma are
      hemorrhage, capsule formation and necrosis.

PMID- 10937754
TI  - Percutaneous management of occluded biliary duct endoprostheses.
AB  - PURPOSE: To present interventional methods for percutaneous treatment of patients
      with occluded bile duct endoprostheses. MATERIAL AND METHODS: Thirteen patients
      with endoscopically inserted occluded or damaged bile duct endoprostheses and
      recurrent jaundice were treated percutaneously. Endoscopic treatment was not
      available in 2 cases and unsuccessful in 11 other patients. Eleven interventions
      were performed under systemic sedation and local anaesthesia and 2 under general
      anaesthesia. The endoprostheses were dislodged to the bowel using different
      interventional devices. Adequate bile duct drainage was subsequently achieved by
      insertion of self-expanding metallic stents. RESULTS: All procedures were
      accomplished successfully and without immediate serious complications. Two
      metallic stents and 18 plastic endoprostheses were dislodged to the bowel using
      percutaneous interventional techniques. One plastic endoprosthesis became bent in
      the duodenum and had to be removed endoscopically due to abdominal pain. None of
      the other endoprostheses left in the bowel caused any symptoms. Two patients died
      during the first week after the procedure due to progressive liver failure.
      CONCLUSION: Occluded bile duct endoprostheses can be safely dislodged to the
      bowel and replaced by metallic stents using percutaneous interventional
      techniques.

PMID- 10937755
TI  - Intraductal papillary tumors of the pancreas. Histopathologic correlation of MR
      cholangiopancreatography findings.
AB  - PURPOSE: To evaluate MR cholangiopancreatography (MRCP) findings of intraductal
      papillary tumors of the pancreas and correlate them with histopathology. MATERIAL
      AND METHODS: Seventeen patients with intraductal papillary tumor of the pancreas
      underwent MRCP before surgery. MRCP findings were correlated to histopathology
      with regard to the presence of septa and excrescent nodules in the cystic lesion,
      communication between the cystic lesion and the main pancreatic duct (MPD),
      degree of dilatation of MPD, and dilatation of the common bile duct (CBD).
      RESULTS: MRCP demonstrated septa in 17 cases (100%), excrescent nodules in 8
      cases (47.1%), communication between the intraductal papillary tumor and the MPD
      in 14 cases (82.3%), dilatation of MPD over 50% in 6 cases (35.3%), and
      dilatation of CBD in 3 cases (17.6%). These findings showed excellent correlation
      with histopathology. The septum on MRCP corresponded with a layer of connective
      tissue with pancreatic duct epithelium. Excrescent nodules in the carcinomas
      consisted not only of malignant cells, but also of dysplasia and adenoma.
      Excrescent nodules in adenomas were consistent not only with minimal papillary
      growth of adenoma, but also with proliferation of fibrosis, and hematoma and
      organized fibrin with minimal fibrosis. Pancreatic tissue was affected by chronic
      pancreatitis in all cases. Cases with dilatation of CBD on MRCP were due to
      microscopic invasion by the carcinoma. CONCLUSION: MRCP appearances of
      intraductal papillary tumors are well correlated with the findings at
      histopathology.

PMID- 10937756
TI  - Non-invasive myocardial iron assessment in thalassaemic patients. T2 relaxometry
      and magnetization transfer ratio measurements.
AB  - PURPOSE: To compare T2 relaxometry and magnetization transfer ratio (MTR)
      measurements of myocardial tissue in normal volunteers and thalassaemic patients
      for assessment of the myocardial iron levels. MATERIAL AND METHODS: All
      examinations were done on a 1 T MR system using a multi-echo spin-echo sequence
      with 8 echoes for T2 measurements and a gradient echo sequence for MTR
      measurements. Diastolic cardiac triggering was used in both sequences. Ten
      patients and 10 normal subjects were included in the study. T2 and MTR
      measurements were correlated with serum ferritin levels. RESULTS: Regression
      analysis between T2 and MTR measurements and ferritin demonstrated a reversed
      linear relationship, (r=-0.932, p<0.05) and (r= -0.824, p<0.05), respectively.
      Mean T2 relaxation time and mean MTR of the normal subjects (57.95+/-4.9 ms and
      43.70+/-3.3%) was significantly higher than that of the thalassaemic patients
      (38.8+/-6.2 ms and 26.40+/-6.1%) (p<0.01), respectively. CONCLUSION: MTR
      measurements can be used to complement T2 measurements for non-invasive
      myocardial iron assessment.

PMID- 10937757
TI  - Optimal tube current for lung cancer screening with low-dose spiral CT.
AB  - PURPOSE: To determine the optimal tube current for spiral CT for lung cancer
      screening. MATERIAL AND METHODS: Low-dose spiral CT images from 20 subjects were
      obtained with 50 mA, 25 mA, 10 mA and 5 mA tube currents. The accuracy in
      detecting 21 nodules measuring 3 to 14 mm in diameter was tested using receiver
      operating characteristics (ROC) to determine the diagnostic accuracy and
      statistical significance. RESULTS: Compared with 50 mA, 25 mA showed no
      statistical difference. A significant difference was seen between 50 mA and 5 mA
      images and between 25 mA and 10 mA images, in the detection of lung parenchymal
      nodular lesions. CONCLUSION: Approximately 25 mA is the optimal tube current for
      the detection of pulmonary nodules as it allows a reduction of the radiation dose
      without sacrificing diagnostic accuracy.

PMID- 10937758
TI  - Imaging end-stage kidney disease in adults. Low-field MR imaging with
      magnetization transfer vs. ultrasonography.
AB  - PURPOSE: To 1) assess the potential of magnetization transfer (MT)-weighted MR
      imaging to improve the often poor visibility of native kidneys in patients with a
      renal transplant; and 2) compare low-field MR imaging and ultrasonography (US)
      for imaging these fibrotic kidney remnants. MATERIAL AND METHODS: Seventy-two
      native kidneys of 36 patients were prospectively evaluated with US and MR. In low
      field (0.1 T) MR imaging, T1-, T2- and MT-weighted sequences were used. MT
      weighted images were compared with T2-weighted images in their ability to
      delineate the kidneys from their surroundings whereas US and MR were compared for
      detection of renal cysts and possible solid tumors. RESULTS: MT-weighted images
      proved superior to conventional T2-weighted images in producing contrast between
      the kidney remnants and their fatty surroundings. Although US revealed a few
      small renal cysts that were not seen at MR images, no statistical difference was
      found between the two modalities in this respect. CONCLUSION: MT imaging, due to
      its unique protein-specific signal depression, offers significantly improved
      visualization and delineation of end-stage kidneys. US, because its better
      availability and cost-benefit ratio, remains the method-of-choice compared to low
      field MR imaging in detecting cysts in multicystic kidneys. MR investigation is
      helpful in selected patients and may be used as an alternative.

PMID- 10937759
TI  - Detection and characterisation of renal lesions by multiphasic helical CT.
AB  - PURPOSE: The fast helical CT technique allows examination of the kidneys during
      different phases of contrast medium enhancement. However, every additional phase
      increases the radiation dosage to the patients. We investigated the detection
      rate and characterisation of renal lesions during different phases and evaluated
      them separately, and considered the possibility of excluding phases without loss
      of important information. MATERIAL AND METHODS: Sixty patients who underwent
      contrast-enhanced multiphasic renal helical CT examination were included. Every
      CT phase was evaluated separately. The number of lesions and the characteristics
      of the lesions were noted and all lesions were viewed together. RESULTS: A total
      of 153 cysts and 17 solid lesions were detected. The largest and an equal number
      of cysts (142/143) was detected in the nephrographic and excretory phases.
      However, the nephrographic phase detected more cortical cysts and the excretory
      phase detected more sinus cysts. All solid lesions were detected in all phases.
      Renal parenchymal tumours were best characterised in the cortical phase and
      angiomyolipomas in the native phase. CONCLUSION: The cortical phase was best for
      characterisation of renal parenchymal tumours. The nephrographic and excretory
      phases were best in detecting and characterising renal cysts. The nephrographic
      phase was the phase giving the least diagnostic information.

PMID- 10937760
TI  - Cranial epidural tuberculoma. A case report.
AB  - A 33-year-old patient with cranial epidural tuberculoma without history of
      tuberculosis is described. CT and MR imaging showed a lesion located on both
      sides of a right frontotemporal bone destruction with epidural extent. Except for
      a small necrotic core, the lesion enhanced intensely after contrast medium
      administration. Osteitis and subgaleal abscess were associated. The displaced
      dura mater delineated the epidural tuberculoma. Diagnosis was verified by
      histology and identification of Mycobacterium tuberculosis. After removal of the
      tuberculoma and combination therapy, there was a complete regression of
      abnormalities. Differential diagnoses are dural tuberculoma, focal tuberculous
      pachymeningitis and tuberculous epidural empyema.

PMID- 10937761
TI  - Intracardiac tumour and brain lesions in tuberous sclerosis. A case report of
      antenatal diagnosis by ultrasonography.
AB  - A case of antenatal tuberous sclerosis was diagnosed by ultrasonography.
      Intracardiac tumour (highly suspected rhabdomyoma) with transitory heart failure
      and multiple brain lesions were observed. After delivery, echocardiography,
      spiral CT and MR imaging diagnosis of tuberous sclerosis was confirmed by typical
      skin lesions (depigmented macules) and development of seizures.

PMID- 10937762
TI  - Chiasmatic glioblastoma of childhood. A case report.
AB  - A 6-year-old girl presented with visual deterioration that had progressively
      worsened over 2 months. MR imaging revealed a sellar, para- and suprasellar
      lesion. Subtotal tumor resection was performed. Histopathological diagnosis was
      glioblastoma of the optic chiasma. Chiasmatic glioblastoma is rare in adults and
      extremely uncommon in children. Surgical resection implies a risk of severe
      endocrinologic and ophthalmologic complications.

PMID- 10937764
TI  - Iodixanol and iohexol in cardioangiography. A comparative vectorcardiographic
      study.
AB  - PURPOSE: The non-ionic dimeric contrast medium (CM) iodixanol is isotonic with
      blood through the addition of electrolytes. In this study, we evaluated
      computerised dynamic vectorcardiography (VCG) as a tool in CM research by
      comparing the electrophysiological effects of iodixanol with those of the low
      osmolar CM iohexol. MATERIAL AND METHODS: A total of 119 patients referred for
      cardioangiography were included in this double-blind, randomised, parallel
      comparison of iodixanol (320 mg I/ml) and iohexol (350 mg I/ml). VCG was recorded
      and different VCG parameters were analysed. General tolerability, safety and
      radiographic efficacy were also assessed. RESULTS: Iodixanol induced less changes
      than iohexol in all VCG parameters and the sensation of warmth was significantly
      milder after iodixanol, but both CM were well tolerated. VCG might be useful in
      future studies to analyse electrophysiological effects caused by CM.

PMID- 10937763
TI  - Differentiated thyroid carcinomas. Prediction of tumor invasion with MR imaging.
AB  - PURPOSE: To assess diagnostic accuracy for tumor invasion of surrounding organs
      by measurement of tumor circumferences on MR images in patients with
      differentiated thyroid carcinomas. MATERIAL AND METHODS: Surgical and MR imaging
      findings in 50 patients with differentiated thyroid carcinoma (43 primary, 7
      recurrent lesions) were retrospectively reviewed. The degrees of circumference of
      tumor encroachment to the organs were measured, and the measurements and
      morphologic diagnosis of tumor invasion made by a head and neck radiologist were
      compared with surgical and pathologic findings using receiver operating
      characteristic curves. RESULTS: Diagnosis of tumor invasion by the radiologist
      was superior to the measurements of the carotid artery and cartilage, while the
      reverse was true for the trachea and esophagus. However, no statistical
      differences were noted between them for each structure. Optimal thresholds for
      tumor invasion were 90 degrees or more for the cartilage (94% accuracy) and
      esophagus (86% accuracy), 135 degrees or more for the trachea (86% accuracy), and
      225 degrees or more for the carotid artery (90% accuracy). CONCLUSION: Tumor
      invasion was more accurately diagnosed by measurement of tumor circumferences of
      each organ on MR images.

PMID- 10937765
TI  - Seasonal variation in the occurrence of late adverse skin reactions to iodine
      based contrast media.
AB  - PURPOSE: To study the possible seasonal effect in the occurrence of late adverse
      skin reactions to iodine-based contrast media (CM). MATERIAL AND METHODS: Data on
      4,875 adult patients followed for late adverse reactions after i.v. injections of
      iohexol or iopamidol, or intra-arterial injection of ioxaglate were
      retrospectively investigated with respect to the amount of global radiation vs.
      the occurrence of reactions. The information on these reactions was collected
      from questionnaires that were filled out by the patients (out-patients) or by
      nurses (in-patients). The follow-up time was 24 h. RESULTS: Fifty-two of 4,875
      patients (1.07%) had experienced a late skin reaction (urticaria or rash); this
      number exceeds the reports on spontaneous occurrence of such reactions by a
      factor of 300. Most of the reactions in a known location occurred on sun-exposed
      areas of the body. A 2-month peak in the incidence of reactions (May to June)
      included 35% of all events (p<0.025) and a 3-month peak (April to June) 46% of
      all events (p<0.01). There was a significant rank correlation (r = 0.613, p<0.05)
      between the frequency of reactions and the mean amount of global radiation.
      CONCLUSION: This study demonstrates a seasonal variation in skin reactions after
      intravascular injection of iodine-based CM. The possible photosensitising effect
      of these drugs should be further studied.

PMID- 10937767
TI  - Congenital laryngeal atresia: two autopsy cases, one describing the use of
      computed tomography.
AB  - Two autopsy cases of congenital laryngeal atresia (CLA) were studied. In the
      first case (a boy delivered at 37 weeks of gestation) the subglottic lumen was
      almost totally occupied by a dome shaped cricoid cartilage with a
      pharyngotracheal duct (PTD). No tracheoesophageal fistula (TEF) was found. In the
      second case (a girl born at 41 weeks of gestation) histology showed that the
      subglottic lumen was almost occluded by an epithelial lamina and a dome-shaped
      cricoid cartilage. Again no TEF was found. Both cases had PTD and showed normal
      development of the lungs. These deformities coincided with Smith & Bain's type II
      subglottic atresia. The anatomy of the lesion was confirmed by postmortem three
      dimensional reconstruction CT, the use of which has not previously been reported.

PMID- 10937766
TI  - Gadobenate dimeglumine and cerebral glucose metabolism. Continuous monitoring of
      striatal lactate levels in freely moving rats.
AB  - PURPOSE: Brain contrast-enhanced MR imaging reflects the leakage of contrast
      material into the brain tissue due to blood-brain barrier (BBB) disruption. The
      contact between brain tissue and contrast material requires a high level of
      neurotolerability of the contrast agent (CA). In the present study, we
      investigated the neurotolerability of the paramagnetic CA gadobenate dimeglumine,
      locally applied into the corpus striatum of freely moving rats, by evaluating its
      potential effects on cerebral glucose metabolism based on lactate levels.
      MATERIAL AND METHODS: Lactate levels were monitored using a microdialysis
      technique coupled with an enzyme reaction. A microdialysis probe for
      extracellular fluid sampling, together with a stainless steel cannula for CA
      administration, were inserted into the right corpus striatum of rats. Lactate
      levels were monitored for 2 h after gadobenate dimeglumine administration at 120
      nmol/rat, at fixed volume of 1.2 microl. The same volume of artificial
      cerebrospinal fluid (aCSF) was administered to control rats. RESULTS: Gadobenate
      dimeglumine did not induce any significant changes in the lactate striatal levels
      over the 30-min period after administration. Small, but significant, reductions
      in lactate concentration were found from the 45-min control point after
      gadobenate dimeglumine administration. Lactate response showed the same pattern
      in rats given aCSF. CONCLUSION: Gadobenate dimeglumine, intracerebrally
      administered, did not affect cerebral glucose metabolism in rats as it showed the
      same behaviour as aCSF on cerebral glucose utilization. The gradual attenuation
      in the endogenous lactate release observed 45 min after test compound
      administration is possibly due to a slight reduction in the probe recovery. The
      present findings confirm the neurotolerability of gadobenate dimeglumine
      previously shown in behavioural and electrophysiological studies.

PMID- 10937768
TI  - Expression and activity of matrix metalloproteinase-2 and -9 in experimental
      granulation tissue.
AB  - The restoration of functional connective tissue is a major goal of the wound
      healing process which is probably affected by matrix-modifying enzymes. To
      evaluate the spatial and temporal expression of matrix metalloproteinases (MMP)
      MMP-2 and MMP-9 and to study the regulation of MMP-2 in wound healing,
      subcutaneously implanted viscose cellulose sponges in rats were used to induce
      granulation tissue formation for up to 3 months. MMP-2 mRNA expression was seen
      throughout the experiment and it was highest after 2 months. MMP-9 gene
      expression was low between days 8-21 and increased after 4 weeks of granulation
      tissue formation. Membrane-type 1 MMP (MT1-MMP) mRNA was upregulated early and
      tissue inhibitor 2 of MMP (TIMP-2) mRNA later during wound healing. In in situ
      hybridization the expression of MMP-2 mRNA was seen mostly in fibroblast-like
      cells and MMP-9 mRNA in macrophage-like cells. MMP-9 immunoreactivity was
      detected in the polymorphonuclear leukocytes and macrophage-like cells on days 3
      8. MMP-9 proteolytic activity was observed only on days 3-8. The active form of
      the MMP-2 increased up to day 14, whereafter it remained at a constant level,
      whereas latent MMP-2 did not show any apparent changes during the experimental
      period. We conclude that MMP-2 is important during the prolonged remodelling
      phase, whereas the gelatinolytic activity of MMP-9 was demonstrated only in early
      wound healing, and the MMP-9 gene is upregulated when the granulation tissue
      matures.

PMID- 10937769
TI  - The immune response to chronic Pseudomonas aeruginosa lung infection in cystic
      fibrosis patients is predominantly of the Th2 type.
AB  - Most cystic fibrosis (CF) patients with chronic Pseudomonas aeruginosa lung
      infection have a persistent acute type lung inflammation dominated by
      polymorphonuclear neutrophils (PMN) and a pronounced antibody response against P.
      aeruginosa. We speculated whether this immune response in CF is of the Th2 type
      and whether a change to a Th1 type immune response could improve the prognosis.
      Therefore, we studied 14 CF patients with (CF +P) and 14 CF patients without (CF 
      P) chronic P. aeruginosa lung infection. The specific production of interferon
      gamma (IFN-gamma) and interleukin-4 (IL-4) by peripheral blood mononuclear cells
      was determined. Cells from CF +P patients had lower IFN-gamma (p<0.05) and higher
      IL-4 (p<0.005) production as compared to cells from CF -P patients. Furthermore,
      a positive correlation between IFN-gamma production and lung function was found
      (FVC: Rho = 0.637; p<0.03; FEV1: Rho=0.524; p<0.07). We conclude that a Th2 type
      immune response is most frequent in CF patients with chronic P. aeruginosa lung
      infection, and the patients with a Th1-dominated immune response had the best
      lung function. The clinical implication is that a change to a Th1 type immune
      response might improve the prognosis in these patients.

PMID- 10937770
TI  - Overexpression of human lecithin:cholesterol acyltransferase in mice offers no
      protection against diet-induced atherosclerosis.
AB  - Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the
      metabolism of cholesterol. We have used homozygous transgenic mice overexpressing
      the human LCAT transgene to study the effect of a "Western-type" atherogenic diet
      (30% fat, 5% cholesterol and 2% cholic acid) on their LCAT expression, activity,
      lipoprotein profile and tendency to develop atherosclerosis. The LCAT activity
      was 35-fold higher in serum of the homozygous transgenic mice than in murine
      control serum, and decreased 11-20% in the transgenic mice when fed the
      atherogenic diet. The total cholesterol and high-density lipoprotein cholesterol
      (HDL-C) concentrations were approximately doubled in the transgenic mice compared
      with the controls when both groups were fed a regular chow diet. In mice on the
      atherogenic diet, the triglyceride concentration decreased about 50% to the same
      level in transgenic and control mice. Total cholesterol and HDL-C concentrations
      increased and were 60-80% higher in the transgenic mice. The expression of LCAT
      mRNA in the liver was decreased by 49-60% in the transgenic mice when fed the
      atherogenic diet. The development of atherosclerosis was similar in transgenic
      and control mice. Thus, the 14- to 27-fold higher LCAT activity and the higher
      HDL-C concentrations in the homozygous LCAT transgenic mice had no significant
      protective influence on the development of diet-induced atherosclerosis.

PMID- 10937771
TI  - Enhancement of humoral and protective immune response induced by live-attenuated
      Salmonella typhi by ampicillin.
AB  - Efficacy of live-attenuated Salmonella vaccines delivered by the mucosal route is
      limited by the dose and interference from mucosal flora of the alimentary tract.
      In a mouse model, the total antibody response towards lipopolysaccharide of S.
      typhi was significantly enhanced at day 21 post-immunization with live-attenuated
      S. typhi (Ty21a) when ampicillin was concomitantly administered (p<0.005), and
      the lethal dose 50 of mice in the ampicillin and control groups immunized with
      Ty21a after wild-type S. typhi challenge on day 24 was 4x10(7) and 1x10(7),
      respectively. The faecal bacterial counts of the ampicillin group at days 1 and 3
      were significantly lower than those of the control group (p<0.01 and <0.05). On
      day 1, the number of mice with > or =10 Ty21a colonies isolated from the spleen
      was significantly higher in the ampicillin group than the control group (p<0.05).
      Furthermore, on the same day, Ty21a was isolated from the faeces of three mice
      from the ampicillin group, but only one from the control group. We conclude that
      ampicillin may have enhanced the humoral and protective immune responses by
      giving the Ty21a a selective advantage over the normal bacterial flora. This
      concept of antibiotic enhancement of immunization could have important
      implications for other live-attenuated vaccines, as well as the delivery of
      microbial antigens and DNA vaccines by live-attenuated Salmonella carriers.

PMID- 10937772
TI  - Lipid profiles of Helicobacter pylori colony variants.
AB  - A phase variation in Helicobacter pylori has been previously described. In one
      phase the bacterium had a cell wall lipid content typical for gram-negative
      bacteria (HpL), whereas in the other phase the bacterium was found to have a cell
      wall with increased amounts of lysophospholipids (HpS). The conversion is
      spontaneous, but could also be induced by acid (HpS(ind)) and was associated with
      in vitro release of Vac A and urease. The purpose of the present study was to
      determine the full phospholipid content of the cell wall to indicate a molecular
      mechanism of the colony variation. There were no appreciable differences between
      the lipid profiles of HpS and HpS(ind), while there were major differences
      between HpL and the S-variant. In the S-variant, lysophospholipids constituted
      about 50% of the total phospholipids, as compared to less than 2% in the L
      variant. The proportion of total and individual cholesteryl glucosides also
      showed considerable changes. HpL was dominated by the phosphate-linked
      cholesteryl glucoside (72%) while the acylated cholesteryl glucoside was the main
      cholesteryl glucoside of the S-variant (65%). Our results demonstrate a dramatic
      change in cell wall properties after acid induction and spontaneously in vitro,
      and suggest some molecular mechanisms for this variation from an in vitro non
      virulent to a virulent variant.

PMID- 10937773
TI  - Serological analysis of specific IgA to Chlamydia pneumoniae: increased
      sensitivity of IgA antibody detection using prolonged incubation and high antigen
      concentration.
AB  - The microimmunofluorescence technique (MIF) is recognized as the only test
      hitherto allowing discrimination between different Chlamydia species and is
      considered to be the reference method for serology. This method was developed for
      the detection of IgG and IgM antibodies only. We investigated the effects of some
      test parameters on the ability of MIF to detect Chlamydia pneumoniae IgA. These
      parameters were the time needed for binding of serum IgA to C. pneumoniae antigen
      and the effect of antigen concentration on the outcome of IgA antibody testing.
      It was found that the most sensitive MIF tests for the detection of serum IgA
      antibodies were those in which an overnight incubation of sera with antigen
      slides containing high concentrations of chlamydial elementary bodies was
      employed. The number of patients with chronic infections found to have elevated
      IgA titers was increased by 25% using longer incubation times for the antibody
      antigen reaction. Thirty-two sera from patients with coronary artery disease and
      confirmed chronic C. pneumoniae infection were used to compare antigen slides
      with low and high concentrations of elementary bodies with respect to IgA levels;
      31/32 patients were found to have specific IgA antibodies to C. pneumoniae using
      the high antigen concentration, as opposed to only 22/32 patients using the low
      antigen concentration.

PMID- 10937774
TI  - Nodular granulomatous Pneumocystis carinii pneumonia in a bone marrow transplant
      recipient. Case report.
AB  - We report a case of nodular granulomatous Pneumocystis carinii pneumonia
      following bone marrow transplantation. The patient was a 40-year-old man who had
      undergone bone marrow transplantation for myeloblastic acute leukemia. He
      presented with fever, dyspnea and bilateral diffuse nodular infiltration of the
      lungs. Bronchoalveolar lavage was negative. Open lung biopsy was performed.
      Histological examination revealed a granulomatous reaction with central necrosis
      surrounded by epithelioid and giant cells. Toluidine blue and Gomori-Grocott
      stains identified a few P. carinii. Mycobacterial and fungal cultures were
      negative. A granulomatous reaction is rarely observed and almost only in HIV
      infected patients. To our knowledge this is the first description in a bone
      marrow transplant recipient.

PMID- 10937775
TI  - Expression of stanniocalcin in zona glomerulosa and medulla of normal human
      adrenal glands, and some adrenal tumors and cell lines.
AB  - Stanniocalcin (STC) is a calcium (Ca)-regulating hormone that was originally
      discovered in the fish Stannius body, which is a unique endocrine organ.
      Hypercalcemia increases STC secretion, which inhibits Ca uptake by the gills and
      normalizes serum Ca level. In this study we investigated the STC expression in
      human normal and abnormal adrenal cells. Immunohistochemistry using monoclonal
      antibody against STC revealed specific staining in zona glomerulosa and medulla
      of normal human adrenal glands. STC was also detected in human adrenal tumors,
      such as pheochromocytoma, differentiated neuroblastoma, and aldosterone-producing
      adenoma, and cultured adrenal tumor cells (rat pheochromocytoma PC-12 cells and
      human neuroblastoma NB-1 cells). However, undifferentiated human adrenal
      neuroblastoma was negative for STC staining. Reverse transcription polymerase
      chain reaction demonstrated STC mRNA expression in cultured PC-12 cells and NB-1
      cells. Following several studies indicating that zona glomerulosa cells of
      adrenal glands express neuroendocrine properties, STC expression in normal and
      abnormal adrenal cells provides additional evidence to support the neuroendocrine
      differentiation of these cells. In conclusion, STC may be useful as a new cell
      marker of adrenal glands under physiological and pathological conditions.

PMID- 10937776
TI  - A new model for evaluation of thrombosis and ischaemia/reperfusion injury.
AB  - BACKGROUND: The purpose of the present study was to describe infarct size and
      platelet accumulation when reperfusion injury was combined with a thrombogenic
      lesion in the coronary artery. The left anterior descending artery was damaged in
      11 pigs and subsequently occluded proximal to the lesion for 50 min, followed by
      4 h of reperfusion. RESULTS: The infarct size/area at risk was 40 (35 63)%.
      Infarct size correlated with troponin-T-3 h (p=0.85, p<0.002), but not with
      creatine kinase-3 h. Platelet aggregation decreased by 34% (p<0.01) at 15 min of
      reperfusion, but returned to baseline. Platelet accumulation in the left
      ventricle was significantly higher in the area at risk (194 (157-206)%) compared
      to the right ventricle (137 (120-142)%); p<0.05). CONCLUSION: A decreased
      platelet reactivity and increased accumulation of platelets in the area at risk
      indicates that activated platelets become entrapped in the myocardium. Troponin-T
      was a better marker of myocardial damage than creatine kinase in this in vivo
      model with pigs.

PMID- 10937777
TI  - Interobserver variation in diagnosing coeliac disease. A joint study by Danish
      and Swedish pathologists.
AB  - There is an almost 40-fold difference in incidence rates of symptomatic coeliac
      disease between Denmark and Sweden. In an attempt to explain this difference, the
      present study focused on the interobserver agreement when pathologists were
      assessing small intestinal biopsy specimens from children suspected of suffering
      from coeliac disease. The study was performed on 90 biopsy specimens from 73
      children. Most of the biopsies came from children who turned out not to suffer
      from coeliac disease after a clinical evaluation including small intestinal
      biopsy. Using the kappa methodology, the interobserver agreement between two
      Danish pathologists and one Swedish pathologist, all of whom were experienced,
      was "moderate" to "substantial" or 0.57-0.75. Kappa indices when the pathologists
      evaluated selected histological elements were in the interval from 0.24 to 0.67.
      A comparison of a previous routine diagnostic assessment of the 90 biopsies (14
      pathologists) with the results of the experienced pathologists in the present
      study gave kappa indices of from 0.53 to 0.57. The study could prove no major
      differences in the histopathological assessment of small intestinal biopsy
      specimens made by Danish and Swedish pathologists. The difference in clinical
      presentation of coeliac disease in Denmark and Sweden does not relate to
      differences in the histopathological assessment of small intestinal biopsies.

PMID- 10937778
TI  - Detection and identification of fungi in blood using broad-range 28S rDNA PCR
      amplification and species-specific hybridisation.
AB  - The aim of the present study was to develop a PCR-based method to detect and
      identify fungi directly from human venous blood. We used broad-range PCR primers
      that targeted a part of the large subunit 28S rRNA genes. To obtain species
      specific hybridisation probes, type strains of Candida albicans, C. glabrata, C.
      krusei, C. parapsilosis, C. tropicalis and Cryptococcus neoformans were PCR
      amplified, and the amplicons were analysed by gene sequencing. Based on the
      sequence analysis, species-specific probes that targeted variable regions were
      designed and used in hybridisation analyses. Between 2 to 10 fungal cells/ml of
      spiked blood samples could be detected and correctly identified to species. We
      applied the technique to blood samples obtained from two patients with or two
      patients without verified candidaemia. The three samples of candidaemia patients
      were correctly identified to species level, and those of the negative patients
      remained negative. This method is a potential tool for diagnosis of systemic
      invasive candidiasis.

PMID- 10937779
TI  - Violence in psychiatry, view-points for standardized research.

PMID- 10937780
TI  - Family interventions in schizophrenia and related disorders: a critical review of
      clinical trials.
AB  - OBJECTIVE: To update evidence from studies on family intervention in
      schizophrenia looking carefully at methodological issues. METHOD: Twenty-five
      studies were reviewed, using specific outcome criteria, and computing effect
      sizes whenever possible. RESULTS: Effect on relapse is relatively well assessed,
      although differences emerged particularly in comparison with poor control
      treatments and disappeared in recent studies. Findings on patient's symptoms,
      social functioning or family variables are limited and affected by methodological
      pitfalls. No difference between intervention models emerged, although
      behavioural/psycho-educational approaches were better investigated. Patients'
      inclusion, greater frequency and length of treatment led to better results. The
      main flaws were: poor control of standard treatment, small sample sizes, failure
      in evaluating clinical significance in continuous outcome variables. CONCLUSION:
      It remains unclear whether the effect depends on family treatment or on more
      intensive care. The failure to relate outcome to family-mediating variables is a
      challenge to the rationale underlying family interventions.

PMID- 10937781
TI  - Patient education in schizophrenia: a review.
AB  - OBJECTIVE: To identify and analyse methodology and results of studies of patient
      education in schizophrenia. METHOD: A literature search was made in the databases
      Medline, Excerpta Medica, Psychlit and Cinahl. RESULTS: Most studies demonstrate
      that knowledge and compliance can be improved by educational interventions.
      Compliance seems to be most readily influenced by interventions including
      behavioural components. A few studies indicate that relapse and symptomatology
      can be influenced by educational interventions as well. No influence of the
      duration of interventions was found. Where educability is studied, age,
      medication and level of symptoms are potential predictors. CONCLUSION: Due to
      methodological limitations and insufficient reporting the results of available
      studies on patient education in schizophrenia are far from conclusive. The
      demonstration of the efficacy of patient education in improving knowledge and
      compliance is most consistent.

PMID- 10937782
TI  - Measurement of violence during in-patient treatment and association with
      psychopathology.
AB  - OBJECTIVE: Four available instruments for the measurement of violence were
      compared. The association between psychopathological status at admission and
      violence during in-patient treatment was examined. METHOD: In 199 consecutively
      admitted patients (143 with schizophrenia or schizoaffective disorder, 56 with
      non-psychotic disorders), the PANSS was recorded at the time of admission.
      Violent behaviour against self and others was assessed for the total period of in
      patient treatment using the scales MOAS, SDAS, SOAS and VS. RESULTS: The
      sumscores of the scales correlated highly (r between 0.78 and 0.91), but the
      scales differed in sensibility and inter-rater reliability. There was a strong
      association between thought disorders and violent behaviour during in-patient
      treatment in psychotic patients (beta = 0.34; P<0.001). CONCLUSION: Although
      constructed to measure different aspects of violence, all investigated
      instruments correlated highly. The psychopathological status at admission is
      associated with violent behaviour during in-patient treatment.

PMID- 10937783
TI  - Suicide prevention--a medical breakthrough?
AB  - OBJECTIVE: The author hypothesized, based on research until 1991, that a five
      fold increase in the use of antidepressants might reduce Swedish suicide rates by
      25%. A subsequent 3.5-fold increase in the use of antidepressants provided a
      'natural experimental situation' for prospectively testing this hypothesis.
      METHOD: Swedish statistics on suicide, use of antidepressants, unemployment and
      alcohol consumption were obtained for 1978-96. Time-series of the latter
      variables were compared with suicide rates. Demographic subgroups regarding age,
      gender and county were analysed. Suicide rates were also compared with the use of
      antidepressants in Denmark, Norway and Finland. RESULTS: Suicide rates decreased
      in accordance with the a priori hypothesis. Alcohol consumption and unemployment
      rates did not correlate well with suicide rates. CONCLUSION: This naturalistic
      study is not conclusive. The increased use of antidepressants appears, however,
      to be one of the contributing factors to the decrease in the suicide rate. It is
      of great scientific and clinical importance that this be evaluated by further
      studies.

PMID- 10937784
TI  - Suicide attempts and personality disorder.
AB  - OBJECTIVE: The purpose of the present study was to compare clinical
      characteristics of suicide attempters with or without personality disorders.
      METHOD: A systematic sample (n = 114) of patients from consecutive cases of
      attempted suicide referred to general hospitals in Helsinki was interviewed and
      diagnosed according to DSM-III-R. Forty-six subjects with DSM-III-R personality
      disorders were identified and divided into clusters A (n = 4), B (n = 34) and C
      (n = 8). These subjects were compared with 65 suicide attempters without
      personality disorders in terms of clinical characteristics and treatment
      received. RESULTS: Suicide attempters with personality disorders more often had a
      history of previous suicide attempts and lifetime psychiatric treatment than
      comparison subjects. However, suicide attempts did not differ in terms of suicide
      intent, hopelessness, lethality or impulsiveness between subjects with or without
      personality disorders. CONCLUSION: Although suicidal behaviour is a more
      persistent feature among those with personality disorders, their clinical
      characteristics at the time of a suicide attempt may not differ from those
      without personality disorders.

PMID- 10937785
TI  - Contacts to the health care system prior to suicide: a comprehensive analysis
      using registers for general and psychiatric hospital admissions, contacts to
      general practitioners and practising specialists and drug prescriptions.
AB  - OBJECTIVE: The purpose of this study was to describe suicides' contacts with
      various parts of the health-care system. METHOD: Data on 472 people who committed
      suicide in a Danish County (Funen) in the period of April 1 1991 to December 31
      1995 were searched in the Danish Psychiatric Central Register, the National
      Patient Register, the National Health Insurance and Odense Pharmacoepidemiologic
      Database. RESULTS: In total, 97.5% of the suicides were recaptured in at least
      one of these registers. Forty-two per cent had been hospitalized in psychiatric
      departments. Within the last month before death, 66% consulted a general
      practitioner, 13% and 7%, respectively, were discharged from a psychiatric
      hospital and general hospital. CONCLUSION: The registers used provided a
      comprehensive registry-based description of suicides' contacts with the health
      care system. The most prominent features were the high prevalence of psychiatric
      morbidity and the high rate of contacts with GPs close to suicide.

PMID- 10937786
TI  - Death wishes in the very elderly: data from a 3-year follow-up study.
AB  - OBJECTIVE: The aim of this study was to study the 3-year outcome of death wishes
      in an elderly population. METHOD: 1099 very elderly people were examined
      extensively by physicians, including a structured psychiatric interview. Three
      years later those who had survived were re-examined (n = 683) using a similar
      procedure. RESULTS: Of the sample, 11.6% (n = 128) had death wishes at the first
      examination and 8.9% (n = 54) at the follow-up. Of the 54, 17 have had death
      wishes persistently during the 3-year period; all of them had psychiatric
      diagnoses. Of those having death wishes at one of the examinations 70% had
      psychiatric diagnoses. Attrition was more common in the group with death wishes
      than in the group without when age, gender, somatic disorders including dementia
      and disability in daily living were taken into account. CONCLUSION: This study
      shows that there is a need for a psychiatric examination when elderly people
      express death wishes.

PMID- 10937787
TI  - The construction of the SEDAS: a new suicide-attitude questionnaire.
AB  - OBJECTIVE: Only two scales exist for measuring attitudes towards suicidal
      behaviour. Because of theoretical and methodological limitations of both scales,
      the SEDAS was constructed to offer an alternative instrument. METHOD: The
      semantic differential scale, from which the SEDAS was devised, consisted of 36
      items (pairs of adjectives) constructed to measure attitudes towards suicidal
      behaviour of different actors in various situations. It was administered to 142
      Dutch SOS-telephone volunteers for seven different actor/situation sets. RESULTS:
      Item analysis reduced the number of suitable items to 15. Simultaneous component
      analysis revealed two dimensions on which the actor/situation sets were scored:
      health/illness and acceptance/rejection, jointly accounting for 47% of variance.
      Psychometrics of the instrument in terms of internal consistency (values between
      0.70 and 0.86), item-rest correlation and test-retest correlation (between 0.63
      and 0.87) are acceptable to good. CONCLUSION: The SEDAS may be of value in
      population surveys, and facilitate effect evaluation of staff training and
      suicide prevention programmes.

PMID- 10937788
TI  - Comparison of the standard and the computerized versions of the Symptom Check
      List (SCL-90-R): a randomized trial.
AB  - OBJECTIVE: The purpose of this study was to examine whether computer
      administration of the Symptom Check List (SCL-90-R) is equivalent to paper-and
      pencil originals. METHOD: 282 psychosomatic outpatients were randomly assigned to
      computer or paper-and-pencil conditions. Statistical equivalence tests were used
      to examine psychometric equivalence for the means. Reliabilities and correlations
      were compared for the two methods of administration. RESULTS: No systematic
      differences were observed in group means for most of the subscales. Subjects of
      the computer-administered group scored higher on the SCL-90-R subscale 'Obsessive
      Compulsive' and 'Anger-Hostility' than the control subjects. Gender and
      administration mode interaction was observed for one subscale, while age and
      administration interaction was observed for another subscale. CONCLUSION: Using
      computer-administered tests makes administration and scoring of tests more
      efficient. The differences between the two administration modes were small,
      although noticeable. Further research is needed to determine whether computer
      environment, computer experience and age may influence the test results.

PMID- 10937789
TI  - Granulocyte colony-stimulating factor plasma levels during clozapine- and
      olanzapine-induced granulocytopenia.
AB  - OBJECTIVE: Recent case studies suggest that impaired granulopoiesis, well-known
      to occur during clozapine treatment, may also be observed when olanzapine is
      administered. The underlying mechanisms are unknown, but haematopoietic cytokines
      such as granulocyte colony-stimulating factor (G-CSF) are likely to be involved.
      METHOD: We measured the plasma levels of G-CSF and of other cytokines
      longitudinally in a female patient who developed granulocytopenia twice, first
      during clozapine treatment and again when olanzapine was administered. RESULTS: G
      CSF levels, but not those of other cytokines, closely paralleled granulocyte
      counts, yielding a significant positive correlation. G-CSF was not detectable in
      plasma when granulocytopenia occurred. Granulocytopenia resolved spontaneously
      despite continuing treatment with olanzapine. CONCLUSION: The present case
      suggests that clozapine and olanzapine both are able to induce transient
      granulocytopenia through a similar or common mechanism that does not involve a
      compensatory increase in G-CSF levels.

PMID- 10937790
TI  - De novo sequencing of proteolytic peptides by a combination of C-terminal
      derivatization and nano-electrospray/collision-induced dissociation mass
      spectrometry.
AB  - A series of synthetic peptides (3-15 residues), C-terminally derivatized with 4
      aminonaphthalenesulfonic acid (ansa), have been analyzed on a hybrid magnetic
      sector-orthogonal acceleration time-of-flight tandem mass spectrometer, fitted
      with a nano-electrospray (nano-ES) interface. Deprotonated molecules generated by
      negative-ion ES were subjected to collision-induced dissociation (CID) using
      either methane or xenon as the collision gas, at a collision energy of 400 eV
      (laboratory frame of reference). As a consequence of charge localization on the
      sulfonate group, only C-terminal fragment ions were formed, presumably by charge
      remote fragmentation mechanisms. Interpretable CID spectra were obtained from
      fmol amounts of the small peptides (up to 6 residues), whereas low pmol amounts
      were required for the larger peptides. CID spectra were also recorded of
      derivatized, previously noncharacterised peptides obtained by proteolysis of
      cytosolic hamster liver aldehyde dehydrogenase. Interpretation of these CID
      spectra was based on rules established for the fragmentation of the synthetic
      peptides. This study shows that derivatization with ansa may be useful in the de
      novo sequencing of peptides.

PMID- 10937791
TI  - The fragmentation pathways of protonated glycine: a computational study.
AB  - Numerous studies have demonstrated that protonated aliphatic amino acids,
      [H2NCHRCO2H + H]+, fragment in the gas phase to form iminium ions, H2N=CHR+.
      Unfortunately none of these studies have probed the structure of the neutral(s)
      lost as well as the mechanism of fragmentation. Three main mechanisms have been
      previously proposed: (1) loss of the combined elements of H2O and CO; (2) loss of
      dihydroxycarbene (HO)2C: and (3) loss of formic acid, HC(=O)OH. Herein, ab initio
      and density functional theory calculations have been used to calculate the key
      reactants, transition states, and products of these and several other competing
      reaction channels in the fragmentation of protonated glycine. The loss of the
      combined elements of H2O and CO is thermodynamically and kinetically favored over
      the alternative formic acid or (HO)2C fragmentation processes.

PMID- 10937792
TI  - Acyclic distonic acylium ions: dual free radical and acylium ion reactivity in a
      single molecule
AB  - Three gaseous acyclic distonic acylium ions: *CH2-CH2-C+=O, *CH2-CH2-CH2-C+=O,
      and *CH2=C(CH2)-C+=O, are found to display dual free radical and acylium ion
      reactivity; with appropriate neutrals, they react selectively either as free
      radicals with inert charge sites, or (and more pronouncedly) as acylium ions with
      inert radical sites. The free radical reactivity of the ions is demonstrated via
      the Kenttamaa reaction: CH3S* abstraction with the spin trap dimethyl disulfide;
      their ion reactivity by two reactions most characteristic of acylium ions:
      transacetalization with 2-methyl-1,3-dioxolane and the gas-phase Meerwein
      reaction, that is, expansion of the three-membered epoxide ring of
      epichlorohydrin to the five-membered 1,3-dioxolanylium ion ring. In "one-pot"
      reactions with gaseous mixtures of epichlorohydrin and dimethyl disulfide, the
      ions react selectively at either site, but more readily at the acylium charge
      site, to form the two mono-derivatized ions. Further reaction at either the
      remaining free radical or acylium charge site forms a single bi-derivatized ion
      as the final product. Becke3LYP/6-31G(d) calculations predict the reactions at
      the acylium charge sites of the three distonic ions to be highly exothermic, and
      both the "hot" transacetalization and epoxide ring expansion products of *CH2-CH2
      CH2-C+=O to dissociate rapidly by H2C=CH2 loss in overall exothermic processes.
      The calculations also predict highly spatially separate odd spin and charge sites
      for the novel cyclic distonic ketal ions formed by the reactions at the acylium
      charge sites.

PMID- 10937793
TI  - The
AB  - The bimolecular reaction of the CH2CHOH+ enol ion (m/z 44) with acetaldehyde
      gives a strongly dominant product, m/z 45, formed mainly by proton transfer from
      the ion to the molecule. The abundance of the product coming from a H*
      abstraction reaction from the neutral, albeit more exothermic, is negligible. In
      order to explain this result, the long lived [CH2CHOH*+, CH3CHO] solvated ion was
      generated by reaction of the CH2CHOH*+ enol ion with (CH3CHO)n in the cell of a
      Fourier transform ion cyclotron resonance mass spectrometer. The structure of
      this solvated ion was clearly established. Labeling indicates that [CH2CHOH+,
      CH3CHO], upon low energy collisions, reacts by H* abstraction more rapidly than
      by H+ transfer to the neutral moiety. This shows that the entropic factors are
      determinant when the enol ion reacts directly with acetaldehyde.

PMID- 10937794
TI  - Gas-phase H/D exchange reactions of polyamine complexes: (M + H)+, (M + alkali
      metal+), and (M + 2H)2+
AB  - Gas-phase hydrogen/deuterium exchange reactions between noncovalent polyamine
      complexes and D2O, CH3OD, or ND3 are undertaken in a quadrupole ion trap mass
      spectrometer. Structural features of the protonated polyamines can be
      differentiated by the rates and overall extent of exchange, specifically the
      presence of propylene units and/or a cyclic structure noticeably decreases
      exchange compared to the exchange observed for acyclic polyamines with only
      ethylene bridges between amino groups. Significant differences are observed for
      singly protonated vs. doubly protonated complexes, where the doubly protonated
      complexes undergo more efficient exchange at a higher rate than the analogous
      singly protonated complexes. Molecular modeling calculations suggest that more
      diffuse conformations may exist for the higher charge states, thus facilitating
      H/D exchange. In addition, H/D exchange reactions between the alkali metal
      cationized complexes and ND3 are nearly quenched, compared to the significant
      exchange seen for singly protonated complexes. A conformational change or the
      loss of a low energy reaction pathway may explain the limited exchange reactions
      seen when a bulky cation replaces a proton in the complex.

PMID- 10937796
TI  - Application of nonpolar matrices for the analysis of low molecular weight
      nonpolar synthetic polymers by matrix-assisted laser desorption/ionization time
      of-flight mass spectrometry
AB  - The application of nonpolar matrices for the analysis of low molecular weight
      nonpolar synthetic polymers using matrix-assisted laser desorption/ionization
      mass spectrometry (MALDI-MS) is demonstrated. Anthracene, pyrene, and
      acenaphthene were utilized as nonpolar matrices for the analysis of
      polybutadiene, polyisoprene, and polystyrene samples of various average molecular
      weights ranging from about 700 to 5,000. The standard MALDI-MS approach for the
      analysis of these types of polymers involves the use of conventional acidic
      matrices, such as all-trans-retinoic acid, with an additional cationization
      reagent. The nonpolar matrices used in this study are shown to be as equally
      effective as the conventional matrices. The uniform mixing of the nonpolar
      matrices and the nonpolar analytes enhances the MALDI-MS spectral
      reproducibility. Silver salts were found to be the best cationization reagents
      for all of the cases studied. Copper salts worked well for polystyrene, poorly
      for polyisoprene, and not at all for polybutadiene samples. These matrices should
      be useful for the characterization of hydrocarbon polymers and other analytes,
      such as modified polymers, which may potentially be sensitive to acidic matrices.

PMID- 10937795
TI  - Electrospray and atmospheric pressure chemical ionization tandem mass
      spectrometric behavior of eight anabolic steroid glucuronides.
AB  - Mass spectrometric and tandem mass spectrometric behavior of eight anabolic
      steroid glucuronides were examined using electrospray (ESI) and atmospheric
      pressure chemical ionization (APCI) in negative and positive ion mode. The
      objective was to elucidate the most suitable ionization method to produce intense
      structure specific product ions and to examine the possibilities of
      distinguishing between isomeric steroid glucuronides. The analytes were
      glucuronide conjugates of testosterone (TG), epitestosterone (ETG), nandrolone
      (NG), androsterone (AG), 5alpha-estran-3alpha-ol-17-one (5alpha-NG), 5beta-estran
      3alpha-ol-17-one (5beta-NG), 17alpha-methyl-5alpha-androstane-3alpha,17beta-diol
      (5alpha-MTG), and 17alpha-methyl-5beta-androstane-3alpha,17beta-diol (5beta-MTG),
      the last four being new compounds synthesized with enzyme-assisted method in our
      laboratory. High proton affinity of the 4-ene-3-one system in the steroid
      structure favored the formation of protonated molecule [M + H]+ in positive ion
      mode mass spectrometry (MS), whereas the steroid glucuronides with lower proton
      affinities were detected mainly as ammonium adducts [M + NH4]+. The only ion
      produced in negative ion mode mass spectrometry was a very intense and stable
      deprotonated molecule [M - H]- . Positive ion ESI and APCI MS/MS spectra showed
      abundant and structure specific product ions [M + H - Glu]+, [M + H - Glu -
      H2O]+, and [M + H - Glu - 2H2O]+ of protonated molecules and corresponding ions
      of the ammonium adduct ions. The ratio of the relative abundances of these ions
      and the stability of the precursor ion provided distinction of 5alpha-NG and
      5beta-NG isomers and TG and ETG isomers. Corresponding diagnostic ions were only
      minor peaks in negative ion MS/MS spectra. It was shown that positive ion ESI
      MS/MS is the most promising method for further development of LC-MS methods for
      anabolic steroid glucuronides.

PMID- 10937797
TI  - Investigation of bovine ubiquitin conformers separated by high-field asymmetric
      waveform ion mobility spectrometry: cross section measurements using energy-loss
      experiments with a triple quadrupole mass spectrometer.
AB  - High-field asymmetric waveform ion mobility spectrometry (FAIMS) was used to
      separate gas-phase conformers of bovine ubiquitin produced by electrospray
      ionization. These conformers were sampled by a triple quadrupole mass
      spectrometer where energy-loss experiments, following the work of Douglas and co
      workers, were used to determine their cross sections. The measured cross sections
      for some conformers were readily altered by the voltages applied to the interface
      ion optics, therefore very gentle mass spectrometer interface conditions were
      required to preserve gas-phase conformers separated by FAIMS. Cross sections for
      19 conformers (charge states +5 through +13) were measured. Two conformers for
      the +12 charge state, which were readily separated in FAIMS, were found to have
      similar cross sections. Based on a method to calibrate the collision gas
      thickness, the cross sections measured using the FAIMS/energy-loss method were
      compared with literature values determined using drift tube ion mobility
      spectrometry. The comparison illustrated that the conformers of bovine ubiquitin
      that were identified using drift tube ion mobility spectrometry were also
      observed using the FAIMS device.

PMID- 10937798
TI  - Preservation and detection of specific antibody--peptide complexes by matrix
      assisted laser desorption ionization mass spectrometry.
AB  - The direct detection of an antibody-peptide complex is reported by matrix
      assisted laser desorption ionization mass spectrometry (MALDI-MS). Experimental
      conditions have been found in which specific, noncovalent interactions in
      solution are maintained throughout the sample preparation and ionization process.
      Mass measurements based on the ion signals for the intact antibody and 1:1
      antibody-peptide complex reveal that specific noncovalent associations between a
      monoclonal antibody and a peptide, which comprises the determinant of the
      corresponding antigen, are maintained in the gas phase. These results support the
      wider application of MALDI-MS to studies of the structure and specificity of
      macromolecular complexes important to immune and other biological function.

PMID- 10937799
TI  - Fibrinolysis: an unfinished agenda.
AB  - There has been a recent decline in interest in fibrinolysis, suggesting that its
      physiological basis is sufficiently understood and that therapeutic thrombolysis
      has reached its limit. The importance of the subject has not diminished since
      cardiovascular disease is now a leading health problem even in developing
      countries. Certain highlights and inconsistencies are reviewed. The clinical
      trials of tissue plasminogen activator (t-PA) revealed a major discrepancy
      between its fibrinolytic efficacy and its clinical benefit (the 't-PA paradox')
      that is unexplained. Dose-finding studies also showed that the fibrinolytic
      efficacy of t-PA required significant nonspecific plasminogen activation.
      Furthermore, the longstanding belief that t-PA is responsible for physiological
      fibrinolysis and urokinase-type PA (u-PA) for pericellular plasminogen activation
      is belied by extensive experimental animal data, but these findings have had
      little impact on traditional thinking. As a result, the mechanisms responsible
      for the u-PA paradigm of fibrinolysis have received little attention. Clinical
      experience with pro-u-PA remains limited and most clinical trials have used
      infusion rates at which pro-u-PA is largely converted systemically to urokinase.
      This is due to the unanticipated instability of pro-u-PA in plasma at
      pharmacological concentrations. Insufficient understanding of basic mechanisms of
      fibrinolysis has handicapped the design of chimeric or mutant activators. It is
      submitted that physiological fibrinolysis remains to be better defined, and that
      it is premature to conclude that therapeutic thrombolysis will be inevitably
      accompanied by side effects that undermine this method of inducing reperfusion.

PMID- 10937800
TI  - The effect of prolil-glycil-proline (PGP) peptide and PGP-rich substances on
      haemostatic parameters of rat blood.
AB  - The effect of intravenous and intranasal administration of proline-containing
      peptide, especially prolil-glycil-proline (PGP), on the haemostatic system of
      rats was investigated. Tripeptide PGP after single intravenous (0.2, 1.0 and 1.5
      mg/kg) or intranasal (0.5 mg/ kg) administration increased (P < 0.05) total
      fibrinolytic and fibrin depolymerizating (FDA) activities, and tissue plasminogen
      activator levels (t-PA), and decreased the plasmin inhibitors (PI) and activated
      factor XIII (factor XIIIa) levels in blood plasma. Repeated daily intranasal
      administration (5 days) of PGP produced a significant increase of anticoagulant
      and fibrinolytic activities (P < 0.05), and a decrease of platelet aggregation,
      PI and factor XIIIa levels in blood plasma. Fibrinogen concentrations remained
      practically unchanged. Chronic peroral administration of gelatin (protein
      particularly rich of PGP, prolil-glycil, glycil-proline) as a food supplement
      significantly increased t-PA level (by 120%) at day 10 and FDA (by 290%) at day
      14 in blood plasma. We also observed potent suppression of thrombus formation
      (venous thrombosis model) by intranasal PGP administration. Therefore, PGP and
      some PGP-rich substances can be qualified as potent anticoagulant and
      antithrombotic agents.

PMID- 10937801
TI  - Factor VII R110C: a novel missense mutation (Arg110Cys) in the second epidermal
      growth factor-like domain causing factor VII deficiency in members of a Japanese
      family.
AB  - This report describes the findings of a genetic analysis of the factor VII (FVII)
      gene in a Japanese, male patient with FVII deficiency. The proband showed FVII
      activity level of 25% and FVII antigen level of 28% of the normal value, but he
      had no severe bleeding episodes. We identified the mutation by direct sequencing
      of polymerase chain reaction products representing all exons except 1b and their
      flanking intronic regions of his FVII gene. We detected a single point mutation,
      a C-->T substitution at nucleotide position 7863 in exon 5, which results in an
      amino acid replacement of Arg (CGC) to Cys (TGC) at codon 110 in the second
      epidermal growth factor-like domain. Homozygosity was confirmed in the propositus
      by loss of a site for the restriction endonuclease Eco47III. Furthermore, his
      parents, who had moderately reduced levels of factor VII activity and antigen,
      carried this mutation site as a heterozygote. Although the Arg11O residue is
      located distal to the tissue factor (TF) in the soluble TF-FVIIa crystal
      structure, we infer that the replacement of the positively charged and larger Arg
      residue with a neutral Cys residue may be likely to impair proper folding,
      resulting in destabilization of the protein structure.

PMID- 10937802
TI  - Fatal pulmonary artery thrombosis in a patient with Behcet's disease, activated
      protein C resistance and hyperhomocystinemia.
AB  - Behcet's disease (BD) is known for its tendency for thromboembolism, which is
      thought to be due to vascular injury. The important role of inherited
      thrombophilias is now becoming increasingly clear. However, conflicting data
      exist in terms of the contribution of these factors to the thrombotic risk in BD.
      In this case report, we describe a patient with BD who presented with severe cor
      pulmonale due to recurrent chronic venous thromboembolism and pulmonary artery
      thrombosis. The biochemical evaluation revealed that the patient was homozygotic
      for the factor V Leiden (R506Q) mutation and had increased levels of
      homocysteine. His condition deteriorated despite adequate anticoagulation
      treatment, and he died suddenly after 7 months of follow-up. We assume that the
      presence of thrombophilic risk factors augments and synergizes with the
      hypercoagulable state already existing in BD, leading to fatal thrombosis in this
      patient.

PMID- 10937803
TI  - Effects of the glycoprotein IIb/IIIa receptor antagonist c7E3 Fab and
      anticoagulants on platelet aggregation and thrombin potential under high
      coagulant challenge in vitro.
AB  - The present study was performed to investigate the combined effects of the
      platelet glycoprotein IIb/IIIa receptor antagonist c7E3 Fab (abciximab) and the
      anticoagulants unfractionated heparin (UH), low molecular weight heparin (LMWH),
      and recombinant hirudin (rH) on platelet aggregation and thrombin generation
      under high coagulant challenge by extrinsic activation of platelet-rich plasma.
      Platelet aggregation and thrombin generation were assessed simultaneously in the
      presence of different concentrations of abciximab and anticoagulants. Increasing
      concentrations of abciximab resulted in a dose-dependent anti-aggregating effect
      with a maximum at 20 microg/ml. Doses of 5, 10, and 20 microg/ml abciximab
      prolonged the lag phase until the onset of platelet aggregation, but this effect
      was independent of the dosage used. Abciximab had no influence on the thrombin
      potential under our high coagulant challenge. UH, LMWH, and rH showed a dose
      dependent prolongation of the lag phase until the onset of platelet aggregation
      and decreased the thrombin potential. Addition of anticoagulants did not
      contribute to further inhibition of platelet aggregation in the presence of
      abciximab, but the combination of abciximab and anticoagulants exhibited an
      additive effect on prolongation of the lag phase until the onset of platelet
      aggregation. Addition of abciximab to anticoagulants did not result in further
      decrease of the thrombin potential. Our study demonstrates the respective
      specific effects of abciximab and anticoagulants on platelet aggregation and
      thrombin potential under high coagulant challenge, and also an additive effect of
      abciximab and the anticoagulants UH, LMWH, and rH on the lag phase until the
      onset of platelet aggregation.

PMID- 10937804
TI  - Systemic activation of coagulation and fibrynolysis in a porcine model of
      serogroup A streptococcal shock.
AB  - In a porcine model of Gram-positive sepsis, 28 juvenile pigs were studied to
      evaluate the effect of a continuous infusion of live serogroup A streptococci
      (GAS) on the activation of coagulation and fibrinolysis. Plasma levels of
      thrombin-antithrombin (TAT) complexes, tissue plasminogen activator (t-PA) and
      plasminogen activator inhibitor-1 (PAI-1) activities were measured using
      commercially available kits. The continuous infusion of GAS [(3-5) x 10(8) colony
      forming units/kg per h] caused early signs of severe septicaemia in the pigs,
      with pulmonary hypertension, systemic hypotension, reduced cardiac output and
      liver hypoperfusion, ultimately leading to shock with a high mortality. There was
      a sequential and ordered activation of the coagulation, fibrinolytic and
      antifibrinolytic systems. GAS infusion induced a gradual, maximally 2.5-fold
      increase in plasma TAT levels. Plasma t-PA activity levels peaked at 2 h (nine
      fold increase), whereas the peak of PAI-1 activity was delayed (eight-fold
      increase at 4 h). These findings are similar to changes observed during endotoxin
      infusion. This procoagulant state favours disseminated intravascular coagulation
      and microthrombus formation, ultimately threatening tissue viability.

PMID- 10937805
TI  - Determination of activated protein C resistance in anticoagulated and lupus
      positive patients.
AB  - Clotting-based activated protein C (APC) assays have limitations when testing
      patients on oral anticoagulant (OA) therapy or with a lupus anticoagulant (LA).
      Predilution in factor V (FV)-deficient plasma and testing with phospholipid-rich
      Russell Viper venom (RVV)-based methods have been shown to be the most suitable
      methods when testing these patient groups, respectively. We evaluated a modified
      RVV based clotting test (Gradileiden V test; Gradipore, Sydney, Australia) in a
      large patient cohort and determined its sensitivity to the FV Leiden mutation. We
      also examined whether normal plasma can be used to dilute plasma from
      warfarinized patients without compromising sensitivity to the FV Leiden mutation.
      A total of 1,956 plasmas were studied including congenital protein C (five
      plasmas), and protein S deficiency (five plasmas), LA (29 plasmas), FV Leiden
      heterozygote (102 plasmas), and homozygote (five plasmas), warfarin (54 plasmas),
      standard heparin therapy (37 plasmas) and normal healthy controls (21 plasmas).
      Molecular analysis was performed on all samples. The effect of FV Leiden
      concentration on the APC ratio was examined by determining the APC resistance of
      a homozygous plasma serially diluted in six sources of normal plasma (NP). The
      relationship was non-linear and dependent on the initial APC ratio of the chosen
      source of NP. APC resistance was demonstrated in the varying sources of NP in
      dilutions of 1/4 (25% FV Leiden) to 1/32 (3% FV Leiden). A 1/2 dilution in pooled
      NP is recommended for patients on OA therapy because the test remains sensitive
      at levels of 25% FV Leiden and this is the dilution routinely used for other
      applications in a coagulation laboratory. The effect of a LA on the APC ratio was
      similarly studied by determining the APC resistance of a homozygous plasma
      serially diluted in two sources of LA-positive plasma. This relationship was also
      non-linear and dependent on the initial APC ratio of the LA-positive plasma. APC
      resistance was demonstrated in dilutions of 1/16 (6% FV Leiden) to 1/64 (1.5% FV
      Leiden) demonstrating the sensitivity of the test to APC resistance in the
      presence of a LA. Our results show the modified RVV-based test clearly predicts
      the presence of factor V Leiden in a large cohort of patients. The method offers
      advantages when testing patients with a LA and patients receiving warfarin
      providing a 1/2 predilution step in pooled NP is performed. Pooled NP does not
      affect the sensitivity of the test to the mutation, is routinely used in
      coagulation laboratories, and is considerably less expensive than FV-deficient
      plasma.

PMID- 10937806
TI  - Screening for abnormalities of the protein C anticoagulant pathway using the ProC
      Global assay. Results of a European multicenter evaluation.
AB  - ProC Global is a new global clotting assay designed to evaluate the functionality
      of the protein C anticoagulant pathway. It is based on the ability of endogenous
      activated protein C, generated by activation of protein C by Protac, to prolong
      an activated partial thromboplastin time, and the results are expressed in
      protein C activation time normalized ratio (PCAT-NR), after normalization. This
      multicenter trial involving five European laboratories was designed in order to
      determine the ability of the ProC Global assay to distinguish patients with and
      without abnormalities of the protein C pathway. The PCAT-NR was significantly
      lower in the patients with a thrombotic history not on oral anticoagulant
      treatment (n = 627) than in the healthy controls (n = 148), even after exclusion
      from both groups of the patients with abnormality of the protein C pathway. Using
      receiver operator characteristics analysis, the cut-off level of PCAT-NR = 0.80
      was found to provide the best sensitivity-specificity ratio. All the carriers of
      the factor V Leiden mutation (n = 73), as well as all the patients with activated
      protein C resistance (n = 42), had a PCAT-NR below 0.80. The ProC Global assay
      performed well in patients with combined defects (97.0%, n = 33) or protein C
      deficiency (91.3%, n = 46), but it failed to detect all of them, and one patient
      with combined defects as well as four patients with a low protein C level had a
      PCAT-NR above the cut-off level. The sensitivity of the assay for protein S
      deficiency (n = 58) was weak (only 69.0%) and, surprisingly, more than 40% of the
      375 patients without any of these abnormalities of the protein C pathway had a
      PCAT-NR below the cut-off level.

PMID- 10937807
TI  - Heparin-binding proteins are involved in thrombin time variability in normal and
      patient plasmas.
AB  - The ability of plasma proteins to neutralize the anticoagulant activity of
      heparin was studied using a thrombin time assay with 20 normal adult and 207
      patient plasma samples. The thrombin times of normal adult plasmas spiked with
      the same amount of heparin were found to vary significantly, and this variability
      was attributed to differences in heparin-binding proteins among individuals. This
      possibility was investigated by determining thrombin times for a variety of
      plasma samples following proteolytic digestion. A study of patient pooled plasma
      showed that incubation with a protease increased the thrombin time from 23 s to >
      300 s, suggesting that the anticoagulant activity of heparin could be neutralized
      by plasma proteins and released with proteolytic digestion. Incubation of the
      digested plasma with heparinase I returned the thrombin time almost to control
      values. In addition, patients who received prior heparin injections had different
      responses to similar dosages of heparin, as indicated by differences in thrombin
      times. Thus, the anticoagulant activity of heparin may be affected by the balance
      between free heparin and protein-bound heparin in plasma.

PMID- 10937808
TI  - Hemorrhagic fever virus-induced changes in hemostasis and vascular biology.
AB  - Viral hemorrhagic fever (VHF) denotes a virus-induced acute febrile, hemorrhagic
      disease reported from wide areas of the world. Hemorrhagic fever (HF) viruses are
      encapsulated, single-stranded RNA viruses that are associated with insect or
      rodent vectors whose interaction with humans defines the mode of disease
      transmission. There are 14 HF viruses, which belong to four viral families:
      Arenaviridae, Bunyaviridae, Filoviridae and Flaviviridae. This review presents,
      in order, the following aspects of VHF: (1) epidemiology, (2) anomalies of
      platelets and coagulation factors, (3) vasculopathy, (4) animal models of VHFs,
      (5) pathogenic mechanisms, and (6) treatment and future studies. HF viruses
      produce the manifestations of VHFs either by direct effects on cellular functions
      or by activation of immune and inflammatory pathways. In Lassa fever, Rift Valley
      fever and Crimean-Congo HF, the main feature of fatal illness appears to be
      impaired/delayed cellular immunity, which leads to unchecked viremia. However, in
      HF with renal syndrome and dengue HF, the immune response plays an active role in
      disease pathogenesis. The interplay of hemostasis, immune response, and
      inflammation is very complex. Molecular biologic techniques and the use of animal
      models have helped to unravel some of these interactions.

PMID- 10937809
TI  - Risk of venous thromboembolism associated with the insertion/deletion
      polymorphism in the angiotensin-converting enzyme gene.
AB  - The circulating levels of angiotensin I-converting enzyme (ACE) are linked with a
      287-base pair insertion/deletion (I/D) polymorphism at intron 16 of the ACE gene.
      Thus, the homozygous deletion (D/D genotype) could cause chronic
      vasoconstriction, arterial hypertension and, possibly, coronary artery disease.
      Also, the increase in plasminogen activator inhibitor-1 level and impaired
      fibrinolysis were related with the D/D genotype. The D allele has been recently
      associated with venous thrombosis among African-American men as well as among
      patients that underwent elective total hip replacement. We assess the risk of
      venous thromboembolism (VTE) linked with each genotype of the I/D ACE gene
      polymorphism in a Caucasian population by means of a case-control study. We
      genotyped the ACE gene in a series of 148 patients aged 45.0 +/- 16.0 years
      (range, 11-80 years), objectively diagnosed in our centre of deep-vein thrombosis
      or pulmonary embolism, and in 240 thrombosis-free subjects (25-75 years) from the
      same geographic area. The observed difference in D allele frequencies between
      patients (0.56) and controls (0.62) was nonsignificant overall; however,
      statistical significance (P = 0.05) was found by considering the recessive
      hypothesis (D/D versus I/ D + I/I) [odds ratio (OR) = 0.64, 95% confidence
      interval (CI95) = 0.42-0.99]. The OR was 0.88 (CI95 = 0.51-1.53; P = 0.65) for
      the dominant hypothesis (D/D + I/D versus I/I genotypes). The relative risk for
      the D allele was close to 1 for the dominant hypothesis, both considering gender
      and recurrent tendency; however, it was protective in men regarding the recessive
      hypothesis (OR = 0.53, CI95 = 0.29-0.97, P = 0.04). The I/D ACE allele
      distribution was similar among the 46 thrombophilic patients (antithrombin,
      protein C or protein S deficiencies, factor V R506Q, factor II G20210A or lupus
      anticoagulant). In conclusion, among (Spanish) Caucasians, this study does not
      support the hypothesis that the deletion allele (D) of the ACE gene could be a
      significant risk factor for VTE, being protective in men.

PMID- 10937810
TI  - Further evidence for the presence of anti-protein S autoantibodies in patients
      with systemic lupus erythematosus.
AB  - Acquired protein S (PS) deficiency in systemic lupus erythematosus (SLE) has been
      previously reported, but its mechanism and its possible thrombotic role have not
      been established. The aim of our study was to provide further evidence for auto
      immune PS deficiency in 27 Tunisian SLE patients, using PS-specific enzyme-linked
      immunosorbent assay (ELISA) and surface plasmon resonance technology (SPR). PS
      deficiencies for PS activity, free PS or total PS, respectively, were found in
      19, 18 and 12 patients. A significant correlation (r= -0.475, P< 0.016) was found
      between free/total PS ratio and C4bBP levels, suggesting a role of inflammation
      in free PS deficiency. Immunoglobulin IgG antibodies to PS were detected in four
      patients by both ELISA and SPR, in six patients only by ELISA, and in two
      patients only by SPR. Signals for anti-PS IgG by ELISA and SPR were, however,
      significantly correlated (r = 0.549, P = 0.003). These results suggest that an
      auto-immune mechanism could account for low PS activity in patients with SLE.
      Auto-antibodies to PS may form immune complexes, inducing increased clearance of
      PS or interfering with the protein C-protein S system.

PMID- 10937811
TI  - Prevalence of factor V Leiden and the G20210A prothrombin-gene mutation in
      inflammatory bowel disease.
AB  - A hypercoagulable state has been hypothesized as a contributing factor in the
      pathogenesis of inflammatory bowel disease (IBD); moreover, such patients have an
      increased risk of thrombotic complications. The aim of the present paper was to
      study the prevalence of the two most important causes of inherited thrombophilia:
      factor V Leiden and the G20210A prothrombin-gene mutation in patients with
      Crohn's disease (CD) and ulcerative colitis (UC). Fifty-two patients affected by
      IBD (33 UC and 19 CD, 16 female and 36 male; mean age, 42 years) and 156 healthy
      controls (48 female and 108 male; mean age, 37 years) were studied. Seven out of
      52 patients (13%) had previous thrombotic events. High molecular weight DNA was
      analysed for the presence of factor V Leiden and the G20210A prothrombin-gene
      mutation. One out of 52 IBD patients (1.9%) and three out of 156 control subjects
      (1.9%) were heterozygous for factor V Leiden. One IBD patient (1.9%) and four
      healthy controls (2.6%) were heterozygous for the prothrombin-gene mutation. The
      prevalence of the two mutations was similar in patients and controls. In the
      subgroup of IBD patients with previous thrombotic events, only one patient was
      heterozygous for the prothrombin-gene mutation. Factor V Leiden and the G20210A
      prothrombin-gene mutation do not seem to play a major role in the pathogenesis of
      IBD or be associated with an increased incidence of thrombotic complications, but
      with limited data.

PMID- 10937812
TI  - Treatment of epilepsy in the new millennium.
AB  - Treatment options for epilepsy have increased markedly since 1990, when only
      carbamazepine, phenytoin, phenobarbital, primidone, and valproate were used
      commonly for partial and secondarily generalized seizures. Those with primary
      generalized seizures received ethosuximide or valproate. Over the past decade,
      however, additional agents have been introduced, with the promise of improved
      seizure control and minimal side effects. The new antiepileptic drugs (AEDs)
      felbamate, gabapentin, lamotrigine, tiagabine, topiramate, vigabatrin and
      oxcarbazepine-have demonstrated superior efficacy for some with refractory
      epilepsy. In addition, the new agents frequently are better tolerated when used
      as monotherapy or adjunctive therapy. The optimal place for the new AED will
      require additional studies and careful postmarketing surveillance and
      assessments. Although these AEDs offer benefits, not all patients with epilepsy
      have responded. Thus, the search for new AEDs continues.

PMID- 10937813
TI  - Antiepileptic drug pharmacokinetics and interactions: impact on treatment of
      epilepsy.
AB  - An understanding of epilepsy therapy's pharmacokinetic and drug interaction
      principles-combined with knowledge of antiepileptic drug (AED) clinical
      pharmacology-allows more effective use of these drugs. The most desirable
      pharmacokinetic characteristic is a linear relationship between dose and steady
      state concentration, as this determines the ease or difficulty in determining the
      appropriate dose. Drug-drug interactions affecting AED metabolism are common,
      clinically important, and, until recently, often unpredictable. Advances in
      molecular biology have identified specific enzymes responsible for AED metabolism
      and interactions. Clinicians now can identify potential interactions and avoid or
      manage them by adjusting drug dosage. Most newer AEDs follow or approximate
      linear pharmacokinetics, are absorbed extensively and consistently, are not
      significantly bound to plasma proteins, do not form active metabolites, and have
      few, if any, drug interactions. In cases where interactions occur between newer
      AEDs and other drugs, knowledge of these interactions reduces the likelihood of
      serious adverse events. The pharmacokinetics of the newer AEDs simplify drug
      dosing and monitoring and should lead to improved patient care.

PMID- 10937814
TI  - Safety and efficacy of oxcarbazepine: results of randomized, double-blind trials.
AB  - Oxcarbazepine is approved as monotherapy and adjunctive therapy for partial
      seizures with and without secondarily generalized seizures in adults and as
      adjunctive therapy for partial-onset seizures in children aged 4-16 years. The
      clinical development of oxcarbazepine is different from the newer antiepileptic
      drugs (AEDs) in the extent and concordance of results across clinical trials. The
      safety and efficacy of oxcarbazepine was evaluated in adjunctive therapy trials,
      in comparative monotherapy trials with classic AEDs in adults and children with
      newly diagnosed epilepsy, in monotherapy therapeutic failure design trials in
      patients with refractory partial seizures, and in trigeminal neuralgia and
      affective disorder. The results of oxcarbazepine in treating epilepsy are
      discussed.

PMID- 10937815
TI  - Special considerations for women with epilepsy.
AB  - Women with epilepsy present health care providers with unique problems and
      opportunities for advancement of care. The fundamentals of epileptic
      pathophysiology are similar in both sexes. There are, however, some significant
      differences. Cosmetic effects of antiepileptic drugs (AEDs) may have different
      implications for women. Women who have seizures associated with their menstrual
      cycle may need special attention regarding their cyclic hormonal changes and AED
      selection. Antiepileptic drugs may reduce the effectiveness of hormonal
      contraception. Women with epilepsy have higher rates of infertility and an
      increased prevalence of reproductive and endocrine disorders. The majority of
      women with epilepsy have normal, healthy children, but their pregnancies are
      considered high risk due to an increase in seizure frequency, metabolic
      alterations of AEDs (which complicate management), and an increased risk of
      adverse pregnancy outcomes. These issues and an approach to optimize the
      management of women with epilepsy are discussed.

PMID- 10937816
TI  - Special considerations in treating children with epilepsy.
AB  - The incidence of seizures is high in infants and children. Many epileptic
      syndromes have their onset early in life. The increase in seizure susceptibility
      of the immature brain may be due to several factors, including an imbalance
      between excitatory and inhibitory processes, age-specific differences in ionic
      transport and clearance systems, high incidence of epileptogenic stimuli early in
      life, and the age-specific expression of pre- and perinatal brain anomalies. All
      of these factors must be taken into account when developing safe and effective
      age-specific antiepileptic drugs (AEDs). The use of developmental epilepsy
      models, followed by clinical trials in children, may help identify such AEDs.

PMID- 10937817
TI  - Management of seizures in the elderly.
AB  - The elderly are a substantial and rapidly increasing proportion of the
      population. They also have a high frequency of seizures, which can lead to
      serious consequences. The elderly differ from the young in that they may have
      many medical conditions, take numerous concomitant drugs, have different
      metabolic characteristics, and are more likely to suffer from neurologic
      conditions such as stroke. The elderly are also more sensitive to adverse effects
      of prescription drugs. As available antiepileptic drugs (AEDs) have roughly
      equivalent efficacy, side-effect profiles are a major determinant in charting
      therapy. The older AEDs have a well-known collection of undesirable side effects.
      Newer AEDs have potential advantages for the elderly, particularly with respect
      to tolerability. The characteristics of seizures in the elderly and guidelines
      for their treatment are discussed.

PMID- 10937818
TI  - Current discoveries on the cognitive effects of antiepileptic drugs.
AB  - The cognitive effects of antiepileptic drugs (AEDs) are of particular concern to
      clinicians because these drugs are the primary therapeutic modality for managing
      epilepsy. In general, the cognitive effects of most AEDs are modest and offset by
      their benefit in reducing seizures. Nonetheless, the cognitive effects of a
      particular AED may be clinically significant when treating specific patient
      populations, such as children and the elderly.

PMID- 10937819
TI  - Antiepileptic drug treatment: outcomes and adherence.
AB  - The goal in treating patients with epilepsy is a cost-effective approach to the
      elimination of seizures or a reduction in their number and frequency while
      avoiding drug interactions and side effects, so as to achieve the best possible
      quality of life. Among the desirable outcomes are an enhanced understanding of
      epilepsy by patients, caregivers, and society, and a lessening of the
      psychosocial risks of this disease. Patients fail to achieve their goals and
      outcomes when they fail to adhere to the drug regimen or when a less-than
      adequate drug regimen is prescribed. To help improve adherence, once- or twice
      daily formulations should be used. New antiepileptic drugs (AEDs) increase the
      possibility of effective treatment for a patient who initially fails therapy.
      Working together, patients and clinicians can maximize the effectiveness of AED
      therapy and the potential for achieving desired goals and outcomes.

PMID- 10937820
TI  - Dynamical analysis of gene networks requires both mRNA and protein expression
      information.
AB  - One of the important goals of biology is to understand the relationship between
      DNA sequence information and nonlinear cellular responses. This relationship is
      central to the ability to effectively engineer cellular phenotypes, pathways, and
      characteristics. Expression arrays for monitoring total gene expression based on
      mRNA can provide quantitative insight into which gene or genes are on or off; but
      this information is insufficient to fully predict dynamic biological phenomena.
      Using nonlinear stability analysis we show that a combination of gene expression
      information at the message level and at the protein level is required to describe
      even simple models of gene networks. To help illustrate the need for such
      information we consider a mechanistic model for circadian rhythmicity which shows
      agreement with experimental observations when protein and mRNA information are
      included and we propose a framework for acquiring and analyzing experimental and
      mathematically derived information about gene networks.

PMID- 10937821
TI  - Isotopomer analysis using GC-MS.
AB  - Knowledge of the complete isotopomer distribution represents the ultimate amount
      of information on the labeling pattern of a metabolite. One technique for
      measuring the isotopomer distributions is the analysis of the multiplet
      intensities arising from the 13C-13C couplings in NMR spectroscopy. While this
      technique has proven to be very valuable in the elucidation of labeling patterns
      of C2 and C3 units of various amino acids, fragments larger than C3 are very
      difficult to measure. Another technique, GC-MS, offers a unique possibility of
      analyzing fragments larger than C3 and GC-MS is therefore able to give
      information which is complementary to the information that can be obtained from
      NMR spectroscopy. In this work we have developed fast, simple, and robust GC-MS
      methods that can be used to gain information on the labeling patterns of the
      amino acids in a crude biomass hydrolysate. It is shown that a combination of
      information obtained from these analyses and information from the NMR
      spectroscopy is able to yield a much more complete picture of the isotopomer
      distributions of the amino acids than any of the two techniques alone. The GC-MS
      method was used for analyzing the labeling patterns of amino acids from a batch
      cultivation of Penicillium chrysogenum grown on fully labeled glucose. The data
      from this analysis showed no signs of any significant carbon isotope effects, and
      the measurements can therefore be used without corrections for metabolic flux
      analysis.

PMID- 10937822
TI  - Glucose/citrate cometabolism in Lactococcus lactis subsp. lactis biovar
      diacetylactis with impaired alpha-acetolactate decarboxylase.
AB  - The pyruvate metabolism of a Lactococcus lactis subsp. lactis biovar
      diacetylactis mutant deficient in alpha-acetolactate decarboxylase and its wild
      type strain was studied during batch cultivations. A chemically defined medium
      was used containing glucose as carbon- and energy-source. The alpha-acetolactate
      decarboxylase deficiency had no effect on the specific growth rate. Addition of
      citrate was found to increase the specific growth rate of both strains under
      aerobic and anaerobic conditions. The product formation was monitored throughout
      the cultivations. The carbon- and redox-balances were within the accuracy of the
      experimental data. When citrate was added, alpha-acetolactate, diacetyl, and
      acetoin were formed, and aeration was shown to have a positive effect on the
      formation of these metabolites. By omitting lipoic acid (required for a
      functional pyruvate dehydrogenase complex) from the growth medium, a similar
      stimulatory effect on alpha-acetolactate, diacetyl, and acetoin formation was
      observed under aerobic conditions. The strain with impaired alpha-acetolactate
      decarboxylase activity accumulated alpha-acetolactate which resulted in an
      increased diacetyl formation compared to the wild-type strain, under aerobic and
      anaerobic conditions.

PMID- 10937823
TI  - A maximum production strategy of lysine based on a simplified model derived from
      a metabolic reaction network.
AB  - The aim of this study is to develop a strategy for maximum production of a target
      product with a simplified model derived from a metabolic reaction network through
      an example of lysine production. Based on the model, a search for the optimal
      specific growth rate profile was conducted among the available conditions of
      batch fermentation based on the derived model, when the total fermentation time
      was fixed. The optimal specific growth rate was obtained as a boundary control:
      initially, the specific growth rate was maintained at a maximum value and was
      subsequently switched to a critical value giving the maximum specific production
      rate. To make the specific growth rate follow this optimal profile as accurately
      as possible in batch mode, first, an appropriate initial concentration of leucine
      was employed in the experiment. Second, the feeding strategy of leucine was
      further studied. The specific growth rate profile with feeding was closer to the
      optimal one and the amount of lysine produced at the final stage of fermentation
      was increased about twofold, compared to that in the batch fermentation. Finally,
      the strategy was summarized as an algorithm for general use of this method.

PMID- 10937824
TI  - In vivo 13C NMR study of the bidirectional reactions of the Wood-Werkman cycle
      and around the pyruvate node in Propionibacterium freudenreichii subsp. shermanii
      and Propionibacterium acidipropionici.
AB  - This study used in vitro 13C NMR spectroscopy to directly examine bidirectional
      reactions of the Wood-Werkman cycle involved in central carbon metabolic pathways
      of dairy propionibacteria during pyruvate catabolism. The flow of [2-13C]pyruvate
      label was monitored on living cell suspensions of Propionibacterium
      freudenreichii subsp. shermanii and Propionibacterium acidipropionici under
      acidic conditions. P. shermanii and P. acidipropionici cells consumed pyruvate at
      apparent initial rates of 161 and 39 micromol min(-1) g(-1) (cell dry weight),
      respectively. The bidirectionality of reactions in the first part of the Wood
      Werkman cycle was evident from the formation of intermediates such as [3
      13C]pyruvate and [3-13C]malate and of products like [2-13C]acetate from [2
      13C]pyruvate. For the first time alanine labeled on C2 and C3 and aspartate
      labeled on C2 and C3 were observed during [2-13C]pyruvate metabolism by
      propionibacteria. The kinetics of aspartate isotopic enrichment was evidence for
      its production from oxaloacetate via aspartate aminotransferase. Activities of a
      partial tricarboxylic acid pathway, acetate synthesis, succinate synthesis,
      gluconeogenesis, aspartate synthesis, and alanine synthesis pathways were evident
      from the experimental results.

PMID- 10937825
TI  - Dynamics of glucose uptake by single Escherichia coli cells.
AB  - The fluorescent glucose analog, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2
      deoxyglucose (2-NBDG), was used to measure rates of glucose uptake by single
      Escherichia coli cells. When cell populations were exposed to the glucose analog,
      2-NBDG was actively transported and accumulated in single cells to a steady-state
      level that depended upon its extracellular concentration, the glucose transport
      capacity of the cells, and the intracellular degradation rate. The dependence
      upon substrate concentration could be described according to Michaelis-Menten
      kinetics with apparent saturation constant KM = 1.75 microM, and maximum 2-NBDG
      uptake rate= 197 molecules/cell-second. Specificity of glucose transporters to
      the analog was confirmed by inhibition of uptake of 2-NBDG by D-glucose, 3-o
      methyl glucose, and D-glucosamine, and lack of inhibition by L-glucose.
      Inhibition of 2-NBDG uptake by D-glucose was competitive in nature. The assay for
      2-NBDG uptake is extremely sensitive such that the presence of even trace amounts
      of D-glucose in the culture medium (approximately 0.2 microM) is detectable. The
      rates of single-cell analog uptake were found to increase proportionally with
      cell size as measured by microscopy or single-cell light scattering intensity.
      The assay was used to identify and isolate mutant cells with altered glucose
      uptake characteristics. A mathematical model was developed to provide a
      theoretical basis for estimating single-cell glucose uptake rates from single
      cell 2-NBDG uptake rates. The assay provides a novel means of estimating the
      instantaneous rates of nutrient depletion in the growth environment during a
      batch cultivation.

PMID- 10937826
TI  - Importance of phosphoenolpyruvate carboxylase of Corynebacterium glutamicum
      during the temperature triggered glutamic acid fermentation.
AB  - To give clues about the respective importance of phosphoenol-pyruvate carboxylase
      (PEPc) and pyruvate carboxylase (Pc) in Corynebacterium glutamicum metabolism
      during a temperature triggered glutamic acid fermentation, PEPc activity was
      genetically amplified and Pc activity was suppressed by biotin limitation in the
      culture medium. In absence of Pc activity, glutamate production was dramatically
      reduced whereas lactate excretion was strongly increased. Whereas PEPc
      amplification in excess of biotin (4 mg/L) only slightly modified the cell
      kinetics, under biotin limiting conditions this amplification strongly improved
      the glutamate production (4 microg/L). When Pc was absent, PEPc activity was
      sufficient to allow up to 70% of the maximal glutamate production rate and seemed
      to have an important anaplerotic role, especially at the beginning of the
      production phase. In contrast, Pc was predominant during the remainder of the
      glutamate fermentation.

PMID- 10937827
TI  - Aged garlic extract suppresses lipid peroxidation induced by beta-amyloid in PC12
      cells.

PMID- 10937828
TI  - Is S-100 protein a suitable marker for adult Schwann cells?

PMID- 10937829
TI  - Development of a new serum-free cell culture system, McCoy-Plovdiv.

PMID- 10937830
TI  - Isoleucine prevents rat salivary gland epithelial cells from apoptosis in serum
      free culture.

PMID- 10937831
TI  - Primary culture of avian pancreatic acinar cells for heterologous gene
      expression.

PMID- 10937832
TI  - Efficient translocation and processing with Xenopus egg extracts of proteins
      synthesized in rabbit reticulocyte lysate.
AB  - Cell-free translation/translocation systems are broadly applied to examine gene
      expression and characterize the structure-function relationship of gene products.
      We present the characterization of Xenopus egg extract (XEE) translocation and
      processing of proteins synthesized in rabbit reticulocyte lysate. The XEE was
      prepared from eggs laid by adult female frogs that received serial injections of
      gonadotropins. The eggs were then dejellied in 2% L-cysteine-HCl and the
      cytoplasm extracted by centrifugation at 10,000 rpm for 15 min. The in vitro
      translocation and processing of XEE was examined with a cell-free translation
      system containing reticulocyte lysate, and appropriate messenger ribonucleic acid
      (RNA) or complementary deoxyribonucleic acid plasmids with RNA polymerase. Cell
      free production of the following proteins were used to assess posttranslational
      modifications: Escherichia coli beta-lactamase for signal sequence cleavage,
      Saccharomyces cerevisiae alpha-mating factor for translocation and N-linked
      glycosylation, the soluble protein luciferase for functional activity, and the
      membrane-bound human insulin receptor for translation efficiency. All translation
      products were identified by [35S]-methionine labeling, sodium dodecyl sulfate
      polyacrylamide gel electrophoresis and fluorography. The results demonstrate that
      (1) XEE produces near-complete signal sequence and N-glycosylation processing of
      proteins synthesized in reticulocyte lysate, (2) XEE contains endoplasmic
      reticulum-equivalent microsomes, which allows for protein translocation and
      protease protection, (3) the addition of XEE in the translation reaction does not
      affect synthesis and chemiluminescence activity of luciferase, (4) XEE is
      efficient in processing the nascent 160-kDa human insulin receptor precursor, a
      transmembrane protein, and (5) as compared to canine pancreatic microsomes, XEE
      translocation efficiency is minimally decreased with the addition of
      dimethylsulfoxide. These results are the first description of the combined use of
      XEE with reticulocyte lysate and clearly demonstrate a higher efficiency of
      translocation and processing compared to canine pancreatic microsomes. This
      method of cell-free translation and processing allows for more extensive in vitro
      examination of posttranslational modifications of secretory and membrane-bound
      proteins.

PMID- 10937833
TI  - Characterization of novel clonal murine endothelial cell lines with an extended
      life span.
AB  - A murine endothelial cell line was recently established from microvessels that
      had invaded a subcutaneous sponge implant (Dong, Q. G.; Bernasconi, S.;
      Lostaglio, S., et al. Arterioscl. Thromb. Vasc. Biol. 17:1599-1604; 1997). From
      these sponge-induced endothelial (SIE) cells, we have isolated two subpopulations
      endowed with different phenotypic properties. Clone SIE-F consists of large,
      highly spread cells that have a relatively slow growth rate, form contact
      inhibited monolayers, do not grow under anchorage-independent conditions, express
      elevated levels of thrombospondin-1 (TSP-1) and are not tumorigenic in vivo. In
      contrast, clone SIE-S2 consists of small, spindle-shaped cells that have a high
      proliferation rate, do not show contact-inhibition, grow under anchorage
      independent conditions, express very low levels of TSP-1 and are tumorigenic in
      vivo. Both clones express the endothelial markers vascular endothelial-cadherin
      and vascular intercellular adhesion molecule-1, but do not express CD31 and E
      selectin. In addition, SIE-S2 cells, but not SIE-F cells, express the alpha
      smooth muscle actin isoform. SIE-S2 cells, but not SIE-F cells, are able to form
      branching tubes in fibrin gels. The SIE-F and SIE-S2 clones, which have
      properties of nontransformed and transformed cells, respectively, should provide
      useful tools to investigate physiological and pathological processes involving
      vascular endothelium.

PMID- 10937835
TI  - 4-Hydroxytamoxifen-induced cytotoxicity and bisphenol A: competition for estrogen
      receptors in human breast cancer cell lines.
AB  - Increasing concerns over the effects of environmental estrogens on wildlife and
      humans have highlighted the need for screening systems to assess potentially
      estrogenic effects of test compounds. As a result, in vitro screening methods
      such as cell proliferation assays using the estrogen-responsive human breast
      cancer cell line, MCF-7, have been developed. The present study describes an
      alternative in vitro approach for the assessment of such xenoestrogens, based on
      estrogenic rescue of MCF-7 cells from antiestrogen-induced cytotoxicity. This
      method measures the ability of various estrogenic compounds to compete with a
      known estrogen-receptor-mediated antihormonal drug, 4-hydroxytamoxifen, using the
      1-[4,5-dimethylthiazol-2-yl]-3,5-diphenylformazan (MTT) assay to assess
      mitochondrial activity. Because 4-hydroxytamoxifen treatment of cells results in
      a dramatic decrease in mitochondrial dehydrogenase activity which is directly
      related to their estrogen-receptor content, inhibition of this effect with
      estrogenic compounds represents an estrogen-receptor interaction, or estrogenic
      rescue. The estrogenic compounds tested include a weak xenoestrogen, bisphenol A
      (BPA), and two biological estrogens, 17alpha- and 17beta-estradiol. Competitive
      inhibition of 4-hydroxytamoxifen-induced cytotoxicity by BPA was compared to that
      of the biological estrogens. The results indicate that the biological estrogens
      can successfully compete with the antiestrogen in a dose-dependent manner. In
      addition, the assay is sensitive enough to detect estrogenic rescue by even the
      very weak xenoestrogen, BPA, albeit at high BPA concentrations. This simple in
      vitro method could be used as an alternative or second-line screen for potential
      xenoestrogens.

PMID- 10937834
TI  - PIG3V, an immortalized human vitiligo melanocyte cell line, expresses dilated
      endoplasmic reticulum.
AB  - Vitiligo is an enigmatic pigmentary disorder of the skin. Factors potentially
      involved in the progressive loss of melanocytes from the basal layer of the
      epidermis include genetically determined aberrancies of the vitiligo melanocyte.
      It follows that analysis of melanocytes cultured from vitiligo donors can
      contribute to a further understanding of the etiopathomechanism. A setback for
      vitiligo research has been the limited availability of vitiligo-derived
      melanocytes. To overcome this limitation, we have generated a vitiligo melanocyte
      cell line according to a protocol established previously for the immortalization
      of normal human melanocytes. Vitiligo melanocytes Ma9308P4 were transfected with
      HPV16 E6 and E7 genes using the retroviral construct LXSN16E6E7. Successful
      transformants were selected using geneticin and subsequently cloned to ensure
      genetic homogeneity. The resulting cell line PIG3V has undergone more than 100
      cell population doublings since its establishment as a confluent primary culture,
      whereas untransfected melanocytes derived from adult skin senesce after a maximum
      of 50 population doublings. Cells immortalized by this transfection procedure
      retain lineage-specific characteristics and proliferate significantly faster than
      parental cells. In this study, the phenotype of PIG3V resembled melanocytes
      rather than melanoma cells in culture. Tyrosinase was processed properly and
      melanosomes remained pigmented. Importantly, ultrastructural characterization of
      PIG3V cells revealed dilated endoplasmic reticulum profiles characteristic of
      vitiligo melanocytes. An explanation for this dilation may be found in the
      retention of proteins with molecular weight of 37.5. 47.5, and 56.5 kDa, as
      determined by gel electrophoresis of microsomal proteins isolated from
      radiolabeled cells.

PMID- 10937836
TI  - Excitability and isometric contractile properties of mammalian skeletal muscle
      constructs engineered in vitro.
AB  - Our purpose was to engineer three-dimensional skeletal muscle tissue constructs
      from primary cultures of adult rat myogenic precursor cells, and to measure their
      excitability and isometric contractile properties. The constructs, termed
      myooids, were muscle-like in appearance, excitability, and contractile function.
      The myooids were 12 mm long and ranged in diameter from 0.1 to 1 mm. The myooids
      were engineered with synthetic tendons at each end to permit the measurement of
      isometric contractile properties. Within each myooid the myotubes and fibroblasts
      were supported by an extracellular matrix generated by the cells themselves, and
      did not require a preexisting scaffold to define the size, shape, and general
      mechanical properties of the resulting structure. Once formed, the myooids
      contracted spontaneously at approximately 1 Hz, with peak-to-peak force
      amplitudes ranging from 3 to 30 microN. When stimulated electrically the myooids
      contracted to produce force. The myooids (n = 14) had the following mean values:
      diameter of 0.49 mm, rheobase of 1.0 V/mm, chronaxie of 0.45 ms, twitch force of
      215 microN, maximum isometric force of 440 microN, resting baseline force of 181
      microN, and specific force of 2.9 kN/m2. The mean specific force was
      approximately 1% of the specific force generated by control adult rat muscle.
      Based on the functional data, the myotubes in the myooids appear to remain
      arrested in an early developmental state due to the absence of signals to promote
      expression of adult myosin isoforms.

PMID- 10937838
TI  - Salt intake and sensitivity of intestinal and renal Na+-K+ atpase to inhibition
      by dopamine in spontaneous hypertensive and Wistar-Kyoto rats.
AB  - The present study evaluated the activity of jejunal Na+-K+-ATPase and its
      sensitivity to inhibition by dopamine in spontaneous hypertensive rats (SHR) and
      Wistar-Kyoto (WKY) rats during low (LS), normal (NS) and high (HS) salt intake.
      Basal jejunal Na+-K+-ATPase activity in SHR on LS intake was higher than in WKY
      rats. Jejunal Na+-K+-ATPase activity in WKY rats, but not in SHR, on LS intake
      was significantly reduced (20% decrease) by dopamine (1 microM) and SKF 38393 (10
      nM), but not quinerolane (10 nM), this being antagonized the D1 receptor
      antagonist (SKF 83566). Changing from LS to NS or HS intake in WKY rats increased
      basal jejunal Na+-K+-ATPase activity and attenuated the inhibitory effect of
      dopamine. In SHR, changing from LS to NS or HS intake increased basal jejunal Na+
      K+-ATPase activity. Basal renal Na+-K+-ATPase activity in SHR on LS intake was
      similar to that in WKY rats and was insensitive to inhibition by dopamine.
      Changing from LS to NS or HS intake in WKY rats increased basal renal Na+-K+
      ATPase activity without affecting the inhibitory effect of dopamine. In SHR,
      changing from LS to NS or HS intake failed to alter basal renal Na+-K+-ATPase
      activity. It is concluded that inhibition of jejunal Na+-K+ ATPase activity by D1
      dopamine receptor activation is dependent on salt intake in WKY rats, and SHR
      animals fail to respond to dopamine, irrespective of their salt intake.

PMID- 10937837
TI  - Type IV collagen modulates angiogenesis and neovessel survival in the rat aorta
      model.
AB  - Type IV collagen is a major basement membrane component that has been implicated
      in the regulation of angiogenesis. The purpose of this study was to evaluate the
      effect of type IV collagen on the angiogenic response of native endothelial cells
      in three-dimensional vascular organ culture. Rings of rat aorta were cultured
      under serum-free conditions in gels of type I collagen with or without type IV
      collagen. In the absence of type IV collagen, aortic rings generated neovessels,
      which proliferated until day 9 and gradually regressed during the second and
      third weeks of culture. Type IV collagen promoted neovessel elongation and
      survival in a dose-dependent manner. Microvascular length increased by 43, 57,
      and 119% over control values in cultures treated with 3, 30, and 300 microg/ml
      type IV collagen, respectively. When used at high concentrations (300 microg/ml)
      type IV collagen stabilized the neovascular outgrowths and prevented vascular
      regression. Type IV collagen also promoted the formation of neovessels, but
      significant stimulatory effects were observed only at an intermediate
      concentration (30 microg/ml) and were no longer significant at the high
      concentration (300 microg/ml). The observation that type IV collagen has dose
      dependent effects on vascular elongation, proliferation, and stabilization,
      supports the concept that the developing basement membrane of neovessels acts as
      a solid-phase regulator of angiogenesis, whose function varies depending on the
      concentration of its molecular components.

PMID- 10937839
TI  - Differences in time-related cardiopulmonary responses to hypoxia in three rat
      strains.
AB  - The cardiopulmonary profile of three rat strains (Sprague-Dawley, Wistar and High
      altitude-sensitive) was compared upon exposure to hypoxia (9% O2) for 0, 7 or 14
      days. No differences were observed among the in vitro contractile (ET-1) and
      relaxant (carbachol) responses of pulmonary artery isolated from the three
      strains during normoxia. Chronic hypoxia decreased ET-1 contractile responses and
      diminished relaxant responses to carbachol similarly in all strains. In Sprague
      Dawley, Wistar and High altitude-sensitive rats, pulmonary arterial pressure rose
      time-dependently and was elevated by 108%, 116% and 167%, respectively, after 14
      days of hypoxia compared to normoxic controls. Right ventricular hypertrophy was
      increased by 51%, 93% and 55%, respectively, at 14 days. Hypoxia-induced
      hypertrophy and medial thickening in the pulmonary vasculature were more
      pronounced in High altitude-sensitive rats. Sprague-Dawley exhibited hypoxia
      induced airway hyperresponsiveness to intravenous methacholine, but there were no
      hypoxia- or strain-related differences in in vitro tracheal contractility.
      Although each strain exhibited greater sensitivity for a particular hypoxia
      induced parameter, pulmonary vascular functional and structural changes suggest
      that High altitude-sensitive rats represent a choice model of hypoxia-induced
      pulmonary hypertension.

PMID- 10937840
TI  - The effects of monotherapy or combined therapy with an angiotensin converting
      enzyme inhibitor following initial treatment with calcium channel blockers on
      residual cardiovascular abnormalities.
AB  - The effects of sequential therapy with angiotensin-converting enzyme inhibitor
      (cilazapril) on left ventricular (LV) mass, LV diastolic function, and carotid
      artery distensibility were evaluated in 90 hypertensive patients whose blood
      pressure controlled below 140/90 mmHg with a calcium channel blocker monotherapy.
      The possibility of predicting the efficacy of cilazapril based on evaluation of
      biochemical and genetic markers of the renin-angiotensin system was examined.
      Before cilazapril therapy, LV diastolic function and carotid artery
      distensibility were significantly impaired in 32 patients with residual LV
      hypertrophy compared with patients without LV hypertrophy. Cilazapril improved
      the LV mass in these patients with LV hypertrophy and improved LV diastolic
      function in a subset of 20 patients with elevated plasma renin activity. Patients
      with residual LV hypertrophy accompanied by cardiovascular functional
      abnormalities. Subsequent treatment with cilazapril significantly improved LV
      morphology and function in those with residual LV hypertrophy or elevated plasma
      renin activity.

PMID- 10937841
TI  - Chronic blockade of hippocampal kappa receptors increases arterial pressure in
      conscious spontaneously hypertensive rats but not in normotensive Wistar Kyoto
      rats.
AB  - Previous studies in this laboratory have shown that dynorphins acting on
      hippocampal kappa opioid receptors in rat brain exert a restraining influence on
      arterial blood pressure and that a relative deficiency of their production in the
      spontaneously hypertensive rat (SHR) may be involved in SHR hypertension. Kappa
      receptor blockade should therefore exacerbate hypertension in SHR. We explored
      the latter possibility by chronic unilateral infusion of nor-binaltorphimine
      dihydrochloride (nor-BNI), a selective kappa receptor antagonist, into the right
      dorsal hippocampus of conscious SHR and normotensive Wistar-Kyoto (WKY) controls
      over a 14 day period. Additional controls consisted of similar hippocampal
      infusions of equivalent volumes of drug vehicle in both rat strains. Mean
      arterial pressure (MAP) and heart rates (HR) were determined in each animal once
      daily by the tail cuff method during this period. Nor-BNI induced a sustained
      increase in the basal high level of MAP in SHR from 132 +/- 8 to 150 +/- 10 mmHg
      throughout the 14 days and an increased HR from 427 +/- 17 to 477 +/- 30 on day 3
      to 5 following the drug. By contrast, nor-BNI had no significant effects on
      either MAP or HR in WKY rats and control infusions of drug vehicle were similarly
      without effect in both strains. The results support our previous suggestion that
      the kappa opioid system of the hippocampus ordinarily restrains arterial blood
      pressure in SHR since prolonged hippocampal kappa receptor blockade results in
      augmented hypertension in this strain.

PMID- 10937842
TI  - Influence of the timing of initiating antihypertensive therapy in hypertensive
      rats with renal failure.
AB  - The important contribution of hypertension to the progression of renal failure is
      well realized. However, it have been less discussed which drugs are suitable for
      the different stages of progressive renal failure. The present study examined the
      effects of timing of antihypertensive therapy using calcium channel blocker and
      angiotensin converting enzyme inhibitor in 5/6 nephrectomized spontaneously
      hypertensive rats (SHRs). Forty male 6 week old SHRs were divided into 5 groups
      (n=8 in each group), and they were placed on a high salt diet after 5/6
      nephrectomy. Group 1, high salt diet without any drug. Group 2 received 0.2
      mg/kg/day of amlodipine and group 3 received 0.2 mg/kg/day of enalapril mixed in
      the high salt diet from week 6 respectively. Similarly group 4 received the same
      doses of amlodipine, and group 5 received the same doses of enalapril from week
      10. Each drug protected from increasing blood pressure in 4 groups, and no
      significant difference was observed between the effects of amlodipine and
      enalapril. Proteinuria was reduced with both drugs. In histopathological
      evaluation, glomerulosclerosis was controlled only in group 2, and
      arterio/olosclerosis was significantly suppressed in all treated groups except
      group 5. From these results, both amlodipine and enalapril are renal protective
      in early stage of renal failure with hypertension. However, in advanced stage of
      renal failure, amlodipine is superior in its renal protective effect.

PMID- 10937843
TI  - Increased expression and shuttling of aquaporin-2 water channels in the kidney in
      DOCA-salt hypertensive rats.
AB  - An altered role of AQP2 water channels in DOCA-salt hypertension was
      investigated. DOCA-salt hypertension was induced in rats. Control groups were
      either treated with DOCA alone or subjected to a high-salt intake without DOCA.
      Four weeks after inducing the hypertension, AQP2 expression and shuttling were
      determined in the kidney. Adenylate cyclase activity was also determined to
      examine the upstream affecting the AQP2 system. The AVP-evoked cAMP generation in
      the cortex and outer medulla was augmented following the treatment with DOCA
      either alone or combined with high-salt intake. Accordingly, the expression and
      shuttling of AQP2 proteins were increased in the cortex and outer medulla. These
      findings suggest that DOCA enhances cAMP generation and expression/shuttling of
      AQP2 water channels in the kidney, which may be causally related with the
      development of hypertension.

PMID- 10937844
TI  - Role of endothelium and vasoconstrictor prostanoids in norepinephrine-induced
      vasoconstriction in isolated rat common carotid arteries.
AB  - We investigated the role of endothelium and vasoconstrictor prostanoids in the
      norepinephrine (NE)-induced vasoconstriction of isolated rat common carotid
      arteries (CCAs). Isolated CCAs were cannulated with stainless steel cannulae by
      the cannula inserting method. NE was administered intra- or extraluminally by a
      single microinjection. For denudation of endothelium, the intimal surface was
      gently rubbed with a cotton pellet. NE produced dose-related vasoconstricting
      responses in isolated arteries with intact endothelium. These responses were
      attenuated by pretreatment with denudation, OKY046, a thromboxane A2 synthesis
      inhibitor or indomethacin. The residual responses after denudation were further
      blocked by OKY046 or indomethacin. All NE-induced responses were blocked by a
      single injection of prazosin. There were no significant differences in responses
      between intra- and extraluminal administration of NE. These results show that
      most vasoconstriction induced by NE via alpha1-adrenoceptors in CCAs is dependent
      on vasoconstrictor prostanoids distributed both in endothelium and vascular
      smooth muscle.

PMID- 10937846
TI  - Ischemic retinitis as a result of acute episodic blood loss.
AB  - Acute episodic blood loss leads to a sudden change in the haemodynamics leading
      to a number of ocular and systemic effects. Occurrence of ischemic retinitis
      secondary to acute blood loss is of a very rare occurrence. This communication
      presents a case of infarction of the nerve fibre layer secondary to acute blood
      loss in a 55-year-old male.

PMID- 10937845
TI  - Ocular involvement in primary antiphospholipid syndrome. Ocular involvement in
      primary APS.
AB  - The purpose of this study is to evaluate the ocular findings in patients with the
      primary antiphospholipid syndrome (APS). PATIENTS AND METHODS: Twenty-two
      patients (44 eyes) with primary APS (17 women, 5 men) were examined. All patients
      were younger than 50 years (median age; 37.5 years). In 18 patients, fundus
      flourescein angiography was performed in addition to the ophthalmologic
      examination. RESULTS: Sixteen patients (72.7%) described visual symptoms.
      Anterior segment was normal in 19 patients (86.4%). Posterior segment
      abnormalities were observed in 15 patients (68.2%). Venous dilatation and
      tortuosity were the most common ocular findings. Retinal vascular occlusive
      disease was detected in 5 patients (22.7%). Flourescein angiography abnormalities
      were noted in 14 of the 18 patients (77.8%). The most common angiographic finding
      was pigment epithelial window defects. CONCLUSIONS: Our results indicate that
      posterior eye segment involvement is relatively common in the primary APS. It
      also seems that the screening for APS is important in young patients with retinal
      vascular occlusion, especially in those without conventional risk factors.

PMID- 10937847
TI  - High-pressure paint gun injury to the orbit and ocular adnexa.
AB  - High-pressure injection injury to the orbit and adnexa is a rare but potentially
      blinding type of trauma. Few cases of such injury have been reported in the
      literature. A 27-year-old Indian man accidentally injected paint material from a
      high-pressure nozzle gun into his left eye. Radiological investigation revealed
      the presence of paint material in the orbital tissues and the ethmoidal sinuses.
      The patient underwent two orbital surgeries to remove the paint material. He
      later developed signs suggestive of limbal stem cell failure and was treated with
      limbal stem cell autografting. He also has ophthalmoplegia with a compensatory
      anomalous head posture that was managed conservatively. We report the clinical
      course and outcome of this unfortunate patient to highlight the complexity of
      such an injury and the need for a multidisciplinary approach in its management.

PMID- 10937848
TI  - Subconjunctival cyst extending into the orbit.
AB  - A fourteen year old girl who had developed a large subconjunctival mass extending
      into the orbit is presented. The mass had appeared after a strabismus operation,
      and it caused a consecutive exotropia and decreased adduction in the affected
      eye. She had had this cyst for six years. A cranial CT scan confirmed the
      presence of a massive orbital cyst. This cyst was removed surgically.
      Postoperatively, exotropia and adduction limitation improved. The pathological
      report stated that it was an epithelial cyst. This cyst and its differential
      diagnosis is the subject of this paper.

PMID- 10937850
TI  - Occurrence of cholinergic nerve fibers in the human uveoscleral tissue.
AB  - We have studied the cholinergic nerve fibers (CNF) of human uveoscleral tissue in
      normal and pathological conditions (intraocular pressure: (IOP) of various
      degrees ) and have performed a quantitative image analysis of CNF with the aim of
      studying an hypothetical association between IOP and the uveoscleral level of
      cholinergic neurotransmitter in nerve fiber of the enucleated human eyes. Eleven
      patients, previously enrolled in our medical protocols are affected by an
      increase of IOP of various degrees, were subjected to surgical enucleation of one
      eyeball for traumatic or neoplastic reasons and were the donors of samples of the
      uveoscleral tissue for CNF demonstration. The samples were also submitted to
      quantitative image analysis. An enzymatic activity, Acetylcholinesterase (AChe),
      is present in nerve fibers that innervate the human uveoscleral tissue. The AChe
      positive nerve fibers represent about 7.2% of the observed area in normal
      conditions, while in patients with elevated IOP AChe activity is about 20.3% of
      the total observed area. The increase of AChe activity in our experiments, all
      performed under the same conditions, and therefore, with comparable results, may
      be related with the increase of IOP.

PMID- 10937849
TI  - Retinopathy following measles, mumps, and rubella vaccination in an immuno
      incompetent girl.
AB  - We describe a 4-year-old girl with subnormal visual acuity due to a bilateral
      retinopathy. The child had a history of encephalitis following MMR vaccination.
      Temporary retinopathy associated with measles, mumps, and rubella (MMR)
      vaccination has been described. Recently an idiopathic CD4+ T lymphocytopenia in
      the child was diagnosed. This cellular immunodeficiency supports our hypothesis
      of measles retinopathy after vaccination of an immuno-deficient child.

PMID- 10937851
TI  - Ferrous intraocular foreign bodies retained in the posterior segment: management
      options and results.
AB  - PURPOSE: Analysis of traditional versus comprehensive management techniques for
      eyes with ferrous IOFBs in the posterior segment. PATIENTS AND METHODS:
      Retrospective review of 30 eyes undergoing IOFB removal by EM and of 34 eyes
      managed by PPV techniques. RESULTS: Vitreous hemorrhage occurred commonly (EM
      group: 40%, PPV group: 50%). Only in the EM group did the intervention cause
      iatrogenic vitreous hemorrhage (23%) and has postextraction endophthalmitis
      developed (10%). Vision improved in 23% of eyes, deteriorated in 53%; >0.5 vision
      was achieved in 20%. Five EM eyes (17%) were anatomically lost; PVR developed in
      48% of the remaining eyes. In the PPV group, no eye was anatomically lost and PVR
      developed in 12%. Vision improved in 68% of eyes, deteriorated in 15%; >0.5
      vision was achieved in 68%. A single retinal impact site occurred in 71%, < or =2
      impact sites in 21% of eyes. CONCLUSIONS: Approximately one of two eyes with
      posterior segment IOFB develops vitreous hemorrhage, over two-thirds sustain at
      least one retinal lesion, and one-fifth of eyes suffer multiple retinal injuries.
      Both the anatomical (p = 0, 003) and the functional (p = 0, 005) prognoses are
      significantly better in eyes undergoing PPV compared to eyes with EM use. Timely
      PPV appears to markedly reduce the risk of endophthalmitis development. These
      results confirm the need to abandon the EM and perform PPV for eyes with
      posterior segment IOFBs.

PMID- 10937852
TI  - Clinical outcomes and costs of cataract surgery performed by planned ECCE and
      phacoemulsification.
AB  - PURPOSE: To compare clinical outcomes and costs of cataract surgery between
      patients operated with standard extracapsular extraction (ECCE) and those
      undergoing phacoemulsification. SETTING: Patients from the Ophthalmology
      Department of a teaching hospital in Barcelona (Spain) scheduled for cataract
      surgery, not combined with any other ophthalmic procedure. METHODS: A
      retrospective analysis has been performed on a database of 1046 patients
      undergoing ECCE and phacoemulsification. The outcome measures used were: surgical
      complications, visual acuity and costs of surgery and of follow-up. Overall rate
      of all complications and postoperative visual acuity were compared between the
      two groups, adjusting for age, preoperative visual acuity, medical and ocular
      comorbidity. RESULTS: 31.9% of the patients (334) underwent phacoemulsification,
      and 68.1% (712) underwent ECCE. Patients undergoing phacoemulsification presented
      a frequency of intra- and postoperative complications lower than those undergoing
      ECCE (odds ratio 0.57, 95%CI 0.37-0.87 and 0.66, 95%CI 0.46-0.96, respectively),
      specifically for intraoperative iris trauma (3.1% vs 0.3%, p = 0.004), residual
      posterior capsular opacity (2% vs 0.3%, p = 0.035) and postoperative corneal
      edema (7.4% vs 3.6%, p = 0.016). Costs of intervention and follow-up were lower
      for phacoemulsification compared with ECCE (23.9% and 14%, respectively). But
      global costs were slightly higher for phacoemulsification (4.87%), due to supply
      costs, which were more than twice those of ECCE. CONCLUSIONS:
      Phacoemulsification, when performed by an experienced surgeon, has better
      clinical outcomes than planned extracapsular extraction, and costs may be lower
      since supply costs are expected to decrease as the phacoemulsification technique
      becomes more widespread.

PMID- 10937854
TI  - Effects of perfluorophenanthrene on the human corneal endothelium.
AB  - PURPOSE: To evaluate long term effects of perfluorophenanthrene (C12F24), a
      perfluorocarbon fluid, in the anterior chamber of the human eye, where residual
      perfluorophenanthrene was retained in the eye postoperatively. METHODS: Slit-lamp
      microscopic and specular microscopic examinations of 4 eyes of 4 patients were
      performed. All the eyes were operated for complicated retinal detachment and they
      were aphakic at the end of the operations. Mean follow-up period was 10 months (6
      16 months). RESULTS: Perfluorophenanthrene was seen in the anterior chamber in
      the first or second day postoperatively as a single drop. In the third week,
      postoperatively, the first signs of splitting the perfluorophenanthrene (fish
      egging phenomena) was observed. There was no sign of corneal or anterior segment
      toxicity with the slit lamp microscopic examinations and the intraocular pressure
      was within normal limits during the follow-up period in all eyes. However, some
      structural changes of the corneal endothelium were shown by specular microscopy.
      Decreased endothelial cell density, a reversed illumination pattern in which the
      normally dark cellular boundaries appear bright and intracytoplasmic light
      reflecting bodies were signs of cellular damage at the contact sites whereas no
      significant changes were seen at non contact sites. CONCLUSION: Residual
      perfluorophenanthrene in the anterior chamber does not induce gross corneal
      damage or ocular inflammation, although structural changes indicating the damage
      of the corneal endothelium, can be shown by specular microscopy at the contact
      sites. Corneal endothelial changes seem to arise from a contact-dependent effect
      of the perfluorophenanthrene.

PMID- 10937853
TI  - Retinal detachment after posterior segment intraocular foreign body injuries.
AB  - PURPOSE: To identify the risk factors for retinal detachment after posterior
      segment intraocular foreign body (IOFB) injuries and to study the association
      between the development of retinal detachment and visual outcome. METHODS: Ninety
      six consecutive patients with posterior segment IOFB injuries were
      retrospectively reviewed. Vitrectomy techniques were used in primary and
      secondary treatment. Two eyes were eviscerated after primary repair because of
      Clostridium perfringens endophthalmitis. Factors analyzed included (1) entrance
      wound location, (2) presence of uveal prolapse, (3) presence of vitreous
      prolapse, (4) presence of traumatized iris, (5) presence of endophthalmitis, (6)
      location of IOFB, (7) size of IOFB, (8) use of scleral buckling and/or an
      encircling band, (9) use of gas tamponade, (10) use of lensectomy. Data were
      analyzed using univariate and multivariate logistic regression analysis. RESULTS:
      Retinal detachment was present in 6 eyes at presentation and occurred in another
      19 eyes after vitrectomy. After a mean follow-up of 8.6 months, 63 (65.6%) eyes
      achieved visual acuities of 20/200 or better, and total retinal detachment
      complicated by inoperable proliferative vitreoretinopathy was present in 9 (9.4%)
      eyes. Multivariate analysis identified retinal detachment as a factor
      significantly associated with a poor visual outcome (odds ratio = 4.54, 95%
      confidence interval [CI] = 1.05-19.6). Foreign body size of more than 4 mm (odds
      ratio = 5.8, 95% CI = 1.66-2.03) and presence of endophthalmitis (odds ratio =
      11.7, 95% CI = 2.57-52.9) were identified as the only predictive factors for the
      development of retinal detachment after vitrectomy. Use of prophylactic scleral
      buckling and/or an encircling band reduced the risk of developing postoperative
      retinal detachment. CONCLUSIONS: Retinal detachment after posterior segment IOFB
      injuries is associated with a poor visual outcome. Large IOFB and presence of
      endophthalmitis are the strongest predictive factors for the development of
      retinal detachment.

PMID- 10937855
TI  - Playing with the sarcoplasmic reticulum with Giovanni.

PMID- 10937856
TI  - Functional roles of dystrophin and of associated proteins. New insights for the
      sarcoglycans.
AB  - The discovery of the dystrophin gene, whose mutations lead to Duchenne's and
      Becker's muscular dystrophy (DMD and BMD), represents the first important
      landmark by which, in the last ten years, molecular biology and genetic studies
      have revealed many of the molecular defects of the major muscular dystrophies.
      Very rapidly, several studies revealed the presence at skeletal and cardiac
      muscle sarcolemma of a group of proteins associated to dystrophin. This includes
      a set of five transmembrane glycoproteins, the sarcoglycans, whose physiological
      role, however, is still poorly understood. Dystrophin and the associated proteins
      are believed to play an important role in membrane stability and maintenance
      during muscle contraction and relaxation. However, the absence of sarcoglycans
      from sarcolemma does not appear to affect membrane integrity suggesting that
      these components of the dystrophin complex are recipients of other important
      functions. This review deals with recent advances in the knowledge of sarcoglycan
      function and organization that may give important insights into the pathogenetic
      mechanisms of muscular dystrophies.

PMID- 10937857
TI  - Myopathies, cardiomyopathies, and heart transplantation: a tribute to Giovanni
      Salviati.

PMID- 10937858
TI  - Exercise intolerance and the mitochondrial respiratory chain.
AB  - The syndrome of exercise intolerance, cramps, and myoglobinuria is a common
      presentation of metabolic myopathies and has been associated with several
      specific inborn errors of glycogen or lipid metabolism. As disorders in fuel
      utilization presumably impair muscle energy production, it was more than a little
      surprising that exercise intolerance and myoglobinuria had not been associated
      with defects in the mitochondrial respiratory chain, the terminal energy-yielding
      pathway. Recently, however, specific defects in complex I, complex III, and
      complex IV have been identified in patients with severe exercise intolerance with
      or without myoglobinuria. All patients were sporadic cases and all harbored
      mutations in protein-coding genes of muscle mtDNA, suggesting that these were
      somatic mutations not affecting the germ-line. Another respiratory chain defect,
      primary coenzyme Q10 (CoQ10) deficiency, also causes exercise intolerance and
      recurrent myoglobinuria, usually in conjunction with brain symptoms, such as
      seizures or cerebellar ataxia. Primary CoQ10 deficiency is probably due to
      mutations in nuclear gene(s) encoding enzymes involved in CoQ10 biosynthesis.

PMID- 10937859
TI  - Mitochondria in muscle cell death.
AB  - Mitochondria, the main source of energy for eukaryotic cells through oxidative
      phosphorylation, also play a key role in the pathways to cell death. The mode of
      cell death may be influenced by the availability of ATP, and its very occurrence
      may critically depend on release of mitochondrial proteins like cytochrome c,
      apoptosis-inducing factor and possibly caspases 3 and 9. Ca2+-dependent onset of
      the permeability transition, caused by opening of a cyclosporin A-sensitive pore
      modulated by cyclophilin D, may play a major role in cell death through ATP
      depletion, disruption of Ca2+ homeostasis, and release of specific mitochondrial
      proteins. Dysregulation of Ca2+ homeostasis, proteolysis and a decreased ability
      to cope with oxidative stress are involved in the pathogenesis of Duchenne's
      muscular dystrophy downstream of the genetic lesion, and mitochondria appear as
      likely targets that may amplify the initial insult resulting in the irreversible
      events leading to cell demise. My colleagues and I are studying the permeability
      transition in skeletal muscle mitochondria, and we are validating bupivacaine in
      a short-term model of muscle cell toxicity involving mitochondrial depolarization
      and pore opening as early events. Specific goals for the future are to further
      define the role of mitochondria in muscle cell death, with particular emphasis on
      the role of the permeability transition pore and cyclophilin D, and to develop
      and test drugs able to affect its course in model systems in vitro and in the mdx
      mouse, an animal model of Duchenne's muscular dystrophy.

PMID- 10937860
TI  - Nuclear gene defects in mitochondrial disorders.
AB  - An increasing number of nuclear genes have been associated with abnormalities of
      oxidative phosphorylation and mitochondrial disorders. The protein products of
      these genes can be grouped into three categories: structural components of the
      respiratory chain, factors influencing the structural integrity or the copy
      number of mitochondrial DNA, and proteins which control the formation, assembly
      and turnover of the respiratory complexes. Loss-of-function mutations in SURF-1,
      a gene belonging to the third category, have been associated with Leigh syndrome
      with cytochrome c oxidase deficiency. Mature Surf-1 protein (Surf-1p) is a 30 kDa
      hydrophobic polypeptide whose function is still unknown. Using antibodies against
      human Surf-1p, we demonstrated that this protein is imported into mitochondria as
      a larger precursor. The same analysis revealed that no protein is present in cell
      lines harboring loss-of-function mutations of SURF-1, regardless of their type
      and position. We also generated several constructs with truncated or partially
      deleted SURF-1 cDNAs. None of these constructs, expressed into SURF-1 null mutant
      cells, were able to rescue the COX phenotype, suggesting that different regions
      of the protein are all essential for function. Finally, experiments based on 2D
      gel electrophoresis indicated that assembly of COX in SURF-1 null mutants is
      blocked at an early step, most likely before the incorporation of subunit II in
      the nascent intermediates composed of subunit I alone or subunit I plus subunit
      IV.

PMID- 10937861
TI  - How is muscle phenotype controlled by nerve activity?
AB  - Motor neurons are known to affect muscle growth and fiber type profile
      (fast/slow, oxidative/glycolytic) by regulating muscle gene expression. However,
      the mechanism by which the information contained in specific action potential
      patterns is decoded by the transcriptional machinery of muscle fiber nuclei
      remains to be established. This is a basic issue in nerve/muscle biology, which
      has major implications in neurology, sport medicine and aging. We describe here a
      general strategy aimed at identifying the signal transduction pathways mediating
      the effects of nerve activity. This approach is based on the overexpression of
      constitutively active or dominant negative transduction factors in regenerating
      skeletal muscle.

PMID- 10937862
TI  - Regulation of human muscle contraction at the cellular and molecular levels.
AB  - The rat is the most extensively characterized species with regard to regulation
      of muscle contraction and myofibrillar protein isoform expression, but there is
      reason to question whether results from small mammals, such as the rat, can be
      extrapolated directly to larger mammals, such as man. Studies of human muscle
      contraction have primarily used different in vivo muscle function measurements,
      i.e. measurements of force at different speeds of movement during electrical
      stimulation or voluntary activation. These measurements give important
      information on overall muscle function, but they are of limited value for our
      understanding of regulation of muscle contraction. In basic science, cellular-
      and molecular-physiological methods have been used for many years, but these
      techniques have so far only rarely been used in studies of human muscle
      contraction. Detailed studies of human muscle contraction can be performed in the
      short muscle fibre segments obtained by the percutaneous muscle biopsy technique
      both at the cellular and molecular level. The skinned fibre preparation in
      combination with a novel in vitro motility assay offers a unique possibility to
      investigate regulation of human muscle contraction at the cellular and molecular
      levels in the same muscle cell segment in both health and disease, i.e. in muscle
      cells characterized according to the type and amount of expressed myofibrillar
      protein isoforms.

PMID- 10937863
TI  - The role of sphingolipids in the control of skeletal muscle function: a review.
AB  - In this review, potential roles for the endogenous sphingolipid, sphingosine, and
      its derivatives are described for muscle cells. Sphingosine modulates the
      function of important calcium channels in muscle, including the ryanodine
      receptor (RyR) calcium release channel of the sarcoplasmic reticulum (SR).
      Sphingosine blocks calcium release through the SR ryanodine receptor and reduces
      the activity of single skeletal muscle RyR channels reconstituted into planar
      lipid bilayers. Sphingosine-blocked calcium release is coincident with the
      inhibitory effects of sphingosine on [3H]ryanodine binding to the RyR. The
      sphingomyelin signal transduction pathway has also been identified in both
      skeletal and cardiac muscle. A neutral form of sphingomyelinase (nSMase) enzyme
      has been localized to the junctional transverse tubule membrane. The high
      turnover of the SMase is responsible for the production of ceramide and
      sphingosine. HPLC analyses indicate that significant resting levels of
      sphingosine are present in muscle tissue. A model of excitation-contraction
      coupling is presented suggesting a potential role for this endogenous
      sphingolipid in normal muscle function. Putative roles for sphingolipid mediators
      in skeletal muscle dysfunction are also discussed. We hypothesize that
      sphingosine plays important roles in malignant hyperthermia and during the
      development of muscle fatigue.

PMID- 10937864
TI  - Volatile anesthetic action on muscle Ca2+ homeostasis.
AB  - It is proposed that volatile anesthetics act through the modification of Ca2+
      homeostasis in excitable cells. To test this hypothesis, cardiac and skeletal
      muscles were used as models to examine Ca2+ response, and Ca2+ regulatory and
      delivery mechanisms. I found that halothane did not alter Ca2+ binding to cardiac
      troponin C. However, halothane and isoflurane reversibly decreased the Ca2+
      affinity of calmodulin at low anesthetic concentration, and irreversibly
      increased the Ca2+ affinity of calmodulin at high anesthetic concentration. The
      volatile anesthetics also increased the permeability of light fraction of
      sarcoplasmic reticulum (SR) to Ca2+. I conclude that volatile anesthetics alter
      calcium homeostasis in cardiac and skeletal muscles. This work was in part
      performed in collaboration with Giovanni Salviati and the author benefited from
      Salviati's work in similar areas.

PMID- 10937865
TI  - Highlight: GTP binding proteins--central regulators in cell biology.

PMID- 10937866
TI  - Signal transduction and post-transcriptional gene expression.
AB  - Traditionally, growth factor-coupled signaling to the nucleus has been thought to
      be primarily directed toward transcriptional regulation. However, there are now
      increasing indications from a diversity of experimental systems that other
      aspects of RNA processing, including translation, lifetime and stability, and
      splicing are under strict growth factor control. In this review, we present the
      emerging evidence for growth factor signaling pathways that impact on these
      different RNA processing events. Particularly noteworthy is the realization that
      growth factor signaling through Ras can effect the regulation of two RNA cap
      binding proteins, the cytosolic eIF-4E complex, which is necessary for initiating
      translation, and the nuclear cap-binding complex, the CBC, which plays a role in
      cap-dependent pre-mRNA splicing, U snRNA export and 3'-end processing. This,
      taken together with other findings that demonstrate the ability of stress
      response pathways and the small G protein, Cdc42, to activate the CBC, raises
      some interesting possibilities regarding how signaling to the two cellular RNA
      cap-binding protein complexes may coordinate the growth-coupled regulation of
      gene expression at the level of RNA processing.

PMID- 10937867
TI  - Regulation of GTPases in the bacterial translation machinery.
AB  - Several GTPases participate in bacterial protein biosynthesis. Initiation factor
      2 controls the formation of the ribosomal initiation complex and places initiator
      fMet-tRNAfMet in the ribosomal P-site. Elongation factors Tu and G are
      responsible for codon-specific binding of the aminoacyl-tRNA to the A-site, and
      peptidyl-tRNA to the P-site, respectively, during the elongation phase of protein
      biosynthesis. Release factor 3, a GTPase which is not ubiquitous, is involved in
      termination and release of the nascent polypeptide. Other translation factors,
      including initiation factors 1 and 3, elongation factor Ts, release factors 1 and
      2, and ribosomal release factor do not belong to the family of GTP/GDP binding
      proteins. The guanosine nucleotide binding domains of the GTPases involved in
      translation are structurally related to the Galpha subunit of heterotrimeric G
      proteins and to the proteins of the Ras family. We have identified and sequenced
      all genes coding for translation factors in the extreme thermophile Thermus
      thermophilus. The proteins were overproduced in Escherichia coli, purified,
      biochemically characterised and used for crystallisation and structural analysis.
      Further biochemical investigations were aimed at gaining insight into the
      molecular mechanism underlying the regulation of the GTPase activity of the
      translation factors, and to elucidate the role of their ribosomal binding sites
      in this process.

PMID- 10937868
TI  - GTPases mechanisms and functions of translation factors on the ribosome.
AB  - The elongation factors (EF) Tu and G and initiation factor 2 (IF2) from bacteria
      are multidomain GTPases with essential functions in the elongation and initiation
      phases of translation. They bind to the same site on the ribosome where their low
      intrinsic GTPase activities are strongly stimulated. The factors differ
      fundamentally from each other, and from the majority of GTPases, in the
      mechanisms of GTPase control, the timing of Pi release, and the functional role
      of GTP hydrolysis. EF-Tu x GTP forms a ternary complex with aminoacyl-tRNA, which
      binds to the ribosome. Only when a matching codon is recognized, the GTPase of EF
      Tu is stimulated, rapid GTP hydrolysis and Pi release take place, EF-Tu
      rearranges to the GDP form, and aminoacyl-tRNA is released into the
      peptidyltransferase center. In contrast, EF-G hydrolyzes GTP immediately upon
      binding to the ribosome, stimulated by ribosomal protein L7/12. Subsequent
      translocation is driven by the slow dissociation of Pi, suggesting a mechano
      chemical function of EF-G. Accordingly, different conformations of EF-G on the
      ribosome are revealed by cryo-electron microscopy. GTP hydrolysis by IF2 is
      triggered upon formation of the 70S initiation complex, and the dissociation of
      Pi and/or IF2 follows a rearrangement of the ribosome into the elongation
      competent state.

PMID- 10937869
TI  - The role of heterotrimeric G proteins in platelet activation.
AB  - Activation of platelets plays a central role in hemostasis as well as in various
      thromboembolic diseases like myocardial infarction or stroke. Most platelet
      activating stimuli function through receptors which couple to heterotrimeric G
      proteins of the Gi, Gq and G12 families. Recent studies have elucidated the roles
      of individual G proteins in the regulation of platelet functions like shape
      change, aggregation and granule secretion. The signaling pathways mediated by
      heterotrimeric G proteins operate synergistically to induce a full activation of
      platelets. This review summarizes recent progress in the understanding of
      upstream regulation of platelet activation through G protein-coupled receptors.

PMID- 10937870
TI  - Upstream and downstream of ran GTPase.
AB  - Among the Ras family, Ran is a unique small G protein. It does not have a lipid
      modification motif at the C-terminus to bind to the membrane, which is often
      observed within the Ras family. Ran may therefore interact with a wide range of
      proteins in various intracellular locations. This means that Ran could play many
      different roles like nucleocytoplasmic transport, microtubule assembly and so on.
      All of the Ran functions should be regulated by RanGEF and RanGAP. It is an
      interesting issue why RCC1, a RanGEF, is localized in the nucleus and
      RanGAP1/Ran1p in the cytoplasm. It is possible that RCC1 checks the state of
      chromosomal DNA replication and transfers it to the downstream events through
      Ran; thereby, RCC1 would be involved in coupling the spatial localization of
      cellular macromolecules with the cell cycle progression. In this context, Ran
      will be a very important cell cycle mediator. There is yet another G protein
      cascade, Gtr1-Gtr2, which interacts with the Ran cycle.

PMID- 10937871
TI  - Nogo-A, a potent inhibitor of neurite outgrowth and regeneration.
AB  - The lack of regrowth of injured neurons in the adult central nervous system (CNS)
      of higher vertebrates was accepted as a fact for many decades. In the last few
      years a very different view emerged; regeneration of lesioned fibre tracts in
      vivo could be induced experimentally, and molecules that are responsible for
      inhibition and repulsion of growing neurites have been defined. Mechanisms that
      link cellular phenomena like growth cone turning or growth cone collapse to
      intracellular changes in second messenger systems and cytoskeletal dynamics
      became unveiled. This article reviews recent developments in this field, focusing
      especially on one of the best characterised neurite out-growth inhibitory
      molecules found in CNS myelin that was recently cloned: Nogo-A. Nogo-A is a high
      molecular weight transmembrane protein and an antigen of the monoclonal antibody
      mAb IN-1 that was shown to promote long-distance regeneration and functional
      recovery in vivo when applied to spinal cord-injured adult rats. Nogo-A is
      expressed by oligodendrocytes in white matter of the CNS. With the molecular
      characterisation of this factor new possibilities open up to achieve structural
      and functional repair of the injured CNS.

PMID- 10937872
TI  - Rho GTPases as targets of bacterial protein toxins.
AB  - Several bacterial toxins target Rho GTPases, which constitute molecular switches
      in several signaling processes and master regulators of the actin cytoskeleton.
      The biological activities of Rho GTPases are blocked by C3-like transferases,
      which ADP-ribosylate Rho at Asn41, but not Rac or Cdc42. Large clostridial
      cytotoxins (e. g., Clostridium difficile toxin A and B) glucosylate Rho GTPases
      at Thr37 (Rho) or Thr35 (Rac/Cdc42), thereby inhibiting Rho functions by
      preventing effector coupling. The 'injected' toxins ExoS, YopE and SptP from
      Pseudomonas aeruginosa, Yersinia and Salmonella ssp., respectively, which are
      transferred into the eukaryotic target cells by the type-III secretion system,
      inhibit Rho functions by acting as Rho GAP proteins. Rho GTPases are activated by
      the cytotoxic necrotizing factors CNF1 and CNF2 from Escherichia coli and by the
      dermonecrotizing toxin DNT from B. bronchiseptica. These toxins
      deamidate/transglutaminate Gln63 of Rho to block the intrinsic and GAP-stimulated
      GTP hydrolysis, thereby constitutively activating the GTPases. Rho GTPases are
      also activated by SopE, a type-III system injected protein from Salmonella ssp.,
      that acts as a GEF protein.

PMID- 10937873
TI  - A conserved Gbeta binding (GBB) sequence motif in Ste20p/PAK family protein
      kinases.
AB  - Serine/threonine protein kinases of the Ste20p/PAK family are highly conserved
      from yeast to man. These protein kinases have been implicated in the signaling
      from heterotrimeric G proteins to mitogen-activated protein (MAP) kinase cascades
      and to cytoskeletal components such as myosin-I. In the yeast Saccharomyces
      cerevisiae, Ste20p is involved in transmitting the mating-pheromone signal from
      the betagamma-subunits of a heterotrimeric G protein to a downstream MAP kinase
      cascade. We have previously shown that binding of the G-protein beta-subunit
      (Gbeta) to a short binding site in the non-catalytic carboxy-terminal region of
      Ste20p is essential fortransmitting the pheromone signal. In this study, we
      searched protein sequence databases for sequences that are similar to the Gbeta
      binding site in Ste20p. We identified a sequence motif with the consensus
      sequence S S L phi P L I/V x phi phi beta (x: any residue; phi: A, I, L, S, or T;
      beta: basic residues) that is solely present in members of Ste20p/PAK family
      protein kinases. We propose that this sequence motif, which we have designated
      GBB (Gbeta binding) motif, is specifically responsible for binding of Gbeta to
      Ste20p/PAK protein kinases in response to activation of heterotrimeric G protein
      coupled receptors. Thus, the GBB motif is a novel type of signaling domain that
      serves to link protein kinases of the Ste20p/PAK family to G protein coupled
      receptors.

PMID- 10937874
TI  - Identification of a CpG island in the human LRP-2 gene and analysis of its
      methylation status in parathyroid adenomas.
AB  - Methylation of CpG residues in mammalian genomes is a mechanism of vital
      importance for many cellular functions, which all relate to gene expression. In
      this study we describe the identification of a CpG island in the 5'-region of the
      gene encoding human megalin/LRP-2, a receptor capable of binding multiple
      ligands, which is involved in the regulation of calcium metabolism. Southern blot
      analysis and genomic bisulfite sequencing revealed that the CpG island is
      methylated in a non-expressing cell line, largely unmethylated in an expressing
      cell line and unmethylated in human parathyroid tissue. In addition, we show that
      artificial methylation of LRP-2 promoter reporter plasmids leads to strong
      transcriptional repression, in vitro as well as in transfected cells. No evidence
      for aberrant LRP-2 gene methylation in parathyroid adenomas, in which the LRP-2
      protein is generally down-regulated, was found.

PMID- 10937875
TI  - Theoretical description of the direct exponential amplification and sequencing
      (DEXAS) method.
AB  - We present a theoretical description of the method of DNA sequencing with
      simultaneous exponential PCR amplification of the template (DEXAS). Based on the
      theory of probability, the formula determining the optimal ratio of
      concentrations of deoxy- and dideoxynucleotides in the reaction mixture is
      derived, as well as the length distribution of sequenced DNA fragments. The
      prediction of the number of mutations is given and the theoretically determined
      aspects of DEXAS are compared with the corresponding quantities of classical
      sequencing methods. Some other experimentally observed effects are also
      discussed.

PMID- 10937876
TI  - Adenine nucleotide N-glycosidase activity of the A-chain of cinnamomin
      characterized by 1H-nuclear magnetic resonance.
AB  - Plant ribosome-inactivating proteins specifically cleave an N-glycosidic bond of
      a unique adenosine in the largest ribosomal RNA, releasing an adenine from
      ribosomes of different sources. Here, 1H-nuclear magnetic resonance is used to
      analyze the enzymatic products of the A-chain of cinnamomin, a type-II ribosome
      inactivating protein (RIP) acting on the nucleotides in situ. The enzymatic
      activities of the RIP on nine nucleotides are compared. Cinnamomin A-chain can
      cleave the N-glycosidic bond and release an adenine base from adenine nucleotides
      except 5'-ATP; however, it cannot act on 5'-GMP, 5'-CMP, and 5'-UMP. The A-chain
      in the mixture of cinnamomin A- and B-chain exhibits higher activity toward
      adenine nucleotides than the A-chain alone does, suggesting that the B-chain can
      conformationally stabilize the A-chain. Intact cinnamomin also exhibits lower
      activity toward adenine nucleotides. However, cinnamomin B-chain and heat
      denatured intact cinnamomin cannot hydrolyze all the tested nucleotides. We
      conclude that hydrolysis of the N-C glycosidic bond of nucleotide compounds by
      cinnamomin A-chain has a base preference, and the negatively charged phosphate
      group(s) reduces the recognition ability of the A-chain to adenine nucleotide.

PMID- 10937877
TI  - Msb4p, a protein involved in Cdc42p-dependent organization of the actin
      cytoskeleton, is a Ypt/Rab-specific GAP.
AB  - Ypt/Rab proteins of the Ras superfamily are regulators of protein transport in
      exo- and endocytosis. Like Ras and Rho proteins, they have a slow intrinsic
      GTPase activity that can be accelerated by several orders of magnitude by GTPase
      activating proteins (GAP). Here we describe a new member of a family of Ypt/Rab
      specific GAPs, Msb4p/Gyp4p, that shares with other Gyp family members significant
      homology in the catalytic domain, recently identified in Gyp1p and Gyp7p.
      Purified Msb4p/Gyp4p acts primarily on Sec4p, Ypt6p and Ypt7p and might have a
      role in polarized secretion.

PMID- 10937878
TI  - Muscle phosphorylase kinase is not a substrate of AMP-activated protein kinase.
AB  - AMP-activated protein kinase (AMPK) and cAMP-dependent protein kinase (cAMPK)
      have been reported to phosphorylate sites on phosphorylase kinase (PhK). Their
      target residues Ser 1018 and Ser 1020, respectively, are located in the so-called
      multi-phosphorylation domain in the PhK alpha subunit. In PhK preparations, only
      one of these serines is phosphorylated, but never both of them. The aim of this
      study was to determine whether phosphorylation by cAMPK or AMPK would influence
      subsequent phosphorylation by the other kinase. Surprisingly, employing four
      different PhK substrates, it could be demonstrated that, in contradiction to
      previous reports, PhK is not phosphorylated by AMPK.

PMID- 10937879
TI  - Cationic lipopolyamines induce degradation of PrPSc in scrapie-infected mouse
      neuroblastoma cells.
AB  - In prion diseases the endogenous prion protein (PrPC) is converted into an
      abnormally folded isoform, denoted PrPSc, which represents the major component of
      infectious scrapie prions. The mechanism of the conversion is largely unknown,
      but the conversion is thought to occur after PrPC has reached the plasma
      membrane. Here we show that exogenous administration of the cationic
      lipopolyamine DOSPA interfered with the accumulation of PrPSc in scrapie-infected
      neuroblastoma cells. Structural analysis of the compounds tested revealed that
      inhibition of PrPSc was specific for lipids with a headgroup composed of the
      polyamine spermine and a quarternary ammonium ion between the headgroup and the
      lipophilic tail. The cationic lipopolyamine DOSPA induced the cellular
      degradation of preexisting PrPSc aggregates within 12 hours and interfered with
      the de novo synthesis of PrPSc. Biosynthesis of PrPC, or the assembly of
      sphingolipid-cholesterol microdomains (rafts) on the plasma membrane, were not
      affected by this inhibitor. After removal of DOSPA and replating into normal
      medium propagation of PrPSc commenced, although initially at a reduced rate.
      Incubation of ScN2a cells in free spermidine had no inhibitory effect on the
      accumulation of PrPSc. Our results indicate that membrane targeting of a small
      polyamine molecule creates a potent inhibitor of PrPSc propagation and offers the
      possibility to degrade preexisting PrPSc aggregates in living cells.

PMID- 10937880
TI  - Glycosylphosphatidylinositol-specific phospholipase D of human serum--activity
      modulation by naturally occurring amphiphiles.
AB  - The enzymatic properties of glycosylphosphatidylinositol-specific phospholipase D
      (EC 3.1.4.50) were characterized using a 6,000-fold purified enzyme. This was
      obtained in 100 microg amounts from human serum with a recovery of 35%. Pure
      alkaline phosphatase containing one anchor moiety per molecule was used as
      substrate. The enzyme is stimulated by n-butanol, but in contrast to other
      phospholipases this activation is not produced by a transphosphatidylation
      reaction. The previously reported non-linearity of the specific activity with
      respect to phospholipase concentration in the test was no longer observed upon
      purification, indicating inhibitor removal. The serum inhibitor(s) co
      chromatograph with serum proteins and lipoproteins. The main part of the
      inhibitory activity was found in the lipid fraction after protein denaturation
      and can be subfractionated into acid phospholipids, cholesteryl esters and
      triacylglycerides. Added phosphatidyl-serine, phosphatidylinositol,
      phosphatidylglycerol, gangliosides, cholesteryl esters, and sphingomyelins turned
      out to be strong inhibitors, as well as phosphatidic acid.
      Phosphatidylethanolamine and various monoacylglycerols were found to be
      activators. The low glycosylphosphatidylinositol-specific phospholipase activity
      found in native serum did not increase significantly upon 90% removal of
      phospholipids by n-butanol. High serum concentrations of strongly inhibiting
      compounds, complex kinetic interactions among aggregates of these substances, and
      compartmentalization effects are discussed as possible reasons for the observed
      inactivity.

PMID- 10937881
TI  - Retrieval of the mrp2 gene encoded conjugate export pump from the canalicular
      membrane contributes to cholestasis induced by tert-butyl hydroperoxide and
      chloro-dinitrobenzene.
AB  - Oxidative stress is known to induce cholestasis, but the underlying mechanisms
      are poorly understood. In this study we have characterized the short-term effects
      of tert-butyl hydroperoxide (t-BOOH)- and 1-chloro-2,4-dinitrobenzene (CDNB) on
      the mrp2 gene encoded canalicular export pump (Mrp2). The effects of t-BOOH and
      CDNB on bile formation, tissue GSH levels and subcellular Mrp2 localization were
      studied in perfused rat liver. Both, t-BOOH (0.5 mM) and CDNB (0.1 mM) induced
      within 60 min a decrease of hepatic GSH levels by more than 90% and an almost
      complete cessation of bile flow. As revealed by confocal laser scanning
      microscopy, this cholestasis was accompanied by a loss of immunoreactive MRP2
      from the canalicular membrane and its appearance inside the hepatocytes in
      putative intracellular vesicles. On the other hand, the intracellular
      distribution of dipeptidyl peptidase IV (DPPIV), another canalicular protein, and
      of zonula occludens associated polypeptide (ZO-1) remained unaffected, indicating
      selectivity of the Mrp2 retrieval pattern. Both, t-BOOH and CDNB induced a rapid
      net K+ efflux from the liver and a significant decrease of liver cell hydration.
      We conclude that severe glutathione depletion induces cholestasis by a retrieval
      of Mrp2, but not of DPPIV from the canalicular membrane. The underlying mechanism
      is unclear; however, a decrease in liver cell hydration, which occurs under these
      conditions, may contribute to this effect.

PMID- 10937882
TI  - Matrix metalloproteinases-2,-3,-7,-9 and-10, but not MMP-11, are differentially
      expressed in normal, benign tumorigenic and malignant human keratinocyte cell
      lines.
AB  - In order to investigate the correlations between constitutive proteinase
      expression and the degree of tumorigenicity of cancer cells we have studied a
      model system of three keratinocyte cell lines. RT-PCR studies showed that the
      cell lines express the genes of matrix metalloproteinase-2, -3, -7, -9, -10 and 
      11, indicating that they are able to synthesize the corresponding enzymes. Actual
      MMP synthesis was proven by zymography and Western blotting. In conditioned media
      gelatinolytic activities or immunoreactive forms of MMP-2, -3, -7, -9, -10 and 
      11 were detected. The signal intensities showed that MMP secretion increases in
      the order HaCaT < A5 < or = II-4RT, whereas only MMP-11 is secreted by all cell
      lines in equal amounts. Intracellularly, enhanced levels of one or both of the
      tumorigenic variants were only found for MMP-3, -9 and -10, suggesting special
      functions of these intracellular MMP pools for the tumorigenic cell lines. For
      MMP-11 exclusive expression in stromal fibroblasts of tumor tissues is widely
      accepted; however, our results and three other recent reports demonstrate that
      this concept is not generally valid. In conclusion, the three keratinocyte cell
      lines investigated here represent an excellent model for studying constitutive
      expression and secretion of MMPs in correlation to the degree of in vivo
      tumorigenicity.

PMID- 10937883
TI  - Human keratinocyte cell lines differ in the expression of the collagenolytic
      matrix metalloproteinases-1,-8, and -13 and of TIMP-1.
AB  - We investigated cells and conditioned media of the three human keratinocyte cell
      lines HaCaT (non-tumorigenic), A5 (benign, tumorigenic) and II-4RT (malignant,
      tumorigenic) with regard to production and secretion of the collagenases-1 to -3
      (MMP-1, MMP-8 and MMP-13) and TIMP-1 using semi-nested RT-PCR, Western blots,
      ELISA, immunocytochemistry and casein zymography. Transcripts of MMP-1, -8, -13
      and TIMP-1 were detected in all cell lines by RT-PCR and the corresponding
      proteins were found in the cytoplasm of all three cell lines by Western blot
      analysis and/or immunocytochemistry. The conditioned media of the malignant II
      4RT cells contain significantly more MMP-1 and MMP-8 than those of HaCaT or A5 as
      evidenced by immunoblotting and ELISA. In addition to the presence of latent MMP
      1, zymography also detected the active form of this enzyme. TIMP-1 was found only
      in extracts of all three cell lines, predominantly in A5. This study clearly
      indicates that the epithelial tumor cells synthesize different collagenases and
      TIMP-1. The malignant clone secretes increased amounts of distinct collagenases
      compared to the non-tumorigenic cell line, thereby verifying a correlation
      between biological behaviour and the amount of collagenases. In addition, we
      provide clear evidence that MMP-8 is not exclusively found in polymorphonuclear
      granulocytes, but also in keratinocyte cell lines.

PMID- 10937884
TI  - Inducibility of the Streptomyces traRts107-Ptra expression cassette in
      Mycobacterium smegmatis.
AB  - An inducible Streptomyces expression cassette utilising the Ptra promoter and a
      temperature-sensitive allele of the TraR repressor from S. nigrifaciens plasmid
      pSN22 was tested in Mycobacterium smegmatis. Using reporter assays and Northern
      blot analysis, a marked increase of Ptra-directed transcription was observed upon
      a temperature shift from 28 to 37 degrees C. These results show that the S.
      nigrifaciens promoter-repressor cassette is functional in M. smegmatis. However,
      comparison of the level of induced Ptra-directed transcription with the level of
      transcription directed by the strong mycobacterial promoter Phsp60 indicated that
      the relative strength of the Ptra promoter was low. Considering the severe
      limitation of inducible expression systems for mycobacteria, this Streptomyces
      cassette might be a useful starting point for the development of a compact and
      fully portable inducible mycobacterial expression cassette.

PMID- 10937885
TI  - Shortest known prion protein allele in highly BSE-susceptible lemurs.
AB  - We describe the shortest prion protein allele known to date. Surprisingly, it is
      found as a polymorphism exactly in a species (prosimian lemurs) which seems
      highly susceptible to oral infection with BSE-derived prions. The truncation of
      the prion protein we found raises several questions. First, is the truncated
      octarepeat structure we describe, consisting of two octarepeats, still functional
      in copper binding? A second question is whether this truncation is related to the
      remarkable oral infectibility of lemurs with BSE-derived prions. And finally, one
      could argue that this genotype alone might favour development of a prion disease,
      even in the absence of exogenous infection.

PMID- 10937886
TI  - Prostaglandin deficiency promotes sensitization of adenylyl cyclase.
AB  - Inhibition of prostaglandin synthesis by the drug indomethacin suppresses the
      synthesis of the cyclic AMP antagonist, prostaglandylinositol cyclic phosphate
      (cyclic PIP), and leads to a metabolic state comparable to type II diabetes. It
      was of interest whether prostaglandin-deficiency likewise causes sensitization of
      adenylyl cyclase, as this has been reported for the diabetic state. In liver
      plasma membranes of indomethacin-treated male rats, basal and forskolin
      stimulated cyclic AMP synthesis remained unchanged when compared to untreated
      control rats. In control rats, stimulation of cyclic AMP synthesis by fluoride
      (2.2-fold) or glucagon (3.5-fold) was much lower than stimulation by forskolin
      (6.6-fold). In contrast, in indomethacin-treated rats, stimulation of cAMP
      synthesis by fluoride (4.6-fold) or glucagon (5.2-fold) nearly matched the
      stimulation by forskolin (6.4-fold). The level of alpha1-adrenergic receptors was
      slightly reduced, from 450 to 320 fmol/mg protein, by the indomethacin treatment.
      Independent of the treatment by indomethacin, stimulation of cyclic AMP synthesis
      by adrenaline failed, in agreement with the low density of adrenergic beta
      receptors. In conclusion, PGE deficiency sensitizes adenylyl cyclase in rat liver
      for G protein-coupled receptors (glucagon) and also for fluoride.

PMID- 10937887
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Trauma systems.
AB  - Published case series and cohort comparison studies of patients treated in
      regions where planned trauma systems are in place compared to regions without
      trauma systems, or before and after instituting a trauma system, conclude that
      mortality is reduced after major trauma in patients treated in a trauma system.
      For optimal care of neurotrauma, neurosurgeons should be involved in the planning
      and implementation of trauma systems and in support of a system once it is in
      place.

PMID- 10937888
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Initial management.
AB  - The fundamental goals of resuscitation of the head-injured patient are the
      restoration of circulating volume, blood pressure, oxygenation, and ventilation.
      The physician should initiate maneuvers that serve to lower ICP and do not
      interfere with these aims as early as possible during resuscitation of any
      patient with a head injury. Treatment modalities such as hyperventilation and
      mannitol administration that have the potential of exacerbating intracranial
      ischemia or interfering with resuscitation should be reserved for patients who
      show signs of intracranial hypertension such as evidence of herniation or
      neurologic deterioration.

PMID- 10937889
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Resuscitation of blood
      pressure and oxygenation.
AB  - Early postinjury episodes of hypotension or hypoxia greatly increase morbidity
      and mortality from severe head injury. At present, defining level of hypotension
      and hypoxia is unclear in these patients. However, ample class II evidence exists
      regarding hypotension, defined as a single observation of a systolic blood
      pressure of <90/mm Hg, or hypoxia, defined as apnea/cyanosis in the field or a
      PaO2 < 60 mm Hg by arterial blood gas analysis, to warrant the formation of
      guidelines stating that these values must be avoided, if possible, or rapidly
      corrected in severe head injury patients. A significant proportion of adult and
      pediatric TBI patients are discovered to be hypoxemic or hypotensive in the
      prehospital setting. Patients with severe head injury that are intubated in the
      prehospital setting appear to have better outcomes. Strong class II evidence
      suggests that raising the blood pressure in hypotensive, severe head injury
      patients improves outcome in proportion to the efficacy of the resuscitation.

PMID- 10937890
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Indications for intracranial
      pressure monitoring.
AB  - ICP monitoring per se has never been subjected to a prospective randomized
      clinical trial (PRCT) to establish its efficacy (or lack thereof) in improving
      outcome from severe head injury. Hence, there are insufficient data to support
      its use as a standard. However, there is a large body of published clinical
      experience that indicates that ICP monitoring (1) helps in the earlier detection
      of intracranial mass lesions, (2) can limit the indiscriminate use of therapies
      to control ICP which themselves can be potentially harmful, (3) can reduce ICP by
      CSF drainage and thus improve cerebral perfusion, (4) helps in determining
      prognosis, and (5) may improve outcome. ICP monitoring is therefore used by most
      head injury experts in the United States and is accepted as a relatively low-risk
      high-yield, modest cost intervention. Comatose head injury patients (GCS 3-8)
      with abnormal CT scans should undergo ICP monitoring. Comatose patients with
      normal CT scans have a much lower incidence of intracranial hypertension unless
      they have two or more of the following features at admission: age over 40,
      unilateral or bilateral motor posturing, or a systolic blood pressure of less
      than 90 mm Hg. ICP monitoring in patients with a normal CT scan with two or more
      of these risk factors is suggested as a guideline. Routine ICP monitoring is not
      indicated in patients with mild or moderate head injury. However, it may be
      undertaken in certain conscious patients with traumatic mass lesions at the
      discretion of the treating physician.

PMID- 10937891
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Intracranial pressure
      treatment threshold.
AB  - An absolute ICP threshold that is uniformly applicable is unlikely to exist.
      Current data, however, support 20-25 mm Hg as an upper threshold above which
      treatment to lower ICP should generally be initiated.

PMID- 10937892
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Recommendations for
      intracranial pressure monitoring technology.
AB  - In patients who require ICP monitoring, a ventricular catheter connected to an
      external strain gauge transducer or catheter tip pressure transducer device is
      the most accurate reliable method of monitoring ICP and enables therapeutic CSF
      drainage. Clinically significant infections or hemorrhage associated with ICP
      devices causing patient morbidity are rare and should not deter the decision to
      monitor ICP. Parenchymal catheter tip pressure transducer devices measure ICP
      similar to ventricular ICP pressure but have the potential for significant
      measurement differences and drift due to the inability to recalibrate. These
      devices are advantageous when ventricular ICP is not obtained or if there is
      obstruction in the fluid couple. Subarachnoid or subdural fluid coupled devices
      and epidural ICP devices are currently less accurate.

PMID- 10937893
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Guidelines for cerebral
      perfusion pressure.
AB  - Maintenance of a CPP above 70 mm Hg is a therapeutic option that may be
      associated with a substantial reduction in mortality and improvement in quality
      of survival and is likely to enhance perfusion to ischemic regions of the brain
      following severe TBI. No study has demonstrated that the incidence of
      intracranial hypertension, morbidity, or mortality is increased by the active
      maintenance of CPP above 70 mm Hg, even if this means normalizing the
      intravascular volume or inducing systemic hypertension.

PMID- 10937894
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Hyperventilation.
AB  - Chronic prophylactic hyperventilation therapy should be avoided during the first
      5 days after severe TBI and particularly during the first 24 h. CBF measurements
      in patients with severe TBI demonstrate that blood flow early after injury is low
      and strongly suggest that in the first few hours after injury the absolute values
      approach those consistent with ischemia. These findings are corroborated by AVdO2
      and SjO2 and brain tissue O2 measurements. Hyperventilation will reduce CBF
      values even further, but will not consistently cause a reduction of ICP and may
      cause loss of autoregulation. The cerebral vascular response to hypocapnia is
      reduced in those with the most severe injuries (subdural hematomas and diffuse
      contusions), and there is substantial local variability in perfusion. While the
      CBF level at which irreversible ischemia occurs has not been clearly established,
      ischemic cell change has been demonstrated in 90% of those who die following TBI,
      and there is PET evidence that such damage is likely to occur when CBF drops
      below 15-20 cc/100 g/min. A prospective randomized clinical trial has determined
      that outcomes are worse when TBI patients are treated with chronic prophylactic
      hyperventilation therapy. Within the standard, guideline, and options, specific
      paCO2 thresholds have been described that are different for each of the three
      parameters. These individual thresholds were selected based on the preponderance
      of literature supporting those thresholds in the contexts of the statements which
      included them. With the exception of the threshold included for the standard in
      this guideline, it is emphasized that the paCO2 threshold is not as important as
      the general concept of hyperventilation. The preponderance of the physiologic
      literature concludes that hyperventilation during the first few days following
      severe traumatic brain injury, whatever the threshold, is potentially deleterious
      in that it can promote cerebral ischemia.

PMID- 10937895
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Use of mannitol.
AB  - There are two "class 1" studies, and one "class 2" study, and a large body of
      "Class 3" data, which can be used to support mannitol. The evidence supporting
      use of mannitol for ICP control is sufficiently strong to warrant guideline
      status. Mannitol is effective in reducing ICP, and its use is recommended as a
      guideline in the management of traumatic intracranial hypertension. Serum
      osmolalities >320 mOsm and hypovolemia should be avoided. There is some data to
      suggest that bolus administration is preferable to continuous infusion.

PMID- 10937896
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Use of barbiturates in the
      control of intracranial hypertension.
AB  - High-dose barbiturate therapy is efficacious in lowering ICP and decreasing
      mortality in the setting of uncontrollable ICP refractory to all other
      conventional medical and surgical ICP-lowering treatments. Utilization of
      barbiturates for the prophylactic treatment of ICP is not indicated. The
      potential complications attendant on this form of therapy mandate that its use be
      limited to critical care providers and that appropriate systemic monitoring be
      undertaken to avoid or treat any hemodynamic instability. When barbiturate coma
      is utilized, consideration should also be given to monitoring arteriovenous
      oxygen saturation as some patients treated in this fashion may develop oligemic
      cerebral hypoxia.

PMID- 10937897
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Role of steroids.
AB  - The majority of available evidence indicates that steroids do not improve outcome
      or lower ICP in severely head-injured patients. The routine use of steroids is
      not recommended for these purposes.

PMID- 10937898
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Critical pathway for the
      treatment of established intracranial hypertension.

PMID- 10937899
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Nutrition.
AB  - Data show that starved head-injured patients lose sufficient nitrogen to reduce
      weight by 15% per week. Class II data show that 100-140% replacement of resting
      metabolism expenditure with 15-20% nitrogen calories reduces nitrogen loss. Data
      in non-head injured patients show that a 30% weight loss increased mortality
      rate. Class I data suggests that nonfeeding of head-injured patients by the first
      week increases mortality rate. The data strongly support feeding at least by the
      end of the first week. It has not been established that any method of feeding is
      better than another or that early feeding prior to 7 days improves outcome. Based
      on the level of nitrogen wasting documented in head-injured patients and the
      nitrogen sparing effect of feeding, it is a guideline that full nutritional
      replacement be instituted by day 7.

PMID- 10937901
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Methodology.

PMID- 10937900
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Role of antiseizure
      prophylaxis following head injury.
AB  - The majority of studies do not support the use of the prophylactic
      anticonvulsants studied thus far for the prevention of late PTS. Routine seizure
      prophylaxis later than 1 week following head injury is, therefore, not
      recommended. If late PTS occur, patients should be managed in accordance with
      standard approaches to patients with new onset seizures. Phenytoin and
      carbamazepine have been shown to reduce the incidence of early PTS. Valproate may
      also have a comparable effect to phenytoin on reducing early PTS but may also be
      associated with a higher mortality. It is, therefore, an option to use phenytoin
      or carbamazepine to prevent the occurrence of seizures in high-risk patients
      during the first week following head injury.

PMID- 10937902
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Glasgow coma scale score.
AB  - When considering the use of the initial GCS for prognosis, the two most important
      problems are the reliability of the initial measurement, and its lack of
      precision for prediction of a good outcome if the initial GCS is low. If the
      initial GCS is reliably obtained and not tainted by prehospital medications or
      intubation, approximately 20% of the patients with the worst initial GCS will
      survive and 8-10% will have a functional survival (GOS 4-5).

PMID- 10937903
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Age.
AB  - Age is a strong factor influencing both mortality and morbidity. Despite some
      contradictions, most literature supports children faring better than adults who
      have severe brain injury. The significant influence of age upon outcome is not
      explained by the increased frequency of systemic complications or intracerebral
      hematomas with age. Increasing age is a strong independent factor in prognosis,
      with a significant increase in poor outcome above 60 years of age.

PMID- 10937904
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Pupillary diameter and light
      reflex.
AB  - The pupillary diameter and the pupilloconstrictor light reflex are the two
      parameters that have been studied extensively in relation to prognosis. Accurate
      measurement of pupil diameter or the constrictor response or the duration of the
      response has not been performed in studies on traumatic brain-injured individuals
      -for lack of a standardized measuring procedure. The following is recommended: 1.
      Pupillary light reflex for each eye should be used as a prognostic parameter. 2.
      The duration of pupillary dilation and fixation should be documented. 3. A
      pupillary size of >4 mm is recommended as the measure for a dilated pupil. 4. A
      fixed pupil should be defined as no constrictor response to bright light. 5.
      Right or left distinction should be made when the pupils are asymmetric. 6.
      Hypotension and hypoxia should be corrected before assessing pupils for
      prognosis. 7. Direct orbital trauma should be excluded. 8. Pupils should be
      reassessed after surgical evacuation of intracranial hematomas.

PMID- 10937905
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Hypotension.
AB  - Hypotension, occurring at any time from injury through the acute intensive care
      course, has been found to be a primary predictor of outcome from severe head
      injury for the health care delivery systems within which prognostic variables
      have been best studied. Hypotension is repeatedly found to be one of the five
      most powerful predictors of outcome and is generally the only one of these five
      that is amenable to therapeutic modification. A single recording of a hypotensive
      episode is generally associated with a doubling of mortality and a marked
      increase in morbidity from a given head injury. The estimated reduction in
      unfavorable outcome that would result from the elimination of hypotensive
      secondary brain insults is profound.

PMID- 10937906
TI  - The Brain Trauma Foundation. The American Association of Neurological Surgeons.
      The Joint Section on Neurotrauma and Critical Care. Computed tomography scan
      features.

PMID- 10937907
TI  - Comparison of argon and CO2 laser stapedotomy in primary otosclerosis surgery.
AB  - PURPOSE: The primary use for the laser in otosclerosis surgery is to create a
      stapes footplate fenestration that obviates the need for mechanical footplate
      removal. Experimental studies that evaluate the potential safety of visible
      (argon and potassium-titanyl-phosphate [KTP]) and invisible (CO2) light laser
      systems in stapes surgery report conflicting results. The purpose of this study
      is to compare the clinical safety and efficacy of the CO2 and argon laser systems
      when used for primary laser stapedotomy. MATERIALS AND METHODS: A retrospective
      case review of 124 primary laser stapedotomies using either the argon (n = 59) or
      CO2 (n = 65) laser was performed. Data consisted of pre- and postoperative air
      and bone conduction audiometry, speech discrimination scores (SDS),
      intraoperative findings, and postoperative complications. Between group
      differences (argon v CO2) were sought using standard statistical methodology.
      RESULTS: The argon and CO2 laser groups were comparable with regards to age, sex,
      preoperative air-bone gap, and laterality. Mean preoperative air and bone
      conduction pure-tone average (PTA) and SDS were somewhat higher in the CO2 laser
      group (P < .05). Postoperatively, both groups showed similar results in mean
      change in air conduction PTA, air-bone gap, and SDS, as well as in the frequency
      of complications. There were no anacoustic ears in either group. CONCLUSIONS: The
      results suggest that the argon and CO2 laser systems are comparable with regards
      to safety and efficacy when used by experienced surgeons for stapedotomy.

PMID- 10937908
TI  - Open rhinoplasty: effectiveness of different tripplasty techniques to increase
      nasal tip projection.
AB  - PURPOSE: To study the effectiveness of 3 different tipplasty techniques to
      increase nasal tip projection (NTP). MATERIALS AND METHODS: NTP of 61 patients
      who underwent open rhinoplasty were retrospectively studied in 3 different
      tipplasty techniques used to increase NTP. Using a standard measurement
      technique, the preoperative and postoperative NTP ratio was measured for every
      patient preoperatively and at least 1 year after surgery. The study population of
      61 patients was divided into 3 groups. Group 1 (n-32) underwent the author's
      routine nasal tip procedure (columellar strut, conservative cephalic trim of the
      lateral crura, and transdomal mattress sutures). Group 2 (n = 10) underwent the
      routine procedure and, in addition, has further medical recruitment of the
      lateral crura. Group 3 (n = 19) underwent the routine procedure and, in addition,
      has a tip cartilage graft. RESULTS AND CONCLUSION: The mean gain NTP
      postoperatively was highest in group 3 and lowest in group 1, and this was
      statistically significant. Causes of these differences in the NTP gain are
      discussed.

PMID- 10937910
TI  - Opioids and their proper use as analgesics in the management of head and neck
      cancer patients.
AB  - Opioid analgesics play an important part in the interdisciplinary management of
      head and neck cancer patients. Acute pain during the initial treatment period and
      chronic pain after treatment may be undertreated by head and neck surgeons
      because of unwarranted fear of the opioid side effects and toxicities. Properly
      used, opioid analgesics are among the safest and most effective medications in
      the armamentarium of the head and neck surgeon. Knowledge of opioid pharmacology
      can help surgeons treat pain aggressively in patients while managing side effects
      and toxicities. This understanding can also address the unique problems in pain
      management presented in head and neck cancer patients attributable to the
      involvement by the disease of the aerodigestive tract, which interferes with the
      oral route of administration of opioid analgesics. Significant difficulties in
      the use of opioid analgesics arise when the patient is a substance abuser. This
      article discusses the basic principles of opioid pharmacology, discusses opioid
      use in head and neck cancer patients, and provides guidelines on the use of
      opioids in the substance abuser.

PMID- 10937909
TI  - Hemangiopericytoma of the head and neck.
AB  - PURPOSE: To report a series of patients with hemangiopericytoma (HP) of the head
      and neck, to review pathological features of these tumors, and to discuss
      management options. MATERIALS AND METHODS: A retrospective review of the medical
      records at the University of California, Los Angeles (UCLA) Medical Center in Los
      Angeles, CA, was done in order to identify those patients with primary HP of the
      head and neck, including soft tissue and mucosal sites. RESULTS: Ten patients
      with HP of the head and neck were identified. There was an equal sex distribution
      and an average age of 36 (range 10-65). Seven of the tumors arose from soft
      tissue sites in the head and neck, and the remaining 3 arose from the mucosa. All
      patients underwent wide excision of the primary lesion with a local recurrence
      rate of 40%. Thirty percent of patients developed metastatic lung disease 0 to 8
      years after initial diagnosis. Each patient who developed metastatic disease had
      abundant mitoses on pathological review compared with rare or absent mitoses in
      the lesions that took a more benign course. CONCLUSIONS: Pathological appearance
      of resected HP is predictive of later metastatic potential. Long-term follow-up
      is necessary in patients even after radical resection because recurrence or
      metastasis may be delayed by many years.

PMID- 10937911
TI  - The challenge of esophagoscopy in infants with open safety pin in the esophagus:
      report of two cases.
AB  - Among all foreign bodies impacted at the esophagus, the safety pin still seems to
      be a challenge for the specialist. This is a report of 2 cases presenting infants
      with open safety pin impacted in the esophagus. The strategy and intraoperative
      management of this rare finding is discussed in detail.

PMID- 10937912
TI  - Extracranial internal carotid artery pseudoaneurysm.

PMID- 10937914
TI  - Mucosa-associated lymphoid tissue lymphoma of the lingual tonsil.

PMID- 10937913
TI  - Preoperative assessment of obstruction with computed tomography image analysis.

PMID- 10937916
TI  - Submasseteric abscess: report of two cases.
AB  - Submasseteric abscess is a rare infection with the symptoms of cheek tenderness
      and marked trismus. Submasseteric abscess is located between the masseter muscle
      and mandibular ramus with different appearances as sepsis, infection, or tumor.
      Two cases of submasseteric abscess are reported along with symptoms, causes, and
      management techniques. Adequate drainage and antibiotic infusion are the
      treatment of choice. The differential diagnosis of cheek swelling and tenderness
      that should be considered are parotitis, parotid gland tumor, temporomasseter
      joint arthritis, and submasseteric abscess.

PMID- 10937915
TI  - Hodgkin's disease simulating a pediatric thyroglossal duct cyst.

PMID- 10937917
TI  - Executive control functions in degenerative dementias: a comparative review.
AB  - This paper reviews the literature concerning executive control impairments in
      degenerative dementias. The construct of executive control functioning is
      examined, as is the neuroanatomy of frontal-subcortical networks, believed to
      underlie executive function (EF) impairments. The pattern of EF impairments in
      Alzheimer's disease (AD) which affects temporal and parietal brain regions most
      severely is contrasted with observed executive dysfunctions in patients with
      dementias involving degeneration of primarily frontal and frontal-subcortical
      brain areas. EF impairments are present in each of these types of dementing
      illnesses. Although EF impairments are present in AD, they are less prominent
      than the memory disorder in the neuropsychological profile of the disease and
      tend to become more pronounced later in the course of the illness. In contrast,
      patients with frontal or frontal-subcortical dementia may demonstrate executive
      dysfunction, which occurs earlier in the disease progression and may be initially
      more severe.

PMID- 10937918
TI  - Frontal-lobe involvement in spatial memory: evidence from PET, fMRI, and lesion
      studies.
AB  - Many studies have identified the prefrontal cortex as the brain area that is
      critical for spatial memory, both in humans and in other primates. Other studies,
      however, have failed to establish this relation. Therefore, the aim of this paper
      was to review the literature regarding the role of the human prefrontal lobe in
      spatial memory. This was done by examining the evidence obtained from
      neuropsychological patients and from studies using brain-imaging techniques (PET
      and fMRI). Evidence supporting the notion that the prefrontal cortex is
      extensively involved in spatial working memory was found. The majority of these
      studies, however, suggests that frontal-lobe involvement is not related to the
      type of material that is being processed (e.g., spatial vs. nonspatial), but to
      process-specific functions, such as encoding and retrieval. Theoretically, these
      functions could be linked to the central executive within Baddeley's working
      memory model, or to recent theories that emphasize the various processes that
      play a role in working memory. Also, methodological issues were discussed.
      Further research is needed to enhance our understanding of the precise
      interaction of domain-specific and general processes.

PMID- 10937920
TI  - Genetic aspects of heart failure.
AB  - Heart failure is a major health problem and is associated with a high mortality
      and morbidity. Recently, the role of the genetic background in the onset and the
      development of the disease has been evidenced in both heart failure with and
      without systolic dysfunction and in familial and non-familial forms of this
      condition. Preliminary studies suggest that the I/D polymorphism of the
      Angiotensin Converting Enzyme gene influence the development of left ventricular
      hypertrophy, a major determinant of heart failure. Familial hypertrophic
      cardiomyopathy (FHC) is a highly heterogenous autosomal dominant disease. Seven
      genes have been identified which all encode proteins of the sarcomere or proteins
      involved in the regulation of contraction. More than one hundred mutations have
      been evidenced. Modifier genes such as the I/D polymorphism seem to play a role
      in the expression of the disease. Susceptibility genes have been searched for in
      sporadic forms of dilated cardiomyopathy and conflicting results have been
      published with regard to the I/D polymorphism. Finally, familial forms of dilated
      cardiomyopathy (FDC) are frequent. Various modes of inheritance and phenotypes
      have been reported and this condition appears genetically highly heterogenous. It
      has been postulated that the molecular defect involved in FDC is an abnormality
      in the transmission of contractile force. The analysis of genetic factors that
      predispose to heart failure looks promising: it should allow better understanding
      of the underlying mechanisms that promote the progression of the disease, to
      identify subjects at risk of the disease who would benefit from early medical
      management and promote the development of pharmacogenetics.

PMID- 10937921
TI  - Heart failure as a metabolic problem.
AB  - Chronic heart failure (CHF) remains an important and increasing public health
      care problem. Not until recently it has been recognised that CHF is a chronic
      progressive disorder affecting different physiological and metabolic pathways.
      Nowadays CHF is reviewed as the consequence of an interplay of haemodynamic,
      neurohormonal, immunological, and endocrine mechanisms, initially thought to have
      beneficial adaptive effects for the organism to compensate the heart's inability
      to pump properly. However, these secondary changes eventually contribute to
      further deterioration of CHF. This review focuses on metabolic features observed
      in patients with CHF and discusses immunological and neuroendocrine aspects and
      their potential contribution to the pathogenesis of CHF. The overall evidence
      suggests that advanced CHF is a multifactorial metabolic syndrome that can lead
      to cardiac cachexia and then carries a very poor prognosis. Joint efforts of
      cardiologists, endocrinologists, and immunologists are required to develop
      therapeutic strategies able to improve the metabolic status of CHF patients.

PMID- 10937919
TI  - Traumatic brain injury as a risk factor for Alzheimer's disease: a review.
AB  - Accumulating epidemiological evidence implicates traumatic brain injury as a
      pathogenic agent in the development of Alzheimer's disease (AD). Considering the
      increase in the prevalence of both traumatic brain injury and AD in recent times,
      the possibility that brain trauma may provoke the early development of AD has
      important implications for health service planning, preventative efforts, and
      medico-legal compensation settlements. This paper evaluates the plausibility of
      the proposed link between traumatic brain injury and AD, largely by way of
      exploring a theoretical perspective advanced by Satz (1993) and considering
      recent contributions from the epidemiological, neuropathological, and biochemical
      literature that are pertinent to this issue. The literature reviewed provides
      sufficient support and empirical vindication to give credence to the proposed
      association between these two neuropsychological entities at the statistical,
      theoretical, and biological level.

PMID- 10937922
TI  - Treatment of arrhythmias in heart failure.

PMID- 10937923
TI  - Increasing awareness and improving the management of heart failure in Europe: the
      IMPROVEMENT of HF initiative.
AB  - BACKGROUND: Previous reports suggest that patients with suspected heart failure
      are inadequately investigated and that patients who do have heart failure are sub
      optimally treated. Guidelines on the diagnosis and treatment of heart failure
      have been published by the European Society of Cardiology and provide a framework
      for the management of heart failure against which to judge current medical
      practice. Both primary care and hospital physicians are responsible for ensuring
      appropriate management of patients with heart failure. This programme
      concentrates on management of heart failure in primary care and is complementary
      to a similar exercise that will be conducted in 50 European regions (EUROHEART
      CHF). AIMS: The IMPROVEMENT of HF initiative investigates, in Europe, how primary
      care physicians perceive heart failure should be diagnosed and treated and
      whether they perceive that they are provided with adequate support to implement
      best medical practice. Subsequently, their perceptions are compared to their
      actual practice by reviewing relevant case notes. The results will be used to
      recommend changes in practice. A future study is planned to analyse the impact of
      the initiative. METHODS: The initiative comprises a research phase and an
      educational phase. For the research phase, 10 regional centres (to include both
      urban and rural areas) from each of 14 participating countries have been
      identified and each region has randomly selected 10 primary healthcare
      physicians. The primary healthcare physicians are participating in two surveys: a
      'perception' survey and an 'actual practice' survey. For the 'actual practice'
      survey, the physicians are supplying case notes of nine patients who have or are
      at high risk of having heart failure. The results of these surveys will be used
      to organise an educational programme. CONCLUSION: This study is expected to
      provide valuable data on the perceptions of primary care physicians about heart
      failure, possible deficiencies in the current provision of care and how any
      deficiencies may be corrected.

PMID- 10937924
TI  - Non-compliance and knowledge of prescribed medication in elderly patients with
      heart failure.
AB  - AIMS: To determine the extent of non-compliance to prescribed medication in
      elderly patients with heart failure and to determine to what extent patients
      recall information given regarding their medication. METHODS AND RESULTS: Non
      compliance and knowledge of prescribed medication was studied in 22 elderly heart
      failure patients [mean age 79 +/- 6 (range 70-97); 14 (64%) male], using in-depth
      interviews performed 30 days after having been prescribed medication. All
      patients received standardised verbal and written information regarding their
      medication. Only 12 (55%) patients could correctly name what medication had been
      prescribed, 11 (50%) were unable to state the prescribed doses and 14 (64%) could
      not account for when the medication was to be taken, i.e. at what time of day and
      when in relation to meals the medication was to be taken. In the overall
      assessment six (27%) patients were found non-compliant and 16 (73%) patients were
      considered as possibly being compliant with their prescribed medication.
      CONCLUSIONS: Non-compliance was common in elderly heart failure patients, as were
      shortcomings in patients knowledge regarding prescribed medication, despite
      efforts to give adequate information. There exists a need for alternative
      strategies to improve compliance in these patients.

PMID- 10937925
TI  - Quality of life in older patients with systolic and diastolic heart failure.
AB  - AIMS: To get insight into the quality of life of a clinical practice sample of
      patients with heart failure that are admitted to the hospital. Secondly to
      determine differences between patients with systolic and diastolic dysfunction
      and finally to describe factors relating to quality of life. METHODS: Three
      dimensions of quality of life (functional capabilities, symptoms and psychosocial
      adjustment to illness) were assessed during interviews of 186 patients with
      chronic heart failure. In addition, data on demographic, clinical and self-care
      characteristics were collected and patients completed a 6-min walk. RESULTS: On
      average patients walked 172 m in 6 min and reported functioning in daily life at
      a mean level of 4.5 MET. Patients experienced four different symptoms of heart
      failure. Most of them described dyspnea, fatigue, sleep disturbance and ankle
      oedema. Problems with psychosocial adaptation occurred mostly in social and
      vocational domains. Overall well-being of patients was rated as 6.4 on a 10-point
      scale. In regard to quality of life, the only differences between patients with
      systolic and diastolic heart failure was the occurrence of ankle oedema and
      health-care orientation. The variance in components of quality of life were
      partly explained by demographics and clinical characteristics. All three
      dimensions of quality of life were related to ability for self-care. CONCLUSION:
      Patients with heart failure seen in clinical practice are often not comparable to
      patients described in major clinical trials or patients that are admitted for
      transplant evaluation. Their functional capabilities are more compromised, but
      they may have fewer problems with psychosocial adjustment. Patients with normal
      systolic dysfunction also report a low quality of life. It could be important to
      enhance self-care abilities of patients to improve psychosocial adaptation to
      illness.

PMID- 10937926
TI  - The influence of diastolic and systolic function on exercise performance in heart
      failure due to dilated cardiomyopathy or ischemic heart disease.
AB  - BACKGROUND: Peripheral adaptations and ventricular abnormalities influence
      physical performance in chronic heart failure. However, the role of the heart in
      determining exercise capacity has not been completely elucidated. AIMS: To define
      cardiac determinants of exercise capacity in patients with dilated
      cardiomyopathy. METHODS: In 101 patients with heart failure (NYHA class II-III)
      due to primary or ischemic dilated cardiomyopathy we measured peak exercise
      oxygen consumption (Pvo2), left ventricular ejection fraction (EF), left and
      right atrial and ventricular cavity dimensions, mitral and tricuspid flows.
      Patients were subdivided in class A (Pvo2 > 20 ml/min per kg; n = 44), class B
      (Pvo2 16-20 ml/min per kg; n = 42) and class C (Pvo2 < 16 ml/min per kg; n = 15).
      RESULTS: Left ventricular diastolic and systolic dimensions, left atrial
      diameter, right atrial and ventricular areas were greater in class C than in
      class B and A; EF was lower in class C than in the other two classes; mitral peak
      flow velocity at early diastole (PFVE) and the ratio between early and late peak
      flow velocity (PFVE/PFVA) were higher in class C; mitral and tricuspid
      deceleration time (DT) in class B and A significantly exceeded those in class C.
      Peak vo2 was correlated with left and right ventricular dimensions, left atrial
      diameter, EF, mitral PFVE and PFVE/PFVA, mitral and tricuspid DT. Left
      ventricular EF, DT of the mitral valve and left ventricular diastolic diameter
      were independent predictors of peak vo2 at multivariate analysis. CONCLUSIONS: In
      patients with dilated cardiomyopathy Pvo2 is related to left and right
      ventricular dimensions, left and right ventricular filling pattern and EF. Both
      systolic and diastolic dysfunction influence functional capacity.

PMID- 10937927
TI  - No evidence for systolic or diastolic left ventricular dysfunction at rest in
      selected patients with long-term type I diabetes mellitus.
AB  - We assessed left ventricular systolic and diastolic function using pulsed-waved
      Doppler echocardiography in a selected group of 20 patients with insulin
      dependent diabetes mellitus (IDDM) (mean age, 35 +/- 8 years; mean diabetes
      duration, 17 + 7 years). Our patients were free of autonomic neuropathy and major
      micro- or macrovascular complications and had no evidence of ischemic heart
      disease or hypertension. The results were compared with those of 20 age- and sex
      matched control subjects. We found that left ventricular geometry and mass,
      systolic function by M-mode and 2D-echocardiography, isovolumetric relaxation
      time, deceleration time and the PEP/LVET ratio were not significantly different
      between patients and control subjects. Hemodynamic parameters were also not
      significantly different except for a slightly higher heart rate in the patient
      group (75 +/- 11 vs. 68 + 6 bpm, P = 0.019). After correction of A-peak
      velocities for differences in heart rate, there was no significant difference of
      Doppler indices of diastolic left ventricular function between patients and
      control subjects. The absence of significant left ventricular systolic and
      diastolic dysfunction by Doppler echocardiography in our study patients may be
      explained by our patient selection. Left ventricular dysfunction in diabetic
      patients without concomitant hypertensive or ischemic heart disease may only
      occur in conjunction with microvascular disease in other organ systems, with
      autonomic neuropathy or with poor metabolic control.

PMID- 10937928
TI  - Dantrolene sodium improves the force-frequency relationship and beta-adregenic
      responsiveness in failing human myocardium.
AB  - BACKGROUND: Failing human myocardium is characterized by a negative force
      frequency relationship and impaired beta-adrenergic responsiveness which have
      been related to alterations of the intracellular Ca2+ homeostasis. Dantrolene
      sodium is a clinically used drug that modulates myocardial [Ca2+]i handling in
      animal models. This study investigated the effects of dantrolene sodium on
      intracellular Ca2+ handling and contractile function in failing human myocardium.
      METHODS AND RESULTS: Twenty-three muscle strips from human left ventricular
      trabeculae were obtained from patients undergoing heart transplantation for end
      stage heart failure caused by idiopathic dilated cardiomyopathy (n = 15).
      Isometric contraction and intracellular Ca2+ transients (Ca2+ indicator:
      aequorin) were recorded simultaneously. The experiments were performed in three
      separate groups exposed to control condition (n = 8), addition of dantrolene (10
      micromol/l; n = 8), or addition of verapamil (1 micromol/l; n = 7). Isoproterenol
      induced a moderate positive inotropic effect in the control group with a maximal
      increase of developed tension from 10.8 +/- 2.9 to 23.4 +/- 4.7 mN/mm2 and a
      parallel rise in peak systolic [Ca2+]i to a maximum of 1.36 +/- 0.20 micromol/l.
      Dantrolene significantly improved (10.2 +/- 3.8 to 32.4 +/- 0.9 mN/mm2) and
      verapamil blunted (8.3 +/- 2.8 to 17.1 +/- 4.3 mN/mm2) the inotropic response to
      isoproterenol. The diastolic and systolic [Ca2+]i during isoproterenol
      stimulation were slightly lower in the dantrolene group but significantly
      depressed in the verapamil group as compared to the control group. Similarly,
      analyses of force-frequency relationships revealed an improvement of developed
      tension in dantrolene-treated as compared to control preparations whereas the
      peak systolic [Ca2+]i was almost identical. CONCLUSION: Dantrolene improves the
      negative force-frequency relationship and beta-adrenergic responsiveness in
      failing human myocardium. These effects are not accompanied by an additional
      increase in intracellular [Ca2+]i but might be related to modifications of the
      diastolic [Ca2+]i homeostasis.

PMID- 10937929
TI  - Intravenous L-arginine reduces VE/VCO2 slope acutely in patients with severe
      chronic heart failure.

PMID- 10937930
TI  - The carvedilol hibernation reversible ischaemia trial; marker of success
      (CHRISTMAS). The CHRISTMAS Study Steering Committee and Investigators.
AB  - BACKGROUND: Carvedilol improves left ventricular (LV) function when heart failure
      is due to LV systolic dysfunction, but the magnitude of the response is
      heterogeneous among patients with coronary disease, possibly reflecting the
      presence or volume of hibernating myocardium. AIMS: The primary objective of the
      study is to determine whether the presence of hibernating myocardium predicts the
      magnitude of improvement in LV ejection fraction in response to carvedilol among
      patients with heart failure and LV systolic dysfunction due to coronary disease.
      METHODS: The study is a prospective, randomised, parallel-group, double-blind,
      multi-centre study comparing carvedilol and placebo over a period of
      approximately 6 months in the above patient population. The primary end-point is
      the comparison of the mean change, from baseline to the final visit, in
      radionuclide-determined LV ejection fraction among patients on placebo with those
      on carvedilol stratified according to the presence of hibernating myocardium.
      Hibernating status will be determined by a combination of echocardiographic and
      myocardial perfusion (technetium-99m sestamibi) imaging. RESULTS: 255 patients
      have undergone screening tests of which 207 have been randomised so far. The
      study intends to randomise 400 patients and the first report of results is
      expected in 2000. CONCLUSIONS: As far as we are aware this is the first
      randomised controlled trial to investigate the effects of treatment in patients
      stratified according to the presence of hibernating myocardium. The study will
      provide insights into the prevalence of myocardial hibernation, its natural
      history, and its influence on prognosis as well as the interaction between the
      presence of hibernating myocardium and the effects of treatment with carvedilol.

PMID- 10937932
TI  - How patients with heart failure are managed in the United Kingdom.
AB  - Heart failure is a major cause of morbidity and mortality world wide. In the UK
      it is estimated to affect one in ten octogenarians. This obviously imposes a
      large burden on our health care services, and the ageing of our population will
      only exacerbate this. In this article we have attempted to provide a general
      overview of the day to day management of these patients in the United Kingdom.

PMID- 10937931
TI  - Update of REACH-1 and MERIT-HF clinical trials in heart failure. Cardio.net
      Editorial Team.
AB  - BACKGROUND: This article reviews the design and results of REACH-1 (Research on
      Endothelin Antagonism in Chronic Heart Failure) and MERIT (Metoprolol controlled
      and Extended release, Randomised Intervention Trial in congestive Heart Failure),
      two recently reported clinical trials that investigated, respectively, the role
      of a non-selective endothelin antagonist (bosentan) and of a beta-selective
      blocker for the treatment of heart failure. RESULTS: The REACH-1 trial
      demonstrated that initiation of bosentan therapy is associated with an increased
      risk of worsening heart failure. However, long-term therapy with bosentan may
      have improved symptoms and favourably altered the progression of heart failure.
      The MERIT-HF clinical trial indicated that beta-blockade using metoprolol confers
      a significant beneficial effect on total mortality in patients with stable
      chronic heart failure.

PMID- 10937933
TI  - Bioreaction network topology and metabolic flux ratio analysis by biosynthetic
      fractional 13C labeling and two-dimensional NMR spectroscopy.
AB  - Biosynthetically directed fractional 13C labeling of the proteinogenic amino
      acids is achieved by feeding a mixture of uniformly 13C-labeled and unlabeled
      carbon source compounds into a bioreaction network. Analysis of the resulting
      labeling pattern enables both a comprehensive characterization of the network
      topology and the determination of metabolic flux ratios. Attractive features with
      regard to routine applications are (i) an inherently small demand for 13C-labeled
      source compounds and (ii) the high sensitivity of two-dimensional [13C,1H]
      correlation nuclear magnetic resonance spectroscopy for analysis of 13C-labeling
      patterns. A user-friendly program, FCAL, is available to allow rapid data
      analysis. This novel approach, which recently also has been employed in
      conjunction with metabolic flux balancing to obtain reliable estimates of in vivo
      fluxes, enables efficient support of metabolic engineering and biotechnology
      process design.

PMID- 10937934
TI  - Pyruvate metabolism in Lactococcus lactis is dependent upon glyceraldehyde-3
      phosphate dehydrogenase activity.
AB  - Modification of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity from
      Lactococcus lactis was undertaken during batch fermentation on lactose, by adding
      various concentrations of iodoacetate (IAA), a compound which specifically
      inhibits GAPDH at low concentrations, to the culture medium. As IAA concentration
      is increased, GAPDH activity diminishes, provoking a decrease of both the
      glycolytic flux and the specific growth rate. This control exerted at the level
      of GAPDH was due partially to IAA covalent fixation but also to the modified
      NADH/NAD+ ratio. The mechanism of inhibition by NADH/NAD+ was studied in detail
      with the purified enzyme and various kinetic parameters were determined.
      Moreover, when GAPDH activity became limiting, the triose phosphate pool
      increased resulting in the inhibition of pyruvate formate lyase activity, while
      the lactate dehydrogenase is activated by the high NADH/NAD+ ratio. Thus,
      modifying the GAPDH activity provokes a shift from mixed-acid to homolactic
      metabolism, confirming the important role of this enzyme in controlling both the
      flux through glycolysis and the orientation of pyruvate catabolism.

PMID- 10937935
TI  - Metabolic flux analysis elucidates the importance of the acid-formation pathways
      in regulating solvent production by Clostridium acetobutylicum.
AB  - Metabolic flux analysis was used to investigate the roles of the acid formation
      pathways in Clostridium acetobutylicum. The acid formation pathways were revealed
      to serve different roles in wildtype fermentations than previously expected.
      Specifically, enzymes known to catalyze butyrate formation were found to uptake
      butyrate without concomitant production of acetone. This role was further
      corroborated by flux analysis of a recombinant strain overexpressing the butyrate
      formation enzymes. Analysis of wildtype fermentation data also revealed an
      important role for the acetate formation enzymes, namely the cycling of carbon
      between acetate and acetylCoA during the stationary phase. Next, metabolic flux
      analysis was used to compare the patterns of activity in two butyrate kinase
      deficient strains of C. acetobutylicum. The strain developed by gene
      inactivation, PJC4BK, exhibited a shift in acid formation fluxes toward acetate
      while the strain developed by antisense RNA strategies, 824(pRD4), did not
      exhibit such a shift. However, both strains exhibited altered solvent formation
      patterns. PJC4BK exhibited a strong transient enhancement of solvent formation
      fluxes. In contrast, 824(pRD4) exhibited relatively lower levels of solvent
      formation fluxes, although fluxes were sustained over a longer period of time.

PMID- 10937936
TI  - Toward predicting metabolic fluxes in metabolically engineered strains.
AB  - Predicting metabolic fluxes of a genetically engineered organism is an important
      step toward rational pathway design. However, because of various regulatory
      mechanisms, which are complex, often ill-characterized, and sometimes
      undiscovered, predicting metabolic fluxes using kinetic simulation is difficult.
      We propose to incorporate regulatory constraints in flux calculation to allow
      prediction of the steady-state fluxes without complete kinetics. The regulatory
      constraint, in its linear form, is derived from the dynamic metabolic control
      theory and involves the flux control coefficients. It is shown that with these
      constraints, the responses to metabolic perturbation can be predicted.
      Conversely, the regulatory constraints and the control coefficients can be
      determined by comparing the experimental data with the prediction. Therefore,
      this approach may offer a practical direction toward prediction of fluxes for
      metabolically engineered organisms.

PMID- 10937937
TI  - Metabolic analysis of glutamate production by Corynebacterium glutamicum.
AB  - The dynamic behavior of the metabolism of Corynebacterium glutamicum during L
      glutamic acid fermentation, was evaluated by quantitative analysis of the
      evolution of intracellular metabolites and key enzyme concentrations. Glutamate
      production was induced by an increase of the temperature and a final
      concentration of 80 g/l was attained. During the production phase, various other
      compounds, notably lactate, trehalose, and DHA were secreted to the medium.
      Intracellular metabolites analysis showed important variations of glycolytic
      intermediates and NADH, NAD coenzymes levels throughout the production phase. Two
      phenomena occur during the production phase which potentially provoke a decrease
      in the glutamate yield: Both the intracellular concentrations of glycolytic
      intermediates and the NADH/NAD ratio increase significantly during the period in
      which the overall metabolic rates decline. This correlates with the decrease in
      glutamate yield due in part to the production of lactate and also to the period
      of the fermentation in which growth no longer occurred.

PMID- 10937938
TI  - Use and limitations of modular metabolic control analysis in medicine and
      biotechnology.
AB  - By Metabolic Control Analysis (MCA), it has been shown that control on flux is in
      most cases shared by several enzymes rather than concentrated on one "rate
      limiting step." This analysis also allows the quantification of the control
      exerted by groups (modules) of enzymes. The modules may correspond to spatial
      compartments or to functional units. A brief outline of the modular approach to
      MCA is given. The criteria by which the system can be modularized and the concept
      of monofunctional unit are explained. Various studies in which control analysis
      was applied to biotechnological and medical issues are reviewed. In particular,
      MCA has turned out to be helpful in the assessment of the severity of enzyme
      deficiencies. Another application is the search for target enzymes or enzyme
      groups where pharmaceuticals can suppress the metabolism of pathogenic
      microorganisms most. In biotechnology, modular and "traditional" control analyses
      are valuable tools for choosing the most promising targets for genetic
      manipulation so as to increase a biosynthetic flux. As control coefficients are
      linear approximations, the effect of enhancing the activities of enzymes to a
      larger extent is often overestimated. Further limitations such as the restriction
      to stationary states, uncertainties due to spatial heterogeneities and the impact
      of experimental error are discussed.

PMID- 10937939
TI  - Metabolic modeling as a tool for evaluating polyhydroxyalkanoate copolymer
      production in plants.
AB  - The production of polyhydroxyalkanoates in plants is an interesting commercial
      prospect due to lower carbon feedstock costs and capital investments. The
      production of poly-(3-hydroxybutyrate) has already been successfully demonstrated
      in plant plastids, and the production of more complex polymers is under
      investigation. Using a mathematical simulation model this paper outlines the
      theoretical prospects of producing the copolymer poly-(3-hydroxybutyrate-co-3
      hydroxyvalerate) [P(3HB-3HV)] in plant plastids. The model suggests that both the
      3HV/3HB ratio and the copolymer production rate will vary considerably between
      dark and light conditions. Using metabolic control analysis we predict that the
      beta-ketothiolase predominately controls the copolymer production rate, but that
      the activity of all three enzymes influence the copolymer ratio. Dynamic
      simulations further suggest that controlled expression of the three enzymes at
      different levels may enable desirable changes in both the copolymer production
      rate and the 3HV/3HB ratio. Finally, we illustrate that natural variations in
      substrate and cofactor levels may have a considerable impact on both the
      production rate and the copolymer ratio, which must be taken into account when
      constructing a production system.

PMID- 10937940
TI  - Glutamate excretion as a major kinetic bottleneck for the thermally triggered
      production of glutamic acid by Corynebacterium glutamicum.
AB  - The study was aimed at evaluating the extent of flux control exercised by the
      amino acid excretion step on the glutamate production flux in C. glutamicum 2262
      strain that is induced for glutamate excretion by an upward temperature shift.
      Cells initially induced to excrete glutamate were cultivated at different
      controlled temperatures between 33 and 40 degrees C, and changes in glutamate
      excretion flux and intracellular concentration were determined in response to
      increased culture temperature. The fastest growth rate of 0.45 h(-1) and the
      lowest glutamate excretion rate of 1 mmole/g dw x h were observed at 33 degrees
      C, together with a high intracellular 0.5 mmole/g dw glutamate accumulation. On
      the contrary, the fastest glutamate excretion rate of 6 mmole/g dw x h was
      obtained at 40 degrees C, when cell growth was arrested and the internal
      glutamate level reduced to 0.25 mmol/g dw. The observed sixfold increase in
      excretion flux as a result of the temperature increase clearly suggests a
      specific effect of temperature on the glutamate export system which appears as
      the major kinetic bottleneck for the glutamate production flux. This conclusion
      is corroborated by the high internal accumulation of glutamate which, even under
      the fastest excretion conditions, severely inhibits the activity of the glutamate
      biosynthesis pathway.

PMID- 10937941
TI  - Mannuronan C-5-epimerases and their application for in vitro and in vivo design
      of new alginates useful in biotechnology.
AB  - The industrially important polysaccharide alginate is a linear copolymer of beta
      D-mannuronic acid (M) and alpha-L-guluronic acid (G). It is produced commercially
      by extraction from brown seaweeds, although some of the bacteria belonging to the
      genera Azotobacter and Pseudomonas also synthesize alginates. Alginates are
      synthesized as mannuronan, and varying amounts of the M residues in the polymer
      are then epimerized to G residues by mannuronan C-5-epimerases. The gel-forming,
      water-binding, and immunogenic properties of the polymer are dependent on the
      relative amount and sequence distribution of M and G residues. A family of seven
      calcium-dependent, secreted epimerases (AlgE1-7) from Azotobacter vinelandii have
      now been characterized, and in this paper the properties of all these enzymes are
      described. AlgE4 introduces alternating M and G residues into its substrate,
      while the remaining six enzymes introduce a mixture of continuous stretches of G
      residues and alternating sequences. Two of the enzymes, AlgE1 and AlgE3, are
      composed of two catalytically active domains, each introducing different G
      residue sequence patterns in alginate. These results indicate that the enzymes
      can be used for production of alginates with specialized properties.

PMID- 10937944
TI  - Partial left ventriculectomy: sunrise or sunset?
AB  - Partial left ventriculectomy (PLV) was proposed as an alternative to cardiac
      transplantation for patients with advanced heart failure. Patients with dilated
      cardiomyopathy that were considered eligible candidates for cardiac
      transplantation were offered the option of surgical ventriculectomy or to
      continue waiting for a donor organ. Sixty-two patients underwent PLV between May
      1996 and December 1998, mean age 54 years, 47 males, mean ejection fraction
      13.5%, mean peak oxygen consumption 10.8 ml/kg/min, 39% NYHA class III and 61%
      NYHA IV. Perioperative mortality 3.2%, 10/62 (16%) required implant of a left
      ventricular assist device (LVAD) due to shock, most in the early post-operative
      period. Survival at 1 and 2 years was 78% and 68%. Event free survival (freedom
      from death, LVAD, or return of NYHA class IV failure) was 50% and 37% at 1 and 2
      years. Event free survivors experienced improvement in NYHA class (3.7 to 2.2)
      and increased oxygen consumption (11.7 to 16.0 ml/kg/min). Based on these data
      PLV has a significant early failure rate and a 2 year event free survival rate of
      only 37%. PLV does not yield outcomes equivalent to cardiac transplantation based
      on current selection criteria and requires further investigation to determine its
      role in the treatment of advanced heart failure.

PMID- 10937943
TI  - How are cytokines activated in heart failure?
AB  - In the dilated and failing heart, elevated LV end-diastolic wall stress causes
      myocardial expression of cytokines, which directly or indirectly influence LV
      contractile performance and remodeling [22]. Due to poor diffusion of cytokines
      into the coronary effluent, the contribution of this myocardial production to the
      raised plasma levels is probably limited. Raised plasma levels of cytokines in
      heart failure are therefore more likely the result of extramyocardial production
      because of altered tissue perfusion and tissue hypoxia possibly modulated by
      bacterial endotoxin release from the gut.

PMID- 10937942
TI  - Flow cytometric analysis of metabolic stress effects due to recombinant plasmids
      and proteins in Escherichia coli production strains.
AB  - Overexpression of recombinant proteins in Escherichia coli often leads to a
      severe growth retardation of the host cells. Using flow cytometry, we analyzed
      the temporal development of the cellular content of DNA, total protein, and the
      recombinant product (human superoxide dismutase) in different strains. In cells
      carrying plasmids utilizing the phage T7 promoter 10 (pET vectors), induction
      with IPTG leads to an increase in protein content and size, an increase and a
      wide spreading of DNA content distribution, and a termination of cell division.
      These effects occurred with pET plasmids with or without an insert, but not with
      another plasmid which utilizes the tac promoter.

PMID- 10937945
TI  - Left ventricle assist systems: a possible alternative to heart transplantation
      for heart failure patients? Patient selection, techniques and benefit.

PMID- 10937946
TI  - Disorders of left ventricular structure and function in chronic uremia: how
      often, why and what to do with it?
AB  - Left ventricular (LV) structure and function abnormalities are frequent in
      individuals with chronic uraemia; these disorders are at increased risk of
      cardiovascular and overall morbidity and mortality in the pre-dialyzed
      population, during dialysis treatment and in renal transplant recipients. This
      review will attempt to summarize current knowledge of the prevalence,
      pathophysiological mechanisms of LV disease in chronic uraemia and to discuss
      useful medical strategies in this population.

PMID- 10937948
TI  - Familial dilated cardiomyopathy: clinical features in French families.
AB  - The aims of the study were to analyze the clinical features, the penetrance and
      the mode of inheritance of 13 French families with dilated cardiomyopathy using
      diagnostic criteria recently established by a European collaboration. METHODS:
      Screening consisted of physical examination, ECG and Echo of all the probands
      first degree relatives (n = 118). Using major Echo criteria [ejection fraction
      (EF) < 45% or FS < 25% and left ventricular diameter (LVD) > 117% of the
      predictive value], or combined minor Echo/ECG criteria, relatives were classified
      as affected, unknown or healthy. RESULTS: (1) Adult affected relatives (n = 31)
      were identified with major Echo criteria in 74% of cases, and with combined minor
      Echo/ECG criteria in 26% of cases. (2) In the unknown relatives (n = 21), the
      most common abnormality was an isolated left ventricular dilation (67%). (3) Mode
      of inheritance was autosomal dominant (AD) in 11 families and possibly autosomal
      recessive in two. (4) In AD families, the penetrance was incomplete in adults
      (72%), age-related (O.R.: 1.3 per 10 years; 95% CI 1.03-1.56) and sex-related
      [greater in men (87%) than in women (61%), actuarial survival curve: P<0.002].
      (5) Mortality related to end stage heart failure was 2.2 times as high as
      mortality related to sudden death (11% vs. 5%). CONCLUSIONS: (1) In the absence
      of a specific phenotype of FDC, the characterization of relatives appears more
      accurate when minor criteria were added. (2) Since high mortality (16%) and
      incomplete penetrance frequently give rise to small nuclei of clinically affected
      and alive relatives per family, the accurate model of penetrance that we proposed
      might be helpful in the future to enhance the statistical power of linkage
      analysis in this disease.

PMID- 10937949
TI  - Angiotensin-II type 1 receptor gene polymorphism and long-term survival in
      patients with idiopathic congestive heart failure.
AB  - BACKGROUND: It has been suggested that a genetic polymorphism in the angiotensin
      II type 1 receptor gene (ATRG) and the ACE gene DD genotype might have a
      synergistic influence on the risk of developing cardiovascular disease. AIMS: To
      study the possible interaction between polymorphisms in the ACE gene and the
      ATRG, regarding survival and left ventricular function. METHODS: Polymorphism of
      the two genes was studied in a population-based cohort of 194 patients with
      idiopathic heart failure, recruited from the western part of Sweden 1985-1988.
      The patients were investigated by echocardiography. The survival status was
      checked during the 7-year follow-up period. RESULTS: Although there was no
      statistically significant additive risk of the ATRG polymorphism, patients
      carrying the ACE gene DD genotype in combination with a C allele of the ATRG
      tended to have a poorer prognosis. DD +AA, OR 1.24 (95% CI 0.67-2.32, P = 0.49);
      DD +AC, OR 1.64 (95% CI 0.95-2.83, P = 0.08); DD + CC, OR 3.54 95% CI 0.78-16.1,
      P = 0.10); DD +AC/CC, OR 1.84 (95% CI 1.10-3.08, P = 0.02). Patients with the DD
      +AC/CC genotypes tended to have lower ejection fraction and increased left
      ventricular mass. CONCLUSIONS: There was a trend toward a worse prognosis in
      patients with the combination of a C-allele in the ATRG and the ACE gene DD
      genotype, suggesting an interaction of these two genetic polymorphisms on disease
      severity.

PMID- 10937947
TI  - Altered balance between matrix gelatinases (MMP-2 and MMP-9) and their tissue
      inhibitors in human dilated cardiomyopathy: potential role of MMP-9 in myosin
      heavy chain degradation.
AB  - BACKGROUND: End-stage of human dilated cardiomyopathy (DCM) is characterized by
      myocyte loss and fibrosis, and associated with ventricular dilatation and reduced
      cardiac function. Matrix metalloproteinases (MMPs) and their natural tissue
      inhibitors (TIMPs) have been involved in the myocardial remodeling. AIMS: To
      evaluate the potential role of matrix gelatinases (MMP-2 and MMP-9) in DCM, the
      balance between gelatinases and TIMPs and the gelatinase localization were
      investigated in left free wall ventricles from six normal donors and six patients
      with DCM at the transplantation time. METHODS: TIMP-(1, 2, 3 and 4) mRNAs were
      analyzed by quantitative reverse transcription-polymerase chain reaction (RT
      PCR). TIMP-1 and -2 protein content was assessed by ELISA. MMP-2 and MMP-9
      expression were examined by zymography and immunological techniques. RESULTS: All
      TIMPs were down-regulated in DCM hearts, especially TIMP-1 (reduced by 80%). Gel
      zymography revealed similar activity of MMP-2 and MMP-9 in both tissues. By in
      situ zymography and immunohistochemistry, active and immunoreactive gelatinases
      were pericardiomyocyte in control hearts and intracardiomyocyte in DCM hearts.
      Intracellular MMPs were associated with sarcomeric structure in DCM. To estimate
      a putative role of these gelatinases, several sarcomeric contractile proteins
      were digested in vitro by purified active MMP-9. Only myosin-heavy chain was
      cleaved in vitro giving 180-, 120-, 80- and 20-kDa proteolytic fragments. In
      vivo, two major myosin-heavy chain proteolytic fragments (80 and 20 kDa) were
      detected by specific monoclonal antibody against myosin-heavy chain in DCM left
      ventricular homogenates, only. CONCLUSIONS: Taken together, these data highly
      suggest that MMP-2 and MMP-9 may be involved in the disorganization of the
      contractile apparatus in DCM hearts.

PMID- 10937951
TI  - Monitoring patients with left ventricular failure by electrical impedance
      tomography.
AB  - Acute left ventricular failure (LVF) is a common medical emergency but detection
      and monitoring of pulmonary oedema remains problematic. Fluid is an important
      determinant of tissue impedance. Electrical impedance tomography (EIT) is a non
      invasive technique allowing localisation of impedance changes within tissue. We
      have investigated the relationship between LVF and the electrical impedance of
      lung tissue. Twenty patients with a clinical diagnosis of acute left ventricular
      failure were compared with 30 normal subjects. Patients were monitored using
      serial chest radiographs and electrical impedance tomography measurements of lung
      impedance during hospital admission. Radiographs were graded according to the
      severity of pulmonary oedema by two independent radiologists. Lung impedance was
      significantly (P<0.0001) lower than normal in patients with left ventricular
      failure. Values returned towards the normal range as LVF resolved. There was a
      similar improvement in the score of the chest radiographs. The electrical
      impedance of the lung is low in left ventricular failure and increases following
      treatment.

PMID- 10937950
TI  - Disruption of the relationship between renin and atrial natriuretic peptide early
      in the course of ventricular dysfunction.
AB  - BACKGROUND: Plasma renin activity is normal in left ventricular dysfunction in
      the absence of diuretic therapy. In health there is a reciprocal relationship
      between renin and atrial natriuretic peptide (ANP) but a positive correlation in
      advanced heart failure. The relationship between renin and ANP in mild left
      ventricular dysfunction is unknown. METHODS AND RESULTS: Patients with left
      ventricular dysfunction (n = 35, 18 without diuretic therapy) were compared to 20
      age-matched healthy subjects. Plasma concentrations of active renin (PARC), ANP
      and norepinephrine were measured after 20 min rest and 45 min after an infusion
      of normal saline (10 ml/kg body wt.). Basal plasma ANP was increased in patients
      with left ventricular dysfunction compared to healthy subjects, whether or not
      they were receiving diuretics. PARC was similar in healthy controls and patients
      untreated with diuretics but was increased in diuretic treated patients. After
      saline loading in healthy subjects PARC fell while ANP rose. Patients with left
      ventricular dysfunction had a smaller decline in PARC, that did not achieve
      statistical significance, but had a greater increase in plasma ANP compared to
      healthy subjects (P<0.05). The close reciprocal relationship between PARC and ANP
      observed in healthy subjects before and after saline loading (r = 0.8, P<0.001
      and r = 0.6, P<0.01) was weakened in those not receiving diuretics (r = 0.4,
      P<0.05 and r = 0.24, ns) and lost in those receiving diuretics (r = 0.1 and r =
      0.08). CONCLUSIONS: Patients with left ventricular dysfunction have a disturbance
      of the normal reciprocal relationship between PARC and ANP which antedates
      diuretic treatment. This should be taken into account when interpreting plasma
      neuroendocrine measurements in patients with ventricular dysfunction.

PMID- 10937953
TI  - Amlodipine reduces myocardial ischaemia during exercise without compromising left
      ventricular function in patients with silent ischaemia: a randomised, double
      blind, placebo-controlled study.
AB  - BACKGROUND: Left ventricular systolic function is reduced during episodes of
      silent ischaemia in patients with coronary artery disease (CAD). In most normal
      subjects left ventricular ejection fraction (LVEF) increases at least 5% during
      exercise whereas LVEF often remains unchanged or decreases in patients with CAD.
      The anti-ischaemic effect of calcium antagonists is well documented including a
      capability to reduce exercise-induced electrocardiographic ST-depressions,
      whereas the effect of these drugs on LV volume changes during exercise in
      patients with silent ischaemia is unknown. AIM: The aim of this study was to
      evaluate the effect of amlodipine on rest and exercise LVEF in patients with
      silent ischaemia. METHODS: Twenty-one patients completed a double-blind placebo
      controlled cross-over study. Conventional exercise test and radionuclide
      cardiographies during exercise were used for determining haemodynamic parameters.
      RESULTS: Exercise-induced electrocardiographic ST-depressions were reduced in 83%
      of the patients having ST-deviations during placebo even though 10 patients were
      already treated with a beta-blocker. Amlodipine did not affect left ventricular
      systolic function compared to placebo, neither at rest nor during exercise.
      CONCLUSION: The results indicated that amlodipine is a safe anti-ischaemic drug
      in patients with silent ischaemia concerning cardiac function.

PMID- 10937952
TI  - Haemodynamic, neurohumoral and exercise effects of losartan vs. captopril in
      chronic heart failure: results of an ELITE trial substudy. Evaluation of Losartan
      in the Elderly.
AB  - BACKGROUND: The AT1 receptor antagonists differ from the angiotensin converting
      enzyme inhibitors by achieving a more complete blockade of angiotensin II's
      actions and by not affecting bradykinin metabolism. There is little information
      on whether this causes clinically significant differences in haemodynamics,
      neurohormones and exercise tolerance in heart failure. AIMS: To compare the
      effects of losartan and captopril upon central and regional haemodynamics,
      neurohormones and exercise capacity in heart failure. METHODS: In a double-blind,
      randomised trial 18 patients aged > or =65 years with symptomatic heart failure
      were allocated to treatment with losartan (10 patients) or captopril (eight
      patients). Patients underwent assessment at baseline, after the first dose, at 12
      weeks and at 24 weeks. RESULTS: Systolic blood pressure fell by - 10.7% 1 h after
      captopril 6.25 mg (P = 0.007) and by - 4.8% 3 h after losartan 12.5 mg (P =
      0.02). The blood pressure reduction was sustained with losartan at 12 and 24
      weeks. Systemic vascular resistance fell acutely after captopril (-16.4%, P =
      0.01). Captopril caused an acute and sustained rise in superior mesenteric artery
      blood flow (+ 22.9%, P = 0.04), and a slower rise in renal artery blood flow
      (+31.7%, P = 0.01). Losartan had no acute effects on regional haemodynamics but
      had increased superior mesenteric artery blood flow by 38.1% at 12 weeks (P =
      0.02). There were no substantial differences between losartan and captopril, and
      no changes occurred in neurohormones or exercise capacity. CONCLUSION: No
      substantial differences were observed between losartan and captopril on central
      or regional haemodynamics, neurohormones or exercise capacity in elderly patients
      with stable symptomatic heart failure.

PMID- 10937955
TI  - Diagnostic tests, treatment and follow-up in heart failure patients--is there a
      gender bias in the coherence to guidelines?
AB  - AIMS: To relate clinical data in a consecutive cohort of patients admitted with
      heart failure in Sweden to demographic data and the use of diagnostic tests,
      medical treatment, care process and mortality. METHODS AND RESULTS: Retrospective
      investigation of all charts concerning patients discharged with primary diagnosis
      of heart failure in two Swedish hospitals during the second half of 1995 was
      undertaken. Records from 187 men and 192 women were analyzed, median age was 78
      years. During hospital stay 75% of the patients, regardless of gender, were
      examined with chest radiography. Echocardiography was performed in 59% of all
      patients, more often in men than in women (68% vs. 55%, P<0.011). The proportion
      of patients receiving ACE-inhibitors was higher if echocardiography had been
      performed, in both men (38% vs. 72%, P<0.001) and women (38% vs. 55%, P<0.033).
      Mean hospital stay was 6.4 days. After discharge 57% of the patients were
      referred to the general practitioners (GP), 21% to the hospital outpatient
      clinic. Young age (P<0.001), male gender (P<0.01) and treatment with beta
      blocking agents (P<0.035) were independently related to referral to hospital
      outpatient clinic. Within the group referred to the GPs, 62% of the patients had
      a follow-up visit within 3 months after discharge while 49% had visited the
      hospital outpatient clinic. The 1-year mortality rate was high, 30%. CONCLUSION:
      Patients admitted with heart failure in Sweden are old and carry a poor
      prognosis. In spite of the poor prognosis, only approximately half of the
      patients are followed-up within 3 months after discharge. There is, in contrast
      to practice guidelines, an underuse of diagnostic tests of left ventricular
      function and medical treatment is often suboptimal. These unsatisfactory findings
      were more pronounced in women.

PMID- 10937954
TI  - Neurohormonal reactivation in heart failure patients on chronic ACE inhibitor
      therapy: a longitudinal study.
AB  - BACKGROUND: Angiotensin Converting Enzyme inhibitors reduce mortality in heart
      failure. One therapeutic mechanism is believed to be the reduction of circulating
      angiotensin II and aldosterone. However, the Renin-Angiotensin-Aldosterone axis
      (RAAS) is not uniformly suppressed during therapy for heart failure. This effect
      has been referred to as 'angiotensin II reactivation' and 'aldosterone escape'
      and their reactivation may herald clinical deterioration. In the CONSENSUS I
      trial, correlations were seen between mortality, and angiotensin II and
      aldosterone. Furthermore, mortality was lower in those with good angiotensin II
      suppression. Therefore, neurohormonal elevation despite adequate treatment may
      associate with a poorer prognosis. AIMS: To follow chronic heart failure patients
      on ACE inhibitors for 18 months to assess whether or not angiotensin II and
      aldosterone reactivation are progressive with time, whether reactivation of both
      occurs simultaneously, and whether different ACE inhibitors have different
      neurohormonal profiles. METHODS AND RESULTS: We studied 22 patients (M/F 19:3,
      72.5+/-7 years) on stable ACE inhibitors. Five times, in 18 months, samples were
      taken for neurohormones and ACE activity. Mean levels of neurohormones were
      remarkably stable over time, although captopril takers had generally higher
      angiotensin II, but lower aldosterone and renin. Aldosterone 'escape' (> 80
      pg/ml) occurred in 13/97 samples (13.5%), in 5/22 (23%) individuals. Angiotensin
      II was elevated > or =10 pg/ml in 8/102 samples (8%), in 6/22 (27%) individuals.
      Four subjects had isolated angiotensin II reactivation, and three had aldosterone
      escape alone. On regression analyses between neurohormones in captopril takers
      there were significant correlations between; renin and angiotensin II (r = 0.62;
      P<0.02); angiotensin II and aldosterone (r = 0.6; P<0.02); and renin and
      aldosterone (r = 0.92; P<0.00001). CONCLUSION: In stable heart failure patients
      un-suppressed levels of angiotensin II and aldosterone occur despite therapy, but
      they are not necessarily progressive, nor simultaneous. Furthermore,
      contemporaneous serum ACE activity makes it unlikely the data presented reflects
      poor compliance. The results suggest that captopril takers may have different
      neurohormonal profiles, i.e. higher angiotensin II, and also better correlations
      between RAAS components, compared to longer acting preparations, although the
      numbers are small. Our data supports that of Swedberg et al. who showed
      reductions in both aldosterone and angiotensin II due to ACE inhibitor therapy,
      but no correlation between ACE activity and angiotensin II and only a limited
      correlation (r = 0.37) between angiotensin II and aldosterone. This suggests that
      the interaction between the components of the renin-angiotensin system is not
      simple and linear. The fact that each phenomenon appears to occur in isolation
      means that neurohormonal monitoring of individual could provide useful
      information to direct additional therapy. The RALES study has demonstrated
      reduced mortality from the addition of spironolactone to an ACE inhibitor
      emphasising the benefit of enhanced suppression of aldosterone in heart failure.
      Captopril may be less effective at suppressing the RAAS due to its short duration
      of action which would logically be associated with a more fluctuating pattern of
      ACE inhibition. In the presence of high levels of renin and angiotensin I even
      small differences in ACE activity will produce large variations in angiotensin II
      levels. Further studies should be directed at understanding the different
      mechanisms behind angiotensin II and aldosterone generation during ACE
      inhibition.

PMID- 10937956
TI  - Use of medical resources and quality of life of patients with chronic heart
      failure: a prospective survey in a large Italian community hospital.
AB  - AIMS: To assess the prevalence, clinical characteristics, use of medical
      resources and quality of life in consecutive patients with chronic heart failure
      (CHF) hospitalized in a large community hospital during 3 months. METHODS AND
      RESULTS: The study group included 354 patients with CHF, admitted in the
      Departments of Internal Medicine (97%) and Cardiology. Median age was 78 years
      [72;85], 45% were males. CHF was the main diagnosis in 72%; 28% were in NYHA
      class III and 49% in class IV; 42% had atrial fibrillation. The median hospital
      stay was 8 days [5;14], in-hospital mortality 9% in those admitted for CHF and
      19% in those admitted primarily for other diseases. Patients with CHF occupied
      15% of the beds; 1330 ECGs, 389 chest X-rays, 112 echocardiograms and 10 coronary
      angiograms were performed. A quality of life questionnaire revealed that 82% had
      problems with mobility, 54% with self-care and 88% with everyday activity. Thirty
      nine percent of patients had at least one hospitalization during the previous
      year. CONCLUSIONS: Ninety-seven percent of hospitalized patients with CHF are
      admitted in the Internal Medicine wards and occupy 15% of beds. The majority of
      the patients are 72 years or older, with severe heart failure. The frequency of
      rehospitalization(s) and mortality rate in this population remains high.
      Echocardiography is performed only in 27% of patients.

PMID- 10937957
TI  - Antithrombotic therapy in heart failure: a randomized comparison of warfarin vs.
      aspirin (HELAS).
AB  - It is uncertain whether anti-thrombotic treatment reduces the incidence of
      thrombo-embolism in patients with heart failure, so there is a need for a large
      scale controlled study to assess the effects of anti-thrombotic therapy in this
      setting. We report the design of a randomized controlled multicenter double blind
      trial examining the effects of aspirin, warfarin and placebo in patients with
      heart failure on the risk of thrombo-embolism. We planned to recruit 6000
      patients with heart failure without contraindications to anticoagulants or
      antiplatelet agents and to follow them for a mean time of 2 years following
      randomization. The study was planned to determine the rate of thrombo-embolic and
      haemorrhagic events and death among patients randomized to aspirin, warfarin and
      placebo, stratified according to the presence or absence of underlying coronary
      disease. Ancillary studies parallel to the main study will attempt to identify
      clinical and echocardiographic risk factors for thrombo-embolism and will also
      examine whether hemostatic or neurohormonal mechanisms contribute to an increase
      in the risk of thrombo-embolism in patients with heart failure. We hoped that the
      results of the study would improve the clinical management and cost-effectiveness
      of treatment for patients with heart failure. However, the recruitment of
      patients proved more difficult than expected and a number of centers decided not
      to participate. To avoid a great delay it was decided by the principal
      investigators and submitted to the executive committee to terminate enrolment in
      this study when 300 patients had been enrolled, and accept that this is a pilot
      study.

PMID- 10937959
TI  - Definition of heart failure.

PMID- 10937960
TI  - Self-organized hierarchical structure in a plastic network of chaotic units.
AB  - Formation of a layered structure is studied in a globally coupled map of chaotic
      units with a plastic coupling strength that changes depending on the states of
      units globally and an external input. In the parameter region characterized by
      weakly chaotic and desynchronized dynamics, units spontaneously form a
      hierarchical structure due to the influence of the input. This hierarchical
      structure is not fixed in time, and is successively reorganized. It is found that
      the distribution of lifetimes of the structure obeys a power law. The possible
      relevance of the present result to information processing in the brain is briefly
      discussed.

PMID- 10937962
TI  - Learning non-stationary conditional probability distributions.
AB  - While sophisticated neural networks and graphical models have been developed for
      predicting conditional probabilities in a non-stationary environment, major
      improvements in the training schemes are still required to make these approaches
      practically viable.

PMID- 10937961
TI  - Improving local minima of Hopfield networks with augmented Lagrange multipliers
      for large scale TSPs.

PMID- 10937963
TI  - The patchwork engine: image segmentation from shape symmetries.
AB  - We propose blind segmentation of images into shape-related 'patches' based on pre
      calculated local symmetries (Van Tonder, G.J. & Ejima, Y. (1999). (Forthcoming a)
      Flexible computation of shape symmetries. Submitted for publication) in shape
      boundary contours. First, lateral weights between all points in the boundary
      contour map are assigned analogous to Euclidean distance maps in watershed
      segmentation (Beucher, S. & Lantejoul, C. (1979). Use of watersheds in contour
      detection. Proceedings of the International Workshop on Image Processing, CCETT,
      Rennes, France.). Lateral weights are then used to: (1) extract local maxima in
      symmetries; (2) link maxima within locally enclosed boundary contours; and (3)
      reconstruct shape contours using symmetry maxima as 'seeds'. The new model
      overcomes weaknesses of watershed segmentation. The new model closes gaps in
      relatively more solid image contours, but it is fundamentally different from
      methods based on contour interpolation (Grossberg, S., Mingolla, E. & Todorovc,
      D. (1989). A neural network architecture for preattentive vision, IEEE
      Transactions on Biomedical Engineering 36, 65-84; Heitger, F. & von der Heydt, R.
      (1993). A computational model of neural contour processing: figure-ground
      segregation and illusory contours. Proceedings of the Fourth International
      Conference on Computer Vision, IEEE Computer Society Press, Washington D.C. (pp.
      32-40)). Images are segmented into shape-relevant color-by-number-like patches
      which compare well to related methods (Gauch, J. & Pizer, M. (1993). The
      intensity axis of symmetry and its application to image segmentation, IEEE
      Transactions on Pattern Analysis and Machine Intelligence, 15 (8), 753-770; Ilg,
      W. & Ogniewicz, R. (1995). The application of Voronoi skeletons to perceptual
      grouping in line images, Proceedings of the 11th International Conference on
      Pattern Recognition, The Hague, The Netherlands, pp. 382-385; Zhu, S.C. & Yuille,
      A.L. (1996) FORMS: a flexible object recognition and modeling system,
      International Journal of Computer Vision, 20 (3), 187-212.). Two primitive
      operations, comparison and merging of patches, are proposed as drives for
      exposing more global shape contours from patches. We conclude that symmetry goes
      beyond abstract shape morphology: it can contribute to figure-ground segmentation
      in early vision and form part of primitive operations needed to create hypotheses
      of complex shape.

PMID- 10937965
TI  - Local minima and plateaus in hierarchical structures of multilayer perceptrons.
AB  - Local minima and plateaus pose a serious problem in learning of neural networks.
      We investigate the hierarchical geometric structure of the parameter space of
      three-layer perceptrons in order to show the existence of local minima and
      plateaus. It is proved that a critical point of the model with H - 1 hidden units
      always gives many critical points of the model with H hidden units. These
      critical points consist of many lines in the parameter space, which can cause
      plateaus in learning of neural networks. Based on this result, we prove that a
      point in the critical lines corresponding to the global minimum of the smaller
      model can be a local minimum or a saddle point of the larger model. We give a
      necessary and sufficient condition for this, and show that this kind of local
      minima exist as a line segment if any. The results are universal in the sense
      that they do not require special properties of the target, loss functions and
      activation functions, but only use the hierarchical structure of the model.

PMID- 10937964
TI  - Position invariant recognition in the visual system with cluttered environments.
AB  - The effects of cluttered environments are investigated on the performance of a
      hierarchical multilayer model of invariant object recognition in the visual
      system (VisNet) that employs learning rules that utilise a trace of previous
      neural activity. This class of model relies on the spatio-temporal statistics of
      natural visual inputs to be able to associate together different exemplars of the
      same stimulus or object which will tend to occur in temporal proximity. In this
      paper the different exemplars of a stimulus are the same stimulus in different
      positions. First it is shown that if the stimuli have been learned previously
      against a plain background, then the stimuli can be correctly recognised even in
      environments with cluttered (e.g. natural) backgrounds which form complex scenes.
      Second it is shown that the functional architecture has difficulty in learning
      new objects if they are presented against cluttered backgrounds. It is suggested
      that processes such as the use of a high-resolution fovea, or attention, may be
      particularly useful in suppressing the effects of background noise and in
      segmenting objects from their background when new objects need to be learned.
      However, it is shown third that this problem may be ameliorated by the prior
      existence of stimulus tuned feature detecting neurons in the early layers of the
      VisNet, and that these feature detecting neurons may be set up through previous
      exposure to the relevant class of objects. Fourth we extend these results to
      partially occluded objects, showing that (in contrast with many artificial vision
      systems) correct recognition in this class of architecture can occur if the
      objects have been learned previously without occlusion.

PMID- 10937966
TI  - Learning in higher order Boltzmann machines using linear response.
AB  - We introduce an efficient method for learning and inference in higher order
      Boltzmann machines. The method is based on mean field theory with the linear
      response correction. We compute the correlations using the exact and the
      approximated method for a fully connected third order network of ten neurons. In
      addition, we compare the results of the exact and approximate learning algorithm.
      Finally we use the presented method to solve the shifter problem. We conclude
      that the linear response approximation gives good results as long as the
      couplings are not too large.

PMID- 10937967
TI  - A recurrent neural network for solving linear projection equations.
AB  - Linear projection equations arise in many optimization problems and have
      important applications in science and engineering. In this paper, we present a
      recurrent neural network for solving linear projection equations in real time.
      The proposed neural network has two layers and is amenable to parallel
      implementation with simple hardware. In the theoretical aspect, we prove that the
      proposed neural network can converge globally to the solution set of the problem
      when the matrix involved in the problem is positive semidefinite and can converge
      exponentially to a unique solution when the matrix is positive definite. In
      addition, we analyze the stability of the related dynamic system in detail. As an
      application, we show that the proposed neural network can be used directly to
      solve linear and convex quadratic programming problems and linear complementary
      problems with positive semidefinite matrices. The validity and transient behavior
      of the neural network are demonstrated by using three numerical examples.

PMID- 10937968
TI  - Efficient perceptron learning using constrained steepest descent.
AB  - An algorithm is proposed for training the single-layered perceptron. The
      algorithm follows successive steepest descent directions with respect to the
      perceptron cost function, taking care not to increase the number of misclassified
      patterns. The problem of finding these directions is stated as a quadratic
      programming task, to which a fast and effective solution is proposed. The
      resulting algorithm has no free parameters and therefore no heuristics are
      involved in its application. It is proved that the algorithm always converges in
      a finite number of steps. For linearly separable problems, it always finds a
      hyperplane that completely separates patterns belonging to different categories.
      Termination of the algorithm without separating all given patterns means that the
      presented set of patterns is indeed linearly inseparable. Thus the algorithm
      provides a natural criterion for linear separability. Compared to other state of
      the art algorithms, the proposed method exhibits substantially improved speed, as
      demonstrated in a number of demanding benchmark classification tasks.

PMID- 10937969
TI  - Information complexity of neural networks.
AB  - This paper studies the question of lower bounds on the number of neurons and
      examples necessary to program a given task into feed forward neural networks. We
      introduce the notion of information complexity of a network to complement that of
      neural complexity. Neural complexity deals with lower bounds for neural resources
      (numbers of neurons) needed by a network to perform a given task within a given
      tolerance. Information complexity measures lower bounds for the information (i.e.
      number of examples) needed about the desired input-output function. We study the
      interaction of the two complexities, and so lower bounds for the complexity of
      building and then programming feed-forward nets for given tasks. We show
      something unexpected a priori--the interaction of the two can be simply bounded,
      so that they can be studied essentially independently. We construct radial basis
      function (RBF) algorithms of order n3 that are information-optimal, and give
      example applications.

PMID- 10937970
TI  - A connectionist model for convex-hull of a planar set.
AB  - A neural network model is proposed for computation of the convex-hull of a finite
      planar set. The model is self-organizing in that it adapts itself to the hull
      vertices of the convex-hull in an orderly fashion without any supervision. The
      proposed network consists of three layers of processors. The bottom layer
      computes the activation functions, the outputs of which are passed onto the
      middle layer. The middle layer is used for winner selection. These information
      are passed onto the topmost layer as well as fed back to the bottom layer. The
      network in the topmost layer self-organizes by labeling the hull-processors in an
      orderly fashion so that the final convex-hull is obtained from the topmost layer.
      Time complexities of the proposed model are analyzed and are compared with
      existing models of similar nature.

PMID- 10937971
TI  - Multilayer neural networks for solving a class of partial differential equations.
AB  - In this paper, training the derivative of a feedforward neural network with the
      extended backpropagation algorithm is presented. The method is used to solve a
      class of first-order partial differential equations for input-to-state
      linearizable or approximate linearizable systems. The solution of the
      differential equation, together with the Lie derivatives, yields a change of
      coordinates. A feedback control law is then designed to keep the system in a
      desired behavior. The examination of the proposed method, through simulations,
      exhibits the advantages of it. They include easily and quickly finding
      approximate solutions for complicated first-order partial differential equations.
      Therefore, the work presented here can benefit the design of the class of
      nonlinear control systems, where the nontrivial solutions of the partial
      differential equations are difficult to find.

PMID- 10937972
TI  - Heart failure: why and how to define it?

PMID- 10937973
TI  - Primary care physicians: champions of or an impediment to optimal care of the
      patient with heart failure?

PMID- 10937974
TI  - Novel approaches to retard ventricular remodeling in heart failure.
AB  - While the etiologies of congestive heart failure (CHF) are diverse, a common
      event in the progression of this disease process is LV remodeling, increased wall
      stress, and subsequent pump dysfunction. Therapeutic approaches for CHF have been
      focused upon reducing LV afterload through vasodilator therapy, or by
      blocking/interrupting the effects of neurohormonal stimuli. However, another
      therapeutic approach would be to directly intervene in the LV remodeling process
      with CHF. An important determinant in the maintenance of myocyte shape, alignment
      and transduction of myocyte shortening into an overall ejection is the structural
      support provided by the fibrillar collagen matrix. As in most tissue remodeling
      processes, LV myocardial remodeling with CHF is accompanied by changes in the
      structure and composition of the collagen matrix. Matrix metalloproteinases
      (MMPs) are an endogenous family of zinc-dependent enzymes which have been
      identified to be responsible for matrix remodeling and alterations in MMP
      expression and activity have been identified in clinical and animal models of
      CHF. Moreover, alterations in the tissue inhibitors of MMPs (TIMPs) have also
      been identified to occur in the end-stage CHF myocardium. Thus, it is very likely
      that increased MMP activity and reduced inhibitory control of the TIMPs
      contribute to the LV remodeling process with CHF. A number of bioactive peptides
      and cytokines influence MMP and TIMP expression and activity. In addition,
      pharmacologically active MMP inhibitors have been synthesized and are currently
      under study. Accordingly, the control of MMP and TIMP expression and activity
      within the failing myocardium represents a new and potentially significant
      therapeutic target for CHF.

PMID- 10937975
TI  - Novel neuropeptides in the pathophysiology of heart failure: adrenomedullin and
      endothelin-1.
AB  - The clinical success of neurohumoral manipulation by ACE inhibitors and beta
      blockers in heart failure has led to new therapeutic approaches. New neurohumoral
      factors are now viewed as offering the potential for treatment interventions. Not
      only do we consider blocking the production of deleterious hormones, but also,
      more recently, consideration has been given to augmenting the actions of factors
      with potentially beneficial actions. Hopefully such manipulation of ADM and ET-1
      can result in further improvement in the well-being of heart failure patients.

PMID- 10937976
TI  - Is there a common mechanism of benefit for effective treatment of heart failure?

PMID- 10937977
TI  - The role of arrhythmias in the progression of heart failure.

PMID- 10937978
TI  - Sudden death in heart failure: vascular or electrical?

PMID- 10937979
TI  - Surgical alternatives to transplantation for treatment of heart failure.

PMID- 10937980
TI  - Relation of atrial natriuretic peptides to left ventricular systolic and
      diastolic function in heart failure.
AB  - BACKGROUND: Plasma concentrations of atrial natriuretic peptides are correlated
      with atrial pressures, as are left ventricular ejection fraction and left
      ventricular filling abnormalities. AIMS: This study investigated the relation of
      atrial natriuretic peptides to both left ventricular systolic and diastolic
      function in heart failure. METHODS: Plasma concentrations of atrial natriuretic
      peptide and N-terminal pro-atrial natriuretic peptide were measured in 63
      patients with chronic heart failure and left ventricular systolic dysfunction.
      According to Doppler transmitral flow measurements, 19 patients had a restrictive
      and 44 patients had a non-restrictive left ventricular filling pattern. RESULTS:
      Plasma concentrations of atrial natriuretic peptide and N-terminal pro-atrial
      natriuretic peptide were higher in patients with a restrictive filling pattern
      than in patients with a non-restrictive filling pattern (197 vs. 75 pmol/l,
      P<0.0001 and 1.14 vs. 0.45 nmol/l, P<0.0001). In univariate analysis, atrial
      natriuretic peptide and N-terminal pro-atrial natriuretic peptide correlated with
      deceleration time, E/A ratio and left ventricular ejection fraction. In
      multivariate analysis, both peptides appeared independently related to left
      ventricular ejection fraction and left ventricular filling pattern. CONCLUSION:
      In patients with chronic heart failure, atrial natriuretic peptides provide
      information on left ventricular systolic as well as diastolic function.

PMID- 10937981
TI  - Plasma brain natriuretic peptide--an independent predictor of cardiovascular
      mortality in acute heart failure.
AB  - PURPOSE: To examine the prognostic importance of both plasma atrial natriuretic
      and B-(brain natriuretic peptide) following an episode of acute heart failure.
      SUBJECTS AND METHODS: A prospective cohort of 91 patients admitted into hospital
      with acute heart failure were recruited. After initial in-hospital management
      plasma ANP and BNP levels were measured by radioimmunoassay, and echocardiography
      was performed on the same day. Patients were followed up for 12 months and the
      main outcome measure was cardiovascular death. RESULTS: Plasma ANP and BNP levels
      were significantly higher in patients who died of a cardiovascular cause within
      12 months (P<0.001 and P<0.0001, respectively) or at 1-month (P<0.05 and P<0.001)
      after recruitment. By Kaplan-Meier estimated life-table curves, patients with
      above median plasma ANP or BNP levels had significantly higher 1-year mortality
      (42.5% vs. 11.6%, both P<0.005). By multivariate Cox proportional hazard
      regression analysis, the plasma BNP level was the most important prognostic
      factor predicting mortality (chi2 = 18.3, P<0.0001), followed by age (chi2 =
      11.5, P<0.001). Other factors including ANP, left ventricular ejection fraction
      by M-mode echocardiography, pulmonary arterial pressure, sex, cause of heart
      failure as well as New York Heart Association class were not significant.
      CONCLUSION: A plasma BNP level has independent and at least short-term prognostic
      significance in patients admitted with acute heart failure. This non-invasive and
      readily available blood test should be considered for risk stratification in
      patients with acute heart failure.

PMID- 10937982
TI  - Placebo-controlled comparison of candoxatril, an orally active neutral
      endopeptidase inhibitor, and captopril in patients with chronic heart failure.
AB  - AIMS: To compare the effects on exercise capacity of the neutral endopeptidase
      inhibitor candoxatril, and the angiotensin converting enzyme inhibitor captopril,
      in patients with mild to moderate heart failure. METHODS: In this multi-centre
      double-blind placebo controlled study, 60 patients with NYHA Class I-III heart
      failure were randomised to candoxatril 200 mg b.d. (n = 22), captopril 25-50 mg
      b.d. (n = 23) or placebo (n = 15). Treadmill exercise tests were carried out
      weekly during a 5-week single-blind placebo run-in phase until a stable baseline
      was achieved, and repeated at 4 weekly intervals during the 12-week double-blind
      treatment phase. RESULTS: Nine patients withdrew from the study--four candoxatril
      and five captopril. The placebo-adjusted increase in exercise duration after 12
      weeks was 56 s (95% CI, -26 to +137 s; P = 0.12) with candoxatril and 37 s (-43
      to + 117 s; P = 0.29) with captopril. CONCLUSIONS: Both candoxatril and captopril
      were well tolerated and treadmill exercise duration appeared to increase during
      12 weeks of therapy but this did not achieve statistical significance. This study
      tentatively suggests that in patients with heart failure, neutral endopeptidase
      inhibition may provide similar symptomatic benefits to angiotensin converting
      enzyme inhibition.

PMID- 10937983
TI  - Baseline clinical characteristics of patients recruited into the assessment of
      treatment with lisinopril and survival study.
AB  - BACKGROUND: The beneficial effect of ACE inhibitors on mortality has been
      established in a series of trials. However, in clinical practice, ACE inhibitors
      are commonly administered in doses much lower than those shown to be effective in
      the landmark trials. AIMS: This report describes the baseline characteristics of
      the patients recruited into the ATLAS study by age and gender sub-groups.
      METHODS: The ATLAS study compared the effects of 'low' dose (2.5-5.0 mg/day) to
      'high' dose (32.5-35.0 mg/day) lisinopril in a double-blind study of 3164
      patients with moderate to severe heart failure and left ventricular ejection
      fraction < 30% during a mean follow-up period of 46 months. The primary end-point
      was all cause mortality and the principal secondary end-point a composite of all
      cause hospitalisation or all-cause mortality. RESULTS: Among patients with heart
      failure selected for the presence of left ventricular systolic function there
      were few differences among age groups or between genders. Older patients were not
      so heavy, were more likely to have ischaemic heart disease, hypertension and
      atrial fibrillation contributing to their heart failure and had a higher blood
      urea. Women were not so heavy as men. Age and gender had no major influence on
      mean ejection fraction or baseline treatment in the ATLAS study. CONCLUSIONS:
      Weight and renal function may alter the plasma concentration of any given dose of
      an ACE inhibitor. Potential interactions between dose of lisinopril, weight and
      renal function will be explored after the study is completed.

PMID- 10937984
TI  - Beta-blocker therapy in advanced heart failure: clinical characteristics and long
      term outcomes.
AB  - AIMS: To evaluate the clinical characteristics and long-term outcomes of advanced
      heart failure patients (NYHA Class IIIb-IV) receiving beta-blocker therapy vs.
      those patients not receiving beta-blockers at randomization in the FIRST trial, a
      randomized, double-blind, placebo-controlled trial of epoprostenol vs. usual care
      in advanced heart failure. METHODS AND RESULTS: The patient population consisted
      of 471 patients enrolled in FIRST with Class IIIb-IV heart failure, left
      ventricular ejection fraction (LVEF) of <30%, advanced hemodynamic abnormalities,
      and standard pharmacologic treatment of ACE-inhibitor, diuretics, and/or digoxin.
      The study cohort consisted of 448 patients not receiving beta-blockers and 23
      patients receiving beta-blockers at randomization for the FIRST trial. Patients
      in the beta-blocker group had decreased rates of any clinical event (P = 0.03),
      worsening heart failure (P = 0.001), and death or worsening heart failure (P =
      0.0008) than patients not receiving beta-blockers. After adjusting for
      prognostically important variables, the favorable effect of beta-blockers on
      worsening heart failure (P = 0.02) and death or worsening heart failure (P =
      0.02) persisted. CONCLUSION: Patients with advanced heart failure who receive
      beta-blocker therapy have a lower rate of hospitalization and are less likely to
      experience worsening heart failure or death at 6 months than patients who are not
      treated with beta-blockers. These observational data contribute to the growing
      body of data demonstrating a favorable effect of beta-blockers on clinical
      outcomes in heart failure.

PMID- 10937985
TI  - Achieving appropriate endpoints in heart failure trials: the PRIME-II protocol.
      The Second Perspective Randomised study of Ibopamine on Mortality and Efficacy.
AB  - Many clinical trials unintentionally include patients with a low risk of the
      trial endpoints. PRIME II (The Second Perspective Randomised study of Ibopamine
      on Mortality and Efficacy) was a large international randomised double blind
      trial comparing the addition of ibopamine or placebo to the therapy of patients
      with advanced heart failure. The trial was stopped prematurely because ibopamine
      was associated with an increased fatality rate, but the protocol achieved its
      objective of including high-risk patients. Here we describe the protocol details
      that enabled patients with the desired degree of risk to be included. We also
      amplify our definition of mode of death. The PRIME II protocol was designed with
      the intention that patients in the placebo group would have an annual fatality
      rate of 20%. Since the study was to be conducted in some 200 centres in 13
      European countries, the inclusion criteria had to be simple and flexible,
      allowing for different clinical practice. The inclusion criteria, together with
      the use of simple investigations (which did not have to include angiographic or
      radionuclide ventriculography) are described. The annual fatality rate in the
      placebo group was just over 20%. Six categories of mode of death were used, but
      while they were reasonably easy to apply they did not reveal the reason for the
      unexpected adverse effect of ibopamine. The inclusion and exclusion criteria used
      for PRIME II, and the definitions of mode of death, were effective. The PRIME II
      protocol can be used as a model for future heart failure studies.

PMID- 10937986
TI  - The WASH study (Warfarin/Aspirin Study in Heart failure) rationale, design and
      end-points.
AB  - BACKGROUND: Athero-thrombotic events are common among patients with heart failure
      but there is no evidence that anti-thrombotic therapy is safe or effective in
      this clinical setting. AIMS AND METHODS: The WASH study is a prospective,
      randomised, open-label, blinded-end-point pilot study comparing the outcome of
      management without anti-thrombotic therapy compared to treatment with aspirin or
      warfarin in three parallel arms in patients with chronic heart failure due to
      left ventricular systolic dysfunction. The primary aim of the study is to assess
      the feasibility of conducting a large study in which one-third of patients would
      be randomised to no anti-thrombotic therapy. The principal secondary aim of the
      study is to compare the effects of treatment on the combined end-point of death,
      non-fatal myocardial infarction and non-fatal stroke. RESULTS: 279 patients have
      been randomised and by study close there were 626 patient-years of follow-up. The
      majority of patients randomised had heart failure secondary to coronary artery
      disease. We expect to commence data analysis in early 1999 and report later in
      that year. CONCLUSIONS: This pilot study demonstrated that it is technically
      feasible to conduct a study that included a no anti-thrombotic treatment arm but
      that recruitment to such a study would be slow and costly. A large trial
      comparing the effects of aspirin, warfarin and clopidogrel in three separate
      groups without a placebo arm is now intended.

PMID- 10937987
TI  - Annotated references in epidemiology.
AB  - The burden that heart failure imposes on the health care systems of the developed
      world is substantial and increasing. This article reviews the world literature on
      the epidemiology of heart failure and discusses the key methodological issues for
      research in this field.

PMID- 10937988
TI  - Update of recent clinical trials in heart failure and myocardial infarction.
AB  - BACKGROUND: There are currently many on-going clinical trials assessing therapies
      for the treatment of patients with heart failure. AIMS: The purpose of this
      series of papers is to present concise summaries of current randomised trials in
      the field of heart failure and myocardial infarction (MI). METHODS: Data from
      large double-blind, placebo-controlled trials, which are on-going or have only
      recently been published, are given in a format allowing easy comparison. Where
      appropriate, data from smaller studies are included. RESULTS: Major studies which
      are examined in this issue include CIBIS II, MERIT-HF, RESOLVD, SPICE, VEST, MACH
      1, ATLAS, RALES, CIDS and CASH. These trials assess the efficacy and safety of
      beta-blocker, angiotensin-II-receptor blocker, positive inotropic agent, calcium
      antagonist, angiotensin-converting enzyme (ACE) inhibitor, aldosterone receptor
      blocker, and antiarrhythmic interventions in the treatment of heart failure.
      CONCLUSIONS: The presentation of data from these on-going trials should allow an
      up-to-date assessment, by physicians, of the most appropriate and effective
      treatment for patients with heart failure. It is evident that some therapies may
      play no further role in the treatment of heart failure, due to the increased risk
      of mortality associated with their administration, whilst others may convey
      significant benefits.

PMID- 10937989
TI  - The complete atomic structure of the large ribosomal subunit at 2.4 A resolution.
AB  - The large ribosomal subunit catalyzes peptide bond formation and binds
      initiation, termination, and elongation factors. We have determined the crystal
      structure of the large ribosomal subunit from Haloarcula marismortui at 2.4
      angstrom resolution, and it includes 2833 of the subunit's 3045 nucleotides and
      27 of its 31 proteins. The domains of its RNAs all have irregular shapes and fit
      together in the ribosome like the pieces of a three-dimensional jigsaw puzzle to
      form a large, monolithic structure. Proteins are abundant everywhere on its
      surface except in the active site where peptide bond formation occurs and where
      it contacts the small subunit. Most of the proteins stabilize the structure by
      interacting with several RNA domains, often using idiosyncratically folded
      extensions that reach into the subunit's interior.

PMID- 10937991
TI  - Magnetic vortex core observation in circular dots of permalloy
AB  - Spin structures of nanoscale magnetic dots are the subject of increasing
      scientific effort, as the confinement of spins imposed by the geometrical
      restrictions makes these structures comparable to some internal characteristic
      length scales of the magnet. For a vortex (a ferromagnetic dot with a curling
      magnetic structure), a spot of perpendicular magnetization has been theoretically
      predicted to exist at the center of the vortex. Experimental evidence for this
      magnetization spot is provided by magnetic force microscopy imaging of circular
      dots of permalloy (Ni(80)Fe(20)) 0.3 to 1 micrometer in diameter and 50
      nanometers thick.

PMID- 10937992
TI  - High-gain harmonic-generation free-electron laser
AB  - A high-gain harmonic-generation free-electron laser is demonstrated. Our approach
      uses a laser-seeded free-electron laser to produce amplified, longitudinally
      coherent, Fourier transform-limited output at a harmonic of the seed laser. A
      seed carbon dioxide laser at a wavelength of 10.6 micrometers produced saturated,
      amplified free-electron laser output at the second-harmonic wavelength, 5.3
      micrometers. The experiment verifies the theoretical foundation for the technique
      and prepares the way for the application of this technique in the vacuum
      ultraviolet region of the spectrum, with the ultimate goal of extending the
      approach to provide an intense, highly coherent source of hard x-rays.

PMID- 10937990
TI  - The structural basis of ribosome activity in peptide bond synthesis.
AB  - Using the atomic structures of the large ribosomal subunit from Haloarcula
      marismortui and its complexes with two substrate analogs, we establish that the
      ribosome is a ribozyme and address the catalytic properties of its all-RNA active
      site. Both substrate analogs are contacted exclusively by conserved ribosomal RNA
      (rRNA) residues from domain V of 23S rRNA; there are no protein side-chain atoms
      closer than about 18 angstroms to the peptide bond being synthesized. The
      mechanism of peptide bond synthesis appears to resemble the reverse of the
      acylation step in serine proteases, with the base of A2486 (A2451 in Escherichia
      coli) playing the same general base role as histidine-57 in chymotrypsin. The
      unusual pK(a) (where K(a) is the acid dissociation constant) required for A2486
      to perform this function may derive in part from its hydrogen bonding to G2482
      (G2447 in E. coli), which also interacts with a buried phosphate that could
      stabilize unusual tautomers of these two bases. The polypeptide exit tunnel is
      largely formed by RNA but has significant contributions from proteins L4, L22,
      and L39e, and its exit is encircled by proteins L19, L22, L23, L24, L29, and
      L31e.

PMID- 10937993
TI  - Ultrafast electron localization dynamics following photo-induced charge transfer
AB  - Molecular dynamics occurring in the earliest stages following photo-induced
      charge transfer were investigated. Femtosecond time-resolved absorption
      anisotropy measurements on [Ru(bpy)(3)](2+), where bpy is 2,2'-bipyridine, reveal
      a time dependence in nitrile solutions attributed to initial delocalization of
      the excited state over all three ligands followed by charge localization onto a
      single ligand. The localization process is proposed to be coupled to nondiffusive
      solvation dynamics. In contrast, measurements sampling population dynamics show
      spectral evolution associated with wave packet motion on the excited state
      surface that is independent of solvent. The results therefore reveal two
      important contributions to the evolution of charge transfer states in condensed
      phase, one that is strongly coupled to the surrounding environment and another
      that follows a potential internal to the molecule.

PMID- 10937995
TI  - Folds on Europa: implications for crustal cycling and accommodation of extension.
AB  - Regional-scale undulations with associated small-scale secondary structures are
      inferred to be folds on Jupiter's moon Europa. Formation is consistent with
      stresses from tidal deformation, potentially triggering compressional instability
      of a region of locally high thermal gradient. Folds may compensate for extension
      elsewhere on Europa and then relax away over time.

PMID- 10937994
TI  - O2 activation by nonheme iron complexes: A monomeric Fe(III)-Oxo complex derived
      from O2.
AB  - Iron species with terminal oxo ligands are implicated as key intermediates in
      several synthetic and biochemical catalytic cycles. However, there is a dearth of
      structural information regarding these types of complexes because their
      instability has precluded isolation under ambient conditions. The isolation and
      structural characterization of an iron(III) complex with a terminal oxo ligand,
      derived directly from dioxygen (O2), is reported. A stable structure resulted
      from placing the oxoiron unit within a synthetic cavity lined with hydrogen
      bonding groups. The cavity creates a microenvironment around the iron center that
      aids in regulating O2 activation and stabilizing the oxoiron unit. These cavities
      share properties with the active sites of metalloproteins, where function is
      correlated strongly with site structure.

PMID- 10937996
TI  - Pleistocene milestones on the out-of-Africa corridor at Gesher Benot Ya'aqov,
      israel.
AB  - The Acheulean site of Gesher Benot Ya'aqov in the Dead Sea Rift of Israel
      documents hominin movements and technological development on a corridor between
      Africa and Eurasia. New age data place the site at 780,000 years ago (oxygen
      isotope stage 19), considerably older than previous estimates. The archaeological
      data from the site portray strong affinities with African stone tool traditions.
      The findings also reflect adroit technical skills and in-depth planning
      abilities, more advanced and complex than those of earlier archaeological
      occurrences in the Levant.

PMID- 10937997
TI  - A single adenosine with a neutral pKa in the ribosomal peptidyl transferase
      center.
AB  - Biochemical and crystallographic evidence suggests that 23S ribosomal RNA (rRNA)
      is the catalyst of peptide bond formation. To explore the mechanism of this
      reaction, we screened for nucleotides in Escherichia coli 23S rRNA that may have
      a perturbed pKa (where Ka is the acid constant) based on the pH dependence of
      dimethylsulfate modification. A single universally conserved A (number 2451)
      within the central loop of domain V has a near neutral pKa of 7.6 +/- 0.2, which
      is about the same as that reported for the peptidyl transferase reaction. In vivo
      mutational analysis of this nucleotide indicates that it has an essential role in
      ribosomal function. These results are consistent with a mechanism wherein the
      nucleotide base of A2451 serves as a general acid base during peptide bond
      formation.

PMID- 10937998
TI  - Inhibition of adipogenesis by Wnt signaling.
AB  - Wnts are secreted signaling proteins that regulate developmental processes. Here
      we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch
      that governs adipogenesis. Wnt signaling maintains preadipocytes in an
      undifferentiated state through inhibition of the adipogenic transcription factors
      CCAAT/enhancer binding protein alpha (C/EBPalpha) and peroxisome proliferator-
      activated receptor gamma (PPARgamma). When Wnt signaling in preadipocytes is
      prevented by overexpression of Axin or dominant-negative TCF4, these cells
      differentiate into adipocytes. Disruption of Wnt signaling also causes
      transdifferentiation of myoblasts into adipocytes in vitro, highlighting the
      importance of this pathway not only in adipocyte differentiation but also in
      mesodermal cell fate determination.

PMID- 10937999
TI  - Calcium sensitivity of glutamate release in a calyx-type terminal.
AB  - Synaptic efficacy critically depends on the presynaptic intracellular calcium
      concentration ([Ca2+]i). We measured the calcium sensitivity of glutamate release
      in a rat auditory brainstem synapse by laser photolysis of caged calcium. A rise
      in [Ca2+]i to 1 micromolar readily evoked release. An increase to >30 micromolar
      depleted the releasable vesicle pool in <0.5 millisecond. A comparison with
      action potential-evoked release suggested that a brief increase of [Ca2+]i to
      approximately 10 micromolar would be sufficient to reproduce the physiological
      release pattern. Thus, the calcium sensitivity of release at this synapse is
      high, and the distinction between phasic and delayed release is less pronounced
      than previously thought.

PMID- 10938000
TI  - Uptake of glutamate into synaptic vesicles by an inorganic phosphate transporter.
AB  - Previous work has identified two families of proteins that transport classical
      neurotransmitters into synaptic vesicles, but the protein responsible for
      vesicular transport of the principal excitatory transmitter glutamate has
      remained unknown. We demonstrate that a protein that is unrelated to any known
      neurotransmitter transporters and that was previously suggested to mediate the
      Na(+)-dependent uptake of inorganic phosphate across the plasma membrane
      transports glutamate into synaptic vesicles. In addition, we show that this
      vesicular glutamate transporter, VGLUT1, exhibits a conductance for chloride that
      is blocked by glutamate.

PMID- 10938001
TI  - Electronic communication at arteriosclerosis, thrombosis, and vascular biology

PMID- 10938002
TI  - ApoE in atherosclerosis : a protein with multiple hats.

PMID- 10938003
TI  - Lipids, lipases, and obesity: does race matter?

PMID- 10938004
TI  - On the association of elevated tPA/PAI-1 complex and von Willebrand factor with
      recurrent myocardial infarction.

PMID- 10938005
TI  - Hepatic and extrahepatic scavenger receptors: function in relation to disease.

PMID- 10938006
TI  - Nitric oxide synthase in atherosclerosis and vascular injury: insights from
      experimental gene therapy.
AB  - Gene therapy aims to intervene in a disease process by transfer and expression of
      specific genes in a target tissue or organ. Cardiovascular gene therapy in humans
      remains in its infancy, but in the last decade, experimental gene transfer has
      emerged as a powerful biological tool to investigate the function of specific
      genes in vascular disease pathobiology. Nitric oxide synthases, the enzymes that
      produce nitric oxide, have received considerable attention as potential
      candidates for vascular gene therapy because nitric oxide has pleiotropic
      antiatherogenic actions in the vessel wall, and abnormalities in nitric oxide
      biology are apparent very early in the atherogenic process. In this article, we
      review the use of nitric oxide synthases in experimental vascular gene therapy
      and assess the utility of these approaches for investigating the role of nitric
      oxide in atherosclerosis and their potential for human gene therapy.

PMID- 10938007
TI  - Retinoids and arterial smooth muscle cells.

PMID- 10938008
TI  - Early effects of arterial hemodynamic conditions on human saphenous veins
      perfused ex vivo.
AB  - Exposure to the arterial hemodynamic environment is thought to be a potential
      trigger for the pathological remodeling of saphenous vein grafts. Using matched
      pairs of freshly isolated human saphenous vein, we analyzed the early effects of
      ex vivo hemodynamic conditions mimicking the venous (native) compared with
      arterial (graft) environment on the key components of vascular remodeling, ie,
      matrix metalloproteinase (MMP)-9 and MMP-2 and cell proliferation. Interestingly,
      we found that arterial conditions halved latent MMP-9 (50+/-11%, P=0.01) and MMP
      2 (44+/-6%, P=0.005) levels relative to matched vein pairs maintained ex vivo
      under venous perfusion for up to 3 days. Immunostaining supported decreased MMP
      levels in the innermost area of arterially perfused veins. Either decreased
      synthesis or increased posttranslational processing may decrease MMP zymogen
      levels. Biosynthetic radiolabeling showed that arterial perfusion actually
      increased MMP-9 and MMP-2 production. When we then examined potential pathways
      for MMP zymogen processing, we found that arterial conditions did not affect the
      expression of MT-MMP-1, a cell-associated MMP activator, but that they
      significantly increased the levels of superoxide, another MMP activator,
      suggesting redox-dependent MMP processing. Additional experiments indicated that
      increased superoxide under arterial conditions was due to diminished scavenging
      by decreased extracellular superoxide dismutase. Arterial perfusion also
      stimulated cell proliferation (by 220% to 750%) in the majority of vein segments
      investigated. Our observations support the hypothesis that arterial hemodynamic
      conditions stimulate early vein graft remodeling. Furthermore, physiological
      arterial flow may work to prevent pathological remodeling, particularly the
      formation of intimal hyperplasia, through rapid inactivation of secreted MMPs
      and, possibly, through preferential stimulation of cell proliferation in the
      outer layers of the vein wall.

PMID- 10938009
TI  - Periadventitial inducible nitric oxide synthase expression and intimal
      thickening.
AB  - Positioning a silicone collar around the rabbit carotid artery induces a smooth
      muscle cell-rich intimal thickening. We investigated the localization of
      inducible nitric oxide synthase (iNOS) during thickening of the intima, the
      effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL
      (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18
      hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for
      iNOS, including naive, sham-operated, and carotid arteries in which ox-LDL had
      been infused locally for 14 days. Furthermore, collars were connected to osmotic
      minipumps for local delivery (5 microL. h(-1), 14 days, n=12) of saline or the
      iNOS inhibitor L-N(6)-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the
      adventitia and the periadventitial granulation tissue of collared arteries, iNOS
      positive macrophages and T lymphocytes were present from 18 hours onward. The
      media and intima were negative for iNOS. Reverse transcription-polymerase chain
      reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local
      inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine
      staining. Ox-LDL-treated arteries, which had a thicker intima, showed a
      pronounced influx of macrophages and T lymphocytes in all layers of the vessel
      wall, accompanied by iNOS expression in a subpopulation of these cells. Our study
      indicates that iNOS was not induced in intimal thickenings predominantly
      consisting of smooth muscle cells. However, iNOS was expressed in
      (peri)adventitial tissue and counteracted the progression of intimal thickening.
      Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive
      macrophages and T lymphocytes in the vessel, but this could not prevent the
      progression of intimal thickening.

PMID- 10938010
TI  - Molecular characterization and localization of the NAD(P)H oxidase components
      gp91-phox and p22-phox in endothelial cells.
AB  - The production of reactive oxygen species (ROS) within endothelial cells may have
      several effects, including alterations in the activity of paracrine factors, gene
      expression, apoptosis, and cellular injury. Recent studies indicate that a
      phagocyte-type NAD(P)H oxidase is a major source of endothelial ROS. In contrast
      to the high-output phagocytic oxidase, the endothelial enzyme has much lower
      biochemical activity and a different substrate specificity (NADH>NADPH). In the
      present study, we (1) cloned and characterized the cDNA and predicted amino acid
      structures of the 2 major subunits of rat coronary microvascular endothelial cell
      NAD(P)H oxidase, gp91-phox and p22-phox; (2) undertook a detailed comparison with
      phagocytic NADPH oxidase sequences; and (3) studied the subcellular location of
      these subunits in endothelial cells. Although these studies revealed an overall
      high degree of homology (>90%) between the endothelial and phagocytic oxidase
      subunits, the endothelial gp91-phox sequence has potentially important
      differences in a putative NADPH-binding domain and in putative glycosylation
      sites. In addition, the subcellular location of the endothelial gp91-phox and p22
      phox subunits is significantly different from that reported for the neutrophil
      oxidase, in that they are predominantly intracellular and collocated in the
      vicinity of the endoplasmic reticulum. This first detailed characterization of
      gp91-phox and p22-phox structure and location in endothelial cells provides new
      data that may account, in part, for the differences in function between the
      phagocytic and endothelial NAD(P)H oxidases.

PMID- 10938011
TI  - Nov gene encodes adhesion factor for vascular smooth muscle cells and is
      dynamically regulated in response to vascular injury.
AB  - Nephroblastoma overexpressed (NOV) is a member of the CCN family (connective
      tissue growth factor, CYR61, and NOV) of proteins that are involved in regulating
      the proliferation, differentiation, and adhesion of a variety of cell types. We
      have examined the expression of the NOV: gene and NOV protein by vascular smooth
      muscle cells (VSMCs), in vitro and in vivo, and the effects of recombinant NOV on
      VSMCs. Rat aortic VSMCs were found to express NOV: mRNA and NOV protein in vitro
      and in vivo. NOV: expression in adult rat tissues was very high in the aorta and
      was detected only weakly in the brain and lung by Northern analysis (relative
      levels 33:3:1). During postnatal development (3 days to 12 weeks), the expression
      of NOV: was correlated with markers of the differentiated smooth muscle cell
      phenotype (smooth muscle myosin heavy chain and SM22 alpha). In the rat carotid
      artery balloon injury model, NOV: was detectable by in situ hybridization and was
      downregulated in the media of the injured artery compared with the uninjured
      artery at 7 and 14 days after injury. Expression in the developing intima was
      barely detectable at 7 days after injury except for strong expression at the
      luminal surface. At 14 days after injury, NOV: expression was substantially
      increased throughout the intima. In vitro studies of the function of NOV protein
      showed that it promoted VSMC adhesion via a mechanism that was divalent cation
      and Arg-Gly-Asp independent but that it did not modulate VSMC proliferation or
      phenotype. The strong expression and dynamic regulation of NOV: in the arterial
      wall, together with its ability to promote VSMC adhesion, suggest that it may be
      involved in homeostasis and repair.

PMID- 10938012
TI  - Pathogenicity of thermolabile methylenetetrahydrofolate reductase for vascular
      dementia.
AB  - Although the major biochemical abnormality due to methylenetetrahydrofolate
      reductase (MTHFR) deficiency is hyperhomocyst(e)inemia, its pathogenicity appears
      to involve more than homocysteine toxicity. In patients with severe MTHFR
      deficiency, a metabolite(s) other than hyperhomocyst(e)inemia also appears to be
      associated with its clinical manifestation in cerebrovascular disease. To
      elucidate the specific role of the TT genotype of MTHFR in the development of
      cerebral infarction with and without cognitive impairment, we determined the
      prevalence of hyperhomocyst(e)inemia and the C677T genotypes of MTHFR in 143
      patients with vascular dementia, 122 patients with cerebral infarction, and 217
      healthy subjects matched for age and sex. Prevalence of hyperhomocyst(e)inemia
      [homocyst(e)ine >/=15 micromol/L] was higher in cerebrovascular patients with or
      without dementia than in normal control subjects (42.6%, 20.5%, and 10.1%,
      respectively; P=0.001). In contrast, a higher frequency of MTHFR TT genotype was
      found only in demented patients compared with nondemented patients and healthy
      controls (25.2%, 9.8%, and 12.0%, respectively; P=0.01). When the study subjects
      were divided into normohomocyst(e)inemic and hyperhomocyst(e)inemic groups, the
      TT genotype was significantly associated with the risk for vascular dementia in
      the hyperhomocyst(e)inemic group (odds ratio 4.13, 95% CI 2.18 to 7.85; P=0.03)
      but not in the normohomocyst(e)inemic group. Demented patients with multiple
      infarcts had a higher frequency of TT genotype (odds ratio 3.13, 95% CI 2.23 to
      4.39; P=0.0007), whereas those with a single infarct did not (odds ratio 2.03,
      P=0.15). In contrast, there was no significant association of the TT genotype
      with multiple infarcts in hyperhomocyst(e)inemic stroke patients. Taken together,
      these findings indicate a possible role of MTHFR TT genotype combined with
      hyperhomocyst(e)inemia in the pathogenesis of vascular dementia. Similar to the
      relationship between homocystinuria due to severe MTHFR deficiency and severe
      cystathionine beta-synthase deficiency, the TT genotype of MTHFR in
      hyperhomocyst(e)inemic subjects is differentiated from the cases of the TT
      genotype without hyperhomocyst(e)inemia or hyperhomocyst(e)inemia without the TT
      genotype in the development of cerebrovascular disease.

PMID- 10938013
TI  - Progression of aortic calcification is associated with metacarpal bone loss
      during menopause: a population-based longitudinal study.
AB  - offerosclerosis and osteoporosis are major causes of morbidity and mortality in
      postmenopausal women and have been suggested to be associated. No study has
      examined whether progression of atherosclerotic calcification is associated with
      bone loss. In the present study, we examined progression of aortic calcification,
      diagnosed by radiographic detection of calcified deposits in the abdominal aorta,
      in relation to metacarpal bone loss, as assessed by metacarpal radiogrammetry,
      during menopause. Initially premenopausal women (n=236), aged 45 to 57 years at
      baseline, were followed for 9 years. We additionally assessed the cross-sectional
      association between the extent of aortic calcification and metacarpal bone mass
      and density in 720 postmenopausal women. Twenty-five percent of women going
      through menopause showed progression of aortic calcification. The average loss of
      metacarpal bone mass among women with progression of aortic calcification was 3.2
      mm(2), and their loss of metacarpal bone density was 7.2 mm(2) %, whereas in
      women without progression of aortic calcification, these losses were 2.0 mm(2)
      and 5.6 mm(2) %, respectively, adjusted for age and years of follow-up (P<0.05).
      Additional adjustment for age at menopause, body mass index, blood pressure,
      smoking, diabetes mellitus, and use of hormone replacement therapy, thiazide, and
      loop diuretics did not influence these results. In postmenopausal women, a graded
      inverse cross-sectional association between the extent of aortic calcification
      and metacarpal bone mass and density was found. In conclusion, our results
      indicate that progression of atherosclerotic calcification is associated with
      increased bone loss in women during menopause.

PMID- 10938014
TI  - Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in
      men and women: the Health, Risk Factors, Exercise Training, and Genetics
      (HERITAGE) family study.
AB  - Abdominal obesity is associated with numerous metabolic alterations, such as
      hypertriglyceridemia and low levels of high density lipoprotein (HDL)
      cholesterol. However, compared with abdominally obese white individuals,
      abdominally obese black individuals have been characterized by higher plasma HDL
      cholesterol levels, suggesting that the impact of abdominal fat accumulation on
      the lipoprotein-lipid profile may differ among ethnic groups. Therefore, we have
      compared the associations between body fatness, visceral adipose tissue (AT)
      accumulation, and metabolic risk variables in a sample of 247 white men and 240
      white women versus a sample of 93 black men and 143 black women. Although no
      difference in mean total body fatness was found between the 2 race groups, white
      men had higher levels of visceral AT than did black men (P<0.001). Despite the
      fact that black women had a greater body fat content than did white women, black
      women had levels of visceral AT that were similar to those of white women,
      suggesting a lower susceptibility to visceral obesity in black women. This lower
      accumulation of visceral AT in blacks was accompanied by significantly reduced
      apolipoprotein B concentrations and ratios of total cholesterol to HDL
      cholesterol as well as higher plasma HDL cholesterol levels (P<0.05) compared
      with those values in whites. Irrespective of sex, higher postheparin plasma
      hepatic lipase (HL) and lower lipoprotein lipase (LPL) activities were found in
      whites, resulting in an HL/LPL ratio that was twice as high in whites as in
      blacks (P<0.005). Although differences in lipoprotein-lipid levels were noted
      between whites and blacks, results from multiple regression analyses revealed
      that after control for morphometric and metabolic variables of the study (body
      fat mass, visceral AT, LPL, HL, and age), ethnicity had, per se, only a minor
      contribution to the variance in plasma lipoprotein levels. Thus, our results
      suggest that the higher plasma HDL cholesterol levels and the generally more
      cardioprotective plasma lipoprotein profile found in abdominally obese black
      versus white individuals are explained, at least to a certain extent, by a lower
      visceral AT deposition and a higher plasma LPL activity in black individuals.

PMID- 10938015
TI  - Low levels of extrahepatic nonmacrophage ApoE inhibit atherosclerosis without
      correcting hypercholesterolemia in ApoE-deficient mice.
AB  - The prevention of atherosclerosis by apolipoprotein E (apoE) is generally
      attributed to the removal of plasma lipoprotein remnant particles. We developed
      transgenic apoE-knockout mice expressing apoE specifically in the adrenal gland
      and found that only 3% of the wild-type plasma level of apoE was sufficient to
      normalize plasma cholesterol levels in the apoE-deficient mouse. As expected,
      mice expressing apoE at levels that correct hypercholesterolemia had almost no
      cholesteryl ester deposition in their aortas. In contrast, their nontransgenic
      siblings had significant atherosclerosis. Unexpectedly, we found that
      atherosclerosis was also reduced in 2 transgenic lines expressing too little apoE
      (<1% to 2% of wild type) to correct their hypercholesterolemia. Gel exclusion
      chromatographic profiles of plasma lipoproteins and the size distributions of
      lipoproteins with density <1.063 (low density and very low density lipoproteins),
      as determined by dynamic laser light scattering, were the same in mice expressing
      <2 microg/mL plasma apoE and their nontransgenic littermates. We conclude that
      the antiatherogenic action of low levels of plasma apoE is not due to the
      clearance of remnant lipoproteins. Thus, low levels of apoE provided
      systemically, but not made in the liver or in macrophages, can block
      atherogenesis in the vascular wall independently of normalizing the plasma
      concentration of atherogenic remnant lipoprotein particles.

PMID- 10938016
TI  - Short-term feeding of atherogenic diet to mice results in reduction of HDL and
      paraoxonase that may be mediated by an immune mechanism.
AB  - Short-term feeding (up to 7 days) of an atherogenic diet to C57BL/6 low density
      lipoprotein receptor-deficient mice did not result in decreased hepatic
      paraoxonase (PON) mRNA but caused a dramatic decrease in plasma PON activity and
      mass. The decreased activity and mass were temporally related to an increase in
      plasma and high density lipoprotein (HDL) lipid hydroperoxides and to a decrease
      in HDL cholesterol and native apolipoprotein A-I (apoA-I) and apolipoprotein A-II
      (apoA-II). As the native apoA-I protein disappeared from the circulation, higher
      molecular weight forms of apoA-I appeared, some of which contained epitopes
      recognized by an antibody (EO6) that recognizes oxidized phospholipids. After
      mice consumed an atherogenic diet for 1 or 3 days, switching the mice to a low
      fat chow diet for 3 days resulted in a return to baseline levels of lipid
      hydroperoxides but only a small return toward baseline for HDL cholesterol, with
      no significant increase in apoA-I mass or PON activity and mass. After mice
      consumed an atherogenic diet for 3 days, switching to the chow diet for 3 days
      did not significantly alter the high molecular weight forms of apoA-I or the
      signal generated by EO6. In marked contrast, after mice consumed an atherogenic
      diet for 7 days, switching to the chow diet for 3 days resulted in a dramatic
      increase in native apoA-I to baseline levels, with virtual disappearance of the
      high molecular weight forms of apoA-I, including the form recognized by EO6.
      After mice consumed an atherogenic diet for 7 days, switching to the chow diet
      for 3 days also resulted in significant increases in HDL cholesterol and PON mass
      and activity, although baseline levels were not reached. IgG and IgM antibodies
      were found to be associated with apoA-I in control animals, were minimally
      decreased after the 3-day atherogenic diet, were dramatically decreased after the
      7-day atherogenic diet, and returned to near or above baseline levels after a
      return to the chow diet for 3 days. We conclude that the atherogenic diet rapidly
      induces lipid hydroperoxide formation and apoA-I oxidation with the formation of
      high molecular weight forms of apoA-I. Concomitant with these changes in apoA-I
      levels, HDL cholesterol and PON activity and mass declined without changes in
      mRNA levels for apoA-I or PON, suggesting increased clearance of these altered
      HDL particles. We further conclude that between the third and seventh day of the
      atherogenic diet, an as-yet-unidentified mechanism for clearing the high
      molecular weight forms of apoA-I is induced and that this mechanism may be
      related to the clearance of immune complexes.

PMID- 10938017
TI  - Oxidized LDL-induced NF-kappa B activation and subsequent expression of
      proinflammatory genes are defective in monocyte-derived macrophages from CD36
      deficient patients.
AB  - -CD36 is 1 of the class B scavenger receptor expressed on monocytes, monocyte
      derived macrophages (Mphi), platelets, and adipocytes. In our previous studies,
      we reported that the uptake of oxidized low density lipoproteins (OxLDLs) is
      reduced by approximately 50% in Mphi from CD36-deficient patients compared with
      that in control subjects. Recently, we have shown that CD36 is highly expressed
      in human atherosclerotic aorta. Possibilities have been raised that besides the
      wide distribution and multifunctional characteristics of CD36, this molecule may
      also be involved in the mediation of intracellular signaling. The aim of the
      present study was to elucidate the role of CD36 in cytokine secretion and to
      investigate the CD36-mediated intracellular signaling stimulated by OxLDL. On
      addition of OxLDL or thrombospondin-1, the Mphi from CD36-deficient patients
      secreted significantly less amounts of tumor necrosis factor-alpha (TNF-alpha)
      and interleukin-1 beta (IL-1 beta) compared with those from controls. RNase
      protection assay with multiprobe template sets demonstrated that after incubation
      with OxLDL, the mRNAs of a variety of cytokines, including genes encoding IL-1Ra,
      IL-1beta, IL-6, TNF-alpha and -beta, and interferon (IFN)-gamma and -beta, were
      significantly lower in the Mphi of patients. The addition of antibody against
      CD36 attenuated this OxLDL-induced response in controls. We also observed a
      reduced response in nuclear factor-kappa B (NF-kappa B) activity in OxLDL
      stimulated Mphi from CD36-deficient patients. Unlike OxLDL, stimulation by
      lipopolysaccharide induced an increase in NF-kappa B activity in Mphi from CD36
      deficient patients, suggesting that lipopolysaccharide-mediated signaling was
      conserved. These results demonstrate that in addition to the reduced OxLDL uptake
      that we reported previously, CD36-deficient patients may also have an impaired
      response of OxLDL-induced NF-kappa B activation and subsequent cytokine
      expression.

PMID- 10938018
TI  - Low density lipoprotein receptor of macrophages facilitates atherosclerotic
      lesion formation in C57Bl/6 mice.
AB  - Macrophage-derived foam cells play an important role in the initiation and
      progression of atherosclerosis. To examine the role of the macrophage low density
      lipoprotein receptor (LDLr) in atherosclerotic lesion formation, bone marrow from
      LDLr knockout [LDLr(-/-)] mice was transplanted into irradiated wild-type C57Bl/6
      [LDLr(+/+)] mice. After 3 months on an atherogenic diet, C57Bl/6 mice,
      reconstituted with LDLr(-/-) bone marrow, showed a mean lesion area of 34.7 x
      10(3)+/-22.4 x 10(3) microm(2) compared with 100. 8 x 10(3)+/-33.0 x 10(3)
      microm(2) (P<0.001) in control C57Bl/6 mice that were transplanted with LDLr(+/+)
      bone marrow. There were no significant differences in total serum cholesterol,
      triglyceride levels, and lipoprotein profiles between the 2 groups. Histochemical
      analysis of macrophage LDLr expression in the atherosclerotic lesions indicated
      that C57Bl/6 mice, reconstituted with LDLr(+/+) bone marrow, showed extensive
      staining of the foam cells in the atherosclerotic lesions, whereas mice
      reconstituted with LDLr(-/-) bone marrow showed only a few LDLr-positive foam
      cells. In vitro, peritoneal macrophages isolated from wild-type C57Bl/6 mice
      were, respectively, 4.7- and 10.7-fold more effective in cell association and
      degradation of atherogenic (125)I-beta-very low density lipoprotein than were
      LDLr(-/-) peritoneal macrophages, establishing that the LDLr on macrophages is
      important for the interaction of macrophages with beta-very low density
      lipoprotein. It is concluded that the LDLr on macrophages can facilitate the
      development of atherosclerosis, possibly by mediating the uptake of atherogenic
      lipoproteins.

PMID- 10938019
TI  - Expression of class A scavenger receptor inhibits apoptosis of macrophages
      triggered by oxidized low density lipoprotein and oxysterol.
AB  - The class A macrophage scavenger receptor (MSR-A) is a multifunctional trimeric
      glycoprotein involved in innate immune response as well as the development of
      lipid-laden foam cells during atherosclerosis. The MSR ligand, oxidized low
      density lipoprotein (oxLDL), is known to be cytotoxic to macrophages and other
      cell types. This study examined whether MSR mediates or modulates oxLDL-induced
      apoptosis. Treatment with oxLDL and its cytotoxic oxysterol, 7-ketocholesterol (7
      KC), reduced viability and increased DNA fragmentation in human THP-1 cells,
      Chinese hamster ovary cells, and mouse peritoneal macrophages. However, cell
      death and DNA fragmentation were markedly diminished in the phorbol ester
      differentiated MSR-expressing THP-1 cells and Chinese hamster ovary cells, with
      stable expression of MSR-AI after cDNA transfection when exposed to the same
      concentrations of oxLDL and 7-KC. Moreover, treatment with oxLDL and 7-KC induced
      much greater death and DNA fragmentation in MSR-A-deficient peritoneal
      macrophages compared with wild-type macrophages. Thus, MSR-A does not act as a
      receptor responsible for the apoptotic effect of oxLDL, and instead, expression
      of this receptor confers resistance of macrophages to the apoptotic stimulation
      by oxLDL and its cytotoxic lipid component. These results suggest that by
      preventing apoptosis, MSR-A may contribute to the long-term survival of
      macrophages and macrophage-derived lipid-laden foam cells in atherosclerotic
      lesions.

PMID- 10938020
TI  - Polymerase chain reaction-based method for quantifying recruitment of monocytes
      to mouse atherosclerotic lesions in vivo: enhancement by tumor necrosis factor
      alpha and interleukin-1 beta.
AB  - The critical role of monocyte recruitment in atherogenesis has been appreciated
      for some time. However, until recently, there have been no sufficiently sensitive
      methods for measuring rates of monocyte recruitment to the arterial wall in vivo.
      We have developed a novel highly sensitive method, based on the polymerase chain
      reaction, for quantitatively tracking DNA-marked monocytes and have adapted it
      for use in mice. We use the uniquely male gene, SRY:, on the Y chromosome as a
      gene marker. We transfuse monocytes from a male donor into a congenic female
      mouse, euthanize the mouse after 24 to 48 hours, and then quantify the arterial
      uptake of monocytes by quantitative polymerase chain reaction. This study
      describes the techniques used and their sensitivity and reproducibility and
      demonstrates the approach by assessing the effects of cytokines. In control low
      density lipoprotein receptor-negative mice, monocyte recruitment decreased
      slightly but significantly as lesions progressed. Intraperitoneal injection of a
      combination of tumor necrosis factor-alpha and interleukin-1 beta more than
      doubled the rate of monocyte recruitment into developing lesions. However, the
      response to the cytokines was much greater in younger mice with less advanced
      lesions than in older animals with more advanced lesions.

PMID- 10938021
TI  - Common and rare ABCA1 variants affecting plasma HDL cholesterol.
AB  - Mutations in ABCA1, a member of the ATP-binding cassette family, have been shown
      to underlie Tangier disease (TD) and familial hypoalphalipoproteinemia (FHA),
      which are genetic disorders that are characterized by depressed concentrations of
      plasma high density lipoprotein (HDL) cholesterol. An important question is
      whether common variants within the coding sequence of ABCA1 can affect plasma HDL
      cholesterol in the general population. To address this issue, we developed a
      screening strategy to find common ABCA1 variants. This strategy involved long
      range amplification of genomic DNA by using coding sequences only, followed by
      deep sequencing into the introns. This method helped us to characterize a new set
      of amplification primers, which permitted amplification of virtually all of the
      coding sequence of ABCA1 and its intron-exon boundaries with a single DNA
      amplification program. With these new sequencing primers, we found 3 novel ABCA1
      mutations: a frameshift mutation (4570insA, A1484S-->X1492), a missense mutation
      (A986D) in a TD family, and a missense mutation (R170C) in aboriginal subjects
      with FHA. We also used these sequencing primers to characterize 4 novel common
      amino acid variants in ABCA1, in addition to 5 novel common silent variants. We
      tested for association of the ABCA1 I/M823 variant with plasma HDL cholesterol in
      Canadian Inuit and found that M823/M823 homozygotes had significantly higher
      plasma HDL cholesterol compared with subjects with the other genotypes. The
      results provide proof of principle of the effectiveness of this approach to
      identify both rare and common ABCA1 genomic variants and also suggest that common
      amino acid variation in ABCA1 is a determinant of plasma HDL cholesterol in the
      general population.

PMID- 10938022
TI  - ApoE polymorphism and fish oil supplementation in subjects with an atherogenic
      lipoprotein phenotype.
AB  - The study assessed the efficacy of fish oil supplementation in counteracting the
      classic dyslipidemia of the atherogenic lipoprotein phenotype (ALP). In addition,
      the impact of the common apolipoprotein E (apoE) polymorphism on the fasting and
      postprandial lipid profile and on responsiveness to the dietary intervention was
      established. Fifty-five ALP males (aged 34 to 69 years, body mass index 22 to 35
      kg/m(2), triglyceride [TG] levels 1.5 to 4.0 mmol/L, high density lipoprotein
      cholesterol [HDL-C] <1.1 mmol/l, and percent low density lipoprotein [LDL]-3 >40%
      total LDL) completed a randomized placebo-controlled crossover trial of fish oil
      (3.0 g eicosapentaenoic acid/docosahexaenoic acid per day) and placebo (olive
      oil) capsules with the 6-week treatment arms separated by a 12-week washout
      period. In addition to fasting blood samples, at the end of each intervention
      arm, a postprandial assessment of lipid metabolism was carried out. Fish oil
      supplementation resulted in a reduction in fasting TG level of 35% (P<0.001), in
      postprandial TG response of 26% (TG area under the curve, P<0.001), and in
      percent LDL-3 of 26% (P<0.05). However, no change in HDL-C levels was evident
      (P=0.752). ANCOVA showed that baseline HDL-C levels were significantly lower in
      apoE4 carriers (P=0.035). The apoE genotype also had a striking impact on lipid
      responses to fish oil intervention. Individuals with an apoE2 allele displayed a
      marked reduction in postprandial incremental TG response (TG incremental area
      under the curve, P=0.023) and a trend toward an increase in lipoprotein lipase
      activity relative to non-E2 carriers. In apoE4 individuals, a significant
      increase in total cholesterol and a trend toward a reduction in HDL-C relative to
      the common homozygous E3/E3 profile was evident. Our data demonstrate the
      efficacy of fish oil fatty acids in counteracting the proatherogenic lipid
      profile of the ALP but also that the apoE genotype influences responsiveness to
      this dietary treatment.

PMID- 10938023
TI  - Associations of coronary heart disease risk factors with the intermediate lesion
      of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis
      in Youth (PDAY) Research Group.
AB  - The raised fatty streak (fatty plaque) is the gross term for the lesion
      intermediate between the juvenile (flat) fatty streak and the raised lesion of
      atherosclerosis. We measured the percentage of intimal surface involved with flat
      fatty streaks, raised fatty streaks, and raised lesions in the aortas and right
      coronary arteries of 2876 autopsied persons aged 15 through 34 years who died of
      external causes. Raised fatty streaks were present in the abdominal aortas of
      approximately 20% of 15- to 19-year-old subjects, and this percentage increased
      to approximately 40% for 30- to 34-year-old subjects. Raised fatty streaks were
      present in the right coronary arteries of approximately 10% of 15- to 19-year-old
      subjects, and this percentage increased to approximately 30% for 30- to 34-year
      old subjects. The percent intimal surface involved with raised fatty streaks
      increased with age in both arteries and was associated with high non-high density
      lipoprotein (HDL) and low HDL cholesterol concentrations in the abdominal aorta
      and right coronary artery, with hypertension in the abdominal aorta, with obesity
      in the right coronary artery of men, and with impaired glucose tolerance in the
      right coronary artery. Associations of risk factors with raised fatty streaks
      became evident in subjects in their late teens, whereas associations of risk
      factors with raised lesions became evident in subjects aged >25 years. These
      results are consistent with the putative transitional role of raised fatty
      streaks and show that coronary heart disease risk factors accelerate
      atherogenesis in the second decade of life. Thus, long-range prevention of
      atherosclerosis should begin in childhood or adolescence.

PMID- 10938024
TI  - Blood pressure, LDL cholesterol, and intima-media thickness: a test of the
      "response to injury" hypothesis of atherosclerosis.
AB  - The "response to injury" hypothesis is a plausible model of the development of
      atherosclerosis supported by observations from animal models. The present study
      uses epidemiological data to investigate the hypothesis that wall damage due to
      hypertension is a precursor of low density lipoprotein cholesterol (LDL-C)
      mediated atherosclerosis. The Los Angeles Atherosclerosis Study is following a
      cohort of 576 participants who were aged 40 to 60 years and were free of
      symptomatic cardiovascular disease at recruitment. Common carotid artery intima
      media thickness (IMT) was assessed by B-mode ultrasonography. After exclusion for
      nonfasting blood draw and other missing data, 511 subjects were available for
      analysis. IMT was regressed on LDL-C within tertiles of systolic blood pressure
      (SBP): low (93 to 122 mm Hg), middle (123 to 132 mm Hg), and high (133 to 175 mm
      Hg). Covariates were age, sex, body height, body mass index, ethnicity, smoking
      status, diabetes, and pharmacological treatment for hypertension or
      hypercholesterolemia. IMT was significantly related to LDL-C in the high SBP
      group (beta=0.025+/-0.008, where beta values are IMT [mm]/LDL-C [mmol/L];
      P=0.002) but not in the middle (beta=-0.006+/-0.008, P=0.39) or low (beta=
      0.004+/-0.009, P=0.64) SBP group. The slope in the high SBP group was
      significantly greater than in the middle (P=0.004) or low (P=0.014) SBP group.
      Results were similar for women and men, and after the exclusion of diabetics and
      persons using antihypertensive or lipid-lowering medications. Elevated LDL-C was
      associated with increased IMT in the upper tertile of SBP but not in the lower
      tertiles. These findings are consistent with the hypothesis that wall injury due
      to elevated SBP increases the susceptibility of the artery wall to LDL-C-mediated
      atherogenesis.

PMID- 10938025
TI  - Modification of protein moiety of human low density lipoprotein by hypochlorite
      generates strong platelet agonist.
AB  - Conflicting reports exist about the effects of mildly or extensively oxidized low
      density lipoproteins (LDLs) on the reactivity of human platelets. This platelet
      response is mainly caused by modification of the protein and lipid moiety, giving
      rise to very differently modified species with hardly predictable properties. The
      aim of this study was to prepare oxidized LDL with modifications essentially
      restricted to the protein moiety and to determine the eventual platelet
      responses. We treated LDL at 0 degrees C for 10 minutes with a 60- to 1000-fold
      molar excess of sodium hypochlorite in borate buffer in the presence of the
      radical scavenger butylated hydroxytoluene. Under these conditions, neither
      fragmentation of apolipoprotein B-100 nor formation of LDL aggregates was
      observed, and lipid oxidation products did not exceed the amount present in
      untreated LDLs. The degree of modification and the respective effects on platelet
      function were highly reproducible. Hypochlorite-modified LDLs act as strong
      platelet agonists, inducing morphological changes, dense granule release, and
      irreversible platelet aggregation. The evoked platelet effects are completely
      suppressed by inhibitors of the phosphoinositide cycle but not by EDTA or
      acetylsalicylic acid. Most likely, these effects are transmitted via high
      affinity binding to a single class of sites, which does not recognize native or
      acetylated LDL. Obviously, modified lysines, and the secondary lipid
      modifications derived from them, are not essential for this interaction. We
      conclude that bioactive oxidized lipids are not directly involved in the
      stimulation of platelets by hypochlorite-modified LDLs.

PMID- 10938026
TI  - Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1
      complex and von Willebrand factor are significant risk markers for recurrent
      myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study.
AB  - An impaired fibrinolytic function due to elevated plasma levels of plasminogen
      activator inhibitor (PAI)-1 activity or tissue plasminogen activator (tPA)
      antigen is correlated with the development of myocardial infarction (MI) in
      patients with manifest coronary heart disease. Recently, methods for determining
      the specific tPA/inhibitor complexes constituting tPA antigen in plasma have
      become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86
      of 1212 MI patients, subjected to blood sampling in a metabolically stable
      period, suffered reinfarction before the end of 1996. These individuals have been
      compared with an approximately equal number of matched MI patients without
      recurrence and a group of matched healthy control subjects regarding the plasma
      concentrations of some hemostatic factors. The hemostatic compounds studied
      (fibrinogen, von Willebrand factor, tPA antigen, PAI-1, and the tPA/PAI-1
      complex) were typically higher in the groups (men and women) with recurrence of
      MI compared with those without. The plasma concentrations were also typically
      higher in the pooled groups of patients compared with the groups of healthy
      control subjects. The largest between-group differences were found for the plasma
      tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher
      concentration (>/=75th percentile among the control subjects) of tPA/PAI-1 was
      1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for von Willebrand
      factor was 2.3 (1. 3 to 4.0). The tPA/PAI-1 complex correlated strongly with PAI
      1 and tPA antigen in all groups and with serum triglycerides and body mass index
      in all groups except for women with reinfarction. An increased plasma level of
      tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most
      likely, increased plasma levels of tPA/PAI-1 complex reflect impaired
      fibrinolysis, because the correlation with PAI-1 is strong. Further support is
      obtained indicating that the plasma concentration of von Willebrand factor is
      also an important risk marker for recurrent MI.

PMID- 10938027
TI  - Functional effects of the ABO locus polymorphism on plasma levels of von
      Willebrand factor, factor VIII, and activated partial thromboplastin time.
AB  - Lower levels of factor VIII and von Willebrand factor (vWF) have been reported in
      individuals with blood type O compared with individuals with other ABO blood
      types. However, this relationship has been demonstrated only by association
      studies and not by linkage studies. Also, it is not clear whether the ABO locus
      exerts a functional effect directly on these plasma factors or whether the ABO
      locus is in linkage disequilibrium with another locus that controls these
      factors. To distinguish between these 2 possibilities, we applied new statistical
      methods combining linkage and association tests in a pedigree-based sample. In
      contrast to most previous studies that used the ABO phenotypes, our study used
      the ABO genotypes, permitting us to distinguish AO from AA and BO from BB. Our
      results clearly showed significant linkage between the ABO locus and vWF antigen
      (P=0.00075). In addition, factor VIII coagulant activity and activated partial
      thromboplastin time showed suggestive linkage with the ABO locus (P=0.10 and
      P=0.13). All 3 plasma phenotypes showed significant differences between OO and
      non-OO genotypes. In addition, vWF antigen exhibited significant differences
      between O heterozygotes and non-OO homozygotes. This study is unique because it
      used a combined linkage and association test, which indicated that the ABO locus
      itself has a functional effect on these plasma phenotypes.

PMID- 10938028
TI  - Site-specific antiatherogenic effect of probucol in apolipoprotein E-deficient
      mice
AB  - -The lipid-lowering antioxidant probucol can inhibit atherosclerosis in animals
      and restenosis in humans. However, probucol has been shown to promote
      atherosclerosis in the aortic root of apolipoprotein E-deficient (apoE-/-) mice.
      In the current study, we examined the effects of probucol on both lesion
      formation at 4 sites along the aorta and lipoprotein oxidation in the plasma and
      aortas of apoE-/- mice receiving a diet containing 21.2% (wt/wt) fat and 0. 15%
      (wt/wt) cholesterol without or with 1% (wt/wt) probucol. After 6 months, controls
      had developed lesions at all sites investigated. Lesion development was strongly
      (P=0.0001) affected by probucol, but this effect was not uniform: lesion size was
      increased in the aortic root but significantly decreased in the arch, the
      descending thoracic aorta, and proximal abdominal aorta. Plasma and aortas of
      probucol-treated mice contained high concentrations of probucol and its
      metabolites (bisphenol and diphenoquinone); increased vitamin C; markedly
      decreased very low density lipoprotein (but not low density lipoprotein and high
      density lipoprotein); and decreased cholesterol, cholesteryl esters,
      triglycerides, vitamin E, and oxidized lipids compared with controls.
      Interestingly, probucol treatment did not decrease the proportion of aortic
      lipids that were oxidized. Plasma vitamin C and bisphenol, but not probucol,
      protected plasma lipids from ex vivo oxidation by peroxyl radicals. These results
      show that as in other species, probucol can inhibit lesion formation in most
      parts of the aorta of apoE-/- mice. This effect may involve lipid oxidation
      independent mechanisms localized within the vessel wall as well as lipid
      lowering.

PMID- 10938029
TI  - Will intermediate care be the undoing of the NHS?

PMID- 10938030
TI  - Controlling glucose and blood pressure in type 2 diabetes.

PMID- 10938031
TI  - Herbal medicines: where is the evidence?

PMID- 10938032
TI  - The increasing use of peripheral bone densitometry.

PMID- 10938033
TI  - Cheating at medical school.

PMID- 10938034
TI  - Israeli surgeons implant first permanent artificial ventricle.

PMID- 10938036
TI  - Gene therapy can reduce tumours

PMID- 10938035
TI  - Cost effectiveness of multiple sclerosis drugs remains unknown.

PMID- 10938037
TI  - Folic acid researchers honoured.

PMID- 10938038
TI  - In brief

PMID- 10938039
TI  - Health watchdog criticises NHS helpline.

PMID- 10938041
TI  - Study questions ethics of covert medication

PMID- 10938040
TI  - Sildenafil may help diabetic patients

PMID- 10938042
TI  - Canadian prisoners strike over smoking ban.

PMID- 10938043
TI  - Indian agency admits publishing "wrong" HIV figures.

PMID- 10938044
TI  - Spanish women to sue over breast implants.

PMID- 10938045
TI  - India struggles to meet polio deadline.

PMID- 10938046
TI  - Huntington's centre faces closure.

PMID- 10938047
TI  - Research finds high hepatitis B rate in indian island tribes

PMID- 10938048
TI  - Association of glycaemia with macrovascular and microvascular complications of
      type 2 diabetes (UKPDS 35): prospective observational study.
AB  - OBJECTIVE: To determine the relation between exposure to glycaemia over time and
      the risk of macrovascular or microvascular complications in patients with type 2
      diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital based
      clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4585 white,
      Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to
      treatment, were included in analyses of incidence; of these, 3642 were included
      in analyses of relative risk. OUTCOME MEASURES: Primary predefined aggregate
      clinical outcomes: any end point or deaths related to diabetes and all cause
      mortality. Secondary aggregate outcomes: myocardial infarction, stroke,
      amputation (including death from peripheral vascular disease), and microvascular
      disease (predominantly retinal photo-coagulation). Single end points: non-fatal
      heart failure and cataract extraction. Risk reduction associated with a 1%
      reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis
      of diabetes. RESULTS: The incidence of clinical complications was significantly
      associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was
      associated with reductions in risk of 21% for any end point related to diabetes
      (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to
      diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%,
      P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No
      threshold of risk was observed for any end point. CONCLUSIONS: In patients with
      type 2 diabetes the risk of diabetic complications was strongly associated with
      previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of
      complications, with the lowest risk being in those with HbA(1c) values in the
      normal range (<6.0%).

PMID- 10938050
TI  - Influence of maternal age at delivery and birth order on risk of type 1 diabetes
      in childhood: prospective population based family study. Bart's-Oxford Family
      Study Group.
AB  - OBJECTIVES: To examine the influence of parental age at delivery and birth order
      on subsequent risk of childhood diabetes. DESIGN: Prospective population based
      family study. SETTING: Area formerly administered by the Oxford Regional Health
      Authority. PARTICIPANTS: 1375 families in which one child or more had diabetes.
      Of 3221 offspring, 1431 had diabetes (median age at diagnosis 10.5 years, range
      0.4-28.5) and 1790 remained non-diabetic at a median age of 16. 1 years. MAIN
      OUTCOME MEASURES: Disease free survival and hazard ratios for the development of
      type 1 diabetes in all offspring, assessed by Cox proportional hazard regression.
      RESULTS: Maternal age at delivery was strongly related to risk of type 1 diabetes
      in the offspring; risk increased by 25% (95% confidence interval 17% to 34%) for
      each five year band of maternal age, so that maternal age at delivery of 45 years
      or more was associated with a relative risk of 3.11 (2.07 to 4.66) compared with
      a maternal age of less than 20 years. Paternal age was also associated with a 9%
      (3% to 16%) increase for each five year increase in paternal age. The relative
      risk of diabetes, adjusted for parental age at delivery and sex of offspring,
      decreased with increasing birth order; the overall effect was a 15% risk
      reduction (10% to 21%) per child born. CONCLUSIONS: A strong association was
      found between increasing maternal age at delivery and risk of diabetes in the
      child. Risk was highest in firstborn children and decreased progressively with
      higher birth order. The fetal environment seems to have a strong influence on
      risk of type 1 diabetes in the child. The increase in maternal age at delivery in
      the United Kingdom over the past two decades could partly account for the
      increase in incidence of childhood diabetes over this period.

PMID- 10938051
TI  - Th1 and Th2 responses: what are they?

PMID- 10938049
TI  - Association of systolic blood pressure with macrovascular and microvascular
      complications of type 2 diabetes (UKPDS 36): prospective observational study.
AB  - OBJECTIVE: To determine the relation between systolic blood pressure over time
      and the risk of macrovascular or microvascular complications in patients with
      type 2 diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital
      based clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4801
      white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not
      to treatment, were included in analyses of incidence; of these, 3642 were
      included in analyses of relative risk. OUTCOME MEASURES: Primary predefined
      aggregate clinical outcomes: any complications or deaths related to diabetes and
      all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke,
      lower extremity amputation (including death from peripheral vascular disease),
      and microvascular disease (predominantly retinal photocoagulation). Single end
      points: non-fatal heart failure and cataract extraction. Risk reduction
      associated with a 10 mm Hg decrease in updated mean systolic blood pressure
      adjusted for specific confounders. RESULTS: The incidence of clinical
      complications was significantly associated with systolic blood pressure, except
      for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood
      pressure was associated with reductions in risk of 12% for any complication
      related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for
      deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction
      (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%,
      P<0.0001). No threshold of risk was observed for any end point. CONCLUSIONS: In
      patients with type 2 diabetes the risk of diabetic complications was strongly
      associated with raised blood pressure. Any reduction in blood pressure is likely
      to reduce the risk of complications, with the lowest risk being in those with
      systolic blood pressure less than 120 mm Hg.

PMID- 10938052
TI  - Prescribing indicators for UK general practice: Delphi consultation study.
AB  - OBJECTIVES: To identify prescribing indicators based on prescribing analysis and
      cost (PACT) data that have face validity for measuring quality or cost
      minimisation. DESIGN: Modified two round Delphi questionnaire requiring
      quantitative and qualitative answers. SETTING: Health authorities in England.
      PARTICIPANTS: All health authority medical and pharmaceutical advisers in the
      first round and lead prescribing advisers for each health authority in the second
      round. MAIN OUTCOME MEASURES: Face validity (median rating of 7-9 on a nine point
      scale without disagreement) and reliability (rating 8 or 9) of indicators for
      assessing quality and cost minimisation. RESULTS: Completed second round
      questionnaires were received from 79 respondents out of 99. The median rating was
      7 for cost minimisation and 6 for quality, and in all except four cases
      individual respondents rated indicators significantly higher for cost than for
      quality. Of the 41 indicators tested, only seven were rated valid and reliable
      for cost minimisation and five for quality. CONCLUSION: The 12 indicators rated
      as valid by leading prescribing advisers had a narrow focus and would allow only
      a limited examination of prescribing at a general practice, primary care group,
      or health authority level.

PMID- 10938053
TI  - Eating a manchineel "beach apple"

PMID- 10938055
TI  - The temperature of underground railway tunnels

PMID- 10938054
TI  - A taxonomy of generic clinical questions: classification study.
AB  - OBJECTIVE: To develop a taxonomy of doctors' questions about patient care that
      could be used to help answer such questions. DESIGN: Use of 295 questions asked
      by Oregon primary care doctors to modify previously developed taxonomy of 1101
      clinical questions asked by Iowa family doctors. SETTING: Primary care practices
      in Iowa and Oregon. PARTICIPANTS: Random samples of 103 Iowa family doctors and
      49 Oregon primary care doctors. MAIN OUTCOME MEASURES: Consensus among seven
      investigators on a meaningful taxonomy of generic questions; interrater
      reliability among 11 individuals who used the taxonomy to classify a random
      sample of 100 questions: 50 from Iowa and 50 from Oregon. RESULTS: The revised
      taxonomy, which comprised 64 generic question types, was used to classify 1396
      clinical questions. The three commonest generic types were "What is the drug of
      choice for condition x?" (150 questions, 11%); "What is the cause of symptom x?"
      (115 questions, 8%); and "What test is indicated in situation x?" (112 questions,
      8%). The mean interrater reliability among 11 coders was moderate (kappa=0.53,
      agreement 55%). CONCLUSIONS: Clinical questions in primary care can be
      categorised into a limited number of generic types. A moderate degree of
      interrater reliability was achieved with the taxonomy developed in this study.
      The taxonomy may enhance our understanding of doctors' information needs and
      improve our ability to meet those needs.

PMID- 10938057
TI  - Treves's young patient

PMID- 10938056
TI  - Stem cell transplantation.

PMID- 10938058
TI  - ABC of oral health. Improving occlusion and orofacial aesthetics: tooth repair
      and replacement.

PMID- 10938059
TI  - Declaration of Helsinki should be strengthened.

PMID- 10938061
TI  - Obituaries

PMID- 10938060
TI  - Dangers of anaesthesia, 1884

PMID- 10938062
TI  - Matrons, medics and maladies: edinburgh royal infirmary in the 1840s

PMID- 10938064
TI  - One flew over the Cuckoo's nest

PMID- 10938063
TI  - Confronting traumatic brain injury

PMID- 10938065
TI  - For most of it I have no words: genocide, landscape and memory

PMID- 10938066
TI  - Hypothetically speaking

PMID- 10938068
TI  - From scalpel to surfboard

PMID- 10938067
TI  - Question capture

PMID- 10938069
TI  - Summer news

PMID- 10938070
TI  - Answers descend, questions ascend

PMID- 10938072
TI  - Risk of childhood diabetes rises with increasing maternal age at delivery

PMID- 10938071
TI  - People with type 2 diabetes should aim at normal blood pressure and HbA(1c)

PMID- 10938074
TI  - Patient management questions asked by primary care doctors fall into 64 generic
      types

PMID- 10938073
TI  - UK prescribing indicators have limited value in assessing practice

PMID- 10938075
TI  - Ethics code should outlaw placebo controlled trials when an accepted treatment
      exists

PMID- 10938076
TI  - Applying for preregistration posts in scotland

PMID- 10938078
TI  - Progressive stabilization of intermediate and transition states in protein
      folding reactions by introducing surface hydrophobic residues.
AB  - It can be argued from the principle of solvent exclusion that the introduction of
      hydrophobic residues onto the surface of a protein will not destabilize the
      folded state because the nonpolar side chain will be at least as exposed in the
      unfolded state as it is when the protein chain is folded. A comparison of the
      folding pathway of wild type and 11 site-directed mutants of CD2.d1 shows this to
      be true. In fact, owing to partial burial of nonpolar groups as folding proceeds,
      we find that the rapidly formed intermediate state and, to a greater extent, the
      transition state are generally stabilized by hydrophobic surface mutations. This
      effect is slightly moderated in the folded state presumably by the perturbation
      of van der Waals' contacts and/or local electrostatic interactions that have a
      greater influence in this fully compact structure. The fact that in all but one
      case we find that stabilization of the rapidly collapsed intermediate is
      accompanied by a faster acquisition of the folded state refutes the argument that
      I states are generally "off pathway" conformations or ensembles that lead to the
      inhibition of otherwise more rapid folding trajectories.

PMID- 10938077
TI  - Tumor necrosis factor alpha-induced phosphorylation of RelA/p65 on Ser529 is
      controlled by casein kinase II.
AB  - Nuclear factor kappaB (NF-kappaB)/Rel transcription factors are key regulators of
      a variety of genes involved in immune and inflammatory responses, growth,
      differentiation, apoptosis, and development. In unstimulated cells, NF-kappaB/Rel
      proteins are sequestered in the cytoplasm by IkappaB inhibitor proteins. Many
      extracellular stimuli, such as tumor necrosis factor alpha (TNFalpha), cause
      rapid phosphorylation of IkappaB at N-terminal serine residues leading to
      ubiquitination and degradation of the inhibitor. Subsequently, NF-kappaB proteins
      translocate to the nucleus and activate gene expression through kappaB response
      elements. TNFalpha, as well as certain other stimuli, also induces the
      phosphorylation of the NF-kappaB proteins. Previously, we have shown that
      TNFalpha induces RelA/p65 phosphorylation at serine 529 and that this inducible
      phosphorylation increases NF-kappaB transcriptional activity on an exogenously
      supplied reporter (). In this report, we demonstrate that casein kinase II (CKII)
      interacts with p65 in vivo and can phosphorylate p65 at serine 529 in vitro. A
      CKII inhibitor (PD144795) inhibited TNFalpha-induced p65 phosphorylation in vivo.
      Furthermore, our results indicate that the association between IkappaBalpha and
      p65 inhibits p65 phosphorylation by CKII and that degradation of IkappaBalpha
      allows CKII to phosphorylate p65 to increase NF-kappaB transactivation potential.
      These data may explain the ability of CKII to modulate cell growth and
      demonstrate a mechanism whereby CKII can function in an inducible manner.

PMID- 10938080
TI  - Requirement of Cyclin/Cdk2 and protein phosphatase 1 activity for chromatin
      assembly factor 1-dependent chromatin assembly during DNA synthesis.
AB  - The influence of reversible protein phosphorylation on nucleosome assembly during
      DNA replication was analyzed in extracts from human cells. Inhibitor studies and
      add-back experiments indicated requirements of cyclin A/Cdk2, cyclin E/Cdk2, and
      protein phosphatase type 1 (PP1) activities for nucleosome assembly during DNA
      synthesis by chromatin assembly factor 1 (CAF-1). The p60 subunit of CAF-1 is a
      molecular target for reversible phosphorylation by cyclin/Cdk complexes and PP1
      during nucleosome assembly and DNA synthesis in vitro. Purified p60 can be
      directly phosphorylated by purified cyclin A/Cdk2, cyclin E/Cdk2, and cyclin
      B1/Cdk1, but not by cyclin D/Cdk4 complexes in vitro. Cyclin B1/Cdk1 triggers
      hyperphosphorylation of p60 in the presence of additional cytosolic factors. CAF
      1 containing hyperphosphorylated p60 prepared from mitotic cells is inactive in
      nucleosome assembly and becomes activated by dephosphorylation in vitro. These
      data provide functional evidence for a requirement of the cell cycle machinery
      for nucleosome assembly by CAF-1 during DNA replication.

PMID- 10938079
TI  - Characterization of a (2R,3R)-2,3-butanediol dehydrogenase as the Saccharomyces
      cerevisiae YAL060W gene product. Disruption and induction of the gene.
AB  - The completion of the Saccharomyces cerevisiae genome project in 1996 showed that
      almost 60% of the potential open reading frames of the genome had no
      experimentally determined function. Using a conserved sequence motif present in
      the zinc-containing medium-chain alcohol dehydrogenases, we found several
      potential alcohol dehydrogenase genes with no defined function. One of these,
      YAL060W, was overexpressed using a multicopy inducible vector, and its protein
      product was purified to homogeneity. The enzyme was found to be a homodimer that,
      in the presence of NAD(+), but not of NADP, could catalyze the stereospecific
      oxidation of (2R,3R)-2, 3-butanediol (K(m) = 14 mm, k(cat) = 78,000 min(-)(1))
      and meso-butanediol (K(m) = 65 mm, k(cat) = 46,000 min(-)(1)) to (3R)-acetoin and
      (3S)-acetoin, respectively. It was unable, however, to further oxidize these
      acetoins to diacetyl. In the presence of NADH, it could catalyze the
      stereospecific reduction of racemic acetoin ((3R/3S)- acetoin; K(m) = 4.5 mm,
      k(cat) = 98,000 min(-)(1)) to (2R,3R)-2,3-butanediol and meso-butanediol,
      respectively. The substrate stereospecificity was determined by analysis of
      products by gas-liquid chromatography. The YAL060W gene product can therefore be
      classified as an NAD-dependent (2R,3R)-2,3-butanediol dehydrogenase (BDH). S.
      cerevisiae could grow on 2,3-butanediol as the sole carbon and energy source.
      Under these conditions, a 3. 5-fold increase in (2R,3R)-2,3-butanediol
      dehydrogenase activity was observed in the total cell extracts. The isoelectric
      focusing pattern of the induced enzyme coincided with that of the pure BDH (pI
      6.9). The disruption of the YAL060W gene was not lethal for the yeast under
      laboratory conditions. The disrupted strain could also grow on 2,3-butanediol,
      although attaining a lesser cell density than the wild-type strain. Taking into
      consideration the substrate specificity of the YAL060W gene product, we propose
      the name of BDH for this gene. The corresponding enzyme is the first eukaryotic
      (2R, 3R)-2,3-butanediol dehydrogenase characterized of the medium-chain
      dehydrogenase/reductase family.

PMID- 10938081
TI  - A proteomics approach to the identification of mammalian mitochondrial small
      subunit ribosomal proteins.
AB  - Mammalian mitochondrial small subunit ribosomal proteins were separated by two
      dimensional polyacrylamide gel electrophoresis. The proteins in six individual
      spots were subjected to in-gel tryptic digestion. Peptides were separated by
      capillary liquid chromatography, and the sequences of selected peptides were
      obtained by electrospray tandem mass spectrometry. The peptide sequences obtained
      were used to screen human expressed sequence tag data bases, and complete
      consensus cDNAs were assembled. Mammalian mitochondrial small subunit ribosomal
      proteins from six different classes of ribosomal proteins were identified. Only
      two of these proteins have significant sequence similarities to ribosomal
      proteins from prokaryotes. These proteins correspond to Escherichia coli S10 and
      S14. Homologs of two human mitochondrial proteins not found in prokaryotes were
      observed in the genomes of Drosophila melanogaster and Caenorhabditis elegans. A
      homolog of one of these proteins was observed in D. melanogaster but not in C.
      elegans, while a homolog of the other was present in C. elegans but not in D.
      melanogaster. A homolog of one of the ribosomal proteins not found in prokaryotes
      was tentatively identified in the yeast genome. This latter protein is the first
      reported example of a ribosomal protein that is shared by mitochondrial ribosomes
      from lower and higher eukaryotes that does not have a homolog in prokaryotes.

PMID- 10938082
TI  - Scavenger receptor BI transfers major lipoprotein-associated phospholipids into
      the cells.
AB  - The phospholipids of lipoproteins can be transferred to cells by an endocytosis
      independent uptake pathway. We analyzed the role of scavenger receptor BI (SR-BI)
      for the selective cellular phospholipid import. Human monocytes rapidly acquired
      the pyrene (py)-labeled phospholipids sphingomyelin (SM), phosphatidylcholine,
      and phosphatidylethanolamine from different donors (low and high density
      lipoproteins (LDL, HDL), lipid vesicles). The anti-SR-BI antibody directed
      against the extracellular loop of the membrane protein lowered the cellular
      import of the phospholipids by 40-80%. The phospholipid transfer from the lipid
      vesicles into the monocytes was suppressed by LDL, HDL, and apoprotein AI.
      Transfection of BHK cells with the cDNA for human SR-BI enhanced the cellular
      import of the vesicle-derived py-phospholipids by 5-6-fold. In the case of the
      LDL donors, transfer of py-SM to the transfected cells was stimulated to a
      greater extent than the uptake of the other py-phospholipids. Similar differences
      were not observed when the vesicles and HDL were used as phospholipid donors. The
      concentration of LDL required for the half-maximal phospholipid import was close
      to the previously reported apparent dissociation constant for LDL binding to SR
      BI. The low activation energy of the SR-BI-mediated py-phospholipid import
      indicated that the transfer occurs entirely in a hydrophobic environment.
      Disruption of cell membrane caveolae by cyclodextrin treatment reduced the SR-BI
      catalyzed incorporation of py-SM, suggesting that intact caveolae are necessary
      for the phospholipid uptake. In conclusion, SR-BI mediates the selective import
      of the major lipoprotein-associated phospholipids into the cells, the transfer
      efficiency being dependent on the structure of the donor lipoprotein.

PMID- 10938083
TI  - Synaptotagmin III/VII isoforms mediate Ca2+-induced insulin secretion in
      pancreatic islet beta -cells.
AB  - Synaptotagmins (Syt) play important roles in Ca(2+)-induced neuroexocytosis.
      Insulin secretion of the pancreatic beta-cell is dependent on an increase in
      intracellular Ca(2+); however, Syt involvement in insulin exocytosis is poorly
      understood. Reverse transcriptase-polymerase chain reaction studies showed the
      presence of Syt isoforms III, IV, V, and VII in rat pancreatic islets, whereas
      Syt isoforms I, II, III, IV, V, VII, and VIII were present in insulin-secreting
      betaTC3 cell. Syt III and VII proteins were identified in rat islets and betaTC3
      and RINm5F beta-cells by immunoblotting. Confocal microscopy showed that Syt III
      and VII co-localized with insulin-containing secretory granules. Two-fold
      overexpression of Syt III in RINm5F beta-cell (Syt III cell) was achieved by
      stable transfection, which conferred greater Ca(2+) sensitivity for exocytosis,
      and resulted in increased insulin secretion. Glyceraldehyde + carbachol-induced
      insulin secretion in Syt III cells was 2.5-fold higher than control empty vector
      cells, whereas potassium-induced secretion was 6-fold higher. In permeabilized
      Syt III cells, Ca(2+)-induced and mastoparan-induced insulin secretion was also
      increased. In Syt VII-overexpressing RINm5F beta-cells, there was amplification
      of carbachol-induced insulin secretion in intact cells and of Ca(2+)-induced and
      mastoparan-induced insulin secretion in permeabilized cells. In conclusion, Syt
      III/VII are located in insulin-containing secretory granules, and we suggest that
      Syt III/VII may be the Ca(2+) sensor or one of the Ca(2+) sensors for insulin
      exocytosis of the beta-cell.

PMID- 10938084
TI  - RNA polymerase II subunit Rpb9 regulates transcription elongation in vivo.
AB  - RNA polymerase II lacking the Rpb9 subunit uses alternate transcription
      initiation sites in vitro and in vivo and is unable to respond to the
      transcription elongation factor TFIIS in vitro. Here, we show that RPB9 has a
      synthetic phenotype with the TFIIS gene. Disruption of RPB9 in yeast also
      resulted in sensitivity to 6-azauracil, which is a phenotype linked to defects in
      transcription elongation. Expression of the TFIIS gene on a high-copy plasmid
      partially suppressed the 6-azauracil sensitivity of Deltarpb9 cells. We set out
      to determine the relevant cellular role of yeast Rpb9 by assessing the ability of
      20 different site-directed and deletion mutants of RPB9 to complement the
      initiation and elongation defects of Deltarpb9 cells in vivo. Rpb9 is composed of
      two zinc ribbons. The N-terminal zinc ribbon restored the wild-type pattern of
      initiation start sites, but was unable to complement the growth defects
      associated with defects in elongation. Most of the site-directed mutants
      complemented the elongation-specific growth phenotypes and reconstituted the
      normal pattern of transcription initiation sites. The anti-correlation between
      the growth defects of cells disrupted for RPB9 and the selection of transcription
      start sites suggests that this is not the primary cellular role for Rpb9. Genome
      wide transcription profiling of Deltarpb9 cells revealed only a few changes,
      predominantly in genes related to metabolism.

PMID- 10938085
TI  - Transcriptional and translational regulation of beta-cell differentiation factor
      Nkx6.1.
AB  - In the mature pancreas, the homeodomain transcription factor Nkx6.1 is uniquely
      restricted to beta-cells. Nkx6.1 also is expressed in developing beta-cells and
      plays an essential role in their differentiation. Among cell lines, both beta-
      and alpha-cell lines express nkx6.1 mRNA; but no protein can be detected in the
      alpha-cell lines, suggesting that post-transcriptional regulation contributes to
      the restriction of Nkx6.1 to beta-cells. To investigate the regulator of Nkx6.1
      expression, we outlined the structure of the mouse nkx6.1 gene, and we identified
      regions that direct cell type-specific expression. The nkx6.1 gene has a long 5'
      untranslated region (5'-UTR) downstream of a cluster of transcription start
      sites. nkx6.1 gene sequences from -5.6 to +1.0 kilobase pairs have specific
      promoter activity in beta-cell lines but not in NIH3T3 cells. This activity is
      dependent on sequences located at about -800 base pairs and on the 5'-UTR.
      Electrophoretic mobility shift assays demonstrate that homeodomain transcription
      factors PDX1 and Nkx2.2 can bind to the sequence element located at -800 base
      pairs. In addition, dicistronic assays establish that the 5'-UTR region functions
      as a potent internal ribosomal entry site, providing cell type-specific
      regulation of translation. These data demonstrate that complex regulation of both
      Nkx6.1 transcription and translation provides the specificity of expression
      required during pancreas development.

PMID- 10938087
TI  - Identification of binding sites on protein targeting to glycogen for enzymes of
      glycogen metabolism.
AB  - The activation of protein phosphastase-1 (PP1) by insulin plays a critical role
      in the regulation of glycogen metabolism. PTG is a PP1 glycogen-targeting
      protein, which also binds the PP1 substrates glycogen synthase, glycogen
      phosphorylase, and phosphorylase kinase (Printen, J. A., Brady, M. J., and
      Saltiel, A. R. (1997) Science 275, 1475-1478). Through a combination of deletion
      analysis and site-directed mutagenesis, the regions on PTG responsible for
      binding PP1 and its substrates have been delineated. Mutagenesis of Val-62 and
      Phe-64 in the highly conserved (K/R)VXF PP1-binding motif to alanine was
      sufficient to ablate PP1 binding to PTG. Phosphorylase kinase, glycogen synthase,
      and phosphorylase binding all mapped to the same C-terminal region of PTG.
      Mutagenesis of Asp-225 and Glu-228 to alanine completely blocked the interaction
      between PTG and these three enzymes, without affecting PP1 binding. Disruption of
      either PP1 or substrate binding to PTG blocked the stimulation of PP1 activity in
      vitro against phosphorylase, indicating that both binding sites may be important
      in PTG action. Transient overexpression of wild-type PTG in Chinese hamster ovary
      cells overexpressing the insulin receptor caused a 50-fold increase in glycogen
      levels. Expression of PTG mutants that do not bind PP1 had no effect on glycogen
      accumulation, indicating that PP1 targeting is essential for PTG function.
      Likewise, expression of the PTG mutants that do not bind PP1 substrates did not
      increase glycogen levels, indicating that PP1 targeting glycogen is not
      sufficient for the metabolic effects of PTG. These results cumulatively
      demonstrate that PTG serves as a molecular scaffold, allowing PP1 to recognize
      its substrates at the glycogen particle.

PMID- 10938088
TI  - Selective degradation of annexins by chaperone-mediated autophagy.
AB  - Annexins are a family of proteins that bind phospholipids in a calcium-dependent
      manner. Analysis of the sequences of the different members of the annexin family
      revealed the presence of a pentapeptide biochemically related to KFERQ in some
      annexins but not in others. Such sequences have been proposed to be a targeting
      sequence for chaperone-mediated autophagy, a lysosomal pathway of protein
      degradation that is activated in confluent cells in response to removal of serum
      growth factors. We demonstrate that annexins II and VI, which contain KFERQ-like
      sequences, are degraded more rapidly in response to serum withdrawal, while
      annexins V and XI, without such sequences, are degraded at the same rate in the
      presence and absence of serum. Using isolated lysosomes, only the annexins
      containing KFERQ-like sequences are degraded by chaperone mediated-autophagy.
      Annexins V and XI could associate with lysosomes but did not enter the lysosomes
      and were not proteolytic substrates. Furthermore, four annexins containing KFERQ
      like sequences, annexins I, II, IV, and VI, are enriched in lysosomes with high
      chaperone-mediated autophagy activity as expected for substrate proteins. These
      results provide striking evidence for the importance of KFERQ motifs in
      substrates of chaperone-mediated autophagy.

PMID- 10938086
TI  - Acetylation increases the alpha-helical content of the histone tails of the
      nucleosome.
AB  - The nature of the structural changes induced by histone acetylation at the
      different levels of chromatin organization has been very elusive. At the histone
      level, it has been proposed on several occasions that acetylation may induce an
      alpha-helical conformation of their acetylated N-terminal domains (tails). In an
      attempt to provide experimental support for this hypothesis, we have purified and
      characterized the tail of histone H4 in its native and mono-, di-, tri-, and
      tetra- acetylated form. The circular dichroism analysis of these peptides shows
      conclusively that acetylation does increase their alpha-helical content.
      Furthermore, the same spectroscopic analysis shows that this is also true for
      both the acetylated nucleosome core particle and the whole histone octamer in
      solution. In contrast to the native tails in which the alpha-helical organization
      appears to be dependent upon interaction of these histone regions with DNA, the
      acetylated tails show an increase in alpha-helical content that does not depend
      on such an interaction.

PMID- 10938089
TI  - The paired homeodomain transcription factor Pax-2 is expressed in the endocrine
      pancreas and transactivates the glucagon gene promoter.
AB  - Glucagon gene expression is controlled by at least four DNA elements within the
      promoter; G2, G3, and G4 confer islet-specific expression, while G1 restricts
      glucagon transcription to alpha cells. Two islet-specific complexes are formed on
      G3, the insulin-responsive element of the glucagon gene; one of these corresponds
      to the paired homeodomain protein Pax-6, a major glucagon gene transactivator
      that plays a crucial role in alpha cell development. We describe here the
      identification of the second complex as Pax-2, another member of the paired box
      family. Pax-2 is known to be crucial for the development of the urogenital tract
      and of the central nervous system, but its presence in the endocrine pancreas has
      not been reported. We detected Pax-2 gene expression by RT-PCR; in islets, Pax-2
      is present as two alternative splicing isoforms, Pax-2A and Pax-2B, whereas in
      the glucagon- and insulin-producing cell lines alphaTC1 and Min6, a distinct
      isoform, Pax-2D2, is found in addition to Pax-2B. Both islet-specific isoforms
      bind to the enhancer element G3 and to the alpha-specific promoter element G1
      that also interacts with Pax-6. Pax-2A and Pax-2B dose-dependently activate
      transcription from the G3 and the G1 elements both in heterologous and in
      glucagon-producing cells. Our data indicate that Pax-2 is the third paired domain
      protein present in the endocrine pancreas and that one of its roles may be the
      regulation of glucagon gene expression.

PMID- 10938090
TI  - Structural characterization of the catalytic active site in the latent and active
      natural gelatinase B from human neutrophils.
AB  - Matrix metalloproteinases are endopeptidases that have a leading role in the
      catabolism of the macromolecular components of the extracellular matrix in a
      variety of normal and pathological processes. Human gelatinase B is a zinc
      dependent proteinase and a member of the matrix metalloproteinase family that is
      involved in inflammation, tissue remodeling, and cancer. We have conducted x-ray
      absorption spectroscopy, atomic emission, and quantum mechanics studies of
      natural and activated human gelatinase B. Our results show that the natural
      enzyme contains one catalytic zinc ion that is central to catalysis. In addition,
      upon enzyme activation, the catalytic zinc site exhibits a conformation change
      that results in the expansion of the bond distances around the zinc ion and the
      replacement of one sulfur with oxygen. Interestingly, quantum mechanics
      calculations show that oxygen ligation at the catalytic zinc ion exhibits a
      greater affinity to the binding of an oxygen from an amino acid residue rather
      than from an external water molecule. These results suggest that the catalytic
      zinc ion plays a key role in both substrate binding and catalysis.

PMID- 10938092
TI  - The cAMP-specific phosphodiesterase PDE4D3 is regulated by phosphatidic acid
      binding. Consequences for cAMP signaling pathway and characterization of a
      phosphatidic acid binding site.
AB  - Hormones and growth factors induce in many cell types the production of
      phosphatidic acid (PA), which has been proposed to play a role as a second
      messenger. We have previously shown in an acellular system that PA selectively
      stimulates certain isoforms of type 4 cAMP-phosphodiesterases (PDE4). Here we
      studied the effect of endogenous PA on PDE activity of transiently transfected
      MA10 cells overexpressing the PA-sensitive isoform PDE4D3. Cell treatment with
      inhibitors of PA degradation, including propranolol, induced an accumulation of
      endogenous PA accompanied by a stimulation of PDE activity and a significant
      decrease in both cAMP levels and protein kinase A activity. Furthermore, in FRTL5
      cells, which natively express PDE4D3, pretreatment with compounds inducing PA
      accumulation prevented both cAMP increase and cAMP-responsive element-binding
      protein phosphorylation triggered by thyroid-stimulating hormone. To determine
      the mechanism of PDE stimulation by PA, endogenous phospholipids were labeled by
      preincubating MA10 cells overexpressing PDE4D3 with [(32)P]orthophosphate. Immuno
      precipitation experiments showed that PA was specifically bound to PDE4D3,
      supporting the hypothesis that PDE4D3 activation occurs through direct binding of
      PA to the protein. PA binding site on PDE4D3 was characterized by engineering
      deletions of selected regions in the N-terminal regulatory domain of the enzyme.
      Deletion of amino acid residues 31-59 suppressed both PA-activating effect and PA
      binding, suggesting that this region rich in basic and hydrophobic residues
      contains the PA binding site. These observations strongly suggest that endogenous
      PA can modulate cAMP levels in intact cells, through a direct activation of
      PDE4D3.

PMID- 10938091
TI  - Central leptin regulates the UCP1 and ob genes in brown and white adipose tissue
      via different beta-adrenoceptor subtypes.
AB  - The three known subtypes of beta-adrenoreceptors (beta(1)-AR, beta(2)-AR, and
      beta(3)-AR) are differentially expressed in brown and white adipose tissue and
      mediate peripheral responses to central modulation of sympathetic outflow by
      leptin. To assess the relative roles of the beta-AR subtypes in mediating
      leptin's effects on adipocyte gene expression, mice with a targeted disruption of
      the beta(3)-adrenoreceptor gene (beta(3)-AR KO) were treated with vehicle or the
      beta(1)/beta(2)-AR selective antagonist, propranolol (20 microgram/g body
      weight/day) prior to intracerebroventricular (ICV) injections of leptin (0.1
      microgram/g body weight/day). Leptin produced a 3-fold increase in UCP1 mRNA in
      brown adipose tissue of wild type (FVB/NJ) and beta(3)-AR KO mice. The response
      was unaltered by propranolol in wild type mice, but was completely blocked by
      this antagonist in beta(3)-AR KO mice. In contrast, ICV leptin had no effect on
      leptin mRNA in either epididymal or retroperitoneal white adipose tissue (WAT)
      from beta(3)-AR KOs. Moreover, propranolol did not block the ability of exogenous
      leptin to reduce leptin mRNA in either WAT depot site of wild type mice. These
      results demonstrate that the beta(3)-AR is required for leptin-mediated
      regulation of ob mRNA expression in WAT, but is interchangeable with the
      beta(1)/beta(2)-ARs in mediating leptin's effect on UCP1 mRNA expression in brown
      adipose tissue.

PMID- 10938093
TI  - The MRP2/cMOAT transporter and arsenic-glutathione complex formation are required
      for biliary excretion of arsenic.
AB  - Worldwide, millions of people are exposed to arsenic in drinking water that
      exceeds the World Health Organization standard of 10 microg/liter by as much as
      50-300-fold, yet little is known about the molecular basis for arsenic excretion.
      Here we show that transport of arsenic into bile depends on the MRP2/cMOAT
      transporter and that glutathione is obligatory for such transport. Using reversed
      phase liquid chromatography/mass spectrometry, we demonstrate that two arsenic
      glutathione complexes not previously identified in vivo, arsenic triglutathione
      and methylarsenic diglutathione, account for most of the arsenic in the bile. The
      structure of the compounds was also confirmed by nuclear magnetic resonance
      spectroscopy. Our findings may help explain the increased susceptibility of
      malnourished human populations to arsenic.

PMID- 10938094
TI  - A tyrosine-sulfated peptide based on the N terminus of CCR5 interacts with a CD4
      enhanced epitope of the HIV-1 gp120 envelope glycoprotein and inhibits HIV-1
      entry.
AB  - The sequential association of the human immunodeficiency virus type 1 (HIV-1)
      envelope glycoprotein gp120 with CD4 and a seven-transmembrane segment coreceptor
      such as CCR5 or CXCR4 initiates entry of the virus into its target cell. The N
      terminus of CCR5, which contains several sulfated tyrosines, plays a critical
      role in the CD4-dependent association of gp120 with CCR5 and in viral entry. Here
      we demonstrate that a tyrosine-sulfated peptide based on the N terminus of CCR5,
      but not its unsulfated analogue, inhibits infection of macrophages and peripheral
      blood mononuclear cells by CCR5-dependent, but not CXCR4-dependent, HIV-1
      isolates. The sulfated peptide also inhibited the association of CCR5-expressing
      cells with gp120-soluble CD4 complexes and, less efficiently, with MIP-1alpha.
      Moreover, this peptide inhibited the precipitation of gp120 by 48d and 23e
      antibodies, which recognize CD4-inducible gp120 epitopes, but not by several
      other antibodies that recognize proximal epitopes. The ability of the sulfated
      peptide to block 48d association with gp120 was dependent in part on seven
      tropism-determining residues in the third variable (V3) and fourth conserved (C4)
      domains of gp120. These data underscore the important role of the N-terminal
      sulfate moieties of CCR5 in the entry of R5 HIV-1 isolates and localize a
      critical contact between gp120 and CCR5.

PMID- 10938096
TI  - Immunocytochemical analyses and targeted gene disruption of GTPBP1.
AB  - We previously identified a gene encoding a putative GTPase, GTPBP1, which is
      structurally related to elongation factor 1alpha, a key component of protein
      biosynthesis machinery. The primary structure of GTPBP1 is highly conserved
      between human and mouse (97% identical at the amino acid level). Expression of
      this gene is enhanced by gamma interferon in a monocytic cell line, THP-1.
      Although counterparts of this molecule in Caenorhabditis elegans and Ascaris suum
      have also been identified, the function of this molecule remains to be clarified.
      In the present study, our immunohistochemical analyses on mouse tissues revealed
      that GTPBP1 is expressed in some neurons and smooth muscle cells of various
      organs as well as macrophages. Immunofluorescence analyses revealed that GTPBP1
      is localized exclusively in cytoplasm and shows a diffuse granular network
      forming a gradient from the nucleus to the periphery of the cells in smooth
      muscle cell lines and macrophages. To investigate the physiological role of
      GTPBP1, we used targeted gene disruption in embryonic stem cells to generate
      GTPBP1-deficient mice. The mutant mice were born at the expected Mendelian
      frequency, developed normally, and were fertile. No manifest anatomical or
      behavioral abnormality was observed in the mutant mice. Functions of macrophages,
      including chemotaxis, phagocytosis, and nitric oxide production, in mutant mice
      were equivalent to those seen in wild-type mice. No significant difference was
      observed in the immune response to protein antigen between mutant mice and wild
      type mice, suggesting normal function of antigen-presenting cells of the mutant
      mice. The absence of an eminent phenotype in GTPBP1-deficient mice may be due to
      functional compensation by GTPBP2, a molecule we recently identified which is
      similar to GTPBP1 in structure and tissue distribution.

PMID- 10938095
TI  - Class II transactivator: mastering the art of major histocompatibility complex
      expression.

PMID- 10938097
TI  - BF-1 interferes with transforming growth factor beta signaling by associating
      with Smad partners.
AB  - The winged-helix (WH) BF-1 gene, which encodes brain factor 1 (BF-1) (also known
      as foxg1), is essential for the proliferation of the progenitor cells of the
      cerebral cortex. Here we show that BF-1-deficient telencephalic progenitor cells
      are more apt to leave the cell cycle in response to transforming growth factor
      beta (TGF-beta) and activin. We found that ectopic expression of BF-1 in vitro
      inhibits TGF-beta mediated growth inhibition and transcriptional activation.
      Surprisingly, we found that the ability of BF-1 to function as a TGF-beta
      antagonist does not require its DNA binding activity. Therefore, we investigated
      whether BF-1 can inhibit Smad-dependent transcriptional responses by interacting
      with Smads or Smad binding partners. We found that BF-1 does not interact with
      Smads. Because the identities of the Smad partners mediating growth inhibition by
      TGF-beta are not clearly established, we examined a model reporter system which
      is known to be activated by activin and TGF-beta through Smads and the WH factor
      FAST-2. We demonstrate that BF-1 associates with FAST-2. This interaction is
      dependent on the same region of protein which mediates its ability to interfere
      with the antiproliferative activity of TGF-beta and with TGF-beta-dependent
      transcriptional activation. Furthermore, the interaction of FAST-2 with BF-1 is
      mediated by the same domain which is required for FAST-2 to interact with Smad2.
      We propose a model in which BF-1 interferes with transcriptional responses to TGF
      beta by interacting with FAST-2 or with other DNA binding proteins which function
      as Smad2 partners and which have a common mode of interaction with Smad2.

PMID- 10938098
TI  - Termination and peptide release at the upstream open reading frame are required
      for downstream translation on synthetic shunt-competent mRNA leaders.
AB  - We have shown recently that a stable hairpin preceded by a short upstream open
      reading frame (uORF) promotes nonlinear ribosome migration or ribosome shunt on a
      synthetic mRNA leader (M. Hemmings-Mieszczak and T. Hohn, RNA 5:1149-1157, 1999).
      We have now used the model mRNA leader to study further the mechanism of shunting
      in vivo and in vitro. We show that a full cycle of translation of the uORF,
      including initiation, elongation, and termination, is a precondition for the
      ribosome shunt across the stem structure to initiate translation downstream.
      Specifically, AUG recognition and the proper release of the nascent peptide are
      necessary and sufficient for shunting. Furthermore, the stop codon context must
      not impede downstream reinitiation. Translation of the main ORF was inhibited by
      replacement of the uORF by coding sequences repressing reinitiation but
      stimulated by the presence of the virus-specific translational transactivator of
      reinitiation (cauliflower mosaic virus pVI). Our results indicate reinitiation as
      the mechanism of translation initiation on the synthetic shunt-competent mRNA
      leader and suggest that uORF-dependent shunting is more prevalent than previously
      anticipated. Within the above constraints, uORF-dependent shunting is quite
      tolerant of uORF and stem sequences and operates in systems as diverse as plants
      and fungi.

PMID- 10938099
TI  - Prothymosin alpha selectively enhances estrogen receptor transcriptional activity
      by interacting with a repressor of estrogen receptor activity.
AB  - We find that prothymosin alpha (PTalpha) selectively enhances transcriptional
      activation by the estrogen receptor (ER) but not transcriptional activity of
      other nuclear hormone receptors. This selectivity for ER is explained by PTalpha
      interaction not with ER, but with a 37-kDa protein denoted REA, for repressor of
      estrogen receptor activity, a protein that we have previously shown binds to ER,
      blocking coactivator binding to ER. We isolated PTalpha, known to be a chromatin
      remodeling protein associated with cell proliferation, using REA as bait in a
      yeast two-hybrid screen with a cDNA library from MCF-7 human breast cancer cells.
      PTalpha increases the magnitude of ERalpha transcriptional activity three- to
      fourfold. It shows lesser enhancement of ERbeta transcriptional activity and has
      no influence on the transcriptional activity of other nuclear hormone receptors
      (progesterone receptor, glucocorticoid receptor, thyroid hormone receptor, or
      retinoic acid receptor) or on the basal activity of ERs. In contrast, the steroid
      receptor coactivator SRC-1 increases transcriptional activity of all of these
      receptors. Cotransfection of PTalpha or SRC-1 with increasing amounts of REA, as
      well as competitive glutathione S-transferase pulldown and mammalian two-hybrid
      studies, show that REA competes with PTalpha (or SRC-1) for regulation of ER
      transcriptional activity and suppresses the ER stimulation by PTalpha or SRC-1,
      indicating that REA can function as an anticoactivator in cells. Our data support
      a model in which PTalpha, which does not interact with ER, selectively enhances
      the transcriptional activity of the ER but not that of other nuclear receptors by
      recruiting the repressive REA protein away from ER, thereby allowing effective
      coactivation of ER with SRC-1 or other coregulators. The ability of PTalpha to
      directly interact in vitro and in vivo with REA, a selective coregulator of the
      ER, thereby enabling the interaction of ER with coactivators, appears to explain
      its ability to selectively enhance ER transcriptional activity. These findings
      highlight a new role for PTalpha as a coregulator activity-modulating protein
      that confers receptor specificity. Proteins such as PTalpha represent an
      additional regulatory component that defines a novel paradigm enabling receptor
      selective enhancement of transcriptional activity by coactivators.

PMID- 10938100
TI  - The molecular chaperone activity of simian virus 40 large T antigen is required
      to disrupt Rb-E2F family complexes by an ATP-dependent mechanism.
AB  - The simian virus 40 large T antigen (T antigen) inactivates tumor suppressor
      proteins and therefore has been used in numerous studies to probe the mechanisms
      that control cellular growth and to generate immortalized cell lines. Binding of
      T antigen to the Rb family of growth-regulatory proteins is necessary but not
      sufficient to cause transformation. The molecular mechanism underlying T-antigen
      inactivation of Rb function is poorly understood. In this study we show that T
      antigen associates with pRb and p130-E2F complexes in a stable manner. T antigen
      dissociates from a p130-E2F-4-DP-1 complex, coincident with the release of p130
      from E2F-4-DP-1. The dissociation of this complex requires Hsc70, ATP, and a
      functional T-antigen J domain. We also report that the "released" E2F-DP-1
      complex is competent to bind DNA containing an E2F consensus binding site. We
      propose that T antigen disrupts Rb-E2F family complexes through the action of its
      J domain and Hsc70. These findings indicate how Hsc70 supports T-antigen action
      and help to explain the cis requirement for a J domain and Rb binding motif in T
      antigen-induced transformation. Furthermore, this is the first demonstration
      linking Hsc70 ATP hydrolysis to the release of E2F bound by Rb family members.

PMID- 10938101
TI  - Gic2p may link activated Cdc42p to components involved in actin polarization,
      including Bni1p and Bud6p (Aip3p).
AB  - Gic2p is a Cdc42p effector which functions during cytoskeletal organization at
      bud emergence and in response to pheromones, but it is not understood how Gic2p
      interacts with the actin cytoskeleton. Here we show that Gic2p displayed multiple
      genetic interactions with Bni1p, Bud6p (Aip3p), and Spa2p, suggesting that Gic2p
      may regulate their function in vivo. In support of this idea, Gic2p
      cofractionated with Bud6p and Spa2p and interacted with Bud6p by
      coimmunoprecipitation and two-hybrid analysis. Importantly, localization of Bni1p
      and Bud6p to the incipient bud site was dependent on active Cdc42p and the Gic
      proteins but did not require an intact actin cytoskeleton. We identified a
      conserved domain in Gic2p which was necessary for its polarization function but
      dispensable for binding to Cdc42p-GTP and its localization to the site of
      polarization. Expression of a mutant Gic2p harboring a single-amino-acid
      substitution in this domain (Gic2p(W23A)) interfered with polarized growth in a
      dominant-negative manner and prevented recruitment of Bni1p and Bud6p to the
      incipient bud site. We propose that at bud emergence, Gic2p functions as an
      adaptor which may link activated Cdc42p to components involved in actin
      organization and polarized growth, including Bni1p, Spa2p, and Bud6p.

PMID- 10938103
TI  - Targeted disruption of the mPer3 gene: subtle effects on circadian clock
      function.
AB  - Neurons in the mammalian suprachiasmatic nucleus (SCN) contain a cell-autonomous
      circadian clock that is based on a transcriptional-translational feedback loop.
      The basic helix-loop-helix-PAS proteins CLOCK and BMAL1 are positive regulators
      and drive the expression of the negative regulators CRY1 and CRY2, as well as
      PER1, PER2, and PER3. To assess the role of mouse PER3 (mPER3) in the circadian
      timing system, we generated mice with a targeted disruption of the mPer3 gene.
      Western blot analysis confirmed the absence of mPER3-immunoreactive proteins in
      mice homozygous for the targeted allele. mPer1, mPer2, mCry1, and Bmal1 RNA
      rhythms in the SCN did not differ between mPER3-deficient and wild-type mice.
      Rhythmic expression of mPer1 and mPer2 RNAs in skeletal muscle also did not
      differ between mPER3-deficient and wild-type mice. mPer3 transcripts were
      rhythmically expressed in the SCN and skeletal muscle of mice homozygous for the
      targeted allele, but the level of expression of the mutant transcript was lower
      than that in wild-type controls. Locomotor activity rhythms in mPER3-deficient
      mice were grossly normal, but the circadian cycle length was significantly (0.5
      h) shorter than that in controls. The results demonstrate that mPer3 is not
      necessary for circadian rhythms in mice.

PMID- 10938102
TI  - Eukaryotic translation initiation factor 4GI is a cellular target for NS1
      protein, a translational activator of influenza virus.
AB  - Influenza virus NS1 protein is an RNA-binding protein whose expression alters
      several posttranscriptional regulatory processes, like polyadenylation, splicing,
      and nucleocytoplasmic transport of cellular mRNAs. In addition, NS1 protein
      enhances the translational rate of viral, but not cellular, mRNAs. To
      characterize this effect, we looked for targets of NS1 influenza virus protein
      among cellular translation factors. We found that NS1 coimmunoprecipitates with
      eukaryotic initiation factor 4GI (eIF4GI), the large subunit of the cap-binding
      complex eIF4F, either in influenza virus-infected cells or in cells transfected
      with NS1 cDNA. Affinity chromatography studies using a purified His-NS1 protein
      containing matrix showed that the fusion protein pulls down endogenous eIF4GI
      from COS-1 cells and labeled eIF4GI translated in vitro, but not the eIF4E
      subunit of the eIF4F factor. Similar in vitro binding experiments with eIF4GI
      deletion mutants indicated that the NS1-binding domain of eIF4GI is located
      between residues 157 and 550, in a region where no other component of the
      translational machinery is known to interact. Moreover, using overlay assays and
      pull-down experiments, we showed that NS1 and eIF4GI proteins interact directly,
      in an RNA-independent manner. Mapping of the eIF4GI-binding domain in the NS1
      protein indicated that the first 113 N-terminal amino acids of the protein, but
      not the first 81, are sufficient to bind eIF4GI. The first of these mutants has
      been previously shown to act as a translational enhancer, while the second is
      defective in this activity. Collectively, these and previously published data
      suggest a model where NS1 recruits eIF4GI specifically to the 5' untranslated
      region (5' UTR) of the viral mRNA, allowing for the preferential translation of
      the influenza virus messengers.

PMID- 10938104
TI  - Potentiation of GATA-2 activity through interactions with the promyelocytic
      leukemia protein (PML) and the t(15;17)-generated PML-retinoic acid receptor
      alpha oncoprotein.
AB  - The hematopoietically expressed GATA family of transcription factors function as
      key regulators of blood cell fate. Among these, GATA-2 is implicated in the
      survival and growth of multipotential progenitors. Here we report that the
      promyelocytic leukemia protein (PML) can complex with GATA-2 and potentiate its
      transactivation capacity. The binding is mediated through interaction of the zinc
      finger region of GATA-2 and the B-box domain of PML. The B-box region of PML is
      retained in the PML-RARalpha (retinoic acid receptor alpha) fusion protein
      generated by the t(15;17) translocation characteristic of acute promyelocytic
      leukemia (APL). Consistent with this, we provide evidence that GATA-2 can
      physically associate with PML-RARalpha. Functional experiments further
      demonstrated that this interaction has the capacity to render GATA-dependent
      transcription inducible by retinoic acid, raising the possibility that GATA
      target genes may be involved in the molecular pathogenesis of APL.

PMID- 10938105
TI  - The RNA-binding protein TIA-1 is a novel mammalian splicing regulator acting
      through intron sequences adjacent to a 5' splice site.
AB  - Splicing of the K-SAM alternative exon of the fibroblast growth factor receptor 2
      gene is heavily dependent on the U-rich sequence IAS1 lying immediately
      downstream from its 5' splice site. We show that IAS1 can activate the use of
      several heterologous 5' splice sites in vitro. Addition of the RNA-binding
      protein TIA-1 to splicing extracts preferentially enhances the use of 5' splice
      sites linked to IAS1. TIA-1 can provoke a switch to use of such sites on pre
      mRNAs with competing 5' splice sites, only one of which is adjacent to IAS1.
      Using a combination of UV cross-linking and specific immunoprecipitation steps,
      we show that TIA-1 binds to IAS1 in cell extracts. This binding is stronger if
      IAS1 is adjacent to a 5' splice site and is U1 snRNP dependent. Overexpression of
      TIA-1 in cultured cells activates K-SAM exon splicing in an IAS1-dependent
      manner. If IAS1 is replaced with a bacteriophage MS2 operator, splicing of the K
      SAM exon can no longer be activated by TIA-1. Splicing can, however, be activated
      by a TIA-1-MS2 coat protein fusion, provided that the operator is close to the 5'
      splice site. Our results identify TIA-1 as a novel splicing regulator, which acts
      by binding to intron sequences immediately downstream from a 5' splice site in a
      U1 snRNP-dependent fashion. TIA-1 is distantly related to the yeast U1 snRNP
      protein Nam8p, and the functional similarities between the two proteins are
      discussed.

PMID- 10938106
TI  - p12(DOC-1) is a novel cyclin-dependent kinase 2-associated protein.
AB  - Regulated cyclin-dependent kinase (CDK) levels and activities are critical for
      the proper progression of the cell division cycle. p12(DOC-1) is a growth
      suppressor isolated from normal keratinocytes. We report that p12(DOC-1)
      associates with CDK2. More specifically, p12(DOC-1) associates with the monomeric
      nonphosphorylated form of CDK2 (p33CDK2). Ectopic expression of p12(DOC-1)
      resulted in decreased cellular CDK2 and reduced CDK2-associated kinase activities
      and was accompanied by a shift in the cell cycle positions of p12(DOC-1)
      transfectants ( upward arrow G(1) and downward arrow S). The p12(DOC-1)-mediated
      decrease of CDK2 was prevented if the p12(DOC-1) transfectants were grown in the
      presence of the proteosome inhibitor clasto-lactacystin beta-lactone, suggesting
      that p12(DOC-1) may target CDK2 for proteolysis. A CDK2 binding mutant was
      created and was found to revert p12(DOC-1)-mediated, CDK2-associated cell cycle
      phenotypes. These data support p12(DOC-1) as a specific CDK2-associated protein
      that negatively regulates CDK2 activities by sequestering the monomeric pool of
      CDK2 and/or targets CDK2 for proteolysis, reducing the active pool of CDK2.

PMID- 10938107
TI  - Replication of heterochromatin and structure of polytene chromosomes.
AB  - Heterochromatin is characteristically the last portion of the genome to be
      replicated. In polytene cells, heterochromatic sequences are underreplicated
      because S phase ends before replication of heterochromatin is completed.
      Truncated heterochromatic DNAs have been identified in polytene cells of
      Drosophila and may be the discontinuous molecules that form between fully
      replicated euchromatic and underreplicated heterochromatic regions of the
      chromosome. In this report, we characterize the temporal pattern of
      heterochromatic DNA truncation during development of polytene cells.
      Underreplication occurred during the first polytene S phase, yet DNA truncation,
      which was found within heterochromatic sequences of all four Drosophila
      chromosomes, did not occur until the second polytene S phase. DNA truncation was
      correlated with underreplication, since increasing the replication of satellite
      sequences with the cycE(1672) mutation caused decreased production of truncated
      DNAs. Finally, truncation of heterochromatic DNAs was neither quantitatively nor
      qualitatively affected by modifiers of position effect variegation including the
      Y chromosome, Su(var)205(2), parental origin, or temperature. We propose that
      heterochromatic satellite sequences present a barrier to DNA replication and that
      replication forks that transiently stall at such barriers in late S phase of
      diploid cells are left unresolved in the shortened S phase of polytene cells. DNA
      truncation then occurs in the second polytene S phase, when new replication forks
      extend to the position of forks left unresolved in the first polytene S phase.

PMID- 10938108
TI  - Plant enzymes but not Agrobacterium VirD2 mediate T-DNA ligation in vitro.
AB  - Agrobacterium tumefaciens, a gram-negative soil bacterium, transfers DNA to many
      plant species. In the plant cell, the transferred DNA (T-DNA) is integrated into
      the genome. An in vitro ligation-integration assay has been designed to
      investigate the mechanism of T-DNA ligation and the factors involved in this
      process. The VirD2 protein, which is produced in Agrobacterium and is covalently
      attached to T-DNA, did not, under our assay conditions, ligate T-DNA to a model
      target sequence in vitro. We tested whether plant extracts could ligate T-DNA to
      target oligonucleotides in our test system. The in vitro ligation-integration
      reaction did indeed take place in the presence of plant extracts. This reaction
      was inhibited by dTTP, indicating involvement of a plant DNA ligase. We found
      that prokaryotic DNA ligases could substitute for plant extracts in this
      reaction. Ligation of the VirD2-bound oligonucleotide to the target sequence
      mediated by T4 DNA ligase was less efficient than ligation of a free
      oligonucleotide to the target. T-DNA ligation mediated by a plant enzyme(s) or T4
      DNA ligase requires ATP.

PMID- 10938110
TI  - The poly(A)-binding protein and an mRNA stability protein jointly regulate an
      endoribonuclease activity.
AB  - We previously identified a sequence-specific erythroid cell-enriched
      endoribonuclease (ErEN) activity involved in the turnover of the stable alpha
      globin mRNA. We now demonstrate that ErEN activity is regulated by the poly(A)
      tail. The unadenylated alpha-globin 3' untranslated region (3'UTR) was an
      efficient substrate for ErEN cleavage, while the polyadenylated 3'UTR was
      inefficiently cleaved in an in vitro decay assay. The influence of the poly(A)
      tail was mediated through the poly(A)-binding protein (PABP) bound to the poly(A)
      tail, which can inhibit ErEN activity. ErEN cleavage of an adenylated alpha
      globin 3'UTR was accentuated upon depletion of PABP from the cytosolic extract,
      while addition of recombinant PABP reestablished the inhibition of
      endoribonuclease cleavage. PABP inhibited ErEN activity indirectly through an
      interaction with the alphaCP mRNA stability protein. Sequestration of alphaCP
      resulted in an increase of ErEN cleavage activity, regardless of the
      polyadenylation state of the RNA. Using electrophoretic mobility shift assays,
      PABP was shown to enhance the binding efficiency of alphaCP to the alpha-globin
      3'UTR, which in turn protected the ErEN target sequence. Conversely, the binding
      of PABP to the poly(A) tail was also augmented by alphaCP, implying that a stable
      higher-order structural network is involved in stabilization of the alpha-globin
      mRNA. Upon deadenylation, the interaction of PABP with alphaCP would be
      disrupted, rendering the alpha-globin 3'UTR more susceptible to endoribonuclease
      cleavage. The data demonstrated a specific role for PABP in protecting the body
      of an mRNA in addition to demonstrating PABP's well-characterized effect of
      stabilizing the poly(A) tail.

PMID- 10938109
TI  - Insulin-activated protein kinase Cbeta bypasses Ras and stimulates mitogen
      activated protein kinase activity and cell proliferation in muscle cells.
AB  - In L6 muscle cells expressing wild-type human insulin receptors (L6hIR), insulin
      induced protein kinase Calpha (PKCalpha) and beta activities. The expression of
      kinase-deficient IR mutants abolished insulin stimulation of these PKC isoforms,
      indicating that receptor kinase is necessary for PKC activation by insulin. In
      L6hIR cells, inhibition of insulin receptor substrate 1 (IRS-1) expression caused
      a 90% decrease in insulin-induced PKCalpha and -beta activation and blocked
      insulin stimulation of mitogen-activated protein kinase (MAPK) and DNA synthesis.
      Blocking PKCbeta with either antisense oligonucleotide or the specific inhibitor
      LY379196 decreased the effects of insulin on MAPK activity and DNA synthesis by
      >80% but did not affect epidermal growth factor (EGF)- and serum-stimulated
      mitogenesis. In contrast, blocking c-Ras with lovastatin or the use of the
      L61,S186 dominant negative Ras mutant inhibited insulin-stimulated MAPK activity
      and DNA synthesis by only about 30% but completely blocked the effect of EGF.
      PKCbeta block did not affect Ras activity but almost completely inhibited insulin
      induced Raf kinase activation and coprecipitation with PKCbeta. Finally, blocking
      PKCalpha expression by antisense oligonucleotide constitutively increased MAPK
      activity and DNA synthesis, with little effect on their insulin sensitivity. We
      make the following conclusions. (i) The tyrosine kinase activity of the IR is
      necessary for insulin activation of PKCalpha and -beta. (ii) IRS-1
      phosphorylation is necessary for insulin activation of these PKCs in the L6
      cells. (iii) In these cells, PKCbeta plays a unique Ras-independent role in
      mediating insulin but not EGF or other growth factor mitogenic signals.

PMID- 10938111
TI  - Selective DNA binding and association with the CREB binding protein coactivator
      contribute to differential activation of alpha/beta interferon genes by
      interferon regulatory factors 3 and 7.
AB  - Recent studies implicate the interferon (IFN) regulatory factors (IRF) IRF-3 and
      IRF-7 as key activators of the alpha/beta IFN (IFN-alpha/beta) genes as well as
      the RANTES chemokine gene. Using coexpression analysis, the human IFNB, IFNA1,
      and RANTES promoters were stimulated by IRF-3 coexpression, whereas the IFNA4,
      IFNA7, and IFNA14 promoters were preferentially induced by IRF-7 only. Chimeric
      proteins containing combinations of different IRF-7 and IRF-3 domains were also
      tested, and the results provided evidence of distinct DNA binding properties of
      IRF-3 and IRF-7, as well as a preferential association of IRF-3 with the CREB
      binding protein (CBP) coactivator. Interestingly, some of these fusion proteins
      led to supraphysiological levels of IFN promoter activation. DNA binding site
      selection studies demonstrated that IRF-3 and IRF-7 bound to the 5'-GAAANNGAAANN
      3' consensus motif found in many virus-inducible genes; however, a single
      nucleotide substitution in either of the GAAA half-site motifs eliminated IRF-3
      binding and transactivation activity but did not affect IRF-7 interaction or
      transactivation activity. These studies demonstrate that IRF-3 possesses a
      restricted DNA binding site specificity and interacts with CBP, whereas IRF-7 has
      a broader DNA binding specificity that contributes to its capacity to stimulate
      delayed-type IFN gene expression. These results provide an explanation for the
      differential regulation of IFN-alpha/beta gene expression by IRF-3 and IRF-7 and
      suggest that these factors have complementary rather than redundant roles in the
      activation of the IFN-alpha/beta genes.

PMID- 10938112
TI  - Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex
      disassembly.
AB  - The p21-activated kinase PAK is targeted to focal complexes (FCs) through
      interactions with the SH3 domains of the PAK-interacting exchange factor PIX and
      Nck. PIX is a Rac GTP exchange factor that also binds the G-protein-coupled
      receptor kinase-interacting protein known as GIT1. Overexpression of GIT1 in
      fibroblasts or epithelial cells causes a loss of paxillin from FCs and stimulates
      cell motility. This is due to the direct interaction of a C-terminal 125-residue
      domain of GIT1 with paxillin, under the regulation of PIX. In its activated
      state, GIT1 can promote FC disassembly independent of actin-myosin contractile
      events. Additionally, GIT directly couples to a key component of FCs, focal
      adhesion kinase (FAK), via a conserved Spa2 homology domain. We propose that GIT1
      and FAK cooperate to promote motility both by directly regulating focal complex
      dynamics and by the activation of Rac.

PMID- 10938113
TI  - Vav family proteins couple to diverse cell surface receptors.
AB  - Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which
      activate pathways leading to actin cytoskeletal rearrangements and
      transcriptional alterations. Vav proteins contain several protein binding domains
      which can link cell surface receptors to downstream signaling proteins. Vav1 is
      expressed exclusively in hematopoietic cells and tyrosine phosphorylated in
      response to activation of multiple cell surface receptors. However, it is not
      known whether the recently identified isoforms Vav2 and Vav3, which are broadly
      expressed, can couple with similar classes of receptors, nor is it known whether
      all Vav isoforms possess identical functional activities. We expressed Vav1,
      Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav
      proteins to receptor activation. Although each Vav isoform was tyrosine
      phosphorylated upon activation of representative receptor tyrosine kinases,
      integrin, and lymphocyte antigen receptors, we found unique aspects of Vav
      protein coupling in each receptor pathway. Each Vav protein coprecipitated with
      activated epidermal growth factor and platelet-derived growth factor (PDGF)
      receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor
      were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine
      phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless
      the protein tyrosine kinase Syk was also expressed, suggesting that integrin
      activation of Vav proteins may be restricted to cell types that express
      particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or
      Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT
      dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFkappaB
      dependent transcription. Thus, although each Vav isoform can respond to similar
      cell surface receptors, there are isoform-specific differences in their
      activation of downstream signaling pathways.

PMID- 10938114
TI  - mRNA stability and polysome loss in hibernating Arctic ground squirrels
      (Spermophilus parryii).
AB  - All small mammalian hibernators periodically rewarm from torpor to high,
      euthermic body temperatures for brief intervals throughout the hibernating
      season. The functional significance of these arousal episodes is unknown, but one
      suggestion is that rewarming may be related to replacement of gene products lost
      during torpor due to degradation of mRNA. To assess the stability of mRNA as a
      function of the hibernation state, we examined the poly(A) tail lengths of liver
      mRNA from arctic ground squirrels sacrificed during four hibernation states
      (early and late during a torpor bout and early and late following arousal from
      torpor) and from active ground squirrels sacrificed in the summer. Poly(A) tail
      lengths were not altered during torpor, suggesting either that mRNA is stabilized
      or that transcription continues during torpor. In mRNA isolated from torpid
      ground squirrels, we observed a pattern of 12 poly(A) residues at greater
      densities approximately every 27 nucleotides along the poly(A) tail, which is a
      pattern consistent with binding of poly(A)-binding protein. The intensity of this
      pattern was significantly reduced following arousal from torpor and undetectable
      in mRNA obtained from summer ground squirrels. Analyses of polysome profiles
      revealed a significant reduction in polyribosomes in torpid animals, indicating
      that translation is depressed during torpor.

PMID- 10938115
TI  - Octamer transfer and creation of stably remodeled nucleosomes by human SWI-SNF
      and its isolated ATPases.
AB  - Chromatin remodeling complexes help regulate the structure of chromatin to
      facilitate transcription. The multisubunit human (h) SWI-SNF complex has been
      shown to remodel mono- and polynucleosome templates in an ATP-dependent manner.
      The isolated hSWI-SNF ATPase subunits BRG1 and hBRM also have these activities.
      The intact complex has been shown to produce a stable remodeled dimer of
      mononucleosomes as a product. Here we show that the hSWI-SNF ATPases alone can
      also produce this product. In addition, we show that hSWI-SNF and its ATPases
      have the ability to transfer histone octamers from donor nucleosomes to acceptor
      DNA. These two reactions are characterized and compared. Our results are
      consistent with both products of SWI-SNF action being formed as alternative
      outcomes of a single remodeling mechanism. The ability of the isolated ATPase
      subunits to catalyze these reactions suggests that these subunits play a key role
      in determining the mechanistic capabilities of the SWI-SNF family of remodeling
      complexes.

PMID- 10938117
TI  - Sgs1 helicase activity is required for mitotic but apparently not for meiotic
      functions.
AB  - The SGS1 gene of Saccharomyces cerevisiae is a homologue for the Bloom's syndrome
      and Werner's syndrome genes. The disruption of the SGS1 gene resulted in very
      poor sporulation, and the majority of the cells were arrested at the
      mononucleated stage. The recombination frequency measured by a return-to-growth
      assay was reduced considerably in sgs1 disruptants. However, double-strand break
      formation, which is a key event in the initiation of meiotic DNA recombination,
      occurred; crossover and noncrossover products were observed in the disruptants,
      although the amounts of these products were slightly decreased compared with
      those in wild-type cells. The spores produced by sgs1 disruptants showed
      relatively high viability. The sgs1 spo13 double disruptants sporulated poorly,
      like the sgs1 disruptants, but spore viability was reduced much more than with
      either sgs1 or spo13 single disruptants. Disruption of the RED1 or RAD17 gene
      partially alleviated the poor-sporulation phenotype of sgs1 disruptants,
      indicating that portions of the population of sgs1 disruptants are blocked by the
      meiotic checkpoint. The poor sporulation of sgs1 disruptants was complemented
      with a mutated SGS1 gene encoding a protein lacking DNA helicase activity;
      however, the mutated gene could suppress neither the sensitivity of sgs1
      disruptants to methyl methanesulfonate and hydroxyurea nor the mitotic
      hyperrecombination phenotype of sgs1 disruptants.

PMID- 10938118
TI  - Ras-guanine nucleotide exchange factor sos2 is dispensable for mouse growth and
      development.
AB  - The mammalian sos1 and sos2 genes encode highly homologous members of the Son-of
      sevenless family of guanine nucleotide exchange factors. They are ubiquitously
      expressed and play key roles in transmission of signals initiated by surface
      protein tyrosine kinases that are transduced into the cell through the action of
      membrane-associated Ras proteins. Recent reports showed that targeted disruption
      of the sos1 locus results in embryonic lethality. To gain insight into the in
      vivo function of sos2, we disrupted its catalytic CDC25-H domain by means of gene
      targeting techniques. Mating among heterozygous sos2(+/-) mice produced viable
      sos2(-/-) offspring with a normal Mendelian pattern of inheritance, indicating
      that the loss of sos2 does not interfere with embryo viability in the uterus.
      Adult homozygous mutant sos2(-/-) mice reached sexual maturity at the same age as
      their wild-type littermates, and both male and female null mutants were fertile.
      Histopathological analysis showed no observable differences between mutant and
      wild-type mice. Our results show that unlike the case for sos1, sos2 gene
      function is dispensable for normal mouse development, growth, and fertility.

PMID- 10938116
TI  - Functional studies on the candidate ATPase domains of Saccharomyces cerevisiae
      MutLalpha.
AB  - Saccharomyces cerevisiae MutL homologues Mlh1p and Pms1p form a heterodimer,
      termed MutLalpha, that is required for DNA mismatch repair after mismatch binding
      by MutS homologues. Recent sequence and structural studies have placed the NH(2)
      termini of MutL homologues in a new family of ATPases. To address the functional
      significance of this putative ATPase activity in MutLalpha, we mutated conserved
      motifs for ATP hydrolysis and ATP binding in both Mlh1p and Pms1p and found that
      these changes disrupted DNA mismatch repair in vivo. Limited proteolysis with
      purified recombinant MutLalpha demonstrated that the NH(2) terminus of MutLalpha
      undergoes conformational changes in the presence of ATP and nonhydrolyzable ATP
      analogs. Furthermore, two-hybrid analysis suggested that these ATP-binding
      induced conformational changes promote an interaction between the NH(2) termini
      of Mlh1p and Pms1p. Surprisingly, analysis of specific mutants suggested
      differential requirements for the ATPase motifs of Mlh1p and Pms1p during DNA
      mismatch repair. Taken together, these results suggest that MutLalpha undergoes
      ATP-dependent conformational changes that may serve to coordinate downstream
      events during yeast DNA mismatch repair.

PMID- 10938119
TI  - Multiple splicing defects in an intronic false exon.
AB  - Splice site consensus sequences alone are insufficient to dictate the recognition
      of real constitutive splice sites within the typically large transcripts of
      higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites
      with good matches to the consensus sequences can be easily designated. In an
      attempt to identify elements that prevent pseudoexon splicing, we have
      systematically altered known splicing signals, as well as immediately adjacent
      flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the
      human hprt gene. The substitution of a 5' splice site that perfectly matches the
      5' consensus combined with mutation to match the CAG/G sequence of the 3'
      consensus failed to get this model pseudoexon included as the central exon in a
      dhfr minigene context. Provision of a real 3' splice site and a consensus 5'
      splice site and removal of an upstream inhibitory sequence were necessary and
      sufficient to confer splicing on the pseudoexon. This activated context also
      supported the splicing of a second pseudoexon sequence containing no apparent
      enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of
      the pseudoexon are defective despite their good agreement with the consensus. On
      the other hand, the pseudoexon body did not exert a negative influence on
      splicing. The introduction into the pseudoexon of a sequence selected for binding
      to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the
      effect of the upstream negative element and the defective polypyrimidine tract.
      These results support the idea that exon-bridging enhancers are not a
      prerequisite for constitutive exon definition and suggest that intrinsically
      defective splice sites and negative elements play important roles in
      distinguishing the real splicing signal from the vast number of false splicing
      signals.

PMID- 10938120
TI  - Protein kinase A and mitogen-activated protein kinase pathways antagonistically
      regulate fission yeast fbp1 transcription by employing different modes of action
      at two upstream activation sites.
AB  - A significant challenge to our understanding of eukaryotic transcriptional
      regulation is to determine how multiple signal transduction pathways converge on
      a single promoter to regulate transcription in divergent fashions. To study this,
      we have investigated the transcriptional regulation of the Schizosaccharomyces
      pombe fbp1 gene that is repressed by a cyclic AMP (cAMP)-dependent protein kinase
      A (PKA) pathway and is activated by a stress-activated mitogen-activated protein
      kinase (MAPK) pathway. In this study, we identified and characterized two cis
      acting elements in the fbp1 promoter required for activation of fbp1
      transcription. Upstream activation site 1 (UAS1), located approximately 900 bp
      from the transcriptional start site, resembles a cAMP response element (CRE) that
      is the binding site for the atf1-pcr1 heterodimeric transcriptional activator.
      Binding of this activator to UAS1 is positively regulated by the MAPK pathway and
      negatively regulated by PKA. UAS2, located approximately 250 bp from the
      transcriptional start site, resembles a Saccharomyces cerevisiae stress response
      element. UAS2 is bound by transcriptional activators and repressors regulated by
      both the PKA and MAPK pathways, although atf1 itself is not present in these
      complexes. Transcriptional regulation of fbp1 promoter constructs containing only
      UAS1 or UAS2 confirms that the PKA and MAPK regulation is targeted to both sites.
      We conclude that the PKA and MAPK signal transduction pathways regulate fbp1
      transcription at UAS1 and UAS2, but that the antagonistic interactions between
      these pathways involve different mechanisms at each site.

PMID- 10938121
TI  - Cell cycle-dependent binding of yeast heat shock factor to nucleosomes.
AB  - In the nucleus, transcription factors must contend with the presence of chromatin
      in order to gain access to their cognate regulatory sequences. As most nuclear
      DNA is assembled into nucleosomes, activators must either invade a stable,
      preassembled nucleosome or preempt the formation of nucleosomes on newly
      replicated DNA, which is transiently free of histones. We have investigated the
      mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock
      elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82
      DeltaHSE1). We find that activated HSF cannot bind a stable, sequence-positioned
      nucleosome in G(1)-arrested cells. It can do so readily, however, following
      release from G(1) arrest or after the imposition of either an early S- or late
      G(2)-phase arrest. Surprisingly, despite the S-phase requirement, HSF nucleosomal
      binding activity is restored in the absence of hsp82 replication. These results
      contrast with the prevailing paradigm for activator-nucleosome interactions and
      implicate a nonreplicative, S-phase-specific event as a prerequisite for HSF
      binding to nucleosomal sites in vivo.

PMID- 10938122
TI  - Molecular determinants for targeting heterochromatin protein 1-mediated gene
      silencing: direct chromoshadow domain-KAP-1 corepressor interaction is essential.
AB  - The KRAB domain is a highly conserved transcription repression module commonly
      found in eukaryotic zinc finger proteins. KRAB-mediated repression requires
      binding to the KAP-1 corepressor, which in turn recruits members of the
      heterochromatin protein 1 (HP1) family. The HP1 proteins are nonhistone
      chromosomal proteins, although it is unclear how they are targeted to unique
      chromosomal domains or promoters. In this report, we have reconstituted and
      characterized the HP1-KAP-1 interaction using purified proteins and have compared
      KAP-1 to three other known HP1 binding proteins: SP100, lamin B receptor (LBR),
      and the p150 subunit from chromatin assembly factor (CAF-1 p150). We show that
      the chromoshadow domain (CSD) of HP1 is a potent repression domain that binds
      directly to all four previously described proteins. For KAP-1, we have mapped the
      CSD interaction region to a 15-amino-acid segment, termed the HP1BD, which is
      also present in CAF-1 p150 but not SP100 or LBR. The region of KAP-1 harboring
      the HP1BD binds as a monomer to a dimer of the CSD, as revealed by gel
      filtration, analytical ultracentrifugation, and optical biosensor analyses. The
      use of a spectrum of amino acid substitutions in the human HP1alpha CSD revealed
      a strong correlation between CSD-mediated repression and binding to KAP-1, CAF-1
      p150, and SP100 but not LBR. Differences among the HP1 binding partners could
      also be discerned by fusion to a heterologous DNA binding domain and by the
      potential to act as dominant negative molecules. Together, these results strongly
      suggest that KAP-1 is a physiologically relevant target for HP1 function.

PMID- 10938123
TI  - Structure and dynamic properties of a glucocorticoid receptor-induced chromatin
      transition.
AB  - Activation of the mouse mammary tumor virus (MMTV) promoter by the glucocorticoid
      receptor (GR) is associated with a chromatin structural transition in the B
      nucleosome region of the viral long terminal repeat (LTR). Recent evidence
      indicates that this transition extends upstream of the B nucleosome, encompassing
      a region larger than a single nucleosome (G. Fragoso, W. D. Pennie, S. John, and
      G. L. Hager, Mol. Cell. Biol. 18:3633-3644). We have reconstituted MMTV LTR DNA
      into a polynucleosome array using Drosophila embryo extracts. We show binding of
      purified GR to specific GR elements within a large, multinucleosome array and
      describe a GR-induced nucleoprotein transition that is dependent on ATP and a
      HeLa nuclear extract. Previously uncharacterized GR binding sites in the upstream
      C nucleosome region are involved in the extended region of chromatin remodeling.
      We also show that GR-dependent chromatin remodeling is a multistep process; in
      the absence of ATP, GR binds to multiple sites on the chromatin array and
      prevents restriction enzyme access to recognition sites. Upon addition of ATP, GR
      induces remodeling and a large increase in access to enzymes sites within the
      transition region. These findings suggest a dynamic model in which GR first binds
      to chromatin after ligand activation, recruits a remodeling activity, and is then
      lost from the template. This model is consistent with the recent description of a
      "hit-and-run" mechanism for GR action in living cells (J. G. McNally, W. G.
      Muller, D. Walker, and G. L. Hager, Science 287:1262-1264, 2000).

PMID- 10938124
TI  - The Rad51 paralog Rad51B promotes homologous recombinational repair.
AB  - The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role
      in both mitotic and meiotic homologous DNA recombination. Seven members of the
      Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and
      five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30%
      sequence identity with Rad51. In chicken B lymphocyte DT40 cells, we generated a
      mutant with RAD51B/RAD51L1, a member of the Rad51 family, knocked out. RAD51B(-/
      ) cells are viable, although spontaneous chromosomal aberrations kill about 20%
      of the cells in each cell cycle. Rad51B deficiency impairs homologous
      recombinational repair (HRR), as measured by targeted integration, sister
      chromatid exchange, and intragenic recombination at the immunoglobulin locus.
      RAD51B(-/-) cells are quite sensitive to the cross-linking agents cisplatin and
      mitomycin C and mildly sensitive to gamma-rays. The formation of damage-induced
      Rad51 nuclear foci is much reduced in RAD51B(-/-) cells, suggesting that Rad51B
      promotes the assembly of Rad51 nucleoprotein filaments during HRR. These findings
      show that Rad51B is important for repairing various types of DNA lesions and
      maintaining chromosome integrity.

PMID- 10938125
TI  - Human papillomavirus type 16 E7 oncoprotein binds and inactivates growth
      inhibitory insulin-like growth factor binding protein 3.
AB  - The E7 protein encoded by human papillomavirus type 16 is one of the few viral
      genes that can immortalize primary human cells and thereby override cellular
      senescence. While it is generally assumed that this property of E7 depends on its
      interaction with regulators of the cell cycle, we show here that E7 targets
      insulin-like growth factor binding protein 3 (IGFBP-3), the product of a p53
      inducible gene that is overexpressed in senescent cells. IGFBP-3 can suppress
      cell proliferation and induce apoptosis; we show here that IGFBP-3-mediated
      apoptosis is inhibited by E7, which binds to IGFBP-3 and triggers its proteolytic
      cleavage. Two transformation-deficient mutants of E7 failed to inactivate IGFBP
      3, suggesting that inactivation of IGFBP-3 may contribute to cell transformation.

PMID- 10938126
TI  - Targeted deletion of Minpp1 provides new insight into the activity of multiple
      inositol polyphosphate phosphatase in vivo.
AB  - Multiple inositol polyphosphate phosphatase (Minpp1) metabolizes inositol
      1,3,4,5,6-pentakisphosphate (InsP(5)) and inositol hexakisphosphate (InsP(6))
      with high affinity in vitro. However, Minpp1 is compartmentalized in the
      endoplasmic reticulum (ER) lumen, where access of enzyme to these predominantly
      cytosolic substrates in vivo has not previously been demonstrated. To gain
      insight into the physiological activity of Minpp1, Minpp1-deficient mice were
      generated by homologous recombination. Tissue extracts from Minpp1-deficient mice
      lacked detectable Minpp1 mRNA expression and Minpp1 enzyme activity.
      Unexpectedly, Minpp1-deficient mice were viable, fertile, and without obvious
      defects. Although Minpp1 expression is upregulated during chondrocyte
      hypertrophy, normal chondrocyte differentiation and bone development were
      observed in Minpp1-deficient mice. Biochemical analyses demonstrate that InsP(5)
      and InsP(6) are in vivo substrates for ER-based Minpp1, as levels of these
      polyphosphates in Minpp1-deficient embryonic fibroblasts were 30 to 45% higher
      than in wild-type cells. This increase was reversed by reintroducing exogenous
      Minpp1 into the ER. Thus, ER-based Minpp1 plays a significant role in the
      maintenance of steady-state levels of InsP(5) and InsP(6). These polyphosphates
      could be reduced below their natural levels by aberrant expression in the cytosol
      of a truncated Minpp1 lacking its ER-targeting N terminus. This was accompanied
      by slowed cellular proliferation, indicating that maintenance of cellular InsP(5)
      and InsP(6) is essential to normal cell growth. Yet, depletion of cellular
      inositol polyphosphates during erythropoiesis emerges as an additional
      physiological activity of Minpp1; loss of this enzyme activity in erythrocytes
      from Minpp1-deficient mice was accompanied by upregulation of a novel,
      substitutive inositol polyphosphate phosphatase.

PMID- 10938127
TI  - Phosphoenolpyruvate carboxykinase is necessary for the integration of hepatic
      energy metabolism.
AB  - We used an allelogenic Cre/loxP gene targeting strategy in mice to determine the
      role of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) in hepatic energy
      metabolism. Mice that lack this enzyme die within 3 days of birth, while mice
      with at least a 90% global reduction of PEPCK, or a liver-specific knockout of
      PEPCK, are viable. Surprisingly, in both cases these animals remain euglycemic
      after a 24-h fast. However, mice without hepatic PEPCK develop hepatic steatosis
      after fasting despite up-regulation of a variety of genes encoding free fatty
      acid-oxidizing enzymes. Also, marked alterations in the expression of hepatic
      genes involved in energy metabolism occur in the absence of any changes in plasma
      hormone concentrations. Given that a ninefold elevation of the hepatic malate
      concentration occurs in the liver-specific PEPCK knockout mice, we suggest that
      one or more intermediary metabolites may directly regulate expression of the
      affected genes. Thus, hepatic PEPCK may function more as an integrator of hepatic
      energy metabolism than as a determinant of gluconeogenesis.

PMID- 10938128
TI  - The SH3 domain directs acto-myosin-dependent targeting of v-Src to focal
      adhesions via phosphatidylinositol 3-kinase.
AB  - The v-Src oncoprotein is translocated to integrin-linked focal adhesions, where
      its tyrosine kinase activity induces adhesion disruption and cell transformation.
      We previously demonstrated that the intracellular targeting of Src is dependent
      on the actin cytoskeleton, under the control of the Rho family of small G
      proteins. However, the assembly of v-Src into focal adhesions does not require
      its catalytic activity or myristylation-dependent membrane association. Here, we
      report that the SH3 domain is essential for the assembly of focal adhesions
      containing the oncoprotein by mediating a switch from a microtubule-dependent,
      perinuclear localization to actin-associated focal adhesions; furthermore, v-Src
      translocation to focal adhesions requires myosin activity, at least under normal
      conditions when the actin cytoskeleton is being dynamically regulated. Although
      the SH3 domain of v-Src is also necessary for its association with focal adhesion
      kinase (FAK), which is often considered a likely candidate mediator of focal
      adhesion targeting via its carboxy-terminal targeting sequence, we show here that
      binding to FAK is not essential for the targeting of v-Src to focal adhesions.
      The p85 regulatory subunit of phosphatidylinositol (PI) 3-kinase also associates
      with v-Src in an SH3-dependent manner, but in this case inhibition of PI 3-kinase
      activity suppressed assembly of focal adhesions containing the oncoprotein. Thus,
      the Src SH3 domain, which binds PI 3-kinase and which is necessary for activation
      of Akt downstream, is required for the actin-dependent targeting of v-Src to
      focal adhesions.

PMID- 10938129
TI  - A bromodomain protein, MCAP, associates with mitotic chromosomes and affects G(2)
      to-M transition.
AB  - We describe a novel nuclear factor called mitotic chromosome-associated protein
      (MCAP), which belongs to the poorly understood BET subgroup of the bromodomain
      superfamily. Expression of the 200-kDa MCAP was linked to cell division, as it
      was induced by growth stimulation and repressed by growth inhibition. The most
      notable feature of MCAP was its association with chromosomes during mitosis,
      observed at a time when the majority of nuclear regulatory factors were released
      into the cytoplasm, coinciding with global cessation of transcription. Indicative
      of its predominant interaction with euchromatin, MCAP localized on mitotic
      chromosomes with exquisite specificity: (i) MCAP-chromosome association became
      evident subsequent to the initiation of histone H3 phosphorylation and early
      chromosomal condensation; and (ii) MCAP was absent from centromeres, the sites of
      heterochromatin. Supporting a role for MCAP in G(2)/M transition, microinjection
      of anti-MCAP antibody into HeLa cell nuclei completely inhibited the entry into
      mitosis, without abrogating the ongoing DNA replication. These results suggest
      that MCAP plays a role in a process governing chromosomal dynamics during
      mitosis.

PMID- 10938130
TI  - In-depth mutational analysis of the promyelocytic leukemia zinc finger BTB/POZ
      domain reveals motifs and residues required for biological and transcriptional
      functions.
AB  - The promyelocytic leukemia zinc finger (PLZF) protein is a transcription factor
      disrupted in patients with t(11;17)(q23;q21)-associated acute promyelocytic
      leukemia. PLZF contains an N-terminal BTB/POZ domain which is required for
      dimerization, transcriptional repression, formation of high-molecular-weight DNA
      protein complexes, nuclear sublocalization, and growth suppression. X-ray
      crystallographic data show that the PLZF BTB/POZ domain forms an obligate
      homodimer via an extensive interface. In addition, the dimer possesses several
      highly conserved features, including a charged pocket, a hydrophobic monomer
      core, an exposed hydrophobic surface on the floor of the dimer, and two
      negatively charged surface patches. To determine the role of these structures,
      mutational analysis of the BTB/POZ domain was performed. We found that point
      mutations in conserved residues that disrupt the dimer interface or the monomer
      core result in a misfolded nonfunctional protein. Mutation of key residues from
      the exposed hydrophobic surface suggests that these are also important for the
      stability of PLZF complexes. The integrity of the charged-pocket region was
      crucial for proper folding of the BTB/POZ domain. In addition, the pocket was
      critical for the ability of the BTB/POZ domain to repress transcription.
      Alteration of charged-pocket residue arginine 49 to a glutamine (mutant R49Q)
      yields a domain that can still dimerize but activates rather than represses
      transcription. In the context of full-length PLZF, a properly folded BTB/POZ
      domain was required for all PLZF functions. However, PLZF with the single pocket
      mutation R49Q repressed transcription, while the double mutant D35N/R49Q could
      not, despite its ability to dimerize. These results indicate that PLZF requires
      the BTB/POZ domain for dimerization and the charged pocket for transcriptional
      repression.

PMID- 10938131
TI  - Divergent N-terminal sequences target an inducible testis deubiquitinating enzyme
      to distinct subcellular structures.
AB  - Ubiquitin-specific processing proteases (UBPs) presently form the largest enzyme
      family in the ubiquitin system, characterized by a core region containing
      conserved motifs surrounded by divergent sequences, most commonly at the N
      terminal end. The functions of these divergent sequences remain unclear. We
      identified two isoforms of a novel testis-specific UBP, UBP-t1 and UBP-t2, which
      contain identical core regions but distinct N termini, thereby permitting
      dissection of the functions of these two regions. Both isoforms were germ cell
      specific and developmentally regulated. Immunocytochemistry revealed that UBP-t1
      was induced in step 16 to 19 spermatids while UBP-t2 was expressed in step 18 to
      19 spermatids. Immunoelectron microscopy showed that UBP-t1 was found in the
      nucleus while UBP-t2 was extranuclear and was found in residual bodies. For the
      first time, we show that the differential subcellular localization was due to the
      distinct N-terminal sequences. When transfected into COS-7 cells, the core region
      was expressed throughout the cell but the UBP-t1 and UBP-t2 isoforms were
      concentrated in the nucleus and the perinuclear region, respectively. Fusions of
      each N-terminal end with green fluorescent protein yielded the same subcellular
      localization as the native proteins, indicating that the N-terminal ends were
      sufficient for determining differential localization. Interestingly, UBP-t2
      colocalized with anti-gamma-tubulin immunoreactivity, indicating that like
      several other components of the ubiquitin system, a deubiquitinating enzyme is
      associated with the centrosome. Regulated expression and alternative N termini
      can confer specificity of UBP function by restricting its temporal and spatial
      loci of action.

PMID- 10938132
TI  - Retinoic acid regulation of Cdx1: an indirect mechanism for retinoids and
      vertebral specification.
AB  - Retinoic acid (RA) is required for diverse developmental programs, including
      vertebral specification. Both RA receptor disruption and excess RA result in
      homeotic transformations of the axial skeleton. These effects are believed to
      occur through altered expression of Hox genes, several of which have been
      demonstrated to be direct RA targets. Members of the cdx (caudal) homeobox gene
      family are also implicated in regulating Hox expression. Disruption of cdx1
      results in vertebral homeotic transformations and alteration of Hox expression
      boundaries; similar homeosis is also observed in cdx2 heterozygotes. In Xenopus,
      gain or loss of Cdx function affects vertebral morphogenesis through a mechanism
      that also correlates with altered Hox expression. Taken together with the finding
      of putative Cdx binding motifs in several Hox promoters, these data strongly
      support a role for Cdx members in direct regulation of expression of at least
      some Hox genes. Most retinoid-responsive Hox genes have not been demonstrated to
      be direct RA targets, suggesting that intermediaries are involved. Based on these
      findings, we hypothesized that one or more cdx members may transduce the effects
      of RA on Hox transcription. Consistent with this, we present evidence that cdx1
      is a direct RA target gene, suggesting an additional pathway for retinoid
      dependent vertebral specification.

PMID- 10938133
TI  - Associations and interactions between bare lymphocyte syndrome factors.
AB  - The bare lymphocyte syndrome, a severe combined immunodeficiency due to loss of
      major histocompatibility complex (MHC) class II gene expression, is caused by
      inherited mutations in the genes encoding the heterotrimeric transcription factor
      RFX (RFX-B, RFX5, and RFXAP) and the class II transactivator CIITA. Mutagenesis
      of the RFX genes was performed, and the properties of the proteins were analyzed
      with regard to transactivation, DNA binding, and protein-protein interactions.
      The results identified specific domains within each of the three RFX subunits
      that were necessary for RFX complex formation, including the ankyrin repeats of
      RFX-B. DNA binding was dependent on RFX complex formation, and transactivation
      was dependent on a region of RFX5. RFX5 was found to interact with CIITA, and
      this interaction was dependent on a proline-rich domain within RFX5. Thus, these
      studies have defined the protein domains required for the functional regulation
      of MHC class II genes.

PMID- 10938136
TI  - Limits to exhaustive exercise in fish.
AB  - Exercise to exhaustion leads to severe metabolic, acid-base and ionic changes in
      fish. It has been shown that several abiotic and biotic factors can limit burst
      exercise performance and the recovery process in fish. This article reviews the
      importance of body size, temperature, fasting/starvation and training on the
      ability of fish to perform and recover from exhaustive exercise. It is concluded
      that the constraints placed on a fish prior to and following exercise reflects
      the large intra-specific variability in the physiological response to exercise in
      fish.

PMID- 10938134
TI  - A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation
      and slow myosin heavy-chain expression.
AB  - The differentiation and maturation of skeletal muscle cells into functional
      fibers is coordinated largely by inductive signals which act through discrete
      intracellular signal transduction pathways. Recently, the calcium-activated
      phosphatase calcineurin (PP2B) and the family of transcription factors known as
      NFAT have been implicated in the regulation of myocyte hypertrophy and fiber type
      specificity. Here we present an analysis of the intracellular mechanisms which
      underlie myocyte differentiation and fiber type specificity due to an insulinlike
      growth factor 1 (IGF-1)-calcineurin-NFAT signal transduction pathway. We
      demonstrate that calcineurin enzymatic activity is transiently increased during
      the initiation of myogenic differentiation in cultured C2C12 cells and that this
      increase is associated with NFATc3 nuclear translocation. Adenovirus-mediated
      gene transfer of an activated calcineurin protein (AdCnA) potentiates C2C12 and
      Sol8 myocyte differentiation, while adenovirus-mediated gene transfer of
      noncompetitive calcineurin-inhibitory peptides (cain or DeltaAKAP79) attenuates
      differentiation. AdCnA infection was also sufficient to rescue myocyte
      differentiation in an IGF-depleted myoblast cell line. Using 10T1/2 cells, we
      demonstrate that MyoD-directed myogenesis is dramatically enhanced by either
      calcineurin or NFATc3 cotransfection, while a calcineurin inhibitory peptide
      (cain) blocks differentiation. Enhanced myogenic differentiation directed by
      calcineurin, but not NFATc3, preferentially specifies slow myosin heavy-chain
      expression, while enhanced differentiation through mitogen-activated protein
      kinase kinase 6 (MKK6) promotes fast myosin heavy-chain expression. These data
      indicate that a signaling pathway involving IGF-calcineurin-NFATc3 enhances
      myogenic differentiation whereas calcineurin acts through other factors to
      promote the slow fiber type program.

PMID- 10938137
TI  - Does immunointensity account for the differences in prognostic significance of
      Bcl-2 expression in non-small cell lung cancer?
AB  - Bcl-2 is an oncogenic protein that plays a central role in apoptosis. The
      association of Bcl-2 expression and prognosis in non-small cell lung cancer
      (NSCLC) is unclear, with some studies showing improved outcome whilst others show
      no survival advantage. We evaluated 178 surgically resected NSCLC specimens for
      Bcl-2 and p53 immunoexpression. Bcl-2 staining was present in 34.9% of cases
      (weakly staining 24.2%, strongly staining 10.7%), nuclear p53 in 43. 3% and
      cytoplasmic p53 in 10.7%. There was no association between p53 and survival. Bcl
      2 immunoexpression correlated with improved outcome (p=0.04). A sub-group of
      strongly Bcl-2 staining cases had a poor survival compared to those that stained
      weakly (p=0.01). The strongly staining cases had a similar survival to negative
      cases. Immunointensity may therefore account for the disparity in results
      regarding the prognostic significance of Bcl-2 demonstrated in previous studies.

PMID- 10938135
TI  - The SMRT corepressor is regulated by a MEK-1 kinase pathway: inhibition of
      corepressor function is associated with SMRT phosphorylation and nuclear export.
AB  - The SMRT (silencing mediator of retinoic acid and thyroid hormone receptor)
      corepressor participates in the repression of target gene expression by a variety
      of transcription factors, including the nuclear hormone receptors, promyelocytic
      leukemia zinc finger protein, and B-cell leukemia protein 6. The ability of SMRT
      to associate with these transcription factors and thereby to mediate repression
      is strongly inhibited by activation of tyrosine kinase signaling pathways, such
      as that represented by the epidermal growth factor receptor. We report here that
      SMRT function is potently inhibited by a mitogen-activated protein kinase (MAPK)
      kinase kinase (MAPKKK) cascade that operates downstream of this growth factor
      receptor. Intriguingly, the SMRT protein is a substrate for phosphorylation by
      protein kinases operating at multiple levels in this MAPKKK pathway, including
      the MAPKs, MAPK-extracellular signal-regulated kinase 1 (MEK-1), and MEK-1 kinase
      (MEKK-1). Phosphorylation of SMRT by MEKK-1 and, to a lesser extent, MEK-1
      inhibits the ability of SMRT to physically tether to its transcription factor
      partners. Notably, activation of MEKK-1 or MEK-1 signaling in transfected cells
      also leads to a redistribution of the SMRT protein from a nuclear compartment to
      a more perinuclear or cytoplasmic compartment. We suggest that SMRT-mediated
      repression is regulated by the MAPKKK cascade and that changes both in the
      affinity of SMRT for its transcription factors and in the subcellular
      distribution of SMRT contribute to the loss of SMRT function that is observed in
      response to kinase signal transduction.

PMID- 10938138
TI  - A new era of discovery in facial plastic surgery.
AB  - OBJECTIVE: To review recent advances in our understanding of molecular biology
      and wound healing relevant to facial plastic surgery. DATA SOURCES: Recent basic
      science literature relevant to molecular biology and wound healing and its
      clinical implications. CONCLUSIONS: During the 21st century, we will experience a
      new biological and informational age that will have profound implications for
      facial plastic surgery. This modern era will be driven by discoveries in
      molecular biology and wound healing that will result in new diagnosis and
      treatment modalities.

PMID- 10938140
TI  - Anatomic considerations in the management of the hanging columella

PMID- 10938139
TI  - Anatomical considerations in the management of the hanging columella.
AB  - OBJECTIVES: To review the anatomy and dynamics of the hanging columella and to
      describe a technique to correct the causative anatomical deformity. DESIGN: Case
      series. SETTING: A facial plastic surgery private practice in Highland Park, NJ.
      PATIENTS: Consecutive sample of 10 patients (6 women and 4 men), aged from 27 to
      52 years (mean age, 32 years). INTERVENTIONS: Through an external approach, the
      principal method of repair used in all cases involved transecting the medial and
      lateral crura at their angles to allow straightening of the medial crura. MAIN
      OUTCOME MEASURES: Comparative, standardized measurements of the alar-columellar
      complex in preoperative and postoperative photographs. RESULTS: Angle transection
      changed the spatial relation of the medial and lateral crura to each other
      resulting in straightening of the excessively curved medial crura. All patients
      had successful correction of the hanging columella. CONCLUSIONS: In our
      prospective study of 10 patients who required correction of hanging columellas,
      we have found the primary cause to be C-shaped curvature of the medial crura and
      their relation to the lateral crura. We observed long medial crura that were
      excessively curved, of normal width, and held in place by their continuity with
      the lateral crura. Dividing the alar cartilages at the angle of the medial and
      lateral crura released the connection of these structures allowing the medial
      crura to assume a straighter configuration. Tailoring of the feet of the medial
      crura and minimal septal shortening were occasionally used. Columellar struts,
      which were often used for other reasons, also provided additional medial crural
      straightening.

PMID- 10938141
TI  - Superior cantholysis for zygomatic fracture repair.
AB  - OBJECTIVE: To determine if performing a superior cantholysis eases the surgical
      exposure, reduction, and rigid fixation of the zygomaticofrontal suture in the
      open repair of zygomatic complex (ZMC) fractures. PATIENTS AND METHODS: Fifteen
      superior cantholysis procedures were used in 14 patients who presented with ZMC
      fractures requiring open reduction and internal fixation. Follow-up ranged from 6
      to 18 months. Collected data included patient demographics, cause of fracture,
      fracture classification, associated facial injuries, methods of fracture exposure
      and reduction, type and location of fixation, procedure-related complications,
      and postoperative outcome, including adequacy of fracture reduction. RESULTS:
      Superior cantholysis opens a direct surgical route to the zygomaticofrontal
      suture for exposure, reduction, and rigid fixation. It also expedites exposure
      and assessment of the sphenozygomatic suture. No postreduction ZMC malunions or
      malpositions occurred during the study. There were 4 complications, none of which
      could be attributed to superior cantholysis. The complications related primarily
      to the transconjunctival and lateral canthotomy incisions. CONCLUSIONS: Superior
      cantholysis eases the surgical exposure, reduction, and rigid fixation of the
      zygomaticofrontal suture in the open repair of ZMC fractures. The superior
      cantholysis added no morbidity in open ZMC fracture repair, and it simplified
      exposure of the lateral orbital rim, without the need for overzealous tissue
      retraction.

PMID- 10938142
TI  - Management of aggressive midface and orbital fibrous dysplasia.
AB  - OBJECTIVE: To discuss cosmetic and functional implications in the evaluation and
      treatment planning of large, aggressive midfacial fibrous dysplasias. PATIENTS
      AND METHODS: Eight patients (aged 2-38 years) with large fibrous dysplasias of
      the maxilla, zygomatic, and ethmoid bones requiring varying degrees of
      intervention and reconstruction were retrospectively reviewed. Patients with
      smaller lesions of these regions not requiring resection and reconstruction, as
      well those requiring sinus surgery alone were excluded from this review. RESULTS:
      All fibrous dysplasias in this review were monostotic, 6 originating in the
      maxilla, 1 in the zygoma, and 1 in the ethmoid. Five lesions (4 maxillary, 1
      zygomatic) caused cosmetic deformity without functional deficits and required
      resection and/or contouring only with minimal reconstruction. The remaining
      lesions were invasive such that function of the eye and/or dentition was
      affected. These lesions were treated by aggressive resection and various degrees
      of reconstruction to optimize function. CONCLUSIONS: While fibrous dyplasia is
      classified as a benign process, local expansion can cause significant functional
      and aesthetic deformities. Each lesion should be thoroughly evaluated and, when
      vital structures are involved or threatened, total or subtotal resection should
      be considered. A variety of options should be available to the surgeon for
      definitive primary reconstruction.

PMID- 10938143
TI  - Temporoparietal fascial flap in orbital reconstruction.
AB  - OBJECTIVE: To evaluate the success of the temporoparietal fascial flap (TPFF) in
      the primary or secondary reconstruction of difficult orbital defects and to
      review the surgical techniques. DESIGN: Retrospective analysis. SETTING: Tertiary
      medical center. PATIENTS: Nine patients with diverse orbital cavity or
      periorbital soft tissue and bony defects due to trauma, benign or malignant
      neoplasms, and radiation treatment. INTERVENTIONS: Temporoparietal fascial flap
      anatomy and techniques of harvest and inset are reviewed in detail. Four cases
      are presented to illustrate possible variables in orbital reconstruction.
      Variables examined include the location of defects, the success of flap survival
      in orbital cavities after primary or secondary reconstruction, the effects of
      prior irradiation on flap survival, and the possibility of concurrent
      osteointegrated implant placement with TPFF reconstruction. MAIN OUTCOME
      MEASURES: Functional and aesthetic outcomes were determined by physical
      examination and preoperative and postoperative photographs. RESULTS: All patients
      had successful transfer of TPFF grafts without flap compromise. Temporoparietal
      fascial flap was a viable option for subtle orbital and malar contour defects. In
      chronically inflamed wounds such as with osteoradionecrosis and orbitoantral
      fistula, TPFF successfully restored vascularity, obliterated the defects, and
      enabled the placement of osteointegrated implants. The TPFF also supported the
      concurrent placement of a free calvarial bone graft. Finally, split-thickness
      skin grafted onto a pedicled TPFF showed 100% survival. CONCLUSIONS: The TPFF is
      one of the most reliable and versatile regional flaps in the head and neck for
      orbital reconstruction. This study presents the use of TPFF in a variety of
      orbital defects, from lateral bony rim defects to total exenteration. Timing of
      repair in this study spans from immediate reconstruction to reconstruction
      delayed more than 50 years after the initial injury. In all cases, reconstruction
      with TPFF resulted in improved bony and soft tissue contours, and incurred
      minimal morbidity.

PMID- 10938144
TI  - The subgaleal endoscopic browlift.
AB  - Most endoscopic browlifts are performed in a subperiosteal plane with or without
      fixation posterior to the hairline at the incision site. The extent and longevity
      of browlifting are variable and somewhat unpredictable. We reviewed the
      literature on endoscopic browlifting techniques and describe herein our technique
      for the subgaleal endoscopic browlift procedure. It differs from the published
      reports of subperiosteal endoscopic techniques in the plane of dissection,
      circumvention of a periosteal release, and suture fixation at the brow level. We
      have used this technique for browlifting in male and female patients alike, as
      well as in patients with preoperative brow asymmetries, with consistent results.

PMID- 10938145
TI  - Bipolar scissors in facial plastic surgery.
AB  - BACKGROUND: Many methods are available to the facial plastic surgeon for
      elevating and separating tissue, from cold steel to monopolar cautery to various
      laser-cutting technologies. Bipolar cautery has replaced monopolar cautery as the
      optimal hemostatic technique because of its decreased tissue damage and improved
      capabilities. Bipolar scissors concurrently offer a dissecting technique with
      hemostatic capability. Little exists in the otolaryngology literature on the use
      of bipolar scissors for soft tissue dissection. OBJECTIVE: To describe our
      experience using bipolar scissors in a variety of facial plastic and
      reconstructive procedures. SETTING: Tertiary care referral academic center.
      DESIGN: We retrospectively reviewed 78 procedures performed using bipolar
      scissors between June 1997 and August 1999. In facial plastic cosmetic surgery,
      bipolar scissors were used 31 times for deep plane face-lifts and 16 times for
      endoscopic browlifts. In facial plastic reconstructive surgery, bipolar scissors
      were used in 15 radial forearm free flaps, 10 fibula osteocutaneous flaps, 3
      rectus abdominis free flaps, and 3 latissimus dorsi myocutaneous free flaps.
      RESULTS: In all procedures, bipolar scissors facilitated the dissection. By
      allowing for a drier field, less time was required to elevate the flap and obtain
      hemostasis. Complications were not increased compared with historical controls.
      In the harvesting of fibula osteocutaneous free flaps, use of bipolar scissors
      allowed harvesting without use of a tourniquet. CONCLUSION: Bipolar scissors, a
      new technology in facial plastic surgery, allow the same control as sharp
      dissection and provide simultaneous hemostasis.

PMID- 10938146
TI  - Experiences with transconjunctival upper blepharoplasty.
AB  - Upper blepharoplasty remains a valuable procedure in rejuvenating the upper
      eyelid. An innovative technique was recently reported whereby medial fat is
      removed through a transconjunctival approach. This is a preliminary report of our
      experience with 60 patients treated over the past 10 months using this technique.
      The technique will be described in detail and cases will be reported. There were
      no perioperative or postoperative complications. All of the patients are
      satisfied with the results of their surgical procedure. The technique has the
      advantage of avoiding an incision of the medial upper eyelid and the inherent
      risks of excessive scarring in this area. We have found the technique especially
      useful in secondary blepharoplasty with an isolated prominence of residual medial
      fat. Other advantages include the following: primary cases in which the surgeon
      is able to avoid medial extension of the cutaneous incision, patients who possess
      deep tarsal folds with prominent medial fat, or as an adjunct to eyebrow lifting
      techniques where in both cases cutaneous excision is unnecessary. No
      disadvantages have been noted.

PMID- 10938147
TI  - Treating the caudal septal deflection.
AB  - Caudal septal deflection can be a challenging nasal deformity. Although there are
      a number of maneuvers available to manage this functional and aesthetic
      abnormality, each approach is effective in only a limited number of cases. For
      over 25 years, the senior author (N.J.P.) has employed a "modified swinging door"
      technique for treatment of the deviated caudal septum. Using this technique, the
      septal cartilage along the maxillary crest is dissected free but is not excised.
      Instead, the caudal septum is flipped over the nasal spine, which acts as a
      "doorstop" and secures the caudal septum in a straighter position. This maneuver
      may be useful in the armamentarium of the surgeon managing this potentially
      difficult technical challenge.

PMID- 10938148
TI  - The flipper osteotome.

PMID- 10938150
TI  - Beauty: Ingres' odalisque: idealized beauty

PMID- 10938149
TI  - Malar augmentation with self-drilling single-screw fixation.
AB  - Augmentation with malar implants has traditionally relied on fixation techniques
      such as creation of a precise pocket, external taping, and transcutaneous
      fixation techniques with bolsters. We present an alternate technique that fixates
      the implants to the rigid facial skeleton rather than to the dynamic active
      facial soft tissues. To avoid the use of expensive drills, we describe use of
      self-drilling screws for fixation of malar implants. The technique avoids
      transconjunctival incisions, allows wide exposure, and is presented as an
      alternative to traditional fixation techniques.

PMID- 10938152
TI  - JAMA 100 years ago: EXPERIMENTATION ON THE CORD AFTER DECAPITATION

PMID- 10938151
TI  - Ten e-pistles for the e-fficient trimillennial physician.

PMID- 10938153
TI  - Where the elite meet to eat--a CME course?

PMID- 10938154
TI  - Global network fights a rounder population.

PMID- 10938156
TI  - Health agencies update: transplant therapy for diabetes

PMID- 10938155
TI  - Learning surgery online in Ireland.

PMID- 10938158
TI  - Health agencies update: snuffing the urge to smoke

PMID- 10938157
TI  - Health agencies update: lung disease gene identified

PMID- 10938159
TI  - Health agencies update: HIV prevention trials network

PMID- 10938160
TI  - The past and future of medical malpractice litigation.

PMID- 10938161
TI  - The past and future of medical malpractice litigation.

PMID- 10938163
TI  - The past and future of medical malpractice litigation

PMID- 10938162
TI  - The past and future of medical malpractice litigation.

PMID- 10938164
TI  - The past and future of medical malpractice litigation

PMID- 10938165
TI  - Managed care insurance and use of higher-mortality hospitals.

PMID- 10938166
TI  - Managed care insurance and use of higher-mortality hospitals.

PMID- 10938168
TI  - Managed care insurance and use of higher-mortality hospitals

PMID- 10938167
TI  - Managed care insurance and use of higher-mortality hospitals.

PMID- 10938169
TI  - Garlic as an insect repellent.

PMID- 10938170
TI  - Evidence of myocardial infarction in mummified human tissue.

PMID- 10938171
TI  - Cerebral hemorrhage following a roller coaster ride.

PMID- 10938172
TI  - The TIMI risk score for unstable angina/non-ST elevation MI: A method for
      prognostication and therapeutic decision making.
AB  - CONTEXT: Patients with unstable angina/non-ST-segment elevation myocardial
      infarction (MI) (UA/NSTEMI) present with a wide spectrum of risk for death and
      cardiac ischemic events. OBJECTIVE: To develop a simple risk score that has broad
      applicability, is easily calculated at patient presentation, does not require a
      computer, and identifies patients with different responses to treatments for
      UA/NSTEMI. DESIGN, SETTING, AND PATIENTS: Two phase 3, international, randomized,
      double-blind trials (the Thrombolysis in Myocardial Infarction [TIMI] 11B trial
      [August 1996-March 1998] and the Efficacy and Safety of Subcutaneous Enoxaparin
      in Unstable Angina and Non-Q-Wave MI trial [ESSENCE; October 1994-May 1996]). A
      total of 1957 patients with UA/NSTEMI were assigned to receive unfractionated
      heparin (test cohort) and 1953 to receive enoxaparin in TIMI 11B; 1564 and 1607
      were assigned respectively in ESSENCE. The 3 validation cohorts were the
      unfractionated heparin group from ESSENCE and both enoxaparin groups. MAIN
      OUTCOME MEASURES: The TIMI risk score was derived in the test cohort by selection
      of independent prognostic variables using multivariate logistic regression,
      assignment of value of 1 when a factor was present and 0 when it was absent, and
      summing the number of factors present to categorize patients into risk strata.
      Relative differences in response to therapeutic interventions were determined by
      comparing the slopes of the rates of events with increasing score in treatment
      groups and by testing for an interaction between risk score and treatment.
      Outcomes were TIMI risk score for developing at least 1 component of the primary
      end point (all-cause mortality, new or recurrent MI, or severe recurrent ischemia
      requiring urgent revascularization) through 14 days after randomization. RESULTS:
      The 7 TIMI risk score predictor variables were age 65 years or older, at least 3
      risk factors for coronary artery disease, prior coronary stenosis of 50% or more,
      ST-segment deviation on electrocardiogram at presentation, at least 2 anginal
      events in prior 24 hours, use of aspirin in prior 7 days, and elevated serum
      cardiac markers. Event rates increased significantly as the TIMI risk score
      increased in the test cohort in TIMI 11B: 4.7% for a score of 0/1; 8.3% for 2;
      13. 2% for 3; 19.9% for 4; 26.2% for 5; and 40.9% for 6/7 (P<.001 by chi(2) for
      trend). The pattern of increasing event rates with increasing TIMI risk score was
      confirmed in all 3 validation groups (P<.001). The slope of the increase in event
      rates with increasing numbers of risk factors was significantly lower in the
      enoxaparin groups in both TIMI 11B (P =.01) and ESSENCE (P =.03) and there was a
      significant interaction between TIMI risk score and treatment (P =. 02).
      CONCLUSIONS: In patients with UA/NSTEMI, the TIMI risk score is a simple
      prognostication scheme that categorizes a patient's risk of death and ischemic
      events and provides a basis for therapeutic decision making. JAMA. 2000;284:835
      842

PMID- 10938173
TI  - The contribution of mild and moderate preterm birth to infant mortality. Fetal
      and Infant Health Study Group of the Canadian Perinatal Surveillance System.
AB  - CONTEXT: The World Health Organization defines preterm birth as birth at less
      than 37 completed gestational weeks, but most studies have focused on very
      preterm infants (birth at <32 weeks) because of their high risk of mortality and
      serious morbidity. However, infants born at 32 through 36 weeks are more common
      and their public health impact has not been well studied. OBJECTIVE: To assess
      the quantitative contribution of mild (birth at 34-36 gestational weeks) and
      moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality.
      DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study using linked
      singleton live birth-infant death cohort files for US birth cohorts for 1985 and
      1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994.
      MAIN OUTCOME MEASURES: Relative risks (RRs) and etiologic fractions (EFs) for
      overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27
      days), postneonatal (age 28-364 days), and total infant death among mild and
      moderate preterm births vs term births (at >/=37 gestational weeks). RESULTS:
      Relative risks for infant death from all causes among singletons born at 32
      through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in
      the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994;
      among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95%
      CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2%
      and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%,
      respectively, at 34 through 36 gestational weeks; the sum of the EFs for births
      at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at
      28 through 31 gestational weeks. Substantial RRs were observed overall for the
      neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian
      infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2%
      for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0
      7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks;
      EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for
      death due to asphyxia, infection, sudden infant death syndrome, and external
      causes. Except for a reduction in the RR and EF for neonatal mortality due to
      infection, the patterns have changed little since 1985 in either country.
      CONCLUSIONS: Mild- and moderate-preterm birth infants are at high RR for death
      during infancy and are responsible for an important fraction of infant deaths.
      JAMA. 2000;284:843-849

PMID- 10938174
TI  - Cost-utility analysis of the cochlear implant in children.
AB  - CONTEXT: Barriers to the use of cochlear implants in children with profound
      deafness include device costs, difficulty assessing benefit, and lack of data to
      compare the implant with other medical interventions. OBJECTIVE: To determine the
      quality of life and cost consequences for deaf children who receive a cochlear
      implant. DESIGN: Cost-utility analysis using preintervention, postintervention,
      and cross-sectional surveys conducted from July 1998 to May 2000. SETTING:
      Hearing clinic at a US academic medical center. PARTICIPANTS: Parents of 78
      profoundly deaf children (average age, 7.5 years) who received cochlear implants.
      MAIN OUTCOME MEASURES: Direct and total cost to society per quality-adjusted life
      year (QALY) using the time-trade-off (TTO), visual analog scale (VAS), and Health
      Utilities Index-Mark III (HUI), discounting costs and benefits 3% annually.
      Parents rated their child's health state at the time of the survey and
      immediately before and 1 year before implantation. RESULTS: Recipients had an
      average of 1.9 years of implant use. Mean VAS scores increased by 0. 27, from
      0.59 before implantation to 0.86 at survey. In a subset of participants, TTO
      scores increased by 0.22, from 0.75 to 0.97 (n = 40) and HUI scores increased by
      0.39, from 0.25 to 0.64 (n = 22). Quality-of-life scores were no different 1 year
      before and immediately before implantation. Discounted direct costs were $60,228,
      yielding $9,029 per QALY using the TTO, $7,500 per QALY using the VAS, and $5,197
      per QALY using the HUI. Including indirect costs such as reduced educational
      expenses, the cochlear implant provided a savings of $53,198 per child.
      CONCLUSIONS: Cochlear implants in profoundly deaf children have a positive effect
      on quality of life at reasonable direct costs and appear to result in a net
      savings to society. JAMA. 2000;284:850-856

PMID- 10938175
TI  - Phenotypic characteristics associated with the APC gene I1307K mutation in
      Ashkenazi Jewish patients with colorectal polyps.
AB  - CONTEXT: The I1307K mutation of the APC gene is found in approximately 6% of the
      Ashkenazi Jewish population and is associated with elevated risk of colorectal
      cancer. The incidence of the mutation in patients with colorectal adenomas is
      unknown. OBJECTIVES: To determine the carrier rate of the I1307K mutation in
      Ashkenazi Jewish patients with a history of colorectal polyps but without
      colorectal cancer and to compare phenotypic characteristics and family history of
      carriers vs noncarriers. DESIGN, SETTING, AND PATIENTS: A total of 231 patients
      who had at least 1 large bowel polyp diagnosed between January 1, 1992, and
      January 31, 1999, at 1 of 5 centers in Boston, Mass, were included, of whom 183
      were Ashkenazi Jewish. DNA was isolated from cheek swab samples. MAIN OUTCOME
      MEASURES: Presence of the I1307K variant in the APC gene. RESULTS: The I1307K
      variant was identified in 22 (14%) of 161 Ashkenazi Jewish patients with a
      history of adenomatous polyps and in 1 (5%) of 20 Ashkenazi Jewish patients with
      hyperplastic polyps. The phenotypic features of adenomas, family history of
      polyps, colorectal cancer, and other cancers were indistinguishable between
      I1307K carriers and noncarriers. CONCLUSIONS: The frequency of the APC I1307K
      mutation is elevated in Ashkenazi Jewish patients with adenomatous polyps, but
      not hyperplastic polyps. The I1307K mutation represents a novel paradigm for
      cancer-predisposing genes, as it is associated with moderately increased risk of
      neoplasia without other associated distinguishing phenotypic features. JAMA.
      2000;284:857-860

PMID- 10938176
TI  - Age-related changes in slow wave sleep and REM sleep and relationship with growth
      hormone and cortisol levels in healthy men.
AB  - CONTEXT: In young adults, sleep affects the regulation of growth hormone (GH) and
      cortisol. The relationship between decreased sleep quality in older adults and
      age-related changes in the regulation of GH and cortisol is unknown. OBJECTIVE:
      To determine the chronology of age-related changes in sleep duration and quality
      (sleep stages) in healthy men and whether concomitant alterations occur in GH and
      cortisol levels. DESIGN AND SETTING: Data combined from a series of studies
      conducted between 1985 and 1999 at 4 laboratories. SUBJECTS: A total of 149
      healthy men, aged 16 to 83 years, with a mean (SD) body mass index of 24.1 (2.3)
      kg/m( 2), without sleep complaints or histories of endocrine, psychiatric, or
      sleep disorders. MAIN OUTCOME MEASURES: Twenty-four-hour profiles of plasma GH
      and cortisol levels and polygraphic sleep recordings. RESULTS: The mean (SEM)
      percentage of deep slow wave sleep decreased from 18.9% (1.3%) during early
      adulthood (age 16-25 years) to 3.4% (1.0%) during midlife (age 36-50 years) and
      was replaced by lighter sleep (stages 1 and 2) without significant increases in
      sleep fragmentation or decreases in rapid eye movement (REM) sleep. The
      transition from midlife to late life (age 71-83 years) involved no further
      significant decrease in slow wave sleep but an increase in time awake of 28
      minutes per decade at the expense of decreases in both light non-REM sleep (-24
      minutes per decade; P<.001) and REM sleep (-10 minutes per decade; P<.001). The
      decline in slow wave sleep from early adulthood to midlife was paralleled by a
      major decline in GH secretion (-372 microg per decade; P<.001). From midlife to
      late life, GH secretion further declined at a slower rate (-43 microg per decade;
      P<.02). Independently of age, the amount of GH secretion was significantly
      associated with slow wave sleep (P<.001). Increasing age was associated with an
      elevation of evening cortisol levels (+19. 3 nmol/L per decade; P<.001) that
      became significant only after age 50 years, when sleep became more fragmented and
      REM sleep declined. A trend for an association between lower amounts of REM sleep
      and higher evening cortisol concentrations independent of age was detected
      (P<.10). CONCLUSIONS: In men, age-related changes in slow wave sleep and REM
      sleep occur with markedly different chronologies and are each associated with
      specific hormonal alterations. Future studies should evaluate whether strategies
      to enhance sleep quality may have beneficial hormonal effects. JAMA. 2000;284:861
      868

PMID- 10938177
TI  - Users' guides to the medical literature: XXIV. How to use an article on the
      clinical manifestations of disease. Evidence-Based Medicine Working Group.
AB  - Clinicians rely on knowledge about the clinical manifestations of disease to make
      clinical diagnoses. Before using research on the frequency of clinical features
      found in patients with a disease, clinicians should appraise the evidence for its
      validity, results, and applicability. For validity, 4 issues are important-how
      the diagnoses were verified, how the study sample relates to all patients with
      the disease, how the clinical findings were sought, and how the clinical findings
      were characterized. Ideally, investigators will verify the presence of disease in
      study patients using credible criteria that are independent of the clinical
      manifestations under study. Also, ideally the study patients will represent the
      full spectrum of the disease, undergo a thorough and consistent search for
      clinical findings, and these findings will be well characterized in nature and
      timing. The main results of these studies are expressed as the number and
      percentages of patients with each manifestation. Confidence intervals can
      describe the precision of these frequencies. Most clinical findings occur with
      only intermediate frequency, and since these frequencies are equivalent to
      diagnostic sensitivities, this means that the absence of a single finding is
      rarely powerful enough to exclude the disease. Before acting on the evidence,
      clinicians should consider whether it applies to their own patients and whether
      it has been superseded by new developments. Detailed knowledge of the clinical
      manifestations of disease should increase clinicians' ability to raise diagnostic
      hypotheses, select differential diagnoses, and verify final diagnoses. JAMA.
      2000;284:869-875

PMID- 10938178
TI  - Risk stratification and therapeutic decision making in acute coronary syndromes.

PMID- 10938179
TI  - Age-related alterations in sleep quality and neuroendocrine function:
      interrelationships and implications.

PMID- 10938180
TI  - Is routine screening for melanoma a benign practice?

PMID- 10938181
TI  - Early detection of melanoma.

PMID- 10938182
TI  - The contribution of neurophysiology to the diagnosis of leptomeningeal
      metastases.

PMID- 10938183
TI  - Prevention of recurrent stroke.
AB  - There is a considerable knowledge about risk factors for first ever stroke and a
      lack of knowledge about risk factors for recurrent stroke. As neurologists we
      rarely see the patient before the first transient ischemic attack (TIA) or
      stroke, and we are concerned with and need data on secondary stroke prevention.
      For lifestyle factors such as cigarette smoking, physical activity and alcohol
      consumption, data are scarce. For post-menopausal estrogen use there are no data
      on risk of recurrent stroke. Plasma homocysteine has emerged as a risk factor for
      stroke and cardiovascular disease. It is not yet documented if supplementation of
      folic acid, which may reduce plasma homocysteine, also lowers risk of stroke.
      Elevated blood pressure is a risk factor for recurrent stroke. There are four
      randomized trials of antihypertensive treatment after stroke indicating a
      tendency of reduced risk of stroke recurrence. Three studies of antihypertensive
      treatment after first stroke are in progress. Prevention of recurrent stroke is
      well documented in atrial fibrillation where warfarin is highly beneficial and
      aspirin has some effect. Carotid endarterectomy in high grade carotid artery
      stenosis is also well documented. Antiplatelet therapy provides secondary
      prevention in most types of ischemic brain disease.

PMID- 10938184
TI  - Does abnormal neuronal excitability exist in myotonic dystrophy? I. Effects of
      the antiarrhythmic drug hydroquinidine on slow saccadic eye movements.
AB  - The abnormal neuronal excitability hypothesized in myotonic dystrophy (MD) might
      contribute to psychomotor and behavioral disturbances of MD patients. To gain new
      insights into the pathophysiology of MD, we determined whether the antiarrhythmic
      drug hydroquinidine would ameliorate slow saccadic eye movements (SEMs), apathy
      and hypersomnia in MD patients. SEMs were selected as simple modality for
      psychomotor investigation. The study was conducted in a randomized, placebo
      controlled, double-blind, crossover manner. Ten ambulatory patients without
      contraindications to hydroquinidine administration were enrolled. Hydroquinidine
      (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6
      weeks between treatments. SEMs were recorded by electrooculography and analyzed
      by a computer system. Two patients withdrew in the first week of active treatment
      because of nausea and epigastralgia. Hydroquinidine significantly increased the
      normalized peak saccadic velocity and shortened the saccadic reaction time
      compared to placebo. The drug's effects on apathy and hypersomnia are presented
      in a companion paper.

PMID- 10938185
TI  - Does abnormal neuronal excitability exist in myotonic dystrophy? II. Effects of
      the antiarrhythmic drug hydroquinidine on apathy and hypersomnia.
AB  - An abnormal neuronal excitability in myotonic dystrophy (MD) might contribute to
      psychomotor and behavioral disturbances of MD patients. To gain new insights into
      the pathophysiology of MD, we determined whether the antiarrhythmic drug
      hydroquinidine could ameliorate apathy and hypersomnia besides slow saccadic eye
      movements in these patients. The study was conducted in a randomized, placebo
      controlled, double-blind, crossover manner. Ten ambulatory patients without
      contraindications to hydroquinidine administration were enrolled. Hydroquinidine
      (450 mg/day) or placebo was given orally for 6 weeks with a washout period of 6
      weeks between treatments. Apathy was evaluated by means of the apathy evaluation
      scale (AES) and hypersomnia by a sleep diary. Two patients withdrew in the first
      week of active treatment because of nausea and epigastralgia. The drug
      significantly reduced AES scores and daily sleep time compared to placebo. Thus,
      hydroquinidine can ameliorate apathy and hypersomnia in MD. However, the
      possibility of proarrhythmia and the high frequency of cardiac disturbances in MD
      seriously limit the therapeutic perspective. The effects on eye movements are
      presented in a companion paper.

PMID- 10938186
TI  - Long-term immunological changes in azathioprine-treated MS patients.
AB  - The long-term immunological effects of azathioprine treatment have been
      investigated in 8 multiple sclerosis patients with different course of disease,
      chronic progressive (CP) or relapsing progressive (RP). We studied fluctuations
      in peripheral blood mononuclear cell subsets, IgG, IgM and soluble vascular cell
      adhesion molecule-1 (sVCAM-1), before and after 2 (T24) and 3 (T36) years of
      therapy. We observed a significant decrease in CD8+ cells over time and a trend
      to lower percentage of CD3-CD56+ cells at T24 and T36. CD4+CD45RA+ cells in MS
      patients were lower than in healthy controls before therapy and reached values
      similar to those of healthy controls at T24 and T36. The remaining immunological
      parameters did not show any significant fluctuations.

PMID- 10938187
TI  - The SMile Card: a computerised data card for multiple sclerosis patients. SMile
      Card Scientific Board.
AB  - The SMile Card was developed as a means for computerising clinical information
      for the purpose of transferability, accessibility, standardisation and
      compilation of a national database of demographic and clinical information about
      multiple sclerosis (MS) patients. In many European countries, centres for MS are
      organised independently from one another making collaboration, consultation and
      patient referral complicated. Only the more highly advanced clinical centres,
      generally located in large urban areas, have had the possibility to utilise
      technical possibilities for improving the organisation of patient clinical and
      research information, although independently from other centres. The information
      system, developed utilising the Visual Basic language for Microsoft Windows 95,
      stores information via a 'smart card' in a database which is initiated and
      updated utilising a microprocessor, located at each neurological clinic. The
      SMile Card, currently being tested in Italy, permits patients to carry with them
      all relevant medical information without limitations. Neurologists are able to
      access and update, via the microprocessor, the patient's entire medical history
      and MS-related information, including the complete neurological examination and
      laboratory test results. The SMile Card provides MS patients and neurologists
      with a complete computerised archive of clinical information which is accessible
      throughout the country. In addition, data from the SMile Card system can be
      exported to other database programs.

PMID- 10938189
TI  - Clinical, biochemical and neuroradiological findings in L-2-hydroxyglutaric
      aciduria.
AB  - L-2-Hydroxyglutaric aciduria is a rare inborn error of metabolism, marked by a
      large and persistent increase of L-2-hydroxyglutaric acid in urine, blood and
      cerebrospinal fluid (CSF). We present clinical, biochemical and neuroradiological
      findings of seven Italian patients aged 4-19 years presenting at different stages
      of the disease. The disorder was characterized by a progressive neurological
      syndrome with cerebellar and pyramidal signs, mental deterioration, epilepsy and
      subcortical leukoencephalopathy on magnetic resonance imaging (MRI). We observed
      a good correlation between the severity of the disease and the extent of lesions
      on MRI. We report the result of the first positive prenatal diagnosis.

PMID- 10938188
TI  - An Italian family with autosomal recessive quadriceps-sparing inclusion-body
      myopathy (ARQS-IBM) linked to chromosome 9p1.
AB  - We report an Italian family with autosomal recessive quadriceps-sparing inclusion
      body myopathy (ARQS-IBM). The patients (two second cousins) developed a slowly
      progressive distal and proximal myopathy with complete sparing of the quadriceps.
      Muscle biopsy showed rimmed vacuoles in numerous muscle fibers, and electron
      microscopy documented accumulation of 15-21 nm filaments. DNA analysis
      established linkage to 9p1 and haplotype analysis revealed that the patients
      shared a recombined common haplotype. The gene locus of ARQS-IBM was initially
      mapped to chromosome 9p1-q1 in families of Iranian-Jewish origin and later
      confirmed in a few other ethnic groups. This is the first report of Italian
      patients with ARQS-IBM showing positive linkage to chromosome 9p1. Our data
      suggest that patients having distal and proximal myopathy with rimmed vacuoles
      and possible recessive inheritance, often classified as distal myopathies, should
      be thoroughly investigated according to the diagnostic criteria of h-IBM and,
      when positive, studied for linkage to chromosome 9p1.

PMID- 10938191
TI  - Multiple radiculopathy of the lower limbs in a cancer patient with meningeal
      carcinomatosis.
AB  - Meningeal carcinomatosis occurs in 1%-5% of patients with breast cancer. Early
      diagnosis and aggressive treatment of neurologic involvement are important
      factors of prognosis. We report a case of a 52-year-old woman who was affected by
      bilateral breast carcinoma treated with surgery and chemotherapy. Six years after
      she had become asymptomatic, X-rays showed lumbar spine metastases which were
      treated with radiotherapy. After 1 year she began to suffer from lower limb
      paresthesias, unsteadiness and unstable gait. Clinical examination showed lower
      limb sensory ataxia with lack of knee and ankle reflexes, and hypopallesthesia
      from the iliac spine to the foot. Spinal magnetic resonance imaging (MRI) with
      contrast agent revealed no medullar compression. Electromyography disclosed
      bilateral involvement of L4-L5-S1 roots and corresponding paraspinal muscles.
      Sensory and motor conductions were normal. Cerebrospinal fluid (CSF) examination
      showed the presence of neoplastic cells, confirming the diagnosis of meningeal
      carcinomatosis. Our patient underwent 9 cycles of intrathecal methotrexate
      therapy (25 mg/cycle) with improvement of ataxia and relief of paresthesias. One
      year later, CSF examination is still negative. We point out the importance of
      electrodiagnostic studies and CSF examination in the early documentation of root
      involvement in cancer patients, when computed tomography, MRI and myelography are
      normal. Early diagnosis may lead to effective therapy which prolongs survival.

PMID- 10938190
TI  - A new de novo mutation of the connexin-32 gene in a patient with X-linked Charcot
      Marie-Tooth type 1 disease.
AB  - We report a 26-year-old Italian man with X-linked Charcot-Marie-Tooth (CMT)
      disease type 1 (CMT-X1) and a negative family history for neuromuscular diseases.
      Clinical and electrophysiological examinations of the patient's mother and
      siblings were normal. Molecular analysis by polymerase chain reaction--single
      strand conformation polymorphism (PCR-SSCP) on genomic DNA from the patient and
      all members of his family revealed a C-to-T transition in codon 8 of exon 2 of
      the connexin-32 (Cx32) gene on the X chromosome only in the patient. This
      transition in the 5'-coding region, resulting in a Thr-Ile substitution, is
      likely to be the cause of CMT phenotype in our patient, and it represents a new
      de novo mutation of the Cx32 gene.

PMID- 10938192
TI  - Therapeutic effectiveness of acetazolamide in hindbrain hernia headache.
AB  - A 43-year-old man had been suffering from exertional headache for 10 years.
      Sagittal sections on magnetic resonance imaging showed a Chiari type 1
      malformation and a cerebellar arachnoid cyst. This syndrome, named hindbrain
      hernia headache, disappeared with oral acetazolamide. This treatment should be
      tried in patients with hindbrain hernia headache prior to considering surgical
      decompression of the foramen magnum.

PMID- 10938193
TI  - Risperidone in idiopathic and symptomatic dystonia: preliminary experience.
AB  - Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic
      (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of
      risperidone in the treatment of idiopathic and symptomatic dystonias in seven
      patients using the Fahn and Marsden rating scale for torsion dystonia before and
      after four weeks of treatment (2-6 mg/day). The twisting and involuntary
      movements with abnormal postures decreased in all the patients treated, with a
      statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results
      suggest that risperidone is useful in idiopathic and symptomatic dystonia.

PMID- 10938194
TI  - Myoglobinuria after ingestion of extracts of guarana, Ginkgo biloba and kava.

PMID- 10938195
TI  - Challenges for clinical neurophysiology.

PMID- 10938196
TI  - The Italian Guidelines for stroke prevention. The Stroke Prevention and
      Educational Awareness Diffusion (SPREAD) Collaboration.

PMID- 10938197
TI  - Temporal trends of stroke in Valle d'Aosta, Italy. Incidence and 30-day fatality
      rates.
AB  - The objective of this study was to evaluate temporal changes of stroke in an
      Italian community by comparing the present incidence rates with those reported in
      the same area for 1989. The two studies were conducted by the same research group
      and met almost all the criteria proposed for an "ideal" stroke incidence study.
      The annual incidence rate per 1000 inhabitants increased (p < 0.01) by 29%, from
      2.23 (95% CL, 1.96-2.50) in 1989 to 2.89 (95% CL, 2.58-3.20) in 1997. No
      statistically significant change was found when these rates were adjusted to the
      1991 Italian population. The overall incidence rate was 2.40 (95% CL, 2.14-2.66)
      in 1989 and 2.65 (95% CL, 2.39-2.91) in 1997. The thirty-day case fatality rate
      declined dramatically (p < 0.001) from 31% (95% CL, 26-36) to 20% (95% CL, 16-24)
      between 1989 and 1997. Ageing of the population and better identification of
      cases could explain the high incidence rate, whereas the decrease of fatality
      rate may be due to a general improvement in acute care and inclusion of milder
      cases.

PMID- 10938199
TI  - Embryonal tumors in the adult population: implications in therapeutic planning.
AB  - The natural history of neuroectodermal tumors is still debated as far as
      prognostic factors are concerned; the same uncertainty applies to the optimal
      radiotherapy schedule and even more to the presumptive additive effect of
      chemotherapy. The rarity of these tumors and the heterogeneity of management make
      interpretation of literature data also more difficult. We evaluated clinical
      course in a cohort of 39 patients, including 31 with medulloblastoma (MB) and 8
      with primitive neuroectodermal tumors (PNET). All patients were treated with
      radiotherapy, a standardized chemotherapy protocol including PCV scheme, and a
      second-line chemotherapy with cisplatin and etoposide (VP16) at recurrence. In 27
      patients, intrathecal chemotherapy was also delivered. Median follow-up was 10.8
      years. Overall, PNET had a worse outcome as compared to MB: median survival times
      were 42.8 vs. 92.6 months, respectively (p = 0.05). At 5 years, 45% of MB
      patients are alive. No significant difference in disease-free period was found
      between patients of different age, desmoplastic variant, tumor localization, or
      extent of surgery. Patients considered to be "high risk" had a significantly
      shorter disease-free period as compared with low-risk patients (27 vs. 54.7
      months, p = 0.04). Systemic or intrathecal chemotherapy did not influence
      progression-free survival (PFS). However, in the majority of chemotherapy-treated
      patients, a low-dose craniospinal radiotherapy was also delivered. This
      combination of treatments may have avoided the expected increased percentage of
      failure. Moreover, more than half of recurrent patients had a partial response to
      chemotherapy that extended survival for approximately 3 years. Repeated surgery
      and chemotherapy at recurrence favorably influenced survival time.

PMID- 10938198
TI  - Bromocriptine and speech therapy in non-fluent chronic aphasia after stroke.
AB  - The objectives of this study were to investigate the efficacy of bromocriptine
      (BR) combined with speech therapy (ST) to improve a late recovery in non-fluent
      aphasic stroke patients. We performed a double-blind study with high dosage of
      BR, prescribed according to a dose-escalating protocol, comprehensive of clinical
      data, relatives' impression, and language evaluations. The study was divided into
      the following phases: t-0, inclusion; t-30, language re-test to evaluate the
      stability of aphasia; t-90, placebo (PL) and ST; t-150, BR and ST; t-210, BR; t
      270, wash-out. With respect to the baseline assessment, a significant improvement
      was observed in the following tests: dictation (F, 4.8; p < .004), reading
      comprehension (F, 8.1; p < .0003), repetition (F, 3.8; p < .01) and verbal
      latency (F, 4.9; p < .01). High dosage of BR promoted a late recovery in stable
      chronic non-fluent aphasia and this improvement was enhanced by combination with
      ST.

PMID- 10938200
TI  - Chronic inflammatory demyelinating polyradiculoneuropathy: long-term course and
      treatment of 60 patients.
AB  - The objective of this study was to assess the long-term course and treatment of
      chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We evaluated,
      according to a predefined protocol, a series of 60 CIDP patients who received a
      long-term course of steroids and immunosuppressants. Eighteen of them also had
      monoclonal gammopathy of undetermined significance (MGUS). Mean follow-up was 4.4
      years and was similar for CIDP and CIDP-MGUS patients. At the end of the follow
      up, improvement was ascertained in 60% of patients (69% CIDP, 39% CIDP-MGUS).
      Complete remission was achieved in 13%. Out of 26 patients receiving steroids as
      a monotherapy, 19 improved (73%). The following variables were predictive of a
      better outcome: female gender, younger age at onset, relapsing-remitting course,
      and absence of axonal damage at neurophysiologic study. In the multivariate
      analysis, younger age at onset and demyelination without axonal damage still
      retained an independent positive value.

PMID- 10938201
TI  - Primary progressive aphasia: a patient with stress assignment impairment in
      reading aloud.
AB  - Surface dyslexia is a pattern of reading impairment which has been seldom
      described in Italian native speakers. We report the case of a female Italian
      patient, RM, suffering from primary progressive aphasia (PPA) of the fluent type,
      who presented stress assignment errors in reading aloud. In Italian these errors
      are considered to be strongly suggestive of surface dyslexia. We studied RM's
      reading performance in light of existing cognitive models on reading. Since the
      first assessment, she presented multi-level impairment involving pre-semantic,
      lexical-semantic and post-semantic stages. Her stress assignment errors have been
      interpreted as a generalisation of the most frequent tendency in Italian
      language: namely to assign stress to the penultimate syllable. In agreement with
      previous studies, our case suggests that surface dyslexia in PPA is not a
      monolithic entity but, on the contrary, that it may arise from impairment at
      various stages of the reading process.

PMID- 10938202
TI  - A possible association between exposure to n-hexane and parkinsonism.
AB  - Recently, some case-control studies and case reports have shown an association
      between solvent exposure and parkinsonisms. We present a 55-year-old male
      parkinsonian patient with chronic exposure to n-hexane for 17 years. The results
      of neurophysiological (electromyography, evoked potentials), neuroradiological
      (MRI) and neuropsychological tests performed on the patient suggest a role of
      this solvent at the level of the central nervous system. Biological
      susceptibility to neurotoxic compounds is discussed briefly.

PMID- 10938204
TI  - Melkersson-Rosenthal syndrome: report of three cases.
AB  - Melkersson-Rosenthal syndrome is a rare disorder consisting of the triad of
      persistent or recurrent orofacial edema, relapsing facial paralysis and fissured
      tongue. It is far more uncommon to find the complete triad since it generally
      presents in oligosymptomatic forms. We present three cases of the Melkersson
      Rosenthal syndrome with the classic triad of symptoms and discuss the etiology
      and the clinical and electromyography findings of this syndrome.

PMID- 10938203
TI  - Deafness: an unusual onset of genetic Creutzfeldt-Jakob disease.
AB  - We describe a case of genetic Creutzfeldt-Jakob disease (CJD) with deafness at
      the onset. We report clinical features, 14-3-3 protein positivity,
      electroencephalography and brain stem auditory evoked potential abnormalities,
      and high signal on magnetic resonance imaging in basal ganglia and temporal
      cortex. Similarities with CJD Heidenhain variant are discussed.

PMID- 10938205
TI  - Clinical neurophysiology: searching for the cause of some unequivocal symptoms.

PMID- 10938206
TI  - Preoperative treatment with botulinum A toxin in patients with cervical disk
      herniation secondary to dystonic cerebral palsy.

PMID- 10938207
TI  - Fire injuries, disasters, and costs from cigarettes and cigarette lights: a
      global overview.
AB  - BACKGROUND: Fires cause 1% of the global burden of disease. Fire (includes
      explosion) disasters have immense health, social, and environmental costs. We
      will provide initial estimates of overall U. S. and global fire tolls from
      smoking. METHODS: We tabulated and summarized smoking-related fire and disaster
      tolls from published documents. We compared those tolls to U.S. fire, burn, and
      fire death rates per billion cigarettes extrapolated globally. Smoking
      attributable percentages of adult and child access to cigarette lighter and match
      ignitions (lights), and resultant fires, burns, and deaths ignited by young
      children, were estimated from likely smoking-attributable lights usage. Cigarette
      plus cigarette lights fire tolls were multiplied times published and estimated
      fire costs. RESULTS: Smoking is the leading cause of residential or total fire
      death in all eight countries with available statistics. Smoking is a leading
      cause of fires in many more countries. Cigarettes cause numerous fire disasters.
      Cigarette lights cause an estimated 100,000 U.S. and one million global, child
      playing fires per year. Cigarette lights fire injuries likely rival U.S., and
      possibly global, cigarette fire injury numbers. Smoking causes an estimated 30%
      of U. S. and 10% of global fire death burdens. Smoking's estimated U.S. and
      global fire costs were $6.95 (sensitivity range $5.34-22.8) and $27.2
      (sensitivity range $8.2-89.2) billion, respectively, in 1998 U. S. dollars.
      CONCLUSIONS: Smoking likely causes large global fire tolls. U.S. fire tolls have
      fallen when smoking decreased. Further reducing smoking can substantially reduce
      fire and disaster tolls.

PMID- 10938208
TI  - A message from preventive medicine and your physician. Prostate cancer.

PMID- 10938209
TI  - Middle-aged men--a risk category regarding fatal poisoning due to
      dextropropoxyphene and alcohol in combination.
AB  - BACKGROUND: Dextropropoxyphene (DXP) toxicity is highly potentiated by alcohol
      and the aim of this study was to determine the characteristics of non-suicidal
      deceased with simultaneous occurrence of alcohol and DXP in the blood. METHODS:
      The investigated population was based on the total medico-legal autopsy material
      in Sweden during the years 1992-1996. Toxicological analyses and death
      certificates were examined. RESULTS: Simultaneous occurrence of DXP and alcohol
      was detected in 425 cases. The mean blood alcohol concentration was 0.14%. One
      third had a blood alcohol concentration >;0.20% and 42%, <0.1%. The majority of
      the cases were found between the ages 30 and 59 years;, 71% were male and 29%
      were female. Notes on alcoholism were found in 16% of the cases. CONCLUSION:
      Middle-aged, habitual or social-drinking men, on medication for pain, are most
      prone to combine DXP and alcohol and are most vulnerable to be victims of
      accidental poisoning due to the combination of DXP and alcohol. We propose strict
      regulations in prescription, or even a ban on prescription of DXP, and that
      physicians in the meantime pay extra attention to this risk category of patients
      and make sure that the patient is well informed of the life-threatening risks of
      simultaneous use of DXP and alcohol.

PMID- 10938210
TI  - A model of smoking among inner-city adolescents: the role of personal competence
      and perceived social benefits of smoking.
AB  - BACKGROUND: Based on current trends, smoking will remain a major public health
      problem in the 21st century. Effective smoking prevention approaches offer the
      best hope for decreasing the rise in adolescent smoking rates. Competence
      enhancement approaches to smoking prevention are among the most successful. Yet,
      there is not a full understanding of how effective prevention approaches work.
      This study tests whether a deficiency in competence (poor decision-making skills
      and low personal efficacy) is linked to acquiring beliefs in the perceived
      benefits of smoking and whether these perceived benefits are then related to
      subsequent smoking. METHODS: A sample of 1459 students attending 22 middle and
      junior high schools in New York City participated. Students completed surveys at
      baseline, 1-year follow-up and 2-year follow-up during a regular class period.
      They self-reported smoking, decision-making skills, personal efficacy and beliefs
      in the perceived benefits of smoking. RESULTS: The tested structural equation
      model had a good fit and was parsimonious and consistent with the theory
      underlying the competence approach to smoking prevention. CONCLUSIONS: This
      research highlights the importance of addressing decision-making skills, personal
      efficacy, and beliefs in the social benefits of smoking within adolescent smoking
      prevention programs.

PMID- 10938211
TI  - Predictors of cigarette and alcohol susceptibility and use among Hispanic migrant
      adolescents.
AB  - BACKGROUND: Little is known about interpersonal and broader sociocultural factors
      related to protection from or use of tobacco and alcohol among immigrant
      adolescents. This study presents the baseline predictors of tobacco and alcohol
      use and susceptibility to tobacco and alcohol among Hispanic migrant adolescents.
      METHODS: The sample consisted of 660 Hispanic adolescents (51% male) between the
      ages of 11 and 16 years enrolled in the Migrant Education Program through the
      County Office of Education. Slightly more than 75% of the study sample was first
      generation Hispanics and 79% preferred to speak Spanish. An interviewer
      administered survey assessed the following information: standard demographic
      characteristics, modeling of cigarette smoking (including parental and peer
      smoking), attitudes (including self-standards and anticipated outcomes),
      acculturation, communication with parents, amount of social support, and
      satisfaction with social support. RESULTS: Significant predictors of
      susceptibility to tobacco and smoking status included age, gender, attitudes
      toward cigarettes (e.g., anticipated outcomes, self-standards), satisfaction with
      social support, and parent-child communication. Factors that were also
      significant predictors of susceptibility to alcohol and drinking status were age,
      attitudes toward drinking, satisfaction with social support, and level of parent
      child communication. In addition, peer and household use of alcohol predicted
      adolescent outcomes. CONCLUSIONS: Based on these results it is suggested that
      tobacco and alcohol prevention efforts for first-generation Hispanic adolescents
      should target not only usual concerns (e.g., availability, peer pressure,
      modeling, expectancies), but also parent-child communication.

PMID- 10938212
TI  - Evaluation of a tobacco and alcohol use prevention program for Hispanic migrant
      adolescents: promoting the protective factor of parent-child communication.
AB  - BACKGROUND: Interventions designed to prevent tobacco and alcohol use targeting
      high-risk adolescents are limited. In addition, few studies have attempted to
      improve parent-child communication skills as a way of improving and maintaining
      healthy youth decision-making. METHODS: A total of 660 Hispanic migrant families
      participated in a randomized pre-post control group study that was utilized to
      determine the impact of the intervention on parent-child communication. Both
      treatment and attention-control groups of youth were exposed to an eight-session
      culturally sensitive program presented by bilingual/bicultural college students.
      Parents jointly attended three of the eight sessions and participated in helping
      their child complete homework assignments supporting the content of each session.
      The content of the treatment intervention included (1) information about tobacco
      and alcohol effects, (2) social skills training (i.e., refusal skills), and (3)
      the specific development of parent-child communication skills to support healthy
      youth decisions. RESULTS: Significant intervention by household size interactions
      for both parent and youth perceptions of communication were found indicating that
      the treatment was effective in increasing communication in families with fewer
      children. Based on the effect size and the previously established relationship
      between communication and susceptibility to tobacco and alcohol use, it was
      determined that the intervention effect could be translated into a future 5 to
      10% decrease in susceptibility for these smaller families. CONCLUSIONS: A
      culturally sensitive family-based intervention for migrant Hispanic youth was
      found to be effective in increasing perceived parent-child communication in
      families with fewer children. It is expected that increases in this important
      protective factor will lead to later observed decreases in tobacco and alcohol
      use.

PMID- 10938213
TI  - Predictors of the use of sunscreen in dermatological patients in Central Europe.
AB  - BACKGROUND: There is mounting evidence that sun exposure is a cause of skin
      cancer. Therefore, the focus of skin cancer prevention is on sun protection. The
      present study investigated the use of sunscreens in a sample from the adult
      Central European population. METHODS: As part of a case-control study of
      cutaneous melanoma, a total of 498 controls with classical dermatological
      disorders were selected from hospitals in Central Europe. All people underwent
      whole-body skin examinations and were interviewed using a standardized
      questionnaire. RESULTS: Overall, 40.8% of the people never used sunscreen and of
      the 281 persons who used sunscreen, 41.5% applied it only once per sun bath.
      Persons who did not use sunscreen tended to be older (P<0.0001) and of male
      gender (P = 0.0004). Young people, women, and people who expressed a positive
      attitude to the sun spent more time in the sun and were more likely to apply
      sunscreens. People who worked almost always outdoors had a six times increased
      odds ratio of not using sunscreens (P<0.0001) compared to people who worked
      always indoors. CONCLUSIONS: Men, older people, and outdoor workers should be
      targeted in health education campaigns. On the other hand, people who apply
      sunscreen as a means of sun protection should be advised about adequate usage.

PMID- 10938215
TI  - Effects of the transdermal nicotine patch on normalization of HDL-C and its
      subfractions.
AB  - BACKGROUND: Smoking reduces HDL-C and its subfractions, and smoking cessation
      leads to normalization of these lipoproteins. Nicotine replacement therapy is an
      important weapon employed by those attempting to quit smoking. This study
      examined the effects of the transdermal nicotine patch ("patch") on lipoproteins.
      METHODS: Ten male and 17 female smokers refrained from smoking for 77 days. The
      patch was utilized during the first 35 days and then removed for the remaining 42
      days. Seven male and 9 female nonsmokers were controls. RESULTS: HDL-C, HDL(2)-C,
      and HDL(3)-C levels were significantly lower in smokers when compared with
      controls. These differences were sustained during the initial 35 days when using
      the patch. Over the following 42 days, however, these lipoproteins normalized to
      values similar to those of control subjects. Females who quit smoking gained 2.1
      kg after the patch was removed. CONCLUSIONS: It was concluded that nicotine as
      administered by the transdermal nicotine patch inhibits normalization of HDL-C,
      HDL(2)-C, and HDL(3)-C in those who have quit smoking. Removal of the patch
      results in normalization of these lipoproteins. The patch appeared to prevent
      weight gain among female subjects.

PMID- 10938214
TI  - Prevalence and co-occurrence of health risk behaviors among high-risk drinkers in
      a primary care population.
AB  - BACKGROUND: Approximately 10% of patients seen in the primary care setting meet
      criteria for high-risk (HR) drinking. Little data are available about the co
      occurrence of other risk behaviors (RBs) in this population. This study examines
      the co-occurrence of smoking, poor diet, and sedentariness, and several change
      related variables, among 479 HR drinkers participating in Project Health, a NIAAA
      funded study testing the effectiveness of a provider-delivered intervention to
      reduce HR drinking. METHOD: Data were collected at study entry via standardized
      interview and questionnaire. RESULTS: The prevalence of additional RBs among HR
      drinkers was smoking, 35%; poor diet, 28%; and sedentariness, 44%. In addition to
      HR drinking, 67% of participants had at least one RB, and 61% reported smoking,
      sedentariness, or both. Perception of drinking as a problem was generally low
      (20%), as was intention to change drinking. Seventy-two percent of participants
      with multiple RBs perceived at least one of these RBs as a problem. Younger,
      unmarried, less-educated, blue-collar, and non-working participants were more
      likely to have multiple RBs than white-collar workers. CONCLUSION: Additional RBs
      are common among HR drinkers and may increase their already elevated health
      risks. Implications of these findings for interventions integrating multiple RBs
      into primary care settings are discussed.

PMID- 10938216
TI  - Inconsistencies in the classification of preventive interventions.
AB  - BACKGROUND AND OBJECTIVE: Preventive measures are commonly classified into
      primary (prevention of a disease from occurring), secondary (screening of
      asymptomatic persons with a view of early detection and treatment of disease),
      and tertiary (treatment of patients with a view of palliation, cure,
      rehabilitation, prevention of relapse, or prevention of complications). The
      objective of the present survey was to assess the adherence to this
      classification in a sample of abstracts of scientific publications. METHOD: We
      searched the literature (key terms prevention and primary, secondary, or
      tertiary) and identified 317 abstracts describing various preventive
      interventions. We tabulated the level of prevention as defined in the abstract,
      by what was done, to whom, and why. MAIN FINDINGS: There was a considerable
      variability in the way the various levels of prevention were defined in the
      reviewed abstracts. CONCLUSIONS: The definitions of the levels of prevention are
      not specific enough to be appropriately used by all. We suggest, therefore, to
      define clinical interventions by their objective, target population, and type
      ("reduction of mortality of patients with symptomatic ventricular ectopy by beta
      blockers"), rather than in terms of level of prevention ("tertiary prevention of
      ventricular ectopy").

PMID- 10938217
TI  - Smoking by patients in a smoke-free hospital: prevalence, predictors, and
      implications.
AB  - BACKGROUND: No-smoking policies are now mandated in all U.S. hospitals. They
      require hospitalized smokers to abstain temporarily from tobacco. Little is known
      about patients' compliance with these policies or about their effects on
      patients' comfort and subsequent smoking behavior. Hospitalization in a smoke
      free hospital might precipitate nicotine withdrawal in smokers, but it might also
      offer smokers an opportunity to stop smoking. METHODS: To assess the prevalence,
      predictors, and implications of smoking during hospitalization, we analyzed data
      from a cohort of 650 adult smokers who were admitted to an urban teaching
      hospital and participating in a smoking intervention trial. We measured nicotine
      withdrawal symptoms at study entry (24-48 h after admission) and patients' self
      reports of smoking while hospitalized, compliance with the hospital no-smoking
      policy (smoking prohibited indoors but permitted outdoors), and smoking status 1
      and 6 months after discharge. RESULTS: One-quarter of smokers admitted to a smoke
      free hospital reported smoking during their hospital stay, although only 4% of
      smokers admitted violating policy by smoking indoors. Within 48 h of admission,
      55% of smokers reported cigarette cravings and 29% of smokers reported difficulty
      refraining from smoking. Smokers with cigarette cravings were more likely to
      smoke while hospitalized (OR 3.6; 95% CI: 1.9-6.7). Those with nicotine
      withdrawal symptoms were more likely to violate the hospital no-smoking policy
      (OR 6.8; 95% CI: 5.3-8.3). Abstaining from tobacco use while hospitalized was a
      strong independent predictor of continued abstinence after discharge (OR 3.8; 95%
      CI: 1.4-10.3). CONCLUSIONS: Smoking by patients in a smoke-free hospital was
      common. Craving for cigarettes and symptoms consistent with nicotine withdrawal
      occurred frequently in hospitalized smokers and were associated with smoking
      during hospitalization, which was itself strongly linked with continuing to smoke
      after discharge. Pharmacologic treatment of cigarette cravings in hospitalized
      smokers could potentially improve patient comfort, increase compliance with
      hospital no-smoking policies, and promote smoking cessation after hospital
      discharge. This approach deserves further study.

PMID- 10938218
TI  - Direct observation of rates of preventive service delivery in community family
      practice.
AB  - BACKGROUND: Data on preventive service delivery in primary care practice have
      been limited by indirect methods of measurement. This study describes directly
      observed rates of preventive service delivery during outpatient visits to
      community family physicians. METHODS: In a multimethod cross-sectional study,
      research nurses directly observed consecutive patient visits in the offices of
      138 family physicians in Northeast Ohio. Patient eligibility for services
      recommended by the U.S. Preventive Services Task Force was determined from
      medical record review. Service delivery was assessed by direct observation of
      outpatient visits. Rates of delivery of specific preventive services were
      computed. Global summary measures were calculated for health habit counseling,
      screening, and immunization services. RESULTS: Among 4,049 visits by established
      patients with available medical records, wide variation was observed among rates
      of different preventive services delivered during well-care visits. During
      illness visits, rates were uniformly low for all preventive services. Counseling
      services were delivered at only slightly lower rates during illness visits
      compared to well visits. Patients were up to date on 55% of screening, 24% of
      immunization, and 9% of health habit counseling services. CONCLUSION: Rates of
      preventive service delivery are low. Illness visits are important opportunities
      to deliver preventive services, particularly health habit counseling, to
      patients. Preventive service delivery summary scores are useful in providing a
      patient population perspective on the delivery of preventive services and in
      focusing attention on delivery of a comprehensive portfolio of services.

PMID- 10938219
TI  - Health behaviors of smokers, ex-smokers, and never smokers in an HMO.
AB  - BACKGROUND: The preponderance of evidence suggests that smokers do not engage in
      health-promoting lifestyles compared to nonsmokers. Few studies, however, have
      considered possible differences in health behaviors among smokers at different
      stages of intention to change. In this paper we examined the relationship of
      smoking stage of change to health behaviors in an HMO population. METHODS: Data
      were obtained from a baseline health status and preventive service evaluation
      survey mailed to 8000 HMO members over the age of 40. The sample was stratified
      based on the presence of one or more chronic diseases. Regression analyses were
      performed adjusting for covariates and weighting based on the stratification.
      RESULTS: Smokers appear to vary by stage of change in their practice of health
      promoting behaviors. After controlling for age, gender, professional advice,
      chronic disease, and education, smokers classified in early stages of change
      demonstrated significantly fewer positive health practices compared to never
      smokers. A consistent pattern emerged across health behaviors. CONCLUSIONS:
      Smokers in the earliest stages of change appear to have the most room for
      improvement compared to ex-smokers and never smokers. Behavior change other than
      smoking could be an opportunity to engage early stage smokers.

PMID- 10938221
TI  - Curt Richter and regulatory physiology.
AB  - Curt Richter made seminal contributions to our understanding of a number of
      issues regarding the relationships between physiology and behavior. He was the
      first to conceptualize behavior as an aspect of regulatory physiology. These
      ideas developed from his work on behavioral responses to a variety of
      physiological perturbations. The classic example is Richter's demonstration of
      the development of avid sodium ingestion in response to urinary sodium loss after
      adrenalectomy. Some of Richter's ideas on the nature and underlying physiology of
      specific appetites maintain their influence and continue to stimulate active
      investigation. Others, focused on abilities to self-select balanced diets, have
      not borne the test of time or experimental challenge. As current research takes a
      more molecular focus, Richter's ideas on behavior in the service of the internal
      milieu maintain their currency, and the search for the molecular bases for these
      relationships should serve as a research focus.

PMID- 10938220
TI  - Psychosocial predictors of changes in physical activity in overweight sedentary
      adults following counseling in primary care.
AB  - BACKGROUND: Increasing regular physical activity in adults at elevated risk of
      cardiovascular disease is an important target for preventive medicine. This study
      evaluated demographic, social and cognitive predictors of self-reported changes
      in physical activity after 4 and 12 months in a randomized trial of behavioral
      counseling in primary care. METHOD: Data were analyzed from 234 male and 271
      female sedentary patients with a body mass index of 25-35 (age 49.1 years, SD
      11.2 years), who had been counseled by nurses in general practice using stage
      matched behavioral methods or standard health promotion and who were reassessed
      after 4 months. A total of 187 men and 231 women were reassessed after 12 months.
      RESULTS: Physical activity at baseline was associated with educational status,
      having a partner who exercised, perceived barriers, and self-efficacy. Changes
      over 4 months were greater with behavioral counseling, in non-smokers and in
      patients with higher ratings of motivation to change and self-efficacy at
      baseline. Changes over 12 months were greater with behavioral counseling and were
      predicted in the behavioral group by social support variables, perceived
      benefits, and barriers. Stage of readiness to change predicted increased activity
      at 4 but not 12 months. CONCLUSIONS: Social support and cognitive variables
      predict increased physical activity following counseling in primary care of
      sedentary overweight adults. Different factors are relevant to short- and long
      term modifications in behavior.

PMID- 10938223
TI  - Thermal compensation of peripheral oxygen transport in skeletal muscle of
      seasonally acclimatized trout.
AB  - Seasonal changes in ultrastructure of locomotory muscle were quantified after
      acclimatization to natural temperature and photoperiod. Only modest changes were
      seen in the volume density (V(v)) of mitochondria in slow fibers ranging from
      0.21 +/- 0.01 (summer) to 0.24 +/- 0.01 (winter), despite an increase in fiber
      size from 945 +/- 19 to 1,594 +/- 46 microm(2), respectively, resulting in a
      significantly greater total mitochondrial volume at low temperatures. In
      contrast, intracellular lipid stores showed a marked change with season, from a
      maximum V(v) of lipid droplets of 0.16 +/- 0.01 in winter, progressively
      declining through spring and summer to a minimum of 0.07 +/- 0.01 in autumn. For
      both organelles, the surface density reflected changes in V(v), indicating little
      modification of structure. Seasonal effects may dominate those of environmental
      temperature on mitochondrial separation, which in winter and spring fish at 4(o)C
      averaged 0.64 +/- 0.06 and 1.20 +/- 0.07 microm, respectively. The extracellular
      transport of oxygen also varies with season, the peak capillary density in autumn
      (2,851 +/- 88 mm(-2)) resulting in a minimum tissue supply (domain) area of 529
      +/- 9 microm(2) per capillary. As a consequence, the predicted intracellular
      PO(2) ( approximately 2.5 kPa) is similar throughout the year.

PMID- 10938222
TI  - Sympathoexcitatory CVLM neurons mediate responses to caudal pressor area
      stimulation.
AB  - Neurons in the caudal pressor area (CPA) are a source of tonic sympathoexcitation
      that is dependent on activation of cardiovascular sympathetic premotor neurons in
      the rostral ventrolateral medulla (RVLM). In the present study, we sought to
      clarify the mechanism through which CPA neurons elicit increases in RVLM neuronal
      discharge, vasoconstrictor sympathetic tone, and arterial pressure. In urethan
      chloralose-anesthetized, paralyzed, and artificially ventilated rats, bilateral
      disinhibition of CPA with bicuculline (Bic) after bilateral disinhibition of
      caudal ventrolateral medulla (CVLM) caused increases in splanchnic sympathetic
      nerve activity (+277% control) and arterial pressure (+54 mmHg). Inhibition of
      CVLM neurons with muscimol abolished the pressor response to activation of CPA
      neurons, suggesting that neurons within CVLM mediate the excitatory responses
      from CPA. Disinhibition of CVLM and CPA with Bic enhanced the sympathoexcitatory
      responses to stimulation of CPA with DL-homocysteic acid, which were blocked by
      microinjections of kynurenic acid into CVLM. We conclude that the pathway from
      CPA to RVLM involves an obligatory glutamatergic activation of sympathoexcitatory
      neurons in the vicinity of CVLM.

PMID- 10938224
TI  - Effect of 17beta-estradiol on the expression of somatostatin genes in rainbow
      trout (Oncorhynchus mykiss).
AB  - In the present study, the effects of 17beta-estradiol (E(2)) treatment on the
      expression of preprosomatostatin (PPSS) I, PPSS II', and PPSS II" mRNA in the
      hypothalamus and endocrine pancreas (Brockmann body), as well as the effects of
      E(2) treatment on plasma somatostatin (SS)-14 and -25 concentrations in sexually
      immature rainbow trout (Oncorhynchus mykiss), were investigated. E(2) treatment
      significantly (P < 0.001) depressed both plasma SS-14 and SS-25. In the
      hypothalamus, E(2) treatment significantly (P < 0.001) decreased the levels of
      PPSS I and PPSS II" mRNA. However, there was no effect of E(2) treatment on PPSS
      II' mRNA levels. In the pancreas, E(2) treatment had no significant effect on the
      levels of either PPSS II' mRNA or PPSS II" mRNA. However, E(2) treatment
      significantly (P < 0.005) decreased levels of PPSS I mRNA. These data suggest
      that E(2) acts, in part, to increase plasma growth hormone levels in rainbow
      trout by decreasing the endogenous inhibitory somatostatinergic tone by
      inhibiting plasma levels of both SS-14 and SS-25 and hypothalamic levels of mRNA
      encoding these proteins.

PMID- 10938225
TI  - Fictive locomotion and scratching inhibit dorsal horn neurons receiving thin
      fiber afferent input.
AB  - In decerebrate paralyzed cats, we examined the effects of two central motor
      commands (fictive locomotion and scratching) on the discharge of dorsal horn
      neurons receiving input from group III and IV tibial nerve afferents. We recorded
      the impulse activity of 74 dorsal horn neurons, each of which received group III
      input from the tibial nerve. Electrical stimulation of the mesencephalic
      locomotor region (MLR), which evoked fictive static contraction or fictive
      locomotion, inhibited the discharge of 44 of the 64 dorsal horn neurons tested.
      The mean depth from the dorsal surface of the spinal cord of the 44 neurons whose
      discharge was inhibited by MLR stimulation was 1.77 +/- 0.04 mm. Fictive
      scratching, evoked by topical application of bicuculline to the cervical spinal
      cord and irritation of the ear, inhibited the discharge of 22 of the 29 dorsal
      horn neurons tested. Fourteen of the twenty-two neurons whose discharge was
      inhibited by fictive scratching were found to be inhibited by MLR stimulation as
      well. The mean depth from the dorsal surface of the cord of the 22 neurons whose
      discharge was inhibited by fictive scratching was 1.77 +/- 0.06 mm. Stimulation
      of the MLR or the elicitation of fictive scratching had no effect on the activity
      of 22 dorsal horn neurons receiving input from group III and IV tibial nerve
      afferents. The mean depth from the dorsal surface of the cord was 1.17 +/- 0.07
      mm, a value that was significantly (P < 0.05) less than that for the neurons
      whose discharge was inhibited by either MLR stimulation or fictive scratching. We
      conclude that centrally evoked motor commands can inhibit the discharge of dorsal
      horn neurons receiving thin fiber input from the periphery.

PMID- 10938226
TI  - Nuclear factor-kappaB inhibitor peptide inhibits spontaneous and interleukin
      1beta-induced sleep.
AB  - Nuclear factor-kappaB (NF-kappaB) is a transcription factor that when activated
      promotes production of several sleep-promoting substances such as interleukin
      1beta (IL-1beta), tumor necrosis factor-alpha, and nerve growth factor.
      Therefore, we hypothesized that inhibition of NF-kappaB activation would
      attenuate sleep. A NF-kappaB cell-permeable inhibitor peptide (IP) was injected
      intracerebroventricularly (5 and 50 microg for rats, 100 microg for rabbits). On
      a separate day, time-matched control injections of a cell-permeable inactive
      control peptide were done in the same animals. The 50-microg dose of IP in rats
      and the 100-microg dose in rabbits significantly inhibited non-rapid eye movement
      sleep and rapid eye movement sleep if administered during the light period.
      Moreover, pretreatment of rabbits with 100 microg of the IP 12 h before
      intracerebroventricular injection of IL-1beta (10 ng) significantly attenuated IL
      1beta-induced sleep and febrile responses. The current data support the
      hypothesis that a brain cytokine network is involved in sleep regulation and that
      NF-kappaB is a crucial factor in physiological sleep regulation.

PMID- 10938227
TI  - Intracellular pH regulation in neurons from chemosensitive and nonchemosensitive
      regions of Helix aspersa.
AB  - We used 2',7'-bis(carboxyethyl)-5(6)-carboxyflourescein (BCECF), a pH-sensitive
      fluorescent dye, to study intracellular pH (pH(i)) regulation in neurons in CO(2)
      chemoreceptor and nonchemoreceptor regions in the pulmonate, terrestrial snail,
      Helix aspersa. We studied pH(i) during hypercapnic acidosis, after ammonia
      prepulse, and during isohydric hypercapnia. In all treatment conditions, pH(i)
      fell to similar levels in chemoreceptor and nonchemoreceptor regions. However,
      pH(i) recovery was consistently slower in chemoreceptor regions compared with
      nonchemoreceptor regions, and pH(i) recovery was slower in all regions when
      extracellular pH (pH(e)) was also reduced. We also studied the effect of
      amiloride and DIDS on pH(i) regulation during isohydric hypercapnia. An amiloride
      sensitive mechanism was the dominant pH(i) regulatory process during acidosis. We
      conclude that pH(e) modulates and slows pH(i) regulation in chemoreceptor regions
      to a greater extent than in nonchemoreceptor regions by inhibiting an amiloride
      sensitive Na(+)/H(+) exchanger. Although the phylogenetic distance between
      vertebrates and invertebrates is large, similar results have been reported in
      CO(2)-sensitive regions within the rat brain stem.

PMID- 10938228
TI  - PACAP contributes to insulin secretion after gastric glucose gavage in mice.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is localized to
      pancreatic ganglia governing the parasympathetic nerves, which contribute to
      prandial insulin secretion. We hypothesized that this contribution involves PACAP
      and show here that the PACAP receptor antagonist PACAP-(6---27) (1.5 nmol/kg iv)
      reduces the 15-min insulin response to gastric glucose (150 mg/mouse) by 18% in
      anesthetized mice (P = 0.041). The reduced insulinemia was not due to inhibited
      release of the incretin factor glucagon-like peptide 1 (GLP-1) because PACAP-(6--
      27) enhanced the GLP-1 response to gastric glucose. Furthermore, the GLP-1
      antagonist exendin-3-(9---39) (30 nmol/kg) exerted additive inhibitory effect on
      the insulin response when combined with PACAP-(6---27). The PACAP antagonism was
      specific because intravenous PACAP-(6---27) inhibited the insulin response to
      intravenous PACAP-27 plus glucose without affecting the insulin response to
      intravenous glucose alone (1 g/kg) or glucose together with other insulin
      secretagogues of potential incretin relevance of intestinal (GLP-1, gastric
      inhibitory polypeptide, cholecystokinin) and neural (vasoactive intestinal
      peptide, gastrin-releasing peptide, cholinergic agonism) origin. We conclude that
      PACAP contributes to the insulin response to gastric glucose in mice and suggest
      that PACAP is involved in the regulation of prandial insulin secretion.

PMID- 10938229
TI  - Chemotransduction properties of nodose ganglion cardiac afferent neurons in
      guinea pigs.
AB  - To determine the chemotransduction characteristics of ventricular sensory
      neurites associated with nodose ganglion afferent neurons, various chemicals were
      applied individually to epicardial sensory neurites associated with individual
      afferent neurons in anesthetized guinea pigs. The following ion channel-modifying
      agents were tested: barium chloride, cadmium chloride, calcium chloride, the
      chelating agent EGTA, nickel chloride, potassium chloride, tetraethylammonium
      chloride, and veratridine. An acidic solution (pH 6.0) and oxygen-derived free
      radicals (H(2)O(2)) were tested. The following chemicals were also tested:
      adenosine, alpha- and beta-adrenergic agonists, angiotensin II, bradykinin,
      calcitonin gene-related peptide (CGRP), histamine, nicotine, the nitric oxide
      donor nitroprusside, substance P, and vasoactive intestinal peptide. A total of
      102 cardiac afferent neurons was identified, of which approximately 66% were
      sensitive to mechanical stimuli applied to their epicardial sensory fields.
      Application of individual ion channel-modifying agents to epicardial sensory
      fields modified most associated afferent neurons, with barium chloride affecting
      each neuron studied. Ventricular sensory neurites associated with most identified
      neurons were also responsive to the other tested chemicals, with hydrogen
      peroxide, adenosine, angiotensin II, bradykinin, CGRP, clonidine, and nicotine
      inducing responses from at least 75% of the neurons studied. It is concluded that
      1) the ventricular sensory neurites associated with nodose ganglion afferent
      neurons transduce a much wider variety of chemical stimuli than considered
      previously, 2) these sensory neurites employ a variety of membrane ion channels
      in their transduction processes in situ, and 3) adrenergic agents influence on
      sensory neurites associated with cardiac afferent neurons suggests the presence
      of a cardiac feedback mechanism involving local catecholamine release by adjacent
      sympathetic efferent postganglionic nerve terminals.

PMID- 10938230
TI  - Head-down bed rest alters sympathetic and cardiovascular responses to mental
      stress.
AB  - Astronauts usually work under much mental stress. However, it is unclear how and
      whether or not an exposure to microgravity affects physiological response to
      mental stress in humans. To examine effects of microgravity on vasomotor
      sympathetic and peripheral vasodilator responses to mental stress, we performed
      10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down
      bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle
      sympathetic nerve activity (MSNA, measured by microneurography) slightly
      increased during MA before HDBR, and this increase was augmented after HDBR. Calf
      blood flow (measured by venous occlusion plethysmography) increased and calf
      vascular resistance (calculated by dividing mean blood pressure by calf blood
      flow) decreased during MA before HDBR, but these responses were abolished after
      HDBR. Increases in heart rate and mean blood pressure during MA were not
      different between before and after HDBR. These findings suggest that HDBR
      augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf
      muscle in response to mental stress.

PMID- 10938231
TI  - Role of potassium channels in catecholamine secretion in the rat adrenal gland.
AB  - We elucidated the functional contribution of K(+) channels to cholinergic control
      of catecholamine secretion in the perfused rat adrenal gland. The small
      conductance Ca(2+)-activated K(+) (SK(Ca))-channel blocker apamin (10-100 nM)
      enhanced the transmural electrical stimulation (ES; 1-10 Hz)- and 1, 1-dimethyl-4
      phenyl-piperazinium (DMPP; 5-40 microM)-induced increases in norepinephrine (NE)
      output, whereas it did not affect the epinephrine (Epi) responses. Apamin
      enhanced the catecholamine responses induced by acetylcholine (6-200 microM) and
      methacholine (10-300 microM). The putative large-conductance Ca(2+)-activated
      K(+) channel blocker charybdotoxin (10-100 nM) enhanced the catecholamine
      responses induced by ES, but not the responses induced by cholinergic agonists.
      Neither the K(A) channel blocker mast cell degranulating peptide (100-1000 nM)
      nor the K(V) channel blocker margatoxin (10-100 nM) affected the catecholamine
      responses. These results suggest that SK(Ca) channels play an inhibitory role in
      adrenal catecholamine secretion mediated by muscarinic receptors and also in the
      nicotinic receptor-mediated secretion of NE, but not of Epi. Charybdotoxin
      sensitive Ca(2+)-activated K(+) channels may control the secretion at the
      presynaptic site.

PMID- 10938232
TI  - Role of cytochrome P-450 in endogenous antipyresis.
AB  - In previous reports, we (15, 18) and others (29) demonstrated data showing that
      various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and
      mice, indicating that the enzyme may be involved in endogenous antipyresis. The
      aim of this study was to further test the hypothesis that the P-450-dependent
      epoxygenase pathway of arachidonic acid is part of the homeostatic system to
      control the height of fever. Sprague-Dawley rats were implanted with
      biotelemeters to monitor body temperature. Fever was induced by intraperitoneal
      injection of lipopolysaccharide (LPS; 80 microg/kg). We demonstrate that
      intraperitoneal administration of P-450 inducers (bezafibrate and
      dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a
      dose-dependent manner. In complementary experiments, rats were implanted with
      brain cannulas in addition to the biotelemeters. Various isomers of
      epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to
      10 microg/rat to test their influence on LPS-induced fever in rats. Four of five
      isomers were antipyretic in a dose-dependent manner. The most potent antipyretic
      isomers were 11, 12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9
      EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis
      that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part
      of the endogenous antipyretic system.

PMID- 10938233
TI  - Accumulation of quercetin conjugates in blood plasma after the short-term
      ingestion of onion by women.
AB  - Quercetin is a typical flavonoid present mostly as glycosides in plant foods; it
      has attracted much attention for its potential beneficial effects in disease
      prevention. In this study, we examined human volunteers after the short-term
      ingestion of onion, a vegetable rich in quercetin glucosides. The subjects were
      served diets containing onion slices (quercetin equivalent: 67.6-93.6 mg/day)
      with meals for 1 wk. Quercetin was only found in glucuronidase-sulfatase-treated
      plasma, and its concentration after 10 h of fasting increased from 0.04 +/- 0.04
      microM before the trial to 0.63 +/- 0.72 microM after the 1-wk trial. The
      quercetin content in low-density lipoprotein (LDL) after glucuronidase-sulfatase
      treatment corresponded to <1% of the alpha-tocopherol content. Human LDL isolated
      from the plasma after the trial showed little improvement of its resistance to
      copper ion-induced oxidation. It is therefore concluded that conjugated
      metabolites of quercetin accumulate exclusively in human blood plasma in the
      concentration range of 10(-7) approximately 10(-6) M after the short-term
      ingestion of vegetables rich in quercetin glucosides, although these metabolites
      are hardly incorporated into plasma LDL.

PMID- 10938234
TI  - Exogenous and endogenous corticosteroids modulate blood-brain barrier development
      in the ovine fetus.
AB  - We previously reported decreases in blood-brain barrier permeability in the ovine
      fetus at 80% of gestation after antenatal corticosteroids and shown that
      permeability is not reduced in newborn lambs after postnatal corticosteroids. We
      now test the hypotheses that exogenous antenatal corticosteroids decrease blood
      brain barrier permeability at 60% but not 90% of gestation in ovine fetuses and
      that endogenous increases in plasma cortisol concentrations are associated with
      ontogenic decreases in barrier permeability during gestation. Chronically
      instrumented ovine fetuses were studied 12 h after the last of four 6-mg
      dexamethasone or placebo injections were given 12 h apart over 48 h to ewes.
      Fetuses at 80% of gestation from placebo-treated ewes studied under the same
      protocol were also included. Blood-brain barrier function was quantified with the
      blood-to-brain transfer constant (K(i)) to alpha-aminoisobutyric acid. K(i)
      values were lower in cerebral cortex, caudate nucleus, hippocampus, superior
      colliculus, thalamus, medulla, and cervical spinal cord in fetuses of
      dexamethasone- than placebo-treated ewes at 60% but not 90% of gestation.
      Regional brain K(i) values demonstrated inverse correlations with increases in
      gestation and plasma cortisol concentrations in most brain regions. We conclude
      that maternal treatment with exogenous corticosteroids was associated with
      decreases in blood-brain barrier permeability at 60% but not 90% of gestation and
      that increases in gestation and endogenous cortisol concentrations were
      associated with ontogenic decreases in barrier permeability during fetal
      development.

PMID- 10938235
TI  - Limb congestion enhances the synchronization of sympathetic outflow with muscle
      contraction.
AB  - In this report, we examined if the synchronization of muscle sympathetic nerve
      activity (MSNA) with muscle contraction is enhanced by limb congestion. To
      explore this relationship, we applied signal-averaging techniques to the MSNA
      signal obtained during short bouts of forearm contraction (2-s contraction/3-s
      rest cycle) at 40% maximal voluntary contraction for 5 min. We performed this
      analysis before and after forearm venous congestion; an intervention that
      augments the autonomic response to sustained static muscle contractions via a
      local effect on muscle afferents. There was an increased percentage of the MSNA
      noted during second 2 of the 5-s contraction/rest cycles. The percentage of total
      MSNA seen during this particular second increased from minute 1 to 5 of
      contraction and was increased further by limb congestion (control minute 1 = 25.6
      +/- 2.0%, minute 5 = 32.8 +/- 2.2%; limb congestion minute 1 = 29.3 +/- 2.1%,
      minute 5 = 37.8 +/- 3.9%; exercise main effect <0.005; limb congestion main
      effect P = 0.054). These changes in the distribution of signal-averaged MSNA were
      seen despite the fact that the mean number of sympathetic discharges did not
      increase over baseline. We conclude that synchronization of contraction and MSNA
      is seen during short repetitive bouts of handgrip. The sensitizing effect of
      contraction time and limb congestion are apparently due to feedback from muscle
      afferents within the exercising muscle.

PMID- 10938236
TI  - Cardiovascular actions of centrally and peripherally administered trout urotensin
      I in the trout.
AB  - The cardiovascular effects of centrally and peripherally administered synthetic
      trout urotensin (U)-I, a member of the corticotropin-releasing hormone family of
      neuroendocrine peptides, were investigated in unanesthetized rainbow trout
      Oncorhynchus mykiss. Intracerebroventricular injections of U-I (5.0 and 12.5
      pmol) produced a sustained increase in mean dorsal aortic blood pressure (P(DA))
      without significant change in heart rate (HR). This elevation in P(DA) was
      associated with an increase in cardiac output, but systemic vascular resistance
      did not change. Intra-arterial injection of U-I (12.5-500 pmol) evoked a dose
      dependent increase in P(DA), but in contrast to the hemodynamic effects of
      centrally administered U-I, the hypertensive effect was associated with an
      increase in systemic vascular resistance and an initial fall in cardiac output.
      HR did not change or underwent a delayed increase. Pretreatment of trout with
      prazosin, an alpha-adrenoreceptor antagonist, completely abolished the rise in
      arterial blood pressure after intra-arterial administration of U-I, which was
      replaced by a sustained hypotension and tachycardia. Trout U-I produced a dose
      dependent (pD(2) = 7.74 +/- 0.08) relaxation of preconstricted rings of isolated
      trout arterial vascular smooth muscle, suggesting that the primary action of the
      peptide in the periphery is vasorelaxation that is rapidly reversed by release of
      catecholamines. Our results suggest that U-I may regulate blood pressure in trout
      by acting centrally as a neurotransmitter and/or neuromodulator and peripherally
      as a neurohormone functioning either as a locally acting vasodilator or as a
      potent secretagogue of catecholamines.

PMID- 10938237
TI  - Stress causes decrease in vascular relaxation linked with altered phosphorylation
      of heat shock proteins.
AB  - Cyclic nucleotide-dependent vascular relaxation is associated with increases in
      the phosphorylation of a small heat shock protein (HSP), HSP20. An increase in
      phosphorylation of another small HSP, HSP27, is associated with impaired cyclic
      nucleotide-dependent vascular relaxation. Expression of HSPs is altered by
      exposure to several types of cellular stress in vitro. To determine if behavioral
      stress in vivo alters vascular expression and phosphorylation of the small HSPs
      and cyclic nucleotide-dependent vascular relaxation, borderline hypertensive rats
      were stressed by restraint and exposure to air-jet stress 2 h/day for 10 days or
      remained in their home cage. Stress impaired relaxation of aorta to forskolin,
      which activates adenylyl cyclase, and sodium nitroprusside, which activates
      guanylyl cyclase. This was associated with an increase in the aortic expression
      and phosphorylation of HSP27, which was localized to the vascular smooth muscle,
      but a decrease in the amount of phosphorylated (P)-HSP20. To determine if P-HSP27
      inhibits phosphorylation of HSP20, P-HSP27 was added to a reaction mixture
      containing recombinant HSP20 and the catalytic subunit of cAMP-dependent protein
      kinase. P-HSP27 inhibited phosphorylation of HSP20 in a concentration-dependent
      manner. These data demonstrate that P-HSP27 can inhibit phosphorylation of HSP20.
      The increase in P-HSP27 and decrease in P-HSP20 were associated with reduced
      cyclic nucleotide-dependent vascular smooth muscle relaxation in response to
      behavioral stress in vivo, an effect similar to that observed previously in
      response to cellular stress in vitro.

PMID- 10938238
TI  - Activation of alpha(2)-adrenergic receptors impairs exercise-induced lipolysis in
      SCAT of obese subjects.
AB  - With the use of the microdialysis method, exercise-induced lipolysis was
      investigated in subcutaneous adipose tissue (SCAT) in obese subjects and compared
      with lean ones, and the effect of blockade of alpha(2)-adrenergic receptors (ARs)
      on lipolysis during exercise was explored. Changes in extracellular glycerol
      concentrations and blood flow were measured in SCAT in a control microdialysis
      probe at rest and during 60-min exercise bouts (50% of heart rate reserve) and in
      a probe supplemented with the alpha(2)-AR antagonist phentolamine. At rest and
      during exercise, plasma norepinephrine and epinephrine concentrations were not
      different in obese compared with lean men. In the basal state, plasma and
      extracellular glycerol concentrations were higher, whereas blood flow was lower
      in SCAT of obese subjects. During exercise, the increase of plasma glycerol was
      higher in obese subjects (115 +/- 35 vs. 65 +/- 21 micromol/l). Oppositely, the
      exercise-induced increase in extracellular glycerol concentrations in SCAT was
      five- to sixfold lower in obese than in lean subjects (50 +/- 14 vs. 318 +/- 53
      micromol/l). The exercise-induced increase in extracellular glycerol
      concentration was not significantly modified by phentolamine infusion in lean
      subjects but was strongly enhanced in the obese subjects and reached the
      concentrations found in lean sujects (297 +/- 46 micromol/l). These findings
      demonstrate that the physiological stimulation of SCAT adipocyte alpha(2)-ARs
      during exercice-induced sympathetic nervous system activation contributes to the
      blunted lipolysis noted in obese men.

PMID- 10938239
TI  - Hypothalamic adrenergic receptor changes in the metabolic syndrome of genetically
      obese (ob/ob) mice.
AB  - The genetically, seasonally, and diet-induced obese, glucose-intolerant states in
      rodents, including ob/ob mice, have each been associated with elevated
      hypothalamic levels of norepinephrine (NE). With the use of quantitative
      autoradiography on brain slices of 6-wk-old obese (ob/ob) and lean mice, the
      adrenergic receptor populations in several hypothalamic nuclei were examined. The
      binding of [(125)I]iodocyanopindolol to beta(1)- and beta(2)-adrenergic receptors
      in ob/ob mice was significantly increased in the paraventricular hypothalamic
      nucleus (PVN) by 30 and 38%, in the ventromedial hypothalamus (VMH) by 23 and
      72%, and in the lateral hypothalamus (LH) by 10 and 15%, respectively, relative
      to lean controls. The binding of [(125)I]iodo-4-hydroxyphenyl-ethyl-aminomethyl
      tetralone to alpha(1)-adrenergic receptors was also significantly increased in
      the PVN (26%), VMH (67%), and LH (21%) of ob/ob mice. In contrast, the binding of
      [(125)I]paraiodoclonidine to alpha(2)-adrenergic receptors in ob/ob mice was
      significantly decreased in the VMH (38%) and the dorsomedial hypothalamus (17%)
      relative to lean controls. This decrease was evident in the alpha(2A)- but not
      the alpha(2BC)-receptor subtype. Scatchard analysis confirmed this decreased
      density of alpha(2)-receptors in ob/ob mice. Together with earlier studies, these
      changes in hypothalamic adrenergic receptors support a role for increased
      hypothalamic NE activity in the development of the metabolic syndrome of ob/ob
      mice.

PMID- 10938240
TI  - Role of endothelin-1 in stress response in the central nervous system.
AB  - Endothelin (ET)-1 is a 21-amino acid peptide that induces a variety of biological
      activities, including vasoconstriction and cell proliferation, and its likely
      involvement in cardiovascular and other diseases has recently led to broad
      clinical trials of ET receptor antagonists. ET-1 is widely distributed in the
      central nervous system (CNS), where it is thought to regulate hormone and
      neurotransmitter release. Here we show that CNS responses to emotional and
      physical stressors are differentially affected in heterozygous ET-1-knockout
      mice, which exhibited diminished aggressive and autonomic responses toward
      intruders (emotional stressors) but responded to restraint-induced (physical)
      stress more intensely than wild-type mice. This suggests differing roles of ET-1
      in the central pathways mediating responses to different types of stress.
      Hypothalamic levels of ET-1 and the catecholamine metabolite 3-methoxy-4
      hydroxyphenylglycol (MHPG) were both increased in wild-type mice subjected to
      intruder stress, whereas MHPG levels were not significantly affected in ET-1
      knockout mice. Furthermore, immunohistochemical analysis showed that ET-1 and
      tyrosine hydroxylase, an enzyme in the catecholamine synthesis pathway, were
      colocalized within certain neurons of the hypothalamus and amygdala. Our findings
      suggest that ET-1 modulates central coordination of stress responses in close
      association with catecholamine metabolism.

PMID- 10938241
TI  - Novel expression and regulation of the renin-angiotensin system in metanephric
      organ culture.
AB  - To evaluate the presence and regulation of the renin-angiotensin system (RAS) in
      metanephric organ culture, embryonic day 14 (E14) rat metanephroi were cultured
      for 6 days. mRNAs for renin and both ANG II receptors (AT(1) and AT(2)) are
      expressed at E14, and all three genes continue to be expressed in culture. Renin
      mRNA is localized to developing tubules and ureteral branches in the cultured
      explants. At E14, renin immunostaining is found in isolated cells scattered
      within the mesenchyme. As differentiation progresses, renin localizes to the
      ureteric epithelium, developing tubules and glomeruli. E14 metanephroi contain
      ANG II, and peptide production persists in culture. Renin activity is present at
      E14 (6.13 +/- 0.61 pg ANG I. kidney(-1). h(-1)) and in cultured explants (28.84
      +/- 1. 13 pg ANG I. kidney(-1). h(-1)). Renin activity in explants is increased
      by ANG II treatment (70.1 +/- 6.36 vs. 40.97 +/- 1.94 pg ANG I. kidney(-1). h(-1)
      in control). This increase is prevented by AT(1) blockade, whereas AT(2)
      antagonism has no effect. These studies document an operational local RAS and a
      previously undescribed positive-feedback mechanism for renin generation in
      avascular, cultured developing metanephroi. This novel expression pattern and
      regulatory mechanism highlight the unique ability of developing renal cells to
      express an active RAS.

PMID- 10938242
TI  - Cardiovascular actions of python bradykinin and substance P in the anesthetized
      python, Python regius.
AB  - The cardiovascular actions of python bradykinin (BK) and substance P (SP) have
      been investigated in the anesthetized ball python, Python regius. Bolus intra
      arterial injections of python BK (0.03-3 nmol/kg) produced concentration
      dependent increases in arterial blood pressure, heart rate (HR), and cardiac
      output concomitant with small decreases in systemic resistance and stroke volume.
      Intra-arterial injection of 3 nmol/kg python BK produced a tenfold increase in
      circulating concentration of norepinephrine, but epinephrine levels did not
      change. BK-induced tachycardia was attenuated (>90%) by the beta-adrenergic
      receptor antagonist sotalol, and the hypertensive response was attenuated (>70%)
      by the alpha-adrenergic receptor antagonist prazosin, indicating that effects of
      python BK are mediated at least in part by activation of the extensive network of
      adrenergic neurons present in vascular tissues. Bolus intra-arterial injections
      of python SP in the range 0. 01-30 pmol/kg produced concentration-dependent
      decreases in arterial blood pressure and systemic peripheral resistance
      concomitant with increases in cardiac output and stroke volume but with only
      minor effects on HR. The data suggest that kinins play a physiologically
      important role in cardiovascular regulation in the python.

PMID- 10938243
TI  - Coupling of left ventricular and aortic volume elasticity in the rabbit.
AB  - Changes in volume elasticity (VE) of the left ventricle and aorta could be
      important for blood flow. A procedure is presented to rapidly assess VE of the
      left ventricle and aorta by analyzing changes in the eigenfrequency. Six control
      rabbits and 11 rabbits with atheromatosis (12 wk of high-cholesterol feeding)
      were studied. In control rabbits, during the first half of the systole, left
      ventricular VE continuously increased to +43% (P < 0.05). Then VE gradually
      declined to an end-diastolic minimum (20% of the average systolic levels, P <
      0.05). Aortic VE changes were in the opposite direction to the ventricle. Aortic
      VE continuously decreased throughout the systole; the last value was 20% lower
      than at the beginning of the systole (P < 0.05). Conversely, diastolic VE of the
      aorta took on greater values. This inverse time course between ventricle and
      aorta may reduce energy requirements for conveying blood. High cholesterol-fed
      rabbits did not reveal the inverse behavior of ventricular and aortic VE, e.g.,
      aortic VE increased during the systole (119%, P < 0.05).

PMID- 10938245
TI  - A cortisol surge mediates the enhanced polyamine synthesis in porcine enterocytes
      during weaning.
AB  - This study was conducted to determine whether a cortisol surge mediates the
      enhanced expression of intestinal ornithine decarboxylase (ODC) in weanling pigs.
      Piglets were nursed by sows until 21 days of age, when 40 pigs were randomly
      assigned into one of four groups (10 animals/group). Group 1 continued to be fed
      by sows, whereas groups 2-4 were weaned to a corn and soybean meal-based diet.
      Weanling pigs received intramuscular injections of vehicle solvent (sesame oil),
      RU-486 (a potent blocker of glucocorticoid receptors; 10 mg/kg body wt), and
      metyrapone (an inhibitor of adrenal cortisol synthesis; 5 mg/kg body wt),
      respectively, 5 min before weaning and 24 and 72 h later. At 29 days of age, pigs
      were used to prepare jejunal enterocytes for ODC assay and metabolic studies. To
      determine polyamine (putrescine, spermidine, and spermine) synthesis, enterocytes
      were incubated for 45 min at 37 degrees C in 2 ml Krebs-bicarbonate buffer
      containing 1 mM [U-(14)C]arginine, 1 mM [U-(14)C]ornithine, 1 mM [U
      (14)C]glutamine, or 1 mM [U-(14)C]proline plus 1 mM glutamine. Weaning increased
      intestinal ODC activity by 230% and polyamine synthesis from ornithine, arginine,
      and proline by 72-157%. Arginine was a quantitatively more important substrate
      than proline for intestinal polyamine synthesis in weaned pigs. Administration of
      RU-486 or metyrapone to weanling pigs prevented the increases in intestinal ODC
      activity and polyamine synthesis, reduced intracellular polyamine concentrations,
      and decreased villus heights and intestinal growth. Our results demonstrate an
      essential role for a cortisol surge in enhancing intestinal polyamine synthesis
      during weaning, which may be of physiological importance for intestinal
      adaptation and remodeling.

PMID- 10938244
TI  - Effect of single wrist exercise on fibroblast growth factor-2, insulin-like
      growth factor, and growth hormone.
AB  - Anabolic effects of exercise are mediated, in part, by fibroblast growth factor-2
      (FGF-2), insulin-like growth factor-I (IGF-I), and growth hormone (GH). To
      identify local vs. systemic modification of these mediators, 10 male subjects
      performed 10 min of unilateral wrist-flexion exercise. Blood was sampled from
      catheters placed in basilic veins of both arms. Lactate was significantly
      increased only in the exercising arm. FGF-2 decreased dramatically (P < 0.01) in
      both the resting (from 1.49 +/- 0.32 to nadir at 0.11 +/- 0.11 pg/ml) and
      exercising arm (1.80 +/- 0.60 to 0.29 +/- 0.14 pg/ml). Small but significant
      increases were found in both the resting and exercising arm for IGF-I and IGF
      binding protein-3 (IGFBP-3). GH was elevated in blood sampled from both the
      resting (from 1.04 +/- 0.68 to a peak of 2.57 +/- 0.53 ng/ml) and exercising arm
      (1.04 +/- 0.66 to 2.43 +/- 0.42 ng/ml, P < 0.05). Unilateral wrist exercise was
      not sufficiently intense to increase circulating lactate or heart rate, but it
      led to systemic changes in GH, IGF-I, IGFBP-3, and FGF-2. Low-intensity exercise
      involving small muscle groups can influence the circulating levels of growth
      factors.

PMID- 10938246
TI  - Intrapericardiac injections of algogenic chemicals excite primate C1-C2
      spinothalamic tract neurons.
AB  - Extracellular potentials of 38 C1-C2 spinothalamic tract (STT) neurons in
      anesthetized monkeys (Macaca fascicularis) were examined for responses to
      intrapericardiac injections of an algogenic chemical mixture (adenosine, 10(-3)
      M; bradykinin, prostaglandin E(2), serotonin, histamine, each 10(-5) M). Chemical
      stimulation of cardiac/pericardiac receptors increased activity of 21 cells,
      decreased activity of 5 cells, and did not change activity of 12 cells. Cells
      excited by chemical stimuli received input from noxious mechanical stimulation of
      somatic fields; most receptive fields included the neck, inferior jaw, or head
      areas. Nerve ablations in 11 cells excited by intrapericardiac chemicals showed
      that cardiac input activated by algogenic chemicals traveled primarily in vagal
      afferent fibers to C1-C2 segments; phrenic or cardiopulmonary sympathetic inputs
      were predominant in 2 of 11 cells. These results supported the concept that
      activation of cardiac vagal afferents might lead to the production of referred
      pain sensation in somatic fields innervated from high cervical segments.

PMID- 10938247
TI  - Impact of NO on ET-1- and AM-induced inotropic responses: potentiation by
      combined administration.
AB  - We characterize herein the impact of myocardial nitric oxide (NO) synthesis on
      the inotropic response to two cardioactive peptides, endothelin-1 (ET-1) and
      adrenomedullin (AM). In the isolated perfused rat heart preparation,
      intracoronary infusion of AM (0.03 and 1 nmol/l) and ET-1 (0.08 and 1 nmol/l) for
      30 min induced a dose-dependent, gradual increase in developed tension, the
      maximal responses being equal. Inhibition of myocardial NO synthase (NOS) by
      N(omega)-nitro-L-arginine methyl ester (L-NAME; 300 micromol/l) enhanced the
      inotropic response to ET-1 at a concentration of 1 nmol/l; meanwhile, the effect
      of AM was not augmented significantly. The inotropic response to simultaneous
      administration of low, equipotent doses of AM (0.03 nmol/l) and ET-1 (0.08
      nmol/l) was significantly smaller than that of either peptide alone. This
      depressed response was more than overcome by concomitant administration of L
      NAME. In conclusion, this study reveals that the maximal inotropic response to ET
      1 can be augmented by inhibition of myocardial NOS, whereas it has only a minor
      impact on the effect of AM. The inotropic response to combined administration of
      low doses of AM and ET-1 is substantially suppressed by endogenous NO, whereas
      the individual effects of the peptides at these doses are not the subject of
      secondary modulation by NO.

PMID- 10938248
TI  - Role of renin-angiotensin system in hypotension-evoked thirst: studies with
      hydralazine.
AB  - Injection of rats either with diazoxide (25 mg/kg iv), isoproterenol (0.33 mg/kg
      sc), or hydralazine (HDZ) (10 mg/kg ip) decreased arterial blood pressure from
      approximately 120 to 70-80 mmHg and stimulated renin secretion. However,
      diazoxide and isoproterenol treatments each stimulated water ingestion, whereas
      HDZ treatment did not. HDZ treatment did not reduce water intake evoked by
      systemic injection of hypertonic saline or 20% polyethylene glycol solution or by
      24-h water deprivation, suggesting that HDZ treatment did not interfere with
      drinking behavior. In contrast, HDZ treatment markedly reduced water intake
      evoked by injection of diazoxide or isoproterenol or by intravenous infusion of
      renin. Furthermore, a highly significant correlation was observed when plasma ANG
      II levels were plotted as a function of plasma renin activity after intravenous
      infusion of renin and after diazoxide and isoproterenol treatments. However,
      values obtained after HDZ treatment alone or in combination with intravenous
      infusion of renin did not fall near the 99% confidence interval of the regression
      line, suggesting that HDZ treatment blocks ANG II production and/or promotes its
      clearance. Thus rats apparently do not increase water intake after HDZ treatment,
      because this drug interferes with the renin-angiotensin system. These results
      provide further evidence that arterial hypotension evokes thirst in rats
      predominantly by activation of the renin-angiotensin system.

PMID- 10938249
TI  - Age-related changes in circadian responses to dark pulses.
AB  - Aging involves many alterations in circadian rhythms, including a loss of
      sensitivity to both photic and nonphotic time signals. This study investigated
      the sensitivity of young and old hamsters to the phase advancing effect of a 6-h
      dark pulse on the locomotor activity rhythm. Each hamster was tested four times
      during a period of approximately 9 mo; periods of exposure to a 14-h photoperiod
      were alternated with the periods of exposure to constant light (20-80 lx), during
      which the dark pulses were administered. There was no significant difference in
      the phase shifts exhibited by the young (4-10 mo) and old hamsters (19-25 mo) or
      in the amount of wheel running activity displayed during each dark pulse.
      However, young hamsters had a significantly greater propensity to exhibit split
      rhythms immediately after the dark pulses. These results suggest that, although
      aging does not reduce the sensitivity of the circadian pacemaker to this
      nonphotic signal, it alters one property of the pacemaker, i.e., the flexibility
      of the coupling of its component oscillators.

PMID- 10938250
TI  - Role of area postrema in control of torpor in Siberian hamsters.
AB  - Siberian hamsters undergo torpor during the short days of winter and in response
      to glucoprivation or food restriction. We tested whether the area postrema and
      the adjacent nucleus of the solitary tract (hereafter the AP), which monitor
      metabolic fuel availability, also control the onset of torpor. Siberian hamsters
      that had manifested torpor spontaneously or had entered torpor in response to 2
      deoxy-D-glucose (2-DG) treatment were subjected to area postrema ablations (APx).
      Hamsters continued to display torpor postoperatively; most features of torpor
      were unaffected by APx. The AP is not necessary for expression of torpor elicited
      by short day lengths or metabolic challenge. In contrast, decreases in food
      intake manifested by hamsters treated with 2-DG were counteracted by APx. In
      Siberian hamsters, the AP appears to mediate effects of 2-DG on food intake but
      not torpor.

PMID- 10938251
TI  - Identification and regional distribution of the dopamine D(1A) receptor in the
      gastrointestinal tract.
AB  - Dopamine (DA) is regarded as an important modulator of enteric function. Recent
      experiments have suggested that newly cloned DA receptor subtypes are widely
      expressed in peripheral organs, including the gastrointestinal tract. In the
      present studies, the D(1A) receptor subtype was identified in rat gut regions
      through localization of receptor protein by means of light microscopic
      immunohistochemistry and Western blot analysis and receptor mRNA by RT-PCR and in
      situ amplification and hybridization (3SR in situ). D(1A) receptor
      immunoreactivity was shown to have a diverse distribution in the gastrointestinal
      tract, being present in the gastroesophageal junction, stomach, pylorus, small
      intestine, and colon. The receptor has a transmural distribution present in both
      epithelial and muscle layers as well as in blood vessels and lamina propria cells
      of different gastrointestinal regions. Western blot analysis demonstrated a
      single 50-kDa band for esophagus, stomach, duodenum, jejunum, and colon. The in
      situ hybridization signal was localized to the same sites revealed by D(1A)
      receptor immunoreactivity. RT-PCR revealed an appropriate sized signal in similar
      regions. This study is the first to identify expression of the central D(1A)
      receptor throughout the normal mammalian gastrointestinal tract.

PMID- 10938252
TI  - Fever and motor activity in rats following day and night injections of
      Staphylococcus aureus cell walls.
AB  - Body temperature and physical activity are affected by both circadian cycles and
      pyrogens. We injected intraperitoneally 2.5 x 10(9) cell walls of the gram
      positive organism Staphylococcus aureus or sterile saline at three different
      times in the circadian temperature and activity rhythm of Sprague-Dawley rats.
      Irrespective of whether pyrogen injections were made when the rats were inactive
      (injection at 0900), just before the nighttime rise in activity and body
      temperature (1630), or during high activity (2100), the peak body temperature
      attained and the time to reach peak temperature were indistinguishable. The fever
      response, as measured by the thermal-response index, was greatest, however, when
      body temperature and activity were in the lowest phase. Physical activity was
      inhibited by night but not day injection of S. aureus. Our results provide the
      first description of experimental fever resulting from a gram-positive pyrogen in
      rats and the first time an aspect of sickness behavior (suppressed motor
      activity) has been associated with fever resulting from simulated gram-positive
      bacterial infection.

PMID- 10938253
TI  - Cardiorespiratory responses of white sturgeon to environmental hypercapnia.
AB  - Cardioventilatory variables and blood-gas, acid-base status were measured in
      cannulated white sturgeon (Acipenser transmontanus) maintained at 19 degrees C
      during normocapnic and hypercapnic (Pw(CO(2)) approximately 20 Torr) water
      conditions and after the injection of adrenergic analogs. Hypercapnia produced
      significant increases in arterial PCO(2), ventilatory frequency, and plasma
      concentration of cortisol and epinephrine, and it produced significant decreases
      in arterial pH and plasma concentration of glucose but no change in arterial
      PO(2), hematocrit, and concentration of lactate or norepinephrine. Hypercapnia
      significantly increased cardiac output (Q) by 22%, mean arterial pressure (MAP)
      by 8%, and heart rate (HR) by 8%. However, gut blood flow (GBF) remained
      constant. In normocapnic fish, phenylephrine significantly constricted the
      splanchnic circulation, whereas isoproterenol significantly increased Q and
      produced a systemic vasodilation. During hypercapnia, propranolol significantly
      decreased Q, GBF, MAP, and HR, whereas phentolamine significantly decreased MAP
      and increased GBF. These changes suggest that cardiovascular function in the
      white sturgeon is sensitive to both alpha- and beta-adrenergic modulation. We
      found microspheres to be unreliable in predicting GBF on the basis of our
      comparisons with simultaneous direct measurements of GBF. Overall, our results
      demonstrate that environmental hypercapnia (e.g., as is experienced in high
      intensity culture situations) elicits stress responses in white sturgeon that
      significantly elevate steady-state cardiovascular and ventilatory activity
      levels.

PMID- 10938254
TI  - Effects of angiotensin II on regional afferent and efferent arteriole dimensions
      and the glomerular pole.
AB  - The diversity of renal arteriole diameters in different cortical regions has
      important consequences for control of glomerular capillary pressure. We examined
      whether intrarenal angiotensin II (ANG II; 0.1, 1, or 5 ng. kg(-1). min(-1)) in
      anesthetized rabbits acts preferentially on pre- or postglomerular vessels using
      vascular casting. ANG II produced dose-related reductions in afferent and
      efferent diameters in the outer, mid, and inner cortex, without effecting
      arterial pressure. Afferent diameter decreased more than efferent in the outer
      and mid cortex (P < 0.05) but by a similar extent in juxtamedullary nephrons (P =
      0.58). Calculated efferent resistance increased more than afferent, especially in
      the outer cortex (127 vs. 24 units; 5 ng. kg(-1). min(-1) ANG II). ANG II
      produced significant dose-related increases in the distance between the
      arterioles at the entrance to the glomerular pole in all regions. Thus afferent
      diameter decreased more in response to ANG II, but efferent resistance rose more
      due to smaller resting luminal dimensions. The results also indicate that
      glomerular pole dimensions change in response to ANG II.

PMID- 10938255
TI  - Relative magnitude of tonic and phasic synaptic excitation of medullary
      inspiratory neurons in dogs.
AB  - The relative contribution of phasic and tonic excitatory synaptic drives to the
      augmenting discharge patterns of inspiratory (I) neurons within the ventral
      respiratory group (VRG) was studied in anesthetized, ventilated, paralyzed, and
      vagotomized dogs. Multibarrel micropipettes were used to record simultaneously
      single-unit neuronal activity and pressure microejected antagonists of GABAergic,
      glycinergic, N-methyl-D-aspartate (NMDA) and non-NMDA glutamatergic, and
      cholinergic receptors. The discharge patterns were quantified via cycle-trigger
      histograms. The findings suggest that two-thirds of the excitatory drive to
      caudal VRG I neurons is tonic and mediated by NMDA receptors and the other third
      is ramp-like phasic and mediated by non-NMDA receptors. Cholinergic receptors do
      not appear to be involved. The silent expiratory phase is produced by phasic
      inhibition of the tonic activity, and approximately 80% of this inhibition is
      mediated by gamma-aminobutyric acid receptors (GABA(A)) and approximately 20% by
      glycine receptors. Phasic I inhibition by the I decrementing neurons does not
      appear to contribute to the predominantly step-ramp patterns of these I neurons.
      However, this decrementing inhibition may be very prominent in controlling the
      rate of augmentation in late-onset I neurons and those with ramp patterns lacking
      the step component.

PMID- 10938256
TI  - Molecular and kinetic characterization and cell type location of inducible nitric
      oxide synthase in fish.
AB  - We have found conclusive evidence for inducible nitric oxide synthase (iNOS)
      activity in rainbow trout (Oncorhynchus mykiss) tissue by means of biochemical,
      immunohistochemical, and immunoblotting analyses. This Ca(2+)-independent enzyme
      uses L-arginine to produce nitric oxide and L-citrulline. It was significantly
      inhibited by the L-arginine analogs N(omega)-monomethyl-L-arginine and N(G)-nitro
      L-arginine methyl ester. Kinetic analyses showed typical Michaelian behavior with
      no evidence of cooperative effects. The specific activities of the liver and head
      kidney enzymes were 27 and 106 pmoles. min(-1). mg protein(-1), respectively,
      with similar values for K(m) (11 microM), all of which correspond well with the
      values for other previously characterized iNOS. Western blot analyses revealed a
      single band of M(R) = 130 kDa tested with an iNOS antiserum. At the
      ultrastructural level, cells with NADPH-diaphorase activity and iNOS
      immunoreactivity were identified as being heterophilic granulocytes in head
      kidney tissue and neutrophils and macrophages in hepatic tissue. The presence of
      an iNOS isoform in these fish tissues implies that these cells are capable of
      generating nitric oxide, thus pointing to the potential role of this enzyme in
      fish defense mechanisms.

PMID- 10938257
TI  - The biomechanics and evolutionary significance of thermal acclimation in the
      common carp Cyprinus carpio.
AB  - The effects of thermal acclimation were investigated in the common carp Cyprinus
      carpio L. Acclimation and acute temperature effects were tested during ontogeny
      from larval [9.5 mm total length (L)] to juvenile (69.0 mm L) stages and between
      8 and 21 degrees C. The myosin heavy chain (MHC) composition, myofibrillar Mg(2+)
      Ca(2+)-ATPase activity, and muscle strains showed significant thermal acclimation
      effects. MHCs were only expressed in an acclimation temperature-dependent fashion
      in fish longer than 37 mm. During fast starts, the temperature had a significant
      effect on the white muscle strain (33% increase and 50% decrease with increasing
      acclimation and acute temperature, respectively) and contraction duration (25%
      decrease with increasing acute temperature). Increases in hydrodynamic efficiency
      (0.19 to 0.38) and hydrodynamic power requirements (Q(10) = 3.2) occurred with
      increasing acute temperature (10 to 20 degrees C). Competing hypotheses about the
      evolutionary significance of the temperature acclimation response were tested.
      Acclimation extended the temperature range for fast-start behavior, but no
      improvements in performance at the whole animal level were found between 8 and 21
      degrees C.

PMID- 10938259
TI  - Parasympathetic reflex vasodilatation in rat submandibular gland.
AB  - The present study was designed to investigate 1) whether parasympathetic reflex
      vasodilatation occurs in the submandibular gland (SMG) in deeply urethan
      anesthetized, cervically vagotomized, and sympathectomized rats when the central
      cut end of the lingual nerve (LN) is electrically stimulated and 2) to what
      extent the neural mechanisms underlying such responses are the same as those
      involved in the response to direct stimulation of the chorda-LN (CLN).
      Stimulation of each nerve separately elicited a marked blood flow increase in
      SMG. Section of the chorda tympani abolished the SMG blood flow response but had
      no effect on the lip blood flow increase evoked by LN stimulation. Section of the
      CLN abolished the SMG blood flow increases evoked by stimulation of either nerve.
      The SMG blood flow increases (regardless of whether they were evoked by LN or CLN
      stimulation) were markedly reduced by the autonomic cholinergic ganglion blocker
      hexamethonium. The present study demonstrates that a parasympathetic reflex
      vasodilator mechanism is present in the rat SMG and that it can express its
      effects under deep general anesthesia.

PMID- 10938258
TI  - Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle
      against infarction.
AB  - Protein kinase C (PKC) inhibitors, chelerythrine (Chel, 0.6 mg) and polymyxin B
      (Poly B, 1.0 mg), and PKC activators, phorbol 12-myristate 13-acetate (PMA, 0.05
      mg) and 1-oleoyl-2-acetyl glycerol (OAG, 0.1 mg), were used as probes to
      investigate the role of PKC in mediation of ischemic preconditioning (IPC) of
      noncontracting pig latissimus dorsi (LD) muscles against infarction in vivo.
      These drugs were delivered to each LD muscle flap (8 x 12 cm) by 10 min of local
      intra-arterial infusion. It was observed that LD muscle flaps sustained 43 +/- 5%
      infarction when subjected to 4 h of global ischemia and 24 h of reperfusion. IPC
      with three cycles of 10 min ischemia-reperfusion reduced muscle infarction to 25
      +/- 3% (P < 0.05). This anti-infarction effect of IPC was blocked by Chel (42 +/-
      7%) and Poly B (37 +/- 2%) and mimicked by PMA (19 +/- 10%) and OAG (14 +/- 5%)
      treatments (P < 0.05), given 10 min before 4 h of ischemia. In addition, the ATP
      sensitive K(+) (K(ATP)) channel antagonist sodium 5-hydroxydecanoate attenuated
      (P < 0.05) the anti-infarction effect of IPC (37 +/- 2%), PMA (44 +/- 17%), and
      OAG (46 +/- 9%). IPC, OAG, and Chel treatment alone did not affect mean arterial
      blood pressure or muscle blood flow assessed by 15-microm radioactive
      microspheres. Western blot analysis of muscle biopsies obtained before (baseline)
      and after IPC demonstrated seven cytosol-associated isoforms, with nPKCepsilon
      alone demonstrating progressive cytosol-to-membrane translocation within 10 min
      after the final ischemia period of IPC. Using differential fractionation, it was
      observed that nPKCepsilon translocated to a membrane compartment other than the
      sarcolemma and/or sarcoplasmic reticulum. Furthermore, IPC and preischemic OAG
      but not postischemic OAG treatment reduced (P < 0.05) muscle myeloperoxidase
      activity compared with time-matched ischemic controls during 16 h of reperfusion
      after 4 h of ischemia. Taken together, these observations indicate that PKC plays
      a central role in the anti-infarction effect of IPC in pig LD muscles, most
      likely through a PKC-K(ATP) channel-linked signal-transduction pathway.

PMID- 10938260
TI  - Effects of posture on gastric emptying and satiety ratings after a nutritive
      liquid and solid meal.
AB  - To study the effects of posture and meal structure on gastric emptying and
      satiety, nine women ingested tomato soup and then immediately or 20 min later an
      egg sandwich, when seated and when supine. The lag time was not different, but
      the half-emptying time of the sandwich was 32% longer (P < 0.01) and the emptying
      rate after the lag phase was 39% slower (P < 0.01) when the subjects were supine
      than when they were seated. The half-emptying time of the soup was 50% longer (P
      < 0.01) when the subjects were supine and ingested the soup immediately before
      the sandwich than in the other three conditions. Postprandial hunger ratings
      recovered more slowly (P < 0.01) when the subjects ingested the soup 20 min
      before the sandwich than when they ingested the soup immediately before the
      sandwich. These results suggest that posture did not affect the intragastric
      distribution of the sandwich but affected propulsion of the meal into the
      intestine and that postprandial satiety was enhanced by the cumulative effect
      over time of a 20-min "head start" in stimulation of intestinal receptors by
      emptying of the soup.

PMID- 10938261
TI  - Effect of intracerebroventricular alpha-MSH on food intake, adiposity, c-Fos
      induction, and neuropeptide expression.
AB  - alpha-Melanocyte-stimulating hormone (alpha-MSH) is a hypothalamic neuropeptide
      proposed to play a key role in energy homeostasis. To investigate the behavioral,
      metabolic, and hypothalamic responses to chronic central alpha-MSH
      administration, alpha-MSH was infused continuously into the third cerebral
      ventricle of rats for 6 days. Chronic alpha-MSH infusion reduced cumulative food
      intake by 10.7% (P < 0.05 vs. saline) and body weight by 4.3% (P < 0.01 vs.
      saline), which in turn lowered plasma insulin levels by 29.3% (P < 0.05 vs.
      saline). However, alpha-MSH did not cause adipose-specific wasting nor did it
      alter hypothalamic neuropeptide mRNA levels. Central alpha-MSH infusion acutely
      activated neurons in forebrain areas such as the hypothalamic paraventricular
      nucleus, as measured by a 254% increase in c-Fos-like immunoreactivity (P < 0.01
      vs. saline), as well as satiety pathways in the hindbrain. Our findings suggest
      that, although an increase of central melanocortin receptor signaling acutely
      reduces food intake and body weight, its anorectic potency wanes during chronic
      infusion and causes only a modest decrease of body weight.

PMID- 10938262
TI  - Taurine secretion in primary monolayer cultures of flounder renal epithelium:
      stimulation by low osmolality.
AB  - Transepithelial taurine fluxes determined in short-circuited monolayer cultures
      of flounder renal proximal cells in Ussing chambers revealed net taurine
      secretion. Both unidirectional secretory and reabsorptive taurine fluxes
      exhibited saturation kinetics contributed by two distinct saturable
      transepithelial taurine transport systems operating at different taurine
      concentration ranges. The taurine secretory system operating below 0. 5 mM had
      lower affinity but higher capacity than the reabsorptive system, whereas the one
      operating at high concentrations (0.5-3.0 mM) had higher affinity but the same
      capacity as the corresponding reabsorptive system. Exposure (2 h) of the cultures
      to hyposmotic medium in the presence of taurine increased taurine secretory flux
      twofold with no effect on the reabsorptive flux. The hyposmolality-induced
      increase in taurine secretion was associated with a decreased peritubular taurine
      efflux and a concurrent increased luminal taurine efflux; the latter occurred via
      a pathway that was not affected by 4,4'-diisothiocyanostilbene-2,2'-disulfonic
      acid but inhibited by probenecid. The culture response in hyposmotic medium
      mimics the in vivo response of the intact marine fish kidney to dilution.

PMID- 10938263
TI  - Bilateral distribution of vagal motor and sensory nerve fibers in the rat's lungs
      and airways.
AB  - This study combined single and transneuronal labeling to define the origin of
      midline-crossing vagal fibers projecting to the rat's lungs. Injections of the
      beta-subunit of cholera toxin (CT-beta) into the lungs labeled similar numbers of
      neuronal somata in the nucleus ambiguus and dorsal motor nucleus of the vagus on
      both sides of the medulla, even though vagal stimulation increased lung
      resistance 50% less in the contralateral than in the ipsilateral lung. Unilateral
      cervical vagotomy prevented CT-beta labeling of ipsilateral neuronal somata and
      sensory fibers, indicating that lung-bound vagal fibers undergo decussation only
      inside the thorax. Injections of CT-beta and FluoroGold into opposite main stem
      bronchi double labeled 30% and 11% of all neuronal somata immunoreactive for CT
      beta and FluoroGold, respectively, showing that one single vagal motoneuron can
      innervate airways on both sides. Injections of pseudorabies virus into the right
      lung revealed a bilateral network of infected neurons, even after unilateral
      vagotomy. The latter did not prevent infection of the ipsilateral vagal nuclei.
      These findings demonstrate that vagal motoneurons that project to the lungs
      receive contralateral inputs from the airway premotor network and vagal
      bronchomotor centers.

PMID- 10938264
TI  - Sympathetic reflexes after depletion of bulbospinal catecholaminergic neurons
      with anti-DbetaH-saporin.
AB  - We examined the effects of destroying bulbospinal catecholaminergic neurons with
      the immunotoxin anti-dopamine beta-hydroxylase-saporin (anti-DbetaH-Sap) on
      splanchnic nerve activity (SNA) and selected sympathetic reflexes in rats. Anti
      DbetaH-Sap was administered into the thoracic spinal cord with the retrograde
      tracer fast blue. After 3-5 wk, anti-DbetaH-Sap eliminated most bulbospinal C1
      (>74%), C3 ( approximately 84%), A5 ( approximately 98%), and A6 cells.
      Noncatecholaminergic bulbospinal neurons of the rostral ventrolateral medulla and
      serotonergic neurons were spared. Under chloralose anesthesia, mean arterial
      pressure and heart rate of anti-DbetaH-Sap-treated rats (3-5 wk) were normal.
      Resting SNA was not detectably altered, but the baroreflex range and gain were
      reduced approximately 40% (P < 0.05). Phenyl biguanide-induced decreases in mean
      arterial pressure, heart rate, and SNA were unchanged by anti-DbetaH-Sap, but the
      sympathoexcitatory response to intravenous cyanide was virtually abolished (P <
      0.05). Rats that received spinal injections of saporin conjugated to an anti
      mouse IgG had intact bulbospinal C1 and A5 cells and normal physiological
      responses. These data suggest that C1 and A5 neurons contribute modestly to
      resting SNA and cardiopulmonary reflexes. However, bulbospinal catecholaminergic
      neurons appear to play a prominent sympathoexcitatory role during stimulation of
      chemoreceptors.

PMID- 10938265
TI  - Regulation of the microphthalmia-associated transcription factor gene by the
      Waardenburg syndrome type 4 gene, SOX10.
AB  - The absence of melanocytes from the cochlea and epidermis is responsible of
      deafness and hypopigmentation, two symptoms shared by the four Waardenburg
      syndrome (WS) subtypes. Microphthalmia-associated transcription factor (MITF)
      controls melanocyte survival and differentiation. Mutations, which impair MITF
      function or expression, result in an abnormal melanocyte development leading to
      the WS2. WS1 and WS3 are caused by mutation in the gene encoding the
      transcription factor Pax3, which regulates MITF expression. Recently, mutations
      in SOX10, a gene encoding a SRY-related transcription factor, have been reported
      in patients with WS4. However, the molecular basis of the defective melanocyte
      development in these patients remained to be elucidated. In the present report,
      we demonstrate that Sox10 is a strong activator of the MITF promoter, and we
      identify a Sox10 binding site between -264 and -266 of the MITF promoter.
      Finally, we show that three SOX10 mutations found in WS4 abolish the
      transcriptional activity of the resulting Sox10 proteins toward the MITF
      promoter. Taken together, our observations bring new and meaningful information
      concerning the molecular process that leads to a defective melanocyte development
      in WS4 patients with SOX10 mutations.

PMID- 10938266
TI  - Constitutive tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine secretion
      of prolactin in human breast cancer.
AB  - Overexpression of the oncogene for ErbB-2 is an unfavorable prognostic marker in
      human breast cancer. Its oncogenic potential appears to depend on the state of
      tyrosine phosphorylation. However, the mechanisms by which ErbB-2 is
      constitutively tyrosine-phosphorylated in human breast cancer are poorly
      understood. We now show that human breast carcinoma samples with ErbB-2
      overexpression have higher proliferative and metastatic activity in the presence
      of autocrine secretion of prolactin (PRL). By using a neutralizing antibody or
      dominant negative (DN) strategies or specific inhibitors, we also show that
      activation of Janus kinase Jak2 by autocrine secretion of PRL is one of the
      significant components of constitutive tyrosine phosphorylation of ErbB-2, its
      association with Grb2 and activation of mitogen-activated protein (MAP) kinase in
      human breast cancer cell lines that overexpress ErbB-2. Furthermore, the
      neutralizing anti-PRL antibody or erbB-2 antisense oligonucleotide or DN Jak2 or
      Jak2 inhibitor or DNRas or MAP kinase kinase inhibitor inhibits the proliferation
      of both untreated and PRL-treated cells. Our results indicate that autocrine
      secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides
      docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing
      unrestricted cellular proliferation. The identification of this novel cross-talk
      between ErbB-2 and the autocrine growth stimulatory loop for PRL may provide new
      targets for therapeutic and preventive intervention of human breast cancer.

PMID- 10938267
TI  - Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79
      antibody.
AB  - Sulfated forms of sialyl-Le(X) containing Gal-6-SO(4) or GlcNAc-6-SO(4) have been
      implicated as potential recognition determinants on high endothelial venule
      ligands for L-selectin. The optimal configuration of sulfate esters on the N
      acetyllactosamine (Galbeta1-->4GlcNAc) core of sulfosialyl-Le(X), however,
      remains unsettled. Using a panel of sulfated lactose (Galbeta1-->4Glc)
      neoglycolipids as substrates in direct binding assays, we found that 6',6
      disulfolactose was the preferred structure for L-selectin, although significant
      binding to 6'- and 6-sulfolactose was observed as well. Binding was EDTA
      sensitive and blocked by L-selectin-specific monoclonal antibodies. Surprisingly,
      6', 6-disulfolactose was poorly recognized by MECA-79, a carbohydrate- and
      sulfate-dependent monoclonal antibody that binds competitively to L-selectin
      ligands. Instead, MECA-79 bound preferentially to 6-sulfolactose. The difference
      in preferred substrates between L-selectin and MECA-79 may explain the variable
      activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial
      venules in lymphoid organs. Our results suggest that both Gal-6-SO(4) and GlcNAc
      6-SO(4) may contribute to L-selectin recognition, either as components of
      sulfosialyl-Le(X) capping groups or in internal structures. By contrast, only
      GlcNAc-6-SO(4) appears to contribute to MECA-79 binding.

PMID- 10938268
TI  - Novel omega-conotoxins from Conus catus discriminate among neuronal calcium
      channel subtypes.
AB  - omega-Conotoxins selective for N-type calcium channels are useful in the
      management of severe pain. In an attempt to expand the therapeutic potential of
      this class, four new omega-conotoxins (CVIA-D) have been discovered in the venom
      of the piscivorous cone snail, Conus catus, using assay-guided fractionation and
      gene cloning. Compared with other omega-conotoxins, CVID has a novel loop 4
      sequence and the highest selectivity for N-type over P/Q-type calcium channels in
      radioligand binding assays. CVIA-D also inhibited contractions of electrically
      stimulated rat vas deferens. In electrophysiological studies, omega-conotoxins
      CVID and MVIIA had similar potencies to inhibit current through central (alpha(1B
      d)) and peripheral (alpha(1B-b)) splice variants of the rat N-type calcium
      channels when coexpressed with rat beta(3) in Xenopus oocytes. However, the
      potency of CVID and MVIIA increased when alpha(1B-d) and alpha(1B-b) were
      expressed in the absence of rat beta(3), an effect most pronounced for CVID at
      alpha(1B-d) (up to 540-fold) and least pronounced for MVIIA at alpha(1B-d) (3
      fold). The novel selectivity of CVID may have therapeutic implications. (1)H NMR
      studies reveal that CVID possesses a combination of unique structural features,
      including two hydrogen bonds that stabilize loop 2 and place loop 2 proximal to
      loop 4, creating a globular surface that is rigid and well defined.

PMID- 10938269
TI  - Mutational analysis of 3' splice site selection during trans-splicing.
AB  - trans-Splicing is essential for mRNA maturation in trypanosomatids. A conserved
      AG dinucleotide serves as the 3' splice acceptor site, and analysis of native
      processing sites suggests that selection of this site is determined according to
      a 5'-3' scanning model. A series of stable gene replacement lines were generated
      that carried point mutations at or near the 3' splice site within the intergenic
      region separating CUB2.65, the calmodulin-ubiquitin associated gene, and FUS1,
      the ubiquitin fusion gene of Trypanosoma cruzi. In one stable line, the
      elimination of the native 3' splice acceptor site led to the accumulation of Y
      branched splicing intermediates, which served as templates for mapping the first
      trans-splicing branch points in T. cruzi. In other lines, point mutations shifted
      the position of the first consensus AG dinucleotide either upstream or downstream
      of the wild-type 3' splice acceptor site in this intergenic region. Consistent
      with the scanning model, the first AG dinucleotide downstream of the branch
      points was used as the predominant 3' splice acceptor site. In all of the stable
      lines, the point mutations affected splicing efficiency in this region.

PMID- 10938270
TI  - Small GTPase Rab4 regulates Ca2+-induced alpha-granule secretion in platelets.
AB  - Upon activation, platelets release many active substances stored in alpha- and
      dense-core granules. However, the molecular mechanisms governing regulated
      exocytosis are not yet fully understood. Here, we have established an assay
      system using permeabilized platelets to analyze the Ca(2+)-induced exocytosis of
      both types of granules, focusing on RabGTPases. Incubation with Rab GDP
      dissociation inhibitor, an inhibitory regulator of RabGTPases, reduced membrane
      bound RabGTPases extensively, and caused strong inhibition of the Ca(2+)-induced
      secretion of von Willebrand factor (vWF) stored in alpha-granules, but not that
      of [(3)H]5-hydroxytryptamine (5-HT) in dense-core granules. Specifically, Rab4 co
      fractionated with vWF and P-selectin (an alpha-granule marker) upon separation of
      platelet organelles by density gradient centrifugation. Incubation of the
      permeabilized platelets with cell extracts expressing the dominant negative
      mutant of His-tagged Rab4S22N, but not with those of similar mutant His
      Rab3BT36N, inhibited the vWF secretion, whereas neither of the cell extracts
      affected the [(3)H]5-HT secretion. Importantly, the inhibition of vWF secretion
      was rescued by depleting the cell extracts of the His-Rab4S22N with nickel beads.
      Thus, in platelets, the regulatory mechanisms governing alpha- and dense-core
      granule secretions are distinct, and Rab4 is an essential regulator of the Ca(2+)
      induced exocytosis of alpha-granules.

PMID- 10938271
TI  - Phosphatidylserine synthase-1 and -2 are localized to mitochondria-associated
      membranes.
AB  - We report the subcellular localization of enzymes involved in phosphatidylserine
      biosynthesis in mammalian cells. Several lines of evidence suggest that
      phosphatidylserine synthase-1 (PSS1) is highly enriched in mitochondria
      associated membranes (MAM) and is largely excluded from the bulk of the
      endoplasmic reticulum (ER). Taking advantage of the substrate specificity of
      PSS1, we showed that (i) MAM contain choline exchange activity, whereas this
      activity is very low in the bulk of the ER, (ii) serine exchange activity is
      inhibited by choline to a much greater extent in MAM than in ER, and (iii) MAM
      use phosphatidylcholine and phosphatidylethanolamine as substrates for
      phosphatidylserine biosynthesis, whereas the ER utilizes only
      phosphatidylethanolamine. According to immunoblotting of proteins from both CHO
      K1 cells and murine liver, PSS1 is localized to MAM, and in hepatoma cells stably
      expressing PSS1 this protein is highly enriched in MAM. Since the ER contains
      serine and ethanolamine exchange activities, we had predicted that PSS2 would
      account for the serine exchange activity in the ER. Unexpectedly, using
      immunoblotting experiments, we found that (i) PSS2 of CHO-K1 cells is present
      only in MAM and (ii) PSS2 is restricted to MAM of McArdle cells expressing
      recombinant PSS2. These data leave open the question of which enzyme imparts PSS
      activity to the ER and suggest that a third isoform of PSS might be located in
      the ER.

PMID- 10938272
TI  - Rapid induction of histone hyperacetylation and cellular differentiation in human
      breast tumor cell lines following degradation of histone deacetylase-1.
AB  - Quinidine inhibits proliferation and promotes cellular differentiation in human
      breast tumor epithelial cells. Previously we showed quinidine arrested MCF-7
      cells in G(1) phase of the cell cycle and led to a G(1) to G(0) transition
      followed by apoptotic cell death. The present experiments demonstrated that MCF
      7, MCF-7ras, T47D, MDA-MB-231, and MDA-MB-435 cells transiently differentiate
      before undergoing apoptosis in response to quinidine. The cells accumulated lipid
      droplets, and the cytokeratin 18 cytoskeleton was reorganized. Hyperacetylated
      histone H4 appeared within 2 h of the addition of quinidine to the medium, and
      levels were maximal by 24 h. Quinidine-treated MCF-7 cells showed elevated
      p21(WAF1), hypophosphorylation and suppression of retinoblastoma protein, and
      down-regulation of cyclin D1, similar to the cell cycle response observed with
      cells induced to differentiate by histone deacetylase inhibitors, trichostatin A,
      and trapoxin. Quinidine did not show evidence for direct inhibition of histone
      deacetylase enzymatic activity in vitro. HDAC1 was undetectable in MCF-7 cells 30
      min after addition of quinidine to the growth medium. The proteasome inhibitors
      MG-132 and lactacystin completely protected HDAC1 from the action of quinidine.
      We conclude that quinidine is a breast tumor cell differentiating agent that
      causes the loss of HDAC1 via a proteasomal sensitive mechanism.

PMID- 10938273
TI  - Identification of the elements regulating the expression of the cell adhesion
      molecule MCAM/MUC18. Loss of AP-2 is not required for MCAM expression in melanoma
      cell lines.
AB  - The cell adhesion molecule melonoma cell adhesion molecule (MCAM)/MUC18/CD146 is
      specifically up-regulated on tumors of neuroectodermal origin and in animal
      models confers metastatic capacity to human melanoma cells. To identify critical
      regions regulating MCAM expression in melanomas, 1 kilobase of the MCAM 5' region
      was analyzed for promoter activity and transcription factor binding in 1 glioma,
      1 carcinoma, and 4 melanoma cell lines. The minimal MCAM promoter (-106/+22 base
      pair (bp)) consists of 4 Sp-1 sites, two AP-2 elements, one cAMP responsive
      element, and the initiator surrounding the transcriptional start site. Analysis
      of mutated constructs indicated that the cAMP-responsive element is a major
      transcriptional activator in the majority of cell lines. Site-directed
      mutagenesis revealed that, in AP-2 expressing cells, the AP-2 site within the
      core promoter (-23 bp) has an inhibitory influence on MCAM expression while the
      AP-2 sites at -131 and -302 bp are activating. Functional AP-2 was observed in
      both MCAM positive and MCAM negative melanoma cell lines indicating that
      expression of MCAM does not require loss of this transcription factor.
      Furthermore, all MCAM constructs were strongly expressed in MCAM negative as well
      as MCAM positive cells, indicating that the expression of this gene is not
      controlled solely by the presence of transactivating factors binding to the
      investigated region.

PMID- 10938274
TI  - The homeodomain transcription factor Xvent-2 mediates autocatalytic regulation of
      BMP-4 expression in Xenopus embryos.
AB  - Like other genes of the transforming growth factor-beta family, the BMP-4 gene is
      regulated by an autocatalytic loop. In Xenopus embryos this loop can be
      ectopically induced by injection of BMP-2 RNA. However, cycloheximide treatment
      subsequent to BMP-2 overexpression revealed that BMP signaling is not direct but
      requires additional factor(s). As putative mediator we have identified Xvent-2
      which is activated by BMP-2/4 signaling and, in turn, activates BMP-4
      transcription. Using promoter/reporter assays we have delineated Xvent-2
      responsive elements within the BMP-4 gene. We further demonstrate that Xvent-2
      which has recently been characterized as a transcriptional repressor can also
      act, context dependent, as an activator binding two copies of a 5'-CTAATT-3'
      motif in the second intron of the BMP-4 gene. Replacement of Xvent-2 target sites
      within the goosecoid (gsc) promoter by the BMP-4 enhancer converts Xvent-2 caused
      repression of gsc to strong activation. This switch is obviously due to adjacent
      nucleotides probably binding a transcriptional co-activator interacting with
      Xvent-2. A model is presented describing the mechanism of BMP-4 gene activation
      in Xenopus embryos at the early gastrula stage.

PMID- 10938275
TI  - Helicobacter pylori-selective antibacterials based on inhibition of pyrimidine
      biosynthesis.
AB  - We report the discovery of a class of pyrazole-based compounds that are potent
      inhibitors of the dihydroorotate dehydrogenase of Helicobacter pylori but that do
      not inhibit the cognate enzymes from Gram-positive bacteria or humans. In culture
      these compounds inhibit the growth of H. pylori selectively, showing no effect on
      other Gram-negative or Gram-positive bacteria or human cell lines. These
      compounds represent the first examples of H. pylori-specific antibacterial
      agents. Cellular activity within this structural class appears to be due to
      dihydroorotate dehydrogenase inhibition. Minor structural changes that abrogate
      in vitro inhibition of the enzyme likewise eliminate cellular activity.
      Furthermore, the minimum inhibitory concentrations of these compounds increase
      upon addition of orotate to the culture medium in a concentration-dependent
      manner, consistent with dihydroorotate dehydrogenase inhibition as the mechanism
      of cellular inhibition. The data presented here suggest that targeted inhibition
      of de novo pyrimidine biosynthesis may be a valuable mechanism for the
      development of antimicrobial agents selective for H. pylori.

PMID- 10938276
TI  - A human gene coding for a membrane-associated nucleic acid-binding protein.
AB  - Studies to clone a cell-surface DNA-binding protein involved in the binding and
      internalization of extracellular DNA have led to the isolation of a gene for a
      membrane-associated nucleic acid-binding protein (MNAB). The full-length cDNA is
      4.3 kilobases with an open reading frame of 3576 base pairs encoding a protein of
      approximately 130 kDa (GenBank accession numbers and ). The MNAB gene is on human
      chromosome 9 with wide expression in normal tissues and tumor cells. A C3HC4 RING
      finger and a CCCH zinc finger have been identified in the amino-terminal half of
      the protein. MNAB bound DNA (K(D) approximately 4 nm) and mutagenesis of a single
      conserved amino acid in the zinc finger reduced DNA binding by 50%. A potential
      transmembrane domain exists near the carboxyl terminus. Antibodies against the
      amino-terminal half of the protein immunoprecipitated a protein of molecular mass
      approximately 150 kDa and reacted with cell surfaces. The MNAB protein is
      membrane-associated and primarily localized to the perinuclear space, probably to
      the endoplasmic reticulum or trans-Golgi network. Characterization of the MNAB
      protein as a cell-surface DNA-binding protein, critical in binding and
      internalization of extracellular DNA, awaits confirmation of its localization to
      cell surfaces.

PMID- 10938277
TI  - Interaction of the precursor to mitochondrial aspartate aminotransferase and its
      presequence peptide with model membranes.
AB  - The possible contribution of the mature portion of a mitochondrial precursor
      protein to its interaction with membrane lipids is unclear. To address this
      issue, we examined the interaction of the precursor to mitochondrial aspartate
      aminotransferase (pmAAT) and of a synthetic peptide corresponding to the 29
      residue presequence peptide (mAAT-pp) with anionic phospholipid vesicles. The
      affinity of mAAT-pp and pmAAT for anionic vesicles is nearly identical. Results
      obtained by analyzing the effect of mAAT-pp or full-length pmAAT on either the
      permeability or microviscosity of the phospholipid vesicles are consistent with
      only a shallow insertion of the presequence peptide in the bilayer. Analysis of
      the quenching of Trp-17 fluorescence by brominated phospholipids reveals that
      this presequence residue inserts to a depth of approximately 9 A from the center
      of the bilayer. Furthermore, in membrane-bound pmAAT or mAAT-pp, both Arg-8 and
      Arg-28 are accessible to the solvent. These results suggest that the presequence
      segment lies close to the surface of the membrane and that the mature portion of
      the precursor protein has little effect on the affinity or mode of binding of the
      presequence to model membranes. In the presence of vesicles, mAAT-pp adopts
      considerable alpha-helical structure. Hydrolysis by trypsin after Arg-8 results
      in the dissociation of the remaining 21-residue C-terminal peptide fragment from
      the membrane bilayer, suggesting that the N-terminal portion of the presequence
      is essential for membrane binding. Based on these results, we propose that the
      presequence peptide may contain dual recognition elements for both the lipid and
      import receptor components of the mitochondrial membrane.

PMID- 10938278
TI  - Characterization of a mutation of bacteriophage lambda integrase. Putative role
      in core binding and strand exchange for a conserved residue.
AB  - Site-specific recombination is involved in processes ranging from resolution of
      bacterial chromosome dimers to adeno-associated viral integration and is a
      versatile tool for mammalian genetics. The bacteriophage lambda-encoded site
      specific recombinase integrase (Int) is one of the best studied site-specific
      recombinases and mediates recombination via four distinct pathways. We have
      characterized a mutant version of lambda Int, IntT236I; this mutant can perform
      the bent-L pathway only, whereas the corresponding IntT236A mutant can perform
      bent-L, excision and integration pathways. Experiments with both IntT236I and
      IntT236A show that the hydroxyl group of threonine is necessary for wild-type
      recombination. Substitution of the threonine by serine leads to nearly complete
      rescue of the mutant phenotypes. In addition, our data show that the IntT236I
      mutant is defective partially due to obstructive steric interactions. Comparisons
      of crystal structures reveal that the threonine at residue 236 may play an
      important role in stabilizing recombination intermediates through solvent
      mediated protein-DNA interactions at the core-binding sites and that the hydroxyl
      group is important for effective cleavage and Holliday junction formation. Our
      data also indicate that Int contacts the core sites differently in intermediates
      assembled in excisive versus bent-L recombination.

PMID- 10938279
TI  - Crystal structure of 1-aminocyclopropane-1-carboxylate deaminase from Hansenula
      saturnus.
AB  - The pyridoxal 5'-phosphate (PLP)-dependent enzyme 1-aminocyclopropane-1
      carboxylate deaminase (ACCD) catalyzes a reaction that involves a ring opening of
      cyclopropanoid amino acid, yielding alpha-ketobutyrate and ammonia. Unlike other
      PLP-dependent enzymes, this enzyme has no alpha-hydrogen atom in the substrate.
      Thus, a unique mechanism for the bond cleavage is expected. The crystal structure
      of ACCD from Hansenula saturnus has been determined at 2.0 A resolution by the
      multiple wavelength anomalous diffraction method using mercury atoms as anomalous
      scatterers. The model was built on the electron density map, which was obtained
      by the density averaging of multiple crystal forms. The final model was refined
      to an R-factor of 22.5% and an R(free)-factor of 26.8%. The ACCD folds into two
      domains, each of which has an open twisted alpha/beta structure similar to the
      beta-subunit of tryptophan synthase. However, in ACCD, unlike in other members of
      the beta family of PLP-dependent enzymes, PLP is buried deep in the molecule. The
      structure provides the first view of the catalytic center of the cyclopropane
      ring opening.

PMID- 10938281
TI  - Separating substrate recognition from base hydrolysis in human thymine DNA
      glycosylase by mutational analysis.
AB  - Human thymine DNA glycosylase (TDG) was discovered as an enzyme that can initiate
      base excision repair at sites of 5-methylcytosine- or cytosine deamination in DNA
      by its ability to release thymine or uracil from G.T and G.U mismatches. Crystal
      structure analysis of an Escherichia coli homologue identified conserved amino
      acid residues that are critical for its substrate recognition/interaction and
      base hydrolysis functions. Guided by this revelation, we performed a mutational
      study of structure function relationships with the human TDG. Substitution of the
      postulated catalytic site asparagine with alanine (N140A) resulted in an enzyme
      that bound mismatched substrates but was unable to catalyze base removal.
      Mutation of Met-269 in a motif with a postulated role in protein-substrate
      interaction selectively inactivated stable binding of the enzyme to mismatched
      substrates but not so its glycosylase activity. These results establish that the
      structure function model postulated for the E. coli enzyme is largely applicable
      to the human TDG. We further provide evidence for G.U being the preferred
      substrate of TDG, not only at the mismatch recognition step of the reaction but
      also in base hydrolysis, and for the importance of stable complementary strand
      interactions by TDG to compensate for its comparably poor hydrolytic potential.

PMID- 10938282
TI  - Retinoic acid-dependent transforming growth factor-beta 2-mediated induction of
      MUC4 mucin expression in human pancreatic tumor cells follows retinoic acid
      receptor-alpha signaling pathway.
AB  - The MUC4 mucin is considered as the homologue of rat sialomucin complex (SMC, rat
      Muc4) due to its similar structural organization. Like SMC, MUC4 may also exist
      as two subunits: a mucin type unit known as MUC4alpha and a growth factor-like
      transmembrane subunit, MUC4beta. The expression of MUC4 in normal human pancreas
      is not detectable, but it is highly expressed in pancreatic tumor cells. In the
      present study, we investigated the regulation of MUC4 expression in human
      pancreatic tumor cells CD18/HPAF, exhibiting a high level of MUC4 transcripts and
      protein. When these cells were adapted to grow in the serum-free medium
      (CD18/HPAF-SF), the MUC4 expression was undetectable. Among several serum
      constituents, all-trans-retinoic acid (RA) induced the expression of MUC4
      transcripts in a concentration- and time-dependent manner. The RA-mediated
      increase in the level of the MUC4 transcript coincided with an increased
      expression of transforming growth factor-beta2 (TGF-beta2) transcript. The
      antagonist of the retinoic acid receptor (RAR)-alpha (Ro41-5253) abrogated the
      expression of MUC4 and TGF-beta2 induced by RA. The exogenous addition of TGF
      beta2 also increased the MUC4 expression. The TGF-beta-neutralizing antibody
      blocked the RA-induced as well as TGF-beta2-mediated MUC4 expression. In
      conclusion, induction of MUC4 expression in pancreatic carcinoma by RA is
      mediated through the RAR-alpha signaling pathway, and TGF-beta2 may serve as an
      interim mediator of this regulated expression.

PMID- 10938283
TI  - Stress pathway activation induces phosphorylation of retinoid X receptor.
AB  - Cellular stresses inhibit retinoid signaling, but the molecular basis for this
      phenomenon has not been revealed. Here, we present evidence that retinoid X
      receptor (RXR) is a substrate for both mitogen-activated protein kinase kinase-4
      (MKK4/SEK1) and its downstream mediator c-Jun N-terminal kinase (JNK). MKK4/SEK1
      and JNK recognized distinct features on RXR in the DE and AB regions,
      respectively. Phosphorylation by MKK4/SEK1 had profound effects on the
      biochemical properties of RXR, inhibiting the expression of genes activated by
      RXR-retinoic acid receptor complexes. Tyr-249 in the RXR DE region was required
      for the inhibitory effect of MKK4/SEK1. These effects were significantly reduced
      in MKK4/SEK1-null cells, indicating that MKK4/SEK1 is required for the
      suppression of retinoid signaling by stress. Findings presented here demonstrate
      that MKK4/SEK1 can directly modulate transcription by phosphorylating RXR, a
      novel MKK4/SEK1 substrate.

PMID- 10938284
TI  - The human synaptotagmin IV gene defines an evolutionary break point between
      syntenic mouse and human chromosome regions but retains ligand inducibility and
      tissue specificity.
AB  - Rat synaptotagmin IV (SYT IV) is a depolarization-inducible synaptic vesicle
      protein. SYT IV homozygous mutant mice are viable and have deficits in fine motor
      coordination and some forms of memory. In this study, we report the
      identification of a human SYT IV orthologue. The predicted amino acid sequence of
      the human SYT IV clone is nearly 90% identical to the rat and mouse SYT IV
      proteins. In addition, human SYT IV has a characteristic serine for aspartate
      substitution within the first C2 domain that is conserved among Drosophila,
      Caenorhabditis elegans, mouse, and rat SYT IV sequences. The human SYT IV gene
      maps to chromosome band 18q12.3, a region that defines a break point in the
      synteny with mouse chromosome 18 and has been implicated by associated markers in
      two human psychiatric disorders. In the human neuroblastoma cell line SK-N-SH,
      SYT IV is an immediate-early gene inducible by elevated intracellular calcium and
      by forskolin, an activator of adenylyl cyclase. Expression of human SYT IV mRNA
      is restricted to brain and is not detectable in non-neuronal tissues. Within
      brain, human SYT IV mRNA is most highly expressed in hippocampus, with lower
      levels present in amygdala and thalamus. These results suggest a role for SYT IV
      in human brain function and in human neurological disease.

PMID- 10938285
TI  - BRCA1 facilitates stress-induced apoptosis in breast and ovarian cancer cell
      lines.
AB  - The BRCA1 tumor suppressor gene has previously been implicated in induction of
      high levels of apoptosis in osteocarcinoma cell lines. Overexpression of BRCA1
      was shown to induce an apoptotic signaling pathway involving the c-Jun N-terminal
      kinase (JNK), but the signaling steps upstream and downstream of JNK were not
      delineated. To better understand the role of BRCA1 in apoptosis, we examined the
      effect of wild-type and C-terminal-truncated dominant negative BRCA1 on breast
      and ovarian cancer cell lines subjected to a number of different pro-apoptotic
      stimuli, including growth factor withdrawal, substratum detachment, ionizing
      radiation, and treatment with anticancer agents. All of these treatments were
      found to induce substantial levels of apoptosis in the presence of wild-type
      BRCA1, whereas dominant negative BRCA1 truncation mutants diminished the
      apoptotic response. Subsequent mapping of the apoptotic pathway induced by growth
      factor withdrawal demonstrated that BRCA1 enhanced signaling through a pathway
      that sequentially involved H-Ras, MEKK4, JNK, Fas ligand/Fas interactions, and
      caspase-9 activation. In addition, the pathway functioned independently of the
      p53 tumor suppressor. These data suggest that BRCA1 is an important modulator of
      the response to cellular stress and that loss of this apoptotic potential due to
      BRCA1 mutations may contribute to tumor development.

PMID- 10938286
TI  - C-terminal domain phosphatase sensitivity of RNA polymerase II in early
      elongation complexes on the HIV-1 and adenovirus 2 major late templates.
AB  - The fate of RNA polymerase II in early elongation complexes is under the control
      of factors that regulate and respond to the phosphorylation state of the C
      terminal domain (CTD). Phosphorylation of the CTD protects early elongation
      complexes from negative transcription elongation factors such as NELF, DSIF, and
      factor 2. To understand the relationship between transcript elongation and the
      sensitivity of RNA polymerase IIO to dephosphorylation, elongation complexes at
      defined positions on the Ad2-ML and human immunodeficiency virus type 1 (HIV-1)
      templates were purified, and their sensitivity to CTD phosphatase was determined.
      Purified elongation complexes treated with 1% Sarkosyl and paused at U(14)/G(16)
      on an HIV-1 template and at G(11) on the Ad2-ML template are equally sensitive to
      dephosphorylation by CTD phosphatase. Multiple elongation complexes paused at
      more promoter distal sites are more resistant to dephosphorylation than are
      U(14)/G(16) and G(11) complexes. The HIV-1 long terminal repeat and adenovirus 2
      major late promoter do not appear to differentially influence the CTD phosphatase
      sensitivity of stringently washed complexes. Subsequent elongation by 1% Sarkosyl
      washed U(14)/G(16) complexes is unaffected by prior CTD phosphatase treatment.
      This result is consistent with the hypothesis that CTD phosphatase requires the
      presence of specific elongation factors to propagate a negative effect on
      transcript elongation. The action of CTD phosphatase on elongation complexes is
      inhibited by HIV-1 Tat protein. This observation is consistent with the idea that
      Tat suppression of CTD phosphatase plays a role in transactivation.

PMID- 10938287
TI  - Mismatch recognition and DNA-dependent stimulation of the ATPase activity of
      hMutSalpha is abolished by a single mutation in the hMSH6 subunit.
AB  - The most abundant mismatch binding factor in human cells, hMutSalpha, is a
      heterodimer of hMSH2 and hMSH6, two homologues of the bacterial MutS protein. The
      C-terminal portions of all MutS homologues contain an ATP binding motif and are
      highly conserved throughout evolution. Although the N termini are generally
      divergent, they too contain short conserved sequence elements. A phenylalanine -
      > alanine substitution within one such motif, GXFY(X)(5)DA, has been shown to
      abolish the mismatch binding activity of the MutS protein of Thermus aquaticus
      (Malkov, V. A., Biswas, I., Camerini-Otero, R. D., and Hsieh, P. (1997) J. Biol.
      Chem. 272, 23811-23817). We introduced an identical mutation into one or both
      subunits of hMutSalpha. The Phe --> Ala substitution in hMSH2 had no effect on
      the biological activity of the heterodimer. In contrast, the in vitro mismatch
      binding and mismatch repair functions of hMutSalpha were severely attenuated when
      the hMSH6 subunit was mutated. Moreover, this variant heterodimer also displayed
      a general DNA binding defect. Correspondingly, its ATPase activity could not be
      stimulated by either heteroduplex or homoduplex DNA. Thus the N-terminal portion
      of hMSH6 appears to impart on hMutSalpha not only the specificity for recognition
      and binding of mismatched substrates but also the ability to bind to homoduplex
      DNA.

PMID- 10938288
TI  - Demonstration of functional requirement of polypyrimidine tract-binding protein
      by SELEX RNA during hepatitis C virus internal ribosome entry site-mediated
      translation initiation.
AB  - Polypyrimidine tract-binding protein (PTB) has been previously shown to
      physically interact with the hepatitis C virus (HCV) RNA genome at its 5'- and 3'
      noncoding regions. Using high affinity SELEX RNA molecules, we present evidence
      for the functional requirement of PTB during HCV internal ribosome entry site
      (IRES)-controlled translation initiation. This study was carried out in rabbit
      reticulocyte translation lysates in which the HCV IRES-driven reporter RNA was
      introduced along with the PTB-specific SELEX RNA molecules. The SELEX RNAs
      specifically inhibited the HCV IRES function in the context of mono- and
      dicistronic mRNAs. The cap-dependent translation of a reporter (chloramphenicol
      acetyltransferase) RNA or naturally capped brome mosaic virus RNA, however, was
      not affected by the presence of SELEX during in vitro translation assays. The
      SELEX-mediated inhibition of the HCV IRES is shown to be relieved by the addition
      of recombinant human PTB in an add-back experiment. The in vivo requirement of
      PTB was further confirmed by cotransfection of Huh7 cells with reporter RNA and
      PTB-specific SELEX RNA. The HCV IRES activity was inhibited by the SELEX RNA in
      these cells, but not by an unrelated control RNA. Together, these results
      demonstrate the functional requirement of cellular PTB in HCV translation and
      further support the feasible use of SELEX RNA strategy in demonstrating the
      functional relevance of cellular protein(s) in complex biological processes.

PMID- 10938289
TI  - Form switching during human locomotion: traversing wedges in a single step.
AB  - We examined the neural control strategies used to accommodate discrete
      alterations in walking surface inclination. Normal subjects were tested walking
      on a level surface and on different wedges (10 degrees, 15 degrees, 20 degrees,
      and 30 degrees ) presented in the context of level walking. On a given trial, a
      subject walked on a level surface in approach to a wedge, took a single step on
      the wedge, and continued walking on an elevated level surface beyond the wedge.
      As wedge inclination increased, subjects linearly increased peak joint angles.
      Changes in timing of peak joint angles and electromyograms were not linear.
      Subjects used two distinct temporal strategies, or forms, to traverse the wedges.
      One form was used for walking on a level surface and on the 10 degrees wedge,
      another form for walking on the 20 degrees and 30 degrees wedges. In the level/10
      degrees form, peak hip flexion occurred well before heel strike (HS) and peak
      dorsiflexion occurred in late stance. In the 20 degrees /30 degrees form, peak
      hip flexion was delayed by 12% of the stride cycle and peak dorsiflexion was
      reached 12% earlier. For the level/10 degrees form, onsets of the rectus femoris,
      gluteus maximus, and vastus lateralis muscles were well before HS and offset of
      the anterior tibialis was at HS. For the 20 degrees /30 degrees form, onsets of
      the rectus femoris, gluteus maximus, and vastus lateralis and offset of the
      anterior tibialis were all delayed by 12% of the stride cycle. Muscles shifted as
      a group, rather than individually, between the forms. Subjects traversing a 15
      degrees wedge switched back and forth between the two forms in consecutive
      trials, suggesting the presence of a transition zone. Differences between the
      forms can be explained by the differing biomechanical constraints imposed by the
      wedges. Steeper wedges necessitate changes in limb orientation to accommodate the
      surface, altering limb orientation with respect to gravity and making it
      necessary to pull the body forward over the foot. The use of different forms of
      behavior is a common theme in neural control and represents an efficient means of
      coordinating and adapting movement to meet changing environmental demands. The
      forms of locomotion reported here are likely used on a regular basis in real
      world settings.

PMID- 10938290
TI  - Superficial dorsal horn neurons identified by intracutaneous histamine:
      chemonociceptive responses and modulation by morphine.
AB  - We have investigated whether neurons in superficial laminae of the spinal dorsal
      horn respond to intracutaneous (ic) delivery of histamine and other irritant
      chemicals, and thus might be involved in signaling sensations of itch or
      chemogenic pain. Single-unit recordings were made from superficial lumbar dorsal
      horn neurons in pentobarbital sodium-anesthetized rats. Chemoresponsive units
      were identified using ic microinjection of histamine (3%, 1 microl) into the
      hindpaw as a search stimulus. All superficial units so identified [9 nociceptive
      specific (NS), 26 wide-dynamic-range (WDR)] responded to subsequent ic histamine.
      A comparison group of histamine-responsive deep dorsal horn neurons (n = 16) was
      similarly identified. The mean histamine-evoked discharge decayed to 50% of the
      maximal rate significantly more slowly for the superficial (92.2 s +/- 65.5, mean
      +/- SD) compared with deep dorsal horn neurons (28. 2 s +/- 11.6). In addition to
      responding to histamine, most superficial dorsal horn neurons were also excited
      by ic nicotine (22/25 units), capsaicin (21/22), topical mustard oil (5/6),
      noxious heat (26/30), and noxious and/or innocuous mechanical stimuli (except for
      1 unit that did not have a mechanosensitive receptive field). Application of a
      brief noxious heat stimulus during the response to ic histamine evoked an
      additive response in all but two cases, followed by transient depression of
      firing in 11/20 units. Intrathecal (IT) administration of morphine had mixed
      effects on superficial dorsal horn neuronal responses to ic histamine and noxious
      heat. Low morphine concentrations (100 nM to 1 microM) facilitated histamine
      evoked responses (to >130% of control) in 9/24 units, depressed the responses (by
      >70%) in 11/24, and had no effect in 4. Naloxone reversed morphine-induced
      effects in some but not all cases. A higher morphine concentration (10 microM)
      had a largely depressant, naloxone-reversible effect on histamine responses.
      Responses of the same superficial neurons to noxious heat were facilitated
      (15/25), reduced (8/25), or unaffected (2/25) by low morphine concentrations and
      were depressed by the higher morphine concentration. In contrast, deep dorsal
      horn neuronal responses to both histamine and noxious heat were primarily
      depressed by low concentrations of morphine in a naloxone-reversible manner.
      These results indicate that superficial dorsal horn neurons respond to both
      pruritic and algesic chemical stimuli and thus might participate in transmitting
      sensations of itch and/or chemogenic pain. The facilitation of superficial
      neuronal responses to histamine by low concentrations of morphine, coupled with
      inhibition of deep dorsal horn neurons, might underlie the development of
      pruritus that is often observed after epidural morphine.

PMID- 10938291
TI  - Neural representation of salts in the rat solitary nucleus: brain stem correlates
      of taste discrimination.
AB  - One mechanism of salt taste transduction by gustatory receptor cells involves the
      influx of cations through epithelial sodium channels that can be blocked by oral
      application of amiloride. A second mechanism is less clearly defined but seems to
      depend on electroneutral diffusion of the salt through the tight junctions
      between receptor cells; this paracellular pathway is insensitive to amiloride.
      Because the first mechanism is more sensitive to sodium salts and the second to
      nonsodium salts, these peripheral events could underlie the ability of rats to
      discriminate sodium from nonsodium salts on the basis of taste. Behavioral
      experiments indicate that amiloride, at concentrations that are tasteless to
      rats, impairs a rat's ability to discriminate NaCl from KCl and may do so by
      making both salts taste like KCl. In the present study, we examined the neural
      representation of NaCl and KCl (0.05-0.2 M), and mixtures of these salts with
      amiloride (0, 3, and 30 microM), to explore the neural correlates of this
      behavioral result. NaCl and KCl were represented by distinct patterns of activity
      in the nucleus of the solitary tract. Amiloride, in a concentration-dependent
      manner, changed the pattern for NaCl to one more characteristic of KCl, primarily
      by reducing activity in neurons responding best to NaCl and sucrose. The effect
      of amiloride concentration on the response to 0.1 M NaCl in NaCl-best neurons was
      virtually identical to its effect on behavioral discrimination performance.
      Modeling the effects of blocking the amiloride-insensitive pathway also resulted
      in highly similar patterns of activity for NaCl and KCl. These results suggest
      that activity in both the amiloride-sensitive and -insensitive pathways is
      required for the behavioral discrimination between NaCl and KCl. In the context
      of published behavioral data, the present results suggest that amiloride
      sensitive activity alone is not sufficient to impart a unique signal for the
      taste of sodium salts.

PMID- 10938292
TI  - Role of muscle pulleys in producing eye position-dependence in the angular
      vestibuloocular reflex: a model-based study.
AB  - It is well established that the head and eye velocity axes do not always align
      during compensatory vestibular slow phases. It has been shown that the eye
      velocity axis systematically tilts away from the head velocity axis in a manner
      that is dependent on eye-in-head position. The mechanisms responsible for
      producing these axis tilts are unclear. In this model-based study, we aimed to
      determine whether muscle pulleys could be involved in bringing about these
      phenomena. The model presented incorporates semicircular canals, central
      vestibular pathways, and an ocular motor plant with pulleys. The pulleys were
      modeled so that they brought about a rotation of the torque axes of the
      extraocular muscles that was a fraction of the angle of eye deviation from
      primary position. The degree to which the pulleys rotated the torque axes was
      altered by means of a pulley coefficient. Model input was head velocity and
      initial eye position data from passive and active yaw head impulses with fixation
      at 0 degrees, 20 degrees up and 20 degrees down, obtained from a previous
      experiment. The optimal pulley coefficient required to fit the data was
      determined by calculating the mean square error between data and model
      predictions of torsional eye velocity. For active head impulses, the optimal
      pulley coefficient varied considerably between subjects. The median optimal
      pulley coefficient was found to be 0.5, the pulley coefficient required for
      producing saccades that perfectly obey Listing's law when using a two-dimensional
      saccadic pulse signal. The model predicted the direction of the axis tilts
      observed in response to passive head impulses from 50 ms after onset. During
      passive head impulses, the median optimal pulley coefficient was found to be
      0.21, when roll gain was fixed at 0.7. The model did not accurately predict the
      alignment of the eye and head velocity axes that was observed early in the
      response to passive head impulses. We found that this alignment could be well
      predicted if the roll gain of the angular vestibuloocular reflex was modified
      during the initial period of the response, while pulley coefficient was
      maintained at 0.5. Hence a roll gain modification allows stabilization of the
      retinal image without requiring a change in the pulley effect. Our results
      therefore indicate that the eye position-dependent velocity axis tilts could
      arise due to the effects of the pulleys and that a roll gain modification in the
      central vestibular structures may be responsible for countering the pulley
      effect.

PMID- 10938293
TI  - Memory activity of LIP neurons for sequential eye movements simulated with neural
      networks.
AB  - Many neurons in macaque lateral intraparietal cortex (LIP) maintain elevated
      activity induced by visual or auditory targets during tasks in which monkeys are
      required to withhold one or more planned eye movements. We studied the mechanisms
      for such memory activity with neural network modeling. Recurrent connections
      among simulated LIP neurons were used to model memory responses of LIP neurons.
      The connection weights were computed using an optimization procedure to produce
      desired outputs in memory-saccade tasks. One constraint for the training process
      is the "single-purpose" rule, which mimics the fact that once LIP neurons hold
      the memory activity of a saccade, they are insensitive to further stimuli until
      the motor action is completed. After training, excitatory connections were
      developed between units with similar preferred saccade directions, while
      inhibitory connections were formed between units with dissimilar directions. This
      "push-pull" mechanism enables the network to encode the next intended eye
      movement and is essential for programming sequential saccades. In simulating
      double saccades, the push-pull connections locked the on-going activity in the
      network for the first saccade until the saccade was made, then a new population
      of units became active to prepare for the second saccade. The simulated LIP
      neurons exhibited sensory responses and memory activities similar to those
      recorded in LIP neurons. We propose that push-pull recurrent connections might be
      the basic structure mediating the memory activity of area LIP in planning
      sequential eye movements.

PMID- 10938294
TI  - Subcellular localization and complements of GABA(A) and GABA(C) receptors on
      bullfrog retinal bipolar cells.
AB  - gamma-Aminobutyric acid (GABA) receptors on retinal bipolar cells (BCs) are
      highly relevant to spatial and temporal integration of visual signals in the
      outer and inner retina. In the present work, subcellular localization and
      complements of GABA(A) and GABA(C) receptors on BCs were investigated by whole
      cell recordings and local drug application via multi-barreled puff pipettes in
      the bullfrog retinal slice preparation. Four types of the BCs (types 1-4) were
      identified morphologically by injection of Lucifer yellow. According to the
      ramification levels of the axon terminals and the responses of these cells to
      glutamate (or kainate) applied at their dendrites, types 1 and 2 of BCs were
      supposed to be OFF type, whereas types 3 and 4 of BCs might be ON type.
      Bicuculline (BIC), a GABA(A) receptor antagonist, and imidazole-4-acetic acid
      (I4AA), a GABA(C) receptor antagonist, were used to distinguish GABA receptor
      mediated responses. In all BCs tested, not only the axon terminals but also the
      dendrites showed high GABA sensitivity mediated by both GABA(A) and GABA(C)
      receptors. Subcellular localization and complements of GABA(A) and GABA(C)
      receptors at the dendrites and axon terminals were highly related to the
      dichotomy of OFF and ON BCs. In the case of OFF BCs, GABA(A) receptors were
      rather evenly distributed at the dendrites and axon terminals, but GABA(C)
      receptors were predominantly expressed at the axon terminals. Moreover, the
      relative contribution of GABA(C) receptors to the axon terminals was prevalent
      over that of GABA(A) receptors, while the situation was reversed at the
      dendrites. In the case of ON BCs, GABA(A) and GABA(C) receptors both preferred to
      be expressed at the axon terminals; relative contributions of these two GABA
      receptor subtypes to both the sites were comparable, while GABA(C) receptors were
      much less expressed than GABA(A) receptors. GABA(A), but not GABA(C) receptors,
      were expressed clusteringly at axons of a population of BCs. In a minority of
      BCs, I4AA suppressed the GABA(C) responses at the dendrites, but not at the axon
      terminal, implying that the GABA(C) receptors at these two sites may be
      heterogeneous. Taken together, these results suggest that GABA(A) and GABA(C)
      receptors may play different roles in the outer and inner retina and the
      differential complements of the two receptors on OFF and ON BCs may be closely
      related to physiological functions of these cells.

PMID- 10938295
TI  - Visual, saccade-related, and cognitive activation of single neurons in monkey
      extrastriate area V3A.
AB  - Area V3A is an extrastriate visual area that provides a major input to parietal
      cortex. To identify the sensory, saccade-related, and cognitive signals carried
      by V3A neurons, we recorded from single units in alert monkeys during performance
      of fixation and memory guided saccade tasks. We found that visual responses to
      stationary stimuli in area V3A were affected by the behavioral relevance of the
      stimulus. The amplitude of the visual response differed between the memory-guided
      saccade task, in which the monkey had to use the information provided by the
      stimulus to guide its behavior, and the fixation task. For 18% (29/163) of V3A
      neurons, the response was significantly enhanced in the memory-guided saccade
      task as compared with that in the fixation task. For 8% (13/163) of V3A neurons,
      the amplitude of response in the memory-guided saccade task was significantly
      suppressed. We also observed task-related modulation of activity prior to
      stimulus onset. Among the V3A neurons (37/163) that showed significant
      differences between tasks in prestimulus activity, the majority (89%; 33/37)
      showed greater prestimulus activity in the memory-guided saccade task. Task
      related increases in prestimulus activity in the memory-guided saccade task were
      not always matched by increases in the sensory response, indicating that visual
      responses and prestimulus activity can be modulated independently. Activity in
      the memory period was suppressed compared with prestimulus activity for 83%
      (49/59) of the V3A neurons that showed a significant difference in activity
      (59/197) between these two epochs. For some neurons, memory-period activity
      dropped even below the baseline level in the fixation task, indicating that there
      may be an active suppression mechanism. Many V3A neurons (75%, 148/197) also had
      activity in the saccade epoch. This activity was most prominent immediately after
      the saccade. Postsaccadic activity was observed even when testing was carried out
      in total darkness, indicating that this activity reflects, at least in part,
      extraretinal signals and is not simply a response to visual reafference. These
      results indicate that several kinds of signals are carried by single neurons in
      extrastriate area V3A. Moreover, activity in V3A is subject to modulation by
      extraretinal factors, including attention, anticipation, memory, and saccadic eye
      movements.

PMID- 10938296
TI  - Competitive inhibition of NMDA receptor-mediated currents by extracellular
      calcium chelators.
AB  - Calcium chelators have been widely used in electrophysiological recordings of N
      methyl-D-aspartate (NMDA) receptor-mediated currents, as well as in studies of
      excitotoxicity. Intracellularly applied calcium chelators are known to inhibit,
      at least in part, such calcium-dependent processes as calmodulin-dependent
      inactivation, calcineurin-dependent desensitization, and rundown of NMDA
      receptors. On the other hand, the functional consequences and potential
      nonspecific effects of extracellularly applied chelators have not been
      extensively investigated. In whole-cell patch-clamp recordings from human
      embryonic kidney (HEK) 293 cells transiently transfected with recombinant NMDA
      receptors, we found that addition of calcium chelators such as EGTA shifted the
      glutamate dose-response curve to the right, from an EC(50) for NR1A/NR2A of 8
      microM in 1.8 mM Ca(2+) to approximately 24 microM in a solution containing
      nominal 0 Ca(2+)/5 mM EGTA and further to approximately 80 microM in 20 mM EGTA.
      A similar shift in glutamate dose-response was observed for NR1A/NR2B currents.
      This dose-response shift was not due to a decrease in extracellular Ca(2+)
      concentration because there was no change in the glutamate EC(50) at Ca(2+)
      concentrations ranging from 10 mM to nominal 0/200 microM EGTA. Moreover,
      addition of 5 mM EGTA fully chelated with 6.8 mM Ca(2+) did not produce any shift
      in the glutamate dose-response curve. We propose that calcium chelators,
      containing four free carboxyl moieties, competitively inhibit glutamate binding
      to NMDA receptors.

PMID- 10938297
TI  - Striking differences in transmission of corticospinal excitation to upper limb
      motoneurons in two primate species.
AB  - There is considerable debate as to the relative importance, for cortical control
      of upper limb movements, of direct cortico-motoneuronal (CM) versus indirect,
      propriospinal transmission of corticospinal excitation to cervical motoneurons.
      In the cat, which has no CM connections, a significant proportion of
      corticospinal excitation reaches forelimb motoneurons via a system of C(3)-C(4)
      propriospinal neurons (PN). In contrast, in the macaque monkey most motoneurons
      receive direct CM connections, and, under the same experimental conditions as in
      the cat, there is little evidence for PN transmission. We have investigated
      corticospinal transmission in the New World squirrel monkey (Saimiri sciureus)
      because its CM projections are weaker than in the macaque. Intracellular
      recordings were made from motoneurons identified from the ulnar, median, and deep
      radial (DR) nerves in four adult squirrel monkeys under chloralose anesthesia and
      neuromuscular paralysis. Responses to stimulation of the contralateral medullary
      pyramid were recorded before and after a lesion to the dorsolateral funiculus
      (DLF) at C(5), designed to interrupt direct corticospinal inputs to the lower
      cervical segments and unmask PN-mediated effects. This lesion greatly reduced the
      proportion of motoneurons showing either CM EPSPs or disynaptic IPSPs, but the
      proportion showing late EPSPs with segmental latencies beyond the monosynaptic
      range, evoked by repetitive but not single PT stimuli, was unaffected: 23 of 29
      motoneurons (79%) before and 32 of 37 (86%) after the lesion; 41% of these late
      EPSPs had strictly disynaptic latencies after the lesion, only 14% before. These
      results are in striking contrast to the macaque (late EPSPs in only 18% of
      motoneurons before a C(5) lesion, 19% after it). Transmission of the late EPSPs
      via C(3)-C(4) PNs in the squirrel monkey was indicated by their absence after an
      additional C(2) DLF lesion. Nearly all tested motoneurons also responded with
      short latency EPSPs to stimulation in the ipsilateral lateral reticular nucleus.
      By analogy with the cat, these EPSPs probably reflect antidromic activation of
      ascending collaterals of C(3)-C(4) PNs with monosynaptic connections to
      motoneurons; the EPSPs were significantly smaller than in the cat but larger than
      in the macaque. These results suggest that the positive correlation across
      species between more advanced hand function and the strength of the CM system is
      accompanied by a negative correlation between hand function and the strength of
      the PN system. We hypothesize that in primates with more advanced hand function,
      the CM system effectively replaces PN-mediated control. This would include a
      contribution to the control of reaching movements, which are said to be
      specifically under the control of the PN system in the cat, and we speculate that
      these differences may be related to the degree of dexterity exhibited by the
      different species. This interpretation of the results predicts that in man, where
      the CM system is highly developed, the PN system is unlikely to be responsible
      for significant transmission of cortical commands to upper limb motoneurons.

PMID- 10938298
TI  - alpha-SNS produces the slow TTX-resistant sodium current in large cutaneous
      afferent DRG neurons.
AB  - In this study, we used sensory neuron specific (SNS) sodium channel gene knockout
      (-/-) mice to ask whether SNS sodium channel produces the slow Na(+) current
      ("slow") in large (>40 microm diam) cutaneous afferent dorsal root ganglion (DRG)
      neurons. SNS wild-type (+/+) mice were used as controls. Retrograde Fluoro-Gold
      labeling permitted the definitive identification of cutaneous afferent neurons.
      Prepulse inactivation was used to separate the fast and slow Na(+) currents.
      Fifty-two percent of the large cutaneous afferent neurons isolated from SNS (+/+)
      mice expressed only fast-inactivating Na(+) currents ("fast"), and 48% expressed
      both fast and slow Na(+) currents. The fast and slow current densities were 0.90
      +/- 0.12 and 0.39 +/- 0.16 nA/pF, respectively. Fast Na(+) currents were blocked
      completely by 300 nM tetrodotoxin (TTX), while slow Na(+) currents were resistant
      to 300 nM TTX, confirming that the slow Na(+) currents observed in large
      cutaneous DRG neurons are TTX-resistant (TTX-R). Slow Na(+) currents could not be
      detected in large cutaneous afferent neurons from SNS (-/-) mice; these cells
      expressed only fast Na(+) current, and it was blocked by 300 nM TTX. The fast
      Na(+) current density in SNS (-/-) neurons was 1.47 +/- 0. 14 nA/pF,
      approximately 60% higher than the current density observed in SNS (+/+) mice (P <
      0.02). A low-voltage-activated TTX-R Na(+) current ("persistent") observed in
      small C-type neurons is not present in large cutaneous afferent neurons from
      either SNS (+/+) or SNS (-/-) mice. These results show that the slow TTX-R Na(+)
      current in large cutaneous afferent DRG is produced by the SNS sodium channel.

PMID- 10938299
TI  - Response properties and organization of nociceptive neurons in area 1 of monkey
      primary somatosensory cortex.
AB  - The organization and response properties of nociceptive neurons in area 1 of the
      primary somatosensory cortex (SI) of anesthetized monkeys were examined. The
      receptive fields of nociceptive neurons were classified as either wide-dynamic
      range (WDR) neurons that were preferentially responsive to noxious mechanical
      stimulation, or nociceptive specific (NS) that were responsive to only noxious
      stimuli. The cortical locations and the responses of the two classes of neurons
      were compared. An examination of the neuronal stimulus-response functions
      obtained during noxious thermal stimulation of the glabrous skin of the foot or
      the hand indicated that WDR neurons exhibited significantly greater sensitivity
      to noxious thermal stimuli than did NS neurons. The receptive fields of WDR
      neurons were significantly larger than the receptive fields of NS neurons.
      Nociceptive SI neurons were somatotopically organized. Nociceptive neurons with
      receptive fields on the foot were located more medial in area 1 of SI than those
      with receptive fields on the hand. In the foot representation, the recording
      sites of nociceptive neurons were near the boundary between areas 3b and 1,
      whereas in the hand area, there was a tendency for them to be located more caudal
      in area 1. The majority of nociceptive neurons were located in the middle layers
      (III and IV) of area 1. The fact that nociceptive neurons were not evenly
      distributed across the layers of area 1 suggested that columns of nociceptive
      neurons probably do not exist in the somatosensory cortex. In electrode tracks
      where nociceptive neurons were found, approximately half of all subsequently
      isolated neurons were also classified as nociceptive. Low-threshold
      mechanoreceptive (LTM) neurons were intermingled with nociceptive neurons. Both
      WDR and NS neurons were found in close proximity to one another. In instances
      where the receptive field shifted, subsequently isolated cells were also
      classified as nociceptive. These data suggest that nociceptive neurons in area 1
      of SI are organized in vertically orientated aggregations or clusters in layers
      III and IV.

PMID- 10938300
TI  - Responses to continuously changing optic flow in area MST.
AB  - We studied the temporal behavior and tuning properties of medial superior
      temporal (MST) neurons in response to constant flow-field stimulation and
      continuously changing flow-field stimulation (transitions), which were obtained
      by morphing one flow field into another. During transitions, the flow fields
      resembled the motion pattern seen by an observer during changing ego-motion. Our
      aim was to explore the behavior of MST cells in response to changes in the flow
      field pattern and to establish whether the responses of MST cells are temporally
      independent or if they are affected by contextual information from preceding
      stimulation. We first tested whether the responses obtained during transitions
      were linear with respect to the two stimuli defining the transition. In over half
      of the transitions, the cell response was nonlinear: the response during the
      transition could not be predicted by the linear interpolation between the
      stimulus before and after the transition. Nonlinearities in the responses could
      arise from a dependence on temporal context or from nonlinearities in the tuning
      to flow-field patterns. To distinguish between these two hypotheses, we fit the
      responses during transitions and during continuous stimuli to the predictions of
      a temporally independent model (temporal-independence test) and we compared the
      responses during transitions to the responses elicited by inverse transitions
      (temporal-symmetry test). The effect of temporal context was significant in only
      7.2% and 5.5% of cells in the temporal-independence test and in the temporal
      symmetry test, respectively. Most of the nonlinearities in the cell responses
      could be accounted for by nonlinearities in the tuning to flow-field stimuli
      (i.e., the responses to a restricted set of flow fields did not predict the
      responses to other flow fields). Tuning nonlinearities indicate that a complete
      characterization of the tuning properties of MST neurons cannot be obtained by
      testing only a small number of flow fields. Because the cells' responses do not
      depend on temporal context, continuously changing stimulation can be used to
      characterize the receptive field properties of cells more efficiently than
      constant stimulation. Temporal independence in the responses to transitions
      indicates that MST cells do not code for second-order temporal properties of flow
      field stimuli, i.e., for changes in the flow field through time that can be
      construed as paths through the environment. Information about ego-motion three
      dimensional paths through the environment may either be processed at the
      population level in MST or in other cortical areas.

PMID- 10938301
TI  - Synaptic actions of neuropeptide FF in the rat parabrachial nucleus: interactions
      with opioid receptors.
AB  - The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF
      (NPFF) projections from the lower brain stem and/or the spinal cord. Because of
      this anatomical convergence and previous evidence that NPFF displays both pro-
      and anti-opioid activities, this study examined the synaptic effects of NPFF in
      the PBN and the mechanisms underlying these effects using an in vitro brain slice
      preparation and the nystatin-perforated patch-clamp recording technique. Under
      voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory
      postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not
      accompanied by apparent changes in the holding current, the current-voltage
      relationship or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced
      inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF
      increased the ratio of these synaptic currents. Analysis of miniature EPSCs
      showed that NPFF caused a rightward shift in the frequency-distribution curve,
      whereas the amplitude-distribution curve remained unchanged. Collectively, these
      experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic
      mechanism of action. The synaptic effects induced by NPFF (5 microM) could not be
      blocked by the specific mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Arg
      Thr-Pen-Thr-NH(2) (1 microM), but application of delta-opioid receptor antagonist
      Tyr-Tic-Phe-Phe (5 microM) almost completely prevented effects of NPFF. Moreover,
      the delta-opioid receptor agonist, Deltorphin (1 microM), mimicked the effects as
      NPFF and also occluded NPFF's actions on synaptic currents. These results
      indicate that NPFF modulates excitatory synaptic transmission in the PBN through
      an interaction with presynaptic delta-opioid receptors. These observations
      provide a cellular basis for NPFF enhancement of the antinociceptive effects
      consequent to central activation of delta-opioid receptors.

PMID- 10938302
TI  - NT-3 evokes an LTP-like facilitation of AMPA/kainate receptor-mediated synaptic
      transmission in the neonatal rat spinal cord.
AB  - Neurotrophin-3 (NT-3) is a neurotrophic factor required for survival of muscle
      spindle afferents during prenatal development. It also acts postsynaptically to
      enhance the monosynaptic excitatory postsynaptic potential (EPSP) produced by
      these fibers in motoneurons when applied over a period of weeks to the axotomized
      muscle nerve in adult cats. Similar increases in the amplitude of the
      monosynaptic EPSP in motoneurons are observed after periodic systemic treatment
      of neonatal rats with NT-3. Here we show an acute action of NT-3 in enhancing the
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA/kainate) receptor
      mediated fast monosynaptic EPSP elicited in motoneurons by dorsal root (DR)
      stimulation in the in vitro hemisected neonatal rat spinal cord. The receptor
      tyrosine kinase inhibitor K252a blocks this action of NT-3 as does the calcium
      chelator bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA) injected into
      the motoneuron. The effect of NT-3 resembles long-term potentiation (LTP) in that
      transient bath application of NT-3 to the isolated spinal cord produces a long
      lasting increase in the amplitude of the monosynaptic EPSP. An additional
      similarity is that activation of N-methyl-D-aspartate (NMDA) receptors is
      required to initiate this increase but not to maintain it. The NMDA receptor
      blocker MK-801, introduced into the motoneuron through the recording
      microelectrode, blocks the effect of NT-3, indicating that NMDA receptors in the
      motoneuron membrane are crucial. The effect of NT-3 on motoneuron NMDA receptors
      is demonstrated by its enhancement of the depolarizing response of the motoneuron
      to bath-applied NMDA in the presence of tetrodotoxin (TTX). The potentiating
      effects of NT-3 do not persist beyond the first postnatal week. In addition,
      EPSPs with similar properties evoked in the same motoneurons by stimulation of
      descending fibers in the ventrolateral funiculus (VLF) are not modifiable by NT-3
      even in the initial postnatal week. Thus, NT-3 produces synapse-specific and age
      dependent LTP-like enhancement of AMPA/kainate receptor-mediated synaptic
      transmission in the spinal cord, and this action requires the availability of
      functional NMDA receptors in the motoneuron.

PMID- 10938303
TI  - Cocaine and kindling alter the sensitivity of group II and III metabotropic
      glutamate receptors in the central amygdala.
AB  - G-protein-coupled metabotropic glutamate receptors (mGluRs) are being implicated
      in various forms of neuroplasticity and CNS disorders. This study examined
      whether the sensitivities of mGluR agonists are modulated in a distinct fashion
      in different models of synaptic plasticity, specifically, kindling and chronic
      cocaine treatment. The influence of kindling and chronic cocaine exposure in vivo
      was examined in vitro on the modulation of synaptic transmission by group II and
      III metabotropic glutamate receptors using whole cell voltage-clamp recordings of
      central amygdala (CeA) neurons. Synaptic transmission was evoked by electrical
      stimulation of the basolateral amygdala (BLA) and ventral amygdaloid pathway
      (VAP) afferents in brain slices from control rats and from rats treated with
      cocaine or exposed to three to five stage-five kindled seizures. This study shows
      that after chemical stimulation with chronic cocaine exposure or after electrical
      stimulation with kindling the receptor sensitivities for mGluR agonists are
      altered in opposite ways. In slices from control rats, group II agonists,
      (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (LCCG1) and (+)-2
      aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), depressed
      neurotransmission more potently at the BLA-CeA than at the VAP-CeA synapse while
      group III agonist, L(+)-2-amino-4-phosphonobutyrate (LAP4), depressed
      neurotransmission more potently at the VAP-CeA synapse than at the BLA-CeA. These
      agonist actions were not seen (were absent) in amygdala neurons from chronic
      cocaine-treated animals. In contrast, after kindling, concentration response
      relationships for LCCG1 and LAP4 were shifted to the left, suggesting that
      sensitivity to these agonists is increased. Except at high concentrations, LCCG1,
      LY354740, and LAP4 neither induced membrane currents nor changed current-voltage
      relationships. Loss of mGluR inhibition with chronic cocaine treatment may
      contribute to counter-adaptive changes including anxiety and depression in
      cocaine withdrawal. Drugs that restore the inhibitory effects of group II and III
      mGluRs may be novel tools in the treatment of cocaine dependence. The enhanced
      sensitivity to group II and III mGluR agonists in kindling is similar to that
      recorded at the lateral to BLA synapse in the amygdala where they reduce
      epileptiform bursting. These findings suggest that drugs modifying mGluRs may
      prove useful in the treatment of cocaine withdrawal or epilepsy.

PMID- 10938304
TI  - Postsynaptic receptor occupancy during evoked transmission at striatal GABAergic
      synapses in vitro.
AB  - The effect of benzodiazepines (BZs) on GABA(A)-ergic synaptic responses depends
      on the control receptor occupancy: the BZ-induced enhancement of receptor
      affinity can lead to greater peak amplitudes of quantal responses only when,
      under normal conditions, receptors are not fully saturated at peak. Based on this
      fact, receptor occupancy at the peak of spontaneous miniature inhibitory
      postsynaptic currents (mIPSCs) has been assessed in various mammalian neuronal
      preparations. To use the same principle with compound (or multiquantal), action
      potential-evoked IPSCs, complications introduced by quantal asynchrony in
      conjunction with the BZ-induced increase in the decay time of the quantal
      responses have to be overcome. We used a simple analytic convolution model to
      calculate expected changes in the rise time and amplitude of postsynaptic
      currents when the decay time constant, but not the peak amplitude, of the
      underlying quantal responses is increased, this being the expected BZ effect at
      saturated synapses. Predictions obtained were compared with the effect of the BZ
      flunitrazepam on IPSCs recorded in paired pre- and postsynaptic whole cell
      voltage-clamp experiments on striatal neurons in cell culture. In 22 pairs,
      flunitrazepam (500 nM) reliably prolonged the decay of IPSCs (49 +/- 19%, mean +/
      SE) and in 18 of 22 cases produced an enhancement in their peak amplitude that
      varied markedly between 3 and 77% of control (26.0 +/- 5.3%). The corresponding
      change in rise time, however (+0.38 +/- 0.11 ms, range -0.8 to +1.3 ms) was far
      smaller than calculated for the observed changes in peak amplitude assuming fixed
      quantal size. Because therefore an increase in quantal size is required to
      explain our findings, postsynaptic GABA(A) receptors were most likely not
      saturated during impulse-evoked transmission at these unitary connections. The
      peak amplitudes of miniature IPSCs in these neurons were also increased by
      flunitrazepam (500 nM, +26.8 +/- 6.6%), and their decay time constant was
      increased by 26.3 +/- 7.3%. Using these values in our model led to a slight
      overestimate of the change in compound IPSC amplitude (+28 to +30%).

PMID- 10938305
TI  - Response patterns in second somatosensory cortex (SII) of awake monkeys to
      passively applied tactile gratings.
AB  - This experiment explored the effects of controlled manipulations of three
      parameters of tactile gratings, groove width (1.07-2.53 mm), contact force (30-90
      g), and scanning speed (40-120 mm/s), on the responses of cells in second
      somatosensory cortex (SII) of awake monkeys that were performing a groove-width
      classification task with passively presented stimuli. A previous experiment
      involving an active touch paradigm demonstrated that macaque SII cells code
      groove-width and hand-movement parameters in their average firing rates. The
      present study used a passive-touch protocol to remove somatosensory activation
      related to hand movements that accompany haptic exploration of surfaces. Monkeys
      maintained a constant hand position while a robotic device delivered stimulation
      with tactile gratings to a single stabilized finger pad. Single-unit recordings
      isolated 216 neurons that were retrospectively assigned to SII on histological
      criteria. Firing patterns for 86 of these SII cells were characterized in detail,
      while monkeys classified gratings as rough (1.90 and 2.53 mm groove widths) or
      smooth (1.07 and 1.42 mm groove widths), with trial-wise random, parametric
      manipulation of force or speed; the monkeys compared 1.07 versus 1.90 mm and 1.42
      versus 2.53 mm in alternating blocks of trials. We studied 33 cells with
      systematic variation of groove width and force, 49 with groove width and speed,
      and four with all three variables. Sixty-three cells were sensitive to groove
      width, 43 to force (effects of random force in speed experiments contributed to
      N), and 34 to speed. Relatively equal numbers of cells changed mean firing rates
      as positive or negative functions of increasing groove width, force, and/or
      speed. Cells typically changed mean firing rates for two or three of the
      independent variables. Effects of groove width, force, and speed were additive or
      interactive. The variety of response functions was similar to that found in a
      prior study of primary somatosensory cortex (SI) that used passive touch. The SII
      sample population showed correlated changes (both positive and negative) in
      firing rates with increasing groove width and force and to a lesser degree, with
      increasing groove width and speed. This correlation is consistent with human
      psychophysical studies that found increasing groove width and force increase
      perceived roughness magnitude, and it strengthens the argument for SII's direct
      involvement in roughness perception.

PMID- 10938306
TI  - Perfusion of the mechanically compressed lumbar ganglion with lidocaine reduces
      mechanical hyperalgesia and allodynia in the rat.
AB  - The rat L(5) dorsal root ganglion (DRG) was chronically compressed by inserting a
      hollow perforated rod into the intervertebral foramen. The DRG was constantly
      perfused through the hollow rod with either lidocaine or normal saline delivered
      by a subcutaneous osmotic pump. Behavioral evidence for neuropathic pain after
      DRG compression involved measuring the incidence of hindlimb withdrawals to both
      punctate indentations of the hind paw with mechanical probes exerting different
      bending forces (hyperalgesia) and to light stroking of the hind paw with a cotton
      wisp (tactile allodynia). Behavioral results showed that for saline-treated
      control rats: the withdrawal thresholds for the ipsilateral and contralateral
      paws to mechanical stimuli decreased significantly after surgery and the
      incidence of foot withdrawal to light stroking significantly increased on both
      ipsilateral and contralateral hind paws. Local perfusion of the compressed DRG
      with 2% lidocaine for 7 days at a low flow-rate (1 microl/h), or for 1 day at a
      high flow-rate (8 microl/h) partially reduced the decrease in the withdrawal
      thresholds on the ipsilateral foot but did not affect the contralateral foot. The
      incidence of foot withdrawal in response to light stroking with a cotton wisp
      decreased significantly on the ipsilateral foot and was completely abolished on
      the contralateral foot in the lidocaine treatment groups. This study demonstrated
      that compression of the L(5) DRG induced a central pain syndrome that included
      bilateral mechanical hyperalgesia and tactile allodynia. Results also suggest
      that a lidocaine block, or a reduction in abnormal activity from the compressed
      ganglia to the spinal cord, could partially reduce mechanical hyperalgesia and
      tactile allodynia.

PMID- 10938307
TI  - Hyperpolarization-activated, mixed-cation current (I(h)) in octopus cells of the
      mammalian cochlear nucleus.
AB  - Octopus cells in the posteroventral cochlear nucleus of mammals detect the
      coincidence of synchronous firing in populations of auditory nerve fibers and
      convey the timing of that coincidence with great temporal precision. Earlier
      recordings in current clamp have shown that two conductances contribute to the
      low input resistance and therefore to the ability of octopus cells to encode
      timing precisely, a low-threshold K(+) conductance and a hyperpolarization
      activated mixed-cation conductance, g(h). The present experiments describe the
      properties of g(h) in octopus cells as they are revealed under voltage clamp with
      whole-cell, patch recordings. The hyperpolarization-activated current, I(h), was
      blocked by extracellular Cs(+) (5 mM) and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl
      6-(methylamino) pyridinium chloride (50-100 nM) but not by extracellular Ba(2+)
      (2 mM). The reversal potential for I(h) in octopus cells under normal
      physiological conditions was -38 mV. Increasing the extracellular potassium
      concentration from 3 to 12 mM shifted the reversal potential to -26 mV; lowering
      extracellular sodium concentration from 138 to 10 mM shifted the reversal
      potential to -77 mV. These pharmacological and ion substitution experiments show
      that I(h) in octopus cells is a mixed-cation current that resembles I(h) in other
      neurons and in heart muscle cells. Under control conditions when cells were
      perfused intracellularly with ATP and GTP, I(h) had an activation threshold
      between about -35 to -40 mV and became fully activated at -110 mV. The maximum
      conductance associated with hyperpolarizing voltage steps to -112 mV ranged from
      87 to 212 nS [150 +/- 30 (SD) nS, n = 36]. The voltage dependence of g(h)
      obtained from peak tail currents is fit by a Boltzmann function with a half
      activation potential of -65 +/- 3 mV and a slope factor of 7. 7 +/- 0.7. This
      relationship reveals that g(h) was activated 41% at the mean resting potential of
      octopus cells, -62 mV, and that at rest I(h) contributes a steady inward current
      of between 0.9 and 2.1 nA. The voltage dependence of g(h) was unaffected by the
      extracellular application of dibutyryl cAMP but was shifted in hyperpolarizing
      direction, independent of the presence or absence of dibutyryl cAMP, by the
      removal of intracellular ATP and GTP.

PMID- 10938308
TI  - MST responses to pursuit across optic flow with motion parallax.
AB  - Self-movement creates the patterned visual motion of optic flow with a focus of
      expansion (FOE) that indicates heading direction. During pursuit eye movements,
      depth cues create a retinal flow field that contains multiple FOEs, potentially
      complicating heading perception. Paradoxically, human heading perception during
      pursuit is improved by depth cues. We have studied medial superior temporal (MST)
      neurons to see whether their heading selectivity is also improved under these
      conditions. The responses of 134 MST neurons were recorded during the
      presentation of optic flow stimuli containing one or three speed-defined depth
      planes. During pursuit, multiple depth-plane stimuli evoked larger responses (71%
      of neurons) and stronger heading selectivity (70% of neurons). Responses to the
      three speed-defined depth-planes presented separately showed that most neurons
      (54%) preferred one of the planes. Responses to multiple depth-plane stimuli were
      larger than the averaged responses to the three component planes, suggesting
      enhancing interactions between depth-planes. Thus speed preferences create
      selective responses to one of many depth-planes in the retinal flow field. The
      presence of multiple depth-planes enhances those responses. These properties
      might improve heading perception during pursuit and contribute to relative depth
      perception.

PMID- 10938309
TI  - Localization and contractile properties of intrinsic longitudinal motor units of
      the rat tongue.
AB  - Tongue dysfunction is a hallmark of many human clinical disorders, yet we lack
      even a rudimentary understanding of tongue neural control. Here, the location and
      contractile properties of intrinsic longitudinal motor units (MUs) of the rat
      tongue body are described to provide a foundation for developing and testing
      theories of tongue motor control. One hundred and sixty-five MUs were studied by
      microelectrode penetration and stimulation of individual motor axons coursing in
      the terminal portion of the lateral (retrusor) branch of the hypoglossal nerve in
      the rat. Uniaxial MU force was recorded by a transducer attached to the protruded
      tongue tip, and MU location was estimated by electromyographic (EMG) electrodes
      implanted into the anterior, middle, and posterior portions of the tongue body.
      All MUs produced retrusive force. MU twitch force ranged from 2-129 mg (mean = 35
      mg) and tetanic force ranged from 9-394 mg (mean = 95 mg). MUs reached maximal
      twitch force in 8-33 ms (mean = 15 ms) and were resistant to fatigue; following 2
      min of stimulation, MUs (n = 11) produced 78-131% of initial force. EMG data were
      collected for 105 MUs. For 65 of these MUs, the EMG response was confined to a
      single electrode location: for 26 MUs to the anterior, 21 MUs to the middle, and
      18 MUs to the posterior portion of the tongue. Of the remaining MUs, EMG
      responses were observed in two (38/40) or all three (2/40) tongue regions. These
      data provide the first contractile measures of identified intrinsic tongue body
      MUs and the first evidence that intrinsic longitudinal MUs are restricted to a
      portion of tongue length. Localization of MU territory suggests a role for
      intrinsic MU in the regional control of the mammalian tongue observed during
      feeding and speech.

PMID- 10938310
TI  - Mechanosensitive potassium channels in rat colon sensory neurons.
AB  - Single-channel recording techniques were used to characterize mechanosensitive
      channels in identified (1.1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine
      methanesulfonate labeled) colon sensory neurons dissociated from adult S1 dorsal
      root ganglia. Channels were found in 30% (7/23) of patches in a cell-attached
      configuration and in 43% (48/111) of excised inside-out patches. Channels were
      highly selective for K(+), had a slope conductance of 54 pS in symmetrical
      solutions, and were blocked by tetraethylammonium, amiloride, and benzamil.
      Channels were also seen under Ca(2+)-free conditions. Gadolinium (Gd(3+)), a
      known blocker of mechanosensitive ion channels, did not block channel activity.
      Tetrodotoxin and 4-aminopyridine were also ineffective. The cytoskeletal
      disrupters colchicine and cytochalasin D reduced the percentage of patches
      containing mechanosensitive channels. These results indicate that rat colon
      sensory neurons contain K(+)-selective mechanosensitive channels that may
      modulate the membrane excitability induced by colonic distension.

PMID- 10938311
TI  - Neural responses in the inferior colliculus to binaural masking level differences
      created by inverting the noise in one ear.
AB  - We have measured the responses of inferior colliculus neurons in the anesthetized
      guinea pig to signals which in human psychophysical experiments reveal a release
      of masking as a result of binaural processing (the binaural masking level
      difference: BMLD). More specifically we have used diotic tones at 500 Hz (So)
      masked by noise that is either identical at the two ears (No) or inverted in one
      ear (Npi). This combination of signals and noise maskers produces a prominent
      masking release in humans such that the So signal is about 6-12 dB more
      detectable in the presence of the Npi noise than the No noise. Low-frequency
      inferior colliculus neurons are sensitive to the interaural delay of the masking
      noise and generally respond most to the components nearest their best frequency.
      Since most inferior colliculus neurons have peaks in their delay functions close
      to zero interaural time delay this means that while No noise is effective in
      driving the unit, Npi noise is much less effective. As the level of an So tone
      was progressively increased in the presence of No and Npi noises, the first
      response could be either an increase or a decrease in the activity due to the
      noise. However, because Npi generated little or no activity itself, the
      predominant response to the So tone was an increase in discharge in this
      condition. Masked thresholds were defined as the point at which the standard
      separation D (related to the d' of signal detection theory) = 1 in either
      direction. BMLDs were measured in single neurons and in the majority of units
      were in a direction consistent with the psychophysical observations irrespective
      of the direction of the discharge rate change that occurred at threshold. The
      lowest masked thresholds always occurred at or near the signal frequency of 500
      Hz. An average value of the single unit BMLD around 500 Hz was 3.6 dB (NoSo vs.
      NpiSo) compared with 6.6 dB for the NoSo versus NoSpi BMLD we had previously
      reported. This lower magnitude is consistent with the hierarchy of human
      psychophysical BMLDs.

PMID- 10938312
TI  - Persistence of motor adaptation during constrained, multi-joint, arm movements.
AB  - We studied the stability of changes in motor performance associated with
      adaptation to a novel dynamic environment during goal-directed movements of the
      dominant arm. Eleven normal, human subjects made targeted reaching movements in
      the horizontal plane while holding the handle of a two-joint robotic manipulator.
      This robot was programmed to generate a novel viscous force field that perturbed
      the limb perpendicular to the desired direction of movement. Following adaptation
      to this force field, we sought to determine the relative role of kinematic errors
      and dynamic criteria in promoting recovery from the adapted state. In particular,
      we compared kinematic and dynamic measures of performance when kinematic errors
      were allowed to occur after removal of the viscous fields, or prevented by
      imposing a simulated, mechanical "channel" on movements. Hand forces recorded at
      the handle revealed that when kinematic errors were prevented from occurring by
      the application of the channel, recovery from adaptation to the novel field was
      much slower compared with when kinematic aftereffects were allowed to take place.
      In particular, when kinematic errors were prevented, subjects persisted in
      generating large forces that were unnecessary to generate an accurate reach. The
      magnitude of these forces decreased slowly over time, at a much slower rate than
      when subjects were allowed to make kinematic errors. This finding provides strong
      experimental evidence that both kinematic and dynamic criteria influence motor
      adaptation, and that kinematic-dependent factors play a dominant role in the
      rapid loss of adaptation after restoring the original dynamics.

PMID- 10938313
TI  - Time course and magnitude of movement-related gating of tactile detection in
      humans. II. Effects of stimulus intensity.
AB  - This study examined the effect of systematically varying stimulus intensity on
      the time course and magnitude of movement-related gating of tactile detection and
      scaling in 17 human subjects trained to perform a rapid abduction of the right
      index finger (D2) in response to a visual cue. Electrical stimulation was
      delivered to D2 at five different intensities. At the lowest intensity,
      approximately 90% of stimuli were detected at rest (1 x P(90)); four multiples of
      this intensity were also tested (1.25, 1.5, 1.75, and 2. 0 x P(90)). At all
      intensities of stimulation, detection of stimuli applied to the moving digit was
      diminished significantly and in a time-dependent manner, with peak decreases
      occurring within +/-12 ms of the onset of electromyographic activity in the first
      dorsal interosseous (25-45 ms before movement onset). Reductions in the
      proportion of stimuli detected were greatest at the lowest stimulus intensity and
      progressively smaller at higher intensities. No shift in the timing of the
      decreases in performance was seen with increasing intensity. Once the weakest
      intensity at which most stimuli were perceived during movement had been
      established (2 x P(90)), magnitude estimation experiments were performed using
      two stimulus intensities, 2 x P(90) (5 subjects) and 3 x P(90) (3 subjects).
      Significant movement-related decreases in estimated stimulus magnitude were
      observed at both intensities, the time course of which was similar to the time
      course of reductions in detection performance. As stimulus intensity increased,
      the magnitude of the movement-related decrease in scaling diminished. A model of
      detection performance that accurately described the effect of stimulus intensity
      and timing on movement-related reductions in detection was created. This model
      was then combined with a previous model that described the effects of stimulus
      localization and timing to predict detection performance at a given stimulation
      site, intensity, and time during movement. Movement-related gating of tactile
      perception represents the end result of movement-related effects on the
      transmission and subsequent processing of the stimulus. The combined model
      clearly defines many of the requirements that proposed physiological mechanisms
      of movement-related gating will have to fulfill.

PMID- 10938314
TI  - Discharge properties of neurons in the rostral superior colliculus of the monkey
      during smooth-pursuit eye movements.
AB  - The intermediate and deep layers of the monkey superior colliculus (SC) comprise
      a retinotopically organized map for eye movements. The rostral end of this map,
      corresponding to the representation of the fovea, contains neurons that have been
      referred to as "fixation cells" because they discharge tonically during active
      fixation and pause during the generation of most saccades. These neurons also
      possess movement fields and are most active for targets close to the fixation
      point. Because the parafoveal locations encoded by these neurons are also
      important for guiding pursuit eye movements, we studied these neurons in two
      monkeys as they generated smooth pursuit. We found that fixation cells exhibit
      the same directional preferences during pursuit as during small saccades-they
      increase their discharge during movements toward the contralateral side and
      decrease their discharge during movements toward the ipsilateral side. This
      pursuit-related activity could be observed during saccade-free pursuit and was
      not predictive of small saccades that often accompanied pursuit. When we plotted
      the discharge rate from individual neurons during pursuit as a function of the
      position error associated with the moving target, we found tuning curves with
      peaks within a few degrees contralateral of the fovea. We compared these pursuit
      related tuning curves from each neuron to the tuning curves for a saccade task
      from which we separately measured the visual, delay, and peri-saccadic activity.
      We found the highest and most consistent correlation with the delay activity
      recorded while the monkey viewed parafoveal stimuli during fixation. The
      directional preferences exhibited during pursuit can therefore be attributed to
      the tuning of these neurons for contralateral locations near the fovea. These
      results support the idea that fixation cells are the rostral extension of the
      buildup neurons found in the more caudal colliculus and that their activity
      conveys information about the size of the mismatch between a parafoveal stimulus
      and the currently foveated location. Because the generation of pursuit requires a
      break from fixation, the pursuit-related activity indicates that these neurons
      are not strictly involved with maintaining fixation. Conversely, because activity
      during the delay period was found for many neurons even when no eye movement was
      made, these neurons are also not obligatorily related to the generation of a
      movement. Thus the tonic activity of these rostral neurons provides a potential
      position-error signal rather than a motor command-a principle that may be
      applicable to buildup neurons elsewhere in the SC.

PMID- 10938315
TI  - Activation and inactivation of rostral superior colliculus neurons during smooth
      pursuit eye movements in monkeys.
AB  - Neurons in the intermediate and deep layers of the rostral superior colliculus
      (SC) of monkeys are active during attentive fixation, small saccades, and smooth
      pursuit eye movements. Alterations of SC activity have been shown to alter
      saccades and fixation, but similar manipulations have not been shown to influence
      smooth-pursuit eye movements. Therefore we both activated (electrical
      stimulation) and inactivated (reversible chemical injection) rostral SC neurons
      to establish a causal role for the activity of these neurons in smooth pursuit.
      First, we stimulated the rostral SC during pursuit initiation as well as pursuit
      maintenance. For pursuit initiation, stimulation of the rostral SC suppressed
      pursuit to ipsiversive moving targets primarily and had modest effects on
      contraversive pursuit. The effect of stimulation on pursuit varied with the
      location of the stimulation with the most rostral sites producing the most
      effective inhibition of ipsiversive pursuit. Stimulation was more effective on
      higher pursuit speeds than on lower and did not evoke smooth-pursuit eye
      movements during fixation. As with the effects on pursuit initiation, ipsiversive
      maintained pursuit was suppressed, whereas contraversive pursuit was less
      affected. The stimulation effect on smooth pursuit did not result from a
      generalized inhibition because the suppression of smooth pursuit was greater than
      the suppression of smooth eye movements evoked by head rotations (vestibular
      ocular reflex). Nor was the stimulation effect due to the activation of
      superficial layer visual neurons rather than the intermediate layers of the SC
      because stimulation of the superficial layers produced effects opposite to those
      found with intermediate layer stimulation. Second, we inactivated the rostral SC
      with muscimol and found that contraversive pursuit initiation was reduced and
      ipsiversive pursuit was increased slightly, changes that were opposite to those
      resulting from stimulation. The results of both the stimulation and the muscimol
      injection experiments on pursuit are consistent with the effects of these
      activation and inactivation experiments on saccades, and the effects on pursuit
      are consistent with the hypothesis that the SC provides a position signal that is
      used by the smooth-pursuit eye-movement system.

PMID- 10938316
TI  - Orientation tuning of input conductance, excitation, and inhibition in cat
      primary visual cortex.
AB  - The input conductance of cells in the cat primary visual cortex (V1) has been
      shown recently to grow substantially during visual stimulation. Because
      increasing conductance can have a divisive effect on the synaptic input,
      theoretical proposals have ascribed to it specific functions. According to the
      veto model, conductance increases would serve to sharpen orientation tuning by
      increasing most at off-optimal orientations. According to the normalization
      model, conductance increases would control the cell's gain, by being independent
      of stimulus orientation and by growing with stimulus contrast. We set out to test
      these proposals and to determine the visual properties and possible synaptic
      origin of the conductance increases. We recorded the membrane potential of cat V1
      cells while injecting steady currents and presenting drifting grating patterns of
      varying contrast and orientation. Input conductance grew with stimulus contrast
      by 20-300%, generally more in simple cells (40-300%) than in complex cells (20
      120%), and in simple cells was strongly modulated in time. Conductance was
      invariably maximal for stimuli of the preferred orientation. Thus conductance
      changes contribute to a gain control mechanism, but the strength of this gain
      control does not depend uniquely on contrast. By assuming that the conductance
      changes are entirely synaptic, we further derived the excitatory and inhibitory
      synaptic conductances underlying the visual responses. In simple cells, these
      conductances were often arranged in push-pull: excitation increased when
      inhibition decreased and vice versa. Excitation and inhibition had similar
      preferred orientations and did not appear to differ in tuning width, suggesting
      that the intracortical synaptic inputs to simple cells of cat V1 originate from
      cells with similar orientation tuning. This finding is at odds with models where
      orientation tuning in simple cells is achieved by inhibition at off-optimal
      orientations or sharpened by inhibition that is more broadly tuned than
      excitation.

PMID- 10938317
TI  - pH Sensitivity of non-synaptic field bursts in the dentate gyrus.
AB  - Under conditions of low [Ca(2+)](o) and high [K(+)](o), the rat dentate granule
      cell layer in vitro develops recurrent spontaneous prolonged field bursts that
      resemble an in vivo phenomenon called maximal dentate activation. To understand
      how pH changes in vivo might affect this phenomenon, the slices were exposed to
      different extracellular pH environments in vitro. The field bursts were highly
      sensitive to extracellular pH over the range 7.0-7.6 and were suppressed at low
      pH and enhanced at high pH. Granule cell resting membrane potential, action
      potentials, and postsynaptic potentials were not significantly altered by pH
      changes within the range that suppressed the bursts. The pH sensitivity of the
      bursts was not altered by pharmacologic blockade of N-methyl-D-aspartate (NMDA),
      non-NMDA, and GABA(A) receptors at concentrations of these agents sufficient to
      eliminate both spontaneous and evoked synaptic potentials. Gap junction patency
      is known to be sensitive to pH, and agents that block gap junctions, including
      octanol, oleamide, and carbenoxolone, blocked the prolonged field bursts in a
      manner similar to low pH. Perfusion with gap junction blockers or acidic pH
      suppressed field bursts but did not block spontaneous firing of single and
      multiple units, including burst firing. These data suggest that the pH
      sensitivity of seizures and epileptiform phenomena in vivo may be mediated in
      large part through mechanisms other than suppression of NMDA-mediated or other
      excitatory synaptic transmission. Alterations in electrotonic coupling via gap
      junctions, affecting field synchronization, may be one such process.

PMID- 10938318
TI  - Auditory thalamus neurons during sleep: changes in frequency selectivity,
      threshold, and receptive field size.
AB  - The present study describes how the frequency receptive fields (RF) of auditory
      thalamus neurons are modified when the state of vigilance of an unanesthetized
      animal naturally fluctuates among wakefulness (W), slow-wave sleep (SWS), and
      paradoxical sleep (PS). Systematic quantification of several RF parameters
      including strength of the evoked responses, response latency, acoustic threshold,
      shape of rate-level function, frequency selectivity, and RF size-was performed
      while undrugged, restrained guinea pigs presented spontaneous alternances of W,
      SWS, and PS. Data are from 102 cells recorded during W and SWS and from 53 cells
      recorded during W, SWS, and PS. During SWS, thalamic cells behaved as an
      homogeneous population: as compared with W, most of them (97/102 cells) exhibited
      decreased evoked spike rates. The frequency selectivity was enhanced and the RF
      size was reduced. In contrast during PS, two populations of cells were
      identified: one (32/53 cells) showed the same pattern of changes as during SWS,
      whereas the other (21/53 cells) expressed values of evoked spike rates and RF
      properties that did not significantly differ from those in W. These two
      populations were equally distributed in the different anatomical divisions of the
      auditory thalamus. Last, during both SWS and PS, the responses latency was longer
      and the acoustic threshold was higher than in W but the proportion of monotonic
      versus nonmonotonic rate-level functions was unchanged. During both SWS and PS,
      no relationship was found between the changes in burst percentage and the changes
      of the RF properties. These results point out the dual aspect of sensory
      processing during sleep. On the one hand, they show that the auditory messages
      sent by thalamic cells to cortical neurons are reduced both in terms of firing
      rate at a given frequency and in terms of frequency range. On the other hand, the
      fact that the frequency selectivity and the rate-level function are preserved
      suggests that the messages sent to cortical cells are not deprived of informative
      content, and that the analysis of complex acoustic sounds should remain possible.
      This can explain why, although attenuated, reactivity to biologically relevant
      stimuli is possible during sleep.

PMID- 10938319
TI  - Characteristics of the pupillary light reflex in the macaque monkey: metrics.
AB  - To investigate whether the simian light reflex is a reasonable model for the
      human light reflex, we elicited pupillary responses in three behaving rhesus
      macaques. We measured the change in pupillary area in response to brief (100 ms),
      intermediate (1 s), and long (3-5 s) light flashes delivered by light-emitting
      diodes while the monkey fixated a stationary target. Individual responses in the
      same monkey to either 100-ms or 1-s stimuli of the same light intensity were
      quite variable. Nevertheless, in response to the 100-ms stimulus, average
      pupillary constriction and peak constriction velocity increased and latency
      decreased linearly with the log of stimulus luminance. The minimum average
      constriction latency across monkeys for the brightest flash was 136 ms. A linear
      decrease of constriction latency with stimulus luminance also occurs in humans,
      but their latencies are approximately 70 ms longer. In addition, peak
      constriction velocity was highly correlated with the decrease in pupillary area.
      Dilation metrics were not as well related to stimulus luminance as were
      constriction metrics. The latency from flash offset to the onset of dilation was
      relatively constant, averaging approximately 480 ms. Peak dilation velocity was
      also correlated, but less well, with the increase in pupillary area. Constriction
      generally was greater and of longer duration for 1-s light pulses than for 100-ms
      pulses of equal luminance. The initial time courses of the responses to the two
      stimuli of different durations were identical until approximately 150 ms after
      response onset. Human pupillary responses for long and short flashes also have
      identical initial time courses. For very long (3-5 s) and very bright constant
      luminance stimuli, the simian pupil underwent oscillations at frequencies of 0.9
      1.6 Hz. Similar oscillations, called hippus, occur in the human pupillary light
      reflex. Like humans, the monkeys also exhibited consensual and binocular
      pupillary responses. Except for response latency, the pupillary responses in the
      two primate species are otherwise quite similar. Therefore any knowledge we gain
      about the neuronal substrate of the simian light reflex can be expected to have
      considerable relevance when extrapolated to humans.

PMID- 10938320
TI  - Characteristics of the pupillary light reflex in the macaque monkey: discharge
      patterns of pretectal neurons.
AB  - Anatomical and physiological data have implicated the pretectal olivary nucleus
      (PON) as the midbrain relay for the pupillary light reflex in a variety of
      species. To determine the nature of the discharge of pretectal light reflex relay
      neurons, we recorded their activity in monkeys that were fixating a stationary
      spot while a full-field random-dot stimulus was flashed on for 1 s. Based on
      their discharge patterns, neurons in or near the PON came in two varieties. The
      most prevalent neuron discharged a burst of spikes 56 ms (on average) after the
      light came on followed by a sustained rate for the duration of the stimulus
      (burst-sustained neurons). When the light went off, nearly all neurons (33/34)
      ceased firing, and then all the neurons with a resting response in the dark (n =
      15) resumed firing. Both the firing rate within the burst and the sustained
      discharge rate increased with log light intensity and the latency of the burst
      decreased. The burst and cessation of firing were better aligned with the
      stimulus occurrence than with the onset of pupillary constriction or dilation.
      Taken together, these data suggest that burst-sustained neurons respond to the
      visual stimulus eliciting the pupillary change rather than dictating the metrics
      of the subsequent pupillary response. Electrical stimulation at the site of four
      of five burst-sustained neurons elicited pupillary constriction at low stimulus
      strengths after a latency of approximately 100 ms. When the electrode was moved
      250 microm away from the burst-sustained neuron, the elicited response
      disappeared. Reconstructions of the locations of burst-sustained luminance
      neurons place them in the PON or its immediate vicinity. We suggest that PON
      burst-sustained neurons constitute the pretectal relay for the pupillary light
      reflex. A minority of our recorded pretectal neurons discharged a burst of spikes
      at both light onset and light offset. For most of these transient neurons,
      neither the burst rate nor the interburst rate was significantly related to light
      intensity. We conclude that these neurons are not involved in the light reflex
      but subserve some other pretectal function.

PMID- 10938321
TI  - Multistability in recurrent neural loops arising from delay.
AB  - The dynamics of a recurrent inhibitory neural loop composed of a periodically
      spiking Aplysia motoneuron reciprocally connected to a computer are investigated
      as a function of the time delay, tau, for propagation around the loop. It is
      shown that for certain choices of tau, multiple qualitatively different neural
      spike trains co-exist. A mathematical model is constructed for the dynamics of
      this pulsed-coupled recurrent loop in which all parameters are readily measured
      experimentally: the phase resetting curve of the neuron for a given simulated
      postsynaptic current and tau. For choices of the parameters for which multiple
      spiking patterns co-exist in the experimental paradigm, the model exhibits
      multistability. Numerical simulations suggest that qualitatively similar results
      will occur if the motoneuron is replaced by several other types of neurons and
      that once tau becomes sufficiently long, multistability will be the dominant form
      of dynamical behavior. These observations suggest that great care must be taken
      in determining the etiology of qualitative changes in neural spiking patterns,
      particularly when propagation times around polysynaptic loops are long.

PMID- 10938322
TI  - Prior information in motor and premotor cortex: activity during the delay period
      and effect on pre-movement activity.
AB  - In instructed-delay (ID) tasks, instructional cues provide prior information
      about the nature of a movement to execute after a delay. Neuronal responses in
      dorsal premotor cortex (PMd) during the instructed-delay period (IDP) between the
      CUE and subsequent GO signals are presumed to reflect early planning stages
      initiated by the prior information. In contrast, in multiple-choice reaction-time
      (RT) tasks, all motor planning and execution processes must occur after the GO
      signal. These assumptions predict that neuronal planning correlates recorded
      during the IDP of ID trials should share common features with early post-GO
      activity in RT trials, and that those response components need not be
      recapitulated after the GO signal of ID trials. These two predictions were tested
      by comparing activity recorded in RT and ID tasks from 503 neurons in PMd and
      caudal (MIc) and rostral (MIr) primary motor cortex. The incidence and strength
      of directionally tuned IDP activity declined progressively from PMd to MIc. The
      directional tuning of activity during the IDP of ID trials was more similar to
      that in the reaction-time epoch (RTE) of RT trials than after movement onset,
      especially in PMd. A modulation of post-GO activity was often observed between RT
      and ID trials and was confined mainly to the RTE. This effect was also most
      prominent in PMd. The most common change was a reduction in intensity of short
      latency phasic responses to the GO signal between RT and ID trials, especially in
      PMd cells with a short-latency phasic response to CUE signals. However, the
      largest group of cells in each area showed no large change in peak RTE activity
      between RT and ID trials, whether they were active in the IDP or not. Since early
      phasic CUE-related responses are least likely to be recapitulated after the GO
      signal in ID trials, they may be a neuronal correlate of an early planning stage
      such as response selection. Tonic IDP responses, which are not as strongly
      associated with a post-GO reduction in activity, may be related to other aspects
      of motor planning and preparation. Finally, a major component of the movement
      related activity in both MI and PMd is not susceptible to modification by prior
      information and is indivisibly coupled temporally to movement execution.

PMID- 10938323
TI  - GABA(B) receptors are the first target of released GABA at lamina I inhibitory
      synapses in the adult rat spinal cord.
AB  - We have previously provided functional evidence that glycine and GABA are
      contained in the same synaptic vesicles and coreleased at the same synapses in
      lamina I of the rat spinal dorsal horn. However, whereas both glycine receptors
      (GlyRs) and GABA(A) receptors (GABA(A)Rs) are expressed on the postsynaptic
      target, under certain conditions inhibitory events appeared to be mediated by
      GlyRs only. We therefore wanted to test whether GABA(B) receptors could be
      activated in conditions where GABA released was insufficient to activate
      GABA(A)Rs. Focal stimulation in the vicinity of visually identified lamina I
      neurons elicited monosynaptic IPSCs in the presence of ionotropic glutamate
      receptor antagonists. Pairs of stimuli were given at different interstimulus
      intervals (ISI), ranging from 25 ms to 1 s to study the depression of the second
      of evoked IPSCs (paired pulse depression; PPD). Maximal PPD of IPSCs was 60 +/-
      14% (SE) (of the conditioning pulse amplitude), at ISI between 150 and 200 ms.
      PPD was observed with IPSCs evoked at stimulus intensities where they had no
      GABA(A)R component. PPD of small evoked IPSCs was not affected by the GABA(A)R
      antagonist bicuculline but significantly attenuated by 10-30 microM CGP52432, a
      specific GABA(B) receptor antagonist. These data indicate that, under conditions
      where GABA released is insufficient to affect postsynaptic GABA(A)Rs at lamina I
      inhibitory synapses, significant activation of presynaptic GABA(B) receptors can
      occur.

PMID- 10938324
TI  - Shapes and level tolerances of frequency tuning curves in primary auditory
      cortex: quantitative measures and population codes.
AB  - The shape and level tolerance of the excitatory frequency/intensity tuning curves
      (eFTCs) of 160 cat primary auditory cortical (A1) neurons were investigated.
      Overall, A1 cells were characterized by tremendous variety in eFTC shapes and
      symmetries; eFTCs were U-shaped ( approximately 20%), V-shaped ( approximately
      20%), lower-tail-upper-sharp ( approximately 15%), upper-tail-lower-sharp (<2%),
      slant-lower ( approximately 10%), slant-upper (<3%), multipeaked ( approximately
      10%), and circumscribed ( approximately 20%). Quantitative analysis suggests that
      eFTC are best thought of as forming a continuum of shapes, rather than falling
      into discrete categories. A1 eFTCs tended to be more level tolerant than eFTCs
      from earlier stations in the ascending auditory system as inferred from other
      studies. While individual peaks of multipeaked eFTCs were similar to single
      peaked eFTCs, the overall eFTC of multipeaked neurons (spanning the range of all
      peaks) tended to have high-frequency tails. Measurements of shape and symmetry
      indicate that A1 eFTCs, on average, tended to have greater area on the low
      frequency side of characteristic frequency (CF) than on the high-frequency side.
      A1 cells showed a relationship between CF and the inverse slope of low-frequency
      edges of eFTCs, but not for high-frequency edges. These data demonstrate that
      frequency tuning, particularly along the eFTC low-frequency border, sharpens
      along the lemniscal pathway to A1. The results are consistent with studies in
      mustached bats (Suga 1997) and support the idea that spectral decomposition along
      the ascending lemniscal pathway up to A1 is a general organizing principle of
      mammalian auditory systems. Altogether, these data suggest that A1 neurons' eFTCs
      are shaped by complex patterns of inhibition and excitation accumulating along
      the auditory pathways, implying that central rather than peripheral filtering
      properties are responsible for certain psychophysical phenomena.

PMID- 10938325
TI  - Context estimation for sensorimotor control.
AB  - Human motor behavior is remarkably accurate and appropriate even though the
      properties of our own bodies as well as the objects we interact with vary over
      time. To adjust appropriately, the motor system has to estimate the context, that
      is the properties of objects in the world and the prevailing environmental
      conditions. Here we show that to determine the current context the CNS uses
      information from both prior knowledge of how the context might evolve over time
      and from the comparison of predicted and actual sensory feedback. We show that
      these two sources of information may be modeled within the CNS and combined to
      derive an accurate estimate of the context which adjusts motor command selection.
      This provides a novel probabilistic framework for sensorimotor control.

PMID- 10938326
TI  - Anatomy and discharge properties of pre-motor neurons in the goldfish medulla
      that have eye-position signals during fixations.
AB  - Previous work in goldfish has suggested that the oculomotor velocity-to-position
      neural integrator for horizontal eye movements may be confined bilaterally to a
      distinct group of medullary neurons that show an eye-position signal. To
      establish this localization, the anatomy and discharge properties of these
      position neurons were characterized with single-cell Neurobiotin labeling and
      extracellular recording in awake goldfish while monitoring eye movements with the
      scleral search-coil method. All labeled somata (n = 9) were identified within a
      region of a medially located column of the inferior reticular formation that was
      approximately 350 microm in length, approximately 250 microm in depth, and
      approximately 125 microm in width. The dendrites of position neurons arborized
      over a wide extent of the ventral half of the medulla with especially heavy
      ramification in the initial 500 microm rostral of cell somata (n = 9). The axons
      either followed a well-defined ventral pathway toward the ipsilateral abducens (n
      = 4) or crossed the midline (n = 2) and projected toward the contralateral group
      of position neurons and the contralateral abducens. A mapping of the somatic
      region using extracellular single unit recording revealed that position neurons
      (n > 120) were the dominant eye-movement-related cell type in this area. Position
      neurons did not discharge below a threshold value of horizontal fixation position
      of the ipsilateral eye. Above this threshold, firing rates increased linearly
      with increasing temporal position [mean position sensitivity = 2.8 (spikes/s)/
      degrees, n = 44]. For a given fixation position, average rates of firing were
      higher after a temporal saccade than a nasal one (n = 19/19); the magnitude of
      this hysteresis increased with increasing position sensitivity. Transitions in
      firing rate accompanying temporal saccades were overshooting (n = 43/44),
      beginning, on average, 17.2 ms before saccade onset (n = 17). Peak firing rate
      change accompanying temporal saccades was correlated with eye velocity (n =
      36/41). The anatomical findings demonstrate that goldfish medullary position
      neurons have somata that are isolated from other parts of the oculomotor system,
      have dendritic fields overlapping with axonal terminations of neurons with
      velocity signals, and have axons that are capable of relaying commands to the
      abducens. The physiological findings demonstrate that the signals carried by
      position neurons could be used by motoneurons to set the fixation position of the
      eye. These results are consistent with a role for position neurons as elements of
      the velocity-to-position neural integrator for horizontal eye movements.

PMID- 10938327
TI  - Cornea-responsive medullary dorsal horn neurons: modulation by local opioids and
      projections to thalamus and brain stem.
AB  - Previously, it was determined that microinjection of morphine into the caudal
      portion of subnucleus caudalis mimicked the facilitatory effects of intravenous
      morphine on cornea-responsive neurons recorded at the subnucleus
      interpolaris/caudalis (Vi/Vc) transition region. The aim of the present study was
      to determine the opioid receptor subtype(s) that mediate modulation of corneal
      units and to determine whether opioid drugs affected unique classes of units.
      Pulses of CO(2) gas applied to the cornea were used to excite neurons at the
      Vi/Vc ("rostral" neurons) and the caudalis/upper cervical spinal cord transition
      region (Vc/C1, "caudal" neurons) in barbiturate-anesthetized male rats.
      Microinjection of morphine sulfate (2.9-4.8 nmol) or the selective mu receptor
      agonist D-Ala, N-Me-Phe, Gly-ol-enkephalin (DAMGO; 1.8-15.0 pmol) into the caudal
      transition region enhanced the response in 7 of 27 (26%) rostral units to CO(2)
      pulses and depressed that of 10 units (37%). Microinjection of a selective delta
      ([D-Pen(2,5)] (DPDPE); 24-30 pmol) or kappa receptor agonist (U50488; 1.8-30.0
      pmol) into the caudal transition region did not affect the CO(2)-evoked responses
      of rostral units. Caudal units were inhibited by local DAMGO or DPDPE but were
      not affected by U50,488H. The effects of DAMGO and DPDPE were reversed by
      naloxone (0.2 mg/kg iv). Intravenous morphine altered the CO(2)-evoked activity
      in a direction opposite to that of local DAMGO in 3 of 15 units, in the same
      direction as local DAMGO but with greater magnitude in 4 units, and in the same
      direction with equal magnitude as local DAMGO in 8 units. CO(2)-responsive
      rostral and caudal units projected to either the thalamic posterior nucleus/zona
      incerta region (PO/ZI) or the superior salivatory/facial nucleus region
      (SSN/VII). However, rostral units not responsive to CO(2) pulses projected only
      to SSN/VII and caudal units not responsive to CO(2) projected only to PO/ZI. It
      was concluded that the circuitry for opioid analgesia in corneal pain involves
      multiple sites of action: inhibition of neurons at the caudal transition region,
      by intersubnuclear connections to modulate rostral units, and by supraspinal
      sites. Local administration of opioid agonists modulated all classes of corneal
      units. Corneal stimulus modality was predictive of efferent projection status for
      rostral and caudal units to sensory thalamus and reflex areas of the brain stem.

PMID- 10938328
TI  - ROMK1 (Kir1.1) causes apoptosis and chronic silencing of hippocampal neurons.
AB  - Lentiviral vectors were constructed to express the weakly rectifying kidney K(+)
      channel ROMK1 (Kir1.1), either fused to enhanced green fluorescent protein (EGFP)
      or as a bicistronic message (ROMK1-CITE-EGFP). The channel was stably expressed
      in cultured rat hippocampal neurons. Infected cells were maintained for 2-4 wk
      without decrease in expression level or evidence of viral toxicity, although 15.4
      mM external KCl was required to prevent apoptosis of neurons expressing
      functional ROMK1. No other trophic agents tested could prevent cell death, which
      was probably caused by K(+) loss. This cell death did not occur in glia, which
      were able to support ROMK1 expression indefinitely. Functional ROMK1, quantified
      as the nonnative inward current at -144 mV in 5.4 mM external K(+) blockable by
      500 microM Ba(2+), ranged from 1 to 40 pA/pF. Infected neurons exhibited a Ba(2+)
      induced depolarization of 7 +/- 2 mV relative to matched EGFP-infected controls,
      as well as a 30% decrease in input resistance and a shift in action potential
      threshold of 2.6 +/- 0.5 mV. This led to a shift in the relation between injected
      current and firing frequency, without changes in spike shape, size, or timing.
      This shift, which quantifies silencing as a function of ROMK1 expression, was
      predicted from Hodgkin-Huxley models. No cellular compensatory mechanisms in
      response to expression of ROMK1 were identified, making ROMK1 potentially useful
      for transgenic studies of silencing and neurodegeneration, although its lethality
      in normal K(+) has implications for the use of K(+) channels in gene therapy.

PMID- 10938329
TI  - Spiking-bursting activity in the thalamic reticular nucleus initiates sequences
      of spindle oscillations in thalamic networks.
AB  - Recent intracellular and local field potential recordings from thalamic reticular
      (RE) neurons in vivo as well as computational modeling of the isolated RE nucleus
      suggest that, at relatively hyperpolarized levels of membrane potentials, the
      inhibitory postsynaptic potentials (IPSPs) between RE cells can be reversed and
      gamma-aminobutyric acid-A (GABA(A)) -mediated depolarization can generate
      persistent spatio-temporal patterns in the RE nucleus. Here we investigate how
      this activity affects the spatio-temporal properties of spindle oscillations with
      computer models of interacting RE and thalamocortical (TC) cells. In a one
      dimensional network of RE and TC cells, sequences of spindle oscillations
      alternated with localized patterns of spike-burst activity propagating inside the
      RE network. New sequences of spindle oscillations were initiated after removal of
      I(h)-mediated depolarization of the TC cells. The length of the interspindle
      lulls depended on the intrinsic and synaptic properties of RE and TC cells and
      was in the range of 3-20 s. In a two-dimensional model, GABA(A)-mediated 2-3 Hz
      oscillations persisted in the RE nucleus during interspindle lulls and initiated
      spindle sequences at many foci within the RE-TC network simultaneously. This
      model predicts that the intrinsic properties of the reticular thalamus may
      contribute to the synchrony of spindle oscillations observed in vivo.

PMID- 10938330
TI  - Reflex responses induced by tooth unloading.
AB  - The reflex response of the masseter muscle to the rapid unloading of a single
      maxillary incisor tooth was studied. Unloading of a static force of 2 N in the
      horizontal direction resulted in a short-latency excitation, inhibition, and long
      latency excitation of masseter muscle activity occurring at latencies of
      approximately 13, 20, and 40 ms, respectively, with a corresponding change in
      bite force occurring slightly later in each case. Following the blocking of
      periodontal input by the injection of local anesthetic around the stimulated
      tooth, inhibitory responses were abolished. Therefore, it is concluded that the
      observed masseteric inhibition was caused by the unloading of periodontal
      mechanoreceptors and thus that these receptors may contribute to the jaw
      unloading reflex.

PMID- 10938331
TI  - Spindle-like thalamocortical synchronization in a rat brain slice preparation.
AB  - We obtained rat brain slices (550-650 microm) that contained part of the
      frontoparietal cortex along with a portion of the thalamic ventrobasal complex
      (VB) and of the reticular nucleus (RTN). Maintained reciprocal thalamocortical
      connectivity was demonstrated by VB stimulation, which elicited orthodromic and
      antidromic responses in the cortex, along with re-entry of thalamocortical firing
      originating in VB neurons excited by cortical output activity. In addition,
      orthodromic responses were recorded in VB and RTN following stimuli delivered in
      the cortex. Spontaneous and stimulus-induced coherent rhythmic oscillations
      (duration = 0.4-3.5 s; frequency = 9-16 Hz) occurred in cortex, VB, and RTN
      during application of medium containing low concentrations of the K(+) channel
      blocker 4-aminopyridine (0.5-1 microM). This activity, which resembled
      electroencephalograph (EEG) spindles recorded in vivo, disappeared in both cortex
      and thalamus during application of the excitatory amino acid receptor antagonist
      kynurenic acid in VB (n = 6). By contrast, cortical application of kynurenic acid
      (n = 4) abolished spindle-like oscillations at this site, but not those recorded
      in VB, where their frequency was higher than under control conditions. Our
      findings demonstrate the preservation of reciprocally interconnected cortical and
      thalamic neuron networks that generate thalamocortical spindle-like oscillations
      in an in vitro rat brain slice. As shown in intact animals, these oscillations
      originate in the thalamus where they are presumably caused by interactions
      between RTN and VB neurons. We propose that this preparation may help to analyze
      thalamocortical synchronization and to understand the physiopathogenesis of
      absence attacks.

PMID- 10938332
TI  - Population and unit synchrony of fast rhythms in expiratory recurrent laryngeal
      discharges.
AB  - In a decerebrate, vagotomized, gallamine-paralyzed cat that had a prominent
      bilaterally coherent fast rhythm (50 Hz) in expiratory (E) recurrent laryngeal
      (RL) nerve discharges, recordings were taken of the firing of nine RL E fibers.
      This rhythm (called E high-frequency oscillation or EHFO) was seen as a sharp
      peak in all unit autospectra, all unit-nerve coherence spectra (value range 0.39
      0. 91), and all unit-unit coherence spectra (value range 0.27-0.85). In addition,
      8/9 units had a sharp autospectral peak in a lower frequency range (19-35 Hz)
      called E medium-frequency oscillation (EMFO), but there was no coherence at this
      frequency between signal pairs (unit-unit, unit-nerve, nerve-nerve). The MFOs are
      specific for each unit and are considered to arise from asynchronous inputs and
      membrane properties. The HFOs are considered to arise from widespread network
      interactions that produce a common (correlated) rhythm in virtually all neurons
      of the RL E network. These phenomena suggest the use of the RL E network as a
      model system for analyzing rhythmic neural interactions.

PMID- 10938333
TI  - Electrical stimulation of the frontal eye field in a monkey produces combined eye
      and head movements.
AB  - The frontal eye field (FEF), an area in the primate frontal lobe, has long been
      considered important for the production of eye movements. Past studies have
      evoked saccade-like movements from the FEF using electrical stimulation in
      animals that were not allowed to move their heads. Using electrical stimulation
      in two monkeys that were free to move their heads, we have found that the FEF
      produces gaze shifts that are composed of both eye and head movements. Repeated
      stimulation at a site evoked gaze shifts of roughly constant amplitude. However,
      that gaze shift could be accomplished with varied amounts of head and eye
      movements, depending on their (head and eye) respective starting positions. This
      evidence suggests that the FEF controls visually orienting movements using both
      eye and head rotations rather than just shifting the eyes as previously thought.

PMID- 10938334
TI  - Vestibular influence on human auditory space perception.
AB  - We investigated the effect of vestibular stimulation on the lateralization of
      dichotic sound by cold-water irrigation of the external auditory canal in human
      subjects. Subjects adjusted the interaural level difference of the auditory
      stimulus to the subjective median plane of the head. In those subjects in whom
      dizziness and nystagmus indicated sufficient vestibular stimulation, these
      adjustments were significantly shifted toward the cooled ear compared with the
      control condition (irrigation with water at body temperature); i.e., vestibular
      stimulation induced a shift of the sound image toward the nonstimulated side. The
      mean magnitude of the shift was 7.3 dB immediately after vestibular stimulation
      and decreased to 2.5 dB after 5 min. As shown by an additional control
      experiment, this effect cannot be attributed to a unilateral hearing loss induced
      by cooling of the auditory periphery. The results indicate the involvement of
      vestibular afferent information in the perception of sound location during
      movements of the head and/or the whole body. We thus hypothesize that vestibular
      information is used by central-nervous mechanisms generating a world-centered
      representation of auditory space.

PMID- 10938335
TI  - Phase-dependent filtering of sensory information in the oscillatory olfactory
      center of a terrestrial mollusk.
AB  - With electrophysiological techniques, we found phase-dependent modification of
      the efficacy of signal transmission in the procerebrum (PC), the oscillatory
      olfactory center, of the terrestrial mollusk Limax marginatus and elucidated its
      neuronal mechanism. Previous studies have indicated that about 10(5) PC neurons
      can be classified into only two types: bursting (B) neurons and nonbursting (NB)
      neurons, and both types of neurons have ongoing and phase-locked periodic
      oscillation of their membrane potentials. On olfactory nerve stimulation,
      excitatory postsynaptic potentials (EPSPs) were evoked with a constant latency in
      NB neurons, while EPSPs with a variable latency were evoked in B neurons. These
      findings suggest a monosynaptic connection from the olfactory nerve to NB
      neurons, but a polysynaptic connection between the olfactory nerve and B neurons.
      This polysynaptic transmission is most likely mediated by NB neurons because the
      olfactory nerve makes synaptic connection only with NB neurons in the PC. The
      latency of the evoked EPSPs in B neurons depended on the phase of the PC
      oscillatory activity, presumably because of the oscillation of the intervening NB
      neurons. These results suggest that the efficacy of olfactory nerve-B neuron
      polysynaptic transmission is regulated by the activity level of the phasically
      oscillating NB neurons. Thus, the intrinsic oscillation in the PC can serve as a
      filter for olfactory information conveyed from the olfactory nerve as a train of
      neuronal spikes. This filtering system may also produce a phase-dependent
      modification by the olfactory input of the PC oscillation frequency.

PMID- 10938336
TI  - Important role of reverse Na(+)-Ca(2+) exchange in spinal cord white matter
      injury at physiological temperature.
AB  - Spinal cord injury is a devastating condition in which most of the clinical
      disability results from dysfunction of white matter tracts. Excessive cellular
      Ca(2+) accumulation is a common phenomenon after anoxia/ischemia or mechanical
      trauma to white matter, leading to irreversible injury because of overactivation
      of multiple Ca(2+)-dependent biochemical pathways. In the present study, we
      examined the role of Na(+)-Ca(2+) exchange, a ubiquitous Ca(2+) transport
      mechanism, in anoxic and traumatic injury to rat spinal dorsal columns in vitro.
      Excised tissue was maintained in a recording chamber at 37 degrees C and injured
      by exposure to an anoxic atmosphere for 60 min or locally compressed with a force
      of 2 g for 15 s. Mean compound action potential amplitude recovered to
      approximately 25% of control after anoxia and to approximately 30% after trauma.
      Inhibitors of Na(+)-Ca(2+) exchange (50 microM bepridil or 10 microM KB-R7943)
      improved functional recovery to approximately 60% after anoxia and approximately
      70% after traumatic compression. These inhibitors also prevented the increase in
      calpain-mediated spectrin breakdown products induced by anoxia. We conclude that,
      at physiological temperature, reverse Na(+)-Ca(2+) exchange plays an important
      role in cellular Ca(2+) overload and irreversible damage after anoxic and
      traumatic injury to dorsal column white matter tracts.

PMID- 10938337
TI  - Age-dependent changes in axonal branching of single locus coeruleus neurons
      projecting to two different terminal fields.
AB  - Age-dependent changes in the axonal branching patterns of single locus coeruleus
      neurons, which innervate both the frontal cortex and hippocampus dentate gyrus,
      have been studied in male F344 rats. We used an electrophysiological approach
      involving antidromic activation to differentiate single from multi-threshold
      locus coeruleus neurons in each terminal field with age (7-27 mo of age). Most of
      these neurons have a single threshold in the young rats, whereas in the older
      brains, the neurons have multi-threshold responses. This implies an increased
      amount of axonal branching in the older brains. The time course of the increase
      differs in the two terminal fields, suggesting that the degree of plasticity or
      age-dependent increase in branching can differ across terminal fields.

PMID- 10938338
TI  - The genetically modified organism conflict.

PMID- 10938339
TI  - High throughput cellular localization of specific plant mRNAs by liquid-phase in
      situ reverse transcription-polymerase chain reaction of tissue sections.
AB  - Advances in high throughput DNA sequencing and bioinformatic gene discovery far
      outpace our ability to analyze gene function, necessitating development of more
      efficient means to examine expression at the cellular level. Here we present a
      polymerase chain reaction-based method to detect mRNA species in situ in which
      essentially all of the steps are carried out in liquid phase in a 96-well
      microtiter tray and only the final signal detection is performed on a microscope
      slide. We demonstrate the sensitivity of the method by the cellular localization
      of mRNA for the Tkn2 transcription factor in a wide variety of plant tissues, and
      its selectivity in discriminating a single gene family member by the in situ
      localization of rbcs3 transcripts. Furthermore, we demonstrate the utility of the
      in-well in situ method in detecting FDL and IFL1 transcripts in Arabidopsis
      sections, thus establishing the method as a tool to determine spatial expression
      pattern of sequences obtained from genomic sequencing projects. Being amenable to
      robotic processing, in-well in situ reverse transcription-polymerase chain
      reaction permits a great enhancement in the number of tissue samples that can be
      processed. Consequently, this method may become a powerful tool for functional
      genomics studies, permitting the cellular site of transcription of large numbers
      of sequences obtained from databases to be rapidly established.

PMID- 10938340
TI  - Organelle fission. Crossing the evolutionary divide.

PMID- 10938341
TI  - Vesicle-mediated solute transport between the vacuole and the plasma membrane.

PMID- 10938342
TI  - Endoplasmic reticulum-derived compartments function in storage and as mediators
      of vacuolar remodeling via a new type of organelle, precursor protease vesicles.

PMID- 10938343
TI  - A germination-specific endo-beta-mannanase gene is expressed in the micropylar
      endosperm cap of tomato seeds.
AB  - Endo-beta-mannanase (EC 3.2.1.78) is involved in hydrolysis of the mannan-rich
      cell walls of the tomato (Lycopersicon esculentum Mill.) endosperm during
      germination and post-germinative seedling growth. Different electrophoretic
      isoforms of endo-beta-mannanase are expressed sequentially in different parts of
      the endosperm, initially in the micropylar endosperm cap covering the radicle tip
      and subsequently in the remaining lateral endosperm surrounding the rest of the
      embryo. We have isolated a cDNA from imbibed tomato seeds (LeMAN2) that shares
      77% deduced amino acid sequence similarity with a post-germinative tomato
      mannanase (LeMAN1). When expressed in Escherichia coli, the protein encoded by
      LeMAN2 cDNA was recognized by anti-mannanase antibody and exhibited endo-beta
      mannanase activity, confirming the identity of the gene. LeMAN2 was expressed
      exclusively in the endosperm cap tissue of tomato seeds prior to radicle
      emergence, whereas LeMAN1 was expressed only in the lateral endosperm after
      radicle emergence. LeMAN2 mRNA accumulation and mannanase activity were induced
      by gibberellin in gibberellin-deficient gib-1 mutant seeds but were not inhibited
      by abscisic acid in wild-type seeds. Distinct mannanases are involved in
      germination and post-germinative growth, with LeMAN2 being associated with
      endosperm cap weakening prior to radicle emergence, whereas LeMAN1 mobilizes
      galactomannan reserves in the lateral endosperm.

PMID- 10938344
TI  - Brassinosteroid-insensitive-1 is a ubiquitously expressed leucine-rich repeat
      receptor serine/threonine kinase.
AB  - Brassinosteroid (BR) mutants of Arabidopsis have pleiotropic phenotypes and
      provide evidence that BRs function throughout the life of the plant from seedling
      development to senescence. Screens for BR signaling mutants identified one locus,
      BRI1, which encodes a protein with homology to leucine-rich repeat receptor
      serine (Ser)/threonine (Thr) kinases. Twenty-seven alleles of this putative BR
      receptor have been isolated to date, and we present here the identification of
      the molecular lesions of 14 recessive alleles that represent five new mutations.
      BR-insensitive-1 (BRI1) is expressed at high levels in the meristem, root, shoot,
      and hypocotyl of seedlings and at lower levels later in development. Confocal
      microscopy analysis of full-length BRI1 fused to green fluorescent protein
      indicates that BRI1 is localized in the plasma membrane, and an in vitro kinase
      assay indicates that BRI1 is a functional Ser/Thr kinase. Among the bri1 mutants
      identified are mutants in the kinase domain, and we demonstrate that one of these
      mutations severely impairs BRI1 kinase activity. Therefore, we conclude that BRI1
      is a ubiquitously expressed leucine-rich repeat receptor that plays a role in BR
      signaling through Ser/Thr phosphorylation.

PMID- 10938346
TI  - Specific lipoxygenase isoforms accumulate in distinct regions of soybean pod
      walls and mark a unique cell layer.
AB  - Developing seeds constitute a strong sink for the plant and rely on the turnover
      and mobilization of carbon and nitrogen assimilates to supply the nutrients
      needed for their maturation. In large part these nutrients emanate from the
      vegetative organs including leaves and pod walls. Vegetative lipoxygenases (VLXs)
      accumulate in the paraveinal mesophyll cell layer of soybean (Glycine max L.)
      leaves where individual isoforms are proposed to play a role(s) as active enzymes
      or as transient storage proteins. VLXs also are prominent proteins in soybean pod
      walls, representing approximately 12% of the total soluble protein. Examining the
      temporal, tissue, and subcellular patterns of individual VLX isoform accumulation
      and of lipoxygenase activity through pod wall development indicates that VLXD is
      the principal VLX isoform playing a role in storage in this organ. The major
      accumulation of VLXD occurs just prior to seed fill within the endocarp middle
      zone, and protein extracted from this region shows relatively low levels of
      lipoxygenase activity, suggesting the middle zone may act as a storage tissue.
      Three other VLX isoforms, VLXA, VLXB, and VLXC colocalize to the cytoplasm of a
      single discrete cell layer in the mesocarp. Thus, the patterns of VLX cellular
      and subcellular localization in pod walls suggest independent functions for these
      different isoforms while also serving as specific markers for a novel cell layer
      in the pod wall.

PMID- 10938345
TI  - Farnesol-induced cell death and stimulation of 3-hydroxy-3-methylglutaryl
      coenzyme A reductase activity in tobacco cv bright yellow-2 cells.
AB  - Growth inhibition of tobacco (Nicotiana tabacum L. cv Bright Yellow-2) cells by
      mevinolin, a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase (HMGR) could be partially overcome by the addition of farnesol.
      However, farnesol alone inhibited cell division and growth as measured by
      determination of fresh weight increase. When 7-d-old tobacco cv Bright Yellow-2
      cells were diluted 40-fold into fresh culture, the cells exhibited a dose
      dependent sensitivity to farnesol, with 25 microM sufficient to cause 100% cell
      death, as measured by different staining techniques, cytometry, and monitoring of
      fragmentation of genomic DNA. Cells were less sensitive to the effects of
      farnesol when diluted only 4-fold. Farnesol was absorbed by the cells, as
      examined by [1-(3)H]farnesol uptake, with a greater relative enrichment by the
      more diluted cells. Both mevinolin and farnesol treatments stimulated apparent
      HMGR activity. The stimulation by farnesol was also reflected in corresponding
      changes in the steady-state levels of HMGR mRNA and enzyme protein with respect
      to HMGR gene expression and enzyme protein accumulation.

PMID- 10938347
TI  - The mid-pericarp cell layer in soybean pod walls is a multicellular compartment
      enriched in specific lipoxygenase isoforms.
AB  - Specific lipoxygenase isoforms immunolocalize to the cytosol of a single cell
      layer in the soybean (Glycine max L.) pod wall. The cells of this layer, termed
      the mid-pericarp layer (MPL), are larger than adjacent cells and are highly
      branched. The entire MPL appears to form an elaborate interdigitated network
      within the pod wall. A particularly striking feature of the MPL is the presence
      of extensive regions of very thin, approximately 30 nm, cell wall, which connect
      the cells of the MPL. It was demonstrated that after mechanical wounding of the
      pod wall, 40-kD fluorescein-dextran was able to move throughout the MPL. In
      addition, when pod walls are cut, an exudate flows from the MPL that is highly
      enriched in lipoxygenase isoforms (approximately 40% of the total protein). The
      MPL of soybean pod walls may represent a novel multicellular compartment involved
      in defense of leguminous plants.

PMID- 10938348
TI  - Early H(2)O(2) accumulation in mesophyll cells leads to induction of glutathione
      during the hyper-sensitive response in the barley-powdery mildew interaction.
AB  - H(2)O(2) production and changes in glutathione, catalase, and peroxidase were
      followed in whole-leaf extracts from the susceptible (AlgS [Algerian/4* (F14)
      Man.(S)]; ml-a1 allele) and resistant (AlgR [Algerian/4* (F14) Man.(R)]; Ml-a1
      allele) barley (Hordeum vulgare) isolines between 12 and 24 h after inoculation
      with powdery mildew (Blumeria graminis [DC]. Speer [syn. Erysiphe graminis DC]
      f.sp hordei Marchal). Localized papilla responses and cell death hypersensitive
      responses were not observed within the same cell. In hypersensitive response
      sites, H(2)O(2) accumulation first occurred in the mesophyll underlying the
      attacked epidermal cell. Subsequently, H(2)O(2) disappeared from the mesophyll
      and accumulated around attacked epidermal cells. In AlgR, transient glutathione
      oxidation coincided with H(2)O(2) accumulation in the mesophyll. Subsequently,
      total foliar glutathione and catalase activities transiently increased in AlgR.
      These changes, absent from AlgS, preceded inoculation-dependent increases in
      peroxidase activity that were observed in both AlgR and AlgS at 18 h. An early
      intercellular signal precedes H(2)O(2), and this elicits anti-oxidant responses
      in leaves prior to events leading to death of attacked cells.

PMID- 10938349
TI  - Calcium-mediated signaling during sandalwood somatic embryogenesis. Role for
      exogenous calcium as second messenger.
AB  - The possible involvement of Ca(2+)-mediated signaling in the induction/regulation
      of somatic embryogenesis from pro-embryogenic cells of sandalwood (Santalum
      album) has been investigated. (45)Ca(2+)-uptake studies and fura-2 fluorescence
      ratio photometry were used to measure changes in [Ca(2+)](cyt) of pro-embryogenic
      cells in response to culture conditions conducive for embryo development.
      Sandalwood pro-embryogenic cell masses (PEMs) are obtained in the callus
      proliferation medium that contains the auxin 2,4-dichlorophenoxyacetic acid.
      Subculture of PEMs into the embryo differentiation medium, which lacks 2,4
      dichlorophenoxyacetic acid and has higher osmoticum, results in a 4-fold higher
      (45)Ca(2+) incorporation into the symplast. Fura-2 ratiometric analysis
      corroboratively shows a 10- to 16-fold increase in the [Ca(2+)](cyt) of PEMs,
      increasing from a resting concentration of 30 to 50 nM to 650 to 800 nM.
      Chelation of exogenous Ca(2+) with ethyleneglycol-bis(aminoethyl ether)-N,N'
      tetraacetic acid arrests such an elevation in [Ca(2+)](cyt). Exogenous Ca(2+)
      when chelated or deprived also arrests embryo development and inhibits the
      accumulation of a sandalwood Ca(2+)-dependent protein kinase. However, such
      culture conditions do not cause cell death as the PEMs continue to proliferate to
      form larger cell clumps. Culture treatment with N-(6-aminohexyl)-5-chloro-1
      naphthalene sulfonamide reduced embryogenic frequency by 85%, indicating that
      blockage of Ca(2+)-mediated signaling pathway(s) involving sandalwood Ca(2+)
      dependent protein kinase and/or calmodulin causes the inhibition of
      embryogenesis. The observations presented are evidence to suggest a second
      messenger role for exogenous Ca(2+) during sandalwood somatic embryogenesis.

PMID- 10938350
TI  - A comparative analysis of the plant cellulose synthase (CesA) gene family.
AB  - CesA genes are believed to encode the catalytic subunit of cellulose synthase.
      Identification of nine distinct CesA cDNAs from maize (Zea mays) has allowed us
      to initiate comparative studies with homologs from Arabidopsis and other plant
      species. Mapping studies show that closely related CesA genes are not clustered
      but are found at different chromosomal locations in both Arabidopsis and maize.
      Furthermore, sequence comparisons among the CesA-deduced proteins show that these
      cluster in groups wherein orthologs are often more similar than paralogs,
      indicating that different subclasses evolved prior to the divergence of the
      monocot and dicot lineages. Studies using reverse transcriptase polymerase chain
      reaction with gene-specific primers for six of the nine maize genes indicate that
      all genes are expressed to at least some level in all of the organs examined.
      However, when expression patterns for a few selected genes from maize and
      Arabidopsis were analyzed in more detail, they were found to be expressed in
      unique cell types engaged in either primary or secondary wall synthesis. These
      studies also indicate that amino acid sequence comparisons, at least in some
      cases, may have value for prediction of such patterns of gene expression. Such
      analyses begin to provide insights useful for future genetic engineering of
      cellulose deposition, in that identification of close orthologs across species
      may prove useful for prediction of patterns of gene expression and may also aid
      in prediction of mutant combinations that may be necessary to generate severe
      phenotypes.

PMID- 10938351
TI  - Identification and characterization of three orchid MADS-box genes of the
      AP1/AGL9 subfamily during floral transition.
AB  - Gene expressions associated with in vitro floral transition in an orchid hybrid
      (Dendrobium grex Madame Thong-In) were investigated by differential display. One
      clone, orchid transitional growth related gene 7 (otg7), encoding a new MADS-box
      gene, was identified to be specifically expressed in the transitional shoot
      apical meristem (TSAM). Using this clone as a probe, three orchid MADS-box genes,
      DOMADS1, DOMADS2, and DOMADS3, were subsequently isolated from the TSAM cDNA
      library. Phylogenetic analyses show that DOMADS1 and DOMADS2 are new members of
      the AGL2 subfamily and SQUA subfamily, respectively. DOMADS3 contains the
      signature amino acids as with the members in the independent OSMADS1 subfamily
      separated from the AGL2 subfamily. All three of the DOMADS genes were expressed
      in the TSAM during floral transition and later in mature flowers. DOMADS1 RNA was
      uniformly expressed in both of the inflorescence meristem and the floral
      primordium and later localized in all of the floral organs. DOMADS2 showed a
      novel expression pattern that has not been previously characterized for any other
      MADS-box genes. DOMADS2 transcript was expressed early in the 6-week-old
      vegetative shoot apical meristem in which the obvious morphological change to
      floral development had yet to occur. It was expressed throughout the process of
      floral transition and later in the columns of mature flowers. The onset of
      DOMADS3 transcription was in the early TSAM at the stage before the
      differentiation of the first flower primordium. Later, DOMADS3 transcript was
      only detectable in the pedicel tissues. Our results suggest that the DOMADS genes
      play important roles in the process of floral transition.

PMID- 10938352
TI  - Targeted inactivation of the plastid ndhB gene in tobacco results in an enhanced
      sensitivity of photosynthesis to moderate stomatal closure.
AB  - The ndh genes encoding for the subunits of NAD(P)H dehydrogenase complex
      represent the largest family of plastid genes without a clearly defined function.
      Tobacco (Nicotiana tabacum) plastid transformants were produced in which the ndhB
      gene was inactivated by replacing it with a mutant version possessing
      translational stops in the coding region. Western-blot analysis indicated that no
      functional NAD(P)H dehydrogenase complex can be assembled in the plastid
      transformants. Chlorophyll fluorescence measurements showed that dark reduction
      of the plastoquinone pool by stromal reductants was impaired in ndhB-inactivated
      plants. Both the phenotype and photosynthetic performance of the plastid
      transformants was completely normal under favorable conditions. However, an
      enhanced growth retardation of ndhB-inactivated plants was revealed under
      humidity stress conditions causing a moderate decline in photosynthesis via
      stomatal closure. This distinctive phenotype was mimicked under normal humidity
      by spraying plants with abscisic acid. Measurements of CO(2) fixation
      demonstrated an enhanced decline in photosynthesis in the mutant plants under
      humidity stress, which could be restored to wild-type levels by elevating the
      external CO(2) concentration. These results suggest that the plastid
      NAD(P)H:plastoquinone oxidoreductase in tobacco performs a significant
      physiological role by facilitating photosynthesis at moderate CO(2) limitation.

PMID- 10938354
TI  - Lignification in transgenic poplars with extremely reduced caffeic acid O
      methyltransferase activity.
AB  - Transgenic poplars (Populus tremula x Populus alba) were obtained by introduction
      of a sense homologous transgene encoding caffeic acid O-methyltransferase (COMT)
      under the control either of the cauliflower mosaic virus double 35S promoter or
      of the eucalyptus cinnamyl alcohol dehydrogenase promoter. Although these
      constructs conferred a moderate overexpression of COMT in some lines, a
      transgenic line with the double 35S promoter was found where COMT activity in
      woody tissues was close to zero due to a gene-silencing phenomenon. For the first
      time in COMT down-regulated trees, this alteration substantially reduced lignin
      level in 6-month-old trees (17% decrease). Lignin structure was found to be
      strongly altered, with a two times higher content in condensed bonds, an almost
      complete lack of syringyl units, and the incorporation of 5-hydroxyguaiacyl units
      to the most remarkable extent reported so far. Consistent with the higher
      cellulose content and with the higher condensation degree of the lignin, the
      impact of the transformation on the kraft-pulping performances of the poplar
      trees positively affected the pulp yield (10% relative increase), but made
      lignins less amenable to industrial degradations.

PMID- 10938353
TI  - LEFPS1, a tomato farnesyl pyrophosphate gene highly expressed during early fruit
      development.
AB  - Farnesyl pyrophosphate synthase (FPS) catalyzes the synthesis of farnesyl
      pyrophosphate, a key intermediate in sterol and sesquiterpene biosynthesis. Using
      a polymerase chain reaction-based approach, we have characterized LeFPS1, a
      tomato (Lycoperscion esculentum cv Wva 106) fruit cDNA, which encodes a
      functional FPS. We demonstrate that tomato FPSs are encoded by a small multigenic
      family with genes located on chromosomes 10 and 12. Consistent with farnesyl
      pyrophosphate requirement in sterol biosynthesis, FPS genes are ubiquitously
      expressed in tomato plants. Using an LeFPS1 specific probe, we show that the
      corresponding gene can account for most of FPS mRNA in most plant organs, but not
      during young seedling development, indicating a differential regulation of FPS
      genes in tomato. FPS gene expression is also under strict developmental control:
      FPS mRNA was mainly abundant in young organs and decreased as organs matured with
      the exception of fruits that presented a biphasic accumulation pattern. In this
      latter case in situ hybridization studies have shown that FPS mRNA is similarly
      abundant in all tissues of young fruit. Taken together our results suggest that
      several FPS isoforms are involved in tomato farnesyl pyrophosphate metabolism and
      that FPS genes are mostly expressed in relation to cell division and enlargement.

PMID- 10938356
TI  - Production and characterization of diverse developmental mutants of Medicago
      truncatula.
AB  - The diploid annual legume Medicago truncatula has been developed as a tractable
      genetic system for studying biological questions that are unique to, or well
      suited for study in legume species. An efficient mutagenesis protocol using ethyl
      methyl sulfonate and a polymorphic ecotype with properties appropriate for use as
      a mapping parent are described. Isolation and characterization of three
      developmental mutants are described. The mtapetala mutation results in homeotic
      conversions of floral organ whorls 2 and 3 into sepals and carpelloid structures,
      respectively, similar to mutations in the apetala3/pistillata genes of
      Arabidopsis. The palmyra mutation primarily affects seedling shoot meristem
      initiation, and thus phenocopies meristem function mutations identified in
      Arabidopsis such as the zwille locus. The phenotype of the palmyra and mtapetala
      double mutant is additive, with seedling shoot meristems and floral organs
      indistinguishable from those of the single palmyra and mtapetala mutants,
      respectively. These results are consistent with a lack of genetic interaction
      between these loci. A third mutant, speckle, is characterized by spontaneous
      necrotic lesion formation on leaves, root, and stems, similar to necrosis mutants
      identified in other plant species. In addition to documenting the efficient
      mutagenesis of M. truncatula, the availability of developmental mutants that
      phenocopy characterized Arabidopsis mutants will provide a basis for establishing
      orthologous gene function between M. truncatula and Arabidopsis, once the genes
      responsible are cloned. Moreover, the male-sterile, female-fertile nature of the
      mtapetala mutant provides a convenient tool for genetic analyses in M.
      truncatula.

PMID- 10938355
TI  - Analysis of the N gene hypersensitive response induced by a fluorescently tagged
      tobacco mosaic virus.
AB  - The hypersensitive response (HR) triggered on Nicotiana edwardsonii by tobacco
      mosaic virus was studied using a modified viral genome that directed expression
      of the green fluorescent protein. Inoculated plants were initially incubated at
      32 degrees C to inhibit the N gene-mediated HR. Transfer to 20 degrees C
      initiated the HR, and fluorescent infection foci were monitored for early HR
      associated events. Membrane damage, which preceded visible cell collapse by more
      than 3 h, was accompanied by a transient restriction of the xylem within
      infection sites. Following cell collapse and the rapid desiccation of tissue
      undergoing the HR, isolated, infected cells were detected at the margin of
      necrotic lesions. These virus-infected cells were able to reinitiate infection on
      transfer to 32 degrees C, however, if maintained at 20 degrees C they eventually
      died. The results indicate that the tobacco mosaic virus-induced HR is a two
      phase process with an early stage culminating in rapid cell collapse and tissue
      desiccation followed by a more extended period during which the remaining
      infected cells are eliminated.

PMID- 10938357
TI  - Limited correlation between expansin gene expression and elongation growth rate.
AB  - The aim of this work was to study the role of the cell wall protein expansin in
      elongation growth. Expansins increase cell wall extensibility in vitro and are
      thought to be involved in cell elongation. Here, we studied the regulation of two
      tomato (Lycopersicon esculentum cv Moneymaker) expansin genes, LeExp2 and
      LeExp18, in rapidly expanding tissues. LeExp2 was strongly expressed in the
      elongation zone of hypocotyls and in the faster growing stem part during
      gravitropic stimulation. LeExp18 expression did not correlate with elongation
      growth. Exogenous application of hormones showed a substantial auxin-stimulation
      of LeExp2 mRNA in etiolated hypocotyls and a weaker auxin-stimulation of LeExp18
      mRNA in stem tissue. Analysis of transcript accumulation revealed higher levels
      of LeExp2 and LeExp18 in light-treated, slow-growing tissue than in dark-treated,
      rapidly elongating tissue. Expansin protein levels and cell wall extension
      activities were similar in light- and dark-grown hypocotyl extracts. The results
      show a strong correlation between expansin gene expression and growth rate, but
      this correlation is not absolute. We conclude that elongation growth is likely to
      be controlled by expansin acting in concert with other factors that may limit
      growth under some physiological conditions.

PMID- 10938358
TI  - Kinetics of photoacclimation in response to a shift to high light of the red alga
      Rhodella violacea adapted to low irradiance.
AB  - The unicellular rhodophyte Rhodella violacea can adapt to a wide range of
      irradiances. To create a light stress, cells acclimated to low light were
      transferred to higher irradiance and the kinetics of various changes produced by
      the light shift were analyzed. The proton gradient generated by excess light led
      to a non-photochemical quenching of the chlorophyll fluorescence and some
      photoinhibition of photosystem II centers was also produced by the light stress.
      After the shift to higher irradiance, the mRNA levels of three chloroplast genes
      that encode phycoerythrin and phycocyanin apoproteins and heme oxygenase (the
      first enzyme specific to the bilin synthesis) were negatively regulated. A change
      in the amount of thylakoids and in the total pigment content of the cells
      occurred during light acclimation after a light stress. The change in the size of
      the phycobilisome was limited to dissapearance of the terminal phycoerythrin
      hexamers in some of the rods. The ability of R. violacea to photoacclimate
      depends both on large changes in thylakoid number and pigment content and on
      smaller changes in the antenna size of photosystem II.

PMID- 10938359
TI  - A plastid terminal oxidase associated with carotenoid desaturation during
      chromoplast differentiation.
AB  - The Arabidopsis IMMUTANS gene encodes a plastid homolog of the mitochondrial
      alternative oxidase, which is associated with phytoene desaturation. Upon
      expression in Escherichia coli, this protein confers a detectable cyanide
      resistant electron transport to isolated membranes. In this assay this activity
      is sensitive to n-propyl-gallate, an inhibitor of the alternative oxidase. This
      protein appears to be a plastid terminal oxidase (PTOX) that is functionally
      equivalent to a quinol:oxygen oxidoreductase. This protein was immunodetected in
      achlorophyllous pepper (Capsicum annuum) chromoplast membranes, and a
      corresponding cDNA was cloned from pepper and tomato (Lycopersicum esculentum)
      fruits. Genomic analysis suggests the presence of a single gene in these
      organisms, the expression of which parallels phytoene desaturase and zeta
      carotene desaturase gene expression during fruit ripening. Furthermore, this PTOX
      gene is impaired in the tomato ghost mutant, which accumulates phytoene in leaves
      and fruits. These data show that PTOX also participates in carotenoid
      desaturation in chromoplasts in addition to its role during early chloroplast
      development.

PMID- 10938360
TI  - Transgenic tobacco and Arabidopsis plants expressing the two multifunctional
      sorghum cytochrome P450 enzymes, CYP79A1 and CYP71E1, are cyanogenic and
      accumulate metabolites derived from intermediates in Dhurrin biosynthesis.
AB  - Novel cyanogenic plants have been generated by the simultaneous expression of the
      two multifunctional sorghum (Sorghum bicolor [L.] Moench) cytochrome P450 enzymes
      CYP79A1 and CYP71E1 in tobacco (Nicotiana tabacum cv Xanthi) and Arabidopsis
      under the regulation of the constitutive 35S promoter. CYP79A1 and CYP71E1
      catalyze the conversion of the parent amino acid tyrosine to p
      hydroxymandelonitrile, the aglycone of the cyanogenic glucoside dhurrin. CYP79A1
      catalyzes the conversion of tyrosine to p-hydroxyphenylacetaldoxime and CYP71E1,
      the subsequent conversion to p-hydroxymandelonitrile. p-Hydroxymandelonitrile is
      labile and dissociates into p-hydroxybenzaldehyde and hydrogen cyanide, the same
      products released from dhurrin upon cell disruption as a result of pest or
      herbivore attack. In transgenic plants expressing CYP79A1 as well as CYP71E1, the
      activity of CYP79A1 is higher than that of CYP71E1, resulting in the accumulation
      of several p-hydroxyphenylacetaldoxime-derived products in the addition to those
      derived from p-hydroxymandelonitrile. Transgenic tobacco and Arabidopsis plants
      expressing only CYP79A1 accumulate the same p-hydroxyphenylacetaldoxime-derived
      products as transgenic plants expressing both sorghum cytochrome P450 enzymes. In
      addition, the transgenic CYP79A1 Arabidopsis plants accumulate large amounts of p
      hydroxybenzylglucosinolate. In transgenic Arabidopsis expressing CYP71E1, this
      enzyme and the enzymes of the pre-existing glucosinolate pathway compete for the
      p-hydroxyphenylacetaldoxime as substrate, resulting in the formation of small
      amounts of p-hydroxybenzylglucosinolate. Cyanogenic glucosides are
      phytoanticipins, and the present study demonstrates the feasibility of expressing
      cyanogenic compounds in new plant species by gene transfer technology to improve
      pest and disease resistance.

PMID- 10938361
TI  - Ethylene perception by the ERS1 protein in Arabidopsis.
AB  - Ethylene perception in Arabidopsis is controlled by a family of five genes,
      including ETR1, ERS1 (ethylene response sensor 1), ERS2, ETR2, and EIN4. ERS1,
      the most highly conserved gene with ETR1, encodes a protein with 67% identity to
      ETR1. To clarify the role of ERS1 in ethylene sensing, we biochemically
      characterized the ERS1 protein by heterologous expression in yeast. ERS1, like
      ETR1, forms a membrane-associated, disulfide-linked dimer. In addition, yeast
      expressing the ERS1 protein contains ethylene-binding sites, indicating ERS1 is
      also an ethylene-binding protein. This finding supports previous genetic evidence
      that isoforms of ETR1 also function in plants as ethylene receptors. Further, we
      used the ethylene antagonist 1-methylcyclopropene (1-MCP) to characterize the
      ethylene-binding sites of ERS1 and ETR1. We found 1-MCP to be both a potent
      inhibitor of the ethylene-induced seedling triple response, as well as ethylene
      binding by yeast expressing ETR1 and ERS1. Yeast expressing ETR1 and ERS1 showed
      nearly identical sensitivity to 1-MCP, suggesting that the ethylene-binding sites
      of ETR1 and ERS1 have similar affinities for ethylene.

PMID- 10938362
TI  - Changes in the xanthophyll cycle and fluorescence quenching indicate light
      dependent early events in the action of paraquat and the mechanism of resistance
      to paraquat in Erigeron canadensis (L.) cronq.
AB  - Violaxanthin de-epoxidation, chlorophyll fluorescence quenching, and
      photosynthetic O(2) evolution in the presence of paraquat (Pq) were studied in
      intact attached leaves of Pq-susceptible, and Pq-resistant (PqR) biotypes of
      Erigeron canadensis under different light conditions. Initially, similar changes
      were induced in the two biotypes, but the effects relaxed only in the PqR plants,
      indicating a Pq elimination process. The penetration of Pq into the chloroplasts
      of PqR plants proved to be somewhat restricted and highly light-dependent, as
      revealed by both the light response curves of violaxanthin de-epoxidation and
      fluorescence quenching and the short-term high-light pre-illumination
      experiments. An irregular down-regulation of the non-photochemical fluorescence
      quenching processes was observed, reflected by lower steady-state zeaxanthin and
      non-photochemical fluorescence quenching levels as compared with the
      corresponding non-treated high-light controls. It is concluded that light is
      essential not only for the initiation of the mechanism of resistance to Pq, but
      also for the penetration of Pq into the chloroplasts in the PqR E. canadensis.
      Also, the Pq elimination process may cause a modification to the regulation of
      the non-radiative energy dissipation in PqR plants in the presence of Pq.

PMID- 10938363
TI  - A minimal serine/threonine protein kinase circadianly regulates
      phosphoenolpyruvate carboxylase activity in crassulacean acid metabolism-induced
      leaves of the common ice plant.
AB  - Plant phosphoenolpyruvate carboxylase (PEPc) activity and allosteric properties
      are regulated by PEPc kinase (PPcK) through reversible phosphorylation of a
      specific serine (Ser) residue near the N terminus. We report the molecular
      cloning of PPcK from the facultative Crassulacean acid metabolism (CAM) common
      ice plant (Mesembryanthemum crystallinum), using a protein-kinase-targeted
      differential display reverse transcriptase-polymerase chain reaction approach. M.
      crystallinum PPcK encodes a minimal, Ca(2+)-independent Ser/threonine protein
      kinase that is most closely related to calcium-dependent protein kinases, yet
      lacks both the calmodulin-like and auto-inhibitory domains typical of plant
      calcium-dependent protein kinase. In the common ice plant PPcK belongs to a small
      gene family containing two members. McPPcK transcript accumulation is controlled
      by a circadian oscillator in a light-dependent manner. McPPcK encodes a 31.8-kD
      polypeptide (279 amino acids), making it among the smallest protein kinases
      characterized to date. Initial biochemical analysis of the purified, recombinant
      McPPcK gene product documented that this protein kinase specifically
      phosphorylates PEPc from CAM and C(4) species at a single, N-terminal Ser
      (threonine) residue but fails to phosphorylate mutated forms of C(4) PEPc in
      which this specific site has been changed to tyrosine or aspartate. McPPcK
      activity was specific for PEPc, Ca(2+)-insensitive, and displayed an alkaline pH
      optimum. Furthermore, recombinant McPPcK was shown to reverse the sensitivity of
      PEPc activity to L-malate inhibition in CAM-leaf extracts prepared during the
      day, but not at night, documenting that PPcK contributes to the circadian
      regulation of photosynthetic carbon flux in CAM plants.

PMID- 10938364
TI  - Assembly, secretion, and vacuolar delivery of a hybrid immunoglobulin in plants.
AB  - Secretory immunoglobulin (Ig) A is a decameric Ig composed of four alpha-heavy
      chains, four light chains, a joining (J) chain, and a secretory component (SC).
      The heavy and light chains form two tetrameric Ig molecules that are joined by
      the J chain and associate with the SC. Expression of a secretory monoclonal
      antibody in tobacco (Nicotiana tabacum) has been described: this molecule
      (secretory IgA/G [SIgA/G]) was modified by having a hybrid heavy chain sequence
      consisting of IgG gamma-chain domains linked to constant region domains of an IgA
      alpha-chain. In tobacco, about 70% of the protein assembles to its final,
      decameric structure. We show here that SIgA/G assembly and secretion are slow,
      with only approximately 10% of the newly synthesized molecules being secreted
      after 24 h and the bulk probably remaining in the endoplasmic reticulum. In
      addition, a proportion of SIgA/G is delivered to the vacuole as at least
      partially assembled molecules by a process that is blocked by the membrane
      traffic inhibitor brefeldin A. Neither the SC nor the J chain are responsible for
      vacuolar delivery, because IgA/G tetramers have the same fate. The parent IgG
      tetrameric molecule, containing wild-type gamma-heavy chains, is instead secreted
      rapidly and efficiently. This strongly suggests that intracellular retention and
      vacuolar delivery of IgA/G is due to the alpha-domains present in the hybrid
      alpha/gamma-heavy chains and indicates that the plant secretory system may
      partially deliver to the vacuole recombinant proteins expected to be secreted.

PMID- 10938365
TI  - At-ACA8 encodes a plasma membrane-localized calcium-ATPase of Arabidopsis with a
      calmodulin-binding domain at the N terminus.
AB  - A Ca(2+)-ATPase was purified from plasma membranes (PM) isolated from Arabidopsis
      cultured cells by calmodulin (CaM)-affinity chromatography. Three tryptic
      fragments from the protein were microsequenced and the corresponding cDNA was
      amplified by polymerase chain reaction using primers designed from the
      microsequences of the tryptic fragments. At-ACA8 (Arabidopsis-autoinhibited
      Ca(2+)-ATPase, isoform 8, accession no. AJ249352) encodes a 1,074 amino acid
      protein with 10 putative transmembrane domains, which contains all of the
      characteristic motifs of Ca(2+)-transporting P-type Ca(2+)-ATPases. The identity
      of At-ACA8p as the PM Ca(2+)-ATPase was confirmed by immunodetection with an
      antiserum raised against a sequence (valine-17 through threonine-31) that is not
      found in other plant CaM-stimulated Ca(2+)-ATPases. Confocal fluorescence
      microscopy of protoplasts immunodecorated with the same antiserum confirmed the
      PM localization of At-ACA8. At-ACA8 is the first plant PM localized Ca(2+)-ATPase
      to be cloned and is clearly distinct from animal PM Ca(2+)-ATPases due to the
      localization of its CaM-binding domain. CaM overlay assays localized the CaM
      binding domain of At-ACA8p to a region of the N terminus of the enzyme around
      tryptophan-47, in contrast to a C-terminal localization for its animal
      counterparts. Comparison between the sequence of At-ACA8p and those of
      endomembrane-localized type IIB Ca(2+)-ATPases of plants suggests that At-ACA8 is
      a representative of a new subfamily of plant type IIB Ca(2+)-ATPases.

PMID- 10938366
TI  - Elicitation of suspension-cultured tomato cells triggers the formation of
      phosphatidic acid and diacylglycerol pyrophosphate.
AB  - Phosphatidic acid (PA) and its phosphorylated derivative diacylglycerol
      pyrophosphate (DGPP) are lipid molecules that have been implicated in plant cell
      signaling. In this study we report the rapid but transient accumulation of PA and
      DGPP in suspension-cultured tomato (Lycopersicon esculentum) cells treated with
      the general elicitors, N,N',N",N"'-tetraacetylchitotetraose, xylanase, and the
      flagellin-derived peptide flg22. To determine whether PA originated from the
      activation of phospholipase D or from the phosphorylation of diacylglycerol (DAG)
      by DAG kinase, a strategy involving differential radiolabeling with
      [(32)P]orthophosphate was used. DAG kinase was found to be the dominant producer
      of PA that was subsequently metabolized to DGPP. A minor but significant role for
      phospholipase D could only be detected when xylanase was used as elicitor. Since
      PA formation was correlated with the high turnover of polyphosphoinositides, we
      hypothesize that elicitor treatment activates phospholipase C to produce DAG,
      which in turn acts as substrate for DAG kinase. The potential roles of PA and
      DGPP in plant defense signaling are discussed.

PMID- 10938367
TI  - Fluoroorotic acid-selected Nicotiana plumbaginifolia cell lines with a stable
      thymine starvation phenotype have lost the thymine-regulated transcriptional
      program.
AB  - We have selected 143 independent Nicotiana plumbaginifolia cell lines that
      survive in the presence of 5-fluoroorotic acid. These lines show several diverse
      phenotypes. The majority of these cell lines showed reduced levels of UMP
      synthase. However, one particular phenotype, which represents 14% of the total
      independent lines (20 cell lines), showed an unexpected, high level of UMP
      synthase and was therefore analyzed in detail. The selected cell lines showed no
      differences with wild-type cells with respect to uptake of orotic acid, affinity
      of UMP synthase for its substrates, or UMP synthase gene-copy number. Alternative
      detoxification mechanisms were also excluded. The elevated enzyme activity was
      correlated with elevated UMP synthase protein levels as well as elevated UMP
      synthase mRNA levels. In contrast to wild-type cell lines, the fluoroorotic acid
      selected cell lines did not respond to thymine or to other biochemicals that
      affect thymine levels. In addition, there was also a concomitant up-regulation of
      aspartate transcarbamoylase, however, dihydroorotase and dihydroorotate
      dehydrogenase are not up-regulated in these cell lines.

PMID- 10938368
TI  - Dephosphorylation of photosystem II reaction center proteins in plant
      photosynthetic membranes as an immediate response to abrupt elevation of
      temperature.
AB  - Kinetic studies of protein dephosphorylation in photosynthetic thylakoid
      membranes revealed specifically accelerated dephosphorylation of photosystem II
      (PSII) core proteins at elevated temperatures. Raising the temperature from 22
      degrees C to 42 degrees C resulted in a more than 10-fold increase in the
      dephosphorylation rates of the PSII reaction center proteins D1 and D2 and of the
      chlorophyll a binding protein CP43 in isolated spinach (Spinacia oleracea)
      thylakoids. In contrast the dephosphorylation rates of the light harvesting
      protein complex and the 9-kD protein of the PSII (PsbH) were accelerated only 2-
      to 3-fold. The use of a phospho-threonine antibody to measure in vivo
      phosphorylation levels in spinach leaves revealed a more than 20-fold
      acceleration in D1, D2, and CP43 dephosphorylation induced by abrupt elevation of
      temperature, but no increase in light harvesting protein complex
      dephosphorylation. This rapid dephosphorylation is catalyzed by a PSII-specific,
      intrinsic membrane protein phosphatase. Phosphatase assays, using intact
      thylakoids, solubilized membranes, and the isolated enzyme, revealed that the
      temperature-induced lateral migration of PSII to the stroma-exposed thylakoids
      only partially contributed to the rapid increase in the dephosphorylation rate.
      Significant activation of the phosphatase coincided with the temperature-induced
      release of TLP40 from the membrane into thylakoid lumen. TLP40 is a peptidyl
      prolyl cis-trans isomerase, which acts as a regulatory subunit of the membrane
      phosphatase. Thus dissociation of TLP40 caused by an abrupt elevation in
      temperature and activation of the membrane protein phosphatase are suggested to
      trigger accelerated repair of photodamaged PSII and to operate as possible early
      signals initiating other heat shock responses in chloroplasts.

PMID- 10938369
TI  - Pattern of aluminum-induced secretion of organic acids differs between rye and
      wheat.
AB  - Al-Induced secretion of organic acids from the roots has been considered as a
      mechanism of Al tolerance, but the processes leading to the secretion of organic
      acids are still unknown. In this study, the secretion pattern and alteration in
      the metabolism of organic acids under Al stress were examined in rye (Secale
      cereale L. cv King) and wheat (Triticum aestivum L. cv Atlas 66). Al induced
      rapid secretion of malate in the wheat, but a lag (6 and 10 h for malic and
      citric acids, respectively) between the exposure to Al and the secretion of
      organic acids was observed in the rye. The activities of isocitrate
      dehydrogenase, phosphoenolpyruvate carboxylase, and malate dehydrogenase were not
      affected by Al in either plant. The activity of citrate synthase was increased by
      the exposure to Al in the rye, but not in the wheat. The secretion of malate was
      not suppressed at low temperature in the wheat, but that of citrate was stopped
      in the rye. The Al-induced secretion of citrate from roots of the rye was
      inhibited by the inhibitors of a citrate carrier, which transports citrate from
      the mitochondria to the cytoplasm. All of these results suggest that alteration
      in the metabolism of organic acids is involved in the Al-induced secretion of
      organic acids in rye, but only activation of an anion channel seems to be
      responsible for the rapid secretion of malate in the wheat.

PMID- 10938370
TI  - A dual function alpha-dioxygenase-peroxidase and NAD(+) oxidoreductase active
      enzyme from germinating pea rationalizing alpha-oxidation of fatty acids in
      plants.
AB  - An enzyme with fatty acid alpha-oxidation activity (49 nkat mg(-1); substrate:
      lauric acid) was purified from germinating pea (Pisum sativum) by a five-step
      procedure to apparent homogeneity. The purified protein was found to be a 230-kD
      oligomer with two dominant subunits, i.e. a 50-kD subunit with NAD(+)
      oxidoreductase activity and a 70-kD subunit, homolog to a pathogen-induced
      oxygenase, which in turn shows significant homology to animal cyclooxygenase. On
      line liquid chromatography-electrospray ionization-tandem mass spectrometry
      revealed rapid alpha-oxidation of palmitic acid incubated at 0 degrees C with the
      purified alpha-oxidation enzyme, leading to (R)-2-hydroperoxypalmitic acid as the
      major product together with (R)-2-hydroxypalmitic acid, 1-pentadecanal, and
      pentadecanoic acid. Inherent peroxidase activity of the 70-kD fraction decreased
      the amount of the (R)-2-hydroperoxy product rapidly and increased the level of
      (R)-2-hydroxypalmitic acid. Incubations at room temperature accelerated the
      decline toward the chain-shortened aldehyde. With the identification of the dual
      function alpha-dioxygenase-peroxidase (70-kD unit) and the related NAD(+)
      oxidoreductase (50-kD unit) we provided novel data to rationalize all steps of
      the classical scheme of alpha-oxidation in plants.

PMID- 10938371
TI  - Trivalent ions activate abscisic acid-inducible promoters through an ABI1
      dependent pathway in rice protoplasts.
AB  - The plant hormone abscisic acid (ABA) mediates many vital processes in plant
      growth and development, including seed dormancy, cell division, water use
      efficiency, and adaptation to drought, salinity, chilling, pathogen attack, and
      UV light. Our understanding of ABA signal transduction is fragmentary and would
      benefit from specific and facile probes of the process. Protoplasts from rice
      (Oryza sativa L. cv IR54) embryonic suspension cultures cotransformed with
      effector plasmids encoding the maize (Zea mays) VIVIPAROUS1 cDNA and/or the
      Arabidopsis dominant negative mutant (abi1-1) ABA-insensitive cDNA demonstrated
      genetic interactions of VIVIPAROUS1 and abi1-1 in transactivation of the ABA
      inducible HVA1 promoter from barley (Hordeum vulgare), suggesting the mechanisms
      of these effectors are conserved among monocots and dicots. Trivalent ions have
      been shown to act as an effector of gene expression in plants and animals,
      although the mechanism of action is unknown. We show in two complementary
      transient ABA-inducible gene expression assays (beta-glucuronidase and luciferase
      enzymatic activities and quantitative flow cytometry of green fluorescent
      protein) that trivalent ions specifically interact with an ABI1-dependent ABA
      signaling pathway leading to gene expression. Trivalent ions mimic ABA effects on
      gene expression and may be a useful tool to study ABA signaling.

PMID- 10938372
TI  - AN9, a petunia glutathione S-transferase required for anthocyanin sequestration,
      is a flavonoid-binding protein.
AB  - AN9 is a glutathione S-transferase from petunia (Petunia hybrida) required for
      efficient anthocyanin export from the site of synthesis in the cytoplasm into
      permanent storage in the vacuole. For many xenobiotics it is well established
      that a covalent glutathione (GSH) tag mediates recognition of molecules destined
      for vacuolar sequestration by a tonoplast-localized ATP-binding cassette pump.
      Here we inquired whether AN9 catalyzes the formation of GSH conjugates with
      flavonoid substrates. Using high-performance liquid chromatography analysis of
      reaction mixtures containing enzyme, GSH, and flavonoids, including anthocyanins,
      we could detect neither conjugates nor a decrease in the free thiol
      concentration. These results suggest that no conjugate is formed in vitro.
      However, AN9 was shown to bind flavonoids using three assays: inhibition of the
      glutathione S-transferase activity of AN9 toward the common substrate 1-chloro
      2,4-dinitrobenzene, equilibrium dialysis, and tryptophan quenching. We conclude
      that AN9 is a flavonoid-binding protein, and propose that in vivo it serves as a
      cytoplasmic flavonoid carrier protein.

PMID- 10938373
TI  - Characterization and expression of DNA sequences encoding putative type-II
      metallothioneins in the seagrass Posidonia oceanica.
AB  - Posidonia oceanica is a marine phanerogam, largely widespread in the
      Mediterranean sea, representing an important food substrate for many marine
      organisms. A progressive reduction of P. oceanica meadows has been reported, due
      to anthropogenic coastal activity. Studying mechanisms by which this species
      responds to environmental stresses, three DNA sequences putatively encoding
      metallothioneins (MTs) have been isolated, by PCR. Two sequences, Pomt2a
      (accession no. AJ249603) and Pomt2b (accession no. AJ249602), show high
      similarities with genes encoding type-II MTs and are interrupted by two and one
      intron, respectively. The third sequence, Pomt2c (accession no. AJ249604), is
      supposed to be a pseudogene, originated by retrotranscription of the Pomt2b mRNA.
      These sequences belong to a multigene family with at least five members. Northern
      hybridizations indicated that MT transcripts accumulation is constitutive and
      seasonally regulated. MT encoding RNAs increase after rhyzome harvesting and (at
      a lesser extent) after 15 d of cultivation in an aquarium. As for animal MTs,
      transcripts accumulation is observed also after exposure to trace metals such as
      copper and cadmium. In the case of copper, the effect depends on concentration.
      Finally, taking into consideration the great interest in studying the
      biogeochemical cycle of mercury in the Mediterranean basin and since P. oceanica
      is commonly considered a bioindicator of this metal, the effect of mercury
      treatments on the accumulation of MT transcripts has been analyzed: in only a few
      experiments a small increase in the level of transcripts was recorded, suggesting
      that MTs are not key elements in the mercury accumulation by this species.

PMID- 10938374
TI  - Detection of expansin proteins and activity during tomato fruit ontogeny.
AB  - Expansins are plant proteins that have the capacity to induce extension in
      isolated cell walls and are thought to mediate pH-dependent cell expansion.
      J.K.C. Rose, H.H. Lee, and A.B. Bennett ([1997] Proc Natl Acad Sci USA 94: 5955
      5960) reported the identification of an expansin gene (LeExp1) that is
      specifically expressed in ripening tomato (Lycopersicon esculentum) fruit where
      cell wall disassembly, but not cell expansion, is prominent. Expansin expression
      during fruit ontogeny was examined using antibodies raised to recombinant LeExp1
      or a cell elongation-related expansin from cucumber (CsExp1). The LeExp1
      antiserum detected expansins in extracts from ripe, but not preripe tomato fruit,
      in agreement with the pattern of LeExp1 mRNA accumulation. In contrast,
      antibodies to CsExp1 cross-reacted with expansins in early fruit development and
      the onset of ripening, but not at a later ripening stage. These data suggest that
      ripening-related and expansion-related expansin proteins have distinct antigenic
      epitopes despite overall high sequence identity. Expansin proteins were detected
      in a range of fruit species and showed considerable variation in abundance;
      however, appreciable levels of expansin were not present in fruit of the rin or
      Nr tomato mutants that exhibit delayed and reduced softening. LeExp1 protein
      accumulation was ethylene-regulated and matched the previously described
      expression of mRNA, suggesting that expression is not regulated at the level of
      translation. We report the first detection of expansin activity in several stages
      of fruit development and while characteristic creep activity was detected in
      young and developing tomato fruit and in ripe pear, avocado, and pepper, creep
      activity in ripe tomato showed qualitative differences, suggesting both
      hydrolytic and expansin activities.

PMID- 10938375
TI  - The forms and sources of cytokinins in developing white lupine seeds and fruits.
AB  - A comprehensive range of cytokinins (CK) was identified and quantified by gas
      chromatography-mass spectrometry in tissues of and in xylem and phloem serving
      developing white lupine (Lupinus albus) fruits. Analyses were initiated at
      anthesis and included stages of podset, embryogenesis, and seed filling up to
      physiological maturation 77 d post anthesis (DPA). In the first 10 DPA,
      fertilized ovaries destined to set pods accumulated CK. The proportion of cis
      CK:trans-CK isomers was initially 10:1 but declined to less than 1:1. In ovaries
      destined to abort, the ratio of cis-isomers to trans-isomers remained high.
      During early podset, accumulation of CK (30-40 pmol ovary(-1)) was accounted for
      by xylem and phloem translocation, both containing more than 90% cis-isomers.
      During embryogenesis and early seed filling (40-46 DPA), translocation accounted
      for 1% to 14% of the increases of CK in endosperm (20 nmol fruit(-1)) and seed
      coat (15 nmol fruit(-1)), indicating synthesis in situ. High CK concentrations in
      seeds (0.6 micromol g(-1) fresh weight) were transient, declining rapidly to less
      than 1% of maximum levels by physiological maturity. These data pose new
      questions about the localization and timing of CK synthesis, the significance of
      translocation, and the role(s) of CK forms in reproductive development.

PMID- 10938376
TI  - Emission of isoprene from salt-stressed Eucalyptus globulus leaves.
AB  - Eucalyptus spp. are among the highest isoprene emitting plants. In the
      Mediterranean area these plants are often cultivated along the seashore and cope
      with recurrent salt stress. Transient salinity may severely but reversibly reduce
      photosynthesis and stomatal conductance of Eucalyptus globulus leaves but the
      effect on isoprene emission is not significant. When the stress is relieved, a
      burst of isoprene emission occurs, simultaneously with the recovery of
      photosynthetic performance. Later on, photosynthesis, stomatal conductance, and
      isoprene emission decay, probably because of the onset of leaf senescence.
      Isoprene emission is not remarkably affected by the stress at different light
      intensities, CO(2) concentrations, and leaf temperatures. When CO(2) was removed
      and O(2) was lowered to inhibit both photosynthesis and photorespiration, we
      found that the residual emission is actually higher in salt-stressed leaves than
      in controls. This stimulation is particularly evident at high-light intensities
      and high temperatures. The maximum emission occurs at 40 degrees C in both salt
      stressed and control leaves sampled in ambient air and in control leaves sampled
      in CO(2)-free and low-O(2) air. However, the maximum emission occurs at 45
      degrees C in salt-stressed leaves sampled in CO(2)-free and low-O(2) air. Our
      results suggest the activation of alternative non-photosynthetic pathways of
      isoprene synthesis in salt-stressed leaves and perhaps in general in leaves
      exposed to stress conditions. The temperature dependence indicates that this
      alternative synthesis is also under enzymatic control. If this alternative
      synthesis still occurs in the chloroplasts, it may involve a thylakoid-bound
      isoprene synthase.

PMID- 10938377
TI  - Induction of a C(4)-like mechanism of CO(2) fixation in Egeria densa, a submersed
      aquatic species.
AB  - The expression of phosphoenolpyruvate carboxylase (PEPC) and NADP-malic enzyme
      (NADP-ME) in Egeria densa leaves was studied under low temperature and light
      (LTL) following incubation under high temperature and light (HTL), conditions
      previously shown to induce high and low CO(2) compensation points, respectively.
      Transfer from LTL to HTL conditions induced increases in the activities and
      amounts of both enzymes. One NADP-ME isoform was observed in induced and
      uninduced samples. Two isoforms of PEPC were expressed, with the lower M(r)
      isoform being induced by HTL. NADP-ME showed properties similar to those of the
      isoform in C(3) species. The inducible PEPC isoform has a low K(m) for both
      substrates. PEPC kinetic and regulatory properties (V(max) and K(m) for
      phosphoenolpyruvate, and I(50) for L-malate) are different in samples taken in
      the dark from those in the light, indicating that some modification of PEPC may
      be occurring during the day. Finally, abscisic acid induced the expression of
      PEPC and NADP-ME in a manner similar to temperature induction, except that the
      activities of both PEPC isoforms were increased. A different signaling system may
      exist in this species in response to high temperature or abscisic acid, both of
      which induce changes in photosynthetic metabolism.

PMID- 10938379
TI  - A G2/M growth arrest response to low-dose intermittent H2O2 in normal
      uroepithelial cells.
AB  - Studies in fibroblasts have shown that H2O2, as a model for oxidative damage,
      leads to a G1 growth arrest phenotypically similar to senescence. These
      observations as well as the observation that bladder cancer is associated with
      deletions of CDKN2, a gene important in normal senescence, led us to examine
      normal urothelial cell response to H2O2. We hypothesized that low dose H2O2
      exposure would lead to p16 and/or p14arf mediated senescence. We show that H2O2
      leads to endogenous beta-galactosidase expression similar to senescence, but
      instead of G1 arrest, it leads to G2/M growth arrest without induction of either
      p16 or p14arf. Lack of p21 induction and a similar G2/M growth arrest in E6
      immortalized uroepithelial cells suggests that this response is independent of
      p53 as well. An increased level of cdc2 tyrosine-15 phosphorylation following
      H2O2 treatment suggests that the observed growth arrest is mediated by a G2
      checkpoint mechanism.

PMID- 10938380
TI  - Fibrous tumors in children - a morphologic and interphase cytogenetic analysis of
      problematic cases.
AB  - We describe and discuss the findings by fluorescent in situ hybridization (FISH)
      for detection of non-random chromosomal gains, in a group of unusual fibrous
      lesions in children. Nuclear disaggregation was used to prepare slides from eight
      cases which were hybridized using alpha-satellite enumeration probes for
      chromosomes 8, 11 and 17. Trisomy 8 and 11 were detected in a high percentage of
      nuclei in cases of congenital/infantile fibrosarcomas (ranging from 45 to 80%),
      and in a low grade fibrosarcoma in an older child (23%). Only gains of chromosome
      17 were detected in a case of infantile fibromatosis (22%). In this study we have
      found that given the unconventional histopathologic features, the detection of
      more than one non-random chromosomal gains by FISH, may aid in further defining
      fibrous tumors in children, and may be useful as an ancillary diagnostic test in
      the future.

PMID- 10938378
TI  - Identification of a CYP84 family of cytochrome P450-dependent mono-oxygenase
      genes in Brassica napus and perturbation of their expression for engineering
      sinapine reduction in the seeds.
AB  - CYP84 is a recently identified family of cytochrome P450-dependent mono
      oxygenases defined by a putative ferulate-5-hydroxylase (F5H) from Arabidopsis.
      Until recently F5H has been thought to catalyze the hydroxylation of ferulate to
      5-OH ferulate en route to sinapic acid. Sinapine, a sinapate-derived ester in the
      seeds, is antinutritional and a target for elimination in canola meal. We have
      isolated three F5H-like genes (BNF5H1-3) from a cultivated Brassica napus, whose
      amphidiploid progenitor is considered to have arisen from a fusion of the
      diploids Brassica rapa and Brassica oleracea. Two cultivated varieties of the
      diploids were also found to contain BNF5H3 and additionally either BNF5H1 or
      BNF5H2, respectively. Whereas all three are >90% identical in their coding
      sequence, BNF5H1 and BNF5H2 are closer to each other than to BNF5H3. This and
      additional data suggest that the two groups of genes have diverged in an ancestor
      of the diploids. B. napus showed maximal F5H expression in the stems, least in
      the seeds, and subtle differences among the expression profiles of the three
      genes elsewhere. Transgenic B. napus with cauliflower mosaic virus 35S-antisense
      BNF5H contained up to 40% less sinapine, from 9.0 +/- 0.3 mg in the controls to
      5.3 +/- 0.3 mg g(-1) seed. F5H from Arabidopsis and a similar enzyme from
      sweetgum (Liquidamber styraciflua) has recently been shown to have
      coniferaldehyde hydroxylase activity instead of F5H activity. Thus the supply of
      5-OH coniferaldehyde or 5-OH ferulate has a bearing on sinapine accumulation in
      canola seeds.

PMID- 10938381
TI  - Ancestrally-duplicated paraHOX gene clusters in humans.
AB  - A paraHox gene cluster has been described recently in Amphioxus. We show here
      using bioinformatics and cytogenetics that, as the probable result of the
      duplication of an ancestral paraHox gene cluster, human paraHOX genes are located
      in four paralogous regions of the genome, on chromosomes 4, 5, 13 and X. By
      analogy with the four HOX gene clusters, we propose to designate the four paraHOX
      gene clusters as paraHOX-A to D clusters. We also propose a scenario for the
      evolution of HOX and paraHOX genes. Several chromosomal translocation breakpoints
      of hemopathies are located in the paralogous regions that contain the paraHOX
      genes. Two of the paraHOX genes are involved in these rearrangements.

PMID- 10938382
TI  - Tumor associated macrophages in human prostate cancer: relation to
      clinicopathological variables and survival.
AB  - Tumor associated macrophages (TAM) influence diverse processes such as
      angiogenesis, tumor cell proliferation, and metastasis during tumor progression.
      In a variety of tumor types, the amount of TAM has been associated with
      prognosis, but their role in prostate cancer has not been elucidated. The purpose
      of this study was to investigate the role of TAM in a series of 85 cases of
      prostatic carcinoma, diagnosed at transurethral resection of the prostate between
      1975-1983, using immunohistochemistry and morphometrical techniques. Macrophage
      density was assessed as the maximum number of TAM per field in the three most
      macrophage dense areas (TAMmax) and as the average volume density of TAM in an
      estimate of the whole resected tumor. Furthermore, the individual cell profile
      area of TAM was assessed with an image analyzer. Macrophage variables were
      thereafter related to histological grade, tumor stage, metastasis as well as to
      vascular density, tumor cell proliferation and survival. Patients with a volume
      density of TAM in the fourth quartile had a shorter median cancer specific
      survival time than patients in the first to third quartile (3.3 vs. 5.9 years,
      p=0.005). Furthermore, an increased macrophage cell profile area was related to
      poor clinical outcome (4.6 vs. 5.9 years, p=0.039) whereas TAMmax gave no
      prognostic information. In a multivariate analysis, metastasis and the volume
      density of macrophages gave independent prognostic information (p=0.0008,
      p=0.010). However, when excluding metastasis from the analysis, only Gleason
      score was an independent predictor of cancer specific survival (p= 0.005). The
      volume density of TAM, the macrophage cell profile area and TAMmax increased with
      increasing Gleason score (p=0.001, p=0.0001, p=0.0001 respectively). A
      correlation was found between the volume density of TAM and tumor cell
      proliferation (rs=0.44, p=0.001) and an increased macrophage cell profile area
      was associated to microvessel density (rs=0.42, p=0.0001). Together these results
      suggest that both the functional state (as reflected by cell size), number and
      location of the macrophages are of importance for their influence on prostate
      tumors, but macrophage quantification is not a strong independent prognostic
      factor.

PMID- 10938384
TI  - Immunolocalization of transforming growth factor-betas and their receptors in the
      intervertebral disk of senescence-accelerated mouse.
AB  - The temporal and spatial immunolocalization of TGF-betas and their receptors in
      the intervertebral disk of senescence-accelerated mouse (SAM) was examined to
      determine the biological roles played by TGF-betas and their receptors in the
      process of intervertebral disk degeneration. Ten male SAM and ICR mice aged 8, 24
      or 50 weeks after birth were used for this experiment. Histological and
      immunohistochemical studies using specific antibodies for TGF-beta1, -beta2, 
      beta3, TbetaR-I, and TbetaR-II were performed. Intervertebral disks of SAM
      exhibited more degenerative changes than those of ICR mice. Expression of TGF
      betas and TbetaRs in disk of SAM and ICR mice was observed at 8 weeks of age, and
      became weaker with aging. Our results suggest TGF-betas may play a role in the
      growth and maintenance of intervertebal disks.

PMID- 10938383
TI  - TGF-alpha as well as VEGF, PD-ECGF and bFGF contribute to angiogenesis of
      esophageal squamous cell carcinoma.
AB  - It has been demonstrated that vascular endothelial growth factor (VEGF) is
      associated with tumor progression as an angiogenic factor in esophageal squamous
      cell carcinoma (SCC)s. However, the role of other angiogenic factors such as
      transforming growth factor-alpha (TGF-alpha), platelet-derived endothelial cell
      growth factor (PD-ECGF), and basic fibroblast growth factor (bFGF) are still
      unknown in esophageal SCCs. In this study, we detected the expression of VEGF,
      TGF-alpha, PD-ECGF and bFGF in tissue specimens from 96 patients with SCC of the
      esophagus by immunohistochemical staining. To evaluate angiogenesis, endothelial
      cells were stained immunohistochemically and microvessel density (MVD) was
      counted in 24 cases. The positive rates for VEGF, TGF-alpha, PD-ECGF and bFGF
      were 65% (62/96), 67% (64/96), 66% (63/96), and 49% (47/96), respectively. Only
      TGF-alpha expression had a strong correlation with the average MVD (p=0.0059).
      However, the MVD increased as the number of positive factors for these 4 factors
      increased (p=0.0023). The expression of all of these factors significantly
      correlated to the depth of tumor invasion, and lymph node metastasis. Finally,
      survival analysis of the patients revealed that VEGF, TGF-alpha, and PD-ECGF were
      significant prognostic factors. However, multivariate analysis revealed that
      these factors were not prognostic. Thus, we suggest that TGF-alpha as well as
      VEGF, PD-ECGF and bFGF may be associated with angiogenesis, and the progression
      and metastasis of esophageal squamous cell carcinoma.

PMID- 10938385
TI  - Mutation analysis of the hMTH1 gene in sporadic human ovarian cancer.
AB  - 8-oxo-deoxyguanosine triphosphate (8-oxo-dGTP) is a major oxidation product in
      the nucleotide pool of the cell and is a potent mutagen, because it can be
      incorporated into DNA with equal frequency opposite either template C or A. The
      human MTH1 gene (hMTH1) is a homologue of the E. coli mutator gene mutT, which
      encodes 8-oxo-dGTPase. hMTH1 protein reduces spontaneous mutations by removing 8
      oxo-dGTP from the triphosphate pool. To determine whether this gene is associated
      with carcinogenesis of human ovarian cancer, the present study examined, for the
      first time, the hMTH1 sequence in 49 ovarian cancers and 9 ovarian cancer cell
      lines by means of polymerase chain reaction-single strand conformation
      polymorphism (PCR-SSCP) and sequencing analyses. A Gright curved arrow A
      transition at codon 83 was detected in one patient and one cell line (3.4%),
      followed by an amino acid change (valineright curved arrow methionine) which was
      known to cause the protein to be less active in vitro. This one base substitution
      was found in normal and corresponding tumor DNA, and its allele type was
      heterozygous. The same change has been detected in HNPCC (hereditary non
      polyposis colorectal cancer) and gastric cancer patients, and thus it may not
      represent a mutation specific for ovarian cancer. A silent Tright curved arrow C
      transition at codon 119 was detected in 12 patients and 2 cell lines (24.1%). No
      specific mutations in hMTH1 were found in either ovarian cancer patients or cell
      lines. Thus, it appears that hMTH1 is not directly associated with ovarian
      cancer.

PMID- 10938386
TI  - Deletion of one adenine base within the polyadenine tract of transforming growth
      factor-beta receptor type II in human MDA-MB-231 breast cancer cell line.
AB  - Microsatellite mutation of the polyadenine tract (10 adenine repeat) within the
      TbetaR-II [transforming growth factor-beta (TGF-beta) receptor type II] coding
      region have been found in a variety of human cancers, particularly in association
      with microsatellite instability (MSI). Since breast cancers have been reported to
      carry MSI, although its frequencies were quite variable, we examined whether
      microsatellite mutation of the polyadenine tract occurs in the human breast
      cancer MDA-MB-231 cell line. TbetaR-II expression in MDA-MB-231 was found to be
      low on our Northern and Western analyses. Sequencing analysis for the polyadenine
      tract of TbetaR-II cDNA obtained from MDA-MB-231 cells indicated heterozygous
      deletion of one adenine base. Subsequently, sensitivity to TGF-beta induced
      growth-inhibitory effects of control and TbetaR-II transfected MDA-MB-231 cells
      was compared. The sensitivity of TbetaR-II transfectants to exogenous as well as
      endogenous TGF-beta1 was increased distinctly compared with control transfectant.
      These results suggest that heterozygous deletion of one adenine base within the
      polyadenine tract in MDA-MB-231 cells might lead to reduced TbetaR-II expression
      and sensitivity to TGF-beta.

PMID- 10938387
TI  - Increased ICAM-1 expression in transformed human oral epithelial cells: molecular
      mechanism and functional role in peripheral blood mononuclear cell adhesion and
      lymphokine-activated-killer cell cytotoxicity.
AB  - The intercellular adhesion molecule-1 (ICAM-1, CD54) serves as a counter-receptor
      for the beta2-integrins, LFA-1 and Mac-1, which are expressed on leukocytes.
      Although expression of ICAM-1 on tumor cells has a role in tumor progression and
      development, information on ICAM-1 expression and its role in oral cancer has not
      been established. Normal human oral keratinocytes (NHOK), human papilloma virus
      (HPV)-immortalized human oral keratinocyte lines (HOK-16B, HOK-18A, and HOK-18C),
      and six human oral neoplastic cell lines (HOK-16B-BaP-T1, SCC-4, SCC-9, HEp-2, Tu
      177 and 1483) were used to study ICAM-1 expression and its functional role in
      vitro. Our results demonstrated that NHOK express negligible levels of ICAM-1,
      whereas immortalized human oral keratinocytes and cancer cells express
      significantly higher levels of ICAM-1, except for HOK-16B-BaP-T1 and HEp-2.
      Altered mRNA half-lives did not fully account for the increased accumulation of
      ICAM-1 mRNA. Adhesion of peripheral blood mononuclear cells (PBMC) to epithelial
      cells correlated with cell surface ICAM-1 expression levels. This adhesion was
      inhibited by antibodies specific for either ICAM-1 or LFA-1/Mac-1, suggesting a
      role for these molecules in adhesion. In contrast, lymphokine-activated-killer
      (LAK) cell cytotoxic killing of epithelial cells did not correlate with ICAM-1
      levels or with adhesion. Nonetheless, within each cell line, blocking of ICAM-1
      or LFA-1/Mac-1 reduced LAK cell killing, suggesting that ICAM-1 is involved in
      mediating this killing.

PMID- 10938389
TI  - Hammerhead ribozyme specifically inhibits vascular endothelial growth factor gene
      expression in a human hepatocellular carcinoma cell line.
AB  - Hammerhead-type ribozymes are often utilized to suppress the expression of target
      genes. We evaluated the efficacy of an anti-vascular endothelial growth factor
      (VEGF) hammerhead-type ribozyme against GUC at exon 1 of the VEGF gene in a cell
      free system (in vitro) as well as in the hepatocellular carcinoma cell line HLF
      (in vivo). The anti-VEGF ribozyme (alphaVRz) specifically cleaved synthetic VEGF
      RNA substrate, but not other triplet sequences of VEGF RNA substrate in vitro.
      When the alphaVRz was introduced into HLF cells, the ribozyme suppressed not only
      VEGF mRNA level but also that of VEGF protein. These results suggest that this
      ribozyme selectively inhibits VEGF gene expression in human hepatocellular
      carcinoma cells.

PMID- 10938388
TI  - Phorbol 12-myristate 13-acetate induces alteration in mucin gene expression and
      biological properties of colon cancer cells.
AB  - Phorbol esters such as phorbol 12-myristate 13-acetate (PMA) have been reported
      to modulate diverse cellular responses through signal transduction pathways
      including the protein kinase C (PKC) pathway. In the present study, we sought to
      determine the effect of PMA on mucin gene expression and on the biological
      properties of a human colon cancer cell line, HM3. The cells were treated for 8
      and 24 h with various concentrations of PMA and total RNA was extracted and
      Northern and slot blot analyses were carried out using MUC2, MUC3 and MUC5AC
      mucin cDNA probes to assess the steady state levels of mRNA. Spent media were
      collected and the level of cancer associated carbohydrate antigens (T, Tn, sialyl
      Tn, sialyl Lex, and sialyl Lea) and matrix-degrading metalloproteinase (MMPs)
      activity were examined. Trypsinized cells were used for assessing in vitro
      invasion, motility and adhesion to matrigel. Our results showed that PMA caused
      upregulation of steady state mRNA levels of MUC2, MUC3 and MUC5AC which was
      inhibited after treatment with protein synthesis inhibitors. Calphostin C, a
      highly specific inhibitor of protein kinase C significantly inhibited the PMA
      induced induction of mRNA levels of MUC2, MUC3, and MUC5AC. The levels of all
      cancer-associated mucin carbohydrate antigens examined in the media were
      increased by PMA treatment. PMA also caused an increase in MMPs activity and in
      in vitro invasion and motility properties, but did not affect adhesion of HM3
      cells to matrigel. Thus, PMA caused a significant increase in the expression of
      all three mucin genes through signaling pathways involving protein kinase C and
      increased secretion of mucin associated carbohydrate antigens. These changes were
      associated with increases in MMP activity as well as by increases in the invasive
      and motility properties of HM3 colon cancer cells. These data suggest that
      protein kinase C signaling pathways may be involved in mucin gene regulation and
      in modulating the invasive and metastatic properties of colon cancer cells.

PMID- 10938390
TI  - Alteration of CDKN2/p16 in human astrocytic tumors is related with increased
      susceptibility to antimetabolite anticancer agents.
AB  - A slowly proliferating cell fraction in tumors shows reduced sensitivity to cell
      cycle-dependent anticancer agents. To understand the molecular basis of drug
      resistance observed in brain tumors, we examined the relationship between
      alteration of p16, a cyclin dependent kinase inhibitor whose functions are
      frequently lost in many human gliomas, and chemosensitivity of tumor cells to
      various kinds of anticancer agents. Alterations of the p16 gene that include
      mutation(s) and homozygous deletion as well as p16 protein expression level, were
      examined in 56 specimens of astrocytic tumors. Their in vitro chemosensitivities
      to 30 kinds of anticancer agents were analyzed with flow cytometry which detects
      drug-induced cell death. We found that the alterations were correlated with
      increased sensitivity to antimetabolite anticancer agents but not with other
      kinds of agents, including alkylating agents, antibiotics, topoisomerase
      inhibitors and antimicrotubule agents. The present results suggest that p16 plays
      a role in determining chemosensitivity of brain tumors, depending on
      pharmacological mechanisms of anticancer agents. Proper understanding of the
      molecular machinery which regulates the chemosensitivity may contribute to the
      choice of anticancer agents for individual patients.

PMID- 10938391
TI  - Frequent chromosomal instability but no microsatellite instability in
      hepatocellular carcinomas.
AB  - Microsatellite instability (MSI) phenotype, caused by a deficiency of DNA
      mismatch repair genes, has been detected in a subset of tumors in the
      gastrointestinal tract. However, it is not clear how MSI is involved in the
      tumorigenesis of hepatocellular carcinomas (HCC). Results with HCC are
      controversial, with positive results published with American and European tumors,
      but negative with Japanese tumors. We report the absence of MSI in 39 Korean HCCs
      after analysis with 6 mononucleotide- and over 150 dinucleotide-repeat markers.
      Only one such dinucleotide-repeat (D2S213) exhibited a reproducible shift in
      mobility, representing a somatic mutation present in only some of the tumor
      cells. This may be the result of a spontaneous error of replication due to the
      intrinsic mutability of these unstable sequences and without any connection to
      true genomic instability. In support of this interpretation, no frameshift
      mutations were found at the coding repeats of target genes for the microsatellite
      mutator phenotype including TGF-betaRII, BAX, hMSH3, and hMSH6. In contrast, we
      observed frequent allelic losses on chromosomes 4q, 8p, 16q, and 17p by the
      analysis of dinucleotide repeats (microallelotyping), reflecting a high degree of
      tumor chromosomal instability, which was significantly associated to the tumor
      differentiation (p=0.036, Fisher's exact test). These results suggest that,
      unlike chromosomal instability, widespread MSI plays no role in the development
      or progression of HCC.

PMID- 10938392
TI  - CDDP induces p53-dependent apoptosis in tongue cancer cells.
AB  - We have investigated the CDDP sensitivities of two tongue cancer cell lines with
      differing p53 genetic status, one with wild-type p53 (SAS) and the other with
      mutant-type p53 (HSC-4). SAS was about 2 times more sensitive at the D10 dose and
      demonstrated increased p53 and Bax protein levels at 10 h after CDDP treatment on
      Western blot analysis. On the other hand, overexpression of p53 in HSC-4 was
      observed without CDDP treatment and no elevation of Bax could be detected.
      Apoptosis was observed after CDDP treatment in SAS but not in HSC-4 by Hoechst
      33342-staining and electrophoresis methods. These findings indicate that p53
      plays an important role in apoptosis as a positive regulator of Bax expression.
      It is suggested that p53 status may have predictive potential with regard to
      response to CDDP therapy.

PMID- 10938393
TI  - Gene expression of galectin-9/ecalectin, a potent eosinophil chemoattractant,
      and/or the insertional isoform in human colorectal carcinoma cell lines and
      detection of frame-shift mutations for protein sequence truncations in the second
      functional lectin domain.
AB  - The family of Ca2+-independent galactoside-binding lectins with the beta-strand
      topology of the jelly-roll, referred to as galectins, is known to mediate and
      modulate a variety of cellular activities. Their functional versatility explains
      the current interest in monitoring their expression in cancer research, so far
      primarily focused on galectin-1 and -3. Tandem-repeat-type galectin-9 and its
      (most probably) allelic variant ecalectin, a potent eosinophil chemoattractant,
      are known to be human leukocyte products. We show by RT-PCR with primers specific
      for both that their mRNA is expressed in 17 of 21 human colorectal cancer lines.
      As also indicated by restriction analysis, in addition to the expected transcript
      of 571 bp an otherwise identical isoform coding for a 32-amino acid extension of
      the link peptide was detected. Positive cell lines differentially expressed
      either one (7 lines) or both transcripts (10 lines). Sequence analysis of RT-PCR
      products, performed in four cases, allowed to assign the standard transcript to
      ecalectin in the case of SW480 cells and detected two point mutations in the
      insert of the link peptide-coding sequence in WiDr and Colo205. Furthermore, this
      analysis identified the insertion of a single nucleotide into the coding sequence
      generating a frame-shift mutation, an event which has so far not been reported
      for any galectin. This alteration encountered in both transcripts of the WiDr
      line and the isoform transcript of Colo205 cells will most likely truncate the
      protein part within the second (C-terminal) carbohydrate recognition domain. Our
      results thus reveal the presence of mRNA for a galectin-9-isoform or a potent
      eosinophil chemoattractant (ecalectin) or a truncated version thereof with
      preserved N-terminal carbohydrate recognition domain in established human colon
      cancer cell lines.

PMID- 10938394
TI  - Differential behavior of VEGF receptor expression and response to TNP-470 in two
      immortalized human endothelial cell lines.
AB  - Angiogenesis consists of endothelial cell proliferation, migration and tube
      formation. It is useful to investigate endothelial cell behavior using
      immortalized endothelial cell lines. We characterized cell growth property,
      growth factor dependency and response to angioinhibitory drugs; TNP-470,
      staurosporine, radicicol and genistein, using human umbilical vein endothelial
      cells (HUVECs) immortalized by human papilloma virus (HPV)-16 E6-E7, named
      HUVECs/E6-E7, and HUVECs/E6-E7 transformed by v-Ki-ras gene, named HUVECs/E6
      E7/ras. The dependency to vascular endothelial cell growth factor (VEGF) and
      basic fibroblast growth factor (bFGF) for cell proliferation decreased in
      HUVECs/E6-E7, but were restored in HUVECs/E6-E7/ras. Flow cytometric analysis
      demonstrated that a VEGF receptor KDR/flk-1 was down-regulated in HUVECs/E6-E7
      but not in HUVECs/E6-E7/ras. Expression of another VEGF receptor flt-1 was
      consistent in all cells including HUVECs, HUVECs/E6-E7 and HUVECs/E6-E7/ras.
      According to the analysis of the angioinhibitory drugs, HUVECs/E6-E7 was
      obviously resistant to TNP-470, but HUVECs/E6-E7/ras showed similar response
      compared to HUVECs which suggests that v-Ki-ras signaling pathway is associated
      with VEGF receptor expression and make HUVECs/E6-E7 sensitive to TNP-470 by
      modulating the signal transduction cascade. In conclusion, HPV-16 E6-E7 and v-Ki
      ras genes have unique growth properties and these immortalized cells are useful
      for investigating signal transduction pathways of endothelial cells, and for
      screening of angioinhibitory drugs.

PMID- 10938395
TI  - Not hMSH2 but hMLH1 is frequently silenced by hypermethylation in endometrial
      cancer but rarely silenced in pancreatic cancer with microsatellite instability.
AB  - Disruption of the DNA mismatch repair (MMR) system has been found to play an
      important role in sporadic human cancers of several organs such as colorectum,
      stomach, endometrium, and pancreas. In cancers of the former three organs,
      disruption of the MMR system is mainly caused by hypermethylation of the hMLH1
      gene. We investigated the expression of the hMLH1 and hMSH2 proteins
      immunohistochemically in pancreatic and endometrial cancers with high frequency
      microsatellite instability (MSI-H). Loss of expression of hMLH1 was found in none
      of seven pancreatic cancer, whereas eight (57%) of 14 endometrial cancer showed
      loss of expression of hMLH1. On the other hand, one (14%) of seven pancreatic
      cancers and two (14%) of 14 endometrial cancers showed loss of hMSH2 expression.
      We further analyzed the methylation status at the promoter region of the hMLH1
      and hMSH2 genes and found hypermethylation of hMLH1 at the promoter region in the
      great majority of endometrial cancers with loss of expression. However, no
      pancreatic cancer showed hypermethylation. We then further analyzed 22 pancreatic
      cancer cell lines and obtained similar results. These results suggested that MSI
      H in pancreatic cancer is probably caused by different mechanisms from those of
      other sporadic cancers with MSI-H.

PMID- 10938396
TI  - Phase II trial of cisplatin, 5-fluorouracil and folinic acid using a weekly 24-h
      infusion schedule for locally advanced head and neck cancer: a pharmacokinetic
      and clinical survey.
AB  - The objective of this phase II prospective study was to determine the efficacy
      and the toxicity of a new schedule of neoadjuvant chemotherapy in locally
      advanced squamous cell carcinomas of the head and neck (SCCHN). Thirty-three
      patients were included in this study (13 stage III and 20 stage IV). Cisplatin
      (CDDP: 35 mg/m2), 5-fluorouracil (FU: 2 g/m2) and folinic acid (FA: 500 mg/m2)
      were administered by continuous i.v. infusion for 24 h, once every 7 days. Six
      cycles of neoadjuvant chemotherapy were planned before definitive locoregional
      treatment. A total of 195 cycles were analysed for toxicity: mucositis was
      observed in 11/195 cycles; 12/195 showed diarrhea and vomiting occurred in
      10/195. The myelosuppression was low (neutropenia: 4/195, thrombopenia: 3/195).
      One treatment-related death was observed after grade IV neutropenia at the fourth
      cycle. Thirty-two patients were evaluated for response. The objective response
      rate was 87%, with 50% complete response (CR) and 37% partial response. Failure
      rate was 13% (stable disease). There was no progressive disease. Survival and DFS
      duration were significantly higher in cases of CR or in laryngeal localization.
      The average peak plasma levels for the 6 courses of CDDP, 5-FU, dl-FA and mTHF
      were 4.9+/-0.76 microM, 4.1+/-0.54 microM, 29.1+/-2.4 microM and 4.8+/-0.31
      microM respectively. Therefore, the administration of the 3 drugs by a 24 h
      continuous i.v. infusion reached an efficient level for drug modulation. This new
      weekly schedule is as active as other standard therapy in the disease but
      significantly less toxic as neoadjuvant chemotherapy in advanced untreated SCCHN.
      With the low toxicities observed with this schedule, additional treatment
      (surgery and/or radiotherapy) is warranted to evaluate the impact on overall
      survival of SCCHN.

PMID- 10938398
TI  - Binding of 125I after administration of 125I-EGF-dextran, 125I-EGF or 125I to
      human bladder cancer spheroids.
AB  - The binding of a targeting agent, 125I-EGF-dextran, to epidermal growth factor
      (EGF) receptors in tumour spheroids of a human bladder cancer cell line was
      studied. The accumulation of radioactivity was continuous up to at least 48 h in
      the peripheral cells of the spheroids, which in comparison with the binding
      pattern of 125I-EGF indicated that the cells had a limited capacity to degrade
      the EGF-dextran. The 125I-EGF-dextran was of two different sizes, 28 and 76 kDa,
      but this did not affect the binding patterns and the results were very similar.
      The EGF-dextran conjugates had qualities that are of interest for tumour
      targeting.

PMID- 10938397
TI  - Expression of transforming growth factor beta1 and its type II receptor in mouse
      colon tumors induced by azoxymethane.
AB  - Alterations in transforming growth factor beta1 (TGF-beta1) and its type II
      receptor (TbetaR-II) have been implicated in the pathogenesis of a variety of
      human cancers and animal tumor models. We postulated that TGF-beta1 and TbetaR-II
      alterations may also be involved in mouse colon tumorigenesis induced by the
      chemical carcinogen, azoxymethane (AOM). In the present study, normal colon
      tissues and AOM-induced colon tumors from SWR/J mice were analyzed for mutational
      changes in the TbetaR-II gene, and the expression and localization of TGF-beta1
      and TbetaR-II were examined by reverse transcription-polymerase chain reaction
      (RT-PCR) and immunohistochemisty. Direct DNA sequencing of the coding sequence of
      the TbetaR-II gene revealed no mutational changes in tumors induced by AOM when
      compared with the sequence from normal colon tissue. However, TGF-beta1 and
      TbetaR-II mRNA levels in tumor samples were increased 1.8-fold (p<0.01) and 1.3
      fold (p<0.01), respectively, when compared with control mouse colon tissue. The
      results of immunohistochemical analysis of TGF-beta1 and TbetaR-II were
      correlated with mRNA expression data. An increase in staining intensity of both
      TGF-beta and TbetaR-II were observed in colon tumors. These findings suggest that
      alterations in the expression of TGF-beta1 and TbetaR-II may be involved in the
      pathogenesis of colon tumors induced by AOM in mice.

PMID- 10938399
TI  - Induction of apoptosis by ursolic acid through activation of caspases and down
      regulation of c-IAPs in human prostate epithelial cells.
AB  - Previous results indicate that ursolic acid (UA), a pentacyclic triterpene acid,
      has strong cytotoxic activity and effectively induces growth arrest in a variety
      of systems. However, the molecular mechanisms underlying anti-tumorigenic or
      chemopreventive activities of UA are poorly understood. To further determine the
      mechanism of UA, we investigated the effects of UA on the growth of human
      prostate epithelial cells. Upon treatment with UA, a concentration-dependent
      inhibition of cell viability was observed and cells developed many of the
      hallmark features of apoptosis, including condensation of chromatin and DNA
      fragmentation. These apoptotic effects of UA were accompanied by proteolytic
      cleavage of specific target proteins such as PARP, beta-catenin and Rad51
      proteins suggesting the possible involvement of caspases. Western blotting and in
      vitro assay demonstrated that processing/activation of at least four caspases
      (caspase-1, -3, -8 and -9) accompanies the generation of UA-mediating apoptotic
      cell death. In addition to activation of caspases, the down-regulation of c-IAPs
      family proteins, which suppress the apoptotic death signaling by the direct
      inhibition of activated caspases, was also observed. However, UA did not affect
      both the level of p53 expression and the alteration of the balance between Bcl-2
      and Bax expression. These data suggest that apoptotic signals evoked by UA
      treatment may converge caspases activation through down-regulation of c-IAPs
      family and without mitochondrial dysfunction.

PMID- 10938400
TI  - Peripheral blood tumor cell load reflects the clinical activity of the disease in
      patients with carcinoma of the breast.
AB  - Peripheral blood was examined for the presence of tumor cells at multiple time
      points over a one-year period in 45 patients with a history of surgical resection
      of breast carcinoma. The number of circulating epithelial cells in 8 of 8
      patients with clinically active disease concurred or preceded changes in the
      disease activity. In 12 of 37 patients with no evidence of disease epithelial
      cells were found at least at one time point at a frequency larger than the
      control group. One patient had a recurrence of the breast cancer 4 weeks after
      circulating epithelial cells were detected in the blood.

PMID- 10938402
TI  - Stabilization of disease as an indicator of clinical benefit associated with
      chemotherapy in non-small cell lung cancer patients.
AB  - In Phase II oncology studies, response rate has traditionally been used to assess
      activity. However stabilization of disease (SD) may also provide patient benefit.
      To assess the value of SD (stabilization of measurable disease for at least 8
      weeks) as a predictor of survival following chemotherapy in patients with non
      small cell lung cancer (NSCLC), we have analyzed data from 198 NSCLC patients
      receiving topotecan i.v. or orally as first-line therapy either as single agent
      or in combination. Proportional hazards (Cox) regression models showed that
      responders [complete response (CR) + partial response (PR), 1.5% and 11.6%
      respectively] had an estimated risk of death that was 9.8% (95% CI: 4.2% to
      22.7%) of that for progressive disease (PD) (60.1% of the patient population).
      Similarly, patients with SD (26.8% of the patient population) showed a potential
      benefit with a risk of death that was 27.7% of the one of patients with PD (95%
      CI: 17.8% to 43.1%). In conclusion SD may be a useful indicator of patient
      benefit from chemotherapy for NSCLC.

PMID- 10938401
TI  - Altered activity of MDR-reversing agents on KB3-1 cells transfected with Gly(185)
      ->Val human P-glycoprotein.
AB  - P-glycoprotein (P-gp) is a transmembrane glycoprotein that confers multidrug
      resistance (MDR). It has been demonstrated that the Gly185 residue within the
      cytoplasmic loop between predicted transmembrane portions 2 and 3 plays an
      important role in substrate specificity of human P-gp. Derivatives of cyclosporin
      interact with and reverse the ability of P-gp to act as a drug efflux pump. To
      determine if the Gly185 residue of human P-gp is also important for the
      interaction of P-gp with closely related cyclosporin derivatives, we examined the
      effect of PSC-833 and CsA on P-gp in KB3-1 cells transfected with human wild-type
      P-gp (GSV-2) or with the mutant P-gp (VSV-1) that habored the Gly185-->Val
      substitution. While the ability of CsA to sensitize VSV-1 cells to anticancer
      agents was enhanced, no changes in the potency of PSC-833 against cells
      transfected with either the wild-type or mutant P-gp were observed. In addition,
      VSV-1 transfected cells were more sensitive to CsA inhibition of verapamil
      stimulated ATPase activity than cells transfected with wild-type P-gp.
      Furthermore, the intracellular accumulation of CsA was low in GSV-2 P-gp
      expressing cells, compared with its accumulation in VSV-1 cells and it was found
      to be as high as in non-P-gp expressing KB3-1 cells. These results indicated an
      enhanced sensitivity of Val185-P-gp expressing cells to CsA that correlated with
      increased intracellular accumulation in these cells. In contrast, no significant
      difference in the accumulation of PSC-833 was observed among the parental, wild
      type or resistant cells. Since PSC-833 was found to be more potent than CsA,
      these studies provided insight into the effects of the structure of MDR
      modulators in mediating sensitivity to anticancer drugs.

PMID- 10938403
TI  - Serum ICAM-1 concentrations following conventional dose consolidation
      chemotherapy for acute myeloid leukemia and after high dose chemotherapy with
      autologous haematopoietic stem cell rescue.
AB  - Serum concentrations of soluble ICAM-1 (sICAM-1) were studied in patients with
      acute myeloid leukemia (AML) after conventional dose consolidation chemotherapy
      and in AML and in breast cancer patients following high dose chemotherapy with
      autologous haematopoietic stem cell transplantation. Investigations were carried
      out at 3 phases following treatment; during the chemotherapy induced neutropenic
      phase (neutrophil counts <0.5x109/l); during early recovery (neutrophil counts
      0.5x109/l-1.0x109/l); and at recovery from neutropenia (neutrophil count
      1.0x109/l-2.5x109/l). Results showed a significant elevation of serum levels of
      sICAM-1, above normal, in both groups of patients during the neutropenic phase. A
      further increase of sICAM-1 was found in conventional dose consolidation
      chemotherapy treated AML patients during the post-neutropenia recovery phases. By
      contrast, patients who were treated with high dose chemotherapy plus autologous
      haematopoietic stem cell transplantation showed a normalisation of sICAM-1
      concentration during the post-neutropenic recovery phases. These findings suggest
      that recovery of neutrophil function do not coincide with recovery of neutrophil
      count following intensive chemotherapy while rapid recovery of neutrophil
      function occurred among patients who received autologous haematopoietic stem cell
      support.

PMID- 10938404
TI  - Expression of CD11b/CD18 on neutrophils after consolidation chemotherapy for
      acute myeloid leukemia and after high dose chemotherapy with autologous
      haematopoietic stem cell transplantation.
AB  - Quantitative expression of neutrophil CD11b/CD18 following chemotherapy (either
      conventional dose consolidation chemotherapy or high dose chemotherapy with
      autologous stem cell transplantation) was investigated during the early recovery
      phase (neutrophil count 0. 5-1.0x109/l) and at full recovery (neutrophil count
      1.0-2.5x109/l) following treatment. CD11b/18 expression was normal in stem cell
      transplantation supported patients during both early and full neutrophil
      recovery. By contrast CD11b/CD18 expression was markedly decreased in patients
      who received chemotherapy without stem cell support. These results suggest that
      recovery of neutrophil count may not always coincide with recovery of neutrophil
      function and that G-CSF stimulated peripheral stem cell transplantation enhances
      neutrophil function post chemotherapy.

PMID- 10938405
TI  - Spontaneous apoptosis of Reed-Sternberg and Hodgkin cells; clinical and
      pathological implications in patients with Hodgkin's disease.
AB  - The experiments were designed to study correlation between frequency of apoptosis
      of Reed-Sternberg/Hodgkin (R-S/H) cells, EBV infection of these cells, expression
      of the key proteins involved in regulation of apoptosis and cell cycle in R-S/H
      cells, the patients' pretreatment markers and the clinical outcome. One hundred
      and ten Hodgkin's disease (HD) patients were studies, of which 69 obtained
      complete remission (CR) after first-line treatment and 41 did not respond. The
      time of follow-up was from 18 to 242, median 69.7, months. Apoptosis was
      evaluated by TUNEL technique (TdT-mediated dUTP nick end labeling) and the
      presence of EBV-latent membrane protein 1 as well as expression of Bcl-2, tumor
      suppressor p53, p21WAF1, MDM-2, Rb1, PCNA, p27KIP1 and caspase-3, was detected
      immunocytochemically on paraffin-embedded lymph node specimens obtained at
      diagnosis. Positive TUNEL reaction was found in 43 patients with apoptotic index
      (AI) in this group varying between 10% and 60%. In the remaining 57 patients AI
      of R-S/H cells was below 10%. In 62 patients the cells surrounding R-S/H cells
      were also TUNEL-positive; their frequency was variable. The expression of LMP1
      protein on R-S/H cells was found in 38 patients, without any correlation with the
      presence or frequency of apoptosis. No significant difference was seen between
      the AI and both clinical stage and histological type of the disease. However, the
      mean AI in non-responding patients was significantly higher than in CR group
      (p=0.015); the high frequency of apoptosis was also negatively correlated with
      the progression free survival time (p=0.031) and the overall survival (p=0.042).
      The expression of PCNA, p21WAF1, p53 protein and caspase-3 also showed positive
      correlation with frequency of apoptosis (p=0.011, p=0.036, and p=0.001,
      respectively). On the other hand, no statistically confirmed correlation was
      found between AI and expression of bcl-2, MDM-2, Rb1, and p27KIP1 on R-S/H cells.
      These data provide evidence that tumor cells in HD undergo spontaneous apoptosis
      regardless of EBV infection. High pretreatment AI correlates with poor response
      to the treatment, and may be considered as a potential negative prognostic factor
      in HD.

PMID- 10938406
TI  - Changes in renal autacoids and hemodynamics associated with aging and isolated
      systolic hypertension.
AB  - The aging kidney is characterized by a decrease in renal blood flow and
      glomerular filtration rate mainly due to glomerulosclerosis. Nevertheless, even
      in the presence of these changes, the kidney maintains its functionality until
      advanced age. However, there is a tendency towards greater renal vasoconstriction
      in the elderly as compared with young individuals. This occurs either in
      physiological circumstances such as physical exercise, or in disease
      manifestations, such as the effective circulatory volume depletion that develops,
      for example, in heart failure. This tendency may be secondary to the reduction of
      renal autacoid modulatory capacity, particularly at the vasodilating
      prostaglandin level. In an acute experimental model we could demonstrate that, in
      the healthy elderly, the renal response to adrenergic activation by mental stress
      is characterized by a prolonged and pronounced vasoconstriction. In addition to
      this, in elderly patients affected by isolated systolic hypertension, we
      demonstrated an impairment of renal hemodynamic and humoral adaptation capacity
      in response to adrenergic activation and blood pressure increase. In the presence
      of sudden blood pressure increase, the kidney of these patients responds with a
      passive vasodilation and a glomerular filtration rate increase without any
      activation of humoral modulatory substances. The impairment in renal adaptation
      capacity may predispose these patients to renal injury, particularly in the
      presence of the many hypertensive peaks which characterize everyday life of
      elderly individuals. In conclusion, these results show that renal adaptation
      capacity of elderly patients with isolated systolic hypertension is completely
      lost. Further studies will elucidate whether antihypertensive treatment per se,
      or specific classes of antihypertensive drugs, are able to revert this
      impairment.

PMID- 10938407
TI  - Troglitazone has a reducing effect on thromboxane production.
AB  - Effects of troglitazone, an antidiabetic thiazolidinedione that enhances insulin
      sensitivity, on thromboxane (TX) production were assessed in human
      erythroleukemia (HEL) cells and human platelets. Measurement of TX was performed
      by using the gas chromatography/selected ion monitoring (GC/SIM) method. We found
      that troglitazone reduced the TX production from HEL cells and human platelets.
      Furthermore, troglitazone also reduced arachidonic acid (AA)-induced TX
      production from HEL cell and thrombin-induced TX release from platelets. In
      addition, we compared the effect of troglitazone with that of alpha-tocopherol
      and BRL 49653. Other thiazolidinedione compound BRL 49653 had effects similar to
      troglitazone, but alpha-tocopherol had no effect on TX production. Our findings
      suggest that the thiazolidinedione group had an antithrombotic effect and was
      beneficial in preventing vascular complications often observed in diabetes
      mellitus.

PMID- 10938408
TI  - Cellular distribution of prostanoid EP receptors mRNA in the rat gastrointestinal
      tract.
AB  - The inhibition of PGE(2) synthesis resulting from sustained NSAIDs therapy has
      been linked to gastrointestinal irritations and ulceration. The multiple
      physiological effects of PGE(2) in the gut are mediated through the activation of
      four receptors termed EP(1-4). The aim of the study was to determine the precise
      distribution of the four prostaglandin E(2) receptors in the rat stomach, small
      intestine, and colon. We used non-radioactive in situ hybridization techniques on
      paraffin-embedded tissue. Mucous cells of the stomach and goblet cells of the
      small intestine and colon were found to express mRNA for all four EP subtypes. A
      positive hybridization signal for EP(1), EP(3), and EP(4) was detected in the
      parietal cells of the stomach whereas the chief cells expressed low levels of
      EP(1) and EP(3). The EP(1) and EP(3) receptor mRNA could also be detected in the
      muscularis mucosa, longitudinal muscle and enteric ganglias of the stomach and
      small intestine. However, close examination of the enteric ganglias indicated
      that most of the positive labeling was localized to the glial cells, although
      some neurons did express EP(3). In conclusion, we have detailed the distribution
      of prostanoid EP receptors in the gut at the cellular level, giving new insights
      to the role of prostaglandins in gastrointestinal functions.

PMID- 10938409
TI  - Epigallocatechin gallate increase the prostacyclin production of bovine aortic
      endothelial cells.
AB  - We describe the effect of (-) epigallocatechin gallate (EGCg), one of catechins
      known in tea, on the prostacyclin (PGI) production by bovine aortic endothelial
      cells. The amounts of 6-keto-PGF(1alpha) and Delta(17)-6-keto-PGF(1alpha), stable
      metabolites of PGI(2) and PGI(3), released in culture medium were measured using
      gas chromatography/selected ion monitoring (GC/SIM). The prostacyclin production
      of endothelial cells was increased by EGCg in a dose- and time-dependent manner.
      The effect by EGCg was stronger than any other catechins (catechin, epicatechin,
      epigallocatechin, and epicatechin gallate). When endothelial cells incubated with
      EGCg and arachidonic acid (AA) or eicosapentaenoic acid (EPA), PGI(2), and PGI(3)
      production were increased greater than those incubated with AA or EPA alone.
      Furthermore, gallic acid, that also has a pyrogallol structure, increased PGI(2)
      production. These observations indicate that catechins increase the prostacyclin
      production and that the pyrogallol structure is significant to this function.

PMID- 10938410
TI  - Induction of PGHS-2 mRNA in response to cerebral hypoperfusion in late-gestation
      fetal sheep.
AB  - Previous studies have demonstrated that cerebral ischemia stimulated the
      increased abundance of immunoreactive PGHS-2, but not PGHS-1, in brain tissue
      homogenates in late-gestation fetal sheep. The goal of the present study was to
      detect PGHS-1 and PGHS-2 mRNA in specific fetal brain regions, and to semi
      quantitatively detect changes in the abundance of the respective mRNA's in
      response to cerebral hypoperfusion. Fetal brain tissues were collected from
      control fetuses and from fetuses 30 min and 2 h after cerebral hypoperfusion
      (produced by brachiocephalic occlusion). Messenger RNA was studied by RT-PCR, and
      expressed semiquantitatively as a ratio of PGHS-1 or PGHS-2 mRNA abundance to
      beta-actin mRNA abundance. PGHS-2 mRNA was only detected in the fetal
      hippocampus, hypothalamus, and brain stem and it was induced by cerebral
      hypoperfusion. In contrast, PGHS-1 mRNA was detected in all fetal brain tissues
      but was not induced. We conclude that cerebral hypoperfusion induced PGHS-2 gene
      expression in hippocampus, hypothalamus, and brainstem, and we speculate that the
      increased abundance of the enzyme is likely to be important for control of reflex
      responses to hypotension in the fetus.

PMID- 10938411
TI  - Determination of urinary 8-epi-prostaglandin F(2alpha) using liquid
      chromatography-tandem mass spectrometry: increased excretion in diabetics.
AB  - Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the
      quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi
      PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi
      PGF(2alpha), were extracted from urine by using a solid phase extraction
      cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The
      standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0. 997).
      The accuracy of the added 8-epi-PGF(2alpha) ranged from 96.8 to 104.9% with a
      mean +/- SD of 99.5+/-2.5%. The average level +/- SD of urinary 8-epi-PGF(2alpha)
      in 13 healthy volunteers (five women and eight men, 31+/-7.4 years old) was
      429.4+/-149.6 pg/mg creatinine. The level of seven patients with noninsulin
      dependent diabetes mellitus (two women and five men, 40+/-13.6 years old),
      630.9+/-275.6 pg/mg creatinine, was statistically higher than that of healthy
      volunteers (P<0.05). This finding suggested that diabetics are in a highly
      oxidative condition. This simple and rapid LC/MS-MS method can be used to
      elucidate the pathophysiological feature of diabetes or for monitoring the
      curative effect.

PMID- 10938413
TI  - Uptake of reactive textile dyes by Aspergillus foetidus.
AB  - An isolated fungus, Aspergillus foetidus was found to effectively decolorize
      media containing azo reactive dyes namely, Drimarene dyes. The extent of color
      removal was greater than 95% within 48 h of growth of the fungus. The entire
      color was found to be strongly bioadsorbed to the rapidly settling fungal biomass
      pellets without undergoing significant biotransformation. Our investigations
      reveal that the process of decolorization is concomitant with the exponential
      growth phase of the fungus and has requirement for a biodegradable substrate such
      as glucose. The fungus was also able to decolorize media containing mixture of
      dyes to an extent of 85% within 72 h of growth. Kinetic analyses of fungal
      decolorization indicate that the process is time dependent and follows first
      order kinetics with respect to initial concentration of dye. The rates of color
      uptake (k values) decrease to a significant extent with increasing initial
      concentrations of dye. The fungus was able to grow and decolorize media in the
      presence of 5 ppm of chromium and 1% sodium chloride. An alternate and cheaper
      carbon source such as starch supported the growth and decolorization process.
      These results suggest that dye uptake process mediated by A. foetidus has a
      potential for large-scale treatment of textile mill discharges.

PMID- 10938412
TI  - Oxidized low-density lipoprotein (LDL) enhances thromboxane A(2) synthesis by
      platelets, but lysolecithin as a product of LDL oxidation has an inhibitory
      effect.
AB  - Oxidation of low-density lipoprotein (LDL) by copper sulfate led to a significant
      increase in lysophosphatidylcholine (lyso PC) at the expense of
      phosphatidylcholine. Incubation of different concentrations of oxidized LDL
      (oxLDL) (32-650 microg protein/ml) with platelets for 1 h at 37 degrees C
      increased lyso PC content. The increase was dependent on oxLDL concentration.
      Incubation of platelets with various concentrations of lyso PC in solution for 5
      or 15 min showed that lyso PC percentage was increased in the platelet membrane
      and the increase was dose dependent. Platelets incubated with various
      concentrations of lyso PC (2-100 microM) for 5 or 15 min and then triggered with
      thrombin also showed a significant decrease of thromboxane A(2) (TXA(2)) release
      as lyso PC concentration reached 10 microM or 6 microM, respectively. The
      decrease of TXA(2) release was more significant as lyso PC concentration was
      increased. The present study showed that this inhibition of TXA(2) release by
      lyso PC was due to 1) inhibition of phospholipase A(2) and the decrease of free
      arachidonic acid liberation from platelet phospholipid and 2) inhibition of
      cyclooxygenase. These inhibitory effects of lyso PC were discussed in relation to
      its effect on membrane fluidity. Lyso PC at concentrations of 30, 50, and 100
      microM caused a sudden drop in TXA(2) release and a sudden increase of lactic
      dehydrogenase loss from the platelets due to their lysis and inhibition of
      cyclooxygenase enzyme. The present study shows that oxLDL contains high levels of
      lyso PC that are transferable to the platelets and can weaken their
      responsiveness to thrombin and decrease TXA(2) release. In our previous study, we
      found that oxLDL also contained high levels of oxysterols and thiobarbituric acid
      reactive substances (TBARS), which enhanced platelet reactivity to thrombin and
      increased TXA(2) release. We conclude that the net effect of oxLDL on platelets
      will depend on its degree of oxidation and the ratio between oxysterols plus
      TBARS/lyso PC. Variations in this ratio may explain some of the contradictions
      cited in the literature concerning the effect of oxLDL on platelet activation.

PMID- 10938414
TI  - Preparation and properties of immobilized amyloglucosidase on nonporous PS/PNaSS
      microspheres.
AB  - Nonporous polystyrene/poly(sodium styrene sulfonate) (PS/PNaSS) microspheres were
      used for immobilization of amyloglucosidase and the properties of immobilized
      enzyme was studied and compared with those of free enzyme. Sulfonated groups on
      the PS/PNaSS microspheres present a very simple, mild, and time-saving process
      for enzyme immobilization. Nonporous microspheres provide their surface for
      immobilization of enzyme and prevent the diffusion limitation problem in the
      pore. Despite the high concentration of bound enzyme the influence of
      immobilization on kinematic parameters, K(m) and V(max), is relatively low
      compare to other porous supports. Simple and time-saving immobilization procedure
      as well as the effects of pH and temperature on immobilized enzyme also showed
      that the PS/PNaSS microspheres could be good support.

PMID- 10938415
TI  - Production of alcohol from raw wheat flour by Amyloglucosidase and Saccharomyces
      cerevisiae.
AB  - Ethanol production, by a simultaneous saccharification and fermentation process
      from raw wheat flour, has been performed by Saccharomyces cerevisiae and a low
      level of amyloglucosidase enzyme. The fermentation time was about 60 h after a 6
      h pre-saccharification, with an amyloglucosidase (AMG) level of 270 AGU. kg(-1)
      starch, but only 31 h with a simultaneous saccharification fermentation process
      (SSF). When an AMG level of 540 AGU. kg(-1) starch was used, the time decreased
      to 21 h, giving an ethanol concentration of 67 g. l(-1). Sugar composition of the
      wort after the liquefaction may be responsible of the difference between these
      two process. Maltose, a fermentable sugar, was produced in high concentration
      during the liquefaction, allowing a shorter process period, counteracting the
      effect of the slow starch hydrolysis at 35 degrees C (SSF temperature).

PMID- 10938416
TI  - Enzymatic acetylation of 10-deacetylbaccatin III to baccatin III by C-10
      deacetylase from Nocardioides luteus SC 13913.
AB  - Baccatin III is a polycyclic diterpene which can be used for the semi-synthesis
      of paclitaxel and analogs. An enzymatic process was developed for the conversion
      of 10-deacetylbaccatin III (10-DAB) to baccatin III without requiring protection
      of the 7-hydroxyl group. A C-10 deacetylase from Nocardioides luteus SC 13912 was
      immobilized on diethylaminoethyl cellulose (DEAE-Cellulose) and the immobilized
      enzyme was used in the biotransformation process. The reaction was catalyzed
      using vinyl acetate as acyl donor at ambient temperature and at pH 7. A reaction
      yield of 51% was obtained.

PMID- 10938417
TI  - Biocatalytic preparation of a chiral synthon for a vasopeptidase inhibitor:
      enzymatic conversion of N(2)-
AB  - [4S-(4I,7I,10aJ)]1-Octahydro-5-oxo-4-[phenylmethoxy)carbonyl]amino]-7H-pyrido
      [2,1-b] [1,3]thiazepine-7-carboxylic acid methyl ester (BMS-199541-01) is a key
      chiral intermediate for the synthesis of Omapatrilat (BMS-186716), a new
      vasopeptidease inhibitor under development. By using a selective enrichment
      culture technique we have isolated a strain of Sphingomonas paucimobilis SC
      16113, which contains a novel L-lysine epsilon-aminotransferase. This enzyme
      catalyzed the oxidation of the epsilon-amino group of lysine in the dipeptide
      dimer N(2)-[N[phenyl-methoxy)-carbonyl] L-homocysteinyl] L-lysine)1,1-disulphide
      (BMS-201391-01) to produce BMS-199541-01. The aminotransferase reaction required
      alpha-ketoglutarate as the amino acceptor. Glutamate formed during this reaction
      was recycled back to alpha-ketoglutarate by glutamate oxidase from Streptomyces
      noursei SC 6007. Fermentation processes were developed for growth of S.
      paucimobilis SC 16113 and S. noursei SC 6007 for the production of L-lysine
      epsilon-amino transferase and glutamate oxidase, respectively. L-lysine epsilon
      aminotransferase was purified to homogeneity and N-terminal and internal peptides
      sequences of the purified protein were determined. The mol wt of L-lysine epsilon
      aminotransferase is 81 000 Da and subunit size is 40 000 Da. L-lysine epsilon
      aminotransferase gene (lat gene) from S. paucimobilis SC 16113 was cloned and
      overexpressed in Escherichia coli. Glutamate oxidase was purified to homogeneity
      from S. noursei SC 6003. The mol wt of glutamate oxidase is 125 000 Da and
      subunit size is 60 000 Da. The glutamate oxiadase gene from S. noursei SC 6003
      was cloned and expressed in Streptomyces lividans. The biotransformation process
      was developed for the conversion of BMS-201391-01 to BMS-199541-01 by using L
      lysine epsilon-aminotransferase expressed in E. coli. In the biotransformation
      process, for conversion of BMS-201391-01 (CBZ protecting group) to BMS-199541-01,
      a reaction yield of 65-70 M% was obtained depending upon reaction conditions used
      in the process. Phenylacetyl or phenoxyacetyl protected analogues of BMS-201391
      01 also served as substrates for L-lysine epsilon-aminotransferase giving
      reaction yields of 70 M% for the corresponding BMS-199541-01 analogs. Two other
      dipeptides N-[N[(phenylmethoxy)carbonyl]-L-methionyl]-L-lysine (BMS-203528) and
      N,2-[S-acetyl-N-[(phenylmethoxy)carbonyl]-L-homocysteinyl]-L-lysine (BMS-204556)
      were also substrates for L-lysine epsilon-aminotransferase. N-alpha-protected
      (CBZ or BOC)-L-lysine were also oxidized by L-lysine epsilon-aminotransferase.

PMID- 10938418
TI  - Influence of dissolved oxygen tension and agitation speed on alginate production
      and its molecular weight in cultures of Azotobacter vinelandii*
AB  - The alginate production by Azotobacter vinelandii, as well as the molecular
      weight of the polymer, are strongly influenced by the dissolved oxygen tension
      (DOT) and stirring speed of the culture. Under high DOT (5% of air saturation),
      the bacteria produced more alginate (4.5 g/l) than that obtained at low (0.5%)
      oxygen tension (1.0 g/l) in cultures conducted at 300 rpm. On the other hand,
      under constant DOT (3%), the higher the stirring speed (from 300 to 700
      rev./min), the higher the specific growth rate and the alginate production rate.
      However, low agitation speed (300 rev./min) lead the culture to produce a polymer
      of high molecular weight (680 000 g/g mol) whereas a low molecular weight (352
      000 g/g mol) alginate was isolated from cultures conducted at high (700 rev./min)
      stirring speed. At 700 rev./min, the MMW increased to a plateau between 1 and 3%
      DOT and then decreased to a minimum of 0.11 x 10(6) g/g mol at 7%. Microscopic
      observations revealed the presence of cell aggregates (one order of magnitude
      larger than individual cells) when the culture was conducted at 300 rev./min.
      Oxygen gradients occurring within the aggregates could be responsible of this
      phenomenon. At high agitation rate, the MMW of the alginate dropped towards the
      end of the culture in all conditions evaluated. Alginase activity was detected,
      which would be responsible for this phenomenon.

PMID- 10938419
TI  - Purification and characterization of the 1-3-propanediol dehydrogenase of
      Clostridium butyricum E5.
AB  - 1-3 PPD dehydrogenase (EC 1.1.1.202) was purified to homogeneity from Clostridium
      butyricum E5 grown anaerobically on glycerol in continuous culture. The native
      enzyme was estimated by gel filtration to have a molecular weight of 384 200 +/-
      31 100 Da; it is predicted to exist as an octamer or a decamer of identical
      molecular weight subunits. When tested as a dehydrogenase, the enzyme was most
      active with 1-3 propane diol. In the physiological direction, 3
      hydroxypropionaldehyde was the preferred substrate. The apparent K(m) values of
      the enzyme for 3-hydroxypropionaldehyde and NADH were 0.17 mM and 0.06 mM,
      respectively. The enzyme requires only Mn(2+) for full activity. The enzyme was
      found to have properties similar to those reported for Klebsellia pneumoniae,
      Citrobacter freundii, and Clostridium pasteurianum.

PMID- 10938420
TI  - Purification and characterization of an extracellular alpha-amylase produced by
      Lactobacillus manihotivorans LMG 18010(T), an amylolytic lactic acid bacterium.
AB  - This work presents the purification and characterization of an extracellular
      alpha-amylase (1,4-alpha-D-glucan glucanohydrolase, EC 3.2.1.1) produced by a new
      lactic acid bacterium: Lactobacillus manihotivorans able to produce L(+) lactic
      acid from starch. The molecular weight was found to be 135 kDa. The temperature
      and pH optimum were 55 degrees C and 5.5, respectively, and pI was 3.8. The alpha
      amylase had good stability at pH range from 5 to 6 and the enzyme was sensitive
      to temperature, losing activity within 1 h of incubation at 55 degrees C. Higher
      thermal stability was observed when the enzyme was incubated in presence of
      soluble starch. K(m) value and activation energy were 3.44 mg/ml and 32.55
      kJ/mol, respectively. Amylose was found to be a better substrate than soluble
      starch and amylopectin. Al(3+), Fe(3+), and Hg(2+) (10 mM) almost completely
      inhibited the alpha-amylase.

PMID- 10938421
TI  - Optimisation of culture medium and conditions for alpha-l-Arabinofuranosidase
      production by the extreme thermophilic eubacterium Rhodothermus marinus.
AB  - The culture medium for Rhodothermus marinus was optimised on a shake-flask scale
      by using statistical factorial designs for enhanced production of a highly
      thermostable alpha-L-arabinofuranosidase (AFase). The medium containing 3.6 g/l
      birch wood xylan and 8.2 g/l yeast extract yielded a maximum of 110 nkat/ml AFase
      activity together with 125 nkat/ml xylanase and 65 nkat/ml beta-xylosidase
      activity. In addition, low levels of beta-mannanase (30 nkat/ml), alpha
      galactosidase (0.2 nkat/ml), beta-galactosidase (0.3 nkat/ml), endoglucanase (5
      nkat/ml) and beta-glucosidase (30 nkat/ml) were detected in the culture filtrate.
      Among the various carbon sources tested, birchwood xylan was most effective for
      the formation of AFase and xylanase activities, followed by oat spelt and
      beechwood xylans, and xylan-rich lignocelluoses (e.g., starch-free sugar beet
      pulp and wheat bran). Constitutive levels of enzyme activities were detected when
      the bacterium was grown on other polysaccharides and low-molecular-weight
      carbohydrates. A fermentation in a 5-l fermenter (3-l working volume) using the
      optimised medium yielded 60 nkat/ml AFase associated with 65 nkat/ml xylanase and
      35 nkat/ml beta-xylosidase activities. The crude AFase displayed optimal activity
      between pH 5.5 and 7 and at 85 degrees C. It had half-lives of 8.3 h at 85
      degrees C and 17 min at 90 degrees C. It showed high stability between pH 5 and 9
      (24 h at 65 degrees C). The combined use of AFase-rich xylanase and mannanase
      from R. marinus in the prebleaching of softwood kraft pulp gave a brightness
      increase of 1.8% ISO. To our knowledge, this is the first report on the
      production of a high AFase activity by an extreme thermophilic bacterium and this
      enzyme is the most thermostable AFase reported so far.

PMID- 10938422
TI  - Estimation of kinetic parameters by progress curve analysis for the synthesis of
      (R)-mandelonitrile by Prunus amygdalus hydroxynitrile lyase.
AB  - Consistent sets of kinetic parameters were estimated for the synthesis of (R)
      mandelonitrile, catalyzed by Prunus amygdalus hydroxynitrile lyase, at 5 and 25
      degrees C and pH 5.5 by progress curve analysis. The rate constants and
      equilibrium constants of the nonenzymatic reaction were determined separately to
      reduce the number of parameters to be estimated simultaneously. At a lower
      temperature the equilibrium is much more favorable and the formation of rac
      mandelonitrile by the nonenzymatic reaction is suppressed. The estimated kinetic
      parameters were used to identify that the rate determining step in the catalytic
      cycle is the release of (R)-mandelonitrile from the ternary complex.

PMID- 10938423
TI  - Exploitation of a cellulose-binding domain from Neurospora crassa.
AB  - After eight decades as a purely research organism, Neurospora crassa is becoming
      a production system for heterologous peptides. The present work exploits the cbh
      1 gene, which encodes a class C cellobiohydrolase (EC 3.2.1.91) and has, at its
      carboxy-terminus, a domain with homology to other fungal cellulose-binding
      domains. We describe the construction of two translational fusions of the
      putative cellulose-binding domain with a reporter gene, which is the catalytic
      domain of the gla-1 glucoamylase gene of the same species, their transformation
      back into the organism, and expression of the constructs as cellulose-binding
      glucoamylase activity. This adds to the developing biotechnology of the organism
      the potential for enzyme/protein immobilisation.

PMID- 10938424
TI  - Concentrates of DHA from fish oil by selective esterification of cholesterol by
      immobilized isoforms of lipase from Candida rugosa.
AB  - Two lipases (Lip A and Lip B), were purified from a commercial lipase preparation
      produced by Candida rugosa and partially characterized. The purified lipases were
      immobilized on Duolite A 568 and used in the selective esterification of
      cholesterol with free fatty acids from sardine fish oil. The results showed that
      Lip A and Lip B preferentially esterified saturated and monounsaturated fatty
      acids allowing a 3.4-fold (Lip B, 24 h) and 4-fold (Lip A, 10 h) enrichment of
      docosahexaenoic acid in the remaining free fatty acid fraction. Selectivity
      towards eicosapentaenoic acid was less pronounced. By this selective
      esterification docosahexaenoic acid was concentrated from 7.4 to 32% with a
      recovery of 95% of its initial content in sardine fish oil.

PMID- 10938425
TI  - Substantia nigra dopamine regulates synaptic plasticity and membrane potential
      fluctuations in the rat neostriatum, in vivo.
AB  - The spiny projection neurons of the neostriatum are a site at which dopamine
      inputs from the substantia nigra converge with excitatory inputs from the
      cerebral cortex. These two systems interact in certain learning and motor control
      mechanisms of the brain. We investigated these interactions using intracellular
      recording from spiny striatal neurons in urethane-anaesthetized rats. We found
      that acute dopamine depletion was associated with long-term depression of
      corticostriatal synaptic input. Electrical stimulation of the cortex which
      mimicked synchronous cortical input to striatal neurons also induced long-term
      depression of corticostriatal inputs. In intact control animals, but not in
      dopamine-depleted animals, this depression was prevented or reversed by
      concomitant stimulation of the substantia nigra. In agreement with previous in
      vitro studies, our in vivo findings show that long-term depression occurs in the
      corticostriatal pathway, and in addition show that it is regulated by
      dopaminergic inputs from the substantia nigra. This form of synaptic plasticity
      may therefore be important for understanding disturbances of the motor system
      seen in humans with Parkinson's disease.

PMID- 10938426
TI  - Expression of the neuronal calcium sensor protein family in the rat brain.
AB  - The neuronal calcium sensor proteins are members of the calcium-binding protein
      superfamily. They control localized calcium signalling on membranes and may make
      G-protein cascades sensitive to cytosolic calcium. The family members are
      recoverin (visinin, S-modulin), neuronal calcium sensor-1 (frequenin),
      hippocalcin, neuronal visinin-like protein-1 (visinin-like protein, neurocalcin
      alpha), neuronal visinin-like protein-2 and neuronal visinin-like protein-3.
      Recoverin is expressed only in the retina and pineal gland. Using in situ
      hybridization, we mapped the expression of the other neuronal calcium sensor
      protein genes in the adult rat brain. Neuronal visinin-like protein-1 messenger
      RNA has a widespread distribution and is abundant in all brain areas except the
      caudate-putamen. Neuronal calcium sensor-1 gene expression is pan-neuronal.
      Neuronal calcium sensor-1 messenger RNA is present in the dendrites of
      hippocampal pyramidal and granule cells, suggesting a specific role in dendritic
      function. Hippocalcin and neuronal visinin-like protein-2 are mainly expressed in
      the forebrain and have similar expression patterns (neocortex, hippocampus and
      caudate-putamen). Neuronal visinin-like protein-3 has the most restricted
      expression; its highest expression level is in the cerebellum (Purkinje and
      granule cells). However, the neuronal visinin-like protein-3 gene is also
      expressed in many ventral nuclei throughout the fore- and midbrain, in the medial
      habenulae, and in the superior and inferior colliculi. The neuronal calcium
      sensor proteins are a relatively unexplored family of Ca(2+)-binding proteins.
      They are likely to be involved in many diverse areas of neuronal signalling. In
      this paper, we describe their expression in the rat brain as determined by in
      situ hybridization. As all five neuronal calcium sensor protein genes have
      distinctive expression patterns, they probably perform specific functions.

PMID- 10938427
TI  - Kindling causes persistent in vivo changes in firing rates and glutamate
      sensitivity of central piriform cortex neurons in rats.
AB  - The present experiments were undertaken to study whether amygdala kindling
      induces persistent alterations in the functional status of neurons of the central
      piriform cortex, a subregion of the piriform cortex identified previously as a
      site involved in the kindling process. Extracellular, single-unit recordings of
      piriform cortex neurons were made in anesthetized fully kindled rats at an
      interval of at least five weeks after the last seizure. Electrode implanted but
      not kindled rats served as sham controls. An additional group of non-implanted
      rats was used as naive controls. Spontaneously firing piriform cortex neurons
      were characterized in all groups by smooth, sharp, biphasic (i.e.
      positive/negative) action potentials with a duration of 0.8-1.8 ms, and were
      primarily located at the border between piriform cortex layers II and III. In
      kindled rats, neurons in the central piriform cortex exhibited a significantly
      higher firing rate compared to controls. Based on median group values, the
      increase in basal activity in kindled rats averaged about 90%. The responsiveness
      of piriform cortex neurons to neurotransmitters was tested by microiontophoretic
      application of glutamate, N-methyl-D-aspartate and GABA. Piriform cortex neurons
      of kindled rats exhibited a significantly lower responsiveness to the excitatory
      effect of glutamate than naive controls. A lowered glutamate responsiveness was
      also seen in sham controls. No significantly altered transmitter sensitivities of
      piriform cortex neurons from kindled rats were seen with N-methyl-D-aspartate or
      GABA. The data indicate that amygdala kindling causes persistent interictal
      changes in both basal activity and glutamate responsiveness of central piriform
      cortex neurons which could contribute to the abnormal hyperexcitability
      characteristic of kindling.

PMID- 10938428
TI  - Transient spine density increases in the mid-molecular layer of hippocampal
      dentate gyrus accompany consolidation of a spatial learning task in the rodent.
AB  - In previous studies, we observed a transient increase in dendritic spine
      frequency in the molecular layer of the dentate gyrus at 6h following passive
      avoidance training [O'Malley A., O'Connell C. and Regan C. M. (1998) Neuroscience
      87, 607-613]. To determine if a similar change is associated with spatial forms
      of learning, we have estimated time-dependent modulations of spine number in the
      dentate gyrus of the adult rat following water maze training. All animals
      exhibited significant reductions in the latency to locate the platform over the
      five training sessions of the single trial (median and interquartile ranges of
      60, 8 versus 8, 3 s for trials 1 and 5, respectively) and this improved
      performance was retained just prior to killing at the 6h post-training time. The
      unbiased dissector stereological procedure was used to estimate spine number in
      serial pairs of ultrathin coronal sections obtained at a point 3.3 mm caudal of
      Bregma. This analysis revealed a significant learning-associated increase in
      spine number at the 6h post-training time (1.32+/-0.18 spines/microm(3)) as it
      was not observed in paired controls exposed to the water maze for a similar swim
      time (0.66+/-0.11 spines/microm(3)). The increase was transient as spine number
      returned to control levels at the 72 h post-training time. These spine frequency
      changes are proposed to reflect increased synapse turnover rate and concomitant
      change in connectivity pattern in the processing of information for long-term
      storage.

PMID- 10938429
TI  - N-methyl-D-aspartate receptor subunit changes are associated with lead-induced
      deficits of long-term potentiation and spatial learning.
AB  - The present study demonstrates that impairments of spatial learning and
      hippocampal long-term potentiation in rats chronically exposed to lead are
      associated with changes in gene and protein expression of N-methyl-D-aspartate
      receptor subunits. Rats exposed to 750 and 1500 ppm lead acetate were found to
      exhibit deficits in acquisition of a water maze spatial learning task.
      Furthermore, lead-exposed rats show dose-dependent reductions in the maintenance
      of in vivo hippocampal long-term potentiation induced in entorhinal cortex
      dentate gyrus synapses. We found an unexpected, but significant (P<0.05),
      correlation between spatial learning and long-term potentiation when control and
      lead-exposed rats were analysed as a single, combined population. Dentate gyrus
      NR1 subunit messenger RNA was reduced 18% and 28% by exposure to 750 and 1500 ppm
      lead acetate, respectively. NR2A subunit messenger RNA was reduced 18% but only
      in the dentate gyrus of rats exposed to 1500 ppm lead acetate. No significant
      changes in dentate NR2B messenger RNA expression were measured in either of the
      lead-exposed groups. NR1 subunit protein was reduced 24% and 58% in hippocampal
      homogenates from rats exposed to 750 and 1500 ppm lead acetate. In contrast, no
      changes in NR2A or NR2B subunit protein were observed in the same hippocampal
      homogenates. These data show that reductions of specific N-methyl-D-aspartate
      receptor subunits are associated with deficits of both hippocampal long-term
      potentiation and spatial learning, induced in rats by chronic exposure to
      environmentally relevant levels of lead. These findings strongly suggest that the
      effects of lead on N-methyl-D-aspartate receptors may be the mechanistic basis
      for lead-induced deficits in cognitive function.

PMID- 10938430
TI  - Pattern of long-distance projections from fetal hippocampal field CA3 and CA1
      cell grafts in lesioned CA3 of adult hippocampus follows intrinsic character of
      respective donor cells.
AB  - Fetal hippocampal grafts transplanted to the lesioned CA3 of adult hippocampus
      can extend axonal projections to many regions of the host brain. However, the
      identity of grafted cells that project to specific host regions is unknown. We
      hypothesize that the pattern of long-distance axonal projections from distinct
      fetal hippocampal cells grafted to lesioned CA3 is specified by the intrinsic
      nature of respective donor cells rather than characteristics of the host graft
      region. We grafted fetal hippocampal CA3 or CA1 cells into kainic acid lesioned
      CA3 of adult hippocampus at four days post-lesion. Neurons projecting to either
      the contralateral hippocampus or the ipsilateral septum were then measured in
      these grafts at four months post-grafting using Fluoro-Gold and DiI tract
      tracing. CA3 grafts located close to the degenerated CA3 cell layer showed a high
      propensity for establishing projections into the contralateral hippocampus
      (commissural projections) compared to similarly located CA1 grafts, which
      exhibited negligible commissural projections. Similar distinction was observed
      between the two graft types even when they were located only partially in the
      lesioned CA3. Among CA3 grafts, those placed near the degenerated CA3 cell layer
      established significantly greater commissural projections than those placed only
      partially in the CA3 region. Septal projections, in contrast, were robust from
      both CA3 and CA1 grafts. This differential projection pattern between CA3 and CA1
      grafts resembles projections of CA3 and CA1 cells in intact hippocampus.These
      results demonstrate that the intrinsic character of grafted fetal cells
      determines the type of efferent projections from fetal grafts into different
      targets in the lesioned adult host brain. However, the extent of efferent
      projections from specific grafts is also influenced by the location of grafted
      cells within the host region. Thus, graft-mediated appropriate reconstruction of
      damaged circuitry in the lesioned brain may require grafting of homotopic donor
      cells. Further, the robust and specific projections observed from CA3 grafts is
      likely beneficial for functional recovery of hippocampus following CA3 injury and
      hence of significance towards developing a graft-mediated therapy for human
      temporal lobe epilepsy.

PMID- 10938431
TI  - Agonist stimulation provokes dendritic and axonal dopamine D(1) receptor
      redistribution in primary cultures of striatal neurons.
AB  - To investigate the influence of neurotransmitter on G-protein-coupled receptor
      trafficking and compartimentalization in neurons, we have developed a model of
      primary neuronal cultures from fetal rat striatum on which we have studied the
      cellular and subcellular distribution and trafficking of the D(1) dopaminergic
      receptor. This receptor is known to be somatodendritic and axonal targeted in
      vivo, mostly to extrasynaptic locations. Immunohistochemical studies at the light
      and electron microscopic levels showed that, in cultures, the D(1) dopaminergic
      receptor is expressed in the absence of dopamine stimulation. The pattern of D(1)
      dopaminergic receptor immunostaining after stimulation by the D(1) dopaminergic
      receptor agonist SKF 82958 (1 microM) is dramatically modified with a decrease of
      the number of labeled D(1) dopaminergic receptor puncta (-40%) and an increase of
      their size in both dendrites (+120%) and axons (+240%). Seven hours after removal
      of the agonist, return to normal pattern was observed. The D(1) dopaminergic
      receptor antagonist SCH 23390 (2 microM) abolishes the effect of SKF 82958.
      Electron microscopy demonstrated, in dendrites, a translocation of the labeling
      from the plasma membrane to endosomes. Axonal D(1) dopaminergic receptor
      redistribution after acute stimulation indicates that the D(1) dopaminergic
      receptor is membrane targeted and responsive to stimulation. These results
      validate primary culture of striatal neurons to study subcellular localization
      and intraneuronal trafficking of G-protein-coupled receptors. This preparation
      will be useful to address various questions concerning the behavior and the
      trafficking of these receptors in neurons in relation to the neurotransmitter
      environment.

PMID- 10938432
TI  - Enhanced intake of high-fat food following striatal mu-opioid stimulation:
      microinjection mapping and fos expression.
AB  - Our previous studies have shown that stimulation of mu-opioid receptors within
      the nucleus accumbens preferentially enhances intake of palatable food containing
      sucrose and fat; thus, opioids in this brain area may mediate the rewarding
      characteristics of food by modulating taste and macronutrient preference. The
      present study was designed to further explore the nature of the involvement of
      striatal opioids in feeding behavior, such as the location of sensitive
      subregions of the ventral striatum and the brain neural circuits involved in
      opioid-mediated hyperphagia. In Experiment 1, we conducted a microinfusion
      mapping study of feeding behavior by microinfusion of the mu receptor agonist, D
      Ala(2),NMe-Phe(4), Glyol(5)-enkephalin (0, 0.025 and 0.25 microg/0.5 microl per
      side; equivalent to 0, 0.04 and 0.40 nmol/0.5 microl per side), into several
      striatal subregions. In Experiment 2, detection of the expression of the
      immediate early gene, c-fos, was used to examine brain areas activated following
      intra-striatal microinfusion of D-Ala(2), NMe-Phe(4),Glyol(5)-enkephalin. The
      microinjection mapping study demonstrated a broad anatomical gradient within the
      striatum, with sensitivity highest in relatively more lateral and ventral regions
      of the striatum (ventrolateral striatum, lateral shell and core). The Fos mapping
      study demonstrated that circuitry including hypothalamic areas, the ventral
      tegmental area, the substantia nigra and the nucleus of the solitary tract was
      recruited by stimulation of mu receptors within the nucleus accumbens. A similar
      pattern was observed following stimulation of mu receptors in the dorsal
      striatum; however, the extent of activation was much smaller in magnitude. These
      results suggest that the role of mu receptors within the striatum in palatable
      feeding primarily involves ventral and lateral regions. Moreover, the pattern of
      activation in hypothalamic, midbrain and gustatory-visceral relay areas suggests
      that striatal mu receptors may participate in integrating motivational, metabolic
      and autonomic aspects of ingestive behavior.

PMID- 10938433
TI  - Haloperidol catalepsy consolidation in the rat as a model of neuromodulatory
      integration.
AB  - Haloperidol, a non-selective D(2) dopamine antagonist, both in vitro (1 microM)
      and in vivo (2.5 mg/kg i.p.), induced a long-term potentiation of K(+)-induced
      Ca(2+)-dependent release of endogenous noradrenaline and dopamine in rat brain
      cortical slices, by increasing the content of noradrenaline and dopamine known to
      be controlled by dopamine auto- and heteroreceptors. Haloperidol administration
      (2.5 mg/kg i.p.) evoked catalepsy and increased the content of noradrenaline and
      dopamine in the same structures of the brain. Haloperidol catalepsy consolidated
      without any additional learning and could be retrieved up to two weeks later by
      placing the animals in the test box. The catalepsy is disordered and retrieved
      only in the test box. The catalepsy was more intense on day 14 than on day 7.
      Injection of haloperidol immediately after conditioning evened the reflex
      retrieval on the following days. Moreover, learning increased the intensity of
      catalepsy in animals tested on the day of injection. Repeated testing of the
      reflex on the following days led to specific modifications of catalepsy
      retrieval. Pre-conditioned rats exhibited maximal catalepsy when tested
      immediately after being placed in the test box. These results suggest that both
      the processes of long-term potentiation and catalepsy consolidation are mediated
      by the same type of receptors, long-term modulation-inducing receptors.
      Endogenous neuromodulators, acting non-specifically or diffusely via their
      respective long-term modulation-inducing receptors, can initiate and consolidate
      generalized states which form the basis for emotional and motivational states.

PMID- 10938434
TI  - Effect of high-frequency stimulation of the subthalamic nucleus on the neuronal
      activities of the substantia nigra pars reticulata and ventrolateral nucleus of
      the thalamus in the rat.
AB  - Electrophysiological recordings were made in anaesthetized rats to investigate
      the mode of function of high-frequency stimulation of the subthalamic nucleus
      used as a therapeutic approach for Parkinson's disease. High-frequency electrical
      stimulation of the subthalamic nucleus (130 Hz) induced a net decrease in
      activity of all cells recorded around the site of stimulation in the subthalamic
      nucleus. It also caused an inhibition of the majority of neurons recorded in the
      substantia nigra pars reticulata in normal rats (94%) and in rats with 6
      hydroxydopamine lesions of the substantia nigra pars compacta (90%) or with
      ibotenic acid lesions of the globus pallidus (79.5%). The majority of cells
      recorded in the ventrolateral nucleus of the thalamus responded with an increase
      in their activity (84%). These results show that high-frequency stimulation of
      the subthalamic nucleus induces a reduction of the excitatory glutamatergic
      output from the subthalamic nucleus which results in deactivation of substantia
      nigra pars reticulata neurons. The reduction in tonic inhibitory drive of nigral
      neurons induces a disinhibition of activity in the ventrolateral motor thalamic
      nucleus, which should result in activation of the motor cortical system.

PMID- 10938435
TI  - Neurotrophin-4/5 promotes dendritic outgrowth and calcium currents in cultured
      mesencephalic dopamine neurons.
AB  - Ca(2+) currents and their modulation by neurotrophin-4/5 were studied in cultured
      mesencephalic neurons. Tyrosine hydroxylase-positive neurons consistently had
      larger somas than tyrosine hydroxylase-negative neurons. Neurons with larger
      somas were therefore targeted for recording. In both control and neurotrophin-4/5
      treated cultured neurons, isolation of Ca(2+) currents in cultured mesencephalic
      neurons revealed prominent low- and high-voltage-activated currents. These
      currents were separable based upon their voltage dependence of activation, the
      response to replacement of Ca(2+) with Ba(2+) and the response to Ca(2+) channel
      blockers. Replacement of Ca(2+) with Ba(2+) resulted in a slight reduction of low
      voltage-activated currents and a significant enhancement of high-voltage
      activated currents. Cd(2+) blocked a larger fraction of the high-voltage
      activated current than Ni(2+). The synthetic conotoxins SNX-124 and SNX-230
      selectively blocked high-voltage-activated currents. Morphological analysis of
      mesencephalic cultures pretreated with neurotrophin-4/5 revealed an increase in
      soma size and dendritic length in tyrosine hydroxylase-positive neurons. In
      agreement with the neurotrophin-4/5 induction of growth, neurotrophin-4/5 also
      increased cell capacitance in whole-cell recordings. Neurotrophin-4/5
      significantly enhanced both low- and high-voltage-activated currents, but
      normalization for changes in capacitance revealed only a significant increase in
      high-voltage-activated current density. This study demonstrates the existence of
      low-voltage-activated and multiple classes of high-voltage-activated calcium
      currents in cultured mesencephalic neurons. Morphological and physiological data
      demonstrate that the increases in calcium currents due to neurotrophin-4/5
      pretreatment are associated with somatodendritic growth, but an increase in high
      voltage-activated Ca(2+) channel expression also occurred.

PMID- 10938436
TI  - Insulin-like growth factor-1 and insulin mediate transient site-selective
      increases in tau phosphorylation in primary cortical neurons.
AB  - The modulation of tau phosphorylation and localization in response to insulin
      like growth factor-1 or insulin was examined in primary cultures of rat cortical
      neurons. Insulin and insulin-like growth factor-1 treatment resulted in a rapid
      and transient increase in tau phosphorylation at specific epitopes. These effects
      were completely inhibited by lithium, revealing that the insulin and insulin-like
      growth factor-1 induced changes in tau phosphorylation were mediated by glycogen
      synthase kinase-3beta. In addition, the increase in tau phosphorylation directly
      correlated with a transient dissociation of tau from the cytoskeleton, indicating
      that insulin and insulin-like growth factor-1 treatment resulted in a change in
      tau localization. Using immunocytochemistry, it was also demonstrated that
      treatment of neurons with insulin-like growth factor-1 for 3 min resulted in a
      redistribution of tau to the growth cone and the distal segment of the axons.
      Further, insulin-like growth factor-1 treatment resulted in an increased
      immunoreactivity with the phospho-dependent antibody AT8 in the same areas of the
      axons. Thus, the phosphorylation state and distribution of tau can be modulated
      by insulin and insulin-like growth factor-1 signaling pathways involving glycogen
      synthase kinase-3beta. We propose that by transiently increasing tau
      phosphorylation, insulin and insulin-like growth factor-1 may contribute to the
      reorganization of the cytoskeleton necessary for the development and growth of
      the neurites.

PMID- 10938437
TI  - Expression of amyloid precursor protein in human astrocytes in vitro: isoform
      specific increases following heat shock.
AB  - The beta-amyloid protein deposited in senile plaques and cerebral blood vessels
      in the Alzheimer's disease brain is derived from the larger transmembrane
      spanning amyloid precursor protein. The present study investigates the effects of
      heat shock on the expression and processing of amyloid precursor protein in a
      normal human fetal astrocytic cell line CC2565 using reverse transcription
      polymerase chain reaction, in situ hybridization histochemistry and western blot
      analysis. Heat shock led to an increase in the messenger RNA encoding Kunitz
      protease inhibitor isoforms of amyloid precursor protein, which peaked at 4h post
      heat shock. This increase was confined to the messenger RNA encoding amyloid
      precursor protein-751, with a decrease in amyloid precursor protein-770 and no
      change in amyloid precursor protein-695. This shift in splicing was accompanied
      by a significant decrease in secreted amyloid precursor protein and an increase
      in beta-secretase processing within the cell. These findings demonstrate that
      astrocytes in vitro demonstrate a striking response to heat shock. This is
      unlikely to be due to a direct action on the promoter region of the gene, since
      the response is specific for one splice variant; amyloid precursor protein-751
      messenger RNA. This increase in expression is further accompanied by a decrease
      in secretion of amyloid precursor protein, implying a shift in processing towards
      an intracellular route, possibly via the actions of the beta-secretase enzyme,
      which is known to be potentially amyloidogenic. Such a mechanism may contribute
      to amyloidosis in the intact brain in response to cellular stress, such as head
      injury.

PMID- 10938438
TI  - Role of the phosphatidylinositol-specific phospholipase C pathway in delta-opioid
      receptor-mediated antinociception in the mouse spinal cord.
AB  - Stimulation of delta-opioid receptors has been shown to activate phospholipase C
      via the activation of G-proteins in vitro. The present study was designed to
      determine, with the tail-flick method, whether the stimulatory effect of delta
      opioid receptor agonists on phospholipase C and inositol lipid turnover
      participates in the mechanisms of the delta-opioid receptor-mediated
      antinociception in the mouse spinal cord. Intrathecal pretreatment with the
      phospholipase C inhibitors neomycin and U73122, which produced no changes in the
      basal tail-flick latencies when they were injected alone, significantly
      attenuated the antinociception induced by intrathecal administration of the
      selective delta-opioid receptor agonist [D-Ala(2)]deltorphin II in mice. The
      selective phosphatidylinositol-specific phospholipase C inhibitor ET-18-OCH(3)
      inhibited the antinociception induced by intrathecal administration of [D
      Ala(2)]deltorphin II in a dose-dependent manner. In mice undergoing treatment
      with LiCl, which impairs phosphatidylinositol synthesis, the antinociception
      induced by intrathecal administration of [D-Ala(2)]deltorphin II was
      significantly reduced. Co-administration of D-myo-inositol-1,4,5-trisphosphate
      restored the [D-Ala(2)]deltorphin II-induced antinociception in LiCl-pretreated
      mice. On the other hand, intrathecal pretreatment with the selective protein
      kinase C inhibitor calphostin C, but not the protein kinase A inhibitor KT5720,
      resulted in a dose-dependent enhancement of the [D-Ala(2)]deltorphin II-induced
      antinociception. These results indicate a potential role for the phospholipase C
      inositol-1,4, 5-trisphosphate pathway in the expression of delta-opioid receptor
      mediated antinociception in the mouse spinal cord. Furthermore, activation of
      protein kinase C by the stimulation of delta-opioid receptors may constitute a
      significant pathway involved in negative modulation of spinal delta-opioid
      receptor-mediated antinociception.

PMID- 10938439
TI  - Functional role and therapeutic implications of neuronal caspase-1 and -3 in a
      mouse model of traumatic spinal cord injury.
AB  - Evidence indicates that both necrotic and apoptotic cell death contribute to
      tissue injury and neurological dysfunction following spinal cord injury. Caspases
      have been implicated as important mediators of apoptosis following acute central
      nervous system insults. We investigated whether caspase-1 and caspase-3 are
      involved in spinal cord injury-mediated cell death, and whether caspase
      inhibition may reduce tissue damage and improve outcome following spinal cord
      injury. We demonstrate a 17-fold increase in caspase-1 activity in traumatized
      spinal cord samples when compared with samples from sham-operated mice. Caspase-1
      and caspase-3 activation were also detected by western blot following spinal cord
      injury, which was significantly inhibited by the broad caspase inhibitor N
      benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. By immunofluorescence or in
      situ fluorogenic substrate assay, caspase-1 and caspase-3 expression were
      detected in neuronal and non-neuronal cells following spinal cord injury. N
      Benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone treated mice, and transgenic
      mice expressing a caspase-1 dominant negative mutant, demonstrated a significant
      improvement of motor function and a reduction of lesion size compared with
      vehicle-treated mice. Our results demonstrate for the first time that both
      caspase-1 and caspase-3 are activated in neurons following spinal cord injury,
      and that caspase inhibition reduces post-traumatic lesion size and improves motor
      performance. Caspase inhibitors may be one of the agents to be used for the
      treatment of spinal cord injury.

PMID- 10938440
TI  - Growth factor regulation of neurogenesis in adult olfactory epithelium.
AB  - Neurogenesis continues throughout adult life in the mammalian olfactory
      epithelium. This process is a dynamic state of proliferation, differentiation and
      cell death, probably regulated by autocrine and paracrine signals such as peptide
      growth factors. Previous investigations have demonstrated roles for some growth
      factors in olfactory neurogenesis in vitro, but the assay systems used make it
      difficult to be certain of their effects (proliferation, differentiation,
      enhanced survival) or their target cells. The present study investigated the
      effects of growth factors in cultures of purified olfactory epithelium comprising
      only basal cells and supporting cells in serum-free media. The advantage of this
      culture system is that proliferation, differentiation and survival of the basal
      cells and neurons can be examined separately. Under these conditions, three
      growth factors exerted well-defined effects: (i) fibroblast growth factor-2
      stimulated proliferation of the globose basal cells; (ii) transforming growth
      factor-beta2 induced these cells to differentiate into neurons; and (iii)
      platelet-derived growth factor promoted survival of the differentiated neurons.
      We conclude that fibroblast growth factor-2, transforming growth factor-beta2 and
      platelet-derived growth factor act sequentially on precursor cells and immature
      neurons during neurogenesis in the adult olfactory epithelium.

PMID- 10938441
TI  - Visceral inputs to neurons in the anterior hypothalamus including those that
      project to the periaqueductal gray: a functional anatomical and
      electrophysiological study.
AB  - The present study was designed to examine peripheral, in particular noxious
      visceral, inputs to neurons in the hypothalamus that project to the midbrain
      periaqueductal gray. The induction of Fos protein was used to localize
      hypothalamic neurons that were activated by noxious visceral stimulation. This
      was combined with retrograde transport of fluorescent latex microspheres from
      identified "pressor" and "depressor" sites in the dorsolateral/lateral or
      ventrolateral columns of the periaqueductal gray. A second series of
      electrophysiological experiments examined the receptive field characteristics,
      including the incidence of viscerosomatic convergence, of neurons in the ventral
      part of the anterior hypothalamus. Noxious visceral stimulation (intraperitoneal
      acetic acid) induced Fos-like immunoreactivity in significantly more neurons in
      the hypothalamus than control stimuli (intraperitoneal saline and intravenous
      phenylephrine). Particularly high numbers of Fos-positive neurons were found in
      the paraventricular nucleus, the supraoptic nucleus and ventral regions of the
      anterior hypothalamus. When combined with retrograde tracing from "depressor"
      sites in the ventrolateral periaqueductal gray, the highest numbers of double
      labelled neurons were localized in the paraventricular nucleus and the lateral
      area of the anterior hypothalamus. However, the regions that contained the
      greatest proportions of Fos-positive neurons that projected to "depressor" sites
      in the ventrolateral periaqueductal gray were the lateral area of the anterior
      hypothalamus and its rostral extension, the lateral preoptic area. Fewer double
      labelled neurons were localized in the hypothalamus after retrograde transport
      from sites in the dorsolateral/lateral periaqueductal gray compared to the
      results obtained from injections of tracer in the ventrolateral periaqueductal
      gray. Furthermore, the numbers of Fos-positive hypothalamic neurons that
      projected to the dorsolateral/lateral periaqueductal gray were very similar in
      experimental and control animals. The electrophysiological study confirmed that a
      large proportion of neurons in and around the lateral area of the anterior
      hypothalamus can be driven by noxious visceral stimulation and demonstrated a
      high incidence of viscerosomatic convergence in these cells (66% of cells driven
      from somatic structures were also driven by electrical stimulation of the
      splanchnic nerve). Somatic receptive fields of these neurons were generally
      large, often including all four limbs and the face. The results of the functional
      anatomical and electrophysiological studies have identified neurons in an area of
      the ventral anterior hypothalamus that are a focus of nociceptive visceral input
      and which project to the midbrain periaqueductal gray, in particular to its
      ventrolateral column. These results are discussed in relation to the roles of the
      anterior hypothalamus and the different longitudinal columns of the
      periaqueductal gray in co-ordinating autonomic and sensory functions in response
      to visceral pain.

PMID- 10938442
TI  - Integration of thermal and osmotic afferent signals in the preoptic/anterior
      hypothalamic neurons.
AB  - Our in vivo experiments were aimed at studying afferent links of the
      preoptic/anterior hypothalamus system, which integrates thermal and osmotic
      homeostasis. Special attention was paid to using stimulation intensities within
      the normal physiological range. The experiments were carried out on adult cats
      anesthetized with ketamine (25mg/kg) and inhalation of nitrous oxide (75 vol.%).
      Short-term shifts in the osmotic pressure within the cerebral vasculature were
      induced by infusions of 200-500 microl 3.0% or 0.2% NaCl solutions into the
      homolateral a. carotis (hyper- and hypoosmotic stimulations, respectively).
      Thermal stimulation was provided by local heating or cooling of the contralateral
      forelimb pad skin (+/-7.0 degrees C range). Reactions of preoptic/anterior
      hypothalamus neurons were classified into four types: monophasic activation,
      monophasic inhibition, and biphasic responses including excitation followed by
      inhibition or primary inhibition followed by activation. Monophasic activation
      was a very common occurrence among preoptic/anterior hypothalamus neuronal
      reactions. The responsiveness of thermosensitive preoptic/anterior hypothalamus
      neurons to hyperosmotic stimulation turned to be noticeably higher than that to
      hypoosmotic stimulation. Practically equal proportions of warm- and cold
      sensitive neurons demonstrated changes in the firing activity resulting from
      intracarotid infusions of 3.0% NaCl solution. Infusions of 0.2% NaCl solution
      induced firing rate modifications in 26% (12/46) of warm-sensitive and in 32%
      (18/39) of cold-sensitive neurons. Cold-sensitive neurons displayed a higher
      sensitivity to a short-term osmotic pressure elevation in the cerebral
      vasculature (63%, 33/52) than warm-sensitive neurons did (43%, 22/52, P<0.05). In
      our study, a maximum similarity in the response types was observed when
      hyperosmotic infusion and skin cooling were applied, while a maximum disagreement
      was found when hyperosmotic stimulations were combined with skin heating. There
      is no doubt that preoptic/anterior hypothalamus neurons play a crucial role in
      the maintenance of body temperature. Several studies have also shown that
      osmoregulation can be affected by shifts in peripheral and hypthalmic
      temperatures. Information on the neurol mechanisms of interactions between the
      thermo- and osmoregulatory circuits in the hypothalamus remains limited. We
      discuss the obtained data considering the "set-point theory" of thermal
      hameostasis maintenance.

PMID- 10938443
TI  - Regulation of brain-derived neurotrophic factor messenger RNA levels in avian
      hypothalamic slice cultures.
AB  - Mechanisms regulating the expression of brain-derived neurotrophic factor, a
      member of the neurotrophin family, have been extensively studied in the rat
      cerebral cortex, hippocampus and cerebellum. In contrast, little is known
      regarding the regulation of this growth factor in the hypothalamus. Here we
      present an analysis of the regulation of brain-derived neurotrophic factor
      messenger RNA levels in chick embryo hypothalamic slice cultures following
      exposure to potassium chloride, glutamate agonists and sex steroids. Following a
      week in chemically-defined media the tissue was depolarized by exposure to 50 mM
      potassium chloride for 6h, resulting in a significant 4.2-fold increase in the
      level of brain-derived neurotrophic factor messenger RNA. This result is
      consistent with studies of other brain regions. Similar 6-h acute exposures of
      the hypothalamic cultures to 25 microM N-methyl-D-aspartic acid, 25 microM kainic
      acid and 25 microM alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid also
      significantly increased messenger RNA levels 2.5-, 2.1- and 1.4-fold,
      respectively. It was previously reported that brain-derived neurotrophic factor
      levels within the rat cerebral cortex, olfactory bulb and hippocampus are altered
      by exposure to 17beta-estradiol. Here we show that in hypothalamic slice cultures
      neither acute nor chronic treatments with 10 and 100 nM 17beta-estradiol and 10nM
      testosterone significantly altered the steady-state level of this growth factor.
      These findings show that neuronal activity, induced by glutamate agonists and
      potassium chloride, can regulate brain-derived neurotrophic factor messenger RNA
      levels within embryonic hypothalamic slice cultures. This regulation could play a
      critical role in the modulation of programmed cell death and synaptic maturation
      during development of the hypothalamus.

PMID- 10938444
TI  - Quantitative changes in reduced nicotinamide adenine dinucleotide phosphate
      diaphorase-reactive neurons in the brain of Octodon degus after periodic maternal
      separation and early social isolation.
AB  - The influence of preweaning maternal separation and postweaning social isolation
      on the development of reduced nicotinamide adenine dinucleotide phosphate (NADPH)
      diaphorase-reactive neurons in prefrontal cortical areas, in subdivisions of the
      nucleus accumbens and in the corpus callosum was quantitatively investigated in
      the precocious rodent Octodon degus. Forty-five-day-old degus from three animal
      groups were compared: (i) degus that were reared under normal undisturbed social
      conditions; (ii) degus that were repeatedly separated from their mothers during
      the first three postnatal weeks and thereafter reared with their family; and
      (iii) degus that remained undisturbed with the family until weaning (postnatal
      day 21) and thereafter were reared in social isolation. Preweaning maternal
      separation led to a significant decrease in NADPH-diaphorase-containing neurons
      in the corpus callosum in both genders (down to 33%) compared with the social
      control group. No significant changes were found in the subregions of the medial
      prefrontal cortex and nucleus accumbens. Postweaning social isolation led to a
      reduced density of NADPH-diaphorase-containing neurons in the corpus callosum in
      both genders (down to 52%) compared with the social control group. Furthermore,
      in the precentral medial cortex of female pups, a significant reduction in NADPH
      diaphorase-reactive neurons (down to 72%) was detectable. All other regions of
      the medial prefrontal cortex and the nucleus accumbens remained unchanged. The
      observed deprivation-induced changes may reflect either an excessive reduction in
      NADPH-diaphorase-positive neurons or a down-regulation of the enzyme in neurons
      that normally express it.Our results indicate a link between early adverse socio
      emotional experience and the maturation of NADPH-reactive neurons. Further
      studies are required to analyse the functional implications of this experience
      induced brain pathology.

PMID- 10938445
TI  - A-type potassium current in myenteric neurons from guinea-pig small intestine.
AB  - Biophysical properties of A-type K(+) currents (I(A)) in myenteric neurons from
      guinea-pig small intestine were studied. I(A) was present in both AH- and S-type
      myenteric neurons. Reduction of external Ca(2+) did not affect the current.
      Current density was 13.5+/-10.2 pA/pF in 68 AH-type neurons and 23.4+/-8.2 pA/pF
      in 31 S-type neurons. S-type neurons appeared to be a homogeneous group based on
      density of I(A). AH-type neurons were subdivided into two groups with current
      densities of 9.4+/-4.3 and 25.4+/-4.3 pA/pF. All other biophysical properties of
      the current were not statistically different for AH- and S-type neurons. Steady
      state activation and inactivation curves showed half-activation potentials at -7
      mV (k=15. 0 mV) and -86 mV (k=11.5 mV). The curves overlapped at potentials near
      the resting potential of approximately -55 mV. Time constants for activation
      ranged from 3.6 to 0.52 ms at test potentials between -20 and 50 mV. Inactivation
      time constants fell between 41.5 and 11 ms at test potentials between -20 and 50
      mV. Time constants for recovery from inactivation fit a double-exponential curve
      with fast and slow recovery times of 11 and 550 ms. 4-Aminopyridine suppressed
      I(A) when it was activated at -20 mV following a pre-pulse to -110 mV. Addition
      of Zn(2+) in the external solution resulted in a concentration-dependent shift of
      the activation and inactivation curves in the depolarized direction. Zn(2+)
      slowed the activation and inactivation kinetics of I(A) by factors of 3.3- and
      1.2-fold over a wide range of potentials. Elevation of external H(+) suppressed
      the effect of Zn(2+) with a pK of 7.3-7.4. The effects of Zn(2+) were interpreted
      as not being due to surface charge screening, because the affinity of Zn(2+) for
      its binding site on the A-channel was estimated to be between 170 and 312 microM,
      while the background concentration of Mg(2+) was 10 mM. The enteric nervous
      system is perceived as an independent integrative nervous system (brain-in-the
      gut) that is responsible for local organizational control of motility and
      secretory patterns of gut behavior. AH- and S-type neurons are synaptically
      interconnected to form the microcircuits of the enteric nervous system. The
      results suggest that I(A) is a significant determinant of neuronal excitability
      for both the firing of nerve impulses and the various synaptic events in the two
      types of neurons.

PMID- 10938446
TI  - Reduced plasma leptin concentrations in bulimia nervosa.
AB  - Leptin is a protein produced by the ob-ob gene which inhibits food intake. Plasma
      levels have previously been reported to be altered in obesity and anorexia
      nervosa (AN) but not bulimia nervosa (BN). We measured fasting plasma leptin
      levels by radioimmunoassay in 53 subjects carefully studied at NIMH, including 37
      women meeting DSM-III-R criteria for BN [10 with concurrent AN (body mass index
      (BMI)=14.1+/-1.4), 27 without AN (BMI=20.4+/-1.6)] and 16 normal control women
      (NCs) (BMI=21.1+/-2.0). Patients were medication-free and abstinent from bingeing
      and purging for three to four weeks prior to study. Plasma leptin levels were
      significantly correlated to BMI (r=0.41, P<0.002), weight (kg, r=0.43, P<0.001),
      and percent average body weight (%ABW, r=0.45, P<0.001) in the total group.
      Plasma leptin levels were lower in the BN subjects (3.4+/-2.5 ng/ml) compared to
      the NCs (6.1+/-2.6 ng/ml, P<0.001, ANCOVA) even after controlling for BMI and
      weight. There was no significant difference between BN subjects with AN (n=10,
      2.6+/-2.6 ng/ml) and those without AN (n=27, 3.8+/-2.4 ng/ml), despite lower BMI
      in BN with AN. Furthermore, leptin levels were decreased in BN without AN
      compared with healthy controls, even though BMI was comparable in these two
      subgroups. Plasma leptin concentrations were negatively correlated with baseline
      plasma cortisol levels (n=49, r=-0.49, P<0.001) and positively correlated with
      prolactin responses following L-tryptophan (n=49, r=0.37, P<0.009) and m
      chlorophenylpiperazine (n=52, r=0.24, P<0.09). This is the first known report of
      decreased plasma leptin levels in BN. The decrement in leptin concentration is
      not related to BMI, body weight, or the presence or absence of BN. HPA axis
      activation as well as serotonin dysregulation may be related to decreased leptin
      levels, which may in turn contribute to disinhibited eating in BN. Although
      current leptin levels were not correlated with self-reported previous binge
      frequency, the role of leptin in the pathophysiology of BN deserves further
      study.

PMID- 10938447
TI  - Plasma 5alpha-androstane-3alpha,17betadiol, an endogenous steroid that positively
      modulates GABA(A) receptor function, and anxiety: a study in menopausal women.
AB  - We tested the hypothesis that changes in endogenous neuroactive steroids acting
      as positive allosteric modulators of gamma-aminobutyric acid (GABA)(A) receptors
      may be related to the menopause-associated mood alterations. The study sample
      consisted of twenty five drug-free menopausal women, 1-3 years since the onset of
      menopause, homogeneous for age and body mass index (BMI) and without personal
      history of psychiatric, metabolic or endocrine disorders. Depression and anxiety
      related symptoms were assessed with the Zung Self-administered Depression Scale
      (ZSDS) and the Cornell's Dysthymia Rating Scale (CDRS). The cut-off value
      predicted by the ZSDS index defined two groups of women (asymptomatic [35.5+/
      4.6, n=12] and symptomatic [60.8+/-7.9, n=13]), that were also significantly
      different according to the CDRS scores (10.6+/-3.4 and 31.5+/-12, respectively,
      P<0.05). Upon evaluation of the scores relative to the anxiety factor of the CDRS
      (items 11-15) the symptomatic, but not the asymptomatic, group showed a moderate
      level of anxiety. The plasma concentrations of several neuroactive steroids were
      measured, after extraction and HPLC purification, by radioimmunoassay with
      specific antisera. Only dehydroepiandrosterone and its metabolite 5alpha
      androstane-3alpha,17betadiol (3alpha-ADIOL), a positive allosteric modulator of
      GABA(A) receptors, were significantly (P<0.05 and P<0.005) higher (+110% and
      +64%, respectively) in the asymptomatic group. A highly significant and negative
      correlation (r=-0.672, P=0.003) was found between the plasma 3alpha-ADIOL
      concentrations and the scores of the anxiety factor of the CDRS. These data
      suggest that endogenous 3alpha-ADIOL modulates the central GABAergic tone and
      that higher 3alpha-ADIOL concentrations could have a role in preventing the
      expression of anxiety in the asymptomatic women.

PMID- 10938448
TI  - Smoking behavior, dysphoric states and the menstrual cycle: results from single
      smoking sessions and the natural environment.
AB  - A 2-way factorial repeated measures design examined the effects of menstrual
      cycle phase and smoking on: 1) smoking behavior, 2) mood state, 3) nicotine
      withdrawal symptomatology, and 4) menstrual symptomatology. Female smokers, aged
      20-39, were followed for two consecutive menstrual cycles with two data
      collection sessions per cycle, which were conducted in the University's General
      Clinical Research Center (GCRC). Participants were randomly assigned to order of
      smoking condition, which included: 1) smoking ad libitum, and 2) 24-hour
      abstinence prior to data collection. Data were collected in the mid-to-late
      follicular (MLF) phase (between days 6 through to 11) and the four days prior to
      menses in late luteal (LL) phase. Participants completed the Profile of Mood
      States and Menstrual Symptom Severity List and recorded daily cigarette smoking
      rate in the natural environment during MLF and LL phases. Nicotine boost and
      carbon monoxide (CO) boost were measured and the Shiffman-Jarvick Tobacco
      Withdrawal Questionnaire was administered during GCRC data collection sessions.
      Results indicated that subjects smoked more cigarettes per day during the LL
      phase and CO boost was greater during MLF. No difference was noted in nicotine
      boost by condition or phase. No difference in mood state was noted by either
      condition or phase. Withdrawal symptomatology and craving for cigarettes were
      increased after 24 hours of abstinence. No difference was noted in menstrual
      symptoms by condition or phase. Further investigations are still needed to
      characterize the importance of cycle phase in the design of smoking cessation
      interventions for women of reproductive age.

PMID- 10938449
TI  - The differential effect of the anxiolytic agent 8-OH-DPAT during lactation is
      independent of pup withdrawal and maternal behavior.
AB  - Injection of the serotonergic agonist, 8-hydroxy-2-(di-n-propylamino-tetralin (8
      OH-DPAT) (0.5 mg/kg ip) produced a clear anxiolytic-like effect (as measured in
      the burying behavior test), after parturition, which remains until day 6 of
      lactation. Thereafter 8-OH-DPAT completely lacked action. In order to analyze
      whether lactation prevented the action of 8-OH-DPAT, dams were separated from
      their pups for five consecutive days. The blockade of the anxiolytic effect of 8
      OH-DPAT does not disappear by isolation of the mothers from their offspring or
      from neighboring pups. Finally, to investigate the possible role of maternal
      behavior in the blockade of the anxiolytic effect of 8-OH-DPAT a third experiment
      was made in which ovariectomized females were rendered maternal by the
      sensitization procedure. These females respond normally to the antianxiety
      actions of 8-OH-DPAT. Results suggest that a long-term clue triggered by
      lactation, possibly related to prolactin secretion, interferes with the
      anxiolytic effect of 8-OH-DPAT.

PMID- 10938450
TI  - Genetic factors, perceived chronic stress, and the free cortisol response to
      awakening.
AB  - Recent studies have demonstrated that the free cortisol response to awakening can
      serve as a useful index of hypothalamus-pituitary-adrenal axis (HPA) activity.
      This endocrine marker is rather consistent, shows good intraindividual stability
      across time and appears to be able to uncover subtle changes in HPA regulation.
      The present twin study investigated genetic factors as sources of the
      interindividual variation of the cortisol awakening response. Furthermore, the
      relationship between psychological variables and morning cortisol levels was
      studied. On two consecutive days saliva samples were collected 0, 30, 45 and 60
      minutes after awakening in 52 monozygotic and 52 dizygotic twin pairs. Moreover,
      samples were obtained at 0800, 1100, 1500 and 2000 h. ('short day-time profile').
      Additionally, the participants filled out questionnaires assessing chronic stress
      load, self-esteem and self-efficacy.Heritability estimates of h(2)=0.40 for the
      mean increase and of h(2)=0.48 for the area under the response curve indicate a
      significant impact of genetic factors on cortisol levels after awakening.
      However, no genetic influence on the short day-time profile could be observed.
      Furthermore, several aspects of perceived chronic stress, namely 'worries',
      'social stress' and 'lack of social recognition' were significantly associated
      with the awakening cortisol response. The evidence for a medium-sized, yet
      distinct genetic influence on cortisol levels after awakening is discussed with
      regard to a potential clinical relevance of genetic determinants of HPA
      (re)activity. In line with several recent studies, the present findings further
      support the view that the cortisol awakening responses is consistently enhanced
      under chronic stress conditions.

PMID- 10938451
TI  - Biosocial aspects of domestic violence.
AB  - Domestic violence, defined as acts of verbal abuse and physical violence
      performed against women by current intimate main partners, was surveyed by means
      of the Conflict Tactics Scale. We examined the relationships between a biological
      variable (testosterone level), social variables (demographics, social
      integration), and behaviour (substance use) and self-reported domestic violence.
      Forced-entry OLS regression models allowed us to study how social and behavioural
      variables modified the effects of testosterone on this specific violent
      behaviour. The sample consisted of 54 men who had a main sexual partner and who
      identified themselves as Black, White, or Hispanic. The men were recruited from
      various social-service-agency sites in the area of Miami, Florida, on the basis
      of their risk factors for HIV/AIDS. The sample can best be described as
      culturally diverse men of low socioeconomic status who had a main sexual partner.
      A high percentage of participants reported some level of both verbal and physical
      aggression towards their partners. Testosterone levels were significantly
      associated with levels of both verbal aggression and physical violence self
      reported by the men. Testosterone level, demographic characteristics, and alcohol
      consumption contributed to explaining the variance in self-reported verbal and
      physical abuse. The high heritability of testosterone level and its association
      with violent behaviour warrant the inclusion of this variable in studies of
      antisocial and criminal behaviour including domestic violence.

PMID- 10938452
TI  - Multihormonal responses to clonidine in patients with affective and psychotic
      symptoms.
AB  - The neuroendocrine responses to the alpha(2)-adrenoreceptor agonist clonidine
      (CLO) (0.35 mg if body weight <65 kg or 0.375 mg if body weight> or =65 kg, PO)
      were studied in a large group of subjects: 134 drug-free inpatients--with either
      DSM-IV schizophrenia (SCZ, n=31), schizoaffective disorder (SAD, n=16), or major
      depressive episode (MDE, n=87) - and 22 hospitalized controls (HCs). Comparison
      with a previous placebo test performed in a subgroup of 92 subjects (46 MDEs, 20
      SCZs, 8 SADs, and 18 HCs) showed that CLO induced a significant increase of
      growth hormone, prolactin (PRL) and thyrotropin (TSH) levels but no significant
      change in adrenocorticotropin and cortisol release. According to diagnostic
      categories, we found significantly lower GH stimulation in MDEs and in SADs
      compared to HCs or to SCZs. In addition, we found significantly lower CLO induced
      PRL and TSH stimulations in paranoid SCZ patients compared to controls and
      disorganized SCZ patients. Taken together, these results suggest a
      hyposensitivity of noradrenergic alpha(2)-receptors in patients with affective
      symptoms.

PMID- 10938453
TI  - Induction of nuclear factor kappaB but not kappaB-responsive cytokine expression
      during myocardial reperfusion injury after neutropenia.
AB  - Neutrophils may contribute to myocardial ischemia/reperfusion (I/R) injury by
      generating reactive oxygen intermediates (ROIs). ROIs activate nuclear factor
      (NF)-kappaB, which regulates genes for cytokines with negative inotropic effects
      (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha). We
      investigated the impact of neutrophil depletion on NF-kappaB DNA binding
      activity, and expression of these cytokines during myocardial I/R injury. Male
      WKY rats (n = 28) received a single dose of antineutrophil antiserum (i/v).
      Twenty two hours later, when the peripheral blood neutrophil counts were
      profoundly decreased (94% reduction), the animals underwent 15 min of left
      anterior descending coronary artery ligation followed by reperfusion for 0.25,
      0.5, 1, 2, 3, and 6 h (n = 4/group). Saline-treated animals underwent a similar
      protocol, and served as controls (n = 28, 4/group). Neutrophil accumulation,
      defined by myeloperoxidase activity, was present in controls, but not in anti-PMN
      antisera-treated animals (at least p <0.05 at 1, 2, 3, and 6 h R). Despite this
      difference, in both saline- and antiserum-treated animals, the GSH levels were
      very similar and fell significantly (p < 0.0001) at 15 min R; the levels
      increased gradually over time. In contrast, GSSG levels rose at 15 and 30 min R
      (p < 0.05), and declined thereafter. NF-kappaB DNA binding activity increased in
      both groups at 15 min and again at 3 h of R. Both NF-kappaBp50 and p65 subunits
      were detected by supershift assay. In saline-injected controls both mRNA and
      protein for IL-1beta, IL-6, and TNF-alpha were detected at 1 h R; levels remained
      high until 3 h, then fell (except IL-6, which was elevated at 6 h). In
      neutropenic animals, however, a significant decrease in mRNA (at least 1.7-fold,
      p < 0.05) as well as protein levels (at least 2. 3-fold, p < 0.01) for all three
      cytokines was observed. Thus, while neutrophils had minimal effects on oxidative
      stress (GSH/GSSG) and oxidative stress-responsive NF-kappaB activity, they
      contributed significantly to myocardial cytokine expression.

PMID- 10938454
TI  - Two-photon microscopy of aorta fibers shows proteolysis induced by LDL
      hydroperoxides.
AB  - Oxidatively modified LDL mimics several aspects of atherogenesis. In this
      disease, degradation of the matrix proteins' network also occurs. By a new
      morphological ex vivo approach, not requiring sample processing, we explored the
      relationship between the degradation of matrix protein and oxidatively modified
      LDL. Two-photon excitation fluorescence microscopy images of fresh cross-section
      rings of rat aorta, acquired while the sample was maintained in a glucose- and
      oxygen-supplemented buffer, showed straight, parallel, thick, long extracellular
      matrix proteins. Traditional microscopic examination, requiring sample fixation
      and staining, shows smaller and curved fibers. Instead, we observed curved and
      broken fibers after a 30-min incubation of aorta with either LDL containing lipid
      hydroperoxides, or tert-butyl-hydroperoxide. The adhesion of LDL to the
      endothelium and its internalization was directly visualized by using a lipid
      fluorophore. The damage to aorta matrix proteins induced by LDL and tert-butyl
      hydroperoxide was fully prevented by antioxidants, such as ascorbate or Trolox C,
      or inhibitors of proteases. The image spectroscopy of the fibers'
      autofluorescence (polarization and lifetime) revealed an increased mobility of
      the fluorescent cross-link in fibers. Damaged matrix proteins were also imaged in
      aorta samples from apolipoprotein E knock-out mice. Our ex vivo images directly
      visualized the activation of a fast redox-sensitive proteolytic process in the
      arterial wall triggered by lipid hydroperoxides in LDL.

PMID- 10938455
TI  - Stress proteins as biomarkers of oxidative stress: effects of antioxidant
      supplements.
AB  - The potential benefits to health of the supply of antioxidants, either through
      dietary intake or as supplements, is equivocal. There is a need to develop
      biomarkers that may act as monitors of cellular defense as influenced by
      antioxidant status. Thirty-two individuals participated in the project and 19
      received supplements for 5 weeks in the form of a capsule containing a defined
      mixture of antioxidants. No change was noted in levels of superoxide dismutase
      and glutathione peroxidase following antioxidant supplementation. On the other
      hand, increase in total antioxidant status and decrease in malondialdehyde,
      protein carbonyl formation, and erythrocyte hemolysis were noted. In lymphocytes
      isolated from individuals receiving antioxidant supplements and subjected to a
      heat shock in the presence of the free radical generator 2, 2'-azobis-(2
      amidinopropane)-dihydrochloride, enhanced synthesis of heat shock proteins hsp
      105, hsp 90, hsp 70, and hsp 40 by contrast with decreased synthesis of heme
      oxygenase HO-1 (hsp 32) were noted. We conclude that antioxidant status modulates
      the synthesis of stress proteins.

PMID- 10938456
TI  - 13C NMR evidence of the failure of human erythrocytes to metabolize ascorbate and
      dehydroascorbate to lactate.
AB  - 13C-NMR spectroscopy was used to record time courses of the metabolism of [1
      (13)C]-L-ascorbic acid (AA) and [2-(13)C]-L-ascorbic acid and their dehydro
      counterparts (DHAA) by human erythrocytes. Under a range of experimental
      conditions, but most notably in the absence of glucose in the incubation medium,
      no (13)C-NMR signal for lactate emerged during any of the 5 h time courses. The
      NMR resonances that did emerge over time were assigned to diketogulonic (DKG)
      acid and CO(2). Only very minor resonances from degradation products of DKG
      appeared from samples that contained physiologically high concentrations of DHAA.
      These results are in contrast with those in a recent report that lactate is
      derived from AA in human erythrocytes. However, an explanation for this possible
      artifact is given.

PMID- 10938457
TI  - Oxidative cellular damage associated with transformation of Helicobacter pylori
      from a bacillary to a coccoid form.
AB  - Exposure to unfavorable conditions results in the transformation of Helicobacter
      pylori, a gastric pathogen, from a bacillary form to a coccoid form. The
      mechanism and pathophysiological significance of this transformation remain
      unclear. The generation of the superoxide radical by H. pylori has previously
      been shown to inhibit the bactericidal action of nitric oxide, the concentration
      of which is relatively high in gastric juice. With the use of chemiluminescence
      probes, both the quality and quantity of reactive oxygen species generated by H.
      pylori have now been shown to change markedly during the transformation from the
      bacillary form to the coccoid form. The transformation of H. pylori was
      associated with oxidative modification of cellular proteins, including urease, an
      enzyme required for the survival of this bacterium in acidic gastric juice.
      Although the cellular abundance of urease protein increased during the
      transformation, the specific activity of the enzyme decreased and it underwent
      aggregation. Specific activities of both superoxide dismutase and catalase in H.
      pylori also decreased markedly during the transformation. The transformation of
      H. pylori was also associated with oxidative modification of DNA, as revealed by
      the generation of 8-hydroxyguanine, and subsequent DNA fragment. These
      observations indicate that oxidative stress elicited by endogenously generated
      reactive oxygen species might play an important role in the transformation of H.
      pylori from the bacillary form to the coccoid form.

PMID- 10938458
TI  - Arachidonic acid induces calcium-dependent mitochondrial formation of species
      promoting strand scission of genomic DNA.
AB  - Both the phospholipase A(2) activator melittin and reagent arachidonic acid (AA)
      are poor inducers of DNA single strand breaks in U937 cells. These responses,
      however, were dramatically increased by the calcium-mobilizing agent caffeine
      (Cf) or by the respiratory substrate pyruvate via a mechanism that involved
      enforced mitochondrial Ca(2+) accumulation and that was sensitive to lipoxygenase
      inhibitors. In permeabilized cells, the DNA damage generated by AA in combination
      with either Cf, L-malate or CaCl(2) was blunted by catalase. AA generated DNA
      strand scission also in HeLa cells supplemented with pyruvate via a mechanism
      identical to that observed in U937 cells. This response was associated with an
      enforced formation of free radical species. These results demonstrate that
      mitochondria play a pivotal role in the DNA-damaging response evoked by AA and
      provide the bases for a calcium-dependent mechanism whereby the AA produced
      during inflammatory processes may affect various pathologic conditions, including
      carcinogenesis.

PMID- 10938459
TI  - Involvement of differential metallothionein expression in free radical
      sensitivity of RTG-2 and CHSE-214 cells.
AB  - The role of metallothionein (MT) in free radical regulation and scavenging was
      investigated using two fish cell lines, the rainbow trout gonadal (RTG-2) cell
      line and the chinook salmon embryonic (CHSE-214) cell line. Exposure of RTG-2
      cells to H(2)O(2) resulted in upregulation of both MT mRNA and MT protein and was
      also demonstrated by immunocytochemistry, confirming that MT was regulated by
      free radicals. We then compared the H(2)O(2) resistance in RTG-2 and CHSE-214
      cells following metal treatment with Zn or Cd to induce MT. Comparison of
      survival of control cells and metal-exposed cells showed that metal treatment,
      which induced MT, significantly raised the H(2)O(2) tolerance in a dose-dependent
      manner in RTG-2 cells, while no increased H(2)O(2) resistance was observed in
      CHSE-214 cells. Transient over-expression of MT in CHSE-214: 59 cells also
      resulted in a dose-dependent increase in resistance to H(2)O(2) exposure. The
      raised resistance against H(2)O(2) in metal treated RTG-2 cells as well as
      transfected CHSE-214: 59 cells strongly demonstrate that MT is involved in the
      protection against H(2)O(2) and suggest a physiologically important function for
      MT when cells or whole organisms are exposed to oxidative stress.

PMID- 10938460
TI  - Mechanism of action in a 4,5-diarylpyrrole series of selective cyclo-oxygenase-2
      inhibitors.
AB  - Using semi-empirical AM1 calculation and 6.31G* basis sets, we have calculated
      the energy of the highest-occupied molecular orbital (E(HOMO)) for anti
      inflammatory 4,5-diarylpyrroles which have been shown to have inhibitory activity
      on cyclooxygenase COX-2, an inducible enzyme expressed during inflammation. We
      have found a correlation between the E(HOMO) of a molecule and its COX-2
      inhibition. However, no correlation was observed between E(HOMO) and the
      inhibition efficiency of cyclooxygenase-1 (COX-1), the constitutively expressed
      enzyme, protective to the organism. This result suggests that the inhibitions of
      the two isoforms follow different molecular mechanisms.

PMID- 10938461
TI  - Synthesis and EPR investigations of new aminated hypocrellin derivatives.
AB  - Hypocrellins are novel photodynamic agents. A recent advance in the synthesis of
      hypocrellin congeners results in the production of two amino-substituted
      hypocrellin B derivatives in high yield via photochemical reaction. Both
      compounds exhibit similar photodynamic activity as hypocrellin B in terms of type
      I and type II mechanisms. In anaerobic media, semiquinone anion radicals can be
      detected by electron paramagnetic resonance (EPR) under irradiation; while
      superoxide anion radical, hydroxyl radical and singlet oxygen are photoproduced
      when oxygen was present. The quantum yields of singlet oxygen by these two new
      compounds are determined to be 0.72 and 0.64, respectively, similar to that of
      hypocrellin B. The comparison of the photosensitization chemistry of compounds 1
      and 2 in liposomes with that in homogeneous solution has also been made. In
      liposomes, the type II photoprocess was favored and predominant over the type I
      photoprocess due to the decreased interactions between dye molecules. Both
      compounds exhibit much stronger red light absorption than the parent hypocrellin
      and therefore, merit investigation as photosensitizers.

PMID- 10938462
TI  - Hydrogen peroxide release from human eosinophils on fibronectin: scopoletin
      enhances eosinophil activation.
AB  - We have examined the release of H(2)O(2) from PAF or TNFalpha-stimulated human
      eosinophils on fibronectin (FN)-coated polystyrene plates. H(2)O(2) release was
      measured by the standard scopoletin-horseradish peroxidase (SCOP-HRP) method and
      compared with that measured by a new microplate fluorescent assay for H(2)O(2)
      using a novel HRP substrate A6550. We observed that the SCOP-HRP method gave a 25
      fold higher estimate of H(2)O(2) release from eosinophils than did the A6550-HRP
      method. Microscopic examination of PAF or TNFalpha-stimulated eosinophils in
      buffer alone or A6550-HRP reaction mixture showed that the cells remained
      generally round, while eosinophils in SCOP-HRP reaction mixture were spread on
      the fibronectin-coated surface. Measurement of the cellular ATP content after PAF
      stimulation showed that only eosinophils activated in SCOP-HRP had a 50% fall in
      ATP content. This supported our conclusion that measurement of H(2)O(2) release
      from eosinophils in SCOP-HRP reaction mixture is problematic since the SCOP-HRP
      system activates eosinophils. However, we also found that A6550-HRP, when present
      throughout the incubation, resulted in a lower estimate of H(2)O(2) release than
      expected. The method used to detect eosinophil H(2)O(2) release greatly
      influences the absolute amount of H(2)O(2) detected.

PMID- 10938465
TI  - Production of high purity (94m)Tc for positron emission tomography studies.
AB  - The radioisotope (94m)Tc (T(1/2) = 52.5 min; I(beta)+ = 72%; E(beta)+ = 2.47 MeV)
      is of considerable interest for quantitative biodistribution studies of Tc
      radiopharmaceuticals using positron emission tomography. The nuclear processes
      (94)Mo(p,n), (93)Nb((3)He, 2n), (92)Mo(alpha,pn), and (92)Mo(alpha,2n)(94)Ru -->
      (94m)Tc are of potential interest for the production of (94m)Tc. Detailed cross
      section and yield measurements showed that the (94)Mo(p,n)-reaction over the
      energy range E(p) = 13 --> 7 MeV is most suitable: The yield of (94m)Tc is high
      (2 GBq/muAh), the impurity level is low (provided highly-enriched (94)Mo is used
      as target material), and a small-sized cyclotron is adequate. Using conventional
      targetry, sufficient quantities of the radioisotope can be produced. The chemical
      processing methods employed include both solvent extraction and
      thermochromatography. The quality of the final product is discussed.

PMID- 10938463
TI  - Reduction of oxidative stress and cytokine-induced neutrophil chemoattractant
      (CINC) expression by red wine polyphenols in zinc deficiency induced intestinal
      damage of rat.
AB  - Consumption of red wine has been associated with health promotion and disease
      prevention. We have previously found that the intestine of zinc-deficient (ZD)
      rats develop oxidative damage associated with inflammation. Here we have used
      this model to investigate whether red wine polyphenols could protect against
      intestinal injury and, if so, whether this protection was achieved through
      antioxidant and anti-inflammatory activity. The intestinal alterations induced by
      zinc deficiency such as morphological damage, increased TBA-RS level and CuZn
      superoxide dismutase activity, and decreased glutathione peroxidase activity, did
      not develop with the administration to ZD rats of a suspension of dealcoholated
      red wine (RWS). The same treatment induced in control rats a decrease of TBA-RS
      level but also of glutathione peroxidase and catalase activity. Treatment with
      RWS to ZD rats prevented a marked mucosal macrophage and neutrophil infiltration.
      The expression of pro-inflammatory cytokines, such as tumor necrosis factor alpha
      and cytokine-induced neutrophil chemoattractant (CINC), was induced by zinc
      deficiency, whereas that of the anti-inflammatory interleukin-10 was suppressed.
      Treatment with RWS reduced CINC expression. These results report a novel activity
      of red wine polyphenols in downregulation of intestinal CINC expression, which
      likely protects cells against inflammatory processes.

PMID- 10938464
TI  - Modification of creatine kinase by S-nitrosothiols: S-nitrosation vs. S
      thiolation.
AB  - Creatine kinase is reversibly inhibited by incubation with S-nitrosothiols. Loss
      of enzyme activity is associated with the depletion of 5,5'-dithiobis (2
      nitrobenzoic acid)-accessible thiol groups, and is not due to nitric oxide
      release from RSNO. Full enzymatic activity and protein thiol content are restored
      by incubation of the S-nitrosothiol-modified protein with glutathione. S-nitroso
      N-acetylpenicillamine, which contains a more sterically hindered S-nitroso group
      than S-nitrosoglutathione, predominantly modifies the protein thiol to an S
      nitrosothiol via a transnitrosation reaction. In contrast, S-nitrosoglutathione
      modifies creatine kinase predominantly by S-thiolation. Both S-nitroso-N
      acetylpenicillamine and S-nitrosoglutathione modify bovine serum albumin to an S
      nitroso derivative. This indicates that S-thiolation and S-nitrosation are both
      relevant reactions for S-nitrosothiols, and the relative importance of these
      reactions in biological systems depends on both the environment of the protein
      thiol and on the chemical nature of the S-nitrosothiol.

PMID- 10938466
TI  - Radioiodination and astatination of octreotide by conjugation labeling.
AB  - Octreotide was coupled to 3-iodobenzoyl and 3-iodonicotinoyl moieties to obtain
      [N-(3-iodobenzoyl)-D-Phe(1)]octreotide (IBO) and [N-(3-iodonicotinoyl)-D
      Phe(1)]octreotide (INO), respectively. The IC(50) values for the binding of IBO
      and INO to CA20948 rat pancreatic tumor membranes were 0.90 and 0.13 nM,
      respectively, compared with 0.35 nM for octreotide itself. Starting from N
      succinimidyl 3-[(131)I]iodobenzoate and N-succinimidyl 5-[(131)I]iodopyridine-3-
      carboxylate, [(131)I]IBO and [(131)I]INO were prepared in overall radiochemical
      yields of 35%-50%. Likewise, ?N-(3-[(211)At]astatobenzoyl)-D-Phe(1)?octreotide
      ([(211)At]ABO) was prepared in similar yield from N-succinimidyl 3
      [(211)At]astatobenzoate. In vitro assays with AR42J rat pancreatic tumor cells
      demonstrated a higher retention of cell-internalized radioiodine activity for
      [(131)I]INO compared with [(125)I]IBO. Tissue distribution studies with both
      conjugates revealed low levels of activity in the thyroid suggesting that
      dehalogenation of these peptides was minimal.

PMID- 10938467
TI  - Delivery of the alpha-emitting radioisotope bismuth-213 to solid tumors via
      single-chain Fv and diabody molecules.
AB  - Intravenously administered anti-tumor single-chain Fv (scFv) and diabody
      molecules exhibit rapid clearance kinetics and accumulation in tumors that
      express their cognate antigen. In an attempt to fit the rate of isotope decay to
      the timing of delivery and duration of tumor retention, anti-HER2/neu CHX-A" DTPA
      C6.5K-A scFv and diabody conjugates were labeled with the alpha-particle emitter
      (213)Bi (t(1/2) = 47 min). Radioimmunotherapy studies employing 0.64, 0.35, or
      0.15 microCi of (213)Bi-labeled C6.5K-A diabody or 1.1, 0.6, or 0. 3 microCi of
      (213)Bi-labeled C6.5K-A scFv were performed in nude mice bearing early,
      established SK-OV-3 tumors. Only the 0.3 microCi dose of (213)Bi-labeled C6.5K-A
      scFv resulted in both acceptable toxicity and a reduction in tumor growth rate.
      The specificity of the anti-tumor effects was determined by comparing the
      efficacy of treatment with 0.3 and 0.15 microCi doses of (213)Bi-labeled C6.5K-A
      scFv and (213)Bi-labeled NM3E2 (an irrelevant scFv) in nude mice bearing large
      established tumors. The 0.3 microCi dose of (213)Bi on both the C6.5K-A and NM3E2
      scFvs resulted in similar anti-tumor effects (p = 0.46) indicating that antigen
      specific targeting was not a factor. This suggests that the physical half-life of
      (213)Bi may be too brief to be effectively paired with systemically-administered
      diabody or scFv molecules.

PMID- 10938469
TI  - Preparation and evaluation of samarium (III) phosphate [(153)Sm] colloid (SMPC)
      for possible therapeutic use.
AB  - A simple method of preparation of a new therapeutic colloid, samarium(III)
      phosphate-(153)Sm (SMPC), is reported involving the reaction of carrier-added
      (153)SmCl(3) with phosphoric acid. Recovery of the colloid was accomplished by
      dialysis leading to purification and a radiochemical (RC) yield of more than 90%.
      The RC purity of purified colloid formulated in isotonic phosphate buffer was
      more than 99% as assessed by paper chromatography. The product retained its RC
      purity throughout the period of stability study of 7 days. Complete retention of
      radioactivity instilled in the rabbit knee joint was observed over the study
      period of 6 days, with radioactivity in the blood being indistinguishable from
      the natural background activity. Ninety-six percent of colloidal particles were
      in the size range of 0.3-2 microm. The promising results demonstrated warrant
      further studies on SMPC for assessing the suitability for therapy.

PMID- 10938468
TI  - Intratumoral injection with [(188)Re]rhenium sulfide suspension for treatment of
      transplanted human liver carcinoma in nude mice.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies in China.
      Direct intratumoral injection of nonremovable radioactive material has been
      widely studied because it could deliver high doses of radiation to target sites
      and minimize radiation leakage to non-target organs or tissues. Thirty nude mice
      bearing SMMC 7721 human liver carcinoma were used for the biodistribution study
      after intratumoral injection of [(188)Re]rhenium sulfide suspension or sodium
      [(188)Re]perrhenate solution. Another 30 tumor-bearing mice were divided into six
      groups, four groups of which were treated with a 0.1 ml [(188)Re]rhenium sulfide
      suspension at doses of 3.7, 7.4, 18.5, 29.6 MBq by a single intratumoral
      injection. For control studies, to study the tumor inhibiting ratio, the
      remaining two groups were injected with nonradioactive rhenium sulfide suspension
      and Hanks' balanced salt solution, respectively. The injections were repeated 6
      days later. The retention percentages of radioactivity (%ID) in tumors injected
      with [(188)Re]rhenium sulfide suspension were 90.96+/-6.63%, 86.09+/-22.58% and
      87.62+/-13.97% at 1, 24 and 48 h, respectively. Tumor inhibition ratios are as
      high as 89% when the outer space of tumor (0.5-0.6 cm from center) received about
      507.6 Gy doses. Intratumoral injection of [(188)Re]rhenium sulfide suspension
      results in high tumor retention indicating this approach has strong potential for
      the treatment of hepatic carcinoma.

PMID- 10938470
TI  - A strategy for increasing the brain uptake of a radioligand in animals: use of a
      drug that inhibits plasma protein binding.
AB  - A positron-emitter labeled radioligand for the glycine-binding site of the N
      methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its
      ability to penetrate the brain in animals by simultaneous use with drugs having
      high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has
      poor blood-brain barrier (BBB) permeability because it binds tightly to plasma
      proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin
      and resembles L-703,717 in structure, dose-dependently enhanced the penetration
      by [(11)C]L-703,717 in mice, resulting in a five-fold increase in the brain
      radioactivity at 1 min after the injection. Drugs structurally unrelated to L
      703,717, salicylate, phenol red, and L-tryptophan, were less effective or
      ineffective in increasing the uptake of [(11)C]L-703,717. These results suggest
      that the simultaneous use of a drug that inhibits the binding of a radioligand to
      plasma proteins is a useful way to overcome the poor BBB permeability of the
      radioligand triggered by its tight binding to plasma proteins. In brain
      distribution studies in rodents, it was found that, after the increase in brain
      uptake with warfarin, much of the glycine site antagonist accumulates in the
      cerebellum but its pharmacological specificity did not match the glycine site of
      NMDA receptors.

PMID- 10938471
TI  - Pharmacokinetics of the thymidine analog 2'-fluoro-5-[(14)C]-methyl-1-beta-D
      arabinofuranosyluracil ([(14)C]FMAU) in rat prostate tumor cells.
AB  - 2'-Fluoro-5-[(14)C]-methyl-1-beta-D-arabinofuranosyluracil (FMAU) is an analog of
      thymidine (TdR) that is resistant to catabolism, is incorporated into DNA, and
      has been labeled with (11)C for use with positron emission tomography. We
      compared the uptake and metabolism of [(14)C]FMAU with that of [(3)H]TdR in fast-
      and slow-growing cell lines of a rat prostate tumor. Although FMAU was
      incorporated much less rapidly than TdR, FMAU behaved very similarly to TdR with
      respect to correlation between uptake velocity and cell growth rate, saturability
      of cellular incorporation, and intracellular metabolite pools. Thus, FMAU
      warrants further evaluation as an in vivo indicator of tumor cell division.

PMID- 10938472
TI  - Synthesis of a novel class of nitrido Tc-99m radiopharmaceuticals with phosphino
      thiol ligands showing transient heart uptake.
AB  - A novel class of technetium-99m radiopharmaceuticals showing high heart uptake is
      described. These complexes were prepared through a simple and efficient
      procedure, and their molecular structure fully characterized. They are formed by
      a terminal Tc(triple bond)N multiple bond and two bidentate phosphine-thiol
      ligands [R(2)P-(CH(2))(n)SH, n=2,3] coordinated to the metal ion through the
      neutral phosphorus atom and the deprotonated thiol sulfur atom. The resulting
      geometry was trigonal bipyramidal. Biodistribution studies were carried out in
      rats. The complexes exhibited high initial heart uptake and elimination through
      liver and kidneys. The washout kinetic from heart was dependent on the nature of
      the lateral R groups on the phosphine-thiol ligands. When R=phenyl, heart
      activity was rapidly eliminated within 10-20 min. Instead, when R=tolyl,
      cyclohexyl, persistent heart uptake was observed. Extraction of activity from
      myocardium tissue showed that no change of the chemical identity of the tracer
      occurred after heart uptake. On the contrary, metabolization to more hydrophilic
      species occurred in liver and kidneys.

PMID- 10938473
TI  - Labeling and in vivo evaluation of novel copper(II) dioxotetraazamacrocyclic
      complexes.
AB  - 64Cu shows promise as both a positron emission tomography imaging and
      radiotherapeutic radionuclide due to its half-life (T(1/2) = 12. 7 h), decay
      characteristics (beta(+) [19%]; beta(-) [40%]), and the capability to produce it
      on a large-scale with high specific activity on a biomedical cyclotron.
      Macrocyclic chelators are generally used as bifunctional chelators to attach
      Cu(II) to antibodies and peptides due to their relatively high in vitro
      stability. To investigate neutral Cu(II) complexes, we performed labeling
      experiments with six tetraazamacrocyclic ligands with different chelate ring
      sizes. 1,4,8,11-Tetraazacyclotetradecane-3, 9-dione (1), 1,4,8,11
      tetraazacyclotetradecane-5,7-dione (2), 1,4,7, 10-tetraazacyclotridecane-11,13
      dione (3), 1,4,7, 10-tetraazacyclotridecane-2,9-dione (4), 1,4,7, 10
      tetraazacyclododecane-2,9-dione (5), and 1,4,7, 10-tetraazacyclotridecane-3,8
      dione (6) were radiolabeled with (64)Cu. Only (64)Cu-labeled 1 readily formed a
      complex in high purity, and therefore was evaluated in vivo. The rapid blood,
      liver, and kidney clearance of (64)Cu-labeled 1 suggest that ligand 1 may be
      useful as a macrocyclic structure to design new bifunctional chelators for copper
      radionuclides in diagnostic or radiotherapeutic studies and is a potential
      alternative to currently used macrocyclic bifunctional chelators.

PMID- 10938474
TI  - Synthesis and evaluation of 6-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as
      a PET tracer for nicotinic acetylcholine receptors.
AB  - Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)
      2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non
      opioid analgesic properties, have high affinity for neuronal nicotinic
      acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of
      epibatidine. 6-[(18)F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[(18)F]fluoro
      A-85380), a F-18 labeled analogue of these two compounds, is therefore a
      promising radioligand for positron emission tomography (PET) studies in humans.
      The use of trimethylammonium as a leaving group in nucleophilic aromatic
      substitution reactions has proven to be a versatile and efficient strategy, and
      offers several advantages over other leaving groups. Here, we report the
      synthetic strategy for the preparation of a precursor, as a trimethylammonium
      iodide salt, and its use in the radiosynthesis to 6-[(18)F]fluoro-A-85380.
      Preliminary compartative PET studies of 6-[(18)F]fluoro-A-85380 and 2
      [(18)F]fluoro-A-85380 were carried out in baboon to examine their suitability as
      tracers for studying nAChR system.

PMID- 10938475
TI  - The development of (99m)Tc-analog of Cu-DTS as an agent for imaging hypoxia.
AB  - Works on dithiosemicarbazone (DTS) derivatives radiolabeled with divalent Cu (Cu
      62, Cu-64) indicate its potentiality as an ischemic tissue detecting agent.
      Development of analogous derivatives labeled with the more accessible technetium
      99m (Tc) is most desirable. Various synthesized DTS derivatives are radiolabeled
      with a novel approach, using a macromolecular Sn(II)-complex under an anaerobic
      condition at pH 3.4-4.5 and stabilization by ascorbate solution at pH 6.7-7.0.
      Characterization of Tc-DTS derivatives done by various analytical methods (TLC,
      HPLC, EP, PC) and by in vivo studies in normal mice and in rats myocardial LAD
      (left anterior descent coronary artery) occlusion model. Among tested DTS, only
      Tc-ATSE, Tc-ATSM and Tc-ATSM(2) showed distinctive characteristics, with the
      latter presenting high myocardium uptake in regions of ischemia in LAD rat
      myocardium model. Potentiality of the Cu-DTS mimetic agent, Tc-ATSM(2) as an
      ischemia-damaged myocardium agent is discussed.

PMID- 10938476
TI  - A PET study of adenosine A1 receptor in anesthetized monkey brain.
AB  - We demonstrated the distribution of adenosine A1 receptors in the anesthetized
      monkey brain with positron emission tomography (PET) using [(11)C]KF15372 ([1
      propyl-(11)C]8-dicyclopropylmethyl-1, 3-dipropylxanthine). [(11)C]KF15372 was
      injected intravenously. The regional standardized uptake values and the
      distribution volume were calculated. We also investigated the effect of carrier
      on the uptake and regional brain distribution of [(11)C]KF15372. The use of
      [(11)C]KF15372 with dynamic PET scanning could be an appropriate method to
      analyze the regional binding potential of adenosine A1 receptors in living brain.

PMID- 10938477
TI  - Imaging Tc-99m-labeled FGF-1 targeting in rats.
AB  - Recombinant human acidic fibroblast growth factor (FGF-1) was radiolabeled with
      (99m)Tc by the HYNIC method. The (99m)Tc-FGF-1 retained its representative
      molecular mass, heparin affinity, cellular binding to both low (Kd = 9.5 nM) and
      high (Kd = 125 pM) affinity sites, and mitogenic activity. Gamma camera imaging
      after intravenous dosing in rats confirmed high liver and kidney binding. Heparin
      significantly decreased (99m)Tc-FGF-1 liver uptake and increased urinary
      excretion. These studies illustrate a new method for imaging FGF-1 targeting
      under various conditions.

PMID- 10938478
TI  - Synthesis and in vivo evaluation of (E)-N-[(11)C]Methyl-4- (3-pyridinyl)-3-butene
      1-amine ([(11)C]metanicotine) as a nicotinic receptor radioligand.
AB  - (E)-N-[(11)C]Methyl-4-(3-pyridinyl)-3-butene-1-amine ([(11)C]metanicotine), a
      high affinity (K(i) = 16 nM) CNS-selective nicotinic agonist, was prepared by the
      [(11)C]alkylation of the desmethyl precursor with [(11)C]methyl
      trifluoromethanesulfonate. In vivo distribution studies in mice demonstrated good
      blood brain permeability but essentially uniform regional brain distribution and
      no evidence of specific binding to nicotinic cholinergic receptors. Identical
      results were obtained in an imaging study performed in a monkey brain. Therefore,
      despite literature reports supporting the use of metanicotine as a cognition
      enhancing nicotinic agonist, (E)-N-[(11)C]methyl-4-(3-pyridinyl)-3-butene-1-amine
      does not appear to be a suitable candidate for in vivo imaging studies of
      nicotinic acetylcholine receptors in the mammalian brain.

PMID- 10938479
TI  - Evaluation of (99m)Tc-labeled photosan-3, a hematoporphyrin derivative, as a
      potential radiopharmaceutical for tumor scintigraphy.
AB  - A quick and reproducible method for radiolabeling of Photosan-3(R), a
      photosensitizer used worldwide for photodynamic therapy (PDT) of cancer, with
      radioisotope of technetium ((99m)Tc) was developed. The radiotracer was evaluated
      for radiochemical purity, stability, and tissue distribution in a murine tumor
      model. The (99m)Tc-Photosan-3, which was prepared by using (99m)Tc-pertechnetate
      in place of reduced (99m)Tc, demonstrated better labeling efficiency (>90%) and
      reproducibility. The procedure also minimized radiation exposure to the
      radiochemist because handling time was considerably reduced. Due to the
      commercial availability of Photosan-3, the risk of batch-to-batch variation in
      the in situ synthesis of hematoporphyrin derivative, which is a complex mixture
      of at least five compounds, was also significantly reduced. The biodistribution
      studies and tumor scintigraphy confirmed that (99m)Tc-labeled Photosan-3 was
      preferentially taken up by the neoplastic tissue similar to the parent compound.
      In addition to its applications in tumor imaging, (99m)Tc-Photosan-3 could also
      be used for estimating tumor uptake of Photosan-3 as may be required for
      individualization of clinical protocols of PDT.

PMID- 10938480
TI  - Importance of neuroendocrine activation in chronic heart failure. Impact on
      treatment strategies.

PMID- 10938481
TI  - Angiotensin II antagonists are superior to ACE inhibitors; David vs. Goliath.

PMID- 10938482
TI  - 'ACE inhibitors are better than AT(1) receptor blockers (ARBs)' - controversies
      in heart failure.

PMID- 10938483
TI  - The role of cardiovascular magnetic resonance in heart failure.
AB  - Cardiovascular Magnetic Resonance (CMR) is an accepted gold standard for non
      invasive, accurate, and reproducible assessment of cardiac mass and function. The
      interest in its use for viability, myocardial perfusion and coronary artery
      imaging is also widespread and growing rapidly as the hardware and expertise
      becomes available in more centres, and the scans themselves become more cost
      effective. In patients with heart failure, accurate and reproducible serial
      assessment of remodelling is of prognostic importance and the lack of exposure to
      ionizing radiation is helpful. The concept of an integrated approach to heart
      failure and its complications using CMR is fast becoming a reality, and this will
      be tested widely in the coming few years, with the new generation of dedicated
      CMR scanners.

PMID- 10938484
TI  - Angiotensin converting enzyme (ACE) gene expression in the human left ventricle:
      effect of ACE gene insertion/deletion polymorphism and left ventricular function.
AB  - AIMS: We investigated the effect of the angiotensin converting enzyme (ACE) I/D
      polymorphism and left ventricular (LV) function on ACE gene expression in tru-cut
      LV myocardial biopsies from 50 consecutive patients (II: 18, ID: 18, DD: 14; 40
      males) with ischaemic heart disease undergoing coronary artery bypass grafting
      (CABG). METHODS: The polymerase chain reaction was used for ACE genotyping. LV
      function [normal (n=22) or impaired] was determined by left ventriculography at
      cardiac catheterisation prior to bypass surgery. ACE expression was determined
      (n=46) by a competitive quantitative reverse transcription PCR assay using
      5x10(5), 12. 5x10(5) and 20x10(5) copies of a mutant DNA internal standard (IS).
      PCR products were analysed by negative film photography and laser densitometry to
      determine the number of ACE transcripts present. RESULTS: Mean age was similar
      (II: 59.1+/-10.4, ID: 57.0+/-10.6, DD: 61.4+/-6.2; P=NS) with no differences
      between groups in sex (P=0. 25); hypertension, P=0.31; previous myocardial
      infarction, P=0.44; LV function, P=0.23; and ACE inhibitor therapy, P=0.06. ACE
      expression per 100 ng of total RNA varied with genotype [<5x10(5) copies in II:
      6, 5-12.5x10(5) copies in II: 6, ID: 16, DD: 4; and >12.5x10(5) (II: 4, ID: 2,
      DD: 8), Kendall's tau-b coefficient (tau(b))=0.43, P=0.003]. Impaired LV function
      also correlated with higher levels of ACE expression, Kendall's tau(b)=0.40,
      P=0.001. CONCLUSION: ACE gene expression in the left ventricle varied with ACE
      genotype and LV function in IHD patients undergoing CABG.

PMID- 10938485
TI  - Pentoxifylline-augmented antiproliferative effects of adrenomedullin on vascular
      smooth muscle cells.

PMID- 10938486
TI  - Catecholamine levels in heart failure due to dilated cardiomyopathy and their
      relationship to the severity of heart failure.

PMID- 10938487
TI  - QT interval lengthening in cardiac disease relates more to left ventricular
      systolic dysfunction than to autonomic function.
AB  - BACKGROUND: There are multiple influences on the QTc interval, including the
      autonomic nervous system. Which influence is the principal determinant of the
      variation in QTc interval between different cardiac diseases is not yet clear,
      though some studies have suggested that the QTc interval primarily reflects
      sympatho-vagal balance. This study investigated this claim further. AIM: To
      determine if autonomic tone was the prime determinant of variation in the QTc
      interval between subjects with different cardiac diseases. METHODS: Subjects with
      different cardiac diseases were studied, QTc interval determined and correlated
      with three different measures of the autonomic nervous system, that of baroreflex
      sensitivity, catecholamine levels (epinephrine and norepinephrine) and sympatho
      vagal balance as determined by power spectrum analysis. RESULTS: 47 subjects were
      studied, comprising 17 subjects with heart failure, 14 subjects with left
      ventricular hypertrophy and 16 control subjects. For the group as a whole there
      was no relationship between QTc interval and any measure of the autonomic nervous
      system function, but there was a reasonable relationship between fractional
      shortening and QTc interval (r=0.47, P<0.003). For subjects with an
      echocardiographic fractional shortenings less than 0.35 (which correlates with an
      ejection fraction of <50%), a strong relationship between fractional shortening
      and QTc interval remained (r=0.57, P<0.002), but in addition a relationship
      between QTc interval and catecholamine levels developed (for epinephrine: r=0.67,
      P<0.002; and for norepinephrine: r=0.62, P<0.005). Multiple regression analysis
      showed that fractional shortening and epinephrine levels were independently
      related to QTc interval. CONCLUSION: In subjects with a variety of cardiac
      diseases, the prime determinant of QTc interval is left ventricular systolic
      performance rather than the autonomic nervous system, though in subjects with low
      normal and less fractional shortenings catecholamine levels are independently
      related to QTc interval.

PMID- 10938488
TI  - Comparison of different methods of functional evaluation in patients with chronic
      heart failure.
AB  - BACKGROUND: Stratification of the severity of heart failure has major prognostic
      and therapeutic implications. AIMS: To prospectively compare different methods of
      assessment of functional capacity in patients with chronic heart failure (CHF).
      METHODS AND RESULTS: We studied 143 patients (78 male and 65 female) with CHF
      aged less than 70 years (mean 57.3 years). Functional assessment was made
      clinically according to NYHA classification and according to the Goldman Activity
      Scale Classification (GASC). Cardiovascular performance was measured by peak O(2)
      consumption (pVO(2)) and anaerobic threshold (AT) at cardiopulmonary exercise
      test and by the distance walked during a 6-min walk test (6-MWT). Clinical scales
      resulted significantly related. Peak VO(2) and AT showed a mild relation with
      distance covered at 6-MWT (r=0.56 and r=0.46, respectively). Concordance between
      NYHA classification and levels of performance at cardiopulmonary exercise test or
      at 6-MWT was less than 50%. CONCLUSION: Our results suggest that none of the
      usually employed methods give a definitive assessment of functional capacity of
      cardiovascular system and a high degree of discordance exists among the results
      of different tests in the same patient. Although NYHA classification maintains
      its value in clinical evaluation of patients with CHF, the 6-min walk test is
      recommended in patients with mild-to-moderate CHF (II-III NYHA classes) as a
      simple and useful screening test to select patients for further diagnostic
      evaluation.

PMID- 10938489
TI  - Does in-patient ECG monitoring have an impact on medical care in chronic heart
      failure patients?
AB  - BACKGROUND: Heart failure patients' management in non-intensive care units might
      be improved by telemetry monitoring. However, telemetry adds the cost and
      evidence of this effectiveness is not available. AIM: To evaluate the utility of
      the ECG monitoring in chronic heart failure patients admitted to a non-intensive
      care unit. METHODS: A prospective analysis of the utility of telemetry in 711
      patients admitted to a Heart Failure Unit from March 1996 to September 1997.
      RESULTS: One hundred and ninety-nine patients underwent telemetry; 108 telemetry
      findings were recorded, in 35% of NYHA class II, in 46% in NYHA class III-IV and
      43% in unstable patients. Reasons for telemetry were: known arrhythmia (n=82),
      electrolytes disturbances (n=20), atrial fibrillation (n=12), symptoms (n=48),
      i.v. dobutamine (n=13), drugs control (n=16), devices control (n=8). Crossing
      reasons for telemetry and detected events we had, respectively, 63, 11, 2, 17, 5,
      6, and 0 telemetry findings. Treatment was guided by telemetry results in only 33
      cases (respectively in 18, 0, 4, 5, 5, 1, and 0 cases). Physicians perceived
      telemetry as unhelpful in 30% of cases; as helpful in 70%. The percentage of
      inutility, usefulness with and without related medical intervention were similar
      between stable and unstable patients (30, 18, 51% and 31, 15, 54%, respectively).
      CONCLUSION: In a heart failure unit ECG monitoring is mostly used in severe and
      unstable patients. However, medical decisions are rarely guided by the telemetry
      findings. The usefulness of telemetry might be underestimated because one of the
      uncounted results might be the avoidance of inappropriate intervention.

PMID- 10938490
TI  - Experience of commencing Carvedilol in elderly patients with heart failure in a
      routine outpatient clinic.
AB  - Carvedilol has been shown to be beneficial for patients with heart failure, but
      it is not clear how it should be initiated in routine clinical practice,
      particularly in the elderly. This study is a retrospective review of 19 patients
      of age 80+/-4 years with heart failure, who had Carvedilol treatment initiated in
      a routine outpatient clinic. No patient experienced a worsening of their heart
      failure or required admission to hospital. There was a mean reduction in heart
      rate of 11 beats/min. Carvedilol was tolerated by 68% of the patients. Thus,
      Carvedilol can be safely initiated in a routine outpatient clinic in
      appropriately selected elderly patients.

PMID- 10938491
TI  - Health care costs of heart failure: results from a randomised study of patient
      education.
AB  - BACKGROUND: Heart failure is a serious syndrome with a bad prognosis.
      Hospitalisation is common and readmittance rate is high; factors which influence
      the cost of care and treatment. Only scarce data on detailed patient materials
      regarding health care costs are known. AIMS: To describe in detail the health
      care costs for heart failure patients. METHODS: Costs for patients (n=108) who
      completed a randomised education trial were studied for 6 months after hospital
      discharge. Costs for hospital stay, out-patient visits, diagnostic tests and
      procedures, laboratory analyses and drug treatment were calculated. Official unit
      prices list used to reimburse providers of cross-boundary health services and
      prices for drugs in the Swedish Drug Compendium were employed. RESULTS: The total
      cost for a heart failure patient was approximately 20000 SEK (2564 US$, 7.80
      SEK=1 US$) for 6 months. There was a 27-fold variation between patients. There
      was no relation between age or sex and cost. In decreasing order cost for
      hospitalisation was followed by costs for out-patient visits, diagnostic tests
      and procedures, laboratory analyses and drugs. CONCLUSION: Hospitalisation was
      the largest part of the total cost and there was a large inter-individual
      variation. Efforts to reduce the economic burden should be focused on
      hospitalisation. Due to skewed distribution, individual data must be considered
      in the analysis of the efforts.

PMID- 10938492
TI  - First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in
      chronic heart failure: a comparison of enalapril and perindopril. Slovak
      Investigator Group.
AB  - BACKGROUND: First-dose hypotension refers to an observed reduction in blood
      pressure after the administration of the first dose of ACE inhibitors in patients
      with congestive heart failure. AIM: To compare the first-dose responses of low
      dose enalapril and perindopril in patients with stable symptomatic chronic heart
      failure. METHODS: Single blind, randomised, multicenter, parallel, prospective
      study. Patients (N=298) with chronic heart failure due to ischemic heart disease
      or dilated cardiomyopathy, NYHA II-IV, ejection fraction<40%, age>18 years, naive
      to ACE inhibitors or ATI-receptor blocker, were randomised to receive a single
      dose of 2. 5 mg enalapril or 2.0 mg perindopril. Baseline laboratory and clinical
      examinations were performed before entry into the study. Ambulatory blood
      pressure monitoring started 2 h before the study medication was given, and
      continued for at least 10 h after the medication. RESULTS: The maximum drop in
      blood pressure appeared approximately 4 h after dose administration in both
      groups, and was more pronounced in the enalapril group. Patients in the enalapril
      group had a significantly higher incidence of asymptomatic hypotension. No
      symptomatic hypotension requiring a change in medication or a prolongation of
      hospitalisation was observed. CONCLUSION: A low dose of perindopril is well
      tolerated at initiation of ACE inhibitor therapy in patients with chronic heart
      failure and causes less first-dose hypotension than a low dose of enalapril.

PMID- 10938493
TI  - Effects of high-dose furosemide and small-volume hypertonic saline solution
      infusion in comparison with a high dose of furosemide as a bolus, in refractory
      congestive heart failure.
AB  - BACKGROUND: Diuretics, have been accepted as first-line treatment in refractory
      heart failure, but a lack of response is a frequent event. A randomised single
      blind study was performed to evaluate the effects of the combination of high-dose
      furosemide and small-volume hypertonic saline solution (HSS) infusion in the
      treatment of refractory NYHA class IV congestive heart failure (CHF). MATERIALS
      AND METHODS: Sixty patients (21 F/39 M) with refractory CHF (NYHA class IV) of
      different etiologies, unresponsive to high oral doses of furosemide, ACE
      inhibitors, digitalis, and nitrates, aged 65-90 years, were enrolled. They had to
      have an ejection fraction (EF) <35%, serum creatinine <2 mg/dl, BUN </=60 mg/dl,
      a reduced urinary volume and a low natriuresis. The patients were randomised in
      two groups (single blind): group 1 (11 F/19 M) received an i.v. infusion of
      furosemide (500-1000 mg) plus HSS (150 ml of 1.4-4.6% NaCl) b.i.d. in 30 min.
      Group 2 (10 F/20 M) received an i.v. bolus of furosemide (500-1000 mg) b.i.d.,
      without HSS, during a period lasting 6-12 days. Both groups received KCl (20-40
      mEq.) i.v. to prevent hypokalemia. All patients underwent at entry a physical
      examination, measurement of body weight (BW), blood pressure (BP), heart rate
      (HR), evaluation of signs of CHF, and controls of serum Na, K, Cl, bicarbonate,
      albumin, uric acid, creatinine, urea and glycemia and daily during
      hospitalization, as well as the daily output of urine for, Na, K and Cl
      measurements. Chest X-ray, ECG and echocardiogram were obtained at entry during
      and at the discharge. During the treatment and after discharge the daily dietary
      Na intake was 120 mmol with a drink fluid intake of 1000 ml daily. An assessment
      of BW and 24-h urinary volume, serum and urinary laboratory parameters, until
      reaching a compensated state, were performed daily, when i.v. furosemide was
      replaced with oral administration (250-500 mg/day). After discharge, patients
      were followed as outpatients weekly for the first 3 months and subsequently once
      per month. RESULTS: The groups were similar for age, sex, EF, risk factors,
      treatment and etiology of CHF. All patients showed a clinical improvement. Six
      patients in both groups had hyponatremia (from 120 to 128 mEq./l) at entry. A
      significant increase in daily diuresis in both groups was observed (from 390+/
      155 to 2100+/-626, and from 433+/-141 to 1650+/-537 ml/24 h, P<0.05). Natriuresis
      (from 49+/-15 to 198+/-28 mEq./24 h) was higher in group 1 vs. group 2 (from
      53.83+/-12 to 129+/-39 mEq./24 h, P<0.05). Serum Na (from 135.9+/-6.8 to 142.2+/
      3. 8 mEq./l, P<0.05) increased in the group 1 and decreased in the group 2 (from
      134.7+/-7.9 to 130.1+/-4.3 mEq./l). Serum K was decreased (from 4.4+/-0.6 to
      3.9+/-0.6, and 4.6+/-9 to 3.6+/-0.5 mEq. /l, P<0. 05) in both groups. BW was
      reduced (from 73.8+/-9.1 to 63. 8+/-8.8, and from 72.9+/-10.2 to 64.5+/-7.5 kg,
      P<0. 05) in both groups. Group 2 showed more patients in NYHA class III than
      group 1 (18 vs. 2 patients, P<0.05). Group 2 showed an increase of serum
      creatinine. Serum uric acid increased in both groups. BP values decreased, and HR
      was corrected to normal values in both groups. Group 2 showed a longer
      hospitalization time than group receiving HHS infusion (11.67+/-1.8 vs. 8.57+/
      2.3 days, P<0.001). In the follow-up (6-12 months), none of the patients from
      group 1 were readmitted to the hospital and they maintained the NYHA class
      achieved at the discharge. Group 2 showed 12 patients readmitted to hospital and
      a higher class than at discharge. CONCLUSION: Our data suggest that the
      combination of furosemide with HSS is feasible and it appears that this
      combination produces an improvement of hemodynamic and clinical parameters,
      reduces the hospitalization time and maintains the obtained results over time in
      comparison with those receiving high-dose furosemide as bolus.

PMID- 10938494
TI  - Screening, endpoint classification, and safety monitoring in the Metoprolol CR/XL
      Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF).
AB  - The MERIT-HF study was designed to investigate the effect of once-daily dosing of
      metoprolol succinate CR/XL added to standard therapy in patients with chronic
      heart failure. A screening programme, aiming at identifying eligible patients for
      the study was used by 231 out of 313 sites, resulting in 8912 screened patients.
      These patients were older, more often women, had marginally higher ejection
      fraction and were more often in NYHA class IV compared to the finally randomised
      patients. There was a positive correlation between the number of screened and
      randomised patients and due to the high inclusion rate the number of randomised
      patients was increased from 3200 to 3991 patients. The clinical events were
      defined by a manual and were based on identical classifications made
      independently by two members of an Independent Endpoint Committee. Data from the
      case report form and the classifications made by the Endpoint Committee were in
      accordance for hospitalisation due to worsening heart failure on 722 occasions.
      On 207 occasions the data from the case report forms and the classification made
      by the committee differed regarding this clinical event. The Independent Safety
      Committee monitored safety aspects of the study by using asymmetric group
      sequential procedures. The study was stopped early on recommendation from the
      Independent Safety Committee, when the second pre-specified interim analysis (50%
      of total number of expected deaths) showed that the criterion for stopping due to
      benefit had been met and exceeded. In conclusion, a screening programme
      facilitated patient recruitment and showed the characteristics of the background
      population, the event classification was improved by using an independent
      endpoint committee, and the safety monitoring allowed an early closure of the
      study due to mortality benefit, without jeopardising the final analyses of the
      results.

PMID- 10938495
TI  - Design and methodology of the CAPRICORN trial - a randomised double blind placebo
      controlled study of the impact of carvedilol on morbidity and mortality in
      patients with left ventricular dysfunction after myocardial infarction.

PMID- 10938496
TI  - Are beta-blockers effective in patients who develop heart failure soon after
      myocardial infarction? A meta-regression analysis of randomised trials.
AB  - BACKGROUND: The great majority of post-infarction studies of beta-blockers were
      conducted in an era when these agents were widely held to be contra-indicated for
      the management of heart failure. We now know that beta-blockers are highly
      effective for the management of patients with chronic stable heart failure.
      However, there remains uncertainty about their role in the setting of post
      infarction heart failure and ventricular dysfunction. AIM: the primary objective
      in this paper, was to investigate the extent to which heart failure or evidence
      of major cardiac dysfunction influenced outcome in previous trials of beta
      blockers in heart failure after myocardial infarction. METHODS: We assessed the
      extent to which the inclusion of patients with heart failure or major cardiac
      dysfunction influenced outcome in randomised trials of long-term use of beta
      blockade after myocardial infarction. The primary analysis was to assess the
      extent to which the proportion of patients included in each trial with heart
      failure influenced the relative odds of all-cause mortality in the trials. All
      randomised trials without crossover with treatment lasting more than one month
      and with 50 or more patients were considered. All those that provided information
      on the proportion of patients with heart failure or major cardiac dysfunction in
      the original or subsequent articles were included in the analysis. RESULTS:
      Overall treatment with a beta-blocker was associated with a 22.6% reduction in
      the odds of death (95% C1 11-32.3%). There were very few data on the effects of
      beta-blockers after myocardial infarction in patients with documented left
      ventricular systolic dysfunction. In the analysis that included heart failure as
      a factor, treatment with a beta-blocker was associated with a non-significant
      interaction with the presence of heart failure. However, because the group
      including heart failure patients were at higher risk, the absolute benefit of
      treatment with beta-blockers appeared greater in this group. CONCLUSIONS: This
      analysis suggests that the relative benefit of beta-blockers on mortality after a
      myocardial infarction is similar in the presence or absence of heart failure but
      that the absolute benefit may be greater in the former. However, as current
      clinical practice has changed radically from the time when the majority of these
      trials were conducted, further trial evidence would be desirable.

PMID- 10938497
TI  - The management of heart failure in Spain.

PMID- 10938498
TI  - How patients with heart failure are managed in Georgia.

PMID- 10938499
TI  - The emerging management of viral hepatitis

PMID- 10938500
TI  - Canadian consensus conference on the management of viral hepatitis. Canadian
      Association for the Study of the Liver.
AB  - These proceedings of a consensus conference on the management of viral hepatitis
      were sponsored by the Canadian Association for Study of the Liver (CASL) and
      Health Canada. Experts in various aspects of viral hepatitis presented a review
      of the medical literature on assigned topics. Three expert panels were convened;
      they debated assigned topics, which corresponded to the reviews presented
      earlier. Attempts were made to reach consensus on a number of recommendations
      about the management of viral hepatitis. The content of the literature reviews,
      the debates and consensus statements were synthesized into a preliminary
      document. The report gives some background and offers recommendations aimed at
      both the general practitioner and the specialist.

PMID- 10938501
TI  - Outcomes research in chronic viral hepatitis C: effects of interferon therapy.
AB  - Although chronic hepatitis C (CHC) is often mild and asymptomatic, it may lead to
      decompensated hepatic cirrhosis and death. CHC is now the single most important
      indication for liver transplantation in North America. CHC is also an important
      cause of morbidity. Recent work is reviewed and shows that the health-related
      quality of life (HRQOL) of patients with CHC is markedly reduced compared with
      that of age- and sex-matched controls. For as yet unknown reasons, this reduction
      is more severe in CHC patients than in those with chronic hepatitis B. Successful
      therapy of CHC with type 1 interferons (IFNs) leads to substantial improvement -
      to nearly normal levels - in patients' HRQOL. In addition, IFN or IFN plus
      ribavirin therapy for CHC is highly cost effective, despite its limited long term
      efficacy; estimates of the costs to gain one year of quality-adjusted life range
      from no cost (that is, therapy is cost saving) to US$11,400 (for those most
      difficult to cure). Thus, despite the limited effectiveness of current therapies
      for CHC, they are fully justified based on their beneficial effects on patients'
      HRQOL and their cost effectiveness.

PMID- 10938502
TI  - Early changes in hepatitis C virus (HCV) RNA levels predict response to
      interferon treatment in noncirrhotic HCV patients.
AB  - The role of hepatitis C virus (HCV) RNA quantification in determining ideal
      interferon (IFN) treatment of noncirrhotic HCV liver disease is uncertain. The
      specific aim of this study was to determine whether measurement of baseline HCV
      RNA or changes in HCV RNA levels (DHCV RNA) early during therapy predict response
      to IFN alpha in noncirrhotic HCV patients. PATIENTS AND METHODS: Twenty-one
      noncirrhotic patients with chronic HCV were treated with 3 MU IFN alpha-2a three
      times per week. HCV RNA levels were determined at baseline and after two, four,
      six, eight and 12 weeks of treatment. Baseline HCV RNA and DHCV RNA during
      therapy were compared with treatment response results at six months. Data were
      expressed as mean +/- SE, and differences were assessed using Student's t test.
      RESULTS: Twenty-one patients initiated IFN alpha therapy. Two patients were
      noncompliant and lost to follow-up. One patient discontinued IFN alpha due to
      side effects. Apart from age, where responders tended to be younger than
      nonresponders, the baseline clinical characteristics and alanine aminotransferase
      (ALT), aspartate aminotransferase, bilirubin and HCV RNA levels did not differ
      between IFN alpha responders and nonresponders. Levels of HCV RNA were
      significantly lower after both two and four weeks of therapy in IFN alpha
      responders compared with nonresponders (P<0.001). Changes in log HCV RNA levels
      after both two and four weeks of therapy were significantly greater in IFN alpha
      responders compared with nonresponders (P<0.001). Changes in log HCV RNA of more
      than 1.0 after two weeks of IFN alpha therapy identified all six-month
      responders, with a sensitivity of 100% and a specificity of 89%. Potential
      financial impact of these findings on patients' management was also calculated.
      Decisions regarding discontinuation of therapy based on early changes in HCV RNA
      levels would result in a 40% to 50% reduction in IFN alpha cost. CONCLUSIONS: In
      noncirrhotic HCV patients, the change in quantitative HCV RNA after the first two
      weeks of IFN alpha therapy identifies responders. This finding would result in a
      40% to 50% cost savings if decisions about continuing IFN alpha were based on
      early changes in HCV RNA levels rather than ALT or HCV RNA assessment after the
      completion of three months of IFN alpha treatment.

PMID- 10938503
TI  - A Canadian isolate of hepatitis D (delta) virus.
AB  - Hepatitis D (delta) virus (HDV) is an infectious agent that propagates in
      hepatocytes only in the presence of hepatitis B virus, causing fulminant or
      chronic hepatitis with liver cirrhosis. HDV is a 36 nm particle that includes a
      circular RNA genome of 1.7 kilobases with an extensive internal complementary
      that allows it to fold into a rod-like structure. The relationships among
      genotypes, sequence variability, geographical distribution and disease severity
      of HDV remain unknown. Consequently, in the present study, the complete
      nucleotide sequence of an HDV isolated from a Canadian patient was determined.
      The viral RNA from serum was amplified using reverse transcription coupled to
      polymerase chain reaction amplification. The resulting complementary DNA was
      cloned and sequenced. Sequence analysis revealed that this new isolate contained
      1672 nucleotides corresponding to genotype 1, which has a worldwide distribution.
      Sequencing of four independent clones revealed 17 substitutions, corresponding to
      an overall sequence variability of 1%. Surprisingly, seven mutations were found
      in the 48-nucleotide region located between the two highly conserved self
      catalytic motifs. This is the first demonstration that many substitutions are
      identified in this region of HDV, and prompts the present authors to define it as
      a hypervariable region.

PMID- 10938504
TI  - Treatment of hepatitis C virus infection in children.
AB  - Hepatitis C virus (HCV) infection is the most common cause of chronic liver
      disease in the western world. Despite extensive epidemiological data in adults,
      the exact number of children infected is still unknown, and little is known about
      the natural history of chronic HCV infection in childhood. The authors review
      studies focusing on HCV infection in children, and summarize the results,
      including the efficacy of interferon, and interferon plus ribavirin combination
      treatment of HCV hepatitis in childhood.

PMID- 10938505
TI  - Why and how to treat chronic hepatitis C.
AB  - Chronic hepatitis C (CHC) is a major health problem worldwide, with approximately
      200 million affected individuals and a significant rate of progression to end
      stage cirrhosis and hepatocellular carcinoma (HCC). If hepatitis C virus (HCV)
      infection is left untreated in the population, then the number of liver-related
      deaths will soon double and the need for liver transplantation may increase to
      five times that seen today. Available therapies for CHC are restricted to
      interferon alpha (IFN alpha) monotherapy and to the combination of IFN alpha and
      ribavirin. Despite their high cost and side effects, both of these therapies have
      proved to be cost effective, particularly combination therapy. IFN alpha
      monotherapy for one year can induce sustained response (SR) rates of
      approximately 10% in naive patients infected with HCV genotype 1, and above 50%
      in those infected with other genotypes. Combination therapy can double or even
      triple the rate of SR in genotype 1 infections and may further increase the SR
      rate in the other HCV genotypes. Combination therapy has also been proven to be
      effective in approximately 50% of relapsed responders to IFN alpha monotherapy.
      In clinical practice, the decision to treat should be individualized and tailored
      on the basis of several virus- and host-related factors, particularly the grade
      and stage of liver disease, HCV genotype and levels of viremia. Appropriate
      monitoring of therapy by careful clinical evaluation, liver biochemistry and
      serum HCV RNA testing is mandatory. IFN alpha therapy may also prove to be
      effective in reducing the rate of HCC development in CHC regardless of whether a
      virological response is achieved, but this remains to be established.

PMID- 10938506
TI  - Hepatitis C infection: its sequelae and outcomes--State-of-the-Art Workshop,
      September 24 to 25, 1998. Canadian Association for the Study of the Liver.
AB  - This report summarizes a state-of-the-art workshop held in September 1998 on the
      "Natural History and Outcome of Hepatitis C Infection". Sixteen Canadian and two
      internationally renowned hepatologists were invited. A practical classification
      of HCV infection served as a framework for the meeting. The concepts of modelling
      of chronic disease, the epidemiology of HCV infection before the introduction of
      anti-HCV testing, and the outcome of various forms of chronic hepatitis C in
      adults and children were presented. Lectures on the outcome of HCV cirrhosis,
      hepatocellular carcinoma, the role of liver transplantation, the influence of
      host factors on outcome, iron overload in chronic hepatitis C and possible
      modification of the natural history by antiviral therapy were followed by
      discussion and consensus statements pertaining to each presentation. "The
      European Experience in Assessing Chronic Hepatitis C" was presented by Prof G
      Dusheiko from the United Kingdom, and Prof Leonard Seeff from the National
      Institutes of Health (United States) presented "The Epidemiology and Outcome of
      Hepatitis C Infection in the United States and the World".

PMID- 10938507
TI  - Ineffectiveness of hepatitis B vaccination in cirrhotic patients waiting for
      liver transplantation.
AB  - Cirrhotic patients who undergo liver transplantation are at risk of acquiring de
      novo hepatitis B virus (HBV) infection at the time of transplantation. It is
      common practice to immunize these patients against HBV, but the efficacy of
      vaccination is uncertain. The response to vaccination with a recombinant HBV
      vaccine was examined in 49 patients with cirrhosis before liver transplantation.
      Patients received three doses (20 mg) of Engerix-B (SmithKline Beecham) at zero,
      one and two months before transplantation, and their response was measured on the
      day of liver transplantation (9.3+/-1.2 months after the initial dose of
      vaccine). Results were compared with those reported in healthy adults vaccinated
      according to the same schedule. Fourteen of 49 cirrhotic patients (28%) developed
      antibodies to hepatitis B surface antigen (anti-HBs) levels of more than 10 U/L
      after vaccination compared with 97% of healthy controls. Four patients (8%) had
      anti-HBs levels of more than 100 U/L compared with 83% in healthy individuals.
      Mean anti-HBs titre in the 14 responders was 62 U/L compared with 348 U/L in
      controls. No factor was identified that predicted response to vaccination. One of
      49 patients acquired de novo HBV infection at the time of liver transplantation.
      Current HBV vaccination of cirrhotic patients waiting for liver transplantation
      is ineffective, and new strategies need to be developed to increase the response
      rate.

PMID- 10938508
TI  - Patients with chronic hepatitis C--who should not be treated?
AB  - The decision to treat a patient with chronic hepatitis C (CHC) is based on what
      is known about the risk factors for developing liver cirrhosis or hepatocellular
      carcinoma, as well as on conditions that contraindicate therapy or impair therapy
      effectiveness. Several factors, including age, treatment side effects, disease
      severity, concurrent diseases and life conditions, may render treatment decisions
      more difficult. This review focuses on identifying CHC patients who should not
      receive treatment.

PMID- 10938509
TI  - Hepatitis C.
AB  - Hepatitis C has been identified as the most common cause of post-transfusion
      hepatitis worldwide, accounting for approximately 90% of this disease in Japan,
      the United States and Western Europe. Hepatitis C is a major global public health
      problem. New infections continue to occur, and the source of infection includes
      transfusion of blood or blood products from unscreened donors; transfusion of
      blood products that have not undergone viral inactivation; parenteral exposure to
      blood through use of contaminated and inadequately sterilized instruments and
      needles used in medical, dental and 'traditional' medicine; procedures such as
      hemodialysis; high risk sexual practices; household or sexual contacts of
      hepatitis C virus (HCV)-infected persons; and infants of HCV-infected mothers. In
      many countries, the relative contribution of the various sources of infection has
      not been defined with population-based epidemiological studies. Such studies are
      necessary to enable countries to prioritize their preventive measures and to make
      the most appropriate use of available resources. Given the substantial morbidity
      and mortality attributable to HCV-related chronic liver disease, each country,
      irrespective of economic status, should develop a plan of HCV-related public
      health activities for the prevention of new HCV infections and the treatment of
      established chronic infections.

PMID- 10938510
TI  - Long term follow-up of patients with chronic hepatitis C treated with interferon
      alpha.
AB  - Interferon alpha (IFN alpha) treatment for chronic hepatitis C induces a
      sustained biochemical and virological response at six months after completing 24
      weeks of therapy in approximately 10% of patients. The long term durability of
      this 'sustained' response is still controversial. The aim of this multicentre
      study was to assess the long term virological response in patients considered to
      have achieved a sustained biochemical response six months after completing IFN
      treatment. The majority (36 of 41) of the sustained responders identified had
      been treated for six months with IFN therapy. Twenty-nine of the 41 patients
      (70%) had undetectable hepatitis C virus (HCV) RNA after a mean follow-up of 38
      months after cessation of treatment (range six to 92 months). All but one of
      those 29 individuals had normal serum alanine aminotransferase (ALT) levels. Of
      the 16 patients (out of 41) who had been tested for HCV RNA six months after
      treatment, HCV RNA remained undetectable in 14 (88%) at final follow-up. Serum
      ALT values in the 11 of 12 patients whose HCV RNA was positive at final follow-up
      were lower than pretreatment values, and in six cases were within the normal
      range. The long term sustained virological response in those considered a
      'sustained responder' six months after receiving only six months of IFN is high.
      Measurement of ALT is an unreliable marker of sustained response to therapy.

PMID- 10938511
TI  - Fasciitis complicating subcutaneous injection of interferon beta.
AB  - Data pertaining to 65 patients treated at the Health Sciences Center Hepatology
      Research Unit in Winnipeg, Manitoba describing local complications related to
      subcutaneous interferon (IFN) injection administered to treat hepatitis C virus
      infection are presented. Nine patients experienced local erythematous reactions
      at the injection region. No life-threatening complications were identified. One
      case of fasciitis complicating IFN beta injection - a complication not previously
      reported - was successfully managed with surgical debridement and antibiotic
      therapy. This case is a dramatic example of why sterile technique during
      infections must be adhered to.

PMID- 10938512
TI  - Diagnosis and management of chronic hepatitis C.
AB  - This mini-review is devoted to the main questions of diagnosis, treatment and
      prevention of chronic hepatitis C (CHC). Diagnosis of CHC is based on
      virological, biochemical and histological findings. The etiology of CHC should be
      proven by the presence of antibody to hepatitis C virus (anti-HCV) and detection
      of viral nucleic acid (HCV RNA), using qualitative and quantitative polymerase
      chain reaction or branched chain DNA techniques. Serum aminotransferase levels
      can reflect the biochemical activity of liver disease, while biopsy is very
      important in the grading and staging of the pathological process. The generally
      accepted treatment of CHC is interferon (IFN); however, recently, the combination
      of IFN with the oral nucleoside analogue ribavirin has become the therapy of
      choice, not only for relapsers but also for naive patients. Prevention of
      hepatitis C by vaccination is not yet available. Screening blood donors and
      members of high risk groups, as well as ensuring good public health measures, are
      imperative to inhibit the spread of HCV.

PMID- 10938513
TI  - [Pathogenesis and treatment of hypersensitivity pneumonitis].
AB  - Hypersensitivity pneumonitis (HP) is a granulomatous interstitial lung disease
      resulting from an immunologic reaction to the repeated inhalation of organic
      dusts and active chemicals. There are 50 or more groups of HP, but the prevalence
      varies from country to country, and even within a country, depending on a variety
      of occupational or environmental inhalants. In Western coutries farmer's lung,
      bird fancier's disease, humidifier lung, and air-conditioner disease are common,
      but in Japan summer-type HP is the most prevalent group. Summer-type HP is a
      house-related illnes induced by Trichosporon asahii and Trichosporon mucoides
      which contaminate the patients' home environments in hot and humid conditions.
      The polysaccharide antigen contains mannan backbone attached with short side
      chains consi-sting of mannose, xylose, and glucuronic acid residues. Both immune
      complex-mediated and T cell-mediated immune responses to the yeast are involved
      in the induction and development of the disease. Host factors such as HLA-DQw3
      and cigarette smoking also play an important role in the develop-ment or
      suppression of the disease. An assay for serum anti-Trichosporon antibody by a
      Triko Kit is very useful for the serodiagnosis, and sanitization by cleaning,
      disinfecting, and removing from the colonizing location of Trichosporon prevents
      recurrence of the disease. Summer-type HP induced by Trichosporon is a new type
      of HP. It can be found in other countries including most Western countries,
      because Trichosporon asahii and Trichosporon mucoides distribute in the temperate
      and subtropical areas of the world.

PMID- 10938514
TI  - [Molecular mechanisms underlying cell adhesion--molecules mediating lymphocyte
      migration].
AB  - Adhesion molecules play crucial roles in a variety of in vivo responses such as
      development of various tissues in embryos and also in the body defence mechanism
      in the postnatal period. Defects in adhesion molecules thus result in various
      pathological disorders. Recent investigation has identified a large number of
      novel adhesion molecules, particularly those involved in the extravasation of
      leukocytes including lymphocytes. However, there still appears to be a
      substantial number of unidentified adhesion molecules. In addition, signal
      transduction as well as regulatory mechanisms of adhesion molecules remain not
      fully explored. I will herein describe general characteristics of adhesion
      molecules and also discuss issues that need to be urgently resolved in the field
      of cell adhesion.

PMID- 10938515
TI  - [The role of fungal allergy in bronchial asthma].
AB  - Fungus is known to be one of the causative allergens inducing bronchial asthma as
      are housedustmites, pollen and pet dander. Outdoor airborne fungi such as
      Cladosporium, Alternaria, Penicillium and Aspergillus are important inducing IgE
      antibody formation. In addition to these common fungi, the indoor fungi
      Aspergillus restrictus, Neurospora and Eurotium are important allergenic fungi
      which have recently been identified. The yeast Candida albicans, is a common
      commensal of the human oral and vaginal mucosae and gastrointestinal tract and
      part of the normal flora, is known as one of the main allergens causing bronchial
      asthma. We examined the allergenicity of mannan (Mn) as a cell-wall constituent
      and acid protease (CAAP) as a secreted enzyme of C. albicans. We previously
      reported cases of atopic asthma caused by CAAP and stressed the role of CAAP as
      an important allergen in mucosal allergy to C. albicans 9). The levels of the
      antibodies to these antigens in the sera of asthmatic patients who showed
      positive immediate intradermal response to crude C. albicans (n=86) were
      measured. Anti-Mn IgE and IgG antibody levels were measured by liquid-phase assay
      (AlaSTAT). Anti-CAAP and anti-crude C. albicans IgE and IgG antibody levels were
      measured by RAST and AlaSTAT. Anti-Mn A and anti-Mn B IgE antibody titers were
      strongly correlated (r=0.87), while anti-Mn A and anti-CAAP IgE titers were not
      correlated. However, all of the anti-Mn A IgE positive sera and all of the anti
      CAAP IgE positive sera were positive for IgE to crude-C. albicans. This indicates
      that both Mn and CAAP are C. albicans-related allergens. Titers of IgG antibodies
      to Mn A and crude C. albicans were highly correlated (r=0. 90). Results of
      inhibition assays performed using other fungal antigens as inhibitors showed that
      Mn is a cross reactive allergen among different fungi and that CAAP is a C.
      albicans specific allergen causing human mucosal allergic reaction.

PMID- 10938516
TI  - [Learning from fungus allergy in atopic dermatitis patients].
AB  - It has been recognized that there are considerable variations in their skin
      reactivity to environmental allergens as well as in immunoreactivities, even in
      AD patients with similar signs and symptoms. Some AD patients have high serum IgE
      antibody levels, while others show low levels. There are also differences in the
      kinds of triggering factors that are related to the development and maintenance
      of AD, e.g., allergic or non-allergic. Even among AD patients with high titers of
      serum IgE antibodies, the kinds and number of allergens involved in the
      exacerbation of AD are different and can change with time. The types of the
      underlying allergic reactions vary as well, i.e., some show immediate reactions,
      while others show delayed type hypersensitivity responses to environmental
      allergens. Thus, even AD patients diagnosed by the established criteria may have
      remarkably different backgrounds. When we looked over our published data, we
      noticed that there were differences in levels of IgE RAST and skin reactions
      between AD with atopic respiratory diseases (ARD) and pure AD without ARD. Levels
      of IgE RAST against airborne allergens, which come into the body mainly through
      the respiratory tract, were higher in AD with ARD, while those against allergens
      such as Candida albicans and Malassezia furfur, which can colonize on the skin,
      were higher in pure AD. In addition to these Th2-mediated immunological
      abnormalities, Th1-mediated DTH reaction and lymphocyte proliferation indices
      against airborne allergens were remarkably low in AD with ARD, whereas those
      against Candida albicans and Malassezia furfur were relatively preserved,
      although they were lower than those found in normal subjects. We understand from
      these findings that routes of allergen entry are important for the outcome of the
      resultant allergic reactions. This point of view is important answering questions
      such as how AD develops and how it can be prevented from the insults of each
      allergen.

PMID- 10938517
TI  - Cells of different ploidy are often present together in Cryptococcus neoformans
      strains.
AB  - We examined the ploidy of C. neoformans strains using both laser scanning
      cytometry and a fluorescence microscope equipped with a photomultiplier. Haploid
      strains consisted of normal-sized cells with a haploid DNA amount. In the cell
      population there were also large-sized cells with a diploid DNA amount. These
      large cells in haploid strains were isolated using a Skerman micromanipulator,
      cultivated, and were able to generate diploid clones. Even after only 3-5
      transfers on slants, haploid cells were present in all the diploid clones
      examined. Conversely, haploid clones obtained by single-cell-isolation of normal
      sized cells from haploid strains were also shown to contain diploid cells after 3
      5 transfers. Fresh haploid isolates from the environment similarly contained
      diploid cells after 3-5 transfers. Thus, a cellular ploidy shift was shown to
      occur widely in C. neoformans strains.

PMID- 10938518
TI  - Study on the influence of pretreatment temperature for plasma (1-->3)-beta-D
      glucan measurement using kinetic turbidimetric Limulus assay and clinical
      evaluation of (1-->3)-beta-D-glucan measurement methods.
AB  - We clinically evaluated three commercially available (1-3)-beta-D-glucan
      measurement methods for the diagnosis of fungal infections: the kinetic
      turbidimetric, the end-point chromogenic, and the kinetic chromogenic Limulus
      tests. For the kinetic turbidimetric assay, we examined a dilution and heating
      pretreatment method at 70 degrees C for plasma to eradicate irregular (1-3)-beta
      D-glucan values caused by changes in the nonspecific turbidity of the reaction
      mixture, a problem occasionally encountered when the ordinary method is used
      (pretreated at 80 degrees C). With the 70 degrees C-pretreatment method, the
      nonspecific turbidity was eradicated and the values of (1-3)-beta-D-glucan were
      lower than those obtained by the ordinary method. Thus, the 70 degrees C
      pretreatment method was less sensitive than the ordinary method, but its
      specificity was higher. The overall agreement rates between the kinetic
      turbidimetric assay and chromogenic assay were near 90%. Some samples in the
      control group showed unexpectedly high (1-3)-beta-D-glucan values with the
      kinetic chromogenic assay. The measurement with the end-point chromogenic assay
      was influenced by sulfa drugs. In the kinetic turbidimetric method, the 70C
      pretreatment method is more effective than the ordinary method.

PMID- 10938519
TI  - Isolation of Candida dubliniensis from the oral cavity of an HIV-positive child
      in Brazil.
AB  - Candida dubliniensis is a newly-recognized Candida species and an important
      infectious pathogen, particularly for HIV-positive patients. >From oral smear
      samples from the radix linguae of 173 HIV-positive children, we obtained four
      yeast isolates which took a blue-green color on CHROMagar Candida plate at 37
      degrees C for 48 hours from one HIV-positive 3-year-old boy in Brazil. The
      isolates were difficult to grow on potato dextrose agar plate at 42 degrees C,
      produced abundant chlamydospores on a cornmeal agar plate with Tween 80, and
      sprouted germ tubes in saline with horse serum, and the antigenic profile by
      CANDIDA CHECK test was useless. Carbohydrate assimilation tests by ID32C showed
      no reference code number in the reference book. The isolates were subjected to
      molecular biological assay of the DNA sequence of the large-subunit ribosomal DNA
      region (D1/D2) and randomly amplified polymorphic DNA (RAPD). The DNA sequence
      agreed with those of standard C. dubliniensis strains, and therefore, the
      isolates were identified as C. dubliniensis. RAPD band pattern analysis indicated
      that the clinical isolates might summarize one genotype. Although the child did
      not present oral lesions, the fungus might be latent for opportunistic infection.

PMID- 10938521
TI  - [1996 epidemiological survey of dermatophytoses in Japan. Epidemiological
      Investigation Committee for Human Mycoses in the Japanese Society for Medical
      Mycology].
AB  - An epidemiological investigation on dermatophytoses in Japan for the year 1996
      was carried out with the following results. The number of dermatomycoses patients
      visiting the fifteen cooperating institutes that year was 8,402. New outpatients
      with this condition accounted for 13.1% of all new outpatients in these
      institutes. Dermatophytoses patients numbered 7,395 and were composed of: tinea
      pedis 4,764 (64.4%), tinea unguium 1,487 (20.1%), tinea corporis 558 (7.5%),
      tinea cruris 369 (5.0%), tinea manuum 195 (2.6%), tinea capitis 11, kerion Celsi
      7, tinea barbae 1 and other forms 3. Of these, 113 were children under 15 years
      of age. Species and incidences of the 2,615 strains isolated from the patients
      with dermatophytoses were as follows: Trichophyton (T.) rubrum 1,828 (69. 9%), T.
      mentagrophytes 743 (28.4%) Epidermophyton floccosum 20 (0. 8%), Microsporum (M.)
      canis 13 (0.5%), M. gypseum 5, T. violaceum 2, and 4 undetermined strains.
      Candidiasis was found in 722 individuals: intertrigo 299, erosio interdigitalis
      95, erythema infantum 89, oral candidiasis 63, paronychia et onychia 56, genital
      candidiasis 56, onychomycosis 24, chronic mucocutaneous candidiasis 1 and other
      atypical forms of candidiasis 39. Patients with tinea versicolor numbered 265 and
      those with Malassezia folliculitis 15. There were five cases of deep dermal
      mycoses: three of sporotrichosis, one of chromomycosis and one of aspergillosis.
      The results of superficial dermatophytoses for the year 1996 differed from those
      of 1991-92 in the following points: Tinea corporis and tinea cruris were lower in
      number, while tinea unguium had increased in ratio and number. M. canis infection
      tended to decrease gradually. In the age-distribution of tinea, in every clinical
      form the peak of distribution curve shifted to a more elderly age group.

PMID- 10938520
TI  - [Preventive effects of various socks against adhesion of dermatophytes to healthy
      feet].
AB  - We studied the preventive effects of socks against dermatophyte infection.
      Wearing various socks (cotton socks, nylon stockings, wool socks and "tabi"), a
      healthy volunteer walked on a bath mat on which a patient with tinea pedis had
      stepped earlier. The volunteer pressed her right foot with socks onto large agar
      medium (Foot-press method), then, took off the socks and performed the Foot-press
      method again. The number of colonies of isolated dermatophytes on the medium was
      counted. The number of isolated colonies from the sole after taking off the nylon
      stockings was larger than that from the foot wearing the stockings. Dermatophytes
      were also isolated from the sole after taking off cotton socks. In contrast, few
      dermatophytes were isolated from the sole after taking off wool socks or "tabi".
      On microscopic observation, fibers of the nylon stockings and cotton socks were
      seen to be loose enough for dermatophytes to pass through. In contrast with those
      socks, fibers of wool socks and "tabi" were tight or fluffy. In conclusion, the
      nylon stockings and cotton socks are unsatisfactory in preventing the adhesion of
      dermatophytes.

PMID- 10938522
TI  - [Dermatophytosis of the external auditory meatus].
AB  - Dermatophytosis of the external auditory meatus is believed to be a fairly rare
      disease. In the past three and a half years we have had seven cases of
      dermatophytosis in the external auditory meatus. All cases except one were
      associated with tinea of other lesions. Case 1: A 44-year-old man had tinea of
      the auricle, tinea pedis and tinea unguium. Case 2: A 14-year-old boy, the son of
      case 1 had no tinea elsewhere on his body, including the auricle. He scratched
      the auditory meatus with an earpick which his father had used. Case 3: A 62-year
      old man had tinea of the auricle, tinea pedis and tinea unguium. Case 4: A 50
      year-old man had tinea of the auricle, tinea pedis and tinea unguium. Case 5: A
      36-year-old man had tinea of the auricle, tinea pedis, tinea unguium and tinea
      cruris. Case 6: A 30-year-old woman had tinea of the auricle. Case 7: A 68-year
      old man had tinea of the auricle, tinea pedis, tinea unguium and tinea manuum.
      Endoscopic examination (except for cases 4 and 7) revealed dry cerumen from
      cartilaginous to bony region of the external auditory meatus. Direct examination
      using KOH method of the cerumen in all cases demonstrated numerous fungal
      elements. Fungal cultures identified Trichophyton rubrum except for cases 3 and
      6. All cases were successfully treated with oral itraconazole or terbinafine. We
      suggest that tinea of the external auditory meatus is frequently associated with
      that of the auricle.

PMID- 10938523
TI  - Targeted delivery of prostaglandin E1 to hepatocytes using galactosylated
      liposomes.
AB  - Prostaglandin E(1) (PGE(1) ) was incorporated in galactosylated liposomes
      containing cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiogalactosyle thyl)amino)b
      utyl)formamide (Gal-C4-Chol) intended for hepatocyte-selective delivery.
      Liposomes composed of distearoylphosphatidylcholine (DSPC)/cholesterol (Chol)/Gal
      C4-Chol (60&ratio;35&ratio;5) were prepared and compared with DSPC/Chol
      (60&ratio;40) liposomes. After intravenous injection of [(3) H]-labeled PGE(1) or
      cholesteryl hexadecyl ether (CHE) with the liposomal formulation, mice were
      sacrificed at a series of times, and the radioactivity in tissues was determined.
      Up to about 80% of [(3) H]CHE in galactosylated liposomes had accumulated in the
      liver 10 min after intravenous injection and the liver accumulation of the
      incorporated [(3) H]PGE(1) was significantly higher than that in control
      liposomes during the entire test period. The pharmacological activity was
      examined in mice with fulminant hepatitis induced by peritoneal injection of
      carbon tetrachloride. Intravenous injection of PGE(1) incorporated in
      DSPC/Chol/Gal-C4-Chol (60&ratio;35&ratio;5) liposomes significantly suppressed
      the GPT increase, whereas PGE(1) (dissolved in saline) and PGE(1) incorporated in
      DSPC/Chol (60&ratio;40) liposomes had little effect.

PMID- 10938524
TI  - Cellular uptake of PEO surface-modified nanoparticles: evaluation of
      nanoparticles made of PLA:PEO diblock and triblock copolymers.
AB  - Nanoparticles with either physically adsorbed or covalently bound poly(ethylene
      oxide) (PEO) coatings were produced from various combinations of poly(lactic
      acid) (PLA) and diblock or triblock copolymers of PLA and PEO. The particles were
      produced by the salting-out process and purified by the cross-flow filtration
      technique. The amount of PEO at the nanoparticle surface, as well as the residual
      amount of emulsifier poly(vinyl alcohol) were assessed, with a good correlation
      with expected values. Stability of the nanoparticulate suspensions was studied at
      4 degrees C and after freezing under various conditions for up to 6 months. The
      nanoparticle redispersibility after storage was related to the thermal behavior
      of the PEO coatings. The in vitro cellular uptake of the different types of
      nanoparticles was compared by flow cytometry after incubation with human
      monocytes in serum and in plasma. The influence of the PEO molecular weight and
      surface density on the particle uptake was especially marked for the diblock and
      triblock copolymer formulations, with a decrease in uptake of up to 65% with one
      of the diblock copolymer formulations. Nanoparticles made of triblock copolymer
      with short PEO chains at their surface in the postulated "loop conformation"
      proved to be as resistant to cellular uptake as nanoparticles made of diblock
      copolymers with PEO chains in the "brush conformation".

PMID- 10938525
TI  - Low density lipoprotein as a carrier of cytostatics in cancer chemotherapy: study
      of stability of drug-carrier complexes in blood.
AB  - Several solid tumour and leukemia cell types have a higher low density
      lipoprotein (LDL) uptake than the corresponding normal cells. We are
      investigating the possibilities to use LDL as a drug carrier to increase the
      selectivity of antineoplastic drugs in cancer chemotherapy. We have developed a
      method to incorporate lipophilic cytotoxic agents without interfering with the in
      vitro and in vivo properties of LDL. In this study, we examined the stability of
      some drug-LDL complexes in blood and plasma as this is an important prerequisite
      to achieve a selective therapy. The in vitro dialysis of N-trifluoroacetyl
      adriamycin-14-valerat-LDL (AD-32-LDL) against plasma revealed a slow dissociation
      of the complex. The same method showed a fast and total leakage of paclitaxel
      from paclitaxel-LDL into the plasma chamber. The dissociation of paclitaxel was
      confirmed by an autoradiographic study of the distribution of paclitaxel-LDL in
      tumour-bearing mice. In patients with leukemia the rapid plasma dissociation of
      AD-32 from LDL illustrated a much higher in vivo instability of this complex.
      With this method, cholesteryl-linoleate only could be incorporated into LDL in a
      stable manner as shown by dialysis and autoradiography results. The incorporation
      of cytotoxic drug derivatives, containing lipophilic anchors, is now under study
      in order to obtain LDL complexes with better plasma stability.

PMID- 10938526
TI  - Reduction of the uptake by a macrophagic cell line of nanoparticles bearing
      heparin or dextran covalently bound to poly(methyl methacrylate).
AB  - Amphiphilic and fluorescent covalently labelled core-shell nanoparticles based on
      poly(methyl methacrylate) (PMMA), were prepared by random copolymerisation of N
      Vinyl carbazole (NVC) with MMA, initiated on polysaccharidic radicals, yielding
      diblock copolymers of either dextran-P(MMA-NVC) (Nanodex* particles), or heparin
      P(MMA-NVC) (Nanohep* particles). Nanoparticles made from random copolymers of
      P(MMA-NVC) (PMMA*) were used as controls. The interactions between particles and
      a J774A1 murine macrophage-like cell line were quantified by direct measurement
      of the cell-associated fluorescence. The association with the cells occurred
      within 30 min. Nanodex* and Nanohep* showed considerably less association than
      the control PMMA* particles. Some of the particle uptake could be attributed to
      phagocytosis, but more than 50% of the cell-associated fluorescence persisted at
      low temperature or in the presence of cytochalasin B. The results suggest that
      both the adsorption and the internalisation processes can be inhibited by the
      presence of the polysaccharide chains. In conclusion, these results confirm that
      nanoparticles prepared with heparin or dextran chains on their surface, probably
      in a brush-like configuration, show "stealth" properties in vitro as had
      previously been observed in vivo. If this biomimetic approach can also be applied
      to biodegradable polymers, these systems would provide at least an alternative to
      PEG-modified particles as long-circulating drug carriers systems or imaging
      agents.

PMID- 10938527
TI  - Lectin-mediated bioadhesion: preparation, stability and caco-2 binding of wheat
      germ agglutinin-functionalized Poly(D,L-lactic-co-glycolic acid)-microspheres.
AB  - To take advantage of the cytoadhesive characteristics of Wheat germ agglutinin
      (WGA) for improved particulate drug delivery, the interaction between WGA-grafted
      poly(D,L-lactic-co-glycolic acid)-microspheres and Caco-2 monolayers was
      investigated using bovine serum albumin (BSA) or glycine coated microspheres as a
      control. Covalent immobilization of WGA by the carbodiimide/N-hydroxysuccinimide
      method on 4 microm microspheres yielded a surface density of 9.67+/-1.21x10(6)
      molecules/particle, whereas 0.22+/-0.04x10(6) WGA-molecules were bound by
      physical adsorption. After storage for 21 days in HEPES-buffer and treatment of
      the particles with 5 M urea, 86% of covalently linked lectin was still attached
      to the particles. At 4 degrees C the Caco-2 binding rate of both, WGA- and BSA
      modified particles increased with addition of increasing numbers of particles
      until saturation was reached at 38150+/-1740 (WGA) or 12066+/-1195 (BSA)
      microspheres bound/mm(2) Caco-2 monolayer. Inhibition of Caco-2 binding of WGA
      functionalized microspheres by chitotriose indicated for specificity of the
      interaction. As observed by confocal laser scanning microscopy, the fluorescein
      loading of the particles was accumulated intracellularly after incubation of Caco
      2 monolayers with WGA-modified microspheres contrary to glycine-grafted
      microspheres. Additionally, in case of WGA-functionalized microspheres the amount
      of cell associated fluorescein was 200-fold higher than that of the free
      solution. In conclusion, WGA-modified microspheres are expected to enhance
      intestinal transport of incorporated drugs due to cytoadhesion provided by the
      lectin coating.

PMID- 10938529
TI  - Enhancement of transport of D-melphalan analogue by conjugation with L-glutamate
      across bovine brain microvessel endothelial cell monolayers.
AB  - In this paper, the L-glutamate (L-Glu) transport system was targeted to improve
      the delivery of a model compound, p-di(hydroxyethyl)-amino-D-phenylalanine (D
      MOD), through the blood-brain barrier (BBB) in vitro cell culture model. D-MOD is
      an analogue of an antitumor agent D-melphalan. To target the L-Glu transport
      system, D-MOD was conjugated to L-Glu to give D-MOD-L-Glu conjugate. D-MOD and D
      MOD-L-Glu transport properties were evaluated using the bovine brain microvessel
      endothelial cell (BBMEC) monolayers. The results suggest that D-MOD-L-Glu
      conjugate permeates through the BBMEC monolayers more readily than the parent D
      MOD. The improvement of transport may be due to the recognition of D-MOD-L-Glu by
      the L-Glu transport system. The transport mechanism was evaluated using several
      different experiments including: (a) concentration-dependent studies; (b)
      temperature-dependent studies; (c) substrate inhibition studies; and (d)
      metabolic inhibitor studies. The D-MOD-L-Glu transport was inhibited by the
      change of temperature from 37 degrees C to 4 degrees C. At higher concentrations,
      the transport of D-MOD-L-Glu reached plateau due to saturation. Furthermore, some
      amino acids (i.e., L-Glu, L-Asp, D-Asp, and L-Gln) inhibited the transport of D
      MOD-L-Glu; presumably the conjugate was competing with these amino acids for the
      same transport system. Metabolic inhibitors (i.e., 2,4-dinitrophenol and sodium
      azide) suppressed the transport of the conjugate. However, the conjugate was not
      transported by monocarboxylic acid, dipeptide and neutral amino acid
      transporters. In conclusion, the L-Glu transport system can be utilized to
      facilitate a non-permeable drug across the BBB by conjugating the drug with L-Glu
      amino acid.

PMID- 10938528
TI  - Absorption enhancement of a protein drug by nitric oxide donor: effect on nasal
      absorption of human granulocyte colony-stimulating factor.
AB  - The objective of this study was to evaluate the effect of a nitric oxide (NO)
      donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the nasal absorption of
      recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits and
      to evaluate the irritation (cytotoxicity) potential of the NO donor on the
      mucosal membrane using a cultured cell system (strain KB, human epidermoid
      carcinoma of the floor of the mouth). Significantly higher serum G-CSF
      concentration and increased total leukocyte count in the peripheral blood were
      observed after coadministration of rhG-CSF (100 microg/kg) with SNAP at various
      doses (0.3-3.3 mg/kg). The serum G-CSF concentration and the increased total
      leukocyte count were markedly decreased by the presence of the NO scavenger, 2-(4
      carboxyphenyl)-4,4,5,5-tetramethyl-imidazole-1-oxyl 3-oxide sodium salt (carboxy
      PTIO), in combination with rhG-CSF and SNAP. However, no significant inhibitory
      effect of glutathione (peroxynitrite scavenger) on the absorption-enhancing
      effect of SNAP was observed. These results suggest that carboxy-PTIO inhibits the
      absorption-enhancing effect of NO released from SNAP. We found that SNAP has a
      very low potential for cytotoxicity, as evaluated by the cell detachment assay,
      release of lactate dehydrogenase (LDH) from cultured cells and morphological
      observations of nasal tissue of rabbits. It is concluded that a NO donor such as
      SNAP is a promising absorption enhancer for nasal protein-drug delivery.

PMID- 10938530
TI  - A Kinetic Study on the Interaction between Tazobactam (A Penicillanic Acid
      Sulphone Derivative) and Active-Site Serine beta-Lactamases.
AB  - The interaction between tazobactam and several chromosome- and plasmid-encoded
      (TEM, SHV, PSE types) class A and C beta-lactamases was studied by
      spectrophotometry. Tazobactam behaved as a competitive inhibitor or inactivator
      able to restore in several cases the efficiency of piperacillin as a partner beta
      lactam. A detailed kinetic analysis permitted measurement of the acylation
      efficiency for some cephalosporinases and broad-spectrum beta-lactamases; the
      presence of a turn-over of acyl-enzyme complex was also evaluated.

PMID- 10938531
TI  - Selective Inhibition of Monoamine Oxidase B by Aminoethyl Substituted Benzyl
      Ethers.
AB  - Aminoethyl 3-chlorobenzyl ether was shown previously (Ding, C.Z. and Silverman,
      R.B. (1993). Bioorg. Med. Chem. Lett., 3, 2077-2078) to be a potent and selective
      time-dependent, but reversible inhibitor of monoamine oxidase B (MAO B). Based on
      this result, a series of novel aminoethyl substituted benzyl ethers was
      synthesized and the compounds were examined as potential inhibitors of both
      isozymic forms of MAO. Each compound in the series inhibits both MAO A and MAO B
      competitively, and IC(50) values for each compound were determined. In general,
      the B isozyme is much more sensitive to these inhibitors than the A isozyme
      (except for the o- and p-substituted nitro analogues), in some cases by more than
      two orders of magnitude. The selectivity in favor of MAO B inhibition is
      relatively high for all of the meta-substituted analogues and quite low for all
      of the ortho-substituted analogues. Having the substituent at the ortho-position
      is most favorable for MAO A inhibition. With MAO B the meta-analogues were, in
      general, more potent than the corresponding ortho- and para-analogues with
      respect to their reversible binding constants. The meta-iodo analogue is the most
      potent analogue.

PMID- 10938532
TI  - Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular
      Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4
      Thia- diazole-2-Sulfonamide.
AB  - Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine
      with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and
      deprotection of the phthalimido group the corresponding 5-(omega
      aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta
      aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or
      acyl halides afforded a series of compounds possessing beta
      alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of
      the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors
      of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV
      (membrane-bound form), but especially against CA II and CA IV (in nanomolar
      range), the two isozymes known to play an important role in aqueous humor
      secretion within the ciliary processes of the eye. Some of the synthesized
      inhibitors possessed good water solubility (as hydrochlorides or sodium salts)
      and were applied as 2% solutions directly into the eye of normotensive or
      glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was
      observed for many of them for prolonged periods of 1-2 h, and the active drug was
      detected in eye tissues and fluids indicating that the antiglaucoma effect is due
      to CA inhibition within the eye.

PMID- 10938533
TI  - Inhibition of Glutathione Reductase by Isoproterenol Oxidation Products.
AB  - Oxidative stress induced by catecholamines is a well recognized toxic event. This
      effect has been extensively observed in the heart, where high levels of
      catecholamines cause enzyme inhibition, lipid peroxidation, energy depletion and
      myocardial necrosis. Catecholamines can be converted into o-quinones and undergo
      cyclization into aminochromes. This process can occur enzymatically or through
      autoxidation and involves the formation of free radicals. Aminochromes are highly
      reactive molecules that can cause oxidation of protein sulfhydryl groups and
      deamination catalysis, among other deleterious effects; in addition, inhibition
      of some enzymes has been also reported. We have studied the effects of
      isoproterenol oxidation products (IOP) on glutathione reductase (GR) activity in
      vitro. Isoproterenol (ISO) autoxidation was conducted at 37 degrees C in the
      dark, for 4 h at pH 7.0 and this process was monitored by UV spectrophotometry at
      both 340 and 490 nm. Addition of the autoxidized solution to GR in the presence
      of oxidized glutathione (GSSG) and NADPH showed that IOP inhibits GR in a
      competitive mode and that this effect increases during the 4 h incubation period.
      This inhibitory effect of IOP was partially prevented by the addition of reduced
      glutathione (GSH), L-cysteine and ascorbic acid to the reaction mixtures.

PMID- 10938534
TI  - Synthesis and Mechanism of Action of Novel Thiocarbamate Inhibitors of Human
      Leukocyte Elastase.
AB  - Several peptidyl thiocarbamate inhibitors of human leukocyte elastase were
      synthesized in the molecular weight range of 700-800. Two different sequences
      with lysine at the P(3) and ornithine at the P(4) positions were synthesized.
      Most of the inhibitors with large molecular weights showed high inhibitory
      capacity with Ki values as low as 10(-8) M. Compounds immobilized on
      poly,alpha,beta-[N-(2-hydroxyethyl)-d,l-aspartamide] (PHEA) polymers with an
      average molecular weight of 36,000 showed higher inhibitory capacity than their
      free forms.

PMID- 10938535
TI  - Non-Enzymatic Glycosylation (or Glycation) and Inhibition of the Pig Heart
      Cytosolic Aspartate Aminotransferase by Glyceraldehyde 3-Phosphate.
AB  - Glyceraldehyde 3-phosphate (Glyc3P), a glycolytic intermediate, non-enzymatically
      glycosylated (or glycated) and inhibited the pig heart cytoplasmic aspartate
      aminotransferase (cAAT). Glyc3P (5.0 mM) decreased cAAT activity by 47% after 1
      min at 23 degrees C. cAAT activity remained unchanged after a 24 h incubation
      with either glucose 6-phosphate (5.0 mM) or ribose 5-phosphate (5.0 mM).
      Increasing the incubation pH from 6.4 to 7.8 or the incubation temperature from
      23 degrees C to 50 degrees C enhanced Glyc3P's inhibitory effect on cAAT
      activity. Glyc3P (250-500 uM) decreased the thermal stability of cAAT as
      evidenced by lowering the T(m) or temperature that caused a 50% irreversible loss
      of cAAT activity (69 degrees C, control; 58.5 degrees C, 500 uM Glyc3P). Glyc3P
      decreased cAAT amino group content and increased glycation products, which were
      measured by adduct formation, fluorescence and protein crosslinking.

PMID- 10938536
TI  - Interaction of Pig Kidney and Lentil Seedling Copper-Containing Amine Oxidases
      with Guanidinium Compounds.
AB  - The effect of guanidinium compounds on the catalytic mechanism of pig kidney and
      lentil seedling amine oxidases has been investigated by polarographic techniques
      and spectroscopy. Guanidine does not inhibit the lentil enzyme and is a weak
      inhibitor for pig kidney amine oxidase (K(i) =1 mM), whereas aminoguanidine is an
      irreversible inhibitor of both enzymes, with a K(i) value of 10(-6) M. 1,4
      Diguanidino butane (arcaine) is a competitive inhibitor for both pig and lentil
      amine oxidases. Amiloride is a competitive inhibitor for pig enzyme, but upon
      prolonged incubation with this drug the enzyme gradually loses its activity in an
      irreversible manner.

PMID- 10938537
TI  - Fluorescence monitoring of the conformational change in alpha 2-macroglobulin
      induced by trypsin under second-order conditions: the macroglobulin acts both as
      a substrate and a competitive inhibitor of the protease.
AB  - The reaction of bovine pancreatic trypsin with human plasma alpha(2)
      macroglobulin (alpha(2)M) was studied at 25 degrees C, using equimolar mixtures
      of E and I in 50 mM potassium phosphate buffer, pH 7. The conformational change
      in alpha(2)M was monitored through the increase in protein fluorescence at 320 nm
      (exc lambda, 280 nm). At [alpha(2)M](0) =[E](0) =11.5-200 nM, the fluorescence
      change data fit the integrated second-order rate equation, (F(infinity) -F(0)
      )/(F(infinity) -F(t) )=1+k(i,obsd) [alpha(2)M](0) t, indicating that cleavage of
      the bait region in alpha(2)M was the rate-determining step. The apparent rate
      constant (k(i,obsd)) was found to be inversely related to reactant concentration.
      The kinetic behavior of the system was compatible with a model involving
      reversible, nonbait region binding of E to alpha(2)M, competitively limiting the
      concentration of E available for bait region cleavage. The intrinsic value of
      k(i) was (1.7+/-0.24) x 10(7) M(-1) s(-1).K(p), the inhibitory constant
      associated with peripheral binding, was estimated to be in the submicromolar
      range. The results of the present study point to a potential problem in
      interpreting kinetic data relating to protease-induced structural changes in
      macromolecular substrates. If there is nonproductive binding, as in the case of
      trypsin and alpha(2)M, and the reactions are monitored under pseudo first-order
      conditions ([S](0) >>[E](0) ), an intrinsically second-order process (such as the
      rate-limiting bait region cleavage in alpha(2)M) may become kinetically
      indistinguishable from an intrinsically first-order process (e.g. rate-limiting
      conformational change). Hence an excess of one component over the other should be
      avoided in kinetic studies addressing such systems.

PMID- 10938538
TI  - Protease inhibitors: Synthesis of L-alanine hydroxamate sulfonylated derivatives
      as inhibitors of clostridium histolyticum collagenase.
AB  - L-alanine hydroxamate derivatives were obtained by reaction of alkyl/arylsulfonyl
      halides with L-alanine, followed by treatment with benzyl chloride, and
      conversion of the COOH moiety to the CONHOH group with hydroxylamine in the
      presence of carbodiimides. Other derivatives were obtained by reaction of N
      benzyl-alanine with aryl isocyanates, arylsulfonyl isocyanates or benzoyl
      isothiocyanate, followed by a similar conversion of the COOH to the CONHOH
      moiety. The obtained compounds were assayed as inhibitors of Clostridium
      histolyticum collagenase, ChC (EC 3.4.24.3), a zinc enzyme which degrades triple
      helical collagen. The hydroxamate derivatives were generally 100-500 times more
      active than the corresponding carboxylates. In the series of synthesized
      derivatives, substitution patterns leading to the most potent ChC inhibitors were
      those involving perfluoroalkylsulfonyl- and substituted-arylsulfonyl moieties,
      such as pentafluorophenylsulfonyl, 3- and 4-protected-aminophenylsulfonyl-, 3-
      and 4-carboxy-phenylsulfonyl-, 3-trifluoromethyl-phenylsulfonyl-, or 1- and 2
      naphthylsulfonyl among others. Similarly to the matrix metalloproteinase (MMP)
      hydroxamate inhibitors, ChC inhibitors of the type reported here must incorporate
      hydrophobic moieties at the P(2') and P(3') sites, in order to achieve tight
      binding to the enzyme.

PMID- 10938539
TI  - Inhibition of acidic sphingomyelinase by xanthone compounds isolated from
      Garcinia speciosa.
AB  - Sphingomyelinase is considered to be involved in the regulation of apoptosis and
      cell growth. In the course of our screening for acidic sphingomyelinase
      inhibitors we isolated three xanthone compounds, alpha-mangostin, cowanin, and
      cowanol, from the bark of Garcinia speciosa. These compounds competitively
      inhibited bovine brain-derived acidic sphingomyelinase with IC(50) values of
      14.1, 19.2, and 10.9 microM, respectively and inhibited the acidic
      sphingomyelinase more effectively than the neutral sphingomyelinase of bovine
      brain. alpha-Mangostin inhibited the acidic sphingomyelinase in the most
      selective manner. alpha-Mangostin was chemically modified and its structure
      activity relationships are discussed.

PMID- 10938540
TI  - Carbonic anhydrase activators: synthesis of high affinity isozymes I, II and IV
      activators, derivatives of 4-(4-tosylureido-amino acyl)ethyl-1H-imidazole
      (histamine derivatives).
AB  - Reaction of histamine (Hst) with tetrabromophthalic anhydride and protection of
      its imidazole moiety with tritylsulfenyl chloride, followed by hydrazinolysis,
      afforded N-1-tritylsulfenyl histamine, a key intermediate which was further
      derivatized at its aminoethyl moiety. Reaction of the key intermediate with 4
      tosylureido amino acids/dipeptides (ts-AA) in the presence of carbodiimides,
      afforded after deprotection of the imidazole moiety, a series of compounds with
      the general formula ts-AA-Hst (ts=4-MeC(6) H(4) SO(2) NHCO). Some structurally
      related dipeptide derivatives with the general formula ts-AA1-AA2-Hst, were also
      prepared, by in a similar way to the amino acyl compounds mentioned above. The
      new derivatives were examined as activators of three carbonic anhydrase (CA)
      isozymes, hCA I, hCA II (cytosolic forms) and bCA IV (membrane-bound form).
      Efficient activation was observed against all three isozymes, but especially
      against hCA I and bCA IV, with affinities in the 1-10 nanomolar range for the
      best compounds. hCA II was on the other hand activatable with affinities around
      20-50 nM. This new class of CA activators might lead to the development of
      drugs/diagnostic agents for the CA deficiency syndrome, a genetic disease of
      bone, brain and kidneys.

PMID- 10938541
TI  - An endogenous inhibitor of Ca++-ATPase from human placenta.
AB  - Intracellular free calcium is regulated by Ca(++)-ATPase, one form present on the
      plasma membrane (PM Ca(++)-ATPase) and the other on sarcoplasmic (endoplasmic)
      reticulum (SR/ER Ca(++)-ATPase). An endogenous inhibitor of SR Ca(++)-ATPase from
      human placenta was shown to be present in normal placenta and the activity was
      not detectable in placenta from preeclamptic patients. The inhibitor was
      distributed in cytosol and microsomes. The inhibition of Ca(++)-ATPase by this
      inhibitor was concentration- and time-dependent. The inhibitor neither bound to
      DEAE- nor CM-sepharose resins at pH 7.5 and 8.5. Furthermore, it was heat stable
      for 15 min up to 55 degrees C and completely destroyed at 80 degrees C in a few
      minutes. It was also observed to be stable at room temperature for at least 3
      months. The purification and characterization of this inhibitor would be valuable
      in achieving an understanding of the normal regulation of Ca(++)-ATPase in the
      placenta during pregnancy.

PMID- 10938542
TI  - Cadmium inhibition of a structural wheat peroxidase.
AB  - The major peroxidase from 15-day-old wheat plants was purified to homogeneity by
      FPLC ion exchange and molecular exclusion chromatography. It consists of a single
      polypeptide of M(r) 37,500 according to gel filtration and SDS-PAGE and has a pI
      of 7.0. Kinetics of pyrogallol peroxidation showed that the enzyme follows the
      accepted mechanism for peroxidase, with kinetic constants k(1) =4.4x10(6) M(-1)
      s(-1) and k(3) =8.6x10(5) M(-1) s(-1). The effect of different metal ions was
      assayed on peroxidase activity. None of the ions used had any effect on enzyme
      activity, except for Cd(II), which was an inhibitor. This was an unexpected and
      novel finding for a peroxidase. The kinetics of pyrogallol peroxidation at
      different concentrations of Cd(II) have been studied and a mechanism for Cd(II)
      inhibition proposed. The results obtained could explain, in part, cadmium-induced
      oxidative stress.

PMID- 10938543
TI  - Carbonic anhydrase inhibitors. metal complexes of 5-(2-chlorophenyl)-1,3,4
      thiadiazole-2-sulfonamide with topical intraocular pressure lowering properties:
      the influence of metal ions upon the pharmacological activity.
AB  - Metal complexes of a sulfonamide possessing strong carbonic anhydrase (CA)
      inhibitory properties, 5-(2-chlorophenyl)-1,3,4-thiadiazole-2-sulfonamide
      (chlorazolamide) have been obtained from the sodium salt of the sulfonamide and
      the following metal ions: Mg(II), Zn(II), Mn(II), Cu(II), Co(II), Ni(II), Be(II),
      Cd(II), Pb(II), Al(III), Fe(III) and La(III). The original sulfonamide and its
      complexes were assayed for the in vitro inhibition of three CA isozymes, CA I,
      II, and IV, some of which play a critical role in ocular fluid secretion. All
      these compounds (the sulfonamide and its metal complexes) behaved as powerful
      inhibitors against the three investigated isozymes. The parent sulfonamide
      possessed an extremely weak topical pressure lowering effect when administered as
      a 1-2% suspension into the rabbit eye, but some of its metal complexes, such as
      the Mg(II), Zn(II), Mn(II) and Cu(II) derivatives, lower intraocular pressure
      (IOP) in experimental animals very well. Ex vivo data showed a 99.5-99.9% CA II
      inhibition in ocular fluids and tissues of rabbits treated with these agents,
      proving that the observed IOP lowering is due to CA inhibition. The influence of
      the different metal ions upon the efficiency of the obtained complexes as
      pressure lowering drugs are discussed, leading to the possibility of designing
      more selective/potent pharmacological agents from this class.

PMID- 10938544
TI  - Dual substrate model for novel approach towards a kinetic study of
      acetylcholinesterase inhibition by diazinon.
AB  - Limited reports as compared to other insecticides appear in the literature for
      acetylcholinesterase (AChE) inhibition by diazinon. In the current study, new
      kinetic parameters of AChE inhibition by diazinon have been investigated. The
      assay was done with bovine retinal AChE using two different substrate (ASCh)
      concentrations in the absence and presence of diazinon (0.08-1.28 mM). The
      optical density was monitored up to 25 min (reaction time) for the assay. New
      kinetic parameters k'(oms), K'(sms), k(oms), K(sms), K'(asms) and K(asms) ) were
      calculated from these experimental data.

PMID- 10938545
TI  - Functional interactions between GTP cyclohydrolase I and tyrosine hydroxylase in
      Drosophila.
AB  - Tyrosine hydroxylase requires the regulatory cofactor, tetrahydrobiopterin, for
      catecholamine biosynthesis. Because guanosine triphosphate cyclohydrolase I is
      the rate limiting enzyme for the synthesis of this cofactor, it has a key role in
      catecholamine production. We show that GTP cyclohydrolase and tyrosine
      hydroxylase (TH) are co-localized in the Drosophila central nervous system.
      Mutations in the Punch locus, which encodes GTP cyclohydrolase, reduce TH
      activity; addition of cofactor to crude extracts could not fully rescue this
      activity in all mutant strains. The decrease in TH activity and the inability to
      increase it with added cofactor is not due to loss or decreased production of TH
      protein. We found that TH co-immunoprecipitated with GTP cyclohydrolase when wild
      type head extracts were incubated with anti-GTP cyclohydrolase antibody. We
      suggest that regulation of TH by its cofactor may require its association with
      GTP cyclohydrolase, and that the ability of GTP cyclohydrolase to associate with
      TH and its role in tetrahydrobiopterin synthesis may be separable functions of
      this enzyme. These results have important implications for understanding
      catecholamine-related neural diseases and designing strategies for gene therapy.

PMID- 10938546
TI  - A new assay for the genetic study of general anesthesia in Drosophila
      melanogaster: use in analysis of mutations in the X-chromosomal 12E region.
AB  - We describe a new measure of the influence of general anesthetics on Drosophila
      that uses the robust tendency of fruit flies to briskly walk upwards after being
      tapped down. We expose flies to a fixed concentration of anesthetic gas in a 50
      ml tube for a period of up to 1 h and then test the distribution of flies in the
      tube shortly after tapping them to its bottom. By measuring the effect of a
      series of anesthetic concentrations on the fraction of flies that fail to climb,
      we derive quantitative descriptors of the potency of the drug. This "distribution
      test" is superior to previous assays of anesthetic potency in terms of ease and
      reliability. We have used the assay to further the genetic analysis of several
      mutations that cluster on the X chromosome and are known to influence both neural
      function and anesthesia sensitivity. The results establish complementation
      patterns between the mutations, refine their genetic map positions, and open the
      way for the molecular identification of the relevant gene(s).

PMID- 10938547
TI  - Olfactory adaptation in Drosophila larvae.
AB  - To accommodate both high sensitivity as well as the ability to respond to a broad
      range of stimulus concentrations, an organism must possess some means of
      modulating the gain of its sensory systems. This phenomenon is known as
      adaptation. Here, we demonstrate that Drosophila larvae can adapt to three
      odorants in a behavioral paradigm. Larval olfactory adaptation is concentration-
      and dose-dependent. Olfactory and visual adaptation in Drosophila melanogaster
      adults is dependent on the transient receptor potential (trp) calcium channel.
      Recovery from olfactory adaptation, which is TRP-dependent in adults, is shown to
      be unaffected by a loss-of-function trp mutation in larvae. Moreover, the TRP
      gene product is not expressed in the larval olfactory organs. These observations
      suggest a role for trp in mediating sensory function that is conserved between
      sensory modalities in adults but is not conserved between developmental stages.

PMID- 10938548
TI  - Human Auditory Fast and Slow Omitted Stimulus Potentials and Steady-State
      Responses.
AB  - Two kinds of omitted stimulus potentials (OSP) are called "fast" and "slow." Fast
      OSPs, recently found with visual stimuli, are here extended to auditory; they
      occur after omissions or after the end of trains of 1 to >20 Hz clicks. Slow
      OSPs, long known, follow trains of 0.3 to 4 Hz. Each has its constant peak
      latency after the due-time of the first missing stimulus, as though the system is
      expecting something quite accurately on schedule. They differ in dynamics and
      slow OSPs require the subject to attend; fast OSPs do not. Steady-state responses
      (SSR) at a critical click rate of 6-7 Hz sometimes appear to alternate between
      two forms and OSPs may depend on which they follow. Fast OSPs can occur to the
      first, second and even the third omissions after the end of a train. Short
      conditioning periods suffice. Irregular interstimulus intervals do not reduce
      fast OSPs but attenuate slow OSPs.

PMID- 10938549
TI  - Tactual Recognition of Cognitive Stimuli : Roles of Hemisphere and Lobe.
AB  - Four groups of focal brain-damaged patients, involving left and right hemisphere
      damage with or without the involvement of parietal lobe, and a control group of
      general medical patients, were required (a) dichaptically to perceive two
      cognitive stimuli (letter-letter, figure-figure, or letter-figure), and (b)
      haptically match the target stimulus from a set of test stimuli. The number of
      trials taken to match the target stimulus correctly was the dependent measure.
      The significant main effect of lobe suggested that the parietal lobe is the
      primary locus for tactual recognition. All interaction effects involving lobe
      were nonsignificant. The main effect of hemisphere was nonsignificant, although
      the interaction of hemisphere x lobe was significant. Left and right hemisphere
      damaged patients required more trials to recognize "letter" and "figure",
      respectively.

PMID- 10938550
TI  - Sex Differences in Hemisphere Preference As Assessed by a Paper-and-Pencil Test.
AB  - The present study examined sex differences in hemisphere preference (HP) assessed
      by the Preference Test (PT). This instrument is designed to measure the extent to
      which normal subjects rely on right-hemisphere or left-hemisphere cognition.
      Factor analysis on the total sample (N=1,057; 473 men and 584 women) revealed a
      clear two-factor structure (i.e., left-HP and right-HP), although separate
      analyses for men and women suggest that this structure is more straightforward in
      men than in women. The main differences between men and women have to do with PT
      items relevant to language abilities, where women tend to be more symmetrically
      distributed across the two factors. However, the frequency of right- and left-HP
      is similar in men and women and does not change for men when PT scores are
      recalculated after removal of unspecific items. Furthermore, once the items that
      assess verbal abilities were excluded, the corrected PT value for women showed
      higher right-HP. Our results provide some indications of a less pronounced
      lateralization of hemisphere-linked cognitive abilities in women.

PMID- 10938551
TI  - Formant Pattern Ambiguity of Vowel Sounds.
AB  - The formant frequencies of a particular vowel vary according to the speaker group
      and to coarticulation. Therefore, overlapping formant patterns of different
      vowels are commonly related to sex and age differences and to coarticulation, and
      are considered to concern mainly the F(1) -F(2) pattern of adjacent vowels.
      However, several studies have reported indications of a correlation between the
      lower formant frequencies and F(0), as well as of the appearance of different
      formant numbers relevant to vowel identity. As a consequence, the overlap between
      formant patterns of different vowels might be more substantial than has
      traditionally been assumed. Within the present study, therefore, the extent to
      which a given formant pattern can represent different vowels was investigated for
      natural Swiss German vowels produced monotonously and in isolation by men, women
      and children at F(0) of 85-870 Hz. Similar formant patterns were found for
      vocalizations of different vowels with both small and large phonetic distances,
      and within the entire frequency ranges of the formants relevant for phoneme
      identity. For vowel sounds displaying ambiguous formant patterns, the main
      spectral characteristics related to differences in their perceptual identity were
      found to concern F(0) and relative formant amplitudes. Results are given in
      exemplary vowel series, and consequences for the psychophysics of the vowel are
      discussed.

PMID- 10938552
TI  - Pure Consciousness: Distinct Phenomenological and Physiological Correlates of
      "Consciousness Itself"
AB  - This paper explores subjective reports and physiological correlates of the
      experience of "consciousness itself" - self awareness isolated from the processes
      and objects of experience during Transcendental Meditation practice.
      Subjectively, this state is characterized by the absence of the very framework
      (time, space, and body sense) and content (qualities of inner and outer
      perception) that define waking experiences. Physiologically, this state is
      distinguished by the presence of apneustic breathing, autonomic orienting at the
      onset of breath changes, and increases in the frequency of peak EEG power. A
      model, called the junction point model, is presented that integrates pure
      consciousness with waking, dreaming, or sleeping. It could provide a structure to
      generate a coherent program of research to test the full range of consciousness
      and so enable us to understand what it means to be fully human.

PMID- 10938553
TI  - Pretraining Exposure to Physiologically Patterned Electromagnetic Stimulation
      Attenuates Fear-Conditioned Analgesia.
AB  - The effect of weak electromagnetic stimulation on the emergence of conditioned
      analgesia was examined in the adult rat. Subjects were conditioned to associate a
      continuous 20 kHz ultrasonic tone (CS) with 0.2 mA footshock (UCS(-) ) over five
      successive days. For 30 min either before or after conditioning sessions, rats
      were exposed to sham or pulsed (primed burst potentiation) magnetic fields (500
      nT). At the end of the conditioning phase, all animals were evaluated for
      anticipatory analgesia following CS presentation using a hotplate analgesiometer.
      Data analysis suggested a statistically significant attenuation of fear
      conditioned analgesia in rats exposed to electromagnetic stimulation prior to
      conditioning, whereas post-conditioning exposure potentiated the reduction in
      pain sensitivity compared to baseline measures. The present results suggest that
      the emergence of fear-conditioned responses is sensitive to whole body exposure
      to a magnetic field pattern that has been shown to induce long-term potentiation
      in hippocampal slices.

PMID- 10938554
TI  - Effects of Intracortical Microstimulation and Vestibular Stimulation on Pelvic
      Floor Muscles in the Cat.
AB  - Experimental anatomical data in primates and transcranial stimulation of the
      motor cortex in humans indicate that this region projects to pelvic floor
      musculature. We investigated this problem in intact, anesthetized cats with
      intracortical microstimulation (ICMS). Further, we explored the characteristics
      of projection to pelvic floor muscles from the lateral vestibular nucleus of the
      brainstem. ICMS reliably produced responses from both recorded muscles, levator
      ani (LA) and external ani sphincter (EAS). Responses could be obtained both from
      ipsi and contralateral sides, being shorter for the contralateral ones. In
      contrast, vestibular stimulation activates only the EAS. It is proposed that
      these high level inputs to pelvic floor musculature are important for appropriate
      coordination of defecation and micturition.

PMID- 10938555
TI  - Suppression of Experimental Allergic Encephalomyelitis in Rats Exposed
      Nocturnally to Magnetic Fields.
AB  - After inoculation with spinal cord and complete Freund's adjuvant, female Lewis
      rats were exposed to weak, 7 Hz complex magnetic fields or to the control
      condition. The computer-generated magnetic field, whose amplitude varied from 15
      nT to 60 nT every 6 to 12 sec, was presented for 6 min every hour between
      midnight and 0800 of the scotophase. In two replicates of the experiment, the
      rats exposed to the field displayed statistically significant suppression
      relative to sham-field controls (effect size=55%) of the overt symptoms of
      experimental allergic encephalomyelitis which included hindleg paralyses.

PMID- 10938556
TI  - Ventricular Enlargement and the Lithium/Pilocarpine Seizure Model: Possible
      Explanation for Agonistic Behaviour.
AB  - Rats treated with the NMDA-blocker, ketamine hydrochloride 30 minutes after the
      induction of seizures by lithium/pilocarpine exhibited statistically smaller
      lateral ventricles in the left hemisphere compared to rats that had received
      acepromazine after the induction of these seizures. In addition, the ketamine
      treated rats had more neurons and glial cells surrounding the ventricles. These
      results suggest a neuroprotective effect of ketamine, such that there is less
      atrophy surrounding the ventricles and therefore, a smaller degree of dilatation.
      The possibility that insidious neuronal atrophy and death associated with the
      ventricular enlargement encourages the marked aggression in the epileptic rats
      not treated by ketamine is discussed.

PMID- 10938557
TI  - Immune Responses in Nucleus Basalis Magnocellularis-Lesioned Rats Exposed to
      Chronic Isolation Stress.
AB  - The present study was designed to establish the influence of chronic social
      isolation stress on humoral and cellular immunity in nucleus basalis
      magnocellularis (NBM)-lesioned rats. Therefore, ten days after bilateral
      electrolytic lesions of NBM, adult male Wistar rats were immunized with bovine
      serum albumin in complete Freund's adjuvant (BSA-CFA) and placed individually or
      in groups of five rats during 21 days. On days 10 and 21 after immunization, the
      Arthus and delayed hypersensitivity skin reactions to BSA as well as anti-BSA
      antibody production were determined. On day 10, the diameter and intensity of
      delayed hypersensitivity skin reaction to BSA were significantly higher in social
      isolated rats in comparison with the group-reared ones. On day 21, the diameter
      and intensity of the Arthus skin reaction were significantly higher in social
      isolated rats compared to group-reared rats. Between days 10 and 21, the diameter
      and intensity of the Arthus skin reaction significantly increased in social
      isolated rats, while the diameter of delayed hypersensitivity skin reaction
      significantly decreased. In contrast to social-isolated rats, there were no
      significant differences in Arthus and delayed hypersensitivity skin reactions in
      group-reared rats, between days 10 and 21. Also there were no significant
      differences in the production of anti-BSA antibody between social-isolated and
      group-reared rats. The relative spleen weight was significantly lower in social
      isolated rats. These data suggest that chronic isolation stress modify humoral
      and cellular immunity in NBM-lesioned rats.

PMID- 10938558
TI  - Comparison of heteronymous monosynaptic Ia facilitation in young and elderly
      subjects in supine and standing positions.
AB  - BACKGROUND: The control of posture and balance is a primary concern among the
      elderly. Postural instability has been identified as a contributor to the greater
      incidence of falling among this segment of the population. One important
      neuromuscular mechanism identified as important in the control of posture and
      balance is the segmental reflex system. The purpose of this study was to examine
      the role of presynaptic inhibition in modulating the reflex system in young and
      elderly subjects. METHODS: To estimate the influence of body position on
      presynaptic inhibition to the soleus motor pool between young and elderly
      subjects, 11 young (mean age=23.9 yrs.) and 9 elderly (mean age=72.1 yrs.)
      subjects were examined in two different body positions: supine and standing. This
      study utilized the heteronymous facilitation protocol, as described by Hultborn
      et al. (1987), to estimate presynaptic inhibition of the Ia afferent pathway onto
      the soleus alpha-motoneuron pool. Maximal soleus H-reflex (H-max) and motor
      response (M-max) amplitudes were determined prior to testing at each condition,
      and the H-max/M-max ratio at each body position was determined. To estimate
      presynaptic inhibition at each body position, subjects received 24 test soleus H
      reflex stimuli ( approximately 15% M-max), and 24 soleus H-reflexes conditioned
      by stimulation of the ipsilateral femoral nerve. RESULTS: Results demonstrated a
      significant decrease in H-max/M-max ratio from supine (66.1%) to standing (56.8%)
      for the young subjects, whereas the elderly subjects demonstrated no changes in
      the H-max/M-max ratio between body positions (39.8% supine; 39.8% standing). The
      conditioning stimulus produced a significant change in the test reflex for the
      young subjects during supine testing (51.1% increase) but not standing (3.4%
      increase). The elderly subjects demonstrated no significant changes in the test
      reflex produced by the heteronymous conditioning at either condition (17.6%
      increase supine; 4.9% increase standing). CONCLUSIONS: These results demonstrate
      differential effects of both H-reflex modulation and heteronymous conditioning
      for elderly subjects when compared with young adults. These differences may be an
      adaptive phenomenon of the aging neuromuscular system, exemplified by a decreased
      ability to modulate the reflex system in the elderly group.

PMID- 10938559
TI  - Brief communication; differential effects of a physiologically patterned low
      intensity agent on the formation of an olfactory memory trace.
AB  - Male rats were exposed to a low-intensity (300-500 nT) electromagnetic (EM) field
      designed to simulate primed burst potentiation (PB) for 30 min preceding a one
      trial olfactory learning task involving two brief encounters with a juvenile rat
      during a baseline (reference) and an experimental (EM) trial. The amount of time
      spent engaged in behaviors defining social investigation (i.e., sniffing,
      grooming) during the second encounter of the experimental trial was significantly
      elevated in adult rats receiving continuous EM stimulation prior to the initial
      encounter. These results support the hypothesis that LTP-like stimulation
      disrupts the acquisition of a learning task if the stimulus is delivered before
      training.

PMID- 10938560
TI  - Unilateral hippocampal damage impairs spatial cognition in rats.
AB  - Unilateral temporal lobectomy to treat seizure disorders in humans often results
      in cognitive impairment after the surgery. To determine the potential utility of
      a rodent model of unilaterally induced cognitive deficits, the present experiment
      evaluated spatial cognition in adult rats after either left or right hemisphere
      lesioning of temporal neocortex and underlying hippocampal regions. Evaluation of
      performance in the eight arm radial maze revealed that both lesioned groups
      committed more reference memory errors than did nonoperated controls. Working
      memory errors did not differ statistically between groups. The production of a
      spatial learning deficit by unilateral damage suggests that this rodent model
      could serve to test potential improvements in interventional strategies aimed at
      attenuating cognitive effects of the surgical treatment.

PMID- 10938561
TI  - Effects of streptozotocin-induced diabetes and pentylenetetrazol-induced seizure
      on brain cortex (Ca2+)ATPase activity in rats.
AB  - The aim of the present study was to obtain information about the effects of
      pentylenetetrazol-induced status epilepticus (SE) and streptozotocin-induced
      diabetes on brain cortex Ca(2+)ATPase activity. Treatment with pentylenetetrazol
      (PTZ) and streptozotocin (STZ) to rats resulted in significant decrease in brain
      cortex Ca(2+)ATPase activity as compared with controls. However, PTZ-treated
      diabetic rats had a slight but non-significant decrease in enzyme activity.
      Treatment with PTZ caused a more pronounced effect in inhibiting enzyme activity
      than that of treatment with STZ. Our results concluded that reduced brain cortex
      Ca(2+)ATPase activity following PTZ and STZ treatments to rats, may be an initial
      biochemical lesion which triggers a sequence of events which may culminate in
      cell death.

PMID- 10938562
TI  - Modulation by extracellular pH of GABAA receptors expressed in Xenopus oocytes
      injected with rat brain mRNA.
AB  - Rat brain poly(A)(+) mRNA was injected into Xenopus oocytes. After 72-96 hr,
      GABA(A) receptors expressed in this heterologous system were studied by perfusion
      of GABA and recording of GABA evoked chloride current under voltage-clamp
      conditions. The GABA activated currents were blocked by bicuculline and enhanced
      by flunitrazepam. Acidic (6.4) extracellular pH (pH(e) ) augmented, whereas basic
      pH (8.4) decreased the current evoked by 100 microM GABA in the respect of the
      current evoked at pH 7.4. Concentration-response curves for GABA evoked chloride
      currents were built at the three pHs. These data showed that acidic pH does not
      change the EC50 for GABA but it increases significantly I(max) in comparison to
      pH 7.4. At pH 8.4 there was a significant decrease of EC50 for GABA. However,
      there was also a very strong decrease of I(max), so that the overall effect at
      100 microM GABA was a decrease of GABA activated chloride current in the respect
      of the one activated at neutral pH. These data may indicate that on average brain
      GABA(A) receptors are positively modulated by extracellular acidosis. The
      opposite may occur in extracellular alcalosis.

PMID- 10938563
TI  - Antisense oligonucleotide sequences targeting the muscarinic type 2 acetylcholine
      receptor enhance performance in the Morris water maze.
AB  - Blocking autoinhibitory muscarinic type 2 (m2) acetylcholine receptors in the
      central nervous system may increase the release of acetylcholine and improve
      learning and memory. Antisense oligonucleotides (OGNs) complementary to m2
      receptor mRNA were synthesized and evaluated for their efficacy at decreasing
      receptor number and reversing deficits in a cognitive task. Three antisense OGNs,
      which decreased m2 receptor binding in NG108-15 cells, were continuously infused
      into the lateral cerebral ventricle of rats for 6 days at a rate of 0.5 micro1/h
      and a daily dose of 72 microg. Performance in the Morris water maze was compared
      to groups receiving control OGNs or vehicle alone. Decrements induced by 0.2
      mg/kg of scopolamine i.p. were significantly reversed by 2 of the 3 antisense
      OGNs. Use of antisense OGNs targeting the m2 receptor may be a new strategy to
      increase cholinergic neurotransmission and improve learning and memory.

PMID- 10938564
TI  - Application timing of complex magnetic fields delineates windows of posttraining
      pretesting vulnerability for spatial and motivational behaviors in rats.
AB  - Male Wistar rats were trained in a two-session-per-day, non-matching-to-sample
      radial maze task. During the 2 hr interval between training sessions and testing
      sessions subjects were exposed for 60 min to either sham fields or to a low
      intensity (200 to 500 nT) electromagnetic (EM) complex pattern whose electrical
      (current) equivalent has been shown to elicit long-term potentiation (LTP) in
      hippocampal slices. This pattern was applied either immediately following the
      training sessions or immediately antecedent to the testing sessions. Exposures to
      the experimental field immediately following the training session were associated
      with an impairment in spatial memory as inferred by increased commissions of
      reference errors. Exposures immediately prior to the testing session were
      associated with decreased motivation as inferred by a reduction in speed of
      responding. These results suggest that the timing of the presentation of
      patterned magnetic fields may differentially affect the representations of habit
      strength and drive within the consolidating memory trace.

PMID- 10938565
TI  - NK cell and CTL activities can be raised via conditioning of the CNS with
      unrelated unconditioned stimuli.
AB  - Poly I:C, an inducer of interferon alpha and beta, and arecoline, a cholinergic
      muscarinic agonist, were used as unconditioned stimuli in conjunction with
      camphor odor to condition the augmentation of natural killer (NK) cell and
      cytotoxic T lymphocyte (CTL) activities. This observation suggested that two
      unrelated unconditioned stimuli might be used to associate the signals, and
      induce mediators at recall that can raise natural killer cell activity. In
      animals stimulated with an alloantigen to induce CTL, we observed that either
      poly I:C or arecoline conditioned association, and recall with the same CS raised
      CTL activity. It appears that conditioning with different substrates can raise
      either native (NK cell activity) or acquired (CTL activity) immunity. The studies
      suggest that communication between the CNS and NK cells or CTL appear to take
      place through a common pathway(s).

PMID- 10938566
TI  - Can an electronic device improve mood and well-being, and decrease anxiety?
AB  - This study used a double-blind crossover design to investigate the effect of a
      small electronic device, the Quantum Companion, on mood, quality of life and
      anxiety levels. Thirty-four subjects were stratified on age, sex, and current
      stress levels and randomly assigned to receive either a placebo or a Quantum
      Companion, and then after a two week "recovery period," the other instrument.
      Standardized tests were administered before and after each two-week experimental
      period, along with an open ended questionnaire of other life-events during the
      past two weeks. The two weeks with the placebo were marked by (1) more immediate
      positive and fewer immediate negative effects, (2) greater reductions in anxiety,
      and (3) nonsignificant improvement in mood and quality of life, compared to the
      two-week Quantum Companion periods. This study brings out the power of a placebo
      for changing mood, and the importance of using rigorous designs to test claims.

PMID- 10938567
TI  - Lack of impairments on leftward and rightward line extension tasks in neglect
      patients.
AB  - We asked 16 right-brain damaged patients with left unilateral neglect, 9 right
      brain damaged patients without neglect and 11 healthy control subjects to bisect
      horizontal lines or to extend them rightward or leftward. Although in the line
      bisection task patients with neglect showed the typical rightward deviation of
      the subjective line midpoint, they did not show any significant difference when
      compared to the other two experimental groups in both rightward and leftward line
      extension tasks. These results suggest that neglect for the left side of space is
      usually observed in tasks requiring an automatic lateral orienting of attention,
      but not in tasks in which this lateral orienting is submitted to a continuous
      intentional control.

PMID- 10938568
TI  - Concurrent validity and analysis of learning curves on the memory scales of the
      Luria-Nebraska Neuropsychological Battery-Third Edition.
AB  - The purpose of this investigation was to evaluate the concurrent validity of the
      Luria-Nebraska Neuropsychological Battery-Third Edition (LNNB-III) memory scales
      with the WSM-R (study 1), as well as to investigate performance differences
      between brain-injured and nonbrain injured subjects on the LNNB-III memory
      indices, first trial learning, and learning curves of each scale (study 2). Study
      1 had 90 subjects (46 males and 44 females). Study 2 had 228 subjects (109
      normals and 119 brain-injured). Significant correlations were found between the
      LNNB-III memory scales and the WSM-R index scores. Findings also revealed poorer
      overall performance and initial learning of brain-injured subjects across all
      LNNB-III memory scales. Brain-injured subjects also demonstrated significantly
      reduced learning curves across repeated trials on two of the three scales. The
      clinical implications of these findings are discussed.

PMID- 10938569
TI  - General Neuropsychological Deficit Scale sans IQ.
AB  - The General Neuropsychological Deficit Scale (GNDS) of Halstead-Reitan
      Neuropsychological Test Battery (HRNTD) is a summary measure used to
      differentiate brain-damaged from normal subjects. This study seeks to determine
      what happens to the GNDS if the IQ-related items are dropped. A sample of 40
      heterogeneously brain-damaged patients with HRNTB scores was obtained. There were
      36 men and 4 women. All subjects were right-handed except for three left-handed
      men and one ambidextrous male. The sample ranged in age from 16 to 66 years and
      in education from 8 to 22 years. Severity criteria were set for normal, mild,
      moderate, and severe brain damage based on published guidelines from Reitan and
      Wolfson (1992). Dropping the IQ-related items had little effect as 95% of the
      subjects fell in the same impairment severity classification category as before.

PMID- 10938570
TI  - Abbreviated form of the Wisconsin Card Sort Test.
AB  - While the Wisconsin Card Sort Test is a popular procedure used to evaluate
      executive functions, the test may take extended times to administer, especially
      in impaired clients. This has led to interest in the development of a short form
      of the test. Axelrod, Paolo, and Abraham (1997) earlier failed in an attempt to
      develop a short form of the Wisconsin Card Sort Test (WCST). The authors
      suggested that a regression-based approach might work better than their
      predictive model. In a sample of 145 consecutive subjects referred for
      neuropsychological testing, linear and nonlinear regression formulas were
      generated to predict the full 128 card version of the test from 32, 64, and 96
      item versions of the test. Overall, the data obtained strongly suggests that
      multiple regression equations can reliably predict WCST whole test scores from a
      64 or a 96-item version of the test, but not a 32-item version. The results
      indicate that the 64-item version is a clinically sound substitute for the entire
      test.

PMID- 10938571
TI  - Psychophysiological reactivity to stress in nail biters.
AB  - Heart rate and skin conductance were measured for 83 college students (20 male
      nail biters, 19 male non-nail biters, 22 female nail biters, and 22 female non
      nail biters) during baseline, task, and 3 stressors. Psychodiagnostic measures
      included the Beck Depression Inventory and the State-Trait Anxiety Inventory. A
      significant nail-biting status x sex interaction was found in skin conductance
      reactivity (task minus baseline) for all tasks. Male nail biters were
      significantly more reactive than the other 3 groups. There was no significant
      difference in heart rate reactivity in any of the tasks. None of the
      psychodiagnostic measures differentiated among any of the subgroups. Nail biting,
      for males, is associated with psychophysiological changes during stress, although
      the implication of this relationship remains to be clarified.

PMID- 10938572
TI  - Permanent and transient effects of repeated preweaning stress on social and
      sexual behaviors of rats.
AB  - We have reported that exposure of preweaning male and female rats to a model of
      unpredictable mild physical stressors (Neo-A) can decrease the behavioral and
      hormonal responses to acute and chronic stress as adults. In this paper we have
      analyzed the effect of Neo-A on development of social behaviors, including
      aggressiveness, social dominance, and sexual behavior in adulthood. The subjects
      were divided into two groups: Neo-A (daily exposed to unpredictable mild stresses
      from day 2 up to day 15 of suckling; n = 30 litters) and controls (C)
      (undisturbed rats, except for testing, during the same period of life; n = 26
      litters). When day 6 pups were submitted to a social clustering test the Neo-A
      group showed a higher rate of litter-mate clustering than C. The 35 days Neo-A
      males and Neo-A females submitted to a social behavior test after 24 h of social
      isolation also showed higher scores of time spent in active social interaction
      than controls, as well as a higher ratio of animals showing aggressive playing. A
      second social behavior test performed after 48 h of social isolation at days 75
      80 of age revealed that only Neo-A females displayed increased social behavior
      and aggressive behaviors, whereas controls did not. A water competition test
      performed at 24 and 48 h after water deprivation showed that Neo-A adult males
      spent more time in possession of the drinking device and drank more frequently
      than C. When adult proestrous females were exposed to a sexual behavior test, the
      Neo-A group showed shorter latency and higher scores of lordosis quotient. These
      results support the view that exposure to this model of repeated mild stress
      early in life stimulates the development of social behavior, dominance and sexual
      behavior.

PMID- 10938573
TI  - The enhancement of hippocampal primed burst potentiation by
      dehydroepiandrosterone sulfate (DHEAS) is blocked by psychological stress.
AB  - This series of studies investigated the effects of psychological stress and the
      neurosteroid dehydroepiandrosterone sulfate (DHEAS) on hippocampal primed burst
      (PB) and long-term (LTP) potentiation, two electrophysiological models of memory.
      The DHEAS and stress manipulations were performed on awake rats, and then PB and
      LTP were recorded while the rats were anesthetized. DHEAS enhanced PB
      potentiation when administered to rats under non-stress conditions, but had no
      effect when given to stressed rats. Further study showed that DHEAS enhanced PB
      potentiation only when it was administered before, but not after, the rats were
      stressed. The DHEAS and stress manipulations had no effect on LTP. This study
      provides three major findings regarding stress, neurosteroids and hippocampal
      plasticity. First, DHEAS enhanced a threshold form of plasticity (PB
      potentiation), but had no effect on a supra-threshold form of plasticity (LTP).
      Second, stress blocked the DHEAS-induced enhancement of PB potentiation. Third,
      stress and DHEAS effects on the hippocampus were so durable they could be
      performed on awake animals and then be studied while the animals were
      anesthetized. That DHEAS enhanced a subset of forms of hippocampal plasticity
      under restricted behavioral conditions may help to resolve conflicting
      observations of DHEAS effects on cognition and mood in people.

PMID- 10938574
TI  - Attenuation of 8-OH-DPAT-induced decreases in 5-Ht synthesis in brain regions of
      rats adapted to a repeated stress schedule.
AB  - Previously it has been shown that single episode of 2 h restraint produced
      behavioral deficits in rats which were not observed following daily restraint
      period of 2h/day for 5 days. It was suggested that adaptation to a stress
      schedule develops when the similar stress is administered repeatedly. In view of
      a role of 5-hydroxytryptamine (5-HT) in adaptation to stress the present study
      concerns effects of a 5-HT-1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8
      OH-DPAT) on the synthesis of 5-HT in brain regions of rats adapted to a repeated
      restraint stress schedule of 2h/day for 5 days. The drug injected systemically at
      a dose of 1 mg/kg decreased 5-HT synthesis in the hypothalamus, cortex,
      hippocampus, striatum and raphe regions of previously unrestrained rats. These
      decreases were either smaller (raphe) or not observed (hypothalamus, cortex and
      hippocampus) in most brain regions of rats adapted to the repeated restraint
      stress schedule of 2h/day for 5 days. These results suggest that a subsensitive
      negative feedback effect on the synthesis of 5-HT leading to an increase in
      synaptic 5-HT concentration might help coping with stress demand to produce
      adaptation to stress.

PMID- 10938575
TI  - Interactions among chronic cold, corticosterone and puberty on energy intake and
      deposition.
AB  - We have shown that chronic cold stress strongly interacts with corticosterone (B)
      to determine subsequent regulation of the hypothalamo-pituitary-adrenal (HPA)
      axis responses to novel stress. These studies, using the same 2 sets of rats,
      show that chronic cold also interacts with B and testosterone on signals of
      energy balance. The two groups of rats differed in weight by 20% and in age by 2
      weeks (44-59 days of age). Adrenalectomized rats, replaced with varying doses of
      B, were exposed to cold or served as controls. Food intake and body weight during
      the experiments and hormones, metabolites and fat depots were measured on day 5.
      B, but not cold, affected food intake in the younger rats; by contrast, cold, but
      not B, affected food intake in the older rats. Testosterone was higher in older
      control rats and was markedly depressed by cold; younger rats had lower
      testosterone that was minimally affected by cold. Weight gain decreased in all
      rats at room temperature with increasing B, whereas they all lost weight in cold
      independently of B. Cold stimulated and B inhibited interscapular brown adipose
      tissue DNA content (reflecting sympathetic stimulation of thermogenesis). B
      stimulated insulin, whereas cold inhibited leptin and insulin; B also increased
      white adipose tissue weight gain in controls and inhibited its loss in cold.
      Leptin was unrelated to white adipose tissue depots in older control rats but was
      strongly related to these stores in younger rats and in all rats in cold. We
      conclude that: 1. By decreasing signals that act centrally to inhibit food intake
      (insulin, leptin and testosterone) cold allows B to stimulate food intake; 2. B
      inhibits weight gain although it causes accrual of fat; 3. Cold, probably through
      sympathetic stimulation of white adipose tissue, causes fat loss which is
      modulated by the inhibitory effect of B on sympathetic outflow; and, 4. The slope
      of the relationship between fat depot size and leptin becomes flatter in cold,
      possibly because of increased sympathetic outflow to these depots.

PMID- 10938577
TI  - Acute stress persistently enhances estrogen levels in the female rat.
AB  - Here we tested whether exposure to either tailshock or swim stress alters ovarian
      hormone levels, estrogen and progesterone, in females and whether the effects are
      persistent. Adrenal hormone levels were also measured in males and females.
      Estradiol levels were elevated in unstressed females during proestrus relative to
      females in other stages of estrous, and exposure to the stressors enhanced
      estradiol beyond basal levels. For females stressed during diestrus 2, estradiol
      levels were elevated immediately after stressor cessation and up to 24 hrs.
      Exposure to tailshock, but not swim-stress, transiently enhanced progesterone in
      females stressed during the stage of proestrus and estrus. Glucocorticoid levels
      were elevated in response to both stressors and were supraelevated in females
      under both basal and stress conditions relative to males, particularly in blood
      from females exposed to acute swim stress. These results indicate that exposure
      to a relatively acute stressful event immediately and persistently enhances serum
      estradiol and are discussed in the context of reports that exposure to the same
      stressors immediately and persistently impairs associative learning in the female
      rat.

PMID- 10938576
TI  - Short-term effects of postnatal manipulation on central beta-adrenoceptor
      transmission.
AB  - Neonatal handling is known to induce long-lasting changes in behavioral and
      neuroendocrine responses to stress. Since the central noradrenergic system
      participates in the adaptive responses to stressful conditions we have analyzed
      the effects of postnatal handling on beta-adrenoceptor binding sites and
      isoprenaline- and forskolin-stimulated cyclic AMP accumulation in cerebral
      cortex, hippocampus and cerebellum of rats at 1 and 3 months of age. Handled
      animals showed reduced emotional reactivity and lower ACTH and corticosterone
      secretion after stress. Binding studies using [(3) H]CGP12-177 revealed increased
      beta-adrenoceptor binding sites in handled rats in cerebellum and cerebral cortex
      with no changes in hippocampus, and decreased affinity in all cerebral regions.
      Handling reduced basal levels of cyclic AMP in hippocampus and cerebellum but not
      in cerebral cortex. The concentration-response curves of cyclic AMP to
      isoprenaline were displaced to the right in cerebellum of handled rats without
      differences in Emax; however, Emax was significantly reduced in cerebral cortex
      and hippocampus. Direct stimulation of the catalytic subunit of adenylyl cyclase
      by forskolin reduced the efficiency in hippocampus and cerebellum, but not in
      cerebral cortex of handled animals. It is concluded that neonatal handling
      reduces the binding properties of beta-adrenoceptor and its primary biochemical
      responses in the young rat brain, which may account for the reduced
      responsiveness to stress attained in the handled rats, and may explain the
      persistence of the effect. The present study emphasizes the role of the central
      noradrenergic system in modulating the behavioral and neurendocrine responses to
      neonatal handling.

PMID- 10938578
TI  - Corticosterone effects on BDNF mRNA expression in the rat hippocampus during
      morris water maze training.
AB  - Corticosterone and Brain-Derived Neurotrophic Factor (BDNF) have both been shown
      to be involved in spatial memory formation in rats. In the present study we have
      investigated the effect of corticosterone on hippocampal BDNF mRNA expression
      after training in the Morris water maze in young adult Wistar rats. Therefore, we
      first studied BDNF mRNA levels in the hippocampus in relation to corticosterone
      levels at several time points after 4 training trials in the Morris water maze.
      Corticosterone levels were significantly increased after this procedure, and
      hippocampal BDNF mRNA levels only displayed a minor change: an increase in CA1 at
      1 hr after training. However, in a previous study we observed dramatically
      decreased hippocampal BDNF mRNA levels in dentate gyrus and CA1 at 3 hr after
      injection of corticosterone. In order to analyze this discrepancy, we
      subsequently investigated if hippocampal BDNF mRNA expression is affected by
      corticosterone at 3 hr after water maze training. Therefore, we incorporated ADX
      animals and ADX animals which were injected with corticosterone in our study. ADX
      animals which were subjected to water maze training displayed similar hippocampal
      BDNF mRNA levels 3 hr after training compared to control ADX animals.
      Furthermore, ADX animals which were injected with corticosterone showed decreased
      BDNF mRNA levels in all hippocampal regions compared to control ADX animals.
      Water maze training did not alter this effect. Thus, the increased corticosterone
      levels during water maze training do not affect hippocampal BDNF mRNA expression,
      although exogenous corticosterone is effective under these conditions. Hence, our
      results suggest that in this situation BDNF is resistant to regulation by
      endogenous corticosterone, which may be important for learning and memory
      processes.

PMID- 10938579
TI  - Androgens are neuroprotective in the dentate gyrus of adrenalectomized female
      rats.
AB  - Neuroprotective effects of androgens have not been well-characterized, but there
      is evidence that 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-diol) has anti
      seizure effects. To further examine androgens' neuroprotective effects,
      testosterone (T), dihydrotestosterone (DHT), 3 alpha-diol (1.0 mg/kg SC daily),
      or sesame oil vehicle was administered to adrenalectomized or sham-operated,
      young, female Long Evans rats (N = 52). After seven days, animals were perfused
      and trunk blood was collected for radioimmunoassay of plasma corticosterone and
      androgens. No pyknotic cells were seen in the dentate of the sham-operated
      animals or those animals that had incomplete adrenalectomies (n = 20); however,
      cresyl violet and TUNEL stains revealed pyknotic cells in the granule layer of
      the dentate gyrus of adrenalectomized rats (n = 28). Testosterone, DHT, or 3
      alpha-diol significantly reduced the number of pyknotic cells in the dentate
      gyrus compared to vehicle administered, adrenalectomized rats. Steroid
      administered animals had levels of T, DHT, or 3 alpha-diol within physiological
      concentrations. These findings suggest that T, DHT, or 3 alpha-diol may have
      neuroprotective effects via a common mechanism of action.

PMID- 10938580
TI  - Immobilization-induced glutamate efflux in medial prefrontal cortex: blockade by
      (+)-Mk-801, a selective NMDA receptor antagonist.

PMID- 10938581
TI  - Corticosterone effects on BDNF expression in the hippocampus. Implications for
      memory formation.
AB  - The adrenal steroid corticosterone has profound effect on the structure and
      function of the hippocampus. Probably as a result of that, it modulates memory
      formation. In this review, the question is addressed if the corticosterone
      effects on memory processes are mediated by alterations in the expression of the
      neurotrophin Brain-Derived Neurotrophic Factor (BDNF) in the hippocampus. First,
      studies are described investigating the effect of corticosterone on BDNF
      expression in the rat hippocampus. It appears that corticosterone suppresses the
      BDNF expression at the mRNA and protein level in a subfield-specific way. Second,
      a model for the mechanism of action is proposed. In this model, activated
      mineralocorticoid and glucocorticoid receptors repress transcriptional activity
      of the BDNF promoter site-specifically via interaction with other transcription
      factors. Third, the implications for learning and memory are discussed. Studies
      show that during water maze training, corticosterone levels rise significantly,
      but the BDNF expression is not suppressed in any hippocampal subfield.
      Furthermore, high BDNF expression levels in specific subfields correlate with a
      good memory performance. Therefore, we suggest that the resistance of the
      hippocampal BDNF expression to suppression by corticosterone, as seen after water
      maze training, may contribute to an optimal memory performance.

PMID- 10938582
TI  - Substance P is involved in terminating the hypothalamo- pituitary-adrenal axis
      response to acute stress through centrally located neurokinin-1 receptors.
AB  - The neurokinin substance P (SP) has been previously shown to inhibit basal
      hypothalamo-pituitary-adrenal (HPA) axis activity. This study was designed to
      investigate the effects of central injection of the specific neurokinin-1
      receptor antagonist RP67580 on the HPA axis response to acute restraint stress.
      In non-restrained rats injected with RP67580, plasma ACTH and corticosterone
      levels were elevated at 30 and 60 min compared to rats injected with vehicle, but
      there were no differences between vehicle and RP67580 groups at 4h. In restrained
      rats injected with vehicle, plasma ACTH and corticosterone levels were
      significantly elevated at 30 min and 60 min following initiation of the stress
      but had returned to basal levels at 4h. In restrained rats injected icv with
      RP67580, plasma corticosterone and ACTH levels were significantly elevated at 30
      min and 60 min, with no significant differences compared to the restraint
      stressed vehicle-injected group. However, in the RP67580-injected group,
      corticosterone and ACTH levels remained significantly elevated at 4h following
      onset of restraint compared to those in the restraint stressed vehicle-injected
      group. Corticotrophin-releasing factor mRNA levels in the parvocellular
      subdivision of the paraventricular nucleus of the hypothalamus and POMC mRNA
      levels in the anterior pituitary were significantly increased in the stressed
      group 4h following injection with RP67580 compared to the stressed group injected
      with vehicle alone. These data show that endogenous SP does not inhibit the
      initial magnitude of the HPA axis response to restraint stress, but does act
      through neurokinin-1 receptors at a central level to reduce the duration of the
      response to stress. This suggests that SP may be an important central agent
      controlling the transition between acute and chronic stress.

PMID- 10938583
TI  - Long lasting increase in nociceptive threshold induced in mice by forced
      swimming: involvement of an endorphinergic mechanism.
AB  - Mice submitted to forced swimming session(s) displayed a long lasting
      modification in their nociceptive threshold, assessed through their jump latency
      from a hot plate (55 degrees C). Thus two forced swimming sessions (6 min each,
      8h apart), in water at 33 degrees C, increased by about 50% the jump latency when
      the hot plate test was performed 14 hours, 3 days or 6 days thereafter. The water
      temperature (16 degrees C vs 33 degrees C) had no critical influence in this
      respect. To be clearly effective (at 33 degrees C) the swimming session had to be
      performed twice (when performed only once it was irregularly effective); it
      apparently culminated for a 6 min duration, since its effectiveness was not
      significantly increased by extending the swimming time to 12 min or 18 min.
      Performing 2 forced swimming sessions (6 min each, 8h apart), 5 consecutive days,
      resulted in a suppression of the increase in jump latency in the hot plate test.
      The two forced swimming episodes-induced analgesia was prevented by the s.c.
      administration of diazepam (from 0.125 mg/kg) or morphine (from 5 mg/kg) or
      scopolamine (1 mg/kg) before each forced swimming episode. Morphine (7.5 mg/kg)
      was uneffective to prevent the induction of two forced swimming episodes-induced
      analgesia when it was administered immediately after each forced swimming
      session. Finally this analgesia was dose dependently reversed by naloxone (ID(50)
      = 0.14 mg/kg, s.c., 30 min before the hot plate test). It is hypothesized that
      the handling of mice immediately before the hot plate test induces the
      remembrance of the stress induced by previous forced swimming episodes,
      triggering a fear reaction which increases the nociceptive threshold.

PMID- 10938584
TI  - Psychosocial stress and HPA functioning: no evidence for a reduced resilience in
      healthy elderly men.
AB  - In order to investigate if HPA functioning is altered with age, the present study
      was conducted. Fifteen healthy elderly men (60-76 years; mean age 66.5 +/- 1.48
      yrs.) and 12 younger adults (20-29 years; mean age 25.6 +/- 0.77 yrs.) collected
      salivary free cortisol profiles after awakening for basal HPA activity. Then, all
      subjects were exposed to the "Trier Social Stress Test" (TSST). This psychosocial
      stress protocol consists of a free speech and a mental arithmetic task of 13
      minutes duration performed in front of an audience. Beside the assessment of
      endocrine and cardiovascular responses to the stressful task ratings of
      depression, mood and perceived stressfulness were obtained. Results show that
      younger and elderly men had similar morning cortisol profiles after awakening
      with both groups showing the expected rise after awakening (P=0.004). The TSST
      induced significant increases in ACTH, total plasma cortisol, saliva free
      cortisol, and heart rates (all P<0.0001). Regardless of age, both age groups
      showed comparable endocrine response patterns when confronted with the stressor.
      However, cardiovascular responses were significantly higher in younger men
      compared to elderly men (P=0.03). Catecholamine data revealed significant
      norepinephrine and epinephrine increases due to the stressor (both P<0.0001) with
      a trend toward elevated norepinephrine levels in elderly men (P=0.058). In sum,
      the investigated basal and response parameters of HPA functioning neither support
      the idea of a reduced resilience in healthy aged humans nor do they appear to
      strengthen assumptions derived from the so called "glucocorticoid cascade
      hypothesis".

PMID- 10938585
TI  - Galectin-3 decreases in mice exposed to immobilization stress.
AB  - Using M3/38 monoclonal antibody we have analyzed effects of immobilization stress
      on the expression of galectin-3 in liver, spleen and peritoneal macrophages from
      adult RFM and C3H mice, as well as from aged C3H mice (total of 22 animals). In
      all analyzed tissues, immobilization stress caused a significant decrease in the
      expression of galectin-3, ranging from 14% to 47%. The decrease of galectin-3 was
      observed in both strains of mice, as well as in old animals. Moreover, the same
      range of decrease (approximately 50%) was observed when cells grown in vitro were
      exposed to subculturing, or heat-shock. Although the biological significance of
      this effect is not known, it is very interesting that a single episode of
      immobilization stress was sufficient to cause a significant decrease in galectin
      3, implicating that this beta-galactoside-binding lectin might be involved in the
      physiological response to psychological stress.

PMID- 10938586
TI  - The influence of hyperthermic stress on the redox state of glucocorticoid
      receptor.
AB  - Glucocorticoid receptor (GR) is hormone-dependent transcription factor which
      participates in intracellular signal transduction. The reduced state of the
      receptor sulfhydryl groups is considered a necessary prerequisite for its normal
      functioning under the homeostatic conditions. The aim of the work presented in
      this paper was to examine the influence of non-homeostatic conditions - whole
      body hyperthermic stresses at 41 degrees C and 42 degrees C, on GR redox state.
      Non-reducing SDS-PAGE and immunoblot analysis were used to trace alterations of
      the receptor's redox state. The steroid binding assay was performed in order to
      examine direct influence of the whole body heat stresses on the receptor thiols.
      The results obtained show that the 41 degrees C stress leads to formation of
      intermolecular disulfide bonds between apo-GR and associated heat shock proteins
      (Hsp90, Hsp70). Apart from intermolecular GR-Hsp90 and GR-Hsp70 disulfide
      linkages, 42 degrees C hyperthermic stress also caused creation of intramolecular
      ones within GR. The results imply malfunctioning of intracellular redox control
      mechanisms under the hyperthermic conditions.

PMID- 10938587
TI  - Glucocorticoid receptor interaction with Hsp90 remains unaltered after whole body
      hyperthermia.
AB  - The influence of 41 degrees C whole body hyperthermic stress on glucocorticoid
      receptor (GR) association with 90-kDa heat shock protein (Hsp90) in the rat liver
      cytosol was examined. Total cytosolic GR and Hsp90 concentrations, as well as the
      amount of Hsp90 co-immunoprecipitated with the GR were determined by quantitative
      Western blotting using BuGR2 as anti-GR and AC88 as anti-Hsp90 monoclonal
      antibody. After exposure of the animals to the heat stress, the level of
      cytosolic Hsp90 increased, while its ratio to apo-receptor within non-activated
      GR heterooligomeric complexes remained unaltered. Therefore, the Hsp90
      recruitment by the GR was not dependent on Hsp90 total cytosolic concentration.

PMID- 10938589
TI  - Brain MRI findings in cryptococcal meningoencephalitis.

PMID- 10938588
TI  - Nuclear colocalization and complex formation of insulin with retinoblastoma
      protein in HepG2 human hepatoma cells.
AB  - Previous structural and biochemical evidence had suggested that insulin may bind
      to the nuclear tumor suppressor retinoblastoma protein (RB). The present study is
      now the first to unravel the physical and functional interaction between a growth
      factor and an anti-oncoprotein, specifically demonstrating the association
      between insulin and RB in living cells and finding that this complex formation is
      relevant for cell division. Our immunofluorescence microscopy data suggest that
      insulin colocalizes with RB in the cell nuclei of HepG2 human hepatoma cells and
      that contacts the B-region of the RB pocket. Furthermore, these events were found
      to correlate with an enhancement of cell proliferation. These results are in line
      with the initial structure-based predictions and, moreover, provide a suitable
      starting point for the further understanding as well as the pharmacological
      modulation of nucleocrine interactions between growth factors and tumor
      suppressors, in physiology and disease.

PMID- 10938590
TI  - A present state and prospect of future on endoscopic endocrine neck surgery.

PMID- 10938591
TI  - Matrix metalloproteinase and tissue inhibitor of metalloproteinase in human bone
      marrow tissues-an immunohistochemical study.
AB  - Unlike other tissues, bone marrow (BM) seldom displays fibrosis after injury,
      suggesting a possible suppressive mechanism against secondary myelofibrosis in BM
      tissues. We investigated if fibrosis-related factors, such as matrix
      metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP), were
      expressed in BM tissues in vivo. We attempted immunohistochemical studies on
      specimens of 16 BM aspiration materials with normal hematological findings and 21
      BM tissues from autopsy cases who had succumbed to acute heart failure or
      cerebrovascular diseases without any BM injuries. Identification of
      immunohistochemically reactive MMP-2, MMP-9 and TIMP-2 in BM tissue samples
      revealed for the first time that MMP-2 was localized in the myeloid cells,
      erythroblasts and megakaryocytes, MMP-9 in the myeloid cells and megakaryocytes.
      In addition, expression of TIMP-2 in the megakaryocytes as well as in the
      histiocytes within the stroma was verified. In the non-pathological condition,
      MMP/TIMP expressions were not encountered in BM stromal cells, such as
      fibroblasts, vascular endothelial cells, reticulum cells on adipocytes, except
      for TIMP-2 identification in stromal histiocytes. It is highly possible that
      these MMP and TIMP expressions in the BM hematopoietic cells and stromal
      histiocytes are significantly associated with suppression or induction of
      myelofibrosis.

PMID- 10938592
TI  - Proliferating cell nuclear antigen and p53 protein expression in submucosal
      invasive colorectal carcinoma.
AB  - In some cases of early colorectal carcinoma, radical surgical resection might be
      required because of vessel invasion, distant metastasis, or inadequate surgical
      margin. To characterize submucosal invasive colorectal carcinoma, we investigated
      expression of PCNA and p53 protein. Sixty-seven patients who underwent curative
      resection of submucosal invasive colorectal carcinoma participated in this study.
      The PCNA labeling index (PCNA-LI) is determined at the deepest lesion of
      carcinoma. The expression of PCNA and p53 protein were analyzed according to
      clinicopathological factors. 1) The PCNA-LI was correlated to histological grade,
      depth of invasion or vessel invasion in polypoid type. 2) The flat type had
      significantly higher PCNA-LI (65.1+/-8.2%) and p53 protein expression (69.6%)
      than the polypoid type. 3) The PCNA-LI was higher in cases with lymph node
      metastasis than in these without lymph node metastasis. 4) Overexpression of the
      p53 protein was detected in all cases with liver metastasis. Our results suggest
      that in order to determine the treatment for the patients with submucosal
      invasive colorectal carcinoma, the expression of PCNA and p53 protein may be a
      useful biologic marker.

PMID- 10938593
TI  - Morphometrical analysis of the relationship between Helicobacter pylori infection
      and pathological changes of gastric mucosa using Sano's 4 point biopsy method.
AB  - We examined Helicobacter pylori (H. p.) infection and changes in biopsied gastric
      mucosa as observed in biopsy specimens (inflammatory changes and atrophic
      changes) -with reference to their pathophysiological significance. We examined 68
      patients with peptic ulcers and 19 patients with atrophic gastritis as controls.
      We confirmed H. p. infection of the gastric mucosa in biopsies from two points by
      tissue culture, microscopy and urease testing. We examined gastric mucosal flakes
      under microscopy, scoring the inflammatory changes and atrophic changes, from
      biopsies at Sano's 4 points. We compared the gastric mucosal condition of the H.
      p. (+) group and that of the H. p. (-) group histopathologically. The mucosal
      condition of the success fully treated H. p. infection group and that of the
      failure group were also investigated in the same way, as were the conditions
      before and after treatment. RESULTS: 1) The gastric mucosal inflammatory changes
      in the H. p. (+) group were more severe than those in the H. p. (-) group at all
      4 biopsy points. 2) The gastric mucosal atrophy of the H. p. (+) group was more
      severe than that of the H. p. (-) group at all 4 biopsy points. 3) The gastric
      mucosal inflammatory changes in the treatment failure group were more severe than
      those in the Successful treatment group at all 4 biopsy points. 4) The gastric
      mucosal atrophy of the treatment failure group was more severe than that of the
      successful, treatment group at the anterior wall and the posterior wall of the
      body of the stomach. 5) The gastric mucosal inflammatory changes before treatment
      were more severe than those after treatment at all 4 biopsy points. 6) The
      gastric mucosal atrophy before treatment was more severe than that after
      treatment at the antrum and the angle of the stomach. DISCUSSION: H. p. infection
      seemed to cause changes in mucosal condition, severity of gastric mucosal
      inflammation and gastric mucosal atrophy at all 4 of Sano's points.

PMID- 10938594
TI  - Effects of SSM (specific substance maruyama) on HBe antigen-positive chronic
      hepatitis B -clinical efficacy and modulation of cytokines.
AB  - Twenty-three patients with HBe antigen-positive chronic hepatitis B were treated
      with capitalite first letters Maruyama (SSM). HBe antigen turned negative in 15
      patients. The levels of various cytokines in pre- and post-treatment frozen serum
      samples from six patients whose HBe antigen turned negative and from five whose
      HBe antigen did not were examined. Reduction of serum interleukin (IL) -10 level
      to below 20 pg/ml was observed after SSM treatment in four of the six patients
      whose HBe antigen turned negative. SSM was found to stimulate the production of
      interferon (IFN) -gamma in peripheral blood cells from two healthy volunteers.
      This stimulatory effect was confirmed in 12 out of 24 healthy volunteers. SSM
      augmented the production of IFN-gamma in eight out of 10 patients with chronic
      hepatitis B and nine of 10 with hepatitis C. These results demonstrate for the
      first time that SSM stimulates the production of IFN-gamma in human peripheral
      blood cells and also suggest that treatment of HBe antigen-positive chronic
      hepatitis B patients with SSM leads to the clearance of HBe antigen and
      normalization of serum aspartate aminotransferase levels through inhibition of IL
      10 and stimulation of IFN-gamma.

PMID- 10938595
TI  - A case report of insufficiency fracture of the Fossa acetabuli in a patient with
      rheumatoid arthritis.
AB  - Aside from vertebral compression fractures, the most common site of insufficiency
      fractures is the pelvis and lower extremities. In the pelvis, the fractures
      usually occur in the ilium, the pubis and the ischium, but rarely in the fossa
      acetabuli. We report a severe insufficiency fracture of the fossa acetabuli in a
      78-year-old woman with rheumatoid arthritis (RA). She had associated
      insufficiency fractures of the rib, the thoracic spine and the sacrum. In our
      case, senile osteoporosis was present before the onset of the fracture was
      recognized on radiographs, and RA and corticosteroid therapy might have further
      aggravated the porosis, resulting in the destruction of the fossa acetabuli.
      Regarding treatment for the fracture, a cemented total hip replacement without
      bone graft was attempted for several reasons such as the patient's activities,
      postoperative rehabilitation and the bone mass of the acetabulum. The
      postoperative course was satisfactory during study period. However, further
      follow-up is needed to monitor carefully how the patient will be in the future.

PMID- 10938597
TI  - Primary aldosteronism in pregnancy.
AB  - Aldosteronism is a rare complication of pregnancy. We report a case of a 26-year
      old woman who became pregnant soon after a diagnosis of primary aldosteronism due
      to left adrenal adenoma was made. Only oral potassium supplementation was
      required in addition to routine prenatal care until 36 weeks' gestation.
      Subsequently, antihypertensive medication was needed to control elevated blood
      pressure. A healthy male infant was delivered by cesarean section because of
      abruptio placentae. The postoperative course was uneventful. Left adrenalectomy
      was conducted eight months after delivery under laparoscopic visualization. In
      this case report, we discuss management of aldosteronism in pregnancy and review
      the literature.

PMID- 10938596
TI  - Multiple fish vertebra deformity in child with systemic lupus erythematosus: a
      case report.
AB  - We report an 11-year-old female patient with multiple fish vertebra deformity,
      which occurred in the course of treatment with corticosteroids for systemic lupus
      erythematosus (SLE). She was treated for SLE with predonisolone (30 mg per day)
      from April 2, 1996, and presented at our outpatient clinic for an osteoporosis
      check-up on April 27. She was 132 cm tall with-1.7 standard deviation of the
      average height, and X-ray examination revealed no evidence of osteoporosis in the
      spine. Bone mineral density (BMD) was 74.7% of the average BMD. Subsequently, she
      grew to 136 cm in September. However she began to have low back pain (LBP) from
      November, and received alfacalcidol. LBP deteriorated after pulse therapy with
      methylpredonisolone. In June 1997, X-ray examination revealed multiple fish
      vertebra deformity with 58.3% of the average BMD. Moreover her height had
      decreased to 131cm. She underwent combination therapy with elcatonin and
      alfacalcidol. In September 1999, she had no LBP nor progression of fish vertebra
      deformity. However she had no growth in height. Corticoseroids and SLE have
      multiple effects on bone metabolism, making the treatment of porosis complicated
      and difficult.

PMID- 10938598
TI  - Triple-staining to identify apoptosis of hepatic cells in situ.
AB  - To identify apoptosis of nonparenchymal cells in fibrotic livers, we established
      a triple staining method which combined immunohistochemistry for cell markers and
      Masson staining for collagen as well as terminal deoxynucleotidyl transferase UTP
      nick end labeling (TUNEL). Five microm formalin fixed, paraffin-embedded liver
      sections were prepared for staining. Firstly, TUNEL staining was carried out to
      detect apoptosis of liver cells. Then, the sections were subjected to
      immunohistochemistry for alpha-smooth muscle actin (alpha -SMA) or KP-1 to
      identify hepatic stellate cells or Kupffer cells. Finally, Masson staining was
      performed to show the relationship between apoptosis and collagens. In addition,
      we optimized different conditions of fixation, digestion and color development
      which may affect the results.

PMID- 10938599
TI  - Age-related changes in postprandial plasma glucose in type 2 diabetes.

PMID- 10938600
TI  - Creutzfeldt-Jakob disease: the need for vigilance.

PMID- 10938601
TI  - Extracellular matrix and the brain: components and function.

PMID- 10938602
TI  - Mechanisms underlying partial (focal, or lesional) epilepsy.
AB  - Neuronal mechanisms underlying focal convulsions and secondary generalised
      convulsions have been extensively investigated at many different levels, from the
      biochemical, through the cellular to the intact brain. Numerous pathogenic
      processes relevant to epilepsy are now known. Experimental models suggest that
      alterations to the shape, connectivity and receptor-chemistry of individual
      neurons increase their excitability and the resultant increases in activity lead
      to changes of the local ionic environment that further causes enhanced
      excitability. As a consequence of the latter, neuronal firing rates increase and
      there is a shift from single-firing- to burst-firing-behaviours in populations of
      neurons and, possibly, also several changes in the way populations of neurons
      communicate, namely, from 'synaptic' to 'electric' and from orthodromic to
      antidromic. As a consequence, massive neuronal synchronisation occurs, the
      correlate of the focal or secondarily generalised attack. Because of experimental
      difficulties in studying the widespread and evolving neuronal activities in
      freely behaving animals, a precise correlation between states of neuronal
      activation and convulsive behaviour is still unclear.

PMID- 10938603
TI  - Robert Whytt and the pupils.
AB  - Robert Whytt (1714-1766), Professor of the Theory of Medicine in the University
      of Edinburgh from 1745 until his death, was one of the great figures of the early
      years of the so-called Scottish Enlightenment. His investigations of neurological
      phenomena and their mechanisms in animals and humans led him to enunciate what
      was in essence the modern concept of reflex action, although he called the
      phenomenon 'sympathy'. Whytt recognise the peripheral neural mechanisms of the
      reflex arc and demonstrated that its central element occurred in a limited
      segment of the neuraxis, where he invoked an 'inner sentinent principle' to
      mediate neural activity. In 1751, before he had published his formal analysis of
      the reflex arc, Whytt described the direct and consensual pupillary response to
      light and the pupillary response to accommodation. On the basis of some simple,
      well conceived and controlled observations, Whytt showed that the pupillary
      response was not due to a direct effect of light on the uvea or pupillary
      muscles, but involved light acting on the retina, leading to an activation of the
      optic nerve which caused the sentinent principal within the neuraxis to produce
      pupillary constriction via the activity of the nerves to the pupillary muscles.
      Ever since, the pupillary reflex has sometimes been referred to as Whytt's
      reflex.

PMID- 10938604
TI  - Vertebral artery dissection causing stroke in sport.
AB  - Five cases of vertebral arterial dissection occurring in sport are presented.
      These cases emphasise the diagnostic and management difficulties in this setting.
      Stroke in sport, although uncommon, is predominantly due to arterial dissection
      in either the vertebral or carotid arteries. Physicians involved in athlete care
      need to be aware of this diagnosis.

PMID- 10938605
TI  - A study of the functional outcome and mortality in elderly patients with head
      injuries.
AB  - The aim of this study was to determine the functional outcome and mortality in
      relation to the Glasgow coma score (GCS) on presentation in patients aged over 65
      years with acute head injury. 2331 patients with head injury were identified by
      searching the neurosurgery database (1984-1996); 191 met the inclusion criteria
      and systematic review of medical records was undertaken. Functional outcome on
      discharge from hospital and mortality were tested statistically against GCS on
      presentation. Mortality overall was 33. 5%. All 59 patients with GCS <11 on
      presentation had poor outcomes on discharge from hospital. Comparison with
      outcome for the 132 patients with GCS >/=11, of whom 91 had satisfactory
      outcomes, was highly statistically significant (P<0.001). Elderly patients with
      presenting GCS <11 due to acute head injury have poor functional outcomes and
      high mortality rates. Conservative treatment of these patients should be
      considered.

PMID- 10938606
TI  - Aggressive management of aneurysmal subarachnoid haemorrhage based on a
      papaverine angioplasty protocol.
AB  - The aim of this study was to analyse the results of intensive therapy unit
      management of aneurysmal subarachnoid haemorrhage incorporating angioplasty in
      the protocol. Two hundred consecutive patients were treated using a detailed
      protocol that included nimodipine, early aneurysm repair, and surveillance
      angiography. Angiography was performed on days 5 to 7 (or when the clinical state
      suggested the presence of vasospasm). If angiographic vasospasm was identified,
      irrespective of whether clinical vasospasm was present or absent, papaverine was
      selectively administered. In patients with vasospasm blood pressure was elevated
      to 160-180 mmHg and selective papaverine administration was repeated daily until
      vasospasm resolved. In cases requiring more frequent administration of
      papaverine, or in whom papaverine failed to adequately reverse spasm, balloon
      angioplasty was considered and for clinically refractory cases barbiturate coma
      was introduced. 43% of patients underwent papaverine administration and of these
      the average number of separate papaverine procedures was four (maximum 23). 26%
      of patients developed neurological deficits though to be due to vasospasm whilst
      17% underwent papaverine angioplasty without clinical signs of vasospasm. Twelve
      patients (6%) were entered into barbiturate coma. There was a 5.5% mortality and
      no difference in outcome between patients who developed angiographic vasospasm
      and those who did not. For those developing clinical vasospasm, 71% were
      independent and 10% were dead at follow up compared with 84% reaching independent
      grades and 4% dead in those not developing clinical vasospasm. These differences
      failed to reach a significant difference. The average Intensive Therapy Unit stay
      for aneurysmal subarachnoid haemorrhage patients was 13.1 days with a mean cost
      to the hospital of $AUD 24,379. This protocol appears to be both a clinically and
      cost effective method of managing aneurysmal subarachnoid haemorrhage.

PMID- 10938608
TI  - Long term outcome after cervical foraminotomy.
AB  - We recently demonstrated the effectiveness of dorsal foraminotomy in lateral
      herniated cervical disc after 1 year follow-up in a prospective study.(1) The
      goal of this paper is to confirm these results concerning long term outcome. We
      carried out a prospective, consecutive study on 54 patients, operated on for
      lateral herniated cervical disc. We analysed demographic data, the case history,
      the neurological examination on admission and imaging data. Ninety per cent were
      followed up for 3.5 years postoperatively. According to their ratings on a pain
      scale the group were divided into favourable and unfavourable outcomes. These
      groups were analysed in relation to the patient's initial condition. At follow
      up, 90% of patients showed complete recovery or improvement. A long standing
      preoperative neurological deficit seems to be an important prognostic factor for
      unfavourable long term outcome after cervical foraminotomy.

PMID- 10938607
TI  - Apraxia and cerebral haemorrhage: the relationship between haematoma volume and
      prognosis.
AB  - In this study, we examined twenty-five patients with left putaminal haemorrhage
      to investigate the relations between ideational apraxia (IA) and intracerebral
      haemorrhage. Apraxias were determined at 1 and 6 months after the stroke onset.
      Extension and volume of haematoma were examined with CT scan within 2 days of
      stroke onset. IA was present in 10 cases at 1 month and disappeared in 6 cases
      (transient IA) and persisted in 4 cases(persisted IA) at 6 months from the onset.
      Although the haematoma volume related to the existence of IA, there was no
      significant difference between transient and persistent IA. All three patients
      with the haematoma volume larger than 40 ml in the transient IA group were
      younger than 50 years old. All cases with persistent IA were older than 50 years
      old. Consequently, the existence of IA seems to be partially dependent on the
      haematoma volume which may cause the organic damage of subcortical white matter.
      However, patient's age is also important to determine the prognosis of IA. This
      maybe related to the nature of the haemorrhage and the mode of the onset. These
      factors remain to be determined.

PMID- 10938609
TI  - Intrathecal baclofen alleviates autonomic dysfunction in severe brain injury.
AB  - Sympathetic storm phenomena are well known therapeutic problems in patients with
      severe brain injury. We have treated four patients with intrathecal baclofen
      (ITB) who suffered from severe hypertension, tachycardia and other sympathetic
      storm phenomena after different primary events. In all patients conventional
      therapy with sedatives and antiadrenergic medication had been taken to the upper
      limits before initiating ITB. Autonomic dysfunction immediately improved in three
      of four patients. In all patients ITB, via lumbar or ventricular route, proved
      safe and without complications. The anatomical and pharmacological basis of the
      GABA-B agonist action on such sympathetic storm phenomena are not yet fully
      understood. However, the positive results observed in three out of four patients
      are promising and require further investigation. ITB is a new therapeutic
      approach to control otherwise unresponsive sympathetic storm phenomena in severe
      brain injury.

PMID- 10938610
TI  - The effect of pinealectomy on immune parameters in different age groups in rats:
      results of the weekly alteration of the zinc level and the effect of melatonin
      administration on wound healing.
AB  - It is generally accepted that the pineal gland is a neuroendocrine organ. Several
      recent experiments have shown that the pineal gland has functional and anatomic
      connections with many organs and systems, particularly with the immune system,
      and, therefore, the gland is now recognised as an important immunoneuroendocrine
      organ both in man and animals. The present study investigates the effect of
      pinealectomy on some immune parameters including zinc pool alterations and wound
      healing process in different age group in rats and also investigates the effect
      of melatonin administration on wound healing in different age groups. Experiments
      were performed on two different age groups of rats (neonatal and young). We have
      experimentally shown the induction of immune depression by pinealectomy and the
      restorative competence of melatonin administration in the present study. The
      results also showed that the plasma zinc level was significantly reduced in the
      third week after the pinealectomy particularly in pinealectomised neonatal rats
      and the wound healing process affected only in pinealectomised neonatal rats but
      restored to normal by melatonin administration. In view of these data, as
      described previously, the pineal gland has a main regulatory function in immune
      physiology, but our study indicates that only neonatal immune functions are
      significantly affected by pinealectomy.

PMID- 10938611
TI  - Transoral resection of retro-odontoid disc sequestration: case report and review
      of the literature.
AB  - A rare case of retro-odontoid disc sequestration causing significant cord
      compression and progressive neurological deterioration is presented. The clinical
      history, radiology, treatment and pathogenesis of the case are described, along
      with a review of the relevant literature.

PMID- 10938612
TI  - Spoon retractors for soft mass.
AB  - We have designed spoon retractors for removing a soft mass. The retractor is
      composed of a main part which is eggshell like and concave in shape, with sizes
      varying from 5 mm to 4 cm in width, and a flexible shaft. The retractor enables
      retraction to hold a soft mass upward creating an ample space for dissecting it
      from surrounding structures in the depth. The spoon retractor has proven to be
      useful for gliomas and metastatic tumours, particularly for haemorrhagic lesions
      such as haemangioblastomas and arteriovenous malformations, because the retractor
      facilitates an en bloc removal of the mass by retracting it without causing
      laceration or rupture, and with feeding or draining vessels easily visualised.

PMID- 10938613
TI  - Spinal cord herniation into an extradural arachnoid cyst.
AB  - A herniation of the thoracic spinal cord into the mouth of an extradural
      arachnoid cyst is reported in a 37 year old man. This is the 20th case, but the
      first posterior herniation; all the others were anterior. He presented with
      progressive paraparesis and the magnetic resonance imaging (MRI) showed kinking
      of the cord into the cyst. Surgical release of the neck of the hernia was
      successful.

PMID- 10938614
TI  - Synovial chondromatosis of the temporomandibular joint with intracranial
      extension.
AB  - We present a rare case of synovial chondromatosis of the left temporomandibular
      joint with intracranial extension and review the relevant literature. This is the
      sixth published report of such a skull base tumour. We discuss imaging
      characteristics and the differential diagnosis with regards to a curative
      surgical resection.

PMID- 10938615
TI  - Myopathic dropped head syndrome: a syndrome of mixed aetiology.
AB  - We report two patients with myopathic dropped head syndrome, a rare and
      interesting neuromuscular syndrome characterised by a predominant weakness of the
      neck extensor muscles. The first patient, a middle aged Chinese man, presented
      with progressive weakness of neck extension but his clinical course later
      stabilised despite a lack of response to corticosteroids. Muscle biopsy revealed
      a necrotising myopathy with no evidence of inflammation. This patient supports
      the existence of an idiopathic restricted non-inflammatory myopathy, a so called
      isolated neck extensor myopathy syndrome which is recognised to pursue a less
      progressive, more benign course. Our second patient had histopathological
      evidence for polymyositis; there was a favourable response to steroids. Our cases
      underscore the fact that there may be a spectrum of pathological processes
      associated with the myopathic dropped head syndrome ranging from non-inflammatory
      muscle necrosis to a full blown inflammatory myositis.

PMID- 10938616
TI  - Non-ruptured large dorsal internal carotid artery aneurysm presenting with
      temporal quadrantanopsia.
AB  - A 63-year-old woman presenting with temporal lower quadrantanopsia of the right
      eye was found to have a large dorsal internal carotid artery aneurysm. Large
      dorsal aneurysms of the internal carotid artery are rare. Lateral compression of
      the optic nerve by the aneurysm might damage the optic nerve at the medial side
      of the right optic foramen. Direct clipping surgery was performed uneventfully.
      Since the dome of the aneurysm was buried in the frontal lobe and also attached
      to the anterior skull base, a careful approach to the aneurysm with removal of
      the anterior clinoid process and drilling into the planum sphenoidale around the
      aneurysm dome was needed. The surgical strategy is discussed.

PMID- 10938617
TI  - Flaccid quadriplegia from tonsillar herniation in pneumococcal meningitis.
AB  - A young woman with fulminant pyogenic meningitis became quadriplegic, areflexic
      and flaccid due to herniation of the cerebellar tonsils and compression of the
      upper cervical cord. This state of spinal shock was associated with absent F
      waves. Intracranial pressure was greatly elevated and there was an uncertain
      relationship of tonsillar descent to a preceding lumbar puncture. Partial
      recovery occurred over 2 years. Tonsillar herniation can cause flaccid
      quadriplegia that may be mistaken for critical illness polyneuropathy. This case
      demonstrates cervicomedullary infarction from compression, a mechanism that is
      more likely than the sometimes proposed infectious vasculitis of the upper cord.

PMID- 10938619
TI  - Facial pain as a presenting feature of intracerebral haemorrhage.
AB  - A literature review from 1966 using Medline with keywords 'cerebral haemorrhage'
      and 'facial pain' failed to reveal any cases in which facial pain was the initial
      feature of intracranial haemorrhage. The following case describes ipsilateral
      facial pain which is previously undescribed as a presentation of intracranial
      bleeding. A 53 year old female who was previously well, with no significant
      history of headache, developed right facial pain from the orbit to the maxilla.
      Ten to 15 min later she developed nausea and vomiting with unsteadiness and
      confusion. She had difficulty with left-hand fine finger movements, with normal
      sensation and reflexes but an extensor plantar response on the left. Facial pain
      persisted for 3 days. Initial imaging revealed a 4 x 3 cm right temporal lobe
      haemorrhage with mass effect and oedema extending into the subarachnoid space.
      Angiogram revealed a right temporal lobe arteriovenous malformation. The basis of
      the pain remains speculative but includes sensation from the torn vessel wall
      being referred to the face and subarachnoid blood irritation of the meninges in
      the middle cranial fossa. Another possibility is irritation of somatosensory
      cortex II, but why this should result in only ipsilateral pain is unclear. Facial
      pain should be an alerting symptom to the neurologist when it appears with no
      apparent cause.

PMID- 10938618
TI  - Spontaneous cerebral haemorrhage without hypertension in non-mosaic 45X Turner's
      syndrome.
AB  - Cerebral haemorrhage without hypertension, arteriosclerosis or clotting defect
      has not been reported in patients with Turner's syndrome before. In a 51 year old
      female patient with non-mosaic Turner's syndrome, acute aphasia and right-sided
      hemiplegia occurred, due to left-sided basal ganglia haemorrhage. The history for
      hypertension was negative, blood pressure was normal throughout hospitalisation
      as well as during 24 h monitoring, and all tests for secondary hypertension were
      negative. There was no indication of arteriosclerosis or a clotting defect. Since
      there were hypermobile joints, hyperextensible skin and ectatic ascending aorta
      and brachiocephalic trunk on angiography, a general connective tissue defect was
      assumed, making arteries more vulnerable to physiologically increased blood
      pressure and rupture of intracerebral arteries with consecutive bleeding.

PMID- 10938620
TI  - Unruptured aneurysms should generally be clipped.

PMID- 10938621
TI  - Unruptured aneurysms should generally not be clipped.

PMID- 10938623
TI  - Diary of events

PMID- 10938622
TI  - Comment

PMID- 10938624
TI  - News and notices

PMID- 10938625
TI  - Moment expansions in spatial ecological models and moment closure through
      Gaussian approximation.
AB  - We describe the dynamics of competing species in terms of interactions between
      spatial moments. We close the moment hierarchy by employing a Gaussian
      approximation which assumes that fluctuations are independent and distributed
      normally about the mean values. The Gaussian approximation provides the lowest
      order systematic correction to the mean-field approximation by incorporating the
      effect of fluctuations. When there are no fluctuations in the system, the mean
      equations agree with the Gaussian approximation as the fluctuations are weak. As
      the fluctuations gain strength, they influence the mean quantities and hence the
      Gaussian approximation departs from the mean-field approximation. At large
      fluctuation levels, the Gaussian approximation breaks down, as may be explained
      by the bimodality and skewness of the fluctuation distribution of the partial
      differential equation.

PMID- 10938626
TI  - The effect of incubation time distribution on the extinction characteristics of a
      rabies epizootic.
AB  - The continuous model of Anderson et al. (1981), Nature 289, 765-771, is
      successful in describing certain characteristics of rabies epizootics, in
      particular, the secondary recurrences which follow the initial outbreak; however,
      it also predicts the occurrence of exponentially small minima in the infected
      population, which would realistically imply extinction of the virus. Here we show
      that inclusion of a more realistic distribution of incubation times in the model
      can explain why extinction will not occur, and we give explicit parametric
      estimates for the minimum infected fox density which will occur in the model, in
      terms of the incubation time distribution.

PMID- 10938627
TI  - Statistical analysis and parsimonious modelling of dendrograms of in vitro
      neurones.
AB  - The processes whereby developing neurones acquire morphological features that are
      common to entire populations (thereby allowing the definition of neuronal types)
      are still poorly understood. A mathematical model of neuronal arborizations may
      be useful to extract basic parameters or organization rules, hence helping to
      achieve a better understanding of the underlying growth processes. We present a
      parsimonious statistical model, intended to describe the topological organization
      of neuritic arborizations with a minimal number of parameters. It is based on a
      probability of splitting which depends only on the centrifugal order of segments.
      We compare the predictions made by the model of several topological properties of
      neurones with the corresponding actual values measured on a sample of honeybee
      (olfactory) antennal lobe neurones grown in primary culture, described in a
      previous study. The comparison is performed for three populations of segments
      corresponding to three neuronal morphological types previously identified and
      described in this sample. We show that simple assumptions together with the
      knowledge of a very small number of parameters allow the topological
      reconstruction of representative (bi-dimensional) biological neurones. We discuss
      the biological significance (in terms of possible factors involved in the
      determinism of neuronal types) of both common properties and cell-type specific
      features, observed on the neurones and predicted by the model.

PMID- 10938628
TI  - Darwinian aspects of molecular evolution at sublinear propagation rates.
AB  - Mean fitness is non-decreasing in the symmetry sector of the frequency trajectory
      followed in competitive replication at sublinear propagation rates (parabolic
      time course). This sector contains the pairwise symmetric distribution of species
      frequencies and its neighboring states, and represents at least half the possible
      states of an evolving sublinear system. States is the non-symmetry sector produce
      a negative rate of change in mean fitness. The heterogeneous steady state
      attained in a finite sublinear system is destabilized by formation of a variant
      with above-threshold fitness. Evolution in the post-steady-state interval
      elevates the fitness threshold for coexistence. Contrary to the proposition that
      'parabolic growth invariably results in the survival of all competing species',
      only species with sufficient fitness to avoid subthreshold fitness survive.

PMID- 10938629
TI  - A Hodgkin-Huxley model exhibiting bursting oscillations.
AB  - We investigate bursting behaviour generated in an electrophysiological model of
      pituitary corticotrophs. The active and silent phases of this mode of bursting
      are generated by moving between two stable oscillatory solutions. The bursting is
      indirectly driven by slow modulation of the endoplasmic reticulum Ca2+
      concentration. The model exhibits different modes of bursting, and we investigate
      mode transitions and similar modes of bursting in other Hodgkin-Huxley models.
      Bifurcation analysis and the use of null-surfaces facilitate a geometric
      interpretation of the model bursting modes and action potential generation,
      respectively.

PMID- 10938631
TI  - Individual- and population-based diversity in restriction-modification systems.
AB  - Restriction-modification (RM) systems are cognate gene complexes that code for an
      endonuclease and a methylase. They are often thought to have developed in
      bacteria as protection against invading genetic material, e.g., phage DNA. The
      high diversity of RM systems, as observed in nature, is often ascribed to the
      coevolution of RM systems (which 'invent' novel types) and phages. However, the
      extent to which phages are insensitive to RM systems casts doubts on the
      effectiveness of RM systems as protection against infection and thereby on the
      reason for the diversity of RM systems. We present an eco-evolutionary model in
      order to study the evolution of the diversity of RM systems. The model predicts
      that in general diversity of RM systems is high. More importantly, the diversity
      of the RM systems is expressed either at the individual level or at the
      population level. In the first case all individuals carry RM systems of all
      sequence specificities, whereas in the second case they carry only one RM system
      or no RM systems at all. Nevertheless, in the second case the same number of
      sequence specificities are present in the population.

PMID- 10938630
TI  - Theory for the feedback inhibition of fast release of neurotransmitter.
AB  - Autoinhibition of neurotransmitter release occurs via binding of transmitter to
      appropriate receptors. Experiments have provided evidence suggesting that the
      control of neurotransmitter release in fast systems is mediated by these
      inhibitory autoreceptors. Earlier, the authors formulated and analysed a
      mathematical model for a theory of release control in which these autoreceptors
      played a key role. The key experimental findings on which the release-control
      theory is based are: (i) the inhibitory autoreceptor has high affinity for
      transmitter under rest potential and shifts to low affinity upon depolarization;
      (ii) the bound (with transmitter) autoreceptor associates with exocytotic
      machinery Ex and thereby blocks it, preventing release of neurotransmitter.
      Release commences when depolarization shifts the autoreceptor to a low-affinity
      state and thereby frees Ex from its association with the autoreceptors. Here we
      extend the model that describes control of release so that it also accounts for
      release autoinhibition. We propose that inhibition is achieved because addition
      of transmitter, above its rest level, causes transition of the complex of
      autoreceptor and Ex to a state of stronger association. Relief of Ex from this
      state requires higher depolarization than from the weakly associated complex. In
      contrast to the weakly associated complex that only requires binding of
      transmitter to the autoreceptor to be formed, the transition to the strongly
      associated complex is induced by a second messenger, which is produced as a
      result of the receptor binding to transmitter. The theory explains the following
      experimental results (among others): for inhibition via transmitter or its
      agonists, the magnitude of inhibition decreases with depolarization; a plot of
      inhibition as a function of the concentration of muscarine (an acetylcholine
      agonist) yields an S-shaped curve that shifts to the right for higher
      depolarizations; the time course of release does not change when transmitter is
      added; the time course of release also does not change when transmitter
      antagonists are added, although quantal content increases; however, addition of
      acetylcholine esterase (an enzyme that hydrolyses acetylcholine) prolongs
      release.

PMID- 10938632
TI  - Modelling run-and-tumble chemotaxis in a shear flow.
AB  - The biased random walk undergone by chemotactic bacteria such as Escherichia coli
      will be influenced at the microscopic level by flow in the ambient medium. In
      this paper, we model swimming bacteria being advected and rotated by a simple
      shear flow. Under certain scaling assumptions, we obtain an advection-diffusion
      equation for cell density, when the chemotactic response is small, which shows a
      coupling between the rotation and chemotaxis. We also present an alternative
      method for calculating the chemotactic flux in an unbounded region which is valid
      for more general chemotactic responses.

PMID- 10938633
TI  - Hispanic ethnicity and risk for combat-related posttraumatic stress disorder.
AB  - Hispanic veterans are said to exhibit higher risk of developing posttraumatic
      stress disorder (PTSD) than veterans of other racial/ethnic backgrounds. This
      prediction is based largely on findings from the National Vietnam Veterans
      Readjustment Study (NVVRS; R. A. Kulka et al., 1990a, 1990b). This article first
      summarizes the findings of the NVVRS with regard to race/ethnicity and PTSD, and
      then it makes a careful assessment of both the external and the internal validity
      of these findings. Conceptual issues are addressed and, where possible, further
      analyses of the NVVRS data set are conducted to identify factors that account for
      ethnic differences in rates of the disorder. Possible mediators of the effects of
      Hispanic ethnicity on vulnerability to PTSD are identified, including
      psychosocial factors (racial/ethnic discrimination and alienation) and
      sociocultural influences (stoicism and normalization of stress, alexithymia, and
      fatalism). Areas in which future research is needed are indicated.

PMID- 10938634
TI  - Culture-specific models of men's sexual aggression: intra- and interpersonal
      determinants.
AB  - The role of intra- and interpersonal variables was examined in samples of Asian
      American (N = 91) and European American (N = 377) men. A path model for Asian
      American men suggested 2 interpersonal paths and 1 intrapersonal path to sexual
      aggression. For Asian Americans, concern about social standing is a risk factor
      among those who hold misogynous beliefs and who use alcohol before sex. Concern
      about the negative reputational impact of sexual aggression is a protective
      factor among Asian Americans who do not hold these negative attitudes. A European
      American model suggested only an intrapersonal path to sexual aggression
      consisting of misogynous beliefs, with interpersonal variables not being
      predictive of sexual aggression. These results suggest both individualist and
      collectivist determinants of Asian American sexual aggression, whereas only
      individualist determinants were found for European American sexual aggression.

PMID- 10938636
TI  - Are personality disorder criteria ethnically biased? A card-sort analysis.
AB  - On the basis of methodology used in previous research on sex criterion bias, this
      study examined ethnicity criterion bias of personality disorders (PDs) defined in
      the Diagnostic and Statistical Manual of Mental Disorders (3rd ed., Rev.) and
      included examination of sex as well as ethnicity. A card-sort analysis using
      undergraduate college students as sorters indicated that criteria for all of the
      PDs were applied disproportionately by ethnicity, resulting in particular ethnic
      groups receiving diagnoses for specific PDs. Criteria were sorted systematically
      such that diagnoses of antisocial and paranoid PDs were assigned to African
      Americans, schizoid PD was assigned to Asian Americans, and schizotypal PD was
      assigned to Native Americans. All other PDs were assigned to European Americans,
      whereas none of the criteria were sorted resulting in any PD diagnosis being
      applied to Latinos. Implications for clinicians, methodological considerations,
      and recommendations for future research are discussed.

PMID- 10938635
TI  - The development of the Cultural Health Attributions Questionnaire (CHAQ).
AB  - Current general health belief measures that are used to assess health behaviors
      do not capture the full range of health beliefs present among Latinos. The
      purpose of this study was to develop a reliable and valid measure of Latino
      health beliefs, the Cultural Health Attributions Questionnaire (CHAQ). Three
      hundred forty participants were recruited in 2 metropolitan areas with large
      Latino populations. Exploratory factor analysis revealed 2 highly interpretable
      12-item subscales: the Equity Attribution and the Behavioral-Environmental
      Attribution scales. Examination of the relationships between the subscales and
      measures of acculturation provided evidence of construct validity. Moreover, the
      prediction of health care behavior by the CHAQ also indicated initial criterion
      validity.

PMID- 10938637
TI  - Cross-ethnic equivalence of the Hopkins Symptom Checklist-21 in European
      American, African American, and Latino college students.
AB  - To determine if the Hopkins Symptom Checklist-21 demonstrates equivalent validity
      across different ethnic groups, the authors tested the factor structure of the
      instrument with a sample of European American (n = 514), African American (n =
      154), and Latino (n = 229) college students using confirmatory factor analysis
      with tests of invariance across groups. For the most part, a 3-factor model with
      Performance, General, and Somatic factors fit equally well for all 3
      racial/ethnic groups. Differences involved only a few items in terms of either
      the strength of a factor loading or an error term. The results generally support
      the validity of the use of the instrument for measurement of distress in these
      different racial/ethnic groups.

PMID- 10938638
TI  - Cultural, contextual, and intrapersonal predictors of risky sexual attitudes
      among urban African American girls in early adolescence.
AB  - The role of cultural factors in explaining sexual attitudes among African
      American urban girls, aged 10-13 years, was investigated in this study. The
      authors predicted that girls with higher school interest, family cohesion,
      religiosity, and behavioral self-esteem would endorse less risky sexual
      attitudes. Also, older girls were expected to have more risky sexual attitudes
      than younger girls, and girls from 1- rather than 2-parent households were
      expected to have more risky sexual attitudes. The authors hypothesized that
      ethnic identity and gender role orientations would contribute to explaining
      variability in sexual attitudes after controlling for contextual and
      intrapersonal variables. A questionnaire containing measures of the study
      constructs was administered to 214 girls who were participants in a substance
      abuse prevention program. Pretest data were used in analyses. A final regression
      model accounted for 23% of the variance in sexual attitudes. Age and behavioral
      self-esteem were significant predictors, with younger teens and teens with higher
      behavioral self-esteem having less risky sexual attitudes. Cultural variables
      contributed to explaining variation in sexual attitudes after other variables
      were controlled for. Higher levels of ethnic identity were associated with less
      risky sexual attitudes. A masculine gender role orientation was associated with
      more risky sexual attitudes.

PMID- 10938639
TI  - [Oromaxillofacial surgery in Europe].
AB  - The recognition of a medical discipline on a European level as an independent
      specialty depends on its registration in the medical directives of the European
      Union. With supreme effort, the oral and maxillofacial surgeons of the EU reached
      this goal in 1989. The UEMS--Section of Stomatology and Oromaxillofacial Surgery-
      became the forum for discussion of the relevant problems with representatives of
      the member states and officials of the European Commission. Thanks to its
      activities, oral and maxillofacial surgery is now recognized as an independent
      specialty with about 3800 specialists in 11 European countries.

PMID- 10938640
TI  - [History of the German Society of Oromaxillofacial Surgery].
AB  - The German Society of Oral and Maxillofacial Surgery was founded by Martin
      Wassmund in 1951. One of the main reasons was the need for scientific
      representation in the council at a medical convention. The Society, originally
      composed of 52 members, was first called "The German Society of Maxillofacial
      Surgery". In 1972, it extended its title to include the term "oral" ("Mund") and
      currently comprises 620 members. A scientific conference is held annually on a
      specific topic. The lectures given there have been published since 1954 in
      "Fortschritte der Kiefer- und Gesichts-Chirurgie" (Progress in Maxillofacial
      Surgery) by Thieme Verlag; since 1997, they have appeared as a Springer-Verlag
      supplement. Topics of choice are published in "Mund-, Kiefer- und
      Gesichtschirurgie" ("Oral and Maxillofacial Surgery"), originally by Hanser in
      Munich and now by Springer-Verlag in Heidelberg. In this manner, it was possible
      to completely document the scientific activities and progress in this specialty.
      Each year since 1957, a prize named after M. Wassmund, has been given for
      outstanding scientific accomplishment. The presidents, convention locations,
      topics, and prizewinners are listed in a table. Since the founding of the Society
      of Oral and Maxillofacial Surgery, close cooperation has existed with the
      National Association of German Oral and Maxillary-Facial Surgeons (Bundesverband
      der Deutschen Arzte fur Mund-Kiefer-Gesichts-Chirurgie). In order to intertwine
      scientific and political interests, a fusion of these two organizations is
      planned for the year 2000.

PMID- 10938641
TI  - [Professional profile of the established oromaxillofacial surgeon].
AB  - To qualify for further specialist training as a maxillofacial surgeon, a licence
      to practice in general medicine as well as a licence to practice in dentistry
      must be obtained beforehand. In addition to the 4-year course to qualify,
      maxillofacial surgeons can gain the additional qualification in the field of
      "plastic surgery" in a further course lasting 3 years. By the end of 1998, there
      were 698 maxillofacial surgeons in private practices in Germany in comparison to
      322 hospital-employed maxillofacial surgeons. Of the work done by maxillofacial
      surgeons (in private practices), 28% is in contracted hospitals; this percentage
      is relatively high in comparison to other disciplines in which private
      specialists use contracted hospitals. It is impossible these days for an
      individual specialist to completely cover all areas of maxillofacial surgery. In
      our field, joint practices with an internal specialization will increase the
      spectrum and quality of treatment in the future and will counteract competition
      from hospital-employed specialists now that day-case surgery has been introduced
      in these hospitals. Further training by the individual will remain an
      indispensable necessity as well as personal involvement by every maxillofacial
      surgeon in the postgraduate medical training of doctors and dentists. This can
      only be achieved if the economic situation of specialists is maintained in health
      politics.

PMID- 10938642
TI  - [The professional profile of the oromaxillofacial surgeon in the clinic].
AB  - The German Society of Oral and Maxillofacial Surgery (Die Deutsche Gesellschaft
      fur Mund-, Kiefer- und Gesichtschirurgie) is celebrating its 50th birthday--an
      occasion to highlight the current professional and political situation and future
      perspectives in the clinics devoted to this specialty. To this end, structural
      data from 71 major clinics (or divisions) are analyzed. The clinics have 2,300
      beds, 32 on average, with a variance width of 10:64. This corresponds to one
      clinic bed for approximately 35,000 inhabitants. The neighborhood of the clinics
      and thus the working conditions and personnel situation have changed markedly in
      the past few years. Working conditions are evident from the doctor-bed proportion
      with its resulting burden on the medical team. There are 244 assistants currently
      studying for their specialty; 107 others are striving for the additional title of
      "Plastic operations". Plans for positions are based less on the planned number of
      beds than on the number of cases, productivity, and treatment spectrum of the
      clinic, sometimes with a bonus for research and teaching. The outpatient sector,
      which plays a major role, is not considered. Health-care politics continue to
      stress budgeting and rationalization, i.e., further cuts for positions and beds,
      including for maxillofacial clinics. While the professional and political
      concerns of the clinic doctors increase, health insurances are increasingly
      exerting influence on medical services and the financing of hospitals. This can
      prove life threatening for the clinics. The administrative structure of the
      clinics is also being questioned and is to be replaced by a collegial system. But
      the survival of the clinics and their personnel structure depend specifically on
      qualified management, clearly set goals, the ability to integrate, and openness
      to innovation. The advanced education of young oral and maxillary facial surgeons
      should be reconsidered, and more unlimited positions for medical specialists
      should be created. If the high standard of our specialty and the quality of
      education can be strengthened and extended, the perspectives for the future of
      clinical oral and maxillofacial surgery can be considered to be propitious, in
      spite of aggravated conditions.

PMID- 10938643
TI  - [Primary surgical treatment of lip-jaw-palate clefts in the year 2000. Report of
      the development of methods in the last 30 years and current status of surgical
      technique].
AB  - In this paper an attempt is made to survey the surgical treatment of cleft lip
      and palate regarding all classifications and all parts of the cleft. The most
      important developments up to 30 years ago to have been summarized in Millard's
      three-volume "Cleft Craft". Therefore, the author tries to analyze the present
      state-of-the-art cleft surgery. This part is certainly of a subjective nature due
      to the high rate of complexity in cleft malformations.

PMID- 10938644
TI  - [Secondary operations in lip-jaw-palate clefts].
AB  - In spite of all interdisciplinary efforts and functionally oriented operation
      procedures, there are still unsatisfying results in the treatment of cleft lip
      and palate (CLP) patients. Secondary corrections involve upper lip, nose, and
      palate (fissures). In some cases, it is necessary to reposition the complete
      maxilla. Finally, there are indications for speech improving measures and total
      septorhinoplasties. Dental treatment can be brought to a positive end by means of
      implant-borne prosthodontic work. In this paper, some of the anatomical and
      physiologic conditions and surgical procedures are described, which may serve as
      a basis for a functionally orientated treatment of sequelae after primary CLP
      care.

PMID- 10938645
TI  - [Craniofacial abnormalities].
AB  - Most craniofacial malformations result from a premature fusion of skull sutures.
      Depending on the scope of the sutures affected, the results are more or less
      distinct deformations of the facial and cranial skull with substantial negative
      effects on functional as well as esthetic aspects. The etiopathology is still
      unclear. Various therapies have been developed over the past 100 years. However,
      Tessier's technique of fronto-orbital advancement has been an important milestone
      in the treatment of these malformations. Numerous adjustments have since
      perfected this operational technique. It is now possible to treat practically all
      skull malformations with the surgical techniques available today. At the same
      time, these techniques have also aided the advancements in tumor surgery and
      traumatology.

PMID- 10938646
TI  - [Vascular and neural malformations].
AB  - The presentation of vascular and neural malformations in an understandable
      terminology permits accurate diagnosis, proper treatment, individualized
      prognosis, and also stimulates studies of pathogenesis. The descriptive
      classification includes: NF 1 and NF 2; hemangiomas, low- and high-flow vascular
      malformations, combined malformations, and hypertrophy; and syndromes such as,
      Parkes Weber, Klippel-Trenaunay, Maffuci's, and multiple dysplasia syndromes.
      Lymphatic malformations are abnormalities of lymphatic development. The list of
      treatment includes surgical and nonsurgical treatment. Not all vascular
      malformations can be successfully treated. Coping with NF is a challenge for
      both, affected individuals and health care professionals. NF is often associated
      with a myriad of anomalies that present a lot of problems for plastic surgery. In
      certain cases watchful waiting seems justified but not in cases of severe
      problems, giant growth, and local complications.

PMID- 10938647
TI  - [The development of modern osteosynthesis].
AB  - Within the last 30 years, rigid fixation has revolutionized a wide range of
      treatment procedures in cranio-maxillofacial surgery. Rigid fixation allows for a
      three-dimensional reconstruction of the facial skeleton. In fracture treatment
      and following osteotomies in orthognathic surgery, any postoperative maxillo
      mandibular fixation by dental arch bars can be avoided. Rigid plate and screw
      fixation began in 1886 when the Hamburg surgeon Carl Hansmann presented his
      experiences with the plate and screw system, which he had developed. Besides
      fractures of the extremities, Hansmann also reported about two cases of mandible
      fractures he had treated. Thus, Hansmann is the first representative of rigid
      plate fixation in maxillofacial surgery. Because of the high rate of
      complications, plate and screw osteosynthesis was not generally accepted for a
      long time. This changed when the Belgian surgeon Robert Danis in 1949 introduced
      the principle of axial compression of the fracture ends. His idea of axial
      compression was picked up by the ASIF Swiss research group and was further
      developed for clinical application in trauma surgery of the long bones in the
      early 1960s. Because of anatomical reasons, appliances used by the ASIF in the
      surgery of extremities could not be used in maxillofacial surgery. Therefore, in
      1968, Luhr developed an automatic compression plate, which in a simple way
      realized the principle of axial compression. With this compression screw plate,
      Luhr performed, in 1967, the first compression plating in the maxillo-facial area
      in the world. Numerous publications by other authors about similar procedures
      followed. Different treatment principles using monocortical mini plates without
      axial compression for treatment of mandibular fractures and later also for
      fractures of the midface were introduced, namely, by Michelet and also by Champy.
      Based on the experiences of fracture treatment by plate and screw fixation,
      various systems for mandibular reconstruction following tumor resection or defect
      fractures were developed. With these reconstruction plates, a rigid alloplastic
      bridging of defects could be performed as well as rigid fixation of bone grafts
      using axial compression. The main advantage of these procedures was the avoidance
      of any postoperative MMF. Rigid fixation has also revolutionized orthognathic
      surgery. The avoidance of any MMF following osteotomies of the facial skeleton
      was the main advantage. The introduction of implant materials, which are highly
      resistant to corrosion (vitallium, titanium), and the development of plating
      systems of adequate dimensions for use within different areas of the complex
      facial skeleton has led to a high degree of perfection of rigid fixation in
      cranio-maxillofacial surgery.

PMID- 10938648
TI  - [Resorbable polymers as osteosynthesis material].
AB  - The use of resorbable osteosynthesis materials spares the need for metallic
      implants and second operative procedures, which are often necessary, to remove
      the material. Appropriate substances are polymers and copolymers of glycolic and
      lactic acid. In a literature review, material characteristics, their degradation,
      and applications in animal experiments and clinical studies are presented.
      Particularly, the possible reasons of foreign body reactions occurring during the
      degradation period and material-related difficulties in practical use are
      discussed. It is evident that the use of low crystalline or amorphous polymers
      with in vivo long-lasting strength offers a secure and uncomplicated healing of
      fractures. Therefore, in future these substances will be an interesting
      alternative to common metallic osteosynthesis materials.

PMID- 10938649
TI  - [Traumatology. Mandibular fractures excluding condylar fractures].
AB  - Functionally stable fixation via bicortical osteosynthesis on the one hand, and
      monocortical non-compression osteosynthesis on the other, are still two competing
      concepts in treating mandibular fractures. A survey of the literature shows that
      complicated fractures with severe dislocation of the fragments have the lowest
      rate of complications after functionally stable fixation, whereas non-complicated
      fractures without significant dislocation in the distal part of the mandible can
      be treated successfully via monocortical non-compressive osteosynthesis as well.
      It seems that pre- and intraoperative parameters can be helpful in describing the
      character of a mandibular fracture in order to give a differential indication
      between the two therapeutical concepts. The consideration of only seven
      parameters, as the mandibular fracture score does, provides many combinations of
      describing a fracture, so that former studies with their small number of patients
      make only a rather inaccurate differential indication possible. As long as there
      is no prospective multi-center study giving a guideline to classify mandibular
      fractures, the rigid internal fixation via functionally stable osteosynthesis
      should be preferred in all cases which are not "clear, easy to handle" fractures.

PMID- 10938650
TI  - [Fractures of the mandibular condyle].
AB  - Among mandibular fractures, those of the condylar neck hold a special position
      due to the exceptional anatomical situation. Computer assisted tomography and
      magnetic resonance tomography have improved diagnostic evaluation. Indication for
      surgical treatment is given in cases of severely displaced or dislocated
      fractures. In surgical management, the preauricular, submandibular,
      retromandibular, and oral approach have been established. For sufficient fixation
      of fragments, procedures rendering a functional stability, like osteosynthesis
      with lag screw or by miniplating, are required.

PMID- 10938652
TI  - [Burns].
AB  - The therapy for burn injuries has established a definable management: percentage
      of the body surface area burned and thickness are important for the method of
      treatment (ambulant, on ward, intensive burn center). Open and close wound care
      with different bandages, in combination with primary surgery, has increased the
      probability of survival. A special problem is the aesthetics and function of the
      head and neck area. Hypertrophy and keloid scars may be disturbing, especially in
      children who have had a scald accident (41.2% of cases were children up to 5
      years of age). The possibilities of correction are multiple: conservative therapy
      (bandages, ointment treatment, physical therapy) or surgical intervention with
      free skin transplantation or difficult flaps (pedicle flap, free graft, expanded
      flap, and microvascular anastomosed flap). The aim of research is also to cover
      large defects with skin culture from small donor areas. It is necessary to
      establish maxillofacial and plastic surgery from the beginning of the treatment
      for aesthetic and functionally acceptable results.

PMID- 10938653
TI  - [Gunshot injuries].
AB  - Gunshot wounds result in a great amount of tissue damage, relating almost always
      to fractures and defects of the skeleton. The damage varies in relation to the
      speed, size, shape, and striking angle of the projectile and to the disruption of
      hard tissue fragments, which multiply the tissue laceration acting as secondary
      missiles. The rules to be observed in treatment of gunshot wounds are based on
      experience which was gained during World War I and II. Most of the rules have
      proved to be a success and may be summarized as follows: approach from inside to
      outside, preservation of the anatomical relationships of the remaining bony
      tissues, and primary wound closure. On the other hand, considerable progress has
      been made concerning reconstruction and establishing a number of new methods in
      order to create better functional and esthetic results.

PMID- 10938651
TI  - [Management of mid-facial fractures].
AB  - In the past, treatment of maxillofacial fractures was characterized by low
      incidences of midface fractures, while severe cases were associated with a high
      death rate. Over the last decades the application of new techniques has provided
      a successful outcome in the management of these more frequently observed
      injuries. With the introduction of antibiotics and the principles of modern
      anesthesiology, conservative methods of fracture treatment such as intermaxillary
      fixation and the application of extension devices were increasingly replaced by
      surgical techniques. The development of different osteosynthesis plate and screw
      systems in the early 1970s has made three-dimensional reconstruction a standard
      of care in the surgical treatment of midface fractures. With the recent
      introduction of commercially available bioresorbable systems, removal of
      osteosynthesis material has become an unnecessary procedure. Further research in
      innovative techniques of maxillofacial surgery and imaging, such as image-guided
      surgery by computer navigation, may be warranted to minimize surgical approaches
      and decrease incidences of perioperative morbidity.

PMID- 10938654
TI  - [Tumor surgery].
AB  - Surgery is still the primary therapeutic approach in treatment of tumors in the
      head and neck area, dating back to the early nineteenth century. More than 150
      years ago, hemimaxillectomies and mandibular resections as well as
      hemiglossectomies were already performed by leading surgeons. The block principle
      we are now following dates back to Crile, who also established the principle of
      cervical lymph node dissection. Ablative oncologic surgery has always been
      closely linked with plastic and reconstructive surgery, rendering radical
      surgical interventions possible without disfiguring patients. The development of
      facial reconstructive surgery proceeded in stages, in the first instance as
      secondary reconstruction using tube pedicled flaps. The change to the concept of
      primary reconstruction occurred via arterialized skin flaps and myocutaneous
      flaps to the widely accepted and performed free tissue transfer. Free bone
      grafting, inaugurated earlier and still representing the majority of bone
      grafting, has been supplemented for certain reconstructive purposes by free
      vascularized bone transfer from various donor sites. Although the five-year
      survival rate of carcinoma of the oral cavity has remained unchanged in the past
      30 years, distinctive improvements in tumor surgery can be recorded. This is
      primarily based on improved diagnostics such as modern imaging techniques and the
      refinement of surgical techniques. The DOSAK has worked out distinctive
      guidelines for effective ablative oncologic surgery. Surgical approaches offering
      wide exposure and carrying low morbidity play a decisive role in radical
      resections. For this reason, midfacial degloving offers an essential improvement
      for the resection of midface tumors, especially from an aesthetic point of view.
      Tumors situated deep behind the viscerocranium at the skull base can be clearly
      exposed either through a lateral approach following a temporary osteotomy of the
      mandibular ramus or a transmandibular, transmaxillar, or transfacial approach
      with minimal morbidity. Concerning the concept of neck dissection, radical
      techniques are more and more abandoned in favor of a more conservative procedure.
      Actual inquiries concerning present surgical procedures as to the surgical
      strategy in "N(o)-neck" or marginal and segmental resection in mandibular
      adherent carcinomas demand scientific clarification.

PMID- 10938655
TI  - [Chemotherapy and radiochemotherapy in tumors of the head-neck area].
AB  - Standard curative therapy in head and neck cancer, especially in oral cavity
      carcinoma, consists, so far, of surgery. Until today, chemotherapy using standard
      drugs has failed to be effective beyond controlling cancer manifestations and
      palliation of symptoms. The introduction of chemotherapy and radiotherapy as
      adjuvant treatment, however, may improve overall survival and curative options. A
      multicentric randomized trial, initiated by DOSAK, has compared results after
      radical surgery alone with results of combined preoperative radio-chemotherapy
      followed by radical surgery. The life table analysis substantiated improved
      survival rates in the group of patients whose treatment included chemotherapy and
      radiation.

PMID- 10938656
TI  - [Current status and prospects of chemoprevention in oral squamous epithelial
      carcinomas and precancerous lesions].
AB  - Second primary tumors in initially cured patients remain the greatest challenge
      in therapy for oral squamous cell carcinomas. The concept of field concerization
      is the most accepted hypothesis for the cellular and subcellular damages
      resulting in neoplastic transformation in the upper aerodigestive tract by risk
      factors such as chronic alcohol and tobacco abuse. Recent studies investigated
      several agents and regimens with benefit for chemoprevention of oral squamous
      cell carcinomas. In our review, the results of the most promising agents were
      studied. Despite discouraging results from recent intervention trials, studies in
      oral squamous cell carcinomas reported response rates up to 92%. In our
      investigation, two groups of patients were treated daily with 100 mg alpha
      tocopherol, 75 mg beta-carotene, and 1000 mg ascorbic acid per os. The first
      group consisted of 24 patients with leukoplakia of the oral cavity. The second
      group included 24 patients with premalignant lesions after R0-resection of
      primary oral squamous cell carcinoma. Biopsies were taken from both groups prior
      to therapy and after 12 weeks follow-up. Flow cytometry analyses were performed
      and nucleolar organizing regions (NOR) were examined. An overall histological
      response rate of nearly 98% was noticed. Additionally, the pretherapeutic regimen
      increased cell kinetic parameters, such as the S-phase portion, and the average
      number of NOR per cell nucleus decreased. These results indicate that the chosen
      combination has substantial activity in oral premalignant lesions. Nevertheless,
      basic research is required in investigating valid biomarkers for chemoprevention
      studies.

PMID- 10938657
TI  - [Basaliomas].
AB  - Basal cell carcinoma is the most frequent skin tumor in humans. It is mostly
      located in the face and its incidence is steadily rising. The tumor develops from
      basal, undifferentiated epithelial cells of the skin and its appendices and shows
      locally destroying growth, but generally without metastatic outspread typical of
      carcinomas of other origin. The tumor does not occur on the vermilion border of
      the lips and in the mucosa. Surgery is the most widespread and accepted treatment
      of basaliomas. It gives the possibility of histologic diagnosis of the whole
      specimen including margins of resection and allows immediate closure of the
      defect by means of plastic surgical methods. Regarding aesthetic and functional
      demands of the region, maxillofacial surgeons have the best prerequisites for
      this treatment. Recent research results clearly demonstrate the role of UVB light
      in the etiology, which is modified or promoted by genetic factors. Because of its
      typical malignant properties, such as progressive growth and infiltration, the
      term "basalioma", which is mostly used in German, should be replaced by "basal
      cell carcinoma" as it is known in the international literature.

PMID- 10938658
TI  - [Malignant melanoma in the area of the head and neck].
AB  - Malignant melanoma is one of the most frequent malignancies of the skin. This is
      particularly true of malignant melanoma in juveniles. Its incidence has more than
      doubled from the 1970s to the mid-1990s. Presently, 15 new cases are recorded per
      100,000 inhabitants a year in Germany. At Fachklinik Hornheide, a tumor center
      specializing in skin neoplasm with patients being referred from all over Germany,
      the number of melanoma patients treated per year has been approximately 500-550
      for the past 10 years. In the present study, the state-of-the-art therapy for
      primary melanoma and treatment of the regional lymph node system is discussed.
      The radical treatment formerly advocated with wide tumor resection plus radical
      neck dissection is no longer justified for this immunogenic malignant tumor
      caused by endogenic as well as exogenic factors. "Sentinel lymph node" imaging by
      means of radioactive substances for diagnosing possible melanoma metastases in
      adjacent lymph nodes has changed the therapeutical concept. Tumor staging by
      means of ultrasound, CT, MRT, or PET allows the differentiation of tumors without
      distant metastases and a favorable prognosis, from melanomas which have to be
      considered as generalized disease. In addition to surgical resection of the tumor
      and neck dissection for removal of lymph nodes, adjuvant immunotherapy with
      interferon-alpha is capable of prolonging survival without a recurrence.
      Palliative chemotherapy or immunotherapy are valuable options for cases with
      generalized melanoma. Vaccination with a melanoma-associated antigen or dendritic
      cells is at an experimental stage and may become part of future treatment
      strategies.

PMID- 10938659
TI  - [Odontogenic tumors].
AB  - The clinical symptoms of odontogenic tumors are non-specific. On the
      roentgenographs one most often sees radiolucencies within the bone, sometimes in
      combination with scattered or diffuse radioopacities. Root resorptions may be
      another important feature. After a short historical introduction on the
      development of today's classification of odontogenic tumors (WHO), each
      individual type of neoplasm is discussed briefly. Out of this, a therapeutic
      regime is developed that places each of the 22 entities into one of the following
      four groups: malignant, locally aggressive, tumors with recurrences, and non
      recurrent ones.

PMID- 10938660
TI  - [Bone tumors and tumor-like lesions of the jaw. Findings from the Basel DOSAK
      reference registry].
AB  - Within this chapter, tumors which produce bone matrix (osteoid) or other bone
      forming tissues, like cartilage, connective tissue, and cementum or originate
      within the bone marrow are described. In addition, those lesions are mentioned
      which, according to the WHO, are typical for the jawbones and are therefore
      included within the 1992 WHO classification of odontogenic tumors. Vascular and
      epithelial tumors which may also be observed in the jaws are not described. All
      the lesions and tumors reported have in common a more or less similar clinical
      and radiological appearance. A precise diagnosis, therefore, can only be
      established by a sufficient biopsy which should be seen by a pathologist with
      experience in this field. In addition to clinical, radiological, and histological
      appearances, therapeutic necessities are described. The data from recent
      publications are taken into account. This presentation is based on the data
      collected within the reference registry of the German-Austrian-Swiss Study Group
      of Tumors of the Face and Jaws (DOSAK) in Basel.

PMID- 10938661
TI  - [Therapeutic facial surgery possibilities for orbital tumors].
AB  - Based on a large experience of more than 400 orbital tumours which were treated
      operatively, the surgical strategies are described in detail. A surgical approach
      including the temporary removal of one or more bony orbital walls provided
      excellent exposure of the intraorbital structures. Using microsurgical techniques
      for tumour removal the surgical morbidity could be minimized. Subsequent
      refixation of the osteotomized orbital bones with microplates and screws and skin
      incisions within the hair bearing parts of the skull resulted in excellent
      postoperative function and cosmesis. For many malignant orbital tumours
      definitive cure can only be achieved by an orbital exenteration procedure. An
      individually tailored surgical and reconstructive strategy (if possible
      preservation of eyelid skin, tarsal and bulbar conjunctiva) gives a significant
      benefit, as well with respect to function as to the esthetic outcome of the
      patient.

PMID- 10938662
TI  - [Results of the DOSAK tumor register].
AB  - The German-Swiss-Austrian Group on Maxillofacial Tumors (DOSAK) has been
      performing observational studies in oral cancer. Since 1989, approximately 1600
      cases of tumor of the head and neck per years has been collected in a central
      tumor registry. The database consists of more than 16,000 patients from 71
      clinics; almost two-thirds are primary cases of squamous cell carcinoma. The data
      show great differences in patho-anatomical findings, therapy concepts, and five
      year survival rates among the hospitals.

PMID- 10938663
TI  - [Distraction in mouth, jaw and facial surgery].
AB  - Distraction osteogenesis is established worldwide as a new surgical technique.
      The former rule, not to osteotomize before the end of bone growth, is no longer
      valid. Today, distraction starts as early as infancy as well as in childhood and
      adolescence. This new method allows the gain of bone in the distraction gap so
      that bone grafting can be avoided. Distraction is indicated in hemifacial
      microsomias, multiple syndromes with mandibular malformations, mandibular
      retrognathia, posttraumatic jaw deficiencies, craniofacial malformations,
      alveolar ridge resorptions, and alveolar ridge resections. Distraction surgery
      started in the mandible and was continued in the maxilla and the craniofacial
      region. Alveolar ridge distraction followed. After using extraoral devices, the
      development of internal applicable distractors followed. Today, bi- or
      tridirectional internal devices are already available. The whole treatment
      concept includes the orthodontist. Distraction planning before surgery is of
      great importance. The literature presently includes methods, indications, and
      case reports but only few results, which we compare with our experiences.

PMID- 10938664
TI  - [Orthognathic surgery: corrective bone operations].
AB  - The article reviews the history of orthognathic surgery from the middle of the
      last century up to the present. Initially, mandibular osteotomies were only
      performed in cases of severe malformations. But during the last century a precise
      and standardized procedure for correction of the mandible was established.
      Multiple modifications allowed control of small fragments, functionally stable
      osteosynthesis, and finally a precise positioning of the condyle. In 1955
      Obwegeser and Trauner introduced the sagittal split osteotomy by an intraoral
      approach. It was the final breakthrough for orthognathic surgery as a standard
      treatment for corrections of the mandible. Surgery of the maxilla dates back to
      the nineteenth century. B. von Langenbeck from Berlin is said to have performed
      the first Le Fort I osteotomy in 1859. After minor changes, Wassmund corrected a
      posttraumatic malocclusion by a Le Fort I osteotomy in 1927. But it was Axhausen
      who risked the total mobilization of the maxilla in 1934. By additional
      modifications and further refinements, Obwegeser paved the way for this approach
      to become a standard procedure in maxillofacial surgery. Tessier mobilized the
      whole midface by a Le Fort III osteotomy and showed new perspectives in the
      correction of severe malformations of the facial bones, creating the basis of
      modern craniofacial surgery. While the last 150 years were distinguished by the
      creation and standardization of surgical methods, the present focus lies on
      precise treatment planning and the consideration of functional aspects of the
      whole stomatognathic system. To date, 3D visualization by CT scans,
      stereolithographic models, and computer-aided treatment planning and simulation
      allow surgery of complex cases and accurate predictions of soft tissue changes.

PMID- 10938665
TI  - [Implantology].
AB  - Endosseous osseointegrated implants have become an integral part of the treatment
      scheme for the prosthetic reconstruction and rehabilitation of masticatory
      function following scientific studies of the reactions between implant and soft
      and hard tissues. Furthermore, implants offer good chances for prosthetic
      rehabilitation in the insufficient bone site, if the extremely atrophic jaw is to
      be reconstructed by grafting procedures with avascular and vascular grafts, by
      guided bone regeneration, by distraction osteogenesis, by bone substitutes and in
      the future by osteoinductive proteins in order to prepare the conditions for
      implant insertion. Those reconstruction procedures combined with implants become
      often necessary, if complicated hard and soft tissue defects of the skull have to
      be reconstructed to create the prerequisites for the stabilisation of epitheses
      or to insert implant-supported devices.

PMID- 10938666
TI  - [Preprosthetic surgery (without implantology)].
AB  - This paper describes preprosthetic surgery from its historical beginnings to its
      present state-of-the-art status. Future perspectives of preprosthetic surgery are
      also outlined, excluding implants. In an enquiry of 250 German-speaking
      maxillofacial departments, 160 responded. Results showed that a surprising 30-50%
      of the institutions are still following guidelines for procedures which have been
      proven by scientific follow-up studies to be almost 100% unsuccessful.

PMID- 10938667
TI  - [Dento-alveolar surgery].
AB  - The first publications in dentoalveolar surgery date back to the eighteenth
      century, while basic works in German-speaking areas appeared in the first half of
      the 20th century. Dentoalveolar surgical issues are still present within
      craniomaxillofacial surgery nowadays. Nomenclature has changed little while
      contents in certain areas shift away from surgical practical aspects towards
      biological-medical points of view. The new technologies of dentoalveolar surgery
      are being developed for maximal patient safety using minimal invasive methods.
      Other, traditionally non-surgical, dental subspecialities are taking over
      dentoalveolar surgical issues. Oral surgery remains a part of craniomaxillofacial
      surgery and should continue to get a major boost from it in the future.

PMID- 10938669
TI  - [Microsurgical soft tissue transplantation].
AB  - Since the first microsurgical transplantation in 1971, numerous tissue regions
      which are appropriate for transplantation have been researched. In particular,
      cutaneous or fasciocutaneous and musculocutaneous, as well as jejunum and fat
      tissue transplants are involved. In maxillofacial surgery, predominantly radial
      underarm flaps and scapular or parascapular flaps are used. The indications for
      both kinds of flaps range from intraoral defects, including tongue defects, and
      defects after maxillary resection, to defects following tumor resection of the
      face. In the framework of radical tumor surgery involving regional lymph drainage
      ducts, the musculus latissimus dorsi flaps and the musculus rectus abdominis
      flaps are indicated for the covering of deep-reaching defects. Jejunum
      transplants are appropriate mainly in the region of the soft palate and
      pharyngeal walls. Free microsurgical fat tissue transplants are indicated for
      extensive subcutaneous defects. The technique of lifting transplants and
      transferring them is so refined that results are comparable to those attained by
      using conventional flaps.

PMID- 10938668
TI  - [Roentgen diagnosis in oromaxillofacial surgery].
AB  - A vital X-ray imaging technique in oral and craniomaxillofacial surgery is the
      panoramic X-ray. Due to its variety of special projections, including imaging of
      the transversal level and low exposure to radiation, it is suitable for answering
      many clinical questions and for diagnostics of various findings. It has become
      possible to minimize the necessary doses by further development of technology and
      devices, as well as of X-ray films and by new detection systems, such as sensors
      or screens. In some clinical cases, the diagnostic deficiencies of conventional
      imaging techniques make computed tomography (CT) and magnetic resonance (MR)
      imaging indispensable. Although MR is particularly suitable for soft tissue
      imaging, it has also become helpful in finding cortical changes by shorter
      measuring times. In certain cases, e.g., changes to bone metabolism,
      differentiated methods of nuclear medicine make image-aided analysis of function
      possible.

PMID- 10938670
TI  - [Flap-plasty of the face].
AB  - While facial and craniofacial deformities and facial trauma comprise considerable
      amounts of bony surgery, the treatment of facial skin tumours requires
      essentially different approaches and skills of soft tissue surgery of the
      surface. Although the specialty of maxillofacial surgery developed during the
      World Wars in Europe, soft tissue reconstruction of the face has been greatly
      refined since then. A table of ten reconstructive principles is further
      elucidated in the text followed by 17 clinical examples, from the scalp to
      various areas of the face to the lips. As aesthetics play a dominant role in
      facial reconstruction, local flaps are the first choice, while pedicled flaps
      from the chest or microvascular free flaps are only considered for otherwise too
      large defects. Only very few exceptions exist to this rule. Facial skin tumours
      show a great variety of size and localization and resulting excisional defects
      may confront the surgeon with individual problems. Only when we master a great
      variety of reconstructive methods for all such sizes and combinations of defects
      can we excise malignant tumours with sufficiently wide, clear margins without
      hesitations or compromise.

PMID- 10938671
TI  - [Pedicled musculocutaneous and fasciocutaneous flap].
AB  - Pedicled musculocutaneous and fasciocutaneous flaps are still a prerequisite of
      reconstructive surgery. Although microvascular free flap transfer today plays a
      major role in modern one-step reconstruction concepts, the surgeon should be
      familiar with the anatomy and techniques of pedicled flaps. In the head and neck
      region especially, pedicled flaps from the pectoralis major and the latissimus
      dorsi muscle are of clinical importance. A major advantage of these flaps is in
      their simple and standardized surgical technique, which requires no further
      surgical qualification compared to microvascular transfer. The flaps are reliable
      and safe. They have a high degree of resistance against infection and therefore
      can be used in compromised tissues, which are frequently found in irradiated
      patients. The disadvantages are a reduced mobility regarding the arch of
      rotation. Pedicled fasciocutaneous flaps have no importance in reconstructive
      surgery of the head and neck region.

PMID- 10938672
TI  - [Eyelid replacement-plasty].
AB  - After a short description of the history of eyelid reconstruction, the causes of
      defects are discussed. For the primary and secondary treatment of thermic
      injuries, a full-skin graft is recommended and the indication of combined skin
      cartilage transplants is mentioned. For deep defects, numerous methods of eyelid
      reconstruction are available. The differentiated indication for manifold initial
      situations is discussed in detail. The most important techniques are described on
      the basis of various examples.

PMID- 10938673
TI  - [Split skin and full-thickness skin grafts].
AB  - Skin grafting is one of the earliest described surgical procedures. In the age of
      microsurgery and free-tissue transfer, it remains a utilitarian means of
      achieving soft tissue reconstruction. Free skin grafts can be classified into
      three types: full-thickness skin grafts, split-thickness skin grafts, and
      composite grafts. The indications, techniques, donor site considerations,
      postoperative complications, and results of each type are reviewed. The full
      thickness skin graft for facial and cervical reconstruction is usually harvested
      from the upper arm or postauricular region and is applied under a tie-over
      dressing. When comparing the functional and aesthetic results of full-thickness
      skin grafts and split-thickness skin grafts in terms of morbidity, skin
      elasticity, skin sensitivity, matching, and scar recurrence, full-thickness skin
      grafting seems to be the most adequate technique.

PMID- 10938675
TI  - [Microneurosurgery].
AB  - Micronervereconstruction of motor and sensitive nerves in the head and neck area
      today has an established range of indications. Surgical procedures of external
      and internal neurolyses, nerve coaptation and nerve transplantation techniques
      are well standardized. With microneurosurgery of motor nerves, satisfying or good
      results can be generally obtained. Success rates exceeding 50% following
      sensitive nerve reconstructions justify the performance of the procedures, more
      so because of the subjective improvements for the individual patient.
      Perspectives can be seen in further simplification of surgical methods of
      harvesting nerve grafts, e.g., by development of minimally invasive, eventually
      endoscopically guided procedures. Allogenic nerve grafts may also be applied.
      Initial experiments with nerve distractions are encouraging. A better
      understanding of nerve lesions on cellular and molecular biological levels may
      improve our knowledge of posttraumatic regulatory procedures and may lead to
      future possibilities of nonsurgical treatment options for peripheral and central
      nerve lesions by guided regeneration.

PMID- 10938676
TI  - [Esthetic facial surgery].
AB  - In the last few years, aesthetic facial surgery--especially soft-tissue surgery-
      has received increasing attention, not only from the medical profession but also
      particularly from the media. This is due, in part, to the growing level of
      general acceptance of the formerly stigmatized issue of aesthetic surgery, and in
      part to increasing patient expectations. Moreover, the introduction of less
      invasive procedures with outstanding long-term results have brought about a
      considerable change in aesthetic surgery. A comprehensive account of face
      lifting, forehead lifting, brow lifting, blepharoplasty, cervical liposuction and
      adjuvant techniques of skin rejuvenation will be given and discussed.

PMID- 10938674
TI  - [Microsurgical bone replacement].
AB  - Microvascular bone transplantation has become a routine procedure. The iliac
      crest, scapula, and fibula are the most common donor sites. These are used for
      reconstruction of tumor-related defects or after osteoradionecrosis. But
      additional indications have been developed as defects after trauma, extreme
      atrophy, or hemifacial microsomia. In the future, three-dimensional techniques
      will improve transplantation surgery and will enable the prefabrication of
      transplants.

PMID- 10938677
TI  - [Methods of pain therapy in mouth, jaw and facial surgery].
AB  - Pain therapy in the oral and maxillofacial region is still a problem. Before
      starting therapy, the genesis of pain has to be carefully clarified. The article
      presents the most important syndromes, aspects concerning diagnosis and
      differential diagnosis as well as therapeutic schemata.

PMID- 10938678
TI  - [Robotics].
AB  - Content of this paper is the current state of the art of robots in surgery and
      the ongoing work on the field of surgical robotics at the Clinic for
      Maxillofacial Surgery at the Charite. Robots in surgery allows the surgeon to
      transform the accuracy of the imaging systems directly during the intervention
      and to plan an intervention beforehand. In this paper firstly the state of the
      art is described. Subsequently the scientific work at the clinic is described in
      detail. The paper closes with a outlook for future applications of robotics
      systems in maxillofacial surgery.

PMID- 10938679
TI  - [Telenavigation and expert consultation using a stereotaxic surgical
      videoserver].
AB  - The exponential increase of medical information creates a need for new methods in
      the visualization of medical imaging modalities for diagnosis and therapy. In
      this sense, visualization includes the display of medical image data and image
      guided stereotaxic navigation as well as the advice of an expert. The Artma
      Virtual Patient System enables a remote expert to observe the surgical procedure
      via the Internet and interactively modify the interoperative visualization from
      the remote location. The expert in the remote location receives the planning data
      almost in real time over TCP/IP from a stereotaxic videoserver. In addition to
      live video streaming, stereotaxic navigation data are sent over the network as
      rigid body coordinates. The expert modifies the surgical simulation on the remote
      computer and the modified operating plan is sent back to the operating site. By
      teleconsulting, the composite images and overlapping graphics--instruments,
      target structures, landmarks, contour--can be seen in affiliated clinics with the
      possibility of interactive graphical assistance. With this image fusion
      technology the knowledge of a remote expert is included in virtual data
      structures and visualized by the overlay with live video data (augmented reality)
      in real time during surgery.

PMID- 10938680
TI  - [Ultrasound in oromaxillofacial surgery].
AB  - Ultrasonography has gained acceptance in maxillofacial surgery as a first-choice
      diagnostic tool in soft tissue masses of the head and neck. To date, A-mode
      sonography of the maxillary sinus is only performed in children and pregnant
      women. However, B-mode sonography is primarily performed in the assessment of all
      cervical lymph nodes because of its superior sensitivity in comparison to CT and
      MR, as well as in diseases of the salivary glands, solid tumors, and monitoring
      of distraction osteogenesis of the mandible. With color-coded ultrasonography as
      a combination of B-mode and blood flow information, vessels of the head and neck
      area or of planned flaps can be examined in a noninvasive manner. This is
      especially important in secondary microsurgical reconstructions. Moreover, the
      blood flow in any soft tissue masses can be evaluated. In spite of all texture
      and image analysis techniques, positive and negative lymph nodes cannot be
      differentiated in a safe manner. Three-dimensional sonography, e.g., panoramic
      pictures, and contrast enhancement are new technologies that will improve
      diagnostic accuracy of head and neck ultrasonography.

PMID- 10938681
TI  - [Bone substitutes].
AB  - The application of autogenous bone transplants is still the gold standard for all
      reconstructive surgery. The wish of surgeons for alternatives to autogenous bone
      grafts is reflected in the development of a variety of bone graft substitutes of
      synthetic or biological origin. The following review article is meant to provide
      the reader with a critical overview of all the alternative materials. In
      addition, we want to point to the tremendous progress made on this subject, made
      possible by the joint effort of surgeons and basic researchers. The results of
      this collaboration show that in the near future a new gold standard for
      successful reconstructive surgery will emerge and replace the use of autogenous
      bone transplants.

PMID- 10938682
TI  - [Conservative and surgical treatment possibilities in temporomandibular joint
      diseases].
AB  - For the most frequent TMJ derangements, highly efficient nonsurgical treatment is
      preferable. Within this concept, the interdependence between the TMJ and the jaw
      musculature is increasingly focussed. Surgical therapy is only an option under
      defined circumstances in cases resistant to nonsurgical treatment, or if
      nonsurgical treatment is meaningless from the beginning. Within surgical
      concepts, arthroscopy is becoming increasingly important. A close
      interdisciplinary cooperation between the dentist and oral and maxillofacial
      surgeon seems to improve the potential outcome in these cases.

PMID- 10938683
TI  - [Salivary gland diseases].
AB  - After more than 25 years of activity in the field of salivary gland surgery,
      especially parotid gland surgery, the following statements can be made. 1.
      Salivary gland diseases are extremely variable and their treatment requires vast
      clinical experience. 2. The judgement of salivary gland diseases requires highly
      competent pathologic assistance and a specialized laboratory in this respect. In
      the field of salivary gland pathology--like in many other specialized
      subdivisions in pathology--the need of a second opinion in order to increase the
      reliability of the original diagnosis has to be claimed once more. 3. A certain
      change has taken place in the diagnostic means. Modern techniques of
      visualization show a shift toward noninvasive sonography, but also toward
      computed tomography with or without contrast agents, and there is a steadily
      increasing shift toward magnetic resonance tomography as well. 4. The literature
      about salivary gland diseases and their therapy can no longer be overlooked and
      is unfortunately characterized by very different aspects of judgement, which in
      many cases hardly allow a comparative discussion of certain clinical and
      therapeutic questions. 5. Parotid gland surgery requires a clear concept
      concerning the different diseases, especially of the different oncologic
      entities. Surgical preparation of the facial nerve has to be mastered equally
      from the central and the peripheral course of the nerve.

PMID- 10938684
TI  - [Ethical approach to informed consent for participation in clinical studies in
      acute cerebral infarct].
AB  - OBJECTIVE: We sought to evaluate the application of the French law for the
      protection of persons participating in research studies in biology and medicine.
      Specifically, we examined comprehension and consequences of informed consent
      procedures in the field of stroke, characterized by an emergency setting,
      cognitive impairment and poor prognosis. PATIENTS AND METHODS: Patients (or
      proxies) included in recent years in clinical studies conducted in our Neurology
      Department for evaluating treatment of acute phase cerebral ischemia were
      interviewed to determine their knowledge of the disease, its treatment, the study
      protocol and the legal regulations, and the affective and psychological
      consequences of the informed consent procedure. RESULTS: Among 72 patients
      included in 7 studies ([fibrinolytic agent: 3 (n = 43), anticoagulant agent: 1 (n
      = 4), neuroprotective drugs (n = 25)], [7 randomized studies, 6 double-blind
      versus placebo, 5 with a 6-hour inclusion time interval]), 15 died during the
      acute phase, 5 were lost to follow-up, 4 refused to participate and 7 gave very
      partial answers. Consent was signed by the patient in 15% of cases, the spouse in
      50%, a descendant in 23%. These persons were aware of the spontaneous risk of
      death (85%) or definitive functional impairment (95%). Half of them thought a
      specific treatment existed, 11% had some idea of the mechanism of action of the
      proposed treatment while 67% learned about this mechanism from the information
      provided. Although they had received information, only 25% of the patients had
      knowledge of placebo and 7% of therapeutic risk. 37% expected complete recovery
      from the treatment, 44% partial recovery, and 13% were very disappointed by the
      outcome. 81% felt they were free to make their own decision. Although 86% did not
      know there was a law protecting them, 82% were in agreement with the requirement
      for their consent while 17% would have preferred to delay consent. Most wished to
      be given the opportunity to discuss the study again, after the acute phase, and
      to receive the results of the study. CONCLUSION: This study shows that most
      French stroke victims and their closest relatives are unaware of the law
      protecting persons in biomedical research and have poor knowledge of medical data
      after being given appropriate information. Even so, the quality of information
      increases the quality of the patient-physician relationship. Patients want to be
      free to make their own decision to consent to biomedical research, but their
      desire was more for good information than for the power to make their decision
      alone. Being asked to give informed consent in order to participate in a clinical
      study accentuates the affective and psychological consequences of stroke, a
      factor which should be taken into consideration during follow-up.

PMID- 10938685
TI  - [Acute acoustic trauma in military personnel. Evaluation of 1 year epidemiologic
      surveillance].
AB  - OBJECTIVES: Acute acoustic trauma (AAT) refers to damage to sensitive cochlear
      structures caused by excessive exposure to impulse noise. The aim of this study
      was to 1) assess the incidence of ATT in French soldiers and 2) to clarify the
      circumstances under which AAT occurs. PATIENTS AND METHODS: We carried out a
      prospective study of AAT events reported to medical officers in 1998. RESULTS:
      The incidence of AAT was 156 per 100,000 person-years (150-161). It was higher in
      conscripts and in soldiers aged under 31 years. Fifty-seven percent were wearing
      hearing protectors when the accident took place. CONCLUSION: According to these
      results, specific preventive programs were planned and should be assessed by
      epidemiological surveillance of exposed populations.

PMID- 10938686
TI  - [Iodine 131 uptake by a bronchogenic cyst in a patient with differentiated
      carcinoma of the thyroid gland].
AB  - BACKGROUND: After thyroidectomy for differentiated thyroid carcinoma,
      extracervical uptake of iodine 131 is suggestive of metastasic dissemination.
      False positives can however occur. CASE REPORT: Differentiated thyroid carcinoma
      was found in a female patient with a non-functional nodule. Two years after
      subtotal thyroidectomy and an ablative dose of iodine 131, the whole body scan
      showed abdominal mediastinal uptake with low serum thyroglobulin level.
      Considering the possibility of tumor recurrence or lymph node metastasis, the
      mass was excised. The histology diagnosis was mediastinal bronchogenic cyst.
      DISCUSSION: To date, iodine uptake in a bronchogenic cyst has not been reported
      among other false-positives previously described. The pathophysiology of this
      iodine 131 uptake in a bronchogenic cyst is still unknown: the presence of NIS
      symporter or a protein which can organify iodine in the mucus cells of the cyst
      remains to be proven.

PMID- 10938687
TI  - [Lung infection by Mycobacterium szulgai].
AB  - BACKGROUND: Mycobacterium szulgai is an uncommon atypical mycobacterium human
      pathogen. CASE REPORT: The clinical manifestations and radiographic findings in a
      31-year-old woman were strongly suggestive of pulmonary tuberculosis. The mode of
      transmission could not be determined. Mycobacterium szulgai was identified. The
      patient was treated with antituberculosis antibiotics and the clinical course was
      favorable. DISCUSSION: Mycobacterium szulgai is an atypical mycobacterrium
      difficult to identify. Its epidemiological features are unknown. This potential
      pulmonary pathogen is rarely described in the literature. Most cases have
      involved pulmonary, bone and joint or skin infections in immunodepressed
      patients. M. szulgai is relatively susceptible to classic antituberculosis
      antibiotics although standard regimens have not been established. Our patient
      required intensive care for mechanical ventilation.

PMID- 10938688
TI  - [Severe hypoglycemia and recurrence caused by disopyramide-clarithromycin
      interaction].

PMID- 10938689
TI  - [Duodenal diaphragm induced by aspirin].

PMID- 10938690
TI  - [MRI cholangiopancreatography in common bile duct pathology in a pregnant woman].

PMID- 10938691
TI  - [Genetic analysis after allograft: prudence!].

PMID- 10938694
TI  - [New blood transfusion partners in France].
AB  - The French Blood Agency, created in 1993, controls all aspects of the blood
      transfusion system. It is responsible for restructuring the blood transfusion
      system and for Good Manufacturing Practices. All incidences are reported to the
      blood monitoring system which also obtains further descriptions of such
      incidents. Blood transfusion policies have been modified to include monitoring of
      blood-associated morbidity. Successive reforms have led to the establishment of a
      new public system for blood transfusion. New structures and more formal
      designation of responsibilities are needed. The function of these new structures
      is to better control transfusion activities and prevent unknown risk.

PMID- 10938692
TI  - [Does dehydroepiandrosterone improve well-being?].

PMID- 10938695
TI  - [3rd European Congress of Chemotherapy (Madrid 7-11 May 2000). Resistance of
      bacteria to antibiotics: an ever increasing problem].

PMID- 10938693
TI  - [Doping: indispensible public education].

PMID- 10938696
TI  - [Doping: epidemiological studies].
AB  - PREVALENCE: Whatever method is used (observation, interviews, questionnaire,
      laboratory tests), it is difficult to collect epidemiological data on doping.
      Particularly difficult problems are related to the definitions of sports players
      and the drugs involved as well as the often illicit nature of drug use. RESULTS:
      The prevalence of doping in children and adolescents participating in sports is
      estimated at 3% to 5% with higher percentages in boys, older adolescents and
      those playing at a competition level. Use of anabolic steroids, as early as 8
      years of age, has increased since 1990, especially in girls. All studies have
      emphasized how easy it is for adolescents to procure any prohibited drug. In
      adults participating in amateur sports, the prevalence of doping would be 5% to
      15%. All sports are involved with higher prevalence in men, age ranges 20-25
      years and 35-39 years, and competitive level players. The main drugs used are
      stimulants, narcotics, corticosteroids and anabolic steroids. Combination of at
      least 2 drugs is frequent with an increase of mean daily dose over the last 15
      years. According to users, the drugs are obtained with a medical prescription, on
      the underground market, or from other participants. Few data are available on
      doping outside sports activities. In the French department Meurthe-et-Moselle,
      15% of the inhabitants use drugs to improve their occupational performance.
      CONCLUSIONS: Doping is more widespread than would be expected from antidoping
      control data. Other studies are needed to acquire more precise epidemiological
      data.

PMID- 10938697
TI  - [Effects of aging on kidney function and implications for medical practice].
AB  - PHYSIOLOGICAL AGING: Anatomical and physiological renal changes occur during
      normal aging in humans. These changes are different from the renal effects of
      many diseases frequently linked to aging and which require specific diagnosis,
      prevention and therapy. Renal aging varies from one patient to another or from
      one population to another. During common aging, anatomical changes are mild and
      physiological changes mainly affect glomerular filtration rate and water and salt
      metabolism regulation. IN THE ELDERLY: Glomerular filtration rate decreases
      slowly in healthy elderly people to reach 80 ml/mn at 80 years without any
      metabolic consequence. However, in old hospitalized patients, acute renal failure
      is frequent and occurs mainly during inflammatory or infectious disorders,
      dehydration or drug combinations enhancing regulation of glomerular filtration.
      Tubular function changes expose the elderly to increasing risk of dehydration
      which could be prevented in highly predictable situations such as
      gastrointestinal symptoms, poorly salted diets or anorexia. Estimation of the
      creatinine clearance is necessary whenever an acute medical events, mostly
      infectious diseases, occur in elderly people to adapt drugs doses to renal
      catabolism.

PMID- 10938699
TI  - [Milanese radiotherapy: Historical notes on great masters and a great school].

PMID- 10938698
TI  - [Optimal duration of anticoagulant treatment of venous thromboembolism].
AB  - RECURRENT THROMBOSIS VERSUS ANTICOAGULANT-RELATED BLEEDING: The optimal duration
      of anticoagulation for venous thromboembolism depends on the balance between the
      risk of thrombosis if anticoagulation is stopped, and the risk of bleeding if
      patients remain on treatment. In the past decade, five large well designed trials
      have been completed which have compared different durations of anticoagulation
      for the treatment of various categories of patients with venous thrombosis. In
      conjunction with the findings of a number of other prospective studies, these
      trials have helped to identify risk factors for recurrent venous thrombosis and
      anticoagulant-related bleeding, and have led to a better understanding of the
      optimal duration of therapy for individual patients. RISK OF RECURRENT
      THROMBOSIS: The risk of recurrent thrombosis is low if thrombosis was
      precipitated by a major reversible risk factor such as surgery. Patients with
      idiopathic thrombosis (no apparent risk factor) and those with persistent risk
      factors (e.g., cancer), have a high risk of recurrence. Some hereditary (e.g.,
      protein C, S or antithrombin deficiency) and acquired (e.g., antiphospholipid
      antibodies) thrombophilic states are risk factors for recurrence independently of
      whether thrombosis was, or was not, provoked by a major risk factor. DURATION OF
      THERAPY: Patients with a low risk of recurrence should be anticoagulated for
      three months. Others should be treated from 6 months to indefinitely, depending
      on the balance between the risk of recurrence and the risk of bleeding in each
      individual patient.

PMID- 10938700
TI  - [Images and words. Image transmission and reporting in thoracic radiology (II)].

PMID- 10938701
TI  - [Necrotizing fasciitis of soft tissues: role of diagnostic imaging and review of
      the literature].
AB  - PURPOSE: We retrospectively reviewed the diagnostic imaging findings
      (radiography, CT and US) of our cases of necrotizing fascitis of soft tissues
      looking for signs that could be useful for early and accurate diagnosis. MATERIAL
      AND METHODS: May 1991 to February 1998 we examined 130 patients with progressive
      necrotizing soft tissue infections; in 32 of them (22-84 years old) the
      retrospective pathologic diagnosis was necrotizing fascitis. Involved sites were
      the limbs (26/32), the cervical region (5/32) and the perineal region (1/32).
      Nineteen patients were submitted to conventional radiography, also for soft
      tissue studies. US was performed in an emergency setting in all the 32 cases, by
      a selected group of US operators particularly skilled in this kind of soft tissue
      condition. Contrast enhanced CT was performed in 9 cases. RESULTS: B-mode and
      Doppler US yielded useful and reliable information for prompt and correct
      diagnosis. Particularly these techniques showed changes in subcutaneous adipose
      tissue (28/32), fascia (18/32) and muscle (15/32). We found a good correlation
      between tissue changes as shown at US and histologic findings, but US missed
      changes in subcutaneous soft tissue and muscle in 11 cases (3/32 and 8/32,
      respectively) with subsequent histologic confirmation. Contrast enhanced CT
      better defined the extent of disease and possible complications, especially in
      sites that are difficult to study with US. DISCUSSION AND CONCLUSIONS: Early
      diagnosis and proper treatment are the key issues affecting the chances of
      recovery for patients with necrotizing fascitis. The clinical suspicion of this
      condition calls for prompt intervention with effective diagnostic protocols. B
      mode, and sometimes color Doppler, US and contrast enhanced CT, together with
      appropriate laboratory tests, can provide useful information for precise
      diagnosis and proper treatment.

PMID- 10938702
TI  - [Evaluation of the "N" factor in nonsmall cell lung cancer. Correlation between
      computerized tomography and pathologic anatomy].
AB  - PURPOSE: To evaluate the role of CT in identifying other morphological signs of
      metastatic lymph node involvement from non small cell bronchogenic carcinoma.
      This is done to improve N staging, a critical step in this disease. In fact,
      since diameter is the only criterion used to distinguish normal form abnormal
      lymph nodes, medistinal CT only has 80% diagnostic accuracy. MATERIAL AND
      METHODS: 137 patients with known or suspected lung cancer were examined with
      Helical CT during early and late arterial phases (2 min delay, 3 mm thickness, 5
      mm interslice gap) to depict node characteristics. Mediastinal lymph nodes,
      located according to the American Thoracic Society mapping, were considered
      normal when they were not visible or, if visible, less than 1 cm in diameter and
      of homogeneous density; lymph nodes over 1 cm in diameter and homogeneous density
      were considered reactive. A lymph node was considered metastatic when,
      independent of size, the following signs were found: central hypodensity;
      hyperdense thin/thick rim, with nodules within; hyperdense strands or diffuse
      hyperdensity in perinodal adipose tissue. The tumor site was also considered.
      RESULTS: Seventy patients were excluded because they were inoperable. Sixty-five
      of the remaining 67 patients were operated on, 1 underwent mediastinoscopy and
      another one mediastinoscopy followed by surgery. Based on the above CT signs, 46
      patients were staged as N0, 61 as N1 and 15 as N2. In 44/46 N0 patients there was
      agreement between anatomical and pathologic findings; 3 of the 44 patients had
      lymph nodes over 1 cm in diameter and with homogeneous density. Micrometastases
      to mediastinal lymph nodes (N2) were found at histology in 2/46 patients (CT
      false negatives). In the 6 N1 and the 15 N2 patients there was complete agreement
      between anatomical and pathologic findings; in particular, 9 N2 patients had
      lymph nodes less than 1 cm in diameter with signs of metastasis and 4 had lymph
      nodes over 1 cm in diameter with signs of metastasis and 2 had lymph nodes either
      over or less than 1 cm. In all N2 patients the tumor histotype and the
      mediastinal location were also considered relative to the lesion site.
      DISCUSSION: A closer correlation was found with node morphology and density than
      with size. Indeed, CT sensitivity, specificity and diagnostic accuracy were 97,
      100 and 97%, respectively, for the former versus 52, 93 and 77% for the latter.
      Adenocarcinoma was the predominant histotype (70.5%) in N2 patients. Metastases
      to node region 4 were predominant in right upper lobe carcinomas while node
      region 5 was predominant in left upper lobe lesions. CONCLUSIONS: Other criteria
      can be associated with size to improve CT diagnostic accuracy in N staging.
      Technique optimization plays a major role particularly in the late, thin slice,
      examination phase.

PMID- 10938703
TI  - [Anastomosis between the left internal spermatic and splanchnic veins.
      Retrospective analysis of 305 patients].
AB  - PURPOSE: To investigate the presence and the rate of anastomoses between the
      internal spermatic vein (ISP) and visceral veins in patients with idiopathic
      varicocele. MATERIAL AND METHODS: We retrospectively reviewed the venographic
      findings of 305 patients (age range 14-40 years; mean age 28 years) with a US
      diagnosis of varicocele who were submitted to sclerotherapy from 1991 to 1997.
      All the venographic examinations had been carried out with selective injection of
      the ISP for complete mapping of gonadal vessels. RESULTS: The most frequent
      venographic patterns (type I) was identified in 139/305 patients (45.5%), type
      III was found in 86/305 (28.2%), type V in 37/305 (12.1%). Type IVb was found in
      32 cases (10.4%) and type IVa in 9 (2.9%). Type II was seen in 2/305 patients
      only (0.6%). Single or double anastomoses between the ISP and portal or systemic
      veins were found in 34 patients (11.1%); a single or double communication with
      the left colic vein was observed in 24 cases (7.8%) and a communication with the
      paravertebral venous system in 10 patients (3.2%). Other anastomoses with the
      inferior mesenteric veins and splenic veins were seen in 7 and 4 patients (2.2%
      and 1.3%, respectively). DISCUSSION AND CONCLUSION: The presence of vascular
      variants and of communications of the ISP with the visceral veins needs accurate
      venographic studies preliminary to sclerotherapy and a skilled interventional
      radiologist in order to reduce the number of recurrences.

PMID- 10938704
TI  - [Echographic evaluation of the thymus gland in childhood].
AB  - INTRODUCTION: The thymus is a linphoepithelial organ located mostly in the
      anterior mediastinum and, for a smaller part, in the neck. The gland is
      particularly developed in the fetus and in children, while it shrinks in young
      adults following an involution process. We investigated the US appearance of the
      thymus in normal pediatric subjects to gather information for use in pediatric
      patients with suspected thymus conditions, using a safe, irradiation-free,
      technique. MATERIAL AND METHODS: We performed a US examination of the anterior
      mediastinum and the neck in 30 children (14 males and 16 females) ranging in age
      6 months to 11 years. We used a Sonora LOGIC 700 MD General Electrics unit with
      7.5-13 MHz linear probes and acquired transverse and longitudinal scans on the
      chest wall and the neck, integrated with intercostal scans. RESULTS: The thymus
      had the same echogenicity as the liver parenchyma in 22 children (73.3%), lower
      echogenicity in 2 (6.6%, age range 6-12 months) and higher echogenicity with
      heterogeneous structure in 6 children (20%, age range 8-11 years). The gland was
      in central and symmetric localization in 20 children (66.6%) while it exhibited a
      slight deviation leftwards in 7 (23.3%) and rightwards in 3 children (10%). We
      considered as normal the following values: in the right lobe, 1.4 cm for the AP
      diameter and 2.5 cm for the longitudinal one; in the left lobe, 1.4 cm for the AP
      diameter and 2.9 cm for the longitudinal one. DISCUSSION AND CONCLUSION:
      Radiological studies of the thymus are really difficult to perform because the
      gland is extremely variable in size, extension and shape. The thymus has the same
      echogenicity as the liver parenchyma and lower echogenicity than the thyroid
      parenchyma. We believe that US is an effective technique for studying the thymus
      in all its involution stages and that provides similar information to CT and MRI.
      Also, US does not use radiations and needs no sedation, which improves safety for
      young patients.

PMID- 10938705
TI  - Can benchmarking be applied to radiation protection? And is it useful?
AB  - PURPOSE: Any program of protection from the ionizing radiations used for health
      care must ultimately lead to the total prevention of graduated effects and to the
      limitation of probabilistic effects to acceptable levels. The latter are the more
      dangerous because they may occur even at very low doses and involve the whole
      population including unexposed subjects; these effects may appear in the
      generations to come. The specific protection of the health of operators,
      patients, and the general population, depends on a series of physical-technical
      and bureaucratic-administrative factors. These must be known and applied based on
      precise reference standards, recommended or stated by law, as well as on
      appropriately regulated and controlled procedures. We chose to apply the
      benchmarking method to radiation protection in order to standardize and increase
      the efficacy of prevention and to plan, according to Deming's cycle, the
      continuous improvement of radiation protection performance. METHOD: Benchmarking
      is a qualitative intercomparison method widely used in business economics to
      improve performance referring to best practice and the best in class. When
      applied in a department where all the partners belong (internal benchmarking),
      the method features a subdivision into different (sub)processes integrated
      according to the logic of problem-solving. These stages are: planning: 1)
      identifying benchmarking issues; 2) identifying the participants; 3) deciding the
      data collection method; 4) data collection; analysis: 5) measuring the gap; 6)
      planning future performance; integration: 7) reporting the results; 8) setting
      the functional goals; action: 9) developing and implementing plans; 10) checking
      results and resetting the target. The gross subdivision of resources into human
      and structural permits to check the gap between an actual and an ideal setting
      separately. Thus, the procedures will give information on the human factor which
      will be periodically checked in loco relative to all active and passive conducts,
      while standards will be used to assess the available spaces, facilities and
      equipment, as well as the relative regular activity. Specific physical-technical
      and bureaucratic-administrative indices will be needed in both cases. RESULTS AND
      DISCUSSION: Solving the operators' doubts and consequently decreasing the
      statistical errors and/or the cases of incorrect performance has resulted in
      improved rendered quality, which will be further increased after the planned
      replacement of substandard or unsafe equipment. Meanwhile, the early application
      of equipment quality controls has helped rationalize and markedly decrease
      maintenance costs, which results in possible technologic investment to improve
      emergency imaging. Greater attention to their protection has made patients feel
      an improvement in received quality and has increased empathy in general. Total
      quality, as compared with the best practice, has increased thanks to the positive
      stimulus from standardization, emulation and sharing, and not only to the
      controls performed. It is difficult to evaluate the management indices,
      especially the performance efficacy, that is the relationship between radiation
      protection and results, because the work is in progress and we still lack the
      actual data on the decrease in accidents at work or occupational diseases of the
      operators. Moreover, the epidemiological data on radiation-induced conditions
      will be difficult to collect and interpret, which will make the dynamics of
      lawsuits for unwarranted or excessive exposure a useful and more readily
      available piece of information. Finally, relative to economic results, we would
      like to stress that no additional costs have been necessary to implement safety
      and quality in a setting involving, directly or indirectly, thousands of people.
      (ABSTRACT TRUNCATED)

PMID- 10938706
TI  - [A method for optimizing the estimation of the dose to the patient in traditional
      radiology].
AB  - INTRODUCTION: The method recommended by Report no. 34 (1982) of the International
      Commission on Radiological Protection (ICRP) for patient dose computation in
      diagnostic radiology is based on tabulated dosimetric data obtained from Monte
      Carlo simulations on anthropomorphic phantoms described by simple mathematical
      functions. When computing the dose absorbed by an adult patient, this method
      suffers from two main limitations: first, the geometrical parameters--and in
      particular focus-to-film distance and film size--are fixed, which makes the
      dosimetric data of limited use when the examination geometry differs from the
      ICRP standard. In addition, when patient size and mass differ considerably from
      the corresponding quantities of the mathematically described phantom (the so
      called reference man, with a height of 174 cm and a mass of 70.9 kg) the ICRP
      method may lead to great errors in dose estimate. The aim of the present paper is
      to indicate a method to overcome the above limitations. MATERIAL AND METHODS: The
      algorithm proposed in this work is based on the method suggested by Huda and
      Gkanatsios in order to compute the effective dose through a linear first of the
      energy imparted per unit dose-area product as a function of the half value
      thickness and by using fit coefficients depending on both phantom thickness and
      peak voltage. We devised a procedure to normalize the dose computed with this
      methods with respect to the equivalent effective dose obtained with the ICRP
      method. We therefore determined the dependence of the absorbed dose on focus-to
      film distance, film size and patient anatomy. RESULT AND DISCUSSION: We found
      that--for each value of patient mass--the dose dependence on film size can be
      approximated by a polynomial function, while the dose dependence on focus-to-film
      distance can be approximated by a power law. If the above parameters vary in a
      limited range close to the ICRP standard, a linear fit can be performed without
      introducing a considerable error. The linear fit coefficients, on the other hand,
      were found to depend on the average body surface, a parameter which takes into
      account both patient height and mass. Thus, determining the normalization factor
      for each projection and each view allows to estimate the absorbed dose under
      different geometrical conditions. The method has been verified by considering
      four of the most common X-ray procedures (chest AP, cervical spine LAT, lumbar
      spine AP and head LAT). CONCLUSIONS: The average error on dose estimation is
      about 13%. In the very next future the method will be extended to all the
      projections and views of ICRP Report no. 34, and we plan to integrate the
      described algorithm in a computer program devoted to the automatic computation of
      patient dose.

PMID- 10938707
TI  - [Comparison of mammographic and industrial films in dialysis patients].
AB  - PURPOSE: To optimize the technique for radiographic studies of bone and joint
      damage in renal osteodystrophy. MATERIAL AND METHODS: Sixty-four patients with
      chronic renal failure on dialysis for 0-10 years, were divided into two
      homogeneous groups and submitted to two different radiographic examinations of
      the nondominant hand. Group A patients were examined with a conventional
      radiological unit and an industrial film and a conventional radiological unit
      with a mammographic film with a dedicated screen, while group B patients with a
      mammographic with an industrial film and a conventional radiologic unit with a
      mammographic film with a dedicated screen. The examinations were evaluated by
      three radiologists in a double-blind fashion. RESULTS: Bone conditions such as
      osteoporomalacia, trabecular rarefaction, channel enlargement and intracortical
      absorption were equally demonstrated by mammographic films and the mammograph
      with industrial films. The mammographic film was superior to the mammograph with
      an industrial film in 8 cases, comparable in 25 and inferior in 6, but when
      compared with the conventional radiological unit with an industrial film it was
      superior in 19 cases, comparable in 2 and never inferior. CONCLUSIONS: The
      industrial film without a screen combined with a mammograph is considered the
      gold standard to study fine bone alterations in renal osteodystrophy. However the
      conventional radiological unit with a mammographic film with a dedicated screen
      provides the same results with lower irradiation doses and can therefore be
      considered a good alternative.

PMID- 10938708
TI  - [A visual displayer for publishing radiologic images on the World Wide Web].
AB  - PURPOSE: To present a software suitable for publication of medical images on the
      World Wide Web and compatible with both the DICOM and other popular formats like
      GIF and JPEG. MATERIALS AND METHODS: DICOM viewer is a Java applet, written in
      Java 1.0. The tool offers the capability to publish medical images, to modify
      brightness and contrast (windowing) and to magnify the picture (magnification
      lens). Information related to the image is available for consultation only for
      DICOM images. RESULTS: The viewer was tested with many DICOM files, generated by
      our PACS or downloaded from Internet. It works well with the DICOM 3.0 file
      format, but correct functioning is not granted for previous releases. The
      software was compatible with all the most popular Web browsers (MS Internet
      Explorer 3.0 or newer, Netscape Navigator 4.5 or newer, Sun and HotJava) and it
      works well in Windows, Sun Solaris. Macintosh, Windows CE. A 512 kb image (a
      standard MR image) requires about 5 seconds to be shown on an Intel Pentium II PC
      with 32 Mbyte RAM connected on a 10 Mbit/s Ethernet network. About 3 seconds are
      needed to download the file and about 2 seconds to display the image. Windowing
      and zooming are quick enough. CONCLUSIONS: The applet allows to publish DICOM
      medical images directly on the World Wide Web, without converting them into
      another graphical format. Moreover, it supplies some image processing tools
      common in the radiological environment. The viewer characteristics make it
      suitable for preparing teaching radiology sites or clinical files on the Web. The
      viewer's performance is somewhat poor, particularly on the Internet. Better
      performances are achieved on local area network (intranet). To improve
      performance, we will introduce file compression and rewrite the software in Java
      1.1. The software is available from the author free of charge.

PMID- 10938709
TI  - [Monolateral duplication of the patella. Report of a case].

PMID- 10938710
TI  - [Giant mediastinal chordoma. Description of a case].

PMID- 10938711
TI  - [Aspiration of a foreign body. A rare cause of pneumomediastinum in childhood].

PMID- 10938712
TI  - [Echography of carcinoma of the anal canal before and after conservative
      treatment. Case report].

PMID- 10938713
TI  - [Celiac disease in the adult. Echographic diagnosis in a case].

PMID- 10938714
TI  - [The role of helical computer tomography in pancreatic metastasis of renal
      carcinoma. A rare case and review of the literature].

PMID- 10938715
TI  - [Percutaneous embolization of traumatic aneurysm of the superficial temporal
      artery. Case report].

PMID- 10938716
TI  - [Post-traumatic priapism with high flow treated with embolization with N-butyl
      cyanoacrylate. Apropos of a case].

PMID- 10938717
TI  - [Really an intruder!].

PMID- 10938718
TI  - [Problems in perinatal radiology].

PMID- 10938719
TI  - Generation and functional analysis of distinct macrophage sub-populations from
      goldfish (Carassius auratus L.) kidney leukocyte cultures.
AB  - Three distinct sub-populations of macrophages derived from goldfish kidney
      leukocyte cultures were generated and characterised. The sub-populations
      designated as R1, R2 and R3-type macrophages had distinct morphological,
      cytochemical and flow cytometric profiles, and also differed in their anti
      microbial functions after activation with macrophage activation factors (MAF) and
      bacterial lipopolysaccharide (LPS). The R1-type macrophages were small cells that
      contained acid phosphatase, but lacked myeloperoxidase and non-specific esterase.
      The R2-type macrophages were morphologically similar to mature tissue macrophages
      of mammals, and were positive for acid phosphatase, myeloperoxidase and non
      specific esterase. The R3-type macrophages were round cells with eccentrically
      placed nuclei and resembled mammalian monocytes. This sub-population stained for
      acid phosphatase, myeloperoxidase and non-specific esterase. The R2 and R3-type
      macrophages exhibited distinct functional responses after activation with MAF
      and/or LPS. R2-type macrophages were potent producers of nitric oxide, while R3
      type macrophages produced little or no nitric oxide after activation with MAF and
      LPS. The R2 and R3-type macrophages also exhibited unique respiratory burst
      responses (ROI) after treatment with MAF and/or LPS. After treatment with MAF and
      LPS, activated R2 macrophages were primed for ROI after only 6 h of stimulation
      with the activating agents, and continued to exhibit a strong ROI response for an
      extended cultivation period (48 h). In contrast, activated R3-type macrophages
      showed an early ROI response (6 h after treatment with MAF and LPS), which
      decreased significantly by 48 h after treatment with the activating agents. Our
      results suggest that the analysis of the mechanisms of induction of fish anti
      microbial responses may be dependent upon the concerted actions of functionally
      distinct macrophage sub-populations.

PMID- 10938720
TI  - Spontaneous in vitro angiogenesis in a trout pronephric stromal cell line (TPS),
      and in TPS-haemopoietic co-cultures.
AB  - This study describes angiogenic processes taking place in the in vitro micro
      environment of a trout pronephric stroma cell line (TPS) under specific culture
      conditions, in which fetal calf serum, horse serum and hydrocortisone-sodium-21
      hemisuccinate were used as supplements to the culture medium. When TPS cultures
      were kept in the same flask, i.e. without passages, for longer than 7 months,
      epithelioid cells differentiated into endothelial cells. Early stages of such
      differentiation were characterised by the presence of intracellular tubular
      vacuoles in clusters of neighbouring epithelioid cells. Subsequently, the
      endothelial cells reorganised and gave rise to microvascular structures, which
      branched over and into the TPS multilayers. The lining cells of the
      microvasculature showed typical characteristics of endothelial cells, such as
      ovoid or cubical shape, bundles of microfilaments and microtubules, and
      particularly numerous small vesicles at the apical pole, some of them fused to
      the plasma membrane. Similar angiogenic processes were also observed in long-term
      haemopoietic co-cultures formed by the TPS cell line and trout pronephric cell
      suspensions. Developing haemopoietic cells were observed at the basal pole of the
      vessels, and in the vascular lumen, where some immature cells appeared in close
      contact with the endothelium. These results indicate that the TPS cell line
      contains endothelial cell precursors, which are able to differentiate under
      certain culture conditions.

PMID- 10938721
TI  - Cresolase, catecholase and laccase activities in haemocytes of the red swamp
      crayfish.
AB  - Phenoloxidase activity in crayfish haemocyte lysates and extracts of haemocyte
      membranes were studied using native PAGE and SDS-PAGE gels and staining for
      cresolase, catecholase and laccase activities. The activation of the proenzyme,
      prophenoloxidase to phenoloxidase, in native PAGE was demonstrated following
      exposure to SDS. By staining samples separated in SDS-PAGE followed by
      renaturation, a high molecular mass phenoloxidase activity was identified in both
      the soluble and membrane fractions of haemocyte preparations. The membrane
      associated activity appeared at only relatively high molecular mass (> 300 kDa),
      and could easily be eluted from membranes using detergents or NaCl. Further, this
      membrane-associated activity has a catecholase activity but not the cresolase
      activity seen in the soluble preparations. In addition, several other
      phenoloxidase enzymes were identified with different relative mobilities (250,
      80, 72 and 10 kDa). Crayfish haemocytes also contained laccase activity, thought
      to be restricted to cuticle sclerotisation in the integument. Laccase activity in
      haemocytes might aid in the formation of capsule used to contain pathogens.

PMID- 10938722
TI  - Effects of sea lice (Lepeophtheirus salmonis Kroyer, 1837) infestation on
      macrophage functions in Atlantic salmon (Salmo salar L.).
AB  - Experiments were conducted to determine the effects of sea lice, Lepeophtheirus
      salmonis, on non-specific defence mechanisms in Atlantic salmon, Salmo salar, by
      experimentally infesting hatchery-reared 1 and 2 year old post-smolts, S1 and S2,
      with laboratory grown infective copepodids at moderate to high infection
      intensities ranging from 15-285 lice per fish. The effects of sea lice-induced
      stress were investigated by measuring the blood levels of cortisol and glucose as
      indicators of primary and secondary stress responses, and by changes in
      macrophage respiratory burst activity and phagocytosis as indicators of tertiary
      stress responses as well as non-specific defence mechanisms. Fish were sampled
      prior to sea lice infestation at day 0 and at days 3, 7, 14 and 21 post
      infestation. Sea lice were at copepodid stage at day 3, at chalimus stages at
      days 7 and 14, and at pre-adult stage at day 21. Blood levels of cortisol and
      glucose were found to be significantly increased at day 21 in fish-infested with
      the highest levels. Macrophage respiratory burst and phagocytic activities were
      found to be significantly decreased only at day 21. These results indicate that
      sea lice do not suppress host defence mechanisms during the earlier stages of
      infestation. They do have effects on the development of chronic stress and on the
      host non-specific defence mechanisms soon after the lice reach the pre-adult
      stage.

PMID- 10938723
TI  - Cloning and sequencing hybrid striped bass (Morone saxatilis x M. chrysops)
      transforming growth factor-beta (TGF-beta), and development of a reverse
      transcription quantitative competitive polymerase chain reaction (RT-qcPCR) assay
      to measure TGF-beta mRNA of teleost fish.
AB  - A transforming growth factor (TGF)-beta was isolated and cloned from hybrid
      striped bass (Morone saxatilis x M. chrysops) anterior kidney mononuclear cells.
      This isolate (Genbank accession number AF140363) contains an open reading frame
      of 1146 bases coding for a 382 amino acid protein most similar to rainbow trout
      TGF-beta (57.3 and 78.6% identity with precursor and active protein,
      respectively) and rat TGF-beta 1 (41.1 and 68.8% identity with precursor and
      active protein, respectively). Consensus primers were demonstrated to amplify
      specifically by polymerase chain reaction (PCR), a TGF-beta segment from 14
      species of teleost fish comprising 10 taxonomic families in 7 orders. A reverse
      transcription quantitative competitive polymerase chain reaction (RT-qcPCR) assay
      was devised to measure TGF-beta mRNA expression in teleost fish. Higher levels of
      TGF-beta mRNA expression were detected in mononuclear cells of peripheral blood
      than from spleen or anterior kidney.

PMID- 10938724
TI  - Antibacterial cathepsins in different types of ambicoloured Japanese flounder
      skin.

PMID- 10938725
TI  - Chromatographic separation of trypsin-inhibitory activity of rainbow trout blood
      and seminal plasma.

PMID- 10938726
TI  - Evaluation of immunoglobulins produced in vitro by head-kidney leucocytes of sea
      bass Dicentrarchus labrax by immunoenzymatic assay.

PMID- 10938727
TI  - Long-term immune dysfunction in rainbow trout (Oncorhynchus mykiss) exposed as
      embryos to aflatoxin B1.

PMID- 10938728
TI  - Bath exposure of Atlantic halibut (Hippoglossus hippoglossus L.) yolk sac larvae
      to bacterial lipopolysaccharide (LPS): absorption and distribution of the LPS and
      effect on fish survival.
AB  - Radiolabelled bacterial lipopolysaccharide (3H-LPS) obtained from Aeromonas
      salmonicida subsp. salmonicida was added to the petri dishes containing yolk sac
      larvae of Atlantic halibut (Hippoglossus hippoglossus L.). The larvae were
      exposed either to 6.25, 12.5, 25, 50 or 100 micrograms 3H-LPS ml-1. The uptake
      was both dependent on the LPS concentration and the time of exposure. After 5
      days of exposure, each larva contained 1.8-7.4 ng 3H-LPS dependent on the initial
      concentration. After 10 days of exposure each larva contained 7.0-12.4 ng LPS and
      after 15 days they contained 18.3-34.9 ng 3H-LPS. Fluorescence microscopic
      analysis of sections obtained from larvae exposed to FITC-LPS (25, 50 and 100
      micrograms ml-1) for 5, 10 and 15 days, revealed fluorescence in intestinal
      epithelial cells, cells in the connective tissue adjacent to the intestine, in
      cells located between the integumental layer and yolk sac, and in some epithelial
      cells in the integument. By use of immunohistochemical techniques, LPS was
      confined to intestinal epithelial cells, lumen of excretory duct and in numerous
      cells in the epidermal layer. Control specimens did not contain fluorescence or
      were immunohistochemically negative for LPS. In groups of larvae exposed to 12.5,
      25, 50 and 100 micrograms LPS ml-1, the survival was significantly increased
      after exposure to 50 and 100 micrograms LPS ml-1 from day 20 (96 d degree) and
      throughout the yolk sac period compared to untreated larvae.

PMID- 10938729
TI  - Three monoclonal antibodies to the VHS virus glycoprotein: comparison of
      reactivity in relation to differences in immunoglobulin variable domain gene
      sequences.
AB  - Three monoclonal antibodies (MAbs) to the VHSV G protein were compared in
      different immunoassays and the variable domain cDNA sequences from the respective
      immunoglobulin (Ig) genes were determined. One MAb (IP1H3) was non-neutralising
      and recognised different virus isolates equally well in ELISA. The other two were
      neutralising and recognised the same or closely related epitopes. One of these
      two MAbs (3F1H10) was more restricted in its ability to neutralise heterologous
      VHSV isolates than the other (3F1A2). A semi-quantitative relationship between
      binding of the two neutralising MAbs in ELISA and their neutralising activity was
      evident. Binding kinetic analyses by plasmon resonance identified differences in
      the dissociation rate constant (kd) as a possible explanation for the different
      reactivity levels of the MAbs. The Ig variable heavy (VH) and light (V kappa)
      domain gene sequences of the three hybridomas were compared. The inferred amino
      acid sequence of the two neutralising antibody VH domains differed by three amino
      acid residues (97% identity) and only one residue difference was evident in the V
      kappa domains. In contrast, IP1H3 shared only 38 and 39% identity with the 3F1A2
      and 3F1H10 VH domains respectively and 49 and 50% identity with the 3F1A2 and
      3F1H10 V kappa domains respectively. The neutralising antibodies were produced by
      hybridomas originating from the same fusion and the high nucleotide sequence
      homology of the variable Ig gene regions indicated that the plasma cell partners
      of the hybridomas originated from the same virgin B lymphocyte. The few
      differences observed in the VH and V kappa amino acid sequences were probably due
      to somatic mutations arising during affinity maturation and might explain the
      observed reactivity differences between the two MAbs.

PMID- 10938730
TI  - Spontaneous cytotoxic activity of eosinophilic granule cells separated from the
      normal peritoneal cavity of Dicentrarchus labrax.
AB  - In this study the spontaneous in vitro cytotoxic activity to tumour cell lines,
      (K562), by unstimulated sea bass (Dicentrarchus labrax) leukocytes was examined
      by trypan blue exclusion test and lactate dehydrogenase release assay. A high
      anti-tumour cell line activity of resident peritoneal leukocytes was found at an
      effector to target ratio (E:T) of 25:1 after incubation for 2 h at 18 degrees C.
      Rabbit and sheep erythrocytes were not lysed. A low activity was displayed by
      head kidney and spleen cell populations whereas blood leukocytes revealed no
      significant activity. The effect of E:T ratio on cytotoxicity as well as
      microscopy observations suggested that the cytotoxic reaction required effector
      target cell contact. Eosinophilic granule cells, isolated on a Percoll density
      gradient from a peritoneal wash, appeared to be responsible for the in vitro
      cytotoxic activity.

PMID- 10938731
TI  - Separation of European flat oyster, Ostrea edulis, haemocytes by density gradient
      centrifugation and SDS-PAGE characterisation of separated haemocyte sub
      populations.
AB  - A two-step gradient centrifugation with Percoll and Ficoll successively as
      density medium was developed to separate European flat oyster, Ostrea edulis,
      haemocytes into three sub-populations representing granulocytes, large
      hyalinocytes and small hyalinocytes, respectively. After a Percoll gradient
      centrifugation, granulocytes and agranulocytes were separated and a pure fraction
      of granulocytes was obtained. The agranulocytes were further separated by
      centrifugation through a Ficoll gradient, and two haemocyte subpopulations
      representing large hyalinocytes and small hyalinocytes were obtained. No
      significant impact on the haemocyte viability was detected after separation with
      this two-step density gradient centrifugation. The three haemocyte sub
      populations showed different protein patterns in SDS-PAGE.

PMID- 10938732
TI  - Biochemical and functional characterisation of macrophage stimulating factors
      secreted by mitogen-induced goldfish kidney leucocytes.
AB  - Mitogen-stimulated goldfish kidney leucocytes secrete a number of different
      macrophage activation factors (MAF) that induce profound physiological changes in
      macrophages. MAF produced by goldfish kidney leucocytes was characterised using
      fast performance liquid chromatography (FPLC) and bioassays that measured MAF
      induced respiratory burst (RB) and nitric oxide (NO) responses of activated
      macrophages. Mitogen-induced fish kidney leucocyte supernatants were fractionated
      using gel permeation FPLC (GP-FPLC) and the ability of different fractions to
      induce NO or RB measured. A MAF of M(r) 50 kD, that induced a potent nitric oxide
      response in both a long-term goldfish macrophage cell line (GMCL) and in in vitro
      derived fish kidney macrophages (IVDKM) was identified. The GP-FPLC partially
      purified 50 kD MAF activity occasionally induced significantly higher nitric
      oxide production than that of the crude MAF preparations. This increase in the NO
      inducing activity was due to segregation of the 50 kD MAF from a novel macrophage
      deactivating molecule of M(r) 10-12 kD present in crude MAF preparations. This 10
      12 kD molecule was shown to inhibit nitric oxide production in cytokine-activated
      goldfish macrophages. Mitogen-induced fish kidney leucocyte supernatants
      contained two distinct MAFs that induced the respiratory burst in GMCL and IVDKM:
      the 50 kD and 30 kD proteins. The partially purified 30 kD MAF primed goldfish
      macrophage for increased RB activity after only 6 h of treatment, and continued
      to augment the RB activity after 24 h of stimulation. In contrast, the GP-FPLC
      partially purified 50 kD molecule also primed the RB after only 6 h of
      stimulation, but subsequently deprimed the RB after 24 h of stimulation, an
      effect similar to that observed for crude MAF preparations. The 50 kD MAF
      activity was further purified using chromatofocusing FPLC (C-FPLC) using basic pH
      gradients and was shown to consist of two distinct NO-inducing molecules (> pI
      9.3). Mitogen-stimulated fish kidney leucocytes secrete several factors that
      profoundly affect the anti-microbial responses of teleost macrophages and which
      undoubtedly are responsible for regulating teleost macrophage function in vivo.

PMID- 10938733
TI  - Immunocytochemical detection of Ig-positive cells in blood, lymphoid organs and
      the gut associated lymphoid tissue of the turbot (Scophthalmus maximus).
AB  - The present study was designed to search for the sites of the B-cell lineage in
      the different lymphoid organs of turbot (Scophthalmus maximus) by
      immunoperoxidase staining with a rabbit polyclonal antiserum against
      deglycosylated turbot IgM (TUDG-6). A turbot immunoglobulin (Ig) fraction,
      isolated by protein A, was checked for purity by gel filtration and SDS-PAGE
      under reducing conditions. The turbot IgM was deglycosylated and used to raise an
      antiserum. The antiserum titre was evaluated in ELISA. It was then used to
      analyse turbot peripheral blood leucocytes for membrane and cytoplasmic Ig and
      for immunohistochemistry with turbot lymphoid tissues. Very low numbers of Ig+
      cells were found in thymus sections. In sections of spleen, Ig+ cells were
      observed in white pulp, around ellipsoids but were mostly concentrated and
      associated with melanomacrophage centers (MMCs). The lymphoid Ig+ cells in the
      kidney tended to be dispersed among haematopoietic and granulopoietic cell
      populations and were in intimate association with the MMCs and blood vessels.
      This association between MMCs and Ig+ cells in the spleen and the kidney, is
      discussed with respect to the role played by these organs in the immune system of
      fish. Last, the lymphoid population in the gut associated lymphoid tissue (GALT)
      of turbot was characterised with respect to staining for Ig. Immunoreactive cells
      were rarely detected in the epithelial layer although many lymphocytes were
      present, but they were frequently observed in the lamina propria, presumably as
      part of the GALT and involved in mucosal immune responses.

PMID- 10938734
TI  - In vitro modulation of fish phagocytic cells by beta-endorphin.
AB  - The activation of rainbow trout, Oncorhynchus mykiss, and carp, Cyprinus carpio,
      phagocytic cells by synthetic chum salmon, O. keta, beta-endorphin was analysed
      in vitro. Rainbow trout head kidney leukocytes were cultured in RPMI 1640 medium
      containing 1, 10, 50 or 100 ng ml-1 of chum salmon beta-endorphin and the
      production of superoxide anion was measured via the reduction of nitroblue
      tetrazolium (NBT) in vitro. Macrophages incubated with 10 ng ml-1 up to 100 ng ml
      1 of beta-endorphin showed an increase in their production of superoxide anion in
      comparison with control macrophages which were cultured without hormone. beta
      endorphin also increased the production of superoxide anion in phagocytic cells
      prepared from kidney of carp. This stimulation was inhibited by naloxone.
      Phagocytic cells treated with beta-endorphin also displayed increased phagocytic
      activity and phagocytic index. These results showed that beta-endorphin in lower
      vertebrates activates the function of phagocytic cells in vitro.

PMID- 10938735
TI  - Complement system of bony and cartilaginous fish.
AB  - Accumulating evidence indicates that the complement system experienced a
      discontinuous development at an early stage of vertebrate evolution.
      Invertebrates such as echinoderms and ascidians, and the most primitive extant
      vertebrates, the cyclostomes, seem to have a primitive complement system equipped
      only with the alternative and lectin pathways. In contrast, cartilaginous fish
      and higher vertebrates seem to have a modern complement system which has two
      additional pathways, namely the classical and lytic pathways. Recent molecular
      analyses of the complement system of bony and cartilaginous fish have not only
      confirmed the above conclusion, but also revealed a unique characteristic of the
      complement system of fish, where certain key component genes are duplicated. The
      complement system seems to play a more pivotal role in body defence in fish,
      whose adaptive immunity is considered to be at a relatively undeveloped state.

PMID- 10938736
TI  - Molecular cloning and expression analysis of carp (Cyprinus carpio) interleukin-1
      beta, high affinity immunoglobulin E Fc receptor gamma subunit and serum amyloid
      A.
AB  - Suppression subtractive hybridisation (SSH) is a powerful means to identify genes
      of cytokines and other genes that express small amount of mRNA. In this study,
      cDNA of normal fish (carp) head kidney cells (HKC) was subtracted from pooled
      cDNA of HKC and peritoneal cell (PC) obtained from fish which had been injected
      with sodium alginate (SA) and scleroglucan (SG) 3-48 h earlier. This subtraction
      produced 248 clones of cDNA fragments. After sequencing some of the fragments of
      interest were used as probes, and yielded full-length cDNAs homologous to
      mammalian interleukin-1 beta (IL-1 beta), the gamma subunit of high affinity Fc
      receptor for IgE (Fc epsilon RI gamma) and serum amyloid A (SAA); these were
      cloned and sequenced. Carp IL-1 beta shows 21.8-24.7% amino acid identities to
      mammalian mature IL-1 beta, and lacks a signal sequence, which is consistent with
      mammalian IL-1 beta. Carp Fc epsilon RI gamma, which was the first cloned non
      mammalian Fc receptor subunit, shows 39.3-40.4% amino acid identities to
      mammalian Fc epsilon RI gamma, and contains the immunoreceptor tyrosin-based
      activation motif characteristic of the signal transduction subunit of antigen-
      and Fc-receptors. Carp SAA is most similar to mammalian acute phase responsive
      type SAA with 53.0-55.3% amino acid identities. Both SA-elicited and SG-elicited
      PC expressed higher amounts of IL-1 beta and SAA mRNA compared to saline-injected
      fish HKC and PC, indicating that these proteins are associated with inflammatory
      responses, similar to mammalian homologues. Fc epsilon RI gamma was
      constitutively expressed in leucocytes and not immunopotentiator-responsive, but
      this indicates that Fc receptor including Fc epsilon RI gamma subunit is likely
      functional in the carp immune system.

PMID- 10938737
TI  - Antibacterial proteins in rainbow trout, Oncorhynchus mykiss.
AB  - Antibacterial proteins are an important part of the innate immune system for all
      animals. They have been extensively studied in mammals, amphibians and
      invertebrates, but have received only scant attention in fish. Their expression
      and processing, however, provide a way of monitoring defence vigour during
      development or with seasonal changes in physiology. The aim of the present work
      was to identify and characterise antibacterial proteins in rainbow trout. In
      vitro analyses of extracts of the peripheral blood leucocytes, head kidney
      leucocytes and mucus from adult unstimulated (non-immune) fish showed marked
      antibacterial activity against Gram positive bacteria. Fractionation by ion
      exchange chromatography and RP-HPLC of head kidney extracts showed the presence
      of two forms of lysozyme but no constitutively expressed antimicrobial proteins
      of < 10 kDa. By contrast, chromatographic analyses of mucus revealed at least
      four antibacterial proteins. Two are conventional lysozymes, a third is an
      unusual lysozyme-like protein with a low isoelectric point, and the fourth is a
      highly hydrophobic, cationic peptide of c. 3 kDa.

PMID- 10938738
TI  - Genes for three different isoforms of transforming growth factor-beta are present
      in plaice (Pleuronectes platessa) DNA.
AB  - Although transforming growth factor-beta (TGF-beta) genes have been described in
      several species of fish, whether an individual fish possesses more than one
      member of this multigene family has yet to be established. During this study,
      three DNA fragments were isolated from the plaice (Pleuronectes platessa) by
      homology cloning. Sequence analysis revealed that each fragment closely resembled
      a distinct member of the TGF-beta family. Each putative plaice TGF-beta clustered
      individually with a different TGF-beta subgroup during phylogenetic analysis
      suggesting that these may be the plaice homologues of vertebrate TGF-beta 1/4/5, 
      beta 2 or -beta 3. The first direct evidence for the presence of multiple TGF
      beta genes in a single fish species is presented.

PMID- 10938739
TI  - Identification of carp proopiomelanocortin-related peptides and their effects on
      phagocytes.
AB  - We report the immunomodulating effects of proopiomelanocortin (POMC)-related
      peptides on phagocytic cells in carp. The complete amino acid sequences of two
      carp POMCs (I and II) were deduced from the nucleotide sequences after cDNA
      cloning. Both POMCs consist of 194 amino acids (91% sequence identity) including
      identical alpha-melanotropin (MSH) and beta-endorphin (EP). All hormonal peptides
      derived from two POMCs were identified by mass spectrometry after separation by
      high-performance liquid chromatography of an acid-acetone extract from a single
      pituitary. These peptides were alpha-MSH, N-Des-Ac-alpha-MSH, di-Ac-alpha-MSH,
      beta-MSH I, beta-MSH-II, N-Ac-beta-EP(1-29), corticotropin-like intermediate lobe
      peptide I and II and N-terminal peptide of POMC I and II. The immunomodulating
      effects of synthetic MSHs and EPs on phagocytic cells from carp head kidney were
      examined. Di-Ac-alpha-MSH, beta-MSH I, N-Ac-beta-EP(1-29) and beta-EP(1-29)
      increased the production of superoxide anion at 0.1-100 ng ml-1 for these MSHs
      and 1-100 ng ml-1 for EPs in RPMI 1640 medium.

PMID- 10938740
TI  - High dietary intake of alpha-tocopherol acetate enhances the non-specific immune
      response of gilthead seabream (Sparus aurata L.).
AB  - To determine the effects of three high levels of dietary intake of alpha
      tocopherol acetate (vitamin E) on the non-specific immune response of gilthead
      seabream (Sparus aurata L.), specimens were fed a commercial diet (100 mg alpha
      tocopherol kg-1) as control, or vitamin E supplemented diets (600, 1200 or 1800
      mg alpha-tocopherol acetate kg-1) for 15, 30 or 45 days. Growth, serum alpha
      tocopherol levels, natural haemolytic complement activity and head-kidney
      leucocyte migratory, respiratory burst and phagocytic activities were studied at
      each of the assay times. A positive correlation between alpha-tocopherol acetate
      intake and serum alpha-tocopherol levels was observed, the increase being linked
      to both the dosage and length of treatment. Specimens fed the diet supplemented
      with 600 mg vitamin E kg-1 showed no enhancement in any of their immune
      parameters, while those fed the diet supplemented with 1200 mg vitamin E kg-1
      presented a slightly higher (but not statistically significant) specific growth
      rate than fish fed the other diets. In addition, serum haemolytic activity and
      the phagocytosis of head-kidney leucocytes were enhanced by the dietary intake of
      1200 mg vitamin E kg-1 after 30 and 45 days of treatment, although leucocyte
      migration and respiratory burst activity remained unaffected. The highest vitamin
      E dietary dose used, 1800 mg kg-1, unexpectedly provoked no immunostimulation.
      These results indicate that a moderate level of vitamin E in the diet (1200 mg kg
      1) stimulates the seabream's non-specific immune system after 30 days of
      administration. Lower or higher vitamin E concentrations may not be so effective,
      because of an imbalance in the vitamin E ratio with other antioxidants. The
      proposed dietary levels of vitamin together with the indicated administration
      time could be useful for reducing the susceptibility of farmed fish to infectious
      diseases.

PMID- 10938741
TI  - Molecular isolation and characterisation of carp transforming growth factor beta
      1 from activated leucocytes.
AB  - The transforming growth factor (TGF beta) family of proteins are a set of
      pleiotropic secreted signalling molecules with unique and potent immunoregulatory
      properties. In this study the molecular cloning of carp TGF beta 1 is reported. A
      partial cDNA of the TGF beta protein was initially identified from a cDNA pool,
      obtained by subtracting the cDNAs from Con A-induced carp head kidney leucocytes
      from uninduced carp head kidney leucocyte cDNA. The entire coding sequence was
      assembled by sequencing both ends of the cDNA clone by using an anchored PCR
      reaction. Sequence analysis revealed an ORF encoding a protein of 376 amino
      acids, containing the similar unique pattern of conserved cysteines (seven out of
      nine) in the cysteine knot structure which exists in all known TGF beta proteins.
      Compared with other animal TGF beta s, the cDNA clone shows approximately 59-42,
      40-38 and 37-36% amino acid identity with TGF beta 1, TGF beta 3 and TGF beta 2
      respectively. Carp TGF beta 1 is expressed at low levels in carp head kidney,
      spleen, egg and liver, whereas its messenger RNA level is increased after
      activation of the head kidney leucocytes with Con A. Sequence analysis and
      pattern of expression suggests that this is the carp TGF beta 1.

PMID- 10938742
TI  - Susceptibility of juvenile and sub-adult Atlantic halibut (Hippoglossus
      hippoglossus L.) to infection by Vibrio anguillarum and efficacy of protection
      induced by vaccination.
AB  - Experimental bath challenge of juvenile and sub-adult Atlantic halibut with
      Vibrio anguillarum induced severe mortalities of 47 and 80%, respectively.
      However, animals vaccinated with a commercial V. anguillarum vaccine demonstrated
      excellent protection against the disease (100% RPS). This study also describes
      the gross pathology and histological changes associated with this infection. A
      loss of coordination, haemorrhage at the fin base and splenomegaly were frequent
      findings. Serum agglutinating activity demonstrated a rise following vaccination,
      the mean log2 titre rising from 3.8 to 8.4. This was associated with a
      significant rise in antibody-mediated complement killing ability of immune serum
      when compared to non-immune serum.

PMID- 10938743
TI  - Immunopurification of T-cells from sea bass Dicentrarchus labrax (L.).
AB  - The monoclonal antibody DLT15, specific for thymocytes and peripheral T-cells of
      the teleost fish Dicentrarchus labrax (sea bass), was used to purify
      immunoreactive cells from blood and gut-associated lymphoid tissue. The
      purification was performed by immuno-magnetic sorting of leucocyte fractions
      enriched by Percoll density gradient centrifugation, and the purity of the
      isolated cells was estimated by cytofluorimetric analysis. Following a single
      step, the percentage of DLT15-purified cells was 88 +/- 10% for gut-associated
      lymphoid tissue and 79 +/- 18% for blood leucocytes. DLT15-purified cells from
      gut-associated lymphoid tissue were employed for RNA extraction and cDNA
      synthesis. In RT-PCR experiments using as primers degenerate oligonucleotides
      corresponding to the peptide sequence MYWY and VYFCA of the trout TcR beta chain,
      a 203 bp product was amplified. When sequenced, the cDNA was found to show 60%
      nucleotide identity to the trout TcRV beta 3. By 3'-RACE the cDNA was elongated
      to obtain the TcR constant region, with high similarity to other fish TcR
      sequences. These results strongly suggest that cells recognised by DLT15 are
      putative T lymphocytes.

PMID- 10938744
TI  - Analysis of a cDNA sequence encoding the immunoglobulin heavy chain of the
      Antarctic teleost Trematomus bernacchii.
AB  - A spleen cDNA library was constructed from the Antarctic teleost Trematomus
      bernacchii and immunoscreened with rabbit IgG specific for T. bernacchii Ig heavy
      chain. Eleven cDNA clones, varying in size and encoding the entire heavy chain or
      parts of it, were isolated. Here the complete nucleotide and deduced amino acid
      sequences of clone 2C2 encoding the secretory IgH chain form are reported.
      Comparison of the amino acid sequence of the entire constant region of the T.
      bernacchii Ig heavy chain with those from other teleosts and two holostean fish
      showed percent identity ranging 53.6-60.6%, with the highest values found for
      Salmoniformes. The multiple sequence alignment revealed the presence of two
      remarkable insertions: one at the VH-CH1 boundary and a second one, not found in
      any other IgM heavy chain, localised at the CH2-CH3 boundary. The latter occurred
      in the region proposed to act as a 'hinge', and resulted in a CH2-CH3 hinge
      peptide longer than any other IgM hinge. Differences were also found in the
      number and position of putative N-glycosylation sites of the compared sequences.
      It is suggested that the unusual features found in the T. bernacchii Ig heavy
      chain might contribute to the flexibility of the Ig molecule and help understand
      more about the adaptation of Ig molecules to the polar sea environment.

PMID- 10938745
TI  - Suppression of the humoral immune response of Atlantic salmon, Salmo salar L. by
      the 64 kDa serine protease of Aeromonas salmonicida.
AB  - Bacteria-free supernatants of broth cultures of Aeromonas salmonicida inhibited
      the humoral immune response, but not the cell-mediated immune response, of
      Atlantic salmon to bacteriophage MS2. The immunosuppressive factor was the 64 kDa
      serine protease secreted by A. salmonicida. The suppressive activity was not due
      to degradation of epitopes of MS2, and although serine protease degraded the
      heavy chain of salmon IgM in vitro there was no evidence for significant
      degradation in vivo. The principal lethal toxin of A. salmonicida, the
      glycerophospholipid: cholesterol acyltransferase did not inhibit the immune
      response of salmon.

PMID- 10938746
TI  - Carp interleukin-1 beta in the role of an immuno-adjuvant.

PMID- 10938747
TI  - Outer membrane proteins of Aeromonas hydrophila induce protective immunity in
      goldfish.

PMID- 10938749
TI  - Effects of pH, temperature and salinity on immune parameters of the freshwater
      prawn Macrobrachium rosenbergii.

PMID- 10938748
TI  - Molecular cloning and expression analysis of the putative carp (Cyprinus carpio)
      pre-B cell enhancing factor.

PMID- 10938750
TI  - Initial rollover effectiveness evaluation of an alternative seat belt design for
      agricultural tractors.
AB  - A test program was conducted to determine the effectiveness of a seat belt
      restraint in preventing occupant movement in a rollover accident. A baseline type
      2 seat belt (pelvic and torso restraint), and an improved type-2 seat belt
      restraint, both designed to restrict occupant motion in a rollover accident, were
      tested in a rollover restraints tester (RRT). Each seat belt was placed on a H
      III 50th percentile male dummy and testing conducted at a single roll rate and
      two D-ring adjustment positions. Each test simulated what was approximately a 260
      degrees per second rollover parallel to the longitudinal axis of the tractor with
      the top of the ROPS impacting the ground after 180 degrees of roll. Forces on the
      dummy's head and neck were measured, and video was taken to measure the head
      motion in the x-, y-, and z-axis of the dummy. The average vertical, forward, and
      lateral head movement in the baseline seat belt was 144, 222, and 184 mm,
      respectively, when the adjustable D-ring anchorage supporting the shoulder belt
      was in its lowest position. At the lowest D-ring height, the shoulder belt became
      ineffective and the seat belt performance became similar to a type-1 restraint
      (required for tractors with ROPS) resulting in increased vertical, forward, and
      lateral movement. The improved restraint reduced vertical head movement by as
      much as 75% without increasing head and neck loads above established injury
      criteria. Testing seat belts for rollover effectiveness will become increasingly
      important as seat belt usage on tractors with ROPS increases.

PMID- 10938751
TI  - Prevention effectiveness of rollover protective structures--Part I: Strategy
      evolution.
AB  - This is the first of three articles that evaluate the health and economic
      consequences of the use of rollover protective structures (ROPS) on agricultural
      tractors. The effectiveness of ROPS delivered through alternative intervention
      strategies is the subject of the three-part study. This part of the study reviews
      and assesses the evolution of interventions that are known to prevent injuries
      incurred as a result of tractor overturns. The method used is historical analysis
      framed against a prevention effectiveness model used by the U.S. Centers for
      Disease Control and Prevention. Two intervention strategies were found to be
      potentially effective in preventing injuries from tractor overturns. These
      strategies are either to install a ROPS on tractors that lack a ROPS or to
      replace the tractor with one that has a ROPS already mounted. Other prevention
      factors include the effectiveness and use of seatbelts and the integrity of the
      ROPS system during an overturn.

PMID- 10938752
TI  - Prevention effectiveness of rollover protective structures--Part II: Decision
      analysis.
AB  - This is the second of three articles that evaluate the consequences of using
      rollover protective structures (ROPS) on agricultural tractors. It presents the
      results of a decision analysis that compares three strategies for preventing
      injuries when agricultural tractors without ROPS overturn. The three strategies
      examined are "do nothing", "install ROPS", and "replace tractor". The strategies
      are implemented over a five-year period and health outcomes expressed as fatal
      and nonfatal injuries are calculated over a 23-year period. The "do nothing"
      strategy would result in 1,450 fatalities and 1,806 nonfatal injuries, while the
      "install ROPS" strategy would prevent 1,176 fatalities and 957 nonfatal injuries,
      and the "replace tractor" strategy would prevent 1,188 fatalities and 967
      nonfatal injuries. The latter two strategies reflect more than an 80% reduction
      in fatalities and about 53% reduction in nonfatal injuries. The study does not
      consider overturn injuries that result from tractors lacking ROPS and for which
      ROPS are unavailable.

PMID- 10938753
TI  - Prevention effectiveness of rollover protective structures--Part III: Economic
      analysis.
AB  - The purpose of this part of the study is to assess the costs and benefits of
      either installing rollover protective structures (ROPS) on tractors lacking ROPS
      and for which ROPS are available or replacing the tractors with newer ROPS
      equipped ones, relative to doing nothing. The methods used are cost-effectiveness
      and cost-benefit analyses. The cost-effectiveness analysis shows that compared to
      the "do nothing" strategy, the "install ROPS" strategy would cost $489,373 per
      injury averted and the "replace tractor" strategy would cost $14.3 million per
      injury averted over a 23-year period. The cost-benefit analysis shows that
      compared to the "do nothing" strategy, the "install ROPS" strategy would save
      society $1.5 billion while the "replace tractor" strategy would cost society
      $18.7 billion. While both the "install ROPS" and the "replace tractor" strategies
      are effective at saving lives and preventing injuries, this study has concluded
      that the preferred strategy in terms of cost-effectiveness is to "install ROPS"
      on tractors lacking them and for which ROPS are available.

PMID- 10938754
TI  - Evaluation of the Farm and Agricultural Injury Classification Code and follow-up
      questionnaire.
AB  - The Farm and Agricultural Injury Classification (FAIC) code was developed
      specifically to identify and classify all agricultural injuries of interest to
      agricultural safety and health professionals. The FAIC code overcomes fundamental
      problems of classifying agricultural-related injuries by grouping incidents into
      categories describing actual exposures encountered on farms and in agricultural
      work. The successful application of the FAIC code depends largely on a
      researcher's ability to obtain appropriate information to correctly use the code.
      The purpose of this research project was to: (1) compare data obtained through a
      newly developed FAIC follow-up questionnaire (FQ) with data from the Penn State
      Agricultural Injury Database (AID); and (2) test FAIC Code utility, reliability,
      and construct validity with agricultural safety and health professionals. The FQ
      improved classification of 57% of cases in the Penn State AID. A majority of
      agricultural health and safety professionals understood and used the FAIC coding
      system, without training, to code an average of 75% of the test cases the same as
      the researcher. A large majority of the professionals that participated in this
      study judged the FAIC code and the accompanying materials to be very useful.

PMID- 10938755
TI  - Imperatives for saving lives.

PMID- 10938756
TI  - Health and environment of rural families: results of a Community Canvass survey
      in the Prairie Ecosystem Study (PECOS).
AB  - This cross-sectional survey was conducted as Phase I of the Prairie Ecosystem
      Study (PECOS): Environmental Pesticide Exposure and Human Health. In November of
      1995, community volunteers delivered a self-administered household questionnaire
      to 1185 rural households in southern Saskatchewan, Canada. The survey provided a
      broad description of the general health and the physical environment of 511 men,
      499 women, and 393 children (< 18 years of age) residing in 549 respondent
      households in the rural study area (population density of about one person/km2).
      Families in the respondent households resided on a farm, in town or both. Of the
      369 households that operated a farm, 25.2% of the households did not list the
      farm as their primary household. Residents of both farming and non-farming
      households reported contact with pesticides and fertilizers through home or
      garden use. History of smoking was greater among men and women from non-farming
      households. The most commonly reported health problems among the children were a
      history of bronchitis, asthma, skin allergies, pneumonia, and hay fever. The most
      frequently reported health problems among the men were a history of high blood
      pressure, bronchitis, pneumonia, hearing problems, and stress; and among the
      women were a history of bronchitis, high blood pressure, shortness of breath, and
      pneumonia. Compared to farming households, more members of non-farming households
      reported a history of respiratory problems, particularly bronchitis among the
      women and children. Overall, there were important differences in the smoking
      history, the occupational use of pesticides and fertilizers, and the general
      health status between the farming and non-farming households and individuals in
      this rural population.

PMID- 10938757
TI  - Assessment of the condition of Iowa augers, auger-related injuries, and farmers'
      perceptions about auger-related injuries.
AB  - This study provides an insight into auger-related injuries, Iowa farmers'
      perceptions of auger-related injuries and the condition of augers used in Iowa
      agriculture. Specific auger-related injury data (437 records) from the Iowa
      Department of Public Health (IDPH) was examined and interpreted. The most likely
      body part injured was the finger and 11:00 A.M., 3:00 P.M., and 5:00 P.M. were
      the times of the day with the highest number of injuries reported. In addition, a
      survey was administered to 400 farmers to ascertain their awareness of auger
      related injuries and to determine the condition of their augers. Farmers'
      perceptions of what body part is most likely to be injured by an auger and the
      level of severity expected from those injuries coincided with injury records from
      1993 to 1997. A total 34% of the primary and secondary augers reported were
      unshielded or without guarding. This assessment provides insight for development
      of intervention countermeasures to reduce auger-related injuries.

PMID- 10938758
TI  - An analysis of injury deaths on Florida farms for years 1989 through 1998.
AB  - The purpose of this study was to analyze injury deaths on Florida farms for years
      1989 through 1998. A review of death certificates was undertaken for children, 0
      to 17 years, and adults, ages 18 and older. There were a total of 231 injury
      deaths during this time period. Twenty deaths were in children and 211 deaths
      were in adults. The leading cause of death was machinery for both children and
      adults. Farmworkers between the ages of 60 to 89 were more likely to die of
      tractor deaths than other adult age groups. In addition, adult males were more
      likely to die on Florida farms than adult females, however, females were more
      likely to die as a result of a homicide. This study begins the injury related
      surveillance efforts of the Deep South Agricultural Health and Safety Center.

PMID- 10938759
TI  - Evaluation of the Agricultural Safety and Health Best Management Practices
      Manual.
AB  - The Agricultural Safety and Health Best Management Practices (ASHBMP) Manual was
      developed as an alternative intervention tool to help identify and correct
      farmwork hazards. A modified pretest-posttest control group experimental design
      was used to test the effectiveness of the manual with three intervention groups
      and a control. Testing consisted of conducting baseline and post-intervention
      audits on 150 farms in Pennsylvania. Significant differences were found among
      groups of farmers who were given the ASHBMP Manual and those who were not given
      the manual. The results of the data analysis also showed a positive significant
      difference among farmers who reduced their farm hazard levels through use of the
      ASHBMP Manual over farmers who received the Control (traditional safety fact
      sheets). The data supports the conclusion that the ASHBMP Manual is an effective
      tool for helping farmers reduce workplace hazards.

PMID- 10938760
TI  - Optical glucose sensing in biological fluids: an overview.
AB  - Recent technological advancements in the photonics industry have led to a
      resurgence of interest in optical glucose sensing and to realistic progress
      toward the development of an optical glucose sensor. Such a sensor has the
      potential to significantly improve the quality of life for the estimated 16
      million diabetics in this country by making routine glucose measurements more
      convenient. Currently over 100 small companies and universities are working to
      develop noninvasive or minimally invasive glucose sensing technologies, and
      optical methods play a large role in these efforts. This article reviews many of
      the recent advances in optical glucose sensing including optical absorption
      spectroscopy, polarimetry, Raman spectroscopy, and fluorescent glucose sensing.
      In addition a review of calibration and data processing methods useful for
      optical techniques is presented.

PMID- 10938761
TI  - Zinc biosensing with multiphoton excitation using carbonic anhydrase and improved
      fluorophores.
AB  - Previously, we had shown that the zinc-dependent binding of certain fluorescent
      aryl sulfonamide inhibitors could be used with apocarbonic anhydrase II to
      transduce the level of free zinc as a change in the fluorescence of the
      inhibitor. While inhibitors such as dansylamide, ABD-M, and ABD-N made possible
      quantitation of free zinc in the picomolar range with high selectivity, they have
      only modest absorbance which limits their utility. We describe here the synthesis
      and properties of two new probes, Dapoxyl sulfonamide and BTCS, and their use in
      zinc biosensing. Dapoxyl sulfonamide exhibits a dramatic increase and blue shift
      in its emission upon binding to holocarbonic anhydrase II, as well as a 20-fold
      increase in lifetime: it is thus well suited for quantitating free Zn(II) down to
      picomolar ranges. The anisotropy of BTCS increases fivefold upon binding to the
      holoprotein, making this probe well suited for anisotropy-based determination of
      zinc. BTCS and ABD-N are efficiently excited with two photon excitation using 1.5
      ps pulses from a titanium sapphire laser, and exhibit the increased zinc
      dependent anisotropy response anticipated on the basis of photoselection.

PMID- 10938762
TI  - Super-resolution measurements with evanescent-wave fluorescence excitation using
      variable beam incidence.
AB  - The evanescent wave (EW) elicited by total internal reflection of light
      selectively excites fluorophores in an optical slice above a reflecting
      dielectric interface. EW excitation eliminates out-of-focus fluorescence present
      in epiillumination microscopy, and--close to the coverslip--can offer a fivefold
      enhancement of axial optical sectioning compared to confocal and two-photon
      microscopy. The decay length of the evanescent field is a function of the
      refractive indices and light wavelength involved, and is modulated by the beam
      angle. EW microscopy was used to study the distribution and concentration of
      fluorophores at or near the interface in the presence of high concentrations in
      bulk solution. We modified an upright microscope to accommodate the condenser
      optics needed for EW excitation. Systematic variations of the angle of incidence
      were attained using an acousto-optical deflector, telecentric optics, and a
      hemicylindrical prism. The three-dimensional reconstruction of the fluorophore
      distribution from angle-resolved image stacks results in topographical
      information with an axial resolution of tens of nanometers. We applied this
      technique to study the axial position of dye-labeled subcellular storage
      organelles ('vesicles') of approximately 300 nm diameter in the "footprint"
      region of living neuroendocrine cells grown on the interface.

PMID- 10938763
TI  - Novel dental dynamic depth profilometric imaging using simultaneous frequency
      domain infrared photothermal radiometry and laser luminescence.
AB  - A high-spatial-resolution dynamic experimental imaging setup, which can provide
      simultaneous measurements of laser-induced frequency-domain infrared photothermal
      radiometric and luminescence signals from defects in teeth, has been developed
      for the first time. The major findings of this work are (i) radiometric images
      are complementary to (anticorrelated with) luminescence images, as a result of
      the nature of the two physical signal generation processes; (ii) the radiometric
      amplitude exhibits much superior dynamic (signal resolution) range to
      luminescence in distinguishing between intact and cracked sub-surface structures
      in the enamel; (iii) the radiometric signal (amplitude and phase) produces dental
      images with much better defect localization, delineation, and resolution; (iv)
      radiometric images (amplitude and phase) at a fixed modulation frequency are
      depth profilometric, whereas luminescence images are not; and (v) luminescence
      frequency responses from enamel and hydroxyapatite exhibit two relaxation
      lifetimes, the longer of which (approximately ms) is common to all and is not
      sensitive to the defect state and overall quality of the enamel. Simultaneous
      radiometric and luminescence frequency scans for the purpose of depth profiling
      were performed and a quantitative theoretical two-lifetime rate model of dental
      luminescence was advanced.

PMID- 10938764
TI  - Cell viability in optical tweezers: high power red laser diode versus Nd:YAG
      laser.
AB  - Viability of cultivated Chinese hamster ovary cells in optical tweezers was
      measured after exposure to various light doses of red high power laser diodes
      (lambda = 670-680 nm) and a Nd:yttrium-aluminum-garnet laser (lambda = 1064 nm).
      When using a radiant exposure of 2.4 GJ/cm2, a reduction of colony formation up
      to a factor 2 (670-680 nm) or 1.6 (1064 nm) as well as a delay of cell growth
      were detected in comparison with nonirradiated controls. In contrast, no cell
      damage was found at an exposure of 340 MJ/cm2 for both wavelengths, and virtually
      no lethal damage at 1 GJ/cm2 applied at 1064 nm. Cell viabilities were correlated
      with fluorescence excitation spectra and with literature data of wavelength
      dependent cloning efficiencies. Fluorescence excitation maxima of the coenzymes
      NAD(P)H and flavins were detected at 365 and 450 nm, respectively. This is half
      of the wavelengths of the maxima of cell inactivation, suggesting that two-photon
      absorption by these coenzymes may contribute to cellular damage. Two-photon
      excitation of NAD(P)H and flavins may also affect cell viability after exposure
      to 670-680 nm, whereas one-photon excitation of water molecules seems to limit
      cell viability at 1064 nm.

PMID- 10938765
TI  - First in-vivo trials of a fiber Bragg grating based temperature profiling system.
AB  - We describe the results of in-vivo trials of a portable fiber Bragg grating based
      temperature profile monitoring system. The probe incorporates five Bragg gratings
      along a single fiber and prevents the gratings from being strained. Illumination
      is provided by a superluminescent diode, and a miniature CCD based spectrometer
      is used for demultiplexing. The CCD signal is read into a portable computer
      through a small A/D interface; the computer then calculates the positions of the
      center wavelengths of the Bragg gratings, providing a resolution of 0.2 degree C.
      Tests were carried out on rabbits undergoing hyperthermia treatment of the kidney
      and liver via inductive heating of metallic implants and comparison was made with
      a commercial Fluoroptic thermometry system.

PMID- 10938766
TI  - Blood plasma coagulation studied by surface plasmon resonance.
AB  - A surface plasmon resonance (SPR) apparatus was used to investigate blood plasma
      coagulation in real time as a function of thromboplastin and heparin
      concentrations. The response curves were analyzed by curve fitting to a sigmoid
      curve equation, followed by extraction of the time constant. Clotting activation
      by thromboplastin resulted in increased time constant, as compared to
      spontaneously clotted plasma, in a dose dependent way. Addition of heparin to the
      thromboplastin-activated plasma counteracted this effect. Atomic force microscopy
      (AFM) pictures of sensor surfaces dried after completed clotting, revealed
      differences in fibrin network structures as a function of thromboplastin
      concentration, and the fiber thickness increased with decreased thromboplastin
      concentration. The physical reason for the SPR signal observed is ambiguous and
      is therefore discussed. However, the results summarized in the plots and the
      fibrin network properties observed by AFM correlate well with present common
      methods used to analyze blood coagulation.

PMID- 10938767
TI  - Initial in vivo results of a hybrid retinal photocoagulation system.
AB  - We describe initial in vivo experimental results of a new hybrid digital and
      analog design for retinal tracking and laser beam control. An overview of the
      design is given. The results show in vivo tracking rates which exceed the
      equivalent of 38 degrees/s in the eye. A robotically assisted lesion pattern is
      created for laser surgery to treat conditions such as diabetic retinopathy and
      retinal breaks.

PMID- 10938768
TI  - High resolution imaged laser speckle strain gauge for vascular applications.
AB  - An imaged laser speckle strain gauge that yields strain rates directly is
      described for vascular applications. The strain gauge does not rely upon cross
      correlations between a reference image and subsequent strain-modulated images as
      most current speckle interferometric methods do. Instead, it relies upon a two
      dimensional frequency transform of "stacked speckle histories" which are time
      series of one-dimensional views of the speckle patterns arranged into a spatio
      temporal array such that space is along the abscissa and time is along the
      ordinate. The tilt of the stacked speckle histories is related to the time rate
      of speckle pattern shift. The strain gauge is sensitive only to in-plane strains.
      Strain rates of 30.1 +/- 3.2 and 24.83 +/- 2.1 mu epsilon/s were evaluated in
      vitro on a fresh human tibial artery and rat inferior vena cava, respectively.
      The total strains measured were 21.6 and 19.86 mu epsilon, respectively. This is
      at least one order of magnitude more sensitive than other current soft-tissue
      strain measurement techniques.

PMID- 10938769
TI  - Image analysis for discrimination of cervical neoplasia.
AB  - Colposcopy involves visual imaging of the cervix for patients who have exhibited
      some prior indication of abnormality, and the major goals are to visually inspect
      for any malignancies and to guide biopsy sampling. Currently colposcopy equipment
      is being upgraded in many health care centers to incorporate digital image
      acquisition and archiving. These permanent images can be analyzed for
      characteristic features and color patterns which may enhance the specificity and
      objectivity of the routine exam. In this study a series of images from patients
      with biopsy confirmed cervical intraepithelia neoplasia stage 2/3 are compared
      with images from patients with biopsy confirmed immature squamous metaplasia,
      with the goal of determining optimal criteria for automated discrimination
      between them. All images were separated into their red, green, and blue channels,
      and comparisons were made between relative intensity, intensity variation,
      spatial frequencies, fractal dimension, and Euler number. This study indicates
      that computer-based processing of cervical images can provide some discrimination
      of the type of tissue features which are important for clinical evaluation, with
      the Euler number being the most clinically useful feature to discriminate
      metaplasia from neoplasia. Also there was a strong indication that morphology
      observed in the blue channel of the image provided more information about
      epithelial cell changes. Further research in this field can lead to advances in
      computer-aided diagnosis as well as the potential for online image enhancement in
      digital colposcopy.

PMID- 10938770
TI  - Spatially confined and temporally resolved refractive index and scattering
      evaluation in human skin performed with optical coherence tomography.
AB  - In the present applications of optical coherence tomography (OCT), parameters
      besides pure morphology are evaluated in skin tissue under in vivo conditions.
      Spatially mapped refractive indices and scattering coefficients may support
      tissue characterization for research and diagnostic purposes in
      cosmetics/pharmacy and medicine, respectively. The sample arm of our OCT setup
      has been arranged to permit refractive index evaluation with little mechanical
      adjustment of a lens within the objective. A simple algorithm has been derived.
      Known from atmospheric work, the Klett algorithm [J. D. Klett, "Stable analytical
      inversion solution for processing LIDAR returns," Appl. Opt. 20(2), 211-220
      (1981)] has been applied to the same data set for retrieval of scattering
      coefficients. Both parameters have been measured in layered structures in skin
      like stratum corneum, epidermis and dermis. Significant water content in a
      localized sweat gland duct has been observed by refractive index evaluation. Time
      studies over 1.5 h permitted a first understanding about physiological changes in
      skin which are not obtainable by intrusive methods.

PMID- 10938771
TI  - Activation of the visual cortex imaged by 24-channel near-infrared spectroscopy.
AB  - Near-infrared spectroscopy (NIRS) is a noninvasive technique for continuous
      monitoring of the amounts of total hemoglobin (total-Hb), oxygenated hemoglobin,
      (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb). The purpose of the present study
      was to demonstrate the utility of NIRS in functional imaging of the human visual
      cortex. A new NIRS imaging system enabled measurements from 24 scalp locations
      covering a 9 cm sq area. Topographic images were obtained from interpolations of
      the concentration changes between measurement points. Five healthy subjects
      between 25 and 49 years of age were investigated. After a resting baseline period
      of 50 s, the subjects were exposed to a visual stimulus for 20 s, followed by a
      50 s resting period in a dimly lit, sound attenuating room. The visual stimulus
      was a circular, black and white, alternating checkerboard. In four of five
      subjects the visual cortex was the most activated area during visual stimulation.
      This is the first reported use of a NIRS-imaging system for assessing hemodynamic
      changes in the human visual cortex. The typical hemodynamic changes expected were
      observed; the total-Hb and oxy-Hb increased just after the start of stimulation
      and plateaued after 10 s of the stimulation period.

PMID- 10938772
TI  - Oxygen supply-consumption balance in the thigh muscles during exhausting knee
      extension exercise.
AB  - The purpose of this study was to investigate the difference in muscle oxygenation
      between the individual muscles involved in an exhaustive knee-extension exercise.
      Eight active women performed exercise by extending the knee joint from 90 degrees
      to 30 degrees (60 extensions min-1) at 20%, 30%, and 40% maximum voluntary
      contraction (MVC). Changes in oxy-(delta HbO2), deoxy-(delta Hb), and total
      (delta HbT) hemoglobin concentrations, and oxygen saturation (delta SO2NIRS =
      HbO2/HbT) in the vastus lateralis (VL) and rectus femoris (RF) muscles were
      measured with a spatially resolved near-infrared spectrometer (NIRS). The delta
      SO2NIRS in the VL and RF decreased rapidly from the pre-exercise control value
      (VL: 75.6 +/- 0.9%; RF: 81.6 +/- 1.6%) at the onset of exercise at three
      different intensities, although no significant difference in delta SO2NIRS was
      found between the two muscles at this time. However, the delta SO2NIRS decreased
      more rapidly thereafter and reached a lower value at exhaustion in the VL than in
      the RF. The difference in delta SO2NIRS between the VL (-10.3 +/- 1.7%) and RF (
      4.0 +/- 1.0%) was significant (p < 0.05) when exercise intensity was 30% MVC.
      When the decreases in delta HbO2 and delta HbT (p < 0.05) were compared at
      different exercise intensities, the values at 30% and 40% MVC were significantly
      lower (delta HbO2: p < 0.01; delta HbT: p < 0.05) than those at 20% MVC in the
      VL, but there was no significant difference in any of the parameters in the RF,
      or in delta Hb in the VL. These results suggest that the muscle oxidative
      response to exhaustive knee-extension exercise differed between the VL and RF
      muscles. At exhaustion, oxygen saturation decreased to a lower level in the VL
      than in the RF, and an intensity-dependent difference in muscle oxygenation
      parameters was observed at 30% MVC in the VL but not in the RF muscles.

PMID- 10938773
TI  - Quantification of ischemic muscle deoxygenation by near infrared time-resolved
      spectroscopy.
AB  - The purpose of this study was to quantify muscle deoxygenation in human skeletal
      muscles using near infrared time-resolved spectroscopy (NIRTRS) and compare
      NIRTRS indicators and blood saturation. The forearm muscles of five healthy males
      (aged 27-32 yrs.) were monitored for changes in hemoglobin saturation (SO2)
      during 12 min of arterial occlusion and recovery. SO2 was determined by measuring
      the temporal profile of photon diffusion at 780 and 830 nm using NIRTRS, and was
      defined as SO2-TRS. Venous blood samples were also obtained for measurements of
      SvO2, and PvO2. Interstitial PO2(PintO2) was monitored by placing an O2 electrode
      directly into the muscle tissue. Upon the initiation of occlusion, all parameters
      fell progressively until reaching a plateau in the latter half of occlusion. It
      was observed at the end of occlusion that SO2-TRS (24.1 +/- 5.6%) agreed with
      SvO2 (26.2 +/- 6.4) and that PintO2 (14.7 +/- 1.0 Torr) agreed with PvO2 (17.3 +/
      2.2 Torr). The resting O2 store (oxygenated hemoglobin) and O2 consumption rate
      were 290 microM and 0.82 microM s-1, respectively, values which reasonably agree
      with the reported results. These results indicate that there was no O2 gradient
      between vessels and interstisium at the end of occlusion.

PMID- 10938774
TI  - Celebrating Britton Chance.

PMID- 10938775
TI  - Principles and pitfalls of diagnostic test development: implications for
      spectroscopic tissue diagnosis.
AB  - Diagnostic spectroscopy has the potential to supplant the time-honored "gold
      standard" of light microscopy and herald an era of in vivo tissue diagnosis.
      However, the lessons in disease diagnosis learned by pathologists over the years
      should not be forgotten. This discussion will focus on the basis principles and
      pitfalls of diagnostic test development, and how they apply to optical
      spectroscopy tissue diagnosis.

PMID- 10938777
TI  - Feasibility of field-based light scattering spectroscopy.
AB  - Light scattering spectroscopy (LSS) is a new technique capable of accurately
      measuring the features of nuclei and other cellular organelles in situ. We
      present the considerations required to implement and interpret field-based
      detection in LSS, where the scattered electric field is detected
      interferometrically, and demonstrate that the technique is experimentally
      feasible. A theoretical formalism for modeling field-based LSS signals based on
      Mie scattering is presented. Phase-front uniformity is shown to play an important
      and novel role. Results of heterodyne experiments with polystyrene microspheres
      that localize LSS signals to a region about 30 microns in axial extent are
      reported. In addition, differences between field-based LSS and the earlier
      intensity-based LSS are discussed.

PMID- 10938776
TI  - Light scattering from cells: the contribution of the nucleus and the effects of
      proliferative status.
AB  - As part of our ongoing efforts to understand the fundamental nature of light
      scattering from cells and tissues, we present data on elastic light scattering
      from isolated mammalian tumor cells and nuclei. The contribution of scattering
      from internal structures and in particular from the nuclei was compared to
      scattering from whole cells. Roughly 55% of the elastic light scattering at high
      angles (> 40 degrees) comes from intracellular structures. An upper limit of 40%
      on the fractional contribution of nuclei to scattering from cells in tissue was
      determined. Using cell suspensions isolated from monolayer cultures at different
      stages of growth, we have also found that scattering at angles greater than about
      110 degrees was correlated with the DNA content of the cells. Based on model
      calculations and the relative size difference of nuclei from cells in different
      stages of growth, we argue that this difference in scattering results from
      changes in the internal structures of the nucleus. This interpretation is
      consistent with our estimate of 0.2 micron as the mean size of the scattering
      centers in cells. Additionally, we find that while scattering from the nucleus
      accounts for a majority of internal scattering, a significant portion must result
      from scattering off of cytoplasmic structures such as mitochondria.

PMID- 10938778
TI  - Optical computed tomography in a turbid medium using early arriving photons.
AB  - We employ photon migration to image absorbing objects embedded in a turbid
      medium. For improved resolution, we use early arriving photons (a few hundred
      picoseconds in excess of the time of flight), a regime in which the diffusion
      approximation breaks down. Our image reconstruction method is based on extension
      of x-ray computed tomography (CT) to the optical regime. The CT algorithm must be
      generalized to take into account the distributions of photon paths. We express
      the point spread function (PSF) in terms of the Green's function for the
      transport equation. This PSF then provides weighting functions for use in a
      generalized series expansion method of x-ray CT. Experiments were performed on a
      turbid medium with scattering and absorption properties similar to those of human
      breast tissue. Multiple absorbers were embedded into the medium to mimic tumors.
      Coaxial transmission scans were collected in two projections, and the early-time
      portions were analyzed. Through accurate modeling, we could remove the blurring
      associated with multiple scattering and obtain high-resolution images. Our
      results show that the diffusion approximation PSF is inadequate to describe the
      early arriving photons. A PSF incorporating causality is required to reconstruct
      accurate images of turbid media.

PMID- 10938779
TI  - Measurement of oxygen saturation in venous blood by dynamic near infrared
      spectroscopy.
AB  - A method for the measurement of oxygen saturation in the venous blood, SvO2,
      based on optical measurements of light absorption in the infrared region is
      presented. The method consists of applying relatively low external pressure of 25
      mm Hg on the forearm, thereby increasing the venous blood volume in the tissue,
      and comparing the light absorption before and after the external pressure
      application. SvO2 has been determined from light absorption measurements in two
      wavelengths, before and after the pressure application, using a formula derived
      for two adjacent wavelengths. The method has been applied to the hands and
      fingers of 17 healthy male subjects, using wavelengths of 767 and 811 nm. SaO2,
      the oxygen saturation for arterial blood, was also obtained from
      photoplethysmographic measurements in these two wavelengths (pulse oximetry)
      using the same formula. The mean (+/- SD) value of SaO2 was 94.5% (+/- 3.0). The
      mean value of SvO2 was 86.2% (+/- 4.1) for the finger and 80.0% (+/- 8.2) for the
      hand. These SvO2 values are reasonable for the finger and the hand where arterio
      venous anastomoses exist. The method enables the measurement of SvO2 in the
      limbs, a parameter which is related to tissue blood flow and oxygen consumption.

PMID- 10938780
TI  - Photon migration through fetal head in utero using continuous wave, near-infrared
      spectroscopy: development and evaluation of experimental and numerical models.
AB  - In this work experimental tissue phantoms and numerical models were developed to
      estimate photon migration through the fetal head in utero. The tissue phantoms
      incorporate a fetal head within an amniotic fluid sac surrounded by a maternal
      tissue layer. A continuous wave, dual-wavelength (lambda = 760 and 850 nm)
      spectrometer was employed to make near-infrared measurements on the tissue
      phantoms for various source-detector separations, fetal-head positions, and fetal
      head optical properties. In addition, numerical simulations of photon propagation
      were performed with finite-difference algorithms that provide solutions to the
      equation of radiative transfer as well as the diffusion equation. The simulations
      were compared with measurements on tissue phantoms to determine the best
      numerical model to describe photon migration through the fetal head in utero.
      Evaluation of the results indicates that tissue phantoms in which the contact
      between fetal head and uterine wall is uniform best simulates the fetal head in
      utero for near-term pregnancies. Furthermore, we found that maximum sensitivity
      to the head can be achieved if the source of the probe is positioned directly
      above the fetal head. By optimizing the source-detector separation, the signal
      originating from photons that have traveled through the fetal head can
      drastically be increased.

PMID- 10938781
TI  - Photon migration through fetal head in utero using continuous wave, near infrared
      spectroscopy: clinical and experimental model studies.
AB  - Near infrared (NIR) measurements were made from the maternal abdomen (clinical
      studies) and laboratory tissue phantoms (experimental studies) to gain insight
      into photon migration through the fetal head in utero. Specifically, a continuous
      wave spectrometer was modified and employed to make NIR measurements at 760 and
      850 nm, at a large (10 cm) and small (2.5/4 cm) source-detector separation,
      simultaneously, on the maternal abdomen, directly above the fetal head. A total
      of 19 patients were evaluated, whose average gestational age and fetal head
      depth, were 37 weeks +/- 3 and 2.25 cm +/- 0.7, respectively. At the large source
      detector separation, the photons are expected to migrate through both the
      underlying maternal and fetal tissues before being detected at the surface, while
      at the short source-detector separation, the photons are expected to migrate
      primarily through the superficial maternal tissues before being detected. Second,
      similar NIR measurements were made on laboratory tissue phantoms, with variable
      optical properties and physical geometries. The variable optical properties were
      obtained using different concentrations of India ink and Intralipid in water,
      while the variable physical geometries were realized by employing glass
      containers of different shapes and sizes. Third, the NIR measurements, which were
      made on the laboratory tissue phantoms, were compared to the NIR measurements
      made on the maternal abdomen to determine which tissue phantom best simulates the
      photon migration path through the fetal head in utero. The results of the
      comparison were used to provide insight into the optical properties and physical
      geometry of the maternal and fetal tissues in the photon migration path.

PMID- 10938782
TI  - Calibration of near-infrared frequency-domain tissue spectroscopy for absolute
      absorption coefficient quantitation in neonatal head-simulating phantoms.
AB  - Frequency-domain tissue spectroscopy is a method to measure the absolute
      absorption coefficient of bulk tissues, assuming that a representative model can
      be found to recover the optical properties from measurements. While reliable
      methods exist to calculate absorption coefficients from source-detector
      measurements less than a few centimeters apart along a flat tissue volume, it is
      less obvious what methods can be used for transmittance through the larger tissue
      volumes typically associated with neonatal cerebral monitoring. In this study we
      compare the use of multiple distance frequency-domain measurements processed with
      (i) a modified Beer-Lambert law method, (ii) an analytic infinite-medium
      diffusion theory expression, and (iii) a numerical finite element solution of the
      diffusion equation, with the goal of recovering the absolute absorption
      coefficient of the medium. Based upon our observations, the modified Beer-Lambert
      method provides accurate absolute changes in the absorption coefficient, while
      analytic infinite-medium diffusion theory solutions or finite element-based
      numerical solutions can be used to calculate the absolute absorption coefficient,
      assuming that the data can be measured at multiple source-detector distances. We
      recommend that the infinite-medium multi-distance method or the finite element
      method be used across large tissue regions for calculation of the absolute
      absorption coefficient using frequency-domain near-infrared measurements at
      multiple positions along the head.

PMID- 10938783
TI  - Preliminary evaluation of dual wavelength phased array imaging on neonatal brain
      function.
AB  - Imaging of human tissue using noninvasive techniques has been of great interest
      in biomedical fields. Optical imaging has attracted a lot of attention because of
      its portability and economy. The possibility that a highly portable, fast, safe,
      and affordable imaging system which could obtain interpretable images of brain
      function for pre- and full-term neonates in a few seconds, has been explored in
      this article. We have used a sensitive optical topography system, termed phased
      array, in which a pair of equal-amplitude and antiphase light sources are applied
      to generate a sharp amplitude null and phase transition plane. This two
      wavelength (750 and 830 nm), frequency encoded (50 and 52 MHz) phased array
      imaging system can indicate the blood concentration and oxygenation changes in
      blood model studies and during parietal brain activation in neonates. Significant
      functional responses, particularly to parietal stimulation in normal and
      pathological states of neonatal brain, have been revealed in our study. The
      preliminary clinical results are presented in this article.

PMID- 10938784
TI  - Noninvasive measurement of cerebral hemoglobin oxygen saturation using two near
      infrared spectroscopy approaches.
AB  - Spatially resolved spectroscopy (SRS) is a new near infrared spectroscopy (NIRS)
      method that, using the multi-distance approach, measures local cerebral cortex
      hemoglobin oxygen saturation [J. Matcher, P. Kirkpatrick, K. Nahid, M. Cope, and
      D. T. Delpy, Proc. SPIE 2389, 486-495 (1995)]. Using a conventional continuous
      wave NIRS photometer, cerebral venous oxygen saturation (SvO2) can be calculated
      from oxyhemoglobin and total hemoglobin rise induced by partial occlusion of
      jugular vein [C. E. Elwell, S. J. Matcher, L. Tyszczuk, J. H. Meek, and D. T.
      Delpy, Adv. Exp. Med. Biol. 411, 453-460 (1997)]. The aim of this study was to
      compare direct measurements of forehead tissue oxygenation index (TOI) with the
      calculated SvO2 during venous occlusion in 16 adult volunteers using a clinical
      two-channel SRS oximeter (NIRO-300). Measured TOI and calculated SvO2 values of
      either right or left forehead did not significantly differ. A good agreement
      between the two NIRS methods was also demonstrated. On 16 other subjects, no
      significant differences were found between the right and left forehead TOI values
      measured simultaneously, and between the TOI values measured by channel 1 or 2 on
      the same side. The results confirm that cerebral cortex hemoglobin oxygen
      saturation, measured directly by the SRS method, reflects predominantly the
      saturation of the intracranial venous compartment of circulation.

PMID- 10938785
TI  - Study of near infrared technology for intracranial hematoma detection.
AB  - Although intracranial hematoma detection only requires the continuous wave
      technique of near infrared spectroscopy (NIRS), previous studies have shown that
      there are still some problems in obtaining very accurate, reliable hematoma
      detection. Several of the most important limitations of NIR technology for
      hematoma detection such as the dynamic range of detection, hair absorption,
      optical contact, layered structure of the head, and depth of detection are
      reported in this article. A pulsed light source of variable intensity was
      designed and studied in order to overcome hair absorption and to increase the
      dynamic range and depth of detection. An adaptive elastic optical probe was made
      to improve the optical contact and decrease contact noise. A new microcontroller
      operated portable hematoma detector was developed. Due to the layered structure
      of the human head, simulation on a layered medium was analyzed experimentally.
      Model inhomogeneity tests and animal hematoma tests showed the effectiveness of
      the improved hematoma detector for intracranial hematoma detection.

PMID- 10938786
TI  - Brain tumor demarcation using optical spectroscopy; an in vitro study.
AB  - Optical spectroscopy for brain tumor demarcation was investigated in this study.
      Fluorescence and diffuse reflectance spectra were measured from normal and
      tumorous human brain tissues in vitro. A fluorescence peak was consistently
      observed around 460 nm (+/- 10 nm) emission from both normal and tumorous brain
      tissues using 337 nm excitation. Intensity of this fluorescence peak (F460) from
      normal brain tissues was greater than that from primary brain tumorous tissues.
      In addition, diffuse reflectance (Rd) between 650 and 800 nm from white matter
      was significantly stronger than that from primary and secondary brain tumors. A
      good separation between gray matter and brain tumors was found using the ratio of
      F460 and Rd at 460 nm (Rd460). Two empirical discrimination algorithms based on
      F460, Rd625, and F460/Rd460 were developed. These algorithms yielded an average
      sensitivity and specificity of 96% and 93%, respectively.

PMID- 10938787
TI  - Diagnosis of breast cancer using elastic-scattering spectroscopy: preliminary
      clinical results.
AB  - We report on the first stages of a clinical study designed to test elastic
      scattering spectroscopy, mediated by fiberoptic probes, for three specific
      clinical applications in breast-tissue diagnosis: (1) a transdermal-needle
      (interstitial) measurement for instant diagnosis with minimal invasiveness
      similar to fine-needle aspiration but with sensitivity to a larger tissue volume,
      (2) a hand-held diagnostic probe for use in assessing tumor/resection margins
      during open surgery, and (3) use of the same probe for real-time assessment of
      the "sentinel" node during surgery to determine the presence or absence of tumor
      (metastatic). Preliminary results from in vivo measurements on 31 women are
      encouraging. Optical spectra were measured on 72 histology sites in breast
      tissue, and 54 histology sites in sentinel nodes. Two different artificial
      intelligence methods of spectral classification were studied. Artificial neural
      networks yielded sensitivities of 69% and 58%, and specificities of 85% and 93%,
      for breast tissue and sentinel nodes, respectively. Hierarchical cluster analysis
      yielded sensitivities of 67% and 91%, and specificities of 79% and 77%, for
      breast tissue and sentinel nodes, respectively. These values are expected to
      improve as the data sets continue to grow and more sophisticated data
      preprocessing is employed. The study will enroll up to 400 patients over the next
      two years.

PMID- 10938788
TI  - Optical imaging as an adjunct to sonograph in differentiating benign from
      malignant breast lesions.
AB  - The role of near infrared (NIR) diffusive light imaging as an adjunct to
      ultrasound in differentiating benign from malignant lesions was evaluated in 27
      mammography patients with infiltrating ductal carcinomas, apocrine metaplasia,
      fibroadenomas, radial scar and ductal hyperplasia, cysts, and normal tissues.
      Conventional ultrasound/mammography images were graded based on BI-RADS
      assessment categories. The spatial NIR measurements were made at wavelengths of
      750 and 830 nm. Functional images, such as relative changes of deoxyhemoglobin
      (deoxyHb) and total blood concentration, were estimated from the dual wavelength
      measurements. Maximum relative deoxyHb and blood concentration changes were
      measured, and spatial correlation of masses in relative deoxyHb and blood
      concentration images for each breast were calculated. For the five biopsy proven
      benign lesions, ultrasound/mammography diagnoses were suspicious for malignancy
      (four cases) and highly suspicious for malignancy (one case). Four lesions showed
      less than 1.0 V maximum deoxyHb and less than 1.5 V maximum blood concentration
      levels on average and spatial image correlation showed no correlated masses in
      both deoxyHb and blood concentration images. For the four biopsy proven malignant
      lesions, ultrasound/mammography diagnoses were highly suspicious for malignancy.
      Maximum deoxyHb and blood concentration changes were greater than 2.9 V on
      average except one lesion which showed smaller deoxyHb signal (maximum 0.85 V)
      but the deoxyHb mass and blood concentration mass were highly correlated.

PMID- 10938790
TI  - Crop improvement in the 21st century.
AB  - Crop yields increased dramatically in the 20th century as recorded on Broadbalk
      or in world averages. The vast majority of that increase has occurred since the
      last world war and has been powered by changes in the genetic potential of the
      crop and in the way in which it has been managed. Nevertheless, the challenge to
      feed a world population that is likely to rise to 8 billion is formidable,
      particularly since recent analyses suggest that the rate of increase in yields of
      several crops may have dropped over the last decade. What are the opportunities
      to meet this challenge and to continue to improve the yields of our crops?
      Improvements in agronomy are likely to be more concerned with efficiency and
      elegance rather than in major breakthroughs. More sophisticated crop protection
      chemicals designed on the basis of vastly increased screening potentials and (at
      last?) possibilities of rational design will be supplemented by a battery of
      decision support systems to aid management choices which can be precisely
      implemented. Genetic improvement is the area in which to-look for the major
      breakthroughs. The broad potential of recombinant DNA technology will provide the
      possibility of both molecular analyses of crop productivity and ways in which it
      may be possible to improve that productivity. The goal of analysis may be
      approached in three ways: starting at the beginning by generating complete
      sequences of the plant genome; starting at the end by genetic analysis of
      phenotypes using genetic marker technology; or, starting in the middle, by
      metabolic analysis. Improvements may be obtained by re-assorting what has been
      achieved through enhanced breeding technologies, by randomly induced change, and
      by generation of totally new possibilities through biochemical engineering.
      Examples of all approaches will be given. The onset of genomics will provide
      massive amounts of information, but the success will depend on using that to
      improve crop phenotypes. The ability to meet the challenges of the 21st century
      will depend on the ability to close that 'phenotype gap'.

PMID- 10938789
TI  - Three-dimensional diffuse optical mammography with ultrasound localization in a
      human subject.
AB  - We describe an approach that combines clinical ultrasound and photon migration
      techniques to enhance the sensitivity and information content of diffuse optical
      tomography. Measurements were performed on a postmenopausal woman with a single
      1.8 x 0.9 cm malignant ductal carcinoma in situ approximately 7.4 mm beneath the
      skin surface (UCI IRB protocol 95-563). The ultrasound-derived information about
      tumor geometry enabled us to segment the breast tissue into tumor and background
      regions. Optical data was obtained with a multifrequency, multiwavelength hand
      held frequency-domain photon migration backscattering probe. The optical
      properties of the tumor and background were then computed using the ultrasound
      derived geometrical constraints. An iterative perturbative approach, using
      parallel processing, provided quantitative information about scattering and
      absorption simultaneously with the ability to incorporate and resolve complex
      boundary conditions and geometries. A three to four fold increase in the tumor
      absorption coefficient and nearly 50% reduction in scattering coefficient
      relative to background was observed (lambda = 674, 782, 803, and 849 nm).
      Calculations of the mean physiological parameters reveal fourfold greater tumor
      total hemoglobin concentration [Hbtot] than normal breast (67 microM vs 16
      microM) and tumor hemoglobin oxygen saturation (SOx) values of 63% (vs 73% and
      68% in the region surrounding the tumor and the opposite normal tissue,
      respectively). Comparison of semi-infinite to heterogeneous models shows superior
      tumor/background contrast for the latter in both absorption and scattering.
      Sensitivity studies assessing the impact of tumor size and refractive index
      assumptions, as well as scan direction, demonstrate modest effects on recovered
      properties.

PMID- 10938791
TI  - Wild barley: a source of genes for crop improvement in the 21st century?
AB  - The development of new barleys tolerant of abiotic and biotic stresses is an
      essential part of the continued improvement of the crop. The domestication of
      barley, as in many crops, resulted in a marked truncation of the genetical
      variation present in wild populations. This process is significant to agronomists
      and scientists because a lack of allelic variation will prevent the development
      of adapted cultivars and hinder the investigation of the genetic mechanisms
      underlying performance. Wild barley would be a useful source of new genetic
      variation for abiotic stress tolerance if surveys identify appropriate genetic
      variation and the development of marker-assisted selection allows efficient
      manipulation in cultivar development. There are many wild barley collections from
      all areas of its natural distribution, but the largest are derived from the
      Mediterranean region. The results of a range of assays designed to explore
      abiotic stress tolerance in barley are reported in this paper. The assays
      included; sodium chloride uptake in wild barley and a mapping population, effects
      for delta 13C and plant dry weight in wheat aneuploids, effects of photoperiod
      and vernalization in wild barley, and measurements of root length in wild barley
      given drought and nitrogen starvation treatments in hydroponic culture. There are
      examples of the use of wild barley in breeding programmes, for example, as a
      source of new disease resistance genes, but the further exploration of the
      differences between wild barley and cultivars is hampered by the lack of good
      genetic maps. In parallel to the need for genetic studies there is also a need
      for the development of good physiological models of crop responses to the
      environment. Given these tools, wild barley offers the prospect of a 'goldmine'
      of untapped genetic reserves.

PMID- 10938792
TI  - The development and application of molecular markers for abiotic stress tolerance
      in barley.
AB  - This article represents some current thinking and objectives in the use of
      molecular markers to abiotic stress tolerance. Barley has been chosen for study
      as it is an important crop species, as well as a model for genetic and
      physiological studies. It is an important crop and, because of its well-studied
      genetics and physiology, is an excellent candidate in which to devise more
      efficient breeding methods. Abiotic stress work on cultivated gene pools of small
      grain cereals frequently shows that adaptive and developmental genes are strongly
      associated with responses. Developmental genes have strong pleiotropic effects on
      a number of performance traits, not just abiotic stresses. One concern is that
      much of the genetic variation for improving abiotic stress tolerance has been
      lost during domestication, selection and modern breeding, leaving pleiotropic
      effects of the selected genes for development and adaptation. Such genes are
      critical in matching cultivars to their target agronomic environment, and since
      there is little leverage in changing these, other sources of variation may be
      required. In barley, and many other crops, greater variation to abiotic stresses
      exists in primitive landraces and related wild species gene pools. Wild barley,
      Hordeum spontaneum C. Koch is the progenitor of cultivated barley, Hordeum
      vulgare L. and is easily hybridized to H. vulgare. Genetic fingerprinting of H.
      spontaneum has revealed genetic marker associations with site-of-origin
      ecogeographic factors and also experimentally imposed stresses. Genotypes and
      collection sites have been identified which show the desired variation for
      particular stresses. Doubled haploid and other segregating populations, including
      landrace derivatives have been used to map genetically the loci involved. These
      data can be used in molecular breeding approaches to improve the drought
      tolerance of barley. One strategy involves screening for genetic markers and
      physiological traits for drought tolerance, and the associated problem of drought
      relief-induced mildew susceptibility in naturally droughted fields of North
      Africa.

PMID- 10938793
TI  - Decreased NADH glutamate synthase activity in nodules and flowers of alfalfa
      (Medicago sativa L.) transformed with an antisense glutamate synthase transgene.
AB  - Legumes obtain a substantial portion of their nitrogen (N) from symbiotic N2
      fixation in root nodules. The glutamine synthetase (GS, EC 6.3.1.2)/glutamate
      synthase (GOGAT) cycle is responsible for the initial N assimilation. This report
      describes the analysis of a transgenic alfalfa (Medicago sativa L.) line
      containing an antisense NADH-GOGAT (EC 1.4.1.14) under the control of the nodule
      enhanced aspartate amino-transferase (AAT-2) promoter. In one transgenic line,
      NADH-GOGAT enzyme activity was reduced to approximately 50%, with a corresponding
      reduction in protein and mRNA. The transcript abundance for cytosolic GS,
      ferredoxin-dependent GOGAT (EC 1.4.7.1), AAT-2 (EC 2.6.1.1), asparagine synthase
      (EC 6.3.5.4), and phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) were
      unaffected, as were enzyme activities for AAT, PEPC and GS. Antisense NADH-GOGAT
      plants grown under symbiotic conditions were moderately chlorotic and reduced in
      growth and N content, even though symbiotic N2 fixation was not significantly
      reduced. The addition of nitrate relieved the chlorosis and restored growth and N
      content. Surprisingly, the antisense NADH-GOGAT plants were male sterile
      resulting from inviable pollen. A reduction in NADH-GOGAT enzyme activity and
      transcript abundance in the antisense plants was measured during the early stages
      of flower development. Inheritance of the transgene was stable and resulted in
      progeny with a range of NADH-GOGAT activity. These data indicate that NADH-GOGAT
      plays a critical role in the assimilation of symbiotically fixed N and during
      pollen development.

PMID- 10938794
TI  - Using stable isotope natural abundances (delta 15N and delta 13C) to integrate
      the stress responses of wild barley (Hordeum spontaneum C. Koch.) genotypes.
AB  - To integrate the complex physiological responses of plants to stress, natural
      abundances (delta) of the stable isotope pairs 15N/14N and 13C/12C were measured
      in 30 genotypes of wild barley (Hordeum spontaneum C. Koch.). These accessions,
      originating from ecologically diverse sites, were grown in a controlled
      environment and subjected to mild, short-term drought or N-starvation. Increases
      in total dry weight were paralleled by less negative delta 13C in shoots and, in
      unstressed and droughted plants, by less negative whole-plant delta 13C. Root
      delta 15N was correlated negatively with total dry weight, whereas shoot and
      whole-plant delta 15N were not correlated with dry weight. The difference in
      delta 15N between shoot and root varied with stress in all genotypes. Shoot-root
      delta 15N may be a more sensitive indicator of stress response than shoot, root
      or whole-plant delta 15N alone. Among the potentially most productive genotypes,
      the most stress-tolerant had the most negative whole-plant delta 15N, whether the
      stress was drought or N-starvation. In common, controlled experiments, genotypic
      differences in whole-plant delta 15N may reflect the extent to which N can be
      retained within plants when stressed.

PMID- 10938795
TI  - Regulation of Arabidopsis root development by nitrate availability.
AB  - When the root systems of many plant species are exposed to a localized source of
      nitrate (NO3- they respond by proliferating their lateral roots to colonize the
      nutrient-rich zone. This study reviews recent work with Arabidopsis thaliana in
      which molecular genetic approaches are being used to try to understand the
      physiological and genetic basis for this response. These studies have led to the
      conclusion that there are two distinct pathways by which NO3- modulates root
      branching in Arabidopsis. On the one hand, meristematic activity in lateral root
      tips is stimulated by direct contact with an enriched source of NO3- (the
      localized stimulatory effect). On the other, a critical stage in the development
      of the lateral root (just after its emergence from the primary root) is highly
      susceptible to inhibition by a systemic signal that is related to the amount of
      NO3- absorbed by the plant (the systemic inhibitory effect). Evidence has been
      obtained that the localized stimulatory effect is a direct effect of the NO3- ion
      itself rather than a nutritional effect. A NO3(-)-inducible MADS-box gene (ANR1)
      has been identified which encodes a component of the signal transduction pathway
      linking the external NO3- supply to the increased rate of lateral root
      elongation. Experiments using auxin-resistant mutants have provided evidence for
      an overlap between the auxin and NO3- response pathways in the control of lateral
      root elongation. The systemic inhibitory effect, which does not affect lateral
      root initiation but delays the activation of the lateral root meristem, appears
      to be positively correlated with the N status of the plant and is postulated to
      involve a phloem-mediated signal from the shoot.

PMID- 10938796
TI  - Root hydraulic conductance: diurnal aquaporin expression and the effects of
      nutrient stress.
AB  - It has been shown that N-, P- and S-deficiencies result in major reductions of
      root hydraulic conductivity (Lpr) which may lead to lowered stomatal conductance,
      but the relationship between the two conductance changes is not understood. In a
      variety of species, Lpr decreases in the early stages of NO3-, H2PO4(2-) and
      SO4(2-) deprivation. These effects can be reversed in 4-24 h after the deficient
      nutrient is re-supplied. Diurnal fluctuations of root Lpr have also been found in
      some species, and an example of this is given for Lotus japonicus. In nutrient
      sufficient wheat plants, root Lpr is extremely sensitive to brief treatments with
      HgCl2; these effects are completely reversible when Hg is removed. The low values
      of Lpr in N- or P-deprived roots of wheat are not affected by Hg treatments. The
      properties of plasma membrane (PM) vesicles from wheat roots are also affected by
      NO3(-)-deprivation of the intact plants. The osmotic permeability of vesicles
      from N-deprived roots is much lower than that of roots adequately supplied with
      NO3-, and is insensitive to Hg treatment. In roots of L. japonicus, gene
      transcripts are found which have a strong homology to those encoding the PIP1 and
      PIP2 aquaporins of Arabidopsis. There is a very marked diurnal cycle in the
      abundance of mRNAs of aquaporin gene homologues in roots of L. japonicus. The
      maxima and minima appear to anticipate the diurnal fluctuations in Lpr by 2-4 h.
      The temporal similarity between the cycles of the abundance of the mRNAs and root
      Lpr is most striking. The aquaporin encoded by AtPIP1 is known to have its water
      permeation blocked by Hg binding. The lack of Hg-sensitivity in roots and PMs
      from N-deprived roots provides circumstantial evidence that lowered root Lpr may
      be due to a decrease in either the activity of water channels or their density in
      the PM. It is concluded that roots are capable, by means completely unknown, of
      monitoring the nutrient content of the solution in the root apoplasm and of
      initiating responses that anticipate by hours or days any metabolic disturbances
      caused by nutrient deficiencies. It is the incoming nutrient supply that is
      registered as deficient, not the plant's nutrient status. At some point, close to
      the initiation of these responses, changes in water channel activity may be
      involved, but the manner in which monitoring of nutrient stress is transduced
      into an hydraulic response is also unknown.

PMID- 10938797
TI  - Molecular physiology of zinc transport in the Zn hyperaccumulator Thlaspi
      caerulescens.
AB  - In this manuscript, recent research from this laboratory into physiological and
      molecular aspects of heavy metal (Zn) transport in the hyperaccumulating plant
      species, Thlaspi caerulescens is reviewed. This research is aimed at elucidating
      the processes that underlie the accumulation of extraordinarily high levels of Zn
      in the T. caerulescens shoot (up to 3% Zn dry wt.) without any associated
      toxicity symptom. Physiological studies focused on the use of radiotracer flux
      techniques (65Zn2+) to characterize zinc transport and compartmentation in the
      root, and translocation and accumulation in the shoot of T. caerulescens in
      comparison with a related non-accumulator, T. arvense. These studies indicated
      that Zn transport was stimulated at a number of sites in T. caerulescens,
      contributing to the hyperaccumulation trait. The transport processes that were
      stimulated included Zn influx into both root and leaf cells, and Zn loading into
      the xylem. The 4- to 5-fold stimulation of Zn influx into the root was
      hypothesized to be due to an increased abundance of Zn transporters in T.
      caerulescens root cells. Additionally, compartmental analysis (radiotracer wash
      out or efflux techniques) was used to show that Zn was sequestered in the
      vacuoles of T. arvense root cells which retarded Zn translocation to the shoot in
      this non-accumulator species. Molecular studies have focused on the cloning and
      characterization of Zn transport genes in T. caerulescens. Complementation of a
      yeast Zn transport-defective mutant with a T. caerulescens cDNA library resulted
      in the recovery of a cDNA, ZNT1, that encodes a Zn transporter. Sequence analysis
      of ZNT1 indicated it is a member of a recently discovered micronutrient transport
      gene family which includes the Arabidopsis Fe transporter, IRT1, and the ZIP Zn
      transporters. Expression of ZNT1 in yeast allowed for a physiological
      characterization of this transporter. It was shown to encode a high affinity Zn
      transporter which can also mediate low affinity Cd transport. Northern analysis
      of ZNT1 and its homologue in the two Thlaspi species indicated that enhanced Zn
      transport in T. caerulescens results from a constitutively high expression of the
      ZNT1 gene in roots and shoots. In T. arvense, ZNT1 is expressed at far lower
      levels and this expression is stimulated by imposition of Zn deficiency.

PMID- 10938798
TI  - Genetic engineering of glycinebetaine synthesis in plants: current status and
      implications for enhancement of stress tolerance.
AB  - Metabolic acclimation via the accumulation of compatible solutes is regarded as a
      basic strategy for the protection and survival of plants in extreme environments.
      Certain plants accumulate significant amounts of glycinebetaine (betaine), a
      compatible quaternary amine, in response to high salinity, cold and drought. It
      is likely that betaine is involved in the protection of macrocomponents of plant
      cells, such as protein complexes and membranes, under stress conditions. Genetic
      engineering of the biosynthesis of betaine from choline has been the focus of
      considerable attention as a potential strategy for increasing stress tolerance in
      stress-sensitive plants that are incapable of synthesizing this
      compatible/protective solute. Three distinct pathways for the synthesis of
      betaine have been identified in spinach, Escherichia coli and Arthrobacter
      globiformis, and various genes and cDNAs for the proteins involved are available.
      Moreover, each of the pathways has been exploited to a greater or lesser extent
      in efforts to convert betaine-deficient plants to betaine accumulators. In this
      review, the potential of several recent examples of transgenic approaches to the
      enhancement of stress tolerance in plants is summarized and discussed.

PMID- 10938799
TI  - Molecular strategies for improving waterlogging tolerance in plants.
AB  - Plants, like animals, are obligate aerobes, but due to their inability to move,
      have evolved adaptation mechanisms that enable them to survive short periods of
      low oxygen supply, such as those occurring after heavy rain or flooding. Crop
      plants are often grown on soils subject to waterlogging and many are sensitive to
      waterlogging of the root zone. The combination of unfavourable weather conditions
      and suboptimal soil and irrigation techniques can result in severe yield losses.
      The molecular basis of the adaptation to transient low oxygen conditions has not
      been completely characterized, but progress has been made towards identifying
      genes and gene products induced during low oxygen conditions. Promoter elements
      and transcription factors involved in the regulation of anaerobically induced
      genes have been characterized. In this paper an account is presented of the
      molecular strategies that have been used in an attempt to increase flooding
      tolerance of crop plants.

PMID- 10938800
TI  - QTL: their place in engineering tolerance of rice to salinity.
AB  - Secondary salinization and its relationship to irrigation are strong incentives
      to improve the tolerance of crops to salinity and to drought. Achieving this
      through the pyramiding of physiological traits (phenotypic selection without
      knowledge of genotype) is feasible. However, wide application of this approach is
      limited by the practicalities of assessing not only the parents, but also large
      numbers of individuals and families in segregating generations. Genotypic
      information is required in the form of markers for any quantitative trait loci
      involved (marker-assisted selection) or of direct knowledge of the genes. In the
      absence of adequate candidate genes for salt tolerance, a quantitative trait
      locus/marker-assisted selection approach has been used here. Putative markers for
      ion transport and selectivity, identified from analysis of amplified fragment
      length polymorphism, had been discovered within a custom-made mapping population
      of rice. Here it is reported that none of these markers showed any association
      with similar traits in a closely related population of recombinant inbred lines
      or in selections of a cultivar. Whilst markers will be of value in using elite
      lines from the mapping population in backcrossing, this has to be considered
      alongside the effort required to develop and map any given population. This
      result cautions against any expectation of a general applicability of markers for
      physiological traits. It is concluded that direct knowledge of the genes involved
      is needed. This cannot be achieved at present by positional cloning. The
      elucidation of candidate genes is required. Here the problem lies not in the
      analysis of gene expression but in devising protocols in which only those genes
      of interest are differentially affected by the experimental treatments.

PMID- 10938801
TI  - Low temperature-induced changes in the distribution of H2O2 and antioxidants
      between the bundle sheath and mesophyll cells of maize leaves.
AB  - The distribution of antioxidants between bundle sheath and mesophyll cells of
      maize leaves was analysed in plants grown at 20 degrees C, 18 degrees C and 15
      degrees C. The purity of the isolated bundle sheath and mesophyll fractions was
      determined using compartment-specific marker enzymes. In plants grown at 15
      degrees C, ascorbate peroxidase, CuZn-superoxide dismutase (CuZn-SOD) and
      monodehydroascorbate reductase activities were increased in the bundle sheath
      cells, and glutathione reductase, dehydroascorbate reductase and
      monodehydroascorbate reductase activities were enhanced in the mesophyll cells.
      SOD was absent from the mesophyll of plants grown at 20 degrees C but an Fe-SOD
      activity was found in the mesophyll of plants grown at 15 degrees C. Foliar Mn
      SOD activities were decreased at 15 degrees C compared to 20 degrees C. Catalase
      was undetectable in the mesophyll extracts of plants grown at 15 degrees C.
      Ascorbate and glutathione contents were considerably higher in the mesophyll than
      the bundle sheath fractions of plants grown at 20 degrees C. The ratios of
      reduced to oxidized forms of these antioxidants were significantly decreased in
      the bundle sheath, but increased in the mesophyll of leaves grown at 15 degrees
      C. Foliar H2O2 accumulated at 15 degrees C compared to 20 degrees C. Most of the
      foliar H2O2 was localized in the mesophyll tissues at all growth temperatures.
      The differential distribution of antioxidants between leaf bundle sheath and
      mesophyll tissues, observed at 20 degrees C, is even more pronounced when plants
      are grown at 15 degrees C and may contribute to the extreme sensitivity of maize
      to low temperatures.

PMID- 10938802
TI  - Disturbance in the allocation of carbohydrates to regenerative organs in
      transgenic Nicotiana tabacum L.
AB  - Transgenic tobacco (Nicotiana tabacum L, cv. SR-1) expressing mannitol 1
      phosphate dehydrogenase, MTLD, in chloroplasts and myo-inositol O
      methyltransferase, IMT1, in the cytosol after crossing of lines which expressed
      these foreign genes separately has been analysed. Plants expressing both enzymes
      accumulated mannitol and D-ononitol in amounts comparable to those following
      single gene transfer and showed phenotypically normal growth during the
      vegetative stage. Induction of flowering for transgenovar and wild-type occurred
      at the same time, but during flowering the phenotype of the transformed plants
      changed. Compared to wild-type, transgenic plants were characterized by curled,
      smaller upper leaves and elongated stems during flowering; incomplete development
      of flower buds with shorter sepals and pedicels resulted in increased abortion.
      Flowers completing development were normal. The vegetative biomass of the
      transformed plants was slightly higher than that of wild-type. Concentrations of
      soluble sugars and potassium were lower than in wild-type only in the apical
      parts of the transgenic plants. Both enzymes, under control of the CaMV 35S
      promoter, promoted accumulation of mannitol and D-ononitol in the youngest leaves
      close to the vegetative meristem and in flowers, suggesting that their presence
      could signal lower sink demand leading to a decrease in carbon import to flowers
      and developing seed capsules. The interpretation here is that increases of inert
      carbohydrates in developing sinks interfere with metabolism, such as respiration
      or glycolysis. This interference may be less significant in source tissues during
      vegetative growth than in sink tissues during seed development.

PMID- 10938803
TI  - Bundle sheath proteins are more sensitive to oxidative damage than those of the
      mesophyll in maize leaves exposed to paraquat or low temperatures.
AB  - In maize leaves growth at low temperatures causes decreases in maximum catalytic
      activities of photosynthetic enzymes and reduced amounts of proteins, rather than
      effects on regulation or co-ordination of the photosynthetic processes. To test
      the hypothesis that differential localization of antioxidants between the
      different types of photosynthetic cell in maize leaves is a major determinant of
      the extreme sensitivity of maize leaves to chilling damage, oxidative damage to
      proteins, induced by incubation of maize leaves with paraquat, has been measured
      and compared with the effects incurred by growth at low temperatures. While the
      increase in protein carbonyl groups caused by paraquat treatment was much greater
      than that caused by low temperature growth conditions, most carbonyl groups were
      detected on bundle sheath proteins in both stress conditions. With one or two
      exceptions proteins located in the mesophyll tissues were free of protein
      carbonyl groups in both situations. Paraquat treatment caused a complete loss of
      the psaA gene products, modified the photosystem II reaction centre polypeptide,
      D1, and increased the number of peptides arising from breakdown of ribulose 1,5
      bisphosphate carboxylase oxygenase (Rubisco). In contrast, growth at 15 degrees C
      increased the abundance (but not number) of Rubisco breakdown products and
      decreased that of the psaB gene product while the psaA gene product and PEP
      carboxylase were largely unaffected. Since bundle sheath proteins are more
      susceptible to oxidative damage than those located in the mesophyll cells,
      strategies for achieving a more balanced system of antioxidant defence may be
      effective in improving chilling tolerance in maize.

PMID- 10938804
TI  - Plant responses to sulphur deficiency and the genetic manipulation of sulphate
      transporters to improve S-utilization efficiency.
AB  - Decreased inputs of S have increased the incidence of S-deficiency in crops,
      resulting in decreased yields and quality. Remediation by fertilizer application
      is not always successful because this often results in an uneven supply of S. The
      ability to respond to S-deficiency stress varies between crops and this is a
      target for the genetic improvement of S-utilization efficiency. Improved capture
      of resources, the accumulation of greater reserves of S and improved mechanisms
      for the remobilization of these reserves are required. It is an inability to over
      accumulate S and subsequently, effectively remobilize S-reserves, which restricts
      optimum S-use efficiency. Genetic manipulation of the transporters and their
      expression will contribute to overcoming these limitations. Control of gene
      expression limits excess uptake and activity of the assimilatory pathway: the
      endogenous expression of sulphate transporters is regulated by S-supply, with
      negative regulation from reduced S-containing compounds and positive regulation
      by O-acetylserine, the C/N skeleton precursor of cysteine. Constitutive
      expression of the transporter will remove this control and may enable the
      accumulation of sulphate reserves. Sulphate in the vacuole and other pools of
      reduced sulphur, such as glutathione or protein may be remobilized under S
      limiting conditions. Low efficiencies of these remobilization processes,
      particularly the remobilization of vacuolar sulphate, suggest that the
      transporters involved in the remobilization are a target for modification.
      Transporters are involved in facilitating the multiple trans-membrane transport
      steps between uptake of sulphate from the soil solution, and delivery to the site
      of reduction in the chloroplast or plastid. A gene family has been identified and
      phylogenetic relationships based on primary sequence information indicate
      multiple sub-groups. Groups which are expressed in roots, in shoots and in both
      tissue types are postulated, however, the functional roles for these groups and
      the identification of transporters involved in recycling remain to be confirmed.

PMID- 10938805
TI  - Isolation and analysis of thermotolerant mutants of wheat.
AB  - Thermotolerant mutants of wheat cv. Guardian were isolated by selecting survivors
      from 5-d-old seedlings of M2 populations exposed to 47 degrees C for 90 min.
      Progeny testing, using triphenyl tetrazolium chloride reduction as a measure of
      tissue viability, following heat stress treatment for 120 min at each of three
      temperatures (32, 38 and 50 degrees C), confirmed the thermotolerant nature of
      seedlings of 13 mutants. Mutants were isolated at frequencies of 0.1% and 0.2%
      following the use of sodium azide and ethyl methanesulphonate, respectively. The
      relative thermotolerance of ten of the mutants and 'Guardian' was then tested by
      exposing plants to heat stresses of 38 degrees C for 6 h in every 24 h for five
      successive days at one of four growth stages between seedling and anthesis. Pmax
      (light-saturated net photosynthetic rate) and chlorophyll content were compared
      in stressed and unstressed plants. The Pmax of 'Guardian' was depressed by at
      least 23% by heat stress at each stage; this inhibition was least at ear
      emergence and greatest at anthesis, the latter being associated with reduced sink
      size as a result of lowered seed set. The stress-induced inhibition of Pmax in
      'Guardian' plants at anthesis had not recovered 3 d after removal of the stress.
      Mutant lines exhibited different developmental profiles of Pmax thermostability.
      Mutant tht (thermotolerant) 10, for example, exhibited partial thermostability at
      each growth stage tested while the Pmax of mutant tht 2 was completely unaffected
      by heat stress at second node and ear emergence, but was as inhibited as that of
      'Guardian' at anthesis; heat stress applied at anthesis in tht 2, but not tht 10,
      was associated with reduced seed set. Generally, the inhibitory effect of heat
      stress on Pmax in the mutants was reflected in declines in chlorophyll content.
      The ten mutants were grouped into nine categories, on the basis of
      thermotolerance characteristics.

PMID- 10938806
TI  - Differentiation in plant epidermal cells.
AB  - The plant epidermis is a multifunctional tissue playing important roles in water
      relations, defence and pollinator attraction. This range of function is performed
      by a number of different types of specialized cells, which differentiate from the
      early undifferentiated epidermis in adaptively significant patterns and
      frequencies. These various cells show different degrees of morphological
      specialization, but there is evidence to suggest that even the less specialized
      cell types may require certain signals to ensure their correct differentiation
      and patterning. Epidermal cells may potentially adopt certain fates through a
      cell lineage based mechanism or a cell interaction mechanism. Work on stomatal
      development has focused on the cell lineage mechanism and work on trichome
      differentiation has focused on the cell interaction model. Recent work on the
      Arabidopsis trichome suggests that interactions between neighbouring cells
      reinforce initial differences, possibly in levels of gene expression or cell
      cycle stage, to commit cells to different developmental programmes. In this
      review these mechanisms are explored in a number of specialized cell types and
      the further interactions between different developmental programmes are analysed.
      It is in these interactions between differentiating cells adopting different cell
      fates that the key to the patterning of a multifunctional tissue must lie.

PMID- 10938807
TI  - Changes in chalazal cell walls and in the peroxidase enzymes of the crease region
      during grain development in barley.
AB  - In an investigation of the role of peroxidase enzymes in the differentiation of
      the tissues of the crease region of barley, plants of winter barley cv. Halcyon
      were grown from anthesis onwards in controlled conditions at a constant
      temperature of 16 degrees C. Four ears were harvested at 2-d intervals from 6 d
      after anthesis (daa) until 50 daa. Grains from mid-ear were used for (i) fresh
      and dry weight determinations, (ii) extraction of crease tissue for the
      determination of peroxidase activity and for the separation of isozymes of
      peroxidase by isoelectric focusing (IEF) and (iii) detection of lignin and
      suberin in the tissues of the crease using autofluorescence and cytochemistry.
      Peroxidase activity was located histochemically in the crease tissue of cv.
      Chariot. Scanning electron microscopy studies were carried out on developing
      grains of cv. Blenheim. Maximum grain water content was achieved at 14 daa.
      Lignin and suberin were detected in the walls of the chalazal cells from 18 daa
      onwards. No changes in the staining of chalazal cell walls were detected at the
      end of grain filling (32 daa), but loss of autofluorescence and staining were
      observed at 42 daa, just prior to the final, rapid phase of grain dehydration.
      Peroxidase activity per fresh weight of crease tissue was high at 6 daa and low
      at 22 daa. It was also low between 32 and 40 daa, but it rose again from 42 daa
      onwards. IEF demonstrated that both anionic and cationic isozymes of peroxidase
      were present in crease tissue, the pattern of bands showing some marked changes
      during the course of grain development.

PMID- 10938808
TI  - Immunolocalization of actin in root statocytes of Lens culinaris L.
AB  - Lentil root statocytes show a strict structural polarity of their organelles with
      respect to the g vector. These cells are involved in the perception of gravity
      and are responsible for the orientation of the root. Actin filaments take part in
      the positioning of their organelles and could also be involved in the
      transduction of the gravitropic signal. A pre-embedding immunogold silver
      technique was carried out with a monoclonal antibody in order to study the
      distribution of actin cytoskeleton in the statocytes at the electron microscopic
      level. Some areas were never labelled (cell wall, vacuole, nucleoplasm,
      mitochondria, starch grains of the amyloplasts) or very slightly labelled (stroma
      of the amyloplasts). The labelling was scattered in the cytoplasm always close
      to, or on the nuclear and amyloplast envelopes and the tonoplast. Associations of
      2 to 6 dots in file were observed, but these short files were not oriented in one
      preferential direction. They corresponded to a maximum distance of 0.9 micron.
      This work demonstrated that each statocyte organelle was enmeshed in an actin web
      of short filaments arranged in different ways. The images obtained by
      rhodaminephalloidin staining were in accordance with those of immunogold
      labelling. The diffuse fluorescence of the cytoplasm could be explained by the
      fact that the meshes of the web should be narrow. The vicinity of actin and of
      the amyloplasts envelope could account for the movement of these organelles that
      was observed in spatial microgravity.

PMID- 10938809
TI  - Endo-beta-mannanase activity increases in the skin and outer pericarp of tomato
      fruits during ripening.
AB  - Activity of endo-beta-mannanase increases during ripening of tomato (Lycopersicon
      esculentum Mill.) fruit of the cultivar Trust. beta-Mannoside mannohydrolase is
      also present during ripening, but its pattern of activity is different from that
      of endo-beta-mannanase. The increase in endo-beta-mannanase activity is greatest
      in the skin, and less in the outer and inner pericarp regions. This enzyme is
      probably bound to the walls of the outermost cell layers of the fruit during
      ripening, and it requires a high-salt buffer for effective extraction. The enzyme
      protein, as detected immunologically on Western blots, is present during the
      early stages of ripening, before any enzyme activity is detectable. The mRNA for
      the enzyme is also present at these stages; endo-beta-mannanase may be produced
      and sequestered in a mature-sized inactive form during early ripening. Most non
      ripening mutants of tomato exhibit reduced softening and lower endo-beta
      mannanase activity, but a cause-and-effect relationship between the enzyme and
      ripening is unlikely because some cultivars which ripen normally do not exhibit
      any endo-beta-mannanase activity in the fruit.

PMID- 10938810
TI  - Nitrate assimilation in chicory roots (Cichorium intybus L.) which acquire radial
      growth.
AB  - Nitrate assimilation was analysed in chicory plants (Cichorium intybus L. cv.
      Turbo) during the early vegetative growth. Nitrate reductase (NR, EC 1.6.6.1)
      activity (NRA) was measured in roots and leaves at different developmental
      stages. During phase I, which corresponds to the structural growth (21-42 DAS),
      nitrate reduction mainly occurred in the roots. At the onset of the tuber
      formation (phase II), which is characterized by the formation of a cambium
      inducing a radial growth (42-63 DAS), NRA rapidly decreased in roots and
      developed in leaves. A tight correlation was found between the nitrate content,
      the amino acid level and NRA in roots and leaves. Northern blot and ELISA
      analysis showed that both levels of NR mRNA and NR protein were not modified
      during the time-course of the experiment suggesting that modification of nitrate
      assimilation was not controlled at a transcriptional level. In vitro NRA assayed
      in presence of either Mg2+ ions or EDTA showed that NR was influenced at least in
      part by a reversible phosphorylation/dephosphorylation reaction. Okadaic acid, a
      serine-threonine protein phosphatases inhibitor, strongly decreased NRA.
      Conversely, staurosporine, a serine-threonine protein kinases inhibitor, did not
      significantly change NRA in roots or leaves. Therefore, NRA was regulated at a
      post-translational level during the early vegetative growth by modifying the
      phosphorylation balance of the NR protein in chicory.

PMID- 10938811
TI  - Radial hydraulic conductivity along developing onion roots.
AB  - Although most studies have shown that water uptake varies along the length of a
      developing root, there is no consistent correlation of this pattern with root
      anatomy. In the present study, water movement into three zones of onion roots was
      measured by a series of mini-potometers. Uptake was least in the youngest zone
      (mean hydraulic conductivity, Lpr = 1.5 x 10(-7) +/- 0.34 x 10(-7) m MPa-1 s-1;
      +/- SE, n = 10 roots) in which the endodermis had developed only Casparian bands
      and the exodermis was immature. Uptake was significantly greater in the middle
      zone (Lpr = 2.4 x 10(-7) +/- 0.43 x 10(-7) m MPa-1 s-1; +/- SE, n = 10 roots)
      which had a mature exodermis with both Casparian bands and suberin lamellae, and
      continued at this level in the oldest zone in which the endodermis had also
      developed suberin lamellae (Lpr = 2.8 x 10(-7) +/- 0.30 x 10(-7) m MPa-1 s-1; +/-
      SE, n = 10 roots). Measurements of the hydraulic conductivities of individual
      cells (Lp) in the outer cortex using a cell pressure probe indicated that this
      parameter was uniform in all three zones tested (Lp = 1.3 x 10(-6) +/- 0.01 x 10(
      6) m MPa-1 s-1; +/- SE, n = 60 cells). Lp of the youngest zone was lowered by
      mercuric chloride treatment, indicating the involvement of mercury-sensitive
      water channels (aquaporins). Water flow in the older two root zones measured by
      mini-potometers was also inhibited by mercuric chloride, despite the demonstrated
      impermeability of their exodermal layers to this substance. Thus, water channels
      in the epidermis and/or exodermis of the older regions were especially
      significant for water flow. The results of this and previous studies are
      discussed in terms of two models. The first, which describes maize root with an
      immature exodermis, is the 'uniform resistance model' where hydraulic resistances
      are evenly distributed across the root cylinder. The second, which describes the
      onion root with a mature exodermis, is the 'non-uniform resistance model' where
      resistances can be variable and are concentrated in a certain layer(s) on the
      radial path.

PMID- 10938812
TI  - Weather and nodule mediated variations in delta 13C and delta 15N values in field
      grown soybean (Glycine max L.) with special interest in the analyses of xylem
      fluids.
AB  - The nodulating soybean (Enrei) and its non-nodulating mutant (EN 1282) were grown
      in outdoor plots for 2 years (1994: extraordinary dry, high temperature, 1995:
      ordinary year). Carbon and nitrogen accumulation, delta 13C and delta 15N values
      in plant parts and xylem fluids and delta 15N values in the water-extractable
      soil N were analysed throughout the growing period. Plant growth in 1994 was
      rapid during the early growth stages, but no pods were produced. In 1995, plant
      growth was normal and pods were formed. The delta 13C values of the leaves were
      less negative in 1994 than in 1995 and the nodulated plants showed less negative
      delta 13C values than non-nodulated plants in both years. The delta 13C values of
      the leaves during the vegetative phase were positively correlated to the leaf N
      concentrations. Leaf N concentrations in their turn were influenced by nodulation
      and weather conditions and/or soil available N. The delta 15N values in the
      plants and xylem fluids were lower in the nodulated soybean than in non-nodulated
      soybean in both years, and estimates of the contribution of N2 fixation in
      nodulated plants based on plant top delta 15N values were 7-14% in 1994 and 37
      63% in 1995. The delta 13C values of xylem fluids did not differ between
      nodulated and non-nodulated plants. Thus, the expected contribution by
      phosphopenolpyruvate carboxylase-mediated CO2 fixation in the root nodules to
      plant C-incorporation could not have been significant.

PMID- 10938813
TI  - Spatial and temporal distribution of solutes in the developing carrot taproot
      measured at single-cell resolution.
AB  - The time-course and spatial distribution of sugars and ions in carrot (Daucus
      carota L.) was studied at fine resolution using single cell (SiCSA) and tissue
      analysis. Four phases of osmolyte accumulation in the taproot were identified: an
      amino acid (germination) phase, when internal sources of amino acids provide
      seedlings with osmotica; an ion phase, when inorganic and organic ions were the
      main solutes; a hexose phase, when concentrations of glucose and fructose sharply
      increased and reached their maximum; and a sucrose phase, when sucrose became the
      major solute. Spatial distribution of sugar in taproot cells showed a general
      trend of highest concentration on both sides of the vascular cambium (some 200 mM
      sucrose, 150 mM glucose) and a minimum in the pith (some 100 mM sucrose, 60 mM
      glucose) and in periderm. Electrolytes (e.g. potassium) followed a distribution
      generally reciprocal to that of sugars; minimum in the tissue adjacent to the
      cambium (some 10 mM) and maximum in the pith and periderm (some 60-100 mM). The
      cambial cells contained unexpectedly low concentrations of sugars and potassium.
      These spatial and temporal patterns indicate that amino acids, other electrolytes
      and sugars are interchangeable in the tissue osmotic balance. The nature of the
      solute is developmentally determined both temporally and spatially. During the
      accumulation of electrolytes following the initial amino acid phase, osmotic
      pressure to 420 mosmol kg-1 rises and then remains constant despite large changes
      in the concentration of individual solutes. This indicates that osmotic pressure
      is regulated independently of the individual concentrations of solutes.

PMID- 10938814
TI  - Auxin-dependent cell wall depositions in the epidermal periplasmic space of
      graviresponding nodes of Tradescantia fluminensis.
AB  - Differential growth of the nodal regions of graviresponding Tradescantia
      fluminensis (Wandering Jew) was analysed with special respect to the extension
      restricting epidermal cells of the opposite growing and growth-inhibited organ
      flanks. Gravicurvature of horizontally gravistimulated isolated nodes depends on
      auxin (indolyl-3-acetic acid, IAA) and shows a node-specific profile in which the
      third node below the tip showed the greatest response. Exogenously supplied
      gibberellic acid induced no gravitropic growth. Vertically oriented isolated
      nodes supplied with exogenous IAA showed, on an electron microscopical level,
      conspicuous membrane invaginations with adjacent wall depositions restricted to
      the outer tangential epidermal cell walls. Their number was more than doubled by
      exogenously supplied Ca2+, which inhibited IAA-induced growth. No such changes
      could be detected in water-incubated segments or inner tissues of IAA-supplied
      segments. Gravistimulated differential growth of nodes of intact shoots and of
      nodal segments was characterized by changes similar to the ones induced by
      exogenous IAA, with greatly increased numbers of wall depositions within the
      epidermal cells of the growth-inhibited upper organ flank. Similar to the
      gravistimulated wall depositions, an asymmetric distribution pattern of Ca2+ was
      detected in the epidermal cell walls employing x-ray energy spectrum analysis
      (EDX). The results indicate that growth of nodes of Tradescantia fluminensis is
      regulated via IAA-induced secretion and subsequent infiltration of wall
      components enabling wall extension. The data support the hypothesis that
      temporary differential growth during gravicurvature of Tradescantia fluminensis
      is mediated by the antagonistic effect of Ca(2+)-ions on the infiltration of IAA
      induced wall-loosening components into the outer, extension-restricting epidermal
      walls thereby inhibiting growth.

PMID- 10938815
TI  - Low temperature sensing in tulip (Tulipa gesneriana L.) is mediated through an
      increased response to auxin.
AB  - Tulip (Tulipa gesneriana L.) is a bulbous plant species that requires a period of
      low temperature for proper growth and flowering. The mechanism of sensing the low
      temperature period is unknown. The study presented in this paper shows that the
      essential developmental change in tulip bulbs during cold treatment is an
      increase in sensitivity to the phytohormone auxin. This is demonstrated using a
      model system consisting of isolated internodes grown on tissue culture medium
      containing different combinations of the phytohormones auxin and gibberellin.
      Using mathematical modelling, equations taken from the field of enzyme kinetics
      were fitted through the data. By doing so it became apparent that longer periods
      of low temperature resulted in an increased maximum response at a lower auxin
      concentration. Besides the cold treatment, gibberellin also enhances the response
      to auxin in the internodes in this in vitro system. A working model describing
      the relationship between the cold requirement, gibberellin action and auxin
      sensitivity is put forward. Possible analogies with other cold-requiring
      processes such as vernalization and stratification, and the interaction of auxin
      and gibberellin in the stalk elongation process in other plant species are
      discussed.

PMID- 10938816
TI  - Cell wall adaptations to multiple environmental stresses in maize roots.
AB  - A municipal solid-waste bottom slag was used to grow maize plants under various
      abiotic stresses (high pH, high salt and high heavy metal content) and to analyse
      the structural and chemical adaptations of the cell walls of various root
      tissues. When compared with roots of control plants, more intensive wall
      thickenings were detected in the inner tangential wall of the endodermis. In
      addition, phi thickenings in the rhizodermis in the oldest part of the seminal
      root were induced when plants were grown in the slag. The role of the phi
      thickenings may not be a barrier for solutes as an apoplastic dye could freely
      diffuse through them. The chemical composition of cell walls from endodermis and
      hypodermis was analysed. Slag-grown plants had higher amounts of lignin in
      endodermal cell walls when compared to control plants and a higher proportion of
      H-type lignin in the cell walls of the hypodermis. Finally, the amount of
      aliphatic suberin in both endo- and hypodermal cell walls was not affected by
      growing the plants on slag. The role of these changes in relation to the increase
      in mechanical strengthening of the root is discussed.

PMID- 10938817
TI  - Effects on the growth of carrots (Daucus carota L.), cabbage (Brassica oleracea
      var. capitata L.) and onion (Allium cepa L.) of restricting the ability of the
      plants to intercept resources.
AB  - The objective of this paper is to assess the size and penetration of edge effects
      in carrot, cabbage and onion field crops and the extent to which these edge
      effects are modified by the presence of aerial or soil competition between the
      crop rows. In all three crops, large weight differences developed between the
      plants in the edge rows and those in the central rows. There was no indication of
      plant weight fluctuating between large and small values with each successive row
      in from the edge, as suggested by others. In carrot and onion, edge effects were
      greatly reduced by the presence of either white reflective aerial partitions or
      soil partitions, indicating that these species competed for both light and soil
      resources in UK field conditions. In cabbage, the mere presence of clear aerial
      partitions between rows reduced edge effects and there was little effect of soil
      partitions. This indicates the predominance of shoot over root competition in
      this species. The differences between species are possibly related to the
      architectural flexibility of their shoots. These results suggest that, within
      crops, carrot and onion plants compete for light over a distance of about 20 cm
      in each direction and for below-ground resources over a distance of about 50 cm
      in each direction. For cabbage, interactions between plants appeared to be
      dominated by the requirement for sufficient space to deploy the shoots for
      efficient light interception.

PMID- 10938818
TI  - Brittleness of twig bases in the genus Salix: fracture mechanics and ecological
      relevance.
AB  - The twig bases within the genus Salix were investigated. Brittleness of twig
      bases as defined in the literature neither correlates with Young's modulus nor
      with growth strains, which were measured for S. alba, S. fragilis and S. x
      rubens. For the species S. alba, S. appendiculata, S. eleagnos, S. fragilis, S.
      purpurea, S. triandra, S. viminalis, and S. x rubens, fracture surfaces of broken
      twigs were investigated and semiquantitatively described in terms of 'relative
      roughness' (ratio of rough area of fracture surface over whole area of fracture
      surface). The relative roughness clearly corresponds with the classification into
      brittle and nonbrittle species given in the literature. An attempt was made to
      quantify brittleness with mechanical tests. The absolute values of stress and
      strain do not correlate with the brittleness of the twig bases as defined by the
      relative roughness. However, the 'index stress' (ratio of stress at yield over
      stress at fracture) or the 'index strain' (ratio of strain at yield over strain
      at fracture), correlate well with the relative roughness. The graphic analysis of
      index stress against index strain reveals a straight line on which the eight
      species are ordered according to their brittleness. Depending on growth form and
      habitat, brittle twig bases of willows may function ecologically as mechanical
      safety mechanisms and, additionally, as a propagation mechanism.

PMID- 10938819
TI  - A study of water relations in neem (Azadirachta indica) seed that is
      characterized by complex storage behaviour.
AB  - Neem (Azadirachta indica) seed is reputed to have limited tolerance to
      desiccation, to be sensitive to chilling and imbibitional stress, and to display
      intermediate storage behaviour. To understand this behaviour the properties of
      water in seed tissues were studied. Water sorption isotherms showed that at
      similar relative humidity (RH), the water content was consistently higher in axes
      than in cotyledons, mainly due to the elevated lipid content (51%) in the
      cotyledons. Using differential scanning calorimetry, melting transitions of water
      were observed at water contents higher than 0.14 g H2O g-1 DW in the cotyledons
      and 0.23 g H2O g-1 DW in the axes. Beside melting transitions of lipid, as
      verified by infrared spectroscopy, changes in heat capacity were observed which
      shifted with water content, indicative of glass-to-liquid transitions. State
      diagrams are given on the basis of the water content of seed tissues, and also on
      the basis of the RH at 20 degrees C. Longevity was considerably improved, and the
      sensitivity to chilling/subzero temperatures was reduced when axis and cotyledons
      were dehydrated to moisture contents < or = of approximately 0.05 g H2O g-1 DW.
      However, longevity during storage at very low water contents was limited. A
      possible mechanism for the loss of sensitivity to chilling/subzero temperatures
      at low water contents is discussed. The results suggest that dry neem seeds in
      the glassy state have great potential for extended storability, also at subzero
      temperatures.

PMID- 10938820
TI  - The effects of ethylene, depressed oxygen and elevated carbon dioxide on
      antioxidant profiles of senescing spinach leaves.
AB  - It has been suggested that antioxidants play a role in regulating or modulating
      senescence dynamics of plant tissues. Ethylene has been shown to promote early
      plant senescence while controlled atmospheres (CA; reduced O2 levels and elevated
      CO2 levels) can delay its onset and/or severity. In order to examine the possible
      importance of various antioxidants in the regulation of senescence, detached
      spinach (Spinacia oleracea L.) leaves were stored for 35 d at 10 degrees C in one
      of three different atmospheres: (1) ambient air (0.3% CO2, 21.5% O2, 78.5% N2),
      (2) ambient air + 10 ppm ethylene to promote senescence, or (3) CA (10% CO2, 0.8%
      O2 and 89.2% N2) to delay senescence. At weekly intervals, material was assessed
      for activities of the antioxidant enzymes ascorbate peroxidase (ASPX; EC
      1.11.1.11), catalase (CAT; EC 1.11.1.6), dehydroascorbate reductase (DHAR; EC
      1.8.5.4), glutathione reductase (GR; EC 1.6.4.2), monodehydroascorbate reductase
      (MDHAR; EC 1.6.5.4), and superoxide dismutase (SOD; EC 1.15.1.1), and
      concentrations of the water-soluble antioxidant compounds ascorbate and
      glutathione. Indicators of the rate and severity of senescence (lipid
      peroxidation, chlorophyll, and soluble protein levels) were also determined.
      Results indicated that the rate and severity of senescence was similar between
      the leaves stored in ambient air or CA until day 35, at which point the ambient
      air-stored leaves exhibited a sharp increase in lipid peroxidation. Tissues under
      both storage regimes demonstrated significant declines only in levels of ASPX,
      CAT, and ascorbate. Glutathione content in the CA-stored tissue also
      significantly dropped, but only on day 35. In contrast, spinach leaves stored in
      ambient air + ethylene experienced a rapid decrease in levels of all the
      antioxidants assessed except SOD. Declines in levels of ASPX, CAT, and ascorbate
      over the 35 d storage period regardless of the composition of the storage
      atmosphere suggests that regulation of H2O2 levels plays an important role in
      both the dynamics and severity of post-harvest senescence of spinach.

PMID- 10938821
TI  - pH, abscisic acid and the integration of metabolism in plants under stressed and
      non-stressed conditions: cellular responses to stress and their implication for
      plant water relations.
AB  - A paradigm for the response of plants to stress is presented which suggests that
      plants move towards a state of minimal metabolic activity as a stress intensifies
      and remain in that state until that stress is relieved. The paradigm is based on
      the proposition that cells that interface with the transpiration stream employ
      variations on the following theme to move towards that state. Tension on the
      apoplastic water opens a mechanosensitive Ca2+ channel, a response that is
      augmented by apoplastic ABA. The resulting elevated cytoplasmic Ca2+ deactivates
      a plasmalemma H+/ATPase and also activates a K(+)-H+ symport. The inflow of K+
      and H+ depolarizes the membrane and renders the apoplast less acidic, the protons
      being removed to the vacuole and the K+ ions being re-exported via the K+ outward
      rectifying channel. The onset of darkness in guard and mesophyll cells
      deactivates the plasmalemma H+/ATPase and then the events outlined above ensue
      except that these cells do not appear to utilize either Ca2+ or ABA during these
      changes. In stressed cells it is proposed that elevated cytoplasmic Ca2+
      activates the release of an ABA precursor from a stored form. ABA is then
      released in the apoplast after export of the precursor if the activity of the
      K(+)-H+ symport has brought the apoplastic pH close to 7.0. It is proposed that
      aquaporins in the xylem parenchyma and mesophyll cells are opened by elevated
      cytoplasmic Ca2+ when the water potential of the transpiration stream is high so
      that water can be stored in the 'xylem parenchyma reservoir'. The water in this
      reservoir is then used to increase the water potential in the transpiration
      stream when the water column is under tension and to help repair embolisms by a
      mechanism that resembles stomatal closure.

PMID- 10938822
TI  - Photosynthetic carbohydrate metabolism in the resurrection plant Craterostigma
      plantagineum.
AB  - The resurrection plant Craterostigma plantagineum (Hochst) is able to survive
      almost complete tissue dehydration when water is withheld from it, and then can
      rehydrate rapidly on rewatering. This ability is believed to be the result of the
      accumulation of sucrose in aerial tissues as a result of metabolism of 2
      octulose. In this work the metabolic activity of well-watered Craterostigma
      plantagineum plants has been investigated. It is shown that Craterostigma makes
      raffinose series oligosaccharides as a product of photosynthesis and translocates
      them in the phloem. Evidence is also provided that 2-octulose is a product of
      photosynthesis and accumulates in the leaves over the light period and is
      mobilized at night. Thus 2-octulose acts as a temporary storage carbohydrate in
      leaves during photosynthesis in a similar fashion to starch in most C3 plants.
      Other potential roles of 2-octulose are discussed. Other than these observations
      Craterostigma plants are very similar to other C3 plants under these conditions.

PMID- 10938823
TI  - Maternal genotype influences pea seed size by controlling both mitotic activity
      during early embryogenesis and final endoreduplication level/cotyledon cell size
      in mature seed.
AB  - When reciprocal crosses are made between different pea genotypes, there is a
      strong maternal influence on mature seed size of the reciprocal hybrids, i.e.
      their dry weights are similar to that of seeds obtained from their maternal
      parents. Reciprocal crosses between pea varieties having very different mature
      seed sizes were used to investigate how the maternal genotype controls seed
      development and mature seed size. The differences in dry seed weight between
      genotypes and reciprocal hybrids reflected differences in both cotyledon cell
      number and mean cell volume, and the maternal control on the establishment of
      these two traits was investigated. Using flow cytometry, data relative to
      endoreduplication kinetics in cotyledons during the transition between the cell
      division phase and maturation were obtained. The appearance of nuclei having an
      8C DNA content indicates the initiation of the endoreduplication phenomenon and
      thus the end of the cell division phase. It was shown that the duration of the
      cell division phase was the same in the reciprocal hybrids, its value being
      intermediate between those recorded for their maternal parents. This result
      indicates that the timing of development of the embryo is not under maternal
      control, but depends on its own genotype. Consequently, maternal genotype must
      influence the mitotic rate during the cell division phase to achieve differences
      in cell number found in the cotyledons of mature F1-reciprocal hybrids. The final
      level of endoreduplication in cotyledons of mature seeds was also investigated.
      This study showed that there is a close relationship (r2 = 0.919) between the
      endoreduplication level in mature cotyledons and seed dry weight or mean volume
      of cotyledon cells, suggesting that both maternal and non-maternal factors could
      control the number of endoreduplicating cycles in the cotyledons and,
      hypothetically, the cotyledon cell size.

PMID- 10938824
TI  - Improved tolerance to salinity and low temperature in transgenic tobacco
      producing glycine betaine.
AB  - Glycine betaine is an osmoprotectant found in many organisms, including bacteria
      and higher plants. The bacterium Escherichia coli produces glycine betaine by a
      two-step pathway where choline dehydrogenase (CDH), encoded by betA, oxidizes
      choline to betaine aldehyde which is further oxidized to glycine betaine by the
      same enzyme. The second step, conversion of betaine aldehyde into glycine
      betaine, can also be performed by the second enzyme in the pathway, betaine
      aldehyde dehydrogenase (BADH), encoded by betB. Transformation of tobacco
      (Nicotiana tabacum), a species not accumulating glycine betaine, with the E. coli
      genes for glycine betaine biosynthesis, resulted in transgenic plants
      accumulating glycine betaine. Plants producing CDH were found to accumulate
      glycine betaine as did F1 progeny from crosses between CDH- and BADH-producing
      lines. Plants producing both CDH and BADH generally accumulated higher amounts of
      glycine betaine than plants producing CDH alone, as determined by 1H NMR
      analysis. Transgenic tobacco lines accumulating glycine betaine exhibited
      increased tolerance to salt stress as measured by biomass production of
      greenhouse-grown intact plants. Furthermore, experiments conducted with leaf
      discs from glycine betaine-accumulating plants indicated enhanced recovery from
      photoinhibition caused by high light and salt stress as well as improved
      tolerance to photoinhibition under low temperature conditions. In conclusion,
      introduction of glycine betaine production into tobacco is associated with
      increased stress tolerance probably partly due to improved protection of the
      photosynthetic apparatus.

PMID- 10938825
TI  - Cytodifferentiation and transformation of embryogenic callus lines derived from
      anther culture of wheat.
AB  - Three types of callus tissues established from anther culture of eleven doubled
      haploid (DH) lines of wheat (Triticum aestivum L.) were evaluated for their
      ability in enhancing friable embryogenic (Type II) culture differentiation and
      genetic transformation. Differences between types of callus inocula were highly
      significant (P < 0.001), suggesting that the quality of the initial callus
      explant is of profound importance in encouraging the proliferation of Type II
      cultures. Other factors found to be crucial included weekly subculture of friable
      embryogenic callus tissues on a maintenance medium containing 30 microM dicamba
      and a predominance of amino-acid nitrogen supplement. Transfer and integration of
      the beta-glucuronidase gene was also affected by the type of inoculum when
      suitable embryogenic cell cultures were transformed using silicon carbide
      whiskers and high velocity microprojectiles. Expression of the hygromycin
      phosphotransferase selectable marker gene sequence was confirmed in all the
      stably transformed cell lines maintained on selection media containing lethal
      levels of hygromycin. Comparatively, there were differences in the frequency of
      regenerable, transgenic clonal segments between whisker-treated and
      microprojectile bombarded tissues mainly as a result of the fact that cultures
      vortexed with whiskers were more capable of post-treatment cell proliferation and
      embryo differentiation than those bombarded with cDNA-coated microprojectiles.
      Conditions for obtaining these results are outlined and discussed in relation to
      the suitability of the two transformation strategies for producing transgenic
      cell aggregates of wheat.

PMID- 10938826
TI  - ABA activation of an MBP kinase in Pisum sativum epidermal peels correlates with
      stomatal responses to ABA.
AB  - In-gel protein kinase assays using myelin basic protein (MBP) as substrate have
      been used to demonstrate that abscisic acid (ABA) activates an MBP kinase (AMBP
      kinase) in epidermal peels prepared from leaves of the Argenteum mutant of pea,
      Pisum sativum L. AMBP kinase has the characteristics of a mitogen-activated
      protein kinase (MAPK): it utilizes MBP preferentially as an artificial substrate,
      it is rapidly and transiently activated, it is of the appropriate size (molecular
      weight c. 45 kDa), requires tyrosine phosphorylation for activity and is tyrosine
      phosphorylated upon activation. Reverse transcription-PCR was used to generate a
      previously-cloned MAPK from guard cells, epidermis and mesophyll and
      immunoblotting using an antibody raised against a mammalian MAPK detected MAPK
      related proteins, including one of 45 kDa, in epidermal peels, mesophyll and
      guard cells. Inhibition of AMBP kinase activation by PD98059, a specific
      inhibitor of MAPK kinase, and thus MAPK activation, correlated with PD98059
      inhibition of ABA-induced stomatal closure and dehydrin gene expression,
      suggesting that ABA effects in pea epidermal peels require MAPK activation. AMBP
      kinase was not activated by ABA in guard cells isolated by enzyme treatment.
      However, a protein kinase of c. 43 kDa was activated by ABA in isolated guard
      cells, but not in mesophyll or epidermal tissue.

PMID- 10938827
TI  - Intracellular pH regulation in maize root tips exposed to ammonium at high
      external pH.
AB  - Ammonium-induced changes in the cytoplasmic and vacuolar pH values of excised
      maize (Zea mays L.) root tips, measured by in vivo 31P nuclear magnetic resonance
      (NMR) spectroscopy, were correlated with the ammonium content of the tissue,
      determined by 14N NMR. Calculations based on these measurements indicated that
      the pH changes observed during exposure to 10 mM ammonium for 1 h at pH 9.0, and
      in the recovery following the removal of the external ammonium supply, were
      largely determined by the influx and efflux of the weak base NH3. Carboxylate
      synthesis, detected by both in vivo 13C NMR and the incorporation of
      [14C]bicarbonate, was stimulated by the ammonium-induced alkalinization of the
      root tips, but the contribution that this proton-generating process made to pH
      regulation during and after the ammonium treatment was quantitatively
      insignificant. Similarly, ammonium assimilation, which was shown to occur via the
      proton-generating glutamine synthetase/glutamate synthase pathway using in vivo
      15N NMR, was also quantitatively insignificant in comparison with the large
      changes in ammonium content that occurred during the ammonium treatment and
      subsequent recovery. The results are discussed in relation to several recent
      studies in which ammonium was used to perturb intracellular pH values, and it is
      argued (i) that a new method for probing the subcellular compartmentation of
      amino acids, based on an ammonium-induced alkalinization of the cytoplasm may be
      difficult to implement in dense heterogeneous tissues; and (ii) that observations
      on the apparently proton-consuming effect of ammonium assimilation in rice root
      hairs may actually reflect unusually rapid assimilation.

PMID- 10938828
TI  - Uptake and retranslocation of leaf-applied cadmium (109Cd) in diploid, tetraploid
      and hexaploid wheats.
AB  - Uptake and retranslocation of leaf-applied radiolabeled cadmium (109Cd) was
      studied in three diploid (Triticum monococcum, AA), four tetraploid (Triticum
      turgidum, BBAA) and two hexaploid (Triticum aestivum, BBAADD) wheat genotypes
      grown for 9 d under controlled environmental conditions in nutrient solution.
      Among the tetraploid wheats, two genotypes were primitive (ssp. dicoccum) and two
      genotypes modern wheats (ssp. durum). Radiolabelled Cd was applied by immersing
      the tips (3 cm) of mature leaf into a 109Cd radiolabelled solution. There was a
      substantial variation in the uptake and export of 109Cd among and within wheat
      species. On average, diploid wheats (AA) absorbed and translocated more 109Cd
      than other wheats. The largest variation in 109Cd uptake was found within
      tetraploid wheats (BBAA). Primitive tetraploid wheats (ssp. dicoccum) had a
      greater uptake capacity for 109Cd than modern tetraploid wheats (ssp. durum). In
      all wheats studied, the amount of the 109Cd exported from the treated leaf into
      the roots and the remainder of the shoots was poorly related to the total
      absorption. For example, bread wheat cultivars were more or less similar in total
      absorption, but differed greatly in the amount of 109Cd retranslocated. The
      diploid wheat genotype 'FAL-43' absorbed the lowest amount of 109Cd, but
      retranslocated the greatest amount of 109Cd in roots and remainder of shoots. The
      results indicate the existence of substantial genotypic variation in the uptake
      and retranslocation of leaf-applied 109Cd. This variation is discussed in terms
      of potential genotypic differences in binding of Cd to cell walls and the
      composition of phloem sap ligands possibly affecting Cd transport into sink
      organs.

PMID- 10938829
TI  - Rapid effects of nitrogen form on leaf morphogenesis in tobacco.
AB  - Ammonium (NH4+) instead of nitrate (NO3-) as the nitrogen (N) source for tobacco
      (Nicotiana tabacum L.) cultivated in a pH-buffered nutrient solution resulted in
      decreased shoot and root biomass. Reduction of shoot fresh weight was mainly
      related to inhibition of leaf growth, which was already detectable after short
      term NH4+ treatments of 24 h, and even at a moderate concentration level of 2 mM.
      Microscopic analysis of the epidermis of fully expanded leaves revealed a
      decrease in cell number (50%) and in cell size (30%) indicating that both cell
      division and cell elongation were affected by NH4+ application. Changes in
      various physiological parameters known to be associated with NH4(+)-induced
      growth depression were examined both in long-term and short-term experiments: the
      concentrations of total N, soluble sugars and starch as well as the osmotic
      potential, the apparent hydraulic conductivity and the rate of water uptake were
      not reduced by NH4+ treatments (duration 1-12 d), suggesting that leaf growth was
      neither limited by the availability of N and carbohydrates, nor by a lack of
      osmotica or water supply. Although the concentration of K+ in leaf press sap
      declined in expanding leaves by approximately 15% in response to NH4+ nutrition,
      limitation of mineral nutrients seems to be unlikely in view of the fast response
      of leaf growth at 24 h after the start of the NH4+ treatment. No inhibitory
      effects were observed when NH4+ and NO3- were applied simultaneously (each 1 mM)
      resulting in a NO3-/NH4+ net uptake ratio of 6:4. These findings suggest that the
      rapid inhibition of leaf growth was not primarily related to NH4+ toxicity, but
      to the lack of NO3(-)-supply. Growth inhibition of plants fed solely with NH4+
      was associated with a 60% reduction of the zeatine + zeatine riboside (Z + ZR)
      cytokinin fraction in the xylem sap after 24 h. Furthermore Z + ZR levels
      declined to almost zero within the next 4 d after start of the NH4+ treatment. In
      contrast, the concentrations of the putative Z + ZR precursors isopentenyl
      adenine and isopentenyl-adenosine (i-Ade + i-Ado) were not affected by NH4+
      application. Since cytokinins are involved in the regulation of both cell
      division and cell elongation, it seems likely that the presence of NO3- is
      required to maintain biosynthesis and/or root to shoot transfer of cytokinins at
      a level that is sufficient to mediate normal leaf morphogenesis.

PMID- 10938830
TI  - The influence of supra-optimal root-zone temperatures on growth and stomatal
      conductance in Capsicum annuum L.
AB  - Pepper (Capsicum annuum L.) plants were grown aeroponically in a Singapore
      greenhouse under natural diurnally fluctuating ambient shoot temperatures, but at
      two different root-zone temperatures (RZTs): a constant 20 +/- 2 degrees C RZT
      and a diurnally fluctuating ambient (A) (25-40 degrees C) RZT. Plants grown at 20
      RZT had more leaves, greater leaf area and dry weight than A-RZT plants.
      Reciprocal transfer experiments were conducted between RZTs to investigate the
      effect on plant growth, stomatal conductance (gs) and water relations. Transfer
      of plants from A-RZT to 20-RZT increased plant dry weight, leaf area, number of
      leaves, shoot water potential (psi shoot), and gs; while transfer of plants from
      20-RZT to A-RZT decreased these parameters. Root hydraulic conductivity was
      measured in the latter transfer and decreased by 80% after 23 d at A-RZT.
      Transfer of plants from 20-RZT to A-RZT had no effect on xylem ABA concentration
      or xylem nitrate concentration, but reduced xylem sap pH by 0.2 units. At both
      RZTs, gs measured in the youngest fully expanded leaves increased with plant
      development. In plants with the same number of leaves, A-RZT plants had a higher
      gs than 20-RZT plants, but only under high atmospheric vapour pressure deficit.
      The roles of chemical signals and hydraulic factors in controlling gs of
      aeroponically grown Capsicum plants at different RZTs are discussed.

PMID- 10938831
TI  - Developmental pathway of somatic embryogenesis in Picea abies as revealed by time
      lapse tracking.
AB  - Several coniferous species can be propagated via somatic embryogenesis. This is a
      useful method for clonal propagation, but it can also be used for studying how
      embryo development is regulated in conifers. However, in conifers it is not known
      to what extent somatic and zygotic embryos develop similarly, because there has
      been little research on the origin and development of somatic embryos. A time
      lapse tracking technique has been set up, and the development of more than 2000
      single cells and few-celled aggregates isolated from embryogenic suspension
      cultures of Norway spruce (Picea abies L. Karst.) and embedded in thin layers of
      agarose has been traced. Experiments have shown that somatic embryos develop from
      proembryogenic masses which pass through a series of three characteristic stages
      distinguished by cellular organization and cell number (stages I, II and III) to
      transdifferentiate to somatic embryos. Microscopic inspection of different types
      of structures has revealed that proembryogenic masses are characterized by high
      interclonal variation of shape and cellular constitution. In contrast, somatic
      embryos are morphologically conservative structures, possessing a distinct
      protoderm-like cell layer as well as embryonal tube cells and suspensor. The lack
      of staining of the arabinogalactan protein epitope recognized by the monoclonal
      antibody JIM13 was shown to be an efficient marker for distinguishing
      proembryogenic masses from somatic embryos. The vast majority of cells in
      proembryogenic masses expressed this epitope and none of cells in the early
      somatic embryos. The conditions that promote cell proliferation (i.e. the
      presence of exogenous auxin and cytokinin), inhibit somatic embryo formation;
      instead, continuous multiplication of stage I proembryogenic masses by unequal
      division of embryogenic cells with dense cytoplasm is the prevailing process.
      Once somatic embryos have formed, their further development to mature forms
      requires abscisic acid and shares a common histodifferentiation pattern with
      zygotic embryos. Although the earliest stages of somatic embryo development
      comparable to proembryogeny could not be characterized, the subsequent
      developmental processes correspond closely to what occurs in the course of early
      and late zygotic embryogeny. A model for somatic embryogenesis pathways in Picea
      abies is presented.

PMID- 10938832
TI  - Influence of high light and UV-B radiation on photosynthesis and D1 turnover in
      atrazine-tolerant and -sensitive cultivars of Brassica napus.
AB  - An atrazine-tolerant mutant and an atrazine-sensitive cultivar of Brassica napus
      L. were grown under visible radiation (400 mumol m-2 s-1, photosynthetically
      active radiation, PAR) and then subjected to treatment conditions. These included
      short-term high PAR (1600 mumol m-2 s-1) which was given for 4 h either alone or
      in combination with an enhanced level of UV-BBE radiation (4.6 kJ m-2 h-1
      biologically effective UV-B, 280-320 nm). Recovery from the radiation treatment
      was studied for 4 h under the light conditions for growth. Since it is known that
      the atrazine-tolerant mutant is susceptible to photoinhibition, one of the aims
      of the present study was to determine the effects of a supplemental, enhanced
      level of UV-B radiation with regard to the mutant. The results indicate an
      additive effect of UV-B radiation on Fv/Fm, photochemical yield and
      photosynthetic oxygen evolution during both exposure and recovery, and also a
      higher susceptibility of the mutant to photoinhibitory PAR conditions alone and
      in combination with UV-B, which may have implications in a changing environment.
      Both cultivars also showed a higher D1 turnover during the radiation stress than
      during recovery, as shown by immunoblotting and 35S-methionine incorporation
      measurements.

PMID- 10938833
TI  - Estimation of base temperatures for nine weed species.
AB  - Experiments were conducted to test several methods for estimating low temperature
      thresholds for seed germination. Temperature responses of nine weeds common in
      annual agroecosystems were assessed in temperature gradient experiments. Species
      included summer annuals (Amaranthus albus, A. palmeri, Digitaria sanguinalis,
      Echinochloa crus-galli, Portulaca oleracea, and Setaria glauca), winter annuals
      (Hirschfeldia incana and Sonchus oleraceus), and Conyza canadensis, which is
      classified as a summer or winter annual. The temperature below which development
      ceases (Tbase) was estimated as the x-intercept of four conventional germination
      rate indices regressed on temperature, by repeated probit analysis, and by a
      mathematical approach. An overall Tbase estimate for each species was the average
      across indices weighted by the reciprocal of the variance associated with the
      estimate. Germination rates increased linearly with temperature between 15
      degrees C and 30 degrees C for all species. Consistent estimates of Tbase were
      obtained for most species using several indices. The most statistically robust
      and biologically relevant method was the reciprocal time to median germination,
      which can also be used to estimate other biologically meaningful parameters. The
      mean Tbase for summer annuals (13.8 degrees C) was higher than that for winter
      annuals (8.3 degrees C). The two germination response characteristics, Tbase and
      slope (rate), influence a species' germination behaviour in the field since the
      germination inhibiting effects of a high Tbase may be offset by the germination
      promoting effects of a rapid germination response to temperature. Estimates of
      Tbase may be incorporated into predictive thermal time models to assist weed
      control practitioners in making management decisions.

PMID- 10938834
TI  - Effects of symbiosis with Frankia and arbuscular mycorrhizal fungus on the
      natural abundance of 15N in four species of Casuarina.
AB  - The effect of interactions between Casuarina species, Frankia strains and AMF on
      nitrogen isotope fractionation within the plant were determined under conditions
      where changes in source nitrogen were minimized by growing plants in mineral
      nitrogen-deficient conditions and without added organic N. Casuarina
      cunninghamiana, C. equisetifolia, C. glauca, and C. junghuniana were inoculated
      singly with three Frankia strains or were dual inoculated with Frankia and Glomus
      fasciculatum. The %N and delta 15N of separated parts of plants inoculated with
      the three Frankia strains or with Frankia + Glomus were not significantly
      different within Casuarina species. However, the slow-growing C. junghuniana
      differed in several variables from the other three species. There was a highly
      significant, linear relationship between the natural logarithms of cladode N
      content and delta 15N of plants of the four Casuarina species when inoculated
      with Frankia or with Frankia + Glomus, showing that nitrogen supply and the
      correlated variable, plant growth rate, were major determinants of delta 15N.
      Provision of small quantities of (NH4)2SO4 or KNO3 increased several-fold the
      growth of three of the Casuarina species when inoculated with Frankia alone or
      with Frankia + Glomus. Within species, mycorrhizal and non-mycorrhizal plants
      receiving supplementary soluble phosphate were of similar dry weights at harvest.
      delta 15N values for cladodes of C. cunninghamiana, C. equisetifolia and C.
      glauca were similar, but values for the poor growing C. junghuniana were more
      variable and, with the exception of plants receiving KNO3, were lower than those
      of the other three species. Reduced growth due to suboptimal availability of N or
      P had a major influence on delta 15N and, in these conditions where plants could
      not access significant amounts of organic N, outweighed any effects on cladode
      delta 15N of colonization by Glomus. delta 15N values of nodules were higher than
      other parts of Frankia or Frankia + Glomus inoculated Casuarinas, conceivably due
      to retention in nodules of fixed N, with delta 15N close to zero.

PMID- 10938836
TI  - The monoclonal antibody MAC252 does not react with the (-) enantiomer of abscisic
      acid.
AB  - An RIA procedure has been developed for ABA quantification using MAC62, a
      monoclonal antibody raised against (+)-cis, trans -ABA. This widely used method
      now relies on MAC252, a recloned version of the exhausted MAC62. Recently, it has
      been suggested that MAC252 was not able to discriminate between the (+) and (-)
      enantiomers of ABA. As this can be misleading when interpreting RIA results, it
      has been carefully examined here whether MAC252 reacts with (-)-ABA. MAC252
      exhibited negligible cross-reactivity with (-)-ABA, which was confirmed with
      commercial mixtures of ABA isomers. It is concluded that the RIA protocol can
      continue to be used with MAC252 as it was with MAC62.

PMID- 10938835
TI  - Dehydrin transcript fluctuations during a day/night cycle in drought-stressed
      sunflower.
AB  - To investigate environmental stimuli involved in the modulation of drought
      induced gene expression, the influence of the day/night cycle on the expression
      of two dehydrin genes (HaDhn1 and HaDhn2) in leaves of sunflowers subjected to
      mild or severe drought stress has been studied. It was observed that the HaDhn1,
      but not HaDhn2, transcript oscillated in a diurnal fashion. In severely stressed
      plants, the peak of HaDhn1 mRNA accumulation occurred at midday.

PMID- 10938837
TI  - The transmission of gas pressure to xylem fluid pressure when plants are inside a
      pressure bomb.
AB  - In earlier work tobacco leaves were placed in a Scholander-Hammel pressure bomb
      and the end of the petiole sealed with a pressure transducer in order to measure
      pressure transmission from the compressed gas (Pg) in the bomb to the xylem fluid
      (Px). Pressure bomb theory would predict a 1:1 relationship for Pg:Px when
      tobacco leaves start at a balance pressure of zero. Failure to observe the
      expected 1:1 relationship has cast doubt on the pressure-bomb technique in the
      measurement of the xylem pressure of plants. The experimental and theoretical
      relationship between Px and Pg was investigated in Tsuga canadensis (L) branches
      and Nicotiana rustica (L) leaves in this paper. It is concluded that the non 1:1
      outcome was due to the compression of air bubbles in embolized xylem vessels,
      evaporation of water from the tissue, and the expansion of the sealed stem
      segment (or petiole) protruding beyond the seal of the pressure bomb. The
      expected 1:1 relationship could be obtained when xylem embolism was eliminated
      and stem expansion prevented. It is argued that the non 1:1 relationship in the
      positive pressure range does not invalidate the Scholander pressure bomb method
      of measuring xylem pressure in plants because Px never reaches positive values
      during the determination of the balance pressure.

PMID- 10938838
TI  - A novel Arabidopsis thaliana dynamin-like protein containing the pleckstrin
      homology domain.
AB  - A full-length cDNA encoding a novel type of plant dynamin-like protein, ADL3, was
      isolated from Arabidopsis thaliana. ADL3 is a high molecular weight GTPase whose
      GTP-binding domain shows a low homology to those of other plant dynamin-like
      proteins. ADL3 contains the pleckstrin homology domain as is in mammalian
      dynamins, although other plant dynamin-like proteins reported lack this domain.
      The ADL3 gene was expressed weakly in various tissues, except for siliques with
      high level expression, which is distinct from the case for other plant dynamin
      like protein genes. Taken together, it is predicted that the mode of activation
      of ADL3 is different from those of other plant homologues.

PMID- 10938839
TI  - Modelling photosynthesis and its control.
AB  - The dynamic and steady-state behaviour of a computer simulation of the Calvin
      cycle reactions of the chloroplast, including starch synthesis and degradation,
      and triose phosphate export have been investigated. A major difference compared
      with previous models is that none of the reversible reactions are assumed to be
      at equilibrium. The model can exhibit alternate steady states of low or high
      carbon assimilation flux, with hysteresis in the transitions between the steady
      states induced by environmental factors such as phosphate and light intensity.
      The enzymes which have the greatest influence on the flux have been investigated
      by calculation of their flux control coefficients. Different patterns of control
      are exhibited over the assimilation flux, the flux to starch and the flux to
      cytosolic triose phosphate. The assimilation flux is mostly sensitive to
      sedoheptulose bisphosphatase and Rubisco, with the exact distribution depending
      on their relative activities. Other enzymes, particularly the triose phosphate
      translocator, become more influential when other fluxes are considered. These
      results are shown to be broadly consistent with observations on transgenic
      plants.

PMID- 10938840
TI  - Five ways to stay green.
AB  - The relationship between carbon income and expenditure over the life of a leaf is
      described and related to the productivity benefits of altering the timing of
      senescence initiation. In genetic variants with delayed leaf senescence ('stay
      greens') deconstruction of the photosynthetic apparatus during leaf senescence is
      partially or completely prevented. Although the staygreen phenotype is
      superficially similar in all species and genotypes, the genetic and physiological
      routes to the trait are diverse. In one type of stay-green, chlorophyll
      catabolism is disabled. Legumes and monocots with pigment breakdown lesions are
      discussed. Sorghum is presented as an example of another kind of stay-green in
      which perennial tendencies have been bred into a monocarpic annual crop species.
      Transgenic approaches are briefly discussed (enhanced endogenous cytokinins,
      reduced ethylene production or perception). An alternative route towards making a
      stay-green phenotype is through quantitative trait mapping and marker-assisted
      selection. Loci for greenness in pearl millet have been identified, some of which
      are associated with drought responses or flowering time. Finally the question of
      the limits on stay-green as a productivity-enhancing character is addressed.

PMID- 10938841
TI  - Control of C4 photosynthesis: effects of reduced activities of
      phosphoenolpyruvate carboxylase on CO2 assimilation in Amaranthus edulis L.
AB  - Heterozygous mutants of Amaranthus edulis deficient in PEP carboxylase (PEPC)
      have been used to study the control of photosynthetic carbon assimilation. A
      reduction in PEPC activity led to a decrease in the initial slope of the
      relationship between the CO2 assimilation rate and the intercellular CO2
      concentration and to a decrease in photosynthesis at high light intensities,
      consistent with a decrease in the capacity of the C4 cycle in high light. PEPC
      exerted appreciable control on photosynthetic flux in the wild-type, with a
      relatively high flux control coefficient of 0.35 in saturating light and ambient
      CO2. The flux control coefficient was decreased in low light or increased in low
      CO2 or in plants containing lower PEPC activity. However, the rate of CO2
      assimilation decreased down to about 55% PEPC, followed by an up-turn in the
      light-saturated photosynthetic rate as PEPC was further reduced, suggesting the
      existence of a mechanism that compensates for the loss of PEPC activity. The
      amounts of photosynthetic metabolites, including glycine and serine, also showed
      a biphasic response to decreasing PEPC. There was a linear relationship between
      the activity of PEPC and the activation state of the enzyme. A possible mechanism
      of compensation involving photorespiratory intermediates is discussed.

PMID- 10938842
TI  - Homeostasis of adenylate status during photosynthesis in a fluctuating
      environment.
AB  - This review describes and assesses pathways likely to influence and stabilize the
      ATP/reductant balance during whole cell photosynthesis. The sole reductive step
      of the Calvin cycle occurs during the conversion of 3-phosphoglycerate to triose
      phosphate. Photophosphorylation linked to this reaction can undoubtedly supply
      most of the ATP required by the Calvin cycle and other chloroplastic reactions.
      Small but crucial contributions must come from several other pathways, some of
      which involve co-operation between the chloroplast and the rest of the cell.
      Extrachloroplastic compartments can contribute to chloroplastic ATP requirements
      by supplying ATP directly or, probably more significantly, by accepting reducing
      equivalents and so supporting ATP synthesis within the chloroplast.

PMID- 10938843
TI  - Photosynthetic electron sinks in transgenic tobacco with reduced amounts of
      Rubisco: little evidence for significant Mehler reaction.
AB  - Transgenic tobacco (Nicotiana tabacum L. cv. W38) plants with an antisense gene
      directed against the mRNA of the small subunit of Rubisco were used to
      investigate the role of O2 as an electron acceptor during photosynthesis. The
      reduction in Rubisco has reduced the capacity for CO2-fixation in these plants
      without a similar reduction in electron transport capacity. Concurrent
      measurements of chlorophyll fluorescence and CO2 assimilation at different CO2
      and O2 partial pressures showed close linear relationships between chloroplast
      electron transport rates calculated from chlorophyll fluorescence and those
      calculated from CO2-fixation. These relationships were similar for wild-type and
      transgenic plants, indicating that the reduced capacity for CO2 fixation in the
      transgenic plants did not result in extra electron transport not associated with
      the photosynthetic carbon reduction (PCR) or photorespiratory carbon oxidation
      (PCO) cycle. This was further investigated with mass spectrometric measurements
      of 16O2 and 18O2 exchange made concurrently with measurements of chlorophyll
      fluorescence. In all tobacco lines the rates of 18O2 uptake in the dark were
      similar to the 18O2 uptake rates at very high CO2 partial pressures in the light.
      Rates of oxygenase activity calculated from 18O2 uptake at the compensation point
      were linearly related to the Rubisco content of leaves. The ratios of oxygenase
      to carboxylase rates were calculated from measurements of 16O2 evolution and 18O2
      uptake at the compensation point. These ratios were lower in the transgenic
      plants, consistent with their higher CO2 compensation points. It is concluded
      that although there may be some electron transport to O2 to balance conflicting
      demands of NADPH to ATP requirements, this flux must decrease in proportion with
      the reduced demand for ATP and NADPH consumption in the transgenic lines. The
      altered balance between electron transport and Rubisco capacity, however, does
      not result in rampant electron transport to O2 or other electron transport
      acceptors in the absence of PCR and PCO cycle activity.

PMID- 10938844
TI  - Transport of proteins into and across the thylakoid membrane.
AB  - The biogenesis of thylakoid proteins is a complex issue that requires the
      operation of at least four pathways within the chloroplast. Two of the pathways
      are used for soluble lumenal proteins, where the proteins bear cleavable
      targeting signals that are recognized by one of two distinct translocases. These
      pathways differ in fundamental respects. A subset of lumenal proteins are
      transported in an unfolded state by a typical Sec system, whereas others are
      transported by a novel class of translocase that appears to function primarily in
      the transport of fully-folded proteins. Related protein translocases have now
      been shown to operate in a wide variety of bacterial species, suggesting a
      widespread requirement for the translocation of folded proteins across biological
      membranes. Numerous integral membrane proteins are also targeted into the
      thylakoid membrane, and these too follow at least two distinct routes. Some
      proteins use a signal recognition particle-dependent pathway that requires GTP
      and unidentified apparatus in the thylakoid membrane. Others, however, require
      none of the known targeting factors and may insert spontaneously into the
      membrane. In this article, the rationale behind this pathway complexity is
      discussed in relation to the properties of the substrate proteins and the
      evolutionary origins of the chloroplast.

PMID- 10938845
TI  - The ycf 9 (orf 62) gene in the plant chloroplast genome encodes a hydrophobic
      protein of stromal thylakoid membranes.
AB  - There are still some open reading frames, orfs, with unknown function in the
      higher plant chloroplast genome. Of these conserved orfs, designated as ycfs
      (hypothetical chloroplast open reading frames), one is ycf 9 (orf 62) in the
      transcription unit with the psbC and psbD genes. The aim of this work was to
      investigate the function of ycf 9 by insertional inactivation of the gene with a
      selectable marker cassette, consisting of the aadA coding region connected to the
      trc promoter and rrnB terminator. This cassette was inserted 19 bp downstream
      from the start of the coding region of the tobacco ycf 9 gene. Two DNA constructs
      with the aadA cassette in opposite orientations were precipitated on 1 micron
      gold particles and delivered into leaves of Nicotiana tabacum, cultivar Samsun,
      by the biolistic method. Spectinomycin-resistant plants regenerated following
      bombardment with only the construct containing the aadA gene in the opposite
      orientation as ycf 9. In spite of several subsequent regeneration cycles on
      spectinomycin, the transplastomic plants did not reach homoplasmicity. This
      suggests that the ycf 9 gene product is essential for chloroplast function. Using
      a polyclonal antibody raised against the inner part of the gene product, the
      polypeptide was localized in the stromal thylakoid membranes of chloroplasts.

PMID- 10938846
TI  - Photosynthesis, plant growth and N allocation in transgenic rice plants with
      decreased Rubisco under CO2 enrichment.
AB  - Ribulose-1,5-bisphosphate carboxylase (Rubisco) efficiency for CO2-saturated
      photosynthesis was examined in leaves of rice (Oryza sativa L.). The amount of
      Rubisco in a leaf was calculated to be 30-55% in excess for the light-saturated
      rate of photosynthesis at 100 Pa CO2. Long-term exposure to CO2 enrichment
      decreased the amount of Rubisco protein. However, N was not reallocated from
      decreased Rubisco to other components limiting photosynthesis, and the decrease
      in Rubisco was simply due to a decrease in total leaf-N content by CO2
      enrichment. Thus, rice plants did not optimize N allocation into Rubisco at
      elevated CO2. Transgenic rice plants with decreased Rubisco were obtained by
      transformation with the rbcS antisense gene. The transformant with 65% wild-type
      Rubisco was selected as a plant with optimal Rubisco content for CO2-saturated
      photosynthesis at the level of a single leaf. This selected transgenic plant had
      20% lower rates of photosynthesis at normal CO2 (36 Pa), but 5-15% higher rates
      of photosynthesis at elevated CO2 (100 Pa) for a given leaf N content. However,
      such transgenic plants did not necessarily show greater production of biomass
      even under conditions of CO2 enrichment. Although they had a higher N-use
      efficiency for plant growth under such conditions during the middle stage of
      growth, the growth rate was lower during the early stage of growth. Thus,
      improvement of N-use efficiency by a single leaf did not necessarily lead to
      greater production of biomass by the whole plant.

PMID- 10938847
TI  - Is there scope for improving balance between RuBP-regeneration and carboxylation
      capacities in wheat at elevated CO2?
AB  - Carboxylation and RuBP-regeneration capacities, which determine light-saturated
      photosynthetic rate, were analysed in leaves of spring wheat (Triticum aestivum
      L. cv. Minaret) grown under different atmospheric CO2 partial pressure (pCa) and
      N supply regimes. Capacities were estimated from a large number of gas exchange,
      Rubisco and ATP-synthase content measurements, and from these, the pCa at which
      the two capacities are equal was derived, to allow direct comparison with growth
      pCa. Acclimation of the balance between the two capacities to growth at elevated
      pCa in wheat was only partial and appears to occur mostly in older flag leaves
      and at low N. However, in contrast to conclusions drawn from previous analyses of
      these data, there was evidence of a specific effect of growth at 70 Pa pCa, where
      carboxylation capacity is reduced more than RuBP-regeneration capacity for a
      given leaf N content. A model was used to estimate the effects of fluctuations in
      PPFD and temperature in the growth environment on the optimal balance between
      these capacities. This showed that the observed balance between carboxylation and
      RuBP-regeneration capacities in young wheat leaves could be consistent with
      adaptation to the current, or even the preindustrial pCa.

PMID- 10938848
TI  - Modelling the role of Rubisco activase in limiting non-steady-state
      photosynthesis.
AB  - The roles of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) and
      Rubisco activase in limiting the approach of photosynthesis to steady-state
      following a step increase from a low to a saturating value of photon flux density
      (PFD) are reviewed. This information, along with the effect of Rubisco on steady
      state photosynthetic rate and the effect of Rubisco activase on maximum Rubisco
      activation state, is then used to construct a model to predict the optimum
      allocation of protein between Rubisco and Rubisco activase for plants exposed to
      different light environments. The model predicts that the distribution of protein
      that produces the maximum steady-state rate of photosynthesis does not produce
      the maximum activation rate for Rubisco or the maximum steady-state activation
      state. The latter conclusion may explain why Rubisco is rarely found to be fully
      activated in leaves, even at saturating PFD values. The former suggests that
      plants exposed to fluctuating PFD should allocate more protein to Rubisco
      activase than plants exposed to constant PFD. This aspect of the model is
      explored in more detail for lightflecks of differing duration.

PMID- 10938849
TI  - Photosynthesis, sugars and the regulation of gene expression.
AB  - Sugar-mediated regulation of gene expression is a mechanism controlling the
      expression of many different plant genes. In this review, a compilation of the
      genes encoding photosynthetic proteins, subject to this mode of regulation, is
      presented. Several groups have devised different screening strategies to obtain
      Arabidopsis mutants in sugar sensing and signalling. An overview of these
      strategies has been included. Sugar-mediated regulation of gene expression is
      thought to require the hexokinase (HXK) protein. It has previously been shown
      that one such sugar, mannose, is capable of blocking germination in Arabidopsis.
      This inhibition is also mediated by HXK and occurs in the low millimolar
      concentration range. Here, the use of germination on mannose as an effective
      screening strategy for putative sugar sensing and signalling mutants is reported.
      T-DNA- and EMS-mutagenized collections were used to isolate 31 mannose
      insensitive germination (mig) mutants. With the use of these mutants, a
      comparison between this screen and other existing sugar-sensing screens is
      presented.

PMID- 10938850
TI  - Multiple paths of sugar-sensing and a sugar/oxygen overlap for genes of sucrose
      and ethanol metabolism.
AB  - The two-fold purpose of this work is, first, to review current hypotheses for
      multiple paths of sugar-sensing in an oxygen-responsive context, and second, to
      present evidence for the extent of sugar/oxygen overlap regulating genes for
      sucrose and ethanol metabolism. Current data indicate that sugar signals in
      plants may be initiated by (a) hexokinases, (b) membrane sensors, (c) acetate
      and/or respiratory metabolites, and (d) other signals and/or crosstalk. Responses
      may also involve concurrent input along transduction paths by effectors such as
      energy charge, P status, and phytohormones. Prime candidates for initiation
      and/or integration of such signal integration include SNF1- and SCF-like, multi
      enzyme complexes. In addition, different paths of sugar signal transduction may
      be linked to contrasting roles of responsive genes during feast, famine or
      pathogen attack. Oxygen can potentially alter sugar signals at several points, so
      its influence on feast and famine responses was initially tested with genes for
      sucrose metabolism in maize root tips. The Sus1 and Sh1 sucrose synthases in
      maize (typically up-regulated by carbohydrate abundance and deprivation,
      respectively) showed parallel responses to hypoxia (3% O2 [0.03l l-1 O2]) and
      anoxia (0% O2 [0l l-1 O2]) that were consistent with involvement of similar
      signals. In contrast, the differential sugar-responses of the lvr1 and lvr2
      invertases were not evident under low oxygen, and both genes were rapidly
      repressed. A third response was evident in the marked, sugar-regulation of an
      oxygen-responsive Adh1 gene for alcohol dehydrogenase, which was sensitive to
      sugar availability from deficit to abundance, regardless of oxygen status
      (anaerobic to fully aerobic [40% O2 (0.04l l-1 O2)]. A clear interface is thus
      evident between sugar and oxygen signals, but this varies markedly with the genes
      involved and probable differences in respective transduction paths.

PMID- 10938851
TI  - Ontogenetic changes of potato plants during acclimation to elevated carbon
      dioxide.
AB  - Transgenic potato plants (Solanum tuberosum cv. Desiree) with an antisense
      repression of the chloroplastic triosephosphate translocator were compared with
      wild-type plants. Plants were grown in chambers with either an atmosphere with
      ambient (400 mu bar) or elevated (1000 mu bar) CO2. After 7 weeks, the rate of
      CO2 assimilation between wild-type and transgenic plants in both CO2
      concentrations was identical, but the tuber yield of both plant lines was
      increased by about 30%, when grown in elevated CO2. One explanation is that
      plants respond to the elevated CO2 only at a certain growth stage. Therefore,
      growth of wild-type plants was analysed between the second and the seventh week.
      Relative growth rate and CO2 assimilation were stimulated in elevated CO2 only in
      the second and the third weeks. During this period, the carbohydrate content of
      leaves grown with elevated CO2 was lower than that of leaves grown with ambient
      CO2. In plants grown in elevated CO2, the rate of CO2 assimilation started to
      decline after 5 weeks, and accumulation of carbohydrates began after 7 weeks.
      From this observation it was concluded that acclimation of potato plants to
      elevated CO2 is the result of accelerated development rather than of carbohydrate
      accumulation causing down-regulation of photosynthesis. For a detailed analysis
      for the cause of the stimulation of growth after 2 weeks, the contents of
      phosphorylated intermediates of wild-type plants and transgenics were measured.
      Stimulation of CO2 assimilation was accompanied by changes in the contents of
      phosphorylated intermediates, resulting in an increase in the amount of
      dihydroxyacetone phosphate, the metabolite which is exported from the chloroplast
      into the cytosol. An increase of dihydroxyacetone phosphate was found in wild
      type plants in elevated CO2 when compared with ambient CO2 and in triosephosphate
      translocator antisense plants in ambient CO2, but not in the transgenic plants
      when grown in elevated CO2. These plants were not able to increase
      dihydroxyacetone phosphate further to cope with the increased CO2 supply. From
      these changes in phosphorylated intermediates in wild-type and transgenic plants
      it was concluded that starch and sucrose synthesis pathways can replace each
      other only at moderate carbon flux rates.

PMID- 10938852
TI  - Impact of elevated cytosolic and apoplastic invertase activity on carbon
      metabolism during potato tuber development.
AB  - During tuberization in Solanum tuberosum var. Desiree maximal catalytic
      activities of invertase(s) and sucrose synthase are inversely correlated. During
      the early stages, invertase activity is high and declines during maturation. The
      decrease in invertase activity is accompanied by a decrease in the hexose to
      sucrose ratio and an increase in sucrose synthase activity. This switch is
      paralleled by the onset of the storage phase as shown by the accumulation of
      starch and storage proteins. Biochemical and genetic evidence suggests that
      sucrose synthase activity is positively correlated with sink strength. To explore
      the possibility of enhancing sink strength in potato tubers by elevating the
      sucrolytic capacity, transgenic potato plants expressing either cytosolic or
      apoplastic yeast invertase in their tubers were made. Surprisingly, cytosolic
      invertase led to a decrease and apoplastic invertase to an increase in tuber
      yield. To understand the causes of the observed phenotypes, carbon metabolism in
      tubers of transgenic and control plants was analysed during different stages of
      tuber development. Both cytosolic and apoplastic invertase resulted in decreased
      sucrose and elevated glucose contents, indicating that sucrose is accessible in
      both compartments. Metabolic perturbation, however, was found to be compartment
      specific. Elevated cytosolic invertase activity led to increased carbon flux
      towards glycolysis and accumulation of phosphorylated intermediates. The
      phosphorylated intermediates were not used to build up starch. In contrast,
      apoplastic invertase does not lead to a significant increase in hexose phosphates
      compared to untransformed controls. Thus, hexoses originating in the apoplast are
      not efficiently phosphorylated during potato tuber development, which might be
      explained by an endocytotic uptake of sucrose and/or hexoses from the apoplast
      into the vacuole bypassing the cytosolic compartment.

PMID- 10938853
TI  - Selectable traits to increase crop photosynthesis and yield of grain crops.
AB  - The grain yield of cereals has almost doubled this century as a result of genetic
      manipulation by plant breeding. Surprisingly, there has been no change in the
      rate of photosynthesis per unit leaf area to accompany these increases. However,
      total photosynthesis has increased as a result of an increase in leaf area, daily
      duration of photosynthesis or leaf area duration. There remain substantial
      opportunities to continue to improve total photosynthesis and crop yield
      genetically using conventional breeding practices. Selectable traits are
      discussed here in the context of increasing total above-ground biomass under
      favourable conditions. Opportunities exist to alter crop duration and the timing
      of crop development to match it better to radiation, temperature and vapour
      pressure during crop growth, and to increase the rate of development of early
      leaf area to achieve rapid canopy closure. The importance of these traits will
      depend on the environment in which the crop is grown. Increases in crop
      photosynthesis through breeding are also likely to come via indirect means.
      Selection for a high and sustained stomatal conductance during the period of stem
      elongation is one way. Increasing assimilate allocation to the reproductive
      primordia so as to establish a large potential sink should also indirectly
      increase total crop photosynthesis. Evidence in the major grain crops suggests
      that by anthesis the capacity for photosynthesis is high and that photosynthesis
      is not limiting during grain filling. To use this surplus capacity it is
      suggested that carbon and nitrogen partitioning to the reproductive meristem be
      increased so as to establish a high potential grain number and the potential for
      a large grain size. It is then expected that additional photosynthesis will
      follow, either by a longer daily duration of photosynthesis or by an extended
      leaf area duration.

PMID- 10938854
TI  - Avenues for genetic modification of radiation use efficiency in wheat.
AB  - Radiation use efficiency (RUE) of a crop is a function of several interacting
      physiological phenomena, each of which can be tackled independently from the
      point of view of genetic improvement. Although wheat breeding has not raised RUE
      substantially, theoretical calculations suggest room for improvement. Selection
      for higher rates of leaf photosynthesis at saturating light intensities (Amax)
      has not resulted in improved RUE of crops, perhaps in part because most leaves in
      a canopy are not light-saturated. However, higher Amax may be observed as a
      pleiotropic effect of other yield-enhancing genes (e.g. genes for reduced
      height). Genetic transformation of Rubisco to double its specificity for CO2
      would theoretically increase Amax by perhaps 20%, and some evidence suggests that
      photosynthesis at sub-saturating light intensities would also be improved.
      However, photo-protection may be jeopardized if capacity for oxygenase activity
      is impaired. Photosynthetic rate of the whole eanopy can be enhanced by
      manipulation of leaf angle, which is under relatively simple genetic control, and
      possibly by manipulating leaf-N distribution throughout the canopy. Genetic
      diversity for adaptation of lower canopy leaves (e.g. changes in chlorophyll a:b
      ratio) to reduced light intensity observed in some crops needs to be investigated
      in wheat. Improved RUE may be achieved by increasing sink demand (i.e. kernel
      number) if excess photosynthetic capacity exists during grain filling, as
      suggested by a number of studies in which source-sink balance was manipulated.
      Some evidence suggests that improved sink strength may be achieved by lengthening
      the duration of the period for juvenile spike growth. Balancing source- and sink
      strength is a complex genetic challenge since a crop will change between source
      and sink limitation as conditions vary during the day, and with phenological
      stage. Improved RUE will be partly a function of a genotype's ability to buffer
      itself against changes in its environment to match the demand imposed by its
      development. Analysis of the physiological basis of genotype by environment
      interactions may indicate avenues for genetic improvement. The genetic control of
      photosynthetic regulation may be elucidated in the future through the application
      of genomics. However, given a lack of specific knowledge on the genetic basis of
      RUE, empirical selection is currently the most powerful tool for detecting
      favourable genetic interactions resulting from crosses between lines with
      superior photosynthetic traits and other high yielding characteristics. Selection
      for superior segregants can be accelerated using rapidly measured physiological
      selection traits, such as stomatal conductance or canopy temperature depression.

PMID- 10938855
TI  - Prospects for crop improvement through the genetic manipulation of
      photosynthesis: morphological and biochemical aspects of light capture.
AB  - The prospects for genetic manipulation of photosynthesis are assessed with an
      emphasis on the biochemical and morphological aspects of light capture. The
      connection between different parts of the photosynthetic process is considered
      together with the influence of environmental factors, development and
      acclimation, and metabolic regulation. The sites of real and potential
      photosynthetic losses are identified, using tropical rice as a case study. The
      important interaction between photosynthetic capacity, acclimation to the light
      environment, nitrogen accumulation and canopy architecture are discussed. The
      possibility of genetic intervention to increase both biomass accumulation and
      improve nitrogen economy simultaneously are considered. Finally, the numerous
      procedures for genetic manipulation of light harvesting are also discussed, with
      a view of improving radiation-use efficiency in crops.

PMID- 10938856
TI  - Transgenic approaches to crop improvement.
AB  - Transgenic crops are now grown commercially on several million hectares,
      principally in North America. To date, the predominant crops are maize (corn),
      soybean, cotton, and potatoes. In addition, there have been field trials of
      transgenics from at least 52 species including all the major field crops,
      vegetables, and several herbaceous and woody species. This review summarizes
      recent data relating to such trials, particularly in terms of the trends away
      from simple, single gene traits such as herbicide and insect resistance towards
      more complex agronomic traits such as growth rate and increased photosynthetic
      efficiency. Much of the recent information is derived from inspection of patent
      databases, a useful source of information on commercial priorities. The review
      also discusses the time scale for the introduction of these transgenes into
      breeding populations and their eventual release as new varieties.

PMID- 10938857
TI  - Chlorophyll fluorescence--a practical guide.
AB  - Chlorophyll fluorescence analysis has become one of the most powerful and widely
      used techniques available to plant physiologists and ecophysiologists. This
      review aims to provide an introduction for the novice into the methodology and
      applications of chlorophyll fluorescence. After a brief introduction into the
      theoretical background of the technique, the methodology and some of the
      technical pitfalls that can be encountered are explained. A selection of examples
      is then used to illustrate the types of information that fluorescence can
      provide.

PMID- 10938858
TI  - The control of ascorbic acid synthesis and turnover in pea seedlings.
AB  - The rate of ascorbate synthesis and turnover in pea seedling embryonic axes was
      investigated in relation to its pool size. Ascorbate accumulated in embryonic
      axes of germinating pea seeds which has been supplied with ascorbate.
      Incorporation of [U-14C]glucose into ascorbate after a 2 h labelling period was
      reduced by ascorbate loading for 3 h and 20 h, providing evidence that ascorbate
      biosynthesis is inhibited by endogenous ascorbate. Ascorbate turnover was
      estimated by following the metabolism of [1-14C]ascorbate over 2 h after
      ascorbate loading and by the rate of decrease of the ascorbate pool size after
      ascorbate loading. Ascorbate turnover rate, determined by [1-14C]ascorbate
      metabolism, increased as a linear function of pool size. The absolute turnover
      rate was higher in ascorbate-loaded embryonic axes but was always about 13% of
      the pool per hour. The initial rate of ascorbate turnover, estimated from the net
      decrease in pool size after ascorbate loading, also showed a similar turnover
      rate to that estimated from [1-14C]ascorbate metabolism. Ascorbate loading had no
      effect on ascorbate peroxidase, monodehydroascorbate reductase, dehydroascorbate
      reductase or glutathione reductase activity. Ascorbate oxidase activity decreased
      after ascorbate loading.

PMID- 10938859
TI  - An immunohistochemical study of the compartmentation of metabolism during the
      development of grape (Vitis vinifera L.) berries.
AB  - The compartmentation of key processes in sugar, organic acid and amino acid
      metabolism was studied during the development of the flesh and seeds of grape
      (Vitis vinifera L.) berries. Antibodies specific for enzymes involved in sugar
      (cell wall and vacuolar invertases, pyrophosphate: fructose 6-phosphate
      phosphotransferase, aldolase, NADP-glyceraldehyde-P dehydrogenase, cytosolic
      fructose 1,6-bisphosphatase), photosynthesis (Rubisco, fructose 1,6
      bisphosphatase, sedoheptulose 1,7-bisphosphatase), amino acid metabolism
      (cytosolic and mitochondrial aspartate aminotransferases, alanine
      aminotransferase, glutamate dehydrogenase, glutamine synthetase), organic acid
      metabolism (phosphoenolpyruvate carboxylase, NAD- and NADP-dependent malic
      enzyme, ascorbate peroxidase), and lipid metabolism (acetyl CoA carboxylase,
      isocitrate lyase) were used to determine how their abundance changed during
      development. There were marked changes in the abundance of many of these enzymes
      in both the flesh and seeds. The intercellular location of some enzymes was
      investigated using immunohistochemistry. Several enzymes (e.g.
      phosphoenolpyruvate carboxylase and those involved in amino acid metabolism) were
      associated with tissues likely to function in the transport of imported
      assimilates, such as the vasculature. Although other enzymes (e.g. NADP-malic
      enzyme and soluble acid invertase, involved in the metabolism of sugars and
      organic acids) were largely present in the parenchyma cells of the flesh, their
      distribution was extremely heterogeneous. This study shows that when considering
      the metabolism of complex structures such as fruit, it is essential to consider
      how metabolism is compartmentalized between and within different tissues, even
      when they are apparently structurally homogeneous.

PMID- 10938860
TI  - Mechanism of peroxidase actions for salicylic acid-induced generation of active
      oxygen species and an increase in cytosolic calcium in tobacco cell suspension
      culture.
AB  - Extracellularly secreted peroxidases in cell suspension culture of tobacco
      (Nicotiana tabacum L. cv. Bright Yellow-2, cell line BY-2) catalyse the salicylic
      acid (SA)-dependent formation of active oxygen species (AOS) which, in turn,
      triggers an increase in cytosolic Ca2+ concentration. Addition of horseradish
      peroxidase (HRP) to tobacco cell suspension culture enhanced the SA-induced
      increase in cytosolic Ca2+ concentration, suggesting that HRP enhanced the
      production of AOS. The mechanism of peroxidase-catalysed generation of AOS in SA
      signalling was investigated with chemiluminescence sensitive to AOS and electron
      spin resonance (ESR) spectroscopy, using the cell suspension culture of tobacco,
      and HRP as a model system of peroxidase reaction. The results showed that SA
      induced the peroxidase inhibitor-sensitive production of superoxide and H2O2 in
      tobacco suspension culture, but no production of hydroxy radicals was detected.
      Similar results were obtained using HRP. It was also observed that SA suppressed
      the H2O2-dependent formation of hydroxy radicals in vitro. The results suggest
      that SA protect the cells from highly reactive hydroxy radicals, while producing
      the less reactive superoxide and H2O2 through peroxidase-catalysed reaction, as
      the intermediate signals. The formation of superoxide was followed by that of
      H2O2, suggesting that superoxide was converted to H2O2. In addition, it was
      observed that superoxide dismutase-insensitive ESR signal of monodehydroascorbate
      radical was induced by SA both in the tobacco suspension culture and HRP reaction
      mixture, suggesting that SA free radicals, highly reactive against ascorbate,
      were formed by peroxidase-catalysed reactions. The formation of SA free radicals
      may lead to subsequent monovalent reduction of O2 to superoxide.

PMID- 10938861
TI  - Development of Fe-deficiency responses in cucumber (Cucumis sativus L.) roots:
      involvement of plasma membrane H(+)-ATPase activity.
AB  - One of the mechanisms through which some strategy I plants respond to Fe
      deficiency is an enhanced acidification of the rhizosphere due to proton
      extrusion. It was previously demonstrated that under Fe-deficiency, a strong
      increase in the H(+)-ATPase activity of plasma membrane (PM) vesicles isolated
      from cucumber roots occurred. This result was confirmed in the present work and
      supported by measurement of ATP-dependent proton pumping in inside-out plasma
      membrane vesicles. There was also an attempt to clarify the regulatory
      mechanism(s) which lead to the activation of the H(+)-ATPase under Fe-deficiency
      conditions. Plasma membrane proteins from Fe-deficient roots submitted to
      immunoblotting using polyclonal antibodies showed an increased level in the 100
      kDa polypeptide. When the plasma membrane proteins were treated with trypsin a 90
      kDa band appeared. This effect was accompanied by an increase in the enzyme
      activity, both in the Fe-deficient and in the Fe-sufficient extracts. These
      results suggest that the increase in the plasma membrane H(+)-ATPase activity
      seen under Fe-deficiency is due, at least in part, to an increased steady-state
      level of the 100 kDa polypeptide.

PMID- 10938863
TI  - A complex containing both trypsin inhibitor and dehydroascorbate reductase
      activities isolated from mitochondria of etiolated mung bean (Vigna radiata L.
      (Wilczek) cv. Tainan no. 5) seedlings.
AB  - A complex containing trypsin inhibitor (TI) activity was extracted with 0.1 M
      TRIS buffer (pH 7.9) from trypsin-treated mitochondria of etiolated mung bean
      seedlings, and further purified with a Superdex 200 FPLC column. This partially
      purified complex with an M(r) about 820 kDa exhibited additional dehydroascorbate
      (DHA) reductase activity with specific activities of 0.21, 1.53 and 1.54 mumol
      ascorbate formed min-1 mg-1 protein at pH 6.0, 6.5 and 7.0, respectively, when
      glutathione was added. Much lower DHA reductase activity (0.013 and 0.026 mumol
      ascorbate formed min-1 mg-1 protein at pH 6.5 and 7.0, respectively) was found
      when glutathione was omitted. The isolated complex gave positive results when it
      was tested by TI activity staining after SDS-PAGE, and could be recognized by a
      polyclonal antibody which was raised against 38 kDa sweet potato Kunitz-type TI,
      one of the root storage proteins of sweet potato. The possible physiological
      functions of this complex with both TI and DHA reductase activities were
      discussed.

PMID- 10938862
TI  - Phytochrome regulation of phytochrome A mRNA levels in the model short-day-plant
      Pharbitis nil.
AB  - The exposure of dark-grown Pharbitis nil seedlings to continuous R induces a
      rapid decrease in PHYA mRNA abundance with a half-life of about 2 h. A 5 min R
      pulse also induces this decline, and the effect is partially reversible by
      subsequent FR irradiation, confirming that the regulation of expression is
      mediated via the Pfr form of a phytochrome. When de-etiolated seedlings are
      returned to darkness after a W photoperiod, PHYA mRNA slowly reaccumulates from
      20% to 50% of the dark level within 24 h. The rate of reaccumulation is greatly
      accelerated by the removal of Pfr with a FR pulse, resulting in reaccumulation to
      100% within approximately 11 h. Without FR irradiation PHYA mRNA expression
      remains fully repressed for at least 11 h after the end of the photoperiod,
      suggesting that the controlling Pfr is highly stable.

PMID- 10938864
TI  - A Ca(2+)-dependent cysteine protease is associated with anoxia-induced root tip
      death in maize.
AB  - Imposition of anoxia on maize (Zea mays cv. B73) seedlings for 48 h or longer led
      to the death of the root tip. The necrosis extended into the root axis during
      postanoxic treatment, leading to the mortality of 30-50% of the seedlings. Using
      zymography, protease profiles in the root tissues of anoxic seedlings were
      studied. O2 deprivation for 24 h or longer repressed pre-existing protease
      activities and induced a novel soluble enzyme in the roots. The anoxia-induced
      protease (AIP) activity was predominant in the root apex at 24 h of anoxia and,
      subsequently, became the most abundant soluble activity in the root axis as well.
      The induction of AIP and its in vitro renaturation were Ca(2+)-dependent.
      Inhibitor sensitivity studies indicated that AIP is a cysteine protease. In SDS
      acrylamide gels, the enzyme activity migrated as a 23.5 kDa polypeptide. The
      anoxic induction of the activity was repressed by cycloheximide treatment,
      suggesting that new protein synthesis was required for the AIP appearance.
      Excision of the root tip (de-tipping) before anoxia led to a superior recovery of
      seedlings from stress injury. De-tipped seedlings showed lesser root damage and
      an increased production of lateral roots compared to intact seedlings.
      Furthermore, the superior anoxia tolerance of de-tipped seedlings was associated
      with a decreased AIP activity. Thus, the appearance of AIP activity in the root
      tip at 24 h of anoxia was spatially and temporally associated with the root
      tissue death. These studies further indicate that the root tip elimination early
      during anoxia may provide an adaptive advantage.

PMID- 10938866
TI  - Water stress enhances beta-amylase activity in cucumber cotyledons.
AB  - Cotyledons detached from 4-d-old cucumber (Cucumis sativus L.) seedlings were
      subjected to water stress (air-drying or PEG-treatment) to examine the effects of
      the stress on carbohydrate metabolism. Amylolytic activity in the cotyledon was
      increased about 6-fold by water stress within 1 d. The substrate specificity and
      the action pattern indicated that beta-amylase is responsible for the activity.
      Activities of azocaseinase, malate dehydrogenase and triose-phosphate isomerase
      were not affected by water stress, indicating that the effect of the stress on
      beta-amylase is rather specific. Cycloheximide-treatment strongly reduced the
      enhancement of beta-amylase activity. The hypocotyl of cucumber seedlings also
      exhibited an increase in the enzyme activity when subjected to water stress. The
      major free sugars in cucumber cotyledons were glucose, fructose, maltose, and
      sucrose; sucrose being the most abundant. Sucrose content in excised, unstressed
      cotyledons increased markedly during the incubation. Changes in other free sugars
      were small compared with that of sucrose. Starch also accumulated in unstressed
      cotyledons. In stressed cotyledons more sucrose and less starch accumulated than
      in unstressed ones. Such results were discussed in relation to the enhancement of
      beta-amylase activity.

PMID- 10938865
TI  - A glycoconjugate from corms of saffron plant (Crocus sativus L.) inhibits root
      growth and affects in vitro cell viability.
AB  - A glycoconjugate has been characterized from saffron corms (Crocus sativus L.)
      that inhibits the growth of roots of Nicotiana tabacum and Arabidopsis thaliana,
      at concentrations ranging from 1-100 micrograms m-3. Roots of seedlings grown in
      the presence 0.1 microgram m-3 glycoconjugate showed bulging of epidermal cells,
      whereas at 10 micrograms m-3, roots were completely devoid of hairs. At 100
      micrograms m-3 glycoconjugate the cell walls of the root vascular tissues were
      thicker and, overall, the vascular tissue was enlarged. In addition, this glycan
      is cytotoxic to isolated tobacco cells and protoplasts, with 50% cell death
      induced by 0.5 and 2 micrograms m-3 glycoconjugate, respectively. Morphological
      and biochemical changes induced by the exposure to the glycoconjugate included
      cell size decrease, loss of regular cell shape, cytoplasm collapse, and release
      of intracellular proteins. This molecule at low concentrations (0.1 microgram m
      3) mimics the effects of Yariv phenylglycosides and of mutant Arabidopsis which
      present defective or missing arabinogalactan-proteins (AGPs) in roots, indicating
      the glycoconjugate might interact with cell surface AGPs.

PMID- 10938867
TI  - Alterations in the plasma membrane polypeptide pattern of tomato roots
      (Lycopersicon esculentum) during the development of arbuscular mycorrhiza.
AB  - Changes induced by arbuscular mycorrhizal (AM) formation in the plasma membrane
      polypeptide pattern of tomato roots have been assessed by 2D-PAGE analysis.
      Plasma membrane fractions were isolated by aqueous two-phase partitioning from
      control and mycorrhizal tomato root microsomes. Analysis of 2D-PAGE gels revealed
      that AM colonization induces at the plasma membrane level two major changes in
      protein synthesis: down-regulation of some constitutive polypeptides and
      synthesis of new polypeptides or endomycorrhizins. A comparison of changes
      induced by two different levels of AM colonization showed that 16 polypeptides
      were differentially displayed at both AM colonization stages, while some others
      were transiently regulated. Five of the differentially displayed plasma membrane
      polypeptides at both AM colonization stages were selected for N-terminal amino
      acid sequencing. Reliable sequences were obtained for two of the selected spots.
      Sequence alignment search indicated that one of the sequenced polypeptides showed
      75% identity to the N-terminal sequence of the 69 kDa catalytic subunit of the
      vacuolar type H(+)-ATPase of several plants. The possible significance of these
      findings is discussed in relation to the functioning of the AM symbiosis.

PMID- 10938868
TI  - Mapping meristem respiration of Prunus persica (L.) Batsch seedlings: potential
      respiration of the meristems, O2 diffusional constraints and combined effects on
      root growth.
AB  - Root system architecture partially results from meristem activities, which
      themselves depend on endogenous and environmental factors, such as O2 depletion.
      In this study, meristem respiration and growth was measured in the root systems
      of three Prunus persica (L.) Batsch seedlings. The spatial distribution of
      meristem respiration within the root system was described, and the relationship
      between the respiration rates and meristem radii was analysed, using a model of
      radial O2 diffusion and consumption within the root. Histological observations
      were also used to help interpret the results. Respiration rates were linearly
      correlated to the root growth rates (rho 2 = 0.9). Respiration reached values
      greater than 3.5 x 10(-13) mol O2 s-1 for active meristems. The taproot meristem
      consumed more O2 than the rest of the entire root system meristems. Similarly,
      the first order lateral meristems used more O2 than the second order ones. A near
      hyperbolic relationship between respiration rates and meristem radii was
      observed. This can be explained by a model of radial O2 diffusion and consumption
      within the root. Therefore, only one maximum potential respiration rate and one
      O2 diffusion coefficient was estimated for all the meristems.

PMID- 10938869
TI  - Fluid ionic composition influences hydraulic conductance of xylem conduits.
AB  - The direct effect of fluid composition on xylem hydraulic conductance is
      investigated in excised stem segments of chrysanthemum (Dendranthema x
      grandiflorum Tzvelev cv. Cassa) plants. Dynamic changes in hydraulic conductance
      are accurately measured at 30 s intervals before and after modifications of the
      composition of the standard fluid (deionized water). It is investigated whether
      osmotic properties of the flowing solution influence overall hydraulic
      conductance by affecting the hydraulic conductance of vessel-to-vessel pit
      membranes, as has previously been suggested. Various iso-osmotic salt solutions
      (20 mOsm kg-1) of different composition raised the hydraulic conductance of 20 cm
      long stem segments approximately 5-8% compared to deionized water. In contrast,
      carbohydrate solutions with similar osmotic strength and pH did not cause any
      change in hydraulic conductance. KCl solutions that greatly differed in osmotic
      strength all increased hydraulic conductance, but the response was not correlated
      with the osmotic strength of the solution. Increasing the number of vessels that
      were open from one cut end to the other by shortening the stem segments greatly
      increased the hydraulic conductance response. Changing from deionized water to a
      salt solution caused an immediate increase in hydraulic conductance, while a
      shift back to deionized water resulted in a slow decline. This decline lasted
      longer when the salt solution contained divalent cations compared to monovalent
      cations. It is concluded that the presence of cations and not the osmotic
      strength in the flowing solution influenced the hydraulic conductance. The
      phenomenon is not caused by the vessel-to-vessel pit membranes, which in fact
      suppressed the effect, due to their large contribution to the overall resistance
      to water flow.

PMID- 10938870
TI  - Effects of short episodes of heat stress on flower production and fruit-set of
      groundnut (Arachis hypogaea L.).
AB  - Groundnuts (Arachis hypogaea L.) are an important crop of the semi-arid tropics
      where they are often exposed to maximum temperatures of > 40 degrees C for short
      periods during the growing season. The objectives of this study were to
      determine: (i) the effects of short periods of exposure to high temperature on
      flower production (FN), the proportion of flowers forming fruits (fruit-set) and
      the number of pegs and pods per plant (RNt); (ii) whether fruit-set is affected
      by high temperature during different periods of daylight in each diurnal cycle;
      and (iii) whether responses to temperature were qualitative or quantitative.
      Plants of cv. ICGV 86015 were grown in controlled environments at a day/night
      temperature of 28/22 degrees C from sowing until 9 d after flowering (DAF). Then,
      cohorts of plants were: (a) exposed to day temperature of 28, 34, 42 or 48
      degrees C for 2, 4 or 6 d; or were (b) exposed to 34, 42 or 48 degrees C for 6 d
      either throughout a 12 h day (08.00 to 20.00 h, WD), or only during the first 6 h
      (AM) or second 6 h (PM) of the day. Values of RNt were significantly reduced by
      high temperature, by duration of exposure, and by timing of exposure. Variation
      in FN was quantitatively related to floral bud temperatures during the day over
      the range 28-43 degrees C. In contrast, only floral bud temperatures > 36 degrees
      C during AM and WD significantly reduced fruit-set and hence RNt, whereas high PM
      temperature had no effect on fruit-set. These findings indicate that the response
      of RNt to day temperature is quantitative and can be modelled by combining the
      responses of FN and fruit-set to temperature.

PMID- 10938871
TI  - Regulation of alcoholic fermentation in coleoptiles of two rice cultivars
      differing in tolerance to anoxia.
AB  - To investigate regulation of anaerobic carbohydrate catabolism in anoxia-tolerant
      plant tissue, rate of alcoholic fermentation and maximum catalytic activities of
      four key enzymes were assessed in coleoptiles of two rice cultivars that differ
      in tolerance to anoxia. The enzymes were ATP-dependent phosphofructokinase (PFK),
      pyrophosphate-dependent phosphofructokinase (PFP), pyruvate decarboxylase (PDC),
      and alcohol dehydrogenase (ADH). During anoxia, rates of coleoptile elongation
      and ethanol synthesis were faster in the more tolerant variety Calrose than in
      IR22. Calrose coleoptiles, in contrast to IR22, also showed a sustained Pasteur
      effect, with the estimated rate of glycolysis during anoxia being 1.4-1.7-fold
      faster than that of aerobic coleoptiles. In Calrose after 5 d anoxia, maximum
      catalytic activities of crude enzyme extracts were (in mumol substrate g-1 fresh
      weight min.-1) 170-240 for ADH, 4-6 for PDC and PFP and 0.4-0.7 for PFK. During
      anoxia, activity per coleoptile of all four enzymes increased 3-5.5-fold,
      suggesting that PFK, and PFP, like PDC and ADH, are synthesised in anoxic rice
      coleoptiles. Enzyme activities, on a fresh weight basis, were lower in IR22 than
      in Calrose. In vivo activities of PDC and PFK in anoxic coleoptiles from both
      cultivars were calculated using in vitro activities, estimated substrate levels,
      cytoplasmic pH, and S0.5 (the substrate level at which 0.5Vmax is reached,
      without inferring Michaelis-Menten kinetics). Data indicated that potential
      carbon flux through PFK, rather than through PDC, more closely approximated rates
      of alcoholic fermentation. That PFK is an important site of regulation was
      supported further for Calrose coleoptiles by a decrease in the concentration of
      its substrate pool (F-6-P + G-6-P) following the onset of anoxia. By contrast, in
      IR22, there was little evidence for control by PFK, consistent with recent
      evidence that suggests substrate supply limits alcoholic fermentation in this
      cultivar.

PMID- 10938872
TI  - Computing factors of safety against wind-induced tree stem damage.
AB  - The drag forces, bending moments and stresses acting on stems differing in size
      and location within the mechanical infrastructure of a large wild cherry (Prunus
      serotina Ehrh.) tree are estimated and used to calculate the factor of safety
      against wind-induced mechanical failure based on the mean breaking stress of
      intact stems and samples of wood drawn from this tree. The drag forces acting on
      stems are calculated based on stem projected areas and field measurements of wind
      speed taken within the canopy and along the length of the trunk. The bending
      moments and stresses resulting from these forces are shown to increase
      basipetally in a nearly log-log linear fashion toward the base of the tree. The
      factor of safety, however, varies in a sinusoidal manner such that the most
      distal stems have the highest factors of safety, whereas stems of intermediate
      location and portions of the trunk near ground level have equivalent and much
      lower factors of safety. This pattern of variation is interpreted to indicate
      that, as a course of normal growth and development, trees similar to the one
      examined in this study maintain a cadre of stems prone to wind-induced mechanical
      damage that can reduce the probability of catastrophic tree failure by reducing
      the drag forces acting on older portions of the tree. Comparisons among real and
      hypothetical stems with different taper experiencing different vertical wind
      speed profiles show that geometrically self-similar stems have larger factors of
      safety than stems tapering according to elastic or stress self-similarity, and
      that safety factors are less significantly influenced by the 'geometry' of the
      wind-profile.

PMID- 10938873
TI  - Limiting CO2 levels induce a blue light-dependent HCO3- uptake system in
      Monoraphidium braunii.
AB  - The in situ photoactivation of an HCO3- uptake system in the green alga
      Monoraphidium braunii requires the irradiation of the cell suspensions with short
      wavelength radiation (blue, UVA and/or UVC). Plasma membrane ATPase inhibitors
      block the uptake of this monovalent anion at pH 9. M. braunii cells grown in high
      CO2 lack an HCO3- uptake system in their plasma membrane, but those grown in low
      CO2 can take up this anion at high rates. Cells grown in high CO2, transferred to
      CO2-limiting conditions in the light, start taking up HCO3- in 30 min, although
      they take 90 min to reach maximum rates of HCO3- transport. Therefore, this
      induction process seems to be triggered by low external CO2 concentration. In
      fact, increasing or decreasing the external HCO3- concentration does not induce
      the uptake system and only a decrease in CO2 concentration in the medium triggers
      the induction process. The appearance of the HCO3- transport activity is
      sensitive to cycloheximide, indicating that cytoplasmic protein biosynthesis is
      necessary for the induction of the uptake system. Photosynthetically active
      radiation, but not particularly blue light, is essential for induction of the
      uptake system to occur and the inhibition of photosynthesis by DCMU blocks it.
      From these results it can be inferred that when M. braunii cells detect a drop in
      CO2 concentration, they induce a blue light-dependent HCO3- uptake system.

PMID- 10938874
TI  - Differential expression of invertase genes in internal and external phloem
      tissues of potato (Solanum tuberosum L.).
AB  - The cloning of promoter sequences of two invertase genes from potato (Solanum
      tuberosum L.) is described. Histochemical analysis of series of reporter
      transgenic lines reveals phloem-specific expression from both promoters, with one
      expressed preferentially in internal phloem and the other in external phloem of
      stem vascular bundles.

PMID- 10938875
TI  - Plant hydraulic conductance measured by the high pressure flow meter in crop
      plants.
AB  - A new high pressure flow meter (HPFM) method for measuring plant hydraulic
      conductances (K) was investigated to examine whether its results are comparable
      to those from a conventional evaporative flux (EF) method in crops. Hydraulic
      conductance (K) was measured by the two methods under quasi-steady-state
      conditions in six crops grown in pots: soybean (Glycine max L. Merr. cv.
      Tsurunoko daizu), sunflower (Helianthus annuus L. cv. Russian mammoth), kidney
      bean (Phaseolus vulgaris L. cv. Tsurunashi morocco), tomato (Lycopersicon
      esculentum Mill. cv. Sekai-ichi), green pepper (Capsicum annuum L. cv.
      shishitou), and eggplant (Solanum melongena L. cv. Seiguro chunaga nasu). There
      was a 1:1 agreement between K values measured by the two methods for K values of
      whole plant, root and stem, and leaf under quasi-steady-state conditions. Leaf
      water potential (psi leaf) and evaporative flux density (E) in sunflower was
      curvilinear, indicating whole plant K estimated by the EF method increased with
      increase of E. Predicted psi leaf (= E divided by whole plant K measured by the
      HPFM method) agreed with measured psi leaf. Diurnal changes were also found in K
      measured by the HPFM confirming that K changed in response to temperature and E.
      The HPFM revealed that variable conductance was located in all organs: roots,
      stems, petioles, and leaves. These observations indicated that the HPFM is valid
      for crops as well as for trees (as previously established by Tsuda and Tyree) and
      has advantages over the EF method because of the speed and ease of the HPFM
      method.

PMID- 10938877
TI  - Investigation of a platelet factor 4 polymorphism on the immune response in
      patients with heparin-induced thrombocytopenia.
AB  - A small fraction of patients who receive heparin develop heparin-induced
      thrombocytopenia (HIT) and, of these patients, a still smaller proportion develop
      associated thrombotic complications. Heparin-induced thrombocytopenia is caused
      by the formation of antibodies that bind to specific complexes of platelet factor
      4 (PF4) and heparin. However, it remains uncertain why certain patients form
      these antibodies and develop HIT or why certain patients have thrombotic events.
      In this report we describe studies on individuals with and without HIT to
      determined if a potential PF4 polymorphism could explain differences in
      susceptibility to HIT. In the 10 control individuals and the 10 patients we
      studied, we did not find a difference in the PF4 sequences. Genetic difference in
      the PF4 antigenic target does not explain the occurrence of HIT in susceptible
      patients.

PMID- 10938876
TI  - Heat-shock proteins and platelet function.
AB  - Heat-shock proteins are found in organisms as diverse as slime moulds, bacteria,
      plants and higher eukarycotes. They play fundamental roles in cell function,
      ranging from protein folding to transmembrane protein movement, to serving as
      scaffolds or frameworks for the assembly of enzyme signalling complexes such as
      the steroid receptors. Intracellular concentrations may be high, in the range of
      structural proteins such as actin, with which they often interact. Therefore, it
      is not surprising that heat-shock proteins are present in blood platelets, and
      recent studies point to important roles in platelet function. The small heat
      shock protein, hsp27, becomes phosphorylated following cell stimulation with
      thrombin and associates with the actin-rich cytoskeleton. Phosphorylation results
      from activation of a protein kinase cascade involving the p38 mitogen-activated
      protein kinase (MAPK), the MAPKAP-K2 kinase, as well as PRAK, or p38-regulated
      protein kinase. Intriguingly, platelet hsp27 can associate with platelet factor
      XIII, suggesting a role for regulation of transglutaminase activity in
      stabilizing fibrin-platelet clots. The higher molecular-weight heat-shock
      proteins hsc70 and hsp90 are also present in platelets, being found in a large
      phosphorylated complex that contains the catalytic and myosin-targeting subunits
      of protein phosphatase 1 (PP1). Platelet adhesion to collagen via the alpha 2
      beta 1 integrin causes the rapid dissociation of this complex and
      dephosphorylation of components. These results suggest that hsc70 and hsp90 can
      serve as signalling scaffolds, helping regulate function, including platelet
      adhesion and spreading via modulation of protein phosphatase activity. Hsp27, on
      the other hand, may be more involved in controlling actin polymerization during
      the platelet shape change and subsequent aggregation.

PMID- 10938878
TI  - Shape change in human platelets: measurement with a channelyzer and visualisation
      by electron microscopy.
AB  - The increase in median platelet volume (MPV) that occurs following the addition
      of various agonists can be recorded by high-resolution channelyzers. However,
      this increase in MPV may not represent the platelet shape change (PSC), an early
      phase of platelet activation characterised by the formation of pseudopodia. We
      therefore compared the MPV after adding various agonists (serotonin, ADP or a
      thromboxane A2 analogue) with scanning electron micrographs (EM) of the platelets
      in the same sample. Saline alone did not increase the MPV or alter platelet
      morphology. In contrast, the selected agonists altered both the MPV and EM.
      Adrenaline (5.0 mumol/l) alone did not influence either of these indices of
      platelet activation. However, when a lower concentration of adrenaline (0.2
      mumol/l) was added in combination with a dose of serotonin (0.02 mumol/l) that
      did not affect the MPV on its own, the measured MPV increased significantly and
      the EM showed pseudopodia formation. Because the channelyzer method is
      reproducible and suited to serial measurements of the MPV, it may become a useful
      tool for the investigation of platelet activation.

PMID- 10938880
TI  - Use of a platelet filter test in patients with thrombocytosis.
AB  - In the differential diagnosis of primary and secondary thrombocytosis platelet
      function tests may play an important role. We examined the applicability of a
      platelet filter test (shear-dependent platelet aggregation) as a tool, to
      differentiate primary thrombocytosis (cases with myeloproliferative disorders)
      from secondary (reactive) thrombocytosis. The test was carried out in 53 patients
      suffering from myeloproliferative disorders associated with primary
      thrombocytosis and in 21 patients with other diseases complicated by secondary
      thrombocytosis. Using citrate as anticoagulant, the sensitivity of the O'Brien's
      test proved to be 77.1%, and its specificity 94.4%. Using heparin as
      anticoagulant the sensitivity and specificity of the test were found to be also
      reliably high. Based on these studies we suggest the use of the O'Brien's
      filterometer as a screening test in the differential diagnosis in patients with
      elevated platelet count. In the case of normal results, the causes of reactive
      thrombocytosis should be clarified first, while with abnormal results,
      haematological examination of the patients should be performed.

PMID- 10938879
TI  - Quantitative detection of platelet aggregates in whole blood without fixation.
AB  - Platelet counting detects lesser degrees of platelet aggregation than
      conventional aggregometry. In order to prevent progressive platelet aggregation
      or disaggregation after sampling it is customary to fix blood samples. However
      fixation may introduce other artefacts. We first compared stability of platelet
      counts in EDTA-, citrate- and r-hirudin-anticoagulated blood from healthy
      volunteers. Second, the stability of platelet counts in unfixed EDTA- and hirudin
      anticoagulated blood was compared with glutaraldehyde-fixed blood in the same
      anticoagulants. Third, the effect of in vivo heparin administration on platelet
      counts in EDTA- and hirudin-anticoagulated blood was studied. Platelet counts
      within 2 h of collection were significantly higher in EDTA- than in hirudin- or
      citrate-anticoagulated blood (P = 0.002 vs. hirudin and P = 0.001 vs. citrate).
      Twenty-four hour counts in hirudin and EDTA were unchanged (P = 0.3 and P = 0.2,
      respectively, vs. earlier counts). Counts in citrate increased significantly (P =
      0.007; n = 10). Platelet counts in fixed blood did not differ significantly from
      those in unfixed blood. Heparin administered for cardiopulmonary bypass reduced
      platelet counts in hirudin-anticoagulated blood from (mean +/- 1 standard
      deviation) 180 +/- 45 to 162 +/- 30 x 10(9) l-1 (P = 0.01; n = 14), without
      significantly lowering counts with EDTA-anticoagulation, consistent with
      increased platelet aggregation. Hirudin and EDTA provided stable platelet counts,
      suggesting that fixation is unnecessary.

PMID- 10938882
TI  - EDTA-induced changes in platelet structure and function: clot retraction.
AB  - Ethylenediamine tetracetic acid (EDTA) is known to cause structural, biochemical
      and functional injury to blood platelets, including irreversible dissociation of
      the fibrinogen receptor, glycoprotein alpha IIb beta 3 (GPIIb/IIIa). Despite
      inability to adhere to glass, spread, and to aggregate in response to adenosine
      diphosphate (ADP) and other agonists, EDTA-treated platelets support clot
      retraction as well as untreated cells. The present study has used clot retraction
      under isometric tension and electron microscopy to determine if there are any
      differences in platelet-fibrin interactions of clots formed from blood collected
      in EDTA or platelets from blood drawn into citrate (CCD) anticoagulants. No
      physical differences could be identified. Polymerizing fibrin bound intimately to
      aggregates developing from EDTA platelets undergoing shape change, internal
      transformation, adhesion and spreading on fibrin strands oriented in the long
      axis of contraction. The results suggest that reassociation of irreversibly
      dissociated GPIIb/IIIa takes place immediately after initiation of clot
      retraction, or that a significant proportion of GPIIb/IIIa receptors on resting
      platelets are inaccessible to EDTA and become available after activation by
      thrombin.

PMID- 10938881
TI  - Effect of aspirin on platelet desaggregation induced by SR121566, a potent GP
      IIb/IIIa antagonist.
AB  - Since results of recent clinical trial, performed in patients suffering from
      acute coronary syndromes, suggested that aspirin improved the efficacy of an anti
      GP-IIb/IIIa therapy, this work was set to study the mechanism underlying such a
      mechanism of aspirin. SR121566 (3 mg/kg, i.v.), a new selective antagonist of the
      GP-IIb/IIIa complex inhibited thrombus formation which occurred following
      electrical stimulation of the carotid artery of rabbits. On rabbits pre-treated
      with aspirin (10 mg/kg, i.v.), a bolus injection of SR121566 produced a strong
      reversal of thrombosis compared with the effect obtained on rabbits treated with
      SR121566 alone. In vitro, the addition of SR121566 to human platelets during the
      ADP-induced aggregation process resulted in a reversal of the aggregation which
      was nearly complete when it was added 30 s after the induction of aggregation,
      but progressively decreased when SR121566 was added at later times. ADP-induced
      platelet aggregation in the presence of aspirin (1 mM) was comparable to that
      obtained in control platelet-rich plasma, but the addition of SR121566 at all
      time points of the aggregation process was followed by a complete reversal of the
      aggregation even at later time points (> 120 s). Histological examination of the
      platelet aggregates showed a clear-cut difference in the platelet content between
      control and aspirin-treated platelets which contained much more dense granules.
      Inhibition of the release of thrombospondin by aspirin may account for a
      significant part of its pro-desaggregating activity as demonstrated by the effect
      of the tetrapeptide VTCG, an inhibitor of the binding of thrombospondin to its
      receptor, which strongly potentiated the activity of SR121566 as a desaggregating
      agent. Therefore, our study shows that aspirin pretreatment promotes a
      'thrombolytic' activity of GP-IIb/IIIa inhibitors and, in particular, of
      SR121566, a potent and selective member of this new class of compounds. This
      effect is mainly due to an inhibition of the release of the platelet granule
      content and in particular to thrombospondin. This observation may contribute to a
      greater efficacy of GP-IIb/IIIa inhibitors for the treatment of thrombosis in
      atherosclerotic patients.

PMID- 10938883
TI  - EDTA-induced changes in platelet structure and function: adhesion and spreading.
AB  - Ethylenediamine tetraacetic acid (EDTA) is an effective anticoagulant, but
      unfortunately causes structural, biochemical and functional damage to human
      platelets. Some of the functional injuries, such as adhesion to and spreading on
      surfaces, are considered irreversible. The present investigation has evaluated
      that hypothesis. Our findings indicate that platelets from EDTA platelet-rich
      plasma (PRP) or CCD PRP to which EDTA has been added do not adhere to glass or
      plastic surfaces. However, when platelets from EDTA PRP or CCD PRP containing
      added EDTA are washed and resuspended under conditions reported to cause
      irreversible dissociation of the fibrinogen receptor, GPIIb/IIIa, then washed and
      resuspended in buffer containing Ca2+ and Mg2+ ions will adhere and spread in the
      same manner as platelets not exposed to EDTA. The ability to recover adhesive
      function may explain why EDTA platelets are able to sustain clot retraction as
      well as CCD platelets.

PMID- 10938884
TI  - PI 3-kinase signalling in platelets: the significance of synergistic, autocrine
      stimulation.
AB  - Phosphoinositide 3-kinases (PI 3Ks) play a key role in regulation of
      intracellular signalling and cellular function, including cell proliferation,
      apoptosis, chemotaxis, membrane trafficking and platelet activation. The PI 3Ks
      are grouped into three classes on the basis on their structure and in vitro
      substrate specificity. Class I are activated by a variety of agonists which
      mediate their effect through tyrosine kinase-linked or G-protein-linked
      receptors. In vivo class I PI 3Ks seem to preferentially phosphorylate the D3
      hydroxyls of the inositol moiety of PtdIns(4,5)P2 to produce PtdIns(3,4,5)P3.
      However, class II PI 3Ks preferentially phosphorylate the D3 hydroxyl of PtdIns
      and PtdIns(4)P to produce PtdIns(3)P and PtdIns(3,4)P2, respectively. The late
      accumulation of PtdIns(3,4)P2 has been suggested to play an important role in
      irreversible platelet aggregation. In human platelets the class II PI 3K isoform
      HsC2-PI 3K is activated in an integrin alpha IIb beta 3 + fibrinogen-dependent
      manner. Class III PI 3Ks phosphorylate PtdIns to produce PtdIns(3)P, which play a
      crucial role in vesicular trafficking. Recent work has suggested that crosstalk
      between individual receptors and their downstream signal pathways play a central
      role in PI 3K signalling responses. In this review, we will concentrate on recent
      advances regarding the regulation of platelet PI 3Ks.

PMID- 10938885
TI  - Inhibition of induced and spontaneous platelet aggregation by destabilase from
      medicinal leech.
AB  - Destabilase, endo-epsilon-(gamma-Glu)-Lys isopeptidase from the medicinal leech,
      inhibits arterial thrombus formation in rats. Inhibition of platelet aggregation
      was supposed to be one of the main mechanisms of this phenomenon. To elucidate
      this question highly purified destabilase preparations were used. Aggregation was
      monitored both by a turbidometric method and by a method based on real-time
      estimation of mean aggregate size. Spontaneous aggregation of human platelets was
      completely blocked by destabilase. At 5 microM ADP maximal inhibition was 63%.
      Aggregation induced by PAF (100 nM) and collagen (0.1 mg/ml) was inhibited in the
      presence of destabilase by 50 and 65%, respectively. This enzyme does not
      activate adenylate cyclase but inhibits it. We suggest that destabilase interacts
      with high-affinity binding sites on the platelet plasma membrane, thus providing
      an anti-aggregating effect. This idea coincides with the data that destabilase
      primary structure has high homology with some adhesive proteins.

PMID- 10938886
TI  - Blood irradiation by He-Ne laser induces a decrease in platelet responses to
      physiological agonists and an increase in platelet cyclic GMP.
AB  - The effect of He-Ne laser irradiation on platelet adhesion, activation and
      aggregation was investigated. Citrated whole blood was irradiated in vitro by He
      Ne laser (632.8 nm, 7 mW) and then subjected to shear stress (1300 s-1) on
      subendothelial extracellular matrix (ECM)-coated plates. Laser irradiation was
      followed by a decrease in platelet adhesion and aggregation on ECM under flow
      conditions in a time exposure-dependent manner (by 30-40%). The inhibiting effect
      of laser light on platelets was detectable up to 1 h after the termination of
      irradiation. Laser irradiation of either platelet-rich plasma, gel-filtered
      platelets, platelet-poor plasma, or packed blood cells followed by whole blood
      reconstitution revealed a marked decrease in platelet deposition on ECM only in
      the cases of platelet-rich plasma or gel filtered platelets. In conventional
      aggregometry, laser-treated platelet-rich plasma demonstrated a diminished
      platelet response to both thrombin receptor-activating peptide (TRAP), converting
      a two-wave aggregation curve to reversible, and to the protein kinase C activator
      PMA (by 45%). In flow cytometry analysis, irradiated platelets presented lower
      fibrinogen binding and P-selectin expression in response to TRAP. Laser
      irradiation had no additional inhibitory effect on dibutyryl cGMP- and dibutyryl
      cAMP-pretreated platelets. A 50% increase in cGMP level was observed in laser
      treated gel filtered platelets, both in the presence and in absence of the
      phosphodiesterase inhibitor, isobuthylmethylxanthine. The results suggest that
      guanylate cyclase is one of the primary mediators of the laser effect on platelet
      function.

PMID- 10938887
TI  - Influence of auto-antibody specificities on the clinical course in patients with
      chronic and acute ITP.
AB  - It is now well established that the target antigens of platelet auto-antibodies
      are the GP IIb/IIIa and GP Ib/IX receptors. In our study, it was observed that
      the majority of patients had antibodies directed towards the GP IIb/IIIa
      receptor, whereas the number of patients having antibodies directed towards the
      GP Ib/IX receptor was much less. Also, we found that the patients in whom the
      auto-antibodies are directed towards the GP IIb/IIIa receptors usually have mild
      bleeding. On the other hand, the patients having auto-antibodies directed towards
      both GP IIb/IIIa and GP Ib/IX receptors have a severe bleeding diathesis, and
      usually show poor prognosis to treatment with corticosteroids.

PMID- 10938888
TI  - Glycoprotein IIb-IIIa-liposomes bind fibrinogen but do not undergo fibrinogen
      mediated aggregation.
AB  - Although platelet cross-bridging is mediated primarily by the binding of
      fibrinogen to its activated membrane receptor, glycoprotein (GP) IIb-IIIa*, such
      an interaction may not be sufficient to support the aggregation process. As this
      question could potentially be answered by reconstituting GPIIb-IIIa* into a non
      platelet environment such as liposomes, a protocol was developed for the
      generation of large lipid vesicles containing purified GPIIb-IIIa*. Flow
      cytometric techniques confirmed that the receptor was present in the lipid
      bilayer and were used to evaluate the characteristics of fibrinogen binding to
      the liposomes, which like fibrinogen-platelet interactions exhibited specificity,
      saturability, time dependence and calcium dependence. No fibrinogen-specific
      aggregation of GPIIb-IIIa* liposomes with stir or shear was observed, as
      determined by flow cytometric cell counting and microscopic examination of
      particles. In contrast, activated platelets rapidly bound Fg and rapidly formed
      large aggregates. The Fg associated with GPIIb-IIIa* in liposomes was 'normally'
      recognized by two fluorescently labelled antibodies: 4A5, which interacts with
      the Fg gamma chain C-terminus (residues 400-411) required for Fg-mediated cross
      bridging of activated platelets in platelet aggregation (Shiba E, Lindon JN,
      Kushner L, Matsueda GR, Hawiger J, Kloczewiak M, Kudryk B, Salzman EW. Antibody
      detectable changes in fibrinogen adsorption affecting platelet activation on
      polymer surfaces. Am J Physiol 1991; 260: C965-74), and anti-Fg-RIBS-I, which
      associates with an epitope on Fg (residues 373-385) expressed upon binding to
      GPIIb-IIIa. These data suggest that the Fg gamma-terminus is sterically
      accessible for particle cross-bridging and that an identical conformational
      change occurs for receptor-bound Fg on both liposomes and platelets. It thus
      appears that cellular elements aside from GPIIb-IIIa, such as cytoskeletal
      proteins proposed to be necessary for receptor 'anchoring', play a necessary role
      in flow-associated platelet aggregation.

PMID- 10938889
TI  - Platelet dysfunction detected at high shear in patients with heart valve disease.
AB  - Whether patients with valvular heart disease have a defect of platelet function
      has been unclear. Despite evidence that these individuals have an abnormality
      detectable only under conditions of high shear stress, no methods have been
      widely available to adequately assess platelet function under such conditions.
      The Platelet Function Analyzer (PFA)-100 measures platelet function in a high
      shear environment and is well suited to the detection of platelet dysfunction in
      the clinical laboratory. The instrument records the time for platelets to occlude
      a membrane coated with collagen and either epinephrine (CEPI) or ADP (CADP). We
      studied the PFA-100 in 398 patients before open heart surgery; 308 for coronary
      artery bypass grafting (CABG) and 90 for aortic or mitral valve replacement (VR).
      Patients were classified as normal (CEPI < or = 153 s); 'aspirin effect' (CEPI >
      153 s but CADP < or = 109 s) or abnormal (CEPI > 153 s and CADP > 109 s). In the
      CABG group, 41.2% were classified as normal, 43.2% as 'aspirin effect' and 15.6%
      as abnormal. In contrast, in patients undergoing VR, these values were 6.7, 11.1
      and 82.4%, respectively. Patients with valvular disease had significantly longer
      closure times for both CEPI and CADP tests (P < 0.001). In addition, the valvular
      disease group had a significantly higher proportion of patients with markedly
      prolonged (> 150 s) closure times in the CADP cartridge (43.3 vs. 3.6%,
      respectively). Only one (0.3%) patient in the CABG group had non-closure (> 300
      s) in the CADP test compared to seven (7.8%) in the valvular disease group. Three
      of six patients in the latter group bled excessively during surgery. We conclude
      that abnormal CADP closure is much more frequent among patients with aortic or
      mitral valve disease compared to those with coronary artery disease. This may
      reflect pre-existing high-shear damage to platelets that renders them refractory
      to subsequent shear activation and aggregation in the PFA-100 system. Further
      studies are needed to more precisely define the platelet defect in these
      patients. Markedly prolonged CADP closure in patients with valvular disease may
      indicate an increased likelihood of intra-operative bleeding, although an
      appropriately designed prospective study is needed to adequately address this
      hypothesis.

PMID- 10938890
TI  - Blood platelet activation evaluated by flow cytometry: optimised methods for
      clinical studies.
AB  - A variety of flow cytometry techniques are in use to evaluate in vivo blood
      platelet activation. We have in this study further developed and optimised these
      methods to be suitable for use in clinical studies. By preloading the Monovette
      EDTA vacuum blood sampling tubes with 1/8 vol 4% (w/v) paraformaldehyde (PFA), we
      were able to assess platelet CD62P (P-selectin) expression in whole blood with
      less than 0.2% activated platelets. No washing or neutralising steps were
      required to remove excess fixative. Both basal and agonist-stimulated CD62P
      expression were stable for at least 48 h after sampling. The standard curve was
      linear from 1.9 (basal) to 8.1 x 10(3) (TRAP-stimulated) molecules of equivalent
      soluble fluorochrome units (MESF) in phycoerythrein-conjugated anti-CD62P
      labelled whole blood samples. These assay conditions were also well suited for
      assessment of platelet expression of CD41, CD42a, CD61 and CD63. The preanalytic
      storage period was extended from 10 min to at least 2 h for platelet PAC-1 and
      fibrinogen binding analysis by preloading Monovette citrate tubes with 8/10 vol
      buffer. With PFA preloading, blood sampled into citrated tubes could be analysed
      for fractions of microparticles and platelet-platelet aggregates as well as for
      aggregate size.

PMID- 10938891
TI  - Evaluation of circulating platelet-leukocyte conjugates: a sensitive flow
      cytometric assay well suited for clinical studies.
AB  - Circulating platelet-leukocyte conjugates are found in patients with a variety of
      diseases. We have developed a flow cytometry-based assay for monitoring the
      presence of such conjugates. By preloading the sampling tubes with 1/8 volume of
      4% paraformaldehyde, basal levels of platelet-leukocyte conjugates was stable for
      at least 48 h after blood sampling. The leukocytes were discriminated from the
      other cells in fixed whole blood by binding of anti-CD45, and no lysing, washing,
      or centrifugation steps were required. In whole blood from healthy individuals,
      platelets were found adherent to 3.2% of the lymphocytes, 4.1% of the monocytes
      and to 2.5% of the granulocytes. The corresponding values for mean number of
      platelets per leukocyte were 1.3 x 10(-2), 2.5 x 10(-2) and 1.6 x 10(-2),
      respectively. Upon in vitro agonist (ADP, TRAP) stimulation, the platelet
      adhesion to monocyte and granulocytes increased several-fold. Microscopy verified
      the flow cytometry results and revealed that platelet adhered to the leukocytes
      as platelet-platelet aggregates and not as single platelets as the agonist
      concentration increased. At high concentrations of TRAP, the strong agonist,
      large multiconjugates with several granulocytes per platelet-platelet aggregate
      evolved. Being an assay well suited for clinical studies, the recommended
      approach may be a valuable tool in establishing the clinical significance of
      circulating platelet-leukocyte conjugates.

PMID- 10938892
TI  - An investigation of the serotonergic effects of fenfluramine, dexfenfluramine and
      dexnorfenfluramine using platelets as neuronal models.
AB  - The appetite-suppressant, fenfluramine (d,l-F) has been used for several decades
      to treat obesity. Dexfenfluramine (d-F), the d-enantiomer of d,l-F, was approved
      in 1996 for long-term administration. Subsequently, these drugs were voluntarily
      withdrawn due to reports of adverse effects on heart valves. So far, the evidence
      regarding the serotonergic action of d,l-F and d-F has relied on animal-based
      experiments. We used human platelets as neuronal models to assess the
      serotonergic action of both d,l-F, d-F and the main metabolite of d-F, d
      norfenfluramine (d-norF). This was evaluated using a sensitive method that
      assesses platelet shape change (PSC) as expressed by an increase in median
      platelet volume (MPV). Human platelets increased their MPV in response to d-norF.
      This action was probably mediated via serotonin (subtype 2) receptors because a
      specific antagonist blocked it. This is the first demonstration, using human
      tissue, of the serotonergic action associated with the administration of d-F.

PMID- 10938893
TI  - Translational regulation of platelet-derived growth factor B chain (c-sis) mRNA
      by short open reading frames in the 5'-untranslated region.
AB  - Platelet-derived growth factor B chain (PDGF-B/c-SIS), the product of c-sis proto
      oncogene, is a potent mitogen and chemoattractant for cells of mesenchymal
      origin. Expression of PDGF-B/c-SIS is regulated at the translational level, in
      addition to at the transcriptional level. The 5'-untranslated region (5'-UTR) of
      PDGF-B/c-sis mRNA is known to inhibit translation of the downstream coding
      sequences. The 5'-UTR contains putative influential elements, such as GC-rich
      elements, stem-loop structures and short open reading frames (SORFs). To clarify
      the inhibition mechanism of PDGF-B/c-sis mRNA translation, effects of three SORFs
      in the 5'-UTR on the translational regulation were investigated in transient
      expression assays. Introducing point mutation(s) in the initiation codons of
      SORFs affected the reporter gene expression in several cell lines (COS-1, U-2,
      JEG-3). Abrogation of three SORFs resulted in an increase of the reporter gene
      expression both in beta-galactosidase assay and Western blot analysis. These
      results suggest that SORFs in the 5'-UTR sequences have inhibitory effects on the
      translation of the downstream coding sequences.

PMID- 10938894
TI  - Activation of protein-tyrosine kinase pathways in human platelets stimulated with
      the A1 domain of von Willebrand factor.
AB  - The binding of multimeric von Willebrand Factor (vWF) to its specific receptor on
      platelets, glycoprotein (GP)Ib, is a critical event, allowing platelet activation
      and subsequent thrombus formation in the vessels. In this study, the effects of
      the monomeric A1 domain, which contains the GPIb-binding site of the vWF
      molecule, on platelet activation were examined. The binding of the A1 domain to
      GPIb resulted in Syk activation and association with Src, as is the case with
      intact vWF. However, the A1 domain, in contrast to vWF, did not induce platelet
      cytoskeletal association of tyrosine kinases, Src and Lyn. When platelet
      functional responses, such as aggregation and intracellular Ca2+ mobilization,
      were monitored, the A1 domain failed to induce the responses by itself and
      blocked the responses induced by the multimeric vWF molecule. These results
      suggested that the A1 domain triggers at least some of tyrosine kinase-related
      signals via GPIb and may be a partial agonist as well as a competitive antagonist
      for the vWF-GPIb interaction.

PMID- 10938896
TI  - Increased leukocyte-platelet adhesion in chronic myeloproliferative disorders
      with high platelet counts.
AB  - The heterophilic adhesions between monocytes and platelets may result in the
      modification of both platelet and monocyte function. This mutual modification
      includes a greater activation of platelets with increased production of PDGF and
      other metabolites as well as an enhanced tissue factor expression of monocytes
      with greater activity in the circulation. The heterophilic aggregation has been
      well documented during extracorporal circulation, haemodialysis and in diabetic
      retinopathy. Here we provide evidence that there is significant increase of
      monocyte-platelet aggregates in disorders associated with high platelet counts,
      such as chronic myeloproliferative disorders. The presence of these heterophilic
      aggregates may contribute to the vascular complications observed frequently in
      polycythaemia vera and essential thrombocythaemia.

PMID- 10938895
TI  - Habitual smoking causes an abnormality in platelet thromboxane A2 metabolism and
      results in an altered susceptibility to aspirin effects.
AB  - The present study investigates the effects of aspirin (100 mg every second day
      for 14 days) on platelet function in nine healthy non-smokers and in nine healthy
      habitual smokers. There was a significantly (P < 0.05) stronger inhibition of
      collagen (0.6 microgram/ml)- and ADP (2 microM)-induced platelet aggregation by
      aspirin in smokers as compared to non-smokers. This difference occurred in the
      presence of an almost complete (> 95%) inhibition of thromboxane A2 (TXA2)
      synthesis in both groups. The platelet capacity to generate TXA2 in vitro was
      significantly reduced in smokers, urinary excretion of TXA2, however, was
      significantly increased. Thus, the better susceptibility of smokers to anti
      aggregatory effects of aspirin is very likely to be related to a chronic smoking
      induced alteration of platelet TXA2 system. Cessation of smoking should,
      therefore, be encouraged.

PMID- 10938897
TI  - Calpain regulation of integrin alpha IIb beta 3 signaling in human platelets.
AB  - Efficient platelet adhesion and aggregation at sites of vascular injury requires
      the synergistic contribution of multiple adhesion receptors. The initial adhesion
      of platelets to subendothelial matrix proteins involves GPIb/V/IX and one or more
      platelet integrins, including integrin alpha IIb beta 3, alpha 2 beta 1, alpha 5
      beta 1 and possibly alpha 6 beta 1. In contrast, platelet-platelet adhesion
      (platelet cohesion or aggregation) is mediated exclusively by GPIb/V/IX and
      integrin alpha IIb beta 3. Integrin alpha IIb beta 3 is a remarkable receptor
      that not only stabilizes platelet-vessel wall and platelet-platelet adhesion
      contacts, but also transduces signals necessary for a range of other functional
      responses. These signals are linked to cytoskeletal reorganization and platelet
      spreading, membrane vesiculation and fibrin clot formation, and tension
      development on a fibrin clot leading to clot retraction. This diverse functional
      role of integrin alpha IIb beta 3 is reflected by its ability to induce the
      activation of a broad range of signaling enzymes that are involved in membrane
      phospholipid metabolism, protein phosphorylation, calcium mobilization and
      activation of small GTPases. An important calcium-dependent signaling enzyme
      involved in integrin alpha IIb beta 3 outside-in signaling is the thiol protease,
      calpain. This enzyme proteolyses a number of key structural and signaling
      proteins involved in cytoskeletal remodeling and platelet activation. These
      proteolytic events appear to play a potentially important role in modulating the
      adhesive and signaling function of integrin alpha IIb beta 3.

PMID- 10938899
TI  - The mitosis of fibroblasts in cell culture is enhanced by binding GP IIb-IIIa of
      activated platelets on fibrinogen.
AB  - A fibroblast cell culture model enables us to measure the mitogenic ability
      mediated by growth factors released from stimulated platelets under different
      conditions. Simultaneously the growth factors secreted in the culture medium were
      determined. Cell mitotic rate was measured by incorporation of 3H-thymidine on
      days 3, 5 and 7 of culture. PDGF, TGF-beta, EGF and IGF-I were determined by
      Western blot. When fibroblasts were grown on surfaces precoated with a mixture of
      fibrinogen and thrombin-stimulated platelets, the 3H-thymidine uptake (196,645 +/
      56,864 cpm/ml) was increased, in comparison to fibroblasts grown on uncoated
      surfaces, in medium supplemented with FBS (28,855 +/- 7329 cpm/ml). Neither
      thrombin-stimulated platelets without fibrinogen nor fibrinogen alone had
      positive effects on the mitogenic activity of fibroblast. Growth factors were
      identified only in a culture medium in which the cells were grown on surfaces
      precoated with fibrinogen and thrombin-stimulated platelets. Blocking the
      platelet integrin GP IIb-IIIa inhibited the release of growth factors from
      thrombin-stimulated platelets and consecutively the stimulation of mitosis by
      fibrinogen and activated platelets was absent. Antibodies against the growth
      factors added to the medium suppressed the stimulation of cell mitosis. These
      results show that delivery of growth factors from platelets' secretory granules
      is dependent on binding of fibrinogen to GP IIb-IIIa.

PMID- 10938898
TI  - Attenuation of alkalizing effect of thrombin by S-nitrosoglutathione in human
      platelets.
AB  - S-Nitrosoglutathione and sodium nitroprusside, two activators of the soluble
      guanylate cyclase, inhibit the intracellular calcium rise evoked by thrombin at
      an early step of the activation cascade. A similar effect is obtained with
      prostaglandin E1, a drug that increases cAMP. We have found that in human
      platelets thrombin 0.1 IU/ml (approximately 1 nmol/l) produced a transient
      increase of [Ca2+]i. After a 10-min preincubation at 37 degrees C in 100 mumol/l
      S-nitrosoglutathione the peak value was reduced by 79 +/- 4% (mean and SEM,
      percentage of the parallel control). The [Ca2+]i peak was reduced by 66 +/- 4%
      after preincubation in 100 mumol/l sodium nitroprusside, and by 90 +/- 2% after
      preincubation in 10 mumol/l prostaglandin E1. Thrombin has a slow alkalizing
      effect. After a 10-min preincubation at 37 degrees C in 100 mumol/l S
      nitrosoglutathione the change in pHi produced by thrombin was reduced by 35 +/-
      5%, but only 12 +/- 4% after preincubation in 100 mumol/l sodium nitroprusside.
      The alkalizing effect of thrombin was also blunted by 10 mumol/l prostaglandin
      E1: the change of intracellular pH was decreased by 39 +/- 5%. As a conclusion,
      these drugs in addition to the reduction of rise in [Ca2+]i have an inhibitory
      effect on the alkalizing response induced by thrombin.

PMID- 10938900
TI  - Two pathways for store-mediated calcium entry in human platelets.
AB  - In human platelets and other non-excitable cell types depletion of the
      intracellular calcium stores promotes calcium entry across the plasma membrane.
      Although the mechanism of this store-mediated calcium entry remains uncertain, it
      has been suggested that a tyrosine phosphorylation step could be involved. In
      support of this hypothesis various tyrosine kinase inhibitors have been shown to
      reduce store-mediated calcium entry in platelets, although this inhibition is
      never complete. Here we investigate the properties of store-mediated calcium
      entry in human platelets during the time course of its activation. Our data
      suggest that at least two pathways may contribute to store-mediated calcium entry
      in these cells. An early component, activated soon after the initiation of Ca2+
      store depletion, is insensitive to trivalent cations, SKF 96365 and tyrosine
      kinase inhibitors. This is followed by a second component which is inhibited by
      La3+, SKF 96365 and by tyrosine kinase inhibitors. These results suggest a role
      for tyrosine kinases in generating only the later stages of store-mediated
      calcium entry in platelets and may explain the incomplete inhibition of this
      pathway by inhibitors of tyrosine kinases.

PMID- 10938901
TI  - Platelet arachidonate cascade of migraineurs in the interictal phase.
AB  - Morphological and functional alterations of platelets in migraineurs may be
      linked to the development of migraine. We examined the eicosanoid synthesis of
      platelets of untreated female migraineurs in a headache-free period and compared
      it to that of age- and blood group-matched healthy female volunteers. In the
      platelets of headache-free migraineurs significantly less amounts of anti
      aggregatory prostaglandin D2 and prostacyclin, as well as of 12-L-hydroxy-5,8,10
      heptadecatrienoic acid (a potent endogenous inducer of endothelial prostacyclin
      production) were produced, while the synthesis of platelet aggregatory
      thromboxane did not differ when compared to that of healthy women. These results
      suggest that the platelet eicosanoids of migraineurs in the headache-free period
      might promote the development of cellular, vascular and neurological events
      inducing headache.

PMID- 10938902
TI  - Sphingosine-1-phosphate: characterization of its inhibition of platelet
      aggregation.
AB  - In this study, the ability of sphingosine-1-phosphate (S1P) to modulate platelet
      aggregation induced by other agents in platelet-rich plasma (PRP) was
      investigated. S1P alone did not stimulate platelet aggregation in PRP. S1P
      inhibited the platelet aggregation induced by the TRAP peptide (6.75 microM),
      noradrenaline (NA; 12.5 microM) and the Ca2+ ionophore (5.0-9.5 microM). S1P also
      increased the response time of platelets to arachidonic acid (AA), but decreased
      the response time to PMA. S1P displayed a dual effect on sodium fluoride (NaF)
      induced platelet aggregation and had no effect on the aggregation induced by ADP
      or lysophosphatidic acid (LPA). Furthermore, S1P blocked the synergistic
      interaction of oleyol-lysophosphatidic acid (O-LPA) with the TRAP peptide or
      noradrenaline, while the synergistic interaction of O-LPA with ADP remained
      largely unaffected.

PMID- 10938903
TI  - Effects of thrombin on intracellular calcium and pH in human and murine
      platelets.
AB  - The aim of this study was to compare the effect of thrombin (Thr) on cytosolic
      calcium [Ca2]+i and intracellular pH [pH]i in human and murine platelets. Rich
      platelet suspensions from both species were loaded with Fura-2 (2 microM) or
      BCECF (0.75 microM) by incubation with their respective acetoxymethyl esters to
      measure cytosolic calcium [Ca2+]i or intracellular pH [pH]i, respectively.
      Suspensions were challenged with increasing concentrations of Thr, from 0.1 to 10
      IU/ml. Basal [Ca2+]i in human platelets was 98 +/- 6 and 99.1 +/- 9 nM in rat
      platelets (n = 20). Thr increased [Ca2+]i, EC50 was 1.1 +/- 0.04 in human and
      0.97 +/- 0.06 IU/ml in rat platelets (n = 7). Extracellular Mg2+ (4 or 8 mM)
      abolished Thr response on [Ca2+]i. [pH]i in human was 7.09 +/- 0.08 and 7.11 +/-
      0.04 in rat platelets. Thr induced alkalinization of platelets in both species.
      Our results indicate that the potency of Thr to change [Ca2+]i and [pH]i was
      similar in both species, allowing for comparisons between human and murine
      platelets and to extrapolate results from an animal model to human pathology.

PMID- 10938904
TI  - Breast self-examination pamphlets: a content analysis grounded in fear appeal
      research.
AB  - In this study, we used the topic of breast self-examination (BSE) to illustrate
      how content analysis of promotional texts (already in existence, in the process
      of being created, or both) can provide supplementary data to that derived from
      audience analysis. Specifically, we used content analysis to isolate messages in
      BSE pamphlets that are consistent with the variables of severity, susceptibility,
      response efficacy, and self-efficacy, identified by existing fear appeal research
      and supported by other persuasion research as critical to the construction of
      effective health promotion messages. We then used statistical analyses to
      describe the relation among these 4 message variables. Our findings suggested
      that BSE pamphlets contain an unbalanced proportion of threat to efficacy
      arguments. Additionally, the efficacy messages were substantively weak. We
      contrasted these messages against the relatively strong mammography arguments
      contained in these pamphlets. We then provided recommendations for formulating
      stronger persuasive arguments in BSE promotional materials.

PMID- 10938905
TI  - Patients' perceptions of physicians communication and outcomes of the accrual to
      trial process.
AB  - The purpose of this study was to examine the relations among patients'
      perceptions of their physicians' communicative behavior during the informed
      consent interview, the patient's feeling of being confirmed by the physician and
      satisfied with care delivered by the physician, and the patient's decision to
      participate in a clinical trial or not. Respondents included 130 cancer patients
      who were eligible for a clinical trial and who had recently discussed trial
      participation with their physicians. Results indicated that a linear combination
      of the variables physician affiliative style, physician dominant or controlling
      style, patient satisfaction, patient confirmation, patient preference for
      decision making, patient desire for information, and patient age discriminate
      between patients who agree to participate in clinical trials and patients who
      refuse to participate. Physicians' affiliative communicative behaviors and
      patient satisfaction were clearly important to patients who agreed to
      participate. Motivations for patients who declined to participate in trials were
      less clear. Implications for physicians who offer clinical trials to their
      patients are that specific communication skills may enhance their patients'
      satisfaction and may help increase enrollment in clinical trials.

PMID- 10938906
TI  - Negotiating the tension between policy and reality: exploring nurses'
      communication about organizational wrongdoing.
AB  - This article explores the ways in which registered nurses communicate about
      organizational wrongdoing. Critical incidents were gathered from over 200
      registered nurses. Through the phenomenological process of description,
      reduction, and interpretation, 5 themes emerged as central to responses of policy
      violations and personal ethics in the workplace: (a) perceptions of wrongdoing,
      (b) upholding the ideals of the profession, (c) clarity and evidence of
      wrongdoing, (d) consequences of reporting, and (e) workplace dynamics. The
      interpretative findings focus on how these themes are united by a tension that
      nurses face in terms of adhering to policy while attempting to manage the
      realities of their everyday professional lives. A discussion of these findings,
      including how they relate to existing and future research and practice, is
      offered.

PMID- 10938908
TI  - The relation of communication to risk judgment and preventive behavior related to
      lead in tap water.
AB  - More and more communities are becoming concerned about health risks posed by lead
      and other health hazards in their drinking water. Our study, applying the model
      of innovation diffusion to the adoption of preventive health behaviors, found
      that reliance on health professionals for information about lead in tap water was
      associated with residents perceiving risk from this hazard, their sense of
      efficacy in dealing with it, and their adoption of preventive behaviors. Mass
      media and pamphlets mailed directly to residents were relatively ineffective.
      Results suggest that interpersonal channels may be the best way to reach
      individuals who live in areas of highest risk from tap water lead.

PMID- 10938907
TI  - Nurse versus family caregiver perspectives on hospitalized older patients: an
      exploratory study of agreement at admission and discharge.
AB  - Staff nurses and family caregivers of hospitalized elderly patients (> or = age
      70) play crucial roles in the health care and recovery of patients. This
      exploratory study identified and compared nurse and family caregiver perceptions
      about the patient's health condition, needs to stay healthy, and problems in self
      care at admission and discharge. Agreement between nurse and caregiver reports at
      both time points was assessed. Overall, findings confirmed a lack of agreement
      between nurses and family caregivers. At both time points, fewer nurses than
      caregivers focused on disease in describing the patients' health condition, and
      there was low agreement about diseases when mentioned. Although the great
      majority of nurses and caregivers reported one or more patient needs to stay
      healthy, and problems with self-care, there was little agreement about specific
      needs or problems mentioned at either time point. Findings may be attributed, in
      part, to current limitations on staff nurses' bedside time or insufficient
      opportunities, skills, or both to communicate with families about patients as
      part of comprehensive discharge planning. Organizational factors in large
      tertiary care hospitals may serve as a deterrent to nurse-family caregiver
      contact and communication during hospitalization.

PMID- 10938909
TI  - Transcending the technology of telemedicine: an analysis of telemedicine in North
      Carolina.
AB  - This study investigated the telemedicine program at East Carolina University
      School of Medicine. In-depth interviews, organizational texts, and archival
      records provided data for a case study that sought to understand what
      telemedicine is to organizational members and how they came to create this
      contextual reality. The goal of this study was to apply interpretive paradigmatic
      assumptions in the privileging of telemedicine as the very context of the
      organization. The findings explain how organizational members make sense of this
      new way of providing health care. Organizational members' talk revealed that
      telemedicine is multifaceted: It is access, an economic tool, education,
      technology, and a grant activity. With the single exception of technology, these
      themes emerged equally, regardless of whether the telemedicine provider was
      located at the urban hub site or the rural spoke site. Interestingly, members at
      both locations talked about critical events in relation to receipt of grant or
      financial support for new projects. Implications for future research are
      advanced.

PMID- 10938911
TI  - Customer service in dental offices: analyses of service orientations and waiting
      time in telephone interactions with a potential new customer.
AB  - Increasing competition among health care organizations has prompted greater
      concern for the quality of "customer service" in brief encounters with patients.
      This study examined service practices engaged by dental office staff interacting
      over the telephone with a potential new customer. The goals of the study were to
      determine whether the staff displayed customer-oriented and control-oriented
      service communication behaviors and to examine the relation between these service
      behaviors and waiting time required of customers. Structured observational data
      were collected in phone encounters with staff in 84 dental offices. Approximately
      40% of the staff engaged in the customer-oriented behavior of inviting the
      customer to share questions or concerns, and 31% exhibited the control-oriented
      behavior of reciting promotional pitches on behalf of the dental office. Six
      other communication behaviors were observed with less frequency. Staff who made
      customers wait on the line longer were more likely to use promotional pitches.
      Analyses revealed no significant relation between waiting time and other service
      communication behaviors.

PMID- 10938910
TI  - Adolescents' use of tobacco, health locus of control, and self-monitoring.
AB  - This study examined the association of the traits, health locus of control, and
      self-monitoring with adolescents' tobacco uptake. Participants were 112 rural
      adolescents (12 to 19 years old, M = 15.3). Of that sample, 33% used tobacco.
      Tobacco users were found to score lower on the dimension of Internality and
      higher on the dimension of Chance, as compared with nonusers of tobacco,
      indicating a more external Health Locus of Control. In addition, tobacco users
      were lower self-monitors than were nonusers. These results suggest that
      adolescents who use tobacco feel less in control of their lives in relation to
      nonusers, believe that chance plays a larger role in their health, and believe
      they may be unable to monitor and adapt their communication to achieve positive
      outcomes.

PMID- 10938912
TI  - Consumers as educators: implementation of patient feedback in general practice
      training.
AB  - There is growing interest in the adoption of patient-based assessments for the
      training of general practitioners. Consumers are in a unique position to comment
      on the quality of the doctor-patient interaction. Involving consumers as partners
      with general practice (GP) registrars and GP educators in the development of a
      patient feedback instrument enhances the relevance and acceptability of consumers
      as educators in GP training. It also demonstrates that social and medical agendas
      can be harmonized. Two patient feedback instruments on interpersonal skills were
      trialed in a training program for general practitioners in Australia. It was
      found that one of the instruments was more discriminating than the other because
      of its different response scale.

PMID- 10938913
TI  - Factors predicting safe-sex talk and condom use in early sexual relationships.
AB  - This study explored some of the antecedents and consequences of young adults'
      beliefs about safe-sex communication in their early couple relationships. The
      sample consisted of 237 unmarried, heterosexual Australian university students,
      16 to 19 years of age, approximately evenly divided between virgins and those
      with sexual experience. Drawing on a model of couple sexual communication as the
      product of prior experiences with communication, assertion, and conflict
      resolution in the family of origin, we examined links between these variables and
      respondents' attitudes and practices of safe-sex discussion and condom use with
      their dating partners. The results showed that women and nonvirgin men had more
      positive attitudes toward safe-sex communication than male virgins had.
      Difficulties with self-assertion outside of the sexual context and mothers' and
      fathers' use of avoidance as a conflict resolution strategy were negatively
      correlated with willingness to discuss safe sex, whereas mothers' more frequent
      safe-sex education was a positive predictor. The results of a hierarchical
      multiple regression analysis indicated that assertion, paternal conflict
      avoidance, and male gender were independent predictors of reluctance to negotiate
      for safer sex. At a behavioral level, positive attitudes to safe-sex discussion
      predicted having talked about AIDS and condoms with a dating partner as well as
      actual condom use by the subsample of daters who had experienced sexual
      intercourse. Implications for improving family and couple communication and for
      sex education were considered.

PMID- 10938914
TI  - Closing the knowledge-behavior gap in health promotion: the mediating role of
      self-efficacy.
AB  - Three cross-sectional data waves spanning 10 years (N = 2,055; 2,026; and 2,068)
      and 2 longitudinal data waves spanning 4 years (N = 1,384 and 1,151) from the
      Stanford Five-City Project (see Farquhar, Fortmann, Maccoby, & Haskell, 1985, for
      a full description of the project) were analyzed to determine whether diet self
      efficacy mediated the relation between diet knowledge and behavior. In the cross
      sectional data waves, knowledge-behavior correlations were greater among those
      with high (compared to low) self-efficacy. In the longitudinal data waves,
      knowledge-behavior correlations increased among those who increased their self
      efficacy and decreased among those who decreased their self-efficacy.
      Recommendations are made for public health campaigns designed to improve
      individuals' health behaviors.

PMID- 10938915
TI  - Limiting factors on the transformative powers of e-mail in patient-physician
      relationships: a critical analysis.
AB  - In this article I analyze doctor-patient use of e-mail within the context of the
      evolving doctor-patient relationship and ongoing changes in the U.S. health care
      system. Evidence from the published literature on doctor-patient relationships
      and doctor-patient communication, empirical studies of uses of the Internet by
      doctors and patients, and commentaries about the Internet's role in health care
      are examined and discussed to reveal common, unsupported assumptions about the
      likely impact of e-mail on the doctor-patient relationship and also the value
      structure associated with current e-mail practices between doctors and patients.
      I argue that existing research does not adequately account for the technical,
      professional, and economic forces that are shaping doctor-patient use of e-mail.
      I conclude that physicians' preferences for technical, instrumental exchanges
      with patients will likely mitigate the positive influence that e-mail could have
      on the doctor-patient relationship, and doctor-patient communication is unlikely
      to improve as a result of their use of e-mail.

PMID- 10938916
TI  - Long-term effects of language intensity in preventive messages on planned family
      solar protection.
AB  - A series of sun safety messages containing highly intense language and deductive
      logical style achieved the most immediate compliance by parents, particularly
      when they intended to improve protection. Inductive messages were more successful
      when no intentions existed (D. B. Buller, Borland, & Burgoon, 1998; D. B. Buller
      et al., 2000). Interviewers recontacted 568 parents during the winter following
      message dissemination and assessed solar protection. A 2 (language intensity) x 2
      (logical style) x 3 (behavioral intention) x 2 (person) mixed-model analysis of
      variance showed that parents receiving high-intensity, deductive messages
      reported the most improved solar protection and improvement was greatest when
      parents intended to improve protection. Over the long term, high language
      intensity may reinforce decisions to take preventive action and does not appear
      to provoke psychological reactance or resistance to these highly directive
      messages.

PMID- 10938917
TI  - Caregivers' predispositions and perceived organizational expectations for the
      provision of social support to nursing home residents.
AB  - This article presents the results of an investigation of caregivers' provision of
      supportive communication to nursing home residents. Five primary conclusions are
      drawn from the data: (a) Caregivers value providing affective over instrumental
      support; (b) caregivers believe they place more importance on supportive
      communication than their organizations; (c) role conflict is emotionally
      exhausting, but does not affect caregivers' self-evaluations or perceptions of
      residents; (d) caregivers' depersonalization of patients is related to their
      desire to communicate instrumental support; and (e) caregivers feel more
      accomplished when they believe their organization values supportive communication
      with patients. The implications of these findings for social support, caregivers'
      burnout, and nursing homes are discussed.

PMID- 10938918
TI  - The ability of the AIDS quilt to motivate information seeking, personal
      discussion, and preventative behavior as a health communication intervention.
AB  - A Solomon 4-group-design-style field experiment examined the ability of the NAMES
      Project Foundation's AIDS Memorial Quilt (AIDS Quilt) to motivate information
      seeking, personal discussion, and behavioral outcomes among those who viewed it.
      Results indicate that the AIDS Quilt intervention explained significant
      differences in information-seeking motivations and information-seeking behavior.
      Information-seeking motivation positively predicted actual information-seeking
      behavior, which in turn predicted increased discussion and decreased risky
      behavior. Information-seeking motivation in itself did not predict discussion or
      behavior. The results suggest that campaigns designed primarily to increase
      information-seeking motivation can result in desired behavioral outcomes.

PMID- 10938919
TI  - Karl Landsteiner and medical science in Vienna around 1900. The significance of
      laboratory medicine for clinical medicine.

PMID- 10938920
TI  - Molecular basis of red cell protein antigen deficiencies.
AB  - Blood group antigens reside on cell surface molecules of wide structural and
      functional diversity. Although all are serologically detectable on red blood
      cells, most are also expressed in non erythroid tissues, but with a few
      exceptions their biological role on erythrocytes and tissues often remains
      elusive. Deficiencies of these molecules seen either in rare blood group "null"
      phenotypes and/or associated with red cell membrane disorders, offer the
      opportunity to clarify their role in the cell membrane and to correlate their
      molecular abnormalities with cell dysfunctions. This review will summarize some
      of the present knowledge on these defects and on gene targeting studies developed
      to analyze the function of these molecules in animal models.

PMID- 10938921
TI  - Molecular pathology of prion diseases.

PMID- 10938922
TI  - HLA 2000.

PMID- 10938923
TI  - New tools in assessing immune reconstitution after hematopoietic stem cell
      transplantation.
AB  - BACKGROUND AND OBJECTIVES: Immune functions are impaired after allogeneic stem
      cell transplantation for several months depending on the age of the recipient,
      initial pathology, degree of HLA and minor histocompatibility antigens
      mismatches, origin and manipulation of the graft (unmanipulated or T-cell
      depleted bone marrow transplantation, cord blood) and post-transplantation events
      (acute or chronic graft-versus-host disease, relapse and infectious
      complications). MATERIAL AND METHODS, RESULTS AND CONCLUSION: In addition to
      lymphocyte phenotyping and functional assays, new tools are now available to
      monitor specific aspects of the immune response in the follow-up of hematopoietic
      stem cell transplantation: reconstitution of T cell diversity (spectratyping or
      Immunoscope), thymic function (TREC or "T-cell receptor rearrangement excision
      DNA circles") and antigen-specific T cell responses (HLA tetramers).

PMID- 10938924
TI  - Molecular genetics in haemophilia A.
AB  - Efficient mutation screening methods have greatly facilitated the analysis of the
      factor VIII gene. The fast growing number of identified mutations has led to an
      increasing understanding of the genetics in haemophilia A. In combination with
      the recently generated molecular models of the factor VIII protein systematic
      studies of structural-functional relationships of the factor VIII protein have
      started. The knowledge of the causative gene defect has also become an important
      instrument in haemophilia care with respect to prediction of the patients'
      clinical course and safe genetic counselling of relatives.

PMID- 10938926
TI  - Maximizing blood component donations.

PMID- 10938925
TI  - The molecular basis of inherited thrombophilia.
AB  - Even though it has been known for centuries that inherited defects of blood
      coagulation cause lifelong bleeding disorders, the existence of the counterpart,
      inherited thrombotic disorders, has been appreciated for only a few decades.
      Inherited thrombophilia can be defined as a genetically determined tendency to
      venous thromboembolism which characteristically occurs at a young age with no
      apparent cause and tends to recur. This article reviews the prevalence,
      biochemical and molecular basis of inherited thrombophilia, describes the main
      clinical manifestations and provides general guidelines for treatment. It is
      restricted to the more frequent and well-established causes of thrombophilia:
      antithrombin, protein C and protein S deficiency; resistance to activated protein
      C caused by mutations in coagulation factor V; and the gain-of-function mutation
      of factor II (prothrombin). Other causes of inherited thrombophilia are much
      rarer, such as dysfibrinogenemia, or not firmly established, such as
      abnormalities of the fibrinolytic system (plasminogen, histidin-rich
      glycoprotein) and thrombomodulin.

PMID- 10938927
TI  - Therapeutic hemapheresis as of 2000.
AB  - The main task of therapeutic hemapheresis remains doing the right thing and doing
      the right thing right. If objective results have been slow to take hold it is in
      large part because several physicians have resisted continuous improvement since
      therapeutic apheresis was considered so efficient to boomerang preventing
      elimination of unnecessary procedures and treatments. The right thing to do is
      treating patients who may respond in a specific phase of their disease,
      frequently along with the right drugs. Doing right the right thing is to take
      advantage of the new technologies and, medical culture which have led apheresis
      to the recent complexity and efficacy. In the following pages we are trying to
      update the state-of-the-art and new trends which characterize therapeutic
      apheresis at the beginning of 2000.

PMID- 10938929
TI  - Hemopoetic reconstitution of mice with stem cells generated in vitro.

PMID- 10938928
TI  - DNA vaccines.
AB  - BACKGROUND AND OBJECTIVES: Humoral and cellular immune responses to protein
      antigens can be efficiently primed by nucleic acid or DNA vaccination. In DNA
      based vaccination, immunogenic proteins are expressed with correct
      posttranslational modification, conformation or oligomerization; this ensures the
      integrity of epitopes that stimulate neutralizing antibody (B cell) responses.
      DNA (or RNA) immunization is exceptionally potent in stimulating T cell responses
      because antigenic peptides are efficiently generated in (endogenous or exogenous)
      processing pathways (without interference by viral proteins) from intracellular
      or extracellular protein antigens expressed after transient in vivo transfection.
      Both features are difficult to achieve with recombinant subunit vaccines produced
      in eukaryotic or prokaryotic expression systems. The current state of vector
      designs, strategies for delivery of DNA vaccines, priming humoral and cellular
      immune responses by DNA vaccines, experimental strategies facilitated by DNA
      vaccines, unique advantages of DNA vaccination, experience of DNA vaccination in
      preclinical animal models and clinical trials, and potential risks of DNA
      vaccination are discussed. Excellent reviews on DNA-based vaccination have been
      published recently [1-3].

PMID- 10938930
TI  - Surrogate tests.

PMID- 10938933
TI  - Quantification of Rh antibodies and antigens.

PMID- 10938932
TI  - Transfusion medicine in the 3rd millennium.

PMID- 10938931
TI  - Old and new tests: where will it end?
AB  - Testing has improved the safety of the blood supply. We have excellent serologic
      tests in place now and are implementing nucleic acid based tests to identify
      asymptomatic carriers of viruses during the infectious part of the pre
      seroconversion (window) period. However, the blood supply was already quite safe
      after a variety of other mechanisms had been put into place besides testing to
      screen out individuals at risk of carrying the most important transfusion
      transmissible agents. An important safety factor is the use of volunteer, unpaid
      (unremunerated) blood donors. The best alternative to implementing yet more tests
      to reduce, but not eliminate, the minute residual risks of transfusion
      transmission of such agents as HIV, HBV and HCV is the application of microbial
      inactivation technology to blood and blood components. Such microbially
      inactivated, cellular blood components should not have the risk of transmitting
      infectious agents, but may have other, different risks, since nothing has yet
      been shown to be one hundred percent safe (i.e., risk free). The use of a test to
      detect carriers of spongiform encephalopathies to prevent their theoretical
      transmission by transfusion may cause harm to donors and might increase risk for
      recipients by decreasing the available blood supply.

PMID- 10938934
TI  - Monoclonal antibodies to Rh D--development and uses.
AB  - Monoclonal anti-D has proved impossible to make in rodent systems. Human
      monoclonal anti-D has been produced using EBV transformed peripheral B cells,
      coupled with fusions to myeloma cell lines. More recently molecular biology
      techniques have been used to produce monoclonal anti-D. The range of monoclonal
      anti-D produced is considered. The selection of monoclonal anti-D for use as
      blood grouping reagents for typing donors and recipients is reviewed--all types
      of D positive should be typed as positive when donors are considered. However,
      DVI patients should be typed as D negative. Considerations for the development of
      monoclonal anti-D for prophylactic use are reviewed.

PMID- 10938935
TI  - Site directed mutagenesis of the human Rh D antigen: molecular basis of D
      epitopes.
AB  - Previous attempts to define the molecular configuration of D epitopes has been
      confined to the analysis of the serological profile and Rh D molecular structure
      of partial D phenotypes. There are numerous drawbacks in this approach, most
      fundamental of which is that with the exception of RoHar, partial D phenotypes
      are defined by the loss of D epitope expression, and is thus difficult to
      directly correlate a specific amino acid to a particular D epitope. Furthermore,
      most partial D phenotypes are associated with multiple amino acid changes in the
      mutant Rh protein species associated with partial D expression. In our study we
      have applied site directed mutagenesis to introduce RhD amino acids in a stepwise
      manner to a Rh cE cDNA. This cDNA was introduced into K562 cells using retroviral
      mediated gene delivery, and D epitope expression analysed by flow cytometry. Our
      study provides evidence for at least six different epitope clusters on the
      external face of the Rh D protein. The relative predicted positions of these
      epitope clusters has resulted in us presenting a model for the hypothetical
      arrangement of external Rh D protein loops.

PMID- 10938936
TI  - Molecular genetics of ABO.
AB  - This year commemorates the 100th anniversary of the discovery of the ABO blood
      group system by Karl Landsteiner. His findings of red cell agglutination by serum
      and recognition of blood groups laid the scientific basis for safe practice of
      blood transfusion. Even though dozens of blood systems have been identified, the
      ABO system still remains to be one of the most important systems in transfusion
      medicine. In 1990, we elucidated the molecular genetic basis of three major
      alleles at the ABO locus. Since then we have witnessed the progress in our
      understanding of ABO genes and A and B glycosyltransferases specified by a
      variety of functional alleles at this locus. Mutations affecting the activity and
      specificity of the enzymes have been identified. Not only has ABO genotyping
      become possible, but it has also become possible to genetically engineer the
      activity and specificity of the enzymes. We are now at a point of embarking upon
      the quest of understanding the functional significance of ABO polymorphism.

PMID- 10938937
TI  - Molecular genetics of H.
AB  - BACKGROUND AND OBJECTIVES: Formal genetics of ABO, H-h and Se-se systems
      illustrate that these three systems are genetically independent MATERIALS AND
      METHODS: Population analysis of phenotypes and family segregation of the ABH
      related genetic markers RESULTS: Inactivating mutations of FUT1 and FUT2 are
      compatible with a structural gene model assuming that FUT1 and FUT2 genes encode
      for two distinct enzymes, one encoding for the H antigen expressed in red cells
      (FUT1) and the other encoding for the H gene expressed in saliva (FUT2)
      CONCLUSION: Most inactivating mutations of FUT1 and FUT2 genes are located in the
      coding region of the genes and are nonprevalent sporadic mutations of relative
      recent appearance.

PMID- 10938938
TI  - Molecular genetics of RH.
AB  - BACKGROUND AND OBJECTIVES: The two Rhesus proteins, RhD and RhCE, constitute one
      of the clinically most relevant blood group antigen system. In the last two
      years, the understanding of RH molecular genetics has increased considerably. The
      state of the current knowledge was briefly summarised. MATERIALS AND METHODS:
      Recent reviews, original work since 1999 and own results were utilised. RESULTS:
      The structure of the RH gene locus comprising RHD, RHCE and SMP1 was presented.
      True RHD genotyping became feasible by establishing the molecular basis of the
      most prevalent RH haplotype in whites harbouring the RHD gene deletion and of the
      RHD pseudogene RHD psi in Africans. Molecular and serologic characteristics of
      weak D and partial D alleles were compared. Closely related alleles for both,
      weak D and partial D, were collated as examples contributing to the understanding
      of RH phylogeny. CONCLUSION: The RH gene locus is a model system for molecular
      polymorphism in clustered genes and suitable for studying molecular evolution in
      humans. It lends itself for developing molecular diagnostics because its genetics
      is appropriately complex and challenging; yet the expressed phenotypes have been
      studied for decades and are well understood. Legal and ethical issues that are
      rightfully of public concern would not be infringed if RH genotyping will be
      attempted on a massive scale.

PMID- 10938939
TI  - Epitopes on Rh proteins.
AB  - Analyses of the reactions of monoclonal anti-D with Rh D variant red cells have
      shown that there are at least 24 different epitopes of the Rh D antigen. Similar
      studies Of Rh E variant red cells with monoclonal anti-E indicate that there are
      at least 4 epitopes of the Rh E antigen. The relation of these serologically
      defined epitopes to the structure of the Rh proteins is reviewed. Most epitopes
      are discontinuous, with critical residues present in different loops of the
      proteins.

PMID- 10938940
TI  - Clinical impact of platelet glycoprotein polymorphism.

PMID- 10938941
TI  - Molecular genetics of granulocyte polymorphisms.
AB  - BACKGROUND AND OBJECTIVES: Granulocyte (neutrophil) antibodies have been
      implicated in transfusion-related acute lung injury (TRALI) and immune
      neutropenias. In the last decade enormous efforts have been made to characterize
      the involved alloantigens. MATERIALS AND METHODS: Review of the literature.
      RESULTS: The NA1, NA2, and SH antigens have been identified as polymorphic forms
      of the neutrophil Fc gamma receptor IIIb encoded by three alleles. The antigens
      MART and OND have been located on leucocyte adhesion molecules (beta 2 integrins)
      and were found to be due to single nucleotide mutations in the alpha M (CD11b)
      and alpha L (CD11a) subunits. Recently, we succeeded in throwing light on the
      primary structure of the NB1 antigen. On the basis of these findings a new
      nomenclature has been introduced for human neutrophil alloantigens (HNA
      nomenclature). Glycoprotein location has made the development of antigen-specific
      immunoassays possible and antigen characterization on the molecular level now
      allows genotyping by DNA techniques. CONCLUSION: Considerable progress has been
      made in the characterization of granulocyte antigens. Further studies will
      improve our diagnostic tools and will facilitate the prevention and management of
      transfusion reactions and immune neutropenias.

PMID- 10938942
TI  - Flow cytometry: the standard for monitoring the onset of apheresis and for the
      evaluation of stem and progenitor cell graft quality.
AB  - Several high-quality protocols exist that describe the methodological and
      technical aspects of the flow cytometric analyses of stem and progenitor cells.
      In addition, recent advances in automation and quantitative analyses show
      promising results. For further improvement of the test quality and more objective
      control, internal as well as external quality control is mandatory. In addition,
      cost aspects move into the focus of interest and have to be considered.
      Alternative methods such as volumetric capillary cytometry or haematological
      analyzers are of limited use for stem and progenitor cell analyses. Currently,
      flow cytometry represents the gold standard for monitoring the onset of apheresis
      and to evaluate the quality of stem and progenitor cell grafts. In the near
      future, only in vitro diagnostics that are CE-labelled or FDA-approved should be
      used for these analyses.

PMID- 10938943
TI  - Flow cytometric analysis of platelets.
AB  - BACKGROUND AND OBJECTIVES: Despite recent progress in our understanding of
      platelet function in vitro, there remains a remarkable paucity of methods to
      study platelet function in vivo. MATERIALS AND METHODS: We have developed novel
      three color whole blood flow cytometric methods for tracking of infused platelets
      and measurement of their function in vivo. RESULTS: These methods were used to
      demonstrate that circulating P-selectin-positive (degranulated) platelets rapidly
      lose surface P-selectin to the plasma pool, but continue to circulate and
      function. CONCLUSIONS: 1) These studies strongly suggest that the measurement of
      platelet surface P-selectin in platelet concentrates stored in the blood bank
      should not be used as a predictor of platelet survival or function in vivo. 2)
      The described methods provide the means to answer many previously difficult to
      address questions about in vivo platelet function in transfusion medicine.

PMID- 10938944
TI  - Stealth erythrocytes--a possible transfusion product for the new century?

PMID- 10938945
TI  - Expression of red cell surface antigens during erythropoiesis.
AB  - BACKGROUND AND OBJECTIVES: We have analysed the appearance and disappearance of
      cell surface markers during erythropoiesis, in vitro. MATERIALS AND METHODS:
      CD34+ haemopoietic progenitor cells were isolated from umbilical cord blood and
      cultured by three different methods, all in the presence of erythropoietin. The
      methods included two one-stage techniques, one serum-free, the other with serum
      present, and one serum-present two-stage method. RESULTS: The appearance of cell
      surface markers on the differentiating erythroid cells varied slightly from
      sample to sample, but differed more substantially between techniques, with the
      cells differentiating more rapidly in the culture media containing serum. The
      order of appearance of the markers, which was constant in the three methods, was
      as follows: glycophorin C, Kell, Rh-associated glycoprotein, glycophorin A, band
      3, Rh proteins, and glycophorin B. CONCLUSION: Cell surface antigens can be used
      as markers for mapping the progress of erythroid differentiation during
      erythropoiesis.

PMID- 10938946
TI  - Prenatal determination of fetal blood group status.
AB  - BACKGROUND AND OBJECTIVES: The prenatal determination of fetal blood group status
      by molecular techniques has been used in the clinical management of alloimmunised
      pregnancies for seven years, in particular for the definition of fetal Rh D, c
      and E, K, Fya and Jka status. This has arisen in response to the definition of
      the molecular bases of human blood group polymorphism. MATERIALS AND METHODS: PCR
      based amplification assays have been designed to define fetal blood group status,
      where the source of template DNA is normally derived from amniotic fluid or
      chorionic villus. Recently, non-invasive methods have been explored to obtain
      fetal DNA from maternal peripheral blood. RESULTS: PCR-based tests are now
      available to screen for all fetal medicine significant blood group antigens. The
      Rh system is the most complex, and assays to define Rh genotype have been
      modified in response to our increased understanding of the molecular biology of
      this blood group system. CONCLUSION: Prenatal diagnosis of fetal blood group
      status is now in widespread use in the clinical management of HDN. Non-invasive
      testing, if applied in the clinical setting may invoke a dramatic increase in the
      numbers of pregnancies that may be analysed prenatally.

PMID- 10938947
TI  - Red cell transfusion strategies in the ICU. Transfusion Requirements in Critical
      Care Investigators and the Canadian Critical Care Trials Group.
AB  - Transfusion of red blood cells continues to be an important therapy for treatment
      of anemia in intensive care settings. The critically ill are a population
      predisposed to the adverse outcomes of anemia and, as such, the risks imposed on
      them by transfusion therapy is one of great interest. Over the past decade there
      has been a shift in transfusion practice with guidelines being developed that
      promote more conservative and safer use of blood. The Transfusion Requirements in
      Critical Care (TRICC) trial clearly established the safety of a restrictive
      transfusion strategy, suggesting that physicians could easily minimize exposure
      to allogeneic RBCs by lowering their transfusion threshold. Further research will
      add to the generalizability of this study as well as explore the possible
      mechanism to explain why red cell transfusions did not improve outcomes in the
      critically ill.

PMID- 10938948
TI  - Trigger for platelet transfusion.
AB  - BACKGROUND AND OBJECTIVES: The terms 'platelet transfusion trigger' are used in
      the scientific literature to indicate a value of the platelet count above which
      prophylactic platelet transfusion is usually not indicated. Most clinicians share
      the currently prevalent consensus published in several guidelines that a platelet
      transfusion trigger of 10,000 platelets per microliter is safe in stable
      oncohematology recipients carefully monitored at both the clinical and laboratory
      levels, whereas higher values may be necessary in patients with high fever,
      infection, splenomegaly, rapid platelet count decrease, on drugs able to affect
      platelet function and survival, in cases undergoing invasive maneuvers and in
      some pediatric patients such as premature newborns. The safety of this policy is
      supported by the results obtained in several randomized clinical trials and
      prolonged observational studies. Lowering the platelet transfusion trigger from
      the traditional value set at 20,000 platelets per microliter to the currently
      recommended value of 10,000 per microliter further stresses the importance of
      high-quality, sufficient and prompt platelet availability and close cooperation
      between clinicians and blood transfusion specialists. Furthermore, it requires a
      clear understanding of the discriminatory power of current automated hematology
      counters at very low platelet counts. In the surgical setting, where randomized
      clinical trials on the most appropriate platelet transfusion trigger are largely
      missing, current guidelines propose to maintain higher platelet count values
      (50,000-100,000 per microliter) during surgery and in the early postoperative
      period.

PMID- 10938949
TI  - Platelet substitutes.
AB  - Many experimental approaches have been explored to produce hemostatically active
      novel human platelet products and substitutes capable of long-term storage. These
      include: platelet storage in the frozen state; storage in the cold (4 degrees C)
      in the liquid state; photochemical methods for the inactivation of viruses,
      bacteria and protozoa; infusible platelet membranes; and rehydrated lyophilized
      platelets. In addition to products using human platelets as their primary
      manufacturing source, other approaches have been used to make non-platelet
      derived substitutes that might be capable of in vivo hemostasis. These include
      production of red blood cells, or liposomes, bearing hemostatically active agents
      on their surfaces; and fibrinogen-coated albumin microcapsules or microspheres.
      The development of platelet substitutes is an increasing scientific and
      technological endeavor and there are many reasons to believe that platelet
      substitutes will become more efficacious and safer to use over time. Ultimately,
      such work will result in safe and effective platelet substitutes being available
      for clinical use in thrombocytopenic or other patients with increased risk for
      bleeding.

PMID- 10938950
TI  - Antibodies to factor VIII in hemophilia A patients.
AB  - Inhibitor development represents the main complication in the treatment of
      haemophilia A. The risk of inhibitor formation is in part genetically determined
      by the type of the underlying factor VIII gene lesion but environmental factors
      may also play an important role. Due to the lack of efficiency of factor VIII in
      these patients other therapeutic agents must be used for the treatment of
      bleedings, however, none is as effective as factor VIII in a non-inhibitor
      patient. Therefore, the eridication of the inhibitor through immune tolerance
      therapy is the treatment of choice. Centralized national and international immune
      tolerance registries have collected the results and show cost effectiveness of
      this treatment.

PMID- 10938951
TI  - Clinical use of intravenous immunoglobulins.
AB  - Prophylaxis and treatment with i.v. immunoglobulins must envisage preparations
      from normal or hyperimmunised human donors, animals (horses and rabbits) as well
      as monoclonal and genetically and proteomically engineered chimeric or
      recombinant antibodies. The latter group of antibody sources from the bioreactor
      source must be seen in the context of traditional antibody therapy, including
      passive immunization, general antibody substitution and provision of lost immune
      regulatory capacities such as downregulation of complement activation,
      attenuation of Fc receptor apparatus as well as anti-idiotypic potential. Beyond
      summarizing the present evidence based indications the present review is an
      outlook at the doorstep for future possibilities to improve precision of antibody
      dependent treatments and avoiding side effects which formerly compromised
      widespread use.

PMID- 10938952
TI  - Extracorporeal photochemotherapy--present and future.
AB  - Extracorporeal photochemotherapy (ECP) was introduced by Edelson and co-workers
      in 1985. Since then the therapy, though still controversial in specific
      indications, has received wide acceptance and is presently been used in over 160
      centers in Europe and the U.S.A. for a number of important dermatological and non
      dermatological indications. Convincing data in the past few years has documented
      that ECP is associated with a very low side-effect profile. As of 2000 ECP
      continues to be used in the treatment of cutaneous T-cell lymphoma, alone or in
      combination with other treatment modalities, and increasingly in the management
      of additional T-cell mediated diseases, acute as well as chronic Graft versus
      Host Disease (GvHD) after allogeneic bone marrow transplantation in particular.
      ECP has also been shown to play an important role in the treatment of acute as
      well as chronic allograft rejection, in renal, lung, and cardiac transplant
      recipients and lately steroid refractory inflammatory bowel disease. A number of
      mechanisms for its efficacy have been proposed whereby at present induction of
      anticlonotypic immunity directed against pathogenic clones of T lymphocytes may
      be an important concept. Treatment related apoptotic death of involved T cells
      and concurrent activation of antigen presenting cells may also closely relate to
      mechanisms associated with this therapy.

PMID- 10938953
TI  - Progress in improving the pathogen safety of red cell concentrates.
AB  - Current methods of preparing red cell concentrates do not include a process step
      to decontaminate pathogens potentially present in the transfusion product.
      Although substantial progress has been made in the reduction of the frequency of
      transmission of HIV, HCV, HBV and HTLV-I as a result of the implementation of
      diagnostic screening processes, the need for further reduction in transmission
      rate of these viruses remains. In addition, there are viruses which are known to
      be be present in blood but for which no screening test has been implemented to
      remove contaminated units from the blood supply. These viruses include but are
      not limited to TTV, HGV and Parvo B19. Finally, the lack of a pathogen
      inactivation process for red cells maintains the blood supply in a state of
      vulnerability to new viruses or virus variants as they enter the donor
      population. Recently, substantial progress has been made in the research and
      development of a class of chemical compounds designated as INACTINE. These
      compounds are being investigated for their potential to inactivate viruses in red
      cells without adversely affecting their physiologic function. One of the INACTINE
      compounds, designated as PEN110, is now in the clinical trial phase of
      development.

PMID- 10938954
TI  - Inactivation of viruses, bacteria, protozoa and leukocytes in platelet and red
      cell concentrates.
AB  - Substantial increments in the safety of blood transfusion have been achieved
      through continued improvements in donor testing, yet residual concern about the
      safety of blood components persists. To further reduce the risk of transfusion
      associated infection, additional measures, such as nucleic acid testing for
      selected pathogens, are being introduced. Transfusion of cellular components has
      been implicated in transmission of viral, bacterial, and protozoan diseases [1].
      While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus
      (HCV), cytomegalovirus (CMV), and the retroviruses, such as human
      immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV) can be
      transmitted through cellular components, other pathogens are emerging as
      potentially significant transfusion-associated infectious agents. For example,
      transmission of protozoan infections due to trypanosomes [2-4] and babesia have
      been reported [5]. In addition to viral and protozoal infectious agents,
      bacterial contamination of platelet and red cell concentrates continues to be
      reported [6, 7]; and may be an under reported transfusion complication [8]. More
      importantly, new infectious agents may periodically enter the donor population
      before they can be definitively identified and tested for to maintain consistent
      safety of the blood supply. The paradigm for this possibility is the HIV
      pandemic, which erupted in 1979. During the past decade a number of methods to
      inactivate infectious pathogens have been developed and have entered the advanced
      clinical trial phase.

PMID- 10938955
TI  - The use of riboflavin for the inactivation of pathogens in blood products.
AB  - BACKGROUND AND OBJECTIVES: In recent years, the desire to develop methods to
      inactivate pathogens in blood components has continued to grow. Several of these
      proposed approaches have been introduced or are currently in clinical studies.
      The use of chemical inactivating agents must be considered in terms of the
      current safety of the blood supply and the potential risks that the introduction
      of new chemical entities into blood components may carry. The impact which these
      treatment procedures have on the in vitro and in vivo performance of these
      products must also be considered relative to the potential benefit of the
      pathogen inactivation potential they offer. This paper will discuss one possible
      approach for inactivating pathogens in blood using vitamin B2, Riboflavin, and
      light. MATERIALS AND METHODS: We have used Riboflavin for treating plasma and
      platelets and evaluated protein quality and platelet function in vitro. Initial
      toxicology tests to assess the impact of infusion of photoproducts generated in
      these processes have also been conducted in rodents. Cytotoxicity evaluations
      have been used to assess the possible impact of photoproduct toxicity in vivo.
      Virus and bacteria spiking studies using a variety of human and animal model
      pathogens have been conducted in order to asses the efficacy of this process.
      RESULTS: Initial toxicology assessment of the photoproducts of Riboflavin
      generated under the proposed treatment conditions have been favorable. Virus and
      bacteria clearance studies have demonstrated efficacy of the procedure against a
      wide range of human and animal pathogens, including intracellular HIV-1. Studies
      with platelet and plasma function indicated reductions in vitro comparable to
      other proposed treatment approaches. CONCLUSION: The use of Riboflavin in a
      photochemical decontamination process for blood components shows promise.

PMID- 10938957
TI  - Leukocyte counting during process control of leukoreduced blood components.
AB  - BACKGROUND AND OBJECTIVES: To describe the characteristics of counting assays
      used for process control of leukoreduction. MATERIALS AND METHODS: Literature
      review. RESULTS: Counting assays with good performance characteristics are an
      essential element of the process control of leukoreduction. A recent multicenter
      study by a Working Party of the ISBT has evaluated three widely used methods for
      counting low numbers of leukocytes in leukoreduced blood. CONCLUSION: Automated
      methods provide greater accuracy and better inter-laboratory precision than
      Nageotte hematocytometry. However, deterioration of performance as a result of
      prolonged sample shipment remains an obstacle to centralized testing services.
      Although several mathematical approaches have been used to model the distribution
      of residual leukocytes in leukoreduced blood, no single model has been shown to
      be clearly superior.

PMID- 10938956
TI  - New developments in plasma fractionation and virus inactivation.
AB  - Ethanol fractionation has been used for fifty years to prepare therapeutic
      proteins from human plasma. Although the method has been very successful, there
      are now newer techniques available, which might at least in part replace ethanol
      fractionation. Whether or not this will occur depends on the economic benefits
      the new methods offer. Although transmission of viruses through blood products is
      nowadays fortunately a rare event, the search for alternative inactivation and/or
      removal methods for viruses continues. The small, non-enveloped viruses are
      particularly difficult to deal with, and any new method should address this
      problem with a high priority. Transmission of spongiform encephalopathies
      (Creutzfeld-Jakob and similar diseases) by blood and blood products has not been
      observed so far. Preliminary experimental evidence indicates that the putative
      causative agent(s) are removed from the final products during fractionation.

PMID- 10938958
TI  - Clinical significance of leukoreduktion of blood components.
AB  - The clinical significance of leukocyte reduction of all blood components must be
      deducted from patients transfused in the surgical setting. Under these
      circumstances many factors contribute to morbidity and mortality, while such
      factors can be candidates for confounders. Moreover, to investigate effects on
      infrequent events such as post-operative mortality and multiple organ dysfunction
      syndrome, large patient cohorts must be studied. Our studies suggest that
      leukocytes or leukocyte aggregates in red cell transfusions indeed may be harmful
      if larger dosages are administered under certain clinical circumstances. A
      critical leukocyte load seems to start with approximately 2.5 x 10(9). Reducing
      the leukocyte contamination of red cell components, not necessarily by
      filtration, may benefit patients who require multiple transfusions within a short
      time interval.

PMID- 10938960
TI  - Transmission of parasites and bacteria by blood components.
AB  - BACKGROUND AND OBJECTIVES: Although most attention has been paid to viral
      infections as a complication of transfusion, some parasitic infections are
      readily transmissible and generate a heavy burden of disease, particularly in the
      developing world. Additionally, bacterial infection as a result of transfusion is
      the most frequent serious outcome of transfusion in the developed world.
      MATERIALS AND METHODS: Review of current literature and ongoing research studies.
      RESULTS: Malaria and Chagas' disease continue to be a serious problem in endemic
      areas, but are also of concern as a result of their introduction into other
      regions. Means to control or detect bacterial contamination, particularly of
      platelet concentrates, are needed, but no simple, effective approach is
      available. CONCLUSION: Continued development and implementation of tests and of
      inactivation procedures will result in the eventual control of transfusion
      transmitted parasitic and bacterial disease.

PMID- 10938959
TI  - Prions and transfusion medicine.
AB  - BACKGROUND AND OBJECTIVES: There is growing concern at national and international
      levels that blood supplies might be contaminated with Creutzfeldt-Jakob disease
      (CJD) agents (prions). MATERIALS AND METHODS: This review on CJD and blood
      focuses on experimental and epidemiological data, available tests, factors
      contributed by donors and recipients, and production processes. All of this has
      been recently detailed in excellent reports and opinions which are summarised
      here. RESULTS: Solid evidence from experimentally infected animals, and
      fragmentary evidence from naturally infected humans, indicates that blood may
      contain low levels of the infectious agent, yet blood products have never been
      identified as a cause of CJD in humans. CONCLUSION: The evaluation of all
      relevant data leads to the opinion that transmission of CJD by blood and blood
      products either does not occur or does not contribute to the CJD epidemiology.
      Although a hazard cannot be excluded, a real risk is not recognisable. As the
      experience with variant CJD (vCJD) is limited, the same statement cannot be made
      for vCJD [1]. In consequence, it is mainly the risk of vCJD that might have
      relevance for transfusion medicine; this has already resulted in some
      precautionary donor exclusion regulations.

PMID- 10938961
TI  - Emerging viruses in blood transfusion.
AB  - BACKGROUND AND OBJECTIVES: The development of new technologies leads to the
      discovery of new viruses. For each of these new infectious agents relevance to
      transfusion needs to be assessed. MATERIALS AND METHODS: The questions to be
      answered are transmissibility by transfusion, pathogenicity, prevalence in blood
      donors, persistence and the availability of screening assays. RESULTS: Since
      1995, four new viruses have been identified and for three of them extensive
      studies have been carried out. GBV-C/HGV and TTV were both initially thought to
      be related to post-transfusion hepatitis but neither were proven to be in any way
      related to hepatitis and are still in search of a disease. HHV-8 is a major
      factor in the pathogenesis of Kaposi's sarcoma and other tumours related to
      immunodeficiency. HHV-8 transmission by organ transplantation but not by
      transfusion has been demonstrated. SEN-V has been claimed as a potential cause of
      non-A-E hepatitis but no data has been published. CONCLUSION: To date, none of
      the emerging viruses have been proven relevant to transfusion.

PMID- 10938962
TI  - Hepatitis C lookback in Canada.
AB  - BACKGROUND AND OBJECTIVES: Since March 1990, all blood donations in Canada are
      screened by enzyme-linked immunosorbent assay (EIA) for antibodies to HCV, with
      confirmatory testing done using a recombinant immunoblot assay (RIBA). Because
      HCV may cause chronic asymptomatic hepatitis, in 1995, the Canadian Red Cross
      began targeted HCV lookback studies on all confirmed positive donations. These
      have been continued by the two new operators of the blood system in Canada, Hema
      Quebec and the Canadian Blood Services. Subsequent to recommendations made in the
      public inquiry into the Canadian blood system, led by judge Krever, general
      lookback through letter notification of all patients transfused in the years
      prior to the introduction of anti-HCV testing was initiated in several pediatric
      hospitals, and later in several Canadian provinces. MATERIALS AND METHODS:
      Targeted HCV lookback was done for all donors confirmed positive by RIBA testing
      from the start of HCV testing in 1990. In 1999, stored RIBA 2 indeterminate
      samples were re-tested by RIBA 3, and lookback performed on confirmed positive
      donations. In the province of Quebec, hospitals were surveyed to determine
      methods and resources involved in lookback. Provinces performing general letter
      notification entered hospital transfusion records into a central transfusion data
      bank, and performed linkage with other provincial data banks to remove deceased
      patients and obtain current addresses. RESULTS: As of January 2000, targeted
      lookback had been completed on 4,859 components of 1,628 anti-HCV positive repeat
      donors. 2,991 recipients were deceased, and 451 were not found or tested. Of the
      1,422 recipients tested, 954 (67%) were anti-HCV positive. Approximately half
      were already aware of their HCV status. Lookback efforts in hospitals were
      hampered by lack of resources and manual records. General letter notification in
      British Columbia (BC) and Prince Edward Island (PEI) led to the testing of 38,960
      and 1,953 recipients respectively, with 5.0 and 2.2% of tested recipients found
      to be anti-HCV positive. CONCLUSION: In completed targeted lookback
      investigations, 19% of components are eventually linked to an anti-HCV positive
      recipient. These results are very similar to those obtained in other countries,
      such as Denmark and the UK. In general letter notification lookbacks, the
      frequency of anti-HCV in the tested recipients is approximately twice the
      frequency of the general population.

PMID- 10938963
TI  - HIV, HBV and HCV: new developments related to transfusion safety.

PMID- 10938964
TI  - NAT and viral safety in blood transfusion.
AB  - BACKGROUND AND OBJECTIVES: Nucleic acid testing was introduced at our blood
      transfusion service in order to reduce the diagnostic preseroconversion window
      for transfusion relevant viruses. MATERIALS AND METHODS: Up to 96 donor samples
      were pooled overnight by two Tecan Genesis RSP 150 pipettors. Pools were
      centrifuged at 48,000 g for one hour to enrich viruses. Viral nucleic acids were
      extracted from centrifugation pellets using modified Qiagen viral RNA kit. HIV
      and HBV sequences were amplified by in house TaqMan PCR's with patented primers
      and probes for HBV. HCV PCR was performed by Roche Amplicor V2.0. "Nadis"
      software was developed for pooling, resolving positive pools and data
      communication with main frame computer. RESULTS: PCR testing was introduced in
      January 1997 for HCV HBV and HIV-1 for all plasma products and for labile
      components at the 21st of April 1997. Throughput increased from 2000 to 4000
      samples per day. PCR testing is done in parallel to serological testing and
      products are released eight hours after pooling is completed. Until January 2000,
      1,078,940 donations have been tested in 13,274 pools. A total of seven PCR only
      positives were identified (3 HCV, 3 HBV, 1 HIV). CONCLUSION: The yield of PCR
      testing for transfusion relevant viruses confirms theoretical estimates on the
      residual risk of antibody screening.

PMID- 10938965
TI  - Molecular genetics of HLA.
AB  - A review of the molecular genetics of the HLA gene complex from a tissue typer's
      point of view.

PMID- 10938966
TI  - MHC: function and implication on vaccine development.
AB  - The purpose of this State of the Art review is to present an overview of
      structural and functional aspects of human MHC molecules and how polymorphisms in
      HLA molecules determine the nature of the antigenic peptides bound and how such
      may impact upon rational vaccine development. The following areas will be
      discussed: elements of immune recognition, class I and class II structure and
      function, the class I antigen processing pathway, class II antigen processing and
      presentation, functional divergence among T-cells recognizing class I or class II
      MHC molecules, and rational vaccine development. While the first section will
      review our current understanding of MHC structure and function, the latter part
      will draw on my own work with Hepatitis C Virus (HCV) antigens.

PMID- 10938967
TI  - Impact of HLA matching on hematopoietic cell transplants from unrelated donors.

PMID- 10938968
TI  - Immunomodulation by blood transfusions.
AB  - Blood transfusions can affect the immune response in two opposite ways. They may
      either lead to immunization or to tolerance induction. Immunization is reflected
      by the induction of HLA alloantibodies and T cell activation while the induction
      of tolerance is suggested by the enhanced graft survival in transfused versus non
      transfused recipients. The immunological mechanism leading to downregulation of
      the alloimmune response is not clear. One possible explanation is the induction
      of a Th2 response by non-professional antigen presentation by the transfused
      blood cells. On the other hand, evidence is accumulating that the degree of HLA
      compatibility between transfusion donor and patient is a determining factor.
      Transfusions sharing at least one HLA-DR antigen with the recipient induce
      tolerance while fully HLA-DR mismatched transfusions lead to immunization. The
      importance of the degree of HLA-DR sharing suggests a central role for CD4+
      regulatory T cells. We hypothesize that indirect recognition of an allopeptide in
      the context of self-HLA-DR on the transfusion donor by CD4+ T cells of the
      recipient might be the clue to tolerance induction. Preliminary data show indeed
      that CD4+ T cells specific for an allopeptide in the context of self HLA-DR are
      able to downregulate the alloimmune response of autologous T cells. Further
      analysis of transplanted patients, who have received an HLA-DR shared
      transfusion, should reveal whether such CD4+ regulatory T cells are indeed
      responsible for the beneficial effect of pretransplant blood transfusions.

PMID- 10938969
TI  - Treatment of post transfusion graft-versus-host disease.
AB  - BACKGROUND AND OBJECTIVES: In Japan, so many cases of post-transfusion graft
      versus-host disease (PT-GVHD) have been reported, and no effective treatment has
      been reported. MATERIALS AND METHODS:  RESULTS: Totally 61 cases of PT-GVHD have
      been collected, and their background were analyzed. A serine protease inhibitor,
      nafamostat mesilate(N.M.) was examined as a drug for treatment of PT-GVHD using 4
      patients. RESULTS: N.M. was confirmed to inhibit cytotoxic activities of
      established cytotoxic T cell (CTL) clones in vitro. Simultaneously it was
      confirmed that fever and skin rash disappeared and liver function tests were
      normalized soon after the administration of N.M. in all four cases. Leukopenia
      and thrombocytopenia simultaneously improved. CONCLUSION: The effects of N.M.
      seem to be limited to inhibit cytotoxic activity of CTL. In addition to this
      drug, how to remove the CTL from the patients will be the essentially important
      theme for the future.

PMID- 10938970
TI  - Total quality management in blood transfusion.
AB  - Quality management is an ongoing development resulting in consistency products
      and services and ever increasing customer satisfaction. The ultimum is Total
      Quality Management. Quality systems and quality management in transfusion
      medicine have gained considerable attention since the outbreak of the AIDS
      epidemic. Where product orientation has long been applied through quality
      control, Good Manufacturing Practice (GMP) principles were introduced, shifting
      the developments in the direction of process orientation. Globally, and
      particularly in the more industrialised world people and system orientation has
      come along with the introduction of the ISO9001 concept. Harmonisation and a
      degree of uniformity are needed to implement a universally applicable Quality
      System and related Quality Management. Where the American Association of Blood
      Banks (AABB) is the professional organisation with the most extensive experience
      in quality systems in blood transfusion, the European Union and the Council of
      Europe now are in the process to design a quality system and management
      applicable to a larger variety of countries, based on a hybrid of current GMP and
      ISO9001 principles. The International Federation of Red Cross and Red Crescent
      Societies has developed a more universally to implement Quality Manual, with a
      pilot project in Honduras. It is recommendable to harmonise the various designs
      and bring the approaches under one common denominator.

PMID- 10938971
TI  - Haemovigilance and transfusion safety in France.
AB  - The risks associated to red cell and platelet transfusions are essentially bound
      to the polymorphism of blood group antigens and to transfusion transmitted agents
      including virus, bacterias.... In France, the haemovigilance system and several
      investigations allowed to measure these different kinds of risks. We also
      developed analysis of failures in order to prevent errors and accidents to
      increase blood safety.

PMID- 10938973
TI  - Getting people to give blood.
AB  - A well functioning blood service is dependent on people who are willing to come
      forward and give blood as a gift to those in need. This prerequisite brings a
      deeply human aspect to the blood service but also leaves it vulnerable to the
      fluctuations of people's donation behaviour, large or small as it may be, no
      matter is it lain in a developed metropolis or a remote African town. Blood
      services share a common concern: are they approaching a rising shortage of blood
      supply? Why does it take more effort than ever to get people to become blood
      donors? This lecture discusses donor recruitment as systematic work towards a
      blood supply, which is safe, adequate and reliable. Special attention is paid to
      the community, an individual's move from awareness to loyalty and demands on
      blood service personnel. The discussion is based on reports by those who have
      donor recruitment as full time profession and by those in other professions who
      have gained wide expertise in this field. It is human nature to feel needed,
      important and appreciated. Blood donation has all the possibilities to give these
      feelings to people. Any search for something new and exciting to motivate people
      to give blood must stem from a sound understanding of people in the community, an
      experience gained through years and a systematic working method.

PMID- 10938972
TI  - The Serious Hazards of Transfusion (SHOT) initiative: the UK approach to
      haemovigilance.

PMID- 10938974
TI  - Transferring donor loyalty to a new blood system operator: Hema-Quebec's
      experience.

PMID- 10938975
TI  - ICCBBA (International Council for Commonality in Blood Bank Automation).

PMID- 10938977
TI  - Institute of Medicine calls for boost in federal, state funding for immunization.

PMID- 10938976
TI  - Triptorelin approved for prostate cancer treatment.

PMID- 10938978
TI  - Report rates antiarrhythmic, antithrombotic choices for atrial fibrillation.

PMID- 10938979
TI  - Reducing prescribing errors through a quiz program for medical residents.

PMID- 10938980
TI  - The two faces of direct-to-consumer advertising.

PMID- 10938981
TI  - Coagulation products and their uses.
AB  - The indications, pharmacokinetics, and therapeutic guidelines for available
      coagulation products are reviewed. Patients with hemophilia, von Willebrand's
      disease (VWD), or acquired inhibitors to antihemophilic factor (AHF) cannot
      spontaneously stop an acute hemorrhage. Coagulation products used to manage
      bleeding in patients with these disorders include AHF concentrates, factor IX
      concentrates, factor VIIa concentrate, factor IX complexes, anti-inhibitor
      coagulant complexes, and desmopressin acetate. Typically, these commercially
      available products are used to manage acute bleeding or to prevent excessive
      bleeding during surgery. The dosage of the coagulation products and the duration
      of therapy depend on many variables, including the severity of the hemorrhage,
      the pharmacokinetics of the coagulation products, and patient-specific factors.
      Product purity and viral attenuation are also important considerations in
      determining an appropriate dosage regimen. Recombinant versions of some coagulant
      factors are available and can eliminate the risk of viral transmission. A
      thorough understanding of each coagulation product can guide product selection,
      dosing, and treatment duration and can reduce the risk of viral transmission.

PMID- 10938982
TI  - Economic model of sustained-release bupropion hydrochloride in health plan and
      work site smoking-cessation programs.
AB  - The development and application of an economic model designed to assess the
      specific costs and benefits of health plan coverage of smoking-cessation programs
      involving sustained-release bupropion hydrochloride are described. A cohort of
      100,000 employees or health plan members and 60,000 adult dependents was followed
      from the start of the model to either retirement at age 65 or death at age 85.
      The model was used to compare outcomes for coverage versus no coverage of
      sustained-release bupropion hydrochloride as a component of a smoking-cessation
      benefit under four managed care plan scenarios and four employer scenarios. For
      the managed care scenarios involving coverage of bupropion sustained-release the
      overall decrease in health care costs over a 20-year period ranged from $7.9
      million to $8.8 million; for every dollar spent covering smoking cessation, $4.10
      $4.69 in health care costs was saved. For the employer scenarios, health care
      costs over 20 years decreased by $8.3 million to $14.0 million, and smoking
      related indirect costs decreased an additional $5.1 million to $7.7 million; for
      every dollar spent covering smoking cessation, $5.04-$6.48 was saved. A model
      developed to assess the specific costs and benefits of covering sustained release
      bupropion hydrochloride as a component of a smoking-cessation benefit indicated
      cost savings for health plans and employers.

PMID- 10938983
TI  - Use of an Intranet to improve communication and manage knowledge in a large
      multisite pharmacy department.

PMID- 10938984
TI  - Compatibility of alatrofloxacin mesylate with commonly used drugs during Y-site
      delivery.

PMID- 10938985
TI  - Revised USP standards for product dating, packaging, and temperature monitoring.
AB  - Revisions in the standards of the United States Pharmacopeia (USP) related to
      product dating, packaging, and temperature monitoring are discussed. USP has
      revised product dating specifications as they relate to pharmacy practice.
      Pharmacists are required to affix beyond-use dates and not expiration dates to
      the prescription or repackaged vial. With respect to beyond-use dates for
      nonsterile products that are repackaged into unit dose or single-unit containers,
      the requirement has been changed from the previous period of six months from the
      date of repackaging or 25% of the time remaining until the expiration date,
      whichever is less, to one year. The type of packaging container, the material
      used in packaging, and the permeability of the container to moisture are
      important issues for pharmacists to consider. USP requires that the pharmacy
      facility where dispensing or repackaging occurs be maintained at controlled room
      temperature such that the calculated mean kinetic temperature does not exceed 25
      degrees C. USP standards for product dating, packaging, and temperature
      monitoring have changed, and pharmacists must educate themselves about these
      revisions.

PMID- 10938986
TI  - Pharmacy practice in Denmark.

PMID- 10938987
TI  - Epidemiology and pathogenesis of osteoporosis.
AB  - Osteoporosis is likely to become the most common disorder of our aging
      population. An understanding of factors that affect the incidence of osteoporosis
      is critical if we are to successfully minimize the impact of this disorder on
      morbidity, mortality, and the cost of health care. This article will provide an
      overview of the frequency, distribution, and consequences of the various types of
      osteoporotic fractures in different populations. We will discuss the major risk
      factors, emphasizing those that are reversible. Fracture risk not only involves
      abnormalities of bone mass and architecture, but also factors that affect the
      incidence of falls. The racial, ethnic, and geographic differences in fracture
      incidence are associated with parallel differences in bone mineral density (BMD),
      but the differences are often relatively small, suggesting that other
      architectural or metabolic differences in the skeleton make an important
      contribution. On the other hand, when combined with low BMD, multiple risk
      factors and comorbid conditions increase the risk of fracture as well as
      morbidity and mortality from fracture. Osteoporosis can result pathogenetically
      from inadequate peak bone mass, excessive bone resorption, or impaired bone
      formation. These can be affected by genetics, nutrition, lifestyle, systemic
      hormones, and local factors. The relative importance of these mechanisms is not
      fully understood and may differ among patients. Nevertheless, our current
      understanding of epidemiology and pathogenesis can help clinicians to develop the
      optimal approach to diagnosis and management.

PMID- 10938988
TI  - Differential diagnosis and secondary causes of osteoporosis.
AB  - Secondary osteoporosis refers to osteoporosis in which an underlying cause or
      factor other than those attributable to the postmenopausal state or aging can be
      identified. Primary, or idiopathic, osteoporosis implies that a secondary cause
      cannot be found. Secondary osteoporosis occurs not only in postmenopausal women
      but also in men and premenopausal women. In series reported from specialized
      centers, as many as 30% of postmenopausal women and 50% to 80% of men have an
      identifiable secondary cause of osteoporosis, although the frequency of secondary
      osteoporosis is probably much lower in the general population. In assessing the
      patient with osteoporosis, it is important to look for secondary causes and
      aggravating factors that are reversible and amenable to therapy. In addition to
      secondary forms, 2 metabolic bone diseases, osteomalacia and primary
      hyperparathyroidism, can mimic or aggravate osteoporosis. This paper will
      summarize the differential diagnosis and management of osteoporosis,
      osteomalacia, and hyperparathyroidism and review the most common causes of
      secondary osteoporosis.

PMID- 10938989
TI  - Diagnosis of osteoporosis.
AB  - Early diagnosis is the key to the prevention and treatment of osteoporosis. A
      healthy skeleton has intrinsic properties that confer strength to resist fracture
      under ordinary stress. Some of the properties that confer strength and fracture
      resistance include: bone mass or density and bone quality determined by skeletal
      composition, fine structure and spatial organization, geometric properties, and
      rate of remodeling. The current approach to early diagnosis of osteoporosis is
      based on the measurement of bone mass or bone mineral density (BMD). Low bone
      mass is the single most accurate predictor of increased fracture risk. BMD
      accounts for 70% to 80% of the future fracture risk in older white women and is a
      far better predictor of osteoporosis than hypertension is for stroke or total
      cholesterol is for cardiovascular events in men. Perhaps in the future a better
      understanding and quantification of bone quality will help refine our ability to
      identify patients at risk. BMD can be measured at a variety of skeletal sites
      using several different methods that have been approved by the FDA. The basic
      attributes of each method will be addressed in this paper, with particular
      attention given to the method that is currently considered the gold standard,
      dual energy x-ray absorptiometry. The indications for BMD testing, clinical
      utility of BMD, frequency of follow-up testing, correlation between the available
      densitometry methods, problems and pitfalls in interpretation, and features of a
      satisfactory densitometry report of results will all be addressed. The current
      role of biochemical markers of bone turnover in the diagnosis and monitoring of
      treatment will be discussed briefly.

PMID- 10938990
TI  - Prevention and treatment of osteoporosis.
AB  - Osteoporosis develops in older adults when the normal processes of bone formation
      and resorption become uncoupled or unbalanced, resulting in bone loss. Fractures
      are the result of decreased bone mass and strength and, in the case of wrist and
      hip fractures, usually involve a fall. Osteoporosis prevention and treatment
      programs should then focus on strategies that minimize bone resorption and
      maximize bone formation as well as on strategies that reduce falls. Optimal
      treatment and prevention of osteoporosis require modification of risk factors,
      particularly smoking cessation, adequate physical activity, and attention to
      diet, in addition to pharmacologic intervention. A number of pharmacologic
      options are now available to health care providers. This article focuses on US
      Food and Drug Administration--approved medications for osteoporosis and
      emphasizes the importance of using these agents as part of a comprehensive
      program that includes nonpharmacologic measures, complete diagnostic evaluation,
      and adequate follow-up with bone mineral density measurement.

PMID- 10938991
TI  - Osteoporosis in older men.
AB  - Historically, the focus in osteoporosis has been on postmenopausal women. In the
      past few years, information about osteoporosis in other populations, including
      men, has begun to emerge. Although less common in older men, osteoporosis
      nonetheless represents a major health concern. Approximately 30% of hip fractures
      worldwide occur in men, resulting in significant mortality and loss of
      independence. The incidence of osteoporotic fractures in men is increasing. The
      reason for this is unclear, but improvement in longevity and better management of
      other chronic diseases most likely play a role. Two recent studies have addressed
      the question of fracture risk in men past middle age and have estimated that men
      > 50 years of age have a 19% to 25% lifelong risk of osteoporotic fracture.
      Mortality is higher following hip fracture and pain is more intense in men than
      in women following severe vertebral fracture.

PMID- 10938993
TI  - Alterations in electromyograms due to inactivity-induced atrophy of the human
      muscle.
AB  - Regarding disuse atrophy, numerous investigations attempting to determine typical
      alterations of EMG measured with concentric needle electrodes have led to
      mutually inconsistent results concerning amplitude, duration, polyphasy, and
      number of spikes of motor unit action potentials. Our study comprises 21 patients
      with one-sided atrophy of m. quadriceps caused by immobilization and a control
      group of 19 healthy persons. Sufferers of myogenic, neurogenic or
      haemostasiological diseases as well as all persons on medication were excluded.
      Quantification of atrophy was performed by myosonography and measuring of
      circumferences. Both methods proved to be equivalent and more precise than
      computed tomography. Nearly all values of measurements in patients and in the
      control group remained within the normal range. But comparing EMG of atrophic m.
      vastus lateralis with the non-immobilized muscle of the other side revealed
      statistically significant differences in amplitude (14.1% higher in the atrophic
      muscle), duration (6.5% longer), number of phases (+13.2%) and spikes (+13.9%).
      In the healthy muscles of the control group we found no significant differences
      between dominant and non-dominant legs. Partly consistent and partly
      contradictory results in other studies may be explained by: a) too few cases
      examined, b) absence of control groups and/or c) omission of comparisons between
      right and left legs, but also d) by differences in applied normal values and e)
      by decreased innervation due to pain, swelling, contractures or arthrodeses. A
      very important factor was f) the duration of immobilization and g) the time
      elapsed between the end of immobilization and the examination.

PMID- 10938992
TI  - Manual cervical traction reduces alpha-motoneuron excitability in normal
      subjects.
AB  - The excitability of the Flexor Carpi Radialis alpha-motoneuron pool following
      manual cervical traction was assessed in twenty asymptomatic subjects, and
      compared to a hands only intervention. The excitability of the alpha-motoneuron
      pool was measured indirectly using the Hoffmann (H) reflex. H-reflex recruitment
      curves were taken to assess the number of alpha-motoneurons (alpha-motoneurons)
      firing in response to a given incremental increase in stimulation intensity. The
      rate of rise of the slope of the H-reflex recruitment curve (Hslp) was assessed
      using linear regression. Following manual cervical traction Hslp was
      significantly lower than pre-intervention trials. Manual cervical traction,
      therefore, reduced the excitability of the Flexor Carpi Radialis alpha-motoneuron
      pool. This effect was mediated by the central nervous system. There was no
      significant decrease in alpha-motoneuron excitability following the hands only
      intervention. Hslp was shown to be a more sensitive measure of changes in the H
      reflex than the more traditional parameter of Hmax/Mmax ratio and should be used
      in future studies of this nature.

PMID- 10938994
TI  - Distribution of muscle fiber conduction velocity of m. masseter during voluntary
      isometric contraction.
AB  - Muscle fiber conduction velocity (MFCV) is the velocity of an interference wave
      due to muscle fiber action potentials. In general, it has been reported that the
      value of MFCV in m. masseter is larger than that in limb and trunk muscles. But
      the values of MFCV in the reports were measured in part of the muscle, and the
      distribution of MFCV in the whole muscle including the end-plate and the tendon
      has not been measured. In this study, surface myoelectric signals are recorded in
      m. masseter during voluntary isometric contractions of 20, 30, and 40% MVC
      (maximum voluntary contraction) in eleven healthy male subjects with the use of
      array electrodes. The value of MFCV is found directly using an averaging method.
      The end-plate zone is concentrated in the lower quarter of the muscle. The
      distribution of MFCV depends on the location of the measured electrode. The
      largest value of MFCV of more than 20.0 m/s is obtained in the locations of the
      end-plate and the tendon. The minimum value of MFCV is obtained at the location
      of 10 mm measured from the end-plate along the direction of the muscle fiber to
      the tendon of the upper side. The mean values with the standard deviations during
      20, 30, and 40% MVC are 10.3 +/- 0.7, 11.6 +/- 0.7, and 12.2 +/- 0.8 m/s,
      respectively. The MFCVs between the different neighboring locations are compared
      and found to be significant by a level of 1% for each contraction level. The
      MFCVs increase depending on the contraction levels for various electrode
      locations on the muscle.

PMID- 10938995
TI  - Mechanomyographic investigation of muscle contractile properties in preadolescent
      boys.
AB  - The aim of the present study was to elucidate the muscle contractile properties
      of preadolescent boys using the mechanomyogram (MMG) and electromyogram (EMG). In
      8 preadolescent boys and 10 male young adults, the EMG and MMG were recorded from
      quadriceps muscles during isometric knee extension contractions at levels of 10
      to 80% MVC. The relationship of EMG and MMG to absolute force was approximated by
      a regression line (r > 0.8). The regression line of the EMG in preadolescent was
      located above that of the adults, whereas the MMG in both subject groups was
      fitted by virtually the same regression line. Thus, the MMG seems to be
      indicative of absolute force in preadolescents as well as young adults. Both
      groups showed a non-linear increase in the EMG and MMG with relative force
      (%MVC). The EMG and %MVC relationship was not significantly different between the
      two groups, whereas the MMG in preadolescents was smaller than that of adults
      over the range of force studied. The MMG increment with %MVC was more remarkable
      above 30 or 40% MVC in both groups; however, the rate of the increment in
      preadolescents was smaller than that in adults. The MMG and %MVC relationship
      suggests that the muscle contractile properties in preadolescent boys are
      characterized by immaturity of the fast twitch fibers.

PMID- 10938996
TI  - Effects of proximal and distal muscles' groups contraction and mental stress on
      the amplitude and frequency of physiological finger tremor. An accelerometric
      study.
AB  - Physiological finger tremor was assessed by two-dimensional solid accelerometry
      in 40 healthy normal subjects at rest (R) with the hand hanging over the armrest
      of a chair, in posture (P) with the arm rested on the armrest but the hand
      extended from the wrist, and finally adding proximal muscles contraction in
      extension (E) with the arm extended in front of the patient, each time with and
      without mental stress. The mean amplitude for physiological tremor, about 30
      microns, was almost doubled by hand extension and increased by 4 to 5-fold by arm
      extension with further increase by mental stress in each position, which gives a
      good estimation of the contribution of proximal and distal muscles into the
      amplitude of physiological tremor. There was no significant effect of age between
      20 and 60 years on tremor amplitude, but mean tremor frequency decreased
      significantly between 40 to 60 years. Mental stress increased amplitude but
      decreased tremor frequency of both across all position, possibly by increasing
      the synchronization of motor unit firing and by modifying the gain of the
      motoneurones and the stretch reflex as shown by electrophysiological studies.

PMID- 10938998
TI  - Ulnar-median and median-ulnar anastomoses in the forearm: a patient report.
AB  - Reports of an ulnar-median anastomosis in the forearm (UMAF) are rare and its
      existence has been questioned. A patient with clinical and electrophysiologic
      evidence of ulnar neuropathy at the elbow (UNE) had unexpected fibrillations in
      the abductor pollicis brevis muscle (APB). Additional nerve conduction studies
      suggested both ulnar-median and median-ulnar anastomoses in the forearm. The
      unexpected finding of APB fibrillations in a patient with UNE should raise the
      possibility of the rare UMAF.

PMID- 10938997
TI  - The origin of intermittent exhalation (A! Ha! Ha!) peculiar to human laugh.
AB  - Since Darwin (1872), the origin of the laugh with an intermittent exhalation "A!
      Ha! Ha!" which is peculiar to human, has been a great question. The author found
      out that this laugh is caused by the three sets of emotion. Firstly, light
      surprise or discovery. The ability to estimate "light" is absolutely important,
      because the amount of the first exhalation "A!" caused by the stimulation is
      decided by the amount of "surprise" felt by the subject. The ability to estimate
      the amount of "surprise" to be "light", makes the partial exhalation "A!".
      Secondly, consciousness of this harmlessness or delight, and thirdly, the
      following expectation of some safe circumstances. The author proved this theory
      by electromyography (EMG), photoplethysmography and galvanic skin reaction (GSR).
      The similarity between the facial EMG distribution pattern of "the beginning of
      laugh" and "the light surprise" was proved by electromyography about many facial
      muscles, with special fine electrode which did not disturb any natural facial
      expression of the subjects. Plethysmography and GSR proved light sympathetic
      tension and following relaxation when laughing. The author also suggests
      relationships between human laugh and human history such as the origin of
      clothing, language, and use of fire, which are specific in human.

PMID- 10939000
TI  - Interface of epidemiology and history: a commentary on past, present, and future.

PMID- 10938999
TI  - Role of central conduction time and motor evoked response amplitude in predicting
      stroke outcome.
AB  - Central motor conduction studies were done in 38 patients with first time
      unilateral cortical or sub-cortical stroke. Central conduction time and MEP
      amplitude were correlated with the percentage of change in the recovery score
      three months after stroke. A significant correlation was seen with recovery of
      muscle strength and the amplitude of the MEP. The study showed that central motor
      conduction studies would be a good tool for predicting stroke outcome.

PMID- 10939001
TI  - Coronary heart disease epidemiology in the 21st century.

PMID- 10939002
TI  - Epidemiology and prevention of stroke, now and in the future.

PMID- 10939003
TI  - New research directions in neuroepidemiology.
AB  - Many of the risk factors previously identified for disorders such as Alzheimer's
      disease, periventricular leukomalacia, multiple sclerosis, stroke, cerebral
      palsy, mental retardation, and acquired learning and attention disorders
      ultimately may be shown to damage the central and peripheral nervous systems
      through activation of inflammatory mediators. The challenge to epidemiologists in
      the future is to expand use of epidemiologic methods to explore how immune
      mediated insults produce CNS disorders in human populations. Studies of the
      association of use of nonsteroidal anti-inflammatory drugs with risk of
      Alzheimer's disease and those of the association of immune parameters with risk
      of cerebral palsy are excellent examples of how epidemiology can contribute to
      our understanding of the causes of neurologic and/or neurodevelopmental
      disorders. Many of the immune parameters of interest have short half-lives and
      are difficult to measure outside of the laboratory setting. Questions also remain
      as to the proper timing of measurements in relation to the initial insult and, in
      some cases, which tissue is the most appropriate to sample. These measurement
      issues will need to be resolved before use of immune biomarkers in epidemiologic
      studies of the etiologies of neurologic disorders can be fully realized.
      Epidemiologists are most likely to help identify ways to prevent neurologic
      disorders if they are knowledgeable about the molecular biology of inflammation,
      modulators of CNS vulnerability, and genetic polymorphisms that influence both
      inflammation and CNS vulnerability and are prepared to become adept at biomarker
      epidemiology. This does not necessarily compel them to gain extensive knowledge
      of neurobiology. Rather, neuroepidemiology in the 21st century will require
      increased collaboration between epidemiologists, neurologists, and
      neurobiologists.

PMID- 10939004
TI  - Epidemiology of mental disorders: the current agenda.

PMID- 10939006
TI  - Evolution of cancer epidemiology.

PMID- 10939005
TI  - Psychiatric epidemiology: progress and prospects in the year 2000.

PMID- 10939007
TI  - Infectious disease epidemiology in the 21st century: will it be eradicated or
      will it reemerge?

PMID- 10939008
TI  - Looking forward to 20/20: a focus on the epidemiology of eye diseases.
AB  - The encouraging scenario of international efforts to eliminate preventable and
      avoidable blindness is the legacy of public health ophthalmology in the 20th
      century. With active programs currently in place or beginning for the major cause
      of blindness in childhood and two of the leading infectious causes of blindness,
      it is natural that research in eye disease will shift even more heavily toward
      the leading causes of blindness in the older ages. The age-related eye diseases
      will rapidly become the most common causes of blindness and visual loss and, with
      the exception of cataract, are the more difficult to identify, diagnose, and
      treat. The human misery and social cost of blindness, especially in the countries
      that can ill afford it, are profound. To combat this problem, epidemiologic
      research in ophthalmology should look toward the following major areas: 1. the
      identification and testing of better screening modalities to determine early
      changes possibly amenable to preventive strategies. This includes detection of
      vitamin A deficiency as well. 2. the creation of uniform definitions for
      diseases, particularly glaucoma and early AMD, which have relevance for
      epidemiologic research into risk factors. 3. increased multidisciplinary
      research, working with investigators skilled in molecular genetics, biologic
      markers for age-related diseases, and those interested in new imaging and vision
      testing techniques. 4. ongoing work in clinical trials of new approaches to
      prevent or delay the onset of vision loss from eye disease, including future
      vaccines for chlamydia and onchocerciasis. The major public health issue of
      blindness prevention will not disappear in the next century but only shift
      emphasis to different causes if the current programs achieve the success that is
      hoped. Future epidemiologic research will continue to require a concerted,
      sustained, and multidisciplinary effort in order to contribute to the vision
      research agenda in the next century.

PMID- 10939009
TI  - Selected topics in the epidemiology of reproductive outcomes.
AB  - In summary, progress in research on reproductive epidemiology will depend on the
      increased use of biologic measurement, a focus on multiple outcomes, and an
      increased use of the couple or sexual network as the unit of study, with
      appropriate statistical methods for analysis of correlated data. The combination
      of these approaches holds great promise for research in the 21st century.

PMID- 10939010
TI  - Prenatal exposures and long-term health effects.

PMID- 10939011
TI  - Nutritional epidemiology issues in chronic disease at the turn of the century.

PMID- 10939012
TI  - Epidemiology of what to eat in the 21st century.

PMID- 10939013
TI  - Epidemiology of aging.

PMID- 10939014
TI  - Respiratory disease.

PMID- 10939015
TI  - Epidemiology of injuries: current trends and future challenges.
AB  - For the above challenges to be met, it will be important for the field of injury
      epidemiology to move from the largely descriptive studies that have predominated
      in the literature to the application of more rigorous analytical methods for
      defining the underlying casual patterns of injury. Studies focusing on the
      descriptive epidemiology of injury have and will continue to serve the field
      well, perhaps even more so than in other fields, since the proximal etiology of
      injuries (i.e., acute exposure to physical agents such as mechanical energy) is
      well known. However, major new advances in the prevention of injuries will
      continue to require a more analytical approach to understanding the complex array
      of factors that influence the incidence, severity, and outcomes of injury. At the
      same time, it will be important for investigators in this field to conduct
      rigorous evaluations of new interventions to better inform the establishment of
      programs and policies. These evaluations must include assessments of both the
      effectiveness and the costs of the intervention. For example, in a recently
      published systematic review of 10 different strategies for preventing motor
      vehicle injuries, 54,708 papers and reports were identified in the literature but
      only 161 met the initial screening criteria for inclusion in the published review
      (44). Of these, a much smaller number were randomized controlled trials or well
      executed controlled time series trials. Major advancements in the prevention and
      control of injuries will continue to rely on effective collaborations between
      epidemiologists and scientists from other disciplines, including the behavioral
      sciences, sociology, criminology, law, engineering, and biomechanics. Only
      through truly collaborative efforts across these disciplines will we be able to
      establish a foundation for cost-effective interventions. For example,
      understanding the principles of injury mechanics and the physical and physiologic
      responses of the human body to the impact of injury is fundamental to the study
      of injury causation (6). While significant advances have been made in this
      regard, more work needs to be done. The biomechanics of head injury are still not
      well understood, yet head injuries account for nearly 50 percent of all injury
      deaths and remain the leading cause of both injury death and disability among
      children and young adults. Animal and human cadaver research combined with
      rapidly evolving techniques of computerized modeling will continue to play a
      critical role in increasing our understanding of injury mechanisms. At the same
      time, the development of effective interventions is dependent on a better
      understanding of the role of behavior in injury causation and prevention (45). We
      know, for example, that the use of personal protective devices such as seat
      belts, car seats, and bicycle helmets reduces injury risk and that these
      behaviors can be influenced through educational, behavioral, and legislative
      strategies (46-49). Interventions addressing individuals at risk can be enhanced
      by additional research into risk perception, risk-taking, and behavioral
      responses to safety improvements. However, behavioral strategies may also be used
      effectively with key decision-makers who design and manufacture products and who
      pass and implement laws that affect the injury risk of entire populations; more
      research is needed to understand and influence the process of behavior change in
      these groups (50). The importance of injury as a major public health problem
      worldwide was highlighted in the seminal report "The Global Burden of Disease"
      (25). Worldwide, injuries account for approximately one in eight deaths among
      males and one in 14 deaths among females (51). Motor vehicle injuries alone
      constitute the ninth leading cause of disease burden as measured by the number of
      associated disability-adjusted life years (25). By the year 2020, motor vehicle
      injuries are projected to increase in rank to third. (ABSTRACT TRUNCATED)

PMID- 10939016
TI  - Interface of genetics and epidemiology.

PMID- 10939017
TI  - Statistics.

PMID- 10939018
TI  - Role of microbiology in epidemiology: before and beyond 2000.

PMID- 10939019
TI  - Update: spatial aspects of epidemiology: the interface with medical geography.

PMID- 10939020
TI  - Epidemiology of clinical medicine.

PMID- 10939021
TI  - Epidemiology and policy: the pump handle meets the new millennium.

PMID- 10939022
TI  - Epidemiology and social sciences: towards a critical reengagement in the 21st
      century.

PMID- 10939023
TI  - Management of health services: importance of epidemiology in the year 2000 and
      beyond.

PMID- 10939024
TI  - Ethics in epidemiology at the end of the 20th century: ethics, values, and
      mission statements.

PMID- 10939025
TI  - Individual risk prediction and population-wide disease prevention.

PMID- 10939026
TI  - Epidemiology and the World Wide Web: is there a 'net benefit?

PMID- 10939027
TI  - Vitamin 1,25-(OH)2 D3 concentrations in patients hospitalized long-term.
AB  - Vitamin D deficiency may be one reason for the onset and development of
      osteoporosis. The aim of the present study was to determine the occurrence rates
      of hypovitaminosis D in an unselected group of individuals presenting with common
      medical conditions and hospitalized for long periods. Concentrations of 1,25
      (OH)2 D3 were measured in 89 patients (38 males and 51 females). Mean age was 70
      years. Thirty-eight patients were tested in the spring and the remaining 51
      patients in the autumn. Vitamin D3 levels were significantly reduced in patients
      tested in the autumn (p < 0.001). The reason for this surprising observation may
      have been the small number of sunny days and the long hospital stays during the
      study period, differences in the composition of both groups and the fact that
      1,25-(OH)2 D3 reflects the actual vitamin D3 levels rather than those of its
      reserve in the human body. The results obtained suggesting hypovitaminosis D in
      an unselected group of elderly patients hospitalized with common diseases, even
      after the summer season, suggest the need for general supplementation of this
      vitamin throughout the year, regardless of the risk factors.

PMID- 10939029
TI  - Comparative study of the efficacy and tolerability of policosanol and lovastatin
      in patients with hypercholesterolemia and noninsulin dependent diabetes mellitus.
AB  - This randomized, double-blind study was undertaken to compare the efficacy and
      tolerability of policosanol (10 mg/day) and lovastatin (20 mg/day) in patients
      with hypercholesterolemia and noninsulin dependent diabetes mellitus. After 6
      weeks on a lipid lowering diet, 53 patients were randomized to receive either
      policosanol or lovastatin tablets that were taken o.i.d. for 12 weeks under
      double-blind conditions. Both groups were similar at randomization. Policosanol
      significantly (p < 0.001) lowered low-density lipoprotein (LDL)-cholesterol
      (20.4%), total cholesterol (14.2%) and the ratio of LDL-cholesterol to high
      density lipoprotein (HDL)-cholesterol (23.7%). Lovastatin significantly (p <
      0.01) lowered LDL-cholesterol (16.8%), total cholesterol (14.0%) and the ratio (p
      < 0.05) of LDL-cholesterol to HDL-cholesterol (14.9%). Triglyceride levels did
      not significantly change after therapy. Policosanol, but not lovastatin,
      significantly increased (p < 0.01) levels of HDL-cholesterol (7.5%). Comparison
      between groups showed that changes in HDL-cholesterol induced by policosanol were
      significantly greater (p < 0.01) than those induced by lovastatin. Both
      treatments were safe and well tolerated. Lovastatin moderately but significantly
      (p < 0.05) increased levels of aspartate aminotransferase, creatine phosphokinase
      and alkaline phosphatase. Adverse reactions were more frequent in the lovastatin
      group (p < 0.01) than in the policosanol group. In conclusion, policosanol
      administered at 10 mg/day produces more advantageous changes in HDL-cholesterol
      and has a better safety and tolerability profile than lovastatin 20 mg/day.

PMID- 10939028
TI  - Effects of policosanol and pravastatin on lipid profile, platelet aggregation and
      endothelemia in older hypercholesterolemic patients.
AB  - This randomized, double-blind study was undertaken to compare the effects of
      policosanol and pravastatin administered at 10 mg/day on lipid profile, platelet
      aggregation and endothelemia in older patients with type II hypercholesterolemia
      and high coronary risk. After 6 weeks on a lipid-lowering diet, patients with low
      density lipoprotein (LDL) cholesterol levels > 3.4 mmol/l were randomized to
      receive, under double-blind conditions, policosanol or pravastatin 10 mg tablets
      that were taken with the evening meal for 8 weeks. Policosanol significantly (p <
      0.00001) lowered LDL-cholesterol (19.3%), total cholesterol (13.9%) and the
      ratios of LDL-cholesterol/high-density lipoprotein (HDL)-cholesterol (28.3%) and
      total cholesterol/HDL-cholesterol (24.4%). Pravastatin significantly (p <
      0.00001) lowered LDL-cholesterol (15.6%), total cholesterol (11.8%) and the
      ratios (p < 0.0001) of LDL-cholesterol/HDL-cholesterol (18.9%) and total
      cholesterol/HDL-cholesterol (15.7%). Policosanol, but not pravastatin,
      significantly increased (p < 0.001) levels of HDL-cholesterol (18.4%) and reduced
      (p < 0.01) triglycerides (14.1%). Policosanol was more effective (p < 0.05) than
      pravastatin in inhibiting platelet aggregation induced by all agonists and it
      significantly reduced (p < 0.0001) platelet aggregation induced by arachidonic
      acid at 1.5 and 3 mmol/l by 42.2% and 69.5%, respectively, platelet aggregation
      induced by collagen 0.5 microgram/ml (p < 0.05) (16.6%) and that induced by
      adenosine diphosphate 1 mumol/l (p < 0.01) (20.3%). Pravastatin significantly
      reduced (p < 0.001) (27%) only platelet aggregation induced by arachidonic acid 3
      mmol/l. Both drugs significantly decreased (p < 0.00001) endothelemia levels but
      final values were significantly lower (p < 0.001) in the policosanol than in the
      pravastatin group. Both treatments were safe and well tolerated. Pravastatin
      significantly (p < 0.01) increased serum levels of alanine amine transferase but
      individual values remained within normal. Two patients on pravastatin
      discontinued the study because of adverse experiences (myocardial infarction and
      jaundice, respectively). In conclusion, the effects of policosanol (10 mg/day) on
      lipid profile, platelet aggregation and endothelemia in older patients with type
      II hypercholesterolemia and high coronary risk are more favorable than those
      induced by the same doses of pravastatin.

PMID- 10939030
TI  - Epirubicin 150 mg/m2-cisplatin versus epirubicin 180 mg/m2-cisplatin for advanced
      soft tissue sarcoma.
AB  - We have previously reported the superiority of the epirubicin 180 mg/m2-cisplatin
      combination over single drug epirubicin 180 mg/m2 for advanced soft tissue
      sarcoma both in terms of response (54% vs. 29%, p = 0.025) and survival (p =
      0.001). The aim of the present study was to establish whether decreasing the
      dosage of epirubicin to 150 mg/m2 would result in the same activity but with less
      hematological toxicity. One hundred fifty-nine patients with advanced soft tissue
      sarcoma were randomized for either epirubicin 150 mg/m2-cisplatin 120 mg/m2
      (group A) or epirubicin 180 mg/m2-cisplatin 120 mg/m2 (group B). The results were
      as follows: group A: 79 patients were evaluated. Overall response rate was 24/79
      (30%) (95% CI 21-41%). Median survival was 11 months and probability of survival
      at 1 year was 0.46. Grade IV granulocytopenia was present in 111/274 cycles and
      febrile neutropenia in 22/274. Group B: 73 patients were evaluated. The overall
      response rate was 39/73 (53%), (95% CI 42-64%). Median survival was 14 months and
      probability of survival at 1 year was 0.58. Grade IV granulocytopenia was present
      in 136/295 cycles and febrile neutropenia in 30/295. The differences were as
      follows: for overall response rate p = 0.004; power (for p = 0.05) 85%; for
      survival p = 0.09; for grade IV granulocytopenia p = 0.3; and for febrile
      neutropenia p = 0.61. A survival advantage (p = 0.043) was evident for patients
      randomized to group B and with performance status 0 or 1 compared with similar
      patients from group A. A plateau-like formation on the probability level of 0.26
      on the survival curve started from month 26 onwards. In conclusion, both regimens
      share the same toxicity but epirubicin 180 mg/m2-cisplatin seems more active in
      soft tissue sarcoma, possibly indicating a breakthrough for activity between an
      epirubicin dosage of 150 mg/m2 and 180 mg/m2 in combination with cisplatin. The
      superiority of the epirubicin 180 mg/m2-cisplatin regimen appears evident both in
      terms of response and survival.

PMID- 10939031
TI  - Mongolian gerbil (Meriones unguiculatus) as a model of cerebral infarction for
      testing new therapeutic agents.
AB  - Stroke mortality represents the third leading cause of death worldwide, after
      coronary artery disease and cancer. It has been demonstrated that in Mongolian
      gerbils, a unilateral hemispheric cerebral infarction can be produced following
      unilateral occlusion of the carotid artery because of the absence of connecting
      arteries between the basilar and carotid systems in these animals. The objective
      of this study was to comprehensively characterize the model of cerebral
      infarction in gerbil, clinically, biochemically and especially morphologically
      for prospective use in testing new therapeutic agents. Cerebral infarction was
      produced by ligation of the left common carotid artery in experimental gerbils.
      The control animals were sham-operated. One hour after surgery, 0.5 ml of 1%
      trypan blue was administered intraperitoneally to all animals. Initial clinical
      evaluations were made 8 h after surgery and every day thereafter for 30 days. On
      each of days 10 and 30, 4 animals were sacrificed. The degree of cerebral
      infarction was evaluated on the basis of clinical response, electrolyte and
      enzyme changes, vascular permeability of blood-brain barrier and morphological
      alterations. The total post-infarction mortality rate was 50%. The clinical
      symptoms presented as ipsilateral hemiparesis, ptosis of the eyelid, circling
      behavior, decreased breathing rate, decreased blood pressure and increased heart
      rate. Such symptoms developed within 8 h of ligation and persisted to sacrifice
      at day 30. Creatine kinase increased significantly on the 10th day and remained
      high to day 30. Increased potassium from the damaged cells and breakdown of the
      blood-brain barrier were first detected 72 h post-infarction. The morphological
      data showed evidence of brain cell necrosis, autolysis and phagocytosis 10 and 30
      days post-ligation in left hemispheres. Minor intercellular edema and some cell
      shrinkage was evident in the right brain. Areas of focal necrosis in the vicinity
      of blood vessels, especially in the left brain suggested a reperfusion injury as
      a consequence of minimal collateral reflow from the right brain into the left
      brain microvasculature. Experimental infarction in gerbil recreates the ischemic
      conditions causing stroke in humans. The animal model may be used for evaluating
      the efficacy of therapeutic agents that may ameliorate the condition in man.

PMID- 10939032
TI  - Pharmacology of cizolirtine: a new analgesic agent.
AB  - Cizolirtine citrate (E-4018) is a new analgesic agent with antinociceptive
      activity against phenylquinone (ED50 33.7 mg/kg) and acetic acid (ED50 24.4
      mg/kg) in mice, against acetic acid in rats (ED50 21.3 mg/kg) and in the plantar
      test (ED50 26.8 mg/kg). It demonstrated antinociceptive activity in the tail
      pinch and tail-flick tests (ED50s of 68.0 and 46.0 mg/kg, respectively), in both
      phases of the formalin test (ED50 13.8 and 2.31 mg/kg), and in the capsaicin test
      (ED50 7.14 mg/kg). Cizolirtine does not inhibit prostaglandin biosynthesis, it is
      not a ligand for opioid receptors, it does not have antiinflammatory or
      ulcerogenic activity, it has some antipyretic activity and shows no affinity for
      alpha 2-adrenergic receptors, but its analgesic effect was modified by idazoxan
      and by desipramine. Recent studies have shown that the analgesic effect of
      cizolirtine could be related, at least partially, to an inhibition of spinal
      substance P release.

PMID- 10939033
TI  - Biochemical studies of dopaminergic activation by stimuli of corn oil in the oral
      cavity in mice.
AB  - We investigated the effects of corn oil stimuli in the oral cavity on
      monoaminergic neurones by measuring the amount of monoamines and their
      metabolites in brains of mice. Intraoral injection of corn oil (0.1 ml) increased
      dopamine (DA) turnover rate in the cortex 3, 5 and 10 min after injection in
      mice. A significant increase of DA turnover rate was also observed in midbrain 10
      min after the corn oil injection. Turnover rates of noradrenaline (NA) and
      serotonin (5-HT) were not affected by the corn oil injection in any of the
      regions or times tested. In the chronic study, DA and 5-HT contents in the left
      and right cortexes and 5-HT contents in diencephalon in the chronic corn oil-fed
      group were significantly higher than those in the-control but NA contents were
      not significantly different between the two groups in all regions. In conclusion,
      the present results suggested that the stimuli of corn oil in the oral cavity
      might activate dopaminergic systems in the brain of mice and its chronic stimuli
      might increase DA contents in the brain. Although 5-HT contents increased in the
      brains of mice by the chronic corn oil intake, its physiological implication
      remains to be elucidated.

PMID- 10939034
TI  - Tolerance and withdrawal to anticonvulsant action of clonazepam: role of nitric
      oxide.
AB  - The use of clonazepam in the long-term treatment of epilepsy is greatly inhibited
      by its capacity to induce tolerance and dependence. A means of preventing or
      minimizing the tolerance and dependence inducing properties is required. Here the
      role of nitric oxide in preventing the development of tolerance and withdrawal
      hyperexcitability was studied. In Wistar rats, clonazepam at a dose of 0.25 mg/kg
      i.p. twice daily produced tolerance to its anticonvulsant action in 28 days.
      After sudden cessation of therapy it produced hyperexcitability. Tolerance was
      shown by a decrease in seizure threshold to near control value while withdrawal
      hyperexcitability was evidenced by a significant decrease in seizure threshold
      below the control value. L-Arginine (a donor of nitric oxide) and N omega-nitro-L
      arginine (an inhibitor of nitric oxide synthase) were given in doses of 150 mg/kg
      and 8 mg/kg, respectively on day 1, 3, 7, 14, 21 and 28 with clonazepam.
      Withdrawal hyperexcitability was seen on day 1, 2 and 4 after cessation of drug
      therapy. Electroshock was used as a model of epilepsy and seizure thresholds were
      determined by an up and down method of Kimball et al. L-Arginine was found to
      inhibit the development tolerance as well as withdrawal hyperexcitability when
      administered with clonazepam while N omega-L-arginine did not prevent either the
      development of tolerance or withdrawal hyperexcitability in the electroshock
      model. In the PTZ model, however, L-arginine had no effect on the anticonvulsant
      action and withdrawal hyperexcitability while inhibition of nitric oxide
      synthesis prevented withdrawal hyperexcitability in PTZ-induced seizures.

PMID- 10939036
TI  - Usefulness and safety of theophylline injection form (Theodrip) for the treatment
      of acute asthma.
AB  - The effects of the speed of intravenous infusion on the pharmacokinetics of
      theophylline were studied in 9 healthy volunteers (Ex I). Subjects were
      intravenously administered either six 4.8 mg/kg theophylline (Theodrip, Nikken
      Chemicals Co., Ltd., Japan) or three matching placebo injections (4.8 ml/kg
      physiological saline) for 30 min (Step I) or for 15 min (Step II). In Steps I and
      II, Cmax was 10.8 +/- 1.1 and 10.8 +/- 0.8 micrograms/ml, respectively. These
      Cmaxs were concentrations yielding therapeutic effects in patients with acute
      asthma. Next, comparative pharmacokinetics between theophylline (Theodrip) and
      aminophylline were examined by a crossover method in 16 healthy volunteers (Ex
      II). The 90% confidence limits of the differences of mean values were within 80
      120% and were 92.8-100.1% for Cmax, 99.7-105.3% for t1/2 and 100.2-104.4% for
      AUC. Thus, we concluded that the pharmacokinetics of the plasma theophylline
      after intravenous administration of Theodrip (theophylline at 4.8 mg/kg) were
      bioequivalent to those of aminophylline (6.0 mg/kg) for 30 min. In Ex I and II,
      no subjects had adverse effects and in Ex I no influence on ECG was seen. In
      addition, the convenience of Theodrip was compared with that of ampules of
      aminophylline among nurse volunteers (Ex III). The times required for set-up of
      Theodrip were significantly shorter than those of aminophylline ampules. On the
      other hand, the adverse reactions to aminophylline resulting from
      hypersensitivity reactions to its ethylenediamine component have been reported.
      Theodrip consists of 200 mg theophylline and 200 ml physiological saline in a
      plastic bag. Therefore, Theodrip, which does not contain ethylenediamine, is
      expected to have less adverse effects and be easier to handle than aminophylline.

PMID- 10939035
TI  - Theophylline in snoring and sleep-related breathing disorders: sleep laboratory
      investigations on subjective and objective sleep and awakening quality.
AB  - The aim of the present investigation was to comparatively examine the effect of
      theophylline on various sleep-related breathing disorders of different severity.
      In a single-blind, placebo-controlled crossover study, 30 patients were
      polysomnographically diagnosed as suffering from primary snoring (n = 7),
      obstructive snoring (n = 12) or moderate sleep apnea (n = 11). Subsequent
      polysomnographic investigations included one baseline, one placebo and one
      theophylline (Respicur retard 400 mg, Byk Gulden, Konstanz, Germany) night.
      Subjective sleep and awakening quality was evaluated by means of a test battery
      completed in the morning. Concerning respiratory variables, theophylline was most
      effective in patients with moderate sleep apnea. Obstructive snorers only showed
      a tendency towards improvement and primary snorers remained unchanged. Sleep
      architecture generally remained unchanged in all three patient groups. Objective
      awakening quality was partly improved in primary snorers, obstructive snorers, as
      well as in moderate sleep apnea patients as compared with baseline, but not as
      compared with placebo. Regarding subjective sleep and awakening quality, only
      primary snorers and obstructive snorers showed an improvement, as compared with
      baseline while moderate sleep apnea patients remained unchanged. Based on
      intergroup comparison, we conclude that patients with moderate sleep apnea showed
      the most pronounced improvement in regard to respiratory events. Concerning sleep
      initiation and maintenance, sleep architecture and subjective sleep and awakening
      quality, no significant intergroup differences were found. Regarding objective
      awakening quality, attention showed a significantly greater improvement in
      primary than in obstructive snorers and sleep apnea patients, while motor
      performance was most improved in obstructive snorers.

PMID- 10939037
TI  - A review of clinical use of theophylline in acute asthma: factors influencing
      kinetic disposition and drug interactions.
AB  - The clinical use of theophylline as a first line bronchodilator has declined
      during the last two decades. However, many therapeutic mechanisms for bronchial
      asthma have been discovered, and recent studies have suggested that theophylline
      therapy can play a beneficial role in the management of both chronic stable
      asthma and exacerbated disease treated in the emergency setting. In this article,
      the author describes the pharmacokinetics of theophylline and the major factors
      that influence the kinetics of the drug, such as physiopathological conditions
      and interactions with concomitantly administered drugs. Practical guidelines are
      then given on how to achieve optimal serum levels when planning theophylline
      therapy, including use of nomograms to decide loading and maintenance doses for
      nonsmoking adult asthmatic patients and adjustments for asthmatic patients with
      complications or on other drugs that may alter the kinetic disposition of
      theophylline.

PMID- 10939038
TI  - Seroepidemiologic study of herpes simplex virus type 2 and cytomegalovirus among
      young adults in northern Jordan.
AB  - Blood samples were randomly collected from 360 males and 390 females among
      apparently healthy university students aged 18-24 years and tested for herpes
      virus type 2 (HSV-2) and cytomegalovirus (CMV) antibodies. The prevalence of HSV
      2 seropositivity was 52.8% for males and 41.5% for females as detected by ELISA.
      On the other hand, the prevalence of CMV seropositivity was 75.6% in males and
      77.2% in females. The high percentage of seropositivity in our study is most
      probably due to the crowded living and low socioeconomic status of the Jordan
      population. The higher prevalence in males could be due to the way of life in the
      Middle East that gives males the freedom to play outdoors more than females.

PMID- 10939039
TI  - Cytoskeleton involvement during human cytomegalovirus replicative cycle in human
      embryo fibroblasts.
AB  - Several studies indicate that viruses can induce different cytoskeletal
      modifications. The present investigation examines the possible involvement of
      human embryo fibroblast cytoskeleton in the replication of human cytomegalovirus
      (HCMV). Significant cytoskeletal modifications occur in infected cells;
      specifically, microfilament depolymerization is observed very early during the
      HCMV replicative cycle, whilst microtubules and intermediate filaments do not
      undergo any change for longer times after infection. Our data focus, in
      particular, on microfilament depolymerization, which starts within the first hour
      of the replicative cycle, and on the significance of this event, as a CMV-induced
      mechanism to modify the post-transcriptional regulation of cellular gene
      expression for its own benefit. Among the possible mechanisms exploited by HCMV
      to induce microfilament modifications, one might involve the cellular ADP
      ribosylation activity, which is increased by HCMV very early in the infectious
      cycle. Experiments carried out on HCMV-infected cells, in the presence of ADP
      ribosylation inhibitors, seem to confirm this hypothesis.

PMID- 10939040
TI  - Isolation and identification of a calicivirus from a dog with diarrhoea.
AB  - The isolation and the characterisation of a calicivirus strain (213/95) from a
      dog with diarrhoea are reported. The virus grows only in cell cultures of feline
      origin (Crandell Feline Kidney Cells), and in neutralisation test the isolate
      demonstrated a slight antigenic correlation with the reference feline calicivirus
      strain (FCV-F9).

PMID- 10939042
TI  - HSP and apoptosis in leukocytes from infected or vaccinated animals by Brucella
      abortus.
AB  - The production of hsp and apoptosis of leukocytes in the peripheral blood of
      animals naturally infected with Brucella spp or treated with the vaccine Brucella
      abortus 19 have been investigated in this study. Cytokines able to induce
      phagocytic activity in macrophages of non treated healthy animals were found in
      the supernatant of bovine leukocytes cultivated in vitro. A long-lasting antibody
      response against hsp 60 kDa and 27 kDa, which lasts a long time, is induced in
      naturally infected animals, while in animals vaccinated with B. abortus 19 we
      detected an antibody response against hsp 60 and 70 kDa which is much shorter,
      disappearing in two months. During the early phase of infection, lymphocytes and
      monocytes of naturally infected animals show a delay of apoptosis in vitro
      compared to the same cells coming from healthy controls and vaccinated animals.

PMID- 10939043
TI  - Evaluation of tests employed in serological diagnosis of brucellosis caused by
      Brucella ovis.
AB  - A survey was carried out to verify the sensitivity and specificity of various
      tests (complement fixation test--CF; agar gel immunodiffusion--AGID; indirect
      enzyme linked immunosorbent assay--ELISA; immunoblotting--IB) employed in the
      serological diagnosis of brucellosis caused by Brucella ovis. The tests were
      executed on 44 blood serum samples of rams coming from B. ovis-free flocks, 75 of
      B. ovis experimentally infected rams and 1139 from rams living in flocks where B.
      ovis had been previously isolated. All tests were performed using B. ovis hot
      saline extract (HS) as antigen. Sensitivity results were 97.4% for IB, 98.68% for
      CF, 100% for AGID and ELISA; specificity was 100% for all methods. Concordance
      values were 89.62% (CF-AGID), 78.77% (CF-ELISA), 77.74% (AGID-ELISA), 65.45% (IB
      CF), 62.93% (IB-ELISA), 67.24% (IB-AGID). IB identified antibodies to antigenic
      components with molecular weight of 67, 63, 58, 55, 38, 35, 32, 30, 28, 25, 23,
      21, 20-18 kDa (proteins) and 15-12 kDa (rough lipopolysaccharide).

PMID- 10939041
TI  - Lyme borreliosis in central Italy (1995-1998).
AB  - From January 1995 to July 1998, 340 serum samples collected in Central Italy from
      patients clinically suspected of having Lyme borreliosis were investigated. All
      samples were tested for the presence of antibodies to B. burgdorferi by Elisa.
      The Elisa positive samples were subjected to further tests by Western Blot for
      confirmation. Out of 340 patients, 13 (3.8%) proved to be B. burgdorferi
      positive, while 9 (2.6%) were found to have Lyme disease with seroprevalence
      being higher in these latter than that of blood donors from Central Italy. Our
      results indicate that Lyme borreliosis is present in Central Italy. A comparison
      between Italian and European studies reveals that Lyme disease is still
      underestimated in Italy, the main reason being that a monitoring system for the
      study of Lyme borreliosis was only established in 1990.

PMID- 10939044
TI  - In vivo and in vitro assessment of the virulence of Listeria monocytogenes
      strains.
AB  - To evaluate whether the in vitro model (invasion and intracellular growth in Caco
      2 cells) for determining virulence is a suitable alternative to the in vivo model
      (50% lethal dose), we compared the levels of virulence obtained with the two
      models. We tested L. monocytogenes strains isolated from food and clinical
      samples during three episodes of listeriosis occurring in Italy in the period
      1993-1995. We also tested L. monocytogenes strains isolated from food during
      official control activities. The results obtained from the tested strains varied
      according to the experimental method adopted: the L. monocytogenes strains
      featuring the same genetic pattern showed a greater uniformity of response in
      vivo than in vitro. We can conclude that the in vitro model may be used as an
      alternative to the animal model to determine Listeria spp pathogenicity, though
      it cannot distinguish levels of virulence within the L. monocytogenes species.

PMID- 10939045
TI  - Bacterial pollution of Messina coastal waters: a one year study.
AB  - A year's monitoring of faecal pollution of marine coastal waters surrounding
      Messina was carried out in 1996/97. The distribution of faecal coliforms was
      evaluated in 15 stations located along the Sicilian coastline, sampled monthly in
      coincidence of the two opposing current phases ("montante" and "scendente"
      currents) which characterise the Straits of Messina. The data obtained provided a
      complete picture of hygienic-sanitary conditions of the area and highlighted the
      presence of heavily polluted sites in correspondence with river outflows. Higher
      bacterial counts were associated with lower salinity values and higher ammonia
      concentrations; over an annual study, they occurred during the coldest months,
      showing the negative impact of continental water inputs on the bacteriological
      quality of coastal waters.

PMID- 10939046
TI  - Purification of daptomycin binding proteins (DBPs) from the membrane of
      Enterococcus hirae.
AB  - Daptomycin binding proteins (DBPs) are membrane proteins which act as daptomycin
      targets. Daptomycin is a cyclic lipopeptide antibiotic which is active against
      Gram-positive bacteria and was shown to be the first inhibitor of lipoteichoic
      acid (LTA) synthesis. It was found that the antibiotic did not penetrate the
      bacterial cytoplasm but bound membranes with a non-covalent bond and in
      particular some proteins which were called DBPs. DBPs were indicated as enzymes
      involved in LTA synthesis whose binding and inhibition by daptomycin is
      responsible for the observed effect on bacterial LTA synthesis. The purification
      of DBPs will make it possible not only to shed light on the biosynthesis of the
      cell wall polymer but will also provide innovative targets for selection of new
      antibacterial compounds. In this study, the purification of DBPs is described.
      Affinity chromatography was used with daptomycin as the ligand. Final elution of
      DBPs from daptomycin-coupled resin was performed using either 0.1% SDS or 3 M
      NaCl. Polyacrylamide gel electrophoresis of the eluted protein fractions
      consistently showed four protein bands (ranging from 55 to 66 kDa) in
      denaturating conditions and two protein bands (60 and 66 kDa) in non-denaturating
      conditions. Isoelectrofocusing analysis of the same sample consistently revealed
      two bands with pIs around 5. That these purified proteins were really the desired
      DBPs is demonstrated by the retention of daptomycin-binding capability they
      displayed.

PMID- 10939047
TI  - Molecular epidemiology of Pseudomonas aeruginosa from cystic fibrosis in Sicily:
      genome macrorestriction analysis and rapid PCR-ribotyping.
AB  - This study addresses the epidemiologic relatedness of a collection of Pseudomonas
      aeruginosa isolates from cystic fibrosis patients attending the Pediatric Clinic,
      Catania, Sicily. Genome macrorestriction analysis after pulsed field gel
      electrophoresis (PFGE) was used to characterise all strains. Furthermore, a rapid
      typing procedure, developed in this study, based on polymerase chain reaction
      amplified ribosomal DNA spacer polymorphisms (PCR-ribotyping), straight from
      bacterial cultures, was used. On the basis of macrorestriction analysis after
      PFGE, persistence of infection was shown in all patients; two cross-transmission
      episodes were identified in the nosocomial as well as in the familiar
      environment. PCR-ribotyping proved to be useful for a DNA-based identification
      test, suitable for screening purposes. The rapid amplification protocol here
      tested is proposed to evaluate the discriminatory power of other specific target
      sequences in PCR-based typing assays, for epidemiologic purposes.

PMID- 10939048
TI  - Candida albicans strain differentiation in complete denture wearers.
AB  - Strain differentiation of 66 clinical isolates of Candida albicans obtained from
      healthy dentate and complete denture wearers was performed. Resistogram method
      based on differences in the resistance of C. albicans isolates to sodium
      selenite, boric acid, cetrimide, sodium periodate and silver nitrate was used for
      strain differentiation. Of the 32 potential strains that can be distinguished, 14
      different resistogram strains of C. albicans were found among the 66 isolates
      tested. Strain-C--was the most predominant (24.3% of total isolates), while
      strain A-CDE was the least predominant (1.5%). The results showed no particular
      association of certain strains with Candida infections in complete denture
      wearers. Sensitivity to antifungal agents showed that isolates from different
      strains were most sensitive to amphotericin B and nystatin and least sensitive to
      miconazole.

PMID- 10939049
TI  - Search for malaria parasites by PCR and Southern blot in patients with imported
      malaria in Italy.
AB  - The present study evaluates the sensitivity, specificity and usefulness of a PCR
      method with Southern blot hybridization to detect malaria parasites in blood
      samples from subjects with a suspect clinical diagnosis of malaria imported to
      Italy. Plasmodia were detected by PCR using a genus-specific primer-set
      corresponding to the sequences common to P. falciparum, P. vivax, P. malariae and
      P. ovale, as described by Arai (Arai et al., Nucleosides Nucleotides, 1994, 13,
      1363-1364) and Kimura (Kimura et al., Journal of Clinical Microbiology, 1995, 33,
      2342-2346). In addition, four distinct tandemly repetitive species-specific
      probes, described by Kawai (Kawai et al., Analytical Biochimestry, 1993, 209, 63
      69), were synthesized to specifically detect the four malaria parasites species
      by Southern blot hybridization. Fifteen blood samples from 12 patients (7 with
      malaria) were tested and the genus-specific PCR method showed a sensitivity of
      100% and a specificity of 100%, when compared to microscopy, in detecting malaria
      parasites in the tested blood samples. Fourteen samples (nine were positive and
      five negative by PCR) were confirmed by Southern blot, whereas only one P. vivax
      positive sample was not hybridized with the species-specific probes. We conclude
      that this PCR method with Southern blot hybridization may be useful in detecting
      malaria parasites in patients with malaria imported to Italy.

PMID- 10939050
TI  - Discrimination of tone durations across the menstrual cycle.
AB  - Discrimination of tone duration was studied as a function of menstrual cycle
      phase. In three phases of their menstrual cycle, 12 women compared the durations
      of 64 pairs of tones. They discriminated the tone durations least well in the
      premenstrual phase and tended to speed up their responding over sessions. In
      contrast, a control group of 12 men tended to improve their performance over
      sessions while response time remained constant.

PMID- 10939051
TI  - College students' performance on associated, corresponding tasks for
      horizontality.
AB  - 500 college biology students were asked to predict the axisymmetry (horizontal
      vertical position) of the water surface and a swimming goldfish in a masked,
      sealed container. Subjects were shown the fish submerged in the semifilled
      container before it was slipped into a terry cloth stocking. The researcher then
      asked subjects to predict the position of the fish and the water surface as the
      sealed container was rotated to different angles. Many college students did not
      understand that liquids and submerged organisms remain invariantly horizontal
      regardless of the rotation of the container.

PMID- 10939052
TI  - Differences in recognition and impressions of animate and inanimate objects in
      which features are deleted or added.
AB  - In the present study whether adults recognized features added to or deleted from
      an original pictures (asymmetric effects) when both animate and inanimate objects
      were presented together as stimuli, whether there was a difference in recognition
      between animate objects (butterflies and cats) and inanimate objects (artificial
      objects) and whether types of changes affected impression of pictures and
      impression predicted recognition were investigated. Ratings of Recognition and
      Impression were obtained. Analysis showed that adults discovered added features
      more accurately than deleted features in pictures of artificial objects,
      discovered deleted features more accurately than added features in pictures of
      cats, and there was no asymmetry of recognition in pictures of butterflies. There
      was difference in confidence ratings of recognition between animate and inanimate
      objects but no difference between them in percentage of correct recognition.
      Types of changes affected Impression ratings in all three types of objects.
      Moreover, Impression ratings predicted confidence ratings of pictures of cats and
      artificial objects but did not in pictures of butterflies. These results showed
      that asymmetry of recognition of addition and deletion is affected by the number
      of objects and whether they are animate or inanimate. Asymmetric recognition of
      additions vs deletions was sometimes mediated by Impression, both when one type
      of object was presented and when multiple types of objects were presented
      together.

PMID- 10939053
TI  - Factor structure of the Italian version of the WAIS-R compared with the American
      standardization.
AB  - Factor analysis for responses to the WAIS-R by 1,630 adults of the Italian
      standardization sample produced two factor solutions in different age groups, and
      showed high factorial similarity when compared with the same American solution.
      An estimate of g factor and variance components showed some difference with
      American data: a lower proportion of g and common variance, and a greater
      specificity characterized the Italian version with an almost identical error
      variance. For both the estimate of g and variance components some change across
      age groups was observed with g and common variance increasing and specific
      variance decreasing from youngest to oldest groups.

PMID- 10939054
TI  - Evidence of progressive delay of motor development in children with sensorineural
      hearing loss and concurrent vestibular dysfunction.
AB  - Gross motor development, and the effect of age, sex and vestibular function on
      it, was examined in 39 24- to 83-mo.-old children with sensorineural hearing
      impairment. Repeated testing was completed on 18 children. Delayed gross motor
      development was evident regardless of age, but only children less than 5 years of
      age had developmental balance deficits on initial testing. Both gross motor and
      balance development scores were lower on repeated testing. Furthermore,
      vestibular function scores facilitated identification of those children with a
      deficit in balance development as well as those with a progressive delay in motor
      or balance development. Implications for practice are discussed.

PMID- 10939055
TI  - Adults' and children's recognition of items added to or deleted from scenes:
      salience, complexity, and unnaturalness.
AB  - Adults' and children's recognition of additions to or deletions from scenes and
      variables affecting recognition of the salience, complexity, and unnaturalness of
      the alterations were studied. Stimuli were 8 pictures. Features were added to
      half of them, and features deleted from the other half. In another set of
      stimuli, the opposite types of alterations were made to the two groups of
      photographs. Subjects were shown the altered and unaltered pictures in pairs and
      asked if they were the same or not. Analysis showed that superiority of
      recognition for additions over deletions was not always observed because of an
      interaction with the salience of an item. The salience of an item more accurately
      predicted the percent recognition by adults than its complexity or unnaturalness.
      Although there were differences in percent recognition according to the type of
      alteration, the salience of items was nearly the same for adults and children.
      Similarities and differences in recognition by children and adults may be
      attributed to development.

PMID- 10939056
TI  - Tempo of background sound and performance speed.
AB  - 24 undergraduates performed a self-paced line tracing task. Fast music
      accelerated performance compared with slow music whereas the tempo of metronome
      tones did not affect performance.

PMID- 10939057
TI  - Sex differences and action scaling in overhead reaching.
AB  - Specifications of affordances is independent of the anthropometric scale of the
      perceiver. It is therefore predicted that sex differences disappear when
      perceptual performance is scaled relative to the relevant physical properties of
      the system formed by performer and environment in a particular action. 24 women
      and 30 men were compared for their ability to perceive the boundaries for
      overhead reaching for a ball suspended above them. Perceived and actual maximum
      action boundaries were measured in two height conditions, with and without
      wearing 15-cm high blocks under their feet. On average the men reached higher
      than the women; however, when perceived maximum reachable height was expressed as
      a ratio of actual maximum reachable height, the difference between the groups
      disappeared. The participants showed an identical fit between environment and
      performer in both height conditions. The results indicate that the specification
      of affordances for overhead reaching is independent of the height and the sex of
      the performer.

PMID- 10939058
TI  - Effect of the intensity of wireless telephone conversations on reaction time in a
      braking response.
AB  - Recently, concern has grown about the extent to which wireless telephone use by
      motor vehicle drivers constitutes a threat to traffic safety. This experiment
      investigated the effect of the intensity of wireless telephone conversations on
      reaction time (RT) for a braking response. Using a laboratory station to mimic
      the foot activity in driving, 16 adults were instructed to release the
      accelerator pedal and depress the brake pedal as quickly as possible following
      the activation of a red brake light. Mean RT was measured for 5 conditions which
      manipulated the intensity of a conversation, i.e., demand for attention,
      conducted on a wireless telephone. Analysis indicated that wireless telephone use
      caused a decrement in RT, however, there was no significant effect associated
      with intensity of the conversation across intensity.

PMID- 10939059
TI  - Stability of the Iceberg Profile as a function of perceived difficulty in
      defeating an opponent.
AB  - 9 starters and 8 nonstarters of a university women's softball team completed the
      Profile of Mood States prior to playing the team perceived to be the most and
      least difficult to defeat in their conference. A significant interaction
      indicated that nonstarters displayed higher fatigue prior to playing the opponent
      perceived as most difficult to defeat. In addition, significant mean differences
      were found between starters and nonstarters on constructs of Anger, Confusion,
      Tension, and Depression, suggesting that nonstarters may not share same
      psychological profile as their peers who start.

PMID- 10939060
TI  - Measurement of upper and lower body strength and its relationship to underhand
      pitching speed.
AB  - This study investigated the possible relationship for legs, arms, shoulders, and
      grip strength with underhand throwing speed. 40 female subjects had their legs,
      arms, and shoulder strength measured using a multipurpose exercise machine for
      assessing resistive force. Grip strength was measured using a handgrip
      dynamometer. Underhand throwing speed was measured with a radar gun. Regression
      analysis indicated a relationship (p < or = .05) between strength of the arms and
      underhand pitching speed. No significant relationships were found for legs,
      shoulders, and grip strength, and underhand pitching speed.

PMID- 10939061
TI  - Measurement of nonverbal receptive abilities in medical students.
AB  - Physicians have been reported to have difficulty in communicating with their
      patients. An element of this communication gap is proposed be related to the
      educational curriculum and the selection process of medical schools, in
      particular, with the emphasis on scientific methodology reducing exposure to
      humanistic values. This hypothesis was tested by measuring nonverbal receptive
      abilities in two groups. 30 medical students were compared with 30 college
      students who were not science majors but were age-, sex- and race-matched. The
      nonscience majors were better at perceiving nonverbal cues than medical students.
      Male nonscience majors had higher scores than male medical students while similar
      results were seen when female nonscience majors were compared with female medical
      students. Finally, medical students planning to practice as primary care
      specialists had higher scores than those interested in specialties which do not
      involve direct or prolonged patient care.

PMID- 10939062
TI  - Study habits and anxiety about learning foreign languages.
AB  - The purpose was to investigate the relationship of self-reported study habits to
      anxiety about learning foreign languages. 219 college students from a variety of
      disciplinary backgrounds were enrolled in either Spanish, French, German, or
      Japanese classes. Correlational analyses, using the Bonferroni adjustment,
      indicated that students with the highest anxiety about foreign languages tended
      to report that (1) they spend too much time on some subjects and not enough time
      on others, (2) they frequently do not get enough sleep and feel sluggish in class
      or when studying, (3) they do not try to space study period to avoid becoming too
      tired while studying, and (4) they have trouble settling down to work and do not
      begin to study as soon as they sit down. The implications of these findings are
      discussed.

PMID- 10939063
TI  - Speech self-monitoring in preschoolers: the effects of delayed auditory feedback
      on recitation.
AB  - 39 3- to 6-yr.-old children counted to 10 or recited the alphabet with normal
      auditory feedback, and delays of 150, 350, and 550 msec. There were no age
      differences. In addition to affecting rate of speech, delay differentially
      influenced the prosody, intelligibility, and content of utterances. For both
      tasks and all delay intervals, delay slowed speaking and produced more prosodic
      disturbances than no delay. More disturbances of intelligibility occurred at the
      350- and 550-msec. delays than under no or 150-msec. delay. Disturbances in the
      content of counting were greater than in the no-delay condition but did not
      differ across delays. For alphabet recitation, disturbances in content under
      delay were greater than under no delay and were greater at 350 and 550 msec. than
      at 150 msec. Thirty-four children lost track of what they were doing; 10
      articulated confusion. Children as young as 3 years of age concurrently self
      monitor their speech for content.

PMID- 10939064
TI  - Effects of listening to Mozart and Bach on the performance of a mathematical
      test.
AB  - The purpose of the current study was to assess the effect of listening to Mozart
      and Bach on the immediate performance of a 10-min. mathematical test. The study
      consisted of 61 undergraduate participants. Participants were randomly assigned
      to a control group, a Mozart group, or a Bach group. Participants were then
      administered a mathematics pretest, listened to a selection of music for 10 min.,
      and were then administered a mathematics posttest. The test was constructed to be
      similar to items taken from the University Mathematics Placement Examination.
      Analysis indicated no significant effect on the immediate mathematics test when
      participants listened to 10 min. of either Mozart or Bach. These findings suggest
      caution in measuring differences in various cognitive tasks as indicating
      increases in intelligence scores.

PMID- 10939065
TI  - Measuring development of a child's early walking: implications for clinical
      assessment of gait.
AB  - This study examined the three-dimensional kinematics and motor development
      patterns in early walking gait longitudinally over 8 mo. and presents an example
      of walking development of one normal child which might be used for comparative
      purposes in the clinical assessment of gait.

PMID- 10939066
TI  - Perceptions of aging and their relation with age, death depression, and sex.
AB  - The relations of knowledge and attitudes about aging to one's age, sex, and
      depression about death were examined. 111 undergraduate and graduate students
      completed the multiple-choice form of the Facts on Aging Quiz and the Death
      Depression Scale. Present results extend previous research showing that people's
      perceptions of aging change with age. How such perceptions change is twofold: (1)
      perceptions of aging do not become more positive with age but do have less
      negative bias, and (2) they show more knowledge of aging on test measures. No sex
      differences were found in knowledge and attitudes about aging. No significant
      relationship was found between scores on measures of attitudes toward aging and
      depression about death. Sex differences were found on scores for death
      depression, with women reporting greater depression about death.

PMID- 10939067
TI  - An alternate short form of the Speech-Sounds Perception Test.
AB  - A short form of the Speech-Sounds Perception Test based on the last three series
      is presented. For the total sample of 632 the KR-20 reliability was .84. An age-
      and education-corrected standardized score formula is provided. Reliability
      coefficients and descriptive statistics are presented for three groups, 107
      normal, 150 diffusely brain-damaged, and 310 undiagnosed patients sent for
      assessment plus 65 volunteers for the normal group.

PMID- 10939068
TI  - Relationship among body image, sex, and popularity of high school students.
AB  - Body dissatisfaction and attempts to lose weight are increasingly common among
      adolescents. Research has identified a number of factors significantly associated
      with body image, including sex, media, parental relationship, and puberty as well
      as weight and popularity. It was hypothesized that popular adolescents would have
      greater body dissatisfaction, more body distortion, and lower body esteem. From a
      rural high school 116 10th and 12th grade students were surveyed. Two teachers
      from the school also completed a Body Image Figure scale for each student.
      Subjects rated each grade member on a 5-point Likert-type scale, indicating how
      much they liked the classmate. A Social Preference rating (Popularity) was
      calculated for each subject from these ratings. Each subject also completed a
      Body Image Figure scale and Body Esteem scale. Body distortion was calculated by
      comparing the teachers' and a student's responses. Significant sex differences
      were found for scores on body satisfaction, distortion, and esteem, but none for
      popularity with distortion and body esteem. A relationship between popularity and
      body satisfaction was found, with the most popular adolescents reporting the
      least discrepancy between their ideal body image and their current body image.
      Popular adolescents are most satisfied with their body type.

PMID- 10939069
TI  - Use of popular dream literature.
AB  - The present study investigated ratings of popular books on dream interpretation.
      Books were rated as helpful, especially those including explicit guidelines for
      working on dreams.

PMID- 10939071
TI  - Predicting participation in noncompulsory physical education: do goal
      perspectives matter?
AB  - The purpose of this study was to examine relationships between personal and
      situational achievement goals and participation in an optional physical education
      program, utilising a prospective design. Pupils (N = 123) in their final year of
      compulsory schooling completed measures assessing goal orientations, perceptions
      of the motivational climate of their physical education class, perceived
      competence, and enjoyment of physical education. Those pupils (N = 76) who
      continued their full-time education at a sixth form college were later surveyed
      to determine whether they participated in physical education at college.
      Hierarchical discriminant function analysis showed that discrimination was
      possible between participants and nonparticipants in college physical education
      on perceptions of a prevailing mastery climate and enjoyment. Goal orientations,
      perceptions of a prevailing performance climate, and perceived competence did not
      contribute reliably to group separation. Participants at college were more likely
      to perceive a mastery environment and to enjoy lessons more than students who
      chose not to take part. These findings underscore the importance of promoting
      mastery-based criteria for success in classes, along with positive emotional
      reactions, if teachers wish to maximise involvement in noncompulsory physical
      education.

PMID- 10939070
TI  - The WWW as a research medium: an illustrative survey on paranormal belief.
AB  - Data collected with a short World Wide Web (WWW) survey on paranormal belief,
      age, sex, locus of control, extraversion, emotional and physical well-being, and
      mood were compared with findings from recent literature while controlling for
      effects of self-selection. Each variable was measured with one item. The sample
      comprised 342 women, 648 men, and 8 participants of unknown sex, of whom 76.7%
      were self-selected and 23.3% did not select themselves. There was a weak but,
      given the large sample, significant effect of self-selection regarding paranormal
      belief (rpb 932 = .08) but no relationships for paranormal belief and the
      examined variables. In the entire sample, statistically significant correlations
      ranging from .13 to .07 between paranormal belief and female sex, scores on
      external locus of control, good mood, extraversion, and emotional well-being
      corresponded with previous offline results.

PMID- 10939073
TI  - Provision of enabling technology in professional sports.
AB  - Multiple-round golf tournaments are designed intentionally to separate
      individuals' scores as play proceeds. Variance analyses and consideration of
      individual differences (vs group mean effects) for a sample of professional
      events confirm that 3-, 4-, and 5-round tournaments show significantly increased
      variability (though stable means) from first to last rounds. It is argued here
      that the dispersion of scores increases as play proceeds because the more
      physically or mentally fit players emerge and continue to perform best.
      Furthermore, a marginal income analysis indicates that the average gain in
      earnings from a one-shot improvement in score is approximately $8,000. An
      interpretation based on fatigue, competition, and stress supports the
      Professional Golf Association's claim that provision of enabling devices, like a
      golf cart for disabled players, is also an enhancement and is thus unfair.

PMID- 10939072
TI  - Images of a familiar face do not capture attention under conditions of
      inattention.
AB  - Personally and emotionally meaningful information (e.g., one's own name) has
      shown to capture attention. The question we studied was whether an image of a
      familiar face draws attention even though it is not expected, and it appears when
      the focus of attention is directed to other stimuli. Observers' task was to
      compare two faces and report whether they were identical or left-right reversed.
      In addition to these faces, a matrix of 'background' faces was displayed. On
      noncritical trials, the matrix consisted of unfamiliar faces. On critical trials
      (in about every eighth trial) either an observer's own face or President
      Ahtisaari's face was displayed. Reaction time was nearly identical on the
      critical and uncritical trials. On the recognition test about half of the
      observers were certain that they had seen their own faces in the first part of
      the experiment. When explicitly asked, however, only three of 26 observers
      reported that they had recognized their own faces during the comparison task.

PMID- 10939074
TI  - Sophisticated and naive listeners' magnitude estimation scaling judgments of
      speech intelligibility and speech annoyance.
AB  - 15 women with formal training in speech and hearing sciences and 15 women with no
      formal training provided magnitude estimation scaling responses for the
      intelligibility and annoyance of audiotaped speech samples. Analysis indicated
      that both groups scaled intelligibility and annoyance the same. As samples became
      more unintelligible, they also became more annoying.

PMID- 10939075
TI  - The role of feedback in manual tracking of visual targets.
AB  - The role of visual feedback in manual tracking was investigated in 24 subjects
      who tracked 5-, 10-, and 40-mm/diameter targets, moving on a screen at 18 to 25
      mm/sec., along various paths, by moving an unseen handle over a digitizing
      tablet. A cursor indicating instantaneous handle position was visible at all
      times on half the trials and hidden within a circle coaxial with the target but
      double its diameter in the other half. The handle had to be within the
      instantaneous target's digitizer-defined boundaries for the latter to keep
      moving. All tracking movements were segmented into small movement steps. A
      tendency to outrun the target was seen, indicating predictive control. Absence of
      visual feedback had negligible effect on movement velocity. Movement direction
      appeared to involve open-loop programming but improved significantly when
      subjects could see the cursor. Occasional corrective movements occurred only when
      visual feedback was given. Otherwise, a large positional error accumulates
      despite reasonable ability to control tracking direction.

PMID- 10939076
TI  - The ropes and challenge course: a quasi-experimental examination.
AB  - In answering the call for empirical documentation of the effect of ropes and
      challenge course participation on the psychosocial function and sport performance
      of athletes and teams, exploratory studies have identified postcourse changes in
      group cohesion and approaches to sport competition. The purpose of the current
      study was to utilize a pretest-posttest comparison group design to expand
      knowledge in this area. 35 members of a girls' high school tennis team
      participated. The 16 individuals who participated in a preseason program and the
      19 individuals who did not comprised the treatment and comparison groups,
      respectively. Team members completed the Group Environment Questionnaire and the
      Sport Orientation Questionnaire four days prior to and two days after the course
      experience. A series of 2 x 2 analyses of variance, (group x time) run on each of
      the scales, gave a significant group x time interaction on one social cohesion
      scale but none for scores on the Sport Orientation Questionnaire. The findings
      are discussed in relation to research and the implementation of these programs
      with athletes.

PMID- 10939077
TI  - Language performance in three groups of children with sickle cell disease: those
      with stroke, without stroke, and at risk for stroke.
AB  - Language performance was assessed in three groups of children (16 boys and 14
      girls) with sickle cell disease: those with stroke, without stroke, and at risk
      for stroke. Scores of the three groups did not differ significantly on language
      comprehension, language expression, spatial orientation, or on overall combined
      performance scores. Such results have positive medical implications.

PMID- 10939078
TI  - Preliminary test of effects of cognitive ability, experience, and teaching
      methods on Verbal Analogy Test scores.
AB  - The methods from which one can choose when preparing for the GRE Verbal Analogies
      include books, software, audiotapes, and formal classroom instruction. What
      teaching method will work best for a given individual? To begin the search for an
      answer, Gray's test of reasoning ability was given to 28 undergraduates who also
      answered a questionnaire detailing their experience with analogies. They were
      randomly assigned to teaching conditions ranging from self-directed workbook
      study to intensive interactive assistance. No teaching method was superior
      overall, but interactions showed that (1) students who scored worst on the
      pretest improved the most, (2) those higher in cognitive functioning and
      experience performed better after intensive interactive assistance, and (3) those
      lower in both cognitive functioning and experience did significantly better with
      self-paced workbooks. This preliminary work suggests that it may be profitable to
      assess the prior experience and reasoning of potential students and adopt the
      methods for teaching formal operational thought found empirically to be most
      suitable.

PMID- 10939079
TI  - Typicality of objects in urban park scenes.
AB  - Typicality is a basic property of any categorization process, including the
      categorization of environmental scenes. We tried to judge whether a scene as a
      type of situation influences judgements about the typicality of elements when
      considering the part-whole relationship between the element and the scene. The
      subjects were asked to rate typicality on a scale of 1 to 7 and to give a word
      that defined the urban park elements appearing in a park scene or on a blank
      background. Some elements (wastepaper basket, fountain, street lamp, and statue)
      were depicted with two styles (classical and contemporary). The results indicate
      that the scene or blank background had no effect on the typicality scores but
      subjects had difficulty providing an appropriate word when elements with a
      contemporary style were shown on a blank background.

PMID- 10939080
TI  - Do left-handed competitors have an innate superiority in sports?
AB  - This study assessed handedness distributions among (a) sporting competitors (n =
      1,112) and nonsporting university students (n = 1,112), (b) sporting competitors
      engaging in interactive (n = 576) and in noninteractive sports (n = 536), and (c)
      sporting competitors engaging in direct interactive (n = 219) and indirect
      interactive (n = 357) sports. Chi-squared showed that there were statistically
      significant differences in proportions of left-handed persons in (a) sporting
      competitors and nonsporting university students, (b) sporting competitors
      engaging in interactive and noninteractive sports, (c) sporting competitors
      engaging in interactive sports and nonsporting university students, and (d)
      sporting competitors engaging in direct interactive and indirect interactive
      sports. It appears that left-handers are more common among those who engage in
      competitive manual activities. This superiority of the left-handers may be fully
      explained by a consideration of tactical or strategic factors associated with
      handedness during sporting interactions. The results with important implications
      for the measurement and evaluation of handedness are discussed in the light of
      the current findings on laterality.

PMID- 10939081
TI  - Current gender stereotypes and their evaluative content.
AB  - A sample of 173 undergraduate students rated 300 attributes to assess current
      gender stereotypes, and a second independent sample (n = 57) evaluated the
      favorability of these attributes. Statistical results indicated that the college
      students ascribed different attributes to men and women. Although the content of
      gender stereotypes seems to have remained unchanged over the years, the value
      attached to stereotypic gender traits seems to be changing. More specifically, a
      greater number of unfavorable attributes were used to describe men than women,
      thereby creating a more negative masculine stereotype.

PMID- 10939082
TI  - Image control and posttraumatic symptoms in children following SCUD missile
      attacks.
AB  - Based on previous studies reporting an association between high image control and
      low posttraumatic symptoms in adults exposed to a traumatic event, this study
      explored whether a high capacity for image control by children may serve as
      protective factor against the long-term effect of trauma. The sample consisted of
      39 children displaced due to the destruction of their homes after the missile
      attack on Tel-Aviv during the Gulf War. Analysis confirmed the hypothesis that
      low scores on the Test of Visual Image Control were associated with specific
      posttraumatic symptoms but not with general ones.

PMID- 10939083
TI  - Urban health: a new agenda?

PMID- 10939084
TI  - Air pollution and health in urban areas.
AB  - In this paper, recent reviews of the World Health Organization, other review
      papers, and more recent literature on the human health effects of current air
      pollution trends in urban areas are reviewed and summarized as follows: Sulphur
      dioxide. Some studies, but not others, found associations between sulphur dioxide
      (SO2) exposure and daily mortality and morbidity. Single-pollutant correlations
      sometimes disappeared when other pollutants, especially suspended particulate
      matter (SPM), were included. Cross-sectional studies with asthmatics revealed
      significant, non-threshold relations between SO2 and decrements of the forced
      expiratory volume in 1 second (FEV1). Nitrogen dioxide. Weak associations between
      short-term nitrogen dioxide (NO2) exposure from gas cooking and respiratory
      symptoms and a decrement in lung function parameters were found in children, but
      not consistently in exposed women. With long-term exposure, children, but not
      adults, exhibit increased respiratory symptoms, decreased lung function, and
      increased incidences of chronic cough, bronchitis, and conjunctivitis. A causal
      relationship between NO2 exposure and adverse health effects has not yet been
      established. Carbon monoxide. Binding of CO in the lungs with hemoglobin in the
      blood forms carboxyhemoglobin (COHb), which impairs the transport of oxygen. The
      health effects of CO include hypoxia, neurological deficits and neurobehavioral
      changes, and increases in daily mortality and hospital admissions for
      cardiovascular diseases. The latter persists even at very low CO levels,
      indicating no threshold for the onset of these effects. Whether the relation
      between daily mortality and exposure to CO are causal or whether CO might act as
      a proxy for SPM is still an open question. Ambient CO may have even more serious
      health consequences than does COHb formation and at lower levels than that
      mediated through elevated COHb levels. Ozone. Short-term acute effects of O3
      include pulmonary function decrements, increased airway responsiveness and airway
      inflammation, aggravation of pre-existing respiratory diseases like asthma,
      increases in daily hospital admissions and emergency department visits for
      respiratory causes, and excess mortality. Exposure-response relations are non
      linear for the respective associations between O3 and FEV1, inflammatory changes,
      and changes in hospital admissions, whereas the relation between percent change
      in symptom exacerbation among adults and asthmatics is linear. Single-pollutant
      associations between O3 exposure and daily mortality and hospital admissions for
      respiratory diseases is statistically significant, even in multi-pollutant
      models. Suspended particulate matter. Associations between SPM concentrations and
      mortality and morbidity rates are significant. The acute health effects of SPM,
      even at short-term low levels of exposure, include increased daily mortality and
      hospital admission rates for exacerbation of respiratory disease, fluctuations in
      the prevalence of bronchodilator use, and cough and peak flow reductions, as well
      as long-term effects with respect to mortality and respiratory morbidity. Such
      effects depend on particle size and concentration and can fluctuate with daily
      fluctuations in PM10 or PM2.5 levels. The relation between PM10 or PM2.5 exposure
      and acute health effects is linear at concentrations below 100 micrograms/m3.
      Currently no threshold has been reported below which no effects occur. The
      influence of co-polluting gaseous pollutants could explain part of the observed
      variance in short-term health effects and reduce the contribution of SPM. Lead.
      The biological effects of lead can be related to blood lead levels, the best
      indicator of internal exposure. The potential effects of lead in adults and
      children include encephalopathic signs and symptoms, central nervous system
      symptoms, cognitive effects, increased blood pressure, and reduced measures of
      child intelligence. (ABSTRACT TRUNCATED)

PMID- 10939085
TI  - Noise and health in the urban environment.
AB  - Noise, including noise from transport, industry, and neighbors, is a prominent
      feature of the urban environment. This paper reviews the effects of environmental
      noise on the non-auditory aspects of health in urban settings. Exposure to
      transport noise disturbs sleep in the laboratory, but generally not in field
      studies, where adaptation occurs. Noise interferes with complex task performance,
      modifies social behavior, and causes annoyance. Studies of occupational noise
      exposure suggest an association with hypertension, whereas community studies show
      only weak relations between noise and cardiovascular disease. Aircraft and road
      traffic noise exposure are associated with psychological symptoms and with the
      use of psychotropic medication, but not with the onset of clinically defined
      psychiatric disorders. In carefully controlled studies, noise exposure does not
      seem to be related to low birth weight or to congenital birth defects. In both
      industrial studies and community studies, noise exposure is related to increased
      catecholamine secretion. In children, chronic aircraft noise exposure impairs
      reading comprehension and long-term memory and may be associated with increased
      blood pressure. Noise from neighbors causes annoyance and sleep and activity
      interference health effects have been little studied. Further research is needed
      for examining coping strategies and the possible health consequences of
      adaptation to noise.

PMID- 10939086
TI  - Public health impact of large airports.
AB  - Large airports with the related infrastructure, businesses and industrial
      activities affect the health of the population living, travelling and working in
      the surroundings of or at the airport. The employment and contributions to
      economy from the airport and related operations are expected to have a beneficial
      effect, which, however, is difficult to quantify. More pertinent data are
      available on the, largely negative, health effects of environmental factors, such
      as air and soil pollution, noise, accident risk, and landscape changes.
      Information on the concurrent and cumulative impact of these factors is lacking,
      but is of primary relevance for public health policy. A committee of the Health
      Council of The Netherlands recently reviewed the data on the health impact of
      large airports. It was concluded that, generally, integrated health assessments
      are not available. Such assessments, as part of sustainable mobility policy,
      should accompany the further development of the global aviation system.

PMID- 10939087
TI  - Social determinants and inequalities in urban health.
AB  - Social and environmental factors are health determinants, in association with
      behavior, biological factors, and health services. Whereas socioeconomic
      characteristics (age, gender, ethnicity, social status) describe individuals,
      social determinants work through broader policies that are influenced by
      governments. The relation between health and four social areas is discussed.
      Social capital, measured as social networks and social support, appears to be
      protective in developing some heart disease and mental illnesses; job control at
      work is also found to protect against heart disease; early life experiences
      affect both biological and social development; and the degree of income
      inequality within societies correlates with health status. The Independent Report
      on Inequalities in Health, published in the United Kingdom in 1998, is also
      reviewed. The report (a) briefly describes inequalities in health by social
      class, sex, and ethnicity; (b) reviews the literature on policy areas that affect
      health; (c) includes a section indicating relatively little inequality of access
      or provision in the National Health Service; and (d) makes 132 recommendations.
      Social determinants is a new area of research having the potential to link
      epidemiology and environmental sciences at small area level.

PMID- 10939089
TI  - Health and home for homeless people in transition.
AB  - In recent years, increasing focus has been placed on the relation between
      environmental qualities and the promotion of well-being. This paper explores this
      relationship from an environmental psychological approach that emphasizes the
      broader social and physical context and the central significance of individual
      goals. In particular, the qualities of home and their potential value in the
      promotion of well-being are discussed. This paper presents a review of recent
      literature, followed by an empirical study of homelessness in London. A sample of
      531 adults was staying in squats, hotels, hostels, and on the streets. Each
      setting was examined in terms of qualities of home and a general level of well
      being. The results suggest that this sample experienced low levels of well-being,
      typical of persons experiencing such upheaval. Furthermore, there may be a
      positive relation between levels of well-being and home-like qualities for some
      homeless settings. The paper concludes that a focus on qualities of home may
      contribute to a broader understanding of health and well-being that values
      individual experience and goals.

PMID- 10939088
TI  - The housing/health relationship: what do we know?
AB  - Research into the relationship between housing and health has frequently been
      narrowly focused, fragmented, and of marginal practical relevance to either
      housing or health policy. From an extensive review of the literature, this paper
      reports on the current state of knowledge about the relationship between housing
      and health. The research falls into four distinct categories: (1) specific
      physical or chemical exposures; (2) specific biological exposures; (3) physical
      characteristics of the house; and (4) social, economic, and cultural
      characteristics of housing. Much of the general literature on the effects of
      housing on health cites previous studies and then proceeds to advocate housing
      policies and strategies that are aimed at improving population health. Studies
      providing original data on the relationship, which is the vast majority of the
      literature, focus on very specific physical, chemical, and biological exposures
      with a known or suspected effect on health within the house, or they focus on the
      social, economic, and cultural characteristics of the house. The mechanisms
      through which specific aspects of housing affect health are extremely
      complicated, but they do exist. Researchers have made a great deal of progress in
      clarifying some of these mechanisms. A large gap still exists in our knowledge
      about the links and pathways between housing, socio-economic status and health
      status.

PMID- 10939090
TI  - Health begins at home: the housing-health interface for older people.
AB  - Housing issues are of fundamental importance to the health and independence of
      older people in Britain, but this concept is not reflected in planning for
      health, housing, or community care. An analysis of community care plans and
      public health reports reflects how little attention the majority give either to
      the importance of housing or to the potential of primary care as a means of
      information exchange between older people and planning processes. Interviews with
      practitioners and policy makers in four cities, combined with a review of the
      considerable literature on planning and joint planning in the health and social
      services, helped to identify the problems in achieving more integrated systems.
      Structural blockages as fundamental as the definitions of 'health' and 'housing',
      the attitude of society to manual work, the hidden nature of the problems of
      older people, and the failure of planning to categorize according to the level of
      need are identified and summarized in a chart showing how these factors are
      linked and self-reinforcing. The article concludes with a vision of how things
      might work more effectively without requiring unrealistic changes. The authors
      offer a challenge to planners and joint commissioners to gather different kinds
      of information on need; to have long-term, as well as short-term, strategies; to
      think broadly across categories of issue; and to be prepared to invest money in
      new ways. Most significantly, by redefining the role of the Director of Public
      Health, we identify a focal point at which the responsibility and authority for
      coordinating, championing, and review could lie.

PMID- 10939091
TI  - Informing environmental health policy in urban areas: the HEADLAMP approach.
AB  - Urban areas represent complex environments in which to protect health. Accurate
      and highly resolved information is thus a prerequisite for effective
      environmental health policy. The HEADLAMP approach is designed to improve
      decision-making by providing indicators, based on sound science, to all relevant
      stakeholders, in an appropriate and usable form. The approach comprises three
      linked stages: categorization of the issues to be addressed, construction of
      relevant indicators, and policy formulation and implementation. Nevertheless, the
      application of this approach faces many challenges. The environment-health chain
      is both lengthy and complex, so that a wide range of indicators is needed from
      different points in this chain. The DPSEEA framework provides a useful, though
      limited, structure to help define and organize these indicators. This complexity
      also means that the indicators have to be linked, so that problems can be tracked
      from cause to effect and the effectiveness of actions at different points in the
      DPSEEA chain can be evaluated. Indicators also have to be designed in ways
      reflecting the spatial and temporal complexity of urban areas--namely, the rapid
      rates of change in urban environments and the marked spatial variations in
      environmental and sociodemographic conditions. Effective methods of participation
      are equally essential if the indicators are to represent the concerns of the
      stakeholders involved, and if decisions are to be made on a collective basis.
      Good indicators thus must be designed to fit many different and varying purposes.
      The challenge is to devise indicators that serve these purposes by representing
      the intricacies that are inherent in urban areas, rather than by hiding that
      complexity.

PMID- 10939092
TI  - Exploring decision-making for environmental health services: perspectives from
      four cities.
AB  - Increasing resources are being allocated to environmental health monitoring,
      especially for developing methods and collecting data to construct environmental
      health indicators (EHIs). Yet, little research has focused on understanding how
      communities and service providers make decisions with regard to environmental
      health priorities and the role of indicators in this process. This paper presents
      insights regarding local decision-making that arose from a project to test the
      feasibility of using community-based EHIs to facilitate communication between the
      providers and the recipients of environmental services in four developing-country
      cities. The results of the study indicate that decision-making for environmental
      health services is complex and iterative rather than rational and linear.
      Contextual and process factors play an important role. These factors include the
      morale of service providers, the extent of collaboration between service
      agencies, the priorities of different community groups and relations between
      service providers and communities. Scientific information, in the form of EHIs,
      did not appear to be a key element of decision-making in the settings studied. As
      tools, EHIs are unlikely to become part of the decision-making process unless
      they are integrated with local agendas and backed by strong local representation.

PMID- 10939093
TI  - Healthy cities: overview of a WHO international program.
AB  - Health is the outcome of all the factors and activities impinging upon the lives
      of individuals and communities. The last decade has seen an emerging
      understanding within development circles that living conditions are greatly
      affected by local action, by the work of local government, and by community
      groups and organizations. In addressing health and environmental issues and
      making interventions, an integrated approach, based on 'settings', exemplified in
      the Healthy Cities approach, has proved most effective. A Healthy City project
      can involve people and organizations in the programs and activities that are
      needed for better health, and enables a city or neighborhood to mobilize the
      human and financial resources required to address many health and quality of life
      issues. The WHO program involves implementating city projects and networks in all
      regions of the world and serves as a vehicle for many health programs, including
      major disease control initiatives. Healthy City projects allow Ministries of
      Health to develop stronger partnerships with local government organizations (such
      as the Union of Local Authorities and its members, "Local Agenda 21" initiatives,
      and others). One focus for the program is the development of 'multi-'multi-city
      action plans' for major global priority issues, including AIDS, sanitation,
      women's health, and violence, to ensure that major public health programs are
      strengthened by wider community participation. It is recognized that city
      networking--at national, regional, and international levels--now must be better
      exploited by individual cities and municipalities to solve local health problems.

PMID- 10939094
TI  - Communities defining environmental health: examples from the Colorado (U.S.A.)
      Healthy Communities Initiative.
AB  - Communities are increasingly defining 'health' for themselves, then becoming the
      main actors in actions to improve their health and well being. These community
      members work from a broad and inclusive definition of 'health' that often
      incorporates environmental health as a key aspect. They also assume an
      ecological, or systems, viewpoint that integrates many aspects of the community
      that affect health and well being, including housing, health, economy, education,
      transportation, youth and family issues, as well as health and illness care. This
      paper describes a program that involves 28 large and small, urban and rural
      communities in the United States state of Colorado that undertook this type of
      community-based health improvement project. The Colorado Healthy Communities
      Initiative (CHCI) was designed to bring together citizens in Colorado to work
      collaboratively to make their communities healthier. This paper describes the
      program's background, including its principles, processes, and participants, then
      focuses on the particular aspects of environmental health that communities
      included in their definitions of a 'healthy community'.

PMID- 10939095
TI  - Food, health, and the urban environment.
AB  - Both the production and the consumption of food should help reduce the risk of
      food-borne and non-communicable disease and prevent micro-nutrient deficiency.
      That a safe healthy diet can also be environmentally sound is a bonus. Growing
      foods that promote health in an environment near to consumers can contribute to
      reduced fuel consumption, pollution, transport and packaging costs, and can
      promote biodiversity. This approach can also help create local jobs, improve
      access to food, and promote a sustainable environment. The World Health
      Organization recommends an intake of more than 400 grams of vegetables (in
      addition to potatoes) and fruit every day because this helps prevent non
      communicable diseases and micro-nutrient deficiency. Therefore, urban food and
      nutrition policies are needed to promote health through an integrated approach to
      food, health, and the environment within local communities. The benefits of
      developing urban food and nutrition policies to help increase local food
      production include environmental, social, direct, and indirect economic benefits,
      in addition to the health benefits. These issues are discussed in this paper.

PMID- 10939096
TI  - Urban health: an urban planning perspective.
AB  - Urban planning processes and practices, and their impacts on the health and well
      being of citizens, are numerous and take many forms. Creating living urban
      environments that are conducive to health and well being requires an integrated
      approach between urban planners and health professionals. This article focuses on
      the almost 100 years of experience of Canada's National Capital Commission (NCC)
      in developing urban plans (policy plans, master plans) for planning and building
      Canada's Capital. To address the continuous growing public interest in
      environmental concerns, the NCC developed in the 1990s an integrated approach
      using a strategic environmental assessment (SEA). This approach could be easily
      transferred to various urban-planning contexts worldwide. This paper aims to
      describe the NCC approach, in order to stimulate discussion on growing
      environmental health concerns and urban planning.

PMID- 10939097
TI  - Why urban health cannot be ignored: the way forward.
AB  - Urban health is an increasingly relevant and challenging field of action for the
      European region, and indeed the whole world. Urban health and action at the local
      level represent a high priority for the European Office of the World Health
      Organization. The success and appeal of the Healthy Cities concept to
      politicians, to professionals, and to community activists has resulted in a
      continuing growth of the movement both within and outside Europe. More than 1200
      cities and towns are now involved in the 26 national Healthy Cities networks and
      several regional networks in Europe. Working directly and closely with a
      relatively small network of selected fully committed cities (over two 5-year
      phases: 1988 to 1992 and 1993 to 1997) has proved to be a valuable tool for
      strategic growth and a source of know-how, legitimacy, and continuous learning.
      No plan or strategy for health can be serious without systematically addressing
      poverty, vulnerability, and access to care. The WHO Healthy Cities programme
      gives emphasis on addressing equity and the social determinants of health through
      explicit political commitment and integrative policy making and planning.

PMID- 10939098
TI  - [Diagnosis of nocturnal respiratory disorders. Review of portable screening
      systems. Analysis and critique of different polysomnographic signals].
AB  - Polysomnography in an attended hospital laboratory setting is the gold standard
      for the diagnosis of sleep-related breathing disorders. However, this method is
      expensive and waiting lists are long. Portable recording devices that can be used
      at home have been recently developed to improve upon the problems of
      polysomnography. We review the recent portable devices validated by
      polysomnography and discuss their precise role in the assessment of sleep-related
      respiratory disorders.

PMID- 10939099
TI  - [Pharyngeal musculature and obstructive sleep apnea syndromes].
AB  - An analysis of the way the pharyngeal musculature modulates the caliber of the
      pharynx is important to better understand and treat obstructive sleep apnea
      syndromes. The caliber of the pharynx at the soft palate depends on the action of
      the tensor veli, the palatoglossus, the palatopharyngeus and the uvula muscles.
      At the ligual level, the action of the genioglossus and the geniohyoideus
      predominate. These different muscle groups contract in co-ordination before the
      diaphragm contracts. Their activity is diminished and disorganized during sleep.
      These muscles appears to have a histological composition adapted to short
      duration intense contractions making them vulnerable to fatigue. In apneic
      patients, these muscles are solicited constantly. Muscular lesions related to
      overwork have been suggested. The histological composition of these muscles is
      modified in apneic patients compared with non-apneic subjects (increased number
      of type IIa fibres), the expression of an adaptive process. The degree of
      adaptation varies depending of the pharyngeal level considered. Similar to their
      reflex stimulation, the response of these pharyngeal muscles to increased
      resistance is probably greatest at the soft palate level. Greater solicitation of
      palatine muscles associated with their greater vulnerability to fatigue could
      explain why obstruction is particularly important at this level. A study of the
      mechanical and histological properties of the pharyngeal musculature is required
      for a better understanding of the occlusive mechanisms of the upper airways and
      must be undertaken before initiating therapeutic stimulation of these muscles.

PMID- 10939100
TI  - [Physiopathology of sleep respiratory obstruction anomalies. Experimental methods
      and practical applications].
AB  - Recent progress in the physiology of the upper airways has led to significant
      advances in evaluating the dynamics of upper airway occlusion during sleep.
      Measuring the collapsibility of the upper airways and localizing the site of
      obstruction should theoretically lead to efficacious non-mechanical treatment and
      enable selection of patients susceptible of benefiting from surgical procedures.
      From a diagnostic point of view, fluctuations in the nasal pressure curve appear
      to give more precise information on ventilatory changes and their association
      with disrupted sleep pattern than conventional parameters such as thermistance
      signals or induction plethysmography. Again, from a pathophysiological point of
      view, little is known about the role or tissue inflammation and repeated upper
      airway trauma in the transition from simple snoring to sleep apnea syndrome.
      Current studies lead to the conclusion that the dilatroy muscles of the upper
      airways in the apneic subject are the target for adaptive trophic,
      immunohistochemical and metabolic phenomena in response to stimulation comparable
      to training against resistance. Although there is no evidence that sleep affects
      neuromuscular activity in apneic subjects, the disappearance of compensatory
      hyperactivity on awakening and the reduction of muscle contraction efficacy
      (transmission of the dilatory force to soft tissues) observed in patients may
      explain the greater instability of the upper airways characteristic of sleep
      apnea syndrome.

PMID- 10939101
TI  - [Heart failure and sleep respiratory disorders. Prevalence, physiopathology and
      treatment].
AB  - Cheyne-Stokes respiration occurs during sleep in 40-45% of patients with NYHA
      class III and IV heart failure. Such patients experience repeated episodes of
      progressively diminishing ventilation associated with desaturation followed by
      periods of increasing-amplitude ventilation. The mechanism appears to be related
      to hyperventilation leading to hypocapnia which occurs near a critical threshold
      of apnea during sleep stages I and stage II and interrupts central ventilatory
      control. The total duration of the periodic respiration cycle would depend on the
      increased circulation time subsequent to lowered cardiac output. Brief periods of
      waking provoked by Cheyne-Stokes respiration, accentuating sympathetic nervous
      system activity, are an unfavorable prognostic factor in heart failure.
      Activation of the sympathetic system may be corrected by CPAP although the long
      term effect on heart failure remains controversial. Other treatments, such as
      oxygen therapy or theophylline, combined with optimized treatment of heart
      failure, have been proposed.

PMID- 10939102
TI  - [A difficult baptism. Or does the upper airway resistance syndrome exist?].

PMID- 10939103
TI  - [The upper airway high resistance (or abnormal resistance) syndrome].

PMID- 10939104
TI  - [Autonomic nervous system and sleep apnea syndromes].
AB  - Understanding of the pathophysiology of obstructive sleep apnoea, a common yet
      relatively newly recognised condition, has advanced rapidly in recent years. This
      condition produces major acute haemodynamic changes and causal relationships with
      arterial hypertension and cardiovascular morbidity have been proposed. The role
      that the autonomic nervous system plays in mediating these cardiovascular changes
      has been the focus of intensive research activity and the development of new
      techniques in physiological monitoring, such as spectral analysis of heart rate
      variability, Finapres blood pressure monitoring, measurement of muscle
      sympathetic nerve activity, radionuclide tests and animal models of obstructive
      sleep apnoea have substantially increased the knowledge base. The acute
      haemodynamic changes are associated with high levels of sympathetic discharge and
      with fluctuating parasympathetic activity. There are also chronic changes in
      baroreceptor and chemoreceptor reflexes associated with an increase in baseline
      daytime sympathetic activity and abnormal vagal reflex responses to voluntary
      respiratory maneuvers. These acute autonomic changes appear to be provoked by a
      combination of stimuli triggered by hypoxaemia, upper airway responses,
      ventilatory changes and arousal. The mechanisms of the chronic autonomic changes
      are less clear; it is likely that recurrent hypoxaemia is important, but the
      roles of recurrent ventilatory stress and arousal are not clear. Normalising
      respiration with CPAP therapy prevents the acute cardiovascular changes and
      reduces the acute sympathetic over-activity, and in compliant patients, restores
      abnormal vagal responses to normal and reduces excess chronic sympathetic
      activity. Whether or not this produces a reduction in long term cardiovascular
      morbidity is not established.

PMID- 10939106
TI  - [Auto-controlled continuous positive pressure in the titration and treatment of
      obstruction sleep disorders].
AB  - Self-adjusted Continuous Positive Airway Pressure or autoCPAP machines have been
      engineered to automatically adjust the pressure to maintain the upper airway
      patency. They can be used for titration or long-term home therapy. They have been
      developed to improve efficiency and compliance of CPAP treatment and the cost
      effectiveness of titration and also to decrease the long waiting lists for manual
      titration. For the treatment, it is believed, but not demonstrated, that
      compliance may be increased by lowering the optimal pressure. Most machines are
      piloted by an algorithm based on detection of various combination of respiratory
      events such as apnoeas, hypopnoeas, snoring, inspiratory flow limitation or
      impedance. Several short-term studies have shown that autoCPAP reduces the
      indices of respiratory events and microarousals. In general, optimal CPAP
      determined automatically are identical or lower than evaluated manually by
      experienced technicians. However, the long-term benefits of auto-CPAP on
      compliance have not been determined and require further controlled clinical
      studies taking account not only compliance, but also sleep quality, quality of
      life, alertness and cognition for each autoCPAP. The cost-effectiveness of auto
      titration versus conventional titration remains also to be established.

PMID- 10939105
TI  - [Mandibular advancement orthoses used in the treatment of obstructive sleep apnea
      syndrome].
AB  - Mandibular advancement devices represent a therapeutic option for obstructive
      sleep apnea syndrome (OSAS). Clinical improvement has been proven in the
      different available studies, mainly on nocturnal respiratory events and quality
      of sleep. Less snoring have been noted by bed partners and objective studies have
      demonstrated decrease in snoring frequency and intensity. The effect of these
      ortheses on upper airways resistance syndrome is not yet well documented. The
      significant clinical improvement is secondary to the decrease in the occurrence
      of apneas and hypopneas. Polysomnographic improvement criteria with an apnea
      hypopnea index less than 10 per hour has been noted in certain cases. Although no
      improvement or even worsening was noted in other cases. Sleep architecture has
      also changed in these patients, with a decrease in the time spent in stages 1 and
      2, and an increase in the time spent in stages 3 and 4 and rapid eye movement
      sleep. Micro-arousals are also decreased in number certainly with the decrease in
      the occurrence of respiratory events. Somnolence and loss of attention are
      improved; these have been evaluated subjectively or by a well known and approved
      somnolence scale. In some cases a test for vigilance was done.

PMID- 10939107
TI  - [Titration of the level of effective positive pressure in the treatment of
      obstructive sleep apnea syndromes with continuous positive pressure].
AB  - The efficacy of continuous airway positive pressure ventilation with a nasal mask
      mainly depends on the appropriateness of the effective positive pressure level.
      Conventionally, this level is determined from polysomnographic recordings using
      progressively increasing pressure levels to determine, the point where episodes
      of apnea, hypopnea and snoring regress in all sleep phases and in all body
      positions. Since the first description of this method, many other titration
      methods have been proposed. Some use sophisticated signals such as the analysis
      of respiratory exertion level or limitation of inspiratory flow to provide a more
      precise titration which is particularly useful in cases where the classical
      titration method is insufficiently effective. Inversely, simplified methods have
      been examined from an economic point of view. These methods do not require the
      presence of a technician in a specialized laboratory where the waiting list for
      diagnostic tests is often long. Recordings during naps or short nights have been
      proposed for the more severe cases. Likewise titrations during simple polygraphy
      recordings or with an autoCPAP device have been shown to be effective in one
      night laboratory recordings. Much work remains to be done to determine the
      effectiveness of these methods when used in the patient's home as well the long
      term effects.

PMID- 10939108
TI  - [Classification of muscle cells].
AB  - Muscle cells, including smooth muscle cells, cardiac muscle fibers and skeletal
      muscle fibers, are specialized for generation of movement and force in a specific
      direction. Smooth muscle cells are mononucleate cells, isolated or grouped in
      layers in various tissues, or rarely forming individualized muscles. Smooth
      muscle cell contraction is slow and depends on the autonomic nervous system.
      Cardiac muscle cells are mononucleate striated cells, with fast, rhythmic,
      spontaneous contractions. Skeletal muscle fibers are multinucleate cells at the
      origin of voluntary movements. According to morphological and functional
      criteria, skeletal muscle fibers are classified as type I fibers (slow-twitch
      oxidative), type IIA fibers (fast-twitch oxidative glycolytic) or type IIB fibers
      (fast-twitch glycolytic).

PMID- 10939109
TI  - [Cellular mechanisms of smooth muscle contraction].
AB  - Myosin is an ATPase, able to form filaments with actin, thus initiating smooth
      muscle contraction (conversion of chemical energy into mechanical energy). Myosin
      activity is regulated by cytosolic calcium, via a calcium-calmodulin-MLCK
      dependent phosphorylation. Extrusion of cytosolic calcium via calcium pumps (in
      the plasma membrane and sarcoplasmic reticulum) and via a sodium-calcium exchange
      allow smooth muscle cells to maintain their resting state. Constrictor agonists
      (hormones, neurotransmitters or drugs) act at membrane receptors inducing: (i) a
      fast and transient calcium mobilization from the sarcoplasmic reticulum, via
      phospholipase C (PLC) stimulation and inositol triphosphate (IP3) production or
      via a "calcium-induced calcium release" mechanism and opening of calcium channels
      in the sarcoplasmic reticulum and (ii) a slow and maintained mobilization of
      extracellular calcium, via the opening of voltage-dependent calcium channels in
      plasma membranes. Smooth muscle relaxation is ensured by a phosphatase which
      hydrolyzes phosphorylated myosin and decreases the calcium sensitivity of the
      contractile apparatus. Calcium signal is regulated at that level by: (i) protein
      kinase C, tyrosine kinase and arachidonic acid which inhibit phosphatase activity
      and (ii) cyclic AMP (cAMP) and cyclic GMP (cGMP) which enhance phosphatase
      activity. A second regulatory site is situated at the level of the non
      contractile calcium compartment, which buffers signal transduction and where cGMP
      and/or cAMP enhance calcium extrusion mechanisms.

PMID- 10939110
TI  - [In vitro techniques for the study of muscle contractility].
AB  - Functional studies of bronchial smooth muscle contractility, particularly in
      humans, are now well standardized regarding to tissues collection, tension
      setting and results expression. This type of model is usually considered as
      simple for analysis of pharmacological interactions between ligands and
      receptors. In fact, the multiplicity of cell types implicated in the bronchial
      response makes of isolated bronchi preparation a complex model. Examples are
      given with studies on endothelin or tachykinins. Inflammation and bronchial
      hyperresponsiveness models were proposed. Models of passive sensitization or
      pretreatment with cytokines are described. Functional studies of contractility
      are included in larger investigations including the analysis of the associated
      biochemical and electrical phenomenon.

PMID- 10939111
TI  - [Control of bronchial contractility, regulation of receptor activity and
      expression].
AB  - Heptahelical receptors mediate contractile and relaxant responses of bronchial
      smooth muscle cells to mediators and drugs. The activity of these receptors is
      constitutively regulated through the equilibrium between their inactive
      conformation R and their active conformation R*, coupled to G proteins. This
      equilibrium is shifted to R* by agonists, with a relaxant response to beta
      adrenergic agonists and a contractile response to muscarinic agonists. In
      contrast, inverse agonists shift this equilibrium to R with, for instance, a
      putative relaxant response to muscarinic inverse agonists. The expression of
      heptahelical receptors at the plasma membrane correspond to the equilibrium
      between the endocytosis of membrane receptors and the synthesis of receptor mRNA
      and protein. Endocytosis is activated by agonists and decreased by inverse
      agonists. The transcriptional regulation of heptahelical receptors in bronchial
      smooth muscle cells is tightly controlled by pro-inflammatory cytokines. The
      variety of the involved control pathways might explain the spasmogen-selective
      hyperresponsiveness, allowing a reappraisal of the dogma of non selective
      bronchial hyperresponsiveness in asthma.

PMID- 10939112
TI  - [Special characteristics of bronchial smooth muscle cells].
AB  - Airway smooth muscle is one of the main effectors of bronchial reactivity. Our
      understanding of the cellular mechanisms involved in the contraction of this
      muscle has advanced in the recent past since isolated cells in culture can now be
      studied. Extracellular messengers (neurotransmitters and mediators) as well as
      their specific membrane receptors have been analyzed in some details. Membrane
      transduction of extracellular messengers brings about the formation (or the
      increase in the concentration) of the intracellular second messenger which, in
      airway smooth muscle, is cytosolic calcium (Ca2+i) via activation of calcium
      channels which depend on surface membrane potential changes (electromechanical
      coupling) on one hand and mainly via mechanisms independent of surface membrane
      potential changes, the so called--pharmacomechanical coupling--which involves
      membrane phosphoinositide metabolism. Changes in Ca2+i activate contractile
      proteins leading the muscle to shorten and to develop force via several
      controlled steps such as phosphorylation of myosin or changes in the sensitivity
      to Ca2+ of the contractile elements. Information about the cellular physiology
      and pathophysiology of this muscle is of value to design new drugs for the
      treatment of bronchoconstriction.

PMID- 10939113
TI  - [Biomechanics and bio-energetics of smooth muscle contraction. Relation to
      bronchial hyperreactivity].
AB  - Mechanical studies of isolated muscle and analysis of molecular actomyosin
      interactions have improved our understanding of the pathophysiology of airway
      smooth muscle. Mechanical properties of airway smooth muscle are similar to those
      of other smooth muscles. Airway smooth muscle exhibits spontaneous intrinsic tone
      and its maximum shortening velocity (Vmax) is 10-30 fold lower than in striated
      muscle. Smooth muscle myosin generates step size and elementary force per
      crossbridge interaction approximately similar to those of skeletal muscle myosin.
      Special slow cycling crossbridges, termed latch-bridges, have been attributed to
      myosin light chain dephosphorylation. From a mechanical point of view, it has
      been shown that airway hyperresponsiveness is characterized by an increased Vmax
      and an increased shortening capacity, with no significant change in the force
      generating capacity.

PMID- 10939114
TI  - [The role of inflammation in the modulation of bronchial hyperreactivity.
      Potential therapeutic applications].
AB  - The exact functional contribution of the various inflammatory cells, mediators,
      cytokines and growth factors present in asthmatic airways to bronchial
      hyperresponsiveness remains to be fully established. Gene knock-out in vivo
      animal models can provide valuable information in this respect. Obviously, the
      closer the animal models mimic human disease, the more relevant this information
      will be. This constitutes the major limitation of murine asthma models to date.
      Key characteristics of asthma include from a morphological point of view, signs
      of an acute allergic airway inflammation in combination with airway remodeling,
      and from a functional point of view, hypersensitivity and hyperreactivity of the
      airways. Neither of these two main characteristics are properly mimicked in
      currently developed animal models. The degree of airway hyperresponsiveness
      obtained in these models is generally small, when compared to the degree of
      hyperresponsiveness observed in asthmatics. This probably relates at least in
      part, to the differences in airway inflammation, as in most of the murine models,
      only acute inflammatory changes are induced without chronic structural changes
      that might affect responsiveness to a large degree. The shortcomings of these
      models notwithstanding, gene knock-out models of asthma have revealed some
      interesting observations. The majority of these models has evaluated the exact
      functional role of TH2 cells, interleukin-4, interleukin-5 and IgE in the
      pathogenesis of allergic airway inflammation and airway hyperresponsiveness.
      Overall, it can be argued that neither the IgE/mast cell axis, nor the IL
      5/eosinophil axis, are the cause of airway hyperresponsiveness, but that the T
      cell in its own right is the main determining factor in establishing the degree
      of bronchial hyperresponsiveness.

PMID- 10939115
TI  - [Role of bronchial smooth muscle in inflammation].
AB  - We now have to consider the airway smooth muscle as an actor of the bronchial
      inflammation in asthma. In addition to its bronchoconstricting role in response
      to mediators secreted by the adjacent cells and tissues, that may be considered
      as to be passive regarding the airway inflammation, the airway smooth muscle may
      now be considered as pro-inflammatory, since it has the potential of synthesizing
      and secreting a variety of chemokines and growth factors that will favor cell
      proliferation, and attraction of inflammatory cells. The airway smooth muscle may
      modify its phenotype from a contractile to a secretory or a proliferative
      phenotype. These differentiation states of the bronchial smooth muscle may be
      studied experimentally by culturing the airway smooth muscle. The demonstration
      of the occurrence and/or coexistence of such differentiation states in vivo will
      help understand the exact role of the bronchial smooth muscle in the airway
      inflammation in asthma.

PMID- 10939116
TI  - [Genetic polymorphism and asthma].
AB  - Several mutations have been found in genes encoding for proteins implied in the
      pathophysiology or the treatment of asthma. Until now, no causal role could not
      be highlighted. The mutations were mainly studied on gene coding for the beta 2
      adrenergic receptor being able to be associated with modifications of the
      phenotype of asthma or even to modifications of response to some beta 2 agonists.
      Certain polymorphisms of the beta 2 adrenoceptor are associated with
      polymorphisms in genes coding for peptides controlling the expression of the beta
      2 adrenoceptors. The interpretation of the effects observed must take into
      account this linkage disequilibrium.

PMID- 10939117
TI  - [Special characteristics of the diaphragm muscle cell].
AB  - The diaphragm is the main inspiratory muscle, accounting for more than 50% of the
      tidal volume during quiet breathing. It works continuously, contracting
      rhythmically and generally at a low intensity. In this respect, it is close to
      the myocardium, being the only vital skeletal muscle. From a general point of
      view, functional and biochemical characteristics of the diaphragm are similar to
      those of other skeletal muscles with a similar fiber type composition. However,
      the diaphragm presents some specificities allowing a high supply of metabolic
      substrates. This could serve to preserve contractile function in different
      physiological and physiopathological situations. Such specificities concern
      muscular vascularization, the microvascular network and the content of
      mitochondria and myoglobin. These characteristics are detailed and compared to
      those of other striated muscles.

PMID- 10939118
TI  - [Clinical relevance of myosin isoforms in the diaphragm].
AB  - The diaphragm as a striated muscle is characterized by the repetition of a single
      element arranged in series: the sarcomere containing two kinds of myofilaments: a
      thick one constituted by the myosin, and a thin one primarily composed of actin.
      The myosin molecule consists of two heads where two myosin heavy chains (MHC) are
      fixed, a flexible hinge with two light (MLC) chains, and long rod-shaped tails.
      The diaphragm contains 4 MHC isoforms (MHC-slow, MHC-2A, MHC-2B, MHC-2X) and 6
      MLC isoforms (MLC-1f, MLC-3f, MLC-1sa, MLC-1sb, MLC-2f, MLC-2s/v). In humans, the
      diaphragm contains mainly fibers expressing the isoforms MHC-slow, MHC-2A, and
      MLC-2f, MLC-2s et MLC-1f. For the mechanical properties of the different
      isoforms, there is a gradient from the MHC-slow to the MHC-2A, MHC-2B and MHC
      2X/2B. According to the circumstances, the diaphragm will adapt towards a slow
      profile (COPD, cardiac failure and in animals: Duchenne muscular dystrophy,
      denervation-1 week, age-female, corticosteroids, chronic stimulation), or a fast
      profile (in animals: chronic hypoxia, denervation-2 weeks, age-males) or a more
      oxidative profile (in animals: cachexia, obesity). The reasons why the diaphragm
      adapts towards a slower or a faster muscle are not known. In fact, for a given
      pathological situation, several factors are able to influence the fiber
      composition of the diaphragm. Therefore, the net result of the influence of these
      different factors in terms of MHC and MLC diaphragm adaptation is difficult to
      predict.

PMID- 10939119
TI  - [Ontogeny of respiratory muscle control. Evidence from the amphibian model].
AB  - The mechanisms which control the cyclic contraction of the respiratory muscles
      remain uncertain. The ontogenic approach is attractive but difficult in mammals.
      The bullfrog larva, the tadpole, provides a model easier to study as its
      brainstem can be isolated in vitro. The tadpole undergoes a development from
      exclusive gill ventilation to bimodal breathing and, eventually, to exclusive
      lung ventilation. During the metamorphic stages, lung ventilation is not
      dependent upon inhibitory mechanisms, suggesting that pacemaker neurones may
      possibly drive the lung rhythm. This is not the case for the gill ventilation.
      However, inhibitory mechanisms are probably involved in the shape of the lung
      discharge in the adult frog. During the development of the tadpole, the regions
      of the brainstem responsible for the lung rhythm migrate rostrally, the
      sensitivity to hypoxia shifts from gill ventilation to lung ventilation and the
      sensitivity to hypercapnia develops with the lung ventilation. The ontogenic
      particularities of tadpole breathing and the study of its isolated brainstem
      provide a unique model for the investigation of the ventilatory rhythm
      generation.

PMID- 10939120
TI  - [Clinical investigation of diaphragmatic function. Relationships with the biology
      of muscle].
AB  - Diaphragmatic strength, which can be roughly estimated by non invasive techniques
      such as maximal inspiratory pressure or sniff nasal pressure, is specifically
      assessed by the measurement of transdiaphragmatic pressure during electric or
      magnetic phrenic nerve stimulation. However, muscle endurance is probably a more
      relevant parameter in pulmonary disease. Recent progress in the field of
      diaphragm biology were mainly obtained in animal models. Data in human disease
      are currently restricted to COPD and steroid induced myopathy. In COPD patients,
      recent studies demonstrated significant adaptations of diaphragm fibers
      susceptible to counterbalance the mechanical disadvantage due to hyperinflation.
      These changes include an increased proportion of fatigue resistant type I fibers,
      a decrease in sarcomere length and an increase in mitochondrial density.
      Regarding corticosteroid induced myopathy, numerous experimental studies are
      available whereas data are scarce in human disease. Respiratory corticosteroid
      myopathy is characterized by markedly decreased strength and endurance of
      inspiratory muscles. Histologic data obtained by quadriceps biopsies in COPD
      patients demonstrated diffuse fiber atrophy, increased variation in diameter of
      fibers and diffuse necrotic fibers. Recent data in rats suggest that decreased
      IGF expression induced by corticosteroids might contribute to diaphragmatic
      changes.

PMID- 10939121
TI  - [Clinical and molecular epidemiology of lymphangioleiomyomatosis and pulmonary
      pathology in tuberous sclerosis].
AB  - Pulmonary lymphangioleiomyomatosis is characterized by a proliferation of
      abnormal smooth muscle cells in peribronchial, perivascular and perilymphatic
      areas leading to cystic destruction of the pulmonary parenchyma. Recent clinical
      series of LAM have been helpful in better describing the various clinical and
      radiological forms of the disease, although our understanding of the
      pathophysiological mechanisms of LAM remains very limited. Significant progress
      has been noted in recent years with the discovery of probable antigenic and
      genetic similarities between pulmonary lymphangioleiomyomatosis, Bourneville
      tuberous sclerosis and renal angiomyolipoma. The proliferating cells in LAM share
      with normal smooth muscle cells their reactivity with desmine, vimentin and actin
      but certain are different by their reactivity with the monoclonal antibody HMB45,
      a common antigen marker of melanocyte differentiation cells, clear-cell lung
      carcinomas or renal angiomyolipomas. A loss heterozygosity in the region of the
      TSC2 gene in renal angiomyolipomas has been demonstrated in association with
      pulmonary lymphangioleiomyomatosis. The TSC2 gene is particularly implicated in
      the pathogenesis of Bourneville tuberous sclerosis.

PMID- 10939123
TI  - Case of the season. Primary central nervous system B-cell non-Hodgkin's lymphoma
      involving the brain.

PMID- 10939122
TI  - [Regulation of the differentiation and proliferation of smooth muscle cells by
      the sex hormones].
AB  - Steroids effects are mediated by their receptors. These proteins define the large
      family of steroid hormone receptors, characterized by the presence of 3
      functional domains: a transactivation domain, a DNA-binding domain and a ligand
      binding domain. Receptor activation induces the modulation of transcription of
      specific genes, and as a consequence, the modulation of production of specific
      proteins. Sex steroid receptors are located in the nucleus. This nuclear
      localization is in fact a dynamic situation, resulting from a continuous
      shuttling of the receptor between the cytoplasm and the nucleus. The recent
      discovery that an additional estrogen receptor is present in various tissues has
      advanced our understanding of the mechanism underlying estrogen signalling. Non
      genomic effects of steroids have also been described. Sex steroids inhibit
      proliferation of smooth muscle cells. On the contrary, they stimulate
      proliferation of tumoral muscle cells. The mechanisms of sex steroid effects on
      cellular proliferation are complex, and may involve transcriptional or non
      transcriptional phenomena.

PMID- 10939124
TI  - Magnetic resonance imaging of the rotator cuff.

PMID- 10939125
TI  - Magnetic resonance imaging of the knee menisci.
AB  - MRI remains the most useful noninvasive test for diagnosis of meniscal tears.
      Knowledge of normal anatomy and familiarity with patterns of meniscal tears are
      prerequisites when interpreting MRI studies of the knee. Radiologists should pay
      close attention to technical factors, normal variants, and associated
      abnormalities to maintain high diagnostic accuracy. Details of meniscal tears
      should be described as to best aid in orthopedic decision-making.

PMID- 10939126
TI  - Current concepts in magnetic resonance imaging of the adult hip and pelvis.
AB  - MRI is the diagnostic imaging modality of choice for most disorders of the hip
      and pelvis in the setting of nondiagnostic plain radiographs. Quality images of
      the entire pelvis with high-resolution images of the affected hip are
      recommended. Intravenous gadolinium is administered in cases of suspected soft
      tissue or bone infection. MR arthrography enables assessment of the joint space
      and the acetabular labrum. With MRI, the radiologist has the ability to stage
      pathological conditions of the hip and pelvis in such a way as to determine
      prognosis and influence therapeutic decisions.

PMID- 10939127
TI  - Magnetic resonance imaging of articular cartilage.

PMID- 10939128
TI  - Magnetic resonance imaging of the knee ligaments.

PMID- 10939129
TI  - Magnetic resonance imaging of the glenoid labrum.

PMID- 10939130
TI  - Magnetic resonance imaging of the hand and wrist.

PMID- 10939131
TI  - Magnetic resonance imaging in primary bone tumors.
AB  - MRI plays a major role in the evaluation and treatment planning of bone tumors.
      It should be used following plain films and before biopsy. The MR appearance of
      most tumors is nonspecific; however, the entire extent of the tumor and its
      relationship to adjacent structures can be determined at MRI providing a road map
      for the surgeon. The role of dynamic enhancement is evolving and has not yet been
      determined.

PMID- 10939132
TI  - Magnetic resonance imaging of the foot and ankle.

PMID- 10939133
TI  - Social inequality and environmentally-related diseases in Germany: review of
      empirical results.
AB  - A literature search was conducted aiming at all empirical studies from Germany
      till mid 1997 containing data on the association between environmentally-related
      diseases and the socio-economic status (education, occupation, income, social
      class) and/or on the association between the exposure to harmful substances and
      the socio-economic status. With respect to the exposures, a clear picture becomes
      visible: the concentration of harmful substances in the ambient air as well as
      indoors is considerably higher with regard to the lower social class as compared
      with the higher social class. This applies to children as well as to adults and
      to West Germany as well as to East Germany. However, with respect to
      environmentally-related diseases, no such clear picture becomes visible. For
      example, several studies indicate that allergies, atopic eczema and croup occur
      less frequently in the lower social class than in the higher social class.
      Malignant tumours (lung cancer, kidney cancer or bladder cancer), however, seem
      to occur more frequently in the lower social class than in the higher social
      class. Environmental-epidemiological studies should increasingly integrate socio
      epidemiological study approaches and explicitly present their results.

PMID- 10939134
TI  - [Ultraviolet exposure in childhood and in adulthood: which life period modifies
      the risk of melanoma more substantially?].
AB  - The paper is devoted to the analysis of the relationship between the frequency of
      sunburns in childhood and adulthood, respectively, and the occurrence of
      malignant melanoma of the skin. The analysis is based on case-control data of 603
      melanoma cases and 627 population controls from 11 participating centers in seven
      European countries. The results confirm the increase in melanoma risk for an
      increasing number of sunburns during childhood and adulthood in the same
      magnitude of risk elevation. The maximum OR for the highest exposure category of
      more than five sunburns was during the childhood 2.0 (95%-CI: 1.2-3.5) and during
      the adulthood 2.1 (95%-CI: 1.4-3.3), respectively. The analysis of the joint
      effects of sunburns during child- and adulthood on melanoma development
      corroborated these findings. In this joint analysis an OR of 2.1 (95%-CI: 1.3
      3.5) quantifies the melanoma risk of those with three or more sunburns during
      child- and adulthood, respectively, compared to those without any sunburns during
      these periods. The study does therefore provide no supporting evidence for the
      presence of "critical period" during childhood in which a higher melanoma risk
      due to sunburns has been suggested by other studies.

PMID- 10939135
TI  - [Hip joint operations in routine patient management--determinants of quality of
      life].
AB  - The study was conducted in co-operation with a German sickness fund to identify
      determinants of health related quality of life (HRQL) after hip surgery in
      routine health care. In 9/97 all beneficiaries (age 40-75 years), which were
      treated in hospital for osteoarthrosis (n = 1352), were sent a questionnaire on
      average 5.2 months (t1), postoperatively. The standardized questionnaire
      contained a.o. items about pre- and postoperative subjective assessment of
      disease specific symptoms (Lequesne-Index), complications, comorbidity, health
      related quality of life (SF-36). The response rate at t1 was 67.8%. Patients with
      hip surgery (n = 390) were sent a second questionnaire 17.2 months (t2)
      postoperatively. At t2 data from 293 patients were available for analysis.
      Patients (57.6% male) were on average 61 years of age and 61.2% reported no co
      morbidity. 88.4% received total hip replacement. 30.3% of patients reported at
      least one complication. HRQL in patients after hip surgery is significantly
      impaired in six of the eight SF-36 subscales compared to the German norms at t1
      and t2. From t1 to t2 substantial improvements appear in the SF-36 subscales
      physical functioning, role physical and bodily pain (p < 0.001). Major
      determinants of HRQL are comorbidity (if yes: less improvement) and attendance of
      inpatient rehabilitation (if yes: more improvement). In routine healthcare HRQL
      after hip surgery is determined by patient characteristics and postoperative
      rehabilitation. Inspite of substantial improvements patients did not (yet) reach
      the level of the reference population.

PMID- 10939136
TI  - [A multidimensional questionnaire as a component of preventive geriatric
      assessment: comparison of self-assessment version with the interview version].
AB  - In an earlier study we have shown good internal consistency and test-retest
      reliability of a newly developed German-language instrument in the interviewer
      administered version. The aim of this study was to test the reliability of a self
      administered version compared to the original interviewer-administered version of
      our newly developed German-language instrument. We recruited a group of 50 over
      75-year-old community-dwelling persons in Hamburg, Germany (N = 25) and Berne,
      Switzerland (N = 25). The questionnaire contains items on: self-perceived health,
      chronic conditions, basic and instrumental activities of daily living, urinary
      incontinence, nutrition, recent falls, pain, the social support/network and
      preventive-care measures. In addition, the Functional Status Questionnaire, the
      Physical Activity Scale for the Elderly, the Geriatric Oral Health Assessment
      Index, the Visual Function Questionnaire, the Hearing Handicap Inventory for the
      Elderly and the Geriatric Depression Scale were administered. Cohen's Kappa (self
      administered version compared to the interviewer-administered version) was good
      to excellent (0.69-1.0) with only three exceptions (physical activity kappa =
      0.49, basic activities kappa = 0.54 and oral health kappa = 0.54). For the
      domains activities of daily living, oral health, visual function and depression
      the self-administered version detected significantly more problems than the
      interview. In the future the self-administered version of this assessment
      instrument can be used for various purposes, e.g. (annual) preventive geriatric
      assessment for outpatients and other community-dwelling persons and
      epidemiological studies in older persons.

PMID- 10939137
TI  - [Predictability and rehabilitation of athletic injuries: effects of life style,
      coping ability, and personality].

PMID- 10939139
TI  - [Reproducibility of lumbar spine kinematics in clinical gait analysis].
AB  - The objective measurement of functional lumbopelvical movements enables the
      evaluation of the quantity and quality of movements referring to functional
      disorders in dynamic test-situations. The goal of the present study is the
      determination of the reproducibility of time-continuous movement analysis of the
      pelvic region during walking and the determination of possible errors. The
      movements of the thoracic (Th12), lumbar and sacrum-region (S1) of 17 healthy
      subjects (age: 32.1 +/- 2.3 years) during walking on a treadmill (4.5 km/h) were
      investigated twice in an interval of 24 hours by means of a 3D ultrasonic
      movement analysis system. The ensemble averages of the low-pass filtered and time
      normalized angle-time sequences of all anatomical planes and regions showed high
      test-retest correlations (r > or = 0.92, p < 0.01) except fo the lumbar movement
      in the sagittal plane (r = 0.79, p < 0.01). A paired t-test showed no significant
      differences for the amplitudes of test and retest measurements except for the
      thoracolumbar movement in the sagittal plane (p < .05). The results show that the
      evaluation of lumbar movement patterns can be regarded as admissible and
      desirable for clinical movement analysis. The data can be used as a diagnostic
      tool for the planning and control of therapeutic interventions.

PMID- 10939138
TI  - [Pattern of injuries and prophylaxis in paragliding].
AB  - This study will present trends and recommendations to increase active and passive
      safety in paragliding on the basis of current state-of-the-art equipment and
      typical patterns of injury. This German-Swiss teamwork presents data of 55 male
      and 9 female patients treated after paragliding accidents between 1994 to 1998
      respectively 1996 to 1998. 43.7% of the pilots presented with multiple injuries,
      62.5% suffered spinal fractures and 18.8% pelvic fractures. 28.4% of the injured
      pilots were admitted with injuries of the lower extremities mainly affecting the
      tarsus or the ankle joint. Only three patients with single injuries could be
      treated in an ambulatory setting. 54.0% of the injuries left the patients with
      lasting functional residues and complaints. Main causes of accidents were either
      pilot error in handling the paraglider or general lack of awareness about
      potential risk factors. 46.0% of injuries occurred during landing, 42.9% of
      injuries during the flight and another 11.1% of injuries during starting
      procedures. With noticeable enhanced performance sails of the beginners and
      intermediate level are increasingly popular. Protective helmets and sturdy
      footwear reaching above the ankle joint are indispensable pieces of equipment.
      The use of protective gloves is highly recommended. Back protection devices of
      the new generation provide the best passive prophylaxis for the pilot against
      pelvic and spinal cord injuries. This area hold the most promise for increasing
      safety and reducing risk of injury in future, apart from using beginners and
      intermediate wings. After acquisition of the pilot license performance and
      security training provide the best preparing to master unforeseeable situations.

PMID- 10939140
TI  - [Spine stabilizing muscles in golfers].
AB  - Although golf is perceived as a sport with low risk for injury, majority of golf
      players complain about problems along the spine. One possible reason could be
      poor physical condition. To see if golf players in general show deficits in spine
      stabilizing muscles, twenty-three male golfers without back pain were examined
      with regard to their maximal isometric strength of trunk muscles. They were
      compared with persons of same age and constitution that do no sports. The Golf
      players have highly significant stronger lumbar extensors and show muscular
      dysbalance in lateral flexors and rotators of the spine. Specific training for
      well-balanced strengthening of spine-stabilizing muscles seem to be advisable,
      because muscular dysbalance can contribute to the development of back pain.

PMID- 10939141
TI  - [Pattern of injuries and risk of injury in skateboarding].
AB  - After the first big wave in the late seventies skateboarding is facing a revival
      as a leisure sport nowadays. 63 Skateboarders with a mean age of 18.1 years were
      personally interview with a survey form. 148 injuries with a resulting sport
      break of at least one week were registered. Sprains (36.5%), bruises (24.3%),
      fractures (18.2%) and lacerations of the skin (12.8%) were the most common
      injuries. 86.5% were injuries of the extremities almost equally distributed among
      the upper and lower limbs. Most fractures happened to the upper limbs (81.5%)
      mainly distal of the elbow joint. Sprains were mainly located at the lower limbs
      (70.4%) especially at the ankle joint as the most vulnerable part of the body
      (26.4% of all injuries). 101 injuries (68.2%) were treated by physicians. The
      resulting risk of injury was one injury per athlete and 1000 hours of exposure
      time. A higher acceptance of prophylactic measures could minimize the risk of
      injury. Parallels to inline skating and snowboarding can be shown.

PMID- 10939143
TI  - [Discussions on the approach to the development of German health systems].

PMID- 10939142
TI  - [Osteoid osteoma in the differential diagnosis of knee pain in athletes].
AB  - We report on a 24-year old recreational sportswoman who is suffering on a knee
      pain after taking part in sports involving strength. The diagnosis of an osteoid
      osteoma was established. Diagnostic and therapeutic possibilities are presented.

PMID- 10939144
TI  - [Methodological standards of the evidence-based approach of clinical guidelines
      development in Germany. Consensus between the scientific community, self-governed
      bodies and practice].
AB  - The most appropriate method of clinical guidelines development has been the
      subject of controversial debates in Germany during the last few years. The German
      Guidelines Clearinghouse at the Society for Quality in Medicine (Cologne)
      provided a discussion forum where clinicians, methodologists, the Association of
      the Scientific Medical Societies, and the corporate self-governed bodies (the
      health insurances, physicians' associations, and the hospital associations)
      agreed on the most important methods of an evidence-based approach for guidelines
      development. It was generally agreed that rigorous methodological standards
      should be followed to ensure both the scientific quality and the consensus
      quality in the development or revision of clinical practice guidelines. The
      agreement draws on the following topics: Scientifically valid guidelines: (1) are
      based on a comprehensive and systematic review of the best available evidence,
      (2) derive the recommendations from the best available evidence, and (3)
      demonstrate explicitly how the recommendations are linked to the evidence. The
      quality of consensus is ensured through (1) the participation of all relevant
      stakeholders in the guideline panel and (2) the application of formal consensus
      development methods. This type of an "evidence-based consensus guideline" is
      assumed to possess the highest level of scientific and political legitimacy.

PMID- 10939145
TI  - [Guidelines Clearing House Statement "Hypertension". Summary and recommendations
      for a rational hypertension guideline in Germany].
AB  - BACKGROUND: In order to promote quality of hypertension management in Germany, a
      national hypertension guidelines clearing project was initiated in 1999 by the
      German Guidelines Clearinghouse. OBJECTIVES: To identify and review published
      German- and English language hypertension guidelines. To establish criteria for
      future guideline development and implementation. To familiarize stakeholders in
      Germany with state-of-the-art hypertension guidelines. To identify key topics for
      a future national evidence-based guideline. METHODS: Search procedure, formal
      appraisal: Systematic search using literature databases and English-/German
      language databases, published between 1990 and 1999. Abstract screening of the
      search results according to the inclusion criteria (n = 132 of a total of 548
      hits). Systematic guideline evaluation using checklist with predefined criteria.
      APPRAISAL OF GUIDELINES' CONTENTS: Peer review of guidelines with the following
      inclusion criteria: hypertension--general, German and English language, published
      later than 1994, original or primary guideline or update, issued for nationwide
      use. Peer review was performed by a multidisciplinary focus group of EBM experts
      (primary and secondary care physicians, clinical pharmacologist, clinical
      epidemiologist). None of these was involved in hypertension guideline development
      during the review period. DOCUMENTATION OF CRITICAL APPRAISAL RESULTS: Systematic
      documentation of methodological appraisal and peer review results using a
      structured abstract form. The focus group wrote a final report (clearing report)
      including methodological abstracts for each guideline, essential topics for a
      future German hypertension guideline based on examples from the appraised
      guidelines, comments and recommendations for health care policy markers in
      Germany. RESULTS: 11 out of 132 guidelines were in accordance with the formal
      minimal standard with a wide range range within the following domains:
      "description of the development process", "declaration of authors' independence",
      "explicit link between recommendations and the supporting evidence", "management
      options", "tools for implementation". None of the guidelines identified all the
      key identified by the focus group, such as: (1) definition of hypertension-
      epidemiology--health care problems--intended guideline users/goals, (2) blood
      pressure measurement, (3) medical history and physical examination, (4) case
      finding/screening, (5) indications for referral, (6) risk-stratification, (7)
      diagnostic procedures, (8) therapeutic goals/indications for therapy, (9)
      nonpharmacological measures, (10), pharmacotherapy, (11) follow-up/patient
      education/motivation/compliance, (12) comorbidity, hypertension in
      childhood/elderly, pregnancy, (13) primary prevention, (14) quality
      assurance/quality management, (15) dissemination/implementation, (16) open
      questions/challenges for the future. SUMMARY POINTS: To improve the quality of
      hypertension management in Germany, the expert panel suggested to develop a
      national evidence-based guideline. This should follow internationally agreed
      criteria and procedures. The experts identified and reviewed 11 out of 132
      hypertension, which might make useful contributions for a future German
      Hypertension guideline. The expert group identified 16 key topics for a national
      hypertension guideline.

PMID- 10939146
TI  - [Conception and testing of a regional practice guideline using bronchial asthma
      as an example].
AB  - Frequently, there is a gap between publication and implementation of guidelines
      into clinical practice. To improve adherence with guidelines, experts recommend
      among other things local adaptation of guidelines. The goal of the present study
      was to conceptualize and test such an adaptation in the region of Neckar-Alb in
      Germany by using asthma guidelines as an example. We conceptualized a three-step
      approach for regional guideline adaptation: 1) Compilation of existing national
      and international asthma guidelines by regional experts to develop a draft for
      regional asthma guideline; 2) regional consensus conference to discuss the draft
      with local physicians; 3) modified Delphi procedure using regional physicians as
      "experts" to get consent for the regional asthma guideline. We defined consensus
      as reaching at least a 2/3 consent for each of the statements. As starting point
      for the process of guideline adaptation, the regional experts developed a first
      draft of the regional asthma guideline including 132 recommendations. 60 out of
      500 regional general practitioners (GP), internists and asthma specialists
      participated in the consensus process. After the preparations of the regional
      experts and the regional consensus conference, only four recommendations had to
      be changed considerably during the Delphi procedure to reach the consensus
      criterion. If the recommendations remained unchanged, the whole guideline might
      be disapproved because they were considered to affect the role of GPs by shifting
      responsibilities from GPs to asthma specialists. As the result of the adaptation,
      the first regionally adapted asthma guideline for the Neckar-Alb region fosters
      the principal responsibility of regional GPs in asthma care, thereby surmounting
      resistance for implementation that former specialist-centered guidelines
      provoked. Hence, the new guideline meets the requirements for successfully
      implementing the recommendations into clinical practice.

PMID- 10939147
TI  - [Guidelines for the treatment of adult patients with bronchial asthma in the
      Neckar-Alb region].

PMID- 10939148
TI  - [Previous experiences with the evaluation of guidelines. Disillusionment after an
      enthusiastic start].
AB  - The evaluation of medical guidelines shows that the development and
      implementation of medical guidelines have failed to meet the high expectations
      raised both in Germany and internationally. Especially, the quality of German
      guidelines has been strongly criticized. Since then, several 'guidelines for
      guidelines' were published, and a variety of other measures were taken to define
      quality standards for the development and implementation of guidelines. It is
      expected that the application of these new standards will improve the quality of
      medical guidelines and therefore increase the chances for a more successful
      implementation. Only guidelines with high quality and wide acceptance, which are
      actually applied, will have positive effects on the process and outcome of
      medical care. But guidelines are only one way to improve the quality of medical
      care. The decision about the development and use of new guidelines should be
      based on the careful consideration of possible improvements and disadvantages.

PMID- 10939149
TI  - [Deficits in the treatment of chronic pain (I)].
AB  - Pain management by general practitioners often is inadequate. Guidelines for pain
      management are either not observed or not known at all. Opioids are not
      prescribed adequately. Differential diagnoses influencing the therapeutic regimen
      such as drug-induced headache are not sufficiently known. Monotherapies with
      analgesic drugs are enforced for patients with chronic lower back pain in spite
      of low efficacy. Improving pain management can be difficult for the general
      practitioner having no special knowledges or support from pain specialists.
      However, the general practitioner should remain the patient-coordinator for the
      patient with chronic pain. Networks with general practitioners and specialised
      units in the hospital may offer possibilities for improvement of pain management
      deficits.

PMID- 10939150
TI  - [Bronchial asthma--expectations and concepts of general practitioners].
AB  - Discrepancies between asthma management in general practice and national as well
      as international guidelines and recommendations are currently not fully
      explained. Subjective conceptions, ideas and beliefs are likely to be as
      important as factual knowledge when physicians decide how to treat their
      patients. Our study is part of the European Drug Education Project, an
      international project promoting rational pharmacotherapy in 5 European countries.
      Interviews on asthma and its treatment were conducted with 20 general
      practitioners in Germany, emphasizing beliefs and ideas on the disease and its
      origins as well as treatment goals and options rather than factual knowledge.
      Qualitative analysis was performed using a phenomenographic approach.
      Phenomenography aims at describing "subjective" reality, as it is conceived by
      people to understand learning and reflection processes. Even though most
      physicians know the treatment recommendations for asthma, adherence is variable.
      Reasons can be found in the variability of disease conceptions, often emphasizing
      psychosomatic or patient-centered aspects. The importance of individual treatment
      goals and experience of the doctor-patient relationship in a general practice
      setting is highlighted. Uneasiness concerning specialist recommendations on
      disease management and pharmacotherapy are commonly expressed. There are
      considerable variations in the physicians' conceptions on asthma and its
      management. Understanding these attitudes can provide a rational basis for the
      development of guidelines and implementation strategies corresponding to the
      needs of primary care physicians.

PMID- 10939151
TI  - [Surveys on patient satisfaction in ambulatory care. Practicability, acceptance
      and relevance from the physician's perspective].
AB  - Surveys on patient satisfaction have become an integral part in quality
      management. Adequate survey conduction and appropriate feed back of survey
      results are essential prerequisites for a successful transfer of survey results
      into practice. During the validation of a new instrument to assess patient
      satisfaction in ambulatory care, we assessed the practicability, acceptance and
      relevance of the procedure used in this study (distribution and return of
      questionnaires, preparation of results and comparative feed back) from the
      perspective of the participating physicians (N = 60). Our results confirm, that
      physicians gain a considerable amount of information on quality of care from the
      patient's perspective, provided that results are fed back appropriately. Two
      thirds of the participating physicians (65%) obtained ideas and suggestions for
      quality management and improvement. Most of the ideas were realised at the time
      the physician survey took place. Recommendations for conducting patient surveys
      in ambulatory care and feed back of survey results for participating physicians
      are presented.

PMID- 10939152
TI  - [Quality management in diabetology by the PC software program DIQUAL].
AB  - Today, effective therapies for patients with diabetes mellitus. However, these
      therapeutic strategies are often not or incorrectly applied. Following these
      discrepancies for health care providers, it is mandatory to document the efficacy
      of diabetes treatment. However, it is hard to prove the outcome of diabetes care
      because of unsuitable documentation, missing parameters and different definitions
      of quality indicators. The computer programme DIQUAL was developed to improve the
      diabetes management on the diabetes ward, the diabetes out-patient department and
      for the documentation of outcome quality. DIQUAL is a patient database and offers
      structured data collecting and administration, text processing, referring
      letters, application and list functions, internal and external quality control,
      as well as cohort or cross-section analysis, data export function for nation wide
      data collection, system internal plausibility check and extension modules for
      scientific studies. On the basis of DIQUAL, the first nation wide comparison of
      outcome quality in the routine treatment of type 1 diabetes was possible. In
      1998, we analysed the original data of 1789 patients from 32 district and
      university hospitals on the basis of the therapeutic goals. HbA1C decreased 1.8%
      and the incidence of severe hypoglycaemia was lowered to the half. There was a
      substantial improvement of processes in the health care institutions and the
      quality of information transmission to the general practitioners. This system of
      measurement and improvement of quality is also suitable for other areas in health
      care and medicine.

PMID- 10939153
TI  - [Treatment guidelines--primary and secondary prevention of stroke. From the
      Recommendations on Primary and Secondary Prevention of Stroke of the Medical
      Commission of the German Medical Society, July 1999].

PMID- 10939154
TI  - [Preventive care for early detection of diabetes mellitus complications: a model
      project in Wolfsburg].
AB  - In the city of Wolfsburg, an annual screening to detect diabetic complications
      was introduced. In this model, project internists and general practitioners were
      remunerated for the documentation of diabetic complications. Ophthalmologists
      were remunerated for the documentation of screening for diabetic eye disease. The
      patients received a copy of the results. 1,563 patients (2.57% of 60,800 persons
      insured by the Volkswagen health insurance in the city) received ophthalmologic
      examination. 1,554 patients (2.6%) were examined by internists and general
      practitioners (58 practices). Out of 2,879 eyes examined in no retinopathy was
      detected 80.9%. In 14.1%, mild or moderate retinopathy was observed as well as
      3.3% severe non-proliferative retinopathy and 1.3% proliferative retinopathy. 32
      amputations were documented. Three of them were not related to diabetes. 32
      patients had diabetic foot ulcers (75% males). The implementation of screening
      for diabetic complications was very successful. Based on the results, an evidence
      based disease management programme can be started focussing especially on
      improved tertiary prevention of diabetic complications.

PMID- 10939156
TI  - [Priority of health or treatment problems as themes of international guideline
      programs. Proposition of the Guideline Clearing House on the evaluation of
      guidelines].

PMID- 10939155
TI  - [Prognosis of diabetes. 1905].

PMID- 10939157
TI  - [The epidemiology of constipation].

PMID- 10939158
TI  - [The pathophysiology of chronic constipation].

PMID- 10939159
TI  - [Defecation disorders as the cause of constipation].

PMID- 10939160
TI  - [Constipation in neurological diseases].

PMID- 10939161
TI  - [Constipation in geriatric patients].

PMID- 10939162
TI  - [Constipation and the psyche].

PMID- 10939163
TI  - [The pharmacological therapy of constipation].

PMID- 10939164
TI  - [Dietary fiber in the therapy of constipation].

PMID- 10939165
TI  - [Surgical interventions in constipation].

PMID- 10939166
TI  - Complexity of the neuroendocrine system.
AB  - This paper summarizes briefly the numerous connections and mechanisms existing
      within the neuroendocrine system. In the last decades it became clear that
      besides the originally postulated basic mechanisms there are several other, such
      as autocrine and paracrine mechanisms within the glands, bidirectional neural
      connections between the target endocrine glands and the hypothalamus and lower
      brainstem, which are of functional significance. Further we learned that the
      organization of the neural structures involved is much more complicated than
      originally thought. In addition, it turned out that the neuroendocrine system and
      the immune system are closely and intimately linked to each other. The available
      informations indicate clearly that a physiological integration exists between the
      nervous, the endocrine and immune systems.

PMID- 10939167
TI  - [Role of chloride transporters and water channels in autosomal dominant
      polycystic kidneys].
AB  - The molecular identification of several transporters has allowed a better
      understanding of the mechanism involved in cyst fluid accumulation in the
      autosomal dominant polycystic kidney disease (ADPKD). This fluid secretion is
      mediated by CL- secretion, the latter process being stimulated by cyclic AMP. At
      the cellular level, CL- secretion is carried out by a basolateral, bumetanide
      sensitive cotransporter, organized in series with an apical CFTR channel. The
      accumulation of CL- in the cyst lumen attracts NA+ (electric coupling) and water
      (osmotic coupling), the movement of the latter being partially mediated by
      aquaporins. The understanding of cyst fluid secretion mechanisms will be helpful
      to elaborate new therapeutic strategies aiming at slowing cyst expansion and
      preserving renal function.

PMID- 10939168
TI  - [Travel medicine].
AB  - Intercontinental travel is a source of problems concerning health. This type of
      travel involves an increasing number of persons of different ages and conditions.
      It is increasingly frequent and reaches for destinations which are still more
      distant. The study of the prevention and of the treatment of these problems,
      which are not infectious in the highest number of cases, has led to the
      appearance of "Travel Medicine", which is increasingly being organised. A number
      of problems, which are hardly if at all studied in other disciplined, come under
      this heading.

PMID- 10939169
TI  - [Physiopathological disorders related to extracorporeal circulation. Pathogenesis
      and modes of prevention].
AB  - During heart surgery, several humoral cascades (coagulation, complement,
      kallicrein-kinin, cytokines, fibrinolysis) and several cell systems (platelets,
      neutrophils, endothelial cells, ...) are activated. Numerous contributing factors
      have been reported: blood contact with foreign surfaces of the extracorporeal
      circuits, blood-air interface, lung and myocardial ischemia-reperfusion after
      unclamping, hypothermia, shear stresses, ... A post-perfusion syndrome may
      develop which include miscellaneous symptoms: coagulation disturbances and
      bleeding, neurological alterations, inflammatory syndrome, and, in extreme cases,
      multisystemic organ failure. Even if the present mortality of cardiac surgery is
      low, several approaches have been proposed to reduce such activations. They are
      based on changing in the circuit design, or in the composition of the luminal
      surfaces of the tubing and oxygenator, on improvement of the operative technique,
      and on modifications of the perfusion technique. Pharmacological agents are also
      used (anti-inflammatory drugs, corticoids, serine proteases inhibitor (aprotinin,
      ...). Nevertheless, the development of more biocompatible surfaces seems a
      promising goal.

PMID- 10939171
TI  - [Faces of a century].

PMID- 10939170
TI  - [The brain, movement and space].
AB  - The combination, in humans, of methods of experimental Psychology, of brain
      imagery by position tomography, and functional MRI, and in animals of fine
      methods of neuronal recordings, has allowed us to reveal the neural mechanisms of
      the control of gaze. Thus is now available as important knowledge which can be
      used in Neuro-Ophthalmology for the understanding of the deficits of gaze control
      and in Neuro-Otology for the understanding of the vestibular disorders. We have
      also explored the neural basis of spatial memory and spatial disorientation such
      as observed in psychiatric symptoms as agoraphobia. Here again through a
      combination of neuronal recordings in the rat, brain imagery in normal human and
      studies with neurological patients, we have discovered some of the mechanisms
      which are involved in the memory of space during navigation tasks. In particular
      we have shown the role of the limbic system and of parieto-frontal systems in
      this processes. These results open new avenues in Neurology for the understanding
      of symptoms such as spatial neglect or topographic memory or perturbation in the
      control of posture and locomotion.

PMID- 10939172
TI  - A clinical profile to predict decision making, risk behaviors, clinical status,
      and health-related quality of life for cancer-surviving adolescents. Part 1.
AB  - The purpose of this two-part series is to describe a multifactorial model of
      clinical factors predicting decision-making quality, risk behaviors, clinical
      status, and health-related quality of life for cancer-surviving adolescents. This
      model was developed as a clinical profile to help health professionals in better
      identifying cancer-surviving adolescents at highest risk for substance use.
      Findings in the literature and results from the program of research by the author
      are presented to support the conceptualization of the model. In part 1, support
      for the antecedent predictors, both primary and secondary factors, is presented.
      Part 2 addresses decision making as a mediator, risk motivation as a moderator,
      and the expected outcomes related to risk behaviors, clinical status, and quality
      of life. In addition to describing the first part of the clinical profile in part
      1, the background, theoretical basis of the model, and definitions of the model
      constructs also are provided.

PMID- 10939173
TI  - Perceived risk and help-seeking behavior for breast cancer. A Chinese-American
      perspective.
AB  - Delay in the diagnosis and treatment of breast cancer diminishes a woman's chance
      of survival. How do women decide whether and when to seek an evaluation of breast
      symptoms that may signal breast cancer? Prior studies of African-American, white,
      and Latino women have described a number of critical factors associated with
      making the judgment to delay, but at this writing, there have been no studies
      factors influencing Chinese-American women. By means of focus group methods in
      English, Mandarin, and Cantonese, a sample of 45, predominantly first-generation
      Chinese-American women explained their understanding of breast cancer risk and
      their likelihood of delaying versus seeking evaluation of self-discovered breast
      symptoms. There was much congruence with the ideas of other American women
      despite the differing cultural heritage. Unique to these Chinese Americans was a
      sense of invulnerability to breast cancer, a linking of cancer to tragic luck,
      and the predominant likelihood of delay. To preserve modesty and to conserve
      wealth and time, many study participants favored using Chinese medicine and
      delaying Western therapies. This study suggests ways by which health care
      providers must approach guidelines for breast cancer early detection in this
      population.

PMID- 10939174
TI  - Comparison between African-American and white women in their beliefs about breast
      cancer and their health locus of control.
AB  - The purpose of this study was to examine the health beliefs of African-American
      and white women about breast cancer and locus of control, using the health belief
      model and the health locus of control construct. The Health Screening
      Questionnaire, developed by Sugarek, Deyo, and Holmes, was used to collect self
      report data about health beliefs related to breast cancer and health locus of
      control. Participants included 197 white and 152 African-American women, between
      the ages of 19 and 93, recruited from various settings in central Florida.
      Significant differences were found between the two groups on all of the health
      beliefs about cancer items. The African-American women were significantly more
      likely to believe in chance, or to depend on powerful others for their health.
      Perceived susceptibility to cancer, doubts about the value of early diagnosis,
      and beliefs about the seriousness of breast cancer all were significantly
      associated with powerful other scores among African-American women. There was no
      relation between health beliefs and years of education for African-American
      women, but for white women, those with the least education were more likely to
      believe that death was inevitable with a cancer diagnosis. These results add to
      the information needed for the development of effective programs aimed at
      increasing breast cancer screening among African-American women.

PMID- 10939175
TI  - The effectiveness of the comprehensive coping strategy program on clinical
      outcomes in breast cancer autologous bone marrow transplantation.
AB  - Patients with breast cancer who undergo autologous bone marrow/peripheral blood
      stem cell transplantation (ABMT) cope not only with a life-threatening medical
      treatment, but also with multiple, interrelated symptoms including pain, fatigue,
      psychological distress, and nausea. The purpose of this study was to determine,
      in a randomized controlled clinical trial, whether a comprehensive coping
      strategy program (CCSP) was effective in significantly reducing pain, fatigue,
      psychological distress, and nausea in patients with breast cancer who underwent
      ABMT. The CCSP was composed of preparatory information, cognitive restructuring,
      and relaxation with guided imagery. Randomization placed 52 patients in the CCSP
      treatment group and 58 patients in the control group. The CCSP was found to be
      effective in significantly reducing nausea as well as nausea combined with
      fatigue 7 days after the ABMT when the side effects of treatment were most
      severe. These results are important given the high incidence of nausea and
      fatigue in the ABMT population. The CCSP-treated group experienced mild anxiety
      as compared with the control group who reported moderate anxiety. The greatest
      effectiveness of CCSP may correspond to the time of the greatest morbidity for
      patients with breast cancer who have undergone ABM.

PMID- 10939176
TI  - The research nurse role in a clinic-based oncology research setting.
AB  - Public demand and government support for evaluating new cancer drugs and methods
      in a more timely manner have significantly affected clinical research programs.
      To meet these demands, it is critical to have research personnel with an
      appropriate skill mix to ensure that clinical trials are conducted safely and
      effectively, while scientific integrity is maintained. This article describes the
      development and integration of the research nurse role within an oncology
      research program in a large outpatient oncology clinic. Methods for evaluating
      the research nurse role included literature review, analysis of job descriptions,
      and dialogue with research staff, oncology staff, and a clinical nurse
      specialist. A Review of the Nurse Practice Act of Wisconsin and the Oncology
      Nursing Society standards provided license and practice standards. Similarities
      and differences between the roles of the research nurse and the chemotherapy
      nurse are analyzed. Complementary roles and functions are identified, and areas
      of role overlap are defined. This report expands the limited current literature
      regarding this subject. The findings provide the reader with a framework for
      evaluating the roles of registered nurse personnel in a clinical setting.
      Although each institution has unique characteristics or research needs, the
      method used to address the reported program is transferable.

PMID- 10939177
TI  - Participant characteristics before and 4 months after attendance at a family
      caregiver cancer education program.
AB  - Recent trends in health care have placed an increased burden on cancer
      caregivers. In response, nurses and social workers have been taught to implement
      a 6-hour psychoeducation program for cancer caregivers that addresses symptom
      management, psychosocial support, and resource identification. Longitudinal data
      from a convenience sample of 187 cancer caregivers who attended the program are
      reported. Data were collected before attendance and 4 months later. Findings
      confirm the chronic and consuming nature of cancer caregiving. Data indicate that
      perception of burden did not worsen even when caregiving tasks increased in
      intensity. Caregiver perceptions of their own health actually improved over time.
      In addition, the number of caregivers who said they were well informed and
      confident about caregiving after program attendance increased over time. Further
      study that randomizes caregivers to intervention/control groups is needed to
      substantiate the role of similar programs in enhancing caregiver skills and
      minimizing caregiver burden over time.

PMID- 10939178
TI  - An interview study of men discovering testicular cancer.
AB  - Testicular cancer affects men between 15 and 45 years old. The aim of this study
      was to show how men with testicular cancer discover their cancer, react to
      physical changes, and take action. In the follow-up phase, 21 who had undergone
      surgery for testicular cancer were interviewed. The results show clearly that the
      men focus on their physical pain. The progress from the discovery of changes in
      the testicular glands to medical care can be divided into three phases. In the
      first phase, "something has happened," the men consider the changes and try to
      define the reasons. In the second phase, "facing the situation," they consider
      the situation and decide whether to talk to someone. In the third phase, "seeking
      medical help," it is a question of seeking help and being confronted by the
      medical diagnosis. In terms of time, the progression in the current study took
      from 1 day to 1 year. The men sought help when complications arose that made
      normal daily functions difficult. Six of the men suspected that the cause of
      their problems was cancer. Almost half of the participants in this study,
      including the six who suspected cancer, did not talk to anyone before they
      decided to seek medical help. The men who did talk to other people did not seek
      medical help any more quickly than the other men. None of the men routinely
      inspected their bodies.

PMID- 10939179
TI  - An overview of psychosocial support services. Resources for healing.
AB  - Cancer has the potential of threatening all of a person's resources: physical,
      psychological, social, spiritual, and economic. It is as if the experience of
      cancer takes on a life cycle of its own that starts with the shock of diagnosis
      and continues well beyond the completion of treatment. Psychosocial support
      services of various types need to be made available throughout the cancer
      experience. Participation in these services affords people the opportunity to
      learn positive coping skills, to recognize that they are not alone, to discover
      how to enjoy living in the present, and to attach a different meaning to the
      words "hope" and "healing." Restoring a sense of wholeness to one's mind, body,
      and spirit is equally as important as receiving the most effective therapy for
      the cancer.

PMID- 10939180
TI  - Oncology ward nurses' perspectives of family grief and a supportive telephone
      call after the death of a significant other.
AB  - To improve family nursing in oncology wards, a new nursing intervention was
      created: a supportive telephone call after the death of the patient. Nurses who
      participated in the intervention kept diaries after the call (n = 95). Data were
      collected also from hospital records. The numerical data were analyzed by using
      descriptive statistical analysis and the qualitative data by using content
      analysis. In the diaries, nurses described family grief and mourning as well as
      content of the supportive telephone call after the death of a family member.
      Multidimensionality described the family member's grief. The funeral was an
      important part of the culturally dictated mourning. Support for the family during
      the patient's last days at the hospital was meaningful with regard to the grief
      and the onset of coping. Closeness of the nurse-family relationship varied from a
      close relationship to an uncertain one. A supportive atmosphere during the call
      made it possible for the survivor to ask questions and talk. During the call,
      nurses were able to evaluate the family's coping. They also got feedback
      concerning the nursing care delivered. The call served as a finishing analysis of
      the family nursing process. The implications of these results for supporting the
      grieving family by a telephone intervention are considered.

PMID- 10939181
TI  - Further increase in prevalent diagnosed HIV infections in the United Kingdom
      1999.

PMID- 10939182
TI  - AIDS and HIV infection in the United Kingdom: monthly report.

PMID- 10939183
TI  - Using a relational database to support nursing research.

PMID- 10939184
TI  - Clinical information system implementation. Challenges across two merged
      hospitals.

PMID- 10939185
TI  - Evaluation of the effectiveness of a Web-based graduate epidemiology course.
AB  - An online epidemiology course was developed, implemented, and evaluated for
      graduate nursing students through the collaborative efforts of nursing faculty
      and information, education, and instructional design staff of the library at a
      health sciences university. This epidemiology course is a core curriculum course
      for graduate nursing students. The course was piloted with 14 students (one
      student in Romania); the initial online offering ran concurrently with a
      traditional classroom section. Extensive evaluation data were collected and
      analyzed to compare the effectiveness of the classroom and distance-learning
      formats. Areas of evaluation included objective measures, such as midterm and
      final examination scores and content analysis comparisons, as well as subjective
      ratings by the students of time commitments, course objectives, technical aspects
      of the web-based course, areas of satisfaction or dissatisfaction, and self
      confidence regarding epidemiology and computer skills. Recommendations for course
      development, implementation, and evaluation for similar distance-learning courses
      will be included.

PMID- 10939186
TI  - Online support for caregivers. Analysis of an Internet Alzheimer mailgroup.
AB  - Alzheimer's disease affects more than four million Americans and ranks as the
      fourth leading cause of death in adults. To deal with the stresses of constant
      caregiving, family members of patients with Alzheimer's disease are encouraged to
      participate in support groups. However, geographic and time constraints combined
      with lack of substitute caregivers may preclude attendance at traditional support
      groups. Internet-based groups offer caregivers the opportunity to interact with
      other caregivers for guidance, information, and encouragement. This project
      examines the content and themes of 532 messages posted on a public Alzheimer
      mailgroup during 20 days of 1998. Members used the mailgroup to find and proffer
      information, share experiences and opinions, and provide encouragement. By
      becoming aware of the potential advantages that online support groups offer to
      caregivers, nurses can encourage Alzheimer caregivers to use online groups as an
      empowering and practical adjunct to traditional caregiver support.

PMID- 10939187
TI  - Evaluation of online course discussions. Faculty facilitation of active student
      learning.
AB  - Graduate nursing faculty evaluated their initial experiences with online course
      discussions after making the transition from traditional use of weekly face-to
      face classroom discussions to primarily computer-based interactions with students
      at distant sites. The online discussion data were analyzed qualitatively. The
      ways the faculty member communicated to facilitate active student involvement in
      the online discussions were coded. Six categories were identified that describe
      the ways the faculty member communicated to facilitate active student involvement
      in online discussions: assist with navigation, explain expectations, clarify
      faculty role, stimulate critical thinking, share expertise, and provide
      encouragement. Examples of each were provided to demonstrate ways faculty
      promoted student learning in online discussions.

PMID- 10939188
TI  - A compendium of information processing functions in nursing. Development and
      pilot study.
AB  - Before introducing computers or other tools to support nursing care, it is
      important to have a clear picture of the information processing functions
      required in this area. This article presents a compendium of information
      processing functions used in nursing. This compendium can be used to support
      management of information systems in planning and monitoring nursing information
      systems. The article describes the development of the first version of this
      compendium and its evaluation in a pilot study. The results of this evaluation
      show that the compendium can be used to assess the quality of information
      processing in nursing.

PMID- 10939189
TI  - Computer knowledge, attitudes, and skills of nurses in People's Hospital of
      Beijing Medical University.
AB  - The first Chinese Hospital Information Systems (HIS) was used as a pilot project
      at People's Hospital, of Beijing Medical University (BMU). To assess the computer
      knowledge, attitudes, and skills of nurses working in the hospital, and to
      examine the relationships among these factors, 169 staff nurses working on
      clinical units were surveyed by proportionate stratified random sampling.
      Computer knowledge, attitudes, and skills were measured, by a nurses' computer
      knowledge questionnaire (NCKQ), nurses' computer attitude scale (NCAS), and
      nurses' computer skill scale (NCSS), respectively, developed by the
      investigators. Data analysis showed that the overall computer knowledge and
      skills of nurses were at moderate levels and the computer attitudes were neutral.
      Nurses' computer skills were significantly and positively correlated with both
      computer knowledge and computer attitudes; however, no significant correlation
      was found between computer knowledge and computer attitudes. Strategies to
      enhance nurses' computer knowledge, attitudes, and skills were proposed.

PMID- 10939190
TI  - [Acetylcholinesterase activity during pregnancy and in the newborn].
AB  - OBJECTIVES: Our purpose was to determine levels of acetyilcholinesterase (AchE)
      activity in total blood of women during pregnancy, and liverborns, and to analyze
      the correlation of the enzymatic activity between the capillary and venous
      sample. PATIENTS, MATERIAL, AND METHODS: We included 205 samples from pregnant
      (22), second (25), third trimester (36), full term pregnancy (65), non-pregnant
      women (28), and from Newborns (29). A bivaried analysis was used to analyse the
      AchE activity and its association with gestational age, body mass index, tobacco
      addiction, and use of pesticides at home, and hemoglobin concentration. RESULTS:
      Women at childbirth and at third trimester showed a significant increase in AcE
      levels by 5.75 + 1.15 U/mL and 4.98 +/- 0.87 U/mL respectively, respect to levels
      from non-pregnant women (4.59 +/- 0.79 U/mL). Activity in cord's blood was
      significatively minor (3.78 +/- 0.56 U/mL) compared with levels in non-pregnant
      women. There was no difference in AchE activity by tobacco addiction, hemoglobin
      levels, and use of insecticides at home. AchE activity by capillary and venous
      punction showed a correlation of 0.68 with p < 0.01 and IC 95% = 0.5171-0.8476.
      CONCLUSIONS: Enzymatic activity showed a normal distribution and could be
      considered like values from a non-exposure population. We determined that
      possible confounding factors like tobacco addiction and use of pesticides at home
      have no significant effects over AchE activity. Our results are important as
      reference values for studies about AchE activity in women from populations
      predominantly exposed to pesticides during gestation.

PMID- 10939191
TI  - [Within the limits of viability: the dilemma of the obstetrician. A 5-year
      experience at a perinatal care center].
AB  - The study was performed in order to establish the obstetric factors that
      influence survival of newborns whose birth weight is under 1000 g. All medical
      records of babies with such birth weight, born alive at the Instituto Nacional de
      Perinatologia in Mexico City during the period from 1991 to 1996 were revised.
      Babies with congenital malformations, cromomosomopathies or those who after birth
      were referred to another medical center were excluded. Survival status was used
      to form two study groups: those who were discharged alive and those who died
      during their hospital stay. Different obstetric conditions on management were
      compared between these two groups. Statistical Analysis was performed through t
      test, chi square or exact Fisher's test. Two hundred and ninety two cases were
      included out of 294. Sixty nine (25.4%) survived while 203 (74.6%) died during
      their hospitalization. Several obstetric conditions were found to have
      statistical differences between survivors (S) and non survivors (NS): cervical
      dilatation on admittance to hospital (1.6 cm among S and 2.7 among NS), cervical
      dilatation prior to resolution (3.3 cm S vs 4.9 cm NS), gestational age (28.3 vs
      27 weeks). Newborn conditions also showed significant statistical differences as
      in birth weight (867.1 vs 795.5 g), 1 minute Apgar (4.1 vs 2.5), and 5 min Apgar
      (6.9 vs 5). Use of antepartum steroids showed a striking difference between
      groups while duration of labor, usage of oxitocin and way of delivery showed no
      statistical differences. Gestational age (over 28 weeks), birth weight (above 867
      g) and the use of antepartum steroids are of extreme importance in the survival
      status of babies born weighting less than 1000 g.

PMID- 10939193
TI  - [Prenatal diagnosis of bronchopulmonary sequestration at the 26th week of
      gestation: report of a case].
AB  - A case report of a 18 years-old women on her first pregnancy, (26 weeks). US
      detected a live fetus with pulmonary sequestration diagnosis. On week 39 vaginal
      delivery occurred. A live newborn, Apgar 7-8 and Silverman 4-4 (one minute and
      five minutes respectively) was obtained. When diagnoses was confirmed, a surgical
      resection was performed (five days) and the child died at day-15 due to
      nosocomial sepsis. This case shows the convenience of prenatal diagnosis for
      management decisions.

PMID- 10939192
TI  - [Usefulness of the relationship between follicular stimulating hormone,
      deoxypyridinoline, estradiol, and inhibin as decision criterion for starting
      replacement hormone therapy in climacteric and its correlation with
      symptomatology].
AB  - INTRODUCTION: There is no precise indication for the adequate moment to start
      hormone replacement therapy (HRT). OBJECTIVE: To evaluate several indexes
      obtained with serum levels of follicle stimulating hormone (FSH), estradiol (E2),
      estrone (E) and inhibin and urinary deoxypyridinoline (DPD) and correlate them
      with Kupperman index as decision criteria for the beginning of hormone
      replacement therapy (HRT) in the climatery. MATERIAL AND METHODS: In 53 patients
      the presence and intensity of climateric symptoms was evaluated using the
      modified Kupperman's index. They were divided in: premenopausal, perimenopausal
      or postmenopausal. groups FSH, E2, E and inhibin blood levels, as well as urinary
      DPD were measured. Several indexes were calculated, and then were compared
      between the groups and correlated with Kupperman's index score. Statistical
      analysis. Kruskall-Wallis and Mann-Whitney U test were done, as well as
      Spearman's correlation analysis. RESULTS: After comparing the indexes, the Log
      FSH/E2, Log FSH/E2, Log FSH/E2/E, Log FSH(DPD)/E2, Log FSH(DPD)/E2/E and Log FSH
      (DPD)/Inhibin(E2) were significantly greater in postmenopausal group. Only there
      was a significant correlation between Log FSH/Inhibin(E2) index, and Log
      FSH(DPD)/Inhibin(E2) index with Kupperman's index. CONCLUSIONS: Log FSH
      (DPD)/E2/E index seems to be the more suitable, index because it had a
      progressive increase as the patients advanced towards postmenopause. The afore
      mentioned index must be validated with a greater number of patients to assess a
      cut point that can define in which patients HRT must be administered.

PMID- 10939194
TI  - [Causes for accepting or not accepting contraceptive methods in the immediate
      postabortion].
AB  - OBJECTIVE: To determine the causes that motivate acceptance or not-acceptance of
      contraceptiva methods in the immediate post abortion period. Material and
      methods. 191 questionnaires were applied to immediate post abortion patients, in
      the "Luis Castelazo Ayala" Gynecology and Obstetrics Hospital of the Instituto
      mexicano del Seguro Social. Patients were divided by two groups: acceptants (n =
      75) and not-acceptants (n = 116). Both groups were compared with Student's t test
      and contrast of proportions. RESULTS: There were not significant differences in
      the general characteristics of both groups like age, age at menarche, beginning
      of sexual intercourse, age of marriage or free union, school grade, age at first
      pregnancy, number of pregnancies, gestational age of the last pregnancy that
      ended in abortion, previous use of contraceptiva methods and previous experience
      with them and whether or not they wanted a new pregnancy. The contraceptive
      method was offered to all patients in the acceptant group. Information was given
      to 45.33% of them and was considered satisfactory in 75.00%. In contrast, not
      acceptants that received information were only 26.72% (p < 0.05) and all of them
      (100.00%) considered it inadequate (p < 0.05). In 20.68% of the women the method
      was not offered (p < 0.05). Medical contraindications were present in only 6.03%.
      The accepted methods were intrauterino device (64.00%), parentheral methods
      (16.00%), oral contraceptives (13.33%), surgical sterilization (5.33%) and
      condoms (1.33%). The contraceptive coverage of post abortion patients was 39.27%
      in this period. CONCLUSIONS: The use of contraceptive methods in post abortion
      patients can be increased if it is offered systematically to all patients who
      have had an abortion. Information given to patients must be understandable and
      sufficient to dissipate fears and ciarify doubts regarding the contraceptive
      method; contraceptive options must be offered according to the reproductive
      expectancies and using the informed consent to reinforce the acceptance of the
      chosen method.

PMID- 10939195
TI  - [Androgen-producing steroid cell ovarian tumor. Report of a case].
AB  - Ovarian Tumors with Endocrine Repercussion make-up 5% of neoplasms in this gland,
      occupying the first place are the estrogen-producing tumors, in the second place
      are the androgen-producing tumors, progesterone, corticosteroids and renin are
      exceptional. In these tumors' nomenclature has existed a kind of synonyms that
      create confusion about their histogenesis and their difficult use in the
      literature. CASE REPORT: A 23 yr-old woman with opsomenorrhea of several years
      evolution, secondary amenorrhea, deep voice and progressive hirsutism. Weight:
      98.500 kg. Height: 1.74 m. Body Mass Index (BMI): 32.61 (kg/m2). Vellus hair in
      the face (beard and moustache), android distribution in abdomen, forearms, thighs
      and legs (Ferriman score of 20), acne and bilateral breast involution. All
      paraclinic exams were negative. Human chorionic gonadotropin quantification in
      urine of 24 hours was negative. X-Ray: Right ovarian tumor was demonstrated with
      pelvic ultrasound and computerized axial tomography of abdomen. Cytogenetic study
      expressed 46 XX chromosomes. Presurgery endocrinologic studies were: total and
      free testosterone: 3.55 ng/mL and 14.30 pg/mL, respectively. Insulin: 43.3
      microU/mL and C peptide: 5.7 ng/mL. The glucose tolerance test demonstrate
      intolerance to carbohydrates. During operation, the hormone levels in the right
      ovarian vein were: total and free testosterone of 2.70 ng/mL and 12.70 pg/mL
      respectively, which normalized after 12 hours of surgery. Other steroid hormones
      were normal. After six months of surgery the patient had Ferriman score of 10 and
      eumenorrhea. Weight: 98.100 kg, glucose tolerance test and basal hormone levels
      were normal. Electron Microscopy showed characteristic data of a steroid
      producing tumor without crystalloids of Reinke.

PMID- 10939198
TI  - Brief of the Attorney General of the state of Nebraska in Stenberg v. Carhart.

PMID- 10939197
TI  - [Transabdominal cerclage in the management of cervical incompetence].
AB  - The Transabdominal Cerclage in the Cervical Incompetence. The purpose of this
      study was to assess the transabdominal cerclage indications at the Instituto
      Nacional de Perinatologia. A retrospective study was carried on in order to
      evaluate fetal outcome in all patients with transabdominal cerclages. Since 1997
      seven transabdominal cerclages were performed. The primary indication was
      unsuccessful previous vaginal cerclage. All seven patients delivered at term. The
      rate of live births before the procedure was 5.2% compared to 85.8% after the
      transabdominal cerclage. There was one still birth a the gestational of 37.2 in a
      woman with preeclampsia. Five newborns were small for gestational age. In our
      study the transabdominal cerclage, under strict indications, offers a high fetal
      survival rate with a minimum of complications in patients with a poor obstetric
      history due to cervical incompetence and unsuccessful vaginal cerclage.

PMID- 10939196
TI  - [Clomiphene acetate and prednisone: alternative approach for the management of
      patients with chronic anovulation and clomiphene treatment failure].
AB  - Chronic anovulation is a common neuroendocrine cause of infertility.
      Pharmacological management of such condition includes the use of clomiphen
      citrate (CC), which is the most utilized of the ovulation inductors. Clinical
      efficacy of CC provides ovulation rates of around 70%. Those patients who did not
      respond are candidates to receive gonadothrophin treatment, which will increase
      costs and the risk of ovarian hyperstimulation and multiple pregnancies. Because
      of that, new alternative treatments have been assayed, such as the concomitant
      use of dexametasone. This alternative has improved the response, but its use has
      been limited because the side effects of this treatment overcome their benefits.
      Another alternative is the use of prednisone throughout the menstrual cycle
      together with CC administered in pre-established days. This treatment is expected
      to improve the response without adding side effects. However, its clinical
      efficacy and clinical tolerance have not been studied. In this study we used CC
      and prednisone in a sample of patients diagnosed with infertility and chronic
      anovulation, and with previous failure to the treatment with CC. Patients were
      compared to a group of women with similar characteristics but who received
      additional cycles of CC. The group that received prednisone and CC increased
      their ovulation rates in 38%, compared to 8% in women that received only CC.
      Similarly, pregnancy rates increased 20% in the CC plus prednisone group while
      the group that received CC alone remained in 0 pregnancies. In the total sample,
      tolerance to treatment was adequate. There were no side effects associated to the
      use of prednisone. We conclude that the treatment with CC plus prednisone is an
      alternative treatment for patients in which the classical treatment with CC has
      failed.

PMID- 10939199
TI  - Brief of Dr. Carhart et al. in Stenberg v. Carhart.

PMID- 10939200
TI  - Oral arguments before the United States Supreme Court in Stenberg v. Carhart.

PMID- 10939201
TI  - State-space modeling of the relationship between air quality and mortality.
AB  - A portion of a population is assumed to be at risk, with the mortality hazard
      varying with atmospheric conditions including total suspended particulates (TSP).
      This at-risk population is not observed and the hazard function is unknown; we
      wish to estimate these from mortality count and atmospheric variables.
      Consideration of population dynamics leads to a state-space representation,
      allowing the Kalman Filter (KF) to be used for estimation. A harvesting effect is
      thus implied; high mortality is followed by lower mortality until the population
      is replenished by new arrivals. The model is applied to daily data for
      Philadelphia, PA, 1973-1990. The estimated hazard function rises with the level
      of TSP and at extremes of temperature and also reflects a positive interaction
      between TSP and temperature. The estimated at-risk population averages about 480
      and varies seasonally. We find that lags of TSP are statistically significant,
      but the presence of negative coefficients suggests their role may be partially
      statistical rather than biological. In the population dynamics framework, the
      natural metric for health damage from air pollution is its impact on life
      expectancy. The range of hazard rates over the sample period is 0.07 to 0.085,
      corresponding to life expectancies of 14.3 and 11.8 days, respectively.

PMID- 10939202
TI  - Exposure of chronic obstructive pulmonary disease patients to particulate matter:
      relationships between personal and ambient air concentrations.
AB  - Mot time-series studies of particulate air pollution and acute health outcomes
      assess exposure of the study population using fixed-site outdoor measurements. To
      address the issue of exposure misclassification, we evaluate the relationship
      between ambient particle concentrations and personal exposures of a population
      expected to be at risk of particle health effects. Sampling was conducted within
      the Vancouver metropolitan area during April-September 1998. Sixteen subjects
      (non-smoking, ages 54-86) with physician-diagnosed chronic obstructive pulmonary
      disease (COPD) wore personal PM2.5 monitors for seven 24-hr periods, randomly
      spaced approximately 1.5 weeks apart. Time-activity logs and dwelling
      characteristics data were also obtained for each subject. Daily 24-hr ambient
      PM10 and PM2.5 concentrations were measured at five fixed sites spaced throughout
      the study region. SO4(2-), which is found almost exclusively in the fine particle
      fraction and which does not have major indoor sources, was measured in all PM2.5
      samples as an indicator of accumulation mode particulate matter of ambient
      origin. The mean personal and ambient PM2.5 concentrations were 18 micrograms/m3
      and 11 micrograms/m3, respectively. In analyses relating personal and ambient
      measurements, ambient concentrations were expressed either as an average of the
      values obtained from five ambient monitoring sites for each day of personal
      sampling, or as the concentration obtained at the ambient site closest to each
      subject's home. The mean personal to ambient concentration ratio of all samples
      was 1.75 (range = 0.24 to 10.60) for PM2.5, and 0.75 (range = 0.09 to 1.42) for
      SO4(2-). Regression analyses were conducted for each subject separately and on
      pooled data. The median correlation (Pearson's r) between personal and average
      ambient PM2.5 concentrations was 0.48 (range = -0.68 to 0.83). Using SO4(2-) as
      the exposure metric, the median r between personal and average ambient
      concentrations was 0.96 (range = 0.66 to 1.0). Use of the closest ambient site
      did not improve the median correlation of the group for either PM2.5 or SO4(2-).
      All pooled analyses resulted in lower correlation coefficients than the median
      correlation coefficient of individual regressions. Personal SO4(2-) was more
      highly correlated with all ambient measures than PM2.5. Inclusion of time
      activity and dwelling characteristics data did not result in a useful predictive
      regression model for PM2.5 personal exposure, but improved the model fit from
      simply regressing against ambient concentration (R2 = 0.27). The model for SO4(2
      ) was predictive (R2 = 0.82), as personal exposures were largely explained by
      ambient levels. These results indicate a relatively low correlation between
      personal exposure and ambient PM2.5 that is not improved by assigning exposure to
      the closest ambient monitor. The correlation between personal exposure and
      ambient concentration is high, however, when using SO4(2-), an indicator of
      accumulation mode particulate matter of ambient origin.

PMID- 10939203
TI  - Method comparisons for particulate nitrate, elemental carbon, and PM2.5 mass in
      seven U.S. cities.
AB  - Methods that measure PM2.5 mass, total particulate NO3-, and elemental carbon
      (EC) were evaluated in seven U.S. cities from 1997 to 1999. Sampling was
      performed in Bakersfield, CA; Boston, MA; Chicago, IL; Dallas, TX; Philadelphia,
      PA; Phoenix, AZ; and Riverside, CA. Evaluating and validating methods that
      measure the components of fine mass are important to the effort of establishing a
      speciation-monitoring network. The Harvard Impactor (HI), which measures fine
      particle mass, showed excellent agreement (r2 = 0.99) with the PM2.5 Federal
      Reference Method (FRM) for 81 24-hr samples in Riverside and Bakersfield. The HI
      also showed good precision (4.8%) for 243 24-hr collocated samples over eight
      studies. The Aethalometer was employed in six of the sampling locations to
      measure black carbon (BC). These values were compared to EC as measured from a
      quartz filter using thermal analysis. For the six cities combined, the two
      methods were highly correlated (r2 = 0.94; 187 24-hr samples); however, the BC
      values were approximately 24% less than the EC measurements consistently across
      all six cites. This compares well to results observed for EC/BC measurements
      observed in other semi-urban areas. Particulate NO3- was measured using the
      Harvard-EPA Annular Denuder System (HEADS). This was compared to the NO3-
      measured from the HI Teflon (DuPont) filter to assess NO3- artifacts. Significant
      NO3- losses (approximately 50% of total NO3-) were found in Riverside,
      Philadelphia, and Boston, while minimal artifacts were observed in the other
      sites. Two types of HEADS configurations were employed in five cities. One system
      used a Na2CO3-coated glass fiber filter, and the other type used a nylon filter
      to collect volatilized NO3- from the Teflon filter. The HEADS with the Na2CO3
      coated filter consistently underestimated the total particulate NO3- by
      approximately 20% compared to the nylon HEADS.

PMID- 10939204
TI  - Characterization of fine particulate matter produced by combustion of residual
      fuel oil.
AB  - Combustion experiments were carried out on four different residual fuel oils in a
      732-kW boiler. PM emission samples were separated aerodynamically by a cyclone
      into fractions that were nominally less than and greater than 2.5 microns in
      diameter. However, examination of several of the samples by computer-controlled
      scanning electron microscopy (CCSEM) revealed that part of the PM2.5 fraction
      consists of carbonaceous cenospheres and vesicular particles that range up to 10
      microns in diameter. X-ray absorption fine structure (XAFS) spectroscopy data
      were obtained at the S, V, Ni, Fe, Cu, Zn, and As K-edges and at the Pb L-edge.
      Deconvolution of the X-ray absorption near edge structure (XANES) region of the S
      spectra established that the dominant molecular forms of S present were sulfate
      (26-84% of total S) and thiophene (13-39% of total S). Sulfate was greater in the
      PM2.5 samples than in the PM2.5+ samples. Inorganic sulfides and elemental sulfur
      were present in lower percentages. The Ni XANES spectra from all of the samples
      agreed fairly well with that of NiSO4, while most of the V spectra closely
      resembled that of vanadyl sulfate (VO.SO4.xH2O). The other metals investigated
      (i.e., Fe, Cu, Zn, and Pb) also were present predominantly as sulfates. Arsenic
      was present as an arsenate (As+5). X-ray diffraction patterns of the PM2.5
      fraction exhibit sharp lines due to sulfate compounds (Zn, V, Ni, Ca, etc.)
      superimposed on broad peaks due to amorphous carbons. All of the samples contain
      a significant organic component, with the loss on ignition (LOI) ranging from 64
      to 87% for the PM2.5 fraction and from 88 to 97% for the PM2.5+ fraction. Based
      on 13C nuclear magnetic resonance (NMR) analysis, the carbon is predominantly
      condensed in graphitic structures. Aliphatic structure was detected in only one
      of seven samples examined.

PMID- 10939205
TI  - Spatial variability of different fractions of particulate matter within an urban
      environment and between urban and rural sites.
AB  - The spatial variability of different fractions of particulate matter (PM) was
      investigated in the city of Basel, Switzerland, based on measurements performed
      throughout 1997 with a mobile monitoring station at six sites and permanently
      recorded measurements from a fixed site. Additionally, PM10 measurements from the
      following year, which were concurrently recorded at two urban and two rural
      sites, were compared. Generally, the spatial variability of PM4, PM10, and total
      suspended particulates (TSP) within this Swiss urban environment (area = 36 km2)
      was rather limited. With the exception of one site in a street canyon next to a
      traffic light, traffic density had only a weak tendency to increase the levels of
      PM. Mean PM10 concentration at six sites with different traffic densities was in
      the range of less than +/- 10% of the mean urban PM10 level. However, comparing
      the mean PM levels on workdays to that on weekends indicated that the impact of
      human activities, including traffic, on ambient PM levels may be considerable.
      Differences in the daily PM10 concentrations between urban and more elevated
      rural sites were strongly influenced by the stability of the atmosphere. In
      summer, when no persistent surface inversions exist, differences between urban
      and rural sites were rather small. It can therefore be concluded that spatial
      variability of annual mean PM concentration between urban and rural sites in the
      Basel area may more likely be caused by varying altitude than by distance to the
      city center.

PMID- 10939206
TI  - Use of a continuous nephelometer to measure personal exposure to particles during
      the U.S. Environmental Protection Agency Baltimore and Fresno Panel studies.
AB  - In population exposure studies, personal exposure to PM is typically measured as
      a 12- to 24-hr integrated mass concentration. To better understand short-term
      variation in personal PM exposure, continuous (1-min averaging time)
      nephelometers were worn by 15 participants as part of two U.S. Environmental
      Protection Agency (EPA) longitudinal PM exposure studies conducted in Baltimore
      County, MD, and Fresno, CA. Participants also wore inertial impactor samplers (24
      hr integrated filter samples) and recorded their daily activities in 15-min
      intervals. In Baltimore, the nephelometers correlated well (R2 = 0.66) with the
      PM2.5 impactors. Time-series plots of personal nephelometer data showed each
      participant's PM exposure to consist of a series of peaks of relatively short
      duration. Activities corresponding to a significant instrument response included
      cooking, outdoor activities, transportation, laundry, cleaning, shopping,
      gardening, moving between microenvironments, and removing/putting on the
      instrument. On average, 63-66% of the daily PM exposure occurred indoors at home
      (about 2/3 of which occurred during waking hours), primarily due to the large
      amount of time spent in that location (an average of 72-77%). Although not a
      reference method for measuring mass concentration, the nephelometer did help
      identify PM sources and the relative contribution of those sources to an
      individual's personal exposure.

PMID- 10939208
TI  - Systematic biases in measured PM10 values with U.S. Environmental Protection
      Agency-approved samplers at Owens Lake, California.
AB  - From 1993 through 1998, Wedding or Graseby high-volume PM10 samplers were
      collocated with tapered element oscillating microbalance (TEOM) samplers at three
      sites at Owens Lake, CA. The study area is heavily impacted by windblown dust
      from the dry Owens Lake bed, which was exposed as a result of water diversions to
      the city of Los Angeles. A dichotomous (dichot) sampler and three collocated
      Partisol samplers were added in 1995 and 1999, respectively. U.S. Environmental
      Protection Agency (EPA) operating procedures were followed for all samplers,
      except for a Wedding sampler that was not cleaned for the purpose of this study.
      On average, the TEOM and Partisol samplers agreed to within 6%, and the dichot,
      Graseby, and Wedding samplers measured lower PM10 concentrations by about 10, 25,
      and 35%, respectively. Surprisingly, the "clean" Wedding sampler consistently
      measured the same concentration as the "dirty" Wedding sampler through 85 runs
      without cleaning. The finding that the Graseby and Wedding high-volume PM10
      samplers read consistently lower than the TEOM, Partisol, and dichot samplers at
      Owens Lake is consistent with PM10 sampler comparisons done in other fugitive
      dust areas, and with wind tunnel tests showing that sampler cut points can be
      significantly lower than 10 microns under certain conditions. However, these
      results are opposite of the bias found for TEOM samplers in areas that have
      significant amounts of volatile particles, where the TEOM reads low due to the
      vaporization of particles on the TEOM's heated filter. Coarse particles like
      fugitive dust are relatively unaffected by the filter temperature. This study
      shows that in the absence of volatile particles and in the presence of fugitive
      dust, a different systematic bias of up to 35% exists between samplers using
      dichot inlets and high-volume samplers, which may cause the Graseby and Wedding
      PM10 samplers to undermeasure PM10 by up to 35% when the PM10 is predominantly
      from coarse particulate sources.

PMID- 10939207
TI  - Personal exposure to fine particulate matter in elderly subjects: relation
      between personal, indoor, and outdoor concentrations.
AB  - The time-series correlation between ambient levels, indoor levels, and personal
      exposure to PM2.5 was assessed in panels of elderly subjects with cardiovascular
      disease in Amsterdam, the Netherlands, and Helsinki, Finland. Subjects were
      followed for 6 months with biweekly clinical visits. Each subject's indoor and
      personal exposure to PM2.5 was measured biweekly, during the 24-hr period
      preceding the clinical visits. Outdoor PM2.5 concentrations were measured at
      fixed sites. The absorption coefficients of all PM2.5 filters were measured as a
      marker for elemental carbon (EC). Regression analyses were conducted for each
      subject separately, and the distribution of the individual regression and
      correlation coefficients was investigated. Personal, indoor, and ambient
      concentrations were highly correlated within subjects over time. Median Pearson's
      R between personal and outdoor PM2.5 was 0.79 in Amsterdam and 0.76 in Helsinki.
      For absorption, these values were 0.93 and 0.81 for Amsterdam and Helsinki,
      respectively. The findings of this study provide further support for using fixed
      site measurements as a measure of exposure to PM2.5 in epidemiological time
      series studies.

PMID- 10939209
TI  - Comparison of short-term variations (15-minute averages) in outdoor and indoor
      PM2.5 concentrations.
AB  - Measurements of 15-min average PM2.5 concentrations were made with a real-time
      light-scattering instrument at both outdoor (central monitoring sites in three
      communities) and indoor (residential) locations over two seasons in the
      Minneapolis-St. Paul metropolitan area. These data are used to examine within-day
      variability of PM2.5 concentrations indoors and outdoors, as well as matched
      indoor-to-outdoor (I/O) ratios. Concurrent gravimetric measurements of 24-hr
      average PM2.5 concentrations were also obtained as a way to compare real-time
      measures with this more traditional metric. Results indicate that (1) within-day
      variability for both indoor and outdoor 15-min average PM2.5 concentrations was
      substantial and comparable in magnitude to day-to-day variability for 24-hr
      average concentrations; (2) some residences exhibited substantial variability in
      indoor aerosol characteristics from one day to the next; (3) peak values for
      indoor short-term (15-min) average PM2.5 concentrations routinely exceeded 24-hr
      average outdoor values by factors of 3-4; and (4) relatively strong correlations
      existed between indoor and outdoor PM2.5 concentrations for both 24-hr and 15-min
      averages.

PMID- 10939210
TI  - Estimating separately personal exposure to ambient and nonambient particulate
      matter for epidemiology and risk assessment: why and how.
AB  - This paper discusses the legal and scientific reasons for separating personal
      exposure to PM into ambient and nonambient components. It then demonstrates by
      several examples how well-established models and data typically obtained in
      exposure field studies can be used to estimate both individual and community
      average exposure to ambient-generated PM (ambient PM outdoors plus ambient PM
      that has infiltrated indoors), indoor-generated PM, and personal activity PM.
      Ambient concentrations are not highly correlated with personal exposure to
      nonambient PM or total PM but are highly correlated with personal exposure to
      ambient-generated PM. Therefore, ambient concentrations may be used in
      epidemiology as an appropriate surrogate for personal exposure to ambient
      generated PM. Suggestions are offered as to how exposure to ambient-generated PM
      may be obtained and used in epidemiology and risk assessment.

PMID- 10939211
TI  - Assessing the relationship between personal particulate and gaseous exposures of
      senior citizens living in Baltimore, MD.
AB  - We conducted a multi-pollutant exposure study in Baltimore, MD, in which 15 non
      smoking older adult subjects (> 64 years old) wore a multi-pollutant sampler for
      12 days during the summer of 1998 and the winter of 1999. The sampler measured
      simultaneous 24-hr integrated personal exposures to PM2.5, PM10, SO4(2-), O3,
      NO2, SO2, and exhaust-related VOCs. Results of this study showed that
      longitudinal associations between ambient PM2.5 concentrations and corresponding
      personal exposures tended to be high in the summer (median Spearman's r = 0.74)
      and low in the winter (median Spearman's r = 0.25). Indoor ventilation was an
      important determinant of personal PM2.5 exposures and resulting personal-ambient
      associations. Associations between personal PM2.5 exposures and corresponding
      ambient concentrations were strongest for well-ventilated indoor environments and
      decreased with ventilation. This decrease was attributed to the increasing
      influence of indoor PM2.5 sources. Evidence for this was provided by SO4(2-)
      measurements, which can be thought of as a tracer for ambient PM2.5. For SO4(2-),
      personal-ambient associations were strong even in poorly ventilated indoor
      environments, suggesting that personal exposures to PM2.5 of ambient origin are
      strongly associated with corresponding ambient concentrations. The results also
      indicated that the contribution of indoor PM2.5 sources to personal PM2.5
      exposures was lowest when individuals spent the majority of their time in well
      ventilated indoor environments. Results also indicate that the potential for
      confounding by PM2.5 co-pollutants is limited, despite significant correlations
      among ambient pollutant concentrations. In contrast to ambient concentrations,
      PM2.5 exposures were not significantly correlated with personal exposures to
      PM2.5-10, PM2.5 of non-ambient origin, O3, NO2, and SO2. Since a confounder must
      be associated with the exposure of interest, these results provide evidence that
      the effects observed in the PM2.5 epidemiologic studies are unlikely to be due to
      confounding by the PM2.5 co-pollutants measured in this study.

PMID- 10939212
TI  - Air pollution and hospital admissions for diseases of the circulatory system in
      three U.S. metropolitan areas.
AB  - Generalized additive models were used to analyze the time series of daily
      hospital admissions for cardiovascular and cerebrovascular diseases over the
      period of 1987-1995 in three major metropolitan areas--Cook County, IL; Los
      Angeles County, CA; and Maricopa County, AZ--in the United States. In Cook and
      Maricopa Counties, admissions information was only available for the elderly
      (ages 65 and over), while in Los Angeles County, admissions information was
      available for all ages. In Cook County, daily monitoring information was
      available on PM10, CO, SO2, NO2, and O3. In Los Angeles and Maricopa Counties,
      monitoring information was available daily on the gases, and information on PM10
      was available every sixth day. In Los Angeles County, information on PM2.5 was
      also available every sixth day. In Cook and Los Angeles Counties, associations
      were found between each pollutant, with the exception of O3, and admissions for
      cardiovascular disease, with the gases showing the strongest associations. In two
      pollutant models with PM and one of the gases, the effect of the gases remained
      stable, while the effect of PM became unstable and insignificant. In Maricopa
      County, the gases, with the exception of O3, were weakly associated with hospital
      admissions for cardiovascular disease, while PM was not. In two-pollutant models
      with two of CO, SO2, and NO2, the pattern of results is heterogeneous in the
      three counties. In all three counties, only weak evidence of any association
      between air pollution and cerebrovascular admissions was found.

PMID- 10939213
TI  - The evolution of particles in the plume from a large coal-fired boiler with flue
      gas desulfurization.
AB  - Airborne measurements were made of gaseous and particulate species in the plume
      of a large coal-fired power plant after flue gas desulfurization (FGD) controls
      were installed. These measurements were compared with measurements made before
      the controls were installed. The light scattering and number and volume
      distributions of plume excess particles were determined by nephelometry and
      optical particle counting techniques. The plume impact based on optical
      techniques was much lower than that observed in earlier measurements. Indeed,
      plume excess volumes as a function of particle size were of the same magnitude as
      the variability of the background volume distribution. In situ excess plume
      scattering actually decreased with distance from the source, in contrast to pre
      FGD conditions. The upper limit for the dry rate of SO2-to-SO4(2-) conversion was
      estimated from plume excess volume measurements to be about 4% hr-1. This is
      slightly greater than the upper limit, 3.5% hr-1, estimated by earlier
      researchers, but the same as that estimated using the present technique with the
      earlier data. The cross-plume profile of volume suggests SO2-to-SO4(2-)
      conversion is highest at the plume edges. The greatest benefit of SO2 reduction
      on plume excess volume and visibility appears to occur far down-wind of the
      source.

PMID- 10939214
TI  - Is daily mortality associated specifically with fine particles? Data
      reconstruction and replication of analyses.
AB  - In 1996, Schwartz, Dockery, and Neas reported that daily mortality was more
      strongly associated with concentrations of PM2.5 than with concentrations of
      larger particles (coarse mass [CM]) in six U.S. cities ("original
      paper"/"original analyses"). Because of the public policy implications of the
      findings and the uniqueness of the concentration data, we undertook a reanalysis
      of these results. This paper presents results of the reconstruction of these data
      and replication of the original analyses using the reconstructed data. The
      original investigators provided particulate air pollution data for this paper.
      Daily weather and daily counts of total and cause-specific deaths were
      reconstructed from original public records. The reconstructed particulate air
      pollution and weather data were consistent with the summaries presented in the
      original paper. Daily counts of deaths in the reconstructed data set were lower
      than in the original paper because of restrictions on residence and place of
      death. The reconstruction process identified an administrative change in county
      codes that led to higher numbers of deaths in St. Louis. Despite these
      differences in daily counts of deaths, the estimated effects of particulate air
      pollution from the reconstructed dataset, using analytic methods as described in
      the original paper, produced combined effect estimates essentially equivalent to
      the originally published results. For example, the estimated association of a 10
      micrograms/m3 increase in 2-day mean particulate air pollution on total mortality
      was 1.3% (95% confidence interval [CI] 0.9-1.7%, t = 6.53) for PM2.5 based on the
      reconstructed dataset, compared to the originally reported association of 1.5%
      (95% CI 1.1-1.9%, t = 7.41). For coarse particles, the estimated association from
      the reconstructed dataset was 0.4% (95% CI -0.2-0.9%, t = 1.43) compared to the
      originally reported association of 0.4% (95% CI -0.1-1.0%, t = 1.48). These
      results from the reconstructed data suggest that the original results reported by
      Schwartz, Dockery, and Neas were essentially replicated.

PMID- 10939215
TI  - Hourly personal exposures to fine particles and gaseous pollutants--results from
      Baltimore, Maryland.
AB  - A study to characterize 1-hr multi-pollutant exposures was performed in
      Baltimore, MD, during the summer of 1998 and the winter of 1999, and was
      conducted over a 15-day period in each of the two seasons. Personal exposures
      were measured by a trained field technician, who wore a newly developed Roll
      Around System (RAS) to measure 1-hr PM2.5 and gaseous (CO, O3, NO2, SO2, volatile
      organic compounds [VOCs]) exposures. One-hour O3, NO2, and SO2 personal exposures
      were measured using samplers developed in our laboratory, while short-term PM2.5,
      CO, and VOCs exposures were measured using currently available monitors. All 1-hr
      multi-pollutant exposures were measured while the technician performed pre
      determined activities, beginning at 7:00 a.m. and ending at 7:00 p.m. of the same
      day. Activities were scripted to simulate activities performed by older adults
      (65+ years of age). Corresponding 1-hr ambient pollutant concentrations were
      obtained from federal or state monitoring networks. In this paper, we discuss the
      results from our study and present our descriptive analysis of the 1-hr personal
      particulate and gaseous exposure data. Personal PM2.5, O3, CO, and VOCs exposures
      showed substantial variability over the 12-hr sampling periods. Multiple pairwise
      comparison tests showed that 1-hr personal O3 exposures were significantly lower
      in indoor microenvironments as compared with outdoor microenvironments. One-hour
      personal CO exposures measured in vehicles were significantly higher than those
      measured in other microenvironments. The associations between 1-hr personal
      exposures and corresponding ambient concentrations differed by pollutant and by
      microenvironment. For example, the correlation between personal PM2.5 exposures
      and ambient concentrations was lowest (rs = 0.36, p < 0.05) in the winter for
      indoor non-residential microenvironments, and was highest (rs = 0.90, p < 0.05)
      in the winter for in-vehicle microenvironments. For O3, the correlation between
      personal exposures and ambient levels was weakest in the winter for residential
      microenvironments (rs = 0.05, p > 0.05), and was strongest in the summer for
      outdoor near-roadway microenvironments (rs = 0.91, p < 0.05).

PMID- 10939216
TI  - Characterization of indoor particle sources using continuous mass and size
      monitors.
AB  - A comprehensive indoor particle characterization study was conducted in nine
      Boston-area homes in 1998 in order to characterize sources of PM in indoor
      environments. State-of-the-art sampling methodologies were used to obtain
      continuous PM2.5 concentration and size distribution particulate data for both
      indoor and outdoor air. Study homes, five of which were sampled during two
      seasons, were monitored over week-long periods. Among other data collected during
      the extensive monitoring efforts were 24-hr elemental/organic carbon (EC/OC)
      particulate data as well as semi-continuous air exchange rates and time-activity
      information. This rich data set shows that indoor particle events tend to be
      brief, intermittent, and highly variable, thus requiring the use of continuous
      instrumentation for their characterization. In addition to dramatically
      increasing indoor PM2.5 concentrations, these data demonstrate that indoor
      particle events can significantly alter the size distribution and composition of
      indoor particles. Source event data demonstrate that the impacts of indoor
      activities are especially pronounced in the ultrafine (da < or = 0.1 micron) and
      coarse (2.5 < or = da < or = 10 microns) modes. Among the sources of ultrafine
      particles characterized in this study are indoor ozone/terpene reactions.
      Furthermore, EC/OC data suggest that organic carbon is a major constituent of
      particles emitted during indoor source events. Whether exposures to indoor
      generated particles, particularly from large short-term peak events, may be
      associated with adverse health effects will become clearer when biological
      mechanisms are better known.

PMID- 10939218
TI  - Comparison of computer simulations of total lung deposition to human subject data
      in healthy test subjects.
AB  - A mathematical model was used to predict the deposition fractions (DF) of PM
      within human lungs. Simulations using this computer model were previously
      validated with human subject data and were used as a control case. Human
      intersubject variation was accounted for by scaling the base lung morphology
      dimensions based on measured functional residual capacity (FRC) values.
      Simulations were performed for both controlled breathing (tidal volumes [VT] of
      500 and 1000 mL, respiratory times [T] from 2 to 8 sec) and spontaneous breathing
      conditions. Particle sizes ranged from 1 to 5 microns. The deposition predicted
      from the computer model compared favorably with the experimental data. For
      example, when VT = 1000 mL and T = 2 sec, the error was 1.5%. The errors were
      slightly higher for smaller tidal volumes. Because the computer model is
      deterministic (i.e., derived from first principles of physics), the model can be
      used to predict deposition fractions for a range of situations (i.e., for
      different ventilatory parameters and particle sizes) for which data are not
      available. Now that the model has been validated, it may be applied to risk
      assessment efforts to estimate the inhalation hazards of airborne pollutants.

PMID- 10939217
TI  - Validity of ambient levels of fine particles as surrogate for personal exposure
      to outdoor air pollution--results of the European EXPOLIS-EAS Study (Swiss Center
      Basel).
AB  - To evaluate the validity of fixed-site fine particle levels as exposure
      surrogates in air pollution epidemiology, we considered four indicator groups:
      (1) PM2.5 total mass concentrations, (2) sulfur and potassium for regional air
      pollution, (3) lead and bromine for traffic-related particles, and (4) calcium
      for crustal particles. Using data from the European EXPOLIS (Air Pollution
      Exposure Distribution within Adult Urban Populations in Europe) study, we
      assessed the associations between 48-hr personal exposures and home outdoor
      levels of the indicators. Furthermore, within-city variability of fine particle
      levels was evaluated. Personal exposures to PM2.5 mass were not correlated to
      corresponding home outdoor levels (n = 44, rSpearman (Sp) = 0.07). In the group
      reporting neither relevant indoor sources nor relevant activities, personal
      exposures and home outdoor levels of sulfur were highly correlated (n = 40, rSp =
      0.85). In contrast, the associations were weaker for traffic (Pb: n = 44, rSp =
      0.53; Br: n = 44, rSp = 0.21) and crustal (Ca: n = 44, rSp = 0.12) indicators.
      This contrast is consistent with spatially homogeneous regional pollution and
      higher spatial variability of traffic and crustal indicators observed in Basel,
      Switzerland. We conclude that for regional air pollution, fixed-site fine
      particle levels are valid exposure surrogates. For source-specific exposures,
      however, fixed-site data are probably not the optimal measure. Still, in air
      pollution epidemiology, ambient PM2.5 levels may be more appropriate exposure
      estimates than total personal PM2.5 exposure, since the latter reflects a mixture
      of indoor and outdoor sources.

PMID- 10939219
TI  - Risperidone and withdrawal dyskinesia.

PMID- 10939220
TI  - Risperidone in anorexia nervosa.

PMID- 10939221
TI  - Nefazodone for PTSD.

PMID- 10939222
TI  - Adolescents' experiences with ECT.

PMID- 10939223
TI  - Camptocormia in an adolescent.

PMID- 10939224
TI  - The genetics of childhood psychiatric disorders: a decade of progress.
AB  - OBJECTIVE: To review the literature over the past decade on the genetics of
      childhood neuropsychiatric disorders. METHOD: A computerized search was performed
      for articles published in the past decade, and selected papers were highlighted.
      RESULTS: The past decade of research has illuminated the complex genetics of
      early-onset mental disorders. Advances in statistical methodologies and
      laboratory-based gene-hunting techniques are laying the foundation for a deeper
      understanding of both the biological and environmental factors that contribute to
      mental illness. Researchers are on the verge of identifying and characterizing
      genetic vulnerabilities involved in common childhood psychiatric syndromes.
      CONCLUSIONS: Although the study of the genetics of childhood psychiatric
      disorders has advanced significantly over the past decade, considerable work
      remains. The identification of genes conferring vulnerability to psychiatric
      illnesses will have the potential to transform the field by providing insight
      into both biological and environmental determinants that contribute to serious
      developmental and psychiatric disorders in children and adolescents. These
      advances promise new understanding and new avenues for prevention and treatment.
      They will also present physicians and families with significant clinical and
      ethical challenges.

PMID- 10939225
TI  - Children's adjustment in conflicted marriage and divorce: a decade review of
      research.
AB  - OBJECTIVES: To review important research of the past decade in divorce, marital
      conflict, and children's adjustment and to describe newer divorce interventions.
      METHOD: Key empirical studies from 1990 to 1999 were surveyed regarding the
      impact of marital conflict, parental violence, and divorce on the psychological
      adjustment of children, adolescents, and young adults. RESULTS: Recent studies
      investigating the impact of divorce on children have found that many of the
      psychological symptoms seen in children of divorce can be accounted for in the
      years before divorce. The past decade also has seen a large increase in studies
      assessing complex variables within the marriage which profoundly affect child and
      adolescent adjustment, including marital conflict and violence and related
      parenting behaviors. This newer literature provides provocative and helpful
      information for forensic and clinical psychiatrists in their work with both
      married and divorcing families. CONCLUSIONS: While children of divorced parents,
      as a group, have more adjustment problems than do children of never-divorced
      parents, the view that divorce per se is the major cause of these symptoms must
      be reconsidered in light of newer research documenting the negative effects of
      troubled marriages on children.

PMID- 10939226
TI  - Stimulant treatment for children: a community perspective.
AB  - OBJECTIVE: To examine the use of prescribed stimulants in relation to research
      diagnoses of attention-deficit hyperactivity disorder (ADHD) in a community
      sample of children. METHOD: Data from 4 annual waves of interviews with 9- to 16
      year-olds from the Great Smoky Mountains Study were analyzed. RESULTS: Over a 4
      year period, almost three quarters of children with an unequivocal diagnosis of
      ADHD received stimulant medications. However, girls and older children with ADHD
      were less likely to receive such treatment. Most children with impairing ADHD
      symptoms not meeting full criteria for DSM-III-R ADHD did not receive stimulant
      treatment. Stimulant treatment in this group was significantly related to the
      level of symptoms reported by parents and teachers and was much more common in
      individuals who met criteria for oppositional defiant disorder. The majority of
      individuals who received stimulants were never reported by their parents to have
      any impairing ADHD symptoms. They did have higher levels of nonimpairing parent
      reported ADHD symptoms, higher levels of teacher-reported ADHD symptoms, and
      interviewer-observed ADHD behaviors, but these typically fell far below the
      threshold for a DSM-III-R diagnosis of ADHD. CONCLUSIONS: In this area of the
      Great Smoky Mountains, stimulant treatment was being used in ways substantially
      inconsistent with current diagnostic guidelines.

PMID- 10939227
TI  - Success-based, noncoercive treatment of oppositional behavior in children from
      violent homes.
AB  - OBJECTIVES: Errorless compliance training is a success-based, noncoercive
      intervention for children with severe oppositional behavior. The strategy
      involves hierarchical introduction of more demanding parental requests at a
      gradual pace that greatly reduces noncompliance and obviates the need for
      constraining consequences (e.g., time-out). In this study, this approach was
      evaluated as a treatment for severe disciplinary problems in children from
      violent homes. METHOD: Participants were 15 children (aged 3-10 years) and their
      mothers. All participants had experienced long-term family violence. Using a
      multiple-baseline design, the authors trained parents in a group format and
      conducted observations of child compliance in the home throughout the
      intervention. RESULTS: Observations indicated improvements in generalized child
      compliance that were maintained up to 6 months posttreatment. Pre-/post maternal
      reports indicated significant reductions in maternal perception of child
      noncompliance, externalizing and internalizing problems, and parenting stress.
      CONCLUSIONS: Researchers have noted a dearth of empirically supported
      interventions for children from violent homes. Errorless compliance training may
      help to fill this void, as it appears well suited to treatment of difficulties
      encountered by these youngsters and their parents.

PMID- 10939228
TI  - Commentary: issues in training parents to manage children with behavior problems.

PMID- 10939230
TI  - Gender-specific characteristics of 5-year-olds' play narratives and associations
      with behavior ratings.
AB  - OBJECTIVES: To examine the content and structure of children's play narratives in
      a large sample of 5-year-olds in order to replicate previous findings, explore
      the role of gender differences, and identify a pattern that can provide useful
      information about children's behavior. METHOD: The MacArthur Story Stem Battery
      and coding system was used to code content themes and coherence from play
      narratives of 652 twins in a nonclinical sample. To measure behavior problems,
      parents completed the Child Behavior Checklist when their children were aged 5
      and 7 years; teachers completed the Teacher's Report Form when the children were
      aged 7 years. RESULTS: Girls told more coherent narratives with less aggression
      than boys. Aggressive themes were found to correlate with behavior problems as in
      previous studies. Upon further examination, this correlation held for girls but
      not boys. Children who told repeated aggressive/incoherent narratives had more
      behavior problems than those who did not show this narrative pattern.
      CONCLUSIONS: The Story Stem methodology is useful for gaining access into the
      young child's inner world. The gender of the child, content of the story, and
      coherence of the story all provide useful information in identifying narratives
      that may indicate more risk for behavior problems.

PMID- 10939229
TI  - Nefazodone pharmacokinetics in depressed children and adolescents.
AB  - OBJECTIVE: To describe the pharmacokinetics and safety of nefazodone (NFZ) in
      depressed children and adolescents. METHOD: Depressed youths aged 7 to 17 years
      were eligible to participate. Intensive sampling for pharmacokinetic analyses of
      NFZ and 3 of its active metabolites was performed after single and multiple dose
      administration. Treatment was continued for 6 more weeks and titrated to maximize
      clinical response. RESULTS: Twenty-eight patients were enrolled. Systemic
      exposure to NFZ and 3 metabolites was generally higher in children than
      adolescents. NFZ and metabolite disposition profiles showed high intra- and
      interpatient variability. Compared to published data in adults, the half-life of
      NFZ and 2 of its metabolites appears shorter in children and adolescents. Meta
      chlorphenylpiperazine pharmacokinetic parameters were different in 5 patients
      determined to be poor metabolizers of cytochrome P450 2D6 (CYP2D6). NFZ was well
      tolerated, and administration was associated with significant reductions (p <
      .001) in depressive symptoms. CONCLUSIONS: The pharmacokinetics of NFZ in
      pediatric patients is highly variable. NFZ appears to be safe in this small,
      short-term study. Pediatric patients who are poor metabolizers of CYP2D6 do not
      appear to be at increased risk for NFZ-associated adverse events. Open-label
      treatment of NFZ is associated with reductions in depressive symptoms.

PMID- 10939231
TI  - Human figure drawings in the evaluation of severe adolescent suicidal behavior.
AB  - OBJECTIVE: To evaluate the reliability of using certain indicators derived from
      human figure drawings to distinguish between suicidal and nonsuicidal
      adolescents. METHOD: Ninety consecutive admissions to an adolescent inpatient
      unit were assessed. Thirty-nine patients were admitted because of suicidal
      behavior and 51 for other reasons. All subjects were given the Human Figure
      Drawing (HFD) test. HFD was evaluated according to the method of Pfeffer and
      Richman, and the degree of suicidal behavior was rated by the Child Suicide
      Potential Scale. RESULTS: The internal reliability was satisfactory. HFD
      indicators correlated significantly with quantitative measures of suicidal
      behavior; of these indicators specifically, overall impression of the evaluator
      enabled the prediction of suicidal behavior and the distinction between suicidal
      and nonsuicidal inpatients (p < .001). A group of graphic indicators derived from
      a discriminant analysis formed a function, which was able to identify 84.6% of
      the suicidal and 76.6% of the nonsuicidal adolescents correctly. Many of the
      items had a regressive quality. CONCLUSIONS: The HFD is an example of a simple
      projective test that may have empirical reliability. It may be useful for the
      assessment of severe suicidal behavior in adolescents.

PMID- 10939233
TI  - Social phobia and separation anxiety symptoms in community and clinical samples
      of children and adolescents.
AB  - OBJECTIVE: To examine the developmental progression and pattern of self-reported
      symptoms of social phobia (SP) and separation anxiety (SA) in community (n =
      2,384) and clinical (n = 217) samples of children and adolescents, using a cross
      sectional method. METHOD: Subjects were cross-classified by age, gender, and
      race. Using mean scores on the SP and SA subscales of the Multidimensional
      Anxiety Scale for Children, 4 categories of children were established:
      HighSP/HighSA, HighSP/LowSA, LowSP/HighSA, and LowSP/LowSA. Data were analyzed
      using a generalized logit model. RESULTS: Community sample: Preadolescents and
      females reported more symptoms of HighSP/HighSA and LowSP/HighSA than adolescents
      and males. White children reported more symptoms of HighSP/LowSA, while the
      opposite pattern was found among African-American children. Clinical sample:
      Similar to the community sample, preadolescents reported more symptoms of
      HighSP/HighSA. However, clinical males reported more symptoms of LowSP/HighSA
      than clinical females. CONCLUSIONS: In general, adolescents endorsed more
      symptoms of SP and fewer symptoms of SA than preadolescent children. Irrespective
      of age, white children endorsed more symptoms of SP and fewer symptoms of SA than
      African-American children. In the community sample, preadolescent boys endorsed
      more symptoms of SA and fewer symptoms of SP, suggesting a possible referral
      bias.

PMID- 10939232
TI  - The Service Assessment for Children and Adolescents (SACA): adult and child
      reports.
AB  - OBJECTIVE: To describe differences in parent-child responses to the Service
      Assessment for Children and Adolescents (SACA). METHOD: Studies were done at UCLA
      and Washington University based on service-using and community subjects drawn
      from community households or public school student lists, respectively. Results
      are presented for 145 adult-youth pairs in which the youth was 11 or older.
      RESULTS: The SACA adult-youth correspondence for lifetime use of any services,
      inpatient services, outpatient services, and school services ranged from fair to
      excellent (kappa = 0.43-0.86, with most at 0.61 or greater). Similarly, the SACA
      showed a good to excellent correspondence for services that had been used in the
      preceding year (kappa = 0.45-0.77, with most greater than 0.50). The parent-youth
      correspondence for use of specific service settings in the above generic
      categories ranged from poor to excellent (kappa = 0.25-0.83, with half at 0.50 or
      greater). CONCLUSIONS: The SACA has better adult-youth correspondence than any
      service use questionnaire with published data, indicating that both adult and
      youth reports are not needed for all research on mental health services. This is
      especially encouraging news for researchers working with high-risk youth
      populations, in which a parent figure is often not available.

PMID- 10939234
TI  - Sexual attitudes and associated psychiatric features among youths in a community
      sample.
AB  - OBJECTIVE: Using an epidemiological sample of adolescents, this study examined
      associations between the acceptability of potential sex partners and psychiatric
      status. METHOD: Subjects aged 14 to 17 years (N = 161) from the Columbia site of
      the National Institute of Mental Health (NIMH) Methods for the Epidemiology of
      Child and Adolescent Mental Disorders (MECA) Study were grouped according to
      their responses about the acceptability of youths their age having sex with
      partners of (1) the opposite sex, (2) neither sex, and (3) either sex. Youths
      endorsing either sex were compared with youths endorsing the other two types of
      partners according to psychiatric indicators obtained from the Diagnostic
      Interview Schedule for Children Version 2.3. RESULTS: Higher-than-expected
      proportions of male and female youths endorsed sex partners of either sex as
      potentially acceptable for peers. Youths who did so abused substances and used
      mental health services more than peers but did not differ in rates of suicidal
      ideation or attempts. Males endorsing either sex also had higher rates of mood
      disorders and, compared with males endorsing only the opposite sex, a higher
      intelligence level. CONCLUSIONS: Attitudes about the potential acceptability of
      sex partners for peers are associated with psychiatric morbidity and mental
      health service use in the respondent as well as with intelligence level in males.
      Youths who endorsed potential sex partners of either sex, especially males,
      appear to be at higher risk for multiple psychiatric problems.

PMID- 10939236
TI  - ADHD in parents.

PMID- 10939235
TI  - Case study: childhood-onset tardive dyskinesia versus choreoacanthocytosis.
AB  - A male adolescent presented with aggression, depressed mood, and severe movement
      disorder that developed at age 5 after exposure to neuroleptics. Evaluation
      revealed acanthocytes in his blood, which led to a differential diagnosis of
      tardive dyskinesia versus choreoacanthocytosis. However, this is unusually young
      age of onset for these conditions. Differential diagnosis, medication management
      of the movement disorder, and pathophysiological mechanisms in tardive dyskinesia
      and choreoacanthocytosis are discussed.

PMID- 10939237
TI  - Randomized experimental designs.

PMID- 10939238
TI  - Genetics of childhood disorders: XVII. ADHD, Part 1: The executive functions and
      ADHD.

PMID- 10939239
TI  - Conversion of solvent evaporation residues from the AB- (acetone-butanol)
      bioprocess into bacterial cells accumulating thermoplastic polyesters.
AB  - In a bioconversion study based on utilisation of by-products from the AB-
      (acetone-butanol) bioprocess a new isolated gram-negative solvent tolerant
      bacterium was used to convert the AB process residue after removal of the major
      part of the solvents. The bacterium identified as a representative of the genus
      Alcaligenes (designated as Alcaligenes sp. G) was capable of growth up to optical
      densities ranging from 8 to 20 and simultaneously of polyhydroxyalkanoate- (PHA
      )accumulation up to 40% per dry weight. A standardised medium based on AB by
      products containing 7 g/l of butyrate and 5 g/l of acetate at pH 7.5 was used in
      our studies for bioconversion into PHAs. Concentrations of 1-butanol, which is
      known for its membrane damaging properties in micro-organisms, were tolerated in
      the AB by-products medium up to 4 g/l without significant inhibition of cellular
      growth. No inhibition of growth was observed, when the medium was adjusted to 40
      g/l butyrate. Due to the toxicity of the remaining 1-butanol maintenance of
      sterility is of no high priority during the process. The use of acetate and
      butyrate from an AB process is expected to provide a higher return-on-investment
      than the combustion of biogas to help meet energy demands.

PMID- 10939240
TI  - Phylogenetic analyses of the constituents of Type III protein secretion systems.
AB  - Multicomponent Type III protein secretion systems transfer gram-negative
      bacterial virulence factors directly from the bacterial cytoplasm to the
      cytoplasm of a host eukaryotic cell in a process that may involve a single energy
      coupled step. Extensive evidence supports the conclusion that the genetic
      apparatuses that encode these systems have been acquired independently by
      different gram-negative bacteria, presumably by lateral transfer. In this paper
      we conduct phylogenetic analyses of currently sequenced constituents of these
      systems and their homologues. The results reveal the relative relatedness of
      these systems and show that they evolved with little or no exchange of
      constituents between systems. This fact suggests that horizontal transmission of
      the genes encoding these systems always occurred as a unit without the formation
      of hybrid gene clusters. Moreover, homologous flagellar proteins show
      phylogenetic clustering that suggests that the flagellar systems and Type III
      protein secretory systems diverged from each other following very early
      duplication of a gene cluster sharing many (but not all) genes. Phylogenies of
      most or all of the flagellar proteins follow those of the source organisms with
      little or no lateral gene transfer suggesting that homologous flagellar proteins
      are true orthologues. We suggest that the flagellar apparatus was the
      evolutionary precursor of Type III protein secretion systems.

PMID- 10939241
TI  - Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction.
AB  - Living organisms are composed of macromolecules made of hydrogen, carbon,
      nitrogen, oxygen, phosphorus and sulfur. Much work has been devoted to the
      metabolism of the first five elements, but much remains to be understood about
      sulfur metabolism. We review here the situation in Escherichia coli and related
      bacteria, where more than one hundred genes involved in sulfur metabolism have
      already been discovered in this organism. Examination of the genome suggests that
      many more will be found, especially genes involved in regulation, scavenging of
      sulfur containing molecules and synthesis of coenzymes or prosthetic groups.
      Furthermore, the involvement of methionine as the universal start of proteins as
      well as that of its derivative S-adenosylmethionine in a vast variety of cell
      processes argue in favour of a major importance of sulfur metabolism in all
      organisms.

PMID- 10939242
TI  - Bacterial twin-arginine signal peptide-dependent protein translocation pathway:
      evolution and mechanism.
AB  - The recently identified bacterial Tat pathway is capable of exporting proteins
      with a peculiar twin-arginine signal peptide in folded conformation independently
      of the Sec machinery. It is structurally and mechanistically similar to the delta
      pH-dependent pathway used for importing chloroplast proteins into the thylakoid.
      The tat genes are not ubiquitously present and are absent from half of the
      completely sequenced bacterial genomes. The presence of the tat genes seems to
      correlate with genome size and with the presence of important enzymes with a twin
      arginine signal peptide. A minimal Tat system requires a copy of tatA and a copy
      of tatC. The composition and gene order of a tat locus are generally conserved
      within the same taxonomy group but vary considerably to other groups, which would
      exclude an acquisition of the Tat system by recent horizontal gene transfer. The
      tat genes are also found in the genomes of chloroplasts and plant mitochondria
      but are absent from animal mitochondrial genomes. The topology of evolution trees
      suggests a bacterial origin of the Tat system. In general, the twin-arginine
      signal peptide is capable of targeting any passenger protein to the Tat pathway.
      However, a structural signal carried by the mature part of a passenger protein
      can override targeting information in a signal peptide under certain
      circumstances. Tat systems show a substrate-Tat component specificity and a
      species specificity. The pore size of the Tat channel is estimated as being
      between 5 and 9 nm. Operational models of the Tat system are proposed.

PMID- 10939243
TI  - The ATP-cone: an evolutionarily mobile, ATP-binding regulatory domain.

PMID- 10939244
TI  - A novel ubiquitous family of putative efflux transporters.
AB  - We describe a novel family of putative efflux transporters (PET) found in
      bacteria, yeast and plants. None of the members of the PET family has been
      functionally characterized. The bacterial and yeast proteins display a duplicated
      internal repeat element consisting of an N-terminal hydrophobic sequence of about
      170 residues, exhibiting six putative transmembrane alpha-helical spanners
      (TMSs), followed by a large (230 residue), C-terminal, hydrophilic, cytoplasmic
      domain. The plant proteins exhibit only one such unit, but they have a larger C
      terminal cytoplasmic domain. Arabidopsis thaliana encodes at least seven
      paralogues of the PET family. The gram-negative bacterial proteins are sometimes
      encoded by genes that are found in operons that also contain genes that encode
      membrane fusion proteins. This fact strongly suggests that PET family proteins
      are efflux pumps. The sequence, topological and phylogenetic characteristics of
      these proteins as well as the operonic structures of their encoded genes when
      relevant are described.

PMID- 10939245
TI  - Characterization of OpuA, a glycine-betaine uptake system of Lactococcus lactis.
AB  - A Lactococcus lactis glycine-betaine transport system was identified by
      functional complementation of an Escherichia coli proP proU mutant with a gene
      library from L. lactis sbsp. cremoris. The cloned locus forms an operon highly
      homologous to opuA, encoding a glycine-betaine uptake system of Bacillus
      subtilis. Disruption of opuA in L. lactis abolished protection by glycine-betaine
      against elevated osmolarity. OpuA belongs to the so-called "ABC transporters"
      family, which comprise an extracellularly localized substrate-binding protein. In
      B. subtilis OpuA system, this binding protein is a lipoprotein, attached to the
      external face of the cytoplasmic membrane by its lipidic moiety. In contrast, in
      the L. lactis opuA operon, and in other gram-positive homologues as well, a
      fusion between the gene encoding the integral membrane protein and the substrate
      binding protein components gave rise to a hybrid protein presumably attaching the
      substrate-binding protein to the surface of the cell via its covalent link to the
      integral membrane component. Mapping of L. lactis opuA transcription start
      identified one mRNA, more abundant in cells grown at elevated osmolarity.
      Construction of an opuA-gusA fusion confirmed that opuA transcription is directed
      by a promoter osmotically inducible in L. lactis. When recombined upstream from a
      lac transcriptional fusion in the chromosome of E. coli, the opuA promoter
      appeared as very strong, and only poorly stimulated by elevated osmotic pressure,
      suggesting the existence of a specific machinery involved in the osmotic signal
      transduction in L. lactis.

PMID- 10939246
TI  - Strong hybrid promoters and integrative expression/secretion vectors for quasi
      constitutive expression of heterologous proteins in the yeast Yarrowia
      lipolytica.
AB  - The industrial yeast Yarrowia lipolytica secretes high amounts of an alkaline
      extracellular protease encoded by the XPR2 gene. The industrial use of the XPR2
      promoter was however hindered by its complex regulation. We designed hybrid
      promoters, based on tandem copies of the XPR2 promoter UAS1 region. In contrast
      to native XPR2 promoter, these hybrid promoters were not repressed by the
      preferred carbon and nitrogen sources, nor by acidic conditions, and they did not
      require the presence of peptones in the culture medium. They exhibited a strong
      quasi-constitutive activity, similar when carried on either integrative or
      replicative plasmids. We used these hybrid promoters to direct the production of
      bovine prochymosin, using XPR2 secretion signals. The production of active
      chymosin was several fold higher than with previously available Y. lipolytica
      promoters (up to 160 mg/l). Integrative vectors based on the hybrid promoters,
      allowing the easy insertion of a heterologous gene and its expression or
      expression/secretion in Y. lipolytica, were designed. We also designed new Y.
      lipolytica recipient strains with good secreting abilities, able to grow on
      sucrose, and devoid of extracellular proteases. These new tools will add to the
      interest of Y. lipolytica as a host for heterologous protein production.

PMID- 10939247
TI  - Recombinant acylheptapeptide lichenysin: high level of production by Bacillus
      subtilis cells.
AB  - Peptide synthetases are multi-domain proteins that catalyze the assembly, from
      amino acids and amino acid derivatives, of peptides and lipopeptides, some of
      which exhibit activities (pharmaceutical, surfactant, etc.) of considerable
      biotechnological importance. Although there is substantial interest in the
      generation of greater peptide diversity, in order to create new
      biotechnologically interesting products, attempts reported so far to exchange
      amino acid-activating minimal modules between enzymes have only yielded hybrid
      catalysts with poor activities. We report here the replacement of an entire
      first, L-Glu-, and fifth, L-Asp-incorporating modules of surfactin synthetase, to
      create a fully active hybrid enzyme that forms a novel peptide in high yields.
      Whole encoding regions of lichenysin A synthetase modules were introduced into
      surfactin biosynthesis operon between His140/His1185 of SrfAA and His1183/His2226
      of SrfAB, the amino acid residues of a proposed active-site motif (HHXXXDG) of
      the condensation domains which is involved in the catalysis of nonribosomal
      peptide bond formation (Stachelhaus et al., 1998). When the lipopeptides produced
      by the recombinant Bacillus subtilis strains were purified and characterized,
      they appeared to be expressed approximately at the same level of the wild type
      surfactin and to be identical by their fatty acid profiles. We thereby
      demonstrate the utility of whole module swapping for designing novel peptides,
      for creating peptide diversity, and for redesigning existing peptides produced in
      performant production strains in high yields to correspond to desired peptides
      produced in low yields, or from strains unsuitable for production purposes.

PMID- 10939248
TI  - Genetic characterization of gram-positive homologs of the XerCD site-specific
      recombinases.
AB  - Homologs of the XerCD enzymes, which in Escherichia coli have been shown to be
      responsible for resolving chromosomal multimers prior to chromosome segregation,
      were identified in the genomes of Staphylococcus aureus and Streptococcus
      pneumoniae. Phylogenetic and conservation pattern analysis suggests that the S.
      aureus gene products are orthologs of XerC and D. A S. aureus xerC null mutant
      displayed in vitro characteristics consistent with the segregation defect
      reported for E. coli xer mutants, and was found to be attenuated in a murine
      infection model. Strikingly, the S. aureus xerD gene appears to be absolutely
      required for viability, and may therefore be the first example of an essential
      gene of the lambda integrase family. In contrast, phylogenetic and conservation
      pattern analysis show that the S. pneumoniae gene products are more closely
      related to phage integrases than to XerCD. S. pneumoniae xer1, 2 and 3 null
      mutants were each found to be attenuated in a murine infection model, suggesting
      that they may control processes which affect virulence.

PMID- 10939249
TI  - DNA binding of wild type RegA protein and its differential effect on the
      expression of pigment binding proteins in Rhodobacter capsulatus.
AB  - The transcription of genes encoding pigment binding proteins in the facultative
      photosynthetic bacterium Rhodobacter capsulatus is regulated in response to
      oxygen partial pressure. Previous results identified RegA and RegB as members of
      a two component system involved in oxygen dependent synthesis of the
      photosynthetic apparatus. Here we demonstrate that RegA differentially controls
      the transcription of the puf and pucoperons which encode proteins of the LHI and
      LHII antenna complexes, respectively. In a regA mutant strain the level of puf
      specific mRNA reaches about 30% of the wild type levels and transcription is
      still responsive to oxygen tension. In contrast, the level of puc specific mRNA
      is very low and is no longer oxygen regulated. RegA binds to DNA sequences
      upstream of both the puf and puc operons, although with different affinities. We
      provide experimental evidence that a putative helix-turn-helix motif in the C
      terminal region of RegA is responsible for its specific binding to the puf and
      puc promoter regions. In contrast to many other response regulators, the affinity
      of RegA for the target DNA is only slightly modified by phosphorylation.

PMID- 10939250
TI  - Regulation of sigma S degradation in Salmonella enterica var typhimurium: in vivo
      interactions between sigma S, the response regulator MviA(RssB) and ClpX.
AB  - The alternate sigma factor sigmaS plays an important role in the survival of
      Salmonella typhimurium following sudden encounters with a variety of stress
      conditions. The level of sigmaS is very low in rapidly growing cells but
      dramatically increases as those cells encounter environmental stress or enter
      into stationary phase. This increase is due in large measure to the stabilization
      of sigmaS protein against degradation by the ClpXP protease. The MviA protein,
      also known as RssB or SprE in Escherichia coli, is a putative member of a two
      component signal transduction system that plays a central role in facilitating
      sigmaS degradation by ClpXP. In contrast to most two-component systems, MviA does
      not appear to regulate gene expression but is believed to interact directly with
      sigmaS and somehow facilitate degradation. We now provide evidence that
      MviA(RssB) directly interacts both with sigmaS and ClpX in vivo, presumably
      enabling presentation of sigmaS to the ClpP protease. Interactions were
      demonstrated using a bacterial two-hybrid system in which sigmaS, MviA, and ClpX
      were fused to separate moieties of Bordetella pertussis CyaA (adenylate cyclase).
      Paired hybrid plasmids containing Cya'-MviA/RpoS-'Cya or Cya'-MviA/ClpX-'Cya
      successfully reconstituted adenylate cyclase activity in both S. typhimurium and
      E. coli. However, no direct interactions were detected between ClpX and RpoS. A
      second series of experiments has indicated that the interaction between MviA and
      sigmaS requires the N-terminus but not the C-terminus of MviA. Cellular levels of
      MviA appear to be very low in the cell based on lacZ fusion, Western blot and
      Northern blot analyses suggesting a catalytic role for MviA in sigmaS
      degradation. Mutagenesis of MviA residue D58, a canonical residue subject to
      phosphorylation in many two-component systems, decreased the ability of MviA to
      facilitate sigmaS turnover in vivo confirming that phosphorylation of MviA
      increases MviA activity.

PMID- 10939251
TI  - Nod factors of Rhizobium leguminosarum bv. viciae and their fucosylated
      derivatives stimulate a nod factor cleaving activity in pea roots and are
      hydrolyzed in vitro by plant chitinases at different rates.
AB  - Nod factors (NFs) are rhizobial lipo-chitooligosaccharide signals that trigger
      root nodule development in legumes. Modifications of NF structures influence
      their biological activity and affect their degradation by plant chitinases.
      Nodulation of certain pea cultivars by Rhizobium leguminosarum bv. viciae
      requires modification of NFs at the reducing end by either an O-acetyl or a
      fucosyl group. Fucosylated NFs were produced by an in vitro reaction with NodZ
      fucosyltransferase and purified. Their biological activity on pea was tested by
      measuring their capacity to stimulate the activity of a hydrolase that cleaves
      NFs. Nonmodified and fucosylated NFs displayed this activity at nano- to
      picomolar concentrations, while a sulfated NF from Sinorhizobium meliloti was
      inactive. In an additional series of experiments, the stability of non-modified
      and fucosylated NFs in the presence of purified tobacco chitinases was compared.
      The presence of the fucosyl group affected the degradation rates and the
      accessibility of specific cleavage sites on the chitooligosaccharide backbone.
      These results suggest that the fucosyl group in NFs also weakens the interaction
      of NFs with certain chitinases or chitinase-related proteins in pea roots.

PMID- 10939252
TI  - Growth temperature regulation of host-specific modifications of rhizobial lipo
      chitin oligosaccharides: the function of nodX is temperature regulated.
AB  - Lipo-chitin oligosaccharides (LCOs) are usually produced and isolated for
      structural analysis from bacteria cultured under laboratory rather than field
      conditions. We have studied the influence of bacterial growth temperature on the
      LCO structures produced by different Rhizobium leguminosarum strains, using thin
      layer chromatographic, high-performance liquid chromatographic, and mass
      spectrometric analyses. Wild-type R. leguminosarum bv. viciae A1 was shown to
      produce larger relative amounts of nodX-mediated, acetylated LCOs at 12 degrees C
      than at 28 degrees C, indicating that the activity of nodX (a gene encoding an
      LCO O-acetyl transferase) is temperature dependent. Interestingly, symbiotic
      resistance genes sym1 and sym2 found in primitive pea cultivars are also
      temperature sensitive, only being active at low temperatures, at which they block
      nodulation by R. leguminosarum bv. viciae strains lacking nodX. We therefore
      propose that the gene-for-gene relationship between plant and bacterium has a
      temperature-sensitive mechanism as an adaptation to environmental conditions. An
      R. leguminosarum bv. trifolii strain was also shown to produce larger relative
      amounts of nodX-mediated, acetylated LCOs at 12 degrees C than at 28 degrees C.
      The major components synthesized by the two strains are produced at both
      temperatures but in different relative amounts, while some minor components are
      only produced at one of the two temperatures.

PMID- 10939253
TI  - Phosphoproteins involved in the signal transduction of cryptogein, an elicitor of
      defense reactions in tobacco.
AB  - We previously reported that the signal transduction of cryptogein, an elicitor of
      defense reactions in Nicotiana tabacum cells, involves upstream protein
      phosphorylation. In the present study, induction of these early physiological
      events was further investigated with inhibitors of protein phosphatase (PP),
      okadaic acid, and calyculin A. Calyculin A mimicked the effects of cryptogein,
      inducing an influx of calcium, an extracellular alkalinization, and the
      production of active oxygen species (AOS), suggesting that during cryptogein
      signal transduction the balance between specific protein kinase (PK) and PP
      activities was modified. To identify the phosphorylated proteins that could be
      involved early in the elicitor signaling pathway, we analyzed by 2-D
      electrophoresis the in vivo phosphorylation status of proteins after cryptogein,
      staurosporine, and calyculin A treatments of tobacco cells (5 min). Of about 100
      phospho-labeled polypeptides, 19 showed increased 32P incorporation after 5 min
      of cryptogein treatment. Phosphorylation of 12 of the 19 polypeptides depended
      upon calcium influx. Staurosporine inhibited the phosphorylations induced by
      cryptogein whereas calyculin A activated the phosphorylation of 18 of these
      polypeptides. This study highlighted the role of PKs and/or constitutive active
      PPs whose activation and inhibition, respectively, resulted in an increased
      phosphorylation of proteins that may be involved in cryptogein signal
      transduction. Identification of the phosphoproteins is in progress and will
      increase our knowledge of signal transduction pathways implicated in plant
      defense responses.

PMID- 10939255
TI  - Identification and characterization of a hexapeptide with activity against
      phytopathogenic fungi that cause postharvest decay in fruits.
AB  - A hexapeptide of amino acid sequence Ac-Arg-Lys-Thr-Trp-Phe-Trp-NH2 was
      demonstrated to have antimicrobial activity against selected phytopathogenic
      fungi that cause postharvest decay in fruits. The peptide synthesized with either
      all D- or all L-amino acids inhibited the in vitro growth of strains of
      Penicilium italicum, P. digitatum, and Botrytis cinerea, with MICs of 60 to 80
      microM and 50% inhibitory concentration (IC50) of 30 to 40 microM. The inhibitory
      activity of the peptide was both sequence- and fungus-specific since (i) sequence
      related peptides lacked activity (including one with five residues identical to
      the active sequence), (ii) other filamentous fungi (including some that belong to
      the genus Penicllium) were insensitive to the peptide's antifungal action, and
      (iii) the peptide did not inhibit the growth of several yeast and bacterial
      strains assayed. Experiments on P. digitatum identified conidial germination as
      particularly sensitive to inhibition although mycelial growth was also affected.
      Our findings suggest that the inhibitory effect is initially driven by the
      electrostatic interaction of the peptide with fungal components. The antifungal
      peptide retarded the blue and green mold diseases of citrus fruits and the gray
      mold of tomato fruits under controlled inoculation conditions, thus providing
      evidence for the feasibility of using very short peptides in plant protection.
      This and previous studies with related peptides indicate some degree of peptide
      amino acid sequence and structure conservation associated with the antimicrobial
      activity, and suggest a general sequence layout for short antifungal peptides,
      consisting of one or two positively charged residues combined with aromatic amino
      acid residues.

PMID- 10939254
TI  - An efficient cDNA-AFLP-based strategy for the identification of putative
      pathogenicity factors from the potato cyst nematode Globodera rostochiensis.
AB  - A new strategy has been designed to identify putative pathogenicity factors from
      the dorsal or subventral esophageal glands of the potato cyst nematode Globodera
      rostochiensis. Three independent criteria were used for selection. First, genes
      of interest should predominantly be expressed in infective second-stage
      juveniles, and not, or to a far lesser extent, in younger developmental stages.
      For this, gene expression profiles from five different developmental stages were
      generated with cDNA-AFLP (amplified fragment length polymorphism). Secondly, the
      mRNA corresponding to such a putative pathogenicity factor should predominantly
      be present in the esophageal glands of pre-parasitic juveniles. This was checked
      by in situ hybridization. As a third criterion, these proteinaceous factors
      should be preceded by a signal peptide for secretion. Expression profiles of more
      than 4,000 genes were generated and three up-regulated, dorsal gland-specific
      proteins preceded by signal peptide for secretion were identified. No dorsal
      gland genes have been cloned before from plant-parasitic nematodes. The partial
      sequence of these three factors, A4, A18, and A41, showed no significant homology
      to any known gene. Their presence in the dorsal glands of infective juveniles
      suggests that these proteins could be involved in feeding cell initiation, and
      not in migration in the plant root or in protection against plant defense
      responses. Finally, the applicability of this new strategy in other plant-microbe
      interactions is discussed.

PMID- 10939256
TI  - Inhibition of fungal and bacterial plant pathogens by synthetic peptides: in
      vitro growth inhibition, interaction between peptides and inhibition of disease
      progression.
AB  - Four synthetic cationic peptides, pep6, pep7, pep11 and pep20, were tested alone
      and in combinations for their antimicrobial activities against economically
      important plant pathogenic fungi (Phytophthora infestans and Alternaria solani)
      and bacteria (Erwinia carotovora subsp. carotovora and E. carotovora subsp.
      atroseptica). In in vitro studies, P. infestans and A. solani were inhibited by
      all four peptides, while E. carotovora subsp. carotovora and E. carotovora subsp.
      atroseptica were inhibited only by pep11 and pep20. All peptides completely
      inhibited P. infestans and A. solani on potato leaves and P. infestans on tubers
      at concentrations comparable to the in vitro IC50 (effective concentration for
      50% growth inhibition) values, suggesting that these peptides are more potent in
      preventing infection than in inhibiting hyphal growth in vitro. Microscopic
      observations of P. infestans and A. solani when treated with these peptides
      revealed hyphal anomalies. In tuber-infectivity assays, pep11 and pep20 reduced
      bacterial softrot symptoms by 50% at 2.0 to 2.30 microM and by 100% at 20 microM.
      In assays involving two-way combinations of these peptides, growth inhibitions of
      fungi and bacteria by the combinations were no more than the sum of growth
      inhibitions by each peptide when used alone, indicating that they act additively.
      pep11 and pep20 are not phytotoxic to potato plants at 200 microM. With strong
      and broad-spectrum antimicrobial activities of pep11 and pep20 against fungi and
      bacteria, and with no antagonistic activities, the expression of these peptides
      in transgenic potato plants could lead to enhanced disease resistance against
      these pathogens.

PMID- 10939257
TI  - Induced expression of sarcotoxin IA enhanced host resistance against both
      bacterial and fungal pathogens in transgenic tobacco.
AB  - We demonstrate here that induced expression of sarcotoxin IA, a bactericidal
      peptide from Sarcophaga peregrina, enhanced the resistance of transgenic tobacco
      plants to both bacterial and fungal pathogens. The peptide was produced with a
      modified PR1a promoter, which is further activated by salicylic acid treatment
      and necrotic lesion formation by pathogen infection. Host resistance to infection
      of bacteria Erwinia carotovora subsp. carotovora and Pseudomonas syringae pv.
      tabaci was shown to be dependent on the amounts of sarcotoxin IA expressed. Since
      we found antifungal activity of the peptide in vitro, transgenic seedlings were
      also inoculated with fungal pathogens Rhizoctonia solani and Pythium
      aphanidermatum. Transgenic plants expressing higher levels of sarcotoxin were
      able to withstand fungal infection and remained healthy even after 4 weeks, while
      control plants were dead by fungal infection after 2 weeks.

PMID- 10939258
TI  - Characterizing rice lesion mimic mutants and identifying a mutant with broad
      spectrum resistance to rice blast and bacterial blight.
AB  - Many plant mutants develop spontaneous lesions that resemble disease symptoms in
      the absence of pathogen attack. In several pathosystems, lesion mimic mutations
      have been shown to be involved in programmed cell death, which in some instances
      leads to enhanced disease resistance to multiple pathogens. We investigated the
      relationship between spontaneous cell death and disease resistance in rice with
      nine mutants with a range of lesion mimic phenotypes. All nine mutations are
      controlled by recessive genes and some of these mutants have stunted growth and
      other abnormal characteristics. The lesion mimics that appeared on the leaves of
      these mutants were caused by cell death as measured by trypan blue staining.
      Activation of six defense-related genes was observed in most of the mutants when
      the mimic lesions developed. Four mutants exhibited significant enhanced
      resistance to rice blast. One of the mutants, spl11, confers non-race-specific
      resistance not only to blast but also to bacterial blight. The level of
      resistance in the spl11 mutant to the two pathogens correlates with the defense
      related gene expression and lesion development on the leaves. The results suggest
      that some lesion mimic mutations in rice may be involved in disease resistance,
      and cloning of these genes may provide a clue to developing broad-spectrum
      resistance to diverse pathogens.

PMID- 10939259
TI  - Positive and negative regulation of salicylic acid-dependent cell death and
      pathogen resistance in Arabidopsis lsd6 and ssi1 mutants.
AB  - Salicylic acid (SA) is a key defense molecule in higher plants that is required
      for resistance to diverse pathogens. A number of mutants of Arabidopsis with
      elevated resistance to pathogens and constitutive activation of defense-related
      genes and cell death have been shown to require SA for all of their phenotypes.
      These mutants potentially identify interesting regulatory genes that control
      diverse SA responses. When dominant mutations confer SA-dependent phenotypes, it
      is important to know the genetic basis of dominance in order to draw conclusions
      on the possible mechanisms of action of the genes identified. Here I characterize
      the basis of the dominant phenotypes conferred by the ssi1 and lsd6 mutations. I
      show that ssi1 is haploinsufficient, while lsd6 is a gain-of-function mutation.
      Thus, SA-dependent responses are under both negative and positive regulation.

PMID- 10939260
TI  - External pH: an environmental signal that helps to rationalize pel gene
      duplication in Erwinia chrysanthemi.
AB  - The phytopathogenic bacterium Erwinia chrysanthemi produces five major pectate
      lyases that are key virulence factors in soft-rot disease development. Using
      transcriptional fusions, we studied the regulation of pelA, pelD, and pelE gene
      expression as a function of variation of the external pH. pelA and pelD were
      expressed when bacteria were grown in an acidic medium while pelE was transcribed
      only in basic medium. Using phenol red, we observed that, in chicory leaves, pH
      value of infected tissue varies from acidic to basic. Taken together, these
      findings are discussed in the context of a model unifying both catalysis and
      regulation to account for pel gene evolution. In particular, we propose that the
      three isoenzymes are produced sequentially during the infection process.

PMID- 10939261
TI  - Expression of pectate lyase from Colletotrichum gloesosporioides in C. magna
      promotes pathogenicity.
AB  - To test the contribution of pectate lyase (PL) to promoting fungal pathogenicity,
      a pectate lyase gene (pel) from the avocado pathogen Colletotrichum
      gloeosporioides, isolate Cg-14, was expressed in C. magna isolate L-2.5, a
      pathogen of cucurbits that causes minor symptoms in watermelon seedlings and
      avocado fruits. Isolate L-2.5 was transformed with pPCPH-1 containing hph-B as a
      selectable marker and the 4.1-kb genomic pel clone. Southern hybridization, with
      the 4.1-kb genomic pel clone or 2.13-kb hph-B cassette as probes, detected
      integration of pel in transformed C. magna isolates Cm-PL-3 and Cm-PL-10. Western
      blot (immunoblot) analysis with antibodies against Cg-14 PL detected a single PL
      secreted by L-2.5 at a molecular mass of 41.5 kDa, whereas the PL of C.
      gloeosporioides had a molecular mass of 39 kDa. When PL activity was measured 4
      days after inoculation in pectolytic enzyme-inducing media (PEIM), transformed
      isolates Cm-PL-3 and Cm-PL-10 showed additive PL activity relative to both Cg-14
      and L-2.5. Transformed isolates also showed additive maceration capabilities on
      avocado pericarp relative to the wild-type C. magna alone, but did not reach the
      maceration ability of C. gloeosporioides. However, more severe maceration and
      damping off developed in watermelon seedlings inoculated with the transformed
      isolates compared with the two wild-type isolates, which showed no symptom
      development on these seedlings during the same period. Results clearly show the
      contribution of a single pel to the pathogenic abilities of C. magna and suggest
      that PL is a pathogenicity factor required for the penetration and colonization
      of Colletotrichum species.

PMID- 10939262
TI  - Insertion of the LINE retrotransposon MGL causes a conidiophore pattern mutation
      in Magnaporthe grisea.
AB  - We obtained three Magnaporthe grisea morphological mutants that had the LINE
      transposon MGL inserted into the ACR1 locus. Sequence analysis revealed that ACR1
      is homologous to medA, a developmental regulator of Aspergillus nidulans
      conidiation. These results demonstrated that MGL elements could transpose and
      cause insertional mutagenesis in M. grisea.

PMID- 10939263
TI  - cDNA-AFLP display for the isolation of Peronospora parasitica genes expressed
      during infection in Arabidopsis thaliana.
AB  - To identify genes from the obligatory biotrophic oomycete Peronospora parasitica
      that are expressed during infection in Arabidopsis thaliana we employed cDNA
      amplified fragment length polymorphism (AFLP) display. cDNA-AFLP fragments from
      infected and non-infected leaves were separated in parallel by gel
      electrophoresis and displayed by autoradiography. Most differential gene
      fragments were derived from P. parasitica.

PMID- 10939264
TI  - Summary report on the ILSI Europe session on Microbiological Risk Assessment held
      on Thursday 16th September 1999 at Veldhoven, Netherlands during Foodmicro '99 at
      the 17th international conference of the International Committee on Food
      Microbiology and Hygiene.

PMID- 10939265
TI  - Hazard identification and exposure assessment for microbial food safety risk
      assessment.
AB  - The four cornerstones of microbial food safety risk assessment are hazard
      identification, exposure assessment, hazard characterization, and risk
      characterization. These steps represent a systematic process for identifying
      adverse consequences and their associated probabilities arising from consumption
      of foods that may be contaminated with microbial pathogens and/or microbial
      toxins. This paper presents a discussion of the first two steps: hazard
      identification and exposure assessment, and considerations for different
      approaches that can be used to analyze the relevant information.

PMID- 10939266
TI  - Microbial risk assessment: dose-response relations and risk characterization.
AB  - Characterizations of the risks associated with foodborne pathogens are dependent
      on the availability of information on the population's exposure to the biological
      agents. However, by itself, exposure data are insufficient to assess the public
      health impact of pathogenic microorganisms. This requires the availability of
      effective dose-response models. Successful development of models that describe
      dose-response relations for enteric pathogens is dependent on a sound
      understanding of the mechanisms of pathogenicity associated with individual
      pathogens. This includes knowledge of how the various pathogen, host, and food
      matrix factors influence pathogenicity. Currently, a group of sigmoidal
      mathematical equations are used to empirically describe dose-response relations.
      While these have proven to be highly useful, advances in microbial food safety
      risk assessment will likely require the development of mechanistic models that
      more effectively consider the range of factors that influence the frequency and
      severity of foodborne infections in a population.

PMID- 10939267
TI  - Microbiological risk assessment: a new approach to food safety control.
AB  - The food industry is continually looking to be innovative in the development and
      production of food. New techniques are also being employed to distribute the
      food, and even the way the consumer treats the food before consumption has
      changed dramatically over recent years, for example, with the development of
      microwavable meals. These changes can lead to differences in the pathogens
      encountered and the general level of immunity in the population. This in turn
      puts increased emphasis on food producers to know and understand more about the
      pathogens likely to occur in the products they are making and their origin. To
      help food manufacturers tackle this consistently, Microbiological Risk Assessment
      (MRA) is being applied as a systematic tool to allow effective decisions to be
      made to reduce the impact of pathogens on health.

PMID- 10939268
TI  - Quantitative risk assessment for Listeria monocytogenes in smoked or gravad
      salmon and rainbow trout in Sweden.
AB  - The objective of the present work was to develop a quantitative risk assessment
      model in which the exposure and risk of acquiring listeriosis from consumption of
      packaged smoked or gravad salmon and rainbow trout were estimated. An Excel
      spreadsheet model was constructed in which variables were represented by
      distributions based on surveys of L. monocytogenes in these food products, and on
      demographic and consumption data. Growth or inactivation was not included in the
      model. The model was run through Monte Carlo simulations using the @Risk software
      (Palisade Corporation). The probability of illness per serving was calculated
      using two dose-response models from the literature. The first was an exponential
      model in which the species specific constant R, that helps define the dose
      response curve, previously has been estimated to be 1.18 x 10(-10) based on
      German data (GR). In this study, R was estimated to 5.6 x 10(-10) based on
      Swedish data. The second model was a flexible Weibull-Gamma model (WG), with
      different coefficients for high- and low-risk groups. The exponential model (GR),
      although conservative and generally overestimating the risk, still predicted a
      lower probability of illness than the WG-model. The estimated mean risk per
      serving was 2.8 x 10(-5) (GR, high-risk group), 2.0 x 10(-3) (WG, low-risk group)
      and 0.016 (WG, high-risk group), respectively. The average number of reported
      listeriosis cases in Sweden is 37 per year. In comparison, the mean number of
      annual cases predicted by the risk assessment model was 168 (range 47 to 2800,
      GR, high-risk group), and 95 000 (range 34 000 to 1.6 x 10(6), WG high-risk
      group), respectively. If 1 to 10% (uniform distribution) of strains, instead of
      all, were considered virulent, the mean number of predicted cases would decrease
      to nine (GR) and 5200 (WG), respectively. The mean annual cumulative individual
      risk in the high-risk group based on a monthly exposure was estimated to be 4.0 x
      10(-4) (range 8.0 x 10(-8) to 5.4 x 10(-3), GR). This risk increased to 1.5 x 10(
      3) (range 1.7 x 10(-5) to 9.2 x 10(-3), GR) based on a weekly exposure. The risk
      assessment model was most sensitive to the input distribution describing the
      level of contamination and to a lesser degree on the prevalence of L.
      monocytogenes, the proportion of virulent strains, and serving sizes. A lack of
      data on the prevalence and concentration of L. monocytogenes in these products,
      dose-response data and quantitative information on the proportion of virulent
      strains were identified.

PMID- 10939269
TI  - Comparison of microbiological risk assessment studies published.
AB  - The FAO/WHO risk analysis framework and principles are in the process of being
      implemented in different national and international settings. The importance of a
      further development of international co-operation based upon agreed principles in
      this area is stressed in the Codex Alimentarius system, as well as under the
      WTO/SPS agreements. Key input in this context will come from the presentation of
      formalised microbiological risk assessments. The number of peer-review published
      microbiological risk assessments is low and the format is still variable. This
      paper presents a comparison of selected risk assessments in the microbiological
      area, and suggests a number of lessons to be learned from these.

PMID- 10939270
TI  - Biological variability and exposure assessment.
AB  - Predictive models are now commonly used for exposure assessment, with growth
      parameters defined for each microbial species. In this study, we tried to take
      into account microbial growth variability among strains of a single species.
      Bacillus cereus in pasteurized milk was chosen to illustrate the influence of the
      biological variability on the outcome of exposure assessment. Each parameter of
      the exposure assessment (growth parameters, shelf-life conditions) was
      characterized by a probability distribution describing variability and/or
      uncertainty. The impact of the intra-species variability on the result of the
      exposure assessment was then quantified and discussed. Two simple domestic shelf
      life conditions were tested. The results confirm that the biological variability
      has a great impact on the accuracy of the result and should not be systematically
      neglected.

PMID- 10939271
TI  - Sensitivity analysis in quantitative microbial risk assessment.
AB  - The occurrence of foodborne disease remains a widespread problem in both the
      developing and the developed world. A systematic and quantitative evaluation of
      food safety is important to control the risk of foodborne diseases. World-wide,
      many initiatives are being taken to develop quantitative risk analysis. However,
      the quantitative evaluation of food safety in all its aspects is very complex,
      especially since in many cases specific parameter values are not available. Often
      many variables have large statistical variability while the quantitative effect
      of various phenomena is unknown. Therefore, sensitivity analysis can be a useful
      tool to determine the main risk-determining phenomena, as well as the aspects
      that mainly determine the inaccuracy in the risk estimate. This paper presents
      three stages of sensitivity analysis. First, deterministic analysis selects the
      most relevant determinants for risk. Overlooking of exceptional, but relevant
      cases is prevented by a second, worst-case analysis. This analysis finds relevant
      process steps in worst-case situations, and shows the relevance of variations of
      factors for risk. The third, stochastic analysis, studies the effects of
      variations of factors for the variability of risk estimates. Care must be taken
      that the assumptions made as well as the results are clearly communicated.
      Stochastic risk estimates are, like deterministic ones, just as good (or bad) as
      the available data, and the stochastic analysis must not be used to mask lack of
      information. Sensitivity analysis is a valuable tool in quantitative risk
      assessment by determining critical aspects and effects of variations.

PMID- 10939272
TI  - Microbiological risk assessment in Europe: the next decade.
AB  - Under the Agreement on the Application of Sanitary and Phytosanitary Measures
      that came into force in 1995, it was stipulated that all World Trade Organisation
      (WTO) members are required to ensure that their sanitary and phytosanitary
      measures are based on assessment of the risks to human, animal or plant life or
      health. In doing so, they must take into account risk assessment techniques
      developed by relevant international organisations. WHO and FAO are two such
      international organisations that are of very high standard and influence. Their
      executive body, the Codex Alimentarius Commission has developed the concept of
      Microbiological Risk Assessment (MRA) in a wider framework called Risk Analysis.
      The aim of Risk Analysis is to provide a global standard for the interpretation
      of the acceptability of risks associated to foods to which consumers might be
      exposed. Microbiological Risk Assessment is an essential element of Risk Analysis
      because it specifies risks related to pathogenic micro-organisms in the food
      chain on the basis of sound science, combining qualitative and quantitative data
      in the areas of epidemiology and pathogenicity of micro-organisms with food
      production and handling. The concept is still in its infancy but is gaining wide
      acceptance globally. This paper will describe an inventory of MRA developments in
      Europe carried out under auspicion of the European Commission. It also gives the
      results of a literature survey concerning scientific publications on the topic
      MRA in which the activities in Europe are compared to those elsewhere.

PMID- 10939273
TI  - Bibliography of food microbiology.

PMID- 10939274
TI  - New developments in the analysis of gene expression.
AB  - An understanding of the relationship between gene expression, protein expression
      and the influences of genetic responses upon gene function is vital before we can
      understand the complexity of genomes. Traditional methods for the study of gene
      expression are limited to studying small groups of genes at a time and a source
      of pure starting material has been difficult to obtain. Recent technological
      advances have enabled large numbers of genes, from specific cell populations, to
      be studied in a single experiment. Laser capture microdissection (LCM) and
      microarray technology are providing the next revolution in the study of gene
      expression. LCM-based molecular analysis of histopathological lesions can be
      applied to any disease process that is accessible through tissue sampling.
      Examples include: (i) mapping the field of genetic changes associated with
      oxidative stress; (ii) analysis of gene expression patterns in atherosclerotic
      tissues, sites of inflammation and Alzheimer's disease plaques; (iii) infectious
      micro-organism diagnosis; and (iv) typing of cells within disease foci.
      Microarray hybridisation glass chips spotted with sets of genes can then be used
      to obtain a molecular fingerprint of gene expression in the microdissected cells.
      The variation of expressed genes or alterations in the cellular DNA that
      correlate with a particular disease state can be compared within or between
      individual samples. The identification of gene expression patterns may provide
      vital information for the understanding of the disease process and may contribute
      to diagnostic decisions and therapies tailored to the individual patient.
      Molecules found to be associated with defined pathological lesions may provide
      clues about new therapeutic targets in the future.

PMID- 10939275
TI  - Antioxidant levels in the rat brain after nitric oxide synthase inhibition: a
      preliminary report.
AB  - Protective effects of NOS inhibitors and free radical scavengers in cerebral
      ischemia are well documented. The present study was undertaken to determine the
      possible effects of NOS inhibition on brain antioxidants. Levels of both
      enzymatic [glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD)]
      and non-enzymatic [reduced glutathione (GSH)] antioxidants following nitric oxide
      synthase (NOS) inhibition by N(G)-nitro-L-arginine methyl ester (L-NAME), D-NAME
      or 7-nitroindazole (7-NI) have been investigated. NOS activity and antioxidant
      levels in the rat cerebellum and medulla were estimated 1 h after treatment with
      L-NAME (10, 30 and 100 mg/kg, i.p.), D-NAME (100 mg/kg, i.p.) or 7-NI (25 mg/kg,
      i.p.). L-NAME and 7-NI inhibited NOS activity in a dose-dependent manner. D-NAME
      also exhibited significant NOS inhibition. The activity of SOD and the GSH level
      remained unaltered following NOS inhibition. However, L-NAME and D-NAME at 100
      mg/kg attenuated GPx activity in the cerebellum, though 7-NI had no effect. L
      NAME inhibited catalase activity in medulla only at 30 mg/kg, but had no effect
      in cerebellum. However, 7-NI (25 mg/kg), D-NAME and L-NAME at 100 mg/kg did not
      affect catalase activity in the rat brain. Thus, NOS inhibition by the three
      agents did not have major effects on brain antioxidant levels.

PMID- 10939276
TI  - Effects of oxygen on kynurenine-3-monooxygenase activity.
AB  - Kynurenine-3-monooxygenase (KM), the third enzyme in the kynurenine (KYN) pathway
      from tryptophan to quinolinic acid (QA), is a monooxygenase requiring oxygen,
      NADPH and FAD for the catalytic oxidation of L-kynurenine to 3-hydroxykynurenine
      and water. KM is innately low in the brain and similar in activity to indoleamine
      oxidase, the rate-limiting pathway enzyme. Accumulation in the CNS of QA, a known
      excitotoxin, is proposed to cause convulsions in several pathologies. Thus, we
      theorized that hyperbaric oxygen (HBO) induced convulsions arise from increased
      QA via oxygen K, effects on this pathway [Brown OR, Draczynska-Lusiak. Oxygen
      activation and inactivation of quinolinate-producing and iron-requiring 3
      hydroxyanthranilic acid oxidase: a role in hyperbaric oxygen-induced convulsions?
      Redox Report 1995; 1: 383-385]. To complement prior studies on the effects of
      oxygen on pathway enzymes, in this paper we report the effects of oxygen on KM.
      Brain and liver KM enzyme are not known to be identical, and some systemically
      produced KYN pathway intermediates can permeate the brain and might stimulate the
      brain pathway. Thus, KM from both brain and liver was assayed at various oxygen
      substrate concentrations to evaluate, in vitro, the potential effects of
      increases in oxygen, as would occur in mammals breathing therapeutic and
      convulsive HBO. In crude tissue extracts, KM was not activated during incubation
      in HBO up to 6 atm. The effects of oxygen as substrate on brain and liver KM
      activity was nearly identical: activity was nil at zero oxygen with an apparent
      oxygen Km of 20-22 microM. Maximum KM activity occurred at about 1000 microM
      oxygen and decreased slightly to plateau from 2000 to 8000 microM oxygen. This
      compares to approximately 30-40 microM oxygen typically reported for brain tissue
      of humans or rats breathing air, and an unknown but surely much lower value
      (perhaps below 1 microM) intracellularly at the site of KM. Thus HBO, as used
      therapeutically and at convulsive pressures, likely stimulates flux through the
      KM-catalyzed step of the KYN pathway in liver and in brain and could increase
      brain QA, by Km effects on brain KM, or via increased KM pathway intermediates
      produced systemically (in liver) and transported into the brain.

PMID- 10939277
TI  - Transplasma membrane redox activity of monocytes/macrophages.

PMID- 10939278
TI  - Lysosomotropic detergents induce time- and dose-dependent apoptosis/necrosis in
      cultured cells.

PMID- 10939279
TI  - Lymphocyte 5'-ectonucleotidase: an indicator of oxidative stress in humans?
AB  - Lymphocytic 5'-ectonucleotidase (NT) activity previously has been shown to be
      reduced in patients with a high pro-oxidant state. This study shows that NT
      activity is decreased in vitro by exposure to superoxide anions and that
      ascorbate protects against this effect. Also, a putative high pro-oxidant state
      in vivo, as indicated by low tissue ascorbate levels, resulted in a significant
      decrease in NT which an antioxidant intake normalized. These results taken
      together suggest that NT is sensitive to superoxide anion and that it may be a
      good marker of a pro-oxidant state in humans.

PMID- 10939280
TI  - UV-induced changes in the skin: can they be repaired?
AB  - The damaging effects of UVB light have been described previously and include a
      number of changes to multiple cell types. At previous meetings of this society,
      we have shown that Langerhans' cells are the most susceptible to UVB induced
      damage which can be shown as ultrastructural changes in dendrites, nucleus and
      cytoplasm by transmission electron microscopy. We have also shown that their
      patterns of migration from skin to regional lymph node and their ability to
      present antigens to autologous T cells have been profoundly altered by UVB
      irradiation. The aim of this work was to establish if it was possible to reverse
      any of the damage done to Langerhans' cells by UVB exposure by topical
      application of a DNA repair enzyme such as T4N5 endonuclease. These experiments
      were undertaken in a sheep model that allowed collection of cells as they migrate
      from the skin. This allowed for a direct examination of the migration
      characteristics and ultrastructural features of all Langerhans' cells before,
      during, and for 2 weeks after exposure to a single dose of UVB. Results obtained
      from this project indicate that treatment by topical application of DNA repair
      enzyme immediately after UVB irradiation may restore a number of normal immune
      parameters associated with the structure and function of migrating Langerhans'
      cells. It appears that there is a dose related correction of the increased tempo
      of cell migration and some improvements in the number of ultrastructurally
      damaged Langerhans' cells have also been associated with application of higher
      doses of DNA repair enzyme. These preliminary findings indicate that some
      potential therapeutic benefits are associated with the use of such agents in
      reversing the immunological damage caused by exposure to erythemal doses of UVB
      light.

PMID- 10939281
TI  - Screening marine natural products for selective inhibitors of key kynurenine
      pathway enzymes.
AB  - Kynurenine, a metabolite of tryptophan along the 'kynurenine pathway', is at a
      branch point of the pathway which can lead to the synthesis of both quinolinic
      acid (QUIN) and kynurenic acid (KYNA). KYNA is an antagonist of glutamate
      receptors; however, QUIN is a selective agonist of NMDA receptors, and has been
      shown to act as an excitotoxic agent. A high QUIN/KYNA ratio has been implicated
      in a variety of neurological diseases in which excitotoxic neuronal cell death is
      found, e.g. AIDS-related dementia, stroke, etc. Inhibiting the key enzymes of
      this pathway (i.e. kynureninase and kynurenine 3-hydroxylase) would lower the
      QUIN/KYNA ratio, which may potentially have neuroprotective effects. We have
      developed high through-put assays for kynurenine pathway enzymes which allow us
      to screen extracts from marine organisms for selective enzyme inhibitors. Active
      metabolites are purified, isolated and identified by HPLC, high-field NMR and
      mass spectral techniques. Extracts from a sponge of the Aka species were found to
      contain a selective inhibitor of kynureninase. We have recently purified and
      identified the active principal as being serotonin sulfate. Related indoleamines,
      serotonin and 5-hydroxyindoleacetic acids are inactive. This finding may be
      suggestive of a novel interaction between the serotoninergic and excitatory amino
      acid pathways.

PMID- 10939282
TI  - Inhibition of haemolysis by the macrophage synthesized antioxidant, 7,8
      dihydroneopterin.

PMID- 10939283
TI  - IDO induction in IFN-gamma activated astroglia: a role in improving cell
      viability during oxidative stress.
AB  - In the central nervous system (CNS), astrocytes play an integral role in the
      maintenance of neuronal viability and function. Inflammation within the CNS
      increases the concentration of oxidative metabolites and, therefore, the
      potential for NAD depletion through increased poly-(ADP-ribose) polymerase (PARP)
      activity. However, the activity of indoleamine 2,3-dioxygenase (IDO), the rate
      limiting enzyme for de novo NAD synthesis, is also markedly increased in
      astrocytes during inflammation. This study investigated the role of IDO induction
      in the maintenance of intracellular NAD and its relationship to improved cell
      viability under conditions of increased oxidative stress in the human astroglioma
      cell line, HTB-138. Treatment with the pro-inflammatory cytokine IFN-gamma
      increased IDO activity in these cells. Intracellular NAD levels also increased
      significantly after treatment with IFN-gamma in the presence of a PARP inhibitor.
      Pretreatment of astroglial cells with IFN-gamma significantly moderated both the
      drop in intracellular NAD concentration and cell death following exposure to
      hydrogen peroxide. These results suggest that induction of IDO and subsequent de
      novo NAD synthesis may contribute to the maintenance of intracellular NAD levels
      and cell viability under conditions of increased oxidative stress.

PMID- 10939284
TI  - Induction of indoleamine 2,3-dioxygenase in primary human macrophages by HIV-1.
AB  - Increased kynurenine pathway metabolism has been implicated in the aetiology of
      the AIDS dementia complex (ADC). The rate limiting enzyme for this pathway is
      indoleamine 2,3-dioxygenase (IDO). We tested the efficacy of different strains of
      HIV-1 (HIV1-BaL, HIV1-JRFL and HIV1-631) to induce IDO in cultured human monocyte
      derived macrophages (MDM). A significant increase in both IDO protein and
      kynurenine synthesis was observed after 48 h in MDM infected with the brain
      derived HIV-1 isolates, laboratory adapted (LA) HIV1-JRFL, and primary isolate
      HIV1-631. In contrast, almost no kynurenine production or IDO protein was evident
      in MDM infected with the high replicating macrophage tropic LA strain, HIV1-BaL.
      The induction of IDO and kynurenine synthesis by HIV1-JRFL and HIV1-631 declined
      to baseline levels by day-8 post-infection. Together, these results indicate that
      only selected strains of HIV-1 are capable of inducing IDO synthesis and
      subsequent oxidative tryptophan catabolism in MDM.

PMID- 10939285
TI  - Characterisation of kynurenine pathway metabolism in human astrocytes and
      implications in neuropathogenesis.
AB  - The role of astrocytes in the production of the neurotoxin quinolinic acid (QUIN)
      and other products of the kynurenine pathway (KP) is controversial. Using
      cytokine-stimulated human astrocytes, we assayed key enzymes and products of the
      KP. We found that astrocytes lack kynurenine-hydroxylase so that large amounts of
      kynurenine (KYN) and kynurenic acid (KYNA) were produced, while minor amounts of
      QUIN were synthesised that were completely degraded. We then showed that
      kynurenine added to macrophages led to significant production of QUIN. These
      results suggest that astrocytes alone are neuroprotective by minimising QUIN
      production and maximising synthesis of KYNA. However, it is likely that, in the
      presence of macrophages and/or microglia, astrocytes are neurotoxic by producing
      large concentrations of KYN that can be metabolised by neighbouring monocytic
      cells to QUIN.

PMID- 10939286
TI  - Tissue distribution of indoleamine 2,3-dioxygenase in normal and malaria-infected
      tissue.
AB  - An immunohistochemical method was developed, using a polyclonal antibody, to
      detect the enzyme indoleamine 2,3-dioxygenase (IDO) in normal and malaria
      infected tissue. Plasmodium berghei ANKA, a cerebral malaria (CM) model, and P.
      berghei K173, a non-cerebral malaria (NCM) model, were used. It was found that
      vascular endothelial cells were the primary site of IDO expression in both models
      of malaria infection and that this response was systemic, with the vascular
      endothelium of brain, heart, lung, spleen and uterus all staining positive. These
      results suggest that IDO is part of a systemic host response to parasite
      infection. Although high levels of IDO production alone may not cause pathology,
      it is possible that when its production is combined with other features of CM,
      such as breakdown of the blood-brain barrier (BBB), metabolites of the kynurenine
      pathway may be able to influence the otherwise tightly regulated, immunologically
      privileged site of the CNS and cause some of the symptoms and pathology observed.

PMID- 10939287
TI  - Protective effects of probucol in two animal models of atherosclerosis.

PMID- 10939288
TI  - A method to determine the fractal dimension of the cross-sectional jaggedness of
      the infarct scar edge.
AB  - This study describes the use of a shareware software package available from the
      National Institutes of Health for computing the fractal dimension. Specifically,
      when fractal analysis is used in its correct context it provides for a
      quantitative description of the space filling properties of two-dimensional
      objects. A rabbit model of post myocardial infarction is described where the
      cross-sectional infarct edge is reconstructed and its jaggedness determined by
      calculating its fractal dimension via the pixel dilation method. The fractal
      dimensions of the anterior and posterior lateral infarct edges were calculated to
      have a mean of 1.16 and 1.29, respectively. In conclusion, the fractal technique
      can be used to describe the complex jaggedness of the infarct edge. This case
      study also illustrates the fact that the complexity of an infarcted area is not
      uniform across the scar. For example, we found that the space filling properties
      of the anterior and posterior borders of a myocardial infarct can differ by more
      than 2-fold.

PMID- 10939289
TI  - Cross-sectional infarct edge jaggedness does not influence ventricular electrical
      stability in a rabbit model of late myocardial infarct healing.
AB  - Previous studies have suggested that the jaggedness of the healed or healing
      infarct edge influences cardiac electrical stability. However, these findings
      have been based on histological observations rather than quantitative
      measurements. The aim of this study was to assess infarct jaggedness by
      calculating its fractal dimension and to examine how this influences cardiac
      electrical stability during late infarct healing in the rabbit. Using programmed
      electrical stimulation, it was found that the fractal dimension did not differ
      significantly in 19 rabbits that had inducible ventricular tachycardia and 16
      that did not. We conclude from these studies in the mature rabbit that infarct
      edge jaggedness does not influence the ease with which ventricular tachycardia is
      induced during late myocardial infarct healing.

PMID- 10939290
TI  - Phenolic acids protect low density lipoproteins from peroxynitrite-mediated
      modification in vitro.
AB  - The role of reactive nitrogen species, such as peroxynitrite, in atherogenesis
      and the protective effect of dietary phenolic compounds are not yet understood.
      In this study, we sought firstly to determine whether phenolic acids become
      nitrated by peroxynitrite and then whether phenolic acid nitration can prevent
      consumption of gamma-tocopherol and thus enhance the resistance of LDL to
      oxidation by peroxynitrite. Coumaric acid was found to be readily nitrated by
      peroxynitrite and it also demonstrated a protective effect on y-tocopherol. Of
      greater significance was its potent inhibition of lipid peroxidation which was
      equal to that of caffeic acid.

PMID- 10939291
TI  - Nitric oxide regulates alkaline phosphatase activity in rat fracture callus
      explant cultures.
AB  - Nitric oxide (NO) is synthesised by a group of enzymes called nitric oxide
      synthases (NOS) and oxidizes to its stable end-products nitrite (NO2-) and
      nitrate (NO3-) We have previously reported in an in vivo rat model that NO is an
      important regulator for rat bone fracture healing. This study examines the
      effects of NO on alkaline phosphatase (ALP) activity in a rat fracture callus
      explant culture system. Explants of rat femoral fracture callus from days 4, 7,
      14 and 28 post fracture induced NO2 release and ALP activity in a biphasic
      temporal manner, with the highest activity on day 7 and the lowest activity on
      day 14. Inhibition of NOS by co-incubation with an NOS inhibitor, S-(2
      aminoethyl) isothiouronium bromide hydrobromide (AETU), inhibited ALP activity by
      an average of 50% at each time point (P <0.01). Supplementation with NO donor 3
      morpholinosydnonomine hydrochloride (SIN-1) at low doses (25 and 0.025 microM)
      increased ALP activity by 20% (P < 0.01). ALP mRNA and histochemical ALP activity
      were localised to osteoblast-like and chondrocyte-like cells within fracture
      callus. The current study provides evidence that NO plays a regulatory role in
      ALP activity during rat fracture healing.

PMID- 10939292
TI  - UVB-induced experimental carcinogenesis: dysregulation of apoptosis and p53
      signalling pathway.

PMID- 10939293
TI  - An investigation into the genotoxic species generated during reduction of
      chromium(VI) by catechol(amine)s.

PMID- 10939294
TI  - Increased cell surface protease activity in UV-irradiated cells undergoing
      apoptosis.
AB  - UVB-irradiated HeLa cells undergoing apoptosis have increased cell surface
      protease (CSP) activity compared to viable or necrotic cells. In order to
      elucidate whether caspase 3 plays a role in the activation of CSP in cells
      undergoing apoptosis, HeLa cell cultures were pre-treated with the caspase
      inhibitor, DEVD, prior to being exposed to 500 Jm(-2) UVB. DEVD significantly
      inhibited caspase 3 activity in cells undergoing apoptosis, but did not affect
      the activation of CSP in these cells. The findings suggest that the activation of
      CSP in apoptotic cells is unrelated to caspase 3 activity.

PMID- 10939295
TI  - Measurement of o- and m-tyrosine as markers of oxidative damage in motor neuron
      disease.

PMID- 10939296
TI  - Dichloroacetate (DCA) reduces brain lactate but increases brain glutamine in
      experimental cerebral malaria: a 1H-NMR study.
AB  - Recent findings that levels of brain lactate and alanine were elevated in murine
      cerebral malaria led us to investigate the effect of dichloroacetate (DCA; 60
      mg/kg), an activator of pyruvate dehydrogenase, on the levels of brain
      metabolites, and on the survival of mice infected with Plasmodium berghei ANKA
      which normally causes lethal cerebral malaria. DCA significantly reduced brain
      lactate and alanine levels when administered to infected mice, had no effect on
      the TCA cycle-related metabolites glutamate, GABA and aspartate and was
      associated with increased brain glutamine levels: 40% of mice thus treated
      survived the normally lethal infection.

PMID- 10939297
TI  - Body contouring using an oral herbal antioxidant formulation--Centelaplus: a dose
      controlled observational study.

PMID- 10939298
TI  - Free radicals in chronic fatigue syndrome: cause or effect?
AB  - We have demonstrated that certain morphological and biochemical changes occur in
      chronic fatigue syndrome (CFS) and in rheumatoid arthritis (RA). These changes in
      RA can be explained by the well-established inappropriate increase in free
      radical generation. The similar changes in CFS suggest a similar explanation and
      a possible role for free radicals in the aetiology of this condition.

PMID- 10939299
TI  - Plasma membrane redox system protects cells against oxidative stress.

PMID- 10939300
TI  - Quantitative analysis of trace gases of breath during exercise using the new SIFT
      MS technique.
AB  - We show how the concentration of the breath gases ammonia, acetone, and isoprene
      vary with time during exercise using the new selected ion flow tube mass
      spectrometry (SIFT-MS) technique. The expired breath concentrations of ammonia,
      acetone and isoprene were observed within the range of 50-500, 100-1400 and 5-400
      ppb, respectively. Increasing acetone levels were observed for most subjects
      during the exercise period. However, isoprene levels decreased with time during
      exercise. Older subjects showed higher levels of isoprene compared with younger
      subjects. The ammonia time profile with exercise showed both decreasing and
      increasing patterns for different subjects.

PMID- 10939301
TI  - UVA and UVB wavebands modulate expression of fasL in mouse skin epidermis.
AB  - In our previous report, we observed different cytokine modulation in mouse
      epidermis by the UVA and UVB wavebands. In the present investigations, the
      effects of irradiation with UVA and UVB on the Fas(CD95)/FasL system have been
      studied because apoptosis mediated by the interaction between Fas and FasL has
      been suggested recently to be associated with UVB-induced immunosuppression in
      mouse skin. Our results show that UVA irradiation following UVB irradiation has
      the ability to reduce the up-regulation of FasL expression in mouse skin
      resulting from the UVB irradiation.

PMID- 10939302
TI  - Protective effect of isoflavone derivative against photocarcinogenesis in a mouse
      model.
AB  - Plant-derived isoflavones are currently receiving much attention because of their
      phyto-estrogenic and antioxidant activities. In this study, we describe novel
      photoprotective effects of one isoflavone derivative from red clover (NV07),
      following its application topically in Skh:HR-1 hairless mice. We found that in
      mice irradiated in the short-term (3 days) with minimally erythemal solar
      simulated UV radiation, topical lotions containing NV07 dose-responsively reduced
      the erythema-associated oedema, the induction of ornithine decarboxylase, and the
      suppression of contact hypersensitivity. In mice irradiated chronically (50
      days), daily application of topical NV07-lotion reduced photocarcinogenesis
      significantly, and appeared to be actively protective during both the initiation
      phase and the later promotion phase of tumour induction.

PMID- 10939303
TI  - Singlet oxygen-mediated protein oxidation: evidence for the formation of reactive
      peroxides.

PMID- 10939304
TI  - Presence of regio-isomeric cholesteryl linoleate hydroperoxides and hydroxides in
      plasma from healthy humans as evidence of free radical-mediated lipid
      peroxidation in vivo.

PMID- 10939305
TI  - Potential role of cannabinoids in Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder caused by a progressive
      loss of dopaminergic neurons of the substantia nigra, resulting from an oxidative
      stress. The lack of dopaminergic neurons is reflected by a disturbed balance of
      the neural circuitry in the basal ganglia. Cannabinoids might alleviate some
      parkinsonian symptoms by their remarkable receptor-mediated modulatory action in
      the basal ganglia output nuclei. Moreover, it was recently observed that some
      cannabinoids are potent antioxidants that can protect neurons from death even
      without cannabinoid receptor activation. It seems that cannabinoids could delay
      or even stop progressive degeneration of brain dopaminergic systems, a process
      for which there is presently no prevention. In combination with currently used
      drugs, cannabinoids might represent, qualitatively, a new approach to the
      treatment of PD, making it more effective.

PMID- 10939306
TI  - Onychomycosis in the elderly.
AB  - Onychomycosis is found more frequently in the elderly, and in more males than
      females. Onychomycosis of the toes is usually caused by dermatophytes, most
      commonly Trichophyton rubrum and T. mentagrophytes. The most common clinical
      presentations are distal and lateral subungual onychomycosis (which usually
      affects the great/first toe) and white superficial onychomycosis (which generally
      involves the third/fourth toes). Only about 50% of all abnormal-appearing nails
      are due to onychomycosis. In the remainder, trauma to the nail, psoriasis and
      conditions such as lichen planus should be considered in the differential
      diagnosis. Therefore, the clinical impression of onychomycosis should be
      confirmed by mycological examination, whenever possible. The management of
      onychomycosis may include no therapy, palliative treatment with mechanical or
      chemical debridement, topical antifungal therapy, oral antifungal agents or a
      combination of treatment modalities. In the US, the only new oral agents approved
      for treatment of onychomycosis are terbinafine and itraconazole. Fluconazole is
      approved for onychomycosis in some other countries. Ciclopirox nail lacquer has
      recently been approved in the US for the treatment of onychomycosis. In some
      other countries topical agents such as amorolfine are also used. Griseofulvin and
      ketoconazole are no longer preferred for the treatment of onychomycosis. The new
      oral antifungal agents are effective and well tolerated in the elderly. Patient
      selection should be based on the history (including systems review and medication
      record), examination and baseline monitoring, if indicated. Laboratory monitoring
      during therapy for onychomycosis varies among physicians. A combination of
      removal of the diseased nail plate or local measures and oral antifungal therapy
      may be optimal in certain instances, e.g. when lateral onychomycosis or
      dermatophytoma are present. For dermatophyte toe onychomycosis the recommended
      duration of therapy with terbinafine is 250 mg/day for 12 weeks. For itraconazole
      (pulse) the regimen is 200 mg twice daily for 1 week on, 3 weeks off, repeated
      for 3 consecutive pulses and with fluconazole the regimen is 150 to 300 mg once
      weekly given for a usual range of 6 to 12 months or until the nail plate has
      grown out. In some instances, if extra therapy is required, one suggestion is
      that 4 weeks of terbinafine or an extra pulse of itraconazole are given between
      months 6 and 9 from the start of therapy. Once cure has been achieved, it is
      important to counsel patients on the strategies of reducing recurrence of
      disease.

PMID- 10939308
TI  - Assessing medication appropriateness in the elderly: a review of available
      measures.
AB  - The disproportionate use of medications, combined with age-related
      pharmacokinetic and pharmacodynamic changes, places older adults at high risk for
      medication related problems (MRPs). MRPs demonstrate significant morbidity,
      mortality and economic impact among healthcare systems. The negative outcomes
      associated with MRPs emphasise the need for more careful and thorough assessments
      of drug therapy among older adults. In the 1990s a number of methods and
      instruments were developed to assist in the assessment of medication
      appropriateness. These tools may be categorised by criteria as: implicit,
      explicit or one utilising a combination of implicit and explicit criteria. This
      article reviews these available tools and outlines the advantages and
      disadvantages of each. In conclusion, those instruments considered to be
      comprised of both implicit and explicit criteria offer a more thorough assessment
      of medication appropriateness.

PMID- 10939310
TI  - Who's on first?

PMID- 10939307
TI  - Use of oral anticoagulants in older patients.
AB  - Recently published American and British guidelines have comprehensively reviewed
      the indications for long term anticoagulation. The best evidence currently
      available supports the use of long term oral anticoagulants in patients with
      nonvalvular atrial fibrillation (NVAF), venous thromboembolic disease, ischaemic
      heart disease, mural thrombi, and mechanical heart valves. Selected patients with
      valvular heart disease, cerebral vascular disease, and peripheral arterial
      disease may also benefit from the use of these drugs. When no specific
      contraindications are present, elderly patients with either paroxysmal or
      persistent NVAF should be considered candidates for treatment with
      anticoagulants. Pooled analyses of the results from 9 randomised trials
      demonstrate that warfarin significantly reduces the risk of ischaemic stroke in
      patients with NVAF, particularly those in a 'high risk' category defined by the
      presence of additional clinical or echocardiographic risk factors. Long term
      anticoagulation does not appear to be justified in patients with NVAF considered
      to be at 'low risk' for stroke. Because the prevalence of NVAF and most other
      cardiovascular conditions increases with advancing age, many elderly patients
      will be candidates for thromboprophylaxis. The potential benefit of long term
      anticoagulation must be carefully weighed against the risk of serious haemorrhage
      in such patients. Bleeding complications with anticoagulant drugs appear to occur
      more frequently in older patients than in younger individuals. Advanced age (>75
      years), intensity of anticoagulation [International Normalised Ratio (INR) >4.0],
      history of cerebral vascular disease (recent or remote), and concomitant use of
      drugs that interfere with haemostasis [aspirin (acetylsalicylic acid) or
      nonsteroidal anti-inflammatory drugs] are among the most important variables in
      determining an individual's risk for major bleeding with anticoagulants. Older
      patients often display increased sensitivity to the effects of warfarin, both in
      the early induction phase and during the long term maintenance phase of therapy.
      Conditions such as congestive heart failure, malignancy, malnutrition, diarrhoea
      and unsuspected vitamin K deficiency, enhance the prothrombin time response. The
      decision to interrupt anticoagulant therapy before elective surgery in elderly
      patients should evaluate the thrombotic risk of such a manoeuvre versus the risk
      of bleeding if anticoagulants are continued. In non-surgical patients,
      excessively elevated INRs without associated haemorrhage can usually be managed
      by simply witholding one or several doses of warfarin. If more rapid reversal is
      needed, small doses of phytomenadione (vitamin K1) can be administered safely
      without overcorrection or the development of vitamin K-induced warfarin
      resistance.

PMID- 10939311
TI  - Spasm of the near reflex mimicking deteriorating accommodative esotropia.
AB  - PURPOSE: To describe a patient with accommodative esotropia who developed spasm
      of the near reflex. CASE REPORT: A 6-year-old girl with a history of successfully
      treated refractive, accommodative esotropia suddenly developed spasm of the near
      reflex after the death of a relative. The condition resolved after 2 months.
      CONCLUSION: Spasm of the near reflex should be considered in children with
      accommodative esotropia who seem to deteriorate and become esotropic once again
      while wearing their hyperopic glasses.

PMID- 10939309
TI  - Risperidone: a review of its use in the management of the behavioural and
      psychological symptoms of dementia.
AB  - Risperidone is a benzisoxazole derivative which has proven efficacy against the
      positive and negative symptoms of schizophrenia. It has more recently been
      investigated and shown efficacy as a treatment for the behavioural and
      psychological symptoms associated with dementia in the elderly. Risperidone has
      pharmacological properties resembling those of the atypical antipsychotic
      clozapine and an improved tolerability profile compared with the conventional
      antipsychotic haloperidol. Risperidone has antagonistic activity primarily at
      serotonin 5-HT2A and dopamine D2 receptors. In the first 2 large, well controlled
      trials of an antipsychotic agent used in the treatment of elderly patients with
      Alzheimer's dementia, vascular dementia or mixed dementia, risperidone 1 mg/day
      was at least as effective as haloperidol and superior to placebo, as assessed by
      the rating scales for global behaviour, aggression and psychosis. In extension
      phases of the 2 trials, clinical benefits were maintained for treatment periods
      of up to 1 year, with an incidence rate of tardive dyskinesia (2.6%) one-tenth of
      that seen with conventional antipsychotics. Risperidone, administered at a low
      dosage of 1 mg/day was associated with fewer extrapyramidal symptoms compared
      with haloperidol in elderly patients. Risperidone was well tolerated with no
      clinically relevant abnormalities in laboratory tests, vital signs or
      electrocardiogram results. CONCLUSION: The efficacy of risperidone has been
      demonstrated in the treatment of the behavioural and psychological symptoms
      associated with dementia in the elderly. Preliminary results from 1-year
      extension studies confirm the favourable efficacy and tolerability profile of
      risperidone 1 mg/day. Although head to head studies with other atypical
      antipsychotic agents are required and the long term use of the drug requires
      clarification, risperidone represents a generally well tolerated and effective
      treatment in the management of dementia-associated behavioural and psychological
      symptoms in the elderly.

PMID- 10939312
TI  - Optical coherence tomography: an introduction to the technique and its use.
AB  - This report describes the new optical imaging technique of optical coherence
      tomography (OCT). OCT is capable of high-resolution, micrometer-scale, cross
      sectional imaging of biological tissue. The OCT for ophthalmic application uses
      843-nm, near-infrared light, which produces a longitudinal resolution of 10 to 20
      microm and a penetration depth of a few millimeters. The scans are displayed in a
      false color representation scale on which warm colors represent areas of high
      optical reflectivity and cool colors represent areas of minimal or no
      reflectivity. A cross-sectional view similar to a histology section is obtained.
      The cornea, iris, and lens may be visualized as well as the retina and optic
      nerve. OCT has been used to investigate several ocular diseases. These include
      macular disease, genetic retinal disease, retinal detachment and retinoschisis,
      choroidal tumors, optic nerve disorders, and glaucoma.

PMID- 10939313
TI  - Prevalence of dry eye subtypes in clinical optometry practice.
AB  - BACKGROUND: Dry eye conditions are now recognized as having multiple causes. A
      subtype-based dry eye diagnostic protocol was developed to determine the
      prevalence of dry eye and dry eye subtypes, and the effects of age and gender, in
      subjects presenting to clinical optometry practice. METHODS: Dry eye diagnostic
      criteria were: presence of one or more McMonnies dry eye survey primary symptoms,
      fluorescein tear break time < 10 s and rose bengal ocular surface staining. Dry
      eye subtype differential diagnosis was made predominantly on the basis of
      biomicroscopic signs. Subtype categories were: lipid anomaly dry eye (LADE),
      aqueous tear deficiency (ATD), primary mucin anomalies, allergic/toxic dry eye
      (ADE), primary epitheliopathies and lid surfacing/blinking anomalies (LSADE).
      RESULTS: Dry eye prevalence was 10.8% for n = 1584 subjects. Dry eye was
      significantly more prevalent in subjects 40 years or older (18.1%) compared with
      those < 40 years (7.3%) (p = 0.001). LADE was the most prevalent subtype (4.0%),
      followed by ADE at 3.1%, LSADE at 1.8%, and ATD at 1.7%. ATD was the only subtype
      with a significant gender prevalence difference, being more prevalent in women (p
      = 0.0023). The prevalence of LADE and ATD were significantly greater in those 40
      years or older (p = 0.001 and p = 0.0023 respectively). CONCLUSIONS: The results
      of this study support a subtype-based approach to dry eye diagnosis and
      management in clinical practice.

PMID- 10939314
TI  - The limitations imposed on reading by low vision aids.
AB  - INTRODUCTION: The changes that occur in the reading eye movements of normally
      sighted readers were measured as they used hand magnifiers to identify how these
      devices contribute to the slow reading of visually-impaired patients. METHODS:
      Subjects inexperienced in magnifier use read texts containing two sizes of print,
      using hand magnifiers of two different powers, held at two different eye-to
      magnifier distances. The effect of magnification (up to 13.5x) and field-of-view
      (FOV) (2-45 characters) could be assessed independently. RESULTS: Reading speed
      decreased with increasing magnification because the size of the saccades did not
      increase in proportion to the magnification: for a given level of magnification,
      decreasing the FOV and decreasing the viewing distance both reduce the size of
      the saccades even further. The overall reading speed is only slowed significantly
      when the FOV restriction is extreme (two characters' width). CONCLUSIONS: Two
      mechanisms seem to be used spontaneously by normally sighted readers to mitigate
      the limitation of reading speed created by the shortened saccades: head movement
      in the direction of reading and retinal image slip during fixation.

PMID- 10939315
TI  - Prentice's equation and generalizations.
AB  - The purpose of this note is to clarify confusion over the range of applicability
      of Prentice's equation for the calculation of prismatic effects in lenses. Making
      use of the concept of the ray transference in Gaussian and linear optics, the
      paper obtains generalized forms of Prentice's equation that apply in various
      situations. Redefinition of prismatic deviation as change in reduced direction of
      a ray makes Prentice's equation valid for thin systems in media of any index of
      refraction. In particular, the equation then holds for a single refracting
      surface. It does not hold in general for thick systems, although there are some
      special cases in which it does apply. The appropriate equation is presented for
      thick systems in general. The correct form of power to use in the equations is
      equivalent power and not back-vertex power. A generalized form of Prentice's
      equation applies to astigmatic systems, including single refracting surfaces and
      thin lenses. An analog of Prentice's equation gives the transverse displacement
      of a ray across a system as a function of the incident-reduced direction of the
      ray.

PMID- 10939316
TI  - Group interventions for anger in people with intellectual disabilities.
AB  - This paper describes an evaluation of a group intervention for reducing
      inappropriately expressed anger (as aggression) in people with intellectual
      disabilities. Group intervention was compared to a treatment as usual group
      consisting of people referred to the group but who had to wait to participate.
      The intervention used was based on the work of Novaco (1976; 1978) and Benson
      (1994). However, further modifications to the group that emphasized the
      contextual perspective of anger, such as the participants being accompanied by a
      support worker and more collaborative recording procedures, were devised. A
      reduction in expressed anger and measured levels of depression occurred after
      group treatment. Reductions in expressed anger were maintained at 6 and 12 months
      follow up. However, scores on the depression scale tended to increase on follow
      up. While caution must be expressed when considering these results, this type of
      intervention shows promise for reducing inappropriately expressed anger in people
      with intellectual disabilities Suggestions are made for future research and
      clinical practice.

PMID- 10939317
TI  - Skill acquisition in parents of children with developmental disabilities:
      interaction between skill type and instructional format.
AB  - A variety of instructional formats have been used to teach parents of children
      with developmental disabilities how to implement treatments for problem behavior.
      Although several authors have suggested that the efficacy of various
      instructional methods might depend on the type of skill taught to parents, no
      studies have been designed to systematically explore this potential interaction.
      In this preliminary study, three parents who requested outpatient services for
      treatment of their children's problem behavior were taught to implement multiple
      treatment components. Therapists employed the most cost-efficient method first
      (i.e., written and verbal instructions) to teach prescribed behavior management
      strategies (e.g., differential reinforcement). If the parent's behavior failed to
      meet a performance criterion, feedback was included in training sessions. The
      efficacy of verbal and written instructions varied across different components of
      the child's treatment program.

PMID- 10939318
TI  - Emergent symbolic relations in speakers and nonspeakers.
AB  - Eight adults with developmental disabilities and four typically developing
      preschool children participated in an experiment studying emergent stimulus
      stimulus relations after match-to-sample instruction. Participants were taught to
      match lexigrams (arbitrary graphic stimuli) to objects. Each object was
      functionally related to another object in the teaching set. For example, brush
      and comb were members of the teaching set. Most participants were able to select
      objects when the objects were named in pretests. Postteaching probes assessed
      emergent relations between spoken names and lexigrams. In addition, we included
      probes to detect emergent relations between related lexigrams. That is, would
      participants select the lexigram for comb when the experimenter displayed the
      lexigram for brush (without explicit teaching)? Two preschool children and five
      adults with developmental disabilities showed emergent relations between
      lexigrams and spoken words. However, only two preschool children showed the
      emergent lexigram to related lexigram relations.

PMID- 10939319
TI  - Noncontingent attention for the treatment of excessive medical complaints in a
      medically fragile man with mental retardation.
AB  - Providing medical care to individuals with developmental disabilities who have
      medical problems may pose several challenges with regard to accurate and reliable
      report of symptoms. In addition, medical complaints may take on operant functions
      such as an attention function or an escape function as a result of the natural
      consequences in the environment. It may be difficult to withhold reinforcers for
      medical complaints such as attention or escape, making a standard analog
      functional analysis or extinction-based intervention less appropriate. Recent
      studies have shown that noncontingent reinforcement without extinction and
      noncontingent reinforcement using alternative reinforcers can be effective in
      reducing problem behavior. One practical implication of these findings is that
      noncontingent reinforcement may be an appropriate treatment in cases where the
      reinforcer responsible for behavioral maintenance cannot be identified or
      withheld. In the current study, attention served as a reinforcer for a young man
      with medical complaints and noncontingent attention without ignoring effectively
      reduced the participant's excessive medical complaints.

PMID- 10939320
TI  - Questions about behavioral function (QABF): a behavioral checklist for functional
      assessment of aberrant behavior.
AB  - Functional assessment is a method to identify the relationships between a
      behavior of interest and an individual's environment. Traditional methods for
      functional assessment have relied on experimental techniques in which analog
      sessions are designed to replicate conditions in the individual's environment.
      However, these techniques can be time-consuming, require advanced training, and
      rely on the availability of extensive resources in the individual's setting.
      Development of a brief functional assessment checklist would circumvent these
      difficulties and meet clinical needs for efficient assessment methods. The
      current study provides psychometric data for the Questions About Behavioral
      Function. These data include test-retest, inter-rater, and internal consistency.

PMID- 10939322
TI  - Birth of a synapse: not such long labor.

PMID- 10939321
TI  - Timing is everything.

PMID- 10939323
TI  - Regulating receptor levels at a developing synapse.

PMID- 10939324
TI  - Persistent activation of cAMP-dependent protein kinase and the induction of long
      term memory.

PMID- 10939325
TI  - Teaching the brain to see.

PMID- 10939326
TI  - Filopodia, spines, and the generation of synaptic diversity.

PMID- 10939327
TI  - Gain modulation: a major computational principle of the central nervous system.

PMID- 10939328
TI  - Monitoring presynaptic calcium dynamics in projection fibers by in vivo loading
      of a novel calcium indicator.
AB  - Fluorometric calcium measurements have revealed presynaptic residual calcium
      (Ca(res)) to be an important regulator of synaptic strength. However, in the
      mammalian brain, it has not been possible to monitor Ca(res) in fibers that
      project from one brain region to another. Here, we label neuronal projections by
      injecting dextran-conjugated calcium indicators into brain nuclei in vivo.
      Currently available dextran conjugates distort Ca(res) due to their high affinity
      for calcium. Therefore, we synthesized a low-affinity indicator, fluo-4 dextran,
      that can more accurately measure the amplitude and time course of Ca(res). We
      then demonstrate the utility of fluo-4 dextran by measuring Ca(res) at climbing
      fiber presynaptic terminals. This method promises to facilitate the study of many
      synapses in the mammalian CNS, both in brain slices and in vivo.

PMID- 10939329
TI  - Reelin binds alpha3beta1 integrin and inhibits neuronal migration.
AB  - Mice that are mutant for Reelin or Dab1, or doubly mutant for the VLDL receptor
      (VLDLR) and ApoE receptor 2 (ApoER2), show disorders of cerebral cortical
      lamination. How Reelin and its receptors regulate laminar organization of
      cerebral cortex is unknown. We show that Reelin inhibits migration of cortical
      neurons and enables detachment of neurons from radial glia. Recombinant and
      native Reelin associate with alpha3beta1 integrin, which regulates neuron-glia
      interactions and is required to achieve proper laminar organization. The effect
      of Reelin on cortical neuronal migration in vitro and in vivo depends on
      interactions between Reelin and alpha3beta1 integrin. Absence of alpha3beta1
      leads to a reduction of Dab1, a signaling protein acting downstream of Reelin.
      Thus, Reelin may arrest neuronal migration and promote normal cortical lamination
      by binding alpha3beta1 integrin and modulating integrin-mediated cellular
      adhesion.

PMID- 10939330
TI  - Timing-based LTP and LTD at vertical inputs to layer II/III pyramidal cells in
      rat barrel cortex.
AB  - Experience-dependent plasticity in somatosensory (S1) and visual (V1) cortex
      involves rapid depression of responses to a deprived sensory input (a closed eye
      or a trimmed whisker). Such depression occurs first in layer II/III and may
      reflect plasticity at vertical inputs from layer IV to layer II/III pyramids.
      Here, I describe a timing-based, associative form of long-term potentiation and
      depression (LTP/LTD) at this synapse in S1. LTP occurred when excitatory
      postsynaptic potentials (EPSPs) led single postsynaptic action potentials (APs)
      within a narrow temporal window, and LTD occurred when APs led EPSPs within a
      significantly broader window. This long LTD window is unusual among timing-based
      learning rules and causes EPSPs that are uncorrelated with postsynaptic APs to
      become depressed. This behavior suggests a simple model for depression of
      deprived sensory responses in S1 and V1.

PMID- 10939331
TI  - Assembly of new individual excitatory synapses: time course and temporal order of
      synaptic molecule recruitment.
AB  - Time-lapse microscopy, retrospective immunohistochemistry, and cultured
      hippocampal neurons were used to determine the time frame of individual
      glutamatergic synapse assembly and the temporal order in which specific molecules
      accumulate at new synaptic junctions. New presynaptic boutons capable of activity
      evoked vesicle recycling were observed to form within 30 min of initial
      axodendritic contact. Clusters of the presynaptic active zone protein Bassoon
      were present in all new boutons. Conversely, clusters of the postsynaptic
      molecule SAP90/PSD-95 and glutamate receptors were found on average only
      approximately 45 min after such boutons were first detected. AMPA- and NMDA-type
      glutamate receptors displayed similar clustering kinetics. These findings suggest
      that glutamatergic synapse assembly can occur within 1-2 hr after initial contact
      and that presynaptic differentiation may precede postsynaptic differentiation.

PMID- 10939332
TI  - Presynaptic glutamic acid decarboxylase is required for induction of the
      postsynaptic receptor field at a glutamatergic synapse.
AB  - We have systematically screened EMS-mutagenized Drosophila for embryonic lethal
      strains with defects in glutamatergic synaptic transmission. Surprisingly, this
      screen led to the identification of several alleles with missense mutations in
      highly conserved regions of Dgad1. Analysis of these gad mutants reveals that
      they are paralyzed owing to defects in glutamatergic transmission at the
      neuromuscular junction. Further electrophysiological and immunohistochemical
      examination reveals that these mutants have greatly reduced numbers of
      postsynaptic glutamate receptors in an otherwise morphologically normal synapse.
      By overexpressing wild-type Dgad1 in selected neurons, we show that GAD is
      specifically required in the presynaptic neuron to induce a postsynaptic
      glutamate receptor field, and that the level of postsynaptic receptors is closely
      dependent on presynaptic GAD function. These data demonstrate that GAD plays an
      unexpected role in glutamatergic synaptogenesis.

PMID- 10939333
TI  - The cone pedicle, a complex synapse in the retina.
AB  - Cone pedicles, the synaptic terminals of cone photoreceptors, are connected in
      the macaque monkey retina to several hundred postsynaptic dendrites. Using light
      and electron microscopy, we found underneath each cone pedicle a laminated
      distribution of dendritic processes of bipolar and horizontal cells. Superimposed
      were three strata of glutamate receptor (GluR) aggregates, including a novel
      layer of glutamate receptors clustered at desmosome-like junctions. They are,
      most likely, postsynaptic densities on horizontal cell dendrites. GABA(A) and
      GABA(C) receptors are aggregated on bipolar cell dendrites in a narrow band
      underneath the cone pedicle. Glutamate released from cone pedicles and GABA
      released from horizontal cell dendrites act not only through direct synaptic
      contacts but also (more so) through diffusion to the appropriate receptors.

PMID- 10939334
TI  - A trafficking checkpoint controls GABA(B) receptor heterodimerization.
AB  - Surface expression of GABA(B) receptors requires heterodimerization of GB1 and
      GB2 subunits, but little is known about mechanisms that ensure efficient
      heterodimer assembly. We found that expression of the GB1 subunit on the cell
      surface is prevented through a C-terminal retention motif RXR(R); this sequence
      is reminiscent of the ER retention/retrieval motif RKR identified in subunits of
      the ATP-sensitive K+ channel. Interaction of GB1 and GB2 through their C-terminal
      coiled-coil alpha helices masks the retention signal in GB1, allowing the plasma
      membrane expression of the assembled complexes. Because individual GABA(B)
      receptor subunits and improperly assembled receptor complexes are not functional
      even if expressed on the cell surface, we conclude that a trafficking checkpoint
      ensures efficient assembly of functional GABA(B) receptors.

PMID- 10939335
TI  - Targeting of PKA to glutamate receptors through a MAGUK-AKAP complex.
AB  - Compartmentalization of glutamate receptors with the signaling enzymes that
      regulate their activity supports synaptic transmission. Two classes of binding
      proteins organize these complexes: the MAGUK proteins that cluster glutamate
      receptors and AKAPs that anchor kinases and phosphatases. In this report, we
      demonstrate that glutamate receptors and PKA are recruited into a macromolecular
      signaling complex through direct interaction between the MAGUK proteins, PSD-95
      and SAP97, and AKAP79/150. The SH3 and GK regions of the MAGUKs mediate binding
      to the AKAP. Cell-based studies indicate that phosphorylation of AMPA receptors
      is enhanced by a SAP97-AKAP79 complex that directs PKA to GluR1 via a PDZ domain
      interaction. As AMPA receptor phosphorylation is implicated in regulating
      synaptic plasticity, these data suggest that a MAGUK-AKAP complex may be
      centrally involved.

PMID- 10939336
TI  - Potentiation of neuronal L calcium channels by IGF-1 requires phosphorylation of
      the alpha1 subunit on a specific tyrosine residue.
AB  - Insulin-like growth factor 1 (IGF-1) rapidly potentiates N and L calcium channel
      currents in cerebellar granule neurons by an unknown mechanism. Here, we show
      that the L channel alpha1C subunit is tyrosine phosphorylated in response to IGF
      1. Moreover, expression of kinase-dead c-Src in neurons or acute block of Src
      family kinases with a cell-permeable inhibitor specifically blocks L channel
      potentiation. Purified Src kinase phosphorylates tyrosine residue Y2122 of the C
      terminus of neuronal alpha1C in vitro, and c- and v-Src directly bind the C
      terminus. When expressed in neuroblastoma cells, point mutation of Y2122 prevents
      both tyrosine phosphorylation of alpha1C and IGF-1 potentiation. Our data provide
      a biochemical mechanism whereby phosphorylation of a single specific tyrosine
      residue rapidly modifies ion channel physiology.

PMID- 10939337
TI  - Tetanic stimulation recruits vesicles from reserve pool via a cAMP-mediated
      process in Drosophila synapses.
AB  - At Drosophila neuromuscular junctions, there are two synaptic vesicle pools,
      namely the exo/endo cycling pool (ECP) and the reserve pool (RP). We studied the
      recruitment process from RP using a fluorescent dye, FMI-43. During high
      frequency nerve stimulation, vesicles in RP were recruited for release, and
      endocytosed vesicles were incorporated into both pools, whereas with low
      frequency stimulation, vesicles were incorporated into and released from ECP.
      Release of vesicles from RP was detected electrophysiologically after emptying
      vesicles in the ECP of transmitter by a H+ pump inhibitor. Recruitment from RP
      was depressed by inhibitors of steps in the cAMP/PKA cascade and enhanced by
      their activators. In rutabaga (rut) with low cAMP levels, mobilization of
      vesicles from RP during tetanic stimulation was depressed, while it was enhanced
      in dunce (dnc) with high cAMP levels.

PMID- 10939338
TI  - nalyot, a mutation of the Drosophila myb-related Adf1 transcription factor,
      disrupts synapse formation and olfactory memory.
AB  - nalyot (nal) is a novel olfactory memory mutant of Drosophila, encoding Adf1, a
      myb-related transcription factor. Following extended training sessions, Adf1
      mutants show normal early memory but defective longterm memory. Adf1 shows
      widespread spatiotemporal expression, yet mutant alleles reveal no discernible
      disruptions in gross morphology of the nervous system. Studies at the larval
      neuromuscular junction, however, reveal a role for Adf1 in the modulation of
      synaptic growth-in contrast to the role established for dCREB2 in the control of
      synaptic function (Davis et al., 1996). These findings suggest that Adf1 and
      dCREB2 regulate distinct transcriptional cascades involved in terminal stages of
      synapse maturation. More generally, Adf1 provides a novel link between molecular
      mechanisms of developmental and behavioral plasticity.

PMID- 10939339
TI  - Prolonged activation of cAMP-dependent protein kinase during conditioning induces
      long-term memory in honeybees.
AB  - To investigate the function cAMP-dependent protein kinase (PKA) exerts in the
      induction of long-term memory, changes in PKA activity induced by associative
      learning in vivo were measured in the antennal lobes (ALs) of honeybees. The
      temporal dynamics of PKA activation depend on both the sequence of conditioned
      and unconditioned stimuli and the number of conditioning trials. Only multiple
      trial conditioning, which induces long-term memory (LTM), leads to a profound
      prolongation of PKA activation mediated by the NO/cGMP system. Imitation of this
      prolonged PKA activation in the ALs in combination with single-trial conditioning
      is sufficient to induce LTM. These findings not only demonstrate the close
      connection between conditioning procedure and temporal dynamics in PKA activation
      but also reveal that already during conditioning a distinct temporal pattern of
      PKA activation is critical for LTM induction in intact animals.

PMID- 10939340
TI  - Trajectory encoding in the hippocampus and entorhinal cortex.
AB  - We recorded from single neurons in the hippocampus and entorhinal cortex (EC) of
      rats to investigate the role of these structures in navigation and memory
      representation. Our results revealed two novel phenomena: first, many cells in
      CA1 and the EC fired at significantly different rates when the animal was in the
      same position depending on where the animal had come from or where it was going.
      Second, cells in deep layers of the EC, the targets of hippocampal outputs,
      appeared to represent the similarities between locations on spatially distinct
      trajectories through the environment. Our findings suggest that the hippocampus
      represents the animal's position in the context of a trajectory through space and
      that the EC represents regularities across different trajectories that could
      allow for generalization across experiences.

PMID- 10939342
TI  - A semi-parametric hybrid neural model for nonlinear blind signal separation.
AB  - Nonlinear blind signal separation is an important but rather difficult problem.
      Any general nonlinear independent component analysis algorithm for such a problem
      should specify which solution it tries to find. Several recent neural networks
      for separating the post nonlinear blind mixtures are limited to the diagonal
      nonlinearity, where there is no cross-channel nonlinearity. In this paper, a new
      semi-parametric hybrid neural network is proposed to separate the post
      nonlinearly mixed blind signals where cross-channel disturbance is included. This
      hybrid network consists of two cascading modules, which are a neural nonlinear
      module for approximating the post nonlinearity and a linear module for separating
      the predicted linear blind mixtures. The nonlinear module is a semi-parametric
      expansion made up of two sub-networks, one of which is a linear model and the
      other of which is a three-layer perceptron. These two sub-networks together
      produce a "weak" nonlinear operator and can approach relatively strong
      nonlinearity by tuning parameters. A batch learning algorithm based on the
      entropy maximization and the gradient descent method is deduced. This model is
      successfully applied to a blind signal separation problem with two sources. Our
      simulation results indicate that this hybrid model can effectively approach the
      cross-channel post nonlinearity and achieve a good visual quality as well as a
      high signal-to-noise ratio in some cases.

PMID- 10939341
TI  - Effects of visual experience on the representation of objects in the prefrontal
      cortex.
AB  - The perception and recognition of objects are improved by experience. Here, we
      show that monkeys' ability to recognize degraded objects was improved by several
      days of practice with these objects. This improvement was reflected in the
      activity of neurons in the prefrontal (PF) cortex, a brain region critical for a
      wide range of visual behaviors. Familiar objects activated fewer neurons than did
      novel objects, but these neurons were more narrowly tuned, and the object
      representation was more resistant to the effects of degradation, after
      experience. These results demonstrate a neural correlate of visual learning in
      the PF cortex of adult monkeys.

PMID- 10939344
TI  - Variable sensitivity in unsupervised clustering tasks with an n-tuple-based self
      organising neural network.
AB  - This article investigates the application of the SOLNN (Self-Organising Logic
      Neural Network) n-tuple-based network to character recognition and image
      segmentation clustering tasks, where the classes consist of a large number of
      distinct sub-classes. It is shown that the SOLNN clustering performance and node
      utilisation are both improved by virtue of the distribution constraint mechanism.
      The clustering results are supported by means of a detailed analysis of the
      characteristics of each pattern space. This analysis, coupled with comparative
      results obtained using other self-organising models, illustrates that the SOLNN
      clusters the patterns in accordance to the pattern space characteristics and thus
      is well-suited to clustering complex datasets.

PMID- 10939343
TI  - Complex-valued minimal resource allocation network for nonlinear signal
      processing.
AB  - This paper presents a sequential learning algorithm and evaluates its performance
      on complex valued signal processing problems. The algorithm is referred to as
      Complex Minimal Resource Allocation Network (CMRAN) algorithm and it is an
      extension of the MRAN algorithm originally developed for online learning in real
      valued RBF networks. CMRAN has the ability to grow and prune the (complex) RBF
      network's hidden neurons to ensure a parsimonious network structure. The
      performance of the learning algorithm is illustrated using two applications from
      signal processing of communication systems. The first application considers
      identification of a nonlinear complex channel. The second application considers
      the use of CMRAN to QAM digital channel equalization problems. Simulation results
      presented clearly show that CMRAN is very effective in modeling and equalization
      with performance achieved often being superior to that of some of the well known
      methods.

PMID- 10939345
TI  - Higherorder neural network group models for financial simulation.
AB  - Real world financial data is often discontinuous and non-smooth. If we attempt to
      use neural networks to simulate such functions, then accuracy will be a problem.
      Neural network group models perform this function much better. Both Polynomial
      Higher Order Neural network Group (PHONG) and Trigonometric polynomial Higher
      Order Neural network Group (THONG) models are developed. These HONG models are
      open box, convergent models capable of approximating any kind of piecewise
      continuous function, to any degree of accuracy. Moreover they are capable of
      handling higher frequency, higher order non-linear and discontinuous data.
      Results obtained using a Higher Order Neural network Group financial simulator
      are presented, which confirm that HONG group models converge without difficulty,
      and are considerably more accurate than neural network models (more specifically,
      around twice as good for prediction, and a factor of four improvement in the case
      of simulation).

PMID- 10939346
TI  - Radical pruning: a method to construct skeleton radial basis function networks.
AB  - Trained radial basis function networks are well-suited for use in extracting
      rules and explanations because they contain a set of locally tuned units.
      However, for rule extraction to be useful, these networks must first be pruned to
      eliminate unnecessary weights. The pruning algorithm cannot search the network
      exhaustively because of the computational effort involved. It is shown that using
      multiple pruning methods with smart ordering of the pruning candidates, the
      number of weights in a radial basis function network can be reduced to a small
      fraction of the original number. The complexity of the pruning algorithm is
      quadratic (instead of exponential) in the number of network weights. Pruning
      performance is shown using a variety of benchmark problems from the University of
      California, Irvine machine learning database.

PMID- 10939347
TI  - Cleavage specificity of cucumisin, a serine protease, with synthetic substrates.
AB  - The substrate specificity of a plant serine protease, cucumisin (EC 3.4.21.25),
      was studied by the use of synthetic oligopeptides and peptidyl-pNA substrates.
      Since P1'-Ser, Ala, and Gly substrates were hydrolyzed rapidly, cucumisin appears
      to prefer a small side chain at the P1' position of the oligopeptide substrate.
      The k(cat)/Km for the hydrolysis of P1-Leu, Ala, Phe, and Glu substrates
      demonstrated that they were preferentially cleaved over P1-Lys, diaminopropionic
      acid (Dap), Gly, Val, and Pro substrates. From the digestion of peptidyl-pNAs,
      the specificity of the protease was determined to be broad, but the preferential
      cleavage sites were hydrophobic amino acid residues at the P1 position.

PMID- 10939348
TI  - Microbial transformation of dehydropinguisenol by Aspergillus sp.
AB  - Two metabolites were obtained by microbial transformation of a
      furanosesquiterpene alcohol, dehydropinguisenol, using Aspergillus niger and
      Aspergillus cellulosae. Their structures were established as 10-oxo
      lejeuneapinguisenol and lejeuneapinguisenol on the basis of their spectroscopic
      data. The latter compound was obtained after 4 and 9 days of incubation with A.
      cellulosae at 30 degrees C and 25 degrees C, respectively. Aspergillus niger
      produced both metabolites after 3 and 5 days incubation at 30 degrees C,
      respectively. A possible pathway for the formation of these compounds is
      discussed here together with their antimicrobial activity against A. niger and A.
      cellulosae.

PMID- 10939349
TI  - Acyl lipid composition variation related to culture age and nitrogen
      concentration in continuous culture of the microalga Phaeodactylum tricornutum.
AB  - The influence of culture age and nitrogen concentration on the distribution of
      fatty acids among the different acyl lipid classes has been studied in continuous
      cultures of the microalga Phaeodactylum tricornutum. The culture age was tested
      in the range of 1.15-7 days, controlled by adjusting the dilution rate of fresh
      medium supplied. The effect of nitrogen concentration was tested from saturating
      conditions to starvation by modifying nitrate concentration in the fresh medium.
      Culture age had almost no influence on the fatty acid content; 16:0, 16:3 and
      20:5 increased moderately wherein the level of 16:1 decreased when the culture
      age decreased. Culture age had no effect on the total fatty acid content that
      remained around 11% of dry weight. Conversely, culture age had a greater impact
      on lipid classes, producing changes in amounts of triacylglycerols (TAG) which
      ranged between 43% and 69%, and galactolipids (GLs) that oscillated between 20%
      and 40%. In general, the content of polar lipids of the biomass decreased with
      culture age. The other factor assayed, nitrogen content, affected the fatty acid
      profile. Saturated and monounsaturated fatty acids accumulated when the nitrogen
      concentration was decreased. The experiments regarding the effect of nitrogen
      concentration on lipid species were carried out with cells of an average age of
      3.5 days. A decrease of the nitrogen concentration caused the GL fraction to
      decrease from 21 to 12%. Conversely, both neutral lipids (NLs) and phospolipids
      (PLs) increased from about 73 to 79% and from 6 to 8%, respectively. In these
      experiments, TAG was the lipid class with the highest increase, from 69 to 75%.

PMID- 10939350
TI  - Secondary products in mycorrhizal roots of tobacco and tomato.
AB  - Colonization of the roots of various tobacco species and cultivars (Nicotiana
      glauca Grah., N. longiflora Cav., N. rustica L., N. tabacum L., N. tabacum L. cv.
      Samsun NN, N. sanderae hort. Sander ex Wats.) as well as tomato plants
      (Lycopersicon esculentum L. cv. Moneymaker) by the arbuscular mycorrhizal fungus
      Glomus intraradices Schenck and Smith resulted in the accumulation of several
      glycosylated C13 cyclohexenone derivatives. Eight derivatives were isolated from
      the mycorrhizal roots by preparative high performance liquid chromatography
      (HPLC) and spectroscopically identified (MS and NMR) as mono-, di- and
      triglucosides of 6-(9-hydroxybutyl)-1,1,5-trimethyl-4-cyclohexen-3-one and
      monoglucosides of 6-(9-hydroxybutyl)-1,5-dimethyl-4-cyclohexen-3-one-1-carboxylic
      acid and 6-(9-hydroxybutyl)-1,1-dimethyl-4-cyclohexen-3-one-5-carboxylic acid. In
      contrast to the induced cyclohexenone derivatives, accumulation of the coumarins
      scopoletin and its glucoside (scopolin) in roots of N. glauca Grah. and N.
      tabacum L. cv. Samsun NN, was markedly suppressed.

PMID- 10939351
TI  - Inhibition of enzymatic browning and protection of sulfhydryl enzymes by thiol
      compounds.
AB  - In a reaction between (-)-epicatechin (EC) and 2-mercaptoethanol (2ME), catalyzed
      by partially purified polyphenol oxidase (PPO) extracted from the style of
      Rhododendron mucronatum, 2'-(2-hydroxyethylthio)-(-)-epicatechin (2'-HETEC), 5'
      (2-hydroxyethylthio)-(-)-epicatechin (5'-HETEC), and 2',5'-bis(2
      hydroxyethylthio)-(-)-epicatechin (2',5'-HETEC) were formed. The rate of
      formation of 2',5'-HETEC from 5'-HETEC was faster than that from 2'-HETEC. In the
      absence of 2ME, the concentration of EC decreased rapidly and the reaction
      mixture turned brown; 2'-, 5'-, and 2',5'-HETEC, especially 2'-substituted
      HETECs. reacted more slowly. These data indicate that 2ME acts both as an
      inhibitor of the polymerization of O-quinone, presumably by binding to it and as
      a reductant involved in the conversion of O-quinone to O-dihydroxyphenol,
      Inhibition of enzymatic browning by other thiol compounds such as cysteine and
      dithiothreitol was also investigated.

PMID- 10939352
TI  - Potato micro-tuber inducing hydroxylasiodiplodins from Lasiodiplodia theobromae.
AB  - Three hydroxylasiodiplodins were isolated from the mycelium extracts of
      Lasiodiplodia theobromae IFO 31059; and their structures were identified as
      (3R),(4S)-4-hydroxylasiodiplodin, (3R),(6R)-6-hydroxy-de-O-methyllasiodiplodin
      and (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin. All showed potato micro-tuber
      inducing activity.

PMID- 10939353
TI  - Differences in the floral anthocyanin content of red petunias and Petunia
      exserta.
AB  - In order to resolve a conflict between previous papers regarding the floral
      anthocyanins of red flowers of Petunia exserta, a naturally occurring species,
      the HPLC profile of this species was compared with that of commercial red garden
      petunias. Both HPLC profiles extremely superficially resemble each other in terms
      of relative amounts and retention times of the major anthocyanins. However, co
      elution on HPLC of the mixed sample resulted in clear separation of the
      components. Three major anthocyanins in red petunias were determined to be
      cyanidin 3-sophoroside, cyanidin 3-glucoside and peonidin 3-glucoside, which
      exhibited similar behaviors on HPLC to delphinidin 3-glucoside. delphinidin-3
      rutinoside and petunidin 3-rutinoside, respectively, the major floral
      anthocyanins of P. exserta.

PMID- 10939354
TI  - Neuroprotective phenylpropanoid esters of rhamnose isolated from roots of
      Scrophularia buergeriana.
AB  - Four phenylpropanoid esters of rhamnose, buergerisides A1, B1, B2 and C1 were
      isolated from roots of Scrophularia huergeriana MIQ. (Scrophulariaceae), and were
      characterized as 2-O-acetyl-3,4-di-O-(E)-p-methoxycinnamoyl-alpha-L
      rhamnopyranosid e, 2-O-acetyl-3-O-(E)-p-methoxycinnamoyl-alpha-L
      rhamnopyranoside, 2-O-acetvl-3-O-(Z)-p-methoxycinnamoyl-alpha-L-rhamnopyranosi de
      and 4-O-(E)-p-methoxycinnamoyl-alpha-L-rhamnopyranoside, respectively. In
      addition, six known phenylpropanoids were authenticated as: (E)-cinnamic acid,
      (E)-p-methoxycinnamic acid, (E)-p-methoxycinnamic acid methyl ester, (E)-p
      coumaric acid, (E)-caffeic acid, (E)-ferulic acid and a phenylalcohol, 2-(3
      hydroxy-4-methoxyphenyl)ethanol. These ten phenylpropanoids all attenuated
      glutamate-induced neurotoxicity when added to primary cultures of rat cortical
      cells in a dose-dependent manner. These results demonstrate that phenylpropanoids
      isolated from S. buergeriana may exert significant protective effects against
      glutamate-induced neurodegeneration in primary cultures of cortical neurons.

PMID- 10939355
TI  - Secondary metabolites from a Gloeophyllum species.
AB  - Six new sesquiterpenoids, four rearranged illudalanes, one rearranged
      protoilludane and one sterpurane, were isolated from fermentations of
      Gloeophyllum sp. 97022. Their structures were elucidated by spectroscopy.
      Gloeophyllol B and C show weak antifungal activity, while 1-hydroxy-3-sterpurene
      shows weak antifungal, antibacterial and cytotoxic activities.

PMID- 10939356
TI  - Simultaneous determination of scopolamine, hyoscyamine and littorine in plants
      and different hairy root clones of Hyoscyamus muticus by micellar electrokinetic
      chromatography.
AB  - Hyoscyamus muticus hairy root clones were established following infection with
      Agrobacterium rhizogenes strains A4, LBA-9402 and 15834 and with A. tumefaciens
      strain C58C1pRTGus104. The accumulation of tropane alkaloids hyoscyamine,
      littorine and scopolamine was evaluated by micellar electrokinetic capillary
      electrophoresis. Littorine was reported for the first time in these clones as
      well as in the roots of the intact plant and confirmed by collision induced
      dissociation-mass spectrometry. Tropane alkaloid content in hairy roots was
      compared with leaves and roots of normal plants at two vegetative stages.
      Significant differences appeared between the alkaloid contents of the different
      clones. In particular, all the hairy root clones and the roots of the intact
      plant produced 1.5-3 and 4.5-9 times more littorine than scopolamine,
      respectively. The only exception was clone KB7, carrying the h6h gene, which
      overproduced scopolamine. The aerial parts of H. muticus plants did not contain
      any littorine, thus indicating different transportation or translocation
      mechanisms of the various tropane alkaloids.

PMID- 10939357
TI  - Occurrence and characterization of oils rich in gamma-linolenic acid part II:
      fatty acids and squalene from Macaronesian Echium leaves.
AB  - Leaves from 25 Macaronesian Echium (Boraginaceae) species have been surveyed for
      hydrocarbon compounds. These plants were previously reported as the major source
      of gamma-linolenic acid so far found in nature. In addition, six European Echium
      species and the common Borago officinalis have been analysed for comparative
      purposes. High squalene amounts were found in all Echium plants from the
      Macaronesia, ranging from 3.73%, in E. simplex to 20.1% in E. fastousum. Squalene
      was almost absent from all European Echium species, and the same is true for B.
      officinalis. The relatively high oil content (2.27%) in leaves of E. fastuosum
      raises the total squalene amount to about 0.46% within this tissue. The main
      fatty acid component in the leaf was alpha-linolenic acid (ALA, 18:3omega3),
      ranging in the Macaronesian Echium from 9.32% in E. acanthocarpum to 54.45% in E.
      simplex. Possible utilisation of these plants as a commercial source of squalene
      and hypotheses about its physiological role in the plant are discussed.

PMID- 10939358
TI  - Cytotoxic cardenolides and antibacterial terpenoids from Crossopetalum gaumeri.
AB  - From the methanol extract of the roots of (Crossopetalum gaumeri, four new highly
      cytotoxic cardenolides, securigenin-3beta-O-beta-6-deoxyguloside (2), 19-hydroxy
      sarmentogenin-3beta-O-beta-6-deoxyguloside (4), sarmentogenin-3beta-O-[alpha
      allosyl-(1-->4)-beta-6-deoxy alloside] (5), and securigenin-3beta-O-[alpha
      allosyl-(1-->4)-beta-6-deoxyal loside] (6) were isolated. The dichloromethane
      extract afforded the new diterpene 3,15-dihydroxy-18-norabieta-3,8,11,13-tetraene
      (7) as well as the new triterpene 2,3,7-trihydroxy-6-oxo-1,3,5(10),7-tetraene-24
      nor-friedelane-29-o ic acid methylester (11). The new terpenoids lack
      cytotoxicity and the antibacterial activity is moderate to low.

PMID- 10939359
TI  - The phenols and prodelphinidins of white clover flowers.
AB  - White clover flowers (Trifolium repens L.) contain an abundance of phenolics,
      namely cis- and trans-p-coumaric acid 4-O-beta-D-glucopyranoside, the 3-O-beta-D
      galactopyranosides of myricetin, quercetin and kaempferol together with two new
      derivatives namely myricetin 3-O-(6"-acetyl)-beta-D-galactopyranoside and
      kaempferol 3-O-(6"-acetyl)-beta-D-galactopyranoside. Gallocatechin,
      epigallocatechin, gallocatechin-(4alpha-8)-epigallocatechin and their
      corresponding prodelphinidin polymers were also present. The 13C-NMR spectra
      showed that the polymers consisted of only gallocatechin and epigallocatechin
      monomeric units with the latter being about twice as abundant in the extenders
      but only slightly more than that in the terminating units. The average degree of
      polymerization was estimated by 13C-NMR and ES-MS, which gave a remarkably
      consistent result of about 5.8 flavanol units.

PMID- 10939360
TI  - Liquid chromatography/electron capture atmospheric pressure chemical
      ionization/mass spectrometry: analysis of pentafluorobenzyl derivatives of
      biomolecules and drugs in the attomole range.
AB  - The corona discharge used to generate positive and negative ions under
      conventional atmospheric pressure chemical ionization conditions also provides a
      source of gas-phase electrons. This is thought to occur by displacement of
      electrons from the nitrogen sheath gas. Therefore, suitable analytes can undergo
      electron capture in the gas phase in a manner similar to that observed for gas
      chromatography/electron capture negative chemical ionization/mass spectrometry.
      This technique, which has been named electron capture atmospheric pressure
      chemical ionization/mass spectrometry, provided an increase in sensitivity of 2
      orders of magnitude when compared with conventional atmospheric pressure chemical
      ionization methodology. It is a simple procedure to tag many biomolecules and
      drugs with an electron-capturing group such as the pentafluorobenzyl moiety
      before analysis. Pentafluorobenzyl derivatives have previously been used as
      electron capturing derivatives because they undergo dissociative electron capture
      in the gas phase to generate negative ions through the loss of a
      pentafluorobenzyl radical. A similar process was found to occur under electron
      capture atmospheric pressure chemical ionization conditions. By monitoring the
      negative ions that were formed, it was possible to obtain attomole sensitivity
      for pentafluorobenzyl derivatives of a representative steroid, steroid
      metabolite, prostaglandin, thromboxane, amino acid, and DNA-adduct.

PMID- 10939361
TI  - High-throughput comprehensive peptide mapping of proteins by multiplexed
      capillary electrophoresis.
AB  - A novel multimodal method for peptide mapping of proteins by multiplexed
      capillary electrophoresis (CE) is presented. By combining charge to size
      separations in four different channels and micellar electrokinetic chromatography
      for hydrophobicity-based separations in two different channels in a 96-capillary
      array, peptide fragments of digested proteins were readily resolved and showed
      unique fingerprints. Each capillary spanned several diodes in a photodiode array
      (PDA) for absorption measurement. The 96 capillaries were monitored
      simultaneously at 214 nm by a single PDA element with 1,024 diodes, and analysis
      was completed within 45 min. This demonstrates that it is possible to rapidly
      screen biotechnological products as well as to efficiently optimize separation
      conditions in CE by a combinatorial approach.

PMID- 10939363
TI  - Turn geometry for minimizing band broadening in microfabricated capillary
      electrophoresis channels.
AB  - Turns in microfabricated capillary electrophoresis channels generally result in
      degraded separation quality. To circumvent this limitation, channels were
      constructed with different types of turns to determine the design that minimizes
      turn-induced band broadening. In particular, tapered turns were created by
      narrowing the separation channel width before the start of a turn and widening
      the channel after the turn is complete. The radius of curvature of the turn, the
      length over which the channel is tapered, and the degree of tapering were
      explored. The column efficiencies were determined by examining the resolution of
      the 271/281 base pair doublet in the separation of a phiX174 HaeIII DNA sizing
      ladder. Tapered turns with the smallest radius of curvature (250 microm), the
      shortest tapering length between the separation and turn widths (55 microm), and
      the largest tapering ratio (4:1 separation channel width to turn channel width)
      produced the highest resolution separations. These results are discussed by
      comparison to theoretical predictions of the effect of tapers and turns on
      analyte band dispersion in capillary electrophoresis.

PMID- 10939362
TI  - Capillary electrochromatography of proteins on an anion-exchanger column.
AB  - Capillary electrochromatography (CEC) of proteins was carried out using 50-microm
      i.d. fused-silica capillaries packed with 5-microm silica beads having strong
      anion-exchanger functions attached to hydrophilic spacers at the chromatographic
      surface. The siliceous microspheres and the capillary innerwall were treated
      first with a heterobifunctional silanizing agent and reacted subsequently with a
      vinyl monomer containing quaternary ammonium groups to form a "tentacular" anion
      exchanger. A mixture of bovine carbonic anhydrase, alpha-lactalbumin, soybean
      trypsin inhibitor, and ovalbumin was separated using CEC by isocratic elution in
      the codirectional mode with aqueous phosphate buffer, pH 7.0, containing sodium
      chloride. The retention mechanism of isocratic CEC for proteins on the anion
      exchanger column was illustrated by the results of a study on the effect of salt
      concentration on the separation. The potential of CEC for protein separation with
      high resolution was also demonstrated by electrochromatograms of conalbumin and
      hemoglobin variants. The results shed light on the mechanism of protein
      separation by isocratic CEC, which is believed to be a combination of
      chromatographic retention by electrostatic interactions and electrophoretic
      migration. Assuming that the contributions of the two mechanisms to the overall
      migration velocity are additive, an electrochromatographic resolution equation
      was derived and compared to the resolution equation in HPLC to reveal the
      constituents responsible for the enhancement of resolution by CEC with respect to
      that in HPLC. The advantage of CEC was also examined by comparing peak capacities
      in CEC on an, isocratic platform with peak capacities obtained with isocratic and
      gradient elution HPLC.

PMID- 10939364
TI  - Coupling photochemical reaction detection based on singlet oxygen sensitization
      to capillary electrochromatography
AB  - Despite the impressive separation efficiency afforded by capillary
      electrochromatography (CEC), the detection of UV-absorbing compounds following
      separation in capillary dimensions remains limited by the short path length (5-75
      microm) through the column. Moreover, analytes that are poor chromophores present
      an additional challenge with respect to sensitive detection in CEC. This paper
      illustrates a new photochemical reaction detection scheme for CEC that takes
      advantage of the catalytic nature of type II photooxidation reactions. The
      sensitive detection scheme is selective toward molecules capable of
      photosensitizing the formation of singlet molecular oxygen (1O2). Following
      separation by CEC, UV-absorbing analytes promote groundstate 3O2 to an excited
      state (1O2) which reacts rapidly with tert-butyl-3,4,5
      trimethylpyrrolecarboxylate, which is added to the running buffer. Detection is
      based on the loss of pyrrole. The reaction is catalytic in nature since one
      analyte molecule may absorb light many times, producing large amounts of 1O2. The
      detection limit for 9-acetylanthracene, following separation by CEC, is
      approximately 6 x 10(-9) M (S/N = 3). Optimization of the factors effecting the
      S/N for four model compounds is discussed.

PMID- 10939365
TI  - A chromatographic technique to investigate the lability of copper complexes under
      steady-state conditions using high specific activity 64Cu
AB  - A novel chromatographic technique is described which has prospects for studying
      the lability of a metal complex in an aqueous system. It is based on interactions
      of metal species with an ion-exchange column under steady-state conditions. For
      this purpose, the column is equilibrated with the sample itself by using it as
      the mobile phase. With the aid of a high specific activity radiotracer, the
      characteristics of the metal species interaction with the ion-exchange column can
      be visualized in a radiochromatogram. Under particular experimental conditions,
      information regarding the dissociation kinetics of the metal complex can be
      extracted from this radiochromatogram. Erroneous results due to undesirable
      interactions of metal species with the chromatographic system are prevented,
      since the system remains in constant chemical equilibrium with the sample to be
      analyzed. The potential of this technique was investigated with copper complexes,
      using high specific activity 64Cu for labeling. Preliminary results obtained with
      four complexes (Cu-EDTA, Cu-NTA, Cu-citrate, and Cu-glycine) are discussed. For
      three complexes, dissociation rate constants could be determined: (6.2 +/- 0.3) x
      10(-3) s(-1) for Cu-EDTA, (1.0 +/- 0.04) x 10(-2) s(-1) for Cu-NTA, and (3.1 +/-
      0.2) x 10(-2) s(-1) for Cu-citrate. No dissociation rate constant could be
      determined for Cu-glycine owing to incompatible experimental conditions.

PMID- 10939366
TI  - Hot phosphate-buffered water extraction coupled on-line with liquid
      chromatography/mass spectrometry for analyzing contaminants in soil.
AB  - We evaluated the feasibility of analyzing rapidly traces of polar and medium
      polar contaminants in soil by coupling on-line a hot phosphate-buffered water
      extraction apparatus to a liquid chromatography/mass spectrometer system.
      Coupling was accomplished by using a small C-18 sorbent trap for collecting
      analytes and two six-port valves. The efficiency of this device was evaluated by
      extracting 13 selected pesticides from 200 mg of laboratory-aged soils by varying
      the extraction temperature, the extractant volume, and the flow rate at which the
      extractant passed through the extraction cell and the sorbent trap. In terms of
      extraction efficiency, robustness of the method, and extraction time, the best
      compromise was that of using 8 mL of extractant at 90 degrees C and 0.5 mL/min
      flow rate. Under these conditions, recoveries of 11 out of 13 analytes ranged
      between 82 and 103%, while those of the least hydrophilic pesticides, i.e.,
      neburon and prochloraz, were 73 and 63%, respectively. By increasing the
      extractant volume to 60 mL, additional amounts of the two latter compounds could
      be recovered. Under this condition, however, the most hydrophilic analytes were
      in part no more retained by the C-18 sorbent trap. From a naturally 1.5-year aged
      soil, hot phosphate-buffered water removed larger amounts of three herbicides and
      hydroxyterbuthylazine (a terbuthylazine degradation product) than pure water and
      Soxhlet extraction. This result seems to confirm that hot phosphate buffer is
      also able to remove from soil those fractions of contaminants that, on aging, are
      sequestered into the humic acid framework.

PMID- 10939367
TI  - Chiral gas chromatographic separation of 2-oxabicyclo[3.3.0]octane derivatives
      and their synthetic precursors.
AB  - Chiral GC separation of (+/-)-2-allyl-2-carboethoxycyclopentanone (9) and the
      alcohols (+/-)-3-(hydroxymethyl)-5-carboethoxy-2-oxabicyclo[3.3.0]octane (7), (+/
      )-2-allyl-2-carboethoxycyclopentanol (8), and their acetylated and
      trifluoroacetylated derivatives were investigated on three derivatized beta
      cyclodextrins (CDs) diluted in SE-54 or 1701-OH: 2,3,6-tri-O-methyl-beta-CD
      (PMCD); 2,3-di-O-methyl-6-O-(tert-butyldimethylsilyl)-beta-CD (DIMETBCD); 2,3-di
      O-acetyl-6-O-(tert-butyldimethylsilyl)-beta-CD (DIACTBCD). The understanding of
      these chiral separations is extremely relevant, since cyclopentanic and bicyclic
      cyclopentanic rings are common structural features of many important natural
      products and new pharmaceutical drugs. In general DIMETBCD diluted in SE-54
      showed the best chiral resolution to alcohols 7 and 8 and only DIACTBCD showed
      enantioselectivity to 9. Hydrogen bonds prediction and dipole moments data were
      obtained by molecular modeling calculations for 7ab and 8ab and Ac and TFA
      derivatives. Comparison of these data with the chromatographic parameters for the
      related compounds were used to explain the differences of their elution orders
      and diastereo- and enantiomeric separations on the above chiral stationary phases
      (CSPs). The results suggest that the CSPs enantioselectivities are not affected
      by the carboethoxy-functionalized cyclopentanic and bicyclic cyclopentanic rings
      themselves but mainly by the functional group on the other stereogenic center.

PMID- 10939368
TI  - Hihg-speed GC/MS of gasoline-range hydrocarbon compounds using a pressure-tunable
      column ensemble and time-of-flight detection
AB  - A pressure-tunable series-coupled ensemble of two capillary GC columns is
      combined with a time-of-flight MS detector for the high-speed characterization of
      mixtures containing hydrocarbon compounds. The column ensemble consists of a
      nonpolar 5% phenyl poly(dimethylsiloxane) column and a very polar poly(ethylene
      glycol) column. The TOFMS instrument uses time-array detection to obtain up to
      500 complete electron mass spectra per second. Instrument software allows for
      automated peak finding and the spectral deconvolution of severely overlapping
      unknown chromatographic peaks, if their fragmentation patterns are significantly
      different and if at least two spectra can be recorded between the peak apexes. By
      adjusting the carrier-gas pressure at the column-junction point, the separations
      between adjacent peak pairs can be adjusted to enhance the capabilities of the
      TOFMS detector. The sensitivity of peak-pair separation to changes in junction
      point pressure is studied for combinations of alkanes, olefins, and aromatic
      compounds. When complete separation is required, the use of pressure-tunable
      column ensembles cannot always provide sufficient control of peak-pair separation
      for structurally similar compounds. However, complete chromatographic separation
      typically is not required with the TOFMS detection, and a pressure-tunable column
      ensemble is very useful for the high-speed characterization of hydrocarbon
      mixtures.

PMID- 10939369
TI  - Pressurized hot water extraction coupled on-line with LC-GC: determination of
      polyaromatic hydrocarbons in sediment.
AB  - Pressurized hot water extraction (PHWE) was directly combined with a LC-GC system
      for the determination of polyaromatic hydrocarbons (PAHs) in sediment. The
      sediment sample was first extracted with pressurized hot water, and the analytes
      were adsorbed into a solid-phase trap. The trap also functioned as a LC column,
      which removed most of the interfering matrix components. The 780-microL LC
      fraction containing the analytes was directly transferred to the GC using an on
      column interface. The whole PHWE-LC-GC analysis took place in a closed system,
      and no sample pretreatment was required. The sensitivity of the method was
      excellent due to the efficient concentration in the LC-GC system. Sensitivity was
      approximately 800 times better than in traditional systems. In addition, only a
      small amount of sample (10 mg) was required for the analysis. The PHWE-LC-GC
      method proved to be linear in the concentration range of 0.01-2 microg/g, the
      limits of quantification were below 0.01 microg/g for all the analytes, and the
      relative standard deviations were between 3 and 28%. LC cleanup and the improved
      sensitivity made detection with FID sufficient for the determination of analytes.
      The results were comparable to those obtained in an interlaboratory comparison
      study as well as to the results obtained with off-line SFE-GC-MS.

PMID- 10939370
TI  - Sample preparation based on dynamic ion-exchange solid-phase extraction for GC/MS
      analysis of acidic herbicides in environmental waters.
AB  - The newly established enrichment technique, dynamic ion-exchange solid-phase
      extraction (DIE-SPE), was studied for sample preparation for GC/MS analysis of 16
      acidic herbicides in environmental waters. C18 bonded silica was the solid-phase
      material used. The optimal sample pH was weakly acidic to neutral. However, for
      common tap water and surface water, which run pH 6-9, all the acidic herbicides
      except for Chloramben could be effectively extracted from a sample of 1,000-mL
      volume without pH adjustment. The humic acid could be concurrently extracted from
      water, but most of it was separated from the sample by using 3 mL of 10% methanol
      in acetone as the eluent, which would completely elute the analytes and leave a
      large part of the humic acid on the cartridge. The selective elution reduced the
      interference of humic acid and made the DIE-SPE an effective approach for the
      analysis of the acidic herbicides in surface water. Comparing DIE-SPE with
      conventional reversed-phase SPE (RP-SPE), the former gave higher recoveries for
      the acidic herbicides and was less affected by sample matrixes. A tandem
      cartridge system combining RP- and DIE-SPE in sequence was set up for the
      simultaneous isolation of the acidic herbicides and removal of the interfering
      substances. Despite some minimal retention on the upper RP-SPE cartridge, most of
      the acidic herbicides could be extracted on the lower DIE-SPE cartridge with
      recovery over 80% except for Chloramben (50%), fenoprop (73%), MCPB (67%), and
      2,4-DB (70%) when a 500-mL aqueous sample of pH 9.5 was percolated through the
      tandem-cartridge system. The effectiveness of the system in removing the long
      carbon chain fatty acids as well as the basic and neutral organic interfering
      substances from the sample was also demonstrated.

PMID- 10939371
TI  - SFE-GC with quantitative transfer of the extraction effluent to a megabore
      capillary column
AB  - Supercritical fluid extraction was directly coupled with gas chromatography such
      that the entire extraction effluent was directed onto the GC column. A sealed
      connection between the restrictor and the column ensured that no loss of analyte
      could occur. The elevated pressure generated in the column itself resulted in a
      reduced flow rate through the column, making efficient trapping possible. Metal
      jacketed capillary columns were used as they can tolerate the elevated pressures
      required. In addition to maximizing sensitivity, very practical extraction
      parameters were possible. For a 25-min extraction, with a 2.2 mL/min flow rate,
      and the column at 40 degrees C, analytes as volatile as C-14 were trapped and
      separated. Trapping efficiency improved further with shorter extraction times,
      mild cooling of the column, or lower flow rates.

PMID- 10939372
TI  - Identification and quantification of 77 pesticides in groundwater using solid
      phase coupled to liquid-liquid microextraction and reversed-phase liquid
      chromatography.
AB  - This paper describes a method for the extraction, separation, identification, and
      quantification of 77 pesticides (neutral, acidic, and basic) including some s
      triazine metabolites. The method is appropriate for organically (e.g. with humic
      acids) highly loaded groundwater samples. A comparative study of a pH-controlled
      mixed solid phase (LiChroprep RP18/LiChrolut EN) extraction with different
      desorption solvents (acetonitrile or acetonitrile and dichloromethane/methanol)
      is elaborated. A subsequent liquid-liquid microextraction reduces matrix effects.
      The pesticides in the sample are separated using RP-HPLC, detected, and
      identified by diode array. The efficiency is illustrated on a natural groundwater
      sample from a phreatic aquifer.

PMID- 10939373
TI  - Performance-enhanced "tunable" capillary microwave-induced plasma mass
      spectrometer for gas chromatography detection.
AB  - Improvements in the stability and performance of a capillary microwave-induced
      plasma-mass spectrometer (MIP-MS) were achieved by optimizing power transfer to
      the cavity using a tunable coaxial MIP. The MIP, operating at atmospheric
      pressure, was sustained with 30 mL/min He and 60 W of power. Measurement
      precision and sensitivity for the standard waveguide and coaxial systems were
      determined using 16 organochlorine pesticide solutions separated by gas
      chromatography (GC). The linear dynamic range obtained with the tunable MIP-MS
      extended over 3 orders of magnitude, a 10 time improvement with respect to the
      standard MIP. Detection limits were between 3 and 19 pg of Cl mol(-1) s(-1), 7
      times lower than the detection limits obtained with the nontunable MIP-MS.
      Analysis of pesticides containing sulfur atoms was also possible, further
      demonstrating multielement MIP-MS detection. Excellent accuracy (10% recovery)
      and precision (5% RSD) were found for the detection of the pesticides in a
      petroleum-contaminated reference soil. By placing the GC column at the plasma
      expansion stage, molecular fragmentation of a mixture of volatile organic
      compounds was also demonstrated. With the MS operated in the selected ion
      monitoring mode, measurement sensitivity was approximately 500 pg/s per compound.

PMID- 10939375
TI  - Alkaline CuO oxidation with a microwave digestion system: lignin analyses of
      geochemical samples.
AB  - A novel approach for the analysis of lignin in geochemical samples has been
      developed as an alternative to the alkaline CuO oxidation procedure first
      developed in 1982. The new procedure utilizes microwave digestion technology, as
      opposed to conductive heating, to carry out oxidative hydrolysis of six samples
      in an oxygen-free atmosphere at 150 degrees C for 90 min. Ethyl acetate is used
      as the extraction solvent in place of diethyl ether. Additionally, the new method
      incorporates a simplified extraction procedure that minimizes solvent handling
      and the amount of glassware needed. Under these novel conditions, the yields and
      compositions of lignin phenols from four different samples (modern and ancient
      sediments; woody and nonwoody tissues) match those obtained by the "traditional"
      procedure. The significant advantages of this new alkaline CuO oxidation method
      include faster reaction times, the ability to accurately measure and control
      reaction conditions, added flexibility for the analyst, and a marked increase in
      the achievable sample throughput.

PMID- 10939374
TI  - Equilibrium and kinetic measurements of muscarinic receptor antagonism on living
      cells using bead injection spectroscopy.
AB  - Bead injection spectroscopy (BIS) techniques are introduced for automated
      measurement of pharmacological antagonism by functional assay. Chinese hamster
      ovary cells that express the rat type 1 muscarinic receptor are cultured on
      microbeads and used as a renewable biological target for muscarinic receptor
      antagonist ligands. A flow injection instrument is used to reproducibly sample
      and capture the cells in a jet ring chamber. The effect of the antagonist
      pirenzepine on the carbachol-induced intracellular calcium response of the cells
      is measured with a fluorescence microscope photometry system. The BIS functional
      assay is used to quantify both equilibrium and kinetic pharmacological values for
      pirenzepine. In addition, two muscarinic receptor antagonists (pirenzepine and
      atropine) are assayed to compare their relative efficacy at diminishing the
      calcium response. Due to the precision of the automated fluid/bead handling
      protocols, and reproducibility of the measured calcium response, the
      quantification of useful pharmacological information from living cells by BIS
      techniques is demonstrated.

PMID- 10939376
TI  - Imaging size-selective permeation through micropatterned thin films using
      scanning electrochemical microscopy
AB  - This paper describes a new approach for quantification of rates of molecular
      transport through patterned, or otherwise heterogeneous, porous films supported
      on conductive substrates. Scanning Electrochemical Microscopy (SECM) has been
      used to image molecular sieving of redox active probes by thin,
      electropolymerized films of Fe(5-amino-1,10-phenanthroline)3(2+) on
      micropatterned and microdisk array electrodes. Films as thin as 12 nm completely
      block redox mediators with average molecular diameters greater than 12 A, whereas
      smaller diameter probes (radii 5-8 A) were observed to permeate selectively. SECM
      tip currents measured for three different redox permeants/mediators are observed
      to decrease with increasing polymer thickness, consistent with a transport model
      that includes partitioning into and diffusion within the polymer films.
      Permeabilities, PDf, within the poly[Fe(5-NH2-phen)3(2+)] films have been
      quantitatively determined from the SECM tip currents and are in excellent
      agreement with data previously obtained from rotatingdisk electrochemistry. This
      new methodology provides a versatile approach for quantitative investigation of
      membrane transport and permeation selectivity with good lateral spatial
      resolution.

PMID- 10939377
TI  - Optimization of high-performance DNA sequencing on short microfabricated
      electrophoretic devices.
AB  - We have examined the parametric performance of short microfabricated
      electrophoresis devices that operate with a replaceable linear poly(acrylamide)
      (LPA) solution for the application of DNA sequencing. A systematic study is
      presented of the dependence of selectivity, separation efficiency, and resolution
      of sequencing fragments on buffer composition, LPA concentration, LPA
      composition, microdevice temperature, electric field, and device length. A
      specific optimization is made for DNA sequencing on 11.5-cm devices. Using a
      separation matrix composed of 3.0% (w/w) 10 MDa plus 1.0% (w/w) 50 kDa LPA,
      elevated microdevice temperature (50 degrees C), and 200 V/cm, high-speed DNA
      sequencing of 580 bases on standard M13mp18 was obtained in only 18 min with a
      base-calling accuracy of 98.5%. Read lengths of 640 bases at 98.5% accuracy were
      achieved in approximately 30 min by reducing the electric field strength to 125
      V/cm. We believe that this constitutes matrix-limited performance for
      microdevices of this length using LPA sieving matrix and this buffer chemistry.
      In addition, it was confirmed, that shorter devices are rather impractical for
      production sequencing applications when LPA is used as sieving matrix.

PMID- 10939378
TI  - MutS-mediated detection of DNA mismatches using atomic force microscopy.
AB  - We have developed an atomic force microscopy-based method for detecting DNA base
      pair mismatches using MutS protein isolated from E. coli. MutS is a biological
      sensor and a locator of DNA base-pair mismatches. It binds specifically to a
      mismatched DNA base pair and initiates a process of DNA repair. To test the
      possibility of visually detecting mismatched base pairs by atomic force
      microscopy, we prepared DNA templates approximately 500 bp in length consisting
      of a single or multiple base-pair mismatches. We demonstrate that MutS binding
      sites on individual DNA molecules were readily detectable by atomic force
      microscopy and that the observed positions were in good agreement with the
      predicted sites of base-pair mismatches at a few-nanometer resolution. The
      technique described here is rapid and sensitive and is expected to be useful in
      screening mutations and DNA polymorphisms.

PMID- 10939379
TI  - Optical detection of polycations via polymer film-modified microtiter plates:
      response mechanism and bioanalytical applications.
AB  - Microtiter plate wells modified with thin (approximately 20 microm) polymeric
      films capable of optically sensing macromolecular protamine and other
      polycationic species are described. The plates are prepared by coating the bottom
      of each well of a conventional 96-well polypropylene plate with an adherent
      polymer film (a mixture of poly(vinyl chloride) and polyurethane) containing a
      lipophilic 2',7'-dichlorofluorescein derivative. Surprisingly, optical response
      toward polycations is shown to result from the extraction of the fluorescein
      derivative from the polymer film into a lyophobic colloidal phase at the
      sample/film interface. This new phase is likely composed of a micellular-type ion
      pair complex between the analyte polycation from aqueous sample phase and the
      deprotonated form of the fluorescein derivative. Accumulation of the deprotonated
      fluorescein species in this interfacial region induces an absorbance change
      measured at 540 nm. Optimized plates can be used to sense protamine
      concentrations in the range of 0-100 microg/mL in 10 min with little or no
      response to physiological levels of common cationic species (Na+, K+, Ca2+,
      etc.). The modified plates are shown to be useful as simple optical detectors for
      measuring heparin levels in plasma via titrations with protamine and for
      monitoring protease activities (trypsin and plasmin) that cleave polycationic
      peptides/proteins such as protamine into smaller peptide fragments that are not
      detected by the sensing films. Assays for "clot busting" plasminogen activators
      (streptokinase, urokinase, and tissue plasminogen activator) are also
      demonstrated using this relatively simple microtiter plate-based polycation
      detection system.

PMID- 10939380
TI  - Comparison and improvement of the determinations of actinide low activities using
      several alpha liquid scintillation spectrometers
AB  - We applied three procedures using two a liquid scintillation spectrometers
      (PERALS and TRI-CARB) and two scintillation cocktails (Alphaex and Ultima Gold
      LLT) for the determination of alpha-emitter low activities. For each procedure,
      the limit of detection, the resolution, the separation factor, and the Fischer
      coefficient were determined in order to perform 232U-234U-238U isotopic
      measurements. The deconvolution usually performed is clean when the PERALS
      spectrometer is used. This is not possible for the TRI-CARB spectrometer using
      the Ultima Gold LLT scintillation cocktail. This problem was solved by combining
      the advantages of both techniques using the Alphaex scintillation cocktail in the
      TRI-CARB spectrometer. Under these conditions, the limit of detection was
      improved, the resolution decreased from 500-800 to 420-590 keV, and the
      separation factor increased from 0.9 to 1.1-1.2. This third procedure was applied
      with success for 232U-234U-238U isotopic experiments.

PMID- 10939381
TI  - Fabrication of topologically complex three-dimensional microfluidic systems in
      PDMS by rapid prototyping.
AB  - This paper describes a procedure for making topologically complex three
      dimensional microfluidic channel systems in poly(dimethylsiloxane) (PDMS). This
      procedure is called the "membrane sandwich" method to suggest the structure of
      the final system: a thin membrane having channel structures molded on each face
      (and with connections between the faces) sandwiched between two thicker, flat
      slabs that provide structural support. Two "masters" are fabricated by rapid
      prototyping using two-level photolithography and replica molding. They are
      aligned face to face, under pressure, with PDMS prepolymer between them. The PDMS
      is cured thermally. The masters have complementary alignment tracks, so
      registration is straightforward. The resulting, thin PDMS membrane can be
      transferred and sealed to another membrane or slab of PDMS by a sequence of steps
      in which the two masters are removed one at a time; these steps take place
      without distortion of the features. This method can fabricate a membrane
      containing a channel that crosses over and under itself, but does not intersect
      itself and, therefore, can be fabricated in the form of any knot. It follows that
      this method can generate topologically complex microfluidic systems; this
      capability is demonstrated by the fabrication of a "basketweave" structure. By
      filling the channels and removing the membrane, complex microstructures can be
      made. Stacking and sealing more than one membrane allows even more complicated
      geometries than are possible in one membrane. A square coiled channel that
      surrounds, but does not connect to, a straight channel illustrates this type of
      complexity.

PMID- 10939382
TI  - A continuous film-recirculable drop gas-liquid equilibration device. Measurement
      of trace gaseous ammonia
AB  - A miniature gas-liquid equilibrator or a gas collector, intended as a low-volume
      interface between a soluble gaseous sample and a liquid phase analyzer or between
      a liquid phase sample and a detector designed for use with gas samples, is
      described. This paper addresses the application of the device for the measurement
      of trace atmospheric ammonia. Gas collection occurs solely by diffusive sampling
      such that aerosol particles are not collected. The device essentially consists of
      a tube surrounded externally by a jacket. Gas flows through the jacket and
      contacts a liquid film flowing on the surface of the tube. The flowing film forms
      a drop at the tube terminus and is aspirated off through the inner bore of the
      tube. The collected analyte can be (a) directly sent to an analysis system or (b)
      preconcentrated on a suitable stationary phase; the preconcentrator effluent can
      be recycled, if desired. With a fluorometric flow injection analysis system
      harnessed to measure ammonia with such a collector, the limit of detection (LOD,
      S/N = 3) for a sample drawn for 18 min at 200 mL/min was 4.5 parts per trillion
      by volume, with the linear range extending up to 30 parts per billion.

PMID- 10939383
TI  - Estimating realistic confidence intervals for the activation energy determined
      from thermoanalytical measurements
AB  - A statistical procedure is proposed for estimating realistic confidence intervals
      for the activation energy determined by using an advanced isoconversional method.
      Nine sets of five thermogravimetric measurements have been produced for the
      process of gassification of ammonium nitrate at five different heating rates.
      Independent estimates of the confidence intervals for the activation energy have
      been obtained from these data sets. Agreement with these independent estimates
      demonstrates that the proposed statistical procedure is capable of adequately
      estimating the actual uncertainty in the activation energy determined from a
      small number of measurements. The resulting averaged relative errors in the
      activation energy were found to be 26, 21, and 17% for three, four, and five
      heating rate estimates, respectively.

PMID- 10939384
TI  - Prototyping of masks, masters, and stamps/molds for soft lithography using an
      office printer and photographic reduction
AB  - This paper describes a practical method for the fabrication of photomasks,
      masters, and stamps/molds used in soft lithography that minimizes the need for
      specialized equipment. In this method, CAD files are first printed onto paper
      using an office printer with resolution of 600 dots/in. Photographic reduction of
      these printed patterns transfers the images onto 35-mm film or microfiche. These
      photographic films can be used, after development, as photomasks in 1:1 contact
      photolithography. With the resulting photoresist masters, it is straightforward
      to fabricate poly(dimethylsiloxane) (PDMS) stamps/molds for soft lithography.
      This process can generate microstructures as small as 15 microm; the overall time
      to go from CAD file to PDMS stamp is 4-24 h. Although access to equipment-spin
      coater and ultraviolet exposure tool-normally found in the clean room is still
      required, the cost of the photomask itself is small, and the time required to go
      from concept to device is short. A comparison between this method and all other
      methods that generate film-type photomasks has been performed using test patterns
      of lines, squares, and circles. Three microstructures have also been fabricated
      to demonstrate the utility of this method in practical applications.

PMID- 10939385
TI  - Preparation and properties of vapor detector arrays formed from poly(3,4
      ethylenedioxy)thiophene-poly(styrene sulfonate)/insulating polymer composites
AB  - Poly(3,4-ethylenedioxy)thiophene-poly(styrene sulfonate) (PEDOT-PSS) was used as
      the conductive component in a matrix of chemically different insulating polymers
      to form an array of vapor detectors. Such composites produced larger relative
      differential resistance responses when exposed to polar analytes than did the
      corresponding carbon black filled polymer composite detectors. However, the PEDOT
      PSS composites produced smaller responses than carbon black composites when
      exposed to nonpolar analytes. The resolving power of a PEDOT-PSS detector array
      was compared to that of a carbon black composite array for a broadly construed
      set of organic vapors. The PEDOT-PSS array exhibited better, on average,
      discrimination between pairs of polar analytes and polar/nonpolar analytes than
      did the carbon black composite array. The carbon black composite array out
      performed the PEDOT-PSS array in discriminating between nonpolar compounds. The
      addition of PEDOT-PSS composites to an array of carbon black composite detectors
      therefore can produce improved overall discrimination in a vapor sensor system
      when used in tasks to differentiate between of a broad set of analyte vapors.

PMID- 10939386
TI  - Electrocatalysis at a conducting composite electrode doped with a ruthenium(II)
      metallodendrimer.
AB  - A pentaerythritol-based metallodendrimer with RuIIterpyridine units was
      synthesized and tested as a mediator for the electrochemical oxidation of
      methionine (L-Met), cystine (L-Cys), and AsIII. A reversible oxidation of RuII
      was observed with the metallodendrimer as a solute in mixed acetonitrile-water
      solvents and as a component of carbon-based conducting composite electrodes.
      Mediated oxidation of the test species was observed. In aqueous solution, the
      composite electrode yielded a cyclic voltammetric peak current for the oxidation
      of L-Met in a 0.1 M phosphate buffer (pH 7.0) at 1.1 V vs Ag/AgCl. This anodic
      process was employed for amperometric detection in a flow system. Linear
      calibration curves were obtained over the range 1.0-10 microM Met and Cys. Using
      the criterion of the concentration yielding a signal 3 times the uncertainty of a
      blank, detection limits of 0.6 and 0.5 microM were calculated for Met and Cys,
      respectively. The slopes with three nominally identical electrodes varied by 10%.

PMID- 10939387
TI  - Dual-electrode electrochemical detection for poly(dimethylsiloxane)-fabricated
      capillary electrophoresis microchips.
AB  - The development of a poly(dimethylsiloxane)-based (PDMS-based) microchip
      electrophoresis system employing dual-electrode electrochemical detection is
      described. This is the first report of dual-electrode electrochemical detection
      in a microchip format and of electrochemical detection on chips fabricated from
      PDMS. The device described in this paper consists of a top layer of PDMS
      containing the separation and injection channels and a bottom glass layer onto
      which gold detection electrodes have been deposited. The two layers form a tight
      reversible seal, eliminating the need for high-temperature bonding, which can be
      detrimental to electrode stability. The channels can also be temporarily removed
      for cleaning, significantly extending the lifetime of the chip. The performance
      of the chip was evaluated using catechol as a test compound. The response was
      linear from 10 to 500 microM with an LOD (S/N = 3) of 4 microM and a sensitivity
      of 45.9 pA/microM. Collection efficiencies for catechol ranged from 28.7 to 25.9%
      at field strengths between 200 and 400 V/cm. Dual-electrode detection in the
      series configuration was shown to be useful for the selective monitoring of
      species undergoing chemically reversible redox reactions and for peak
      identification in the electropherogram of an unresolved mixture.

PMID- 10939389
TI  - Which of three voltammetric methods, when applied to a reversible electrode
      reaction, can best cope with double-layer capacitance and severe uncompensated
      resistance?
AB  - The presence of uncompensated resistance and double-layer capacitance confounds
      the accurate measurements of the bulk concentration of electroreactant and the
      reversible half-wave potential from an experimental voltammogram. It is pertinent
      to ask which simple voltammetric technique-chronopotentiometry, linear-scan
      voltammetry, or potential-step voltammetry-is best able to confront these
      difficulties. We have carried out a modeling study in an attempt to answer this
      question. First, we devised an exact method of simulating each variety of
      reversible voltammogram, incorporating the effects of resistance and capacitance.
      Next, we developed an unprejudiced method of analyzing these voltammograms to
      recover both electrochemical parameters. Then we performed a sensitivity analysis
      on a very large number of simulated voltammograms by measuring the apparent half
      wave potential and concentration when slightly erroneous values of resistance and
      capacitance were employed in the recovery step. Thereby we hoped to ascertain how
      uncertainty in the magnitudes of the two interfering electrical elements affects
      the measured values of the two electrochemical parameters. Basing conclusions on
      the sizes of the four sensitivity indices, we conclude, surprisingly, that linear
      scan voltammetry, not chronopotentiometry, is most often the method of choice.

PMID- 10939388
TI  - Electrocatalysis of NADH oxidation with an electropolymerized film of 1,4-bis(3,4
      dihydroxyphenyl)-2,3-dimethylbutane.
AB  - The oxidation of 1,4-bis(3,4-dihydroxyphenyl)-2,3-dimethylbutane, known also as
      nordihydroguaiaretic acid, on a glassy carbon electrode anodically pretreated in
      KCl solution gives rise to a stabile redox-active polymer containing the o
      quinone moiety. The redox response of the modified electrode is typical for a
      surface-immobilized species. The modifier thickness can be easy controlled by a
      number of potential cycles applied during electropolymerization, and a surface
      coverage up to 1.1 x 10(-9) mol cm(-2) can be achieved. The film exhibits
      catalytic activity toward NADH oxidation. Characteristic kinetic constants for
      the mediated oxidation of NADH were derived from rotating disk experiments
      performed in phosphate or Tris/acetate buffers. The effects of film thickness,
      solution pH, and the presence of Mg2+ cation on the catalytic efficiency of the
      modified electrode were discussed and compared with literature data concerning
      related systems.

PMID- 10939390
TI  - Bismuth-coated carbon electrodes for anodic stripping voltammetry
AB  - Bismuth-coated carbon electrodes display an attractive stripping voltammetric
      performance which compares favorably with that of common mercury-film electrodes.
      These bismuth-film electrodes are prepared by adding 400 microg/L (ppb)
      bismuth(III) directly to the sample solution and simultanously depositing the
      bismuth and target metals on the glassy-carbon or carbon-fiber substrate.
      Stripping voltammetric measurements of microgram per liter levels of cadmium,
      lead, thallium, and zinc in nondeaerated solutions yielded well-defined peaks,
      along with a low background, following short deposition periods. Detection limit
      of 1.1 and 0.3 ppb lead are obtained following 2- and 10-min deposition,
      respectively. Changes in the peak potentials (compared to those observed at
      mercury electrodes) offer new selectivity dimensions. Scanning electron
      microscopy sheds useful insights into the different morphologies of the bismuth
      deposits on the carbon substrates. The in situ bismuth-plated electrodes exhibit
      a wide accessible potential window (-1.2 to -0.2 V) that permits quantitation of
      most metals measured at mercury electrodes (except of copper, antimony, and
      bismuth itself). Numerous key experimental variables have been characterized and
      optimized. High reproducibility was indicated from the relative standard
      deviations (2.4 and 4.4%) for 22 repetitive measurements of 80 microg/L cadmium
      and lead, respectively. Such an attractive use of "mercury-free", environmetally
      friendly electrodes (with a performance equivalent to that of mercury ones)
      offers great promise to centralized and decentralized testing of trace metals.

PMID- 10939391
TI  - Electrogenerated chemiluminescence. 66. The role of direct coreactant oxidation
      in the ruthenium tris(2,2')bipyridyl/tripropylamine system and the effect of
      halide ions on the emission intensity
AB  - We describe the electrogenerated chemiluminescence (ECL) processes of the
      Ru(bpy)3(2+) (bpy = 2,2'-bipyridyl)/ tripropylamine (TPrA) system at glassy
      carbon, platinum, and gold electrodes. The electrochemical behavior of TPrA on
      different electrode materials and its influence on the ECL process are
      demonstrated. At glassy carbon electrodes, the direct oxidation of TPrA began at
      approximately 0.6 V vs SCE and exhibited a broad irreversible anodic peak. Two
      ECL waves were observed, one in the potential region more negative than 1.0 V vs
      SCE and one at more positive potentials. The first ECL process apparently occurs
      without the electrogeneration of Ru(bpy)3(3+), in contrast to that of the second
      ECL wave. At Pt and Au electrodes, however, the formation of surface oxides
      significantly blocked the direct oxidation of TPrA. An ECL wave below 1.0 V did
      not appear at Pt and was very weak at gold. The ECL peaks at potentials of 1.1
      1.2 V were also much weaker than those observed at the glassy carbon electrode.
      These results showed that the direct oxidation of TPrA played an important role
      in the ECL processes. Therefore, the enhancement of the TPrA oxidation current
      might lead to an increase in the ECL intensity. Small amounts of halide species
      were found to inhibit the growth of surface oxides on Pt and gold electrodes and
      led to an obvious increase of TPrA oxidation current. The anodic dissolution of
      gold in halide-containing solution was also important in activating the gold
      electrode surface. The electrochemical catalytic effect of bromide further
      promoted the oxidation of TPrA. A halide effect on ECL at Pt and Au electrodes
      was also evident. The most effective enhancement of ECL was observed at Au
      electrode in a bromide-containing solution. This effect was also found in an
      commercial flow-through instrument (IGEN) and provided a simple way to improve
      the detection sensitivity at low concentrations of Ru(bpy)3(2+).

PMID- 10939392
TI  - A bulk electrolysis Raman spectroelectrochemical cell using a rotating electrode
AB  - A fast bulk electrolysis Raman spectroelectrochemical cell is described. The cell
      employs a large-area platinum gauze and disk assembly which can be rotated at
      speeds up to 5,000 rpm. The complete electrolysis of a 5-mL solution can be
      achieved in less than 6 min using a 2,000 rpm rotation rate. The resonance Raman
      spectrum of (TPP*+)Cu(II) was collected in situ in this cell.

PMID- 10939393
TI  - Improved detection limits and unbiased selectivity coefficients obtained by using
      ion-exchange resins in the inner reference solution of ion-selective polymeric
      membrane electrodes
AB  - By using a high concentration of an interfering ion and a low one of the primary
      ion in the inner reference solution of polymeric membrane ion-selective
      electrodes (ISEs), the lower detection limit may be improved and unbiased
      thermodynamic selectivity coefficients may be obtained. To this purpose, a cation
      exchange resin is used here to keep the low concentration of the primary cation
      constant. Different compositions of the internal solution are required for
      obtaining optimal lower detection limits and unbiased selectivity coefficients.
      All ISEs studied here, i.e., for K+, Ca2+, and NH4+, based on valinomycin, ETH
      5234, and nonactin/monactin, respectively, show improved lower detection limits
      in the range of 10(-7.6) (NH4+) to 10(-8.8) M (Ca2+). Nernstian responses and,
      therefore, unbiased selectivity coefficients are obtained with the K+-ISE for the
      discriminated ions, Na+, Mg2+, and Ca2+.

PMID- 10939394
TI  - Chronopotentiometric analysis of highly resistive media
AB  - Reciprocal derivative chronopotentiometry is shown to be well suited for
      performing electrochemistry in highly resistive solutions in connection to
      conventional-sized electrodes. The fundamentally different operational principles
      of reciprocal derivative chronopotentiometry (compared to controlled-potential
      voltammetry) reduces its susceptibility to solution resistance effects. The
      influences of the electrolyte concentration and constant current upon the
      reciprocal derivative chronopotentiometric peak area and potential are examined
      in different solvents. Well-defined, analytically useful peaks are observed in
      highly resistive media (with low electrolyte/analyte ratios). Narrower peaks,
      shifted to higher potential values, are observed upon increasing the solution
      resistance. Yet, the analytical signal (square root of the peak area) is nearly
      independent of the ohmic drop. The experimental results are compared with the
      theoretical predictions. Considerable ohmic drop distortions are observed in
      analogous voltammetric experiments. The defined chronopotentiometric peaks permit
      convenient quantitation of micromolar analyte concentrations in highly resistive
      media. Such observations open the door to new electrochemical applications of
      conventional electrodes that were previously restricted to ultramicroelectrodes.

PMID- 10939395
TI  - Probing the limits: ultraslow diffusion and heterogeneous electron transfers in
      redox polyether hybrid cobalt bipyridine molten salts
AB  - This paper describes microelectrode voltammetry measurements of self-diffusion
      coefficients and of heterogeneous Co(II/III) electron-transfer rate constants
      (ko) in undiluted molten salts of three cobalt tris(bipyridine) perchlorate
      complexes in which the bipyridine ligands are "tailed" with poly(propylene oxide)
      and poly(ethylene oxide) oligomers. The self-diffusion coefficients are measured
      with potential step chronoamperometry and range from 10(-12) to 10(-17) cm2/s,
      while the quasi-reversible reaction rate constants are measured using cyclic
      voltammetry and small potential steps and range from 10(-7) to 10(-12) cm/s. The
      ko measurements are unusual in that when rate constants become smaller, the
      reaction remains quasi-reversible, because of concurrently decreasing self
      diffusion rates. The measurements are, furthermore, accomplished in the face of
      uncompensated resistances that range from mega- to gigaohms, which is made
      possible by the combination of microelectrode properties and small diffusivities.
      The melt in which self-diffusion and ko values are smallest is at a temperature
      below its nominal glassing transition and in the regime of molecule-scale
      diffusion profiles.

PMID- 10939396
TI  - Segregation of micrometer-dimension biosensor elements on a variety of substrate
      surfaces.
AB  - With the rapid development of micro total analysis systems and sensitive
      biosensing technologies, it is often desirable to immobilize biomolecules to
      small areas of surfaces other than silicon. To this end, photolithographic
      techniques were used to derivatize micrometer-sized, spatially segregated
      biosensing elements on several different substrate surfaces. Both an interference
      pattern and a dynamic confocal patterning apparatus were used to control the
      dimensions and positions of immobilized regions. In both of these methods, a UV
      laser was used to initiate attachment of a photoactive biotin molecule to the
      substrate surfaces. Once biotin was attached to a substrate, biotin/avidin/biotin
      chemistry was used to attach fluorescently labeled or nonlabeled avidin and
      biotinylated sensing elements such as biotinylated antibodies. Dimensions of 2-10
      microm were achievable with these methods. A wide variety of materials, including
      glassy carbon, quartz, acrylic, polystyrene, acetonitrile-butadiene-styrene,
      polycarbonate, and poly(dimethylsiloxane), were used as substrates. Nitrene- and
      carbene-generating photolinkers were investigated to achieve the most homogeneous
      films. These techniques were applied to create a prototype microfluidic sensor
      device that was used to separate fluorescently labeled secondary antibodies.

PMID- 10939397
TI  - Hydrodynamic flow profiling in microchannel structures by single molecule
      fluorescence correlation spectroscopy
AB  - In this paper we demonstrate high spatial resolution hydrodynamic flow profiling
      in silicon wafer based microchannels using single molecule fluorescence
      correlation spectroscopy (FCS). We have used confocal fluorescence microscopy to
      detect single tetramethylrhodamine (TMR-4-dUTP) biomolecules traversing a
      approximately 1 fL volume element defined by an argon laser beam focus. By
      elevating a (approximately 10(-10) M) reservoir of diluted analyte, a continuous
      hydrodynamic flow through the microstructure could be accomplished. The
      microchannel was then scanned with a diffraction-limited focus in approximately 1
      microm steps in both the vertical and the horizontal directions to determine the
      flow profile across a 50 x 50 microm2 channel. The flow profile measured was
      parabolic in both dimensions, thereby showing a Poiseuille laminar flow profile.
      Future microstructures can hereby be nondestructively investigated with the use
      of high spatial resolution confocal correlation microscopy.

PMID- 10939399
TI  - A cluster expansion method for the complete resolution of microscopic ionization
      equilibria from NMR titrations
AB  - The NMR chemical shift of spin 1/2 nuclei in a polyprotic molecule represents a
      sensitive probe of microscopic protonation equilibria. However, these equilibria
      are commonly parametrized in terms of microscopic equilibrium constants, whose
      number increases very rapidly with the number of ionizable groups. For that
      reason their determination was considered to be basically impossible except for
      the cases of the simplest molecules. On the basis of a cluster expansion of the
      free energy of a microstate, we propose a novel parametrization of this problem
      that drastically reduces the number of necessary parameters needed to specify the
      microscopic equilibria. Such cluster parameters can be extracted from NMR
      titration data in a straightforward way. Once these parameters are known, all
      microscopic equilibrium constants can be obtained.

PMID- 10939398
TI  - Liquid chromatography/electrospray mass spectrometry of organoselenium compounds
      with postcolumn crown ether complexation.
AB  - Postcolumn addition is an effective means of alleviating or solving ionization
      related problems in liquid chromatography/electrospray ionization mass
      spectrometry (LC/ESIMS). In the current study, initial attempts to develop a
      direct LC/ESIMS method for an organoselenium compound, 4-hydroxyphenyl 2-methyl-2
      aminoethyl selenide (HOMePAESe), were unsuccessful because of extensive
      fragmentation which occurred even under the mildest in-source collision-induced
      dissociation (CID) conditions. To reduce the extent of compound fragmentation, a
      crown ether, 18-crown-6, was added postcolumn to the system, forming a complex
      with HOMePAESe, which survived the electrospray ionization process with reduced
      fragmentation and hence improved sensitivity for the major ions. The general
      applicability of this crown ether complexation approach to clinical samples was
      demonstrated by the analysis of HOMePAESe in human urine, using a structural
      analogue, 4-fluorophenyl 2-aminoethyl selenide (FPAESe) as an internal standard.
      The limit of detection for HOMePAESe, based on a signal-to-noise ratio of 3:1,
      was estimated to be 5 pg/microL in urine. The potential application of this
      approach to the general analysis of other amine-containing compounds was also
      evaluated.

PMID- 10939400
TI  - Using molecular beacons to probe molecular interactions between lactate
      dehydrogenase and single-stranded DNA.
AB  - The interactions between two key macromolecular species, nucleic acids and
      proteins, control many important biological processes. There have been limited
      effective methodologies to study these interactions in real time. In this work,
      we have applied a newly developed molecular beacon (MB) DNA probe for the
      analysis of an enzyme, lactate dehydrogenase (LDH), and for the investigation of
      its properties of binding with single-stranded DNA. Molecular beacons are single
      stranded oligonucleotide probes designed to report the presence of specific
      complementary nucleic acids by fluorescence detection. The interaction between
      LDH and MB has resulted in a significant fluorescence signal enhancement, which
      is used for the elucidation of MB/LDH binding properties. The processes of
      binding between MB and different isoenzymes of LDH have been studied. The results
      show that the stoichiometry of LDH-5/MB binding is 1:1, and the binding constant
      is 1.9 x 10(-7) M(-1). We have also studied salt effects, binding sites,
      temperature effects, pH effects, and the binding specificities for different
      isoenzymes. Our results demonstrate that MB can be effectively used for sensitive
      protein quantitation and for efficient protein-DNA interaction studies. MB has a
      signal transduction mechanism built within the molecule and can thus be used for
      the development of rapid protein assays and for real-time measurements.

PMID- 10939402
TI  - A parallel miniature cylindrical ion trap array
AB  - A small mass spectrometer array is described in which each element is a
      cylindrical ion trap (CIT). The array contains four CITs, each having an inner
      radius of 2.5 mm, arranged in parallel and operated using a single electronics
      system under common conditions for trapping and mass analysis. By using an array
      of identically sized traps, higher ion capacity can be achieved than with a
      single miniature CIT, but the advantage of lower power and voltage requirements
      associated with the smaller ion trap is maintained. Overall signal intensity of
      the array of four traps is compared with that of a two-element CIT array to
      demonstrate the increased ion capacity of larger arrays. Resolution for m
      dichlorobenzene is shown to be approximately 180 (full width at half-maximum),
      with no significant loss in resolution as a result of using multiple CITs. The
      detection of 5 x 10(-9) Torr partial pressure of krypton in argon with a signal
      to-noise ratio of approximately 30 for the most abundant isotope is shown,
      demonstrating the applicability of the device for process gas monitoring. Also, a
      preliminary spectrum from a 10-CIT array with each element having an inner radius
      of 1.5 mm is reported.

PMID- 10939401
TI  - Molecularly imprinted fluorescent-shift receptors prepared with 2
      (trifluoromethyl)acrylic acid.
AB  - Methacrylic acid (MAA) and 2-(trifluoromethyl)acrylic acid (TFMAA) were used to
      prepare molecularly imprinted polymers exhibiting diastereoselectivity for
      cinchona alkaloids. Fluorescent spectra of the cinchona alkaloid exhibit a
      characteristic shift through binding to these polymer particles, originating most
      likely from the highly acidic residues in the imprinted polymers acting as a
      proton donator. Our results show that TFMAA based imprinted polymers can be used
      as polymer reagents for quantitating the cinchona alkaloid bound to the polymers
      without bound/free separation.

PMID- 10939403
TI  - Genetic identification by mass spectrometric analysis of single-nucleotide
      polymorphisms: ternary encoding of genotypes.
AB  - An approach to genetic identification using biallelic single-nucleotide
      polymorphism (SNP) genetic markers is described in which the three possible
      genotypes, AA, Aa, or aa, where "A" and "a" represent the two SNP alleles, are
      assigned a ternary (base 3) digit of 0, 1, or 2, respectively. Genotyping an
      individual over a panel of separate SNP markers produces a composite ternary
      genetic code that can be converted to an easily stored, decimal (base 10) genetic
      identification number. The unambiguous identification of 11 individuals is
      demonstrated using ternary genetic codes generated from MALDI-TOF mass
      spectrometric genotyping data from 7 different SNP markers.

PMID- 10939405
TI  - Investigation of enzyme kinetics using quench-flow techniques with MALDI-TOF mass
      spectrometry.
AB  - Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass
      spectrometry is combined off-line with rapid chemical quench-flow methods to
      investigate the pre-steady-state kinetics of a protein-tyrosine phosphatase
      (PTPase). PTPase kinetics are generally interrogated spectrophotometrically by
      the employment of an artificial, chromophoric substrate. However, that
      methodology places a constraint on the experiment, hampering studies of natural,
      biochemically relevant substrates that do not incorporate a chromophore. The mass
      spectrometric assay reported herein is based on the formation of a covalent
      phosphoenzyme intermediate during substrate turnover. This species is generated
      in the reaction regardless of the substrate studied and has a molecular weight 80
      Da greater than that of the native enzyme. By following the appearance of this
      intermediate in a time-resolved manner, we can successfully measure pre-steady
      state kinetics, regardless of the incorporation of a chromophore. The strengths
      of the mass-spectrometric assay are its uniform response to all substrates,
      simple and direct detection of covalent enzyme-substrate intermediates, and
      facile identification of enzyme heterogeneities that may affect enzymatic
      activity.

PMID- 10939404
TI  - Development of multichannel devices with an array of electrospray tips for high
      throughput mass spectrometry.
AB  - The basic principles of multichannel devices with an array of electrospray tips
      for high-throughput infusion electrospray ionization mass spectrometry (ESI-MS)
      have been developed. The prototype plastic devices were fabricated by casting
      from a solvent-resistant resin. The sample wells on the device were arranged in
      the format of the standard 96-microtiter well plate, with each sample well
      connected to an independent electrospray exit port via a microchannel with
      imbedded electrode. A second plastic plate with distribution microchannels was
      employed as a cover plate and pressure distributor. Nitrogen gas was used to
      pressurize individual wells for transport of sample into the electrospray exit
      port. The design of independent microchannels and electrospray exit ports allowed
      very high throughput and duty cycle, as well as elimination of any potential
      sample carryover. The device was placed on a computer-controlled translation
      stage for precise positioning of the electrospray exit ports in front of the mass
      spectrometer sampling orifice. High-throughput ESI-MS was demonstrated by
      analyzing 96 peptide samples in 480 s, corresponding to a potential throughput of
      720 samples/h. As a model application, the device was used for the MS
      determination of inhibition constants of several inhibitors of HIV-1 protease.

PMID- 10939406
TI  - Detection and quantification of neurotensin in human brain tissue by matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry.
AB  - A method was developed for mass spectrometric detection of neurotensin (NT)-like
      immunoreactivity and quantification of NT in human brain tissue. The method is
      based on immunoprecipitation followed by analysis using matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The
      identity of the major component of the immunoprecipitates as neurotensin was
      confirmed by fragment ion analysis on an electrospray ionization quadrupole time
      of-flight instrument. MALDI-TOF-MS quantification of NT was achieved using stable
      isotope-labeled NT as the internal standard, yielding an error of less than 5%.
      The method allowed detection of low-femtomole amounts of NT, staring from low
      milligram amounts of lyophilized brain tissue. In addition to NT, several other
      peptides were detected in the purified samples, most of which, according to their
      molecular masses, corresponded to fragments of NT. The method is demonstrated
      with quantification of NT from human hypothalamus tissue, and a comparison is
      made with results obtained from competitive radioimmunoassay.

PMID- 10939407
TI  - Improved calibration of time-of-flight mass spectra by simplex optimization of
      electrostatic ion calculations.
AB  - A novel time-of-flight mass calibration method has been developed. In contrast to
      conventional methods, where the relationship between ion flight time and mass is
      an arbitrary polynomial equation, this method is based on the physics of ion
      motion. Parameters needed to describe the physics are numerically optimized using
      a simplex algorithm. Once these parameters are established, unknown masses can be
      determined from their times-of-flight. This calibration method gives
      intrinsically well-behaved results, since nonlinearities (due to extraction
      delay, desorption velocity, etc.) are properly taken into account in the time-of
      flight calculation. The simplex method is compared to curve fitting for the
      analysis of time-of-flight data, and some significant advantages are
      demonstrated. Salient features of the method include greatly improved mass
      extrapolation accuracy, no loss of interpolated calibration accuracy, the ability
      to obtain an accurate calibration with a minimal number of calibrants, and the
      ability to extract unknown parameters such as desorption velocities.

PMID- 10939408
TI  - Rapid and direct sequencing of double-stranded DNA using exonuclease III and
      MALDI-TOF MS.
AB  - Application of MALDI-TOF MS to direct sequencing of dsDNA substrates is
      demonstrated using a strategy that employs exonuclease III digestion of a target
      sequence. Experimental conditions for exonuclease III have been optimized for
      this application, including addition of essential divalent metal ion cofactors. A
      short cation-exchange column was designed to provide efficient sample cleanup and
      overcome major problems arising from salt interference.

PMID- 10939409
TI  - Application of atmospheric pressure ionization time-of-flight mass spectrometry
      coupled with liquid chromatography for the characterization of in vitro drug
      metabolites.
AB  - Atmospheric pressure ionization time-of-flight mass spectrometry coupled with
      high-performance liquid chromatography was used to characterize the in vitro
      metabolites of glyburide. Metabolic products formed in vitro by human microsomes
      were separated using a C18 column with gradient elution at a flow rate of 200
      microL/min without postcolumn splitting. In-source collision-induced dissociation
      (CID) by automated nozzle potential switching was employed to obtain both
      abundant protonated molecules and characteristic fragments whose accurate masses
      were measured simultaneously by internal mass calibration, performed by
      continuous postcolumn infusion of two reference standards. The mass errors were
      within 9 ppm for all ions measured, whose abundance was greater than 5%, relative
      to the most abundant isotopic "A" ion. Exact mass differences between the parent
      drug and metabolite(s) were determined and these values corresponded to a unique
      elemental composition. The elemental compositions of all metabolite fragment ions
      were generated based upon the known compositional elements of the protonated
      molecule. The structures of metabolites and their fragment ions were proposed
      based on the determined elemental composition and in-source CID spectra. The
      elemental composition and fragmentation pathways of four cyclohexyl hydroxylation
      metabolites and one ethylhydroxy metabolite are discussed.

PMID- 10939410
TI  - Utility of accurate mass tags for proteome-wide protein identification.
AB  - An enabling capability for proteomics would be the ability to study protein
      expression on a global scale. While several different separation and analysis
      options are being investigated to advance the practice of proteomics, mass
      spectrometry (MS) is rapidly becoming the core instrumental technology used to
      characterize the large number of proteins that constitute a proteome. To be most
      effective, proteomic measurements must be high-throughput, ideally allowing
      thousands of proteins to be identified on a time scale of hours. Most strategies
      of identification by MS rely on the analysis of enzymatically produced peptides
      originating from an isolated protein followed by either peptide mapping or tandem
      MS (MS/MS) to obtain sequence information for a single peptide. In the case of
      peptide mapping, several peptide masses are needed to unambiguously identify a
      protein with the typically achieved mass measurement accuracies (MMA). The
      ability to identify proteins based on the mass of a single peptide (i.e., an
      accurate mass tag; AMT) is proposed and is largely dependent on the MMA that can
      be achieved. To determine the MMA necessary to enable the use of AMTs for
      proteome-wide protein identification, we analyzed the predicted proteins and
      their tryptic fragments from Saccharomyces cerevisiae and Caenorhabditis elegans.
      The results show that low ppm (i.e., approximately 1 ppm) level measurements have
      practical utility for analysis of small proteomes. Additionally, up to 85% of the
      peptides predicted from these organisms can function as AMTs at sub-ppm MMA
      levels attainable using Fourier transform ion cyclotron resonance MS. Additional
      information, such as sequence constraints, should enable even more complex
      proteomes to be studied at more modest mass measurement accuracies. Once AMTs are
      established, subsequent high-throughput measurements of proteomes (e.g., after
      perturbations) will be greatly facilitated.

PMID- 10939411
TI  - Protein concentration and enzyme digestion on microbeads for MALDI-TOF peptides
      mass mapping of proteins from dilute solutions.
AB  - A method for generating peptide mass maps from dilute protein samples is
      presented. The method involves the concentration of proteins from aqueous
      solution by adsorption onto reversed-phase polymeric microbeads. These beads are
      then washed extensively to remove contaminants, after which the bound proteins
      are digested with trypsin. Analysis of the digestion products is performed by
      MALDI-TOF mass spectrometry following direct deposition of the beads on a MALDI
      target, along with the matrix solution. The procedure is demonstrated using
      solutions of cytochrome c, lysozyme, and bovine serum albumin. The results of
      these digests are compared to trypsin digestions of the protein samples without
      sample preconcentration. Comparative results are also presented for protein
      solutions contaminated with 2 M NaCl, 2 M urea, or sodium dodecyl sulfate at
      concentrations up to 0.02%. These results reveal that, with the microbead
      preconcentration procedure, peptide mass maps can routinely be generated from
      highly contaminated samples with a protein concentration of only 100 nM.

PMID- 10939412
TI  - Low-speed rotary countercurrent chromatography using a convoluted multilayer
      helical tube for industrial separation
AB  - An industrial-scale countercurrent chromatographic system was developed using a
      slowly rotating helical device which can be automated and left unattended during
      the operation. It uses a multilayer coiled column consisting of long convoluted
      Teflon tubing of 0.85 cm i.d., which provides sufficient retention of the
      stationary phase under a relatively high flow rate. The column is mounted on a
      seal-less continuous-flow rotary device which eliminates various complications
      such as leakage and clogging as often caused by the use of a conventional rotary
      seal. Using a multilayer coiled column with a 10-L capacity, 150 g of crude tea
      extract was successfully purified, yielding 40 g of epigallocatechin gallate of
      over 92.7% purity at a recovery rate of 82.6%. The present system can be scaled
      up for a kilogram-scale separation.

PMID- 10939413
TI  - Assessing the molecular weight of a conducting polymer by grazing emission XRF
AB  - A spray coated thin film of all-E-poly[(3-methoxy-2,5-thiophenediyl- 1',2'
      ethenediyl)(4"-methoxy-2",5"-thiophenediyl- 1",2"-ethenediyl)], a conducting
      polymer, was analyzed by grazing emission X-ray fluorescence spectrometry.
      Measuring the S/CI ratio in this sulfur-containing polymer with one terminal
      chlorine allowed us to determine the chain length and, hence, the molecular
      weight. The result was in acceptable agreement with that of a well-established
      method for the determination of the molecular weight of polymeric materials.

PMID- 10939414
TI  - A binderless, bulk-modified, renewable surface amperometric sensor for NADH and
      ethanol.
AB  - Graphite particles are exfoliated and subsequently functionalized with toluidine
      blue. The resulting covalently modified graphite particles are restacked without
      any binder to form a surface-renewable, bulk-modified electrode. Electrocatalytic
      oxidation of NADH and its application in the amperometric biosensing of ethanol
      using alcohol dehydrogenase enzyme have been demonstrated with this material.

PMID- 10939415
TI  - A method to define the carboxyl terminal of proteins.
AB  - Accurate definition of the carboxyl terminal of proteins is necessary for
      elucidating posttranslational processing at the C-terminal and more generally for
      characterizing protein primary structures. Here, we describe a strategy for
      isolating and characterizing the C-terminal peptide of a protein after
      proteolysis with endoprotease Lys-C. Isolation is achieved using anhydrotrypsin,
      a catalytically inert derivative of trypsin that binds peptides containing lysine
      or arginine residues at their C-termini without cleaving them. Rapid, accurate
      characterization of the isolated C-terminal peptide is achieved by mass
      spectrometry. Initial identification of the C-terminal peptide is obtained by
      comparing matrix-assisted laser desorption/ionization time-of-flight mass spectra
      of the digest prior to and after incubation with anhydrotrypsin. Characterization
      of the C-terminal sequence is achieved by capillary-HPLC electrospray ionization
      tandem mass spectrometry of the isolated peptide using a quadrupole ion trap mass
      spectrometer in the selective reaction monitoring mode. This strategy was
      successfully applied to the characterization of the C-terminal of proteins with
      molecular masses ranging up to 56 kDa.

PMID- 10939416
TI  - Photocatalytic sensor for chemical oxygen demand determination based on oxygen
      electrode.
AB  - The construction and performance evaluation of a novel Chemical Oxygen Demand
      (COD) sensor is described. The sensor measures, using an oxygen electrode, a
      decrease of dissolved oxygen of a given sample resulting from photocatalytic
      oxidation of the organic compounds therein. As the photocatalyst, titanium
      dioxide (TiO2) fine particles adsorbed on a translucent poly(tetrafluoroethylene)
      (PTFE) membrane was used. The oxygen electrode with the membrane attached on its
      tip was used as the sensor probe. The operation characteristics of the sensor are
      demonstrated using an artificial wastewater and real water samples from lakes in
      Japan. This method is considered to be reliable, in that the observed parameter
      is close to the theoretical definition of chemical oxygen demand (COD), the
      amount of oxygen consumed for oxidation of organic compounds.

PMID- 10939417
TI  - Combinatorial screening of enzyme activity by using multiplexed capillary
      electrophoresis.
AB  - Efficient and comprehensive screening of enzyme activity was accomplished in a
      combinatorial array of 96 reaction microvials. Quantitation of the extent of the
      reaction at well-defined time intervals was achieved by using 96-capillary array
      electrophoresis coupled with a multiplexed absorption detector. Capillary
      electrophoresis provides high separation resolution to isolate the product from
      the reactants. Absorption detection provides universal applicability to
      combinatorial screening. For the conversion of NADH to NAD+, the catalytic
      activity of LDH was confirmed to be the highest at pH 7. This scheme should be
      useful for high-throughput drug discovery, clinical diagnosis, substrate binding,
      as well as combinatorial synthesis.

PMID- 10939419
TI  - Determination of water in NIST reference material for mineral oils
AB  - The accuracy of the reference concentrations of moisture in electrical insulating
      oil RM 8506 and lubricating oil RM 8507 (both of mineral type) and specified by
      the National Institute of Standards and Technology (NIST) as containing 39.7 and
      76.8 ppm (w/w) water, respectively, has recently been the subject of debate in
      this journal. To shed some further light on this controversy, we report in this
      correspondence results for these oils obtained by two additional methods, one
      based on specially designed reagents for diaphragm-free Karl Fischer (KF)
      coulometry and the other based on the concept of stripping at elevated
      temperature/continuous KF coulometry. A positive interference effect was shown to
      take place for RM 8506 when the direct coulometric method was used. If the
      results are corrected for this, the values including six different procedures
      varied in the range 13.5-15.6 ppm (w/w). For RM 8507, all values were between
      42.5 and 47.2 ppm (w/w), which means that the values recommended by NIST for both
      reference oils using volumetric titration are about twice as high as those
      obtained with the other techniques. A possible explanation for this discrepancy
      is presented.

PMID- 10939418
TI  - Eight hundred-base sequencing in a microfabricated electrophoretic device.
AB  - The human genome will be sequenced using capillary array electrophoresis
      technology. Although currently achieving only 550 base reads per run, capillary
      arrays have increased the efficiency and lowered the cost of sequencing by
      eliminating gel plate preparation, reducing sample volumes, and offering
      automation and speed. However, much higher throughput and greater cost reductions
      are needed. The next major advancement in sequencing technology is expected from
      the development of arrays of microfabricated channels in a plate or "chip"
      format. For de novo sequencing, the practical utility of the microdevice approach
      has been limited by device length to a read of 500-600 bases per run. We
      demonstrate a significant milestone for a microfabricated device by obtaining an
      average read length of 800 bases in 80 min (98% accuracy) for either M13
      standards or DNA sequencing samples from the Whitehead Institute Center for
      Genomic Research (WICGR) production line. This result is achieved in 40-cm-long
      channels using a new class of large-scale microfabricated devices. Both
      microfabrication of extended structures and achievement of long reads are
      essential steps toward a 384-lane very-large-scale microfluidic (VLSMF) system
      for ultrahigh-throughput DNA sequencing analysis, currently under construction in
      our laboratory.

PMID- 10939420
TI  - Comments on "An extraction method for determination of ginkgolides and bilobalide
      in Ginkgo leaf extracts.

PMID- 10939421
TI  - Panic in a general practice population: prevalence, psychiatric comorbidity and
      associated disability.
AB  - BACKGROUND: Panic disorder and simple panic are known to be common disorders
      associated with various physical and psychological difficulties, but their
      prevalence rates as reported in the literature vary widely. This paper is the
      result of a survey of panic in a general practice population, and discusses
      prevalence rates, screening for panic and psychiatric comorbidity. Comparisons
      are made between subjects with and without panic with regard to their self
      reported disability. METHODS: A random sample of 2000 individuals from the
      patient list of a group general practice were sent a questionnaire screening for
      panic attacks and asking for levels of everyday functioning and disability.
      Patients who screened positive for panic were interviewed using the Structured
      Clinical Interview for DSM III R. RESULTS: A total of 1152 people responded to
      the questionnaire. In this sample, the lifetime prevalence of panic was 8.6%, and
      well over half of these had single or multiple additional psychiatric diagnoses.
      People with panic were found to perceive themselves as significantly less
      physically and psychologically healthy. It was found that screening questions
      that focussed on the psychological symptoms of panic missed a significant
      proportion of subjects with panic, particularly men. CONCLUSION: The level of
      psychiatric comorbidity in this study mirrors that found by other investigators.
      The amount of perceived disability suffered by individuals with panic is
      considerable. This study may contribute to the argument that people with panic
      should be identified at an early stage, to prevent unnecessary investigation and
      ensure adequate treatment.

PMID- 10939422
TI  - Continuity of care and clinical outcome: a prospective cohort study.
AB  - BACKGROUND: Continuity of care is a central objective of community psychiatric
      services, but there is no consensus about its measurement. AIMS: We developed
      measures of continuity of care suitable for routine use, and measured continuity
      and individual patient outcome over a period in which community services were
      developing. METHOD: One hundred patients with severe mental illness receiving
      continuing care from two sectorised services were sampled and interviewed. Data
      were collected concerning their care over 20 months prior to interview. After 20
      months prospective follow-up, they were re-interviewed. Continuity was defined
      as: perceived accessibility of services and knowledge about them, the number of
      keyworkers in a defined period of time, and the proportion of time out of contact
      with services. RESULTS: Continuity of care improved significantly on all measures
      over the period of the study. Individual patient outcome also improved, but in
      multiple regression models including clinical and demographic variables, measures
      of continuity were not significant predictors of outcome. Continuity was similar
      for white and non-white patients. CONCLUSION: Simple measures of continuity are
      useful in evaluating changes in the process of care, but they are not
      straightforwardly related to individual outcome.

PMID- 10939423
TI  - Cross-cultural validity of the Amritsar Depression Inventory and the General
      Health Questionnaire amongst English and Punjabi primary care attenders.
AB  - BACKGROUND: In order to estimate the health needs of cultural groups, the cross
      cultural validity of instruments requires investigation in distinct cultural
      rather than ethnic or racial groups. METHOD: We screened 'Punjabi' and 'English'
      primary care attenders in South London (UK), using the General Health
      Questionnaire (GHQ-12), an English origin instrument, and the Amritsar Depression
      Inventory (ADI), which was developed in the Punjab in India. The criterion
      measure was the Clinical Interview Schedule (CIS-R). We calculated the validity
      coefficients, optimal thresholds and the area under the 'Receive Operating
      Characteristic' curve to compare cross-cultural performance. We identified items
      on each questionnaire that contribute to performance of the instruments. RESULTS:
      The GHQ-12 has high validity coefficients in both cultural groups. The ADI
      performs as well amongst English subjects, but among Punjabis it is poorer than
      the GHQ-12. Among Punjabis who have been resident in the UK for over 30 years,
      the ADI performs no better than chance. Few items on the ADI or the GHQ are
      strongly predictive of case status. CONCLUSIONS: The GHQ-12 shows good validity
      in both cultures. Expressions of distress may change due to acculturation.
      'Culturally sensitive' screening instruments need to reflect this. Further work
      might attend to the changing expressions of distress following migration.

PMID- 10939424
TI  - Political change and course of schizophrenia in East Germany, 1984-1994.
AB  - BACKGROUND: We tested the hypothesis that the political change occurring in East
      Germany after the fall of the Berlin Wall in November 1989 affected patients with
      long-term schizophrenia, resulting in more and longer hospitalisations. METHODS:
      In two samples in East Germany (120 patients in East Berlin, 70 patients in
      Chemnitz) and in a control group from West Berlin (40 patients), hospitalisations
      for each month between November 1984 and October 1994 were assessed. Each sample
      included all schizophrenia patients who were in continuous treatment in the given
      community mental health centre throughout the full observation period. RESULTS:
      Hospitalisation indices were not higher after November 1989 than before in any of
      the groups. CONCLUSIONS: There is no evidence that political change in East
      Germany negatively affected the course of longterm schizophrenia as assessed by
      hospitalisations. If consistent medical care is provided, characteristics of the
      political system may have less impact on the course of schizophrenia than is
      sometimes assumed.

PMID- 10939425
TI  - Predictors for Depression, Anxiety and psychotic symptoms in a very elderly
      population: data from a 3-year follow-up study.
AB  - BACKGROUND: This study examined the predictors for Depression, Anxiety and
      psychotic symptoms in a population of very elderly persons. METHODS: A total of
      894 persons with a mean age of 84.5 years were examined twice using a 3-year
      interval. Physicians performed a structured psychiatric interview and persons
      with a current disorder or symptom were excluded. RESULTS: Persons who had a
      history of psychosis, were affected with Dementia and had an insufficient social
      network had an increased frequency of psychotic symptoms. A history of
      Depression/Anxiety increased the frequency of having Anxiety and Depression. An
      insufficient social network was associated with Anxiety. CONCLUSIONS: In this
      study Anxiety, Depression and psychotic symptoms in the very elderly seem to be
      linked to a lifetime psychological vulnerability, since all were related to a
      previous psychiatric history. Additionally, psychotic symptoms seemed to emerge
      due to structural brain damage, as seen in Dementia.

PMID- 10939426
TI  - Lifetime stressors and recurrent depression: preliminary findings of the Adult
      Life Phase Interview (ALPHI).
AB  - BACKGROUND: The well-established association between stress and depression is
      explored in a lifespan context in relation to adverse childhood experience. A new
      retrospective interview instrument, the Adult Life Phase Interview (ALPHI)
      examined the number of chronic stressors (or 'adversities') experienced over the
      adult life course in relation to chronic or recurrent clinical depression. The
      role of such lifetime adversity in mediating the relationship between childhood
      neglect/ abuse and adult disorder was examined. METHOD: The ALPHI uses an
      investigator-based, contextual approach suited to retrospective and time-linked
      enquiries. Reliability of the instrument was found to be satisfactory. Its
      association with both lifetime clinical depression and childhood neglect or abuse
      was examined in a community series of 198 women, consisting of 99 sister pairs,
      where one-half of the series was selected for having had adverse childhood
      experience and the other for comparison. RESULTS: Adult adversity, both at
      settled/fixed times and at times of major life change, was significantly higher
      among those with prior childhood neglect or abuse. Both a high adult adversity
      score and childhood neglect or abuse were related to chronic or recurrent
      episodes of clinical depression, with logistic regression indicating both indices
      contributed independently to disorder. The same results held when controls were
      made for sister status, given possible familial bias in experience, and for age,
      since women under age 25 had fewer adult phases and less adversity. CONCLUSIONS:
      Characteristics of adult life phases and change-points are described and the
      relevance of the measure for intensive survey work seeking to investigate
      relationships between lifespan experience and depression is discussed.

PMID- 10939427
TI  - Somatisation in primary care: clinical judgement and standardised measurement
      compared.
AB  - BACKGROUND: In daily practice general practitioners (GPs) generally rely on their
      clinical judgement in assessing whether patients somatise distress. Nevertheless,
      conclusions derived from research on somatisation in primary care are largely
      based on standardised measurements of somatisation. We investigated the relation
      between GPs' clinical judgement of somatisation and a somatisation research
      instrument (DSM-III-R), and examined how both operationalisations of somatisation
      related to other important variables. METHODS: In nine general practices, 407
      frequently attending patients answered a questionnaire on somatisation symptoms,
      while the GPs gave their judgement on somatisation and communication for each
      patient. Other variables were extracted from the registered health status of the
      patients. RESULTS: We found a weak association (correlation: 0.27) between the
      GPs' judgement and the research instrument; however, relations with other
      variables showed that both operationalisations were very similar constructs. The
      research instrument incorporated more psychological problems (depression and
      anxiety), while the GPs' judgement of somatisation was more influenced by
      attendance rate and by aspects of communication with the patient. CONCLUSION: For
      research addressing somatisation in primary care as a practical clinical problem,
      the operationalisation of somatisation should include the clinical judgement of
      the practitioner as well, thereby widening the focus from co-morbid mental
      disturbances to communication aspects.

PMID- 10939428
TI  - Survival results of neoadjuvant chemotherapy for advanced squamous cell carcinoma
      of the head and neck.
AB  - BACKGROUND: We carried out an open, randomized multi-center clinical trial for
      advanced head and neck cancer between April 1991 and December 1992. In this
      report, we update the results and analyze the 5-year survival results. METHODS:
      Thirty-two patients with previously untreated stage III and IV resectable
      squamous cell carcinoma of the oral cavity and pharynx were entered into the
      study. The PEM regimen consisted of cisplatin 60 mg/m2 2 h infusion on day 1,
      etoposide 40 mg/m2 1 h infusion on days 1, 2 and 3 and mitomycin-C 7 mg/m2 i.v.
      bolus on day 1. RESULTS: Among the 32 patients entered into this trial, eight
      were disqualified from the analysis. Of the remaining 24 patients, 13 were given
      neoadjuvant chemotherapy (NAC) and 11 underwent surgery alone. Among the 13
      patients who received NAC, four achieved a complete response (31%) and three a
      partial response (23%), with an overall response rate of 54%. Myelosuppression
      was a major side effect. Thrombocytopenia and anemia were dose-limiting
      toxicities. Other adverse reactions, including mucositis, were all mild and
      transient. The overall 5-year survival after NAC and without NAC were 83 and 62%,
      respectively. The survival difference was not statistically significant (p =
      0.33). CONCLUSIONS: NAC does not appear to play a role in the treatment of cancer
      of the oral cavity and pharynx with our PEM regimen. However, the degree of
      toxicity was limited in our trial and therefore attempts to increase the dosage
      and/or revise the administration schedule for cancer of the pharynx and T1 to T3
      tumor disease appear warranted.

PMID- 10939429
TI  - Computed tomographic fluoroscopy-guided transthoracic needle biopsy for diagnosis
      of pulmonary nodules.
AB  - BACKGROUND: The purpose of this study was to evaluate the usefulness of computed
      tomographic (CT) fluoroscopy-guided transthoracic needle biopsy (TTNB) with an 18
      gauge automatic biopsy gun for the diagnosis of pulmonary nodules. METHODS:
      Between March 1996 and January 1998, 50 patients in whom pulmonary lesions could
      not be diagnosed cytopathologically with fiberoptic bronchoscopy or were not
      clearly visualized with fluoroscopy underwent CT fluoroscopy-guided TTNB.
      RESULTS: Final pathological diagnoses were 23 lung carcinomas, five pulmonary
      metastases and 22 benign lesions. Sufficient tissue for analysis was obtained
      from 48 of the 50 lesions (96%). The overall diagnostic yield of CT fluoroscopy
      guided TTNB was 90%. The sensitivity, specificity and accuracy for malignancy
      were 89%, 100% and 94%, respectively. In 20 of the 22 cases (91%) of benign
      lesions, histological analysis yielded correct and specific diagnoses.
      Complications occurred in 22 of the 50 cases (44%). The most common complication
      was pneumothorax, which occurred in 21 of the 50 cases (42%). Chest tube
      insertion was required in 6 (12%). CONCLUSIONS: Although CT fluoroscopy could not
      decrease the complication rate, CT fluoroscopy-guided TTNB with an automatic
      biopsy gun appears to be a promising technique for diagnosing pulmonary lesions,
      particularly benign lesions.

PMID- 10939430
TI  - Blue nodes left behind after vital blue dye-guided axillary sentinel node biopsy
      in breast cancer patients.
AB  - BACKGROUND: Vital dye-guided sentinel node biopsy is affordable in most
      hospitals, but may be of limited accuracy in identifying all sentinel nodes.
      Leaving sentinel nodes in the axilla may result in a false nodal staging of
      breast carcinomas. METHODS: From a series of 112 successful sentinel lymph node
      biopsies with Patent Blue dye followed by axillary dissection, 10 cases were
      identified where 1-3 blue nodes were found in the axillary dissection specimens.
      These 10 cases were compared with those which had all blue nodes identified
      during surgery. Five of the 10 patients with missed blue nodes also underwent
      lymphoscintigraphy with 99m-Tc-labeled colloidal human albumin and all of their
      nodes were subjected to external gamma well counting postoperatively. RESULTS:
      There were six false-negative sentinel lymph node biopsies overall, but none in
      patients with missed blue nodes. Patients with primarily unidentified blue nodes
      had more sentinel nodes and a higher rate of multiple sentinel nodes than the
      others. CONCLUSION: Blue nodes missed during surgery may be either true sentinel
      nodes or second echelon nodes labeled by dye overflow. This type of error may
      occur in <8% of patients and may lead to false-negative sentinel node-based
      staging in an even smaller proportion of cases (none in this series).

PMID- 10939432
TI  - Expression of bone morphogenetic protein and its receptors in osteosarcoma and
      malignant fibrous histiocytoma.
AB  - BACKGROUND: Bone morphogenetic protein (BMP) activity has been found in cases of
      malignant fibrous histiocytoma (MFH) and osteosarcoma but only tumors in the
      latter category show evidence of ossification. The aim of this study was to try
      to understand this difference by examination of the distribution of BMP and its
      receptors (BMPR) for this bone inducing protein in these tumors. METHODS:
      Sections of 11 osteosarcoma and 10 MFH were analyzed immunohistochemically for
      BMP and BMPRs by use of the avidin-biotin peroxidase method. RESULTS: Nine out of
      11 osteosarcoma cases (80.1%) showed positive staining for both BMP and BMPRs.
      Two cases of chondroblastic type osteosarcoma did not show any significant
      staining for BMP and BMPRs. In eight out of 10 MFH cases (80%) there was positive
      staining for BMP. No immunoreactivity for BMPRs was found in any case of MFH.
      CONCLUSIONS: MFH does not express BMPRs and this may be the reason why-MFH tumors
      do not ossify, even in the presence of BMP.

PMID- 10939431
TI  - Six-year disease-free survival of a patient with metastatic eyelid squamous cell
      carcinoma and colon adenocarcinoma after repeated postoperative adoptive
      immunotherapy.
AB  - A 74-year-old male was affected concurrently with squamous cell carcinoma of the
      left eyelid and adenocarcinoma of the colon, both with lymph node metastasis. He
      underwent exenteration of the left orbit with left modified radical neck
      dissection and subsequently resection of the transverse colon with regional lymph
      node dissection. The patient has been treated by an adoptive immunotherapy as a
      sole postoperative modality without receiving any chemotherapeutic agents causing
      immunosuppression. For the adoptive immunotherapy, autologous peripheral blood
      lymphocytes were activated with an immobilized anti-CD3 antibody and IL-2 for 14
      days (the CD3-AT cells). The infusion with 1.38 x 10(10) CD3-AT cells has been
      repeated 150 times in total at the time of writing. Neither recurrence nor
      additional metastasis has been detected for 6 years after surgery.

PMID- 10939433
TI  - Venous gangrene in a patient with adenocarcinoma of the lung.
AB  - Cancer-related thromboembolism is a severe but not uncommon paraneoplastic
      syndrome in mucinous cancer patients. However, cancer-induced venous gangrene is
      extremely rare and has never been reported in the English literature. Here, we
      present a case of lung cancer complicated with venous gangrene of the left foot.
      An elevated serum anticardiolipin level was detected during hospitalization, but
      the patient's clinical condition stabilized after heparinization. We suggest that
      in cancer patients, an elevated serum anticardiolipin antibody level might be a
      warning sign of an impending thrombotic event and that low-molecular-weight
      heparin is a sensible choice in treating this kind of cancer-related
      thromboembolism.

PMID- 10939434
TI  - Primary squamous cell carcinoma of the breast during lactation: a case report.
AB  - A case of primary squamous cell carcinoma of the breast during lactation is
      reported. The patient was a 32-year-old woman, in post-partum lactating 18 months
      after delivery, who was referred to our hospital following detection of a lump in
      her left breast during physical examination in mass screening for breast cancer.
      The tumor, palpated in the upper outer quadrant of the left breast, was firm,
      well-defined and 2.8 x 2.6 cm in size. Ultrasonograms identified an irregular
      shaped hypoechoic lesion and mammograms revealed a well-defined, circumscribed
      tumor. Based on these findings, breast cancer was suspected and an excisional
      biopsy was performed. The resected specimen was a firm, solid and circumscribed
      tumor with central hemorrhage. Microscopic findings demonstrated that the tumor
      consisted of an invasive ductal carcinoma with marked squamous metaplasia, such
      as keratinization and squamo-columnar junction. Breast-conserving surgery was
      performed and no lymph node involvement was noted. Both estrogen and progesterone
      receptors of the tumor were negative. Generally, the size of both squamous cell
      carcinoma and carcinoma during the lactation period tends to be larger than
      ordinary carcinomas. In this case, the cancerous lesion was detected at a
      relatively early stage. Although the cancerous lesion was detected at a
      relatively early stage and no lymph node involvement was noted, lung metastases
      occurred within 12 months of the surgery. Malignant potential is generally
      considered to be high in cases of squamous cell carcinoma of the breast with
      lactation and thus intensive treatment potentially resulting in severe side
      effects was considered to be necessary for this patient.

PMID- 10939435
TI  - Epidemiology in Japan: the emergence of observational cancer research.

PMID- 10939436
TI  - Lung cancer mortality rates by prefectures in Japan.

PMID- 10939437
TI  - Simulation of electrophoretic separations: effect of numerical and molecular
      diffusion on pH calculations in poorly buffered systems.
AB  - A poorly buffered cationic isotachophoresis separation, first simulated by
      Reijenga and Kasica, has been revisited to demonstrate that an inconsistent
      description of solute and charge transport can lead to significant errors in the
      pH calculation. The separation is first simulated using a second-order finite
      difference scheme to show that omission of molecular diffusion from the charge
      balance results in a pH profile with spurious dips in the steady-state zone
      boundaries. The separation is also simulated using two first-order methods that
      employ numerical diffusion to stabilize solutions against spatiotemporal
      oscillations. Similar pH dips are generated by these first-order schemes, even
      when molecular diffusion is included in the charge balance, if numerical
      diffusion is not considered amongst the charge transport mechanisms. When
      numerical diffusion, inherent in the discretization of the component balances, is
      introduced to the charge balance, the spurious pH dips are eliminated. The
      results indicate that (i) pH dips originally reported by Reijenga and Kasicka are
      merely artifacts of their numerical model, and (ii) nonoscillatory numerical
      techniques, such as upwinding and flux limiters, should incorporate artificial
      transport mechanisms in the charge as well as the solute balances.

PMID- 10939438
TI  - Structural characterization of oligosaccharides in recombinant soluble human
      interferon receptor 2 using fluorophore-assisted carbohydrate electrophoresis.
AB  - The N-linked oligosaccharide profiles (banding patterns in gels) and structures
      of recombinant soluble human interferon receptor 2 (r-shIFNAR2) were determined
      using fluorophore-assisted carbohydrate electrophoresis (FACE, Glyko, Novato,
      CA). The method involves releasing N-linked oligosaccharide moieties from a
      glycoprotein by digestion with peptide-N glycanase (PNGase F), labeling the
      released oligosaccharides with the fluorescent dye 8-aminonaphthalene-1,3,6
      trisulfonate (ANTS), and separating the labeled oligosaccharides by gel
      electrophoresis. The isolated oligosaccharides in the bands from the profiling
      gels can then be sequenced using exoglycosidases to reveal the oligosaccharide
      structures. The oligosaccharide profile of r-shIFNAR2 consists of at least nine
      oligosaccharide bands. The relative amount of oligosaccharide in each band can
      vary, depending on the culture conditions of the source cells. FACE structural
      analysis shows that r-shIFNAR2 contains only core-fucosylated N-linked
      oligosaccharides, most of which are fully sialylated (approximately 92%). The
      major types and relative amounts of the oligosaccharides from a representative
      sample are: disialylated, galactosylated, biantennary (15%); trisialylated,
      galactosylated, triantennary (19%), tetrasialylated, galactosylated,
      tetraantennary (30%), and N-acetyllactosamine-containing higher-order
      oligosaccharides including tri-, tetra-, and pentaantennary (28%). The remaining
      oligosaccharides are not fully sialylated and/or not fully galactosylated di-,
      tri-, and tetraantennary structures (approximately 5%) and unidentified
      structures (approximately 3%). A method for determining the types and structures
      of the N-acetyllactosamine containing oligosaccharides is also reported in this
      study.

PMID- 10939439
TI  - Difference in electrophoretic mobility and plasmic digestion profile between four
      recombinant fibrinogens, gamma 308K, gamma 308I, gamma 308A, and wild type (gamma
      308N).
AB  - We have produced recombinant gamma-chain variant fibrinogens, gamma308K,
      gamma308I, and gamma308A simultaneously with wild-type fibrinogen, gamma-308N, by
      genetic protein engineering using Chinese hamster ovary cells. Although all three
      variant fibrinogens are a result of a single amino acid substitution, the
      aberrant gamma-chains of gamma308K and gamma308I fibrinogens migrated faster than
      gamma308N. Furthermore, plasmic digestion profiles were examined in the presence
      of 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
      (EGTA) or 1 mM CaCl2. In the presence of EGTA, the three variant fibrinogens were
      digested into D1 and D2 fragments slightly faster than wild type. In addition,
      the D2 fragment derived from gamma308K was further digested into D3 by plasmin
      much faster than that from gamma308N. These data suggest that cleavage of
      gamma356Lys-gamma357Ala bond by plasmin in gamma308K, gamma308I, and gamma308A is
      slightly accelerated and the gamma302Lys-gamma303Phe bond is cleaved by plasmin
      rapidly in only the gamma308K variant. Furthermore, the substitution of Lys for
      gamma308Asn results in the generation of a new plasmin cleavage site between
      gamma308Lys and gamma309Gly in the presence of EGTA. In conclusion, a
      substitution at residue gamma308Asn may cause a conformational change in the
      gammachain of fragment D affecting polymerization and plasmin cleavage.

PMID- 10939441
TI  - Metric representation of DNA sequences.
AB  - A metric representation of DNA sequences is borrowed from symbolic dynamics. In
      view of this method, the pattern seen in the chaos game representation of DNA
      sequences is explained as the suppression of certain nucleotide strings in the
      DNA sequences. Frequencies of short nucleotide strings and suppression of the
      shortest ones in the DNA sequences can be determined by using the metric
      representation.

PMID- 10939440
TI  - Crystallization of chicken liver (basic) fatty acid binding protein after
      purification in multicompartment electrolyzers with isoelectric membranes.
AB  - A preparation of chicken liver (basic) fatty acid binding protein was purified to
      homogeneity in multicompartment electrolyzers with isoelectric membranes. Large
      amounts of the isoelectric point (pI) 9.7 protein were collected into a
      compartment delimited by pI 8.8 and 11.0 membranes. The protein thus purified
      produced crystals which diffract to higher resolution than those obtained by
      purification via preparative isoelectric focusing (IEF) in soluble carrier
      ampholytes. In addition, a novel orthorhombic form with a different molecular
      packing was obtained. It is hypothesized that, when using conventional IEF,
      traces of carrier ampholytes could adhere to the protein, particularly in the
      hydrophobic ligand-binding pocket, rendering the interpretation of the electron
      density maps difficult. Multicompartment electrolyzers do not present this
      drawback, since they are based on insoluble buffering species.

PMID- 10939442
TI  - Conformational isomers of curved DNA molecules can be observed by polyacrylamide
      gel electrophoresis.
AB  - Dimers, trimers and higher multimers of two 147-base pair restriction fragments
      called 12 A and 12B, obtained from the MspI digest of plasmid pBR322, migrate as
      sharp bands in agarose and dilute polyacrylamide gels, indicating that they are
      homogeneous in molecular weight. However, the electrophoretic bands corresponding
      to multimers of the curved fragment 12A are split into sharp sub-bands in more
      concentrated polyacrylamide gels. The relative intensities and spacing of the sub
      bands depend on the number of monomers in the multimer, the pH of the buffer, and
      the presence or absence of divalent cations in the solution. Since band splitting
      is not observed for the normal 12B multimers under any gel-running conditions,
      the sub-bands observed for multimers of the curved fragment 12A must be
      attributed to conformational isomers which are in slow exchange on the
      electrophoretic time scale. Band splitting is also observed for multimers of a
      curved DNA fragment containing the kinetoplast bending locus and for plasmid
      pUC19 linearized by digestion with certain restriction enzymes. Plasmid pUC19
      contains two nearly equidistant regions of intrinsic curvature (Strutz, K.,
      Stellwagen, N. C., Electrophoresis 1996, 17, 989-995). Hence, DNA molecules
      containing two or more regions of curvature exist as discrete subpopulations of
      conformational isomers which can be observed as separate bands migrating in
      polyacrylamide gels.

PMID- 10939443
TI  - A rapid fluorescence based multiplex polymerase chain reaction--single-strand
      conformation polymorphism method for p53 mutation detection.
AB  - We have developed a fast single-strand conformation polymorphism (SSCP) technique
      to screen for mutations and polymorphisms in exons 5-8 of the human tumor
      suppressor gene p53. We use multiplex polymerase chain reaction (PCR) to amplify
      the four exons in one single PCR reaction and then fluorescent SSCP for
      screening. p53 fragments are labeled with three different colors and a fourth
      color is used for an internal size marker calibrating the gel. The method was
      evaluated in two ways: (i) 16 different cell lines with known mutations were
      tested blindly for band-shifts with SSCP, and (ii) 32 human urinary bladder
      cancer samples were screened for mutations using the present technique. After
      screening for mutations all exons from all samples were sequenced, both sense as
      well as antisense strands. Evaluating the method with four different gels shows
      that 21/23 mutations and polymorphism were detected in the cell lines and that
      10/10 mutations and polymorphisms were detected in the patient samples.
      Sensitivity, specificity, positive and negative predictive values were 91/100%,
      88/ 97%. 78/77% and 96/100% for cell lines / patient samples, respectively.
      Sensitivity, using one SSCP gel only, was 87% (20/23) for cell lines and 90%
      (9/10) for patient samples. We conclude that our modified SSCP technique is
      efficient and has a sensitivity close to 100% in detecting mutations.

PMID- 10939444
TI  - Evaluation of new adsorbed coatings in chiral capillary electrophoresis and the
      partial filling technique.
AB  - When using chiral selectors and the partial filling technique in capillary
      electrophoresis, a suitable and reproducible suppression of the electroosmotic
      flow is still a challenging issue, and there are a number of reasons to find
      alternatives to the use of covalently coated capillaries for such a particular
      application. In this paper, new achiral, neutral, and water-soluble polymers are
      evaluated as adsorbed polymers for the suppression of electroosmotic flow (EOF)
      when employing chiral capillary electrophoresis and the partial filling
      technique. Four chiral selectors, namely a cationic cyclopeptide, vancomycin,
      human serum albumin and riboflavin binding protein have been chosen for this
      study and some analytes such as derivatized amino acids, promethazine and
      prilocaine have been used as test compounds. Reproducibility of migration times,
      resolution, and selectivity as well as efficiency are reported to critically
      evaluate the performance of the adsorbed coatings. Results are compared to
      parallel data obtained with fused-silica and polyvinyl alcohol-coated
      capillaries.

PMID- 10939445
TI  - High speed single nucleotide polymorphism typing of a hereditary haemochromatosis
      mutation with capillary array electrophoresis microplates.
AB  - A single nucleotide polymorphism (SNP) typing assay is developed and evaluated on
      a microfabricated capillary array electrophoresis system. Using fluorescently
      labeled allele-specific primers, the S65C (193A-->T) substitution associated with
      hereditary haemochromatosis in the HFE gene is genotyped. The covalently labeled
      polymerase chain reaction (PCR) products are separated on a microfabricated
      radial capillary array electrophoresis microplate using nondenaturing gel media
      in under two minutes. Detection is accomplished with a laser-excited rotary
      confocal scanner. The Rox-labeled A-allele specific amplicon (211 bp) is
      differentiated from the R110-labeled T-allele specific amplicon (201 bp) by both
      size and color. This study demonstrates the feasibility of using allele-specific
      PCR with covalently labeled primers for high speed fluorescent SNP typing on
      microfabricated radial capillary array electrophoresis microplates.

PMID- 10939446
TI  - Capillary electrophoresis of histone H1 variants at neutral pH in dynamically
      modified fused- silica tubing.
AB  - Existing methods for the analysis of histone H1 by capillary electrophoresis (CE)
      employ acidic buffers (pH <3.0) to suppress silanol ionization and minimize the
      loss of these extremely basic proteins by adsorption to capillary walls. Here we
      describe the use of Polybrene (PB) as a dynamic modification reagent in a simple
      procedure that facilitates the analysis of chicken H1 at neutral pH. PB is
      adsorbed to the inner surfaces of capillaries to render them cationic prior to
      use and a low concentration of PB is included in the electrolyte to replenish the
      coating during use. Inclusion of ethylenediaminetetraacetic acid (EDTA) in the
      electrolyte results in the assembly of a dynamic cation-exchange layer upon the
      immobilized PB that influences the relative mobilities of H1 variants. The six
      nonallelic variants of H1 known in this species as well as certain allelic
      variants are resolved. Because the procedure is effective in preventing the
      adsorption of proteins as basic as H1 at neutral pH, this strategy should
      facilitate CE analyses of many basic proteins under conditions that maintain
      their native conformation.

PMID- 10939447
TI  - Characterization of human alcohol dehydrogenase isoenzymes by capillary
      isoelectric focusing-mass spectrometry.
AB  - The human liver alcohol dehydrogenase (ADH) isoenzymes are currently believed to
      play a major role in ethanol metabolism, accounting for most of the ethanol
      oxidized in the liver. They have similar molecular masses and similar isoelectric
      point (pI) values (the 13 possible isoenzymes having pIs in the range of 8.26
      8.87), making their characterization a significant analytical challenge.
      Capillary isoelectric focusing (CIEF) coupled on-line with electrospray
      ionization - Fourier transform ion cyclotron resonance (ESI-FTICR) mass
      spectrometry was applied to separate and characterize mixtures of alphaalpha,
      beta1beta1 and beta3beta3 ADH isoenzymes. Seven different species were resolved
      by the separation in the pI 8.26-8.67 range. ESI-FTICR analysis of native ADHs
      revealed that each noncovalent ADH complex contains two monomeric protein units
      and four zinc atoms. The combination of CIEF separations with mass spectrometry
      appears well-suited for detailed characterization of ADH isozymes, and the
      attomole level sensitivity of FTICR should allow very small samples to be
      addressed.

PMID- 10939448
TI  - Direct capillary electrophoretic detection of carbohydrate-deficient transferrin
      in neat serum.
AB  - Transferrin, an iron transport protein found in serum and cerebrospinal fluid, is
      known to be microheterogeneous with respect to its carbohydrate and sialic acid
      content. The forms of transferrin deficient in sialic acid and/or carbohydrate,
      termed carbohydrate-deficient transferrin (CDT), have been of clinical interest
      for almost two decades as a result of the initial finding that elevated CDT
      concentrations are associated with chronic, excessive alcohol abuse. We
      demonstrate the utility of capillary electrophoresis for examining the CDT
      sialoform profile via the direct electrophoresis of serum. The need for
      negligible preelectrophoresis sample preparation and absence of
      postelectrophoresis processing dramatically decreases analysis time compared to
      slab gel-based separations. Using a fluorocarbon-coated capillary containing a
      hydroxyethyl cellulose/borate buffer, the high resolution separation of serum
      components is effected in less than 30 min. Under these conditions, the beta
      region proteins (including transferrin) are well resolved from the alpha-2 and
      gamma zone proteins in a window where the individual transferrin sialoforms can
      be detected. The usefulness of this method is demonstrated with the
      electrophoresis of serum from subjects known to be either non-alcoholic and
      alcoholic.

PMID- 10939449
TI  - A highly sensitive method for the analysis of nitrite ions by capillary zone
      electrophoresis using water-soluble aminophenylporphyrin derivative as
      chromogenic reagent.
AB  - The water soluble 5-p-aminophenyl)-10,15,20-tris(p-sulfonatophenyl) porphyrin, 4,
      acts as an extremely efficient chromogenic reagent for the detection of very low
      amounts of nitrites. The amino group of porphyrin 4 reacts smoothly with nitrite
      in acidic conditions 0.2 M HCl) producing the corresponding diazo-porphyrin
      derivative which is stable and does not show any appreciable hydrolysis to phenol
      within 6 h. The reaction is carried out in the presence of 25 mM heptakis-(2,6-di
      O-methyl)-beta-cyclodextrin that prevents precipitation of the protonated form of
      porphyrins 4 or 5 due to the formation of strong inclusion complexes. The
      capillary zone electrophoresis of the diazoporphyrin and amino-porphyrin mixture
      shows severe peak tailing. However, symmetrical peaks can be obtained by adding 5
      mM beta-cyclodextrin to the background electrolyte (20 mM phosphate buffer, pH
      7.0). Calibration curve for nitrite analysis is linear up to 0.25 mM nitrite and
      the detection limit (at a signal-to-noise ratio of 3) has been estimated to be a
      1 microM (50 ppb) of nitrite concentration in aqueous solutions.

PMID- 10939450
TI  - Influence of ester and amide-containing surfactant headgroups on selectivity in
      micellar electrokinetic chromatography.
AB  - The selectivity differences between six anionic surfactants in micellar
      electrokinetic chromatography (MEKC) are presented and the structural influence
      of the surfactant head-group is investigated. It was determined that the
      surfactant structure can have a significant impact on retention and selectivity.
      Linear solvation energy relationships (LSERs) are used to study the role of
      solute size, polarity/polarizability, and hydrogen bonding characteristics in
      determining retention and selectivity. While both the solute size and hydrogen
      bond accepting ability were found to be the most important factors in solute
      retention, the hydrogen bonding characteristic of the solutes have the largest
      influence on selectivity differences between surfactants.

PMID- 10939451
TI  - Enantiomeric separation of alanyl and leucyl dipeptides by capillary
      electrophoresis with cyclodextrins as chiral selectors.
AB  - Eight neutral cyclodextrins were tested for the enantiomeric separation of alanyl
      and leucyl dipeptides by capillary electrophoresis at pH 3, and seven out of the
      eight cyclodextrins proved suitable for the separation of one or more of the
      dipeptide enantiomer pairs. The best results were obtained with heptakis(2,6-di-O
      methyl)-beta-cyclodextrin. The dipeptides that were separated were mainly the
      aromatic and the more lipophilic aliphatic dipeptides. Mobility difference plots
      at pH 3.0 with malonic acid-triethanolamine as background electrolyte showed that
      the aromatic dipeptides had higher affinities for the cyclodextrin than the
      nonpolar, aliphatic dipeptides. The results suggested that, under the conditions
      applied, the C-terminal amino acid rather than the N-terminal one is involved in
      the chiral discrimination.

PMID- 10939452
TI  - Development of a capillary zone electrophoresis method for the separation of a
      furan combinatorial library.
AB  - Nine component mixtures of a furan library were simultaneously separated by
      capillary zone electrophoresis (CZE) using a phosphate buffer as a background
      electrolyte at low pH. The effects of buffer concentration, buffer pH, type and
      concentration of organic solvents on the electrophoretic mobility, resolution,
      and analysis time were systematically investigated. Resolution and efficiency of
      furan library components were further improved using cyclodextrin (CD)-modified
      CZE. Under optimum conditions, eight of the nine furans were baseline-resolved in
      less than 10 min at 30 kV using 50 mM phosphate buffer, 10% v/v acetonitrile
      (ACN), pH 2.0, with 5 mM gamma-CD.

PMID- 10939453
TI  - Separation of diadenosine polyphosphates by capillary electrophoresis.
AB  - The influence of buffer composition and pH on the electrophoretic behavior of
      diadenosine polyphosphates with a phosphate chain ranging from two to five
      phosphate groups has been examined. The electrophoretic mobility in carbonate
      buffer increases according to the number of phosphates, whereas in borate buffer
      the mobility changes in an irregular way as a function of pH. This finding can be
      rationalized by a well-known interaction of borate with ribose rings, which
      modifies the charge and the hydrodynamic radius of each diadenosine polyphosphate
      in a different way. Our study shows that the best separation of diadenosine
      polyphosphates can be achieved at the highest pH values of the range examined
      both in borate and carbonate buffers.

PMID- 10939454
TI  - Capillary electrophoresis separation of vinpocetine and related compounds:
      prediction of electrophoretic mobilities in partly aqueous media.
AB  - Offord's equation, a relationship between electrophoretic mobility and charge,
      size and shape of peptides, has been extended to quantitate the electrophoretic
      mobility of vinca alkaloids. Partly aqueous protonation constants and the derived
      theoretical mobilities have been proven to be able to predict experimental
      electrophoretic mobilities. In practice, seven vincamine derivatives of very low
      water-solubility were separated by capillary electrophoresis. Buffer total
      concentration, apparent pH and methanol content, the three most important
      parameters of the running buffer, were used in triangular resolution mapping to
      characterize separation. Even though electrophoresis is well known to slow down
      in partly aqueous media, under our optimized circumstances a baseline separation
      was achieved within 8 min in each case.

PMID- 10939455
TI  - Separation of a group of N-phenylpyrazole derivatives by micellar electrokinetic
      chromatography: application to the determination of solute-micelle association
      constants and estimation of the hydrophobicity.
AB  - Micellar electrokinetic chromatography (MEKC) was applied to the separation of a
      group of N-phenylpyrazole derivatives. Sodium dodecyl sulfate (SDS) as micellar
      system and 2-(N-cyclohexylamino)ethanesulfonic acid (CHES) as separation buffer
      (pH 10) were employed in the absence and presence of different percentages of
      medium chain alcohols (n-propanol or n-butanol). The separation of multicomponent
      mixtures of the solutes studied enabled the rapid determination of their
      retention factors which, in turn, allowed the study of the separation selectivity
      of compounds and the determination of their solute-micelle association constants
      (from the linear variation of the retention factors as a function of the total
      surfactant concentration in the separation buffer). Separation selectivity was
      studied according to the elution range and number of solutes separated in all the
      electrolyte solutions employed (45 micellar phases). The effect of the buffer
      concentration (0.05, 0.08 and 0.10 M), the alcohol nature (n-propanol or n
      butanol) and the alcohol percentage (1, 3 or 5%) of the values obtained for the
      solute-micelle association constants was also studied. The best separation (12
      solutes) was performed when a 0.08 M CHES buffer, pH 10, 0.02 M SDS modified by
      5% n-butanol was used. The possibilities of using MEKC for evaluating the
      hydrophobicity of compounds was investigated through the study of the correlation
      between the logarithm of the retention factors of N-phenylpyrazole derivatives
      and their logarithm of the octanol-water distribution coefficients estimated by
      high performance liquid chromatography (HPLC).

PMID- 10939456
TI  - Quality control of benserazide-levodopa and carbidopa-levodopa tablets by
      capillary zone electrophoresis.
AB  - In modern practice, the treatment of Parkinson's disease and syndrome is carried
      out using pharmaceutical formulations containing a combination of levodopa and a
      decarboxylation inhibitor (carbidopa or benserazide). Two pharmaceutical
      formulations were quantified by capillary zone electrophoresis using two
      procedures which differed only in the kind of background electrolyte used. One
      procedure used a 25 mM phosphate buffer, pH 2.5, while the second one used a 25
      mM borate buffer, pH 8.5. The electrophoretic analysis was carried out using an
      uncoated fused- silica capillary, a separation voltage of 20 kV with currents
      typically less than 60 microA, and spectrophotometric detection at 205 nm.
      Calibration curves were performed for levodopa (concentration range 1-100
      microg/mL), for carbidopa and benserazide (1-50 microg/mL), and the plots of the
      peak area versus concentration were found to be linear with a correlation
      coefficient better than 0.9990. Satisfactory results were obtained when
      commercial tablets were analyzed in terms of accuracy (98-102%), repeatability
      (0.6-2.0%), and intermediate precision (1.1-2.6%).

PMID- 10939457
TI  - Analysis of plasma protein adsorption onto polystyrene particles by two
      dimensional electrophoresis: comparison of sample application and isoelectric
      focusing techniques.
AB  - Two-dimensional electrophoresis (2-DE) was previously established for analysis of
      plasma protein adsorption patterns on particulate carriers for intravenous drug
      targeting. This study addresses a possible effect of polymeric particles on
      protein separation in the first dimension, e.g., hindrance of protein entry into
      the gel or interaction of particles with the gel matrix. Polystyrene beads of
      mean diameter 100, 200 and 1000 nm were used as model carriers. Two different
      separation techniques were performed in the first dimension of 2-DE to study
      possible interactions of the beads with the different gel matrices, i.e., carrier
      ampholytes (CA) and immobilized pH gradients (IPGs). Comparison of gels obtained
      from samples including the particles from samples separated from the polystyrene
      beads showed no noteworthy differences. Therefore, a negative effect of the
      particles can be excluded, and particle separation from the sample is not
      necessary. Another goal of this study was the transfer of analytical protocols
      for isoelectric focusing from CA to IPGs with regard to enhanced reproducibility,
      faster sample processing, and easier handling. Transfer from CA to IPGs was
      carried out successfully and showed improved resolution of basic proteins. In
      contrast to that, lower amounts of a few high molecular mass proteins were
      detected, especially when sample application cups were employed. A qualitative
      change in the obtained protein pattern was not observed. Increased entry of high
      molecular weight proteins was achieved by in-sample rehydration instead of using
      sample cups.

PMID- 10939458
TI  - Identification of the smooth muscle-specific protein, sm22, as a novel protein
      kinase C substrate using two-dimensional gel electrophoresis and mass
      spectrometry.
AB  - We report a novel method to identify protein kinase C (PKC) substrates. Tissue
      lysates were fractionated by ion exchange chromatography and used as substrates
      in in vitro kinase reactions. The phosphorylated proteins were separated using
      two-dimensional gel electrophoresis. Spots that contained isolated
      phosphoproteins were excised and digested with trypsin. The tryptic peptides were
      analyzed using mass spectrometry. While several of the proteins identified using
      this technique represent known PKC substrates, we identified a new PKC substrate
      in the initial screen. This protein, sm22, is expressed in smooth muscle cells
      and served well as a substrate for PKC in vitro. Sm22 is predominantly associated
      with the actin cytoskeleton. Upon activation of PKC in vivo, sm22 dissociates
      from the actin cytoskeleton and is distributed diffusely in the cytoplasm. Our
      data strongly suggest that phosphorylation by PKC controls the intracellular
      localization of sm22. This demonstrates that our approach, using a complex
      mixture of proteins as in vitro kinase substrates and subsequently identifying
      the newly phosphorylated proteins by mass spectrometry, is a powerful method to
      identify new kinase substrates.

PMID- 10939459
TI  - A comparative investigation into the effect of chronic alcohol feeding on the
      myocardium of normotensive and hypertensive rats: an electrophoretic and
      biochemical study.
AB  - We investigated whether the imposition of chronic alcohol in hypertension leads
      to greater biochemical and cellular abnormalities of the myocardium than those
      arising in normotension. Fifteen-week-old spontaneously hypertensive rats (SHR)
      and Wistar Kyoto (WKY) rats were fed ethanol-containing diets for six weeks.
      Particular attention was focused on the composition of contractile proteins
      identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS
      PAGE), fractional rate of protein synthesis, and synthesis rates relative to RNA
      (RNA activity) or DNA (cellular efficiency). In addition, myocardial enzymes and
      adenine nucleotides were measured. In both SHR and WKY rats chronic ethanol
      caused a general decrease in the contents of all nine contractile proteins with
      myosin heavy chain predominantly affected. Fractional rates of mixed (i.e.,
      total) and myofibrillary proteins remained unaltered in both WKY rats and SHR, as
      were cellular efficiencies. The RNA activity was significantly reduced in ethanol
      treated SHR but not in WKY rats. In ethanol-treated SHR, cardiac creatine kinase
      (CK) and malate dehydrogenase (MDH) activities were increased, AMP levels were
      elevated, whilst ATP levels and the energy charge were reduced. In WKY rats, the
      only significant change related to increased aspartate aminotransferase
      activities in response to alcohol feeding. Although there were only subtle
      differences between the response of the normotensive and hypertensive rats due to
      ethanol dosage, the reduced ATP levels and increased CK and MDH activities in SHR
      may reflect a greater susceptibility to ischaemic damage. Reduced contractile
      protein content, particularly myosin heavy chain, may contribute to contractile
      defects, a common feature of subclinical and clinical alcoholic cardiomyopathy.

PMID- 10939460
TI  - The diversity of antigen-specific antibodies in humans and in two xenochimeric
      SCID mouse models.
AB  - We applied two-dimensional gel electrophoresis (2-DE) to study the repertoire of
      tetanus toxoid (TT)-specific antibodies produced after TT immunization in healthy
      humans and in severe combined immunodeficient mice xenotransplanted with either
      human peripheral blood leukocytes (PBLe) or with human adult tonsil (hu-ton)
      pieces. Specific anti-TT antibodies, as well as total immunoglobulins (Ig), were
      purified by affinity chromatography on TT-Sepharose or Protein G-Sepharose,
      respectively. 2-DE unambiguously allowed us to differentiate between the specific
      humoral responses produced either by humans or by the two xenochimeric mouse
      models. Anti-TT antibodies produced by humans were polyclonal with a superimposed
      oligoclonality that was donor-dependent and that did not change upon time. By
      contrast, immunized hu-PBLe-SCID mice exhibited an evident clonal restriction of
      the Ig, which increased with time after boosting. Hu-ton-SCID mice showed a
      clonal diversity which was intermediate between those observed in humans and in
      hu-PBLe-SCID mice, and which was stable over time. In addition, information was
      gained by 2-DE, correlating with data obtained by enzyme-linked immunosorbent
      assay (ELISA), on the isotype composition of the anti-TT IgM response.
      Altogether, our results clearly demonstrated that the clonal diversity of
      monospecific antibodies can be appreciated by 2-DE, and that the largest
      diversity was found in humans when compared to that in xenochimeric models. In
      addition, mice implanted with pieces of lymphoid organs had the broadest anti-TT
      Ig diversity, an observation supporting the use of this model for the generation
      of antibodies with restricted specificity.

PMID- 10939461
TI  - Two-dimensional electrophoresis reveals differential protein expression in high-
      and low-secreting variants of the rat basophilic leukaemia cell line.
AB  - The aim of this investigation was the identification of cellular proteins that
      confer a high secretory phenotype on subclones of the rat basophilic leukaemia
      (RBL) cell line as a model of mast cell regulated degranulation. Following
      protein separation by two-dimensional (2-D) electrophoresis and silver staining,
      more than 2000 polypeptide "spots" were resolved reproducibly. Higher sample
      loads and Coomassie blue staining facilitated the identification by delayed
      extraction-matrix-assisted laser desorption/ionization (DE-MALDI) mass
      spectrometry of several polypeptides that were differentially expressed in the
      high- and low-secreting clones. Several proteins were identified whose expression
      could contribute to the difference in secretory phenotype. Furthermore, silver
      stained 2-D gel patterns suggested differential expression of proteins in the 20
      25 kDa and the pI 4.5-7.5 range, characteristic of small guanosine 5'
      triphosphate (GTP)-binding proteins. By a combination of "GTP overlay" and
      immunoblotting, we were able to demonstrate differential expression of small GTP
      binding-proteins, including Rab3 proteins, in high-and low-secreting clones. The
      sensitivity of this complementary approach facilitated the detection of some GTP
      binding and Rab3 proteins, whose expression was not evident in silver-stained 2-D
      gels.

PMID- 10939462
TI  - Two-dimensional electrophoresis of soluble leaf proteins, isolated from two wheat
      species (Triticum durum and Triticum aestivum) differing in sensitivity towards
      NaCl.
AB  - Plants of two wheat species (Triticum aestivum cv. Tanit and T. durum cv. Ben
      Bachir), differing in their sensitivity to NaCl were cultivated in the presence
      or absence of 100 mM NaCl for 21 days. Soluble proteins extracted from leaves
      were analyzed by two-dimensional electrophoresis in order to detect NaCl-induced
      changes in the polypeptide patterns. In all, 500 spots were detected. Results
      showed species-dependent differences. The greatest alterations in the polypeptide
      profiles following salt stress were found in the most sensitive cultivar: among
      the 12 spots (molecular mass, 15-31 kDa) specifically considered in the acidic
      region of the gel, 11 declined, even disappeared in the NaCl-sensitive leaf
      profiles, while in the tolerant species only five spots were affected by the salt
      treatment and five remained untouched; moreover in the latter, two new
      polypeptides were shown to be induced by NaCl.

PMID- 10939464
TI  - Recent developments in electrophoresis and analytical techniques. Proceedings of
      a conference. Rouen, France, 24-26 November 1999.

PMID- 10939463
TI  - Role of jasmonate in the rice (Oryza sativa L.) self-defense mechanism using
      proteome analysis.
AB  - Exogenously applied jasmonic acid (JA) was used to study changes in protein
      patterns in rice (Oryza sativa L.) seedling tissues, to classify these changes,
      and to assign a role for these changes, in order to define the role of JA in the
      rice self-defense mechanism. High resolution two-dimensional polyacrylamide gel
      electrophoretic analysis revealed induction of new proteins in both leaf and stem
      tissues after JA treatment, with the major protein spots further analyzed through
      N-terminal and internal amino acid sequencing, purification, antibody production,
      and immunoblot analysis. JA treatment results in necrosis in these tissues, which
      is accompanied by drastic reductions in ribulose-1,5-bisphosphate
      carboxylase/oxygenase (RuBisCO) subunits, and was confirmed using immunoblotting.
      Induction of novel proteins was found particularly in the stem tissues, including
      a new basic 28 kDa Bowman-Birk proteinase inhibitor protein (BBPIN; jasmonate
      induced stem protein, JISP 6), and acidic 17 kDa pathogenesis-related class 1
      protein (PR-1, JISP 9). This induction of proteins was blocked by a protein
      synthesis inhibitor cycloheximide (CHX) indicating de novo protein synthesis.
      Kinetin (KIN), a cytokinin and free radical scavenger reversed RuBisCO decreases,
      but not induction of proteins. Immunoblot analysis using antibodies generated
      against these purified proteins revealed a tissue-specific expression pattern and
      time-dependent induction after JA treatment. Our results indicate that jasmonate
      affects defense-related gene expression in rice seedlings, as evidenced by de
      novo synthesis of novel proteins with potential roles in plant defense.

PMID- 10939465
TI  - Optimised separation of endogenous urinary components using cyclodextrin-modified
      micellar electrokinetic capillary chromatography.
AB  - In this study both native and chemically modified cyclodextrins (CDs) were
      investigated as buffer additives to improve the micellar electrokinetic capillary
      chromatography (MEKC) separation of endogenous bioanalytes in human urine. The
      following CDs were investigated: alpha, beta, gamma-CDs; hydroxypropyl-alpha-CD,
      hydroxypropyl-beta-CD, methylated beta-CD, sulphated beta-CD, sulphobutyl ether
      beta-CD and hydroxypropyl-gamma-CD. The separations were compared to MEKC without
      additives. The best improvement in peak resolution and separation of urine
      components was observed with the sulphated beta-CD. A four-factor three-level
      full factorial design study was conducted on voltage, temperature, pH and
      sulphated beta-CD molarity. The optimum conditions were 25 mM sodium tetraborate,
      pH 9.5, 75 mM sodium dodecyl sulphate (SDS) and 6.25 mM sulphated beta-CD and
      were able to resolve 70 peaks from a urine pool in 12 min. These optimum
      conditions have been successfully applied to a number of clinical samples.

PMID- 10939467
TI  - Characterization by two-dimensional gel electrophoresis of host proteins whose
      synthesis is sustained or stimulated during the course of herpes simplex virus
      type 1 infection.
AB  - Herpes simplex virus type 1 (HSV-1) gene expression is concomitant with a
      selective shutoff of host protein synthesis. While the synthesis of the vast
      majority of cellular proteins is inhibited immediately after infection, several
      cellular proteins continue to be synthesized, even during the late phase of
      infection. Because these cellular proteins may intervene in the life cycle of the
      virus, we undertook two-dimensional polyacrylamide gel electrophoresis (2-D PAGE)
      analyses to evaluate the proportion of cellular proteins that is represented by
      these particular proteins. Human cells were infected with HSV-1. At different
      times after infection, proteins were labeled with 35S just prior to harvesting.
      The rate of synthesis of a set of 183 acidic host proteins, as well as that of
      ribosomal proteins, was measured during the course of infection, after separation
      by 2-D PAGE. As expected, HSV-1 induces a strong inhibition of host protein
      synthesis immediately after infection. However, the synthesis of basic ribosomal
      proteins and that of an unexpected high proportion of the sub-set of cellular
      proteins analyzed is sustained or stimulated during HSV-1 infection. A 2-D PAGE
      analysis outlining the expression patterns of these proteins at different times
      of infection is presented.

PMID- 10939466
TI  - Background-free, high sensitivity staining of proteins in one- and two
      dimensional sodium dodecyl sulfate-polyacrylamide gels using a luminescent
      ruthenium complex.
AB  - SYPRO Ruby dye is a permanent stain comprised of ruthenium as part of an organic
      complex that interacts noncovalently with proteins. SYPRO Ruby Protein Gel Stain
      provides a sensitive, gentle, fluorescence-based method for detecting proteins in
      one-dimensional and two-dimensional sodium dodecyl sulfate-polyacrylamide gels.
      Proteins are fixed, stained from 3h to overnight and then rinsed in deionized
      water or dilute methanol/acetic acid solution for 30 min. The stain can be
      visualized using a wide range of excitation sources commonly used in image
      analysis systems including a 302 nm UV-B transilluminator, 473 nm second harmonic
      generation (SHG) laser, 488 nm argon-ion laser, 532 nm yttrium-aluminum-garnet
      (YAG) laser, xenon arc lamp, blue fluorescent light bulb or blue light-emitting
      diode (LED). The sensitivity of SYPRO Ruby Protein Gel Stain is superior to
      colloidal Coomassie Brilliant Blue (CBB) stain or monobromobimane labeling and
      comparable with the highest sensitivity silver or zinc-imidazole staining
      procedures available. The linear dynamic range of SYPRO Ruby Protein Gel stain
      extends over three orders of magnitude, which is vastly superior to silver, zinc
      imidazole, monobromobimane and CBB stain. The fluorescent stain does not contain
      superfluous chemicals (formaldehyde, glutaraldehyde, Tween-20) that frequently
      interfere with peptide identification in mass spectrometry. While peptide mass
      profiles are severely altered in protein samples prelabeled with monobromobimane,
      successful identification of proteins by peptide mass profiling using matrix
      assisted laser desorption/ionization mass spectrometry was easily performed after
      protein detection with SYPRO Ruby Protein Gel stain.

PMID- 10939469
TI  - Phenotyping apolipoprotein E*3-leiden transgenic mice by two-dimensional
      polyacrylamide gel electrophoresis and mass spectrometric identification.
AB  - Apolipoprotein E (ApoE) plays an important role in cholesterol and triglyceride
      metabolism, being one of the major structural components of chylomicrons and very
      low density lipoprotein (VLDL) remnants. ApoE functions as a ligand in the
      receptor-mediated uptake of these remnants from the blood by the liver. A variant
      form of ApoE, apolipoprotein E*3-Leiden, shows reduced affinity for the low
      density lipoprotein (LDL) receptor, and results in the dominant expression of
      type III hyperlipoproteinemia. Two-dimensional electrophoresis (2-DE) has been
      used to characterise protein expression in serum samples from control and
      transgenic mice expressing the human ApoE*3-Leiden mutation, fed a cholesterol
      rich diet, and transgenic mice fed a normal diet. For the identification of
      proteins, single silver-stained spots were excised from the 2-DE gels and
      subjected to in-gel enzymatic digestion. Extracted peptides were analysed by
      matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF-MS). This proteomic approach has enabled the ApoE*3-Leiden variant to
      be positioned in a 2-DE separation of serum proteins, and has identified changes
      in the expression of haptoglobin, indicating that this protein may provide a
      marker for the potential onset of atherosclerosis.

PMID- 10939470
TI  - Towards a proteomic map of Lactococcus lactis NCDO 763.
AB  - Lactococcus lactis is a widely used bacteria in dairy industry, specially in
      cheese ripening. Numerous lactococcal enzymes and proteins are involved in this
      process. Proteomics makes it possible to deal with a high number of proteins and
      identify modification of their patterns in two-dimensional (2-D) gels. However,
      an annotated reference map is necessary prior to analyzing protein variations. We
      have begun to construct such a map in easily reproducible conditions and identify
      proteins.

PMID- 10939468
TI  - Two-dimensional electrophoresis and mass spectrometry identification of proteins
      bound by a murine monoclonal anti-cardiolipin antibody: a powerful technique to
      characterize the cross-reactivity of a single autoantibody.
AB  - Antigenic cross-reactivity, i.e., the capacity of a single antibody to react with
      apparently dissimilar structures, is a common characteristic of autoantibodies
      produced during systemic lupus erythematosus (SLE), an autoimmune disease
      developed by humans and certain strains of mice. Characterization of the extent
      of cross-reactivity of SLE-related autoantibodies may help identify the
      immunogenic stimulus, or stimuli, of autoantibody-secreting B-lymphocytes. Two
      dimensional polyacrylamide gel electrophoresis (2-D PAGE) was combined with mass
      spectrometry (MS) to identify cell proteins recognized by a single monoclonal
      autoantibody (mAb 4B7), derived from an (NZW x BXSB)F1 mouse and selected based
      on its capacity to react with cardiolipin, that binds to elements in the
      cytoplasm and nucleoli of HEp-2 cells as assessed by indirect immunofluorescence
      assay. Proteins from HL-60 extract were separated by 1-D and 2-D PAGE. Western
      blotting with mAb 4B7 after SDS-PAGE revealed four bands, two intensely labeled
      at 35 and 32 kDa, and two weaker ones at 20 and 60 kDa; three spots were detected
      after 2-D PAGE. After trypsin in-gel digestion of the three protein spots, MS
      yielded representative matrix assisted laser desorption/ionization-time of flight
      (MALDI-TOF) Reflector or quadrupole-time of flight (Q-TOF) spectra. The three
      corresponding proteins were identified as the nucleolar phosphoprotein B23
      (nucleophosmin), heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2) and the 60
      kDa Ro/SS-A RNP. Thus, these results showed that 2-D PAGE combined with MS
      constitutes a sensitive and powerful technique to characterize the full extent of
      cross-reactivity of a single mAb and may constitute a new approach to further
      characterize the immunogenic cellular components involved in the breakage of B
      cell tolerance observed in SLE.

PMID- 10939471
TI  - Monitoring the N-glycosylation of plant glycoproteins by fluorophore-assisted
      carbohydrate electrophoresis.
AB  - We have evaluated the efficiency of a fast, simple and efficient method,
      fluorophore-assisted carbohydrate electrophoresis (FACE), for the
      characterization of plant N-linked glycans. After their enzymatic release from
      plant glycoproteins, N-glycans were reductively aminated to the charged
      fluorophore 8-aminonaphthalene-1, 3, 6-trisulfonic acid (ANTS) and separated
      using high resolution polyacrylamide gel electrophoresis. In addition, an
      affinity purification procedure using concanavalin A was developed for separation
      of ANTS-labeled high-mannose-type N-glycans from other plant oligosaccharides.

PMID- 10939472
TI  - Identification of stress-inducible proteins in Lactobacillus delbrueckii subsp.
      bulgaricus.
AB  - Lactobacillus delbrueckii subsp. bulgaricus (L. bulgaricus) is a homofermentative
      bacterium that produces lactic acid during growth. We adapted the two-dimensional
      electrophoresis (2-DE) technique to study the response of this bacterium to
      acidity. De novo protein synthesis was monitored by [35S]methionine labeling of
      exponentially growing cultures under standard (pH 6) and acidic (pH 4.75)
      conditions. After 2-DE separation, the protein patterns were compared. The
      protein spots showing increased radioactivity levels under acid conditions were
      considered acid-induced. We determined the N-terminal amino acid sequence of
      three highly induced proteins; comparing these proteins to databases we
      identified them to be the well-known heat shock proteins GroES, GroEL, and DnaK.
      Their induction levels were measured and compared. This is the first study by 2
      DE of stress response in L. bulgaricus. We established the method and present a
      protein map which will be useful for future studies.

PMID- 10939473
TI  - Analysis by two-dimensional electrophoresis of the effect of salt stress on the
      polypeptide patterns in roots of a salt-tolerant and a salt-sensitive cultivar of
      wheat.
AB  - The effect of salt stress on the polypeptide levels in roots of two wheat
      (Triticum durum) cultivars with different sensitivity to NaCl (cv. Ben Bachir,
      sensitive; cv. Chili, tolerant), was examined by two-dimensional polyacrylamide
      gel electrophoresis. Blue-stained gels were analyzed by visual inspection to
      identify changes that resulted when seedlings were grown in the presence of 200
      mM NaCl for four days. Although the protein patterns for control and salt
      stressed seedlings were qualitatively similar, the net synthesis of a 26 kDa
      polypeptide was significantly changed. This observation was mainly noticeable in
      the more tolerant cultivar. With the intention of identifying its function, the
      NH2-terminal of this polypeptide was sequenced. A 20 amino acid sequence was
      obtained and compared to sequences available in different databases. Possible
      roles of this polypeptide, depending on the homologies of its amino acid sequence
      with known proteins, in salinity tolerance are discussed.

PMID- 10939475
TI  - Occurence of subtelomeric rearrangements in the genome of the microsporidian
      parasite Encephalitozoon cuniculi, as revealed by a new fingerprinting procedure
      based on two-dimensional pulsed field gel electrophoresis.
AB  - In Microsporidia, mitochondria-lacking eukaryotic intracellular parasites,
      genomic comparisons were so far based on molecular karyotyping. The mammal
      infecting species Encephalitozoon cuniculi is characterized by a very low haploid
      genome size (approximately 2.8 Mbp) and rather high karyotype variability.
      Recently, we developed a two-dimensional pulsed field gel electrophoresis (2-D
      PFGE) fingerprinting technique useful for constructing a restriction map fo the
      genome of a mouse E. cuniculi isolate (karyotype variant A). The so-called
      karyotype and restriction display 2-D PFGE (KARD-PFGE) protocol involved 1-D
      chromosome separation, digestion with a rare cutter, Klenow radiolabeling of
      genomic DNA and 2-D separation of restriction fragments followed by
      autoradiography. In order to assess its suitability for detecting polymorphic
      loci in E. cuniculi, we applied KARD-PFGE with either BssHII or Mlul digestion to
      genome analysis of two rabbit isolates representative of two different karyotype
      variants (A and C). The 2-D spot pattern of the rabbit isolate variant A is
      identical to the reference mouse isolate but differs greatly from the rabbit
      isolate variant C. Chromosomal restriction fragment length polymorphisms (RFLPs)
      provide strong evidence for homologous chromosomes and frequent DNA
      rearrangements within subtelomeric regions just upstream of the dispersed rDNA
      units closely associated with each chromosomal end.

PMID- 10939474
TI  - Protein analysis by mass spectrometry and sequence database searching: a
      proteomic approach to identify human lymphoblastoid cell line proteins.
AB  - Lymphoblastoid cell lines correspond to in vitro EBV-immortalized lymphocyte B
      cells. These cells display a suitable model for experiments dealing with changes
      in protein expression occurring upon B-cell differentiation, after drug
      treatment, or after inhibition of some transcription factors. For all these
      reasons we have undertaken an effort aimed at developing a hematopoietic cell
      line protein two-dimensional electrophoresis (2-DE) database, containing B
      lymphoblastoid 2-DE maps. In this work, matrix-assisted laser
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) peptide
      mass fingerprinting analysis was adopted for protein identification. The peptide
      mass fingerprinting identification and the sequence coverage obtained on
      colloidal Coomassie blue (CBB) stained gel was close to that obtained using zinc
      imidazole staining. Everything considered, CBB being more comfortable for
      subsequent spot manipulations, CBB staining was chosen for identification of a
      larger number of polypeptides. The results suggest that reticulation of the gel
      can interfere preventing the uptake of the enzyme during the in-gel digestion
      step. Consequently, low molecular mass proteins appear more difficult to identify
      by mass fingerprinting. Finally, the information provided in this study allows
      the construction of a new annoted reference map of human lymphoblastoid cell
      proteins. Among the identified proteins 60% were not yet positioned on 2-DE maps
      in three of the most important well-documented databases. The annoted map will be
      accessible via Internet on the LBPP server at URL:http:// www-smbh.univ
      paris13.fr/lbtp/index.htm.

PMID- 10939476
TI  - Electrophoresis education on-line: initiation of a virtual network.

PMID- 10939477
TI  - MR relaxometry of lumbar spine, hip, and calcaneus in healthy premenopausal
      women: relationship with dual energy X-ray absorptiometry and quantitative
      ultrasound.
AB  - This study evaluates if the reversible transverse relaxation rate (R2') assessed
      in vivo by MR of lumbar vertebrae, hip, and calcaneus is correlated with dual
      energy X-ray absorptiometry (DXA) and to quantitative ultrasound (QUS) of the
      calcaneus. Fifteen healthy premenopausal women aged 23-47 years were studied by
      DXA, QUS, and MR relaxometry. The GESFIDE sequence was used to separate the FID
      rate (R2*) into its two components, the non-reversible transverse relaxation rate
      (R2) and the reversible transverse relaxation rate (R2'). Long-term
      reproducibility was obtained by repeated measurements of hip and calcaneus in
      nine individuals after 300+/-89 days. R2' and R2* of the calcaneus had a
      relationship to broad-band ultrasound attenuation (BUA; r = 0.46, both p<0.05),
      but not to other US or DXA parameters of the calcaneus. Both R2' and R2* were
      correlated with bone mineral per area (BMA) of the hip (r>0.73, p<0.001 and
      r>0.66, p<0.01, respectively). R2 was correlated with BMA(L1-L4) (r = 0.52,
      p<0.05). R2' and R2* were not correlated with BMA(L1-L4). When the right and left
      sides were compared in calcaneus and hip the correlation coefficient for R2' and
      R2* ranged from 0.76 to 0.86 (p<0.001). The long-term reproducibility expressed
      in coefficient of variation (CV%) was approximately 5 % for R2' and approximately
      4% for R2*. Differences in R2 between individuals were not reproducible. The
      results of this study indicate that R2' and R2* measurements are reproducible and
      might be of value when evaluating bone quality of the hip and foot.

PMID- 10939478
TI  - Short-TE projection reconstruction MR microscopy in the evaluation of articular
      cartilage thickness.
AB  - The aim of this study was to assess the potential of projection-reconstruction
      (PR) MR microscopy in the accurate measurement of cartilage thickness. Short-TE
      PR microimages were acquired at 7.05 T on bone-cartilage cylindrical plugs
      excised from four regions of two disarticulated femoral heads (i. e. superior,
      inferior, posterior and anterior), using an NMR instrument equipped with a
      microimaging accessory. The PR microimages were then correlated with conventional
      spin-echo (SE) microimages and with histology. On PR microimages, acquired with
      an echo time of 3.2 ms, the cartilage signal was increased, allowing an accurate
      delineation of the cartilage from the tidemark/cortical bone region. As a
      consequence, by the PR method a more precise measurement of cartilage thickness
      compared with that performed by the conventional SE approach was feasible. An
      excellent correlation between PR microimages and histology was also obtained (r =
      0.90). By the proposed method it is possible to accurately determine the
      cartilage thickness better than with the conventional SE sequences.

PMID- 10939479
TI  - Comparison between standard radiography and spiral CT with 3D reconstruction in
      the evaluation, classification and management of tibial plateau fractures.
AB  - The aim of this study was to compare the diagnostic efficiency of plain film and
      spiral CT examinations with 3D reconstructions of 42 tibial plateau fractures and
      to assess the accuracy of these two techniques in the pre-operative surgical plan
      in 22 cases. Forty-two tibial plateau fractures were examined with plain film
      (anteroposterior, lateral, two obliques) and spiral CT with surface-shaded
      display 3D reconstructions. The Swiss AO-ASIF classification system of bone
      fracture from Muller was used. In 22 cases the surgical plans and the sequence of
      reconstruction of the fragments were prospectively determined with both
      techniques, successively, and then correlated with the surgical reports and post
      operative plain film. The fractures were underestimated with plain film in 18 of
      42 cases (43%). Due to the spiral CT 3D reconstructions, and precise pre
      operative information, the surgical plans based on plain film were modified and
      adjusted in 13 cases among 22 (59%). Spiral CT 3D reconstructions give a better
      and more accurate demonstration of the tibial plateau fracture and allows a more
      precise pre-operative surgical plan.

PMID- 10939480
TI  - Intra-articular ganglion cysts of the cruciate ligaments.
AB  - Intra-articular ganglion cysts of the cruciate ligaments are associated with non
      specific clinical signs and symptoms. Familiarity with the MR appearances in
      particular is important to make an accurate diagnosis, exclude associated
      abnormalities, and avoid misdiagnosis.

PMID- 10939481
TI  - CT-guided percutaneous laser disc decompression with Ceralas D, a diode laser
      with 980-nm wavelength and 200-microm fiber optics.
AB  - The aim of this study was to evaluate the compact, portable Ceralas-D diode laser
      (CeramOptec; 980 + 30 nm wavelength, 200-microm optical fiber) concerning
      clinical usefulness, handling, and clinical results in the CT-guided treatment of
      herniated lumbar discs. The positioning of the canula in intradiscal space, the
      placement of the laser fiber into the disc through the lying canula, and the
      vaporization itself were carried out under CT-guidance. Due to the thin fiber
      optic, it was possible to use a thin 23-gauge canula. The laser procedure was
      performed in 0.1- to 1-s shots with 1-s pulse pause and 4-W power output. A total
      of 1650-2300 J was applied on each percutaneous laser disc decompression (PLDD).
      Results in 26 patients were established with a visual-analogue scale (VAS). On
      the follow-up examinations, 46% of the patients were absolutely pain free ( > 85
      % VAS) and fully active in everyday life after 4 postoperative weeks. Thirty-one
      percent of patients were relieved of the leg pain but had occasional back pain
      without sensorimotor impairment. Fifteen percent sensed a slight alleviation ( >
      50% VAS) of the radiate pain. Eight percent did not experience radicular or
      pseudo-radicular pain alleviation (< 25% VAS). Cerales-D proves to be an
      efficient tool for CT-guided PLDD on non-sequestered herniated lumbar discs.

PMID- 10939482
TI  - Reversed palmaris longus muscle on MRI: report of four cases.
AB  - Muscle anomalies around the wrist, in particular the palmaris longus muscle, may
      cause effort-related median nerve compression. A search of the medical records at
      our university hospital between 1994 and 1999 revealed four patients with an
      effort-related median nerve compression due to a reversed palmaris longus muscle.
      Magnetic resonance imaging was used in the patient work-up and showed an
      anomalous muscle in each case that had been missed initially. All four patients
      were free of pain after simple excision of the anomalous muscle. Awareness of
      muscle anomalies at the wrist on MR imaging is essential in evaluating patients
      with nerve compressions at the wrist. The purpose of this article is to heighten
      this awareness in radiologists.

PMID- 10939483
TI  - Absolute renal blood flow quantification by dynamic MRI and Gd-DTPA.
AB  - The aim of this study was to demonstrate the feasibility of the absolute renal
      blood flow quantification using MRI and injection of contrast media. Using a T1
      weighted fast gradient sequence following an intravenous bolus injection of Gd
      DTPA, dynamic images of the kidney were obtained in patients with well
      functioning native kidneys (n = 7) or transplant (n = 9), with significant renal
      artery stenosis (n = 4) and with renal failure (n = 7). After signal intensity
      calibration, the absolute renal perfusion was equal to the wash-in slope of the
      renal transit curve divided by the contrast medium concentration at the peak of
      the bolus in the aorta. The cortical blood flow was 2.54+/-1.16 ml/min per gram
      in well-functioning kidneys decreasing to 1.09+/-0.75 ml/min per gram in case of
      renal artery stenosis (p = 0.04) and to 0.51+/-0.34 ml/min per gram in case of
      renal failure (P<0.001). These measurements were in agreement with previous
      results obtained by other methods. A standard MRI imaging sequence and a simple
      model can provide realistic quantitative data on renal perfusion. This work
      justifies further studies to compare this model with a gold standard for renal
      blood flow measurements.

PMID- 10939484
TI  - MR urography findings of a duplicated ectopic ureter in an adult man.
AB  - In this report we present the imaging findings in an adult male with a duplicated
      ectopic ureter which inserted into the prostatic urethra. The appearances at
      excretory urography, US, CT, and MR urography are described together with the
      potential pitfalls of the imaging techniques. Both US and MR urography accurately
      image the collecting system from the kidney to the point of distal ureteral
      insertion, and in our patient, MR urography provided similar information to US.

PMID- 10939485
TI  - Pelvic arteriovenous malformations: gadolinium-enhanced three-dimensional MR
      angiography findings.
AB  - Pelvic arteriovenous malformations (PAV-Ms) are rare disorders traditionally
      diagnosed by conventional angiography. Breath-hold three-dimensional gadolinium
      enhanced MR angiography (3D-Gd-MRA) is a state-of-the-art alternative for
      vascular imaging. We describe the 3D-Gd-MRA findings in two patients with PAVMs.
      The 3D-Gd-MRA approach provides a noninvasive and versatile method for evaluation
      of PAVMs that enables both angiographic assessment of the malformations and
      evaluation of visceral involvement, which can preclude surgical intervention.

PMID- 10939486
TI  - Primary malignant lymphoma of the urinary bladder: report of three cases and
      review of the literature.
AB  - We report three cases of a primary malignant lymphoma of the urinary bladder. The
      radiological features revealed a sessile mass of the lateral wall for one case, a
      circumferential thickening in the second, and two separated masses of the bladder
      wall in the last case. Primary malignant lymphoma of the urinary bladder is
      extremely rare. From a review of the literature, the clinical and radiological
      findings are discussed. In this paper we report the first case of urinary bladder
      lymphoma presented on CTas multiple masses.

PMID- 10939487
TI  - Granulomatous renal pseudotumor in Wegener's granulomatosis: imaging findings in
      one case.
AB  - Wegener's granulomatosis is a clinicopathological entity characterized by
      necrotizing granulomatous angiitis involving the upper- and/or lower respiratory
      tract and the kidneys. Renal involvement is usually characterized by a rapidly
      progressive necrotizing glomerulonephritis. A case is presented of a patient who
      developed renal failure and presented a solitary pseudotumoral lesion in the
      upper pole of the left kidney. Imaging characteristics on US, CT and MR imaging
      are discussed. The diagnosis was confirmed with ultrasound-guided needle biopsy.

PMID- 10939488
TI  - Radiologic spectrum of rectal stenosis.
AB  - Rectal stenosis is a common condition caused by a wide variety of diseases,
      including both intrinsic and extrinsic disorders, as well as both malignant and
      benign pathologies. Barium enema, CT, and MRI are the primary modalities for the
      evaluation of the disease, and careful observation of the characteristic
      radiologic features usually leads to correct diagnosis. However, some of the
      lesions looks very similar and are difficult to differentiate from each other.
      The purpose of this study is to review the literature on diseases that cause
      rectal stenosis, to clarify the characteristics of radiologic features, and to
      suggest the limitations in differential diagnosis. Deliberate analysis of these
      imaging features and correlation with clinical manifestations can facilitate a
      more specific diagnosis.

PMID- 10939489
TI  - Duodenal duplication cyst identified with MRCP.
AB  - We report a case of a stalked cystic duodenal duplication. The lesion,
      hyperintense on T2-weighted GRE images, maintained the signal intensity after
      oral administration of a negative contrast agent (Lumirem, Guerbet, Aulnay-Sous
      Bois, France), confirming its independence from the duodenal lumen. To our
      knowledge, this is the first demonstration of duodenal duplication by means of MR
      cholangiopancreatography.

PMID- 10939490
TI  - Ascending colonic variceal bleeding: utility of phase-contrast MR portography in
      diagnosis and follow-up after treatment with TIPS and variceal embolization.
AB  - The authors describe the discovery of ascending colonic variceal veins via
      celiomesenteric diagnostic angiography following a bout of melena in a 44-year
      old woman. Magnetic resonance imaging, including phase-contrast MR venography,
      allowed visualization of the portal and systemic veins immediately after the
      initial angiograms. The hemorrhagic episode did not resolve until after
      transjugular intrahepatic shunt insertion and selective variceal embolization
      through the shunt. At 1 week-, 3 months-, and 6 months post treatment, follow-up
      MR venography no longer revealed the presence of colonic varices. Colonoscopy at
      6 months was normal and the patient did not have any further episodes of bleeding
      until a liver transplantation was performed after 9 months.

PMID- 10939491
TI  - Late complication following percutaneous cholecystostomy: retained abdominal wall
      gallstone.
AB  - A case of recurrent abdominal wall abscess following percutaneous cholecystostomy
      (PC) is presented. Transperitoneal PC was performed in an 82-year-old female with
      calculous cholecystitis. Symptoms resolved and the catheter was removed 29 days
      later. The patient came back 5 months later with a superficial abscess that was
      drained and 8 months post PC with a fistula discharging clear fluid.
      Ultrasonography revealed the tract adjacent to an area of inflammation containing
      a calculus, whereas CT failed to depict the stone. Subsequent surgery confirmed
      US findings. To our knowledge, this is the first report of a dislodged bile stone
      following percutaneous cholecystostomy.

PMID- 10939492
TI  - Adenosarcoma arising in hepatic endometriosis.
AB  - We report a case of adenosarcoma arising in hepatic endometriosis. Both CT and MR
      scans demonstrated a huge heterogeneous mass containing septated, thick-walled
      cystic lesions. After enlarged right hepatectomy, the patient was asymptomatic
      with no abnormalities at liver and abdominal CT scan at 2-year follow-up.

PMID- 10939493
TI  - MR imaging findings in two patients with hepatic veno-occlusive disease following
      bone marrow transplantation.
AB  - The aim of this study was to describe the MRI features of veno-occlusive disease
      (VOD) following bone-marrow transplantation in two patients. The MRI features
      consisted of hepatomegaly, hepatic vein narrowing, periportal cuffing,
      gallbladder wall thickening, marked hyperintensity of the gallbladder wall on T2
      weighted images, ascites, and pleural effusion. In one patient, signs of reduced
      portal venous flow velocity were also observed. It is concluded that the use of
      MRI as a complementary technique following non-conclusive US examination enabled
      a timely diagnosis of this life-threatening disease in both patients.

PMID- 10939494
TI  - Hepatic artery aneurysm in a patient with Behcets disease and segmental
      pancreatitis developing after its embolization.
AB  - Segmental pancreatitis is an unusual form of acute pancreatitis mostly seen in
      the head of pancreas. We present the CT findings of a segmental pancreatitis in
      the body and tail of the pancreas developed following endovascular embolization
      of a giant hepatic artery aneurysm and arterioportal fistula in a patient with
      Behcet's disease.

PMID- 10939495
TI  - Thoracic helical CT: influence of subsecond scan time and thin collimation on
      evaluation of peripheral pulmonary arteries.
AB  - The objective of this study was to analyze the influence of collimation on the
      identification of peripheral pulmonary arteries on helical CT scans. Three
      hundred sixty of 370 consecutive helical CT angiograms of the pulmonary
      circulation obtained during an 18-month investigation period were considered as
      technically acceptable for the detection of acute pulmonary embolism and were
      retrospectively analyzed. Patients in group A (n = 274) underwent CT with 2-mm
      collimation and pitch of 2; those in group B (n = 86) underwent CT with 3-mm
      collimation and pitch 1.7; a 0.75-s rotation time was systematically used. A
      total of 2160 segmental (six arterial zones per patient) and 2160 subsegmental
      (six arterial zones per patient) arterial zones were assessed. Whereas the
      percentage of segmental arteries was not significantly different between group A
      (86%) and group B (89%), the percentage of analyzable subsegmental arteries was
      greater in group A (65%) than in group B (43 %) (P<0.001). The causes of
      inadequately depicted subsegmental arterial zones were partial-volume effects
      (group A, n = 302; 52%; group B, n = 197; 67%; P<0.001), suboptimal enhancement
      (group A, n = 145; 25%; group B, n = 43; 15%; P<0.05), motion artifacts (group A,
      n = 113; 20%; group B, n = 30; 10%), and unincluded arteries (group A, n = 20;
      3%; group B, n = 25; 8%). Helical CT with 2-mm collimation at 0.75 s per
      revolution enables marked improvement in the analysis of subsegmental arteries in
      routine clinical practice.

PMID- 10939496
TI  - CT bronchus sign in malignant solitary pulmonary lesions: value in the prediction
      of cell type.
AB  - The aim of this study was to evaluate differences in the prevalence of patterns
      of CT bronchus sign in malignant solitary pulmonary lesions (SPLs), according to
      their histologic cell types and with respect to size, location, and degree of
      cell differentiation. Computed tomography scans of 78 patients, in whom
      pathologically confirmed malignant SPLs with CT bronchus sign were present, were
      randomly selected and reviewed by two radiologists under consensus. All 78 were
      CT scans done using spiral technique with 10-mm collimation and 10-mm
      reconstruction intervals with enhancement, and 75 included additional high
      resolution CT scans. Lesions were classified into four cell types as squamous
      cell carcinoma (n = 24), small cell carcinoma (n = 12), adenocarcinoma (n = 23),
      bronchioloalveolar carcinoma (BAC; n = 9), and others (n = 12), into three
      degrees of differentiation, into three size groups, and according to location
      (central or peripheral). Patterns of CT bronchus sign were classified into
      abruptly obstructing (I), patent (II), displacing (III), or tapered narrowing
      (IV) types. The relationships between the patterns of CT bronchus sign and cell
      type and degree of cell differentiation were evaluated. Eighty patterns of CT
      bronchus sign were observed in 78 patients. According to cell type, squamous cell
      carcinoma showed most often type-I pattern (45.8%) but no type-II pattern, which
      was the most common pattern observed in BAC (77.8%) and adenocarcinoma (34.8%;
      p<0.01). Small cell carcinoma showed a varied distribution among the four
      patterns of CT bronchus sign. According to location, in central squamous cell
      carcinomas, type-I pattern was more common(55%; p<0.01). Bronchioloalveolar
      carcinoma showed more peripheral lesions and in both central and peripheral
      lesions, type-II pattern was significantly more common (100 and 66.7%; p<0.01).
      In SPLs with CT bronchus sign of obstructing pattern, especially if central
      location, squamous cell carcinoma should be suspected, whereas in SPLs with
      patent CT bronchus sign, regardless of the location, the strong possibility of
      BAC should be considered.

PMID- 10939497
TI  - Mediastinal lymphangioma in adults: CT and MR imaging features.
AB  - Adult mediastinal lymphangiomas are rare lesions the diagnosis of which is
      difficult based on imaging studies. A retrospective study of CT, MR, and
      pathologic findings of mediastinal lymphangioma was performed in order to
      correlate pathological and imaging findings. Nine cases of adult lymphangiomas
      were identified in the records of our institution over a 12-year period. The CT,
      MR, and pathologic findings were reviewed. Lesions were classified pathologically
      as unilocular, cavernous, and intermediate types. Pathologic examination
      identified six cases of unilocular lesion, two cases of cavernous type, and one
      intermediate type. The CT features (n = 9) included a smoothly marginated non
      enhancing mass of water attenuation (n = 7), a non-enhancing mass of soft tissue
      attenuation (n = 1), and an enhancing multiseptated mass (n = 1). Lesions were
      located in the anterior mediastinum (n = 2), right paratracheal (n = 4),
      subcarinal (n = 1), aortopulmonic window (n = 1) areas, and below the left hilum
      extending into the posterior mediastinum (n = 1). The MR features (n = 3) were
      characterized by an enhancing multicystic and multiseptated appearance, evocative
      of a cavernous type in two cases. The CT appearance of mediastinal thoracic
      lymphangioma is variable depending on the pathologic type. The most common
      unilocular type is a non-enhancing thin-walled mass on CT. A less frequent
      cavernous type can be suggested based on a multiseptated and loculated mass on CT
      and/or MR examination.

PMID- 10939498
TI  - Pulmonary vein varix: diagnosis with multi-slice helical CT.
AB  - The diagnosis of a pulmonary vein varix with a recently introduced new CT
      technology, multi-slice helical CT, is discussed. The advantage of multi-slice
      helical CT lies in increased thin-slice coverage during a single breath hold,
      which is the predominant factor limiting scan time. This CT technique facilitates
      the diagnosis of vascular pulmonary pathology.

PMID- 10939499
TI  - Spiral CT of the lung in children with malignant extra-thoracic tumors:
      distribution of benign vs malignant pulmonary nodules.
AB  - The purpose of this paper is to clarify the distribution of benign vs malignant
      pulmonary nodules which are seen on spiral CT in children with malignant extra
      thoracic solid tumors. Seventy-four children with known solid, extra-thoracic
      tumors underwent spiral CT of the chest. According to the initial and follow-up
      (interval 9.2+/-4.7 months) findings, the children were graded into four groups:
      I = normal; II = solitary nodule unchanged at follow-up; III = multiple nodules
      with one or more than one unchanged at follow-up; and IV = solitary or multiple
      nodules all changed at follow-up. Nodules without change at follow-up were
      regarded as benign. Forty-nine children did present with normal pulmonary CT
      exams. In 7 cases solitary pulmonary nodules were found unchanged (group II) at
      follow-up and in 2 cases (group III) some of the nodules were stationary. Thus,
      12% (9 of 74) presented with at least one pulmonary nodule that did not change at
      follow-up. Solitary nodules (in groups II and IV) with a diameter <5 mm were in
      70 % (7 of 10) unchanged at follow-up and regarded as benign. In children with
      known solid extra-thoracic tumors at initial presentation, 70% of solitary
      nodules ( <5 mm) may be benign. To avoid overstaging, smaller solitary nodules
      must not automatically be regarded as metastases.

PMID- 10939500
TI  - Altered energy metabolism after myocardial infarction assessed by 31P-MR
      spectroscopy in humans.
AB  - The value of 31P-magnetic resonance spectroscopy (MRS) as a possible tool to
      distinguish viable from non-viable tissue after myocardial infarction was
      analysed in humans. Fifteen patients 3 weeks after anterior myocardial infarction
      were studied with breath-hold cine MRI and 3D-CSI MRS (1.5 T system). 31P-spectra
      were obtained from infarcted as well as non-infarcted myocardium (voxel size 25
      cm3 each). Gold standard for viability was recovery of regional function, as
      determined by a control MRI 6 months after revascularization. Ten age-matched
      healthy volunteers served as control group. No significant difference was found
      between the phosphocreatine to adenosinetriphosphate (PCr/ ATP) ratio of
      volunteers (SD 1.72+/-0.31) and non-infarcted septal myocardium of patients. Cine
      MRI demonstrated recovery of regional function in 10 patients, i. e. 10 patients
      showed viable and 5 non-viable myocardium. In viable myocardium, the PCr/ATP
      ratio was 1.47+/-0.38 (non-significant vs volunteers; p>0.05). In the 5 patients
      with akinetic myocardium, PCr peaks could not be detected. Therefore, calculation
      of PCr/ATP ratios was not possible. However, a significant reduction of the ATP
      signal-to-noise ratio (SNR) was observed (2.92+/-0.73 vs 6.68+/-0.80; patients vs
      volunteers; p<0.05). The SNR of ATP of akinetic regions may predict recovery of
      function after revascularization in patients with myocardial infarction.

PMID- 10939501
TI  - Implanted central venous catheter-related acute superior vena cava syndrome:
      management by metallic stent and endovascular repositioning of the catheter tip.
AB  - We describe a case of a 49-year-old woman with stage-IIIB lung adenocarcinoma who
      experienced an acute superior vena cava syndrome related to an implanted central
      venous catheter without associated venous thrombosis. The catheter was surgically
      implanted for chemotherapy. Superior vena cava syndrome appeared after the
      procedure and was due to insertion of the catheter through a subclinical stenosis
      of the superior vena cava. Complete resolution of the patient's symptoms was
      obtained using stent placement and endovascular repositioning of the catheter
      tip.

PMID- 10939502
TI  - Radiological signs of a left atrial aneurysm.
AB  - We report a case of an acquired mid-sized extrapericardial aneurysm in the area
      of the left atrial appendage and demonstrate the diagnostic impact of several
      imaging methods. Chest radiography gave a hint to the diagnosis with a bulky mass
      of soft tissue density appearing adjacent to the left atrial appendage.
      Transthoracic as well as transesophageal echocardiography missed the origin of
      the aneurysm. Magnetic resonance imaging helped to establish the diagnosis with
      use of a coronal imaging plane. No contrast agent was necessary. Thus, the
      combination of chest X-ray and MRI provided excellent support for patient
      management.

PMID- 10939503
TI  - Glue embolization of a ruptured celiac trunk pseudoaneurysm via the
      gastroduodenal artery.
AB  - Percutaneous transcatheter embolization of splanchnic artery aneurysms is a
      minimally invasive and alternative therapy to conventional surgical intervention.
      Due to a high-grade stenosis at the origin of the celiac trunk, a retrograde
      approach to the celiac trunk pseudoaneurysm via the gastroduodenal artery was
      necessary. To prevent undesirable embolization into the peripheral left gastric
      artery initial occlusion of the central portion of the left gastric artery was
      performed with microcoils using a Tracker catheter. Complete occlusion of the
      celiac trunk itself and the short adjacent segments of the celiac artery was
      achieved by using a mixture of N-butyl-2-cyanoacrylate and ethiodized oil as the
      embolizing agent.

PMID- 10939504
TI  - Plain film, CT and MRI sensibility in the evaluation of intraorbital foreign
      bodies in an in vitro model of the orbit and in pig eyes.
AB  - Detection and characterization of intraorbital foreign bodies (IFB) is
      fundamental in acute trauma setting, preventing inflammatory sequelae or
      complications related to IFB movements when a MRI study is planned. Papers
      concerning plain film and CT sensibility in IFB detection show controversial
      results. For this reason we investigated plain film, CT and MRI sensibility in
      the evaluation of IFB. For an in vitro model, specimens of dry and fresh wood,
      glass, iron, plastic and graphite were immersed in animal lard and in a 0.9%
      sodium chloride plus 3.5 g/dl human serum albumin solution. Specimens of
      different size and nature where also implanted into enucleated pig eyes. Air
      bubbles were introduced also. Plain film, CT and MRI investigation were
      performed. Plain films underestimated intraocular IFB as plastic, fresh or dry
      wooden IFB were not demonstrated. The CT study was always able to depict and
      differentiate IFB according to the attenuation values. Severe artefacts prevented
      demonstration of iron, glass and graphite IFB on MRI, whereas plastic or wooden
      IFB were always detected. Despite radiographs have been suggested as a
      prerequisite for MR imaging, because our results showed plain film to
      underestimate radiolucent IFB, we suggest CT as the modality of choice when IFB
      has to be ruled out.

PMID- 10939505
TI  - Diffusion-weighted echo-planar MR imaging in differential diagnosis of brain
      tumors and tumor-like conditions.
AB  - We assess diffusion-weighted MR images in the differential diagnosis of
      intracranial brain tumors and tumor-like conditions. Heavily diffusion-weighted
      (b = 1100 or 1200 s/mm2) axial images were obtained with single-shot echo-planar
      technique in 93 patients with pathologically confirmed various intracranial
      tumors and tumor-like conditions with diffusion gradient perpendicular to the
      images. We compared signal intensity of the lesions with those of gray and white
      matter, and cerebrospinal fluid (CSF). In 29 cases (31.1%) the lesions were
      isointense to gray and/or white matter. However, 5 cases (5.4%) showed extremely
      increased signal intensity: two epidermoid cysts; two chordomas; and one brain
      abscess. The entire portion of a tumor was markedly hyperintense in 10 cases
      (10.8%): four malignant lymphomas; four medulloblastomas; one germinoma; and one
      pineoblastoma. A CSF-like hypointense signal was seen in many cystic tumors, and
      cystic or necrotic portions of tumors. A neurosarcoid granulation was the only
      solid lesion showing characteristically a hypointense signal like CSF. The
      combination of markedly hyperintense and hypointense signals was seen generally
      in hemorrhagic tumors. Diffusion-weighted echo-planar MR imaging is useful in the
      differential diagnosis of brain tumors and tumor-like conditions, and suggests
      specific histological diagnosis in some cases.

PMID- 10939506
TI  - A comparison of analogue and digital techniques in upper gastrointestinal
      examinations: absorbed dose and diagnostic quality of the images.
AB  - This study was performed to investigate whether patient exposure and diagnostic
      quality of the image is significantly influenced by the introduction of digital
      image acquisition techniques. Evaluation was performed for three different
      techniques (analogue, analogue fluoro + digital radiography, digital) in
      examination of the upper gastrointestinal tract. The evaluation was done from
      data acquired in three different departments. Patient exposure was recorded as
      KERMA-area product (KAP) and the individual patient readings were normalised to a
      standard size patient. Image quality was assessed using visual grading with a
      reference image. The recorded KAP values were significantly higher (22.3 Gycm2)
      for the fully digital technique compared to the others (analogue 6.8 Gycm2,
      analogue + digital 3.6 Gycm2). This was due mostly to an increased number of
      exposures. The diagnostic quality of the image was, however, also regarded to be
      slightly lower for the technique giving the lowest patient dose with the smallest
      number of exposures (analogue + digital). The digital examination technique, as
      used in this study, thus resulted in significantly higher patient dose without
      any significant gain in diagnostic quality of the image.

PMID- 10939507
TI  - Percutaneous foreign body retrieval through the biliary tract with the Nitinol
      Goose-Neck Snare.

PMID- 10939508
TI  - Supraumbilical skin rash after chemoembolization for hepatocellular carcinoma.

PMID- 10939509
TI  - Intrarenal pseudoaneurysm after percutaneous nephrostolithotomy: endovascular
      treatment with N-butyl-2-cyanoacrylate.

PMID- 10939510
TI  - Embolization of a perforation of a cortical renal artery occurring during
      percutaneous renal angioplasty.

PMID- 10939511
TI  - A ruptured teratoma with malignant transformation.

PMID- 10939512
TI  - Quiz case of the month. A 26-year-old woman presented to her gynecologist with
      dyspareunia.

PMID- 10939513
TI  - Nuclear localisation of the transcription factor Stat5b is associated with ovine
      milk protein gene expression during lactation but not during late pregnancy or
      forced weaning.
AB  - Localisation patterns of the transcription factor Stat5b in the udders from
      pregnant, lactating and involuting ewes were compared with the expression
      patterns of two major milk protein genes alpha-lactalbumin and alphaS1 casein.
      Stat5b was detected in the cytoplasm and nuclei of epithelial cells at all stages
      of mammary gland development. A consistent positive relationship between the
      nuclear localisation of Stat5b in lactating mammary alveolar epithelial cells,
      and the presence of milk protein gene mRNA was apparent during lactation and
      early involution. Conversely, there was little evidence of nuclear localisation
      of Stat5b in non-lactating mammary alveolar epithelial cells during lactation and
      early involution. This supports the observation that during lactation, Stat5b may
      play a role in milk protein gene expression. However, during pregnancy and later
      involution, while Stat5b was observed to be present in mammary epithelial cell
      nuclei and cytoplasm, no relationship between this and the presence of milk
      protein gene mRNA was apparent. This suggests that during late pregnancy and in
      later involution, Stat5b may be involved in processes other than initiation of
      milk protein gene transcription.

PMID- 10939514
TI  - Expression of the HB9 homeobox gene concomitant with proliferation accompanying
      epidermal stratification during development of chick embryonic tarsometatarsal
      skin.
AB  - A homeobox gene, HB9, has been isolated from the tarsometatarsal skin of 13-day
      old chick embryos using a degenerate RT-PCR-based screening method. In situ
      hybridization analysis revealed that, during development of chick embryonic skin,
      the HB9 gene was expressed in epidermal basal cells of the placodes, but not in
      those of interplacodes, and in the dermal cells under the placodes at 9 days
      before addition of an intermediate layer by proliferation of the basal cells in
      the placodes. With the onset of epidermal stratification, the direction of the
      basal cell mitosis changed, with the axis becoming vertical to the epidermal
      surface. Placodes and interplacodes form outer and inner scales, respectively,
      after they have elongated distally (Tanaka S, Kato Y (1983b) J Exp Zool 225: 271
      283). During scale ridge elongation at 12-15 days, HB9 was strongly expressed in
      the epidermis of the outer scale face, where the cell proliferation is more
      active than in the epidermis of the inner scale face; hence, stratification of
      the outer scale face is more prominent than that of the inner scale face. After
      16 days, when mitotic activity in the epidermal basal cells decreases and the
      thickness of the epidermis is maintained at a constant level, the HB9 expression
      decreases with the onset of epidermal keratinization. These results suggest that
      HB9 may be involved in the proliferation of the epidermal basal cells that
      accompanies epidermal stratification.

PMID- 10939515
TI  - Lectin cytochemical characterization of the N- and O-linked oligosaccharides in
      the human rectum.
AB  - The oligosaccharides of the mucus glycoproteins of the human rectum are important
      for the lubricant and protective role suggested for the rectal mucus. Changes in
      oligosaccharide composition are observed in several colon diseases, and some of
      these changes could be used as diagnostic and prognostic indicators. Thus, a
      previous knowledge of the normal mucus glycoproteins is necessary. The aim of the
      present study is the characterization of the oligosaccharides of the goblet cells
      and enterocytes of the human rectum. For this, a battery of 15 lectins, in
      combination with chemical and enzymatic deglycosylation procedures, was used. Our
      results suggest the presence of N-acetylglucosamine (GlcNAc), Man, Glc, N
      acetylneuraminic acid (Neu5Ac)(alpha2-6)- and Neu5Ac(alpha2-3)-linked, N
      acetylgalactosamine (GalNAc) and Gal(beta1-3)GalNAc in the oligosaccharides of
      the goblet cells. Moreover, N-linked oligosaccharides specifically contained
      Gal(beta1-4)GlcNAc, while AAA-positive Fuc was only detected in O-linked
      oligosaccharides. Some of these carbohydrates were only visualized after removal
      of N- or O-linked oligosaccharides, suggesting a high level of approximation
      between the oligosaccharide chains, that render the carbohydrate inaccessible to
      the lectins. Differences in the labelling pattern between the goblet cells of the
      surface epithelium and the upper half of the crypts, and those of the lower half
      of the crypts suggests a maturation process for the goblet cells, which modifies
      the oligosaccharide composition of the secreted glycoproteins, as they ascend
      throughout the crypts. This maturation process includes the incorporation of new
      carbohydrates (GlcNAc), and the masking (Neu5Ac(alpha2-3)-linked) or unmasking
      (Glc and GalNAc) of others.

PMID- 10939516
TI  - Subcellular localization of epidermal growth factor in human submandibular gland.
AB  - Epidermal growth factor in human submandibular gland was localized at the
      subcellular level by means of an immunogold staining method. Labelling was
      observed in serous acini and ducts. In the acini, gold particles were found
      within secretory granules, indicating that the growth factor is released into the
      saliva through granule exocytosis. In the ductal system, the most intense
      reactivity was revealed in the principal cells of striated ducts. In these cells,
      an abundant population of small cytoplasmic vesicles was specifically stained.
      Immunoreactive vesicles were found both apically and basally, suggesting that
      ductal cells can release their products not only into the saliva but also into
      the interstitium.

PMID- 10939517
TI  - Colocalization of numerous immunoreactivities in endocrine cells of the chicken
      proventriculus at hatching.
AB  - The colocalization of regulatory peptide immunoreactivities in endocrine cells of
      the chicken proventriculus at hatching has been investigated using the avidin
      biotin technique in serial sections and double immunofluorescence in the same
      section for light microscopy, and double immunogold staining for electron
      microscopy. In addition to the eight immunoreactivities previously described in
      this organ, cells immunoreactive for peptide histidine isoleucine (PHI), peptide
      gene product 9.5 (PGP), and the amidating enzyme, peptidylglycine alpha-amidating
      monooxygenase (PAM) were observed. All the cells immunoreactive to glucagon were
      also immunostained by the PHI antiserum. In addition, all the glucagon-like
      peptide 1, avian pancreatic polypeptide, and some of the neurotensin-like cells
      costored also glucagon- and PHI-immunoreactive substances. PGP- and PAM
      immunoreactivities were also found in the glucagon-positive cells. A small
      proportion of the somatostatin-containing cells were positive for PHI but not for
      other regulatory peptides. These results could suggest either the existence of a
      very complex regulatory system or that the endocrine system of the newborn
      chickens is not yet fully developed.

PMID- 10939518
TI  - Skeletal muscle fibres show NADPH diaphorase activity associated with
      mitochondria, the sarcoplasmic reticulum and the NOS-1-containing sarcolemma.
AB  - The subcellular appearance of NADPH diaphorase activity in different rat skeletal
      muscles has been analyzed. Both a sarcolemma-associated as well as a non
      sarcolemma-associated NADPH diaphorase-dependent generation of formazan was
      observed. The sarcolemma-associated NADPH diaphorase staining appeared regularly
      in two manifestations: one observed in longitudinal sections as dotted costameres
      at the cell surface which accordingly appeared in transversal sections as rings
      surrounding the myofibre surface. At this site, nitric oxide synthase (NOS)-1 was
      located. The second sarcolemma-associated site of NADPH diaphorase staining was
      found as bundles of longitudinal-orientated stripes of hitherto unidentified
      origin. The non-sarcolemma-associated production of formazan was likewise
      manifested at two sites: the first was found regularly in longitudinal sections
      as intense sarcomere-like striations occurring parallel to the I-bands and
      indicating mitochondria. The second non-sarcolemma-associated NADPH diaphorase
      staining was realized as fine longitudinal filaments of variable occurrence
      connecting the mitochondria and presumably belonging to the sarcoplasmic
      reticulum. Attempts to identify single NADPH diaphorase(s) existing in skeletal
      muscles by incubation with specific inhibitors failed but showed the presence of
      two different subpopulations of NADPH diaphorases in myofibres: a urea-resistant
      fraction in the sarcolemma region containing NOS-1 and a non-sarcolemma
      associated, urea-sensitive fraction depleted of NOS-1.

PMID- 10939519
TI  - Calcium-dependent ATPase unlike ecto-ATPase is located primarily on the luminal
      surface of brain endothelial cells.
AB  - Numerous cytochemical studies have reported that calcium-activated adenosine
      triphosphatase (Ca2+-ATPase) is localized on the abluminal plasma membrane of
      mature brain endothelial cells. Since the effects of fixation and co-localization
      of ecto-ATPase have never been properly addressed, we investigated the influence
      of these parameters on Ca2+-ATPase localization in rat cerebral microvessel
      endothelium. Formaldehyde at 2% resulted in only abluminal staining while both
      luminal and abluminal surfaces were equally stained following 4% formaldehyde.
      Fixation with 2% formaldehyde plus 0.25% glutaraldehyde revealed more abluminal
      staining than luminal while 2% formaldehyde plus 0.5% glutaraldehyde produced
      vessels with staining similar to 4% and 2% formaldehyde plus 0.25%
      glutaraldehyde. The abluminal reaction appeared unaltered when ATP was replaced
      by GTP, CTP, UTP, ADP or when Ca2+ was replaced by Mg2+ or Mn2+ or p
      chloromercuribenzoate included as inhibitor. But the luminal reaction was
      diminished. Contrary to previous reports, our results showed that Ca2+-specific
      ATPase is located more on the luminal surface while the abluminal reaction is
      primarily due to ecto-ATPase. The strong Ca2+-specific-ATPase luminal
      localization explains the stable Ca2+ gradient between blood and brain, and is
      not necessarily indicative of immature or pathological vessels as interpreted in
      the past.

PMID- 10939521
TI  - Isolation of replicational cue elements from a library of bent DNAs of
      Aspergillus oryzae.
AB  - Two fragments that could function as replicational cue elements were isolated
      from a genomic DNA digest of Aspergillus oryzae on the basis of abnormal behavior
      in polyacrylamide gel electrophoresis. The vector used in this study contained a
      scaffold-associated region of the Drosophila melanogaster ftz gene to provide
      nuclear retention. Neither fragment contained a yeast ARS consensus sequence or
      an eukaryotic topoisomerase II binding sequence. One of the fragments showed
      sequence homology with the mitochondrial replication origin of Candida utilis and
      a portion of mitochondrial DNA of Aspergillus nidulans. This plasmid carrying the
      cue fragment could also replicate in HeLa and NIH3T3 cells.

PMID- 10939520
TI  - Hydrogen peroxide-induced apoptosis in human hepatoma cells is mediated by
      CD95(APO-1/Fas) receptor/ligand system and may involve activation of wild-type
      p53.
AB  - Reactive oxygen species (ROS) play an important role in cell death induced by
      many different stimuli. Direct exposure of human hepatoma cell line SMMC-7221 to
      hydrogen peroxide (H2O2) can induce apoptosis characterized by morphological
      evidence and fragmentation of DNA assayed by terminal deoxynucleotidyl
      transferase assay (TUNEL assay). Analysis of flow cytometry indicated that H2O2
      can decrease the level of CD95(APO-1/Fas), and it is confirmed that H2O2 can also
      activate the differential expression of some specific gene such as p53 by means
      of RT-PCR technique. The results indicated that CD95 signal transduction system
      may be involved in the H2O2-induced apoptosis, and can regulate some specific
      genes associated with apoptosis in transcription and translation levels such as
      p53.

PMID- 10939522
TI  - The efficiency of different IRESs (internal ribosomes entry site) in
      monocistronic mRNAS.
AB  - The IRES from poliovirus and from encephalomyocarditis virus (EMCV) added between
      the cap and the AUG initiator codon were strong inhibitors of chloramphenicol
      acetyltransferase gene expression in three different cell types. The poliovirus
      IRES also inhibited bGH (bovine growth hormone) cDNA expression in the HC11
      mammary cell line when added between the rabbit whey acidic gene promoter and the
      cDNA whereas the HTLV-1 IRES showed a stimulatory effect in the same situation.
      RNA stem loops were added before HTLV-1 (SUR) and the BiP (Immunoglobulin heavy
      chain Binding Protein) IRESs followed by the firefly luciferase gene under the
      control of Rous sarcoma virus (RSV) promoter. The RNA loops abolished the
      expression of the reporter gene almost completely. These data suggest that the
      different IRESs may favour or inhibit translation of monocistronic mRNA.

PMID- 10939523
TI  - Characterization of the cys gene locus from Allochromatium vinosum indicates an
      unusual sulfate assimilation pathway.
AB  - Homologues of the genes cysB, cysI, cysH, cysD, cysN, and selD were identified in
      the genome of the phototrophic purple sulfur bacterium Allochromatium vinosum
      (formerly Chromatium vinosum). On the basis of amino acid comparisons these genes
      encode a ferredoxin-dependent siroheme-sulfite reductase (CysI), a plant-type
      assimilatory APS reductase without thioredoxin domain (CysH), the two different
      subunits of heterodimeric ATP sulfurylase (CysDN), a transcriptional regulator
      (CysB) and a selenophosphate synthase (SelD). cysIHDN appear to form an operon
      and are preceded by cysB which is transcribed in the opposite direction. SelD is
      situated downstream of cysN and transcribed divergently to cysIHDN. The lack of a
      gene for APS kinase and presence of a gene for an assimilatory APS reductase
      implies that assimilatory sulfate reduction in A. vinosum proceeds along the
      pathway suggested for higher plants without intermediary formation of PAPS. Two
      completely separate pathways involving specialized enzymes are used for
      assimilatory sulfate reduction and dissimilatory sulfur oxidation in A. vinosum.
      The presence of cysB indicates that the genes for assimilatory sulfate reduction
      are expressed only in the absence of reduced sulfur compounds.

PMID- 10939524
TI  - Further characterization of the actin-related protein Act3p/Arp4 of S. cerevisiae
      through mutational analysis.
AB  - In the course of functional analysis of the yeast ARP4 (ACT3) gene, we further
      characterized the role of its protein product Arp4p in the cell. We report that
      although it is localized in the nucleus, Arp4p performs its function
      independently of binding to DNA directly. The roles of the core actin structure
      (the ATP-binding pocket) and a putative Nuclear Localization Signal (NLS) of
      Arp4p were tested by targeted mutagenesis. The results suggest that under normal
      conditions, the ATPase activity and the NLS are dispensable for the essential
      function of this protein in the cell. Furthermore, the use of reporter genes
      confirmed that Arp4p could be involved in some general mechanism of
      transcriptional regulation.

PMID- 10939525
TI  - Cloning and sequence analysis of lily and tobacco guanylate kinases.
AB  - Guanylate kinase is an essential enzyme in the nucleotide biosynthetic pathway,
      catalyzing the reversible transfer of the terminal phosphoryl group of ATP to GMP
      or dGMP. This enzyme has been well studied from several organisms and many
      structural and functional details have been characterized. Animal GMP kinases
      have also been implicated in signal transduction pathways. However, the
      corresponding role by plant derived GMP kinases remains to be elucidated. Full
      length cDNA clones encoding enzymatically active guanylate kinases were isolated
      from cDNA libraries of lily and tobacco. Lily cDNA is predicted to encode a 392
      amino acid protein with a molecular mass of 43.1 kDa and carries amino- and
      carboxy- terminal extensions of the guanylate kinase (GK)-like domain. But
      tobacco cDNA is predicted to encode a smaller protein of 297-amino acids with a
      molecular mass of 32.7 kDa. The amino acid residues known to participate in the
      catalytic activity of functionally characterized GMP kinases, are also conserved
      in GK domains of LGK-1 and NGK-1. The GK domains of NGK-1, LGK-1 and previously
      characterized AGK-1 from Arabidopsis exhibit 74-84% identity, whereas their N-
      and C-terminal domains are more divergent with amino acid conservation in the
      order of 48-55%. Phylogenetic analysis on the deduced amino acid sequences
      reveals that NGK-1 and LGK-1 form one distinct subgroup along with AGK-1 and AGK
      2 homologues from Arabidopsis. Isolation of GMP kinases from diverse plant
      species like lily and tobacco adds a new dimension in understanding their role in
      cell signaling pathways that are associated with plant growth and development.

PMID- 10939526
TI  - Specific induction of Z-DNA conformation by a nuclear localization signal peptide
      of lupin glutaminyl tRNA synthetase.
AB  - Recently we have sequenced cDNA of plant glutaminyl-tRNA synthetase (GlnRS) from
      Lupinus luteus. At the N terminal part the protein contains a lysine rich
      polypeptide (KPKKKKEK), which is identical to a nuclear localization signal
      (NLS). In this paper we showed that two synthetic peptides (20 and 8 amino acids
      long), which were derived from lupin GlnRS containing the NLS sequence interact
      with DNA, but one of them (8aa long) changing its conformation from the B to the
      Z form. This observation clearly suggests that the presence of the NLS
      polypeptide in a leader sequence of GlnRS is required not only for protein
      transport into nucleus but also for regulation of a gene expression. This is the
      first report suggesting a role of the NLS signal peptide in structural changes of
      DNA.

PMID- 10939527
TI  - Homomeric interaction of the mouse Rad52 protein.
AB  - The Rad52 protein plays a crucial role in repairing DNA damage and homologous
      recombination, possibly by virtue of its ability to catalyze annealing of single
      stranded DNA. In agreement with recent genetic data, we here present results
      based on the two-hybrid system, demonstrating that mouse Rad52p is able to form
      homomeric complexes. A small domain necessary and sufficient for the self
      interaction is located in the conserved N-terminus of the protein. These data
      contribute to the important insights into the architecture of the multi-protein
      complex involved in recombinational DNA repair.

PMID- 10939528
TI  - "Multi-effect" macrolides.

PMID- 10939529
TI  - Renal involvement in Fabry's disease.

PMID- 10939530
TI  - Antineutrophil cytoplasmic antibody (ANCA)-associated crescentic
      glomerulonephritis.

PMID- 10939531
TI  - Interferon therapy in Behcet's disease.

PMID- 10939532
TI  - Primary focal segmental glomerulosclerosis: clinical course, predictors of renal
      outcome and treatment.
AB  - Primary focal segmental glomerulosclerosis (FSGS) is the representative of
      refractory nephrotic syndrome in both adults and children. We review the clinical
      course and predictors of renal outcome in adult FSGS. Patients resistant to
      treatment frequently develop end-stage renal disease (ESRD), whereas patients
      achieving a remission show an excellent outcome. The renal survival rate in
      Japanese patients is 68.7% in 10 years and 31.4% in 20 years, indicating a better
      prognosis compared with the previous studies. When clinical and histological
      features at presentation have been evaluated by multivariate analysis, serum
      creatinine concentrations (>1.5 mg/dl) and the presence of tubulo-interstitial
      lesions (>20%) are significant positive predictors of progression to ESRD. We
      also discuss treatment for adult FSGS, with emphasis on intensive and prolonged
      therapy.

PMID- 10939533
TI  - Evaluation of global and regional left ventricular function obtained by
      quantitative gated SPECT using 99mTc-tetrofosmin for left ventricular
      dysfunction.
AB  - OBJECTIVE: The quantitative gated SPECT (QGS) software is able to calculate LV
      volumes and visualize LV wall motion and perfusion throughout the cardiac cycle
      using an automatic edge detection algorithm of the left ventricle. We evaluated
      the reliability of global and regional LV function assessment derived from QGS by
      comparing it with the results from left ventriculo-cineangiography (LVG).
      PATIENTS: In 20 patients with left ventricular dysfunction who underwent ECG
      gated 99mTc-tetrofosmin SPECT, the end-diastolic volume (EDV), end-systolic
      volume (ESV) and ejection fraction (LVEF) were calculated. The QGS-assessed
      regional wall motion was determined using the cinematic display. RESULTS: QGS
      derived EDV, ESV and LVEF correlated well with those by LVG (p<0.001 for each).
      There was a good correlation between wall motion score (WMS) derived from the QGS
      and the LVG (r=0.40, p<0.05). In some patients with extensive myocardial
      infarction, there was a discrepancy in the regional wall motion results between
      QGS and LVG. CONCLUSIONS: The ECG-gated SPECT using QGS is useful to evaluate
      global and regional LV functions in left ventricular dysfunction.

PMID- 10939534
TI  - Transcriptional regulation of IL-5 gene by nontransformed human T cells through
      the proximal promoter element.
AB  - OBJECTIVE: IL-5 is strongly involved in the eosinophilic inflammation in
      bronchial asthma and atopic dermatitis. We have previously reported that IL-5
      synthesis in atopic and nonatopic asthmatics is significantly enhanced compared
      to control subjects. T cell IL-5 synthesis is regulated through several
      transcriptional elements, one of which is the proximal human IL-5 promoter (-62
      to -46). The present study was undertaken to delineate the transcriptional
      regulation through this element using nontransformed human T cells. METHODS: Con
      A blast lymphocytes which tolerate electroporation were derived from peripheral
      blood lymphocytes. Luciferase reporter analysis and gel shift analysis were
      performed. RESULTS: The proximal promoter element is the overlapping binding site
      for the constitutive binding factor, Oct-1, and the inducible one, AP-1. The
      transcriptional induction was ascribed to the inducible binding, while the
      constitutive binding was rather inhibitory. A mutant element which lost the
      constitutive binding but retained the inducible binding exerted 3 times more
      transcriptional activity compared to the wild type element. In contrast, another
      mutant element which lost the inducible binding and retained the constitutive
      binding exhibited no transcriptional induction. Gel shift analysis clarified that
      the inducible binding was more prominent and the constitutive binding was less in
      IL-5-producing T cells derived from asthma patients compared to IL-5-nonproducing
      cells derived from control subjects. CONCLUSIONS: The ratio of the
      inducible/constitutive binding to the proximal promoter element may determine the
      capacity of human Th cells to transcribe IL-5 gene, and its regulation may
      control eosinophilic inflammation.

PMID- 10939535
TI  - Midgut malrotation in adulthood.
AB  - A 29-year-old man was admitted to our hospital with a history of recurrent right
      upper quadrant abdominal pain and vomiting. These symptoms appeared
      intermittently for 7 years. Various examinations revealed a diagnosis of midgut
      malrotation. Laparotomy was performed and revealed reverse rotation of the
      duodenum with paraduodenal hernia and a normal rotating colon. This case suggests
      that recurrent abdominal complaints in an adult should arouse suspicion of midgut
      malrotation.

PMID- 10939536
TI  - A fatal case of fulminant myocarditis with human herpesvirus-6 infection.
AB  - We report a case of fulminant myocarditis after steroid pulse therapy for acute
      hepatitis. Serological studies demonstrated a four-fold increase in the
      antibodies against human herpesvirus-6 (HHV-6) IgG, and a PCR showed the
      existence of HHV-6 virus DNA. HHV-6 virus DNA was also isolated from the liver
      and the heart. We believe that exacerbation of fulminant myocarditis was probably
      associated with the reactivation of HHV-6 due to the immunosuppressive state of
      the host.

PMID- 10939537
TI  - Hypertrophic cardiomyopathy complicated with cardiac amyloidosis.
AB  - The echocardiographic findings of hypertrophic cardiomyopathy (HCM) are very
      similar to those of cardiac amyloidosis. A 76-year-old Japanese man was admitted
      for treatment of early stage gastric cancer in July 1996. His electrocardiogram
      indicated left ventricular hypertrophy and echocardiography showed left
      ventricular hypertrophy with asymmetric septal hypertrophy. He was re-admitted
      complaining of dyspnea on effort and pretibial edema in October 1998. The
      amplitude of QRS complex on electrocardiogram was decreased. Echocardiogram
      showed left ventricular wall thickening with granular sparkling. He was diagnosed
      as HCM with cardiac amyloidosis.

PMID- 10939538
TI  - A patient of hypogonadotropic hypogonadism accompanied by growth hormone
      deficiency and decreased bone mineral density who attained normal growth.
AB  - We present here a rare case of hypopituitarism accompanied by growth hormone (GH)
      deficiency and hypogonadotropic hypogonadism, in which the patient attained
      normal height but was of eunuchoid appearance. A 23-year-old man who had not
      reached puberty was referred to Saitama Medical School for hormonal evaluation.
      Basal hormonal data and hormone-stimulating tests revealed impaired secretion of
      GH, gonadotropins and adrenocorticotropic hormone (ACTH). Serum levels of
      testosterone, estrone, estradiol and estriol were all below the detectable
      ranges. The patient's plasma ACTH responded to corticotropin releasing hormone,
      but not to insulin-induced hypoglycemia. Serum GH showed a minimal response to GH
      releasing hormone, but was unresponsive to insulin-induced hypoglycemia. Serum
      luteinizing hormone and follicle stimulating hormone did not respond to
      luteinizing hormone-releasing hormone. The results were compatible with a
      diagnosis of hypothalamic hypopituitarism. Magnetic resonance images of the brain
      showed a small anterior pituitary, an ectopic posterior lobe and transection of
      the pituitary stalk. Although the patient showed signs of hypopituitarism, he
      finally attained normal height, possibly because of failed epiphyseal maturation.
      His bone mineral density was markedly reduced to 0.647 g/cm2 in the lumbar spine;
      this level was 61.7% of the average level of healthy young males. Our findings
      were compatible with a recently advocated view that estrogen is important in
      promoting epiphyseal fusion and in determining bone density in males as well as
      females.

PMID- 10939539
TI  - Atypical Fabry's disease presenting with cholesterol crystal embolization.
AB  - We describe a 65-year-old man who presented with pulmonary hemorrhage and
      progressive renal insufficiency three months after resection surgery for an
      abdominal aortic aneurysm. Intensive treatment with corticosteroids and
      hemodialysis were not effective, and the patient died. Postmortem examination of
      the kidneys revealed widespread cholesterol clefts within the renal arterioles
      and a number of lamellar inclusion bodies were observed by electron microscopy.
      The diagnosis of Fabry's disease was made by the absence of plasma alpha
      galactosidase A activity. This was a very rare case of subclinical Fabry's
      disease coexistent with cholesterol crystal embolization, mimicking pulmonary
      renal syndrome.

PMID- 10939540
TI  - Crescentic glomerulonephritis with positive antineutrophil cytoplasmic
      autoantibody specific for myeloperoxidase associated with autoimmune hemolytic
      anemia and thrombocytopenic purpura.
AB  - A 41-year-old woman was admitted to the hospital with severe uremia, hemolytic
      anemia, and thrombocytopenic purpura. Emergency hemodialysis with plasmapheresis
      was started in view of consideration of hemolytic uremic syndrome (HUS), which
      resulted in improvement of renal function and platelet count. Positive
      antineutrophil cytoplasmic autoantibody specific for myeloperoxidase (MPO-ANCA)
      suggested crescentic glomerulonephritis, which was pathologically evidenced by
      renal biopsy. The diagnosis of MPO-ANCA associated crescentic glomerulonephritis
      with autoimmune hemolytic anemia (AIHA) and thrombocytopenic purpura were
      confirmed. Three courses of steroid pulse therapy with heparin were successfully
      performed, followed by oral prednisolone and warfarin. Such a case has not been
      previously reported to our knowledge.

PMID- 10939541
TI  - Synchronous primary adenocarcinoma of the lung and leiomyosarcoma of the small
      intestine.
AB  - The occurrence of synchronous epithelial cancer of the lung and leiomyosarcoma of
      the small intestine is rare. We report here the case of a 62-year-old man with
      adenocarcinoma of the lung in clinical stage IIIB (T4N0M0). After two courses of
      chemotherapy (cisplatin, 80 mg/m2 and mitomycin C, 8 mg/m2) the patient developed
      symptoms of a small bowel obstruction. Palliative surgical resection was
      performed and a leiomyosarcoma of the small intestine was found and defined by an
      immunohistological study. The resection ameliorated the patient's symptoms. The
      patient died of disseminated adenocarcinoma 26 months following chemotherapy.

PMID- 10939542
TI  - The pitfall in evaluating several serological markers of Pneumocystis carinii
      pneumonia in a neutropenic patient.
AB  - We compared the significance of several serum markers to evaluate the activity of
      Pneumocystis carinii pneumonia (PCP) in an immunocompromised patient. We
      successively measured KL-6, an amino-terminal propeptide of Type III procollagen
      (PIIINP), and the cytokeratin 19 fragment (CK19) in the sera of a patient with
      PCP. Interestingly, PIIINP, KL-6, and CK19 levels in the sera did not increase at
      the time of onset of PCP during a neutropenic phase. Instead, they markedly
      increased after the recovery of WBC counts. This case suggests that values of
      PIIINP, KL-6, and CK19 used for monitoring the activity of PCP might be
      underestimated in neutropenic patients.

PMID- 10939543
TI  - A patient with cyclic neutropenia complicated by severe persistent neutropenia
      successfully delivered a healthy baby.
AB  - We describe a 24-year-old pregnant woman complicated by cyclic neutropenia (CN),
      who was successfully treated with granulocyte-colony stimulating factor (G-CSF).
      Her white blood cell (WBC) and neutrophil count fluctuated from 2,600 to
      4,600/microl, and 26 to 2,530/microl, respectively. The peak neutrophil count
      gradually decreased as pregnancy advanced, resulting in the disappearance of its
      cyclicity. At 39 weeks of pregnancy when the neutrophil count became 84/microl,
      the patient was started on G-CSF and her neutrophil count increased to
      1,550/microl on the fourth day after delivery. She delivered a healthy baby
      without any complications at 39 weeks of pregnancy.

PMID- 10939544
TI  - Beneficial effects of interferon-alpha in a case with Behcet's disease.
AB  - At the age of 20 years, a Japanese man with recurrent oral aphthae, genital
      ulcers, folliculitis, erythema nodosum, episodic arthritis and epididymitis was
      diagnosed as having Behcet's disease (BD) in 1966. He has had active ocular
      manifestations of BD since 1990. These symptoms recurred and never abated for a
      long period of time. A right renal cell carcinoma developed and he underwent
      right nephrectomy in April 1996. Treatment with interferon-alpha was started from
      June 1996 as supplemental chemotherapy. No active phase developed during
      administration of IFN-alpha. We suggest that IFN-alpha may play a role as an
      immunomodulatory agent in BD.

PMID- 10939545
TI  - Familial cases of severe measles pneumonia.
AB  - We report two cases of severe measles pneumonia. Patient 1, a 17-year-old boy who
      contracted measles in the acute phase of infectious mononucleosis caused by
      Epstein-Barr virus (EBV), transmitted the disease to patient 2, his father. Both
      patients presented severe pneumonia with bilateral diffuse micronodular shadows.
      Diagnoses were established in both patients by antibody titers for measles and
      reverse transcriptase-polymerase chain reaction (RT-PCR) of blood and throat
      swab. Multinucleated giant cells with intranuclear inclusion bodies were revealed
      in the transbronchial lung biopsy (TBLB) specimen of patient 2. Both patients
      recovered with pulse steroid therapy.

PMID- 10939546
TI  - Hereditary hemorrhagic telangiectasia (HHT) in Akita Prefecture, Japan.

PMID- 10939547
TI  - Streptococcus bovis discitis and possible endocarditis.

PMID- 10939548
TI  - The need for leadership in a changing health care landscape.

PMID- 10939549
TI  - Can you help us build our town?

PMID- 10939551
TI  - Cost-minimization analysis of phenytoin and fosphenytoin in the emergency
      department.
AB  - STUDY OBJECTIVE: To determine the value of fosphenytoin compared with phenytoin
      for treating patients admitted to an emergency department following a seizure.
      DESIGN: Cost-minimization analysis performed from a hospital perspective.
      SETTING: Hospital emergency department. PATIENTS: Two hundred fifty-six patients
      participating in a comparative clinical trial. INTERVENTION: Estimation of
      adverse event rates and resource use. MEASUREMENTS AND MAIN RESULTS: In our base
      case, phenytoin was the preferred option, with an expected total treatment cost
      of $5.39 compared with $110.14 for fosphenytoin. One-way sensitivity analyses
      showed that the frequency and cost of treating purple glove syndrome (PGS)
      possibly could affect the decision. Monte Carlo simulation showed phenytoin to be
      the preferred option 97.3% of the time. CONCLUSION: When variable costs of care
      are used to calculate the value of phenytoin compared with fosphenytoin in the
      emergency department, phenytoin is preferred. The decision to administer
      phenytoin was very robust and changed only when both the frequency and cost of
      PGS was high.

PMID- 10939550
TI  - Variability in activity of hepatic CYP3A4 in patients infected with HIV.
AB  - STUDY OBJECTIVES: To evaluate hepatic cytochrome P450 (CYP) 3A4 activity in
      patients infected with the human immunodeficiency virus (HIV) using the
      erythromycin breath test (ERMBT), and to examine the relationship of the ERMBT to
      plasma concentrations of indinavir and nelfinavir. DESIGN: Prospective
      observational study. SETTING: University infectious diseases clinic. SUBJECTS:
      Thirty-nine HIV-positive patients and 47 healthy controls. INTERVENTION: After
      the ERMBT in patients and controls, 25 patients received indinavir or nelfinavir.
      MEASUREMENTS AND MAIN RESULTS: Compared with controls, ERMBT variability was
      significantly greater in HIV-positive patients, including a subset of 19 patients
      receiving no concurrent drugs reported to alter CYP3A4 activity. Correlation
      between the ERMBT and first-dose plasma indinavir concentrations nearly reached
      statistical significance (p=0.07). CONCLUSION: Variability in hepatic activity of
      CYP3A4 in HIV-positive patients may be greater than in controls and may explain
      some between-subject variability in plasma concentrations of indinavir. However,
      clearance mechanisms for protease inhibitors are complex, and if it is important
      to assess systemic exposure, the ERMBT is not a substitute for direct measurement
      of plasma concentrations.

PMID- 10939552
TI  - Semen and serum pharmacokinetics of zidovudine and zidovudine-glucuronide in men
      with HIV-1 infection.
AB  - STUDY OBJECTIVE: To characterize the concentration-time profiles of zidovudine
      and zidovudine-glucuronide in semen and serum of men infected with the human
      immunodeficiency-1 virus (HIV-1). DESIGN: Open-label observational study.
      SETTING: University-affiliated teaching hospital and research center. PATIENTS:
      Four asymptomatic HIV-1-infected men. INTERVENTIONS: Zidovudine administration
      was followed by an 8-hour intensive pharmacokinetic study on day 1. Over the next
      8 days, a dose administration and timed single-sample strategy was employed to
      determine serum and semen concentration time profiles simultaneously.
      MEASUREMENTS AND MAIN RESULTS: Zidovudine and zidovudine-glucuronide
      concentrations were uniformly higher in semen than in serum except at 1 hour
      after the dose. The median area under the curve ratio (semen AUC0-48:serum AUC0
      infinity) was 3.31 for zidovudine and 15.04 for zidovudine-glucuronide.
      CONCLUSION: Zidovudine and zidovudine-glucuronide reach high levels in seminal
      plasma relative to serum. The virologic, pharmacodynamic, and public health
      implications of distribution to this compartment require further study.

PMID- 10939553
TI  - Evaluation of warfarin initiation regimens in elderly inpatients.
AB  - STUDY OBJECTIVE: To compare initial warfarin doses of 5 mg or below and doses
      above 5 mg in hospitalized elderly. DESIGN: Retrospective review of charts
      identified from computerized pharmacy records. SETTING: County teaching hospital.
      PATIENTS: Inpatients aged 65 years or older receiving at least three warfarin
      doses. INTERVENTION: We measured the time to first international normalized ratio
      (INR) of 2.0 or greater, bleeding complications, number of warfarin doses held,
      and vitamin K use. MEASUREMENTS AND MAIN RESULTS: The average initial low dose
      (33 patients) was 4.8 +/- 0.8 mg and the average initial high dose (40 patients)
      was 9.0 +/-1.2 mg. The mean time to first INR of 2.0 or greater was similar, 3.4
      and 3.0 days, respectively (p=0.38). The low-dose group had fewer bleeds (7 vs
      13, p=0.28) and doses held (11 vs 18 patients, p=0.27, 30 vs 50 doses). Four
      patients in each group received vitamin K (p=0.8). Forty-four percent of patients
      with an INR of 4 or above and 48% of patients who had a dose held were on a long
      term drug or had a new drug added that could cause a major drug interaction with
      warfarin. CONCLUSION: In this pilot study, hospitalized elderly who received a
      low versus high initial dose of warfarin achieved therapeutic INRs in a similar
      time and had lower but not significantly different safety outcomes.

PMID- 10939554
TI  - A new ciprofloxacin stepdown program in the treatment of high-risk febrile
      neutropenia: a clinical and economic analysis.
AB  - STUDY OBJECTIVE: To determine treatment outcomes and economic impact of a
      ciprofloxacin stepdown program for high-risk febrile neutropenic adults from the
      hospital's perspective. DESIGN: Unblinded, two-phase, single-center study.
      SETTING: Adult leukemia and stem cell transplant unit. PATIENTS: High-risk adults
      with febrile neutropenia. INTERVENTION: Two conditions were analyzed: a
      multidisciplinary ciprofloxacin stepdown program involving a reduction in
      parenteral ciprofloxacin dose from 400 to 200 mg (i.v.-i.v.) and conversion to
      oral ciprofloxacin (i.v.-p.o.) when criteria were met; and no i.v.-i.v. stepdown
      program. MEASUREMENTS AND MAIN RESULTS: Forty-six sequential treatment courses
      were compared with 42 treatment course from 6-month periods in preintervention
      (P1) and postintervention (P2) phases. Assessed parameters were clinical and
      microbiologic outcomes, adverse drug reactions (ADRs), and direct medical
      resource use and costs (1998 $Canadian) for the episode of febrile neutropenia. A
      decision analytic model was used to map probabilities and costs and to conduct
      sensitivity analyses. To supplement standard statistical testing, 1,000 bootstrap
      samples were created, and the mean cost difference was calculated between phases
      for each sample. Patient demographics, percentage i.v.-p.o. stepdown, and
      duration of therapy were similar between phases. Clinical success (83% P1, 81%
      P2), microbiologic eradication (15% P1, 24% P2), and possible ADRs (6% P1, 9% P2)
      did not differ. Intravenous-to-intravenous dose stepdown occurred in 33% of P2
      and no P1 treatment courses (p<0.001). Resource use and costs were similar
      between phases, although a reduction was seen in the drug's mean total cost/day
      ($58 P1, $52 P2, p=0.04). There was also a trend toward a decrease in mean total
      treatment costs ($4,843 P1, $3,493 P2, p=0.08). In 1,000 bootstrap samples, 99.8%
      showed a cost advantage for P2. The model was robust to sensitivity analyses.
      CONCLUSION: This intervention influenced administration of ciprofloxacin without
      apparent compromise of patient outcomes and resulted in a reduction in total
      costs of treating febrile neutropenia.

PMID- 10939555
TI  - The relationship between drug therapy noncompliance and patient characteristics,
      health-related quality of life, and health care costs.
AB  - The objectives of this study were to determine the relationship between drug
      therapy compliance and risk of hospitalization and economic outcomes, and to
      identify potential indicators of compliance. We used computerized prescription
      records from 1,054 patients at high risk for drug-related problems. We calculated
      a compliance ratio for a 12-month period and correlated it with health care use,
      demographic variables, drug-related variables, and scores for health-related
      quality of life. Univariate results suggested that increased age (p=0.05), high
      number of chronic conditions (p<0.001), and high number of concurrent drugs
      (p<0.001) were positively correlated with compliance. That is, increased values
      for these variables were associated with better compliance. Using logistic
      regression, the odds of being noncompliant was 0.665 as the number of chronic
      conditions increased. Compliance was not a predictor of concurrent or future
      hospitalizations or mortality, nor was it a significant predictor of health care
      costs.

PMID- 10939556
TI  - Cost-effectiveness of sevelamer versus calcium carbonate plus atorvastatin to
      reduce LDL in patients with chronic renal insufficiency with dyslipidemia and
      hyperphosphatemia.
AB  - We conducted a cost-effectiveness analysis to compare costs and clinical outcomes
      of sevelamer versus calcium carbonate plus atorvastatin for treatment of
      dyslipidemia in patients with chronic renal insufficiency. The model was from the
      third-party payer perspective. Efficacy and adverse event rates for each regimen
      were obtained from published clinical trials. Drug costs were based on average
      wholesale prices; monitoring costs were based on Medicare reimbursement rates.
      Our model suggests that the combination of calcium carbonate plus atorvastatin is
      substantially more cost-effective than sevelamer in reducing low-density
      lipoprotein (LDL) in these patients. One-way sensitivity analyses were performed
      to assess if 25% and 50% price reductions in sevelamer affected overall cost
      effectiveness results. A 50% sevelamer price reduction was less expensive than
      combination therapy but remained less cost-effective. A two-way sensitivity
      analysis on the probability that a patient achieves the goal of a 35% LDL
      reduction resulted in calcium carbonate plus atorvastatin remaining more cost
      effective. Further cost-effectiveness studies are necessary to corroborate our
      data.

PMID- 10939558
TI  - Physician prescribing of anorexigenics for weight loss in Salt Lake County, Utah.
AB  - The objective of this survey of primary care physicians in Salt Lake County,
      Utah, was to determine how many of these providers were prescribing anorexigenics
      (antiobesity drugs) and to evaluate their knowledge of side effects and drug
      interactions. A confidential survey was sent to 377 family practice, internal
      medicine, and obstetrics-gynecology physicians, of whom 236 (62.5%) responded. Of
      those who answered the survey completely, 146 (65.2%) prescribed anorexigenics to
      5,107 patients. Family practice physicians, male physicians less than 40 years
      old, and internal medicine physicians less than 40 years old prescribed
      anorexigenics more frequently than their counterparts. Female physicians (vs
      male) and female family practice physicians (vs male family practice physicians)
      reported a higher proportion of psychiatric comorbidity among patients for whom
      they prescribed the drugs. Respondents had limited knowledge of side effects and
      drug interactions of anorexigenics. Better understanding of physicians'
      prescribing patterns of these agents is relevant for current and future optimal
      treatment of obesity.

PMID- 10939557
TI  - Prevalence and patterns of alternative medication use in a university hospital
      outpatient clinic serving rheumatology and geriatric patients.
AB  - A random sample of 176 patients seen at least once during 1997 in a University
      hospital outpatient clinic serving rheumatology and geriatric patients were
      surveyed in a telephone interview to determine the prevalence of, and reasons for
      taking, alternative medications. Interviews were conducted from November 1997
      March 1998. The survey elicited information about patients' ability to provide
      self-care, demographics, work status, satisfaction with current disease
      management, types of alternative medications taken, sources of information about
      the products, where they obtained the products, and reasons for taking the
      products. Patients also were questioned as to their knowledge of safety of these
      products. Statistical comparisons were determined between patients who used
      alternative agents and those who did not. Prevalence of use was 66%. Most
      patients thought that the agents were safe and took them because they believed
      they have "added benefits."

PMID- 10939559
TI  - Evaluation of a pharmacy-based surveillance program for heparin-induced
      thrombocytopenia.
AB  - We instituted a pharmacy-based surveillance and intervention program for heparin
      induced thrombocytopenia (HIT). Surveillance occurred between August 1996 and
      July 1999. Platelet counts were monitored by pharmacists in patients receiving
      heparin 10,000 U/day or more. For patients with declining platelet counts,
      serology was ordered and clinicians were advised as appropriate. Outcomes of HIT
      in the surveillance group were compared with historical cases. During
      surveillance of 8,672 heparin courses, the incidence of HIT was 0.2%; however,
      the estimated rate in patients exposed to heparin for more than 4 days was 1.2%.
      Compared with historical HIT cases, the rate of thrombosis was reduced from 50%
      to 29% (p=0.39) during surveillance. The only patient factor associated with
      increased risk was the presence of cancer (p=0.03). This pharmacy surveillance
      method may have a role in improving outcomes of HIT.

PMID- 10939560
TI  - Phytoestrogens as therapeutic alternatives to traditional hormone replacement in
      postmenopausal women.

PMID- 10939561
TI  - A vision of pharmacy's future roles, responsibilities, and manpower needs in the
      United States.

PMID- 10939562
TI  - Seizure recurrence in childhood epilepsy: "the future ain't what it used to be".

PMID- 10939563
TI  - Predictors of multiple seizures in a cohort of children prospectively followed
      from the time of their first unprovoked seizure.
AB  - The objective of this study was to assess the risk of multiple recurrences after
      an initial seizure recurrence in childhood. In a prospective study, 407 children
      were followed for a mean of 9.6 years from the time of their first unprovoked
      seizure. Data regarding each seizure recurrence were obtained and analyzed using
      statistical methods for survival analysis. The cumulative risk of a second
      seizure was 29%, 37%, 43%, and 46% at 1, 2, 5, and 10 years, respectively. Of the
      182 children who experienced a second seizure, 131 (72%) experienced a third
      seizure, 105 (58%) have had 4 or more seizures, and 52 (29%) have experienced 10
      or more seizures. The cumulative risk of a third seizure was 57%, 63%, and 71% at
      1, 2, and 5 years, respectively, after the second seizure. After a third seizure,
      the cumulative risk of another seizure was 69%, 72%, and 81% at 1, 2, and 5
      years, respectively. After a second seizure, factors associated with an increased
      risk of additional recurrences included a remote symptomatic etiology (rate ratio
      = 1.7) and the occurrence of a second seizure within 6 months of the first
      seizure (rate ratio = 1.7). After a second seizure, the risk of subsequent
      seizures was greater than 50% even in the lowest risk group. With the exception
      of etiology, factors associated with an increased risk of multiple recurrences
      after the initial seizure were different than those associated with multiple
      recurrences after a second seizure. Factors associated with multiple recurrent
      seizures may be different than those associated with an initial recurrence. As
      most patients who experience a second seizure experience further seizures, these
      data suggest that two seizures are a sufficient epidemiological criterion for the
      definition of epilepsy.

PMID- 10939564
TI  - Alzheimer's disease cybrids replicate beta-amyloid abnormalities through cell
      death pathways.
AB  - Alzheimer's disease (AD) is characterized by the deposition in brain of beta
      amyloid (Abeta) peptides, elevated brain caspase-3, and systemic deficiency of
      cytochrome c oxidase. Although increased Abeta deposition can result from
      mutations in amyloid precursor protein or presenilin genes, the cause of
      increased Abeta deposition in sporadic AD is unknown. Cytoplasmic hybrid
      ("cybrid") cells made from mitochondrial DNA of nonfamilial AD subjects show
      antioxidant-reversible lowering of mitochondrial membrane potential (delta(gYm),
      secrete twice as much Abeta(1-40) and Abeta(1-42), have increased intracellular
      Abeta(1-40) (1.7-fold), and develop Congo red-positive Abeta deposits. Also
      elevated are cytoplasmic cytochrome c (threefold) and caspase-3 activity
      (twofold). Increased AD cybrid Abeta(1-40) secretion was normalized by inhibition
      of caspase-3 or secretase and reduced by treatment with the antioxidant S(
      )pramipexole. Expression of AD mitochondrial genes in cybrid cells depresses
      cytochrome c oxidase activity and increases oxidative stress, which, in turn,
      lowers delta(psi)m. Under stress, cells with AD mitochondrial genes are more
      likely to activate cell death pathways, which drive caspase 3-mediated Abeta
      peptide secretion and may account for increased Abeta deposition in the AD brain.
      Therapeutic strategies for reducing neurodegeneration in sporadic AD can address
      restoration of delta(psi)m and reduction of elevated Abeta secretion.

PMID- 10939565
TI  - A novel locus for dominant cerebellar ataxia (SCA14) maps to a 10.2-cM interval
      flanked by D19S206 and D19S605 on chromosome 19q13.4-qter.
AB  - Dominantly inherited, late-onset pure cerebellar ataxia is a group of genetically
      heterogeneous neurodegenerative disorders. Approximately half of these disorders
      in the Japanese population are caused by moderate expansion of a CAG repeat in
      the coding region of the CACNA1A gene on chromosome 19p13 (SCA6). However,
      neither the loci nor the specific mutations for the remaining disorders have been
      determined. We performed systematic linkage analysis in a three-generation
      Japanese family with a locus or mutation that differed from those of known
      spinocerebellar ataxias. The family members with a late onset (> or =39 years
      old) exhibited pure cerebellar ataxia, whereas those with an early onset (< or
      =27 years old) first showed intermittent axial myoclonus followed by ataxia.
      Other neurological signs were sparse, and neuroimaging studies revealed that
      atrophy was confined to the cerebellum. Multipoint analysis and haplotype
      reconstruction ultimately traced this novel spinocerebellar ataxia locus (SCA14)
      to a 10.2-cM interval flanked by D19S206 and D19S605 on chromosome 19q13.4-qter
      (Zmax = 4.08, corrected for age-dependent penetrance).

PMID- 10939566
TI  - Sequence specificity of aminoglycoside-induced stop condon readthrough: potential
      implications for treatment of Duchenne muscular dystrophy.
AB  - As a result of their ability to induce translational readthrough of stop codons,
      the aminoglycoside antibiotics are currently being tested for efficacy in the
      treatment of Duchenne muscular dystrophy patients carrying a nonsense mutation in
      the dystrophin gene. We have undertaken a systematic analysis of aminoglycoside
      induced readthrough of each stop codon in human tissue culture cells using a dual
      luciferase reporter system. Significant differences in the efficiency of
      aminoglycoside-induced readthrough were observed, with UGA showing greater
      translational readthrough than UAG or UAA. Additionally, the nucleotide in the
      position immediately downstream from the stop codon had a significant impact on
      the efficiency of aminoglycoside-induced readthrough in the order C > U > A > or
      = G. Our studies show that the efficiency of stop codon readthrough in the
      presence of aminoglycosides is inversely proportional to the efficiency of
      translational termination in the absence of these compounds. Using the same
      assay, we analyzed a 33-base pair fragment of the mouse dystrophin gene
      containing the mdx premature stop codon mutation UAA (A), which is also the most
      efficient translational terminator. The additional flanking sequences from the
      dystrophin gene do not significantly change the relatively low-level
      aminoglycoside-induced stop codon readthrough of this stop codon. The
      implications of these results for drug efficacy in the treatment of individual
      patients with Duchenne muscular dystrophy or other genetic diseases caused by
      nonsense mutations are discussed.

PMID- 10939567
TI  - Clinical and molecular genetic spectrum of autosomal dominant Emery-Dreifuss
      muscular dystrophy due to mutations of the lamin A/C gene.
AB  - Emery-Dreifuss muscular dystrophy (EDMD) is characterized by early contractures
      of the elbows and Achilles tendons, slowly progressive muscle wasting and
      weakness, and life-threatening cardiomyopathy with conduction blocks. We recently
      identified LMNA encoding two nuclear envelope proteins, lamins A and C, to be
      implicated in the autosomal dominant form of EDMD. Here, we report on the
      variability of the phenotype and spectrum of LMNA mutations in 53 autosomal
      dominant EDMD patients (36 members of 6 families and 17 sporadic cases). Twelve
      of the 53 patients showed cardiac involvement exclusively, although the remaining
      41 all showed muscle weakness and contractures. We were able to identify a common
      phenotype among the patients with skeletal muscle involvement, consisting of
      humeroperoneal wasting and weakness, scapular winging, rigidity of the spine, and
      elbow and Achilles tendon contractures. The disease course was generally slow,
      but we observed either a milder phenotype characterized by late onset and a mild
      degree of weakness and contractures or a more severe phenotype with early
      presentation and a rapidly progressive course in a few cases. Mutation analysis
      identified 18 mutations in LMNA (i.e., 1 nonsense mutation, 2 deletions of a
      codon, and 15 missense mutations). All the mutations were distributed between
      exons 1 and 9 in the region of LMNA that is common to lamins A and C. LMNA
      mutations arose de novo in 76% of the cases; 2 of these de novo mutations were
      typical hot spots, and 2 others were identified in 2 unrelated cases. There was
      no clear correlation between the phenotype and type or localization of the
      mutations within the gene. Moreover, a marked inter- and intra-familial
      variability in the clinical expression of LMNA mutations exists, ranging from
      patients expressing the full clinical picture of EDMD to those characterized only
      by cardiac involvement, which points toward a significant role of possible
      modifier genes in the course of this disease. In conclusion, the high proportion
      of de novo mutations together with the large spectrum of both LMNA mutations and
      the expression of the disease should now prompt screening for LMNA in familial
      and sporadic cases of both EDMD and dilated cardiomyopathy associated with
      conduction system disease.

PMID- 10939568
TI  - Perilesional gliosis and seizure outcome: a study based on magnetization transfer
      magnetic resonance imaging in patients with neurocysticercosis.
AB  - We studied the effect of perilesional gliosis on seizure recurrence after
      stopping antiepileptic drug (AED) therapy in 108 patients with a solitary
      cysticercal brain cyst. All patients received albendazole therapy in the
      beginning, and magnetic resonance imaging (MRI) done after 2 seizure-free years
      showed complete disappearance of the lesion in 67, partial degeneration in 12,
      and healing by calcification in 29. The gliosis, which was not visible on initial
      MRI, was observed near the lesion in 22 (20%) patients on T1-weighted
      magnetization transfer spin-echo (MTSE) MRI. Initial seizure control was
      difficult with single AED therapy in 16 of 22 patients with gliosis but only in 8
      of 86 patients without gliosis. On stopping AED therapy, patients with
      perilesional gliosis had a higher incidence of seizure recurrence (19 of 22
      patients) compared with those who did not demonstrate gliosis (9 of 86 patients).
      The presumption that gliosis visible on MTSE MRI correlates with seizure
      recurrence had a high specificity (96%) but only moderate sensitivity (68%). Our
      findings suggest that there is a group of patients with neurocysticercosis in
      whom the risk of seizure recurrence is actually high. Several such patients have
      perilesional gliosis that can be identified on T1-weighted MTSE MRI. These
      patients probably need long-term AED administration.

PMID- 10939569
TI  - The epidemiology of pathogenic mitochondrial DNA mutations.
AB  - During the past decade, there have been many descriptions of patients with
      neurological disorders due to mitochondrial DNA (mtDNA) mutations, but the extent
      and spectrum of mtDNA disease in the general population have not yet been
      defined. Adults with suspected mtDNA disease in the North East of England were
      referred to a single neurology center for investigation over the 10-year period
      from 1990 to 1999 inclusive. We defined the genetic defect in these individuals.
      For the midyear period of 1997, we calculated the minimum point prevalence of
      mtDNA disease in the adults of working age (> 16-<60 years old for female
      subjects and <65 years old for male subjects) and the minimum prevalence of
      adults and children (<60 years for female subjects, <65 years for male subjects)
      at risk of developing mtDNA disease. mtDNA defects caused disease in 6.57 per
      100,000 individuals in the adult population of working age, and 7.59 per 100,000
      unaffected adults and children were at risk of developing mtDNA disease. Overall,
      12.48 per 100,000 individuals in the adult and child population either had mtDNA
      disease or were at risk of developing mtDNA disease. These results reflect the
      minimum prevalence of mtDNA disease and pathogenic mtDNA mutations and
      demonstrate that pathogenic mtDNA mutations are a common cause of chronic
      morbidity. These findings have resource implications, particularly for supportive
      care and genetic counseling.

PMID- 10939570
TI  - Progressive loss of cortical acetylcholinesterase activity in association with
      cognitive decline in Alzheimer's disease: a positron emission tomography study.
AB  - We measured brain acetylcholinesterase activity in 30 patients with Alzheimer's
      disease (AD) and 14 age-matched controls by positron emission tomography (PET)
      and using a carbon 11-labeled acetylcholine analogue. Seven AD patients had
      repeat PET scans. The k3 values were calculated as an index of
      acetylcholinesterase activity in a three-compartment analysis using the
      metabolite corrected arterial input function. Twenty-eight of the 30 AD patients
      (14 each in the early and late onset subgroups) were retained in the study so as
      to equalize the range and average severity of cognitive impairment within the
      early and late onset subgroups. The k3 values were significantly reduced in the
      neocortex, hippocampus, and amygdala in the early onset AD patients, although the
      k3 values were significantly reduced only in the temporoparietal cortex and
      amygdala in the late onset AD patients. In the longitudinal study, all 7 repeat
      AD patients showed further reduction of cortical k3 values in the second PET
      scans, with a mean interval of 2 years, suggesting a progressive loss of the
      ascending cholinergic system from the nucleus basalis of Meynert in AD. In 37 AD
      patients, there was a highly significant correlation between the cortical k3
      values and Mini-Mental State Examination scores, supporting the cholinergic
      hypothesis in AD.

PMID- 10939571
TI  - Differences in the Abeta40/Abeta42 ratio associated with cerebrospinal fluid
      lipoproteins as a function of apolipoprotein E genotype.
AB  - The epsilon4 allele of apolipoprotein E (ApoE) is a risk factor for Alzheimer's
      disease (AD). ApoE, which is important for lipid metabolism, is also a major
      constituent of cerebrospinal fluid (CSF) lipoproteins (LPs). Although ApoE in the
      CSF is derived from the central nervous system, the relation between LP
      metabolism in plasma and CSF is not clear. Soluble amyloid-beta (Abeta) protein
      may normally be associated with CSF LPs. It is converted in AD to a fibrillar
      form in brain parenchyma. ApoE and CSF LPs may regulate this process. The purpose
      of this study was to characterize CSF LPs from healthy, cognitively normal,
      fasted, elderly individuals at different risk for AD based on ApoE genotype.
      Lipid composition of CSF LPs did not differ with ApoE genotype. Interestingly,
      plasma and CSF high-density lipoprotein (HDL) cholesterol and apolipoprotein AI
      (ApoAI) levels were correlated. Importantly, as assessed by size-exclusion
      chromatography, Abeta in CSF coeluted in fractions containing LPs and was
      influenced by ApoE genotype: E4-positive subjects displayed significant
      elevations in Abeta40/Abeta42 ratios. These results suggest that plasma ApoAI/HDL
      levels can influence CSF ApoAI/HDL levels and that interactions between Abeta and
      central nervous system LPs may reflect changes in brain Abeta metabolism before
      the onset of clinical disease.

PMID- 10939573
TI  - The acute behavioral syndrome of anterior thalamic infarction: a prospective
      study of 12 cases.
AB  - Using systematic investigations, including neurological and neuropsychological
      examinations and computed tomography and magnetic resonance imaging analyzed on
      anatomical maps, we prospectively studied 12 patients (age range, 63+/-19 years)
      with an isolated anterior thalamic infarct. They had acute, severe, perseverative
      behavior, which was apparent in thinking, speech, and all memory and executive
      tasks, combined with increased sensitivity to interference. They also showed
      superimposition of mental activities normally processed sequentially (e.g.,
      giving biographical information while working on a calculation test), which we
      called palipsychism (from the Greek palin [again] and the Greek psyche [soul]).
      In addition, all 12 patients (8 with a left-sided infarct, 4 with a right-sided
      infarct) had word-finding difficulties, 7 of 12 with impaired naming, 8 of 12
      with dysarthria, and 5 of 12 with hypophonia. Comprehension, repetition, written
      abilities, and reasoning were consistently preserved, but apathy was usual. All
      patients had anterograde memory impairment, with a delayed recall deficit,
      primarily verbal in left-sided infarcts and visuospatial in right-sided infarcts.
      Dysexecutive features such as difficulty in programming motor sequences were
      always present. Visual neglect or topographic disorientation was found in 3
      patients. Magnetic resonance imaging emphasized involvement of the anterior group
      of thalamic nuclei, the mamillothalamic tract, and the anterior part of the
      internal medullary lamina, with structural sparing of the dorsomedial and
      ventrolateral nuclei. Sequential follow-up examinations showed spectacular
      improvement within a few months, with the only significant persisting
      abnormalities being memory dysfunction and apathy. The acute behavioral syndrome
      of anterior thalamic infarction is dominated by palipsychism, which corresponds
      to an overlap of sequential cognitive processes in two or more domains. Its
      association with severe perseverative behavior with increased sensitivity to
      interference, anterograde memory retrieval deficit, intrusions, naming
      difficulties with dysarthria and hypophonia, and apathy is suggestive of this
      type of infarct.

PMID- 10939572
TI  - HLA-DR15 is associated with lower age at onset in multiple sclerosis.
AB  - To date, more than a dozen studies have investigated the role of HLA genes in
      determining clinical course and disease severity in multiple sclerosis (MS); in
      each of these studies, however, patient sample size has been small, and no
      consistent pattern has emerged from the results. For the present study, we
      determined HLA class II genotypes and catalogued clinical and demographic data
      for a total of 948 patients, making our data set the largest ever used to
      investigate HLA genes in MS. Our goals were both to investigate the impact of HLA
      DRB1 alleles on clinical course and disease severity in MS and to compare the
      frequencies of the established susceptibility allele DR15 in various
      clinicodemographic subgroups of MS patients. We found that, in addition to DR15,
      DR17 is positively associated with susceptibility to MS; that none of the HLA
      DRB1 alleles influences course or outcome in MS; that carriers of DR15 are prone
      to MS development at an earlier age than noncarriers; and that differences in
      DR15 positivity rates, after stratification for diagnostic category and
      examination results, seem to reflect a gradient of phenocopy contamination, with
      rates increasing in proportion to the degree of clinical or paraclinical
      verification of the MS diagnosis.

PMID- 10939574
TI  - The fate of hypoxic tissue on 18F-fluoromisonidazole positron emission tomography
      after ischemic stroke.
AB  - We studied 24 patients up to 51 hours after ischemic stroke using 18F
      fluoromisonidazole positron emission tomography to determine the fate of hypoxic
      tissue likely to represent the ischemic penumbra. Areas of hypoxic tissue were
      detected on positron emission tomography in 15 patients, and computed tomography
      was available in 12 patients, allowing comparison with the infarct volume to
      determine the proportions of the hypoxic tissue volume that infarcted and
      survived. The proportion of patients with hypoxic tissue and the amount of
      hypoxic tissue detected declined with time. On average, 45% of the total hypoxic
      tissue volume survived and 55% infarcted. Up to 68% (mean, 17.5%) of the infarct
      volume was initially hypoxic. Most of the tissue "initially affected" proceeded
      to infarction. We correlated hypoxic tissue volumes with neurological and
      functional outcome assessed using the National Institutes of Health Stroke Scale,
      Barthel Index, and Rankin Score. Initial stroke severity correlated significantly
      with the "initially affected" volume, neurological deterioration during the first
      week after stroke with the proportion of the "initially affected" volume that
      infarcted, and functional outcome with the infarct volume. Significant reductions
      in the size of the infarct and improved clinical outcomes might be achieved if
      hypoxic tissue can be rescued.

PMID- 10939575
TI  - Secondary decline in apparent diffusion coefficient and neurological outcomes
      after a short period of focal brain ischemia in rats.
AB  - This study was designed to characterize the initial and secondary changes of the
      apparent diffusion coefficient (ADC) of water with high temporal resolution
      measurements of ADC values and to correlate ADC changes with functional outcomes.
      Fourteen rats underwent 30 minutes of temporary middle cerebral artery occlusion
      (MCAO). Diffusion-, perfusion-, and T2-weighted imaging was performed during MCAO
      and every 30 minutes for a total of 12 hours after reperfusion (n = 6).
      Neurological outcomes were evaluated during MCAO, every 30 minutes for a total of
      6 hours and at 24 hours after reperfusion (n = 8). The decreased cerebral blood
      flow during MCAO returned to normal after reperfusion and remained unchanged
      thereafter. The decreased ADC values during occlusion completely recovered at 1
      hour after reperfusion. The renormalized ADC values started to decrease
      secondarily at 2.5 hours, accompanied by a delayed increase in T2 values. The ADC
      defined secondary lesion grew over time and was 52% of the ADC-defined initial
      lesion at 12 hours. Histological evaluation demonstrated neuronal damage in the
      regions of secondary ADC decline. Complete resolution of neurological deficits
      was seen in 1 rat at 1 hour and in 6 rats between 2.5 and 6 hours after
      reperfusion; no secondary neurological deficits were observed at 24 hours. These
      data suggest that (1) a secondary ADC reduction occurs as early as 2.5 hours
      after reperfusion, evolves in a slow fashion, and is associated with neuronal
      injury; and (2) renormalization and secondary decline in ADC are not associated
      with neurological recovery and worsening, respectively.

PMID- 10939576
TI  - Novel mutations, pseudo-dominant inheritance, and possible familial affects in
      patients with autosomal recessive juvenile parkinsonism.
AB  - Autosomal recessive juvenile parkinsonism is a hereditary neurodegenerative
      disorder, usually beginning before the age of 40. We found three exonic deletions
      and two novel point mutations (Arg33Stop and Cys431Phe) in six families with
      autosomal recessive juvenile parkinsonism. In 1 family, in which an autosomal
      dominant mode of inheritance was suspected, multiple mutant alleles were
      identified. Although a wide range of ages at onset was observed, there was no
      correlation between age at onset and genotype.

PMID- 10939578
TI  - Ramsay Hunt syndrome in children.
AB  - In a retrospective study, 52 children were diagnosed with Ramsay Hunt syndrome.
      The facial palsy was milder and complete recovery of the function was achieved in
      78.6% of patients. Associated cranial neuropathies were less common in children
      than in adults. The timing of vesicle appearance tended to be delayed in
      children. In preschool children, Ramsay Hunt syndrome was rare, although the
      frequency has recently increased. The syndrome is relatively common in older
      children. This study suggested that vaccination can prevent or reduce the
      occurrence of Ramsay Hunt syndrome.

PMID- 10939577
TI  - Dopaminergic therapy improves upper limb motor performance in aged rhesus
      monkeys.
AB  - The potential of dopaminergic treatments to improve upper limb motor movements
      was tested in 7 aged rhesus monkeys using L-3,4-dihydroxyphenylalanine (L-dopa)
      or the selective dopamine uptake inhibitor 1-2(bis[4-fluorophenyl] methoxy]ethyl)
      4-(3-phenylpropyl) piperazine hydrochloride (GBR-12909). Six young monkeys were
      studied for comparison. L-Dopa or GBR-12909 improved upper limb motor performance
      by up to 40% in the aged animals. At this point their performance was comparable
      to that of young adults. Dopaminergic therapy could be useful in elderly humans
      experiencing declines in upper limb motor functions.

PMID- 10939580
TI  - Lumbar artery compression by the diaphragmatic crus: a new etiology for spinal
      cord ischemia.
AB  - We describe a new cause of spinal cord ischemia illustrated by two cases-
      compression by the diaphragmatic crus of a lumbar artery giving rise to a spinal
      artery. The diagnosis has been established by dynamic spinal angiography, showing
      complete occlusion of the lumbar artery. Surgical section of the diaphragmatic
      crus prevents irreversible infarction.

PMID- 10939579
TI  - CB1 cannabinoid receptor induction in experimental stroke.
AB  - Cannabinoids protect cortical neurons from ischemic injury by interacting with
      CB1 receptors. Because a variety of neuroprotective genes are induced in cerebral
      ischemia, we examined the effect of experimental stroke, produced by 20 minutes
      of middle cerebral artery occlusion in rats, on CB1 receptor expression. Western
      blotting and immunohistochemistry showed that CB1 expression on neurons was
      increased in the arterial boundary zone of the cortical mantle, beginning by 2
      hours and persisting for 72 hours or more after ischemia These findings are
      consistent with a neuroprotective role for endogenous cannabinoid signaling
      pathways and with a potential therapeutic role in stroke for drugs that activate
      CB1 receptors.

PMID- 10939581
TI  - A de novo mutation in sporadic nocturnal frontal lobe epilepsy.
AB  - Autosomal dominant nocturnal frontal lobe epilepsy is sometimes due to mutations
      in CHRNA4. The commoner presentation of sporadic nocturnal frontal lobe epilepsy
      has not been associated with genetic defects. A 30-year-old woman diagnosed as
      having sporadic nocturnal frontal lobe epilepsy was found to have a de novo
      Ser252Leu CHRNA4 mutation. A pattern is emerging of site-specific mutation within
      the second transmembrane domain of CHRNA4 in association with autosomal dominant
      nocturnal frontal lobe epilepsy and sporadic nocturnal frontal lobe epilepsy in
      families with different ethnic backgrounds.

PMID- 10939582
TI  - "Stops walking when talking" does not predict falls in Parkinson's disease.

PMID- 10939583
TI  - Hypertension and white matter changes.

PMID- 10939584
TI  - Polymorphism at codon 129 of PRNP affects the phenotypic expression of
      Creutzfeldt-Jakob disease linked to E200K mutation.

PMID- 10939585
TI  - cdr2-specific CTLs are detected in the blood of all patients with paraneoplastic
      cerebellar degeneration analyzed.

PMID- 10939586
TI  - What is the role of activated Th1 cells in the cerebrospinal fluid of patients
      with paraneoplastic cerebellar degeneration?

PMID- 10939587
TI  - Vitamin D and seasonal fluctuations of gadolinium-enhancing magnetic resonance
      imaging lesions in multiple sclerosis.

PMID- 10939588
TI  - P190-B, a Rho-GTPase-activating protein, is differentially expressed in terminal
      end buds and breast cancer.
AB  - Microdissection and differential display PCR were used to identify genes
      preferentially expressed in the highly proliferative terminal end buds (TEBs) in
      the mammary gland of 45-day-old virgin rats. One clone exhibited 87% homology to
      the human p190-B gene encoding a novel Rho-Gap. Using in situ hybridization, p190
      B was detected in both the TEBs and the terminal ducts, with the highest
      expression observed in the outer layer of TEBs. During normal mammary gland
      development, p190-B mRNA expression was highest in the virgin mammary gland and
      decreased during late pregnancy and lactation. Interestingly, increased levels of
      p190-B mRNA relative to the normal mammary gland were seen in a subset of murine
      mammary tumors that appeared to be less well differentiated and potentially more
      aggressive. Transient transfection of a p190-B expression construct into MCF-10A
      human mammary epithelial cells resulted in disruption of the actin cytoskeleton,
      which suggests a role for p190-B in regulating the signaling pathways that
      influence cell migration and invasion. These results suggest that p190-B may be
      required for virgin mammary gland development, and its aberrant expression may
      occur in breast cancer.

PMID- 10939589
TI  - The heat shock protein 90 antagonist geldanamycin alters chaperone association
      with p210bcr-abl and v-src proteins before their degradation by the proteasome.
AB  - Several important signaling proteins including transcription factors and protein
      kinases depend on heat shock protein (Hsp)-90 for stability. p210bcr-abl, a
      protein expressed in chronic myelogenous leukemia, is functionally inhibited by
      the benzoquinone ansamycin herbimycin A. Benzoquinone ansamycins also bind to and
      inhibit the activity of Hsp90. We now demonstrate that p210bcr-abl is complexed
      with Hsp90 and its cochaperone p23 in K562 chronic myelogenous leukemia cells.
      Brief exposure to the benzoquinone ansamycin Hsp90 inhibitor geldanamycin (GA)
      decreases the association of p210bcr-abl with Hsp90 and p23 and increases its
      association with the chaperones Hsp70 and p60Hop. GA has a similar effect on
      chaperone association with v-src, another Hsp90-dependent oncogenic kinase. Loss
      of Hsp90/p23 association and acquisition of Hsp70/p60Hop association of both
      p210bcr-abl and v-src precede GA-induced degradation of these kinases. GA-induced
      degradation is mediated by the proteasome because proteasome inhibitors block the
      effects of GA, causing both p210bcr-abl and v-src to accumulate in a detergent
      insoluble cellular fraction. Both p210bcr-abl and v-src are more susceptible to
      GA-induced degradation than are their normal cellular counterparts, c-abl and c
      src.

PMID- 10939590
TI  - Differential requirements for ras and the retinoblastoma tumor suppressor protein
      in the androgen dependence of prostatic adenocarcinoma cells.
AB  - Prostate cells are dependent on androgen for proliferation, but during tumor
      progression prostate cancer cells achieve independence from the androgen
      requirement. We report that androgen withdrawal fails to inhibit cell cycle
      progression or influence the expression of cyclin-dependent kinase (CDK)/cyclins
      in androgen-independent prostate cancer cells, indicating that these cells signal
      for cell cycle progression in the absence of androgen. However, phosphorylation
      of the retinoblastoma tumor suppressor protein (RB) is still required for G1-S
      progression in androgen-independent cells, since the expression of constitutively
      active RB (PSM-RB) or p16ink4a caused cell cycle arrest and mimicked the effects
      of androgen withdrawal on downstream targets in androgen-dependent LNCaP cells.
      Since Ras is known to mediate mitogenic signaling to RB, we hypothesized that
      active V12Ras would induce androgen-independent cell cycle progression in LNCaP
      cells. Although V12Ras was able to stimulate ERK phosphorylation and induce
      cyclin D1 expression in the absence of androgen, it was not sufficient to promote
      androgen-independent cell cycle progression. Similarly, ectopic expression of
      CDK4/cyclin D1, which stimulated RB phosphorylation in the presence of androgen,
      was incapable of inactivating RB or driving cell cycle progression in the absence
      of androgen. We show that androgen regulates both CDK4/cyclin D1 and CDK2
      complexes to inactivate RB and initiate cell cycle progression. Together, these
      data show that androgen independence is achieved via deregulation of the androgen
      to RB signal, and that this signal can only be partially initiated by the Ras
      pathway in androgen-dependent cells.

PMID- 10939591
TI  - Adenovirus-mediated overexpression of p15INK4B inhibits human glioma cell growth,
      induces replicative senescence, and inhibits telomerase activity similarly to
      p16INK4A.
AB  - The genes encoding the cyclin-dependent kinase inhibitors p16INK4A (CDKN2A) and
      p15INK4B (CDKN2B) are frequently homozygously deleted in a variety of tumor cell
      lines and primary tumors, including glioblastomas in which 40-50% of primary
      tumors display homozygous deletions of these two loci. Although the role of p16
      as a tumor suppressor has been well documented, it has remained less well studied
      whether p15 plays a similar growth-suppressing role. Here, we have used
      replication-defective recombinant adenoviruses to compare the effects of
      expressing wild-type p16 and p15 in glioma cell lines. After infection, high
      levels of p16 and p15 were observed in two human glioma cell lines (U251 MG and
      U373 MG). Both inhibitors were found in complex with CDK4 and CDK6. Expression of
      p16 and p15 had indistinguishable effects on U251 MG, which has homozygous
      deletion of CDKN2A and CDKN2B, but a wild-type retinoblastoma (RB) gene. Cells
      were growth-arrested, showed no increased apoptosis, and displayed a markedly
      altered cellular morphology and repression of telomerase activity. Transduced
      cells became enlarged and flattened and expressed senescence-associated beta
      galactosidase, thus fulfilling criteria for replicative senescence. In contrast,
      the growth and morphology of U373 MG, which expresses p16 and p15 endogenously,
      but undetectable levels of RB protein, were not affected by exogenous
      overexpression of either inhibitor. Thus, we conclude that overexpression of p15
      has a similar ability to inhibit cell proliferation, to cause replicative
      senescence, and to inhibit telomerase activity as p16 in glioma cells with an
      intact RB protein pathway.

PMID- 10939592
TI  - Gastrin-releasing peptide is a mitogen and a morphogen in murine colon cancer.
AB  - Little is known about the factors involved in regulating the appearance, or
      differentiation, of solid tumors including those arising from the colon. We
      herein demonstrate that the mitogen gastrin-releasing peptide (GRP) is a
      morphogen, critically important in regulating the differentiation of murine colon
      cancer. Although epithelial cells lining the mouse colon do not normally express
      GRP and its receptor (GRP-R), both are aberrantly expressed by all better
      differentiated cancers in wild-type C57BL/6J mice treated with the carcinogen
      azoxymethane. Whereas small tumors in both wild-type and GRP-R-deficient (i.e.,
      GRP-R-/-) mice are histologically similar, larger tumors become better
      differentiated in the former but degenerate into more poorly differentiated
      mucinous adenocarcinomas in the latter. This alteration in phenotype is
      attributable to GRP increasing focal adhesion kinase expression in GRP-R
      expressing tumors. Consistent with GRP acting as a mitogen, GRP/GRP-R
      coexpressing tumors in wild-type animals also contain more proliferating cells
      than those occurring in GRP-R-/- mice. Yet tumors are similarly sized in animals
      of either genotype receiving azoxymethane for identical times, a finding
      attributable to the significantly higher number of apoptotic cells detected in
      GRP/GRP-R coexpressing cancers. Thus, these findings indicate that although GRP
      is a mitogen, aberrant expression does not result in increased tumor growth.
      Rather, the mitogenic properties of GRP are subordinate to it acting as a
      morphogen, where it and its receptor are critically involved in regulating colon
      cancer histological progression by promoting a well-differentiated phenotype.

PMID- 10939593
TI  - Transformation of mortal human fibroblasts and activation of a growth inhibitory
      pathway by the bovine papillomavirus E5 oncoprotein.
AB  - The 44-amino acid bovine papillomavirus E5 protein induces tumorigenic
      transformation of immortal rodent fibroblasts by binding to and activating the
      platelet-derived growth factor beta receptor (PDGFbetaR). Here E5 was expressed
      in mortal human diploid fibroblasts (HDFs), which lack the accumulated genetic
      changes that are present in immortal rodent cells. E5 induced focus formation and
      morphological transformation of HDFs without inducing anchorage independence or
      immortalization. Similar effects were observed with the v-sis and neu* oncogenes.
      E5-PDGFbetaR complexes were observed in the E5-expressing HDFs, as was
      constitutive PDGFbetaR activation, which was required for the transforming
      activity of E5. The E5 HDFs attained a higher saturation density than the control
      cells, expressing increased levels of hyperphosphorylated retinoblastoma protein
      at subconfluent densities. However, when these cells reached confluence, growth
      inhibition accompanied by dramatic down-regulation of the PDGFbetaR, and
      retinoblastoma protein was induced apparently by a factor secreted into the
      medium. This may represent a novel negative feedback mechanism controlling
      PDGFbetaR-induced proliferation and thereby protecting against complete
      transformation.

PMID- 10939594
TI  - Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential
      for tumor cell survival and entry into mitosis.
AB  - Pin1, a member of the parvulin family of peptidyl-prolyl cis-trans isomerases
      (PPIases) has been implicated in the G2-M transition of the mammalian cell cycle.
      Pin1 interacts with a series of mitotic phosphoproteins, including Polo-like
      kinase-1, Cdc25C, and Cdc27, and is thought to act as a phosphorylation-dependent
      PPIase for these target molecules. Pin1 recognizes phosphorylated serine-proline
      or threonine-proline peptide-bonds in test substrates up to 1300-fold better than
      in the respective unphosphorylated peptides. To test directly whether Pin1
      regulates the G2-M transition and/or progression through mitosis by catalyzing
      phosphorylation-dependent prolyl isomerization of essential mitotic targets, we
      examined the consequences of Pin1 depletion, achieved by (a) overexpression of
      Pin1 antisense RNA, (b) overexpression of dominant-negative Pin1, and (c) by a
      known small-molecule Pin1-PPIase inhibitor, juglone. The results of all of the
      three lines of investigation show that the catalytic activity of Pin1 is
      essential for tumor cell survival and entry into mitosis.

PMID- 10939595
TI  - Detection of breast cancer cells in the bone marrow or peripheral blood: methods
      and prognostic significance.
AB  - Tumor cells can reach every anatomic district, organ and tissue through the
      peripheral blood circulation. Tumor cell shedding is considered an early event in
      the multi-phase process of metastasis, and the possibility of detecting tumor
      cells in the bloodstream and/or bone marrow before clinical evidence of distant
      metastases needs to be explored. The use of new sophisticated diagnostic and
      investigative techniques has boosted the study of tumor cell contamination of
      bone marrow and peripheral blood. Molecular techniques, such as reverse
      transcriptase polymerase chain reaction, may be useful tools to reach this
      target, but, today, immunocytochemistry is still considered the gold standard to
      assess new techniques to detect isolated tumor cells in hematopoietic tissue.
      Little is known about the biology of isolated tumor cells in the peripheral blood
      or bone marrow. Two crucial points need to be evaluated: the identification of
      specific markers of breast cancer cells with clonogenic potential and their
      biologic properties, and the prognostic impact of the detection of isolated tumor
      cells in the bone marrow or peripheral blood stem cell collections.

PMID- 10939596
TI  - Ovarian ablation for premenopausal early-stage breast cancer: an update.
AB  - Ovarian ablation is the oldest form of systemic treatment of breast cancer and
      consists of removal of the main source of estrogen biosynthesis in premenopausal
      women: Over the last century several different means of stopping ovarian function
      have been studied: surgical oophorectomy, ovarian irradiation, and more recently,
      chemical castration by gonadotropin-releasing hormone analog therapy. In
      unselected patients the response rate to ovarian ablation is of about 35% but the
      likelihood of response is considerably higher for patients with hormonal receptor
      positive tumors, the therapy being most effective in women who are actively
      menstruating. In spite of this evidence, the role of ovarian ablation in the
      management of early-stage breast cancer still remains controversial. Here we
      review current evidence supporting the value of this ablative procedure as an
      adjuvant and update ongoing clinical research to refine our knowledge about its
      use.

PMID- 10939597
TI  - Overhead electricity power lines and childhood leukemia: a registry-based, case
      control study.
AB  - AIMS AND BACKGROUND: To evaluate the role of exposure to low-frequency
      electromagnetic fields generated by overhead power lines on the risk of childhood
      leukemia, we carried out a case-control study in the area (Varese province)
      covered by the Lombardy Cancer Registry. METHODS AND STUDY DESIGN: Exposure to
      magnetic fields was estimated using line load data and the distance between
      subjects' homes and the nearest power line. A total of 101 cases and 412 controls
      were investigated. RESULTS: Twenty subjects (9 cases and 11 controls) were
      considered exposed. A significant fourfold increase in risk for leukemia in
      exposed subjects and a dose-response relationship were found. The risk was higher
      than that reported by other studies. Potential biases related to the
      representativity of controls and validity of exposure assessment do not seem to
      have influenced the risk estimates. CONCLUSIONS: We suggest that measures to
      remedy residential exposure should be taken wherever practicable.

PMID- 10939598
TI  - Information and awareness of diagnosis and progression of cancer in adult and
      elderly cancer patients.
AB  - AIMS AND BACKGROUND: The present study examines the effects of physicians'
      attitudes towards providing information about diagnosis and progression of
      disease to cancer patients. The aims of the study were to: a) establish how many
      patients (subdivided into an adult and an elderly group) were informed and how
      many were aware of the diagnosis and progression of disease; b) identify possible
      significant differences between the two groups as regards information and
      awareness of disease; c) determine possible significant differences between
      information about diagnosis and disease progression and between awareness of
      diagnosis and progression within each group, and d) identify the patients' real
      needs. METHODS AND STUDY DESIGN: A total of 311 adults and 92 elderly cancer
      patients were enrolled in the study. A semi-structured clinical interview was
      employed to assess the "information" and "awareness" variables and the patients'
      needs. Statistical analyses were made with the chi squared test. RESULTS:
      Significant differences were observed between the two groups as regards
      information and awareness of diagnosis. Within each group, we found significant
      differences between information about diagnosis and progression and between
      awareness of diagnosis and progression. The principle needs expressed in both
      groups were to have clear information and emotional containment. CONCLUSIONS: The
      results of the study showed that physicians informed a greater number of adult
      than elderly patients and more often during the early rather than in the more
      advanced stages of the disease.

PMID- 10939599
TI  - Delay in diagnosis of high-grade osteosarcoma of the extremities. Has it any
      effect on the stage of disease?
AB  - In 965 patients with high-grade osteosarcoma of the extremities, we investigated
      the correlation between diagnostic delay and the stage of the tumor at
      presentation. The mean interval between the onset of first symptoms and the final
      diagnosis was significantly shorter in patients with metastatic disease than in
      patients with localized disease at the time of the diagnosis. The difference was
      due to a late presentation of patients with localized disease to the physician
      and not to delays in performing radiologic examinations or in referring patients
      to a specialized hospital for biopsy and treatment. We conclude that in high
      grade osteosarcoma of the extremity the shorter interval between onset of
      symptoms and diagnosis observed in patients with disseminated disease at the time
      of the diagnosis reflects a more aggressive behavior of tumors that are
      metastatic at presentation.

PMID- 10939600
TI  - A phase II study of paclitaxel/cisplatin combination in patients with metastatic
      breast cancer refractory to anthracycline-based chemotherapy.
AB  - AIMS AND BACKGROUND: To investigate the safety and efficacy of a paclitaxel and
      cisplatin regimen in a selected group of metastatic breast cancer patients with
      primary or acquired chemo-resistance to anthracycline-based chemotherapy.
      PATIENTS AND METHODS: Thirty-eight consecutive women with metastatic breast
      cancer (PS < or =2) were entered in this phase II trial; all patients had been
      previously treated for metastatic disease with chemotherapy containing
      anthracyclines and had shown a progression of the disease during drug
      administration or after a clinical response lasting less than 6 months. Fifteen
      patients had received 2 or more chemotherapeutic regimens for advanced disease;
      31 patients had > or =2 sites of metastatic disease. Paclitaxel (135 mg/m2) was
      administered iv by a 3-hr infusion followed by iv infusion of cisplatin (75
      mg/m2) on day 1, every 3 weeks for 6 cycles. After the completion of the planned
      chemotherapy administration, 9 responsive patients continued to receive
      paclitaxel alone (175 mg/m2) iv, on day 1, every 3 weeks, until disease
      progression or unacceptable toxicity. RESULTS: A partial clinical response was
      recorded in 17 cases (45%; 95% CI, 30-64%). The median duration of overall
      response was 8 months; for the 9 responsive patients who continued treatment with
      paclitaxel alone, 4 had maintained the partial clinical response at the median
      follow-up of 24 months from the onset of therapy. The median time to progression
      was 6 months and median overall survival 8 months. Neurotoxicity was the most
      frequent adverse effect and caused treatment discontinuation in 5 cases for grade
      3-4 paresthesia and/or an arthralgia/myalgia syndrome. Grade 3-4 neutropenia
      occurred in 16 patients (44%). CONCLUSIONS: Paclitaxel/cisplatin is an active
      regimen for the treatment of patients with metastatic breast cancer refractory to
      anthracycline-based chemotherapy. However, the cumulative neurotoxicity should
      limit the efficacy of prolonged paclitaxel monotherapy in responsive patients.

PMID- 10939602
TI  - Treatment of cancer of the base of the tongue and glosso-epiglottic region: a
      multicenter Italian survey. GLOCC Group. Gruppo di Lavoro in Oncologia Cervico
      Cefalica.
AB  - BACKGROUND: The current treatment options for cancer of the base of the tongue
      and glosso-epiglottic region are surgery, radiotherapy, or a combination of both
      modalities. Comparisons between different modalities are not common in the
      literature, and a real standard of treatment has not yet been established. The
      purpose of our study was to evaluate the results of treatment in a large series
      of patients from 18 Italian institutions in relation to the main treatment
      adopted. METHODS: The present study is a retrospective survey. The series was
      divided into a combined surgery group and a radiotherapy group. The Kaplan-Meier
      method and the log-rank test were used for survival calculations and comparisons.
      RESULTS: Eight hundred patients were registered (25.7% stage III and 62% stage
      IV), 336 in the surgery and 372 in the radiotherapy group. Conventional
      fractionation was adopted in almost all cases. The five-year overall and disease
      free survival of the whole series was 32% and 38%, respectively. Survival was
      slightly better for patients with tumors of the glosso-epiglottic region than for
      those with a tumor of the base of the tongue. Five-year disease-free survival was
      55% for patients treated with surgery +/- radiochemotherapy and 26% for those
      submitted to radiotherapy alone or in combination with chemotherapy. As far as
      the total dose and the treatment duration were concerned, only 26% of the
      patients of the radiotherapy group met the established criteria of adequacy, but
      in patients with adequate radiation the control rate was better only for small
      tumors (T1-T2). CONCLUSIONS: The results in patients treated with surgery +/-
      postoperative radiotherapy were similar to or better than those reported in the
      best series in the literature. By contrast, the survival rate of irradiated
      patients was lower than those reported by other centers.

PMID- 10939601
TI  - 5-fluorouracil plus folinic acid with or without ifosfamide in advanced
      colorectal cancer: a phase II randomized trial.
AB  - AIM: This phase II trial evaluated the biomodulation of 5-fluorouracil (5-FU)
      plus folinic acid (FA) with or without ifosfamide (IFO) in chemotherapy-naive
      patients with colorectal cancer. PATIENTS AND METHODS: Forty-eight patients were
      randomized to receive: FA (25 mg/m2 iv bolus days 1 to 3), followed by 5-FU (750
      mg/m2 iv bolus days 1 to 3), arm A; or FA (25 mg/m2 iv bolus days 1 to 3),
      followed by 5-FU (750 mg/m2 iv bolus days 1 to 3) plus IFO (2,000 mg/m2 in 1000
      mL 5% dextrose in a 2-hr infusion, days 1 to 3), arm B. Mesna was added during
      and after IFO to prevent hemorrhagic cystitis. Treatment was repeated every 21
      days in both arms. RESULTS: Forty-five patients were assessable for response: in
      arm A, 5 patients achieved a partial response (overall response, 25%), and in arm
      B, 2 patients achieved a complete and 1 a partial response (overall response,
      12%). Time to failure was 3.5 months (range, 1-38) in patients treated with 5-FU
      plus FA, and 3 months (range, 1-21) in patients treated with the IFO combination.
      The median survival time was 13.5 months (range, 1-49 months) in arm A and 16
      months (range, 1-43 months) in arm B. Diarrhea, stomatitis and vomiting were the
      most common nonhematologic toxicities in both arms. The most notable hematologic
      toxicity was leukopenia; 15% and 20% of patients experienced grade 4 in arm A and
      arm B, respectively. CONCLUSIONS: IFO does not increase the activity of the 5-FU
      plus FA combination in advanced colorectal cancer.

PMID- 10939603
TI  - Clinical diagnostic application of 111In-DTPA-octreotide scintigraphy in small
      cell lung cancer.
AB  - Some years ago it was proved that a good percentage of small cell lung cancers,
      classified among cancers of the APUD system, produces somatostatin receptors that
      can be detected in vivo by scintigraphy with 111In-DTPA-octreotide. With the
      method in the whole body it is possible to identify the principal neoformation
      and the probable metastases. The authors present a study of 21 patients afflicted
      with small cell lung cancer diagnosed histologically. The study, carried out
      between January 1995 and December 1997, compared the radiologic iconography of
      the CT scan with the scintigraphic map obtained by a planar scintigraphy and in
      SPECT 1, 4 and 24-hr after iv injection of 110 MBq of 111In-DTPA-octreotide. The
      comparison was made with reference to the principal neoplasm and probable
      metastases. A scintigraphic study, a CT of restaging and a follow-up, done after
      3 and 6 months of chemotherapy, on 15 patients with cancer that produces
      somatostatin receptors proved that the neoplasm sometimes regresses and sometimes
      progresses. In the latter case, it is possible to identify cerebral, mediastinal
      and hepatic metastases with the administration of 200 microg of octreotide 3
      times a day for 7 days before the scintigraphy. In fact, the administration
      lowers background activity. The authors concluded that scintigraphy with 111In
      DTPA-octreotide plays an important part in the study of patients afflicted with
      small cell lung cancer. Scintigraphy identifies the subgroups of patients who can
      be cured with somatostatin analogues together with chemotherapy. Scintigraphy
      presents a good sensibility in the re-staging and in the follow-up of patients
      who are treated, even though it is difficult to identify subdiaphragmatic
      metastases where liver, spleen and kidney show an increase in 111In-DTPA
      octreotide.

PMID- 10939604
TI  - Adrenocorticotropic hormone secreting pituitary adenomas: analysis of growth
      fraction using the MIB-1 antibody.
AB  - AIMS AND BACKGROUND: Pituitary adenomas are usually considered well
      differentiated tumors, even if in about one third of cases they invade
      surrounding tissues, with the possibility of postoperative relapse after complete
      surgical removal. Adrenocorticotropic hormone (ACTH) secreting adenomas seem to
      be the most infiltrating subtype, with a higher incidence of recurrence. Ki-67 is
      a nuclear antigen which is easily detectable by means of the MIB-1 monoclonal
      antibody, and the labeling index (LI) obtained can be considered a marker of
      tumor proliferation. METHODS: In order to identify the growth fraction of these
      tumors we used the MIB-1 antibody to evaluate the expression of Ki-67 antibody in
      11 ACTH secreting pituitary adenomas and to compare it with the LI obtained in 98
      other hormone secreting or non-functioning pituitary adenomas consecutively
      operated on during a 40-month period. RESULTS: In relation to surgically verified
      infiltration of the sellar floor dura and bone, we identified eight non-invasive
      and three invasive ACTH secreting pituitary adenomas. All invasive tumors
      infiltrated the wall of the cavernous sinus (CS). The mean Ki-67 LI was 5.88 +/-
      9.13% versus 2.33 +/- 2.40% in non-ACTH secreting adenomas (P = 0.0025). It was
      13.27 +/- 15.42% in invasive and 3.11 +/- 4.37% in non-invasive ACTH adenomas,
      and 18.40 +/- 17.82% in patients over 50 years versus 3.10 +/- 4.09% in younger
      subjects (P = 0.02). CONCLUSIONS: Ki-67 LI is a useful marker in the
      determination of proliferative activity and invasiveness of anterior pituitary
      adenomas. Our data seem to confirm that ACTH secreting adenomas have a higher
      growth fraction than other pituitary adenomas and this observation presumably
      explains the higher incidence of relapse of these tumors even after
      macroscopically total removal.

PMID- 10939606
TI  - Papillary thyroid carcinoma and related thyroid neoplastic lesions: a light
      microscopic study with emphasis on nuclear changes.
AB  - A total of 187 thyroid lesions consisting of 2 cases of Grave's disease, 21 cases
      of multinodular goiter, 40 follicular adenomas and 124 low-grade papillary
      thyroid carcinomas were studied to identify intermediate neoplastic lesions in
      the spectrum of nuclear changes between benign reactive thyroid follicles and low
      grade thyroid papillary carcinoma. The lesions were examined and classified on
      the basis of the following nuclear features: fine chromatin seen in the thyroid
      papillary carcinomas and coarse chromatin seen in follicular carcinomas. Cases
      with Hurthle cell changes were excluded from the study. Cases with nuclei
      containing coarse chromatin were classified in the group of follicular adenomas
      with a coarse chromatin pattern. The neoplastic thyroid lesions containing fine
      chromatin showed a spectrum of nuclear changes ranging between reactive
      follicular lesions and papillary thyroid carcinoma with lymph node metastasis.
      Such lesions were classified as follicular adenomas with a fine chromatin
      pattern. The nuclei of these lesions were graded into mild to marked "nuclear
      atypia with a fine chromatin pattern". The degree of atypia depended on the
      degree and extent of nuclear changes. Encapsulated follicular adenomas with a
      fine chromatin pattern and with mild atypia (11 cases), moderate atypia (13
      cases), marked atypia (27 cases), and encapsulated or nonencapsulated papillary
      thyroid carcinoma were characterized by uniform nuclei; with mild, moderate and
      marked nuclear atypia in less than 2/3 of the cell population and marked nuclear
      atypia in more than 2/3 of the cell population; and measuring 5.4-6.3, 6.0-7.2,
      6.3-9 and 7.2-10 microns in diameter, respectively. Follow-up of cases of
      papillary thyroid carcinoma fulfilling the above criteria showed lymph node
      metastasis in 33% of cases, whereas follicular adenomas with a fine chromatin
      pattern, including cases originally diagnosed as papillary carcinoma, showed no
      evidence of lymph node or distant metastasis in a follow-up period of 30 months
      to 15 years. In the thyroid tissue surrounding papillary thyroid carcinoma or
      encapsulated follicular adenoma with a fine chromatin pattern and marked atypia,
      adenomatous nodules with a fine chromatin pattern and with low-grade nuclear
      atypia were identified. The adenomatous nodules with a fine chromatin pattern and
      with mild, moderate and marked atypia showed architectural, cytoplasmic and
      nuclear features similar to those of follicular adenoma with a fine chromatin
      pattern of the same grade. Of interest, a large number of cases of follicular
      adenoma with a fine chromatin pattern had areas with features of follicular
      adenoma with a coarse chromatin pattern.

PMID- 10939605
TI  - Preliminary study on immunoscintigraphy of a murine lymphoma using technetium-99M
      labeled chicken antibody.
AB  - AIMS AND BACKGROUND: Radiolabeled antibodies generated against tumor-associated
      antigens are used for immunoscintigraphy to detect tumors and tumor metastases.
      Although successful tumor imaging has been achieved using trace-labeled murine
      monoclonal antibodies, such antibodies often lead to the development of human
      anti-murine antibodies (HAMA), which limit their subsequent administration for
      tumor imaging and therapy. It has been reported recently that chicken polyclonal
      antibodies have high affinity and specificity for the antigen against which they
      are raised and do not have any immunological cross-reactivity with HAMA. METHODS:
      The present study deals with immunoscintigraphy of Dalton's lymphoma, an
      experimental tumor model using chicken antibodies generated against Dalton's
      lymphoma-associated antigen (DLAA) and labeled with technetium-99m ((99m)Tc).
      RESULTS: Scintigrams showed specific uptake of the radiolabel resulting in clear
      tumor images. The radioactivity uptake of the chicken anti-DLAA antibody was
      about twofold higher than that of the non-specific chicken antibody. CONCLUSIONS:
      The results demonstrate the potential of chicken antibody for in vivo
      radioimmunodetection and localization of tumors.

PMID- 10939608
TI  - Recurrent spontaneous pneumothorax following high-dose chemotherapy in a patient
      with non-seminomatous testicular cancer with pulmonary metastases.
AB  - With modern treatment modalities it is possible to obtain a long survival in
      patients with non-seminomatous testicular cancer. Chemotherapy is the mainstay of
      treatment in metastatic cases. High-dose chemotherapy and autologous peripheral
      blood stem cell transplantation is a good salvage treatment for recurrent cases.
      However, the modality has serious complications. We present a rare case of
      recurrent spontaneous pneumothorax due to rupture of residual cystic lesions
      after high-dose chemotherapy in a patient with pulmonary metastases. Such a
      situation has been rarely reported.

PMID- 10939607
TI  - Intrathyroid thyroglossal duct cyst simulating a thyroid nodule.
AB  - A case of intrathyroid thyroglossal duct cyst is reported. A 50-year-old woman
      presented with a right lateral neck mass that was clinically indistinguishable
      from a thyroid nodule. Ultrasound-guided fine-needle aspiration biopsy (US-FNAB)
      revealed normal-looking squamous cells. Right thyroid lobectomy was performed and
      microscopic examination revealed a cyst lined by squamous epithelium that was
      consistent with a thyroglossal duct cyst. The lesion was completely surrounded by
      normal thyroid tissue. Our experience suggests that intrathyroid thyroglossal
      duct cyst should be remembered in the differential diagnosis of a thyroid nodule.
      Detection of benign squamous cells by US-FNAB may be useful for ruling out the
      possibility of a cystic thyroid tumor.

PMID- 10939609
TI  - A case of mesothelioma of the tunica vaginalis testis, with involvement of the
      pleura and peritoneum.

PMID- 10939610
TI  - Adjuvant oophorectomy versus CMF in premenopausal node-positive breast cancer:
      long-term results of an experience at the Milan Cancer Institute.

PMID- 10939611
TI  - [Last news from ASCO 2000 in the topic of colorectal cancer] .

PMID- 10939613
TI  - "Oh wonderful stuff is skin. It's the stuff that keeps you in".

PMID- 10939612
TI  - [In Europe Anastrozole approved for first-line treatment of advanced breast
      cancer in postmenopausal patients].

PMID- 10939614
TI  - In vivo models of inflammation and matrix remodelling: classical to modern
      approaches.

PMID- 10939615
TI  - Neuroendocrine and immune interactions with airway macrophages.
AB  - Immune cells, including macrophages, are sources of many cytokines as well as a
      number of peptide hormones such as corticotropic releasing hormone and the
      endorphins. These mediators are involved in local immune regulation and may also
      function in an endocrine manner to influence the systemic hormonal response to
      stress. In turn, the major effectors of the systemic stress response, namely the
      glucocorticoids and the catecholamines, have been shown to modulate macrophage
      function. This review highlights some of what is known about neuroendocrine
      interactions with macrophages, and in particular, with airway macrophages, as
      modulation of airway macrophage function by neuroendocrine peptides is likely
      critical for the maintenance of lung homeostasis. The production of
      neuromediators (acetylcholine, catecholamines, sensory neuropeptides) and
      neuropeptide hormones (i.e. adrenocorticotropic hormone (ACTH) and beta
      endorphin), from airway macrophages is also discussed. We have defined airway
      macrophages as those cells that reside in the airway compartment (i.e. versus the
      interstitium) and provide the first line of defence to inhaled particles.

PMID- 10939616
TI  - In vitro cytokine mRNA expression in normal human peripheral blood mononuclear
      cells.
AB  - OBJECTIVE AND DESIGN: Normal human peripheral blood mononuclear cells (PBMC) were
      analyzed for basic profiles of mRNA expression of distinct genes during
      incubation in a standard cell culture system. MATERIAL: Human PBMC from healthy
      adult blood donors. METHODS: Steady-state mRNA expression was measured using a
      semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) assay.
      RESULTS: Shortly after isolation and cell seeding, mRNA levels of monocyte
      derived cytokines (IL-1alpha, IL-6, and TNF-alpha) were significantly increased,
      whereas lymphocyte-derived cytokines (IL-4, IFN-gamma) were not affected.
      Expression levels of monokines returned to basal within 24 h. At later stages of
      culture, the mRNA levels of all genes studied gradually increased and were
      significantly elevated after 96 h of incubation. CONCLUSIONS: Monokine and
      lymphokine mRNAs respond differently to cell culture even under control
      conditions. With regard to the enhanced mRNA expression of distinct cytokines in
      the early stages of culture, human PBMC should not be used for gene expression
      studies in vitro within 24 h of isolation.

PMID- 10939617
TI  - Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory
      role of STAT6.
AB  - OBJECTIVE AND DESIGN: The ability of interleukin-4 (IL-4) to modulate activation
      of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory
      cytokine expression and protect against liver injury induced by
      ischemia/reperfusion was assessed. MATERIALS AND SUBJECTS: C57BL/6 mice underwent
      90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with
      or without intravenous administration of 1 microg (0.5 microg just prior to
      ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of
      TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in
      liver nuclear extracts was assessed by mobility shift assay. RESULTS: Hepatic
      ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha
      (TNFalpha), induced significant neutrophil accumulation and liver injury.
      Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil
      accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation,
      but greatly increased the activation of STAT6. CONCLUSIONS: The data suggest that
      STAT6 activation by IL-4 may be responsible for the protective effects of this
      cytokine.

PMID- 10939618
TI  - Antimicrobial and cytotoxic activity of hypochlorous acid: interactions with
      taurine and nitrite.
AB  - OBJECTIVE: HOCl, a major bactericidal product of neutrophil MPO-halide system
      reacts with taurine to form taurine chloramine (TauCl), a less toxic anti
      inflammatory mediator. Recently, it has been reported that HOCl may also react
      with nitrite (NO2-), a major end-product of nitric oxide (NO) metabolism, to form
      very active oxidant, nitryl chloride (NO2Cl). The present study was conducted to
      elucidate the effect of nitrite on bactericidal and some immunoregulatory
      properties of HOCl and TauCl. MATERIALS: TauCl was prepared from NaOCl and
      taurine. The reaction was carried out at pH 5.0 and pH 7.4, in the presence or
      absence of nitrite. All reactions were monitored by UV absorption spectra.
      METHODS: Bactericidal activity of HOCl and TauCl in the presence of nitrite was
      tested by incubation of E. coli with the compounds and determined by the pour
      plate method. To test the effect of the compounds on activity of inflammatory
      cells, murine peritoneal neutrophils (PMN) and macrophages were used. The cells
      were activated in vitro with either LPS, IFN-gamma or zymosan and the production
      of following mediators was measured: reactive oxygen species using luminol
      dependent chemiluminescence; nitric oxide by Griess reaction; TNF-alpha using
      capture ELISA. In addition, we tested the effect of HOCl and TauCl on activity of
      myeloperoxidase (MPO). RESULTS: At physiological pH nitrite reacts with HOCl but
      not with TauCl. This reaction was abolished in the presence of taurine. Nitrite
      prevented HOCl-mediated bacterial killing, inhibition of MPO activity, cellular
      cytotoxicity and inhibition of TNF-alpha production. Nitrite did not affect any
      activity of TauCl. CONCLUSION: We have shown that nitrite may react in vitro with
      HOCl but not with TauCl, to form new biologically active product(s). We did not
      confirm the hypothesis that a product of HOCl reaction with nitrite is more toxic
      than HOCl. To the contrary, we found that nitrite diminished bactericidal and
      immunoregulatory properties of HOCl. In vivo, nitrite will also compete with
      taurine for reaction with PMN-released HOCl. Nevertheless, due to high
      concentration of taurine in PMN cytosol, formation of TauCl will be a major
      regulatory mechanism of MPO-halide-system.

PMID- 10939619
TI  - Comparative quantification of IL-1beta, IL-10, IL-10r, TNFalpha and IL-7 mRNA
      levels in UV-irradiated human skin in vivo.
AB  - OBJECTIVE AND DESIGN: Ultraviolet (UV) exposure induces local immunosuppression
      and inflammation in human skin. Cytokines are, in part, responsible for these
      responses. To investigate the effects of UV-induced gene expression at the
      molecular level we established a sensitive in vivo/ex vivo method for a
      comparative quantification of cytokines and receptors involved in the local skin
      immune reactions. MATERIAL AND METHODS: Specific mRNA levels of human UV
      irradiated skin were determined by real time quantification (TaqMan RT-PCR).
      Highly efficient PCR-reaction conditions were obtained by designing very short
      PCR-templates (72-87 bp). The most sensitive PCR-conditions were obtained by
      optimisation of primer and Mn(OAc)2-concentrations, which led to significant PCR
      signals (C(T)-value) of less than 36 cycles. A strong correlation between PCR
      efficiency of the internal control (GAPDH) compared to targets (IL-1beta, IL-10,
      IL-10r, TNFalpha, IL-7) allowed the use of deltadelta C(T)-method to quantify
      comparable mRNA levels. RESULTS: Interleukin-1beta (IL-1beta), Interleukin-10 (IL
      10), and tumour necrosis factor alpha (TNFalpha) mRNA levels were increased in a
      time- and dose-dependent manner. Interleukin-1beta induction reached a maximum
      (approx. 44-fold) 6 h after a UV-dose equivalent to 3 times the minimal erythemal
      doses just perceptible (MEDjp). Maximal TNFalpha mRNA expression (approx. 14
      fold) was also detected 6 h after UV exposure. Interleukin-10 mRNA induction
      reached a maximum of approximately 14-fold 24 h after UV-irradiation of 3 MEDjp.
      Time- and dose-dependent changes in Interleukin-7 and Interleukin-10 receptor
      mRNA levels did not occur after UV-irradiation. CONCLUSIONS: Time-distinct gene
      induction of IL-1beta, TNFalpha and IL-1beta is involved in UV-induced immune
      reactions, but no considerable changes were found for IL-10r or IL-7.

PMID- 10939620
TI  - Acute inhibition of nitric oxide exacerbates airway hyperresponsiveness,
      eosinophilia and C-C chemokine generation in a murine model of fungal asthma.
AB  - OBJECTIVE AND DESIGN: This study examined the role of nitric oxide in changes in
      airway physiology and inflammation in a murine model of fungal allergy induced by
      Aspergillus fumigatus (A. fumigatus) by treatment of A. fumigatus-sensitized mice
      with NG-nitro-L-arginine methyl ester (L-NAME) or D-NAME (8 mg/kg; i.p.).
      MATERIALS AND METHODS: Female CBA/J mice received A. fumigatus antigen dissolved
      in incomplete Freund's adjuvant (10 mg/100 ml i.p. and s.c.) followed 2 weeks
      later by A. fumigatus antigens (20 mg; i.n.) and a subsequent i.t. challenge 4
      days later. Airway physiology and inflammation were examined (24 to 72 h)
      following i.t. challenge. RESULTS: L-NAME-treated mice had lower lung nitrite
      levels 24 h after A. fumigatus challenge, but higher airway hyperresponsiveness
      and inflammation compared to D-NAME controls. Airway inflammation in the L-NAME
      treatment group (72 h) was characterized by a greater bronchoalveolar lavage
      (BAL), peribronchial eosinophilia and augmented levels of CC chemokines compared
      to controls. CONCLUSIONS: These findings suggest that nitric oxide is an
      important modulator of airway hyperresponsiveness, inflammation and C-C chemokine
      generation during allergic airway responses to A. fumigatus.

PMID- 10939621
TI  - The novel acute phase protein, IHRP, inhibits actin polymerization and
      phagocytosis of polymorphonuclear cells.
AB  - OBJECTIVE AND DESIGN: In the present study, the involvement of the binding of
      IHRP (inter-alpha-trypsin inhibitor family heavy chain-related protein) and actin
      in phagocyte activity was investigated. MATERIALS AND METHODS: The actin
      polymerization and the phagocytic activity of the polymorphonuclear (PMN) cells
      were studied in the presence of IHRP. RESULTS: IHRP inhibited the polymerization
      of actin and the phagocytic activity of the PMN cells. CONCLUSION: 1) IHRP may
      bind to actin released from the damaged cells and suppress its toxic action by
      preventing the formation of actin fibril. 2) IHRP may bind to cell surface actin
      on PMN cells and inhibit their phagocytic activities. 3) From these results, IHRP
      may act as an anti-inflammatory protein.

PMID- 10939622
TI  - Cholangiocarcinoma and liver cirrhosis in relation to changes due to
      thioacetamide.
AB  - Different doses of thioacetamide (0.05%, 0.1% and 0.15%) were used to induce
      liver cirrhosis in Wistar rats. Thioacetamide at 0.5% caused cirrhosis by the
      twelfth week of treatment. A severe bile duct proliferation and
      cholangiocarcinoma was seen at longer intervals. Animals treated with higher
      doses (0.1% and 0.15%) of thioacetamide developed more severe intense
      degenerative changes in the liver and died in the twelfth and eighth week
      respectively. The serum and tissue contents of Zn and Cu changed in a
      characteristic fashion that was consistent with the severity of the liver damage.
      Serum Zn and Cu concentrations were at their lowest in the animals that developed
      severe degenerative liver and died at higher dose (0.15%) of thioacetamide. This
      study indicates that treatment of rats with 0.05% thiocetamide is more effective
      and appropriate for the induction of liver cirrhosis. Continued administration of
      the drug at this dosage led to the development of further changes in the liver.
      This model may be suitable for studying these long term changes that occur in the
      liver and lead to cirrhosis. Events that precede the development of severe bile
      duct proliferation and cholangiocarcinoma may also be studied.

PMID- 10939623
TI  - Expression of receptor protein tyrosine phosphatase alpha mRNA in human prostate
      cancer cell lines.
AB  - Receptor protein tyrosine phosphatase alpha (RPTPalpha) is a transmembrane
      protein phosphatase, and has been proposed to be involved in the differentiation
      of the neuronal system. In the present study, we demonstrated the expression of
      RPTPalpha mRNA in several normal human tissues. We further investigated the
      regulation of expression of RPTPalpha mRNA in epithelial cells utilizing three
      commercially available human prostate cancer cell lines LNCaP, PC-3 and DU145.
      This is because these cells exhibit different levels of differentiation, defined
      by the expression of a tissue-specific differentiation antigen, prostatic acid
      phosphatase (PAcP), and their androgen sensitivity. LNCaP cells express PAcP and
      are androgen-sensitive cells, while PC-3 and DU145 cells do not express PAcP and
      are androgen-insensitive cells. Northern blot analyses revealed that, in LNCaP
      cells, fetal bovine serum (FBS) and 5alpha-dihydrotestosterone (DHT) down
      regulates RPTPalpha mRNA expression, similar to the effect on PAcP. Contrarily,
      FBS up-regulated the RPTPalpha mRNA level in PC-3 and DU145 cells. In LNCaP
      cells, sodium butyrate inhibited cell growth and up-regulated RPTPalpha as well
      as PAcP mRNA expression. Although, sodium butyrate also inhibited the growth of
      PC-3 and DU145 cells, the level of RPTPalpha mRNA was decreased in PC-3, while
      increased in DU145 cells. Thus, data taken together indicate that the expression
      of RPTPalpha is apparently regulated by a similar mechanism to that of PAcP in
      LNCaP cells.

PMID- 10939624
TI  - Vascular response of the rabbit bladder to short term partial outlet obstruction.
AB  - Partial bladder outlet obstruction of the rabbit bladder results in a rapid
      increase in mass characterized by remodeling of the bladder wall. In this study
      we investigated the effect of partial outlet obstruction on microvessel density
      and distribution in the bladder wall immunohistochemically using CD31 as a marker
      for vascular endothelium, and on blood flow using a fluorescent microsphere
      technique. Transverse sections of bladder wall were examined after 0
      (unobstructed), 1, 3, 5, 7, and 14 days of obstruction. The microvasculature of
      obstructed rabbit bladder mucosa and detrusor smooth muscle apparently increased
      relative to augmentation of these compartments, while new vessels appeared in the
      thickening serosa. These vascular changes correlated with results showing that,
      at 1 week after obstruction, blood flow (ml/min/g tissue) to the mucosa and
      detrusor was unchanged. Thickening of the serosa, apparent after 1 day of
      obstruction, began before its vascularization. Then, 1 week post-obstruction,
      there was significant microvessel formation in the transition region between the
      detrusor smooth muscle and the increasing serosa; after 2 weeks, the entire
      serosa was vascularized. The vascularization of the muscle-serosal transition
      region and then the remaining serosa apparently precedes fibroblast
      differentiation, providing blood supply and thus metabolic support for this
      process. All obstructed rabbit bladders in this study were in a state of
      compensated function based on their weights. Our working hypothesis is that blood
      flow per unit tissue mass is normal in compensated obstructed bladders, thus
      allowing for normal contractile function and cellular metabolism. The results of
      this study indicate the presence of an augmented microvasculature in compensated
      obstructed rabbit bladders that provides adequate blood perfusion for normal
      function.

PMID- 10939625
TI  - Regulation of ANP-stimulated guanylate cyclase in the presence of Mn2+ in rat
      lung membranes.
AB  - The catalytic activity of guanylate cyclase (GCase) coupled to atrial natriuretic
      peptide (ANP) receptor depends on the metal co-factor, Mn2+ or Mg2+. ATP
      synergistically stimulates the ANP-stimulated GCase in the presence of Mg2+. We
      have now shown the ATP regulation of the ANP-stimulated GCase in the presence of
      Mn2+ in rat lung membranes. ANP stimulated the GCase 2.1-fold compared to the
      control. ATP enhanced both the basal (basal-GCase) and the ANP-stimulated GCase
      maximally 1.7- and 2.3- fold compared to the control, respectively, at a
      concentration of 0.1 mM. The stimulation by ATP was smaller in the presence of
      Mn2+ than in the presence of Mg2+. The addition of inorganic phosphate to the
      reaction mixture altered the GCase activities in the presence of Mn2+ with or
      without ANP and/or ATP. In the presence of 10 mM phosphate, ATP dose-dependently
      stimulated the basal GCase 5-fold compared to the control at a concentration of 1
      mM and augmented the ANP-stimulated GCase, which was 4.2-fold compared to the
      basal-GCase, 5.5-fold compared to the control at a concentration of 0.5 mM.
      Protein phosphatase inhibitors, okadaic acid (100 nM), H8 (1 microM) and
      staurosporin (1 microM), did not alter the activity. Orthovanadate (1 mM), an
      inorganic phosphate analogue, significantly stimulated both the basal-GCase and
      the ANP-stimulated GCase, which were inhibited by ATP. It was assumed that
      phosphate and orthovanadate might interact with the GCase to regulate the
      activity in the opposite manner. This was the first report that inorganic
      phosphate and orthovanadate affected the ATP-regulation of the ANP-stimulated
      GCase in the presence of Mn2+.

PMID- 10939626
TI  - Human quadriceps muscle mitochondria: a functional characterization.
AB  - Human quadriceps mitochondria were isolated from ca. 80 mg tissue in ca. 45%
      yield. The preparation is described with respect to content of mitochondrial
      markers and nine different respiratory activities. The specific state 3
      activities were high in comparison with literature data, indicating high
      integrity and purity of the preparation. Examples of state 3 rates, in micromol O
      min(-1) g protein(-1) (25 degrees C): pyruvate + malate, 400; succinate, 514;
      malate + glutamate, 444. The notion of high integrity was also supported by the
      reproducibility of the preparation and the magnitude of the respiratory control
      ratios and the P/O ratios. The mitochondria most likely had lost ca. 30% of their
      cytochrome c upon isolation, but it was substantiated that this loss had not
      influenced the state 3 rates. Functional assays of single reactions or groups of
      reactions could be based on respiration experiments. The respiratory chain
      activity, for instance, was measured as respiration of NADH in freeze
      permeabilized mitochondria (1263 micromol O min(-1) g protein(-1)). Comparison of
      uncoupled rates of respiration and state 3 rates indicated that the ATP synthesis
      exerted major flux control over respiration of succinate + glutamate, malate +
      glutamate and pyruvate + malate. These reactions, showing very similar rates of
      ATP synthesis, could be used as a functional assay of ATP synthesis (1200
      micromol ATP min(-1) g protein(-1)). Respiration of succinate, palmitoyl
      carnitine + malate, or glutamate could not support the maximal rate of ATP
      synthesis and the upstream reactions probably exerted major flux control in these
      cases. The specific activities appeared very constant in this group of young men,
      only the respiratory activity with glutamate might show biological variation.

PMID- 10939627
TI  - Secretion of endothelin converting enzyme-1a: the hydrophobic signal anchor
      domain alone is not sufficient to promote membrane localization.
AB  - Endothelin converting enzyme-1 (ECE-1) is a type II membrane protein that is
      important for the proteolytic activation of big endothelin-1 to endothelin-1.
      Although the highly conserved zinc-binding motif is known to be located in the
      extracellular domain, the role(s) of the N-terminal and membrane-spanning signal
      anchor domains in the biosynthesis and function of ECE-1 isoforms, ECE-1a, ECE
      1b, and ECE-1c, remain undetermined. In this study, we provide evidence that the
      deletion of the cytoplasmic N-terminal tail (residues 1-55) of ECE-1a results in
      the cleavage of a potential signal peptide located in the signal anchor domain
      leading to the partial secretion of the recombinant enzyme into the media.
      However, the truncation of N-terminal and/or signal anchor domain does not affect
      the activity of ECE-1a. Therefore, our results demonstrate that the hydrophobic
      signal anchor domain alone is not sufficient for the membrane anchoring of ECE-1a
      and that the N-terminal domain of ECE-1a is important for membrane targeting as
      well as the intracellular localization of the enzyme.

PMID- 10939629
TI  - Exogenous expression of Msx1 renders myoblasts refractory to differentiation into
      myotubes and elicits enhanced biosynthesis of four unique mRNAs.
AB  - Murine myoblast cell lines stably transfected with expression vectors containing
      homeobox Msx1 cDNA in sense (F31-c) or antisense (F3R1) orientation have
      contrasting phenotypes. F3R1 cells readily differentiate in medium containing low
      serum whereas F31-c cells fail to differentiate under these conditions. The
      mechanism by which exogenous overexpression of Msx1 leads to the altered
      phenotype of F31-c cells and the downstream targets of Msx1 are unknown. Using
      the method of differential display, we have identified four cDNAs that represent
      transcripts up-regulated in F31-c. Two of these cDNAs are homologous to ribosomal
      proteins S23 and S24 while the third has homology to sequences in the murine Tcp
      1 gene. A fourth cDNA does not have appreciable homology to cDNA sequences
      deposited in the NIH GenBank. Since withdrawal from the cell cycle and enhanced
      expression of MyoD commonly precede differentiation of myoblasts into myotubes,
      we also examined regulation of the major cell cycle proteins as well as MyoD by
      Western blot analysis. We show that the levels of Cdks 2, 4 and 6, cyclins A and
      D, and the Cdk inhibitor p27 in both proliferating and serum-starved F31-c cells
      were similar to those in F3R1. Finally, although MyoD protein levels increased in
      both cell types after 72 h incubation in serum depleted medium, the levels of
      MyoD in serum-starved F31-c cells were 2-4 fold lower. We postulate that the
      reduced amount of MyoD is sufficient to permit reversible withdrawal of F31-c
      cells from the cell cycle, but is inadequate to permit myogenesis.

PMID- 10939628
TI  - Regulation of endothelin-1 gene expression in human microvascular endothelial
      cells by hypoxia and cobalt: role of hypoxia responsive element.
AB  - Endothelin-1 (Et-1) is a vasoconstrictor peptide that plays an important role in
      the pathophysiology of hypertension, myocardial ischemia, and other diseases. We
      examined the mechanism of regulation the Et-1 mRNA expression in human
      microvascular endothelial cells (HMEC-1) in response to hypoxia and cobalt. To
      determine whether the 5'-flanking region of Et-1 gene mediate transcriptional
      responses to cellular hypoxia, we constructed reporter plasmids in which Et-1 5'
      flanking sequences of Et-1 gene were fused to luciferase coding sequences.
      Constructs, which contain native Et-1 sequence 5'-AACGTGCA-3', located between 
      118 and -125 in the opposite orientation as the transcriptional unit, mediate
      transcriptional response to hypoxia and cobalt. This responsiveness was inhibited
      by genistein, a tyrosine kinase selective inhibitor. Both hypoxia and cobalt
      induced binding of HIF-1 (hypoxia inducible-1 factor) to this Et-1 hypoxia
      responsive element in gel shift assays. Mutation in this sequence eliminated both
      the hypoxia-induced HIF-1 binding and luciferase expression. Using the supershift
      assay we have shown that this hypoxia responsive element binds HIF-1alpha and HIF
      1beta proteins. Interestingly, genistein only slightly affected HIF-1 binding.
      These results indicate that the Et-1 gene contains HIF-1 binding hypoxia
      responsive elements which mediate transcriptional responses to hypoxia and cobalt
      in microvascular endothelial cells. Genistein appears to inhibit this response by
      affecting the transcriptional activity of the HIF-1 complex, without
      significantly affecting its DNA-binding properties.

PMID- 10939630
TI  - Retinol-induced elevation of ornithine decarboxylase activity in cultured rat
      Sertoli cells is attenuated by free radical scavenger and by iron chelator.
AB  - We investigated retinol effects in ornithine decarboxylase activity in Sertoli
      cells. We also tested the hypothesis that free radical scavengers and iron
      chelators may attenuate the effect of retinol. Sertoli cells isolated from 15-day
      old Wistar rats were previously cultured for 48 h and then treated with retinol
      by 24 h with or without mannitol (1 mM) or 1,10 phenanthroline (100 microM). We
      measured ornithine decarboxylase and catalase activities and malondialdehyde
      concentrations in response to retinol treatment. In response to 7 microM retinol
      treatment ornithine decarboxylase activity increased 30%. Retinol-induced
      ornithine decarboxylase activity was significantly decreased by addition of free
      radical scavenger (mannitol) or iron chelator (1,10 phenanthroline). In addition
      the same effect was observed in catalase increased activity and in
      malondialdehyde concentrations. These results suggest that retinol treatment
      induced ornithine decarboxylase and catalase activity and increased
      malondialdehyde concentration. These effects appear to be mediate by ROS.

PMID- 10939631
TI  - Acute modulation of the extent of apoB mRNA editing and the relative rates of
      syntheses of apoB48 and apoB100 in cultured rat hepatocytes by osmotic and other
      stress stimuli.
AB  - The mRNA for apolipoprotein B (apoB) is edited by the enzyme APOBEC-1, which acts
      as part of a multiprotein complex or editosome. In cultured rat hepatocytes
      obtained from fed animals this results in the presence of edited and unedited
      apoB mRNA in a ratio of approximately 3:2 in the basal state. In this study we
      show that hyper-osmotic media, which induce cell shrinkage, resulted in an acute
      increase in the degree of editing of apoB mRNA (hypo-osmotic conditions had no
      effect). This increase was accompanied by a parallel and highly positively
      correlated change in the ratio of the rate of synthesis of apoB48 relative to
      that of apoB100. These changes occurred in the absence of any changes in the
      overall APOBEC-1 mRNA levels, indicating that the activation of editing occurred
      at a post-transcriptional level. Levels of total apoB mRNA were also unaffected
      by hyper-osmotic exposure of the cells indicating that changes in the relative
      rates of synthesis of apoB48 and apoB100 were due to post/translational events.
      Exposure of cells to anisomycin at concentrations (50 micrograms/ml) that inhibit
      protein synthesis or to the transcriptional inhibitor actinomycin D produced
      changes in the degree of apoB mRNA editing that were similar to those given by
      hyper-osmotic shock indicating that editing is able to respond acutely to
      transcriptional or translational inhibition. Anisomycin, at concentrations (50
      ng/ml) that activate SAPK/JNK but do not inhibit protein synthesis, gave only a
      fraction of the effect of hyper-osmotic shock. SB203580, an inhibitor of p38
      kinase, did not attenuate the effects of hyper-osmotic conditions on APOBEC-1
      editing. These observations suggest that these MAPkinase pathways play a
      relatively minor part in the transduction of the osmotic stimulus to the editing
      mechanism. The hyper-osmotically-induced increase in apoB mRNA editing was also
      insensitive to PD98059 and wortmannin (inhibitors of MEK and PI3 kinase,
      respectively). These data provide evidence that apoB mRNA editing is capable of
      acute modulation independently of transcriptional or translational mechanisms and
      suggest that one or more components of the editosome may undergo post
      translational activation.

PMID- 10939632
TI  - Cyclic stretch induces the release of growth promoting factors from cultured
      neonatal cardiomyocytes and cardiac fibroblasts.
AB  - Growth factors and hormones may play an autocrine/paracrine role in mechanical
      stress-induced cardiac hypertrophy. Using an in vitro model of mechanical stress,
      i.e. stretch of cardiomyocytes and cardiac fibroblasts, we tested the involvement
      of growth factors and hormones in this process. We found that conditioned medium
      (CM) derived from 4 h cyclicly (1 Hz) stretched cardiomyocytes increased the rate
      of protein synthesis in static cardiomyocytes by 8 +/- 3%. Moreover, CM derived
      from 2 h stretched fibroblasts increased the rate of protein synthesis in static
      fibroblasts as well as in static cardiomyocytes by 8 +/- 2 and 6 +/- 2%,
      respectively. Analysis of CM using size-exclusion HPLC showed that cardiomyocytes
      and fibroblasts released at least three factors with MW < or = 10 kD, their
      quantities being time-dependently increased by stretch. Subsequent analyses using
      immunoassays revealed that cardiomyocytes released atrial natriuretic peptide
      (ANP) and transforming growth factor-beta1 (TGFbeta1) being increased by 45 +/-
      17 and 21 +/- 4% upon 4 h of stretch, respectively. Fibroblasts released TGFbeta1
      and very low quantity of endothelin-1 (ET-1). The release of TGFbeta1 was
      significantly increased by 18 +/- 4% after 24 h of stretch in fibroblasts. Both
      cell types released no detectable amount of angiotensin II (Ang II). In
      conclusion, upon cyclic stretch cardiomyocytes and fibroblasts secrete growth
      factors and hormones which induce growth responses in cardiomyocytes and
      fibroblasts in an autocrine/paracrine way. TGFbeta secreted by cardiomyocytes and
      fibroblasts, and ANP secreted by cardiomyocytes are likely candidates. We found
      no evidence for the involvement of Ang II and ET-1 in autocrine/paracrine
      mechanisms between cardiac cell types.

PMID- 10939633
TI  - Evolutionary conservation of post-transcriptional 3' end adenylation of small
      RNAs: S. cerevisiae signal recognition particle RNA and U2 small nuclear RNA are
      post-transcriptionally adenylated.
AB  - The 3' terminal nucleotide of several human small RNAs, including Signal
      Recognition Particle (SRP) RNA, 7SK RNA, U2 small nuclear RNA and ribosomal 5S
      RNA was previously characterized and a fraction of these RNAs was found to
      contain a single post-transcriptionally added adenylic acid residue on their 3'
      ends. Here we report the development of a reverse transcription-polymerase chain
      reaction (RT-PCR) assay for determining and quantifying the extent of post
      transcriptional adenylation of RNAs from different species. Using this assay, we
      found that a fraction of S. cerevisiae U2 small nuclear RNA and S. cerevisiae SRP
      RNA contain a post-transcriptionally added adenylic acid residue on their 3'
      ends. Sequencing analysis confirmed this adenylation to be post-transcriptional.
      Corresponding small RNAs in Xenopus oocytes also contained this post
      transcriptional adenylation on their 3' ends. These data show that post
      transcriptional adenylation on the 3' end of several small RNA molecules is
      conserved through evolution. Xenopus SRP RNA from both cytoplasmic and nuclear
      compartments contained post-transcriptionally added adenylic acid residue on its
      3' end. In addition, the Alu portion of SRP RNA was adenylated, when injected
      into the cytoplasm of frog oocytes. These data show that this novel adenylating
      machinery, capable of specifically adding a single adenylic acid to the 3' end of
      some RNA molecules, is present and functional in both nucleus and cytoplasm.

PMID- 10939634
TI  - Properties of the protein kinase that phosphorylates prothymosin alpha.
AB  - The prothymosin alpha kinase (ProTalphaK) is an apparently novel enzyme that is
      responsible for the phosphorylation of prothymosin alpha (ProTalpha), involved in
      the proliferation of mammalian cells. The present study investigated the
      properties of this enzyme. ProTalphaK is more effectively activated by Mn2+ than
      by other divalent cations, and its activity is unaffected by RNA. Its principal
      substrate in proliferating cells appears to be ProTalpha. Both in vivo and in
      vitro, it is unable to phosphorylate the peptides thymosin alphaI and thymosin
      alphaII, derived from the amino terminus of ProTalpha, despite the fact that the
      sites of phosphorylation of ProTalpha are contained within this part of its
      sequence. In trials in vivo, inhibition of gene expression abolished both
      phosphorylation of ProTalpha and ProTalphaK activity. ProTalphaK is located in
      the cytosolic fractions throughout the cell cycle. Its activity, which is
      dependent on cell proliferation, increases markedly during S phase and begins to
      decline as the cell enters G2. Studies of the effects of activators and
      inhibitors of protein kinases involved in signal transduction pathways suggest
      that ProTalphaK is activated by phosphorylation in a mitogen-initiated pathway
      that is dependent on PKC; however, PKC does not itself phosphorylate ProTalphaK,
      which is therefore presumably phosphorylated by another kinase.

PMID- 10939635
TI  - Developmental changes in regulation of mitochondrial respiration by ADP and
      creatine in rat heart in vivo.
AB  - In saponin-skinned muscle fibers from adult rat heart and m. soleus the apparent
      affinity of the mitochondrial oxidative phosphorylation system for ADP (Km = 200
      400 microM) is much lower than in isolated mitochondria (Km = 10-20 microM). This
      suggests a limited permeability of the outer mitochondrial membrane (OMM) to
      adenine nucleotides in slow-twitch muscle cells. We have studied the postnatal
      changes in the affinity of mitochondrial respiration for ADP, in relation to
      morphological alterations and expression of mitochondrial creatine kinase (mi-CK)
      in rat heart in vivo. Analysis of respiration of skinned fibers revealed a
      gradual decrease in the apparent affinity of mitochondria to ADP throughout 6
      weeks post partum that indicates the development of mechanism which increasingly
      limits the access of ADP to mitochondria. The expression of mi-CK started between
      the 1st and 2nd weeks and reached the adult levels after 6 weeks. This process
      was associated with increases in creatine-activated respiration and affinity of
      oxidative phosphorylation to ADP thus reflecting the progressive coupling of mi
      CK to adenine nucleotide translocase. Laser confocal microscopy revealed
      significant changes in rearrangement of mitochondria in cardiac cells: while the
      mitochondria of variable shape and size appeared to be random-clustered in the
      cardiomyocytes of 1 day old rat, they formed a fine network between the
      myofibrils by the age of 3 weeks. These results allow to conclude that in early
      period of development, i.e. within 2-3 weeks, the diffusion of ADP to
      mitochondria becomes progressively restricted, that appears to be related to
      significant structural rearrangements such as formation of the mitochondrial
      network. Later (after 3 weeks) the control shifts to mi-CK, which by coupling to
      adenine nucleotide translocase, allows to maximally activate the processes of
      oxidative phosphorylation despite limited access of ADP through the OMM.

PMID- 10939637
TI  - Sympathetic control of glucagon receptor mRNA levels in brown adipose tissue of
      cold-exposed rats.
AB  - Brown adipose tissue (BAT) is implicated in both cold-induced thermogenesis and
      regulation of energy expenditure and is mainly controlled by sympathetic
      innervation. To clarify the permissive and/or complementary roles of glucagon in
      cold-induced BAT activation, glucagon receptor gene expression and its modulation
      by sympathetic activity were investigated in rats. One pad of interscapular BAT
      was surgically denervated while the other pad was sham operated, then rats were
      either cold-exposed (CE) for 1 week at 4 degrees C or kept near thermoneutrality
      (25 degrees C, TN). Using a semi-quantitative reverse transcriptase-polymerase
      chain reaction (RT-PCR) assay, it was shown that cold exposure decreased (-44%)
      the relative abundance of BAT glucagon receptor mRNA, an effect which was
      prevented by unilateral surgical sympathectomy of BAT. The present results show a
      negative control by sympathetic nervous activity of glucagon receptor gene
      expression and/or of glucagon receptor mRNA stability in BAT of cold-exposed
      rats. The down-regulation of glucagon receptor expression during cold exposure
      does not support a major role of the peptide in the thermogenic control of BAT.

PMID- 10939636
TI  - Liposome associated interferon-alpha-2b functions as an anti-fibrogenic factor in
      dermal wounds in the guinea pig.
AB  - We have previously reported that interferon-alpha-2b (IFN-alpha-2b) can be
      encapsulated in liposomes without compromising its anti-fibrogenic effects on
      dermal fibroblasts in vitro. This study was conducted to determine whether this
      preparation applied topically to guinea pig wounds can affect their healing. The
      rationale for this approach is that systemic administration of IFN-alpha-2b by
      injection for treatment of dermal fibrosis is uncomfortable, requires a large
      quantity of the cytokine and cannot be easily used in children. Liposomes are
      potentially useful vehicles for the topical delivery of drugs. Empty sonicated
      liposome vesicles were mixed with various concentrations of IFN-alpha-2b and then
      dried and rehydrated. An enzyme-linked immunosorbent assay (ELISA) was used to
      determine the efficiency of encapsulation and the stability of the preparation
      under experimental conditions. A total of 36 full thickness skin wounds
      (6/animal, 3 on each side) were made with an 8 mm disposable punch. Each wound on
      the right side received cream (100 mg/wound) containing 3000 units of liposome
      encapsulated IFN-alpha-2b, while wounds on the left side received cream
      containing empty liposomes. There was a significant reduction in rate of
      contraction of wounds treated with IFN-alpha-2b as early as 5 days after
      wounding. This reduction remained significant up to 10 days. Northern analysis,
      used to evaluate the expression of mRNAs for type I and type III collagens in
      response to IFN-alpha-2b showed a marked reduction in abundance of the
      transcripts for the pro-alpha1(I) chain of type 1 collagen on days 11 and 14
      after wounding. Similarly, the level of mRNA for type III procollagen was
      markedly reduced as early as day 7 and remained depressed up to day 14. These
      findings were consistent with results obtained for the total collagen content in
      tissue samples. Cellularity of the IFN-alpha-2b-treated wounds, assessed by
      vimentin content, was also markedly reduced at day 7 and remained depressed up to
      day 14. Liposome associated IFN-alpha-2b applied 5 days after completion of
      epithelialization reduced mRNA for the pro-alpha1(I) chain of type 1 collagen,
      confirming its transepidermal penetration and effectiveness. The activity of
      liposome-associated IFN-alpha-2b in vivo supports the concept of the topical use
      of this anti-fibrogenic agent for treatment of fibroproliferative disorders.

PMID- 10939638
TI  - Glycosylphosphatidylinositol (GPI) hydrolysis by transforming growth factor-beta1
      (TGF-beta1) as a potential early step in the inhibition of epithelial cell
      proliferation.
AB  - Glycosylphosphatidylinositol (GPI) was previously identified in rabbit articular
      chondrocytes as being a precursor of inositolphosphate glycan (IPG), released
      upon (Transforming Growth Factor-beta) (TGF-beta) exposure, and capable of
      mimicking the proliferative effects of the growth factor. Here, using mink lung
      epithelial cells (CCL 64), which are known to be growth-inhibited by TGF-beta, we
      studied the potential role of GPI-derived molecules in the antiproliferative
      effect of TGF-beta1. We first identified an endogenous pool of GPI material and
      three different anionic forms of IPG in epithelial cells pre-labeled with
      [3H]glucosamine. Shortly (8 min) after TGF-beta1 addition, the cells responded by
      a rapid and transient hydrolysis of GPI, accompanied by the release of the most
      anionic form of IPG. This TGF-beta-released IPG, after partial purification, was
      shown to decrease the proliferation of CCL 64 cells. Moreover, anti-IPG
      antibodies reduced the effects of TGF-beta and blocked the effects of partially
      purified IPG. These data strongly suggest that GPI hydrolysis may be an early
      step of the TGF-beta signalling pathway involved in growth inhibition of
      epithelial cells.

PMID- 10939639
TI  - Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT
      diaphorase activity.
AB  - Pretreating mice with schisandrin B (Sch B), a dibenzocyclooctadiene derivative
      isolated from the fruit of Schisandra chinensis, at a daily dose of 1 mmol/kg for
      3 days protected against menadione-induced hepatic oxidative damage in mice, as
      evidenced by decreases in plasma alanine aminotransferase activity (78%) and
      hepatic malondialdehyde level (70%), when compared with the menadione intoxicated
      control. In order to define the biochemical mechanism involved in the
      hepatoprotection afforded by Sch B pretreatment, we examined the activity of DT
      diaphorase (DTD) in hepatocytes isolated from Sch B pretreated rats. Hepatocytes
      isolated from Sch B pretreated (a daily dose of 1 mmol/kg for 3 days) rats showed
      a significant increase (25%) in DTD activity. The increase in DTD activity was
      associated with the enhanced rate of menadione elimination in the hepatocyte
      culture. The ensemble of results suggests that the ability of Sch B pretreatment
      to enhance hepatocellular DTD activity may at least in part be attributed to the
      protection against menadione hepatotoxicity.

PMID- 10939641
TI  - Plasma nitric oxide and iron concentrations in exercised rats are negatively
      correlated.
AB  - The aim of this study was to investigate the effect of strenuous exercise on
      plasma nitric oxide and iron (PI) concentrations in rats. The rats were divided
      into six groups: 3, 6 and 12 months of the exercise (swimming) groups and their
      corresponding controls. At the end of experimental periods, blood samples were
      collected to measure plasma NOx (nitrate and nitrite) and iron concentrations and
      other hematological indices. The correlative analysis of plasma NOx with PI in
      the exercised and the control rats was performed. The results showed that plasma
      NOx concentration was significantly greater and PI lower in the 3, 6, and 12
      months of the exercise groups compared to their sedentary controls (p < 0.01).
      However, the duration of strenuous exercise had no significant effect on plasma
      NOx or PI contents. A negative correlation between plasma NOx and PI levels was
      found in all three exercise groups (r = -0.750, -0.578, and -0.808 and p < 0.01,
      0.05, 0.01 respectively), but not in the sedentary control groups. These results
      imply that strenuous exercise may lead to an increase in plasma NOx concentration
      as well as a low iron level. They also suggest the possibility that the increased
      NO production might be associated with the development of the lower iron status
      in exercise.

PMID- 10939640
TI  - Etoposide stimulates 1,25-dihydroxyvitamin D3 differentiation activity, hormone
      binding and hormone receptor expression in HL-60 human promyelocytic cells.
AB  - The simultaneous administration of the DNA topoisomerase II inhibitor etoposide
      (0.15 mM) and 1,25-dihydroxyvitamin D3 (VD3) (10 nM) synergistically induced the
      differentiation of HL-60 human promyelocytic leukemia cells. Similar results were
      obtained using U-937 human promonocytic cells, or the topoisomerase II inhibitors
      doxorubicin (15 nM) and mitoxantrone (2.5 nM). When sequential treatments were
      used, pre-incubation with VD3 had little effect on the subsequent action of
      etoposide, while pre-incubation with etoposide greatly potentiated the subsequent
      action of VD3. In addition, etoposide treatment stimulated VD3 binding activity
      and increased VD3 receptor mRNA and protein levels. The increase in hormone
      receptor expression may explain, at least in part, the capacity of topoisomerase
      inhibitors to potentiate the differentiation inducing activity of VD3.

PMID- 10939642
TI  - Vanadium and diabetes. What about vanadium toxicity?: A reply.

PMID- 10939643
TI  - Validation of publication of new names and new combinations previously
      effectively published outside the IJSEM.

PMID- 10939644
TI  - Notification that new names and new combinations have appeared in volume 50, part
      3, of the IJSEM.

PMID- 10939645
TI  - Pelczaria aurantia ATCC 49321T (=DSM 12801T) is a strain of Kocuria rosea (Flugge
      1886) Stackebrandt et al. 1995.
AB  - Phylogenetic and chemotaxonomic analyses of Pelczaria aurantia ATCC 49321T (= DSM
      12801T) indicate that this species is very closely related to Kocuria rosea. The
      DNA-DNA reassociation value of 87.1% determined for the type strains of the two
      species supports this finding. The results of phylogenetic analysis of the 16S
      rDNA of a subculture of the original strain of Pelczaria aurantia, deposited at
      the National Institutes of Health, Bethesda, MD, USA, as 'Neisseria aurantia',
      are identical to those for strain ATCC 49321T and indicate that Pelczaria
      aurantia ATCC 49321T is an authentic subculture of the original culture described
      by Poston (1993). On the basis of these findings it is concluded that P. aurantia
      ATCC 49321T and K. rosea DSM 20447T are members of the same taxon. The taxonomic
      consequences of this union are discussed.

PMID- 10939646
TI  - Streptococcus infantarius sp. nov., Streptococcus infantarius subsp. infantarius
      subsp. nov. and Streptococcus infantarius subsp. coli subsp. nov., isolated from
      humans and food.
AB  - Eighteen strains isolated from human specimens or from food products were
      characterized as atypical variants of mannitol-negative Streptococcus bovis. They
      were tested for extended biochemical criteria, ribotyping and DNA-DNA
      hybridization in order to define their taxonomic status. These strains were
      demonstrated to constitute a DNA relatedness group that includes strains of DNA
      group 4 of Farrow et al. (1984). Comparative analysis of 16S rRNA sequences
      demonstrated that these strains represent a new species which belongs to the
      Streptococcus bovis/Streptococcus equinus complex and which has been
      provisionally named S. infantarius by Bouvet et al. (1997). Biotyping and
      ribotyping allowed differentiation of these strains from the aesculin-positive
      strains of S. bovis belonging to the previously described biotypes I, II.1 and
      II.2. The results of the ribotyping and hybridization assays demonstrated the
      presence of two different DNA subgroups within the 18 strains. On the basis of
      these data, the names S. infantarius subsp. infantarius (aesculin-negative for
      five strains out of seven, including the type strain HDP 90056T = NCDO 599T) and
      S. infantarius subsp. coli (aesculin-positive, reference strain HDP 90248 = NCDO
      2620) are proposed as the names for these two subspecies within the S.
      infantarius species.

PMID- 10939647
TI  - Actinoalloteichus cyanogriseus gen. nov., sp. nov.
AB  - Phylogenetic analysis of 'Actinoalloteichus cyanogriseus' based on its 16S rDNA
      sequence confirmed that the organism belongs to the family Pseudonocardiaceae. It
      contains glutamic acid, alanine and meso-diaminopimelic acid as cell wall amino
      acids, and menaquinone 9 (H4). Its taxonomic characteristics differ from those of
      the previously described organisms of the family Pseudonocardiaceae. On the basis
      of these morphological, physiological, chemotaxonomic and phylogenetic analyses,
      a new genus, Actinoalloteichus, is proposed, along with a new species, namely
      Actinoalloteichus cyanogriseus sp. nov. The type strain is A. cyanogriseus IFO
      14455T (= AS 4.1159T = JCM 6095T).

PMID- 10939648
TI  - Thiocapsa litoralis sp. nov., a new purple sulfur bacterium from microbial mats
      from the White Sea.
AB  - A new phototrophic purple sulfur bacterium, isolated from benthic microbial mats
      from the White Sea littoral zone, is described. Individual cells were spherical,
      non-motile and lacked gas vesicles. In pure cultures cells appeared in regular
      platelet-like arrangements of four, eight or sixteen cells. Cell division
      occurred inside a common envelope, surrounded by a thick capsule. Internal
      photosynthetic membranes were of the vesicular type. The colour of cell
      suspensions was pink to rose-red. Bacteriochlorophyll a and carotenoids of the
      spirilloxanthin series were found as photosynthetic pigments. Under anoxic
      conditions in the light, photolithoautotrophic growth occurred with sulfide,
      thiosulfate, sulfite and elemental sulfur as electron donors. Sulfur globules
      were stored as an intermediary oxidation product and were visible microscopically
      inside the cells. In the presence of sulfide and bicarbonate, photomixotrophic
      growth occurred with a number of organic substrates. Sulfate could serve as sole
      assimilatory source of sulfur. Chemolithoautotrophic growth in the dark was
      possible with sulfide and thiosulfate as electron donors. Optimum growth occurred
      in the presence of 1% NaCl, at pH 6.5 and at 30 degrees C. The DNA base
      composition of the type strain, BM5T, was 64.0 mol% G+C. According to 16S rDNA
      sequence information and DNA-DNA hybridization, the new isolate clearly belongs
      to the genus Thiocapsa, but is sufficiently different from other recognized
      Thiocapsa species to be described as a new species of this genus for which the
      name Thiocapsa litoralis sp. nov. is proposed. The type strain is BM5T (= ATCC
      700894).

PMID- 10939649
TI  - Phylogenetic analysis of members of the genus Rickettsia using the gene encoding
      the outer-membrane protein rOmpB (ompB).
AB  - To confirm the phylogenetic analysis previously inferred by comparison of the
      citrate synthase and rOmpA gene sequences (gitA and ompA, respectively), the
      rOmpB gene (ompB) of 24 strains of the genus Rickettsia was amplified and
      sequenced. rOmpB is an outer-membrane protein of high molecular mass, the
      presence of which can be demonstrated in most rickettsiae by immunological cross
      reactivity in Western blots. No PCR amplification was obtained with Rickettsia
      bellii or Rickettsia canadensis. For the other rickettsiae, phylogenetic analysis
      was inferred from the comparison of both the gene and derived protein sequences
      by using parsimony, maximum-likelihood and neighbour-joining methods which gave
      the same organization. All nodes were well supported (>86% bootstrap values),
      except in the cluster including Rickettsia africae strain S and Rickettsia
      parkeri, and this analysis confirmed the previously established phylogeny
      obtained from combining results from gltA and ompA. Based on phylogenetic data,
      the current classification of the genus Rickettsia is inappropriate, specifically
      its division into two groups, typhus and spotted fever. Integration of
      phenotypic, genotypic and phylogenetic data will contribute to the definition of
      a polyphasic taxonomy as has been done for other bacterial genera.

PMID- 10939650
TI  - Polyphasic evidence for the reclassification of Rhodothermus obamensis Sako et
      al. 1996 as a member of the species Rhodothermus marinus Alfredsson et al. 1988.
AB  - DNA-DNA reassociation studies, 16S rRNA gene sequence comparisons and fatty acid
      analysis were used to reassess the taxonomic status of the type strain of
      Rhodothermus obamensis and several strains of the genus Rhodothermus isolated
      from widely distributed shallow marine hot springs. The results show that the
      type strain of R. obamensis, JCM 9785T, has a DNA-DNA reassociation value of 78%
      with the type strain of R. marinus, DSM 4252T. The other strains examined had DNA
      DNA reassociation values that varied between about 68 and 94% with R. marinus.
      The 165 rRNA gene sequence was determined for the type strain of R. obamensis and
      found to share 99.5% similarity with the type strain of R. marinus. The fatty
      acid composition of R. obamensis was slightly different from that of the other
      strains examined, but indicated that this strain is very closely related to the
      other strains examined in this study. On the basis of DNA-DNA reassociation
      values, 16S rRNA gene sequence comparison and fatty acid profiles, it was
      concluded that R. obamensis and R. marinus represent the same species and that
      the name Rhodothermus obamensis should be regarded as a junior synonym of
      Rhodothermus marinus.

PMID- 10939651
TI  - A rapid method for determining the G+C content of bacterial chromosomes by
      monitoring fluorescence intensity during DNA denaturation in a capillary tube.
AB  - A simple and rapid method to determine the G+C content of bacterial chromosomal
      DNA was developed. It involves determination of Tm by a Light Cycler and
      calculation of the G+C content by an empirical formula relating Tm to G+C
      content. Instead of a conventional thermal denaturation method, which monitors
      the increase of absorbance at 260 nm, thermal denaturation was monitored by the
      decrease of fluorescence intensity in the presence of SYBR Green 1. In this
      method, the apparent Tm of DNA was influenced by the concentration of SYBR Green
      1, DNA and salt. In addition, when the G+C content was calculated from a linear
      equation [(mol% G+Cx = mol% G+Cr+1.99(Tmx-Tmr), where x is the unknown organism
      and y is the reference organism], an error value was introduced among strains
      with extremely low or high G+C content. Based upon five standards (G+C contents
      in the range 33-66 mol%), a suitable equation was formulated for the capillary
      method: mol% G+Cx = mol% G+Cr+1.4652(Tmx-Tmr)+0.0063(Tmx2-Tmr2). To determine the
      Tm of organisms within this range of G+C contents, Escherichia coli ATCC 11775T
      was used as a DNA standard and fixed concentrations of SYBR Green 1, sodium
      citrate and DNA were used. The data from 37 bacterial strains indicated that this
      equation behaved well. Because it is rapid and simple, it may prove useful for
      bacterial identification.

PMID- 10939652
TI  - Genomic and phenotypic characterization of Xanthomonas cynarae sp. nov., a new
      species that causes bacterial bract spot of artichoke (Cynara scolymus L.).
AB  - A bacterial disease of artichoke (Cynara scolymus L.) was first observed in 1954
      in Brittany and the Loire Valley, France. This disease causes water-soaked spots
      on bracts and depreciates marketability of the harvest. Ten strains of the
      pathogen causing bacterial spot of artichoke, previously identified as a member
      of the genus Xanthomonas, were characterized and compared with type and pathotype
      strains of the 20 Xanthomonas species using a polyphasic study including both
      phenotypic and genomic methods. The ten strains presented general morphological,
      biochemical and physiological traits and G+C content characteristic of the genus
      Xanthomonas. Sequencing of the 165 rRNA gene confirmed that this bacterium
      belongs to the genus Xanthomonas, and more precisely to the Xanthomonas
      campestris core. DNA-DNA hybridization results showed that the strains that cause
      bacterial spot of artichoke were 92-100% related to the proposed type strain CFBP
      4188T and constituted a discrete DNA homology group that was distinct from the 20
      previously described Xanthomonas species. The results of numerical analysis were
      in accordance with DNA-DNA hybridization data. Strains causing the bacterial
      bract spot of artichoke exhibited consistent determinative biochemical
      characteristics, which distinguished them from the 20 other Xanthomonas species
      previously described. Furthermore, pathogenicity tests allowed specific
      identification of this new phytopathogenic bacterium. Thus, it is concluded that
      this bacterium is a new species belonging to the genus Xanthomonas, for which the
      name Xanthomonas cynarae is proposed. The type strain, CFBP 4188T, has been
      deposited in the Collection Francaise des Bacteries Phytopathogenes (CFBP).

PMID- 10939653
TI  - Lactobacillus acidipiscis sp. nov. and Weissella thailandensis sp. nov., isolated
      from fermented fish in Thailand.
AB  - Eleven strains of homofermentative, rod-shaped lactic acid bacteria and five
      strains of heterofermentative, sphere-shaped lactic acid bacteria were isolated
      from fermented fish (pla-ra and pla-chom) in Thailand. They were identified as
      new species and named Lactobacillus acidipiscis sp. nov. and Weissella
      thailandensis sp. nov., respectively, on the basis of phylogenetic analysis of
      the 16S rRNA gene sequences, DNA relatedness and phenotypic characteristics. The
      type strain of L. acidipiscis is FS60-1T (= PCU 207T = NRIC 0300T = HSCC 1411T =
      JCM 10692T = TISTR 1386T) and the type strain of Weissella thailandensis is FS61
      1T (= PCU 210T = NRIC 0298T = HSCC 1412T = JCM 10695T = TISTR 1384T).

PMID- 10939654
TI  - Nocardia abscessus sp. nov.
AB  - Chemotaxonomic and 16S rRNA gene sequence analyses of four bacterial strains
      isolated from clinical material clearly demonstrated that these bacteria belong
      to the genus Nocardia. DNA-DNA hybridization data as well as the physiological
      characteristics of the isolates indicated that they are closely related and
      belong to a single species that differs from previously described members of the
      genus. The name Nocardia abscessus sp. nov. is proposed for these organisms
      represented by strain IMMIB D-1592T (= DSM 44432T). Strain IMMIB D-1592T exhibits
      56.8 and 60.0% DNA-DNA relatedness to Nocardia asteroides ATCC 19247T and
      Nocardia paucivorans DSM 44386T, respectively.

PMID- 10939655
TI  - Paenibacillus koreensis sp. nov., a new species that produces an iturin-like
      antifungal compound.
AB  - A bacterial strain, YC300T, that produces an iturin-like antifungal antibiotic
      was isolated from compost and identified as member of the genus Paenibacillus.
      Gram reaction of the strain was variable depending upon growth stages and culture
      media. Three different types of colonies were developed on tryptic soy agar. The
      organism was facultatively anaerobic and grew at 50 degrees C. The DNA G+C
      content was 54 mol % and anteiso-C15:0 was the major fatty acid. A 0.9 kb
      fragment was produced by PCR amplification of strain YC300T DNA using primers
      PAEN515F and 1377R. Levels of 16S rDNA similarity between strain YC300T and other
      Paenibacillus species were between 89.8 and 94.8%. Phylogenetically, strain
      YC300T formed a significant monophyletic clade with Paenibacillus validus. It is
      clear from polyphasic evidence that the isolate should be classified as
      Paenibacillus koreensis sp. nov., the type strain of which is YC300T (= KCTC
      2393T, KCCM 40903T).

PMID- 10939656
TI  - Reclassification of Bacillus marismortui as Salibacillus marismortui comb. nov.
AB  - Recently, the features of a group of strains isolated from Dead Sea enrichments
      obtained in 1936 by one of us (B. E. Volcani) were described. They were gram
      positive, moderately halophilic, spore-forming rods, and were placed in a new
      species, Bacillus marismortui. At the same time, the new genus Salibacillus was
      proposed for the halophilic species Bacillus salexigens. B. marismortui and
      Salibacillus salexigens have similar phenotypic characteristics and the same
      peptidoglycan type. Phylogenetic analysis based on 16S rRNA sequence comparisons
      showed that they are sufficiently closely related (96.6% similarity) as to
      warrant placement in the same genus. However, DNA-DNA hybridization experiments
      showed that they constitute two separate species (41% DNA similarity). Therefore
      the reclassification of Bacillus marismortui as Salibacillus marismortui comb.
      nov. is proposed.

PMID- 10939657
TI  - Bacteria of an anaerobic 1,2-dichloropropane-dechlorinating mixed culture are
      phylogenetically related to those of other anaerobic dechlorinating consortia.
AB  - A 16S-rDNA-based molecular study was performed to determine the bacterial
      diversity of an anaerobic, 1,2-dichloropropane-dechlorinating bioreactor
      consortium derived from sediment of the River Saale, Germany. Total community DNA
      was extracted and bacterial 16S rRNA genes were subsequently amplified using
      conserved primers. A clone library was constructed and analysed by sequencing the
      16S rDNA inserts of randomly chosen clones followed by dot blot hybridization
      with labelled polynucleotide probes. The phylogenetic analysis revealed
      significant sequence similarities of several as yet uncultured bacterial species
      in the bioreactor to those found in other reductively dechlorinating freshwater
      consortia. In contrast, no close relationship was obtained with as yet uncultured
      bacteria found in reductively dechlorinating consortia derived from marine
      habitats. One rDNA clone showed >97% sequence similarity to Dehalobacter species,
      known for reductive dechlorination of tri- and tetrachloroethene. These results
      suggest that reductive dechlorination in microbial freshwater habitats depends
      upon a specific bacterial community structure.

PMID- 10939658
TI  - Emendation of Pseudomonas straminea Iizuka and Komagata 1963.
AB  - The description of Pseudomonas straminae lizuka and Komagata 1963 was emended
      with data newly obtained. The spelling of the name of this taxon is also
      corrected as Pseudomonas straminea. Strains that were previously named
      'Pseudomonas ochracea' were identified as P. straminea.

PMID- 10939659
TI  - Staphylococcus fleurettii sp. nov., isolated from goat's milk cheeses.
AB  - A new coagulase-negative and novobiocin-resistant species of the genus
      Staphylococcus, Staphylococcus fleurettii, isolated from raw-milk cheeses, is
      described. This species is differentiated from the other novobiocin-resistant
      staphylococci on the basis of ribotype and intergenic transcribed spacer
      patterns, DNA-DNA reassociation reactions, cell wall composition and phenotypic
      characteristics. S. fleurettii could be distinguished by its oxidase activity, by
      its ability to produce acid aerobically from D-trehalose, D-mannose, D-turanose
      and maltose and by its inability to produce acid from D-cellobiose. The type
      strain of S. fleurettii is CIP 106114T (= DSM 13212T).

PMID- 10939660
TI  - Proposal of Oscillochloridaceae fam. nov. on the basis of a phylogenetic analysis
      of the filamentous anoxygenic phototrophic bacteria, and emended description of
      Oscillochloris and Oscillochloris trichoides in comparison with further new
      isolates.
AB  - The nucleotide sequences of the genes of 16S rRNAs were determined for the type
      strain Oscillochloris trichoides DG-6T and three new strains of Oscillochloris
      like mesophilic filamentous green bacteria. Two major clusters have been found
      within the family Chloroflexaceae by phylogenetic-analysis: one cluster includes
      thermophilic species of Chloroflexus and the second includes mesophilic strains
      of Oscillochloris. The degree of relatedness of these clusters was below an
      intergeneric level, having only 82.5-86.5% of 16S rDNA sequence similarity. These
      phylogenetic data correlate well with the significant physiological, biochemical
      and chemotaxonomical differences between members of both groups. Therefore, the
      Oscillochloris and Chloroflexus clusters should be considered as two separate
      families. The description of the new family, Oscillochloridaceae fam. nov., and
      emended descriptions of the genus Oscillochloris and the species Oscillochloris
      trichoides are presented.

PMID- 10939661
TI  - Acidisphaera rubrifaciens gen. nov., sp. nov., an aerobic bacteriochlorophyll
      containing bacterium isolated from acidic environments.
AB  - Four strains of aerobic, mesophilic, acidophilic bacteria that produced
      bacteriochlorophyll (BChl) a were isolated from acidic hot springs and mine
      drainage. The characteristics of the four isolates were almost identical. The
      isolates were strictly aerobic and chemo-organotrophic. They were gram-negative,
      non-motile cocci and coccobacilli, formed salmon-pink colonies on solidified
      media and produced BChl a and carotenoids only under aerobic growth conditions.
      The cells also produced small amounts of zinc-substituted BChl a when grown in
      the presence of 1 mM zinc sulfate. Anaerobic growth in the light was not found,
      but aerobic growth was stimulated by continuous incandescent illumination. The
      isolates grew in a pH range of 3.5-6.0, with pH optima of 4.5-5.0. A phylogenetic
      analysis based on 16S rDNA sequences showed that the isolates clustered in the
      major acidophilic group of the class Proteobacteria, which includes species of
      the genera Acidiphilium and Rhodopila. The anaerobic phototrophic bacterium
      Rhodopila globiformis was the closest relative to the new isolates (95% level of
      sequence similarity). The G+C content of the genomic DNA of the isolates was 69.1
      69.8 mol%. On the basis of these results, it was concluded that the four isolates
      should be classified into a new genus and a new species, for which the name
      Acidisphaera rubrifaciens is proposed. The type strain is strain HS-AP3T (= JCM
      10600T).

PMID- 10939662
TI  - Actinomyces canis sp. nov., isolated from dogs.
AB  - Three strains of a previously undescribed catalase-positive Actinomyces-like
      bacterium were isolated from dogs. Biochemical testing and PAGE analysis of whole
      cell proteins indicated that the strains were phenotypically highly related to
      each other but different from previously described Actinomyces and
      Arcanobacterium species. Sequencing of 16S rRNA showed that the unknown bacterium
      represents a new subline within a cluster of species which includes Actinomyces
      hyovaginalis, Actinomyces georgiae, Actinomyces meyeri, Actinomyces
      odontolyticus, Actinomyces radingae and Actinomyces turicensis. On the basis of
      phenotypic evidence and 16S rRNA sequence divergence levels (greater than 5% with
      recognized Actinomyces species) it is proposed that the unknown strains from
      canine sources be classified as a new species with the name Actinomyces canis sp.
      nov. The type strain of Actinomyces canis is CCUG 41706T (= CIP 106351T).

PMID- 10939663
TI  - Arthrobacter flavus sp. nov., a psychrophilic bacterium isolated from a pond in
      McMurdo Dry Valley, Antarctica.
AB  - CMS 19YT, a psychrophilic bacterium, was isolated from a cyanobacterial mat
      sample from a pond in Antarctica and was characterized taxonomically. The
      bacterium was aerobic, gram-positive, non-spore-forming, non-motile, exhibited a
      rod-coccus growth cycle and produced a yellow pigment that was insoluble in water
      but soluble in methanol. No growth factors were required and it was able to grow
      between 5 and 30 degrees C, between pH 6 and pH 9 and tolerated up to 11.5% NaCl.
      The cell wall peptidoglycan was Lys-Thr-Ala3 (the A3alpha variant) and the major
      menaquinone was MK-9(H2). The G+C content of the DNA was 64+/-2 mol%. The 16S
      rDNA analysis indicated that CMS 19YT is closely related to group I Arthrobacter
      species and showed highest sequence similarity (97.91%) with Arthrobacter agilis.
      Furthermore, DNA-DNA. hybridization studies also indicated 77% homology between
      CMS 19YT and A. agilis. It differed from A. agilis, however, in that it was
      psychrophilic, non-motile, yellow in colour, exhibited a rod-coccus growth cycle,
      had a higher degree of tolerance to NaCl and was oxidase- and urease-negative and
      lipase-positive. In addition, it had a distinct fatty acid composition compared
      to that of A. agilis: the predominant fatty acids were C15:0, anteiso-C15:0,
      C16:0, iso-C16:0, C17:0, anteiso-C17:0 and C18:0. It is proposed, therefore, that
      CMS 19YT should be placed in the genus Arthrobacter as a new species, i.e.
      Arthrobacter flavus sp. nov. The type strain of A. flavus is CMS 19YT (= MTCC
      3476T).

PMID- 10939664
TI  - Phylogenetic affiliation of the pseudomonads based on 16S rRNA sequence.
AB  - The broad and vague phenotypic definition allowed the genus Pseudomonas to become
      a dumping ground for incompletely characterized polarly flagellated, gram
      negative, rod-shaped, aerobic bacteria, and a large number of species have been
      accommodated in the genus Pseudomonas. The 16S rRNA sequences of 128 valid and
      invalid Pseudomonas species, which included almost valid species of the genus
      Pseudomonas listed in the Approved Lists of Bacterial Names, were obtained:
      sequences of 59 species were determined and those of 69 species were obtained
      from the GenBank/EMBL/DDBJ databases. These sequences were compared with the
      sequences of other species of the Proteobacteria. Fifty-seven valid or invalid
      species including Pseudomonas aeruginosa (type species of the genus Pseudomonas
      Migula 1894) belonged to the genus Pseudomonas (sensu stricto). Seven subclusters
      were formed in the cluster of the genus Pseudomonas (sensu stricto), and the
      resulting clusters conformed well to the rRNA-DNA hybridization study by
      Palleroni (1984). The other species did not belong to the genus Pseudomonas
      (sensu stricto) and were related to other genera, which were placed in four
      subclasses of the Proteobacteria (alpha, beta, gamma and gamma-beta subclasses).
      Twenty-six examined species, which were not included in the cluster of the
      Pseudomonas (sensu stricto) and have not been transferred to other genera as yet,
      are listed alphabetically: 'Pseudomonas abikonensis', Pseudomonas antimicrobica,
      Pseudomonas beijerinckii, Pseudomonas beteli, Pseudomonas boreopolis,
      'Pseudomonas butanovora', Pseudomonas carboxydohydrogena, Pseudomonas cissicola,
      Pseudomonas doudoroffii, Pseudomonas echinoides, Pseudomonas elongata,
      Pseudomonas flectens, Pseudomonas geniculata, Pseudomonas halophila, Pseudomonas
      hibiscicola, Pseudomonas huttiensis, Pseudomonas iners, Pseudomonas lanceolata,
      Pseudomonas lemoignei, Pseudomonas mephitica, Pseudomonas pictorum, Pseudomonas
      saccharophila, Pseudomonas spinosa, Pseudomonas stanier, Pseudomonas syzygii and
      Pseudomonas woodsii. The phylogenetic affiliations of these 26 pseudomonads
      species are shown.

PMID- 10939665
TI  - Anaerovorax odorimutans gen. nov., sp. nov., a putrescine-fermenting, strictly
      anaerobic bacterium.
AB  - The strictly anaerobic, gram-positive, non-spore-forming bacterium strain
      NorPut1T ferments putrescine to acetate, butyrate, molecular hydrogen and
      ammonia. It also utilizes 4-aminobutyrate and 4-hydroxybutyrate as growth
      substrates. Comparative 16S rDNA sequence analysis confirmed a phylogenetic
      affiliation of this strain to the phylum of gram-positive bacteria with low DNA
      G+C content. Together with its closest relative, 'Clostridium aminobutyricum'
      (DSM 2634), and several Eubacterium species, strain NorPut1T represents a well
      defined monophyletic group. Moderate overall 16S rRNA sequence similarities (<
      91%) were found for the NorPut1T/'Clostridium aminobutyricum' pair and several
      Eubacterium species. The type species, Eubacterium limosum, is not a member of
      the group and, together with Eubacterium barkeri and Pseudoramibacter
      alactolyticus, represents a distant phylogentic cluster. Therefore, a new genus,
      Anaerovorax, is proposed as harbouring strain NorPut1T (= DSM 5092T), which is
      described as a new species, i.e. Anaerovorax odorimutans.

PMID- 10939666
TI  - Catenibacterium mitsuokai gen. nov., sp. nov., a gram-positive anaerobic
      bacterium isolated from human faeces.
AB  - Six strains of Eubacterium-like strains from human faeces were characterized by
      biochemical tests and analysis of cell wall peptidoglycan type and 16S rRNA. They
      were members of the Clostridium subphylum and have a specific phylogenetic
      association with Lactobacillus catenaformis and Lactobacillus vitulinus. These
      organisms resembled L. vitulinus in possessing the same A1gamma type of murein,
      but they showed different fermentation end-products. On the basis of a 16S rDNA
      sequence divergence of greater than 8% from L. vitulinus as well as phenotypic
      characteristics, a new genus, Catenibacterium, with one species (Catenibacterium
      mitsuokai), is proposed for six strains. The type strain of C. mitsuokai is JCM
      10609T.

PMID- 10939667
TI  - Thermacetogenium phaeum gen. nov., sp. nov., a strictly anaerobic, thermophilic,
      syntrophic acetate-oxidizing bacterium.
AB  - A novel anaerobic, thermophilic, syntrophic acetate-oxidizing bacterium, strain
      PB(T), was isolated from a thermophilic (55 degrees C) anaerobic methanogenic
      reactor which had been treating kraft-pulp waste water. The bacterium oxidized
      acetate in co-culture with a thermophilic hydrogenotrophic methanogen. Strain
      PB(T), a gram-positive, spore-forming, rod-shaped bacterium grew optimally at 58
      degrees C and pH 6.8. The bacterium grew acetogenically on several alcohols,
      methoxylated aromatics, pyruvate, glycine, cysteine, formate and hydrogen/CO2.
      Strain PB(T) also oxidized acetate with reduction of sulfate or thiosulfate as
      the electron acceptor. The bacterium contained MK-7 as the major quinone. The G+C
      content of the DNA was 53.5 mol%. Comparative 16S rDNA analysis indicated that
      strain PB(T) belongs to the Bacillus-Clostridium subphylum. However, it was
      distant from any known genera or micro-organism. The closest known relative was
      Thermoterrabacterium ferrireducens with 87.4% similarity. The name
      Thermacetogenium phaeum gen. nov., sp. nov. is proposed. The type strain is
      strain PBT (= DSM 12270T).

PMID- 10939668
TI  - Denitrovibrio acetiphilus, a novel genus and species of dissimilatory nitrate
      reducing bacterium isolated from an oil reservoir model column.
AB  - A novel dissimilatory, nitrate-reducing bacterium, designated strain N2460T, was
      isolated from an oil reservoir model column. Strain N2460T is a mesophilic,
      obligately anaerobic, marine, gram-negative bacterium. The cells are vibrio
      shaped and motile by a bipolar flagellum. Strain N2460T reduces nitrate to
      ammonia in a mineral medium supplied by acetate. The presence of a 2-oxoglutarate
      dehydrogenase activity indicates that acetate is oxidized via the citric acid
      cycle. No growth is obtained on formate, higher fatty acids, malate, fumarate,
      benzoate, alcohols, sugar, yeast extract, crude oil, alkanes, proline, hydrogen,
      sulfur or thiosulfate with nitrate as electron acceptor. Oxygen, sulfate,
      thiosulfate and sulfur are not utilized as alternative electron acceptors. Strain
      N2460T grows fermentatively on fumarate, but not on pyruvate. The G+C content of
      the DNA is 42.6 mol%. 16S rRNA gene analysis shows that strain N2460T belongs to
      the Bacteria and that the closest relative is 'Geovibrio ferrireducens' (sequence
      similarity 86.9%). On the basis of phylogenetic as well as phenotypic data, it is
      proposed that strain N2460T represents the type strain of a new genus and
      species, Denitrovibrio acetiphilus gen. nov., sp. nov.

PMID- 10939669
TI  - Haloanaerobium fermentans sp. nov., a strictly anaerobic, fermentative halophile
      isolated from fermented puffer fish ovaries.
AB  - A strain of strictly anaerobic and moderately halophilic bacteria isolated from
      salted puffer fish ovaries was studied phenotypically, genotypically and
      phylogenetically. On the basis of its physiological and morphological
      characteristics, the new isolate is considered to be a member of the genus
      Haloanaerobium. It is a motile, rod-shaped, non-spore-forming, gram-negative,
      obligate anaerobe that grows in the presence of 25% (w/v) NaCl. The optimum salt
      concentration for growth is 10% (w/v). It grows well at 15 and 45 degrees C, but
      not at 10 or 50 degrees C. The optimum temperature for growth is 35 degrees C. It
      grows at pH 6.0-9.0 and the optimum pH for growth is 7.5. It ferments N
      acetylglucosamine, cellobiose, fructose, galactose, D-glucose, lactose, maltose,
      D-mannose, raffinose, D-ribose, sucrose and D-xylose. It ferments D-glucose with
      the production of hydrogen, carbon dioxide, ethanol and organic acids such as
      acetate, formate and lactate. 16S rRNA gene sequence information confirmed the
      phylogenetic position of the new isolate, strain R-9T, as a member of the genus
      Haloanaerobium. DNA-DNA hybridization data revealed that isolate R-9T exhibited
      low levels of reassociation (less than 30%) with previously described
      Haloanaerobium species. Based on these results, the new isolate appears to
      represent a new Haloanaerobium species, for which the name Haloanaerobium
      fermentans sp. nov. is proposed. The type strain is R-9T (= JCM 10494T).

PMID- 10939671
TI  - Polyphasic assignment of an aromatic-degrading Pseudomonas sp., strain DJ77, in
      the genus Sphingomonas as Sphingomonas chungbukensis sp. nov.
AB  - Pseudomonas sp. strain DJ77, which was described as an aromatic-degrading
      bacterium, was investigated to clarify its taxonomic position. Phylogenetic
      analysis based on 16S rDNA sequences indicated that the strain belonged to the
      genus Sphingomonas and formed a monophyletic clade with the type strains of
      Sphingomonas chlorophenolica, Sphingomonas herbicidovorans and Sphingomonas
      yanoikuyae with sequence similarity values of 98.1, 96.1 and 95.6%, respectively.
      Genomic relatedness based on DNA-DNA hybridization of strain DJ77 to these
      strains is 7-14%. Strain DJ77 contained ubiquinone 10 as the main respiratory
      quinone, and the G+C content of DNA was 63 mol%. The organism contained
      octadecenoic acid (67%) as major cellular fatty acid. Strain DJ77 can be readily
      differentiated from representative members of the genus Sphingomonas using a
      battery of biochemical tests. On the basis of polyphasic evidence, it is proposed
      that strain DJ77, previously known as Pseudomonas sp., be reclassified in the
      genus Sphingomonas as Sphingomonas chungbukensis sp. nov. The type strain is
      strain DJ77T (= KCTC 2955T = IMSNU 11152T).

PMID- 10939670
TI  - Utility of internally transcribed 16S-23S rDNA spacer regions for the definition
      of Pseudomonas stutzeri genomovars and other Pseudomonas species.
AB  - Bacteria identified and classified as Pseudomonas stutzeri, on the basis of
      traditional criteria, are recognized to be markedly heterogeneous, such that a
      systematic phenotypic characterization has not been correlated with genotypic
      groupings (i.e. genomovars) based upon DNA-DNA similarities. The internally
      transcribed 16S-23S rDNA spacer (ITS1) regions of P. stutzeri were analysed with
      respect to the ability of these nucleic acid regions to differentiate and
      identify the genomic groups (i.e. genomovars) of P. stutzeri. The ITS1s of 34
      strains of P. stutzeri were amplified by PCR and the PCR product was subjected to
      RFLP analysis, which allowed the differentiation and identification of the
      strains to their respective genomovars. Sequence determination and analysis of
      ITS1s supported further the results obtained by RFLP, i.e. nucleotide signatures
      were identified in strains belonging to different genomovars. The ITS1s of all
      strains of P. stutzeri contained the tandem tRNA(Ile)/tRNA(Ala) genes and did not
      exhibit distinct sequence heterogeneity between different operons of a strain.
      Phylogenetically informative variable sites were located, exclusively, in non
      coding regions. The results of the RFLP and sequence analysis of ITS1s supported
      and correlated with the phylogenetic relationships estimated from 16S rRNA gene
      sequence comparisons and DNA-DNA hybridizations, offering an alternative tool for
      genomovar and species differentiation.

PMID- 10939672
TI  - Characterization of Actinomyces isolates from samples from the human urogenital
      tract: description of Actinomyces urogenitalis sp. nov.
AB  - Three strains of a previously undescribed Actinomyces-like bacterium were
      isolated from human clinical sources (urine, urethra and vaginal secretion).
      Biochemical testing and PAGE analysis of whole-cell proteins indicated that the
      strains were phenotypically homogeneous and distinct from previously described
      Actinomyces and Arcanobacterium species. Comparative 16S rRNA gene sequencing
      studies showed the bacterium to be a hitherto unknown subline within a group of
      Actinomyces species which includes Actinomyces bovis, the type species of the
      genus. Based on phylogenetic and phenotypic evidence it is proposed that the
      unknown bacterium from humans be classified as Actinomyces urogenitalis sp. nov.
      The type strain of Actinomyces urogenitalis is CCUG 38702T (= CIP 106421T).

PMID- 10939673
TI  - Phylogeny of 33 ribosomal and six other proteins encoded in an ancient gene
      cluster that is conserved across prokaryotic genomes: influence of excluding
      poorly alignable sites from analysis.
AB  - Thirty-nine proteins encoded in a large gene cluster that is well-conserved in
      gene content and gene order across 18 sequenced prokaryotic genomes were
      extracted, aligned and subjected to phylogenetic analysis. In individual analyses
      of the alignments, only two probable examples of lateral gene transfer between
      archaea and eubacteria were detected, involving the genes for ribosomal protein
      Rpl23 and adenylate kinase. Amino acid sequences for 35 of the 39 proteins were
      concatenated to yield a data set of 9087 amino acid positions per genome. Many of
      these proteins, 33 of which are ribosomal proteins, are not highly conserved
      across distantly related organisms and thus contain many regions that are
      difficult to align. Phylogenetic analyses were performed with subsets of the
      concatenated data from which the most highly variable sites had been iteratively
      removed, using the number of different amino acids that occur at a given site as
      a criterion of variability. Glycine, which has a strong influence on protein
      structure, tended to be more frequent at the most conserved (least polymorphic)
      sites. With most subsets of the data, the proteins from the cyanobacterium
      Synechocystis tended to branch with their homologues from gram-positive bacteria.
      The results indicate that excluding only a few percentage of poorly alignable
      sites from phylogenetic analysis can have a severe impact upon the phylogeny
      inferred and that bootstrap support for branches can fluctuate substantially,
      depending upon which sites are excluded.

PMID- 10939674
TI  - Use of conventional taxonomy, electrophoretic karyotyping and DNA-DNA
      hybridization for the classification of fermentative apiculate yeasts.
AB  - A taxonomic study was conducted that considered strains of the genera
      Hanseniaspora/Kloeckera held in the Industrial Yeasts Collection (DBVPG) of the
      Dipartimento di Biologia Vegetale of the Universita di Perugia, Italy. Standard
      phenotypic as well as molecular criteria were considered in a effort to revisit
      the classification of these strains, some of which have been in the collection
      for about 50 years. Results of salient physiological tests showed that some of
      the DBVPG and type strains could not be identified by current taxonomic keys.
      Electrophoretic karyotypes were identical for some species, with the type strains
      of the seven accepted species showing only five distinct chromosomal patterns.
      DNA-DNA hybridization analyses, using a non-radioactive dot-blot technique,
      allowed for the distinction of taxa. The taxonomic implications of these results
      are discussed.

PMID- 10939675
TI  - What is the phylogenetic position of Cryptosporidium?
AB  - The phylogenetic position of Cryptosporidium is elusive. Although previous
      studies based solely upon small-subunit (SSU) rRNA sequences suggested that the
      genus was an early emerging lineage among the Apicomplexa, bootstrap support for
      this placement was low. Here, the phylogenetic position of Cryptosporidium has
      been re-evaluated for SSU rRNA, fused SSU/large-subunit (LSU) rRNA and six
      protein sequences using traditional distance-based neighbour-joining, maximum
      parsimony and maximum-likelihood methods of phylogenetic reconstruction as well
      as the new Slow-Fast analysis, which focuses upon the slowly evolving positions
      within sequences and is especially useful if a long-branch attraction (LBA)
      artefact is suspected. All the methods of reconstruction indicated a trend for
      the early emergence of Cryptosporidium at the base of the Apicomplexa and showed
      that an LBA artefact plays no role in this placement. Although the inclusion of
      additional numbers of neither species nor genes has significantly enhanced the
      bootstrap support for this phylogenetic position, recent biochemical, molecular
      and ultrastructural data are congruent with it. Therefore, we favour a working
      hypothesis that this genus constitutes an early emerging branch of the
      Apicomplexa.

PMID- 10939676
TI  - Pichia hawaiiensis sp. nov., occurring in decaying bark of Charpentiera trees in
      the Hawaiian archipelago.
AB  - A description is given for Pichia hawaiiensis sp. nov., a nitrate-utilizing
      member of the genus Pichia E. C. Hansen emend. Kurtzman. Seven strains of the new
      species were isolated during the years 1972, 1973 and 1978 from rotting bark of
      the Hawaiian tree genera Charpentiera, Pisonia and Cheirodendron. P. hawaiiensis
      is heterothallic but appears to occur in nature mainly in the diploid state. Asci
      are deliquescent and produce up to four hat-shaped spores per ascus. Phylogenetic
      analysis of the 600 nucleotide D1/D2 domain of the 26S rDNA showed that P.
      hawaiiensis is most closely related to Pichia populi and Williopsis californica
      (syn. Hansenula californica). The type strain of P. hawaiiensis, isolated on the
      island of Hawaii from the rotting bark of Charpentiera sp. containing insect
      larvae, is strain UCD-FST 72-181T (= ATCC MYA-137T = CBS 8760T = NRRL Y-27270T).

PMID- 10939677
TI  - Suggestions for avoiding on-going confusion from the Bacteriological Code.

PMID- 10939678
TI  - The modern Latin word rhabdus belongs to the feminine gender, inducing necessary
      corrections according to Rules 65(2), 12c(1) and 13b of the Bacteriological Code
      (1990 Revision).
AB  - The modern Latin word rhabdus does belong to the feminine gender. According to
      Rules 65(2), 12c(1) and 13b of the Bacteriological Code (1990 Revision), the
      gender of six generic names and the spelling of nine specific and subspecific
      epithets are proposed to be corrected.

PMID- 10939679
TI  - Arguments against the replacement of type species of the genus Salmonella from
      Salmonella choleraesuis to 'Salmonella enterica' and the creation of the term
      'neotype species', and for conservation of Salmonella choleraesuis.
AB  - The proposals of Le Minor and Popoff in 1987 and again of Euzeby in 1999 on the
      type species of the genus Salmonella are in violation of Rule 20a of the
      Bacteriological Code (1990 Revision) and should be rejected. The introduction of
      the term 'neotype species' should be rejected. The specific epithet choleraesuis
      in the binary combination Salmonella choleraesuis should be conserved. The
      serovar name Choleraesuis should be changed to Hogcholera.

PMID- 10939680
TI  - The status of the genus Pelczaria (Poston 1994) and the species Pelczaria
      aurantia (Poston 1994). Request for an Opinion.
AB  - Based upon the results of another publication [P. Schumann et al. (2000). Int J
      Syst Evol Microbiol 50, 1421-1424) it is concluded that the culture Pelczaria
      aurantia ATCC 49321T (= DSM 12801T) currently being distributed does not conform
      to the description of the type strain of Pelczaria aurantia (Poston 1994) and the
      type species of the genus Pelczaria (Poston 1994). It is proposed that the
      Judicial Commission consider (1) that the organism currently deposited as ATCC
      49321T and DSM 12801T be recognized as a member of the species Kocuria rosea; (2)
      that the organism deposited as ATCC 49321T and DSM 12801T as the type strain of
      the species does not represent a strain of the species Pelczaria aurantia; (3) to
      place the name Pelczaria aurantia (Poston 1994) on the list of rejected names if
      a suitable replacement strain, or a neotype, cannot be found within 2 years of
      publication of this Request (Rule 18c); (4) to place the genus name Pelczaria
      (Poston 1994) on the list of rejected names [c.f. Recommendation 20d (3)] if a
      suitable replacement type strain or a neotype for the type species of the genus
      Pelczaria (Poston 1994) cannot be found as outlined in (3).

PMID- 10939682
TI  - Effects of adaptation of vestibulo-ocular reflex function on manual target
      localization.
AB  - The goal of the present study was to determine if adaptive modulation of
      vestibulo-ocular reflex (VOR) function is associated with commensurate
      alterations in manual target localization. To measure the effects of adapted VOR
      on manual responses we developed the Vestibular-Contingent Pointing Test (VCP).
      In the VCP test, subjects pointed to a remembered target following passive whole
      body rotation in the dark. In the first experiment, subjects performed VCP before
      and after wearing 0.5X minifying lenses that adaptively attenuate horizontal VOR
      gain. Results showed that adaptive reduction in horizontal VOR gain was
      accompanied by a commensurate change in VCP performance. In the second
      experiment, bilaterally labyrinthine deficient (LD) subjects were tested to
      confirm that vestibular cues were central to the spatial coding of both eye and
      hand movements during VCP. LD subjects performed significantly worse than normal
      subjects. These results demonstrate that adaptive change in VOR can lead to
      alterations in manual target localization.

PMID- 10939681
TI  - Coordination of a step with a reach.
AB  - Although natural reaching behavior can easily include forward body movement, most
      laboratory studies of reaching have constrained the body to be stationary.
      Recently, however, it has been shown that normal subjects exhibit a different
      pattern of errors when attempting to pinpoint remembered target locations,
      depending on whether or not the reach includes a step. In the study of Flanders
      et al., these errors appeared to be due to the strategy of eye/head/hand
      coordination which normally comes into play when the body is moving toward the
      target. Since the spatial positioning of the head was found to partially explain
      the errors in hand placement, the present study examined the movements of
      patients with bilateral vestibular deficits in order to further analyze the whole
      body coordination. Somewhat surprisingly, the patients exhibited the same pattern
      of head movement and the same errors in hand placement as did the control
      subjects. Nevertheless, the patients' movements clearly exhibited evidence for an
      abnormal decomposition of elbow extension and trunk rotation. Furthermore the
      patients' (spatial) hand paths were significantly more curved than those of
      control subjects and, only in the patients, paths to remembered targets were
      significantly more curved than paths to visible targets. Thus for movements to
      remembered targets, the patients tended to move the hand to the same incorrect
      spatial positions as control subjects but spatiotemporal aspects of the arm and
      body movement differed. The results are consistent with the idea that vestibular
      patients are overly dependent upon visual cues, and support the hypothesis that
      this stepping and reaching behavior is largely dependent upon a visual reference
      signal.

PMID- 10939683
TI  - The effects of scopolamine and cyclizine on visual-vestibular interaction in
      humans.
AB  - The aim of the present study was to investigate the effects of scopolamine (1.5
      mg, transdermal patch) and cyclizine (50 mg tablet), at the doses usually used
      for the relief of motion sickness, on postural sway, optokinetic nystagmus (OKN)
      and circularvection (CV) in humans, using a within-subjects, double-blind,
      placebo-controlled design. Scopolamine and cyclizine were found to have no
      significant suppressive effect on these aspects of visual-vestibular interaction.
      Postural sway and CV were not significantly affected by either drug treatment;
      OKN SPV was significantly increased (p < 0.05), although OKN amplitude and
      frequency were unaffected. These results suggest that scopolamine and cyclizine,
      at doses used for the relief of motion sickness, may have minimal suppressive
      effects on these aspects of visual-vestibular interaction.

PMID- 10939684
TI  - Directional preponderance in pitch circular vection.
AB  - We used optokinetic stimulation (OKS) in eighteen normal adults aged 18-30 years
      to investigate vertical self-motion perception. In order to induce self-rotation,
      either a stripe pattern or a random dot pattern was projected onto the inner wall
      of a hemispherical dome with a diameter of 150 cm. The pattern was rotated either
      about the subject's vertical axis (yaw) or about the subject's interaural axis
      (pitch) for 80 s at a constant acceleration of 1 deg/s2. Stimuli were randomly
      repeated three to four times in each direction. The latency of onset as well as
      the perceived intensity of circular vection (CV) was measured for each stimulus
      presentation. CV latencies for upward rotational stimulation were significantly
      longer than those for downward rotational stimulation under both types of
      stimulus conditions. There was no significant difference in CV latency between
      rightward and leftward rotational stimulation. For most subjects, the magnitudes
      of the perceived CV for rightward rotational stimulation were equal to those for
      leftward rotational stimulation, whereas the magnitudes of the perceived CV for
      vertical stimulation showed large intersubject variability. These results provide
      additional evidence that fundamental differences exist between different types of
      self-motion. Possible explanations for the directional asymmetry in vertical
      perception of self-motion will also be discussed.

PMID- 10939685
TI  - The dynamic gait index relates to self-reported fall history in individuals with
      vestibular dysfunction.
AB  - The purpose of this study was to determine the relationship between gait
      instability and falls history in people with vestibular disorders. A total of 247
      people (164 women, 83 men) participated in the study (mean age = 62.5). Falls
      history within the last 6 months and scores on the Dynamic Gait Index (DGI) were
      compared using the Mantel-Hantzel Chi-square statistic. Thirty-seven percent of
      all subjects reported falling within the last 6 months. Odds ratios in favor of
      falls with DGI scores of 19 or lower was 2.58 (95% C.I. 1.47-4.53). Subjects with
      DGI scores of 19/24 or less were 2.58 times more likely to have reported a fall
      in the previous 6 months than subjects with scores above 19. Younger subjects
      (those under 65 years of age) with vestibular disorders reported more falls than
      persons 65 years of age or over. Younger people may be more willing to risk a
      fall while actively having a vestibular disorder. The DGI appears to be a good
      indicator of fall status in persons with vestibular disorders, regardless of age.

PMID- 10939687
TI  - Torsional dynamics and cross-coupling in the human vestibulo-ocular reflex during
      active head rotation.
AB  - Six subjects fixated an imagined space-fixed target in darkness, or a visible
      target against a structured visual background, while rotating their heads
      actively in yaw, pitch and roll at four different frequencies, from 0.3 to 2.4
      Hz. We used search coils to measure the 3-dimensional rotations of the head and
      eye, and described the relation between them--the input-output function of the
      rotational vestibulo-ocular reflex (VOR)--using gain matrices. We found
      consistent cross-coupling in which torsional head rotation evoked horizontal eye
      rotation. The reason may be that the eyes are above the axis of torsional head
      rotation, and therefore may translate horizontally during the head motion, so the
      VOR rotates them horizontally to compensate. Torsional gain was lower than
      horizontal or vertical, more variable from subject to subject and decreased at
      low frequencies. One reason for the low gain may be that torsional head rotation
      produces little retinal slip near the fovea; hence little compensatory eye motion
      is needed, and so the VOR reduces its torsional gain to save energy or to
      approximate Listing's law by keeping ocular torsion near zero. In addition, the
      human VOR has little experience with purely torsional head rotations and so its
      adaptive networks may be poorly trained for such stimuli. The drop in torsional
      gain at low frequencies can be explained based on the leak in the neural
      integrator that helps convert torsional eye-velocity commands into eye-position
      commands.

PMID- 10939686
TI  - Comparison of protein kinase activity and protein phosphorylation in the medial
      vestibular nucleus and prepositus hypoglossi in labyrinthine-intact and
      labyrinthectomized guinea pigs.
AB  - The aim of the present study was to compare in vitro protein expression, protein
      kinase activity and protein phosphorylation in the medial vestibular nucleus
      (MVN) and prepositus hypoglossi (PH) from labyrinthine-intact guinea pigs and
      from guinea pigs at various stages of vestibular compensation following
      unilateral labyrinthectomy (UL). The ipsilateral (I-MVN) and contralateral (C
      MVN) MVN, and the ipsilateral (I-PH) and contralateral (C-PH) PH, were dissected
      from 3 naive labyrinthine-intact guinea pigs and 55 guinea pigs at 10 hs or 53 hs
      following a surgical UL or sham operation. Tissue extracts were incubated with
      [gamma-33P]ATP+/-Ca2+, phorbol 12, 13 dibutyrate and phosphatidylserine or +/-
      Ca2+ and calmodulin, to enhance protein kinase C (PKC) or calcium calmodulin
      kinase (CaMK) activity, respectively. Data were analysed as the ratio of
      activated to basal 33P incorporation detected by phosphorimaging. There were
      similar total protein and phosphoprotein profiles in the MVN and PH, as well as
      both PKC and CaMKII activity, suggesting that the MVN and PH are similar in the
      way that proteins undergo rapid modification by phosphorylation. During the
      development of vestibular compensation, a 46 kDa band in C-PH displayed higher
      PKC-mediated phosphorylation from 10 hs post-UL compared to sham controls.
      Significantly greater PKC-mediated phosphorylation of proteins of approximately
      18, 46 and 75 kDa was observed in C-PH at 10 hs compared to 53 hs post-UL and in
      most cases the phosphorylation was greater in C-PH than in the C-MVN. These
      results suggest that between 10 and 53 hs post-UL, PKC-mediated phosphorylation
      changes mainly in the C-PH rather than the ipsilateral or contralateral MVN.

PMID- 10939688
TI  - How to reduce the persistent shortage of organ donors in Scandinavia.

PMID- 10939689
TI  - Anaphylactic reactions during induction of anaesthesia using rocuronium for
      muscle relaxation: a report including 3 cases.
AB  - Anaphylaxis during induction of anaesthesia is a dreaded complication with a
      mortality rate of 3-6%, most frequently associated with the use of muscle
      relaxants. Current knowledge on this matter is reviewed in relation to the
      presentation of 3 cases of anaphylaxis and bronchospasm associated with the use
      of the recently released nondepolarizing muscle relaxant rocuronium. Bronchospasm
      may be the sole sign of a serious drug reaction, triggered by precipitation of
      insoluble thiopental crystals when mixed with a muscle relaxant in the
      intravenous (iv) line. It is recommended that these drugs are administered via
      different injection ports. The hypotension requires immediate treatment with
      oxygen, epinephrine and large amounts of iv fluids. Epinephrine infusion may be
      needed for hours. It is recommended that serum tryptase is measured approximately
      2 h after debut of the serious drug reaction. Allergy testing should be performed
      for all the drugs the patient was exposed to, 4-8 weeks after the incident, and
      due to cross-reactivity, including all available muscle relaxants. Doctors are
      urged to inform their patients, and systematically register adverse drug
      reactions.

PMID- 10939690
TI  - Risk factors for postoperative anxiety in children.
AB  - BACKGROUND: Anxiety is defined as a set of behavioural manifestations that can be
      divided into state- and trait-anxiety. State-anxiety is a transitory emotional
      condition that varies in intensity and fluctuates over time. Trait-anxiety is a
      personality trait which remains relatively stable over time. The objective of
      this study was to identify and quantify perioperative risk factors for immediate
      postoperative anxiety in children. METHODS: A prospective cohort study was
      performed with 90 schoolchildren, ages ranging from 7 to 13 years old, ASA
      physical status I-II, submitted to elective surgery. The measuring instruments
      were verbal scale of pain, visual analogue scale (VAS), Trait-State Anxiety
      Inventory for Children (STAIC), Trait-State Anxiety Inventory (STAI) for parents,
      and structured questionnaire. RESULTS: Patients not submitted to analgesic block
      and patients with moderate and intense pain presented an estimated risk 5- and 13
      fold greater for high levels of postoperative state-anxiety, respectively. High
      levels of preoperative state-anxiety and administration of doses of midazolam
      less than 0.056 mg x kg(-1) constituted an estimated risk for postoperative state
      anxiety of 3- and 4-fold, respectively. A positive history of previous surgery
      was associated with lower risk for postoperative anxiety. CONCLUSIONS: High
      levels of preoperative state-anxiety, administration of less than 0.056 mg x kg(
      1) of midazolam, absence of analgesic block and presence of moderate and intense
      postoperative pain constituted risk factors for immediate postoperative state
      anxiety in children. Previous surgery reduced the risk for postoperative anxiety.

PMID- 10939691
TI  - A comparison of anaesthesia using remifentanil combined with either isoflurane,
      enflurane or propofol in patients undergoing gynaecological laparoscopy, varicose
      vein or arthroscopic surgery.
AB  - BACKGROUND: Anaesthesia comprising remifentanil plus isoflurane, enflurane or
      propofol was randomly evaluated in 285, 285 and 284 patients, respectively,
      undergoing short-procedure surgery. METHODS: Anaesthesia was induced with
      propofol (0.5 mg x kg(-1) and 10 mg x 10 s(-1)), and a remifentanil bolus (1
      microg x kg(-1)) and infusion at 0.5 microg x g(-1) x min(-1). Five minutes after
      intubation, remifentanil infusion was halved and 0.5 MAC of isoflurane or
      enflurane, or propofol at 100 microg x kg(-1) x min(-1) were started and titrated
      for maintenance. RESULTS: Patient demography and anaesthesia duration were
      similar between the groups. Surgery was performed as daycases (52%) or inpatients
      (48%). The median times (5-7 min) to extubation and postoperative recovery were
      similar between the groups. Responses to tracheal intubation (15% vs 8%) and skin
      incision (13% vs 7%) were significantly greater in the total intravenous
      anaesthesia (TIVA) group (P<0.05). Fewer patients given remifentanil and
      isoflurane (21%) or enflurane (19%) experienced > or =1 intraoperative stress
      response compared to the TIVA group (28%) (P<0.05). Median times to qualification
      for and actual recovery room discharge were 0.5-0.6 h and 1.1-1.2 h,
      respectively. The most common remifentanil-related symptoms were muscle rigidity
      (6-7%) at induction, hypotension (3-5%) and bradycardia (1-4%) intraoperatively
      and, shivering (6-7%), nausea and vomiting postoperatively. Nausea (7%) and
      vomiting (3%) were significantly lower with TIVA compared with inhaled
      anaesthetic groups (14-15% and 6-8%, respectively; P<0.05). CONCLUSION:
      Anaesthesia combining remifentanil with volatile hypnotics or TIVA with propofol
      was effective and well tolerated. Times of extubation, postanaesthesia recovery
      and recovery room discharge were rapid, consistent and similar for all three
      regimens.

PMID- 10939692
TI  - The effect of two low-dose propofol infusions on the relationship between six
      pulse transcranial electrical stimulation and the evoked lower extremity muscle
      response.
AB  - BACKGROUND: Transcranial stimulation of the motor cortex using high-voltage
      electrical stimuli given in train is a method of monitoring the integrity of the
      motor pathways during thoracoabdominal aortic aneurysm surgery. The purpose of
      this study was to assess the relationship between the stimulus intensity and the
      corresponding amplitude of the myogenic motor evoked potential (tcMEP) in
      response to six-pulse transcranial electrical stimulation during two levels of
      low-dose propofol infusion and stable fentanyl/nitrous oxide anaesthesia.
      METHODS: Nine patients (37-78 yr) scheduled to undergo surgery on the
      thoracoabdominal aorta were studied. After achieving a stable anaesthetic state
      the output voltage was decreased with 50 V intervals from 350 V to 200 V during a
      target propofol infusion aimed at a plasma steady-state concentration of 0.7
      microg x ml(-1) and increased with 50 V intervals from 200 V to 450 V during a
      target propofol infusion aimed at a plasma steady-state concentration of 1.4
      microg x ml(-1). TcMEPs were recorded from the right tibialis anterior muscle.
      RESULTS: Doubling the target propofol infusion to 1.4 microg x ml(-1) resulted in
      a 30-50% decrease in tcMEP amplitude. The largest tcMEP amplitude using the six
      pulse paradigm was found during a propofol infusion aimed at a plasma
      concentration of 0.7 microg x ml(-1) and demanded a stimulus output of 350 V,
      corresponding to a charge density of 7.5 microC x cm(-2) per phase. CONCLUSION:
      Doubling the target propofol infusion to 1.4 microg x ml(-1) provides less
      robust, but still recordable tcMEPs in response to six-pulse electrical
      stimulation. Safety guidelines are discussed.

PMID- 10939693
TI  - Occupational exposure to inhaled anaesthetics: a follow-up study on anaesthetists
      of an eastern European university hospital.
AB  - BACKGROUND: Although no dose-response relationship for the health risks
      associated with the occupational exposure to inhaled anaesthetics exists, public
      health authorities recommend threshold values. The aim of the present study was
      to assess if and to what extent these threshold values are exceeded in an eastern
      European university hospital before and after measures had been taken to reduce
      occupational exposure. METHODS: At nine workplaces occupational exposure of
      anaesthetists to nitrous oxide and halothane or isoflurane was measured by means
      of photoacoustic infrared spectrometry. The measurements were carried out in 1996
      and were repeated in 1997 after the installation of active scavenging devices at
      five workplaces and an air-conditioning system at one workplace. RESULTS:
      Occupational exposure to nitrous oxide and halothane or isoflurane was lower in
      1997 compared to 1996. In 1997 most of the nitrous oxide values still exceeded
      the threshold value of 100 ppm, whereas most of the halothane and isoflurane
      values were already below the threshold values of 5 ppm and 10 ppm in 1996.
      CONCLUSION: The measures taken were effective in reducing waste gas exposure.
      Nevertheless, further efforts are necessary, especially for nitrous oxide, to
      reach western European standards. These efforts comprise structural measures such
      as active scavenging devices and air-conditioning systems at all workplaces, the
      use of total intravenous anaesthesia, low-flow anaesthesia and an appropriate
      working technique.

PMID- 10939695
TI  - Anaesthesia for patients with a transplanted organ.
AB  - Increasing numbers of individuals leading normal lives have transplanted organs.
      They may appear in any hospital for treatment of trauma or general diseases.
      Common anaesthesia methods can be used for these patients, but safe conduct of
      anaesthesia requires knowledge of the immunosuppression, risk factors, and
      altered physiology or drug actions. This article reviews the anaesthesia-related
      literature on patients with transplanted organs.

PMID- 10939694
TI  - Effects on the bispectral index during medium-high dose fentanyl induction with
      or without propofol supplement.
AB  - BACKGROUND: The search for a drug-independent monitor to determine depth of
      anaesthesia and hypnosis continues. The bispectral analysis (BIS) of the EEG
      correlates well with the clinical dose-response of hypnotic drugs during
      induction, but the effect on BIS of an opiate induction, as for coronary bypass
      surgery, is not known. METHODS: Fourteen patients scheduled for elective coronary
      bypass surgery were studied. BIS was recorded during induction in 7 patients
      receiving 10 microg/kg fentanyl without any hypnotic agent and in 7 patients
      receiving 0.5 mg/kg propofol before the fentanyl dose. RESULTS: The effect of
      fentanyl was very variable both regarding BIS and clinical response. Five of the
      7 patients that received only fentanyl lost their response to verbal command
      within 8 min. BIS values at loss of response varied between 45 and 94. One
      patient remained awake with BIS 43. All 7 patients receiving propofol before the
      fentanyl dose lost their response to verbal command within 5 min. BIS values at
      the time for loss of response varied between 78 and 98. CONCLUSION: Loss of
      response to verbal command when a medium-high dose of fentanyl is used for
      induction cannot be distinguished from wakefulness with adequate sensitivity by
      BIS. The current BIS algorithm seems not to accurately reflect the hypnotic
      effects of fentanyl.

PMID- 10939696
TI  - Effects of carbon dioxide pneumoperitoneum for laparoscopic cholecystectomy.

PMID- 10939697
TI  - Changes in the impact factor of anesthesia/critical care journals within the past
      10 years.
AB  - BACKGROUND: The impact factor (IF) is published by the Institute for Scientific
      Information (ISI). There is a tendency to assess quality of scientific journals
      with the help of the IE An analysis of the changes in the IF over time in the
      different specialities may help to further enlighten the worth and problems of
      the IE METHODS: The IFs listed under the subheadings Anesthesiology and Emergency
      Medicine & Critical Care in the Science Citation Index - Journal Citation Report
      were descriptively analysed over the past 10 years. Additionally, IFs of some
      other important journals (subheadings Surgery, Cardiovascular, General Medicine)
      were analysed. RESULTS: The IF of most of the journals showed a constant increase
      over the years (average in Anesthesiology: +65%; average in Emergency Medicine &
      Critical Care: +145%). IFs of the highest ranked journals of other specialities
      showed a similar increase over the years (average in surgical journals: +56%;
      average in cardiac journals: +59%; average in general journals: +40%). More
      Anesthesiology and Emergency Medicine & Critical Care journals originated from
      the USA show an IF >2.0 over the past 10 years than do European journals.
      CONCLUSION: Although the value of the IF is highly controversial, it is a
      frequently used tool to assess rating of a medical journal. Anesthesiology and
      Emergency Medicine & Critical Care journals showed a continuous increase in the
      IF over the past 10 years.

PMID- 10939698
TI  - Gastro-intestinal complement activation during human liver transplantation:
      impact on postoperative liver function.
AB  - BACKGROUND: Liver transplantation elicits a systemic inflammatory response and
      eventually a multiple organ failure syndrome. Gastro-intestinal inflammatory
      activation with release of proinflammatory cytokines and complement activation
      may occur. This study evaluates gastro-intestinal complement activation and the
      association with postoperative parenchymatous liver cell injury and liver
      dysfunction. METHODS: In 17 patients undergoing liver transplantation, blood
      samples were collected from radial artery and portal vein for analysis of
      complement SC5b-9 and endotoxin concentration. Portal venous-arterial SC5b-9
      plasma concentration gradients at 30 min after reperfusion were calculated.
      Outcome parameters included postoperative organ failure and serum concentrations
      of aspartate aminotransferase, alanine aminotransferase, bilirubin and factor II
      VII-X. RESULTS: Patients with gastro-intestinal SC5b-9 release (n=7) had higher
      postoperative serum aspartate aminotransferase and alanine aminotransferase
      concentrations [49 (32-80) microkat/l vs 8 (6-14) microkat/l, P<0.01 and 33 (15
      54) microkat/l vs 8 (4-23) microkat/l, P<0.04, respectively] and lower factor II
      VII-X concentrations [46 (21-48)% vs 60 (47-69)%, P<0.02] compared to patients
      without gastro-intestinal SC5b-9 release (n=10). The ICU stay was prolonged in
      patients with gastro-intestinal complement release. There was no difference in
      number of organ failures and serum bilirubin concentration between the groups.
      The endotoxin concentration in arterial and portal vein blood was low and the
      association between endotoxaemia and complement activation was poor. CONCLUSION:
      Gastro-intestinal complement activation may contribute to postoperative
      parenchymatous liver cell injury and liver dysfunction in patients undergoing
      liver transplantation.

PMID- 10939699
TI  - Effects of dopexamine and volume loading on hemodynamics and oxygenation
      parameters in patients undergoing pulmonary resection.
AB  - BACKGROUND: Pulmonary resection may result in a reduction in arterial oxygen
      pressure as well as in cardiac output. Since cardiac index, oxygen delivery, and
      oxygen consumption are considered as important determinants of patients' outcome,
      we evaluated the effects of dopexamine and volume loading on cardiopulmonary
      variables in patients undergoing pulmonary resection. METHODS: Forty adult
      patients undergoing pulmonary resection for lung or bronchial tumors were
      included in an open placebo-controlled study. The patients were selected
      according to a randomized sequence to group A (n=20) or group B (n=20).
      Dopexamine (2 microg x kg(-1) x min(-1)) was started when steady state conditions
      were achieved after induction of anesthesia in group A. Saline 0.9% was given as
      control (group B). Hemodynamic monitoring was performed using a pulmonary artery
      catheter. RESULTS: Dopexamine increased heart rate, cardiac output and oxygen
      delivery compared with control without increasing oxygen consumption during
      anesthesia and surgery. Furthermore, dopexamine was found not to alter the course
      of PaO2/FiO2 values. CONCLUSION: In patients undergoing pulmonary resection,
      dopexamine can be used perioperatively to increase cardiac index without
      decreasing the PaO2/FiO2 ratio.

PMID- 10939700
TI  - Stability of an epidural analgesic solution containing adrenaline, bupivacaine
      and fentanyl.
AB  - BACKGROUND: A low dose solution of adrenaline 2 microg x ml(-1), fentanyl 2
      microg x ml(-1) and bupivacaine 1 mg x ml(-1) has been reported to give superior
      pain control when used for epidural analgesia after major surgery. The present
      paper describes the compounding and chemical stability of this triple-component
      solution during storage and use. METHODS: Sterile triple-component concentrates
      (11X) were diluted by the use of gas isolator technology to give ready-to-use
      infusion solutions. Eight solutions were analysed by reverse phase high
      performance liquid chromatography (HPLC) methods, and assays were performed on 1,
      45, 90 and 180 days after storage at 2-8 degrees C. After 180 days the solutions
      were subsequently stored at 22 degrees C for four days before they were
      reanalysed. HPLC quantification of adrenaline was also performed on samples from
      solutions given to 28 different patients. RESULTS: The concentration of
      adrenaline and fentanyl decreased approximately 3.5% from 1 to 180 days at 4
      degrees C and four days at 22 degrees C. The corresponding figure for bupivacaine
      was an apparent increase by 2.4% in concentration. No absorption to the
      polypropylene plastic bags of fentanyl and bupivacaine was detected. None of the
      28 samples derived from used infusion bags contained less than 95% of the
      declared content of adrenaline. CONCLUSIONS: The triple-component epidural
      analgesic solution remained stable during six months of cold storage, followed by
      four days of storage at room temperature. No significant degradation of
      adrenaline was observed in infusion solutions returned from the wards.

PMID- 10939701
TI  - Intrathecal adenosine administration in abdominal hysterectomy lacks analgesic
      effect.
AB  - BACKGROUND: Adenosine (Ado) is known, from studies in both animals and humans, to
      produce antinociception when administered systemically or intrathecally (IT). The
      current aim was to evaluate, in a placebo-controlled, randomised, double-blind
      study, whether IT adenosine given before surgery could reduce anaesthetic
      requirement and the need of opioids during 48 h after visceral surgery. METHOD:
      Forty women (37-66 years, ASA I and II) scheduled for elective hysterectomy were
      included. Before inducing the standardised O2/N2O/isoflurane/fentanyl
      anaesthesia, the patients received an IT injection of either adenosine (500
      microg in 1 ml volume) or placebo 1 ml (saline). Intraoperative anaesthetic drug
      doses and haemodynamics were recorded. Postoperative pain was assessed by visual
      analogue scale. For postoperative analgesia, cetobemidone was provided via
      intravenous patient-controlled analgesia (PCA). RESULTS: During surgery, there
      were no differences between groups in anaesthetic requirement or haemodynamic
      parameters. Postoperative cetobemidone requirements were similar in both groups
      (median 48 mg for adenosine/50 mg for saline) during the first 48 postoperative
      hours. CONCLUSION: IT adenosine did not influence the requirement of anaesthetic
      drug or postoperative analgesics after hysterectomy.

PMID- 10939702
TI  - The effect of dextromethorphan, alone or in combination with ibuprofen, on
      postoperative pain after minor gynaecological surgery.
AB  - BACKGROUND: Experimental studies have demonstrated that peripheral tissue injury
      may lead to hyperexcitability of nociceptive neurones in the dorsal horn, in part
      mediated by N-methyl-D-aspartate (NMDA)-receptor mechanisms. Sensitisation of
      dorsal horn neurones may be an important contributor to postoperative pain. The
      aim of the present study was to investigate the effect of the NMDA-receptor
      antagonist dextromethorphan on pain after minor gynaecological surgery, and to
      evaluate a potential additive effect with ibuprofen. METHODS: In a double-blind,
      placebo-controlled study, 100 patients scheduled for elective termination of
      pregnancy were randomised to receive placebo, oral ibuprofen 400 mg, oral
      dextromethorphan 120 mg, or a combination of ibuprofen 400 mg and
      dextromethorphan 120 mg, 1 h before surgery. Pain and analgesic requirements were
      assessed 0.5, 1 and 2 h after operation. RESULTS: We observed no effect of
      dextromethorphan on visual analogue scale (VAS) pain scores or analgesic
      consumption, and no additive or synergistic analgesic effects between ibuprofen
      and dextromethorphan. Ibuprofen reduced pain scores compared with placebo, and
      analgesic consumption compared with both placebo and dextromethorphan. The
      combination of ibuprofen and dextromethorphan increased preoperative nausea
      compared with both placebo and ibuprofen, whereas no statistically significant
      side effects were observed with dextromethorphan alone. CONCLUSION: No analgesic
      effects of oral dextromethorphan 120 mg on pain after surgical termination of
      labour, and no additive analgesic effects when combined with ibuprofen 400 mg,
      were observed. Ibuprofen reduced both VAS pain scores and analgesic consumption
      compared with placebo.

PMID- 10939704
TI  - Bilateral re-expansion pulmonary edema in a child: a reminder.
AB  - Re-expansion pulmonary edema (RPE) is an uncommon complication of sudden
      reinflation of a lung collapsed by pneumothorax or pleural effusion. We present a
      case of bilateral pulmonary edema following unilateral drainage of a pleural
      effusion in a young child with non-Hodgkin's lymphoma.

PMID- 10939703
TI  - Subcutaneous infiltration with ammonium sulphate 10% does not prolong the local
      anaesthetic duration of lidocaine in humans.
AB  - BACKGROUND: The aim of the present study was to investigate whether a solution of
      ammonium sulphate and lidocaine had a prolonged duration of action compared with
      lidocaine alone after subcutaneous infiltration in human volunteers. METHODS: In
      a double-blind, randomised, controlled trial 12 male volunteers had either 4 ml
      lidocaine 1% (40 mg) or a solution of 4 ml ammonium sulphate 10% and lidocaine 1%
      (40 mg) subcutaneously infiltrated in corresponding skin areas on the right and
      left calf. The duration of the local anaesthetic action of the test medications
      was assessed 1-6 h after the infiltrations using thresholds to mechanical (von
      Frey hairs) and thermal stimulation (heat detection thresholds: HDT, and heat
      pain detection thresholds: HPDT), and by calculation of areas under the curve
      (AUC) for electronic visual analogue scale (VAS) pain ratings (sampled at 2 Hz)
      during a heat stimulation on the test areas for 30 s with a 45 degrees C warm
      thermode. RESULTS: At no assessment were thresholds to mechanical or thermal
      stimulation increased in favour of ammonium sulphate treated legs compared with
      control legs. On the contrary, HPDT were significantly lower in ammonium sulphate
      treated legs than control legs at the 3 h and 4 h assessment after infiltration
      (P<0.02). Similarly, the AUC for the VAS ratings was significantly higher in
      treatment legs compared with control legs 2 h and 3 h after infiltration
      (P<0.05). CONCLUSION: No improvement in local anaesthetic duration of ammonium
      sulphate 10% plus lidocaine 1% compared with lidocaine 1% alone was demonstrated
      early after subcutaneous infiltration in human volunteers.

PMID- 10939706
TI  - Cardiac arrest during spinal anaesthesia: sudden or expected?

PMID- 10939705
TI  - Low-dose prostacyclin in treatment of severe brain trauma evaluated with
      microdialysis and jugular bulb oxygen measurements.
AB  - BACKGROUND: The endogenous substance prostacyclin is a substance with the
      potential to improve microcirculation and oxygenation around contusions in the
      brain following a head trauma by its vasodilatory, antiaggregatory and
      antiadhesive effects. Microdialysis measurements of local concentrations of
      selected interstitial substances in the brain, and measurements of venous jugular
      bulb oxygenation reflecting overall brain oxygenation, might be useful to
      evaluate possible therapeutic effects of a specific therapy, such as treatment
      with prostacyclin. METHODS: This case report study on six patients, of whom five
      were given prostacyclin, includes cerebral microdialysis measurements of
      interstitial lactate (n=5), pyruvate (n=3), glycerol (n=5) and glucose (n=4), and
      is combined with measurements of venous jugular bulb oxygenation in three of the
      patients. One microdialysis catheter was placed adjacent to a contusion, and in
      four of the patients another catheter was also placed in the contralateral less
      injured side for comparison. Low-dose prostacyclin infusion (0.5-1.0 ng kg(-1)
      min(-1)) was started when lactate concentrations in the more injured side was
      raised at a constant level for more than 10 h. The study also includes one
      patient used as control to whom no prostacyclin was given. RESULTS: Lactate was
      markedly lower in the less injured than in the more injured area of the brain.
      During the prostacyclin infusion elevated lactate and lactate/pyruvate ratio were
      reduced. Elevated glycerol decreased, a low glucose increased and jugular bulb
      blood oxygenation increased following start of prostacyclin. The control patient
      showed an increase in lactate and lactate/pyruvate ratio. CONCLUSION: The
      microdialysis data combined with the jugular bulb oxygenation data indicated that
      low-dose prostacyclin exerts effects compatible with improved oxygenation and
      reduced cell damage in the severely traumatised brain.

PMID- 10939707
TI  - Cardiac arrest during spinal anaesthesia.

PMID- 10939708
TI  - Cardiac arrest during spinal anaesthesia.

PMID- 10939709
TI  - High risk of aspiration and difficult intubation in post-esophagectomy patients.

PMID- 10939711
TI  - The effect of age on the B-cell repertoire.
AB  - The antibody repertoire changes with age. This change reflects, in part, the age
      associated impairment in the production of a diverse population of naive B cells
      in the bone marrow and, in part, by the decreased diversification of B cells in
      the germinal center where affinity maturation and isotype switching takes place.
      B cell number is strictly regulated and despite the decreased output of B cells
      by the bone marrow does not decline during aging. Self-renewal of peripheral B
      cells is sufficient to assure the stability of peripheral B cell number. However,
      when B cell production is stressed as, for example, following drug-induced
      lymphopenia, the rate of recovery of B cell number as well as of B cell diversity
      is compromised in old compared to young mice. Finally, aging is associated with
      the appearance of B cell clonal expansions which not only limit the diversity of
      the B cell repertoire but very likely give rise to monoclonal serum
      immunoglobulins and B cell neoplasms.

PMID- 10939710
TI  - Molecular steps of cell suicide: an insight into immune senescence.
AB  - The cellular and molecular basis of immune senescence is unclear. A number of
      mechanisms have been proposed. In this issue of the Journal of Clinical
      Immunology, some of the mechanisms for various immunologic abnormalities in aging
      are presented. In this article, various molecular steps of both death receptor
      and mitochondrial pathways of apoptosis in general are reviewed. In particular,
      the role of apoptosis in T-cell immune senescence is discussed.

PMID- 10939712
TI  - Thymic involution in aging.
AB  - The size of the naive T-cell pool is governed by output from the thymus and not
      by replication. This pool contributes cells to the activated/memory T-cell pool
      whose size can be increased through cell multiplication; both pools together
      constitute the peripheral T-cell pool. Aging is associated with involution of the
      thymus leading to a reduction in its contribution to the naive T-cell pool;
      however, despite this diminished thymic output, there is no significant decline
      in the total number of T cells in the peripheral T-cell pool. There are, however,
      considerable shifts in the ratios of both pools of cells, with an increase in the
      number of activated/memory T cells and the accumulation in older individuals of
      cells that fail to respond to stimuli as efficiently as T cells from younger
      individuals. Aging is also associated with a greater susceptibility to some
      infections and some cancers. An understanding of the causal mechanism of thymic
      involution could lead to the design of a rational therapy to reverse the loss of
      thymic tissue, renew thymic function, increase thymic output, and potentially
      improve immune function in aged individuals.

PMID- 10939714
TI  - Prevention of systemic lupus erythematosus-like disease in (NZBxNZW)F1 mice by
      treating with CDR1- and CDR3-based peptides of a pathogenic autoantibody.
AB  - Two peptides based on the complementarity-determining regions (CDR) of a
      pathogenic murine anti-DNA antibody were employed in an attempt to prevent the
      spontaneous systemic lupus erythematosus (SLE)-like disease of (NZBxNZW)F1 mice.
      Female mice, at the age of 2 months, were injected with either the CDR1- or the
      CDR3-based peptides (pCDR1, pCDR3) subcutaneously or intravenously in aqueous
      solution for a total of 8-10 treatments. A reduction was observed in the total
      and pathogenic IgG2a and IgG3 anti-DNA antibody titers in the CDR-treated groups.
      Treatment reduced the number of mice that developed proteinuria and immune
      complex deposits in their kidneys. The severity of renal pathology was
      significantly reduced in the pCDR3 (P<0.02) and pCDR1 (P< or = 0.05) treated
      mice. Thus, both CDR-based peptides administered in aqueous solution were capable
      of preventing the SLE-like disease in (NZBxNZW)F1 mice, although the beneficial
      effects of pCDR3 appeared to be more pronounced than those of pCDR1 in the
      treated mice.

PMID- 10939713
TI  - The role of telomerase expression and telomere length maintenance in human and
      mouse.
AB  - The molecular regulation of telomere length has been well elucidated by a series
      of elegant studies over the past decade. More recently, experimental evidence has
      accrued that addresses the challenging question of if and how telomere length
      regulation may contribute to normal human aging or to human disease. Recent
      studies in mice have provided a mammalian precedent indicating that telomerase
      deficiency can lead to in vivo dysfunction, most probably as a consequence of
      progressive telomere shortening. In humans, the evidence that telomere shortening
      might lead to in vivo dysfunction is far less direct, although the recent
      description of telomerase deficiency and telomere shortening associated with the
      DKC syndrome is suggestive of such a link. Methodologies exist and continue to be
      developed that are increasingly capable of manipulating telomerase activity and
      telomere length in human cells. It remains to be determined whether
      scientifically rigorous and (equally important) medically ethical approaches will
      emerge to directly assess the ability of telomere length modulation to correct
      functional disorders of human cellular function ex vivo or more challenging
      still, in vivo.

PMID- 10939715
TI  - Immunoglobulin isotypes of anti-myeloperoxidase and anti-lactoferrin antibodies
      in patients with collagen diseases.
AB  - To investigate the prevalence and clinical relevance of immunoglobulin (Ig)
      isotypes of antimyeloperoxidase (MPO) and antilactoferrin (LF) antibodies in
      collagen diseases, enzyme-linked immunosorbent assay was employed to detect the
      Ig isotypes of both antibodies. The purified proteins of MPO and LF were used as
      two major representative antigens for anti-neutrophil cytoplasmic antibodies
      (ANCA) with a perinuclear staining pattern by an indirect immunofluorescent
      technique. We examined 131 serum samples from 79 patients with rheumatoid
      arthritis (RA), 32 with systemic lupus erythematosus (SLE), 14 with progressive
      systemic sclerosis (PSS), 6 with polymyositis/dermatomyositis (PM/DM), and 5 with
      idiopathic crescentic glomerulonephritis who served as positive controls and 36
      healthy subjects who served as controls. A limited number of patients with RA (4
      10%), SLE (6-9%), and PSS (7-14%) but not PM/DM showed positive IgG or IgA anti
      MPO antibody (MPO-ANCA) but not IgM MPO-ANCA. However, 10-20% of RA, 40-60% of
      SLE, 20-36% of PSS but none of the PM/DM patients showed positive IgG, IgA, or
      IgM anti-LF antibody (LF-ANCA). MPO- and LF-ANCA positivity in RA patients was
      correlated with markers of disease activity such as the erythrocyte sedimentation
      rate, C-reactive protein, and serum Ig levels. IgG LF-ANCA but not MPO-ANCA
      positivity in SLE patients also was correlated with the disease activity index
      but not with clinical features. Neither MPO- nor LF-ANCA positivity in PSS
      patients was correlated with any clinical features. Overall, both MPO- and LF
      ANCA were found mainly in RA, SLE, and PSS patients but not in PM/DM patients.
      The Ig isotypes of MPO- and LF-ANCA frequently belonged to both IgG and IgA and
      rarely to the IgM class. Both MPO- and LF-ANCA positivity reflected disease
      activity in RA and SLE rather than specific organ involvement.

PMID- 10939716
TI  - Humoral immunity against glutamic acid decarboxylase and tyrosine phosphatase IA
      2 in Lambert-Eaton myasthenic syndrome.
AB  - Some beta-cell-specific autoantigens also are present in the central nervous
      system. Furthermore, stiff man syndrome, an autoimmune neurological disease, is
      frequently associated with diabetes and shares with this one an anti-GAD and IA-2
      humoral immunoreactivity. We wondered whether these autoantibodies could be found
      in other neurological diseases with a present or supposed autoimmune origin. So,
      anti-GAD65 (GAD65A) and anti-IA-2 (IA-2A) autoantibodies were assayed in various
      neurological diseases. There was a higher prevalence of such antibodies in
      Lambert-Eaton myasthenic syndrome (LEMS) (GAD65A, 35%; IA-2A, 21%; double
      positivity, 18%) compared to amyotrophic lateral sclerosis (18%, 12%, and 12%,
      respectively) and multiple sclerosis (10%, 3%, and 3%, respectively). In LEMS,
      the humoral reaction was more frequent and/or appeared earlier in the
      paraneoplastic forms. The detection of such autoantibodies in patients with small
      cell lung carcinoma (SCLC) without LEMS suggests that these autoantigens, GAD65
      and IA-2, could be produced by SCLC tissue.

PMID- 10939718
TI  - Mycobacterium tuberculosis-secreted protein antigens: immunogenicity in baboons.
AB  - The effective control of tuberculosis (TB) requires the development of improved
      vaccines. It is now well established that Mycobacterium tuberculosis-secreted
      antigens represent promising candidates to be included in subunit vaccine
      preparations. It also is accepted that studies in nonhuman primate models will be
      required to further develop these vaccine preparations. As a necessary step in
      this direction, we have assessed the immunogenicity of M. tuberculosis-secreted
      antigens in baboons. Animals received a total of three intramuscular injections
      consisting of M. tuberculosis culture filtrate proteins resuspended in an
      adjuvant formulation (MPL-SE) and were tested for development of specific
      antibody and cellular responses. All animals produced antibody and cellular
      proliferative responses in the absence of detectable delayed-type
      hypersensitivity reactions. Production of gamma-interferon following stimulation
      of peripheral blood lymphocytes with culture filtrate proteins was either absent
      or present at low levels. Results from this study show that, although M.
      tuberculosis-secreted protein antigens are relatively safe and immunogenic in
      baboons, alternative immunization approaches must be identified for the induction
      of T-helper type 1 responses.

PMID- 10939717
TI  - The mechanism of mononuclear cell infiltration in oral lichen planus: the role of
      cytokines released from keratinocytes.
AB  - To clarify the pathogenesis of oral lichen planus (OLP), we investigated the
      roles of keratinocytes (KC) in mononuclear cell infiltration. When peripheral
      blood mononuclear cells (PBMC) obtained from healthy donors were cultured in the
      presence of culture supernatants of KC separated from the noninflamed gingivae
      (Nor-KC) and cheek mucosae of patients with OLP (OLP-KC), the number of migrated
      PBMC across monolayered human umbilical vein endothelial cells (HUVEC) were
      increased to about 1.3-fold and 1.5-fold of the control level, respectively, with
      increases of the expression of CD11a, CD11b, CD18, and CD49d on PBMC and
      intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and
      endothelial-leukocyte adhesion molecule-1 on HUVEC. The number of migrated PBMC
      was reduced to about 60% of the control level by pretreatment of PBMC with anti
      CD11a or anti-CD18 MAb and reduced to about 70% by pretreatment of HUVEC with
      anti-CD54 MAb. The pretreatment of PBMC with genistein, H-7, wortmannin, or
      exoenzyme C3 decreased the migrated PBMC by about 70 to 90%. In agreement with
      these results, the culture supernatants of OLP-KC up-regulated tyrosine
      phosphorylation of 62-kDa, 70-kDa, and 102-kDa proteins, phosphatidylinositol-3
      kinase, and protein kinase C activities and activated Rho protein level more so
      than did those of Nor-KC. Additionally, actin reorganization with the formation
      of membrane ruffles and lamellipodia was distinctly induced by the culture
      supernatants of OLP-KC. These results indicate that cytokines generated by KC
      transduce their signals in PBMC, up-regulating the expression of cell surface
      adhesion molecules and migration activity with reorganization of actin filaments.

PMID- 10939719
TI  - A unique monoclonal antibody mNI-11 rapidly enhances spread formation in human
      umbilical vein endothelial cells.
AB  - We previously reported a novel monoclonal antibody (MAb), designated mNI-11,
      recognizing an adhesion-associated antigen distinct from any previously reported
      ones. In this article, this adhesion-associated antigen with a molecular weight
      of about 97 kDa was found to be strongly expressed on human umbilical vein
      endothelial cells (HUVECs) by fluorescence-activated cell sorter (FACS) analysis.
      Expression of this antigen on HUVECs was slightly increased in response to the
      exposure to tumor necrosis factor-alpha (TNF-alpha) or phorbol myristate acetate
      (PMA). As a biological function exerted by this antigen, it was of great interest
      that immobilized mNI-11 directly and rapidly enhanced the spread formation of
      HUVECs, whereas MAbs binding other adhesion-associated antigens such as mNI-58A
      (anti-CD11a), L130 (anti-CD18), L133.1 (anti-CD31), L178 (anti-CD44), L25.3 (anti
      CD49d), or LB-2 (anti-CD54) did not carry such activity under the same
      conditions. The HUVECs spread formation enhanced by mNI-11 was completely blocked
      in the presence of a microfilament formation inhibitor, cytochalasin D (CyD), a
      Ca2+ calmodulin inhibitor, W-7, EDTA, and was partially blocked by a microtubule
      formation inhibitor, nocodazole, a protein kinase C (PKC) inhibitor, H-7, and a
      protein synthesis inhibitor, cycloheximide (CHX). However, a protein tyrosine
      kinase (PTK) inhibitor, genistein, did not affect the spread formation under the
      same conditions. Taken together, it was suggested that the spread formation of
      HUVECs enhanced by mNI-11 was mainly associated with the influx of Ca2+ and
      microfilament reorganization. In addition, the novel property associated with mNI
      11 to enhance the spread formation of HUVECs was possibly mediated through its
      reaction against a unique epitope on HUVECs.

PMID- 10939722
TI  - Laser in situ keratomileusis after penetrating keratoplasty.
AB  - PURPOSE: To determine the safety, efficacy, predictability, and stability of
      laser in situ keratomileusis (LASIK) to correct myopia and myopic astigmatism in
      eyes with prior penetrating keratoplasty. METHODS: Eight eyes of 8 patients with
      penetrating keratoplasty had significant postoperative refractive error. Each eye
      received LASIK 1 year or more after penetrating keratoplasty. All were followed
      for 6 months or more. All patients were treated with the Chiron Technolas 217
      excimer laser and the Automated Corneal Shaper microkeratome. RESULTS: Mean
      spherical equivalent refraction decreased from -4.50 D (range, -3.00 to -7.25 D)
      to -0.75 D (range, -1.50 to +0.50 D) and the mean preoperative astigmatism
      decreased from 3.50 D (range, 1.50 to 5.00 D) to 1.25 D (range, 0.75 to 2.00 D).
      Uncorrected visual acuity improved by at least two Snellen lines in all eyes.
      Best spectacle-corrected visual acuity did not change in four eyes (50%) and
      improved in three eyes (37.5%). CONCLUSION: LASIK effectively reduced low and
      moderate myopia and myopic astigmatism following penetrating keratoplasty.

PMID- 10939721
TI  - Arc-scanning very high-frequency digital ultrasound for 3D pachymetric mapping of
      the corneal epithelium and stroma in laser in situ keratomileusis.
AB  - PURPOSE: To test and demonstrate measurement precision, imaging resolution, 3D
      thickness mapping, and clinical utility of a new prototype 3D very high-frequency
      (VHF) (50 MHz) digital ultrasound scanning system for corneal epithelium, flap,
      and residual stromal thickness after laser in situ keratomileusis (LASIK).
      METHODS: VHF ultrasonic 3D data was acquired by arc-motion, meridional scanning
      within a 10-mm zone. Digital signal processing techniques provided high
      resolution B-scan imaging, and I-scan traces for high-precision pachymetry in 4
      eyes. Thickness maps of individual corneal layers were constructed.
      Reproducibility of epithelial, flap, and full corneal pachymetry was assessed for
      single-point and 3D thickness mapping by repeated measures. Thickness mapping of
      the epithelium, stroma, flap, and full cornea were determined before and after
      LASIK. Preoperative to postoperative difference maps for epithelium, flap, and
      stroma were produced to demonstrate anatomical changes in the thickness profile
      of each layer. RESULTS: Surface localization precision was 0.87 microm. Central
      reproducibility for single-point pachymetry of epithelium was 0.61 microm; flap,
      1.14 microm; and full cornea, 0.74 microm. Reproducibility for central pachymetry
      on 3D thickness mapping was 0.5 microm for epithelium and 1.5-microm for full
      cornea. B-scans and 3D thickness maps after LASIK demonstrated resolution of
      epithelial, stromal component of the flap, and residual stromal layers. Large
      epithelial profile changes were demonstrated after LASIK. Topographic variability
      of flap thickness and residual stromal thickness were significant. CONCLUSIONS:
      VHF digital ultrasound arc-B scanning provides high-resolution imaging and high
      precision three-dimensional thickness mapping of corneal layers, enabling
      accurate anatomical evaluation of the changes induced in the cornea by LASIK.

PMID- 10939723
TI  - Results of photorefractive keratectomy in keratoconus suspects at 4 years.
AB  - PURPOSE: We studied the long-term results of photorefractive keratectomy (PRK) in
      keratoconus suspects detected by videokeratography (TMS). METHODS: Bilateral
      inferior corneal steepening was detected in 6 candidates for PRK presenting with
      moderate myopia or astigmatism. Mean follow-up was 44.5 +/- 4.4 months (range, 38
      to 54 mo). Mean spherical equivalent refraction was -5.18 +/- 1.60 D (mean
      sphere, -4.73 D; mean cyclinder, -0.92 D) which was stable for at least the
      preceding year. The quantitative measurement of inferior corneal steepening (I-S
      value) was greater than +1.60 (mean, 1.83 +/- 0.11) in all eyes. An Aesculap
      Meditec Mel 60 excimer laser was used for the PRK procedures and mean follow-up
      was 44.5 months. Postoperative pachymetric measurements were also performed in 6
      eyes. RESULTS: Postoperative uncorrected visual acuity was 20/20 in 8 eyes
      (66.6%) and 20/32 or better in all eyes with a mean postoperative spherical
      equivalent refraction of -0.70 +/- 0.74 D (mean sphere, -0.63 D; mean cyclinder, 
      0.39 D). Five eyes (41.6%) were within +/- 0.50 D spherical equivalent
      refraction. Inferior steepening was associated with thinning of the inferior
      cornea which was statistically significantly thinner than the superior thickness
      (Student's t-test, P < .05). There were no wound healing problems or any sign
      that the excimer laser adversely affected the cornea during follow-up.
      CONCLUSIONS: Photorefractive keratectomy seems to be a safe procedure for
      reducing or eliminating myopia or astigmatism in keratoconus suspect eyes-most
      probably forme fruste keratoconus-with a stable refraction, but this may be
      different in eyes with early keratoconus, known to be a progressive disease.

PMID- 10939720
TI  - The cornea is not a piece of plastic.

PMID- 10939724
TI  - Topical tetracaine with bandage soft contact lens pain control after
      photorefractive keratectomy.
AB  - PURPOSE: A major disadvantage of photorefractive keratectomy (PRK) is pain and
      discomfort in the first three postoperative days. We tried to assess the efficacy
      and safety to the cornea of a limited amount of topical tetracaine given to
      patients for use when needed to manage severe pain. METHODS: Sixty-nine eyes of
      49 patients who underwent PRK between June 21, 1996 and June 15, 1998 by a single
      surgeon were prospectively included. Approximately 10 drops of commercial, non
      preserved 0.5% tetracaine were given to patients to use when needed to control
      severe pain. A bandage soft contact lens was applied. Patients were examined at 1
      and 3 days after surgery, at which time corneal re-epithelization was assessed
      and the number of tetracaine drops used was noted. No systemic analgesic or
      topical non-steroidal anti-inflammatory was prescribed. RESULTS: All eyes healed
      within 3 days. The mean number of drops of tetracaine used was 2.3 drops over 3
      days, although in 33 eyes (48%) the patient did not use any tetracaine. There was
      no correlation between the attempted correction in diopters and the number of
      drops used. No significant difference was found in the number of drops used in
      the second eye of patients who had both eyes treated. CONCLUSIONS: Limited use of
      topical anesthetics is an effective and safe analgesic option after PRK. Use of
      tetracaine in this protocol did not prolong the time to re-epithelialization.
      Giving only a limited amount of tetracaine to patients prevents abuse and
      toxicity to the cornea while managing severe pain.

PMID- 10939725
TI  - Hyaluronidase treatment, collagen fibril packing, and normal transparency in
      rabbit corneas.
AB  - PURPOSE: Hyaluronidase treatment is the initial step of corneaplasty, a treatment
      under development that induces stromal softening and involves the application of
      a custom designed forming lens to achieve modification of refractive error. The
      purpose of this investigation was to examine changes in the arrangement of
      stromal collagen fibrils after hyaluronidase treatment. METHODS: Rabbit corneas
      were evaluated by slit-lamp microscopy at 0, 2 and 7 days after treatment and
      haze was assessed by subjective observation. Molecular and interfibrillar Bragg
      spacing of corneal collagen were measured from synchrotron x-ray scattering
      patterns. Transmission electron microscopy and digital image analysis were used
      to calculate radial distribution functions from the positions of collagen
      fibrils. The calculated fibril sizes and positions were also used to predict the
      transmission of visible light through these corneas. RESULTS: Hyaluronidase
      treated corneas were shown to have a decreased interfibrillar Bragg spacing of
      15% to 21%. Fibril hydration did not change. Transparency of these corneas
      remained unaltered. CONCLUSIONS: Hyaluronidase reduced the hydration of the
      corneal stroma, which led to a more compacted collagen fibril arrangement. This
      compression was predicted to cause a small reduction in the transmission of
      visible light through the cornea but not to a point likely to cause visual
      impairment.

PMID- 10939726
TI  - Implantation of scleral-sutured posterior chamber intraocular lenses during
      penetrating keratoplasty.
AB  - PURPOSE: To evaluate the clinical outcome in 29 patients (29 eyes) who underwent
      penetrating keratoplasty and scleral-fixation of an intraocular lens. METHODS:
      The indications for penetrating keratoplasty with scleral-fixation of an
      intraocular lens were anterior chamber pseudophakic corneal edema, aphakic
      corneal edema, trauma, and corneal scars. Patients with pseudophakic corneal
      edema underwent IOL exchange and penetrating keratoplasty and patients with lens
      subluxation underwent cataract extraction and penetrating keratoplasty in the
      same operation session. RESULTS: Preoperative spectacle-corrected visual acuity
      was hand motion in 13 eyes (44.8%) and 20/400 in 18 eyes (61.5%). Postoperative
      spectacle-corrected visual acuity of 20/400 or better was observed in 25 eyes
      (86.2%). At last follow-up, 26 corneal grafts (89.7%) remained clear. Three
      grafts (10.3%) failed, two because of glaucoma and one because of
      endophthalmitis. Glaucoma was observed in 7 eyes. CONCLUSION: Trans-scleral
      fixation of intraocular lenses combined with penetrating keratoplasty was a
      useful surgical technique in eyes with keratopathy and lacking posterior capsular
      support.

PMID- 10939727
TI  - Standard graphs for reporting refractive surgery.

PMID- 10939729
TI  - Outcomes of retreatment after laser in situ keratomileusis.

PMID- 10939728
TI  - Nocardia keratitis after traumatic detachment of a laser in situ keratomileusis
      flap.
AB  - PURPOSE: Nocardia are gram-positive bacteria existing ubiquitously in the
      environment; they can cause keratitis. Nocardia asteroides keratitis occurred in
      the interface between the stromal bed and flap after traumatic detachment of the
      flap 4 months after an initially uncomplicated laser in situ keratomileusis
      (LASIK) procedure. METHODS: Nocardia asteroides keratitis was confirmed by
      culture. Therapy included topical and oral trimethoprim-sulfamethoxazole.
      RESULTS: Thirteen months after the trauma, the patient's spectacle-corrected
      visual acuity was 20/20 with a manifest refraction of -2.25 -1.00 x 30 degrees.
      CONCLUSIONS: The immediate steps of management consisting of surgically lifting
      the corneal flap, rapid microbial identification, and proper treatment with
      specific antibiotics resulted in the successful treatment of Nocardia asteroides
      keratitis in a traumatized eye after LASIK.

PMID- 10939730
TI  - Classification of corneal topographic patterns after PRK.

PMID- 10939731
TI  - PRK over incomplete LASIK flap.

PMID- 10939732
TI  - Configurational control in stereochemically pure ligands and metal complexes for
      asymmetric catalysis
AB  - Enantioselective synthesis relies on suitable chiral mediators, which, in many
      cases, owe their stereochemical information to chiral ligands coordinated to
      metals. Like nature, which uses (diastereomerically pure) enzymes with several
      stereogenic centers to catalyze biological processes, chemists, for their
      purposes, tend more and more to turn their attention towards ligands and metal
      complexes with more than one stereogenic center or element of chirality. Selected
      issues of the resulting diastereomeric interactions as well as the advantages
      that result from the use of such complexes in catalysis are presented and
      discussed here.

PMID- 10939733
TI  - Topographical analyses of homonuclear multiple bonds between main group elements
AB  - Recent experiments have resulted in the completion of the series of Group 14 and
      Group 15 element double-bond systems, R(n)E=ER(n) (E = C - Pb, n = 2; E = N - Bi,
      n = 1). Furthermore, new families of multiple-bonded species have been
      discovered, such as the radical anion [RSnSnR](-) , the close ion pairs
      [RE(mu2Na)2ER] (E = Ge,Sn), and a digallyne [RGa(mu2Na)2GaR] for which a Ga=Ga
      triple bond was formulated. Some of these compounds show classical multiple bond
      features (i.e. the dipnictogens RE=ER, E=N-Bi) in the sense that planar
      structures with short E-E distances are observed. However, many (i.e. R2E=ER2, E
      = Si - Pb) do not behave as expected for compounds with multiple bonds. They have
      trans bent structures, show enormous variation in their E-E distances, and some
      dissociate easily under E-E bond cleavage in solution. These properties raised
      doubts as to whether these compounds can be formulated as multiple-bonded
      systems. Using the electron localization function (ELF) it is possible to clearly
      show the topographical similarities between classical and nonclassical multiple
      bonds; ELF divides these systems into unslipped (classical) and slipped
      (nonclassical) systems. ELF can also be employed to confirm the nonexistence of
      multiple bonds. Therefore, topographical analyses using ELF are useful to
      categorize a bonding system. In particular, the bonds in the heavier Group 14
      double systems and the Ga-Ga bond in digallyne are clearly shown by this method
      as slipped double and triple bonds, respectively.

PMID- 10939734
TI  - Structure and lipophilicity profile of 2,3-anhydro-alpha-cyclomannin and its
      ethanol inclusion complex.
AB  - Readily available from alpha-cyclodextrin in three steps, 2,3-anhydro-alpha
      cyclomannin composed of six alpha-(1-->4)-linked 2,3-anhydro-D-mannopyranose
      residues, crystallizes well when precipitated from aqueous ethanol. An X-ray
      structure reveals the macrocycle to contain ethanol in its cavity, thus
      representing the first inclusion complex of a non-glucose cyclooligosaccharide.
      The wider rim of the torus-shaped macrocycle holds the six epoxide rings whose
      oxygens point away from the cavity, thereby sculpturing the unique over-all shape
      of a six-pointed star.

PMID- 10939735
TI  - The C-F...cation interaction: an ammonium complex of a hexafluoro macrocyclic
      cage compound.
AB  - An ammonium complex of the hexafluoro cage compound 1 was isolated and its
      structure was elucidated by X-ray crystallographic analysis. The C-F bonds are
      elongated by the complexation, which is clear evidence of C-F...cation
      interaction. The driving force of NH4(+) inclusion is the C-F cation interaction,
      but the C-F...HN+ hydrogen bond does not contribute to this complexation. The
      crystal structure of the NH4+ complex 1 shows short C-F...HN+ contacts (2.286
      2.662 A). Furthermore, it shows that closer F...H(+)(-N) distances give a larger
      F...H(+)-N angle. Although such structural features seem to indicate the
      existence of C-F...HN+ hydrogen bonds, the spectral data (1H NMR, 19F VT-NMR, and
      IR spectroscopy) did not support the existence of hydrogen bonds. Thermodynamic
      parameters, log K(s) (4.6 +/- 0.1, 298 K), deltaH (-5.3 +/- 0.1 kcal mol(-1)),
      and deltaS (3.2 +/- 0.3 cal mol(-1) K(-1)), of the complexation were obtained in
      CDCl3/CD3CN mixture.

PMID- 10939736
TI  - Understanding the structural properties of a homologous series of bis
      diphenylphosphine oxides
AB  - A homologous series of bis-diphenylphosphine oxides (C6H5)2PO(CH2)(n)PO(C6H5)2
      (with n = 2-8; denoted 2-8] have been investigated to explore the effects of a
      range of competing and cooperative intermolecular and intramolecular interactions
      on the structural properties in the solid state. The important factors
      influencing the structural properties include intramolecular aspects such as the
      conformation of the aliphatic chain and the intramolecular interaction between
      the two P=O dipoles in the molecule, and intermolecular aspects such as long
      range electrostatic interactions (dominated by the arrangement of the P=O
      dipoles), C-H...O interactions, C-H...pi interactions and pi...pi interactions.
      Compounds 3 and 5 could be crystallized only as solvate co-crystals (3 water and
      5 x (toluene)2], whereas the crystal structures of all the other compounds
      contain only the bis-diphenylphosphine oxide molecule. The crystal structures
      have been determined from single-crystal X-ray diffraction data, with the
      exception of 7 (which has been determined here from powder X-ray diffraction
      data) and 4 (which was known previously). The compounds with even n represent a
      systematic structural series, exhibiting characteristic, essentially linear
      P=O...P=O...P=O dipolar arrays, together with C-H...O and C-H...pi interactions.
      For the compounds with odd n, on the other hand, uniform structural behaviour is
      not observed across the series, although certain aspects of these crystal
      structures contribute in a general sense to our understanding of the structural
      properties of bis-diphenylphosphine oxides. Importantly, for the compounds with
      odd n, there is "frustration" with regard to the molecular conformation, as the
      preferred all-anti conformation of the aliphatic chain gives rise to an
      unfavourable parallel alignment of the two P=O dipoles within the molecule.
      Clearly the importance of avoiding a parallel alignment of the P=O dipoles
      becomes greater as n decreases. Local structural aspects (investigated by high
      resolution solid-state 31P NMR spectroscopy) and thermal properties of the bis
      diphenylphosphine oxide materials are also reported.

PMID- 10939737
TI  - Stereochemistry of phenyl alpha-nitronyl nitroxide radicals
AB  - An extensive investigation of the conformations adopted by the family of phenyl
      alpha-nitronyl nitroxides has been carried out. A database containing 110 crystal
      structures was used in a statistical study of the solid-state geometries and
      conformations of these radicals. This study revealed that the favoured
      conformations involve a twisted distortion in the imidazolyl rings and a twist
      between the aromatic and heterocyclic rings in the molecules. As a consequence,
      these radicals show two types of preferred conformations in the solid state: the
      pseudo-anti enantiomeric pair and the pseudo-eclipsed pair, the latter type being
      the most statistically probable. A new chiral member of this group of radicals
      that bears a lactate moiety, (R)-1, and its corresponding racemic compound, (R,S)
      1, have been prepared in order to study the influence of chiral induction from
      the stereogenic centre on the torsion angle between the aromatic and heterocyclic
      rings of the alpha-nitronyl nitroxides. The X-ray crystal structures of the
      enantiopure and racemic compounds, which both reveal chains of molecules
      sustained by strong O-H...O hydrogen bonds between the carboxylic acid group and
      the ON group of the radical in the solid, as well as their magnetic properties
      have been determined. Remarkably, the molecules with a given stereogenic centre
      have a single helical sense between their component rings, even in the racemic
      crystal. Chiral induction from the stereogenic centre to the radical unit has
      also been proved by CD spectroscopy in the solid state. The results of these
      experiments have been rationalised by ab initio calculations of the spectra.

PMID- 10939738
TI  - Synthesis and an X-ray structure of soluble phenylacetylene macrocycles with two
      opposing bipyridine donor sites
AB  - The synthesis of the shape-persistent macrocycles 10a and 10b with two bipyridine
      units in opposing sides by Hagihara/Sonogashira cross-coupling chemistry of
      suitably functionalized building blocks is reported. X-ray analysis of single
      crystals of 10b shows a layered structure with channels filled with solvent
      molecules and parts of the flexible chains. with which the cycle is decorated for
      solubility reasons.

PMID- 10939739
TI  - Formation of carboxylic acids from small alkanes in zeolite H-ZSM-5
AB  - The activation of propane and isobutane in acidic zeolite H-ZSM-5 in the presence
      of both CO and H2O has been studied by in situ solid-state NMR and GC analysis.
      Evidence was provided for the conversion of propane to isobutyric acid at 373-473
      K by cleavage of the C-C bond; methane and ethane are also produced. Isobutane is
      transformed into pivalic acid with simultaneous production of hydrogen. The low
      conversion (1-2%) at this temperature was rationalized by the existence of a
      small number of sites that are capable of generating carbenium ions which are
      trapped by CO at this temperature. A formate species was observed when CO and H2O
      were present on H-ZSM-5. This species disappeared in the presence of the alkane.
      At 573 K, the generation of large amounts of CO2 indicates a much higher
      conversion of the alkanes into carboxylic acids which, however, decompose under
      the reaction conditions.

PMID- 10939740
TI  - C-H-pi interactions in 1-n-butyl-3-methylimidazolium tetraphenylborate molten
      salt: solid and solution structures
AB  - The crystal structure of 1-n-butyl-3-methylimidazolium tetraphenylborate molten
      salt (1) shows C-H-pi interactions between the hydrogens of the imidazolium
      cation and the phenyl rings of the tetraphenylborate anion. The imidazolium ring
      is surrounded by three tetraphenylborate anions that are connected with the same
      cation by C-H-pi (phenyl rings) interactions. The nearest inter-ion interaction
      is found between the N-CH-N proton of the cation and the B-phenyl centroid (2.349
      A) with a nearly T-shaped geometry. The inter-ionic solution structure of 1 has
      been investigated by the detection of inter-ionic contacts in 1H NOESY NMR
      spectra between the protons of the cation and the anion. The 1H-NMR spectra of
      molten salt 1 is almost independent of its concentration in [D6]DMSO solution,
      the imidazolium proton chemical shifts are in the expected region and there are
      no observable NOE effects between the protons of the cation with those of the
      anion, indicating that 1 behaves in [D6]DMSO as a solvent-separated ion pair. In
      CDCl3 the 1H-NMR spectra of 1 are concentration dependent and all the imidazolium
      protons are shielded as compared with those observed in [D6]DMSO. Moreover, the
      1H NOESY NMR spectra show all the peaks affected by the interaction between the
      protons of the imidazolium cation and those of the anion, indicating that in
      CDCl3 1 possesses a contact ion pair structure. The NCHN proton of the cation
      exhibits the greatest shielding (up to -4.5 ppm). an indication of the existence
      of C-H-pi interactions, even in solution. The calculated distance of this proton
      to the phenyl centroid is 2.3 A for a C-H -pi angle of 180 degrees. The apparent
      volumes for the cation and anion, calculated from the measured 13C-NMR relaxation
      times, increase from 38 and 140 A3 in [D6]DMSO to 360 and 600 A3 in CDCl3,
      respectively; this indicates the formation of floating aggregates of the type
      (1)(n) in CDCl3 via weak hydrogen bonds, with increasing concentration.

PMID- 10939741
TI  - A convergent total synthesis of (-)-mucocin: an acetogenin from Annonaceae.
AB  - A total synthesis of the Annonaceous acetogenin mucocin has been accomplished.
      The synthesis follows a convergent strategy, wherein at a very late stage the
      left part of the molecule is connected with the right part. The key reaction is
      the stereocontrolled addition of an organomagnesium compound 2 to the aldehyde 3.
      The THP ring of mucocin is build by a 6-endo epoxide cyclization of an
      epoxyacetonide precursor (16 --> 17). The new modular synthetic approach
      developed herein should be useful for the synthesis of other related natural
      products as well as pharmacologically interesting analogues.

PMID- 10939742
TI  - Reduction of bis
AB  - The reduction of symmetric, fully-substituted titanocene dichlorides bearing two
      pendant omega-alkenyl groups, [TiCl2(eta5-C5Me4R)2], R = CH(Me)CH= CH2 (1a).
      (CH2)2CH=CH2 (1b) and (CH2)3CH=CH2 (1c), by magnesium in tetrahydrofuran affords
      bis(cyclopentadienyl)titanacyclopentanes [Ti(IV)[eta1:eta1: eta5:eta5
      C5Me4CH(Me)CH(Ti)CH2CH(CH2(Ti))CH(Me)C5Me4]] (2a), [Ti(IV)[eta1:eta1:eta5: eta5
      C5Me4(CH2)2CH(Ti)(CH2)2CH(Ti)(CH2)2C5Me4]] (2b) and [Ti(IV)[eta1:eta1:eta5:eta5
      C5Me4(CH2)2CH(Ti)CH(Me)CH(Me)CH(Ti)(CH2)2C5Me4]](2c), respectively, as the
      products of oxidative coupling of the double bonds across a titanocene
      intermediate. For the case of complex 1c, a product of a double bond
      isomerisation is obtained owing to a preferred formation of five-membered
      titanacycles. The reaction of the titanacyclopentanes with PbCl2 recovers
      starting materials 1a from 2a and 1b from 2b, but complex 2c affords, under the
      same conditions, an isomer of 1c with a shifted carbon - carbon double bond,
      [TiCl[eta5-C5Me4(CH2CH2CH=CHMe)]2] (1c'). The titanacycles 2a-c can be opened by
      HCl to give ansa-titanocene dichlorides ansa-[[eta5:eta5
      C5Me4CH(Me)CH2CH2CH(Me)CH(Me)C5Me4]TiCl2] (3a), ansa-[[eta5:eta5
      C5Me4(CH2)8C5Me4]TiCl2] (3b), along with a minor product ansa-[[eta5:eta5
      C5Me4CH2CH=CH(CH2)5C5Me4]TiCl2] (3b'), and ansa-[[eta5:eta5
      CsMe4(CH2)3CH(Me)CH(Me)CH=CHCH2C5Me4]TiCl2] (3c), respectively, with the bridging
      aliphatic chain consisting of five (3a) and eight (3b, 3b' and 3c) carbon atoms.
      The course of the acidolysis changes with the nature of the pendant group; while
      the cyclopentadienyl ring-linking carbon chains in 3a and 3b are fully saturated,
      compounds 3c and 3b' contain one asymetrically placed carbon-carbon double bond,
      which evidently arises from the beta-hydrogen elimination that follows the HCl
      addition.

PMID- 10939743
TI  - pH-independent triple-helix formation with 6-oxocytidine as cytidine analogue.
AB  - The syntheses of six different phosphoramidite building blocks of 6-oxocytosine
      and 5-allyl-6-oxocytosine as analogues of N(3)-protonated cytosine are described.
      These compounds have been incorporated into oligonucleotides by standard solid
      phase synthesis. Hybridization of 15-mer Hoogsteen strands with target 21-mer
      duplexes was investigated. Comparison of the triplex-forming abilities of the
      different building blocks revealed that: i) 5-allyl substitution has a negative
      influence on triplex stability, ii) a uniform backbone of the Hoogsteen strand
      stabilizes triplexes relative to mixed backbones; iii) RNA strands with 6
      oxocytidine or 5-allyl-6-oxocytidine do not form a triple helix with the DNA
      target duplex, probably due to backbone torsional constraints; and (iv) a 15-mer
      DNA sequence with three isolated 2'-deoxy-6-oxocytidines has the highest T(m) of
      all cytidine analogues investigated in this study. CD experiments provided
      further evidence for the presence or absence of triplex structures. In the course
      of these temperature-dependent CD measurements we were able to detect duplex and
      triplex melting independent from each other at selected wavelengths. This
      methodology is especially interesting in cases where UV melting curves show only
      one transition owing to spectral overlap.

PMID- 10939744
TI  - pi bonding in second and third row molecules: testing the strength of Linus's
      blanket
AB  - The flexibility of valence bond (VB) theory provides a new method of calculating
      pi-bond energies in the double-bonded species H(m)A=BH(n), where A, B = C, N, O,
      Si, P, S. This new method circumvents the problems usually associated with
      obtaining pi-bond strengths by targeting only the pi bond, while all other
      factors remain constant. In this manner, a clean separation between sigma- and pi
      effects can be achieved which highlights some expected trends in bond strength
      upon moving from left to right and up and down the Periodic Table. Intra-row pi
      bonds conform to the classic statement by Pauling [L. Pauling, The Natiure of the
      Chemical Bond, Cornell University Press, Ithaca, 1960, 3rd edition] regarding the
      relationship of heteronuclear bond strengths to their homonuclear constituents
      whereas inter-row pi bonds do not. This variance with Pauling's statement is
      shown to be due to the constraining effect of the underlying sigma bonds which
      prevents optimal p(pi)-p(pi) overlap. While Pauling's statement was based on the
      assumption that the resonance energy (RE) would be large for heteronuclear and
      small for homonuclear bonds, we have found large REs for all bonds studied
      herein; this leads to the conclusion that REs are dependent not only on the
      electronegativity difference but also the electronegativity sum of the
      constituent atoms. This situation where the bond is neither covalent nor ionic
      but originates in the covalent-ionic mixing has been termed charge shift (CS)
      bonding [S. Shaik, P. Maitre, G. Sini, P. C. Hiberty, J. Am. Chem. Soc. 1992,
      114, 7861]. We have shown that CS bonding extends beyond single sigma bonds in
      first row molecules, thus supporting the idea that CS-bonding is a ubiquitous
      bonding form.

PMID- 10939745
TI  - Catalytic enantioselective aza-Diels-alder reactions of imines--an approach to
      optically active nonproteinogenic alpha-amino acids
AB  - A catalytic enantioselective aza-Diels-Alder reaction of imines has been
      developed. The reaction of N-tosyl alpha-imino ester with different dienes
      including activated, non-activated, cyclic, and acyclic dienes has been
      investigated in the presence of various chiral Lewis acids. A series of phosphino
      oxazoline ligands have been synthesized and evaluated for the reaction. It was
      found that the combination of phosphino-oxazoline ligands with copper(I) salts
      gives the best results for the activated dienes, while BINAP-copper(I) complexes
      are good catalysts for all the dienes studied. In the case of activated acyclic
      dienes the aza-Diels-Alder products can be obtained in higher than 80% isolated
      yield and 96% ee, while for the unactivated cyclic dienes the exo diastereomer is
      formed as the major product in up to 95 % ee. For an activated cyclic conjugated
      diene, 2-trimethylsilyloxy-1,3-cyclohexadiene, the reaction proceeds as a Mannich
      type addition reaction giving optically active gamma-oxo alpha-amino acid
      derivatives in good yields and up to 96% ee. The reaction of an unactivated
      acyclic diene, 2,3-dimethyl-1,3-butadiene, with the N-tosyl alpha-imino ester
      gives both the aza-Diels-Alder and aza-ene products, in a ratio of 9:1 favoring
      the aza-Diels-Alder product. Furthermore, a series of different imines have been
      synthesized and investigated as possible substrates for the present catalytic
      enantioselective aza-Diels-Alder reaction in order to obtain mechanistic insight.
      All imines studied gave moderate to high ee. Particularly, the reaction of the N
      phenyl and N-p-methoxyphenyl substituted glyoxylate imines with Danishefsky's
      diene proceeded well affording the corresponding aza-Diels-Alder product in high
      yield with up to 91% ee at room temperature. The present catalytic
      enantioselective reaction of imines provided an effective route to optically
      active nonproteinogenic alpha-amino acids. The products of the catalytic
      enantioselective aza-Diels-Alder reaction of the cyclic dienes can be used for
      the preparation of key compounds such as natural products and compounds of
      pharmaceutical interest. The absolute configurations of five products have been
      solved by X-ray structural analysis, and it is found that the absolute
      configuration of the aza-Diels-Alder adduct is dependent on the substituent on
      the imine nitrogen atom. It turned out that the N-tosyl glyoxylate imine and N-p
      methoxyphenyl glyoxylate imine give the aza-Diels-Alder adduct with opposite
      absolute configuration using the same enantiomer of the catalyst. On the basis of
      the results the mechanistic aspects for the reactions are discussed.

PMID- 10939746
TI  - Nitronate anion recognition and modulation of ambident reactivity by hydrogen
      bonding receptors.
AB  - Nitronate anions were shown to form complexes in DMSO with hydrogen-bonding
      receptors such as 1,3-dimethylthiourea 1 (K(a)= 120M(-1)) and bicyclic
      guanidinium 2 (K(a) = 3200M(-1)). A ditopic bis-thiourea exhibited increased
      association with substrates, that contained either two nitronates (K(a)= 7000M(
      1)) or a combination of nitronate and carboxylate (K(a)=7200M(-1)). Complexation
      of nitronate resulted in a change in the ambident reactivity during alkylation
      with p-nitrobenzyl bromide. The predominant reaction pathway was shifted from
      oxygen alkylation to carbon alkylation as receptor binding strength increased.
      Kinetic analysis indicated an overall inhibition of nitronate reactivity, and
      this suggests that greater suppression of the oxygen pathway allows carbon
      alkylation to predominate.

PMID- 10939747
TI  - Electrostatic core shielding in dendritic polyglutamic porphyrins.
AB  - Polyglutamic dendritic porphyrins of the general formula H2PophGlu(N)OR (H2Porph
      = free-base meso-tetra-4-carboxyphenylporphyrin (H2TCPP), Glu=dendrimer layer
      composed of L-glutamates, N= 1-3: dendrimer generation number, R = terminal group
      (All, H)) were synthesized and characterized with NMR and MALDI-TOF mass
      spectroscopy. The free-acid terminated compounds were found to be highly soluble
      in water, with both their absorption and fluorescence spectra dependent on pH.
      The value of the porphyrin mono-protonation constant, measured by fluorescence
      rationing, increased monotonously in the studied series of dendrimers (pK3=6.31.
      6.70, and 6.98, for N=1, 2, 3, respectively). For the largest dendrimer,
      H2PorphGlu(3)OH, pK3 was found shifted by almost two pH units relative to the non
      modified H2Porph. The second protonation constant (K4) was much less affected by
      the dendritic substituents. At pH values less than 3.5 there were noticeable
      changes in fluorescence intensity and quantum yield even for the highly soluble
      H2PorphGlu(3)OH. This suggests that interactions between individual dendritic
      molecules in solution are favored by full protonation of the peripheral glutamic
      carboxyls. The "dendrimer-protected" porphyrins are convenient fluorescent pH
      sensors in the biological pH range.

PMID- 10939748
TI  - Stilbenoid dendrimers
AB  - The first five generations of the stilbenoid dendrimers 1(n) (n = 1-5) have been
      prepared by a combined coupled synthesis (between the generations of the dendrons
      8-12) and convergent synthesis. Wittig-Horner reactions together with a
      protecting group technique yield monodisperse compounds of high constitutional
      and configurational purity. The solubility of the stiff molecules, which have
      primarily a disklike shape in the first and second generations and a cylindrical
      shape in the third, fourth, and fifth generations, is governed by the alkoxy
      chains that are attached to the peripheral benzene rings. The number of stilbene
      building blocks increases according to the formula 3(2(n)-1) from 3 in the first
      generation (n = 1) to 93 in the fifth generation (n = 5). Consequently, the
      molecular mass reaches 24,000 in 1(5)b which contains 144 hexyloxy chains. An
      exact measurement of the mass is provided by matrix-assisted laser desorption
      ionization time-of-flight (MALDI-TOF) mass spectrometry. In solution, the
      stilbenoid dendrimers 1(n) exhibit a strong tendency to aggregate, which
      increases from generation to generation. In the pure state, columnar mesophases
      Col(hd) (1(1)b, 1(1)c, 1(2)b, and 1(2)c) and Col(ob) (1(2)b, 1(2)c) are formed;
      intramolecular steric hindrance prevents such ordered arrangements in higher
      generations 1(n) (n = 3, 4, 5).

PMID- 10939749
TI  - Hemispiroalkaplanes: hydrocarbon cage systems with a pyramidal-tetracoordinate
      carbon atom and remarkable basicity
AB  - A new class of saturated hydrocarbons, in which a spiropentane-type unit is bound
      by a cyclic hydrocarbon, has been investigated by using ab initio molecular
      orbital calculations at the B3-LYP and MP2 levels. These molecules have been
      given the trivial name hemispiroalkaplanes. Hemialkaplanes, which are analogous
      molecules built-up from a neopentane-type unit and a cyclic hydrocarbon, have
      also been examined. The hemispiroalkaplanes are predicted to contain a pyramidal
      tetracoordinate carbon atom that possesses a lone pair of electrons. Protonation
      at this apical carbon atom is found to be highly favourable, resulting in a
      remarkably high basicity for a saturated hydrocarbon. The proton affinities of
      the hemispiroalkaplanes are calculated to be more than 1170 kJmol(-1), even
      greater than that of the diamine "proton sponges". Structural parameters, heats
      of formation and strain energies for the novel hydrocarbons are detailed.

PMID- 10939750
TI  - Progression of renal failure in patients with compromised renal function is not
      always present: evaluation of underlying disease.
AB  - BACKGROUND: It has been proposed that, once renal function has been restricted in
      chronic kidney disease, compensatory hyperfiltration results in a compulsory
      deterioration of renal function. PATIENTS AND METHODS: In this study, 83 patients
      originally starting from a serum creatinine (S(crea)) between 2.0 and 5.0 mg/dl
      were followed for the evolution of renal function. This overall population, with
      a follow-up (FU) of(M +/- SD) 67 +/- 50 months, was stratified into two groups
      based upon their slope of 1/S(crea), whereby the median of this slope (-0.0019)
      was taken as the cut-off value. RESULTS: There was an expected decline of renal
      function in the group with the lowest slope (group A = progression) whereas renal
      function remained stable in the group with the highest slope (group B = no
      progression). This evolution occurred in spite of a similar S(crea) in both
      groups at the start of the study (group A: 2.45 +/- 0.71 mg/100 ml (n = 41) vs.
      group B: 2.94 +/- 0.88 mg/100 ml (n = 42); p = ns) and an even higher creatinine
      clearance in group A (group A: 46.43 +/- 18.65 mg/100 ml(n = 41)vs. group B:
      34.03 +/- 20.11 mg/100 ml (n = 42); p = 0.0049). Group B contained a higher
      number of patients with interstitial nephritis (34/42 = 81% vs. 6/41 = 15%; p <
      0.00001) while patients with chronic glomerulopathy could be found especially in
      group A (23/41 = 56% vs. 8/42 = 19%; p < 0.00001). Proteinuria was continuously
      higher in group A (start FU: p = 0.0097; FU 72 months: p = 0.0155) and tended to
      decrease in group B (start FU, 0.89 +/- 1.42 g/l (n = 42) vs. FU 72 months, 0.41
      +/- 0.78 g/l (n = 26); p = 0.0474) whereas no significant decrease was observed
      in group A (start FU, 2.16 +/- 2.83 g/l (n = 41) vs. FU 72 months, 1.77 +/- 0.72
      g/l (n = 6); p = ns). CONCLUSION: Within the time limit and patient inclusion
      criteria of this FU, a compromised renal function does not necessarily result in
      a further decline. This study points more towards a major role for the underlying
      nature of renal disease.

PMID- 10939751
TI  - Contrast-induced nephrotoxicity in renal allograft recipients.
AB  - BACKGROUND: Intravenous administration of radiographic contrast agents is an
      important cause of acute renal failure, accounting for one third of the cases of
      hospital-acquired acute renal failure in patients with native kidneys. The safety
      of intravenous contrast has not been studied in renal allograft recipients since
      the availability of cyclosporine as a maintenance immunosuppressive therapy. As
      patients with renal transplantation may be at a higher risk of contrast-induced
      nephrotoxicity (CIN) due to concomitant use of cyclosporine and higher prevalence
      of diabetes and renal insufficiency, we retrospectively studied development of
      CIN in these patients. PATIENTS AND METHODS: We identified 44 patients (1988
      1997) with functioning renal allograft who underwent different intravenous or
      intraarterial contrast studies (ICS). Pre- and post-ICS renal function tests were
      done in 35 of these patients. The following were the various ICS done in these
      patients: coronary angiogram (6), CT scan with intravenous contrast ( 11),
      angiogram for evaluation of peripheral vascular disease (11), allograft angiogram
      with angioplasty (5), pulmonary angiogram (1) and intravenous pyelogram (1). The
      mean age of the patients was 42 +/- 2.1 years and the mean serum creatinine was
      2.3 +/- 0.25 mg/dl (mean +/- SEM). Fourty percent of patients (14 of 35) had
      diabetes, and 25.7% (9 of 35) had chronic rejection. Ninety four percent (33 of
      35) of the patients were taking cyclosporine at the time of ICS. RESULTS: Nine
      patients had > or = 25% increase in serum creatinine from baseline after ICS. Two
      of these patients were excluded from the analysis as renal functions in these
      patients had deteriorated prior to ICS and renal failure was attributed to
      sepsis. Of the remaining 7 patients, 5 had diabetes and 2 had chronic rejection.
      Only 4 of these 7 patients with CIN received prophylaxis (I/V hydration) prior to
      ICS. The baseline serum creatinines were not different in patients who had no
      change in renal function to those who developed CIN (1.97 +/- 0.20 vs 1.54 +/-
      0.17 mg/dl, p = 1.5, mean +/- SEM). More than 50% increase in baseline serum
      creatinine was seen in only 3 of these 7 patients, 2 of these patients had
      diabetes and third had chronic rejection and congestive heart failure. None of
      these patients received prophylaxis for CIN. Dialysis was not required in any
      patient. Three patients also had a > 25% decrease in baseline serum creatinine
      after ICS, and all of them had allograft angiography with angioplasty for renal
      artery stenosis. CONCLUSION: In our retrospective study, the incidence of CIN in
      renal allograft recipients applying a broader classification of > or = 25%
      increase in baseline serum creatinine was 21.2% (7 of 33 patients). The incidence
      of CIN was lower 15.3% (4 of 26) in patients who received intravenous hydration
      compared to 42.8% (3 of 7) in patients who received no prophylaxis prior to ICS.

PMID- 10939752
TI  - Measurement of skeletal status after renal transplantation by quantitative
      ultrasound.
AB  - BACKGROUND: Osteoporosis remains a major problem following kidney
      transplantation. Radiographic measures of bone mass are of limited predictive
      value after transplantation and are complicated by preexisting renal osteopathy.
      Quantitative ultrasound (QUS) is a new and non-invasive method to assess skeletal
      status, however, no data exist on ultrasonic bone parameter after kidney
      transplantation. We evaluated the potential use of this novel method in renal
      allograft recipients and studied the accuracy compared to normal controls.
      METHOD: Thirty patients (NTP, age 47.5 +/- 13.0 years) were studied 4.8 +/- 3.2
      years after transplantation. Twenty-five healthy control persons (CON) were
      matched for age and sex. The left and right os calcis were studied by QUS and
      speed of sound (SOS) and broadband ultrasound attenuation (BUA) were measured.
      Bone stiffness (BS) was calculated from these parameters and corrected for age
      (CBS). Differences between right and left os calcis were compared to CON to
      assess the side variability. RESULTS: Mean +/- SD BS was 75 +/- 22% compared to
      young adults, age-corrected CBS was decreased in NTP with 86 +/- 25% of normal,
      indicating a two-fold increased risk of fracture. SOS was 1525 +/- 47.7 m/s, BUA
      105 +/- 22 dB/MHz. Mean difference between right and left os calcis was
      significantly higher in NTP than in CON (7.2 +/- 7.1% vs. 2.1 +/- 2.1%, p <
      0.01). Limits of agreement of the measurements (MW of differences +/- 2 SD)
      according to a Bland-Altmann-type statistic were -16.9% and 20.7%. There was no
      correlation between CBS and age, cumulative steroid dose, parathyroid hormone
      concentrations or time after transplantation. CONCLUSION: Our data show altered
      bone structure expressed by low bone stiffness values measured by quantitative
      ultrasound in kidney transplant patients. However, because of relatively high
      inter-feet variance of QUS results we suggest measurement of both ossa calcis to
      minimize measurement error after transplantation.

PMID- 10939754
TI  - Hemodialysis-induced hypoglycemia in diabetic patients.
AB  - BACKGROUND: The authors have previously reported asymptomatic hypoglycemia in non
      diabetic patients on hemodialysis. The present study was designed to assess the
      effect of hemodialysis on plasma glucose, glucagon, cortisol and catecholamines
      in diabetic patients. METHODS: Eighteen diabetic patients with chronic renal
      failure were hemodialyzed using a glucose-free dialysis fluid. They did not take
      any medication prior to dialysis and were asked not to eat during the first hour
      on hemodialysis. Blood and dialysate were sampled at regular intervals during the
      first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0
      mmol/l (72 mg/dl) in 7 of the 18 patients, below 3.5 mmol/l (63 mg/dl) in 3 and
      below 3.0 mmol/l (54 mg/dl) in one. The lowest recorded value was 2.8 mmol/l (50
      mg/dl). The mean glucose loss in the waste dialysate was 9.2 g/h. In none of the
      group of 7 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl) did
      symptoms of hypoglycemia occur. When 6 patients from this group were subsequently
      dialyzed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their
      plasma glucose became stabilized within the fasting reference range. There were
      no significant hormonal changes during the dialysis or between non-hypoglycemic
      and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may
      become hypoglycemic and not be aware of it. There is no hormonal imbalance
      causing the hypoglycemia and the hormonal response to the hypoglycemia is
      blunted. Patients with an initial plasma glucose of 5.5 mmol/l (100 mg/dl) or
      less who are hemodialyzed and who do not eat during dialysis may be particularly
      at risk, especially if they are on insulin or taking glucose-lowering medication.
      These should be dialyzed with a dialysis fluid containing at least 5.5 mmol/l
      (100 mg/dl) glucose.

PMID- 10939753
TI  - Immune response in hemodialysis patients: is there any difference when low and
      high iPTH levels are compared?
AB  - BACKGROUND: Chronic renal failure is frequently associated with secondary
      hyperparathyroidism and immunological disorders. Recent studies support the
      hypothesis that high levels of parathyroid hormone (PTH) may contribute to the
      impairment of the cellular and humoral immune response by an immunosuppressive
      effect on T- and B-cell functions. However, many studies indicate that excess PTH
      exerts a stimulatory effect on T lymphocytes. Since reports about the
      immunomodulatory effect of PTH are controversial, our aim was to compare the
      effect of low and high levels of intact PTH (iPTH) in hemodialysis patients.
      METHODS: The study was performed on 14 hemodialysis patients with high levels of
      iPTH (GI), 12 patients with low levels of iPTH (GII) and 13 volunteers (GIII),
      for whom time of dialysis, iPTH, total number of lymphocytes, B, CD4+, CD8+,
      lymphoproliferative response to phytohemagglutin (PHA), pokeweed mitogen (PWM)
      and candidin, IgG and IgM production in vitro in response to PWM, and interleukin
      (IL)-2 and IL-6 production in vitro in response to PHA were determined. RESULTS:
      Patients with high iPTH levels had significantly higher responses to PHA than
      patients with low iPTH. Lymphocyte transformation by PWM and candidin antigen was
      similar in both groups of patients, but significantly decreased when compared to
      controls. CD4+ cell counts were significantly increased in GI, and there was a
      positive correlation between the lymphoproliferative response to PHA and iPTH
      levels and CD4+ number. CONCLUSION: The present study suggests that high levels
      of iPTH in hemodialysis patients affect T-cell function, increasing the lympho
      proliferative response to PHA and the CD4+ number.

PMID- 10939755
TI  - Kinetics of the metal cations magnesium, calcium, copper, zinc, strontium,
      barium, and lead in chronic hemodialysis patients.
AB  - BACKGROUND: Dialysis patients are at risk of developing trace element imbalances.
      To further elucidate the origin of these potential trace element imbalances,
      plasma and dialysis fluids concentrations of the elements barium (Ba), calcium
      (Ca), copper (Cu), lead (Pb), magnesium (Mg), strontium (Sr) and zinc (Zn) of
      seven maintenance dialysis patients were investigated. PATIENTS AND METHODS: In
      each hemodialysis session 10 to 15 samples of each, whole blood and dialysis
      liquid before and after passing the artificial kidney were collected.
      Concentrations of elements were determined by inductively coupled plasma mass
      spectrometry following strict quality control schemes to guarantee the accuracy
      and precision of the results. RESULTS: Plasma concentrations of Cu and Zn
      continuously increased during hemodialysis. Plasma Cu remained within the
      reference range for healthy adults, whereas plasma Zn was always at or below the
      reference range in our patients. The behavior of Ca and Sr exhibited
      extraordinarily strong similarities both in plasma and dialysis liquids, although
      concentrations of Sr are approximately 2000 times lower. Plasma Ca and Sr were at
      or above the upper level of the reference range. Plasma Mg concentrations
      decreased during clinical treatment, but were at the end of dialysis still more
      than 50% higher than the high end of the reference range. Although concentrations
      of Ba in dialysis fluids were approximately 10 times lower than in plasma, plasma
      Ba concentrations (approximately 23 microg/l) were significantly elevated
      compared to plasma Ba of healthy adults. Initial concentrations of Pb in plasma
      (0.74 microg/l) were increased by approximately 15% during the clinical treatment
      and were always higher than the high limit of the reference range. Dialysis
      liquids had approximately the same Pb concentrations (0.5 to 1.3 microg/l) as
      found in the plasma of our patients but with higher concentrations at the inlet
      of the dialyzer. CONCLUSION: This study could give an insight into the kinetics
      of trace element concentrations during dialysis, the clinical relevance of which
      needs to be further elucidated.

PMID- 10939757
TI  - Pauci-immune necrotizing glomerulonephritis complicating rheumatoid arthritis.
AB  - Necrotizing glomerulonephritis associated with rheumatoid arthritis typically
      occurs in the setting of frankly apparent systemic vasculitic signs and symptoms.
      We report two recent cases that differed from this paradigm. Both patients had
      rheumatoid arthritis and deteriorating renal function due to P-ANCA positive
      pauci-immune necrotizing crescentic glomerulonephritis, but minimal systemic
      symptoms. Delay in diagnosis and institution of appropriate therapy may have
      contributed to the dialysis dependence of one of these patients. We suggest that
      heightened suspicion of an aggressive necrotizing glomerulonephritis should be
      maintained in all patients with rheumatoid arthritis who present with acute renal
      insufficiency even in the absence of frank vasculitis.

PMID- 10939756
TI  - Short-term administration of the bisphosphonate ibandronate increases bone volume
      and prevents hyperparathyroid bone changes in mild experimental renal failure.
AB  - BACKGROUND: Bisphosphonates (BP) are potent antiresorptive agents that have been
      used successfully in several bone diseases associated with hyperresorption.
      Hyperresorption, hypercalcemia, and osteoporosis are frequent findings in
      patients with renal failure or after renal transplantation. The present study was
      carried out to determine the effects of a new BP, ibandronate, on bone in a state
      of normal vs. moderately impaired renal function. MATERIAL AND METHODS: Forty 90
      day-old female rats were either 2/3 nephrectomized (Nx, n = 20) or sham-operated
      (Sham, n = 20). Half of the Nx and Sham rats received either ibandronate (1.25
      microg/rat s.c.) or vehicle once weekly for three weeks. Before euthanasia, blood
      drawings were performed and 24-hr urine was collected. Femurs were analyzed by
      bone histomorphometry. RESULTS: Serum creatinine, parathyroid hormone, and
      osteocalcin levels were equally higher in Nx rats given ibandronate or vehicle
      than in Sham rats. There was no difference in serum calcium, phosphorus, alkaline
      phosphatase, and urinary creatinine among the groups. Ibandronate-treated rats
      had lower urinary calcium and deoxypyridinoline crosslink levels than their Sham
      counterparts. Ibandronate-treated rats had higher bone volume than vehicle
      treated animals. Ibandronate prevented the increase in erosion depth and bone
      turnover in Nx rats. CONCLUSIONS: BPs such as ibandronate represent potentially
      useful tools in the treatment of certain facets of renal bone disease.
      Indications for BP therapy may include treatment of osteoporosis, hypercalcemia,
      and/or extraosseous calcifications. Optimal dose and frequency of BP
      administration need to be determined in these patients.

PMID- 10939758
TI  - Continuous veno-venous hemodiafiltration for the treatment of spontaneous tumor
      lysis syndrome complicated by acute renal failure and severe hyperuricemia.
AB  - We describe a case of Burkitt's lymphoma presenting as spontaneous tumor lysis
      syndrome (TLS) complicated by severe hyperuricemia and anuric acute renal failure
      presumed to be secondary to uric acid nephropathy. The patient was treated with
      continuous veno-venous hemodiafiltration (CVVHDF) using a dialysate flow rate of
      2.5 l/h, and a replacement fluid rate of 1.5 l/h (administered in pre-dilution).
      Mean clearances during CVVHDF for urea, creatinine, uric acid, and phosphorus
      were, respectively, 55.8 +/- 3.8, 48.9 +/- 2.6, 45.1 +/- 2.6 and 47.0 +/- 3.3
      ml/min (or 80, 70, 65 and 68 l/day, respectively). Serum urea, creatinine, uric
      acid, and phosphorus decreased from 42 to 9 mmol/l, 533 to 189 micromol/l, 1980
      to 372 micromol/l, and 2.0 to 1.4 mmol/l, respectively, after 48 hours of CVVHDF.
      Previously, we reported the use of continuous arteriovenous hemodialysis (CAVHD)
      at a high dialysate flow rate of 4 l/h for the treatment of acute renal failure
      and TLS, which provided excellent continuous clearances of small molecular weight
      solutes. This last modality was very efficient and prevented deleterious rebound
      in serum solute concentrations frequently observed in TLS after intermittent
      hemodialysis (IHD). It was concluded that high-dialysate flow rate CAVHD was a
      more potent form of treatment than conventional IHD. With recent advances in
      technology, veno-venous continuous renal replacement therapies are becoming more
      popular than arterio-venous modalities since they are safer and less cumbersome.
      Furthermore, flow rates being precisely regulated, solute clearances can be
      steadily maintained. With CVVHDF flow rates as used in this report, we achieved
      excellent solute clearances and metabolic control. We propose CVVHDF as an ideal
      treatment for acute renal failure in TLS. In our opinion, CVVHDF is an
      advantageous alternative to treat TLS complicated by acute renal failure.

PMID- 10939759
TI  - Nephropathy subsequent to hyperlipidemia.
AB  - The relationship between lipid abnormalities and the pathogenesis of renal
      disease is still unclear. Although most patients with primary hyperlipidemia do
      not develop renal function impairment, experimental and clinical data indicate a
      possible damaging effect of a disturbed lipid metabolism on the kidney. We report
      the case history of a patient with hyperlipidemia and mild nephropathy in which
      an accidentally removed kidney showed intrarenal arteriosclerosis which occured
      before the development of other cardiovascular risk factors, indicating that
      primary dyslipidemia induced nephroangiosclerosis.

PMID- 10939760
TI  - Patterns of sulfadiazine acute nephrotoxicity.
AB  - Sulfadiazine acute nephrotoxicity is reviving specially because of its use in
      toxoplasmosis in HIV-positive patients. We report 4 cases, one of them in a
      previously healthy person. Under treatment with sulfadiazine they developed
      oliguria, abdominal pain, renal failure and showed multiple radiolucent renal
      calculi in echography. All patients recovered their previous normal renal
      function after adequate hydration and alcalinization. A nephrostomy tube had to
      be placed in one of the patients for ureteral lithiasis in a single functional
      kidney. None of them needed dialysis or a renal biopsy because of a typical
      benign course. Treatment with sulfadiazine requires exquisite control of renal
      function, an increase in water ingestion and possibly the alcalinization of the
      urine. We communicate a case in a previously healthy person, a fact not found in
      the recent literature. Probably many more cases are not detected. We think that a
      prospective study would be useful.

PMID- 10939761
TI  - Metabolic acidosis during urinary retention in a patient with an enterovesical
      fistula.
AB  - We report a patient known to have an enterovesical fistula who presented severe
      acute metabolic acidosis during an episode of urinary retention. The
      enterovesical fistula which had been intermittently symptomatic for 4 years, had
      developed after several intestinal surgical procedures and related
      intraperitoneal sepsis following resection of colon cancer 21 years previously.
      The patient who had a total colectomy and ileostomy, was admitted for hip
      replacement with the routine placement of a Foley bladder catheter. Three weeks
      post-operatively, the patient developed acute urinary retention following removal
      of the urinary catheter. The output from his ileostomy was immediately markedly
      increased, presumably from bladder urine diverted into the intestines through the
      enterovesical fistula. Within a few days he presented a normal anion gap
      metabolic acidosis with raised urea and stable creatinine; his clinical status
      deteriorated markedly with profound obtundation. These metabolic abnormalities
      were readily corrected by re-insertion of the Foley catheter with restoration of
      normal urine flow and immediate corresponding fall in the ileostomy output.
      Radiographic studies showed the presence of the enterovesical fistula originating
      from the jejunum. This is the first report of acute metabolic acidosis in
      association with an enterovesical fistula; the severe metabolic disturbances were
      triggered by the development of urinary retention resulting in the diversion of
      urine into the small bowel through the fistula.

PMID- 10939762
TI  - An unexpected and serious complication of treatment with the atypical
      antipsychotic drug clozapine.
AB  - A 49-year-old man developed acute renal failure due to interstitial nephritis
      during treatment with the drug clozapine. Referral and diagnosis were delayed
      through a failure to consider complications of treatment other than neuroleptic
      malignant syndrome. Although this association has not previously been reported in
      the literature, we include details of a further 7 cases of acute renal failure in
      association with clozapine therapy reported to the Committee On Safety Of
      Medicines in the UK.

PMID- 10939763
TI  - Greater PTH suppression in dialysis patients taking sevelamer hydrochloride
      (Renagel).

PMID- 10939764
TI  - Anomalies in the anomalous: last gasp or light at last?

PMID- 10939765
TI  - Immunologic changes in healthy probands and HIV infected patients after oral
      administration of Staphylococcus aureus 12c: a pilot study.
AB  - The tumoricidal and antiviral effects of Staphylococcal toxins are well
      documented. In a preliminary study we investigated the immune modulating
      properties of these toxins by administering single oral doses of a 12c potency of
      a lysate of Staphylococcus aureus Cowan I, to 4 healthy probands and 12 HIV
      infected patients with clinical symptoms. We observed a decrease of circulating
      immune complexes in the healthy probands as well as in the HIV positive patients,
      accompanied in the latter by a significant increase of CD4 lymphocytes, CD4/CD8
      ratio and an improvement of the HIV related symptoms. None of the dose dependent
      toxic effects commonly found in Staphylococcal sepsis were noticed. Further
      research on the immune modulating effects of potencies of bacterial superantigens
      is suggested, especially in view of a possible treatment for HIV infected and
      other immune compromised patients.

PMID- 10939766
TI  - An epidemiological study of a homeopathic practice.
AB  - An analysis of 2148 consultations in a private general medical homeopathic
      practice in France was conducted in 12 periods of 7-10 days of study over four
      years. The results show that homeopathy is mainly used in mental, infectious and
      rheumatological disorders. It is suggested that homeopathy is a useful
      alternative in these illnesses, as it avoids the abuse of, and the adverse
      effects of, sedatives, antibiotics and anti-inflammatories.

PMID- 10939767
TI  - An evaluation of Coffea cruda effect on rats.
AB  - To investigate the effect of the homeopathic medicine Coffea cruda on sleep
      pattern, it was orally administered to rats at the beginning of their waking
      period. EEG from the parietal region was recorded during their next sleep cycle.
      Applying an FFT algorithm, spectral in the delta band, 0.5-2.5 Hz, was chosen as
      a marker parameter, evaluated for control and verum groups using a double-blind
      protocol. Power in the verum group was statistically higher than baseline value,
      it was not statistically different in the control group. The results indicate
      that an enhancement in EEG slow delta activity is associated with Coffea cruda.

PMID- 10939769
TI  - Discussion: the magic of non-local concepts or the chair in the Rabbi's castle.

PMID- 10939768
TI  - Magic of signs: a non-local interpretation of homeopathy.
AB  - Among homeopaths the common idea about a working hypothesis for homeopathic
      effects seems to be that, during the potentization process, 'information' or
      'energy' is being preserved or even enhanced in homeopathic remedies. The
      organism is said to be able to pick up this information, which in turn will
      stimulate the organism into a self-healing response. According to this view the
      decisive element of homeopathic therapy is the remedy which locally contains and
      conveys this information. I question this view for empirical and theoretical
      reasons. Empirical research has shown a repetitive pattern, in fundamental and
      clinical research alike: there are many anomalies in high-dilution research and
      clinical homeopathic trials which will set any observing researcher thinking. But
      no single paradigm has proved stable enough in order to produce repeatable
      results independent of the researcher. I conclude that the database is too weak
      and contradictory to substantiate a local interpretation of homeopathy, in which
      the remedy is endowed with causal-informational content irrespective of the
      circumstances. I propose a non-local interpretation to understand the anomalies
      along the lines of Jung's notion of synchronicity and make some predictions
      following this analysis.

PMID- 10939770
TI  - Madingley, Madding, Mad scenarios: an exercise in futurology.
AB  - The Madingley scenarios were created to suggest potential contrasting futures
      (around year 2020) that could develop from the same driving forces. Those
      contrasting futures are named 'Trust their Guidance' and 'Find my Way',
      respectively. Trust their Guidance depicts a world where institutions have
      succeeded in adapting to the changing world and have strengthened their power and
      control on nations. Find my Way depicts a world where empowered individuals have
      taken responsibility for optimising their own lives. The discussion of these
      scenarios raised a number of questions including the purpose and role of
      governments, differences between societies, fundamental vs superficial change
      and, applied to the area of homeopathy, the role and responsibility of the
      homeopathic community in shaping the future of this medical approach.

PMID- 10939771
TI  - Effects of potentization.

PMID- 10939772
TI  - Effects of potentization.

PMID- 10939773
TI  - What research is needed to show the effectiveness of homeopathy?
AB  - Using the similia principle, the classical homeopath tries to find a substance
      that fits the patients complaints as closely as possible. Unusual symptoms that
      do not fit the symptom complexes recognised by conventional medicine may be
      considered even more important than the regular symptoms. This is why homeopathy
      is a highly individualised treatment, resulting in different treatments for
      patients who would receive an identical treatment in conventional medicine.

PMID- 10939774
TI  - The Madingley scenarios for the future context of healthcare: understanding today
      by imagining tomorrow.

PMID- 10939775
TI  - International integrative primary care outcomes study (IIPCOS-2): an
      international research project of homeopathy in primary care.
AB  - OBJECTIVE: The primary objective is to evaluate the effectiveness of homeopathic
      treatment compared to conventional treatment for respiratory and ear complaints
      commonly seen in the primary care setting: runny nose, sore throat, ear pain,
      sinus pain, and cough. METHOD: This study is an international, multi-center,
      prospective, outcomes study on the effectiveness of homeopathic treatment
      compared to conventional treatment. The participating investigators will be
      divided into three groups: * Homeopathic treatment; * Homeopathic or conventional
      treatment according to the patient's preference, either randomized or non
      randomized; * Conventional treatment. A total of 2400 patients will be recruited.
      Consecutive patients, age one month or older, presenting with one of the five
      chief complaints, and onset of symptoms less than seven days will be included
      into the study. Prior to enrolment into the trial each patient must provide
      written informed consent. Patient outcome will be measured using the Integrative
      Medicine Outcomes Scale (IMOS) at 7-, 14- and 28-d telephone follow-up. In
      addition, covariate data related to the following will be collected: patient
      demographics and medical history, patient preference for treatment and
      willingness to be randomized, health-related quality of life, primary treatment
      and adjunctive therapies prescribed, adverse events, type and length of
      consultation, follow-up recommendation, patient compliance, patient satisfaction
      with treatment, and patient willingness to choose therapy and health care
      provider again. The main outcome criterion will be the response rate according to
      the IMOS after 14 days of treatment. RESULTS: Preliminary interim results will be
      presented. CONCLUSIONS: Lessons learned from the study will be discussed.

PMID- 10939776
TI  - Using a computer-based clinical management system to improve effectiveness of a
      homeopathic service in a fundholding general practice.
AB  - Problems which the development attempts to address. This study's overall
      objectives were to determine whether: * The aims of collaboration between General
      Practitioner (GPs) and a homeopath can be made explicit and service delivery
      optimised by using computer-based data collection in a multi-disciplinary primary
      care team that includes a homeopathic practitioner. * Outcomes of the homeopathic
      service can be evaluated in a practical way, which allows quality assurance
      through rapid audit cycles. METHOD: The primary care team (PCT) explored the
      problems of developing a rational and quality assured complementary therapy
      service in a series of meetings in an NHS practice where complementary therapists
      are members of the PCT. This led to the defining of data-collection structures
      and processes needed. The researchers designed and supervised their
      implementation and evaluation through a series of action research cycles. A
      database was designed which allowed the clinicians to track interventions and
      outcomes using the Measure Your Own Medical Outcome Profile (MYMOP). Critical
      incidents were brought to fortnightly clinical meetings and methods were
      continually adapted as problems arose and new options emerged at six-weekly audit
      meetings. RESULTS: GPs tended to refer patients who do not fit easily into
      biomedical disease categories. Patients referred tend to self-rate themselves as
      experiencing notably poor wellbeing. MYMOP has to be used skillfully with
      homeopathic patients, especially where psychological distress is identified as
      one of their main complaints. CONCLUSIONS: It is possible to introduce rigour and
      reflectiveness when providing a homeopathic service in general practice by
      assessing the needs of patient and practitioners, agreeing intake guidelines,
      developing referral processes, implementing audit cycles. Clear lines of
      communication can be established and a patient-centred outcome measure can be
      introduced into the treatment cycle.

PMID- 10939777
TI  - Assessing the cost-effectiveness of homeopathic medicines: are the problems
      different from other health technologies?

PMID- 10939778
TI  - The economic evaluation of complementary medicine: a staged approach at the Royal
      London Homeopathic Hospital.
AB  - OBJECTIVE: The practical implementation of a staged, multifaceted research agenda
      for the economic evaluation of complementary medicine (CM) at the Royal London
      Homeopathic Hospital (RLHH). METHOD: The relative importance of economic
      evaluation as an evidence base of CM was assessed via a survey conducted with
      purchasers (n=481). The marginal costs of providing complementary care for
      patients with rheumatoid arthritis were calculated. The use, and changes in the
      use, of conventional medicines for patients' main complaints were established
      retrospectively (n=499) and prospectively (n=70). Health-related quality of life
      (patient utility) of newly referred patients was assessed with the EQ-5D
      (EuroQol) instrument (n = 70) on a 100 mm (0 = worst, 100 = best) scale. RESULTS:
      Economic evaluation was rated 'important' as an evidence base, after safety and
      RCT data ('very important'). Consultation time (doctors and dietician)
      contributed 29% of the total costs of treating rheumatoid arthritis. The
      retrospective survey showed that many patients on conventional medication were
      able to stop (29%) or reduce (32%) intake in the course of treatment. The median
      (quartiles) health state of newly referred patients was 70 mm (50,78) in men and
      60 mm (36,73) in women. Some results of an interim analysis of 6 months follow-up
      data are reported. CONCLUSIONS: Economic evaluation of CM is becoming
      increasingly important and should take place by using a multifaceted, staged
      approach. Before embarking on randomised trials, observational data on cost,
      effectiveness and utility should be collected. The cost-effectiveness of CM
      appears to be most sensitive to the duration of the consultation.

PMID- 10939779
TI  - Improving the evaluation of homeopathy: economic considerations and impact on
      health.
AB  - OBJECTIVES: The financial crisis of health insurance systems sometimes drives
      public policy-makers to take precipitate action dominated by economic
      imperatives. The question addressed here consists in defining homeopathy's scope
      of intervention, its place in health care strategies, recourse to treatment, and
      especially economic data appraising homeopathy's impact on expenditures and
      outlay covered by health insurance in France. METHOD: We used the General
      Evaluation Model to define the study (to whom is the evaluation made, situations,
      criteria, measurement of these criteria, quality and precision). RESULTS: The
      main results are in terms of costs, as follows: * For reimbursable medicines the
      public sales price of homeopathic products is a quarter of the average. * The
      total reimbursement for a prescription of allopathic products is three times more
      than for a prescription of homeopathic products. * Homeopathic physicians incur
      annual reimbursement outlays which are half those of general practitioners. The
      differences observed cannot be explained by the patient profile or the diseases
      treated. Furthermore, a study carried out in France showed that 87% of patients
      whose physicians had prescribed homeopathic treatment did not see another
      physician for the same problem. CONCLUSIONS: Once basic analysis has been done,
      so that the economic and epidemiological impact of a certain health strategy can
      be determined, it is necessary to proceed further, helping healthcare providers
      and public authorities to make decisions. Various possibilities exist and should
      be investigated.

PMID- 10939780
TI  - Effects of acupuncture and homeopathy: prospective documentation. Interim
      results.
AB  - OBJECTIVE: To evaluate the overall effectiveness in general practice of
      homeopathy and acupuncture, and to estimate costs. METHOD: Prospective
      documentation of all patients insured with an insurance company who are provided
      with free treatment of acupuncture and homeopathy. 4000 patients treated by
      acupuncture and 1000 patients by homeopathy will be enrolled. All patients will
      be followed up from the beginning of treatment for another 4 years. Doctors will
      provide data on each visit (diagnosis, treatment, change of symptoms, etc.),
      patients will fill in questionnaires at the beginning and at the end of
      treatment, as well as each year after the end of treatment (complaints, current
      treatment, general health status as measured by the MOS-SF 36). Insurance data on
      workdays lost will be provided by the insurance company. RESULTS: Data
      acquisition and entry is continuing. Up to now data from the first questionnaire
      of 1453 patients have been entered and 951 patients have returned the follow-up
      questionnaire. Doctors' ratings of the change of the main diagnosis shows
      improvement of around 80% with only 2% deteriorated. This impression is
      vindicated by the patients' follow-up questionnaire. 36% patients rated the
      therapy as efficacious, 47% as partially efficacious. Quality of life as measured
      by the SF 36 questionnaire improved significantly in all dimensions. Data on
      workdays off will be presented. CONCLUSION: Homeopathy and acupuncture are
      clinically effective in a variety of medical problems.

PMID- 10939781
TI  - Do homeopathic medicines provoke adverse effects? A systematic review.
AB  - OBJECTIVE: To evaluate the safety of homeopathic medicines by critically
      appraising reports of adverse effects published in English from 1970 to 1995.
      METHOD: Systematic review on information regarding adverse effects of homeopathic
      medicines identified using electronic databases, hand searching, searching
      reference lists, reviewing the bibliography of trials, and other relevant
      articles, contacting homeopathic pharmaceutical companies and drug regulatory
      agencies in UK and USA, and by communicating with experts in homeopathy. RESULTS:
      The mean incidence of adverse effects of homeopathic medicines was greater than
      placebo in controlled clinical trials (9.4/6.1) but effects were minor, transient
      and comparable. There was a large incidence of pathogenetic effects in healthy
      volunteers taking homeopathic medicines but the methodological quality of these
      studies was generally low. Anecdotal reports of adverse effects in homeopathic
      publications were not well documented and mainly reported aggravation of current
      symptoms. Case reports in conventional medical journals pointed more to adverse
      effects of mislabelled 'homeopathic products' than to true homeopathic medicines.
      CONCLUSIONS: Homeopathic medicines in high dilutions, prescribed by trained
      professionals, are probably safe and unlikely to provoke severe adverse
      reactions. It is difficult to draw definite conclusions due to the low
      methodological quality of reports claiming possible adverse effects of
      homeopathic medicines.

PMID- 10939782
TI  - Blood pressure burden: vascular changes and cerebrovascular complications.

PMID- 10939783
TI  - Reducing the global burden of blood pressure-related cardiovascular disease.
AB  - OBJECTIVE: To assist in prioritisation for strategies for the control of
      cardiovascular disease (CVD) worldwide, by estimating the size of the
      contribution of elevated blood pressure and, more importantly, the likely effects
      of its modification. DESIGN: We estimated the size of the disease burden
      attributable to increased blood pressure in Eastern Asia and describe a method
      for estimating the likely effects of blood pressure lowering strategies. METHODS:
      Attributable risk estimates were calculated to assess the likely contribution of
      increased blood pressure to death from CVD in Asia. Estimates were also made of
      the possible effects of population-wide (2% lower diastolic blood pressure [DBP]
      for all) and targeted (7% lower DBP for those with DBP > or =95 mm Hg) blood
      pressure lowering interventions. These estimates were based on data from several
      sources, including surveys of blood pressure values in Asian populations,
      estimates of the incidence of cardiovascular disease in Asia, studies of the
      associations of blood pressure with cardiovascular disease risks in Asia and
      elsewhere, and randomized trials of blood pressure lowering treatments. RESULTS:
      The results suggest that DBP values of 80 mm Hg or more account for about 57% of
      all stroke deaths and about 24% of all coronary heart disease deaths in Eastern
      Asian populations. The two intervention strategies proposed would each be
      expected to avert about 1 in 6 stroke deaths and about 1 in 20 coronary heart
      disease deaths. This would amount to about 1 million deaths per year throughout
      Asia by 2020, with about half of those deaths averted in the People's Republic of
      China. The benefits of the two different approaches would be approximately
      additive. CONCLUSIONS: Increased blood pressure levels are directly responsible
      for the majority of stroke deaths (more than 50%) and a substantial minority of
      deaths from coronary heart disease (about 25%) in Eastern Asia. Both modest
      population-wide blood pressure reductions and more moderate targeted reductions
      in those with hypertension could be expected to produce large reductions in the
      burden of cardiovascular disease in these and other Asian regions.

PMID- 10939784
TI  - Effects of angiotensin-converting enzyme inhibitors on cerebral vascular
      structure in chronic hypertension.
AB  - Chronic hypertension profoundly alters the function and structure of cerebral
      blood vessels. Cerebral arterioles undergo remodelling, with a reduction in
      external diameter and hypertrophy of the vessel wall and a paradoxical increase
      in distensibility. The primary aim of this review is to consider recent findings
      in relation to determinants of remodelling, hypertrophy, and altered
      distensibility and composition of cerebral blood vessels during chronic
      hypertension, with an emphasis on the renin-angiotensin system. In particular, we
      highlight studies designed to examine the hypothesis that the effects of
      angiotensin-converting enzyme (ACE) inhibitors on cerebral vascular structure in
      stroke-prone spontaneously hypertensive rats (spSHR) may be independent of their
      effects on reductions in arterial pressure. For example, treatment of spSHR with
      the ACE inhibitor perindopril attenuates remodelling of cerebral arterioles, even
      when given in a low dose that only partially normalizes systemic arterial
      pressure and does not prevent hypertrophy. In contrast, treatment of spSHR with
      propranolol does not prevent cerebral arteriolar remodelling, even when given in
      a dose that produces a larger decrease in blood pressure than is achieved with
      the low dose of perindopril. Results such as these suggest that remodelling of
      cerebral arterioles during chronic hypertension may be independent of increases
      in arterial pressure, and instead may depend primarily on increased activity of
      the renin-angiotensin system. Evidence is also reviewed that suggests that the
      renin-angiotensin system may not contribute significantly to hypertrophy of
      cerebral arterioles during chronic hypertension. Rather, hypertrophy appears to
      depend in large part on increases in arterial pressure and, in particular, its
      pulsatile component.

PMID- 10939785
TI  - PROGRESS (Perindopril Protection Against Recurrent Stroke Study): regional
      characteristics of the study population at baseline. PROGRESS Management
      Committee.
AB  - OBJECTIVE: To determine the effects of an angiotensin-converting enzyme (ACE)
      inhibitor-based blood pressure lowering regimen on the risk of stroke among
      patients with a history of cerebrovascular disease. Secondary aims include
      investigation of the effects of treatment on other cardiovascular events,
      dementia, and disability. DESIGN AND METHODS: PROGRESS (Perindopril Protection
      Against Recurrent Stroke Study) is a double-blind, placebo-controlled, randomized
      trial being conducted in 172 centres in 10 countries (Australia, Belgium, China,
      France, Italy, Ireland, Japan, New Zealand, Sweden, and the United Kingdom).
      Patients were randomly assigned to treatment with the ACE inhibitor perindopril
      (and the diuretic indapamide for those with no definite indication for or
      contraindication to treatment with a diuretic) or matching placebo(s). Both
      hypertensive and normotensive patients were eligible for inclusion. Follow-up is
      scheduled for completion in 2001. RESULTS: Of 6105 patients randomly allocated to
      study groups on completion of recruitment in November 1997, 1110 were recruited
      from Australia and New Zealand, 1520 from China, 713 from France and Belgium, 557
      from Italy, 815 from Japan, 675 from Sweden, and 715 from the UK and Ireland.
      Regional differences in the baseline characteristics included a greater rate of
      diabetes, lacunar infarction, and cerebral haemorrhage in patients from China and
      Japan, and a more frequent history of myocardial infarction in Australia and New
      Zealand. Previous treatment with calcium antagonists was very frequent in Japan
      and China, whereas diuretic treatment was most often documented in the UK and
      Ireland. CONCLUSIONS: Analysis of baseline characteristics of patients recruited
      from seven distinct geographic regions revealed some interesting differences, but
      more striking was the consistency of characteristics of patients recruited from
      many different countries across the world.

PMID- 10939786
TI  - Blood pressure reduction and risk of dementia in patients with stroke: rationale
      of the dementia assessment in PROGRESS (Perindopril Protection Against Recurrent
      Stroke Study). PROGRESS Management Committee.
AB  - High blood pressure is a known risk factor for multi-infarct dementia, a subtype
      of dementia caused by the occurrence of several strokes. However, this form of
      dementia is relatively uncommon and the influence of blood pressure on the risk
      of other subtypes of vascular dementia remains to be clarified. Furthermore,
      recent studies have suggested that vascular risk factors could also play a part
      in Alzheimer's disease. One of the aims of Perindopril Protection Against
      Recurrent Stroke Study (PROGRESS) is to test the hypothesis that blood pressure
      decreasing treatment based on perindopril would reduce the incidence of dementia
      among patients with cerebrovascular disease. The dementia procedures in PROGRESS
      involve a classical two-phase design, with an initial screening phase based
      mainly on the Mini-Mental State Examination - a simple, brief, and widely used
      screening test for dementia. The second phase involves a diagnostic assessment
      for dementia in individuals screened as positive according to the criteria of the
      American Psychiatric Association's Diagnostic and statistical manual of mental
      disorders (4th ed.). In this project, two other domains of the relationship
      between vascular risk factors and cognition are being explored in relation to
      PROGRESS substudies. The apolipoprotein E polymorphism, a genetic risk factor for
      Alzheimer's disease, is being determined in each patient, as part of the genetic
      substudy. This will allow study of the relationship between this polymorphism and
      blood pressure, and of the effect of blood pressure decreasing treatment on the
      risk of dementia. The magnetic resistance imaging substudy will improve
      understanding of the relationship between blood pressure decreasing and the
      occurrence of cerebral white matter lesions, which are known to be related to
      cognitive decline and dementia.

PMID- 10939787
TI  - Lipids on the move: phosphoinositide 3-kinases in leukocyte function.

PMID- 10939788
TI  - [Proceedings of the International Symposium on Social Inequalities and Health.
      Italy, 1 June 1999].

PMID- 10939789
TI  - What role for transjugular intrahepatic portosystemic shunt?

PMID- 10939791
TI  - British Cancer Research Meeting 2000. Brighton, United Kingdom, 9-12 July 2000.
      Abstracts.

PMID- 10939790
TI  - Career pathways.

PMID- 10939792
TI  - Ischemic right heart failure following LVAD implantation.

PMID- 10939793
TI  - Caring for heart transplant patients suggestion for a new communication tool.

PMID- 10939794
TI  - Characteristics of hydrogen ion transport in urinary bladder of water turtle.

PMID- 10939795
TI  - [Percutaneous interstitial radiofrequency ablation with a "cluster" ablation
      probe].

PMID- 10939797
TI  - Homogeneous expression of CXC chemokine receptor 4 (CXCR4) on G-CSF-mobilized
      peripheral blood CD34+ cells.

PMID- 10939796
TI  - Translocation t(11;18) absent in early gastric marginal zone B-cell lymphoma of
      MALT type responding to eradication of Helicobacter pylori infection.

PMID- 10939798
TI  - High incidence of symptomatic cytomegalovirus infection in multiple myeloma
      patients undergoing autologous peripheral blood stm cell transplantation.

PMID- 10939799
TI  - PCR-detectable transcripts in long-term remission of P190(BCR/ABL)-positive acute
      lymphoblastic leukemia.

PMID- 10939800
TI  - Lack of SH3 domain does not imply a more severe clinical course in Ph+ chronic
      myeloid leukemia patients.

PMID- 10939801
TI  - Levels of circulating CD19+ cells in patients with multiple myeloma.

PMID- 10939802
TI  - Cytomegalovirus infection and disease after autologous CD34-selected peripheral
      blood stem cell transplantation for multiple myeloma: no evidence of increased
      incidence based on polymerase-chain-reaction monitoring.

PMID- 10939803
TI  - Myocardial ischemia following allogeneic bone marrow transplantation: possible
      implication of tacrolimus overdose.

PMID- 10939804
TI  - Differences between refractory anemia with excess blasts in transformation and
      acute myeloid leukemia.

PMID- 10939805
TI  - Clinical manifestations, management, and molecular genetics in congenital factor
      VII deficiency: the International Registry on Congenital Factor VII Deficiency
      (IRF7)

PMID- 10939806
TI  - No germline ATM mutation in a series of 16T-cell prolymphocytic leukemias.

PMID- 10939807
TI  - Expression of unmutated VH genes is a detrimental prognostic factor in chronic
      lymphocytic leukemia.

PMID- 10939808
TI  - Environmental biotechnology. Towards sustainability.

PMID- 10939809
TI  - Commentary: an open debate is not an admission of failure.

PMID- 10939810
TI  - Is CS spray dangerous. Formulation affects toxicity.

PMID- 10939811
TI  - Is CS spray dangerous? CS is a particulate spray, not a gas.

PMID- 10939812
TI  - Effects of multiple courses of antenatal steroids are uncertain.

PMID- 10939813
TI  - Is CS spray dangerous? Hazards are being hidden.

PMID- 10939814
TI  - Patient information on cancer. Access to the information should be made easier.

PMID- 10939815
TI  - Patient information on cancer. Newspaper read is good predictor of information
      needs.

PMID- 10939816
TI  - Changing face of refractive surgery.

PMID- 10939817
TI  - Radiosensitive tissues can be shielded during CT scanning.

PMID- 10939818
TI  - Behavioural counselling in general practice about risk of CHD. Study was grossly
      underpowered.

PMID- 10939819
TI  - Behavioural counselling in general practice about risk of CHD. Study had several
      methodological flaws.

PMID- 10939821
TI  - Brave new technologies issue. Clever technology looking for a purpose.

PMID- 10939820
TI  - Behavioural counselling in general practice about risk of CHD. Non-attendance for
      follow up distorts results and shows that people don't like counselling.

PMID- 10939822
TI  - Brave new technologies issue. On a road to nowhere.

PMID- 10939823
TI  - Brave new technologies issue. Sad example of inappropriate use of new
      technologies in publishing.

PMID- 10939824
TI  - Brave new technologies issue. Someone should be sacked.

PMID- 10939826
TI  - Brave new technologies issue. Revolutionary delivery and management of
      information.

PMID- 10939825
TI  - Brave new technologies issue. Support from the future.

PMID- 10939827
TI  - Brave new technologies issue. Snoozing with the journal may not be informative.

PMID- 10939828
TI  - Brave new technologies issue. Step towards doing medicine with people rather than
      for or to them.

PMID- 10939829
TI  - Acute medicine needs to be available 365 days a year.

PMID- 10939830
TI  - Burns after photodynamic therapy: manufacturer's response to second authors'
      reply.

PMID- 10939831
TI  - Optimum treatment for young women with breast cancer needs to be determined.

PMID- 10939832
TI  - Columnar organization of nitric oxide synthase (NOS) in the prefrontal cortex of
      primates.

PMID- 10939833
TI  - Complexity of lifting.

PMID- 10939835
TI  - Apology. Evaluations in mental health services: some methodological
      considerations.

PMID- 10939834
TI  - [Internet resources on electron microscopy].

PMID- 10939836
TI  - [Modalities of mechanical ventilation].
AB  - Mechanical ventilation improves the symptoms and reduces complications of acute
      respiratory failure. Recent advances in microprocessor technology have increased
      the sophistication of mechanical ventilators, thus leading to new ventilation
      modalities. This article describes the ventilation modalities available, grouping
      them as conventional, alternative and new modalities. Conventional ventilation
      includes the most widely used modalities, alternative ventilation includes less
      frequently used modalities, and new ventilation modalities include recently
      introduced options that are available on the latest-generation mechanical
      ventilators.

PMID- 10939837
TI  - The fruits of the fly genome project.

PMID- 10939838
TI  - Meningococcal genomics - decoded at last?

PMID- 10939839
TI  - 'Lymphochips' and cancer profiles.

PMID- 10939840
TI  - Clues to the cause of neurodegeneration.

PMID- 10939841
TI  - Repetitive strain.

PMID- 10939842
TI  - Obesity and diabetes: an avalanche of new information.

PMID- 10939843
TI  - Chromosomal aberrations detected after stimulation with lipopolysaccharide in a
      patient with Asian variant intravascular lymphomatosis.

PMID- 10939844
TI  - First Japanese case of sole trisomy 13 anomaly in acute myeloid leukemia.

PMID- 10939845
TI  - Cytogenetics of thyroid nodules in Hashimoto thyroiditis.

PMID- 10939846
TI  - Carbapenem-resistant Pseudomonas aeruginosa with acquired bla(vim) metallo-beta
      lactamase determinants, Italy.

PMID- 10939847
TI  - High production of ginsenosides by transformed root cultures of Panax ginseng:
      effect of basal medium and Agrobacterium rhizogenes strains.
AB  - Successful transformation of Panax ginseng was achieved when petiole segments
      were infected with Agrobacterium rhizogenes ATCC 15834 and MAFF 03-01724.
      Transformed roots were obtained after galls developed at infected sites. The root
      morphology, growth and ginsenoside productivity of roots transformed with
      different bacterial strains differed, and the roots from A. rhizogenes ATCC 15834
      grew better and produced much more ginsenosides. Using the ATCC transformed root
      clone, various liquid culture media were tested to determine the optimum culture
      medium for ginsenoside production. The root growth was optimum in phytohormone
      free Gamborg B5 liquid medium, however highest content of ginsenosides (a total
      of five ginsenosides 1.88% dry weight) was obtained when the roots were cultured
      in half-macro-salt strength Gamborg B5 liquid medium. Growth of the roots over a
      period of 8 weeks showed that their fresh and dry weight continued to increase.
      The ginsenoside Rb1 content was optimum after 5 weeks of culture. Ginsenoside Rc
      content began to decrease slightly after the third week of culture. Ginsenosides
      Rd and Rg1 contents fluctuated, while ginsenoside Re content continued to rise
      throughout the 8 weeks of culture. Ginsenoside production, however, did not peak
      within the 8 weeks of culture.

PMID- 10939848
TI  - [Studies on simultaneous determination of 17 organochlorine and 9 pyrethroid
      pesticides of agricultural products].
AB  - A method for simultaneous determination of 17 organochlorine and 9 pyrethroid
      pesticides in agricultural products by capillary GC with ECD detection was
      studies. The samples were extracted with acetone under acidic conditions followed
      by Florisil column clean-up and then injected into a GC-ECD. The organochlorine
      pesticides used in this study included unstable captan and captafol in the
      homogenized preparations of fruits and vegetables. Captan and captafol were also
      found to decompose in rice and wheat samples when the samples were allowed to
      stand after the addition of water. Addition of phosphoric acid to the samples was
      effective in preventing the decomposition of captan and captafol. Recovery of the
      pesticides investigated in this study was not decreased by the addition of
      phosphoric acid. Addition of phosphoric acid was also effective in removing
      interfering substances from onion extract. Recovery of organochlorine and
      pyrethroid pesticides from samples spiked at levels of 0.05-0.25 ppm by the
      proposed method was 51.4-100.8% for rice and wheat and 60.1-119.0% for
      vegetables.

PMID- 10939849
TI  - [Computational study on antioxidation mechanism of catechins].
AB  - All C-H and O-H bond dissociation enthalpies (BDE's) in catechins, (-)
      epigallocatechin) were calculated by semi-empirical molecular orbital calculation
      using the SPARTAN program. The BDE's of benzyl hydrogens (C-2 position in
      catechins) were found to be quite low. This suggests that abstraction of benzyl
      hydrogen is crucial step for antioxidative activity. This is corroborated by the
      reported results of LC/MS and spectrophotometric analysis of reaction
      intermediates from catechins treated with AAPH.

PMID- 10939850
TI  - [Molecular mechanics study on Conformation of a homooligopeptide constituted by
      isovalin].
AB  - Conformational energy computations on a homo-hexapeptide of (S)-isovaline were
      performed using molecular mechanics on MacroModel. Conformational search
      calculations were carried out by Monte Carlo method. AMBER* was used as the force
      field. The global minimum energy conformation was found to be a 3(10)-helix
      coordinated by four hydrogen bonds. The results of the theoretical analysis of
      the conformation of the peptide are in agreement with its reported conformational
      properties in the solid state determined by X-ray crystallographic analysis.

PMID- 10939851
TI  - [Inspection of undesignated food color in imported chewing gum].
AB  - An unknown color in chewing gum imported from Canada was determined. The color
      was identified by TLC and HPLC as the trisodium salt of 3-hydroxy-4[(4
      sulfopheny)azo]-2,7-naphthalenedisulfonic acid (RS-SA), one of the subsidiary
      colors of sunset yellow FCF. The concentration of RS-SA in sunset yellow FCF used
      in the chewing gum was 4.3%

PMID- 10939852
TI  - [Preparation of the database and the Internet (WWW) homepage for regulations on
      chemicals in Japan].
AB  - We prepared a database on chemical regulations in Japan. The regulations consist
      of "The Law concerning the Examination and Regulation of Manufacture, etc., of
      Chemical Substances", "Poisonous and Deleterious Substances", Control Law",
      "Waterworks Law", "Law for the Control of Household Products containing Harmful
      Substances", and Pesticide Residues in Food Sanitation Law". We also set up a
      World Wide Web (WWW) homepage containing an explanation of the law as well as
      chemical names, CAS registry numbers, and standards. The WWW pages contain lists
      of chemicals and the retrieval page for the database.

PMID- 10939853
TI  - [First drafts of the Environmental Health Criteria (EHC) circulated for comments
      by IPCS in 1998.41999.3].
AB  - Summaries of the first draft Environmental Health Criteria (EHC) circulated for
      comments by IPCS during the period of 1998.4  1999.3 are presented. EHC drafts on
      3 compounds were received during this period.

PMID- 10939854
TI  - [Studies on rejected food yellow No. 5 (sunset yellow FCF)].
AB  - One of the sunset yellow FCFs (Y-5) in the official inspection of coal-tar dyes
      in 1998 was rejected. The results of tests of the rejected sample were submitted
      to JSFA-VI except for a sub-spot by paper chromatography. HPLC of the raw
      materials, intermediates, and subsidiary dyes according to JSFA-VII was performed
      on the rejected and submitted samples of Y-5. The sub-spot in the rejected sample
      was identified as sulfanilic acid-azo-R salt, and its content was estimated at
      more than 5%.

PMID- 10939855
TI  - [Estimated production by the official inspection of coal-tar dyes (including dye
      aluminum lakes) in fiscal year 1998].
AB  - There were 284 official inspections of coal-tar and their lakes in fiscal year
      1998, and 283 of the lots qualified, one of the 40 samples of Food Yellow No. 5
      was rejected. The quality of coal-tar dyes that passed inspection in Japan in
      fiscal year 1998 reached 150.3 tons. Coal-tar dye production is summarized by
      manoth in Table 2 and by manufacturer in Table 3. The food coal-tar dye produced
      in the largest quantity was Food Yellow No. 4, accounting for 44.1% during this
      period.

PMID- 10939856
TI  - [Digoxin Reference Standard (Control 991) of National Institute of Health
      Sciences].
AB  - The raw material of digoxin was examined to prepare a "Digoxin Reference
      Standard". The analytical data obtained were: optical rotation, [alpha](20)D = +
      11.7 degree; loss on drying, 0.008%, infrared spectrum, the same as that of the
      Digoxin Reference Standard (Control 807); high-performance liquid chromatography,
      several impurities detected and the total amount estimated to be about 0.31%,
      assay by spectrophotometry, 100.1%. Based on the above results, the candidate
      material was authorized as the Digoxin Reference Standard (Control 991) of the
      National Institute of Health Sciences.

PMID- 10939857
TI  - [Lanatoside C Reference Standard (Control 981) of National Institute of Health
      Sciences].
AB  - The raw material of lanatoside C was examined for preparation of the "Lanatoside
      C Reference Standard". The analytical data obtained were: melting point, 247.4
      degree C; optical rotation, [alpha]20(D) = + 34.0 degree, loss on drying, 6.93%;
      infrared spectrum, the same as that of the Lanatoside C Reference Standard
      (Control 784); thin-layer chromatography, two impurities detected; high
      performance liquid chromatography, several impurities detected and the total
      amount estimated to be about 1.26%; assay by spectrophotometry, 103.0%. Based on
      the above results, the candidate material was authorized as the Lanatoside C
      Reference Standard (Control 981) of the National Institute of Health Sciences.

PMID- 10939858
TI  - [Glycyrrhizic Acid Reference Standard (Control 991) of National Institute of
      Health Sciences].
AB  - The raw material of glycyrrhizic acid examined for preparation of the
      "Glycyrrhizic Acid Reference Standard". The analytical data obtained were: UV
      spectrum: Lambda max, 251 nm; specific absorbance (E (1%) 1cm) in ethanol at 251
      nm, 146; IR spectrum, specific absorptions at 1716,1656, 1215, and 1170 cm-1; and
      the spectrum of raw material was consistent with that of Standard (Control 941).
      Also, thin-layer chromatography, no impurities detected; high-performance liquid
      chromatography, three impurities detected. The amount of each impurity was
      estimated at less than 0.1%, and the total amount of impurities was less than
      0.2%. Based on the above results, the candidate material was authorized as the
      Glycyrrhizic Acid Reference Standard (Control 991) of the National Institute of
      Health Sciences.

PMID- 10939859
TI  - [Tocopherol Succinate Reference Standard (Control 981) of National Institute of
      Health Sciences].
AB  - The raw material of tocopherol succinate was tested for preparation of the
      "Tocopherol Succinate Reference Standard (Control 981)". The analytical data
      obtained were: infrared spectrum same as that of the Tocopherol Succinate
      Reference Standard (Control 8510); specific absorbance, E(1%)1 cm (286 nm) =
      40.7; thin-layer chromatography, no impurities detected until 50.0 microgram;
      high-performance liquid chromatography (HPLC),three impurities detected and
      amount of tocopherol succinate estimated to be 98.2%, loss on drying, 0.19%,
      assay by HPLC, 101.7%. Based on the above results, the raw material was
      authorized as the Japanese Pharmacopoeia Reference Standard (Control 981).

PMID- 10939860
TI  - [Fluocinolone Acetonide Reference Standard (Control 981) of National Institute of
      Health Sciences].
AB  - The raw material of fluocinolone acetonide was examined for preparation of the
      "Fluocinolone Acetonide Reference Standard (Control 981)". The analytical data
      obtained were: melting point, 271.5 degree C; UV spectrum, Lambda max of 237.0 nm
      and specific absorbance in ethanol at 237 nm of 359.3; IR spectrum, same as that
      of the Fluocinolone Acetonide Reference Standard (Control 904); optical rotation,
      [alpha]20(D) = + 102.8; thin-layer chromatography, no impurities detected; high
      performance liquid chromatography, one impurity detected and total amount
      estimated to be about 0.17%; loss on drying, 0.29%; assay by HPLC, 100.9%. Based
      on the above results, the raw material was authorized as the Fluocinolone
      Acetonide Reference Standard (Control 981) of the National Institute of Health
      Sciences.

PMID- 10939861
TI  - [Fluocinonide Reference Standard (Control 981) of National Institute of Health
      Sciences].
AB  - The raw material of fluocinonide was examined for preparation of the
      "Fluocinonide Reference Standard (Control 981)". The analytical data obtained
      were: UV spectrum, lambda max of 237.4 nm; IR spectrum, same as that of the
      Fluocinonide Reference Standard (Control 841); optical rotation, [alpha]20(D) = +
      84.4 degree, thin-layer chromatography, one impurity detected; high-performance
      liquid chromatography, three impurities detected and total amount estimated to be
      about 0.20%; loss on drying, 0.15%; assay by HPLC, 99.6% Based on the above
      results, the raw material was authorized as the Fluocinonide Reference Standard
      (Control 981) of the National Institute of Health Sciences.

PMID- 10939862
TI  - Guess what! Diagnosis: granuloma faciale.

PMID- 10939863
TI  - Guess what! Diagnosis: Extended ulcerating metatypical basal cell carcinoma (BCC)
      with soft tissue and bone destruction.

PMID- 10939864
TI  - Modified standard (D1 + alpha) pancreaticoduodenectomy for pancreatic cancer.

PMID- 10939865
TI  - Extent of lymphadenectomy in the surgical treatment of adenocarcinoma of the head
      of the pancreas.

PMID- 10939866
TI  - The Johns Hopkins experience with pancreaticoduodenectomy with or without
      extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma.

PMID- 10939867
TI  - Paper alert. Plant biology.

PMID- 10939868
TI  - Web alert. Biotic interactions.

PMID- 10939869
TI  - Biotic interactions. Genomics and coevolution.

PMID- 10939870
TI  - Extracorporeal shock wave lithotripsy of renal calculi during early pregnancy.

PMID- 10939871
TI  - The role of urine cytology in the assessment of lower urinary tract symptoms.

PMID- 10939872
TI  - Asymptomatic inflammation and/or infection in benign prostatic inflammation.

PMID- 10939874
TI  - Incidental renal carcinoma with renal calculus disease: a series of five cases.

PMID- 10939873
TI  - A novel technique of ureteroneocystostomy (extravesical seromuscular tunnel): a
      clinical report of the first 12 cases.

PMID- 10939875
TI  - Infectious web.

PMID- 10939876
TI  - Iron status of highly active adolescents: evidence of depleted iron stores in
      gymnasts.
AB  - Much attention has focused on the nutrition and hematological profile of female
      athletes, especially gymnasts. The few studies on iron status of male adolescent
      athletes found a low incidence of iron deficiency. The present studies
      investigated the iron status of male and female gymnasts (G) and compared it with
      athletes of other sports. Subjects were 68 elite athletes (43 M, 25F) ages 12-18,
      of four sports: gymnasts (11M,12F), swimmers (11M,6F), tennis players (10M,4F),
      and table tennis players (11M,3F). All lived in the national center for gifted
      athletes, trained over 25 hr a week, ate in the same dining room, and shared a
      similar life style. Mean levels of hemoglobin (Hb), red blood cell indexes, serum
      ferritin, serum iron, and transferrin were measured in venous blood. There was no
      difference in mean Rb among gymnasts (G) and nongymnasts (NG). However Hb was
      less than 14g/dL in 45% of MG vs. only 25% in NG, and less than 13g/dL in 25% of
      premenarcheal FG vs. 15% in NG. Low transferrin saturation (<20%) was detected in
      18% of MG and 25% of FG vs. 6% and 8% in male and female NG, respectively
      (p<.05). The percentage of males suffering from low ferritin level (<20 ng/ml)
      was twice as high in G (36%) vs. NG(19%), and about 30% in all females. In
      summary, iron stores were consistently lower in MG vs. NG. Adolescent athletes of
      both genders, G in particular, are prone to nonanemic iron deficiency, which
      might compromise their health and athletic performance.

PMID- 10939877
TI  - Effect of acute resistance exercise on postexercise oxygen consumption and
      resting metabolic rate in young women.
AB  - This study determined the effect of an intense bout of resistive exercise on
      postexercise oxygen consumption, resting metabolic rate, and resting fat
      oxidation in young women (N=7, ages 22-35). On the morning of Day 1, resting
      metabolic rate (RMR) was measured by indirect calorimetry. At 13:00 hr,
      preexercise resting oxygen consumption was measured followed by 100 min of
      resistive exercise. Postexercise oxygen consumption was then measured for a 3-hr
      recovery period. On the following morning (Day 2), RMR was once again measured in
      a fasted state at 07:00. Postexercise oxygen consumption remained elevated during
      the entire 3-hr postexercise recovery period compared to the pre-exercise
      baseline. Resting metabolic rate was increased by 4.2% (p<.05) from Day 1
      (morning prior to exercise: 1,419 +/- 58 kcal/24hr) compared to Day 2 (16 hr
      following exercise: 1,479 +/- kcal/24hr). Resting fat oxidation as determined by
      the respiratory exchange ratio was also significantly elevated on Day 2 compared
      to Day 1. These results indicate that among young women, acute strenuous
      resistance exercise of the nature used in this study is capable of producing
      modest but prolonged elevations of postexercise metabolic rate and possibly fat
      oxidation.

PMID- 10939879
TI  - Announcing the winner of the IJGO prize paper award for 1999.

PMID- 10939880
TI  - ACOG educational bulletin. Primary and preventive health care for female
      adolescents. Number 254, November 1999. American College of Obstetricians and
      Gynecologists.
AB  - Although most adolescents enjoy good health, many of their behaviors put them at
      risk for negative health outcomes. Consequently, a fundamental change in the
      provision of health care services is required. Increasingly, services must be
      directed at primary and secondary prevention. As such, physicians should respond
      by making preventive services a greater component of their clinical practice. The
      approach outlined previously can help in this transition and can ensure that
      adolescents receive the services their health status demands.

PMID- 10939878
TI  - Comparison of dietary intake and eating behavior of professional road cyclists
      during training and competition.
AB  - The dietary intake and eating behavior of a group of professional elite road
      cyclists during high intensity training and competition was compared. Their
      eating pattern consisted of several snacks throughout the race or training, a
      meal eaten no later than 1 hr postexercise, supper, and breakfast. Protein intake
      showed a significant difference between evaluation times expressed in three ways:
      per total amount intake, by kg body weight, and percentage of energy supplied.
      Due to the high energy intake of these cyclists during training and competition
      (22.9 +/- 1.5, 22.4 +/- 1.7 MJ, respectively) they presented a high consumption
      of each macronutrient both in competition and in training. The eating behavior of
      these athletes was similar during breakfast (possibility to choose from among
      approximately 25 foods) and supper (set menu), with variation in the energy
      intake and a similar relative contribution of the different macronutrients. In
      general, it is possible to consider the professional road cyclists as a
      homogeneous group with a similar nutrition intake, eating habits, and nutritional
      needs throughout the more demanding periods of the season. Furthermore,
      differences found in protein intake between periods could not be explained by
      differences in the food available in competition and training periods.

PMID- 10939881
TI  - ACOG educational bulletin. Psychosocial risk factors: perinatal screening and
      intervention. Number 255, November 1999. American College of Obstetricians and
      Gynecologists.
AB  - Addressing the broad range of psychosocial issues with which pregnant women are
      confronted is an essential step toward improving women s health and birth
      outcomes. This may be difficult to do completely in a private physician s office
      setting, therefore, an effective system of referrals is helpful. To increase the
      likelihood of successful interventions, psychosocial screening should be
      performed on a regular basis and documented in the patient s prenatal record.

PMID- 10939882
TI  - [8th Educational Seminar in Hepato-gastroenterology. Paris, France, 20-21
      November 1998. Proceedings].

PMID- 10939883
TI  - What is the T(pot) for prostate cancer? Radiobiological implications of the
      equivalent outcome with (125)I or (103)Pd.

PMID- 10939884
TI  - Regarding Vicini et al., IJROBP 1999,45:553-561.

PMID- 10939885
TI  - Comments on the use of the Lyman-Kutcher-Burman model to describe tissue response
      to nonuniform irradiation.

PMID- 10939886
TI  - Influence of dose-rate on inflammatory damage and adhesion molecule expression
      after abdominal radiation in the rat.

PMID- 10939887
TI  - Clinical dose-volume histogram and lung toxicity after irradiation for lung
      cancer.

PMID- 10939888
TI  - Role of uterine natural killer cells and interferon gamma in placental
      development.

PMID- 10939889
TI  - Subsmash in Liverpool Bay--a medical and naval disaster?

PMID- 10939890
TI  - From the Centers for Disease Control and Prevention. Probable locally acquired
      mosquito-transmitted Plasmodium vivax infection--Suffolk County, New York, 1999.

PMID- 10939892
TI  - JAMA patient page. Syphilis.

PMID- 10939891
TI  - From the Centers for Disease Control and Prevention. Illnesses associated with
      use of automatic insecticide dispenser units--selected states and United States,
      1986-1999.

PMID- 10939893
TI  - [Painless labor].

PMID- 10939894
TI  - Long-branch attraction and the rDNA model of early eukaryotic evolution.
AB  - Phylogenetic analyses of ribosomal RNA genes have become widely accepted as a
      framework for understanding broad-scale eukaryotic evolution. Nevertheless,
      conflicts exist between the phylogenetic placement of certain taxa in rDNA trees
      and their expected position based on fossils, cytology, or protein-encoding gene
      sequences. For example, pelobiont amoebae appear to be an ancient group based on
      cytologic features, but they are not among the early eukaryotic brances in rDNA
      analyses. In this report, the derived position of pelobionts in rDNA trees is
      shown to be unreliable and likely due to long-branch attraction among more deeply
      branching sequences. All sequences that branch near the base of the tree suffer
      from relatively high apparent substitution rates and exhibit greater variation in
      ssu rDNA sequence length. Moreover, the order of the branches leading from the
      root of the eukaryotic tree to the base of the so-called "crown taxa" is
      consistent with a sequential attachment, due to "long-branch" effects, of
      sequences with increasing rates of evolution. These results suggest that the
      basal eurkaryotic topology drawn from rDNA analyses may be, in reality, an
      artifact of variation in the rate of molecular evolution among eukaryotic taxa.

PMID- 10939895
TI  - Images in clinical medicine. A life-threatening coronary-artery stenosis.

PMID- 10939896
TI  - The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery
      stenosis.

PMID- 10939897
TI  - The effect of balloon angioplasty on hypertension in atherosclerotic renal-artery
      stenosis.

PMID- 10939898
TI  - High-dose chemotherapy plus hematopoietic stem-cell rescue for metastatic breast
      cancer.

PMID- 10939899
TI  - High-dose chemotherapy plus hematopoietic stem-cell rescue for metastatic breast
      cancer.

PMID- 10939900
TI  - High-dose chemotherapy plus hematopoietic stem-cell rescue for metastatic breast
      cancer.

PMID- 10939901
TI  - Familial forms of thyroid dysgenesis among infants with congenital
      hypothyroidism.

PMID- 10939902
TI  - "We don't carry that".

PMID- 10939903
TI  - "We don't carry that".

PMID- 10939904
TI  - "We don't carry that".

PMID- 10939905
TI  - "We don't carry that".

PMID- 10939906
TI  - "We don't carry that".

PMID- 10939907
TI  - Fetal effects of metoclopramide therapy for nausea and vomiting of pregnancy.

PMID- 10939908
TI  - [Ultrastructural features of primary myopathy].

PMID- 10939910
TI  - Underreading of the Tuberculin skin test reaction.

PMID- 10939909
TI  - Varicella causes skin pits and keloids--more reasons for the varicella vaccine.

PMID- 10939911
TI  - "Damned if the parents cry, damned if they don't" by the nurses! Dilemma of a
      neonatologist.

PMID- 10939912
TI  - Diagnostic performance of amplified Mycobacterium Tuberculosis direct test in the
      cerebrospinal fluid of children with tuberculosis meningitis.

PMID- 10939913
TI  - Spin dryer injuries.

PMID- 10939914
TI  - Precocious puberty.

PMID- 10939916
TI  - Neuropeptides 2000. 10th Annual meeting of the European Neuropeptide Club.
      Innsbruck, Austria, May 10-13, 2000. Abstracts.

PMID- 10939915
TI  - Release of epigenetic gene silencing by trans-acting mutations in Arabidopsis.
AB  - Gene silencing in plants inactivates trans-genes introduced into plants and/or
      endogenous homologous genes. This stable but potentially reversible loss of gene
      activity resembles epigenetic changes that occur in normal development. The
      stability of silencing implies the involvement of trans-acting components,
      although none of them have been identified so far. Here we report the finding of
      second-site mutations interfering with maintenance of the silent state. We
      mutagenized Arabidopsis thaliana plants carrying a silent transgene encoding
      hygromycin phosphotransferase (hpt) and therefore show a heritable hygromycin
      sensitive phenotype. The M2 generation was screened for hygromycin resistance.
      Eight putative mutants (som1 to 8) were found that expressed the transgene and
      transmitted the expressed state to their progeny. All mutations were shown to
      reactivate a silent transgenic test locus in trans. The level of DNA methylation
      at the hpt locus and at centromeric repeats was found to be reduced in the som
      mutants. Complementation crosses indicated complex epigenetic interactions among
      the som mutant alleles and with the previously described ddm1 allele, which
      elicits DNA hypomethylation [Vongs, A., Kakutani, T, Martiensen, R.A. & Richards,
      E.J. (1993) Science 260, 1926-1928]. Som mutants can be classified into three
      groups: (i) allelic or interacting with ddm1 and with each other (som 1,4, and
      5), (ii) nonallelic with ddm1 and som mutants of group A (som2), and (iii)
      mutants with slow resilencing after out-crosses, which hinders their
      classification (som 3, 6, 7 and 8).

PMID- 10939917
TI  - Image interpretation session: 1998. The Radiological Society of North America
      84th scientific assembly and annual meeting.

PMID- 10939918
TI  - [Science according to Marcel Colla].

PMID- 10939919
TI  - [Science and politics in action].

PMID- 10939920
TI  - [Science, politics and ignorance].

PMID- 10939921
TI  - [The strained relations between science and politics].

PMID- 10939922
TI  - [When the truth hurts].

PMID- 10939923
TI  - [Consensus development conference for the elaboration of a clinical medical
      surveillance strategy for people exposed to asbestos. Paris, France, 15 January
      1999].

PMID- 10939924
TI  - [Motivated].

PMID- 10939925
TI  - [Patients afraid of the office].

PMID- 10939926
TI  - [EuroPerio 3].

PMID- 10939927
TI  - [Failures in prosthodontics: their diagnosis, causes and treatment. A report on
      the Annual Congress of the Societe Suisse de Prothese Dentaire (SSPD) at Bienne,
      2 and 3 September 1999].

PMID- 10939928
TI  - [Anonymous (Spain, 16th century): a predella of the Man of sorrow surrounded by
      saints].

PMID- 10939930
TI  - [Rationing in the health area?].

PMID- 10939929
TI  - [Alfred Alexander Steiger, DDS. A pioneer of dentistry].

PMID- 10939931
TI  - [Quality standards and the European TQM model in dental practice (II)].

PMID- 10939932
TI  - [A statement on the safety and efficacy of AH-26 root canal filling material].

PMID- 10939933
TI  - [The fluoride content in children's toothpastes].

PMID- 10939934
TI  - [Women and men dentists under stress].

PMID- 10939935
TI  - Screening hCHK2 for mutations.

PMID- 10939936
TI  - AIDS meeting. Companies, donors pledge to close gap in AIDS treatment.
AB  - Although basic science and clinical research typically dominate at this biennial
      event, by far the most riveting sessions at the XIII International AIDS
      Conference here revolved around the thicket of issues that prevent poor people in
      sub-Saharan Africa--where a staggering 24.5 million people are estimated to be
      infected with HIV--from receiving the 14 anti-HIV treatments now used in wealthy
      countries. Pharmaceutical companies and donors last week loosed a flood of
      promises about removing barriers. Conference attendees welcomed the offers of
      help, but many stressed that much more will be needed.

PMID- 10939937
TI  - Ecology. Food fight drives evolution.
AB  - On page 441 of this issue, evolutionary biologists showcase the purple-throated
      carib hummingbird as a rare example of food supply--in this case, flower shape-
      spurring the evolution of a sexual dimorphism, or a feature that differs between
      males and females. On St. Lucia, an island in the West Indies, female caribs
      sport bills a third longer and twice as curved as those of their male
      counterparts--one of the most extreme bill differences between the sexes in any
      hummingbird species. In the paper, the researchers link these "whoppingly
      dimorphic bills" to the specific flowers the male and female caribs frequent.

PMID- 10939938
TI  - Toxicology. Mercury report backs strict rules.
AB  - The debate, finally, seemed to be settled. After an 18-month review, a panel of
      the National Academy of Sciences last week weighed in on the health risks of
      mercury, endorsing strict safety levels proposed by the Environmental Protection
      Agency in 1995. But already some scientists are contesting the panel's
      conclusions, and federal agencies are grappling with how to reconcile competing
      regulations.

PMID- 10939939
TI  - Developmental biology. Why chicks aren't all thumbs.
AB  - A new study on page 438 offers some surprising insights on when and how digits
      assume their distinctive shapes. Scientists had thought that even before
      cartilage cells begin to develop into a finger or toe, they already know what
      shape digit to make. The new findings, however, suggest that digit identity is
      programmed much later in development, by chemical messengers from the surrounding
      tissue.

PMID- 10939940
TI  - Molecular biology. Targeting intron insertion into DNA.
AB  - In work reported on page 452, researchers have found a way to coax certain
      introns, bits of genetic debris that litter the DNA and interrupt the coding
      sequences of many genes, to hop into the exact sequences where the researchers
      want them. The method could enhance all sorts of genetic manipulations, from
      studying basic gene function to combating viral infections to delivering genes
      for gene therapy.

PMID- 10939941
TI  - Alzheimer's congress. Further progress on a beta-amyloid vaccine.

PMID- 10939942
TI  - Alzheimer's congress. Drug shows promise for advanced disease.

PMID- 10939943
TI  - Animal research. Activists win big on rodent, bird rules.
AB  - A federal judge last month ruled that animal-rights activists have the legal
      right to challenge U.S. Department of Agriculture rules that exempt the vast
      majority of research animals from federal regulation. Observers say that the
      ruling almost guarantees that the agency will extend regulations governing animal
      handling and housing to thousands of academic and industry laboratories that work
      with rodents and birds. Those new rules, say animal-care experts, could impose
      costly new requirements on labs that don't meet standards set by the private
      Association for Assessment and Accreditation of Laboratory Animal Care.

PMID- 10939944
TI  - Bioterrorism. DOD retreats on plan for anthrax vaccine.
AB  - Anthrax bacterium, once the deadly scourge of goat-hair workers, has become the
      bane of the U.S. defense establishment. Without infecting a single soldier, it
      has created a logistical headache for the Pentagon, as military contractors have
      fallen far short of supplying a vaccine that will protect all troops and be
      acceptable to health authorities. Last week military officials were forced to
      beat a hasty retreat in their current efforts, raising the hackles of legislators
      who already had serious doubts about the program.

PMID- 10939945
TI  - Conservation biology. When protecting one species hurts another.
AB  - Biologists studying whether providing habitat for one wide-ranging species would
      protect another--the so-called umbrella effect--have found limited overlap
      between prime grizzly habitat and that of threatened fish, and grizzly
      conservation programs here may even be hurting the fish. Researchers are now
      grappling with how best to conserve habitat for multiple species.

PMID- 10939946
TI  - Confounding factors in coral reef recovery.

PMID- 10939947
TI  - Pseudomonas survival strategies in cystic fibrosis.

PMID- 10939948
TI  - Scientists have not been silent.

PMID- 10939949
TI  - Ecology. The value of nature and the nature of value.
AB  - Ecosystems are capital assets: When properly managed, they yield a flow of vital
      goods and services. Relative to other forms of capital, however, ecosystems are
      poorly understood, scarcely monitored, and--in many important cases--undergoing
      rapid degradation. The process of economic valuation could greatly improve
      stewardship. This potential is now being realized with innovative financial
      instruments and institutional arrangements.

PMID- 10939950
TI  - Cognition. The holey grail of general intelligence.
AB  - Exactly what is human intelligence and how should we measure it? Such questions
      have plagued us since the time of Plato, who first proposed that the seat of
      intelligence is in the brain. In a Perspective, Sternberg discusses new findings
      (Duncan et al.) that purport to show that the seat of general intelligence is
      located in the brain's frontal lobes. But, as Sternberg points out, measures of
      intelligence are only as good as the tests you use and the conclusions that you
      draw from them.

PMID- 10939951
TI  - RNA structure. Ribozyme evolution at the crossroads.
AB  - Molecules that have similar sequences usually adopt the same structures and have
      the same functions. In his Perspective, Joyce explains that this is not always
      the case. In a remarkable study (Schultes and Bartel), an RNA sequence has been
      designed that can adopt two different structures, each with a different catalytic
      function. Joyce details how this study sheds light on the evolution of enzymes.

PMID- 10939952
TI  - Cell biology. ER-to-Golgi traffic--this bud's for you.
AB  - How do protein-transporting vesicles, which bud from the endoplasmic reticulum
      (ER), specifically dock to, and fuse with, the Golgi apparatus? In their
      Perspective, Brittle and Waters discuss new work (Allan et al.) suggesting that
      some vesicle-associated docking and fusion proteins are "programmed" during
      vesicle budding from the ER and direct downstream events that occur during fusion
      of these transport vesicles with the membranes of the Golgi.

PMID- 10939953
TI  - TechSight. Imaging. A molecular map for neurodegeneration.

PMID- 10939954
TI  - Emerging diseases. Malaysian researchers trace Nipah virus outbreak to bats.
AB  - Scientists are a step closer to unraveling a medical mystery that killed 105
      people in Malaysia last year and destroyed the country's pig industry. The Nipah
      virus, which caused the disease, most likely originated in a native fruit bat
      species, Malaysian researchers reported here at a meeting last week. They say the
      findings will help Malaysian health authorities prevent future outbreaks of the
      Nipah virus. Others see the case as an argument for expanding research into
      infections that can leap the boundary between animals and humans.

PMID- 10939956
TI  - Developmental biology. Embryonic lens prompts eye development.

PMID- 10939955
TI  - Neuroscience. Early insult rewires pain circuits.
AB  - On page 628, neuroscientists report that painful stimuli delivered to rats
      shortly after birth permanently rewire the spinal cord circuits that respond to
      pain. Not only do the circuits contain more axons, but the axons extend to more
      areas of the spinal cord than they normally would. The results should help
      convince skeptics of the importance of managing pain in human infants.

PMID- 10939958
TI  - Genomics. Wellcome Trust backs genome computation.

PMID- 10939957
TI  - Biomedical research. Hughes grants target infectious diseases.
AB  - The Howard Hughes Medical Institute has launched a new program of 5-year grants
      that funds 45 scientists in 20 countries. The $15 million initiative, which
      supports research on a variety of infectious and parasitic diseases, marks the
      first Hughes program outside the United States that is tailored to a specific
      research area.

PMID- 10939959
TI  - Evolution. Parasites make scaredy-rats foolhardy.

PMID- 10939961
TI  - Diabetes research. Islet transplants not yet ready for prime time.
AB  - When researchers in Edmonton, Canada, announced last month that a new procedure
      for transplanting pancreatic islet cells had freed seven adults with type I
      diabetes from taking insulin, the results generated a great deal of public
      enthusiasm. Some important caveats tended to get lost, however. One drawback is
      that transplant recipients would need to take immunosuppressive drugs for the
      rest of their lives to keep from rejecting the tissue. But more importantly, even
      if the benefits of the transplants outweigh the risks of the drugs, there's just
      not enough islet tissue to go around and there won't be anytime soon.

PMID- 10939960
TI  - 5TH International Ancient DNA Conference. Divining diet and disease from DNA.
AB  - Some 110 scientists from a range of disciplines gathered in the overcast British
      midlands for the 5th International Ancient DNA Conference, held here from 12 to
      14 July. Among the attractions were new insights into the diets of early
      Americans gleaned from ancient human coprolites and intriguing reports of nuclear
      DNA and ancient viral sequences extracted from mammoth bones.

PMID- 10939962
TI  - Toxicogenomics. Toxicologists brace for genomics revolution.
AB  - According to researchers who gathered here at a high-powered summit this month,
      toxicology may be on the verge of changing the way it collects raw data--adopting
      a process that could reduce animal use and improve test results. The new
      approach, called "toxicogenomics," uses DNA arrays to profile gene expression in
      cells exposed to test compounds. But some leaders in the field warn against
      rushing too quickly to embrace DNA tests, which are still difficult to interpret.

PMID- 10939963
TI  - Violence: a new frontier for scientific research.

PMID- 10939964
TI  - Inequities in liver transplant allocation.

PMID- 10939965
TI  - Cell biology. Sowing the protein seeds of prion propagation.
AB  - Ever since Prusiner first proposed his radical "protein-only" hypothesis to
      explain how certain infectious proteins (prions) are transmitted from one mammal
      to another in the absence of DNA or RNA, scientists have been trying to prove him
      right (or wrong). The study of mammalian prions, such as those causing
      Creutzfeldt-Jakob disease in humans, scrapie in sheep and mad cow disease in
      cattle, has been slow to yield answers. However, as Tuite discusses in his
      Perspective, the Sup35p and Ure2p proteins of yeast that exist in both normal and
      infectious forms are providing evidence that the "protein-only" hypothesis may be
      right (Sparrer et al.).

PMID- 10939966
TI  - Cell biology. A universal bicarbonate sensor.
AB  - The life-span of sperm may be short but it is certainly busy. The three principal
      molecular events that prepare sperm for fertilization are all controlled by the
      intracellular nucleotide adenosine 3',5'-monophosphate (cAMP). One of these,
      capacitation, is also regulated by bicarbonate ions. The elusive connection
      between cAMP and bicarbonate ions now appears to be solved as Kaupp and Weyand
      explain in their Perspective. Bicarbonate ions enter sperm through the anion
      transporter in the sperm plasma membrane and activate the soluble form of
      adenylyl cyclase, the enzyme that synthesizes cAMP (Chen et al.)

PMID- 10939967
TI  - Biochemistry. All in the ubiquitin family.
AB  - The job of a protein can be altered by addition of molecules such as ubiquitin or
      the related ubiquitin-like modifiers, which bring about changes in the protein's
      localization, conformation, or its interactions with other proteins. In a
      comprehensive Perspective, Hochstrasser brings us up to date with the many new
      members of the ubiquitin modifier family and their multitudinous and diverse
      protein targets.

PMID- 10939968
TI  - The shots heard 'round the world.
AB  - The massacre at Columbine High School last year unleashed a torrent of fresh
      concern over the threat that violence poses to society. It also energized a
      government research effort to understand and prevent violence. Ironically, this
      flurry of activity comes at a time when youth violence, as reflected in crime
      statistics, is in decline.

PMID- 10939969
TI  - In Europe, hooligans are prime subjects for research.
AB  - CAMBRIDGE, U.K.--One of the few burgeoning areas of violence research here and in
      Europe is football hooliganism. With lower homicide rates than in the United
      States and fewer incidences of killing sprees such as the Littleton school
      shooting, Europeans are less concerned about violence than Americans are--and
      that translates into less money for research on the topic. Moreover, some
      scientists argue that strict regulation of animal studies has dealt a severe blow
      to a once-proud European tradition of behavioral research on animal aggression.

PMID- 10939970
TI  - Searching for the mark of Cain.
AB  - MEDFORD, MASSACHUSETTS--Hampered by political, ethical, and methodological
      problems, a small group of researchers is trying to understand the biological
      roots of violence. The field has generated some interesting findings and
      hypotheses about how hormones, genes, and the brain control aggressive behavior.
      But although the goal is to ultimately find a treatment for violent behavior,
      researchers emphasize that they are not advocating drugging everybody who has
      ever committed a crime--or is deemed prone to do so.

PMID- 10939971
TI  - The snarls and sneers that keep violence at bay.
AB  - The ability to mete out violence appears to be linked to survival in the animal
      kingdom. But a handful of researchers is now making a persuasive case that scores
      are settled far more often by subtle, nonviolent signals such as a curled lip or
      a snarl. Their provocative idea is that inflicting violence on a member of one's
      own species is a pathological condition that arises when these signals are missed
      or misinterpreted.

PMID- 10939972
TI  - The violence of the lambs.
AB  - Researchers are increasingly coming to view violence as the end result of
      multiple risk factors that may include a biological vulnerability that can be
      brought out or reinforced by social environment. Longitudinal studies are
      demonstrating that children who become chronically violent adults generally are
      difficult from early childhood. But just which early risk factors are most
      powerful, and how they interact, is proving very tough to sort out.

PMID- 10939973
TI  - Has America's tide of violence receded for good?
AB  - Experts in the young field of violence epidemiology blame guns and crack cocaine
      for America's deadly crime surge in the early 1990s. Explaining the subsequent
      decline in violent crime rates has been more difficult, however. Some of the
      factors that seem to have helped squelch crime could be temporary, such as low
      unemployment rates. But others, including a growing intolerance for violence as a
      means of settling interpersonal disputes, seem to have become cultural norms.

PMID- 10939974
TI  - What makes a police officer a victim?
AB  - In the United States, about 150 police officers die every year in the line of
      duty, and government figures suggest that some 350 suspected criminals are
      justifiably killed in confrontations with police. Seeking lessons behind these
      gruesome statistics and other disturbing trends in violent behavior nationwide
      (see main text) are researchers at the Federal Bureau of Investigation.

PMID- 10939975
TI  - Predictive methods for food allergenicity: perspectives and current status.

PMID- 10939976
TI  - Edwin Beer--a patriarch of pediatric urology.

PMID- 10939977
TI  - Vascular endothelial growth factor in prostate cancer.

PMID- 10939978
TI  - "Disparaged" nephroptosis.

PMID- 10939979
TI  - Use of interoperative documentation.

PMID- 10939980
TI  - [Dissertations defended in 1999].

PMID- 10939981
TI  - [Dissertations defended in 2000].

PMID- 10939982
TI  - S1 in Wolff-Parkinson-White syndrome.

PMID- 10939983
TI  - Hyperhomocysteinemia is not a cause of calcific aortic valves.

PMID- 10939984
TI  - Jet ventilation through jet stylets.

PMID- 10939985
TI  - New medications for drug abuse. Proceedings of the Archer Conference on Drug
      Abuse: New Medications. Rensselaerville, New York, September 29-October 1, 1999.

PMID- 10939986
TI  - [Skin leiomyosarcomas and Epstein-Barr virus].

PMID- 10939987
TI  - [Leiomyosarcoma: unusual presentation].

PMID- 10939988
TI  - [Diagnosis of a case. Incipient Dupuytren's disease].

PMID- 10939989
TI  - [Diagnosis of a case. Darier's disease].

PMID- 10939990
TI  - [How can we prevent tinea capitis in schools?].

PMID- 10939991
TI  - Combined chemotherapy with or without interferon alpha N1 (IFN) for advanced
      malignant melanoma--a randomized pilot phase III study.

PMID- 10939992
TI  - The overarching challenge.

PMID- 10939993
TI  - Translating practice guidelines into patient care : guidelines at the bedside.
AB  - Practice guidelines have been developed by a myriad of government, subspecialty,
      and local organizations in an attempt to reduce undesirable variations in care
      and to improve the quality of care. Despite the current enthusiasm driving the
      creation of thousands and thousands of guidelines, their longevity will depend on
      the ability to demonstrate measurable improvements in patient care caused by the
      dissemination and implementation of guidelines. In order for guidelines to
      improve care, they must influence the decisions that physicians and other health
      care providers make as they care for patients on a day-to-day basis. Studies on
      this topic show that some guideline implementation strategies are consistently
      effective, meaning that they lead to changes in care that benefit patients. Other
      strategies have been shown to be consistently ineffective. Using an evidence
      based approach to selecting guideline dissemination and implementation strategies
      may facilitate the greatest chance of success, and enhance the probability that
      patient care will be meaningfully improved as a result of these efforts.

PMID- 10939994
TI  - Evidence for the effectiveness of techniques To change physician behavior.
AB  - STUDY OBJECTIVES: To understand the theory and results of how to improve
      physician performance, as part of overall health-care quality improvement. In
      particular, to study whether and how guideline production and dissemination
      affects physician performance. DESIGN: Review of meta-analyses and structured
      reviews; review of behavior change theories implicit in interventions to change
      physician performance. SETTING: Primarily the United States. PATIENTS OR
      PARTICIPANTS: Various patients and physicians, determined by reviews.
      INTERVENTIONS: None. MEASUREMENTS AND RESULTS: There is no unifying theory of
      physician behavior change tested among physicians in practice. Attempts to affect
      individual physicians' performance have often met with failure. Mixed results are
      found for almost all interventions reviewed. Multiple interventions yield better
      results. CONCLUSIONS: The answer to the question of what works to improve an
      individual physician's clinical performance is not simple. Emerging theory and
      evidence suggests that applications of behavior-change methods should not be
      focused on which tools (don't) always work. Instead, guideline development and
      implementation methods should be theory driven and evidence based (supported by
      evidence that proves the theory correct). In particular, the framework of
      evidence-based quality assessment offers some insight into past failures and
      offers hope for organizing attempts at guideline implementation.

PMID- 10939995
TI  - Physicians' learning strategies.
AB  - This article examines the two categories of learning strategies that physicians
      use in clinical practice. The strategies are similar in their overall
      architectures and differ (1) according to nature of the clinical problem that
      precipitated the need to learn, and (2) the ways in which learning resources are
      used.

PMID- 10939996
TI  - The role of clinical opinion leaders in guideline implementation and quality
      improvement.
AB  - BACKGROUND: The lag between the publication of clinical and health-services
      research and the application of this information is substantial and delays health
      care improvement. A wide range of corrective strategies are being used to address
      this issue. OBJECTIVES: Evolution in the use of significant opinion leaders is
      described. Hospital quality improvement projects, undertaken by the Healthcare
      Education and Research Foundation (HERF), are used to illustrate the roles
      assumed by clinical opinion leaders. Specific theoretical frameworks are reviewed
      that are fundamental to successful implementation of opinion leader strategies,
      as well as key research on the use of clinical opinion leaders. RESULTS: Over the
      past 12 years, HERF has identified the need to address not only the information
      needs of clinicians and organizations but also the social and organizational
      factors that interfere with the application of research and guidelines. The
      complexity of this task cannot be underestimated. However, armed with well
      developed guidelines and the opportunity to work within structured guideline
      implementation programs with well-defined objectives and systematically applied
      methods, HERF's experience suggest local clinicians and communities can meet this
      challenge.

PMID- 10939997
TI  - Provider education to promote implementation of clinical practice guidelines.
AB  - STUDY OBJECTIVES: Although the interest in and promulgation of clinical practice
      guidelines have significantly increased in the past 2 decades, concern exists
      about their actual implementation. This article focuses on one strategy to
      encourage guideline implementation at the clinician level: clinician education.
      The objectives of the article are to review educational strategies, to consider
      them within the context of complementary strategies carried out at the
      organizational and clinic setting levels, and to outline challenges and
      recommendations for clinicians' continuing education. METHODS: Experience and
      data from relevant randomized clinical trials within an educational framework are
      reviewed. OBSERVATIONS: Implementation of clinical practice guidelines requires a
      variety of skills, including assessment, appropriate delineation of a treatment
      and monitoring plan, patient tracking, and patient counseling and education
      skills. Continuing education strategies must reflect the content and teaching
      methods that best match the learning objectives. The pressures of current-day
      practices place limits on the resources, particularly clinician time, that are
      available for continuing education. Organizational resources must be committed to
      build the complementary supportive systems necessary for improved clinician
      practice. In addition to physicians, education must be directed at nonphysician
      clinicians, office staff, and administrators who also are responsible for
      guideline implementation. CONCLUSIONS: To meet the challenges of developing
      clinician motivation, balancing competing demands, and treating patients with
      complex medical conditions, all within time constraints, clinical leaders need to
      design education activities that have leadership support, reflect compelling
      evidence, use multiple strategies and teaching techniques, and engage learners in
      skill building and problem solving.

PMID- 10939998
TI  - Organizational interventions to encourage guideline implementation.
AB  - Evidence-based guidelines hold considerable promise for continued improvement of
      health-care delivery. However, the availability of clinical practice guidelines
      does not automatically lead to changes in practice patterns. Using a "push-pull
      capacity" model, this article describes strategies to improve guideline
      implementation for three types of organizations: national organizations, insurer
      and health-care organizations, and health-care purchasers. Push strategies focus
      on the guideline development process and include rigorous review and meta
      analysis of peer-reviewed research, and use of multidisciplinary expert teams,
      subjecting guidelines to peer review and comment and using measurable clinical
      outcomes to define guidelines. PULL: strategies focus on creating a demand for
      guideline implementation and include professional organization endorsement,
      quality measures based on guideline-related outcomes, and guideline-based
      performance objectives in purchaser contracts and physician compensation
      agreements. Capacity strategies focus on systems that facilitate guideline
      implementation. Example strategies are providing benefit coverage and
      reimbursement for guideline-based treatment protocols, and implementing clinical
      information systems for population-based tracking, outcomes monitoring, and
      benchmarking feedback.

PMID- 10939999
TI  - Computer decision support systems.
AB  - Computer decision support systems are computer applications designed to aid
      clinicians in making diagnostic and therapeutic decisions in patient care. They
      can simplify access to data needed to make decisions, provide reminders and
      prompts at the time of a patient encounter, assist in establishing a diagnosis
      and in entering appropriate orders, and alert clinicians when new patterns in
      patient data are recognized. Decision support systems that present patient
      specific recommendations in a form that can save clinicians time have been shown
      to be highly effective, sustainable tools for changing clinician behavior.
      Designing and implementing such systems is challenging because of the computing
      infrastructure required, the need for patient data in a machine-processible form,
      and the changes to existing workflow that may result. Despite these difficulties,
      there is substantial evidence from trials in a wide range of clinical settings
      that computer decision support systems help clinicians do a better job caring for
      patients. As computer-based records and order-entry systems become more common,
      automated decision support systems will be used more broadly.

PMID- 10940000
TI  - Performance measurement through audit, feedback, and profiling as tools for
      improving clinical care.
AB  - Clinical audits and practice profiling have become popular tools in the attempt
      to change physician behavior to improve quality of care. Unfortunately, the
      growing need for information on quality of care has often outpaced the
      development of standard, valid, and reliable approaches to using these tools. The
      studies of performance measurement published in the literature to date
      demonstrate varying impact on ability to improve clinical care; few are
      randomized controlled trials. While performance measurement has become a common
      practice, the science surrounding this field is still in its early stages of
      development; while it seems promising, it should be viewed as largely
      experimental.

PMID- 10940001
TI  - Implementation and physician behavior change : an industry perspective.
AB  - Clinical practice guidelines are omnipresent and increasing in number; however,
      their utility and applicability are questioned. A great deal of effort is
      expended in their creation, but how they reach their ultimate customers is very
      variable. The pharmaceutical industry has considerable resources that may assist
      in this process; however, they need to be more involved in the development of
      clinical practice guidelines. This can happen only if both guideline developers
      and industry set aside their fears, concerns, and prejudices and collectively try
      to improve health care through more appropriate management of patients.

PMID- 10940002
TI  - Clinical practice guidelines vs actual clinical practice : the asthma paradigm.
AB  - In recent years, a multitude of practice guidelines, statements, position papers,
      and "best practices" have been promulgated for a number of disease entities by a
      variety of medical societies and managed care organizations. In the case of
      asthma, for example, the National Heart, Lung, and Blood Institute of the
      National Institutes of Health (NIH) initially published guidelines for the
      diagnosis and management of asthma in 1991; these recommendations were updated in
      1997. However, health-care providers have not widely and consistently adhered to
      these guidelines. Several recent publications suggest that this underutilization
      of the NIH asthma guidelines may in part be related to a lack of understanding.
      This lack of understanding appears to span the spectrum of physicians in private
      practice, physicians working in health maintenance organizations, as well as
      university-affiliated physicians. Moreover, both primary-care physicians and
      "asthma specialists" share deficits in their knowledge base. To compound the
      problem, patients with asthma also demonstrate poor adherence to the guidelines.
      This poor adherence is evident irrespective of the patient's socioeconomic
      status. These types of data clearly indicate a need for further educational
      programs directed to both physicians and patients. However, as with the
      development and promulgation of any practice guideline, physicians need to be
      convinced that there exists compelling evidence from well-controlled clinical
      trials, for example, or from evidence-based medicine, to substantiate
      implementation of these guidelines.

PMID- 10940003
TI  - Guideline implementation in the department of defense.
AB  - To improve the effectiveness of evidence-based clinical practice guidelines
      (CPGs), four other components of implementation are necessary. Together, they
      impressively optimize the process and outcomes of health care, and reduce
      undesirable variation of care. Aside from CPGs, the four components help make up
      a successful, long-term, facility-wide, comprehensive disease-management program.
      First, executive clinical and administrative leaders need to create the
      expectation and reveal hands-on commitment. Second, work-simplification tools are
      needed to accomplish the tasks more effectively and to encourage a path of least
      resistance. Third, useful, accurate metrics are needed to provide feedback for
      patients and health-care providers who need the most assistance. These metrics
      must be easily obtained, disseminated in near-real time, patient-specific,
      anonymous to others, and penalty free. Fourth, and most important, with
      nonmonetary compensation, this review addresses the question, "What's in it for
      all the passionate people who assist in the delivery of health care?"

PMID- 10940004
TI  - Translating guidelines into clinical practice : recommendations to the American
      College of Chest Physicians.

PMID- 10940005
TI  - Novel genes coding for lithotrophic sulfur oxidation of Paracoccus pantotrophus
      GB17.
AB  - The gene region coding for lithotrophic sulfur oxidation of Paracoccus
      pantotrophus GB17 is located on a 13-kb insert of plasmid pEG12. Upstream of the
      previously described six open reading frames (ORFs) soxABCDEF with a partial
      sequence of soxA and soxF (C. Wodara, F. Bardischewsky, and C. G. Friedrich, J.
      Bacteriol. 179:5014-5023, 1997), 4,350 bp were sequenced. The sequence completed
      soxA, and uncovered six new ORFs upstream of soxA, designated ORF1, ORF2, and
      ORF3, and soxXYZ. ORF1 could encode a 275-amino-acid polypeptide of 29,332 Da
      with a 61 to 63% similarity to LysR transcriptional regulators. ORF2 could encode
      a 245-amino-acid polypeptide of 26,022 Da with the potential to form six
      transmembrane helices and with a 48 to 51% similarity to proteins involved in
      redox transport in cytochrome c biogenesis. ORF3 could encode a periplasmic
      polypeptide of 186 amino acids of 20,638 Da with a similarity to thioredoxin-like
      proteins and with a putative signal peptide of 21 amino acids. Purified SoxXA,
      SoxYZ, and SoxB are essential for thiosulfate or sulfite-dependent cytochrome c
      reduction in vitro. N-terminal and internal amino acid sequences identified SoxX,
      SoxY, SoxZ, and SoxA to be coded by the respective genes. The molecular masses of
      the mature proteins determined by electrospray ionization spectroscopy (SoxX,
      14,834 Da; SoxY, 11,094 Da; SoxZ, 11,717 Da; and SoxA, 30,452 Da) were identical
      or close to those deduced from the nucleotide sequence with differences for the
      covalent heme moieties. SoxXA represents a novel type of periplasmic c-type
      cytochromes, with SoxX as a monoheme and SoxA as a hybrid diheme cytochrome c.
      SoxYZ is an as-yet-unprecedented soluble protein. SoxY has a putative signal
      peptide with a twin arginine motif and possibly cotransports SoxZ to the
      periplasm. SoxYZ neither contains a metal nor a complex redox center, as proposed
      for proteins likely to be transported via the Tat system.

PMID- 10940007
TI  - Microarray-based identification of a novel Streptococcus pneumoniae regulon
      controlled by an autoinduced peptide.
AB  - We have identified in the Streptococcus pneumoniae genome sequence a two
      component system (TCS13, Blp [bacteriocin-like peptide]) which is closely related
      to quorum-sensing systems regulating cell density-dependent phenotypes such as
      the development of genetic competence or the production of antimicrobial peptides
      in lactic acid bacteria. In this study we present evidence that TCS13 is a
      peptide-sensing system that controls a regulon including genes encoding Blps.
      Downstream of the Blp TCS (BlpH R) we identified open reading frames (blpAB) that
      have the potential to encode an ABC transporter that is homologous to the ComA/B
      export system for the competence-stimulating peptide ComC. The putative
      translation product of blpC, a small gene located downstream of blpAB, has a
      leader peptide with a Gly-Gly motif. This leader peptide is typical of precursors
      processed by this family of transporters. Microarray-based expression profiling
      showed that a synthetic oligopeptide corresponding to the processed form of BlpC
      (BlpC*) induces a distinct set of 16 genes. The changes in the expression profile
      elicited by synthetic BlpC* depend on BlpH since insertional inactivation of its
      corresponding gene abolishes differential gene induction. Comparison of the
      promoter regions of the blp genes disclosed a conserved sequence element formed
      by two imperfect direct repeats upstream of extended -10 promoter elements. We
      propose that BlpH is the sensor for BlpC* and the conserved sequence element is a
      recognition sequence for the BlpR response regulator.

PMID- 10940006
TI  - Two novel genes induced by hard-surface contact of Colletotrichum gloeosporioides
      conidia.
AB  - Germinating conidia of many phytopathogenic fungi must differentiate into an
      infection structure called the appressorium in order to penetrate into their
      hosts. This differentiation is known to require contact with a hard surface.
      However, the molecular basis for this requirement is not known. Induction of this
      differentiation in the avocado pathogen, Colletotrichum gloeosporioides, by
      chemical signals such as the host's surface wax or the fruit-ripening hormone,
      ethylene, requires contact of the conidia with a hard surface for about 2 h. To
      study molecular events triggered by hard-surface contact, we isolated several
      genes expressed during the early stage of hard-surface treatment by a
      differential-display method. The genes that encode Colletotrichum hard-surface
      induced proteins are designated chip genes. In this study, we report the
      characterization of CHIP2 and CHIP3 genes that would encode proteins with
      molecular masses of 65 and 64 kDa, respectively, that have no homology to any
      known proteins. The CHIP2 product would contain a putative nuclear localization
      signal, a leucine zipper motif, and a heptad repeat region which might dimerize
      into coiled-coil structure. The CHIP3 product would be a nine-transmembrane
      domain-containing protein. RNA blots showed that CHIP2 and CHIP3 are induced by a
      2-h hard-surface contact. However, disruption of these genes did not affect the
      appressorium-forming ability and did not cause a significant decrease in
      virulence on avocado or tomato fruits suggesting that C. gloeosporioides might
      have genes functionally redundant to CHIP2 and CHIP3 or that these genes induced
      by hard-surface contact control processes not directly involved in pathogenesis.

PMID- 10940009
TI  - In vivo and in vitro effects of (p)ppGpp on the sigma(54) promoter Pu of the TOL
      plasmid of Pseudomonas putida.
AB  - The connection between the physiological control of the sigma(54)-dependent Pu
      promoter of the TOL plasmid pWW0 of Pseudomonas putida and the stringent response
      mediated by the alarmone (p)ppGpp has been examined in vivo an in vitro. To this
      end, the key regulatory elements of the system were faithfully reproduced in an
      Escherichia coli strain and assayed as lacZ fusions in various genetic
      backgrounds lacking (p)ppGpp or overexpressing relA. Neither the responsiveness
      of Pu to 3-methyl benzylalcohol mediated by its cognate activator XylR nor the
      down-regulation of the promoter by rapid growth were affected in relA/spoT
      strains to an extent which could account for the known physiological control that
      governs this promoter. Overexpression of the relA gene [predicted to increase
      intracellullar (p)ppGpp levels] did, however, cause a significant gain in Pu
      activity. Since such a gain might be the result of indirect effects, we resorted
      to an in vitro transcription system to assay directly the effect of ppGpp on the
      transcriptional machinery. Although we did observe a significant increase in Pu
      performance through a range of sigma(54)-RNAP concentrations, such an increase
      never exceeded twofold. The difference between these results and the behavior of
      the related Po promoter of the phenol degradation plasmid pVI150 could be traced
      to the different promoter sequences, which may dictate the type of metabolic
      signals recruited for the physiological control of sigma(54)-systems.

PMID- 10940010
TI  - RNase III processing of intervening sequences found in helix 9 of 23S rRNA in the
      alpha subclass of Proteobacteria.
AB  - We provide experimental evidence for RNase III-dependent processing in helix 9 of
      the 23S rRNA as a general feature of many species in the alpha subclass of
      Proteobacteria (alpha-Proteobacteria). We investigated 12 Rhodobacter, Rhizobium,
      Sinorhizobium, Rhodopseudomonas, and Bartonella strains. The processed region is
      characterized by the presence of intervening sequences (IVSs). The 23S rDNA
      sequences between positions 109 and 205 (Escherichia coli numbering) were
      determined, and potential secondary structures are proposed. Comparison of the
      IVSs indicates very different evolutionary rates in some phylogenetic branches,
      lateral genetic transfer, and evolution by insertion and/or deletion. We show
      that the IVS processing in Rhodobacter capsulatus in vivo is RNase III-dependent
      and that RNase III cleaves additional sites in vitro. While all IVS-containing
      transcripts tested are processed in vitro by RNase III from R. capsulatus, E.
      coli RNase III recognizes only some of them as substrates and in these substrates
      frequently cleaves at different scissile bonds. These results demonstrate the
      different substrate specificities of the two enzymes. Although RNase III plays an
      important role in the rRNA, mRNA, and bacteriophage RNA maturation, its substrate
      specificity is still not well understood. Comparison of the IVSs of helix 9 does
      not hint at sequence motives involved in recognition but reveals that the
      "antideterminant" model, which represents the most recent attempt to explain the
      E. coli RNase III specificity in vitro, cannot be applied to substrates derived
      from alpha-Proteobacteria.

PMID- 10940008
TI  - Metabolic pathways for cytotoxic end product formation from glutamate- and
      aspartate-containing peptides by Porphyromonas gingivalis.
AB  - Metabolic pathways involved in the formation of cytotoxic end products by
      Porphyromonas gingivalis were studied. The washed cells of P. gingivalis ATCC
      33277 utilized peptides but not single amino acids. Since glutamate and aspartate
      moieties in the peptides were consumed most intensively, a dipeptide of glutamate
      or aspartate was then tested as a metabolic substrate of P. gingivalis. P.
      gingivalis cells metabolized glutamylglutamate to butyrate, propionate, acetate,
      and ammonia, and they metabolized aspartylaspartate to butyrate, succinate,
      acetate, and ammonia. Based on the detection of metabolic enzymes in the cell
      extracts and stoichiometric calculations (carbon recovery and oxidation/reduction
      ratio) during dipeptide degradation, the following metabolic pathways were
      proposed. Incorporated glutamylglutamate and aspartylaspartate are hydrolyzed to
      glutamate and aspartate, respectively, by dipeptidase. Glutamate is deaminated
      and oxidized to succinyl-coenzyme A (CoA) by glutamate dehydrogenase and 2
      oxoglutarate oxidoreductase. Aspartate is deaminated into fumarate by aspartate
      ammonia-lyase and then reduced to succinyl-CoA by fumarate reductase and acyl
      CoA:acetate CoA-transferase or oxidized to acetyl-CoA by a sequential reaction of
      fumarase, malate dehydrogenase, oxaloacetate decarboxylase, and pyruvate
      oxidoreductase. The succinyl-CoA is reduced to butyryl-CoA by a series of
      enzymes, including succinate-semialdehyde dehydrogenase, 4-hydroxybutyrate
      dehydrogenase, and butyryl-CoA oxidoreductase. A part of succinyl-CoA could be
      converted to propionyl-CoA through the reactions initiated by methylmalonyl-CoA
      mutase. The butyryl- and propionyl-CoAs thus formed could then be converted into
      acetyl-CoA by acyl-CoA:acetate CoA-transferase with the formation of
      corresponding cytotoxic end products, butyrate and propionate. The formed acetyl
      CoA could then be metabolized further to acetate.

PMID- 10940011
TI  - The mitochondrial alcohol dehydrogenase Adh3p is involved in a redox shuttle in
      Saccharomyces cerevisiae.
AB  - NDI1 is the unique gene encoding the internal mitochondrial NADH dehydrogenase of
      Saccharomyces cerevisiae. The enzyme catalyzes the transfer of electrons from
      intramitochondrial NADH to ubiquinone. Surprisingly, NDI1 is not essential for
      respiratory growth. Here we demonstrate that this is due to in vivo activity of
      an ethanol-acetaldehyde redox shuttle, which transfers the redox equivalents from
      the mitochondria to the cytosol. Cytosolic NADH can be oxidized by the external
      NADH dehydrogenases. Deletion of ADH3, encoding mitochondrial alcohol
      dehydrogenase, did not affect respiratory growth in aerobic, glucose-limited
      chemostat cultures. Also, an ndi1Delta mutant was capable of respiratory growth
      under these conditions. However, when both ADH3 and NDI1 were deleted, metabolism
      became respirofermentative, indicating that the ethanol-acetaldehyde shuttle is
      essential for respiratory growth of the ndi1 delta mutant. In anaerobic batch
      cultures, the maximum specific growth rate of the adh3 delta mutant (0.22 h(-1))
      was substantially reduced compared to that of the wild-type strain (0.33 h(-1)).
      This is consistent with the hypothesis that the ethanol-acetaldehyde shuttle is
      also involved in maintenance of the mitochondrial redox balance under anaerobic
      conditions. Finally, it is shown that another mitochondrial alcohol dehydrogenase
      is active in the adh3 delta ndi1 delta mutant, contributing to residual redox
      shuttle activity in this strain.

PMID- 10940012
TI  - The membrane-bound H(+)-ATPase complex is essential for growth of Lactococcus
      lactis.
AB  - The eight genes which encode the (F(1)F(o)) H(+)-ATPase in Lactococcus lactis
      subsp. cremoris MG1363 were cloned and sequenced. The genes were organized in an
      operon with the gene order atpEBFHAGDC; i.e., the order of atpE and atpB is
      reversed with respect to the more typical bacterial organization. The deduced
      amino acid sequences of the corresponding H(+)-ATPase subunits showed significant
      homology with the subunits from other organisms. Results of Northern blot
      analysis showed a transcript at approximately 7 kb, which corresponds to the size
      of the atp operon. The transcription initiation site was mapped by primer
      extension and coincided with a standard promoter sequence. In order to analyze
      the importance of the H(+)-ATPase for L. lactis physiology, a mutant strain was
      constructed in which the original atp promoter on the chromosome was replaced
      with an inducible nisin promoter. When grown on GM17 plates the resulting strain
      was completely dependent on the presence of nisin for growth. These data
      demonstrate that the H(+)-ATPase is essential for growth of L. lactis under these
      conditions.

PMID- 10940013
TI  - Genetic analysis of a gene cluster for cyclohexanol oxidation in Acinetobacter
      sp. Strain SE19 by in vitro transposition.
AB  - Biological oxidation of cyclic alcohols normally results in formation of the
      corresponding dicarboxylic acids, which are further metabolized and enter the
      central carbon metabolism in the cell. We isolated an Acinetobacter sp. from an
      industrial wastewater bioreactor that utilized cyclohexanol as a sole carbon
      source. A cosmid library was constructed from Acinetobacter sp. strain SE19, and
      oxidation of cyclohexanol to adipic acid was demonstrated in recombinant
      Escherichia coli carrying a SE19 DNA segment. A region that was essential for
      cyclohexanol oxidation was localized to a 14-kb fragment on the cosmid DNA.
      Several putative open reading frames (ORFs) that were expected to encode enzymes
      catalyzing the conversion of cyclohexanol to adipic acid were identified. Whereas
      one ORF showed high homology to cyclohexanone monooxygenase from Acinetobacter
      sp. strain NCIB 9871, most of the ORFs showed only moderate homology to proteins
      in GenBank. In order to assign functions of the various ORFs, in vitro transposon
      mutagenesis was performed using the cosmid DNA as a target. A set of transposon
      mutants with a single insertion in each of the ORFs was screened for cyclohexanol
      oxidation in E. coli. Several of the transposon mutants accumulated a variety of
      cyclohexanol oxidation intermediates. The in vitro transposon mutagenesis
      technique was shown to be a powerful tool for rapidly assigning gene functions to
      all ORFs in the pathway.

PMID- 10940014
TI  - Chitin synthesis in a gas1 mutant of Saccharomyces cerevisiae.
AB  - The existence of a compensatory mechanism in response to cell wall damage has
      been proposed in yeast cells. The increase of chitin accumulation is part of this
      response. In order to study the mechanism of the stress-related chitin synthesis,
      we tested chitin synthase I (CSI), CSII, and CSIII in vitro activities in the
      cell-wall-defective mutant gas1 delta. CSI activity increased twofold with
      respect to the control, a finding in agreement with an increase in the expression
      of the CHS1 gene. However, deletion of the CHS1 gene did not affect the phenotype
      of the gas1 delta mutant and only slightly reduced the chitin content.
      Interestingly, in chs1 gas1 double mutants the lysed-bud phenotype, typical of
      chs1 null mutant, was suppressed, although in gas1 cells there was no reduction
      in chitinase activity. CHS3 expression was not affected in the gas1 mutant.
      Deletion of the CHS3 gene severely compromised the phenotype of gas1 cells,
      despite the fact that CSIII activity, assayed in membrane fractions, did not
      change. Furthermore, in chs3 gas1 cells the chitin level was about 10% that of
      gas1 cells. Thus, CSIII is the enzyme responsible for the hyperaccumulation of
      chitin in response to cell wall stress. However, the level of enzyme or the in
      vitro CSIII activity does not change. This result suggests that an interaction
      with a regulatory molecule or a posttranslational modification, which is not
      preserved during membrane fractionation, could be essential in vivo for the
      stress-induced synthesis of chitin.

PMID- 10940015
TI  - A two-dimensional protein gel electrophoresis study of the heat stress response
      of Bacillus subtilis cells during sporulation.
AB  - The heat resistance of spores of Bacillus subtilis formed at 30 degrees C was
      enhanced by pretreatment at 48 degrees C for 30 min, 60 min into sporulation, for
      all four strains examined. High-resolution two-dimensional gel electrophoresis
      showed the generation and/or overexpression of 60 proteins, 11 of which were
      specific to heat shock, concurrent to this acquired thermotolerance. The greatest
      number of new proteins was observed between 30 and 60 min after heat shock, and
      the longer the time between exponential growth and heat treatment, the fewer
      differences were observed on corresponding protein profiles. The time at which
      heating produced the maximum increase in spore resistance and the most new
      proteins on two-dimensional gels occurred before alkaline phosphatase and
      dipicolinic acid production and corresponded to stage I or II of sporulation. The
      stress proteins formed disappeared later in sporulation, suggesting that heat
      shock proteins increase spore heat resistance by altering spore structure rather
      than by repairing heat damage during germination and outgrowth.

PMID- 10940016
TI  - Mutations in each of the tol genes of Pseudomonas putida reveal that they are
      critical for maintenance of outer membrane stability.
AB  - The outer membrane of gram-negative bacteria functions as a permeability barrier
      that protects cells against a large number of antibacterial agents. OprL protein
      of Pseudomonas putida has been shown to be crucial to maintain the stability of
      this cell component (J. J. Rodriguez-Herva, M.-I. Ramos-Gonzalez, and J. L.
      Ramos. J. Bacteriol. 178:1699-1706, 1996). In the present study we cloned and
      mutagenized the orf1, tolQ, tolR, tolA, and tolB genes from P. putida KT2440,
      which were located upstream of the oprL gene. Polar and nonpolar mutations of the
      P. putida tolQ, tolR, tolA, and tolB genes were generated in vitro by using the
      omega-Km(r) interposon, which carries two transcriptional stop signals, or a
      promoterless xylE cassette, lacking any transcriptional stop signal,
      respectively. The mutant constructs were used to inactivate, by reverse genetics
      procedures, the corresponding chromosomal copies of the genes. The phenotype of
      each mutant strain was analyzed and compared with those of the wild-type strain
      and the previously characterized P. putida oprL::xylE mutant. All mutant strains
      exhibited a similar phenotype: altered cell morphology, bleb formation at the
      cell surface, release of periplasmic and outer membrane proteins to the
      extracellular medium, increased sensitivity to a variety of compounds (i.e.,
      EDTA, sodium dodecyl sulfate, deoxycholate, and some antibiotics), filament
      formation, and severely reduced cell motility. Altogether, these results
      demonstrate the importance of the Tol-OprL system for the maintenance of outer
      membrane integrity in P. putida and suggest a possible role of these proteins in
      assembling outer membrane components.

PMID- 10940017
TI  - Native corrinoids from Clostridium cochlearium are adeninylcobamides:
      spectroscopic analysis and identification of pseudovitamin B(12) and factor A.
AB  - The corrinoids from the obligate anaerobe Clostridium cochlearium were extracted
      as a mixture of Co(beta)-cyano derivatives. From 50 g of frozen cells,
      approximately 2 mg (1.5 micromol) of B(12) derivatives was obtained as a
      crystalline sample. Analysis of the corrinoid sample of C. cochlearium by a
      combination of high-pressure liquid chromatography and UV-Vis absorbance
      spectroscopy revealed the presence of three cyano corrinoids in a ratio of about
      3:1:1. The spectroscopic data acquired for the sample indicated the main
      components to be pseudovitamin B(12) (Co(beta)-cyano-7"-adeninylcobamide) (60%)
      and factor A (Co(beta)-cyano-7"-[2-methyl]adeninylcobamide) (20%). Authentic
      pseudovitamin B(12) was prepared by guided biosynthesis from cobinamide and
      adenine. Both pseudovitamin B(12) and its homologue, factor A, were subjected to
      complete spectroscopic analysis by UV-Vis, circular dichroism, mass spectrometry,
      and by one- and two-dimensional (1)H, (13)C-, and (15)N nuclear magnetic
      resonance (NMR) spectroscopy. The third component was indicated by the mass
      spectra to be an isomer of factor A and is likely (according to NMR) to be 7"
      [N(6)-methyl]-adeninylcobamide, a previously unknown corrinoid. C. cochlearium
      thus biosynthesizes as its native "complete" B(12) cofactors the 7"
      adeninylcobamides and two homologous corrinoids, in which the nucleotide base is
      a methylated adenine.

PMID- 10940018
TI  - Synthesis and posttranslational regulation of pyruvate formate-lyase in
      Lactococcus lactis.
AB  - The enzyme pyruvate formate-lyase (PFL) from Lactococcus lactis was produced in
      Escherichia coli and purified to obtain anti-PFL antibodies that were shown to be
      specific for L. lactis PFL. It was demonstrated that activated L. lactis PFL was
      sensitive to oxygen, as in E. coli, resulting in the cleavage of the PFL
      polypeptide. The PFL protein level and its in vivo activity and regulation were
      shown by Western blotting, enzyme-linked immunosorbent assay, and metabolite
      measurement to be dependent on the growth conditions. The PFL level during
      anaerobic growth on the slowly fermentable sugar galactose was higher than that
      on glucose. This shows that variation in the PFL protein level may play an
      important role in the regulation of metabolic shift from homolactic to mixed-acid
      product formation, observed during growth on glucose and galactose, respectively.
      During anaerobic growth in defined medium, complete activation of PFL was
      observed. Strikingly, although no formate was produced during aerobic growth of
      L. lactis, PFL protein was indeed detected under these conditions, in which the
      enzyme is dispensable due to the irreversible inactivation of PFL by oxygen. In
      contrast, no oxygenolytic cleavage was detected during aerobic growth in complex
      medium. This observation may be the result of either an effective PFL deactivase
      activity or the lack of PFL activation. In E. coli, the PFL deactivase activity
      resides in the multifunctional alcohol dehydrogenase ADHE. It was shown that in
      L. lactis, ADHE does not participate in the protection of PFL against oxygen
      under the conditions analyzed. Our results provide evidence for major differences
      in the mechanisms of posttranslational regulation of PFL activity in E. coli and
      L. lactis.

PMID- 10940019
TI  - Antigen 43 from Escherichia coli induces inter- and intraspecies cell aggregation
      and changes in colony morphology of Pseudomonas fluorescens.
AB  - Antigen 43 (Ag43) is a surface-displayed autotransporter protein of Escherichia
      coli. By virtue of its self-association characteristics, this protein is able to
      mediate autoaggregation and flocculation of E. coli cells in static cultures.
      Additionally, surface display of Ag43 is associated with a distinct frizzy colony
      morphology in E. coli. Here we show that Ag43 can be expressed in a functional
      form on the surface of the environmentally important Pseudomonas fluorescens
      strain SBW25 with ensuing cell aggregation and frizzy colony types. Using green
      fluorescence protein-tagged cells, we demonstrate that Ag43 can be used as a tool
      to provide interspecies cell aggregation between E. coli and P. fluorescens.
      Furthermore, Ag43 expression enhances biofilm formation in P. fluorescens to
      glass surfaces. The versatility of this protein was also reflected in Ag43
      surface display in a variety of other gram-negative bacteria. Display of
      heterologous Ag43 in selected bacteria might offer opportunities for rational
      design of multispecies consortia where the concerted action of several bacterial
      species is required, e.g., waste treatment and degradation of pollutants.

PMID- 10940020
TI  - Stationary-phase variation due to transposition of novel insertion elements in
      Xanthomonas oryzae pv. oryzae.
AB  - Xanthomonas oryzae pv. oryzae causes bacterial leaf blight, a serious disease of
      rice. Spontaneous mutants which are deficient for virulence and extracellular
      polysaccharide (Eps) production accumulate in large numbers in stationary-phase
      cultures of this bacterium, a phenomenon which we have called stationary-phase
      variation. A clone (pSD1) carrying the Eps biosynthetic gene (gum) cluster of X.
      oryzae pv. oryzae restored Eps production and virulence to several spv (for
      stationary-phase variation) mutants. Data from localized recombination analysis,
      Southern hybridization, PCR amplification, and sequence analysis showed that the
      mutations are due to insertion of either one of two novel endogenous insertion
      sequence (IS) elements, namely, ISXo1 and ISXo2, into gumM, the last gene of the
      gum gene cluster. The results of Southern analysis indicate the presence of
      multiple copies of both IS elements in the genome of X. oryzae pv. oryzae. These
      results demonstrate the role of IS elements in stationary-phase variation in X.
      oryzae pv. oryzae.

PMID- 10940021
TI  - Entry into and release of solvents by Escherichia coli in an organic-aqueous two
      liquid-phase system and substrate specificity of the AcrAB-TolC solvent-extruding
      pump.
AB  - Growth of Escherichia coli is inhibited upon exposure to a large volume of a
      harmful solvent, and there is an inverse correlation between the degree of
      inhibition and the log P(OW) of the solvent, where P(OW) is the partition
      coefficient measured for the partition equilibrium established between the n
      octanol and water phases. The AcrAB-TolC efflux pump system is involved in
      maintaining intrinsic solvent resistance. We inspected the solvent resistance of
      delta acrAB and/or delta tolC mutants in the presence of a large volume of
      solvent. Both mutants were hypersensitive to weakly harmful solvents, such as
      nonane (log P(OW) = 5.5). The delta tolC mutant was more sensitive to nonane than
      the delta acrAB mutant. The solvent entered the E. coli cells rapidly. Entry of
      solvents with a log P(OW) higher than 4.4 was retarded in the parent cells, and
      the intracellular levels of these solvents were maintained at low levels. The
      delta tolC mutant accumulated n-nonane or decane (log P(OW) = 6. 0) more
      abundantly than the parent or the delta acrAB mutant. The AcrAB-TolC complex
      likely extrudes solvents with a log P(OW) in the range of 3.4 to 6.0 through a
      first-order reaction. The most favorable substrates for the efflux system were
      considered to be octane, heptane, and n-hexane.

PMID- 10940022
TI  - Competition between the Yops of Yersinia enterocolitica for delivery into
      eukaryotic cells: role of the SycE chaperone binding domain of YopE.
AB  - A type III secretion-translocation system allows Yersinia adhering at the surface
      of animal cells to deliver a cocktail of effector Yops (YopH, -O, -P, -E, -M, and
      -T) into the cytosol of these cells. Residues or codons 1 to 77 contain all the
      information required for the complete delivery of YopE into the target cell
      (release from the bacterium and translocation across the eukaryotic cell
      membrane). Residues or codons 1 to 15 are sufficient for release from the wild
      type bacterium under Ca(2+)-chelating conditions but not for delivery into target
      cells. Residues 15 to 50 comprise the binding domain for SycE, a chaperone
      specific for YopE that is necessary for release and translocation of full-length
      YopE. To understand the role of this chaperone, we studied the delivery of YopE
      Cya reporter proteins and YopE deletants by polymutant Yersinia devoid of most of
      the Yop effectors (delta HOPEM and delta THE strains). We first tested YopE-Cya
      hybrid proteins and YopE proteins deleted of the SycE-binding site. In contrast
      to wild-type strains, these mutants delivered YopE(15)-Cya as efficiently as
      YopE(130)-Cya. They were also able to deliver YopE(delta 17-77). SycE was
      dispensable for these deliveries. These results show that residues or codons 1 to
      15 are sufficient for delivery into eukaryotic cells and that there is no
      specific translocation signal in Yops. However, the fact that the SycE-binding
      site and SycE were necessary for delivery of YopE by wild-type Yersinia suggests
      that they could introduce hierarchy among the effectors to be delivered. We then
      tested a YopE-Cya hybrid and YopE proteins deleted of amino acids 2 to 15 but
      containing the SycE-binding domain. These constructs were neither released in
      vitro upon Ca(2+) chelation nor delivered into cells by wild-type or polymutant
      bacteria, casting doubts on the hypothesis that SycE could be a secretion pilot.
      Finally, it appeared that residues 50 to 77 are inhibitory to YopE release and
      that binding of SycE overcomes this inhibitory effect. Removal of this domain
      allowed in vitro release and delivery in cells in the absence as well as in the
      presence of SycE.

PMID- 10940023
TI  - Analysis of genetic elements controlling Staphylococcus aureus lrgAB expression:
      potential role of DNA topology in SarA regulation.
AB  - Penicillin-induced killing and murein hydrolase activity in Staphylococcus aureus
      are dependent on a variety of regulatory elements, including the LytSR two
      component regulatory system and the virulence factor regulators Agr and Sar. The
      LytSR effects on these processes can be explained, in part, by the recent finding
      that a LytSR-regulated operon, designated lrgAB, affects murein hydrolase
      activity and penicillin tolerance. To examine the regulation of lrgAB expression
      in greater detail, we performed Northern blot and promoter fusion analyses. Both
      methods revealed that Agr and Sar, like LytSR, positively regulate lrgAB
      expression. A mutation in the agr locus reduced lrgAB expression approximately
      sixfold, while the sar mutation reduced lrgAB expression to undetectable levels.
      cis-acting regulatory elements involved in lrgAB expression were identified by
      fusing various fragments of the lrgAB promoter region to the xylE reporter gene
      and integrating these constructs into the chromosome. Catechol 2,3-dioxygenase
      assays identified DNA sequences, including an inverted repeat and intrinsic bend
      sites, that contribute to maximal lrgAB expression. Confirmation of the
      importance of the inverted repeat was achieved by demonstrating that multiple
      copies of the inverted repeat reduced lrgAB promoter activity, presumably by
      titrating out a positive regulatory factor. The results of this study demonstrate
      that lrgAB expression responds to a variety of positive regulatory factors and
      suggest that specific DNA topology requirements are important for optimal
      expression.

PMID- 10940025
TI  - Molecular characterization of the beta-N-acetylglucosaminidase of Escherichia
      coli and its role in cell wall recycling.
AB  - The beta-N-acetylglucosaminidase of Escherichia coli was found to have a novel
      specificity and to be encoded by a gene (nagZ) that maps at 25.1 min. It
      corresponds to an open reading frame, ycfO, whose predicted amino acid sequence
      is 57% identical to that of Vibrio furnissii ExoII. NagZ hydrolyzes the beta-1,4
      glycosidic bond between N-acetylglucosamine and anhydro-N-acetylmuramic acid in
      cell wall degradation products following their importation into the cell during
      the process for recycling cell wall muropeptides. From amino acid sequence
      comparisons, the novel beta-N-acetylglucosaminidase appears to be conserved in
      all 12 gram-negative bacteria whose complete or partial genome sequence data are
      available.

PMID- 10940024
TI  - Inactivation of the ampDE operon increases transcription of algD and affects
      morphology and encystment of Azotobacter vinelandii.
AB  - Transcription of algD, encoding GDP-mannose dehydrogenase, the key enzyme in the
      alginate biosynthetic pathway, is highly regulated in Azotobacter vinelandii. We
      describe here the characterization of a Tn5 insertion mutant (AC28) which shows a
      higher level of expression of an algD::lacZ fusion. AC28 cells were
      morphologically abnormal and unable to encyst. The cloning and nucleotide
      sequencing of the Tn5-disrupted locus in AC28 revealed an operon homologous to
      the Escherichia coli ampDE operon. Tn5 was located within the ampD gene, encoding
      a cytosolic N-acetyl-anhydromuramyl-L-alanine amidase that participates in the
      intracellular recycling of peptidoglycan fragments. The ampE gene encodes a
      transmembrane protein, but the function of the protein is not known. We
      constructed strains carrying ampD or ampE mutations and one with an ampDE
      deletion. The strain with a deletion of the ampDE operon showed a phenotype
      similar to that of mutant AC28. The present work demonstrates that both alginate
      production and bacterial encystment are greatly influenced by the bacterial
      ability to recycle its cell wall.

PMID- 10940026
TI  - Relative roles of the fla/che P(A), P(D-3), and P(sigD) promoters in regulating
      motility and sigD expression in Bacillus subtilis.
AB  - Three promoters have been identified as having potentially important regulatory
      roles in governing expression of the fla/che operon and of sigD, a gene that lies
      near the 3' end of the operon. Two of these promoters, fla/che P(A) and P(D-3),
      lie upstream of the >26-kb fla/che operon. The third promoter, P(sigD), lies
      within the operon, immediately upstream of sigD. fla/che P(A), transcribed by E
      sigma(A), lies >/=24 kb upstream of sigD and appears to be largely responsible
      for sigD expression. P(D-3), transcribed by E sigma(D), has been proposed to
      participate in an autoregulatory positive feedback loop. P(sigD), a minor
      sigma(A)-dependent promoter, has been implicated as essential for normal
      expression of the fla/che operon. We tested the proposed functions of these
      promoters in experiments that utilized strains that bear chromosomal deletions of
      fla/che P(A), P(D-3), or P(sigD). Our analysis of these strains indicates that
      fla/che P(A) is absolutely essential for motility, that P(D-3) does not function
      in positive feedback regulation of sigD expression, and that P(sigD) is not
      essential for normal fla/che expression. Further, our results suggest that an
      additional promoter(s) contributes to sigD expression.

PMID- 10940027
TI  - A homologue of an operon required for DNA transfer in Agrobacterium is required
      in Brucella abortus for virulence and intracellular multiplication.
AB  - As part of a Brucella abortus 2308 genome project carried out in our laboratory,
      we identified, cloned, and sequenced a genomic DNA fragment containing a locus
      (virB) highly homologous to bacterial type IV secretion systems. The B. abortus
      virB locus is a collinear arrangement of 13 open reading frames (ORFs). Between
      virB1 and virB2 and downstream of ORF12, two degenerated, palindromic repeat
      sequences characteristic of Brucella intergenic regions were found. Gene reporter
      studies demonstrated that the B. abortus virB locus constitutes an operon
      transcribed from virB1 which is turned on during the stationary phase of growth.
      A B. abortus polar virB1 mutant failed to replicate in HeLa cells, indicating
      that the virB operon plays a critical role in intracellular multiplication.
      Mutants with polar and nonpolar mutations introduced in virB10 showed different
      behaviors in mice and in the HeLa cell infection assay, suggesting that virB10
      per se is necessary for the correct function of this type IV secretion apparatus.
      Mouse infection assays demonstrated that the virB operon constitutes a major
      determinant of B. abortus virulence. It is suggested that putative effector
      molecules secreted by this type IV secretion system determine routing of B.
      abortus to an endoplasmic reticulum-related replication compartment.

PMID- 10940028
TI  - Effects of organic antagonists of Ca(2+), Na(+), and K(+) on chemotaxis and
      motility of escherichia coli.
AB  - Various Ca(2+) antagonists used in animal research, many of them known to be
      Ca(2+) channel blockers, inhibited Escherichia coli chemotaxis (measured as entry
      of cells into a capillary containing attractant). The most effective of these,
      acting in the nanomolar range, was omega-conotoxin GVIA. The next most effective
      were gallopamil and verapamil. At concentrations around 100-fold higher than that
      needed for inhibition of chemotaxis, each of these antagonists inhibited motility
      (measured as entry of cells into a capillary lacking attractant). Various other
      Ca(2+) antagonists were less effective, though chemotaxis was almost always more
      sensitive to inhibition than was motility. Cells treated with each of these
      Ca(2+) antagonists swam with a running bias, i.e., tumbling was inhibited.
      Similarly, some Na(+) antagonists used in animal research inhibited bacterial
      chemotaxis. E. coli chemotaxis was inhibited by saxitoxin at concentrations above
      10(-7) M, while more than 10(-4) M was needed to inhibit motility. Cells treated
      with saxitoxin swam with a tumbling bias. In the case of other Na(+) antagonists
      in animals, aconitine inhibited bacterial chemotaxis 10 times more effectively
      than it inhibited motility, and two others inhibited chemotaxis and motility at
      about the same concentration. In the case of K(+) antagonists used in animal
      research, 4-aminopyridine blocked E. coli chemotaxis between 10(-3) M and,
      totally, 10(-2) M, while motility was not affected at 10(-2) M; on the other
      hand, tetraethylammonium chloride failed to inhibit either chemotaxis or motility
      at 10(-2) M.

PMID- 10940029
TI  - Identification of the gene encoding sulfopyruvate decarboxylase, an enzyme
      involved in biosynthesis of coenzyme M.
AB  - The products of two adjacent genes in the chromosome of Methanococcus jannaschii
      are similar to the amino and carboxyl halves of phosphonopyruvate decarboxylase,
      the enzyme that catalyzes the second step of fosfomycin biosynthesis in
      Streptomyces wedmorensis. These two M. jannaschii genes were recombinantly
      expressed in Escherichia coli, and their gene products were tested for the
      ability to catalyze the decarboxylation of a series of alpha-ketoacids. Both
      subunits are required to form an alpha(6)beta(6) dodecamer that specifically
      catalyzes the decarboxylation of sulfopyruvic acid to sulfoacetaldehyde. This
      transformation is the fourth step in the biosynthesis of coenzyme M, a crucial
      cofactor in methanogenesis and aliphatic alkene metabolism. The M. jannaschii
      sulfopyruvate decarboxylase was found to be inactivated by oxygen and reactivated
      by reduction with dithionite. The two subunits, designated ComD and ComE,
      comprise the first enzyme for the biosynthesis of coenzyme M to be described.

PMID- 10940030
TI  - Spy1, a histidine-containing phosphotransfer signaling protein, regulates the
      fission yeast cell cycle through the Mcs4 response regulator.
AB  - Common histidine-to-aspartate (His-to-Asp) phosphorelay signaling systems involve
      three types of signaling components: a sensor His kinase, a response regulator,
      and a histidine-containing phosphotransfer (HPt) protein. In the fission yeast
      Schizosaccharomyces pombe, two response regulators, Mcs4 and Prr1, have been
      identified recently, and it was shown that they are involved in the signal
      transduction implicated in stress responses. Furthermore, Mcs4 appears to be
      involved in mitotic cell-cycle control. However, neither the HPt
      phosphotransmitter nor His kinase has been characterized in S. pombe. In this
      study, we identified a gene encoding an HPt phosphotransmitter, named Spy1 (S.
      pombe YPD1-like protein). The spy1(+) gene showed an ability to complement a
      mutational lesion of the Saccharomyces cerevisiae YPD1 gene, which is involved in
      an osmosensing signal transduction. The result from yeast two-hybrid analysis
      indicated that Spy1 interacts with Mcs4. To gain insight into the function of
      Spy1, a series of genetic analyses were conducted. The results provided evidence
      that Spy1, together with Mcs4, plays a role in regulation of the G(2)/M cell
      cycle progression. Spy1-deficient cells appear to be precocious in the entry to M
      phase. In the proposed model, Spy1 modulates Mcs4 in a negative manner,
      presumably through a direct His-to-Asp phosphorelay, operating upstream of the
      Sty1 mitogen-activated protein kinase cascade.

PMID- 10940031
TI  - Identification of the mob genes of plasmid pSC101 and characterization of a
      hybrid pSC101-R1162 system for conjugal mobilization.
AB  - Similarities in DNA base sequence indicate that pSC101 and R1162 encode related
      systems for conjugal mobilization, although these plasmids are otherwise very
      different. The mob region of pSC101 was cloned, and two genes that are required
      for transfer were identified. One gene, mobA, encodes a protein similar in amino
      acid sequence to the DNA processing domain of the R1162 MobA protein. The other
      gene, mobX, is within the same transcriptional unit as the pSC101 mobA and is
      located just downstream, at the same position occupied by mobB in R1162. Despite
      this, the MobB and MobX proteins do not appear to be closely related based on a
      comparison of their amino acid sequences. Complementation analysis indicated that
      neither of the pSC101 Mob proteins could substitute for, or be replaced by, their
      R1162 counterparts, nor were they active together at the R1162 origin of transfer
      (oriT). However, the full set of R1162 Mob proteins did recognize the pSC101
      oriT. A hybrid system for mobilization, active at the R1162 oriT site, was
      constructed. This system consists of MobX and a chimeric protein made up of the
      DNA cleaving-ligating domain of the R1162 MobA protein joined to a fragment of
      pSC101 MobA. Previous results suggested that MobB and a region of MobA distinct
      from the DNA processing domain together formed a functional unit in transfer. The
      present results support this model because the chimeric MobA, although active on
      R1162 oriT, requires the pSC101 protein MobX for efficient plasmid mobilization.

PMID- 10940032
TI  - Overexpression of protease-deficient DegP(S210A) rescues the lethal phenotype of
      Escherichia coli OmpF assembly mutants in a degP background.
AB  - Replacement of OmpF's conserved carboxy-terminal phenylalanine with dissimilar
      amino acids severely impaired its assembly into stable trimers. In some
      instances, interactions of mutant proteins with the outer membrane were also
      affected, as judged by their hypersensitivity phenotype. Synthesis of all mutant
      OmpF proteins elevated the expression of periplasmic protease DegP, and synthesis
      of most of them made its presence obligatory for cell viability. These results
      showed a critical role for DegP in the event of aberrant outer membrane protein
      assembly. The lethal phenotype of mutant OmpF proteins in a degP null background
      was eliminated when a protease-deficient DegP(S210A) protein was overproduced.
      Our data showed that this rescue from lethality and a subsequent increase in
      mutant protein levels in the envelope did not lead to the proper assembly of the
      mutant proteins in the outer membrane. Rather, a detergent-soluble and
      thermolabile OmpF species resembling monomers accumulated in the mutants, and to
      a lesser extent in the parental strain, when DegP(S210A) was overproduced.
      Interestingly, this also led to the localization of a significant amount of
      mutant polypeptides to the inner membrane, where DegP(S210A) also fractionated.
      These results suggested that the DegP(S210A)-mediated rescue from toxicity
      involved preferential sequestration of misfolded OmpF monomers from the normal
      assembly pathway.

PMID- 10940033
TI  - The stringent response of Mycobacterium tuberculosis is required for long-term
      survival.
AB  - The stringent response utilizes hyperphosphorylated guanine [(p)ppGpp] as a
      signaling molecule to control bacterial gene expression involved in long-term
      survival under starvation conditions. In gram-negative bacteria, (p)ppGpp is
      produced by the activity of the related RelA and SpoT proteins. Mycobacterium
      tuberculosis contains a single homolog of these proteins (Rel(Mtb)) and responds
      to nutrient starvation by producing (p)ppGpp. A rel(Mtb) knockout strain was
      constructed in a virulent strain of M. tuberculosis, H37Rv, by allelic
      replacement. The rel(Mtb) mutant displayed a significantly slower aerobic growth
      rate than the wild type in synthetic liquid media, whether rich or minimal. The
      growth rate of the wild type was equivalent to that of the mutant when citrate or
      phospholipid was employed as the sole carbon source. These two organisms also
      showed identical growth rates within a human macrophage-like cell line. These
      results suggest that the in vivo carbon source does not represent a stressful
      condition for the bacilli, since it appears to be utilized in a similar Rel(Mtb)
      independent manner. In vitro growth in liquid media represents a condition that
      benefits from Rel(Mtb)-mediated adaptation. Long-term survival of the rel(Mtb)
      mutant during in vitro starvation or nutrient run out in normal media was
      significantly impaired compared to that in the wild type. In addition, the mutant
      was significantly less able to survive extended anaerobic incubation than the
      wild-type virulent organism. Thus, the Rel(Mtb) protein is required for long-term
      survival of pathogenic mycobacteria under starvation conditions.

PMID- 10940035
TI  - Domain structure of Salmonella FlhB, a flagellar export component responsible for
      substrate specificity switching.
AB  - We have investigated the properties of the cytoplasmic domain (FlhB(C)) of the
      383-amino-acid Salmonella membrane protein FlhB, a component of the type III
      flagellar export apparatus. FlhB, along with the hook-length control protein
      FliK, mediates the switching of export specificity from rod- and hook-type
      substrates to filament-type substrates during flagellar morphogenesis. Wild-type
      FlhB(C) was unstable (half-life, ca. 5 min), being specifically cleaved at Pro
      270 into two polypeptides, FlhB(CN) and FlhB(CC), which retained the ability to
      interact with each other after cleavage. Full-length wild-type FlhB was also
      subject to cleavage. Coproduction of the cleavage products, FlhB(delta CC) (i.e.,
      the N-terminal transmembrane domain FlhB(TM) plus FlhB(CN)) and FlhB(CC),
      resulted in restoration of both motility and flagellar protein export to an flhB
      mutant host, indicating that the two polypeptides were capable of productive
      association. Mutant FlhB proteins that can undergo switching of substrate
      specificity even in the absence of FliK were much more resistant to cleavage
      (half-lives, 20 to 60 min). The cleavage products of wild-type FlhB(C), existing
      as a FlhB(CN)-FlhB(CC) complex on an affinity blot membrane, bound the rod- and
      hook-type substrate FlgD more strongly than the filament-type substrate FliC. In
      contrast, the intact form of FlhB(C) (mutant or wild type) or the FlhB(CC)
      polypeptide alone bound FlgD and FliC to about the same extent. FlhB(CN) by
      itself did not bind substrates appreciably. We propose that FlhB(C) has two
      substrate specificity states and that a conformational change, mediated by the
      interaction between FlhB(CN) and FlhB(CC), is responsible for the specificity
      switching process. FliK itself is an export substrate; its binding properties for
      FlhB(C) resemble those of FlgD and do not provide any evidence for a physical
      interaction beyond that of the export process.

PMID- 10940034
TI  - Role of a Candida albicans P1-type ATPase in resistance to copper and silver ion
      toxicity.
AB  - Copper ion homeostasis is complicated in that copper is an essential element
      needed for a variety of cellular processes but is toxic at excess levels. To
      identify Candida albicans genes that are involved in resistance to copper ion
      toxicity, a library containing inserts of C. albicans genomic DNA was used to
      complement the copper sensitivity phenotype of a Saccharomyces cerevisiae
      cup1Delta strain that is unable to produce Cup1p, a metallothionein (MT)
      responsible for high-level copper ion resistance. A P1-type ATPase (CPx type)
      that is closely related to the human Menkes and Wilson disease proteins was
      cloned. The gene encoding this pump was termed CRD1 (for copper resistance
      determinant). A gene encoding a 76-amino-acid MT similar to higher eukaryotic MTs
      in structure was also cloned, and the gene was termed CRD2. Transcription of the
      CRD1 gene was found to increase upon growth with increasing copper levels, while
      the CRD2 mRNA was expressed at a constant level. Strains with the CRD1 gene
      disrupted were extremely sensitive to exogenous copper and failed to grow in
      medium containing 100 microM CuSO(4). These crd1 strains also exhibited increased
      sensitivity to silver and cadmium, indicating that Crd1p is somewhat promiscuous
      with respect to metal ion transport. Although strains with the CRD2 gene
      disrupted showed reduced growth rate with increasing copper concentration, the
      crd2 mutants eventually attained wild-type levels of growth, demonstrating that
      CRD2 is less important for resistance to copper ion toxicity. Crd1p is the first
      example of a eukaryotic copper pump that provides the primary source of cellular
      copper resistance, and its ability to confer silver resistance may enhance the
      prevalence of C. albicans as a nosocomial pathogen.

PMID- 10940036
TI  - A scaffoldin of the Bacteroides cellulosolvens cellulosome that contains 11 type
      II cohesins.
AB  - A cellulosomal scaffoldin gene, termed cipBc, was identified and sequenced from
      the mesophilic cellulolytic anaerobe Bacteroides cellulosolvens. The gene encodes
      a 2,292-residue polypeptide (excluding the signal sequence) with a calculated
      molecular weight of 242,437. CipBc contains an N-terminal signal peptide, 11 type
      II cohesin domains, an internal family III cellulose-binding domain (CBD), and a
      C-terminal dockerin domain. Its CBD belongs to family IIIb, like that of CipV
      from Acetivibrio cellulolyticus but unlike the family IIIa CBDs of other
      clostridial scaffoldins. In contrast to all other scaffoldins thus far described,
      CipBc lacks a hydrophilic domain or domain X of unknown function. The singularity
      of CipBc, however, lies in its numerous type II cohesin domains, all of which are
      very similar in sequence. One of the latter cohesin domains was expressed, and
      the expressed protein interacted selectively with cellulosomal enzymes, one of
      which was identified as a family 48 glycosyl hydrolase on the basis of partial
      sequence alignment. By definition, the dockerins, carried by the cellulosomal
      enzymes of this species, would be considered to be type II. This is the first
      example of authentic type II cohesins that are confirmed components of a
      cellulosomal scaffoldin subunit rather than a cell surface anchoring component.
      The results attest to the emerging diversity of cellulosomes and their component
      sequences in nature.

PMID- 10940037
TI  - Cell-associated pheromone peptide (cCF10) production and pheromone inhibition in
      Enterococcus faecalis.
AB  - In Enterococcus faecalis, the peptide cCF10 acts as a pheromone, inducing
      transfer of the conjugative plasmid pCF10 from plasmid-containing donor cells to
      plasmid-free recipient cells. In these studies, it was found that a substantial
      amount of cCF10 associates with the envelope of the producing cell. Pheromone
      activity was detected in both wall and membrane fractions, with the highest
      activity associated with the wall. Experiments examining the effects of protease
      inhibitor treatments either prior to or following cell fractionation suggested
      the presence of a cell envelope-associated pro-cCF10 that can be processed to
      mature cCF10 by a maturase or protease. A pCF10-encoded membrane protein, PrgY,
      was shown to prevent self-induction of donor cells by reducing the level of
      pheromone activity in the cell wall fraction.

PMID- 10940038
TI  - Effects of limited aeration and of the ArcAB system on intermediary pyruvate
      catabolism in Escherichia coli.
AB  - The capacity of Escherichia coli to adapt its catabolism to prevailing redox
      conditions resides mainly in three catabolic branch points involving (i) pyruvate
      formate-lyase (PFL) and the pyruvate dehydrogenase complex (PDHc), (ii) the
      exclusively fermentative enzymes and those of the Krebs cycle, and (iii) the
      alternative terminal cytochrome bd and cytochrome bo oxidases. A quantitative
      analysis of the relative catabolic fluxes through these pathways is presented for
      steady-state glucose-limited chemostat cultures with controlled oxygen
      availability ranging from full aerobiosis to complete anaerobiosis. Remarkably,
      PFL contributed significantly to the catabolic flux under microaerobic conditions
      and was found to be active simultaneously with PDHc and cytochrome bd oxidase
      dependent respiration. The synthesis of PFL and cytochrome bd oxidase was found
      to be maximal in the lower microaerobic range but not in a delta ArcA mutant, and
      we conclude that the Arc system is more active with respect to regulation of
      these two positively regulated operons during microaerobiosis than during
      anaerobiosis.

PMID- 10940039
TI  - Expression of a constitutively active Cdc42 homologue promotes development of
      sclerotic bodies but represses hyphal growth in the zoopathogenic fungus
      Wangiella (Exophiala) dermatitidis.
AB  - In contrast to the CDC42 homologues of Saccharomyces cerevisiae and
      Schizosaccharomyces pombe, the WdCDC42 gene in the human pathogenic fungus
      Wangiella (Exophiala) dermatitidis was found to be nonessential for cell
      viability. Expression of the constitutively active allele wdcdc42(G14V) at 37
      degrees C induced nonpolarized growth that led to cell enlargement and multiple
      nucleation. The swollen cells subsequently converted into planate divided
      bicellular forms or multiply septated sclerotic bodies in post-log phase, when
      the G14V-altered protein was diminished. The wdcdc42(G14V) mutation also strongly
      repressed filamentous growth both in the wild-type strain and in the temperature
      sensitive hyphal-form mutant Hf1. In contrast, overexpression of the dominant
      negative alleles wdcdc42(T19N) and wdcdc42(D120A) had no obvious effect on fungal
      cell polarization. These results suggested that WdCdc42p plays a unique
      regulatory role in cellular morphogenesis in W. dermatitidis. Activation of this
      protein in response to extracellular or intracellular signals seems to commit its
      yeast-like cells to a phenotype transition that produces sclerotic bodies while
      repressing hyphal development.

PMID- 10940040
TI  - Halocin S8: a 36-amino-acid microhalocin from the haloarchaeal strain S8a.
AB  - Halocin S8 is a hydrophobic microhalocin of 36 amino acids (3,580 Da) and is the
      first microhalocin to be described. This peptide antibiotic is unique since it is
      processed from inside a much larger, 33,962-Da pro-protein. Halocin S8 is quite
      robust, as it can be desalted, boiled, subjected to organic solvents, and stored
      at 4 degrees C for extended periods without losing activity. The complete amino
      acid sequence of halocin S8 was obtained first by Edman degradation of the
      purified protein and verified from the halS8 gene: H(2)N-S-D-C-N-I-N-S-N-T-A-A-D
      V-I-L-C-F-N-Q-V-G-S-C-A-L-C-S-P-T-L-V-G -G-P-V-P-COOH. The halS8 gene is encoded
      on an approximately 200-kbp megaplasmid and contains a 933-bp open reading frame,
      of which 108 bp are occupied by halocin S8. Both the halS8 promoter and the
      "leaderless" halS8 transcript are typically haloarchaeal. Northern blot analysis
      revealed three halS8 transcripts: two abundant and one minor. Inspection of the
      3' end of the gene showed only a single, weak termination site (5'-TTTAT-3'),
      suggesting that some processing of the larger transcripts may be involved.
      Expression of the halS8 gene is growth stage dependent: basal halS8 transcript
      levels are present in low concentrations during exponential growth but increase
      ninefold during the transition to stationary phase. Initially, halocin activity
      parallels halS8 transcript levels very closely. However, when halocin activity
      plateaus, transcripts remain abundant, suggesting inhibition of translation at
      this point. Once the culture enters stationary phase, transcripts rapidly return
      to basal levels.

PMID- 10940041
TI  - Genetic evidence that transcription activation by RhaS involves specific amino
      acid contacts with sigma 70.
AB  - RhaS activates transcription of the Escherichia coli rhaBAD and rhaT operons in
      response to L-rhamnose and is a member of the AraC/XylS family of transcription
      activators. We wished to determine whether sigma(70) might be an activation
      target for RhaS. We found that sigma(70) K593 and R599 appear to be important for
      RhaS activation at both rhaBAD and rhaT, but only at truncated promoters lacking
      the binding site for the second activator, CRP. To determine whether these
      positively charged sigma(70) residues might contact RhaS, we constructed alanine
      substitutions at negatively charged residues in the C-terminal domain of RhaS.
      Substitutions at four RhaS residues, E181A, D182A, D186A, and D241A, were
      defective at both truncated promoters. Finally, we assayed combinations of the
      RhaS and sigma(70) substitutions and found that RhaS D241 and sigma(70) R599 met
      the criteria for interacting residues at both promoters. Molecular modeling
      suggests that sigma(70) R599 is located in very close proximity to RhaS D241;
      hence, this work provides the first evidence for a specific residue within an
      AraC/XylS family protein that may contact sigma(70). More than 50% of AraC/XylS
      family members have Asp or Glu at the position of RhaS D241, suggesting that this
      interaction with sigma(70) may be conserved.

PMID- 10940042
TI  - Understanding the growth phenotype of the yeast gcr1 mutant in terms of global
      genomic expression patterns.
AB  - The phenotype of an organism is the manifestation of its expressed genome. The
      gcr1 mutant of yeast grows at near wild-type rates on nonfermentable carbon
      sources but exhibits a severe growth defect when grown in the presence of
      glucose, even when nonfermentable carbon sources are available. Using DNA
      microarrays, the genomic expression patterns of wild-type and gcr1 mutant yeast
      growing on various media, with and without glucose, were compared. A total of 53
      open reading frames (ORFs) were identified as GCR1 dependent based on the
      criterion that their expression was reduced twofold or greater in mutant versus
      wild-type cultures grown in permissive medium consisting of YP supplemented with
      glycerol and lactate. The GCR1-dependent genes, so defined, fell into three
      classes: (i) glycolytic enzyme genes, (ii) ORFs carried by Ty elements, and (iii)
      genes not previously known to be GCR1 dependent. In wild-type cultures, GCR1
      dependent genes accounted for 27% of the total hybridization signal, whereas in
      mutant cultures, they accounted for 6% of the total. Glucose addition to the
      growth medium resulted in a reprogramming of gene expression in both wild-type
      and mutant yeasts. In both strains, glycolytic enzyme gene expression was induced
      by the addition of glucose, although the expression of these genes was still
      impaired in the mutant compared to the wild type. By contrast, glucose resulted
      in a strong induction of Ty-borne genes in the mutant background but did not
      greatly affect their already high expression in the wild-type background. Both
      strains responded to glucose by repressing the expression of genes involved in
      respiration and the metabolism of alternative carbon sources. Thus, the severe
      growth inhibition observed in gcr1 mutants in the presence of glucose is the
      result of normal signal transduction pathways and glucose repression mechanisms
      operating without sufficient glycolytic enzyme gene expression to support growth
      via glycolysis alone.

PMID- 10940043
TI  - Developmental control of stress stimulons in Streptomyces coelicolor revealed by
      statistical analyses of global gene expression patterns.
AB  - Stress-induced regulatory networks coordinated with a procaryotic developmental
      program were revealed by two-dimensional gel analyses of global gene expression.
      Four developmental stages were identified by their distinctive protein synthesis
      patterns using principal component analysis. Statistical analyses focused on five
      stress stimulons (induced by heat, cold, salt, ethanol, or antibiotic shock) and
      their synthesis during development. Unlike other bacteria, for which various
      stresses induce expression of similar sets of protein spots, in Streptomyces
      coelicolor heat, salt, and ethanol stimulons were composed of independent sets of
      proteins. This suggested independent control by different physiological stress
      signals and their corresponding regulatory systems. These stress proteins were
      also under developmental control. Cluster analysis of stress protein synthesis
      profiles identified 10 different developmental patterns or "synexpression
      groups." Proteins induced by cold, heat, or salt shock were enriched in three
      developmental synexpression groups. In addition, certain proteins belonging to
      the heat and salt shock stimulons were coregulated during development. Thus,
      stress regulatory systems controlling these stimulons were implicated as integral
      parts of the developmental program. This correlation suggested that thermal shock
      and salt shock stress response regulatory systems either allow the cell to adapt
      to stresses associated with development or directly control the developmental
      program.

PMID- 10940045
TI  - Bacillus subtilis comZ (yjzA) negatively affects expression of comG but not comK.
AB  - The yjzA open reading frame, along with med, constitutes an operon. Disruption of
      yjzA caused a five-fold enhancement of comG expression, thereby leading to a
      three-fold-higher transformation efficiency. The expression of comK and the other
      three late competence operons was not affected significantly in the yjzA
      deficient mutant.

PMID- 10940044
TI  - Properties of various Rho1 mutant alleles of Cryptococcus neoformans.
AB  - The RHO1 homologue of Cryptococcus neoformans complemented Saccharomyces
      cerevisiae rho1 mutations. The results of overexpression and site-specific
      mutagenesis of CnRHO1 in C. neoformans and S. cerevisiae indicated that although
      CnRHO1 could functionally substitute for the RHO1 gene of S. cerevisiae, mutants
      of cnrho1 manifested unique features in certain aspects.

PMID- 10940046
TI  - The rel gene is essential for in vitro growth of Staphylococcus aureus.
AB  - The stringent response in Staphylococcus aureus is mediated by the nucleotide
      guanosine pentaphosphate, whose synthesis is catalyzed by the product of the rel
      gene. We report here that the rel gene is essential for the in vitro growth of S.
      aureus, distinguishing it from all other bacteria tested for this requirement.

PMID- 10940047
TI  - Plasmid pGS5 from the hyperthermophilic archaeon Archaeoglobus profundus is
      negatively supercoiled.
AB  - We present evidence that, in contrast to plasmids from other hyperthermophilic
      archaea, which are in the relaxed to positively supercoiled state, plasmid pGS5
      (2.8 kb) from Archaeoglobus profundus is negatively supercoiled. This might be
      due to the presence of a gyrase introducing negative supercoils, since gyrase
      genes are present in the genome of its close relative A. fulgidus, and suggests
      that gyrase activity predominates over reverse gyrase whenever the two
      topoisomerases coexist in cells.

PMID- 10940048
TI  - A family of six flagellin genes contributes to the Caulobacter crescentus
      flagellar filament.
AB  - The Caulobacter crescentus flagellar filament is assembled from multiple
      flagellin proteins that are encoded by six genes. The amino acid sequences of the
      FljJ and FljL flagellins are divergent from those of the other four flagellins.
      Since these flagellins are the first to be assembled in the flagellar filament,
      one or both might have specialized to facilitate the initiation of filament
      assembly.

PMID- 10940049
TI  - Substrate ambiguity of 3-deoxy-D-manno-octulosonate 8-phosphate synthase from
      Neisseria gonorrhoeae revisited.
AB  - Homogeneous, recombinant 3-deoxy-D-manno-octulosonate 8-phosphate synthase from
      Neisseria gonorrhoeae is shown to catalyze the formation of 3-deoxy-D-manno
      octulosonate 8-phosphate from phosphoenolpyruvate and D-arabinose 5-phosphate as
      determined from (1)H-nuclear magnetic resonance analysis of the product. This
      enzyme does not catalyze the condensation of D-erythrose 4-phosphate and
      phosphoenolpyruvate to form 3-deoxy-D-ribo-heptulosonate 7-phosphate, as was
      previously reported (P. S. Subramaniam, G. Xie, T. Xia, and R. A. Jensen, J.
      Bacteriol. 180:119-127, 1998).

PMID- 10940050
TI  - Analysis of tnrA alleles which result in a glucose-resistant sporulation
      phenotype in Bacillus subtilis.
AB  - Bacillus subtilis cells cannot sporulate in the presence of catabolites such as
      glucose. During the analysis of Tn10-generated mutants, we found that deletion of
      the C-terminal region of the tnrA gene, which encodes a global regulator that
      positively regulates a number of genes in response to nitrogen limitation,
      results in a catabolite-resistant sporulation phenotype. Analyses of nrg-lacZ and
      nasB-lacZ, which are activated by TnrA under nitrogen limitation, showed that C
      terminally truncated TnrA activates nitrogen-regulated genes constitutively. The
      relief of catabolite repression of sporulation may result from the uncontrolled
      expression of the TnrA-regulated genes.

PMID- 10940051
TI  - Identification of enzymes homologous to isocitrate dehydrogenase that are
      involved in coenzyme B and leucine biosynthesis in methanoarchaea.
AB  - Two putative Methanococcus jannaschii isocitrate dehydrogenase genes, MJ1596 and
      MJ0720, were cloned and overexpressed in Escherichia coli, and their gene
      products were tested for the ability to catalyze the NAD- and NADP-dependent
      oxidative decarboxylation of DL-threo-3-isopropylmalic acid, threo-isocitrate,
      erythro-isocitrate, and homologs of threo-isocitrate. Neither enzyme was found to
      use any of the isomers of isocitrate as a substrate. The protein product of the
      MJ1596 gene, designated AksF, catalyzed the NAD-dependent decarboxylation of
      intermediates in the biosynthesis of 7-mercaptoheptanoic acid, a moiety of
      methanoarchaeal coenzyme B (7-mercaptoheptanylthreonine phosphate). These
      intermediates included (-)-threo-isohomocitrate [(-)-threo-1-hydroxy-1,2, 4
      butanetricarboxylic acid], (-)-threo-iso(homo)(2)citrate [(-)-threo-1-hydroxy
      1,2,5-pentanetricarboxylic acid], and (-)-threo-iso(homo)(3)citrate [(-)-threo-1
      hydroxy-1,2, 6-hexanetricarboxylic acid]. The protein product of MJ0720 was found
      to be alpha-isopropylmalate dehydrogenase (LeuB) and was found to catalyze the
      NAD-dependent decarboxylation of one isomer of DL-threo-isopropylmalate to 2
      ketoisocaproate; thus, it is involved in the biosynthesis of leucine. The AksF
      enzyme proved to be thermostable, losing only 10% of its enzymatic activity after
      heating at 100 degrees C for 10 min, whereas the LeuB enzyme lost 50% of its
      enzymatic activity after heating at 80 degrees C for 10 min.

PMID- 10940052
TI  - Regulation of cation-coupled high-affinity phosphate uptake in the yeast
      Saccharomyces cerevisiae.
AB  - Studies of the high-affinity phosphate transporters in the yeast Saccharomyces
      cerevisiae using mutant strains lacking either the Pho84 or the Pho89 permease
      revealed that the transporters are differentially regulated. Although both genes
      are induced by phosphate starvation, activation of the Pho89 transporter precedes
      that of the Pho84 transporter early in the growth phase in a way which may
      possibly reflect a fine tuning of the phosphate uptake process relative to the
      availability of external phosphate.

PMID- 10940053
TI  - Glycine betaine transport in the obligate halophilic archaeon Methanohalophilus
      portucalensis.
AB  - Transport of the osmoprotectant glycine betaine was investigated using the
      glycine betaine-synthesizing microbe Methanohalophilus portucalensis (strain
      FDF1), since solute uptake for this class of obligate halophilic methanogenic
      Archaea has not been examined. Betaine uptake followed a Michaelis-Menten
      relationship, with an observed K(t) of 23 microM and a V(max) of 8 nmol per min
      per mg of protein. The transport system was highly specific for betaine: choline,
      proline, and dimethylglycine did not significantly compete for [(14)C]betaine
      uptake. The proton-conducting uncoupler 2, 4-dinitrophenol and the ATPase
      inhibitor N, N-dicyclohexylcarbodiimide both inhibited glycine betaine uptake.
      Growth of cells in the presence of 500 microM betaine resulted in faster cell
      growth due to the suppression of the de novo synthesis of the other compatible
      solutes, alpha-glutamate, beta-glutamine, and N(epsilon)-acetyl-beta-lysine.
      These investigations demonstrate that this model halophilic methanogen, M.
      portucalensis strain FDF1, possesses a high-affinity and highly specific betaine
      transport system that allows it to accumulate this osmoprotectant from the
      environment in lieu of synthesizing this or other osmoprotectants under high-salt
      growth conditions.

PMID- 10940055
TI  - Millenium paper: history of dermatologic cryosurgery.

PMID- 10940054
TI  - Reduction of GC --> TA transversion mutation by overexpression of MutS in
      Escherichia coli K-12.
AB  - Overexpression of the MutS repair protein significantly decreased the rate of
      lacZ GC --> TA transversion mutation in stationary-phase and exponentially
      growing bacteria and in mutY and mutM mutants, which accumulate mismatches
      between 8-oxoguanine (8-oxoG) and adenine residues in DNA. Conversely, GC --> TA
      transversion increased in mutL or mutS mutants in stationary phase. In contrast,
      overexpression of MutS did not appreciably reduce lacZ AT --> CG transversion
      mutation in a mutT mutant. These results suggest that MutS-dependent repair can
      correct 8-oxoG:A mismatches in Escherichia coli cells but may not be able to
      compete with mutation fixation by MutY in mutT mutants.

PMID- 10940056
TI  - Dermatologist and electrologist perspectives on laser procedures by
      nonphysicians.
AB  - BACKGROUND: As hair removal technology continues to evolve and new equipment
      comes to market, conflicts may develop between dermatologists and electrologists
      regarding the professional control and use of these devices. METHODS: A total of
      1004 Fellows of the American Academy of Dermatology and 719 electrologists from
      the southern United States were anonymously surveyed about clinical laser
      procedures (CLPs). RESULTS: Compared to electrologists, dermatologists were more
      likely to support clinical laser regulations that placed licensed physicians in
      control (P =.001) and preferred that a delegating physician be physically present
      on the premises when CLPs were performed (P =.001). If a laser device was
      invented for permanent hair removal that was identical to traditional
      needle/probe electrolysis in every respect except energy type ("laser fiberoptic
      probe," LFP), electrologists were more likely than dermatologists to support
      independent use of this device by electrologists (P =.001). A greater percentage
      of electrologists from Texas, a state without electrolysis licensing, were more
      likely to support the unlicensed use of the LFP and CLPs than electrologists from
      states requiring electrolysis licensing. CONCLUSIONS: These data are consistent
      with previously published literature and permit a greater understanding of the
      multiple attitudinal, regulatory, and ethical issues involved when considering
      delegated and independent CLPs by electrologists.

PMID- 10940057
TI  - Cryopeeling (extensive cryosurgery) for treatment of actinic keratoses: an update
      and comparison.
AB  - BACKGROUND: The treatment of actinic keratoses is the most common procedure in
      dermatology and liquid nitrogen freezing is the most used method of destruction.
      Yet it is criticized for its limitations of treating only small areas and its
      tendency to leave hypopigmented skin. 5-fluorouracil (5-FU) treatment is also
      widely utilized. It has the advantage of treating large areas, but the
      disadvantages of length of treatment, morbidity, and only partial effectiveness
      in removing deep or hyperkeratotic actinic keratoses. OBJECTIVE: Long-term follow
      up results are reported on the use of extensive cryosurgery to treat areas of
      widespread solar damage. The literature is reviewed comparing the advantages and
      disadvantages versus 5-FU treatment. METHODS: Three hundred and seventy-three
      patients were initially treated for extensive actinic keratoses in a private
      dermatology office in an retirement community in Florida. Individual lesions were
      counted under good lighting conditions with the aid of a 2.5x stereoscopic lens.
      The treated areas were predominately on the face and scalp areas, although some
      arms and hands were treated. A total of 34,604 were initially treated by spraying
      each individual keratosis with liquid nitrogen as well as the entire surrounding
      skin area. RESULTS: The data show that cryopeeling was approximately twice as
      effective as 5-FU when measured at 1-3 years postoperatively. In addition, the
      ease of application, its availability, the low cost of materials, its versatility
      in treating all forms of actinic keratoses, the reduced healing times, and its
      predictably good cosmetic results make this procedure a logical choice for
      treating widespread actinic keratoses. The number of squamous cell carcinoma
      recorded over the entire 6. 5-year study was 33 with no metastases, much lower
      than predicted for patients with actinic keratoses left untreated. CONCLUSION:
      Extensive cryosurgery (cryopeeling) is a highly effective method for removing
      actinic keratoses and preventing recurrences. The subsequent incidence of
      squamous cell carcinoma is also greatly reduced.

PMID- 10940058
TI  - Histologic effect of a variable pulsed Er:YAG laser.
AB  - BACKGROUND: Carbon dioxide (CO2) lasers used for laser resurfacing produce
      significant thermal damage. Short-pulsed Er:YAG lasers provide significant
      control over depth of ablation with minimal thermal damage. Newer combined short
      pulsed/long-pulsed Er:YAG lasers offer the potential for both precise control
      over depth of ablation and degree of chosen thermal damage. OBJECTIVE: To
      determine the correlation between the histologic effects of an ablative short
      pulsed Er:YAG laser and/or a thermally damaging longer-pulsed Er:YAG laser and
      the findings chosen on the touch panel of such a machine. METHODS: In situ lasing
      of abdominoplasty specimens was undertaken. Various depths of ablation and/or
      thermal effect were chosen on the machine. The tissue was laser irradiated,
      histologically analyzed, and ablation/thermal depths of damage were analyzed by a
      blinded dermatopathologist. RESULTS: Postlaser histologic depths of ablation
      after short-pulsed Er:YAG laser resurfacing correlated well with those chosen on
      the machine. However, when a longer, thermally damaging Er:YAG laser pulse was
      chosen, chosen ablative and/or thermal depths of damage showed histologic
      correlation only for the first pass. With repeated passes, using the variable
      pulse width, the histologic depth of ablation and residual thermal damage do not
      match the settings on the machine. CONCLUSION: A dual-mode Er:YAG laser provides
      the histologic control over depth of ablation seen with all short-pulsed Er:YAG
      lasers. In addition, the histologic thermal effect desired from CO2 lasers could
      be observed when such a system is used with longer Er:YAG laser pulses. Good
      correlation between chosen laser parameters and histologic findings are seen with
      all chosen levels of short-pulsed Er:YAG laser parameters. Good correlation is
      seen between the chosen laser parameters and histologic findings after a first
      pass of either a longer pulsed thermal damaging Er:YAG laser alone or in
      combination with a shorter pulsed ablative Er:YAG laser. However, subsequent
      laser passes in these modes showed poor correlation between the chosen laser
      parameters and histologic effect. Such findings have important implications when
      such a laser is used clinically.

PMID- 10940059
TI  - Treatment of pseudofolliculitis barbae using the Q-switched Nd:YAG laser with
      topical carbon suspension.
AB  - BACKGROUND: Pseudofolliculitis barbae (PFB) is a condition caused by ingrown
      hairs of the face. No treatment to date has shown long-term effectiveness without
      risk of side effects or ease of treatment. OBJECTIVE: The goal of this pilot
      study was to evaluate the use of the topical suspension-assisted Q-switched
      Nd:YAG laser in the treatment of PFB. METHODS: Nine patients were given two
      treatments 1 month apart and assessed by objective papule/pustule counts at 1 and
      2 months after final treatment. Treatment sites were 9 cm2 regions on the
      mandible and neck, with contralateral controls. Patients also performed
      subjective evaluations. RESULTS: Reduction in the quantity of papules and
      pustules when compared with baseline was statistically significant for treatment
      of the mandibular region and combined sites at 1- and 2-month evaluations, as
      well as the neck region at the 2-month evaluation. CONCLUSION: Use of the Q
      switched Nd:YAG laser with topical carbon suspension is an effective means of
      treating PFB, with results persisting at least 2 months after treatment.

PMID- 10940060
TI  - An in vivo trial comparing the use of different types of 532 nm Nd:YAG lasers in
      the treatment of facial lentigines in Oriental patients.
AB  - BACKGROUND: Versapulse is a system that consists of four laser modalities and was
      developed with the aim of increasing cost-effectiveness. However, as these lasers
      share a common power supply, for the Q-switched (QS) Nd:YAG 532 nm laser a large
      spot diameter is necessary to lower the fluence to a suitable level. This can
      increase the risk of hyperpigmentation when used for the treatment of lentigines
      in dark-skinned patients. OBJECTIVE: The aim of our study was to access the
      clinical efficacy and the complication rate of the Versapulse QS Nd:YAG 532 nm
      laser, the Versapulse long-pulsed Nd:YAG 532 nm laser (without the chill tip),
      and a conventional QS Nd:YAG 532 nm laser in the treatment of lentigines in
      Chinese patients. METHODS: Thirty-four Chinese patients with lentigines were
      randomized to receive laser surgery, with one side of the face treated by one
      laser and the other side treated by a different system. Patients were monitored
      for 6 weeks to assess the degree of clearing, hyperpigmentation,
      hypopigmentation, and erythema. Assessments involved patients interviewed using a
      visual analog questionnaire and two blinded observers who evaluated the pre- and
      posttreatment clinical photographs. RESULTS: The Versapulse QS Nd:YAG 532 nm
      laser was associated with a statistically higher risk of complications. The
      Versapulse long-pulsed Nd:YAG 532 nm laser was compatible with the conventional
      QS Nd:YAG 532 nm laser in terms of clinical efficacy and complication rates.
      CONCLUSION: The Versapulse long-pulsed 532 nm laser is more effective and should
      be used instead of the Versapulse QS Nd:YAG 532 nm laser for the treatment of
      lentigines in dark-skinned patients.

PMID- 10940061
TI  - Performance comparison of nylon and an absorbable suture material (Polyglactin
      910) in the closure of punch biopsy sites.
AB  - The ability to close biopsy sites primarily without the need for removing sutures
      is obvious. However, it was unclear whether absorbable sutures could be used for
      this purpose. We prospectively studied 10 healthy volunteers on whom one 3 mm
      punch biopsy was performed on each arm. In each subject two sutures were compared
      for closure of the biopsy sites, polyglactin 910 and nylon. Our primary goal was
      to compare absorbable and nonabsorbable sutures in the closure of punch biopsy
      sites. Each site was closed with one simple percutaneous suture. The sites were
      evaluated at 2 weeks and 6 months for redness, infection, dehiscence, scar
      hypertrophy, and patient satisfaction. We found no statistically significant
      difference between the two suture materials in any of the above parameters.
      Therefore we conclude that absorbable sutures are a good alternative in the
      primary closure of skin biopsy sites.

PMID- 10940062
TI  - Suction blister induction time: 15 minutes or 150 minutes?
AB  - BACKGROUND: The literature on suction blister is somewhat confusing regarding
      suction blister induction time (SBIT). To date, various factors influencing the
      SBIT have not been discussed comprehensively. OBJECTIVE: To determine the effect
      of diameter of suction syringes/cups on SBIT and review the factors influencing
      SBIT. METHODS: Five young patients (four females, one male; age range 16-27
      years, average age 23 years) were selected for the study. Five suction syringes
      of 2, 5, 10, 20, and 50 ml capacity (diameter 1, 1. 4, 1.7, 2.2, and 3.2 cm,
      respectively) were applied on the lateral aspect of the thigh and observed for
      production of unilocular blister at 15 minute intervals. RESULTS: The average
      SBIT was 63, 72, 98, 123, and 208 minutes in 2, 5, 10, 20, and 50 ml syringes,
      respectively. CONCLUSIONS: The SBIT is directly proportional to the diameter of
      the suction syringe. A literature review suggests that the site of the suction
      blister, age of the subject, amount of vacuum created, temperature, intradermal
      injection of saline, corticosteroid-induced atrophy, and pretreatment of the site
      with PUVA are the important factors influencing the SBIT. Use of 10 or 20 ml
      syringes as suction cups and -300 mmHg pressure are appropriate choices for
      suction blister induction and produce blisters in about 1-2 hours.

PMID- 10940063
TI  - Cosmetic results of cryosurgery versus surgical excision for primary
      uncomplicated basal cell carcinomas of the head and neck.
AB  - BACKGROUND: The incidence of multiple facial basal cell carcinomas (BCCs) is
      increasing. OBJECTIVE: Comparison of cosmetic results after cryosurgery and
      excision for primary BCCs. METHODS: Cosmetic results after cryosurgery and
      excision (prospective randomized study) of primary BCCs in the head/neck area
      were assessed by five independent professional observers and by the patients.
      RESULTS: Ninety-six BCCs were treated either with surgical excision (n = 48) or
      cryosurgery (n = 48). Clinical professionals evaluated the cosmetic results after
      surgery as significantly better. The beautician had no preference for either
      therapy. The patient had a significant preference for excision. Localization and
      size of the tumor did not modify this general preference for excision. The male
      dermatologist, however, had a tendency to evaluate results in the cheek,
      periauricular, and neck area as inferior to those in the rest of the face,
      regardless of which therapy was given. CONCLUSION: In general, cosmetic results
      after excision are better than after cryosurgery.

PMID- 10940065
TI  - Mohs micrographic excision of melanoma using immunostains.
AB  - BACKGROUND: Mohs excision of melanoma remains controversial, in part because of
      concerns regarding evaluation of frozen section margins. Several
      immunohistochemical stains are available for melanoma that can be used on frozen
      sections. OBJECTIVE: To review our experience with Mohs micrographic excision of
      melanoma using immunostains. METHODS: Sixty-eight patients were treated,
      including 46 with melanoma in situ and 22 with invasive melanoma, 62 of which
      were on the head or neck. HMB-45, MEL-5, Melan-A (A-103), and S-100 stains were
      employed. RESULTS: Sixty-seven of 68 tumors were excised to clear margins,
      requiring an average of 2.0 layers. Immunostains greatly enhanced detection of
      melanoma on frozen sections. The average margin required for clearance of in situ
      melanoma was 8.3 mm and of invasive melanoma was 11.1 mm. Only 23 of 46 (50%) in
      situ melanomas were clear with < or =6 mm margins; 15 mm margins were required to
      clear 96% of the tumors. Eleven of 22 (50%) invasive melanomas were clear with <
      or =6 mm margins; 26 mm margins were required to clear 95% of the tumors. Melan-A
      (A-103) was the most consistently crisp and easily interpreted immunostain.
      CONCLUSIONS: Mohs excision of melanoma using immunostains can be useful,
      especially for tumors on the head and neck. For routine excision, margins wider
      than those currently recommended may be required to ensure tumor clearance. We
      recommend that (1) biopsies be stained preoperatively for Melan-A and/or HMB-45,
      (2) a debulking layer be obtained for permanent sections prior to Mohs layers,
      and positive and negative control specimens from the tumor and distant skin
      should be employed for comparison of staining patterns. Large-scale prospective
      studies of in situ and invasive melanoma on the head and neck are necessary.

PMID- 10940064
TI  - Photodynamic therapy of cutaneous lymphoma using 5-aminolevulinic acid topical
      application.
AB  - BACKGROUND: Photodynamic therapy (PDT) with topical application of 5
      aminolevulinic acid (ALA) is a new and effective modality for treatment of
      superficial basal and squamous cell carcinomas. OBJECTIVE: We present the
      kinetics of ALA-induced protoporphyrin IX (PP) accumulation and the results of
      ALA PDT treatment on two patients with different stages (stage I and stage III)
      of mycosis fungoides (MF)-type cutaneous T-cell lymphoma (CTCL). METHODS: ALA
      Decoderm cream was applied to the lesions for 16 hours. Spectrofluorescence
      measurements of PP accumulation were carried out before, during, and 1 hour after
      photoirradiation (580-720 nm) using the VersaLight system. RESULTS: Different
      patterns of PP fluorescence kinetics were observed in patients with early and
      advanced stages of the disease. During photoirradiation the intensity of
      fluorescence decreased depending on the lesion thickness. One hour after the
      photoirradiation procedure no PP fluorescence was observed in the stage I MF
      lesion, while in the thick stage III MF lesions, PP fluorescence reappeared;
      after an additional 10-15 minutes of irradiation PP fluorescence disappeared.
      Complete response with excellent cosmetic results was observed in the stage I
      lesion after a single irradiation with a light dose of 170 J/cm2; in five stage
      III lesions, complete response was achieved after fractionated irradiation with a
      total light dose of 380 J/cm2 (follow-up at 27 and 24 months, respectively).
      CONCLUSION: The results showed a high response of both stage I and stage III MF
      lesions to ALA PDT. This modality appears to be very effective and can be used
      successfully for MF treatment.

PMID- 10940066
TI  - Postoperative stroke after stopping warfarin for cutaneous surgery.
AB  - BACKGROUND: Two patients undergoing cutaneous surgery had thromboembolic strokes
      within 1 week after surgery. Both patients had been taking warfarin for
      prevention of thromboembolism and warfarin was stopped 3-7 days prior to surgery.
      OBJECTIVE: To examine the rationale and problems associated with preoperative
      warfarin discontinuation. METHODS: Review of the medical literature. RESULTS:
      When warfarin is stopped prior to surgery and restarted soon after surgery, the
      patient is at increased risk for thromboembolism. Although it is commonly
      believed that continuing warfarin during surgery is associated with an increased
      bleeding risk, for cutaneous surgery, this risk is extremely low and can be
      easily managed. CONCLUSION: Warfarin should not be discontinued prior to
      cutaneous surgery because of the risk of thromboembolic stroke.

PMID- 10940067
TI  - Corrective photoepilation for improper hairline placement after hair
      transplantation.
AB  - BACKGROUND: Noncoherent filtered flashlamp pulsed light has not been used for
      correction of surgical problems after hair transplantation. OBJECTIVE: To
      evaluate the clinical results of photoepilation in a patient with improper
      hairline placement after hair transplantation. METHODS: A noncoherent filtered
      flashlamp pulsed light source was used to photoepilate the misplaced frontal
      hairline in a 37-year-old Caucasian man, skin phototype IV (Fitzpatrick scale),
      who suffered from common baldness grade IV (Ebling scale) and had undergone a
      hair transplant 6 years before. The frontal hairline received three treatment
      sessions at 2-month intervals with the following treatment parameters: 695 nm
      cutoff filter, fluence 38 J/cm2, 3.5-msec pulse duration, triple-pulse mode, and
      30-msec delay. The gulfs received two treatment sessions with the same protocol.
      RESULTS: Final clinical aspect was good and no hair regrowth in the frontal
      hairline has been observed after 1.5 years of follow-up. CONCLUSION: Noncoherent
      filtered flashlamp pulsed light is a novel therapeutic choice that offers a
      nonsurgical solution to unnatural hairline after hair transplantation.

PMID- 10940068
TI  - Successful correction of depressed scars of the forehead secondary to trauma and
      morphea en coup de sabre by en bloc autologous dermal fat graft.
AB  - BACKGROUND: Atrophic scars of the forehead can result from various pathologic
      processes including morphea en coup de sabre as well as trauma. A variety of
      surgical techniques can be used to correct these atrophic scars. OBJECTIVE: Soft
      tissue augmentation for correction of atrophic scars of the forehead using en
      bloc autologous dermal fat graft. METHODS: Use of en bloc autologous dermal fat
      graft harvested from the hip and inserted into a pocket created under the
      atrophic scar in two patients with depressed scars of the forehead. RESULTS:
      Overcorrection of the scars with en bloc autologous dermal fat grafts resulted in
      the treated areas becoming level with the adjacent skin within 3 months. Follow
      up for a period of 12 months showed a perfectly level and stable graft with no
      further resorption. CONCLUSION: En bloc autologous dermal fat grafting appears to
      be a safe technique that provides excellent cosmetic results for the correction
      of small to medium depressed scars of the forehead.

PMID- 10940069
TI  - Real photographic prints from digital images.
AB  - BACKGROUND: Digital photography is emerging as a standard method of documenting
      preoperative, intraoperative, and postoperative results in the clinical setting.
      While hard copies of these electronic images can be quickly and easily generated
      on color laser or inkjet printers, there are times when it is necessary to
      generate a true photographic print of an image, either for insurance
      documentation or to meet the publication requirements of a peer-reviewed journal.
      Standard inkjet and laser printers are unable to generate true photographic
      prints. OBJECTIVE: To identify a rapid, cost-effective means of generating high
      quality photographs of digital images. METHODS: We describe the use of on-line
      service bureaus with digital photographic printers to obtain high-quality
      photographic prints of patient images. RESULTS: From as little as 49 cents per
      print, a color or black-and-white print of a color image can be generated by an
      on-line service bureau to satisfy the need for a photographic quality hard copy.
      CONCLUSIONS: While color laser or inkjet printers allow physicians to generate
      their own hard copies of electronic patient images, photographic quality images
      are at times needed to satisfy requirements for insurance documentation or
      publication in peer-reviewed journals. Use of on-line service bureaus is the most
      cost-effective way that we have found to obtain high-quality photographic color
      or black-and-white prints from electronically stored patient images.

PMID- 10940070
TI  - A technique for hair-grafting in between existing follicles in patients with
      early pattern baldness.
AB  - BACKGROUND: When using follicular hair transplantation on patients with early
      male or female pattern baldness, there can be significant trauma to preexisting
      hair follicles. This becomes especially important in view of the fact that
      finastride and minoxidil can stop or slow hair loss. OBJECTIVE: To develop a
      system that averts damage to preexisting hair follicles in patients with early
      male or female pattern baldness. METHODS: A Lutex headlight (2.5-3.5x loupe
      magnification system) is used to make 1.0-1.5 mm spear incisions in between the
      hair follicles in patients with early male or female pattern balding.
      Magnification is also utilized during the graft cutting and placement phases of
      the operation. RESULTS: This headlight-loupe magnification system has
      dramatically decreased the amount of permanent hair loss and anagen effluvium on
      144 patients with early male and female pattern baldness. With less permanent
      hair loss there is greater density observed with each progressive session.
      CONCLUSION: Hair surgeons now have a method to consistently and significantly
      minimize the amount of damage to preexisting hair follicles in patients in the
      early stages of male and female pattern baldness. This becomes even more
      important in light of the fact that more and more patients are using finastride
      or minoxidil to stop the thinning process. Existing hairs can therefore be
      preserved.

PMID- 10940071
TI  - Lessons on dermoscopy #6. Dermatofibroma.

PMID- 10940072
TI  - The current status of sentinel node biopsy in the management of melanoma.

PMID- 10940073
TI  - Regarding cutaneous resurfacing with Er:YAG lasers.

PMID- 10940074
TI  - DEPARTMENTS/LETTER TO THE EDITOR: response:

PMID- 10940075
TI  - Regarding pedunculated malignant melanoma.

PMID- 10940076
TI  - DEPARTMENTS/LETTER TO THE EDITOR: response:

PMID- 10940077
TI  - Mannose binding lectin (MBL) genotype distributions with relation to serum levels
      in UK Caucasoids.
AB  - Mannose binding lectin (MBL) gene and promoter-region polymorphisms contribute to
      a reduction in the levels of circulating MBL in a number of ways. Promoter
      polymorphisms affect the levels of MBL produced, whilst structurally encoding
      mutations cause non-functional protein to be assembled and subsequently degraded.
      MBL is important as a protein of the innate immune system in both the clearance
      of potential pathogens and the activation of the complement cascade. Using
      variations of SSP-PCR amplifications and SSO probing techniques, we have produced
      MBL-polymorphism haplotype and genotype profiles of a series of high-level MBL
      producing, low-level MBL-producing and random individuals taken from a population
      of 800 UK Caucasoid controls. Structurally encoding mutant alleles were more
      frequent within the low-level producing cohort when compared to both high-level
      producers and the randomly selected sample. However, not all low-level producers
      could be accounted for by the possession of low-level encoding haplotypes. This
      may be due to the presence of additional, undetected polymorphisms governing MBL
      production, or another external factor that may influence the transcriptional
      regulation of the gene.

PMID- 10940078
TI  - A novel PCR-RFLP assay for the detection of the single nucleotide polymorphism at
      position -1082 in the human IL-10 gene promoter.

PMID- 10940079
TI  - Common polymorphisms and alternative splicing in the ILT3 gene are not associated
      with atopy.
AB  - Recently, a linkage of the chromosomal region 19q13.4 with bronchial asthma has
      been demonstrated. This region harbours the so-called leucocyte receptor cluster
      with the gene for immunoglobulin-like-transcript 3 (ILT3) as a member. ILT3
      represents an inhibitory receptor bearing three immunoreceptor tyrosine
      inhibitory motifs (ITIM). The protein mediates downregulation of cell activation
      through recruitment of different SH2-containing protein tyrosine phosphatases.
      With regard to the negative immunoregulatory function particularly on B-cells,
      ILT3 represents a candidate gene for atopy and asthma. The aim of this study was
      to screen for common polymorphisms in the gene coding for ILT3 and to test for
      association with the atopic phenotype. Using single-stranded conformal
      polymorphism-analysis and direct genomic sequencing seven polymorphisms, three
      mutations, a common deletion of 7 bp in the third intron and evidence for further
      alternative splicing of the ILT3 gene were found. Although no association was
      found with atopy phenotypes, it might prove useful to test for association with
      bronchial asthma.

PMID- 10940080
TI  - Iron-overload and genotypic expression of HFE mutations H63D/C282Y and
      transferrin receptor Hin6I and BanI polymorphism in german patients with
      hereditary haemochromatosis.
AB  - Gene variations of HFE, a HLA-class I like molecule, are highly associated with
      hereditary haemochromatosis (HH). Functional as well as molecular studies of the
      HFE protein have indicated that the molecule is involved in iron metabolism and
      that the HFE gene variations observed among HH patients affect its interaction
      with the transferrin receptor (TfR). In the present study, we have therefore
      analysed the relationship between the HFE gene variants, C282Y and H63D, and body
      iron status among 85 German HH patients. In addition, two TfR gene polymorphism,
      TfR-Hin6I and TfR-BanI, were typed that have been reported to define ethnically
      distinct haplotypes. As controls we used 251/159 healthy German blood donors.
      Seventy-eight (92%) patients were C292Y homozygous, the H63D mutation was present
      in five (6%) patients with none of the patients being H63D homozygous. Serum
      transferrin, transferrin saturation and liver iron content were determined prior
      to therapeutic intervention. Among C282Y homozygous patients serum ferritin
      levels (2294 +/- 3174 vs. 463 +/- 224 microg L-1, P < 0.0001) and transferrin
      saturation (86 +/- 18% vs. 62 +/- 25%, P = 0.048) were elevated significantly
      compared with C282Y and/or H63D heterozygous patients. In addition, the liver
      iron content (291 +/- 165 vs. 138 +/- 95 micromol g-1, P = 0.028) and liver iron
      index (6.4 +/- 2.8 vs. 3.2 +/- 2.3, P = 0.019) were increased among C282Y
      homozygotes compared with C282Y heterozygotes. In contrast, no difference was
      observed between patients and controls regarding the distribution of TfR-Hin6I
      and TfR-BanI alleles. These data indicate that the iron intake is higher among
      C282Y homozygous patients compared with C282Y heterozygous or C282Y/H63D compound
      heterozygous individuals and supports the functional role of the HFE protein in
      iron metabolism whereas the TfR gene variants seem to have no influence on iron
      uptake.

PMID- 10940081
TI  - A novel locus affecting serum levels of IgG2a maps to the murine H2 region.
AB  - The effects of genes in the murine H2 region on basal immunoglobulin levels were
      investigated and ratios of IgG1/IgG2a were calculated, as low ratios indicate a
      Th1 cytokine mileu. H2b mice with B10 or BALB genetic backgrounds had higher
      levels of IgG2a than H2k and H2d congenic strains, and hence had low IgG1/IgG2a
      ratios. B10 (H2b) mice generally had high levels of IgG2b, IgG3, IgA and IgM, but
      this outcome was more variable. The high IgG2a phenotype was denoted Igis1
      (Immunoglobulin isotype-1) and mapped telomeric of IEbeta using B10.A(4R) mice
      (high IgG2a) and B10.A(3R) and B10.A(5R) mice (low IgG2a). Further mapping in
      B10.A(2R), B10.A(1R) and B10.A(18R) mice placed Igis1 in the 27kb region between
      G7c and G7e.

PMID- 10940082
TI  - CD154 polymorphism in Spanish populations. Differences in the allelic
      distribution between Canary islanders and Peninsulars.
AB  - The CD154 gene contains a dinucleotide repeat (CA)n in the 3' untranslated
      region. Allelic distribution in Spanish populations from two areas with different
      genetic background, the Canary Islands and Peninsula, are described. Seven
      alleles with different allelic distribution between the two groups, were found.
      This represents a highly polymorphic marker, useful for genetic studies on a
      critical molecule in immunity.

PMID- 10940083
TI  - Molecular cloning of a truncated p62Dok1 isoform, p22Dok(del).
AB  - The p21Ras GTPase activating protein-associated 62-kDa protein, p62Dok1, is an
      early substrate of various tyrosine phosphorylation pathways. Its recent cloning
      in human myeloid cells and in murine pre-B cells revealed an N-terminal
      pleckstrin-homology domain and a tyrosine- and proline-rich C-terminal tail in
      its sequence. Here, we characterized a new 1261-bp cDNA identical to that of
      p62Dok1, but with a central 185-bp deletion (bp 456-640). This induced a
      frameshift leading to a premature stop codon. The deduced protein, designated
      p22Dok(del), corresponded to a truncated p62Dok1 isoform of 177 amino acids that
      can be expressed both in vitro and in vivo with an apparent molecular mass of 22
      kDa. This newly identified molecule was composed of the N-terminal PH domain of
      p62Dok1 followed by a new 25-amino acid C-terminal sequence containing a typical
      class II proline-rich motif, suggesting a specific role for p22Dok(del) in signal
      transduction pathways.

PMID- 10940084
TI  - The genomic organization of the mouse CD94 C-type lectin gene.
AB  - The mouse natural killer (NK) gene complex is located on chromosome 6 and
      contains a number of genes encoding C-type lectin receptors which have been found
      to regulate NK cell function. Among these are CD94 and four NKG2 genes. Like its
      human counterpart, the mouse CD94 protein associates with different NKG2 isoforms
      and recognizes the atypical MHC class I molecule Qa-1b. Here, the genomic
      organization of the mouse CD94 gene was determined by analysing a BAC clone
      containing the CD94 gene. The mouse CD94 gene contains six exons separated by
      five introns. Exons I and II encode the 5' untranslated region (UTR) and the
      transmembrane domain. Exon III encodes the stalk region and exons IV-VI encode
      the carbohydrate recognition domain (CRD). Furthermore, we cloned and sequenced
      the CD94 promoter region, and putative regulatory DNA elements were identified.
      Further studies on the CD94 promoter region may help to elucidate the restricted
      expression pattern of CD94 in NK cells and a subpopulation of T cells.

PMID- 10940085
TI  - Prevalence of CCR2-64I, SDF1-3'A and CCR5-Delta32 alleles in healthy Thais.
AB  - A genetic survey was performed of 200 healthy Thai blood donors for the frequency
      of three alleles that influence susceptibility to HIV infection and the rate of
      progression to HIV disease. The CCR5-Delta32 allele was not detected in this
      population. The CCR2-64I allele was detected at a frequency similar to that found
      in other Asian populations (15.7%). SDF1-3'A was detected at 33.2%, supporting a
      cline of increasing frequency of this allele from African and Caucasian to Asian
      (particularly Australasian) populations. These results have implications for the
      role of host genetic background in the biology and pathology of HIV in Thailand,
      and indicate that a systematic survey of non-Caucasian populations may reveal
      novel alleles important in HIV disease.

PMID- 10940086
TI  - Nomenclature for factors of the HLA system, update January 2000.

PMID- 10940087
TI  - Nomenclature for factors of the HLA system, update February 2000.

PMID- 10940088
TI  - Nomenclature for factors of the HLA system, update March 2000.

PMID- 10940089
TI  - Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.
AB  - OBJECTIVES: To determine whether 347 patients would respond to a 50-mg oral dose
      of sumatriptan, even though they considered themselves poor responders to this
      acute therapy for migraine, and to investigate whether oral naratriptan can be an
      effective acute therapy for migraine in the subset of patients who did not
      respond to sumatriptan under double-blind, well-controlled conditions.
      BACKGROUND: Although most migraineurs respond to sumatriptan, there remains a
      need for an effective alternative for those who do not respond. Naratriptan is a
      more potent and more lipophilic member of this class of agent and could prove
      beneficial in such patients. This is the first well-controlled study to assess
      the value of another 5-HT1B/1D agonist in this difficult patient subset. METHODS:
      This study comprised two migraine attacks. The first (attack 1) was a single
      blind assessment of the efficacy of sumatriptan (50 mg orally) in patients with a
      history of poor response to the drug. The second (attack 2) was a randomized,
      parallel group, double-blind, placebo-controlled trial of naratriptan (2.5 mg
      orally) in nonresponders to oral sumatriptan. RESULTS: Attack 1: About two thirds
      of this selected migraine population did not respond to sumatriptan. Attack 2:
      Naratriptan was statistically superior to placebo for headache relief at 2 hours
      and 4 hours, as well as for most other features of migraine attacks. These data
      suggest an intrinsic efficacy of naratriptan in this patient subset and not a
      coincidental response. No unexpected tolerability issues arose. CONCLUSIONS:
      Naratriptan is an alternative therapy for migraineurs who respond poorly to oral
      sumatriptan. No response to one "triptan" does not necessarily predict no
      response to them all.

PMID- 10940090
TI  - Comparative tolerability of oral 5-HT1B/1D agonists.
AB  - OBJECTIVES: To compare the relative tolerability of 5-HT1B/1D agonists and to
      investigate the relationships (if any) among systemic exposure, lipophilicity,
      and clinical tolerability for 5-HT1B/1D agonists. METHODS: Post hoc correlations
      were sought among the following variables: absolute dose (= administered dose x
      oral bioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological
      and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding
      placebo-associated frequencies. RESULTS: For effective doses of all drugs with
      available data, absolute dose-response relationships exist for adverse event
      frequencies. The overall rank order of the frequency of adverse events was as
      follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan. With the
      exception of eletriptan, 5-HT1B/1D agonists exhibit correlations between absolute
      dose, Cmax (R = 0.97), and LogD (R = 0. 71). For neurological and
      dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order
      was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor
      absolute dose size predicted adverse event frequencies. CONCLUSIONS: Triptans may
      be distinguished in terms of their tolerability. Effectiveness, absolute dose
      size, and lipophilicity are related for the 5-HT1B/1D agonists considered here,
      except eletriptan. Adverse event frequencies cannot be predicted from in vitro
      measures of lipophilicity, in vivo estimates of absolute bioavailability, dose
      size, or any combination of these variables. Since these drugs are all agonists
      at 5-HT1B/1D receptors in the low nanomolar range, but differ in their
      tolerability profiles, adverse effects are not likely to be mediated through 5
      HT1B/1D receptors. Drugs of this class must be studied individually and on a
      reasonably large scale in clinical development programs.

PMID- 10940091
TI  - Prevalence and predictors of headaches in US adolescents.
AB  - OBJECTIVES: To examine the prevalence of headaches among US adolescents; to
      explore the differences in prevalence by sex, race, and age; and to test the
      nature of the association between headaches and depression, self-esteem, and
      insomnia. METHODS: This longitudinal study used a nationally representative
      sample of adolescents (n = 6072) who were interviewed in 1995 (wave 1) and then
      interviewed a year later in 1996 (wave 2). Path analyses were used to test for
      the relationships among headaches, insomnia, depression, and self-esteem.
      RESULTS: More than 90% of subjects had experienced one or more headaches during
      the past 12 months. Of that 90%, about 30% reported recurrent headaches occurring
      weekly or more frequently. Girls tended to report more recurrent headaches
      (37.6%) than boys (21.3%). American Indians experienced the highest rate (35. 6%)
      of recurrent headaches followed by white adolescents (32.1%). Depression and low
      self-esteem in wave 1 were found to precede the headaches in wave 2 in girls, but
      not in boys. No causal relationship was found between insomnia and headaches.
      CONCLUSIONS: Headaches are prevalent among US adolescents, especially in girls
      and American Indians. This study suggests the existence of different paths
      involving different factors in headache-presenting behavior for boys and girls.
      Further studies are needed to illustrate the different mechanisms of headache in
      the two sexes.

PMID- 10940092
TI  - Effectiveness of amitriptyline in the prophylactic management of childhood
      headaches.
AB  - OBJECTIVE: To study the effectiveness of a standardized dose of amitriptyline, 1
      mg/kg, for childhood headaches. BACKGROUND: Amitriptyline has been shown to be
      effective for the prophylaxis of migraine in adults. Studies in children,
      however, have been quite limited. In adults, the suggested effective dose range
      is 10 to 150 mg. In children, a standardized dosage is often not used, resulting
      in a dosage range in clinical practice that often varies from a very low dose to
      a dose equivalent to that used in adults. METHODS: Children with more than three
      headaches per month were treated with amitriptyline, slowly increasing the dose
      to 1 mg/kg per day. The frequency, severity, and duration of their headaches were
      initially evaluated and subsequently measured at each follow-up evaluation. Two
      hundred seventy-nine children had headaches occurring frequently enough to
      indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with
      amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The
      ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1
      (+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point
      pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent
      diagnoses using International Headache Society criteria were migraine (60.6%),
      migraine with aura (7.9%), and tension-type headache (10.4%). Of these children,
      146 have been seen for at least one follow-up examination, occurring on average
      67.3 (+/- 32.3) days after beginning prophylactic treatment. RESULTS: A total of
      84.2% of the children reported an overall perception of being better, while 11.6%
      reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0)
      days per month. The average severity was reduced to 5.1 (+/- 2.1), and the
      average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous
      headaches were excluded, the improvements were more marked. Minimal side effects
      were reported from these children and their families. Long-term evaluation (156
      to 415 days) showed continued sustained improvement. CONCLUSIONS: Amitriptyline
      is an effective prophylactic medication for children with frequent headaches. A
      standardized dosing regimen results in a significant number of children
      responding with minimal side effects. The children are able to tolerate this
      dosing scheme and demonstrate good adherence to a dosing schedule of once a day.

PMID- 10940093
TI  - Further development and testing of the migraine-specific quality of life (MSQOL)
      measure.
AB  - OBJECTIVE: To evaluate the longitudinal performance of the migraine-specific
      quality of life (MSQOL) instrument. METHODS: Psychometric tests evaluated data
      obtained from 1383 migraineurs who completed the 20-item MSQOL questionnaire
      during a noncomparative, long-term, observational study of zolmitriptan (Zomig),
      5 mg, for the acute treatment of migraine attacks of any intensity. RESULTS:
      There was a relationship between a history of a high frequency of migraine
      attacks and low baseline MSQOL scores, indicating a lower quality of life.
      Principal components analyses confirmed three domains and an overall score.
      Cronbach alpha coefficients for the overall score (.93) indicated high internal
      consistency. Responsiveness analysis over 180 days of treatment indicated a
      significantly greater improvement in MSQOL scores (P <.05) in treatment
      responders compared with nonresponders. The average effect size (0.25) and Guyatt
      responsiveness statistic (0.46) for the MSQOL instrument exceeded those for the
      eight domains of the Medical Outcomes Study Short Form Health Survey (MOS SF-36)
      (-0.05 to 0.14 and 0.01 to 0.12, respectively). Change from baseline for
      responders in MSQOL total score was 4.7 to 5.4 compared with 1.1 to 2.7 for
      nonresponders. CONCLUSIONS: Cumulative evidence for the MSQOL instrument meets
      established criteria for validity, consistency, and reproducibility and shows
      moderate responsiveness to treatment. This instrument fulfils the need for an
      MSQOL measure to be used as an adjuvant measure in the assessment of long-term
      outcomes of therapy.

PMID- 10940094
TI  - Solubilized ibuprofen: evaluation of onset, relief, and safety of a novel
      formulation in the treatment of episodic tension-type headache.
AB  - OBJECTIVE: To evaluate the relative efficacy of a new solubilized formulation of
      ibuprofen compared with acetaminophen caplets. METHODS: This double-blind,
      randomized, parallel group study evaluated 154 subjects taking a single dose of
      solubilized ibuprofen, 400 mg; acetaminophen, 1000 mg; or placebo for the relief
      of episodic tension-type headache. Time to relief was measured using a stopwatch,
      and overall efficacy was measured using traditional categorical pain and relief
      scales. RESULTS: Ibuprofen capsules (liquigel), 400 mg, were significantly faster
      than both acetaminophen, 1000 mg, and placebo for all time-to-relief measures.
      Ibuprofen liquigel had a median time to first perceptible pain relief of 39
      minutes compared with 47 minutes for acetaminophen and 113 minutes for placebo.
      For median time to meaningful relief, ibuprofen liquigel had a time of 39 minutes
      compared with 53 minutes for acetaminophen and more than 180 minutes for placebo
      (P</=.02 for both measures). In addition, ibuprofen liquigels demonstrated
      significantly superior overall analgesic efficacy compared with acetaminophen,
      1000 mg, for the relief of episodic tension-type headache. Both active treatments
      had a side effect profile similar to placebo. CONCLUSIONS: Although several other
      studies have demonstrated the overall analgesic superiority of ibuprofen to
      acetaminophen, this study demonstrated that the liquigel formulation also
      provides a clinically relevant advantage for time to analgesic effects.

PMID- 10940095
TI  - Assessing the relative incidence of mitochondrial DNA A3243G in migraine without
      aura with maternal inheritance.
AB  - OBJECTIVE: To determine whether patients with migraine without aura with maternal
      "inheritance" are affected by a monosymptomatic form of the MELAS syndrome
      (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) or
      carry the most common mitochondrial DNA (mtDNA) mutation associated with MELAS,
      namely the A3243G transition in the transfer RNA (tRNA)Leu(UUR) gene. BACKGROUND:
      The association between migraine and abnormal mitochondrial function has been
      suggested on clinical, biochemical, and neuroradiological grounds. Migraine
      attacks with vomiting and cerebral infarctions, most often in the posterior
      cerebral regions, which are reminiscent of complicated migraine, are typical
      features of MELAS. The observation that migrainous patients have affected mothers
      more often than affected fathers suggests a possible role for maternally
      transmitted genetic factors. METHODS: We studied 25 patients with migraine with
      aura whose mothers were also affected. A sensitive polymerase chain reaction
      restriction fragment length polymorphism analysis was used to detect mutated
      genomes. CONCLUSIONS: We failed to detect the MELAS mutation, but migraine may
      still be associated with point mutations of mtDNA other than A3243G or with as
      yet-unidentified nuclear DNA factors related to mitochondrial function.

PMID- 10940096
TI  - Venlafaxine extended release (XR) for the prophylaxis of migraine and tension
      type headache: A retrospective study in a clinical setting.
AB  - OBJECTIVE: To assess the efficacy of extended-release venlafaxine in the
      prophylaxis of migraine and chronic tension-type headache. BACKGROUND:
      Venlafaxine, a structurally novel antidepressant, is a selective serotonin
      norepinephrine reuptake inhibitor. This study is the first to test the effects of
      extended-release venlafaxine on headaches. METHODS: Patients were evaluated on a
      retrospective basis. Fifty-six patients with chronic tension-type headache and
      114 patients with migraine were prescribed extended-release venlafaxine. Nearly
      all the study subjects had been resistant to several previous preventive
      medications. Patients took venlafaxine for an average of 6 months with a median
      dose of 150 mg (range, 37.5 to 300 mg). RESULTS: The mean frequency of headaches
      in the group with chronic tension-type headache fell from 24.0 to 15.2 per month
      (P <.0001). The group with migraine showed a reduction from 16.1 to 11.1
      headaches per month (P <.0001). The medicine was well tolerated. CONCLUSIONS:
      This trial indicates that extended-release venlafaxine has potential in headache
      prophylaxis based on its efficacy and safety profile. We recommend a double
      blind, placebo-controlled study to further assess the role of extended-release
      venlafaxine in headache prevention.

PMID- 10940098
TI  - Cardiac risk factors and the use of triptans: a survey study.
AB  - OBJECTIVE: To describe current practice in triptan use. BACKGROUND: Triptans are
      effective migraine treatments that cause chest symptoms in some patients. True
      cardiac ischemia is rare. Design.-Headache specialists and family practitioners
      completed questionnaires regarding the times when triptans are contraindicated,
      obtaining electrocardiograms (ECGs), and giving the first dose in the office.
      RESULTS: Sixty-five headache specialists and 67 family practitioners responded.
      Headache specialists saw an average of 36.3 patients with headache per week.
      Family practitioners saw an average of 7.2. Family practitioners and headache
      specialists had similar opinions regarding the age at which triptans were
      contraindicated with various numbers of risk factors. Sixty-one percent of
      headache specialists and 50% of family practitioners would not use a triptan at
      any age for patients with more than three risk factors (P = NS). Ten percent of
      headache specialists obtained an ECG for all patients being prescribed triptans,
      while no family practitioners did (P =. 008). Ten percent of both family
      practitioners and headache specialists never obtained an ECG, even with multiple
      cardiac risk factors. Headache specialists obtained ECGs more often than family
      practitioners (P <.002 for one to three risk factors). Family practitioners were
      more likely to give the first dose of the triptan in the office regardless of
      cardiovascular risk (58% versus 20%, P <. 001). Forty-five percent of headache
      specialists and 2% of family practitioners never gave the first dose in the
      office (P <.001). Family practitioners gave the first dose in the office more
      readily than headache specialists in patients with no risk factors (P =.001), but
      not for one or more risk factors. CONCLUSIONS: No consensus exists among family
      practitioners or headache specialists about when to avoid using a triptan due to
      excessive cardiac risk factors, when to obtain an ECG prior to using a triptan,
      and when to give the first dose of a triptan in the office. Headache specialists
      are more likely to obtain ECGs, whereas family practitioners are more likely to
      give the first dose of a triptan in the office.

PMID- 10940099
TI  - Olfactory hallucinations during migraine in an adolescent with an MRI temporal
      lobe lesion.
AB  - OBJECTIVE: To report the first example of an abnormal magnetic resonance imaging
      (MRI) test in a patient with migraine and olfactory hallucinations and to provide
      additional evidence for a possible role of the temporal lobe in migraine.
      BACKGROUND: The relationship between the temporal lobe and migraine with or
      without hallucinations is unclear and continues to evolve. Clinical and
      functional neuroimaging studies (positron emission tomography/single photon
      emission computed tomography) have lent support to the possibility of a
      relationship. Anatomical neuroimaging with computed tomography has previously
      been normal. METHODS: The history and findings of an adolescent with migraine and
      olfactory hallucinations is reported. RESULTS: Brain MRI demonstrated a mass in
      the temporal lobe. CONCLUSIONS: Magnetic resonance imaging should be considered
      in patients with olfactory hallucinations and migraine. In addition, the role of
      the temporal lobe in migraine warrants further study.

PMID- 10940100
TI  - Traumatic intracerebral venous thrombosis associated with an abnormal golf swing.
AB  - OBJECTIVES: To describe the occurrence of cerebral venous thrombosis in a 40-year
      old man whose cerebral event was induced by a poor golf swing, to review the
      literature on possible mechanisms producing venous thrombosis, and to compare
      this case with the literature. BACKGROUND: Headache is the most frequent symptom
      in patients with cerebral venous thrombosis. However, patients presenting with a
      headache due to cerebral venous thrombosis are uncommon. The known risk factors
      for thrombosis include both acquired and genetic factors. When the interaction of
      these two groups occurs, the magnitude of this interaction is thought to produce
      a dynamic state that can favor thrombosis. Our case report illustrates that
      moderate levels of anticardiolipin antibodies together with the mild trauma of a
      golf swing can induce a cerebral venous thrombosis. This case also suggests that
      although headache is rarely due to cerebral venous thrombosis, it should be
      excluded by good medical acumen and testing. RESULTS: Minor trauma induced by a
      poor golf swing was chronologically related to the development of a progressive
      cerebral venous thrombosis. The patient had none of the risk factors associated
      with a predisposition to venous thrombosis: hypercoagulable state, concurrent
      infection, pregnancy/puerperium, collagen vascular disorder, malignancy,
      migraine, false-positive VDRL, previous deep vein thrombosis, renal disease,
      factor V Leiden, or a hematological disorder. There was no anatomical abnormality
      that would predispose the patient to a cerebral venous thrombosis. The only
      laboratory abnormality was a moderate anticardiolipin antibody level (25 GPL).
      The patient was placed on warfarin sodium therapy and is currently without
      clinical sequela from the venous thrombotic event. CONCLUSIONS: Under certain
      circumstances, minor trauma can induce cerebral venous thrombosis. A review of
      the literature indicates that cerebral venous thrombosis in the presence of
      anticardiolipin antibodies and in the absence of systemic lupus erythematosus is
      a rare event. Previously, only major traumatic events have been reported to be
      associated with cerebral venous thromboses. The chronological development of
      cerebral venous thrombosis after a faulty golf swing strongly indicates that
      given a background of moderate levels of anticardiolipin antibodies, even minor
      trauma can induce a venous thrombotic event.

PMID- 10940097
TI  - Interobserver reliability in physical examination of the cervical spine in
      patients with headache.
AB  - OBJECTIVE: To assess interobserver reliability of two expert headache
      neurologists when examining the cervical spine of patients with headache.
      BACKGROUND: The diagnosis of cervicogenic headache involves the physical
      examination of the cervical spine. METHODS: Twenty-four patients diagnosed as
      having migraine, tension-type headache, or cervicogenic headache were included in
      the study. After interview, each patient's cervical spine was examined in a
      structured way. Reliability was assessed by Cohen's kappa. RESULTS: Reduced range
      of motion in the cervical spine showed kappa scores indicating moderate
      agreement. Provocation of headache revealed moderate-to-substantial agreement.
      Assessment of zygapophyseal joint pressure pain showed slight-to-fair agreement.
      The kappa values of the circumscribed characteristic tender points showed
      agreement ranging from "not better than chance" to "substantial agreement."
      CONCLUSIONS: Our study showed that the interobserver reliability of expert
      headache neurologists was satisfactory in the majority of the physical
      examination tests of the cervical spine in patients with different headache
      syndromes. However, standardization of the clinical tests in order to improve
      their reliability is recommended.

PMID- 10940102
TI  - Expert opinion: monocular visual aura with headache: retinal migraine?

PMID- 10940101
TI  - Expert opinion: assessing cardiac risk prior to use of triptans.

PMID- 10940105
TI  - Labeling of postconcussion patients as malingering and litigious: a common
      practice in need of criticism.

PMID- 10940103
TI  - Comparison of rizatriptan and sumatriptan: a reply to Tfelt-Hansen et al.

PMID- 10940106
TI  - Worsening of transformed migraine with naratriptan as prophylactic treatment.

PMID- 10940108
TI  - Reflex sympathetic dystrophy.

PMID- 10940109
TI  - Virtual doctors--ready for launching.

PMID- 10940110
TI  - Desideratum dermatologicum: eliminating lipodermatosclerosis; the term and the
      entities.

PMID- 10940111
TI  - Pattern of skin diseases among pilgrims during Hajj season in Makkah, Saudi
      Arabia.
AB  - BACKGROUND: Skin diseases among pilgrims are considered to be one of the possible
      health problems in our area. Data supporting this observation are scanty and
      sparse. The aim of this study was to report the most common skin diseases seen in
      a 15-day period. METHODS: We retrospectively collected all new cases of skin
      diseases diagnosed during a 15-day period at King Faisal Hospital, the nearest
      general medical center to Mina. Pilgrims gather at Mina (which harbors more than
      two million pilgrims every year) to perform their Hajj. RESULTS: During the Hajj
      season in 1998, 731 new patients were seen; 63.3% were men and 36.7% were women.
      Of these cases, Saudi citizens represented 42.5% of the total patients. The peak
      age group ranged from 20 to 39 years. The incidence in Saudi patients was more
      than that in other nationalities. Dermatitis of various etiologies (23.6%) was
      found to be the most common skin disease. Pyoderma was found to be more common in
      Saudis and Asians than in Arabs, whereas Arabs suffered from intertrigo much more
      than Asians and Saudis. CONCLUSIONS: A high incidence of skin diseases such as
      pyoderma and intertrigo among pilgrims of such a large congregation is
      understandable. Investigating these skin infections is worthwhile because they
      are preventable, easily diagnosed, and are curable in the majority of patients.

PMID- 10940112
TI  - Meteorological parameters and the pattern of dermatology clinic attendance
      through a calendar year: a Sri Lankan experience.
AB  - BACKGROUND: Dermatology clinic attendance at a major hospital depends on many
      factors. We planned to determine the monthly variations of skin disease
      presentation and whether there was a correlation between the clinic attendance
      pattern of skin diseases and meteorological parameters. METHODS: The dermatology
      clinic attendance pattern was studied prospectively throughout a calendar year on
      a monthly basis at the dermatology clinic of the General Hospital, Matara, Sri
      Lanka. One thousand and twenty-three consecutive dermatology consultations in the
      private sector were also analyzed for comparison. Meteorological data were
      obtained from the Government Department of Meteorology. RESULTS: A total of 7419
      first visit patients were seen at the general hospital. July and September
      recorded the highest number (718 each) and April recorded the lowest (426). The
      lowest relative humidity was in March (75%) and the highest in October (87%). The
      average maximum temperature ranged from 31.2 degrees C (April) to 29.1 degrees C
      (August, September). Average rainfall was between 622 mm (October) and 59 mm
      (June). Of the diseases considered to have a relationship to meteorological
      parameters, miliaria showed the biggest fluctuation (27 in May to zero in
      August). Photodermatitis was highest in August. The variation in asteatotic
      dermatitis patients was minimal. Dermatitis and fungal diseases comprised over
      50% of clinic attendance throughout the year in both the state and private
      sectors. CONCLUSIONS: Although there were significant fluctuations in several
      disease categories in different months, a clear linear correlation between
      meteorological parameters and the disease presentation pattern could not be
      established. This could be due to the narrow range of variation in the
      meteorological parameters in the geographic area and the multiple variables
      involved in persons presenting to the dermatology clinic.

PMID- 10940113
TI  - Frequency of oral conditions in a dermatology clinic.
AB  - BACKGROUND: Oral mucosal manifestations may be the initial feature, the most
      florid clinical feature, or the only sign of mucocutaneous diseases. METHODS:
      Sixty adult patients (48 women, 12 men) with oral mucous complaints were referred
      to and evaluated at a dermatology clinic in a tertiary care hospital in Mexico
      City between November 1996 and September 1998. RESULTS: The most frequent oral
      conditions observed were pemphigus vulgaris (18.3%), lichen planus (8.3%),
      candidiasis (8.3%), recurrent aphthous ulcers (6.7%), herpetic lesions (6.7%),
      xerostomia (6.7%), and traumatic lesions (6.7%). Oral affection in mucocutaneous
      conditions was observed in 21 (35%) patients; the diagnosis was based on oral
      signs in 10 (48%) of these patients. A large number of oral conditions had
      previously been misdiagnosed. CONCLUSIONS: The importance of the diagnosis of
      oral conditions in dermatology has been underlined in this study due to the
      frequency and diversity of oral lesions. The benefits of an interdisciplinary
      approach in the management of patients has been highlighted.

PMID- 10940114
TI  - American tegumentary leishmaniasis (ATL) in Rio de Janeiro State, Brazil: main
      clinical and epidemiologic characteristics.
AB  - BACKGROUND: Rio de Janeiro State in Brazil is an endemic area of American
      tegumentary leishmaniasis (ATL) induced by Leishmania (Viannia) braziliensis.
      Objective Our purpose was to describe the main clinical and epidemiologic
      characteristics of the disease in Rio de Janeiro State. METHODS: Patients from
      endemic areas of Rio de Janeiro State attending the Evandro Chagas Hospital were
      included in the study. A general physical, dermatologic, and otorhinolaryngologic
      examination was performed in all patients, as well as a Leishmanin skin test.
      Skin biopsy specimens were obtained and utilized for touch preparations (stained
      with Leishman dye), culture in special media (Nicolle, Nevy and McNeal; NNN), and
      histopathologic examination after hematoxylin and eosin stain. Positive cultures
      were identified with regard to species by the isoenzyme technique. Therapy with
      pentavalent antimonial compounds was employed in all cases. Eco-epidemiologic
      characteristics were studied through regular field visits to endemic foci.
      RESULTS: Cutaneous disease was present in 87.2% of patients, and mucosal disease
      in only 12.7%. A single ulcerative cutaneous lesion was the most common clinical
      presentation. Demonstration of the parasite was always difficult and culture in
      special media gave the best results for diagnosis. The species involved in
      transmission was Leishmania (Viannia) braziliensis. Vectors included phlebotomine
      sand flies (Diptera: Psychodidae) of the genus Lutzomyia, and the most common
      species was Lutzomyia intermedia, captured mainly on the external walls of
      houses. CONCLUSIONS: ATL in Rio de Janeiro is mostly a cutaneous disease. In
      general, the cases showed great sensitivity to antimony. A pattern of
      peridomestic transmission seems to be the rule.

PMID- 10940115
TI  - Cost-effective post-exposure prevention of poison ivy dermatitis.
AB  - BACKGROUND: Poison ivy (toxicodendron) dermatitis is the most common allergic
      contact dermatitis in the USA. No studies have shown an effect of washing after a
      short period of time for the prevention of binding of urushiol to the skin.
      Objective To evaluate the efficacy of three different modes of postcontact
      prevention using a surfactant (Dial ultra dishwashing soap), an oil-removing
      compound (Goop), and chemical inactivation (a commercial product Tecnu). METHODS:
      A consented, unsponsored, volunteer experimental study on medical students from
      the University of Missouri School of Medicine, Kansas City. Each subject served
      as his/her own control, comparing four 2.5-cm exposed squares on the inner aspect
      of the forearm, three of which were treated and one untreated. RESULTS:
      Comparisons between the different agents were nonsignificant with P > 0.05. Each
      treatment, however, was significantly improved over the untreated control.
      CONCLUSIONS: Our study showed 70%, 61.8%, and 56. 4% protection with Tecnu, Goop,
      and Dial, respectively, when compared to the positive control, or to the possible
      maximum response, with a cost per ounce (in a local drug and automotive store) of
      $1.25, $0.07, and $0.07, respectively, for a decrease in protection that is
      nonsignificant.

PMID- 10940116
TI  - Infiltrating basal cell carcinoma in the setting of a venous ulcer.
AB  - A 77-year-old man was referred with a 5-year history of an intermittently
      painful, nonhealing right medial ankle ulcer. The ulcer had not responded to
      multiple treatment modalities, including Unna boots, compression therapy,
      sclerotherapy, and split-thickness skin grafting. The past medical history was
      significant for a deep venous thrombosis in the right leg 30 years earlier
      (treated with warfarin for 3 months) and a history of greater saphenous vein
      harvesting for coronary bypass grafting 28 years previously. After the vein
      stripping, the patient had suffered from increasing right leg edema and stasis
      changes in the right leg. His history was also remarkable for coronary artery
      disease, dyslipidemia, and lymphoma treated with chemotherapy 8 years before
      presentation, with no evidence of recurrence. He had stopped smoking
      approximately 20 years earlier. Medications included atenolol, simvastatin,
      nicardipine, nitroglycerin, and aspirin. Skin examination revealed a 3.0 x 3.5-cm
      ulcer adjacent to the medial malleolus. The edges of the ulcer appeared raised
      and rolled (Fig. 1). Centrally, there was granulation tissue, which appeared
      healthy. There were surrounding dermatitic changes. Dorsalis pedis and the
      posterior tibial pulses were normal. Noninvasive vascular studies revealed severe
      venous incompetence of the right popliteal and superficial veins. Arterial
      studies and transcutaneous oximetry were normal. Computed tomographic scan of the
      pelvis did not reveal any adenopathy, and radiographic imaging did not reveal any
      bony changes suggestive of osteomyelitis. Biopsy of the ulcer edge and base
      showed infiltrating basal cell carcinoma (Fig. 2). Mohs' micrographic surgery
      required three layers; the final extent of the ulcer was 7.8 x 6.9 cm. A split
      thickness skin graft was placed.

PMID- 10940117
TI  - A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence
      of past exposure to hepatitis E.

PMID- 10940118
TI  - Papular perniosis mimicking erythema multiforme: the first case report in
      Thailand.

PMID- 10940119
TI  - Tinea manus treated with 1-week itraconazole vs. terbinafine.

PMID- 10940120
TI  - Treatment of scalp seborrheic dermatitis and psoriasis with an ointment of 40%
      urea and 1% bifonazole.

PMID- 10940121
TI  - Clobetasol propionate foam 0.05%: a novel vehicle with enhanced delivery.

PMID- 10940122
TI  - Subcision: a treatment for cellulite.
AB  - BACKGROUND: Cellulite is a common clinical condition, with few proven effective
      therapeutic options. Subcision is a surgical technique that is useful in treating
      advanced degree cellulite. This study was designed to determine the usefulness of
      the treatment of cellulite by subcision. METHODS: From January 1995 to January
      1998, 232 female patients, aged 18-52 years, with cellulite on the thighs and
      buttocks were treated on an outpatient basis by the subcision technique. RESULTS:
      In the postoperative period, all the patients had pain, bruises, and
      hemosiderosis. An improvement in the surface depressions was observed and the
      patients reported a high degree of satisfaction. CONCLUSIONS: This outpatient
      procedure is effective in the correction of surface depressions on the thighs and
      buttocks, clinically classified as cellulite.

PMID- 10940124
TI  - Coexistence of vitiligo and sarcoidosis in a patient with circulating
      autoantibodies.

PMID- 10940123
TI  - A patient with a seborrheic keratosis which caused impaired hearing by closure of
      the external auditory meatus.

PMID- 10940125
TI  - Multiple osteoma cutis lesions associated with acne.

PMID- 10940126
TI  - Bullous pemphigoid possibly triggered and exacerbated by ophthalmic preparations.

PMID- 10940127
TI  - Pagetoid Spitz nevus: a variant of Spitz nevus.

PMID- 10940128
TI  - Mycetoma due to actinomycetes: a rare entity in Europe.

PMID- 10940129
TI  - Managed care, time pressure, and physician job satisfaction: results from the
      physician worklife study.
AB  - OBJECTIVE: To assess the association between HMO practice, time pressure, and
      physician job satisfaction. DESIGN: National random stratified sample of 5,704
      primary care and specialty physicians in the United States. Surveys contained 150
      items reflecting 10 facets (components) of satisfaction in addition to global
      satisfaction with current job, one's career and one's specialty. Linear
      regression-modeled satisfaction (on 1-5 scale) as a function of specialty,
      practice setting (solo, small group, large group, academic, or HMO), gender,
      ethnicity, full-time versus part-time status, and time pressure during office
      visits. "HMO physicians" (9% of total) were those in group or staff model HMOs
      with > 50% of patients capitated or in managed care. RESULTS: Of the 2,326
      respondents, 735 (32%) were female, 607 (26%) were minority (adjusted response
      rate 52%). HMO physicians reported significantly higher satisfaction with
      autonomy and administrative issues when compared with other practice types
      (moderate to large effect sizes). However, physicians in many other practice
      settings averaged higher satisfaction than HMO physicians with resources and
      relationships with staff and community (small to moderate effect sizes). Small
      and large group practice and academic physicians had higher global job
      satisfaction scores than HMO physicians (P <.05), and private practice physicians
      had quarter to half the odds of HMO physicians of intending to leave their
      current practice within 2 years (P <.05). Time pressure detracted from
      satisfaction in 7 of 10 satisfaction facets (P <.05) and from job, career, and
      specialty satisfaction (P <.01). Time allotted for new patients in HMOs (31 min)
      was less than that allotted in solo (39 min) and academic practices (44 min),
      while 83% of family physicians in HMOs felt they needed more time than allotted
      for new patients versus 54% of family physicians in small group practices (P <.05
      after Bonferroni's correction). CONCLUSIONS: HMO physicians are generally less
      satisfied with their jobs and more likely to intend to leave their practices than
      physicians in many other practice settings. Our data suggest that HMO physicians'
      satisfaction with staff, community, resources, and the duration of new patient
      visits should be assessed and optimized. Whether providing more time for patient
      encounters would improve job satisfaction in HMOs or other practice settings
      remains to be determined.

PMID- 10940130
TI  - Effects of the revised HCFA evaluation and management guidelines on inpatient
      teaching.
AB  - OBJECTIVE: In 1996, the Health Care Financing Administration (HCFA) introduced
      new evaluation and management (E&M) guidelines mandating more intensive
      supervision and documentation by attending physicians. We assessed the effects of
      the guidelines on inpatient teaching. DESIGN: Pretest-posttest, nonequivalent
      control group design. SETTING: A university hospital and an affiliated county
      hospital where the guidelines were implemented and an affiliated VA medical
      center where they were not. PARTICIPANTS: Sixty-one full-time faculty who had
      attended on the general medical wards for at least 1 month for 2 of 3 consecutive
      years prior to July 1996 and for at least 1 month during the 18 following months.
      MEASUREMENTS AND MAIN RESULTS: We evaluated standardized, confidential
      evaluations of attending physicians that are routinely completed by residents and
      students after clinical rotations at all three sites. Comparing 863 evaluations
      completed before July 1, 1996 and 497 completed after that date, there were no
      significant differences at any of the hospitals on any items assessed. There were
      also no differences between the university and county hospitals as compared with
      the VA. Eighty-seven percent of 39 university and county attending physicians
      returned a survey about their perceptions of inpatient teaching activities before
      and after July 1, 1996. They reported highly significant increases in time
      devoted to attending responsibilities but diminished time spent on teaching
      activities. CONCLUSIONS: Physicians reported a dramatic increase in overall time
      spent attending but a decrease in time spent teaching following implementation of
      the revised E&M guidelines. Yet, evaluations of their teaching effectiveness did
      not change.

PMID- 10940131
TI  - The effect of medical student teaching on patient satisfaction in a managed care
      setting.
AB  - OBJECTIVE: To measure the effect on patient satisfaction of medical student
      participation in care and the presence of medical student teaching. DESIGN:
      Prospective cohort study. SETTING: Eight outpatient internal medicine departments
      of a university-affiliated HMO in Massachusetts. PATIENTS: Two hundred seven
      patients seen on teaching days (81 patients who saw a medical student-preceptor
      dyad and 126 patients who saw the preceptor alone), and 360 patients who saw the
      preceptor on nonteaching days. Five hundred (88%) of 567 eligible patients
      responded. MEASUREMENTS AND MAIN RESULTS: Thirteen closed-response items on a
      written questionnaire, measuring satisfaction with specific dimensions of care
      and with care as a whole. Visit satisfaction was similar among patients on
      teaching and nonteaching days. Ninety-one percent of patients seeing a medical
      student, 93% of patients seeing the preceptor alone on teaching days, and 93% of
      patients on nonteaching days were satisfied or very satisfied with their visit;
      less than 2% of patients in each group were dissatisfied with their visit.
      Satisfaction on all measured dimensions of care was similar for patients seeing a
      medical student, patients seeing the preceptor alone on teaching days, and
      patients seeing the preceptor on nonteaching days. CONCLUSIONS: Medical student
      participation and the presence of medical student teaching had little effect on
      patient satisfaction. Concerns about patient satisfaction should not prevent
      managed care organizations from participating in primary care education.

PMID- 10940132
TI  - The doctor-patient relationship and HIV-infected patients' satisfaction with
      primary care physicians.
AB  - OBJECTIVE: To assess the extent to which perceptions of specific aspects of the
      doctor-patient relationship are related to overall satisfaction with primary care
      physicians among HIV-infected patients. DESIGN: Longitudinal, observational study
      of HIV-infected persons new to primary HIV care. Data were collected at
      enrollment and approximately 6 months later by in-person interview. SETTING: Two
      urban medical centers in the northeastern United States. PARTICIPANTS: Patients
      seeking primary HIV care for the first time. MEASUREMENTS AND MAIN RESULTS: The
      primary outcome measure was patient-reported satisfaction with a primary care
      physician measured 6 months after initiating primary HIV care. Patients who were
      more comfortable discussing personal issues with their physicians (P =. 021), who
      perceived their primary care physicians as more empathetic (P =.001), and who
      perceived their primary care physicians as more knowledgeable with respect to HIV
      (P =.002) were significantly more satisfied with their primary care physicians,
      adjusted for characteristics of the patient and characteristics of primary care.
      Collectively, specific aspects of the doctor-patient relationship explained 56%
      of the variation in overall satisfaction with the primary care physician.
      CONCLUSIONS: Patients' perceptions of their primary care physician's HIV
      knowledge and empathy were highly related to their satisfaction with this
      physician. Satisfaction among HIV-infected patients was not associated with
      patients' sociodemographic characteristics, HIV risk characteristics, alcohol and
      drug use, health status, quality of life, or concordant patient-physician gender
      and racial matching.

PMID- 10940133
TI  - Confidential clinician-reported surveillance of adverse events among medical
      inpatients.
AB  - BACKGROUND: Although iatrogenic injury poses a significant risk to hospitalized
      patients, detection of adverse events (AEs) is costly and difficult. METHODS: The
      authors developed a confidential reporting method for detecting AEs on a medicine
      unit of a teaching hospital. Adverse events were defined as patient injuries.
      Potential adverse events (PAEs) represented errors that could have, but did not
      result in harm. Investigators interviewed house officers during morning rounds
      and by e-mail, asking them to identify obstacles to high quality care and
      iatrogenic injuries. They compared house officer reports with hospital incident
      reports and patients' medical records. A multivariate regression model identified
      correlates of reporting. RESULTS: One hundred ten events occurred, affecting 84
      patients. Queries by e-mail (incidence rate ratio [IRR] = 0.16; 95% confidence
      interval [95% CI], 0.05 to 0.49) and on days when house officers rotated to a new
      service (IRR = 0.12; 95% CI, 0.02 to 0.91) resulted in fewer reports. The most
      commonly reported process of care problems were inadequate evaluation of the
      patient (16.4%), failure to monitor or follow up (12.7%), and failure of the
      laboratory to perform a test (12.7%). Respondents identified 29 (26. 4%) AEs, 52
      (47.3%) PAEs, and 29 (26.4%) other house officer-identified quality problems. An
      AE occurred in 2.6% of admissions. The hospital incident reporting system
      detected only one house officer-reported event. Chart review corroborated 72.9%
      of events. CONCLUSIONS: House officers detect many AEs among inpatients.
      Confidential peer interviews of front-line providers is a promising method for
      identifying medical errors and substandard quality.

PMID- 10940135
TI  - Evaluation of a national curriculum reform effort for the medicine core
      clerkship.
AB  - BACKGROUND: In 1995, the Society of General Internal Medicine (SGIM) and the
      Clerkship Directors in Internal Medicine (CDIM) developed and disseminated a new
      model curriculum for the medicine core clerkship that was designed to enhance
      learning of generalist competencies and increase interest in general internal
      medicine. OBJECTIVE: To evaluate the dissemination and use of the resulting
      SGIM/CDIM Core Medicine Clerkship Curriculum Guide. DESIGN: Survey of internal
      medicine clerkship directors at the 125 medical schools in the United States.
      MEASUREMENTS AND MAIN RESULTS: The questionnaire elicited information about the
      use and usefulness of the Guide and each of its components, barriers to effective
      use of the Guide, and outcomes associated with use of the Guide. Responses were
      received from 95 clerkship directors, representing 88 (70%) of the 125 medical
      schools. Eighty-seven (92%) of the 95 respondents were familiar with the Guide,
      and 80 respondents had used it. The 4 components used most frequently were the
      basic generalist competencies (used by 83% of those familiar with the Guide),
      learning objectives for these competencies (used by 83%), learning objectives for
      training problems (used by 70%), and specific training problems (used by 67%);
      74% to 85% of those using these components found them moderately or very useful.
      The most frequently identified barriers to use of the Guide were insufficient
      faculty time, insufficient number of ambulatory care preceptors and training
      sites, and need for more faculty development. About 30% or more of those familiar
      with the Guide reported that use of the Guide was associated with improved
      ability to meet clerkship accreditation criteria, improved performance of
      students on the clerkship exam, and increased clerkship time devoted to
      ambulatory care. CONCLUSION: This federally supported initiative that engaged the
      collaborative efforts of the SGIM and the CDIM was successful in facilitating
      significant changes in the medicine core clerkship across the United States.

PMID- 10940134
TI  - A physician survey of the effect of drug sample availability on physicians'
      behavior.
AB  - OBJECTIVE: Pharmaceutical companies often use drug samples as a marketing
      strategy in the ambulatory care setting. Little is known about how the
      availability of drug samples affects physicians' prescribing practices. Our goal
      was to assess: (1) under what circumstances and why physicians dispense drug
      samples, (2) if drug samples lead physicians to use medications other than their
      preferred drug choice, and (3) the physician characteristics that are associated
      with drug sample use. DESIGN: Cross-sectional survey. SETTING: University-based
      clinics at one academic medical center. PARTICIPANTS: 154 general medicine and
      family physicians. MEASUREMENTS AND MAIN RESULTS: Physicians' self-reported
      prescribing patterns for 3 clinical scenarios, including their preferred drug
      choice, whether they would use a drug sample and subsequently prescribe the
      sampled medication, and the importance of factors involved in the decision to
      dispense a drug sample. A total of 131 (85%) of 154 physicians responded. When
      presented with an insured woman with an uncomplicated lower urinary tract
      infection, 22 (17%) respondents reported that they would dispense a drug sample;
      21 (95%) of 22 sample users stated that they would dispense a drug sample that
      differed from their preferred drug choice. For an uninsured man with
      hypertension, 35 (27%) respondents reported that they would dispense a drug
      sample; 32 (91%) of 35 sample users indicated that they would dispense a drug
      sample instead of their preferred drug choice. For an uninsured woman with
      depression, 108 (82%) respondents reported that they would dispense a drug
      sample; 53 (49%) of 108 sample users indicated that they would dispense a drug
      sample that differed from their preferred drug choice. Avoiding cost to the
      patient was the most consistent motivator for dispensing a drug sample for all 3
      scenarios. For 2 scenarios, residents were more likely to report using drug
      samples than attendings (P <.05). When respondents who chose a drug sample for 2
      or 3 scenarios were compared to those who never chose to use a drug sample, or
      chose a drug sample for only one scenario, only younger age was independently
      associated with drug sample use. CONCLUSION: In self-reports, the availability of
      drug samples led physicians to dispense and subsequently prescribe drugs that
      differ from their preferred drug choice. Physicians most often report using drug
      samples to avoid cost to the patient.

PMID- 10940136
TI  - Patient participation in research in the managed care environment: key
      perceptions of members in an HMO.
AB  - This study's objective was to elicit the views of research among enrollees in an
      HMO. A questionnaire was mailed to 207 adult enrollees, 55% had been exposed to
      research and 45% had not. Ninety-four percent of respondents supported research
      within the HMO, and 87% thought using information from medical records for
      research was acceptable. Sixty-three percent thought participation in research
      increased patient understanding of health care. Significantly more prior research
      participants thought that participation in research improves care. More patients
      would participate if written information were provided (67%), if feedback of
      results was provided (72%), and if their clinician invited them (67%). Only a
      modest percentage (20%) of patients would participate in a randomized trial.

PMID- 10940137
TI  - Will German patients accept their family physician as a gatekeeper?
AB  - OBJECTIVE: Looking to the experience in the United States with managed care and
      the possible introduction of gatekeeping in the near future in Germany, we
      performed a population-based survey to examine preferences for future gatekeeping
      arrangements. DESIGN: Cross-sectional telephone survey. SETTING: Four health
      districts in Thuringia (formerly East Germany) and Lower Saxony (formerly West
      Germany). PARTICIPANTS: Out of a random sample of 644 adults in the 4 districts,
      415 persons (64.4%) took part in the survey. MEASUREMENTS AND MAIN RESULTS: Using
      multiple logistic regression, we analyzed associations between preferences for
      gatekeeping arrangements and patient satisfaction, insurance status, and
      sociodemographic characteristics. Seventy-four percent of respondents valued
      first-contact care, especially older people (odds ratio [OR], 4.3; 95% confidence
      interval [95% CI], 2.0 to 9.3), people who were very satisfied with the
      relationship with their family physician (OR, 2.7; 95% CI, 1.6 to 4.8) and
      members of sickness funds in contrast to privately insured persons (OR, 2.4; 95%
      CI, 1.2 to 5.2). The family physician's influence in coordinating the use of
      specialist services was appreciated by 86%, more often by members of sickness
      funds (OR, 5.9; 95% CI, 2.4 to 14. 3), people who were very satisfied with their
      doctor's professional competence (OR, 3.2; 95% CI, 1.6 to 6.3) and older persons
      (OR, 2.9; 95% CI, 1.1 to 7.7). CONCLUSIONS: A vast majority of the German
      population would accept their family physician as entry point and as coordinator
      of all other health services. Since patient satisfaction, among other reasons,
      strongly influenced preferences for gatekeeper arrangements, family physicians
      themselves may be able to promote primary care health services.

PMID- 10940138
TI  - Supporting the moral development of medical students.
AB  - Philosophers who studied moral development have found that individuals normally
      progress rapidly in early adulthood from a conventional stage in which they base
      behavior on the norms and values of those around them to a more principled stage
      where they identify and attempt to live by personal moral values. Available data
      suggest that many medical students, who should be in this transition, show little
      change in their moral development. Possibly, this relates to perceived pressures
      to conform to the informal culture of the medical wards. Many students experience
      considerable internal dissidence as they struggle to accommodate personal values
      related to empathy, care, and compassion to their clinical training. Educational
      interventions that positively influence this process have established regular
      opportunities for critical reflection by the students in small groups. Other
      interventions include faculty development to enhance role modeling and feedback
      by clinical faculty. The author espouses more widespread adoption of these
      educational interventions.

PMID- 10940139
TI  - Patients' trust in physicians: many theories, few measures, and little data.
AB  - Trust is one of the central features of patient-physician relationships. Rapid
      changes in the health care system are feared by many to be threatening patients'
      trust in their physicians. Yet, despite its acknowledged importance and potential
      fragility, rigorous efforts to conceptualize and measure patient trust have been
      relatively few. This article presents a synopsis of theories about patient trust
      and the evolution of methods to measure it. Clinicians, educators, and
      researchers interested in this area may find this information useful in practice
      and teaching. The gaps identified in our knowledge about trust can help target
      new efforts to strengthen the methodological basis of work to understand this
      vital element of medical relationships.

PMID- 10940141
TI  - Time, autonomy, and satisfaction.

PMID- 10940140
TI  - Should medical schools be schools for virtue?

PMID- 10940142
TI  - The world we live in: health policy from a primary care perspective.

PMID- 10940143
TI  - Treatment preferences among depressed primary care patients.
AB  - OBJECTIVE: To understand patient factors that may affect the probability of
      receiving appropriate depression treatment, we examined treatment preferences and
      their predictors among depressed primary care patients. DESIGN: Patient
      questionnaires and interviews. SETTING: Forty-six primary care clinics in 7
      geographic regions of the United States. PARTICIPANTS: One thousand one hundred
      eighty-seven English- and Spanish-speaking primary care patients with current
      depressive symptoms. MEASUREMENTS AND MAIN RESULTS: Depressive symptoms and
      diagnoses were determined by the Composite International Diagnostic Interview
      (CIDI) and the Center for Epidemiological Studies Depression Scale (CES-D).
      Treatment preferences and characteristics were assessed using a self-administered
      questionnaire and a telephone interview. Nine hundred eight-one (83%) patients
      desired treatment for depression. Those who preferred treatment were wealthier
      (odds ratio [OR], 3.7; 95% confidence interval [95% CI], 1.8 to 7.9; P =.001) and
      had greater knowledge about antidepressant medication ( OR, 2.6; 95% CI, 1.6 to
      4.4; P </=.001) than those who did not want treatment. A majority ( 67%, n = 660)
      of those preferring treatment preferred counseling, with African Americans (OR,
      2.2; 95% CI, 1.0 to 4.8, P =. 04 compared to whites) and those with greater
      knowledge about counseling (OR, 2.1; 95% CI, 1.6 to 2.7, P </=.001) more likely
      to choose counseling. Three hundred twelve ( 47%) of the 660 desiring counseling
      preferred group over individual counseling. Depression severity was only a
      predictor of preference among those already in treatment. CONCLUSIONS: Despite
      low rates of treatment for depression, most depressed primary care patients
      desire treatment, especially counseling. Preferences for depression treatment
      vary by ethnicity, gender, income, and knowledge about treatments.

PMID- 10940144
TI  - Postmenopausal estrogen therapy and depressive symptoms in older women.
AB  - BACKGROUND: Evidence regarding the effect of postmenopausal estrogen therapy on
      mood is limited. METHODS: To determine whether postmenopausal estrogen therapy is
      associated with fewer depressive symptoms in elderly women, we conducted a cross
      sectional study of 6, 602 white women ages 71 years or older who were recruited
      from population-based listings in Baltimore, Md; Minneapolis, Minn; Portland,
      Ore; and the Monongahela Valley, Pa. Use of estrogen and progestin was determined
      by interview. Participants completed the Geriatric Depression Scale short form
      (GDS) and were considered depressed if they reported 6 or more of 15 possible
      symptoms of depression. RESULTS: A total of 6.3% (72/1,150) of current estrogen
      users, 7.2% (142/1,964) of past estrogen users, and 9.0% (313/3,488) of never
      users reported 6 or more symptoms of depression (P =.004). Current estrogen users
      had a decreased risk of reporting 6 or more depressive symptoms, compared with
      not current (past or never) users of estrogen (odds ratio [OR], 0.7; 95% CI, 0.5
      to 0.9; P =.01], adjusted for living alone, bilateral oophorectomy, current
      smoking, physical activity, social network, self-perceived health, cognitive
      function, functional status, and antidepressant use. However, excluding women who
      use estrogen or progestin alone, we were unable to find an association between
      current use of combined estrogen plus progestin therapy and depressive symptoms
      (adjusted OR, 0.8; 95% CI, 0.5 to 1.4; P =.5). CONCLUSIONS: This cross-sectional
      study found that current use of unopposed estrogen was associated with a
      decreased risk of depressive symptoms in older women. Additional studies are
      needed to understand the effect of combined estrogen and progestin therapy on the
      prevalence of depressive symptoms in older women.

PMID- 10940145
TI  - Prevalence and duration of postmenopausal hormone replacement therapy use in a
      managed care organization, 1990-1995.
AB  - OBJECTIVE: To determine the prevalence and duration of postmenopausal hormone
      replacement therapy (HRT) use and identify correlates of adherence to therapy.
      DESIGN: Population-based cohort study. SETTING: Staff-model health maintenance
      organization. PARTICIPANTS: Female members, 40 years and older. MEASUREMENTS AND
      MAIN RESULTS: Prevalence and duration of use were measured between 1990 and 1995.
      Duration was assessed by Kaplan-Meier and proportional hazards methods. Hormone
      replacement therapy use increased from 10.3% in 1990 to 20.7% in 1995. Greatest
      use (24%) occurred among menopausal women age 50 to 54 years. Less than 5% of
      women 75 and older used HRT. Among 1,680 first-time recipients of HRT, two thirds
      of initial prescriptions were written by internists. Thirty-eight percent
      discontinued HRT within 1 year. For the subset whose indication for therapy was
      ascertained, prevention of chronic disease was associated with a 33% 1-year
      discontinuation rate. Factors associated with longer duration of therapy included
      white race (relative risk [RR], 1.63; 95% confidence interval [95% CI], 1.32 to
      2.02), younger age (RR, 1.02 per year; 95% CI 1.01 to 1.03), and changing the
      preparation or dose of estrogen (RR, 5.62; 95% CI, 4.33 to 7.25). The formulation
      (esterified estrogens 0.625 mg versus conjugated estrogens 0.625 mg) was also
      associated with greater duration of use; all other estrogens were, as a group,
      associated with shorter duration of use. Those who received their initial HRT
      prescription from an internist were more likely to continue therapy than those
      who received it from a gynecologist. CONCLUSIONS: Despite increased use of HRT,
      only a minority of women in this population used HRT, and many of those
      discontinued therapy within 1 year.

PMID- 10940146
TI  - Revisiting the oral glucose tolerance test criterion for the diagnosis of
      diabetes.
AB  - OBJECTIVE: The Expert Committee on the Diagnosis and Classification of Diabetes
      retained the 2-hour glucose concentration on an oral glucose tolerance test of
      >/=11.1 mmol/L (200 mg/dL) as a criterion to diagnose diabetes. Since glycated
      hemoglobin levels have emerged as the best measure of long-term glycemia and an
      important predictor of microvascular and neuropathic complications, we evaluated
      the distribution of hemoglobin A1C (Hb A1C) levels in individuals who had
      undergone an oral glucose tolerance test to determine how well 2-hour values
      could identify those with normal versus increased Hb A1C levels. DESIGN: A cross
      sectional analysis of 2 large data sets was performed. We cross-tabulated 2-hour
      glucose concentrations on an oral glucose tolerance test separated into 4
      intervals (<7.8 mmol/L [140 mg/dL], 7.8-11.0 mmol/L [140-199 mg/dL], 11.1-13.3
      mmol/L [200-239 mg/dL], and >/=13.3 mmol/L [240 mg/dL]) with Hb A1C levels
      separated into 3 intervals (normal; <1% above the upper limit of normal; and
      greater than or equal to the upper limit of normal + 1%). RESULTS: Approximately
      two thirds of patients in both data sets with 2-hour glucose concentrations of
      11.1 to 13.3 mmol/L (200-239 mg/dL) had normal Hb A1C levels. In contrast, 60% to
      80% of patients in both data sets with 2-hour glucose concentrations >/=13.3
      mmol/L (240 mg/dL) had elevated Hb A1C levels. CONCLUSION: Since Hb A1C levels
      are the best measures presently available that reflect long-term glycemia, we
      conclude that the 2-hour glucose concentration criterion on an oral glucose
      tolerance test for the diagnosis of diabetes should be raised from >/= 11.1
      mmol/L (200 mg/dL) to >/= 13.3 mmol/L (240 mg/dL) to remain faithful to the
      concept that diagnostic concentrations of glucose should predict the subsequent
      development of specific diabetic complications (e.g., retinopathy).

PMID- 10940147
TI  - Clinical work sampling A new approach to the problem of in-training evaluation.
AB  - OBJECTIVE: Existing systems of in-training evaluation (ITE) have been criticized
      as being unreliable and invalid methods for assessing student performance during
      clinical education. The purpose of this study was to assess the feasibility,
      reliability, and validity of a clinical work sampling (CWS) approach to ITE. This
      approach focused on the following: (1) basing performance data on observed
      behaviors, (2) using multiple observers and occasions, (3) recording data at the
      time of performance, and (4) allowing for a feasible system to receive feedback.
      PARTICIPANTS: Sixty-two third-year University of Ottawa students were assessed
      during their 8-week internal medicine inpatient experience. MEASUREMENTS AND MAIN
      RESULTS: Four performance rating forms (Admission Rating Form, Ward Rating Form,
      Multidisciplinary Team Rating Form, and Patient's Rating Form) were introduced to
      document student performance. Voluntary participation rates were variable (12%
      64%) with patients excluded from the analysis because of low response rate (12%).
      The mean number of evaluations per student per rotation (19) exceeded the number
      of evaluations needed to achieve sufficient reliability. Reliability coefficients
      were high for the Ward Form (.86) and the Admission Form (.73) but not for the
      Multidisciplinary Team (.22) Form. There was an examiner effect (rater leniency),
      but this was small relative to real differences between students. Correlations
      between the Ward Form and the Admission Form were high (.47), while those with
      the Multidisciplinary Team Form were lower (.37 and .26, respectively). The CWS
      approach ITE was considered to be content valid by expert judges. CONCLUSIONS:
      The collection of ongoing performance data was reasonably feasible, reliable, and
      valid.

PMID- 10940148
TI  - Physical abuse of urban Native Americans.
AB  - To ascertain the extent of, and risk factors for, physical abuse among older
      urban American Indian/Alaska Natives (AI/ANs), we conducted a chart review of 550
      urban AI/AN primary care patients >/=50 years old seen during 1 year.
      Mistreatment was documented in 10%. A logistic regression found younger age (P
      <.001), female gender (P <.001), current depression (P <.001), and dependence on
      others for food (P <.05) to be significant correlates of physical abuse. In only
      31% of instances of definite abuse were the authorities notified. We conclude
      that providers should be alert to the possibility of physical mistreatment among
      older urban AI/ANs. Improvements in detection and management are sorely needed.

PMID- 10940149
TI  - Sheltered versus nonsheltered homeless women differences in health, behavior,
      victimization, and utilization of care.
AB  - OBJECTIVE: To contrast sociodemographic characteristics, physical and mental
      health status, substance use, sexual behaviors, victimization, and utilization of
      health services between homeless women residing in sheltered and non-sheltered
      environments. DESIGN: Cross-sectional survey. A structured scale was used to
      measure mental health status. Physical health status, substance use, sexual
      behavior, history of adult victimization, and health services utilization were
      measured by content-specific items. SETTING: Shelters (N = 47) and outdoor
      locations in Los Angeles. PARTICIPANTS: One thousand fifty-one homeless women.
      RESULTS: Homeless women living on the streets were more likely than sheltered
      women to be white and longer-term homeless. Controlling for sociodemographic
      characteristics, multiple logistic regression analyses revealed that unsheltered
      women had over 3 times greater odds of fair or poor physical health, and over 12
      times greater odds of poor mental health than sheltered homeless women. They were
      also more likely than sheltered women to report using alcohol or noninjection
      drugs, to have multiple sexual partners, and to have a history of physical
      assault. About half of the overall sample reported utilization of a variety of
      health services; however, unsheltered homeless women were less likely to utilize
      all of the health services that were assessed, including drug treatment.
      CONCLUSIONS: There is a critical need for aggressive outreach programs that
      provide mental health services and substance abuse treatment for homeless women
      on the streets. Comprehensive services that also include medical care, family
      planning, violence prevention, and behavioral risk reduction may be particularly
      valuable for homeless women, especially those living in unsheltered environments.

PMID- 10940150
TI  - Chaperone use by residents during pelvic, breast, testicular, and rectal exams.
AB  - We designed a questionnaire survey to study internal medicine residents' plans to
      use a chaperone during the pelvic, breast, rectal, and testicular examinations.
      We found chaperone use by male and female residents differed markedly, and
      neither group planned to use chaperones universally. When examining female
      patients, male residents overall were very likely to use a chaperone during a
      pelvic exam, but less likely for the breast exam and rectal exam. For the female
      resident, there was a significantly lower likelihood of using chaperones during
      the pelvic, breast, or rectal exams. There was a much lower rate of chaperone use
      during the sensitive portions of the male physical examination compared with the
      female examination, with somewhat higher use by female residents. We concluded
      that male and female residents differ significantly in their patterns of
      chaperone use. It would be valuable to develop guidelines for chaperone use to
      help residents understand the issues involved in the choices, and to protect the
      residents from the possible medico-legal consequences of forgoing chaperones.

PMID- 10940153
TI  - Women's health. An evolving mosaic.

PMID- 10940152
TI  - Problems in recruiting community-based physicians for health services research.
AB  - OBJECTIVE: To qualitatively determine factors that are associated with higher
      participation rates in community-based health services research requiring
      significant physician participation burden. MEASUREMENTS: A review of the
      literature was undertaken using MEDLINE and the Social Science Research Index to
      identify health services research studies that recruited large community-based
      samples of individual physicians and in which the participation burden exceeded
      that of merely completing a survey. Two reviewers abstracted data on the
      recruitment methods, and first authors were contacted to supplement published
      information. MAIN RESULTS: Sixteen studies were identified with participation
      rates from 2.5% to 91%. Almost all studies used physician recruiters to
      personally contact potential participants. Recruiters often knew some of the
      physicians to be recruited, and personal contact with these "known" physicians
      resulted in greater participation rates. Incentives were generally absent or
      modest, and at modest levels, did not appear to affect participation rates.
      Investigators were almost always affiliated with academic institutions, but were
      divided as to whether this helped or hindered recruitment. HMO-based and minority
      physicians were more difficult to recruit. Potential participants most often
      cited time pressures on staff and themselves as the study burden that caused them
      to decline. CONCLUSIONS: Physician personal contact and friendship networks are
      powerful tools for recruitment. Participation rates might improve by including
      HMO and minority physicians in the recruitment process. Investigators should
      transfer as much of the study burden from participating physicians to project
      staff as possible.

PMID- 10940151
TI  - Detection, evaluation, and treatment of eating disorders the role of the primary
      care physician.
AB  - OBJECTIVE: To describe how primary care clinicians can detect an eating disorder
      and identify and manage the associated medical complications. DESIGN: A review of
      literature from 1994 to 1999 identified by a MEDLINE search on epidemiology,
      diagnosis, and therapy of eating disorders, including anorexia nervosa and
      bulimia nervosa. MEASUREMENTS AND MAIN RESULTS: Detection requires awareness of
      risk factors for, and symptoms and signs of, anorexia nervosa (e.g.,
      participation in activities valuing thinness, family history of an eating
      disorder, amenorrhea, lanugo hair) and bulimia nervosa (e.g., unsuccessful
      attempts at weight loss, history of childhood sexual abuse, family history of
      depression, erosion of tooth enamel from vomiting, partoid gland swelling, and
      gastroesophageal reflux). Providers must also remain alert for disordered eating
      in female athletes (the female athlete triad) and disordered eating in diabetics.
      Treatment requires a multidisciplinary team including a primary care
      practitioner, nutritionist, and mental health professional. The role of the
      primary care practitioner is to help determine the need for hospitalization and
      to manage medical complications (e.g., arrhythmias, refeeding syndrome,
      osteoporosis, and electrolyte abnormalities such as hypokalemia). CONCLUSION:
      Primary care providers have an important role in detecting and managing eating
      disorders.

PMID- 10940154
TI  - Diagnosing diabetes. A practitioner's plea: keep it simple.

PMID- 10940155
TI  - How are we doing? The problem of in-training evaluation.

PMID- 10940156
TI  - Infection and preterm birth: evidence of a common causal relationship with
      bronchopulmonary dysplasia and cerebral palsy.
AB  - Subclinical genital tract infection has been clearly established as a significant
      cause of spontaneous preterm birth, particularly in early gestations. Bacterial
      vaginosis organisms rank highly among the pathogens involved in preterm labour
      and there is considerable beneficial evidence from the use of prophylactic
      antibiotics for women at high risk of preterm birth. The pathogenesis involves
      activation of macrophages and the generation of pro-inflammatory cytokines.
      Bronchopulmonary dysplasia is seen in the most immature of survivors and appears
      to be secondary to interruption of normal development and maturation of the
      lungs. The link between chorioamnionitis and lung injury in utero and subsequent
      development of bronchopulmonary dysplasia has now been substantiated. Exposure to
      pro-inflammatory cytokines is implicated in the impairment of the fetal lung. A
      significant body of evidence supports the association between chorioamnionitis,
      periventricular leukomalacia and cerebral palsy. Biological mechanisms that
      explain the association between chorioamnionitis and fetal brain injury involve
      pro-inflammatory cytokines. Similarity in the pattern of expression of cytokines
      suggests a common pathway for the initiation of preterm labour and also injury to
      the lung and the central nervous system of the fetus.

PMID- 10940157
TI  - Persistent crying in infancy: a persistent clinical conundrum.

PMID- 10940158
TI  - Consultant paediatric workforce in Australia: numbers and needs.

PMID- 10940159
TI  - Medicalizing normality? Management of irritability in babies.
AB  - OBJECTIVE: The aims of this project were to identify the scources and quality of
      the health advice provided to parents with irritable infants; to assess the
      efficacy of a residential programme in the diagnosis and management of irritable
      infants; and to assess the intermediate term outcome for such infants and their
      mothers. METHODOLOGY: All mother-infant pairs admitted during a 3 month period to
      a residential setting with the primary concern of infant irritability were asked
      to participate in the study. Pre-admission and 3 month post-discharge health-care
      advice, investigations and treatment details were collected. Maternal mood at
      admission and 3 months post-discharge was measured using the Edinburgh Postnatal
      Depression Scale (EPDS). On admission, infant medication for proposed cause of
      excess irritability was ceased, with parental consent, if it was appropriate and
      following full medical assessment. Individual case plans were designed by the
      admitting child health nurse in consultation with the mother. These included
      education as to normal infant behaviour, settling techniques, and establishment
      of routine; family issues were also explored. RESULTS: Fifty-one consecutive
      mother-infant pairs consented to participate and formed the cohort, 48 (94%) were
      available for follow-up interview 3 months post-discharge. The average age on
      admission was 13 weeks (range 4-28 weeks), 32 (62.7%) were male, 34 (66.7%) were
      first born and 45 (88.2%) lived with both their parents. A multiplicity of health
      professionals had been involved in the pre-admission care, and 48 of the infants
      had been or were currently on medication for gastro-oesophageal reflux disease
      and or colic. At the end of admission, diagnoses made were predominantly
      behavioural (22) and feeding problems (20). Nine infants were felt to have an
      organic cause for their irritability. Maternal mood improved significantly on
      EPDS from the time of admission (45 (86.2%) of mothers with scores > or = 12,
      mean score 16.5) to post-admission follow up (9 (18. 8%) with scores > or = 12,
      mean score 7.2). CONCLUSIONS: There is evidence that a proportion of babies with
      'normal' irritability are being incorrectly diagnosed as having an organic
      disorder exposing them inappropriately to medication, which may be harmful, and
      potentially creating lifelong problems for these infants and their families.

PMID- 10940160
TI  - Trends in the specialist workforce in paediatrics in Australia, 1981-1997.
AB  - OBJECTIVE: The Royal Australasian College of Physicians has conducted periodic
      workforce censuses of Fellows practising paediatric medicine in Australia since
      1981. The aim of this study was to document trends in the supply of
      paediatricians and to project these trends into the early 21st century.
      METHODOLOGY: Time series analysis using least squares regression. RESULTS: The
      paediatric consultant workforce in Australia increased in a linear manner from
      374 in 1981 to 777 in 1997. If this trend persists, the number of paediatricians
      will grow by 62% to 1255 in 2016. The ratio of population aged 0-14 years per
      paediatrician fell from 9960:1 in 1981 to 5040:1 in 1997. The projected national
      decline in the child population will result in a ratio of 3050 children per
      paediatrician in the year 2016. The proportion of women in the paediatric
      workforce was 22.4% in 1997 and is projected to rise to at least 36% by 2016. The
      proportion aged 50 years and older rose from 22% in 1981 to 33.6% in 1997 and is
      projected to be 45% by the year 2016. The average total weekly working hours fell
      from 58.2 in 1984 to 53. 4 in 1997. The proportion practising in regional centres
      rose from 12 to 17.9%. CONCLUSIONS: The paediatric workforce in Australia has
      grown rapidly over the past 16 years. If this trend continues, the ratio of child
      population per paediatrician will continue to fall, acccentuated by the projected
      decline in the child population. The trends towards an ageing workforce with an
      increasing proportion of women, declining working hours and rising proportion
      practising in regional centres are expected to continue unless workforce intake
      or retirement change dramatically.

PMID- 10940161
TI  - Impact of infant feeding practices on the risk of mother to child transmission of
      HIV-1 in Zimbabwe.
AB  - OBJECTIVE: To determine the magnitude of the contribution of infant feeding
      practices on the risk of mother to child transmission (MTCT) of the HIV-1
      infection. METHODOLOGY: Prospective data from birth until 24 months of age on 236
      infants born to HIV-positive mothers in Harare, Zimbabwe was analysed for this
      study. However, because only a small proportion of infants (2.1%) were HIV-1
      polymerase chain reaction (PCR) tested shortly after birth, the PCR results for
      infants at birth were not incorporated into our analyses. The contribution of
      infant feeding practices on the risk of MTCT of HIV-1 was assessed using Cox
      Proportional Hazards Regression Models. RESULTS: The incidence of HIV-1 through
      MTCT was greatest among breastfed (8.33 per 100 child-months) and mixed fed (8.64
      per 100 child-months) infants by 3 months. After adjustment for maternal age,
      marital status, education and infant antibody HIV-1 status, the cumulative
      relative risk of MTCT of HIV-1 was 4.19 (95% confidence interval (CI) 3.44, 5.09)
      among breastfed and 1.10 (95% CI 0.97, 1. 25) among mixed fed infants. The
      overall MTCT rate of HIV-1 in this study was 40.3%. CONCLUSIONS: Breastfed
      infants had the greatest cumulative relative risk of MTCT of HIV-1, followed by
      mixed fed infants, with the highest incidences occurring within the first 3
      months.

PMID- 10940162
TI  - Critical influenza virus infection.
AB  - OBJECTIVE: To determine the risk of death from influenza infection in children
      with chronic underlying disease. METHODOLOGY: An 18-year retrospective study of
      children with 'critical' influenza A or B virus infection, defined as requiring
      admission to intensive care or resulting in death, but excluding
      laryngotracheobronchitis (LTB). Influenza infection was diagnosed by viral
      culture and/or immunofluorescence of respiratory secretions. Patients with LTB
      were analysed separately. RESULTS: There were 27 cases of critical influenza
      virus infection over the study period, comprising 26 admissions to the intensive
      care unit (excluding LTB) and one death on the general wards. Thirteen (48%) of
      the 27 children had chronic underlying disease. In addition, 12 children with LTB
      were admitted to the intensive care unit. The LTB children were older and less
      likely to have chronic underlying disease. Nosocomial infection caused seven
      (26%) of the 27 critical infections. Nine (33%) of the 27 children with critical
      influenza died. Six (46%) of 13 children with chronic underlying disease and
      influenza admitted to intensive care died, compared with three of 14 (21%)
      without any underlying disease (odds ratio = 3.1, 95% confidence interval 0.6
      14.0). CONCLUSIONS: Critical life-threatening influenza virus infection was
      uncommon, but the mortality was high (33%), particularly in children with chronic
      underlying disease. Nosocomial infection with influenza was an important cause of
      admission to intensive care.

PMID- 10940163
TI  - Rib fractures in infants: red alert! The clinical features, investigations and
      child protection outcomes.
AB  - OBJECTIVE: To examine clinical features, investigation methods and outcomes of
      infants with rib fractures. METHODOLOGY: All infants aged 2 years or younger who
      presented over a 5-year period with documented rib fractures were identified from
      the medical records database of a tertiary referral paediatric hospital and data
      collected by retrospective chart review. Additional data regarding notifications
      and placements were obtained from the Department of Families Youth and Community
      Care, Queensland. RESULTS: Rib fractures were attributed to child abuse in 15 of
      18 infants identified. The initial presentation in the abused infants was most
      often as a result of intracranial pathology and limb fractures. In four cases the
      rib fractures were incidental findings when abuse had not been suspected. Bone
      scintigraphy revealed eight previously undetected rib injuries in four cases. In
      three cases of abuse, the rib fractures were an isolated finding. Three of the
      infants with inflicted rib injuries were discharged home. In one such infant a
      significant re-injury occurred. Three returned home with implicated adults no
      longer in residence, and nine spent a mean period of 12 months in foster care.
      CONCLUSIONS: Rib fractures in infancy are usually caused by severe physical
      abuse. Accidental rib fractures are rare in infants and result from massive
      trauma. Rib fractures, multiple or single, may occur in isolation in abused
      infants. The implications of such injuries must be recognized to ensure
      appropriate, safe and consistent child protection outcomes. Bone scintigraphy is
      more sensitive than radiographs in the detection of acute rib fractures and
      should be performed in all cases of suspected infant abuse.

PMID- 10940164
TI  - Plasminogen activator inhibitor type-1 and interleukin-6 in haemolytic uraemic
      syndrome.
AB  - OBJECTIVE: Because haemolytic uraemic syndrome (HUS) is an important cause of
      renal dysfunction in children, the availability of prognostic markers of disease
      severity could assist in identifying those at risk of developing long-term
      sequelae. The aim of this study was to test the hypothesis that plasma levels of
      plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in
      children at the time of diagnosis of HUS would predict renal function outcome in
      terms of glomerular filtration rate (GFR). METHODOLOGY: Fourteen children
      suffering from diarrhoeal HUS were studied. Plasma samples were assayed for PAI-1
      and IL-6, and GFR was measured at intervals after discharge from hospital. Twelve
      months following their recovery from HUS, the children were allocated to one of
      two outcome groups depending on whether GFR was above (Good Outcome, n = 9), or
      below (Poor Outcome, n = 5) 80 mL/min per 1.73 m2. RESULTS: Elevated
      concentrations of PAI-1 were found in 4 of 5 Poor Outcome and 4 of 9 Good Outcome
      children. At the same time, increased concentrations of IL-6 were observed in 3
      of 5 Poor Outcome and 3 of 9 Good Outcome children. Renal function continued to
      be compromised in four Poor Outcome children 36 months after diagnosis.
      CONCLUSIONS: Our data show that PAI-1 and IL-6 are elevated in the plasma of some
      children at the time of diagnosis of HUS, but that neither is a definitive
      prognostic marker of poor outcome 3 years later.

PMID- 10940165
TI  - Comparison of influenza A and influenza B virus infection in hospitalized
      children.
AB  - BACKGROUND: Influenza A and B viruses were cocirculating in Australia in the
      winter of 1997. OBJECTIVE: To compare the clinical and demographic features of
      children with influenza A or influenza B virus infection admitted to a paediatric
      tertiary referral centre. METHODOLOGY: Retrospective chart review of 91
      hospitalized children with culture-proven influenza A or B virus infection during
      1997. RESULTS: Thirty-six (56%) of 64 children with influenza A were under 12
      months of age compared with seven (26%) of 27 children with influenza B virus
      infection (P = 0.02). Influenza B virus infection was more common in children
      with underlying medical problems (P = 0. 01). Neurological manifestations were
      present in eight (12.5%) of 64 children with influenza A and none with influenza
      B virus infection (P = 0.09). There were no significant differences in signs and
      symptoms of children with influenza A and B virus infection, in severity of
      illness or in duration of hospital stay. CONCLUSIONS: A greater proportion of
      children admitted with influenza A virus infection were under 12 months of age.
      Influenza B virus infection is associated more commonly with underlying medical
      disorders. It is not possible to differentiate between influenza A or B virus
      infection from presenting clinical signs and symptoms.

PMID- 10940166
TI  - Family data in Rett syndrome: association with other genetic disorders.
AB  - BACKGROUND: Rett syndrome is a neurological disorder, almost exclusively
      affecting girls. METHODOLOGY: Between 1993 and 1995 pedigree data were obtained
      from families of girls registered with the Australian Rett syndrome database.
      RESULTS: Although 21 individual disorders were reported to be present in family
      members of affected girls, there was no apparent clustering of the same disorder
      in different families. However it was certain that a geneticist had been involved
      in only 10.9% of cases. CONCLUSIONS: Mutations in the MECP2 gene have now been
      reported in a proportion of sporadic cases. Thus, it will be important to examine
      this phenotype-genotype correlation in the Australian cohort. Where a mutation is
      found, prenatal diagnosis in a subsequent pregnancy will be a possibility. Using
      the Australian population database and in conjunction with the clinical genetic
      services in each state it is planned to contact families with an affected girl to
      offer testing and counselling.

PMID- 10940167
TI  - Analysis of the breath hydrogen test for carbohydrate malabsorption: validation
      of a pocket-sized breath test analyser.
AB  - OBJECTIVE: To assess the validity and clinical application of a hand-held breath
      hydrogen (H2) analyzer (BreatH2, Europa Scientific, Crewe, UK). METHODOLOGY:
      Breath samples of patients referred to the Gastroenterology Unit, Women's and
      Children's Hospital, North Adelaide, South Australia, for confirmation of the
      diagnosis of carbohydrate malabsorption were analysed with the Quintron
      microlyzer (Quintron Instrument Co., Milwaukee, USA) and the BreatH2 analyser,
      using the Quintron microlyzer as the gold standard. RESULTS: Twenty-nine breath
      H2 tests (BHT) were performed in 29 patients aged 2 months to 61 years. The
      sensitivity and specificity of the BreatH2 analyser in detecting a positive BHT
      using the Quintron microlyser as the gold standard were 0.90 and 0.95 with
      positive and negative predictive values of 0.90 and 0.95, respectively. There was
      one false positive and one false negative reading. Bland-Altman plots showed a
      high degree of agreement between the values obtained with two different methods.
      CONCLUSIONS: The diagnosis of carbohydrate malabsorption, using a portable breath
      H2 analyser (BreatH2), achieved an acceptable degree of sensitivity and
      specificity, enabling it to be used where no alternative is available.

PMID- 10940169
TI  - Prevalence and pattern of childhood abdominal pain in an Australian general
      practice.
AB  - OBJECTIVE: Abdominal pain is a common problem in childhood and accounts for a
      significant workload in general practice. The aim of this study was assess the
      nature of abdominal pain in a sample of Australian children attending a Western
      Australian general practice for any reason, and to determine factors associated
      with the reporting of such pain. METHODOLOGY: A prospective study of children and
      their families attending a rural general practice was undertaken using a parental
      survey to assess the frequency and nature of abdominal pain, demographic
      features, physical and behavioural characteristics. RESULTS: Abdominal pain was
      common in this population; 44% (70 of 164) of parents reported that the index
      child had experienced abdominal pain in the past 12 months. The average age of
      children who experienced recent abdominal pain was 9 years and 9 months.
      Multivariate analysis suggested that children experiencing abdominal pain in the
      preceding 12 months were more likely to be anxious (odds ratio (OR) = 3.74, P =
      0.01), to have a family history of similar problems in siblings (OR = 4.26, P =
      0.01) and to experience sleep disturbance (OR = 3.90, P = 0.02) than children
      without abdominal pain. Consumption of three or more serves of wholemeal bread or
      cereals per day had a significant protective effect on reported abdominal pain in
      children (OR = 0.12, P = 0.03). The majority of families (66%) dealt with the
      pain without resorting to medical care. CONCLUSIONS: Abdominal pain remains a
      common problem of children attending an Australian general practice, and was
      associated with features suggesting that it is related to anxiety and coping
      ability. Abdominal pain is not usually associated with disease; most families
      recognize this and cope with abdominal pain without medical consultation.

PMID- 10940168
TI  - Determining the best method for first-line assessment of neonatal blood glucose
      levels.
AB  - OBJECTIVE: To evaluate and compare the accuracy and performance of two
      electrochemical glucose meters. To determine the user acceptability of these
      glucose meters and the ABL 620 Blood Gas Analyser (Radiometer, Copenhagen,
      Denmark) with an electrochemical glucose oxidase electrode for use in a Level 2
      special care baby unit. METHODOLOGY: A total of 108 blood samples were collected
      from 47 babies at risk for hypoglycaemia. The blood glucose level was measured
      with two glucose meters, the Advantage Glucose Meter (Roche Diagnostics, Castle
      Hill, Australia) and the Precision-G Blood Glucose Testing System (Medisense,
      Melbourne, Australia), and the true blood glucose (TBG) measured with the ABL 620
      blood gas analyser. Results from the glucose meters were compared with the TBG
      (as a percentage of the TBG). RESULTS: The mean (SD) percentage difference
      between the Advantage Glucose Meter and TBG was 4.5% (12. 5), and Precision-G
      Glucose Meter and TBG was 15.4% (12.4). The sample haematocrit did not
      significantly influence the glucose meter/TBG differences. There was an overall
      preference by the nursing staff for the Advantage Glucose Meter. CONCLUSIONS: The
      Advantage Glucose Meter was significantly more accurate than the Precision-G with
      similar precision. It was the preferred method of screening for neonatal
      hypoglycaemia.

PMID- 10940170
TI  - Neonatal hypoglycaemia in infants of diabetic mothers.
AB  - OBJECTIVE: To determine whether umbilical cord blood glucose correlates with
      subsequent hypoglycaemia after birth in infants of well-controlled diabetic
      mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic
      mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33
      gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal
      blood glucose was maintained between 4 and 8 mmol/L during labour and delivery.
      Infants' plasma glucose levels were measured from venous cord blood and serially,
      at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood
      glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS:
      Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2
      mmol/L) during the first 2 h of life. There was no difference in the cord blood
      glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5
      +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior
      to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10
      vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly
      higher birthweight, and were more likely to be born to Caucasian mothers and by
      Caesarean section. Raised maternal fructosamine blood level, the need for insulin
      treatment or the infant's haematocrit were not different between infants with or
      without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the
      incidence of early hypoglycaemia in infants is still high, particularly in those
      mothers who had a longer duration of diabetes. Cord blood glucose level did not
      identify the infants with hypoglycaemia.

PMID- 10940171
TI  - Attitudes of neonatal clinicians towards resuscitation of the extremely premature
      infant: an exploratory survey.
AB  - OBJECTIVE: This study aims to explore the current attitudes of Australian
      neonatologists and nurses towards the resuscitation of extremely preterm infants.
      METHODOLOGY: An anonymous questionnaire regarding resuscitation of infants of
      less than 28 weeks gestation was sent to all neonatologists and three registered
      nurses in each perinatal centre in Australia. RESULTS: One hundred and thirty
      three questionnaires were sent. A return rate of 93% and 73% was obtained from
      neonatologists and nurses, respectively. Twenty-two per cent of neonatologists
      would 'occasionally' resuscitate at 22 weeks while none of the nurses would. A
      considerable proportion of neonatologists (23%) but only a few nurses (6%) would
      'quite often' resuscitate 23-week infants. The majority of neonatologists (85%)
      and nurses (88%) would 'almost always' resuscitate 24 week infants. More than
      half of the respondents would 'occasionally' resuscitate a 400-499 g infant and
      most would resuscitate infants weighing more than 500 g. Clinicians were not as
      optimistic of long-term outcome as they were for survival. Typically, only 52% of
      neonatologists and 38% of nurses thought babies of 25 weeks gestation had a
      greater than 50% chance of survival without major handicap. Parental wishes and
      the presence of congenital abnormalities were major influences on decision to
      resuscitate. Hypothetically, most respondents, more doctors than nurses, would
      consider initiating resuscitation without parental consent at a median gestation
      of 25 weeks. CONCLUSIONS: The majority of Australian clinicians would resuscitate
      at a gestation of 24 weeks or greater or at a birth weight of over 500 g despite
      conservative estimates of intact survival. This survey has brought to light the
      importance of communication with parents prior to extreme premature birth.

PMID- 10940172
TI  - Early cranial ultrasound changes as predictors of outcome during first year of
      life in term infants with perinatal asphyxia.
AB  - OBJECTIVES: To identify the types of early cranial ultrasound changes that were
      significant predictors of adverse outcome during the first year of life in
      asphyxiated term infants. METHODOLOGY: This was a prospective cohort study.
      Shortly after birth, cranial ultrasonography was carried out via the anterior
      fontanelles of 70 normal control infants and 104 asphyxiated infants with a
      history of fetal distress and Apgar scores of less than 6 at 1 and 5 min of life,
      or requiring endotracheal intubation and manual intermittent positive pressure
      ventilation for at least 5 min after birth. Neurodevelopmental assessment was
      carried out on the survivors at 1 year of age. RESULTS: Abnormal cranial
      ultrasound changes were detected in a significantly higher proportion (79.8%, or
      n = 83) of asphyxiated infants than controls (39.5%, or n = 30) (P < 0.0001).
      However, logistic regression analysis showed that only three factors were
      significantly associated with adverse outcome at 1 year of life among the
      asphyxiated infants. These were: (i) decreasing birthweight (for every additional
      gram of increase in birthweight, adjusted odds ratio (OR) = 0.999, 95% confidence
      interval (CI) 0.998, 1.000; P = 0.047); (ii) a history of receiving ventilatory
      support during the neonatal period (adjusted OR = 8.3; 95%CI 2.4, 28.9; P =
      0.0009); and (iii) hypoxic-ischaemic encephalopathy stage 2 or 3 (adjusted OR =
      5.8; 95%CI 1.8, 18.6; P = 0.003). None of the early cranial ultrasound changes
      was a significant predictor. CONCLUSIONS: Early cranial ultrasound findings,
      although common in asphyxiated infants, were not significant predictors of
      adverse outcome during the first year of life in asphyxiated term infants.

PMID- 10940173
TI  - Indicators of selenium status in Australian infants.
AB  - OBJECTIVE: To provide the first Australian data for the commonly used indicators
      of selenium (Se) status including plasma and erythrocyte Se and erythrocyte
      glutathione peroxidase (GSHPx) activity in newborn term and preterm infants from
      Adelaide, South Australia. Plasma Se levels from adults from Adelaide and
      Tasmania are also reported. METHODOLOGY: Descriptive, cross-sectional study of
      the indicators of Se status of newborn Australian preterm and term infants.
      RESULTS: Mean (+/- SD) plasma Se concentrations in the first 5 days of life for
      term (n = 48) and preterm (n = 90) infants were similar at 33 +/- 11 and 29 +/-
      14 microg/L, respectively. Glutathione peroxidase activity was lower in preterm
      than term infants (P < 0.001). Erythrocyte Se was lower in male (n = 74) compared
      with female (n = 57) infants (491 +/- 98 vs 561 +/- 134 ng/g Hb; P < 0.001).
      Adelaide adult plasma Se levels were 88 +/- 20 microg/L and higher than those of
      adult Tasmanian blood donors (77 +/- 13 microg/l, P < 0.05). CONCLUSIONS: These
      data indicate that values for indicators of Se status of Australian infants and
      adults are at the lower end of the international range. This article highlights
      the paucity of Australian data on the Se content in the food supply and the Se
      status of the Australian population. Given the increasing range and complexity of
      the biological roles of Se and the emerging evidence that Se may have important
      roles in prevention of cancer and other disorders, further data are required to
      clarify the Se status of Australians.

PMID- 10940174
TI  - Treatment of pleural empyema.
AB  - OBJECTIVE: To determine the clinical presentation and treatment strategies for
      children admitted with pleural empyema. METHODOLOGY: Retrospective review of
      medical and radiological records of 54 patients admitted with pleural empyema
      between January 1989 and April 1997. RESULTS: Fever (98%), cough (83%), chest
      pain (38%), clinical cyanosis (17%) and abdominal pain (16%) were common clinical
      features. The causative organism was identified in 17 patients (31%). Intravenous
      antibiotics were given for a mean of 18. 2 +/- 7.5 days. Forty-seven (87%)
      patients had closed chest tube drainage and 21(39%) patients underwent
      decortication for unsatisfactory response to medical treatment. The chest tube
      insertion was more likely to be delayed in patients who required decortication,
      although the difference was not significant (8.1 +/- 5.4 vs 6.3 +/- 5.2 days of
      illness, P = 0.67). All patients were discharged well, with almost complete
      resolution of the chest radiograph at 6 months. CONCLUSIONS: Intensive medical
      management with adequate chest tube drainage and appropriate antibiotics will
      result in full resolution for most patients. Surgical intervention is important
      in patients who fail to receive adequate treatment early in the disease.

PMID- 10940175
TI  - A randomized controlled trial of azithromycin and amoxycillin/clavulanate in the
      management of subacute childhood rhinosinusitis.
AB  - OBJECTIVE: Subacute childhood rhinosinusitis is a disorder commonly seen in
      children with allergic rhinitis. Antibiotics have been recommended as a major
      component of the treatment regime. The objective of the present study was to
      compare the effectiveness of a 3-day course of azithromycin and a 2-week course
      of amoxycillin/clavulanate in the treatment of subacute childhood rhinosinusitis.
      METHODOLOGY: A randomized single-blinded control study of subacute rhinosinusitis
      was conducted, comparing a 3-day course of azithromycin and a 2-week course of
      amoxycillin/clavulanate. Inclusion criteria were children aged between 5 and 16
      years, duration of nasal blockage or discharge between 30 and 120 days, and
      abnormal sinus radiographs. All enrolled children were prescribed budesonide
      nasal spray (Rhinocort Aqua Nasal Spray, Astra Pharmaceuticals, Sodertalje,
      Sweden) as adjuvant treatment. RESULTS: Forty-two children were recruited into
      the study and one defaulted on follow-up. Failure occurred in 6 of 20 for the
      azithromycin group and 5 of 21 for the amoxycillin/clavulanate group. The odds
      ratio was 1.46 (95%CI 0.37-5. 80, P = 0.73). No relapse occurred in azithromycin
      group and 5 of 21 in amoxycillin/clavulanate group. The odds ratio was 0.16
      (95%CI 0. 017-1.51, P = 0.18). Both antibiotics were well tolerated, however, two
      children, one from each group, complained of mild transient epigastric
      discomfort. CONCLUSIONS: This small study did not provide evidence of a
      difference between 14 days of amoxycillin/clavulanate and 3 days of azithromycin.
      Larger studies will be needed to determine which, if any, antibiotic regimen
      should be used in treating subacute childhood rhinosinusitis.

PMID- 10940176
TI  - Prevalence of tuberculosis infection among homeless young people in central and
      eastern Sydney.
AB  - OBJECTIVE: To determine the prevalence of tuberculosis (TB) infection among
      homeless young people (aged 12-25 years) in central and eastern Sydney.
      METHODOLOGY: A cross-sectional survey was conducted in 16 youth refuges and four
      drop-in centres in Central and Eastern Sydney Health Areas and at the Cellblock
      Youth Health Centre, Glebe and the Kirketon Road Centre, Darlinghurst, New South
      Wales (NSW). Participants completed a questionnaire and underwent Mantoux
      testing. RESULTS: One hundred and forty-one young people completed questionnaires
      and 139 received a Mantoux test; 112 (80. 6%) had their Mantoux read and 10
      (8.9%) were Mantoux positive (95% confidence interval 3.6-14.2). None of the risk
      factors examined were found to be associated with increased risk for TB
      infection. CONCLUSIONS: In this sample of homeless young people in central and
      eastern Sydney, the Mantoux positivity rate appears to be higher than the general
      population in NSW, but they would not currently be considered a high-risk group
      for TB infection.

PMID- 10940177
TI  - Hepatitis C infection in children: a Melbourne perspective.
AB  - OBJECTIVE: To examine the clinical spectrum of hepatitis C virus (HCV) infected
      children in our care by determining presentation, mode of acquisition, degree of
      co-infection, biochemical evidence of persisting hepatitis and treatment outcome.
      METHODOLOGY: A retrospective review of the medical records of all children
      attending the Royal Children's Hospital, Melbourne, between 1990 and 1998, who
      had antibodies to HCV infection detected. Detailed clinical information,
      investigations and the results of treatment were extracted from the clinical
      notes. RESULTS: A total of 94 children (age range 2 weeks to 19.7 years) were
      identified, of whom nine had passive transfer of maternal antibodies from HCV
      positive mothers and were excluded from analysis. Sixty-seven children (79%) were
      infected by transfusion of blood or blood products. Perinatal transmission
      occurred in 11 children (13%), and six children (7%) had a history of i.v. drug
      abuse. The majority of children were asymptomatic at presentation. Of the 65
      patients tested for HCV-ribonucleic acid, 43 (66%) were positive. Fifty-seven
      cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28
      months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co-infected
      with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four
      responded with normalisation of ALT from 3 to 12 months post-commencement of
      therapy. CONCLUSIONS: Although HCV was largely an asymptomatic condition in our
      clinic population, more than half the patients had biochemical evidence of
      ongoing liver damage. Given the chronicity of this infection in the majority of
      patients and the long-term risks of cirrhosis and hepatocellular carcinoma,
      children with HCV infection represent a high-risk group worthy of regular follow
      up.

PMID- 10940178
TI  - Athetoid quadriplegia and literacy.
AB  - OBJECTIVE: To compare literacy levels in athetoid quadriplegic (AQ) patients born
      in the 1960s and 1970s with those born in the 1980s and 1990s. METHODOLOGY: Nine
      patients with AQ born between 1966 and 1972 were compared with eight patients
      born between 1983 and 1991. RESULTS: Reading difficulties were found in almost
      all patients with AQ, despite normal intellect. Those in the earlier period were
      for the most part functionally literate, while those in the later period were
      functionally illiterate. CONCLUSIONS: Specific and intensive reading education
      may be required in patients with AQ to obtain functional literacy.

PMID- 10940179
TI  - Intussusception presenting as profound lethargy.

PMID- 10940180
TI  - Ethics forum: hydration in a dying patient.

PMID- 10940181
TI  - Clinical rhabdomyolysis.
AB  - Although rhabdomyolysis is an uncommon disorder, especially in children, it can
      present as a severe, life-threatening event. Paediatricians need to be aware of
      this important, probably underdiagnosed disorder in order to implement
      appropriate early treatment. In this report, seven children with rhabdomyolysis
      of both forms, endogenous and exogenous, are presented. Despite comprehensive 'up
      to-date' investigations being performed on paediatric patients with endogenous
      (often recurrent) rhabdomyolysis, the majority of these patients' underlying
      disorders will remain undiagnosed. Overall, these patients usually have a very
      good prognosis even if repeated, severe life-threatening episodes occur. It is
      recommended that a regimen of early therapy with fluids and sodium bicarbonate be
      instituted in all patients with rhabdomyolysis.

PMID- 10940182
TI  - Acute thrombocytopenia associated with post-streptococcal acute
      glomerulonephritis.
AB  - A case of acute thrombocytopenia associated with post-streptococcal acute
      glomerulonephritis is described. The patient showed a mild glomerulonephritis and
      a remarkable increase of platelet-associated immunoglobulin G (PAIgG). The
      relation between the mild degree of glomerulonephritis and the high PAIgG value
      is discussed.

PMID- 10940183
TI  - Gastric aspiration and sleeping position in infancy and early childhood.
AB  - Concern has been expressed that the recommendation of supine sleeping position
      for infants would result in an increase in deaths due to gastric aspiration. A
      review of 196 cases of infant and early childhood death in children under 3 years
      of age, occurring over a 9-year period (September 1989 to August 1998) was
      undertaken to ascertain how many cases of significant gastric aspiration had
      occurred. Extensive and widespread filling of the airways/alveoli with gastric
      contents was found in three infants/young children aged 5, 6 and 30 months,
      respectively. In each instance the body had been found lying face down (prone),
      with the face in a pool of vomitus in at least one case. No cases of significant
      gastric aspiration were found in infants who had been found lying on their sides
      or backs (supine). In addition, no significant increase in numbers of infant and
      early childhood deaths in South Australia due to gastric aspiration over this
      time could be demonstrated. Concerns that the supine rather than the prone
      position is more likely to result in significant gastric aspiration are not
      supported by this study.

PMID- 10940184
TI  - Methaemoglobinaemia secondary to topical lignocaine/ prilocaine in a circumcised
      neonate.
AB  - The use of topical lignocaine/prilocaine (EMLA, Astra Pharmaceuticals, North
      Ryde, NSW, Australia) for pain relief for neonatal circumcision is becoming more
      prevalent. Because of immaturity of the methaemoglobin reductase pathway, the
      neonate is vulnerable to methaemoglobinaemia which is a recognized complication
      of prilocaine therapy. This is the second report of methaemoglobinaemia due to
      the use of EMLA in association with circumcision during the newborn period.

PMID- 10940185
TI  - A case of vaccine-associated paralytic poliomyelitis.
AB  - Vaccine-associated paralytic poliomyelitis (VAPP) is a very rare complication of
      oral polio vaccine (OPV), seen predominantly with first exposure to OPV.
      Reversion of vaccine strain poliovirus to a more neurovirulent strain of the
      virus is thought to be necessary for paralytic disease to occur. Vaccine
      associated poliomyelitis can occur in either recipients of the vaccine or in
      susceptible contacts. We describe an episode of VAPP in an infant in whom
      paralysis became evident at age 124 days, 14 days after administration of the
      second dose of OPV vaccine. The second dose of diphtheria-tetanus-pertussis-
      Haemophilus (DTPH) type-b vaccine had been given at the time of OPV
      administration, and the hepatitis B vaccine had been administered in the opposite
      leg. Paralysis was localized to the limb in which the DTPH had been injected.

PMID- 10940186
TI  - Severe hypothermia in a neonate following antenatal exposure to haloperidol.

PMID- 10940189
TI  - Preface.

PMID- 10940187
TI  - Acute generalized exanthematic pustulosis following administration of
      ceftriaxone.

PMID- 10940192
TI  - Preface.

PMID- 10940190
TI  - Editorial.

PMID- 10940193
TI  - Editorial.

PMID- 10940194
TI  - Adriana and Luisa Castellucci award lecture 1999: role of oxygen in the
      regulation of trophoblast gene expression and invasion.
AB  - Changes in oxygen levels characterize normal and pathological human placentation.
      For example, relatively low Po(2)values are present around the blastocyst during
      implantation and in the placenta of the first trimester of pregnancy, a time of
      maximal trophoblast invasion. Our studies have revealed that low oxygen levels
      stimulate the in vitro invasiveness of cultured first trimester trophoblasts.
      This increased invasive ability is linked to elevated expression of some
      components of the plasminogen activator system and requires the participation of
      a putative haem protein. As gestation proceeds beyond the first trimester, and
      the extent of trophoblast invasion decreases, placental oxygen levels rise with a
      corresponding increase in blood flow. However, during certain pathological
      conditions, such as pre-eclampsia/intrauterine growth restriction, impaired
      remodelling of the uterine spiral arterioles leads to vessels with reduced
      diameters and localized regions of placental ischaemia/hypoxia. Placental hypoxia
      in the second half of gestation, as a consequence of reduced uteroplacental blood
      flow, may result in aberrant expression of genes that contribute to the
      pathophysiology of pre-eclampsia. Some of these genes encode certain cytokines
      and vasoactive molecules. We have also identified other genes whose expression is
      regulated by oxygen. Expression of one of them is induced in trophoblast and
      other cell types cultured under low oxygen levels and the product of the gene is
      a 43-kDa protein which we have termed PROXY-1. Compared to placental tissues and
      membranes isolated from uncomplicated pregnancies, PROXY-1 expression is elevated
      in tissues from pre-eclamptic pregnancies such as chorionic villi of peri-infarct
      regions, basal plate and membrane decidua, as well as chorion. Overall, these
      observations suggest that oxygen levels play an important role in placentation
      and in the pathophysiology of certain complications of pregnancy.

PMID- 10940195
TI  - Current topic: the role of growth hormone and insulin-like growth factors for
      placental growth and development.

PMID- 10940196
TI  - Current topic: the uteroplacental renin-angiotensin system.
AB  - The components of the renin-angiotensin system (RAS) are expressed in the
      uteroplacental unit. The expression varies between species, probably due to the
      marked species differences in placental architecture. The conditions for
      angiotensin (Ang) II formation exist and Ang II receptors are present throughout
      the human uteroplacental unit, indicating the presence of a functional local RAS.
      The uteroplacental RAS interacts with other regulatory systems and in this way
      modulates various aspects of tissue function. It is suggested that the
      uteroplacental RAS is important for the regeneration of the endometrium after
      shedding, and for decidualization, implantation and placentation. The RAS
      participates in the regulation of the uteroplacental blood flow, prostaglandin
      synthesis and oestradiol secretion. Disturbances of the uteroplacental RAS may
      lead to dysfunctional bleeding and to reduced uteroplacental blood flow in
      pregnancies complicated by pre-eclampsia and intrauterine growth retardation.

PMID- 10940197
TI  - Temporal expression of prostaglandin H synthase type 2 (PGHS-2) and P450(C17)in
      ovine placentomes with the natural onset of labour.
AB  - Labour in the sheep is preceded by increased tissue and plasma prostaglandin (PG)
      concentrations, and PGs could potentially contribute to the regulation of
      P450(C17)in placental tissue. Therefore, we determined the cellular localization
      and temporal pattern of expression of P450(C17)and prostaglandin H synthase type
      2 (PGHS-2), the primary PG synthetic enzyme, in intrauterine tissues from three
      groups of pregnant ewes at term; animals not in labour (NIL;n=5; 140-145 days of
      gestation), animals in early labour (EL;n=6; 143-149 days) and animals in active
      labour (L;n=6; 145-149 days). Allocation of animals into the three groups was
      based on continuous monitoring and assessment of myometrial contractile activity
      (EMG) and changes in the intrauterine pressure (IUP). Levels of mRNA encoding
      PGHS-2 and P450C17 were determined by in situ hybridization. Localization and
      levels of immunoreactive (ir-) P450(C17)and ir-PGHS-2 protein were determined by
      immunohistochemistry and Western blotting. PGHS-2 mRNA and ir-PGHS-2 were already
      elevated in placentomes of NIL animals and did not increase further with the
      progression of labour, whereas P450C17 mRNA increased progressively with labour,
      and ir-P450C17 rose significantly only in animals in active labour. The rise in
      P450C17 expression corresponded temporally to a progressive increase in maternal
      plasma concentration of oestradiol. We suggest that the temporal relationship and
      subsequent co-localization of PGHS-2 and P450(C17)proteins in the uninucleate
      trophoblast cells of the placentomes are consistent with the possibility that
      placental PGs could act to enhance placental output of oestrogen leading to
      labour and delivery.

PMID- 10940198
TI  - Correlation between second trimester maternal serum inhibin-A and human chorionic
      gonadotrophin for the prediction of pre-eclampsia.
AB  - We aimed to investigate the relationship between inhibin-A and human chorionic
      gonadotrophin (hCG) concentrations in the second trimester in the same cohort of
      women and compare their screening efficiency for the subsequent development of
      pre-eclampsia. The main outcome measures were pre-eclampsia and pre-eclampsia
      requiring delivery before 37 weeks.We carried out a retrospective examination of
      inhibin-A and free beta-hCG levels taken between 15 and 19 weeks of gestation,
      from 685 women. The values were corrected for weight and gestation and presented
      as multiples of the median (MoM). Receiver operator characteristic (ROC) curves
      for the prediction of pre-eclampsia and pre-eclampsia requiring delivery before
      37 weeks were created for both analytes alone and in combination. Based on this
      data the sensitivities for the prediction of pre-eclampsia using inhibin-A and
      hCG, alone and in combination were examined for a specificity of 90 per
      cent.Thirty-five (5.5 per cent) women developed pre-eclampsia, of whom 15 (2.7
      per cent) required delivery before term as a result of pre-eclampsia. There was
      no correlation between inhibin-A and hCG for the whole population (r=0.08) but
      there was a significant correlation for women who subsequently developed pre
      eclampsia (r=0.648) or preterm pre-eclampsia (r=0.84). For a specificity of 90
      per cent the sensitivity using inhibin-A was significantly better than for hCG
      (48.6 per cent versus 31.4 per cent, P< 0.05). The results were similar for
      preterm pre-eclampsia (P< 0.05). The addition of hCG data to inhibin-A data did
      not improve the sensitivity for pre-eclampsia compared to inhibin-A alone (42.9
      per cent versus 48.6 per cent, P< 0.20).Inhibin-A is a more sensitive marker for
      the subsequent development of pre-eclampsia than hCG. Addition of hCG data to
      inhibin-A did not improve the screening efficacy for pre-eclampsia suggesting
      that inhibin-A and hCG are markers of the same underlying pathological process.

PMID- 10940199
TI  - Telomerase activity and apoptosis as indicators of ageing in placenta with and
      without intrauterine growth retardation.
AB  - Telomerase activity (TA) and apoptosis were analysed in placenta with and without
      intrauterine growth retardation (IUGR). Thirty-one specimens were taken from
      chorionic villi in the first trimester (Group A), 32 placenta specimens were
      obtained from cases without IUGR in second and third trimester (Group B) and 12
      specimens of placenta tissue were obtained from cases of asymmetric IUGR between
      26 and 39 weeks of gestation (Group C). TA was analysed by the Telomeric Repeat
      Amplification Protocol (TRAP) and in situ TRAP assay. Apoptotic changes were
      assessed by immunohistochemical staining using Bcl-2 monoclonal antibody and by
      terminal transferase-mediated in situ end-labelling (TUNEL). TA was detected in
      29 of the 31 (93.5 per cent) chorionic villi (Group A) and in 20 of the 32 (62.5
      per cent) placenta without IUGR (Group B), whereas weak TA was observed in the
      placenta of all 12 asymmetric IUGR cases (Group C). Significantly higher Bcl-2
      immunoreactivity was observed in trophoblastic cells of Group A (85.9+/-4.2 per
      cent) and Group B (72.8+/-7.2 per cent) than Group C (54.84+/-4.83 per cent),
      while TUNEL positive cells were identified at a significantly higher frequency in
      the trophoblastic cells of Group C (9.7+/-7.4 per cent) than Group A (1.1+/-1.9
      per cent) or Group B (2.9+/-3.7 per cent).

PMID- 10940200
TI  - Purification and partial characterization of peroxidase from human term placenta
      of non-smokers: metabolism of benzo(a)pyrene-7, 8-dihydrodiol.
AB  - Peroxidase (Donor: H(2)O(2)oxidoreductase EC 1.11.1.7) from human term placentae
      of non-smokers was purified to homogeneity by a combination of NH(4)Cl
      extraction, affinity chromatography, (NH(4))(2)SO(4)precipitation, ion-exchange
      and gel filtration chromatography. The homogeneity of purified human placental
      peroxidase (HTPP) was confirmed by gel filtration, reverse phase high performance
      liquid chromatography (HPLC) and SDS-PAGE. Peroxidase was found to be a membrane
      bound enzyme. A high concentration of NH(4)Cl (1.2 m) was needed to extract and
      solublize the enzyme. Removal of the salt resulted in irreversible precipitation
      of the enzyme. The protein exhibited a molecular mass of 126 000 kDa according to
      gel filtration and approximately 60 000 kDa by SDS-PAGE, indicating that the
      peroxidase is a homodimer. The purified peroxidase showed an optimum pH range of
      7 to 8.5 and the K(m)for H(2)O(2)and guaiacol were found to be 0.08 m m and 10.0
      m m, respectively. The purified peroxidase oxidized several substrates, namely
      potassium iodide, tetramethyl benzidine, guaiacol, ortho dianisidne and tyrosine.
      The enzyme was resistant to thermal denaturation up to 70 degrees C and also to
      chaotropic agents, guanidinium chloride and urea. Spectral properties indicated
      the presence of Soret band at 433 which shifted to 451 nm on complexation with
      cyanide. The circular dichroism studies showed that HTPP has a predominantly
      helical secondary structure. The enzyme showed similarities to the
      myeloperoxidase with regard to spectral and catalytical properties but differed
      significantly in amino acid composition, the R(z)value and molecular mass.
      Purified HTPP differed from eosinophil peroxidase in all physico-chemical
      properties indicating that it is not of eosinophil origin, but may represent a
      distinct, constitutive peroxidase in human placenta. Further, purified peroxidase
      catalyzed oxidation of benzo(a)pyrene-7, 8-dihydrodiol in presence of tyrosine
      and hydrogen peroxide to BP-tetrols, the hydrolytic products of BP-diol-epoxides,
      demonstrating the ability of peroxidase in bioactivation of benzo(a)pyrene in
      human placenta.

PMID- 10940201
TI  - Heat produces uteroplacental circulatory disturbance in pregnant rats through
      action of corticotropin releasing hormone (CRH).
AB  - There is some evidence showing an existence of corticotropin releasing hormone
      (CRH) and opioid peptides, including beta-endorphin (betaEP), in human placenta,
      whereas physiological roles of the placental peptides in response to stress
      remain to be elucidated. To clarify the involvement of CRH and opioid system in
      the uteroplacental circulation in the pregnant rats exposed to heat, we examined
      the effects of heat and intravenous administration of CRH receptor antagonist
      alpha-helical CRH (9-41) on the uteroplacental blood flow, as well as blood CRH,
      and blood and placental betaEP in pregnant rats. Heat did not change uterine
      blood flow in virgin rats, but reduced uteroplacental blood flow in pregnant
      rats. The reduced uteroplacental blood flow induced by heat in pregnant rats was
      reversed by the administration of alpha-helical CRH. Independent of the status of
      pregnancy, heat increased blood CRH, which was not reversed by alpha-helical CRH.
      Although heat did not change placental betaEP, alpha-helical CRH reduced blood
      and placenta betaEP in pregnant rats. These results suggest that the
      uteroplacental circulatory disturbance caused by heat is mediated by CRH,
      possibly through the involvement of CRH receptor in rat placenta. The placental
      opioid system seems unlikely to be involved in the mediation of uteroplacental
      circulation.

PMID- 10940202
TI  - Expression of endothelial and inducible nitric oxide synthases and nitric oxide
      production in ovine placental and uterine tissues during late pregnancy.
AB  - We evaluated the expression of endothelial (eNOS) and inducible (iNOS) nitric
      oxide (NO) synthases, NO production, and the role of angiotensin II (ANG II) in
      regulating NO production during late ovine pregnancy (day 110-142). Samples of
      the following tissues were obtained: fetal [cotyledonary (COT)] and maternal
      [caruncular (CAR)] portions of the placentoma, intercotyledonary fetal
      chorioallantoic membrane (ICOT) and intercaruncular maternal endometrium (ICAR).
      Using immunohistochemistry, eNOS positive staining was detected in all four
      tissues, primarily in the endothelium, chorioallantoic membrane, and luminal and
      glandular epithelium. For iNOS, the positive staining was observed primarily in
      stromal cells in ICOT and ICAR. Expression of eNOS and iNOS proteins was
      confirmed in COT using Western immunoblot. eNOS protein levels increased (P<
      0.05) approximately 3.5-fold from day 110 to 130 and then declined at term,
      whereas no change in iNOS protein levels was observed throughout the days
      studied. The tissue explants of COT, CAR, ICOT and ICAR were cultured in media in
      the absence or presence of ANG II (10(-9)or 10(-7) m) for 24 h. Total NO (nitrate
      and nitrite) levels in the explant-conditioned media were determined by
      chemiluminesence. In fetal COT, total NO levels increased (P< 0.05) 3.5-fold from
      day 110 to 130 and then declined (P< 0.05) at term. In ICOT, total NO levels
      exhibited a gradually increasing trend (r(2)=0.96, P< 0.01) from day 110 to days
      130 and 142. In maternal CAR, total NO levels were higher (P< 0.05) on day 130
      than those on days 120 and 142, whereas no change in total NO levels was observed
      in ICAR. ANG II at 10(-7) m treatment decreased (P< 0.05) total NO levels in COT
      on day 130. Thus, during late ovine pregnancy: (1) eNOS is expressed in COT, CAR,
      ICOT and ICAR while iNOS is primarily seen in stromal cells of ICOT and ICAR; (2)
      NO production by COT exhibits a biphasic pattern and parallels the changes in
      eNOS, but not iNOS protein levels, suggesting that eNOS is a predominant NOS
      isoform for the NO production; and (3) ANG II may contribute partially to
      decreases in NO production by COT at term.

PMID- 10940203
TI  - TNF-alpha/TNFRI in primary and immortalized first trimester cytotrophoblasts.
AB  - During the first trimester of pregnancy endogenous expression of tumour necrosis
      factor (TNF)-alpha has been detected in villous, as well as in proliferating and
      invading extravillous, trophoblasts suggesting that the protein could be involved
      in trophoblast differentiation. To gain insights into the putative role of the
      TNF-alpha signalling pathway, we investigated expression of its receptors, TNFR I
      and II, in first trimester placentae and early trophoblasts, and studied the
      influence of the cytokine on cell proliferation and apoptosis. ELISA and RT-PCR
      revealed secretion/expression of TNFRI protein/mRNA in immortalized ED27 cells
      and purified first trimester cytotrophoblasts, while soluble TNFRII was
      undetectable in cell culture supernatants. In agreement, immunohistochemical
      analyses of first trimester placentae showed that TNFRI is localized to the
      villous cyto- and syncytiotrophoblast, to the proliferating cytotrophoblasts of
      the cell islands and cell columns, as well as to extravillous cells invading
      decidual tissue. TNFRII, however, was absent in early trophoblast populations.
      Interleukin (IL)-1 and phorbol 12-myristate 13-acetate (PMA) induced shedding of
      TNFRI from ED27 and primary cells suggesting that under inflammatory conditions
      the soluble receptor protein may protect from cytotoxic effects of TNF-alpha.
      Upon incubation with increasing amounts of TNF-alpha no significant changes in
      DNA-content or cell numbers were found, suggesting that the cytokine does not
      augment proliferation of primary cytotrophoblasts. High doses of TNF-alpha,
      however, provoked growth arrest in ED27 cells as evaluated by cell counting, but
      did not induce necrosis/apoptosis as was assessed by TUNEL assay. In first
      trimester cells addition of elevated amounts of TNF-alpha resulted in the
      appearance of TUNEL-positive cells and an increase in caspase-3 enzyme activity
      suggesting that the TNF-alpha-dependent apoptotic cascade is executed in a
      portion of the early cytotrophoblasts.

PMID- 10940204
TI  - Endothelin A and B receptors change their expression levels during development of
      human placental villi.
AB  - Endothelin receptors have recently been found in non-vascular tissues including
      the human placenta. The present study investigated developmental changes in
      location and expression levels of endothelin A and B receptors (ETA-R, ETB-R) in
      human placentae and isolated trophoblast by comparing first and third trimester
      tissues. In the first trimester all cells and tissues were immunolabelled for ETA
      R and ETB-R, whereas in third trimester placentae the syncytiotrophoblast (ETA-R,
      ETB-R) and macrophages (ETA-R) were unstained. Immunoblotting for both receptors
      revealed up to three bands at 33-35, 50 and 75 kDa, respectively, which were
      differentially present in the first and third trimester. Pre-adsorption of
      antibodies with oligopeptides used for antigen-generation weakened the
      immunoreactions. ETA-R protein levels decreased (P< 0.05) in total villous tissue
      and isolated trophoblast, whereas ETB-R was unchanged. ETB-R transcripts (RT-PCR)
      prevailed in both stages and tissues, but in contrast to the protein levels its
      preponderance decreased from first trimester to term in villous tissue (P< 0.01),
      because of a four to five-fold increase in ETA-R and only a two-fold (P< 0.05)
      increase in ETB-R mRNA levels (P< 0.01). We conclude that ET receptor location,
      intracellular processing and expression levels in human villous tissue change
      between the first and third trimester. This may reflect changing functions of ET
      1 during placental development.

PMID- 10940205
TI  - Molecular organization of tight and adherens junctions in the human placental
      vascular tree.
AB  - Tight and adherens junctions are major determinants of endothelial integrity.
      Molecules present therein have been implicated in vascular permeability,
      stability of junctions, angiogenesis and intracellular signalling. Using
      immunofluorescence and confocal scanning microscopy, the adherens junctions (AJs)
      in human placental vessels were found to contain the entire cadherin-catenin
      complex predicted from in vitro studies. Vascular endothelial cadherin (VE
      cadherin) clusters were co-localized with beta-catenin, an important signal
      transduction ligand, and with alpha-catenin, which is thought to link the complex
      to the peri-junctional actin. Antibodies to plakoglobin, a molecule shown to be a
      component of stable adherens junctions, revealed immunoreactivity in clefts of
      stromal villous vessels, but weak or negative immunoreactivity in intermediate
      and terminal villi. Tight junctional molecules demonstrated a differential
      surface expression. Within the same villous tree, arteries, veins and arterioles
      contained occludin but the exchange vessels in terminal villi were
      immunonegative. ZO-1, however, was present throughout. Ultrastructurally, there
      were no differences in frequency, position or dimension of tight junctions in
      these vessels. They showed a consistent 4 nm separation between outer membrane
      leaflets regardless of their location in the vascular tree. Occludin is not
      necessary for formation of tight junctions in the placenta; it may have an
      accessory role providing stability or added adhesiveness to tight junctions of
      large vessels. Its absence in terminal villous microvessels, along with the weak
      plakoglobin immunoreactivity in AJs, suggest that the junctions here are less
      stable. This may allow the increased plasticity necessary in terminal villi for
      continual growth, proliferation and solute exchange.

PMID- 10940207
TI  - Scanning electron microscopy of the microcotyledonary placenta of the horse
      (Equus caballus) in the latter half of gestation.
AB  - Scanning electron microscopy was used to examine the microstructure of the
      maternal and fetal placenta from 25 pregnant ponies (Equus caballus) throughout
      the second half of gestation. Samples of placenta, 2-6 cm(2)in area, were
      collected from the antimesometrial region of the pregnant horn at 105 days (n=1),
      165-219 days (n=5), 260 days (n=3), 270-277 days (n=3), 313-337 days (n=11) and
      immediately after spontaneous delivery at term (n=2). The maternal microcaruncle
      appears to be created from a clustering of about 16 uterine crypts encapsulated
      in a connective tissue sheath. There is a gestational increase in the depth of
      the microcaruncle during the second half of pregnancy. The fetal microcotyledon
      appears to be formed by a clustering of individual fetal villi. The length and
      branching of the villi increased considerably during the last 2-3 months of
      gestation. Tufts of from three to six branches were seen arising from close to
      the base of a villous stem. Branching of the villous stem occurred not only at
      the base but also along the secondary and tertiary branches. There was evidence
      of continued branching at the tips of the villi in the few days before birth.

PMID- 10940206
TI  - Transport of large neutral amino acids into BeWo cells.
AB  - BeWo choriocarcinoma cells were cultured onto solid microcarrier beads, packed
      into columns and superfused. Unidirectional influx of l -phenylalanine (l -phe)
      and l -leucine (l -leu) across the microvillous border of the cells was studied
      using a rapid paired-tracer dilution technique. Influx of l -phe and l -leu
      comprised both saturable and non-saturable components. K(m)values for l -phe and
      l -leu were 0.57+/-0.01 m m and 0.05+/-0.01 m m, respectively, with V(max)values
      of 120.4+/-0.5 nmol/mg/min and 41. 7+/-0.2 nmol/mg/min. Non-saturable uptake
      components were 29.0+/-0.1 nmol/mg/m m and 37.9+/-0.1 nmol/mg/min/m m
      respectively. l -leu uptake was found to be sodium-independent. The uptake of l 
      [(3)H]phe was strongly inhibited (90-100 per cent) by unlabelled l -phe, d -phe,
      l -leu or 2-aminoendobicyclo-[2,2, 1]-heptane-2-carboxylic acid (BCH) but not by
      l -arginine (l -arg) or methyl alpha-aminoisobutric acid (Me-AIB). Pre-incubation
      of Bewo cultures for 24 h in the presence of an additional 1.2 m ml -phe
      (simulating maternal phenylketonuria) significantly reduced both the K(m)and
      V(max)components of l -phe influx. l -arg (2 m m) had no effect on l -leu influx
      whereas 2 m ml -phe completely inhibited saturable l -leu influx. These data
      suggest that the microvillous border of differentiated BeWo cells transport large
      neutral amino acids predominantly via system L rather than by B(0) or y(+)L
      transporters.

PMID- 10940208
TI  - A unique exocelom-like space during early pregnancy in the horse.
AB  - The free allantois and allantochorion of conceptuses from 17 mares between 20 and
      90 days of gestation were examined to determine the manner in which the
      associated mesodermal derivatives differentiated. It was found that a robust
      basement membrane developed under the allantoic endoderm, and that this basement
      membrane was partially isolated from the vascular layer of the allantois by a
      mesothelial layer and an exocelom-like space. The exocelom-like space persisted
      until approximately the stage of villous formation, and remnants of the space
      persisted over larger allantoic vessels even later. It is suggested that
      originally the presence of the mesothelial layer facilitates type I collagen
      formation in the thick basement membrane under the basal lamina of the allantoic
      endoderm. The basement membrane maintains the integrity of the allantois while
      the underlying space allows some slippage between the allantois and its vascular
      layer which is more closely associated with the endometrial and exocelomic
      surfaces, respectively.

PMID- 10940210
TI  - Placentae with haemophagous zones and water channel proteins; a cautionary tale.

PMID- 10940211
TI  - Parental PGM(1)and gestational length of live-born infants from couples with
      primary repeated spontaneous abortions.

PMID- 10940209
TI  - Short communication: trophoblast proliferation is increased in chorionic villi
      from pregnancies with fetal trisomy 18.
AB  - Pregnancies with fetal trisomy 18 suffer from severe intrauterine growth
      restriction from the first trimester. This cross-sectional study of chorionic
      villi obtained from ongoing singleton pregnancies at 10-14 weeks of gestation,
      semiquantitatively examines chorionic villus stromal and trophoblastic cell
      proliferation rates in ongoing chromosomally normal and trisomy 18 pregnancies.
      Chorionic villi were stained using a standard immunohistochemistry protocol with
      a monoclonal antibody to the Ki-67 antigen and the number of Ki-67 positive
      trophoblastic and stromal cells per villous cross-section was compared between
      groups. The number of Ki-67 positive trophoblastic and stromal cells was
      significantly higher in the group (n=10) with trisomy 18 compared to the
      chromosomally normal group (n=25;t=2.1, P=0.03 and t=5.3, P<0.001 respectively).
      Abnormalities in control of cell turnover during development may be important in
      the pathogenesis of the clinical features of trisomic pregnancies.

PMID- 10940212
TI  - Glucose production and glucose-6-phosphatase in the human placenta.

PMID- 10940215
TI  - Preface.

PMID- 10940214
TI  - Letter to the editor: response to Dr Lala's letter-The effects of angiogenic
      growth factors on extravillous trophoblast invasion and motility

PMID- 10940213
TI  - The effects of angiogenic growth factors on extravillous trophoblast invasion and
      motility.

PMID- 10940216
TI  - Twist and sheet: variations on the theme of amyloid

PMID- 10940217
TI  - Review: history of the amyloid fibril.
AB  - Rudolph Virchow, in 1854, introduced and popularized the term amyloid to denote a
      macroscopic tissue abnormality that exhibited a positive iodine staining
      reaction. Subsequent light microscopic studies with polarizing optics
      demonstrated the inherent birefringence of amyloid deposits, a property that
      increased intensely after staining with Congo red dye. In 1959, electron
      microscopic examination of ultrathin sections of amyloidotic tissues revealed the
      presence of fibrils, indeterminate in length and, invariably, 80 to 100 A in
      width. Using the criteria of Congophilia and fibrillar morphology, 20 or more
      biochemically distinct forms of amyloid have been identified throughout the
      animal kingdom; each is specifically associated with a unique clinical syndrome.
      Fibrils, also 80 to 100 A in width, have been isolated from tissue homogenates
      using differential sedimentation or solubility. X-ray diffraction analysis
      revealed the fibrils to be ordered in the beta pleated sheet conformation, with
      the direction of the polypeptide backbone perpendicular to the fibril axis (cross
      beta structure). Because of the similar dimensions and tinctorial properties of
      the fibrils extracted from amyloid-laden tissues and amyloid fibrils in tissue
      sections, they have been assumed to be identical. However, the spatial
      relationship of proteoglycans and amyloid P component (AP), common to all forms
      of amyloid, to the putative protein only fibrils in tissues, has been unclear.
      Recently, it has been suggested that, in situ, amyloid fibrils are composed of
      proteoglycans and AP as well as amyloid proteins and thus resemble connective
      tissue microfibrils. Chemical and physical definition of the fibrils in tissues
      will be needed to relate the in vitro properties of amyloid protein fibrils to
      the pathogenesis of amyloid fibril formation in vivo.

PMID- 10940218
TI  - Review: amyloidogenesis-unquestioned answers and unanswered questions.
AB  - Current assumptions and conclusions in several active areas of amyloid research
      are examined to see how consistent the data from chosen in vitro and in vivo
      model systems are with clinical and anatomic observations. These areas include
      the assembly of amyloid-like fibrils in vitro, the nucleation phenomenon, amyloid
      fibril structure in vivo and in vitro, common structural components of the
      amyloids, and the regression of tissue amyloid and proteolysis of amyloid
      proteins. Divergences and congruencies are highlighted, which in turn suggests
      caution in the interpretation of present data, greater collaboration and
      communication among investigators, and, additional areas and techniques for
      investigation.

PMID- 10940219
TI  - Probing the kinetics of beta-amyloid self-association.
AB  - Spontaneous conversion of beta-amyloid peptide (Abeta) from soluble monomer to
      insoluble fibrillar precipitate may underlie the neurodegeneration associated
      with Alzheimer's disease. A complete description of Abeta self-association
      kinetics requires identification of the oligomeric species present and the
      pathway of association, as well as quantitation of rate constants and reaction
      order. Previously published work delineating progress in developing quantitative
      kinetic models is reviewed briefly. The use of light scattering to probe Abeta
      fibril size and shape as a function of time and concentration is described. Data
      describing Abeta self-association at physiological pH starting from the urea
      denatured state are presented. High-molecular-weight species formed rapidly,
      within minutes of dilution. At 70 microM, the size of the major fibrillar species
      was virtually constant with time, whereas at 280 microM two populations were
      detected, each of which increased in size with time. Incipient precipitation,
      prior to the appearance of a visible solid phase, was detected reliably by
      dynamic light scattering. Surprisingly, precipitates appeared earliest at the
      lowest concentration, and the physical state of the precipitate changed markedly
      with concentration. A gel diffusion assay showed that monomer Abeta dissociates
      from preformed fibrils, indicating that reversible heterogeneous association must
      be incorporated into any realistic model of Abeta association.

PMID- 10940220
TI  - A beta fibrillogenesis: kinetic parameters for fibril formation from congo red
      binding.
AB  - Using Scatchard analysis, we have formulated as a function of time and pH the
      relationship between the binding of Congo red to Alzheimer's beta-amyloid and the
      aggregation number (i.e., monomer concentration within fibrils) as defined by
      nucleation-dependent self-assembly. This provides a basis on which to determine
      the kinetic parameters for fibril formation from the observed concentration of
      bound Congo red.

PMID- 10940221
TI  - The Alzheimer's peptide a beta adopts a collapsed coil structure in water.
AB  - The self-assembly of the soluble peptide Abeta into Alzheimer's disease amyloid
      is believed to involve a conformational change. Hence the solution conformation
      of Abeta is of significant interest. In contrast to studies in other solvents, in
      water Abeta is collapsed into a compact series of loops, strands, and turns and
      has no alpha-helical or beta-sheet structure. Conformational stabilization is
      primarily attributed to van der Waals and electrostatic forces. A large
      conspicuous uninterrupted hydrophobic patch covers approximately 25% of the
      surface. The compact coil structure appears meta-stable, and because
      fibrillization leads to formation of intermolecular beta-sheet secondary
      structure, a global conformational rearrangement is highly likely. A molecular
      hypothesis for amyloidosis includes at least two primary driving forces, changes
      in solvation thermodynamics during formation of amyloid deposits and relief of
      internal conformational stress within the soluble precursor during formation of
      lower-energy amyloid fibrils.

PMID- 10940222
TI  - Solution structures in aqueous SDS micelles of two amyloid beta peptides of A
      beta(1-28) mutated at the alpha-secretase cleavage site (K16E, K16F).
AB  - NMRsolution structures are reported for two mutants (K16E, K16F) of the soluble
      amyloid beta peptide Abeta(1-28). The structural effects of these mutations of a
      positively charged residue to anionic and hydrophobic residues at the alpha
      secretase cleavage site (Lys16-Leu17) were examined in the membrane-simulating
      solvent aqueous SDS micelles. Overall the three-dimensional structures were
      similar to that for the native Abeta(1-28) sequence in that they contained an
      unstructured N-terminus and a helical C-terminus. These structural elements are
      similar to those seen in the corresponding regions of full-length Abeta peptides
      Abeta(1-40) and Abeta(1-42), showing that the shorter peptides are valid model
      systems. The K16E mutation, which might be expected to stabilize the macrodipole
      of the helix, slightly increased the helix length (residues 13-24) relative to
      the K16F mutation, which shortened the helix to between residues 16 and 24. The
      observed sequence-dependent control over conformation in this region provides an
      insight into possible conformational switching roles of mutations in the amyloid
      precursor protein from which Abeta peptides are derived. In addition, if
      conformational transitions from helix to random coil to sheet precede aggregation
      of Abeta peptides in vivo, as they do in vitro, the conformation-inducing effects
      of mutations at Lys16 may also influence aggregation and fibril formation.

PMID- 10940223
TI  - Review: model peptides and the physicochemical approach to beta-amyloids.
AB  - beta-Amyloid peptides are the main protein components of neuritic plaques and may
      be important in the pathogenesis of Alzheimer's Disease. The determination of the
      structure of beta-amyloid fibrils poses a challenge because of the limited
      solubility of beta-amyloid peptides and the noncrystalline nature of fibrils
      formed from these peptides. In this paper, we describe several physicochemical
      approaches which have been used to examine fibrils and the fibrillogenesis of
      peptide models of beta-amyloid. Recent advances in solid state NMR, such as the
      DRAWS pulse sequence, have made this approach a particularly attractive one for
      peptides such as beta-amyloid, which are not yet amenable to high-resolution
      solution phase NMR and crystallography. The application of solid state NMR
      techniques has yielded information on a model peptide comprising residues 10-35
      of human beta-amyloid and indicates that in fibrils, this peptide assumes a
      parallel beta-strand conformation, with all residues in exact register. In
      addition, we discuss the use of block copolymers of Abeta peptides and
      polyethylene glycol as probes for the pathways of fibrillogenesis. These methods
      can be combined with other new methods, such as high-resolution synchrotron X-ray
      diffraction and small angle neutron and X-ray scattering, to yield structural
      data of relevance not only to disease, but to the broader question of protein
      folding and self-assembly.

PMID- 10940224
TI  - Activation barriers to structural transition determine deposition rates of
      Alzheimer's disease a beta amyloid.
AB  - Brain amyloid composed of the approximately 40-amino-acid human beta-amyloid
      peptide A beta is integral to Alzheimer's disease pathology. To probe the
      importance of a conformational transition in Abeta during amyloid growth, we
      synthesized and examined the solution conformation and amyloid deposition
      activity of A beta congeners designed to have similar solution structures but to
      vary substantially in their barriers to conformational transition. Although all
      these peptides adopt similar solution conformations, a covalently restricted
      Abeta congener designed to have a very high barrier to conformational
      rearrangement was inactive, while a peptide designed to have a reduced barrier to
      conformational transition displayed an enhanced deposition rate relative to wild
      type A beta. The hyperactive peptide, which is linked to a heritable A beta
      amyloidosis characterized by massive amyloid deposition at an early age,
      displayed a reduced activation barrier to deposition consistent with a larger
      difference in activation entropy than in activation enthalpy relative to wild
      type A beta. These results suggest that in Alzheimer's disease, as in the prion
      diseases, a conformational transition in the depositing peptide is essential for
      the conversion of soluble monomer to insoluble amyloid, and alterations in the
      activation barrier to this transition affect amyloidogenicity and directly
      contribute to human disease.

PMID- 10940225
TI  - Review: Alzheimer's amyloid beta-peptide-associated free radical oxidative stress
      and neurotoxicity.
AB  - Alzheimer's disease, the major dementing disorder of the elderly that affects
      over 4 million Americans, is related to amyloid beta-peptide, the principal
      component of senile plaques in Alzheimer's disease brain. Oxidative stress,
      manifested by protein oxidation and lipid peroxidation, among other alterations,
      is a characteristic of Alzheimer's disease brain. Our laboratory united these two
      observations in a model to account for neurodegeneration in Alzheimer's disease
      brain, the amyloid beta-peptide-associated oxidative stress model for
      neurotoxicity in Alzheimer's disease. Under this model, the aggregated peptide,
      perhaps in concert with bound redox metal ions, initiates free radical processes
      resulting in protein oxidation, lipid peroxidation, reactive oxygen species
      formation, cellular dysfunction leading to calcium ion accumulation, and
      subsequent neuronal death. Free radical antioxidants abrogate these findings.
      This review outlines the substantial evidence from multiidisciplinary approaches
      for amyloid beta-peptide-associated free radical oxidative stress and
      neurotoxicity and protection against these oxidative processes and cell death by
      free radical scavengers. In addition, we review the strong evidence supporting
      the notion that the single methionine residue of amyloid beta-peptide is vital to
      the oxidative stress and neurotoxicological properties of this peptide. Further,
      we discuss studies that support the hypothesis that aggregated soluble amyloid
      beta-peptide and not fibrils per se are necessary for oxidative stress and
      neurotoxicity associated with amyloid beta-peptide.

PMID- 10940226
TI  - Chelation and intercalation: complementary properties in a compound for the
      treatment of Alzheimer's disease.
AB  - Selective application of metal chelators to homogenates of human Alzheimer's
      disease (AD) brain has led us to propose that the architecture of aggregated beta
      amyloid peptide, whether in the form of plaques or soluble oligomers, is
      determined at least in part by high-affinity binding of transition metals,
      especially copper and zinc. Of the two metals, copper is implicated in reactive
      oxygen species generating reactions, while zinc appears to be associated with
      conformational and antioxidant activity. We tested the copper chelators
      trientine, penicillamine, and bathophenanthroline for their ability to mobilize
      brain Abeta as measured against our benchmark compound bathocuproine (BC). All of
      these agents were effective in solubilizing brain Abeta, although BC was the most
      consistent across the range of AD brain tissue samples tested. Similarly, all of
      the copper chelators depleted copper in the high-speed supernatants. BC alone had
      no significant effect upon zinc levels in the soluble fraction. BC extraction of
      brain tissue from C100 transgenic mice (which express human Abeta but do not
      develop amyloid) revealed SDS-resistant dimers as Abeta was mobilized from the
      sedimentable to the soluble fraction. NMR analysis showed that, in addition to
      its copper chelating properties, BC interacts with Abeta to form a complex
      independent of the presence of copper. Such hybrid copper chelating and "chain
      breaking" properties may form the basis of a rational design for a therapy for
      Alzheimer's disease.

PMID- 10940228
TI  - Self-assembly of beta-amyloid 42 is retarded by small molecular ligands at the
      stage of structural intermediates.
AB  - Assemblyof the amyloid-beta peptide (Abeta) into fibrils and its deposition in
      distinct brain areas is considered responsible for the pathogenesis of
      Alzheimer's disease (AD). Thus, inhibition of fibril assembly is a potential
      strategy for therapeutic intervention. Electron cryomicroscopy was used to
      monitor the initial, native assembly structure of Abeta42. In addition to the
      known fibrillar intermediates, a nonfibrillar, polymeric sheet-like structure was
      identified. A temporary sequence of supramolecular structures was revealed with
      (i) polymeric Abeta42 sheets during the onset of assembly, inversely related to
      the appearance of (ii) fibril intermediates, which again are time-dependently
      replaced by (iii) mature fibrils. A cell-based primary screening assay was used
      to identify compounds that decrease Abeta42-induced toxicity. Hit compounds were
      further assayed for binding to Abeta42, radical scavenger activity, and their
      influence on the assembly structure of Abeta42. One compound, Ro 90-7501, was
      found to efficiently retard mature fibril formation, while extended polymeric
      Abeta42 sheets and fibrillar intermediates are accumulated. Ro 90-7501 may serve
      as a prototypic inhibitor for Abeta42 fibril formation and as a tool for studying
      the molecular mechanism of fibril assembly.

PMID- 10940227
TI  - Studies on the in vitro assembly of a beta 1-40: implications for the search for
      a beta fibril formation inhibitors.
AB  - The progressive deposition of the amyloid beta peptide (Abeta) in fibrillar form
      is a key feature in the development of the pathology in Alzheimer's disease (AD).
      We have characterized the time course of Abeta fibril formation using a variety
      of assays and under different experimental conditions. We describe in detail the
      morphological development of the Abeta polymerization process from pseudo
      spherical structures and protofibrils to mature thioflavin-T-positive/Congo red
      positive amyloid fibrils. Moreover, we structurally characterize the various
      polymorphic fibrillar assemblies using transmission electron microscopy and
      determine their mass using scanning transmission electron microscopy. These
      results provide the framework for future investigations into how target compounds
      may interfere with the polymerization process. Such substances might have a
      therapeutic potential in AD.

PMID- 10940230
TI  - Review: modulating factors in amyloid-beta fibril formation.
AB  - Amyloid formation is a key pathological feature of Alzheimer's disease and is
      considered to be a major contributing factor to neurodegeneration and clinical
      dementia. Amyloid is found as both diffuse and senile plaques in the parenchyma
      of the brain and is composed primarily of the 40- to 42-residue amyloid-beta
      (Abeta) peptides. The characteristic amyloid fiber exhibits a high beta-sheet
      content and may be generated in vitro by the nucleation-dependent self
      association of the Abeta peptide and an associated conformational transition from
      random to beta-conformation. Growth of the fibrils occurs by assembly of the
      Abeta seeds into intermediate protofibrils, which in turn self-associate to form
      mature fibers. This multistep process may be influenced at various stages by
      factors that either promote or inhibit Abeta fiber formation and aggregation.
      Identification of these factors and understanding the driving forces behind these
      interactions as well as the structural motifs necessary for these interactions
      will help to elucidate potential sites that may be targeted to prevent amyloid
      formation and its associated toxicity. This review will discuss some of the
      modulating factors that have been identified to date and their role in
      fibrillogenesis.

PMID- 10940229
TI  - Inhibition of beta-amyloid-induced neurotoxicity by imidazopyridoindoles derived
      from a synthetic combinatorial library.
AB  - Alzheimer's disease is a progressive neurodegenerative disorder characterized by
      the deposit of amyloid fibrils in the brain that result from the self-aggregative
      polymerization of the beta-amyloid peptide (Abeta). Evidence of a direct
      correlation between the ability of Abeta to form stable aggregates in aqueous
      solution and its neurotoxicity has been reported. The cytotoxic effects of Abeta
      have been attributed to the aggregation properties of a domain corresponding to
      the peptide fragment Abeta25-35. In an effort to generate novel inhibitors of
      Abeta neurotoxicity and/or aggregation, a mixture-based synthetic combinatorial
      library composed of 23 375 imidazopyridoindoles was generated and screened for
      inhibition of Abeta25-35 neurotoxicity toward the rat pheochromocytoma PC-12 cell
      line. The effect of the identified lead compounds on Abeta25-35 aggregation was
      then evaluated by means of circular dichroism (CD) and thioflavin-T fluorescence
      spectroscopy. Their activity against Abeta1-42 neurotoxicity toward the PC-12
      cell line was also determined. The most active imidazopyridoindoles inhibited
      both Abeta25-35 and Abeta1-42 neurotoxicity in the low- to mid-micromolar range.
      Furthermore, inhibition of the random coil to beta-sheet transition and self
      aggregation of Abeta25-35 was observed by CD and fluorescence spectroscopy,
      supporting the relationship between inhibition of the Abeta aggregation process
      and neurotoxicity.

PMID- 10940231
TI  - Abnormal tau-containing filaments in neurodegenerative diseases.
AB  - It has been known for some time that the neurofibrillary pathology in Alzheimer's
      disease consists of so-called paired helical and straight filaments made up of
      the microtubule-associated protein tau. The degree of dementia observed in the
      disease correlates better with the extent of neurofibrillary pathology than with
      the Abeta amyloid deposits, the other characteristic defining pathological
      fibrous deposit in Alzheimer's disease. However, no familial cases of Alzheimer's
      disease have been genetically linked to the tau protein locus. Recently a group
      of frontotemporal dementias with parkinsonism linked to chromosome 17 has been
      shown to be caused by mutations in the tau gene. Some are missense mutations
      giving altered tau proteins, whereas others affect the splicing of the pre-mRNA
      and change the balance between different tau isoforms. Histologically these
      diseases are all characterised by various kinds of filamentous tau protein
      deposits, mostly in the complete absence of Abeta deposits. The abnormal tau
      filaments show different morphologies, depending on the nature of the tau
      mutation. These diseases show that tau mutations can be a prime cause of
      inherited dementing illness and may throw some light on the pathological process
      in the much larger number of sporadic cases of Alzheimer's disease.

PMID- 10940232
TI  - Review: immunoglobulin light chain amyloidosis--the archetype of structural and
      pathogenic variability.
AB  - AL amyloidosis is caused by deposition in target tissue of amyloid fibrils
      constituted by monoclonal immunoglobulin light chains. The amyloidogenic plasma
      cells derive from a transformed memory B cell that can be identified by anti
      idiotype monoclonal antibodies. Comparison of the primary structures of
      amyloidogenic and nonamyloidogenic light chains does not show any common
      structural motif in the amyloidogenic variants but reveals peculiar replacements
      which can destabilize the folding state. Reduced folding stability now appears to
      be a unifying property of amyloidogenic light chains. The tendency of these
      proteins to populate a partially unfolded intermediate state is a key event in
      the self-association that progresses to the formation of oligomers and fibrils.
      The mechanism of organ damage caused by AL amyloid deposition is not known, but
      clinical findings suggest that the process of amyloid fibril formation itself
      exerts tissue toxic effects independently of the amount of amyloid deposited.
      Since the disease is caused by the neoplastic expansion of the plasma cell
      population synthesizing the amyloidogenic light chains, the clone represents the
      prime therapeutic target of conventional chemotherapy and experimental
      immunotherapy. In common with other types of amyloidosis the therapeutic strategy
      can take advantage of drugs able to improve the reabsorption of the amyloid
      deposits or able to bind and stabilize the light chain in the native-like folded
      state.

PMID- 10940233
TI  - Review: TTR amyloidosis-structural features leading to protein aggregation and
      their implications on therapeutic strategies.
AB  - Transthyretin amyloidosis represents a spectrum of clinical syndromes that, in
      all cases except senile systemic amyloidosis, are dependent on the mutation
      present in the transthyretin (TTR) protein. Although the role of amyloid deposits
      in the pathogenesis of the disease is not clear, preventing their formation or
      promoting their disaggregation is necessary to control the development of
      clinical symptoms. The design of therapies aiming at preventing amyloid formation
      or promoting its dissociation requires detailed knowledge of the fibrils'
      molecular structure and a complete view about the factors responsible for protein
      aggregation. This review is focused on the structural studies, performed on
      amyloid fibrils and amyloidogenic TTR variants, aiming at understanding the
      aggregation mechanism as well as the atomic structure of the fibril assembly.
      Based on the available information possible therapies are also surveyed.

PMID- 10940234
TI  - Review: formation and properties of amyloid-like fibrils derived from alpha
      synuclein and related proteins.
AB  - Synucleinsare small proteins that are highly expressed in brain tissue and are
      localised at presynaptic terminals in neurons. alpha-Synuclein has been
      identified as a component of intracellular fibrillar protein deposits in several
      neurodegenerative diseases, and two mutant forms of alpha-synuclein have been
      associated with autosomal-dominant Parkinson's Disease. A fragment of alpha
      synuclein has also been identified as the non-Abeta component of Alzheimer's
      Disease amyloid. In this review we describe some structural properties of alpha
      synuclein and the two mutant forms, as well as alpha-synuclein fragments, with
      particular emphasis on their ability to form beta-sheet on ageing and aggregate
      to form amyloid-like fibrils. Differences in the rates of aggregation and
      morphologies of the fibrils formed by alpha-synuclein and the two mutant proteins
      are highlighted. Interactions between alpha-synuclein and other proteins,
      especially those that are components of amyloid or Lewy bodies, are considered.
      The toxicity of alpha-synuclein and related peptides towards neurons is also
      discussing in relation to the aetiology of neurodegenerative diseases.

PMID- 10940235
TI  - Prions of yeast as heritable amyloidoses.
AB  - Two infectious proteins (prions) of Saccharomyces cerevisiae have been identified
      by their unusual genetic properties: (1) reversible curability, (2) de novo
      induction of the infectious prion form by overproduction of the protein, and (3)
      similar phenotype of the prion and mutation in the chromosomal gene encoding the
      protein. [URE3] is an altered infectious form of the Ure2 protein, a regulator of
      nitrogen catabolism, while [PSI] is a prion of the Sup35 protein, a subunit of
      the translation termination factor. The altered form of each is inactive in its
      normal function, but is able to convert the corresponding normal protein into the
      same altered inactive state. The N-terminal parts of Ure2p and Sup35p (the "prion
      domains") are responsible for prion formation and propagation and are rich in
      asparagine and glutamine residues. Ure2p and Sup35p are aggregated in vivo in
      [URE3]- and [PSI]-containing cells, respectively. The prion domains can form
      amyloid in vitro, suggesting that amyloid formation is the basis of these two
      prion diseases. Yeast prions can be cured by growth on millimolar concentrations
      of guanidine. An excess or deficiency of the chaperone Hsp104 cures the [PSI]
      prion. Overexpression of fragments of Ure2p or certain fusion proteins leads to
      curing of [URE3].

PMID- 10940236
TI  - Scrapie infectivity is independent of amyloid staining properties of the N
      terminally truncated prion protein.
AB  - The prion protein undergoes a profound conformational change when the cellular
      isoform (PrP(C)) is converted into the disease-causing form (PrP(Sc)). Limited
      proteolysis of PrP(Sc) produces PrP 27-30, which readily polymerizes into
      amyloid. To study the relationship between PrP amyloid and infectivity, we
      employed organic solvents that perturb protein conformation. Hexafluoro-2
      propanol (HFIP), which promotes alpha-helix formation, modified the
      ultrastructure of PrP amyloid and decreased the beta-sheet content as well as
      prion infectivity. HFIP reversibly decreased the binding of Congo red dye to the
      PrP amyloid rods while inactivation of prion infectivity was irreversible. In
      contrast, 1,1,1-trifluoro-2-propanol (TFIP) did not inactivate prion infectivity
      but like HFIP, TFIP did alter the morphology of the rods and abolished Congo red
      binding. Solubilization using various solvents and detergents produced monomeric
      and dimeric PrP that lacked infectivity. Proteinase K resistance of detergent
      treated PrP 27-30 showed no correlation with scrapie infectivity. Our results
      separate prion infectivity from the amyloid properties of PrP 27-30 and
      underscore the dependence of prion infectivity on PrP(Sc) conformation. These
      findings also demonstrate that the specific beta-sheet-rich structures required
      for prion infectivity can be differentiated from those required for amyloid
      formation.

PMID- 10940237
TI  - Amyloid fibril formation and seeding by wild-type human lysozyme and its disease
      related mutational variants.
AB  - Wild-type human lysozyme and its two stable amyloidogenic variants have been
      found to form partially folded states at low pH. These states are characterized
      by extensive disruption of tertiary interactions and partial loss of secondary
      structure. Incubation of the proteins at pH 2.0 and 37 degrees C (Ile56Thr and
      Asp67His variants) or 57 degrees C (wild-type) results in the formation of large
      numbers of fibrils over several days of incubation. Smaller numbers of fibrils
      could be observed under other conditions, including neutral pH. These fibrils
      were analyzed by electron microscopy, Congo red birefringence, thioflavine-T
      binding, and X-ray fiber diffraction, which unequivocally show their amyloid
      character. These data demonstrate that amyloidogenicity is an intrinsic property
      of human lysozyme and does not require the presence of specific mutations in its
      primary structure. The amyloid fibril formation is greatly facilitated, however,
      by the introduction of "seeds" of preformed fibrils to the solutions of the
      variant proteins, suggesting that seeding effects could be important in the
      development of systemic amyloidosis. Fibril formation by wild-type human lysozyme
      is greatly accelerated by fibrils of the variant proteins and vice versa, showing
      that seeding is not specific to a given protein. The fact that wild-type lysozyme
      has not been found in ex vivo deposits from patients suffering from this disease
      is likely to be related to the much lower population of incompletely folded
      states for the wild-type protein compared to its amyloidogenic variants under
      physiological conditions. These results support the concept that the ability to
      form amyloid is a generic property of proteins, but one that is mitigated against
      in a normally functioning organism.

PMID- 10940238
TI  - Amyloid fibril formation from full-length and fragments of amylin.
AB  - Amyloiddeposits of fibrillar human amylin (hA) in the pancreas may be a causative
      factor in type-2 diabetes. A detailed comparison of in vitro fibril formation by
      full-length hA(1-37) versus fragments of this peptide-hA(8-37) and hA(20-29)-is
      presented. Circular dichroism spectroscopy revealed that fibril formation was
      accompanied by a conformational change: random coil to beta-sheet/alpha-helical
      structure. Fibril morphologies were visualized by electron microscopy and
      displayed a remarkable diversity. hA(20-29) formed flat ribbons consisting of
      numerous 3. 6-nm-wide protofibrils. In contrast, hA(1-37) and hA(8-37) formed
      polymorphic higher order fibrils by lateral association and/or coiling together
      of 5.0-nm-wide protofibril subunits. For full-length hA(1-37), the predominant
      fibril type contained three protofibrils and for hA(8-37), the predominant type
      contained two protofibrils. Polymerization was also monitored with the thioflavin
      T binding assay, which revealed different kinetics of assembly for hA(1-37) and
      hA(8-37) fibrils. hA(20-29) fibrils did not bind thioflavin-T. Together the
      results demonstrate that the N-terminal region of the hA peptide influences the
      relative frequencies of the various higher order fibril types and thereby the
      overall kinetics of fibril formation. Furthermore, while residues 20-29
      contribute to the fibrils' beta-sheet core, the flanking C- and N-terminal
      regions of the hA peptide determine the interactions involved in the formation of
      higher order coiled polymorphic superstructures.

PMID- 10940239
TI  - Betabellins 15D and 16D, de Novo designed beta-sandwich proteins that have
      amyloidogenic properties.
AB  - The betabellin structure is a de novo designed beta-sandwich protein consisting
      of two 32-residue beta-sheets packed against one another by hydrophobic
      interactions. d-Amino acid residues are used to energetically favor formation of
      type-I' beta turns. Air oxidation of betabellin 15S (B15S)
      (HSLTAKIpkLTFSIAphTYTCAVpkYTAKVSH, where p denotes d-Pro, h denotes d-His, and k
      denotes d-Lys) yields betabellin 15D (B15D), a 64-residue disulfide-bridged
      protein. The amino acid sequence of B15D contains a conformationally constrained
      d-Pro residue at the i + 1 position of each type-I' beta turn. To test whether d
      Pro residues are necessary for folding at these positions, the six d-Pro residues
      of B15D are replaced by d-Ala residues in betabellin 16D (B16D). Previously,
      transmission electron microscopy showed that B15D forms unbranched, 35-A wide
      fibrils that associate into bundles in 5.0 mM 3-(N-morpholino)propanesulfonate
      and 250 mM NaCl at pH 7; under these conditions, B16D forms ribbon-like
      assemblies. The B15D fibrils resemble the protofilaments that constitute amyloid
      fibrils. The present studies show that both B15D and B16D have characteristics of
      amyloidogenic proteins: the unbranched fibrils and ribbons stained with Congo red
      and displayed a green birefringence, exhibited a cross-beta structure, and bound
      1-anilino-8-naphthalenesulfonate. Thus, these de novo designed beta-sandwich
      proteins should provide useful models for studying the mechanism of amyloid
      protofilament formation and assembly into amyloid fibrils and for designing
      potential inhibitors of amyloidogenesis.

PMID- 10940241
TI  - Measuring the forces that control protein interactions.
AB  - Although the force fields and interaction energies that control protein behavior
      can be inferred indirectly from equilibrium and kinetic measurements, recent
      developments have made it possible to quantify directly (a) the ranges,
      magnitudes, and time dependence of the interaction energies and forces between
      biological materials; (b) the mechanical properties of isolated proteins; and (c)
      the strength of single receptor-ligand bonds. This review describes recent
      results obtained by using the atomic force microscope, optical tweezers, the
      surface force apparatus, and micropipette aspiration to quantify short-range
      protein-ligand interactions and the long-range, nonspecific forces that together
      control protein behavior. The examples presented illustrate the power of force
      measurements to quantify directly the force fields and energies that control
      protein behavior.

PMID- 10940240
TI  - Criteria air pollutants and toxic air pollutants.
AB  - This review presents a brief overview of the health effects and exposures of two
      criteria pollutants--ozone and particulate matter--and two toxic air pollutants-
      benzene and formaldehyde. These pollutants were selected from the six criteria
      pollutants and from the 189 toxic air pollutants on the basis of their prevalence
      in the United States, their physicochemical behavior, and the magnitude of their
      potential health threat. The health effects data included in this review
      primarily include results from epidemiologic studies; however, some findings from
      animal studies are also discussed when no other information is available. Health
      effects findings for each pollutant are related in this review to corresponding
      information about outdoor, indoor, and personal exposures and pollutant sources.

PMID- 10940242
TI  - Structure and function of lipid-DNA complexes for gene delivery.
AB  - Owing to the rapid development of in vivo applications for nonviral gene delivery
      vectors, it is necessary to have a better understanding of how the structure
      activity relationships of these lipid-DNA complexes are affected by their
      environment. Indeed, research in gene therapy first focused on in vitro cell
      culture studies to determine the mechanisms involved in the delivery of DNA into
      the cell. New biophysical techniques such as electron microscopy and X-ray
      diffraction have been developed to discern the structure of the lipid-DNA
      complex. However, further studies have revealed discrepancies between optimal
      lipid-DNA formulations for in vitro transfection and for in vivo administration
      of these vectors. Furthermore, some immune stimulatory effects have been
      associated with in vivo lipid-DNA administration. This review summarizes the
      current state of knowledge on in vitro and in vivo lipid-DNA complex
      transfections. New prospects of vectors for in vivo gene transfer are also
      discussed.

PMID- 10940243
TI  - Signaling and subcellular targeting by membrane-binding domains.
AB  - Protein kinase C homology-1 and -2, FYVE, and pleckstrin homology domains are
      ubiquitous in eukaryotic signal transduction and membrane-trafficking proteins.
      These domains regulate subcellular localization and protein function by binding
      to lipid ligands embedded in cell membranes. Structural and biochemical analysis
      of these domains has shown that their molecular mechanisms of membrane binding
      depend on a combination of specific and nonspecific interactions with membrane
      lipids. In vivo studies of green fluorescent protein fusions have highlighted the
      key roles of these domains in regulating protein localization to plasma and
      internal membranes in cells.

PMID- 10940245
TI  - Structural symmetry and protein function.
AB  - The majority of soluble and membrane-bound proteins in modern cells are
      symmetrical oligomeric complexes with two or more subunits. The evolutionary
      selection of symmetrical oligomeric complexes is driven by functional, genetic,
      and physicochemical needs. Large proteins are selected for specific morphological
      functions, such as formation of rings, containers, and filaments, and for
      cooperative functions, such as allosteric regulation and multivalent binding.
      Large proteins are also more stable against denaturation and have a reduced
      surface area exposed to solvent when compared with many individual, smaller
      proteins. Large proteins are constructed as oligomers for reasons of error
      control in synthesis, coding efficiency, and regulation of assembly. Symmetrical
      oligomers are favored because of stability and finite control of assembly.
      Several functions limit symmetry, such as interaction with DNA or membranes, and
      directional motion. Symmetry is broken or modified in many forms: quasisymmetry,
      in which identical subunits adopt similar but different conformations;
      pleomorphism, in which identical subunits form different complexes;
      pseudosymmetry, in which different molecules form approximately symmetrical
      complexes; and symmetry mismatch, in which oligomers of different symmetries
      interact along their respective symmetry axes. Asymmetry is also observed at
      several levels. Nearly all complexes show local asymmetry at the level of side
      chain conformation. Several complexes have reciprocating mechanisms in which the
      complex is asymmetric, but, over time, all subunits cycle through the same set of
      conformations. Global asymmetry is only rarely observed. Evolution of oligomeric
      complexes may favor the formation of dimers over complexes with higher cyclic
      symmetry, through a mechanism of prepositioned pairs of interacting residues.
      However, examples have been found for all of the crystallographic point groups,
      demonstrating that functional need can drive the evolution of any symmetry.

PMID- 10940244
TI  - GCN5-related N-acetyltransferases: a structural overview.
AB  - Hundreds of acetyltransferases exist. All use a common acetyl donor--acetyl
      coenzyme A--and each exhibits remarkable specificity for acetyl acceptors, which
      include small molecules and proteins. Analysis of the primary sequences of these
      enzymes indicates that they can be sorted into several superfamilies. This review
      covers the three-dimensional structures of members of one of these superfamilies,
      now referred to in the literature as the GCN5-related N-acetyltransferases
      (GNAT), reflecting the importance of one functional category, the histone
      acetyltransferases. Despite the diversity of substrate specificities, members of
      the GNAT superfamily demonstrate remarkable similarity in protein topology and
      mode of acetyl coenzyme A binding, likely reflecting a conserved catalytic
      mechanism.

PMID- 10940246
TI  - Electrokinetically controlled microfluidic analysis systems.
AB  - Electrokinetic forces are emerging as a powerful means to drive microfluidic
      systems with flow channel cross-sectional dimensions in the tens of micrometers
      and flow rates in the nanoliter per second range. These systems provide many
      advantages such as improved analysis speed, improved reproducibility, greatly
      reduced reagent consumption, and the ability to perform multiple operations in an
      integrated fashion. Planar microfabrication methods are used to make these
      analysis chips in materials such as glass or polymers. Many applications of this
      technology have been demonstrated, such as DNA separations, enzyme assays,
      immunoassays, and PCR amplification integrated with microfluidic assays. Further
      development of this technology is expected to yield higher levels of
      functionality of sample throughput on a single microfluidic analysis chip.

PMID- 10940247
TI  - DNA recognition by Cys2His2 zinc finger proteins.
AB  - Cys2His2 zinc fingers are one of the most common DNA-binding motifs found in
      eukaryotic transcription factors. These proteins typically contain several
      fingers that make tandem contacts along the DNA. Each finger has a conserved beta
      beta alpha structure, and amino acids on the surface of the alpha-helix contact
      bases in the major groove. This simple, modular structure of zinc finger
      proteins, and the wide variety of DNA sequences they can recognize, make them an
      attractive framework for attempts to design novel DNA-binding proteins. Several
      studies have selected fingers with new specificities, and there clearly are
      recurring patterns in the observed side chain-base interactions. However, the
      structural details of recognition are intricate enough that there are no general
      rules (a "recognition code") that would allow the design of an optimal protein
      for any desired target site. Construction of multifinger proteins is also
      complicated by interactions between neighboring fingers and the effect of the
      intervening linker. This review analyzes DNA recognition by Cys2His2 zinc fingers
      and summarizes progress in generating proteins with novel specificities from
      fingers selected by phage display.

PMID- 10940248
TI  - Protein folding intermediates and pathways studied by hydrogen exchange.
AB  - In order to solve the immensely difficult protein-folding problem, it will be
      necessary to characterize the barriers that slow folding and the intermediate
      structures that promote it. Although protein-folding intermediates are not
      accessible to the usual structural studies, hydrogen exchange (HX) methods have
      been able to detect and characterize intermediates in both kinetic and
      equilibrium modes--as transient kinetic folding intermediates on a subsecond time
      scale, as labile equilibrium molten globule intermediates under destabilizing
      conditions, and as infinitesimally populated intermediates in the high free
      energy folding landscape under native conditions. Available results consistently
      indicate that protein-folding landscapes are dominated by a small number of
      discrete, metastable, native-like partially unfolded forms (PUFs). The PUFs
      appear to be produced, one from another, by the unfolding and refolding of the
      protein's intrinsically cooperative secondary structural elements, which can
      spontaneously create stepwise unfolding and refolding pathways. Kinetic
      experiments identify three kinds of barrier processes: (a) an initial intrinsic
      search-nucleation-collapse process that prepares the chain for intermediate
      formation by pinning it into a condensed coarsely native-like topology; (b)
      smaller search-dependent barriers that put the secondary structural units into
      place; and (c) optional error-dependent misfold-reorganization barriers that can
      cause slow folding, intermediate accumulation, and folding heterogeneity. These
      conclusions provide a coherent explanation for the grossly disparate folding
      behavior of different globular proteins in terms of distinct folding pathways.

PMID- 10940249
TI  - Quantitative chemical analysis of single cells.
AB  - A fundamental perspective can be achieved by targeting single cells for analysis
      with the goal of deconvoluting complex biological functions. However, single-cell
      studies have their own difficulties, such as minute volumes and sample amounts.
      Quantitative chemical analysis of single cells has emerged as a powerful new area
      in recent years due to several technological advancements. The development of
      microelectrodes has allowed the measurement of redox-active species as a function
      of cellular dynamics. This miniaturization trend is also evident in the
      separation sciences with the application of small column separations to single
      cells. Desorption ionization methods with mass spectrometric detection have shown
      single-cell capability owing to numerous technological developments. Finally,
      fluorescence imaging has also progressed to the point where single-cell dynamics
      can be probed by native fluorescence utilizing either single or multiple photon
      excitation. The results of these studies are reviewed with an emphasis on the
      quantitation of single-cell dynamics.

PMID- 10940250
TI  - The structural biology of molecular recognition by vancomycin.
AB  - Vancomycin is the archetype among naturally occurring compounds known as
      glycopeptide antibiotics. Because it is a vital therapeutic agent used world-wide
      for the treatment of infections with gram-positive bacteria, emerging bacterial
      resistance to vancomycin is a major public health threat. Recent investigations
      into the mechanisms of action of glycopeptide antibiotics are driven by a need to
      understand their detailed mechanism of action so that new agents can be developed
      to overcome resistance. These investigations have revealed that glycopeptide
      antibiotics exhibit a rich array of complex cooperative phenomena when they bind
      target ligands, making them valuable model systems for the study of molecular
      recognition.

PMID- 10940251
TI  - Comparative protein structure modeling of genes and genomes.
AB  - Comparative modeling predicts the three-dimensional structure of a given protein
      sequence (target) based primarily on its alignment to one or more proteins of
      known structure (templates). The prediction process consists of fold assignment,
      target-template alignment, model building, and model evaluation. The number of
      protein sequences that can be modeled and the accuracy of the predictions are
      increasing steadily because of the growth in the number of known protein
      structures and because of the improvements in the modeling software. Further
      advances are necessary in recognizing weak sequence-structure similarities,
      aligning sequences with structures, modeling of rigid body shifts, distortions,
      loops and side chains, as well as detecting errors in a model. Despite these
      problems, it is currently possible to model with useful accuracy significant
      parts of approximately one third of all known protein sequences. The use of
      individual comparative models in biology is already rewarding and increasingly
      widespread. A major new challenge for comparative modeling is the integration of
      it with the torrents of data from genome sequencing projects as well as from
      functional and structural genomics. In particular, there is a need to develop an
      automated, rapid, robust, sensitive, and accurate comparative modeling pipeline
      applicable to whole genomes. Such large-scale modeling is likely to encourage new
      kinds of applications for the many resulting models, based on their large number
      and completeness at the level of the family, organism, or functional network.

PMID- 10940252
TI  - Fast kinetics and mechanisms in protein folding.
AB  - This review describes how kinetic experiments using techniques with dramatically
      improved time resolution have contributed to understanding mechanisms in protein
      folding. Optical triggering with nanosecond laser pulses has made it possible to
      study the fastest-folding proteins as well as fundamental processes in folding
      for the first time. These include formation of alpha-helices, beta-sheets, and
      contacts between residues distant in sequence, as well as overall collapse of the
      polypeptide chain. Improvements in the time resolution of mixing experiments and
      the use of dynamic nuclear magnetic resonance methods have also allowed kinetic
      studies of proteins that fold too fast (greater than approximately 10(3) s-1) to
      be observed by conventional methods. Simple statistical mechanical models have
      been extremely useful in interpreting the experimental results. One of the
      surprises is that models originally developed for explaining the fast kinetics of
      secondary structure formation in isolated peptides are also successful in
      calculating folding rates of single domain proteins from their native three
      dimensional structure.

PMID- 10940253
TI  - Atomic force microscopy in the study of macromolecular crystal growth.
AB  - Atomic force microscopy (AFM) has been used to study protein, nucleic acid, and
      virus crystals in situ, in their mother liquors, as they grow. From sequential
      AFM images taken at brief intervals over many hours, or even days, the mechanisms
      and kinetics of the growth process can be defined. The appearance of both two-
      and three-dimensional nuclei on crystal surfaces have been visualized, defect
      structures of crystals were clearly evident, and defect densities of crystals
      were also determined. The incorporation of a wide range of impurities, ranging in
      size from molecules to microns or larger microcrystals, and even foreign
      particles were visually recorded. From these observations and measurements, a
      more complex understanding of the detailed character of macromolecular crystals
      is emerging, one that reveals levels of complexity previously unsuspected. The
      unique features of these crystals, apparently in AFM images, undoubtedly
      influence the diffraction properties of the crystals and the quality of the
      molecular images obtained by X-ray crystallography.

PMID- 10940255
TI  - Designed sequence-specific minor groove ligands.
AB  - In the past decade, a general design for sequence-specific minor groove ligands
      has evolved, based on the natural products distamycin and netropsin. By utilizing
      a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole
      modules, new ligands can be prepared to target almost any sequence of interest
      with both high affinity and specificity. In this review we present the design
      rules with a brief history of how they evolved. The structural basis for sequence
      specific recognition is explained, together with developments that allow linking
      of recognition modules that enable targeting of long DNA sequences. Examples of
      the affinity and specificity that can be achieved with a number of variations on
      the basic design are given. Recently these molecules have been used to compete
      with proteins both in vitro and in vivo, and a brief description of the
      experimental results are given.

PMID- 10940254
TI  - A decade of CLC chloride channels: structure, mechanism, and many unsettled
      questions.
AB  - ClC-type chloride channels are ubiquitous throughout the biological world.
      Expressed in nearly every cell type, these proteins have a host of biological
      functions. With nine distinct homologues known in eukaryotes, the ClCs represent
      the only molecularly defined family of chloride channels. ClC channels exhibit
      features of molecular architecture and gating mechanisms unprecedented in other
      types of ion channels. They form two-pore homodimers, and their voltage
      dependence arises not from charged residues in the protein, but rather via
      coupling of gating to the movement of chloride ions within the pore. Because the
      functional characteristics of only a few ClC channels have been studied in
      detail, we are still learning which properties are general to the whole family.
      New approaches, including structural analyses, will be crucial to an
      understanding of ClC architecture and function.

PMID- 10940256
TI  - Pulsed and parallel-polarization EPR characterization of the photosystem II
      oxygen-evolving complex.
AB  - Photosystem II uses visible light to drive the oxidation of water, resulting in
      bioactivated electrons and protons, with the production of molecular oxygen as a
      byproduct. This water-splitting reaction is carried out by a manganese
      cluster/tyrosine radial ensemble, the oxygen -evolving complex. Although
      conventional continuous-wave, perpendicular -polarization electron paramagnetic
      resonance (EPR) spectroscopy has significantly advanced our knowledge of the
      structure and function of the oxygen-evolving complex, significant additional
      information can be obtained with the application of additional EPR methodologies.
      Specifically, parallel-polarization EPR spectroscopy can be use to obtain highly
      resolved EPR spectra of integer spin Mn species, and pulsed EPR spectroscopy with
      electron spin echo-based sequences, such as electron spin echo envelope
      modulation and electron spin echo-electron nuclear double resonance, can be used
      to measure weak interactions obscured in continuous-wave spectroscopy by
      inhomogeneous broadening.

PMID- 10940257
TI  - Electrostatic mechanisms of DNA deformation.
AB  - The genomes of higher cells consist of double-helical DNA, a densely charged
      polyelectrolyte of immense length. The intrinsic physical properties of DNA, as
      well as the properties of its complexes with proteins and ions, are therefore of
      fundamental interest in understanding the functions of DNA as an informational
      macromolecule. Because individual DNA molecules often exceed 1 cm in length, it
      is clear that DNA bending, folding, and interaction with nuclear proteins are
      necessary for packaging genomes in small volumes and for integrating the
      nucleotide sequence information that guides genetic readout. This review first
      focuses on recent experiments exploring how the shape of the densely charged DNA
      polymer and asymmetries in its surrounding counterion distribution mutually
      influence one another. Attention is then turned to experiments seeking to
      discover the degree to which asymmetric phosphate neutralization can lead to DNA
      bending in protein-DNA complexes. It is argued that electrostatic effects play
      crucial roles in the intrinsic, sequence-dependent shape of DNA and in DNA shapes
      induced by protein binding.

PMID- 10940258
TI  - Stress-induced structural transitions in DNA and proteins.
AB  - The ability to manipulate, stretch and twist biomolecules opens the way to an
      understanding of their structural transitions. We review some of the recently
      discovered stress-induced structural transitions in DNA as well as the
      application of single molecule manipulation techniques to DNA unzipping and to
      the study of protein folding/unfolding transitions.

PMID- 10940259
TI  - Molecular mechanisms controlling actin filament dynamics in nonmuscle cells.
AB  - We review how motile cells regulate actin filament assembly at their leading
      edge. Activation of cell surface receptors generates signals (including activated
      Rho family GTPases) that converge on integrating proteins of the WASp family
      (WASp, N-WASP, and Scar/WAVE). WASP family proteins stimulate Arp2/3 complex to
      nucleate actin filaments, which grow at a fixed 70 degrees angle from the side of
      pre-existing actin filaments. These filaments push the membrane forward as they
      grow at their barbed ends. Arp2/3 complex is incorporated into the network, and
      new filaments are capped rapidly, so that activated Arp2/3 complex must be
      supplied continuously to keep the network growing. Hydrolysis of ATP bound to
      polymerized actin followed by phosphate dissociation marks older filaments for
      depolymerization by ADF/cofilins. Profilin catalyzes exchange of ADP for ATP,
      recycling actin back to a pool of unpolymerized monomers bound to profilin and
      thymosin-beta 4 that is poised for rapid elongation of new barbed ends.

PMID- 10940260
TI  - Unnatural ligands for engineered proteins: new tools for chemical genetics.
AB  - Small molecules that modulate the activity of biological signaling molecules can
      be powerful probes of signal transduction pathways. Highly specific molecules
      with high affinity are difficult to identify because of the conserved nature of
      many protein active sites. A newly developed approach to discovery of such small
      molecules that relies on protein engineering and chemical synthesis has yielded
      powerful tools for the study of a wide variety of proteins involved in signal
      transduction (G-proteins, protein kinases, 7-transmembrane receptors, nuclear
      hormone receptors, and others). Such chemical genetic tools combine the
      advantages of traditional genetics and the unparalleled temporal control over
      protein function afforded by small molecule inhibitors/activators that act at
      diffusion controlled rates with targets.

PMID- 10940261
TI  - Pancreas divisum: opinio divisa.

PMID- 10940263
TI  - Distension in non-consulting dyspeptics: a swell idea.

PMID- 10940264
TI  - Suicide and the not-so-innocent bystander.

PMID- 10940262
TI  - COX-1 and COX-2 products in the gut: therapeutic impact of COX-2 inhibitors.

PMID- 10940265
TI  - Dissecting out crytogenic liver disease.

PMID- 10940266
TI  - CagA: a role at last.

PMID- 10940267
TI  - Differences in gastric mechanosensory function after repeated ramp distensions in
      non-consulters with dyspepsia and healthy controls.
AB  - BACKGROUND: Abnormal visceral mechano-sensory function has been reported in 50%
      of non-ulcer (functional) dyspepsia patients. However, only a minority of
      subjects with functional dyspepsia ever seek medical attention. Whether factors
      promoting health care seeking behaviour explain visceral hypersensitivity is
      unknown. Decreased rectal thresholds following sigmoid mechanical stimulation
      have been observed in irritable bowel but this mechanism has not been evaluated
      in functional dyspepsia. AIMS: To compare visceral mechanosensory function in
      healthy asymptomatic subjects and non-consulters with chronic unexplained
      dyspepsia. METHODS: Forty two volunteers were recruited: 10 had a history of
      chronic or recurrent upper abdominal pain or discomfort as assessed by a
      standardised questionnaire, and Helicobacter pylori status was determined (ELISA
      and (13)C urea breath test). Eight H pylori negative, currently asymptomatic
      dyspeptic subjects who were non-consulters and eight asymptomatic age and sex
      matched H pylori negative controls were enrolled. With a barostat bag in the
      proximal part of the stomach, visceral perception thresholds were determined by
      random tracking. Thereafter, standardised ramp distensions were performed (2 mm
      Hg increments, duration of each pressure step 30 seconds, maximum pressure 35 mm
      Hg (or occurrence of pain)) and tracking of sensory thresholds and ramp
      distension repeated every 30 minutes for a total of two hours. RESULTS: Overall,
      thresholds for first perception were significantly lower in dyspeptic subjects
      compared with asymptomatic controls (12.5 (0.6) mm Hg v 17.5 (1.0) mm Hg;
      p<0.02). After repeated ramp distensions, thresholds for first perception
      significantly increased by 3.6 (0.7) mm Hg in healthy subjects compared with 0.1
      (1.4) mm Hg in subjects with dyspepsia (p<0.05 dyspeptics v controls).
      CONCLUSIONS: (1) Repeated mechanical stimulation increases visceral sensory
      thresholds in asymptomatic subjects while thresholds remain unchanged in
      dyspeptics. (2) Visceral hyperalgesia occurs in dyspeptic subjects who are not
      health care seekers.

PMID- 10940268
TI  - Functional assessment of beta adrenoceptor subtypes in human colonic circular and
      longitudinal (taenia coli) smooth muscle.
AB  - BACKGROUND AND AIMS: The subtype and species related heterogeneity of beta
      adrenoceptors prompted a functional reappraisal of these molecular targets of
      motility inhibition in the human colon. METHODS: Relaxation of muscle strips was
      measured in vitro. RESULTS: The following agonists had decreasing relaxing
      potency (effective concentration range 10(-8)-10(-4) mol/l): (-)isoprenaline (non
      selective), terbutaline (beta(2) selective), CGP 12177 (beta(3) selective, also
      beta(1), beta(2) antagonist), and SR 58611A (beta(3) selective). Isoprenaline and
      terbutaline were more potent on circular than taenia strips; CGP 12177 and SR
      58611A weakly and partially relaxed taenia but had little effect on circular
      strips. The potency of isoprenaline on circular strips was greatly reduced by the
      beta(1) selective antagonist CGP 20712 (10(-7) mol/l), and less so by ICI 118551
      (10(-7) mol/l, beta(2) selective). CGP 20712 and ICI 118551 together (both 3 x
      10(-6) mol/l) had no effect on taenia relaxation by SR 58611A and rendered
      isoprenaline and terbutaline virtually inactive on circular strips, although not
      on taenia, which was relaxed at higher than control concentrations and maximally
      by isoprenaline. Propranolol, a beta(1), beta(2) non-selective antagonist, at
      high concentrations (10(-5) mol/l) prevented taenia relaxation by CGP 12177 and
      SR 58611A; its quantitative antagonism of isoprenaline (in common with that of
      CGP 12177 used as an antagonist) was competitive in circular strips but not on
      taenia. CONCLUSIONS: beta(1), beta(2), and beta(3) adrenoceptors are functionally
      detectable in the human colon; agonist stimulation of any one type relaxed taenia
      but only isoprenaline was fully effective at the beta(3) subtype.

PMID- 10940269
TI  - Combined suicide and cytokine gene therapy for peritoneal carcinomatosis.
AB  - BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and
      tumours disseminated in the peritoneal cavity are suitable for in situ delivery
      of a therapeutic gene. AIMS: The efficacy of a therapy combining a suicide gene
      (herpes simplex virus type I thymidine kinase (HSV-TK)) and cytokine genes was
      investigated in a model of peritoneal carcinomatosis induced by colon carcinoma
      cells in syngeneic rats. MATERIAL AND METHODS: Pre-established macroscopic
      tumours in BDIX rats were treated by intraperitoneal injections of retrovirus
      producing cells (FLYA13 TK, FLYA13 granulocyte macrophage-colony stimulating
      factor (GM-CSF), FLYA13 interleukin 12 (IL-12)) and ganciclovir (GCV). RESULTS:
      TK/GCV treated animals showed a slight increase in survival time (72 days)
      compared with the control group (63 days) while the association of cytokine and
      TK/GCV gene therapy resulted in significantly improved survival, with a large
      proportion of animals remaining tumour free on day 480 (60% and 40% for TK/GCV/GM
      CSF and TK/GCV/IL-12 treated animals, respectively). Histological analysis of
      treated animals showed that the remaining tumour nodes were infiltrated by
      mononuclear cells but no major differences were observed between the various
      treatments. Immunohistochemical analysis revealed that lymphoid CD4(+) and CD8(+)
      T cells as well as macrophages accumulated outside untreated tumour nodes while
      CD8(+) and CD25(+) activated T cells and macrophages heavily infiltrated the
      tumours after the different treatments. CONCLUSIONS: Our data indicate that
      combined suicide and cytokine gene therapy is a powerful approach for the
      treatment of macroscopic peritoneal carcinomatosis.

PMID- 10940270
TI  - Role of fucosyltransferases in the association between apomucin and Lewis antigen
      expression in normal and malignant gastric epithelium.
AB  - BACKGROUND: In normal gastric epithelium, MUC5AC is detected in superficial
      epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral
      glands with Lewis type 2. Therefore, the stomach constitutes an excellent model
      to examine the role of glycosyltransferases in determining the specificity of
      apomucin glycosylation. AIMS: To determine the molecular basis of this
      association and to examine changes in expression of gastric and intestinal
      apomucins and their association with Lewis antigens during the gastric
      carcinogenesis process. METHODS: Fucosyltransferase (FUT1, FUT2, FUT3) and mucin
      (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase
      chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1
      and 2) expression were analysed using single and double immunohistochemistry and
      in situ hybridisation. RESULTS: In the normal stomach, FUT1 is exclusively
      detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This
      co-regulation is lost in gastric tumours, as is differential expression of MUC5AC
      and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those
      with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric
      type and intestinal-type mucins are coexpressed. These changes are early events
      in the gastric carcinogenesis process, as they are detected in intestinal
      metaplasia. CONCLUSIONS: The glycosylation pattern found in normal gastric
      epithelium is dictated by the specific set of fucosyltranferases expressed by the
      cells rather than by the apomucin sequence. The development of intestinal
      metaplasia and gastric cancer is associated with the appearance of cellular
      phenotypes that are absent from normal epithelium.

PMID- 10940271
TI  - Detection of Ki-ras gene point mutations in bile specimens for the differential
      diagnosis of malignant and benign biliary strictures.
AB  - BACKGROUND AND AIM: The present study was undertaken to determine if detection of
      Ki-ras gene point mutations in bile specimens could differentiate between benign
      and malignant biliary strictures. PATIENTS: Bile specimens were obtained from 117
      patients exhibiting a stricture of the main bile duct, the nature of which was
      assessed by cholangiography, histology, and follow up. METHODS: DNA from frozen
      bile specimens was extracted, amplified, and tested for codon 12 point mutations
      of Ki-ras gene using sequence specific oligonucleotide hybridisation and mutant
      allele specific amplification. RESULTS: DNA amplification was successful in
      110/117 bile specimens (94%). Detection of Ki-ras gene mutations in bile
      specimens was positive in 24.4% (22/90) of patients with malignant strictures, in
      31.4% (22/70) when only primary malignant tumours were considered, and in 4%
      (1/25) of patients with benign strictures. Of the 49 patients with histological
      specimens obtained before surgery, the sensitivity of histology, Ki-ras mutation
      analysis, and combined methods was 59.2%, 28.6%, and 73.5% respectively.
      CONCLUSIONS: Our study showed that Ki-ras mutations may be detected in about one
      third of bile specimens from patients with primary tumours invading the main bile
      duct. Detection of such mutations appears to be specific and may help to
      differentiate between benign and malignant biliary strictures.

PMID- 10940272
TI  - Elevated levels of the pro-carcinogenic adduct, O(6)-methylguanine, in normal DNA
      from the cancer prone regions of the large bowel.
AB  - BACKGROUND: The pro-mutagenic lesion O(6)-methyldeoxyguanosine (O(6)-MedG), a
      marker of exposure to many N-nitroso compounds (NOC), can be detected in normal
      and tumour DNA isolated from colorectal tissue. The biological significance of
      this exposure is, as yet, unknown but in situ NOC formation is bacterially
      catalysed suggesting that NOC formation and potentially DNA alkylation will vary
      throughout the large bowel. AIMS: To determine if O(6)-MedG levels in colorectal
      DNA vary within the large bowel. PATIENTS: We studied 62 men and women undergoing
      surgery for colorectal tumours in the north west of England. METHODS: O(6)-MedG
      levels were measured in paired normal and tumour DNA samples. DNA was digested to
      nucleosides, fractionated by HPLC, and purified O(6)-MedG quantified by a
      radioimmunoassay. RESULTS: O(6)-MedG was detected in 27 out of a total of 62
      (43%) normal DNA samples and in 30 of 58 (52%) tumour DNA samples: it was present
      at concentrations of <0. 01-0.94 and <0.01-0.151 micromol O(6)-MedG/mol
      deoxyguanosine for normal and tumour DNA, respectively. Levels of O(6)-MedG in
      normal, but not tumour, DNA from the proximal colon were lower than those found
      in DNA from either the sigmoid colon (p=0.03) or rectum (p=0. 05). When the
      analysis was restricted to samples that contained O(6)-MedG, similar results were
      obtained in that O(6)-MedG levels in normal DNA were lower in the proximal colon
      than in the sigmoid colon (p=0.04) or rectum (p=0.03). CONCLUSIONS: DNA
      alkylation varied within the large bowel possibly due to in situ NOC formation
      and was highest in areas of the colon and rectum where the highest incidence of
      large bowel tumours occurs, suggesting that DNA alkylation may play a role in the
      aetiology of colorectal cancer.

PMID- 10940273
TI  - IgG(1) antiendomysium and IgG antitissue transglutaminase (anti-tTG) antibodies
      in coeliac patients with selective IgA deficiency. Working Groups on Celiac
      Disease of SIGEP and Club del Tenue.
AB  - BACKGROUND: In selective IgA deficiency (IgAD), there is no reliable screening
      test for coeliac disease (CD). AIM: To evaluate the usefulness of IgG(1)
      antiendomysium and IgG antitissue transglutaminase tests for CD diagnosis in
      IgAD. METHODS: IgA and IgG antigliadin antibodies (IgA- and IgG-AGA), IgA and
      IgG(1) antiendomysium antibodies (IgA- and IgG(1)-EMA), and IgA and IgG
      antitissue transglutaminase (IgA- and IgG-anti-tTG) were assayed in: (a) 20
      untreated IgAD/CD patients; (b) 34 IgAD/CD patients on a strict gluten free diet
      (GFD); (c) 10 IgAD/CD patients not on a strict GFD; (d) 11 untreated CD patients
      without IgAD; (e) 10 healthy IgAD patients; and (f) 25 healthy controls. RESULTS:
      In all untreated IgAD/CD patients, IgG(1)-EMA, IgG-anti-tTG, and IgG-AGA were
      positive whereas IgA antibodies against these antigens were negative. IgAD/CD
      patients on a strict GFD did not produce IgG-AGA or IgG(1)-EMA but four of 34
      produced IgG anti-tTG. IgAD/CD subjects not on a strict GFD produced IgG-AGA
      whereas 5/10 and 4/10 were IgG(1)- EMA and IgG-anti-tTG negative, respectively.
      Untreated CD patients without IgAD were AGA (IgA and IgG), EMA (IgA and IgG(1)),
      and anti-tTG (IgA and IgG) positive. Healthy controls were AGA and EMA negative
      whereas two of 10 apparently healthy IgAD subjects and one of 25 healthy negative
      control were IgG-anti-tTG positive. CONCLUSIONS: Both IgG(1)-EMA and IgG-anti-tTG
      tests appear to be useful for identification of IgAD/CD patients whereas they are
      less satisfactory for monitoring dietary compliance in these subjects. In
      addition, our findings seem to suggest that IgG-EMA autoantibodies produced by
      coeliac patients are mainly of the IgG(1) subtype.

PMID- 10940274
TI  - Elevated plasma glucagon-like peptide 1 and 2 concentrations in ileum resected
      short bowel patients with a preserved colon.
AB  - BACKGROUND: The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially
      from L cells located mainly in the ileum. Both hormones prolong intestinal
      transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy
      have poor adaptation, rapid gastric and intestinal transit, and impaired
      postprandial GLP-2 secretion. Ileum resected short bowel patients with a
      preserved colon show evidence of functional adaptation and have normal gastric
      emptying. AIM: To investigate if GLP-1 and GLP-2 contribute to the positive
      effects of a preserved colon in short bowel patients by measuring circulating
      levels of GLP-1 and GLP-2 in seven ileum resected short bowel patients with a
      preserved colon and seven age and sex matched controls. METHODS: GLP-1 and GLP-2
      immunoreactivity was measured by specific radioimmunoassays in plasma collected
      at fasting and at regular intervals 180 minutes after a test meal. RESULTS:
      Median (25-75%) fasting GLP-2 values were 72 (69-105) pmol/l versus 23 (19-27)
      pmol/l (p=0.001) and meal stimulated area under the curve was 21 078 (14 811-26
      610) min x pmol/l versus 11 150 (7151-12 801) min x pmol/l (p=0.01) in short
      bowel patients with a preserved colon compared with control subjects. Fasting GLP
      1 values were 10 (6-12) pmol/l versus 5 (3-5) pmol/l (p=0.01) and meal stimulated
      area under the curve was 3418 (2966-6850) min x pmol/l versus 2478 (1929-3199)
      min x pmol/l (p=0.04), respectively. CONCLUSION: Ileum resected short bowel
      patients with a preserved colon had elevated fasting plasma concentrations of GLP
      1 and GLP-2 and significantly larger meal stimulated areas under the curve
      compared with age and sex matched controls. Elevated GLP-1 and GLP-2
      concentrations may contribute to the positive effects of a preserved colon on
      intestinal motility and functional adaptation in ileum resected short bowel
      patients.

PMID- 10940275
TI  - Enterohaemorrhagic Escherichia coli O157:H7 target Peyer's patches in humans and
      cause attaching/effacing lesions in both human and bovine intestine.
AB  - BACKGROUND: Enterohaemorrhagic Escherichia coli (EHEC) constitute a significant
      risk to human health worldwide, and infections, particularly with serogroup
      O157:H7, are associated with consumption of a variety of food and water vehicles,
      particularly food of bovine origin. EHEC cause acute gastroenteritis, bloody
      diarrhoea, and haemorrhagic colitis; up to 10% of cases develop severe
      complications, including the haemolytic uraemic syndrome, with a 5% case
      fatality. A virulence characteristic of enteropathogenic E coli, the
      attaching/effacing lesion, is considered to be important in EHEC. However,
      although EHEC produce this lesion on cultured human cells, this has not been
      demonstrated on human intestinal mucosal surfaces. In addition, the initial
      site(s) of colonisation of EHEC in humans is not known. AIMS: To assess the
      association of EHEC O157:H7 with paediatric and bovine intestine using in vitro
      organ culture and determine if attaching/effacing lesions occur. METHODS:
      Ultrastructural analysis of in vitro intestinal organ cultures of human small and
      large intestine was used to investigate adhesion of O157:H7 EHEC to intestinal
      surfaces. Bovine intestinal organ culture was used to examine the pathology
      produced by the same EHEC strain in cattle. RESULTS: The study showed that EHEC
      O157:H7 adhered to human intestinal mucosa. Binding and attaching/effacing lesion
      formation of O157:H7 in humans was restricted to follicle associated epithelium
      of Peyer's patches. The same strain caused attaching/effacing lesions on bovine
      mucosa. CONCLUSIONS: O157:H7 targets follicle associated epithelium in humans
      where it causes attaching/effacing lesions. The same human isolate can cause
      attaching/effacing lesions in cattle, indicating that similar pathogenic
      mechanisms operate across human and bovine species

PMID- 10940276
TI  - Effect of vasoactive intestinal polypeptide (VIP) antagonism on rat jejunal fluid
      and electrolyte secretion induced by cholera and Escherichia coli enterotoxins.
AB  - BACKGROUND: The enteric nervous system is important in the pathophysiology of
      intestinal fluid secretion induced by cholera toxin (CT), Escherichia coli heat
      labile (LT), and heat stable (STa) toxins. The neurotransmitters involved are not
      fully elucidated. Vasoactive intestinal polypeptide (VIP), a potent intestinal
      secretagogue present in the enteric nervous system, is increased after exposure
      of the cat intestine to CT. Whether VIP is involved in the pathogenesis of
      cholera and other toxins in not known. AIM: To study in vivo the effect of VIP
      antagonism on jejunal fluid secretion induced by CT, LT, and STa. METHODS: CT, LT
      (25 microg), or 0.9% NaCl was instilled in an isolated 25 cm segment of rat
      jejunum, and the VIP antagonist (VIPa) [4Cl-D-Phe(6), Leu(17)]-VIP (0.2 or 2
      microg/kg/min) or 0.9% NaCl was given intravenously. Two hours later, single pass
      in vivo jejunal perfusion was performed to assess fluid movement. In STa
      experiments, intravenous VIPa or 0.9% NaCl was given and 30 minutes later the
      jejunal segment was perfused with a solution containing STa 200 microg/l.
      RESULTS: VIPa had no effect on basal intestinal fluid absorption. CT induced net
      fluid secretion (median -68 microl/min/g dry intestinal weight (interquartile
      range -80 to -56)) which was dose dependently reversed by VIPa (6.2 (-16 to 34)
      and 29 (17 to 42); p<0.01). Similarly, LT induced secretion (-63 (-73 to -30))
      was attenuated by VIPa (0.2 microg/kg/min) (-15 (-24 to -1); p<0.01) and totally
      reversed to normal levels by VIPa (2 microg/kg/min) (37 (28-56); p<0. 01 compared
      with LT and not significant compared with normal controls). STa induced secretion
      (-17 (-19 to -2)) was also reversed by VIPa (12 (9-23) and 14 (0-26); p<0.01).
      CONCLUSION: VIP plays an important role in CT, LT, and STa induced intestinal
      secretion and may be the final putative neurotransmitter in the pathophysiology
      of these toxins.

PMID- 10940277
TI  - Neurokinin-1 receptor expression in inflammatory bowel disease: molecular
      quantitation and localisation.
AB  - BACKGROUND: Substantial evidence implicates the neuropeptide substance P (SP) in
      mucosal immunoinflammatory responses. Autoradiographic studies have suggested a
      disturbance in SP receptor expression in inflammatory bowel disease (IBD). AIMS:
      Because of technical limitations such as poor cellular resolution with
      autoradiography, we used molecular methods to specifically localise the cellular
      expression of the neurokinin-1 receptor (NK-1R) in IBD colon, and to quantitate
      NK-1R mRNA expression levels therein. METHODS: In situ hybridisation and
      immunohistochemistry were used to localise NK-1R mRNA and protein, respectively,
      in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections.
      NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were
      quantitated by competitive reverse transcription-polymerase chain reaction.
      RESULTS: NK-1R expression was localised to lamina propria mononuclear cells,
      epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal
      and IBD colon. No ectopic NK-1R expression was observed in IBD. However, we found
      increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant
      negative epithelial expression of NK-1R in UC, and increased expression of NK-1R
      in CD myenteric plexus. Quantitation of NK-1R mRNA expression in IBD colonic
      mucosal biopsies revealed marked upregulation of NK-1R mRNA levels compared with
      non-inflamed mucosal expression levels (p<0.01). CONCLUSIONS: This report
      demonstrates the strategic localisation and upregulation of NK-1R expression in
      IBD colon, and thereby suggests the involvement of substance P in the
      pathophysiological symptoms of IBD.

PMID- 10940278
TI  - Butyrate inhibits inflammatory responses through NFkappaB inhibition:
      implications for Crohn's disease.
AB  - BACKGROUND/AIM: Proinflammatory cytokines are key factors in the pathogenesis of
      Crohn's disease (CD). Activation of nuclear factor kappa B (NFkappaB), which is
      involved in their gene transcription, is increased in the intestinal mucosa of CD
      patients. As butyrate enemas may be beneficial in treating colonic inflammation,
      we investigated if butyrate promotes this effect by acting on proinflammatory
      cytokine expression. METHODS: Intestinal biopsy specimens, isolated lamina
      propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured
      with or without butyrate for assessment of secretion of tumour necrosis factor
      (TNF) and mRNA levels. NFkappaB p65 activation was determined by
      immunofluorescence and gene reporter experiments. Levels of NFkappaB inhibitory
      protein (IkappaBalpha) were analysed by western blotting. The in vivo efficacy of
      butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced
      colitis. RESULTS: Butyrate decreased TNF production and proinflammatory cytokine
      mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate
      abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and
      transmigration of NFkappaB from the cytoplasm to the nucleus. LPS induced
      NFkappaB transcriptional activity was decreased by butyrate while IkappaBalpha
      levels were stable. Butyrate treatment also improved TNBS induced colitis.
      CONCLUSIONS: Butyrate decreases proinflammatory cytokine expression via
      inhibition of NFkappaB activation and IkappaBalpha degradation. These anti
      inflammatory properties provide a rationale for assessing butyrate in the
      treatment of CD.

PMID- 10940279
TI  - A reproducible grading scale for histological assessment of inflammation in
      ulcerative colitis.
AB  - BACKGROUND: Evaluation of histological activity in ulcerative colitis needs to be
      reproducible but has rarely been tested. This could be useful both clinically and
      in clinical trials. AIM: To develop reproducible criteria which are valid in the
      assessment of acute inflammation (activity) and chronicity, and to evaluate these
      features in an interobserver variability study. METHODS: A six grade
      classification system for inflammation was developed which could also be fine
      tuned within each grade. The grades were: 0, structural change only; 1, chronic
      inflammation; 2, lamina propria neutrophils; 3, neutrophils in epithelium; 4,
      crypt destruction; and 5, erosions or ulcers. Ninety nine haematoxylin-eosin
      sections from endoscopically inflamed and non-inflamed mucosa from patients with
      distal ulcerative colitis were assessed in two separate readings by three
      pathologists independently and without knowledge of the clinical status.
      Interobserver agreement was compared pairwise using kappa statistics. RESULTS:
      Initially, kappa values between the observers were 0.20, 0.42, and 0.26, which
      are too low to be of value. Following development of a semiquantitative pictorial
      scale for each criterion, kappa values improved to 0.62, 0.70, and 0.59. For
      activity defined by neutrophils between epithelial cells, kappa values were
      0.903, 1.000, and 0.907. Complete agreement was reached in 64% of samples of
      endoscopically normal and in 66% of endoscopically inflamed tissue. Neutrophils
      in epithelium correlated with the presence of crypt destruction and ulceration.
      CONCLUSION: A histological activity system was developed for ulcerative colitis
      that showed good reproducibility and modest agreement with the endoscopic grading
      system which it complemented. It has potential value both clinically and in
      clinical trials.

PMID- 10940281
TI  - Comparable expression of matrix metalloproteinases 1 and 2 in pouchitis and
      ulcerative colitis.
AB  - BACKGROUND AND AIMS: Matrix metalloproteinases (MMPs) are implicated in the
      tissue destruction associated with inflammatory diseases. Proctocolectomy with
      ileo-anal pouch (IAP) anastomosis is associated with pouchitis, particularly in
      patients with ulcerative colitis (UC). The aim of this study was to quantify MMP
      1 and MMP-2 in inflamed and uninflamed pouches of patients with UC compared with
      those with active UC. IAP patients with familial adenomatous polyposis (FAP)
      served as controls. METHODS: Biopsies were taken from 33 patients with IAP (UC,
      n=25; FAP, n=8) and from 10 UC patients. MMP-1 and MMP-2 were quantified using
      sandwich enzyme linked immunosorbent assays. In addition, northern and western
      blotting and in situ hybridisation experiments were performed. RESULTS: In
      pouchitis (n=11), MMP-1 and MMP-2 concentrations were increased compared with
      uninflamed pouches of patients with UC (n=14) or FAP (n=8) (MMP-1 17.7 ng/mg
      protein v 7.8 (UC) v 7.6 (FAP), p</=0.05; MMP-2 16.4 v 9.5 (UC) v 6.3 (FAP),
      p</=0.05). Western and northern blots revealed increased MMP-1 and MMP-2 protein
      and transcript concentrations in inflamed pouches. Mesenchymal cells were
      identified as major producers of MMP-1 and MMP-2 in pouchitis. A similar increase
      in MMPs was observed in tissues of patients with active UC. CONCLUSIONS: Our
      results support the hypothesis that MMPs are involved in mucosal destruction and
      crypt hyperplasia, as seen in pouchitis.

PMID- 10940280
TI  - Mucosal 5-aminosalicylic acid concentration inversely correlates with severity of
      colonic inflammation in patients with ulcerative colitis.
AB  - BACKGROUND AND AIM: The treatment of ulcerative colitis (UC) with 5
      aminosalicylic acid (5-ASA) does not have the same therapeutic effect in all
      patients. We tested the hypothesis that the effectiveness of the drug is related
      to its mucosal concentration. PATIENTS: Twenty one UC patients receiving oral 5
      ASA (2.4-3.2 g/day) were enrolled in the study. Four were also receiving topical
      treatment (2 g/day). METHODS: Six endoscopic biopsies were taken from the rectum
      for measurement of 5-ASA concentrations (ng/mg) by HPLC; soluble interleukin 2
      receptor (sIL-2R) concentrations (U/ml) were measured by ELISA and histology.
      Endoscopic and histological appearance was graded on a four point scale (0-3).
      The Wilcoxon's rank test and Pearson's correlation coefficient were used for
      statistical analysis. RESULTS: Mucosal concentrations of 5-ASA were significantly
      higher (p=0.03) in patients with endoscopic scores of 0-1 compared with those
      with scores of 2-3 (16.1 (range 10.2-45) v 5. 5 (3.5-17.4), respectively) and in
      patients with lower histological inflammation compared with those with more
      severe scores (17.4 (10. 5-45) v 8.9 (3.5-17.2), respectively) (p<0.01). In
      contrast, mucosal sIL2-R concentrations were significantly lower in patients with
      slight endoscopic and histological lesions than in those with more severe
      disease. A significative inverse correlation (r=-0.85) was found between 5-ASA
      and sIL-2R mucosal concentrations (p=0.00008). CONCLUSIONS: In patients with UC,
      in the same area of the intestinal tract, we found that the higher the 5-ASA
      mucosal concentrations, the lower the IL-2R levels and endoscopic and
      histological scores. We hypothesise that maintenance of high mucosal 5-ASA
      concentrations in all colonic segments could contribute to improve clinical
      outcome in UC patients.

PMID- 10940282
TI  - Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis.
AB  - BACKGROUND: Changes in substance P content and a relationship between the degree
      of perineural inflammation and pain has been demonstrated in chronic
      pancreatitis. Whether a relationship exists between neural alteration and
      pancreatic inflammation (neurogenic inflammation) is not known. AIMS: In the
      present study we evaluated gene expression of preprotachykinin A (PPT-A), the
      gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic
      mediator whose release is co-regulated by substance P. PATIENTS: Pancreatic
      tissue specimens obtained from 21 patients (16 male, five female) with chronic
      pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed.
      METHODS: Gene expression of PPT-A and interleukin 8 was studied by northern blot
      analysis. Respective proteins were localised using immunohistochemistry. RESULTS:
      Northern blot analysis showed that PTT-A mRNA expression levels were present at
      comparable levels in normal and chronic pancreatitis tissue samples. In contrast,
      interleukin 8 mRNA was expressed at very low levels in normal controls but was
      increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using
      immunohistochemistry, interleukin 8 protein was localised mainly in immune cells
      often found around enlarged pancreatic nerves. In addition, in chronic
      pancreatitis, intense interleukin 8 immunostaining was present in metaplastic
      ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis
      samples there was a positive relationship between interleukin 8 mRNA levels and
      the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score
      (r=0.713; p<0.001). CONCLUSIONS: Our data indicate that in chronic pancreatitis,
      the increase in substance P in enlarged pancreatic nerves is not caused by
      enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of
      substance P synthesis is outside of the pancreas. In addition, localisation of
      interleukin 8 positive immune cells around pancreatic nerves further supports the
      existence of neuroimmune interactions as a pathophysiological mechanism in
      chronic pancreatitis.

PMID- 10940284
TI  - Topical tacrolimus may be effective in the treatment of oral and perineal Crohn's
      disease.
AB  - BACKGROUND: Crohn's disease of the mouth or perineum is more common in young
      people, and notably resistant to treatment. However, there is increasing evidence
      that topical therapy with tacrolimus (FK506) may be effective in skin diseases
      resistant to cyclosporin because of its high uptake in inflamed skin and
      subsequent reduction in keratinocyte chemokine production. PATIENTS AND METHODS:
      Tacrolimus ointment was made up inhouse from the intravenous or oral formulation
      and suspended in appropriate vehicles for perioral or perianal administration at
      an initial concentration of 0.5 mg/g. This was administered open label to eight
      children (aged 5-18 years) with treatment resistant oral (three patients) and/or
      ulcerating perineal (six patients) Crohn's disease. RESULTS: Marked improvement
      was seen in 7/8 patients within six weeks and healing within 1-6 months. One
      child with gross perineal and colonic disease showed little response. Two of the
      responders showed rebound worsening when tacrolimus was stopped or the dosage
      reduced rapidly, and one of these eventually required proctectomy. Slower weaning
      of drug concentration has been successful in 6/8 patients, with four receiving
      intermittent treatment and two on regular reduced dosage (0.1-0.3 mg/g) with
      follow up times of six months to 3.5 years. Serum concentrations of tacrolimus
      were undetectable in all patients. CONCLUSIONS: Topical tacrolimus at low
      concentrations (0.5 mg/g) shows promise in the management of childhood perineal
      and oral Crohn's disease, with no evidence of significant systemic absorption.
      However, rapid weaning or abrupt cessation of therapy may cause rebound worsening
      of disease. Further controlled studies are required to assess the efficacy and
      safety of this treatment.

PMID- 10940283
TI  - Pathological and virological findings in patients with persistent
      hypertransaminasaemia of unknown aetiology.
AB  - BACKGROUND: The histopathological spectrum and role of hepatitis viruses in cases
      of hypertransaminasaemia of unknown aetiology have not been correctly analysed in
      a sufficiently large number of patients. METHODS: We studied 1075 consecutive
      patients referred for liver biopsy because of elevation of alanine
      aminotransferase (ALT) levels for more than six months. From this population we
      selected those cases in whom the aetiology could not be defined from clinical,
      biochemical, and serological data obtained before biopsy. In these patients liver
      biopsies were reviewed, and hepatitis B virus (HBV)-DNA and hepatitis C virus
      (HCV)-RNA were assayed in serum by polymerase chain reaction (PCR). Serum
      hepatitis G virus (HGV)-RNA was determined by PCR in 74 patients. RESULTS: Of
      1075 patients studied, the cause of the increased serum ALT levels remained
      elusive after appropriate testing in 109 patients (10.1%). Liver biopsies from
      these patients showed non-specific changes in 32.7% of cases, non-alcoholic
      steatohepatitis (NASH) in 15.8%, and chronic hepatitis or cirrhosis in 51.5%. HBV
      DNA and/or HCV-RNA was detected more frequently in cryptogenic liver disease than
      in healthy blood donors (26.7% v 3.4%; p<0.001). HGV-RNA was found in only one
      patient. The proportion of cases with detectable HBV-DNA or HCV-RNA was 14.3% in
      patients with non-specific changes or NASH, 30.7% in patients with chronic
      hepatitis, and 61.5% in patients with cirrhosis. Cirrhosis was found more
      frequently in patients with positive HBV-DNA and/or HCV-RNA in serum than in
      those who tested negatively (p=0.005). CONCLUSIONS: In our series, patients in
      whom biochemical and serological data did not determine the aetiology of the
      disease represented 10% of all cases referred for liver biopsy for persistent
      elevation of serum transaminases. Approximately 50% of patients had chronic
      hepatitis or cirrhosis and the remainder had NASH or non-specific changes. Occult
      viral infections were found in a high proportion of cases in the first group and
      in a low percentage of patients in the second.

PMID- 10940285
TI  - Effect on outcome of the lengthening waiting list for liver transplantation.

PMID- 10940292
TI  - Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf
      1.
AB  - We report here the biochemical analysis of the reconstituted de novo procaspase-9
      activation using highly purified cytochrome c, recombinant apoptotic protease
      activating factor-1 (Apaf-1), and recombinant procaspase-9. Using a nucleotide
      binding assay, we found that Apaf-1 alone bound dATP poorly and the nucleotide
      binding to Apaf-1 was significantly stimulated by cytochrome c. The binding of
      dATP to Apaf-1 induces the formation of a multimeric Apaf-1. cytochrome c
      complex, apoptosome. Procaspase-9 also synergistically promotes dATP binding to
      Apaf-1 in a cytochrome c-dependent manner. The dATP bound to apoptosome remained
      as dATP, not dADP. A nonhydrolyzable ATP analog, ADPCP (beta,gamma-methylene
      adenosine 5'-triphosphate), was able to support apoptosome formation and caspase
      activation in place of dATP or ATP. These data indicate that the key event in
      Apaf-1-mediated caspase-9 activation is cytochrome c-induced dATP binding to Apaf
      1.

PMID- 10940293
TI  - Structural and genomic correlates of hyperthermostability.
AB  - While most organisms grow at temperatures ranging between 20 and 50 degrees C,
      many archaea and a few bacteria have been found capable of withstanding
      temperatures close to 100 degrees C, or beyond, such as Pyrococcus or Aquifex.
      Here we report the results of two independent large scale unbiased approaches to
      identify global protein properties correlating with an extreme thermophile
      lifestyle. First, we performed a comparative proteome analyses using 30 complete
      genome sequences from the three kingdoms. A large difference between the
      proportions of charged versus polar (noncharged) amino acids was found to be a
      signature of all hyperthermophilic organisms. Second, we analyzed the water
      accessible surfaces of 189 protein structures belonging to mesophiles or
      hyperthermophiles. We found that the surfaces of hyperthermophilic proteins
      exhibited the shift already observed at the genomic level, i.e. a proportion of
      solvent accessible charged residues strongly increased at the expense of polar
      residues. The biophysical requirements for the presence of charged residues at
      the protein surface, allowing protein stabilization through ion bonds, is
      therefore clearly imprinted and detectable in all genome sequences available to
      date.

PMID- 10940286
TI  - Quality of life measurement in gastrointestinal and liver disorders.
AB  - Modern medicine has had a considerable impact on mortality rates for serious
      illness. Many chronic diseases which have previously been associated with an
      increased mortality now have survival rates approaching those of the background
      population. However, chronic diseases such as cancer, chronic pain syndromes, and
      chronic inflammatory conditions impose a considerable burden on families, the
      health care system, and society. Health related quality of life (HRQOL) is a
      concept that has developed from the need to estimate the impact of such chronic
      diseases. HRQOL measurement is a conceptual framework which attempts to predict
      daily function and well being based on subjective attitudes and experiences of
      physical, social, and emotional health. It has been evaluated predominantly from
      the patient's viewpoint as proxy respondents appear to underestimate the full
      effect of chronic illness on functional status. Measuring HRQOL in clinical
      research is most frequently undertaken using multi-item questionnaires to
      estimate daily function. Factors which affect HRQOL can be broadly classed as
      disease related and disease independent. The use of different assessment
      techniques permits comparisons between and within disorders. Generic and disease
      specific instruments used together enhance the ability to direct treatment for
      individuals and patient populations. Psychometrically sound questionnaires must
      be used. However, the type of instrument and research methods adopted depend on
      the question of interest. We have attempted to catalogue and critically assess
      the disease specific instruments used in the assessment of chronic
      gastrointestinal disease.

PMID- 10940294
TI  - The PDZ protein TIP-1 interacts with the Rho effector rhotekin and is involved in
      Rho signaling to the serum response element.
AB  - The human T-cell lymphotrophic virus, type 1 Tax protein can interact via its C
      terminus with various proteins including a PDZ domain. In this work, one of them,
      TIP-1, is characterized as a cytoplasmic 14-kDa protein mainly corresponding to
      one PDZ domain. A two-hybrid screen performed with TIP-1 as bait showed that it
      interacts with the human homologue of rhotekin that was previously identified in
      mice as a Rho effector. Both human and mouse rhotekins exhibit at their C termini
      the sequence QSPV-COOH that matches the X(S/T)XV-COOH consensus known for
      proteins recognizing PDZ domains. Mutation of the serine and valine residues to
      alanine impairs interaction of rhotekin with TIP-1. Transient expression
      experiments with a reporter construct including the c-Fos serum response element
      (SRE) showed that coexpression of TIP-1 with the constitutively active RhoA.V14
      mutant and human rhotekin caused a strong activation of the SRE. A negative
      mutant of Rho, RhoA.N19, was unable to cooperate with TIP-1 and rhotekin. The
      positive effect of TIP-1 was also lost when the C terminus of rhotekin was
      mutated. These data show that the complex of active Rho with its effector
      rhotekin bound to TIP-1 produces in the cytoplasm a signal that triggers strong
      activation of the SRE.

PMID- 10940295
TI  - Apolipoprotein E receptors mediate the effects of beta-amyloid on astrocyte
      cultures.
AB  - We have previously shown that beta-amyloid (Abeta) induces astrocyte activation
      in vitro and that this reaction is attenuated by the addition of exogenous
      apolipoprotein E (apoE)-containing particles. However, the effects of Abeta on
      endogenous apoE and apoJ levels and the potential role of apoE receptors in
      astrocyte activation have not been addressed. Three activating stimuli
      (lipopolysaccharide, dibutyryl cAMP, and aged Abeta 1-42) were used to induce
      activation of rat astrocyte cultures, as assessed by changes in morphology and an
      increase in interleukin-1beta. However, only Abeta also induced approximately 50%
      reduction in the amount of released apoE and apoJ and an 8-fold increase in the
      levels of cell-associated apoE and apoJ. Experiments using two concentrations of
      receptor-associated protein, an inhibitor of apoE receptors with a differential
      affinity for the low density lipoprotein receptor (LDLR) and the LDLR-related
      protein (LRP), suggest that LRP mediates Abeta-induced astrocyte activation,
      whereas LDLR mediates the Abeta-induced changes in apoE levels. Receptor
      associated protein had no effect on apoJ levels or on activation by either
      dibutyryl cAMP or lipopolysaccharide. These data suggest that apoE receptors
      translate the presence of extracellular Abeta into cellular responses, both
      initiating and modulating the inflammatory response induced by Abeta.

PMID- 10940297
TI  - Domain III of elongation factor G from Thermus thermophilus is essential for
      induction of GTP hydrolysis on the ribosome.
AB  - Two elongation factors (EF) EF-Tu and EF-G participate in the elongation phase
      during protein biosynthesis on the ribosome. Their functional cycles depend on
      GTP binding and its hydrolysis. The EF-Tu complexed with GTP and aminoacyl-tRNA
      delivers tRNA to the ribosome, whereas EF-G stimulates translocation, a process
      in which tRNA and mRNA movements occur in the ribosome. In the present paper we
      report that: (a) intrinsic GTPase activity of EF-G is influenced by excision of
      its domain III; (b) the EF-G lacking domain III has a 10(3)-fold decreased GTPase
      activity on the ribosome, whereas its affinity for GTP is slightly decreased; and
      (c) the truncated EF-G does not stimulate translocation despite the physical
      presence of domain IV, which is also very important for translocation. By
      contrast, the interactions of the truncated factor with GDP and fusidic acid
      dependent binding of EF-G.GDP complex to the ribosome are not influenced. These
      findings indicate an essential contribution of domain III to activation of GTP
      hydrolysis. These results also suggest conformational changes of the EF-G
      molecule in the course of its interaction with the ribosome that might be induced
      by GTP binding and hydrolysis.

PMID- 10940296
TI  - Chlorination of pyridinium compounds. Possible role of hypochlorite, N
      chloramines, and chlorine in the oxidation of pyridinoline cross-links of
      articular cartilage collagen type II during acute inflammation.
AB  - Reactive oxygen species produced by activated neutrophils and monocytes are
      thought to be involved in mediating the loss of collagen and other matrix
      proteins at sites of inflammation. To evaluate their potential to oxidize the
      pyridinoline (Pyd) cross-links found in collagen types I and II, we reacted
      hydrogen peroxide (H(2)O(2)), hypochlorous acid/hypochlorite (HOCl/OCl(-)), and
      singlet oxygen (O(2)((1)delta g)) with the Pyd substitutes, pyridoxamine
      dihydrochloride and vitamin B(6), which share the same chemical structure and
      spectral properties of Pyd cross-links. Neither H(2)O(2) (125-500 microm) nor
      O(2)((1)delta g) (10-25 microm) significantly changed the spectral properties of
      pyridoxamine or vitamin B(6). Reaction of HOCl/OCl(-) (12.5-50 microm) with
      pyridoxamine at pH 7.2 resulted in a concentration-dependent appearance of two
      new absorbance peaks and a decrease in fluorescence at 400 nm (excitation 325
      nm). The new absorbance peaks correlated with the formation of an N-chloramine
      and the product of its subsequent reaction with pyridoxamine. In contrast, the
      extent to which HOCl reacted with vitamin B(6), which lacks a primary amine
      group, was variable at this pH. At lysosomal pH 5.5, Cl(2)/HOCl/OCl(-) reacted
      with both pyridoxamine and vitamin B(6). Four of the chlorinated products of this
      reaction were identified by gas chromatography-mass spectrometry and included 3
      chloropyridinium, an aldehyde, and several chlorinated products with disrupted
      rings. To evaluate the effects of Cl(2)/HOCl/OCl(-) on Pyd cross-links in
      collagen, we exposed bone collagen type I and articular cartilage type II to
      HOCl. Treatment of either collagen type with HOCl at pH 5. 0 or 7.2 resulted in
      the oxidation of amine groups and, for collagen type II, the specific decrease in
      Pyd cross-link fluorescence, suggesting that during inflammation both oxidations
      may be used by neutrophils and monocytes to promote the loss of matrix integrity.

PMID- 10940298
TI  - c-Cbl is a suppressor of the neu oncogene.
AB  - A rodent oncogenic mutant of the Neu receptor tyrosine kinase is a useful
      experimental model because overexpression of the respective receptor, namely
      HER2/ErbB-2, in human malignancies is associated with relatively aggressive
      diseases. Here we show that the oncogenic form of Neu is constitutively
      associated with the product of the c-cbl proto-oncogene and is part of a large
      complex that includes the phosphoinositide 3-kinase and Shc. Ectopic expression
      of c-Cbl, a ubiquitin-protein isopeptide ligase specific to activated tyrosine
      kinases, causes rapid removal of Neu from the cell surface and severely reduces
      signaling downstream of oncogenic Neu. c-Cbl-induced down-regulation of Neu
      involves covalent attachment of ubiquitin molecules and requires the carboxyl
      terminal domain of Neu. The negative effect of c-Cbl is antagonized by v-Cbl, a
      virus-encoded oncogenic truncated form of c-Cbl. In an in vivo model, infection
      of a Neu-transformed neuroblastoma with a c-Cbl-encoding retrovirus caused
      enhanced down-regulation of Neu and correlated with tumor retardation. Our
      results implicate c-Cbl in negative regulation of Neu and offer a potential
      target for treatment of HER2/ErbB-2-positive human malignancies.

PMID- 10940299
TI  - Annexin VI stimulates endocytosis and is involved in the trafficking of low
      density lipoprotein to the prelysosomal compartment.
AB  - Annexins are calcium-binding proteins with a wide distribution in most polarized
      and nonpolarized cells that participate in a variety of membrane-membrane
      interactions. At the cell surface, annexin VI is thought to remodel the spectrin
      cytoskeleton to facilitate budding of coated pits. However, annexin VI is also
      found in late endocytic compartments in a number of cell types, indicating an
      additional important role at later stages of the endocytic pathway. Therefore
      overexpression of annexin VI in Chinese hamster ovary cells was used to
      investigate its possible role in endocytosis and intracellular trafficking of low
      density lipoprotein (LDL) and transferrin. While overexpression of annexin VI
      alone did not alter endocytosis and degradation of LDL, coexpression of annexin
      VI and LDL receptor resulted in an increase in LDL uptake with a concomitant
      increase of its degradation. Whereas annexin VI showed a wide intracellular
      distribution in resting Chinese hamster ovary cells, it was mainly found in the
      endocytic compartment and remained associated with LDL-containing vesicles even
      at later stages of the endocytic pathway. Thus, data presented in this study
      suggest that after stimulating endocytosis at the cell surface, annexin VI
      remains bound to endocytic vesicles to regulate entry of ligands into the
      prelysosomal compartment.

PMID- 10940300
TI  - Activation of guide RNA-directed editing of a cytochrome b mRNA.
AB  - The coding sequence of several mitochondrial mRNAs of the kinetoplastid protozoa
      is created only after the addition or deletion of specific uridines. Although in
      vitro systems have been valuable in characterizing the editing mechanism, only a
      limited number of mRNAs are accurately edited in vitro. We demonstrate here that
      in vitro editing of cytochrome b mRNA is inhibited by an A-U sequence present on
      both the 5'-untranslated sequence and on a cytochrome b guide RNA. Mutation of
      the sequence on the guide RNA stimulates directed editing and results in the loss
      of binding to at least one component within the editing extract. Mutation of the
      sequence on the mRNA increases the accuracy of the editing. Evidence is provided
      that suggests the A-U sequence interacts with the editing machinery both in vitro
      and in vivo.

PMID- 10940302
TI  - Insulin activation of mitogen-activated protein kinases Erk1,2 is amplified via
      beta-adrenergic receptor expression and requires the integrity of the Tyr350 of
      the receptor.
AB  - Insulin activates a complex set of intracellular responses, including the
      activation of mitogen-activated protein kinases Erk1,2. The counterregulatory
      actions of insulin on catecholamine action are well known and include
      phosphorylation of the beta(2)-adrenergic receptor on Tyr(350), Tyr(354), and
      Tyr(364) in the C-terminal cytoplasmic domain, as well as enhanced sequestration
      of the beta(2)-adrenergic receptor. Both beta-adrenergic agonists and insulin
      provoke sequestration of beta(2)-adrenergic receptors in a synergistic manner. In
      the current work, cross-talk between insulin action and beta(2)-adrenergic
      receptors revealed that insulin activation of Erk1,2 was amplified via beta(2)
      adrenergic receptors. In Chinese hamster ovary cells, expression of beta(2)
      adrenergic receptors enhanced 5-10-fold the activation of Erk1,2 by insulin and
      prolonged the activation, the greatest enhancement occurring at 5 min post
      insulin. The potentiation of insulin signaling on Erk1,2 was proportional to the
      level of expression of beta(2)-adrenergic receptor. The potentiation of insulin
      signaling requires the integrity of Tyr(350) of the beta(2)-adrenergic receptor,
      a residue phosphorylated in response to insulin. beta(2)-adrenergic receptors
      with a Y350F mutation failed to potentiate insulin activation of Erk1,2.
      Expression of the C-terminal domain of the beta(2)-adrenergic receptor (Pro(323)
      Leu(418)) in cells expressing the intact beta(2)-adrenergic receptor acts as a
      dominant negative, blocking the potentiation of insulin activation of Erk1,2 via
      the beta(2)-adrenergic receptor. Blockade of beta(2)-adrenergic receptor
      sequestration does not alter the ability of the beta(2)-adrenergic receptor to
      potentiate insulin action on Erk1,2. We propose a new paradigm in which a G
      protein-linked receptor, such as the beta(2)-adrenergic receptor, itself acts as
      a receptor-based scaffold via its binding site for Src homology 2 domains,
      facilitating signaling of the mitogen-activated protein kinase pathway by
      insulin.

PMID- 10940301
TI  - Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases.
AB  - Gln3p is a GATA-type transcription factor responsive to different nitrogen
      nutrients and starvation in yeast Saccharomyces cerevisiae. Recent evidence has
      linked TOR signaling to Gln3p. Rapamycin causes dephosphorylation and nuclear
      translocation of Gln3p, thereby activating nitrogen catabolite repressible
      sensitive genes. However, a detailed mechanistic understanding of this process is
      lacking. In this study, we show that Tor1p physically interacts with Gln3p. An
      intact TOR kinase domain is essential for the phosphorylation of Gln3p,
      inhibition of Gln3p nuclear entry and repression of Gln3p-dependent
      transcription. In contrast, at least two distinct protein phosphatases, Pph3p and
      the Tap42p-dependent phosphatases, are involved in the activation of Gln3p. The
      yeast pro-prion protein Ure2p binds to both hyper- and hypo-phosphorylated Gln3p.
      In contrast to the free Gln3p, the Ure2p-bound Gln3p is signifcantly resistant to
      dephosphorylation. Taken together, these results reveal a tripartite regulatory
      mechanism by which the phosphorylation of Gln3p is regulated.

PMID- 10940303
TI  - Binding of the general anesthetics propofol and halothane to human serum albumin.
      High resolution crystal structures.
AB  - Human serum albumin (HSA) is one of the most abundant proteins in the circulatory
      system and plays a key role in the transport of fatty acids, metabolites, and
      drugs. For many drugs, binding to serum albumin is a critical determinant of
      their distribution and pharmacokinetics; however, there have as yet been no high
      resolution crystal structures published of drug-albumin complexes. Here we
      describe high resolution crystal structures of HSA with two of the most widely
      used general anesthetics, propofol and halothane. In addition, we describe a
      crystal structure of HSA complexed with both halothane and the fatty acid,
      myristate. We show that the intravenous anesthetic propofol binds at two discrete
      sites on HSA in preformed pockets that have been shown to accommodate fatty
      acids. Similarly we show that the inhalational agent halothane binds (at
      concentrations in the pharmacologically relevant range) at three sites that are
      also fatty acid binding loci. At much higher halothane concentrations, we have
      identified additional sites that are occupied. All of the higher affinity
      anesthetic binding sites are amphiphilic in nature, with both polar and apolar
      parts, and anesthetic binding causes only minor changes in local structure.

PMID- 10940304
TI  - Identification of amino acid residues contributing to the ATP-binding site of a
      purinergic P2X receptor.
AB  - P2X receptor subunits have intracellular N and C termini, two membrane-spanning
      domains, and an extracellular loop of about 280 amino acids. We expressed the rat
      P2X(2) receptor in human embryonic kidney cells, and used alanine-scanning
      mutagenesis on 30 residues with polar side chains conserved among the seven rat
      P2X receptor subunits. This identified a region proximal to the first
      transmembrane domain which contained 2 lysine residues that were critical for the
      action of ATP (Lys(69) and Lys(71)). We substituted cysteines in this region
      (Asp(57) to Asp(71)) and found that for S65C and I67C ATP-evoked currents were
      inhibited by methanethiosulfonates. At I67C, the inhibition by negatively charged
      ethylsulfonate and pentylsulfonate derivatives could be overcome by increasing
      the ATP concentration, consistent with a reduced affinity of ATP binding. The
      inhibitory action of the methanethiosulfonates was prevented by pre-exposure to
      ATP, suggesting occlusion of the binding site. Finally, introduction of negative
      charges into the receptor by mutagenesis at this position (I67E and I67D) also
      gave receptors in which the ATP concentration-response curve was right-shifted.
      The results suggest that residues close to Ile(67) contribute to the ATP-binding
      site.

PMID- 10940305
TI  - The glucagon-like peptide-2 receptor mediates direct inhibition of cellular
      apoptosis via a cAMP-dependent protein kinase-independent pathway.
AB  - Glucagon and the glucagon-like peptides regulate metabolic functions via
      signaling through a glucagon receptor subfamily of G protein-coupled receptors.
      Activation of glucagon-like peptide-2 receptor (GLP-2R) signaling maintains the
      integrity of the intestinal epithelial mucosa via regulation of crypt cell
      proliferation. Because GLP-2 decreases mortality and reduces intestinal apoptosis
      in rodents after experimental injury, we examined whether GLP-2R signaling
      directly modifies the cellular response to external injury. We show here that
      activation of GLP-2R signaling inhibits cycloheximide-induced apoptosis in baby
      hamster kidney fibroblasts expressing a transfected GLP-2 receptor. GLP-2 reduced
      DNA fragmentation and improved cell survival, in association with reduced
      activation of caspase-3 and decreased poly(ADP-ribose) polymerase cleavage and
      reduced caspase-8 and caspase-9-like activities. Both GLP-2 and forskolin reduced
      mitochondrial cytochrome c release and decreased the cycloheximide-induced
      cleavage of caspase-3 in the presence or absence of the PKA inhibitor H-89.
      Similarly, GLP-2 increased cell survival following cycloheximide in the presence
      of the kinase inhibitors PD98054 and LY294002. These findings provide evidence
      that signaling through G protein-coupled receptors of the glucagon superfamily is
      directly linked to regulation of apoptosis and suggest the existence of a cAMP
      dependent protein kinase-, phosphatidylinositol 3-kinase-, and mitogen-activated
      protein kinase-independent pathway coupling GLP-2R signaling to caspase
      inhibition and cell survival.

PMID- 10940306
TI  - Characterization of the repressor function of the nuclear orphan receptor
      retinoid receptor-related testis-associated receptor/germ cell nuclear factor.
AB  - Retinoid receptor-related testis-associated receptor (RTR)/germ cell nuclear
      factor is a nuclear orphan receptor that plays an important role in the control
      of gene expression during early embryonic development and gametogenesis. It has
      been shown to repress transcriptional activation. In this study, we further
      characterize this repressor function. We demonstrate that RTR can suppress the
      transcriptional activation induced by the estrogen receptor related-receptor
      alpha1 through its response element. The latter is at least in part due to
      competition for binding to the same response element. In addition, RTR inhibits
      basal transcriptional activation, indicating that it functions as an active
      repressor. Mammalian two-hybrid analyses showed that RTR interacts with the co
      repressor nuclear co-repressor (N-CoR) but is unable to interact with the co
      repressor SMRT or RIP140. Pull-down analyses with glutathione S-transferase-RTR
      fusion protein demonstrated that RTR physically interacts with N-CoR in vitro,
      suggesting a potential role for N-CoR in the transcriptional repression by RTR.
      To identify the regions in RTR essential for the binding of RTR to N-CoR, the
      effect of various deletion and point mutations on this interaction was examined.
      This analysis revealed that this interaction requires the hinge domain, helix 3
      as well as the helix 12 region of RTR. The residues Ser(246)-Tyr(247) in the
      hinge domain, Lys(318) in helix 3, and Lys(489)-Thr(490) in helix 12 are
      identified as being critical in this interaction. Our results demonstrate that
      RTR can function as an active transcriptional repressor and that this repression
      can be mediated through interactions with the co-repressor N-CoR. We show that
      this interaction exhibits several characteristics unique to RTR. Through its
      repressor function, RTR can suppress the induction of transcriptional activation
      by other nuclear receptors. These repressor activities may provide important
      mechanisms by which RTR regulates gene expression during development and
      gametogenesis.

PMID- 10940307
TI  - Unique role of the chemokine domain of fractalkine in cell capture. Kinetics of
      receptor dissociation correlate with cell adhesion.
AB  - The chemokine fractalkine (FK) has two structural features that make it unique in
      the chemokine family: a CX(3)C motif and an extended carboxyl terminus that
      anchors it to the cell surface. This mucin-like stalk or an equivalent spacer is
      required for FK to mediate the adhesion of cells expressing its receptor,
      CX(3)CR1. To determine whether the ability of FK to act as a cell adhesion
      molecule is due to the unique presentation of a chemokine domain on a stalk or to
      properties of the chemokine domain itself, we created a series of chimeras in
      which other soluble chemokines (RANTES (regulated on activation normal T cell
      expressed), monocyte chemoattractant protein 1, macrophage inflammatory protein 1
      beta, secondary lymphoid tissue chemokine, and interleukin 8) were fused to the
      mucin stalk. When tested in a static-cell adhesion assay, many of these chemokine
      chimeras demonstrated activity equivalent to that of FK. In flow assays, however,
      none of the chimeras captured cells as efficiently as FK. Interestingly, FK
      captured cells expressing either CX(3)CR1 or the viral receptor US28. Cells bound
      to FK without rolling or detaching, whereas the interleukin 8 and monocyte
      chemoattractant protein 1 chimeras induced primarily cell rolling and detaching,
      respectively. In binding studies, FK has a significantly slower off-rate from its
      receptors than any of the other chemokine chimeras had for their cognate
      receptors. We conclude that presentation of a chemokine atop a mucin-like stalk
      is not, in and of itself, sufficient to capture cells. The unique ability of FK
      to mediate adhesion under flow may be a function of its slow receptor off-rate.

PMID- 10940310
TI  - RNA polymerase I holoenzyme-promoter interactions.
AB  - In plants and animals, RNA polymerase I (pol I) can be purified in a form that is
      self-sufficient for accurate rRNA gene promoter-dependent transcription and that
      has biochemical properties suggestive of a single complex, or holoenzyme. In this
      study, we examined the promoter binding properties of a highly purified Brassica
      pol I holoenzyme activity. DNase I footprinting revealed protection of the core
      promoter region from approximately -30 to +20, in good agreement with the
      boundaries of the minimal promoter defined by deletion analyses (-33 to +6).
      Using conventional polyacrylamide electrophoretic mobility shift assays (EMSA),
      protein-DNA complexes were mostly excluded from the gel. However, agarose EMSA
      revealed promoter-specific binding activity that co-purified with promoter
      dependent transcription activity. Titration, time-course, and competition
      experiments revealed the formation or dissociation of a single protein-DNA
      complex. This protein-DNA complex could be labeled by incorporation of
      radioactive ribonucleotides into RNA in the presence of alpha-amanitin,
      suggesting that the polymerase I enzyme is part of the complex. Collectively,
      these results suggest that transcriptionally competent pol I holoenzymes can
      associate with rRNA gene promoters in a single DNA binding event.

PMID- 10940308
TI  - Structural basis for the species-specific activity of TFIIS.
AB  - Many proteins involved in eukaryotic transcription are similar in function and in
      sequence between organisms. Despite the sequence similarities, there are many
      factors that do not function across species. For example, transcript elongation
      factor TFIIS is highly conserved among eukaryotes, and yet the TFIIS protein from
      Saccharomyces cerevisiae cannot function with mammalian RNA polymerase II and
      vice versa. To determine the reason for this species specificity, chimeras were
      constructed linking three structurally independent regions of the TFIIS proteins
      from yeast and human cells. Two independently folding domains, II and III, have
      been examined previously using NMR (). Yeast domain II alone is able to bind
      yeast RNA polymerase II with the same affinity as the full-length TFIIS protein,
      and this domain was expected to confer the species selectivity. Domain III has
      previously been shown to be readily exchanged between mammalian and yeast
      factors. However, the results presented here indicate that domain II is
      insufficient to confer species selectivity, and a primary determinant lies in a
      30-amino acid highly conserved linker region connecting domain II with domain
      III. These 30 amino acids may physically orient domains II and III to support
      functional interactions between TFIIS and RNA polymerase II.

PMID- 10940309
TI  - Interaction of protein kinase C and cAMP-dependent pathways in the
      phosphorylation of the Na,K-ATPase.
AB  - To test the hypothesis that there is cross-talk between the protein kinase C
      (PKC) and protein kinase A (PKA) pathways in the regulation of the Na,K-ATPase,
      we measured its phosphorylation in mammalian cell cultures. Phosphorylation of
      the PKC site, Ser-18, appeared to be due to the activation of the alpha isoform
      of the kinase. In NRK-52E and L6 cells, this phosphorylation was reduced by prior
      activation of a cAMP-dependent signaling pathway with forskolin. In principle
      this would be consistent with direct interaction between the two phosphorylation
      sites, but further investigation suggested a more indirect mechanism. First,
      phosphorylation of Ser-938, the PKA site, could not be detected despite the
      presence of active PKA. Second, there was a major reduction in the
      phosphorylation of unrelated phosphoproteins as a consequence of elevation of
      cAMP, suggesting generalized reduction of kinase activity or activation of
      phosphatase activity. In NRK-52E and L6, phosphorylation of the Na, K-ATPase at
      Ser-18 paralleled this global change. In C6 cells, in contrast, there was no cAMP
      effect on Na,K-ATPase phosphorylation at Ser-18 and no global cAMP effect on
      other phosphoproteins. The cross-talk is evidently mediated by events occurring
      at the cellular level.

PMID- 10940311
TI  - Structural requirements for the stability and microsomal transport activity of
      the human glucose 6-phosphate transporter.
AB  - Deficiencies in glucose 6-phosphate (G6P) transporter (G6PT), a 10-helical
      endoplasmic reticulum transmembrane protein of 429 amino acids, cause glycogen
      storage disease type 1b. To date, only three missense mutations in G6PT have been
      shown to abolish microsomal G6P transport activity. Here, we report the results
      of structure-function studies on human G6PT and demonstrate that 15 missense
      mutations and a codon deletion (delta F93) mutation abolish microsomal G6P uptake
      activity and that two splicing mutations cause exon skipping. While most missense
      mutants support the synthesis of G6PT protein similar to that of the wild-type
      transporter, immunoblot analysis shows that G20D, delta F93, and I278N mutations,
      located in helix 1, 2, and 6, respectively, destabilize the G6PT. Further, we
      demonstrate that G6PT mutants lacking an intact helix 10 are misfolded and
      undergo degradation within cells. Moreover, amino acids 415-417 in the
      cytoplasmic tail of the carboxyl-domain, extending from helix 10, also play a
      critical role in the correct folding of the transporter. However, the last 12
      amino acids of the cytoplasmic tail play no essential role(s) in functional
      integrity of the G6PT. Our results, for the first time, elucidate the structural
      requirements for the stability and transport activity of the G6PT protein.

PMID- 10940312
TI  - Protein kinase C alpha controls erythropoietin receptor signaling.
AB  - Protein kinase C (PKC) is implied in the activation of multiple targets of
      erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal
      transduction and in the regulation of erythroid proliferation and differentiation
      remained elusive. We analyzed the effect of PKC inhibitors with distinct modes of
      action on EpoR signaling in primary human erythroblasts and in a recently
      established murine erythroid cell line. Active PKC appeared essential for Epo
      induced phosphorylation of the Epo receptor itself, STAT5, Gab1, Erk1/2, AKT, and
      other downstream targets. Under the same conditions, stem cell factor-induced
      signal transduction was not impaired. LY294002, a specific inhibitor of
      phosphoinositol 3-kinase, also suppressed Epo-induced signal transduction, which
      could be partially relieved by activators of PKC. PKC inhibitors or LY294002 did
      not affect membrane expression of the EpoR, the association of JAK2 with the
      EpoR, or the in vitro kinase activity of JAK2. The data suggest that PKC controls
      EpoR signaling instead of being a downstream effector. PKC and phosphoinositol 3
      kinase may act in concert to regulate association of the EpoR complex such that
      it is responsive to ligand stimulation. Reduced PKC-activity inhibited Epo
      dependent differentiation, although it did not effect Epo-dependent "renewal
      divisions" induced in the presence of Epo, stem cell factor, and dexamethasone.

PMID- 10940313
TI  - Recognition and ubiquitination of Notch by Itch, a hect-type E3 ubiquitin ligase.
AB  - Genetic studies identified Itch, which is a homologous to the E6-associated
      protein carboxyl terminus (Hect) domain-containing E3 ubiquitin-protein ligase
      that is disrupted in non-agouti lethal mice or Itchy mice. Itch-deficiency
      results in abnormal immune responses and constant itching in the skin. Here, Itch
      was shown to associate with Notch, a protein involved in cell fate decision in
      many mammalian cell types, including cells in the immune system. Itch binds to
      the N-terminal portion of the Notch intracellular domain via its WW domains and
      promotes ubiquitination of Notch through its Hect ubiquitin ligase domain. Thus,
      Itch may participate in the regulation of immune responses by modifying Notch
      mediated signaling.

PMID- 10940317
TI  - A conserved nuclease domain in the archaeal Holliday junction resolving enzyme
      Hjc.
AB  - Holliday junction resolving enzymes are ubiquitous proteins that function in the
      pathway of homologous recombination, catalyzing the rearrangement and repair of
      DNA. They are metal ion-dependent endonucleases with strong structural
      specificity for branched DNA species. Whereas the eukaryotic nuclear enzyme
      remains unknown, an archaeal Holliday junction resolving enzyme, Hjc, has
      recently been identified. We demonstrate that Hjc manipulates the global
      structure of the Holliday junction into a 2-fold symmetric X shape, with local
      disruption of base pairing around the point of cleavage that occurs in a region
      of duplex DNA 3' to the point of strand exchange. Primary and secondary
      structural analysis reveals the presence of a conserved catalytic metal ion
      binding domain in Hjc that has been identified previously in several restriction
      enzymes. The roles of catalytic residues conserved within this domain have been
      confirmed by site-directed mutagenesis. This is the first example of this domain
      in an archaeal enzyme of known function as well as the first in a Holliday
      junction resolving enzyme.

PMID- 10940315
TI  - Regulation of connexin degradation as a mechanism to increase gap junction
      assembly and function.
AB  - Connexins, the integral membrane protein constituents of gap junctions, are
      degraded at a rate (t(12) = 1.5-5 h) much faster than most other cell surface
      proteins. Although the turnover of connexins has been shown to be sensitive to
      inhibitors of either the lysosome or of the proteasome, how connexins are
      targeted for degradation and whether this process can be regulated to affect
      intercellular communication is unknown. We show here that reducing connexin
      degradation with inhibitors of the proteasome (but not with lysosomal blockers)
      is associated with a striking increase in gap junction assembly and intercellular
      dye transfer in cells inefficient in both processes under basal conditions. The
      effect of proteasome inhibitors on wild-type connexin stability, assembly, and
      function was mimicked by treatment of assembly-inefficient cells with inhibitors
      of protein synthesis such as cycloheximide. Sensitivity of connexin degradation
      to cycloheximide, but not to proteasome inhibitors, was abolished when connexins
      were rendered structurally abnormal by perturbation of essential disulfide bonds
      or by mutation. Our findings provide the first evidence that intercellular
      communication can be up-regulated at the level of connexin turnover and that a
      short-lived protein may be required for conformationally mature connexins to
      become substrates of proteasomal degradation.

PMID- 10940316
TI  - Topoisomerase II is required for mitoxantrone to signal nuclear factor kappa B
      activation in HL60 cells.
AB  - Topoisomerase II is a target for a number of chemotherapeutic agents used in the
      treatment of cancer. Its essential physiological role in modifying the topology
      of DNA involves the generation of transient double-strand breaks. Anti-cancer
      drugs, such as mitoxantrone, that target this enzyme interrupt its catalytic
      cycle and give rise to persistent double strand breaks, which may be lethal to a
      cell. We investigated the role of such lesions in signaling the activation of the
      transcription factor nuclear factor kappaB (NFkappaB) by this drug. Mitoxantrone
      activated NFkappaB and stimulated IkappaBalpha degradation in the promyelocytic
      leukemia cell line HL60 but not in the variant cells, HL60/MX2 cells, which lack
      the beta isoform of topoisomerase II and express a truncated alpha isoform that
      results in an altered subcellular distribution. Treatment of sensitive HL60 cells
      with mitoxantrone led to a depletion of both isoforms, suggesting the
      stabilization of transient DNA-topoisomerase II complexes. This depletion was
      absent in the variant cells, HL60/MX2. Activation of caspase 3 by mitoxantrone
      was also impaired in the HL60/MX2 cells. NFkappaB activation in response to tumor
      necrosis factor and bleomycin, the latter causing topoisomerase II-independent
      DNA damage, was intact in both cell lines. An inhibitor rather than a poison of
      topoisomerase II, Imperial Cancer Research Fund 187 (ICRF 187) the mechanism of
      which does not involve the generation of double strand breaks, did not activate
      NFkappaB, nor did it induce apoptosis in parental HL60 cells. However, ICRF 187
      protected against IkappaB degradation in parental HL60 cells in response to
      mitoxantrone. This protection was also shown with another topoisomerase II
      inhibitor, merbarone, which is structurally and functionally distinct from ICRF
      187. Their effects were specific, as neither protected against tumor necrosis
      factor-stimulated IkappaB degradation. The poisoning of topoiso- merase II with
      resultant DNA damage is therefore a critical signal for NFkappaB activation.

PMID- 10940319
TI  - Learning motor synergies makes use of information on muscular load.
AB  - Prism adaptation, a form of procedural learning, requires the integration of
      visual and motor information for its proper acquisition. Although the role of the
      visual feedback has begun to be understood, the nature of the motor information
      necessary for the development of the adaptation remains unknown. In this work we
      have tested the idea that modifying the arm load at different stages of the
      adaptation process, and the ensuing change of motor information perceived by the
      subjects, would modify the final properties of the adaptation. We trained a set
      of subjects to throw balls to a target while wearing prism glasses and varied the
      weight of their arms at different time points during the task. We observed that
      the acquisition of the adaptation was not affected by the change in load.
      However, its persistence (i.e., the aftereffect) was reduced when tested under a
      weight condition different from the training trials. Furthermore, when the
      training weight conditions were restored later during testing, a second, late
      aftereffect was unmasked, suggesting that the missing aftereffect did not
      disappear but had remained latent. Our results show that the internal
      representation of a motor memory incorporates information about load conditions
      and that the memory stored under a specific weight condition can be fully
      retrieved only when the original training condition is restored.

PMID- 10940320
TI  - A behavioral and genetic dissection of two forms of olfactory plasticity in
      Caenorhabditis elegans: adaptation and habituation.
AB  - Continuous presentation of an olfactory stimulus causes a decrement of the
      chemotaxis response in the nematode Caenorhabditis elegans. However, the
      differences between the learning process of habituation (a readily reversible
      decrease in behavioral response) and other types of olfactory plasticity such as
      adaptation (a decrement in response due to sensory fatigue, which cannot be
      dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was
      used within a single paradigm to assess the distinct processes of olfactory
      adaptation and habituation. Preexposing and testing worms to 100% DA vapors
      caused a chemotaxis decrement that was not reversible despite the presentation of
      potentially dishabituating stimuli. This DA adaptation was abolished in worms
      with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron),
      even though naive chemotaxis remained unaffected. Conversely, DA adaptation
      remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory
      behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure
      to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause
      worms to exhibit any response decrement. In contrast to preexposure to high DA
      concentrations, preexposure to low DA concentrations (0.001%) produced
      habituation of the chemotaxis response (a dishabituating stimulus could reverse
      the response decrement back to baseline levels). The distinct behavioral effects
      produced by DA preexposure highlight a concentration-dependent dissociation
      between two decremental olfactory processes: adaptation at high DA concentrations
      versus habituation at low DA concentrations.

PMID- 10940321
TI  - Inhibition of passive-avoidance memory formation in the day-old chick by the
      opioid cytochrophin-4.
AB  - Cytochrophin-4 (cyt-4), a tetrapeptide with opioid-like activity, caused amnesia
      when injected into chick forebrain 5 hr after passive-avoidance training.
      Bilateral injections of cyt-4 directly into the lobus parolfactorius (LPO)
      resulted in the chicks being amnesic for the training task 24 hr later, whereas
      unilateral injections of cyt-4 were effective only when injected into the right
      LPO. Cyt-4-induced amnesia was reversed by the general opioid antagonist,
      naloxone, indicating that cyt-4 was acting via an opioid receptor. The mu- and
      delta-opioid receptors (but not kappa-opioid or ORL(1)-receptors) have been shown
      to be involved in memory formation 5 hr after training (). Because an antagonist
      of the mu-opioid receptor inhibited memory, we attempted to reverse the effect of
      cyt-4 using mu-opioid receptor agonists. Met[enk] was unable to reverse the
      inhibition of memory formation by cyt-4 suggesting that the mu-opioid receptor is
      not involved in this effect. However endomorphin-2 (endo-2) reversed the effect
      of cyt-4. We further investigated the action of endo-2 using an irreversible
      antagonist of the mu-receptor, beta-funaltrexamine (beta-FAN), and found that
      endo-2 reversed beta-FAN-induced amnesia indicating that endo-2 was not acting on
      the mu-opioid receptor in the chick. Because unilateral injections of beta-FAN
      were not amnesic (bilateral injections were amnesic) this provided further
      evidence that the effect of cyt-4 was not mediated via the mu-opioid receptor.
      Coinjection of the delta-receptor agonist, (D-Pen(2), L-Pen(5))enkephalin
      (DPLPE), reversed the disruptive effect of cyt-4 on memory. However, memory
      modulation via the delta-opioid receptor was not lateralized to the right
      hemisphere suggesting that cyt-4 does not act via this receptor either. It was
      shown that an antagonist of the epsilon-opioid receptor inhibited memory at the 5
      hr time point. We conclude that the epsilon-opioid receptor or an unidentified
      opioid receptor subtype could be involved in the action of cyt-4.

PMID- 10940324
TI  - From chick nutrition to nutrition policy.
AB  - It is difficult to abstract a summary of a lifetime of work. I have chosen to
      discuss research on protein, calcium, and the effects of dietary fat and
      cholesterol on serum cholesterol and on my activities that led to the publication
      of the Dietary Guidelines for Americans. Among the conclusions from studies on
      protein and calcium is that reasonably healthy people are adapted to their
      current diets. People all over the world, for example, are raised on relatively
      low calcium intakes yet have less osteoporosis than those who consume western
      style diets. They also appear to do reasonably well on low-lysine intakes.
      Attempts to define requirements need to allow for adaptation, and we need to
      determine whether such adaptations are beneficial or detrimental to health. The
      studies on serum cholesterol defined the role of the various classes of fatty
      acids. The publication of the Dietary Guidelines for Americans introduced a new
      era of nutrition and has radically altered nutrition policy, nutrition standards,
      and education.

PMID- 10940323
TI  - Enhancement of glutamate release by L-fucose changes effects of glutamate
      receptor antagonists on long-term potentiation in the rat hippocampus.
AB  - In previous studies L-fucose has been shown to facilitate long-term memory
      formation and to enhance and prolong long-term potentiation (LTP). To search for
      possible presynaptic or postsynaptic mechanisms that are affected by L-fucose, we
      examined the effect of L-fucose on (1) inhibition of LTP induction via glutamate
      receptors by antagonists, (2) paired-pulse facilitation, and (3) presynaptic
      transmitter release. Coapplication of 0.2 mM L-fucose with the competitive N
      methyl-D-aspartate (NMDA) receptor antagonist, D-2-amino-5-phosphonovalerate
      (AP5), or coapplication of 0.2 mM L-fucose in the presence of an inhibitor for
      class I/II metabotropic glutamate receptors, (S)-alpha-methyl-4
      carboxyphenylglycine (MCPG), reversed LTP blockade in the CA1-region of
      hippocampal slices. In contrast, L-fucose had no effect on the LTP blockade by
      the noncompetitive NMDA ion-channel blocker (5R,10S)-(+)-5-Methyl-10, 11-dihydro
      5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK-801). Paired-pulse
      facilitation, which is a primarily presynaptic phenomenon of short-term
      plasticity, was decreased in the presence of 0.2 mM L-fucose. Furthermore, L
      fucose enhanced the K(+)-stimulated release of [(3)H]-D-aspartate from preloaded
      hippocampal slices in a concentration-dependent manner. These observations
      demonstrate an influence of L-fucose on transmitter release that in turn can
      increase transmitter availability at postsynaptic glutamate receptors. This
      effect of L-fucose may contribute to the LTP facilitation seen in vitro and in
      vivo as well as to improvement in memory formation.

PMID- 10940322
TI  - Inhibition of nitric oxide synthesis and gene knockout of neuronal nitric oxide
      synthase impaired adaptation of mouse optokinetic response eye movements.
AB  - Nitric oxide (NO) plays a key role in synaptic transmission efficiency in the
      central nervous system. To gain an insight on the role of NO in cerebellar
      functions, we, here, measured the dynamics of the horizontal optokinetic response
      (HOKR) and vestibulo-ocular reflex (HVOR), and the adaptation of HOKR in mice
      locally injected with N(G)-monomethyl-L-arginine (L-NMMA) that inhibits NO
      synthesis and in mice devoid of neuronal nitric oxide synthase (nNOS). Local
      application of L-NMMA into the cerebellar flocculi induced no change in the
      dynamics of the HOKR but markedly depressed the adaptation of the HOKR induced by
      1 hr of sustained screen oscillation. A slight difference was seen in the HOKR
      but not in the HVOR dynamics between nNOS(-/-) mutant and wild-type mice. One
      hour of sustained screen oscillation induced adaptation of the HOKR gains in wild
      type mice but not in mutants. These observations suggest that NO is essential for
      the adaptation of the HOKR and that nNOS is the major enzyme for NO synthesis in
      the process.

PMID- 10940325
TI  - The behavioral determinants of exercise: implications for physical activity
      interventions.
AB  - In light of the well-documented health benefits of physical activity and the fact
      that the majority of adult men and women are inactive, promoting regular physical
      activity is a public health priority. This chapter reviews current research
      findings regarding the determinants of exercise behavior. It also discusses the
      implications of this knowledge for individual and public health recommendations
      and intervention strategies for promoting physical activity. The discussion is
      predicated on the belief that physical activity is a complex, dynamic process.
      During their lives, individuals typically move through various phases of exercise
      participation that are determined by diverse factors. This chapter discusses
      physical activity determinants in two broad categories: individual
      characteristics, including motivations, self-efficacy, exercise history, skills,
      and other health behaviors; and environmental characteristics such as access,
      cost, and time barriers and social and cultural supports.

PMID- 10940326
TI  - Leptin--much more than a satiety signal.
AB  - Much attention has focused on the effects of leptin as a central satiety agent.
      There is now a significant amount of evidence that leptin is active in the
      periphery. This review focuses on the ability of leptin to modify insulin
      sensitivity, tissue metabolism, stress responses, and reproductive function.
      Leptin's effect on several of these systems is mediated via the hypothalamic
      pituitary axis. Therefore, although in vitro studies provide evidence for direct
      effects on specific tissues and metabolic pathways, it is essential to consider
      the interactions between leptin and other regulatory factors in vivo. Little is
      known about the regulation of peripheral receptor expression or the production of
      binding proteins. Both of these factors determine the bioactivity of circulating
      leptin and have the potential to induce a peripheral resistance to leptin,
      similar to the central "leptin resistance" observed in obese subjects. Future
      research will clarify which of the endocrine and metabolic actions of peripheral
      leptin are of physiological relevance and which should be considered a
      pharmacological manipulation.

PMID- 10940327
TI  - Physiological and nutritional regulation of enzymes of triacylglycerol synthesis.
AB  - Although triacylglycerol stores play the critical role in an organism's ability
      to withstand fuel deprivation and are strongly associated with such disorders as
      diabetes, obesity, and atherosclerotic heart disease, information concerning the
      enzymes of triacylglycerol synthesis, their regulation by hormones, nutrients,
      and physiological conditions, their mechanisms of action, and the roles of
      specific isoforms has been limited by a lack of cloned cDNAs and purified
      proteins. Fortunately, molecular tools for several key enzymes in the synthetic
      pathway are becoming available. This review summarizes recent studies of these
      enzymes, their regulation under varying physiological conditions, their purported
      roles in synthesis of triacylglycerol and related glycerolipids, the possible
      functions of different isoenzymes, and the evidence for specialized cellular
      pools of triacylglycerol and glycerolipid intermediates.

PMID- 10940328
TI  - Regulation of metabolism and body fat mass by leptin.
AB  - The relative stability of body weight over the long term and under a variety of
      environmental conditions that alter short-term energy intake and expenditure
      provides strong evidence for the regulation of body energy content. The
      lipostatic theory of energy balance regulation proposed 40 years ago that
      circulating factors, generated in proportion to body fat stores, acted as signals
      to the brain, eliciting changes in energy intake and expenditure. The discovery
      of leptin and its receptors has now provided a molecular basis for this theory.
      Leptin functions as much more than an adipocyte-derived signal of lipid stores,
      however. Although suppression of food intake is an important centrally mediated
      effect of leptin, considerable evidence indicates that leptin also functions both
      directly and indirectly, via the brain, to orchestrate complex metabolic changes
      in a number of organs and tissues, altering nutrient flux to favor energy
      expenditure over energy storage.

PMID- 10940329
TI  - Iron transport.
AB  - Iron homeostasis is maintained by regulating its absorption: Under conditions of
      deficiency, assimilation is enhanced but iron uptake is otherwise limited to
      prevent toxicity due to overload. Iron deficiency remains the most important
      micronutrient deficiency worldwide, but increasing awareness of the genetic basis
      for iron-loading diseases points to iron overload as a major public health issue
      as well. Recent identification of mutant alleles causing iron uptake disorders in
      mice and humans provides new insights into the mechanisms involved in iron
      transport and its regulation. This article summarizes these discoveries and
      discusses their impact on our current understanding of iron transport and its
      regulation.

PMID- 10940331
TI  - APOLIPOPROTEIN B: mRNA editing, lipoprotein assembly, and presecretory
      degradation.
AB  - Apolipoprotein (apo)B circulates in two distinct forms, apoB100 and apoB48. Human
      liver secretes apoB100, the product of a large mRNA encoding 4536 residues. The
      small intestine of all mammals secretes apoB48, which arises following C-to-U
      deamination of a single cytidine base in the nuclear apoB transcript, introducing
      a translational stop codon. This process, referred to as apoB RNA editing,
      operates through a multicomponent enzyme complex that contains a single catalytic
      subunit, apobec-1, in addition to other protein factors that have yet to be
      cloned. ApoB RNA editing also exhibits stringent cis-acting requirements that
      include both structural and sequence-specific elements-specifically efficiency
      elements that flank the minimal cassette, an AU-rich RNA context, and an 11
      nucleotide mooring sequence-located in proximity to a suitably positioned
      (usually upstream) cytidine. C-to-U RNA editing may become unconstrained under
      circumstances where apobec-1 is overexpressed, in which case multiple cytidines
      in apoB RNA, as well as in other transcripts, undergo C-to-U editing. ApoB RNA
      editing is eliminated following targeting of apobec-1, establishing that there is
      no genetic redundancy in this function. Under physiological circumstances, apoB
      RNA editing exhibits developmental, hormonal, and nutritional regulation, in some
      cases related to transcriptional regulation of apobec-1 mRNA. ApoB and the
      microsomal triglyceride transfer protein (MTP) are essential for the assembly and
      secretion of apoB-containing lipoproteins. MTP functions by transferring lipid to
      apoB during its translation and by transporting triglycerides into the
      endoplasmic reticulum to form apoB-free lipid droplets. These droplets fuse with
      nascent apoB-containing particles to form mature, very low-density lipoproteins
      or chylomicrons. In cultured hepatic cells, lipid availability dictates the rate
      of apoB production. Unlipidated or underlipidated forms of apoB are subjected to
      presecretory degradation, a process mediated by retrograde transport from the
      lumen of the endoplasmic reticulum to the cytosol, coupled with
      multiubquitination and proteasomal degradation. Although control of lipid
      secretion in vivo is primarily achieved at the level of lipoprotein particle
      size, regulation of apoB production by presecretory degradation may be relevant
      in some dyslipidemic states.

PMID- 10940330
TI  - Biosynthesis of vitamin b2 (riboflavin).
AB  - The biosynthesis of one riboflavin molecule requires one molecule of GTP and two
      molecules of ribulose 5-phosphate as substrates. The imidazole ring of GTP is
      hydrolytically opened, yielding a 4, 5-diaminopyrimidine which is converted to 5
      amino-6-ribitylamino-2, 4(1H,3H)-pyrimidinedione by a sequence of deamination,
      side chain reduction and dephosphorylation. Condensation of 5-amino-6
      ribitylamino-2,4(1H,3H)-pyrimidinedione with 3, 4-dihydroxy-2-butanone 4
      phosphate obtained from ribulose 5-phosphate affords 6,7-dimethyl-8
      ribityllumazine. Dismutation of the lumazine derivative yields riboflavin and 5
      amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione, which is recycled in the
      biosynthetic pathway. The structure of the biosynthetic enzyme, 6,7-dimethyl-8
      ribityllumazine synthase, has been studied in considerable detail.

PMID- 10940332
TI  - Intestinal transport during fasting and malnutrition.
AB  - Fasting or malnutrition (FM) has dramatic effects on small intestinal mucosal
      structure and transport function. Intestinal secretion of ions and fluid is
      increased by FM both under basal conditions and in response to secretory
      agonists. Intestinal permeability to ions and macromolecules may also be elevated
      by FM, which increases the potential for fluid and electrolyte losses and for
      anaphylactic responses to luminal antigens. Mucosal atrophy induced by FM reduces
      total intestinal absorption of nutrients, but nutrient absorption normalized to
      mucosal mass may actually be enhanced by a variety of mechanisms, including
      increased transporter gene expression, electrochemical gradients, and ratio of
      mature to immature cells. These observations underscore the value of enteral
      feeding during health and disease.

PMID- 10940333
TI  - Dietary fat and breast cancer.
AB  - One of the most often studied associations in epidemiology is dietary fat and
      breast cancer risk. That migrants from low-risk countries increase their risk on
      immigrating to higher-risk countries suggests that some modifiable lifestyle or
      environmental factor is responsible for the development of breast cancer.
      Although early international correlational studies and experimental animals
      studies support dietary fat as a risk factor for breast cancer, more recent data
      from case-control studies and cohort studies have been equivocal, thus the
      analytical data do not support a strong positive association. The conflicting
      results from analytic studies may be due to methodologic issues associated with
      study design, dietary assessment tools, measurement error, improper statistical
      analyses, and a lack of heterogeneity in fat intake among the study population.
      Moreover, current dietary questionnaires may be inadequate in capturing true
      dietary intakes or capturing the risk with exposure during earlier periods of a
      woman's life. Although two large clinical trials investigating the fat/breast
      cancer relationships issue are underway, researchers are generally skeptical at
      their ability to detect an independent association between fat and breast cancer
      risk. Further epidemiologic studies using current methodology may not prove to be
      fruitful in generating definitive answers to shed light on this controversial
      issue. In addition, rather than concentrating on dietary fat, researchers should
      focus on diets that are not only low in saturated fat, but also high in fruit and
      vegetable consumption. Researchers should take advantage of advances in molecular
      and genetic technology for a different perspective in examining the issue. For
      example, markers of susceptibility to breast cancer that can detect women at
      higher risk for breast cancer may be helpful in clarifying the role of dietary
      fat. More comprehensive and multiple approaches to studying dietary factors and
      breast cancer are recommended.

PMID- 10940334
TI  - Calcium in pregnancy and lactation.
AB  - Pregnancy and lactation are periods of high calcium requirement. This review
      highlights recent advances in our understanding of calcium and bone metabolism
      during human pregnancy and lactation and discusses the findings in relation to
      the calcium nutrition of the mother. The evidence indicates that pregnancy and
      lactation are characterized by physiological adaptive processes that are
      independent of maternal calcium intake and that provide the calcium necessary for
      fetal growth and breast-milk production without requiring an increase in maternal
      calcium intake. There are firm data that demonstrate that a low calcium intake
      during lactation does not lead to impaired lactational performance or to
      exaggerated bone loss. However, more research is required to define whether a low
      calcium intake prior to or during pregnancy can have deleterious effects on
      reproductive and lactational performance, and on the long-term health of the
      mother and child.

PMID- 10940335
TI  - Retention of iron by infants.
AB  - Throughout the world, the most common nutritional deficiency disorder of infants
      is iron deficiency. Developing effective strategies for preventing iron
      deficiency requires detailed knowledge of iron retention under ordinary living
      conditions. For the adult population, such knowledge is at an advanced stage, but
      relatively little is known about infants. Many reports of iron retention by
      infants have been based on the assumption that, as in normal and iron-deficient
      adults, 80%-100% of newly absorbed iron is promptly incorporated into circulating
      erythrocytes, but this assumption is not supported by available data. This
      communication presents a review of iron retention by term and preterm infants, as
      determined by metabolic balance studies or (59)Fe whole-body counting studies,
      and it explores the relationship between iron retention and postnatal age, iron
      nutritional status, iron intake (or dose), and type of feeding.

PMID- 10940336
TI  - Cellular copper transport and metabolism.
AB  - The transport and cellular metabolism of Cu depends on a series of membrane
      proteins and smaller soluble peptides that comprise a functionally integrated
      system for maintaining cellular Cu homeostasis. Inward transport across the
      plasma membrane appears to be a function of integral membrane proteins that form
      the channels that select Cu ions for passage. Two membrane-bound Cu-transporting
      ATPase enzymes, ATP7A and ATP7B, the products of the Menkes and Wilson disease
      genes, respectively, catalyze an ATP-dependent transfer of Cu to intracellular
      compartments or expel Cu from the cell. ATP7A and ATP7B work in concert with a
      series of smaller peptides, the copper chaperones, that exchange Cu at the ATPase
      sites or incorporate the Cu directly into the structure of Cu-dependent enzymes
      such as cytochrome c oxidase and Cu, Zn superoxide dismutase. These mechanisms
      come into play in response to a high influx of Cu or during the course of normal
      Cu metabolism.

PMID- 10940337
TI  - Dietary regulation of intestinal gene expression.
AB  - We are becoming increasingly aware of inherited genetic abnormalities as causes
      of disease. However, alterations in gene expression can also contribute to other
      disease processes. Recently it has been suggested that our environment may alter
      such genes and thus be a direct influence on disease. Diet is a potent mechanism
      for altering the environment of cells of most organs, particularly the
      gastrointestinal tract. This review addresses the influence of nutritional
      factors on intestinal gene regulation. These influences include insulin, which is
      not a dietary component but responds to dietary changes, and butyrate, a short
      chain fatty acid produced by normal intestinal flora. Manipulation of diet may be
      a means of treating intestinal disorders. Nutritional treatment therefore is also
      discussed in the light of its effect on gene expression.

PMID- 10940338
TI  - Mitochondrial uncoupling proteins in energy expenditure.
AB  - Four recently discovered homologues of the brown adipose tissue-specific
      mitochondrial uncoupling protein (UCP1) vary from 29% to 58% in their similarity
      to UCP1. Although these homologues share important structural features with UCP1
      and like UCP1 can reduce the mitochondrial membrane potential when expressed in
      yeast, there is no clear evidence that they can function thermogenically in vivo.
      On the other hand, evidence continues to accumulate indicating that the up
      regulation of Ucp1 reduces excessive adiposity.

PMID- 10940339
TI  - Molecular mechanisms regulating hormone-sensitive lipase and lipolysis.
AB  - Hormone-sensitive lipase, the rate-limiting enzyme of intracellular TG
      hydrolysis, is a major determinant of fatty acid mobilization in adipose tissue
      as well as other tissues. It plays a pivotal role in lipid metabolism, overall
      energy homeostasis, and, presumably, cellular events involving fatty acid
      signaling. Detailed knowledge about its structure and regulation may provide
      information regarding the pathogenesis of such human diseases as obesity and
      diabetes and may generate concepts for new treatments of these diseases. The
      current review summarizes the recent advances with regard to hormone-sensitive
      lipase structure and molecular mechanisms involved in regulating its activity and
      lipolysis in general. A summary of the current knowledge regarding regulation of
      expression, potential involvement in lipid disorders, and role in tissues other
      than adipose tissue is also provided.

PMID- 10940340
TI  - ALCOHOL: its metabolism and interaction with nutrients.
AB  - In the past, alcoholic liver disease was attributed exclusively to dietary
      deficiencies, but experimental and judicious clinical studies have now
      established alcohol's hepatotoxicity. Despite an adequate diet, it can contribute
      to the entire spectrum of liver diseases, mainly by generating oxidative stress
      through its microsomal metabolism via cytochrome P4502E1 (CYP2E1). It also
      interferes with nutrient activation, resulting in changes in nutritional
      requirements. This is exemplified by methionine, one of the essential amino acids
      for humans, which needs to be activated to S-adenosylmethionine (SAMe), a process
      impaired by liver disease. Thus, SAMe rather than methionine is the compound that
      must be supplemented in the presence of significant liver disease. In baboons,
      SAMe attenuated mitochondrial lesions and replenished glutathione; it also
      significantly reduced mortality in patients with Child A or B cirrhosis.
      Similarly, decreased phosphatidylethanolamine methyltransferase activity is
      associated with alcoholic liver disease, resulting in phosphatidylcholine
      depletion and serious consequences for the integrity of membranes. This can be
      offset by polyenylphosphatidylcholine (PPC), a mixture of polyunsaturated
      phosphatidylcholines comprising dilinoleoylphosphatidylcholine (DLPC), which has
      high bioavailability. PPC (and DLPC) opposes major toxic effects of alcohol, with
      down-regulation of CYP2E1 and reduction of oxidative stress, deactivation of
      hepatic stellate cells, and increased collagenase activity, which in baboons,
      results in prevention of ethanol-induced septal fibrosis and cirrhosis.
      Corresponding clinical trials are ongoing.

PMID- 10940341
TI  - Fatty acids and immune responses--a new perspective in searching for clues to
      mechanism.
AB  - Dietary essential fatty acids are the precursors for eicosanoids. Among the
      eicosanoids derived from arachidonic acid, prostaglandin (PG) E2 is known to
      possess immunosuppressive actions. Thus, it has been a prevailing hypothesis that
      the immuno-modulatory roles of dietary fatty acids are mediated at least in part
      through the alteration of PG biosynthesis. PGs exert their biological effects
      through their cognate receptors. There are four subtypes of PGE receptors (EP1,
      EP2, EP3, and EP4) so far identified. Although the association of EP receptors
      with G proteins coupled to adenylate cyclase and the mobilization of
      intracellular calcium are well documented, downstream signaling pathways for
      these receptors are virtually unknown. Identification of downstream signaling
      pathways for each subtype of EP receptors and target genes regulated by the
      activation of the receptor will help with our understanding of the mechanism by
      which dietary fatty acids affect immune responses through the modulation of PGE2
      biosynthesis. Emerging evidence suggests that fatty acids can additionally act as
      second messengers, regulators of signal transducing molecules or transcription
      factors. Acylation with long-chain fatty acids can occur on a variety of
      signaling molecules and can affect their membrane translocation and functions.
      Dietary fatty acids can alter functional properties of lipid mediators by
      changing the composition of acyl moieties of these molecules. Evidence
      accumulated recently indicates that long-chain unsaturated fatty acids and their
      metabolites bind and activate peroxisome proliferator-activated receptors
      (PPARs). PPARs are nuclear hormone receptors and transcription factors that
      regulate the expression of broad arrays of genes involved not only in lipid and
      glucose metabolism, but also in immune and inflammatory responses. PPARs may
      therefore be important cellular targets that mediate modulation of immune
      responses by dietary fatty acids. Together, it becomes clear now that multiple
      steps in various receptor-mediated signaling pathways can be modulated by dietary
      fatty acids. It will be a challenging task to quantitatively determine how
      different fatty acids alter functional properties of multitude of signaling
      components and final cellular responses. Elucidating the mechanism of actions of
      fatty acids on receptor-mediated signaling pathways in immuno-competent cells
      will provide a new insight for understanding the immuno-modulatory roles of
      dietary fatty acids.

PMID- 10940342
TI  - Protein and amino acid metabolism during and after exercise and the effects of
      nutrition.
AB  - Sustained dynamic exercise stimulates amino acid oxidation, chiefly of the
      branched-chain amino acids, and ammonia production in proportion to exercise
      intensity; if the exercise is intense enough, there is a net loss of muscle
      protein (as a result of decreased protein synthesis, increased breakdown, or
      both); some of the amino acids are oxidized as fuel, whereas the rest provide
      substrates for gluconeogenesis and possibly for acid-based regulation. Protein
      balance is restored after exercise, but no hypertrophy occurs with habitual
      dynamic exercise. Resistance exercise causes little change in amino acid
      oxidation but probably depresses protein synthesis and elevates breakdown
      acutely. After exercise, protein synthesis rebounds for </=48 h, but breakdown
      remains elevated, and net positive balance is achieved only if amino acid
      availability is increased. There is no evidence that habitual exercise increases
      protein requirements; indeed protein metabolism may become more efficient as a
      result of training.

PMID- 10940343
TI  - Diet and apoptosis.
AB  - A range of compounds in or derived from the diet modulates apoptosis in cell
      cultures in vitro. These observations have important implications concerning the
      mechanisms whereby dietary components affect health. Proapoptotic compounds could
      protect against cancer by enhancing elimination of initiated, precancerous cells,
      and antiapoptotic compounds could promote tumor formation by inhibiting apoptosis
      in genetically damaged cells. Proapoptotic compounds could also contribute to age
      related degenerative diseases by activating cell death in postmitotic cells or
      shifting the normal balance of mitosis and apoptosis in tissues with regenerative
      capacity. Many age-related diseases, for example macular degeneration and
      Parkinson's disease, appear to have oxidative stress as an underlying component
      that interacts with genetic, dietary, and environmental factors to determine
      relative risk in an individual. Oxidative stress activates apoptosis, and
      antioxidants protect against apoptosis in vitro; thus, a central role of dietary
      antioxidants may be to protect against apoptosis. However, little in vivo data
      are available to directly link diet with altered apoptosis as an underlying
      determinant of disease. Moreover, the possible antagonistic effects of different
      dietary components and the uncertainty about whether proapoptotic compounds that
      may protect against cancer could contribute to degenerative diseases and vice
      versa indicate that there is a great need for better in vivo assessment of
      apoptosis and that caution should be exercised when extrapolating in vitro data
      on apoptosis to in vivo dietary recommendations.

PMID- 10940344
TI  - The extracellular Ca2+-sensing receptor: central mediator of systemic calcium
      homeostasis.
AB  - The cloning of the G protein-coupled, extracellular calcium (Ca(2+)o)-sensing
      receptor (CaR) has identified a central mediator of the mechanism governing
      systemic Ca(2+)o homeostasis. This system enables organisms to adapt successfully
      to wide variations in dietary Ca(2+)o intake while maintaining near constancy of
      Ca(2+)o. Whereas discussions of Ca(2+)o homeostasis have generally focused on the
      key role of Ca(2+)o-elicited changes in parathyroid hormone secretion, the
      presence of the CaRs in effector tissues of this system enables direct regulation
      of processes (e.g. renal tubular Ca(2+) reabsorption and possibly bone formation
      and resorption) that add additional layers of homeostatic control. As we
      understand more about how the CaR regulates these tissues, we may find that it
      participates in other processes relevant to mineral ion homeostasis, including
      the control of the 1-hydroxylation and activation of vitamin D3 or reabsorption
      of phosphate in the renal proximal tubule. Regardless, the remarkable sensitivity
      of the CaR to small changes in Ca(2+)o allows adjustments in the response of the
      Ca(2+)o homeostatic system to increases or decreases in the intake of dietary
      Ca(2+), for instance, that cause barely detectable alterations in Ca(2+)o.
      Furthermore, the CaR likely participates in coordinating interactions among
      several different homeostatic control systems (including those for water,
      Mg(2+)o, Na(+), extracellular volume, and/or blood pressure), despite the fact
      that these systems are often considered to function largely independently of
      mineral ion metabolism.

PMID- 10940345
TI  - Transcriptional control of adipogenesis.
AB  - The major transcriptional factors involved in the adipogenic process include
      proteins belonging to the CCAAT/enhancer binding protein family, peroxisome
      proliferator-activated receptor gamma, and adipocyte determination and
      differentiation dependent factor 1, also known as sterol regulatory element
      binding protein 1. This process has been characterized with the aid of cell lines
      that represent various stages in the path of adipocyte commitment, ranging from
      pluripotent mesodermal fibroblasts to preadipocytes. Molecular analyses have led
      to a cascade model for adipogenesis based on timed expression of CCAAT/enhancer
      binding proteins and peroxisome proliferator-activated receptor gamma. Gene
      targeting and transgenic-mouse technologies, which allow the manipulation of
      endogenous genes for these transcription factors, have also contributed to the
      understanding of adipogenesis. This review aims to integrate this information to
      gain an understanding of the transcriptional regulation of fat cell formation.

PMID- 10940346
TI  - The health benefits of wine.
AB  - Epidemiologic studies from numerous disparate populations reveal that individuals
      with the habit of daily moderate wine consumption enjoy significant reductions in
      all-cause and particularly cardiovascular mortality when compared with
      individuals who abstain or who drink alcohol to excess. Researchers are working
      to explain this observation in molecular and nutritional terms. Moderate ethanol
      intake from any type of beverage improves lipoprotein metabolism and lowers
      cardiovascular mortality risk. The question now is whether wine, particularly red
      wine with its abundant content of phenolic acids and polyphenols, confers
      additional health benefits. Discovering the nutritional properties of wine is a
      challenging task, which requires that the biological actions and bioavailability
      of the >200 individual phenolic compounds be documented and interpreted within
      the societal factors that stratify wine consumption and the myriad effects of
      alcohol alone. Further challenge arises because the health benefits of wine
      address the prevention of slowly developing diseases for which validated
      biomarkers are rare. Thus, although the benefits of the polyphenols from fruits
      and vegetables are increasingly accepted, consensus on wine is developing more
      slowly. Scientific research has demonstrated that the molecules present in grapes
      and in wine alter cellular metabolism and signaling, which is consistent
      mechanistically with reducing arterial disease. Future research must address
      specific mechanisms both of alcohol and of polyphenolic action and develop
      biomarkers of their role in disease prevention in individuals.

PMID- 10940347
TI  - Environment and contaminants in traditional food systems of northern indigenous
      peoples.
AB  - Traditional food resources of indigenous peoples are now recognized as containing
      a variety of environmental contaminants which reach food species through local or
      long-range transport avenues. In this chapter we review the published reports of
      contaminants contained in traditional food in northern North America and Europe
      as organochlorines, heavy metals, and radionuclides. Usually, multiple
      contaminants are contained in the same food species. Measurement of dietary
      exposure to these environmental contaminants is reviewed, as are major issues of
      risk assessment, evaluation, and management. The dilemma faced by indigenous
      peoples in weighing the multiple nutritional and socioeconomic benefits of
      traditional food use against risk of contaminants in culturally important food
      resources is described.

PMID- 10940348
TI  - Iron regulatory proteins and the molecular control of mammalian iron metabolism.
AB  - Mammalian iron homeostasis is maintained through the concerted action of sensory
      and regulatory networks that modulate the expression of proteins of iron
      metabolism at the transcriptional and/or post-transcriptional levels. Regulation
      of gene transcription provides critical developmental, cell cycle, and cell-type
      specific controls on iron metabolism. Post-transcriptional control through the
      action of iron regulatory protein 1 (IRP1) and IRP2 coordinate the use of
      messenger RNA-encoding proteins that are involved in the uptake, storage, and use
      of iron in all cells of the body. IRPs may also provide a link between iron
      availability and cellular citrate use. Multiple factors, including iron, nitric
      oxide, oxidative stress, phosphorylation, and hypoxia/reoxygenation, influence
      IRP function. Recent evidence indicates that there is diversity in the function
      of the IRP system with respect to the response of specific IRPs to the same
      effector, as well as the selectivity with which IRPs modulate the use of specific
      messenger RNA.

PMID- 10940349
TI  - The role of the microsomal triglygeride transfer protein in abetalipoproteinemia.
AB  - The microsomal triglyceride transfer protein (MTP) is a dimeric lipid transfer
      protein consisting of protein disulfide isomerase and a unique 97-kDa subunit. In
      vitro, MTP accelerates the transport of triglyceride, cholesteryl ester, and
      phospholipid between membranes. It was recently demonstrated that
      abetalipoproteinemia, a hereditary disease characterized as an inability to
      produce chylomicrons and very low-density lipoproteins in the intestine and
      liver, respectively, results from mutations in the gene encoding the 97-kDa
      subunit of the microsomal triglyceride transfer protein. Downstream effects
      resulting from this defect include malnutrition, very low plasma cholesterol and
      triglyceride levels, altered lipid and protein compositions of membranes and
      lipoprotein particles, and vitamin deficiencies. Unless treated,
      abetalipoproteinemic subjects develop gastrointestinal, neurological,
      ophthalmological, and hematological abnormalities.

PMID- 10940350
TI  - Oligosaccharides in human milk: structural, functional, and metabolic aspects.
AB  - Research on human milk oligosaccharides (HMOs) has received much attention in
      recent years. However, it started about a century ago with the observation that
      oligosaccharides might be growth factors for a so-called bifidus flora in breast
      fed infants and extends to the recent finding of cell adhesion molecules in human
      milk. The latter are involved in inflammatory events recognizing carbohydrate
      sequences that also can be found in human milk. The similarities between
      epithelial cell surface carbohydrates and oligosaccharides in human milk
      strengthen the idea that specific interactions of those oligosaccharides with
      pathogenic microorganisms do occur preventing the attachment of microbes to
      epithelial cells. HMOs may act as soluble receptors for different pathogens, thus
      increasing the resistance of breast-fed infants. However, we need to know more
      about the metabolism of oligosaccharides in the gastrointestinal tract. How far
      are oligosaccharides degraded by intestinal enzymes and does oligosaccharide
      processing (e.g. degradation, synthesis, and elongation of core structures) occur
      in intestinal epithelial cells? Further research on HMOs is certainly needed to
      increase our knowledge of infant nutrition as it is affected by complex
      oligosaccharides.

PMID- 10940351
TI  - Pathophysiology and therapeutic modification of thrombin generation in patients
      with coronary artery disease.
AB  - Thrombin plays a central role in thrombogenesis: it activates platelets, converts
      fibrinogen to fibrin, and activates factor XIII, which then crosslinks and
      stabilizes the fibrin clot. In addition, thrombin amplifies coagulation by
      activating factors VIII and V, key cofactors in the generation of activated
      factor X and thrombin, respectively. Even platelet function is influenced by
      thrombin. Hence, thrombin generation is most important both in the chronic
      progression of coronary atherosclerotic disease and in its conversion to acute
      events. To date, various therapeutic approaches capitalize on this knowledge by
      targeting specific thrombin-related pathways. Among the successful and carefully
      documented pharmacologic strategies in acute or chronic coronary heart disease
      are the use of unfractioned heparin, low-molecular-weight heparin, thrombolysis,
      hirudin, and/or inhibition of thrombin generation by glycoprotein IIb/IIIa
      antagonists, most often utilized on top of antiplatelet therapy (e.g., with
      acetylsalicylic acid) and/or vitamin K antagonism. The present review provides
      insights into the pathophysiology of thrombin generation in coronary
      atherosclerosis and gives an overview over the above mentioned therapeutic
      thrombin modifications.

PMID- 10940353
TI  - Ba(2+)-induced chromaffin cell death: cytoprotection by Ca(2+) channel
      antagonists.
AB  - Exposure of bovine adrenal medullary chromaffin cells to Ba(2+) ions (in the
      absence of Ca(2+) ions) caused their death, measured as lactate dehydrogenase
      (LDH) release. The concentration of Ba(2+) required to damage the cells by about
      65% ranged between 1 and 10 mM (no Ca(2+) added); the required exposure time was
      rather brief (15 min-4 h). The simultaneous presence of Ca(2+), Mg(2+) or Zn(2+)
      together with Ba(2+) (2 mM, 4 h) afforded cyprotection (60-80%). Individual
      selective blockers of Ca(2+) channel subtypes afforded no protection. However,
      combined nifedipine (3 microM) plus omega-conotoxin MVIIC (3 microM) offered full
      protection. Substantial protection was also seen with the "wide-spectrum" Ca(2+)
      channel blockers penfluridol (0.3 microM), lubeluzole (3 microM), dotarizine (3
      microM), flunarizine (3 microM), and mibefradil (3 microM). This protection was
      due to blockade of Ba(2+) entry through Ca(2+) channels because dotarizine (10
      microM) inhibited the increase in cytosolic [Ba(2+)] seen in fura-2-loaded
      chromaffin cells. Once Ba(2+) accumulated in the cytosol, it was not extruded by
      the Na(+)/Ca(2+) exchanger, as shown by the prolonged and sustained elevation of
      the fura-2 signal. This contrasts with the fast dissipation of the fura-2 signal
      generated by [Ca(2+)](i) elevation. Thus, Ba(2+) overload can cause cell death by
      mechanisms similar to those reported for Ca(2+) overload and might be used as a
      novel and convenient tool to search for new cytoprotective compounds.

PMID- 10940354
TI  - Neuroprotection produced by the NAALADase inhibitor 2-PMPA in rat cerebellar
      neurons.
AB  - The present study examined the neuroprotective actions of the N-acetylated-alpha
      linked-acidic dipeptidase (NAALADase) inhibitor 2-(phosphonomethyl)pentanedioic
      acid (2-PMPA) in four in vitro models of neurotoxicity. Using neuron-enriched
      primary cultures derived from rat embryo (E15) cerebellum, 2-PMPA afforded 100%
      neuroprotection from injuries induced by hypoxia (EC(50)=8.4 microM). In
      contrast, against glutamate or N-methyl-D-aspartate (NMDA) injury, 2-PMPA was
      less potent and its efficacy limited to a maximum of 46% and 16%, respectively. 2
      PMPA was not effective against veratridine-induced injury. Also, the less potent
      analog of 2-PMPA, 2-[phosphonomethyl]succinic acid (2-PMSA), was ineffective.
      Unlike 2-PMPA, the endogenous NAALADase substrate and mGlu(3) receptor agonist N
      acetyl-aspartyl-glutamate (NAAG) was neuroprotective against all four injury
      mechanisms and compared to 2-PMPA, exhibited a different "phosphate effect" on
      neuroprotection. These results confirm the superior efficacy of 2-PMPA to protect
      against injury caused by cellular anoxia, and are discussed relative to upstream
      modulation of hyperglutamatergic activity vs. downstream modulation of
      metabotropic receptors as possible targets for ischemia/stroke therapy.

PMID- 10940352
TI  - Lipopolysaccharide decreases bradykinin receptor-induced acidification responses
      in cultured bovine aortic endothelial cells.
AB  - The effects of bacterial lipopolysaccharide (Escherichia coli 0127-B8) on
      bradykinin receptor function in bovine aortic endothelial cells were investigated
      using a microphysiometer. Bradykinin and Lys(0)-desArg(10)-bradykinin produced
      concentration-dependent acidification responses with pEC(50) values of 8.87+/
      0.20 and 9.78+/-0.08, respectively. These responses were competitively and
      selectively antagonised by the bradykinin B(2) receptor antagonist, icatibant and
      the bradykinin B(1) receptor antagonist, desArg(9)-Leu(8)-bradykinin,
      respectively. The non-peptide bradykinin B(2) receptor antagonist, FR173657 (0.3
      and 3 nM), selectively antagonised bradykinin-induced acidification responses,
      causing rightward shifts of the concentration-response curves to bradykinin, but
      at the same time, significantly decreasing the maximum response. A preincubation
      with lipopolysaccharide (0.01 and 0.1 microg/ml) for 24 h caused a significant
      concentration-dependent decrease in maximal response to bradykinin (27.2+/-1.9
      and 9.7+/-0.4% of control) and the bradykinin B(1) receptor agonist, Lys(0)
      desArg(10)-bradykinin (59.0+/-7.14 and 25.3+/-7.8% of control), without affecting
      the EC(50). These results suggest that bradykinin B(1) receptors are
      constitutively expressed in cultured bovine aortic endothelial cells and that the
      microphysiometer provides a rapid, sensitive technique to characterise bradykinin
      receptors and investigate their regulation by cytokines. Interactions between
      bradykinin receptors and lipopolysaccharide may play a part in the cascade of
      deleterious effects that occur during septic shock.

PMID- 10940355
TI  - Comparative effects of dopamine D(1) and D(2) receptor antagonists on nerve
      growth factor protein induction.
AB  - We previously reported that following acute administration of haloperidol or (-)
      sulpiride, both dopamine D(2)-receptor antagonists, to mice induced nerve growth
      factor (NGF) gene expression, mediated by the interaction of c-fos with the AP-1
      binding site present in the first intron on the NGF gene. In contrast, the D(1)
      receptor antagonist R-(-)-8-chloro-2,3,4, 5-tetrahydro-3,1-methyl-5-phenyl-11-3
      benzyoepine-7-ol (SCH23390) did not induce NGF mRNA expression. We report here
      immunohistochemical and Western blot analyses showing that following injection of
      these drugs for 14 consecutive days, the amount of NGF protein increased
      gradually and was induced significantly in the hippocampus, piriform cortex,
      amygdala, dorsal striatum, and nucleus accumbens neurons. NGF enhances the
      release of acetylcholine from these regions. Cholinergic innervation in the
      striatum and nucleus accumbens neurons is believed to be related to late-onset
      extrapyramidal symptoms, while in the hippocampus and piriform cortex it is
      involved in enhancing cognition. Thus, our data suggest that haloperidol- and (-)
      sulpiride-induced NGF expression may be associated with both beneficial and
      adverse effects.

PMID- 10940357
TI  - Effect of dimethylsphingosine on muscarinic M(3) receptor signalling in SH-SY5Y
      cells.
AB  - The sphingosine kinase inhibitor, dimethylsphingosine, is an important tool for
      investigating intracellular effects of the putative second messenger compound,
      sphingosine 1-phosphate. However, the specificity of action of
      dimethylsphingosine has not been fully investigated. In human SH-SY5Y
      neuroblastoma cells, dimethylsphingosine (30 microM), produced a 25-fold increase
      in the EC(50) for methacholine-induced Ca(2+) mobilisation, and reduced the
      maximum response by 57+/-5%, suggesting the involvement of sphingosine 1
      phosphate production in the Ca(2+) signal. However, dimethylsphingosine also
      inhibited [3H]N-methylscopolamine binding to whole SH-SY5Y cells and reduced
      methacholine-induced phosphoinositide turnover. Thus, this compound must be used
      with caution when investigating the role of sphingosine kinase in G-protein
      coupled receptor-mediated Ca(2+) mobilisation responses.

PMID- 10940356
TI  - In vitro and in vivo pharmacological characterization of J-113397, a potent and
      selective non-peptidyl ORL1 receptor antagonist.
AB  - 1-[(3R,4R)-1-cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl -1, 3-dihydro
      2H-benzimidazol-2-one (J-113397) was found to be the first potent nonpeptidyl
      ORL1 receptor antagonist (K(i): cloned human ORL1=1.8 nM) with high selectivity
      over other opioid receptors (K(i): 1000 nM for human mu-opioid receptor, >10,000
      nM for human delta-opioid receptor, and 640 nM for human kappa-opioid receptor).
      In vitro, J-113397 inhibited nociceptin/orphanin FQ-stimulated [35S]guanosine 5'
      O-(gamma-thio)triphosphate (GTP gamma S) binding to Chinese Hamster Ovary (CHO)
      cells expressing ORL1 (CHO-ORL1) with an IC(50) value of 5.3 nM but had no effect
      on [35S]GTP gamma S binding by itself. Schild plot analysis of the [35S]GTP gamma
      S binding assay and cAMP assay using CHO-ORL1 indicated competitive antagonism of
      J-113397 on the ORL1 receptor. In CHO cells expressing mu-, delta- or kappa
      opioid receptors, J-113397 had no effects on [35S]GTP gamma S binding up to a
      concentration of 100 nM, indicating selective antagonism of the compound on the
      ORL1 receptor. In vivo, J-113397, when administered subcutaneously (s.c.), dose
      dependently inhibited hyperalgesia elicited by intracerebroventricular (i.c.v.)
      administration of nociceptin/orphanin FQ in a tail-flick test with mice. An in
      vitro binding study using mouse brains indicated that J-113397 possesses high
      affinity for the mouse ORL1 receptor (K(i): 1.1 nM) as well as the human
      receptor. In summary, J-113397 is the first potent, selective ORL1 receptor
      antagonist that may be useful in elucidating the physiological roles of
      nociceptin/orphanin FQ.

PMID- 10940358
TI  - Activation of transcription factors of nuclear factor kappa B, activator protein
      1 and octamer factors in hyperalgesia.
AB  - Involvement of c-fos and neuronal nitric oxide synthase (nNOS) in the
      hyperalgesia induced by complete Freund adjuvant (CFA) has been reported. In this
      paper, we attempted to investigate whether the transcription factors regulating
      the gene expression of c-fos and nNOS, including activator protein-1 (AP-1),
      nuclear factor kappa B (NF-kappa B), and octamer factors (Oct), are activated by
      CFA during the development of hyperalgesia. The electrophoretic mobility shift
      assay (EMSA) was used to determine whether there were changes in the
      transcription factors in the lumbar spinal cord of adult rats following
      subcutaneous injection of CFA in one hindpaw of the rats. Maximum binding of AP
      1, NF-kappa B and Oct was found at 0.5, 1 and 2 h after CFA injection,
      respectively. These findings suggest that the activation of these transcription
      factors is pivotal for the expression of c-Fos and nNOS proteins, which reached a
      peak at 3 and 48 h after CFA injection, respectively. The behavioral testing of
      hyperalgesia demonstrated that CFA reduced the thresholds for mechanical and
      thermal algesia, reaching a minimum at 6 h. The thresholds had only partially
      recovered after 96 h. Based on these findings, we conclude that AP-1, NF-kappa B
      and Oct are crucial for the expression of c-Fos proteins at an early stage (at 3
      h) and for the expression of nNOS at a late stage of hyperalgesia (48 h post
      injection) induced by CFA.

PMID- 10940361
TI  - Sex differences in forced-swim and open-field test behaviours after chronic
      administration of melatonin.
AB  - The effects of melatonin administered chronically on forced-swim test and open
      field test behaviours were examined in male and female rats. The forced-swim test
      has been shown to be sensitive to all major classes of antidepressants and
      evidence indicates that melatonin possesses putative antidepressive properties.
      Male and female Long-Evans rats received either a regimen of chronic
      administration of melatonin or the control condition for 14 days via the drinking
      water. On day 15, each animal was individually introduced into a swim chamber,
      and was scored for 15 min on the duration of swimming, struggling, and
      immobility. After 24 h, each animal was again tested in the forced-swim test for
      10 min. On day 18, all animals were tested in the open-field test apparatus for 5
      min. Results revealed that females consistently showed higher activity levels
      than males in the forced-swim and open-field tests. Melatonin significantly
      increased struggling in males on day 15, but failed to do so in females. Also,
      whereas melatonin-treated females showed higher levels of behavioural immobility
      during their first exposure to the forced-swim test, this effect was prevented
      upon a second exposure. In both males and females, melatonin decreased swimming
      in the forced-swim test while increasing open-field ambulatory behaviour.
      Therefore, it is unlikely that melatonin's mechanism of action is a general
      inhibitory effect on motor activity. Taken together, the results suggest that the
      effects of melatonin treatment on forced-swim test behaviours are sex- and test
      dependent.

PMID- 10940360
TI  - Mechanisms to prevent the toxicity of chronic neuroinflammation on forebrain
      cholinergic neurons.
AB  - Inflammatory processes may play an important role in the degeneration of basal
      forebrain cholinergic cells Alzheimer's disease. We infused the proinflammagen
      lipopolysaccharide into the basal forebrain of young rats and determined whether
      the chronic administration of two novel non-steroidal anti-inflammatory drugs or
      a pan-caspase synthesis inhibitor, z-Val-Ala-Asp(OMe)-fluoromethyl ketone (zVAD),
      could provide neuroprotection from the cytotoxic effects of the
      neuroinflammation. Chronic lipopolysaccharide infusions decreased choline
      acetyltransferase activity and increased the number of activated microglia within
      the basal forebrain region. The level of caspases 3, 8 and 9 was increased in
      ventral caudate/putamen. Non-steroidal anti-inflammatory drug therapy attenuated
      the toxicity of the inflammation upon cholinergic cells and reduced caspases 3, 8
      and 9 activity in the caudate/putamen. zVAD treatment significantly decreased the
      levels of caspases 3, 8 and 9 but did not provide neuroprotection for the
      cholinergic neurons. These results suggest that prostaglandins contribute to the
      degeneration of forebrain cholinergic neurons in Alzheimer's disease.

PMID- 10940362
TI  - Endothelial dysfunction accompanies a pro-oxidant, pro-diabetic challenge in the
      insulin resistant, obese Zucker rat in vivo.
AB  - We have recently made the novel observation that a pro-oxidant challenge with
      hydroquinone in combination with buthionine sulfoximine (each at 50 mg/kg i.p.
      daily for 7 days) provokes the onset of type II diabetes mellitus in a model of
      insulin resistance, the obese Zucker rat. Since endothelial dysfunction in
      oxidant stress may aggravate in vivo insulin resistance, we have now investigated
      endothelium-dependent and nitric oxide (NO)-mediated vascular responses in the
      obese Zucker rat in vivo following this pro-oxidant insult. Pro-oxidant-treated
      animals exhibited defective vasodepression to the endothelium-dependent agent
      acetylcholine and to a lesser extent, the NO donor glyceryl trinitrate, together
      with a reduction in circulating levels of cGMP. Our data therefore suggest that
      the progression to type II diabetes mellitus in the obese Zucker rat mediated by
      a pro-oxidant insult is associated with impairments in agonist-stimulated,
      endothelium-dependent vasodilation and vascular NO signalling.

PMID- 10940359
TI  - Local inhibitory effects of dynorphin A-(1-17) on capsaicin-induced thermal
      allodynia in rhesus monkeys.
AB  - Although dynorphin A-(1-17) has been characterized in vitro as a high efficacy
      kappa-opioid receptor agonist, functional studies of dynorphin A-(1-17) following
      central or systemic administration indicate the involvement of both opioid and
      non-opioid components. The aim of this study was to investigate whether local
      administration of dynorphin-related analogs can attenuate capsaicin (8-methyl-N
      vanillyl-6-nonenamide)-induced nociception and what type of opioid receptor
      mediates the local action of dynorphin A-(1-17) in monkeys. Capsaicin (100
      microg) was used to evoke a nociceptive response, thermal allodynia, which was
      manifested as a reduced tail-withdrawal latency in normally innocuous 46 degrees
      C warm water. Co-administration of dynorphin A-(1-17) (0.3-10 microg) with
      capsaicin in the tail dose-dependently inhibited thermal allodynia; however, both
      non-opioid fragments dynorphin A-(2-17) (10-300 microg) and dynorphin A-(2-13)
      (10-300 microg) were ineffective. Local antiallodynia of dynorphin A-(1-17) was
      antagonized by a small dose (100 microg) of an opioid receptor antagonist,
      quadazocine, applied s.c. in the tail. Pretreatment with a selective kappa-opioid
      receptor antagonist, nor-binaltorphimine (nor-BNI), s.c. 320 microg in the tail
      also reversed local antiallodynia of dynorphin A-(1-17). Both locally effective
      doses of antagonists, when applied s.c. in the back, did not antagonize local
      dynorphin A-(1-17), indicating that peripheral kappa-opioid receptors selectively
      mediated the local action of dynorphin A-(1-17) in the tail. In addition, a much
      larger dose of dynorphin A-(1-17) (1000 microg), when administered s. c. in the
      back or i.m. in the thigh, did not cause sedative or diuretic effects. These
      results suggest that in vivo opioid actions of dynorphin-related peptides can be
      differentiated locally in this procedure. They also indicate that local
      application of peptidic ligands may be a useful medication for localized pain.

PMID- 10940363
TI  - Hypoxia augments conversion of big-endothelin-1 and endothelin ET(B) receptor
      mediated actions in rat lungs.
AB  - We have examined the effect of endothelin-1, sarafotoxin-6C, big-endothelin-1 and
      other agents on perfused lungs from chronically hypoxic rats. Increases in
      pulmonary perfusion pressure induced by big-endothelin-1, endothelin-1,
      phenylephrine and potassium chloride were enhanced in hypoxic lungs, while the
      constrictor action of sarafotoxin-6C was not increased. When basal pulmonary
      perfusion pressure was raised, low doses of endothelin-1 and sarafotoxin-6C
      produced decreases in pulmonary perfusion pressure which were significantly
      greater in chronically hypoxic lungs, whereas responses to sodium nitroprusside
      were unchanged. Endothelin ET(B) receptor-mediated bronchoconstrictor responses
      were also potentiated in hypoxic lungs, whereas responses to carbachol were not.
      In hypoxic lungs, conversion of big-endothelin-1 to endothelin-1 was
      significantly increased. These data provide evidence for a generalised increase
      in vasomotor activity in chronically hypoxic lungs, and a more selective increase
      in endothelin ET(B) receptor-mediated vasodilator and bronchoconstrictor
      responses. Hypoxia also augments the conversion of big-endothelin-1 to endothelin
      1.

PMID- 10940364
TI  - The effect of the nitric oxide synthase inhibitor N-gamma-nitro-L-argine methyl
      ester on hypoxic pulmonary vasoconstriction.
AB  - We studied the role of nitric oxide in the regulation of pulmonary arterial tone
      and hypoxic pulmonary vasoconstriction. Rat pulmonary arteries (n=65,
      diameter=440+/-12 microm) were loaded to 17.5 mm Hg in a wire myograph and
      incubated with the nitric oxide synthase inhibitor N-gamma-nitro-L-argine methyl
      ester (L-NAME; 1, 10 or 100 microM) or distilled water (50 microl) prior to
      preconstriction with either 100 microM prostaglandin F(2 alpha) followed by
      acetylcholine (0.1-100 microM) or 5 microM prostaglandin F(2 alpha) followed by
      hypoxia. Concentrations of L-NAME (10 and 100 microM) which attenuated
      acetylcholine dilatation, elevated basal tone from 0. 2+/-0.5% to 9.4+/-2.1%
      (P<0.01) and 18.3+/-3.2% (P<0.001), respectively, potentiated contraction to 5
      microM prostaglandin F(2 alpha) from 35.9+/-3.1% to 56.2+/-6.8% (P<0.05) and
      66.4+/-5.8% (P<0.001), respectively, but had no significant effect on hypoxic
      pulmonary vasoconstriction. This suggests basal pulmonary nitric oxide release
      occurs, as well as in response to agonist-induced contraction, but not hypoxic
      pulmonary vasoconstriction.

PMID- 10940365
TI  - Role of gap junctions in endothelium-derived hyperpolarizing factor responses and
      mechanisms of K(+)-relaxation.
AB  - We have examined the effects of ouabain (1 mM), the gap junction inhibitors, 18
      alpha-glycyrrhetinic acid (100 microM), N-(piperidin-1-yl)-5-(4-chlorophenyl)-1
      (2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride
      (SR141716A; 10 microM) and palmitoleic acid (50 microM), and clotrimazole (10
      microM) against endothelium-derived hyperpolarizing factor (EDHF)-mediated and
      K(+)-induced vasorelaxations in the rat mesentery. In the presence of
      indomethacin (10 microM) and 300-microM N(G)nitro-L-arginine methyl ester (L
      NAME), carbachol caused EDHF-mediated relaxations (R(max)=85.3+/-4.0%). In the
      presence of ouabain, these responses were substantially reduced (R(max)=11.0+/
      2.3%). 18 alpha-glycyrrhetinic acid, SR141716A, palmitoleic acid and clotrimazole
      also significantly inhibited these EDHF-mediated responses. K(+) caused
      vasorelaxation of preparations perfused with K(+)-free buffer (R(max)=73.7+/
      2.4%), which were reduced by 10-microM indomethacin (R(max)=56.4+/-6.2%). K(+)
      vasorelaxation was essentially abolished by endothelial denudation. Both ouabain
      and 18 alpha-glycyrrhetinic acid opposed K(+) relaxations, however, neither
      SR141716A, clotrimazole nor palmitoleic acid had any effect. Direct cell-cell
      coupling via gap junctions was attenuated by ouabain, clotrimazole and
      palmitoleic acid. We conclude that: (i) that gap junctional communication plays a
      major role in EDHF-mediated relaxations, (ii) that K(+)-vasorelaxation is
      endothelium-dependent (thus, K(+) is unlikely to represent an EDHF), and (iii)
      that the inhibitory actions of ouabain and clotrimazole on gap junctions might
      contribute towards their effects against EDHF.

PMID- 10940366
TI  - Effects of pituitary adenylate cyclase activating polypeptide27 on cyclic AMP
      efflux and atrial dynamics in perfused beating atria.
AB  - Although pituitary adenylate cyclase activating polypeptide (PACAP) has been
      shown to increase cardiac force of contraction and to change the heart rate, the
      effect of PACAP on cyclic (c) AMP production in the atrium still has to be
      defined. In the present experiments, a simple protocol was developed for the
      evaluation of cAMP production in real-time base in the perfused beating left
      atria. The PACAP27-induced cAMP efflux in the atrial perfusate reflected changes
      in the production of cAMP in the atrial tissue. cAMP efflux was measured as an
      indicator of cAMP production in beating perfused rabbit atria. PACAP27 increased
      cAMP production in a dose- and time-dependent manner with a minor effect on
      atrial dynamics. These results suggest that PACAP27 has other roles besides
      control of force of contraction through cAMP production in the atrium.

PMID- 10940367
TI  - In vivo myocardial infarct size reduction by a caspase inhibitor administered
      after the onset of ischemia.
AB  - The aim of this study was to determine the effect of different administration
      protocols on the cardioprotective efficacy of the non-selective, irreversible
      caspase inhibitors N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk)
      and bocaspartyl-(OMe)-fluoromethylketone (BocD.fmk) in a rat in vivo ischemia and
      reperfusion paradigm. Hearts were made ischemic for 45 min and reperfused for 180
      min. Under these conditions, it was determined that zVAD.fmk was cardioprotective
      when administered before or after the onset of ischemia, whereas BocD.fmk was
      efficacious only when administered before the onset of ischemia. This is the
      first report of in vivo cardioprotection by a caspase inhibitor when administered
      after the onset of ischemia.

PMID- 10940368
TI  - Involvement of K(+) channel in procainamide-induced relaxation of bovine tracheal
      smooth muscle.
AB  - The relaxant effect of procainamide, a class Ia antiarrhythmic agent, was
      examined in bovine tracheal smooth muscle. Procainamide produced concentration
      dependent decreases in tension and full relaxation in the preparations contracted
      with methacholine (0.3 microM). By comparison, in preparations contracted with 40
      mM K(+), procainamide had only slight relaxant effects. The relaxant effects of
      cromakalim and salbutamol on 40 mM K(+)-contracted preparations were
      significantly (P<0.01) smaller than those on 0.3 microM methacholine-contracted
      ones. On the other hand, the concentration-response relationships for quinidine,
      lidocaine, mexiletine and propafenone were not so dramatically different between
      0.3 microM methacholine- and 40 mM K(+)-contracted preparations.
      Tetraethylammonium (300 microM), iberiotoxin (30 nM) and Ba(2+) (1 mM)
      significantly (P<0.05) attenuated the relaxant effects of procainamide on
      methacholine-induced contractions, whereas apamin (100 nM), 4-aminopyridine (300
      microM), and glibenclamide (10 microM) did not affect them. The inhibitory effect
      of a combination of iberiotoxin and Ba(2+) was greater than that of iberiotoxin
      or Ba(2+) alone (P<0.01). These results suggest that the activation of at least
      two types of K(+) (maxi-K(+) and inward rectifier K(+)) channels contributes to
      the procainamide-induced relaxation of bovine tracheal smooth muscle.

PMID- 10940369
TI  - An epithelial-derived factor inhibits contraction in canine perfused bronchial
      segments.
AB  - We have previously reported, using a novel preparation of canine airway segments,
      that the sensitivity of acetylcholine was greater when applied to the adventitial
      (outside) surface than the epithelial (inside) surface. The present study
      investigated if this "barrier-effect" was partly the result of pharmacological
      modulation by the epithelium. As previously demonstrated, canine airway segments
      were less sensitive to inside than outside application of acetylcholine (pD(2)
      3.0+/-0.4 and 4.5+/-0.4, respectively, P<0.001, n=5). The addition of donor
      bronchi significantly decreased the sensitivity of the airway segment to outside
      application of acetylcholine (pD(2) 4.3+/-0.2 and 3.6+/-0.2, respectively,
      P<0.002, n=4). Indomethacin (2.5 microM) treatment of both the donor bronchi and
      the airway segment and removal of donor epithelium abolished the rightward shift
      in the acetylcholine-response curves. In addition, inhibition of cyclooxygenase
      within the airway segments themselves, but not the donor bronchi, also inhibited
      the rightward shift in the curves. These results indicate that the donor
      epithelium is capable of pharmacologically modulating responses of the airway
      segment to outside applied acetylcholine by producing an epithelial-derived
      factor, which in turn causes the release of a downstream cyclooxygenase product
      from within the airway segment.

PMID- 10940370
TI  - Characterisation of muscarinic receptor subtypes in avian smooth muscle.
AB  - The identity of the muscarinic receptor subtype in the chick ileum was
      investigated in functional and binding studies. Preliminary studies [Choo, L.-K.,
      Mitchelson, F., Napier, P. 1988. J. Auton. Pharmacol. 8, 259-266] suggested
      apparent avian and mammalian family differences in the muscarinic receptor
      profile of ileal smooth muscle. In the current study, further characterisation
      was undertaken using a greater range of antagonists exhibiting high affinity for
      specific muscarinic receptor subtypes. Dissociation constants from functional and
      binding experiments were compared with published values for antagonists at each
      of the five muscarinic receptor subtypes. Linear regression and correlation
      analyses revealed the receptor initiating the contractile response was most
      likely of the muscarinic M(3) receptor subtype as the slope of the linear
      regression was 1.01+/-0.14 and the corresponding correlation coefficient (r) was
      0.95. The mammalian muscarinic M(5) receptor subtype also showed a high
      correlation with the data giving a slope of 0.89+/-0.27 and r value of 0.76.
      These findings were in direct contrast to those from binding experiments in which
      the single binding site detected was of the muscarinic M(2) receptor subtype. The
      slope of the linear regression was 1.14+/-0.24 with an r value of 0.87. Thus,
      these results suggest that there exists a high proportion of the muscarinic M(2)
      receptor subtype within the tissue that does not contribute to the functional
      response.

PMID- 10940371
TI  - Nociceptin inhibits capsaicin-induced bronchoconstriction in isolated guinea pig
      lung.
AB  - The isolated perfused guinea pig lung was used to investigate the effect of
      nociceptin against bronchoconstriction elicited by endogenous and exogenous
      tachykinins. The opioid receptor-like 1 (ORL1) receptor agonist,
      nociceptin/orphanin FQ (0.001-1 microM) produced a dose-related inhibition of the
      capsaicin-induced bronchoconstriction (10(-5)-10(3) microg) in isolated guinea
      pig lung (P<0.05), a response mediated by the release of endogenous tachykinins
      from lung sensory nerves. The new ORL1 receptor antagonist 1-[(3R, 4R)-1
      Cyclooctylmethyl-3-hydroxymethyl-4-piperidyl]-3-ethyl-1, 3-dihydro-2H
      benzimidazol-2-one (J-113397) (0.3 microM) significantly blocked the inhibitory
      effect of nociceptin/orphanin FQ (0.01 microM) on capsaicin-induced
      bronchoconstriction, whereas the non-selective opioid receptor antagonist
      naloxone (1 microM) had no effect. Nociceptin/orphanin FQ (1 microM) did not
      affect the bronchoconstriction induced exogenously by the tachykinin NK2 receptor
      agonist neurokinin A. In conclusion, the present data provide evidence that
      nociceptin inhibits capsaicin-evoked tachykinin release from sensory nerve
      terminals in guinea pig lung by a prejunctional mechanism. This inhibitory action
      occurs independently from activation of opioid receptors. The present study also
      indicates that J-113397 is a potent ORL1 receptor antagonist.

PMID- 10940372
TI  - Chymase mediates mast cell-induced angiogenesis in hamster sponge granulomas.
AB  - We investigated the contribution of mast cell chymase in mast cell-dependent
      angiogenesis using the hamster sponge-implant model, where angiogenesis in the
      granulation tissue surrounding the subcutaneously implanted sponge was evaluated
      by measuring the hemoglobin content. Daily local injection of compound 48/80 (3
      100 microg/site/day), a potent mast cell activator, induced formation of
      granulomas and angiogenesis in time- and dose-dependent manners. This angiogenic
      response was inhibited by chymase inhibitors including chymostatin (> or = 1
      nmol/site/day), soybean trypsin inhibitor (SBTI; > or = 1.4 nmol/site/day) and
      lima bean trypsin inhibitor (LBTI; > or = 3.3 nmol/site/day), but not by a
      tryptase inhibitor like leupeptin (> or = 700 nmol/site/day). Although pyrilamine
      (> or = 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine
      (300 microg/site/day) also inhibited angiogenesis, these effects were much less
      pronounced than those by chymase inhibitors. Furthermore, antigen-induced
      angiogenesis in hamsters pre-sensitized with ovalbumin was also inhibited by the
      chymase inhibitors by 60-70%. Our results suggest that chymase is a major
      mediator in mast cell-mediated angiogenesis.

PMID- 10940373
TI  - Interactions of pro-inflammatory and vasoactive mediators with nitric oxide in
      the regulation of rat vascular permeability during laparotomy.
AB  - Inhibition of constitutive nitric oxide (NO) synthases by administration of N(G)
      nitro-L-arginine methyl ester (L-NAME) during abdominal laparotomy provokes
      extensive vascular leakage in the rat gastrointestinal tract, assessed by the
      extravasation of [125I]human serum albumin. In the present study, the role of
      vasoactive or neutrophil-derived pro-inflammatory mediators in this process has
      been investigated. Administration of the thromboxane synthase inhibitor, 1-benzyl
      imidazole (BZI, 25-50 mg kg(-1), s.c.), the platelet-activating factor (PAF)
      receptor antagonist, 3-[4-(2-chlorophenyl)-9-methyl-6H-thienol-[3,2-f][1,2,4]
      triazolo- [4, 3-a][1,4]-diazepine-2-yl]-1-(4-morpholynil)-1-propionate (WEB 2086;
      0.5-1 mg kg(-1), s.c.), the 5-lipoxygenase synthase inhibitor, N-(4
      benzyloxybenzyl)-acetohydroxamic acid (BW A137C; 4-20 mg kg(-1), s.c.) or the
      vasopressin pressor receptor antagonist ([Mca(1),
      Tyr(Me)(2),Arg(8)]vasopressin/Manning peptide; 0.01-0.2 microg kg(-1), s.c.) dose
      dependently reduced the intestinal plasma leakage provoked by L-NAME (5 mg kg(
      1), s.c.), following a 5-cm abdominal laparotomy in anaesthetised rats. These
      findings suggest that constitutive NO synthase effectively counteracts the
      damaging actions on microvascular integrity of mediators, including thromboxanes,
      PAF, leukotrienes and vasopressin, released during surgical intervention.

PMID- 10940374
TI  - Effects of sodium tungstate on insulin and glucagon secretion in the perfused rat
      pancreas.
AB  - Both the direct effect of sodium tungstate on insulin and glucagon secretion in
      the perfused rat pancreas, and the insulin response to glucose and arginine in
      pancreases isolated from tungstate-pretreated rats were studied. Infusion of
      tungstate stimulated insulin output in a dose-dependent manner. The
      insulinotropic effect of tungstate was observed at normal (5.5 mM), and
      moderately high (9 mM) glucose concentrations, but not at a low glucose
      concentration (3.2 mM). Tungstate-induced insulin output was blocked by
      diazoxide, somatostatin, and amylin, suggesting several targets for tungstate at
      the B-cell secretory machinery. Glucagon release was not modified by tungstate.
      Pancreases from chronically tungstate-treated rats showed an enhanced response to
      glucose but not to arginine. Our results indicate that the reported reduction of
      glycemia caused by tungstate administration is, at least in part, due to its
      direct insulinotropic activity. Furthermore, chronic tungstate treatment may
      prime the B-cell, leading to over-response to a glucose stimulus.

PMID- 10940377
TI  - The respiratory complex I of bacteria, archaea and eukarya and its module common
      with membrane-bound multisubunit hydrogenases.
AB  - The proton-pumping NADH:ubiquinone oxidoreductase, also called complex I, is the
      first of the respiratory complexes providing the proton motive force which is
      essential for energy consuming processes like the synthesis of ATP. Homologues of
      this complex exist in bacteria, archaea, in mitochondria of eukaryotes and in
      chloroplasts of plants. The bacterial and mitochondrial complexes function as
      NADH dehydrogenase, while the archaeal complex works as F420H2 dehydrogenase. The
      electron donor of the cyanobacterial and plastidal complex is not yet known.
      Despite the different electron input sites, 11 polypeptides constitute the
      structural framework for proton translocation and quinone binding in the complex
      of all three domains of life. Six of them are also present in a family of
      membrane-bound multisubunit [NiFe] hydrogenases. It is discussed that they build
      a module for electron transfer coupled to proton translocation.

PMID- 10940375
TI  - beta-Funaltrexamine inactivates ORL1 receptors in BE(2)-C human neuroblastoma
      cells.
AB  - The potential interactions of natively expressed mu-opioid and opioid receptor
      like (ORL1) receptors were studied by exposing intact BE(2)-C cells to agonists
      or antagonists for 1 h. Pretreatment with the mu-opioid receptor agonist, [D
      Ala(2), N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), or the ORL1 receptor agonist,
      orphanin FQ/nociceptin desensitized both mu-opioid and ORL1 receptor responses.
      beta-Funaltrexamine (beta-FNA) pretreatment also blocked both mu-opioid and ORL1
      receptor responses, but only mu-opioid receptor binding was reduced. Moreover,
      beta-FNA (1 microM) failed to inhibit specific ORL1 receptor binding.

PMID- 10940376
TI  - Vasodilator effect of urotensin II, one of the most potent vasoconstricting
      factors, on rat coronary arteries.
AB  - The effects of human urotensin II on coronary flow were studied in the perfused
      rat heart. Urotensin II transiently decreased coronary flow, then induced
      sustained vasodilatation. In the presence of a cyclooxygenase inhibitor,
      diclofenac, coronary vasodilatation was significantly inhibited. A nitric oxide
      synthase inhibitor, N(G)-nitro-L-arginine (L-NNA), attenuated the urotensin
      induced vasodilatation. These data suggest that urotensin II modulates coronary
      flow through factors such as cyclooxygenase products and nitric oxide to elicit
      coronary vasodilatation.

PMID- 10940378
TI  - Antibacterial activities of temporin A analogs.
AB  - Temporin A (TA) is a small, basic, highly hydrophobic, antimicrobial peptide
      amide (FLPLIGRVLSGIL-NH2) found in the skin of the European red frog, Rana
      temporaria. It has variable antibiotic activities against a broad spectrum of
      microorganisms, including clinically important methicillin-sensitive and 
      resistant Staphylococcus aureus as well as vancomycin-resistant Enterococcus
      faecium strains. In this investigation the antimicrobial activity and structural
      characteristics of TA synthetic analogs were studied. For antibacterial activity
      against S. aureus and enterococcal strains, the hydrophobicity of the N-terminal
      amino acid of TA was found to be important as well as a positive charge at amino
      acid position 7, and bulky hydrophobic side chains at positions 5 and 12.
      Replacing isoleucine with leucine at amino acid positions 5 and 12 resulted in
      the greatest enhancement of antibacterial activity. In addition, there was little
      difference between the activities of TA and its all-D enantiomer, indicating that
      the peptide probably exerts its effect on bacteria via non-chiral interactions
      with membrane lipids.

PMID- 10940379
TI  - Single-channel analysis of a ClC-2-like chloride conductance in cultured rat
      cortical astrocytes.
AB  - The single-channel behavior of the hyperpolarization-activated, ClC-2-like
      inwardly rectifying Cl- current (IClh), induced by long-term dibutyryl-cyclic-AMP
      treated cultured cortical rat astrocytes, was analyzed with the patch-clamp
      technique. In outside-out patches in symmetrical 144 mM Cl-solutions, openings of
      hyperpolarization-activated small-conductance Cl channels revealed burst activity
      of two equidistant conductance levels of 3 and 6 pS. The unitary openings
      displayed slow activation kinetics. The probabilities of the closed and
      conducting states were consistent with a double-barrelled structure of the
      channel protein. These results suggest that the astrocytic ClC-2-like Cl- current
      Iclh is mediated by a small-conductance Cl channel, which has the same structural
      motif as the Cl- channel prototype CIC-0.

PMID- 10940381
TI  - High CO2-mediated down-regulation of photosynthetic gene transcripts is caused by
      accelerated leaf senescence rather than sugar accumulation.
AB  - The influence of elevated atmospheric CO2 on transcript levels of photosynthetic
      genes was investigated in leaves of Nicotiana tabacum cv. SamsunNN and cv.
      Wisconsin38 plants. Plants were grown under ambient (400 ppm) and elevated
      (800/1,000 ppm) atmospheric CO2, and transcript levels were determined in leaves
      of different age. Down-regulation of photosynthetic gene transcripts was apparent
      in senesing leaves only. A correlation between transcript levels and leaf
      contents of soluble sugars could not be found. To investigate whether a shift in
      leaf ontogeny would be involved in the regulation of photosynthetic genes
      transgenic tobacco plants expressing either the gus or ipt gene under control of
      the senescence-specific SAG-12 promoter [Gan, S. and Amasino, R.M. (1995) Science
      270, 1986-1988] were included in our studies. As expected SAG-12-driven GUS
      activity increased with leaf age. This increase of GUS activity was stimulated by
      elevated atmospheric CO2, accompanied by a loss of chlorophyll and the down
      regulation of photosynthetic genes, verifying that high CO2 accelerates leaf
      ontogeny. Senescence as well as down-regulation of photosynthetic genes could be
      delayed by ipt expression. Levels of soluble sugars were indistinguishable from
      wild type or even slightly elevated in ipt transgenic plants. Therefore, sugar
      accumulation as a cause for down-regulation of photosynthetic genes under high
      CO2 can be excluded. It appears more likely that the high CO2-mediated decline in
      photosynthetic gene transcripts is due to a temporal shift in leaf ontogeny.

PMID- 10940382
TI  - Nitric oxide protects Cu,Zn-superoxide dismutase from hydrogen peroxide-induced
      inactivation.
AB  - Reaction of Cu,Zn-superoxide dismutase (SOD1) and hydrogen peroxide generates a
      putative oxidant SOD-Cu2+-.OH that can inactivate the enzyme and oxidize 5,5'
      dimethyl-1-pyrroline-N-oxide (DMPO) to DMPO-.OH. In the presence of nitric oxide
      (.NO), the SOD1/H2O2 system is known to produce peroxynitrite (ONOO-). In
      contrast to the proposed cytotoxicity of .NO conferred by ONOO-, we report here a
      protective role of .NO in the H2O2-induced inactivation of SODI. In a dose
      dependent manner, .NO suppressed formation of DMPO-.OH and inactivation of the
      enzyme. Fragmentation of the enzyme was not affected by .NO. Bicarbonate retarded
      formation of ONOO-, suggesting that .NO competes with bicarbonate for the oxidant
      SOD-Cu2+-.OH. We propose that .NO protects SOD1 from H2O2-induced inactivation by
      reducing SOD-Cu2+.OH to the active SOD-Cu2+ with concomitant production of NO+
      which reacts with H2O2 to give ONOO-.

PMID- 10940380
TI  - High affinity insulin binding by soluble insulin receptor extracellular domain
      fused to a leucine zipper.
AB  - Insulin receptors (IRs) that are truncated at the end of the ectodomain form
      dimers that bind insulin with different characteristics to wild type receptors.
      These soluble IRs have lowered affinity for insulin compared with full-length IR,
      and exhibit linear Scatchard plots in contrast to the curvilinear plots obtained
      with full-length IR, IR truncated at the C-terminus of the transmembrane region
      and IR ectodomains fused to the self-associating constant domains from Fc or
      lambda immunoglobulins. In this report, we have fused the IR ectodomain to the 33
      residue leucine zipper from the transcriptional activator GCN4 of Saccharomyces
      cerevisiae. This fusion protein binds insulin with high affinity in a manner
      comparable to native receptor. The respective dissociation constants were Kd1 8.2
      X 10(-11) M and Kd2 1.6 x 10(-8) M for hIRedZip and Kd1 5.7 x 10(-11) M and Kd2
      6.3 x 10(-9) M for membrane-anchored, native receptor.

PMID- 10940383
TI  - A novel SCN5A mutation associated with idiopathic ventricular fibrillation
      without typical ECG findings of Brugada syndrome.
AB  - Mutations in the human cardiac Na+ channel alpha subunit gene (SCN5A) are
      responsible for Brugada syndrome, an idiopathic ventricular fibrillation (IVF)
      subgroup characterized by right bundle branch block and ST elevation on an
      electrocardiogram (ECG). However, the molecular basis of IVF in subgroups lacking
      these ECG findings has not been elucidated. We performed genetic screenings of
      Japanese IVF patients and found a novel SCN5A missense mutation (S1710L) in one
      symptomatic IVF patient that did not exhibit the typical Brugada ECG.
      Heterologously expressed S1710L channels showed marked acceleration in the
      current decay together with a large hyperpolarizing shift of steady-state
      inactivation and depolarizing shift of activation. These findings suggest that
      SCN5A is one of the responsible genes for IVF patients who do not show typical
      ECG manifestations of the Brugada syndrome.

PMID- 10940384
TI  - Mutations in the S4 domain of a pacemaker channel alter its voltage dependence.
AB  - In an attempt to study the functional role of the positively charged amino acids
      present in the S4 segment of hyperpolarization-activated cyclic nucleotide-gated
      cation (HCN) channels, we have introduced single and sequential amino acid
      replacements throughout this domain in the mouse type 2 HCN channel (mHCN2).
      Sequential neutralization of the first three positively charged amino acids
      resulted in cumulative shifts of the midpoint voltage activation constant towards
      more hyperpolarizing potentials. The contribution of each amino acid substitution
      was approximately -20 mV. Amino acid replacements to neutralize either the first
      (K291Q) or fourth (R300Q) positively charged amino acid resulted in the same
      shift (about 20 mV) towards more hyperpolarized potentials. Replacing the first
      positively charged amino acid with the negatively charged glutamic acid (K291E)
      produced a shift of approximately -50 mV in the same direction. None of the above
      amino acid substitutions had any measurable effect on the time course of channel
      activation. This suggests that the S4 domain of HCN channels critically controls
      the voltage dependence of channel opening but is not involved in regulating
      activation kinetics. No channel activity was detected in mutants with
      neutralization of the last six positively charged amino acids from the S4 domain,
      suggesting that these amino acids cannot be altered without impairing channel
      function.

PMID- 10940385
TI  - Functional properties of the R154X HNF-4alpha protein generated by a mutation
      associated with maturity-onset diabetes of the young, type 1.
AB  - Mutations in the hepatocyte nuclear factor 4alpha (HNF-4alpha) gene are
      associated with one form of maturity-onset diabetes of the young (MODY1). The
      R154X mutation generates a protein lacking the E-domain which is required for
      normal HNF-4alpha functions. Since pancreatic beta-cell dysfunction is a feature
      of MODY1 patients, we compared the functional properties of the R154X mutant in
      insulin-secreting pancreatic beta-cells and non-beta-cells. The R154X mutation
      did not affect nuclear localisation in beta-cells and non-beta-cells. However, it
      did lead to a greater impairment of HNF-4a function in beta-cells compared to non
      beta-cells, including a complete loss of transactivation activity and a dominant
      negative behaviour. .

PMID- 10940386
TI  - Annexin XI may be involved in Ca2+ - or GTP-gammaS-induced insulin secretion in
      the pancreatic beta-cell.
AB  - The aim of this study was to investigate possible involvement of annexin XI in
      the insulin secretory machinery. In fluorescence immunocytochemistry, annexin XI
      was found in the cytoplasm of pancreatic endocrine cells and a pancreatic beta
      cell line, MIN6, in a granular pattern. MIN6 cells also possessed weak and
      diffused annexin XI immunoreactivity in the cytoplasm. Immunoelectron microscopy
      revealed annexin XI in the insulin granules. Insulin secretion from streptolysin
      O-permeabilized MIN6 cells was inhibited by anti-annexin XI antibody, when the
      release was stimulated by either Ca2+ or GTP-gammaS, but not by a protein kinase
      C-activating phorbol ester. Inhibition of insulin release by anti-annexin XI
      antibody was reproduced in permeabilized rat islets. These findings suggest that
      annexin XI may be involved in the regulation of insulin secretion from the
      pancreatic beta-cells.

PMID- 10940387
TI  - Involvement of phospholipase D in store-operated calcium influx in vascular
      smooth muscle cells.
AB  - In non-excitable cells, sustained intracellular Ca2+ increase critically depends
      on influx of extracellular Ca2+. Such Ca2+ influx is thought to occur by a 'store
      operated' mechanism, i.e. the signal for Ca2+ entry is believed to result from
      the initial release of Ca2+ from inositol 1,4,5-trisphosphate-sensitive
      intracellular stores. Here we show that the depletion of cellular Ca2+ stores by
      thapsigargin or bradykinin is functionally linked to a phosphoinositide-specific
      phospholipase D (PLD) activity in cultured vascular smooth muscle cells (VSMC),
      and that phosphatidic acid formed via PLD enhances sustained calcium entry in
      this cell type. These results suggest a regulatory role for PLD in store-operated
      Ca2+ entry in VSMC.

PMID- 10940389
TI  - Regulation of the biosynthesis of acyl analogs of platelet-activating factor by
      purinergic agonist in endothlial cells.
AB  - We have previously shown that platelet-activating factor (PAF)-dependent
      transacetylase (TA) contains three catalytic activities, namely PAF:
      lysophospholipid TA (TAL), PAF: sphingosine TA (TAs) and PAF acetylhydrolase. It
      serves as a modifier of PAF actions by producing different lipid signal
      molecules. The TAL activity is involved in the biosynthesis of acyl analogs of
      PAF (acyl-PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine, acylacetyl-GPC) in
      agonist-stimulated endothelial cells. In the present investigation, we have
      studied the mechanism(s) by which the TA activity is regulated in ATP-treated
      endothelial cells. We have demonstrated that ATP, and thiol-modifying agents with
      ATP, specifically regulate only the TAL part of the TA activities.

PMID- 10940390
TI  - Autophosphorylation of the two C-terminal tyrosine residues Tyr1316 and Tyr1322
      modulates the activity of the insulin receptor kinase in vitro.
AB  - Previously, several studies have demonstrated that autophosphorylation of the C
      terminal tyrosine residues (Tyr1316 and Tyr1322) affects the signaling properties
      of the insulin receptor in vivo. To assess the biochemical consequences of the C
      terminal phosphorylation in vitro, we have constructed, purified and
      characterized 45 kDa soluble insulin receptor kinase domains (IRKD), either with
      (IRKD) or without (IRKD-Y2F) the two C-terminal tyrosine phosphorylation sites,
      respectively. According to HPLC phosphopeptide mapping, autophosphorylation of
      the three tyrosines in the activation loop of the IRKD-Y2F kinase (Tyr1146,
      Tyr1150, and Tyr1151) was not affected by the mutation. In addition, the Y2F
      mutation did not significantly change the Km values for exogenous substrates.
      However, the mutation in IRKD-Y2F resulted in a decrease in the maximum
      velocities of the phosphotransferase reaction in substrate phosphorylation
      reactions. Moreover, the exchange of the tyrosines in IRKD-Y2F led to an increase
      in the apparent Km values for ATP, suggesting a cross-talk of the C-terminus and
      the catalytic domain of the enzyme. In addition, as judged by size exclusion
      chromatography, conformational changes of the enzyme following
      autophosphorylation were abolished by the removal of the two C-terminal
      tyrosines. These data suggest a regulatory role of the two C-terminal
      phosphorylation sites in the phosphotransferase activity of the insulin receptor.

PMID- 10940388
TI  - Direct association of LIS1, the lissencephaly gene product, with a mammalian
      homologue of a fungal nuclear distribution protein, rNUDE.
AB  - LIS1 is a product of the causative gene for type I lissencephaly characterized by
      a smooth brain surface due to a defect in neuronal migration during brain
      development and a regulatory subunit of platelet-activating factor
      acetylhydrolase (PAF-AH). It is also a mammalian homologue of the fungal nuclear
      distribution (nud) gene, nudF, which controls the migration of fungal nuclei.
      Using the two-hybrid system, we identified a novel LIS1-interacting protein, rat
      NUDE (rNUDE), and found that it is a mammalian homologue of another fungal nud
      gene product, NUDE, and Xenopus mitotic phosphoprotein 43 which is phosphorylated
      in a cell cycle-dependent manner. rNUDE and the catalytic subunits of PAF-AH
      interact with the N- and C-termini of LIS1, respectively. However, these
      proteins, instead of simultaneously binding to LIS1, appeared to bind to LIS1 in
      a competitive manner. These results suggest that LIS1 functions in nuclear
      migration by interacting with multiple intracellular proteins in mammals.

PMID- 10940393
TI  - A model of bone adaptation as an optimization process.
AB  - The internal bone adaptation of the proximal femur is considered. A three
      dimensional finite element model of the proximal femur is used. The bone
      remodeling in this work is numerically described by an evolutionary remodeling
      scheme with anisotropic material parameters and time-dependent loading. The
      memory of past loading is included in the model to account for the delay in the
      bone response from the load changes. The remodeling rate equation is derived from
      the structural optimization task of maximizing the stiffness in each time step.
      Additional information can be extracted from the optimization process; the
      remodeling equilibrium parameter where no apposition or resorption takes place,
      is defined as the element optimality conditions and the optimal design is used as
      an initial design for the onset of the remodeling simulation. Two examples of
      bone adaptation resulting from load changes are given, and the irreversible
      nature of the model is illustrated.

PMID- 10940392
TI  - Isometric muscle length-tension curves do not predict angle-torque curves of
      human wrist in continuous active movements.
AB  - In this study we tested the hypothesis that during steady contractions of human
      wrist extensors or flexors, the torque-angle relationship during movements
      imposed about the wrist is predicted by the classical isometric muscle length
      tension curve, with ascending, descending and ascending limbs. Angle-torque
      relationships were measured during steady muscle activation (10% of maximal
      voluntary contraction: MVC), elicited either by electrical stimulation or
      voluntary regulation of the electromyogram (EMG). Flexion-extension movements of
      constant speed (+/-10 degrees /s) were imposed on the subjects' hands with a
      servo actuator, either through the full physiological range of motion +/-50
      degrees, or through +/-10 degrees. During extensor contractions, angle-torque
      curves in +/-50 degrees movements had ascending, descending and ascending limbs,
      as in isometric contractions. However, in +/-10 degrees movements, torque always
      increased with increasing muscle length and decreased with decreasing length,
      even over angles corresponding to the descending limb of isometric curves. For
      flexor activation, angle-torque curves had similar properties, though descending
      limbs were less obvious or absent. During imposed movements, hysteresis was
      observed in the angle-torque curves. This was attributed to non-linearities of
      the active muscles. Hysteresis reached a maximum at intermediate wrist angles and
      declined at maximal muscle length, contradicting the recent hypothesis that
      sarcomere non-uniformity is responsible for the hysteresis. We conclude that the
      classical isometric length-tension curve, with its prominent descending limb,
      does not predict angle-torque curves of human wrist muscles in continuous
      movements. A more appropriate model is one in which stiffness about the wrist is
      always positive and hysteresis is a significant factor.

PMID- 10940391
TI  - Involvement of an FtsH homologue in the assembly of functional photosystem I in
      the cyanobacterium Synechocystis sp. PCC 6803.
AB  - The Synechocystis sp. PCC 6803 genome encodes four putative homologues of the AAA
      protease FtsH, two of which (slr0228 and sll1463) have been subjected to
      insertional mutagenesis in this study. Disruption of sll1463 had no discernible
      effect but disruption of slr0228 caused a 60% reduction in the abundance of
      functional photosystem I, without affecting the cellular content of photosystem
      II or phycobilisomes. Fluorescence and immunoblotting analyses show reductions in
      PS I polypeptides and possible structural alterations in the residual PS I,
      indicating an important role for slr0228 in PS I biogenesis.

PMID- 10940394
TI  - Stability criterion for controlling standing in able-bodied subjects.
AB  - A new stability criterion that can be used to assess the standing condition of a
      subject from center of pressure (CoP) measurements is presented. This criterion
      can be applied, for example, to control a standing prosthesis, which should allow
      a paraplegic subject to stand up, sit down and stand safely without using hands
      for support. Experiments conducted with able-bodied subjects enabled us to
      establish a relationship between its stability and the subject's CoP position.
      Four CoP stability zones were identified: high preference, low preference,
      undesirable and unstable zones. The high preference zone is defined as the area
      where the CoP is found 99% of the time during quiet standing. The area where the
      CoP is found during the remaining 1% of the time is called the low preference
      zone. The undesirable zone is defined as the CoP area where the subject is forced
      to change posture in order to maintain balance, and the unstable zone is defined
      as the CoP area in which the subject is forced to step forward, backward or
      sideways to maintain stability. A general model of the proposed four stability
      zones was derived, which can be used to compute stability zones a priori for any
      subject and thus allows one to assess the subject's stability condition from the
      CoP measurements.

PMID- 10940395
TI  - Mechanical properties of brain tissue in-vivo: experiment and computer
      simulation.
AB  - Realistic computer simulation of neurosurgical procedures requires incorporation
      of the mechanical properties of brain tissue in the mathematical model. Possible
      applications of computer simulation of neurosurgery include non-rigid
      registration, virtual reality training and operation planning systems and robotic
      devices to perform minimally invasive brain surgery. A number of constitutive
      models of brain tissue, both single-phase and bi-phasic, have been proposed in
      recent years. The major deficiency of most of them, however, is the fact that
      they were identified using experimental data obtained in vitro and there is no
      certainty whether they can be applied in the realistic in vivo setting. In this
      paper we attempt to show that previously proposed by us hyper-viscoelastic
      constitutive model of brain tissue can be applied to simulating surgical
      procedures. An in vivo indentation experiment is described. The force
      displacement curve for the loading speed typical for surgical procedures is
      concave upward containing no linear portion from which a meaningful elastic
      modulus might be determined. In order to properly analyse experimental data, a
      three-dimensional, non-linear finite element model of the brain was developed.
      Magnetic resonance imaging techniques were used to obtain geometric information
      needed for the model. The shape of the force-displacement curve obtained using
      the numerical solution was very similar to the experimental one. The predicted
      forces were about 31% lower than those recorded during the experiment. Having in
      mind that the coefficients in the model had been identified based on experimental
      data obtained in vitro, and large variability of mechanical properties of
      biological tissues, such agreement can be considered as very good. By
      appropriately increasing material parameters describing instantaneous stiffness
      of the tissue one is able, without changing the structure of the model, to
      reproduce experimental curve almost perfectly. Numerical studies showed also that
      the linear, viscoelastic model of brain tissue is not appropriate for the
      modelling brain tissue deformation even for moderate strains.

PMID- 10940396
TI  - Effects of external trunk loads on lumbar spine stability.
AB  - Stability of the lumbar spine is an important factor in determining spinal
      response to sudden loading. Using two different methods, this study evaluated how
      various trunk load magnitudes and directions affect lumbar spine stability. The
      first method was a quick release procedure in which effective trunk stiffness and
      stability were calculated from trunk kinematic response to a resisted-force
      release. The second method combined trunk muscle EMG data with a biomechanical
      model to calculate lumbar spine stability. Twelve subjects were tested in trunk
      flexion, extension, and lateral bending under nine permutations of vertical and
      horizontal trunk loading. The vertical load values were set at 0, 20, and 40% of
      the subject's body weight (BW). The horizontal loads were 0, 10, and 20% of BW.
      Effective spine stability as obtained from quick release experimentation
      increased significantly (p<0.01) with increased vertical and horizontal loading.
      It ranged from 785 (S.D.=580) Nm/rad under no-load conditions to 2200 (S.D.=1015)
      Nm/rad when the maximum horizontal and vertical loads were applied to the trunk
      simultaneously. Stability of the lumbar spine achieved prior to force release and
      estimated from the biomechanical model explained approximately 50% of variance in
      the effective spine stability obtained from quick release trials in extension and
      lateral bending (0.53<R(2)<0.63). There was no such correlation in flexion
      trials. It was concluded that lumbar spine stability increased with increased
      trunk load magnitude to the extent that this load brought about an increase in
      trunk muscle activation. Indirectly, our data suggest that muscle reflex response
      to sudden loading can augment the lumbar spine stability level achieved
      immediately prior to the sudden loading event.

PMID- 10940397
TI  - Tibiocalcaneal kinematics of barefoot versus shod running.
AB  - Barefoot running kinematics has been described to vary considerably from shod
      running. However, previous investigations were typically based on externally
      mounted shoe and/or skin markers, which have been shown to overestimate skeletal
      movements. Thus, the purpose of this study was to compare calcaneal and tibial
      movements of barefoot versus shod running using skeletal markers. Intracortical
      bone pins with reflective marker triads were inserted under standard local
      anesthetic into the calcaneus and tibia of five healthy male subjects. The
      subjects ran barefoot, with a normal shoe, with three shoe soles and two orthotic
      modifications. The three-dimensional tibiocalcaneal rotations were determined
      using a joint coordinate system approach. Test variables were defined for
      eversion and tibial rotation. The results showed that the differences in bone
      movements between barefoot and shod running were small and unsystematic (mean
      effects being less than 2 degrees ) compared with the differences between the
      subjects (up to 10 degrees ). However, differences may occur during midstance
      when extreme shoe modifications (i.e. posterior orthosis) are used. It is
      concluded that calcaneal and tibial movement patterns do not differ substantially
      between barefoot and shod running, and that the effects of these interventions
      are subject specific. The result of this in vivo study contrasts with previous
      investigations using skin and shoe mounted markers and suggests that these
      discrepancies may be the result of the overestimation with externally mounted
      markers.

PMID- 10940398
TI  - Contributions of proximal and distal moments to axial tibial rotation during
      walking and running.
AB  - The purpose of this study was to determine the cause and effect relationship
      between tibial internal rotation and pronation of the foot during walking and
      heel-toe running. This would allow predictions of orthotic effectiveness in
      reducing knee pain related to excessive internal tibial rotation. Kinematic and
      force plate data were collected from twenty subjects performing ten running and
      ten walking trials across a force plate. Using a least-squares algorithm,
      attitude matrices for each segment in each frame were obtained and the angular
      velocity vector of the tibia was calculated. The intersegmental moment at the
      ankle was calculated from ground reaction force and kinematic data, and the power
      flow from foot to tibia associated with axial tibial rotation was calculated. In
      walking, all subjects exhibited a clear power flow from tibia to foot during most
      of the stance phase, indicating that the foot was following the body. This
      suggests that the use of foot orthoses to reduce knee pain associated with tibial
      rotation during walking will not be successful. During running, power flow was
      also mainly proximal to distal, but there were brief periods of opposite power
      flow. There was more variability between subjects during running, with five
      subjects having large distal to proximal power flow peaks. These observations may
      explain and support previous work that has found variable clinical effects of
      orthoses between patients.

PMID- 10940399
TI  - Analysis of human abnormal walking using a multi-body model: joint models for
      abnormal walking and walking aids to reduce compensatory action.
AB  - This paper proposes new models of diseased joints and evaluates the effectiveness
      of walking aids such as a cane and a brace for compensating for lost functions
      due to joint disorders. The ZMJ concept described in the previous work (Yamashita
      and Tagawa, 1988. In: Radharaman (Ed.), Robotics and Factories of the Future'87.
      Springer, New York, pp. 670-677) is modified into three joint models as follows:
      a passive element joint (PEJ) which has a spring at the diseased joint; a
      constrained range joint (CRJ), the motion of which stays within some constrained
      relative angle; a partial moment joint (PMJ) which can produce a partial amount
      of the moment produced about the joint in normal walking. A cane can enlarge a
      supporting area and adjust the posture of the upper torso to be upright. An
      ischial weight-bearing brace is effective for conservative management of hip
      disorders by reducing a load to the joint (Shiba et al., 1998. Clinical
      Orthopaedics and Related Research 351, 149-157). Walking aids like a cane or
      brace have been conveniently used by the handicapped. Abnormal walking was
      simulated for each joint model. Dynamic effects of a cane and a brace on abnormal
      walking were examined by the multi-body walking model.

PMID- 10940400
TI  - Squeeze-film lubrication of the human ankle joint with synovial fluid filtrated
      by articular cartilage with the superficial zone worn out.
AB  - A squeeze-film lubrication model of the human ankle joint in standing that takes
      into account the fluid transport across the articular surface is presented.
      Articular cartilage is a biphasic mixture of the ideal interstitial fluid and an
      elastic permeable isotropic homogeneous intrinsically incompressible matrix. The
      simple homogeneous model for articular cartilage models the case of early
      osteoarthritis, when the intact superficial zone of the normal articular
      cartilage, much stiffer in tension than the bulk material, has been already
      disrupted or worn out. The calculations indicate for this case that in normal
      approach motion the lubricating fluid film is quickly depleted and turned into a
      synovial gel film that is supposed to serve as a boundary lubricant if sliding
      motion follows

PMID- 10940401
TI  - Analytic analysis of the force sharing among synergistic muscles in one- and two
      degree-of-freedom models.
AB  - Mathematical optimization of specific cost functions has been used in theoretical
      models to calculate individual muscle forces. Measurements of individual muscle
      forces and force sharing among individual muscles show an intensity-dependent,
      non-linear behavior. It has been demonstrated that the force sharing between the
      cat Gastrocnemius, Plantaris and Soleus shows distinct loops that change
      orientation systematically depending on the intensity of the movement. The
      purpose of this study was to prove whether or not static, non-linear optimization
      could inherently predict force sharing loops between agonistic muscles. Using
      joint moment data from a step cycle of cat locomotion, the forces in three cat
      ankle plantar flexors (Gastrocnemius, Plantaris and Soleus) were calculated using
      two popular optimization algorithms and two musculo-skeletal models. The two
      musculo-skeletal models included a one-degree-of-freedom model that considered
      the ankle joint exclusively and a two-degree-of-freedom model that included the
      ankle and the knee joint. The main conclusion of this study was that solutions of
      the one-degree-of-freedom model do not guarantee force-sharing loops, but the two
      degree-of-freedom model predicts force-sharing loops independent of the specific
      values of the input parameters for the muscles and the musculo-skeletal geometry.
      The predicted force-sharing loops were found to be a direct result of the loops
      formed by the knee and ankle moments in a moment-moment graph.

PMID- 10940402
TI  - Active control of lateral balance in human walking.
AB  - We measured variability of foot placement during gait to test whether lateral
      balance must be actively controlled against dynamic instability. The hypothesis
      was developed using a simple dynamical model that can walk down a slight incline
      with a periodic gait resembling that of humans. This gait is entirely passive
      except that it requires active control for a single unstable mode, confined
      mainly to lateral motion. An especially efficient means of controlling this
      instability is to adjust lateral foot placement. We hypothesized that similar
      active feedback control is performed by humans, with fore-aft dynamics stabilized
      either passively or by very low-level control. The model predicts that
      uncertainty within the active feedback loop should result in variability in foot
      placement that is larger laterally than fore-aft. In addition, loss of sensory
      information such as by closing the eyes should result in larger increases in
      lateral variability. The control model also predicts a slight coupling between
      step width and length. We tested 15 young normal human subjects and found that
      lateral variability was 79% larger than fore-aft variability with eyes open, and
      a larger increase in lateral variability (53% vs. 21%) with eyes closed,
      consistent with the model's predictions. We also found that the coupling between
      lateral and fore-aft foot placements was consistent with a value of 0.13
      predicted by the control model. Our results imply that humans may harness passive
      dynamic properties of the limbs in the sagittal plane, but must provide
      significant active control in order to stabilize lateral motion.

PMID- 10940403
TI  - Alteration of patellofemoral contact during healing of canine patellar tendon
      after removal of its central third.
AB  - Alterations of the patellofemoral (PF) contact pressure and area were assessed
      using pressure-sensitive film after the removal of the central third of patellar
      tendon (PT) with healing over time in twelve dogs. The contralateral knee served
      as control. Histological sections were prepared for descriptive evaluation. No
      alterations in PT strain, PF contact pressure and area were measured immediately
      after the removal of the central third of PT compared with that before its
      removal. Compared with contralateral control, the healing of the donor PF induced
      a significantly increased PF contact area but not PF contact pressure in the
      specimens harvested at 6, 12, and 18 months after operation. Increased PF contact
      area indicated a proximal shift of the PF joint contact during flexion, which was
      associated with an increased strain of the healing PT under loading. The healing
      PT became hypertrophic compared with control, but the differences in the cross
      sectional area were reduced over time. Histologically, a poorly organized
      extracellular matrix was observed at 6 months, with a progressive improvement in
      collagen fiber alignment up to 18 months postoperatively. The results of this
      study suggest that the removal of the central third of PT does not immediately
      change PF contact pressure and areas. However, remodeling of the healing tendon
      may cause an elongated PT, resulting in an increase in PF contact area under a
      given quadriceps force by knee extension.

PMID- 10940404
TI  - In vivo human tendinous tissue stretch upon maximum muscle force generation.
AB  - In the present study, we examined the hypothesis that stretch of tendinous tissue
      in the human tibialis anterior (TA) muscle-tendon unit upon isometric
      dorsiflexion maximum voluntary contraction (MVC) varies along the entire
      tendinous component length. Ultrasound-based measurements of the excursions of
      the TA tendon origin and proximal end of the TA central aponeurosis were taken in
      the transition from rest to MVC in six men. Subtracting the TA tendon origin
      excursion from the excursion of the aponeurosis proximal end, the aponeurosis
      excursion was estimated. Estimation of the aponeurosis proximal region excursion
      was obtained subtracting the excursion of the insertion point of a central region
      fascicle on the aponeurosis from the whole aponeurosis excursion. Subtracting
      tendon excursion from the excursion of the central fascicle insertion point, the
      aponeurosis distal region excursion was estimated. Strain values were calculated
      dividing the excursions obtained by the original resting lengths. All excursions
      and lengths were measured in the mid-longitudinal axis of the TA muscle-tendon
      unit at the neutral anatomical ankle position. Tendon excursion and strain were
      0.5+/-0. 08 cm (mean+/-SE) and 3.1+/-0.2%, respectively. Aponeurosis excursion
      and strain were 1.1+/-0.15 cm and 6.5+/-0.6%, respectively. Aponeurosis distal
      region excursion and strain were 0.3+/-0.05 cm and 3.5+/-0.3%, respectively.
      Aponeurosis proximal region excursion and strain were 0.8+/-0.12 cm and 9.2+/-1%,
      respectively. Aponeurosis excursion and strain were larger by 110-120% (P<0.05)
      compared with tendon. Aponeurosis proximal region excursion and strain were
      larger by 165-170% (P<0.05) compared with aponeurosis distal region. These
      findings are in line with results from in vitro animal material testing and have
      important implications for theoretical models of muscle function.

PMID- 10940405
TI  - Mechanical behaviour modelling of balloon-expandable stents.
AB  - Endoprostheses are small struts placed by intravascular way to restore the
      vascular lumen and flow conditions. The purpose of this work is to provide models
      for evaluation and characterisation of some mechanical properties of a balloon
      expandable stent by using the finite element method. Here we present the results
      for a metallic tubular peripheral prosthesis: the P308 Palmaz stent. We focus on
      the mechanisms linked to the structure expansion and its long-term behaviour.
      Several models are constructed in order to determine the stent shape after
      dilation and to assess the stress and strain fields in its wall due to this
      transformation. They inform us about the shortening percentage on expansion,
      degrees of radial and longitudinal recoil, and weaknesses of the structure.
      Various methods, differing in their levels of complexity, are then attempted to
      exhibit the predominant factors responsible for the crushing of a stent under
      external pressure. Moreover, the sensitivity of this critical pressure to
      geometric imperfections is studied. Lastly, since this kind of material is
      implanted for a lifetime, we test the stent with regard to fatigue life. Beyond
      safety considerations, this type of characterisation provides mechanical
      properties that are often difficult to obtain by experiments. If it was available
      for various stents, such information could be used to choose the appropriate
      prosthesis for specific applications. Moreover, confronted with observations from
      practitioners, they might lead to a better understanding of the failure or
      success of a particular design and to work on the product optimisation.

PMID- 10940406
TI  - Interfacial conditions between a press-fit acetabular cup and bone during daily
      activities: implications for achieving bone in-growth.
AB  - Interfacial gaps and relative micromotions during activities are widely believed
      to restrict the boney in-growth process of non-cemented acetabular cups. Using
      finite element modeling of the cup-bone system, relative micromotions and
      interfacial gaps are calculated for walking slow, normal and fast and for
      climbing upstairs, downstairs and standing up from a chair. A 2mm press-fit is
      simulated and interfacial conditions in the immediate postoperative period (i.e.
      prior to boney in-growth) calculated between paired nodes covering the whole of
      the interface. In regions of 'safe' micromotions and 'allowable' gaps, boney in
      growth is simulated by specifying zero relative displacement between nodal pairs.
      The modified model is then resubjected to the loads associated with climbing
      upstairs, which was shown to be the worst activity. Interfacial conditions are
      recalculated for subsequent iterations. The procedure is repeated until no
      further in-growth is predicted. The final pattern of in-growth calculated with
      the model compares reasonably well with histological evidence from explanted
      canine cups (Cha et al., 1998. Transactions of the Orthopaedic Research Society,
      23, p. 373). Bridging between adjacent regions of in-growth is observed. Notably,
      in-growth occurs at most of the periphery but not in the polar region. The lack
      of polar in-growth is caused by the interfacial gap assumed to exist after cup
      implantation. It is suggested that increasing/decreasing hip-joint loads would
      have little effect on this lack of polar in-growth. However, excessive
      micromotions as a result of high hip-joint loads cause a lack of in-growth in the
      anterior region of the periphery in the model. Although such results were not
      found in the canine study, if relevant to the general human population, the
      avoidance of harsh weight-bearing activities may encourage complete peripheral in
      growth but is speculated to do little for polar in-growth.

PMID- 10940407
TI  - Effects of hip joint centre mislocation on gait analysis results.
AB  - Methods to determine the hip joint centre (HJC) location are necessary in gait
      analysis. It has been demonstrated that the methods proposed in the literature
      involve large mislocation errors. The choice should be made according to the
      extent by which HJC location errors distort the estimates of angles and resultant
      moments at the hip and knee joints. This study aimed at quantifying how
      mislocation errors propagate to these gait analysis results. Angles and moments
      at the hip and knee joint were calculated for five able-bodied subjects during
      level walking. The nominal position of the HJC was determined as the position of
      the pivot point of a 3D movement of the thigh relative to the pelvis. Angles and
      moments were then re-calculated after having added to HJC co-ordinates errors in
      the range of +/-30 mm. Angles and moments at both hip and knee joints were
      affected by HJC mislocation. The hip moments showed the largest propagation
      error: a 30 mm HJC anterior mislocation resulted in a propagated error into
      flexion/extension component of about -22%. The hip abduction/adduction moment was
      found the second largest affected quantity: a 30 mm lateral HJC mislocation
      produced a propagated error of about -15%. Finally, a 30 mm posterior HJC
      mislocation produced a delay of the flexion-to-extension timing in the order of
      25% of the stride duration. HJC estimation methods with minimum antero-posterior
      error should therefore be preferred.

PMID- 10940408
TI  - Experimental and computational approach for the evaluation of the biomechanical
      effects of dental bridge misfit.
AB  - Dental bridges supported by osseointegrated implants are commonly used to treat
      the partially or completely edentulous jaw. The bridges are manufactured in metal
      alloy using a sequence of technological steps which well match the requirement to
      get custom overstructures but does not guarantee geometrical and dimensional
      tolerances. Dentists often experience that a perfect fit of the bridge with the
      abutments is almost impossible to achieve. When a misfitting bridge is forced on
      the abutments, deformations may occur inducing a permanent preload at the fixture
      bone interface and the greater the misfit the greater is the preload and the risk
      of implant failure. This work gives an evaluation of the biomechanical effects
      induced by a misfitting bridge when forced on two supporting dental implants. The
      strains induced in the bridge have been measured using two purposely designed and
      fabricated experimental devices allowing different types of misfit. FEM 3D models
      of the bridge and of the bridge anchored to the bone by implants have been
      developed. The former has been validated by simulating the same loading
      conditions as in the experimental tests and comparing the bridge strains. Both
      models have been used for the evaluation of the stress induced in the bridge and
      at the fixture-bone interface by bridge length errors. The results show that the
      method may help to estimate the stress distribution in the bridge and bone as a
      consequence of different dental bridge misfits.

PMID- 10940409
TI  - Distinguishing fall activities from normal activities by velocity
      characteristics.
AB  - The purpose of this study was to identify unique features of the velocity profile
      during normal and abnormal (i.e., fall) activities so as to make the automatic
      detection of falls during the descending phase of a fall possible. Normal
      activities included walking, rising from a chair and sitting down, descending
      stairs, picking up an object from the floor, transferring in and out of a tub,
      and lying down on a bed. The fall activities included tripping, forward and
      backward falls from standing. The horizontal and vertical velocities (V(h) and
      V(v)) at various locations of the trunk was measured. It was found that the V(h)
      and V(v) of the trunk during normal activities were within a well-controlled
      range, and that when the velocity in one direction increased, the velocity in the
      other direction usually did not. In contrast, the V(h) and V(v) demonstrated two
      different characteristics for the fall movement. Firstly, the magnitude of both
      V(h) and V(v) of the trunk increased dramatically during the falling phase,
      reaching up to 2-3 times that of normal velocities. Secondly, the increase of
      V(h) and V(v) magnitude usually occurred simultaneously, and usually about 300
      400 ms before the end of the fall. These two velocity characteristics, that is,
      the magnitude change and the timing of the magnitude change of both V(h) and
      V(v), could be used to distinguish fall movements from normal activities during
      the descending phase of the fall. It is hoped that the application of these two
      velocity characteristics could lead to potentially preventing or degrading fall
      related injuries in the elderly population when connected with other devices.

PMID- 10940410
TI  - Theoretical study of intracellular stress fiber orientation under cyclic
      deformation.
AB  - We studied stress fiber orientation under a wide range of uniaxial cyclic
      deformations. We devised and validated a hypothesis consisting of two parts, as
      follows: (1) a stress fiber aligns to avoid a mechanical stimulus in the fiber
      direction under cyclic deformation. This means that, among all allowable
      directions, a stress fiber aligns in the direction which minimizes the stimulus,
      i. e., the summation of the changes in length of the stress fiber over one
      stretch cycle; and (2) there is a limit in the sensitivity of the cellular
      response to the mechanical stimulus. Due to this sensing limit, the orientation
      angle in stress fibers is distributed around the angle corresponding to the
      minimum stimulus. To validate this hypothesis, we approximated an anisotropic
      deformation of the membrane on which cells were to be cultured. We then obtained
      the relationships between the stretch range and the fiber angle in the undeformed
      state which minimize the mechanical stimuli, assuming that the membrane on which
      stress fibers and cells adhered was homogeneous and incompressible. Numerical
      simulation results showed that the proposed hypothesis described our previous
      experimental results well and was consistent with the experimental results in the
      literature. The simulation results, taking account of the second part of the
      hypothesis with a small value for the limit in sensitivity to the mechanical
      stimulus, could explain why cell orientation is distributed so widely with cyclic
      stretch ranges of <10%. The proposed hypothesis can be applied to various types
      of deformation because the mechanical stimulus is always sensed and accumulates
      under cyclic deformation without the necessity of a reference state to measure
      the stimulus.

PMID- 10940412
TI  - Modeling differences in the vibration response characteristics of the human body.
AB  - Mathematical models may provide a useful tool for the development and evaluation
      of seating systems for vibration mitigation. A five-degree-of-freedom (DOF) model
      was formulated based on the measured driving-point impedance and
      transmissibilities of major anatomical structures contributing to the observed
      resonance behaviors. The model was limited in its ability to simulate differences
      observed in the resonance behaviors of a broader population and was unable to
      simulate the multiple resonances observed in the thigh. This paper describes the
      effectiveness of a modified five DOF model in simulating the major resonance
      behaviors observed in the population using representative data from a 56 kg
      female and 75 kg male. In addition, the model was also evaluated for its ability
      to predict the effects of selected seat cushions. The modified lumped-parameter
      model improved the peak chest and spine transmissibility simulations. The model
      was effective in simulating both the lower impedance peak observed in the primary
      resonance region (4-8 Hz) and the prevalent impedance peak observed in the second
      resonance region (7-10 Hz) in the smaller subjects. However, the model was not
      effective in predicting the dampening observed in the second resonance peak with
      the use of cushions. Redistribution of the model coefficients for the legs and
      the consideration of coupling between the legs and other anatomical structures
      may further improve the ability of the lumped-parameter model to predict the
      effects of seating systems on vibration transmission in the human body.

PMID- 10940411
TI  - Indentation of an osteochondral repair: sensitivity to experimental variables and
      boundary conditions.
AB  - The sensitivity of the affects of indenter radius, defect depth, cartilage
      permeability and flow boundary conditions, on the indentation testing of a
      repairing osteochondral defect was investigated. Since the boundary condition on
      the flow across the cartilage repair-subchondral bone interface is not known, the
      effects of two different conditions were investigated: free-flow and no-flow. A
      poroelastic finite element model of an osteochondral defect at different stages
      of the repair process was developed using dimensions typical of the rabbit knee.
      Results showed when the radius of the indenter was much less than the thickness
      of the cartilage the sensitivity of the indentation displacement to flow boundary
      conditions decreased. Simulated indentation displacement was insensitive to bone
      regeneration up to 50% of the initial defect depth, which suggests that only the
      properties of the material in the upper-half of the defect are being evaluated.
      Small variations in permeability had little affect on the simulated indentation.
      In a fully repaired defect, the simulated indentation is independent of the
      boundary condition. However, while the defect is in the process of repair and the
      regenerated cartilage is deeper than the host, indentation is sensitive to the
      flow boundary condition. Based on these results, and feasible experimental
      conditions, we conclude that the boundary condition on the repair-subchondral
      bone interface must be known in all cases except when the defect approaches full
      repair, if accurate estimates of material properties are to be obtained from
      indentation.

PMID- 10940413
TI  - The open section effect in a long bone with a longitudinal defect - a theoretical
      modeling study.
AB  - A longitudinal defect dramatically alters the stress distribution within a long
      bone. The altered stress distribution can influence the structural properties of
      the bone and the stimulus for repair and remodeling of the defect and the
      surrounding bone. For applied torsion, the defect interrupts the normal shear
      flow around the bone. Reversal of the shear flow along the inner cortex of the
      bone is the primary characteristic of the "open-section" effect. Stress
      concentration effects also produce large stresses at the defect corners. A finite
      element model of a femur mid-diaphysis with a rectangular defect in the posterior
      cortex was developed to quantify the femur stress distribution and torsional
      stiffness for defect widths ranging from one-tenth of the femur outer diameter
      (0.1 OD) to 0.3 OD, and defect lengths ranging from 0.5 to 5 OD. Defects with a
      length of 1 OD or shorter had little influence on the femur torsional stiffness
      or the femur shear-stress distribution. The torsional stiffness decreased most
      dramatically as the defect length increased from 2 to 3 OD, but began to approach
      an asymptote near 5 OD. Shear flow reversal peaked at the center of the defect
      for defects longer than 1 OD, and the magnitude of the reversal began to approach
      an asymptote near 5 OD. For each defect, the largest stresses within the bone,
      developed at the defect corners. The results indicate that the open-section
      effect decreases the torsional stiffness and stress concentration effects
      decrease the torsional strength of a long bone with a longitudinal defect.

PMID- 10940414
TI  - A versatile shear and compression apparatus for mechanical stimulation of tissue
      culture explants.
AB  - We have developed an incubator housed, biaxial-tissue-loading device capable of
      applying axial deformations as small as 1 microm and sinusoidal rotations as
      small as 0.01 degrees. Axial resolution is 50 nm for applying sinewaves as low as
      10 microm (or 1% based on a 1 mm thickness) or as large as 100 microm. Rotational
      resolution is 0.0005 degrees. The machine is small enough (30 cm high x 25 cm x
      20 cm) to be placed in a standard incubator for long-term tissue culture loading
      studies. In metabolic studies described here, application of sinusoidal
      macroscopic shear deformation to articular cartilage explants resulted in a
      significant increase in the synthesis of proteoglycan and proteins (uptake of
      (35)S-sulfate and (3)H-proline) over controls held at the same static offset
      compression.

PMID- 10940416
TI  - In this issue ellipsis

PMID- 10940417
TI  - Recognizing major contributors

PMID- 10940415
TI  - Oblique scaling: an algorithm to correct for a non-perpendicular camera view in
      tendon strain measurements.
AB  - Image distortion due to a non-perpendicular camera view introduces serious errors
      in tendon and ligament strain measurements when data are recorded using a single
      camera. These errors can be corrected with the oblique scaling algorithm using
      two pairs of scaling markers attached to the tendon surface. Computer simulations
      show that application of this algorithm reduces errors over 100 times to less
      than 0.06%. The method is relatively insensitive to measurement errors in the
      scaling marker distance but sensitive to the accuracy of alignment of the scaling
      markers. It can be concluded that the oblique scaling algorithm eliminates the
      influences of a non-perpendicular camera view in single-camera tendon and
      ligament strain measurements.

PMID- 10940418
TI  - Treatment of ulnar neuropathy.

PMID- 10940419
TI  - Intracranial aneurysms and arterial hypertension: a review and hypothesis.
AB  - BACKGROUND: Intracranial aneurysms and systemic arterial hypertension coexist in
      a high percentage of patients. The relationship between intracranial aneurysms
      and hypertension is poorly defined. METHODS: Therefore, we reviewed the role of
      hypertension in the pathogenesis of saccular aneurysms as previously reported in
      clinical, experimental, and autopsy studies. RESULTS: Among 24 relevant clinical
      and/or autopsy studies, the mean incidence of pre-existing hypertension was 43.5%
      in aneurysm patients compared to 24.4% in the normal population. Although
      definitive evidence is lacking, data from multiple types of investigations
      indicate that systemic arterial hypertension creates a greater risk for the
      development of intracranial aneurysms than previously believed. The underlying
      pathophysiological mechanism(s) are also poorly defined. CONCLUSIONS: We propose
      a unifying hypothesis: Endothelial injury, occlusion of the vasa vasorum, and
      disruption of the synthesis of collagen and elastin are likely the most important
      factors in initiating the development of aneurysms. Chronic hypertension
      potentially affects all of these factors. Consequently, chronic hypertension may
      cause intimal thickening, necrosis of the tunica media, changes in the
      compositional matrix, and degeneration of the internal elastic lamina to develop
      in the arterial wall. These structural changes could cause a focal weakening in
      the arterial wall with resultant bulging. This theory accounts for the high
      incidence of intracranial aneurysms in the absence of any known associated
      hereditary or connective-tissue disease. Nor does it exclude the possibility of
      other etiological factors. From the perspective of prevention, however, it offers
      clear opportunities for prophylaxis.

PMID- 10940420
TI  - Giant aneurysm of the superficial temporal artery. Case report and review of the
      literature.

PMID- 10940421
TI  - Distal anterior choroidal artery aneurysm associated with an arteriovenous
      malformation. Intraoperative localization and treatment.
AB  - BACKGROUND: Distal anterior choroidal artery aneurysms are rare. The outcome of
      patients with distal anterior choroidal artery aneurysms has been poor, and the
      treatment of such aneurysms is surgically challenging. CASE DESCRIPTION: The
      authors describe the case of an 8-year-old girl with a ruptured distal anterior
      choroidal artery aneurysm associated with an arteriovenous malformation (AVM).
      The patient experienced sudden onset of headache and vomiting. Computed
      tomography revealed an intraventricular haemorrhage, and cerebral angiography
      demonstrated an aneurysm arising from the distal portion of the right anterior
      choroidal artery. The patient also had an AVM in the ipsilateral temporal lobe
      fed by the branches of the middle cerebral artery. A right frontotemporal
      craniotomy was performed with the aid of intraoperative angiography to eliminate
      both the AVM and the aneurysm. Intraoperative angiography was helpful in
      confirming the complete removal of the AVM and in accurate localization of the
      small and deeply placed distal anterior choroidal artery aneurysm. Both the AVM
      and the aneurysm were successfully treated and the patient was discharged without
      any neurological deficits. CONCLUSION: This case is the youngest reported patient
      with a distal anterior choroidal artery aneurysm. This report is also the first
      to describe an association of such an aneurysm with an AVM. The etiology of the
      aneurysm formation in this case and surgical strategy for deeply placed vascular
      lesions are discussed.

PMID- 10940422
TI  - Surgical resection of a cerebral arteriovenous malformation for treatment of
      superficial siderosis: case report.
AB  - BACKGROUND: To our knowledge, there are only two reported cases of cerebral
      arteriovenous malformation associated with superficial siderosis. In both cases,
      the patients were asymptomatic and were discovered on retrospective review of
      magnetic resonance imaging. CASE DESCRIPTION: We describe a case of superficial
      siderosis in a 47-year-old male with a remote history of closed head injury that
      presented with progressive hearing loss, cerebellar ataxia, and urinary
      incontinence. Lumbar puncture was indicative of active subarachnoid bleeding.
      Cerebral angiography revealed a small vascular malformation that was resected.
      RESULTS: Pathological examination confirmed the diagnosis of the arteriovenous
      malformation. Six months after surgery the patient is neurologically stable with
      no further progression of clinical signs or symptoms. CONCLUSIONS: We report the
      first case of surgical resection of an intracranial arteriovenous malformation
      for the treatment of superficial siderosis. We emphasize the necessity of a
      detailed evaluation when superficial siderosis is suspected to localize and
      resect potential bleeding sources, because the disease is progressive and often
      irreversible.

PMID- 10940423
TI  - Jugular bulb diverticulum associated with lower cranial nerve palsy and multiple
      aneurysms.
AB  - BACKGROUND: Jugular bulb diverticulum is a rare condition that has never been
      reported in association with lower cranial nerve palsy. CASE DESCRIPTION: A 54
      year-old woman developed acute swallowing disturbance and hoarseness.
      Neuroradiological examinations demonstrated a jugular bulb diverticulum as well
      as unruptured internal carotid and basilar tip aneurysms on the same side.
      Laboratory data for both serum and cerebrospinal fluid were normal. Steroids were
      given, and the cranial nerve palsy disappeared within 1 month. The aneurysms were
      successfully clipped. During the follow-up period of more than 1 year, the
      patient has done well and has no neurological deficit. CONCLUSION: This is the
      first reported case of jugular bulb diverticulum associated with a lower cranial
      nerve palsy and multiple aneurysms. We recommend close observation of patients
      with this condition regardless of its clinical presentation.

PMID- 10940424
TI  - Advanced image-guided skull base surgery.
AB  - BACKGROUND: Tumors of the skull base frequently encase or extend into normal
      neural and vascular structures. Preoperative planning and intraoperative
      identification of anatomic landmarks is especially important in complex tumors
      since it helps avoid or minimize surgical morbidity. METHODS: By creating a
      surgical plan the image guidance software offers help in the establishment of a
      surgical approach. During surgery, the neuronavigation system displays the
      location of anatomic landmarks of the skull base regardless of any erosion or
      displacement. RESULTS: A series of 10 patients with complex tumors in various
      skull base locations is reported. Osseous structures are easily identified using
      the CT-based image guidance since these landmarks do not shift due to CSF loss.
      Image fusion of CT and MRI data gives additional information on the displacement
      of soft tissue structures. Image fusion in a substraction mode is helpful when a
      tumor has invaded bony structures or when the encasement of major vessels has to
      be visualized. CONCLUSION: The preoperative data preparation (planning of the
      approach, image fusion) plays a vital role in modern neuronavigation and
      contributes useful information during surgery for complex skull base tumors. Such
      advanced neuronavigation increases the efficacy and safety of intraoperative
      maneuvers. Eroded and distorted anatomic landmarks are not subject to a
      significant amount of intraoperative shift throughout the surgical procedure.

PMID- 10940425
TI  - Diagnostic pitfalls in osteomyelitis of the odontoid process: case report.
AB  - BACKGROUND: Pyogenic osteomyelitis of the odontoid process is a very rare disease
      associated with a variety of clinical symptoms, and previous reports have
      stressed the difficulties inherent in making the diagnosis. The authors present a
      case of osteomyelitis of the odontoid process with epidural abscess in which
      magnetic resonance imaging (MRI) was used in the diagnosis, assessment of the
      extent of concomitant epidural abscess, treatment effect, and long-term follow
      up. CASE DESCRIPTION: A 68-year-old male was admitted to our hospital with
      cervical pain, neck stiffness, and fever. Although the diagnosis was missed at
      the beginning, the patient was diagnosed with osteomyelitis of the odontoid
      process with a paravertebral epidural abscess by MRI. The patient became
      asymptomatic after 3 months of antibiotic therapy. CONCLUSION: Pyogenic
      osteomyelitis of the odontoid process is a rare condition requiring a high index
      of suspicion for diagnosis. MRI examination should be considered in the diagnosis
      in patients with neck pain combined with fever. Serial MRI during and after
      antibiotic therapy provided an objective assessment of the healing rate of the
      lesions.

PMID- 10940426
TI  - Spinal chondrosarcoma following adenocarcinoma of the breast: case report.
AB  - BACKGROUND: Chest wall chondrosarcomas have been reported rarely in breast cancer
      patients treated with chest wall radiation therapy. However, there are no prior
      reports of spinal chondrosarcomas arising in patients with a history of breast
      adenocarcinoma. CASE DESCRIPTION: A neurologically intact 53-year-old woman with
      breast adenocarcinoma and new onset back pain was evaluated. Magnetic resonance
      imaging of the spine revealed a tumor of the posterior elements of T7, impinging
      upon the spinal cord. A computed tomography guided needle biopsy of the spinal
      mass failed to yield diagnostic results. The patient underwent an open surgical
      biopsy and complete excision of a low-grade chondrosarcoma. The patient's
      thoracic pain resolved after surgical excision of her thoracic tumor. She
      remained neurologically intact. Pathological examination of the tumor revealed a
      low-grade chondrosarcoma. CONCLUSION: We present the first reported case of
      chondrosarcoma of the spine arising in a patient with a history of breast
      adenocarcinoma without prior irradiation. Solitary spinal tumors in patients with
      breast adenocarcinoma should not be assumed to be metastatic lesions, and
      chondrosarcoma should be included in the differential diagnosis of spinal lesions
      in this patient population. Experimentally, chondrosarcomas have been shown to be
      sensitive to circulating levels of estrogens, and this might explain an
      association with adenocarcinoma of the breast treated with tamoxifen.

PMID- 10940427
TI  - Endodermal cyst of septum pellucidum and pregnancy: a case report.
AB  - BACKGROUND: Endodermal or Neurenteric cysts are commonly found in spine. Their
      intracranial occurrence is rare and such a cyst in the septum pellucidum is
      exceptional. METHOD: We report a woman, with 33 week pregnancy, presenting in a
      semiconscious state due to raised intracranial pressure (ICP) due to
      hydrocephalus caused by a large lesion in the septum pellucidum. Computed
      tomography (CT) revealed the lesion which was better characterised by the
      Magnetic Resonance Imaging (MRI). First baby was delivered by LSCS and bilateral
      ventriculo-peritoneal shunts were inserted; and later on the cyst was excised.
      RESULT: There was full neurological recovery following the insertion of VP shunt.
      After excision of cyst cerebrospinal fluid (CSF) pathway was established and
      shunts could be removed. Post-operative period was complicated by septic
      ventriculitis. Eventually patient was discharged home in excellent condition.
      CONCLUSION: Endodermal cyst of septum pellucidum is an uncommon condition. Such
      lesions may be large when revealed, good outcome is expected after surgical
      excision.

PMID- 10940429
TI  - Thoracic epidural lipomatosis with associated syrinx: case report.
AB  - A 54-year-old black male with a 15-year history progressive lower extremity
      weakness was evaluated with a thoracic MRI that revealed epidural lipomatosis
      extending from T1-T10 with an associated syrinx at T1-3. He was neither
      overweight nor taking steroids. A multilevel thoracic laminectomy with resection
      of lipoma was performed without directly addressing the syrinx. Postoperatively,
      his symptoms improved and an MRI obtained 1 year after surgery demonstrated
      resolution of the syrinx. This is the only case of epidural lipomatosis with an
      associated syrinx that we have seen reported in the world literature.

PMID- 10940428
TI  - Bilateral vocal cord paralysis after anterior cervical discoidectomy and fusion
      in a case of whiplash cervical spine injury: a case report.
AB  - BACKGROUND: Bilateral vocal cord paralysis is a risk of anterior cervical
      discoidectomy and fusion. We discuss the mechanism of vocal cord paralysis and
      the precautions necessary to avoid this catastrophic complication. A rare case of
      bilateral vocal cord paralysis after anterior cervical discoidectomy and fusion
      (ACD/F) is reported. CASE DESCRIPTION: The patient, a 37-year-old male, was
      paraplegic, had bilateral intrinsic hand muscle weakness and sphincter
      involvement following a whiplash cervical spinal injury. A C5-C6 ACD/F for
      traumatic C5-C6 disc prolapse was performed. On the third postoperative day, he
      developed difficulty in coughing and a husky voice. Otolaryngological evaluation
      revealed bilateral vocal cord paralysis. He later required a tracheostomy that
      partially alleviated his major symptoms. CONCLUSION: In patients undergoing
      ACD/F, a mandatory preoperative evaluation of the vocal cords should be
      performed. An appropriate modification in surgical planning should be made if
      vocal cord palsy is diagnosed preoperatively to prevent bilateral vocal cord
      paralysis. Proper and judicious use of Cloward retractors is advocated.

PMID- 10940431
TI  - Hematoma of the ligamentum flavum in the lumbar spine: case report.

PMID- 10940430
TI  - Ligament-sparing lumbar microdiscectomy: technical note.
AB  - BACKGROUND: The prevention or inhibition of postoperative adhesions is a
      significant goal for successful lumbar discectomy, not only to reduce the
      probable risk of recurrent radiculopathy, but also to improve the likelihood of
      success of re-operation. METHODS: We describe a new technique for sparing the
      ligamentum flavum in lumbar microdiscectomy. The superficial layer of the
      ligament is removed by horizontal splitting. Additional horizontal splitting of
      the ligament yields a paper-thin deep layer. Lateral vertical splitting and
      retraction is then carried out to provide a sufficient operative window. The
      split ligament returns to its original position after releasing the retraction,
      thereby closing the operative window. RESULTS: This method could preserve a layer
      of the ligamentum flavum to act as a physical barrier, which in turn greatly
      restricts the peridural fibrosis. CONCLUSIONS: This ligament-sparing technique
      enables surgeons to preserve the original anatomic plane and to reduce the extent
      of postoperative adhesion.

PMID- 10940432
TI  - Acute epidural hematoma developing during twist-drill craniostomy: a complication
      of percutaneous subdural tapping for the treatment of chronic subdural hematoma.
AB  - BACKGROUND: This case illustrates that although percutaneous subdural tapping for
      patients with chronic subdural hematoma (CSDH) is successful and minimally
      invasive, it can be complicated by acute epidural hematoma. CASE PRESENTATION: A
      62-year-old woman presented with headache two months after minor head trauma.
      Computed tomography (CT) scanning revealed CSDH with mixed density on the right
      side. Prior to percutaneous subdural tapping, twist-drill craniostomy was
      performed at the parietal tuber. When the drill-needle reached the dura mater,
      the patient began to complain of headache, which was followed by altered
      consciousness. CT scanning disclosed acute epidural hematoma abutting the CSDH;
      both hematomas were evacuated by emergency craniotomy. At surgery, no definite
      bleeding source was identified apart from oozing on the dura mater. CONCLUSION:
      Hemorrhagic complications after percutaneous subdural tapping are rare. The
      formation of acute epidural hematoma during twist-drill craniostomy has not been
      reported in the literature. This complication can occur when the blunt tip of the
      drill-needle remains on the dura mater without penetrating into the subdural
      hematoma cavity.

PMID- 10940433
TI  - Nocardia asteroides cerebral abscess in immunocompetent hosts: report of three
      cases and review of surgical recommendations.
AB  - BACKGROUND: Nocardia asteroides cerebral abscesses are rare intracranial lesions.
      They account for only 2% of brain abscesses. Existing literature takes the form
      of anecdotal reports, small case series, and retrospective studies. An optimal
      treatment approach has not been established. However, there is evidence that the
      size of the lesion and clinical and immune status of the patient are relevant to
      surgical decision making. METHODS: Three recent cases are presented and the
      existing literature is reviewed. RESULTS: The outcome in all three cases was
      satisfactory. Although the currently recommended neurosurgical management
      protocols were followed, one patient had a prolonged course, which may have been
      shortened had an earlier biopsy of the cerebral lesion been performed.
      CONCLUSIONS: The surgical approach to suspected Nocardia spp. cerebral abscesses
      has recently become less aggressive. A more aggressive approach than that
      currently preferred for suspected Nocardia spp. cerebral abscesses may be
      appropriate. Earlier biopsy of lesions to achieve specific identification and
      anti-microbial sensitivity profiles is suggested even in cases where an
      extracranial focus of infection is found. Delays in obtaining a biopsy may lead
      to non-specific or unhelpful results that may prolong the course in hospital and
      jeopardize the outcome.

PMID- 10940434
TI  - Encephalitis due to a free-living amoeba (Balamuthia mandrillaris): case report
      with literature review.
AB  - BACKGROUND: Amebic infections can spread to the central nervous system with a
      lengthy but usually fatal course. A typical case is presented to raise awareness
      of this increasingly reported infectious process that may have a more favorable
      outcome if diagnosed in its early stages. CASE DESCRIPTION: A 38-year-old male
      presented with an ulcerating 10 x 8 cm mass on his thigh and smaller skin
      nodules. In less than 6 months seizures developed due to granulomatous lesions of
      the brain. Biopsies/excisions of the thigh lesion, a subcutaneous nodule, and a
      brain lesion were performed. He failed to respond to broad spectrum antibiotics
      and antineoplastic agents, and died within 6 weeks of the initial MRI scan of the
      brain. Rare amebic trophozoites were appreciated in the biopsy specimens on post
      mortem review, and Balamuthia mandrillaris confirmed as the infecting agent on
      immunofluorescence studies. CONCLUSIONS: Granulomatous amebic encephalitis is a
      parasitic infection with a lengthy clinical course before rapid deterioration due
      to extensive brain lesions is noted. Either early treatment with antimicrobials
      or-in rare cases-excision of the brain lesion(s) may offer the chance of a cure.

PMID- 10940435
TI  - The CNS versus the AANS: who loses? You do!

PMID- 10940436
TI  - The eyes have it: the neuroethology, function and evolution of social gaze.
AB  - Gaze is an important component of social interaction. The function, evolution and
      neurobiology of gaze processing are therefore of interest to a number of
      researchers. This review discusses the evolutionary role of social gaze in
      vertebrates (focusing on primates), and a hypothesis that this role has changed
      substantially for primates compared to other animals. This change may have been
      driven by morphological changes to the face and eyes of primates, limitations in
      the facial anatomy of other vertebrates, changes in the ecology of the
      environment in which primates live, and a necessity to communicate information
      about the environment, emotional and mental states. The eyes represent different
      levels of signal value depending on the status, disposition and emotional state
      of the sender and receiver of such signals. There are regions in the monkey and
      human brain which contain neurons that respond selectively to faces, bodies and
      eye gaze. The ability to follow another individual's gaze direction is affected
      in individuals with autism and other psychopathological disorders, and after
      particular localized brain lesions. The hypothesis that gaze following is "hard
      wired" in the brain, and may be localized within a circuit linking the superior
      temporal sulcus, amygdala and orbitofrontal cortex is discussed.

PMID- 10940437
TI  - The ultimate resignation: suicide and search activity.
AB  - This paper presents an integrative approach to suicidal behavior in terms of
      search activity concept. Search activity concept displays a broad and holistic
      approach to behavior, adaptation to environment, body resistance, brain amine
      metabolism, and REM-sleep functions. Search activity is defined as activity that
      is oriented to change the situation (or at least the subject's attitude to it) in
      the absence of a precise prediction of the outcome of such activity, but taking
      into consideration outcomes at all previous stages of activity. According to the
      proposed hypothesis, renunciation of search (a state opposed to search activity)
      leads to a feeling of helplessness, problem-solution deficits, inefficient
      coping, dreams that represent renunciation of search, and a drop in the activity
      of amines. All these factors further exacerbate the state of renunciation of
      search and elevate suicidal risk. In addition, the remnants of search activity
      are misdirected to self-defeating behaviors that increase mental pain and
      contribute to renunciation of search. This hypothesis integrates findings from a
      number of fields of study of suicidal behavior, resolves some paradoxes, suggests
      new lines of research, and raises suggestions for assessment and treatment of
      suicidal behavior.

PMID- 10940438
TI  - The effects of hormones on sex differences in infection: from genes to behavior.
AB  - Males of many species are more susceptible than females to infections caused by
      parasites, fungi, bacteria, and viruses. One proximate cause of sex differences
      in infection is differences in endocrine-immune interactions. Specifically, males
      may be more susceptible to infection than females because sex steroids,
      specifically androgens in males and estrogens in females, modulate several
      aspects of host immunity. It is, however, becoming increasingly more apparent
      that in addition to affecting host immunity, sex steroid hormones alter genes and
      behaviors that influence susceptibility and resistance to infection. Thus, males
      may be more susceptible to infection than females not only because androgens
      reduce immunocompetence, but because sex steroid hormones affect disease
      resistance genes and behaviors that make males more susceptible to infection.
      Consideration of the cumulative effects of sex steroid hormones on susceptibility
      to infection may serve to clarify current discrepancies in the literature and
      offer alternative hypotheses to the view that sex steroid hormones only alter
      susceptibility to infection via changes in host immune function.

PMID- 10940439
TI  - Developmental and genetic audiogenic seizure models: behavior and biological
      substrates.
AB  - Audiogenic seizure (AGS) models of developmental or genetic origin manifest
      characteristic indices of generalized seizures such as clonus or tonus in
      rodents. Studies of seizure-resistant strains in which AGS is induced by intense
      sound exposure during postnatal development provide models in which other neural
      abnormalities are not introduced along with AGS susceptibility. A critical
      feature of all AGS models is the reduction of neural activity in the auditory
      pathways from deafness during development. The initiation and propagation of AGS
      activity relies upon hyperexcitability in the auditory system, particularly the
      inferior colliculus (IC) where bilateral lesions abolish AGS. GABAergic and
      glutaminergic mechanisms play crucial roles in AGS, as in temporal lobe models of
      epilepsy, and participate in AGS modulatory and efferent systems including the
      superior colliculus, substantia nigra, basal ganglia and structures of the
      reticular formation. Catecholamine and indolamine systems also influence AGS
      severity. AGS models are useful for elucidating the underlying mechanisms for
      formation and expression of generalized epileptic behaviors, and evaluating the
      efficacy of modern treatment strategies such as anticonvulsant medication and
      neural grafting.

PMID- 10940440
TI  - The role of the locus coeruleus in the development of Parkinson's disease.
AB  - In Parkinson's disease, together with the classic loss of dopamine neurons of the
      substantia nigra pars compacta, neuropathological studies and biochemical
      findings documented the occurrence of a concomitant significant cell death in the
      locus coeruleus. This review analyzes the latest data obtained from experimental
      parkinsonism indicating that, the loss of norepinephrine in Parkinson's disease
      might worsen the dopamine nigrostriatal damage. Within this latter context, basic
      research provided a new provocative hypothesis on the significance of locus
      coeruleus in conditioning the natural history of Parkinson's disease. In
      particular, the loss of a trophic influence of these neurons might be crucial in
      increasing the sensitivity of nigrostriatal dopamine axons to various neurotoxic
      insults. In line with this, recently, it has been shown that locus coeruleus
      activity plays a pivotal role in the expression of various immediate early genes
      and in inducing the phosphorilation of cyclic adenosine monophosphate response
      element-binding proteins, suggesting a role of the nucleus in sustaining a
      protective effect.

PMID- 10940441
TI  - Sex differences in the parental behavior of rodents.
AB  - The reproductive strategy of many mammalian species that give birth to altricial
      young involves intense and prolonged care of their offspring. In most cases, the
      mother provides all nurturance, but in some cases fathers, older siblings, or
      unrelated conspecifics participate in parental care. The display of these
      behaviors by animals other than mothers is affected by numerous factors,
      including their sex. We herein review the literature on similarities and/or
      differences between male and female laboratory rodents (rats, mice, voles,
      gerbils, and hamsters) in their parental responsiveness and discuss how the
      parental behavior of males and females is influenced by hormones, developmental
      processes, and prior social experiences. Understanding the mechanisms that
      generate sex differences in the parental responsiveness of rodents may indicate
      how similar sex differences in parental care are generated in other mammals.

PMID- 10940442
TI  - Gender differences in chronic major and double depression.
AB  - BACKGROUND: While the sex difference in prevalence rates of unipolar depression
      is well established, few studies have examined gender differences in clinical
      features of depression. Even less is known about gender differences in chronic
      forms of depression. METHODS: 235 male and 400 female outpatients with DSM-III-R
      chronic major depression or double depression (i.e., major depression
      superimposed on dysthymia) were administered an extensive battery of clinician
      rated and self-report measures. RESULTS: Women were less likely to be married and
      had a younger age at onset and greater family history of affective disorder
      compared to men. Symptom profile was similar in men and women, with the exception
      of more sleep changes, psychomotor retardation and anxiety/somatization in women.
      Women reported greater severity of illness and were more likely to have received
      previous treatment for depression with medications and/or psychotherapy. Greater
      functional impairment was noted by women in the area of marital adjustment, while
      men showed more work impairment. LIMITATIONS: Since our population consisted of
      patients enrolling in a clinical trial, study exclusion criteria may have
      affected gender-related differences found. CONCLUSIONS: Chronicity of depression
      appears to affect women more seriously than men, as manifested by an earlier age
      of onset, greater family history of affective disorders, greater symptom
      reporting, poorer social adjustment and poorer quality of life. These findings
      represent the largest study to date of gender differences in a population with
      chronic depressive conditions.

PMID- 10940443
TI  - Executive dysfunction predicts nonresponse to fluoxetine in major depression.
AB  - BACKGROUND: Functional brain imaging studies of major depression have
      consistently revealed hypometabolism or hypoperfusion in specific regions of the
      prefrontal cortex and basal ganglia. Studies of cognitive functioning in major
      depression have suggested that some but not all subjects exhibit cognitive
      deficits that are consistent with frontal-subcortical dysfunction, although the
      reasons for this heterogeneity are unclear. In this study, we explored this
      heterogeneity among depressed subjects by examining the relationship between
      cognitive functioning and treatment outcome. METHOD: Subjects with major
      depression were administered a complete neuropsychological test battery prior to
      treatment with fluoxetine. RESULTS: There were no significant differences between
      responders and nonresponders to fluoxetine in terms of age, educational
      achievement, number of past episodes of depression, and estimated premorbid IQ.
      However, nonresponders performed significantly worse than responders on several
      pretreatment measures of executive functioning, after controlling for baseline
      group differences in depression severity. LIMITATIONS: The results are based on a
      small sample of primarily female subjects, resulting in low statistical power and
      less generalizability to samples of male subjects with depression. CONCLUSIONS:
      The findings suggest that subtle prefrontal dysfunction in subjects with major
      depression may be predictive of poor response with particular medications.
      Assessment of the executive functions may play a particular role in pretreatment
      identification of subjects likely to respond to specific medications.

PMID- 10940444
TI  - MRI-based measurements of temporal lobe and ventricular structures in patients
      with bipolar I and bipolar II disorders.
AB  - OBJECTIVE: There have been relatively few quantitative MRI studies of temporal
      lobe structures and the lateral ventricles in bipolar patients and a lack of
      agreement across studies as to whether these structures differ significantly in
      size from control subjects. Also there have been no quantitative MRI studies of
      bipolar II patients. The present study measured temporal lobe and ventricular
      structures in both bipolar I and bipolar II patients, as well as control
      subjects. METHOD: Twenty-five bipolar I patients, 22 bipolar II patients and 19
      control subjects underwent MRI brain scans. The 5 mm coronal slices of each
      subject were coded and measured by a rater who was blind with respect to subject
      diagnosis. Volume estimates of the temporal lobe and hippocampus were calculated
      for each hemisphere by measuring the area of the structure in each slice in which
      it appears, multiplying by 5 mm and summing. In addition to these volume
      estimates, the area of the lateral ventricle and the inferior horn of the lateral
      ventricle, the lateral ventricle to cerebrum area ratio (LV/C) and the temporal
      lobe to cerebrum area ratio (TL/C), were calculated for each hemisphere in one
      reference slice only. The area of the third ventricle was also measured. Volume
      estimates and area ratios were then compared among diagnostic groups. RESULTS:
      There were no significant differences in temporal lobe or hippocampal volume
      estimates, in the third ventricle and inferior horn of the lateral ventricle area
      measurements, and in the TL/C area ratio among diagnostic groups. The lateral
      ventricle area and LV/C area ratio were significantly larger in bipolar I
      patients than either bipolar II patients or control subjects only in the left
      hemisphere. Furthermore, these measures were approximately twice as large in the
      bipolar I patients as the other groups. CONCLUSIONS: The current study adds to a
      growing literature that bipolar I disorder, particularly in males, may show
      different neurobiological alterations compared to bipolar II patients or control
      subjects. The pathophysiologic implications of this accumulating evidence of
      increased left ventricular size in bipolar I disorder remains to be further
      elucidated.

PMID- 10940445
TI  - Discrepancies between self and observer ratings of depression. The relationship
      to demographic, clinical and personality variables.
AB  - BACKGROUND: The observer-rated Hamilton depression scale (HamD) and the self
      report Beck Depression Inventory (BDI) are among the most commonly used rating
      scales for depression, and both have well demonstrated reliability and validity.
      However, many depressed subjects have discrepant scores on these two assessment
      methods. The present study evaluated the ability of demographic, clinical and
      personality factors to account for the discrepancies observed between BDI and
      HamD ratings. METHOD: The study group consisted of 94 SCID-diagnosed outpatients
      with a current major depressive disorder. Subjects were rated with the 21-item
      HamD and completed the BDI and the NEO-Five Factor Inventory. RESULTS: Younger
      age, higher educational attainment, and depressive subtype (atypical, non
      melancholic) were predictive of higher BDI scores relative to HamD observer
      ratings. In addition, high neuroticism, low extraversion and low agreeableness
      were associated with higher endorsement of depressive symptoms on the BDI
      relative to the HamD. In general, these predictive variables showed a greater
      ability to explain discrepancies between self and observer ratings of
      psychological symptoms of depression compared to somatic symptoms of depression.
      LIMITATIONS: The study does not determine which aspects of neuroticism and
      extraversion contribute to the observed BDI/HamD discrepancies. CONCLUSIONS:
      Depression ratings obtained with the BDI and HamD are frequently discordant and a
      number of patient characteristics robustly predict the discrepancy between these
      two rating methods. The value of multi-modal assessment in the conduct of
      research on depressive disorders is re-affirmed.

PMID- 10940446
TI  - Exploring aspects of DSM-IV interpersonal sensitivity in bipolar II.
AB  - BACKGROUND: The aim of the study was to find the prevalence of interpersonal
      rejection sensitivity (IRS) (a personality trait in DSM-IV) in bipolar II and
      unipolar depression. METHODS: 557 consecutive unipolar and bipolar II
      outpatients, presenting for depression treatment, were interviewed with the DSM
      IV Structured Clinical Interview and the Global Assessment of Functioning Scale.
      DSM-IV atypical features criteria (which include IRS) were followed. RESULTS: IRS
      was significantly more common in bipolar II than in unipolar patients (37.8% vs.
      20.5%, odds ratio 2.3, P=0.0000). Sensitivity and specificity for bipolar II
      diagnosis were 37.8% and 79.4%. CONCLUSIONS: IRS personality trait seems to be
      more common in bipolar II than in unipolar depression. LIMITATIONS: reliability
      of bipolar II diagnosis, non-blind, cross-sectional assessment, single
      interviewer.

PMID- 10940448
TI  - Personality and object relations in patients with affective disorders:
      idiographic research by means of the repertory grid technique.
AB  - BACKGROUND: This paper presents an idiographic approach to evaluate the self
      concept and the self-object-relationship of patients suffering from affective
      disorders. METHODS: Significant dimensions of the personality and the object
      relations of 127 depressive patients and 34 orthopaedic patients were
      investigated with the repertory grid-technique. The self concept and the object
      relations were compared by means of nomothetically used idiographic results after
      recovery from manifest depression. RESULTS: 'Low self esteem' was frequently
      found in patients with a long lasting course of illness and the ICD-10-diagnoses
      of 'bipolar affective disorder' and 'dysthymia'. The object relations of the
      depressive sample were characterised by the dimension 'symbiotic near';
      'ambivalent' and 'indifferent' partnership relationships were found much more
      frequently in the controls. CONCLUSIONS: The idiographic results help to
      differentiate the spectrum of affective disorders. They underline the importance
      of the interpersonal dimension of depression and may be used as a basis of a
      therapeutic appraisal. LIMITATIONS: The repertory grid-technique may not be used
      as a diagnostic instrument. However, the combination of idiographic results with
      further clinical informations enables the multidimensional assessment of the self
      concept and psychosocial coping mechanisms.

PMID- 10940447
TI  - The relationship between personality, dysfunctional parenting in childhood, and
      lifetime depression in a sample of employed Japanese adults.
AB  - BACKGROUND: Few studies have explored the relationship between personality,
      dysfunctional parenting in childhood, and adult depression. METHODS: Parental
      rearing styles and personality scores as measured by the Parental Bonding
      Instrument (PBI) and the Interpersonal Sensitivity Measure (IPSM) were compared
      in a group of employed Japanese adults with and without a lifetime history of
      depression. The diagnosis was provided by the Inventory to Diagnose Depression,
      Lifetime version (IDDL). To estimate the effects of the PBI and the IPSM scores
      on lifetime depression, a multiple logistic regression analysis was performed.
      RESULTS: Subjects with lifetime depression were seen to have significantly lower
      scores on the PBI 'care' and higher scores on the IPSM than the subjects without
      lifetime depression. Lower levels of maternal care and higher levels of
      'interpersonal sensitivity' each independently increased the risk for lifetime
      depression. LIMITATIONS: The findings of the present study may not be conclusive
      since the data were retrospectively obtained. CONCLUSION: Dysfunctional parenting
      and personality seem to be correlated by lifetime depression, but it is uncertain
      whether they are independent risk factors

PMID- 10940449
TI  - Social phobia: diagnosis and epidemiology, neurobiology and pharmacology,
      comorbidity and treatment.
AB  - Social phobia is a common disorder associated with significant psychosocial
      impairment, representing a substantial public health problem largely determined
      by the high prevalence, and the lifelong chronicity. Social phobia starts in
      early childhood or adolescence and is often comorbid with depression, other
      anxiety disorders, alcohol and substance abuse or eating disorders. This cascade
      of comorbidity, usually secondary to social phobia, increases the disability
      associated with the condition. The possibility that social phobia may be a
      trigger for later developing comorbid disorders directs attention to the need for
      early effective treatment as a preventive measure. The most recent drug class to
      be investigated for the psychopharmacological treatment of social phobia is the
      SSRI group for which there is growing support. The other drug classes that have
      been evaluated are monoamine oxidase inhibitors (MAOIs), benzodiazepines, and
      beta-blockers. The SSRIs represent a new and attractive therapeutic choice for
      patients with generalized social phobia. Recently the first, large scale, placebo
      controlled study to assess the efficacy of drug treatment in generalized social
      phobia has been completed with paroxetine. Paroxetine was more effective in
      reducing the symptoms than placebo and was well tolerated. Many now regard SSRIs
      as the drugs of choice in social phobia because of their effectiveness and
      because they avoid the problems of treatment with benzodiazepines or classical
      MAOIs.

PMID- 10940450
TI  - Roles of ion channels in EPSP integration at neuronal dendrites.
AB  - Many different kinds of voltage-gated ion channels (Na+ channels, K+ channels,
      Ca2+ channels) exist at neuronal dendrites. Integration of dendritic electric
      signals (excitatory postsynaptic potentials (EPSPs), inhibitory postsynaptic
      potentials (IPSPs) and action potentials) and/or non-electric signals (Ca2+ and
      second messengers) occurs in restricted dendritic compartments consisting of
      spines and adjacent fine dendrites. Voltage-gated ion channels at neuronal
      dendrites play crucial roles in the integration of dendritic signals. Dendritic
      signals, in turn, play important roles in the modulation of local dendritic
      physiological functions (e.g. input-specific synaptic plasticity, long-term
      potentiation (LTP) and long term depression (LTD)). A combined experimental and
      theoretical approach is a good way to clarify the biophysical behaviors of
      dendritic ion channels. Analyses of dendritic ion channels can open the door to a
      new wave of discoveries about EPSP integration at neuronal dendrites.

PMID- 10940451
TI  - In vitro and in vivo immunocytochemistry for the distribution of
      mineralocorticoid receptor with the use of specific antibody.
AB  - To examine the distribution of mineralocorticoid receptor (MR) and the
      interactions with glucocorticoid receptor (GR) in the brain, we raised a
      polyclonal antibody against the transcriptional modulation domain of rat MR using
      the GST-fusion system. Immunoblotting analysis revealed that this antibody
      recognized a band with the molecular mass of MR in MR-transfected COS-1 cells and
      in a homogenate of rat hippocampus, and showed no cross-reactivity with GR. In
      vitro immunocytochemistry of both primary cultured hippocampal neurons and MR
      transfected cells revealed immunoreactivity detected by this antibody in both the
      cytoplasm and nucleus in the absence of aldosterone (ALD), a specific agonist of
      MR. After 1 h of treatment with 10(-7) M ALD, the MR-immunoreactivity was
      accumulated in the nuclear region. In the case of GR-transfected cells, our anti
      MR antibody either detected no immunopositive cells in the presence or absence of
      GR agonist. In our in vivo study, MR-immunoreactivity was observed in the rat
      hippocampus, where cell nuclei showed immunopositive reactions. These results
      suggest that our antibody against rat MR shows high specificity for the receptor
      both in liganded and unliganded forms, with no cross-reactivity to GR, and will
      be useful for cell biological and neuroanatomical investigations of MR.

PMID- 10940452
TI  - Possible contribution of protein kinase C in the effects of histamine on the
      visceral nociceptor activities in vitro.
AB  - To clarify the possible contribution of protein kinase C activation in histamine
      induced excitation and sensitization of the heat response of testicular polymodal
      receptors, the effects of staurosporine, a protein kinase C inhibitor, and
      phorbol 12,13-dibutyrate, a protein kinase C activating phorbol ester, were
      studied in visceral polymodal receptors. Single polymodal receptor activities
      were recorded in vitro from testis-spermatic nerve preparations obtained from
      deeply anesthetized dogs (pentobarbital sodium, 30 mg/kg, i.v.). Histamine (10
      microM)-induced excitation and facilitation of the heat response of polymodal
      receptors were both suppressed by staurosporine (1 microM), suggesting that
      activation of protein kinase C is involved in both these effects of histamine.
      Application of phorbol 12,13-dibutyrate (0.1 microM) mixed with histamine
      increased the histamine-induced excitation, whereas a 5 min application of
      phorbol 12,13-dibutyrate before histamine suppressed it. These results suggest
      that phorbol 12,13-dibutyrate-activated protein kinase C has inactivation as well
      as activation effects on the intracellular cascade connected to histamine
      receptors, and that the former has a slower time course.

PMID- 10940453
TI  - Neuronal components of the superior and inferior tentacles in the terrestrial
      slug, Limax marginatus.
AB  - To identify the types of neurons and to infer the patterns of connectivity in
      slug tentacles, we stained the neurons in the superior and inferior tentacles in
      the terrestrial slug, Limax marginatus, by backfilling of the tentacular nerves
      with Lucifer yellow. Four types of stained neurons, '(1) sensory neurons', '(2)
      gamma cells', '(3) ganglion cells', '(4) lateral cells', were identified both in
      the superior and inferior tentacles. Three subtypes of the sensory neurons, '(1a)
      round sensory neurons', '(1b) spindle-shaped sensory neurons', and '(1c) small
      sensory neurons', were found in the digits. The gamma cells and the ganglion
      cells were interneurons. Three subtypes of gamma cells, '(2a) round monopolar
      gamma cells', '(2b) round bipolar gamma cells', and '(2c) large gamma cells',
      were present in the digits. The ganglion cells were composed of '(3a) monopolar
      ganglion cells', '(3b) bipolar ganglion cells', and '(3c) elongated ganglion
      cells'. The monopolar and bipolar types were located both in the tentacular
      ganglia and digits, whereas the elongated type was present only in the tentacular
      ganglia. The lateral cells, whose function is unknown, were found in the dermo
      muscular sheaths of the tentacles. Our study provides the first description of
      the neuronal map of inferior tentacles in gastropods. The results showed no
      differences in the morphological features of stained neurons between the superior
      and inferior tentacles in L. marginatus.

PMID- 10940454
TI  - Upregulation of synapsin IIa and IIb mRNAs in the paraventricular and supraoptic
      nuclei in chronic salt loaded and lactating rats.
AB  - The effects of chronic salt loading (2% saline to drink for 5 and 10 days),
      gestation, lactation and adrenalectomy on the expression of synapsin IIa and IIb
      genes were examined in the rat paraventricular (PVN) and supraoptic nuclei (SON),
      using in situ hybridization histochemistry. In each control, synapsin IIa and IIb
      genes were moderately expressed in the magnocellular division of the PVN and SON,
      while few transcripts of synapsin IIa and IIb were observed in the parvocellular
      division of the PVN. Chronic salt loading, gestation on day 21 and lactation on
      day 10 caused significant increases in synapsin IIa and IIb transcripts in the
      magnocellular division of the PVN and SON, compared to each control. Although
      corticotropin-releasing hormone transcripts in the parvocellular division of the
      PVN were significantly increased in the adrenalectomized rats, no changes in the
      transcripts of synapsin IIa and IIb were observed throughout the PVN. These
      results suggest that physiological stimuli such as osmotic challenge and
      lactation potently increase synapsin IIa and IIb mRNAs in the magnocellular
      neurons of the PVN and SON.

PMID- 10940455
TI  - A triphasic curve characterizes the retention of lever-pressing behavior rewarded
      by lateral hypothalamic stimulation during the immediate-post-trial period in
      rats: implications for a transient-intermediate stage between short- and long
      term memory.
AB  - We investigated the retention of lever-pressing behavior in rats rewarded by
      lateral hypothalamic (LHT) stimulation. Rats with electrodes implanted into the
      lateral hypothalamus were trained to press a lever to receive LHT stimulation.
      More than 90% of rats which had self-stimulated for longer than 30 min retained
      this behavior when tested 1 or 7 days later, indicating that intracranial self
      stimulation (ICSS) produced a stable long-term memory lasting for at least 7
      days. Subsequently, we examined retention at shorter ICSS-test intervals.
      Retention rates were measured 15, 30, 60, 90, 120, 180 or 360 min after the end
      of a 90-min period of ICSS, using a different group of 15 rats for each interval.
      Unexpectedly, retention rates in shorter interval tests were lower than those
      observed after 1 or 7 days. We observed a characteristic fluctuation in retention
      rates with lower rates at 30 and 180 min, giving a triphasic form to the
      retention curve with peaks at 15, 90 and 360 min. When a group of rats that had
      been previously stimulated and shown to have retained the lever-pressing behavior
      was allowed to re-stimulate a second time, no fluctuations were observed in short
      term interval tests. This indicates that the fluctuations in the retention curve
      immediately after initial ICSS are closely related to the initial acquisition of
      the memory. Our results support a three-phase model of memory formation that
      includes a transient-intermediate stage between short- and long-term memory.

PMID- 10940456
TI  - Acute responses of renal nerve activity to microgravity induced by free drop in
      anesthetized rats.
AB  - To examine acute cardiovascular and autonomic responses to microgravity (microG),
      arterial pressure (AP), aortic flow velocity (AFV), central venous pressure
      (CVP), and renal nerve activity (RNA) were measured in anesthetized rats during
      4.5 s of microG produced by free drop. A smooth and immediate reduction in
      gravity occurred during free drop, microG being achieved 100 ms after the start
      of the drop. Acute microG elicited an immediate and striking, but transient,
      decrease in RNA with no significant change in AP and AFV, but a significant
      decrease in CVP. The decrease in RNA lasted 2 s, then RNA recovered to the
      control level despite the G value remaining at < 0.001 for 4.5 s. The RNA
      decrease was attenuated or completely abolished by sinoaortic denervation,
      vagotomy, or sinoaortic denervation plus vagotomy. These results suggest that
      acute microG conditions stimulate sinoaortic and cardiopulmonary mechanoreceptors
      and suppress RNA.

PMID- 10940457
TI  - Oxidative glutamate toxicity involves mitochondrial dysfunction and perturbation
      of intracellular Ca2+ homeostasis.
AB  - Glutamate toxicity on PC12 cells is mediated by oxidative stress as a consequence
      of the inhibition of a cystine uptake system with depletion of GSH. In this study
      we report that glutamate decreases PC12 cell viability, inhibiting the reduction
      of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). This
      decrease was prevented by the antioxidants vitamin E, idebenone and L-deprenyl,
      which were also shown to be effective in reducing the accumulation of reactive
      oxygen species (ROS) in cells exposed to glutamate, decreasing the fluorescence
      of 2',7'-dichlorofluorescein (DCF). Incubation of PC12 cells with high glutamate
      concentrations induced mitochondrial dysfunction, leading to the loss of
      mitochondrial transmembrane potential, evaluated as a decrease in rhodamine 123
      (Rh123) retention by mitochondria, and to the decrease of intracellular ATP
      levels. The mitochondrial dysfunction, induced by glutamate, can be involved in
      the observed increase of [Ca2+]i. The elevation of [Ca2+]i occurred after GSH
      depletion, suggesting that oxidative stress is involved in the disturbances of
      intracellular calcium homeostasis. In conclusion, our data indicate that
      glutamate, at concentrations which block cystine uptake in PC12 cells leading to
      GSH depletion and inducing oxidative stress, increases ROS accumulation and
      decreases cell survival by a mechanism involving mitochondrial dysfunction and
      impairment of Ca2+ homeostasis.

PMID- 10940458
TI  - Independent component-cross correlation-sequential epoch (ICS) analysis of high
      field fMRI time series: direct visualization of dual representation of the
      primary motor cortex in human.
AB  - A new technique for functional magnetic resonance imaging (fMRI) time series
      analysis is presented. The technique referred to here as independent component
      cross correlation-sequential epoch (ICS) analysis is a hybrid technique of two
      standard methodologies of biological signal analysis, namely, data driven
      methods, represented by independent component analysis, and hypothesis driven
      methods, represented by a general linear model. The technique successfully
      identified four functionally discrete areas within the primary sensorimotor
      cortex (SMI) in normal human subjects based on blood oxygenation level dependent
      (BOLD) contrast functional magnetic resonance imaging (fMRI) time series
      performed on a high field (3.0 T) system. Each of the four areas identified
      corresponded to the four physiological subdivisions of SMI, recognized in
      primates to be essential for voluntary hand motion, namely, 4 anterior (MI-4a)
      and 4 posterior (MI-4p) of the primary motor cortex, and 3a and the 'classical'
      (Brodmann areas 1, 2, and 3b) primary sensory cortex, respectively. ICS analysis
      appears to be a highly reliable and versatile technique for fMRI time series
      analysis.

PMID- 10940460
TI  - Targets as a tool in health policy. Part II: Guidelines for application.
AB  - The use of health targets as a tool in health policy is receiving more attention.
      Beyond political will and daring, there awaits the challenge of the fruitful use
      of health targets. This means an adequate response to the complexity of
      population health in a target structure that is transparent, controllable, and
      adaptable in changing circumstances. In this article, we will review the health
      policy development cycle in relation to health target setting. First, there
      should be understanding of the problem, and a clear picture of the health status
      of the population. Then a solution can be chosen. This part is not restricted to
      the technical side of the solution, i.e. the target setting and action planning.
      It also has a political side in which responsibility is taken for the choices
      made. In the next step, the chosen solutions are implemented by government and
      stakeholders. This will be followed by a monitoring and evaluation phase, which
      will in turn provide us with an insight into the health status of the population.
      At every stage of the health policy cycle, questions which should be addressed
      when using health targets in health policy will be discussed.

PMID- 10940459
TI  - Targets as a tool in health policy. Part I: Lessons learned.
AB  - This article reviews the start of the use of targets as a tool in health policy,
      summarises the fruitful uses and frequently-heard objections, and proposes some
      conditions for successful health target setting. Targets as tool in health policy
      are based on the 'management by objectives' approach (1954). The use in health
      policy was possible due to advances in the use of epidemiology for public health
      purposes. It provisionally ends with the new health targets adopted by WHO in
      1998. The setting and monitoring of health targets is one way in which a
      government can provide leadership, guidance and strategic direction for the
      health sector. These benefits, and others, will also be reviewed. Drawbacks -
      such as political accountability and the limited malleability of society - will
      also be discussed. To overcome most of the objections, the article ends with some
      SMART conditions for successful health target setting: specific, measurable,
      achievable, realistic and time-bound. When SMART conditions are met, political
      will and daring are the recipe for a successful health target approach.

PMID- 10940461
TI  - Service quality in public and private hospitals in urban Bangladesh: a
      comparative study.
AB  - This study compared the quality of services provided by private and public
      hospitals in urban Bangladesh. Using twenty-four scale items, patient perceptions
      were sought on five aspects of service quality including responsiveness,
      assurance, communication, discipline and baksheesh. Because private hospitals are
      not subsidized, it was felt that the incentive structure would induce them to
      provide better services than public hospitals on the measures of service quality.
      This contention was largely supported. The results also indicated that both
      groups have room for improvement.

PMID- 10940462
TI  - Regulatory factors of medical care expenditures for older people in Japan-
      analysis based on secondary medical care areas in Hokkaido.
AB  - For the purpose of clarifying determinants of medical care expenditure for older
      people in Japan, we analyzed the data on medical care expenditure for older
      people in 21 secondary medical care areas in Hokkaido, the second largest island
      of Japan. The annual amount of medical expenditure per insured older person can
      be reduced into three components: annual number of medical care bills per insured
      older person days of hospitalization or visits per medical care bill and amount
      of medical expenditure per day and per insured older person. The 21 secondary
      medical care areas in Hokkaido showed large differences in per capita amount of
      both inpatient and outpatient medical expenditures for older people. Per capita
      inpatient medical expenditure for men and women correlated positively with the
      days of hospitalization per bill and the per capita number of inpatient medical
      care bills per year, but inversely with the per capita amount of expenditure per
      day of hospitalization. The same held true for outpatient medical expenditure for
      men, but for women outpatient medical expenditure correlated positively with all
      three components. Multiple regression analysis indicated the more powerful
      effects of medical care demand or supply on inpatient medical expenditure, on the
      other hand, not much powerful effects of every index were indicated on outpatient
      medical expenditure.

PMID- 10940463
TI  - Public spending on health care: how are different criteria related? A second
      opinion.
AB  - A natural response to difficult questions is to increase the number of objectives
      one pursues in the hope that each of them separately will be easy to satisfy.
      This note critically evaluates this strategy as employed in a recent paper in
      this journal [Musgrove, Health Policy 1999;47:207-223], especially its evaluation
      of the role of cost-effectiveness in priority setting in the health sector. It is
      suggested that cost-effectiveness measures provide information of limited use,
      and that the tools of applied welfare economics are sufficient to guide the
      policy choices addressed in the paper. Students of health economics and health
      policy makers would do well to be exposed to these tools.

PMID- 10940464
TI  - Lipid transfer proteins are encoded by a small multigene family in Arabidopsis
      thaliana.
AB  - Lipid transfer proteins (LTPs) are small, basic and abundant proteins in higher
      plants. They are capable of binding fatty acids and of transferring phospholipids
      between membranes in vitro. LTPs from this family contain a signal peptide and
      are secreted in the cell wall. Their biological function is presently unknown.
      LTPs have been suggested to participate to cutin assembly and to the defense of
      the plants against pathogens. A genetic approach should prove useful to provide
      clues on their in vivo functions. Here, the characterization of the LTP gene
      family in Arabidopsis thaliana is described. At least 15 genes were identified,
      their map position determined and the expression pattern characterized for six of
      them. All the sequences exhibit the typical features of plant LTPs. The molecular
      weight is close to 9 kDa, the isoelectric point is near 9 (except for three
      acidic LTPs), and typical amino acid residues such as cysteines are conserved.
      Genomic DNA blotting hybridization experiments performed using ltp1 to ltp6 as
      probes indicate that ltps form distinct 1-3 gene subfamilies which do not cross
      hybridize. Expression studies indicate that all the genes tested are expressed in
      flowers and siliques, but not in roots. Ltp1, ltp5 and ltp2 are expressed
      significantly in leaves, while ltp6 is detected only in 2-4-week-old leaves. In
      addition, ltp4 and ltp3 are strongly upregulated by abscisic acid (ABA). Tandem
      repeats can be noted concerning ltp1 and ltp2 on chromosome 2, ltp3 and ltp4 on
      chromosome 5 and ltp5 and ltp12 on chromosome 3. While ltp7, ltp8 and ltp9 map at
      the same position on chromosome 2, the other genes are dispersed throughout the
      genome. The characterization of the Arabidopsis ltp gene family will permit to
      initiate a genetic approach for determining the in vivo function(s) of these
      proteins.

PMID- 10940465
TI  - Field evaluation of seed production, shattering, and dormancy in hybrid
      populations of transgenic rice (Oryza sativa) and the weed, red rice (Oryza
      sativa).
AB  - The genetic and agronomic consequences of transferring glufosinate (Liberty)
      herbicide resistance from transgenic rice (Oryza sativa L.) lines to the noxious
      weed red rice (Oryza sativa L.) were evaluated under field conditions. Replicated
      field trials in Louisiana (LA) and Arkansas (AR) were conducted in 1997 to
      evaluate ten vegetative and reproductive traits of eight F(2) populations
      produced from controlled crosses of two transgenic, glufosinate-resistant rice
      lines and four red rice biotypes. Plant vigor and plant density at both locations
      were similar among populations derived from either transgenic or non-transgenic
      parents. Significant differences in plant height and maturity were observed among
      LA populations produced from transgenic lines when compared to corresponding
      populations developed from non-transgenic material. However, values for these
      traits were not greater than those detected in the red rice biotypes. Seed
      dormancy and seed production were not significantly different at either location
      among transgenic and non-transgenic populations. Dominant Mendelian segregation
      of glufosinate resistance was detected in 40% of the populations evaluated.
      Results of this study indicated that those populations segregating for
      glufosinate resistance responded in a location-specific manner with respect to
      life history and fecundity traits.

PMID- 10940466
TI  - Cloning and in vitro expression of the cDNA encoding a putative nucleoside
      transporter from Arabidopsis thaliana.
AB  - Nucleoside transporters are integral membrane proteins involved in the uptake or
      release of nucleosides. Their function constitutes an essential step of the
      salvage pathway of nucleotide synthesis. In order to study the function of these
      proteins in higher plants, we cloned the cDNA corresponding to the AtENT1 gene
      that encodes a putative nucleoside transporter in Arabidopsis thaliana by RT-PCR.
      The amino acid sequence of the AtENT1 protein deduced from the cloned cDNA shared
      similarity to those of eukaryotic equilibrative nucleoside transporters.
      Structure prediction indicated that the deduced AtENT1 protein might possess
      eleven putative transmembrane domains. Southern hybridization revealed that
      AtENT1 had one homologue in the Arabidopsis genome. Northern blot analysis showed
      that AtENT1 might be constitutively expressed in most Arabidopsis organs and in
      plants at different developmental stages. Two AtENT1 fusion genes, AtENT1-His-tag
      and GFP-AtENT1-His-tag, were expressed in insect cells. Confocal microscopy
      demonstrated that the GFP-AtENT1-His-tag fusion protein was targeted specifically
      to the plasma membrane of insect cells.

PMID- 10940467
TI  - Lytic activity in pearl millet: its role in downy mildew disease resistance.
AB  - Sclerospora graminicola causes downy mildew disease in susceptible pearl millet.
      Molecular basis of downy mildew disease resistance has been studied. Coleoptile
      region has been shown earlier to be the most susceptible site for attack by the
      pathogen. Lytic activity is differentially expressed in the coleoptile region of
      3-day-old pearl millet seedlings of resistant and susceptible cultivars.
      Significantly higher levels of lytic factors were measured in the coleoptile
      region of resistant cultivars (100%) than in that of susceptible cultivars (20%).
      Both constitutive and inducible lytic factors were observed in different
      resistant cultivars, and they were able to lyse the pathogen. The level of lytic
      activity correlated well with the degree of resistance as evaluated by field
      screening studies. The present study, therefore, proposes that lytic factors
      found in the coleoptile region of the pearl millet seedling, are responsible for
      the lysis of the pathogen in the resistant plant, and may therefore provide
      resistance to downy mildew disease. This study also provides a simple method to
      evaluate downy mildew resistance in pearl millet cultivars.

PMID- 10940468
TI  - Expression of threonine synthase from Solanum tuberosum L. is not metabolically
      regulated by photosynthesis-related signals or by nitrogenous compounds.
AB  - Although the control of carbon fixation and nitrogen assimilation has been
      studied in detail, little is known about the regulation of carbon and nitrogen
      flow into amino acids. In this paper the isolation of a cDNA encoding threonine
      synthase is reported (TS; EC 4.2.99.2) from a leaf lambda ZAP II-library of
      Solanum tuberosum L. and the transcriptional regulation of the respective gene
      expression in response to metabolic changes. The pattern of expression of TS by
      feeding experiments of detached petioles revealed that TS expression is regulated
      neither by photosynthesis-related metabolites nor by nitrogenous compounds. The
      present study suggests that the regulation of the conversion of aspartate to
      threonine is not controlled at the transcript level of TS. The nucleotide and
      deduced amino acid sequences of potato TS show homology to other known sequences
      from Arabidopsis thaliana and microorganisms. TS is present as a low copy gene in
      the genome of potato as demonstrated in Southern blot analysis. When cloned into
      a bacterial expression vector, the cDNA did functionally complement the
      Escherichia coli mutant strain Gif41. TS transcript was found in all tissues of
      potato and was most abundant in flowers and source leaves.

PMID- 10940469
TI  - Perturbation in linker histone content has no effect on the cell cycle but
      affects the cell size of suspension grown tobacco BY-2 cells.
AB  - Histone H1, a key structural element of eukaryotic chromosomes can be perturbed
      in plants in vivo by overexpression or by a change in the proportion of native H1
      variants (Prymakowska-Bosak M., Przewloka M., Iwkiewicz J., Egierszdorff S.,
      Kuras M., Chaubert N., Gigot C., Spiker S., Jerzmanowski A., Histone H1
      overexpressed to high level in tobacco affects certain developmental programs but
      has limited effect on basal cellular functions, Proc. Natl. Acad. Sci. U.S.A. 93
      (1996) 10250-10255; Prymakowska-Bosak M., Slusarczyk J., Przewloka M., Kuras M.,
      Lichota J., Kilianczyk B., Jerzmanowski A., Linker Histones Play a Role in Male
      Meiosis and the Development of Pollen Grains in Tobacco, Plant Cell 11 (1999)
      2317-2330). In order to analyze the possible causes of the specific phenotypic
      changes observed in whole plants we employed a simpler system of tobacco BY-2
      cell line. We show that the BY-2 cells engineered to overexpress a major variant
      of Arabidopsis H1 or with the level of native major variants of H1 decreased by
      antisense strategy maintain the normal ability to grow and the normal length of
      the cell cycle. In the cells with perturbed H1 histones no change was observed in
      the organization of mitotic spindle or actin filaments of the cytoskeleton. The
      only visible phenotypic change occurred in cells overexpressing H1 that showed an
      increased frequency of cells with unusually large size. This phenotype was
      correlated with subtle but reproducible changes in the organization of cortical
      microtubules.

PMID- 10940470
TI  - Characterization of MZm3-3, a Zea mays tapetum-specific transcript.
AB  - A cDNA, MZm3-3, was isolated by differential screening of a cDNA library from Zea
      mays meiotic stage anthers against cDNA of 3-week-old seedlings. Characterization
      of this cDNA indicated that the MZm3-3 gene is expressed specifically during male
      gametogenesis. Its expression is highly and preferentially detected in the
      tapetum, from the pollen mother cell to uninucleated microspore stages. It
      encodes a short alkaline protein of 10.6 kDa, with a conserved pattern of eight
      cysteine residues. Sequence analysis showed that these features are shared with
      lipid transfer proteins and some male-flower-specific proteins. The presence of a
      putative signal peptide indicates that MZm3-3 enters into the secretory pathway
      to then be released into the anther loculus. Based on these features, the
      secretory activity of the tapetum and the temporal expression pattern of MZm3-3,
      a contribution to pollen coat formation is suggested. Southern blot analyses
      demonstrated the presence of closely related genes, indicating that MZm3-3
      belongs to a multigene family.

PMID- 10940471
TI  - Molecular cloning and expression of cDNAs encoding alcohol dehydrogenases from
      Vitis vinifera L. during berry development.
AB  - Three full-length cDNAs (VvAdh1, VvAdh2, and VvAdh3) encoding alcohol
      dehydrogenases (EC 1.1.1.1) were obtained from grape berries (Vitis vinifera L.)
      by means of PCR and RACE. Pairwise comparisons at the nucleotide level showed
      that the three cDNAs displayed strong homology in the coding region, but were
      highly divergent in the 5' and 3' untranslated regions. VvAdh1 and VvAdh2
      corresponded to the two previously characterised Adh genes from grapevine, but
      VvAdh3 was unrelated to known grapevine Adh sequences. The two first cDNAs
      presented a single ORF of 380 amino acids, whereas the last one has two
      additional residues. Moreover, the three encoded polypeptides possessed the 22
      residues strictly conserved between Adh from different kingdoms. Expression
      pattern of the individual isogenes was investigated during fruit development.
      Specific primers were designed, and quantitative RT-PCR experiments were
      performed to increase the sensitivity of detecting isogenes with a low expression
      level. Results presented here revealed different developmental regulation of the
      three Adh isogenes during fruit ripening. VvAdh1 and VvAdh3 transcripts were
      temporarily accumulated in young, developing berry, whereas VvAdh2 was
      overexpressed later in fruit development, from the onset of ripening (veraison).
      Expression analysis also indicated that VvAdh2 accounted for most of the Adh
      mRNAs present in berries during development. The increased ADH activity detected
      in berries correlated with the expression pattern of VvAdh2 transcripts. The
      VvAdh2 and VvAdh3 encoded enzymes were purified from overexpressing E. coli
      cells. Comparison of kinetic properties of the two ADH enzymes showed a
      difference in affinity with either ethanol or acetaldehyde as substrates.
      Significance of multiple Adh expressed in berries is discussed.

PMID- 10940472
TI  - Ammonium, bicarbonate and calcium effects on tomato plants grown under saline
      conditions.
AB  - Tomato plants (70 days old) were grown in hydroponic culture into a greenhouse,
      where supply of inorganic carbon, ammonium and calcium to saline nutrient
      solution, was investigated in order to reduce the negative effect of salinity.
      After 70 days, an ameliorating effect upon the decrease in growth observed under
      salinity was only observed with the treatments NaCl+Ca(2+) and NaCl+HCO(3)(
      )+NH(4)(+)+Ca(2+). A large reduction of hydraulic conductance (L(0)) and stomatal
      conductance (G(s)) was observed with all treatments, compared with the control.
      However, the reductions were less when NaCl and Ca(2+) were added together.
      Organic acids (mainly malic acid) in the xylem were decreased with all treatments
      except with NaCl+NH(4)(+) and with all single treatments added together
      (NaCl+HCO(3)(-)+NH(4)(+)+Ca(2+)). Amino acid concentrations in the xylem (mainly
      asparagine and glutamine) decreased when plants were treated with NaCl and
      NaCl+Ca(2+), but there was a large increase in the plants treated with
      NaCl+NH(4)(+) or with all treatments together. As HCO(3)(-) is an important
      source of carbon for NH(4)(+) assimilation, the increase in the concentration of
      amino acids and organic acids caused by the treatments that contained NH(4)(+),
      support the idea that fixation of dissolved inorganic carbon was occurring and
      that the products were transported via the xylem to the shoot. The ameliorating
      effect of Ca(2+) on root hydraulic conductivity plus the increase of NH(4)(+)
      incorporation into the amino acid synthesis pathway possibly due to dissolved
      inorganic carbon fixation, could reduce the negative effect of salinity on tomato
      plants.

PMID- 10940473
TI  - Distribution of microsatellites in relation to coding sequences within the
      Arabidopsis thaliana genome.
AB  - The distribution of repetitive sequences, or microsatellites, formed by either
      one or two base pairs and longer than eight units, has been studied in almost 1
      Mb of the sequenced Arabidopsis thaliana genome. Except for those formed by only
      G and C residues, the repetitions are more abundant in the Arabidopsis genome
      than can be calculated from its nucleotide composition. They are distributed in
      proportions higher than expected in introns, and in the intergenic regions both
      proximal and distal to the coding sequences. In exons, only the TC/GA
      microsatellite seems to be particularly abundant. The AT/TA microsatellites
      produce more length variation between Arabidopsis ecotypes than the A/T repeated
      sequences. These two classes are more abundant per kilobase than coding sequences
      in the Arabidopsis genome. The results indicate not only that the presence of
      microsatellites is not an effect of random distribution of nucleotides, but that
      their resolution as molecular markers may be equivalent to the number of genes
      and also that they do not seem to be systematically linked to specific regulatory
      sequences proximal to genes.

PMID- 10940474
TI  - Purification and characterization of UDP-glucose: hydroxycoumarin 7-O
      glucosyltransferase, with broad substrate specificity from tobacco cultured
      cells.
AB  - The enzyme UDP-glucose: hydroxycoumarin 7-O-glucosyltransferase (CGTase), which
      catalyzes the formation of scopolin from scopoletin, was purified approximately
      1200-fold from a culture of 2,4-D-treated tobacco cells (Nicotiana tabacum L. cv.
      Bright Yellow T-13) with a yield of 7%. Purification to apparent homogeneity, as
      judged by SDS-PAGE, was achieved by sequential anion-exchange chromatography,
      hydroxyapatite chromatography, gel filtration, a second round of anion-exchange
      chromatography, and affinity chromatography on UDP-glucuronic acid agarose. The
      purified enzyme had a pH optimum of 7.5, an isoelectric point (pI) of 5.0, and a
      molecular mass of 49 kDa. The enzyme did not require metal cofactors for
      activity. Its activity was inhibited by Zn(2+), Co(2+) and Cu(2+) ions, as well
      as by SH-blocking reagents. The K(m) values for UDP-glucose, scopoletin and
      esculetin were 43, 150 and 25 uM, respectively. A study of the initial rate of
      the reaction suggested that the reaction proceeded via a sequential mechanism.
      The purified enzyme preferred hydroxycoumarins as substrates but also exhibited
      significant activity with flavonoids. A database search using the amino terminus
      amino acid sequence of CGTase revealed strong homology to the amino acid
      sequences of other glucosyltransferases in plants.

PMID- 10940475
TI  - Antioxidative parameters in the seedlings of pigeonpea (Cajanus cajan (L.)
      Millspaugh) in response to Zn and Ni stresses.
AB  - The zinc (Zn) and nickel (Ni) as oxidative stress factors and associated
      responses of 6-day-old seedlings of two pigeonpea (Cajanus cajan (L.) Millspaugh)
      cultivars namely LRG30 and ICPL87 were studied. Zinc and Ni exposure increased
      lipid peroxidation in relation to their concentration. Reduction in dry matter
      accumulation of roots and shoots was noticed in Zn and Ni treatments. The
      activities of antioxidative enzymes such as superoxide dismutase, peroxidase and
      glutathione reductase registered higher values and the activity of catalase and
      the antioxidative substances such as ascorbic acid and total glutathione contents
      registered lower values in all the Zn and Ni treatments when compared to their
      controls. The levels of catalase, peroxidase and glutathione reductase and
      ascorbic acid and total glutathione contents were high in cv. LRG30 than in cv.
      ICPL87 in response to Zn and Ni treatments. However, the activity of superoxide
      dismutase, the major scavenger of O(2)(&z.rad;-) radical registered higher values
      in cv. ICPL87. The cv. LRG30 is less sensitive to Zn and Ni treatments compared
      to the cv. ICPL87. Correlation coefficients between the different antioxidant
      parameters and metal dose level, or dry matter accumulation, were established,
      assessing for an induced-oxidative stress. Additional evidence was provided by
      comparing the sensitivity of the two cultivars.

PMID- 10940476
TI  - Zygotic and somatic embryos of cucumber (Cucumis sativus L.) substantially differ
      in their levels of abscisic acid.
AB  - In this work we studied the changes in the level of abscisic acid (ABA) in the
      somatic embryos (SE) and in the diploid and triploid zygotic embryos (ZE) of the
      same cucumber line during embryogenesis and seed maturation. Different stages of
      seed development were selected according to days after pollination (DAP): 21, 24,
      28, 35, 42 and 42 plus 14 days of storage for diploid ZE and 35 and 42 plus 14
      days of storage for triploid ZE. SE were collected at five growth stages from
      globular to late cotyledonary. Quantitative analysis of ABA was performed using
      an enzyme linked immunosorbent assay (ELISA) test. Both types of embryos -
      somatic and zygotic - essentially differed in their levels of ABA, always being
      the highest for 2n ZE and lowest for SE. Although the concentration of ABA in ZE
      of the triploid line was higher when compared with the same DAP, when the
      comparison was based on embryo development, both the concentration and content of
      ABA was higher in the diploid line. The pattern of developmental changes in the
      level of ABA in the diploid ZE was consistent with that known for other species.
      An increase was observed during embryo development with a peak (51.1 ug g(-1) FW
      or 0.95 ug per embryo) at the final stage of embryo formation between 21 and 24
      DAP. A sharp decrease in the ABA level then took place (more than 3-fold within 4
      days) and was followed by a further reduction as the seed matured. The maximal
      and minimal values for ABA concentration differed about 35-fold. SE differed
      substantially from their zygotic counterparts not only in that the concentration
      of ABA was extremely low (0.005-0.011 ug g(-1) FW) but also that no significant
      changes occurred during embryo development and no peak of ABA concentration was
      observed. Other tissues of the ovule and ovary also contained ABA and could be a
      source of ABA for the embryo.

PMID- 10940477
TI  - Retinoic acid receptor fusion proteins: friend or foe.
AB  - Acute promyelocytic leukemia (APL) is characterized by a block in differentiation
      of hematopoietic cells at the promyelocytic stage of development. This disease is
      uniquely sensitive to treatment with pharmacological doses of all-trans retinoic
      acid (ATRA), and the combination of ATRA with chemotherapy has improved the
      durable disease-free survival in these patients to up to 80%. APL is
      characterized by chromosomal translocations that lead to the fusion of the
      retinoic acid receptor-alpha (RARalpha) to various partner genes. RARalpha
      functions as a ligand-inducible transcription factor and the aberrant RARalpha
      fusion proteins contribute to leukemic transformation by dominant inhibition of
      the expression of target genes that are important for cellular differentiation.
      This may at least in part be explained by an abnormally strong interaction with
      corepressor proteins leading to deacetylation of DNA and silencing of target
      genes. Most RARalpha fusion proteins can still be induced to transactivate genes,
      but only at very high doses of ligand, explaining why pharmacological doses of
      ATRA are necessary to obtain a therapeutic effect in these patients.

PMID- 10940478
TI  - Glucocorticoids inhibit the transcriptional response of the uncoupling protein-1
      gene to adrenergic stimulation in a brown adipose cell line.
AB  - Glucocorticoids may inhibit brown adipose tissue (BAT) thermogenesis acting at a
      central level as well as reducing the responses of the tissue to adrenergic
      stimulation in vivo. This latter effect is not well understood. We investigated
      whether or not glucocorticoids directly reduce the expression of the key molecule
      for BAT thermogenesis, uncoupling protein-1 (UCP1), and if so, to what extent and
      by what mechanisms. We used HIB-1B brown adipose cells obtained from a hibernoma.
      The response of UCP1 mRNA to adrenergic stimulation in these cells is
      qualitatively and quantitatively similar to that seen in vivo. Dexamethasone and
      other glucocorticoids, given simultaneously with NE, nearly abolish the ensuing
      UCP1 mRNA accumulation. This effect was negated by the glucocorticoid receptor
      antagonist RU-486. Significant inhibition is seen within the physiological range
      of concentrations, with ID(50)s for dexamethasone and corticosterone of 1 and 75
      nM, respectively. Within the time span of the experiments, glucocorticoids did
      not reduce the strength of the NE signal nor did they necessitate ongoing protein
      synthesis or reduce the stability of mature UCP1 mRNA, but they significantly
      inhibited the stimulation of transcription by NE in a run-on in vitro
      transcription assay. These observations indicate that glucocorticoids are
      powerful inhibitors of the UCP1 gene response to adrenergic stimulation acting at
      transcriptional level, and provide further evidence for a global inhibitory
      effect of glucocorticoids on BAT thermogenesis.

PMID- 10940479
TI  - Role of Ets2 in cyclic AMP regulation of the human chorionic gonadotropin beta
      promoter.
AB  - Activation of the human chorionic gonadotropin beta (hCGbeta) by the protein
      kinase A (PKA) pathway has been shown to occur through an activating protein-2
      (AP-2)-dependent mechanism. However, in HepG2 cells, which are deficient in AP-2,
      the PKA catalytic subunit is still able to stimulate the hCGbeta promoter. Ets2
      plays a critical role in placental development as revealed by placental
      abnormalities in Ets2 knockout mice. Transfection of Ets2 into JEG-3 placental
      cells causes a slight, but reproducible, increase in hCGbeta promoter basal
      activity. However, cotransfection with the PKA catalytic subunit causes a strong
      synergistic increase in hCGbeta promoter activity. Ets2 synergistic activation of
      the hCGbeta promoter is specific for the PKA pathway, as activation of the ras
      pathway, which also acts through Ets2, does not activate the hCGbeta promoter. c
      Jun-mediated repression of hCGbeta is inhibited by Ets2 cotransfection,
      indicating that protein-protein interactions may be responsible for Ets2
      activation of the hCGbeta promoter.

PMID- 10940480
TI  - Expression of adrenocortical steroidogenic acute regulatory (StAR) protein is
      influenced by chromaffin cells.
AB  - Cell-cell interactions are crucial role for the proper functioning of endocrine
      glands. We recently demonstrated that interactions of chromaffin and cortical
      cells are important for adrenocortical steroidogenesis. However, the molecular
      mechanisms have not been elucidated and it is unclear if this involves acute
      and/or chronic processes. By Northern analysis and the quantitative technique of
      TaqMan PCR we investigated whether chromaffin cells influence the regulation of
      StAR and the peripheral benzodiazepine receptor (PBR), both required for the rate
      limiting step, the delivery of cholesterol to the inner mitochondrial membrane.
      StAR mRNA levels in bovine adrenocortical cells were increased by incubation with
      chromaffin cell-conditioned medium (CCM). Short-term treatment for 4 h resulted
      in a greater stimulation (229+/-29% of basal, mean+/-SEM) than did longer
      incubation times of 8 h and 5 days (159+/-13 and 177+/-24%). Neither short nor a
      long-term treatment affected PBR expression. Consistently, the major secretion of
      chromaffin cells, epinephrine dose-dependently stimulated StAR expression with no
      effect on PBR mRNA. In conclusion, adrenomedullary secretory products are not
      necessary for the maintenance of PBR expression but facilitate steroid
      biosynthesis by increasing StAR mRNA expression and therefore can account for an
      ACTH-independent regulation of the rate-limiting step in steroidogenesis.

PMID- 10940481
TI  - TRH regulates Kv1.5 gene expression through a Galphaq-mediated PLC-independent
      pathway.
AB  - Thyrotropin-releasing hormone (TRH) decreases transcription of the Kv1.5 K(+)
      channel gene in GH(3) pituitary cells. Here, we examine whether TRH utilizes Gq
      activated phospholipase C, Gs or Gi to produce this response. We report that
      expression of constitutively active Galphaq mimicked and occluded the TRH effect.
      In contrast, expression of activated Galpha(S) or Galpha(i2) had no effect on
      Kv1. 5 mRNA expression. Furthermore, pertussis and cholera toxins failed to block
      the TRH-induced decrease in channel mRNA. Surprisingly, despite the role of Gq,
      the phospholipase C inhibitor U73122 did not alter down-regulation of channel
      mRNA by TRH, although it abolished the TRH-induced increase in intracellular
      [Ca(2+)] and up-regulation of c-fos mRNA. Furthermore, depletion of an
      intracellular Ca(2+) pool or inhibition of protein kinase C did not block the TRH
      induced decrease in Kv1.5 mRNA. These results indicate that TRH-induced down
      regulation of Kv1.5 gene expression is mediated by Galphaq proteins, but does not
      require PLC activation.

PMID- 10940482
TI  - Transcription factor expression and hormone production in pancreatic AR42J cells.
AB  - AR42J is an exocrine pancreatic cell line that has been reported to differentiate
      towards an endocrine phenotype when stimulated with various growth factors, such
      as activin A, hepatocyte growth factor (HGF), betacellulin or glucagon-like
      peptide 1. In our experiments, AR42J-B13 cells differentiated morphologically in
      response to the growth factor treatment as reported previously. However, they
      failed to express the insulin gene. We found that the cells did not express
      several transcription factors known to be found in the beta-cell, including
      Nkx6.1, isl-1, Pax4 and Pax6. In addition, the mRNA level for pdx-1 and Nkx2.2
      were very low in comparison to the insulinoma cell lines INS-1 and RINm5F.
      However, some transcription factors typically found in beta-cells and
      neuroendocrine cells were expressed also in the AR42J-B13 cells. These included
      BETA2/NeuroD, HNF1alpha, C/EBPbeta and IA-1. Unlike the insulinoma cells, AR42J
      cells expressed the exocrine transcription factor p48. In order to induce
      endocrine differentiation, we transfected the AR42J-B13 cells with the full
      length cDNAs of isl-1, Nkx6.1, Nkx2.2 and pdx-1 under the control of the CMV
      promoter, both separately and in combinations. The expression of Nkx2.2 led
      consistently to the appearance of pancreatic polypeptide but not insulin,
      glucagon or somatostatin mRNA. The PP mRNA expression in Nkx2.2 cDNA transfected
      cells was independent of the growth factor treatment used for differentiating
      AR42J cells. In conclusion, the AR42J-B13 line possesses some features of a
      pancreatic neuroendocrine cell. However, we were unable to confirm the capacity
      of these cells to differentiate into insulin-producing cells. Our results
      indicate that Nkx2.2 plays a role in the transcriptional regulation of PP
      expression.

PMID- 10940483
TI  - Prolactin and polyamine catabolism: specific effect on polyamine oxidase activity
      in rat thymus.
AB  - Much evidence suggests that prolactin has an immunoregulatory function and that
      its effects on cells of the immune system depend on the level and specific forms
      of the receptors present on the target cells. The effect of administration of
      prolactin on polyamine catabolism was investigated in thymus of male intact rats
      by measuring the activities of spermidine/spermine N(1)-acetyltransferase and
      polyamine oxidase, because of the relationships between polyamines (especially
      putrescine) and the immune system. The administration of prolactin to rats
      resulted in the rapid induction of spermidine/spermine N(1)-acetyltransferase
      activity in the thymus (1.6-times the level of control rats, within 4 h), and in
      a marked decrease in polyamine oxidase activity at 24 h. The changes in enzyme
      activities were accompanied by an increase in putrescine concentration and a
      decrease in spermidine and spermine concentrations. In the spleen, prolactin
      increased SAT activity only 24 h after administration and was ineffective on PAO
      activity.

PMID- 10940484
TI  - Triac regulation of transcription is T(3) receptor isoform- and response element
      specific.
AB  - 3,5,3'-triiodothyroacetic acid (Triac) is a naturally occurring triiodothyronine
      (T(3)) analog, which has been used on an empirical basis to treat the syndrome of
      resistance to thyroid hormone (RTH). The aim of our studies was to compare the
      effects of Triac and T(3) on negative and positive thyroid hormone response
      elements (TREs). We used transient transfections with luciferase reporter genes
      to show that on palindromic, inverted palindrome and human TRH reporters, Triac
      is more potent than T(3) for transcriptional regulation by TRbeta1 and TRbeta2
      isoforms, while regulation by TRalpha1 is equivalent for both ligands. Other TREs
      (direct repeat, hTSHalpha and hTSHbeta) are not regulated differently by Triac
      and T(3). Dose-response curves show that the difference between Triac and T(3) is
      maximal in the 1-10 nM range. Receptor-binding studies reveal a greater affinity
      of Triac than T(3) for TRbeta1 and TRbeta2 isoforms, which could explain its
      isoform-specific effects. These data suggest that the TRE- and TR isoform
      specific effects of Triac favor its use in RTH.

PMID- 10940485
TI  - Bromocriptine restores angiotensin II response in pituitary hyperplasia.
AB  - In estrogen-induced pituitary hyperplasia AII-evoked prolactin release is
      decreased and the octapeptide does not generate a spike elevation in [Ca(2+)](i)
      in vitro. We studied whether or not bromocriptine could restore AII response in
      diethylstilbestrol treated rats. Co-administration of bromocriptine resulted in
      involution of pituitary size and lowering of serum prolactin. In vitro, prolactin
      release per cell was reduced in the hyperplastic group, and levels were not
      significantly increased by in vivo bromocriptine treatment. Immunocytochemical
      analysis revealed that hyperplastic pituitaries contained fewer prolactin
      granules than control pituitaries, and that bromocriptine, did not increase
      prolactin storage. Nevertheless, in this group, prolactin response to AII
      increased, and AII evoked a consistent spike in [Ca(2+)](i), albeit lower than in
      the control group. Such spike was abolished by thapsigargin, and not by removal
      of extracellular calcium or by K(+), indicating that it was mainly dependent on
      intracellular calcium stores, as in normal cells. We conclude that bromocriptine
      treatment partially restores AII response in the hyperplastic pituitary.

PMID- 10940486
TI  - Apoptosis and apoptosis-related proteins in human endometrium.
AB  - Apoptosis has been shown to be an important regulator of endometrium function. To
      study the regulation of apoptosis in the endometrium during the normal menstrual
      cycle, the expression of the apoptosis related proteins Bcl-2 and Bax and their
      correlation to serum estradiol and progesterone, as well as to a replication
      related antigen Ki-67 were analyzed. Nine uterine tissue samples and thirty-nine
      endometrial biopsy specimens were studied. Apoptosis was studied quantitatively
      by Southern blot analysis of internucleosomal cleavage of genomic DNA, and
      qualitatively by using in situ 3'-end labeling of fragmented DNA, and Bcl-2, Bax
      and Ki-67 were detected and quantified immunohistochemically. Apoptotic cells
      were mostly detected in the glandular epithelium of late secretory and
      menstruating endometrium. Immunostaining of Ki-67 was detected predominantly in
      proliferative endometrium. The expression of Bcl-2 was high in proliferative
      endometrium and decreased in the secretory phase, being very low or absent in the
      mid- and late secretory and menstruatory phases. Similarly, Bax expression also
      decreased, but was still present throughout the secretory phase. In human
      endometrium, apoptosis occurs predominantly in the late secretory and menstrual
      phases, and is related to alterations in the expression of Bcl-2 and Bax. A
      decrease in the Bcl-2/Bax ratio in the early secretory phase precedes DNA
      fragmentation and may predispose the cells to apoptosis.

PMID- 10940487
TI  - A putative white adipose tissue specific nuclear orphan receptor that interacts
      with the cAMP-response element of the human beta3-adrenergic receptor gene.
AB  - The authors previously reported that one of the cAMP-response elements (CREs) of
      the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is
      distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue
      specific factor-1) since it is preferentially expressed in WAT. In this work, we
      have shown the absence of DNA binding or transcriptional activity of this factor
      in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to
      constitute an octameric element that is highly homologous to the binding site for
      some members of the nuclear hormone receptor superfamily. Using the response
      elements of other adipocyte-specific nuclear receptors as competitors, a 'cross
      talk' between WATSF-1 and these response elements has been demonstrated. However,
      the affinity of WATSF-1 for these response elements differs from that for
      beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific
      nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to
      be enhanced by phosphatase treatment, suggesting that phosphorylation may play an
      important role in the functional modulation of this factor. In an effort to prove
      that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular
      model of WAT, that can undergo differentiation into adipocytes. The DNA binding
      and transcriptional activity of this factor appeared during differentiation of
      the cells. Taken together, these results demonstrate that WATSF-1 is a putative
      white adipocyte-specific nuclear orphan receptor induced during adipogenesis and
      is a transcriptional activator through one of the CREs of the human beta3-AR
      gene. Targeting this factor may be a novel therapeutic approach to stimulation of
      the beta3-AR signal transduction pathway in adipose tissues.

PMID- 10940488
TI  - The regulation of leptin gene expression in the C6 glioblastoma cell line.
AB  - The hormone leptin is implicated in the regulation of appetite and body weight in
      rodents, primates and humans. We reported that the leptin gene (ob) is expressed
      in the brain, but the factors which control ob expression in the central nervous
      system are not known. We previously showed that brain-derived rat C6 glioblastoma
      cells express ob mRNA and protein. In the present study we examined the
      regulation of ob expression in C6 cells. Leptin and leptin receptor
      immunoreactivity was detected in C6 cells, suggesting a possible autocrine role
      for leptin. The identity of the leptin immunoreactivity (OB-ir) in C6 cells was
      confirmed by immunoprecipitation and Western blotting using two leptin specific
      polyclonal antibodies. Using RT-PCR analysis a product of the expected size for
      the short, but not the long, leptin receptor isoform was detected in C6 cells.
      Cells were maintained in serum-free (SF) media for 0-24 h in the presence of
      various regulators of leptin expression. Leptin mRNA levels were significantly
      higher in cells treated with dbcAMP (1 mM), IGF 1 (100 ng/ml) or insulin (5
      microg/ml) compared to SF controls. In contrast, corticosterone (10(-7)M) reduced
      leptin mRNA. In the presence of dbcAMP, C6 cells undergo a dramatic alteration in
      morphology which is coincident with an apparent increase in the number of leptin
      ir nuclei and an increase in leptin immunoreactivity. In contrast to C6 cells,
      glucocorticoids are reported to increase leptin levels in adipocytes/adipose
      tissue, while increases in intracellular cAMP levels are reported to reduce
      leptin levels. Overall, our in vitro data suggest that the regulation of leptin
      gene expression in C6 glioblastoma cells is different from that in adipocytes.

PMID- 10940489
TI  - DNA immunization in vivo down-regulates nuclear all-trans retinoic acid receptors
      in mouse spleen cells.
AB  - Nuclear retinoid receptors - retinoic acid inducible transcription factors -
      participate in pathways influencing many components of the immune system. In the
      present study in vivo effects of DNA-based immunization of mice on binding
      parameters of all-trans retinoic acid receptors (RARs) in spleen cell nuclei was
      investigated. A eucaryotic expression vector encoding the gene for the model
      enzyme beta-galactosidase of Escherichia coli (pCMV-beta) was used for
      intradermal injection. Furthermore, immunostimulatory CpG motifs, which stimulate
      the expression of various cytokines and may serve as a 'danger signal' for the
      mammalian immune system, were coinjected as oligodeoxynucleotides. The results
      demonstrate that the concentration of RARs was significantly reduced in the late
      phase of the primary immune response (21 days after injection of plasmid DNA
      indicated by high affinity IgG antibodies and IFN-gamma expression). Coinjection
      of CpG motifs did not change the course of the humoral response but enhanced and
      accelerated the proliferative response and expression of IFN-gamma, which
      correlated with the reduced RARs concentration.

PMID- 10940490
TI  - Involvement of Bcl-2 family proteins in germ cell apoptosis during testicular
      development in the rat and pro-survival effect of stem cell factor on germ cells
      in vitro.
AB  - A large part of germ cells die apoptotically during testicular development in
      rodents. In the present study, a wave of germ cell apoptosis was observed between
      days 10 and 30 of postnatal life by in situ 3'-end labeling and DNA fragmentation
      analysis. To explore the potential involvement of Bcl-2 family members in this
      process, the expression and localization of some Bcl-2 family proteins (Bcl-2,
      Bcl-xL, Bcl-w, Bak, Bax, and Bad) and p53 were analyzed during testicular
      development in the rat by Western blotting and immunohistochemistry. The dynamic
      changes in the expression profiles of Bcl-2 family proteins are consistent with a
      model in which germ cells are primed for apoptosis during the first cycle of
      spermatogenesis by de novo expression of the death effectors Bax and Bad in a p53
      dependent manner and these proteins are prevented from triggering further
      apoptosis after the first spermatogenic cycle has been set up by anti-apoptotic
      Bcl-2 family proteins Bcl-xL and Bcl-w. To examine whether the pro-survival
      effect of stem cell factor (SCF) on germ cells in vitro is mediated by Bcl-2
      family proteins, the correlation between the pro-survival effect of SCF on germ
      cells and the expression of the above-mentioned apoptosis-related gene products
      in the seminiferous tubules at stage XII of the epithelial cycle were also
      investigated using a tubular culture system. The data suggest that SCF supports
      germ cell survival during spermatogenesis by up-regulating pro-survival Bcl-2
      family proteins, Bcl-w and Bcl-xL, and down-regulating pro-apoptosis Bcl-2 family
      proteins, e.g. Bax.

PMID- 10940491
TI  - Tamoxifen-induced cell death in malignant melanoma cells: possible involvement of
      the insulin-like growth factor-1 (IGF-1) pathway.
AB  - Recent data indicate that the estrogen receptor (ER) blocker tamoxifen (TAM) can
      induce cell death in malignant melanoma cells. However, as shown in the present
      study and several other studies melanoma cells usually do not express classical
      ERs. In the present study we investigated whether the cytotoxic effect of TAM on
      melanoma cells could depend on interference with the expression or function of
      the insulin-like growth factor-1 receptor (IGF-1R), a plasma membrane receptor
      important for cell survival in this tumor cell type. Several melanoma cell lines
      were included in the analysis. Administration of TAM at a concentration of 15
      microm or more resulted in cell death of the melanoma cells within 48 h. TAM
      treatment was correlated to a slight to moderate inhibition of IGF-1 binding to
      IGF-1R. Since it has been reported that TAM can increase the release of IGF
      binding proteins (IGFBPs) we then investigated whether this mechanism could
      underly the decreased IGF-1 binding. However, we could demonstrate that the
      amount of released IGFBPs were unchanged or decreased in TAM-treated cells.
      Whereas TAM did not have any strong effect on IGF-1 binding and the expression of
      IGF-1R at the cell surface, it was was found to efficently block tyrosine
      phosphorylation of IGF-1R beta-subunit. Taken together, our data suggest that TAM
      induced cytotoxicity of malignant melanoma cells can be due to inactivation of
      IGF-1R.

PMID- 10940492
TI  - Novel, thapsigargin-insensitive intracellular Ca(2+) stores control growth
      hormone release from goldfish pituitary cells.
AB  - The relative contribution of intracellular Ca(2+) stores to basal and agonist
      stimulated hormone release in pituitary cells is still not well understood,
      especially in non-mammalian vertebrates. Using ratiometric Ca(2+) imaging of
      single identified goldfish somatotropes, along with time-resolved measurements of
      growth hormone (GH) secretion, we investigated the Ca(2+)-dependent signal
      transduction of two endogenous regulators of GH release from the goldfish
      pituitary. Two gonadotropin-releasing hormones (sGnRH and cGnRH-II) initiated GH
      release in nominally Ca(2+) free conditions. GnRH-evoked GH release was additive
      to KCl-stimulated GH responses. Ca(2+) signals and GH release elicited by both
      GnRHs were abolished by pretreatment with TMB-8, which blocks the release of
      Ca(2+) from intracellular stores. GnRH-stimulated GH secretion is mediated by
      caffeine-sensitive intracellular Ca(2+) stores that are functionally independent
      from those sensitive to thapsigargin and other inhibitors of SERCA-type
      Ca(2+)/ATPases. The caffeine/TMB-8-sensitive Ca(2+) stores are also involved in
      spontaneous Ca(2+) signalling and the maintenance of prolonged GH release.

PMID- 10940493
TI  - Comparison of transcriptional synergy of estrogen receptors alpha and beta from
      multiple tandem estrogen response elements.
AB  - Estrogen receptors alpha and beta (ERalpha and ERbeta) act as ligand-dependent
      transcriptional enhancers. We reported that ERalpha induces synergistic
      activation of luciferase reporter gene activity in response to E(2) from three or
      four tandem copies of a consensus estrogen response element (ERE) in transiently
      transfected MCF-7 cells. Here we addressed three questions: (1) is the
      synergistic activation of reporter gene activity from multiple tandem EREs by
      ERalpha restricted to MCF-7 cells?; (2) does ERbeta induce synergistic activation
      of reporter activity from multiple tandem EREs?; and (3) does ERbeta bind
      cooperatively to multiple tandem EREs? To address the first two questions, ER
      negative CHO-K1 cells were co-transfected with ERalpha or ERbeta and ERE-driven
      reporter plasmids. Both ERalpha and ERbeta activated ERE-driven luciferase gene
      activity in an estradiol-dependent manner. Induction by ERbeta was lower than
      ERalpha from each ERE. We demonstrate that both ERalpha and ERbeta induce
      transcriptional synergy with three or four, but not two, tandem copies of an ERE.
      Electrophoretic mobility shift assays (EMSA) indicated an increase in ER-ERE
      binding affinity associated with cooperative binding of ERalpha and ERbeta to
      multiple EREs that may be responsible for transcriptional synergy in transiently
      transfected cells. We also postulate that interaction of ERalpha and ERbeta with
      coactivators may also play a role in transcriptional synergy.

PMID- 10940494
TI  - 2-Methoxyestradiol, an endogenous estrogen metabolite, induces thyroid cell
      apoptosis.
AB  - The etiology of autoimmune thyroid diseases is unclear; however, the extreme
      female predominance suggests that sex hormones may have a pathogenic role. 2
      Methoxyestradiol (2-ME) is present in the serum of women during the ovulatory and
      luteal phases of the menstrual cycle, and during pregnancy. We investigated the
      actions of 2-ME and estrogen on thyroid follicular cells. 2-ME induced dramatic
      changes in cell morphology and decreased the viability of the cells, as well as
      disrupted the structural integrity of cultured thyroid follicles. Flow cytometric
      analysis showed that 2-ME halted cell proliferation by arresting the cells in the
      G2/M cell-cycle compartment. Prolonged exposure to 2-ME led to apoptosis and to
      increased release of the autoantigen thyroid peroxidase (TPO). 17beta-estradiol
      failed to produce a similar effect even in 40-fold molar excess to 2-ME. Co
      treatment with estrogen receptor antagonists did not alter the 2-ME effect,
      indicating that 2-ME was not operating through a classic nuclear estrogen
      receptor. In conclusion, this study indicates that 2-ME induces G2/M cycle
      arrest, apoptosis and the disruption of thyroid follicles. This process results
      in the release of thyroid antigens that may play a role in high incidence of
      thyroid autoantibodies and autoimmune thyroid disease in women.

PMID- 10940495
TI  - Effect of tamoxifen treatment on the endometrial expression of human insulin-like
      growth factors and their receptor mRNAs.
AB  - The effect of tamoxifen (Tam) treatment on the endometrial expression of IGF-I
      and II/IGF-IR and IIR mRNAs was assessed by measuring the levels of expression of
      these mRNAs in the endometrial samples of Tam-treated postmenopausal breast
      cancer patients by RT-PCR assays. The levels of these mRNAs were compared with
      those in normal endometrium and in Type I and Type II endometrial carcinomas
      (EC). The promoter-specific transcript profiles of IGF-I and II were also
      elucidated. The levels of IGF/IGF-R mRNAs in the endometrium from Tam-treated
      patients were found to be comparable with the high levels of these mRNAs observed
      in the proliferative and early secretory phase endometrium and in the samples of
      Type I EC. These results indicate that Tam acts as an estrogen agonist in
      inducing the endometrial expression of these genes. Tam stimulated transcription
      from the multiple promoters of IGF-I and II, with the exception of IGF-II P2
      promoter, in which case the transcription across exon 4 appeared to be inhibited.
      The profiles of IGF-I and II transcripts of endometrium from Tam-treated patients
      were similar to Type I EC but differed considerably from those of Type II EC.
      These results suggest that the Tam-associated ECs are likely to be similar to
      type I EC and will therefore have a more favorable prognosis.

PMID- 10940496
TI  - Metallothionein induction in islets of Langerhans and insulinoma cells.
AB  - Isolated pancreatic islets from rat and mouse and the insulinoma cell lines,
      betaHC9 and RINm5F, were investigated to determine the regulation of
      metallothionein (MT). Dexamethasone (DEX) increased rat and mouse islet and
      insulinoma cell MT levels in a time- and concentration-dependent manner. Rat
      islet MT expression was increased with interleukin-1beta (IL-1beta), but not
      tumor necrosis factor-alpha (TNF). However, MT induction by IL-1beta and TNF was
      synergistic with DEX in rat islets and insulinoma cells. Mouse islet MT failed to
      respond to IL-1beta alone, although IL-1beta and TNF were synergistic. IL-1beta
      and TNF did not synergize with DEX for mouse islet MT induction. Zinc sulfate
      induced MT in rat islets but not mouse islets. MT messenger RNA levels were
      significantly increased in rat islets in response to DEX and IL-1beta plus DEX.
      The inducible nitric oxide synthase inhibitors N(G)-monomethyl-L-arginine and
      aminoguanidine failed to inhibit IL-1beta induced MT levels in insulinoma cells,
      and the nitric oxide generating agent sodium nitroprusside failed to
      significantly affect MT levels. Phorbol dibutyrate increased MT levels in rat
      islets and betaHC9 cells, but phorbol dibutyrate and IL-1beta effects were not
      additive. Transgenic MT-null and wild-type mouse islets had similar insulin
      contents, but basal and glucose-stimulated insulin release from MT-null islets
      were significantly lower than in wild-type islets. Blood glucose levels in MT
      null mice were, however, slightly lower than those in wild-type mice. Thus, MT
      induction in pancreatic islets and beta-cells is regulated by cytokines and DEX,
      and protein kinase C activation may play a role. However, regulation of MT
      induction in mouse and rat islets differs. MT also appears to modulate insulin
      release from pancreatic islets.

PMID- 10940497
TI  - Isolation and characterization of the 5'-upstream and untranslated regions of the
      mouse type II iodothyronine deiodinase gene.
AB  - The type II iodothyronine deiodinase (D2) catalyzes the 5'-deiodination of
      thyroxine to yield the biologically active form, 3,3',5,-tri-iodothyronine, and
      is a member of the selenoproteins. We isolated a 17.5 kb mouse genomic clone
      containing the entire coding and 5'-untranslated regions of the D2 gene (mdio2).
      We also isolated the entire 5'-UTR of the mouse D2 cDNA, which was 753 bp in
      length and contained five ATG codons. An additional 258 bp ORF from the fourth
      ATG codon was found in the same reading frame as the coding region reported
      previously, and this additional ORF contained a TGA codon, which could encode
      selenocysteine. The proximal promoter of mdio2 contained a TATA box and several
      potential transcription factor-binding sequences, including CRE, C/EBP and GATA
      binding sites. The 1.3 kb 5'-upstream region exhibited a promoter activity by
      reporter assay using Mm5MT and JAR cells, which have a D2 transcript, but not
      HepG2 cells that have no detectable level of D2 transcript.

PMID- 10940498
TI  - The antiestrogen ICI 182,780 inhibits proliferation of human breast cancer cells
      by interfering with multiple, sequential estrogen-regulated processes required
      for cell cycle completion.
AB  - Antiestrogens are widely used for breast cancer treatment, where they act
      primarily by inhibiting the mitogenic action of estrogens on tumor cells. The
      effects of the pure antiestrogen ICI 182,780 on estrogen-regulated cell cycle
      phase-specific events were investigated here in synchronously cycling human
      breast cancer (HBC) cells. In early G(1)-arrested MCF-7 or ZR-75.1 cells, 17beta
      estradiol (E2) induces rapid activation of the cyclin/Cdk/pRb pathway, as
      demonstrated by D-type G(1) cyclins accumulation during the first few hours of
      hormonal stimulation, followed by sequential accumulation of E, A and B1 cyclins
      and progressive pRb phosphorylation, as cells progress through the cell cycle.
      When added to quiescent cells together with E2, ICI 182,780 prevents all of the
      above hormonal effects. Interestingly, in mid-G(1) cells (2-8 h into estrogen
      stimulation) the antiestrogen causes rapid reversal of hormone-induced D-type
      cyclins accumulation and pRb phosphorylation, and still fully inhibits G(1)-S
      transition rate, while in late-G(1) cells it does not prevent S phase entry but
      still inhibits significantly DNA synthesis rate, S-phase cyclins accumulation and
      pRb hyperphosphorylation. These results indicate that pure antiestrogens prevent
      multiple estrogen-induced cell cycle-regulatory events, each timed to allow
      efficient G(1) completion, G(1)-S transition, DNA synthesis and cell cycle
      completion.

PMID- 10940499
TI  - Characterization of the gene encoding both growth hormone-releasing hormone (GRF)
      and pituitary adenylate cyclase-activating polypeptide (PACAP) in the zebrafish.
AB  - The purpose of this research was to isolate and characterize the gene encoding
      growth hormone-releasing hormone (GRF) and pituitary adenylate cyclase-activating
      polypeptide (PACAP) from the zebrafish. The gene is comprised of five exons with
      two distinct peptides encoded on separate exons, GRF on exon 4 and PACAP on exon
      5. Our evidence indicates that the zebrafish genome contains a single copy of the
      GRF-PACAP gene. The tissue distribution pattern of the mRNA transcript shows
      expression in the brain, eye, gastrointestinal tract, ovary and testis; each
      transcript was sequenced and found to be identical to the gene. This is the first
      report of GRF-PACAP mRNA expression in the eye of a non-mammalian species.
      Evidence that a duplication of the PACAP gene gave rise to the vasoactive
      intestinal peptide (VIP) gene is supported by the high amino acid sequence
      identity between PACAP in zebrafish and VIP in other fish species.

PMID- 10940500
TI  - Tissue-specific corticosteroidogenesis in the rat.
AB  - The steroid aldosterone plays a major role in the maintenance of total body
      sodium homeostasis and also contributes to cardiovascular pathophysiology by
      mediating cardiac hypertrophy and fibrosis. In addition to classical adrenal
      production of aldosterone, endogenous tissue production of aldosterone has been
      observed in various organs; aldosterone biosynthesis in cardiac tissues, however,
      remains highly controversial. The current study provides a comprehensive
      evaluation of steroid hormone biosynthethic capabilities in multiple tissues from
      two distinct rat strains under unstimulated and stimulated conditions. Panels of
      tissues from Wistar and Sprague-Dawley rats were probed for 11 beta-hydroxylase
      (P45011beta) and aldosterone synthase (P450aldo) by reverse transcriptase
      polymerase chain reaction (RT-PCR). Under unstimulated conditions, cardiac
      P45011beta and P450aldo were detected only in Wistar rats. Angiotensin II (100
      microg/day) stimulated myocardial expression of both enzymes in both strains.
      Cerebral cortex and mesenteric artery message levels in both strains was reduced
      by angiotensin II. These data demonstrate the potential for local steroid
      synthesis in vascular, cardiac, renal, and neuronal tissues, and that
      biosynthesis of non-adrenal aldosterone may be differentially regulated between
      strains. This variability may thus resolve in part or whole the current
      controversy over the existence of non-adrenal steroidogenic systems.

PMID- 10940501
TI  - Effects of retinoids on the meiosis in the fetal rat ovary in culture.
AB  - We investigated the effect of retinoids on the entrance of female germ cells into
      meiotic prophase and their progression through it, using explants of rat ovaries
      from 14.5 days post coitum (dpc) fetuses cultured with or without 10(-6) M
      retinoic acid (RA) or 10(-9) M retinoic acid receptor alpha (RARalpha) specific
      agonist. The percentages of oogonia and of oocytes at each meiotic stage in the
      ovary were evaluated at explantation (D0) and after 3 (D3), 5 (D5) and 9 (D9)
      days of culture and on equivalent stages in vivo (i. e. 17.5 and 23.5 dpc). The
      number of germ cells per ovary were counted at D0, D3 and D9. Newly explanted
      (D0) ovaries contained no germ cell in meiosis. In control medium some germ cells
      had spontaneously reached the stage leptotene and very few the zygotene on D3.
      The first pachytene were observed on D5 and the first diplotene on D9. This
      pattern mimicked that which occurs in vivo although with a slight delay. RA
      reduced the percentage of oogonia by more than half and increased the percentage
      of zygotene by more than 22-fold on D3, showing that it accelerated entrance into
      meiosis. This effect was also observed in response to RARalpha agonist. RA
      increased the percentage of zygotene and reduced the percentage of pachytene on
      D9, showing that it can also delay the zygotene/pachytene transition. Lastly, RA
      reduced the total number of germ cells present on D3 but not on D9. This may be
      the result of a double effect of RA on the number of germ cells: negative when
      the cells are in proliferation (D0 to D3) and positive when they entered in
      meiotic prophase (after D3). Thus, RA is a potential regulator of germ cells
      meiosis and number in the fetal ovary.

PMID- 10940502
TI  - Differences of four catechins in cell cycle arrest and induction of apoptosis in
      LoVo cells.
AB  - (-)-Epigallocatechin-3-gallate (EGCG), (-)-epigallocatechin (EGC), (-)
      epicatechin-3-gallate (ECG), and (-)-epicatechin (EC) were found to have
      different cytotoxicities to human colon carcinoma LoVo cells. EGCG and EGC
      suppressed the growth of LoVo cells in dose-dependent manner; ECG and EC,
      however, had no obvious effects. At lower concentrations, EC did seem to promote
      slight proliferation. Similarly, EGCG and EGC, rather than ECG and EC, were found
      to induce apoptosis in LoVo cells. Moreover, EGCG, EGC, and ECG arrested G(1)
      phase in the cell cycle progression, whereas EC resulted in S phase arrest. We
      suggest that there are differences in the cytotoxicities of the four catechins to
      LoVo cells. They exert the effects by inducing apoptosis and regulating the cell
      cycle.

PMID- 10940503
TI  - The glutathione-related detoxification pathway in the human breast: a highly
      coordinated system disrupted in the tumour tissues.
AB  - Glutathione and the associated enzymes, glutathione S-transferases, peroxidases,
      and reductase, have been implicated in cancer chemoresistance. This pathway was
      investigated in paired cancerous and peritumoral breast samples from 41 women.
      The tumours exhibited a higher redox status as deduced from increased
      transferase, peroxidase, and reductase activities and from higher total and
      reduced glutathione contents. Several components were strongly correlated in
      peritumoral tissues, suggesting a highly co-ordinated glutathione pathway that
      appeared disrupted in breast tumours with only a few correlations left.
      Therefore, resistance could spontaneously result from deregulated variations in
      the glutathione pathway, which might be relevant to the malignant disease
      progression.

PMID- 10940504
TI  - High mobility group 1 and 2 proteins bind preferentially to DNA that contains
      bulky adducts induced by benzo[a]pyrene diol epoxide and N-acetoxy
      acetylaminofluorene.
AB  - High mobility group (HMG) proteins 1 and 2 are abundant non-histone chromosomal
      proteins that bind preferentially DNA that is bent or underwound. Previous
      studies have shown that these proteins preferentially bind to DNA damaged by the
      crosslinking agents cis-diammine-dichloro-platinum(II), chromium(III) and UV-C
      radiation. Here we have studied the binding of HMG-1/2 proteins to a duplex
      oligonucleotide damaged by benzo(a)pyrene diol epoxide or N-acetoxy
      acetylaminofluorene using an electrophoretic mobility shift assay. Both chemicals
      induce monoadducts that are known to distort DNA structure. The affinities of HMG
      1/2 for DNA damaged by benzo[a]pyrene diol epoxide or N-acetoxy
      acetylaminofluorene were similar to that for UV-irradiated DNA, which were an
      order of magnitude higher than for undamaged DNA. In contrast, DNA modified by
      dimethyl sulfate was not preferentially recognised by HMG-1/2.

PMID- 10940505
TI  - p53 gene mutations in Bowen's disease in Koreans: clustering in exon 5 and
      multiple mutations.
AB  - We analyzed the p53 protein expression and gene mutations to evaluate the role of
      ultraviolet radiation or other carcinogens, and possible racial differences in 17
      samples from 12 Korean patients with Bowen's disease. A simple microdissection
      technique was used to collect the tumor cells selectively. p53 protein expression
      was found in eight of 17 (47%) samples. Abnormalities in polymerase chain
      reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis were
      observed in 16 (94%) samples. A total of 14 missense mutations were detected in
      eight (47%) samples; 11 were clustered in exon 5 and the remaining three were
      located in exon 8. UV-like mutations were seen in five of 14 (36%) mutations, but
      no CC to TT transitions, UV-fingerprint mutations were observed. Multiple
      mutations were present in two cases and double mutation in a single case. Each
      lesion in multiple Bowen's disease showed different mutations and was suggested
      to be of different clonal origins. TP53-loss of heterozygosity (LOH) was detected
      in four out of 15 (27%) informative samples. Clustering of mutations in exon 5
      suggests the role of another carcinogen in Koreans or Asians other than the UVR.
      Microdissection would increase the detection rate of the p53 gene mutations and
      LOH not only in skin cancer but also in precancerous lesions.

PMID- 10940506
TI  - Anticachectic effects of Coptidis rhizoma, an anti-inflammatory herb, on
      esophageal cancer cells that produce interleukin 6.
AB  - Herbs as alternative cancer therapies have attracted a great deal of recent
      attention due to their low toxicity and costs. In this study, the antitumor
      activity and anticachectic effect of Coptidis rhizoma, an anti-inflammatory herb,
      were investigated in nude mice carrying a human esophageal cancer cell line YES
      2, which constitutively secretes interleukin-6 (IL-6) and induces cachexia when
      injected into these mice. In this study, in vivo growth of YES-2 cells was not
      affected by an oral supplement containing the extract powder of C. rhizoma at a
      final concentration of 1% (CR supplement). However, in comparison with normal
      diet, CR supplement significantly attenuated weight loss of tumor-bearing mice
      without a change in food or water intake. Tumor IL-6 levels were significantly
      lower in mice treated with CR supplement than in control mice (P<0.001). Serum IL
      6 was detectable in four (50%) of eight control mice; IL-6 was not detected in
      mice treated with CR supplement. We also confirmed that berberine (8-32 microM),
      a major component of C. rhizoma, dose-dependently inhibited secretion of IL-6 by
      YES-2 cells in vitro. Moreover, reverse transcription-PCR assay showed that
      treatment of YES-2 cells with berberine (8-32 microM) for 24 h reduced IL-6 mRNA
      expression. Our results suggest that C. rhizoma may have an anticachectic effect
      on esophageal cancer and an effect is associated with the ability of berberine to
      down-regulate tumor IL-6 production.

PMID- 10940507
TI  - The glutathione S-transferase mu polymorphism and susceptibility to acute
      lymphocytic leukemia.
AB  - It has been postulated that the absence of glutathione S-transferase mu (GSTmu),
      which impairs detoxification of some carcinogens, might predispose some
      individuals to the development of certain cancers. In the present study,
      polymorphism of GSTM1 were detected by polymerase chain reaction (PCR) in 38
      patients with acute lymphocytic leukemia and 75 normal subjects. The null
      genotype of GSTM1 was significantly more common among leukemic patients compared
      with the normal control group (55.3 vs. 32.0%; P<0.025). The absence of the GSTmu
      enzyme may increase the risk of the development of leukemia.

PMID- 10940508
TI  - Dermal toxicity of topical (-)epigallocatechin-3-gallate in BALB/c and SKH1 mice.
AB  - (-)Epigallocatechin-3-gallate (EGCG), the major polyphenolic component of green
      tea, inhibits experimental chemical and physical carcinogenesis, yet little
      toxicological data has been reported. Therefore, we performed studies on the
      dermal toxicity of EGCG applied in an ointment formulation in mice. Female BALB/c
      mice were dehaired with a topical depilatory and administered 75 microl EGCG in
      hydrophilic Ointment U.S.P. at three concentrations (10, 3, and 1%, all w/w)
      daily for 30 days. At the 10% concentration, gross toxicity was manifested by the
      formation of erythema and papular lesions by day 5. A 7% reduction in weight was
      observed by day 15. No toxicity was observed at the two lower concentrations or
      in the vehicle control group. Also, no toxicity was observed when mice were
      dehaired by shaving. This study was repeated in female SKH1 mice, an outbred
      hairless strain that does not require depilation. No toxicity was observed in the
      SKH1 mice, indicating that daily topical EGCG appears non-toxic in normal skin.
      However, use of topical depilatories may potentiate dermal toxicity of EGCG.

PMID- 10940509
TI  - Anti-tumor-promoting activity of lignans from the aerial part of Saussurea
      medusa.
AB  - In the course of our continuing search for novel cancer chemopreventive agents
      from natural sources, several kinds of Compositae plants were screened.
      Consequently, the lignans, arctiin (ARC) and arctigenin (ARC-G), were obtained
      from the aerial part of Saussurea medusaas active constituents. These compounds
      exhibited the remarkable anti-tumor-promoting effect on two-stage carcinogenesis
      test of mouse skin tumors induced by 7, 12-dimethylbenz[a]anthracene as an
      initiator and 12-O-tetradecanoyl phorbol-13-acetate as a promoter by both topical
      application and oral administration. Furthermore, ARC-G exhibited potent anti
      tumor-promoting activity on two-stage carcinogenesis test of mouse pulmonary
      tumors induced by 4-nitroquinoline-N-oxide as an initiator and glycerol as a
      promoter.

PMID- 10940510
TI  - Serum alpha-N-acetylgalactosaminidase is associated with diagnosis/prognosis of
      patients with squamous cell carcinoma of the uterine cervix.
AB  - Serum alpha-N-acetylgalactosaminidase (NaGalase) is responsible for the
      deglycosylation of vitamin D(3)-binding protein (Gc protein). The deglycosylated
      Gc protein cannot be converted into major macrophage-activating factor (MAF),
      leading to immunosuppression. NaGalase is universally detected in a variety of
      cancer patients, but not in healthy individuals (Cancer Res. 56 (1997) 2827
      2831). However, the diagnostic/prognostic utility of NaGalase in squamous cell
      carcinoma (SCC) of the uterine cervix is not known. To address this issue, the
      serum NaGalase was quantitatively determined in 210 patients with different
      stages of SCC of the uterine cervix. NaGalase levels were increased with the
      progression of the cancer. After radiotherapy, the increased levels returned
      toward or to normal levels in early stages (FIGO stage I-IIB) but not in advanced
      stages (FIGO stage III-IV). The present study revealed that the amount of
      NaGalase in the patient's bloodstream reflects the tumor burden and
      aggressiveness of the disease. We conclude that NaGalase is an independent
      predictor of diagnosis/prognosis in SCC of the uterine cervix, and therefore
      suggest that quantitative NaGalase alteration may reflect important differences
      in the immunological functions of these neoplasms.

PMID- 10940511
TI  - Chromosome aberrations as a predictor of clinical outcome for smoking associated
      lung cancer.
AB  - The ability to identify individuals at greatest risk of developing lung cancer
      can significantly enhance the efficacy of intervention modalities. One strategy
      for identifying these individuals is through biomarkers that reflect the severity
      of their cancer. In the present study, we evaluated 22 lung cancer patients and
      35 controls to determine whether the frequency of chromosome aberrations was
      significantly associated with specific clinical variables such as the
      histological type, grade and stage of the tumors. Chromosome aberrations
      (expressed as total breaks) were investigated on chromosome 1 in interphase
      nuclei obtained from blood lymphocytes of the study participants using the
      fluorescence in situ hybridization (FISH) chromosome aberration assay. Our
      results indicate a significant linear increase (P=0.01) in the level of breaks
      with respect to the grade of the carcinoma. The poorly differentiated tumors had
      a significantly higher level of chromosome breaks mean+/-SD (1.7+/-0.46) as
      compared to the well differentiated tumors (0.98+/-0.23, P<0.05). These results
      indicate that chromosome aberrations, as determined by the FISH assay, can be
      used as a biomarker for identifying individuals with aggressive types of lung
      cancer and potentially, as a predictor for prognostic outcome of the disease.

PMID- 10940512
TI  - Sustained nuclear localization of p21/WAF-1 upon growth arrest induced by contact
      inhibition.
AB  - We assessed the expression and distribution of p21/Waf-1 in TLM1 melanoma cells
      that exhibit contact inhibition and require serum for growth. The growth stage of
      cells stimulated to enter the mitotic cell cycle synchronously and grow to
      confluence was characterized by distinct, yet consistent levels and patterns of
      distribution of p21/Waf-1. Significantly, sustained accumulation of p21/Waf-1 in
      the nuclear compartment was seen only after 4 days in culture when cell-to-cell
      contacts were established, leading to a diminished rate of cell growth.
      Overexpression of wild-type waf-1 in melanoma cells reduced growth of
      subconfluent cells, decreased Cdk4 activity with a concomitant increase in
      hypophosphorylated Rb, and promoted cell death by apoptosis. The data support the
      premise that cell-to-cell contacts provide signals that mediate sustained nuclear
      localization of p21/Waf-1 leading to cell growth arrest; furthermore, an
      elevation in the activity of this protein can lead to apoptosis.

PMID- 10940513
TI  - Anti-proliferative effect of resveratrol, a natural component of grapes and wine,
      on human colonic cancer cells.
AB  - Resveratrol, a natural polyphenolic phytoalexine present in grapes and wines, has
      been reported to exert a variety of important pharmacological effects. We
      investigated the effects of resveratrol on the growth and polyamine metabolism of
      CaCo-2 human colon cancer cells. Treatment of the CaCo-2 cells with 25 microM
      resveratrol caused a 70% growth inhibition. The cells accumulated at the S/G2
      phase transition of the cell cycle. No signs of cytotoxicity or apoptosis were
      detected. Resveratrol caused a significant decrease of ornithine decarboxylase
      (ODC) activity, a key enzyme of polyamine biosynthesis, which is enhanced in
      cancer growth. ODC inhibition resulted in the reduction of the intracellular
      putrescine content, indicating that polyamines might represent one of several
      targets involved in the anti-proliferative effects of resveratrol.

PMID- 10940515
TI  - Interferon treatment of uterine cervical carcinoma: 20 years of follow-up.
AB  - Twenty-seven randomized patients with biopsy proven carcinoma of the uterine
      cervix were treated with human natural leucocytic interferon (HNLI) and followed
      up, while 30 randomized patients were followed up in the control group and were
      not treated with HNLI. International Federation of Gynecology and Obstetrics
      (FIGO) classification of HNLI-treated patients was IA: 8, IB: 9, IIA and IIB: 10.
      FIGO classification of control non-treated patients was IA: 9, IB: 10, IIA and
      IIB: 12. HNLI was applied locally at 2x10(6) U daily in pessaries for 21 days
      before surgery. Survival analysis of the HNLI-treated patients after 240 months
      of observation showed that 20 patients (74.07%) out of 27 survived, and in the
      control group 14 patients (46.67%) out of 30 survived. Statistical difference
      between the HNLI-treated group and control group of patients is significant
      P<0.05.

PMID- 10940514
TI  - A new assay for lipiodol in a tumor using a combination of m-chloroperbenzoic
      acid-mediated oxidation and the iodo-starch reaction.
AB  - Lipiodol, an iodine adduct lipid, has been used as a targeting carrier of
      anticancer drugs in experimental animals and humans. In most studies, the
      concentrations of the anticancer drugs in tissues and organs have been monitored,
      but not of the carrier because a simple method for measuring lipiodol in
      biological organs did not exist. Here we present an analytical method for the
      quantitative determination of lipiodol in tissue. This method is based on the
      measurement of iodine released from lipiodol by an oxidative reaction. The
      released iodine was measured spectrophotometrically by monitoring the iodo-starch
      reaction. Using this method, we were able to demonstrate the tumor specificity of
      lipiodol using rabbits bearing VX2 tumors in the liver. The present method is
      also expected to be applicable to human cancers, such as hepatic and colon
      cancer.

PMID- 10940516
TI  - The Akt/protein kinase B-dependent anti-apoptotic pathway and the mitogen
      activated protein kinase cascade are alternatively activated in human
      glioblastoma multiforme.
AB  - We investigated the activation of two important signal transduction pathways in
      human glioblastoma cells and found a constitutive phosphorylation of either Akt
      or mitogen-activated protein kinase (MAPK) under serum free conditions. In all
      but one cell line Wortmannin-sensitive activation of Akt could be attributed to
      the loss of functional PTEN protein. All cell lines with Akt activation exhibited
      only weak phosphorylation of the MAPK signal pathway, whereas those without
      constitutive Akt activation demonstrated high levels of phosphorylated MAPK under
      serum free conditions. Our data might indicate the presence of two functional
      subtypes of glioblastoma multiforme, since Akt and MAPK are involved in cellular
      survival and proliferation signalling, respectively.

PMID- 10940518
TI  - Selamectin - a novel endectocide for dogs and cats.

PMID- 10940519
TI  - Selamectin: a novel broad-spectrum endectocide for dogs and cats.
AB  - Selamectin, 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy-22, 23-dihydro-5
      (hydroxyimino)-avermectin B1 monosaccharide, is a novel endectocide with a unique
      combination of efficacy and safety in dogs and cats following both oral and
      topical administration. The compound is active against fleas and ticks,
      intestinal hookworms and ascarids, and immature heartworms. Also it is well
      tolerated at higher dosages than 22,23-dihydroavermectin B1a (DHAVM) or
      milbemycin oxime in Collies, which is a breed known to exhibit idiosyncratic
      sensitivity to avermectins.

PMID- 10940520
TI  - Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides
      felis felis) on dogs and cats.
AB  - Selamectin, a novel avermectin, was evaluated in two controlled studies (one in
      Beagles, one in domestic shorthaired cats) to determine an appropriate topical
      dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on
      dogs and cats for 1 month. For each study, animals were allocated randomly to
      four treatments. One treatment consisted of the inert formulation ingredients
      (vehicle) administered as a negative control, and the other three treatments
      consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each
      study, selamectin was administered as a topical dose applied to the skin in a
      single spot at the base of the neck in front of the scapulae. Dogs and cats were
      infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11,
      18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21,
      and 30, a comb count to determine the number of viable fleas present on each
      animal was performed. Efficacy of selamectin on day 30 was used to select an
      appropriate dose. For dogs and cats, percentage reductions in geometric mean flea
      comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days
      7, 14, and 21, compared with the negative-control treatment. On day 30,
      reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8,
      98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1),
      respectively. For day 30 flea comb counts for dogs and cats, analysis of variance
      showed that the three selamectin treatments resulted in significantly (P< or
      =0.05) lower counts than did the negative-control treatment. For dogs and cats,
      geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1)
      were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1)
      treatment dosages combined. There were no significant differences in flea counts
      between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear
      plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult
      fleas for both dogs and cats, as estimated by the turning point (plateau) in the
      dose response curve, was 6mgkg(-1).

PMID- 10940521
TI  - Efficacy of selamectin against adult flea infestations (Ctenocephalides felis
      felis and Ctenocephalides canis) on dogs and cats.
AB  - Selamectin was evaluated in eight controlled studies (4 in dogs, 4 in cats) to
      determine the efficacy of a single topical unit dose providing the recommended
      minimum dosage of 6mgkg(-1) against Ctenocephalides felis felis and
      Ctenocephalides canis fleas on dogs and against C. felis on cats. In addition,
      the effect of bathing on the efficacy of selamectin against C. felis was
      evaluated. Identical studies were performed in Beagles and domestic shorthaired
      cats. For each study, animals were allocated randomly to treatments of 8-12
      animals each. All studies (dog studies A, B, C, and D and cat studies A, B, C,
      and D) evaluated the efficacy of selamectin without bathing. In addition, study C
      in both dogs and cats evaluated efficacy with a shampoo bath at 24h after dosing,
      and study D evaluated the efficacy of selamectin with water soaking at 2h after
      dosing or with a shampoo bath at 2-6h after dosing. Dog study B evaluated
      efficacy against C. canis, whereas all other studies used C. felis. In each
      study, selamectin was administered on day 0 as a topical dose that was applied
      directly to the skin in a single spot at the base of the neck in front of the
      scapulae. Dogs and cats were infested with approximately 100 viable unfed C.
      felis or C. canis on days 4, 11, 18, and 27. On days 7, 14, 21, and 30,
      approximately 72h after infestation, a comb count of the number of viable fleas
      present on each animal was made. For C. felis and C. canis for dogs and cats,
      compared with controls, selamectin achieved significant reductions in geometric
      mean adult flea comb counts of > or =98.9% on days 7, 14, and 21 in all eight
      studies. On day 30, the reduction for C. felis remained at or above 98.0%. This
      included the dogs and cats that were soaked with water or bathed with shampoo at
      2, 6, or 24h after treatment. There were no significant (P>0.05) differences
      between the flea counts from selamectin-treated animals in these studies,
      regardless of bathing status. On day 30, a significant reduction of 91.8% was
      achieved against C. canis on dogs. Thus, these studies demonstrated that a single
      topical unit dose of selamectin was highly effective against adult fleas on dogs
      and cats for at least 27 days.

PMID- 10940523
TI  - Efficacy of selamectin in the treatment and prevention of flea (Ctenocephalides
      felis felis) infestations on dogs and cats housed in simulated home environments.
AB  - The efficacy of selamectin, a novel avermectin, in protecting dogs and cats
      against experimentally induced environmental flea (Ctenocephalides felis felis)
      infestations, was evaluated in a series of controlled and masked studies. Purpose
      bred shorthaired cats and Beagles were randomly allocated to treatment with
      either selamectin at a minimum dosage of 6mgkg(-1) of body weight in the
      commercial formulation or the negative control treatment (vehicle only), and
      housed in controlled simulated home environments capable of supporting the flea
      life cycle. Day 0 was defined as the first day of treatment. Treatments were
      administered topically in a single spot on the skin at the base of the neck in
      front of the scapulae. In environmental challenge studies, which were designed to
      evaluate the efficacy of selamectin in the treatment and control of established
      flea infestations, dogs and cats were each infested with 100 fleas on days -28
      and -21 and placed in carpeted rooms in order to establish high levels of active
      flea infestation prior to day 0. Treatments were administered monthly for 3
      months. Flea comb counts were performed on days 14, 29, 44, 59, 74, and 90.
      Reductions in geometric mean flea comb counts for selamectin, compared with
      vehicle, were >99% from day 14 onwards for dogs, and >92% on day 29 and >99% on
      days 44, 59, 74, and 90 for cats (P=0.0001). In prevention of environmental
      infestation studies, dogs and cats were placed in environments capable of
      supporting flea infestations and given monthly treatments for 2 months,
      commencing on day 0. Animals were infested with 100 fleas on days 1 and 7, and
      flea comb counts were performed on days 29, 44, and 60. Reductions in geometric
      mean flea comb counts for selamectin, compared with vehicle, were >99% on days
      29, 44, and 60 (P=0.0001) for dogs and cats. Monthly administration of selamectin
      to dogs and cats housed in environments highly suited to completion of the flea
      life cycle was shown to be highly effective in the treatment and prevention of
      flea infestations, without the need for supplementary environmental control
      measures.

PMID- 10940522
TI  - Evaluation of the effects of selamectin against adult and immature stages of
      fleas (Ctenocephalides felis felis) on dogs and cats.
AB  - The adulticidal, ovicidal, and larvicidal effects of selamectin against flea
      (Ctenocephalides felis felis) infestations on dogs and cats were evaluated in a
      series of seven controlled and masked studies (three in cats, four in dogs).
      Animals were randomly allocated to treatment with either selamectin at a minimum
      dosage of 6mgkg(-1) in the commercial formulation or one of two negative-controls
      (0.9% NaCl solution or the vehicle from the commercial formulation). Treatments
      were administered topically in a single spot on the skin at the base of the neck
      in front of the scapulae. Speed of kill, measured by flea comb counts at 12h
      intervals during the 48h immediately following a single treatment on day 0, was
      evaluated in two studies. One study was in dogs and the other in cats, and each
      animal was infested with approximately 100 unfed viable adult fleas prior to
      treatment. Reductions in geometric mean flea counts for selamectin compared with
      saline were >98% between 24 and 36h after treatment in dogs, and between 12 and
      24h after treatment in cats (P< or =0.0006). Efficacy in reducing flea egg hatch
      and larval development was evaluated in four studies, in which dogs and cats were
      treated once on day 0 and then repeatedly infested with approximately 600 fleas.
      Flea eggs were collected approximately for 72h after each infestation, on days 3,
      7, 14, 21, and 30, counted, and cultured to determine their hatchability and
      subsequent larval development. Compared with the vehicle, selamectin was highly
      effective in reducing flea egg hatch (>92% in cats) and larval development (> or
      =95% for dogs and cats), and emergence of adults (97.8-100% for dogs, 85.6-100%
      for cats) for 30 days. Effects of exposure to hair coat debris were investigated
      in a study with dogs treated once on day 0 and repeatedly infested with 100 adult
      fleas. Debris (dander, flea faeces, hair, scales) was collected on days 1, 7, 14,
      21, and 30 and added to normal flea eggs or larvae for incubation. Compared with
      debris from vehicle-treated dogs, debris from selamectin-treated dogs was highly
      effective in preventing egg hatch (>96%), in killing larvae (>98%) and in
      preventing larval development to adults (>99%) (P</=0.0033). Selamectin was shown
      to be highly effective in the treatment and control of flea infestations (C.
      felis) on dogs and cats. The adulticidal, ovicidal, and larvicidal effects of
      selamectin will be important in interrupting the flea life cycle by preventing
      the introduction and establishment of new flea infestations in a household
      environment.

PMID- 10940524
TI  - Efficacy and safety of selamectin against fleas on dogs and cats presented as
      veterinary patients in Europe.
AB  - Two controlled and masked multi-centre studies were conducted to examine the
      efficacy of a novel topical avermectin, selamectin, against natural flea
      infestations on 418 dogs and 345 cats. Veterinary patients with viable flea
      infestations were enrolled in the studies, which were conducted in United
      Kingdom, France, Germany, and Italy. Animals were allocated randomly in a 2:1
      ratio to one of two treatments: either selamectin alone at a minimum dosage of
      6mgkg(-1) or fenthion at recommended dose rates. Concurrent use of an
      environmental spray (containing methoprene and either pyrethrins or permethrin)
      was permitted only for fenthion-treated animals. In-contact cats and dogs
      (animals living in the same home) received the same treatment as the first animal
      enrolled from the household, if recommended by the veterinarian. Study day 0 was
      defined as the day of first treatment. Animals were treated on days 0, 30, and
      60, and flea comb counts and clinical evaluations were conducted on days 0, 14,
      30, 60, and 90. Analysis of variance of ln(flea count+1) showed that values were
      significantly lower for selamectin alone compared with fenthion (with or without
      the concurrent use of an environmental spray) in dogs on days 30, 60, and 90
      (P<0.05) and in cats on days 14, 30, 60, and 90 (P<0.01). For selamectin, the
      reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared
      with day 0, were 92.5, 90.7, 98.1, and 99.1%, respectively, for dogs and 92.8,
      92.7, 97.7, and 98.4%, respectively, for cats. Selamectin was shown to be safe
      and highly effective in the control of naturally acquired flea infestations on
      dogs and cats presented as veterinary patients in Europe.

PMID- 10940526
TI  - Efficacy of selamectin in the prevention of adult heartworm (Dirofilaria immitis)
      infection in dogs in northern Italy.
AB  - The efficacy of a novel avermectin, selamectin, was evaluated for the prevention
      of heartworm disease (adult Dirofilaria immitis infection) in 120 dogs (aged 9
      months to 13 years at enrolment) presented as veterinary patients. The study was
      conducted at five veterinary practices in a heartworm hyperendemic region of
      northern Italy. Dogs were allocated randomly in a 2:1 ratio to treatment with
      either selamectin or ivermectin. Treatments were administered at monthly
      intervals for 6 months during the heartworm transmission season (May-November).
      Selamectin was applied topically in a single spot to the skin on each animal's
      back at the base of the neck in front of the scapulae as a unit dose that
      provided at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(
      1)). Ivermectin (6microgkg(-1) of body weight) was administered orally at monthly
      intervals, in accordance with the manufacturer's product label recommendations.
      Study day 0 was defined individually for each dog as the day of first treatment
      administration. Efficacy was assessed on the basis of the absence of D. immitis
      microfilariae and adult heartworm (D. immitis) antigen in tests conducted on days
      180 and 300. There were no adverse clinical signs arising due to treatment with
      selamectin and no drug-related mortalities. The prevention rate for D. immitis
      microfilariae and adult heartworm antigen was 100% for both selamectin and
      ivermectin. Thus, selamectin administered as a unit dose, providing at least the
      recommended minimum dosage of 6mgkg(-1), at monthly intervals during the
      heartworm transmission season was safe and 100% effective in the prevention of
      heartworm disease in dogs presented as veterinary patients.

PMID- 10940525
TI  - Efficacy and safety of selamectin against fleas and heartworms in dogs and cats
      presented as veterinary patients in North America.
AB  - A series of randomized, controlled, masked field studies was conducted to assess
      the efficacy and safety of selamectin in the treatment of flea infestations on
      dogs and cats, and in the prevention of heartworm infection in dogs. In addition,
      observations were made on the beneficial effect of selamectin treatment on dogs
      and cats showing signs of flea allergy dermatitis (FAD). In all studies
      selamectin was applied topically, once per month, in unit doses providing a
      minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea
      infestations, some of which also had signs associated with FAD, were assigned
      randomly to receive three months of topical treatment with selamectin (220 dogs,
      189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins,
      n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as
      the day that the animal first received treatment. Flea burdens were assessed by
      flea comb counts and clinical evaluations of FAD were performed before treatment,
      and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in
      selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea
      counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%,
      respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea
      counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean
      flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%,
      respectively, compared with day 0 counts. Selamectin also was beneficial in
      alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397
      dogs free of adult heartworm infection from four heartworm-endemic areas of the
      USA were allocated randomly to six months of treatment with selamectin (n=298) or
      ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with
      all dogs testing negative for microfilariae and adult heartworm antigen on days
      180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats
      having an age range of 6 weeks to 19 years (3954 doses). The animals included 19
      purebred or crossbred Collies (Bearded, Border, and unspecified). There were no
      serious adverse events. Results of these studies indicated that selamectin was
      highly effective in the control of flea infestations in dogs and cats without the
      need for simultaneous treatment of the environment or of in-contact animals and
      also was beneficial in alleviating signs associated with FAD. Selamectin also was
      100% effective in preventing the development of canine heartworms and was safe
      for topical use in dogs and cats.

PMID- 10940527
TI  - Prevention of experimentally induced heartworm (Dirofilaria immitis) infections
      in dogs and cats with a single topical application of selamectin.
AB  - In a series of six controlled studies (four in dogs, two in cats), heartworm-free
      dogs and cats were inoculated with Dirofilaria immitis larvae (L(3)) prior to
      topical treatment with the novel avermectin selamectin or a negative control
      containing inert formulation ingredients (vehicle). Selamectin and negative
      control treatments were administered topically to the skin at the base of the
      neck in front of the scapulae. In dogs, selamectin was applied topically at
      dosages of 3 or 6mgkg(-1) at 30 days post-inoculation (PI), or of 3 or 6mgkg(-1)
      at 45 days PI, or of 6mgkg(-1) at 60 days PI. Cats were treated topically with
      unit doses providing a minimum dosage of 6mgkg(-1) selamectin at 30 days PI. Of
      the animals that were treated 30 days PI, some dogs were bathed with water or
      shampoo between 2 and 96h after treatment, and some cats were bathed with shampoo
      at 24h after treatment. Between 140 and 199 days PI, the animals were euthanized
      and examined for adult D. immitis. Adult heartworms developed in all control dogs
      (geometric mean count, 18.7 worms) and in 88% of control cats (geometric mean
      count, 2.1 worms). Selamectin was 100% effective in preventing heartworm
      development in dogs when administered as a single topical dose of 3 or 6mgkg(-1)
      at 30 days after infection, 3 or 6mgkg(-1) at 45 days after infection, or 6mgkg(
      1) at 60 days after infection. Selamectin was 100% effective against heartworm
      infections in cats when administered as a single topical unit dose of 6mgkg(-1).
      Bathing with water or shampoo between 2 and 96h after treatment did not reduce
      the efficacy of selamectin as a heartworm prophylactic in dogs. Likewise, bathing
      with shampoo at 24h after treatment did not reduce the efficacy of selamectin in
      cats. These studies demonstrated that, at the recommended dosage and treatment
      interval, a single topical administration of selamectin was 100% effective in
      preventing the development of D. immitis in dogs and cats.

PMID- 10940528
TI  - The efficacy of selamectin in the treatment of naturally acquired infestations of
      sarcoptes scabiei on dogs.
AB  - Selamectin, a novel avermectin, was evaluated for its effect on naturally
      occurring infestations of Sarcoptes scabiei in 42 dogs. In two controlled and
      masked laboratory studies conducted in the USA and Italy, infested dogs received
      treatment with either selamectin (6mgkg(-1); range: 6-12mgkg(-1)) or the vehicle
      only (negative control). Treatments were administered topically to the skin on
      each animal's back at the base of the neck in front of the scapulae. Study day 0
      was defined as the first day of treatment administration. Dogs were treated on
      days 0 and 30, and efficacy was assessed by counting viable mites recovered from
      skin scrapings performed on each dog on days 14, 29 or 30, 44, and 60, and by
      categorising the clinical signs of canine scabies on the same days. Percentage
      reductions in geometric mean mite counts for selamectin, compared with vehicle,
      on days 14, 29 or 30, 44, and 60 were > or =98.1, > or =93.5, 100, and 100%,
      respectively. Analysis of variance, confirmed by Savage Scores, showed that
      ln(mite counts+1) values for selamectin-treated dogs were significantly lower (P<
      or =0.0391) than those for vehicle-treated dogs on all post-treatment assessment
      days. Clinical signs of scabies were markedly reduced in selamectin-treated dogs,
      compared with vehicle-treated dogs. Topical administration to the skin in a
      single spot of a single unit dose of selamectin, or of two unit doses given 1
      month apart, each providing at least the recommended minimum dosage of 6mgkg(-1),
      was highly effective against naturally acquired infestations of S. scabiei in
      dogs, reducing mite counts by >93% (single dose) and 100% (two doses).

PMID- 10940529
TI  - The efficacy of selamectin in the treatment of naturally acquired aural
      infestations of otodectes cynotis on dogs and cats.
AB  - The efficacy of a novel avermectin, selamectin, was evaluated against naturally
      acquired aural infestations of Otodectes cynotis on dogs and cats. In four
      controlled and masked studies conducted in the USA and Europe, animals were
      allocated randomly to treatment with either selamectin at a minimum dosage of
      6mgkg(-1) (range, 6-12. 5mgkg(-1)) or the vehicle only from the commercial
      formulation of selamectin (negative control). Treatments were administered
      topically in a single spot to the skin of each animal's back at the base of the
      neck in front of the scapulae. Cats were treated on day 0 only, and dogs were
      treated either on day 0 only or on days 0 and 30. The ears of dogs were examined
      otoscopically on day 14 for the presence of viable mites. Mite counts were
      conducted on day 30 for animals that had received one dose and on day 60 for
      animals that had received two doses. Percentage reductions in geometric mean mite
      counts for selamectin treatment compared with the vehicle were 100% for all
      animals on all count days. Analysis of variance, confirmed by Savage Scores,
      showed that ln(mite count+1) values were significantly (P< or =0.0015) lower for
      selamectin than for the vehicle for all animals on all count days. Thus,
      selamectin administered topically at a minimum dosage of 6mgkg(-1) was safe and
      100% effective against naturally acquired aural infestations of O. cynotis in
      dogs and cats after a single dose or after two doses administered 1 month apart.

PMID- 10940530
TI  - Efficacy and safety of selamectin against Sarcoptes scabiei on dogs and Otodectes
      cynotis on dogs and cats presented as veterinary patients.
AB  - A series of randomized, controlled and masked field studies was conducted in
      veterinary patients to evaluate the efficacy of selamectin, a novel avermectin,
      in the treatment of naturally occurring Sarcoptes scabiei infestations on dogs
      and Otodectes cynotis infestations on dogs and cats. A total of 342 dogs and 237
      cats participated in these studies, which were conducted at 40 veterinary
      practices in the USA and Europe. Animals were randomly assigned to treatment with
      selamectin or a positive-control product (existing approved products). Selamectin
      was administered as a unit dose providing a minimum of 6mgkg(-1) (range: 6
      12mgkg(-1)) in a topical preparation applied to the skin in a single spot on day
      0 (O. cynotis in cats, n=144), or on days 0 and 30 (O. cynotis and S. scabiei in
      dogs, n=83 and n=122, respectively). The presence of parasites was assessed
      before treatment and at 30 days (for all studies) and 60 days (for O. cynotis and
      S. scabiei dog studies) after first treatment. The animals were also evaluated
      clinically at each assessment period. Based on skin scrapings, the efficacy of
      selamectin against S. scabiei infestations on dogs was >95% by day 30, and 100%
      by day 60. Against O. cynotis, selamectin eliminated mites in 94-100% of cats by
      day 30, and in 90% of dogs by day 60. The positive-control products achieved
      similar results. Thus, selamectin was safe and effective against ear mites in
      dogs and cats and sarcoptic mange in dogs when used in field (veterinary patient)
      studies in dogs and cats of a wide variety of ages and breeds.

PMID- 10940531
TI  - Efficacy of selamectin against experimentally induced and naturally acquired
      infections of Toxocara cati and Ancylostoma tubaeforme in cats.
AB  - The efficacy of selamectin against experimentally induced and naturally acquired
      infections of adult ascarids (Toxocara cati) and adult hookworms (Ancylostoma
      tubaeforme) was evaluated in five controlled studies in cats. Two studies
      evaluated the efficacy of selamectin against both ascarid (natural or induced)
      and hookworm (induced) infections; two studies evaluated the efficacy of
      selamectin against single natural infections of T. cati or A. tubaeforme; and the
      fifth study evaluated the efficacy of selamectin against induced infections of A.
      tubaeforme. Cats received selamectin topically in unit doses designed to deliver
      a minimum of 6mgkg(-1). Treatments were applied to the skin on each animal's back
      at the base of the neck in front of the scapulae. For experimentally induced
      infections, cats were inoculated orally with approximately 500 embryonated eggs
      of T. cati 56 days prior to treatment and/or approximately 150-250 larvae (L(3))
      of A. tubaeforme 30 or 42 days prior to treatment. For both induced and naturally
      acquired infections, cats were allocated randomly to treatments (6-12 cats per
      treatment) on the basis of fecal egg counts to receive either selamectin or a
      vehicle containing the inert formulation ingredients. In all studies, adult worm
      counts were performed at necropsy 14 days after the last treatment
      administration. Against T. cati, a single application of selamectin provided a
      100% reduction in the geometric mean number of adult worms for both
      experimentally induced and naturally acquired infections. Against A. tubaeforme,
      a single administration of selamectin provided a 99.4% reduction in the geometric
      mean number of adult worms in cats with natural infections, and an 84.7-99.7%
      reduction in adult worms in cats with induced infections. Two doses of selamectin
      administered at monthly intervals provided a 91.9% reduction in the geometric
      mean number of adult A. tubaeforme worms in cats with experimentally induced
      infections. The geometric mean numbers of adult worms (T. cati and A. tubaeforme)
      from selamectin-treated cats were significantly (P< or =0.0018) lower than for
      vehicle-treated cats in all studies. Thus, a single topical unit dosage providing
      a minimum dosage of 6mgkg(-1) selamectin was highly effective in the treatment of
      naturally acquired and experimentally induced infections of T. cati and A.
      tubaeforme in cats.

PMID- 10940532
TI  - Efficacy and safety of selamectin against gastrointestinal nematodes in cats
      presented as veterinary patients.
AB  - A series of randomized, controlled, masked, field (veterinary patient) studies
      were conducted in the USA and Europe to evaluate the efficacy of selamectin, a
      novel macrocyclic lactone of the avermectin subclass, in the treatment of
      naturally acquired gastrointestinal nematode infections in cats. After
      confirmation of ascarid and/or hookworm infection, 298 cats of various ages and
      breeds were randomly assigned to treatment with selamectin (n=202) or an existing
      commercially approved positive-control product (n=96). Unit doses of selamectin
      (providing a minimum dosage of 6mgkg(-1)) were administered topically to the skin
      in a single spot at monthly intervals. Quantitative fecal examinations were
      performed on days 0 (before treatment), 30, and 60. In the selamectin-treated
      cats, fecal ascarid egg counts were reduced by 99.6 to 100% on day 30, and by
      99.9 to 100% on day 60. Fecal hookworm egg counts were reduced by 98.3% on day
      30, and by 100% on day 60 in the selamectin-treated cats. The positive-control
      products achieved reductions in egg counts of 96.5 to 100% (ascarids) and 98.9 to
      99.9% (hookworms). These studies have shown that monthly topical administration
      of selamectin is safe and highly effective in the treatment of naturally acquired
      ascarid and hookworm infections in cats.

PMID- 10940533
TI  - Efficacy of selamectin against experimentally induced and naturally acquired
      ascarid (Toxocara canis and Toxascaris leonina) infections in dogs.
AB  - The efficacy of selamectin against adult ascarids was evaluated in eight
      controlled and masked studies in dogs. Three laboratory studies evaluated
      selamectin against experimentally induced infections of Toxocara canis; three
      laboratory studies evaluated selamectin against naturally acquired infections of
      T. canis; one laboratory study evaluated selamectin against naturally acquired
      infections of both T. canis and Toxascaris leonina; one field study evaluated
      selamectin against naturally acquired infections of ascarids (T. canis and/or T.
      leonina) in dogs presented as veterinary patients. Selamectin was administered
      topically to the skin of dogs in unit doses designed to deliver a minimum of
      6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to
      treatment assignments (selamectin or vehicle control in laboratory studies:
      selamectin or reference product in the field study) on the basis of pretreatment
      fecal egg counts. For induced infections, there were significant reductions in
      geometric mean numbers of adult T. canis after a single application of selamectin
      (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or
      =0.0001), and after three monthly applications (100%, P< or =0.0002). In the
      natural infection laboratory studies, when selamectin was administered twice at
      an interval of 30 days, the percentage reductions in geometric mean numbers of
      adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was
      administered on days 0, 14, and 30, the percentage reductions were 91.1 and
      97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P<
      or =0.0067) at the end of the studies. In the field study, geometric mean fecal
      ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days,
      respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001)
      30 days after the second treatment with selamectin. These reductions compared
      favorably with the egg count reductions from dogs treated with a reference
      product containing praziquantel, pyrantel embonate, and febantel. There were no
      adverse drug experiences or treatment-related mortalities during any of the
      studies. Selamectin, when administered topically in a unit dose providing a
      minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T.
      leonina and in reducing the fecal excretion of T. canis eggs in dogs.

PMID- 10940534
TI  - Efficacy of selamectin administered topically to pregnant and lactating female
      dogs in the treatment and prevention of adult roundworm (Toxocara canis)
      infections and flea (Ctenocephalides felis felis) infestations in the dams and
      their pups.
AB  - The efficacy of selamectin in the treatment and prevention of naturally acquired
      Toxocara canis infections and experimentally induced flea (Ctenocephalides felis
      felis) infestations in dams and their suckling pups was evaluated by
      administering selamectin to the adult females only, approximately 40 and 10 days
      before parturition and 10 and 40 days after parturition. Unit doses of the
      commercial formulation of selamectin were administered to the dams to provide at
      least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Dams and
      their pups were housed in carpeted environments able to support the flea life
      cycle. Flea infestations were established initially by experimental infestation
      before treatment administration and by repeated re-infestation of dams at
      approximately weekly intervals throughout the study, which was completed 45 days
      after parturition. There were no adverse drug experiences related to treatment
      with selamectin and no treatment-related mortalities. Percentage reductions in
      geometric mean T. canis faecal egg counts for the selamectin-treated dams,
      compared with those receiving the negative-control treatment (vehicle only) were
      99.7% at the end of the study (P=0.0001). Geometric mean faecal egg counts in
      pups from selamectin-treated females were reduced by > or =96% on the 24th and
      34th days after birth (P=0.0001), and the number of adult worms recovered from
      the gastrointestinal tract of pups from selamectin-treated dams was reduced by
      98.2% (P=0.0001), compared with that for pups from dams treated with the vehicle
      only. Percentage reductions in geometric mean flea counts for selamectin-treated
      dams and their pups, compared with vehicle-treated dams and their pups, were > or
      =99.8% (P=0.0001) and 100% (P=0.0001), respectively, throughout the study. Thus,
      selamectin administered topically at a minimum unit dosage of 6mgkg(-1) to dams
      with naturally acquired T. canis infections and experimentally induced C. felis
      infestations was safe and highly effective in the treatment, control, and
      prevention of adult T. canis infection and C. felis infestation affecting both
      the dams and their pups.

PMID- 10940535
TI  - Efficacy of selamectin against experimentally induced tick (Rhipicephalus
      sanguineus and Dermacentor variabilis) infestations on dogs.
AB  - Seven controlled studies were conducted to investigate the efficacy of selamectin
      against weekly infestations of dogs with Rhipicephalus sanguineus and Dermacentor
      variabilis. Treatments (selamectin or vehicle alone) were applied topically at
      weekly, 2-week, or monthly intervals or in a "Monthly Plus" regimen (monthly
      treatment with an additional treatment at 14 days after the first treatment).
      Selamectin was supplied in unit dose tubes designed to deliver a minimum dosage
      of 6mgkg(-1). The studies ranged in duration from 37 to 90 days. Fifty adult
      ticks (+/-2) were applied approximately weekly, and tick counts were performed 3,
      4, and 5 days after each infestation. The efficacy of selamectin was expressed as
      the percentage reduction in geometric mean tick counts on selamectin-treated dogs
      compared with those for dogs treated with the vehicle alone (negative-control).
      In one study, the engorgement of Dermacentor variabilis was assessed by weighing
      ticks after removal on the fifth day after each infestation. Weekly and 2-week
      interval treatments with selamectin provided efficacies against R. sanguineus of
      >89% across the entire study periods, with 100% efficacy being achieved from 21
      days after the first dose and thereafter (study duration, 37 days for the weekly
      regimen and 44 days for the 2-week interval regimen). D. variabilis also was well
      controlled by the 2-week interval treatment regimen, with >96% efficacy being
      achieved from 21 days after the first treatment and thereafter until the end of
      the study (study duration: 90 days). In five of six studies incorporating three
      treatments at monthly intervals, the percentage reduction in R. sanguineus and D.
      variabilis counts 5 days after infestation ranged from 90 to 100% in the second
      and third months after treatment began. In the sixth study, reductions of > or
      =95% in D. variabilis counts 5 days after infestation were achieved for 2 weeks
      after each treatment in the second and third months. For the Monthly Plus
      regimen, from the second treatment (day 14) onwards, selamectin achieved 83-100%
      reductions in R. sanguineus and D. variabilis counts 3 days after infestation,
      and 94-100% reductions 5 days after infestation in three of the four studies. In
      the fourth study, selamectin demonstrated good efficacy against D. variabilis for
      2 weeks after each treatment. In all seven studies, the counts from the
      selamectin-treated dogs were significantly (P< or =0.018) lower than those from
      the vehicle-treated dogs on 77 of the 80 assessments made 5 days after
      infestation. Selamectin also significantly (P< or =0.0105) reduced engorgement of
      female D. variabilis. These studies demonstrated that selamectin, administered
      topically to the skin in a single spot at a minimum dosage of 6mgkg(-1) at
      monthly intervals, was effective in the control of experimentally induced R.
      sanguineus and D. variabilis infestations on dogs.

PMID- 10940536
TI  - Safety of selamectin in dogs.
AB  - Selamectin is a broad-spectrum avermectin endectocide for treatment and control
      of canine parasites. The objective of these studies was to evaluate the clinical
      safety of selamectin for topical use in dogs 6 weeks of age and older, including
      breeding animals, avermectin-sensitive Collies, and heartworm-positive animals.
      The margin of safety was evaluated in Beagles, which were 6 weeks old at study
      initiation. Reproductive, heartworm-positive, and oral safety studies were
      conducted in mature Beagles. Safety in Collies was evaluated in avermectin
      sensitive, adult rough-coated Collies. Studies were designed to measure the
      safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body
      weight. Endpoints included clinical examinations, clinical pathology, gross and
      microscopic pathology, and reproductive indices. Selected variables in the margin
      of safety and reproductive safety studies were subjected to statistical analyses.
      Pups received large doses of selamectin at the beginning of the margin of safety
      study when they were 6 weeks of age and at their lowest body weight, yet
      displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin
      had no adverse effects on reproduction in adult male and female dogs. There were
      no adverse effects in avermectin-sensitive Collies or in heartworm-positive dogs.
      Oral administration of the topical formulation caused no adverse effects.
      Selamectin is safe for topical use on dogs at the recommended minimum dosage of
      6mgkg(-1) (6-12mgkg(-1)) monthly starting at 6 weeks of age, and including dogs
      of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs.

PMID- 10940538
TI  - Time course for the induction and maintenance of tolerance to Delta(9)
      tetrahydrocannabinol in mice.
AB  - The time course for the development of tolerance to delta-9-tetrahydrocannabinol
      (Delta(9)-THC) was studied in an effort to determine the role that length of
      dosing may have in the onset and maintenance of tolerance. Mice were chronically
      treated with either vehicle or 10 mg/kg of Delta(9)-THC subcutaneously twice a
      day. The mice were tested 24 h after the last injection for tolerance as assessed
      by the production of antinociception and suppression of spontaneous activity.
      Tolerance was first observed after three injections of Delta(9)-THC (1.5 days)
      resulting in a 7-fold and 23-fold decrease in potency for the measures of
      antinociception and hypoactivity, respectively. Seven injections of Delta(9)-THC
      (3.5 days of dosing) resulted in a 12-fold and 36-fold decrease in potency,
      respectively, while 13 injections of Delta(9)-THC (6.5 days of dosing) produced a
      6.2-fold and 9.8-fold degree of tolerance. The time course for the recovery from
      Delta(9)-THC-induced tolerance was also determined with a separate group of
      animals. Mice were dosed for 6.5 days with 10 mg/kg of Delta(9)-THC and were not
      tested until 4.5, 7.5, and 11.5 days after cessation of drug treatment. After 4.5
      days without drug treatment the mice exhibited a 7.5-fold and 2.3-fold degree of
      tolerance as measured by antinociception and hypoactivity, respectively. After 7.
      5 days without drug treatment a 3.4-fold degree of tolerance remained for the
      measure of antinociception, while no tolerance was detected for the measure of
      hypoactivity. No tolerance was observed for the measure of antinociception after
      11.5 days without drug treatment. This time course indicates that the mechanisms
      responsible for either the production or maintenance of tolerance differ between
      the measures of antinociception and suppression of spontaneous activity.

PMID- 10940537
TI  - Safety of selamectin in cats.
AB  - The safety of the avermectin, selamectin, was evaluated for topical use on the
      skin of cats of age six weeks and above, including reproducing cats and cats
      infected with adult heartworms. All studies used healthy cats. Acute safety was
      evaluated in domestic cross-bred cats. Margin of safety was evaluated in domestic
      shorthaired cats, starting at six weeks of age. Reproductive, heartworm-infected,
      and oral safety studies were conducted in adult, domestic-shorthaired cats.
      Studies were designed to measure the safety of selamectin at the recommended
      dosage range of 6-12mgkg(-1) of body weight. Assessments included clinical,
      biochemical, pathologic, and reproductive indices. Selected variables in the
      margin of safety study and the reproductive studies were subjected to statistical
      analyses by using a mixed linear model. Cats received large doses of selamectin
      at the beginning of the margin of safety study when they were six weeks of age
      and at their lowest body weight, yet displayed no clinical or pathologic evidence
      of toxicosis. Similarly, selamectin had no adverse effect on reproduction in
      adult male and female cats. There were no adverse effects in heartworm-infected
      cats. Oral administration of the topical formulation, which might occur
      accidentally, caused mild, intermittent, self-limiting salivation and vomiting.
      Selamectin is a broad-spectrum avermectin endectocide that is safe for use in
      cats starting at six weeks of age, including heartworm-infected cats and cats of
      reproducing age, when administered topically to the skin monthly at the
      recommended dosage to deliver at least 6mgkg(-1).

PMID- 10940539
TI  - Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5
      HT(1A)), dopamine (D(2)) and benzodiazepine receptors.
AB  - A large series of beta-carbolines was examined for their ability to bind at
      [3H]agonist-labeled 5-HT(2A) serotonin receptors. Selected beta-carbolines were
      also examined at 5-HT(2C) serotonin receptors, 5-HT(1A) serotonin receptors,
      dopamine D(2) receptors, and benzodiazepine receptors. Indolealkylamines and
      phenylisopropylamines were also evaluated in some of these binding assays. The
      beta-carbolines were found to bind with modest affinity at 5-HT(2A) receptors,
      and affinity was highly dependent upon the presence of ring substituents and ring
      saturation. The beta-carbolines displayed little to no affinity for 5-HT(1A)
      serotonin receptors, dopamine D(2) receptors and, with the exception of beta-CCM,
      for benzodiazepine receptors. Examples of beta-carbolines, indolealkylamines
      (i.e. N,N-dimethyltryptamine analogs), and phenylisopropylamines have been
      previously shown to produce common stimulus effects in animals trained to
      discriminate the phenylisopropylamine hallucinogen DOM (i.e. 1-(2, 5-dimethoxy-4
      methylphenyl)-2-aminopropane) from vehicle. Although the only common receptor
      population that might account for this action is 5-HT(2A), on the basis of a lack
      of enhanced affinity for agonist-labeled 5-HT(2A) receptors, as well as on their
      lack of agonist action in the PI hydrolysis assay, it is difficult to conclude
      that the beta-carbolines behave in a manner consistent with that of other
      classical hallucinogens.

PMID- 10940540
TI  - Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and
      CB(2) receptor binding.
AB  - The N-1 alkyl side chain of the aminoalkylindole analogues (AAI) has been
      implicated as one of a three-point interaction with the cannabinoid CB(1)
      receptor. In this study, the morpholinoethyl of WIN 55,212-2 was replaced with
      carbon chains of varying lengths ranging from a methyl to heptyl group.
      Additional groups were added to the naphthoyl and the C2 positions of the
      molecule. These structural changes revealed that high affinity binding to the
      CB(1) and CB(2) receptors requires an alkyl chain length of at least three
      carbons with optimum binding to both receptors occurring with a five carbon side
      chain. An alkyl chain of 3-6 carbons is sufficient for high affinity binding;
      however, extension of the chain to a heptyl group results in a dramatic decrease
      in binding at both receptors. The unique structure of the cannabimimetic indoles
      provides a useful tool to define the ligand-receptor interaction at both
      cannabinoid receptors and to refine proposed pharmacophore models.

PMID- 10940541
TI  - Heroin-related deaths in New South Wales, Australia, 1992-1996.
AB  - The coronial files of all heroin-related fatalities that occurred in New South
      Wales (NSW) over the period 1992-1996 were inspected. There were 953 heroin
      related fatalities in NSW over the study period. There was a substantial,
      statistically significant increase in heroin-related fatalities over the study
      period, from 152 deaths in 1992 to 226 during 1996. The mean age of cases was
      31.0 years, 85% were male, and 85% were classified as dependent on heroin at the
      time of death. There was a significant increase in the age of cases over the
      study period and the proportion of cases that were employed. Fatalities
      predominantly occurred in home settings (61%). No intervention occurred in 79% of
      cases. Fifty deaths (5%) occurred in the month following release from prison, 16
      of which occurred the first 24 hours after release. Morphine concentrations rose
      from 0.24 mg/l in 1992 to 0.38 mg/l in 1996. Seventy six percent of cases
      involved heroin in combination with other drugs: alcohol (46%), benzodiazepines
      (27%), antidepressants (7%) and cocaine (7%). In only 24% of cases was morphine
      the sole drug detected. Males were significantly more likely to have alcohol
      detected at autopsy (49 vs. 24%), while females were more likely to have
      benzodiazepines detected (41 vs. 17%). The median blood morphine concentration
      among cases in which alcohol was detected was significantly lower than other
      cases (0.27 vs. 0.39 mg/l). It is concluded that heroin-related deaths continued
      to rise throughout the study period, and that deaths were predominantly among
      older, untreated males. Despite the rise in blood morphine concentrations,
      polydrug use remained the predominant toxicological pattern.

PMID- 10940542
TI  - Chemical dependency treatment and employment outcomes: results from the 'ADATSA'
      program in Washington State.
AB  - The Alcohol and Drug Addiction Treatment and Support Act (ADATSA) created a
      treatment program for indigent clients in Washington State. This research
      assesses the relationship between the level of treatment services received and
      subsequent employment outcomes. Clients who completed their plan of treatment
      earned more than those who did not, controlling for other factors. Those clients
      who received vocational services, in addition to completing treatment, earned
      more than those who completed treatment only. While on average wages were low,
      this study does show that clients once deemed 'unemployable' can become
      productive.

PMID- 10940544
TI  - Self-help group attendance and participation among cocaine dependent patients.
AB  - The authors examined frequency and patterns of self-help group attendance and
      active participation over a 6-month period among 411 patients receiving treatment
      in the NIDA Collaborative Cocaine Treatment Study. Nearly two-thirds of patients
      attended at least one self-help group, and nearly all of these actively
      participated. Alcoholics Anonymous and Narcotics Anonymous meetings were attended
      most frequently. Statistical analyses included chi square, one-way analyses of
      variance, and cluster techniques. While patterns of attendance were relatively
      consistent over time, findings suggest that a treatment emphasizing the
      importance of self-help groups is likely to encourage more self-help group
      attendance and participation over time.

PMID- 10940543
TI  - A double-blind, placebo-controlled outpatient trial of pergolide for cocaine
      dependence.
AB  - Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine
      receptor agonist, may be useful in treating cocaine dependence. To empirically
      investigate this possibility, we conducted a 5-year, double-blind, placebo
      controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in
      subjects with cocaine dependence and combined cocaine/alcohol dependence. Data
      analysis was performed on an intent to treat population (N=358) and a per
      protocol population (N=108) with urine drug screens (UDS) used as the main
      outcome measure. There were no significant effects on UDS at either pergolide
      dose. Pergolide had no significant effect on alcohol use in the comorbid
      alcohol/cocaine dependence group. Pergolide does not appear to have clinical
      value in the treatment of cocaine dependence or in decreasing alcohol use in
      cocaine-dependent individuals at the presently studied doses.

PMID- 10940545
TI  - Analysis of risk taking in adults with a history of high risk behavior.
AB  - Antisocial behavior often involves frequent risk-taking, e.g. excessive substance
      use and criminality, which may lead to destructive consequences. In the present
      study, adults with a history of high-risk behavior (primarily drug dependence and
      conduct disorder) and matched controls worked on a novel laboratory task designed
      to measure risk-taking. The contingencies of the task were such that choosing a
      'risky' response option resulted in a net loss of monetary earnings compared to a
      safer, more conservative response alternative. The risky option offered a low
      probability of a large monetary reward or a high probability of a smaller
      monetary loss. The non-risky option protected current earnings. High-risk history
      subjects chose the risky option more often, had lower overall earnings, and were
      more likely to persist in making (losing) risky responses following a single gain
      on the risky option. The data support theories of maladaptive behavior focused on
      hypersensitivity to reward and insensitivity to aversive events.

PMID- 10940546
TI  - Cocaine dependence with and without comorbid depression: a comparison of patient
      characteristics.
AB  - This study compared depressed cocaine dependent patients (CD, N=50) with patients
      who were cocaine dependent only (CO, N=101) on pre-treatment psychiatric
      symptomatology, substance use, and psychosocial functioning. Results indicated
      that the CD group had more overall distress and poorer psychiatric functioning
      than the CO group. CD individuals scored higher on all subscales of the SCL-90-R,
      had a higher prevalence of antisocial personality disorder, reported higher
      craving for cocaine, lower self-efficacy to refrain from drug use, and lower
      perceived social support. These findings support the need for more intensive
      treatment approaches for dually-diagnosed patients.

PMID- 10940547
TI  - Bitter and sweet components of ethanol taste in humans.
AB  - This study examined taste descriptions elicited by ethanol and by other tastants
      in humans. All subjects described 10% ethanol as bitter and approximately 30% of
      the subjects described it as sweet and/or sour. Highly significant correlations
      were found between sweetness of some sucrose solutions (0.6-1%) and intensity of
      the taste of ethanol. In another experiment, quinine (bitter) solutions were
      rated as similar to 10% ethanol taste and this effect was potentiated by the
      addition of sucrose. In contrast, citric acid (sour) tended to decrease
      similarity ratings when added to the quinine solutions. Taken together, these
      findings suggest that: (1) in humans ethanol tastes both bitter and sweet; and
      (2) the relationship between sucrose and ethanol intakes previously found in
      animals and humans may result, at least partially, from similar taste responses
      elicited by sucrose and ethanol.

PMID- 10940548
TI  - Neural responses associated with cue evoked emotional states and heroin in opiate
      addicts.
AB  - Ten male opiate addicts, who were current heroin injectors, underwent positron
      emission tomographic (PET) scanning during exposure to a sequence of six
      alternating drug related and neutral video cues, on two occasions. After the
      second scan, each subject received heroin or placebo using a randomised single
      blind procedure. This design allowed the investigation of patterns of brain
      activity during a range of self-reported cue evoked emotional states, both in the
      presence and absence of heroin. Self-reports of 'urge to use' correlated strongly
      with increased regional blood flow (rCBF) in the inferior frontal and
      orbitofrontal cortex target regions of the mesolimbic dopaminergic system,
      implicated in conditioning and reward. 'Urge to use' was also associated with
      highly significant increased rCBF in the right pre-cuneus, an area associated
      with episodic memory retrieval, and in the left insula, implicated in the
      processing of the emotional components of stimuli. Self-reports of feeling 'high'
      correlated with rCBF activation in the hippocampus, an area relevant to the
      acquisition of stimulus-associated reinforcement.

PMID- 10940549
TI  - Chromatin organization and transcriptional control of gene expression in
      Drosophila.
AB  - It is increasingly clear that the packaging of DNA in nucleosome arrays serves
      not only to constrain the genome within the nucleus, but also to encode
      information concerning the activity state of the gene. Packaging limits the
      accessibility of many regulatory DNA sequence elements and is functionally
      significant in the control of transcription, replication, repair and
      recombination. Here, we review studies of the heat-shock genes, illustrating the
      formation of a specific nucleosome array at an activatable promoter, and describe
      present information on the roles of DNA-binding factors and energy-dependent
      chromatin remodeling machines in facilitating assembly of an appropriate
      structure. Epigenetic maintenance of the activity state within large domains
      appears to be a key mechanism in regulating homeotic genes during development;
      recent advances indicate that chromatin structural organization is a critical
      parameter. The ability to utilize genetic, biochemical and cytological approaches
      makes Drosophila an ideal organism for studies of the role of chromatin structure
      in the regulation of gene expression.

PMID- 10940550
TI  - MetaBlasts: tracing protein tyrosine phosphatase gene family roots from Man to
      Drosophila melanogaster and Caenorhabditis elegans genomes.
AB  - At increasing speed, sequencing data are being made public from both complex and
      simple life forms. Although biomedical interests tend to focus on mammalian
      genes, only simple organisms allow rapid genetic manipulation and functional
      analysis. A prerequisite for the meaningful extrapolation of gene functional
      studies from invertebrates to man is that the orthologs under study are
      unambiguously linked. However, identifying orthologs is not trivial, especially
      where large gene families are involved. We present here an automated sequence
      analysis procedure that allows a rapid visualization of most likely ortholog
      pairs. We illustrate the utility of this approach for the human gene family of
      protein tyrosine phosphatases (PTPs) as compared with the full set of
      Caenorhabditis elegans and Drosophila melanogaster conceptual ORFs. The approach
      is based on a reciprocal series of BLAST searches, which are automatically stored
      and represented in an HTML-formatted table. We have used this 'MetaBlast'
      approach to compile lists of human PTPs and their worm and fly orthologs. Many of
      these PTP orthologs had not been previously identified as such.

PMID- 10940551
TI  - Walking into the unknown: a 'step down' PCR-based technique leading to the direct
      sequence analysis of flanking genomic DNA.
AB  - We describe a novel and efficient PCR-based technique for walking into unknown
      flanking genomic DNA without recourse to protracted laborious library screening
      for overlapping sequences. This two component 'hot start' and 'step down' PCR
      method uses 6x1 microg of genomic DNA (ca 20kb in length) restricted with six
      different endonucleases and ligated to adaptors with the inclusion of two further
      restriction enzymes to prevent self-ligation. This allowed us to walk, in a
      single step, up to 6kb into flanking DNA and gave sufficient PCR products for up
      to 200 different walking experiments. This technology enabled us to clone and
      characterize the previously elusive 5' sequence of the barley powdery mildew
      chitin synthase gene, BgChs2, which includes a myosin motor-like sequence fused
      to a type V chitin synthase gene.

PMID- 10940552
TI  - Characterization and chromosomal mapping of a novel human gene, ANKHZN.
AB  - Ankhzn (ankyrin repeats hooked to a zinc finger motif) was originally isolated by
      means of the gene trap method, as a novel cytoplasmic protein on mouse embryonic
      stem cells. The Ankhzn protein is ubiquitously expressed in a spatiotemporal
      specific manner and is located on endosomes. In the present study, we have cloned
      human ANKHZN cDNA by PCR using candidate EST clones exhibiting a high homology to
      mouse Ankhzn cDNA. The human ANKHZN cDNA encoded a 1166aa protein exhibiting
      84.9% identity to the mouse one. The size of the transcript was found to be about
      7kb on a Northern blot analysis, and ANKHZN mRNA was found to be ubiquitously
      expressed in human tissues on RT-PCR analysis. Western blot analysis showed that
      a 130kDa protein was detected at various levels in human tissues and also present
      in both membrane and soluble fractions obtained on subcellular fractionation.
      Human ANKHZN is a single copy gene consisting of predicted 25 exons in the human
      genome, and has been mapped to human chromosome 17p13 by radiation hybrid panel
      and fluorescence in-situ hybridization.

PMID- 10940553
TI  - The human per1 gene: genomic organization and promoter analysis of the first
      human orthologue of the Drosophila period gene.
AB  - Per genes encode components of the circadian clocks controlling metabolic and
      behavioural rhythms. The human Per1 cDNA, RIGUI, was previously isolated and
      mapped on chromosome 17p12 (Sun, Z.S., Albrecht, U., Zhuchenko, O., Bailey, J.,
      Eichele, G., Lee, C.C., 1997. RIGUI, a putative mammalian orthologue of the
      Drosophila period gene. Cell 90, 1003-1011). We have now isolated the entire
      genomic locus containing the human Per1 gene, in a search for genes associated
      with CpG-rich sequences. The hPer1 gene spans 15kb of human genomic DNA and is
      composed of 23 exons, flanked by 5' and 3' regulatory regions. Comparison of the
      hPer1 genomic clone with the dbEST database revealed homologies with putative
      alternative transcripts. Functional mapping within the 5' CpG-rich regulatory
      region enabled us to locate the hPer1 promoter core in a 510bp-long sequence
      centred around a TATA box, which supports high levels of hPer1 transcription. A
      second regulatory region was formally identified in intron 1, which appears to
      exert a negative role in transcriptional control of hPer1. These regions may be
      differentially involved in tissue-specificity, and/or circadian regulation, of
      the human hPer1 gene transcription.

PMID- 10940554
TI  - Genomic organization and chromosome localization of the newly identified human
      heparanase gene.
AB  - Heparanase (HPSE), which we have recently isolated, is an endo-beta-D
      glucuronidase capable of cleaving heparan sulfate and has been implicated in
      inflammation and tumor angiogenesis and metastasis. In this report, the genomic
      organization and chromosome localization of the human heparanase gene is
      described. Polymerase chain reaction, subcloning and DNA sequencing analysis of a
      bacterial artificial chromosome (BAC) clone revealed that the 3.7 kb human
      heparanase cDNA is spread over about 50 kb and contains 14 exons and 13 introns.
      The heparanase gene is expressed as two mRNA species containing the same open
      reading frame, HPSE 1a (5 kb) (GenBank Data Library under accession number:
      AF155510); and HPSE 1b (1.7 kb) (GenBank Data Library under accession number:
      AF144325), generated by alternative splicing. The HPSE 1a-form contains all 14
      exons, whereas in the HPSE 1b-form the first and fourteenth exons (5'- and 3'
      untranslated region) have been spliced out. All splice sites conform to the GT-AG
      rule, except for the splice donor site of intron 13 (which is GA instead of GT),
      and the splice acceptor of intron 13 (which is GG instead of AG). Fluorescence in
      situ hybridization and radiation hybrid mapping suggest that the heparanase gene
      is located on human chromosome 4q22. This report regarding the structure of the
      human heparanase gene will aid in understanding the genetic contribution of this
      gene to normal physiology as well as to disease states. A possible involvement of
      heparanase in neuronal degeneration is discussed.

PMID- 10940555
TI  - Disruption of the microsomal glutathione S-transferase-like gene reduces life
      span of Drosophila melanogaster.
AB  - Microsomal glutathione S-transferase-I (MGST-I) has been thought to be important
      for protecting the cell from oxidative damages and/or xenobiotics. We have
      previously identified the Microsomal glutathione S-transferase-like (Mgstl) gene,
      a Drosophila homologue of human MGST-I. To investigate the function of the enzyme
      using Drosophila as a model system, we examined the expression pattern of Mgstl
      during development, and generated loss-of-function mutants to assess its in-vivo
      function. Mgstl was expressed in all developmental stages. It is expressed
      ubiquitously with the highest expression in the larval fat body, an insect organ
      thought to be functionally corresponding to mammalian liver, while relatively low
      in the central nervous system. This tissue distribution is consistent with that
      of MGST-I in humans or Rats. Mgstl null mutants generated from a P element
      insertion line showed no obvious defects in morphology, indicating that it is not
      essential for the development. However, their life span was significantly reduced
      compared to control flies, suggesting that the MGSTL protein is involved in
      processes somehow contributing to aging. We found an Mgstl pseudogene, which is
      apparently derived through the reverse transcription of Mgstl mRNA and subsequent
      integration into the genome.

PMID- 10940556
TI  - Identification and molecular analysis of BANP.
AB  - BTG3 belongs to a family of structurally related genes whose biochemical
      functions remain elusive. In order to investigate the mechanism underlying BTG3
      mediated functions, we tried to identify BTG3 potential partners. The use of the
      yeast 'two-hybrid system', with BTG3 as bait, enabled us to isolate BANP (BTG3
      Associated Nuclear Protein). Other commonly used protein-binding assays did not
      confirm this yeast interaction. However, BANP had never been described before,
      and this prompted us to further characterise this gene. In this paper, we present
      data on its molecular organization in mouse, then we speculate on the nature of
      this nuclear protein, and finally we localise BANP on the human chromosome 16q24
      subregion; we discuss the fact that frequent loss of heterozygosity within this
      region has been observed in different tumours.

PMID- 10940557
TI  - Clustering of mandibular organ-inhibiting hormone and moult-inhibiting hormone
      genes in the crab, Cancer pagurus, and implications for regulation of expression.
AB  - Development and reproduction of crustaceans is regulated by a combination of
      neuropeptide hormones, ecdysteroids (moulting hormones) and the isoprenoid,
      methyl farnesoate (MF), the unepoxidised analogue of insect juvenile hormone-III
      (JH-III). MF and the ecdysteroids are respectively synthesised under the negative
      control of the sinus gland-derived mandibular organ-inhibiting hormones (MO-IHs)
      and moult-inhibiting hormone (MIH) that are produced in eyestalk neural ganglia.
      Previous work has demonstrated the existence of two isoforms of MO-IH, called MO
      IH-1 and -2, that differ by a single amino acid in the mature peptide and one in
      the putative signal peptide. To study the structural organisation of the crab MIH
      and MO-IH genes, a genomic DNA library was constructed from DNA of an individual
      female crab and screened with both MO-IH and MIH probes. The results from genomic
      Southern blot analysis and library screening indicated that the Cancer pagurus
      genome contains at least two copies of the MIH gene and three copies of the MO-IH
      genes. Upon screening, two types of overlapping genomic clone were isolated. Each
      member of one type of genomic clone contains a single copy of each of the
      convergently transcribed MO-IH-1 and MIH genes clustered within 6.5kb. The other
      type contains only the MO-IH-2 gene, which is not closely linked to an MIH gene.
      There are three exons and two introns in all MIH and MO-IH genes analysed. The
      exon-intron boundary of the crab MIH and MO-IH genes follows Chambon's rule (GT
      AG) for the splice donor and acceptor sites. The first intron occurs within the
      signal peptide region and the second intron occurs in the coding region of the
      mature peptide. Sequence analysis of upstream regions of MO-IH and MIH genes
      showed that they contained promoter elements with characteristics similar to
      other eukaryotic genes. These included sequences with high degrees of similarity
      to the arthropod initiator, TATA box and cAMP response element binding protein.
      Additionally, putative CF1/USP and Broad Complex Z2 transcription factor elements
      were found in the upstream regions of MIH and MO-IH genes respectively. The
      implications of the presence of the latter two putative transcription factor
      binding-elements for control of expression of MIH and MO-IH genes is discussed.
      Phylogenetic analysis and gene organisation show that MO-IH and MIH genes are
      closely related. Their relationship suggests that they represent an example of
      evolutionary divergence of crustacean hormones.

PMID- 10940558
TI  - The insulator protein CTCF represses transcription on binding to the
      (gt)(22)(ga)(15) microsatellite in intron 2 of the HLA-DRB1(*)0401 gene.
AB  - The insulator and transcription factor CTCF is a highly conserved 11 zinc finger
      protein possessing multiple specifities in DNA sequence recognition. CTCF
      regulates transcription of several genes, like the human oncogene c-myc or the
      chicken lysozyme gene by binding extremely divergent DNA sequences with different
      sets of its 11 zinc fingers. Recently, an insulator function was demonstrated for
      several CTCF binding elements. Here we show that CTCF binds to the
      (gt)(22)(ga)(15) microsatellite repeat A9 in intron 2 of the HLA-DRB1(*)0401
      gene. Reporter gene activity is repressed by the A9 element. This repression is
      dependent on coexpressed CTCF and is even stronger compared with the CTCF binding
      site F1 of the chicken lysozyme gene, for which a silencer activity has been
      shown. This is the first report suggesting a function for microsatellite
      sequences in regulating specific gene expression.

PMID- 10940559
TI  - Cloning and characterization of the mouse tob2 gene.
AB  - Human Tob2 is a member of the Tob/BTG1 anti-proliferative family of proteins.
      Here, we report the molecular cloning and characterization of the mouse tob2
      gene. The tob2 gene contains an open reading frame of 345 amino acids with an 89%
      identity to its human counterparts. The coding region of mouse tob2 is not
      interrupted by introns. The tob2 transcript is 4.2kb long, the size being similar
      to that of the human tob2 transcript, and detected ubiquitously in various
      tissues of adult mice. In addition, in situ hybridization shows that tob2 is
      ubiquitously expressed in embryo, the level of expression being especially high
      in skeletal muscle. Collectively, Tob2 is suggested to play roles both during
      embryogenesis and in adults.

PMID- 10940560
TI  - Genetic engineering of Escherichia coli to produce a 1:1 complex of the anabaena
      sp. PCC 7120 nuclease NucA and its inhibitor NuiA.
AB  - A series of T7-promoter based bicistronic expression vectors was constructed in
      order to produce the complex of the Anabaena sp. PCC 7120 DNA/RNA non-specific
      nuclease NucA and its inhibitor NuiA. With all constructs, tandem expression of
      nucA and nuiA results in aggregation and inclusion body formation of NucA,
      independent of the order of the genes, the relative expression of the two
      proteins and the temperature applied during expression. Two constructs in which
      nuiA is the first and nucA the second cistron lead to an approximately one order
      of magnitude higher expression of nuiA compared with nucA. In these cells
      inclusion bodies are formed which contain NucA and NuiA in a 1:1 molar ratio. The
      complex can be solubilized with 6M urea after disruption of the cells by
      sonication, renatured by dialysis and purified to homogeneity. 2mg of the complex
      are obtained from 1l Escherichia coli culture. As shown by gel filtration and
      analytical ultracentrifugation, our system leads to a highly pure and homogeneous
      complex preparation, as required for biophysical and structural studies. Thus,
      our new method is a superior alternative for the production of the NucA/NuiA
      complex in which separately produced nuclease and inhibitor are mixed, and an
      excess of one or the other component, as well as aggregates of NucA, have to be
      removed from the preparation.

PMID- 10940561
TI  - Correlation of the exon/intron organization to the conserved domains of the mouse
      transcriptional corepressor TIF1beta.
AB  - TIF1beta, a member of the transcriptional intermediary factor 1 family, has been
      reported to function as a corepressor for the large class of KRAB domain
      containing zinc finger proteins of the Kruppel type. In this study, we report the
      genomic organization and nucleotide sequence of the mouse TIF1beta gene. This
      gene comprises 17 coding exons located within 7 kb of genomic DNA. Exon sizes
      vary from 37 bp (exon 10) to 901 bp (exon 1), and intron sizes range from 71 bp
      to 1843 bp. All introns have the conserved GT and AG dinucleotides present at the
      donor and acceptor sites, respectively. The functional/homology regions of the
      TIF1beta protein are encoded by distinct exons. The amino-terminal RING finger is
      encoded by two exons interrupted by a small intron. The B boxes lie within
      individual exons. Similarly to the RING finger, the PHD finger is encoded by two
      exons. Three exons constitute the carboxy-terminal bromodomain, and their
      position correlates well with the secondary structure elements of the domain as
      predicted by computer modeling. Taken together, these results will facilitate the
      genetic manipulation of TIF1beta for future in vivo structure-function studies.

PMID- 10940562
TI  - Genomic and functional characterization of the oas gene family encoding O
      acetylserine (thiol) lyases, enzymes catalyzing the final step in cysteine
      biosynthesis in Arabidopsis thaliana.
AB  - The final step of cysteine biosynthesis in plants is catalyzed by O-acetylserine
      (thiol) lyase (OAS-TL), which occurs as several isoforms found in the cytosol,
      the plastids and the mitochondria. Genomic DNA blot hybridization and isolation
      of genomic clones indicate single copy genes (oasA1, oasA2, oasB and oasC) that
      encode the activities of OAS-TL A, B and C found in separate subcellular
      compartments in the model plant Arabidopsis thaliana. Sequence analysis reveals
      that the newly discovered oasA2 gene represents a pseudogene that is still
      transcribed, but is not functionally translated. The comparison of gene
      structures suggests that oasA1/oasA2 and oasB/oasC are closely related and may be
      derived from a common ancestor by subsequent duplications. OAS-TL A, B and C were
      overexpressed in an Escherichia coli mutant lacking cysteine synthesis and
      exhibited bifunctional OAS-TL and beta-cyanoalanine synthase (CAS) activities.
      However, all three proteins represent true OAS-TLs according to kinetic analysis
      and are unlikely to function in cyanide detoxification or secondary metabolism.
      In addition, it was demonstrated that the mitochondrial OAS-TL C exhibits in vivo
      protein-protein interaction capabilities with respect to cysteine synthase
      complex formation similar to cytosolic OAS-TL A and plastid OAS-TL B. Multiple
      database accessions for each of the A. thaliana OAS-TL isoforms can thus be
      attributed to a specified number of oas genes to which functionally defined gene
      products are assigned, and which are responsible for compartment-specific
      cysteine synthesis.

PMID- 10940563
TI  - Mutation detection by pyrosequencing: sequencing of exons 5-8 of the p53 tumor
      suppressor gene.
AB  - The ability to sequence a large number of DNA samples rapidly and accurately for
      detection of all possible mutations is a critical goal for the future application
      of DNA sequencing in routine medical diagnostics. Pyrosequencing() is a non
      electrophoretic real-time DNA sequencing method that uses the luciferase
      luciferin light release as the detection signal for nucleotide incorporation into
      target DNA. For pyrosequencing of the human p53 gene, a nested multiplex PCR
      method for amplification of exons 5-8 was prepared. In order to investigate the
      use of pyrosequencing in mutation detection, DNA samples from skin-cancer
      patients were used. Two forms of nucleotide dispensation strategy were used,
      cyclic and programmed. Bi-directional pyrosequencing was performed and the
      overlapping sequence data produced were assembled to determine the sequence of
      the gene. Reliable sequencing data were obtained with both dispensation
      strategies, but some advantages were obtained using the programmed nucleotide
      dispensation approach, such as longer and faster reads, and fewer out-of-phase
      problems. The accuracy of pyrosequencing for detection of p53 mutations and
      allele distribution was demonstrated.

PMID- 10940564
TI  - Molecular characterization of the gyrB region of the oral spirochete, Treponema
      denticola.
AB  - The nucleotide (nt) sequence of the Treponema denticola (Td) DNA gyrase beta
      subunit gene (gyrB) has been determined. Southern blot analysis of Td chromosomal
      DNA indicated that gyrB is present as a single copy. Approximately 3.2kb of the
      nt sequence 5' and 0.7kb of nucleotide sequence 3' of gyrB were obtained.
      Analysis of the deduced amino acid (aa) sequence revealed two complete open
      reading frames (ORFs) (ORF1 and ORF3) and a truncated ORF (ORF4'). ORF1 has no
      homology to sequences in the databases, whereas ORF3 and ORF4' have significant
      homology to several bacterial DnaA (replication initiator) and DnaE (DNA
      polymerase III) proteins respectively. RT-PCR data showed that orf1-gyrB are co
      transcribed, while dnaA-dnaE are co-transcribed but in the opposite direction.
      These data indicated that the gene organization of the Td gyrB region is unique
      compared with that of other bacteria. Eighteen putative DnaA boxes with several
      AT-rich regions were identified in the dnaA-dnaE intergenic region, and three
      putative DnaA boxes were identified in the gyrB-dnaA intergenic region.
      Spontaneous coumermycin A(1)-resistant Td mutants were isolated and
      characterized. The mutants have a >20-fold higher resistance to coumermycin A(1)
      than wild-type Td. A single point mutation in gyrB that changed GyrB Lys(136) to
      Glu or Thr appears to be responsible for the coumermycin A(1) resistance.

PMID- 10940565
TI  - Identification and molecular characterization of two novel Trypanosoma cruzi
      genes encoding polypeptides sharing sequence motifs found in proteins involved in
      RNA editing reactions.
AB  - We have previously identified a Trypanosoma cruzi cDNA encoding a protein named
      Tc52 sharing structural and functional properties with the thioredoxin and
      glutaredoxin protein family involved in thiol-disulphide redox reactions.
      Furthermore, we reported that Tc52 also plays a role in T. cruzi-associated
      immunosuppression observed during Chagas' disease. Moreover, Tc52 gene targeting
      deletion strategy allowed us to demonstrate that monoallelic disruption of Tc52
      resulted in the alteration of the metacyclogenesis process and the production of
      less virulent parasites. Sequence analysis of a 7358 bp genomic fragment
      containing the Tc52 encoding gene revealed two additional open reading frames
      (ORF-A and C). The ORFs are likely to have protein coding function by a number of
      criteria, including reverse transcriptase polymerase chain reaction (RT-PCR),
      Western blot and immunofluorescence analyses. The deduced amino-acid (aa)
      sequence of the ORF-A localized upstream of the Tc52 gene revealed that it
      contains within its N-terminus (aa 1 to 170) four RGG boxes known to act as RNA
      binding motifs in some proteins that interact with RNA, interspersed with a high
      density of glycine with regular spacing of tryptophan (WX(9-10)) in which X is
      often a glycine. Moreover, the C-terminal part of the ORF-C (aa 253-289) contains
      a motif that is strikingly similar (7-35% identity, 14-46% similarity over 28aa)
      to a short sequence (RNP1) comprising the consensus sequence RNA binding domain
      (CS-RBD) found in a number of proteins that interact with RNA. The aa sequence
      from the ORF-C localized downstream of the Tc52 gene showed significant homology
      to human adenosine deaminase acting on RNA (hADAT1) that specifically deaminates
      adenosine 37 to inosine in eukaryotic tRNA(Ala) and to its homologue yeast
      protein (Tad1p) (22-25% identity and an additional 38-40% similarity over 177aa).
      Moreover, highly similar motifs of the deaminase domain are present in the T.
      cruzi ORF-C. Furthermore, the 5' flanking regions of the genes contained repeat
      TATA and CAAT nucleotide sequences which resemble the motifs found upstream of
      the transcription initiation sites in eukaryotic promoters. Therefore, the
      characterization of novel T. cruzi genes encoding proteins which show similarity
      to components of RNA processing reactions provides new tools to investigate the
      gene expression regulation in these parasitic organisms. Moreover, our recent
      findings on the Tc52 encoding gene underline the interest of genetic manipulation
      of T. cruzi, not only making it possible to use more closely an in vitro approach
      to find out how genes function, but also to obtain 'attenuated' strains that
      could be used in the development of vaccinal strategies.

PMID- 10940566
TI  - Mycobacterium tuberculosis H37Rv comparative gene-expression analysis in
      synthetic medium and human macrophage.
AB  - Mycobacteria are intracellular pathogens that survive and grow in host
      macrophages. Following phagocytosis, sustained intracellular bacterial growth
      depends on its ability to avoid destruction by macrophage-mediated host defences
      such as lysosomal enzymes, reactive oxygen and the reactive nitrogen
      intermediates. This suggests that the interaction between host cell and microbe
      is delicately balanced, and can be tipped in favour of either organism. The
      identification of Mycobacterium tuberculosis H37Rv (MTB) genes expressed within
      host cells would contribute greatly to the development of new strategies to fight
      tuberculosis. In the present study, we compared MTB gene expression in the course
      of intra- (human macrophages) and extracellular growth (Sauton's medium) to
      ascertain whether differences might occur between gene-expression patterns in the
      two habitats of replication. Using reverse-transcriptase polymerase chain
      reaction (RT-PCR) on a group of 14 MTB-Complex-specific genes, we found that
      MT10Sa (a small stable RNA), 35 kDa (unknown), ahpC (alkyl hydroperoxide
      reductase, AhpC), sigF (alternative RNA Polymerase sigma factor), and katG
      (catalase-peroxidase, HPI) genes are expressed in both the environments, while
      Ag85B, Ag85C (members of the Antigen 85 Complex), rpoV (RNA Polymerase sigma
      factor) and ESAT6 (early secretory antigen, 6 kDa) are expressed only in the in
      vitro culture; on the other hand, Ag85A (Antigen 85 Complex), rpoB (RNA
      Polymerase beta sub-unit), pab (Protein antigen b), invA and invB genes (encoding
      proteins that show homologies with p60 of Listeria monocytogenes) are expressed
      only inside the macrophage. Positive RT-PCR products on cDNAs for these genomic
      regions were not obtained from approximately 1000-fold more bacteria grown in
      Laboratory Broth. Identification of M. tuberculosis genes expressed in response
      to phagocytosis by human macrophages increases our basic understanding of the
      host-pathogen interaction, and helps to identify bacterial factors necessary for
      in vivo survival and growth.

PMID- 10940567
TI  - Molecular integrity and usefulness of episomal expression vectors derived from BK
      and Epstein-Barr virus.
AB  - High-level and stable production of a protein of interest is one of the most
      important parameters when considering the development of an efficient vector
      system for heterologous gene expression. In order to achieve this goal, we have
      used episomal vector elements derived from Epstein-Barr virus (EBV) or BK virus
      (BKV) in combination with the strictly regulated interferon-inducible Mx
      promoter. Here we demonstrate that EBV-derived vectors replicate efficiently in
      all cell lines tested (i.e. HEK293, HeLaH21 and Vero), yielding stable
      transfectants with a high, inducible expression level and almost no background.
      In contrast, BKV-derived vectors are much more restricted to particular cell
      types and hampered by DNA rearrangements, which is a serious drawback for use
      over a longer timespan.

PMID- 10940568
TI  - Cotranscription of 5S rRNA-tRNA(Arg)(ACG) from Brassica napus chloroplasts and
      processing of their intergenic spacer.
AB  - S1 mapping showed that at least a significant portion of the 5S rRNA and
      tRNA(Arg)(ACG) is co-transcribed in canola chloroplast, making trnR the last gene
      transcribed in an operon of which the final sequence is 5'-16S-tRNA(Ile)
      tRNA(Ala)-23S-4.5S-5S-tRNA(Arg)-3'. Various RNA termini representing RNA
      processing sites at several parts of the 5S rRNA-tRNA(Arg) area were detected.
      This gene spacer is substantially conserved among various species compared here,
      and a secondary structure model for this chloroplast region in canola applies to
      other plant sequences. The conservation of this intergenic sequence suggests a
      functional role, possibly by providing recognition structures for endogenous
      RNases involved in its maturing process.

PMID- 10940569
TI  - The molecular evolution of signal peptides.
AB  - Signal peptides direct mature peptides to their appropriate cellular location,
      after which they are cleaved off. Very many random alternatives can serve the
      same function. Of all coding sequences, therefore, signal peptides might come
      closest to being neutrally evolving. Here we consider this issue by examining the
      molecular evolution of 76 mouse-rat orthologues, each with defined signal
      peptides. Although they do evolve rapidly, they evolve about half as fast as
      neutral sequences. This indicates that a substantial proportion of mutations must
      be under stabilizing selection. A few putative signal sequences lack a
      hydrophobic core and these tend to be more slowly evolving than others,
      indicating even stronger stabilizing selection. However, closer scrutiny suggests
      that some of these represent mis-annotations in GenBank. It is also likely that
      some of the substitutions are not neutral. We find, for example, that the rate of
      protein evolution correlates with that of the mature peptide. This may be a
      result of compensatory evolution. We also find that signal peptides of immune
      genes tend to be faster evolving than the average, which suggests an association
      with antagonistic co-evolution. Previous reports also indicated that the signal
      peptide of the imprinted gene, Igf2r, is also unusually fast evolving. This, it
      was hypothesized, might also be indicative of antagonistic co-evolution.
      Comparison of Igf2r's signal peptide evolution shows that, although it is not an
      outlier, its rate of evolution is comparable to that of many of the faster
      evolving immune system signal sequences and 5/6 of the amino acid changes do not
      conserve hydrophobicity. This is at least suggestive that there is something
      unusual about Igf2r's signal sequence.

PMID- 10940570
TI  - Identification and characterization of the gltK gene encoding a membrane
      associated glucose transport protein of pseudomonas aeruginosa.
AB  - The Pseudomonas aeruginosa oprB gene encodes the carbohydrate-selective OprB
      porin, which translocates substrate molecules across the outer membrane to the
      periplasmic glucose-binding protein. We identified and cloned two open reading
      frames (ORFs) flanking the oprB gene but are not in operonic arrangement with the
      oprB gene. The downstream ORF encodes a putative polypeptide homologous to
      members of a family of transcriptional repressors, whereas the oprB gene is
      preceded by an ORF encoding a putative product, which exhibits strong homology to
      several carbohydrate transport ATP-binding cassette (ABC) proteins. The genomic
      copy of the upstream ORF was mutagenized by homologous recombination. Analysis of
      the deletion mutant in comparison with the wild type revealed a significant
      reduction in [14C] glucose transport activity in the mutant strain, suggesting
      that this ORF likely encodes the inner membrane component of the glucose ABC
      transporter. It is thus designated gltK gene to reflect its homology to the
      Pseudomona fluorescens mtlK and its involvement in the high-affinity glucose
      transport system. Multiple alignment analysis revealed that the P. aeruginosa
      gltK gene product is a member of the MalK subfamily of ABC proteins.

PMID- 10940571
TI  - Nardostachys jatamansi protects against liver damage induced by thioacetamide in
      rats.
AB  - Nardostachys jatamansi is a medically important herb of Indian origin used for
      centuries in Ayurvedic and Unani systems of medicine for the treatment of various
      ailments. In the present paper, a 50% ethanolic extract of the rhizomes of N.
      jatamansi is shown to possess hepatoprotective activity. Pretreatment of rats
      with the extract (800 mg/kg body wt, orally) for three consecutive days
      significantly ameliorated the liver damage in rats exposed to the hepatotoxic
      compound thioacetamide. Elevated levels of serum transaminases
      (aminotransferases) and alkaline phosphatase, observed in thioacetamide alone
      treated group of animals, were significantly lowered in N. jatamansi pretreated
      rats. Pretreatment of the animals with the extract also resulted in an increase
      in survival in rats intoxicated with LD90 dose of the hepatotoxic drug.

PMID- 10940572
TI  - The efficiency of random versus ethno-directed research in the evaluation of
      Sinai medicinal plants for bioactive compounds.
AB  - Hexane, ethyl acetate and ethanol extracts of sixty plant species (growing wild
      in Sinai, Egypt) were screened for antibacterial and antifungal activities
      against a range of Gram-positive and Gram-negative bacteria, a yeast and
      dermatophytic fungi. Plants were collected either by random or ethno-directed
      methods. Plants collected at random (36 species) were gathered from different
      districts of Sinai, while the ethnobotanical collection (24 species) comprised
      species used in the folk medicine of the Bedouins in Sinai. Results indicate that
      plant sampling based on ethnobotanical approach produced greater number of plants
      showing antimicrobial activity. The results are discussed with respect to the
      ethnobotanical correlation of active species.

PMID- 10940573
TI  - Anti-microbial activity of a new vaginal contraceptive NIM-76 from neem oil
      (Azadirachta indica).
AB  - Efficacy of NIM-76, a spermicidal fraction from neem oil, was investigated for
      its antimicrobial action against certain bacteria, fungi and Polio virus as
      compared to whole neem oil. The NIM-76 preparation showed stronger anti-microbial
      activity than the whole neem oil. It inhibited growth of various pathogens tested
      including Escherichia coli and Kleibsiella pneumoniae which were not affected by
      the whole neem oil. NIM-76 also exhibited antifungal activity against Candida
      albicans and antiviral activity against Polio virus replication in vero cell
      lines. It also protected mice from systemic candidiasis as revealed by enhanced %
      survival and reduced colony forming units of C. albicans in various tissues. This
      shows that NIM-76 has a potent broad spectrum anti-microbial activity.

PMID- 10940574
TI  - Protection from phenytoin-induced cognitive deficit by Bacopa monniera, a reputed
      Indian nootropic plant.
AB  - Many epileptic patients suffer from cognitive impairments; both the underlying
      pathology and antiepileptic drug therapy can cause such deficits. Phenytoin, one
      of the widely used anticonvulsants, is known to adversely affect cognitive
      function. A reputed Indian nootropic plant Bacopa monniera (BM) was evaluated
      alone and in combination with phenytoin for its effect on (a) passive-avoidance
      (PA) task; (b) maximal electroshock seizures; and (c) locomotor activity in mice.
      Phenytoin (PHT, 25 mg/kg po x 14 days) adversely affected cognitive function in
      the PA task. BM extract (40 mg/kg x 7 days), given along with phenytoin in the
      second week of the two-week regimen, significantly reversed PHT-induced
      impairment. Both acquisition and retention of memory showed improvement without
      affecting its anticonvulsant activity. The observed cognitive effects of PHT and
      BM were found to be independent of motor stimulation. The results provide
      evidence for potential corrective effect of BM in cognitive deficit associated
      with PHT therapy.

PMID- 10940575
TI  - Hypoglycemic effects of lactucin-8-O-methylacrylate of Parmentiera edulis fruit.
AB  - Hypoglycemic activity-guided fractionation together with chemical analysis led to
      the isolation of one guaianolide (lactucin-8-O-methylacrylate) from the
      chloroform extract of the dried fruits of Parmentiera edulis. Identification was
      based on spectroscopic methods. The compounds lowers blood sugar levels after
      administration to alloxan-diabetic mice.

PMID- 10940576
TI  - Anti-inflammatory activity of Agave intermixta Trel. and Cissus sicyoides L.,
      species used in the Caribbean traditional medicine.
AB  - Agave intermixta Trel. and Cissus sicyoides L. are two tropical plants
      originating from the Dominican Republic. Aqueous extracts from these species are
      used in traditional medicine. In contrast, biological activity and toxicity of
      these plants are not yet evaluated systematically. The aim of the present work is
      to investigate a potential anti-inflammatory activity, and to elucidate the
      toxicity of the extracts. No lethal effects were produced after oral
      administration of the extracts. The values of the medium lethal doses after
      intraperitoneal administration were quite high for both species, although A.
      intermixta seems to be rather more toxic than C. sicyoides. The anti-inflammatory
      effects have been investigated in two experimental in vivo models. The
      carrageenan-induced rat paw oedema was chosen as a model for general
      inflammation, and the mice ear oedema test using tetradecanoylphorbol acetate as
      inflammatory agent as a model of topical inflammation. Dry extracts from
      decoctions of A. intermixta leaves and C. sicyoides stems were administered in
      doses of 300 and 500 mg/kg (p.o.) in the general model, and in doses of 3 and 5
      mg/mouse ear for both plants in the topical model. In the general anti
      inflammation assay, the oral administration of both extracts produced a
      significant anti-inflammatory effect, most pronounced for A. intermixta than for
      C. sicyoides. In the topical model, the administration of both extracts produced
      similar inhibitions of the oedema, with a reduction of approximately 50% in
      comparison with the control group. In homogenated tissue samples from the
      inflamed areas, a distinct decrease in the level of myeloperoxidase enzyme was
      noted.

PMID- 10940577
TI  - Distribution, metabolism and excretion of butylidenephthalide of Ligustici
      chuanxiong rhizoma in hairless mouse after dermal application.
AB  - The absorption, distribution and excretion of butylidenephthalide after dermal
      application to hairless mouse have been examined with [8-14C]butylidenephthalide.
      By the investigation of the whole body autoradiogram and liquid scintillation
      analysis, it was indicated that the transdermally applied butylidenephthalide
      quickly permeate into peripheral circulation system without accumulation in the
      skin and then distribute into lung, liver, bile and kidney. The total
      radioactivity, however, was decreased due to excretion into urine, and in the
      case of i.v.-administration, 80% of the administered butylidenephthalide was
      excreted into urine within 24 h, while only 5% was excreted into feces within 24
      h. Then, the metabolite in urine was determined to be a cysteine conjugate by
      liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.
      Thus, it has been concluded that after dermal application butylidenephthalide
      quickly permeates through skin into peripheral circulation system; distributes to
      lung, liver, bile and kidney; and then excreted into urine as a cysteine adduct.

PMID- 10940578
TI  - Contribution to the ethnobotanical, phytochemical and pharmacological studies of
      traditionally used medicinal plants in the treatment of dysentery and diarrhoea
      in Lomela area, Democratic Republic of Congo (DRC).
AB  - In order to collect ethnobotanical information about antidiarrhoeal plants, we
      performed inquiries among traditional healers, community leaders, and native
      people of Lomela villages in Congo. Six medicinal plants widely used in this
      region were designated as having antidysenteric and antidiarrhoeal properties.
      These six medicinal plants were screened for groups of phytochemical compounds
      with antibacterial and antiamoebic activities. They were found to contain
      tannins, alkaloids, saponins, flavonoids, sterols and/or triterpenes and reducing
      sugars. Of the six tested plants, three showed prominent antibacterial activity
      whereas two acted against Entamoeba histolytica. The usefulness of the
      phytochemical bases and biological activities of these plants as potential source
      of antidiarrhoeal remedies is discussed.

PMID- 10940579
TI  - Antioxidant properties of Asparagus racemosus against damage induced by gamma
      radiation in rat liver mitochondria.
AB  - The possible antioxidant effects of crude extract and a purified aqueous fraction
      of Asparagus racemosus against membrane damage induced by the free radicals
      generated during gamma-radiation were examined in rat liver mitochondria. gamma
      Radiation, in the dose range of 75-900 Gy, induced lipid peroxidation as assessed
      by the formation of thiobarbituric acid reactive substances (TBARS) and lipid
      hydroperoxides (LOOH). Using an effective dose of 450 Gy, antioxidant effects of
      A. racemosus extract were studied against oxidative damage in terms of protection
      against lipid peroxidation, protein oxidation, depletion of protein thiols and
      the levels of the antioxidant enzyme, superoxide dismutase. An active fraction
      consisting of polysaccharides (termed as P3) was effective even at a low
      concentration of 10 microg/ml. Both the crude extract as well as the P3 fraction
      significantly inhibited lipid peroxidation and protein oxidation. The antioxidant
      effect of P3 fraction was more pronounced against lipid peroxidation, as assessed
      by TBARS formation, while that of the crude extract was more effective in
      inhibiting protein oxidation. Both the crude extract and P3 fraction also partly
      protects against radiation-induced loss of protein thiols and inactivation of
      superoxide dismutase. The inhibitory effects of these active principles, at the
      concentration of 10 microg/ml, are comparable to that of the established
      antioxidants glutathione and ascorbic acid. Hence our results indicate that
      extracts from A. racemosus have potent antioxidant properties in vitro in
      mitochondrial membranes of rat liver.

PMID- 10940580
TI  - Cardiovascular activity of a methanolic extract of Digitalis purpurea spp.
      heywoodii.
AB  - The paper deals with the effects of a glycosidal extract of Digitalis heywoodii,
      ssp. of Digitalis purpurea L., (Schrophulariaceae) grown in Badajoz (Spain), on
      isolated cardiac auricle of rabbits, urinary excretion of rats, as well as its
      emetic effect in pigeons. These effects using vehicle (propylene glycol-ethanol
      water, 40:10:50) and digoxin as standards are presented. The extract at
      concentrations of 20 and 40 microg/ml produced an increase in the contraction
      force of auricles in a dose-dependent way. At doses of 15 and 30 mg/kg a slight
      diuretic and natriuretic effect was observed. The active dose range for emesis
      was 0.5-4 mg/kg and a decrease of the emesis time within 10 min of injection in
      dose-dependent manner was obtained. The pharmacological activity of the extract
      is related to gitoxin derivatives (digitalinum verum and strospeside), the most
      abundant compounds obtained from the leaves of Digitalis purpurea spp. heywoodii.

PMID- 10940581
TI  - Anti-inflammatory and analgesic activity of Biebersteinia multifida DC. root
      extract.
AB  - The root of Biebersteinia multifida DC (Geraniaceae), a native plant of Iran, has
      been used topically for the treatment of musculoskeletal disorders as a folk
      medicine. The anti-inflammatory and analgesic effects of the root extract were
      studied using carrageenan induced edema and formalin tests. A similar activity
      was seen between Biebersteinia multifida root extract (10 mg/kg; i.p.) and
      indomethacin (4 mg/kg; i.p.) in carrageenan test. The results of formalin test
      showed the analgesic activity of the root extract (50 mg/kg; i.p.) was comparable
      with morphine (10 mg/kg; i.p.) at the first phase of formalin test. Furthermore,
      the probable ulcerogenic activity of the root extract was also studied. The
      extract did not show any ulcerogenic effect at anti-inflammatory doses (10 mg/kg;
      p.o.).

PMID- 10940582
TI  - Structural modification of berberine alkaloids in relation to cytotoxic activity
      in vitro.
AB  - The cytotoxicity of two protoberberine alkaloids: berberine and lincangenine,
      their 8-hydroxy-7,8-dihydro-derivatives and tetrahydroprotoberberine:thaicanine,
      was evaluated. The cellular responses through the [3-(4,5-dimethylthiazol-2-yl)
      2,5-diphenyl-2H-tetrazolium bromide] (MTT) method were measured in Hela (uterus
      carcinoma), SVKO3 (ovary carcinoma), Hep-2 (larynx carcinoma), primary culture
      from mouse embryon, and human fibroblast cells at the concentration: 10-1000 ppm
      (microg/ml) for 24 h. Berberine showed the highest cytotoxicity among the
      compounds tested, giving LC50 values for all cell lines at the concentration of
      10 ppm. The results indicated that the cytotoxicity was notably decreased by
      structural changes, i.e. by modulation of the planarity caused by the
      introduction of hydroxyl group at C-8 and concomitant saturation of double bond
      between N-C8 in protoberberine molecules. In the case of berberine, the cytotoxic
      effect changed from 98.8 (berberine) to 39% for 8-hydroxydihydroberberine at the
      concentration of 100 ppm in Hela cells line. The same effect was observed with
      lincangenine and 8-OH-lincangenine (cytotoxicities 70 and 25%, respectively, at
      1000 ppm in SVKO3 cells). On the other hand, these compounds showed a low
      selectivity for the different human cancer cell lines tested.

PMID- 10940583
TI  - Coriandrum sativum--effect on lipid metabolism in 1,2-dimethyl hydrazine induced
      colon cancer.
AB  - The biochemical effect of coriander seeds on lipid parameters in 1,2-dimethyl
      hydrazine (DMH) induced colon cancer in rats were studied. The study shows that
      the concentrations of cholesterol and cholesterol to phospholipid ratio decreased
      while the level of phospholipid increased significantly in the DMH control group
      compared to the spice administered group. Fecal dry weight, fecal neutral sterols
      and bile acids showed a sharp increase in the coriander-fed group compared with
      the DMH administered group. Thus, coriander plays a protective role against the
      deleterious effects in lipid metabolism in experimental colon cancer.

PMID- 10940584
TI  - Experimental diuretic effects of Rosmarinus officinalis and Centaurium erythraea.
AB  - Herbal remedies are widely used in Moroccan pharmacopoeia. We assessed the
      diuretic effect of two medicinal plants: Rosmarinus officinalis L., Labiatae, and
      Centaurium erythraea L., Gentianaceae, both reputed for the treatment of urinary
      ailments. To determine the action of these herbs on urinary volume (UV) and the
      excretion of sodium (U(Na)V), potassium (U(K)V), and chloride (U(Cl)V), the
      aqueous extracts of both plants were administered daily to Wistar rats for 1
      week. The concentration of electrolytes and urea in plasma and creatinine
      clearance were also investigated. Daily oral administration of the aqueous
      extracts of R. officinalis and C. erythraea at the dose of 10 ml/kg of 8 or 16%
      extract in distilled water significantly enhanced diuresis in rats compared to
      the control group from the fifth day of treatment. For R. officinalis at the dose
      of 8% the peak of urinary excretion of sodium, potassium and chloride was reached
      after 6 days of treatment (P<0.001). The aqueous extract of of R. officinalis at
      the dose of 16% did not significantly affect the excretion of water and
      electrolytes over a similar period but slight increases in urinary excretion of
      sodium and chloride on the seventh day and of potassium on the sixth day (P<0.05)
      were observed. No increase was recorded for 24 h urinary excretion of Na+, K+ and
      Cl- during the first 4 days of treatment for the groups treated with C. erythraea
      at the doses of 8 and 16% whereas their effects on the same parameters were
      highly significant thereafter. No change was observed in plasma electrolytes and
      urea in any group, except for a decrease in sodium and chloride concentration in
      the group treated with 16% of R. officinalis. A decrease in creatinine clearance
      was demonstrated after treatment with 8% of R. officinalis and C. erythraea. Our
      findings demonstrate a diuretic effect of aqueous extracts of R. officinalis L.
      and C. erythraea L. with the most effective dose for water and electrolyte
      excretion being 8% for both plants.

PMID- 10940585
TI  - Cryptocarya species--substitute plants for Ocotea bullata? A pharmacological
      investigation in terms of cyclooxygenase-1 and -2 inhibition.
AB  - In response to the serious scarcity of Ocotea bullata (Burch.) Baillon
      (Lauraceae), an important medicinal plant in South Africa, Cryptocarya species
      (Lauraceae) are frequently used as substitute plants. Our investigation was aimed
      at a pharmacological comparison of O. bullata and the Cryptocarya species C.
      latifolia Sonder, C. myrtifolia Stapf., C. transvaalensis Burtt Davy, C. woodii
      Engl. and C. wyliei Stapf., in terms of in vitro cyclooxygenase-1 (COX-1) and
      cyclooxygenase-2 (COX-2) inhibition, as an indication of O. bullatas' repute as a
      remedy against headache. Furthermore, we also compared bark and leaf extracts of
      the species investigated in order to address the problem of destructive ring
      barking. The utilization of leaves instead of bark would help in the management
      of threatened medicinal plants. All Cryptocarya species were superior to O.
      bullata with regard to bark extracts. C. woodii bark extracts showed outstanding
      equipotent activity towards COX-1 and COX-2. The activity of extracts of fresh
      leaves was comparable to the activity of the respective bark extracts. Drying the
      leaves before extraction resulted in a loss of activity, with the exception of C.
      wyliei. Extracts of dried C. wyliei leaves exhibited high inhibitory activity,
      with a COX-2/COX-1 ratio of 5.8.

PMID- 10940586
TI  - Effect of Inula viscosa extract on chitin synthesis in dermatophytes and Candida
      albicans.
AB  - An antimycotic effect of an extract from Inula viscosa leaves was demonstrated
      affecting chitin synthesis in dermatophytes and Candida albicans. The antimycotic
      effect was compared to the effect caused by miconazole nitrate--an antifungal
      drug. The inhibition effect on chitin synthesis was not correlated to the extent
      of growth inhibition caused by the antifungal agents: both miconazole nitrate and
      the I. viscosa extract inhibited the growth of dermatophytes and C. albicans.
      Miconazole nitrate did not affect chitin synthesis--except for M. canis--whereas
      I. viscosa extract caused a significant decline in chitin content.

PMID- 10940587
TI  - Antioxidant activity of phenylethanoid glycosides from Brandisia hancei.
AB  - Brandisia hancei is a medicinal herb in China. The ethanol extract of this plant
      and four phenylethanoid glycosides, acteoside (1), 2'-acetylacteoside (2),
      poliumoside (3) and brandioside (4), isolated from it were shown to have
      inhibitory effects on free radical-induced hemolysis of red blood cells and free
      radical scavenging activities in vitro. Brandioside (4) and poliumoside (3)
      showed stronger antioxidant effect than acteoside (1), 2'-acetylacteoside (2) and
      trolox.

PMID- 10940588
TI  - Scilla maderensis, TLC screening and positive inotropic effect of bulb extracts.
AB  - Scilla maderensis Menezes (Hyacinthaceae) is endemic to the Portuguese
      Archipelago of Madeira. The taxonomic proximity between Scilla L. and Urginea
      Steinh. genus, and also the knowledge that bulbs of Urginea maritima (L.) Baker
      (Scilla maritima L.) contain cardiac glycosides of the bufadienolide type, led us
      to a phytochemical and pharmacological study of S. maderensis. Extracts obtained
      from the bulbs were screened by TLC and tested in the isolated frog heart
      preparation. The TLC screening revealed spots with colours and R(f) values
      similar to those obtained for proscillaridin and scillaren A. In the frog heart
      preparation the extracts showed a positive inotropic effect and toxic doses
      induced the arrest of the heartbeat in systole. We can conclude that the bulbs of
      S. maderensis contain substances exerting pharmacological effects on the heart.

PMID- 10940589
TI  - Snakebites and ethnobotany in the northwest region of Colombia: Part I:
      traditional use of plants.
AB  - In Antioquia and Choco, traditional healers attend 60% of snakebites. With the
      aim to produce an inventory of the plants used by the healers to treat snakebites
      and to document the methods of preparation, administration, the dosage, number of
      patients treated throughout their years of practice with treatment results, 20
      healers with experience in Bothrops, Porthidium and Bothriechis envenomations
      were interviewed between August, 1996 and November, 1998. They belong to nine
      black and three indigenous rural communities located near the towns of Bojaya,
      Vigia del Fuerte, Unguia (Atrato river valley), Nuqui and Bahia Solano (Pacific
      coast). Based on field interviews, 101 species of plants were identified as used
      to treat snakebites. The part used of each plant varies according to the species.
      Sixty plants are used in the form of drinks prepared by infusion, decoction or
      maceration; 78 as external baths on the affected extremity; 11 for steam
      application and 39 for poultices; the latter is used mainly when the bite is
      complicated by local necrosis. In mild and moderate envenomations, they generally
      use a mixture of three plants, while in severe cases they mix from five to 12, a
      handful of each one. Treatment is generally performed for 1-3 days, when the
      patient reacts positively. They reported to have treated 454 patients during
      their years of experience, 20 of them (4.4%) died. With the guidance of the
      healers, 77 species of plants were collected and photographed. These plants
      belong to 41 families, of which Piperaceae (13 species), Araceae (six species),
      Asteraceae (five species) and Gesneriaceae (three species) have the highest
      number of species.

PMID- 10940590
TI  - Snakebites and ethnobotany in the northwest region of Colombia: Part II:
      neutralization of lethal and enzymatic effects of Bothrops atrox venom.
AB  - Twelve of 74 ethanolic extracts of plants used by traditional healers for
      snakebites in the northwest region of Colombia, were active against lethal effect
      of Bothrops atrox venom when they were i.p. injected into mice (18-20 g). After
      preincubation of sublethal doses of every extract (0.5-4.0 mg/mouse) with 1.5
      i.p. lethal dose 50% (LD50) (99.3 microg) of venom, seven of them demonstrated
      100% neutralizing capacity within 48 h. These were the stem barks of Brownea
      rosademonte (Caesalpiniaceae) and Tabebuia rosea (Bignoniaceae); rhizomes of
      Renealmia alpinia (Zingiberaceae) and Heliconia curtispatha (Heliconiaceae); the
      whole plants of Pleopeltis percussa (Polypodiaceae) and Trichomanes elegans
      (Hymenophyllaceae); and the ripe fruits of Citrus limon (Rutaceae). The other
      five extracts showing partial neutralization (45-80%; 10-30% survival rate in the
      control group receiving the venom alone; P<0.05) were: leaves, branches and stem
      of Costus lasius (Costaceae); the whole plant of Sida acuta (Malvaceae); rhizomes
      of Dracontium croatii (Araceae); leaves and branches of Bixa orellana (Bixaceae)
      and Struthanthus orbicularis (Loranthaceae). When the extracts were independently
      administered per oral or i.p. route 60 min before an i.m. venom injection (204
      microg=1.5 i.m. LD50), C. limon, T. elegans, B. orellana and T. rosea extracts
      had partial and significant neutralizing capacity against B. atrox venom lethal
      effect. C. limon extract was also partially effective when it was administered
      either i.v. 15 min before or i.p. 5 min after an i.m. venom injection. Three of
      the 12 extracts with anti-lethal effect (C. limon, D. croatii and S. acuta) were
      devoid of antiphospholipase A2 activity, when they were tested against one
      minimum indirect hemolytic dose of B. atrox venom (2 microg) in agarose
      erythrocyte-egg yolk gels.

PMID- 10940591
TI  - Traditional uses of Salvia libanotica (East Mediterranean sage) and the effects
      of its essential oils.
AB  - The extract of sage (Salvia libanotica), a plant endemic to the Mediterranean
      region, is the most popular plant remedy used by the Middle Eastern people to
      treat common complaints such as colds and abdominal pain. This review paper
      describes the East Mediterranean sage plant, Salvia libanotica, its geographic
      distribution, essential oil components, and popular uses in traditional medicine.
      The paper also discusses the therapeutic value of the individual components
      present in the essential oil extract of this plant, and the complications that
      could arise from the irrational use of this extract by man.

PMID- 10940592
TI  - Alterations in the reproduction of mice induced by rapanone.
AB  - Oral administration of rapanone to a group of female mice at doses of 60 and 120
      mg/kg, reduced the percentage of pregnancies compared to control group,
      suggesting an anovulatory effect. Postcoital administration induced uterine
      alteration in both the first and second gestation periods. These results seem to
      indicate inhibition of trophoblast implantation in the first period, and an
      abortive effect and/or reabsorption in the second. Daily administration of
      rapanone to a group of male mice resulted in fertility alteration, which is
      attributed to an antispermatogenic effect. Rapanone did not show acute toxic
      effects at the doses tested in this research.

PMID- 10940593
TI  - Achyranthes aspera elevates thyroid hormone levels and decreases hepatic lipid
      peroxidation in male rats.
AB  - A study was made to evaluate the role of Achyranthes aspera on the changes in
      serum thyroid hormone concentrations and glucose levels in male rats. An attempt
      was also made to establish the relationship between hepatic lipid peroxidation
      and extract induced changes in thyroid hormone concentration, if any. Adult male
      Wistar rats were orally administered with the aqueous leaf extract of Achyranthes
      aspera at a dose of 200 mg/kg b. wt./day for 7 days. The effects of the extract
      on body weight, hepatic protein content, lipid peroxidation (LPO), superoxide
      dismutase (SOD) and catalase (CAT) activities and on serum triiodothyronine (T3),
      thyroxine (T4) and glucose levels were evaluated. The extract exhibited
      significant prothyroidic activity as it enhanced the levels of both the thyroid
      hormones along with an increase in serum glucose concentration, body weight and
      hepatic protein content. On the other hand, it decreased hepatic LPO without
      altering the activities of the two antioxidant enzymes, SOD and CAT
      significantly, suggesting a direct free radical scavenging activity of the
      extract. It appears that the Achyranthes aspera leaf extract is both prothyroidic
      and antiperoxidative in nature.

PMID- 10940595
TI  - Practical applications of genotypic surveys for forensic STR testing.
AB  - Legitimate genotype frequency estimation for multiallelic loci relies on
      component allele frequencies, as population surveys represent only a fraction of
      possible DNA profiles. Multilocus genotypes from two ethnic human populations,
      African American (n=195) and U.S. Caucasian (n=200), were compiled at 13 STR loci
      that are used worldwide in forensic investigation (D3S1358, vWA, FGA, D16S539,
      TH01, TPOX, CSF1PO, D8S1179, D21S11, D18S51, D5S818, D13S317, and D7S820). Sex
      specific AmpFlSTR multiplexes provided stringent PCR-based STR typing
      specifically optimized for multicolor fluorescence detection. Heterozygosity at
      each STR locus ranged from 0.57 to 0.89 and encompassed from seven (TH01) to
      twenty-one (D21S11) alleles. Homozygosity tests, tests based on the distinct
      numbers of observed homozygous and heterozygous classes, log likelihood ratio
      tests, and exact tests assessed that the degree of divergence from theoretical
      Hardy-Weinberg proportions for all 13 STRs does not have practical consequence in
      genotype frequency estimation. Departures from linkage equilibrium, between loci,
      that imposed significance to forensic calculations were not indicated by observed
      variance of the number of heterozygous loci or Karlin interclass correlation
      tests. For forensic casework, reliable multilocus profile estimates may be
      obtained from the product of component genotype frequencies, each calculated
      through application of the Hardy-Weinberg equation to population database allele
      frequency estimates reported here. The average probability that two randomly
      selected, unrelated individuals possess an identical thirteen-locus DNA profile
      was one in 1.8x10(15) African Americans and one in 3.8x10(14) U.S. Caucasians.

PMID- 10940596
TI  - DXYS267: DYS393 and its X chromosome counterpart.
AB  - The GATA repeat DYS393 was reported in 1987 among other Y-specific short tandem
      repeats. It has since been used for forensic and evolutionary studies. We decided
      to test its Y-specificity when we found that female DNA gave amplicons, in
      agreement with recent GDB-recorded experiences on radiation hybrids. Parent-child
      triplets revealed that heterozygous daughters always carried the same paternally
      derived amplicon which, however, was not amplified in their fathers' DNAs. The X
      assignment was verified in larger families. A half-new primer set with a new
      reverse DYS393 primer, outside the old one, resulted in X amplicons in females as
      well as Y and X amplicons in males. This new primer set defines the new DXYS267
      (GDB Data Curation). DNA-sequencing revealed four base pair differences between
      the Y- and the X-sequences. Two are within the reverse primer site sequence, thus
      probably causing preferential hybridization to the Y sequence when using the
      conventional primers. The two others are within the repeat array, giving the
      regular repeat GATA in the Y-sequence, and TATA and GACA, respectively, in the X
      sequence. Allele frequency distribution in DYS393 was studied in 300 unrelated
      Norwegian males, allele distribution in the X-locus in 48 Norwegian women. Even
      if allele repeat numbers are overlapping between the loci, leading to identical
      fragment lengths, the allele distribution is different between DYS393 and the X
      chromosome locus. The differences between the two homologous loci on the Y and X
      indicate a considerable lap of time since common ancestry. To avoid co
      amplification of the X-locus in DYS393 typing, primer A was elongated to include
      one of the sequence differences between the two loci. This to a considerable
      extent improved the specificity of the DYS393 primers.

PMID- 10940597
TI  - Identification of members of the genera Panaeolus and Psilocybe by a DNA test. A
      preliminary test for hallucinogenic fungi.
AB  - Abuse of hallucinogens produced by the fungal genera Psilocybe and Panaeolus are
      a growing problem. Five species from each of the two genera were examined in this
      preliminary research and a method that will unambiguously identify fungal samples
      as being of one of these two genera has been developed. The method uses genus
      specific DNA sequences within the Internal Transcribed Spacer of the ribosomal
      gene complex. Amplification of a common DNA product and a genus specific product
      results in two identifiable products, which facilitates the unambiguous
      identification of material from these two fungi to generic level.

PMID- 10940598
TI  - The transfer of petrol on to clothing and shoes while pouring petrol around a
      room.
AB  - This study was aimed at measuring the approximate amount of petrol transferred on
      to the clothing and shoes of a person during the action of pouring petrol around
      a room. Two different heights of pouring and two different types of floor surface
      (carpet and concrete) were investigated. Results show that for all the
      combinations examined petrol was always transferred to the shoes and often
      transferred to the upper and lower clothing. This information illustrates the
      necessity of analysing the clothing and particularly the shoes of any suspected
      arsonists for the presence of hydrocarbon fuels.

PMID- 10940599
TI  - Salvia divinorum: an hallucinogenic mint which might become a new recreational
      drug in Switzerland.
AB  - Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for
      curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from
      Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana
      substitute. Recently, two S. divinorum specimens were seized in a large-scale
      illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin
      A, a trans-neoclerodane diterpene, was identified in several organic solvent
      extracts by gas chromatography-mass spectrometry. The botanical identity of the
      plant was confirmed by comparing it to an authentic herbarium specimen. More
      plants were then discovered in Swiss horticulturists greenhouses. All these data
      taken together suggest that many attempts exist in Switzerland to use S.
      divinorum as a recreational drug. This phenomenon may be enhanced because neither
      the magic mint, nor its active compound are banned substances listed in the Swiss
      narcotic law.

PMID- 10940600
TI  - Validation of the AMPFlSTR SGM plus system for use in forensic casework.
AB  - The AMPFlSTR((R)) SGM Plus system is a commercially available STR multiplex
      produced by Applied Biosystems, a division of Perkin Elmer, Foster City,
      California, USA that supersedes SGM. The multiplex contains the six SGM loci,
      amelogenin and four additional loci. These additional loci are D3S1358, D19S433,
      D16S539 and D2S1338. Consequently, the match probability is significantly
      improved (conservatively quoted as 1 in 10(9) for reporting a full profile
      match). The system was subjected to validation. For example, ageing and
      degradation studies demonstrated semen stains to be the most stable evidence
      type, whereas buccal scrapes were the least stable. An apparent rise in the
      sensitivity increases the chance of obtaining successful results from the more
      difficult samples submitted for analysis. Two of the new loci (D3S1358 and
      D19S433) are low molecular weight (between 100 and 150 base pairs); this improved
      the success rates of the degraded samples where high molecular weight loci may
      drop out. Of 26 non-primates tested, four gave results that appeared as single
      peaks and were unlikely to cause interpretation problems. None of the 19 micro
      organisms tested gave discernible results. Extensive casework and simulated
      casework studies demonstrated that SGM and SGM plus results were comparable.
      There was one example of a null allele (primer binding site mutation) recorded at
      the HUMFIBRA locus (in both systems). However, a concordance study of 1000
      samples using both SGM and SGM plus did not demonstrate any differences in
      typing.

PMID- 10940601
TI  - The prevalence of analgesics containing dextropropoxyphene or codeine in
      individuals suspected of driving under the influence of drugs.
AB  - To investigate the prevalence of analgesics containing dextropropoxyphene (DXP)
      or codeine in individuals suspected of driving under the influence of drugs, we
      analysed all blood samples in which drugs were screened for in cases of suspected
      drunken driving in Sweden during the years 1992-1997. DXP was found in 130 (2.7%)
      and codeine in 388 (7.9%) of the 4896 drug-screened cases. The ratio between the
      number of DXP and of codeine cases and prescription of defined daily dose/1000
      inhabitants during a 12-month period (DDD) was determined. The quotient for DXP
      was trebled from 1992 (0.99) to 1997 (2.89), while the codeine quotient decreased
      by 9% (from 6 to 5.5). The blood samples showed polydrug use in all but 28 cases
      of the 486 cases where DXP and/or codeine was found. In 71% of the 486 cases
      benzodiazepines were also present and in 38% of the cases amphetamine and/or
      cannabis were present. It was concluded that analgesics containing DXP or codeine
      are not drugs of primary interest in this specific population. Nevertheless,
      because of the high toxicity of DXP, especially when combined with alcohol or
      other drugs, the increase in the DXP prevalence gives reason for concern, since
      the studied population represents a group of individuals who use large doses of
      therapeutic or illegal drugs.

PMID- 10940603
TI  - Genetic variation and relationships at five STR loci in five distinct ethnic
      groups in China.
AB  - Five short tandem repeat (STR) systems of TH01, vWA, LPL, F13B and FES/FPS were
      investigated in five ethnic groups living in China (Tujia, Miao, Bai, Chaoxian
      and Han). All five loci did not deviate from the Hardy-Weinberg equilibrium
      (P>0.05). At the five loci of each ethnic group, the observed heterozygosity, the
      mean exclusion chance (MEC), and the power of discrimination (PD) ranged from
      0.42 to 0.86, from 0.20 to 0.66 and from 0.61 to 0.95, respectively. For the five
      ethnic groups, the combined MEC and combined PD were >0. 9360 and >0.9998,
      respectively, suggesting that combinations of these five systems are feasible for
      DNA typing in forensic investigations such as personal identification or
      paternity testing. Furthermore, the allelic frequencies at the five loci
      suggested that these five ethnic groups were distinctly different communities.
      Judging from the phylogenetic tree constructed based on the genetic distance
      among the five ethnic groups, Han, Chaoxian and Tujia were involved in an
      identical cluster, and Miao and Bai in another. These findings indicate that each
      of the five groups examined is not only a distinct community, but also has a
      relationship with each of the others.

PMID- 10940602
TI  - The effects of sarin-like and soman-like organophosphorus agents on MAPK and JNK
      in rat brains.
AB  - One sarin-like and one soman-like organophosphorus agent [bis(isopropyl
      methyl)phosphonate, BIMP and bis(pinacolyl methyl)phosphonate, BPMP] were
      injected intravenously (iv) in rats. An increase in the tyrosine phosphorylation
      of several proteins in the cytosol fraction of the brain was observed. Activation
      of c-Jun N-terminal kinase (JNK) and slight activation of mitogen-activated
      protein kinase (MAPK) in the cytosol were also observed. The activation of these
      enzymes may be related to the high toxicity of these nerve agents.

PMID- 10940604
TI  - Benzodiazepine findings in blood and urine by gas chromatography and immunoassay.
AB  - Gas chromatography (GC) and immunoassay techniques applied to blood and urine
      specimens were compared for the screening of benzodiazepines in postmortem
      forensic toxicology. Five hundred and six such successive postmortem cases in
      which both urine and peripheral blood was sent for toxicological analysis by the
      medical examiners were selected. The urine specimens were tested by the Emit((R))
      d.a.u. Benzodiazepine Assay, and in parallel, the blood and urine specimens were
      screened for benzodiazepine drugs and their metabolites by an established
      automated dual-column GC method. The lowest number of positives (153) was
      obtained when immunoassay was performed without enzyme hydrolysis. When urine
      samples were hydrolysed before immunoassay, the number of positives increased to
      175. The highest number of positives (200) was obtained in urine by GC, and the
      screening of blood by GC yielded 185 quantitative results. Despite the urine GC
      screening produced the most positives, the quantitative screening of the blood by
      GC appears to be the most efficient approach in postmortem forensic toxicology,
      considering the fact that although urine findings confirm the presence of the
      drug, quantitative results in urine are irrelevant to acute toxicity.

PMID- 10940606
TI  - A self-learning segmentation framework--the Taguchi approach.
AB  - The detection of object boundary is an interesting and challenging task in
      computer vision and medical image processing. The active contour model (snake
      model) has attracted much attention for object boundary detection in the past
      decade. However, due to the lack of understanding on the effect of different
      energy terms to the behavior of related objective functions for an image, the
      assignment of weights for different energy terms in this model is usually
      fulfilled empirically. Few discussions have been brought out specifically for
      assigning these weights automatically. In this paper, a novel self-learning
      segmentation framework, based on the snake model is proposed and applied to the
      detection of cardiac boundaries from ultrasonic images. The framework consists of
      a learning section and a detection section, and provides a training mechanism to
      obtain the weights from a desired object contour given manually. This mechanism
      first employs Taguchi's method to determine the weight ratios among distinct
      energy terms, followed by a weight refinement step with a genetic algorithm. The
      refined weights can be treated as the a priori knowledge embedded in the manually
      defined contour and be used for subsequent contour detection. Experiments with
      both synthetic and real echocardiac images were conducted with satisfactory
      outcomes. Results also show that the present method can be used to analyze
      successive images of the same object with only one training contour. Finally, the
      validity of the weight determining process was verified by the analysis of
      variance method (ANOVA).

PMID- 10940605
TI  - Fatal acute alcohol intoxication in an ALDH2 heterozygote: a case report.
AB  - On an evening in November, a 25-year-old man was found dead in his bedroom. There
      were many empty snap-out sheets for flunitrazepam tablets in the trash at his
      bedside. He had been beaten by a gang of young people earlier in the morning of
      the same day. At the medico-legal autopsy, although there were many bruises
      and/or abrasions on the whole body, only slight subdural hemorrhage was observed,
      and none of them was thought to be the cause of death. Flunitrazepam and its
      metabolites were not detected in his body fluid by gas chromatography-mass
      spectrometry (GC-MS). Marked lung edema and a severe congestion of organs were
      observed. His blood alcohol concentration from the femoral vein was 2.00 mg/ml.
      Fatal cases of acute alcohol intoxication usually have shown higher alcohol
      concentration (2.25-6.23 mg/ml). Although the genotype of aldehyde dehydrogenase
      2 (ALDH2) has not previously been mentioned as a contributing factor in
      determining the cause of death, in this case the genotype of ALDH2 was ALDH2*1/2
      and thus is important. Those who possess the ALDH2*2 gene show high
      concentrations of acetaldehyde (AcH) at even comparatively lower alcohol levels.
      Consequently, the cause of death was considered to be acute alcohol intoxication
      including AcH poisoning.

PMID- 10940607
TI  - Digital hand atlas and web-based bone age assessment: system design and
      implementation.
AB  - Bone age assessment is a procedure frequently performed in pediatric patients to
      evaluate their growth disorder. A simple method commonly used in bone age
      assessment is atlas matching by a radiological examination of a left-hand
      radiograph against a small reference set of Greulich-Pyle atlas patterns of
      normal standards. The method however can lead to significant deviation in age
      assessment, due to a variety of observers with different levels of training. The
      Greulich-Pyle atlas developed in the 1950s based on middle upper class white
      populations, is also not fully applicable for children of today, especially
      regarding the standard development in other racial groups. In this paper, we
      present our system design and initial implementation of a digital hand atlas and
      computer-aided diagnostic (CAD) system for Web-based bone age assessment. The CAD
      system is built on top of existing picture archiving and communication system
      (PACS), as well as recent advances in Internet technology. It consists of a hand
      atlas database, a CAD module and a Java-based Web user interface. The digital
      atlas is based on a large new set of clinically normal hand images of diverse
      ethnic groups. A relational image database system is used to organize hand
      images, their extracted quantitative features and patient data. The digital atlas
      removes the disadvantages of the currently out-of-date Greulich-Pyle atlas and
      allows the bone age assessment to be computerized. The Java-based Web user
      interface allows users to interact with the hand image database from browsers.
      Users can use a Web browser to push a clinical hand image to the CAD server for a
      bone age assessment. Quantitative features on the examined image, which reflect
      the skeletal maturity, are then extracted and compared with patterns from the
      atlas database to assess the bone age. The digital atlas method based on open
      system Internet technology provides an alternative to supplement or replace the
      traditional one for a quantitative, accurate and cost-effective assessment of
      bone age.

PMID- 10940608
TI  - Comparison of echo planar imaging, gradient echo and fast spin echo MR scans of
      knee menisci.
AB  - In order to reduce the acquisition time, we compared a three-dimensional multi
      shot echo-planar imaging (EPI) sequence with fat-suppression with two widely used
      sequences, the fat-suppressed gradient echo (GRE) and the proton-density weighted
      turbo spin-echo (FSE) in imaging the menisci of the knee. Sixty patients with
      various indications were studied prospectively with MRI. The menisci were imaged
      in the sagittal plane with all three sequences using a 1T MR scanner with 15mT/m
      gradients. The signal-to-noise ratio (SNR) of bone (b), cartilage (c), and
      meniscus (m) as well as contrast-to-noise ratio (CNR) and relative contrast
      (ReCon) between menisci and cartilage and between bone and cartilage were
      measured. A qualitative analysis was performed on grading of meniscal pathology
      (0-IV). The imaging accuracy of meniscal pathology was assessed compared to
      arthroscopy in 13 patients. The EPI provided the highest SNR in cartilage and
      meniscus (p<0.001), the highest CNR and the highest ReCon between bone and
      cartilage (p< or =0.001). MR grading of meniscal abnormalities showed
      overestimation compared to GRE and FSE. The EPI sequence could not be included in
      the routine protocol in imaging the menisci since the overestimation of meniscal
      abnormalities could lead to unnecessary arthroscopy.

PMID- 10940609
TI  - Prediction of optimal injection protocol for tumor detection in contrast-enhanced
      dynamic hepatic CT using simulation of lesion-to-liver contrast difference.
AB  - The detection of hepatic lesions in computed tomography (CT) is improved when a
      contrasting material is administered intravenously, but it depends considerably
      on how this agent is injected. In this study, we constructed a compartment model
      for a liver containing a hepato-cellular carcinoma (HCC), and simulated the
      difference in lesion-to-liver contrast enhancement. Using this model, we
      simulated the effects of various injection factors on the detectability of a
      lesion and searched for the optimal injection protocol for detecting tumors in
      contrast-enhanced dynamic hepatic CTs. We found that the mass injection rate, or
      k-value (in mg/s), (which is the volume injection rate, in ml/s, multiplied by
      the contrast agent concentration, in mg/ml) plays a critical role in the
      injection protocol optimized for tumor detection, and has a unique value for a
      given body weight independent of the total injection dose.

PMID- 10940611
TI  - Fluid-attenuated inversion-recovery imaging of cerebral infarction associated
      with tuberculous meningitis.
AB  - A 12-month-old girl presented with fever and vomiting. Cerebrospinal fluid (CSF)
      examination revealed an increase of mononuclear cells and Mycobacterium
      tuberculosis. Magnetic resonance imaging (MRI) taken two months after the onset
      showed cerebral infarction in the left basal ganglia, tuberculoma in the
      interpeduncular cistern and brain atrophy. The infarction was shown as central
      cystic lesions with surrounding hyperintensity in the fluid-attenuated inversion
      recovery (FLAIR) image. The cystic lesions were not differentiated from
      surrounding lesions in T2 weighted image (T2WI) because both lesions were
      demonstrated as hyperintensity areas. The hyperintensity lesion shown in FLAIR
      image may indicate border zone encephalitis. The FLAIR image is more useful than
      T1 or T2WI to detect the extension of the infarcted area and circumscribed
      change.

PMID- 10940610
TI  - Malignant fibrous histiocytoma of the spine causing spinal neural foramen
      widening.
AB  - A case with a clinical picture of a chronic low back pain radiating to both
      lumbar regions caused by malignant fibrous histiocytoma is reported.
      Radiological, surgical and histopathological findings and treatment of this rare
      case are discussed.

PMID- 10940612
TI  - Imaging of primary rhabdomyosarcoma of the diaphragm.
AB  - This is a report on a rare case of embryonal rhabdomyosarcoma involving the
      diaphragm in a 3-year-old boy. This case illustrates the importance of
      preoperative imaging in the management of this tumor.

PMID- 10940613
TI  - Reliability and clinical usefulness of the short-forms of the Wechsler memory
      scale (revised) in patients with epilepsy.
AB  - PURPOSE: The Wechsler Memory Scale-R (WMS-R) is often used for the evaluation of
      patients with epilepsy, but is time consuming. Two shortened forms of the WMS-R
      have been published in an effort to reduce the time involved in the test. The
      purpose of this study is to cross-validate these abbreviated forms in patients
      with epilepsy. METHODS: We assessed 103 consecutive patients with drug-resistant
      partial epilepsy being treated in our epilepsy unit. The WMS-R was administered
      to all patients. The reliability of two shortened versions of the WMS-R were
      evaluated. The appraisal was performed taking into account the side of the
      epileptogenic region. The statistical analyses were carried out with the
      Pearson's correlation and with the intraclass correlation coefficient. RESULTS:
      Both shortened formulas showed good reliability coefficients for predicting the
      General Memory and Delayed Recall Indices. In the overall accuracy of the
      predictions by both short forms no significant differences were found among the
      three study. groups (right, left or bilateral). However, when considering the
      predictive error only the three-subtest formulas comprising logical memory,
      verbal paired associates and visual reproduction efficiently predicted
      performance, regardless of the side of the epileptogenic region. Of the predicted
      scores in the overall sample, 92 and 97% fell below the standard error of
      measurement for general and delayed memory index, respectively. Both short forms
      correctly classified 89-94% of the performances at the average or impaired level.
      CONCLUSIONS: The short form of the M-MS-R using three subtests (logical memory,
      verbal paired associates and visual reproduction) is reliable and time-efficient
      for estimating the General and Delayed Recall Memory indexes in patients with
      drug-resistant partial epilepsy.

PMID- 10940614
TI  - Assessing risk to benefit ratio in antiepileptic drug therapy.
AB  - Assessment of risk to benefit ratio in patients with epilepsy is crucial in
      determining the need for treatment, the choice of drugs and the use of monitoring
      tools such as laboratory tests and other investigations. Active epilepsy per se
      carries significant risks in terms of increased mortality, susceptibility to
      psychopathology and physical injury, and reduced quality of life as a result of
      restricted lifestyle, stigma and prejudice. By preventing the occurrence of
      seizures, antiepileptic drugs (AEDs) attenuate or eliminate altogether seizure
      related risks, but other risks may arise due to the side effects of the drugs,
      all of which have a relatively narrow therapeutic index. While there are no major
      differences in the degree of efficacy between AEDs which are effective in any
      given seizure type, side effect profiles differ considerably from one agent to
      another and represent a major factor in determining choice of treatment.
      Assessment of risk to benefit ratio should also take into consideration patient
      specific factors such as type and severity of the epilepsy, age, sex,
      childbearing potential, medical and drug history, associated disease, use of
      concomitant medication (including the contraceptive pill) and the prospected
      patient's compliance. In some benign epilepsy syndromes, such as idiopathic
      partial epilepsy with centro-temporal spikes, the risk of side effects from AEDs
      may outweigh potential benefits in terms of seizure control, and treatment is
      generally not indicated. At the opposite end of the spectrum, the serious
      morbidity and mortality associated with severe epileptic encephalopathies, such
      as the Lennox-Gastaut syndrome, justifies aggressive treatment even with drugs
      associated with a relatively high risk of life threatening side effects such as
      felbamate. The present article will provide an overview of specific risks
      associated with epilepsy and with the various drugs used for its treatment, and
      will attempt to evaluate the complex balance between these risks and therapeutic
      benefits in different categories of patients.

PMID- 10940615
TI  - Sequential expression of surface antigens and transcription factor NFkappaB by
      hippocampal cells in excitotoxicity and experimental epilepsy.
AB  - Neurodegeneration and gliosis have been extensively described after long-lasting
      seizures; evidence for cytokine involvement in neuron-glia interactions does
      exist. We have therefore studied the hippocampal expression of molecules
      responsible for immune and inflammatory reactions, at different time-points
      following either experimental status epilepticus (SE) or direct excitotoxic
      damage. Experiments consisting of immunohistochemical labeling of glial markers,
      major histocompatibility complex (MHC) and nuclear factor kappaB (NFkappaB), were
      performed. NFkappaB nuclear translocation was controlled and measured using the
      electrophoretic mobility shift assay. One day after SE, neurodegeneration was
      obvious in CA3 pyramidal layers; NFkappaB staining in neurons and its
      translocation to the nucleus enhanced. From day 4 to at least day 8 post-SE, MHC
      positive microglia, NFkappaB over-expression in thickened astrocytes, and
      increased levels of its activated form could be observed. The excitotoxic model
      caused more severe lesions, but NFkappaB and MHC expression were similar in both
      models. These results suggest that during long-lasting seizures: (i) neuronal
      firing activates NFkappaB expression and translocation; (ii) microglia expresses
      MHC; (iii) astrocytes, probably stimulated by microglial cytokines, over-express
      NFkappaB, the activation of which induces a cascade of reactions, particularly
      the transcription of cytokines and or neuroprotective molecules. Further
      clarification of the toxic or protective consequences of delayed inflammatory
      responses may be interesting in therapy of epilepsy.

PMID- 10940616
TI  - The effects of gabapentin in the rat hippocampus are mimicked by two structural
      analogs, but not by nimodipine.
AB  - Gabapentin has been shown to reduce paired-pulse inhibition in the dentate gyrus
      of the urethane-anesthetized rat and has been shown to block calcium channels,
      but its not known how these possible mechanisms relate to its antiepileptic
      effect. Here, we tested two structural analogs of gabapentin for the ability to
      reduce seizure duration and to alter paired-pulse inhibition in the dentate gyrus
      in urethane anesthetized adult Sprague-Dawley rats. We compared with our results
      to those with diazepam, an anxiolytic and GABA(A) positive modulator and with
      nimodipine, a specific blocker of L-type Ca2+ channels. Both structural analogs
      of gabapentin caused a dose-dependent loss of paired-pulse inhibition and blocked
      the lengthening of the duration of the seizure discharge. Nimodipine also blocked
      the increase in duration of the seizure discharge, but increased paired-pulse
      inhibition. The effects of the GABA derivatives on paired-pulse inhibition and on
      seizure duration may have a common mechanism. Furthermore, our results indicate
      that gabapentin's postulated block of L-type calcium channels is not responsible
      for reducing paired-pulse inhibition. However, calcium channel block could still
      be the basis for the antiepileptic effect of gabapentin and its analogs.

PMID- 10940617
TI  - Polycystic ovary syndrome in patients with focal epilepsy: a study in 93 women.
AB  - A prospective cohort analysis of premenopausal women with focal epilepsy was
      conducted in order to determine whether polycystic ovary syndrome (PCOS) is a
      common finding in women treated with antiepileptic drugs (AED). This study was
      carried out in 93 of 150 women (aged between 20 and 53 years; mean, 34.3 years)
      with chronic focal epilepsy consecutively cared for at the Department of
      Epileptology, University of Bonn: 38 were receiving one AED (18 valproate, 20
      carbamazepine), 36 more than one drug, and 19 were without medication. Patients
      were followed-up for 6 months. PCOS was defined as hyperandrogenism (testosterone
      concentration, > 0.7 ng/ml) combined with oligomenorrhoea (cycle length, > 35
      days) or amenorrhoea. PCOS was identified in two out of 19 (10.5%) patients
      receiving no medication; in four of 38 (10.5%) of patients receiving monotherapy,
      and in none of the patients receiving more than one AED. The incidence of PCOS in
      patients treated with valproate monotherapy (11.1%) was similar to that in
      patients treated with carbamazepine (10%) and also to that in patients not
      treated with AEDs. The results of this study suggest that the manifestation of
      PCOS in women with focal epilepsy is not related to the administration of
      valproate or carbamazepine.

PMID- 10940618
TI  - Usefulness of 3-D reconstructed images of the human cerebral cortex for
      localization of subdural electrodes in epilepsy surgery.
AB  - Three-dimensional (3-D) images of 14 patients, in whom subdural electrodes were
      implanted for epilepsy surgery evaluation, were produced by fusing computerized
      tomography (CT) scans and magnetic resonance images (MRI) to determine the exact
      location of the electrodes. In 25% (198 of 806) of the subdural electrodes an
      exact location for resection strategy was not evident from the X-rays. The
      location of these electrodes ('doubtful location', DL) was compared to the 3-D
      images. Intraoperative inspection served as the gold standard. Concordance score
      was defined as good for 75-100% concordance, moderate for 50-75%, and poor for
      less than 50% concordance of the DL electrodes to the intraoperatively determined
      location. A comparative analysis of the 3-D images and X-ray films showed a
      highly significant difference (P < 0.0002) in favor of 3-D images. The
      concordance score for the DL electrodes in the 3-D images was good in 93% of the
      patients and moderate in 7%. In contrast, the concordance score was good in only
      7% of the patients for the two-dimensional (2-D) skull films, moderate in 57%,
      and poor in 36%. Interobserver reliability was better for 3-D images (93%) than
      for the 2-D X-rays (43%). These findings suggest that 3-D images aid preoperative
      planning for resective epilepsy surgery.

PMID- 10940619
TI  - Motor cortex excitability in patients with focal epilepsy.
AB  - We studied the excitability of the motor cortex using, transcranial magnetic
      stimulation (TMS) in patients with temporal and extratemporal epilepsy. We
      applied single and paired-pulse TMS to 15 patients with temporal (n = 7),
      extratemporal (n = 6) and focal epilepsy lateralised to one hemisphere (n = 2).
      Patients had no antiepileptic drugs in the last 48 h and were seizure free for 4
      h prior to testing. We determined the threshold for EMG responses at rest (RMT),
      the cortically evoked silent period (CSSP) and intracortical inhibition (ICI,
      intervals of 2-4 ms) and facilitation (ICF, 7-15 ms) and compared the results to
      those obtained in 17 normal controls. ICI and ICF was reduced in both hemispheres
      (P < 0.01. ANOVA) compared to the controls. In the hemisphere of seizure origin
      ('abnormal') there was a reduction of ICF (P < 0.01) and normal ICI, in the
      'normal' hemisphere there was a reduced ICI (P < 0.01) and a slight reduction of
      ICF (P < 0.05). ICF on the 'abnormal' side was reduced (P < 0.05) compared to the
      'normal' hemisphere. RMT was increased in two patients, but group comparison of
      RMT and CSSP showed no significant differences between patients and controls. The
      results suggest a remote effect of epileptic activity onto the motor cortex
      leading to an alteration of activity in local inhibitory circuits.

PMID- 10940620
TI  - Xotx5b, a new member of the Otx gene family, may be involved in anterior and eye
      development in Xenopus laevis.
AB  - We describe the cloning, expression pattern and functional overexpression
      analysis of Xotx5b, a new member of the Otx gene family in Xenopus laevis. Early
      expression of Xotx5b resembles that of Xotx2, being detected in the organizer
      region at early gastrula stage, and, shortly after, also in anterior
      neuroectoderm. During neurula stages Xotx5b exhibits a changing and dynamic
      pattern of expression. After neural tube closure, Xotx5b is expressed in the eye
      and pineal gland, both involved in photoreception. Overexpression of Xotx5b has a
      similar effect to that of Xotx2, producing posterior truncations and inducing
      ectopic cement gland and neural tissue in whole embryos. In animal cap assays,
      Xotx5b and Xotx2 are both able to activate XAG, to strongly suppress the
      expression of the epidermal marker XK81, and to reciprocally activate each other.
      Finally, in einsteck transplantation assays, Xotx5b is able to respecify a
      tail/trunk organizer to a head organizer.

PMID- 10940621
TI  - homothorax and iroquois-C genes are required for the establishment of territories
      within the developing eye disc.
AB  - In Drosophila the eye-antennal disc gives rise to most adult structures of the
      fly's head. Yet the molecular basis for its regionalization during development is
      poorly understood. Here we show that homothorax is required early during
      development for normal eye development and is necessary for the formation of the
      ventral head capsule. In the ventral region of the disc only, homothorax and
      wingless are involved in a positive feedback loop necessary to restrict eye
      formation. homothorax is able to prevent the initiation and progression of the
      morphogenetic furrow without inducing wingless, which points to homothorax as a
      key negative regulator of eye development. In addition, we show that the iroquois
      complex genes are required for dorsal head development antagonizing the function
      of homothorax in this region of the disc.

PMID- 10940622
TI  - Expression of the blistered/DSRF gene is controlled by different morphogens
      during Drosophila trachea and wing development.
AB  - The Drosophila serum response factor (DSRF) is expressed in the precursors of the
      terminal tracheal cells and in the future intervein territories of the third
      instar wing imaginal disc. Dissection of the DSRF regulatory region reveals that
      a single enhancer element, which is under the control of the fibroblast growth
      factor (FGF)-receptor signalling pathway, is sufficient to induce DSRF expression
      in the terminal tracheal cells. In contrast, two separate enhancers direct
      expression in distinct intervein sectors of the wing imaginal disc. One element
      is active in the central intervein sector and is induced by the Hedgehog
      signalling pathway. The other element is under the control of Decapentaplegic and
      is active in two separate territories, which roughly correspond to the intervein
      sectors flanking the central sector. Hence, each of the three characterized
      enhancers constitutes a molecular link between a specific territory induced by a
      morphogen signal and the localized expression of a gene required for the final
      differentiation of this territory.

PMID- 10940623
TI  - The decapentaplegic morphogen gradient regulates the notal wingless expression
      through induction of pannier and u-shaped in Drosophila.
AB  - The morphogen gradient of Wingless, a Wnt family member protein, provides
      positional information to cells in Drosophila imaginal discs. Elucidating the
      mechanism that precisely restricts the expression domain of wingless is important
      in understanding the two-dimensional patterning by secreted proteins in imaginal
      discs. In the pouch region of the wing disc, wingless is induced at the
      dorsal/ventral compartment boundary by Notch signaling in a compartment-dependent
      manner. In the notum region of the wing disc, wingless is also expressed across
      the dorsal/ventral axis, however, regulation of notal wingless expression is not
      fully understood. Here, we show that notal wingless expression is established
      through the function of Pannier, U-shaped and Wingless signaling itself. Initial
      wingless induction is regulated by two transcription factors, Pannier and U
      shaped. At a later stage, wingless expression expands ventrally from the pannier
      expression domain by a Wingless signaling-dependent mechanism. Interestingly,
      expression of pannier and u-shaped is regulated by Decapentaplegic signaling that
      provides the positional information along the anterior/posterior axis, in a
      concentration-dependent manner. This suggests that the Decapentaplegic morphogen
      gradient is utilized not only for anterior/posterior patterning but also
      contributes to dorsal/ventral patterning through the induction of pannier, u
      shaped and wingless during Drosophila notum development.

PMID- 10940624
TI  - Tight junction biogenesis in the early Xenopus embryo.
AB  - Tight junctions (TJs) perform a critical role in the transport functions and
      morphogenetic activity of the primary epithelium formed during Xenopus cleavage.
      Biogenesis of these junctions was studied by immunolocalization of TJ-associated
      proteins (cingulin, ZO-1 and occludin) and by an in vivo biotin diffusion assay.
      Using fertilized eggs synchronized during the first division cycle, we found that
      membrane assembly of the TJ initiated at the animal pole towards the end of
      zygote cytokinesis and involved sequential incorporation of components in the
      order cingulin, ZO-1 and occludin. The three constituents appeared to be
      recruited from maternal stores and were targeted to the nascent TJ site by
      different pathways. TJ protein assembly was focused precisely to the border
      between the oolemma-derived apical membrane and newly-inserted basolateral
      membrane generated during cytokinesis and culminated in the formation of
      functional TJs in the two-cell embryo, which maintained a diffusion barrier. New
      membrane formation and the generation of cell surface polarity therefore precede
      initiation of TJ formation. Moreover, assembly of TJ marker protein precisely at
      the apical-basolateral membrane boundary was preserved in the complete absence of
      intercellular contacts and adhesion. Thus, the mechanism of TJ biogenesis in the
      Xenopus early embryo relies on intrinsic cues of a cell autonomous mechanism.
      These data reveal a distinction between Xenopus and mammalian early embryos in
      the origin and mechanisms of epithelial cell polarization and TJ formation during
      cleavage of the egg.

PMID- 10940626
TI  - Murine hoxd4 expression in the CNS requires multiple elements including a
      retinoic acid response element.
AB  - We have identified a retinoic acid response element (RARE) within a neural
      enhancer located 3' to the Hoxd4 gene. This RARE is required for the initiation
      and maintenance of Hoxd4 transgene expression in neurectoderm, and for full
      anteriorized expression upon retinoic acid (RA) treatment. Mutations within the
      sequence TTTTCTG, located 2 bp downstream of the RARE, posteriorized transgene
      activity. However, the onset of transgene expression and its response to RA were
      indistinguishable from wild type. While the TTTTCTG motif resembles a CDX binding
      site, human CDX1 protein did not interact with this element in vitro. Three
      additional regions were also shown to control transgene expression in
      neurectoderm, establishing that multiple elements constitute the Hoxd4 neural
      enhancer.

PMID- 10940625
TI  - Domina (Dom), a new Drosophila member of the FKH/WH gene family, affects
      morphogenesis and is a suppressor of position-effect variegation.
AB  - Domina (Dom) is a novel member of the FKH/WH transcription factor gene family of
      Drosophila. Two alternatively polyadenylated Dom transcripts of 2.9 and 3.9 kb
      encode a 719-amino-acid protein with a FKH/WH domain and a putative acidic
      transactivation domain. Dom is mainly expressed in the central and peripheral
      nervous system. Homozygous mutants show rough eyes, irregular arrangement of
      bristles, extended wings, defective posterior wing margins, and a severely
      diminished vitality and fertility. Heterozygous Dom flies are morphologically
      wild type but show suppression of position-effect variegation. Consistently with
      this chromatin effect DOM protein is accumulated in the chromocenter and, as
      expected from a transcription factor, is found at specific euchromatic loci.
      Sequence comparison suggests that DOM of Drosophila is homologous to the chordate
      WHN proteins. The chromatin modifying capability of DOM is probably based on the
      FKH/WH domain, which shows a remarkable structural similarity to the winged-helix
      structures of H1 and the central globular domain of H5.

PMID- 10940627
TI  - Human SPRY2 inhibits FGF2 signalling by a secreted factor.
AB  - Growth factor signalling pathways and their inhibitors coordinate the formation
      of three-dimensional patterns of vertebrates and invertebrates. Temporal and
      spatial restriction of the response to a few well-defined cells is crucial and
      needs the integration of positive and negative signals. Recently, Spry has been
      identified as an inhibitor of fibroblast growth factor (FGF) signalling during
      Drosophila trachea development. Spry has been described as an intracellular
      protein that can exert its function in a cell autonomous or a paracrine manner.
      Here we describe the role of SPRY2, a human homologue of Spry, in human FGF2
      signalling. We show that in primary human dermal endothelial cells (MVEC) SPRY2
      mRNA is transiently upregulated in response to FGF2. Overexpression of SPRY2 in
      A375 cells leads to the secretion of a soluble factor that inhibits FGF2- but not
      VEGF-stimulated proliferation of MVEC. Direct administration of recombinant SPRY2
      protein has no effect on MVEC proliferation. However, SPRY2 protein binds the
      intracellular adaptor protein GRB2, indicating an intracellular localization. A
      SPRY2/GFP fusion protein remains in the cell, further supporting the
      intracellular localization of SPRY2. So the intracellular protein SPRY2 is
      involved in the non-cell autonomous inhibitory effect indirectly, via regulating
      the secretion of an inhibitor of FGF2 signalling in vertebrates, the evidence of
      which is presented here for the first time.

PMID- 10940628
TI  - Identification by differential display of a chicken tolloid-related
      metalloprotease specifically expressed in the caudal notochord.
AB  - While the ventralizing factor Sonic hedgehog is expressed in the entire notochord
      (Development 121 (1995) 2537) the latter displays distinct ventralizing
      activities along its rostrocaudal axis. Hence, in HH stage-10 chicken embryo, the
      caudal notochord exhibits floor plate inducing capacities lost by rostral regions
      (Development 117 (1993) 205). Therefore, we hypothesize that the caudal notochord
      produces some cofactors which may contribute to its ventralizing properties. In
      order to identify such molecules we applied the differential display strategy and
      isolated a secreted Tolloid-related metalloprotease displaying a regionalized
      expression in the notochord.

PMID- 10940629
TI  - Phenoloxidase, a marker enzyme for differentiation of the neural ectoderm and the
      epidermal ectoderm during embryonic development of amphioxus Branchiostoma
      belcheri tsingtaunese.
AB  - The development of phenoloxidase during amphioxus embryogenesis was
      spectrophotometrically and histochemically studied for the first time in the
      present study. It was found that (1) PO activity initially appeared in the
      general ectoderm including the neural ectoderm and the epidermal ectoderm at the
      early neurula stage but not in the mesoderm or the endoderm, and (2) PO activity
      disappeared in the neural plate cells but remained unchanged in the epidermal
      cells when the neural plate was morphologically quite distinct from the rest of
      the ectoderm. It is apparent that PO could serve as a marker enzyme for
      differentiation of the neural ectoderm from the epidermal ectoderm during
      embryonic development of amphioxus.

PMID- 10940630
TI  - Expression of CD44 during early development of the chick embryo.
AB  - CD44, the major cell-surface receptor for hyaluronate, is expressed on many cell
      types to mediate different functions including cell activation, homing and
      adhesion. The early pattern of CD44 expression was determined in the avian embryo
      by using a specific monoclonal antibody in whole-mount and tissue sections. CD44
      was first expressed on cephalic neural fold cells and later on by subpopulations
      of pre-and migratory cranial neural crest cells. Trunk neural crest cells did not
      express CD44. At the 18-20 somite stage, CD44 expressing cells were also
      localized in the caudal region of the embryo, in the mesoderm of the remaining
      primitive streak and in the caudal ectoderm and above the secondary neural tube
      during the process of cavitation. In addition, some hemopoietic cells present in
      the blood stream were also CD44 positive.

PMID- 10940631
TI  - Identification and expression of mouse netrin-4.
AB  - Netrins are secreted proteins that serve as potent axon guidance molecules in
      vertebrates and invertebrates. We report the identification of a novel mammalian
      member of this family. Netrin-4 is similar in predicted size and secondary
      structure to the other three netrins; all contain, in order, an amino-terminal
      signal sequence, a laminin-type globular domain of the 'VI' type, three laminin
      type epidermal growth factor (EGF) repeats, and a carboxyl-terminal 'netrin
      module'. In terms of primary sequence, however, netrin-4 is a distant relative of
      netrins-1-3, and its globular domain is more closely related to those of laminins
      than to those of other netrins. Netrin-4 is broadly expressed in both neural and
      non-neural tissues of embryonic and adult mice. In embryonic spinal cord, it is
      selectively expressed by cells at the lateral margins of the floor plate. In
      postnatal brain, it is selectively expressed in subsets of neurons, including
      cerebellar granule and hippocampal pyramidal cells.

PMID- 10940632
TI  - Expression of Cdcrel-1 (Pnutl1), a gene frequently deleted in velo-cardio-facial
      syndrome/DiGeorge syndrome.
AB  - The murine Cdcrel-1 (Pnutl1) gene belongs to the family of septins, which are
      thought to be involved in cytokinesis in yeast, Drosophila and vertebrates.
      Recent studies implicate Cdcrel-1 in the regulation of vesicle transport in
      neurons of the adult brain. The human homologue, hCDCREL-1 maps to chromosome
      22q11.2, a region commonly deleted in patients displaying velo-cardio-facial
      syndrome (VCFS) or DiGeorge syndrome (DGS). During development, Cdcrel-1
      transcripts are expressed from E10.5 on in the nervous system such as the dorsal
      root ganglia and the cranial ganglia as well as the lateral layer of the neural
      tube, the area where terminally differentiated neurons are located. Low level
      expression is found in the mesenchyme of the frontonasal mass and the limb bud
      mesenchyme of E11.5 and E13.5 murine embryos. At E15.5, expression is detected in
      the nervous tissue and in the neural layer of the eye. Based on the expression
      pattern as well as clinical data, Cdcrel-1 may be involved in the etiology of
      VCFS/DGS.

PMID- 10940634
TI  - The biphasic expression of IMP/Vg1-RBP is conserved between vertebrates and
      Drosophila.
AB  - The human IGF-II mRNA-binding proteins (IMPs) 1-3, and their Xenopus homologue
      Vg1 RNA-binding protein (Vg1-RBP) are RNA-binding proteins implicated in mRNA
      localization and translational control in vertebrate development. We have
      sequenced the Drosophila homologue (dIMP) of these genes, and examined its
      expression pattern in Drosophila embryos by in situ hybridization. The study
      shows that dIMP exhibits a biphasic expression pattern. In the early stages of
      development, a maternal pool of dIMP mRNA is evenly distributed in the embryo and
      degraded by the end of stage 4. Expression reappears in the developing central
      nervous system, where dIMP is expressed throughout neurogenesis. In addition,
      dIMP is present in the pole cells.

PMID- 10940633
TI  - Regional gene expression in the epithelia of the Xenopus tadpole gut.
AB  - In recent years much progress has been made in the understanding of the genes and
      mechanisms involved in specification of the cells of the endoderm, which give
      rise to the epithelium of the gut and respiratory system. However, little is
      known about the way in which the gut becomes patterned along its anterior
      posterior axis, that is, how boundaries are established between the different
      epithelia of the gut tube. Here we show that the expression patterns of five
      genes divide the Xenopus tadpole gut epithelium into at least four regions along
      this axis in the undifferentiated, 3-day-old gut (stage 41), and that these
      divisions are maintained until at least 7 days, when cell differentiation is well
      under way. In addition, the restricted expression patterns of these genes clearly
      mark the anterior and posterior boundaries of the intestine. Xsox2 is expressed
      in the anterior gut, spanning the oesophagus and stomach but terminating at the
      stomach/intestine boundary. Xcad1 and Xcad2, two caudal-type homeobox genes, are
      expressed in a region with an anterior limit at this boundary and a posterior
      limit between the colon and proctodeum, therefore covering the whole of the small
      and large intestines. Intestinal fatty acid binding protein (IFABP) is expressed
      only in the anterior small intestine, and the even-skipped homeobox gene Xhox3 is
      expressed in the most posterior part of the gut, the proctodeum.

PMID- 10940635
TI  - The novel gene glaikit, is expressed during neurogenesis in the Drosophila
      melanogaster embryo.
AB  - A novel gene glaikit (gkt) has been identified which is expressed in the
      delaminating neuroblasts of the D. melanogaster embryonic central nervous system.
      At the earliest stages of embryonic development the expression of glaikit was
      ubiquitous, but by the time the neuroblasts are delaminating gkt expression
      became restricted to neuroblasts and a few ganglion mother cells. The gkt gene
      has no characterized homologues and encodes no previously described protein
      motifs. There are, however, evolutionary conserved predicted genes present in S.
      pombe, S. cerevisiae and C. elegans. Ectopic neuroblasts induced in either Notch
      or Delta mutant backgrounds also showed expression of glaikit.

PMID- 10940636
TI  - Tbx12, a novel T-box gene, is expressed during early stages of heart and retinal
      development.
AB  - T-box genes encode transcription factors that regulate many developmental
      processes. We have cloned a novel mouse T-box gene, Tbx12. Tbx12 is the
      vertebrate homologue of the Drosophila H15 gene and the Caenorhabditis elegans
      tbx-12 gene. Tbx12 is expressed in extraembryonic tissues such as the amnion and
      allantois. In the embryo, Tbx12 is strongly expressed in the neural retina and
      the heart.

PMID- 10940637
TI  - Homeobrain, a novel paired-like homeobox gene is expressed in the Drosophila
      brain.
AB  - The homeobrain (hbn) gene is a new paired-like homeobox gene which is expressed
      in the embryonic brain and the ventral nerve cord. Expression of homeobrain
      initiates during the blastoderm stage in the anterior dorsal head primordia and
      the gene is persistently expressed in these cells which form parts of the brain
      during later embryonic stages. An additional weaker expression pattern is
      detected in cells of the ventral nerve cord from stage 11 on. The homeodomain in
      the Homeobrain protein is most similar to the Drosophila proteins DRx, Aristaless
      and Munster. In addition, the localized brain expression patterns of homeobrain
      and DRx resemble each other. Two other homeobox genes, orthopedia and DRx are
      clustered in the 57B region along with homeobrain. The current evidence indicates
      that homeobrain, DRx and orthopedia form a homeobox gene cluster in which all the
      members are expressed in specific embryonic brain subregions.

PMID- 10940638
TI  - Biochemistry, physiology and pathophysiology of the extracellular calcium-sensing
      receptor.
AB  - Calcium (Ca(2+)) has long been recognized as a physiologically indispensable ion
      owing to its numerous intra- and extracellular roles. More recently, it has
      become apparent that extracellular calcium (Ca(2+)(o)) also serves as an
      extracellular first messenger following the cloning of a Ca(2+)(o)-sensing
      receptor (CaR) that belongs to the superfamily of G protein-coupled receptors
      (GPCR). The CaR probably functions as a dimer in performing its central role of
      "sensing" minute alterations in Ca(2+)(o) and adjusting the secretion of
      parathyroid hormone (PTH) so as to normalize Ca(2+)(o) through the actions of PTH
      on the effector elements of the mineral ion homeostatic system (e.g., kidney,
      bone and intestine). Several inherited human conditions are caused by
      inactivating or activating mutations of this receptor, and mice have been
      generated with targeted disruption of the CaR gene. Characteristic changes in the
      functions of parathyroid and kidney in patients with these conditions and in CaR
      deficient mice have proven the physiological importance of the CaR in mineral ion
      homeostasis. An accumulating body of evidence, however, suggests that the CaR
      also plays numerous roles outside the realm of systemic mineral ion homeostasis.
      The receptor regulates processes such as cellular proliferation and
      differentiation, secretion, membrane polarization and apoptosis in a variety of
      tissues/cells. Finally, the availability of specific "calcimimetic", allosteric
      CaR activators - which are currently in clinical trials - will probably have
      therapeutic implications for diseases caused by malfunction of the CaR in tissues
      not only within, but also outside, the mineral ion homeostatic system.

PMID- 10940639
TI  - Structure-function and biological role of betacellulin.
AB  - Betacellulin (BTC) belongs to the epidermal growth factor (EGF) family of peptide
      ligands that are characterised by a six-cysteine consensus motif that forms three
      intra-molecular disulfide bonds crucial for binding the ErbB receptor family. BTC
      was initially described, purified and cloned from a mouse insulinoma cell line.
      BTC is proteolytically processed from a larger membrane-anchored precursor and is
      a potent mitogen for a wide variety of cell types. BTC binds and activates ErbB-1
      and ErbB-4 homodimers and is further characterised by its unique ability to
      activate all possible heterodimeric ErbB receptors. BTC is widely expressed in
      most tissues and various body fluids, including milk. Expression is particularly
      high in the pancreas where it is thought to play a role in the differentiation of
      pancreatic beta cells. While much is known about the ErbB receptor binding
      characteristics of BTC and its effect on a variety of cultured cells under
      different conditions, the challenge that lies ahead is to determine the role of
      BTC in vivo. This review will focus on the structure of BTC and the various
      biological effects ascribed to this member of the EGF family.

PMID- 10940640
TI  - Genetic analysis of homologous DNA recombination in vertebrate somatic cells.
AB  - The maintenance of genomic stability and the ability to repair induced DNA damage
      in vertebrate cells require homologues of the yeast RAD52 epistasis group genes.
      The homologous recombination carried out by the products of these genes is
      essential and appears to be closely linked to DNA replication. Defects in
      recombination and associated activities are implicated in human cancer. This
      review summarises recent biochemical and genetic findings on the roles played by
      the vertebrate RAD52 group gene products in recombination. We describe the
      phenotypic analysis of genetically engineered mammalian and chicken mutants of
      homologous recombination genes.

PMID- 10940641
TI  - Cytokines in airway inflammation.
AB  - With over 50 potential asthma mediators, cytokines are the latest group of
      substances which have been investigated for their potential role in this disease.
      The use of murine models of allergic inflammation has facilitated the
      investigation of the role of individual cytokines in this response. The use of
      targeted gene disruption, overexpression of genes and monoclonal antibodies
      directed against cytokines have allowed a detailed examination of the role
      cytokines play in IgE production, eosinophil recruitment and bronchial
      hyperresponsiveness, which are the characteristic features of the asthma
      phenotype. Despite the introduction of this new methodology, conflicting reports
      relating to the role of cytokines in allergic inflammation, highlight the
      complexity of allergic inflammation and challenge the notion that a single
      cytokine can explain the asthma phenotype.

PMID- 10940642
TI  - Evidence for the existence of two soluble NAD(+) kinase isoenzymes in Euglena
      gracilis Z.
AB  - Two soluble NAD(+) kinase isoenzymes (isoenzymes 1 and 2) from Euglena gracilis
      were separated by preparative electrophoresis and characterized. They display
      several similar properties: both have an identical apparent molecular weight of
      68 kDa and their activities are independent on calmodulin, insensitive to 2
      mercaptoethanol but inhibited by p-chloromercurybenzoate, 5, 5'-dithiobis(2
      nitrobenzoate) and, surprisingly, by low dithiothreitol concentrations, the
      inhibition by dithiothreitol being irreversible for isoenzyme 1 but reversible
      for isoenzyme 2. Nevertheless, the two isoenzymes mainly differ by their
      specificities towards triphosphate nucleotides and their catalytic mechanisms.
      Isoenzyme 1 is as active in the presence of ATP as of GTP and acts by a ping-pong
      mechanism with a k(M) for NAD(+) of 0.26 mM and a k(M) for low MgATP(2
      )concentrations of 0.03 mM. Isoenzyme 2 is three-fold more active in the presence
      of GTP than of ATP and operates by a sequential mechanism with k(M)s for NAD(+)
      and MgGTP(2-) of 1.03 and 0.20 mM, respectively. This study shows the evidence
      for the existence of two structurally similar but catalytically different NAD(+)
      kinase isoenzymes in E. gracilis. One resembles the enzyme previously described
      in bacteria. The other displays a catalytic mechanism identical to that of NAD(+)
      kinase from other organisms but remains unique among all the NAD(+) kinases
      studied to-date regarding its specificity towards GTP.

PMID- 10940643
TI  - Inhibition kinetics of green crab (Scylla serrata) alkaline phosphatase activity
      by dithiothreitol or 2-mercaptoethanol.
AB  - Green crab (Scylla serrata) alkaline phosphatase (EC 3.1.3.1) is a metalloenzyme
      which catalyzes the nonspecific hydrolysis of phosphate monoesters. Some
      pollutants in seawater affect the enzyme activity causing loss of the biological
      function of the enzyme, which affects the exuviating crab-shell and threatens the
      survival of the animal. The present paper studies the effects of thiohydroxyal
      compounds on the activity of green crab alkaline phosphatase. The results show
      that thiohydroxyal compounds can lead to reversible inhibition. The equilibrium
      constants have been determined for dithiothreitol (DTT) and mercaptoethanol (ME)
      binding with the enzyme and/or the enzyme-substrate complexes. The results show
      that both DTT and ME are non-competitive inhibitors. The kinetics of enzyme
      inactivation by ME at low concentrations has been studied using the kinetic
      method of the substrate reaction. The results suggest that at pH 10.0, the action
      of ME on green crab ALP is first quick equilibrium binding and then slow
      inactivation. The microscopic rate constants were determined for inactivation and
      reactivation. The rate constant of the forward inactivation (k(+0)) is much
      larger than that of the reverse reactivation (k(-0)). Therefore, when the ME
      concentration is sufficiently large, the enzyme is completely inactivated.

PMID- 10940644
TI  - Comparison of inactivation and unfolding of methanol dehydrogenase during
      denaturation in guanidine hydrochloride and urea.
AB  - The activity and the conformational changes of methanol dehydrogenase (MDH), a
      quinoprotein containing pyrrolo-quinoline quinone as its prosthetic group, have
      been studied during denaturation in guanidine hydrochloride (GdnHCl) and urea.
      The unfolding of MDH was followed using the steady-state and time resolved
      fluorescence methods. Increasing the denaturant concentration in the denatured
      system significantly enhanced the inactivation and unfolding of MDH. The enzyme
      was completely inactivated at 1 M GdnHCl or 6 M urea. The fluorescence emission
      maximum of the native enzyme was at 332 nm. With increasing denaturant
      concentrations, the fluorescence emission maximum red-shifted in magnitude to a
      maximum value (355 nm) at 5 M GdnHCl or 8 M urea. Comparison of inactivation and
      conformational changes during denaturation showed that in general accord with the
      suggestion made previously by Tsou, the active sites of MDH are situated in a
      region more flexible than the molecule as a whole.

PMID- 10940645
TI  - Effect of metal ions on the activity of green crab (Scylla serrata) alkaline
      phosphatase.
AB  - Green crab (Scylla serrata) alkaline phosphatase (EC 3.1.3.1) is a metalloenzyme,
      which catalyzes the nonspecific hydrolysis of phosphate monoesters. The present
      paper deals with the study of the effect of some kinds of metal ions on the
      enzyme. The positive monovalent alkali metal ions (Li(+), Na(+) and K(+)) have no
      effect on the enzyme; positive bivalent alkaline-earth metal ions (Mg(2+), Ca(2+)
      and Ba(2+)) and transition metal ions (Mn(2+), Co(2+), Ni(2+) and Cd(2+))
      activate the enzyme; heavy metal ions (Hg(2+), Ag(+), Bi(2+), Cu(2+) and Zn(2+))
      inhibit the enzyme. The activation of magnesium ion on the enzyme appears to be a
      partial noncompetitive type. The kinetic model has been set up and a new plot to
      determine the activation constant of Mg(2+) was put forward. From the plot, we
      can easily determine the activation constant (K(a)) value and the activation
      ratio of Mg(2+) on the enzyme. The inhibition effects of Cu(2+) and Hg(2+) on the
      enzyme are of noncompetitive type. The inhibition constants have been determined.
      The inhibition effect of Hg(2+) is stronger than that of Cu(2+).

PMID- 10940646
TI  - Conformational changes and inactivation of calf intestinal alkaline phosphatase
      in trifluoroethanol solutions.
AB  - The changes in activity and unfolding of calf intestinal alkaline phosphatase
      (CIP) during denaturation in different concentrations of trifluoroethanol (TFE)
      have been investigated by far-ultraviolet circular dichroism and fluorescence
      emission spectra. Unfolding and activation rate constants were measured and
      compared, the activation and inactivation courses were much faster than that of
      unfolding, which suggests that the active site of CIP containing two zinc ions
      and one magnesium ion is situated in a limited and flexible region of the enzyme
      molecule that is more fragile to the denaturant than the protein as a whole.
      However, compared to other metalloenzymes, CIP is inactivated at higher
      concentrations of TFE as denaturant.

PMID- 10940647
TI  - Metallothionein isoform expression by breast cancer cells.
AB  - Expression of metallothionein (MT) isoforms by a human breast cancer cell line,
      PMC42, which retains many characteristics of normal breast epithelial cells and
      expresses functional estrogen receptors, was examined because it has been
      proposed that human breast cancer cells which are estrogen receptor positive can
      be differentiated from those which are estrogen receptor negative, by failure to
      express MT-1E [J.A. Friedline, S.H. Garrett, S. Somji, J.H. Todd, D. A. Sens,
      Differential expression of the MT-1E gene in estrogen-receptor positive and 
      negative breast cancer cell lines, Am. J. Pathol. 152 (1998) 23-27]. Using RT
      PCR, PMC42 cells were found to transcribe genes for the MT isoforms IE, IX and 2A
      but not 1A or 1H. In order to examine which of the expressed isoforms might
      protect against metal toxicity, the cells were challenged with high
      concentrations of zinc and copper. Using competitive RT-PCR, cells resistant to
      500 microM zinc showed 7+/-2 fold (SD, n=3) increases in expression of MT-1X and
      6+/-3 fold increases in expression of MT-2A compared to control cells in normal
      media. For cells resistant to 250 microM copper the corresponding increases were
      37+/-13 and 60+/-20 fold, whilst for control cells treated with 250 microM copper
      for only 6 h, increases were 10+/-3 and 6+/-3 fold. There was only a low level of
      expression of MT-1E in untreated cells and but a >120 fold increase in copper-
      resistant cells. Thus estrogen receptor positive cells cannot, in general, be
      differentiated from estrogen receptor negative cells by failure to express MT-1E,
      as suggested by Friedline et al. (1998). Increased expression of MT-1E, as well
      as MT-1X and MT-2A, protects against metal toxicity in PMC42 breast cancer cells.

PMID- 10940649
TI  - An endogenous proteinacious inhibitor in porcine liver for S-adenosyl-L
      methionine dependent methylation reactions: identification as oligosaccharide
      linked acyl carrier protein.

PMID- 10940648
TI  - Neonatal STZ model of type II diabetes mellitus in the Fischer 344 rat:
      characteristics and assessment of the status of the hepatic adrenergic receptors.
AB  - The Fischer 344 rat was found to be extremely sensitive to the diabetogenic
      effects of neonatally injected streptozotocin (STZ): injection of 40-100 mg/kg
      STZ at 1.5 days postnatal produced in the adult graded levels of hyperglycemia in
      males but not the females. The optimal dose in the 1.5 day old male was 80 mg/kg:
      it produced hyperglycemia without affecting growth or thyroid status in the
      adult. The neonatally STZ-injected adult rat displayed characteristics consistent
      with type II diabetes: mild hyperglycemia accentuated by fasting or consumption
      of a high fat diet; little change in insulin levels; slight elevation in glucagon
      levels; no alterations in ketones. Using radioligand binding techniques to
      isolated rat liver plasma membranes, compared to the control state, the type II
      diabetic state was found to have: no effect on either alpha(2)- or beta
      adrenergic receptor binding; a decrease in the major dominant alpha(1)-adrenergic
      receptor, reflecting a decrease in receptor numbers but not their affinity; an
      increase in the plasma membrane calcium transport system, potentially depleting
      intracellular calcium stores essential for producing an alpha(1)-adrenergic
      receptor response. Since the alpha(1)-adrenergic receptor-calcium effector system
      is critical for the actions of catecholamines in the rat, these results suggest
      that the liver in the type II diabetic state may be refractory to the actions of
      catecholamines. We propose that the diabetes-evoked decrease in the dominant
      adrenergic receptor-effector system through which catecholamines act may be the
      cellular expression of defective glucocounterregulation in the diabetic state.

PMID- 10940650
TI  - Gene rearrangements in bone marrow cells of patients with acute myelogenous
      leukemia.
AB  - At diagnosis, clonal gene rearrangement probes [retinoic acid receptor (RAR)
      alpha, major breakpoint cluster region (M-bcr), immunoglobulin (Ig)-JH, T cell
      receptor (TcR)-beta, myeloid lymphoid leukemia (MLL) or cytokine genes (GM-CSF, G
      CSF, IL-3)] were detected in bone marrow samples from 71 of 153 patients with
      acute myelogenous leukemia (AML) (46%): in 41 patients with primary AML (pAML)
      (58%) and in 30 patients with secondary AML (42%). In all cases with
      promyelocytic leukemia (AML-M3) RAR-alpha gene rearrangements were detected (n =
      9). Gene rearrangements in the Ig-JH or the TcR-beta or GM-CSF or IL-3 or MLL
      gene were detected in 12, 10, 16 and 12% of the cases, respectively, whereas only
      few cases showed gene rearrangements in the M-bcr (6%) or G-CSF gene (3%).
      Survival of pAML patients with TcR-beta gene rearrangements was longer and
      survival of pAML patients with IL-3 or GM-CSF gene rearrangement was shorter than
      in patients without those rearrangements. No worse survival outcome was seen in
      patients with rearrangements in the MLL, Ig-JH or M-bcr gene. In remission of AML
      (CR), clonal gene rearrangements were detected in 23 of 48 cases (48%) if samples
      were taken once in CR, in 23 of 26 cases (88%) if samples were taken twice in CR
      and in 23 of 23 cases (100%) if samples were studied three times in CR. All cases
      with gene rearrangements at diagnosis showed the same kind of rearrangement at
      relapse of the disease (n = 12). Our data show that (1) populations with clonal
      gene rearrangements can be regularly detected at diagnosis, in CR and at relapse
      of AML. (2) Certain gene rearrangements that are detectable at diagnosis have a
      prognostic significance for the patients' outcome. Our results point out the
      significance of gene rearrangement analyses at diagnosis of AML in order to
      identify 'poor risk' patients - independently of the karyotype. Moreover, the
      persistence of clonal cells in the further course of AML can be studied by gene
      rearrangement analysis.

PMID- 10940651
TI  - p53 pathway in apoptosis induced by all-trans-retinoic acid in acute myeloblastic
      leukaemia cells.
AB  - The role of the p53 pathway in apoptosis induced by all-trans-retinoic acid
      (ATRA) was studied in 5 human acute myeloid leukaemia (AML) cell lines, OU-AML-3,
      -4, -5, -7 and -8, previously established and characterized by the authors.
      Although all the cell lines have a wild-type (wt) p53 gene, the protein is in a
      mutant conformation detectable by the anti-p53 antibody PAb 240. Exposure of the
      cell lines to 1.0 microM ATRA for 72 h caused induction of apoptosis detectable
      by morphology and the annexin V assay. The number of apoptotic cells according to
      the annexin V assay varied from 16 +/- 8% (OU-AML-7) to 61 +/- 4% (OU-AML-3) in
      ATRA-treated cells, while it was 7 +/- 6% in control cells. Western blotting and
      flow cytometry showed down-regulation of the p53 protein by ATRA. The
      conformation of p53 remained unchanged, being detectable in flow cytometry by PAb
      240, but not by PAb 1620 (an antibody which only detects p53 in wt conformation).
      At the same time bcl-2 was down-regulated as shown by Western blotting and flow
      cytometry, while no induction of bax was observed by ATRA. On the basis of these
      results, ATRA-induced apoptosis in these AML cell lines is independent of the p53
      pathway, although it is associated with the down-regulation of bcl-2.

PMID- 10940652
TI  - Down-regulation of CD98 in melphalan-resistant myeloma cells with reduced drug
      uptake.
AB  - Although melphalan has been used as a therapeutic reagent for multiple myeloma,
      many patients become refractory. To elucidate the mechanism of resistance to
      melphalan, we generated a melphalan-resistant myeloma cell line, KHM-11(EMS), by
      treating a parental line, KHM-11, with a mutagen, ethylmethanesulfonate. KHM
      11(EMS) is 55 times more resistant to melphalan. gamma-Glutamylcysteine
      synthetase, P-glycoprotein, multidrug-resistance-associated protein, lung
      resistance-related protein and the Bcl-2 family of proteins were not responsible
      for the drug resistance in KHM-11(EMS). Intracellular incorporation of melphalan
      to myeloma cells was determined by using [(14)C]-labeled melphalan. Accumulation
      of melphalan in KHM-11(EMS) was 43% of KHM-11, while the efflux rates were
      comparable in both cell lines. The uptake of melphalan was inhibited by the
      addition of L-phenylalanine, indicating that melphalan is incorporated through
      the L-phenylalanine transporter as reported previously. Expression of CD98, which
      was recently cloned as an L-phenylalanine transporter, was 6-fold decreased in
      KHM-11(EMS), suggesting that CD98 may be correlated with the incorporation of
      melphalan. CD98 expression and incorporation of melphalan were analyzed in fresh
      purified myeloma cells from 5 patients. All myeloma cells from 4 cases expressed
      CD98 at a high level and incorporated melphalan. However, tumor cells from 1 case
      expressed CD98 at low levels and did not incorporate melphalan. Taken together,
      reduced melphalan uptake could be responsible for the drug resistance in KHM
      11(EMS), and down-regulation of CD98 may be related to this phenomenon. Further
      investigation of the correlation between impaired drug uptake and down-regulation
      of CD98 in myeloma cells should be important to understand the mechanism of
      resistance to melphalan.

PMID- 10940653
TI  - Thrombopoietic cytokines in patients with iron deficiency anemia with or without
      thrombocytosis.
AB  - Iron deficiency anemia is a cause of reactive thrombocytosis. A moderate increase
      in platelet numbers is common but sometimes counts may exceed 1,000 x 10(9)/l.
      The mechanisms causing reactive thrombocytosis are unclear. In this study, we
      evaluated 15 women with iron deficiency anemia and thrombocytosis (platelets >450
      x 10(9)/l) and 16 women with iron deficiency anemia with normal platelet counts.
      Serum samples were taken before oral iron replacement therapy, after 1 and 3
      months and at the end of replacement therapy. Thrombopoietin, erythropoietin
      (EPO), leukemia inhibitory factor, interleukin-6 and interleukin-11 levels were
      assayed. There was no change in the levels of thrombopoietic cytokines except for
      EPO. The correlation between high EPO levels and high platelet counts may suggest
      that EPO increases platelet counts, but the same EPO level changes can also be
      demonstrated in women with iron deficiency anemia but normal initial platelet
      counts. The fact that the levels of other cytokines remained unchanged during
      treatment suggests that either these cytokines have no effect on reactive
      thrombocytosis or the change in platelet counts in our patients is in a narrow
      range and is thus not affected by the cytokine levels.

PMID- 10940654
TI  - Estimation of stem cell fractions in peripheral blood stem cell harvest by using
      an SE-9000 hematology analyzer.
AB  - We inquired whether stem cell fractions in peripheral blood stem cell harvest
      could be precisely detected by using a hematopoietic progenitor cell (HPC)
      counting system applied to an automated hematology analyzer, SE-9000. Although
      there was an apparent increase in the HPCs 20 h after storage in nondiluted
      conditions, samples diluted with RPMI-1640 containing 1.0 mg/ml EDTA-2K showed a
      relatively stable number of HPCs. There was a significant relationship between
      HPCs and CD34 cells (n = 75, r = 0.769). This method may represent the least
      expensive and most time-effective way for stem cell estimation in harvest
      products.

PMID- 10940655
TI  - Human IL-18 bioactivity in hematological malignancies with highly elevated serum
      IL-18 levels.

PMID- 10940656
TI  - Clinical significance of simultaneous determination of serum soluble transferrin
      receptor, soluble Fas, soluble Fas ligand, hepatocyte growth factor and
      interleukin 18 levels in a patient with hemophagocytic syndrome.

PMID- 10940657
TI  - Induction of apoptosis in B lymphoma cells by activation with CD40L.

PMID- 10940658
TI  - Increased general predisposition to cancer but not to specific neoplasms of the
      hematopoietic system in children with hematological neoplasms: a hypothesis.

PMID- 10940659
TI  - Clinically significant inhibitors in hemophilia A patients from India tend to
      persist.

PMID- 10940660
TI  - Visual system in a diurnal marsupial, the numbat (Myrmecobius fasciatus): retinal
      organization, visual acuity and visual fields.
AB  - The visual system of the numbat (Myrmecobius fasciatus), a highly endangered
      diurnal marsupial, has been investigated both anatomically and behaviorally. The
      ganglion cell layer, examined in cresyl-violet stained wholemounts, contained
      832,800 ganglion cells; the number of ganglion cells corresponded to optic axon
      counts. An area centralis was located in the mid-temporal retina, where cells
      formed a bilayer, but there was no evidence of a visual streak. Visual acuity,
      estimated from counts of peak ganglion cell density (8,100/mm(2)) and
      measurements of posterior nodal distance (7.84 mm), was found to be 6.3 cycles
      per degree. The value was similar to that of 5.2 cycles per degree estimated by
      behavioral tests. Sectioned material revealed the presence of numerous oil
      droplets in a cone-dominated retina. A rich retinal vasculature of the end-artery
      type of paired arteries and veins formed beds in the ganglion cell and inner
      nuclear layers. Measurements of visual fields revealed a binocular overlap of 80
      degrees in the horizontal plane, and a total field of view approaching 240
      degrees of visual angle. Monitoring of pupillary responses with an infrared video
      camera showed that the numbat possesses a remarkably wide, static pupil. Our
      results are discussed in relation to the ecology of the species and its
      phylogeny.

PMID- 10940662
TI  - Retinal ganglion cell topography in elasmobranchs.
AB  - Retinal wholemounts are used to examine the topographic distribution of retinal
      cells within the ganglion cell layer in a range of elasmobranchs from different
      depths. The retina is examined for regional specializations for acute vision in
      six species of selachians, Galeocerdo cuvieri, Hemiscyllium ocellatum,
      Scyliorhinus canicula, Galeus melastomus, Etmopterus spinax, Isistius
      brasiliensis, one species of batoid, Raja bigelowi and one species of chimaera,
      Hydrolagus mirabilis. These species represent a range of lifestyles including
      pelagic, mesopelagic and benthic habitats, living from shallow water to the sea
      bottom at a depth of more than 3000 m. The topography of cells within the
      ganglion cell layer is non-uniform and changes markedly across the retina. Most
      species possess an increased density of cells across the horizontal (dorsal)
      meridian or visual streak, with a density range of 500 to 2,500 cells per mm(2)
      with one or more regional increases in density lying within this specialized
      horizontal area. It is proposed that the higher spatial resolving power provided
      by the horizontal streak in these species mediates panoramic vision in the lower
      frontal visual field. Only I. brasiliensis possesses a concentric arrangement of
      retinal iso-density contours in temporal retina or an area centralis, thereby
      increasing spatial resolving power in a more specialized part of the visual
      field, an adaptation for its unusual feeding behavior. In Nissl-stained material,
      amacrine and ganglion cell populations could be distinguished on the criteria of
      soma size, soma shape and nuclear staining. Quantitative analyses show that the
      proportion of amacrine cells lying within the ganglion cell layer is non-uniform
      and ranges between 0.4 and 12.3% in specialized retinal areas and between 8.2 and
      48.1% in the peripheral non-specialized regions. Analyses of soma area of the
      total population of cells in the ganglion cell layer also show that the pelagic
      species possess significantly smaller soma (9-186 micrometer(2)) than benthic
      and/or deep-sea species (16-338 micrometer(2)), and that a number of different
      morphological classes of cells are present including a small population of giant
      ganglion cells.

PMID- 10940661
TI  - Variability in the location of the retinal ganglion cell area centralis is
      correlated with ontogenetic changes in feeding behavior in the black bream,
      Acanthopagrus butcheri (Sparidae, teleostei).
AB  - The development of neural cell topography in the retinal ganglion cell layer was
      examined in a teleost, the black bream (Acanthopagrus butcheri). From Nissl
      stained wholemounts, it was established that fish between 10 and 15 mm standard
      body length (SL) possess high cell densities throughout the dorso-temporal
      retinal quadrant, with peak cell densities located in temporal regions of the
      retina. However, in fish between 15 and 80 mm SL, a wide variation in the
      position of the peak cell density is revealed with the locations of the areae
      centrales (AC) ranging from exclusively temporal to periphero-dorsal retina. Fish
      larger than 80 mm SL always possess an AC located in the dorsal region of the
      dorso-temporal retinal quadrant. The topography of ganglion cells within the
      ganglion cell layer was determined by comparing the numbers of ganglion cells
      retrogradely-labeled from the optic nerve with the total population of Nissl
      stained neurons (ganglion plus displaced amacrine cells) in a range of different
      sized individuals. Ganglion cell topography was the same as that recorded for all
      Nissl-stained neurons. The feeding behavior of juveniles from metamorphosis to 80
      mm SL was observed, where fish were given the choice of feeding on live food in
      mid-water (until 15 mm SL) or obtaining pellets from the surface or the bottom. A
      range of feeding patterns was recorded, with the smallest fish taking food from
      mid-water but individuals between 15 and 80 mm SL taking food either from the
      surface or the bottom or both. A correlation between the preferred mode of
      feeding and the position of the AC was found, such that those individuals feeding
      in mid-water or at the surface possess a temporal or intermediate (dorso-
      temporal) AC, whereas those predominantly feeding from the bottom possess a
      dorsal AC.

PMID- 10940664
TI  - Regional variation in receptive field properties of tectal neurons in pigeons.
AB  - The present study provides the first electrophysiological evidence for
      dorsoventral variation in the receptive field properties of tectal cells in
      pigeons. According to their receptive field organization, visual response
      properties and laminar locations, 95 tectal neurons recorded in the present study
      could be categorized into two groups: (1) Fifty-five DL-neurons were recorded in
      the dorsal, dorso-lateral, lateral and ventro-lateral tectum and characterized by
      an excitatory receptive field surrounded by an inhibitory receptive field. Most
      of them almost equally responded to white and black objects, but did not respond
      to switch-on and -off of a light spot. (2) Forty VC-neurons were recorded in the
      ventral tectum and characterized by an excitatory receptive field alone. Their
      responses to switch-on of a light spot and to a white object were significantly
      stronger than those to light-off and to a black object, respectively. DL-neurons
      preferred higher velocity, whereas VC-neurons preferred lower velocity. The
      recording sites of 53 of 95 cells (56%) examined were marked with pontamine sky
      blue, showing that DL-neurons were located in tectal layers I-IV, predominantly
      in layer II, whereas VC-neurons were mainly concentrated in sublayer IIc. The
      receptive fields of VC-neurons were located within the rostroventral visual field
      possibly corresponding to the red field of the pigeon retina, suggesting that
      they might be associated with visual food-foraging behaviors.

PMID- 10940663
TI  - Visual system labeled by c-Fos immunohistochemistry after light exposure in the
      'blind' subterranean zambian mole-rat (Cryptomys anselli).
AB  - The Zambian mole-rat (Cryptomys anselli) is a rodent that lives and forages
      underground, and under natural conditions is rarely, if ever, exposed to light.
      Its eye is organized as in other rodents and is prominent but minuscule. The
      animals do not seem to react to light behaviorally or to orient visually,
      although exact physiological and/or behavioral experiments have not been
      conducted to date. Nuclear expression of transcriptional regulatory protein (c
      Fos) as a marker of cell activity was studied immunohistochemically in five mole
      rats exposed to bright light for 1 h after 3 days in constant darkness, and in
      four non-stimulated control animals that were kept in darkness for three days and
      then killed under deep anesthesia. The retinae and retino-recipient areas of non
      stimulated animals remained unlabeled, but many of these structures showed strong
      c-Fos expression bilaterally [retina, dorsal lateral geniculate body (DLG),
      olivary pretectal nucleus, retrosplenial cortex, neocortex] in light-exposed
      animals. In contrast, the suprachiasmatic nucleus did not seem to be affected by
      light stimuli during the experiment. In both light-stimulated and control animals
      the rudimentary superior colliculus exhibited slight immunoreactivity.
      Interestingly, the olivary pretectal nucleus, which in mammals is involved in
      light/dark discrimination, as well as the DLG as part of the image-forming visual
      system were consistently labeled by c-Fos after light stimulation, indicating
      that vision in Cryptomys possibly plays a more significant role than previously
      assumed.

PMID- 10940665
TI  - Organization of stroke care: education, stroke units and rehabilitation. European
      Stroke Initiative (EUSI).

PMID- 10940666
TI  - Risk factors and stroke prevention. European Stroke Initiative (EUSI).

PMID- 10940667
TI  - Acute treatment of ischemic stroke. European Stroke Initiative (EUSI).

PMID- 10940668
TI  - The mechanism of growth-promoting effects of prolactin in embryogenesis--links to
      growth factors.
AB  - The polypeptide hormone prolactin (PRL) has been implicated in the regulation of
      embryonic growth and development, but the control mechanisms involved in the
      effects of the hormone are poorly understood. Several investigators suggested
      that there may be a possible link between the effects of PRL and insulin-like
      growth factors (IGFs). Recent studies have also shown that ligand-induced
      activation of PRL receptors leads to tyrosine phosphorylation of multiple
      intracellular proteins, and tyrosine kinase activation takes place in mediating
      the mitogenic action of PRL. In order to determine whether IGFs are involved in
      mediating the growth-promoting effect of PRL, rat embryos were culture in vitro
      for 48 h in whole rat serum and serum depleted of low molecular weight molecules
      (30 kD retenate) supplemented with rat PRL in the presence and absence of
      antisera against rat PRL, IGF I and IGF II. To investigate the effects of
      inhibiting the signal transduction of the PRL receptors, the embryos were
      preincubated for 2 h in retenate in the presence of tyrosine kinase inhibitors,
      tyrphostin 47 and genistein, then rat PRL was added to the culture medium.
      Embryos cultured in retenate showed severe growth retardation, and the addition
      of rat PRL caused significant increase in growth and development of the embryos
      suggesting that embryos may be able to utilize maternally derived PRL during
      organogenesis. The presence of antiserum against rat PRL abolished the PRL
      induced increase in development and antibodies against IGF I and II had a similar
      effect, suggesting that IGFs may be involved in the effect of the hormone. The 2
      hour preincubation with genistein and tyrphostin also abolished the PRL-induced
      increase in development. These results indicate that functional PRL receptors are
      present in rat embryos at this stage which may play an important role in the
      control of growth and development and this may be linked to growth factors and
      their receptors.

PMID- 10940669
TI  - Gonadotropin-releasing hormone receptor mRNA expression in the ovaries of
      neonatal and adult rats.
AB  - Recent studies have shown that gonadotropin-releasing hormone (GnRH) can exert
      various effects on the rat ovary by acting through its specific receptors. To
      determine the cell types responsive to the action of GnRH under physiological
      conditions in the ovary, distribution of the GnRH receptor mRNA was studied
      histologically by in situ hybridization in neonatal and adult rats. Expression of
      the luteinizing hormone receptor mRNA was also examined to judge the growing
      state of follicles and the corpora lutea. In neonatal rat ovaries, no significant
      GnRH receptor mRNA signal was detected until 5 days after birth. The expression
      was first observed at 10 days in the interstitial cells. At 15 days of age, the
      receptor mRNA was expressed in the granulosa cells of most preantral and early
      antral follicles, while no hybridization signal was detected in oocyte and theca
      cells. In adult cycling rats, GnRH receptor mRNA was detected mainly in the
      granulosa cells of most follicles and luteal cells. The granulosa cells of
      atretic follicles showed a very high level of the mRNA expression throughout
      their degenerating process. A strong hybridization signal was also detected in
      the mural granulosa cells of mature follicles. Newly formed (developing) corpora
      lutea exhibited signals with moderate intensity in the luteal cells, and the
      older ones showed weaker signals. The finding that the initial expression of GnRH
      receptor mRNA was seen in the interstitial cells of neonatal ovaries implies an
      unknown function of the ovarian GnRH receptor in ovarian development. The high
      level expression of GnRH receptor mRNA in atretic and mature follicles supports
      the putative roles of GnRH in the induction of follicular atresia and ovulation
      in rat ovaries.

PMID- 10940670
TI  - Mast cells accumulate in rat bone marrow after ovariectomy.
AB  - We have previously shown that mast cells (MC) may act as accessory cells of bone
      resorption in a synchronized model of resorption. The aim of this study was to
      verify whether bone marrow MC accumulated during the phase of rapid osteopenia
      development in estrogen-deprived rats. Sprague-Dawley rats, 90 days old, were
      subjected to bilateral ovariectomy (OVX) or sham surgery (controls). Bone
      histomorphometry was performed in the proximal tibia metaphysis. Thirty days
      after surgery, serum estradiol had dropped (p < 0.002), and osteopenia was well
      established in the OVX rats (trabecular bone volume decreased by 69%, p <
      0.0001). The indices of bone resorption were strongly modified: the number (p <
      0.0001) and individual activity (p < 0.001) of the trabecular osteoclasts were
      prominently increased in the OVX rats. Ovariectomy resulted in a dramatic
      increase in the number of bone marrow MC (p < 0.0001), 97% of which were of the
      mucosal subtype. These results show that MC accumulate concomitantly with
      osteoclast generation in estrogen-deficient rats. Although the biological
      significance of this MC increase is unknown from these results, we hypothesize
      that MC might play a role in ovariectomy-induced bone loss similar to that they
      we previously proposed in a mechanically activated model of resorption.

PMID- 10940671
TI  - Comparison of amounts and properties of collagen and proteoglycans in condylar,
      costal and nasal cartilages.
AB  - In this study we compared the compositions of extracellular matrices of condylar,
      costal and nasal cartilages to characterize differences in growth patterns in
      relation to matrix composition. Condylar, costal and nasal cartilages of 25- and
      35-day-old rabbits were extracted and subjected to bio- and histochemical
      analysis to determine total amounts of collagen and amounts and aggregating
      properties of proteoglycans. We found that proteoglycan content and aggregate
      formation were greatest in nasal cartilage, and lower in costal and markedly
      lower in condylar cartilage. The amount of proteoglycans increased by varying
      amounts in all samples with age. Collagen content was highest in costal
      cartilage. In 25-day-old rabbits the quantity of collagen in condylar cartilage
      exceeded that in nasal cartilage. In 35-day-old rabbits the quantities were
      nearly the same. It is suggested that collagen does not only provide tensile
      strength, but counteracts forces responsible for interstitial growth such as
      osmotic pressure. Based on the results, it seems that the amount of proteoglycans
      is greater in cartilages, which have greater independent growth potential.
      Variations in increase in amount of proteoglycans with age could reflect
      differences in the timing of growth of such cartilages.

PMID- 10940672
TI  - Morphological study of cryopreserved human corneal endothelium.
AB  - The aim of the present paper is to describe the morphological changes that occur
      in human corneal endothelium as an immediate consequence of corneal
      cryopreservation. Therefore, 16 human donor corneas were cryopreserved with an
      original procedure at a 1 degrees C/min cooling rate in a freezing solution
      cryoprotected with 7% dimethylsulphoxide until a final temperature of -100
      degrees C was reached. After storage of the corneas in liquid nitrogen for
      periods ranging from 1 to 96 days (mean: 34.31 days), the corneas were thawed in
      a water bath at +37 degrees C. Eight additional control corneas were processed
      without cryopreservation. Morphological assessment of the endothelial layer was
      performed by scanning electron microscopy and trypan blue and alizarin red S
      vital staining. Results showed cryoinduced damage at variable degrees in all
      cryopreserved corneas. They were classified into three groups according to the
      intensity and extension of the cryoinduced damage: group I (n = 10): corneas with
      minor endothelial alterations consisting in the presence of microholes in the
      posterior cell membrane; group II (n = 1): corneas with generalized disruption of
      endothelial intercellular junctions and intact cell membranes; group III (n = 5):
      corneas with severe endothelial damage consisting of massive cell necrosis and
      complete alteration of the morphological pattern of the endothelium. All control
      corneas had intact endothelial layers. Cryoinduced damage cannot be completely
      avoided with the cryopreservation protocol tested. The high interindividual
      variability of the results observed is not related to the storage time of the
      cornea in liquid nitrogen.

PMID- 10940673
TI  - Neuromuscular remodeling and myofiber turnover in Rana pipiens' jaw muscles.
AB  - Larval jaw myofibers in Rana pipiens degenerate during metamorphosis and are
      replaced by a second wave of myogenesis that provides for adult jaw function.
      Trigeminal motoneurons that innervate larval myofibers transfer their preterminal
      axons to these adult successors where they establish new motor endplates.
      Silver/acetyl-cholinesterase histochemistry was used to compare innervation
      patterns in the larval and adult jaw adductor muscles and to plot the time course
      over which these changes occur. Innervation patterns differ substantially on the
      pre- and postmetamorphic myofiber populations. Jaw myofibers in the tadpole were
      unique by virtue of their exceedingly high level of distributed and focal
      polyinnervation. Each myofiber was innervated by approximately 10 small,
      junctional zones, most containing multiple axons, diffusely distributed over the
      length excepting small junctional free zones at either end of the muscle. In
      juvenile frogs, immediately following redeployment, the replacement myofibers had
      a polyinnervation pattern that mirrors that observed in the larvae. However, by
      12 weeks after metamorphosis there was a clear condensation of the end plates
      into multiple zones. Moreover, jaw myofibers in adult frogs had a reduced level
      of distributed and focal polyinnervation, less than 15% show signs of
      polyinnervation. The pattern of polyinnervation, axonal redeployment and myofiber
      degeneration is consistent with the hypothesis that the larval jaw muscles serve
      as a population of primary myofibers, ensuring survival of the trigeminal
      motoneurons through the prolonged period of larval development, while also
      providing a scaffold on which secondary jaw myofibers are constructed.

PMID- 10940674
TI  - Apolipoprotein E and intronic polymorphism of presenilin 1 and alpha-1
      antichymotrypsin in Alzheimer's disease and vascular dementia.
AB  - Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)
      antichymotrypsin (ACT) polymorphism and the association of the genotypes were
      examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia
      (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the
      ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35)
      and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in
      AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1
      intronic polymorphism was not associated with AD or VD and was not influenced by
      the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism
      of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1
      genotypes. The results confirm the association between ApoE epsilon 4 and AD and
      indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of
      ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association
      was shown between ACT allele A and PS-1 allele 1 in AD or VD.

PMID- 10940675
TI  - The expression of presenilin 1 mRNA in skin fibroblasts and brains from sporadic
      Alzheimer's disease.
AB  - We examined the expression of presenilin 1 (PS-1) mRNA in cultured skin
      fibroblasts taken from living patients with Alzheimer's disease (AD) and human
      brains taken postmortem from AD patients by RT-PCR analysis. The donors of
      fibroblasts consisted of 28 cases with AD and 19 neurological patient without
      dementia (CTL). The brains came from 17 cases with AD and 23 cases with CTL. We
      found that PS-1 mRNA levels in skin fibroblasts of AD patients were significantly
      higher than those of CTL patients (p < 0.0001). Moreover, we found that PS-1 mRNA
      levels in human brains with AD were significantly higher than in those with CTL
      (p < 0.0001). These findings suggest that high levels of PS-1 mRNA in AD may play
      an important role in developing AD and that the examination of PS-1 mRNA in skin
      fibroblasts may be helpful for the diagnosis of AD.

PMID- 10940676
TI  - Differential expression of metallothioneins in human prion diseases.
AB  - We herein report an immunohistochemical and a Western blot analysis on metal/free
      radical chelating proteins, metallothioneins (MTs; MT-I/II and MT-III), in the
      brains of human prion disease patients with or without prion protein gene
      mutation and polymorphism. Irrespective of the isoforms of MTs, the
      immunoreaction was detected in the cytoplasm and processes of the astrocytes in
      the cerebral cortex and white matter in normal controls and prion disease brains.
      Although the immunoreactivities for MTs in Creutzfeldt-Jakob disease (CJD) brains
      varied from case to case, they were generally dependent upon the disease
      duration. In CJD patients with a relatively long disease course, the
      immunoreaction for both MT-I/II and MT-III in the astrocytes was significantly
      reduced, and this finding was not modified by the genotypes of the patients. On
      the other hand, in patients with Gerstmann-Straussler-Scheinker syndrome, MT-I/II
      immunoreactivity in the astrocytes was exclusively reduced, while the
      immunoreaction for MT-III was relatively well preserved. Especially the
      astrocytes in the vicinities of the kuru plaques exhibited a weak or no
      immunoreaction even for MTs but a strong immunoreaction for glial fibrillary
      acidic protein. A quantitative Western blot analysis also revealed that MT-I/II
      protein accumulated in CJD brain with a short disease duration, whereas MT-III in
      CJD brain with a long disease duration was statistically significantly reduced in
      comparison to the normal brains. These findings suggest that the protein
      expression of MTs in the astrocytes is thus regulated differentially among human
      prion diseases and modified locally by such abnormal prion protein depositions as
      kuru plaques.

PMID- 10940677
TI  - White matter lesions in dementia: an MRI study on blood-brain barrier
      dysfunction.
AB  - White matter lesions (WMLs) and blood-brain barrier (BBB) dysfunction are common
      in dementia. Both conditions may be a consequence of small-vessel disease, in
      which case the BBB damage would be suspected to be located to the WMLs. To
      further evaluate the nature of WMLs in dementia we examined 10 demented patients
      with WMLs, including 5 cases with elevated CSF/serum albumin ratios as an
      indication of BBB damage. An optimised gadolinium (Gd)-enhanced MRI technique was
      used including a double dose of Gd, a 30-min scan time after injection and
      analysis of the MR signal in the WMLs as a function over time. Results showed no
      significant changes in MR signal in the WMLs after contrast administration. We
      conclude that WMLs are not connected to BBB damage to such a degree that is
      detectable with this method and that the elevated CSF albumin might have another
      origin.

PMID- 10940678
TI  - Comprehension of emotions: comparison between Alzheimer type and vascular type
      dementias.
AB  - This study investigated the ability of recognizing emotion in dementia. Twenty
      five patients with dementia of the Alzheimer type (DAT), 25 patients with
      vascular dementia (VD), and 12 normal control subjects were evaluated as to
      general cognition, visuoperception and emotion recognition. The score on the
      emotion recognition task significantly correlated with that of the Mini-Mental
      State Examination for VD patients while this was not the case for DAT patients.
      Moreover, VD patients performed significantly worse than DAT patients on the
      emotion recognition task in spite of the fact that there was no difference in the
      general cognitive and visuoperceptual abilities between them. The result of this
      study coupled with the past studies led to the hypothesis that the relationship
      between intellectual deficits and the deterioration in recognizing emotions
      differs according to type of dementia. Caregivers in nursing homes and hospitals
      need to take into account their patients' intellectual deficits but also their
      deteriorating ability of identifying emotions.

PMID- 10940679
TI  - Frontotemporal dementia can be distinguished from Alzheimer's disease and
      subcortical white matter dementia by an anterior-to-posterior rCBF-SPET ratio.
AB  - Sixteen patients with frontotemporal dementia (FTD), 27 with early-onset
      Alzheimer's disease, 25 with late-onset Alzheimer's disease, 19 with subcortical
      white matter dementia (SWD) and 28 normal controls underwent semiquantitative
      regional cerebral blood flow measurement (rCBF) using single-photon emission
      tomography (SPET; (99m)Tc-HMPAO) and either computerized tomography (CT) or
      magnetic resonance imaging (MRI) of the brain. An anterior-to-posterior rCBF-SPET
      ratio (mesial superior frontal gyrus/medial temporal lobes) was calculated, which
      significantly separated the FTD group from the other dementia groups and controls
      with a sensitivity of 87.5% and a specificity of at least 78.6%. CT/MRI was found
      to be helpful in the differential diagnosis between FTD and SWD. In FTD patients,
      the mesial superior frontal gyrus, near the polus frontalis, was found to be the
      region with the most reduced rCBF values.

PMID- 10940681
TI  - Behavioral differences between white matter lacunar dementia and Alzheimer's
      disease: a comparison on the neuropsychiatric inventory.
AB  - BACKGROUND AND PURPOSE: Behavioral abnormalities account for much of the
      morbidity of vascular dementia (VaD) and Alzheimer's disease (AD). The goals of
      the study were to compare the behavioral changes in patients with VaD associated
      with ischemic white matter subcortical changes and lacunar infarctions (VaD-WSI)
      to those in patients with AD. METHODS: Thirty outpatients with VaD and multiple
      lacunar infarctions in the periventricular white matter and 30 AD patients,
      matched for age and severity of dementia, were enrolled in this prospective
      study. The behavioral abnormalities of these patients were assessed by
      interviewing their caregivers with the Neuropsychiatric Inventory. RESULTS: A
      similar spectrum of noncognitive behavioral changes was found in AD and WSI
      patients. In VaD-WSI, the severity of delusions, hallucinations, aggression,
      irritability, aberrant motor behavior, nighttime behavior and appetite changes
      was correlated with cognitive decline, whereas depression, apathy, anxiety and
      euphoria were unrelated to the severity of dementia. In AD, none of the
      behavioral changes correlated with the severity of dementia. CONCLUSION:
      Behavioral changes are frequent in VaD-WSI and are present regardless of the
      severity of the cognitive decline. It is therefore important to assess behavioral
      as well as cognitive changes at early stages of the illness, to ensure
      appropriate treatment.

PMID- 10940680
TI  - First symptoms--frontotemporal dementia versus Alzheimer's disease.
AB  - Frontotemporal dementia (FTD) is often misdiagnosed as Alzheimer's disease (AD).
      We hypothesized that the first symptoms associated with FTD would be different
      from those seen in AD and that the first symptoms in FTD would reflect loss of
      function in the frontal region with the greatest degree of degeneration. The
      objective of the study was to compare the earliest symptoms in patients with FTD
      and AD, and to delineate the symptoms that were associated with right, left or
      bilateral frontotemporal degeneration in FTD. The first symptoms in 52 FTD and
      101 AD patients were determined in retrospect. Based on functional imaging
      studies, the FTD patients were divided into those with predominantly bilateral (n
      = 15), left-sided (n = 19) and right-sided (n = 18) patterns of atrophy. The
      results showed that disinhibition, social awkwardness, passivity and loss of
      executive function were more common in FTD, while memory loss was more common in
      AD. Disinhibition was greatest in the asymmetric right-sided group, language
      dysfunction was commonest in the asymmetric left-sided group and loss of
      executive function was most frequent in the bilateral group. In summary,
      different first symptoms appeared in FTD and AD, which may help distinguish
      between the diseases. The anatomic site for FTD largely determined the kind of
      first symptoms.

PMID- 10940682
TI  - Molecular genetics of neuroendocrine tumors.
AB  - Through insights into the molecular genetics of neuroendocrine tumors (NETs), the
      genes predisposing to multiple endocrine neoplasia (MEN) syndromes were
      identified. In MEN1, tumors occur in the parathyroids, endocrine pancreas,
      anterior pituitary, adrenal glands and thymic neuroendocrine tissues. The MEN1
      gene encodes a putative growth-suppressor protein, menin, binding JunD, a
      transcriptional factor belonging to the AP-1 complex. However, new partners
      binding menin remain to be found. The MEN1 gene might be involved in 1-50% of
      sporadic NETs. Another critical mechanism involved in NETs is the deregulation of
      the RET-signalling pathways by oncogenic point mutations responsible for MEN2
      syndromes. MEN2 refers to the inherited forms of medullary thyroid carcinoma. The
      RET proto-oncogene, a tyrosine-kinase receptor, is activated by missense
      mutations occurring either in the extracellular dimerization domain or
      intracellular tyrosine kinase catalytic regions. In both cases the receptor is
      constitutionally activated in the absence of natural ligands. Endocrine tumors
      also belong to the clinical pattern of Recklinghausen (NF1) and von Hippel-Lindau
      (VHL) diseases. The genes for both syndromes have been characterized and provide
      new pathways for endocrine tumorigenesis related to G-protein physiology (NF1)
      and transcriptional regulation and/or endothelial cell proliferation (VHL),
      respectively. Here, we propose a basic overview of recent data on genetic events
      leading a normal endocrine cell towards a fully malignant phenotype.

PMID- 10940683
TI  - Biological and molecular aspects of gastroenteropancreatic neuroendocrine tumors.
AB  - Neuroendocrine tumors of the digestive tract are rare entities characterized by
      significant phenotype differences and traditionally considered to originate from
      cells of the diffuse endocrine system of the pancreas and gut. Two major
      categories with significant phenotype and clinical behavior differences are
      identified as well-differentiated and poorly differentiated tumors. Investigation
      on the molecular basis of tumor development points to an important role for the
      multiple endocrine neoplasia syndrome type-1 (MEN1) gene because of its frequent
      abnormality observed both in well-differentiated and poorly differentiated
      tumors. Other genes are possibly involved, though the available data need support
      from studies on larger series of tumors.

PMID- 10940684
TI  - Somatostatin receptors.
AB  - Somatostatin is a neuropeptide produced by neuroendocrine, inflammatory and
      immune cells in response to different stimuli. Somatostatin inhibits various
      cellular functions including secretions, motility and proliferation. Its action
      is mediated by five specific somatostatin receptors (sst1-sst5) which belong to
      the G protein-coupled receptor family. The five receptors bind the natural
      peptide with high affinity but only sst2, sst5 and sst3 bind the short synthetic
      analogues used to treat patients with neuroendocrine tumors. The five receptors
      are expressed in various normal and tumor cells, the expression of each receptor
      being receptor subtype and cell-type specific. In neuroendocrine tumors, sst2 is
      highly expressed whereas in advanced pancreatic adenocarcinoma as well as high
      grade colorectal carcinomas, its expression is lost. Each receptor subtype is
      coupled to different signal transduction pathways through G protein-dependent and
      -independent mechanisms. The synthesis of selective agonists for each receptor
      and the recent development of genetic animal models with selective deletion of
      receptor subtype provide tools for establishing some of the biological roles of
      the receptors. sst1, 2 and 5 mediate inhibition of GH secretion whereas sst2 and
      sst5 mediate inhibition of glucagon secretion and insulin secretion,
      respectively.

PMID- 10940685
TI  - Tumor markers in neuroendocrine tumors.
AB  - Most neuroendocrine tumors produce and secrete a multitude of peptide hormones
      and amines. Some of these substances cause a specific clinical syndrome:
      carcinoid, Zollinger-Ellison, hyperglycemic, glucagonoma and WDHA syndrome.
      Specific markers for these syndromes are basal and/or stimulated levels of
      urinary 5-HIAA, serum or plasma gastrin, insulin, glucagon and vasoactive
      intestinal polypeptide, respectively. Some carcinoid tumors and about one third
      of endocrine pancreatic tumors do not present any clinical symptoms and are
      called 'nonfunctioning' tumors. Therefore, general tumor markers such as
      chromogranin A, pancreatic polypeptide, serum neuron-specific enolase and
      subunits of glycoprotein hormones have been used for screening purposes in
      patients without distinct clinical hormone-related symptoms. Among these general
      tumor markers chromogranin A, although its precise function is not yet
      established, has been shown to be a very sensitive and specific serum marker for
      various types of neuroendocrine tumors. This is because it may also be elevated
      in many cases of less well-differentiated tumors of neuroendocrine origin that do
      not secrete known hormones. At the moment, chromogranin A is considered the best
      general neuroendocrine serum or plasma marker available both for diagnosis and
      therapeutic evaluation and is increased in 50-100% of patients with various
      neuroendocrine tumors. Chromogranin A serum or plasma levels reflect tumor load,
      and it may be an independent marker of prognosis in patients with midgut
      carcinoids.

PMID- 10940686
TI  - Imaging procedures in neuroendocrine tumours.
AB  - PURPOSE: To give recommendations for diagnostic imaging workflow in suspected
      neuroendocrine tumours. MATERIALS AND METHODS: Recommendations for imaging
      workflow were elaborated by consensus of researchers in neuroendocrine tumours.
      RESULTS: Workflow charts are presented for: (1) nonfunctional and functional
      endocrine tumours of the pancreas (except insulinoma); (2) insulinoma; (3) ECL
      cell tumour; (4) assessment of unknown primaries in functional and nonfunctional
      neuroendocrine tumours of the gut; (5) assessment of metastases in functional and
      nonfunctional neuroendocrine tumours of the gut. CONCLUSIONS: The workflow charts
      facilitate diagnosis of neuroendocrine tumours as well as the design of
      controlled studies.

PMID- 10940687
TI  - Endoscopic ultrasonography of neuroendocrine tumours.
AB  - Neuroendocrine tumours (NETs) of the upper gastrointestinal tract are mainly
      located in the pancreas, stomach or duodenum. The aims of preoperative work-up
      are the localization of primary tumour(s), determination of local tumour
      invasion, of lymph node metastases and of the hormones secreted by the tumour.
      Endoscopic ultrasonography (EUS) offers ideal conditions to localize and stage
      NETs of the foregut. We report our results in localizing and staging NETs of the
      foregut in 40 patients examined between 1990 and 1997 by EUS, somatostatin
      receptor scintigraphy (SRS), computed tomography (CT), magnetic resonance imaging
      (MRI) and transabdominal ultrasound (US). EUS shows the highest sensitivity in
      localizing insulinomas compared with SRS, US, CT and MRI. US and EUS should be
      the first-line diagnostics if insulinoma has been proven by a fasting test.
      Further diagnostic procedures are unnecessary in most cases. Further diagnostics
      such as CT or MRI to search for distant metastases are necessary in large tumours
      or local invasive tumours. EUS shows the highest accuracy to detect or exclude
      pancreatic gastrinomas, but fails to detect extrapancreatic gastrinomas in about
      50%. The combination of EUS and SRS gives additional information. First-line
      diagnostics in gastrinoma patients should be SRS and CT or MRI. If no metastases
      are detected, EUS should be the next preoperative imaging procedure. In
      nonfunctional NETs, EUS provides the best information on local tumor invasion and
      regional lymph node involvement.

PMID- 10940688
TI  - Natural history of neuroendocrine enteropancreatic tumors.
AB  - Neuroendocrine enteropancreatic tumors (NEEPTs) include tumors developing from
      the pancreatic islets and the duodenal loop, and those developing from gut
      serotonin-secreting cells (mid-gut carcinoids). When functioning, they are rare
      tumors with frequently inconsistant clinical and biological characteristics.
      Provocative dynamic tests are very useful. Their natural history, with the
      exception of insulinomas and mid-gut carcinoids, is still incompletely known due
      to their rarity, relatively recent description, slow evolution and the absence of
      definitive reliable markers for prognosis. The following factors affect the
      natural history of NEEPTs. (1) Inclusion or not within the spectrum of multiple
      endocrine neoplasia type-1 (MEN1), such an integration often dramatically
      modifies the management strategy. In patients with MEN1, NEEPTs are often
      multiple, diffusely spread in the duodenopancreatic area and of small size.
      Definite cure by surgery is then very scarce. Mid-gut carcinoid tumors are the
      most protean NEEPTs. In contrast to appendiceal carcinoids, usually with a benign
      course, mid-gut carcinoids have a more malignant course and are very common
      indeed: local transmural invasion, early metastasis to lymph nodes and/or liver,
      and symptoms from hormone oversecretion. Carcinoid syndrome is usually well
      controlled by long-acting somatostatin analogs. (2) Disease spreading, i.e. liver
      and bone metastases, are the major causes of death in patients with NEEPTs. Liver
      metastases (LMs) are synchronous in about 75% of the patients with LMs but may
      develop during follow-up (about 25% of the patients with LMs were without LMs at
      the initial evaluation). Development of bone metastases has a very poor prognosis
      accompanying LM progression.

PMID- 10940689
TI  - Interventional treatment of gastrointestinal neuroendocrine tumours.
AB  - Neuroendocrine (NE) tumours of the gastrointestinal tract (carcinoids and
      endocrine pancreatic tumours) are rare diseases. In the presence of liver
      metastases these patients may suffer from disabling symptoms due to hormone
      overproduction. Patients with localized disease can be resected for cure and also
      patients with liver metastases can undergo potentially curative tumour resection.
      However, long-term follow-up of the latter cases indicates frequent recurrence of
      tumour. Using close biochemical monitoring of tumour markers combined with newer
      techniques for tumour visualization, these recurrences can often be diagnosed at
      an early stage so that repeat surgical procedures can be performed. During the
      last years very active surgery has been recommended for NE tumours, many of which
      have a relatively slow growth. Even in patients not amenable to curative liver
      surgery, debulking can be considered if the main tumour burden can be safely
      excised. The primary aim of this type of treatment is palliation of hormonal
      symptoms. An important question is whether the aggressive treatment actually
      prolongs survival. No prospective studies have been performed. Such studies are
      hampered by the lack of strict surgical programs running over long periods and
      the relative rarity of NE tumours. Liver transplantation may be another treatment
      modality in selected cases.

PMID- 10940691
TI  - Chemotherapy in the treatment of neuroendocrine malignant tumors.
AB  - The efficacy of chemotherapy in digestive neuroendocrine tumors (NET) depends on
      primary site and histological differentiation. Many reports have suggested a
      superior activity of chemotherapy for pancreatic NET than for metastatic
      carcinoid tumors with response rates ranging from 40 to 60% compared to 20%. The
      standard chemotherapy for pancreatic NET is a combination of adriamycin and
      streptozocin and to a lesser extent a combination of 5FU and streptozocin. In
      contrast, there is no clear standard chemotherapy for carcinoid tumors and if
      most oncologists use a combination of 5FU and streptozocin in the case of
      advanced, progressive and nonresectable carcinoid tumors, the results are mostly
      poor and the benefit seldom counterbalances its toxicity. In these carcinoid
      tumors the combination of hepatic artery ischemia alternating with chemotherapy
      has given impressive results in one study, which, however, have never been
      confirmed. Tumor cell differentiation is a major prognostic factor and some
      reports have suggested a higher chemosensitivity for undifferentiated or poorly
      differentiated NET with tumor response rates ranging from 41 to 69% when a VP16
      CDDP combination is used. This chemosensitivity is, unfortunately, as in small
      cell lung carcinomas, of short duration. Related to this special problem and the
      number of other active treatments in NET, the place of chemotherapy always has to
      be discussed in a multidisciplinary fashion. Surgical excision,
      chemoembolization, interferons and somatostatin analogues have to be emphasized
      and eventually combined with chemotherapy, especially in slowly growing tumors.
      New active chemotherapy regimens have to be tested clearly in this orphan group
      of tumors which does not hold much interest to the pharmaceutical companies.

PMID- 10940690
TI  - OctreoTher: ongoing early clinical development of a somatostatin-receptor
      targeted radionuclide antineoplastic therapy.
AB  - OctreoTher ((90)Y-DOTA-D-Phe(1)-Tyr(3)-octreotide, a.k.a. (90)Y-SMT 487) consists
      of a somatostatin peptide analogue (Tyr(3)-octreotide), coupled with a complexing
      moiety (DOTA), and labeled with a tightly bound beta-emitter (yttrium-90). By
      targeting somatostatin receptor-positive tumors (as imaged by OctreaScan it may
      deliver a tumoricidal dose of radiation. Phase I clinical trials, conducted in
      patients with neuroendocrine tumors, established the safety and tolerability of
      the dose selected for further study and demonstrated the capacity of OctreoTher
      to deliver radiation doses to tumors that resulted in significant neuroendocrine
      tumor shrinkage. Novartis-sponsored phase II studies will soon begin to test the
      efficacy of OctreoTher in breast and small cell lung cancer. A fixed-dose regimen
      of 120 mCi/cycle x 3 cycles administered with concomitant amino acid infusion has
      been chosen for the study. Phase I data and published literature support that
      this fixed dose regimen will be safely tolerated.

PMID- 10940692
TI  - Hepatic arterial chemoembolization in the management of advanced digestive
      endocrine tumors.
AB  - The management of advanced digestive endocrine tumors is often challenging. Liver
      metastases are usually diffuse at the time of diagnosis, and surgical resection
      is rarely feasible. Objective response rates with systemic chemotherapy are
      disappointing. Arterial hypervascularization of most liver metastases from
      digestive endocrine tumors argues in favor of hepatic arterial chemoembolization
      (HACE). It is assumed that embolization-induced ischemia sensitizes tumor cells
      to cytotoxic drugs, whose tumor concentrations are increased by blood flow
      slowing down. The aims of HACE are: (1) to control otherwise untractable hormone
      related symptoms, particularly the carcinoid syndrome (>50% urinary 5-HIAA
      decrease: 57-91%) and insulinoma-related life-threatening hypoglycemias; (2) to
      inhibit tumor growth (objective response rates: 33-80%; mean duration: 6-42.5
      months), and (3) to improve patients' survival. The postembolization syndrome,
      usually mild and transient, is the commonest side effect. Major extrahepatic
      complications are rare. In conclusion, HACE seems to be an attractive alternative
      treatment for diffuse (unresectable) and progressive metastases confined to the
      liver in patients with digestive endocrine tumors, mainly following unsuccessful
      systemic chemotherapy. Further studies assessing the long-term results of HACE
      and comparing it to other treatments, particularly systemic chemotherapy, are
      needed.

PMID- 10940693
TI  - Treatment of neuroendocrine GEP tumours with somatostatin analogues: a review.
AB  - BACKGROUND: Somatostatin and its long-acting analogues are effective in symptom
      control in patients with functionally active neuroendocrine GEP tumours. Several
      in vitro and in vivo reports suggest that they are also able to control tumour
      growth. METHODS: Critical review of published data on the effect of long-acting
      somatostatin analogues on symptom and growth control in patients with metastatic
      neuroendocrine GEP tumours. RESULTS: With the exception of insulinoma and
      gastrinoma, octreotide acetate and other long-acting somatostatin formulations
      are currently the therapeutic principle of first choice to control hormone
      mediated symptoms. The consequences of gastric acid hypersecretion in patients
      with Zollinger-Ellison syndrome are best controlled by proton pump inhibitors.
      Available data on growth control indicate that stabilization of tumour growth
      seems to be the most beneficial antiproliferative effect occurring in up to 50%
      of patients. This effect is limited. However, it is unknown which tumour entity
      responds best to long- acting somatostatin analogues. CONCLUSION: Additional
      studies in patients with known spontaneous tumour growth and avoiding a mix-up of
      different entities of neuroendocrine malignancies are necessary to identify
      subpopulations of neuroendocrine tumours which respond to long-acting
      somatostatin analogues in terms of longer lasting growth inhibition.

PMID- 10940694
TI  - Interferon in the management of neuroendocrine GEP-tumors: a review.
AB  - Interferon has been known to be an effective antiviral and antitumor agent since
      the 1960s. However, a large majority of solid tumors did not respond to this kind
      of treatment. In early 1980s, alpha interferon was introduced in the management
      of classical midgut carcinoids with promising results. Since then, more than 500
      patients have been treated with alpha interferon worldwide and published in the
      literature. The median dose has been 5 million units 3-5 times per week
      subcutaneously. The subjective response rate is about 60%, biochemical responses
      in 44% and tumor responses in 11% of the patients. There are very few randomized
      control trials at the moment which make survival analysis difficult but in
      different centers median survivals from start of treatment in malignant midgut
      carcinoids has been reported to be more than 3 years. The mechanisms of action of
      alpha interferon are direct effects on the tumor cells by inhibiting the cell
      proliferation via cell cycle block G1-S phase. Induction of interferon inducable
      genes, such as p-21, p-27, 2-5-A-synthetase, PKR, IRF-1, IRF-2. All these
      contribute to reduction of the growth potential of the tumor. Furthermore, alpha
      interferon exerts an immunomodulatory effect stimulating natural killer cells,
      macrophages and also presents anti-angiogenetic effects. In the future, long
      acting formulations of recombinant alpha interferons will come into clinical use,
      such as polyethylene glycosylated interferons. It will facilitate the treatment
      for the patients and also perhaps reduce the side effects, which are sometimes
      significant during treatment with alpha interferon. It might also be possible to
      give higher doses of alpha interferon with hopefully improved clinical efficacy.

PMID- 10940695
TI  - Advanced prostate cancer is associated with a decrease in serum luteinizing
      hormone.
AB  - OBJECTIVE: Depletion of serum LH by LHRH agonists is used as a therapeutic
      treatment in hormone-sensitive prostate cancer (PCa). However, little information
      on serum LH in different patient groups is available. METHODS: Patients with
      biopsy-proven PCa, men with BPH (biopsy-proven absence of PCa), two subgroups
      (serum PSA <4 ng/ml; PCa and BPH), and a PCa cohort before and after radical
      prostatectomy were analyzed for serum LH, testosterone (T), dihydrotestosterone
      (DHT), total and free PSA by immunological procedures. RESULTS: PCa patients with
      cancer volumes >10 cm(3), or with advanced Gleason scores, had significantly
      lower LH values than men in a cancer-free control group (PSA <4 ng/ml). Eight
      weeks after radical prostatectomy, LH levels had returned to the level of the
      control group (p<0.0001). These alterations were not accompanied by corresponding
      changes of serum androgens. Introduction of a PSA/LH ratio appeared to increase
      the differences between BPH and PCA groups ranked according to Gleason scores,
      versus PSA or LH alone. However, the calculation of ROC curves indicated that
      PSA/LH ratios may not improve the discrimination of malignant and benign forms of
      the disease, compared to presently used parameters. CONCLUSIONS: A significant
      reduction of circulating LH is observed in the most advanced forms of PCa. The
      effect does not come about by T- or DHT-mediated feedback inhibition. Since LH
      values after prostatectomy returned to practically the same levels as seen in the
      control group (BPH with <4 ng/ml PSA), it appears that the healthy prostate has
      no marked influence on serum LH while advanced PCa induces a decrease in serum
      LH.

PMID- 10940696
TI  - Low PSA metastatic androgen- independent prostate cancer.
AB  - OBJECTIVES: To describe the clinical parameters of low PSA, progressive
      metastatic androgen-independent prostate cancer. METHODS: From April 1995 to May
      1999, we selected 18 patients with clinically progressive androgen-independent
      prostate cancer and low PSA (</=10 ng/ml). Patients received cisplatin-based
      therapy. Specimens from the primary tumor were reviewed and neuroendocrine
      differentiation was determined with chromogranin-A and neuron-specific enolase
      immunocytochemical staining. RESULTS: The median initial PSA level was 1.6 ng/ml
      (0-9.5). Each patient demonstrated elevation of at least one of the following
      markers: carcinoembryonic antigen, CA 19-9, CA15-3 and CA 125 CA. Metastases
      involved bone in 11 patients (61.1%) - 5 (27.7%) blastic, 2 (11.1%) lytic, and 4
      (22.2%) combined - liver in 10 patients (55.5%), lymph nodes in 8 (44.4%), and
      lung in 6 (33.3%); solitary sites as orbit, skin and spleen were noted as well. A
      prostatic pelvic mass was detected in 13 patients (72.2%). Of the 12 patients who
      consented to chemotherapy, 8 (66.6%) achieved an objective response (95% CI, 34.
      8-90%), including 1 patient with complete response. Hematoxylin and eosin
      evaluation revealed two major groups: neuroendocrine tumors, either pure small
      cell cancer in 6 patients (37.5%) or combined small cell cancer and
      adenocarcinoma in 8 (50%), and predominant poorly differentiated prostate cancer
      in 2 (12.5%). Neuroendocrine immunoreactivity was detected in all the specimens.
      CONCLUSIONS: Progressive androgen-independent prostate cancer with low serum PSA
      is characterized by visceral metastases, high proportion of lytic bone disease,
      sensitivity to cisplatin-based chemotherapy, and histological features of small
      cell or poorly differentiated prostate cancer. In this subgroup of patients,
      selection of the therapeutic approach can be based on clinical parameters. The
      rise of the serum markers may aid in the diagnosis and follow-up of these
      patients.

PMID- 10940697
TI  - Combination chemotherapy following adrenal suppression in androgen- independent
      prostate cancer.
AB  - OBJECTIVES: Recent trials with modern chemotherapy have demonstrated activity in
      androgen-independent prostate cancer, but all focused on patients with
      progression following androgen suppression or antiandrogen withdrawal. Limited
      data are available on the activity of chemotherapy in androgen-independent,
      hormone-refractory (progressing following adrenal suppression) prostate cancer.
      We evaluated the activity of estramustine combined with vinblastine in this
      subset of androgen-independent prostate cancer. METHODS: From January 1995 until
      April 1999, 19 patients with hormone-refractory prostate cancer received
      estramustine 140 mg p.o., three times daily along with weekly vinblastine 5
      mg/m(2). RESULTS: A decrease in prostate-specific antigen of 50% or more was
      noted in 12 patients (63.1%, 95% CI 38.3-83.7%). The median decrease in prostate
      specific antigen was 71.2% (range 50.5-85.2%). None of the 7 patients with
      measurable soft-tissue disease showed an objective response. The median survival
      from onset of chemotherapy was 6 (range 1.4-27.7) months and from initiation of
      adrenal suppression 16.9 (range 3.8-40. 5) months. CONCLUSIONS: The combination
      of estramustine and vinblastine is capable of inducing activity in androgen
      independent prostate cancer progressing after adrenal suppression. In our small
      sample, the survival rate was low, and we obtained no response in soft-tissue
      sites. Future prospective trials are needed to determine the benefit of
      sequential versus simultaneous incorporation of adrenal suppression with
      chemotherapy in the management of androgen-independent prostate cancer.

PMID- 10940698
TI  - Quality of life assessment in patients with hormone-resistant prostate cancer
      treated with epirubicin or with epirubicin plus medroxy progesterone acetate - is
      it feasible?
AB  - OBJECTIVES: The optimal palliative treatment in patients with advanced hormone
      resistant prostate cancer (AHRPC) is still under investigation. We studied the
      effect of epirubicin, alone or combined with medroxy progesterone acetate (MPA),
      in this particular patient group. The aim of the study was to investigate the
      feasibility of quality of life (QOL) measurement and to ascertain whether MPA
      added to epirubicin produces a better QOL than epirubicin alone. METHODS: Of 28
      randomized patients with symptomatic AHRPC, 26 were eligible for the study.
      Fourteen of them received epirubicin (100 mg/m(2) i.v.) every 3 weeks in
      combination with an oral dose of 500 mg of MPA twice daily. Twelve patients
      received epirubicin alone. For the QOL assessment, the Rotterdam Symptom
      Checkliste was used. Toxic side effects of chemotherapy were assed by the WHO
      criteria. Subjective responses included performance status and pain score.
      RESULTS: Compliance in completing QOL questionnaires was high (87.5%). In none of
      the QOL domains studied did any of the patients, irrespective of their treatment,
      experience an improvement in their QOL. Moreover, after 12 and 24 weeks, patients
      in both treatment arms experienced a significant worsening of physical symptom
      distress when compared to study entry. Toxicity was moderate to severe. A
      biochemical response (drop in prostate-specific antigen of more than 50%) was
      observed in 5 out of 26 patients (19.1%) and a subjective response in 7 out of 26
      patients (26.9%). The median survival for all patients was 30 weeks. There was no
      statistically significant difference between the two arms. Performance status and
      the global QOL as judged by the patients themselves were associated with the
      duration of survival. No relation was found between the initial observed
      subjective response and survival. CONCLUSIONS: The feasibility of measuring QOL
      in patients with symptomatic AHRPC is demonstrated in the present study.
      Subjective and biochemical responses were observed in both treatment arms, but
      these were not translatable as improved measured QOL domains.

PMID- 10940699
TI  - Randomised prospective trial of contact laser prostatectomy (CLAP) versus visual
      laser coagulation of the prostate (VLAP) for the treatment of benign prostatic
      hyperplasia. 2-year follow-up.
AB  - OBJECTIVE: To determine the long-term efficacy and complications of visual laser
      coagulation/ ablation, VLAP (side-firing fibre) and direct contact laser
      ablation, CLAP (sapphire-tipped fibre) of the prostate in the treatment of benign
      prostatic hyperplasia (BPH). PATIENTS AND METHODS: Patients with clinical BPH,
      obstructed at voiding cystometry, were recruited and randomised to undergo either
      CLAP (21 patients) or VLAP (17 patients). At baseline, 1, 6, 12 and 24 months,
      patients underwent clinical evaluation, International Prostate Symptom Score
      (IPSS), uroflowmetry, post-void residual urine volume, and pressure/flow
      urodynamics. RESULTS: The mean operating time for CLAP was 37.7 min and 24.5 min
      for VLAP. There was minimal morbidity with only 5 men requiring bladder
      irrigation after CLAP, 1 of whom had a blood transfusion. No patient required
      irrigation after VLAP. The mean catheterisation time after CLAP was 4.5 days
      (range 1-31 days) and 13.2 days (range 7-70 days) after VLAP. IPSS and Qmax
      improved significantly and maintained at 2 years. After CLAP, the IPSS decreased
      from 20.9 to 13.5 at 2 years while Qmax rose from 10 to 15.5 ml/s at 2 years.
      After VLAP, the IPSS decreased from 21.8 to 13.3 at 2 years while Qmax rose from
      10 to 15. 9 ml/s. There was no difference between CLAP and VLAP. Pressure/flow
      urodynamics at 6 months showed reduced bladder outflow obstruction. CONCLUSIONS:
      CLAP and VLAP offer the same improvement in flow rates and symptoms at 2years.
      Both procedures lead to minimal morbidity, but the excellent haemostasis that is
      achieved at VLAP makes it of more use in treating patients at high risk of
      haemorrhage after surgery.

PMID- 10940700
TI  - A new prostatic stent for the treatment of benign prostatic hyperplasia in high
      risk patients.
AB  - OBJECTIVES: The objective of this study was to evaluate the efficacy and safety
      of a new prostatic stent (Trestle((R)), Boston Scientific Microvasive) for the
      treatment of BPH in patients with complete urinary retention and considered to be
      inoperable. METHODS: The efficacy of the stent was evaluated in terms of return
      of micturition, level of patient satisfaction, uroflowmetry and residual urine.
      Any stents removed were examined by infrared spectrophotometry for the presence
      of crystalline encrustations. RESULTS: From December 1997 to April 1999, 20
      stents were inserted under local anaesthesia in 17 patients aged 54-90 years.
      Stents remained in place for an average of 3.5 months. Two migrations were
      reported. The mean maximum flow rate was 13.7 ml/s and the mean residual urine
      was 110 ml. The infrared spectrophotometry study revealed a glycoprotein film on
      stents in place for 1-6 months, accompanied by uric acid crystals on stents in
      place for 9 months. CONCLUSION: The Trestle prostatic stent is effective and
      constitutes a good alternative to surgical treatment in patients with a high
      operative risk.

PMID- 10940701
TI  - Long-term risk of salvage cystectomy after radiotherapy for muscle-invasive
      bladder cancer.
AB  - OBJECTIVES: To establish the long-term outcome for muscle-invasive transitional
      cell carcinoma of the bladder treated by radiotherapy with or without neoadjuvant
      cisplatin. METHODS: 159 patients with T2-T4a NX M0 bladder cancer were entered
      into a prospective randomized trial between June 1984 and June 1988. Follow-up
      was by 3-monthly cystoscopy in the first year, 6-monthly the next 2 years and
      yearly thereafter. Salvage surgery was performed at the discretion of the
      participating clinician. RESULTS: Minimum follow-up was 9 (median 11) years, at
      which time 29 patients (18%) remain alive. Median survival was 24 months with no
      difference between the treatment groups (chi(2) = 0.08, p = 0.77). Overall
      cystectomy rate was 24% (radiotherapy alone 20%, combined therapy 28%; p = 0.24).
      Median time to cystectomy from primary treatment was 12 months; range 56 days to
      10 years. The risk of cystectomy was 11, 10 and 7% for the first, second and
      third years after radiotherapy respectively, and 8% in total after the third
      year. The proportion of patients alive in each successive year who had required a
      cystectomy was between 20 and 30% for 5 of the first 8 years after treatment.
      CONCLUSIONS: Salvage cystectomy is necessary in a quarter of patients after
      radiotherapy and this can be needed up to 10 years after treatment. During this
      time, multiple invasive procedures are likely to be performed, resulting in
      significant patient morbidity and cost. Patients should be fully counselled about
      the need for prolonged surveillance and the persisting risk of salvage surgery
      when deciding between primary cystectomy and radiotherapy.

PMID- 10940702
TI  - Evaluation of P53 protein overexpression, Ki67 proliferative activity and mitotic
      index as markers of tumour recurrence in superficial transitional cell carcinoma
      of the bladder.
AB  - OBJECTIVES: To confirm the interrelationship between p53, ki67, mitotic index
      with others known prognostic factors such us stage, grade, multifocality, tumour
      size, history of recurrence in transitional cell carcinoma (TCC) of the bladder
      and to determine the prognostic impact of p53, Ki67 and mitotic index in
      predicting recurrence in superficial bladder cancer. METHODS: Two hundred and
      fourteen patients with apparently superficial TCC of the bladder underwent TURBT
      and the 192 histologically Ta-T1 were divided into 104 primary lesions (group 1,
      mean follow-up 26 months) and 88 recurrent tumours (group 2, mean follow-up 28
      months). Data concerning focality, tumour size, number of recurrences and
      recurrence-free survival were considered in each patients. All samples were
      immunohistochemically stained with p53 and Ki67 monoclonal antibodies. Mitotic
      index (MI) was calculated on haematoxylin and eosin stained sections. RESULTS:
      Recurrence-free survival was significantly lower in superficial recurrent tumours
      (group 2) compared with primary tumours (group 1). P53 staining was correlated
      with grade and stage for both 5 and 20% positivity thresholds. Ki67 and MI were
      significantly different over strata defined by stage, grade and focality in both
      patients groups but only Ki67 showed a correlation with p53 status. Recurrence
      free survival could not be predicted either by p53 status or MI. A 20% cut-off
      level of Ki67 staining resulted a good predictor of recurrence in group 1 Ta
      T1/G1-G2 tumours (p = 0.03). Only Ki67 and multifocality were found to be
      independent prognostic factors of recurrence in multivariate analysis.
      Stratifying Ta-T1/G1-G2 patients according to these variables, Ki67 provided a
      useful tool to predict early recurrence in monofocal lesions from both groups.
      CONCLUSIONS: P53 and MI despite a fairly good correlation with traditional
      prognostic factors in bladder TCC seem to play no role in the prediction of
      tumoural recurrence. A Ki67 index over 20% predicts those single well
      differentiated (Ta-T1/G1-G2) tumours which are likely to recur within one year of
      treatment.

PMID- 10940703
TI  - Comparison of metabolic risk factors in patients with recurrent urolithiasis
      stratified according to age and gender.
AB  - OBJECTIVE: Little is known regarding the metabolic features associated with aging
      and gender in urolithiais patients. We compared the metabolic characteristics
      among 3 generations (young, middle-aged and old) with recurrent calcium
      containing urinary stones. METHODS: One hundred and eighty-one patients with
      recurrent calcium-containing stones, including 71 patients aged </=45 years
      (group 1), 71 patients aged 46-60 years (group 2) and 39 patients aged >/=61
      years (group 3), were investigated by metabolic evaluation. The frequencies of
      metabolic abnormalities, the value of each urinary constituent and the
      supersaturation index (AP(CaOx) index) were compared among subgroups of the 3
      generations, containing both males and females. RESULTS: The number of metabolic
      abnormalities was the greatest in group 1, followed by group 2 and group 3.
      Hyperoxaluria was the most common abnormality in each group. Group 1 females
      showed a lower frequency of hypocitraturia than group 3 females. This was the
      only characteristic that showed a significant difference between the groups.
      Urinary calcium excretion was significantly greater in group 1 than in group 3.
      Urinary citrate excretion and the AP(CaOx) index were significantly higher in
      group 1 than in group 3 in females. Male patients had a significantly higher
      number of metabolic abnormalities than female patients, especially in group 1.
      CONCLUSION: Multiple metabolic abnormalities, particularly a high calcium
      excretion appear to be crucial factors in the development and recurrence of
      urolithiasis in young patients. Low urinary citrate excretion could play an
      important role in the occurrence of urolithiasis in elderly females.

PMID- 10940704
TI  - ESWL in hemophiliac patients.
AB  - OBJECTIVE: To assess ESWL treatment of urolithiasis in patients with hemophilia,
      the frequency of hemorrhagic complications, and to determine the treatment
      outline. PATIENTS AND METHODS: From 1991 to 1997, eleven patients with hemophilia
      were treated by ESWL for urolithiasis. Substitution of deficient coagulation
      factors was started on the day of treatment. Ultrasound examination was performed
      in all cases on the 1st day after the procedure in order to discover any
      potential hemorrhagic complications. Substitution withdrawal depended on the
      patients' general status, lack of hematuria and the absence of signs of
      hemorrhage. Preliminary results were evaluated after 7-10 days on the basis of
      plain abdominal X-ray of the kidney, ureter and bladder and ultrasonography.
      RESULTS: In total, 25 ESWL sessions were performed, 1-6/patient. Nine patients
      (81.8%) discharged stones, and 2 patients are being followed up. No hemorrhagic
      complications were observed. CONCLUSIONS: Substitution of deficient coagulation
      factors makes ESWL a safe method of urinary stone management in hemophiliacs. No
      hemorrhagic complications were seen in our patients. Substitution withdrawal may
      be based on the patients' good general status, lack of hematuria and absence of
      signs of hemorrhage.

PMID- 10940705
TI  - Is conservative organ-sparing treatment of penile carcinoma justified?
AB  - PURPOSE: The results of different conservative organ-sparing methods -
      radiotherapy, chemotherapy and radiochemotherapy - in the treatment of penile
      carcinoma were studied. MATERIALS AND METHODS: Conservatively treated 223
      patients with penile carcinoma seen in three hospitals between 1959 and 1996
      years were studied retrospectively. Among them 155 received radiotherapy, 33
      chemotherapy, and 35 radiochemotherapy. RESULTS: The local control was achieved
      in 135 (60.5%) of 223 patients. The difference in local control rate among these
      three groups of patients has not reached statistical significance. The efficacy
      of conservative treatment was highly associated with three factors: tumor size,
      grade and patient's age. Overall, 24 of 135 patients (17.7%) had local
      recurrence. Ten patients (4.5%) developed regional metastases. The recurrence
      rate did not correlate with tumor size and grade and was similar for all
      treatment modalities. Long-term results of each method were approximatley equal
      and 5-year survival varied from 78 to 88%. CONCLUSION: Conservative organ-sparing
      treatment of early-stage penile carcinomas is justified. Failure should be
      corrected by surgery without compromising survival.

PMID- 10940706
TI  - Modified Ghoneim's technique using a single serous-lined extramural tunnel in
      detubularized orthotopic ileal W-bladder.
AB  - OBJECTIVES: We report our preliminary clinical experience with a modification of
      Ghoneim's original technique involving reimplantation of ureters in a single
      tunnel on the right part of the neobladder forming a 'W' shape. METHODS: From
      1997 to 1999, we performed radical cystectomy with double 'W' orthotopic
      neobladder construction and uretero-ileal reimplantation using our modified
      Ghoneim's technique on 11 male patients, aged 40-74 (mean 65.5) years, affected
      by invasive bladder cancer. RESULTS: No postoperative complications were
      observed. After a mean follow-up of 12.5 months all patients are free of
      recurrences. CONCLUSIONS: In our hands the modified Ghoneim's technique seems to
      reduce the mean operating time required to tailor the uretero-ileal anastomosis
      and guarantee greater stability of the anastomosis itself.

PMID- 10940707
TI  - Rectodynamic and radiological assessment in modified mainz pouch II cases.
AB  - OBJECTIVE: To evaluate the radiologic findings and to measure the pressure
      changes in a modified sigmoidorectal pouch (Mainz pouch II procedure). METHODS: A
      total of 26 patients who had a radical cystectomy because of muscle-invasive
      bladder tumor underwent a Mainz pouch II procedure between 1993 and 1998. The
      differences from the original definition was a reverse ureteral anastomosis and a
      detubularized segment at least 30 cm in length. In all cases, sigmoidoscopy was
      done and sigmoidal pressure and capacity were measured preoperatively and at the
      3rd and 6th months postoperatively besides the colon X-rays. The 24-hour pouch
      pressure changes called 'natural pouch pressure' was measured using a handmade
      system with a central venous pressure (CVP) manometer at the 3rd month
      postoperatively. RESULTS: Preoperative colon X-rays showed a passage of opaque
      substance through the descending colon at an average volume of 150 ml (average
      sigma capacity), whereas postoperative anteroposterior and oblique pouch X-rays
      showed no passage up to an average volume of 520 ml (270-650) though the
      descending colon. The sigmoidal colon pressure that was on average 20 cm H(2)O at
      the preoperative evaluation was measured as 6 cm H(2)O at the 3rd month and 6.5
      cm H(2)O at the 6th months during the postoperative period. 24 hour natural pouch
      pressure was found to be 8.7 cm H(2)O on average while the pressure was found to
      be 13.8 cm H(2)O on average when the patient felt abdominal discomfort, in other
      words the desire to defecat (miction). CONCLUSIONS: A modified sigmoidorectal
      pouch procedure not only provides a reservoir with a higher capacity and lower
      pressure without a reflux to the upper urinary tract and descending colon with
      lower metabolic acidosis problem, but it is also a good alternative diversion
      procedure that whould be preferable especially in Muslim countries as it does not
      cause any difficulties in terms of Islamic worship.

PMID- 10940708
TI  - Cellular distribution of retinoic acid receptor-alpha in benign hyperplastic and
      malignant human prostates: comparison with androgen, estrogen and progesterone
      receptor status.
AB  - OBJECTIVES: Retinoids are unique modulators of gene activity, cell growth and
      differentiation by binding to a series of nuclear receptors, i.e. all-trans
      retinoic acid receptors (RAR) or 9-cis-retinoid receptors (RXR). In this study,
      the expression of RARalpha was immunohistochemically evaluated in benign,
      hyperplastic and malignant prostatic tissue and correlated with sex steroid
      receptor status. METHODS: Twenty-four cases of BPH and 139 cases of primary
      prostatic carcinoma were evaluated for RARalpha expression in correlation with
      androgen (AR), estrogen (ER) and progesterone (PGR) receptor staining, as well as
      with tumor grade. RESULTS: RARalpha was detected in the nuclei of epithelial
      cells in both BPH and prostate carcinoma cases. A modest inverse relationship
      with grade was present, especially for grade I and grade II tumors. AR staining
      was intense and a strong inverse relationship with grade was revealed. Although
      ER and PGR showed nuclear staining in prostatic epithelium, the overall
      expression for these receptors was low. When RARalpha content was compared to the
      nuclear AR expression, at least two-fold higher RARalpha levels were observed in
      AR+ grade II and grade III tumors. CONCLUSIONS: RARalpha expression can be
      immunohistochemically evaluated in formalin-fixed paraffin-embedded prostatic
      tissue. RARalpha expression is significantly elevated in AR+ moderately and
      poorly differentiated prostate carcinomas. Immunohistochemical determination of
      RARalpha content may be useful in defining the patient subsets in which retinoid
      based treatment may be of clinical value.

PMID- 10940709
TI  - Alterations in expression of cadherin-6 and E-cadherin during kidney development
      and in renal cell carcinoma.
AB  - OBJECTIVES: Cell-cell adhesion mediated by cadherins is tight and stable and
      preserves tissue integrity. However, during tissue remodeling, e.g., development,
      adhesion may be modified for morphogenic movement. Similarly, during
      carcinogenesis, cell-cell adhesion might alter leading to a more aggressive
      phenotype. Here we describe cadherin expression patterns in developing, adult,
      and neoplastic kidney. METHODS: Fetal kidneys were obtained from voluntary
      terminations of pregnancy and 43 renal cell carcinomas (RCC) and normal kidneys
      were obtained at nephrectomy. Frozen sections of these specimens were stained
      immunohistochemically using antibodies against E-cadherin (ECD), cadherin-6
      (CAD6) and alpha-catenin (alpha-cat). RESULTS: CAD6 was expressed in lower and
      middle limbs of the S-shaped bodies, structures that will develop into renal
      proximal tubules, which also express CAD6. Similarly, ECD was expressed in the
      upper limb of S-shaped bodies, structures which will develop into distal and
      collecting tubules which also express ECD. Twenty-four out of 43 RCC (55.8%)
      displayed a CAD6 (+)/ECD (-)/alpha-cat (+) phenotype. The other RCC had a CAD6
      (+)/ECD (+)/alpha-cat (+) phenotype (10/43, 23.2%), CAD6 (-)/ECD (+)/alpha-cat
      (+) phenotype (3/43, 7.0%) or CAD6 (-)/ECD (-)/alpha-cat (+) phenotype (6/43,
      14.0%), respectively. On the other hand, normal, heterogeneous, or absent
      expression of CAD6 was seen in 19, 15, and 9 tumors, whereas in 11, 2, and 30
      tumors, respectively, ECD expression was seen. Survival curves showed that
      abnormal CAD6 expression correlated with a poor prognosis rather than abnormal
      ECD expression. CONCLUSIONS: The combination of cadherin expression appeared to
      be fixed relatively early during kidney organogenesis. Since almost all RCC
      originate from proximal tubular epithelial cells (CAD6 (+)/ECD (-)/alpha-cat
      (+)), only 55. 8% of RCC retained the original cadherin phenotype. Alterations in
      expression of these molecules may be a reflection of the degree of
      dedifferentiation from the primary organ. In addition, scoring of expression
      patterns including heterogeneous expression could be a useful tool to estimate
      the malignancy potential of the tumor.

PMID- 10940710
TI  - Local thrombolytic treatment for renal arterial embolism.
AB  - OBJECTIVE: To determine the utility of local thrombolysis in the treatment of
      acute renal arterial occlusion. METHODS: We used local thrombolytic treatment in
      a female patient, aged 76, with 72 h of anuria, right lumbar and flank pain. She
      had a 3-year history of ischemic heart disease and atrial fibrillation controlled
      with digital treatment. Also, she was nephrectomized on the left side 33 years
      ago for lithiasic pyonephrosis. A normal right urinary tract was demonstrated
      with ultrasound examination, KUB radiography and retrograde pyelography. The next
      step was diagnostic abdominal angiography and local thrombolytic treatment with
      streptokinase. RESULT: Thrombolysis with streptokinase was successful following
      72 h of renal artery occlusion. After 24 months the patient is doing well.
      CONCLUSION: Local intra-arterial thrombolysis is the treatment of choice in renal
      artery occlusion.

PMID- 10940711
TI  - Laparoscopic partial adrenalectomy for bilateral pheochromocytomas in a boy with
      von Hippel-Lindau disease.
AB  - OBJECTIVES: In adults, increasing numbers of adrenalectomies for
      pheochromocytomas are performed laparoscopically. We report for the first time
      laparoscopic bilateral subtotal adrenalectomy for pheochromocytomas in an 8-year
      old boy with von Hippel-Lindau disease. METHODS: In July 1998, an 8-year-old boy
      with von Hippel-Lindau disease underwent laparoscopic adrenal-sparing surgery for
      bilateral pheochromocytomas. The boy presented with severe hypertension and two
      pheochromocytomas on both sides. RESULTS: The child could be solely treated with
      laparoscopic adrenal-sparing surgery. The procedure was completed as planned.
      There were absolutely no intraoperative or postoperative complications.
      Postoperatively, catecholamine levels and hypertension went back to normal. At
      follow-up no residual tumor could be detected and no steroid replacement therapy
      was necessary. CONCLUSIONS: In experienced hands, laparoscopic adrenal-sparing
      surgery for pheochromocytomas is feasible and safe. Moreover, this minimal
      invasive approach represents an exceptional improvement in life quality,
      especially in children with von Hippel-Lindau disease since surgery will probably
      be necessary again and again in their future life.

PMID- 10940712
TI  - Massive bilateral renal and perirenal hemorrhage due to polyarteritis nodosa: a
      life-threatening urologic condition.

PMID- 10940713
TI  - Historical aspects of the treatment of urinary incontinence.
AB  - Ancient reports on urinary incontinence are rather rare and mainly address cases
      of extraurethral incontinence, e.g. due to a fistula acquired during childbirth
      or overflow incontinence, e.g. in males with urinary retention or after spinal
      cord injury. In modern times several authors dealt with the problem of
      postoperative incontinence after perineal lithotomy. Surgical techniques for the
      cure of urinary incontinence were not introduced before the 19th century. First
      this was limited to fistula repair but at the turn of the century new procedures
      for stress incontinence were introduced and became standard clinical procedures.
      Other modern techniques, e.g. artificial sphincters or electrostimulation, were
      alternatives developed in urology during the second half of our century. This
      article from the history of medicine outlines early reports on urinary
      incontinence and reveals a more detailed review of the different treatment
      options including conservative therapies, incontinence devices, electrotherapy
      and surgical procedures, including injection therapies and artificial sphincters.

PMID- 10940714
TI  - Urological Laparoscopy for Beginners.

PMID- 10940716
TI  - The genetics of systemic lupus erythematosus.
AB  - BACKGROUND: There is a genetic predisposition to human systemic lupus
      erythematosus (SLE). The genes that contribute to susceptibility are, for the
      most part, unknown. The introduction of new gene mapping techniques has opened
      the way to explore lupus genetics on a genome-wide basis. METHODS:
      Microsatellites are simple sequence repeats widely distributed throughout
      eukaryotic genomes. They exhibit length variation. This polymorphism can be
      exploited to provide a panoply of genome-wide markers. Thereby, loci linked with
      lupus have been mapped in lupus-prone mouse strains and in recently published
      studies in multi-case human families. RESULTS: More than 20 non-MHC (major
      histocompatibility complex) loci have now been linked with murine lupus. Nine non
      MHC loci have been corroborated in human SLE. Some of the mouse intervals are
      syntenic with human loci raising the tantalizing possibility of common
      susceptibility genes. Although we await the results of formal gene
      identification, functional studies in back-cross and congenic analyses indicate
      that, in the mouse at least, disease genes act at multiple levels in disease
      development. CONCLUSIONS: A large number of genes are involved in the
      pathogenesis of SLE. The data also suggest that even the MHC contribution is
      multiple. Having mapped disease loci, geneticists now face the task of closing
      down on the actual aetiological alleles and demonstrating how they might operate.
      This undertaking will add significantly to our understanding of disease
      development.

PMID- 10940715
TI  - Murine models of renal disease: possibilities and problems in studies using
      mutant mice.
AB  - The elucidation of the pathogenesis of human renal disease at the molecular level
      has been facilitated by the growing field of gene targeting and the development
      of mouse strains with single-gene deletions - the 'knock-out' mice. Experimental
      nephrology, therefore, requires well-characterized and reliable models of human
      renal disease that can be induced reproducibly in mice. Today surgical procedures
      for the induction of renal ischemia, chronic renal failure, and ureter
      obstruction are feasible in mice. Models of mesangioproliferative or crescentic
      glomerulonephritis, glomerulosclerosis, and tubulointerstitial disease are
      readily available; however, these depend heavily on the mouse genetic background.
      Attention to the genetic background and appropriate backcrossing are, therefore,
      of great importance in the design and interpretation of experimental studies,
      especially in transgenic mice. Simple murine models displaying the clinical
      features of other human renal diseases such as IgA nephropathy, membranous
      glomerulonephritis, and renal vasculitis are still lacking. Mouse strains that
      spontaneously develop distinct renal pathologies similar to lupus nephritis and
      focal-segmental glomerulosclerosis can be intercrossed with transgenic mice to
      study the impact of single-gene deletions on the renal phenotype. The present
      review provides a survey about currently available spontaneous and inducible
      murine models of renal disease with special attention to problems and future
      perspectives for their use in transgenic animals.

PMID- 10940717
TI  - Immunological function of tubular epithelial cells: the functional implications
      of CD40 expression.
AB  - Tubulo-interstitial inflammation in the kidney is characterized by the presence
      of activated T cells. Both by the local production of cytokines, as well as by
      direct cell-cell interactions, these activated T cells might affect the immune
      and inflammatory response. Recently it has been demonstrated that these kidney
      infiltrating T cells express CD40 ligand and that tubular epithelial cells (TECs)
      express CD40. In the present review we will discuss the potential implications of
      CD40-CD40L interactions for the activation of TECs and its immunological
      function.

PMID- 10940718
TI  - Polycystin expression in the kidney and other tissues: complexity, consensus and
      controversy.
AB  - PKD1, the major gene mutated in autosomal dominant polycystic kidney disease, was
      identified in 1994, and fully sequenced in 1995. The protein which it encodes,
      polycystin-1, is the first member of a new family of proteins, whose functions
      presently remain unclear. This review seeks to highlight the difficulties
      researchers studying polycystin-1 have faced and to summarize the current areas
      of consensus and controversy between different groups, particularly with regard
      to the expression pattern, subcellular location and biochemical characterization
      of polycystin-1. Where relevant, more recent data regarding polycystin-2, the
      protein encoded by PKD2, will also be discussed.

PMID- 10940719
TI  - Cell-specific expression of the IP(3) receptor gene family in the kidney.
AB  - BACKGROUND/AIM: The localization of inositol trisphosphate (IP(3)) receptor
      isoforms, types 1-3, in the kidney and their role in the regulation of the
      intracellular calcium concentration - [Ca(2+)](i) - are discussed. METHODS:
      Immunohistological studies with isoform-specific antibodies were performed to
      reveal the localization of IP(3) receptor isoforms. To examine the role of IP(3)
      receptor type 1 in the glomeruli, the responses of [Ca(2+)](i) to hormonal
      stimuli were examined in IP(3) receptor type 1 knockout mice. RESULTS: In the
      immunohistological study, type 1 receptor was present in arteries, afferent
      arterioles, and mesangial cells. Double staining with antibodies against
      aquaporin 2 and IP(3) type 2 receptor revealed that type 2 receptor was localized
      mainly in the intercalated cells. The type 3 receptor showed characteristic
      intracellular localization in the collecting duct cells of the cortex to the
      outer medulla. Immunostaining of type 3 receptor was most intense in the
      cytoplasm on the basolateral membrane side and was not seen on the apical side.
      The responses of [Ca(2+)](i) to angiotensin II and endothelin in the glomeruli
      were markedly attenuated in IP(3) receptor type 1 knockout mice. CONCLUSIONS: The
      three isoforms of the IP(3) receptor showed distinctive localization in the
      kidney, and the type 1 receptor plays a major role in the regulation of
      [Ca(2+)](i) in the glomeruli. The physiological significance of the cell-specific
      localization, however, remains to be determined.

PMID- 10940720
TI  - Retinoids and renal development.
AB  - Although it has long been appreciated that retinoids play an essential role in
      kidney organogenesis, it has only recently been recognized that even mild fetal
      vitamin A deficiency syndromes can result in a reduction in nephron number.
      Recent studies have also begun to define the cellular and molecular events
      associated with retinoid actions in the fetal kidney and have demonstrated the
      essential function of retinoids in branching growth of the ureteric bud.
      Importantly, characterization of the renal developmental effects of RAR
      alpha/beta 2 double homozygous mice combined with metanephric organ culture
      studies have together shown that one essential function of retinoid action in the
      developing kidney is the maintenance of c-ret expression in the tips of the
      ureteric bud. However, many other potential retinoid target genes including
      midkine, sonic hedgehog, Hox d-11, matrix metalloproteinases, and tissue
      inhibitors of metalloproteinases appear to play important roles in renal
      development and might be important downstream mediators of retinoid effects in
      the developing kidney. It can, therefore, be anticipated that important new
      insights into fetal kidney development will be forthcoming in the near future, as
      the essential target genes affected by retinoid signal transduction are
      progressively elucidated.

PMID- 10940721
TI  - Immune recognition of glomerular antigens.
AB  - Autoimmunity is thought to cause most varieties of glomerulonephritis including
      membranous nephropathy, minimal-change nephropathy, Goodpasture's disease and
      possibly IgA nephropathy. Much effort has been and is directed at understanding
      the mechanisms of immune system driven inflammation and of the consequent renal
      injury and repair or scarring. The purpose of this article is to focus attention
      on the way the immune system recognizes kidney autoantigens, a process that must
      be a pivotal in the initiation of autoimmune kidney disease.

PMID- 10940722
TI  - Renal expression of two 'thyroid-specific' genes: thyrotropin receptor and
      thyroglobulin.
AB  - Numerous renal abnormalities accompany thyroid disease, most of which have been
      ascribed to the effects of thyroid hormone on renal metabolism. In the present
      report, we investigate the renal expression of the nominally thyroid-specific
      proteins, thyroid-stimulating hormone (TSH) receptor (TSHR) and thyroglobulin
      (Tg), as potential links between renal and thyroid function. The expression of
      TSHR has been identified in several extrathyroidal tissues, but its presence in
      the kidney remains controversial. We have used reverse-transcriptase polymerase
      chain reaction and DNA sequencing to demonstrate the presence of TSHR transcript
      in human and mouse kidney, in a primary culture of human kidney, and in a green
      monkey kidney epithelioid cell line. Furthermore, human kidney cells responded to
      TSH with a 2.5- fold increase in intracellular cyclic adenosine monophosphate,
      suggesting the presence of functional TSHR protein. Comparison of renal
      expression of TSHR in a bovine growth hormone transgenic mouse model of
      progressive glomerulosclerosis with control mice suggested increased TSHR
      transcript in the renal cortex of transgenic animals. TSHR transcript was also
      detected in mouse mesangial cells in vitro which responded to TSH with
      significant increases in the formation of three-dimensional hillhocks. Polymerase
      chain reaction also confirmed the presence of Tg transcript in human and mouse
      kidneys and in mouse mesangial cells, but no effect of either TSH or cyclic
      adenosine monophosphate on Tg transcript levels could be discerned.
      Immunofluorescent staining with a monoclonal anti-Tg antibody identified positive
      staining in the cytoplasm of mesangial cells. These data suggest that the kidney
      is capable of expressing the thyroid-specific genes, TSHR and Tg, which could
      conceivably mediate effects of thyroid disease in the kidney.

PMID- 10940723
TI  - Virulence factors of Escherichia coli contribute to acute renal failure.
AB  - BACKGROUND: The development of acute renal failure (ARF) significantly enhances
      the mortality of patients with Gram-negative septic shock. The role of specific
      bacterial virulence factors different from lipopolysaccharides (LPS) in the
      deterioration of renal function in septic shock remains to be determined.
      METHODS: An Escherichia coli wild-type strain (536/21 WT, O6:K15:H31) was
      isolated from a patient suffering from a urinary tract infection. The strain
      expresses various virulence factors (e.g. hemolysin, fimbriae) genetically
      encoded by pathogenicity islands. The spontaneous deletion mutant 536/21 Del
      lacks the expression of these virulence factors. Isolated rat kidneys were
      perfused with a suspension (5 x 10(4)/ml) of the respective strain or control
      perfusion medium and the renal functional parameters were analyzed. Intrarenal
      deposition of E. coli was detected by immunohistology and Gram staining. RESULTS:
      The perfusion of the isolated perfused rat kidney with a uropathogenic E. coli
      wild-type strain (536/21 WT) caused an acute deterioration of renal function
      which was not observed in kidneys exposed to a deletion mutant of E. coli 536/21
      lacking the expression of virulence factors. The glomerular filtration rate and
      the urine flow rate significantly decreased only in kidneys perfused with the E.
      coli wild-type strain, while there was no change versus controls in kidneys
      perfused with the deletion mutant. CONCLUSIONS: Distinctive bacterial virulence
      factors different from LPS such as hemolysin and the presence of different
      fimbriae may contribute to the development of ARF in sepsis induced by E. coli.
      Anti-LPS strategies may not be sufficient to reduce the risk of ARF in Gram
      negative septic shock.

PMID- 10940724
TI  - Cellular localization of aquaporin 7 in the rat kidney.
AB  - The cDNA for the seventh mammalian aquaporin (AQP7) was isolated from rat testis,
      and its expression was demonstrated at the tail of late spermatids [Ishibashi et
      al: J Biol Chem 1997;272:20782-20786]. AQP7 is also expressed in the kidney. The
      localization of AQP7 in the kidney is unknown. We examined the cellular
      localization of AQP7 in the kidney with Northern blot, reverse transcribed PCR,
      Western blot and immunohistochemistry in the rat kidney. In Northern blot, AQP7
      was expressed in the cortex and the outer medulla but absent in the inner medulla
      of the kidney. Reverse transcribed PCR of rat nephron segments revealed the
      selective expression of AQP7 at the proximal straight tubules (PST). Western blot
      of the membrane fraction of outer medulla revealed a single band of approximately
      33 kDa. Immunohistochemistry of the rat kidney showed the selective expression of
      AQP7 at the brush border membranes of PST (S3 segment). AQP7 is now shown to be
      localized selectively at the brush border membranes of PST in the rat kidney. The
      result suggests that AQP7 may function as a pathway for transcellular water
      transport in PST in concert with more widely expressed AQP1 in proximal tubules.
      Alternatively, as AQP7 transports urea as well as water, AQP7 may function as a
      passive urea secretory pathway in this segment and may play a role in the
      formation and/or maintenance of the medullary urea concentration gradient.

PMID- 10940725
TI  - Reciprocal regulation of LTA(4) hydrolase expression in human monocytes by gamma
      interferon and interleukins 4 and 13: potential relevance to leukotriene
      regulation in glomerular disease.
AB  - BACKGROUND/AIMS: Leukotriene A(4) (LTA(4)) hydrolase catalyzes the final step in
      the synthesis of leukotriene B(4) (LTB(4)). TH-1- and TH-2-derived cytokines may
      regulate LTB(4) synthesis by monocytes through their actions on the expression of
      LTA(4) hydrolase. METHODS: Freshly isolated monocytes were incubated with pro-
      and anti-inflammatory cytokines for 36 h. mRNA expression was determined by
      Northern blot, protein expression was determined by Western blot and LTB(4)
      synthesis was determined by ELISA. RESULTS: Interferon-gamma (a TH-2-derived
      cytokine) increased significantly LTA(4) hydrolase mRNA expression, whereas
      interleukin (IL)-4 and IL-13 (both TH-2-derived cytokines) decreased LTA(4)
      hydrolase mRNA expression in these cells. The same effects were seen on the
      expression of immunoreactive LTA(4) hydrolase after incubating the monocytes with
      either TH-1- or TH-2-derived cytokines. The monocyte-derived cytokine IL-1 beta
      did not show any significant effect on LTA(4) hydrolase mRNA expression. When
      LTB(4) release was measured, both IL-1 beta and interferon-gamma significantly
      increased LTB(4) production by monocytes, while TH-2 cytokines (IL-4 and IL-13)
      decreased it. CONCLUSION: The opposing effects of TH-1- and TH-2-derived
      cytokines on the expression of LTA(4) hydrolase mRNA may regulate LTB(4)
      synthesis by monocytes during inflammation.

PMID- 10940726
TI  - Endotoxin-induced renal failure. I. A role for altered renal microcirculation.
AB  - The pathogenesis of sepsis-induced renal failure is multifactorial and only
      partially understood. In these studies we evaluated intrarenal microcirculatory
      changes during endotoxemia and the potential role of nitric oxide (NO) and
      endothelin in these changes. In anesthetized rats endotoxin infusion
      [lipopolysaccharide (LPS), Escherichia coli serotype 0127:B8; 10 mg/kg/h]
      resulted in hypotension and a transient enhancement of renal blood flow, with
      cortical vasodilation and a loss of outer medullary vasodilatory response to
      hypotension. The initial cortical vasodilation was abolished by the NO synthase
      inhibitor NG-nitro-L-arginine methyl ester, but not by indomethacin. Direct NO
      measurements disclosed a gradual rise in cortical NO, despite the waning
      vasodilatory effect, suggesting antagonizing vasoconstrictive stimuli. In rats
      pretreated by LPS (1 mg/kg i.p. 1 day earlier) the renal blood flow was reduced
      to 55% of that of controls. Moreover, the vasodilatory response to LPS infusion
      was converted into profound cortical and medullary vasoconstriction. In these
      preconditioned rats the endothelin receptor antagonist bosentan evoked a
      vasodilatory response and attenuated the vasoconstrictive reaction to LPS
      infusion. The infusion of another LPS (E. coli serotype 0111:B4) exerted
      predominant and protracted renal vasodilation without hypotension. In conclusion,
      different LPS exert diverse systemic and renal hemodynamic responses. The 0127:B8
      serotype attenuates renal medullary vasodilation during hypotension, exerts
      transient cortical vasodilation, and following repeated exposure induces profound
      renal vasoconstriction. NO and endothelin participate in LPS-induced vascular
      responses that may predispose to hypoxic tubular damage.

PMID- 10940727
TI  - Endotoxin-induced renal failure. II. A role for tubular hypoxic damage.
AB  - Endotoxin-induced hypotension and altered renal microcirculation could lead to
      tubular injury, particularly at the physiologically hypoxic outer medulla. We
      explored this hypothesis in isolated perfused kidneys and in vivo in rats
      subjected to endotoxemia. Rat kidneys were removed 15 min after endotoxin
      injection in vivo (from Escherichia coli 0127:B8, 1 mg/kg i.p.) and perfused with
      oxygenated medium supplemented with 20 amino acids and endotoxin. Glomerular
      filtration rate and filtration fraction markedly declined (0.4 +/- 0. 1 ml/min
      and 1.1 +/- 0.1, respectively) as compared with control kidneys (0.7 +/- 0.1
      ml/min and 1.8 +/- 0.1, n = 8-12 per group; p < 0.05). Hypoxic injury to
      medullary thick ascending limbs in the innermost outer medulla increased (47 +/-
      9% of tubules vs. 16 +/- 8% in controls, p < 0.05). When rats were preconditioned
      with an additional endotoxin injection 16 h earlier (a manipulation that markedly
      reduces cortical and medullary blood flow), glomerular filtration rate and
      filtration fraction further declined to 0.1 +/- 0.0 ml/min and 0.4 +/- 0.1,
      respectively (p < 0.01), and tubular sodium reabsorption fell to 81 +/- 12 vs 98
      +/- 0% in controls (p < 0.05). Tubular damage, however, did not increase (20 +/-
      7%), probably reflecting a decline in reabsorptive workload and oxygen
      requirement. In rats subjected to a single or two repeated daily doses of
      endotoxin (1 mg/kg i.p.) plasma creatinine comparably rose 41% on the average
      over 24 h, creatinine clearance fell by 27% (p < 0.0001), but tubular damage was
      absent. By contrast, in rats preconditioned with indomethacin and the nitric
      oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (10 mg/kg), the
      addition of endotoxin markedly augmented outer medullary hypoxic tubular damage
      both in S(3) segments (27 +/- 10 vs 1 +/- 1%) and in medullary thick ascending
      limbs (38 +/- 11 vs. 10 +/- 5%, n = 7-8; p < 0.05). It is concluded that under
      special conditions, such as altered medullary oxygen balance or defective nitric
      oxide or prostaglandin synthesis, endotoxin may predispose to hypoxic outer
      medullary tubular damage.

PMID- 10940728
TI  - Improved recovery following posttransplant acute renal failure in rat renal
      isografts with an oral endothelin-A receptor antagonist.
AB  - BACKGROUND: Delayed renal function after transplantation is a strong predictor of
      long-term graft survival. As an increased expression of endothelin (ET) has been
      demonstrated during ischemia/reperfusion injury, we hypothesized that ET-A
      receptor blockade could improve the recovery of acute renal failure in a rat
      model of isogeneic kidney transplantation. METHODS: Kidneys of Fisher (F344,
      RT1(1v1)) rat donors flushed with cooled University of Wisconsin solution were
      transplanted into bilaterally nephrectomized Fisher rats. Recipient animals were
      treated orally either with vehicle or the selective ET-A receptor antagonist
      LU135252 (30 mg/kg/day p.o.) for 14 days. Unilaterally nephrectomized Fisher rats
      not subjected to ischemia served as controls. No immunosuppression was given. On
      days 2, 6 and 14, metabolic studies were performed to evaluate endogenous
      creatinine clearance, fractional sodium excretion, and urinary endothelin
      excretion. Kidneys were harvested at the end of the experiment for determination
      of renal ET content and immunohistochemical assessment. RESULTS: Urinary ET
      excretion was increased in vehicle-treated isografts compared to
      uninephrectomized controls after 14 days. Treatment with LU135252 resulted in a
      significant improvement in creatinine clearance and fractional sodium excretion
      to the level of uninephrectomized rats after 14 days. Isografts treated with
      selective ET-A receptor blockade demonstrated a marked reduction in cell surface
      markers for macrophages/monocytes, T cells, MHC-II, and ICAM-1. CONCLUSION:
      Treatment with the selective ET-A receptor antagonist LU135252 accelerates
      recovery of renal function after isogeneic renal transplantation and attenuates
      cellular graft infiltration. This effect could have major implications for the
      treatment of patients undergoing renal transplantation, as an improved initial
      renal function may delay the onset of chronic allograft rejection.

PMID- 10940729
TI  - Sublytic complement injury does not activate NF-kappa B, or induce mitogenesis in
      rat mesangial cells.
AB  - Sublytic complement injury to glomerular mesangial cells, mediated by the
      terminal membrane attack complex of complement (C5b-9), is a potential initiating
      mechanism in IgA nephropathy. Sublytic complement injury has been reported to
      result in the production of a variety of pro-inflammatory molecules and growth
      factors, including many regulated by the transcription factor NF-kappa B. To
      determine the importance of complement injury in the pro-inflammatory signalling
      which occurs in IgA nephropathy, we investigated NF-kappa B activation following
      sublytic complement injury to cultured rat glomerular mesangial cells (RMCs). A
      sublytic dose of rabbit anti-Thy 1.1 (THY) serum and normal human serum was
      selected based upon flow cytometry, chromium-release assay, and induction of
      superoxide production. No significant C5b-9-induced NF-kappa B activation was
      detected by electrophoretic mobility shift assays, luciferase activity of RMCs
      transfected with a NF-kappa B-driven luciferase reporter construct, nor by
      Northern blots for the NF-kappa B-responsive mRNA species monocyte
      chemoattractant protein-1 or I kappa B alpha. Furthermore, measurements of (3)H
      incorporation following sublytic complement injury showed inhibition of mesangial
      cell mitogenesis in comparison to the heat-inactivated serum treatment and to THY
      alone. The results of this study suggest that sublytic complement injury to RMC
      does not directly activate NF-kappa B nor induce mesangial cell proliferation in
      mesangial cells. Other mechanisms such as IgA immune complex formation must be
      required to produce these events in IgA nephropathy.

PMID- 10940730
TI  - Prepubertal rats are more resistant to ischemic renal injury and recover more
      rapidly than adult rats.
AB  - Bilateral clamping of renal pedicles during 60, 75 or 90 min was used to
      characterize the evolution of ischemic acute renal failure (ARF) in prepubertal
      rats. To verify the existence of age-conditioned differences in the evolution of
      ARF, adult rats were exposed to 40, 60 or 75 min of clamping. After 7 days,
      survival rate was significantly better in young than adult rats for identical
      times of clamping (89 vs. 35% for 60 min and 69 vs. 35% for 75 min). Young rats
      largely died within the first 24 h following ischemia while the risk of death
      extended until the 4th day after ischemia in adult rats. Peak values of serum
      urea nitrogen and creatinine were observed on the 1st and 3rd day after ischemia
      in young and adult rats, respectively. In young rats, these markers of renal
      function returned to normal on days 5 and 6 whereas they remained elevated at the
      end of the study in adult animals. Growth curves of young rats paralleled those
      of sham-operated animals from the 3rd day of clamping whereas adult rats did not
      even reach the initial weight at the end of the study. Analysis of kidneys
      obtained 7 days after clamping revealed more severe histopathological lesions in
      adult rats as well as a higher proliferative activity (10-40 times the value of
      sham-operated animals versus 2-4 times the control value in young rats). Our
      findings indicate that kidneys from young rats are more resistant to ischemia and
      recover more quickly from the ischemic insult. Therefore, the experimental model
      of ischemic ARF is clearly different in young and adult rats.

PMID- 10940731
TI  - Isolated juxtaglomerular apparatus as a tool for exploring glomerular
      hemodynamics: application of microperfusion techniques.
AB  - The balance of the vascular tone between afferent and efferent arterioles (AAs
      and EAs, respectively) is a crucial determinant of glomerular hemodynamics. Thus,
      it is important to study the mechanisms that control their vascular tone to
      understand renal physiology and pathophysiology. In order to directly study the
      mechanisms that regulate their vascular tone, we have developed several in vitro
      microperfusion preparations of these arterioles, which have the advantage of
      allowing us to observe the arteriolar diameter directly in the absence of
      systemic hemodynamic and hormonal influences. In the AA but not EA, we have
      directly demonstrated the presence of two intrinsic mechanisms, namely the
      myogenic response and macula densa-mediated tubuloglomerular feedback, that play
      an important role in the control of vascular tone. We also found that both
      mechanism-induced constrictions of AAs can be modulated by endogenous nitric
      oxide. In addition, several humoral factors (such as angiotensin II or
      prostaglandins) play an important role in the control of AA tone. On the other
      hand, angiotensin II is one major factor that controls the vascular tone of the
      EA. We have found that the vasoconstrictor effect of angiotensin II on EAs is
      modulated by prostaglandins produced by the upstream glomerulus. Thus, this may
      be a mechanism whereby the glomerulus controls its own capillary pressure by
      releasing prostaglandins and thereby adjusting the resistance of the downstream
      EA. These varying mechanisms regulating AA and EA tone play an important role in
      the precise control of glomerular hemodynamics.

PMID- 10940732
TI  - Sensitive analysis of apoptosis using confocal laser scan microscopy.
AB  - Application of the TUNEL method and immunostaining cell-specific markers to a
      whole isolated glomerulus in combination with confocal laser scan microscopy can
      be used to analyze cell turnover including apoptosis within glomeruli.
      Furthermore, the technologies can be used to deepen our understanding of
      glomerular cell biology and pathophysiology at the cellular and molecular levels.

PMID- 10940733
TI  - Prolactin gene disruption does not compromise differentiation of
      tuberoinfundibular dopaminergic neurons.
AB  - In mice with spontaneous mutations in transcription factors Prop-1 or Pit-1, the
      pituitary fails to produce prolactin (PRL), GH and TSH, and numbers of
      hypothalamic PRL-regulating dopaminergic (DA) neurons (area A12) are reduced by
      more than 50%. A normal neuronal population can be maintained in these mutants by
      PRL treatment of neonates, but not of adults. Targeted disruption of the PRL
      structural gene in mice provides a new model of isolated PRL deficiency to test
      the specificity of the PRL neurotrophic effect. The present study used
      morphological methods to assess hypophysiotropic tuberoinfundibular dopaminergic
      (TIDA) neurons in these mice, with the hypothesis that isolated PRL deficiency
      also would lead to reduction in TIDA neuron number. Brains of female and male
      homozygous PRL-null (- or -) mice and normal heterozygous (+ or -) siblings were
      compared using formaldehyde-induced endogenous catecholamine fluorescence and
      tyrosine hydroxylase (TH) immunocytochemistry. Immunostaining intensity was
      quantified using computerized image analysis, and total numbers of TH
      immunoreactive neurons were counted in three diencephalic DA brain regions.
      Intensity of DA fluorescence in A12 perikarya and median eminence (ME) was
      reduced in - or - mice; fluorescence in other brain areas was comparable for - or
      - and + or - mice. Immunostaining intensity of TH was significantly lower (p =
      0.0001) in - or - than in normal mice in perikarya of A12, but not in cell bodies
      of nonhypophysiotropic area A13 (medial zona incerta). In external ME, TH
      immunostaining intensity was lower (p = 0.0001) in PRL-null than in normal mice.
      The decrease in TH intensity in both perikarya and in ME was significant for both
      female and male - or - mice. However, numbers of A12 neurons in the PRL-null mice
      were not lower than those of normal siblings. TH-immunoreactive cell number also
      did not differ between + or - and - or - mice in areas A13 and periventricular
      A14. The presence of a normal complement of A12 DA neurons in the PRL-null mice,
      despite greatly reduced DA and TH, emphasizes that steady-state content and
      differentiation of phenotype in individual neurons are very different
      assessments. The results suggest that, although absence of the stimulatory PRL
      feedback signal results in diminished activity of TIDA neurons, differentiation
      of these cells is not adversely affected.

PMID- 10940734
TI  - An endogenous serotonergic rhythm acting on 5-HT(2A) receptors may be involved in
      the diurnal changes in tuberoinfundibular dopaminergic neuronal activity and
      prolactin secretion in female rats.
AB  - The central serotonergic system has long been known to have a stimulatory role on
      the secretion of prolactin (PRL). The integrity of serotonergic neurotransmission
      is essential for the expression of the estrogen-induced afternoon PRL surge.
      Whether its effect on PRL involves change in the activity of tuberoinfundibular
      dopaminergic (TIDA) neurons has not been ascertained. In adult ovariectomized
      rats treated with estrogen, depletion of central serotonin (5-HT) by 5,7
      dihydroxytryptamine (5,7-DHT, 200 microg/rat, i.c.v.) effectively prevented the
      afternoon fall in TIDA neuronal activity (using the levels of 3,4
      dihydroxyphenylalanine and 3, 4-dihydroxyphenylacetic acid (DOPAC), and the ratio
      of DOPAC/dopamine in the median eminence as indices), and blunted the afternoon
      PRL surge. A single injection of a 5-HT(2A) receptor antagonist, ketanserin (5
      mg/kg, i.p. at 12.00 h), also had the same effects on the diurnal changes in TIDA
      neuronal activity and PRL secretion as the treatment with 5,7-DHT did.
      Intracerebroventricular injection of a 5-HT(2) receptor agonist 2, 5-dimethoxy-4
      iodoamphetamine (DOI) in the morning inhibited the TIDA neuronal activity and
      stimulated PRL secretion in a dose-dependent manner; while injection of a 5-HT(1)
      agonist, 8-hydroxy-dipropylaminotetralin, was without effect. Injection of DOI in
      5,7-DHT-pretreated rats at 14.30 h also lowered the TIDA neuronal activity and
      reinstated the PRL surge. In all, endogenous 5-HT, acting through the 5-HT(2A)
      receptor, appears to exhibit an inhibitory effect on TIDA neuronal activity
      during the afternoon, which is essential for the PRL surge.

PMID- 10940735
TI  - Involvement of endogenous opioidergic neurons in modulation of prolactin
      secretion in response to mating in the female rat.
AB  - Mating in female rats induces an acute prolactin (PRL) release within 60 min and
      twice-daily surges of PRL throughout the first 10 days of pregnancy to maintain
      luteal function. Little is known about the brain mechanism whereby the
      vaginocervical stimulation is processed to induce PRL release. Our recent results
      revealed an increase in Fos expression in the arcuate nucleus (ARC) following
      mating in the intact estrous rat, suggesting that a neuronal network in the brain
      area may participate in conveying and integrating the genitosensory stimulation.
      To further investigate the phenotype of activated neurons in the ARC, the present
      study examined whether beta-endorphin (beta-END) and/or dopamine (DA) neurons are
      activated by mating, and if so, whether activation is involved in the mating
      induced acute release of PRL and the establishment of the twice-daily surges of
      PRL. In experiment 1, proestrous rats receiving intromissions (mated group) from
      males or mounts without intromission (mounted group) were sacrificed along with
      rats taken directly from their home cage (control group) 60 min after the
      beginning of mating or mounting. Expression of Fos in beta-END neurons and
      expression of fos-related antigen (FRA) in DA neurons, which were labeled by
      tyrosine hydroxylase (TH) antibody in the ARC were examined by double-label
      immunocytochemistry. In experiment 2, proestrous females with indwelling atrial
      catheters were mated with males. Naloxone (10 microl/min, 2 mg/10 min), an opiate
      antagonist, or saline was infused before, during and after mating. Blood samples
      were collected during the mating session and also at several times 3 days after
      mating. The results showed that mating induced a significant increase in the
      percentage of beta-END/Fos colabeled neurons and a significant decrease in the
      number of beta-END cells in all subdivisions of the ARC. In contrast, neither the
      percentage of FRA/TH colabeled cells nor the number of TH cells was influenced by
      mating. Mating induced an acute increase in PRL release in saline-treated control
      animals within 30 min and a subsequent diurnal surge (18.00 h) and a nocturnal
      surge of PRL (2.00 h) 3 days after mating. Naloxone infusion during mating
      blocked the mating-induced acute PRL response and the diurnal surge of PRL 3 days
      after mating, but affected neither the nocturnal surge of PRL nor the incidence
      of pregnancy. These results demonstrate that (1) beta-END neurons but not DA
      neurons in the ARC are activated in response to mating in proestrous rats, and
      (2) the mating-induced activation of beta-END neurons may participate in the
      acute response of PRL release to mating and the memory mechanism for the
      establishment of the diurnal PRL surge, but not the nocturnal PRL surge in early
      pregnancy. These results lead to a conclusion that endogenous opioid peptides may
      be involved in the neuronal transmission of genitosensory stimulation to induce
      PRL secretion.

PMID- 10940736
TI  - Immunolocalization of androgen receptors and aromatase enzyme in the adult musk
      shrew brain.
AB  - In the brain and other tissues, estrogens are produced by aromatization of
      androgens. Biochemical data suggest that aromatase enzyme is regulated by the
      androgen receptor (AR). Neurons that contain either AR or aromatase (AROM) enzyme
      reside in many of the same brain regions. In this report, we examined the
      codistribution of AR- and AROM-enzyme-immunoreactive (-ir) neurons in several
      regions of the adult male and female musk shrew brain. Data were collected from
      the intermediate nucleus of the lateral septum (LS), medial anterior (BNSTMA) and
      medial posterointerior (BNSTMP) divisions of the bed nucleus of the stria
      terminalis, medial preoptic area (mPOA), ventromedial nucleus of the hypothalamus
      (VMN), medial (MeA), cortical and central nuclei of the amygdala. Males had
      significantly more AR-ir neurons in the BNSTMP, mPOA, VMN and LS as compared to
      females. With the exception of the BNSTMA and LS, males had more AROM-ir neurons
      in each region than females. Furthermore, males had significantly more double
      labeled neurons than females in the BNSTMP, mPOA, VMN, LS and MeA. The percentage
      of AROM-ir neurons that also contained AR immunoreactivity ranged from 13 to 82%
      depending on sex and region. The highest percentage of dual-labeled neurons (79%
      in females and 82% in males) was found in the VMN. Taken together, these data
      show that there is extensive cellular colocalization of AR and AROM enzyme in
      specific regions of the musk shrew brain. We propose that in both sexes, androgen
      receptors may act as transcription factors to regulate AROM enzyme.

PMID- 10940737
TI  - The effects of testicular denervation on spermatogenesis in the Sprague-Dawley
      rat.
AB  - In the rat, regression of spermatogenesis during the chronic stages of spinal
      cord injury (SCI) occurs in the presence of normal function of the pituitary
      testis hormone axis, thus suggesting that nonendocrine mechanisms might be
      involved. The current study examined whether disruption of neural input to the
      testis contributes to the cascade that leads to the regression of
      spermatogenesis. Four weeks after denervation of the superior spermatic nerve
      (SSN), testis weight was 25% lower (p < 0.01) than that of the contralateral sham
      operated testis. Defects in spermatogenesis including phagocytosis of mature
      spermatids, vacuolization of spermatid nuclei, delayed spermiation and incomplete
      cellular associations were observed in >60% of the tubules. In the remaining 30
      40% of tubules, the seminiferous epithelium was severely regressed. While cutting
      the inferior spermatic nerve (ISN) alone did not affect spermatogenesis
      significantly, it enhanced the effect of SSN denervation on both spermatogenesis
      and testis weight (p < 0.01). Spermatogenesis was totally regressed in the
      SSN/ISN-denervated testes. At this time, quantitatively normal spermatogonial
      proliferation was maintained in SSN- or ISN-denervated testes. Twelve weeks after
      surgery, regression of the seminiferous epithelium characterized by absence of
      proliferating spermatogonia, while undifferentiating spermatogonia were present,
      was observed in all SSN-denervated testes. At this time, regression of the
      seminiferous epithelia also occurred in >30% of the tubules in ISN-denervated
      testes. At both times, serum follicle-stimulating hormone, luteinizing hormone
      and testosterone levels were normal and >60% of normal testicular testosterone
      concentrations were maintained in the denervated testes. These results indicate
      that disruption of neural input to the testis is not a cause for the decrease in
      spermatogonial proliferation during the acute phase of SCI, but may contribute to
      the chronic effects of SCI on spermatogenesis.

PMID- 10940740
TI  - Role of leukocytes in the immunopathogenesis of ANCA-associated
      glomerulonephritis.

PMID- 10940739
TI  - Melatonin receptors in the pituitary of a teleost fish: mRNA expression, 2
      [(125)I]iodomelatonin binding and cyclic AMP response.
AB  - Melatonin has for a long time been involved in the photoperiodic control of fish
      physiology (growth, reproduction) and behavior (locomotor activity); but its
      mechanisms of action are not understood. We show here that 2
      [(125)I]iodomelatonin binds specifically to membrane preparations from Pike (Esox
      lucius, L.) pituitaries (K(D): 556 pM; B(max): 2.8 fmol/mg proteins).
      Radioautography indicated that the binding was restricted to a part of the
      pituitary only. Using polymerase chain reaction from pike genomic DNA, we
      subcloned two partial cDNAs encoding the P1.4 (Mel(1a)) and the P2.6 (Mel(1b))
      melatonin receptor subtypes. The two corresponding transcripts were expressed in
      the pituitary as revealed by RT-PCR assay and Southern blot hybridization. In
      culture, melatonin inhibited in a time- and dose-dependent manner cyclic AMP
      levels in pituitaries cultured in the presence of forskolin, an adenylyl cyclase
      activator. This is the first evidence for the expression of melatonin receptors
      and binding sites, and for the modulation of a second messenger by melatonin in
      the pituitary of a nonmammalian species. We suggest that in fish, the melatonin
      mediated photoperiodic control of neuroendocrine functions involves, at least, a
      direct effect on the pituitary.

PMID- 10940738
TI  - Vasoactive intestinal polypeptide and pituitary adenylate cyclase-activating
      polypeptides stimulate mitogen-activated protein kinase in the pituitary cell
      line GH4C1 by a 3',5'-cyclic adenosine monophosphate pathway.
AB  - Vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase
      activating polypeptide (PACAP38) regulate anterior pituitary cell secretion and
      proliferation. In the somatolactotrope GH4C1 cell line, these effects are
      mediated through the type-II-like PACAP receptor (VPAC2) coupled to the cAMP
      pathway. In this study, the control of the extracellularly responsive kinases
      (ERKs) by VIP and PACAP38 was investigated in GH4C1 cells. VIP and PACAP38
      increased ERK1 and ERK2 phosphorylation and were equipotent stimulators of both
      kinases. ERK activation was mimicked by cholera toxin, forskolin and 8bromo-cAMP.
      VIP and PACAP38 activation of ERK2 was blocked by the protein kinase A inhibitor
      H89, whereas the protein kinase C inhibitor GF109203X, or prior PMA-induced
      depletion of the protein kinases C, failed to inhibit VIP and PACAP38 activation
      of ERK2. In contrast, thyrotropin-releasing hormone (TRH) elicited ERK activation
      by a PKC-dependent process. ERK activation by VIP or PACAP38 and TRH were
      additive and both sensitive to the MEK inhibitors PD98059 and U0126. In parallel,
      U0126 reduced prolactin (PRL) mRNA levels induced by VIP. These results
      demonstrate for the first time that VIP and PACAP38 activate ERK in GH4C1 cells.
      Cyclic AMP increase is sufficient to elicit ERK activation in these cells and
      thus likely to represent the transduction pathway underlying VIP- and PACAP38
      dependent ERK activation. This mechanism seems to be involved in VIP-induced PRL
      gene regulation.

PMID- 10940741
TI  - Nonviral and viral gene transfer to the kidney in the context of transplantation.
AB  - BACKGROUND/AIMS: Local modulation of the immune response through genetic
      manipulation of the graft is an attractive novel approach to overcome the
      toxicity of immunosuppressive therapy to prevent acute graft rejection. We have
      previously reported that the cationic polymer polyethylenimine 25k (PEI 25k)
      transduced reporter genes when injected into the renal artery, but with a low
      transfection efficiency. Here we compare the risk/benefit profiles of such a
      nonviral versus a viral technique of gene transfer to the kidney in the context
      of renal transplantation. METHODS: Donor kidneys from Lewis rats were perfused in
      a closed circuit with an artificial cell-free medium containing PEI 25k complexed
      to an expression vector coding for the beta-galactosidase (beta-gal) gene and
      subsequently transplanted in a syngeneic animal. In a second set of experiments,
      donor kidneys were injected or perfused with a replication-deficient adenovirus
      encoding the beta-gal gene (AdCMV. beta-gal; 1 x 10(9) plaque-forming units)
      before transplantation. RESULTS: Perfusion of the kidney with PEI 25k/DNA
      complexes resulted in large areas of hypoperfusion characterized by injured
      glomeruli and tubuli, capillary thrombosis and accumulation of C3 in glomerular
      capillaries. Reperfusion of the kidney was achieved by lowering the PEI 25k/DNA
      ratio, but no detectable transfection was observed. In animals receiving
      adenovirus, the beta-gal activity increased with time and was localized mainly in
      proximal and distal tubular cells, as documented by beta-gal histochemistry and
      in situ hybridization. A significantly increased expression of beta-gal was
      achieved by perfusion of the kidney with AdCMV.beta-gal before transplantation,
      beta-gal staining mainly localizing in proximal and distal tubular cells.
      CONCLUSIONS: Unlike nonviral methods of gene delivery, adenovirus-mediated gene
      transfer to the kidney offers exciting perspectives for the development of
      molecular medicine in the field of organ transplantation.

PMID- 10940742
TI  - Association of polymorphic alleles of the calcium-sensing receptor gene with
      parathyroid hormone secretion in hemodialysis patients.
AB  - The present study was performed to investigate the association of calcium-sensing
      receptor (CaSR) genotypes with parathyroid hormone (PTH) secretion in
      hemodialysis patients. Subjects were 122 Japanese hemodialysis patients,
      including 39 patients with diabetes mellitus (DM). The CaSR polymorphisms tested
      were codon 990 in intracellular domain (A/A, A/G, and G/G groups) as well as T to
      C base change of intron 4 (T/T, T/C, and C/C groups). Statistical analysis of
      these polymorphisms revealed that the serum PTH level was significantly higher in
      the A/A group than in the G/G group in the former. In addition, the serum PTH
      level was also significantly higher in patients displaying C allele, as compared
      with the T/T group in the latter. This association of two polymorphisms with the
      serum PTH level was observed only in non-DM patients. Although two polymorphisms
      affected the PTH level independently, patients who possessed both genotypes
      (AAC+) had a markedly high level of PTH not only in the non-DM group but also in
      the DM group. The present findings indicate the possibility of the prediction for
      the extensive progression of secondary hyperparathyroidism through analyzing the
      CaSR polymorphisms in chronic hemodialysis patients.

PMID- 10940743
TI  - Assessing residual renal function and efficiency of hemodialysis--an application
      for urographic contrast media.
AB  - BACKGROUND: In patients on hemodialysis with end-stage renal disease there is an
      increasing interest in measuring both residual renal function (RRF) and quantity
      and quality of dialysis because insufficient dialysis gives higher mortality. For
      that purpose we have measured clearances of two urographic iodine (I) contrast
      media (CM) with different molecular masses (iohexol 821 u and iodixanol 1, 550
      u). These CM are filtered through glomeruli and dialysis membranes and have
      higher molecular masses than urea and creatinine and might represent the
      dialyzability of the hypothetic uremic toxins with a molecular mass of 300-5,000
      u. METHODS: Thirteen patients (8 of them were anuric) immediately after
      hemodialysis received 15 ml iohexol (300 mg I/ml i.v.) and 2 weeks later in the
      same way 15 ml iodixanol (320 mg I/ml). Nine other patients (2 anuric) received
      CM after only one dialysis; 8 got iohexol and 1 got iodixanol. After the CM
      injections the iodine concentrations were measured with X-ray fluorescence in
      blood and, when available, urine during the following 2 days including both the
      start and end of the next dialysis. Eighteen patients after two dialysis
      sessions, 2 weeks apart, received 10 ml iohexol i.v., and a single blood sample
      was taken at the start of the next dialysis 2 days later to determine RRF alone.
      RESULTS: In the 10 anuric patients the extrarenal clearances (mean +/- SD) were
      2.5 +/- 1.1 and 2.7 +/- 1.1 ml/min/1.73 m(2) for iohexol and iodixanol,
      respectively. In patients with RRF good correlations were demonstrated between
      body clearance, based on two blood samples, and renal clearance of CM. Good
      correlations (r(2) = 0.853 for iohexol, r(2) = 0.933 for iodixanol) were noted
      between two-sample and single-sample body clearances. Repeated single sample
      iohexol clearances gave a coefficient of variation of 15%. During dialysis the
      clearances of iohexol and iodixanol were, respectively, 69 +/- 16 and 58 +/- 11
      ml/min/1.73 m(2) when calculated from a single-pool model (hemodialysis clearance
      of CM from plasma). A median increase (rebound) of CM concentrations in plasma 45
      min dialysis was 8% for iodixanol and 18% for iohexol. When the CM concentration
      45 min after dialysis was used, the clearance values were by 8-10% lower and
      represented the hemodialysis clearance of CM from the extracellular compartments.
      The dialysis eliminations of iohexol and iodixanol were similar to that of urea,
      measured as percentage reduction of serum levels during dialysis. CONCLUSIONS: A
      single injection of CM at the end of dialysis followed by a single blood sample
      at the start of the next dialysis gives total body clearance, i.e., an estimation
      of the RRF. An additional blood sample at the end of the next dialysis gives
      dialysis efficiency.

PMID- 10940744
TI  - Effect of regional citrate anticoagulation on leukopenia, complement activation,
      and expression of leukocyte surface molecules during hemodialysis with unmodified
      cellulose membranes.
AB  - BACKGROUND: Dialysis with complement-activating membranes is associated with
      leukopenia, which is related to an increased expression of adhesion molecules on
      leukocytes. Citrate chelates calcium and has been claimed to attenuate
      leukopenia. METHODS: In this study, the effects of citrate anticoagulation on
      leukocyte and granulocyte counts, complement activation, and the expression of
      CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during
      hemodialysis with unmodified cellulose membranes. Standard heparin was compared
      to citrate in three different schedules: citrate was infused to obtain a
      concentration of either 7 or 10 mmol/l blood. CaCl(2) was administered into the
      dialyzer outlet at 8. 25 mmol Ca(2+)/h (citrate 10 mmol/l) or at 11 mmol Ca(2+)/h
      (citrate 7 and 10 mmol/l) to reconstitute the calcium levels in the blood
      returning to the patient. RESULTS: The use of citrate at a high concentration (10
      mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet
      and at the outlet bloodline; for CD11c a reduced upregulation was observed on
      granulocytes harvested from the inlet bloodline. No effects of citrate were
      observed on leukopenia, granulocytopenia, or complement activation. A positive
      correlation between the decrease in systemic ionized Ca(2+) concentration and the
      increase in CD11b and CD11c expression was found. CONCLUSION: Citrate/CaCl(2)
      administration affects leukocyte adhesion molecule expression in a dose-dependent
      way; however, no significant effect could be demonstrated on leukopenia and
      complement activation.

PMID- 10940745
TI  - Increased maintenance corticosteroids during upper respiratory infection decrease
      the risk of relapse in nephrotic syndrome.
AB  - Relapses are common in children with idiopathic nephrotic syndrome, and this
      prospective study looks into the possibility of decreasing the frequency of
      relapses in a selected group of such patients. The study includes 36 children
      with a steroid-dependent, relapsing nephrotic syndrome on a maintenance
      prednisone therapy of about 0.5 mg/kg every other day. They were prospectively
      divided into two groups with comparable age and sex distribution and the number
      of those who had previously received cyclophosphamide therapy. Group 1 patients
      were advised to take daily prednisone for 5 days, starting at the time of the
      onset of an upper respiratory tract infection (URI). No such advice was given to
      those in group 2, and they remained on alternate-day prednisone during URI. At
      the end of a 2-year follow-up period, the total number of relapses in group 1 was
      40 with a mean of 2.2 +/- 0.87 per patient as compared with 99 with a mean of 5.5
      +/- 1.33 per patient in group 2 (p = 0.04). We conclude that an increased
      maintenance prednisone during URI helps decrease significantly the number of
      relapses in those on alternate-day therapy.

PMID- 10940746
TI  - Prosthetic graft placement using the deep forearm veins in hemodialysis patients:
      a preliminary report.
AB  - When the superficial arm veins are not suitable for the creation of a
      conventional endogenous arteriovenous (A-V) fistula or the placement of a
      prosthetic graft in the forearm, the use of the deep forearm veins as an outflow
      system to construct an A-V graft access seems to be a reasonable alternative.
      Using this approach, we placed 6 prosthetic grafts in 6 hemodialysis patients in
      whom conventional methods had failed. Adequate functioning of this 'deep vein'
      type vascular access in these 6 patients has been maintained for 3, 6, 11, 15, 19
      and 24 months, respectively, without complications or any need for further
      interventions. Only one graft failed after 6 months. Our preliminary results
      indicate that this technique can be used successfully when the superficial
      forearm veins have been exhausted, thus avoiding the use of upper-arm or axillary
      veins.

PMID- 10940747
TI  - Use of 'locked-in' antibiotic to treat an unusual gram-negative hemodialysis
      catheter infection.
AB  - A 37-year-old woman on maintenance hemodialysis for 3 years had multiple vascular
      access failures due to antiphospholipid syndrome. She was dialyzed via a tunneled
      left subclavian catheter, but after 1 year developed chills and fever during each
      dialysis session. Blood cultures grew out Xanthomonas maltophilia sensitive to
      ceftazidime and ciprofloxacin. Intravenous administration of both antibiotics
      failed to eradicate infection. We added 'locked-in' ceftazidime, instilling it
      daily into the catheter along with heparinized saline for 3 weeks. Within 24 h
      the patient was dialyzed uneventfully, and all subsequent blood cultures have
      been negative. This case shows the successful use of a 'locked-in' antibiotic to
      treat an unusual gram-negative catheter infection. Two prior series have reported
      similar good results in infections with more common organisms. Such treatment may
      permit continued use of tunneled hemodialysis catheters for longer periods.

PMID- 10940748
TI  - Successful interventional treatment of renal insufficiency caused by renal artery
      pseudoaneurysm with concomitant arteriovenous fistula.
AB  - Asymptomatic arteriovenous fistulae and pseudoaneurysms are common after renal
      biopsy. We present a patient with a single kidney and symptomatic pseudoaneurysm
      of the renal artery with concomitant arteriovenous fistula as a rare complication
      following surgical embolectomy. The patient developed renal insufficiency because
      of a significant degree of vascular steal caused by the fistula. Dialysis was
      performed for more than 6 months until the fistula was diagnosed. The fistula and
      the pseudoaneurysm were successfully treated by superselective arterial
      embolization with metallic coils. Renal function improved within the next 2 weeks
      and no further dialysis was necessary.

PMID- 10940749
TI  - Amlodipine besylate induced acute interstitial nephritis.
AB  - Adverse effects of amlodipine besylate, a widely used antihypertensive
      medication, include peripheral edema, flushing, headache, pruritus, and rash. An
      adverse renal effect attributable to the medication has hitherto not been
      reported in the literature. We herein report a case of amlodipine besylate
      induced acute interstitial nephritis.

PMID- 10940750
TI  - HBV and HCV infections in relation to the chosen genetic features in hemodialyzed
      patients.

PMID- 10940751
TI  - Increasing erythropoietin dose overcomes inadequate erythropoietin response
      secondary to cardiac hemolysis.

PMID- 10940752
TI  - Increased plasma levels of adrenomedullin in patients with hemodialysis.

PMID- 10940753
TI  - Prevalence of anti-HCV positivity in hemodialysis patients.

PMID- 10940754
TI  - Hemoperfusion with polymyxin B-immobilized fiber reduces urinary podocyte numbers
      in patients with severe sepsis.

PMID- 10940755
TI  - Bronchial stenosis and extensive bronchiectasis due to Wegener's granulomatosis.

PMID- 10940756
TI  - Anti-neutrophil cytoplasmic antibody-positive crescentic nephritis occurring
      together with renal cell carcinoma.

PMID- 10940757
TI  - Polymorphonuclear cytosolic Ca(2+) concentration before and after activation in
      chronic renal failure.

PMID- 10940758
TI  - Hippocampal perfusion and pituitary-adrenal axis in Alzheimer's disease.
AB  - The hippocampus is involved in Alzheimer's disease (AD) and regulates the
      hypothalamus-pituitary-adrenal axis (HPAA). Enhanced cortisol secretion has been
      reported in AD. Increased cortisol levels affect hippocampal neuron survival and
      potentiate beta-amyloid toxicity. Conversely, dehydroepiandrosterone (DHEA) and
      its sulfate (DHEAS) are believed to antagonize noxious glucocorticoid effects and
      exert a neuroprotective activity. The present study was aimed at investigating
      possible correlations between hippocampus perfusion - evaluated by SPECT - and
      HPAA function in AD. Fourteen patients with AD and 12 healthy age-matched
      controls were studied by (99m)Tc-HMPAO high-resolution brain SPECT. Plasma
      adrenocorticotropin, cortisol, and DHEAS levels were determined at 2.00, 8.00,
      14.00, 20.00 h in all subjects and their mean values were computed.
      Cortisol/DHEAS ratios (C/Dr) were also calculated. Bilateral impairment of SPECT
      hippocampal perfusion was observed in AD patients as compared to controls. Mean
      cortisol levels were significantly increased and DHEAS titers were lowered in
      patients with AD, as compared with controls. C/Dr was also significantly higher
      in patients. Using a stepwise procedure for dependent SPECT variables, the
      variance of hippocampal perfusional data was accounted for by mean basal DHEAS
      levels. Moreover, hippocampal SPECT data correlated directly with mean DHEAS
      levels, and inversely with C/Dr. These data show a relationship between
      hippocampal perfusion and HPAA function in AD. Decreased DHEAS, rather than
      enhanced cortisol levels, appears to be correlated with changes of hippocampal
      perfusion in dementia.

PMID- 10940760
TI  - No evidence for association of alpha 1a adrenoceptor gene polymorphism and
      clozapine-induced urinary incontinence.
AB  - Clozapine is an effective atypical antipsychotic that has high affinity for many
      neurotransmitter receptors. Among the adverse effects of clozapine, urinary
      incontinence is commonly found and is suggested to be caused by alpha-adrenergic
      blockade. We tested the hypothesis that clozapine-induced urinary incontinence is
      related to a genetic variant of the alpha(1a)-adrenoceptor. We also tested
      whether the alpha(1a)-receptor gene confers susceptibility to schizophrenic
      disorders. Our result indicated that the alpha(1a)-adrenoceptor gene polymorphism
      investigated plays no major role in the pathogenesis of schizophrenia or in
      clozapine-induced urinary incontinence. Considering the superior effects of
      clozapine and its potent adrenergic antagonistic effects, it is of interest to
      investigate the association between this polymorphism and the treatment response.

PMID- 10940759
TI  - Aggressive behavioral characteristics and endogenous hormones in women with
      Bulimia nervosa.
AB  - Increased aggressiveness frequently occurs in patients with bulimia nervosa (BN),
      but its neurobiological correlates have been poorly investigated. In this study,
      we investigated possible relationships between such clinical measure and blood
      levels of endogenous hormones in patients with BN. Morning plasma levels of
      testosterone, 17beta-estradiol, prolactin (PRL) and cortisol were measured in 33
      bulimic women and 22 healthy female controls. The eating-related psychopathology,
      depression and aggressiveness were rated by specific psychometric scales. Bulimic
      patients showed decreased plasma levels of PRL and 17beta-estradiol, and
      increased concentrations of cortisol and testosterone. Moreover, patients scored
      higher than healthy controls on rating scales assessing eating-related
      psychopathology, depressive symptoms and aggressiveness. A significant positive
      correlation was found between testosterone plasma levels and aggressiveness in
      patients but not in controls. These findings suggest that in BN, increased plasma
      levels of testosterone may play a role in the modulation of aggressiveness.

PMID- 10940762
TI  - Effects of selective serotonin reuptake inhibitors on objective and subjective
      sleep quality.
AB  - The purpose of this paper is to review the effects of selective serotonin (5-HT)
      reuptake inhibitors on objective and subjective sleep and awakening quality
      measures. Polysomnography (PSG) demonstrated in both healthy volunteers and
      depressed patients a decrease in sleep efficiency and total sleep time, a
      lengthening of sleep latency and a deterioration in sleep continuity, including
      an increase in the number of awakenings and wake time during the total sleep
      period. Sleep architecture mostly showed an increase in S1 and S2 and a decrease
      in S3, S4 and REM sleep as well as a lengthening of REM latency. Objective
      awakening quality, if measured at all by psychometry, generally showed no
      decrements. Concerning subjective sleep and awakening quality, normals
      demonstrated either no changes or a tendency towards a deterioration, while in
      patients some improvement was observed. Reasons for this discrepancy will be
      discussed. Novel 5-HT reuptake inhibitors with additional modes of action such as
      5-HT2 antagonism (e.g. trazodone, nefazodone) are more likely to improve
      objective and subjective sleep quality, although some shortcomings may be
      inherent in regard to comorbidity (e.g. sleep-related breathing disorders). Thus,
      PSG seems to be a necessity for diagnosis and treatment of complex sleep
      disorders.

PMID- 10940761
TI  - Apolipoprotein E epsilon3 allele is not a risk factor of schizophrenia: a study
      of 314 Japanese patients.
AB  - The association between apolipoprotein E (ApoE) alleles and schizophrenia has
      remained controversial. A recent report claiming that ApoE epsilon3 Taiwan
      Chinese carriers have an increased risk of schizophrenia prompted us to
      investigate the allele frequency in a large group of Japanese schizophrenic
      patients. Serum samples were obtained from 314 schizophrenic patients and 188
      controls in Japan and examined using isoelectric focusing/immunoblotting. There
      were no significant differences in ApoE allele frequencies between schizophrenic
      patients and controls and in the odds ratios for schizophrenia among the
      epsilon2, epsilon3 and epsilon4 carriers. In contrast to the report from Taiwan,
      our findings and results of the majority of previous studies suggest no effects
      of ApoE alleles on the development of schizophrenia.

PMID- 10940763
TI  - Neuroendocrine responses to psychological stress in adolescents with anxiety
      disorder.
AB  - Neurotransmitter-neuroendocrine and cardiovascular responses to the
      administration of a psychologically stressful mixed-model test (Mental
      Arithmetic, Stroop Color Word Interference Task, Trier Social Stress Test) were
      examined in 20 male peripubertal subjects affected by anxiety disorder (group A:
      14 with generalized anxiety disorder, 6 with generalized anxiety disorder and
      separation anxiety disorder) and 20 junior school adolescents, matched for age,
      without overt psychological disorders (group B). Plasma levels of norepinephrine
      (NE), epinephrine (EPI), adrenocorticotropic hormone (ACTH), beta-endorphin (beta
      EP), cortisol (CORT), growth hormone (GH), prolactin (PRL) and testosterone (Te)
      were measured immediately before the beginning of the tests and 30 min later at
      their end. Mean prestress values of GH, PRL, beta-EP and ACTH were significantly
      higher in anxious subjects than in controls. There was no difference in NE, EPI,
      CORT and Te prestress levels in the two groups. After the psychological stress
      session NE, GH and Te concentrations increased significantly in anxious subjects
      (A), but not in controls. In contrast, beta-EP and PRL decreased significantly
      during the psychological stress session in anxious subjects, and were unaffected
      by stress in the subjects without anxiety. No significant changes were found in
      ACTH, CORT and EPI during the challenge either in anxious subjects or in
      controls, which may be attributed to the late time of poststress blood sampling.
      In contrast to controls, heart rate and systolic blood pressure increased
      significantly in anxious subjects after psychological stress testing. Our data
      support the hypothesis that the hyperactivity of the noradrenergic system in
      response to stress is associated with anxiety disorders in adolescents and might
      influence the responses of GH and Te. High prestress basal values of stress
      hormones seem to be induced in anxious subjects by the anticipation of the task
      or by a persistent hyperactivity of the noradrenergic system. Further studies are
      needed to investigate in more detail the involvement of the HPA axis in anxious
      adolescents by a more refined resolution of time points of blood sampling.

PMID- 10940764
TI  - Gender differences in the EEG of abstinent cocaine abusers.
AB  - Gender differences in the EEG were explored in cocaine-abusing individuals not
      seeking treatment. Twenty currently abstinent cocaine-abusing females aged 21-41
      were studied. Their cocaine use history was matched to 20 currently abstinent
      cocaine-abusing males. Twelve female and 20 male non-drug-abusing individuals
      served as a control group. Resting eyes closed EEG was recorded from 8 leads. The
      males who used cocaine had elevated EEG beta (p<0.0125) and reduced alpha
      (p<0.0125) when compared to the cocaine-abusing females and control subjects.
      These findings suggest that the EEG of cocaine-abusing women may be more normal
      than that of cocaine-abusing men. Such gender-specific differences for cocaine
      abusing populations may require gender-specific treatment to improve outcome.

PMID- 10940765
TI  - Alterations of continuous MEG measures during mental activities.
AB  - In a pilot study, we investigated the topography of 11 continuous MEG measures
      for the eyes-opened and eyes-closed condition together with three simple mental
      tasks (mental arithmetic, visual imagery, word generation). One-minute recordings
      for each condition from 16 right-handed subjects were analyzed. The
      electrophysiological measures consisted of 6 spectral band measures together with
      spectral edge frequency and spectral entropy, plus the time-domain-based entropy
      of amplitudes (ENA) and the nonlinear measures correlation dimension D2 and
      Lyapunov exponent L1. In summary, our results indicate a pronounced task
      dependent difference between the anterior and the posterior region, but no
      lateralization effects. Although the nonlinear measures ranged in the middle
      field with respect to the number of significant contrasts, they were the only
      ones to be partially successful in discriminating the mental tasks from each
      other. The most efficient measure turned out to be the ENA. Under mental
      activation the ENA was larger than in both no task conditions (eyes opened and
      eyes closed). This finding reflects lower variations of the maximum amplitude
      during performance of mental tasks than during no task states.

PMID- 10940766
TI  - Trampoline injuries of the cervical spine.
AB  - Trampolines were responsible for over 6,500 pediatric cervical spine injuries in
      1998. This represents a five-fold increase in just 10 years. While most have been
      minor, paraplegia, quadriplegia and death are all reported. We present 2 cases of
      trampoline-related cervical spine injury and review the relevant literature.
      Additionally, we examine the efforts made to reduce the incidence of trampoline
      injuries, and discuss why these have failed. We conclude that safety guidelines
      and warnings are inadequate. In addition, we support recommendations for a ban on
      the use of trampolines by children.

PMID- 10940767
TI  - Traumatic acute giant epidural hematoma in a hydrocephalic shunted child.
AB  - Extradural hematoma (EDH) is considered to be a rare complication of head trauma
      in children, and represents a serious and urgent pathology from which complete
      recovery can be expected if specialized treatment is instituted in time. In this
      article, the authors report the potential danger to a hydrocephalic shunted child
      who was apparently asymptomatic at the time of hospital admission with a mild
      head injury and developed an EDH of venous origin. This child had a rapid (time
      interval from injury to decerebrate posture of about 2 h), atypical (remained
      asymptomatic most of the time until abruptly deterioration) and fatal course,
      stressing the importance of early diagnosis and rapid therapy in order to avoid
      the death of the patient. The authors discuss the role of the
      ventriculoperitoneal shunting system in the lack of clinical symptoms associated
      with the presence of a giant EDH and a rapid and fatal course, and stress the
      importance of computed tomographic (CT) scanning in these patients, even if they
      are asymptomatic. If a skull fracture is suspected, a CT scan must be performed
      without delay.

PMID- 10940768
TI  - Evaluation of shunt malfunction using shunt site reservoir.
AB  - OBJECTIVE: To determine the usefulness of a separate reservoir placed at the site
      of the shunt in evaluation of shunt malfunction. METHODS AND MATERIALS: A
      ventricular catheter was placed alongside the proximal catheter of the shunt and
      connected to a subgaleal reservoir in 17 patients, in 9 a double-lumen catheter
      with integrated reservoir and in 13 patients a dual catheter with a double-port
      reservoir was used. At presentation of suspected shunt malfunction, a standard
      shunt function evaluation using shunt tap, CT scan or shunt injection was
      performed, and subsequently, the pressure from the tap of the reservoir was
      obtained. RESULTS: Thirty-three patients presented with symptoms of malfunction
      at an interval of 2.3 +/- 3 months (range 2-429 days). The pretest probability of
      shunt malfunction in this population was 73%. Posttest probability of shunt
      malfunction was 82.5% with standard evaluation and improved to 100% by the
      separate reservoir tap pressure measurement. In 4 patients in whom the shunt tap
      was dry, shunt infection was diagnosed prior to revision using CSF obtained at
      the reservoir tap. In 5 patients with proximal malfunction and bradycardia, the
      reservoir tap allowed early ventricular decompression. CONCLUSION: This study
      shows that a reservoir placed at the site of the shunt remains patient even when
      the shunt malfunctions, suggesting that flow rather than catheter position is
      important in proximal malfunction. It is superior to shunt tap for detection of
      shunt malfunction and infection, and it allows early ventricular decompression in
      a sick patient awaiting surgery for shunt revision.

PMID- 10940769
TI  - Multiple genomic alterations including N-myc amplification in a primary large
      cell medulloblastoma.
AB  - The large cell (LC) subtype is a recently described histologic variant of
      medulloblastoma (Mb) associated with a rapid and aggressive clinical course. We
      describe the genomic profile of a LC-Mb tumor obtained from a patient who
      developed recurrent and fulminant disease despite 'good-risk' features at
      diagnosis and state- of-the-art multidisciplinary therapy. The tumor sample was
      analyzed using comparative genomic hybridization (CGH) and complementary
      molecular approaches. CGH revealed amplicons at chromosome bands 2p24-25, 2q12
      22, and 17p11; losses of chromosomes 11q and 18; and low-level gains of 3q, 11p,
      13q and 14q. Southern blot analysis confirmed N-myc amplification. No evidence of
      p53 mutation was detected. The genomic profile of this LC-Mb tumor sample
      revealed a distinctive pattern of genetic alterations including amplification of
      N-myc and anonymous oncogenes at chromosome bands 2q12-22 and 17p11. These
      genomic abnormalities are uncommon in other subtypes of Mb.

PMID- 10940770
TI  - Management of choroid plexus tumours in children: 20 years experience at a single
      neurosurgical centre.
AB  - OBJECTIVE: Tumours of the choroid plexus are rare tumours of neuro-ectodermal
      origin, accounting for less than 1% of all intracranial tumours. Most cases
      present in children less than 2 years of age. While choroid plexus carcinomas
      (CPC) are reported to have an extremely poor prognosis, choroid plexus papillomas
      (CPP) are generally regarded as benign tumours with a very favourable long-term
      outcome. Management dilemmas are associated with the choice of surgical
      procedure, tumour vascularity, the treatment of hydrocephalus and the value of
      adjuvant therapy. The objective of this study was to review our experience with
      this rare tumour over a 20-year period. METHODS: Patients were identified from
      the Great Ormond Street Neurosurgical Brain Tumour Database. Over a 20-year
      period (1979-1999), 34 children were identified with a choroid plexus tumour.
      There were 25 cases of CPP and 9 cases of CPC. A retrospective review of case
      notes, radiological imaging, operation reports and pathology was performed.
      RESULTS: The median age at presentation was 17 months (1-138) for CPP and 13
      months (2-102) for CPC. There was no sex difference for CPP. However, 8 of the 9
      CPCs were male (89%). A complete surgical resection was achieved in all 25 cases
      of CPP and in 3 cases of CPC (33%). The median survival for CPPs was 75.5 months
      (2-228), with a median follow-up of 73.5 months (2-228). The median survival for
      CPCs was 6 months (1-90), with a median follow-up of 6 months (1-90). CONCLUSION:
      With modern neurosurgical practise, a cure should be the aim for all children
      with CPP. There is no evidence that adjuvant therapy has any role in the primary
      management of these children. However, CPC still has an extremely poor prognosis,
      and the efficacy of adjuvant therapy remains to be established.

PMID- 10940771
TI  - Successful treatment of a neonate with vein of Galen aneurysmal malformation.
AB  - We present a follow-up study on a 5-year-old boy who was born with vein of Galen
      aneurysmal malformation (VGAM) accompanied by extreme cardiovascular distress. He
      was successfully treated by the staged endovascular technique during the neonatal
      stage. Postoperative angiographic study confirmed complete occlusion of the VGAM
      and the establishment of normal brain perfusion. At 5 years of age, the child is
      growing normally without neurological deficits or developmental retardation. We
      suggest that the restoration of normal brain perfusion in neonates with VGAM can
      cause normal brain development.

PMID- 10940772
TI  - Fibrous dysplasia of the orbit in an infant.
AB  - Fibrous dysplasia is an idiopathic fibro-osseous lesion of the skeletal bones.
      These uncommon osseous lesions usually manifest within the first two decades of
      life. Its occurrence during infancy is extremely uncommon, and we describe here a
      case of fibrous dysplasia involving the orbit in a 9-month-old male child.

PMID- 10940773
TI  - Fibromyxoma of the petrous apex.
AB  - The common petroclival bony tumors are chordoma and chondrosarcoma. Myxoma of the
      bone occurs only in the facial bones, and it has not been reported in skull
      bones. The computed tomographic scanning, magnetic resonance imaging and
      intraoperative characteristics of a case of fibromyxoma of the petrous bone in a
      14-year-old girl are described.

PMID- 10940774
TI  - Pathology of diencephalic astrocytomas.
AB  - Pediatric gliomas span a spectrum of neoplasms ranging from the well
      circumscribed, slowly growing lesions that can be totally removed by surgery to
      highly infiltrating, nonexcisable, rapidly growing tumors that resist any form of
      postoperative therapy. As part of this symposium, we discuss selected members of
      this group in the diencephalon, where lesions of both extremes are common in
      children. The report illustrates and contrasts the clinical, radiographic and
      pathological features of the two classic regional astrocytomas, pilocytic and
      fibrillary, as well as two less common but distinctive lesions, pilomyxoid
      astrocytoma and bithalamic astrocytoma.

PMID- 10940775
TI  - Meningioangiomatosis.

PMID- 10940776
TI  - Concerning the article by Winston and Wang, Pediatr Neurosurg 1999;31:225-230.
      Cranial bone fixation in infants and children.

PMID- 10940777
TI  - Inhibition of T-type and L-type Ca(2+) currents by aranidipine, a novel
      dihydropyridine Ca(2+) antagonist.
AB  - The effects of aranidipine, a novel dihydropyridine Ca(2+) channel antagonist, on
      membrane currents in guinea pig ventricular myocytes and on action potentials in
      rabbit sinoatrial node tissue were examined. In myocytes, aranidipine (10 nmol/l
      to 1 micromol/l) concentration-dependently decreased T-type and L-type Ca(2+)
      currents. Aranidipine (1 micromol/l) had little effect on K(+) currents. In the
      sinoatrial node, 0.1 micromol/l aranidipine increased cycle length, and decreased
      +V(max) and the slope of the phase 4 depolarization. Thus, inhibition of both T
      type and L-type Ca(2+) currents by aranidipine may partly explain its potent
      negative chronotropic activity.

PMID- 10940778
TI  - Site-directed mutagenesis implicates a threonine residue in TM6 in the subtype
      selectivities of UH-AH 37 and pirenzepine at muscarinic receptors.
AB  - The structural basis for the selectivity of the antagonist UH-AH 37 at human
      muscarinic acetylcholine receptors was investigated by expressing mutant
      receptors in COS-7 cells. Previous studies have demonstrated that the interaction
      between UH-AH 37 and [(3)H]N-methylscopolamine in equilibrium assays is
      competitive and that the high affinity of UH-AH 37 for the M(5) subtype, compared
      to M(2), is due to an epitope in the sixth transmembrane domain (TM6) or the
      third outer loop of the receptor. By mutating each nonconserved residue in this
      region of M(2) and M(5) to its counterpart in the other receptor, we identified a
      threonine residue in the middle of TM6 uniquely responsible for the higher
      affinity of the M(5) receptor (M(1), M(3), and M(4) receptors also carry a
      threonine at that location and also have high affinity for UH-AH 37). The mutant
      receptor in which the corresponding alanine of the M(2) receptor was replaced by
      threonine, M(2)(401)ala --> thr, expressed enhanced affinity for pirenzepine as
      well as for UH-AH 37. The chick M(2) receptor, which expresses anomalously high
      affinity for pirenzepine, differs from its mammalian counterparts by the presence
      of a threonine at this position. Affinities of AF-DX 116 and 4-DAMP, as well as
      the allosteric potency of UH-AH 37, were not sensitive to the M(2)(401) ala -->
      thr mutation.

PMID- 10940779
TI  - Effect of a novel anti-allergic agent, HSR-609, on antigen-induced airway
      hyperresponsiveness in mice.
AB  - The effects of a newly synthesized anti-allergic agent, HSR-609, on allergic
      airway hyperresponsiveness and airway inflammation have been studied in
      sensitized mice. The effects were compared with those of two histamine H(1)
      receptor antagonists, cetirizine and terfenadine, and prednisolone. Three
      inhalations of antigen caused an increase in leukocytes (including eosinophils)
      with increases in IL-5 in BALF and airway hyperresponsiveness to acetylcholine in
      BALB/c mice. All drugs were orally administered once a day for 10 days from the
      day before the first inhalation of antigen. HSR-609 (10 mg/kg) and prednisolone
      (5 mg/kg) significantly inhibited the antigen-induced airway hyperresponsiveness,
      whereas cetirizine (10 mg/kg) or terfenadine (100 mg/kg) did not affect this
      airway response. At the same time HSR-609 inhibited the antigen-induced
      eosinophilia and IL-5 production in BALF. Prednisolone also showed an inhibitory
      effect on the airway eosinophilia and IL-5 production but not cetirizine and
      terfenadine in the same experiments. In addition, HSR-609 (p.o.) dose-dependently
      suppressed the accumulation of eosinophils elicited by antigen-stimulated D10G4.1
      cells, a murine Th2 clone, in peritoneal cavity lavage fluid in AKR/J mice. These
      results suggest that HSR-609 inhibits allergic airway hyperresponsiveness to
      acetylcholine probably because of the inhibition of Th2-dependent eosinophilia
      caused by IL-5. In addition, effects of HSR-609 were different from those of
      cetirizine and terfenadine concerning the inhibition of antigen-induced airway
      hyperresponsiveness in mice.

PMID- 10940780
TI  - Bimodal expression of CYP2D16 in the guinea pig adrenal cortex.
AB  - Prior studies revealed an apparent bimodal distribution of adrenal xenobiotic
      metabolizing activities in outbred guinea pigs. High activities were
      characteristic of most animals but a minority had very low rates of metabolism.
      The present studies were done to determine the basis for this distribution. Among
      the enzymatic activities abundant in guinea pig adrenal microsomes is bufuralol
      1'-hydroxylation, a marker for CYP2D isozymes. Western blot analyses revealed
      that adrenal expression of CYP2D16, the guinea pig CYP2D analogue, was highly
      correlated with xenobiotic-metabolizing activities. Of 12 animals studied, 4 had
      low levels of adrenal CYP2D16 expression and correspondingly low bufuralol 1'
      hydroxylase and benzphetamine N-demethylase activities. In contrast, adrenal
      expression of steroidogenic P450 isozymes (CYP17 and CYP21) and the corresponding
      steroid hydroxylase activities were similar in all animals. There was also no
      evidence of polymorphism in hepatic xenobiotic metabolism. The results suggest
      that the bimodal expression of adrenal CYP2D16 is at least partly responsible for
      the variability in adrenal xenobiotic metabolism, and that this pattern of
      expression is not applicable to other adrenal P450 isozymes or to hepatic
      CYP2D16. Further studies are needed to determine if genetic polymorphism is
      responsible for the mode of adrenal CYP2D16 expression.

PMID- 10940781
TI  - Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the
      recurrence of gastric ulcer after healing by drug treatment in rats.
AB  - We investigated the recurrence of ulcers in rats after treatment with FRG-8813,
      (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2
      butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric
      ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing
      and recurrence after treatment with FRG-8813 or famotidine were evaluated by
      endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment
      with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer
      had healed, accelerated the ulcer healing significantly. A subsequent follow-up
      study on the healed rats showed that the cumulative recurrence rate of rats
      healed by FRG-8813 was lower than that of naturally healed rats or rats healed by
      famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was
      normal in contrast with the control of famotidine-healed animals. The mucosal
      regeneration index of the gastric ulcer after 10 days' administration of FRG-8813
      was significantly higher than that obtained with famotidine. After cessation of
      the treatment with famotidine for 7 days, rebound hyperacidity was induced; but
      such rebound did not occur with FRG-8813. Considering the low recurrence rate of
      ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide
      additional benefits in peptic ulcer therapy.

PMID- 10940782
TI  - Effect of mometasone furoate by topical application on allergic rhinitis model in
      rats.
AB  - The effects of mometasone furoate on experimental allergic rhinitis in rats were
      studied in comparison with that of fluticasone propionate. Topical application of
      both drugs inhibited dose-dependently the increase of nasal symptoms (sneezing
      and nasal rubbing) after antigen challenge to the nasal cavity of actively
      sensitized rats. Mometasone furoate and fluticasone propionate at concentrations
      of 0.01 or 0.1% significantly inhibited both nasal rubbing and sneezing 1 h after
      topical application of both drugs. The relative potencies of mometasone furoate
      in nasal rubbing and sneezing compared to fluticasone propionate were 5.01 and
      6.87, respectively. Mometasone furoate (0.02%) and fluticasone propionate (0.1%)
      significantly inhibited the increase of antigen-induced nasal rubbing even 6 h
      after topical application, indicating that both drugs have a long-lasting effect.

PMID- 10940783
TI  - Differential involvement of opioid receptors in stress-induced antinociception
      caused by repeated exposure to forced walking stress in mice.
AB  - We examined the effects of repeated exposure to forced walking stress for 6 h
      once a day for 0, 6 and 9 consecutive days on formalin-induced paw licking in
      mice. In each observation period, stress-induced antinociception (SIA) was
      observed only in the late phase (from 10 to 30 min), but not in the early phase
      (from 0 to 10 min) of formalin-induced paw licking in mice. Moreover, it was hard
      to develop tolerance even by daily exposure to stress for 6 days, although SIA
      for 9 days decreased compared with those for 0 and 6 days. Naloxone (10 mg/kg),
      an opioid-receptor antagonist, was effective in reducing the SIA induced by
      forced walking stress for 6 days and/or 9 days, but not for 0 days. Furthermore,
      the experiments with selective opioid-receptor antagonists, beta-funaltrexamine
      (mu) naltrindol (delta), or nor-binaltorphimine (kappa) demonstrated that SIA
      induced by forced walking stress for 9 successive days may be mediated through
      opioid delta- and kappa-receptors. Finally, although SIA seemed to be a unitary
      phenomenon, the present results strengthened the idea that SIA is induced by
      exposure to forced walking stress with characteristics dependent on the duration
      of exposure.

PMID- 10940784
TI  - Vasodilatory effect of adrenomedullin in mouse aorta.
AB  - Human adrenomedullin (AM) and human calcitonin gene-related peptide (CGRP)
      produced a concentration-dependent relaxation in mouse aorta, precontracted with
      noradrenaline. EC(50) values for AM and CGRP were 9.8 +/- 2.4 and 4.2 +/- 0.1
      nmol/l, respectively. AM-mediated vasorelaxation was partially (3-fold) shifted
      by AM(22-52), the C-terminal AM fragment, but not by CGRP(8-37), a selective
      CGRP1 antagonist. Both AM(22-52) and CGRP(8-37) failed to inhibit CGRP-mediated
      vasorelaxation of mouse aorta rings. Binding of rat [(125)I]AM to these membranes
      was specific. Both human AM and AM(22-52) displaced rat [(125)I]AM binding in a
      concentration-dependent manner with IC(50) values of 12.0 +/- 4 and 19.4 +/- 8
      nmol/l, respectively. In contrast, both human CGRP and CGRP(8-37) were weak in
      displacing [(125)I]AM binding. Very little specific binding was observed with
      [(125)I]CGRP. In conclusion, the data presented here demonstrate that the mouse
      aorta displays AM receptors that mediate vasorelaxation.

PMID- 10940785
TI  - Role of nitric oxide in gastric injury induced by hemorrhagic shock in rats.
AB  - The aim of this study was to investigate the effect of nitric oxide (NO) on the
      gastric injury induced by hemorrhagic shock. Hemorrhagic shock was created by
      withdrawing 3 ml blood/200 g body weight of the rats. Before the hemorrhage, N(G)
      nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.v. bolus), D-NAME (10 mg/kg
      i.v. bolus), or L-arginine (100 mg/kg i.v. bolus and 10 mg/kg/min infusion) + L
      NAME were administered. At the end of the 1-hour hypovolemic shock period,
      histological analysis, gastric ulcer index, gastric myeloperoxidase (MPO)
      activity, and gastric protein oxidation (PO) levels were determined. In
      histological analysis a destructive effect of L-NAME (NO synthase inhibitor) was
      demonstrated. L-NAME treatment increased gastric MPO activity, L-arginine
      reversed this effect and D-NAME had no effect. Tissue PO activity was found to be
      increased in L-NAME-treated rats; L-arginine treatment reversed this activity. It
      is concluded that gastric barrier function is altered after hemorrhagic shock,
      and L-arginine (NO precursor) can prevent mucosal injury in the stomach. This
      effect of NO may be on gastric blood flow and can be mediated by tissue
      neutrophils.

PMID- 10940786
TI  - Future pharmacological treatment of cystic fibrosis.
AB  - Cystic fibrosis (CF) is an autosomal recessive disorder that is caused by over
      850 different mutations in the CF gene. It is useful to group these mutations
      according to the defect that results in the CFTR mRNA or protein. New
      pharmacological treatments targeted towards specific mutations that are
      relatively common are being developed. Class I mutations do not produce CFTR
      protein because of a premature stop signal in the CFTR DNA. These null mutations
      can be corrected by certain aminoglycosides which cause the aberrant stop signal
      to be skipped. Mutations leading to a CFTR protein that attains an unstable
      structure shortly after translation in the endoplasmic reticulum form class II.
      Class II mutations can be restored to the protein trafficking pathway by
      manipulation of chaperone protein/CFTR interactions with chemical chaperones or
      drugs that affect gene regulation such as the butyrates. Production of a CFTR
      with reduced Cl(-) transport on the basis of abnormal regulation of the chloride
      channel is the basis of class III. Genistein can overcome this block in
      regulation. Mutations that partially reduce chloride conductance through CFTR
      (class IV) can be stimulated with milrinone, which is a phosphodiesterase
      inhibitor. Finally, mutations that lead to a severe reduction in normal CFTR
      protein form class V. Increased levels of CFTR could be generated with the
      butyrates or supplemented with gene therapy. Although most of the reported
      mutations in CFTR are rare and unclassified, it may be possible to use genotype
      phenotype correlations to determine the best approach.

PMID- 10940787
TI  - Feedback-controlled negative pressure ventilation in patients with stable severe
      hypercapnic chronic obstructive pulmonary disease.
AB  - BACKGROUND: In recent studies, the efficacy of intermittent rest of the
      inspiratory muscles as an option of treating patients with severe chronic
      obstructive pulmonary disease (COPD) has become questionable. OBJECTIVE: The aim
      of our study was to analyze the effects of feedback-controlled intermittent
      negative pressure ventilation (INPV) on stable, but severely hypercapnic COPD
      patients. METHODS: 21 clinically stable, hypercapnic patients with severe COPD
      underwent INPV with chest shells for 3 weeks, 6 h a day. The INPV sessions were
      optimized by a visual biofeedback system, which enabled control over the decrease
      in diaphragmatic activity. Respiratory muscle (RM) function parameters, lung
      function parameters, blood gases and exercise capacity were analyzed. RESULTS: In
      the end, 19 patients concluded INPV treatment. They had PaO(2) of 56.5 +/- 11.8
      mm Hg, PaCO(2) of 50.2+/-2.7 mm Hg (mean +/- SD) and FEV(1) of 27.8 +/- 4.3%
      predicted before treatment. There was no statistically significant change in lung
      function parameters, RM function parameters, physical performance and level of
      dyspnea after 3 weeks of INPV. CONCLUSION: We conclude that intermittent RM rest
      induced by INPV can relax inspiratory muscles in most patients with stable severe
      COPD, but fails to improve RM function and exercise capacity.

PMID- 10940788
TI  - Left ventricular function in patients with obstructive sleep apnoea syndrome
      before and after treatment with nasal continuous positive airway pressure.
AB  - BACKGROUND: Previous studies have yielded disparate results regarding the effect
      of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function.
      OBJECTIVES: In order to clarify this, we performed a prospective study
      investigating OSA patients with no history of systemic hypertension, coronary
      artery disease, myocardial, pericardial or valvular problems, asthma or chronic
      obstructive pulmonary disease before and after treatment with nasal continuous
      positive airway pressure (nCPAP). METHODS: Fifteen patients (3 women, 12 men)
      with an apnoea/hypopnoea index >15 (mean +/- SD = 52 +/- 21) were studied with
      complete polysomnography, ambulatory blood pressure monitoring, M-mode two
      dimensional echocardiography and pulsed Doppler echocardiography in two phases,
      i.e. before and after 12-14 weeks of nCPAP therapy. We measured systolic and
      diastolic blood pressure (BP) separately in the daytime and night-time,
      isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E)
      to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall
      thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was
      also calculated. Eleven overweight non-apnoeic normal subjects matched for age
      were used as the control group. RESULTS: Our results showed that the patient
      group exhibited, before treatment, LV diastolic, but not systolic, dysfunction
      compared with the normal group (IVRT = 94.3 +/- 11.6 ms, p < 0.05; E/A = 0.94 +/-
      0.26, p < 0.02; SF = 39.9 +/- 4.1%, not significant (NS); IVST = 9.9 +/- 1.2 mm,
      NS; PWT = 8.3 +/- 1.2 mm, NS). Moreover, the patient group developed diastolic
      hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 +/-
      9.2 mm Hg, BP/diastolic/night-time = 90.3 +/- 10.7 mm Hg). After 12-14 weeks of
      nCPAP treatment (no change in body mass index), significant improvement in LV
      diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 +/- 8.8
      ms, p < 0.05; E/A = 1.07 +/- 0.3, p < 0.05; BP/diastolic/daytime = 86.3 +/- 5.5
      mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 +/- 8. 6 mm Hg, p < 0.05) in our
      patient group. CONCLUSIONS: We conclude that repetitive apnoeas/hypopnoeas are
      very important factors in the development of both LV diastolic dysfunction and
      diastolic systemic hypertension in patients with OSA syndrome. Treatment with
      nCPAP leads to significant improvement in both ventricular function and systemic
      hypertension.

PMID- 10940789
TI  - Airflow limitation in Japanese smokers: significance of serum neutrophil
      elastase/alpha(1)-proteinase inhibitor ratio and FEV(1) (%pred) adjusted by pack
      years.
AB  - BACKGROUND: In spite of the known role of cigarette smoking in the development of
      airflow limitation (AL), fewer than 20% of smokers actually develop chronic
      obstructive pulmonary disease (COPD). OBJECTIVES: We examined how smoking
      histories and indices in blood are related to the degree of AL in asymptomatic
      smokers in order to determine whether they can predict the development of AL.
      METHODS: Spirometry and peripheral blood tests were examined in 433 Japanese
      asymptomatic current smokers at the initial examination. Forced expiratory volume
      in 1 s (FEV(1)) was measured periodically for 2 or more years (2-13 years) in 66
      of the subjects. RESULTS: AL defined as an FEV(1)/vital capacity of less than
      0.7, was found in 11.3% (49 of 433) of the smokers. Pack-years of smoking, serum
      amounts of alpha(1)-proteinase inhibitor, and serum procollagen III peptide
      activities were correlated with the degree of AL. Fifteen percent (10 of 66) of
      subjects underwent rapid declines in FEV(1) that were found to be related not
      with smoking amounts or initial FEV(1), but with low FEV(1) (%pred) adjusted by
      pack-years and an elevated serum neutrophil elastase/alpha(1)-proteinase
      inhibitor ratio. These results suggest that smokers with a low FEV(1) out of
      proportion to pack-years are susceptible smokers at a high risk of developing
      COPD, and further, that increased proteinase burden relative to antiproteinase
      activity may contribute to the development of COPD. CONCLUSIONS: We conclude that
      the serum neutrophil elastase/alpha(1)-proteinase inhibitor ratio and FEV(1)
      (%pred) adjusted by pack-years can be reliable predictors of the development of
      COPD.

PMID- 10940790
TI  - Effect of thoracic sympathectomy on arm and leg exercise capacity and on lung
      function.
AB  - BACKGROUND: Thoracic T(2-4) sympathectomy (TS) relieves palmar hyperhidrosis.
      These same roots innervate the heart and the lung. Thoracoscopic TS minimizes
      damage to the chest wall so that the effect of sympathectomy itself on these
      organs can be studied. We attempted to determine whether attenuated sympathetic
      output affects arm or leg exercise tolerance and lung function in young adults
      who underwent this operation. METHODS: Seven subjects, aged 17-30 years, had lung
      function tests (water spirometer, Godart, Holland), and leg and arm maximal
      exercise (CPX, MedGraphics, USA), before and 3-6 months after TS. RESULTS: After
      TS, resting and exercise heart rate and blood pressure were reduced. Baseline leg
      and arm peak O(2) uptake, 2.08 (0.6) and 1.44 (0.5) liters/min, respectively,
      were not different from the post-TS values, 2.06 (0.7) and 1.54 (0.5) liters/min
      (nonsignificant). Post-TS lung functions were not significantly reduced.
      CONCLUSION: Thoracoscopic T(2-4) sympathectomy does not lead to a clinically
      important fall in lung function and does not compromise arm or leg exercise
      capacity. Therefore, TS can be done safely in young subjects with palmar
      hyperhidrosis.

PMID- 10940791
TI  - Rebreathing K(CO) and single breath K(CO) measured at the same mean alveolar
      volume reveal a physiological relationship between unequal diffusion and unequal
      ventilation in normal subjects.
AB  - BACKGROUND: The single breath (SB) method for determining the transfer factor for
      carbon monoxide is influenced by an unequal distribution of diffusion and
      ventilation. The rebreathing (RB) method is thought not to be influenced by these
      inequalities. Therefore, a comparison of the results of the two methods enables
      us to investigate unequal ventilation and diffusion. We have previously shown
      that even in normal subjects unequal ventilation influences the relation between
      the transfer factor as measured by the RB method and by the SB method.
      OBJECTIVES: To investigate to what extent unequal diffusion influences the
      relation between the RB and SB transfer factor in normal subjects. METHODS:
      Measurements were performed in 8 normal subjects. Differences in alveolar volume
      as measured by the RB and SB method were prevented from influencing the results
      by comparing the RB and SB transfer factor per liter of alveolar volume, i.e. the
      RB and SB Krogh factor, instead of the RB and SB transfer factor. The effect of
      the known dependence of the Krogh factor on inspired volume was prevented by
      measuring the SB Krogh factor at an inspired volume equal to the mean inspired
      volume of the RB measurement. This SB Krogh factor was compared with the RB Krogh
      factor calculated as the quotient of the RB transfer factor and the mean alveolar
      volume during the RB measurement. RESULTS: This RB Krogh factor was always larger
      than the corresponding SB Krogh factor. The difference was significant (p =
      0.006). A high percentage (80%) of the variance in the quotient of the two Krogh
      factors, which can be considered as a parameter for unequal diffusion, was
      explained by the variance in the quotient of the mean RB volume and the
      corresponding SB volume. The latter quotient is a measure of unequal ventilation.
      CONCLUSIONS: The finding suggests a physiological relation between unequal
      diffusion and unequal ventilation. A plausible explanation was found in the
      decrease of the Krogh factor with an increasing ratio of inspired volume to
      residual volume for each part of the lung separately. The consequence is that in
      the absence of unequal ventilation the RB transfer factor is equal to the SB
      transfer factor measured at an inspired volume equal to the mean RB inspired
      volume.

PMID- 10940792
TI  - Significance of the interleukin-1 receptor antagonist/interleukin-1 beta ratio as
      a prognostic factor in patients with pulmonary sarcoidosis.
AB  - BACKGROUND: Various factors such as serum angiotensin-converting enzyme (sACE)
      activity, bronchoalveolar lavage (BAL) fluid lymphocyte percent, CD4/CD8 ratio,
      and shadows on chest radiograph have been identified as indexes of disease
      activity in patients with sarcoidosis. However, it remains to be confirmed
      whether these factors can predict clinical outcomes. OBJECTIVE: To examine
      whether the interleukin-1 receptor antagonist (IL-1ra)/IL-1 beta ratio can
      predict the clinical course, we prospectively followed the clinical courses of 30
      patients with pulmonary sarcoidosis 4 years after measurement of immunoreactive
      amounts of IL-1ra or IL-1 beta in the culture supernatants obtained from BAL
      fluid macrophages. METHODS: Immunoreactive amounts of IL-1ra or IL-1 beta were
      measured using ELISA. Changes in pulmonary function, sACE activity, and shadows
      on chest radiographs during observation periods were evaluated as markers of
      changes in disease activity. RESULTS: We found that the patients whose shadows on
      chest radiographs showed improvement had a higher molar IL-1ra/IL-1 beta ratio
      than the patients whose shadows persistently remained 4 years after BAL
      examination (p < 0.05). The molar ratio was found to be positively correlated
      with improvement of percent vital capacity (p < 0.05) and negatively correlated
      with the ratio of sACE activity at the time of the last observation to sACE
      activity at the time of BAL (sACE(LAST)/sACE(BAL), p < 0.01). The
      sACE(LAST)/sACE(BAL) ratio was significantly lower in patients whose shadows on
      chest radiographs decreased than in those whose shadows remained unchanged (p <
      0.005). CONCLUSION: The IL-1ra/IL-1 beta ratio in the BAL fluid macrophage
      culture supernatants in patients with pulmonary sarcoidosis could be a useful
      marker in predicting the persistence of granulomatous lesions (chronicity).

PMID- 10940793
TI  - Circulating cytokeratin 8:anti-cytokeratin 8 antibody immune complexes in sera of
      patients with pulmonary fibrosis.
AB  - BACKGROUND: It has been suggested that the humoral immune system plays a role in
      the pathogenesis of idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis
      associated with collagen vascular disorders (PF-CVD). Although circulating immune
      complexes in patients' sera have been suggested, none of the antigens have been
      characterized. OBJECTIVES: The purpose of this study is to characterize the
      antigen of the immune complexes in patients' sera of pulmonary fibrosis. METHODS:
      As we previously established that one of the antibodies against A549 cells (lung
      alveolar type II cells) was anti-cytokeratin 8 (CK8), we confirmed the existence
      of anti-CK8 antibody in patients' sera by Western immunoblot. In addition, we
      tried to demonstrate circulating CK8:anti-CK8 immune complexes in patients' sera
      by Western immunoblot. Furthermore, we established an enzyme-linked immunosorbent
      assay to quantitate CK8:anti-CK8 immune complexes. RESULTS: In patients with
      pulmonary fibrosis, anti-CK8 antibodies were clearly demonstrated in sera by
      Western immunoblot. In addition, circulating CK8:anti-CK8 immune complexes were
      also clearly demonstrated by Western immunoblot. It was possible to establish
      ELISA to quantitate CK8:anti-CK8 immune complexes. If the cutoff value, which was
      determined based on the highest value of normal volunteers, was introduced, high
      CK8:anti-CK8 antibody complexes were demonstrated in 9 of 31 patients (29.0%)
      with IPF and PF-CVD. CONCLUSIONS: This is the first study to clarify the antigen
      of the circulating immune complex in sera of patients with IPF. These results
      suggest that circulating CK8:anti-CK8 immune complexes may have played a role in
      the process of lung injury in pulmonary fibrosis.

PMID- 10940794
TI  - Clinical features associated with a delayed diagnosis of cystic fibrosis.
AB  - BACKGROUND: The majority of patients with cystic fibrosis (CF) are diagnosed in
      the first decade of life. In a small number of patients, the diagnosis is not
      made until later. OBJECTIVE: In this study, the clinical and genetic features of
      patients diagnosed after the age of 10 were examined. METHODS: All living
      patients in Northern Ireland diagnosed prior to 1983, when neonatal screening was
      introduced, were studied. A total of 103 patients were identified of whom 18 were
      diagnosed after the age of 10. The relationships between late diagnosis and
      clinical presentation, sputum microbiology, pancreatic sufficiency, nutritional
      status, genotype and distance from the regional CF centres was determined by
      multiple regression analysis. RESULTS: All 18 late-diagnosed patients had a sweat
      (chloride >70 mmol/l). Late diagnosis was significantly related to carriage of
      the R117H mutation (r(2) = 0.45) and pancreatic sufficiency (r(2) = 0.37). There
      was a weak relationship with pulmonary function (r(2) = 0.09). CONCLUSIONS: In
      Northern Ireland, late diagnosis in mainly associated with pancreatic function
      and carriage of the R117H mutation.

PMID- 10940795
TI  - Spontaneous pneumomediastinum in 33 patients: yield of chest computed tomography
      for the diagnosis of the mild type.
AB  - BACKGROUND: Spontaneous pneumomediastinum (SPM) usually occurs in young people
      without an apparent precipitating factor or disease. Although there have been
      many studies focused on the clinical features and standard chest X-ray (CXR)
      findings of SPM, few have reviewed the chest computed-tomographic (CT) findings.
      OBJECTIVES: We assessed SPM using CXR and CT, and the relation between them.
      METHODS: We evaluated 33 patients (26 males) diagnosed with SPM on the basis of
      symptoms and chest radiological findings. RESULTS: Three patients showed normal
      CXR but a diagnostic CT scan. Seven showed mild pneumomediastinum on CXR. In
      these 10 patients, pneumomediastinum was easily detected by chest CT. Moderate
      and severe SPM were easily detected by both CXR and CT. CONCLUSIONS: These
      findings suggested that CXR alone poorly detected approximately 30% of SPM and
      that chest CT scan was needed to make the diagnosis in these cases. It seems
      likely that SPM is underdiagnosed by 30% or more in clinical practice.

PMID- 10940796
TI  - Prognosis of bronchial artery embolization in the management of hemoptysis.
AB  - BACKGROUND: Bronchial artery embolization (BAE) is a well-accepted and widely
      used treatment modality for the management of massive and recurrent hemoptysis.
      However, few reports have previously investigated the long-term results.
      OBJECTIVES: To investigate the prognosis of patients with hemoptysis who had
      undergone BAE. METHODS: Twenty-two patients with hemoptysis underwent BAE. The
      underlying diseases included bronchiectasis in 9, aspergillosis in 3, chronic
      bronchitis in 2, idiopathic bronchial bleeding in 4, and other diseases in 4. The
      follow-up period ranged from 25 to 88 months (median 47 months). RESULTS: After
      the initial BAE, 11 of 22 (50%) patients had re-bleeding (5 patients with
      hemoptysis and 6 patients with minor hemosputa). Among them, 1 patient suffered
      from recurrent massive hemoptysis and died from airway obstruction within 1 month
      after BAE. In addition, 10 of these 11 (90.9%) patients experienced recurrent
      airway bleeding within 3 years after BAE. Recurrent cases of hemoptysis were seen
      in 6 of 22 patients (27.3%) within 3 years and no case recurred later than 3
      years after BAE. A recurrence of hemoptysis was frequently seen in patients with
      either bronchiectasis or pulmonary-bronchial artery (P-B) shunt. Although BAE is
      an effective treatment for the immediate control of hemoptysis, 5 of the patients
      experienced recurrent bleeding in the long-term follow-up. CONCLUSIONS: It is
      important to follow-up such patients until 3 years after initial BAE, especially
      when either ectatic changes of the bronchi on a CT scan or a P-B shunt on
      angiographic findings are detected.

PMID- 10940797
TI  - Placebo-controlled study of inhaled budesonide on indices of airway inflammation
      in bronchoalveolar lavage fluid and bronchial biopsies in cross-country skiers.
AB  - BACKGROUND: Asthma-like symptoms, methacholine hyperresponsiveness, use of
      inhaled steroids, airway inflammation, and increased tenascin expression in the
      reticular basement membrane have been reported in competitive cross-country
      skiers. OBJECTIVE: To investigate the effect of inhaled budesonide, 400 mug twice
      daily, on indices of airway inflammation in 'ski asthma', defined as asthma-like
      symptoms within the previous year and bronchial hyperresponsiveness to
      methacholine. METHODS: A randomised double-blind placebo-controlled parallel
      group bronchial biopsy and bronchoalveolar lavage (BAL) study of 25 (19 male)
      competitive cross-country skiers (mean age 18 (16-20) years for a mean (range)
      treatment period of 22 (10-32) weeks over the competitive season. RESULTS: No
      changes were seen regarding cellular inflammation in the bronchial mucosa or
      tenascin expression. In the BAL fluid, both groups had a significant decrease in
      activated T-suppressor (CD8) lymphocytes and an increase in macrophages, with no
      differences across the groups. Within the budesonide group, there was a decrease
      in IL2 receptor-activated T-helper lymphocytes and an improvement in FEV(1).
      Asthma-like symptoms were unchanged in 17 (68%) skiers. Methacholine provocation
      test was negative in 15 subjects, and remained positive in 5 subjects in each
      group. The improvement in bronchial responsiveness occurred in both groups and
      was not accompanied by a decrease in cellular inflammation. CONCLUSIONS: We were
      unable to show any clear beneficial effect of budesonide in 'ski asthma'. As
      changes in training intensity probably accounted for the spontaneous improvement
      in bronchial responsiveness, more attention should be directed at reducing
      environmental stress to the airways than at attempting pharmacological modulation
      of induced inflammatory changes.

PMID- 10940798
TI  - Diagnostic accuracy of pleural fluid polymorphonuclear elastase in the
      differentiation between pyogenic bacterial infectious and non-infectious pleural
      effusions.
AB  - BACKGROUND AND OBJECTIVES: To establish the diagnostic accuracy of the markers of
      neutrophil activity (elastase and lysozyme) determined in pleural fluid, for
      differentiating between pyogenic bacterial infectious and non-infectious pleural
      effusions. PATIENTS AND METHODS: At our tertiary referral teaching hospital, 160
      patients over 14 years with pleural effusion (PE), classified as pyogenic
      bacterial infectious (41 parapneumonic complicated, 32 parapneumonic non
      complicated) and non-infectious (32 neoplasm and 55 undiagnosed pleural exudates)
      were examined in a prospective study. Polymorphonuclear elastase (PMN-E) was
      determined by an immunoactivation method and lysozyme by a turbidimetric method.
      Receiver operating characteristic (ROC) curves were used to evaluate diagnostic
      accuracy. RESULTS: Pleural fluid PMN-E was the biochemical marker that best
      differentiated between pyogenic bacterial infectious and non-infectious PE. The
      ROC area under the curve (AUC) for PMN-E was 0.8276. A PMN-E value over 230
      microg/l diagnosed infectious PE with a specificity of 0.81 and a sensitivity of
      0.74. The ROC AUC for proteins plus lactate dehydrogenase was 0. 7430.
      Differences between the two ROC curves were significant (p = 0. 032). After
      excluding purulent parapneumonic complicated PE, the sensitivity of a pleural
      fluid PMN-E value equal to or greater than 230 microg/l was 0.64 and the
      specificity 0.81. CONCLUSIONS: Pleural fluid PMN-E was the marker that best
      differentiated infectious from non-infectious PE, and PMN-E values lower than 230
      microg/l suggest non-infectious PE.

PMID- 10940799
TI  - Pleural SC5b-9: a test for identifying complicated parapneumonic effusions.
AB  - BACKGROUND AND OBJECTIVES We have tested whether the complement activation
      products SC5b-9 and C3a-desArg are useful to distinguish complicated (CPE) from
      uncomplicated parapneumonic effusions (UPE). DESIGN: A total of 66 patients were
      enrolled in the study: 5 with empyema, 19 with CPE, 12 with UPE, and 30
      transudates who served as controls. SC5b-9 and C3a-desArg were measured by
      commercial ELISA tests, and their performances were evaluated using receiver
      operating characteristic (ROC) analysis. RESULTS: Patients with CPE had higher
      mean levels of pleural SC5b-9 (8,218 microg/l) and C3a-desArg (8,790 microg/l)
      than those with UPE (2,227 and 3,772 microg/l, respectively; p < 0.0001), whereas
      concentrations in the latter were comparable with controls for the SC5b-9 test.
      Empyemas had a wide range of pleural complement activation product values.
      Pleural SC5b-9 and C3a-desArg showed very high diagnostic accuracy in the
      diagnosis CPE (90.3 and 77.8%, respectively) when corresponding cutoff points of
      2,000 and 4,000 microg/l were used. In a stepwise logistic regression analysis,
      the combination of SC5b-9 >/=2,000 microg/l, LDH >/=1,000 U/l and a pleural
      polymorphonuclear percentage >/=85% provided the highest discriminative power for
      the diagnosis of CPE (area under ROC curve 0.97). CONCLUSION: This pilot study
      suggests that measurement of pleural SC5b-9 can be useful in the workup of
      patients with a parapneumonic effusion in order to differentiate CPE from UPE.

PMID- 10940800
TI  - Effect of the airway epithelium on the contraction of rat isolated trachea under
      conditions of low temperature.
AB  - BACKGROUND: The exposure of the airways to low temperature (LT) is a well-known
      trigger of bronchoconstriction and asthma. However, the mechanisms involved in
      this response are not well understood. In particular, the specific role of the
      airway epithelium in the response to LT has not been well established. OBJECTIVE:
      The purpose of this work is to study the regulatory role of the airway epithelium
      in the contractile response of the rat trachea under conditions of LT. METHODS:
      Isolated rat tracheas were stimulated with acetylcholine (ACH) at 37 and 18
      degrees C, and dose-response curves were generated in epithelium-intact or
      epithelium-denuded conditions. EC(50) and E(max) were determined under these
      conditions. RESULTS: Epithelium denudation at 37 degrees C, increases the
      tracheal sensitivity to ACH, (EC(50) from 5.9 to 2.6 microM, p = 0. 003). The
      effects of denudation were even more pronounced at 18 degrees C. E(max) was
      significantly decreased under these conditions. Exposure of intact tracheas to 18
      degrees C also produced a significant increase in tracheal sensitivity (EC(50)
      from 5.9 to 1.5 microM, p = 0.0004), although no changes in E(max) were noted.
      CONCLUSIONS: These results strongly suggest that the airway epithelium diminishes
      the sensitivity of the airway smooth muscle to ACH at 37 and 18 degrees C, and
      that it is also needed to observe the maximal contractile response under LT
      conditions. Therefore, the spasmogenic effect of low temperature is significantly
      potentiated by the absence of airway epithelium.

PMID- 10940801
TI  - Pleural Kaposi's sarcoma: a potentially overlooked manifestation.

PMID- 10940802
TI  - Diffuse alveolar hemorrhage following thrombolytic therapy for acute myocardial
      infarction.
AB  - We describe a 66-year-old patient with hemoptysis, a drop in hematocrit,
      hypoxemia and new bilateral alveolar infiltrates after receiving streptokinase
      for acute myocardial infarction. Markedly increased carbon monoxide diffusion
      capacity suggested a diagnosis of alveolar hemorrhage. Underlying conditions
      included congestive heart failure. The patient recovered uneventfully within 7
      days of conservative treatment. Alveolar hemorrhage is a rare and often
      unrecognized life-threatening complication of thrombolytic therapy. Particular
      attention should be paid to the pulmonary status of patients with congestive
      heart failure scheduled to receive thrombolytic therapy.

PMID- 10940803
TI  - Absence of central microtubules and transposition in the ciliary apparatus of
      three siblings.
AB  - We studied the cases of three siblings with a history of chronic bronchitis and
      infertility. The electron-microscopic investigation of the tracheal and bronchial
      biopsies showed a ciliary defect consisting in the absence of the central
      microtubules and the transposition of a peripheral doublet. This is a rare and
      infrequently reported abnormality included in the primary ciliary diskinesia
      syndrome.

PMID- 10940804
TI  - Systemic to pulmonary fistulas in Hodgkin's disease.
AB  - Systemic to pulmonary fistula is an unusual entity and its association with
      hematological diseases like Hodgkin's is extremely rare. We present a case of a
      26-year-old woman with a thoracic mass and large arteriovenous fistula. The
      diagnosis of Hodgkin's disease, nodular sclerosis, was obtained by a biopsy of
      the supraclavicular lymph node. We achieved an excellent response after combined
      treatment with chemotherapy, radiotherapy and arterial embolization with complete
      disappearance of the mass.

PMID- 10940805
TI  - Deciduoid pleural mesothelioma affecting a young female without prior asbestos
      exposure.
AB  - Pleural mesothelioma is commonly associated to asbestos exposure. A 40-year-old
      woman is described who presented with shortness of breath. She had a smoking
      history but no history of asbestos exposure. Chest radiography and computed
      tomography showed a large tumour on the right lower lung. An open pleural biopsy
      was performed. A metastatic adenocarcinoma of the pleura was primarily diagnosed.
      The tumour progressed and after surgical excision an accurate histological and
      immunohistochemical examination was performed. It revealed a pleural mesothelioma
      with a deciduoid differentiation that has not been described before.

PMID- 10940806
TI  - Pulmonary migratory infiltrates and pachypleuritis in a patient with Crohn's
      disease.
AB  - Crohn's disease can be associated with several respiratory manifestations. We
      report here a case of pulmonary migratory infiltrates associated with bilateral
      pleural thickening and peripheral eosinophilia. The histopathological findings
      show an association of necrotizing nodules, eosinophilic infiltration in the non
      abscessed lung tissue, areas of non-caseating epithelioid granulomas, and an
      extensive pleural fibrosis. The different histopathological findings are detailed
      and the responsibility of either Crohn's disease or treatment by mesalazine is
      discussed.

PMID- 10940807
TI  - Nasal continuous positive airway pressure and weight loss improve swallowing
      reflex in patients with obstructive sleep apnea syndrome.
AB  - We have recently reported that swallowing reflex is impaired in patients with
      obstructive sleep apnea syndrome (OSAS). However, the effects of OSAS treatment
      on swallowing function in these patients have not been reported. Here we report 2
      cases of OSAS in whom swallowing reflex was impaired before the start of nasal
      continuous positive airway pressure (NCPAP) and improved 1 year after NCPAP.
      These cases suggest that impaired swallowing reflex may be reversible by OSAS
      treatment.

PMID- 10940808
TI  - Organizing pneumonia related to common variable immunodeficiency. case report and
      literature review.
AB  - A 68-year-old woman suffering from common variable immunodeficiency (CVI)
      developed a typical picture of organizing pneumonia. Causative factors other than
      CVI were eliminated. Several antibiotic regimens failed to improve the patient's
      condition, while the clinical manifestations rapidly disappeared under steroid
      therapy, with complete radiological recovery, but relapsed after steroid
      withdrawal. Finally, organizing pneumonia was definitely demonstrated by
      pathological findings obtained by open lung biopsy. Interestingly, pathological
      examination exhibited two other well-known CVI-associated lesions, i.e. benign
      lymphoid hyperplasia and noncaseating granuloma. In view of reports in the
      literature, we speculate that these different histological patterns could have
      resulted in a spectrum of symptomatic CVI-associated pulmonary disorders that
      improved under steroid therapy.

PMID- 10940810
TI  - Wegener's granulomatosis with unilateral renal atrophy.

PMID- 10940809
TI  - Recurrent pleural effusion and a mediastinal mass.

PMID- 10940811
TI  - Maximal cardiorespiratory capacity in young sedentary male chronic smokers.

PMID- 10940812
TI  - The pig as an experimental animal model of percutaneous permeation in man:
      qualitative and quantitative observations--an overview.
AB  - The pig has been a well-recognized experimental animal in biomedical research for
      many centuries. Physiological and anatomical similarities between man and pig
      made this animal a good model for man in many research areas. Pharmacological and
      toxicological research on the skin is often based on knowledge of skin absorption
      and percutaneous permeation. Anatomical, physiological and biochemical
      similarities are cited and various uses of the pig as a model for man in the
      investigation of skin permeation are reviewed. Further, several isolated organ
      models are reviewed. The importance of full details of the experimental animal,
      namely its age, sex, breed, size (weight) and body region, is emphasized.

PMID- 10940814
TI  - Assessment of toxic potential of industrial chemicals using a cultured human
      bioartificial skin model: production of interleukin 1alpha and
      hydroxyeicosatetraenoic acids.
AB  - Cytotoxicity assays using artificial skin are proposed as alternative methods for
      in vitro tests to minimize animals used in ocular and dermal irritation testing.
      The responses of the artificial skins were studied to a well-characterized
      chemical irritant, such as toluene, glutaraldehyde and sodium lauryl sulfate
      (SLS), and a nonirritant, such as polyethylene glycol. The evaluation of
      irritating and nonirritating test chemicals was also compared with responses seen
      in human dermal fibroblasts and human epidermal keratinocytes grown in monolayer
      culture. The responses monitored included the MTT mitochondrial functionality
      assay. In order to better understand the local mechanisms involved in skin damage
      and repair, the productions of several mitogenic proinflammatory mediators such
      as interleukin-1alpha (IL-1alpha), 12-hydroxyeicosatetraenoic acid (12-HETE) and
      15-HETE were investigated. Dose-dependent increases in the levels of IL-1alpha
      and HETEs were observed in the underlying medium of the skin systems exposed to
      two skin irritants, glutaraldehyde and SLS. The results of the present study show
      that both human artificial skins can be used as efficient testing models for the
      evaluation of skin toxicity in vitro and for screening the contact skin irritancy
      in vitro.

PMID- 10940813
TI  - Preview of potential therapeutic applications of leukotriene B4 inhibitors in
      dermatology.
AB  - This article reviews the mechanisms and potential therapeutic uses of compounds
      with inhibitory effects on leukotriene B4 (LTB4) production or its activity, and
      focuses on compounds that have been shown in animal and/or human studies to have
      potential efficacy in treating dermatological disorders. These compounds, many of
      which are not familiar to many dermatologists, include inhibitors of 5
      lipoxygenase such as ETH615, 15-hydroxyeicosatetraenoic acid, leflunomide,
      linetastine, lonapalene, MK886, R-68151 and zileuton, and antagonists of LTB4
      such as SC53228, SC50605, SC51146 and VML295. The purpose of this paper is to
      introduce our colleagues to these potentially useful compounds currently in
      preclinical or early clinical testing.

PMID- 10940815
TI  - Investigation of the stability of coated titanium microparticles used in
      sunscreens.
AB  - Due to its UV-light-absorbing properties, titanium dioxide is used in many
      sunscreen products. However, concern has been raised about a possible
      photocatalytic activity of titanium dioxide on living tissues. To reduce
      potential adverse effects, titanium dioxide used in cosmetic preparations is
      often coated. The coating should be stable under conditions of use. In order to
      verify the coating stability, sunscreen-grade-coated titanium microparticles were
      investigated by laser-induced plasma spectroscopy. No changes in the mechanical
      stability of the coated microparticles could be detected during the manufacturing
      and penetration of the sunscreen. Applying strong forces on the microparticles by
      centrifugation, exceeding by far in use conditions, resulted only in small
      changes in the coating.

PMID- 10940816
TI  - Structural modifications in the stratum corneum by effect of different
      solubilizing agents: a study based on high-resolution low-temperature scanning
      electron microscopy.
AB  - The action of different solubilizing agents (chloroform-methanol mixtures and the
      nonionic surfactant octyl glucoside, OG) on the structural organization of the
      stratum corneum (SC) was investigated by means of the double-layer high
      resolution low-temperature scanning electron microscopy technique. Chloroform
      methanol mixtures were able to remove mainly the lipid without a significant loss
      of cohesion in the SC tissue. However, OG treatment caused a partial
      disaggregation of the corneocytes and their envelopes and, at a macroscopic
      level, a loss of cohesion in the whole SC tissue. As for lipid domains, after OG
      treatment the formation of rough structures was detected, probably associated
      with the disorder in the lipid lamellae. The formation of these new structures
      could be attributable to the interaction of the lipids with the proteins
      liberated from the corneocytes. Hence, a direct correlation may be established
      between the preservation of the structure of the corneocytes and the corneocyte
      envelope and the cohesion of the whole SC tissue.

PMID- 10940817
TI  - Dithranol in a cream preparation: disperse or dissolve?
AB  - In the search for the ideal dithranol cream preparation for short-contact
      treatment of psoriasis, we investigated the clinical efficacy, side effects and
      patient appreciation of two dithranol cream preparations (cream A and B) in a
      double-blind left-right comparing study. Dithranol was dissolved at preparation
      in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1
      year, while cream B has a much shorter shelf life (several months). Ten patients
      with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact
      regimen. The clinical efficacy was monitored by scoring of erythema, induration,
      scaling and involved area (PASI); skin irritation was scored visually, and
      patient appreciation was evaluated by means of a multiple-choice questionnaire.
      Dispersion of dithranol in a cream was associated with less irritation and less
      discoloration of the skin, and its efficacy was comparable with that of the cream
      in which the dithranol was dissolved. As the dispersed dithranol formulation is
      easier to be manufactured, its quality will be less depending on the pharmacist's
      experience and equipment, and so more reliable. Besides, it will be less
      expensive to prepare. We advise to use this formulation for short-contact
      treatment.

PMID- 10940818
TI  - Penetration enhancers assessed by corneoxenometry.
AB  - Chemical enhancers abating the barrier function of the stratum corneum act in a
      number of ways. Their relative effects in mixtures are notoriously difficult to
      determine. Corneoxenometry is a bioassay where xenobiotic interactions with
      corneocytes are assessed using reflectance colorimetry. It was used to evaluate
      comparatively the effects of ethanol and laurocapram at various dilutions. In
      addition, a 10% propylene-glycol-based gel supplemented with N-acetyl-L-cysteine,
      urea and salicylic acid in various concentrations was tested. The relative index
      or irritancy (RII) was calculated for each formulation. RII is a surrogate marker
      of lipid removal and disorganization, and of protein denaturation in the stratum
      corneum. It is likely a good predictor for barrier function alterations and
      represents a cheap and rapid alternative to animal testing.

PMID- 10940819
TI  - Tazarotene induces epidermal cell differentiation in the mouse tail test used as
      an animal model for psoriasis.
AB  - Disturbed epidermal proliferation and keratinization are major features of
      psoriatic skin lesions. The so-called mouse tail test is known as an animal model
      to evaluate the antipsoriatic efficacy of topical drugs with regard to the
      induction of orthokeratosis. The purpose of the present study was to investigate
      the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail
      test in a direct comparison to dithranol representing a classical topical
      antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel
      (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and
      methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal
      histological sections were prepared from the tail skin, and the degree of
      orthokeratosis was determined by measuring the horizontal length of the fully
      developed granular layer within an individual scale in relation to its total
      length according to a method originally described by Bosman and co-authors. The
      degree of orthokeratosis was significantly (p < or = 0.05) increased by 0.1%
      tazarotene (87+/-20%), 1.0% dithranol (75+/-26%), 0.05% tazarotene (59+/-27%),
      and 0.05% tretinoin (23+/-13%) as compared to untreated (11+/-6%) and
      methylcellulose hydrogel-treated (13+/-6%) controls. Under the conditions of the
      mouse tail test, tazarotene showed a strong potency to induce orthokeratosis.
      With regard to clinically relevant concentrations this effect was even more
      pronounced than that observed for dithranol.

PMID- 10940820
TI  - Synergistic activity of benzoyl peroxide and erythromycin.
AB  - BACKGROUND: Benzoyl peroxide (BP) is the most widely used topical agent for acne
      since its introduction in the 1960s. Concomitant topical treatment of BP and
      erythromycin is stated to be superior to BP alone. However, no synergistic
      activity has been found with this combination. Instead, such combination
      therapies are hypothesized to gain their efficacy by the coupled action of two
      effective treatments. The antibiotic kills all susceptible bacteria and the BP
      eliminates the resistant strains. OBJECTIVE: The purpose was to compare radical
      production by BP alone and with various antibiotics to determine whether certain
      antibiotics increase radical formation by BP, as the antibacterial activity of BP
      may correlate with the amount of radicals it forms. METHODS: Polymerization of
      tetraethylene glycol dimethacrylate was used as a test of BP radical activity.
      RESULTS: The results suggest that radical activity increases upon addition of
      certain antibiotics, such as erythromycin, to a solution of BP. CONCLUSION:
      Radical activity of BP in tetraethylene glycol dimethacrylate is increased when
      tested in consort with several antibiotics, such as the macrolides. We propose
      that the tertiary amines contained on certain antibiotics are responsible for
      catalysis of BP radical formation. If increased radical formation correlates with
      enhanced biological effect, then these data reveal the possibility of a
      biological synergism in mixtures of BP and antibiotics. An understanding of the
      mechanism of catalysis of BP radical formation by antibiotics may lead to the
      discovery of improved treatments for acne.

PMID- 10940821
TI  - Isolation of the Epstein-Barr virus in scirrhous gastric cancer by efficiency
      monitored representational difference analysis.
AB  - We applied an improved representational difference analysis (RDA), efficiency
      monitored RDA (EM-RDA), to analyze the genetic alterations of scirrhous gastric
      cancer. Clinical samples of this cancer are difficult to analyze genetically
      because of the large number of normal cells in the stroma. The entire 3rd
      difference product obtained from EM-RDA was subcloned. This is equivalent to the
      scirrhous gastric cancer DNA with the normal gastric tissue DNA subtracted from
      it. The difference clones, which were confirmed by Southern blot as being derived
      from the cancer, were sequenced. As a result, two difference clones were
      identified as DNA fragments of the Epstein-Barr virus (EBV). The existence of EBV
      in the scirrhous gastric cancer cells was proved by EBV-encoded small RNA 1 in
      situ hybridization. EM-RDA made it possible to detect the first case of EBV
      related gastric cancer in a young woman.

PMID- 10940823
TI  - Isolation and properties of human alpha-fetoprotein from HepG2 cell cultures.
AB  - A relatively rapid 3-step fractionation method has been developed for the
      isolation of human alpha-fetoprotein from culture fluids of HepG2 cells
      applicable to large volumes. The protein exists as a complex with lipids or
      lipoproteins but an ethanol precipitation step is effective in separating it.
      Yields of 50-60% can be obtained from culture fluid containing 30-40 microg/ml. A
      minor fraction that appears to be a proteolytic product of the AFP is present in
      the final product.

PMID- 10940822
TI  - Increased galectin-3 expression in gastric cancer: correlations with
      histopathological subtypes, galactosylated antigens and tumor cell proliferation.
AB  - Galectin-3 represents an endogenous galactoside-binding lectin which may be
      involved in tumor cell adhesion and proliferation. In order to evaluate its
      biological significance in human gastric cancer, we investigated its expression
      in the stomach of a large series of patients (n = 193) by immunohistochemical
      staining with the monoclonal antibody Mac-2. Compared to normal tissues, primary
      gastric adenocarcinomas showed a slight increase in galectin-3 expression.
      However, there was no correlation of membrane-bound and cytoplasmic galectin-3
      with histopathological differentiation parameters (according to the WHO and
      Lauren classifications) or tumor progression (as documented by pTNM staging).
      Nuclear galectin-3 reactivity was significantly stronger in diffuse-type cancer
      compared to the intestinal-type tumors. Galectin-3 binds to terminal
      GalNAcalpha(1-3) bound to polylactosamine chains and related glycotopes.
      Therefore, the strong coexpression of membrane/cytoplasmic galectin-3 with
      Griffonia simplicifolia agglutinin I (GSA I) binding sites (Galalpha1-3Gal-,
      GalNAcalpha-) on carcinoma cells seems to be interesting. On the other hand,
      nuclear galectin-3 immunoreactivity did not correlate with the incidence of Ki-67
      positive tumor cells. A prognostic value of galectin-3 regarding patient survival
      could not be established.

PMID- 10940824
TI  - Rat alpha-fetoprotein promoter and proximal enhancer direct expression of the nls
      lacZ reporter gene in embryonic yolk sac, gut, and eustachian canal of transgenic
      mice.
AB  - The alpha-fetoprotein (AFP) gene is expressed mainly in the yolk sac, liver and
      intestine during embryonic and fetal life. We have analyzed the activities of
      some of the rat AFP regulatory elements in vivo, using transgenic mice bearing
      the LacZ gene with a nuclear localization signal (nls-lacZ) placed under the
      control of the rat AFP promoter and the most proximal enhancer regions (from 
      3,127 to +102). Four of the six transgenic lines, with two genetic backgrounds,
      had highly specific reproducible patterns of transgene expression on embryonic
      days E10.5, E12 and E15. Analyses were performed on the whole embryo and
      histologically. There was nuclear staining in the yolk sac endodermal cells and
      in the epithelial cells of the intestine, indicating that the proximal enhancer
      and promoter drive expression in these cells where the AFP gene is actively
      transcribed. The pharyngo-tympanic canal was also stained in the transgenic
      embryos. But there was no expression of the lacZ transgene in the embryonic
      liver, indicating that additional sequences of rat genomic DNA are required for
      correct expression in the liver.

PMID- 10940825
TI  - Ascitic growth of a spontaneous transplantable T cell lymphoma induces thymic
      involution. 1. Alterations in the CD4/CD8 distribution in thymocytes.
AB  - We have previously shown that the progressive ascitic growth of a transplantable
      T cell lymphoma of spontaneous origin in a murine host, designated as Dalton's
      lymphoma (DL), induces the inhibition of various immune responses. In a quest to
      understand the mechanism(s) of tumor-growth-dependent immunosuppression, we were
      interested to investigate if the thymus, the center for the differentiation of
      immunocompetent T cells, undergoes any alteration concomitant with the growth of
      DL. Thus, DL was grown as an ascitic tumor in BALB/c mice for a period of 4 or 17
      days, designated as the early and late tumor stages, respectively, and the
      thymuses were examined immediately after sacrifice of the animals on the 4th or
      17th day of tumor transplantation. Progressive growth of DL was observed to be
      associated with thymic atrophy, as well as an involution of thymic organization
      and a depletion of cell mass. Histological sections of thymus from DL-bearing
      mice revealed a complete disintegration of the thymic architecture with a massive
      depletion of the cortical region and disappearance of the corticomedullary
      junctions. Flow cytometric analysis of alterations in the distribution of
      thymocytes revealed a decrease in CD4+CD8-, CD4-CD8+ and CD4+CD8+ cell
      populations, whereas the CD4-CD8- population showed an increase, suggesting an
      impairment in thymocyte differentiation at an early T cell maturation stage.
      Furthermore, tumor growth was shown to suppress the proliferation ability of
      thymocytes. Moreover, an increase in thymocytes of smaller size was also found
      with the progression of DL, which is an indication that a large fraction of
      thymocytes of a small, abnormal size could be apoptotic cells. Furthermore, the
      paper discusses the immunological implications of thymic atrophy in a host
      bearing a T cell lymphoma.

PMID- 10940826
TI  - Inhibitory effects of malotilate on in vitro invasion of lung endothelial cell
      monolayer by human oral squamous cell carcinoma cells.
AB  - We have previously reported that malotilate (MT) inhibited the invasion and
      metastasis of rat mammary carcinoma cells through the modification of host
      endothelial cells. In this study, we examined the inhibitory effects of MT on
      invasion of human cancer, using five oral squamous cell carcinoma cells (SAS, Ca9
      22 and HSC-2, -3 and -4). MT did not affect the growth of these tumor cells and
      the invasion of reconstituted basement membrane, Matrigel. In an in vitro
      invasion assay using rat lung endothelial (RLE) cells, invasion of tumor cells
      which had been treated with MT (10 ng/ml, 24 h) was not affected; however, when
      RLE cells had been treated with MT, invasion was significantly inhibited in three
      cell lines (SAS, Ca9-22 and HSC-4) and a tendency to inhibition was also observed
      in other cell lines. Electron-microscopical examination of the RLE monolayer
      treated with MT (MT-RLE) showed the development of gap and tight junction-like
      structures. Subsequently, junction-associated proteins, connexin 43, zonula
      occludin and desmoglein, were examined by Western blotting. Protein levels of
      connexin 43 and zonula occludin were elevated dose dependently, and connexin 43
      was chronologically enhanced by MT whereas desmoglein was not. The enhanced gap
      junctional communication of MT-RLE cells was observed in the scrape-loading assay
      using lucifer yellow CH. These results suggest that MT promotes the development
      of cell-to-cell adhesion, e. g. gap junction and tight junction in endothelial
      cells, resulting in the inhibition of invasion by the tumor cells.

PMID- 10940828
TI  - Humanitarian health tour in peru: A firsthand account

PMID- 10940829
TI  - President's message. The time has come... .

PMID- 10940827
TI  - Tumor anemia and thrombocytosis in patients with vulvar cancer.
AB  - The aim of our study was to determine the prevalence of tumor anemia and
      thrombocytosis in patients with vulvar cancer, and to evaluate the prognostic
      value or pretreatment hemoglobin (Hb) and platelet count regarding disease-free
      and overall survival of patients with vulvar cancer. We measured pretreatment Hb
      and platelet count in 62 patients with squamous cell vulvar cancer. The results
      were correlated to clinical data. Median Hb and platelet count in patients with
      vulvar cancer were 13.1 g/dl (range 8.3-16.2) and 268, 500/microl (range 88,000
      778,000), respectively. Cut-off levels of 12 g/dl and 300,000/microl were
      selected for tumor anemia and tumor thrombocytosis, respectively according to
      published criteria. Tumor anemia and tumor thrombocytosis were present in 30.6
      and 27.4% of patients with vulvar cancer, respectively. In a univariate analysis
      tumor stage and tumor thrombocytosis were significantly associated with a
      shortened disease-free (log-rank test, p < 0.001 and p = 0. 003, respectively)
      and overall survival (log-rank test, p < 0.001 and p < 0.001, respectively).
      Tumor anemia was not associated with a shortened disease-free, but with a
      shortened overall survival of patients with vulvar cancer (log-rank test, p = 0.1
      and p = 0.002, respectively). A multivariate Cox regression model considering
      tumor stage, tumor anemia, and tumor thrombocytosis showed, however, that
      pretreatment Hb and platelet count did not confer additional prognostic
      information to that already obtained by the established prognosticator tumor
      stage on disease free (multivariate Cox regression model, p = 0.8, p = 0.2, and p
      = 0.003, respectively) and overall survival (multivariate Cox regression model, p
      = 0.4, p = 0. 5, and p = 0.04, respectively). Pretreatment tumor anemia and tumor
      thrombocytosis were associated with a poor prognosis, but were not an independent
      predictor of outcome in patients with vulvar cancer.

PMID- 10940830
TI  - One...in a million moms.

PMID- 10940832
TI  - Would you allow an agitated irate minor to leave?

PMID- 10940831
TI  - Educational quandary: what background is best for emergency nurse educators?

PMID- 10940833
TI  - Nurse practitioner offers way to follow up with positive laboratory results after
      patients leave

PMID- 10940835
TI  - Organizing in the face of increasing demands on nursing

PMID- 10940834
TI  - More on customer service

PMID- 10940836
TI  - A 49-year-old man exhibiting combative and bizarre behavior.

PMID- 10940837
TI  - Emergency nurses' knowledge of pain management principles.
AB  - INTRODUCTION: The purpose of this study was to determine areas of emergency
      nurses' knowledge deficit regarding pain management, and to identify barriers to
      pain management as perceived by emergency nurses. METHODS: Data were collected
      anonymously in a mail survey using a 52-item knowledge questionnaire addressing
      pain management principles and asking emergency nurses (Illinois Emergency Nurses
      Association members) to rate various barriers as to how often they affect their
      practice. Questionnaires were mailed to all Illinois ENA members (n = 1000).
      RESULTS: Three hundred five emergency nurses' questionnaires were returned. A
      significant deficit existed on 2 domains of knowledge: understanding of the terms
      "addiction," "tolerance," and "dependence"; and knowledge of various
      pharmacologic analgesic principles. Nurses with a master's degree or higher, or
      those who attended a 1-day seminar on pain management, achieved statistically
      significantly higher scores. The 2 barriers identified by emergency nurses as the
      most common were the inability to administer medication until a diagnosis is made
      (53%), and inadequate assessment of pain and pain relief (48%) (the percentage
      indicates how often the emergency nurses believed the barrier was present in
      their practice). DISCUSSION: The data indicate that emergency nurses may not have
      a good understanding of the management of pain with drugs, or of such issues as
      risk of addiction.

PMID- 10940838
TI  - Routine pharyngeal cultures may not be useful in pediatric victims of sexual
      assault.
AB  - INTRODUCTION: This study was conducted to determine the usefulness of routine
      pharyngeal cultures in pediatric sexual assault victims. METHODS: A retrospective
      chart review was conducted to examine incidence data. The study was conducted in
      a 656-bed tertiary care hospital with 60,000 ED visits and approximately 350
      pediatric sexual assault examinations annually. Records of all pediatric sexual
      assault examinations completed between 12:01 AM January 1, 1994, and 12:01 AM
      January 1, 1997, were retrospectively reviewed for inclusion. Subjects were
      included if they were younger than 15 years and had a nonacute examination for a
      suspected sexual assault. The final sample included 370 females and 81 males
      (total n=451 children). Oral and anal cultures were obtained on all patients. In
      addition, female patients had vaginal cultures and male patients had penile
      cultures performed. Culture specimens were sent for detection of chlamydia and
      gonococcus organisms. RESULTS: Of the 451 sets of cultures examined, there were 6
      patients with one or more positive culture results. The 6 patients yielded a
      total of 10 positive culture results: 1 anal only, 1 vaginal only, and 4 both
      anal and vaginal. This was a positive culture rate of 1.3% overall. The positive
      culture result rates by site were oral 0%, vaginal 1.6%, anal 1.1%, and penile
      0%. The ages of patients with positive culture results ranged from 2 to 13 years;
      all of those with positive culture results were female. DISCUSSION: The incidence
      of positive oral culture results in this sample was zero. This finding supports a
      more limited approach to standard sexually transmitted disease screening in
      pediatric sexual assault victims. The elimination of routine oral cultures in
      pediatric victims without alleged oral contact decreases the examination time,
      decreases the number of invasive procedures associated with the examination, and
      decreases the cost of the examination without negatively affecting patient care.

PMID- 10940839
TI  - The use of unlicensed assistive personnel: an update and skeptical look at a role
      that may present more problems than solutions.
AB  - Patients implicitly rely on nurses to be their advocate. They trust nurses for
      health care information (92%). Approximately three fourths of Americans rated
      nurses' honesty and ethics as either "high" or "very high, placing them above any
      other profession. It is time to reconsider the full implication of Florence
      Nightingale's admonition to do the sick no harm in terms of staffing.

PMID- 10940840
TI  - One emergency department's responses to the increasingly complex challenges of
      patient care at century's change.

PMID- 10940841
TI  - Where are they now? An update on ENA past presidents.

PMID- 10940842
TI  - CEN review questions

PMID- 10940843
TI  - Acute ischemic stroke Emergi-path.

PMID- 10940844
TI  - Clinical nurses forum

PMID- 10940845
TI  - Transport considerations for the pediatric trauma patient.

PMID- 10940847
TI  - From the feds

PMID- 10940846
TI  - Airway management in a patient with penetrating chest trauma: a postflight case
      review.

PMID- 10940848
TI  - "I was born a rambling law": complying with EMTALA when "coming to the emergency
      department" may not mean actually coming to the emergency department.

PMID- 10940849
TI  - Managers forum

PMID- 10940850
TI  - The computer: an educational adjunct.

PMID- 10940851
TI  - Sherlock Holmes and pediatrics.

PMID- 10940852
TI  - Emergency department closures: policy issues.

PMID- 10940853
TI  - Confessions of a former staff nurse.

PMID- 10940854
TI  - ABO incompatible transfusion: what you need to know.

PMID- 10940855
TI  - A sick infant with poor capillary refill.

PMID- 10940856
TI  - Sadie's discharge instructions.

PMID- 10940857
TI  - Modeling Pichia pastoris growth on methanol and optimizing the production of a
      recombinant protein, the heavy-chain fragment C of botulinum neurotoxin, serotype
      A.
AB  - An unstructured growth model for the recombinant methylotrophic yeast P. pastoris
      Mut(+) expressing the heavy-chain fragment C of botulinum neurotoxin serotype A
      [BoNT/A(H(c))], was successfully established in quasi-steady state fed-batch
      fermentations with varying cell densities. The model describes the relationships
      between specific growth rate and methanol concentration, and the relationships
      between specific methanol and ammonium consumption rates and specific growth rate
      under methanol-limited growth conditions. The maximum specific growth rate (mu)
      determined from the model was 0.08 h(-1) at a methanol concentration of 3.65 g/L,
      while the actual maximum mu was 0.0709 h(-1). The maximum specific methanol
      consumption rate was 0.0682 g/g WCW/h. From the model, growth can be defined as
      either methanol-limited or methanol-inhibited and is delineated at a methanol
      concentration of 3.65 g/L. Under inhibited conditions, the observed biomass yield
      (Y(X/MeOH)) was lower and the maintenance coefficient (m(MeOH)) was higher than
      compared to limited methanol conditions. The Y(X/MeOH) decreased and m(MeOH)
      increased with increasing methanol concentration under methanol-inhibited
      conditions. BoNT/A(H(c)) content in cells (alpha) under inhibited growth was
      lower than that under limited growth, and decreased with increasing methanol
      concentration. A maximum alpha of 1.72 mg/g WCW was achieved at a mu of 0.0267 h(
      1) and induction time of 12 h.

PMID- 10940859
TI  - RHIZOSCAN: A semiautomatic image processing system for characterization of the
      morphology and secondary metabolite concentration in hairy root cultures.
AB  - We describe the application of the newly developed RHIZOSCAN software for
      accurate morphological analysis and determination of overall and local secondary
      metabolite concentrations in two clones of Beta vulgaris throughout the growth
      period. Local secondary metabolite concentrations may be determined at any point
      in the root, and pigment gradients in each lateral root can be followed during
      culture and saved to the computer. Throughout the entire analysis process, an
      image appears in a graphical result window on the screen, which enables visual
      evaluation of the numerical output at each stage of the analysis. Biosynthetic
      data on concentrations obtained by image analysis were validated by
      spectrophotometric analysis. The importance of determining appropriate scanning
      and analysis conditions (scanning resolution, background color, threshold value,
      segmentation plane in the hue-saturation-intensity color system and pruning
      length) for obtaining accurate morphological measurements is examined and the
      means of fixing these parameters is described. Our results show that, using
      RHIZOSCAN, detailed and accurate information on root architecture and secondary
      metabolite concentrations can be obtained in a short time.

PMID- 10940858
TI  - Engineering direct fructose production in processed potato tubers by expressing a
      bifunctional alpha-amylase/glucose isomerase gene complex.
AB  - Manipulation of starch biosynthesis/degradation and formation of novel molecules
      in storage organs of plants through genetic engineering is an attractive but
      technically challenging goal. We report here, for the first time, that starch was
      degraded and glucose and fructose were produced directly when crushed potato
      tubers expressing a starch degrading bifunctional gene were heated for 45 minutes
      at 65 degrees C. To achieve this, we have constructed a fusion gene encoding the
      thermostable enzymes: alpha-amylase (Bacillus stearothermophilus) and glucose
      isomerase (Thermus thermophilus). The chimeric gene was placed under the control
      of the granule-bound-starch synthase promoter. This enzymatic complex produced in
      transgenic tubers was only active at high temperature (65 degrees C). More than
      100 independent transgenic potato plants were regenerated. Molecular analyses
      confirmed the stable integration of the chimeric gene into the potato genome. The
      biochemical analyses performed on young and old tubers after high-temperature
      treatment (65 degrees C) revealed an increase in the formation rate of fructose
      and glucose by a factor of 16.4 and 5. 7, respectively, in the transgenic tubers
      as compared to untransformed control tubers. No adverse discernible effect on
      plant development and metabolism including tuber formation and starch
      accumulation was observed in the transgenic plants before heat treatment. Our
      results demonstrate that it is possible to replace starch degradation using
      microbial enzymes via a system where the enzymes are produced directly in the
      plants, but active only at high temperature, thus offering novel and viable
      strategies for starch-processing industries.

PMID- 10940860
TI  - Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO
      produced tissue-type plasminogen activator.
AB  - Human tissue-type plasminogen activator (t-PA) contains a variably occupied
      glycosylation site at Asn-184 in naturally produced t-PA and in t-PA produced in
      recombinant Chinese hamster ovary (CHO) cells. The presence of an oligosaccharide
      at this site has previously been shown to reduce specific activity and fibrin
      binding. In this report, the site occupancy of t-PA is shown to increase
      gradually over the course of batch and fed-batch CHO cultures. Additional cell
      culture factors, including butyrate and temperature, are also shown to influence
      the degree of glycosylation. In each of these cases, conditions with decreased
      growth rate correlate with increased site occupancy. Investigations using
      quinidine and thymidine to manipulate the cell cycle distribution of cultures
      further support this correlation between site occupancy and growth state.
      Comparison of the cell cycle distribution across the range of cell culture
      factors investigated shows a consistent relationship between site occupancy and
      the fraction of cells in the G(0)/G(1) phase of the cell cycle. These results
      support a correlation between growth state and site occupancy, which
      fundamentally differs from site occupancy trends previously observed and
      illustrates the importance of the growth profile of CHO cultures in producing
      consistently glycosylated recombinant glycoproteins.

PMID- 10940861
TI  - The fluid dynamic and shear environment in the NASA/JSC rotating-wall perfused
      vessel bioreactor.
AB  - The rotating-wall perfused-vessel (RWPV) bioreactor, used for both microgravity
      and Earth-based cell science experiments, is characterized in terms of the fluid
      dynamic and fluid shear stress environment. A numerical model of the flow field
      is developed and verified with laser Doppler velocimeter measurements. The
      effects of changes in operating conditions, including rotation rates and fluid
      perfusion rates, are investigated with the numerical model. The operating
      conditions typically used for ground-based experiments (equal rotation of the
      inner and outer cylinders) leads to flow patterns with relatively poor mass
      distribution characteristics. Approximately 50% of the inlet-perfused fluid
      bypasses the bulk of the fluid volume and flows to the perfusion exit. For
      operating conditions typical in microgravity, small differential rotation rates
      between the inner and outer cylinders lead to greatly improved flow distribution
      patterns and very low fluid shear stress levels over a large percentage of the
      fluid volume. Differences in flow patterns for the different operating conditions
      are explored. Large differences in the hydrodynamic environments for operating
      conditions typical of true microgravity and ground-based "microgravity
      simulations" are demonstrated.

PMID- 10940862
TI  - Characterization of an encapsulation device for the production of monodisperse
      alginate beads for cell immobilization.
AB  - An encapsulation device, designed on the basis of the laminar jet break-up
      technique, is characterized for cell immobilization with different types of
      alginate. The principle of operation of the completely sterilizable encapsulator,
      together with techniques for the continuous production of beads from 250 microm
      to 1 mm in diameter, with a size distribution below 5%, at a flow rate of 1-15
      mL/min, is described. A modification of the device, to incorporate an
      electrostatic potential between the alginate droplets and an internal electrode,
      results in enhanced monodispersity with no adverse effects on cell viability. The
      maximum cell loading capacity of the beads strongly depends on the nozzle
      diameter as well as the cells used. For the yeast Phaffia rhodozyma, it is
      possible to generate 700 microm alginate beads with an initial cell concentration
      of 1 x 10(8) cells/mL of alginate whereas only 1 x 10(6) cells/ml could be
      entrapped within 400 microm beads. The alginate beads have been characterized
      with respect to mechanical resistance and size distribution immediately after
      production and as a function of storage conditions. The beads remain stable in
      the presence of acetic acid, hydrochloric acid, water, basic water, and sodium
      ions. The latter stability applies when the ratio of sodium: calcium ions is less
      than 1/5. Complexing agents such as sodium citrate result in the rapid
      solubilization of the beads due to calcium removal. The presence of cells does
      not affect the mechanical resistance of the beads. Finally, the mechanical
      resistance of alginate beads can be doubled by treatment with 5-10 kDa chitosan,
      resulting in reduced leaching of cells.

PMID- 10940863
TI  - Applicability of two-step models in estimating nitrification kinetics from batch
      respirograms under different relative dynamics of ammonia and nitrite oxidation.
AB  - A mechanistically based nitrification model was formulated to facilitate
      determination of both NH(4)(+)-N to NO(2)(-)-N and NO(2)(-)-N to NO(3)(-)-N
      oxidation kinetics from a single NH(4)(+)-N to NO(3)(-)-N batch-oxidation profile
      by explicitly considering the kinetics of each oxidation step. The developed
      model incorporated a novel convention for expressing the concentrations of
      nitrogen species in terms of their nitrogenous oxygen demand (NOD).
      Stoichiometric coefficients relating nitrogen removal, oxygen uptake, and biomass
      synthesis were derived from an electron-balanced equation.%A parameter
      identifiability analysis of the developed two-step model revealed a decrease in
      correlation and an increase in the precision of the kinetic parameter estimates
      when NO(2)(-)-N oxidation kinetics became increasingly rate-limiting. These
      findings demonstrate that two-step models describe nitrification kinetics
      adequately only when NH(4)(+)-N to NO(3)(-)-N oxidation profiles contain
      sufficient information pertaining to both nitrification steps. Thus, the rate
      determining step in overall nitrification must be identified before applying
      conventionally used models to describe batch nitrification respirograms.

PMID- 10940864
TI  - Feasible boundaries of aqueous two-phase systems with NH(3) and CO(2) as
      recyclable volatile salts.
AB  - Aqueous two-phase systems (ATPSs) have great potential for use in the downstream
      processing of fermentation products. A major drawback of these systems, limiting
      application in industrial practice up till now, is the consumption of large
      amounts of auxiliary materials such as polymers and salts. Making use of
      alternative auxiliaries can diminish this relatively large discharge. A possible
      approach is to make use of volatile salts induced by combinations of ammonia and
      carbon dioxide that can be recycled to the extraction system. As part of an
      ongoing research effort on ATPSs with volatile salts, this work aims at getting
      more information on the system boundaries or operating conditions of these
      systems in terms of phase behavior. The results show that the NH(3)/CO(2) ratio
      is an important parameter that has a large influence on the system boundaries.
      Both for systems with PEG 2000 and PEG 4000, this ratio has to be larger than
      about 1.75 to make a liquid-liquid phase separation possible. The most optimal
      ratio seems to be 2.0 for reasons of solution composition and absence of solid
      salt.

PMID- 10940865
TI  - New system for preparative electrochromatography of proteins.
AB  - Electrochromatography employs an axial electric field across a chromatographic
      stationary phase to separate proteins and other molecules based on differences in
      electrophoretic mobility. Because the separation is electrically driven, the need
      for additional chemical reagents is reduced. Two major impediments to scale-up of
      electrochromatography columns, removal of heat and electrolysis gases, have
      historically limited the diameter of packed columns to 2.5 cm ID with volumes of
      approximately 55 mL. We report a novel electrochromatography column that
      effectively removes electrolysis gases and minimizes heating. A vital component
      of this system is a new electrode design that couples a platinum gauze with an
      ultrafiltration membrane across both ends of the column. Use of a methacrylate
      base stationary phase enabled axial voltage gradients of 10 to 20 V/cm.
      Thermocouples inserted radially in the column at four axial positions showed that
      the flow of a 4 degrees C mobile phase coupled with heat conduction through the
      column walls controlled the temperature to 28 degrees C. The new column design,
      with dimensions of 3.81 cm ID x 38.1 cm long and bed volume of 400 mL, was
      demonstrated by separating mixtures of BSA and myoglobin. The column was operated
      in a horizontal position with radial sample injection and withdrawal at the ends
      of the packed bed. These experiments are a first step in demonstrating that scale
      up of electrochromatography columns can be achieved by choosing appropriate flow
      rates, voltage gradients, and stationary phase.

PMID- 10940866
TI  - Metabolism of citric acid production by Aspergillus niger: model definition,
      steady-state analysis and constrained optimization of citric acid production
      rate.
AB  - In an attempt to provide a rational basis for the optimization of citric acid
      production by A. niger, we developed a mathematical model of the metabolism of
      this filamentous fungus when in conditions of citric acid accumulation. The
      present model is based in a previous one, but extended with the inclusion of new
      metabolic processes and updated with currently available kinetic data. Among the
      different alternatives to represent the system behavior we have chosen the S
      system representation within power-law formalism. This type of representation
      allows us to verify not only the ability of the model to exhibit a stable steady
      state of the integrated system but also the robustness and quality of the
      representation. The model analysis is shown to be self-consistent, with a stable
      steady state, and in good agreement with experimental evidence. Moreover, the
      model representation is sufficiently robust, as indicated by sensitivity and
      steady-state and dynamic analyses. From the steady-state results we concluded
      that the range of accuracy of the S-system representation is wide enough to model
      realistic deviations from the nominal steady state. The dynamic analysis
      indicated a reasonable response time, which provided further indication that the
      model is adequate. The extensive assessment of the reliability and quality of the
      model put us in a position to address questions of optimization of the system
      with respect to increased citrate production. We carried out the constrained
      optimization of A. niger metabolism with the goal of predicting an enzyme
      activity profile yielding the maximum rate of citrate production, while, at the
      same time, keeping all enzyme activities within predetermined, physiologically
      acceptable ranges. The optimization is based on a method described and tested
      elsewhere that utilizes the fact that the S-system representation of a metabolic
      system becomes linear at steady state, which allows application of linear
      programming techniques. Our results show that: (i) while the present profile of
      enzyme activities in A. niger at idiophase steady state yields high rates of
      citric acid production, it still leaves room for changes and suggests possible
      optimization of the activity profile to over five times the basal rate synthesis;
      (ii) when the total enzyme concentration is allowed to double its basal value,
      the citric acid production rate can be increased by more than 12-fold, and even
      larger values can be attained if the total enzyme concentration is allowed to
      increase even more (up to 50-fold when the total enzyme concentration may rise up
      to 10-fold the basal value); and (iii) the systematic search of the best
      combination of subsets of enzymes shows that, under all conditions assayed, a
      minimum of 13 enzymes need be modified if significant increases in citric acid
      are to be obtained. This implies that improvements by single enzyme modulation
      are unlikely, which is in agreement with the findings of some investigators in
      this and other fields.

PMID- 10940867
TI  - Effect of initial carbon sources on the performance of microbial fuel cells
      containing Proteus vulgaris.
AB  - Mediator-coupled microbial fuel cells containing Proteus vulgaris were
      constructed and the cell performance was tested. Fuel cell efficiency depended on
      the carbon source in the initial medium of the microorganism. Maltose and
      trehalose were not utilized substantially by P. vulgaris; however, their presence
      in the initial medium resulted in enhanced cell performance. In particular,
      galactose showed 63% coulombic efficiency in a biofuel cell after P. vulgaris was
      cultured in a trehalose-containing medium. This work demonstrates that optimum
      utilization of carbon sources by microorganisms, which leads to the maximization
      of fuel cell performance, is possible simply by adjusting initial carbon sources.

PMID- 10940868
TI  - CCR2+ and CCR5+ CD8+ T cells increase during viral infection and migrate to sites
      of infection.
AB  - Chemokines and their receptors play a critical role in the selective recruitment
      of various leukocyte subsets. In this study, we correlated the expression of
      multiple chemokine and CC chemokine receptor (CCR) genes during the course of
      intracerebral (i.c.) infection with lymphocytic choriomeningitis virus (LCMV) and
      vesicular stomatitis virus (VSV), which are prototypic of a noncytopathic and a
      cytopathic virus, respectively. Infection of mice with either virus resulted in
      rapid activation and overlapping cerebral expression of a number of chemokine
      genes. Infection with VSV i.c. causes a rapidly lethal, T cell-independent
      encephalitis, and infection resulted in a dramatic early up-regulation of
      chemokine gene expression. Similar marked up-regulation of chemokine expression
      was not seen until late after LCMV infection and required the presence of
      activated T cells. Cerebral CCR gene expression was dominated by CCR1, CCR2 and
      CCR5. However, despite a stronger initial chemokine signal in VSV-infected mice,
      only LCMV-induced T cell-dependent inflammation was found to be associated with
      substantially increased expression of CCR genes. Virus-activated CD8+ T cells
      were found to express CCR2 and CCR5, whereas activated monocytes/macrophages
      expressed CCR1 in addition to CCR2 and CCR5. Together, these CCR profiles readily
      account for the CCR profile prominent during CD8+-dependent CNS inflammation.

PMID- 10940869
TI  - The effect of calcineurin inhibitors and corticosteroids on the differentiation
      of human dendritic cells.
AB  - Corticosteroids and the calcineurin inhibitors cyclosporin A (CsA) and FK506 have
      been studied extensively regarding their effects on T lymphocytes, but their
      effects on dendritic cells (DC) are relatively unknown. Monocytes are one of the
      precursors of DC that differentiate into CD14-CD1a+ immature DC upon culture with
      IL-4 and GM-CSF. The presence of CsA or FK506 during differentiation did not
      affect DC development. In contrast, the presence of corticosteroids, either
      dexamethasone (Dex) or prednisolone (Pred), for as little as the first 48 h of
      culture blocked the generation of immature DC. Dex-DC were unresponsive to
      signals inducing maturation (CD40 ligand, lipopolysaccharide), as demonstrated by
      the absence of CD83, CD80/CD86 and HLA-DR up-regulation and their strongly
      reduced T cell stimulatory capacity. Furthermore, Dex-DC showed a decreased CD40
      ligand-induced IL-6 and TNF-alpha production, a complete block in IL-12p40
      production, while IL-10 production was unaffected. CsA-DC and FK506-DC showed a
      partial reduction in the production of TNF-alpha, whereas all other functional
      activities appeared to be similar to control DC. These data show that, when
      compared to calcineurin inhibitors, corticosteroids have a unique and profound
      inhibitory effect on the generation and function of DC.

PMID- 10940870
TI  - Immature dendritic cells generated with low doses of GM-CSF in the absence of IL
      4 are maturation resistant and prolong allograft survival in vivo.
AB  - Dendritic cells (DC) were cultured from mouse bone marrow (BM) progenitors in low
      concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF)
      (GM(lo) DC) by two different protocols. The phenotype and functional properties
      of these GM(lo) DC were compared to those of standard BM-DC cultures generated in
      high concentrations of GM-CSF (GM(hi) DC) or in low GM-CSF plus IL-4 (GM(lo)/IL-4
      DC). An effect of IL-4 on maturation was observed only at low but not high doses
      of GM-CSF. Compared to mature DC, GM(lo) DC were phenotypically immature, weak
      stimulators of allogeneic and peptide-specific T cell responses, but
      substantially more potent in presentation of native protein. Immature GM(lo) DC
      were resistant to maturation by lipopolysaccharide, TNF-alpha or anti-CD40
      monoclonal antibodies, as the expression of co-stimulatory molecules was not
      increased, and stimulatory activity in oxidative mitogenesis was not enhanced.
      These maturation-resistant immature GM(lo) DC induced T cell unresponsiveness in
      vitro and in vivo. GM(lo) DC also prolonged haplotype-specific cardiac allograft
      survival (from 8 days to >100 days median survival time) when they were
      administered 7 days (but not 3, 14 or 28 days) before transplantation. Our
      findings may have important implications for future studies in T cell tolerance
      induction in vivo.

PMID- 10940871
TI  - Functionally distinct CD8+ memory T cell subsets in persistent EBV infection are
      differentiated by migratory receptor expression.
AB  - Human memory T lymphocytes have recently been re-defined as central or effector
      memory cells (Sallusto, F., Lenig, D., Forster, R., Lipp, M. and Lanzavecchia,
      A., Nature 1999. 401: 708-712). Effector memory cells (T(em)) are targeted to the
      peripheral tissues and show rapid effector function in response to antigenic
      stimulation. Central memory (T(cm)) cells are targeted to the lymph nodes and
      cannot be immediately activated. In this report HLA-A2-Epstein-Barr virus (EBV)
      peptide tetramers have been used to characterize the EBV-specific CD8+ T cell
      subsets in persistent EBV infection. In short-term activation studies two
      populations of tetramer-positive T cells were identified. One group resembled
      T(em) cells in that they rapidly produced IFN-gamma and lacked the lymph node
      homing receptor, CD62L, the second was similar to T(cm) cells since they were
      CD62L+ but could not be immediately induced to express IFN-gamma.

PMID- 10940872
TI  - Pregnancy specific glycoprotein 18 induces IL-10 expression in murine
      macrophages.
AB  - Pregnancy specific glycoproteins (PSG) are secreted into the maternal circulation
      and may function to regulate the immune system to ensure survival of the fetal
      allograft. In this study, we have cloned and determined by in situ hybridization
      the placental sites of expression of Psg18, a murine member of the PSG family
      that belongs to the Ig superfamily. Recombinant PSG18 and a truncated form
      containing only the N-terminal domain (PSG18N) were used to treat peritoneal
      elicited macrophages and RAW 264.7 cells. PSG18 and PSG18N induced IL-10 mRNA
      expression in the presence and absence of lipopolysaccharide (LPS). IL-10 protein
      was also detected in the supernatant of macrophages and RAW 264.7 cells following
      PSG18N treatment, albeit higher concentrations were required in the absence of
      LPS. In contrast, treatment of these cells with PSG18N resulted in no change in
      the expression of IL-1/beta, TNF-alpha, inducible NO synthase, IL-12p40 and TGF
      beta mRNA. Taken together, these results suggest that PSG18 selectively up
      regulates IL-10 production by macrophages, providing a possible mechanism by
      which this protein helps promote successful pregnancy.

PMID- 10940873
TI  - Systemic or mucosal administration of immunostimulatory DNA inhibits early and
      late phases of murine allergic conjunctivitis.
AB  - Seasonal allergic conjunctivitis is one of the most common manifestations of
      allergic disease, affecting 15 % population in the United States annually. Short
      ragweed (RW) is a major cause of seasonal allergies. Immunostimulatory DNA
      sequences (ISS or CpG motifs) can inhibit an on-going Th2/allergic response and
      induce a de novo Th1 response. In this study, we investigated the ability of
      these ISS to modulate allergic responses in a RW-induced mouse model of seasonal
      allergic conjunctivitis. Systemic or mucosal administration of ISS
      oligonucleotide (ISS-ODN) after RW sensitization inhibited both the immediate
      hypersensitivity response and the late-phase cellular infiltration and induced a
      RW-specific Th1 response. ISS-ODN administration suppressed the rise of RW
      specific IgE titers after repeated allergen challenge. Furthermore, ISS
      administration was more effective than dexamethasone in inhibiting the allergic
      response. Mechanistically, the ISS-induced immunomodulatory effects were
      abolished when mice were treated with anti-IL-12 neutralizing antibodies,
      suggesting a pivotal role for type 1 cytokines in the inhibition of both the
      immediate hypersensitivity and the late-phase cellular infiltration. Thus, ISS
      ODN is a novel anti-inflammatory and immunomodulatory agent that significantly
      inhibits the allergic response and may provide an alternative to the current
      standard care of ocular allergy.

PMID- 10940874
TI  - Antigen receptor signal transduction: activating and inhibitory antigen receptors
      regulate STAT1 serine phosphorylation.
AB  - Antigen receptors are crucial regulators of the mammalian immune response.
      Immediate antigen receptor proximal signal transduction pathways mediated by
      tyrosine (Tyr) kinases are well defined. In contrast, much less is known about
      the network of serine (Ser) kinases and Ser kinase substrates that are linked to
      antigen receptor function. Here we describe a new signaling module for antigen
      receptors in lymphocytes; a Ser kinase pathway that phosphorylates Ser 727 in
      STAT1alpha, a member of the signal transducer and activator of transcription gene
      family. In the present study we have explored the regulation of STAT1 Ser 727
      phosphorylation in human T and B lymphocytes and show that it is controlled by
      both positive and negative antigen receptor signaling cascades. Ligation of
      antigen receptors in both B and T cells induce a delayed but then sustained
      phosphorylation of STAT1 on Ser 727. STAT1 Ser phosphorylation is induced by the
      TCR in the absence of STAT1 Tyr phosphorylation, indicating that in T cells STAT1
      Ser and Tyr phosphorylation are independent events. Antigen receptor regulation
      of STAT Ser phosphorylation is dependent on phosphatidylinositol 3-kinase
      mediated signals. Furthermore, the negative regulatory receptor FcgammaRIIb,
      which mediates vital feedback control of B cell responses, prevents antigen
      receptor-induced phosphorylation of STAT1 Ser 727. The ability of antigen
      receptors to both positively and negatively regulate STAT1 Ser 727
      phosphorylation reveals a Ser kinase network that operated during sustained
      responses to antigen receptor engagement.

PMID- 10940876
TI  - CD14+CD16++ cells derived in vitro from peripheral blood monocytes exhibit
      phenotypic and functional dendritic cell-like characteristics.
AB  - We previously reported an increased percentage of CD14+CD16++ monocytes in the
      peripheral blood of HIV-infected patients but the physiopathological role of this
      monocyte subset remains unclear. Cells with a CD14+CD16++ phenotype may be
      obtained in vitro by culturing human peripheral blood monocytes in the presence
      of GM-CSF, IL-4 and IL-10. In the present study, we compared the phenotypic and
      functional characteristics of monocytes-derived CD14+CD16++ cells with those of
      macrophages and dendritic cells. We show that the CD14+CD16++ cells express
      dendritic cell markers: CD40, CD80, CD86, HLA-DR, CD11b, CD11c, CD18, CD1a, and
      CD83. Using RNase protection assay, we demonstrate that CD14+CD16++ cell subset
      expresses a low ratio of IL-1beta/IL-1ra mRNA and expresses IL-6, MIP-1alpha, MIP
      1beta, MCP-1, IL-8, RANTES and I-309 transcripts, similar to dendritic cells.
      CD14+CD16++ cells produce IL-12, MCP-1 and IL-8, as assessed by flow cytometry.
      Moreover, CD14+CD16++ cells pulsed with different recall antigens induce a potent
      autologous T cell proliferation. Altogether, these results provide evidence that
      CD14+CD16++ cells differentiated in vitro from peripheral blood monocytes exhibit
      dendritic cell characteristics.

PMID- 10940875
TI  - CD19-deficient mice exhibit poor responsiveness to oral immunization despite
      evidence of unaltered total IgA levels, germinal centers and IgA-isotype
      switching in Peyer's patches.
AB  - CD19 exhibits a critical role as a response regulator in B cells, influencing
      activation, differentiation and survival. Accordingly, CD19-deficient mice
      largely lack B-1 cells, and their conventional B-2 cells are poor responders to
      thymus-dependent antigen. Since both B-1 and B-2 cells may contribute to the
      total intestinal IgA production, we investigated whether lack of CD19 negatively
      affected mucosal immunity. We found that CD19(-/-) mice have near normal total
      IgA levels in serum and gut mucosa and, contrary to systemic lymphoid tissues,
      Peyer's patches (PP) had germinal centers to which also IgA+ B cells localized.
      However, the mice demonstrated severely impaired responses to oral immunization
      with keyhole limpet hemocyanin plus cholera toxin adjuvant. Mucosal responses to
      oral immunization were significantly more impaired than systemic responses.
      Despite normal specific IL-4 production, a selective defect in Th2-regulated B
      cell isotypes was observed, with poor or no mucosal IgA, low serum IgG1 and no
      IgE, but intact serum IgA and IgG2a production. Ex vivo experiments revealed
      strongly inhibited CD40-stimulated proliferation and IgA differentiation in CD19
      deficient PP B cells. Taken together, an impaired CD40 responsiveness selectively
      affected Th2, but not Th1, coordinated B cell responses. The CD19(-/-) mice
      provide compelling evidence for the differential regulation of serum and mucosal
      IgA immunity.

PMID- 10940877
TI  - RNA and protein expression of the murine autoimmune regulator gene (Aire) in
      normal, RelB-deficient and in NOD mouse.
AB  - Mutations in the putative transcription factor autoimmune regulator (AIRE) gene
      are responsible for autoimmune polyendocrinopathy-candidiosis-ectodermal
      dystrophy (APECED; OMIM#240300), a monogenic recessively inherited disease
      characterized by destructive autoimmune diseases of the endocrine organs, chronic
      candidiosis of mucous membranes and ectodermal dystrophies. In this study the
      expression of murine homolog for AIRE protein, Aire, was detected in a fraction
      of thymic medullary epithelial cells. Subcellularly, in thymus the protein
      appears as concentrated into nuclear dot-like structures, whereas in transfected
      cells the protein is also bound along a cytosolic fibrillar network. By RT-PCR
      Aire mRNA was detected in thymus, lymph node, spleen and testis although the
      second round PCR amplified Aire specific band from most mouse tissues analyzed.
      Furthermore, the Aire mRNA was detected in dendritic cell (DC) populations
      isolated from thymus and spleen, representing both myeloid- and lymphoid-related
      lineages of DC. We also demonstrate that the Aire protein is absent in the thymus
      of RelB-deficient mouse and in NOD thymus most of the Aire positive cells showed
      an abnormal morphology. These results suggest that the Aire protein is associated
      with the normal development and/or action of a subset of thymic medullary stromal
      cells involved in tolerance induction.

PMID- 10940878
TI  - In vivo reduction of telomere length in human antigen-reactive memory T cells.
AB  - There is a reduction in the average telomere lengths of CD4+ "memory" T cells,
      defined by the CD45RO+ phenotype, compared to CD54RA+ "naive" T cells. However,
      other studies suggest that telomerase activity often is sufficient to maintain
      the telomere length of certain B and T cell populations following immune
      activation in vivo. Thus it is uncertain whether genuine memory CD4+ T cells,
      defined by an immune response to specific recall antigens, would display
      telomeres of reduced length, or whether telomere size would be maintained.
      Therefore, we examined the telomere lengths of T cells responding to two common
      recall antigens, tetanus toxoid and Candida albicans. Telomere terminal
      restriction fragment length was assessed by Southern blots or by flow cytometry
      following in situ hybridization with telomere-specific peptide nucleic acid
      probes. For the five subjects tested, the Candida- or tetanus-reactive memory T
      cell populations demonstrated a significant reduction of telomere length even
      when compared to the phenotypically defined memory CD45RO+ T cell populations
      isolated from peripheral blood mononuclear cells. This finding suggests that
      telomerase activity does not fully compensate for the effects of in vivo
      activation and proliferation of some antigen-specific CD4+ T cell populations.
      This may contribute to immune senescence.